PMID- 25110536 TI - Effect of sitagliptin on lipid profile in patients with type 2 diabetes mellitus. AB - BACKGROUND: Animal studies have demonstrated that an inhibition of DPP-4 has an impact on the secretion of cholesterol and apoB by the small intestine. However, there is no consensus about the changes of the lipid profile following administration of sitagliptin. METHODS: Accordingly, we treated patients who had type 2 diabetes complicated by dyslipidemia with sitagliptin and evaluated its effects on the profile of lipid parameters. A total of 248 outpatients with type 2 diabetes complicated by dyslipidemia were treated with sitagliptin at a daily dose of 50 mg. The levels and percent changes of lipid and glucose metabolism markers were measured at baseline and at 12 weeks after the initiation of treatment. RESULTS: Both plasma glucose and HbA1c were significantly decreased. Among the lipid parameters, total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) showed a significant decrease (TC 3.6+/ 15.6%, non-HDL-C 2.9+/-19.7%; P < 0.05). Stratified analysis revealed a significant decrease of TC, low-density lipoprotein cholesterol (LDL-C) and non HDL-C in the high triglyceride (TG) group (>= 150 mg/dL) (P < 0.05). Analysis stratified by demographic factors demonstrated significant differences in the changes of TC, LDL-C and non-HDL-C. Multivariate analysis showed a significant decrease of the TC, LDL-C and non-HDL-C levels in the high TG group (>= 150 mg/dL), as well as a significant decrease of TC and LDL-C in patients using strong statins. CONCLUSIONS: The results suggested that sitagliptin caused a significant decrease of TC, LDL-C and non-HDL-C, particularly in patients with high baseline TG levels and those using strong statins. PMID- 25110537 TI - Psychological distress, personality traits and functional disability in patients with osteonecrosis of the femoral head. AB - BACKGROUND: The aim of the present study was to investigate personality traits, psychological distress and functional disability in patients with non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: Sixty-seven patients participated in the study, 48 males and 19 females. The mean age was 37.6 years (SD: 10.92, range: 15 - 61). Seventy-five healthy individuals, age and sex matched, served as controls. Socio-demographic information and clinical data were collected. The following instruments were used: the General Health Questionnaire (GHQ-28), the Defence Style Questionnaire (DSQ) and the World Health Organization Disability Assessment Schedule II (WHO-DAS II). RESULTS: Patients suffering from ONFH presented higher scores at the GHQ-28 compared to healthy controls (P < 0.001). Duration of disease (P < 0.047) and age (P < 0.023) were the main factors associated with psychological distress (P < 0.003). Personality traits such as image distorting (P < 0.025) and self-sacrificing (P < 0.029) were identified in patients with ONFH compared to healthy controls. Functional disability was associated with high scores at GHQ-28 scale (P < 0.001). The "adaptive personality structure", as measured by DSQ was negatively associated with functional impairment (P < 0.022). CONCLUSIONS: Patients with ONFH more commonly present symptoms of psychological distress associated with distinct functional clinical parameters. The present study also reveals the role of personality traits. Further investigation could specify the possible influence of psychopathology and personality traits or coping strategies on the course of disease. PMID- 25110538 TI - Risk factors for subclavian vein thrombosis in cancer patients with total parenteral nutrition. AB - BACKGROUND: There are few reports on total parenteral nutrition (TPN) and its possible prothrombotic effect. The purpose of this study was to identify risk factors for subclavian vein thrombosis (SVT) in patients receiving TPN. METHOD: Cancer patients with indwelling subclavian catheters and TPN were followed in a cohort study. Doppler ultrasound examination was performed 8 and 30 days after catheter placement. RESULTS: One hundred twenty-one patients were included, with a mean of 61 (+/- 11.8) years of age. We detected 36 SVT events at day 8 (29.8%) and 47 (38.8%) at day 30 after central catheter placement. Mean length of subclavian catheterization was 17.2 (+/- 8.2) days. Fifty-three point three percent of patients receiving >= 3,050 mOsm TPN in 24 hours developed SVT (relative risk (RR) = 2.01, 95% CI, 1.14 - 3.57; P = 0.016) at day 8 and 60% (RR = 1.67, 95% CI, 1.30 - 2.71; P = 0.038) at day 30 post-catheter placement. Protein administration of > 97.5 g/day was shown to be a risk factor for early thrombosis with a mean of 16.88 days for the development of SVT (95% CI, 10 - 23.7) versus 27.8 days (95% CI, 25.8 - 29.9) in the group with nutritional protein content < 97.5 g/day (P = 0.000). CONCLUSION: High-osmolarity and high protein nutrition formulas were shown to be risk factors for SVT in cancer patients receiving TPN. PMID- 25110539 TI - Effect of statins on endothelial function in patients with acute coronary syndrome: a prospective study using adhesion molecules and flow-mediated dilatation. AB - BACKGROUND: Accumulating evidence suggests that inflammatory mechanisms play a central role in the development, progression and outcome of atherosclerosis. Recent evidence suggests that statins improve anti-inflammatory, anti-thrombotic and endothelial functions, along with their lipid-decreasing effects. We examined the effect of statins on endothelial function using biochemical markers of endothelial dysfunction and brachial artery flow-mediated dilatation (FMD). METHODS: Thirty male patients presenting with acute coronary syndrome (ACS) and 26 age-matched healthy control subjects aged 40 - 60 years who were not on any medication were enrolled in the study. The patient group was started on atorvastatin (40 mg/day) without consideration of their low-density lipoprotein (LDL)-cholesterol levels. Endothelin, sICAM and E-selectin from stored serum samples were measured using commercially available enzyme-linked immunosorbant assays (ELISAs). Endothelial function was assessed using brachial artery FMD. RESULTS: Prior to statin treatment, E-selectin, sICAM and endothelin levels, endothelial dysfunction markers, were 99.74 +/- 34.67 ng/mL, 568.8 +/- 149.0 ng/mL and 0.62 +/- 0.33 fmol/mL, respectively in the patient group. E-selectin and sICAM levels were significantly higher in the patients than in the control subjects (P < 0.001); however, endothelin levels were not significantly different between groups. Statin treatment significantly reduced E-selectin and sICAM levels (P < 0.001); however, the decrease in endothelin levels was not statistically significant. %FMD values were significantly increased after statin treatment (P = 0.005), and levels of C-reactive protein (CRP), an inflammation marker, were significantly reduced. CONCLUSION: Our results indicate that statins play an important role in treatment endothelial dysfunction by reducing adhesion of inflammatory cells. PMID- 25110540 TI - Quality of life of patients after an acute coronary event: hospital discharge. AB - BACKGROUND: The acute coronary syndrome (ACS) has a high morbi-mortality rate, including physical deficiencies and functional limitations with impact on quality of life. Cardiovascular rehabilitation 1 (CVR1) should begin as early as possible, to enable improvement in functional capacity and quality of life. Previous studies have shown association of cardiovascular diseases with quality of life, in which depression and anxiety are the domains most altered. The aim of the study is to verify the impact of an acute coronary event on quality of life at the moment of hospital discharge. METHODOLOGY: This was a cross-sectional study, with ACS patients hospitalized in ICU of a private hospital in the city of Salvador, Brazil, submitted to CVR1. The quality of life questionnaire Euroqol-5D was applied on discharge from hospital. Patients included in the study were those with ACV, who had medical permission to walk, had not been submitted to acute surgical treatment, were time and space oriented, and over the age of 18 years. Patients excluded from the study were those with cognitive, orthopedic and neurological problems, who used orthesis on a lower limb, and were in any condition of risk at the time of beginning with CVR1. Data were collected by a previously trained ICU team. RESULTS: Data were collected of 63 patients who revealed compromise in the domains of pain/feeling ill (20.63%) and anxiety/depression (38.09%). Statistical significance was observed in the association between sex and pain/feeling ill (P < 0.01), sex and anxiety/depression (P < 0.01), diabetes and mobility (P < 0.01), hereditary factors and anxiety/depression (p < 0.01), BMI and pain/feeling ill (P < 0.01). CONCLUSION: In this sample of patients, on discharge from hospital after ACS, the pain/feeling ill and anxiety/depression domains were shown to be compromised. PMID- 25110541 TI - Accuracy of unstimulated Basal serum thyroglobulin levels in assessing the completeness of thyroidectomy. AB - BACKGROUND: Complete excision is important for proper surgical treatment of thyroid disorders. Functional thyroid tissue can be identified based on the level of serum thyroglobulin (Tg), which is produced only by the thyroid follicular cells, and nuclear scan. METHODS: Serum thyroid stimulating hormone (TSH), free thyroxin (FT4), basal (unstimulated) Tg and anti-Tg antibody (anti-Tg ab) were measured at the sixth postoperative month in 100 patients with benign thyroid disorders treated by total thyroidectomy. Thyroid nuclear scan was obtained to identify functional remnant of the thyroid gland. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the Tg levels in assessing thyroid remnant were calculated. RESULTS: Positive scan showed thyroid remnant in 23 patients, among whom 16 were Tg positive (true positive) and seven were Tg negative (< 0.5 ng/mL) (false negative). In these patients, the nuclear scan revealed pyramidal lobe remnants. In 77 patients with negative scan, the Tg levels were also negative (true negative), and the PPV, NPV, sensitivity, specificity and accuracy of the Tg levels were 100%, 92%, 70%, 100% and 93%, respectively. CONCLUSIONS: The positive basal Tg (> 0.5 ng/mL) level accurately indicated the functional thyroid remnant after total thyroidectomy. The negative Tg (< 0.5 ng/mL) level supported complete excision of the thyroid gland. The surgical completeness of total thyroidectomy was accurately evaluated based on the serum Tg levels. Therefore, serum Tg levels should be measured in postoperative follow-up to determine the completeness of total thyroidectomy. PMID- 25110542 TI - Validation of the edinburgh postpartum depression scale in a population of adult pregnant women in Mexico. AB - BACKGROUND: The Edinburgh postnatal depression scale (EPDS) is useful for screening depression in puerperal women as well as women during pregnancy. However, such instrument should be validated in a given language before it can be used. There is not validated Mexican version of the EPDS for use in adult pregnant women. Therefore, we sought to validate a Spanish translated Mexican version of the EPDS in a population of adult pregnant women. METHODS: One hundred fifty-eight adult women (mean age: 28 +/- 6.8 years; range: 18 - 45 years) within their 2 - 9 months of pregnancy attending routine prenatal consultations in a public hospital in Durango City, Mexico were studied. All pregnant women submitted a Spanish translated Mexican version of the EPDS. In addition, participants were assessed for major and minor depression by using the DSM-IV criteria. RESULTS: Of the 158 pregnant women studied, 11 had major depression and 26 had minor depression by the DSM-IV criteria. The best EPDS score for screening combined major and minor depression in adult pregnant women was 9/10. This threshold showed a sensitivity of 75.7%, a specificity of 74.4%, a positive predictive value of 50.8%, a negative predictive value of 94.7% and an area under the curve of 0.89 (95% confidence interval: 0.71 - 1.06). CONCLUSION: The Mexican version of the EPDS can be considered for screening depression in Mexican adult pregnant women whenever a cut-off score of 9/10 is used. PMID- 25110543 TI - Chronic subdural hematoma in patients over 90 years old in a super-aged society. AB - BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common diseases in neurosurgical practice, particularly among aged patients. With the continuing increase in the aged population, further increases in incidence are expected. However, few studies have focused on CSDH in super-aged patients over 90 years old. METHODS: We retrospectively reviewed medical records for 20 consecutive patients over 90 years old with CSDH treated in our department between 2007 and 2013. The diagnosis of CSDH was confirmed by computed tomography (CT). Patients were divided into a surgery group and a conservative group. Surgical procedures included burr-hole surgery followed by insertion of a subdural drain under local anesthesia. Clinical data were compared and analyzed. Neurological status was evaluated according to the modified Rankin Scale at three time points: before suffering from CSDH; at the time of referral or admission to our department; and at discharge or 1 month after the first referral. Statistical tests were used to analyze data and values of P < 0.05 were considered significant. RESULTS: Mean age for the 20 cases was 92.6 years (range, 90 - 96 years). The leading symptoms in this population were hemiparesis and gait disturbance, followed by disturbance of consciousness and speech disturbance. Twelve patients underwent burr-hole surgery. Mean maximum thickness of subdural hematoma as measured on CT was significantly higher in the surgery group (28.2 +/- 5.4 mm) than in the conservative group (17.0 +/- 3.8 mm; P < 0.01). Postoperatively, mean neurological status was significantly improved in the surgery group (P < 0.01). After surgery, 66.7% of patients could return home directly from hospital. No significant perioperative complications directly related to surgery were encountered in the surgery group, except for transient postoperative restlessness and bruising of extremities due to falls. CONCLUSIONS: Surgery for CSDH is safe and positively recommended even in super-aged patients over 90 years old if the patient's physical status is fair. Pre-illness status is the most important factor for considering operative indications and represents a limiting factor for postoperative outcomes in this age population. PMID- 25110544 TI - Does modification to the approach to contacting potential participants improve recruitment to clinical trials? AB - BACKGROUND: It is critical that clinical trial researchers ensure efficient and successful patient recruitment. Recruitment is often slower than expected and required sample sizes not obtained within initial funding deadlines. There is little rigorous evidence supporting ways to improve recruitment. We hypothesized making telephone contact with subjects prior to hospital attendance would improve recruitment rates into clinical trials. METHODS: Retrospective post hoc analysis of recruitment rates in an on-going clinical trial was undertaken. Two hundred twelve consecutive patients were recruited over 6 months. During the first 3 months, patients received a telephone call from the research team and also received an information sheet by post prior to clinic attendance (group 1). The study was discussed on telephone and any issues were re-addressed at the patient's clinic appointment when they were formally invited to participate in the study. After 3 months, the investigators stopped telephoning the patients (group 2); patients were invited to participate in the study by post and were first spoken to directly by an investigator in clinic. The study protocol and investigators did not change between groups. RESULTS: There was no significant difference in baseline demographics between the two groups. There was a significant improvement in recruitment rate in group 1 compared to group 2 (77.7% vs. 45.0%, P < 0.0001). An improvement in clinic attendance rate in group 1 was observed, although this was not significant (did not attend rate: 2.9% vs. 7.8%, P = 0.14). CONCLUSION: Telephone contact between researchers and potential participants prior to clinic attendance can greatly improve study recruitment rates. This information may benefit the design of all clinical studies. PMID- 25110545 TI - Recurrent arterial and venous thromboemboli as initial presentation of acute promyelocytic leukemia. AB - We report a case of a 52-year-old Caucasian woman diagnosed with a synchronic arterial and venous thrombosis as an initial presentation of an acute promyelocytic leukemia (APL). After the diagnosis, the patient was treated with all trans-retinoic acid and arsenic chemotherapy concomitant to systemic anticoagulation. This treatment regimen led to a complete remission and absence of relapse of the thrombosis or APL during the follow-up. To our knowledge, this presentation is the second case in the literature. We use this opportunity to emphasize the importance of performing a complete medical evaluation in cases of unusual thromboembolic events. PMID- 25110546 TI - Potential biomarker for human uterine leiomyosarcoma. PMID- 25110547 TI - Secondary polycythemia and the risk of venous thromboembolism. PMID- 25110548 TI - Behavioral Attention: A Longitudinal Study of Whether and How It Influences the Development of Word Reading and Reading Comprehension among At-Risk Readers. AB - The purpose of this study was to examine the extent to which teacher ratings of behavioral attention predicted responsiveness to word reading instruction in first grade and third-grade reading comprehension performance. Participants were 110 first grade students identified as at-risk for reading difficulties who received 20 weeks of intensive reading intervention in combination with classroom reading instruction. Path analysis indicated that teacher ratings of student attention significantly predicted students' word reading growth in first grade even when they were competed against other relevant predictors (phonological awareness, nonword reading, sight word efficiency, vocabulary, listening comprehension, hyperactivity, nonverbal reasoning, and short term memory). Also, student attention demonstrated a significant indirect effect on third grade reading comprehension via word reading, but not via listening comprehension. Results suggest that student attention (indexed by teacher ratings) is an important predictor of at-risk readers' responsiveness to reading instruction in first grade and that first-grade reading growth mediates the relationship between students' attention and their future level of reading comprehension. The importance of considering ways to manage and improve behavioral attention when implementing reading instruction is discussed. PMID- 25110549 TI - Atorvastatin represses the angiotensin 2-induced oxidative stress and inflammatory response in dendritic cells via the PI3K/Akt/Nrf 2 pathway. AB - Dendritic cells (DCs), which are highly proficient antigen-presenting cells, play a complex role in both the initiation and progression of atherosclerosis. We tested the hypothesis that the anti-inflammatory and antioxidant effects of atorvastatin may be partly mediated by the phosphatidylinositol 3-kinase/protein kinase B/transcription factor nuclear factor-erythroid 2-related factor 2 (PI3K/Akt/Nrf 2) pathway via the attenuation of DC maturation, thus reducing the inflammatory and oxidative stress responses. This study showed that angiotensin 2 (Ang 2) induced the maturation of DCs, stimulated CD83, CD40, CD80, and CD86 expression, and increased the secretion of IL-12p70, IL-6, and TNF-alpha. These effects were suppressed by atorvastatin. Atorvastatin also lowered the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), counteracting their initial increases in response to Ang 2 stimulation. Atorvastatin activated Nrf 2 via the PI3K/Akt pathway and thereby promoted Nrf 2 translocation from the cytoplasm to the nucleus in bone marrow-derived dendritic cells (BMDCs), a process that was reversed by the PI3K inhibitor LY294002. Therefore, the regulation of Nrf 2 expression by the PI3K/Akt pathway plays an important role in the regulation of the statin-mediated antioxidant and anti-inflammatory responses in DCs. PMID- 25110550 TI - Oxidative stresses and mitochondrial dysfunction in age-related hearing loss. AB - Age-related hearing loss (ARHL), the progressive loss of hearing associated with aging, is the most common sensory disorder in the elderly population. The pathology of ARHL includes the hair cells of the organ of Corti, stria vascularis, and afferent spiral ganglion neurons as well as the central auditory pathways. Many studies have suggested that the accumulation of mitochondrial DNA damage, the production of reactive oxygen species, and decreased antioxidant function are associated with subsequent cochlear senescence in response to aging stress. Mitochondria play a crucial role in the induction of intrinsic apoptosis in cochlear cells. ARHL can be prevented in laboratory animals by certain interventions, such as caloric restriction and supplementation with antioxidants. In this review, we will focus on previous research concerning the role of the oxidative stress and mitochondrial dysfunction in the pathology of ARHL in both animal models and humans and introduce concepts that have recently emerged regarding the mechanisms of the development of ARHL. PMID- 25110551 TI - Bovine beta-lactoglobulin/fatty acid complexes: binding, structural, and biological properties. AB - Ligand-binding properties of beta-lactoglobulin (beta-lg) are well documented, but the subsequent biological functions are still unclear. Focusing on fatty acids/beta-lg complexes, the structure-function relationships are reviewed in the light of the structural state of the protein (native versus non-native aggregated proteins). After a brief description of beta-lg native structure, the review takes an interest in the binding properties of native beta-lg (localization of binding sites, stoichiometry, and affinity) and the way the interaction affects the biological properties of the protein and the ligand. The binding properties of non-native aggregated forms of beta-lg that are classically generated during industrial processing are also related. Structural changes modify the stoichiometry and the affinity of beta-lg for fatty acids and consequently the biological functions of the complex. Finally, the fatty acid-binding properties of other whey proteins (alpha-lactalbumin, bovine serum albumin) and some biological properties of the complexes are also addressed. These proteins affect beta-lg/fatty acids complex in whey given their competition with beta-lg for fatty acids. PMID- 25110552 TI - Communicating clinical research to reduce cancer risk through diet: Walnuts as a case example. AB - Inflammation is one mechanism through which cancer is initiated and progresses, and is implicated in the etiology of other conditions that affect cancer risk and prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity. Emerging human evidence, primarily epidemiological, suggests that walnuts impact risk of these chronic diseases via inflammation. The published literature documents associations between walnut consumption and reduced risk of cancer, and mortality from cancer, diabetes, and cardiovascular disease, particularly within the context of the Mediterranean Diet. While encouraging, follow-up in human intervention trials is needed to better elucidate any potential cancer prevention effect of walnuts, per se. In humans, the far-reaching positive effects of a plant-based diet that includes walnuts may be the most critical message for the public. Indeed, appropriate translation of nutrition research is essential for facilitating healthful consumer dietary behavior. This paper will explore the translation and application of human evidence regarding connections with cancer and biomarkers of inflammation to the development of dietary guidance for the public and individualized dietary advice. Strategies for encouraging dietary patterns that may reduce cancer risk will be explored. PMID- 25110553 TI - Anti-inflammatory effect of methanol extract from Erigeron Canadensis L. may be involved with upregulation of heme oxygenase-1 expression and suppression of NFkappaB and MAPKs activation in macrophages. AB - BACKGROUND/OBJECTIVES: In this study, we determined the anti-inflammatory activities and the underlying molecular mechanisms of the methanol extract from Erigeron Canadensis L. (ECM) in LPS-stimulated RAW264.7 macrophage cells. MATERIALS/METHODS: The potential anti-inflammatory properties of ECM were investigated by using RAW264.7 macrophages. We used western blot assays and real time quantitative polymerase chain reaction to detect protein and mRNA expression, respectively. Luciferase assays were performed to determine the transactivity of transcription factors. RESULTS: ECM significantly inhibited inducible nitric oxide synthase (iNOS)-derived NO and cyclooxygenase-2 (COX-2) derived PGE2 production in LPS-stimulated RAW264.7 macrophages. These inhibitory effects of ECM were accompanied by decreases in LPS-induced nuclear translocations and transactivities of NFkappaB. Moreover, phosphorylation of mitogen-activated protein kinase (MAPKs) including extracellular signal-related kinase (ERK1/2), p38, and c-jun N-terminal kinase (JNK) was significantly suppressed by ECM in LPS-stimulated RAW264.7 macrophages. Further studies demonstrated that ECM by itself induced heme oxygenase-1 (HO-1) protein expression at the protein levels in dose-dependent manner. However, zinc protoporphyrin (ZnPP), a selective HO-1 inhibitor, abolished the ECM-induced suppression of NO production. CONCLUSIONS: These results suggested that ECM induced HO-1 expression was partly responsible for the resulting anti inflammatory effects. These findings suggest that ECM exerts anti-inflammatory actions and help to elucidate the mechanisms underlying the potential therapeutic values of Erigeron Canadensis L. PMID- 25110554 TI - The effect of long-term supplementation with different dietary omega-6/omega-3 ratios on mineral content and ex vivo prostaglandin E2 release in bone of growing rabbits. AB - BACKGROUND/OBJECTIVES: The aim of this research was to study the different long term effects of consumption of dietary oil sources with varying omega-6/omega-3 (omega-6/omega-3) polyunsaturated fatty acids (PUFAs) ratios on bone marrow fatty acid level, ex vivo prostaglandin E2 (PGE2) release, and mineral content of bone in rabbits. MATERIALS/METHODS: For this purpose, weaning and female New Zealand white rabbits were purchased and randomly divided into five groups and offered ad libitum diets containing 70 g/kg of added oil for 100 days. The dietary lipid treatments were formulated to provide the following ratios of omega-6/omega-3 fatty acids: 8.68 soy bean oil (SBO control), 21.75 sesame oil (SO), 0.39 fish oil (FO), 0.63 algae oil (DHA), and 0.68 algae oils (DHA/ARA). DHA and ARA are two types of marine microalgae of the genus Crypthecodinium cohnii. RESULTS: The dietary treatments had significant effects on the bone marrow fatty acids of rabbits. Rabbits fed the FO diet, containing the highest omega-3 PUFA concentration, and those fed the SBO diet showed the highest omega-6 PUFA. On the other hand, a positive correlation was observed between Ex vivo PGE2 level and the omega-6/omega-3 dietary ratio. Significant effects of dietary treatment on femur Ca, P, Mg, and Zn contents were observed in both genders. CONCLUSIONS: Findings of the current study clearly demonstrated that dietary PUFA, particularly omega-6/omega-3 and ARA/EPA ratios are important factors in determining bone marrow fatty acid profile, and this in turn determines the capacity of bone for synthesis of PGE2, thereby reducing bone resorption and improving bone mass during growth. PMID- 25110555 TI - Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose. AB - BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and 50 ug/mL of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and 50 ug/mL of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs. PMID- 25110556 TI - Anti-proliferative and angio-suppressive effect of Stoechospermum marginatum (C. Agardh) Kutzing extract using various experimental models. AB - BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis. PMID- 25110557 TI - Protective effects of Acanthopanax divaricatus extract in mouse models of Alzheimer's disease. AB - BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity. MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models of Alzheimer's disease (AD); intracerebroventricular injection of beta-amyloid peptide (Abeta) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every 12 hrs started from one day prior to injection of Abeta1-42 until evaluation) effectively blocked Abeta1-42-induced impairment in passive avoidance performance, and Abeta1-42-induced increase in immunoreactivities of glial fibrillary acidic protein and interleukin (IL)-1alpha in the hippocampus. In addition, it alleviated the Abeta1-42-induced decrease in acetylcholine and increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice, chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six months from the age of six to 12 months) resulted in significantly enhanced performance of the novel-object recognition task, and reduced amyloid deposition and IL-1beta in the brain. CONCLUSIONS: The results of this study suggest that ADA stem extract may be useful for prevention and treatment of AD. PMID- 25110558 TI - Apple pectin, a dietary fiber, ameliorates myocardial injury by inhibiting apoptosis in a rat model of ischemia/reperfusion. AB - BACKGROUND/OBJECTIVE: Myocardial cell death due to occlusion of the coronary arteries leads to myocardial infarction, a subset of coronary heart disease (CHD). Dietary fiber is known to be associated with a reduced risk of CHD, the underlying mechanisms of which were suggested to delay the onset of occlusion by ameliorating risk factors. In this study, we tested a hypothesis that a beneficial role of dietary fiber could arise from protection of myocardial cells against ischemic injury, manifested after occlusion of the arteries. MATERIALS/METHODS: Three days after rats were fed apple pectin (AP) (with 10, 40, 100, and 400 mg/kg/day), myocardial ischemic injury was induced by 30 min ligation of the left anterior descending coronary artery, followed by 3 hr reperfusion. The area at risk and infarct area were evaluated using Evans blue dye and 2,3,5-triphenyltetrazolium chloride (TTC) staining, respectively. DNA nicks reflecting the extent of myocardial apoptosis were assessed by TUNEL assay. Levels of cleaved caspase-3, Bcl-2, and Bax were assessed by immunohistochemistry. RESULTS: Supplementation of AP (with 100 and 400 mg/kg/day) resulted in significantly attenuated infarct size (IS) (ratio of infarct area to area at risk) by 21.9 and 22.4%, respectively, in the AP-treated group, compared with that in the control group. This attenuation in IS showed correlation with improvement in biomarkers involved in the apoptotic cascades: reduction of apoptotic cells, inhibition of conversion of procaspase-3 to caspase-3, and increase of Bcl-2/Bax ratio, a determinant of cell fate. CONCLUSIONS: The findings indicate that supplementation of AP results in amelioration of myocardial infarction by inhibition of apoptosis. Thus, the current study suggests that intake of dietary fiber reduces the risk of CHD, not only by blocking steps leading to occlusion, but also by protecting against ischemic injury caused by occlusion of the arteries. PMID- 25110559 TI - Protective effect of the standardized green tea seed extract on UVB-induced skin photoaging in hairless mice. AB - BACKGROUND/OBJECTIVES: Ultraviolet B (UVB) irradiation on skin can induce production of reactive oxygen species (ROS), which cause expression of matrix metalloproteinases (MMPs) and collagen degradation. Thus, chronic exposure of skin to UVB irradiation leads to histological changes consistent with aging, such as wrinkling, abnormal pigmentation, and loss of elasticity. We investigated the protective effect of the standardized green tea seed extract (GSE) on UVB-induced skin photoaging in hairless mice. MATERIALS/METHODS: Skin photoaging was induced by UVB irradiation on the back of Skh-1 hairless mice three times per week and UVB irradiation was performed for 10 weeks. Mice were divided into six groups; normal control, UVB irradiated control group, positive control (UVB + dietary supplement of vitamin C 100 mg/kg), GSE 10 mg/kg (UVB + dietary supplement of GSE 10 mg/kg), GSE 100 mg/kg (UVB + dietary supplement of GSE 100 mg/kg), and GSE 200 mg/kg (UVB + dietary supplement of GSE 200 mg/kg). RESULTS: The dietary supplement GSE attenuated UVB irradiation-induced wrinkle formation and the decrease in density of dermal collagen fiber. In addition, results of the antioxidant analysis showed that GSE induced a significant increase in antioxidant enzyme activity compared with the UVB irradiation control group. Dietary supplementation with GSE 200 mg/kg resulted in a significant decrease in expression of MMP-1, MMP-3, and MMP-9 and an increase in expression of TIMP and type-1 collagen. CONCLUSIONS: Findings of this study suggest that dietary supplement GSE could be useful in attenuation of UVB irradiation-induced skin photoaging and wrinkle formation due to regulation of antioxidant defense systems and MMPs expression. PMID- 25110560 TI - Effect of Hominis Placenta on cutaneous wound healing in normal and diabetic mice. AB - BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice. MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson's trichrome staining for collagen study. RESULTS: Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling. PMID- 25110561 TI - Improvement in metabolic parameters in obese subjects after 16 weeks on a Brazilian-staple calorie-restricted diet. AB - BACKGROUND/OBJECTIVES: The standard pattern of Brazilian food consumption is based on the combination of rice and beans served together in the main meals. This study assessed the effects of Brazilian-staple calorie-restricted (BS-diet) dietary advice, with brown rice and beans, on metabolic parameters, body composition, and food intake in overweight/obese subjects. SUBJECTS/METHODS: Twentyseven subjects were randomly assigned to a conventional-type calorie restricted diet (CT-diet) (n = 13) or a BS-diet (n = 14). Glucose metabolism, lipid profile, anthropometric and body composition parameters, and food intake were measured before and after 16 weeks. Paired t-tests/Wilcoxon tests were used for comparison of differences from baseline and unpaired t-tests/Mann-Whitney tests were used for comparison of differences between the groups. RESULTS: After 16 weeks, both groups showed reductions in weight and waist circumference (P < 0.02), and the BS-diet group showed a decrease in body fat (P = 0.0001), and significant improvement in glucose metabolism (fasting plasma glucose, glucose and insulin areas under the curve, Cederholm index, and HOMA2-%beta) (P <= 0.04) and lipid profile (cholesterol, triacylglycerol, LDL-c, VLDL-c, and cholesterol/HDL-c ratio) (P <= 0.05). In addition, the BS-diet group showed significant improvement in HOMA2-%beta, compared to the CT-diet group (P = 0.03). The BS-diet group also showed a significant reduction in energy, lipids, carbohydrate, and cholesterol intake (P <= 0.04) and an increase in fiber intake (P <= 0.001), while the CT-diet group showed a significant reduction in intake of energy, macronutrients, PUFA, and cholesterol (P <= 0.002). CONCLUSIONS: These results demonstrate the benefits of the BS-diet on metabolic parameters in obese subjects. PMID- 25110562 TI - Plasma adipocytokines and antioxidants-status in Korean overweight and obese females with dyslipidemia. AB - BACKGROUD/OBEJECTIVES: It is hypothesized that obese people with dyslipidemia is more likely to have increased oxidative stress and decreased antioxidant status, in comparison with the controls who were obese without dyslipidemia. Thus, the aims of the present study were to determine the dietary intakes, plasma adipokines, and antioxidative systems between obese with dyslipidemia and obese without dyslipidemia were investigated. SUBJECTS/METHODS: Female subjects who were between 20 and 55 years old, and whose BMI was 23 or greater were recruited. Subjects who met the criteria of BMI >= 23, total cholesterol >= 200 mg/dL, LDL cholesterol >= 130 mg/dL, and TG >= 110 mg/dL were categorized Obese with dyslipidemia. Anthropometric measurements and blood biochemical tests were conducted. The diet survey was conducted by a trained dietitian using two days of 24 hour dietary recall. The lipid peroxidation, the plasma total antioxidant capacity (TAC), the activities of antioxidantive enzymes, and various antioxidantive vitamins levels were determined. RESULTS: Plasma adiponectin and leptin levels were also determined. There were no significant differences for age, Body Mass index (BMI), and body fat (%), waist-size between two groups. Obese with dyslipidemia had significantly high levels of total cholesterol, triglyceride, LDL-cholesterol, the ratio of total cholesterol/HDL-C, and the ratio of HDL-C/LDL-C, respectively. Blood alkaline phosphatase level was statistically different between the two groups (P < 0.05). No statistical significance in dietary intake between two groups was shown. In case of obese with dyslipidemia group, the levels of GSH-Px (P < 0.05) and catalase (P < 0.05) as well as adjusted blood retinol (P < 0.05) and tocopherol level (P < 0.05) were significantly low. However, the plasma concentration of leptin was significantly high (P < 0.05). CONCLUSIONS: Obesity with dyslipidemia was shown to have high arthtrogenic index, depleted antioxidant status, and higher blood leptin levels which suggest higher risks of oxidative stress and cardiovascular diseases. PMID- 25110563 TI - Factors contributing to participation in food assistance programs in the elderly population. AB - BACKGROUND/OBJECTIVES: The study objectives were to examine the participation rate in food assistance programs and explore the factors that contribute to such participation among the Korean elderly population. SUBJECTS/METHODS: The study sample comprised 3,932 respondents aged 65 years or older who were selected from a secondary data set, the fourth Korean Welfare Panel Study (KoWePS). The factors, related to participation in programs were examined based on the predisposing, enabling and need factors of the help-seeking behavior model. Multiple logistic regression analysis was used to select the best contributors among the factors related to program participation. RESULTS: The predisposing rate in food assistance programs was 8.5% (7.1% for men and 10.4% for women). When all variables were included in the model, living without spouse, no formal education, low income, having social security benefits and food insecurity in elderly men, and age, low income, having social security benefits and feeling poor in elderly women were significantly related to a higher tendency to program participation. CONCLUSIONS: The predisposing and need factors, such as living without spouse, low education level, food insecurity and feeling poor were important for program participation, as well as enabling factors, such as household income and social security benefits. A comprehensive approach considering these factors to identify the target population for food assistance programs is needed to increase the effectiveness and target population penetration of these programs. PMID- 25110564 TI - Structural relations of late night snacking choice attributes and health promotion behaviors according to dietary style of industrial workers. AB - BACKGROUND/OBJECTIVES: This research was conducted to develop a construct model regarding the dietary style, late night snacking choice attributes and health promotion behaviors of industrial workers. SUBJECTS/METHODS: The surveys were collected during the period between January and February 2013. A statistical analysis of 888 industrial workers was conducted using SPSS 12.0 for Windows and SEM (Structural Equation Model) using AMOS (Analysis of Moment Structure) 5.0 statistics package. RESULTS: The results of the correlations between all variables showed significant positive correlations (P < 0.05). Results of factors analysis on dietary styles were categorized into five factors and health promotion behaviors were categorized into four. The reliability of these findings was supported by a Cronbach's alpha coefficient of 0.6 and higher for all other factors. After obtaining the factors from processing an exploratory factor analysis and the end results supported the validity. In an attempt to study the late night snacking choice attributes in accordance to dietary styles and the health promotion behaviors of industrial workers, a structural equation model was constructed and analyzed. CONCLUSIONS: All tests proved the model satisfied the recommended levels of the goodness on fit index, and thus, the overall research model was proved to be appropriate. PMID- 25110565 TI - Analysis of micromineral contents of school meals. AB - BACKGROUND/OBJECTIVES: Korean ordinary diets are referred to be good for human health in worldwide. However it is uncertain whether they provide microminerals enough for growth and health of teenagers. A main purpose of this study was to identify micromineral contents in school meals. MATERIALS/METHODS: The fifty cuisines were collected from elementary schools and middle schools in Gyeongnam area. The contents of Fe, Zn, Cu and Mn among microminerals were analyzed by using ICP-OES method. Data were expressed as mean, standard deviation and range value and linear regression analysis performed. RESULTS: Fe level of Pangibuseotpaprika-salad was the highest among side-dishes (average 346.6 ug) and Zn level of Sullung-tang was highest among soups (average 229.1 ug). Cu level of Buchu-kimchi was the highest among kimchies (average 217.5 ug) and Mn level of Gumeunkongyangnyum-gui was highest among side-dishes (average 198.4 ug). Generally cooked-rices as main dish had relative smaller amounts of microminerals than the other cuisines. The results showed that the ratio of Cu : Fe : Zn was approximately 12 : 4 : 1 and the relationship between Fe versus Zn or Fe versus Cu was significantly positive. CONCLUSION: Comparing to Korean Dietary Recommended Intakes (KDRI) level, school meals provided not sufficient amount (<25% DRI) of Fe, Zn or Mn, while they did excessive amount (>125% DRI) of Cu. PMID- 25110566 TI - Association between high sensitivity C-reactive protein and dietary intake in Vietnamese young women. AB - BACKGROUND/OBJECTIVES: High sensitivity C-reactive protein (hsCRP) is a strong independent predictor of future cardiovascular disease (CVD) risk. We evaluated the relationship between hsCRP and dietary intake in apparently healthy young women living in southern Vietnam. SUBJECTS/METHODS: Serum hsCRP was measured and dietary intake data were obtained using the 1-day 24-hour recall method in women (n = 956; mean age, 25.0 +/- 5.7 years) who participated in the International Collaboration Study for the Construction of Asian Cohort of the Korean Genome and Epidemiology Study (KoGES) in 2011. RESULTS: Women in the high risk group (> 3 mg/L) consumed fewer fruits and vegetables, total plant food, potassium, and folate than those in the low risk group (< 1 mg/L). A multiple regression analysis after adjusting for covariates revealed a significant negative association between hsCRP and fruit and vegetable consumption. A logistic regression analysis showed that the odds ratio (OR) of having a high hsCRP level in women with the highest quartiles of consumption of fruits and vegetables [OR, 0.391; 95% confidence interval (CI), 0.190-0.807], potassium [OR, 0.425; 95% CI, 0.192-0.939] and folate [OR, 0.490; 95% CI, 0.249-0.964] were significantly lower than those in the lowest quartiles. CONCLUSIONS: These results suggest that, in young Vietnamese women, an increased consumption of fruit and vegetables might be beneficial for serum hsCRP, a risk factor for future CVD events. PMID- 25110567 TI - The relationship of dietary sodium, potassium, fruits, and vegetables intake with blood pressure among Korean adults aged 40 and older. AB - BACKGROUND/OBJECTIVES: The inverse relationships of combined fruits and vegetables intake with blood pressure have been reported. However, whether there are such relationships with salty vegetables has rarely been investigated in epidemiologic studies. We evaluated the relation of combined and separate intake of fruits, vegetable intakes, and salty vegetables, as well as sodium and potassium, with blood pressure among the middle-aged and elderly populations. SUBJECTS/METHODS: The present cross-sectional analysis of a prospective cohort baseline survey was performed with 6,283 subjects (2,443 men and 3,840 women) and free of hypertension, diabetes, cardiovascular diseases, and cancer. Dietary data were collected by trained interviewers using food frequency questionnaire. RESULTS: The significantly inverse linear trend of diastolic blood pressure (DBP) was found in fruits and non-pickled vegetables (81.2 mmHg in the lowest quintile vs 79.0 mmHg in the highest quintile, P for trend = 0.0040) and fruits only (80.9 mmHg in the lowest quintile vs 79.4 mmHg in the highest quintile, P for trend = 0.0430) among men. In contrast, sodium and sodium to potassium ratio were positively related with blood pressure among men (DBP, 78.8 mmHg in the lowest quintile vs 80.6 mmHg in the highest quintile, P for trend = 0.0079 for sodium; DBP, 79.0 mmHg in the lowest quintile vs 80.7 mmHg in the highest quintile, P for trend = 0.0199 and SBP, 123.8 mmHg in the lowest quintile vs 125.9 mmHg in the highest quintile for sodium/potassium). Kimchies consumption was positively related to DBP for men (78.2 mmHg in the lowest quintile vs 80.9 mmHg in the highest quintile for DBP, P for trend = 0.0003). Among women, these relations were not found. CONCLUSION: Fruits and/or non-pickled vegetables may be inversely, but sodium, sodium to potassium, and Kimchies may be positively related to blood pressure among men. PMID- 25110568 TI - Association between family structure and food group intake in children. AB - BACKGROUNDS/OBJECTOVES: Family has an impact on dietary intake of children as a proximal food environment and family structures are changing and becoming more diverse. This study was performed to identify the association between family structure and food group intake of children aged 3-18 years in Korea. SUBJECTS/METHODS: A total of 3,217 children with complete data on variables for household information, dietary intake and sampling weights were obtained from 2010-2011 Korea National Health and Nutrition Examination Survey. Children's family structure was classified into 3 groups (Living with both parents, Living with one parent and Living without parents). To evaluate children's food group intake, scores of individual food groups ('Grains', 'Meat, Fish, Eggs and Beans', 'Vegetables', 'Fruits' and 'Milk and Dairy products') was calculated from percent adherence to the recommended servings of the Korean Food Guidance System (KFGS). 'Food group mean score' was obtained by calculating the average of five food group scores. RESULTS: After adjusting for age, sex, number of family members, and household income, children living with both parents had higher scores in 'Fruits' (P < 0.01), 'Milk and Dairy products' (P < 0.05), and mean score of individual food group score (P < 0.001) compared to children living with one parent. Individual food group scores and mean scores of individual food group scores were associated with different socio-demographic factors in study children. Family structure was associated with 'Fruits,' 'Milk and Dairy products' score and mean scores of food group scores. CONCLUSIONS: These results suggested that different approach might be required to solve nutrition problem in children depending on their family structure and other socio-demographic factors. PMID- 25110569 TI - Moderate diet-induced weight loss is associated with improved insulin sensitivity in middle-aged healthy obese Korean women. AB - BACKGROUND/OBJECTIVE: The goal of the present study was to investigate the effects of moderate caloric restriction on beta-cell function and insulin sensitivity in middle-aged obese Korean women. SUBJECTS/METHODS: Fifty-seven obese pre-menopausal Korean women participated in a 12-week calorie restriction program. Data on total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and fasting serum levels of glucose, insulin, C-peptide, blood pressure, leptin and anthropometrics were collected. A dietary intake assessment was based on three days of food recording. Additionally, beta-cell function [homeostasis model assessment of beta-cell (HOMA-beta), insulinogenic index (ISI), C-peptide:glucose ratio, and area under curve insulin/glucose (AUCins/glu)] and insulin sensitivity [homeostasis model assessment for insulin resistance (HOMA-IR), Quantitative insulin-sensitivity check index (QUICKI) and Matsuda index (MI)] were recorded. RESULTS: When calories were reduced by an average of 422 kcal/day for 12 weeks, BMI (-2.7%), body fat mass (-10.2%), and waist circumference (-5%) all decreased significantly (P < 0.05). After calorie restriction, weight, body fat percentage, hip circumference, BP, TC, HDL-C, LDL-C, plasma glucose at fasting, insulin at fasting and 120 min, AUCglu and the insulin area under the curve all decreased significantly (all P < 0.05), while insulin sensitivity (HOMA-IR, QUICKI and Matsuda index) measured by OGTT improved significantly (P < 0.01). CONCLUSIONS: Moderate weight loss due to caloric restriction with reduction in insulin resistance improves glucose tolerance and insulin sensitivity in middle-aged obese women and thereby may help prevent the development of type 2 diabetes mellitus. PMID- 25110570 TI - Relationships of adolescent's dietary habits with personality traits and food neophobia according to family meal frequency. AB - BACKGROUND: A higher frequency of family meals is associated with good dietary habits in young people. This study focused on the relationships of family meal frequency with food neophobia and personality traits in adolescents. SUBJECTS/METHOD: For this purpose, we administered a survey to 495 middle school students in Seoul metropolitan city, after which the data were analyzed using the SPSS (18.0) program. Pearson correlation was used to determine the relationships among dietary habits, personality traits, and food neophobia according to frequency of family meals. RESULTS: Dietary habits, personality traits, and food neophobia all showed significant differences according to the frequency of family meals. Further, eating regular family meals was associated with good dietary habits (P < 0.001) and was linked with improved extraversion, agreeableness, conscientiousness, emotional stability, and openness/intellect (P < 0.001). On the other hand, it showed a negative relationship with food neophobia (P < 0.001). The relationship between dietary habits and food neophobia showed a negative correlation (P < 0.01). The relationship between dietary habits and personality traits showed a positive correlation (P < 0.01). Lastly, the relationship between personality traits and food neophobia showed a negative correlation (P < 0.01). CONCLUSION: Based on the results of the study, the frequency of family meals affects dietary habits, personality traits, and food neophobia in adolescents. PMID- 25110571 TI - Antifungal Amphiphilic Aminoglycosides. AB - The attachment of alkyl and other hydrophobic groups to traditional antibacterial kanamycins and neomycins creates amphiphilic aminoglycosides with altered antimicrobial properties. In this review, we summarize the discovery of amphiphilic kanamycins that are antifungal, but not antibacterial, and that inhibit the growth of fungi by perturbation of plasma membrane functions. With low toxicities against plant and mammalian cells, they appear to specifically target the fungal plasma membrane. These new antifungal agents offer new options for fighting fungal pathogens and are examples of reviving old drugs to confront new therapeutic challenges. PMID- 25110572 TI - Nebulin interactions with actin and tropomyosin are altered by disease-causing mutations. AB - BACKGROUND: Nemaline myopathy (NM) is a rare genetic muscle disorder, but one of the most common among the congenital myopathies. NM is caused by mutations in at least nine genes: Nebulin (NEB), alpha-actin (ACTA1), alpha-tropomyosin (TPM3), beta-tropomyosin (TPM2), troponin T (TNNT1), cofilin-2 (CFL2), Kelch repeat and BTB (POZ) domain-containing 13 (KBTBD13), and Kelch-like family members 40 and 41 (KLHL40 and KLHL41). Nebulin is a giant (600 to 900 kDa) filamentous protein constituting part of the skeletal muscle thin filament. Around 90% of the primary structure of nebulin is composed of approximately 35-residue alpha-helical domains, which form super repeats that bind actin with high affinity. Each super repeat has been proposed to harbor one tropomyosin-binding site. METHODS: We produced four wild-type (WT) nebulin super repeats (S9, S14, S18, and S22), 283 to 347 amino acids long, and five corresponding repeats with a patient mutation included: three missense mutations (p.Glu2431Lys, p.Ser6366Ile, and p.Thr7382Pro) and two in-frame deletions (p.Arg2478_Asp2512del and p.Val3924_Asn3929del). We performed F-actin and tropomyosin-binding experiments for the nebulin super repeats, using co-sedimentation and GST (glutathione-S-transferase) pull-down assays. We also used the GST pull-down assay to test the affinity of WT nebulin super repeats for WT alpha- and beta-tropomyosin, and for beta-tropomyosin with six patient mutations: p.Lys7del, p.Glu41Lys, p.Lys49del, p.Glu117Lys, p.Glu139del and p.Gln147Pro. RESULTS: WT nebulin was shown to interact with actin and tropomyosin. Both the nebulin super repeats containing the p.Glu2431Lys mutation and nebulin super repeats lacking exon 55 (p.Arg2478_Asp2512del) showed weak affinity for F-actin compared with WT fragments. Super repeats containing the p.Ser6366Ile mutation showed strong affinity for actin. When tested for tropomyosin affinity, super repeats containing the p.Glu2431Lys mutation showed stronger binding than WT proteins to tropomyosin, and the super repeat containing the p.Thr7382Pro mutation showed weaker binding than WT proteins to tropomyosin. Super repeats containing the deletion p.Val3924_Asn3929del showed similar affinity for actin and tropomyosin as that seen with WT super repeats. Of the tropomyosin mutations, only p.Glu41Lys showed weaker affinity for nebulin (super repeat 18). CONCLUSIONS: We demonstrate for the first time the existence of direct tropomyosin-nebulin interactions in vitro, and show that nebulin interactions with actin and tropomyosin are altered by disease-causing mutations in nebulin and tropomyosin. PMID- 25110573 TI - Seizure evoked regulation of LIM-HD genes and co-factors in the postnatal and adult hippocampus. AB - The LIM-homeodomain (LIM-HD) family of transcription factors is well known for its functions during several developmental processes including cell fate specification, cell migration and axon guidance, and its members play fundamental roles in hippocampal development. The hippocampus is a structure that displays striking activity dependent plasticity. We examined whether LIM-HD genes and their co-factors are regulated during kainic acid induced seizure in the adult rat hippocampus as well as in early postnatal rats, when the hippocampal circuitry is not fully developed. We report a distinct and field-specific regulation of LIM-HD genes Lhx1, Lhx2, and Lhx9, LIM-only gene Lmo4, and cofactor Clim1a in the adult hippocampus after seizure induction. In contrast none of these genes displayed altered levels upon induction of seizure in postnatal animals. Our results provide evidence of temporal and spatial seizure mediated regulation of LIM-HD family members and suggest that LIM-HD gene function may be involved in activity dependent plasticity in the adult hippocampus. PMID- 25110574 TI - Prism adaptation does not alter configural processing of faces. AB - Patients with hemispatial neglect ('neglect') following a brain lesion show difficulty responding or orienting to objects and events on the left side of space. Substantial evidence supports the use of a sensorimotor training technique called prism adaptation as a treatment for neglect. Reaching for visual targets viewed through prismatic lenses that induce a rightward shift in the visual image results in a leftward recalibration of reaching movements that is accompanied by a reduction of symptoms in patients with neglect. The understanding of prism adaptation has also been advanced through studies of healthy participants, in whom adaptation to leftward prismatic shifts results in temporary neglect-like performance. Interestingly, prism adaptation can also alter aspects of non lateralised spatial attention. We previously demonstrated that prism adaptation alters the extent to which neglect patients and healthy participants process local features versus global configurations of visual stimuli. Since deficits in non-lateralised spatial attention are thought to contribute to the severity of neglect symptoms, it is possible that the effect of prism adaptation on these deficits contributes to its efficacy. This study examines the pervasiveness of the effects of prism adaptation on perception by examining the effect of prism adaptation on configural face processing using a composite face task. The composite face task is a persuasive demonstration of the automatic global-level processing of faces: the top and bottom halves of two familiar faces form a seemingly new, unknown face when viewed together. Participants identified the top or bottom halves of composite faces before and after prism adaptation. Sensorimotor adaptation was confirmed by significant pointing aftereffect, however there was no significant change in the extent to which the irrelevant face half interfered with processing. The results support the proposal that the therapeutic effects of prism adaptation are limited to dorsal stream processing. PMID- 25110575 TI - Nasal decongestant and chronic headache: a case of naphazoline overuse headache? AB - BACKGROUND: Chronic headache is an incapacitating condition afflicting patients at least for 15 days per month. In the most cases it is developed as a consequence of an excessive use of symptomatic drugs. CASE: Here we report the case of a 34 year-old man suffering from chronic headache possibly related to the overuse of naphazoline nitrate nasal decongestant, used to treat a supposed chronic sinusitis. However, the patient did not suffer from sinusitis, but from a medication overuse headache (ICHD-II 8.3; ICD-10 44.41) that appeared to be due to excessive use of naphazoline. CONCLUSION: The use of naphazoline nitrate may result in an analgesic effect upon first use, through activation of adrenergic and opioidergic systems, followed by a pro-migraine effect via a late induction of an inflammatory cascade, modulated by nitric oxide and arachidonic acid. The observation that naphazoline detoxification relieved the patient's headache, indicates that prolonged use of naphazoline may cause chronic headaches. Therefore, physicians should ask for details on the use of nasal decongestants in patients complaining of chronic headache, as they could potentially be suffering from a medication-overuse headache. PMID- 25110576 TI - Functional characterization of Candida albicans Hos2 histone deacetylase. AB - Candida albicans is a mucosal commensal organism in normal individuals, but is a major pathogen causing systemic and mucosal infections in immunocompromised individuals. Azoles have been very effective anti-fungal agents and the mainstay in treating opportunistic mold and yeast infections. Azole resistant strains have emerged compromising the utility of this class of drugs. It has been shown that azole resistance can be reversed by the co-administration of a histone deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report here the cloning and functional characterization of HOS2 (High Osmolarity Sensitive) , a gene coding for fungal histone deacetylase from C. albicans. Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not inhibited by class I inhibitors such MS-275. Purified Hos2 protein consistently deacetylated tubulins, rather than histones from TSA-treated cells. This in vitro enzymatic assay, which is amenable to high throughput could be used for screening potent fungal Hos2 inhibitors that could be a potential anti-fungal adjuvant. Hos2 has been reported to be a putative NAD+ dependent histone deacetylase, a feature of sirtuins. We assayed for sirtuin activation with resveratrol and purified Hos2 protein and did not find any sirtuin activity. PMID- 25110577 TI - Accumulation of oocytes and/or embryos by vitrification: a new strategy for managing poor responder patients undergoing pre implantation diagnosis. AB - BACKGROUND: Low (or poor) responder patients are women who require large doses of stimulation medications and produce less than an optimal number of oocytes during IVF cycles. Low responder patients produce few oocytes and embryos, which significantly reduces their chances for success in a preimplantation genetic diagnosis (PGD) cycle. Accumulation of vitrified oocytes or embryos before the actual PGD cycle is a possible strategy that might increase patient's chances for a healthy pregnancy. AIM OF THE STUDY: This retrospective study evaluates the efficacy of a PGD program in low responder patients after repeated ovarian stimulation cycles with cumulative vitrification of oocytes and embryos. METHODS: Over a period of 30 months, 13 patients entering the PGD program were identified as poor responders after their first ovarian stimulation. These patients started a PGD cycle for one of the following indications: history of recurrent implantation failure (n=1), cystic fibrosis (n=1), X-linked microtubular myopathy (n=1), recurrent miscarriages (n=5), Duchene muscular dystrophy (n=1), chromosomal translocation (n=1) and high sperm aneuploidy (n=1). After multiple ovarian hormonal stimulations patients had either all mature oocytes (Group A; 3 patients) or all of their day 2 embryos vitrified (group B; 10 patients). Mean total number of oocyte collections per patient was 2.3 (range: 2 - 5 cycles). RESULTS: In the actual PGD cycle, all vitrified oocytes from group A patients were warmed and underwent intra cytoplasmic sperm injection (ICSI) followed by culture up to day 3. For group B patients all vitrified day 2 embryos were warmed and cultured overnight. On day 3 of culture, all embryos from Group A and B had blastomere biopsy followed by genetic analysis. In group A, 20 embryos were found suitable for biopsy and genetic analysis; at least one healthy embryo was available for transfer for each patient. For group B, 72 embryos in total were available for biopsy and PGD. All patients, except one, had at least one healthy day 5 embryo for transfer (mean number of 2.1 embryos per transfer). Nine patients had a clinical pregnancy; 7 patients delivered a healthy baby. CONCLUSION: Low responder patients entering a PGD program might increase their chances for a healthy pregnancy by repeat ovarian stimulation in combination with cumulative oocyte or embryo vitrification. PMID- 25110578 TI - C-Sibelia: an easy-to-use and highly accurate tool for bacterial genome comparison. AB - We present C-Sibelia, a highly accurate and easy-to-use software tool for comparing two closely related bacterial genomes, which can be presented as either finished sequences or fragmented assemblies. C-Sibelia takes as input two FASTA files and produces: (1) a VCF file containing all identified single nucleotide variations and indels; (2) an XMFA file containing alignment information. The software also produces Circos diagrams visualizing high level genomic architecture for rearrangement analyses. C-Sibelia is a part of the Sibelia comparative genomics suite, which is freely available under the GNU GPL v.2 license at http://sourceforge.net/projects/sibelia-bio. C-Sibelia is compatible with Unix-like operating systems. A web-based version of the software is available at http://etool.me/software/csibelia. PMID- 25110579 TI - Ten things to get right for marine conservation planning in the Coral Triangle. AB - Systematic conservation planning increasingly underpins the conservation and management of marine and coastal ecosystems worldwide. Amongst other benefits, conservation planning provides transparency in decision-making, efficiency in the use of limited resources, the ability to minimise conflict between diverse objectives, and to guide strategic expansion of local actions to maximise their cumulative impact. The Coral Triangle has long been recognised as a global marine conservation priority, and has been the subject of huge investment in conservation during the last five years through the Coral Triangle Initiative on Coral Reefs, Fisheries and Food Security. Yet conservation planning has had relatively little influence in this region. To explore why this is the case, we identify and discuss 10 challenges that must be resolved if conservation planning is to effectively inform management actions in the Coral Triangle. These are: making conservation planning accessible; integrating with other planning processes; building local capacity for conservation planning; institutionalising conservation planning within governments; integrating plans across governance levels; planning across governance boundaries; planning for multiple tools and objectives; understanding limitations of data; developing better measures of progress and effectiveness; and making a long term commitment. Most important is a conceptual shift from conservation planning undertaken as a project, to planning undertaken as a process, with dedicated financial and human resources committed to long-term engagement. PMID- 25110580 TI - Positioning a proned patient with cauda equina syndrome who presents at 15 weeks gestation: a case report. AB - Cauda equina syndrome is a neurosurgical emergency that requires prompt intervention to prevent irreversible spinal cord paralysis. This article describes how we managed a case of an obese pregnant patient who was placed in the prone position for surgery. We discuss the evidence behind the management options and choice of operating tables available. PMID- 25110581 TI - Factors that contribute to social media influence within an Internal Medicine Twitter learning community. AB - Medical societies, faculty, and trainees use Twitter to learn from and educate other social media users. These social media communities bring together individuals with various levels of experience. It is not known if experienced individuals are also the most influential members. We hypothesize that participants with the greatest experience would be the most influential members of a Twitter community. We analyzed the 2013 Association of Program Directors in Internal Medicine Twitter community. We measured the number of tweets authored by each participant and the number of amplified tweets (re-tweets). We developed a multivariate linear regression model to identify any relationship to social media influence, measured by the PageRank. Faculty (from academic institutions) comprised 19% of the 132 participants in the learning community (p < 0.0001). Faculty authored 49% of all 867 tweets (p < 0.0001). Their tweets were the most likely to be amplified (52%, p < 0.01). Faculty had the greatest influence amongst all participants (mean 1.99, p < 0.0001). Being a faculty member had no predictive effect on influence (beta = 0.068, p = 0.6). The only factors that predicted influence (higher PageRank) were the number of tweets authored (p < 0.0001) and number of tweets amplified (p < 0.0001) The status of "faculty member" did not confer a greater influence. Any participant who was able to author the greatest number of tweets or have more of his/her tweets amplified could wield a greater influence on the participants, regardless of his/her authority. PMID- 25110582 TI - Tooth eruption sequence and dental crowding: a case-control study. AB - When cases of dental crowding are identified and diagnosed promptly, interceptive orthodontics is particularly successful. AIM: To assess the differences in the eruption sequence of the mandibular canine and first premolar teeth in children with and without dental crowding. MATERIALS AND METHODS: Children who attended the Shiraz Dental School's orthodontic clinic (Iran) from September to December 2012 were enrolled in this case-control study. Tooth size arch length discrepancy (TSALD) of all 8-10 year olds was calculated from patients' dental models. Thirty six children were randomly selected from those with TSALD of equal or less than 4mm (those with crowding). Each selected case was matched for sex and age with another child (as control) with TSALD>-4mm attending the same clinic, in the same time period. The existing panoramic radiographs were traced and the eruption percentages were measured for mandibular canine and first premolar teeth. The mean difference between canine and first premolar eruption percentages was compared between the case and control groups using the SPSS (version PASW 18) software and a paired sample t-test. RESULTS: Canine and first premolar eruption percentages in the case group were 65.82+/-13.00 and 78.92+/-10.15 percent, respectively. The mean eruption percentages for canines and first premolars of the control group were 74.12+/-14.55 and 75.47+/-11.60 percent, respectively. There was a significant difference in pre-eruptive positions of canine and first premolar teeth in those with moderate to severe crowding when compared to the control group (p<0.001). CONCLUSION: These findings may improve the early diagnosis of children with high risk of developing moderate to severe crowding during mixed dentition. PMID- 25110583 TI - Vitellogenin family gene expression does not increase Drosophila lifespan or fecundity. AB - One of the most striking patterns in comparative biology is the negative correlation between lifespan and fecundity observed in comparisons among species. This pattern is consistent with the idea that organisms need to allocate a fixed energy budget among competing demands of growth, development, reproduction and somatic maintenance. However, exceptions to this pattern have been observed in many social insects, including ants, bees, and termites. In honey bees ( Apis mellifera), Vitellogenin ( Vg), a yolk protein precursor, has been implicated in mediating the long lifespan and high fecundity of queen bees. To determine if Vg like proteins can regulate lifespan in insects generally, we examined the effects of expression of Apis Vg and Drosophila CG31150 (a Vg-like gene recently identified as cv-d) on Drosophila melanogaster lifespan and fecundity using the RU486-inducible GeneSwitch system. For all genotypes tested, overexpression of Vg and CG31150 decreased Drosophila lifespan and did not affect total or age specific fecundity. We also detected an apparent effect of the GeneSwitch system itself, wherein RU486 exposure (or the GAL4 expression it induces) led to a significant increase in longevity and decrease in fecundity in our fly strains. This result is consistent with the pattern reported in a recent meta-analysis of Drosophila aging studies, where transgenic constructs of the UAS/GAL4 expression system that should have no effect (e.g. an uninduced GeneSwitch) significantly extended lifespan in some genetic backgrounds. Our results suggest that Vg-family genes are not major regulators of Drosophila life history traits, and highlight the importance of using appropriate controls in aging studies. PMID- 25110584 TI - BridgeDb app: unifying identifier mapping services for Cytoscape. AB - The BridgeDb app for Cytoscape allows users to map and annotate identifiers of genes, proteins and metabolites in the context of biological networks. The app greatly simplifies the identifier mapping process in Cytoscape by providing a unified interface to different mapping resources and services. The app also provides a programming interface via Cytoscape Commands that can be utilized for identifier mapping by other Cytoscape apps. In this article we provide a technical guide to the BridgeDb app for mapping identifiers in Cytoscape. PMID- 25110585 TI - Global burden, distribution, and interventions for infectious diseases of poverty. AB - Infectious diseases of poverty (IDoP) disproportionately affect the poorest population in the world and contribute to a cycle of poverty as a result of decreased productivity ensuing from long-term illness, disability, and social stigma. In 2010, the global deaths from HIV/AIDS have increased to 1.5 million and malaria mortality rose to 1.17 million. Mortality from neglected tropical diseases rose to 152,000, while tuberculosis killed 1.2 million people that same year. Substantial regional variations exist in the distribution of these diseases as they are primarily concentrated in rural areas of Sub-Saharan Africa, Asia, and Latin America, with geographic overlap and high levels of co-infection. Evidence-based interventions exist to prevent and control these diseases, however, the coverage still remains low with an emerging challenge of antimicrobial resistance. Therefore, community-based delivery platforms are increasingly being advocated to ensure sustainability and combat co-infections. Because of the high morbidity and mortality burden of these diseases, especially in resource-poor settings, it is imperative to conduct a systematic review to identify strategies to prevent and control these diseases. Therefore, we attempted to evaluate the effectiveness of one of these strategies, that is community-based delivery for the prevention and treatment of IDoP. In this paper, we describe the burden, epidemiology, and potential interventions for IDoP. In subsequent papers of this series, we describe the analytical framework and the methodology used to guide the systematic reviews, and report the findings and interpretations of our analyses of the impact of community-based strategies on individual IDoPs. PMID- 25110586 TI - Likelihoods for fixed rank nomination networks. AB - Many studies that gather social network data use survey methods that lead to censored, missing, or otherwise incomplete information. For example, the popular fixed rank nomination (FRN) scheme, often used in studies of schools and businesses, asks study participants to nominate and rank at most a small number of contacts or friends, leaving the existence of other relations uncertain. However, most statistical models are formulated in terms of completely observed binary networks. Statistical analyses of FRN data with such models ignore the censored and ranked nature of the data and could potentially result in misleading statistical inference. To investigate this possibility, we compare Bayesian parameter estimates obtained from a likelihood for complete binary networks with those obtained from likelihoods that are derived from the FRN scheme, and therefore accommodate the ranked and censored nature of the data. We show analytically and via simulation that the binary likelihood can provide misleading inference, particularly for certain model parameters that relate network ties to characteristics of individuals and pairs of individuals. We also compare these different likelihoods in a data analysis of several adolescent social networks. For some of these networks, the parameter estimates from the binary and FRN likelihoods lead to different conclusions, indicating the importance of analyzing FRN data with a method that accounts for the FRN survey design. PMID- 25110587 TI - Aqueous interleukin-6 levels are superior to vascular endothelial growth factor in predicting therapeutic response to bevacizumab in age-related macular degeneration. AB - Objective. To prospectively evaluate the effect of intravitreal bevacizumab on aqueous levels of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with exudative age-related macular degeneration (AMD) and correlate clinical outcomes with cytokine levels. Methods. 30 eyes of 30 patients with exudative AMD underwent intravitreal injection of bevacizumab three times at monthly intervals. The aqueous samples prior to the 1st injection (baseline) and 3rd injection were analyzed for VEGF and IL-6 levels. Subjects were subgrouped based upon change in the central subfield (CSF) macular thickness on SD-OCT at 8 weeks. Group 1 included patients (n = 14) with a decrease in CSF thickness greater than 10% from the baseline (improved group). Group 2 included patients (n = 16) who had a decrease in CSF thickness 10% or less (treatment-resistant). Results. In subgroup analysis, in both groups 1 and 2 patients, compared to aqueous VEGF, aqueous IL-6 levels showed a better correlation with CSF thickness on SD-OCT (r = 0.72 and 0.71, resp.). Conclusions. Aqueous IL-6 may be an important marker of treatment response or resistance in wet macular degeneration. Future therapeutic strategies may include targeted treatment against both VEGF and IL-6, in patients who do not respond to anti-VEGF treatment alone. PMID- 25110588 TI - Construct validity and reliability of the adult rejection sensitivity questionnaire: a comparison of three factor models. AB - Objectives and Methods. The aim of the study was to investigate the construct validity of the ARSQ. Methods. The ARSQ and self-report measures of depression, anxiety, and hopelessness were administered to 774 Italian adults, aged 18 to 64 years. Results. Structural equation modeling indicated that the factor structure of the ARSQ can be represented by a bifactor model: a general rejection sensitivity factor and two group factors, expectancy of rejection and rejection anxiety. Reliability of observed scores was not satisfactory: only 44% of variance in observed total scores was due to the common factors. The analyses also indicated different correlates for the general factor and the group factors. Limitations. We administered an Italian version of the ARSQ to a nonclinical sample of adults, so that studies which use clinical populations or the original version of the ARSQ could obtain different results from those presented here. Conclusion. Our results suggest that the construct validity of the ARSQ is disputable and that rejection anxiety and expectancy could bias individuals to readily perceive and strongly react to cues of rejection in different ways. PMID- 25110589 TI - Antifungal susceptibility patterns, in vitro production of virulence factors, and evaluation of diagnostic modalities for the speciation of pathogenic Candida from blood stream infections and vulvovaginal candidiasis. AB - Candida spp. have emerged as successful pathogens in both invasive and mucosal infections. Varied virulence factors and growing resistance to antifungal agents have contributed to their pathogenicity. We studied diagnostic accuracy of HiCrome Candida Differential Agar and Vitek 2 Compact system for identification of Candida spp. in comparison with species-specific PCR on 110 clinical isolates of Candida from blood stream infections (54, 49%) and vulvovaginal candidiasis (56, 51%). C. albicans (61%) was the leading pathogen in VVC, while C. tropicalis (46%) was prominent among BSIs. HiCrome Agar and Vitek 2 Compact had good measures of agreement (kappa) 0.826 and 0.895, respectively, in comparison with PCR. We also tested these isolates for in vitro production of proteinase, esterase, phospholipases, and biofilms. Proteinase production was more among invasive isolates (P = 0.017), while phospholipase production was more among noninvasive isolates (P = 0.001). There was an overall increase in the production of virulence factors among non-albicans Candida. Identification of clinical isolates of Candida up to species level either by chromogenic agar or by Vitek 2 Compact system should be routinely done to choose appropriate therapy. PMID- 25110590 TI - External rotator sparing with posterior acetabular fracture surgery: does it change outcome? AB - This study analyses the results of the treatment with external rotator sparing approach in acetabular fractures to determine whether muscle sparing has a positive impact on functional outcome. 20 patients with a mean age of 45.9 years (range: 26-64) that had been treated for displaced acetabular fractures were included in this series. Short Musculoskeletal Function Assessment (SMFA) questionnaire and hip muscle strength measurement were done at the 24-month of follow-up period. The radiographic results at the final followup were excellent in 9 hips (45%), good in 6 hips (30%), fair in 4 hips (20%), and poor in one hip (5%) according to the criteria developed by Matta. The average SMFA score for all of the patients was 18.3 (range: 0-55.4). The mean dysfunctional and bother indexes were 17.2 and 20.6, respectively. The overall muscle strength deficit was 11.8%. The greatest loss of strength was in internal rotation. In patients with better postoperative reduction quality of acetabular fracture, peak torque, and maximum work of hip flexion, extension and also internal rotation maximum work deficit were significantly lower (P < 0.05). Accurate initial reduction and longer postoperative muscle strengthening exercise programs seem critical to decrease postoperative hip muscle weakness after acetabular fractures. PMID- 25110591 TI - Partial facetectomy for lumbar foraminal stenosis. AB - Background. Several different techniques exist to address the pain and disability caused by isolated nerve root impingement. Failure to adequately decompress the lumbar foramen may lead to failed back surgery syndrome. However, aggressive treatment often causes spinal instability or may require fusion for satisfactory results. We describe a novel technique for decompression of the lumbar nerve root and demonstrate its effectiveness in relief of radicular symptoms. Methods. Partial facetectomy was performed by removal of the medial portion of the superior facet in patients with lumbar foraminal stenosis. 47 patients underwent the procedure from 2001 to 2010. Those who demonstrated neurogenic claudication without spinal instability or central canal stenosis and failed conservative management were eligible for the procedure. Functional level was recorded for each patient. These patients were followed for an average of 3.9 years to evaluate outcomes. Results. 27 of 47 patients (57%) reported no back pain and no functional limitations. Eight of 47 patients (17%) reported moderate pain, but had no limitations. Six of 47 patients (13%) continued to experience degenerative symptoms. Five of 47 patients (11%) required additional surgery. Conclusions. Partial facetectomy is an effective means to decompress the lumbar nerve root foramen without causing spinal instability. PMID- 25110594 TI - Myocardial Rupture following Carbon Monoxide Poisoning. AB - We present the first case of severe cardiotoxicity of carbon monoxide leading to myocardial rupture and fatal outcome. 83-year-old woman was hospitalized 4 hours after the fire in her house with no respiratory or cardiac symptoms. After two days, she has suffered sudden collapse leading to cardiac arrest. Postmortem examination revealed intramural haemorrhage with myocardial rupture at the apex of the left ventricle. Minimal stenosis was noted in the proximal coronary arteries with no evidence of distal occlusion or any other long-standing heart disease. This case supports recommendations for targeted cardiovascular investigations in cases of CO poisoning. PMID- 25110595 TI - Informed consent in otolaryngologic surgery: case scenario from a nigerian specialist hospital. AB - Informed consent is a foundational concept necessary for ethical conduct of clinical research and practice. It is a technical tool that shifts the autonomy to decide whether a medical procedure should be performed-from the doctor to the patient. However there is an ongoing discussion in bioethical circles on the level of comprehension of the informed consent process by the patients and research participants. We present this case vignette and the discussion afterwards to explore the question of to what extent a patient comprehends the information given to him/her before a surgical procedure is carried out. In other words, the question being asked here is how informed is informed consent in the context of oto-laryngological practice. PMID- 25110592 TI - Behavioral improvement and regulation of molecules related to neuroplasticity in ischemic rat spinal cord treated with PEDF. AB - Pigment epithelium derived factor (PEDF) exerts trophic actions to motoneurons and modulates nonneuronal restorative events, but its effects on neuroplasticity responses after spinal cord (SC) injury are unknown. Rats received a low thoracic SC photothrombotic ischemia and local injection of PEDF and were evaluated behaviorally six weeks later. PEDF actions were detailed in SC ventral horn (motor) in the levels of the lumbar central pattern generator (CPG), far from the injury site. Molecules related to neuroplasticity (MAP-2), those that are able to modulate such event, for instance, neurotrophic factors (NT-3, GDNF, BDNF, and FGF-2), chondroitin sulfate proteoglycans (CSPG), and those associated with angiogenesis and antiapoptosis (laminin and Bcl-2) and Eph (receptor)/ephrin system were evaluated at cellular or molecular levels. PEDF injection improved motor behavioral performance and increased MAP-2 levels and dendritic processes in the region of lumbar CPG. Treatment also elevated GDNF and decreased NT-3, laminin, and CSPG. Injury elevated EphA4 and ephrin-B1 levels, and PEDF treatment increased ephrin A2 and ephrins B1, B2, and B3. Eph receptors and ephrins were found in specific populations of neurons and astrocytes. PEDF treatment to SC injury triggered neuroplasticity in lumbar CPG and regulation of neurotrophic factors, extracellular matrix molecules, and ephrins. PMID- 25110596 TI - Axillary metastasis from an occult tubal serous carcinoma in a patient with ipsilateral breast carcinoma: a potential diagnostic pitfall. AB - Axillary nodal metastasis from a nonmammary neoplasia is much rarer than diseases associated with a primary breast carcinoma. However, this has to be considered in the differential diagnosis of nodal disease in patients with a history of breast cancer. Here, we report the case of a 73-year-old female with a past medical history of breast cancer, presenting with an ipsilateral axillary metastatic carcinoma. The immunohistochemical profile of the metastatic lesion was consistent with a high grade serous carcinoma. After undergoing a total abdominal hysterectomy and salpingo-oophorectomy, thorough pathological examination revealed two microscopic foci of serous carcinoma in the right fallopian tube, not detectable by preoperative magnetic resonance imaging. In this context, the poorly differentiated appearance of the metastatic tumor and positive staining for estrogen receptor, might lead to a misdiagnosis of metastatic breast carcinoma. As the therapeutic implications differ, it is important for the pathologist to critically assess axillary lymph node metastases, even in patients with a past history of ipsilateral breast carcinoma and no other known primary tumors. PMID- 25110593 TI - Adult hippocampal neurogenesis in Parkinson's disease: impact on neuronal survival and plasticity. AB - In Parkinson's disease (PD) and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research. PMID- 25110597 TI - Nodular Lymphocyte Predominant Hodgkin Lymphoma versus T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Diagnostic Challenge. AB - Lymphomas with overlapping histological features of two distinct entities cause difficulty in classification. Their classification is of particular significance when the two alternatives require different treatment modalities. We present a diagnostically challenging case of a nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) with features of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL). Our patient is a 39-year-old woman who presented with painless subclavicular and axillary lymphadenopathy. The biopsied lymph node showed diffuse architectural effacement and scattered large neoplastic cells with large irregular nuclei and prominent nucleoli. These cells were positive for CD20 and Bcl-6 and negative for CD15, CD30, IgD, and Bcl-2. The background cells were predominantly T lymphocytes, whereas B cells were markedly depleted. The lymph node was interpreted as NLPHL, consistent with THRLBCL-like variant. NLPHL, especially THRLBC-like variant, and de novo THRLBCL are characterized by significant morphologic and immunophenotypic overlap. Our case demonstrates a rare predominance of background T-cells in NLPHL and emphasizes the importance of thorough evaluation of multiple morphologic and immunophenotypic features as an essential approach for arriving at the correct diagnosis. PMID- 25110598 TI - Sarcoidosis incidentally diagnosed: a case report. AB - Sarcoidosis is a chronic, granulomatous condition with unknown cause. Because most of the patients are free of clinical symptoms, sarcoidosis should be considered in differential diagnosis if noncaseous granuloma is noted in biopsies, performed for other reasons. With no clinical symptoms, our patient was diagnosed with sarcoidosis upon identifying noncaseous granuloma in the lymph node biopsy material collected during the laparoscopic operation, performed for gallbladder polyp. PMID- 25110599 TI - Rapidly destructive inflammatory arthritis of the hip. AB - Rapidly destructive coxarthrosis (RDC) is a rare syndrome that involves aggressive hip joint destruction within 6-12 months of symptom onset with no single diagnostic laboratory, pathological, or radiographic finding. We report an original case of RDC as an initial presentation of seronegative rheumatoid arthritis (RA) in a 57-year-old Caucasian woman presenting with 6 months of progressive right groin pain and no preceding trauma or chronic steroid use. Over 5 months, she was unable to ambulate and plain films showed complete resorption of the right femoral head and erosion of the acetabulum. There were inflammatory features seen on computed tomography (CT) and magnetic resonance imaging (MRI). She required a right total hip arthroplasty, but arthritis in other joints showed improvement with triple disease modifying antirheumatic drugs (DMARD) therapy and almost complete remission with the addition of adalimumab. We contrast our case of RDC as an initial presentation of RA to 8 RDC case reports of patients with established RA. Furthermore, this case highlights the importance of obtaining serial imaging to evaluate a patient with persistent hip symptoms and rapid functional deterioration. PMID- 25110600 TI - Treatment resistant severe digital ischemia associated with antiphospholipid syndrome in a male patient with systemic sclerosis. AB - We report the case of a male patient with limited cutaneous systemic sclerosis (SSc) that was complicated with severe digital ischemia, resistant to medical treatment. Due to the lack of treatment response, further laboratory and imaging studies were conducted. Findings were compatible with antiphospholipid syndrome and oral warfarin was added to the treatment regimen. After successful anticoagulation no further recurrences of digital ischemia were seen. An underlying etiology in SSc patients with treatment resistant digital ischemic necrosis should be suspected for accompanying antiphospholipid syndrome (APS). PMID- 25110601 TI - Laparoscopic Right Hemicolectomy in an Automated Peritoneal Dialysis Patient without Removal of the PD Catheter: A Case Report. AB - Introduction. Laparotomy in patients on peritoneal dialysis (PD) is associated with an increased risk of morbidity. Furthermore, standard protocol recommends removal of the PD catheter when surgery on the intestine is required. As far as we are aware, this is the first case report of laparoscopic right hemicolectomy in a patient on automated PD where the PD catheter was left in situ. Case Report. A 61-year-old man man on APD who presented with a caecal carcinoma was stabilised on temporary haemodialysis (HD) prior to undergoing a laparoscopic right hemicolectomy without removal of the PD catheter. He made an uneventful recovery and APD was resumed successfully 2 weeks after surgery. Discussion. PD patients undergoing intra-abdominal surgery are at increased risk of complications. While the benefits of laparoscopic surgery in the standard surgical population are well established, there is limited experience of the technique in PD patients. Possible advantages could theoretically be early resumption of PD as well as less PD failure due to the formation of adhesions. Conclusion. Our experience with this case indicates that laparoscopic right hemicolectomy in a background of PD can be undertaken without removal of the PD catheter and is associated with early resumption of PD. PMID- 25110602 TI - Incidental Phaeochromocytoma on Staging PET-CT in a Patient with a Sigmoid Tumour and Situs Inversalis Totalis. AB - An adrenal "incidentaloma" is defined as an unexpected finding on radiological imaging performed for unrelated indications. Improvements in radiological technology have seen a dramatic increase in this phenomenon. We report the unique case of a 60-year-old female presenting with a 6-month history of abdominal pain, altered bowel habit, and rectal bleeding. Her past medical history included situs inversus totalis and a patent ductus arteriosus. Colonoscopy revealed an ulcerated tumour in her sigmoid colon. Staging PET-CT confirmed a sigmoid tumour and also identified a large heterogenous enhancing FDG-avid right adrenal mass. Biochemical testing/MIBG imaging confirmed a right adrenal phaeochromocytoma. Hypertension was controlled and excision was performed via a transperitoneal laparoscopic adrenalectomy, in the left lateral decubitus position. Uniquely, liver retraction was not required due to its position in the left hypochondrium. Histology confirmed a benign 46 mm phaeochromocytoma. Subsequent uncomplicated sigmoid colectomy/right salpingo-oophorectomy for a locally advanced colonic tumour was performed with adjuvant chemotherapy. This case highlights the importance of accurately identifying functioning adrenal tumours before elective surgery as undiagnosed phaeochromocytomas carry significant intraoperative morbidity/mortality. Right adrenalectomy was made easier in this patient by the liver's unique position. Uncomplicated colorectal resection was made possible by combined preoperative functional/anatomical imaging. PMID- 25110603 TI - Recurrent volvulus of an ileal pouch requiring repeat pouchopexy: a lesson learnt. AB - Introduction. Restorative surgery for ulcerative colitis with ileal pouch anal anastomosis (IPAA) is frequently accompanied by complications. Volvulus of the ileal pouch is one of the most rarely reported late complications and to our knowledge no report exists on reoperative surgery for this condition. Case Report. A 58-year-old woman who previously had undergone restorative proctocolectomy due to ulcerative colitis with an IPAA presented with volvulus of the pouch. She was operated with a single row pouchopexy to the presacral fascia. Two months later she returned with a recurrent volvulus. At reoperation, the pouch was found to have become completely detached from the fascia. A new pexy was made by firmly anchoring the pouch with two rows of sutures to the presacral fascia as well as with sutures to the lateral pelvic walls. At follow-up after five months she was free of symptoms. Conclusion. This first report ever on reoperative surgery for volvulus of a pelvic pouch indicates that a single row pouchopexy might be insufficient for preventing retwisting. Several rows seem to be needed. PMID- 25110604 TI - Laparoscopic-assisted resection of jejunojejunal intussusception caused by a juvenile polyp in an adult. AB - Most bowel intussusceptions in adults have a leading point. However, there have been few reports of jejunojejunal intussusception secondary to a solitary juvenile polyp in adult. We report herein the case of a 19-year-old female with a solitary juvenile polyp in the jejunum causing intussusception. Laparoscopic assisted reduction and segmental resection of the jejunum were successfully done for the patient. PMID- 25110605 TI - Successful management of repetitive urinary obstruction and anuria caused by double j stent calculi formation after renal transplantation. AB - This report firstly describes an extremely rare case of repetitive double J stent calculi formation after renal transplantation caused by the antihyperparathyroidism (HPT) drug calcitriol. In 2012, a woman initially presented to our hospital for anuria with lower abdominal pain. She was diagnosed with allograft hydronephrosis and double J stents obstruction by calculi formation after transplantation and treated with triplicate stents replacements in another hospital without clinical manifestations improvements. Through detailed exploration of medical history, we conclude that the abnormal calculi formation is due to the calcitriol (1,25-dihydroxyvitamin D3) administration, a drug which can increase renal tubular reabsorption of calcium for treating posttransplant HPT bone disease. After discontinuing calcitriol, the patient was stone-free and had a good recovery without severe complications during the 9 month follow-up. Our novel findings may provide an important clue and approach to managing formidable repetitive double J stent calculi formation in the clinical trial. PMID- 25110606 TI - Iatrogenic salt water drowning and the hazards of a high central venous pressure. AB - Current teaching and guidelines suggest that aggressive fluid resuscitation is the best initial approach to the patient with hemodynamic instability. The source of this wisdom is difficult to discern, however, Early Goal Directed therapy (EGDT) as championed by Rivers et al. and the Surviving Sepsis Campaign Guidelines appears to have established this as the irrefutable truth. However, over the last decade it has become clear that aggressive fluid resuscitation leading to fluid overload is associated with increased morbidity and mortality across a diverse group of patients, including patients with severe sepsis as well as elective surgical and trauma patients and those with pancreatitis. Excessive fluid administration results in increased interstitial fluid in vital organs leading to impaired renal, hepatic and cardiac function. Increased extra-vascular lung water (EVLW) is particularly lethal, leading to iatrogenic salt water drowning. EGDT and the Surviving Sepsis Campaign Guidelines recommend targeting a central venous pressure (CVP) > 8 mmHg. A CVP > 8 mmHg has been demonstrated to decrease microcirculatory flow, as well as renal blood flow and is associated with an increased risk of renal failure and death. Normal saline (0.9% salt solution) as compared to balanced electrolyte solutions is associated with a greater risk of acute kidney injury and death. This paper reviews the adverse effects of large volume resuscitation, a high CVP and the excessive use of normal saline. PMID- 25110607 TI - Managing sarcopenia and its related-fractures to improve quality of life in geriatric populations. AB - Sarcopenia, an aging-induced generalized decrease in muscle mass, strength, and function, is known to affect elderly individuals by decreasing mobile function and increasing frailty and imbalance that lead to falls and fragile fractures. Sarcopenia is a known risk factor for osteoporotic fractures, infections, and early death in some specific situations. The number of patients with sarcopenia is estimated to increase to 500 million people in the year 2050. Sarcopenia is believed to be caused by multiple factors such as disuse, malnutrition, age related cellular changes, apoptosis, and genetic predisposition; however, this remains to be determined. Various methods have been developed, but no safe or effective treatment has been found to date. This paper is a review on the association between sarcopenia and its related-fractures and their diagnoses and management methods to prevent fractures. PMID- 25110609 TI - Accelerated aging in schizophrenia patients: the potential role of oxidative stress. AB - Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia. PMID- 25110610 TI - mTOR Signaling from Cellular Senescence to Organismal Aging. AB - The TOR (target of rapamycin) pathway has been convincingly shown to promote aging in various model organisms. In mice, inhibiting mTOR (mammalian TOR) by rapamycin treatment later in life can significantly extend lifespan and mitigate multiple age-related diseases. However, the underlying mechanisms are poorly understood. Cellular senescence is strongly correlated to organismal aging therefore providing an attractive model to examine the mechanisms by which mTOR inhibition contributes to longevity and delaying the onset of related diseases. In this review, we examine the connections between mTOR and cellular senescence and discuss how understanding cellular senescence on the aspect of mTOR signaling may help to fully appreciate its role in the organismal aging. We also highlight the opposing roles of senescence in various human diseases and discuss the caveats in interpreting the emerging experimental data. PMID- 25110611 TI - Effects of living at higher altitudes on mortality: a narrative review. AB - Beside genetic and life-style characteristics environmental factors may profoundly influence mortality and life expectancy. The high altitude climate comprises a set of conditions bearing the potential of modifying morbidity and mortality of approximately 400 million people who are permanently residing at elevations above 1500 meters. However, epidemiological data on the effects of high altitude living on mortality from major diseases are inconsistent probably due to differences in ethnicity, behavioral factors and the complex interactions with environmental conditions. The available data indicate that residency at higher altitudes are associated with lower mortality from cardiovascular diseases, stroke and certain types of cancer. In contrast mortality from COPD and probably also from lower respiratory tract infections is rather elevated. It may be argued that moderate altitudes are more protective than high or even very high altitudes. Whereas living at higher elevations may frequently protect from development of diseases, it could adversely affect mortality when diseases progress. Corroborating and expanding these findings would be helpful for optimization of medical care and disease management in the aging residents of higher altitudes. PMID- 25110608 TI - Metabolic disturbances in diseases with neurological involvement. AB - Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alterations, exogenous toxins or buildup of toxic metabolites. In this review we shall discuss some metabolic alterations related to the pathophysiology of diseases with neurological involvement and aging process. These findings may help identifying early disease biomarkers and lead to more effective therapies to improve the quality of life of the patients affected by these devastating illnesses. PMID- 25110612 TI - Nothobranchius as a model for aging studies. A review. AB - In recent decades, the increase in human longevity has made it increasingly important to expand our knowledge on aging. To accomplish this, the use of animal models is essential, with the most common being mouse (phylogenetically similar to humans, and a model with a long life expectancy) and Caenorhabditis elegans (an invertebrate with a short life span, but quite removed from us in evolutionary terms). However, some sort of model is needed to bridge the differences between those mentioned above, achieving a balance between phylogenetic distance and life span. Fish of the genus Nothobranchius were suggested 10 years ago as a possible alternative for the study of the aging process. In the meantime, numerous studies have been conducted at different levels: behavioral (including the study of the rest-activity rhythm), populational, histochemical, biochemical and genetic, among others, with very positive results. This review compiles what we know about Nothobranchius to date, and examines its future prospects as a true alternative to the classic models for studies on aging. PMID- 25110613 TI - Estimation of Heterogeneity in Diagnostic Parameters of Age-related Diseases. AB - The heterogeneity of parameters is a ubiquitous biological phenomenon, with critical implications for biological systems functioning in normal and diseased states. We developed a method to estimate the level of objects set heterogeneity with reference to particular parameters and applied it to type II diabetes and heart disease, as examples of age-related systemic dysfunctions. The Friedman test was used to establish the existence of heterogeneity. The Newman-Keuls multiple comparison method was used to determine clusters. The normalized Shannon entropy was used to provide the quantitative evaluation of heterogeneity. There was obtained an estimate for the heterogeneity of the diagnostic parameters in healthy subjects, as well as in heart disease and type II diabetes patients, which was strongly related to their age. With aging, as with the diseases, the level of heterogeneity (entropy) was reduced, indicating a formal analogy between these phenomena. The similarity of the patterns in aging and disease suggested a kind of "early aging" of the diseased subjects, or alternatively a "disease-like" aging process, with reference to these particular parameters. The proposed method and its validation on the chronic age-related disease samples may support a way toward a formal mathematical relation between aging and chronic diseases and a formal definition of aging and disease, as determined by particular heterogeneity (entropy) changes. PMID- 25110614 TI - Beyond IC50s: Towards Robust Statistical Methods for in vitro Association Studies. AB - Cell line cytotoxicity assays have become increasingly popular approaches for genetic and genomic studies of differential cytotoxic response. There are an increasing number of success stories, but relatively little evaluation of the statistical approaches used in such studies. In the vast majority of these studies, concentration response is summarized using curve-fitting approaches, and then summary measure(s) are used as the phenotype in subsequent genetic association studies. The curve is usually summarized by a single parameter such as the curve's inflection point (e.g. the EC/IC50). Such modeling makes major assumptions and has statistical limitations that should be considered. In the current review, we discuss the limitations of the EC/IC50 as a phenotype in association studies, and highlight some potential limitations with a simulation experiment. Finally, we discuss some alternative analysis approaches that have been shown to be more robust. PMID- 25110616 TI - Creating a safe space to learn: The significant role of graduate students in fostering educational engagement and aspirations among urban youth. PMID- 25110615 TI - Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System: SVCT2 versus Gluts. AB - Vitamin C is an essential micronutrient in the human diet; its deficiency leads to a number of symptoms and ultimately death. After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation. In this review, we will compare the molecular and structural aspects of vitamin C and glucose transporters and their expression in endothelial or choroid plexus cells, which form part of the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, respectively. Additionally, we will describe SVCT and GLUT expression in different cells of the brain as well as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region. Finally, we will describe vitamin C recycling in the brain, which is mediated by a metabolic interaction between astrocytes and neurons, and the role of the "bystander effect" in the recycling mechanism of vitamin C in both normal and pathological conditions. PMID- 25110618 TI - Tuberculous meningitis: Diagnostic and therapeutic challenges. AB - Neurologists are often the first medical providers to evaluate patients with possible infectious meningitis. Knowledge of the clinical presentations and cerebrospinal fluid, microbiologic, and neuroimaging findings for different etiologies is essential to make a prompt diagnosis and initiate appropriate treatment. Tuberculosis is a common cause of meningitis in developing countries with a high prevalence of pulmonary tuberculosis. However, tuberculosis affects populations in every country and all neurologists need to be vigilant for possible cases of tuberculous meningitis presenting to their medical facilities. This article discusses the challenges of diagnosing and treating tuberculous meningitis and highlights recent advances in diagnostic technology. PMID- 25110617 TI - Fertility Preservation for Prepubertal Girls: Update and Current Challenges. AB - With increasing rates of diagnosis of childhood cancers and the evolution of more effective treatment options resulting in prolonged life spans, fertility preservation counseling is an integral component of the discussion at the time of diagnosis of childhood cancers. The primary fertility preservation option that exists for prepubertal girls is ovarian tissue cryopreservation. Although ovarian tissue cryopreservation is still considered to be experimental in nature, live births have resulted from orthotopic tissue transplantation. Fertility preservation should be offered to all prepubertal girls at high-risk for premature ovarian failure as a result of gonadotoxic treatment. Ethical and legal questions surrounding these issues must be considered as more and more pediatric patients pursue fertility preservation. PMID- 25110619 TI - Diagnosis and management of acute encephalitis: A practical approach. AB - Encephalitis results in considerable morbidity and mortality in the United States and worldwide. Neurologists are often consulted or directly care for patients with encephalitis admitted to the hospital and must be able to discriminate between encephalitis and the many conditions that mimic it. Moreover, neurologists must be familiar with the myriad causes of encephalitis in order to develop a practical approach to diagnostic testing and treatment. An understanding of recent advances in management, particularly with respect to autoimmune etiologies and critical care approaches, is equally important. Here, we summarize a general approach to the care of adult patients with encephalitis. PMID- 25110620 TI - Dementia in MS complicated by coexistent Alzheimer disease: Diagnosis premortem and postmortem. AB - Distinguishing dementia due to multiple sclerosis (MS) from that of an accompanying neurodegenerative dementia coexisting with MS has been difficult. The recent introduction of Alzheimer disease (AD) biomarkers of amyloid-beta and neuronal degeneration has improved diagnosis of AD premortem. We describe 3 patients with MS with coexisting AD, 1 diagnosed at autopsy before AD biomarkers were available and 2 diagnosed premortem by decreased CSF amyloid-beta1-42/tau index, MRI, and 18F-flourodeoxyglucose-PET patterns. AD biomarkers may be of diagnostic value in selected patients with severe dementia and MS. PMID- 25110621 TI - Neurology goes global: Opportunities in international health. AB - In recent years, the need for additional neurologists and neurologic expertise in many low- and middle-income countries (LMIC) has become more apparent. Many organizations are committed to this unmet need, but the scope of the problem remains mostly underappreciated. Neurologists may be skeptical about their value in resource-limited settings, yet we are critically needed and can have a marked effect. International experiences, however, must be carried out in ethical, informed, and sustainable ways in tandem with local health care providers when possible. We present a brief overview of critical issues in global neurology, the importance of focusing on benefits to the LMIC, and options for volunteer opportunities in clinical service, education, research, and disaster relief. Finally, we offer practical pointers and resources for planning these experiences. PMID- 25110622 TI - State neurologic societies and the AAN: Strengthening neurology for the future. AB - This report considers the recommendations of the State Society Task Force (SSTF), which evaluated how the relationship between the American Academy of Neurology (AAN) and neurologic societies of individual states can foster the care of patients with neurologic diseases. The task force also evaluated the role of state neurosociety and state medical society interactions in supporting the profession of neurology. The SSTF recommended that the AAN expand current support services to state neurosocieties and foster additional neurosociety development. Specific services to be considered by the AAN include online combined AAN/state neurosociety dues payment and enhanced Web support. The role of the AAN as a liaison between state neurosocieties and state medical societies is important to facilitate state level advocacy for neurology. PMID- 25110623 TI - Acute HIV infection presenting as fulminant meningoencephalitis with massive CSF viral replication. AB - A 22-year-old man presented to the emergency department with 10 days of malaise, generalized rash, sore throat, oral ulcers, headache, nausea, and vomiting. On examination he had fever (101.5 degrees F), hepatosplenomegaly, generalized maculopapular rash, and lymphadenopathy. He rapidly became obtunded, requiring intubation. Initial laboratory studies showed mild transaminitis, increased lactate dehydrogenase, and 4,600 leukocytes per MUL with 61% bands and 18% lymphocytes. Bacterial and fungal blood cultures were negative as well as a rapid HIV test, additional serologies (including rapid plasma reagin and Treponema pallidum particle agglutination), quantitative PCRs (for viruses other than HIV), and urine and blood toxicology. CSF, on hospital day 4, showed a lymphocytic pleocytosis (total leukocytes: 100), high protein, borderline hypoglycorrhachia, and negative Gram stain and culture. Brain MRI revealed no meningeal enhancement or masses. EEG revealed no epileptiform activity. Flow cytometry on bone marrow biopsy and CSF found no evidence of malignancy; neither did an excisional lymph node biopsy (figure 1). An immunofluorescent assay test for HIV returned inconclusive and a Western blot detected HIV gp120/gp160 bands. Quantitative HIV RNA PCR was 1.4 * 106 copies/mL in plasma and in CSF exceeded the upper limit of quantitation (107 copies/mL) (figure 2). PMID- 25110624 TI - Applications of Brain-Machine Interface Systems in Stroke Recovery and Rehabilitation. AB - Stroke is a leading cause of disability, significantly impacting the quality of life (QOL) in survivors, and rehabilitation remains the mainstay of treatment in these patients. Recent engineering and technological advances such as brain machine interfaces (BMI) and robotic rehabilitative devices are promising to enhance stroke neu-rorehabilitation, to accelerate functional recovery and improve QOL. This review discusses the recent applications of BMI and robotic assisted rehabilitation in stroke patients. We present the framework for integrated BMI and robotic-assisted therapies, and discuss their potential therapeutic, assistive and diagnostic functions in stroke rehabilitation. Finally, we conclude with an outlook on the potential challenges and future directions of these neurotechnologies, and their impact on clinical rehabilitation. PMID- 25110625 TI - The Immune System and AMD. AB - Age related macular degeneration (AMD) is a complex, multifactorial disease that has yet to be completely understood. Significant efforts in the basic and clinical sciences have unveiled numerous areas which appear to be critical in the pathogenesis of this disease. The alternative complement pathway, immune cell activation, and autoimmunity are all emerging as important themes to the suspected immunologic origins of this disease. Advancement toward a complete understanding of these processes is important in development of new techniques for disease monitoring and treatment. PMID- 25110626 TI - Habitual exercise plus dietary supplementation with milk fat globule membrane improves muscle function deficits via neuromuscular development in senescence accelerated mice. AB - We examined the effects of habitual exercise plus nutritional intervention through consumption of milk fat globule membrane (MFGM), a milk component, on aging-related deficits in muscle mass and function in senescence-accelerated P1 mice. Combining wheel-running and MFGM (MFGMEx) intake significantly attenuated age-related declines in quadriceps muscle mass (control: 318 +/- 6 mg; MFGMEx: 356 +/- 9 mg; P < 0.05) and in contractile force (1.4-fold and 1.5-fold higher in the soleus and extensor digitorum longus muscles, respectively). Microarray analysis of genes in the quadriceps muscle revealed that MFGMEx stimulated neuromuscular development; this was supported by significantly increased docking protein-7 (Dok-7) and myogenin mRNA expression. Treatment of differentiating myoblasts with MFGM-derived phospholipid or sphingolipid fractions plus mechanical stretching also significantly increased Dok-7 mRNA expression. These findings suggest that habitual exercise plus dietary MFGM improves muscle function deficits through neuromuscular development, and that phospholipid and sphingolipid in MFGM contribute to its physiological actions. PMID- 25110627 TI - Effects of a pre-and post-workout protein-carbohydrate supplement in trained crossfit individuals. AB - PURPOSE: The purpose was to assess effects of a pre- and a post-workout protein carbohydrate supplement on CrossFit-specific performance and body composition. METHODS: In an open label randomized study, 13 male and 16 female trained Crossfit participants (mean +/- SD; age: 31.87 +/- 7.61 yrs, weight: 78.68 +/- 16.45 kg, percent body fat: 21.97 +/- 9.02) were assessed at 0 and 6 weeks for body composition, VO2max, Wingate peak (WPP) and mean power (WMP), in addition to sport-specific workouts (WOD1: 500 m row, 40 wall balls, 30 push-ups, 20 box jumps, 10 thrusters for time; WOD2: 15 minutes to complete an 800 m run "buy in", followed by as many rounds as possible (AMRAP) of 5 burpees, 10 Kettlebell swings, 15 air squats). The supplement (SUP) group consisted of 19 g of a pre workout drink (extracts of pomegranate, tart cherry, green and black tea) taken 30 minutes before and a post-workout protein (females: 20 g; males: 40 g) and carbohydrate (females: 40 g; males: 80 g) supplement consumed immediately after each workout. The control (CTL) group consumed only water one hour before or after workouts. Participants completed three (minimum) varied workouts per week at a CrossFit gym as typical to habitual training throughout the six week study. Data were analyzed by repeated measures ANOVA (p <0 .05), 95% Confidence Intervals, and Magnitude Inferences. RESULTS: There were no time * group interactions for body composition, WMP, or WOD1 based on ANOVA statistics. VO2MAX, WPP, and WOD2 results revealed that the pre/post supplements were likely beneficial after 95% Confidence Intervals and Magnitude Inferences analysis. CONCLUSION: The combination of proprietary supplements taken for 6 weeks may provide benefits during certain sport-specific performance in trained CrossFit athletes but not others. PMID- 25110628 TI - Approaches for the design of reduced toxicant emission cigarettes. AB - Cigarette smoking causes serious diseases through frequent and prolonged exposure to toxicants. Technologies are being developed to reduce smokers' toxicant exposure, including filter adsorbents, tobacco treatments and substitutes. This study examined the effect of modifications to filter ventilation, variations in cigarette circumference and active charcoal filter length and loading, as well as combinations of these features in a reduced-toxicant prototype (RTP) cigarette, on the yields of toxicants in cigarette smoke. An air-dilution mechanism, called split-tipping, was developed in which a band of porous paper in the centre of the filter tipping functions to minimise the loss of effective filter ventilation that occurs at the high flow rates encountered during human-smoking, and to facilitate the diffusional loss of volatile toxicants. As compared with conventional filter ventilation cigarettes, split-tipping reduced tar and volatile smoke constituent emissions under high flow rate machine-smoking conditions, most notably for products with a 1-mg ISO tar yield. Furthermore, mouth level exposure (MLE) to tar and nicotine was reduced among smokers of 1-mg ISO tar cigarettes in comparison to smokers of cigarettes with traditional filter ventilation. For higher ISO tar level cigarettes, however, there were no significant reductions in MLE. Smaller cigarette circumferences reduced sidestream toxicant yields and modified the balance of mainstream smoke chemistry with reduced levels of aromatic amines and benzo[a]pyrene but increased yields of formaldehyde. Smaller circumference cigarettes also had lower mainstream yields of volatile toxicants. Longer cigarette filters containing increased levels of high-activity carbon (HAC) showed reduced machine-smoking yields of volatile toxicants: with up to 97% removal for some volatile toxicants at higher HAC loadings. Split-tipping was combined with optimal filter length and cigarette circumference in an RTP cigarette that gave significantly lower mainstream (up to ~90%) and sidestream (predominately 20%-60%) smoke yields of numerous toxicants as compared with a commercial comparator cigarette under machine-smoking conditions. Significantly lower mainstream and sidestream smoke toxicant yields were observed for an RTP cigarette comprising several toxicant reducing technologies; these observations warrant further evaluation in clinical studies where real-world relevance can be tested using biomarkers of exposure and physiological effect. PMID- 25110629 TI - Pigeonpea genotypes influence parasitization preference and survival and development of the Helicoverpa armigera larval parasitoid, Campoletis chlorideae. AB - Studies were undertaken to identify pigeonpea, Cajanus cajan (L.) Millspaugh and the wild relative of pigeonpea, Cajanus scarabaeoides (L.) (accession ICPW 125,) genotypes that are hospitable to the pod borer, Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) larval parasitoid, Campoletis chlorideae Uchida (Hymenoptera: Ichneumonidae) for the management of this pest in pigeonpea based cropping systems. Percentage parasitization of the H. armigera larvae by the C. chlorideae females was greater under no-choice conditions than under multi-choice conditions because of forced parasitization under no-choice conditions. Lowest parasitization was recorded on the wild relative, ICPW 125, which may be due to long nonglandular hairs and low survival of H. armigera larvae. Parasitization of H. armigera larvae was greater under no-choice, dual-choice and/or multi-choice conditions on ICPL 87, ICPL 87119 and ICPL 87091, which are susceptible to H. armigera, than on the pod borer-resistant genotypes ICPL 332WR, ICPL 84060 and ICPB 2042; while survival and development of the parasitoid was better on H. armigera larvae fed on ICPL 87, ICPL 87119, LRG 41, ICP 7035 and ICPL 87091 than on ICPL 332WR, ICPL 84060, ICPB 2042 and ICPW 125. The genotypes ICPL 87, ICPL 87119, LRG 42 and ICPL 87091 that are hospitable to C. chloridae, are better suited for use in integrated pest management to minimize the losses due to H. armigera in pigeonpea. PMID- 25110630 TI - Isolation and enzyme bioprospection of endophytic bacteria associated with plants of Brazilian mangrove ecosystem. AB - The mangrove ecosystem is a coastal tropical biome located in the transition zone between land and sea that is characterized by periodic flooding, which confers unique and specific environmental conditions on this biome. In these ecosystems, the vegetation is dominated by a particular group of plant species that provide a unique environment harboring diverse groups of microorganisms, including the endophytic microorganisms that are the focus of this study. Because of their intimate association with plants, endophytic microorganisms could be explored for biotechnologically significant products, such as enzymes, proteins, antibiotics and others. Here, we isolated endophytic microorganisms from two mangrove species, Rhizophora mangle and Avicennia nitida, that are found in streams in two mangrove systems in Bertioga and Cananeia, Brazil. Bacillus was the most frequently isolated genus, comprising 42% of the species isolated from Cananeia and 28% of the species from Bertioga. However, other common endophytic genera such as Pantoea, Curtobacterium and Enterobacter were also found. After identifying the isolates, the bacterial communities were evaluated for enzyme production. Protease activity was observed in 75% of the isolates, while endoglucanase activity occurred in 62% of the isolates. Bacillus showed the highest activity rates for amylase and esterase and endoglucanase. To our knowledge, this is the first reported diversity analysis performed on endophytic bacteria obtained from the branches of mangrove trees and the first overview of the specific enzymes produced by different bacterial genera. This work contributes to our knowledge of the microorganisms and enzymes present in mangrove ecosystems. PMID- 25110631 TI - Different pioneer plant species select specific rhizosphere bacterial communities in a high mountain environment. AB - The rhizobacterial communities of 29 pioneer plants belonging to 12 species were investigated in an alpine ecosystem to assess if plants from different species could select for specific rhizobacterial communities. Rhizospheres and unvegetated soils were collected from a floristic pioneer stage plot at 2,400 m a.s.l. in the forefield of Weisskugel Glacier (Matsch Valley, South Tyrol, Italy), after 160 years of glacier retreat. To allow for a culture-independent perspective, total environmental DNA was extracted from both rhizosphere and bare soil samples and analyzed by Automated Ribosomal Intergenic Spacer Analysis (ARISA) and Denaturing Gradient Gel Electrophoresis (DGGE). ARISA fingerprinting showed that rhizobacterial genetic structure was extremely different from bare soil bacterial communities while rhizobacterial communities clustered strictly together according to the plant species. Sequencing of DGGE bands showed that rhizobacterial communities were mainly composed of Acidobacteria and Proteobacteria whereas bare soil was colonized by Acidobacteria and Clostridia. UniFrac significance calculated on DGGE results confirmed the rhizosphere effect exerted by the 12 species and showed different bacterial communities (P < 0.05) associated with all the plant species. These results pointed out that specific rhizobacterial communities were selected by pioneer plants of different species in a high mountain ecosystem characterized by oligotrophic and harsh environmental conditions, during an early primary succession. PMID- 25110632 TI - Immunogenicity of a monovalent 2009 influenza A (H1N1) vaccine in infants: randomized, observer-masked, single-center clinical study. AB - ABSTRACT: The aim of this study is to further investigate the immune response of the inactivated split-virion vaccine for infants. We tested the immunogenicity and safety of the inactivated split-virion vaccine in infants, aged 6-35 months, for a randomized, observer-masked, age-stratified clinical study. We randomly divided subjects into three groups: 7.5 MUg, 15 MUg of hemagglutinin antigen dosage groups and seasonal influenza vaccine for children dosage group in a 2 dose regimen. A serologic analysis was performed at baseline and on day 21 and 42. 312 infants received a single dose injection of vaccine and 265 (84.94%) infants received two doses injection of vaccine. Adverse reactions were mostly mild or moderate. Among the subjects who received 7.5 MUg and 15 MUg of vaccine for a single dose injection, the rate of hemagglutinin inhibition titer of 1:40 or greater were 52.48% (95% confidence interval (CI) 42.83 ~ 61.95) and 61.11% (95% CI 50.78 ~ 70.53), respectively. Among the subjects receiving 7.5 MUg and 15 MUg of vaccine for two doses injection, the rate of hemagglutinin inhibition (HI) titer of 1:40 or greater were 90.10% (95% CI 82.73 ~ 94.53) and 94.44% (95% CI 87.64 ~ 97.60), respectively. These data suggests that 15 MUg or 7.5 MUg dose of hemagglutinin antigen of the inactivated split-virion vaccine was safe and two doses of injection could induce a sufficient protective immune response in infants. TRIAL REGISTRATION: CLINICAL TRIALS REGISTRATION: NCT01494740. PMID- 25110633 TI - Shigella: A Highly Virulent and Elusive Pathogen. AB - Despite a significant decrease in Shigella-related mortality, shigellosis continues to carry a significant burden of disease worldwide, particularly in Asia and Africa. Shigella is a highly virulent pathogen comprised of four major species with numerous subtypes. Shigella dysenteriae and Shigella flexneri infections are predominant in resource-limited settings. Clinical presentations range from mild watery diarrhea to severe dysentery with systemic complications such as electrolyte imbalance, seizures and hemolytic uremic syndrome. S. dysenteriae subtype 1, the producer of Shiga toxin, causes the most severe illness and highest mortality. Susceptible strains of Shigella may be effectively treated with inexpensive oral antibiotics such as ampicillin or trimethoprim sulfamethoxazole. Unfortunately, multidrug resistant strains have emerged that have rendered most antibiotics, including fluoroquinolones and extended-spectrum cephalosporins, ineffective. Management and prevention of shigellosis represents a major public health challenge. The development of an effective vaccine is urgently needed to decrease its global impact. PMID- 25110634 TI - Weight Loss Programs May Have Beneficial or Adverse Effects on Fat Mass and Insulin Sensitivity in Overweight and Obese Black Women. AB - OBJECTIVE: Weight loss interventions have produced little change in insulin sensitivity in black women, but mean data may obscure metabolic benefit to some and adverse effects for others. Accordingly, we analyzed insulin sensitivity relative to fat mass change following a weight loss program. DESIGN AND METHODS: Fifty-four black women (BMI range 25.9 to 54.7 kg/m2) completed the 6-month program that included nutrition information and worksite exercise facilities. Fat mass was measured by dual-energy X-ray absorptiometry, and insulin sensitivity index (SI) was calculated from an insulin-modified intravenous glucose tolerance test using the minimal model. RESULTS: Baseline SI (range 0.74 to 7.58 l/mU-1*min 1) was inversely associated with fat mass (r = -0.516, p < 0.001), independent of age. On average, subjects lost fat mass (baseline 40.8 +/- 12.4 to 39.4 +/- 12.6 kg [mean +/- SD], P < 0.01), but 17 women (32 %) actually gained fat mass. SI for the group was unchanged (baseline 3.3 +/- 1.7 to 3.2 +/- 1.6, P = 0.67). However, the tertile with greatest fat mass loss (-3.6 kg, range -10.7 to -1.7 kg) improved insulin sensitivity (SI +0.3 +/- 1.2), whereas the tertile with net fat mass gain (+0.9 kg, range -0.1 to +3.8 kg) had reduced insulin sensitivity (SI 0.7 +/- 1.3) from baseline values (P < 0.05 by ANOVA). CONCLUSIONS: Black women in a weight loss program who lose fat mass may have improved insulin sensitivity, but fat mass gain with diminished sensitivity is common. Additional support for participants who fail to achieve fat mass loss early in an intervention may be required for success. PMID- 25110635 TI - Multidrug-resistant tuberculosis treatment with linezolid-containing regimen. AB - The following is a case of multidrug-resistant pulmonary tuberculosis (MDR-TB) that was treated successfully with a linezolid-containing regimen. It was found that linezolid is an efficient medicine for MDR-TB treatment with an acceptable side effect profile. Treatment was maintained for 18 months, and closely monitoring toxicities did not reveal evidence of any neurologic adverse effects. However, despite our expectation, thrombocytopenia was seen after 2 years follow up. PMID- 25110636 TI - Violent crime, suicide, and premature mortality in patients with schizophrenia and related disorders: a 38-year total population study in Sweden. AB - BACKGROUND: People with schizophrenia and related disorders are at an increased risk of adverse outcomes, including conviction of a violent offence, suicide, and premature mortality. However, the rates of, and risk factors for, these outcomes need clarification as a basis for population-based and targeted interventions. We aimed to determine rates and risk factors for these outcomes, and investigate to what extent they are shared across outcomes and are specific to schizophrenia and related disorders. METHODS: We undertook a total population cohort study in Sweden of 24 297 patients with schizophrenia and related disorders between January, 1972 and December, 2009. Patients were matched by age and sex to people from the general population (n=485 940) and also to unaffected sibling controls (n=26 357). First, we investigated rates of conviction of a violent offence, suicide, and premature mortality, with follow-up until conviction of a violent offence, emigration, death, or end of follow-up (Dec 31, 2009), whichever occurred first. Second, we analysed associations between these adverse outcomes and sociodemographic, individual, familial, and distal risk factors, for men and women separately, with Cox proportional hazards models. Finally, we assessed time trends in adverse outcomes between 1972 and 2009, for which we compared patients with unaffected siblings, and analysed associations with changes in the number of nights spent in inpatient beds in psychiatric facilities nationwide. FINDINGS: Within 5 years of their initial diagnosis, 13.9% of men and 4.7% of women with schizophrenia and related disorders had a major adverse outcome (10.7% of men and 2.7% of women were convicted of a violent offence, and 3.3% of men and 2.0% of women died prematurely of any cause). During the study, the adjusted odds ratio of any adverse outcomes for patients compared with general population controls was 7.5 (95% CI 7.2-7.9) in men and 11.1 (10.2-12.1) in women. Three risk factors that were present before diagnosis were predictive of any adverse outcome: drug use disorders, criminality, and self-harm, which were also risk factors for these outcomes in unaffected siblings and in the general population. Over the period 1973-2009, the odds of these outcomes increased in patients with schizophrenia and related disorders compared with unaffected siblings. INTERPRETATION: Schizophrenia and related disorders are associated with substantially increased rates of violent crime, suicide, and premature mortality. Risk factors for these three outcomes included both those specific to individuals with schizophrenia and related disorders, and those shared with the general population. Therefore, a combination of population-based and targeted strategies might be necessary to reduce the substantial rates of adverse outcomes in patients with schizophrenia and related disorders. PMID- 25110637 TI - In vitro cytotoxicity of four calcium silicate-based endodontic cements on human monocytes, a colorimetric MTT assay. AB - OBJECTIVES: This study was performed to evaluate the cytotoxicity of four calcium silicate-based endodontic cements at different storage times after mixing. MATERIALS AND METHODS: Capillary tubes were filled with Biodentine (Septodont), Calcium Enriched Mixture (CEM cement, BioniqueDent), Tech Biosealer Endo (Tech Biosealer) and ProRoot MTA (Dentsply Tulsa Dental). Empty tubes and tubes containing Dycal were used as negative and positive control groups respectively. Filled capillary tubes were kept in 0.2 mL microtubes and incubated at 37C. Each material was divided into 3 groups for testing at intervals of 24 hr, 7 day and 28 day after mixing. Human monocytes were isolated from peripheral blood mononuclear cells and cocultered with 24 hr, 7 day and 28 day samples of different materials for 24 and 48 hr. Cell viability was evaluated using an MTT assay. RESULTS: In all groups, the viability of monocytes significantly improved with increasing storage time regardless of the incubation time (p < 0.001). After 24 hr of incubation, there was no significant difference between the materials regarding monocyte viability. However, at 48 hr of incubation, ProRoot MTA and Biodentine were less cytotoxic than CEM cement and Biosealer (p < 0.01). CONCLUSIONS: Biodentine and ProRoot MTA had similar biocompatibility. Mixing ProRoot MTA with PBS in place of distilled water had no effect on its biocompatibility. Biosealer and CEM cement after 48 hr of incubation were significantly more cytotoxic to on monocyte cells compared to ProRoot MTA and Biodentine. PMID- 25110638 TI - Temperature changes under demineralized dentin during polymerization of three resin-based restorative materials using QTH and LED units. AB - OBJECTIVES: Light-curing of resin-based materials (RBMs) increases the pulp chamber temperature, with detrimental effects on the vital pulp. This in vitro study compared the temperature rise under demineralized human tooth dentin during light-curing and the degrees of conversion (DCs) of three different RBMs using quartz tungsten halogen (QTH) and light-emitting diode (LED) units (LCUs). MATERIALS AND METHODS: Demineralized and non-demineralized dentin disks were prepared from 120 extracted human mandibular molars. The temperature rise under the dentin disks (n = 12) during the light-curing of three RBMs, i.e. an Ormocer based composite resin (Ceram. X, Dentsply DeTrey), a low-shrinkage silorane-based composite (Filtek P90, 3M ESPE), and a giomer (Beautifil II, Shofu GmbH), was measured with a K-type thermocouple wire. The DCs of the materials were investigated using Fourier transform infrared spectroscopy. RESULTS: The temperature rise under the demineralized dentin disks was higher than that under the non-demineralized dentin disks during the polymerization of all restorative materials (p < 0.05). Filtek P90 induced higher temperature rise during polymerization than Ceram.X and Beautifil II under demineralized dentin (p < 0.05). The temperature rise under demineralized dentin during Filtek P90 polymerization exceeded the threshold value (5.5C), with no significant differences between the DCs of the test materials (p > 0.05). CONCLUSIONS: Although there were no significant differences in the DCs, the temperature rise under demineralized dentin disks for the silorane-based composite was higher than that for dimethacrylate-based restorative materials, particularly with QTH LCU. PMID- 25110639 TI - How to design in situ studies: an evaluation of experimental protocols. AB - OBJECTIVES: Designing in situ models for caries research is a demanding procedure, as both clinical and laboratory parameters need to be incorporated in a single study. This study aimed to construct an informative guideline for planning in situ models relevant to preexisting caries studies. MATERIALS AND METHODS: An electronic literature search of the PubMed database was performed. A total 191 of full articles written in English were included and data were extracted from materials and methods. Multiple variables were analyzed in relation to the publication types, participant characteristics, specimen and appliance factors, and other conditions. Frequencies and percentages were displayed to summarize the data and the Pearson's chi-square test was used to assess a statistical significance (p < 0.05). RESULTS: There were many parameters commonly included in the majority of in situ models such as inclusion criteria, sample sizes, sample allocation methods, tooth types, intraoral appliance types, sterilization methods, study periods, outcome measures, experimental interventions, etc. Interrelationships existed between the main research topics and some parameters (outcome measures and sample allocation methods) among the evaluated articles. CONCLUSIONS: It will be possible to establish standardized in situ protocols according to the research topics. Furthermore, data collaboration from comparable studies would be enhanced by homogeneous study designs. PMID- 25110640 TI - Effect of 38% carbamide peroxide on the microleakage of silorane-based versus methacrylate-based composite restorations. AB - OBJECTIVES: This study aimed to assess the effect of 38% carbamide peroxide on the microleakage of class V cavities restored with either a silorane-based composite or two methacrylate-based composites. MATERIALS AND METHODS: A total of 96 class V cavities were prepared on the buccal surface of extracted human teeth with both enamel and dentin margins and were randomly assigned into three groups of Filtek P90 (3M-ESPE) + P90 system adhesive (3M-ESPE)(group A), Filtek Z250 (3M ESPE) + Adper Prompt L-Pop (3M-ESPE)(group B) and Filtek Z350XT (3M-ESPE) + Adper Prompt L-Pop (group C). Half of the teeth were randomly underwent bleaching (38% carbamide peroxide, Day White, Discus Dental, applying for 15 min, twice a day for 14 day) while the remaining half (control) were not bleached. Dye penetration was measured following immersion in basic fuchsine. Data were statistically analyzed using Kruskal-Wallis and Mann-Whitney U tests at a level of 0.05. RESULTS: No significant differences were found between composites in the control groups in enamel (p = 0.171) or dentin (p = 0.094) margins. After bleaching, microleakage of Z250 (in enamel [p = 0.867] or dentin [p = 0.590] margins) and Z350 (in enamel [p = 0.445] or dentin [p = 0.591] margins) did not change significantly, but the microleakage of P90 significantly increased in both enamel (p = 0.042) and dentin (p = 0.002) margins. CONCLUSIONS: No significant differences were noted between the bleached and control subgroups of two methacrylate-based composites in enamel or dentin margins. Microleakage of silorane-based composite significantly increased after bleaching. PMID- 25110641 TI - Enamel pretreatment with Er:YAG laser: effects on the microleakage of fissure sealant in fluorosed teeth. AB - OBJECTIVES: The purpose of this in vitro study was to evaluate the microleakage and penetration of fissure sealant in permanent molar teeth with fluorosis after pretreatment of the occlusal surface. MATERIALS AND METHODS: A total of 120 third molars with mild dental fluorosis were randomly divided into 6 groups (n = 20). The tooth surfaces were sealed with an unfilled resin fissure sealant (FS) material. The experimental groups included: 1) phosphoric acid etching (AE) + FS (control); 2) AE + One-Step Plus (OS, Bisco) + FS; 3) bur + AE + FS; 4) bur + AE + OS + FS; 5) Er:YAG laser + AE + FS; and 6) Er:YAG laser + AE + OS + FS. After thermocycling, the teeth were immersed in 0.5% fuchsin and sectioned. Proportions of mircoleakage (PM) and unfilled area (PUA) were measured by digital microscope. RESULTS: Overall, there were significant differences among all groups in the PM (p = 0.00). Group 3 showed the greatest PM, and was significantly different from groups 2 to 6 (p < 0.05). Group 6 showed the lowest PM. Pretreatment with Er:YAG with or without adhesive led to less PM than bur pretreatment. There were no significant differences among groups in PUA. CONCLUSIONS: Conventional acid etching provided a similar degree of occlusal seal in teeth with fluorosis compared to those pretreated with a bur or Er:YAG laser. Pretreatment of pits and fissures with Er:YAG in teeth with fluorosis may be an alternative method before fissure sealant application. PMID- 25110642 TI - The effects of bone morphogenetic protein-2 and enamel matrix derivative on the bioactivity of mineral trioxide aggregate in MC3T3-E1cells. AB - OBJECTIVES: The effects of bone morphogenetic protein-2 (BMP-2) and enamel matrix derivative (EMD) respectively with mineral trioxide aggregate (MTA) on hard tissue regeneration have been investigated in previous studies. This study aimed to compare the osteogenic effects of MTA/BMP-2 and MTA/EMD treatment in MC3T3-E1 cells. MATERIALS AND METHODS: MC3T3-E1 cells were treated with MTA (ProRoot, Dentsply), BMP-2 (R&D Systems), EMD (Emdogain, Straumann) separately and MTA/BMP 2 or MTA/EMD combination. Mineralization was evaluated by staining the calcium deposits with alkaline phosphatase (ALP, Sigma-Aldrich) and Alizarin red (Sigma Aldrich). The effects on the osteoblast differentiation were evaluated by the expressions of osteogenic markers, including ALP, bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN) and osteonectin (OSN), as determined by reverse-transcription polymerase chain reaction analysis (RT-PCR, AccuPower PCR, Bioneer). RESULTS: Mineralization increased in the BMP-2 and MTA/BMP-2 groups and increased to a lesser extent in the MTA/EMD group but appeared to decrease in the MTA-only group based on Alizarin red staining. ALP expression largely decreased in the EMD and MTA/EMD groups based on ALP staining. In the MTA/BMP-2 group, mRNA expression of OPN on day 3 and BSP and OCN on day 7 significantly increased. In the MTA/EMD group, OSN and OCN gene expression significantly increased on day 7, whereas ALP expression decreased on days 3 and 7 (p < 0.05). CONCLUSIONS: These results suggest the MTA/BMP-2 combination promoted more rapid differentiation in MC3T3-E1 cells than did MTA/EMD during the early mineralization period. PMID- 25110643 TI - Comparative efficacy of photo-activated disinfection and calcium hydroxide for disinfection of remaining carious dentin in deep cavities: a clinical study. AB - OBJECTIVES: To comparatively evaluate the efficacy of photo-activated disinfection (PAD), calcium hydroxide (CH) and their combination on the treatment outcome of indirect pulp treatment (IPT). MATERIALS AND METHODS: Institutional ethical clearance and informed consent of the patients were taken. The study was also registered with clinical registry of India. Sixty permanent molars exhibiting deep occlusal carious lesion in patients with the age range of 18 - 22 yr were included. Clinical and radiographic evaluation and set inclusion and exclusion criteria's were followed. Gross caries excavation was accomplished. In group I (n = 20) PAD was applied for sixty seconds. In group II (n = 20), CH was applied to the remaining carious dentin, while in group III (n = 20), PAD application was followed by CH placement. The teeth were permanently restored. They were clinically and radiographically followed-up at 45 day, 6 mon and 12 mon. Relative density of the remaining affected dentin was measured by 'Radiovisiography (RVG) densitometric' analysis. RESULTS: Successful outcome with an increase in radiographic grey values were observed in all three groups. However, on inter-group comparison, this change was not significant (p > 0.05). CONCLUSIONS: PAD and CH both have equal disinfection efficacy in the treatment of deep carious dentin. PAD alone is as effective for treatment of deep carious lesion as calcium hydroxide and hence can be used as an alternative to CH. They can be used independently in IPT, since combining both does not offer any additional therapeutic benefits. PMID- 25110644 TI - Comparative analysis of physicochemical properties of root perforation sealer materials. AB - OBJECTIVES: This study evaluated the solubility, dimensional alteration, pH, electrical conductivity, and radiopacity of root perforation sealer materials. MATERIALS AND METHODS: For the pH test, the samples were immersed in distilled water for different periods of time. Then, the samples were retained in plastic recipients, and the electrical conductivity of the solution was measured. The solubility, dimensional alteration, and radiopacity properties were evaluated according to Specification No. 57 of the American National Standards Institute/American Dental Association (ANSI/ADA). Statistical analyses were carried out using analysis of variance (ANOVA) and Tukey's test at a significance level of 5%. When the sample distribution was not normal, a nonparametric ANOVA was performed with a Kruskal-Wallis test (alpha = 0.05). RESULTS: The results showed that white structural Portland cement (PC) had the highest solubility, while mineral trioxide aggregate (MTA)-based cements, ProRoot MTA (Dentsply-Tulsa Dental) and MTA BIO (Angelus Ind. Prod.), had the lowest values. MTA BIO showed the lowest dimensional alteration values and white PC presented the highest values. No differences among the tested materials were observed in the the pH and electrical conductivity analyses. Only the MTA-based cements met the ANSI/ADA recommendations regarding radiopacity, overcoming the three steps of the aluminum step wedge. CONCLUSIONS: On the basis of these results, we concluded that the values of solubility and dimensional alteration of the materials were in accordance with the ANSI/ADA specifications. PCs did not fulfill the ANSI/ADA requirements regarding radiopacity. No differences were observed among the materials with respect to the pH and electrical conductivity analyses. PMID- 25110645 TI - Prevalence of referral reasons and clinical symptoms for endodontic referrals. AB - OBJECTIVES: To investigate the prevalence of different primary reasons for endodontic referrals and the clinical symptoms of the referred cases. MATERIALS AND METHODS: Clinical data of total endodontic treatment cases (1,014 teeth) including endodontic referral cases (224 teeth) between January 1, 2010 and December 31, 2012, at Kangdong Sacred Heart Hospital, were investigated retrospectively. The one major reason for referral, the clinical symptoms, and the resulting treatment procedures of referral cases were recorded. The percentages of clinical symptoms of the endodontic referral cases and the total endodontic treatment cases were compared by chi(2) test for each symptom. RESULTS: Persistent pain was the most frequent reason for endodontic referral (29.5%), followed by presence of gingival swelling and sinus tract (24.1%), and apical radiolucency (12.9%). Referrals in cases involving endodontic difficulties such as canal calcification, broken instruments, post, perforation, and resorption were less than 5.0%, respectively. The percentages of four major clinical symptoms of pain, apical radiolucency, previous endodontic treatment, and gingival swelling and sinus tract were significantly higher in the endodontic referral cases than those in the total endodontic cases (p = 0.001). Among the included referral cases, 72.8% were treated with nonsurgical endodontic treatment only. Teeth other than the referred teeth were diagnosed as the origin of the problem in 5.8% of the referrals. CONCLUSIONS: The high prevalence of pain, apical radiolucency, previous treatment, and gingival swelling and sinus tract in endodontic referral cases suggest that these symptoms may be what general practitioners consider to be difficult and refer to endodontists. PMID- 25110646 TI - Mental nerve paresthesia secondary to initiation of endodontic therapy: a case report. AB - Whenever endodontic therapy is performed on mandibular posterior teeth, damage to the inferior alveolar nerve or any of its branches is possible. Acute periapical infection in mandibular posterior teeth may also sometimes disturb the normal functioning of the inferior alveolar nerve. The most common clinical manifestation of these insults is the paresthesia of the inferior alveolar nerve or mental nerve paresthesia. Paresthesia usually manifests as burning, prickling, tingling, numbness, itching or any deviation from normal sensation. Altered sensation and pain in the involved areas may interfere with speaking, eating, drinking, shaving, tooth brushing and other events of social interaction which will have a disturbing impact on the patient. Paresthesia can be short term, long term or even permanent. The duration of the paresthesia depends upon the extent of the nerve damage or persistence of the etiology. Permanent paresthesia is the result of nerve trunk laceration or actual total nerve damage. Paresthesia must be treated as soon as diagnosed to have better treatment outcomes. The present paper describes a case of mental nerve paresthesia arising after the start of the endodontic therapy in left mandibular first molar which was managed successfully by conservative treatment. PMID- 25110647 TI - Esthetic rehabilitation of single anterior edentulous space using fiber reinforced composite. AB - A fiber-reinforced composite (FRC) fixed prosthesis is an innovative alternative to a traditional metal restoration, as it is a conservative treatment method. This case report demonstrates a detailed procedure for restoring a missing anterior tooth with an FRC. A 44-year-old woman visited our department with an avulsed tooth that had fallen out on the previous day and was completely dry. This tooth was replanted, but it failed after one year. A semi-direct technique was used to fabricate a FRC fixed partial prosthesis for its replacement. The FRC framework and the pontic were fabricated using a duplicated cast model and nanofilled composite resin. Later on, interproximal contact, tooth shape, and shade were adjusted at chairside. This technique not only enables the clinician to replace a missing tooth immediately after extraction for minimizing esthetic problems, but it also decreases both tooth reduction and cost. PMID- 25110648 TI - An esthetic appliance for the management of crown-root fracture: a case report. AB - Orthodontic extrusion is usually performed by means of a fixed orthodontic appliance that utilizes arch wire attached to adjacent teeth and transfers the desired force by elastic from the wire to the root. However, clinicians often encounter cases where the bonding required for tooth traction is not possible because the adjacent teeth have been restored with ceramic or veneer. The purpose of this case report is to describe a modified orthodontic extrusion appliance that is useful when conventional orthodontic treatment is not possible. The modified appliance was fabricated using an artificial tooth, clear plastic sheeting, and a braided fiber-reinforced composite strip that covered adjacent teeth without bonding. It satisfied the esthetic and functional needs of the patient and established the optimal biologic width. PMID- 25110650 TI - Statistical notes for clinical researchers: Nonparametric statistical methods: 1. Nonparametric methods for comparing two groups. PMID- 25110649 TI - The use of platelet rich plasma in the treatment of immature tooth with periapical lesion: a case report. AB - This study describes the treatment of an immature permanent tooth with periapical lesion which was treated with regenerative approach using platelet rich plasma (PRP). The root canal of immature human permanent tooth with periapical lesion was gently debrided of necrotic tissue and disinfected with 2.5% NaOCl, and then medicated with triple antibiotic paste comprised of ciprofloxacin, metronidazole, and tetracycline. When the tooth was asymptomatic, PRP and mineral trioxide aggregate (MTA) were placed into the root canal. Six months after PRP treatment, radiographical examination revealed resolution of the radiolucency and progressive thickening of the root wall and apical closure. Our findings suggest that PRP can be used for the treatment of immature permanent teeth with periapical lesion, as part of a regenerative endodontic treatment procedure. PMID- 25110651 TI - Rotational stability of endodontic motors. PMID- 25110652 TI - Identification of Differentially Expressed Gene after Femoral Fracture via Microarray Profiling. AB - We aimed to investigate differentially expressed genes (DEGs) in different stages after femoral fracture based on rat models, providing the basis for the treatment of sport-related fractures. Gene expression data GSE3298 was downloaded from Gene Expression Omnibus (GEO), including 16 chips. All femoral fracture samples were classified into earlier fracture stage and later fracture stage. Total 87 DEGs simultaneously occurred in two stages, of which 4 genes showed opposite expression tendency. Out of the 4 genes, Rest and Cst8 were hub nodes in protein protein interaction (PPI) network. The GO (Gene Ontology) function enrichment analysis verified that nutrition supply related genes were enriched in the earlier stage and neuron growth related genes were enriched in the later stage. Calcium signaling pathway was the most significant pathway in earlier stage; in later stage, DEGs were enriched into 2 neurodevelopment-related pathways. Analysis of Pearson's correlation coefficient showed that a total of 3,300 genes were significantly associated with fracture time, none of which was overlapped with identified DEGs. This study suggested that Rest and Cst8 might act as potential indicators for fracture healing. Calcium signaling pathway and neurodevelopment-related pathways might be deeply involved in bone healing after femoral fracture. PMID- 25110653 TI - Stereotactic body radiotherapy for small lung tumors in the University of Tokyo Hospital. AB - Our work on stereotactic body radiation therapy (SBRT) for primary and metastatic lung tumors will be described. The eligibility criteria for SBRT, our previous SBRT method, the definition of target volume, heterogeneity correction, the position adjustment using four-dimensional cone-beam computed tomography (4D CBCT) immediately before SBRT, volumetric modulated arc therapy (VMAT) method for SBRT, verifying of tumor position within internal target volume (ITV) using in treatment 4D-CBCT during VMAT-SBRT, shortening of treatment time using flattening filter-free (FFF) techniques, delivery of 4D dose calculation for lung-VMAT patients using in-treatment CBCT and LINAC log data with agility multileaf collimator, and SBRT method for centrally located lung tumors in our institution will be shown. In our institution, these efforts have been made with the goal of raising the local control rate and decreasing adverse effects after SBRT. PMID- 25110654 TI - Evaluation of cocktails with recombinant proteins of Mycobacterium bovis for a specific diagnosis of bovine tuberculosis. AB - The Delayed type hypersensitivity skin test (DTH) and interferon-gamma assay are used for the diagnosis of bovine tuberculosis (TBB). The specificity of these diagnoses, however, is compromised because both are based on the response against purified protein derivative of Mycobacterium bovis (PPD-B). In this study, we assessed the potential of two cocktails containing M. bovis recombinant proteins: cocktail 1 (C1): ESAT-6, CFP-10 and MPB83 and cocktail 2 (C2): ESAT-6, CFP-10, MPB83, HspX, TB10.3, and MPB70. C1, C2, and PPD-B showed similar response by DTH in M. bovis-sensitized guinea pigs. Importantly, C1 induced a lower response than PPD-B in M. avium-sensitized guinea pigs. In cattle, C1 displayed better performance than PPD-B and C2; indeed, C1 showed the least detection of animals either vaccinated or Map-infected. To optimize the composition of the cocktails, we obtained protein fractions from PPD-B and tested their immunogenicity in experimentally M. bovis-infected cattle. In one highly reactive fraction, seven proteins were identified. The inclusion of FixB in C1 enhanced the recognition of M. bovis-infected cattle without compromising specificity. Our data provide a promising basis for the future development of a cocktail for TBB detection without interference by the presence of sensitized or infected animals with other mycobacteria. PMID- 25110655 TI - Development and characterization of novel porous 3D alginate-cockle shell powder nanobiocomposite bone scaffold. AB - A novel porous three-dimensional bone scaffold was developed using a natural polymer (alginate/Alg) in combination with a naturally obtained biomineral (nano cockle shell powder/nCP) through lyophilization techniques. The scaffold was developed in varying composition mixture of Alg-nCP and characterized using various evaluation techniques as well as preliminary in vitro studies on MG63 human osteoblast cells. Morphological observations using SEM revealed variations in structures with the use of different Alg-nCP composition ratios. All the developed scaffolds showed a porous structure with pore sizes ideal for facilitating new bone growth; however, not all combination mixtures showed subsequent favorable characteristics to be used for biological applications. Scaffolds produced using the combination mixture of 40% Alg and 60% nCP produced significantly promising results in terms of mechanical strength, degradation rate, and increased cell proliferation rates making it potentially the optimum composition mixture of Alg-nCP with future application prospects. PMID- 25110656 TI - Assessment of food processing and pharmaceutical industrial wastes as potential biosorbents: a review. AB - There is a growing need for the use of low-cost and ecofriendly adsorbents in water/wastewater treatment applications. Conventional adsorbents as well as biosorbents from different natural and agricultural sources have been extensively studied and reviewed. However, there is a lack of reviews on biosorption utilizing industrial wastes, particularly those of food processing and pharmaceuticals. The current review evaluates the potential of these wastes as biosorbents for the removal of some hazardous contaminants. Sources and applications of these biosorbents are presented, while factors affecting biosorption are discussed. Equilibrium, kinetics, and mechanisms of biosorption are also reviewed. In spite of the wide spread application of these biosorbents in the treatment of heavy metals and dyes, more research is required on other classes of pollutants. In addition, further work should be dedicated to studying scaling up of the process and its economic feasibility. More attention should also be given to enhancing mechanical strength, stability, life time, and reproducibility of the biosorbent. Environmental concerns regarding disposal of consumed biosorbents should be addressed by offering feasible biosorbent regeneration or pollutant immobilization options. PMID- 25110657 TI - The effects of apigenin on the expression of Fas/FasL apoptotic pathway in warm liver ischemia-reperfusion injury in rats. AB - BACKGROUND: The aim of this experimental study was to investigate the role of apigenin in liver apoptosis, in an experimental model of hepatic ischemia reperfusion in rats. MATERIALS AND METHODS: Forty-eight Wistar rats (apigenin and control groups), 14 to 16 weeks old and weighing 220 to 350 g, were used. They were all subjected to hepatic ischemia by occlusion of the hepatic artery and portal vein for 45 minutes and reperfusion was followed for 60, 120, and 240 minutes. Apigenin was administrated intraperitoneally. Liver tissues were used for the detection of apoptosis by TUNEL assay and caspase 3 antibodies. Expression analysis of Fas/FasL genes was evaluated by real time PCR. RESULTS: The expression analysis of Fas and FasL genes was increasing during reperfusion (significantly in the group of 240 minutes of reperfusion). It was in the same group that apigenin decreased Fas receptor levels and inhibited apoptosis as confirmed by TUNEL assay and caspase 3 antibodies. CONCLUSIONS: The effects of apigenin in the Fas/FasL mediated pathway of apoptosis, in the hepatic ischemia reperfusion, seem to have a protective result on the hepatic cell. PMID- 25110658 TI - The role of microclot formation in an acute subarachnoid hemorrhage model in the rabbit. AB - BACKGROUND: Microvascular dysfunction and microthrombi formation are believed to contribute to development of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE: This study aimed to determine (i) extent of microthrombus formation and neuronal apoptosis in the brain parenchyma using a blood shunt SAH model in rabbits; (ii) correlation of structural changes in microvessels with EBI characteristics. METHODS: Acute SAH was induced using a rabbit shunt cisterna magna model. Extent of microthrombosis was detected 24 h post-SAH (n = 8) by fibrinogen immunostaining, compared to controls (n = 4). We assessed apoptosis by terminal deoxynucleotidyl transferase nick end labeling (TUNEL) in cortex and hippocampus. RESULTS: Our results showed significantly more TUNEL-positive cells (SAH: 115 +/- 13; controls: 58 +/- 10; P = 0.016) and fibrinogen-positive microthromboemboli (SAH: 9 +/- 2; controls: 2 +/- 1; P = 0.03) in the hippocampus after aneurysmal SAH. CONCLUSIONS: We found clear evidence of early microclot formation in a rabbit model of acute SAH. The extent of microthrombosis did not correlate with early apoptosis or CPP depletion after SAH; however, the total number of TUNEL positive cells in the cortex and the hippocampus significantly correlated with mean CPP reduction during the phase of maximum depletion after SAH induction. Both microthrombosis and neuronal apoptosis may contribute to EBI and subsequent DCI. PMID- 25110659 TI - Risk factors for mortality in patients with septic acute kidney injury in intensive care units in Beijing, China: a multicenter prospective observational study. AB - OBJECTIVE: To discover risk factors for mortality of patients with septic AKI in ICU via a multicenter study. BACKGROUND: Septic AKI is a serious threat to patients in ICU, but there are a few clinical studies focusing on this. METHODS: This was a prospective, observational, and multicenter study conducted in 30 ICUs of 28 major hospitals in Beijing. 3,107 patients were admitted consecutively, among which 361 patients were with septic AKI. Patient clinical data were recorded daily for 10 days after admission. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to define and stage AKI. Of the involved patients, 201 survived and 160 died. RESULTS: The rate of septic AKI was 11.6%. Twenty-one risk factors were found, and six independent risk factors were identified: age, APACHE II score, duration of mechanical ventilation, duration of MAP <65 mmHg, time until RRT started, and progressive KIDGO stage. Admission KDIGO stages were not associated with mortality, while worst KDIGO stages were. Only progressive KIDGO stage was an independent risk factor. CONCLUSIONS: Six independent risk factors for mortality for septic AKI were identified. Progressive KIDGO stage is better than admission or the worst KIDGO for prediction of mortality. This trial is registered with ChiCTR-ONC-11001875. PMID- 25110660 TI - Beta-thalassaemia intermedia: evaluation of endocrine and bone complications. AB - OBJECTIVE: Data about endocrine and bone disease in nontransfusion-dependent thalassaemia (NTDT) is scanty. The aim of our study was to evaluate these complications in beta-TI adult patients. METHODS: We studied retrospectively 70 beta-TI patients with mean followup of 20 years. Data recorded included age, gender, haemoglobin and ferritin levels, biochemical and endocrine tests, liver iron concentration (LIC) from T2*, transfusion regimen, iron chelation, hydroxyurea, splenectomy, and bone mineralization by dual X-ray absorptiometry. RESULTS: Thirty-seven (53%) males and 33 (47%) females were studied, with mean age 41 +/- 12 years, mean haemoglobin 9.2 +/- 1.5 g/dL, median ferritin 537 (range 14-4893), and mean LIC 7.6 +/- 6.4 mg Fe/g dw. Thirty-three patients (47%) had been transfused, occasionally (24/33; 73%) or regularly (9/33; 27%); 37/70 (53%) had never been transfused; 34/70 patients had been splenectomized (49%); 39 (56%) were on chelation therapy; and 11 (16%) were on hydroxyurea. Endocrinopathies were found in 15 patients (21%): 10 hypothyroidism, 3 hypogonadism, 2 impaired glucose tolerance (IGT), and one diabetes. Bone disease was observed in 53/70 (76%) patients, osteoporosis in 26/53 (49%), and osteopenia in 27/53 (51%). DISCUSSION AND CONCLUSIONS: Bone disease was found in most patients in our study, while endocrinopathies were highly uncommon, especially hypogonadism. We speculate that low iron burden may protect against endocrinopathy development. PMID- 25110661 TI - Mechatronic feasibility of minimally invasive, atraumatic cochleostomy. AB - Robotic assistance in the context of lateral skull base surgery, particularly during cochlear implantation procedures, has been the subject of considerable research over the last decade. The use of robotics during these procedures has the potential to provide significant benefits to the patient by reducing invasiveness when gaining access to the cochlea, as well as reducing intracochlear trauma when performing a cochleostomy. Presented herein is preliminary work on the combination of two robotic systems for reducing invasiveness and trauma in cochlear implantation procedures. A robotic system for minimally invasive inner ear access was combined with a smart drilling tool for robust and safe cochleostomy; evaluation was completed on a single human cadaver specimen. Access to the middle ear was successfully achieved through the facial recess without damage to surrounding anatomical structures; cochleostomy was completed at the planned position with the endosteum remaining intact after drilling as confirmed by microscope evaluation. PMID- 25110662 TI - A novel COL4A5 mutation identified in a Chinese Han family using exome sequencing. AB - Alport syndrome (AS) is a monogenic disease of the basement membrane (BM), resulting in progressive renal failure due to glomerulonephropathy, variable sensorineural hearing loss, and ocular anomalies. It is caused by mutations in the collagen type IV alpha-3 gene (COL4A3), the collagen type IV alpha-4 gene (COL4A4), and the collagen type IV alpha-5 gene (COL4A5), which encodes type IV collagen alpha3, alpha4, and alpha5 chains, respectively. To explore the disease related gene in a four-generation Chinese Han pedigree of AS, exome sequencing was conducted on the proband, and a novel deletion mutation c.499delC (p.Pro167Glnfs*36) in the COL4A5 gene was identified. This mutation, absent in 1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls, cosegregated with patients in the family. Neither sensorineural hearing loss nor typical COL4A5-related ocular abnormalities (dot-and-fleck retinopathy, anterior lenticonus, and the rare posterior polymorphous corneal dystrophy) were present in patients of this family. The phenotypes of patients in this AS family were characterized by early onset-age and rapidly developing into end-stage renal disease (ESRD). Our discovery broadens the mutation spectrum in the COL4A5 gene associated with AS, which may also shed new light on genetic counseling for AS. PMID- 25110663 TI - The impact of tobacco smoke exposure on wheezing and overweight in 4-6-year-old children. AB - AIM: To investigate the association between maternal smoking during pregnancy, second-hand tobacco smoke (STS) exposure, education level, and preschool children's wheezing and overweight. METHODS: This cohort study used data of the KANC cohort--1,489 4-6-year-old children from Kaunas city, Lithuania. Multivariate logistic regression was employed to study the influence of prenatal and postnatal STS exposure on the prevalence of wheezing and overweight, controlling for potential confounders. RESULTS: Children exposed to maternal smoking during pregnancy had a slightly increased prevalence of wheezing and overweight. Postnatal exposure to STS was associated with a statistically significantly increased risk of wheezing and overweight in children born to mothers with lower education levels (OR 2.12; 95% CI 1.04-4.35 and 3.57; 95% CI 1.76-7.21, accordingly). CONCLUSIONS: The present study findings suggest that both maternal smoking during pregnancy and STS increase the risk of childhood wheezing and overweight, whereas lower maternal education might have a synergetic effect. Targeted interventions must to take this into account and address household smoking. PMID- 25110664 TI - Cloning, expression, purification, and characterization of glutaredoxin from Antarctic sea-ice bacterium Pseudoalteromonas sp. AN178. AB - Glutaredoxins (Grxs) are small ubiquitous redox enzymes that catalyze glutathione dependent reactions to reduce protein disulfide. In this study, a full-length Grx gene (PsGrx) with 270 nucleotides was isolated from Antarctic sea-ice bacterium Pseudoalteromonas sp. AN178. It encoded deduced 89 amino acid residues with the molecular weight 9.8 kDa. Sequence analysis of the amino acid sequence revealed the catalytic motif CPYC. Recombinant PsGrx (rPsGrx) stably expressed in E. coli BL21 was purified to apparent homogeneity by Ni-affinity chromatography. rPsGrx exhibited optimal activity at 30 degrees C and pH 8.0 and showed 25.5% of the activity at 0 degrees C. It retained 65.0% of activity after incubation at 40 degrees C for 20 min and still exhibited 37.0% activity in 1.0 M NaCl. These results indicated that rPsGrx was a typical cold active protein with low thermostability. PMID- 25110665 TI - Emerging microbial concerns in food safety and new control measures. PMID- 25110666 TI - Evaluation of growth patterns and body composition in C57Bl/6J mice using dual energy X-ray absorptiometry. AB - The normal growth pattern of female C57BL/6J mice, from 5 to 30 weeks of age, has been investigated in a longitudinal study. Weight, body surface area (BS), and body mass index (BMI) were evaluated in forty mice. Lean mass and fat mass, bone mineral content (BMC), and bone mineral density (BMD) were monitored by dual energy X-ray absorptiometry (DEXA). Weight and BS increased linearly (16.15 +/- 0.64-27.64 +/- 1.42 g; 51.13 +/- 0.74-79.57 +/- 2.15 cm(2), P < 0.01), more markedly from 5 to 9 weeks of age (P < 0.001). BMD showed a peak at 17 weeks (0.0548 +/- 0.0011 g/cm(2) * m, P < 0.01). Lean mass showed an evident gain at 9 (15.8 +/- 0.8 g, P < 0.001) and 25 weeks (20.5 +/- 0.3 g, P < 0.01), like fat mass from 13 to 17 weeks (2.0 +/- 0.4-3.6 +/- 0.7 g, P < 0.01). BMI and lean mass index (LMI) reached the highest value at 21 weeks (3.57 +/- 0.02-0.284 +/- 0.010 g/cm(2), resp.), like fat mass index (FMI) at 17 weeks (0.057 +/- 0.009 g/cm(2)) (P < 0.01). BMI, weight, and BS showed a moderate positive correlation (0.45 0.85) with lean mass from 5 to 21 weeks. Mixed linear models provided a good prediction for lean mass, fat mass, and BMD. This study may represent a baseline reference for a future comparison of wild-type C57BL/6J mice with models of altered growth. PMID- 25110667 TI - Usefulness of anticoagulant therapy in the prevention of embolic complications in patients with acute infective endocarditis. AB - BACKGROUND: The use of anticoagulant therapy (ACT) in patients with acute infective endocarditis (IE) remains a controversial issue. Our study attempts to estimate the impact of ACT on the occurrence of embolic complications and the usefulness of ACT in the prevention of embolism in IE patients. METHODS: The present authors analyzed 150 patients with left-sided IE. Embolisms including cerebrovascular events (CVE) and the use of ACT were checked at the time of admission and during hospitalization. RESULTS: 57 patients (38.0%) experienced an embolic event. There was no significant difference in the incidence of CVE and in hospital mortality between patients with and without warfarin use at admission, although warfarin-naive patients were significantly more likely to have large (>1 cm) and mobile vegetation. In addition, there was no significant difference in the incidence of postadmission embolism and in-hospital death between patients with and without in-hospital ACT. On multivariate logistic regression analysis, ACT at admission was not significantly associated with a lower risk of embolism in patients with IE. CONCLUSIONS: The role of ACT in the prevention of embolism was limited in IE patients undergoing antibiotic therapy, although it seems to reduce the embolic potential of septic vegetation before treatment. PMID- 25110668 TI - Assessment of the optic disc morphology using spectral-domain optical coherence tomography and scanning laser ophthalmoscopy. AB - OBJECTIVE: To compare the equivalent optic nerve head (OHN) parameters obtained with confocal scanning laser ophthalmoscopy (HRT3) and spectral-domain optical coherence tomography (OCT) in healthy and glaucoma patients. METHODS: One hundred and eighty-two consecutive healthy subjects and 156 patients with open-angle glaucoma were divided into 2 groups according to intraocular pressure and visual field outcomes. All participants underwent imaging of the ONH with the HRT3 and the Cirrus OCT. The ONH parameters and the receiver operating characteristic (ROC) curves were compared between both groups. RESULTS: Mean age did not differ between the normal and glaucoma groups (59.55 +/- 9.7 years and 61.05 +/- 9.4 years, resp.; P = 0.15). Rim area, average cup-to-disc (C/D) ratio, vertical C/D ratio, and cup volume were different between both instruments (P < 0.001). All equivalent ONH parameters, except disc area, were different between both groups (P < 0.001). The best areas under the ROC curve were observed for vertical C/D ratio (0.980 for OCT and 0.942 for HRT3; P = 0.11). Sensitivities at 95% fixed specificities of OCT parameters were higher than those of HRT3. CONCLUSIONS: Equivalent ONH parameters of Cirrus OCT and HRT3 are different and cannot be used interchangeably. ONH parameters measured with OCT yielded a slightly better diagnostic performance. PMID- 25110669 TI - Mycobacterium tuberculosis P-type ATPases: possible targets for drug or vaccine development. AB - Tuberculosis (TB) has been the biggest killer in the human history; currently, Mycobacterium tuberculosis (Mtb) kills nearly 2 million people each year worldwide. The high prevalence of TB obligates the identification of new therapeutic targets and the development of anti-TB vaccines that can control multidrug resistance and latent TB infections. Membrane proteins have recently been suggested as key targets for bacterial viability. Current studies have shown that mycobacteria P-type ATPases may play critical roles in ion homeostasis and in the response of mycobacteria to toxic substances in the intraphagosomal environment. In this review, we bring together the genomic, transcriptomic, and structural aspects of the P-type ATPases that are relevant during active and latent Mtb infections, which can be useful in determining the potential of these ATPases as drug targets and in uncovering their possible roles in the development of new anti-TB attenuated vaccines. PMID- 25110670 TI - Preparation of three-dimensional vascularized MSC cell sheet constructs for tissue regeneration. AB - Engineering three-dimensional (3D) vascularized constructs remains a challenge due to the inability to form rich microvessel networks. In this study we engineered a prevascularized 3D cell sheet construct for tissue regeneration using human bone marrow-derived mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells as cell sources. hMSCs were cultured to form a thick cell sheet, and human umbilical vein endothelial cells (HUVECs) were then seeded on the hMSCs sheet to form networks. The single prevascularized HUVEC/hMSC cell sheet was folded to form a 3D construct by a modified cell sheet engineering technique. In vitro results indicated that the hMSCs cell sheet promoted the HUVECs cell migration to form networks in horizontal and vertical directions. In vivo results showed that many blood vessels grew into the 3D HUVEC/hMSC cell sheet constructs after implanted in the subcutaneous pocket of immunodeficient mice. The density of blood vessels in the prevascularized constructs was higher than that in the nonprevascularized constructs. Immunohistochemistry staining further showed that in vitro preformed human capillaries in the prevascularized constructs anastomosed with the host vasculature to form functional blood vessels. These results suggest the promising potential of this 3D prevascularized construct using hMSCs cell sheet as a platform for wide applications in engineering vascularized tissues. PMID- 25110671 TI - Tick-borne encephalitis virus habitats in North East Germany: reemergence of TBEV in ticks after 15 years of inactivity. AB - The incidence of tick-borne encephalitis has risen in Europe since 1990 and the tick-borne encephalitis virus (TBEV) has been documented to be spreading into regions where it was not previously endemic. In Mecklenburg-West Pomerania, a federal state in Northern Germany, TBEV was not detectable in over 16,000 collected ticks between 1992 and 2004. Until 2004, the last human case of TBE in the region was reported in 1985. Following the occurrence of three autochthonous human cases of TBE after 2004, however, we collected ticks from the areas in which the infections were contracted. To increase the chance of detecting TBEV RNA, some of the ticks were fed on mice. Using nested RT-PCR, we were able to confirm the presence of TBEV in ticks for the first time after 15 years. A phylogenetic analysis revealed a close relationship between the sequences we obtained and a TBEV sequence from Mecklenburg-East Pomerania published in 1992 and pointed to the reemergence of a natural focus of TBEV after years of low activity. Our results imply that natural foci of TBEV may either persist at low levels of activity for years or reemerge through the agency of migrating birds. PMID- 25110672 TI - Noninvasive and quantitative assessment of in vivo fetomaternal interface angiogenesis using RGD-based fluorescence. AB - Angiogenesis is a key process for proper placental development and for the success of pregnancy. Although numerous in vitro methods have been developed for the assessment of this process, relatively few reliable in vivo methods are available to evaluate this activity throughout gestation. Here we report an in vivo technique that specifically measures placental neovascularization. The technique is based on the measurement of a fluorescent alpha v beta 3 (alphavbeta3) integrin-targeting molecule called Angiolone-Alexa-Fluor 700. The alphavbeta3 integrin is highly expressed by endothelial cells during the neovascularization and by trophoblast cells during their invasion of the maternal decidua. Angiolone was injected to gravid mice at 6.5 and 11.5 days post coitus (dpc). The fluorescence was analyzed one day later at 7.5 and 12.5 dpc, respectively. We demonstrated that (i) Angiolone targets alphavbeta3 protein in the placenta with a strong specificity, (ii) this technique is quantitative as the measurement was correlated to the increase of the placental size observed with increasing gestational age, and (iii) information on the outcome is possible, as abnormal placentation could be detected early on during gestation. In conclusion, we report the validation of a new noninvasive and quantitative method to assess the placental angiogenic activity, in vivo. PMID- 25110673 TI - The effect of maternal healthcare on the probability of child survival in Azerbaijan. AB - This study assesses the effects of maternal healthcare on child survival by using nonrandomized data from a cross-sectional survey in Azerbaijan. Using 2SLS and simultaneous equation bivariate probit models, we estimate the effects of delivering in healthcare facility on probability of child survival taking into account self-selection into the treatment. For women who delivered at healthcare facilities, the probability of child survival increases by approximately 18%. Furthermore, if every woman had the opportunity to deliver in healthcare facility, then the probability of child survival in Azerbaijan as a whole would have increased by approximately 16%. PMID- 25110675 TI - Changes in cortical thickness in 6-year-old children open their mind to a global vision of the world. AB - Even if objectively presented with similar visual stimuli, children younger than 6 years of age exhibit a strong attraction to local visual information (e.g., the trees), whereas children older than 6 years of age, similar to adults, exhibit a visual bias toward global information (e.g., the forest). Here, we studied the cortical thickness changes that underlie this bias shift from local to global visual information. Two groups, matched for age, gender, and handedness, were formed from a total of 30 children who were 6 years old, and both groups performed a traditional global/local visual task. The first group presented a local visual bias, and the other group presented a global visual bias. The results indicated that, compared with the local visual bias group, children with a global visual bias exhibited (1) decreased cortical thickness in the bilateral occipital regions and (2) increased cortical thickness in the left frontoparietal regions. These findings constitute the first structural study that supports the view that both synaptic pruning (i.e., decreased cortical thickness) and expansion mechanisms (i.e., increased cortical thickness) cooccur to allow healthy children to develop a global perception of the visual world. PMID- 25110676 TI - Radiosynthesis of [18)F]trifluoroalkyl groups: scope and limitations. AB - The present paper is concerned with radiochemical methodology to furnish the trifluoromethyl motif labelled with (18)F. Literature spanning the last four decades is comprehensively reviewed and radiochemical yields and specific activities are discussed. PMID- 25110674 TI - Role of lectin-like oxidized low density lipoprotein-1 in fetoplacental vascular dysfunction in preeclampsia. AB - The bioavailability of nitric oxide (NO) represents a key marker in vascular health. A decrease in NO induces a pathological condition denominated endothelial dysfunction, syndrome observed in different pathologies, such as obesity, diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE). PE is one of the major risks for maternal death and fetal loss. Recent studies suggest that the placenta of pregnant women with PE express high levels of lectin-like oxidized LDL receptor-1 (LOX-1), which induces endothelial dysfunction by increasing reactive oxygen species (ROS) and decreasing intracellular NO. Besides LOX-1 activation induces changes in migration and apoptosis of syncytiotrophoblast cells. However, the role of this receptor in placental tissue is still unknown. In this review we will describes the physiological roles of LOX 1 in normal placenta development and the potential involvement of this receptor in the pathophysiology of PE. PMID- 25110677 TI - Beneficial effects of testosterone therapy on functional capacity, cardiovascular parameters, and quality of life in patients with congestive heart failure. AB - BACKGROUND: According to the present evidences suggesting association between low testosterone level and prediction of reduced exercise capacity as well as poor clinical outcome in patients with heart failure, we sought to determine if testosterone therapy improves clinical and cardiovascular conditions as well as quality of life status in patients with stable chronic heart failure. METHODS: A total of 50 male patients who suffered from congestive heart failure were recruited in a double-blind, placebo-controlled trial and randomized to receive an intramuscular (gluteal) long-acting androgen injection (1 mL of testosterone enanthate 250 mg/mL) once every four weeks for 12 weeks or receive intramuscular injections of saline (1 mL of 0.9% wt/vol NaCl) with the same protocol. RESULTS: The changes in body weight, hemodynamic parameters, and left ventricular dimensional echocardiographic indices were all comparable between the two groups. Regarding changes in diastolic functional state and using Tei index, this parameter was significantly improved. Unlike the group received placebo, those who received testosterone had a significant increasing trend in 6-walk mean distance (6MWD) parameter within the study period (P = 0.019). The discrepancy in the trends of changes in 6MWD between study groups remained significant after adjusting baseline variables (mean square = 243.262, F index = 4.402, and P = 0.045). CONCLUSION: Our study strengthens insights into the beneficial role of testosterone in improvement of functional capacity and quality of life in heart failure patients. PMID- 25110678 TI - Effects of anti-TNF alpha drugs on disability in patients with rheumatoid arthritis: long-term real-life data from the Lorhen Registry. AB - This study involving 1033 patients with RA confirms the effectiveness of etanercept, adalimumab, and infliximab in reducing RA-related disability even in patients with a history of highly active and longstanding RA. Moreover, we found that the improvement in disability was biphasic, with a marked improvement during the first year of anti-TNF therapy, followed by slower but significant recovery over the subsequent four years. PMID- 25110679 TI - Evaluation of macular retinal ganglion cell-inner plexiform layer thickness after vitrectomy with internal limiting membrane peeling for idiopathic macular holes. AB - PURPOSE: To evaluate macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness changes after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole repair using a high-resolution spectral domain optical coherence tomography (SD-OCT). METHODS: 32 eyes from 32 patients with idiopathic macular holes who underwent vitrectomy with internal limiting membrane peeling between January 2011 and July 2012 were retrospectively analyzed. GCIPL thickness was measured before surgery, and at one month and at six months after surgery. Values obtained from automated and semimanual SD-OCT segmentation analysis were compared (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA). RESULTS: No significant differences were found between average GCIPL thickness values between preoperative and postoperative analysis. However, statistical significant differences were found in GCIPL thickness at the temporal macular quadrants at six months after surgery. Quality measurement analysis performed by automated segmentation revealed a significant number of segmentation errors. Semimanual segmentation slightly improved the quality of the results. CONCLUSION: SD-OCT analysis of GCIPL thickness found a significant reduction at the temporal macular quadrants at 6 months after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole. PMID- 25110680 TI - Specific growth rate determines the sensitivity of Escherichia coli to lactic acid stress: implications for predictive microbiology. AB - This study tested the hypothesis that sensitivity of Escherichia coli to lactic acid at concentrations relevant for fermented sausages (pH 4.6, 150 mM lactic acid, aw = 0.92, temperature = 20 or 27 degrees C) increases with increasing growth rate. For E. coli strain 683 cultured in TSB in chemostat or batch, subsequent inactivation rates when exposed to lactic acid stress increased with increasing growth rate at harvest. A linear relationship between growth rate at harvest and inactivation rate was found to describe both batch and chemostat cultures. The maximum difference in T90, the estimated times for a one-log reduction, was 10 hours between bacteria harvested during the first 3 hours of batch culture, that is, at different growth rates. A 10-hour difference in T90 would correspond to measuring inactivation at 33 degrees C or 45 degrees C instead of 37 degrees C based on relationships between temperature and inactivation. At similar harvest growth rates, inactivation rates were lower for bacteria cultured at 37 degrees C than at 15-20 degrees C. As demonstrated for E. coli 683, culture conditions leading to variable growth rates may contribute to variable lactic acid inactivation rates. Findings emphasize the use and reporting of standardised culture conditions and can have implications for the interpretation of data when developing inactivation models. PMID- 25110681 TI - Healing efficacy of an EGF impregnated triple gel based wound dressing: in vitro and in vivo studies. AB - To accomplish an ideal wound healing process which promotes healthy tissue growth with less scaring, a novel gel based topical drug delivery system composed of 3 different polymers chitosan, dextran sulfate, and polyvinylpyrrolidone K30 (CDP) was prepared. The physicochemical properties of the prepared gels were investigated in vitro. Gels showed a maximum swelling ratio of 50 +/- 1.95 times of dried gel in PBS at pH 7.4. The swelling ratios increase in acidic and alkaline pH to 55.3 +/- 1.75 and 65.5 +/- 2.42, respectively. In the rheological test, prepared gels revealed viscoelastic properties and a small linear viscoelastic region of 0.166%. In vivo wound healing promoting activities of CDP gels containing 20 MUg/mL EGF were evaluated on surgically induced dermal wounds in rats using pathologic examination. The application of CDP gel with incorporated EGF significantly reduced the defect on the rat's skin and enhanced epithelial healing compared with the topical application of the EGF-free CDP gel. The results clearly substantiate the beneficial effects of the topical application of CDP containing EGF in the acceleration of healthy wound healing process with less scarring. PMID- 25110682 TI - Induction of boosted immune response in mice by leptospiral surface proteins expressed in fusion with DnaK. AB - Leptospirosis is an important global disease of human and veterinary concern. Caused by pathogenic Leptospira, the illness was recently classified as an emerging infectious disease. Currently available veterinarian vaccines do not induce long-term protection against infection and do not provide cross-protective immunity. Several studies have suggested the use of DnaK as an antigen in vaccine formulation, due to an exceptional degree of immunogenicity. We focused on four surface proteins: rLIC10368 (Lsa21), rLIC10494, rLIC12690 (Lp95), and rLIC12730, previously shown to be involved in host-pathogen interactions. Our goal was to evaluate the immunogenicity of the proteins genetically fused with DnaK in animal model. The chosen genes were amplified by PCR methodology and cloned into pAE, an E. coli vector. The recombinant proteins were expressed alone or in fusion with DnaK at the N-terminus. Our results demonstrate that leptospiral proteins fused with DnaK have elicited an enhanced immune response in mice when compared to the effect promoted by the individual proteins. The boosted immune effect was demonstrated by the production of total IgG, lymphocyte proliferation, and significant amounts of IL-10 in supernatant of splenocyte cell cultures. We believe that this approach could be employed in vaccines to enhance presentation of antigens of Leptospira to professional immune cells. PMID- 25110683 TI - Potential use of halophytes to remediate saline soils. AB - Salinity is one of the rising problems causing tremendous yield losses in many regions of the world especially in arid and semiarid regions. To maximize crop productivity, these areas should be brought under utilization where there are options for removing salinity or using the salt-tolerant crops. Use of salt tolerant crops does not remove the salt and hence halophytes that have capacity to accumulate and exclude the salt can be an effective way. Methods for salt removal include agronomic practices or phytoremediation. The first is cost- and labor-intensive and needs some developmental strategies for implication; on the contrary, the phytoremediation by halophyte is more suitable as it can be executed very easily without those problems. Several halophyte species including grasses, shrubs, and trees can remove the salt from different kinds of salt affected problematic soils through salt excluding, excreting, or accumulating by their morphological, anatomical, physiological adaptation in their organelle level and cellular level. Exploiting halophytes for reducing salinity can be good sources for meeting the basic needs of people in salt-affected areas as well. This review focuses on the special adaptive features of halophytic plants under saline condition and the possible ways to utilize these plants to remediate salinity. PMID- 25110684 TI - Feasibility study of a hand guided robotic drill for cochleostomy. AB - The concept of a hand guided robotic drill has been inspired by an automated, arm supported robotic drill recently applied in clinical practice to produce cochleostomies without penetrating the endosteum ready for inserting cochlear electrodes. The smart tactile sensing scheme within the drill enables precise control of the state of interaction between tissues and tools in real-time. This paper reports development studies of the hand guided robotic drill where the same consistent outcomes, augmentation of surgeon control and skill, and similar reduction of induced disturbances on the hearing organ are achieved. The device operates with differing presentation of tissues resulting from variation in anatomy and demonstrates the ability to control or avoid penetration of tissue layers as required and to respond to intended rather than involuntary motion of the surgeon operator. The advantage of hand guided over an arm supported system is that it offers flexibility in adjusting the drilling trajectory. This can be important to initiate cutting on a hard convex tissue surface without slipping and then to proceed on the desired trajectory after cutting has commenced. The results for trials on phantoms show that drill unit compliance is an important factor in the design. PMID- 25110686 TI - Dehydroabietic acid derivative QC2 induces oncosis in hepatocellular carcinoma cells. AB - AIM: Rosin, the traditional Chinese medicine, is reported to be able to inhibit skin cancer cell lines. In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid. METHODS: MTT assay was used to determine the cytotoxicity of QC2. Morphological changes were observed by time-lapse microscopy and transmission electron microscopy and the cytoskeleton changes were observed by laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase (LDH), and mitochondrial membrane potential (Deltapsim). The underlying mechanism was manifested by Western blotting. The oncotic cell death was further confirmed by detection of oncosis related protein calpain. RESULTS: Swelling cell type and destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage was visualized by transmission electron microscopy. The detection of ROS accumulation, increased LDH release, and decreased ATP and Deltapsim confirmed the cell death. The oncotic related protein calpain was found to increase time dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the cytotoxicity. CONCLUSIONS: Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells. PMID- 25110687 TI - Characteristics and prediction of RNA structure. AB - RNA secondary structures with pseudoknots are often predicted by minimizing free energy, which is NP-hard. Most RNAs fold during transcription from DNA into RNA through a hierarchical pathway wherein secondary structures form prior to tertiary structures. Real RNA secondary structures often have local instead of global optimization because of kinetic reasons. The performance of RNA structure prediction may be improved by considering dynamic and hierarchical folding mechanisms. This study is a novel report on RNA folding that accords with the golden mean characteristic based on the statistical analysis of the real RNA secondary structures of all 480 sequences from RNA STRAND, which are validated by NMR or X-ray. The length ratios of domains in these sequences are approximately 0.382L, 0.5L, 0.618L, and L, where L is the sequence length. These points are just the important golden sections of sequence. With this characteristic, an algorithm is designed to predict RNA hierarchical structures and simulate RNA folding by dynamically folding RNA structures according to the above golden section points. The sensitivity and number of predicted pseudoknots of our algorithm are better than those of the Mfold, HotKnots, McQfold, ProbKnot, and Lhw-Zhu algorithms. Experimental results reflect the folding rules of RNA from a new angle that is close to natural folding. PMID- 25110685 TI - New insight into adiponectin role in obesity and obesity-related diseases. AB - Obesity is a major health problem strongly increasing the risk for various severe related complications such as metabolic syndrome, cardiovascular diseases, respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an endocrine organ that produces biologically active molecules defined "adipocytokines," protein hormones with pleiotropic functions involved in the regulation of energy metabolism as well as in appetite, insulin sensitivity, inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat accumulation causes dysregulation of adipokine production that strongly contributes to the onset of obesity-related diseases. Several advances have been made in the treatment and prevention of obesity but current medical therapies are often unsuccessful even in compliant patients. Among the adipokines, adiponectin shows protective activity in various processes such as energy metabolism, inflammation, and cell proliferation. In this review, we will focus on the current knowledge regarding the protective properties of adiponectin and its receptors, AdipoRs ("adiponectin system"), on metabolic complications in obesity and obesity-related diseases. Adiponectin, exhibiting antihyperglycemic, antiatherogenic, and anti-inflammatory properties, could have important clinical benefits in terms of development of therapies for the prevention and/or for the treatment of obesity and obesity-related diseases. PMID- 25110688 TI - Expression profiling of abiotic stress-inducible genes in response to multiple stresses in rice (Oryza sativa L.) varieties with contrasting level of stress tolerance. AB - The present study considered transcriptional profiles and protein expression analyses from shoot and/or root tissues under three abiotic stress conditions, namely, salinity, dehydration, and cold, as well as following exogenous abscisic acid treatment, at different time points of stress exposure in three indica rice varieties, IR-29 (salt sensitive), Pokkali, and Nonabokra (both salt tolerant). The candidate genes chosen for expression studies were HKT-1, SOS-3, NHX-1, SAPK5, SAPK7, NAC-1, Rab16A, OSBZ8, DREBP2, CRT/DREBP, WRKY24, and WRKY71, along with the candidate proteins OSBZ8, SAMDC, and GST. Gene expression profile revealed considerable differences between the salt-sensitive and salt-tolerant rice varieties, as the expression in the latter was higher even at the constitutive level, whereas it was inducible only by corresponding stress signals in IR-29. Whether in roots or shoots, the transcriptional responses to different stressors peaked following 24 h of stress/ABA exposure, and the transcript levels enhanced gradually with the period of exposure. The generality of stress responses at the transcriptional level was therefore time dependent. Heat map data also showed differential transcript abundance in the three varieties, correlating the observation with transcript profiling. In silico analysis of the upstream regions of all the genes represented the existence of conserved sequence motifs in single or multiple copies that are indispensable to abiotic stress response. Overall, the transcriptome and proteome analysis undertaken in the present study indicated that genes/proteins conferring tolerance, belonging to different functional classes, were overrepresented, thus providing novel insight into the functional basis of multiple stress tolerance in indica rice varieties. The present work will pave the way in future to select gene(s) for overexpression, so as to generate broad spectrum resistance to multiple stresses simultaneously. PMID- 25110689 TI - Production of conjugated linoleic and conjugated alpha-linolenic acid in a reconstituted skim milk-based medium by bifidobacterial strains isolated from human breast milk. AB - Eight bifidobacterial strains isolated from human breast milk have been tested for their abilities to convert linoleic acid (LA) and alpha-linolenic acid (LNA) to conjugated linoleic acid (CLA) and conjugated alpha-linolenic acid (CLNA), respectively. These bioactive lipids display important properties that may contribute to the maintenance and improvement human health. Three selected Bifidobacterium breve strains produced CLA from LA and CLNA from LNA in MRS (160 170 and 210-230 MUg mL(-1), resp.) and, also, in reconstituted skim milk (75-95 and 210-244 MUg mL(-1), resp.). These bifidobacterial strains were also able to simultaneously produce both CLA (90-105 MUg mL(-1)) and CLNA (290-320 MUg mL(-1)) in reconstituted skim milk. Globally, our findings suggest that these bifidobacterial strains are potential candidates for the design of new fermented dairy products naturally containing very high concentrations of these bioactive lipids. To our knowledge, this is the first study describing CLNA production and coproduction of CLA and CLNA by Bifidobacterium breve strains isolated from human milk in reconstituted skim milk. PMID- 25110690 TI - Investigation of the interaction between patulin and human serum albumin by a spectroscopic method, atomic force microscopy, and molecular modeling. AB - The interaction of patulin with human serum albumin (HSA) was studied in vitro under normal physiological conditions. The study was performed using fluorescence, ultraviolet-visible spectroscopy (UV-Vis), circular dichroism (CD), atomic force microscopy (AFM), and molecular modeling techniques. The quenching mechanism was investigated using the association constants, the number of binding sites, and basic thermodynamic parameters. A dynamic quenching mechanism occurred between HSA and patulin, and the binding constants (K) were 2.60 * 10(4), 4.59 * 10(4), and 7.01 * 10(4) M(-1) at 288, 300, and 310 K, respectively. Based on fluorescence resonance energy transfer, the distance between the HSA and patulin was determined to be 2.847 nm. The DeltaG (0), DeltaH (0), and DeltaS (0) values across various temperatures indicated that hydrophobic interaction was the predominant binding force. The UV-Vis and CD results confirmed that the secondary structure of HSA was altered in the presence of patulin. The AFM results revealed that the individual HSA molecule dimensions were larger after interaction with patulin. In addition, molecular modeling showed that the patulin-HSA complex was stabilized by hydrophobic and hydrogen bond forces. The study results suggested that a weak intermolecular interaction occurred between patulin and HSA. Overall, the results are potentially useful for elucidating the toxigenicity of patulin when it is combined with the biomolecular function effect, transmembrane transport, toxicological, testing and other experiments. PMID- 25110691 TI - Advanced user interfaces for neurorehabilitation. PMID- 25110693 TI - Effect of duplicate genes on mouse genetic robustness: an update. AB - In contrast to S. cerevisiae and C. elegans, analyses based on the current knockout (KO) mouse phenotypes led to the conclusion that duplicate genes had almost no role in mouse genetic robustness. It has been suggested that the bias of mouse KO database toward ancient duplicates may possibly cause this knockout duplicate puzzle, that is, a very similar proportion of essential genes (PE) between duplicate genes and singletons. In this paper, we conducted an extensive and careful analysis for the mouse KO phenotype data and corroborated a strong effect of duplicate genes on mouse genetics robustness. Moreover, the effect of duplicate genes on mouse genetic robustness is duplication-age dependent, which holds after ruling out the potential confounding effect from coding-sequence conservation, protein-protein connectivity, functional bias, or the bias of duplicates generated by whole genome duplication (WGD). Our findings suggest that two factors, the sampling bias toward ancient duplicates and very ancient duplicates with a proportion of essential genes higher than that of singletons, have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic buffering may be correlated with sequence conservation as well as protein-protein interactivity. PMID- 25110694 TI - Emotion recognition pattern in adolescent boys with attention deficit/hyperactivity disorder. AB - BACKGROUND: Social and emotional deficits were recently considered as inherent features of individuals with attention-deficit hyperactivity disorder (ADHD), but only sporadic literature data exist on emotion recognition in adolescents with ADHD. The aim of the present study was to establish emotion recognition profile in adolescent boys with ADHD in comparison with control adolescents. METHODS: Forty-four adolescent boys (13-16 years) participated in the study after informed consent; 22 boys had a clinical diagnosis of ADHD, while data were also assessed from 22 adolescent control boys matched for age and Raven IQ. Parent- and self reported behavioral characteristics were assessed by the means of the Strengths and Difficulties Questionnaire. The recognition of six basic emotions was evaluated by the "Facial Expressions of Emotion-Stimuli and Tests." RESULTS: Compared to controls, adolescents with ADHD were more sensitive in the recognition of disgust and, worse in the recognition of fear and showed a tendency for impaired recognition of sadness. Hyperactivity measures showed an inverse correlation with fear recognition. CONCLUSION: Our data suggest that adolescent boys with ADHD have alterations in the recognition of specific emotions. PMID- 25110695 TI - Prolonged sleep deprivation and continuous exercise: effects on melatonin, tympanic temperature, and cognitive function. AB - The purpose of this study was to examine tympanic temperature, melatonin, and cognitive function during a 36-hour endurance event. Nine male and three female participants took part in a 36-hour sustained endurance event without sleep (N = 12, mean age = 31.8 +/- 5.0 yrs). Participants were stopped for data collection at checkpoints throughout the 36-hour event. Tympanic temperature was assessed, a psychomotor vigilance test (PVT) was administered, and saliva samples were collected. Salivary melatonin was determined via immunoassay. During the 36 hours of competition, melatonin levels were negatively correlated with the day of the race (rs = -0.277, P = 0.039) and positively associated with nighttime (rs = 0.316, P = 0.021). Significant main effects of tympanic temperature (P < 0.001), day of the competition (P = 0.018), and a tympanic temperature * day of competition interaction (P < 0.001) were used to predict minor lapses in attention. No associations between melatonin levels and cognitive function were observed (P > 0.05). During the event tympanic temperature declined and was associated with an increase in lapses in attention. With sustained endurance events becoming more popular future research is warranted to evaluate the physiological impact of participation. PMID- 25110696 TI - Connexin 43 expression on peripheral blood eosinophils: role of gap junctions in transendothelial migration. AB - Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx)43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation. PMID- 25110697 TI - Magnetic resonance spectroscopy in the diagnosis of dementia with Lewy bodies. AB - Dementia with Lewy bodies (DLB) is considered to be the second most frequent primary degenerative dementing illness after Alzheimer's disease (AD). DLB, together with Parkinson's disease (PD), Parkinson's disease with dementia (PDD) belong to alpha-synucleinopathies--a group of neurodegenerative diseases associated with pathological accumulation of the alpha-synuclein protein. Dementia due to PD and DLB shares clinical symptoms and neuropsychological profiles. Moreover, the core features and additional clinical signs and symptoms for these two very similar diseases are largely the same. Neuroimaging seems to be a promising method in differential diagnosis of dementia studies. The development of imaging methods or other objective measures to supplement clinical criteria for DLB is needed and a method which would accurately facilitate diagnosis of DLB prior to death is still being searched. Proton magnetic resonance spectroscopy ((1)H-MRS) provides a noninvasive method of assessing an in vivo biochemistry of brain tissue. This review summarizes the main results obtained from the application of neuroimaging techniques in DLB cases focusing on (1)H-MRS. PMID- 25110698 TI - Upper limb posture estimation in robotic and virtual reality-based rehabilitation. AB - New motor rehabilitation therapies include virtual reality (VR) and robotic technologies. In limb rehabilitation, limb posture is required to (1) provide a limb realistic representation in VR games and (2) assess the patient improvement. When exoskeleton devices are used in the therapy, the measurements of their joint angles cannot be directly used to represent the posture of the patient limb, since the human and exoskeleton kinematic models differ. In response to this shortcoming, we propose a method to estimate the posture of the human limb attached to the exoskeleton. We use the exoskeleton joint angles measurements and the constraints of the exoskeleton on the limb to estimate the human limb joints angles. This paper presents (a) the mathematical formulation and solution to the problem, (b) the implementation of the proposed solution on a commercial exoskeleton system for the upper limb rehabilitation, (c) its integration into a rehabilitation VR game platform, and (d) the quantitative assessment of the method during elbow and wrist analytic training. Results show that this method properly estimates the limb posture to (i) animate avatars that represent the patient in VR games and (ii) obtain kinematic data for the patient assessment during elbow and wrist analytic rehabilitation. PMID- 25110699 TI - Cementless fixation of osteoporotic VCFs using titanium mesh implants (OsseoFix): preliminary results. AB - INTRODUCTION: Vertebral compression fractures (VCFs) affect 20% of people over the age of 70 with increasing incidence. Kypho-/vertebroplasty as standard operative procedures are associated with limitations like cement leakage, limited reduction capabilities, and risk for adjacent fractures. To address these shortcomings, we introduce a new minimal invasive cementless VCF fixation technique. METHODS: Four patients (72.3 years, range 70-76) with VCFs type AO/Muller A1.3 and concomitant osteoporosis were treated by minimal invasive transpedicular placement of two intervertebral mesh cages for fracture reduction and maintenance. Follow-up included functional/radiological assessment and clinical scores and averaged 27.7 months (24-28). RESULTS: Endplate reduction was achieved in all cases (mean surgery time: 28.5 minutes). Kyphotic (KA) and Cobb angle revealed considerable improvements postoperatively (KA 14.5 degrees to 10.7 degrees /Cobb 10.1 degrees to 8.3 degrees ). Slight loss of vertebral reduction (KA: 12.6 degrees ) and segment rekyphosis (Cobb: 10.7 degrees ) were observed for final follow-up. Pain improved from 8.8 to 2.8 (visual analogue scale). All cases showed signs of bony healing. No perioperative complications and no adjacent fractures occurred. CONCLUSION: Preliminary results in a small, selected patient collective indicate the ability of bony healing for osteoporotic VCFs. Cementless fixation using intravertebral titanium mesh cages revealed substantial pain relief, adequate reduction, and reduction maintenance without complications. Trial registration number is DRKS00005657, German Clinical Trials Register (DKRS). PMID- 25110692 TI - The role of chemoattractant receptors in shaping the tumor microenvironment. AB - Chemoattractant receptors are a family of seven transmembrane G protein coupled receptors (GPCRs) initially found to mediate the chemotaxis and activation of immune cells. During the past decades, the functions of these GPCRs have been discovered to not only regulate leukocyte trafficking and promote immune responses, but also play important roles in homeostasis, development, angiogenesis, and tumor progression. Accumulating evidence indicates that chemoattractant GPCRs and their ligands promote the progression of malignant tumors based on their capacity to orchestrate the infiltration of the tumor microenvironment by immune cells, endothelial cells, fibroblasts, and mesenchymal cells. This facilitates the interaction of tumor cells with host cells, tumor cells with tumor cells, and host cells with host cells to provide a basis for the expansion of established tumors and development of distant metastasis. In addition, many malignant tumors of the nonhematopoietic origin express multiple chemoattractant GPCRs that increase the invasiveness and metastasis of tumor cells. Therefore, GPCRs and their ligands constitute targets for the development of novel antitumor therapeutics. PMID- 25110701 TI - Significance of image guidance to clinical outcomes for localized prostate cancer. AB - PURPOSE: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with image-guided intensity-modulated radiotherapy (IG IMRT) and non-IGRT intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. MATERIALS AND METHODS: Between 2009 and 2012, 65 patients with localized prostate cancer were treated with IG-IMRT. This group of patients was retrospectively compared with a similar cohort of 62 patients who were treated between 2004 and 2009 with IMRT to the same dose without image guidance. RESULTS: The median follow-up time was 4.8 years. The rectal volume receiving >=40 and >=70 Gy was significantly lower in the IG-IMRT group. Grade 2 and higher acute and late GI and GU toxicity rates were lower in IG-IMRT group, but there was no statistical difference. No significant improvement in biochemical control at 5 years was observed in two groups. In a Cox regression analysis identifying predictors for PSA relapse-free survival, only preradiotherapy PSA was significantly associated with biochemical control; IG IMRT was not a statistically significant indicator. CONCLUSIONS: The use of image guidance in the radiation of prostate cancer at our institute did not show significant reduction in the rates of GI and GU toxicity and did not improve the biochemical control compared with IMRT. PMID- 25110700 TI - The harmful effects of subarachnoid hemorrhage on extracerebral organs. AB - Subarachnoid hemorrhage (SAH) is a devastating neurological disorder. Patients with aneurysmal SAH develop secondary complications that are important causes of morbidity and mortality. Aside from secondary neurological injuries, SAH has been associated with nonneurologic medical complications, such as neurocardiogenic injury, neurogenic pulmonary edema, hyperglycemia, and electrolyte imbalance, of which cardiac and pulmonary complications are most common. The related mechanisms include activation of the sympathetic nervous system, release of catecholamines and other hormones, and inflammatory responses. Extracerebral complications are directly related to the severity of SAH-induced brain injury and indicate the clinical outcome in patients. This review provides an overview of the extracerebral complications after SAH. We also aim to describe the manifestations, underlying mechanisms, and the effects of those extracerebral complications on outcome following SAH. PMID- 25110703 TI - Current evidence regarding prophylactic antibiotics in head and neck and maxillofacial surgery. AB - Antibiotic prophylaxis is commonly used to decrease the rate of infections in head and neck surgery. The aim of this paper is to present the available evidence regarding the application of antibiotic prophylaxis in surgical procedures of the head and neck region in healthy patients. A systemic literature review based on Medline and Embase databases was performed. All reviews and meta-analyses based on RCTs in English from 2000 to 2013 were included. Eight out of 532 studies fulfilled all requirements. Within those, only seven different operative procedures were analyzed. Evidence exists for the beneficial use of prophylactic antibiotics for tympanostomy, orthognathic surgery, and operative tooth extractions. Unfortunately, little high-level evidence exists regarding the use of prophylactic antibiotics in head and neck surgery. In numerous cases, no clear benefit of antibiotic prophylaxis has been shown, particularly considering their potential adverse side effects. Antibiotics are often given unnecessarily and are administered too late and for too long. Furthermore, little research has been performed on the large number of routine cases in the above-mentioned areas of specialization within the last few years, although questions arising with respect to the treatment of high-risk patients or of specific infections are discussed on a broad base. PMID- 25110702 TI - Immunocontraceptives: new approaches to fertility control. AB - The rapidly increasing global population has bowed the attention of family planning and associated reproductive health programmes in the direction of providing a safe and reliable method which can be used to limit family size. The world population is estimated to exceed a phenomenal 10 billion by the year 2050 A.D., thus presenting a real jeopardy of overpopulation with severe implications for the future. Despite the availability of contraceptive methods, there are over one million elective abortions globally each year due to unintended pregnancies, having devastating impact on reproductive health of women worldwide. This highlights the need for the development of newer and improved contraceptive methods. A novel contraceptive approach that is gaining substantial attention is "immunocontraception" targeting gamete production, gamete outcome, or gamete function. Amongst these, use of sperm antigens (gamete function) seems to be an exciting and feasible approach. However, the variability of immune response and time lag to attain titer among vaccinated individuals after active immunization has highlighted the potential relevance of preformed antibodies in this league. This review is an attempt to analyze the current status and progress of immunocontraceptive approaches with respect to their establishment as a future fertility control agent. PMID- 25110704 TI - Neurobiological mechanisms of pelvic pain. AB - Pelvic pain is a common condition which significantly deteriorates health-related quality of life. The most commonly identified causes of pain in the pelvic region are gynaecologic, urologic, gastrointestinal, neurological, and musculoskeletal. However, in up to 33% of patients the source of this symptom is not identified, frustrating both patients and health-care professionals. Pelvic pain may involve both the somatic and visceral systems, making the differential diagnosing challenging. This paper aimed to review the mechanisms involved in pelvic pain perception by analyzing the neural plasticity and molecules which are involved in these complex circuits. PMID- 25110705 TI - Cisplatin-based chemotherapy versus cetuximab in concurrent chemoradiotherapy for locally advanced head and neck cancer treatment. AB - BACKGROUND AND PURPOSE: This study aimed to analyze survival, clinical responses, compliance, and adverse effects in locally advanced head and neck cancer (LAHNC) patients treated with split-dose cisplatin-based concurrent chemoradiation therapy (SD-CCRT) or cetuximab with concurrent radiation therapy (BioRT). MATERIALS AND METHODS: We retrospectively evaluated 170 LAHNC patients diagnosed between January 1, 2009, and July 31, 2012: 116 received CCRT and 54 received BioRT. RESULTS: Complete response rates were similar in the SD-CCRT and BioRT groups (63.8% versus 59.3%; P = 0.807), and locoregional relapse rates were 18.1% and 13.0%, respectively (P = 0.400). The 3-year relapse-free survival rate was 65.8% in the SD-CCRT group and 65.5% in the BioRT group, respectively (P = 0.647). The 3-year overall survival rate was 78.5% in the SD-CCRT group and 70.9% in the BioRT group, respectively (P = 0.879). Hematologic side effects were significantly more frequent in the SD-CCRT than in the BioRT group. Mucositis frequency was similar. CONCLUSIONS: Primary SD-CCRT and BioRT both showed good clinical response and survival. Hematologic toxicities were more frequent, but tolerable, in the SD-CCRT group. Both groups showed good compliance. PMID- 25110706 TI - Cardiac troponin T (TNNT2) mutations in chinese dilated cardiomyopathy patients. AB - BACKGROUND: Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. Although more than 40 genes have been reported to cause DCM, the role of genetic testing in clinical practice is not well defined. Mutations in the troponin T (TNNT2) gene represent an important subset of known disease-causing mutations associated with DCM. Therefore, the aim of the present study was to determine the genetic variations in TNNT2 and the associations of those variations with DCM in Chinese patients. METHODS: An approximately 4 kb fragment of the TNNT2 gene was isolated from 103 DCM patients and 192 healthy controls and was analyzed by DNA sequence analysis for genetic variations. RESULTS: A total of 6 TNNT2 mutations were identified in 99 patients, including a G321T missense mutation (Leu84Phe) and 5 novel intronic mutations. Alleles of two novel SNPs (c.192 + 353 C>A, OR = 0.095, 95% CI: 0.013-0.714, P = 0.022; c.192 + 463 G>A, OR = 0.090, 95% CI: 0.012-0.675, P = 0.019) and SNP rs3729843 (OR = 1.889, 95% CI: 1.252-2.852; P = 0.002) were significantly correlated with DCM. CONCLUSIONS: These results suggest that the missense mutation (Leu84Phe) and two novel SNPs (c.192 + 353 C>A, c.192 + 463 G>A) in TNNT2 gene might be associated with DCM in the Chinese population. PMID- 25110707 TI - Acute and long-term effects of noise exposure on the neuronal spontaneous activity in cochlear nucleus and inferior colliculus brain slices. AB - Noise exposure leads to an immediate hearing loss and is followed by a long lasting permanent threshold shift, accompanied by changes of cellular properties within the central auditory pathway. Electrophysiological recordings have demonstrated an upregulation of spontaneous neuronal activity. It is still discussed if the observed effects are related to changes of peripheral input or evoked within the central auditory system. The present study should describe the intrinsic temporal patterns of single-unit activity upon noise-induced hearing loss of the dorsal and ventral cochlear nucleus (DCN and VCN) and the inferior colliculus (IC) in adult mouse brain slices. Recordings showed a slight, but significant, elevation in spontaneous firing rates in DCN and VCN immediately after noise trauma, whereas no differences were found in IC. One week postexposure, neuronal responses remained unchanged compared to controls. At 14 days after noise trauma, intrinsic long-term hyperactivity in brain slices of the DCN and the IC was detected for the first time. Therefore, increase in spontaneous activity seems to develop within the period of two weeks, but not before day 7. The results give insight into the complex temporal neurophysiological alterations after noise trauma, leading to a better understanding of central mechanisms in noise-induced hearing loss. PMID- 25110708 TI - A review on the traditional Chinese medicinal herbs and formulae with hypolipidemic effect. AB - Hyperlipidemia, characterized by the abnormal blood lipid profiles, is one of the dominant factors of many chronic diseases such as diabetes, obesity, and cardiovascular diseases (CVD). For the low cost, effectiveness, and fewer side effects, the popularity of using traditional Chinese medicine (TCM) to handle hyperlipidemia is increasing and its role in health care has been recognized by the public at large. Despite the importance of TCM herbs and formulations, there is no comprehensive review summarizing their scientific findings on handling hyperlipidemia. This review summarizes the recent experimental and clinical results of nine representative single Chinese herbs and seven classic TCM formulae that could improve lipid profiles so as to help understand and compare their underlying mechanisms. Most of single herbs and formulae demonstrated the improvement of hyperlipidemic conditions with multiple and diverse mechanisms of actions similar to conventional Western drugs in spite of their mild side effects. Due to increasing popularity of TCM, more extensive, well-designed preclinical and clinical trials on the potential synergistic and adverse side effects of herb-drug interactions as well as their mechanisms are warranted. Hyperlipidemic patients should be warned about the potential risks of herb-drug interactions, particularly those taking anticoagulants and antiplatelet drugs. PMID- 25110710 TI - Amplification of the insulin-like growth factor 1 receptor gene is a rare event in adrenocortical adenocarcinomas: searching for potential mechanisms of overexpression. AB - CONTEXT: IGF1R overexpression appears to be a prognostic biomarker of metastatic pediatric adrenocortical tumors. However, the molecular mechanisms that are implicated in its upregulation remain unknown. Aim. To investigate the potential mechanisms involved in IGF1R overexpression. PATIENTS AND METHODS: We studied 64 adrenocortical tumors. IGF1R copy number variation was determined in all patients using MLPA and confirmed using real time PCR. In a subgroup of 32 patients, automatic sequencing was used to identify IGF1R allelic variants and the expression of microRNAs involved in IGF1R regulation by real time PCR. RESULTS: IGF1R amplification was detected in an adrenocortical carcinoma that was diagnosed in a 46-year-old woman with Cushing's syndrome and virilization. IGF1R overexpression was demonstrated in this case. In addition, gene amplification of other loci was identified in this adrenocortical malignant tumor, but no IGF1R copy number variation was evidenced in the remaining cases. Automatic sequencing revealed three known polymorphisms but they did not correlate with its expression. Expression of miR-100, miR-145, miR-375, and miR-126 did not correlate with IGF1R expression. CONCLUSION: We demonstrated amplification and overexpression of IGF1R gene in only one adrenocortical carcinoma, suggesting that these combined events are uncommon. In addition, IGF1R polymorphisms and abnormal microRNA expression did not correlate with IGF1R upregulation in adrenocortical tumors. PMID- 25110709 TI - The impact of simulated and real microgravity on bone cells and mesenchymal stem cells. AB - How microgravity affects the biology of human cells and the formation of 3D cell cultures in real and simulated microgravity (r- and s-ug) is currently a hot topic in biomedicine. In r- and s-ug, various cell types were found to form 3D structures. This review will focus on the current knowledge of tissue engineering in space and on Earth using systems such as the random positioning machine (RPM), the 2D-clinostat, or the NASA-developed rotating wall vessel bioreactor (RWV) to create tissue from bone, tumor, and mesenchymal stem cells. To understand the development of 3D structures, in vitro experiments using s-ug devices can provide valuable information about modulations in signal-transduction, cell adhesion, or extracellular matrix induced by altered gravity conditions. These systems also facilitate the analysis of the impact of growth factors, hormones, or drugs on these tissue-like constructs. Progress has been made in bone tissue engineering using the RWV, and multicellular tumor spheroids (MCTS), formed in both r- and s ug, have been reported and were analyzed in depth. Currently, these MCTS are available for drug testing and proteomic investigations. This review provides an overview of the influence of ug on the aforementioned cells and an outlook for future perspectives in tissue engineering. PMID- 25110711 TI - The K-Cl cotransporter KCC3 as an independent prognostic factor in human esophageal squamous cell carcinoma. AB - The objectives of the present study were to investigate the role of K-Cl cotransporter 3 (KCC3) in the regulation of cellular invasion and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC). Immunohistochemical analysis performed on 70 primary tumor samples obtained from ESCC patients showed that KCC3 was primarily found in the cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor (MT) was related to several clinicopathological features, such as the pT and pN categories, it had no prognostic impact. KCC3 expression scores were compared between the MT and cancer nest (CN), and the survival rate of patients with a CN > MT score was lower than that of patients with a CN <= MT score. In addition, the survival rate of patients in whom KCC3 was expressed in the invasive front of tumor was lower than that of the patients without it. Furthermore, multivariate analysis demonstrated that the expression of KCC3 in the invasive front was one of the most important independent prognostic factors. The depletion of KCC3 using siRNAs inhibited cell migration and invasion in human ESCC cell lines. These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC. PMID- 25110712 TI - The tarsal bone test: a basic test of health sciences students' knowledge of lower limb anatomy. AB - OBJECTIVES: The aim of the present study was to design an easy-to-use tool, the tarsal bone test (TBT), to provide a snapshot of podiatry students' basic anatomical knowledge of the bones of the lower limb. METHODS: The study included 254 podiatry students from three different universities, 145 of them were first year students and 109 were in their fourth and final years. The TBT was administered without prior notice to the participants and was to be completed in 5 minutes. RESULTS: The results show that 97.2% of the subjects (n = 247) correctly labelled all tarsal bones, while the other 2.8% (n = 7) incorrectly labelled at least one bone, that was either the cuboid (7 times) or the navicular (6 times). Although only one fourth-year student inaccurately identified one bone, no significant differences in the distribution of the correct and incorrect responses were found between first and fourth-year students. CONCLUSIONS: The TBT seems to be a straightforward and easy-to-apply instrument, and provides an objective view of the level of knowledge acquired at different stages of podiatry studies. PMID- 25110713 TI - Perinatal nitric oxide therapy prevents adverse effects of perinatal hypoxia on the adult pulmonary circulation. AB - Adverse events in utero are associated with the occurrence of chronic diseases in adulthood. We previously demonstrated in mice that perinatal hypoxia resulted in altered pulmonary circulation in adulthood, with a decreased endothelium dependent relaxation of pulmonary arteries, associated with long-term alterations in the nitric oxide (NO)/cyclic GMP pathway. The present study investigated whether inhaled NO (iNO) administered simultaneously to perinatal hypoxia could have potential beneficial effects on the adult pulmonary circulation. Indeed, iNO is the therapy of choice in humans presenting neonatal pulmonary hypertension. Long-term effects of neonatal iNO therapy on adult pulmonary circulation have not yet been investigated. Pregnant mice were placed in hypoxia (13% O2) with simultaneous administration of iNO 5 days before delivery until 5 days after birth. Pups were then raised in normoxia until adulthood. Perinatal iNO administration completely restored acetylcholine-induced relaxation, as well as endothelial nitric oxide synthase protein content, in isolated pulmonary arteries of adult mice born in hypoxia. Right ventricular hypertrophy observed in old mice born in hypoxia compared to controls was also prevented by perinatal iNO treatment. Therefore, simultaneous administration of iNO during perinatal hypoxic exposure seems able to prevent adverse effects of perinatal hypoxia on the adult pulmonary circulation. PMID- 25110714 TI - Incorporating amino acids composition and functional domains for identifying bacterial toxin proteins. AB - Aside from pathogenesis, bacterial toxins also have been used for medical purpose such as drugs for cancer and immune diseases. Correctly identifying bacterial toxins and their types (endotoxins and exotoxins) has great impact on the cell biology study and therapy development. However, experimental methods for bacterial toxins identification are time-consuming and labor-intensive, implying an urgent need for computational prediction. Thus, we are motivated to develop a method for computational identification of bacterial toxins based on amino acid sequences and functional domain information. In this study, a nonredundant dataset of 167 bacterial toxins including 77 exotoxins and 90 endotoxins is adopted to learn the predictive model by using support vector machines (SVMs). The cross-validation evaluation shows that the SVM models trained with amino acids and dipeptides composition could yield an accuracy of 96.07% and 92.50%, respectively. For discriminating endotoxins from exotoxins, the SVM models trained with amino acids and dipeptides composition have achieved an accuracy of 95.71% and 92.86%, respectively. After incorporating functional domain information, the predictive performance is further improved. The proposed method has been demonstrated to be able to more effectively identify and classify bacterial toxins than the other two features on independent dataset, which may aid in bacterial biomedical development. PMID- 25110715 TI - Antioxidant properties of mushroom mycelia obtained by batch cultivation and tocopherol content affected by extraction procedures. AB - The determination of the antioxidant potential of lyophilized mushroom mycelia from 5 strains of the species Pleurotus ostreatus and Coprinus comatus (obtained by submerged cultivation in batch system) was analyzed as ethanolic extracts by evaluating ABTS and the hydroxyl scavenging activity, FRAP method, the chelating capacity, the inhibition of human erythrocyte hemolysis, and the inhibition of xanthine oxidase activity. The main compounds present in all extracts were determined by HPLC chromatography. Overall, results demonstrated that the biologically active substances content is modulated by the extraction method used. The most beneficial extract, characterized by determining the EC50 value, was that of C. comatus M8102, followed by P. ostreatus PQMZ91109. Significant amount of alpha-tocopherol (179.51 +/- 1.51 mg/100 g extract) was determined as well as flavones such as rutin and apigenin. In the P. ostreatus PQMZ91109 extract, 4.8 +/- 0.05 mg/100 g extract of tocopherol acetate known to play a significant role as an antioxidant in skin protection against oxidative stress generated by UV rays was determined. The various correlations (r (2) = 0.7665 0.9426 for tocopherol content) assessed and the composition of extracts in fluidized bed from the mycelia of the tested species depicted a significant pharmacological potential as well as the possibility of usage in the development of new functional products. PMID- 25110716 TI - Influence of thread pitch, helix angle, and compactness on micromotion of immediately loaded implants in three types of bone quality: a three-dimensional finite element analysis. AB - This study investigated the influence of thread pitch, helix angle, and compactness on micromotion in immediately loaded implants in bone of varying density (D2, D3, and D4). Five models of the three-dimensional finite element (0.8 mm pitch, 1.6 mm pitch, 2.4 mm pitch, double-threaded, and triple-threaded implants) in three types of bone were created using Pro/E, Hypermesh, and ABAQUS software. The study had three groups: Group 1, different pitches (Pitch Group); Group 2, same compactness but different helix angles (Angle Group); and Group 3, same helix angle but different compactness (Compact Group). Implant micromotion was assessed as the comprehensive relative displacement. We found that vertical relative displacement was affected by thread pitch, helix angle, and compactness. Under vertical loading, displacement was positively correlated with thread pitch and helix angle but negatively with compactness. Under horizontal loading in D2, the influence of pitch, helix angle, and compactness on implant stability was limited; however, in D3 and D4, the influence of pitch, helix angle, and compactness on implant stability is increased. The additional evidence was provided that trabecular bone density has less effect on implant micromotion than cortical bone thickness. Bone type amplifies the influence of thread pattern on displacement. PMID- 25110718 TI - Operational Definitions of Sexual Orientation and Estimates of Adolescent Health Risk Behaviors. AB - PURPOSE: Increasing attention to the health of lesbian, gay, and bisexual (LGB) populations comes with requisite circumspection about measuring sexual orientation in surveys. However, operationalizing these variables also requires considerable thought. This research sought to document the consequences of different operational definitions of sexual orientation by examining variation in health risk behaviors. METHODS: Using Massachusetts Youth Risk Behavior Survey data, we examined how operational definitions of sexual behavior and sexual identity influenced differences among three health behaviors known to disparately affect LGB populations: smoking, suicide risk, and methamphetamine use. Sexual behavior and sexual identity were also examined together to explore if they captured unique sources of variability in behavior. RESULTS: Estimates of health disparities changed as a result of using either sexual behavior or sexual identity. Youth who reported their sexual identity as "not sure" also had increased odds of health risk behavior. Disaggregating bisexual identity and behavior from same-sex identity and behavior frequently resulted in the attenuation or elimination of health disparities that would have otherwise been attributable to exclusively same-sex sexual minorities. Finally, sexual behavior and sexual identity explained unique and significant sources of variability in all three health behaviors. CONCLUSION: Researchers using different operational definitions of sexual orientation could draw different conclusions, even when analyzing the same data, depending upon how they chose to represent sexual orientation in analyses. We discuss implications that these manipulations have on data interpretation and provide specific recommendations for best-practices when analyzing sexual orientation data collected from adolescent populations. PMID- 25110719 TI - Utility of Diagnostic Imaging in the Diagnosis and Management of Schistosomiasis. AB - Diagnosis of schistosomiasis is made by demonstration of the parasite ova in stools, urine,and biopsy specimens from affected organs, or presence of antibodies to the different stages of the parasite or antigens circulating in body fluids by serologic techniques. DNA of schistosomes can now also be detected in serum and stool specimens by molecular technique.However, these tests are unable to determine the severity of target organ pathology and resultant complications. Accurate assessment of schistosome-induced morbidities is now made with the use of imaging techniques like ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). US has made major contributions in the diagnosis of hepatosplenic and urinary form of disease. This imaging method provides real time results, is portable (can be carried to the bed side and the field) and is lower in cost than other imaging techniques. Typical findings in hepatosplenic schistosomiasis by US include: hyperechoic fibrotic bands along the portal vessels (Symmer's fibrosis), reduction in the size of the right lobe, hypertrophy of the left lobe, splenomegaly, and ascites. More advanced ultrasound equipment like the colour Doppler ultrasound can characterize portal vein perfusion, a procedure that is critical for the prediction of disease prognosis and for treatment options for complicated portal hypertension. Although CT and MRI are more expensive, are hospital based, and require highly additional specially-trained personnel, they provide more accurate description of the pathology, not only in hepatosplenic and urinary forms of schistosomiasis, but also in the diagnosis of ectopic forms of the disease,particularly involving thebrain and spinal cord. MRI demonstrates better tissue differentiation and lack of exposure to ionizing radiation compared with CT. PMID- 25110717 TI - TGF- beta: an important mediator of allergic disease and a molecule with dual activity in cancer development. AB - The transforming growth factor- beta (TGF- beta ) superfamily is a family of structurally related proteins that includes TGF- beta , activins/inhibins, and bone morphogenic proteins (BMPs). Members of the TGF- beta superfamily regulate cellular functions such as proliferation, apoptosis, differentiation, and migration and thus play key roles in organismal development. TGF- beta is involved in several human diseases, including autoimmune disorders and vascular diseases. Activation of the TGF- beta receptor induces phosphorylation of serine/threonine residues and triggers phosphorylation of intracellular effectors (Smads). Once activated, Smad proteins translocate to the nucleus and induce transcription of their target genes, regulating various processes and cellular functions. Recently, there has been an attempt to correlate the effect of TGF- beta with various pathological entities such as allergic diseases and cancer, yielding a new area of research known as "allergooncology," which investigates the mechanisms by which allergic diseases may influence the progression of certain cancers. This knowledge could generate new therapeutic strategies aimed at correcting the pathologies in which TGF- beta is involved. Here, we review recent studies that suggest an important role for TGF- beta in both allergic disease and cancer progression. PMID- 25110720 TI - Infections and inflammation in prostate cancer. AB - The frequent observation of both acute and chronic inflammation of unknown stimulus in the adult prostate has motivated a large body of research aimed at identifying potential infectious agents that may elicit prostatic inflammation. The overarching hypothesis is that infection-induced inflammation may be associated with prostate cancer development or progression, as inflammation is known to serve as an "enabling characteristic" of cancer. With recent advances in molecular techniques for microorganism identification, a panoply of microorganisms has been scrutinized in prostate tissues and in relation to prostate carcinogenesis. The aim of this review is to summarize the current literature on the evidence for infectious agents as a contributing factor to prostatic inflammation and prostate cancer, and to highlight recent literature suggesting an infectious etiology to the biogenesis of prostatic corpora amylacea and on the development of mouse models of prostatic infections. PMID- 25110722 TI - Facilitative and inhibitory effect of litter on seedling emergence and early growth of six herbaceous species in an early successional old field ecosystem. AB - In the current study, a field experiment was conducted to examine effects of litter on seedling emergence and early growth of four dominant weed species from the early successional stages of old field ecosystem and two perennial grassland species in late successional stages. Our results showed that increased litter cover decreased soil temperature and temperature variability over time and improved soil moisture status. Surface soil electrical conductivity increased as litter increased. The increased litter delayed seedling emergence time and rate. The emergence percentage of seedlings and establishment success rate firstly increased then decreased as litter cover increased. When litter biomass was below 600 g m(-2), litter increased seedlings emergence and establishment success in all species. With litter increasing, the basal diameter of seedling decreased, but seedling height increased. Increasing amounts of litter tended to increase seedling dry weight and stem leaf ratio. Different species responded differently to the increase of litter. Puccinellia tenuiflora and Chloris virgata will acquire more emergence benefits under high litter amount. It is predicted that Chloris virgata will dominate further in this natural succession old field ecosystem with litter accumulation. Artificial P. tenuiflora seeds addition may be required to accelerate old field succession toward matured grassland. PMID- 25110721 TI - Biomarker Development for Brain-Based Disorders: Recent Progress in Psychiatry. AB - Biomarkers are biological measures that are indicative of a specific disorder, its severity or response to treatment. They are widely used in many areas of medicine, but biomarker development for brain-based disorders lags behind. Using examples from the field of psychiatry, this article reviews the concepts of biomarkers, challenges to their development and the recent progress along those lines. In addition to discussing historical biomarker candidates such as cortisol or catecholamine levels, we include progress from recent genetic, epigenetic, proteomic, neuroimaging and EEG studies. Successful identification of biomarkers will advance the field of psychiatry towards the goal of biological tests for diagnosis, symptom management and treatment response. PMID- 25110724 TI - Gait signal analysis with similarity measure. AB - Human gait decision was carried out with the help of similarity measure design. Gait signal was selected through hardware implementation including all in one sensor, control unit, and notebook with connector. Each gait signal was considered as high dimensional data. Therefore, high dimensional data analysis was considered via heuristic technique such as the similarity measure. Each human pattern such as walking, sitting, standing, and stepping up was obtained through experiment. By the results of the analysis, we also identified the overlapped and nonoverlapped data relation, and similarity measure analysis was also illustrated, and comparison with conventional similarity measure was also carried out. Hence, nonoverlapped data similarity analysis provided the clue to solve the similarity of high dimensional data. Considered high dimensional data analysis was designed with consideration of neighborhood information. Proposed similarity measure was applied to identify the behavior patterns of different persons, and different behaviours of the same person. Obtained analysis can be extended to organize health monitoring system for specially elderly persons. PMID- 25110723 TI - Mitigative effect of erythromycin on PMMA challenged preosteoblastic MC3T3-E1 cells. AB - BACKGROUND: Aseptic loosening (AL) is a major complication of total joint replacement. Recent approaches to limiting AL have focused on inhibiting periprosthetic inflammation and osteoclastogenesis. QUESTIONS/PURPOSES: The purpose of this study was to determine the effects of erythromycin (EM) on polymethylmethacrylate (PMMA) particle-challenged MC3T3 osteoblast precursor cells. MetHODS: MC3T3 cells were pretreated with EM (0-10 MUg/mL) and then stimulated with PMMA (1 mg/mL). Cell viability was evaluated by both a lactate dehydrogenase (LDH) release assay and cell counts. Cell differentiation was determined by activity of alkaline phosphatase (ALP). Gene expression was measured via real-time quantitative RT-PCR. RESULTS: We found that exposure to PMMA particles reduced cellular viability and osteogenetic potential in MC3T3 cell line. EM treatment mitigated the effects of PMMA particles on the proliferation, viability and differentiation of MC3T3 cells. PMMA decreased the gene expression of Runx2, osterix and osteocalcin, which can be partially restored by EM treatment. Furthermore, EM suppressed PMMA- induced increase of NF kappaB gene expression. CONCLUSIONS: These data demonstrate that EM mitigates the effects of PMMA on MC3T3 cell viability and differentiation, in part through downregulation of NF-kappaB pathway. EM appeared to represent an anabolic agent on MC3T3 cells challenged with PMMA particles. PMID- 25110725 TI - Detecting community structures in networks by label propagation with prediction of percolation transition. AB - Though label propagation algorithm (LPA) is one of the fastest algorithms for community detection in complex networks, the problem of trivial solutions frequently occurring in the algorithm affects its performance. We propose a label propagation algorithm with prediction of percolation transition (LPAp). After analyzing the reason for multiple solutions of LPA, by transforming the process of community detection into network construction process, a trivial solution in label propagation is considered as a giant component in the percolation transition. We add a prediction process of percolation transition in label propagation to delay the occurrence of trivial solutions, which makes small communities easier to be found. We also give an incomplete update condition which considers both neighbor purity and the contribution of small degree vertices to community detection to reduce the computation time of LPAp. Numerical tests are conducted. Experimental results on synthetic networks and real-world networks show that the LPAp is more accurate, more sensitive to small community, and has the ability to identify a single community structure. Moreover, LPAp with the incomplete update process can use less computation time than LPA, nearly without modularity loss. PMID- 25110726 TI - Coal fly ash ceramics: preparation, characterization, and use in the hydrolysis of sucrose. AB - Coal ash is a byproduct of mineral coal combustion in thermal power plants. This residue is responsible for many environmental problems because it pollutes soil, water, and air. Thus, it is important to find ways to reuse it. In this study, coal fly ash, obtained from the Presidente Medici Thermal Power Plant, was utilized in the preparation of ceramic supports for the immobilization of the enzyme invertase and subsequent hydrolysis of sucrose. Coal fly ash supports were prepared at several compaction pressures (63.66-318.30 MPa) and sintered at 1200 degrees C for 4 h. Mineralogical composition (by X-ray diffraction) and surface area were studied. The ceramic prepared with 318.30 MPa presented the highest surface area (35 m(2)/g) and amount of immobilized enzyme per g of support (76.6 mg/g). In assays involving sucrose inversion, it showed a high degree of hydrolysis (around 81%) even after nine reuses and 30 days' storage. Therefore, coal fly ash ceramics were demonstrated to be a promising biotechnological alternative as an immobilization support for the hydrolysis of sucrose. PMID- 25110727 TI - Technology efficacy in active prosthetic knees for transfemoral amputees: a quantitative evaluation. AB - Several studies have presented technological ensembles of active knee systems for transfemoral prosthesis. Other studies have examined the amputees' gait performance while wearing a specific active prosthesis. This paper combined both insights, that is, a technical examination of the components used, with an evaluation of how these improved the gait of respective users. This study aims to offer a quantitative understanding of the potential enhancement derived from strategic integration of core elements in developing an effective device. The study systematically discussed the current technology in active transfemoral prosthesis with respect to its functional walking performance amongst above-knee amputee users, to evaluate the system's efficacy in producing close-to-normal user performance. The performances of its actuator, sensory system, and control technique that are incorporated in each reported system were evaluated separately and numerical comparisons were conducted based on the percentage of amputees' gait deviation from normal gait profile points. The results identified particular components that contributed closest to normal gait parameters. However, the conclusion is limitedly extendable due to the small number of studies. Thus, more clinical validation of the active prosthetic knee technology is needed to better understand the extent of contribution of each component to the most functional development. PMID- 25110728 TI - Scene consistency verification based on PatchNet. AB - In the real world, the object does not exist in isolation, and it always appears in a certain scene. Usually the object is fixed in a particular scene and even in special spatial location. In this paper, we propose a method for judging scene consistency effectively. Scene semantics and geometry relation play a key role. In this paper, we use PatchNet to deal with these high-level scene structures. We construct a consistent scene database, using semantic information of PatchNet to determine whether the scene is consistent. The effectiveness of the proposed algorithm is verified by a lot of experiments. PMID- 25110729 TI - Inference for one-way ANOVA with equicorrelation error structure. AB - We consider inferences in a one-way ANOVA model with equicorrelation error structures. Hypotheses of the equality of the means are discussed. A generalized F-test has been proposed by in the literature to compare the means of all populations. However, they did not discuss the performance of that test. We propose two methods, a generalized pivotal quantities-based method and a parametric bootstrap method, to test the hypotheses of equality of the means. We compare the empirical performance of the proposed tests with the generalized F test. It can be seen from the simulation results that the generalized F-test does not perform well in terms of Type I error rate, and the proposed tests perform much better. We also provide corresponding simultaneous confidence intervals for all pair-wise differences of the means, whose coverage probabilities are close to the confidence level. PMID- 25110730 TI - Enoxaparin prevents steroid-related avascular necrosis of the femoral head. AB - Nontraumatic osteonecrosis of the femoral head is still a challenging problem in orthopedic surgery. It is responsible for 10% of the 500,000 hip replacement surgeries in the USA and affects relatively young, active patients in particular. Main reasons for nontraumatic osteonecrosis are glucocorticoid use, alcoholism, thrombophilia, and hypofibrinolysis (Glueck et al., 1997; Orth and Anagnostakos, 2013). One pathomechanism of steroid-induced osteonecrosis is thought to be impaired blood flow to the femoral head caused by increased thrombus formation and vasoconstriction. To investigate the preventive effect of enoxaparin on steroid-related osteonecrosis, we used male New Zealand white rabbits. Osteonecrosis was induced by methylprednisolone-injection (1 * 20 mg/kg body weight). Control animals were treated with phosphate-buffered saline. Treatment consisted of an injection of 11.7 mg/kg body weight of enoxaparin per day (Clexane) in addition to methylprednisolone. Four weeks after methylprednisolone injection the animals were sacrificed. Histology (hematoxylin-eosin and Ladewig staining) was performed, and empty lacunae and histological signs of osteonecrosis were quantified. Histomorphometry revealed a significant increase in empty lacunae and necrotic changed osteocytes in glucocorticoid-treated animals as compared with the glucocorticoid- and Clexane-treated animals and with the control group. No significant difference was detected between the glucocorticoid and Clexane group and the control group. This finding suggests that cotreatment with enoxaparin has the potential to prevent steroid-associated osteonecrosis. PMID- 25110732 TI - Value and vulnerability assessment of a historic tomb for conservation. AB - Monumental tombs reflect various social, cultural, architectural, religious, economic, and engineering features of a community. However, environmental weathering, natural disasters, poor maintenance, vandalism, and misuse unfortunately pose serious threats to these cultural assets. Historic monuments are often exposed to the highest risk due to their vulnerability. The Ottoman style Nisanci Hamza Pasa tomb located in Karacaahmet Cemetery, Istanbul, the largest and oldest public cemetery in Turkey, is a case in point. The tomb consisting of six granite columns and a brick dome supported by six arches was constructed in 1605. Cracks, material loss, and decay as a result of adverse environmental effects and past earthquakes are evident. Therefore, this paper analyses the overall value of the tomb with respect to its historical, communal, evidential, and aesthetic aspects. Using the finite element approach and data on the tomb's material properties, a structural analysis under the self-weight and a time history analysis based on the earthquake ground motion data recorded in Duzce, Turkey, in November 1999 were conducted to encourage the conservation of this tomb and similar cultural heritage assets all over the world. The damage observed in the structure is congruent with the analysis results. PMID- 25110731 TI - Laser welded versus resistance spot welded bone implants: analysis of the thermal increase and strength. AB - INTRODUCTION: The first aim of this "ex vivo split mouth" study was to compare the thermal elevation during the welding process of titanium bars to titanium implants inserted in pig jaws by a thermal camera and two thermocouples. The second aim was to compare the strength of the joints by a traction test with a dynamometer. MATERIALS AND METHODS: Six pigs' jaws were used and three implants were placed on each side of them for a total of 36 fixtures. Twelve bars were connected to the abutments (each bar on three implants) by using, on one side, laser welding and, on the other, resistance spot welding. Temperature variations were recorded by thermocouples and by thermal camera while the strength of the welded joint was analyzed by a traction test. RESULTS: For increasing temperature, means were 36.83 and 37.06, standard deviations 1.234 and 1.187, and P value 0.5763 (not significant). For traction test, means were 195.5 and 159.4, standard deviations 2.00 and 2.254, and P value 0.0001 (very significant). CONCLUSION: Laser welding was demonstrated to be able to connect titanium implant abutments without the risk of thermal increase into the bone and with good results in terms of mechanical strength. PMID- 25110733 TI - Arsenic modulates posttranslational S-nitrosylation and translational proteome in keratinocytes. AB - Arsenic is a class I human carcinogen (such as inducing skin cancer) by its prominent chemical interaction with protein thio (-SH) group. Therefore, arsenic may compromise protein S-nitrosylation by competing the -SH binding activity. In the present study, we aimed to understand the influence of arsenic on protein S nitrosylation and the following proteomic changes. By using primary human skin keratinocyte, we found that arsenic treatment decreased the level of protein S nitrosylation. This was coincident to the decent expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). By using LC-MS/MS, around twenty S-nitrosoproteins were detected in the biotin-switched eluent. With the interest that arsenic not only regulates posttranslational S nitrosylation but also separately affects protein's translation expression, we performed two-dimensional gel electrophoresis and found that 8 proteins were significantly decreased during arsenic treatment. Whether these decreased proteins are the consequence of protein S-nitrosylation will be further investigated. Taken together, these results provide a finding that arsenic can deplete the binding activity of NO and therefore reduce protein S-nitrosylation. PMID- 25110735 TI - Mathematical analysis of the effect of rotor geometry on cup anemometer response. AB - The calibration coefficients of two commercial anemometers equipped with different rotors were studied. The rotor cups had the same conical shape, while the size and distance to the rotation axis varied. The analysis was based on the 2-cup positions analytical model, derived using perturbation methods to include second-order effects such as pressure distribution along the rotating cups and friction. The comparison with the experimental data indicates a nonuniform distribution of aerodynamic forces on the rotating cups, with higher forces closer to the rotating axis. The 2-cup analytical model is proven to be accurate enough to study the effect of complex forces on cup anemometer performance. PMID- 25110734 TI - PEEK cages versus PMMA spacers in anterior cervical discectomy: comparison of fusion, subsidence, sagittal alignment, and clinical outcome with a minimum 1 year follow-up. AB - PURPOSE: To compare radiographic and clinical outcomes after anterior cervical discectomy in patients with cervical degenerative disc disease using PEEK cages or PMMA spacers with a minimum 1-year follow-up. METHODS: Anterior cervical discectomy was performed in 107 patients in one or two levels using empty PEEK cages (51 levels), Sulcem PMMA spacers (49 levels) or Palacos PMMA spacers (41 levels) between January, 2005 and February, 2009. Bony fusion, subsidence, and sagittal alignment were retrospectively assessed in CT scans and radiographs at follow-up. Clinical outcome was measured using the VAS, NDI, and SF-36. RESULTS: Bony fusion was assessed in 65% (PEEK cage), 57% (Sulcem), and 46% (Palacos) after a mean follow-up of 2.5 years. Mean subsidence was 2.3-2.6 mm without significant differences between the groups. The most pronounced loss of lordosis was found in PEEK cages (-4.1 degrees ). VAS was 3.1 (PEEK cage), 3.6 (Sulcem), and 2.7 (Palacos) without significant differences. Functional outcome in the PEEK cage and Palacos group was superior to the Sulcem group. CONCLUSIONS: The substitute groups showed differing fusion rates. Clinical outcome, however, appears to be generally not correlated with fusion status or subsidence. We could not specify a superior disc substitute for anterior cervical discectomy. This trial is registered with DRKS00003591. PMID- 25110736 TI - A hop count based heuristic routing protocol for mobile delay tolerant networks. AB - Routing in delay tolerant networks (DTNs) is a challenge since it must handle network partitioning, long delays, and dynamic topology. Meanwhile, routing protocols of the traditional mobile ad hoc networks (MANETs) cannot work well due to the failure of its assumption that most network connections are available. In this paper, we propose a hop count based heuristic routing protocol by utilizing the information carried by the peripatetic packets in the network. A heuristic function is defined to help in making the routing decision. We formally define a custom operation for square matrices so as to transform the heuristic value calculation into matrix manipulation. Finally, the performance of our proposed algorithm is evaluated by the simulation results, which show the advantage of such self-adaptive routing protocol in the diverse circumstance of DTNs. PMID- 25110737 TI - Constructing topic models of Internet of Things for information processing. AB - Internet of Things (IoT) is regarded as a remarkable development of the modern information technology. There is abundant digital products data on the IoT, linking with multiple types of objects/entities. Those associated entities carry rich information and usually in the form of query records. Therefore, constructing high quality topic hierarchies that can capture the term distribution of each product record enables us to better understand users' search intent and benefits tasks such as taxonomy construction, recommendation systems, and other communications solutions for the future IoT. In this paper, we propose a novel record entity topic model (RETM) for IoT environment that is associated with a set of entities and records and a Gibbs sampling-based algorithm is proposed to learn the model. We conduct extensive experiments on real-world datasets and compare our approach with existing methods to demonstrate the advantage of our approach. PMID- 25110738 TI - A spread willingness computing-based information dissemination model. AB - This paper constructs a kind of spread willingness computing based on information dissemination model for social network. The model takes into account the impact of node degree and dissemination mechanism, combined with the complex network theory and dynamics of infectious diseases, and further establishes the dynamical evolution equations. Equations characterize the evolutionary relationship between different types of nodes with time. The spread willingness computing contains three factors which have impact on user's spread behavior: strength of the relationship between the nodes, views identity, and frequency of contact. Simulation results show that different degrees of nodes show the same trend in the network, and even if the degree of node is very small, there is likelihood of a large area of information dissemination. The weaker the relationship between nodes, the higher probability of views selection and the higher the frequency of contact with information so that information spreads rapidly and leads to a wide range of dissemination. As the dissemination probability and immune probability change, the speed of information dissemination is also changing accordingly. The studies meet social networking features and can help to master the behavior of users and understand and analyze characteristics of information dissemination in social network. PMID- 25110739 TI - A review of norms and normative multiagent systems. AB - Norms and normative multiagent systems have become the subjects of interest for many researchers. Such interest is caused by the need for agents to exploit the norms in enhancing their performance in a community. The term norm is used to characterize the behaviours of community members. The concept of normative multiagent systems is used to facilitate collaboration and coordination among social groups of agents. Many researches have been conducted on norms that investigate the fundamental concepts, definitions, classification, and types of norms and normative multiagent systems including normative architectures and normative processes. However, very few researches have been found to comprehensively study and analyze the literature in advancing the current state of norms and normative multiagent systems. Consequently, this paper attempts to present the current state of research on norms and normative multiagent systems and propose a norm's life cycle model based on the review of the literature. Subsequently, this paper highlights the significant areas for future work. PMID- 25110740 TI - Matrix transformations between certain sequence spaces over the non-Newtonian complex field. AB - In some cases, the most general linear operator between two sequence spaces is given by an infinite matrix. So the theory of matrix transformations has always been of great interest in the study of sequence spaces. In the present paper, we introduce the matrix transformations in sequence spaces over the field C(*) and characterize some classes of infinite matrices with respect to the non-Newtonian calculus. Also we give the necessary and sufficient conditions on an infinite matrix transforming one of the classical sets over C(*) to another one. Furthermore, the concept for sequence-to-sequence and series-to-series methods of summability is given with some illustrated examples. PMID- 25110741 TI - Multispectral image compression based on DSC combined with CCSDS-IDC. AB - Remote sensing multispectral image compression encoder requires low complexity, high robust, and high performance because it usually works on the satellite where the resources, such as power, memory, and processing capacity, are limited. For multispectral images, the compression algorithms based on 3D transform (like 3D DWT, 3D DCT) are too complex to be implemented in space mission. In this paper, we proposed a compression algorithm based on distributed source coding (DSC) combined with image data compression (IDC) approach recommended by CCSDS for multispectral images, which has low complexity, high robust, and high performance. First, each band is sparsely represented by DWT to obtain wavelet coefficients. Then, the wavelet coefficients are encoded by bit plane encoder (BPE). Finally, the BPE is merged to the DSC strategy of Slepian-Wolf (SW) based on QC-LDPC by deep coupling way to remove the residual redundancy between the adjacent bands. A series of multispectral images is used to test our algorithm. Experimental results show that the proposed DSC combined with the CCSDS-IDC (DSC CCSDS)-based algorithm has better compression performance than the traditional compression approaches. PMID- 25110742 TI - Recent advances in information technology. PMID- 25110743 TI - A rhythm-based authentication scheme for smart media devices. AB - In recent years, ubiquitous computing has been rapidly emerged in our lives and extensive studies have been conducted in a variety of areas related to smart devices, such as tablets, smartphones, smart TVs, smart refrigerators, and smart media devices, as a measure for realizing the ubiquitous computing. In particular, smartphones have significantly evolved from the traditional feature phones. Increasingly higher-end smartphone models that can perform a range of functions are now available. Smart devices have become widely popular since they provide high efficiency and great convenience for not only private daily activities but also business endeavors. Rapid advancements have been achieved in smart device technologies to improve the end users' convenience. Consequently, many people increasingly rely on smart devices to store their valuable and important data. With this increasing dependence, an important aspect that must be addressed is security issues. Leaking of private information or sensitive business data due to loss or theft of smart devices could result in exorbitant damage. To mitigate these security threats, basic embedded locking features are provided in smart devices. However, these locking features are vulnerable. In this paper, an original security-locking scheme using a rhythm-based locking system (RLS) is proposed to overcome the existing security problems of smart devices. RLS is a user-authenticated system that addresses vulnerability issues in the existing locking features and provides secure confidentiality in addition to convenience. PMID- 25110744 TI - Predicting the use of public transportation: a case study from Putrajaya, Malaysia. AB - Putrajaya is a new federal administrative capital of Malaysia which has been set to achieve a 70% share of all travels by public transport in the city area. However, the current modal split between the public transport and private transport is 15:85. In order to understand travelers' willingness to use the public transport, a conceptual model has been developed to determine the factors that affect them to use the public transport instead of travelling in their own cars. Various variables such as service quality, environmental impact, attitude, and behavior intention were analyzed and tested using structural equation model (SEM). Results indicate that the service quality and attitude are found to have positive effects on the behavioral intention of taking the public transport. Other than this, this study also shows that the service quality and environmental impact have some positive influences on the attitude to using the public transport. However, environmental impact has no significant, positive, and direct effect on behavioral intention. The results of this study demonstrate that the model that was developed is useful in predicting the public transport and it could provide a more complete understanding of behavioral intention towards public transport use. PMID- 25110745 TI - Hybrid polylingual object model: an efficient and seamless integration of Java and native components on the Dalvik virtual machine. AB - JNI in the Android platform is often observed with low efficiency and high coding complexity. Although many researchers have investigated the JNI mechanism, few of them solve the efficiency and the complexity problems of JNI in the Android platform simultaneously. In this paper, a hybrid polylingual object (HPO) model is proposed to allow a CAR object being accessed as a Java object and as vice in the Dalvik virtual machine. It is an acceptable substitute for JNI to reuse the CAR-compliant components in Android applications in a seamless and efficient way. The metadata injection mechanism is designed to support the automatic mapping and reflection between CAR objects and Java objects. A prototype virtual machine, called HPO-Dalvik, is implemented by extending the Dalvik virtual machine to support the HPO model. Lifespan management, garbage collection, and data type transformation of HPO objects are also handled in the HPO-Dalvik virtual machine automatically. The experimental result shows that the HPO model outweighs the standard JNI in lower overhead on native side, better executing performance with no JNI bridging code being demanded. PMID- 25110746 TI - Utility-oriented placement of actuator nodes with a collaborative serving scheme for facilitated business and working environments. AB - Places to be served by cyber-physical systems (CPS) are usually distributed unevenly over the area. Thus, different areas usually have different importance and values of serving. In other words, serving power can be excessive or insufficient in practice. Therefore, actuator nodes (ANs) in CPS should be focused on serving around points of interest (POIs) with considerations of "service utility." In this paper, a utility-oriented AN placement framework with a collaborative serving scheme is proposed. Through spreading serving duties among correctly located ANs, deployment cost can be reduced, utility of ANs can be fully utilized, and the system longevity can be improved. The problem has been converted into a binary integer linear programming optimization problem. Service fading, 3D placements, multiscenario placements, and fault-tolerant placements have been modeled in the framework. An imitated example of a CPS deployment in a smart laboratory has been used for evaluations. PMID- 25110747 TI - Synchronization control for stochastic neural networks with mixed time-varying delays. AB - Synchronization control of stochastic neural networks with time-varying discrete and continuous delays has been investigated. A novel control scheme is proposed using the Lyapunov functional method and linear matrix inequality (LMI) approach. Sufficient conditions have been derived to ensure the global asymptotical mean square stability for the error system, and thus the drive system synchronizes with the response system. Also, the control gain matrix can be obtained. With these effective methods, synchronization can be achieved. Simulation results are presented to show the effectiveness of the theoretical results. PMID- 25110748 TI - QoS measurement of workflow-based web service compositions using Colored Petri net. AB - Workflow-based web service compositions (WB-WSCs) is one of the main composition categories in service oriented architecture (SOA). Eflow, polymorphic process model (PPM), and business process execution language (BPEL) are the main techniques of the category of WB-WSCs. Due to maturity of web services, measuring the quality of composite web services being developed by different techniques becomes one of the most important challenges in today's web environments. Business should try to provide good quality regarding the customers' requirements to a composed web service. Thus, quality of service (QoS) which refers to nonfunctional parameters is important to be measured since the quality degree of a certain web service composition could be achieved. This paper tried to find a deterministic analytical method for dependability and performance measurement using Colored Petri net (CPN) with explicit routing constructs and application of theory of probability. A computer tool called WSET was also developed for modeling and supporting QoS measurement through simulation. PMID- 25110750 TI - Design and implementation of hybrid CORDIC algorithm based on phase rotation estimation for NCO. AB - The numerical controlled oscillator has wide application in radar, digital receiver, and software radio system. Firstly, this paper introduces the traditional CORDIC algorithm. Then in order to improve computing speed and save resources, this paper proposes a kind of hybrid CORDIC algorithm based on phase rotation estimation applied in numerical controlled oscillator (NCO). Through estimating the direction of part phase rotation, the algorithm reduces part phase rotation and add-subtract unit, so that it decreases delay. Furthermore, the paper simulates and implements the numerical controlled oscillator by Quartus II software and Modelsim software. Finally, simulation results indicate that the improvement over traditional CORDIC algorithm is achieved in terms of ease of computation, resource utilization, and computing speed/delay while maintaining the precision. It is suitable for high speed and precision digital modulation and demodulation. PMID- 25110749 TI - acACS: improving the prediction accuracy of protein subcellular locations and protein classification by incorporating the average chemical shifts composition. AB - The chemical shift is sensitive to changes in the local environments and can report the structural changes. The structure information of a protein can be represented by the average chemical shifts (ACS) composition, which has been broadly applied for enhancing the prediction accuracy in protein subcellular locations and protein classification. However, different kinds of ACS composition can solve different problems. We established an online web server named acACS, which can convert secondary structure into average chemical shift and then compose the vector for representing a protein by using the algorithm of auto covariance. Our solution is easy to use and can meet the needs of users. PMID- 25110751 TI - Assessment of potential location of high arsenic contamination using fuzzy overlay and spatial anisotropy approach in iron mine surrounding area. AB - Fuzzy overlay approach on three raster maps including land slope, soil type, and distance to stream can be used to identify the most potential locations of high arsenic contamination in soils. Verification of high arsenic contamination was made by collection samples and analysis of arsenic content and interpolation surface by spatial anisotropic method. A total of 51 soil samples were collected at the potential contaminated location clarified by fuzzy overlay approach. At each location, soil samples were taken at the depth of 0.00-1.00 m from the surface ground level. Interpolation surface of the analysed arsenic content using spatial anisotropic would verify the potential arsenic contamination location obtained from fuzzy overlay outputs. Both outputs of the spatial surface anisotropic and the fuzzy overlay mapping were significantly spatially conformed. Three contaminated areas with arsenic concentrations of 7.19 +/- 2.86, 6.60 +/- 3.04, and 4.90 +/- 2.67 mg/kg exceeded the arsenic content of 3.9 mg/kg, the maximum concentration level (MCL) for agricultural soils as designated by Office of National Environment Board of Thailand. It is concluded that fuzzy overlay mapping could be employed for identification of potential contamination area with the verification by surface anisotropic approach including intensive sampling and analysis of the substances of interest. PMID- 25110752 TI - Prediction of maize single cross hybrids using the total effects of associated markers approach assessed by cross-validation and regional trials. AB - The present study aimed to predict the performance of maize hybrids and assess whether the total effects of associated markers (TEAM) method can correctly predict hybrids using cross-validation and regional trials. The training was performed in 7 locations of Southern Brazil during the 2010/11 harvest. The regional assays were conducted in 6 different South Brazilian locations during the 2011/12 harvest. In the training trial, 51 lines from different backgrounds were used to create 58 single cross hybrids. Seventy-nine microsatellite markers were used to genotype these 51 lines. In the cross-validation method the predictive accuracy ranged from 0.10 to 0.96, depending on the sample size. Furthermore, the accuracy was 0.30 when the values of hybrids that were not used in the training population (119) were predicted for the regional assays. Regarding selective loss, the TEAM method correctly predicted 50% of the hybrids selected in the regional assays. There was also loss in only 33% of cases; that is, only 33% of the materials predicted to be good in training trial were considered to be bad in regional assays. Our results show that the predictive validation of different crop conditions is possible, and the cross-validation results strikingly represented the field performance. PMID- 25110753 TI - A fast density-based clustering algorithm for real-time Internet of Things stream. AB - Data streams are continuously generated over time from Internet of Things (IoT) devices. The faster all of this data is analyzed, its hidden trends and patterns discovered, and new strategies created, the faster action can be taken, creating greater value for organizations. Density-based method is a prominent class in clustering data streams. It has the ability to detect arbitrary shape clusters, to handle outlier, and it does not need the number of clusters in advance. Therefore, density-based clustering algorithm is a proper choice for clustering IoT streams. Recently, several density-based algorithms have been proposed for clustering data streams. However, density-based clustering in limited time is still a challenging issue. In this paper, we propose a density-based clustering algorithm for IoT streams. The method has fast processing time to be applicable in real-time application of IoT devices. Experimental results show that the proposed approach obtains high quality results with low computation time on real and synthetic datasets. PMID- 25110755 TI - Multilayer perceptron for robust nonlinear interval regression analysis using genetic algorithms. AB - On the basis of fuzzy regression, computational models in intelligence such as neural networks have the capability to be applied to nonlinear interval regression analysis for dealing with uncertain and imprecise data. When training data are not contaminated by outliers, computational models perform well by including almost all given training data in the data interval. Nevertheless, since training data are often corrupted by outliers, robust learning algorithms employed to resist outliers for interval regression analysis have been an interesting area of research. Several approaches involving computational intelligence are effective for resisting outliers, but the required parameters for these approaches are related to whether the collected data contain outliers or not. Since it seems difficult to prespecify the degree of contamination beforehand, this paper uses multilayer perceptron to construct the robust nonlinear interval regression model using the genetic algorithm. Outliers beyond or beneath the data interval will impose slight effect on the determination of data interval. Simulation results demonstrate that the proposed method performs well for contaminated datasets. PMID- 25110754 TI - High association between human circulating microRNA-497 and acute myocardial infarction. AB - Recent papers have reported the fundamental roles of miR-497 in infarction which acute myocardial infarction (AMI) belongs to. However, the expression levels of miR-497 in AMI patients were unclear, especially the circulating miR-497 that was detectable in the human plasma. In this study, we focused on the expression levels of circulating miR-497 in AMI and the roles of plasma miR-497 as a promising biomarker for AMI. The plasma miR-497 levels were detected from 27 AMI patients and 31 healthy volunteers by qRT-PCR. The cTnI concentrations of these samples were also analyzed by ELISA. Results showed circulating miR-497 levels were upregulated in AMI patients at 4 h, 8 h, 12 h, and 24 h, by contrast to those in control. Interestingly, time courses of circulating miR-497 levels displayed similar trends to that of cTnI concentrations in AMI patients; further study revealed the high correlation between circulating miR-497 and cTnI concentrations (r = 0.573, P < 0.001). At last, the receiver operating characteristic (ROC) curve was performed and declared that there was a faithworthy sensitivity and specificity to identify the AMI patients by using circulating miR-497. In conclusion, circulating miR-497 might be a promising biomarker for AMI identification and there was high association between human miR 497 and acute myocardial infarction. PMID- 25110756 TI - Process design of a ball joint, considering caulking and pull-out strength. AB - A ball joint for an automobile steering system is a pivot component which is connected to knuckle and lower control arm. The manufacturing process for its caulking comprises spinning and deforming. In this study, the process was simulated by flexible multibody dynamics. The caulking was evaluated qualitatively through numerical analysis and inspecting a plastically deformed shape. The structural responses of a ball joint, namely, pull-out strength and stiffness, are commonly investigated in the development process. Thus, following the caulking analysis, the structural responses were considered. In addition, three design variables related to the manufacturing process were defined, and the effects of design variables with respect to pull-out strength, caulking depth, and maximum stress were obtained by introducing the DOE using an L9 orthogonal array. Finally, the optimum design maximizing the pull-out strength was suggested. For the final design, the caulking quality and the pull-out strength were investigated by making six samples and their tests. PMID- 25110758 TI - A new step, a new challenge, a new beginning. PMID- 25110757 TI - Developing Attention: Behavioral and Brain Mechanisms. AB - Brain networks underlying attention are present even during infancy and are critical for the developing ability of children to control their emotions and thoughts. For adults, individual differences in the efficiency of attentional networks have been related to neuromodulators and to genetic variations. We have examined the development of attentional networks and child temperament in a longitudinal study from infancy (7 months) to middle childhood (7 years). Early temperamental differences among infants, including smiling and laughter and vocal reactivity, are related to self-regulation abilities at 7 years. However, genetic variations related to adult executive attention, while present in childhood, are poor predictors of later control, in part because individual genetic variationmay have many small effects and in part because their influence occurs in interaction with caregiver behavior and other environmental influences. While brain areas involved in attention are present during infancy, their connectivity changes and leads to improvement in control of behavior. It is also possible to influence control mechanisms through training later in life. The relation between maturation and learning may allow advances in our understanding of human brain development. PMID- 25110759 TI - Ultrasound evaluation of mediastinal lymphadenopathy in patients with sarcoidosis. AB - AIM: Mediastinal lymphadenopathy is a typical feature of pulmonary sarcoidosis and an important parameter for diagnosis and follow-up. The present feasibility study is the first to elucidate the role of transthoracic mediastinal ultrasonography (US) for evaluation and staging of lymphadenopathy in patients with sarcoidosis. MATERIAL AND METHOD: Fifty patients with sarcoidosis were subjected to high-definition mediastinal US. The sonographic lymph node status was compared with the radiologic staging - the prevailing gold standard. RESULTS: Mediastinal regions and landmarks could reliably be assessed by ultrasound in 45/50 (90%) of sarcoidosis patients. Lymphadenopathy was sonographically documented in 29/50 (58%) of the patients (sensitivity 89%, specificity 76%, PPV 86%, NPV 81%, accuracy 84%). There was a marked concordance between US confirmation of lymphadenopathy and radiologic staging (k=0.67, p<0.001). CONCLUSIONS: Transthoracic US qualifies for the demonstration of the mediastinal regions and lymphadenopathy in patients with sarcoidosis. The procedure is facilitated by frequent and distinct mediastinal lymph node enlargement due to sarcoidosis. Prospective studies are required to find out whether mediastinal US adds value to conventional radiologic staging and provides a clinically advantage, particularly in the follow-up of patients with sarcoidosis. PMID- 25110760 TI - The effectiveness of power Doppler vocal fremitus imaging in the diagnosis of breast hamartoma. AB - OBJECTIVES: To evaluate the usefulness of power Doppler vocal fremitus (PDVF) breast sonography for differentiation of hamartomas from other breast (malign or benign) masses. MATERIAL AND METHODS: Two hundred and six breast masses in 180 women were evaluated. The breast lesions were scanned first by mammography (MG), then by ultrasonography (US) with PDVF imaging. Finally, biopsy was performed on lesions suspicious for malignancy (n=172). We used PDVF imaging to evaluate whether the Power acoustic Doppler artifact existed in all breast lesions. RESULTS: Pathology results of 172 biopsied lesions showed that 83 were malign and 89 masses were benign. Totally 39 breast hamartomas were diagnosed radiologically (n=25) or histopathologically (n=14). All hamartomas (n=39) produced the power acoustic Doppler artifact as the surrounding tissue at the same depth in PDVF imaging. On the other hand, none of the malign or benign lesions, apart from hamartomas, evidenced a similar vibrational artifact as the surrounding tissue at the same depth in the PDVF imaging. CONCLUSION: PDVF imaging during breast sonography is an invaluable technique in the identification of breast hamartomas from other benign or malign breast masses. PMID- 25110761 TI - The measurement of the prostatic resistive index is a reliable ultrasonographic tool to stratify symptoms of patients with benign prosthatic hyperplasia. AB - AIMS: To evaluate the correlation between lower urinary tract symptoms (LUTS) and the resistive index (RI) of the transitional (TZ) and peripheral zone (PZ) of the prostate and to assess the impact of alpha blocker (AB) treatment on RI changes. MATERIAL AND METHODS: TZ-RI and PZ-RI values of 60 patients with LUTS were calculated by using transrectal ultrasound (TRUS). Correlations between the severity of LUTS and RI values were established. Then, AB was given to moderately and severe symptomatic patients with LUTS. One month after AB usage, TRUS was applied to assess the impact of AB on the TZ-RI, PZ-RI and the international prostate symptom score (IPSS). RESULTS: Participants were divided into 3 groups as mild (n=14), moderate (n=25) and severe symptomatic (n=21) patients. Mean TZ RI and PZ-RI were statistically different between the three groups (p<0.01). TZ RI and PZ-RI were correlated with the severity of LUTS (r=0.757, p<0.01 and r=0.699, p<0.01 respectively). A decrease in symptom severity and RI values in moderate and severe symptomatic groups were significant after AB treatment. CONCLUSIONS: TZ-RI and PZ-RI values can reflect the severity of LUTS and the AB treatment decreases the TZ-RI and the PZ-RI. Measuring the RI of the prostate by TRUS can be a useful tool to stratify LUTS's severity. PMID- 25110762 TI - Musculoskeletal ultrasound guided manoeuvres - a security profile. AB - BACKGROUND: In daily rheumatology clinical practice, routine interventional musculoskeletal ultrasound (MSUS) guided maneuvers such as aspiration, intraarticular or periarticular drug injections require efficient cleaning and disinfection methods for both transducer and patient's skin. AIM: To study the efficacy of probe and skin disinfection measures after using simple protocols, to identify the prevalence of septic and other drug related side effects after MSUS guided interventions and to quantify the total procedure time. MATERIAL AND METHODS: Recruitment of consecutive patients with different joint/ periarticular MSUS guided interventions was made in 3 medical centers. Bacterial load was determined on the transducers footprint after dry cleaning with the removal of any gel trace and on patients' skin after rigorous skin disinfection with either Bethadine or alcohol 70 degrees and Bethadine. Non-sterile gel was used as an ultrasound transmission medium. The time spent for some of the invasive procedures was quantified. RESULTS: Nine hundred and ninety eight MSUS guided interventional maneuvers were performed in 945 patients with inflammatory and degenerative musculoskeletal pathologies. Staphylococcus epidermidis was identified in 13.33% cases of the skin bacterial load analysis and in 37.50% cases of the footprint analysis. In two patients pathogenetic germs were detected on the skin. No septic post-procedural complications were reported. In 0.6% of the cohort other side effects occurred: aseptic osteonecrosis, skin depigmentation at injection site and iatrogenic microcristaline reactions. The median time frame dedicated to the intervention was 6 minutes. CONCLUSION: Rigorous transducer dry cleaning and Bethadine / Bethadine and alcohol 70 degrees skin disinfection are efficacious methods. The risk for septic complications and other drug related side effects related to MSUS guided injections is very low in this context. A correct injection technique must accompany the previous requests. Rapid and safe interventional maneuvers reduce the risks and control the costs of the healthcare system. PMID- 25110763 TI - Percutaneous treatment of symptomatic non-parasitic hepatic cysts. Initial experience with single-session sclerotherapy with polidocanol. AB - AIMS: Hepatic cysts have a prevalence of 2.5-7% and most of them are asymptomatic. However, large cysts may cause complaints; in such cases an appropriate treatment is necessary (open surgery, laparoscopic deroofing, removal of cystic fluid and injection of a sclerosing agent. The aim of this study was to assess the efficacy and safety of a single session technique with polidocanol in the therapy of symptomatic non parasitic hepatic cysts. MATERIAL AND METHODS. The study included 13 patients with symptomatic liver cysts (range 4-10 cm). All patients underwent percutaneous aspiration of the liver cyst under ultrasound guidance followed by instillation of polidocanol (3%, 4-10 ml). The patients were followed up at 1, 3 and 12 months. The disappearance of the cyst or reduction in volume more than 90% was considered successful. If the fluid was accumulated at 1month the procedure was repeated. If after the second injection the fluid accumulation was more than 50% of the initial volume the case was considered a failure and a laparoscopic deroofing was performed. RESULTS: The procedure was successful in 10 patients, 9 after the first instillation and one after the second (76.9%). The mean initial volume of cysts was 228 ml, and the mean reduction in volume at 1, 3 and 12 months was 80.2%, 91.9% and 96.7%. The cyst resolution was gradual with clinically significant cyst reduction achievement within 1 year after therapy. In 3 patients the fluid reaccumulated at the same volume despite 2 instillations. Those 3 cases the procedure was considered failure and the patients were sent to surgery. In 2 patients (one successfully treated and one with treatment failure) bleeding during the first puncture and aspiration appeared and the therapy was postponed for 1 month. There were no significant adverse effects, and all the patients had relief of symptoms after therapy. CONCLUSIONS: This initial experience with percutaneous aspiration and polidocanol sclerosis of hepatic cysts demonstrated that the technique is efficient and safe. PMID- 25110764 TI - Real time sonoelastographic evaluation of renal allografts in correlation with clinical prognostic parameters: comparison of linear and convex transducers according to segmental anatomy. AB - BACKGROUND: Renal transplantation is the treatment of choice in end-stage renal disease. Chronic allograft dysfunction is the leading cause of chronic allograft failure. Surveillance biopsy is the only reliable tool to detect early fibrosis in the allograft. There is a need for non-invasive methods for the detection of early development of renal allograft fibrosis. AIMS: To analyze the reliability of sonographic elasticity index and resistive index measurements in the evaluation of renal transplant fibrosis using linear and convex transducers according to segmental anatomy. MATERIALS AND METHODS: Elasticity index and resistive index were measured in 28 renal transplants and correlated with clinical prognostic parameters. Donor age above 50 years old, post transplantation time over 60 months and serum creatinine level above 1.5 mg/dl were defined as poor prognostic parameters. RESULTS: Renal transplant recipients with serum creatinine level above 1.5 mg/dl demonstrated higher mean elasticity index (p=0.006) with a convex probe and higher elasticity index in the middle segments both with a convex and a matrix linear probe (p=0.026, p=0.001). Renal transplant recipients with post-transplantation time of 60 months and more demonstrated higher resistive index values in the middle segments (p=0.016). CONCLUSIONS: Convex probe was able to detect the changes in mean stiffness better than the matrix linear probe. The measurements from subsegments might suggest that diffuse changes in stiffness can truly be detected in the middle segments or that fibrotic processes start from the middle segments of the renal transplants. Further studies correlated with histopathology are required to validate the findings. PMID- 25110765 TI - Noninvasive assessment of liver steatosis using ultrasound methods. AB - Hepatic steatosis is a condition frequently encountered in clinical practice, with potential progression towards chirrhosis and hepatocellular carcinoma. Ultrasonography (US) is one of the noninvasive imaging techniques used in the diagnosis of steatosis. We will review the US diagnostic criteria, the US performance in the diagnosis and grading of hepatic steatosis, the US steatosis models, but also its limitations in the diagnosis of steatosis. In addition, we will discuss 2 modern methods of assessing hepatic steatosis using ultrasounds, namely the computerized processing of data forming the US image and the controlled attenuation parameter measured with unidimensional transient elastography. PMID- 25110766 TI - Ultrasound guided axillary brachial plexus block. AB - The axillary brachial plexus block is the most widely performed upper limb block. It is relatively simple to perform and one of the safest approaches to brachial plexus block. With the advent of ultrasound technology, there is a marked improvement in the success rate of the axillary block. This review will focus on the technique of ultrasound guided axillary brachial plexus block. PMID- 25110767 TI - How can the use of lung ultrasound in cardiac arrest make ultrasound a holistic discipline. The example of the SESAME-protocol. AB - The most critical application of critical ultrasound - cardiac arrest - is the opportunity for technical considerations. The necessity to immediately detect reversible causes is integrated in the concept of holistic ultrasound. Holistic ultrasound is defined as a discipline where each element interacts with the others, and where the understanding of each of them allows understanding the whole. A narrow machine (not necessarily a laptop), a fast start-on time, a simple keyboard highlighting three useful buttons, a universal microconvex probe able to immediately detect pneumothorax, then deep venous thrombosis, then abdominal bleeding, then pericardial tamponade, then cardiac anomalies will allow a fast protocol. The concept of holistic ultrasound is particularly on focus in the first step done at the lung (search for pneumothorax and clearance for fluid therapy), since the best image is obtained with the simplest equipment devoid of traditional facilities (image filtering, harmonics, time lag, Doppler...). The same simple gray-scale equipment is used for the other steps, all what is needed is to see the real-time image of what is facing the probe: the very principle of visual medicine. The same approach can be used with no change, just more quietly, for many less urgent settings. PMID- 25110768 TI - The role of ultrasound in the imaging assessment of the augmented breast. A pictorial review. AB - The imaging evaluation of the augmented breast is becoming more and more frequent in daily practice. Even if mammography remains the golden standard for breast cancer screening, ultrasound is used as a first step investigation in young symptomatic patients or as a screening tool in detecting pathology related to the implants. This pictorial essay reviews the indications and limitations of the imaging methods and illustrates the normal and pathological ultrasound findings in the augmented breast. PMID- 25110769 TI - Fournier's gangrene. Case report. AB - Fournier's gangrene is a condition marked by fulminant polymicrobial necrotizing fasciitis of the urogenital and perineal areas. We present a patient with Fournier's gangrene and describe the physical examination and bedside sonographic findings. These findings can assist in the evaluation of patients with concerning symptoms so there can be timely administration of antibiotics and specialist consultation when necessary. PMID- 25110770 TI - Bilateral subclavian steal syndrome in an intensive care unit. A case report. AB - We report the case of a 56-year-old man who presented with arterial hypotension, lightheadedness, vomiting, a sense of tingling in his right arm, and a right beating horizontal nystagmus. He was initially admitted to the Intensive care unit and treated with standard vasopressor agents. A neurosonological examination showed the steal phenomenon on both vertebral arteries; the neuroradiological examination revealed occlusion of the left subclavian artery and subtotal stenosis of the innominate artery. Percutaneous transluminal angioplasty was performed. Our case demonstrates how bilateral subclavian steal syndrome should be taken into account in the case of a seemingly hypotensive patient unresponsive to standard therapy. PMID- 25110771 TI - Cutaneous histiocytoma - histological and imaging correlations. A case report. AB - Dermatofibroma (benign fibrous histiocytoma) represents one of the most common skin tumors. We present the case of a 52 year old female patient with a highly pigmented nodular lesion, localized on the right thigh. Dermoscopy completed the clinical diagnosis, but could not exclude a malignant tumour . Ultrasound examination (Dermascan C sonograms 20 MHz, 2D ultrasound, Doppler ultrasound, contrast enhanced ultrasound, and elastography) evidenced a highly vascularized lesion (peripheral type of vascularization), and a sonographic depth index of 8.3 mm. The histopathological examination confirmed the diagnosis of a benign fibrous histiocytoma with the histological Breslow index of 8 mm. The particularity of the case consists of the complex non-invasive and in real time imaging examination which describes the "in vivo" histology of the benign tumor lesion. PMID- 25110772 TI - Contrast enhanced ultrasound of a hepatic soft tissue angiosarcoma metastasis. Case report. AB - Diagnostic imaging of angiosarcoma and angiosarcoma metastasis has been described as confusing and challenging. We present a rare case of hepatic soft tissue angiosarcoma metastasis, which was diagnosed by contrast enhanced ultrasound (CEUS). The case further exemplifies the ability of CEUS to solve discrepancies between other imaging modalities. PMID- 25110773 TI - Diagnosis of sacrococcygeal teratoma using two and three-dimensional ultrasonography: two cases reported and a literature review. AB - The occurrence of a fetal tumor is rare, 50% of all fetal tumors being sacrococcygeal teratomas. Prenatal diagnosis of this condition is important for the monitoring of the affected fetuses and for establishing the mode and time of delivery. We describe two cases of fetal sacrococcygeal teratoma diagnosed by 2D- and 3D-ultrasound. Three-dimensional ultrasound proved to be useful both in the diagnosis and patient counseling. The combination of 2D- and 3D-ultrasound enables the diagnosis to be made during the first trimester of pregnancy. PMID- 25110774 TI - Efficient enrichment of glycopeptides using metal-organic frameworks by hydrophilic interaction chromatography. AB - Selective enrichment of glycopeptides from complicated biological samples is critical for glycoproteomics to obtain the structure and glycosylation information of glycoproteins using mass spectrometry (MS), which still remains a great challenge. Hydrophilic interaction chromatography (HILIC)-based strategies have been proposed for selective isolation of glycopeptides via the interactions between the glycan of glycopeptides and the matrices. However, the application of these methods is limited by the medium selectivity of HILIC matrices. In this study, hydrophilic metal-organic frameworks (MOFs) were fabricated and used as a HILIC matrix. The cross-linked CD-MOFs (LCD-MOFs) were facilely prepared with gamma-cyclodextrin as ligand and possessed nano-sized cubic structure, superior hydrophilicity, and bio-compatibility. The LCD-MOFs performance for the selective enrichment of glycopeptides from the complex biological samples were investigated with a digested mixture of human immunoglobulin G (IgG) that was used as standard samples. In the selectivity assessment, the non-glycopeptides causing ion suppression to the glycopeptides were effectively removed, the signal of glycopeptides were enhanced significantly by LCD-MOFs, and twenty glycopeptides were identified with 67 fmol of IgG digest. In addition, the resulting LCD-MOFs demonstrated the lower detection limit (3.3 fmol) with a satisfactory recovery yield (84-103%) for glycopeptide enrichment from a digest of IgG. Furthermore, a promising protocol was developed for the selective enrichment of glycopeptides from mouse liver, and 344 unique N-glycosylation sites that mapped to 290 different glycoproteins were identified in a single MS run. The results clearly demonstrated that when used in a HILIC matrix, LCD-MOFs have great potential for identifying and enriching low-abundant glycopeptides in complex biological samples. PMID- 25110775 TI - Reply: To PMID 24762147. PMID- 25110776 TI - Assessment of the effect of the climate variations of coastal surface water and study of Sepia officinalis spawing. AB - The aim of this study was to establish whether climate change affected migratory behaviour of Sepia officinalis (Linnaeus, 1758), which is an important resource for small-scale fishermen of Abruzzo region (Italy). Starting at the beginning of March until the end of April, the cuttlefish in this area migrates from deep cold water towards warmer coastal waters, where they spawn. Small-scale fishing of cuttlefish is permitted in costal waters from March to September. During the study period, between March and September 2008, both cuttlefish traps and trammel nets were used in 5 sampling areas along the Abruzzo coast to test their relative efficiency in catching cuttlefish. Trapped specimens were counted, weighed and measured, their gender and sexual maturity were also determined. The data obtained from the sampling were correlated to surface water temperature to assess possible changes in migration behaviours. The obtained data show that during the first months of migration (March and April), a greater percentage of large males was caught, while females and smaller males predominated later in the year. The study also showed that surface water temperature did not reveal any significant shifts from the trend over the last 10 years. As for the efficiency of the fishing methods, traps were found to be more effective than trammel nets. PMID- 25110777 TI - Collaboration through competition. PMID- 25110778 TI - The author file: Andrew Straw. PMID- 25110779 TI - Points of significance: Analysis of variance and blocking. PMID- 25110780 TI - The human proteome takes the spotlight. PMID- 25110781 TI - Visualizing voltage. PMID- 25110782 TI - More specific CRISPR editing. PMID- 25110783 TI - Cancer stem cells on demand. PMID- 25110784 TI - The sobering reality of outcomes when older adults require prolonged mechanical ventilation. PMID- 25110785 TI - Author response. PMID- 25110786 TI - Author response. PMID- 25110787 TI - Letter to the editor: resident presentations at scientific meetings. PMID- 25110788 TI - Embodiment without bodies? Analysis of embodiment in US-based pro-breastfeeding and anti-male circumcision movements. AB - This article uses the cases of pro-breastfeeding and anti-circumcision activism to complicate the prevailing conceptualisation of embodiment in research on embodied health movements (EHMs). Whereas most EHM activists draw on their own bodily experiences, in the breastfeeding and circumcision movements, embodiment by proxy is common. Activists use embodiment as a strategy but draw on physical sensations that they imagine for other people's bodies, rather than on those they experience themselves. Pro-breastfeeding activists, who seldom disclose whether they were themselves breastfed, target mothers, encouraging them to breastfeed rather than to formula feed their children in order to reduce their child's risk of disease. Anti-circumcision activists, only some of whom are circumcised men, urge parents to leave their sons' penises intact in order to avoid illness and disfigurement and to preserve the sons' rights to make their own informed decisions as adults. In both movements activists use embodiment as a persuasive strategy even though they themselves do not necessarily embody the risks of the negative health outcomes with which they are concerned. Future research on EHMs should reconceptualise EHMs to include embodiment by proxy and examine whether this important phenomenon systematically affects movement strategies and outcomes. PMID- 25110789 TI - Careful science? Bodywork and care practices in randomised clinical trials. AB - Concern about obesity has prompted numerous public health campaigns that urge people to be more physically active. The campaigns often include normative statements and attempt to impose restrictions on individuals' lives without considering the complexities of daily life. We suggest that broadening the focus to reflect everyday practices would foster better targeted public health campaigns. This article is based on our participation in FINE, a multidisciplinary Danish research project. The core methodology of FINE was a randomised controlled trial in which 61 moderately overweight men were put into different exercise groups. In this article we analyse the scientific work of the trial as representing entangled processes of bodywork, where data are extracted and objectified bodies are manipulated and care practices address the emotional, social and mundane aspects of the participants' everyday lives. Care practices are an inherent part of producing scientific facts but they are removed from the recognised results of scientific practice and thus from common public health recommendations. However, knowledge about the strategic use of care practices in lifestyle interventions is important for public health initiatives and future efforts should incorporate this aspect. PMID- 25110790 TI - Constructing notions of healthcare productivity: the call for a new professionalism? AB - Improving performance is an imperative for most healthcare systems in industrialised countries. This article considers one such system, the UK's National Health Service (NHS). Recent NHS reforms and strategies have advocated improved healthcare productivity as a fundamental objective of policy and professional work. This article explores the construction of productivity in contemporary NHS discourse, analysing it via the Foucauldian concept of governmentality. In this manner it is possible to investigate claims that the commodification of health work constitutes a threat to autonomy, and counter that with an alternative view from a perspective of neoliberal self-governance. Contemporary policy documents pertaining to NHS productivity were analysed using discourse analysis to examine the way in which productivity was framed and how responsibility for inefficient resource use, and possible solutions, were constructed. Data reveals the notion of productivity as problematic, with professionals as key protagonists. A common narrative identifies traditional NHS command/control principles as having failed to engage professionals or having been actively obstructed by them. In contrast, new productivity narratives are framed as direct appeals to professionalism. These new narratives do not support deprofessionalisation, but rather reconstruct responsibilities, what might be called 'new professionalism', in which productivity is identified as an individualised professional duty. PMID- 25110791 TI - Response to McDermott. PMID- 25110792 TI - Response to Hiatt et al. PMID- 25110793 TI - Buccal mucosal graft in reconstructive urology: uses beyond urethral stricture. AB - The use of buccal mucosal grafts for the reconstruction of urethral strictures is an established procedure. Because of its robustness, the buccal mucosal graft could also potentially provide an alternative for other indications in reconstructive urology. We report here six consecutive patients who received a buccal mucosal graft for ureteral strictures, glans reconstruction and stoma stenosis. The follow up for all patients ranged from 26 to 50 months. The buccal mucosal graft showed excellent functional results for the ureteral strictures and stenosis from ureterocutaneostomy. For glans reconstructions, the buccal mucosal grafts delivered excellent cosmetic and functional results without causing meatal stenosis. We conclude the buccal mucosal graft can be used in reconstructive surgery beyond the reconstruction of urethral strictures. PMID- 25110794 TI - Editorial comment to buccal mucosal graft in reconstructive urology: uses beyond urethral stricture. PMID- 25110795 TI - Stent-assisted coil embolization--response. PMID- 25110796 TI - Lamina terminalis fenestration--response. PMID- 25110797 TI - Internal carotid artery anterior wall aneurysms--response. PMID- 25110798 TI - The health of healthcare, Part V: Is the very freedom of providers at risk? AB - When healthcare is fully compliant with the Patient Protection and Affordable Health Care Act, U.S. health care providers lose their one inalienable American right, namely freedom, and can no longer fulfill their fiduciary responsibility to patients. PMID- 25110799 TI - Eating small: applications and implications for nano-technology in agriculture and the food industry. PMID- 25110800 TI - Oncology medical home study examines physician payment models. PMID- 25110801 TI - Utility of genetic testing linked to clinical interpretation. PMID- 25110802 TI - Gum chewing: is it helpful or harmful? PMID- 25110804 TI - Mercury ion responsive wettability and oil/water separation. AB - A novel Hg(2+) responsive oil/water separation mesh with poly(acrylic acid) hydrogel coating is reported. The mesh can separate oil and water because of the superhydrophilicity of the poly(acrylic acid) hydrogel coating on the mesh, and switch the wettability based on the chelation between Hg(2+) and poly(acrylic acid) . The reversible change in oil contact angle of as-prepared mesh is about 149 degrees after immersion in Hg(2+) solution. This mesh is an ideal candidate for oil-polluted water purification, especially for water that contains Hg(2+) contaminant. PMID- 25110805 TI - Increased serum heme oxygenase-1 levels as a diagnostic marker of oxidative stress in preeclampsia. AB - OBJECTIVE: To evaluate the utility of serum biomarkers in the diagnosis of preeclampsia (PE) and also investigate possible correlation with pathogenesis of PE. METHODS: Maternal serum concentrations of heme oxygenase-1 (HO1) and N-myc downstream-regulated gene 1 (NDRG1) were measured at 27-34 weeks of gestation in a case-control study of 33 pregnant women diagnosed with PE and in 43 normotensive pregnant women without proteinuria. The Mann-Whitney U test and Spearman's correlation were used for statistical analysis. RESULTS: The median serum HO1 level was found to be significantly higher in the PE group [76.7 ng/ml (23.4-445.7)] than control group [55.9 ng/ml (3.7-354.3)] (p = 0.006). Positive correlation was found between HO1 levels with presence of PE (r = 0.316, p = 0.005). There was no significant difference in NDRG1 values between the two groups (p = 0.226). CONCLUSIONS: Serum HO1 levels were found to be increased in patients with PE compared with normotensive pregnant women. PMID- 25110806 TI - Synthesis and fungistatic activity of bicyclic lactones and lactams against Botrytis cinerea, Penicillium citrinum, and Aspergillus glaucus. AB - Six analogues of natural trans-4-butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and three derivatives, 11, 12, and 13, of Vince lactam (10) were synthesized and tested as fungistatic agents against Botrytis cinerea AM235, Penicillium citrinum AM354, and six strains of Aspergillus. Moreover, bioresolution carried out by means of whole cell microorganisms and commercially available enzymes afforded opposite enantiomerically enriched (-) and (+) isomers of Vince lactam (10), respectively. The effect of compound structures and stereogenic centers on biological activity has been discussed. The highest fungistatic activity was observed for four lactones: 3, 4, 7, and 8 (IC50 = 104.6-115.2 MUg/mL) toward B. cinerea AM235. cis-5,6-Epoxy-2-aza[2.2.1]heptan-3-one (13) indicated significant fungistatic activity (IC50 = 107.1 MUg/mL) against Aspergillus glaucus AM211. trans-4-Butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and trans-4-butyl-cis-3 oxabicyclo[4.3.0]non-7-en-2-one (7) exhibited high fungistatic activity (IC50 = 143.2 and 110.2 MUg/mL, respectively) against P. citrinum AM354 as well. PMID- 25110807 TI - Pulsed magnetic field induced fast drug release from magneto liposomes via ultrasound generation. AB - Fast drug delivery is very important to utilize drug molecules that are short lived under physiological conditions. Techniques that can release model molecules under physiological conditions could play an important role to discover the pharmacokinetics of short-lived substances in the body. Here an experimental method is developed for the fast release of the liposomes' payload without a significant increase in (local) temperatures. This goal is achieved by using short magnetic pulses to disrupt the lipid bilayer of liposomes loaded with magnetic nanoparticles. The drug release has been tested by two independent assays. The first assay relies on the AC impedance measurements of MgSO4 released from the magnetic liposomes. The second standard release assay is based on the increase of the fluorescence signal from 5(6)-carboxyfluorescein dye when the dye is released from the magneto liposomes. The efficiency of drug release ranges from a few percent to up to 40% in the case of the MgSO4. The experiments also indicate that the magnetic nanoparticles generate ultrasound, which is assumed to have a role in the release of the model drugs from the magneto liposomes. PMID- 25110808 TI - Effect of astaxanthin on cataract formation induced by glucocorticoids in the chick embryo. AB - PURPOSE: To examine whether astaxanthin (AST) prevent the cataract formation induced by glucocorticoid in chick embryo. MATERIALS AND METHODS: Hydrocortisone hemisuccinate sodium (HC) (0.5 MUmol/egg) was administered directly into the air chamber in the egg shell of chick embryo day 15. The eggs were then kept in an incubator at same conditions and administered 100 MUL of 50 (HC + AST50 group), 80 (HC + AST80 group), 100 (HC + AST100 group) mg/mL of AST solutions dissolved in dimethyl sulfoxide (DMSO) 3 h after administration of HC. In addition, non-HC treated group (treated with physiological saline without HC and 100 MUL of DMSO), HC-alone group (treated with 0.5 MUmol of HC and 100 MUL of DMSO), and AST100 group (treated with physiological saline without HC and 100 MUL of DMSO) were also incorporated. After 48 h of treatment, lenses were removed from embryo and classified into five stages according to developed opacity. The amounts of reduced glutathione in the lenses and the blood glucose levels were measured. RESULTS: The average scores of lens opacitiy were 2.63 +/- 1.02 nmol/lens (HC alone), 2.78 +/- 0.97 nmol/lens (HC + AST50), 2.22 +/- 1.20 nmol/lens (HC + AST80) and 1.84 +/- 0.83 nmol/lens (HC + AST100; p < 0.05), respectively. Administration of AST decreased the lens opacity dose-dependently. The amounts of reduced glutathione in lenses were 11.6 +/- 2.8 nmol/lens (HC-alone), 11.3 +/- 2.7 nmol/lens (HC + AST50), 13.4 +/- 2.4 nmol/lens (HC + AST80) and 13.7 +/- 3.1 nmol/lens (HC + AST100; p < 0.05), respectively. Higher levels of AST prevented loss of reduced glutathione from the lens. CONCLUSION: These findings support that AST protects glucocorticoid-induced cataract in chick embryo. PMID- 25110809 TI - Efficacy of carbonaceous materials for sorbing polychlorinated biphenyls from aqueous solution. AB - Interest in incorporating nanomaterials into water treatment technologies is steadily growing, driving the necessity to understand the interaction of these new materials with specific water contaminants. In the present study, five different carbonaceous materials: activated carbon (AC), charcoal (BC), carbon nanotubes (CNT), graphene (GE), and graphene oxide (GO) were investigated as sorbent materials for 11 polychlorinated biphenyl (PCB) congeners in aqueous concentrations in the pg-MUg/L range. Sorbent-water distribution coefficients (Ks) calculated in aqueous concentrations of ng/L show that AC is superior to GE, GO, CNT, and BC for the 11 PCB congeners investigated by an average of 1.1, 1.1, 1.3, and 2.5 orders of magnitude, respectively. Additionally, maximum capacity and sorption affinity parameters from the Langmuir, Freundlich, and Polanyi Dubinin-Manes (PDM) models show a similar result. Interestingly, however, the effect of molecular planarity has greater impact on PCB sorption to the nanomaterials, such that the planar congeners form stronger bonds with CNT, GE, and GO compared to AC and BC. This work demonstrated superior PCB sorption by AC as compared with the nanomaterials examined such that substantial post production modifications would be necessary for the nanomaterials to out-perform AC. PMID- 25110810 TI - Component-controllable WS(2(1-x))Se(2x) nanotubes for efficient hydrogen evolution reaction. AB - Owing to the excellent potential for fundamental research and technical applications in optoelectronic devices and catalytic activity for hydrogen evolution reaction (HER), transition metal dichalcogenides have recently attracted much attention. Transition metal sulfide nanostructures have been reported and demonstrated promising application in transistors and photodetectors. However, the growth of transition metal selenide nanostructures and their applications has still been a challenge. In this work, we successfully synthesized high-quality WSe2 nanotubes on carbon fibers via selenization. More importantly, through optimizing the growth conditions, ternary WS2(1-x)Se2x nanotubes were synthesized and the composition of S and Se can be systematically controlled. The as-grown WS2(1-x)Se2x nanotubes on carbon fibers, assembled as a working electrode, revealing low overpotential, high exchange current density, and small series resistance, exhibit excellent electrocatalytic properties for hydrogen evolution reaction. Our study provides the experimental groundwork for the synthesis of low-dimensional transition metal dichalcogenides and may open up exciting opportunities for their application in electronics, photoelectronics, and catalytic electrochemical reactions. PMID- 25110811 TI - Stability of the cationic oxidation states in Pr(0.50)Sr(0.50)CoO3 across the magnetostructural transition by X-ray absorption spectroscopy. AB - The possible hybridization between Pr 4f and O 2p states in Pr(0.50)Sr(0.50)CoO3 at low temperatures was investigated by different techniques. First, using neutron diffraction we observed a strong contraction of some Pr-O bonds across the magnetostructural transition at T(S) ~ 120 K. In contrast to the Pr-O bond contraction in Pr(0.50)Sr(0.50)CoO3, this transition is not accompanied by the appearance of Pr(4+) at low temperatures, as revealed by X-ray absorption spectroscopy at Pr edges. Despite the fact that a Pr valence change is not the mechanism that drives this transition, we point out an active participation of Pr ions across T(S). Moreover, Co L(2,3)-edge and O K edge X-ray absorption spectra did not reveal any spin-state variation and showed the stability of the average formal valence of cobalt ions. The large density of empty t(2g) symmetry states in the studied thermal range does not suggest the occurrence of Co(3+) in a pure low-spin state. The overall metallic behavior agrees with our findings. We propose a mixture of Co(3+) ions in the intermediate-spin or high-spin configuration together with Co(4+) ions in a low- or intermediate-spin state. PMID- 25110812 TI - A novel method to identify fat malabsorption: the Serum Retinyl Palmitate Test. AB - BACKGROUND: Malabsorptive etiologies of chronic diarrhea are important to identify. The 72-h stool for fecal fat test (FFT), the gold standard for diagnosing fat malabsorption, is fraught with limitations that impact its reliability. Vitamin A, a fat-soluble vitamin, parallels the absorption of lipids. We assessed the feasibility and validate a novel clinical test, retinyl palmitate (RP), for the diagnosis of fat malabsorption, and to compare the results to the FFT. METHODS: Using a case-control study design, patients with chronic diarrhea secondary to suspected malabsorption, and healthy control subjects were identified. A Dietitian taught subjects to consume a 100g fat diet for the FFT with measurements of stool fat after 72-h. Serum levels of Vitamin A (retinol) and RP were measured by reversed-phase high pressure liquid chomatography. Two-way comparisons were made between the groups using 2 sample Wilcoxon rank-sum tests. RESULTS: Sixteen patients completed this study (8 cases and 8 control subjects). Fecal fat results were available for 15/16 patients. The sensitivity of the FFT was 100% (identified all cases), but the FFT specificity was 42%, as 4/7 control patients were identified as malabsorbers. Cases with short bowel syndrome had the lowest RP levels but this did not meet statistical significance. There was no significant difference for serum RP levels when comparing cases and control patients' AUC. CONCLUSIONS: Serum RP is useful to identify malabsorption, albeit in severe cases. Furthermore, we have shown that the 72-hour FFT has poor performance characteristics, highlighting the need for more useful diagnostics in identifying malabsorption. PMID- 25110813 TI - Performance enhancement in the measurement of 5 endogenous steroids by LC-MS/MS combined with differential ion mobility spectrometry. AB - BACKGROUND: Challenges for steroid analysis by LC-MS/MS include low ionization efficiency, endogenous isobars with similar fragmentation patterns and chromatographic retention. Differential ion mobility spectrometry (DMS) provides an additional degree of separation prior to MS/MS detection, and shows promise in improving specificity of analysis. We developed a sensitive and specific method for measurement of corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, 17 hydroxyprogesterone and progesterone in human serum and plasma using an ABSciex 5500 mass spectrometer equipped with a differential ion mobility interface. METHODS: 250MUL aliquots of serum were spiked with deuterated internal standards and extracted with MTBE. The samples were analyzed using positive mode electrospray LC-DMS-MS/MS. The method was validated and compared with immunoassays and LC-MS/MS methods of reference laboratories. RESULTS: Inter and intra assay imprecision was <10%. Limits of quantification and detection in nmol/L were 0.18, 0.09 for corticosterone and 17-hydroxyprogesterone, 0.30, 0.16 for 11-deoxycortisol, 0.12, 0.06 for progesterone and 0.06, 0.03 for 11 deoxycorticosterone. Comparison for progesterone and 17-hydroxyprogesterone with immunoassay showed slopes of 0.97 and 1.0, intercepts of 0.16 and 0.10 and coefficients of determination (r(2)) of 0.92 and 0.97, respectively. Progesterone by immunoassay showed positive bias in samples measuring <3.18nmol/L. Reference intervals for progesterone and 11-deoxycorticosterone in post-menopausal women were found to be <2.88 and <0.28nmol/L respectively. CONCLUSIONS: We developed and validated an LC-DMS-MS/MS method for analysis of five endogenous steroids suitable for routine measurements in clinical diagnostic laboratories. Specificity gained with DMS allows reducing the complexity of sample preparation, decreasing LC run times and increasing speed of the analysis. PMID- 25110814 TI - Application of nuclear magnetic resonance spectroscopy for identification of ciprofloxacin crystalluria. AB - This is a report describing a previously healthy young patient, who experienced crystalluria and non-cholestatic acute liver injury after a single intravenous dose of 400mg. The nuclear magnetic resonance spectra confirmed that the urinary sediment in our patient was formed by pure ciprofloxacin. The nuclear magnetic resonance spectra ((1)H NMR) of the urine sediment are a good test to confirm the composition of the crystals observed by electron microscopy and infrared spectrum. The findings indicate the importance of adequate hydration, urinalysis, measurement of pH and liver enzyme levels, prior to treatment with ciprofloxacin. Our findings also indicate that ciprofloxacin should not be administered to patients with renal tubular acidosis, due to their high urinary pH. PMID- 25110815 TI - Assessment of the reproducibility of oligoclonal IgM band detection for its application in daily clinical practice. AB - BACKGROUND: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice. METHODS: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre. RESULTS: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71. CONCLUSION: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting. PMID- 25110816 TI - Spontaneous neural activity alterations in temporomandibular disorders: a cross sectional and longitudinal resting-state functional magnetic resonance imaging study. AB - The involvement of the central nervous system in the pathophysiology of temporomandibular disorders (TMD) has been noticed. TMD patients have been shown dysfunction of motor performance and reduced cognitive ability in neuropsychological tests. The aim of this study is to explore the spontaneous neural activity in TMD patients with centric relation (CR)-maximum intercuspation (MI) discrepancy before and after stabilization splint treatment. Twenty-three patients and twenty controls underwent clinical evaluations, including CR-MI discrepancy, Helkimo indices and chronic pain, and resting state functional magnetic resonance imaging scans at baseline. Eleven patients repeated the evaluations and scanning after the initial wearing (T1) and 3months of wearing (T2) of the stabilization splint. The fractional amplitude of low-frequency fluctuation (fALFF) was calculated to compare the neural functions. At baseline, the patients showed decreased fALFF in the left precentral gyrus, supplementary motor area, middle frontal gyrus and right orbitofrontal cortex compared with the controls (P<0.05, AlphaSim corrected). Negative correlations were found between the fALFF in the left precentral gyrus and vertical CR-MI discrepancy of bilateral temporomandibular joints of patients (P<0.05, two-tailed). At T2, the symptoms and signs of the patients were improved, and a stable condylar position on the CR was recovered, with increased fALFF in the left precentral gyrus and left posterior insula compared with pretreatment. The fALFF decrease in the patients before treatment was no longer evident at T2 compared with the controls. The results suggested that TMD patients with CR-MI discrepancy showed significantly decreased brain activity in their frontal cortexes. The stabilization splint elicited functional recovery in these cortical areas. These findings provided insight into the cortical neuroplastic processes underlying TMD with CR-MI discrepancy and the therapeutic mechanisms of stabilization splint. PMID- 25110817 TI - Promoting national blood systems in developing countries. AB - PURPOSE OF REVIEW: Over the last decade, there has been increased global attention dedicated to improving the availability, safety and use of blood in low income and middle-income countries. These efforts have focused on a number of common objectives, such as establishing a 100% voluntary nonremunerated blood donor base and implementing component therapy. Recently, some of these objectives have been challenged. This article reviews many recent findings of the experts leading these international projects. RECENT FINDINGS: The majority of current research is focused on blood donation and patient blood management in sub-Saharan Africa, with contributions to other fields of blood safety in Latin America, the Caribbean and Asia. Countries collecting blood from the replacement donors are challenging the notion that replacement donors are inherently a higher risk group than voluntary donors. Simultaneously, many countries are considering how best to improve the management of their blood inventories and to optimize their national standards, guidelines and protocols - all with the goal of improving patient outcomes. SUMMARY: There still exist many questions in the areas of blood donation and clinical use that are either unanswered or merit further investigation. Given the variable circumstances observed between different countries and geographic regions, it sometimes may be advisable to limit global recommendations in favor of the regionally focused ones. PMID- 25110818 TI - Catalytic generation of vinylthionium ions. (4 + 3)-Cycloadditions and Friedel Crafts alkylations. AB - A 3-phenylsulfanyl-substituted allylic alcohol and an ester thereof were treated with Bronsted acids or a gold catalyst, respectively, to generate vinylthionium ions. These species react with dienes, primarily substituted furans, to give products of either (4 + 3)-cycloaddition or Friedel-Crafts alkylation. The results are rationalized on the basis of a stepwise mechanism in which the relative rates of ring closure versus proton loss in the intermediate sigma complex determine the course of the reaction. PMID- 25110819 TI - Incidence of and risk factors for involvement of the central nervous system in acute myeloid leukemia. AB - It is thought that the low incidence of central nervous system (CNS) involvement in acute myeloid leukemia (AML) does not justify routine CNS prophylaxis, as high dose cytarabine eliminates CNS disease. To investigate whether chemotherapy that does not include high-dose cytarabine increases the risk of CNS involvement, the medical records of 1412 newly diagnosed patients with AML were reviewed. In 1370 patients, lumbar puncture (LP) was performed only if clinically indicated, and CNS disease was detected in 45 (3.3%) patients. Another 42 patients underwent routine LP as part of an investigational protocol, and in eight (19%) CNS disease was detected (p < 0.0001). Risk factors included high lactate dehydrogenase, African-American ethnicity and young age. Patients receiving high-dose cytarabine and those who did not had similar rates of CNS involvement. Disease-free survival (DFS) and overall survival were shorter in patients with CNS involvement. It remains to be determined whether routine CNS prophylaxis would improve DFS. PMID- 25110820 TI - Pharmacogenetic studies in children with acute lymphoblastic leukemia in Argentina. AB - The aim of this study was to evaluate the influence of the most common genetic variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred and eighty-six patients with ALL treated with two Berlin-Frankfurt-Munster (BFM) based protocols were analyzed. Ten genetic variants were studied. Toxicity was evaluated during the consolidation phase. Children who received 2 g/m(2)/day of methotrexate and carried at least one 677T allele in MTHFR showed an increased risk of developing severe leukopenia (p = 0.004) and neutropenia (p = 0.003). Intermediate-risk (IR) patients with a heterozygous TPMT genotype had a higher probability of event-free survival than those with a wild-type genotype. Genotyping of MTHFR polymorphisms might be useful to optimize consolidation therapy, reducing the associated severe hematologic toxicity. Further studies are necessary to establish the usefulness of MTHFR and TPMT variants as additional markers to predict outcome in the IR group. PMID- 25110821 TI - Hepatitis B virus infection correlates with poor prognosis of extranodal natural killer/T cell lymphoma. AB - Studies have shown that hepatitis B virus (HBV) infection may play an important role in the lymphomagenesis of lymphoma, but no studies regarding the relationship between HBV infection and extranodal natural killer/T cell lymphoma (ENKTL) have been reported previously. One hundred and seven patients diagnosed with ENKTL were retrospectively reviewed. The hepatitis B surface antigen (HBsAg) positive rate was 13.1%, and no significant correlation existed between HBV infection and clinical characteristics (p > 0.05). No significant difference existed in complete remission rate between HBsAg-positive and -negative groups (42.9% vs. 44.1%, p = 1.000). In a multivariate Cox regression model that included international prognostic index (IPI) score, induction chemotherapy regimen and HBsAg status, all these variables were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) (p < 0.05). In conclusion, the HBsAg-positive rate in ENKTL was similar to that of the normal population in a high HBV endemic area, and HBsAg-positive status was an independent prognostic factor for OS and PFS. PMID- 25110822 TI - Underlying autoimmune diseases are not aggravated during treatment with lenalidomide in patients with mucosa-associated lymphoid tissue lymphoma: author's reply. PMID- 25110823 TI - Aggressive congenital juvenile myelomonocytic leukemia associated with somatic KRAS p.G13D mutation and concurrent germline IGF1R duplication. PMID- 25110824 TI - Extended treatment with brentuximab vedotin in patients with relapsed or refractory CD30-positive hematological malignancies. PMID- 25110825 TI - Comprehensive geriatric assessment is an essential tool to support treatment decisions in elderly patients with diffuse large B-cell lymphoma: a prospective multicenter evaluation in 173 patients by the Lymphoma Italian Foundation (FIL). AB - We performed a multicenter study to validate the concept that a simple comprehensive geriatric assessment (CGA) can identify elderly, non-fit patients with diffuse large B-cell lymphoma (DLBCL) in whom curative treatment is not better then palliation, and to analyze potential benefits of treatment modulation after further subdividing the non-fit category by CGA criteria. One hundred and seventy-three patients aged > 69 treated with curative or palliative intent by clinical judgement only were grouped according to CGA into fit (46%), unfit (16%) and frail (38%) categories. Two-year overall survival (OS) was significantly better in fit than in non-fit patients (84% vs. 47%; p < 0.0001). Survival in unfit and frail patients was not significantly different. Curative treatment slightly improved 2-year OS in unfit (75% vs. 45%) but not in frail patients (44% vs. 39%). CGA was confirmed as very efficient in identifying elderly patients with DLBCL who can benefit from a curative approach. Further efforts are needed to better tailor therapies in non-fit patients. PMID- 25110826 TI - Cyclic and acyclic fructose conformers in the gas phase: a large-scale second order perturbation theory study. AB - We performed large-scale second-order perturbation theory gas-phase calculations to study about five hundred structures of D-fructose. The two lowest energy fructose structures identified are beta-pyranoses possessing (2)C5 chair, with DeltaG(298 K) of 6 kJ/mol, differing in orientation of the equatorially positioned hydroxymethyl group, gt and g'g, where the gt rotamer is the global minimum, consistent with the recent microwave spectroscopy study. We have found that interconversions from the fructose global minimum to the second and third most stable beta-pyranose rotamers involve the energy barriers of ca. 30 kJ/mol. Among numerous fructofuranose conformers discovered (about 250), a pair of the ((3)T2) alpha- and (E3) beta-anomers are energetically most preferred and lie at least 12 kJ/mol above the global minimum. We also found that the fructose open chain structures lie significantly higher in energy than the most stable cyclic species. The commonly used M06-2X density functional performs well compared to MP2 and G4 theory at identifying the low-energy fructose minima, including the global one, and at reproducing their intramolecular H-bond geometric parameters. The lowest-energy gas-phase pyranose and furanose structures of fructose benefit from stabilization due to the cooperative or quasi-linear H-bonding and both endo and exo anomeric effects. PMID- 25110827 TI - Antibody informatics for drug discovery. AB - More and more antibody therapeutics are being approved every year, mainly due to their high efficacy and antigen selectivity. However, it is still difficult to identify the antigen, and thereby the function, of an antibody if no other information is available. There are obstacles inherent to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii) antibody numbering and IMGT. Here, we review "antibody informatics," which may integrate the above three fields so that bridging the gaps between industrial needs and academic solutions can be accelerated. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. PMID- 25110828 TI - Lycopene attenuates insulin signaling deficits, oxidative stress, neuroinflammation, and cognitive impairment in fructose-drinking insulin resistant rats. AB - Fructose intake is linked with the increasing prevalence of insulin resistance, and insulin resistance links Alzheimer's disease with impaired insulin signaling, oxidative damage, neuroinflammation, and cognitive impairment. As a member of the carotenoid family of phytochemicals, lycopene is used as a potent free scavenger, and has been demonstrated to be effective in anti-oxidative stress and anti inflammatory reaction in the models of AD and other neurodegenerative diseases. Here, we investigated the effect of lycopene on learning and memory impairment and the possible underlying molecular events in fructose-drinking insulin resistant rats. We found that long-term fructose-drinking causes insulin resistance, impaired insulin signaling, oxidative stress, neuroinflammation, down regulated activity of cholinergic system, and cognitive impairment, which could be significantly ameliorated by oral lycopene administration. The results from this study provide experimental evidence for using lycopene in the treatment of brain damage caused by fructose-drinking insulin resistance. PMID- 25110830 TI - Clinical effectiveness of interventions for treatment-resistant anxiety in older people: a systematic review. AB - BACKGROUND: Anxiety and related disorders include generalised anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder and phobic disorders (intense fear of an object or situation). These disorders share the psychological and physical symptoms of anxiety, but each disorder has its own set of characteristic symptoms. Anxiety disorders can be difficult to recognise, particularly in older people (those aged over 65 years). Older people tend to be more reluctant to discuss mental health issues and there is the perception that older people are generally more worried than younger adults. It is estimated that between 3 and 14 out of every 100 older people have an anxiety disorder. Despite treatment, some people will continue to have symptoms of anxiety. People are generally considered to be 'resistant' or 'refractory' to treatment if they have an inadequate response or do not respond to their first treatment. Older adults with an anxiety disorder find it difficult to manage their day-to-day lives and are at an increased risk of comorbid depression, falls, physical and functional disability, and loneliness. OBJECTIVE: To evaluate the effectiveness of pharmacological, psychological and alternative therapies in older adults with an anxiety disorder who have not responded, or have responded inadequately, to treatment. DATA SOURCES: Electronic databases (MEDLINE, MEDLINE In-Process and Other Non-Indexed citations, EMBASE, The Cochrane Library databases, PsycINFO and Web of Science) were searched from inception to September 2013. Bibliographies of relevant systematic reviews were hand-searched to identify additional potentially relevant studies. ClinicalTrials.gov was searched for ongoing and planned studies. REVIEW METHODS: A systematic review of the clinical effectiveness of treatments for treatment-resistant anxiety in older adults was carried out. RESULTS: No randomised controlled trial or prospective comparative observational study was identified meeting the prespecified inclusion criteria. Therefore, it was not possible to draw any conclusions on clinical effectiveness. LIMITATIONS: As no study was identified in older adults, there is uncertainty as to which treatments are clinically effective for older adults with an anxiety disorder who have not responded to prior treatment. The comprehensive methods implemented to carry out this review are a key strength of the research presented. However, this review highlights the extreme lack of research in this area, identifying no comparative studies, which is a marked limitation. CONCLUSIONS: Specific studies evaluating interventions in older adults with an anxiety disorder who have not responded to first-line treatment are needed to address the lack of evidence. The lack of evidence in this area means that older adults are perhaps receiving inappropriate treatment or are not receiving a particular treatment because there is limited evidence to support its use. At this time there is scope to develop guidance on service provision and, as a consequence, to advance the standard of care received by older adults with a treatment-resistant anxiety disorder in primary and secondary care. Evaluation of the relative clinical effectiveness and acceptability of pharmacological and psychological treatment in older adults with an anxiety disorder that has not responded to first-line treatment is key future research to inform decision-making of clinicians and patients. An important consideration would be the enrolment of older adults who would be representative of older adults in general, i.e. those with multiple comorbid physical and mental disorders who might require polypharmacy. STUDY REGISTRATION: The protocol for the systematic review is registered on PROSPERO (registration number CRD42013005612). FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 25110831 TI - Progression of DNA damage induced by a glyphosate-based herbicide in fish (Anguilla anguilla) upon exposure and post-exposure periods--insights into the mechanisms of genotoxicity and DNA repair. AB - Roundup(r) is a glyphosate-based herbicide widely used with both agricultural and non-agricultural purposes, which has been demonstrated to represent a risk to non target aquatic organisms, namely fish. Among the described effects to fish, genotoxicity has been pointed out as one of the most hazardous. However, the genotoxic mechanisms of Roundup(r) as well as the involvement of the oxidative DNA damage repair system are not entirely understood. Hence, this work aimed to improve the knowledge on the progression of DNA damage upon short-term exposure (3 days) and post-exposure (1-14 days) periods in association with DNA repair processes in Anguilla anguilla exposed to Roundup(r) (58 and 116 MUg L-1). DNA damage in hepatic cells was evaluated by the comet assay improved with the DNA lesion specific endonucleases FPG and EndoIII. In order to evaluate the oxidative DNA damage repair ability, an in vitro base excision repair (BER) assay was performed, testing hepatic subcellular extracts. Besides the confirmation of the genotoxic potential of this herbicide, oxidative damage was implicit as an important mechanism of genetic damage, which showed to be transient, since DNA integrity returned to the control levels on the first day after cessation of exposure. An increased capacity to repair oxidative DNA damage emerging in the post-exposure period revealed to be a crucial pathway for the A. anguilla recovery; nevertheless, DNA repair machinery showed to be susceptible to inhibitory actions during the exposure period, disclosing another facet of the risk associated with the tested agrochemical. PMID- 25110832 TI - Liquid/Liquid interfacial fabrication of thermosensitive and catalytically active Ag nanoparticle-doped block copolymer composite foam films. AB - An aqueous solution of AgNO3 (upper phase) and a DMF/CHCl3 solution of polystyrene-b-poly(acryl acid)-b-polystyrene (PS-b-PAA-b-PS) or PS-b-PAA-b-PS/1,6 diaminohexane (DAH) (lower phase) constituted a planar liquid/liquid interface. The lower phase gradually transformed to a water-in-oil (W/O) emulsion via spontaneous emulsification due to the "ouzo effect". Polymer molecules, DAH molecules, and Ag(+) ions assembled into microcapsules around emulsion droplets that adsorbed at the planar liquid/liquid interface, resulting in formation of a foam film. DAH acted as a cross-linker during this process. Transmission electron microscopic observations indicated that Ag nanoclusters that were generated through reduction of Ag(+) ions by DMF were homogeneously dispersed in the walls of the foam structure. X-ray photoelectron spectroscopic investigations revealed that Ag(I) and Ag(0) coexisted in the film, and Ag(I) transformed to Ag(0) after further treatment. The film formed without DAH was not stable, while the film formed with DAH was very stable due to intermolecular attraction between PAA and DAH and formation of amides, as revealed by FTIR spectra. The film formed with DAH exhibited high and durable catalytic activity for hydrogenation of nitro compounds and, very interestingly, exhibited thermoresponsive catalytic behavior. PMID- 25110834 TI - Successful embolization of iatrogenic ruptured coronary artery using Onyx: a new technique. AB - Iatrogenic perforation of coronary artery is rare during percutaneous coronary intervention (PCI); however the complications are life-threatening. Patients in this clinical setting may be treated either by stent placement, closure of the perforation with fibrin glue or coils, or with emergency bypass surgery. Onyx, a new material that has been used successfully in cerebral arteries, represents a new and safe alternative. The advantage of Onyx is that it is easily injected through a microcatheter and it allows for a longer injection time having also the ability to reach difficult anatomical locations. We present the first case of successful embolization of a right coronary artery perforation during coronary angiography using Onyx. PMID- 25110833 TI - Molecular speciation and dynamics of oxidized triacylglycerols in lipid droplets: Mass spectrometry and coarse-grained simulations. AB - Lipid droplets (LDs) are ubiquitous and physiologically active organelles regulating storage and mobilization of lipids in response to metabolic demands. Among the constituent LD neutral lipids, such as triacylglycerols, cholesterol esters, and free fatty acids, oxidizable polyunsaturated molecular species may be quite abundant, yet the structural and functional roles of their oxidation products have not been studied. Our previous work documented the presence of these peroxidized species in LDs. Assuming that hydrophilic oxygen-containing functionalities may markedly change the hydrophobic/hydrophilic molecular balance, here we utilized computational modeling to test the hypothesis that lipid peroxidation causes redistribution of lipids between the highly hydrophobic core and the polar surface (phospho)lipid monolayer-the area enriched with integrated enzymatic machinery. Using quantitative liquid chromatography/mass spectrometry, we characterized molecular speciation of oxTAGs in LDs of dendritic cells in cancer and hypoxic trophoblasts cells as two cellular models associated with dyslipidemia. Among the many types of oxidized lipids identified, we found that oxidatively truncated forms and hydroxyl derivatives of TAGs were the prevailing oxidized lipid species in LDs in both cell types. Using coarse-grained molecular dynamics (CG-MD) simulations we established that lipid oxidation changed their partitioning whereby oxidized lipids migrated into the outer monolayer of the LD, where they can affect essential metabolic pathways and undergo conversions, possibly leading to the formation of oxygenated lipid mediators. PMID- 25110835 TI - Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence both HBV infection and hepatocellular carcinoma development. AB - Zinc ribbon domain containing 1 (ZNRD1), cloned from human leukocyte antigen (HLA) region, may play integral roles in diverse processes including immune response against HBV infection and hepatocarcinogenesis. ZNRD1-AS1 (ZNRD1 antisense RNA 1) may be an important regulator of ZNRD1. By bioinformatics analyses, we identified that several single nucleotide polymorphisms (SNPs) in ZNRD1-AS1 may be expression quantitative trait loci (eQTLs) for ZNRD1. In this study, we hypothesized that these eQTLs SNPs in ZNRD1-AS1 may influence both chronic HBV infection and hepatocellular carcinoma (HCC) development. We designed a case-control study of 1300 HBV-positive HCC patients, 1344 HBV persistent carriers and, 1344 HBV natural clearance subjects to test the associations of three ZNRD1 eQTLs SNPs (rs3757328, rs6940552 and, rs9261204) in ZNRD1-AS1 with the risk of both chronic HBV infection and HCC. Logistic regression analyses in additive genetic model showed that variant alleles of all the three SNPs increased host HCC risk, whereas variant allele of rs3757328 was associated with HBV clearance. Moreover, the haplotype containing variant alleles of the three SNPs was significantly associated with both HCC development (adjusted OR = 1.18, 95% CI = 1.01-1.38, P = 0.035) and HBV clearance (adjusted OR = 0.83, 95% CI = 0.71-0.96, P = 0.013), when compared with the most frequent haplotype. In vitro experiments showed that ZNRD1 knockdown inhibited the expression of HBV mRNA and promoted proliferation of HepG2.2.15 cells. These findings suggest that ZNRD1 regulatory SNPs may be susceptibility makers for risk of both chronic HBV infection and HCC. PMID- 25110836 TI - Alcohol abuse and ERP components in Go/No-go tasks using alcohol-related stimuli: impact of alcohol avoidance. AB - Alcohol addictive behaviors are associated with a combination of deficits in executive functions, such as a weak response inhibition, and potent automatic appetitive responses to alcohol-related cues. The aim of the present study was to investigate behavioral responses and event-related potentials (ERPs) associated with specific response inhibition for alcohol-related cues. Thirty participants (15 heavy drinkers and 15 light drinkers) took part in the study. Response inhibition was assessed by a classical letter Go/No-go task and by a modified alcohol Go/No-go task. Participants were also classified as high and low alcohol avoiders. Results showed that heavy drinkers made more false alarms in the letter Go/No-go task. In the alcohol Go/No-go task, an absence of N200 amplitude anteriorization was found in heavy drinkers as compared to light drinkers. Participants with a high level of alcohol avoidance exhibited more false alarms, and higher N200 amplitude for the No-go trials as compared to the Go trials for alcohol-related cues. Higher P300 amplitude was observed in low alcohol avoiders for No-go as compared to Go trials. Therefore, a context involving alcohol related cues disturbed inhibition capacities of high alcohol avoiders. These results suggest that the level of alcohol avoidance must be taken into account in studies investigating alcohol-related cognitive biases. PMID- 25110838 TI - Gender-age interaction in incidence rates of childhood emotional disorders. AB - BACKGROUND: The post-pubertal association of female gender with emotional disorder is a robust finding. However, studies exploring the association of gender and emotional disorders before puberty are few and present diverging results. The aim of this study was to present gender-specific incidence rates of emotional disorders throughout childhood. METHOD: This is a population-based cohort study of 907,806 Danish 3- to 18-year-olds. The outcome was assignment of an emotional disorder diagnosis based on in-patient and out-patient data from The Danish Psychiatric Central Register. Outcome measures were incidence rates and cumulative incidences for unipolar depressive disorder (ICD-10: F32-F33), anxiety disorders (ICD-10: F40-F42), and emotional disorders with onset specific to childhood (ICD-10: F93). RESULTS: Pre-pubertal incidence rates for depressive and anxiety disorders were higher for boys than girls. At age 12 years the pattern reversed. The cumulative incidence for any emotional disorder (F32-F33, F40-F42, F93) on the 11th birthday was 0.52% (95% CI 0.50-0.55) for boys and 0.31% (95% CI 0.29-0.33) for girls. On the 19th birthday cumulative incidence was 2.33% (95% CI 2.24-2.43) for boys and 3.77% (95% CI 3.64-3.90) for girls. The pre-pubertal male preponderance was also significant for depressive disorders (F32-F33, p = 0.00144) and anxiety disorders (F40-F42, F93, p < 0.00001) separately. CONCLUSIONS: Emotional disorders seem to display a male preponderance before the age of 12 years and a female preponderance thereafter. Studies exploring this gender-age interaction are needed. Still, the results question the general assumption that females throughout the lifespan are more at risk for emotional disorders than males. PMID- 25110839 TI - Treatment type and demographic characteristics as predictors for cancer adjustment: Prospective trajectories of depressive symptoms in a population sample. AB - OBJECTIVE: Prospectively identifying individuals at heightened risk for depression can alleviate the disease burden of distal physical and mental health consequences after cancer onset. Our objective was to identify heterogeneous trajectories of adjustment in cancer patients, using treatment-type as a predictor. METHODS: Participants were followed for 6 years within the Health and Retirement Study (HRS), a prospective population-based cohort study. The sample consisted of 1,294 middle-aged participants who were assessed once before and 3 time points after their report of an initial cancer diagnosis. In addition to self-reported depressive symptoms, subjects indicated receipt of surgical, radiological, or chemical interventions as part of their usual oncological care. RESULTS: Four symptom trajectories were identified with Latent Growth Mixture Modeling: an increasing depression (10.5%), chronic depression (8.0%), depressed improved (7.8%), and stable-low depression (73.7%). A conditional model using participants with available predictor data (n = 545) showed individuals in the emerging depression class were significantly more likely to have received chemo/medication therapy when compared with the remitting depression, stable-low, and chronic depression classes. Participants in the chronic and depressed improved classes generally had worse baseline health, and the depressed-improved were also younger in age. CONCLUSION: Patients who exhibited increasing depressive symptoms had a greater probability of receiving chemo/medication therapy than any other adjustment trajectory group, although the majority of chemotherapy patients did not exhibit depressive symptom changes. These data underscore the diversity of ways that patients adjust to cancer, and suggest cancer treatment, baseline health, and age may influence long-term patterns of psychological adjustment. PMID- 25110842 TI - A cross-sectional analysis of the association between perceived network social control and telomere length. AB - OBJECTIVE: Social control in the health domain refers to attempts by social network members to get an individual to modify their health behaviors. According to the dual effects model of social control, having one's health behavior controlled by others should be related to healthier behavioral change, but might arouse psychological distress as one may resent being controlled. Despite potential healthy behavior change, the stress of social control may thus be detrimental as interpersonal stress has been related to negative health outcomes. In the present study, the association between perceived social control and telomere length was tested to examine its association to biological outcomes. METHOD: In this cross-sectional study, a relatively healthy community sample of 140 middle age and older adults completed measures of perceived social control, perceived stress, and health behaviors. Peripheral blood mononuclear cells were used to determine telomere length. RESULTS: Main results showed that higher levels of perceived direct social network control were associated with shorter telomere length. These links were not influenced by statistical controls for medication use, self-rated health, trait hostility, and optimism. Perceived social control was also related to greater perceived stress but not health behaviors overall. However, neither perceived stress nor health behaviors mediated the link between social control and telomere length. CONCLUSIONS: Although the study design precludes strong inferences, these results suggest that perceived social control may be associated with cellular aging. These data also highlight the utility of integrating biological outcomes into social control models. (PsycINFO Database Record PMID- 25110840 TI - Distress and type 2 diabetes-treatment adherence: A mediating role for perceived control. AB - OBJECTIVE: To better understand independent pathways linking emotional distress, medication adherence, and glycemic control in adults with Type 2 diabetes, as well as the potential mediating effects of perceived control over illness and self-efficacy. METHOD: Adults with Type 2 diabetes (N = 142) were recruited for an intervention study evaluating cognitive-behavioral therapy for adherence and depression. Depressive symptom severity was assessed via semistructured interview. Validated self-reports assessed diabetes-related distress, perceived control over diabetes (perceived control), self-efficacy for diabetes self management, and medication adherence. Glycemic control was evaluated by hemoglobin A1C. Only baseline data were included in correlational and linear regression analyses. RESULTS: Perceived control was an important mediator of emotional distress for both medication adherence and A1C outcomes. Specifically, regression analyses demonstrated that diabetes distress, but not depression severity, was significantly related to medication adherence and A1C. Self efficacy and perceived control were also independently associated with medication adherence and A1C. Mediation analyses demonstrated a significant indirect effect for diabetes distress and medication adherence through perceived control and self efficacy. The relationship between distress and A1C was accounted for by an indirect effect through perceived control. CONCLUSION: Results demonstrated that diabetes-related emotional distress is associated with poorer treatment adherence and glycemic control among adults with Type 2 diabetes; these relationships were partially mediated through perceived control over diabetes. Perceptions of one's personal ability to influence the course of diabetes may be important in understanding the pathway between emotional distress and poor diabetes-treatment outcomes. PMID- 25110841 TI - HIV/STI risk-reduction intervention efficacy with South African adolescents over 54 months. AB - OBJECTIVE: Little research has tested HIV/sexually transmitted infection (STI) risk-reduction interventions' effects on early adolescents as they age into middle and late adolescence. This study tested whether intervention-induced reductions in unprotected intercourse during a 12-month period endured over a 54 month period and whether the intervention reduced the prevalence of STIs, which increase risk for HIV. METHOD: Grade 6 learners (mean age = 12.4 years) participated in a 12-month trial in Eastern Cape Province, South Africa, in which 9 matched pairs of schools were randomly selected and within pairs randomized to a theory-based HIV/STI risk-reduction intervention or an attention-control intervention. They completed 42- and 54-month postintervention measures of unprotected intercourse (the primary outcome), other sexual behaviors, theoretical constructs, and, at 42- and 54-month follow-up only, biologically confirmed curable STIs (chlamydial infection, gonorrhea, and trichomoniasis) and herpes simplex virus 2. RESULTS: The HIV/STI risk-reduction intervention reduced unprotected intercourse averaged over the entire follow-up period (OR = 0.42, 95% CI [0.22, 0.84]), an effect not significantly reduced at 42- and 54-month follow up compared with 3-, 6-, and 12-month follow-ups. The intervention caused positive changes on theoretical constructs averaged over the 5 follow-ups, although most effects weakened at long-term follow-up. Although the intervention's main effect on STIs was nonsignificant, an Intervention Condition * Time interaction revealed that it significantly reduced curable STIs at 42 month follow-up in adolescents who reported sexual experience. CONCLUSION: These results suggest that theory-based behavioral interventions with early adolescents can have long-lived effects in the context of a generalized severe HIV epidemic. PMID- 25110843 TI - Anger arousal and behavioral anger regulation in everyday life among patients with chronic low back pain: Relationships to patient pain and function. AB - OBJECTIVE: The objective of this study was to determine the degree to which patient anger arousal and behavioral anger regulation (expression, inhibition) occurring in the course of daily life was related to patient pain and function as rated by patients and their spouses. METHOD: Married couples (N = 105) (one spouse with chronic low back pain) completed electronic daily diaries, with assessments 5 times/day for 14 days. Patients completed items on their own state anger, behavioral anger expression and inhibition, and pain-related factors. Spouses completed items on their observations of patient pain-related factors. Hierarchical linear modeling was used to test concurrent and lagged relationships. RESULTS: Patient-reported increases in state anger were related to their reports of concurrent increases in pain and pain interference and to spouse reports of patient pain and pain behavior. Patient-reported increases in behavioral anger expression were related to lagged increases in pain intensity and interference and decreases in function. Most of these relationships remained significant with state anger controlled. Patient-reported increases in behavioral anger inhibition were related to concurrent increases in pain interference and decreases in function, which also remained significant with state anger controlled. Patient-reported increases in state anger were related to lagged increases in spouse reports of patient pain intensity and pain behaviors. CONCLUSIONS: Results indicate that in patients with chronic pain, anger arousal and behavioral anger expression and inhibition in everyday life are related to elevated pain intensity and decreased function as reported by patients. Spouse ratings show some degree of concordance with patient reports. PMID- 25110844 TI - Peers promoting physical activity among breast cancer survivors: A randomized controlled trial. AB - OBJECTIVE: Although studies have shown that physical activity (PA) can reduce some treatment-related side effects of breast cancer, there is a need to offer PA programs outside of research settings to reach more cancer survivors. We partnered with the American Cancer Society's Reach to Recovery (RTR) program to train their volunteers (breast cancer survivors) to deliver a 12-week PA intervention to other breast cancer survivors. METHOD: We conducted a randomized controlled trial to compare the PA intervention delivered by RTR volunteers (PA plus RTR) with contact control (RTR control). Eighteen RTR volunteers/coaches (Mage = 54.9 years; Mtime since diagnosis = 7.0 years) delivered the contact control condition or the PA intervention. Seventy-six breast cancer survivors in New England (Mage = 55.6 years; Mtime since diagnosis = 1.1 years) were randomized to 1 of the 2 groups. At baseline, 12 weeks (postintervention), and at 24 weeks, participants wore an accelerometer for 7 days, were interviewed about their PA, and reported their motivational readiness for PA. RESULTS: Adjusted, mixed-effects longitudinal regression models showed significant group differences favoring the PA plus RTR group in minutes of moderate to vigorous PA at 12 weeks (Mdifference = 103 min/week, p < .001) and at 24 weeks (Mdifference = 34.7 min/week, p = .03). Results were corroborated with significant group differences in accelerometer data favoring the PA plus RTR group at both time points. CONCLUSION: Peer volunteers were able to significantly increase PA among cancer survivors relative to contact control. Partnerships with existing volunteer programs can help to widen the reach of behavioral interventions among cancer survivors. (PsycINFO Database Record PMID- 25110845 TI - Hostility and the risk of peptic ulcer in the GAZEL cohort. AB - OBJECTIVE: Evidence for an association between hostility and peptic ulcer mainly relies on cross-sectional studies. Prospective studies are rare and have not used a validated measure of hostility. This prospective study aimed to examine the association between hostility and peptic ulcer in the large-scale French GAZEL cohort. METHOD: In 1993, 14,674 participants completed the Buss and Durkee Hostility Inventory. Participants were annually followed-up from 1994 to 2011. Diagnosis of peptic ulcer was self-reported. The association between hostility scores and ulcer incidence was measured by hazard ratios (HR) and 95% confidence intervals computed through Cox regression. RESULTS: Among 13,539 participants free of peptic ulcer history at baseline, 816 reported a peptic ulcer during a mean follow-up of 16.8 years. Adjusting for potential confounders, including smoking, occupational grade, and a proxy for nonsteroidal anti-inflammatory drug exposure, ulcer incidence was positively associated with total hostility (HR per SD: 1.23, confidence interval: 1.14-1.31), behavioral hostility (HR per SD: 1.13, confidence interval: 1.05-1.21), cognitive hostility (HR per SD: 1.26, confidence interval: 1.18-1.35), and irritability (HR per SD: 1.20, confidence interval: 1.12-1.29). The risk of peptic ulcer increased from the lowest to the highest quartile for all hostility measures (p for linear trend < .05). CONCLUSIONS: Hostility might be associated with an increased risk of peptic ulcer. Should these results be replicated, further studies would be needed to explore the underlying mechanisms. PMID- 25110846 TI - Racial and sexual minority women's receipt of medical assistance to become pregnant. AB - OBJECTIVE: This study aimed to determine rates at which racial minority (i.e., non-White) and sexual minority (i.e., lesbian and bisexual-identified) women in the United States receive medical help to become pregnant. Income and insurance coverage discrepancies were hypothesized to mediate differences in receipt of medical help as a function of race and sexual orientation. METHOD: Two studies compared rates at which adult women ages 21-44 reported receiving medical help to become pregnant as a function of race and sexual orientation, using data from 2 cycles of the National Survey of Family Growth (the 2002 wave in Study 1, and the 2006-2010 wave in Study 2). Mediation analyses controlling for age and education level evaluated whether race and sexual orientation were positively associated with receipt of medical pregnancy help, as mediated by insurance coverage and income. RESULTS: Heterosexual White women reported receiving medical fertility assistance at nearly double the rates of women who identified as non-White, sexual minority, or both. Differences in rates of help received by White and non White groups were only partially mediated by insurance coverage and income in both studies. Insurance and income discrepancies accounted for all differences between sexual minority and heterosexual women's receipt of pregnancy help in Study 1; insurance coverage alone explained differences in Study 2. CONCLUSIONS: Researchers often indicate that economic differences are responsible for health disparities between minority and majority groups, but this may not be the case for all women pursuing medical fertility assistance. Possible origins of these disparities are discussed. PMID- 25110847 TI - Medication beliefs mediate between depressive symptoms and medication adherence in cystic fibrosis. AB - OBJECTIVE: Depression is a known barrier to regimen adherence for chronic conditions. Despite elevated depression rates and complex regimens for people with cystic fibrosis (CF), little is known about associations between depressive symptoms and CF adherence. One possibility is that depressive symptoms distort beliefs about medications, which may influence adherence. METHOD: Adolescents and adults (N = 128; mean age = 29 +/- 11 years, range = 16-63, 93% Caucasian) with CF reported on depressive symptoms and medication beliefs (self-efficacy, motivation, perceived importance, and outcome expectancies related to taking medications). Medication adherence was assessed objectively through pharmacy refill data. Cross-sectional structural equation models evaluated medication beliefs as a mediator between depressive symptoms and medication adherence. RESULTS: Twenty-three percent of participants exceeded clinical cutoffs for depressive symptoms. Participants took less than half of prescribed pulmonary medications (mean adherence rate = 44.4 +/- 26.7%). Depressive symptoms were correlated with adherence (r = -.22, p < .05), and medication beliefs (b = -0.13, 95% CI [-0.24, -0.03]) significantly mediated this relation. Higher depressive symptoms were associated with less positive medication beliefs (b = -0.27, p < .01), which were associated with lower medication adherence (b = 0.49, p < .01). CONCLUSIONS: Depressive symptoms are related to beliefs about and adherence to CF medications. Monitoring depressive symptoms and medication beliefs in routine CF care may help identify risks for nonadherence and facilitate interventions to reduce depression, adaptive medication beliefs, and ultimately improve adherence and CF management. (PsycINFO Database Record PMID- 25110848 TI - Prepregnancy body mass index, gestational weight gain, and elevated depressive symptoms in a Hispanic cohort. AB - OBJECTIVES: Our objective was to assess the associations among prepregnancy Body Mass Index (BMI), gestational weight gain (GWG), and elevated depressive symptoms across pregnancy. METHODS: We evaluated these associations among 1,090 participants in Proyecto Buena Salud, a prospective cohort study of Hispanic (predominantly Puerto Rican) women in Western Massachusetts. BMI and GWG were self-reported; GWG was classified according to the 2009 Institute of Medicine guidelines. Depressive symptoms were assessed in early, mid-, and late pregnancy using the 10-item Edinburgh Postnatal Depression Scale (EPDS). We defined elevated depressive symptoms as EPDS scores >=13 and >=15. RESULTS: In multivariable, longitudinal modeling, overweight (25.0 to <30 kg/m2) women had an odds ratio of 0.53 (95% CI [0.31, 0.90]) for EPDS scores >=13 and 0.51 (95% CI [0.28, 0.91]) for EPDS scores >=15 compared to normal weight women. We did not observe an association between GWG or an interaction between BMI and GWG, in predicting elevated depressive symptoms. CONCLUSIONS: Our findings provide preliminary support for an association of prepregnancy overweight status and lower depressive symptoms across pregnancy in Hispanic women. Future research should focus on potential social and cultural differences in perceptions of weight and weight gain in the perinatal period and how these influence psychological health. PMID- 25110849 TI - Capability to care: supporting the health of informal caregivers for older people. AB - OBJECTIVE: The study investigated the capabilities important to the health of people caring informally for elders. METHOD: Over 4 months, 60 informal caregivers from New Zealand participated in online discussion boards that provided a set of virtual forums. It drew upon the Capability Approach (Sen, 1980) to frame a qualitative inquiry whereby participants could anonymously respond to an evolving joint discussion of their health needs. Template analysis based on Nussbaum's (2007) list of essential human capabilities informed the thematic analysis. RESULTS: The results showed the interconnected nature of capabilities and the importance of emotions in informal caregiving. Emotional attachment influenced the caregivers' freedom to choose how they lived their lives. Because they valued the capability to care for loved ones, the caregivers traded other capabilities, putting their lives on hold, and compromising their wellbeing. CONCLUSION: The self-abnegation reported by the caregivers highlighted the relational nature of caregiving and challenged a dominant perspective in the caregiving literature that focuses on the burdens of caregiving. The significance of emotional aspects related to the valued capabilities of caregiving suggests the need to acknowledge caregiving as an interdependent relationship and emotions as a crucial place to focus future support for caregivers. PMID- 25110850 TI - Examining the moderating effect of depressive symptoms on the relation between exercise and self-efficacy during the initiation of regular exercise. AB - OBJECTIVE: People with depressive symptoms report lower levels of exercise self efficacy and are more likely to discontinue regular exercise than others, but it is unclear how depressive symptoms affect the relation between exercise and self efficacy. We sought to clarify whether depressive symptoms moderate the relations between exercise and same-day self-efficacy, and between self-efficacy and next day exercise. METHODS: Participants (n = 116) were physically inactive adults (35% reported clinically significant depressive symptoms) who initiated regular exercise and completed daily assessments for 4 weeks. Mixed linear models were used to test whether (a) self-efficacy differed on days when exercise did and did not occur, (b) self-efficacy predicted next-day exercise, and (c) these relations were moderated by depressive symptoms. RESULTS: First, self-efficacy was lower on days when no exercise occurred, but this difference was larger for people with high depressive symptoms (p < .001). They had lower self-efficacy than people with low depressive symptoms on days when no exercise occurred (p = .03), but self-efficacy did not differ on days when exercise occurred (p = .34). Second, self-efficacy predicted greater odds of next-day exercise, OR = 1.12, 95% [1.04, 1.21], but depressive symptoms did not moderate this relation, OR = 1.00, 95% CI [.99, 1.01]. CONCLUSIONS: During exercise initiation, daily self-efficacy is more strongly related to exercise occurrence for people with high depressive symptoms than those with low depressive symptoms, but self-efficacy predicts next-day exercise regardless of depressive symptoms. The findings specify how depressive symptoms affect the relations between exercise and self-efficacy and underscore the importance of targeting self-efficacy in exercise interventions, particularly among people with depressive symptoms. (PsycINFO Database Record PMID- 25110851 TI - Posttraumatic stress disorder and responses to couple conflict: implications for cardiovascular risk. AB - OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with increased risk of coronary heart disease (CHD) and difficulties in intimate relationships. Greater frequency and severity of couple conflict and greater cardiovascular reactivity to such conflict might contribute to CHD risk in those with PTSD, but affective and physiological responses to couple conflict have not been examined previously in this population. METHOD: In a preliminary test of this hypothesis, 32 male veterans of the Iraq and Afghanistan Wars with PTSD and their female partners, and 33 control male veterans without PTSD and their female partners completed relationship quality assessments and a conflict discussion task. PTSD diagnosis was confirmed through diagnostic interviews and questionnaires. State anger, state anxiety, and cardiovascular measures (i.e., blood pressure, heart rate) were recorded during baseline and the conflict discussion. RESULTS: Compared with controls, PTSD couples reported greater couple conflict and less warmth, and displayed pronounced increases in anger and greater increases in systolic blood pressure in response to the conflict task (all ps < .05; range eta2: .05-.24). Partners in the PTSD group exhibited similar, if not greater, responses as veterans. CONCLUSIONS: This was the first investigation to document emotional and cardiovascular responses to couple conflict in veterans with PTSD and their partners. PTSD was associated with greater frequency and severity of couple conflict, and greater anger and cardiovascular reactivity to conflict discussions. Anger and physiological responses to couple discord might contribute to CHD risk in veterans with PTSD, and perhaps their partners, as well. PMID- 25110852 TI - Expression of executive control in situational context: Effects of facilitating versus restraining cues on snack food consumption. AB - OBJECTIVES: To examine the effects of executive function (EF) on objectively measured high-calorie snack food consumption in 2 age groups and to explore the moderating influence of environmental cues. METHODS: In Study 1, 43 older adults (M(age) = 74.81) and in Study 2, 79 younger adults (M(age) = 18.71) completed measures of EF and subsequently participated in a bogus taste-test paradigm wherein they were required to rate 3 highly appetitive (but high-calorie) snack foods on taste and texture. Grams of snack food consumed was measured covertly in the presence randomly assigned contextual cues (explicit semantic cues in Study 1; implicit visual cues in Study 2) that were facilitating or restraining in nature. RESULTS: Findings indicated that in both age groups, stronger EF predicted lower consumption of snack foods across conditions, and the effects of EF were most pronounced in the presence of facilitating cues. CONCLUSIONS: Older and younger adults with weaker EF tend to consume more high-calorie snack food compared with their stronger EF counterparts. These tendencies appear to be especially amplified in the presence of facilitating cues. PMID- 25110853 TI - Caregivers' burden and depressive symptoms: the moderational role of attachment orientations. AB - OBJECTIVE: The current study explored whether attachment orientations moderate the associations between caregiver burden and depressive symptoms among women coping with their partners' first time acute coronary syndrome. The association between burden and depression was hypothesized to be stronger among caregivers high on anxious attachment than among caregivers low on this dimension. In addition, the association between burden and depressive symptoms was hypothesized to be weaker among caregivers higher on avoidant attachment than among those lower on this dimension. METHOD: The sample consisted of 111 female caregivers of male patients admitted to the cardiac care unit of a hospital in Israel. Caregivers completed a measure of attachment orientations during patients' hospitalization (baseline). Caregiver burden was measured 1 month later. Depressive symptoms were measured at baseline and again at 6-month follow-up. Structural equation modeling was used to test the moderational models. RESULTS: The association between caregiver burden and depressive symptoms at follow-up was moderated by attachment-related anxiety but not attachment-related avoidance. Congruent with predictions, a stronger association between caregiver burden and depressive symptoms occurred for caregivers with greater (vs. lower) attachment anxiety. CONCLUSIONS: The findings shed light on the possible dynamics among attachment orientations and affect regulation when coping with one's partner's illness. The findings are discussed in light of Pietromonaco, Uchino, and Dunkel Schetter's (2013) model of integrating attachment into health psychology research. PMID- 25110854 TI - Modeling the association between lifecourse socioeconomic disadvantage and systemic inflammation in healthy adults: The role of self-control. AB - OBJECTIVE: We sought to identify pathways connecting lifecourse socioeconomic status (SES) with chronic, low-grade inflammation, focusing on the explanatory roles of self-control, abdominal adiposity, and health practices. METHODS: Participants were 360 adults aged 15-55 who were free of chronic medical conditions. They were roughly equally divided between low and high current SES, with each group further divided between low and high early-life SES. Structural equation modeling (SEM) was used to identify direct and indirect pathways linking early-life and current SES with low-grade, chronic inflammation in adulthood, as manifest by serum interleukin-6 and C-reactive protein. Low SES was hypothesized to relate to inflammation by reducing self-control, which in turn was hypothesized to facilitate lifestyle factors that potentiate inflammation (smoking, alcohol use, sedentary behavior, and weight gain). RESULTS: Analyses revealed that self-control was pivotal in linking both early-life and current SES to inflammation. Low early-life SES was related to a harsher family climate, and in turn lower adult self-control, over and above the effects of current SES. Controlling for early-life SES, low current SES was associated with perceived stress and, in turn, diminished self-control. Results showed that lower self control primarily operated through higher abdominal adiposity to associate with greater inflammation. CONCLUSIONS: The findings suggest a mechanistic scenario wherein low SES in early life or adulthood depletes self-control and, in turn, fosters adiposity and inflammation. These pathways should be studied longitudinally to elucidate and potentially ameliorate socioeconomic disparities in health. PMID- 25110855 TI - Ossification sequence and genetic patterning in the mouse axial skeleton. AB - We provide novel data on vertebral ontogeny in the mouse, the mammalian model-of choice for developmental studies. Most previous studies on ossification sequences in mice have focused on pooled elements of the spine (cervicals, thoracics, lumbars, sacrals, and caudals). Here, we contribute data on ossification sequences in the neural arches and centra to provide a comparative basis upon which to evaluate mammalian diversity of the axial skeleton. In attempt to explain the ossification pattern observed, we compared our observations with the phenotype of Cdx over-expresser mice. We use high-resolution X-ray microtomography and clearing and staining techniques to quantify the precise sequential ossification pattern of the mouse spine. We show that micro-CT scans perform better in all cases whereas clearing and staining exhibit sensitivity to the presence of semi-opaque tissue. We observe that the centra of wild-type mice always ossify after neural arches and that the ossification of the neural arches proceeds from two loci. The ossification of the centra appears more complex, especially in the neck where ossification is delayed and does not just follow the order of the vertebrae along the anterior-posterior axis. Our findings also suggest that Cdx genes' expression levels may be involved in the delayed ossification in the neck centra. PMID- 25110857 TI - Pregnancy outcomes of HIV-positive women in a tertiary centre in the UK. AB - With the advent of highly active antiretroviral therapy (HAART), the mother-to child HIV transmission rate in the UK has reduced to less than 2%. A review of delivery outcomes of 106 HIV-positive pregnant women in a tertiary centre between January 2005 and December 2010 was conducted. A total of 20 women had detectable plasma viral load at 36 weeks, or before in the two women who delivered preterm. Various peripartum management measures were undertaken in women with detectable viral load close to delivery, to accelerate reduction in plasma viral load and to reduce the risk of HIV transmission to the fetus. In our review, the overall mother-to-child transmission rate was less than 1% and in women with undetectable viral load at 36 weeks, it was 0% (zero), which signifies the importance of strict virological control and a multidisciplinary approach, which plays an important role in the successful achievement of this. PMID- 25110856 TI - Closure versus non-closure of the peritoneum at caesarean section: short- and long-term outcomes. AB - BACKGROUND: Caesarean section is a very common surgical procedure worldwide. Suturing the peritoneal layers at caesarean section may or may not confer benefit, hence the need to evaluate whether this step should be omitted or routinely performed. OBJECTIVES: The objective of this review was to assess the effects of non-closure as an alternative to closure of the peritoneum at caesarean section on intraoperative and immediate- and long-term postoperative outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 November 2013). SELECTION CRITERIA: Randomised controlled trials comparing leaving the visceral or parietal peritoneum, or both, unsutured at caesarean section with a technique which involves suturing the peritoneum in women undergoing elective or emergency caesarean section. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked it for accuracy. MAIN RESULTS: A total of 29 trials were included in this review and 21 trials (17,276 women) provided data that could be included in an analysis. The quality of the trials was variable. 1. Non-closure of visceral and parietal peritoneum versus closure of both parietal layersSixteen trials involving 15,480 women, were included and analysed, when both parietal peritoneum was left unclosed versus when both peritoneal surfaces were closed. Postoperative adhesion formation was assessed in only four trials with 282 women, and no difference was found between groups (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.76 to 1.29). There was significant reduction in the operative time (mean difference (MD) -5.81 minutes, 95% CI -7.68 to -3.93). The duration of hospital stay in a total of 13 trials involving 14,906 women, was also reduced (MD -0.26, 95% CI -0.47 to -0.05) days. In a trial involving 112 women, reduced chronic pelvic pain was found in the peritoneal non-closure group. 2. Non-closure of visceral peritoneum only versus closure of both peritoneal surfacesThree trials involving 889 women were analysed. There was an increase in adhesion formation (two trials involving 157 women, RR 2.49, 95% CI 1.49 to 4.16) which was limited to one trial with high risk of bias.There was reduction in operative time, postoperative days in hospital and wound infection. There was no significant reduction in postoperative pyrexia. 3. Non-closure of parietal peritoneum only versus closure of both peritoneal layersThe two identified trials involved 573 women. Neither study reported on postoperative adhesion formation. There was reduction in operative time and postoperative pain with no difference in the incidence of postoperative pyrexia, endometritis, postoperative duration of hospital stay and wound infection. In only one study, postoperative day one wound pain assessed by the numerical rating scale, (MD -1.60, 95% CI -1.97 to -1.23) and chronic abdominal pain d by the visual analogue score (MD -1.10, 95% CI -1.39 to -0.81) was reduced in the non-closure group. 4. Non-closure versus closure of visceral peritoneum when parietal peritoneum is closed.There was reduction in all the major urinary symptoms of frequency, urgency and stress incontinence when the visceral peritoneum is left unsutured. AUTHORS' CONCLUSIONS: There was a reduction in operative time across all the subgroups. There was also a reduction in the period of hospitalisation post-caesarean section except in the subgroup where parietal peritoneum only was not sutured where there was no difference in the period of hospitalisation. The evidence on adhesion formation was limited and inconsistent. There is currently insufficient evidence of benefit to justify the additional time and use of suture material necessary for peritoneal closure. More robust evidence on long-term pain, adhesion formation and infertility is needed. PMID- 25110858 TI - Diffusion NMR of molecular cages and capsules. AB - In the last decade diffusion NMR and diffusion ordered spectroscopy (DOSY) have become important analytical tools for the characterization of supramolecular systems in solution. Diffusion NMR can be used to glean information on the (effective) size and shape of molecular species, as well as to probe inter molecular interactions and can be used to estimate the association constant (Ka) of a complex. In addition, the diffusion coefficient, as obtained from diffusion NMR, is a much more intuitive parameter than the chemical shift for probing self association, aggregation and inter-molecular interactions. The diffusion coefficient may be an even more important analytical parameter in systems in which the formed supramolecular entity has the same symmetry as its building units, when there is a large change in the molecular weight, where many molecular species are involved in the formation of the supramolecular systems, and when proton transfer may occur which, in turn, may affect the chemical shift. Some of the self-assembled molecular capsules and cages prepared in the last decade represent such supramolecular systems and in the present review, following a short introduction on diffusion NMR, we survey the contribution of diffusion NMR and DOSY in the field of molecular containers and capsules. We will first focus on the role played by diffusion NMR in the field of hydrogen bond driven self assembled capsules. We then survey the contributions of diffusion NMR and DOSY to the study and characterization of metal-ligand cages and capsules. Finally, we describe a few recent applications of diffusion NMR in the field of hydrophobic, electrostatic and covalent containers. PMID- 25110859 TI - The role of doppler waveforms in the fetal main pulmonary artery in the prediction of neonatal respiratory distress syndrome. AB - OBJECTIVE: To describe changes in the Doppler waveforms of the fetal main pulmonary artery (MPA) throughout gestation and to assess their predictive value of neonatal respiratory distress syndrome (RDS). STUDY DESIGN: In the first phase of this study, we performed Doppler measurement of MPA acceleration time (AT), ejection time (ET), peak systolic velocity, end-diastolic velocity, mean velocity, pulsatility index, and resistance index in 288 healthy fetuses. In the second phase, we carried out these measurements in a prospective cohort of 52 pregnant women with impending preterm birth. RESULTS: In phase I, satisfactory fetal MPA Doppler recordings were collected in 284 of 288 (98.6%) normal fetuses. Significant and positive linear correlations were found between gestational age and AT, AT/ET ratio, peak systolic velocity, and mean velocity (p < 0.01), with the strongest correlations concerning AT (r = 0.898) and AT/ET ratio (r = 0.868). In phase II, satisfactory fetal MPA Doppler waveforms were obtained in 43 of 44 (97.7%) fetuses. Of these, 14 (32.6%) developed RDS and 29 did not. Using less than or equal to the fifth percentile as a gestational age-specific cutoff, AT alone could predict RDS with a sensitivity of 78.6% and a specificity of 89.7%. The AT/ET ratio could predict RDS with 71.4% sensitivity and 93.1% specificity. CONCLUSIONS: Fetal MPA Doppler velocimetry can reliably be obtained throughout gestation. AT and AT/ET ratios of the fetal MPA Doppler waveform may help identifying fetuses at risk of developing neonatal RDS. PMID- 25110860 TI - Large and fast single-crystal resistive humidity sensitivity of metal pnictide halides containing van der Waals host-guest interactions. AB - Two new metal pnictide halides, (Hg(9.75)As(5.5))(GaCl4)3 and (Hg13Sb8)(ZnBr4)4, have been prepared by solid-state reactions. Their structures feature 3D cationic host frameworks built of mercury pnictide polyhedra and form 1D tunnels filled with discrete guest halide polyanions; the guests and hosts are assembled by van der Waals interactions. Both complexes exhibit good single-crystal humidity sensitivity, with a humidity sensitivity factor as big as three orders of magnitude, a quick resistance response, fast recovery, and good reproducibility. This study provide a new way to design promising resistive humidity detectors by introducing van der Waals host-guest interactions into their structures. PMID- 25110861 TI - Mid-level practitioners in dermatology: a need for further study and oversight. PMID- 25110862 TI - Robust non-wetting PTFE surfaces by femtosecond laser machining. AB - Nature shows many examples of surfaces with extraordinary wettability,which can often be associated with particular air-trapping surface patterns. Here,robust non-wetting surfaces have been created by femtosecond laser ablation of polytetrafluoroethylene (PTFE). The laser-created surface structure resembles a forest of entangled fibers, which support structural superhydrophobicity even when the surface chemistry is changed by gold coating. SEM analysis showed that the degree of entanglement of hairs and the depth of the forest pattern correlates positively with accumulated laser fluence and can thus be influenced by altering various laser process parameters. The resulting fibrous surfaces exhibit a tremendous decrease in wettability compared to smooth PTFE surfaces; droplets impacting the virgin or gold coated PTFE forest do not wet the surface but bounce off. Exploratory bioadhesion experiments showed that the surfaces are truly air-trapping and do not support cell adhesion. Therewith, the created surfaces successfully mimic biological surfaces such as insect wings with robust anti-wetting behavior and potential for antiadhesive applications. In addition, the fabrication can be carried out in one process step, and our results clearly show the insensitivity of the resulting non-wetting behavior to variations in the process parameters,both of which make it a strong candidate for industrial applications. PMID- 25110863 TI - A sensitive and effective proteomic approach to identify she-donkey's and goat's milk adulterations by MALDI-TOF MS fingerprinting. AB - She-donkey's milk (DM) and goat's milk (GM) are commonly used in newborn and infant feeding because they are less allergenic than other milk types. It is, therefore, mandatory to avoid adulteration and contamination by other milk allergens, developing fast and efficient analytical methods to assess the authenticity of these precious nutrients. In this experimental work, a sensitive and robust matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) profiling was designed to assess the genuineness of DM and GM milks. This workflow allows the identification of DM and GM adulteration at levels of 0.5%, thus, representing a sensitive tool for milk adulteration analysis, if compared with other laborious and time-consuming analytical procedures. PMID- 25110864 TI - Biosurfactant mediated biosynthesis of selected metallic nanoparticles. AB - Developing a reliable experimental protocol for the synthesis of nanomaterials is one of the challenging topics in current nanotechnology particularly in the context of the recent drive to promote green technologies in their synthesis. The increasing need to develop clean, nontoxic and environmentally safe production processes for nanoparticles to reduce environmental impact, minimize waste and increase energy efficiency has become essential in this field. Consequently, recent studies on the use of microorganisms in the synthesis of selected nanoparticles are gaining increased interest as they represent an exciting area of research with considerable development potential. Microorganisms are known to be capable of synthesizing inorganic molecules that are deposited either intra- or extracellularly. This review presents a brief overview of current research on the use of biosurfactants in the biosynthesis of selected metallic nanoparticles and their potential importance. PMID- 25110865 TI - BMP4 protects rat pulmonary arterial smooth muscle cells from apoptosis by PI3K/AKT/Smad1/5/8 signaling. AB - Bone morphogenetic protein-4 (BMP4), a member of the transforming growth factor beta (TGF-beta) family of growth factors, is activated and increased under hypoxic conditions, which plays an important role in the progression of pulmonary arterial hypertension (PAH). Previous studies have shown that BMP4 is involved in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. However, the precise mechanisms involved in the regulation of pulmonary artery smooth muscle cells (PASMCs) in PAH are still incompletely understood. It has been reported that AKT is a critical regulator of cell survival and vascular remodeling. Therefore, there may be crosstalk between BMP4 anti-apoptotic processes and PI3K/AKT survival effect in rat PASMCs. To test this hypothesis, we performed confocal, cell viability measurement, mitochondrial potential, real-time polymerase chain reaction (PCR), and Western blot analysis to determine the role of BMP4 on cell survival and apoptosis. We found that hypoxia up-regulated the expression of BMP4. BMP4 promoted cell survival, reduced mitochondrial depolarization, and increased the expression of Bcl-2 and procaspase-3 in PASMCs under serum-deprived condition. These effects were reversed by PI3K/AKT inhibitors (LY294002 and wortmannin). Thus, these findings indicate that BMP4 protects PASMCs from apoptosis at least in part, mediated via the PI3K/AKT pathway. PMID- 25110866 TI - Lutein inhibits the migration of retinal pigment epithelial cells via cytosolic and mitochondrial Akt pathways (lutein inhibits RPE cells migration). AB - During the course of proliferative vitreoretinopathy (PVR), the retinal pigment epithelium (RPE) cells will de-differentiate, proliferate, and migrate onto the surfaces of the sensory retina. Several studies have shown that platelet-derived growth factor (PDGF) can induce migration of RPE cells via an Akt-related pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells migration was examined using transwell migration assays and Western blot analyses. We found that both phosphorylation of Akt and mitochondrial translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed by lutein. Furthermore, the increased migration observed in RPE cells with overexpressed mitochondrial Akt could also be suppressed by lutein. Our results demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through the inhibition of both cytoplasmic and mitochondrial Akt activation. PMID- 25110868 TI - The inflammation-related gene S100A12 is positively regulated by C/EBPbeta and AP 1 in pigs. AB - S100A12 is involved in the inflammatory response and is considered an important marker for many inflammatory diseases in humans. Our previous studies indicated that the S100A12 gene was abundant in the immune tissues of pigs and was significantly upregulated during infection with Haemophilus parasuis (HPS) or porcine circovirus type 2 (PCV2). In this study, the mechanism of transcriptional regulation of S100A12 was investigated in pigs. Our results showed that S100A12, CCAAT/enhancer-binding protein beta (C/EBPbeta) and activator protein-1 (AP-1) genes were up-regulated in PK-15 (ATCC, CCL-33) cells when treated with LPS or Poly I: C. Additionally, the promoter activity and expression level of the S100A12 gene were significantly upregulated when C/EBPbeta or AP-1 were overexpressed. We utilized electromobility shift assays (EMSA) to confirm that C/EBPbeta and AP-1 could directly bind the S100A12 gene promoter. We also found that the transcriptional activity and expression levels of C/EBPbeta and AP-1 could positively regulate each other. Furthermore, the promoter activity of the S100A12 gene was higher when C/EBPbeta and AP-1 were cotransfected than when they were transfected individually. We concluded that the S100A12 gene was cooperatively and positively regulated by C/EBPbeta and AP-1 in pigs. Our study offers new insight into the transcriptional regulation of the S100A12 gene. PMID- 25110869 TI - Richter's transformation to diffuse large B-cell lymphoma: a retrospective study reporting clinical data, outcome, and the benefit of adding rituximab to chemotherapy, from the Israeli CLL Study Group. AB - Richter's syndrome (RS) is the rare development of an aggressive lymphoid malignancy in a patient with pre-existing chronic lymphocytic leukemia (CLL). Data on RS is sparse and mostly derived from case reports or small series of patients and only a few larger cohorts have been published. The purpose of this large retrospective study was to summarize our national experience with RS in CLL, examine possible risk factors, and analyze relevant demographic, laboratory and clinical parameters, including results of therapy and outcome. We first evaluated data obtained from 119 patients with RS diagnosed during 1971-2010 from 12 medical centers in Israel. The final cohort summarized consisted of 81 patients with RS who developed only diffuse large B-cell lymphoma (DLBCL) after exclusion all cases with insufficient data and those who were not DLBCL. Median overall survival from time of diagnosis of RS was 8 months; after applying the Richter score, patients could be stratified into three prognostic groups, while all other clinical and laboratory parameters evaluated had no prognostic significance. Prior therapy for CLL had no impact on RS survival (P = 0.8) and patients with therapy "naive" RS and those who had already received chemotherapy prior to developing RS, had the same survival. The addition of rituximab to chemotherapy for RS improved 2 years overall survival from 19% in the chemotherapy alone arm to 42% (P value of 0.001). Although prognosis of patients with RS remains dismal, this retrospective observation provides support for the use of chemo-immunotherapy in DLBCL-RS. PMID- 25110870 TI - Graphene oxide and laponite composite films with high oxygen-barrier properties. AB - The design and fabrication of oxygen barrier films is important for both fundamental and industrial applications. We prepared three different thin films composed of graphene oxide (GO) and laponite (LN), a typical low cost inorganic clay, with the GO/LN volume ratios of 1.9/0.1, 1.7/0.3 and 1.5/0.5 together with a double layer film of the GO and LN. We found that the films with GO/LN = 1.9/0.1 and the double layers exhibited high oxygen barrier and oxygen transmission rate values that reached 0.55 and 0.37 cm(3) per m(2) per atm per day, respectively, which were much lower than those of the films prepared from the pure GO, only LN and GO/LN = 1.7/0.3 and 1.5/0.5. This study is important for the design and fabrication of a film from GO-based all inorganic nanomaterials for applications in gas-barrier membranes. PMID- 25110871 TI - Endoscopist Fatigue May Contribute to a Decline in the Effectiveness of Screening Colonoscopy. AB - GOALS: To assess whether endoscopist fatigue adversely affects the adenoma detection rate (ADR) during screening colonoscopy. BACKGROUND: Endoscopist fatigue may affect the ADR during colonoscopy; however, this association has not been directly studied. STUDY: A prospective, multi-center study was performed on screening colonoscopies performed for asymptomatic subjects between March 2012 and December 2012 in Korea. Endoscopist fatigue was defined and measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. The ADR was compared between fatigued endoscopists and nonfatigued endoscopists, and a multivariate regression analysis was performed to identify independent factors related to the detection of colorectal adenoma. RESULTS: During the study period, a total of 457 subjects underwent screening colonoscopy. After excluding 62 subjects, outcomes of 395 subjects were analyzed. The overall ADR of the study population was 39.7%. The mean score of FACIT-F was 36.4+/-10.8, and a cutoff score of 25 was chosen to define fatigue. The ADR was lower in fatigued endoscopists than nonfatigued endoscopists (25.0% vs. 42.6%, P=0.008). Using multivariate regression analysis, endoscopist fatigue measured with FACIT-F (odds ratio=3.585; 95% confidence interval, 1.663-7.728; P=0.001) was found to be an independent factor for the ADR. CONCLUSIONS: FACIT-F score may be a novel measure for endoscopist fatigue, and ADR was adversely influenced by endoscopist fatigue measured by FACIT-F. Our results suggest that endoscopist fatigue may contribute to a decline in the effectiveness of screening colonoscopy. PMID- 25110872 TI - Esophageal Stenting With Sutures: Time to Redefine Our Standards? AB - BACKGROUND AND STUDY AIMS: Migration is the most common complication of the fully covered metallic self-expanding esophageal stent (FCSEMS). Recent studies have demonstrated migration rates between 30% and 60%. The aim of this study was to determine the effect of fixation of the FCSEMS by endoscopic suturing on migration rate. PATIENT AND METHODS: Patients who underwent stent placement for esophageal strictures and leaks over the last year were captured and reviewed retrospectively. Group A, cases, were patients who underwent suture placement and group B, controls, were patients who had stents without sutures. Basic demographics, indications, and adverse events (AEs) were collected. Kaplan-Meier analysis and Cox regression modeling were conducted to determine estimates and predictors of stent migration in patients with and without suture placement. RESULTS: Thirty-seven patients (18 males, 48.65%), mean age 57.2 years (+/-16.3 y), were treated with esophageal FCSEMS. A total of 17 patients received sutures (group A) and 20 patients received stents without sutures (group B). Stent migration was noted in a total of 13 of the 37 patients (35%) [2 (11%) in group A and 11 (55%) in group B]. Using Kaplan-Meier analysis and log-rank analysis, fixation of the stent with suturing reduced the risk of migration (P=0.04). There were no AEs directly related to suture placement. CONCLUSIONS: Anchoring of the upper flare of the FCSEMS with endoscopic sutures is technically feasible and significantly reduces stent migration rate when compared with no suturing, and is a safe procedure with very low AEs rates. PMID- 25110867 TI - Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies. AB - Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK-TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK-TKIs have been developed for the treatment of cancer patients. Specific/selective RTK-TKIs have shown less deleterious effects compared to multi-targeted inhibitors. This review intends to highlight the importance of specific/selective TKIs for future development with less side effects and more manageable agents. This article provides an overview of: (1) the characteristics and function of RTKs and TKIs; (2) the recent advances in the improvement of specific/selective RTK-TKIs in preclinical or clinical settings; and (3) emerging RTKs for targeted cancer therapies by TKIs. PMID- 25110873 TI - The role of domperidone in increasing the completion rate of small bowel capsule endoscopy: how should it be used? PMID- 25110874 TI - Identifying all at-risk patients for Clostridium difficile infection. PMID- 25110875 TI - Lynch-like syndrome: characterization and comparison with EPCAM deletion carriers. AB - Colorectal cancers (CRCs) with microsatellite instability-high (MSI+) but without detectable germline mutation or hypermethylation in DNA mismatch repair (MMR) genes can be classified as Lynch-like syndrome (LLS). The underlying mechanism and clinical significances of LLS are largely unknown. We measured MSI and MMR protein expression in 4,765 consecutive CRC cases. Among these, MSI+ cases were further classified based on clinical parameters, germline sequencing of MMR genes or polymerase epsilon (POLE) and delta (POLD1) and promoter methylation analysis of MLH1 and MSH2. We found that MSI+ and MMR protein-deficient CRCs comprised 6.3% (N = 302) of this cohort. On the basis of germline sequencing of 124 cases, we identified 54 LS with MMR germline mutation (LS-MMR), 15 LS with EPCAM deletions (LS-EPCAM) and 55 LLS patients. Of the 55 LLS patients, six (10.9%) had variants of unknown significance in the genes tested, and one patient had a novel somatic mutation (p.S459P) in POLE. In patients with biallelic deletions of EPCAM, all tumors and their matched normal mucosa showed promoter hypermethylation of MSH2. Finally, we found that patients with LLS and LS-EPCAM shared clinical features that differed from LS-MMR patients, including lower frequency of fulfillment of the revised Bethesda guidelines (83.6 and 86.7% vs. 98.1% for LS-MMR) and older mean age at CRC diagnosis (52.6 and 52.7 years vs. 43.9 years for LS-MMR). We identified somatic mutation in POLE as a rare underlying cause for MMR deficiency in LLS. The similarity between LLS and LS EPCAM suggests LLS as a subset of familial MSI+ CRC. PMID- 25110876 TI - Hematopoietic stem cell transplantation of an adolescent with neurological manifestations of homozygous missense PRF1 mutation. AB - Individuals with biallelic truncating PRF1 mutations typically present with fulminant early-onset familial hemophagocytic lymphohistiocytosis (FHL). We report a 19-year-old male with a 5-year history of recurrent fever and headaches progressing to refractory seizures. Brain imaging revealed multiple ring enhancing lesions. Laboratory investigations demonstrated that the patient displayed defective lymphocyte cytotoxicity and carried a homozygous missense PRF1 mutation, c.394G > A (p.Gly132Arg). The patient was successfully treated with chemo-immunotherapy followed by matched related allogeneic hematopoietic stem cell transplantation (HSCT). Our findings demonstrate that prompt HSCT of late-onset FHL with primarily neurological manifestation can reverse central nervous system symptoms and improve long-term outcome. PMID- 25110877 TI - Cyclotrimerization of arylalkynes on Au(111). AB - Surface-assisted cyclotrimerization of arylalkynes was studied on Au(111) by means of scanning tunneling microscopy (STM) under ultra-high vacuum (UHV) conditions. Upon thermal activation, cyclotrimerization of 1,3,5-tris-(4 ethynylphenyl)benzene proceeds readily and with high selectivity, and results in two-dimensional covalently bonded polyphenylene nanostructures exhibiting a honeycomb topology. PMID- 25110878 TI - Hospital relationships with direct-to-consumer screening companies. PMID- 25110879 TI - Cancer family caregiver depression: are religion-related variables important? AB - OBJECTIVE: Prevalence estimates for clinical depression among cancer family caregivers (CFC) range upwards to 39%. Research inconsistently reports risk for CFC depressive symptoms when evaluating age, gender, ethnicity, or length of time as caregiver. The discrepant findings, coupled with emerging literature indicating religiosity may mitigate depression in some populations, led us to investigate religion-related variables to help predict CFC depressive symptoms. METHODS: We conducted a cross-sectional study of 150 CFC. Explanatory variables included age, gender, spousal status, length of time as caregiver, attendance at religious services, and prayer. The outcome variable was the Center for Epidemiological Studies Depression Scale score. RESULTS: Compared with large national and state datasets, our sample has lower representation of individuals with no religious affiliation (10.7% vs. 16.1% national, p = 0.07 and 23.0% state, p = 0.001), higher rate of attendance at religious services (81.3% vs. 67.2% national, p < 0.001 and 30.0% state, p < 0.001), and higher rate of prayer (65.3% vs. 42.9% national, p < 0.001; no state data available). In unadjusted and adjusted models, prayer is not significantly associated with caregiver depressive symptoms or clinically significant depressive symptomology. Attendance at religious services is associated with depressive symptoms (p = 0.004) with an inversely linear trend (p = 0.002). CONCLUSION: The significant inverse association between attendance at religious services and depressive symptoms, despite no association between prayer and depressive symptoms, indicates that social or other factors may accompany attendance at religious services and contribute to the association. Clinicians can consider supporting a CFC's attendance at religious services as a potential preventive measure for depressive symptoms. PMID- 25110880 TI - Contribution of human immunodeficiency virus type 1 minority variants to reduced drug susceptibility in patients on an integrase strand transfer inhibitor-based therapy. AB - The role of HIV-1 minority variants on transmission, pathogenesis, and virologic failure to antiretroviral regimens has been explored; however, most studies of low-level HIV-1 drug-resistant variants have focused in single target regions. Here we used a novel HIV-1 genotypic assay based on deep sequencing, DEEPGEN (Gibson et al 2014 Antimicrob Agents Chemother 58?2167) to simultaneously analyze the presence of minority variants carrying mutations associated with reduced susceptibility to protease (PR), reverse transcriptase (RT), and integrase strand transfer integrase inhibitors (INSTIs), as well as HIV-1 coreceptor tropism. gag p2/NCp7/p1/p6/pol-PR/RT/INT and env/C2V3 PCR products were obtained from twelve heavily treatment-experienced patients experiencing virologic failure while participating in a 48-week dose-ranging study of elvitegravir (GS-US-183-0105). Deep sequencing results were compared with (i) virological response to treatment, (ii) genotyping based on population sequencing, (iii) phenotyping data using PhenoSense and VIRALARTS, and (iv) HIV-1 coreceptor tropism based on the phenotypic test VERITROP. Most patients failed the antiretroviral regimen with numerous pre-existing mutations in the PR and RT, and additionally newly acquired INSTI-resistance mutations as determined by population sequencing (mean 9.4, 5.3, and 1.4 PI- RTI-, and INSTI-resistance mutations, respectively). Interestingly, since DEEPGEN allows the accurate detection of amino acid substitutions at frequencies as low as 1% of the population, a series of additional drug resistance mutations were detected by deep sequencing (mean 2.5, 1.5, and 0.9, respectively). The presence of these low-abundance HIV-1 variants was associated with drug susceptibility, replicative fitness, and coreceptor tropism determined using sensitive phenotypic assays, enhancing the overall burden of resistance to all four antiretroviral drug classes. Further longitudinal studies based on deep sequencing tests will help to clarify (i) the potential impact of minority HIV-1 drug resistant variants in response to antiretroviral therapy and (ii) the importance of the detection of HIV minority variants in the clinical practice. PMID- 25110881 TI - Acquisition of Cry1Ac protein by non-target arthropods in Bt soybean fields. AB - Soybean tissue and arthropods were collected in Bt soybean fields in China at different times during the growing season to investigate the exposure of arthropods to the plant-produced Cry1Ac toxin and the transmission of the toxin within the food web. Samples from 52 arthropod species/taxa belonging to 42 families in 10 orders were analysed for their Cry1Ac content using enzyme-linked immunosorbent assay (ELISA). Among the 22 species/taxa for which three samples were analysed, toxin concentration was highest in the grasshopper Atractomorpha sinensis and represented about 50% of the concentration in soybean leaves. Other species/taxa did not contain detectable toxin or contained a concentration that was between 1 and 10% of that detected in leaves. These Cry1Ac-positive arthropods included a number of mesophyll-feeding Hemiptera, a cicadellid, a curculionid beetle and, among the predators, a thomisid spider and an unidentified predatory bug belonging to the Anthocoridae. Within an arthropod species/taxon, the Cry1Ac content sometimes varied between life stages (nymphs/larvae vs. adults) and sampling dates (before, during, and after flowering). Our study is the first to provide information on Cry1Ac-expression levels in soybean plants and Cry1Ac concentrations in non-target arthropods in Chinese soybean fields. The data will be useful for assessing the risk of non target arthropod exposure to Cry1Ac in soybean. PMID- 25110882 TI - Identification of candidate genes associated with leaf senescence in cultivated sunflower (Helianthus annuus L.). AB - Cultivated sunflower (Helianthus annuus L.), an important source of edible vegetable oil, shows rapid onset of senescence, which limits production by reducing photosynthetic capacity under specific growing conditions. Carbon for grain filling depends strongly on light interception by green leaf area, which diminishes during grain filling due to leaf senescence. Transcription factors (TFs) regulate the progression of leaf senescence in plants and have been well explored in model systems, but information for many agronomic crops remains limited. Here, we characterize the expression profiles of a set of putative senescence associated genes (SAGs) identified by a candidate gene approach and sunflower microarray expression studies. We examined a time course of sunflower leaves undergoing natural senescence and used quantitative PCR (qPCR) to measure the expression of 11 candidate genes representing the NAC, WRKY, MYB and NF-Y TF families. In addition, we measured physiological parameters such as chlorophyll, total soluble sugars and nitrogen content. The expression of Ha-NAC01, Ha-NAC03, Ha-NAC04, Ha-NAC05 and Ha-MYB01 TFs increased before the remobilization rate increased and therefore, before the appearance of the first physiological symptoms of senescence, whereas Ha-NAC02 expression decreased. In addition, we also examined the trifurcate feed-forward pathway (involving ORE1, miR164, and ethylene insensitive 2) previously reported for Arabidopsis. We measured transcription of Ha-NAC01 (the sunflower homolog of ORE1) and Ha-EIN2, along with the levels of miR164, in two leaves from different stem positions, and identified differences in transcription between basal and upper leaves. Interestingly, Ha NAC01 and Ha-EIN2 transcription profiles showed an earlier up-regulation in upper leaves of plants close to maturity, compared with basal leaves of plants at pre anthesis stages. These results suggest that the H. annuus TFs characterized in this work could play important roles as potential triggers of leaf senescence and thus can be considered putative candidate genes for senescence in sunflower. PMID- 25110884 TI - Increased secretory leukocyte protease inhibitor (SLPI) production by highly metastatic mouse breast cancer cells. AB - The precise molecular mechanisms enabling cancer cells to metastasize from the primary tumor to different tissue locations are still largely unknown. Secretion of some proteins by metastatic cells could facilitate metastasis formation. The comparison of secreted proteins from cancer cells with different metastatic capabilities in vivo might provide insight into proteins involved in the metastatic process. Comparison of the secreted proteins from the mouse breast cancer cell line 4T1 and its highly metastatic 4T1.2 clone revealed a prominent differentially secreted protein which was identified as SLPI (secretory leukocyte protease inhibitor). Western blotting indicated higher levels of the protein in both conditioned media and whole cell lysates of 4T1.2 cells. Additionally higher levels of SLPI were also observed in 4T1.2 breast tumors in vivo following immunohistochemical staining. A comparison of SLPI mRNA levels by gene profiling using microarrays and RT-PCR did not detect major differences in SLPI gene expression between the 4T1 and 4T1.2 cells indicating that SLPI secretion is regulated at the protein level. Our results demonstrate that secretion of SLPI is drastically increased in highly metastatic cells, suggesting a possible role for SLPI in enhancing the metastatic behavior of breast cancer cell line 4T1. PMID- 25110883 TI - Genome-wide modulation of gene transcription in ovarian carcinoma cells by a new mithramycin analogue. AB - Ovarian cancer has a poor prognosis due to intrinsic or acquired resistance to some cytotoxic drugs, raising the interest in new DNA-binding agents such as mithramycin analogues as potential chemotherapeutic agents in gynecological cancer. Using a genome-wide approach, we have analyzed gene expression in A2780 human ovarian carcinoma cells treated with the novel mithramycin analogue DIG-MSK (demycarosyl-3D-beta-D-digitoxosyl-mithramycin SK) that binds to C+G-rich DNA sequences. Nanomolar concentrations of DIG-MSK abrogated the expression of genes involved in a variety of cell processes including transcription regulation and tumor development, which resulted in cell death. Some of those genes have been associated with cell proliferation and poor prognosis in ovarian cancer. Sp1 transcription factor regulated most of the genes that were down-regulated by the drug, as well as the up-regulation of other genes mainly involved in response to cell stress. The effect of DIG-MSK in the control of gene expression by other transcription factors was also explored. Some of them, such as CREB, E2F and EGR1, also recognize C/G-rich regions in gene promoters, which encompass potential DIG-MSK binding sites. DIG-MSK affected several biological processes and molecular functions related to transcription and its cellular regulation in A2780 cells, including transcription factor activity. This new compound might be a promising drug for the treatment of ovarian cancer. PMID- 25110885 TI - Quantum-classical calculation of the absorption and emission spectral shapes of oligothiophenes at low and room temperature by first-principle calculations. AB - We report a thorough computational characterization of the low- and room temperature absorption and emission spectra of a series of oligothiophenes that contain between three and seven thiophene units. Our computational approach is based on time-dependent (TD) density functional calculations with the CAM-B3LYP functional. The effect of vibrations is included without resorting to any empirical parameters either at a fully quantum level or with a hybrid quantum classical protocol. This latter approach is introduced to describe the relevant broadening effects in absorption at room temperature and is based on the partition of the vibrational modes into two sets: the inter-ring torsions treated at the anharmonic level in a classical way and the remaining modes described at the quantum level. The contribution of the quantum modes to the spectrum is computed by using a harmonic approximation, which accounts for Duschinsky mixing and changes in the vibrational frequencies associated with the electronic transition; a path-integral TD approach is adopted to account for the effect of temperature. The spectra simulated at low temperatures are in very good agreement with their experimental counterparts, which indicates that our calculations can quantitatively reproduce the effect of chain lengthening on the position and the shape of the spectra. Good agreement is also obtained at room temperature, for which we show that the classical description of the broadening, owing to the inter-ring torsions, reproduces the loss of the vibronic structure observed in the experiment and introduces only a slight overestimation of the spectral width. PMID- 25110886 TI - The effects of genetic variation in FTO rs9939609 on obesity and dietary preferences in Chinese Han children and adolescents. AB - The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25-1.71, P = 1.73*10-6), and 3.32 (95% CI: 2.01-5.47, P = 2.68*10-6), respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure (P = 0.005). Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52-5.21). The combined OR for obesity in participants with TA/AA genotypes and preference for a meat based diet was 4.04 (95% CI: 2.8-5.81) compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic variation of rs9939609 is associated with obesity and dietary preferences in Chinese children and adolescents. PMID- 25110887 TI - Functional validation and comparison framework for EIT lung imaging. AB - INTRODUCTION: Electrical impedance tomography (EIT) is an emerging clinical tool for monitoring ventilation distribution in mechanically ventilated patients, for which many image reconstruction algorithms have been suggested. We propose an experimental framework to assess such algorithms with respect to their ability to correctly represent well-defined physiological changes. We defined a set of clinically relevant ventilation conditions and induced them experimentally in 8 pigs by controlling three ventilator settings (tidal volume, positive end expiratory pressure and the fraction of inspired oxygen). In this way, large and discrete shifts in global and regional lung air content were elicited. METHODS: We use the framework to compare twelve 2D EIT reconstruction algorithms, including backprojection (the original and still most frequently used algorithm), GREIT (a more recent consensus algorithm for lung imaging), truncated singular value decomposition (TSVD), several variants of the one-step Gauss-Newton approach and two iterative algorithms. We consider the effects of using a 3D finite element model, assuming non-uniform background conductivity, noise modeling, reconstructing for electrode movement, total variation (TV) reconstruction, robust error norms, smoothing priors, and using difference vs. normalized difference data. RESULTS AND CONCLUSIONS: Our results indicate that, while variation in appearance of images reconstructed from the same data is not negligible, clinically relevant parameters do not vary considerably among the advanced algorithms. Among the analysed algorithms, several advanced algorithms perform well, while some others are significantly worse. Given its vintage and ad hoc formulation backprojection works surprisingly well, supporting the validity of previous studies in lung EIT. PMID- 25110888 TI - Human-induced changes in landscape configuration influence individual movement routines: lessons from a versatile, highly mobile species. AB - Landscape conversion by humans may have detrimental effects on animal populations inhabiting managed ecosystems, but human-altered areas may also provide suitable environments for tolerant species. We investigated the spatial ecology of a highly mobile nocturnal avian species-the red-necked nightjar (Caprimulgus ruficollis)-in two contrastingly managed areas in Southwestern Spain to provide management recommendations for species having multiple habitat requirements. Based on habitat use by radiotagged nightjars, we created maps of functional heterogeneity in both areas so that the movements of breeding individuals could be modeled using least-cost path analyses. In both the natural and the managed area, nightjars used remnants of native shrublands as nesting sites, while pinewood patches (either newly planted or natural mature) and roads were selected as roosting and foraging habitats, respectively. Although the fraction of functional habitat was held relatively constant (60.9% vs. 74.1% in the natural and the managed area, respectively), landscape configuration changed noticeably. As a result, least-cost routes (summed linear distances) from nest locations to the nearest roost and foraging sites were three times larger in the natural than in the managed area (mean +/- SE: 1356+/-76 m vs. 439+/-32 m). It seems likely that the increased proximity of functional habitats in the managed area relative to the natural one is underlying the significantly higher abundances of nightjars observed therein, where breeders should travel shorter distances to link together essential resources, thus likely reducing their energy expenditure and mortality risks. Our results suggest that landscape configuration, but not habitat availability, is responsible for the observed differences between the natural and the managed area in the abundance and movements of breeding nightjars, although no effect on body condition was detected. Agricultural landscapes could be moderately managed to preserve small native remnants and to favor the juxtaposition of functional habitats to benefit those farm species relying on patchy resources. PMID- 25110891 TI - Gene knockout and overexpression analysis revealed the role of N-acetylmuramidase in autolysis of Lactobacillus delbrueckii subsp. bulgaricus ljj-6. AB - Autolysis of lactic acid bacteria (LAB) plays a vital role in dairy processing. During cheese making, autolysis of LAB affects cheese flavor development through release of intracellular enzymes and restricts the proliferation of cells in yogurt fermentation and probiotics production. In order to explore the mechanism of autolysis, the gene for the autolytic enzymes of L. bulgaricus, N acetylmuramidase (mur), was cloned and sequenced (GenBank accession number: KF157911). Mur gene overexpression and gene knockout vectors were constructed based on pMG76e and pUC19 vectors. Recombinant plasmids were transformed into L. bulgaricus ljj-6 by electroporation, then three engineered strains with pMG76e mur vector and fifteen engineered strains with pUC19-mur::EryBII were screened. The autolysis of the mur knockout strain was significantly lower and autolysis of the mur overexpressed strain was significantly higher compared with that of the wild type strain ljj-6. This result suggested that the mur gene played an important role in autolysis of L. bulgaricus. On the other hand, autolytic activity in a low degree was still observed in the mur knockout strain, which implied that other enzymes but autolysin encoded by mur were also involved in autolysis of L. bulgaricus. PMID- 25110892 TI - Societal cost of skin cancer in Sweden in 2011. PMID- 25110893 TI - Curcumin improves hypoxia induced dysfunctions in 3T3-L1 adipocytes by protecting mitochondria and down regulating inflammation. AB - Obesity induced metabolic syndrome is increasing worldwide at an alarming rate. It is characterized by excessive expansion of white adipose tissue which leads to hypoxia and impairs normal metabolism. Recent studies reveal that hypoxia could be one of the factors for inflammation, insulin resistance and other obesity related complications. There is a high demand for anti-obese phytoceuticals to control and manage the complications resulting from obesity. In this study, we investigated how hypoxia affect the physiological functions of 3T3-L1 adipocytes emphasizing on oxidative stress, inflammation, and mitochondrial functions. We also evaluated the protective role of various doses of curcumin, a well-known dietary antioxidant, on hypoxia induced alterations. The results revealed that hypoxia significantly altered the vital parameters of adipocyte biology like HIF 1alpha expression (103.47% ?), lactate, and glycerol release (184.34% and 69.1% ?, respectively), reactive oxygen species production (432.53% ?), lipid and protein oxidation (376.6% and 566.6% ?, respectively), reduction in antioxidant enzymes (superoxide dismutase and catalase) status, secretion of inflammatory markers (TNF alpha, IL 6, IL 1beta, and IFN gamma), and mitochondrial functions (mitochondrial mass, membrane potential, permeability transition pore integrity, and superoxide generation). Curcumin substantially protected adipocytes from toxic effects of hypoxia in a dose dependent manner by protecting mitochondria and down regulating inflammation. Acriflavine is used as a positive control. A detailed investigation is required for the development of curcumin as an effective nutraceutical against obesity. PMID- 25110896 TI - Fabrication of nickel-foam-supported layered zinc-cobalt hydroxide nanoflakes for high electrochemical performance in supercapacitors. AB - Nickel foam supported Zn-Co hydroxide nanoflakes were fabricated by a facile solvothermal method. Benefited from the unique structure of Zn-Co hydroxide nanoflakes on a nickel foam substrate, the as prepared materials exhibited an excellent specific capacitance of 901 F g(-1) at 5 A g(-1) and remarkable cycling stability as electrode materials in supercapacitors. PMID- 25110897 TI - Host-guest chemistry of a water-soluble pillar[5]arene: evidence for an ionic exchange recognition process and different complexation modes. AB - The complexation of an anionic guest by a cationic water-soluble pillararene is reported. Isothermal titration calorimetry (ITC), (1)H NMR, (1)H and (19)F DOSY, and STD NMR experiments were performed to characterize the complex formed under aqueous neutral conditions. The results of ITC and (1)H NMR analyses showed the inclusion of the guest inside the cavity of the pillar[5]arene, with the binding constant and thermodynamic parameters influenced by the counter ion of the macrocycle. NMR diffusion experiments showed that although a fraction of the counter ions are expelled from the host cavity by exchange with the guest, a complex with both counter ions and the guest inside the pillararene is formed. The results also showed that at higher concentrations of guest in solution, in addition to the inclusion of one guest molecule in the cavity, the pillararene can also form an external complex with a second guest molecule. PMID- 25110898 TI - Effects of the relative values of alternatives on preference for free-choice in humans. AB - Organisms often prefer conditions that allow selection among alternatives (free choice) to conditions that do not (forced-choice), particularly when response alternatives in free-choice produce equal or greater reinforcer magnitudes than those available under forced-choice. We present data on free-choice preference for human participants who gained or lost points by selecting images of cards on a computer screen under a concurrent-chains schedule. Responding during the initial link gained access to a terminal link offering a single-card set (forced choice) or a three-card set (free-choice). The alternatives in free-choice produced reinforcer magnitudes (points) that were: (a) equal to forced-choice; (b) equal to and greater than forced-choice; and (c) equal to and less than forced-choice. Participants showed reliable preference for free-choice under some conditions; however, preference decreased as reinforcer magnitude for some alternatives in free-choice was reduced. This occurred even though it was possible to obtain the same number of points across free- and forced-choice. Although preference for free-choice was clearly demonstrated, the effect of points available in the terminal link suggests that this phenomenon is subject to modulation by other processes, such as reinforcement or punishment by obtained outcomes in the terminal link. Context (reinforcer-gain or -loss) was not a reliable predictor of preference. PMID- 25110899 TI - Prevalence of anginal symptoms and myocardial ischemia and their effect on clinical outcomes in outpatients with stable coronary artery disease: data from the International Observational CLARIFY Registry. AB - IMPORTANCE: In the era of widespread revascularization and effective antianginals, the prevalence and prognostic effect of anginal symptoms and myocardial ischemia among patients with stable coronary artery disease (CAD) are unknown. OBJECTIVE: To describe the current clinical patterns among patients with stable CAD and the association of anginal symptoms or myocardial ischemia with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: The Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) registry enrolled outpatients in 45 countries with stable CAD in 2009 to 2010 with 2-year follow-up (median, 24.1 months; range, 1 day to 3 years). Enrollees included 32 105 outpatients with prior myocardial infarction, chest pain, and evidence of myocardial ischemia, evidence of CAD on angiography, or prior revascularization. Of these, 20 291 (63.2%) had undergone a noninvasive test for myocardial ischemia within 12 months of enrollment and were categorized into one of the following 4 groups: no angina or ischemia (n = 13 207 [65.1%]); evidence of myocardial ischemia without angina (silent ischemia) (n = 3028 [14.9%]); anginal symptoms alone (n = 1842 [9.1%]); and angina and ischemia (n = 2214 [10.9%]). EXPOSURES: Stable CAD. MAIN OUTCOME AND MEASURE: The composite of cardiovascular (CV)-related death or nonfatal myocardial infarction. RESULTS: Overall, 4056 patients (20.0%) had anginal symptoms and 5242 (25.8%) had evidence of myocardial ischemia on results of noninvasive testing. Of 469 CV-related deaths or myocardial infarctions, 58.2% occurred in patients without angina or ischemia, 12.4% in patients with ischemia alone, 12.2% in patients with angina alone, and 17.3% in patients with both. The hazard ratios for the primary outcome relative to patients without angina or ischemia and adjusted for age, sex, geographic region, smoking status, hypertension, diabetes mellitus, and dyslipidemia were 0.90 (95% CI, 0.68-1.20; P = .47) for ischemia alone, 1.45 (95% CI, 1.08-1.95; P = .01) for angina alone, and 1.75 (95% CI, 1.34-2.29; P < .001) for both. Similar findings were observed for CV-related death and for fatal or nonfatal myocardial infarction. CONCLUSIONS AND RELEVANCE: In outpatients with stable CAD, anginal symptoms (with or without ischemia on noninvasive testing) but not silent ischemia appear to be associated with an increased risk for adverse CV outcomes. Most CV events occurred in patients without angina or ischemia. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN43070564. PMID- 25110900 TI - Smooth muscle cell phenotypic switch: implications for foam cell formation. AB - PURPOSE OF REVIEW: It is well accepted that LDLs and its modified form oxidized LDL (ox-LDL) play a major role in the development of atherosclerosis and foam cell formation. Whereas the majority of these cells have been demonstrated to be derived from macrophages, smooth muscle cells (SMCs) give rise to a significant number of foam cells as well. During atherosclerotic plaque formation, SMCs switch from a contractile to a synthetic phenotype. The contribution of this process to foam cell formation is still not well understood. RECENT FINDINGS: It has been confirmed that a large proportion of foam cells in human atherosclerotic plaques and in experimental intimal thickening arise from SMCs. SMC-derived foam cells express receptors involved in ox-LDL uptake and HDL reverse transport. In vitro studies show that treatment of SMCs with ox-LDL induces typical foam-cell formation; this process is associated with a transition of SMCs toward a synthetic phenotype. SUMMARY: This review summarizes data regarding the phenotypic switch of arterial SMCs within atherosclerotic lesion and their contribution to intimal foam cell formation. PMID- 25110902 TI - Characterizing Social and Recreational Programming in Assisted Living. AB - The objectives of this three-phased investigation were to (1) characterize existing recreational programming opportunities for tenants residing in assisted living (AL) and (2) gather perceptions on factors influencing activity program planning and delivery. Using an integrated knowledge translation framework during a one-year collaboration, we targeted 51 publicly funded AL sites from two health authorities in British Columbia. We conducted an activity calendar review, staff survey, and interactive symposia to identify factors that enabled or restricted recreational programming. From the information obtained, we determined that all AL sites delivered recreational programming. Although exercise and physical activity opportunities were perceived as having high importance, most activities were social. Staff reported confidence in delivering this type of programming and believed it met the holistic needs of tenants, including their mental well-being, and fostered a sense of community. Future avenues for increasing physical activity of AL tenants should address individual, site, and organizational characteristics. PMID- 25110901 TI - PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells. AB - PURPOSE OF REVIEW: Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to LDL receptor (LDLR) and targets it for lysosomal degradation in cells. Decreased hepatic clearance of plasma LDL-cholesterol is the primary gauge of PCSK9 activity in humans; however, PCSK9's evolutionary role may extend to other lipoprotein classes and processes. This review highlights studies that are providing novel insights into physiological regulation of PCSK9 transcription and plasma PCSK9 activity. RECENT FINDINGS: Recent studies indicate that circulating PCSK9 binds to apolipoprotein B100 on LDL particles, which in turn inhibits PCSK9's ability to bind to cell surface LDLRs. Negative feedback of secreted PCSK9 activity by LDL could serve to increase plasma excursion of triglyceride rich lipoproteins and monitor lipoprotein remodeling. Recent findings have identified hepatocyte nuclear factor-1alpha as a key transcriptional regulator that cooperates with sterol regulatory element-binding protein-2 to control PCSK9 expression in hepatocytes in response to nutritional and hormonal inputs, as well as acute inflammation. SUMMARY: PCSK9 is an established target for cholesterol lowering therapies. Further study of PCSK9 regulatory mechanisms may identify additional control points for pharmacological inhibition of PCSK9-mediated LDLR degradation. PCSK9 function could reflect ancient roles in the fasting-feeding cycle and in linking lipoprotein metabolism with innate immunity. PMID- 25110903 TI - Modeling sparsely clustered data: design-based, model-based, and single-level methods. AB - Recent studies have investigated the small sample properties of models for clustered data, such as multilevel models and generalized estimating equations. These studies have focused on parameter bias when the number of clusters is small, but very few studies have addressed the methods' properties with sparse data: a small number of observations within each cluster. In particular, studies have yet to address the properties of generalized estimating equations, a possible alternative to multilevel models often overlooked in behavioral sciences, with sparse data. This article begins with a discussion of population averaged and cluster-specific models, provides a brief overview of both multilevel models and generalized estimating equations, and then conducts a simulation study on the sparse data properties of generalized estimating equations, multilevel models, and single-level regression models for both normal and binary outcomes. The simulation found generalized estimating equations estimate regression coefficients and their standard errors without bias with as few as 2 observations per cluster, provided that the number of clusters was reasonably large. Similar to the previous studies, multilevel models tended to overestimate the between-cluster variance components when the cluster size was below about 5. PMID- 25110904 TI - Combating unmeasured confounding in cross-sectional studies: evaluating instrumental-variable and Heckman selection models. AB - Unmeasured confounding is the principal threat to unbiased estimation of treatment "effects" (i.e., regression parameters for binary regressors) in nonexperimental research. It refers to unmeasured characteristics of individuals that lead them both to be in a particular "treatment" category and to register higher or lower values than others on a response variable. In this article, I introduce readers to 2 econometric techniques designed to control the problem, with a particular emphasis on the Heckman selection model (HSM). Both techniques can be used with only cross-sectional data. Using a Monte Carlo experiment, I compare the performance of instrumental-variable regression (IVR) and HSM to that of ordinary least squares (OLS) under conditions with treatment and unmeasured confounding both present and absent. I find HSM generally to outperform IVR with respect to mean-square-error of treatment estimates, as well as power for detecting either a treatment effect or unobserved confounding. However, both HSM and IVR require a large sample to be fully effective. The use of HSM and IVR in tandem with OLS to untangle unobserved confounding bias in cross-sectional data is further demonstrated with an empirical application. Using data from the 2006 2010 General Social Survey (National Opinion Research Center, 2014), I examine the association between being married and subjective well-being. PMID- 25110905 TI - A comparison of procedures to test for moderators in mixed-effects meta regression models. AB - Several alternative methods are available when testing for moderators in mixed effects meta-regression models. A simulation study was carried out to compare different methods in terms of their Type I error and statistical power rates. We included the standard (Wald-type) test, the method proposed by Knapp and Hartung (2003) in 2 different versions, the Huber-White method, the likelihood ratio test, and the permutation test in the simulation study. These methods were combined with 7 estimators for the amount of residual heterogeneity in the effect sizes. Our results show that the standard method, applied in most meta-analyses up to date, does not control the Type I error rate adequately, sometimes leading to overly conservative, but usually to inflated, Type I error rates. Of the different methods evaluated, only the Knapp and Hartung method and the permutation test provide adequate control of the Type I error rate across all conditions. Due to its computational simplicity, the Knapp and Hartung method is recommended as a suitable option for most meta-analyses. PMID- 25110906 TI - Uromodulin, an emerging novel pathway for blood pressure regulation and hypertension. PMID- 25110907 TI - Construction of carbon nanotube based nanoarchitectures for selective impedimetric detection of cancer cells in whole blood. AB - A carbon nanotube (CNT) based nanoarchitecture is developed for rapid, sensitive and specific detection of cancer cells by using real time electrical impedance sensing. The sensor is constructed with carbon nanotube (CNT) multilayers and EpCAM (epithelial cell adhesion molecule) antibodies, which are assembled on an indium tin oxide (ITO) electrode surface. The binding of tumor cells to EpCAM antibodies causes increase of the electron-transfer resistance. The electrochemical impedance of the prepared biosensors is linear with the logarithm of concentration of the liver cancer cell line (HepG2) within the concentration range of 10 to 10(5) cells per mL. The detection limit for HepG2 cells is 5 cells per mL. The proposed impedimetric sensing devices allow for sensitive and specific detection of cancer cells in whole-blood samples without any sample pretreatment steps. PMID- 25110908 TI - Influence of pseudophakic lens capsule opacification on spectral domain and time domain optical coherence tomography image quality. AB - PURPOSE: To evaluate the influence of posterior capsule opacification (PCO) on optical coherence tomography (OCT) acquisition of macular retinal thickness (RT) and volume using time domain OCT (TD-OCT) and spectral domain OCT (SD-OCT). MATERIALS AND METHODS: We studied 37 eyes of 31 patients with PCO. Each patient underwent an evaluation with TD-OCT and with SD-OCT before and after Nd:YAG capsulotomy. We recorded RT and retinal volume in the macular area using only good quality images. RESULTS: Best corrected visual acuity improved in all eyes after Nd:YAG capsulotomy, with the degree of improvement ranging from 0.3 +/- 0.7 to 0.1 +/-0.7 (p = 0.01). Before the treatment, only 27% of the examinations were valuable with TD-OCT, while using SD-OCT, it was possible to obtain an examination of suitable quality both before and after the Yag laser capsulotomy in 100% of the eyes. We did not observe significant differences between mean preoperative and postoperative RT and total macular volume measurements, neither with TD-OCT nor with SD-OCT. RT and total macular volume values obtained using TD OCT were always lower than those obtained from the SD-OCT, both before and after capsulotomy. CONCLUSIONS: Our study confirmed that with old generation TD-OCT, PCO has a strong negative influence on the quality of OCT acquisition, and examination is reliable only when it is possible to acquire good quality images. With new generation SD-OCT, tomographic acquisitions are always reliable and are not influenced by the presence of PCO. PMID- 25110909 TI - Sleep-related eating disorder associated with quetiapine. PMID- 25110911 TI - Research networks in primary care: an answer to the call for better clinical research. PMID- 25110912 TI - Adaptive Parent Population Sizing in Evolution Strategies. AB - Adaptive population sizing aims at improving the overall progress of an evolution strategy. At each generation, it determines the parental population size that promises the largest fitness gain, based on the information collected during the evolutionary process. In this paper, we develop an adaptive variant of a (MU/MU, lambda) evolution strategy. Based on considerations on the sphere, we derive two approaches for adaptive population sizing. We then test these approaches empirically on the sphere model using a normalized mutation strength and cumulative mutation strength adaption. Finally, we compare the methodology on more general functions with a fixed population, covariance matrix adaption evolution strategy (CMA-ES). The results confirm that our adaptive population sizing methods yield better results than even the best fixed population size. PMID- 25110913 TI - Vaginal Dryness and Beyond: The Sexual Health Needs of Women Diagnosed With Metastatic Breast Cancer. AB - While research on the sexual health of women with early stage cancer has grown extensively over the past decade, markedly less information is available to support the sexual health needs of women diagnosed with advanced breast cancer. Semistructured interviews were conducted with 32 women diagnosed with metastatic breast cancer (ages 35 to 77) about questions they had concerning their sexual health and intimate relationships. All participants were recruited from a comprehensive cancer center at a large Midwestern university. Three themes were examined: the role of sexual activity and intimate touch in participants' lives, unmet information needs about sexual health, and communication with medical providers about sexual concerns. Findings indicated that sexual activities with partners were important; however, participants worried about their own physical limitations and reported frequent physical (e.g., bone pains) and vaginal pain associated with intercourse. When women raised concerns about these issues in clinical settings, medical providers often focused exclusively on vaginal lubricants, which did not address the entirety of women's problems or concerns. In addition, women diagnosed with metastatic breast cancer reported needing additional resources about specialized vaginal lubricants, nonpenetrative and nongenitally focused sex, and sexual positions that did not compromise their physical health yet still provided pleasure. PMID- 25110914 TI - trans-Platinum(II) complex of 3-aminoflavone - synthesis, X-ray crystal structure and biological activities in vitro. AB - This paper describes the synthesis of trans-bis-(3 aminoflavone)dichloridoplatinum(ii) (trans-Pt(3-af)2Cl2; TCAP) for use as a potential anticancer compound, and the evaluation of its structure by elemental and spectral analyses, and X-ray crystallography. The complex demonstrated a significant cytotoxic effect against human and murine cancer cell lines, as well as weaker toxicity towards healthy cells (human peripheral blood lymphocytes) in comparison with cisplatin. Various biochemical and morphological methods confirm that the proapoptotic activity of trans-Pt(3-af)2Cl2 is markedly higher than the reference cisplatin. Our results suggest that trans-Pt(3-af)2Cl2 may have a different antitumour specificity from that of cisplatin. PMID- 25110915 TI - Altered innervation of the fallopian tube in adenomyosis. PMID- 25110916 TI - MIDA as a simple and highly efficient ligand for palladium-catalyzed Hiyama cross coupling of aryl halides. AB - N-Methyliminodiacetic acid (MIDA) as a simple, air stable and water-soluble ligand has been used in the palladium-catalyzed Hiyama cross-coupling reaction of trimethoxyphenylsilane with aryl halides. The yield of the corresponding Hiyama coupling products is high up to around 90% in water and isopropanol under an ambient atmosphere in the presence of KOH and NaF. PMID- 25110917 TI - Relative and absolute stereochemistry of diacarperoxides: antimalarial norditerpene endoperoxides from marine sponge Diacarnus megaspinorhabdosa. AB - Five new norditerpene endoperoxides, named diacarperoxides H-L (1-5), and a new norditerpene diol, called diacardiol B (6), were isolated from the South China Sea sponge, Diacarnus megaspinorhabdosa. Their structures, including conformations and absolute configurations, were determined by using spectroscopic analyses, computational approaches and chemical degradation. Diacarperoxides H-J (1-3) showed some interesting stereochemical issues, as well as antimalarial activity. PMID- 25110918 TI - The skeletal amino acid composition of the marine demosponge Aplysina cavernicola. AB - It has been discovered during the past few years that demosponges of the order Verongida such as Aplysina cavernicola exhibit chitin-based skeletons. Verongida sponges are well known to produce bioactive brominated tyrosine derivatives. We could recently demonstrate that brominated compounds do not exclusively occur in the cellular matrix but also in the skeletons of the marine sponges Aplysina cavernicola and Ianthella basta. Our measurements imply that these yet unknown compounds are strongly, possibly covalently bound to the sponge skeletons. In the present work, we determined the skeletal amino acid composition of the demosponge A. cavernicola especially with respect to the presence of halogenated amino acids. The investigations of the skeletons before and after MeOH extraction confirmed that only a small amount of the brominated skeleton-bound compounds dissolves in MeOH. The main part of the brominated compounds is strongly attached to the skeletons but can be extracted for example by using Ba(OH)2. Various halogenated tyrosine derivatives were identified by GC-MS and LC-MS in these Ba(OH)2 extracts of the skeletons. PMID- 25110919 TI - Structure elucidation of five novel isomeric saponins from the viscera of the sea cucumber Holothuria lessoni. AB - Sea cucumbers are prolific producers of a wide range of bioactive compounds. This study aimed to purify and characterize one class of compound, the saponins, from the viscera of the Australian sea cucumber Holothuria lessoni. The saponins were obtained by ethanolic extraction of the viscera and enriched by a liquid-liquid partition process and adsorption column chromatography. A high performance centrifugal partition chromatography (HPCPC) was applied to the saponin-enriched mixture to obtain saponins with high purity. The resultant purified saponins were profiled using MALDI-MS/MS and ESI-MS/MS which revealed the structure of isomeric saponins to contain multiple aglycones and/or sugar residues. We have elucidated the structure of five novel saponins, Holothurins D/E and Holothurinosides X/Y/Z, along with seven reported triterpene glycosides, including sulfated and non sulfated saponins containing a range of aglycones and sugar moieties, from the viscera of H. lessoni. The abundance of novel compounds from this species holds promise for biotechnological applications. PMID- 25110920 TI - Is apolipoprotein e required for cognitive function in humans?: implications for Alzheimer drug development. PMID- 25110921 TI - Antibacterial polymeric nanostructures for biomedical applications. AB - The high incidence of bacterial infection and the growing resistance of bacteria to conventional antibiotics have resulted in the strong need for the development of new generation of antibiotics. Nano-sized particles have been considered as novel antibacterial agents with high surface area and high reactivity. The overall antibacterial properties of antimicrobial nanostructures can be significantly enhanced compared with conventional antibacterial agents not in a regular nanostructure, showing a better effect in inhibiting the growth and reproduction of microbials such as bacteria and fungi, etc. In this review, recent advances in the research and applications of antimicrobial polymeric nanostructures have been highlighted, including silver-decorated polymer micelles and vesicles, antimicrobial polymer micelles and vesicles, and antimicrobial peptide-based vesicles, etc. Furthermore, we proposed the current challenges and future research directions in the field of antibacterial polymeric nanostructures for the real-world biomedical applications. PMID- 25110922 TI - Early surgery and survival of patients with anaplastic thyroid carcinoma: analysis of a case series referred to a single institution between 1999 and 2012. AB - BACKGROUND: Extensive resection of the tumor has been associated with better survival of anaplastic thyroid carcinoma (ATC) patients. However, surgery is not the rule for ATC patients with distant metastases at the time of diagnosis (stage IV-C), regardless of tumor resectability. The aim of this work was to explore the potential role of surgery in ATC patients, including those in stage IV-C. METHODS: We considered all the consecutive ATC patients referred to our institution from June 1999 to July 2012. Patients with stage IV-A incidentally discovered ATC were excluded because of their better prognosis. All patients eligible for surgery at the time of diagnosis were first operated with the intent to obtain a macroscopically complete resection (R0, R1), or a R2 resection with minimal macroscopical residual tumor. These operations were defined as "maximal debulking," whereas operations that did not achieve this goal were defined as "partial debulking." After surgery, almost all patients received adjuvant chemotherapy, associated to radiotherapy in more than 50% of patients. RESULTS: There were 55 eligible patients (34 women; median age 73.15 years). Thirty-one patients had distant metastases (stage IV-C). The median overall survival was 5.55 months [CI 4.94-6.60], with no difference according to stage. "Maximal debulking" was obtained in 70.73% of operated patients as a first modality and resulted associated with better survival than "partial debulking" (6.57 months [CI 5.52-12.09] vs. 3.25 months [CI 0.66-4.80]), without any difference between stage IV-B and IV-C patients. Furthermore, 21% of patients submitted to "maximal debulking" died secondary to local progression of the tumor, whereas this was the case for 69% of patients treated with "partial debulking" or not operated at all. CONCLUSIONS: Early "maximal debulking," followed by adjuvant therapy, can improve the survival and ameliorate the quality of residual life preventing the risk of suffocation. This effect is also observed in patients with distant metastasis at diagnosis and treated with this approach: they have an outcome similar to that observed in stage IV-B patients. We thus suggest that surgery may be considered in the management of all ATC patients, and should not be restricted a priori to stages IV-A and IV-B. PMID- 25110923 TI - Scope of physician procedures independently billed by mid-level providers in the office setting. AB - IMPORTANCE: Mid-level providers (nurse practitioners and physician assistants) were originally envisioned to provide primary care services in underserved areas. This study details the current scope of independent procedural billing to Medicare of difficult, invasive, and surgical procedures by medical mid-level providers. OBJECTIVE: To understand the scope of independent billing to Medicare for procedures performed by mid-level providers in an outpatient office setting for a calendar year. DESIGN: Analyses of the 2012 Medicare Physician/Supplier Procedure Summary Master File, which reflects fee-for-service claims that were paid by Medicare, for Current Procedural Terminology procedures independently billed by mid-level providers. SETTING AND PARTICIPANTS: Outpatient office setting among health care providers. MAIN OUTCOMES AND MEASURES: The scope of independent billing to Medicare for procedures performed by mid-level providers. RESULTS: In 2012, nurse practitioners and physician assistants billed independently for more than 4 million procedures at our cutoff of 5000 paid claims per procedure. Most (54.8%) of these procedures were performed in the specialty area of dermatology. CONCLUSIONS AND RELEVANCE: The findings of this study are relevant to safety and quality of care. Recently, the shortage of primary care clinicians has prompted discussion of widening the scope of practice for mid-level providers. It would be prudent to temper widening the scope of practice of mid-level providers by recognizing that mid-level providers are not solely limited to primary care, and may involve procedures for which they may not have formal training. PMID- 25110924 TI - Positive changes in self-management and disease severity following climate therapy in people with psoriasis. AB - The aim of this study was to investigate the impact of climate therapy on self management in people with psoriasis. This was a prospective study of 254 adults with chronic psoriasis who participated in a 3-week climate therapy (CT) programme. The 8-scale Health Education Impact Questionnaire (heiQ) was completed at baseline, after 3 weeks of CT, and 3 months later. Change was assessed using paired sample t-tests mean (95% confidence interval) change scores (range 1-4). All heiQ scales showed statistically significant improvement after 3 weeks of CT. The greatest improvement was in Health-directed activity, followed by Emotional distress, and Skill and technique acquisition. At the 3-month follow-up, only the Emotional distress scale remained improved. In addition, disease severity (self administered PASI; SAPASI) improved significantly from before CT to 3 weeks and 3 months after CT. This study suggests that CT provides a range of benefits that are important to people with psoriasis, particularly in the short term. A challenge is how to achieve long-term benefits. PMID- 25110925 TI - Interfacial hydrogenation and deamination of nitriles to selectively synthesize tertiary amines. AB - A novel one-pot method has been developed for the interfacial hydrogenation of nitriles to synthesize asymmetrical tertiary amines. The active Pt NWs allow for the preparation of a series of tertiary amines in excellent yields (up to 99.0%) and a mixed solvent is vital for the adjustment of the yield. And also, the reaction proceeded under mild conditions and is environmentally friendly. PMID- 25110926 TI - Looking for trouble -- patient preference, misdiagnosis and overtesting: a teachable moment. PMID- 25110927 TI - Rapid decline in HCV incidence among people who inject drugs associated with national scale-up in coverage of a combination of harm reduction interventions. AB - BACKGROUND: Government policy has precipitated recent changes in the provision of harm reduction interventions - injecting equipment provision (IEP) and opiate substitution therapy (OST) - for people who inject drugs (PWID) in Scotland. We sought to examine the potential impact of these changes on hepatitis C virus (HCV) transmission among PWID. METHODS AND FINDINGS: We used a framework to triangulate different types of evidence: 'group-level/ecological' and 'individual level'. Evidence was primarily generated from bio-behavioural cross-sectional surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1 2 months) where the virus is present, but antibodies have not yet been formed, were considered to have recent infection. The survey data were supplemented with service data on the provision of injecting equipment and OST. Ecological analyses examined changes in intervention provision, self-reported intervention uptake, self-reported risk behaviour and HCV incidence; individual-level analyses investigated relationships within the pooled survey data. Nearly 8,000 PWID were recruited in the surveys. We observed a decline in HCV incidence, per 100 person years, from 13.6 (95% CI: 8.1-20.1) in 2008-09 to 7.3 (3.0-12.9) in 2011-12; a period during which increases in the coverage of OST and IEP, and decreases in the frequency of injecting and sharing of injecting equipment, were observed. Individual-level evidence demonstrated that combined high coverage of needles/syringes and OST were associated with reduced risk of recent HCV in analyses that were unweighted (AOR 0.29, 95%CI 0.11-0.74) and weighted for frequency of injecting (AORw 0.05, 95%CI 0.01-0.18). We estimate the combination of harm reduction interventions may have averted 1400 new HCV infections during 2008-2012. CONCLUSIONS: This is the first study to demonstrate that impressive reductions in HCV incidence can be achieved among PWID over a relatively short time period through high coverage of a combination of interventions. PMID- 25110929 TI - Influence of California-style black ripe olive processing on the formation of acrylamide. AB - Methods used in processing California-style black ripe olives generate acrylamide. California-style black ripe olives contain higher levels of acrylamide (409.67 +/- 42.60-511.91 +/- 34.08 MUg kg(-1)) as compared to California-style green ripe olives (44.02 +/- 3.55-105.79 +/- 22.01 MUg kg(-1)), Greek olives (<1.42 MUg kg(-1)), and Spanish olives (not detected), indicating that the higher temperatures used to sterilize the California-style green ripe and black ripe olives are required for acrylamide formation. Preprocessing brine storage influenced the formation of acrylamide in a time-dependent manner. Acrylamide increased during the first 30 days of storage. Longer brine storage times (>30 days) result in lower acrylamide levels in the finished product. The presence of calcium ions in the preprocessing brining solution results in higher levels of acrylamide in finished products. Air oxidation during lye processing and the neutralization of olives prior to sterilization significantly increase the formation of acrylamide in the finished products. Conversely, lye-processing decreases the levels of acrylamide in the final product. These results indicate that specific steps in the California-style black ripe olive processing may be manipulated to mitigate the formation of acrylamide in finished products. PMID- 25110928 TI - Comparative analyses between retained introns and constitutively spliced introns in Arabidopsis thaliana using random forest and support vector machine. AB - One of the important modes of pre-mRNA post-transcriptional modification is alternative splicing. Alternative splicing allows creation of many distinct mature mRNA transcripts from a single gene by utilizing different splice sites. In plants like Arabidopsis thaliana, the most common type of alternative splicing is intron retention. Many studies in the past focus on positional distribution of retained introns (RIs) among different genic regions and their expression regulations, while little systematic classification of RIs from constitutively spliced introns (CSIs) has been conducted using machine learning approaches. We used random forest and support vector machine (SVM) with radial basis kernel function (RBF) to differentiate these two types of introns in Arabidopsis. By comparing coordinates of introns of all annotated mRNAs from TAIR10, we obtained our high-quality experimental data. To distinguish RIs from CSIs, We investigated the unique characteristics of RIs in comparison with CSIs and finally extracted 37 quantitative features: local and global nucleotide sequence features of introns, frequent motifs, the signal strength of splice sites, and the similarity between sequences of introns and their flanking regions. We demonstrated that our proposed feature extraction approach was more accurate in effectively classifying RIs from CSIs in comparison with other four approaches. The optimal penalty parameter C and the RBF kernel parameter [Formula: see text] in SVM were set based on particle swarm optimization algorithm (PSOSVM). Our classification performance showed F-Measure of 80.8% (random forest) and 77.4% (PSOSVM). Not only the basic sequence features and positional distribution characteristics of RIs were obtained, but also putative regulatory motifs in intron splicing were predicted based on our feature extraction approach. Clearly, our study will facilitate a better understanding of underlying mechanisms involved in intron retention. PMID- 25110930 TI - Efficacy and safety of adding clopidogrel to aspirin on stroke prevention among high vascular risk patients: a meta-analysis of randomized controlled trials. AB - OBJECTIVES: Whether clopidogrel should be added to aspirin for stroke prevention remained controversial for the risk of hemorrhagic complications. This meta analysis was aimed to assess the efficacy and safety of adding clopidogrel to aspirin on stroke prevention in high vascular risk patients, and to provide evidence for a suitable duration of dual antiplatelet therapy. METHODS: We searched PubMed, EMBase, OVID and Cochrane Central Register of Controlled Trials (up to June, 2013) for randomized controlled trials evaluating the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in high vascular risk patients. Comparisons of stroke and hemorrhagic complications between treatment groups were expressed by the pooled Relative Risks (RRs) with 95% Confidence Intervals (CIs). RESULTS: Fifteen trials with a total of 97692 intention-to-treat participants were included with duration of follow-up ranging from 7 days to 3.6 years. Dual antiplatelet therapy reduced all stroke by 21% (RR: 0.79, 95% CI: 0.73-0.85) with no evidence of heterogeneity across the trials (P = 0.27, I2 = 17%).The effects were consistent between short-term subgroup (<=1 month, RR: 0.76, 95% CI: 0.67-0.85) and long-term subgroup (>=3 months, RR: 0.81, 95% CI: 0.73-0.89). The risk of major bleeding was not significantly increased by dual antiplatelet therapy in short-term subgroup (RR: 1.11, 95% CI: 0.91-1.36), while significantly increased in long-term subgroup (RR: 1.52, 95% CI: 1.36-1.69). Long term dual antiplatelet therapy substantially increased the risk of intracranial bleeding (RR: 1.76, 95% CI: 1.22-2.54). CONCLUSIONS: This meta-analysis demonstrates that short-term combination of clopidogrel and aspirin is effective and safe for stroke prevention in high vascular risk patients. Long-term combination therapy substantially increases the risk of major bleeding and intracranial bleeding. PMID- 25110931 TI - Cognitive deficits predict poorer functional capacity in Huntington's disease: but what is being measured? AB - OBJECTIVE: Huntington's disease (HD) is an inherited movement disorder characterized by choreiform movements and frontostriatal dysfunction. Previous studies have documented executive deficits in HD. We aimed to investigate the effect of cognitive deficits on patients' daily functioning. Furthermore, we sought to explore how independent patients' cognitive difficulties were from their motor and psychiatric symptoms. METHOD: We administered a battery of neuropsychological tasks assessing broader cognitive abilities and executive functions (e.g., verbal fluency, working memory, response inhibition) to 25 patients with HD and 20 healthy controls. Clinical ratings of functional capacity and the severity of motor and psychiatric symptoms were also taken. After establishing that patients with HD demonstrated characteristic cognitive deficits, we explored relationships between performance on neuropsychological tasks and clinical ratings. RESULTS: Patients with HD exhibited deficits on all timed neuropsychological tasks but not on measures of accuracy. Poorer functional capacity was related to cognitive deficits and more severe motor symptoms. Motor and psychiatric symptoms were also related to cognitive performance. Category fluency scores alone predicted 54% of the variance in functional capacity. CONCLUSIONS: Patients with HD exhibited a pattern of cognitive dysfunction that may reflect a generalized slowing in processing. It is important to note that we found that certain cognitive measures may help predict functional capacity in HD. However, we also highlight that performance on neuropsychological tasks can be influenced by motor or psychiatric symptoms. Future studies should consider such confounds when seeking purer measures of cognitive capacity. PMID- 25110932 TI - The role of the occipital face area in holistic processing involved in face detection and discrimination: A tDCS study. AB - OBJECTIVE: The aim of this study was to examine the role of occipital face area (OFA) in mediating observers' tendency to perceive faces as "wholes" (holistic processing) both when detecting and discriminating faces. To investigate this issue, we modulated OFA activity using transcranial direct current stimulation (tDCS). METHOD: In Experiment 1, participants performed a face detection task (the Mooney faces task) and a face discrimination task (the Composite faces task), which both assess holistic face processing. In Experiment 2, participants were asked to detect both Mooney faces and Mooney objects, to test face selectivity of OFA. In each experimental session, the tasks were presented once before (pre) and once after (post) administration of 20 min of excitability increasing anodal tDCS (real) and sham stimulation over the putative OFA. RESULTS: Compared with sham stimulation, we found that real anodal tDCS interfered with both Mooney faces and objects detection, whereas it had no effect on holistic processing involved in face discrimination, as measured by the Composite faces task. CONCLUSIONS: Our results suggest that OFA is causally implicated in facial detection at least in degraded conditions (i.e., when the "face" signal needs to be extracted from a noisy background). In turn, our data do not implicate OFA in holistic processing in face discrimination. Finally, our data suggest a possible role of OFA in categorization of other nonface stimuli, a conclusion that must be taken with caution, as stimulation over OFA may affect object-selective adjacent regions. PMID- 25110935 TI - Recent advances in Charcot-Marie-Tooth disease. AB - PURPOSE OF REVIEW: This article focuses on recent advances in Charcot-Marie-Tooth disease, in particular additions to the genetic spectrum, novel paradigms in molecular techniques and an update on therapeutic strategies. RECENT FINDINGS: Several new Charcot-Marie-Tooth disease-causing genes have been recently identified, further enlarging the genetic diversity and phenotypic variability, including: SBF1, DHTKD1, TFG, MARS, HARS, HINT1, TRIM1, AIFM1, PDK3 and GNB4. The increasing availability and affordability of next-generation sequencing technologies has ramped up gene discovery and drastically changed genetic screening strategies. All large-scale trials studying the effect of ascorbic acid in Charcot-Marie-Tooth 1A have now been completed and were negative. Efforts have been made to design more robust outcome-measures for clinical trials. Promising results with lonaprisan, curcumin and histone deacetylase 6 inhibitors have been obtained in animal models. SUMMARY: Charcot-Marie-Tooth is the most common form of inherited peripheral neuropathy and represents the most prevalent hereditary neuromuscular disorder. The genetic spectrum spans more than 70 genes. Gene discovery has been revolutionized recently by new high-throughput molecular technologies. In addition, the phenotypic diversity has grown tremendously. This is a major challenge for geneticists and neurologists. No effective therapy is available for Charcot-Marie-Tooth. Several large trials with ascorbic acid were negative but research into novel compounds continues. PMID- 25110934 TI - The evidence for symptomatic treatments in amyotrophic lateral sclerosis. AB - PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a progressive, incurable and fatal neurodegenerative disease. Few interventions significantly alter the disease course, but many symptomatic treatments exist to improve patients' quality of life. In this review, we describe our approach to symptomatic management of ALS and discuss the underlying evidence base. RECENT FINDINGS: Discussion focuses predominantly on recently published articles. We cover management settings, disease-modifying treatment, vitamin D, respiratory management including noninvasive ventilation and diaphragmatic pacing, secretions, nutrition, dysphagia and gastrostomy, communication problems, mobility, spasticity, pain, cognition, depression and emotional lability, fatigue, sleep disturbance, head drop, prevention of deep venous thrombosis and end-of-life issues. SUMMARY: Multidisciplinary specialist care appears to improve quality of life and survival. Riluzole remains the only available disease modifying medication and confers a survival advantage of 2-3 months. Noninvasive ventilation improves quality of life and extends survival by approximately 7 months, at least in patients without severe bulbar problems. Nutrition is an independent prognostic factor; whether gastrostomy improves survival and quality of life remains unclear and further studies are underway. Many other symptomatic treatments appear helpful to individuals in clinic, but further randomized clinical trials are required to provide a more robust evidence base. PMID- 25110933 TI - Early life instruction in foreign language and music and incidence of mild cognitive impairment. AB - OBJECTIVE: To test the hypothesis that foreign language and music instruction in early life are associated with lower incidence of mild cognitive impairment (MCI) and slower rate of cognitive decline in old age. METHOD: At enrollment in a longitudinal cohort study, 964 older persons without cognitive impairment estimated years of foreign language and music instruction by age 18. Annually thereafter they completed clinical evaluations that included cognitive testing and clinical classification of MCI. RESULTS: There were 264 persons with no foreign language instruction, 576 with 1-4 years, and 124 with > 4 years; 346 persons with no music instruction, 360 with 1-4 years, and 258 with > 4 years. During a mean of 5.8 years of observation, 396 participants (41.1%) developed MCI. In a proportional hazards model adjusted for age, sex, and education, higher levels (> 4 years) of foreign language (hazard ratio [HR] = 0.687, 95% confidence interval [CI] [0.482, 0.961]) and music (HR = 0.708, 95% CI [0.539, 0.930]) instruction by the age of 18 were each associated with reduced risk of MCI. The association persisted after adjustment for other early life indicators of an enriched cognitive environment, and it was stronger for nonamnestic than amnestic MCI. Both foreign language and music instruction were associated with higher initial level of cognitive function, but neither instruction measure was associated with cognitive decline. CONCLUSIONS: Higher levels of foreign language and music instruction during childhood and adolescence are associated in old age with lower risk of developing MCI but not with rate of cognitive decline. PMID- 25110936 TI - The Effect of a Community-Engaged Arts Program on Older Adults' Well-being. AB - This mixed-methods study evaluated the effect of a community-engaged arts program on the physical, emotional, and social well-being of seniors. Weekly workshops were offered over a three-year period at community centers where artists worked with four groups of seniors to produce a collective art piece or performance for public presentation. Participants completed pre- and post- questionnaires, and group interviews were conducted at the program's end. Paired t-test analyses indicated that seniors experienced improvement in perceived overall health, experience of pain, and sense of community. Interpretive descriptive analysis of the group interviews revealed six themes that informed understanding : (1) providing structure and discipline; (2) facilitating coping; (3) requiring hard work and effort; (4) bringing out one's artistic side; (5) promoting social involvement; and (6) making a contribution. These results are consistent with previous research and contribute to further understanding of how community engaged arts can benefit the well-being of older people. PMID- 25110937 TI - Engineering efficient thermoelectrics from large-scale assemblies of doped ZnO nanowires: nanoscale effects and resonant-level scattering. AB - Recent studies focusing on enhancing the thermoelectric performance of metal oxides were primarily motivated by their low cost, large availability of the component elements in the earth's crust, and their high stability. So far, these studies indicate that n-type materials, such as ZnO, have much lower thermoelectric performance than their p-type counterparts. Overcoming this limitation requires precisely tuning the thermal and electrical transport through n-type metal oxides. One way to accomplish this is through the use of optimally doped bulk assemblies of ZnO nanowires. In this study, the thermoelectric properties of n-type aluminum and gallium dually doped bulk assembles of ZnO nanowires were determined. The results indicated that a high zT of 0.6 at 1000 degrees C, the highest experimentally observed for any n-type oxide, is possible. The high performance is attributed to the tailoring of the ZnO phase composition, nanostructuring of the material, and Zn-III band hybridization-based resonant scattering. PMID- 25110938 TI - A comprehensive global inventory of atmospheric Antimony emissions from anthropogenic activities, 1995-2010. AB - Antimony (Sb) and its compounds are considered as global pollutants due to their health risks and long-range transport characteristics. A comprehensive global inventory of atmospheric antimony emissions from anthropogenic activities during the period of 1995-2010 has been developed with specific estimation methods based on the relevant data available for different continents and countries. Our results indicate that the global antimony emissions have increased to a peak at about 2232 t (t) in 2005 and then declined gradually. Global antimony emissions in 2010 are estimated at about 1904 t (uncertainty of a 95% confidence interval (CI): -30% ~ 67%), with fuel combustion as the major source category. Asia and Europe account for about 57% and 24%, respectively, of the global total emissions, and China, the United States, and Japan rank as the top three emitting countries. Furthermore, global antimony emissions are distributed into gridded cells with a resolution of 1 degrees * 1 degrees . Regions with high Sb emissions are generally concentrated in the Southeastern Asia and Western Europe, while South Africa, economically developed regions in the eastern U.S., and Mexico are also responsible for the high antimony emission intensity. PMID- 25110940 TI - Solving the problem of comparing whole bacterial genomes across different sequencing platforms. AB - Whole genome sequencing (WGS) shows great potential for real-time monitoring and identification of infectious disease outbreaks. However, rapid and reliable comparison of data generated in multiple laboratories and using multiple technologies is essential. So far studies have focused on using one technology because each technology has a systematic bias making integration of data generated from different platforms difficult. We developed two different procedures for identifying variable sites and inferring phylogenies in WGS data across multiple platforms. The methods were evaluated on three bacterial data sets and sequenced on three different platforms (Illumina, 454, Ion Torrent). We show that the methods are able to overcome the systematic biases caused by the sequencers and infer the expected phylogenies. It is concluded that the cause of the success of these new procedures is due to a validation of all informative sites that are included in the analysis. The procedures are available as web tools. PMID- 25110941 TI - Laccase biosensor based on phytic acid modification of nanostructured SiO2 surface for sensitive detection of dopamine. AB - In this work, three kinds of nanostructured silica-phytic acid (SiO2-PA) materials with diverse morphologies including spherical SiO2-PA (s-SiO2-PA), rod like (r-SiO2-PA), and helical SiO2-PA (h-SiO2-PA) were prepared with the help of electrostatic interaction. The SiO2-PA nanomaterials with different morphologies were characterized by using transmission electron microscopy (TEM), Fourier transform infrared (FTIR), electrochemical impedance spectroscopy (EIS), and circular dichroism spectrum (CD). Diverse morphologies of SiO2-PA were used as electrode decorated materials to achieve a high efficiency for electrochemical dopamine (DA) detection. The laccase biosensors were fabricated by immobilizing different morphologies of SiO2-PA nanomaterials and laccase onto the glassy carbon electrode (GCE) surface, successively. Then the electrochemical responses of the different morphologies of nanostructured SiO2-PA nanomaterials to laccase were discussed. Results indicated that compared to laccase/s-SiO2-PA and laccase/r-SiO2-PA, the laccase/h-SiO2-PA-modified electrode showed the best electrochemical performances. PMID- 25110942 TI - Relativistic and electron-correlation effects on the nuclear magnetic resonance shieldings of molecules containing tin and lead atoms. AB - The reference values for NMR magnetic shieldings, sigma(ref), are of the highest importance when theoretical analysis of chemical shifts are envisaged. The fact that the nonrelativistically valid relationship among spin-rotation constants and magnetic shieldings is not any longer valid for heavy atoms requires that the search for sigma(ref) for such atoms needs new strategies to follow. We present here results of sigma(ref) that were obtained by applying our own simple procedure which mixes accurate experimental chemical shifts (delta) and theoretical magnetic shieldings (sigma). We calculated sigma(Sn) and sigma(Pb) in a family of heavy-halogen-containing molecules. We found out that sigma(ref)[Sn;Sn(CH3)4] in gas phase should be close to 3864.11 +/- 20.05 ppm (0.5%). For Pb atom, sigma(ref)[Pb;Pb(CH3)4] should be close to 14475.1 +/- 500.7 ppm. Such theoretical values correspond to calculations with the relativistic polarization propagator method, RelPPA, at the RPA level of approach. They are closer to experimental values as compared to those obtained applying few different functionals such as PBE0, B3LYP, BLYP, BP86, KT2, and KT3 of the density functional theory, DFT. We studied tin and lead shieldings of the XY(4 n)Z(n) (X = Sn, Pb; Y, Z = H, F, Cl, Br, I) and PbH(4-n)I(n) (n = 0, 1, 2, 3, 4) family of compounds with four-component functionals as implemented in the DIRAC code. For these systems results of calculations with RelPPA-RPA are more reliable than DFT ones. We argue about why those DFT functionals must be modified in order to obtain more accurate results of NMR magnetic shieldings within the relativistic regime: first, there is a dependence among both electron-correlation and relativistic effects that should be introduced in some way in the functionals; and second, the DIRAC code uses standard nonrelativistic functionals and the functionals B3LYP and PBE0 were parametrized only with data taken from light elements. It can explain why they are not able to properly introduce relativistic effects on nuclear magnetic shieldings. We finally show that in the analysis of magnetic shieldings for the family of compounds mentioned above, one must consider the newest and so-called heavy-atom effect on vicinal heavy atoms, HAVHA. Such effects are among the most important relativistic effects in these kind of compounds. PMID- 25110943 TI - Synthesis of pyrrolo-/indolo[1,2-a]quinolines and naphtho[2,1-b]thiophenes from gem-dibromovinyls and sulphonamides. AB - A highly efficient and simple route for the synthesis of pyrrolo-/indolo[1,2 a]quinolines and naphtho[2,1-b]thiophenes from gem-dibromovinyls and sulphonamides is reported. The noteworthy feature of this report is that the methodology involves a two-step protocol to synthesize tri- and tetracyclic heterocycles in a one-pot fashion through the Cu(I)-catalyzed formation of ynamide followed by a Ag(I)-assisted intramolecular hydroarylation. The photophysical properties of representative examples of pyrrolo- and indolo[1,2 a]quinolines in solid and solution states have also been studied. PMID- 25110944 TI - Parametrization of 2,2,2-trifluoroethanol based on the generalized AMBER force field provides realistic agreement between experimental and calculated properties of pure liquid as well as water-mixed solutions. AB - We present a novel force field model of 2,2,2-trifluoroethanol (TFE) based on the generalized AMBER force field. The model was exhaustively parametrized to reproduce liquid-state properties of pure TFE, namely, density, enthalpy of vaporization, self-diffusion coefficient, and population of trans and gauche conformers. The model predicts excellently other liquid-state properties such as shear viscosity, thermal expansion coefficient, and isotropic compressibility. The resulting model describes unexpectedly well the state equation of the liquid region in the range of 100 K and 10 MPa. More importantly, the proposed TFE model was optimized for use in combination with the TIP4P/Ew and TIP4P/2005 water models. It does not manifest excessive aggregation, which is known for other models, and therefore, it is supposed to more realistically describe the behavior of TFE/water mixtures. This was demonstrated by means of the Kirkwood-Buff theory of solutions and reasonable agreement with experimental data. We explored a considerable part of the parameter space and systematically tested individual combinations of parameters for performance in combination with the TIP4P/Ew and TIP4P/2005 water models. We observed ambiguity in parameters describing pure liquid TFE; however, most of them failed for TFE/water mixtures. We clearly demonstrated the necessity for balanced TFE-TFE, TFE-water, and water-water interactions which can be acquired only by employing implicit polarization correction in the course of parametrization. PMID- 25110946 TI - Catalytic hydrogen evolution by Fe(II) carbonyls featuring a dithiolate and a chelating phosphine. AB - Two pentacoordinate mononuclear iron carbonyls of the form (bdt)Fe(CO)P2 [bdt = benzene-1,2-dithiolate; P2 = 1,1'-diphenylphosphinoferrocene (1) or methyl-2 {bis(diphenylphosphinomethyl)amino}acetate (2)] were prepared as functional, biomimetic models for the distal iron (Fe(d)) of the active site of [FeFe] hydrogenase. X-ray crystal structures of the complexes reveal that, despite similar nu(CO) stretching band frequencies, the two complexes have different coordination geometries. In X-ray crystal structures, the iron center of 1 is in a distorted trigonal bipyramidal arrangement, and that of 2 is in a distorted square pyramidal geometry. Electrochemical investigation shows that both complexes catalyze electrochemical proton reduction from acetic acid at mild overpotential, 0.17 and 0.38 V for 1 and 2, respectively. Although coordinatively unsaturated, the complexes display only weak, reversible binding affinity toward CO (1 bar). However, ligand centered protonation by the strong acid, HBF4.OEt2, triggers quantitative CO uptake by 1 to form a dicarbonyl analogue [1(H)-CO](+) that can be reversibly converted back to 1 by deprotonation using NEt3. Both crystallographically determined distances within the bdt ligand and density functional theory calculations suggest that the iron centers in both 1 and 2 are partially reduced at the expense of partial oxidation of the bdt ligand. Ligand protonation interrupts this extensive electronic delocalization between the Fe and bdt making 1(H)(+) susceptible to external CO binding. PMID- 25110947 TI - Clearance of intravitreal daptomycin in uveitis-induced rabbit model. AB - PURPOSE: To investigate the elimination rate of daptomycin after intravitreal injection in uveitis-induced rabbits. MATERIALS AND METHODS: Intravitreal injection of the single dose of 200 MUg/0.05 mL daptomycin was administered to rabbits starting 24 h after induction of uveitis by an intravitreal endotoxin injection. Aqueous humor and vitreous humor samples of eight eyes per time point were collected at selected time intervals (1, 3, 6, 24, 48, 72 and 96 h), and the in vitreous half-life was calculated. Daptomycin concentrations in vitreous and aqueous humor were assayed with high-performance liquid chromatography. RESULTS: The vitreous concentration was noted to decline slowly with time. The mean vitreous concentration was 23.25 +/- 10.99 MUg/mL and 11.10 +/- 3.33 MUg/mL at 96 h in inflamed and normal eyes, respectively. The vitreous daptomycin concentration showed an exponential decay with a half-life of 25.67 h in normal eyes and 34.6 h in inflamed eyes. The aqueous levels of daptomycin in normal eyes were low but remained significantly higher than those of inflamed eyes. CONCLUSIONS: Given that the injected dose corresponds to several times the minimum inhibitory concentrations of organisms most involved in endophthalmitis, and that therapeutic levels are present up to 96 h after injection, intravitreal daptomycin should be considered for the treatment of endophthalmitis caused by Gram-positive bacteria. PMID- 25110948 TI - Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida blacktip sharks: guidance for empiric antibiotic therapy. AB - Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (+/-11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (+/ 1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. PMID- 25110949 TI - Anti-human herpesvirus 6A/B IgG correlates with relapses and progression in multiple sclerosis. AB - OBJECTIVE: To analyze the titers of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B) in multiple sclerosis (MS) patients treated with different disease modified therapies (DMTs) along two-years of follow-up. METHODS: We collected 2163 serum samples from 596 MS; for 301 MS patients a 2 years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio). RESULTS: We found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titers reached their highest value two weeks before the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titers reached their highest value one month before the relapse (p = 0.0344). CONCLUSION: The measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results. PMID- 25110951 TI - In silico modeling of human alpha2C-adrenoreceptor interaction with filamin-2. AB - Vascular smooth muscle alpha2C-adrenoceptors (alpha2C-ARs) mediate vasoconstriction of small blood vessels, especially arterioles. Studies of endogenous receptors in human arteriolar smooth muscle cells (referred to as microVSM) and transiently transfected receptors in heterologous HEK293 cells show that the alpha2C-ARs are perinuclear receptors that translocate to the cell surface under cellular stress and elicit a biological response. Recent studies in microVSM unraveled a crucial role of Rap1A-Rho-ROCK-F-actin pathways in receptor translocation, and identified protein-protein interaction of alpha2C-ARs with the actin binding protein filamin-2 as an essential step in the process. To better understand the molecular nature and specificity of this interaction, in this study, we constructed comparative models of human alpha2C-AR and human filamin-2 proteins. Finally, we performed in silico protein-protein docking to provide a structural platform for the investigation of human alpha2C-AR and filamin-2 interactions. We found that electrostatic interactions seem to play a key role in this complex formation which manifests in interactions between the C-terminal arginines of alpha2C-ARs (particularly R454 and R456) and negatively charged residues from filamin-2 region between residues 1979 and 2206. Phylogenetic and sequence analysis showed that these interactions have evolved in warm-blooded animals. PMID- 25110952 TI - The effect of double--blind carbohydrate ingestion during 60 km of self-paced exercise in warm ambient conditions. AB - This study evaluated double blind ingestions of placebo (PLA) versus 6% carbohydrate (CHO) either as capsules (c) or beverage (b) during 60 km self-paced cycling in the heat (32 degrees C and 50% relative humidity). Ten well-trained males (mean +/- SD: 26+/-3 years; 64.5+/-7.7 kg and 70.7+/-8.8 ml.kg-1.min-1 maximal oxygen consumption) completed four separate 60 km time trials (TT) punctuated by 1 km sprints (14, 29, 44, 59 km) whilst ingesting either PLAb or PLAc or CHOb or CHOc. The TT was not different among treatments (PLAb 130.2+/ 11.2 min, CHOb 140.5+/-18.1 min, PLAc 143.1+/-29.2 min, CHOc 137.3+/-20.1 min; P>0.05). Effect size (Cohen's d) for time was only moderate when comparing CHOb - PLAb (d = 0.68) and PLAb - PLAc (d = 0.57) whereas all other ES were 'trivial' to 'small'. Mean speed throughout the trial was significantly higher for PLAb only (P<0.05). Power output was only different (P<0.05) between the sprints and low intensity efforts within and across conditions. Core and mean skin temperatures were similar among trials. We conclude that CHO ingestion is of little or no benefit as a beverage compared with placebo during 60 km TT in the heat. PMID- 25110953 TI - Inhibition of CSF-1R supports T-cell mediated melanoma therapy. AB - Tumor associated macrophages (TAM) can promote angiogenesis, invasiveness and immunosuppression. The cytokine CSF-1 (or M-CSF) is an important factor of TAM recruitment and differentiation and several pharmacological agents targeting the CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We show that the kinase inhibitor PLX3397 strongly dampened the systemic and local accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1(+) myeloid derived suppressor cells. Removal of intratumoral macrophages was remarkably efficient and a modest, but statistically significant, delay in melanoma outgrowth was observed. Importantly, CSF-1R inhibition strongly enhanced tumor control by immunotherapy using tumor-specific CD8 T cells. Elevated IFNgamma production by T cells was observed in mice treated with the combination of PLX3397 and immunotherapy. These results support the combined use of CSF-1R inhibition with CD8 T cell immunotherapy, especially for macrophage-stimulating tumors. PMID- 25110954 TI - Reflections on clinical expertise and silent know-how in voice therapy. AB - The concept of 'clinical expertise' is described as a part of evidence-based practice (EBP) together with 'external scientific evidence' and 'patient values and perspectives'. However, clinical expertise in the management of voice disorders has not been described or discussed in much detail. The expertise seems to consist partly of silent know-how that, from the outside, may seem improperly related to the personality of the speech-language pathologist or exclusively dependent on the number of years in the field. In this paper, it is suggested that clinical expertise in voice therapy consists of specific skills that can be explicitly described and trained. These skills are discussed together with educational aspects that contribute to the development of clinical expertise. The skills are also discussed from the perspectives of the past, present, and future. PMID- 25110955 TI - Unilateral full-thickness macular hole formation following low-energy Nd:YAG peripheral iridotomy. AB - Macular hole formation is a rare complication after YAG peripheral iridotomy. We report a case of post-YAG peripheral iridotomy macular hole in 1 eye of a patient with preexisting vitreomacular adhesion in that eye. Possibly because of the vitreomacular adhesion, a single-shot low-energy YAG laser shot resulted in macular hole formation. PMID- 25110956 TI - Amniotic membrane transplantation in failed trabeculectomy. AB - PURPOSE: To determine the efficacy and safety of amniotic membrane transplantation for trabeculectomy in patients with previous failed filtering blebs. METHODS: A consecutive series of 19 eyes from 18 patients with 1 or more failed trabeculectomies were enrolled in this retrospective study. Trabeculectomy, with amniotic membrane positioned as a "graft" under the scleral flap, was performed, and the intraocular pressure (IOP), number of antiglaucoma medications, appearance of the filtering bleb, and intraoperative and postoperative complication data were retrospectively analyzed for a period of 24 months. Success was defined as IOP<21 mm Hg at the end of the follow-up period. RESULTS: The median preoperative pressure was 29 mm Hg [interquartile range (IQR)=5 mm Hg], with an average of 2.8 glaucoma medications (range, 1 to 4). At 6 months postoperatively the median IOP was 18 mm Hg (IQR=1.75 mm Hg) with no further significant increases recorded, settling at 19 mm Hg (IQR=3.25 mm Hg) at the end of the 24-month follow-up. Success was achieved in all 19 cases (100%), and only 1 patient (5%) required postoperative antiglaucoma therapy to reach the target pressure. At 24 months after surgery, 18 of 19 (95%) amniotic membrane filtering blebs were functioning well without antiglaucoma therapy. No patients had severe intraoperative or postoperative complications. CONCLUSIONS: Amniotic membrane transplantation in trabeculectomy seems to be a safe and useful procedure for improving the surgical outcome and maintaining low postoperative IOP in patients with a high risk of surgical failure. PMID- 25110957 TI - A computational study of the activation of allenoates by Lewis bases and the reactivity of intermediate adducts. AB - Several chemical properties of Lewis base-allenoate adducts (LB.allenoate), such as solvent effect, basicity, nucleophilicity and cycloaddition, are studied to provide a detailed foundation for the analysis of LB-catalyzed reactions of allenoates. The zwitterionic LB.allenoates formed between methyl allenoate and Lewis bases, such as N-heterocyclic carbenes (NHCs), phosphines, amines and aza heterocycles, are studied at the M06-2X/6-31+G* level. The addition of the LBs to the allenoate can yield Z- or E-type adducts. The formation of the Z-type adducts is more favorable in the gas phase due to electrostatic interactions. The yield of the E-type adducts increases with the permittivity of the solvent. The lowest barriers for the addition and the most stable adducts are observed with NHCs as catalysts. It is also shown that the alpha-carbon atom of the allenic moiety in LB.allenoate is more nucleophilic than the gamma-carbon atom. Aza-arenes, phosphines and NHCs stabilize the [3 + 2]-ylides formed by the cycloaddition of LB.allenoate to ethylene; therefore, these LBs thermodynamically support the [3 + 2] cycloadditions. The detailed analysis of [3 + 2]-, [2 + 4]-, [2 + 2]- and [2 + 2 + 2]-cycloadditions with enones/ketones shows that the amine-catalyzed reactions follow the kinetically preferred path, and that the exergonic formation of the P-ylide favors the [3 + 2] cycloaddition in the phosphine-catalyzed reaction. The thermodynamically preferred pathway is followed with NHCs whereas the high stability of NHC.allenoate adducts reduces the overall catalytic efficiency of NHCs. PMID- 25110959 TI - Theoretical and experimental investigations of the potential of osmotic energy for power production. AB - This paper presents a study on the potential of osmotic energy for power production. The study includes both pilot plant testing and theoretical modelling as well as cost estimation. A projected cost of L30/MWh of clean electricity could be achieved by using a Hydro-Osmotic Power (HOP) plant if a suitable membrane is used and the osmotic potential difference between the two solutions is greater than 25 bar; a condition that can be readily found in many sites around the world. Results have shown that the membrane system accounts for 50% 80% of the HOP plant cost depending on the salinity difference level. Thus, further development in membrane technology and identifying suitable membranes would have a significant impact on the feasibility of the process and the route to market. As the membrane permeability determines the HOP process feasibility, this paper also describes the effect of the interaction between the fluid and the membrane on the system permeability. It has been shown that both the fluid physical properties as well as the membrane micro-structural parameters need to be considered if further development of the HOP process is to be achieved. PMID- 25110958 TI - Sex-Related Alcohol Expectancies Among African American Women Attending an Urban STI Clinic. AB - African American women are disproportionately affected by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and sexually transmitted infections (STIs). Alcohol use is a significant risk factor for HIV/STI acquisition. Sex-related alcohol expectancies (SRAEs) may partially account for alcohol-related risky sexual behaviors. Using qualitative interviews we explored the link between alcohol use and risky sex among 20 African American women attending an STI clinic who had consumed four or more alcoholic drinks per drinking day (binge drinking) and/or reported vaginal or anal sex while under the influence of alcohol. Four SRAEs emerged, which we named drink for sexual desire, drink for sexual power, drink for sexual excuse, and drink for anal sex. While the desire SRAE has been documented, this study identified three additional SRAEs not currently assessed by expectancy questionnaires. These SRAEs may contribute to high-risk sex when under the influence of alcohol and suggests the importance of developing integrated alcohol-sexual risk reduction interventions for high risk women. PMID- 25110961 TI - Isolation and characterization of glycophorin from carp red blood cell membranes. AB - We isolated a high-purity carp glycophorin from carp erythrocyte membranes following extraction using the lithium diiodosalicylate (LIS)-phenol method and streptomycin treatment. The main carp glycophorin was observed to locate at the position of the carp and human band-3 proteins on an SDS-polyacrylamide gel. Only the N-glycolylneuraminic acid (NeuGc) form of sialic acid was detected in the carp glycophorin. The oligosaccharide fraction was separated into two components (P-1 and P-2) using a Glyco-Pak DEAE column. We observed bacteriostatic activity against five strains of bacteria, including two known fish pathogens. Fractions from the carp erythrocyte membrane, the glycophorin oligosaccharide and the P-1 also exhibited bacteriostatic activity; whereas the glycolipid fraction and the glycophorin fraction without sialic acid did not show the activity. The carp glycophorin molecules attach to the flagellum of V. anguillarum or the cell surface of M. luteus and inhibited bacterial growth. PMID- 25110960 TI - Auxiliary subunits: shepherding AMPA receptors to the plasma membrane. AB - Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated cation channels that mediate excitatory signal transmission in the central nervous system (CNS) of vertebrates. The members of the iGluR subfamily of alpha-amino-3 hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate most of the fast excitatory signal transmission, and their abundance in the postsynaptic membrane is a major determinant of the strength of excitatory synapses. Therefore, regulation of AMPAR trafficking to the postsynaptic membrane is an important constituent of mechanisms involved in learning and memory formation, such as long-term potentiation (LTP) and long-term depression (LTD). Auxiliary subunits play a critical role in the facilitation and regulation of AMPAR trafficking and function. The currently identified auxiliary subunits of AMPARs are transmembrane AMPA receptor regulatory proteins (TARPs), suppressor of lurcher (SOL), cornichon homologues (CNIHs), synapse differentiation-induced gene I (SynDIG I), cysteine-knot AMPAR modulating proteins 44 (CKAMP44), and germ cell specific gene 1-like (GSG1L) protein. In this review we summarize our current knowledge of the modulatory influence exerted by these important but still underappreciated proteins. PMID- 25110962 TI - Serum oxidative stress, visfatin and apelin in healthy women and those with premenstrual syndrome. AB - The aim of this study was to investigate whether there is a relationship between premenstrual syndrome and oxidative stress, visfatin and apelin. The study included 40 women with premenstrual syndrome and 40 healthy women. In all subjects, serum visfatin, apelin and oxidative stress parameters were studied in venous blood samples. The oxidative stress parameters were higher in the premenstrual syndrome group than among the controls, but this difference did not reach statistical significance (p > 0.05). It was found that total antioxidant capacity was similar in both groups. For the insulin-serotonin cycle markers, no significant difference was found between groups in terms of visfatin level (p = 0.893), although apelin was found to be significantly higher in the premenstrual syndrome group when compared with the controls (p < 0.001). According to our results, apelin can be used as an ancillary laboratory test in the diagnosis of premenstrual syndrome. PMID- 25110963 TI - Understanding spatial relationships in US: a computer-based training tool that utilizes inexpensive off-the-shelf game controllers. AB - The authors present a simulation-based ultrasonographic (US) training tool that can help improve the understanding of spatial relationships in US. Use of a game controller to simulate a US probe allows examination of different virtual three dimensional (3D) objects. These 3D objects are either completely artificial simple geometric objects (eg, spheres, tubes, and ellipsoids, or more complex combinations thereof) or derived from photographed gross anatomic data (eg, the Visible Human dataset [U.S. National Library of Medicine]) or clinical computed tomographic (CT) data. The virtual US probe allows infinitely variable real-time positioning of a "slice" that is displayed as a two-dimensional (2D) cross sectional image and as part of a 3D view. Combining the 2D and 3D views helps elucidate the spatial relationships between a 3D object and derived 2D images. This training tool provides reliable real-time interactivity and is widely available and easily affordable, since it utilizes standard personal computer technology and off-the-shelf gaming hardware. For instance, it can be used at home by medical students or residents as a complement to conventional US training. In the future, this system could be adapted to support training for US guided needle biopsy, with use of a second game controller to control the biopsy needle. Furthermore, it could be used as a more general interactive visualization tool for the evaluation of clinical 3D CT and magnetic resonance imaging data, allowing efficient and intuitive real-time creation of oblique multiplanar reformatted images. PMID- 25110964 TI - New open-framework cobalt sulfate-oxalates based on molecular and chain-like building blocks. AB - Presented here are two novel open-framework cobalt sulfate-oxalates constructed from molecular and chain-like building blocks. The two compounds have different structures: an hcb-type layer with 20-ring windows and a mog-type framework with 12-ring channels. Amine molecules play dual roles in the two structures: as a chelating ligand and a charge-balancing agent. PMID- 25110965 TI - Short stories on zebrafish long noncoding RNAs. AB - The recent re-annotation of the transcriptome of human and other model organisms, using next-generation sequencing approaches, has unravelled a hitherto unknown repertoire of transcripts that do not have a potential to code for proteins. These transcripts have been largely classified into an amorphous class popularly known as long noncoding RNAs (lncRNA). This discovery of lncRNAs in human and other model systems have added a new layer to the understanding of gene regulation at the transcriptional and post-transcriptional levels. In recent years, three independent studies have discovered a number of lncRNAs expressed in different stages of zebrafish development and adult tissues using a high throughput RNA sequencing approach, significantly adding to the repertoire of genes known in zebrafish. A subset of these transcripts also shows distinct and specific spatiotemporal patterns of gene expression, pointing to a tight regulatory control and potential functional roles in development, organogenesis, and/ or homeostasis. This review provides an overview of the lncRNAs in zebrafish and discusses how their discovery could provide new insights into understanding biology, explaining mutant phenotypes, and helping in potentially modeling disease processes. PMID- 25110967 TI - Serotherapy for Ebola: back to the future. PMID- 25110968 TI - Hidden victims of childhood vitiligo: impact on parents' mental health and quality of life. AB - This study aims to assess the impact of childhood vitiligo on the psychological status and quality of life of their parents, and to determine how this varies according to their children's disease condition. The study included 50 families of children with vitiligo (a total of 75 participants) and 50 families of normal children (a total of 79 participants). The psychosocial impact of the disease on parents was measured using the Self-rated Health Measurement Scale (SRHMS) and the Dermatitis Family Impact Questionnaire (DFI). SRHMS scores for parents of children with vitiligo were significantly lower than for parents with normal children. In addition, women had lower scores than men in the study group. The mean DFI score in affected families was higher than in unaffected families. Parents of children with vitiligo have significant psychological problems, and their quality of life is poorer than for parents of normal children. In conclusion, parents of children with vitiligo need as much care and attention as their affected children. PMID- 25110969 TI - Routine blood cultures for the febrile inpatient: a teachable moment. PMID- 25110966 TI - Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. AB - IMPORTANCE: Disorders of brain metabolism are multiform in their mechanisms and manifestations, many of which remain insufficiently understood and are thus similarly treated. Glucose transporter type I deficiency (G1D) is commonly associated with seizures and with electrographic spike-waves. The G1D syndrome has long been attributed to energy (ie, adenosine triphosphate synthetic) failure such as that consequent to tricarboxylic acid (TCA) cycle intermediate depletion. Indeed, glucose and other substrates generate TCAs via anaplerosis. However, TCAs are preserved in murine G1D, rendering energy-failure inferences premature and suggesting a different hypothesis, also grounded on our work, that consumption of alternate TCA precursors is stimulated and may be detrimental. Second, common ketogenic diets lead to a therapeutically counterintuitive reduction in blood glucose available to the G1D brain and prove ineffective in one-third of patients. OBJECTIVE: To identify the most helpful outcomes for treatment evaluation and to uphold (rather than diminish) blood glucose concentration and stimulate the TCA cycle, including anaplerosis, in G1D using the medium-chain, food-grade triglyceride triheptanoin. DESIGN, SETTING, AND PARTICIPANTS: Unsponsored, open-label cases series conducted in an academic setting. Fourteen children and adults with G1D who were not receiving a ketogenic diet were selected on a first-come, first-enrolled basis. INTERVENTION: Supplementation of the regular diet with food-grade triheptanoin. MAIN OUTCOMES AND MEASURES: First, we show that, regardless of electroencephalographic spike-waves, most seizures are rarely visible, such that perceptions by patients or others are inadequate for treatment evaluation. Thus, we used quantitative electroencephalographic, neuropsychological, blood analytical, and magnetic resonance imaging cerebral metabolic rate measurements. RESULTS: One participant (7%) did not manifest spike waves; however, spike-waves promptly decreased by 70% (P = .001) in the other participants after consumption of triheptanoin. In addition, the neuropsychological performance and cerebral metabolic rate increased in most patients. Eleven patients (78%) had no adverse effects after prolonged use of triheptanoin. Three patients (21%) experienced gastrointestinal symptoms, and 1 (7%) discontinued the use of triheptanoin. CONCLUSIONS AND RELEVANCE: Triheptanoin can favorably influence cardinal aspects of neural function in G1D. In addition, our outcome measures constitute an important framework for the evaluation of therapies for encephalopathies associated with impaired intermediary metabolism. PMID- 25110970 TI - Tunable exciton funnel using Moire superlattice in twisted van der Waals bilayer. AB - A spatially varying bandgap drives exciton motion and can be used to funnel energy within a solid (Nat. Photonics 2012, 6, 866-872). This bandgap modulation can be created by composition variation (traditional heterojunction), elastic strain, or in the work shown next, by a small twist between two identical semiconducting atomic sheets, creating an internal stacking translation u(r) that varies gently with position r and controls the local bandgap Eg(u(r)). Recently synthesized carbon/boron nitride (Nat. Nanotechnol. 2013, 8, 119) and phosphorene (Nat. Nanotechnol. 2014, 9, 372) may be used to construct this twisted semiconductor bilayer that may be regarded as an in-plane crystal but an out-of plane molecule, which could be useful in solar energy harvesting and electroluminescence. Here, by first-principles methods, we compute the bandgap map and delineate its material and geometric sensitivities. Eg(u(r)) is predicted to have multiple local minima ("funnel centers") due to secondary or even tertiary periodic structures in-plane, leading to a hitherto unreported pattern of multiple "exciton flow basins". A compressive strain or electric field will further enhance Eg-contrast in different regions of the pseudoheterostructure so as to absorb or emit even broader spectrum of light. PMID- 25110971 TI - Biofunctional constituent isolated from Citrullus colocynthis fruits and structure-activity relationships of its analogues show acaricidal and insecticidal efficacy. AB - The acaricidal and insecticidal potential of the active constituent isolated from Citrullus colocynthis fruits and its structurally related analogues was evaluated by performing leaf disk, contact toxicity, and fumigant toxicity bioassays against Tetranychus urticae, Sitophilus oryzae, and Sitophilus zeamais adults. The active constituent of C. colocynthis fruits was isolated by chromatographic techniques and was identified as 4-methylquinoline on the basis of spectroscopic analyses. To investigate the structure-activity relationships, 4-methylquinoline and its structural analogues were tested against mites and two insect pests. On the basis of the LC50 values, 7,8-benzoquinoline was the most effective against T. urticae. Quinoline, 8-hydroxyquinoline, 2-methylquinoline, 4-methylquinoline, 6-methylquinoline, 8-methylquinoline, and 7,8-benzoquinoline showed high insecticidal activities against S. oryzae and S. zeamais regardless of the application method. These results indicate that introduction of a functional group into the quinoline skeleton and changing the position of the group have an important influence on the acaricidal and insecticidal activities. Furthermore, 4 methylquinoline isolated from C. colocynthis fruits, along with its structural analogues, could be effective natural pesticides for managing spider mites and stored grain weevils. PMID- 25110972 TI - The psychosocial impact of detention and deportation on U.S. migrant children and families. AB - Approximately 4.5 million U.S. citizen children live in mixed-status families, in which at least 1 family member is an unauthorized migrant and therefore vulnerable to detention and deportation from the United States (Passel & Cohn, 2011). This article critically examines the current state of the literature on the psychosocial consequences of detention and deportation for unauthorized migrants, mixed-status families, and their U.S.-born children. In particular, drawing on social and psychological theory and research, we (a) review the impact of parents' unauthorized status on children; (b) summarize the literature on the impact of detention processes on psychosocial well-being; (c) describe the dilemma faced by a mixed-status family when a parent faces deportation; (d) examine the current social scientific literature on how parental deportation impacts children and their families; and (e) summarize several policy recommendations for protecting children and families. PMID- 25110973 TI - Posttraumatic growth in children and youth: clinical implications of an emerging research literature. AB - Posttraumatic growth (PTG), positive change resulting from the struggle with trauma, has garnered significant attention in the literature on adults. Recently, the research base has begun to extend downward, and this literature indicates that youth also evidence PTG-like changes. Researchers have sought to assess the construct, examine its correlates, and understand the factors that contribute to PTG in youth. Drawing from this work, this article considers clinical implications for youth. After briefly describing the PTG construct, its hypothesized process, and its distinction from resilience, the article focuses on key themes in the literature and, with those findings as backdrop, ways in which professionals can facilitate growth in youth who have experienced trauma. This discussion situates PTG within the broader trauma literature and includes specific applications used to date as well as the role of cultural factors. Future directions--salient to practitioners and researchers alike--are considered. PMID- 25110974 TI - Sudden losses and negative appraisal in people with severe mental illness. AB - Research on the impact of sudden or unexpected losses in people with severe mental illness is scarce. The purpose of our study was to examine the relationship between subjective distress from sudden losses in people with severe mental illness and posttraumatic stress symptoms while controlling for gender, psychiatric symptoms, and negative appraisals. As part of routine care, treatment personnel collected data from 371 community mental health clients diagnosed with a severe mental illness. Hierarchical linear regression revealed that negative appraisals of the self and the world correlated significantly with posttraumatic stress symptoms, and distress from losses accounted for the greatest amount of variance in posttraumatic stress symptoms of the 6 traumas tested. When examined by diagnostic group, only those with schizophrenia spectrum disorder showed a significant association between distress from sudden losses and posttraumatic stress symptoms. Relative to other factors including symptoms of severe mental illness, distress from sudden losses in people with severe mental illness appears to be strongly associated with posttraumatic stress symptoms. PMID- 25110975 TI - Contemporary heterosexism on campus and psychological distress among LGBQ students: the mediating role of self-acceptance. AB - Contemporary heterosexism includes both overt and subtle discrimination. Minority stress theory posits that heterosexism puts sexual minorities at risk for psychological distress and other negative outcomes. Research, however, tends to focus only on 1 form at a time, with minimal attention being given to subtle heterosexism. Further, little is known about the connection between minority stressors and underlying psychological mechanisms that might shape mental health outcomes. Among a convenience sample of lesbian, gay, bisexual, and queer (LGBQ) college students (n = 299), we investigated the role of blatant victimization and LGBQ microaggressions, both together and separately, on psychological distress and the mediating role of self-acceptance. We conducted structural equation modeling to examine hypothesized relationships. Heterosexism was measured as blatant victimization, interpersonal microaggressions, and environmental microaggressions. Self-acceptance included self-esteem and internalized LGBTQ pride. Anxiety and perceived stress comprised the psychological distress factor. Our results suggest that students with greater atypical gender expression experience, greater overall heterosexism and victimization, and younger students experience more overall heterosexism, and undergraduates report more victimization. Microaggressions, particularly environmental microaggressions, are more influential on overall heterosexism than blatant victimization. Overall heterosexism and microaggressions demonstrated main effects with self-acceptance and distress, whereas victimization did not. Self-acceptance mediated the path from discrimination to distress for both overall heterosexism and microaggressions. Our findings advance minority stress theory research by providing a nuanced understanding of the nature of contemporary discrimination and its consequences, as well as illuminating the important role self-acceptance plays as a mediator in the discrimination-psychological distress relationship. PMID- 25110976 TI - Risk factors for suicidal behaviors among Filipino Americans: a data mining approach. AB - Filipino Americans have lower suicide rates than other Asian ethnic groups. The present study examined risk factors for suicide ideation and attempt among Filipino Americans with random forest. The data were from the Filipino American Community Epidemiological Study (Takeuchi, 2011). The results showed that the important predictors for suicide ideation were depressive disorder, substance use disorder, and years in the United States. The important predictors for suicide attempt were the number of family relatives and family conflict. Clinicians are advised to investigate familial and cultural factors among Filipino Americans. How family and cultural factors may affect suicidal behaviors were further discussed. PMID- 25110977 TI - Menstrual suppression for adolescents. AB - PURPOSE OF REVIEW: The purpose of this review is to highlight the recent literature and emerging data describing clinical situations in which menstrual suppression may improve symptoms and quality of life for adolescents. A variety of conditions occurring frequently in adolescents and young adults, including heavy menstrual bleeding, and dysmenorrhea as well as gynecologic conditions such as endometriosis and pelvic pain, can safely be improved or alleviated with appropriate menstrual management. RECENT FINDINGS: Recent publications have highlighted the efficacy and benefit of extended cycle or continuous combined oral contraceptives, the levonorgestrel intrauterine device, and progestin therapies for a variety of medical conditions. SUMMARY: This review places menstrual suppression in an historical context, summarizes methods of hormonal therapy that can suppress menses, and reviews clinical conditions for which menstrual suppression may be helpful. PMID- 25110978 TI - Risk factors for urinary, fecal, or double incontinence in women. AB - PURPOSE OF REVIEW: To review recent, significant contributions to the medical literature regarding the identification of factors which are associated with urinary, fecal, and double incontinence in women. RECENT FINDINGS: Approximately one out of five women suffers from moderate to severe urinary incontinence, one out of 10 has fecal incontinence, and 2.5% have double incontinence of urine and stool. Obesity is primarily associated with urinary incontinence, whereas diabetes mellitus is a stronger risk factor for fecal incontinence. Double incontinence is primarily associated with advanced age, depression, and decompensating medical conditions that denote frailty. SUMMARY: Knowledge regarding which clinical conditions and patient characteristics are strongly associated with each type of incontinence helps identify those patients who are at risk and aids in targeted screening and treatment programs. PMID- 25110979 TI - Multidisciplinary care for individuals with disorders of sex development. AB - PURPOSE OF REVIEW: Recommendations regarding the care of individuals with disorders of sex development include that care be provided by multidisciplinary teams. This article will discuss team composition and function as well as the role of the gynecologist and barriers to such care. RECENT FINDINGS: Many barriers to multidisciplinary care exist, but recent reports stress the roles of different team members as well as tools for planning and implementation of such a team that may help to overcome such barriers. All current recommendations include the participation of a gynecologist in the disorders of sex development team. Gynecologists are in the unique position to continue to provide care as these individuals mature into adulthood. SUMMARY: Multidisciplinary care for patients with disorders of sex development is recommended and gynecologists provide unique expertise. PMID- 25110980 TI - Uncovering the Meaning of Home Care Using an Arts-Based and Qualitative Approach. AB - The need for home care is increasing in Canada, yet little is known about the home care experience of clients and their families. Uncovering the meaning of the home care experience is an important step towards developing understanding and public awareness. We explored the experiences of home care using arts-based methods and individual interviews with 11 participants (one client and 10 family caregivers). Participants discussed the numerous ways formal home care and family caregiving affected their lives, how they coped with these effects, their experiences in hospitals or assisted living facilities, and aspects of the home care experience they liked or disliked. Participants agreed that home care facilitated a better quality of life for families and clients, although they acknowledged some challenges with it. The artistic outputs produced by participants facilitated interview dialogue and fostered understanding of key themes within the research team. PMID- 25110981 TI - Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis. AB - INTRODUCTION: The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti-inflammatory pathway reduced disease severity in the collagen-induced arthritis model. METHODS: Rats implanted with vagus nerve cuff electrodes had collagen-induced arthritis induced and were followed for 15 days. Animals underwent active or sham electrical stimulation once daily from day 9 through the conclusion of the study. Joint swelling, histology, and levels of cytokines and bone metabolism mediators were assessed. RESULTS: Compared with sham treatment, active neurostimulation of the cholinergic anti-inflammatory pathway resulted in a 52% reduction in ankle diameter (p = 0.02), a 57% reduction in ankle diameter (area under curve; p = 0.02) and 46% reduction overall histological arthritis score (p = 0.01) with significant improvements in inflammation, pannus formation, cartilage destruction, and bone erosion (p = 0.02), accompanied by numerical reductions in systemic cytokine levels, not reaching statistical significance. Bone erosion improvement was associated with a decrease in serum levels of receptor activator of NF-kappaB ligand (RANKL) from 132+/-13 to 6+/-2 pg/mL (mean+/-SEM, p = 0.01). CONCLUSIONS: The severity of collagen-induced arthritis is reduced by neurostimulation of the cholinergic anti-inflammatory pathway delivered using an implanted electrical vagus nerve stimulation cuff electrode, and supports the rationale for testing this approach in human inflammatory disorders. PMID- 25110982 TI - Association between duration of carbon dioxide pneumoperitoneum during laparoscopic abdominal surgery and hepatic injury: a meta-analysis. AB - BACKGROUND: The aim of this study is to accurately assess whether the duration of intraoperative carbon dioxide pneumoperitoneum (CDP) is associated with the induction of hepatic injury. METHODS: We conducted a systematic review of PubMed, Embase, and Cochrane Library databases (through February 2014) to identify case match studies that compared high-pressure CDP with low-pressure CDP or varied the duration of CDP in patients who underwent abdominal surgery. The outcome of interest was postoperative liver function (ALT, AST, TB). RESULTS: Eleven comparative studies involving 2,235 participants were included. Overall, levels of ALT, AST, and TB (on postoperative days 1, 3, and 7) were significantly elevated in the study groups. However, the results of the subanalyses of those who underwent laparoscopic colorectal cancer resection (LCR) versus open colorectal cancer resection (OCR) and those who underwent laparoscopic gastric bypass (LGBP) versus open gastric bypass (OGBP) were inconsistent. CONCLUSIONS: The current evidence suggests that the duration of CDP during laparoscopic abdominal surgery may be associated with hepatic injury. Additional large-scale, randomized, controlled trials are urgently needed to further confirm this. PMID- 25110983 TI - Bioaccumulation and toxicity of CuO nanoparticles by a freshwater invertebrate after waterborne and dietborne exposures. AB - The incidental ingestion of engineered nanoparticles (NPs) can be an important route of uptake for aquatic organisms. Yet, knowledge of dietary bioavailability and toxicity of NPs is scarce. Here we used isotopically modified copper oxide ((65)CuO) NPs to characterize the processes governing their bioaccumulation in a freshwater snail after waterborne and dietborne exposures. Lymnaea stagnalis efficiently accumulated (65)Cu after aqueous and dietary exposures to (65)CuO NPs. Cu assimilation efficiency and feeding rates averaged 83% and 0.61 g g(-1) d(-1) at low exposure concentrations (<100 nmol g(-1)), and declined by nearly 50% above this concentration. We estimated that 80-90% of the bioaccumulated (65)Cu concentration in L. stagnalis originated from the (65)CuO NPs, suggesting that dissolution had a negligible influence on Cu uptake from the NPs under our experimental conditions. The physiological loss of (65)Cu incorporated into tissues after exposures to (65)CuO NPs was rapid over the first days of depuration and not detectable thereafter. As a result, large Cu body concentrations are expected in L. stagnalis after exposure to CuO NPs. To the degree that there is a link between bioaccumulation and toxicity, dietborne exposures to CuO NPs are likely to elicit adverse effects more readily than waterborne exposures. PMID- 25110984 TI - Self-assembly of a tripeptide into a functional coating that resists fouling. AB - This communication describes the self-assembly of a tripeptide into a functional coating that resists biofouling. Using this peptide-based coating we were able to prevent protein adsorption and interrupt biofilm formation. This coating can be applied on numerous substrates and therefore can serve in applications related to health care, marine and water treatment. PMID- 25110985 TI - Relationships Among Meeting Physical-Activity Guidelines and Health Risk Behaviors. AB - BACKGROUND: Young adults have the highest participation in physical activity but also have the highest incidence rates of binge drinking, cigarette smoking, and smokeless tobacco use. We examined these factors to determine whether there are relationships among physical activity and health risk behaviors. METHODS: We conducted correlation and chi2 analyses using the American College Health Association-National College Health Assessment fall 2009 data set (N = 34,208) to examine the relationship among meeting physical-activity guidelines, binge drinking, and tobacco use among survey participants. RESULTS: The data suggest a positive relationship between meeting physical-activity guidelines and binge drinking, with the strongest relationship between those reporting binge drinking 4 times in a 2-week period. Meeting physical-activity guidelines was negatively associated with cigarette use but positively associated with all other types of tobacco use. CONCLUSIONS: Associations between physical activity and binge drinking episodes indicate a need to address the relationship between heavy drinking and alcohol dependence and physical-activity behavior patterns. Further studies should examine relationships between physical activity and binge drinking in other age groups. Results also suggest the need to examine differing associations between physical activity and types of tobacco use. PMID- 25110987 TI - Dendrimersomes with photodegradable membranes for triggered release of hydrophilic and hydrophobic cargo. AB - Amphiphilic Janus dendrimers containing first through third generation (G1-G3) photodegradable hydrophobic blocks were synthesized and their self-assembly in water was studied. While the G1 and G2 systems formed solid aggregates, the G3 system self-assembled to form dendrimersomes. These dendrimersomes were demonstrated to degrade upon irradiation with UV light, and exhibited triggered release of both hydrophobic and hydrophilic payloads. PMID- 25110986 TI - On simplified global nonlinear function for fitness landscape: a case study of inverse protein folding. AB - The construction of fitness landscape has broad implication in understanding molecular evolution, cellular epigenetic state, and protein structures. We studied the problem of constructing fitness landscape of inverse protein folding or protein design, with the aim to generate amino acid sequences that would fold into an a priori determined structural fold which would enable engineering novel or enhanced biochemistry. For this task, an effective fitness function should allow identification of correct sequences that would fold into the desired structure. In this study, we showed that nonlinear fitness function for protein design can be constructed using a rectangular kernel with a basis set of proteins and decoys chosen a priori. The full landscape for a large number of protein folds can be captured using only 480 native proteins and 3,200 non-protein decoys via a finite Newton method. A blind test of a simplified version of fitness function for sequence design was carried out to discriminate simultaneously 428 native sequences not homologous to any training proteins from 11 million challenging protein-like decoys. This simplified function correctly classified 408 native sequences (20 misclassifications, 95% correct rate), which outperforms several other statistical linear scoring function and optimized linear function. Our results further suggested that for the task of global sequence design of 428 selected proteins, the search space of protein shape and sequence can be effectively parametrized with just about 3,680 carefully chosen basis set of proteins and decoys, and we showed in addition that the overall landscape is not overly sensitive to the specific choice of this set. Our results can be generalized to construct other types of fitness landscape. PMID- 25110988 TI - Behavior of highly diluted electrolytes in strong electric fields-prevention of alumina deposition on grading electrodes in HVDC transmission modules by CO2 induced pH-control. AB - Alumina deposition on platinum grading electrodes in high voltage direct current (HVDC) transmission modules is an unsolved problem that has been around for more than three decades. This is due to the unavoidable corrosion of aluminum heat sinks that causes severe damage to electrical power plants and losses in the range of a million Euro range per day in power outage. Simple experiments in a representative HV test setup showed that aluminates at concentrations even below 10(-8) mol L(-1) can deposit on anodes through neutralization by protons produced in de-ionized water (kappa<=0.15 MUS cm(-1)) at 20-35 kV (8 mA) per electrode. In this otherwise electrolyte-poor aqueous environment, the depositions are formed three orders of magnitude below the critical precipitation concentration at pH 7! In the presence of an inert electrolyte such as TMAT (tetramethylammonium-p toluenesulfonate), at a concentration level just above that of the total dissolved aluminum, no deposition was observed. Deposition can be also prevented by doping with CO2 gas at a concentration level that is magnitudes lower than that of the dissolved aluminum. From an overview of aqueous aluminum chemistry, the mystery of the alumina deposition process and its inhibition by CO2 is experimentally resolved and fully explained by field accumulation and repulsion models in synergism with acid-base equilibria. The extraordinary size of the alumina depositions is accounted for in terms of proton tunneling through "hydrated" alumina, which is supported by quantum chemical calculations. As a consequence, pulse-purging with pure CO2 gas is presented as a technical solution to prevent the deposition of alumina. PMID- 25110989 TI - Measuring the pK/pI of biomolecules using X-ray photoelectron spectroscopy. AB - Dissociation constants of GG-X-GG and X5 peptides (X = G, D, H, or K), and bovine albumin (BSA) and fibronectin (FN) were measured by X-ray photoelectron spectroscopy (XPS) in ultrahigh vacuum at room temperature. The biomolecules were deposited on Au substrates by drying 2.0 MUL drops of 1.0 MUg MUL(-1) stock solutions in 100 mM sodium phosphate buffers (pH 1-12) at room temperature. Because of the ~+1.3 eV shift in binding energy (BE) of protonated amines, pK values of basic amino acids were calculated by plotting the fraction of protonated amines as a function of solution pH. Similarly, the BE of carboxyl groups shifted ~-1.3 eV upon deprotonation. While C 1s spectra were convoluted by the multiple chemical states of carbon present in the samples, the ratio of the C 1s components centered at BE = 289.0 +/- 0.4 and BE = 287.9 +/- 0.3 proved to reliably assess deprotonation of carboxyl groups. The pK values for the Asp (3.1 and 2.4), His (6.7), and Lys (11.3 and 10.6) peptides, and the pI of BSA (4.8) and FN (5.7), were consistent with published values; thus, these methods could potentially be used to determine the dissociation constants of surface-bound biomolecules. PMID- 25110990 TI - A normal ovary in an abnormal location: A case of torsion. AB - The clinical and radiologic diagnosis of adnexal torsion is challenging. The patient's history, physical examination, and laboratory evaluation may overlap significantly with other causes of abdominal pain. Ultrasound is the most common radiologic tool to assess for torsion, and the imaging findings can be equally equivocal. We present a case of adnexal torsion in an 18-year-old emergency room patient with abdominal pain, diagnosed by ultrasound based solely on an abnormal medial position of the ovary-a finding that has been only rarely mentioned in the literature, and never in isolation. PMID- 25110991 TI - Smarter hospital communication: secure smartphone text messaging improves provider satisfaction and perception of efficacy, workflow. AB - BACKGROUND: Though current hospital paging systems are neither efficient (callbacks disrupt workflow), nor secure (pagers are not Health Insurance Portability and Accountability Act [HIPAA]-compliant), they are routinely used to communicate patient information. Smartphone-based text messaging is a potentially more convenient and efficient mobile alternative; however, commercial cellular networks are also not secure. OBJECTIVE: To determine if augmenting one-way pagers with Medigram, a secure, HIPAA-compliant group messaging (HCGM) application for smartphones, could improve hospital team communication. DESIGN: Eight-week prospective, cluster-randomized, controlled trial SETTING: Stanford Hospital INTERVENTION: Three inpatient medicine teams used the HCGM application in addition to paging, while two inpatient medicine teams used paging only for intra-team communication. MEASUREMENTS: Baseline and post-study surveys were collected from 22 control and 41 HCGM team members. RESULTS: When compared with paging, HCGM was rated significantly (P < 0.05) more effective in: (1) allowing users to communicate thoughts clearly (P = 0.010) and efficiently (P = 0.009) and (2) integrating into workflow during rounds (P = 0.018) and patient discharge (P = 0.012). Overall satisfaction with HCGM was significantly higher (P = 0.003). 85% of HCGM team respondents said they would recommend using an HCGM system on the wards. CONCLUSIONS: Smartphone-based, HIPAA-compliant group messaging applications improve provider perception of in-hospital communication, while providing the information security that paging and commercial cellular networks do not. PMID- 25110992 TI - Identification of cleavage sites leading to the shed form of the anti-aging protein klotho. AB - Membrane protein shedding is a critical step in many normal and pathological processes. The anti-aging protein klotho (KL), mainly expressed in kidney and brain, is secreted into the serum and CSF, respectively. KL is proteolytically released, or shed, from the cell surface by ADAM10 and ADAM17, which are the alpha-secretases that also cleave the amyloid precursor protein and other proteins. The transmembrane KL is a coreceptor with the FGF receptor for FGF23, whereas the shed form acts as a circulating hormone. However, the precise cleavage sites in KL are unknown. KL contains two major cleavage sites: one close to the juxtamembrane region and another between the KL1 and KL2 domains. We identified the cleavage site involved in KL release by mutating potential sheddase(s) recognition sequences and examining the production of the KL extracellular fragments in transfected COS-7 cells. Deletion of amino acids T958 and L959 results in a 50-60% reduction in KL shedding, and an additional P954E mutation results in further reduction of KL shedding by 70-80%. Deletion of amino acids 954-962 resulted in a 94% reduction in KL shedding. This mutant also had moderately decreased cell surface expression, yet had overall similar subcellular localization as that of WT KL, as demonstrated by immunofluorescence. Cleavage resistant mutants could function as a FGFR coreceptor for FGF23, but they lost activity as a soluble form of KL in proliferation and transcriptional reporter assays. Cleavage between the KL1 and KL2 domains is dependent on juxtamembrane cleavage. Our results shed light onto mechanisms underlying KL release from the cell membrane and provide a target for potential pharmacologic interventions aimed at regulating KL secretion. PMID- 25110994 TI - Feasibility of reirradiation in the treatment of locally recurrent rectal cancer (Br J Surg 2014; 101: 1280-1289). PMID- 25110993 TI - Thirty-day hospital readmissions in systemic lupus erythematosus: predictors and hospital- and state-level variation. AB - OBJECTIVE: Systemic lupus erythematosus (SLE) has one of the highest hospital readmission rates among chronic conditions. This study was undertaken to identify patient-level, hospital-level, and geographic predictors of 30-day hospital readmissions associated with SLE. METHODS: Using hospital discharge databases from 5 geographically dispersed states, we studied all-cause readmission of SLE patients between 2008 and 2009. We evaluated each hospitalization as a possible index event leading up to a readmission, our primary outcome. We accounted for clustering of hospitalizations within patients and within hospitals and adjusted for hospital case mix. Using multilevel mixed-effects logistic regression, we examined factors associated with 30-day readmission and calculated risk standardized hospital-level and state-level readmission rates. RESULTS: We examined 55,936 hospitalizations among 31,903 patients with SLE. Of these hospitalizations, 9,244 (16.5%) resulted in readmission within 30 days. In adjusted analyses, age was inversely related to risk of readmission. African American and Hispanic patients were more likely to be readmitted than white patients, as were those with Medicare or Medicaid insurance (versus private insurance). Several clinical characteristics of lupus, including nephritis, serositis, and thrombocytopenia, were associated with readmission. Readmission rates varied significantly between hospitals after accounting for patient-level clustering and hospital case mix. We also found geographic variation, with risk adjusted readmission rates lower in New York and higher in Florida as compared to California. CONCLUSION: We found that ~1 in 6 hospitalized patients with SLE were readmitted within 30 days of discharge, with higher rates among historically underserved populations. Significant geographic and hospital-level variation in risk-adjusted readmission rates suggests potential for quality improvement. PMID- 25110998 TI - One-pot transformation of cellobiose to formic acid and levulinic acid over ionic liquid-based polyoxometalate hybrids. AB - Currently, levulinic acid (LA) and formic acid (FA) are considered as important carbohydrates for the production of value-added chemicals. Their direct production from biomass will open up a new opportunity for the transformation of biomass resource to valuable chemicals. In this study, one-pot transformation of cellobiose into LA and FA was demonstrated, using a series of multiple-functional ionic liquid-based polyoxometalate (IL-POM) hybrids as catalytic materials. These IL-POMs not only markedly promoted the production of valuable chemicals including LA, FA and monosaccharides with high selectivities, but also provided great convenience of the recovery and the reuse of the catalytic materials in an environmentally friendly manner. Cellobiose conversion of 100%, LA selectivity of 46.3%, and FA selectivity of 26.1% were obtained at 423 K and 3 MPa for 3 h in presence of oxygen. A detailed catalytic mechanism for the one-pot transformation of cellobiose was also presented. PMID- 25110999 TI - Late mortality among 5-year survivors of early onset cancer: a population-based register study. AB - To date, only few studies have been published documenting late mortality among early onset cancer survivors, especially regarding young adulthood (YA) malignancies. Our nation-wide population-based registry study provides information concerning cause-specific long-term mortality among 16,769 5-year survivors of early onset cancer (aged 0-34 years at diagnosis), with follow-up for death extending from 1971 through 2012. A sibling cohort and population data were used as reference. The overall standardized mortality ratio (SMR) of cancer patients was 4.6-fold, (95% CI 4.4-4.8). Highest SMRs were found for malignancies (12.8, 95% CI 12.3-13.3), infectious (4.8, 95%CI 2.9-6.7) and cardiovascular diseases (1.9, 95% CI 1.7-2.1). Malignancies and cardiovascular diseases accounted for the largest number of deaths. Childhood and YA cancer survivors with the same primary cancer site had a similarly elevated overall SMR with the exception of markedly higher SMRs after childhood Hodgkin lymphoma. The highest cumulative non-malignancy-related mortality was due to cardiovascular disease with a steady rise throughout the follow-up, but strongly dependent on the primary cancer site and age at diagnosis. In childhood cancer survivors, the cumulative cardiovascular mortality did not reduce over time. However, overall and malignancy-related mortality showed a declining tendency towards the most recent periods after both, childhood and YA cancer. Our findings on non malignancy-related mortality stress the need to set up long-term individual follow-up with a focus on cardiovascular late effects for early onset cancer survivors, especially for YA cancer survivors still lacking those. PMID- 25111000 TI - New insights on the antidepressant discontinuation syndrome. AB - OBJECTIVE: Antidepressants are at best 50-55% effective. Non-compliance and the antidepressant discontinuation syndrome (ADS) are causally related yet poorly appreciated. While ADS is associated with most antidepressants, agomelatine seems to be devoid of such risk. We review the neurobiology and clinical consequences of antidepressant non-compliance and the ADS. Agomelatine is presented as a counterpoint to learn more on how ADS risk is determined by pharmacokinetics and pharmacology. DESIGN: The relevant literature is reviewed through a MEDLINE search via PubMed, focusing on agomelatine and clinical and preclinical research on ADS. RESULTS: Altered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic-nitrergic systems. CONCLUSIONS: This review raises awareness of the long-term negative aspects of non-compliance and inappropriate antidepressant discontinuation, and suggests possible approaches to "design-out" a risk for ADS. It reveals intuitive and rational ideas for antidepressant drug design, and provides new thoughts on antidepressant pharmacology, ADS risk and how these affect long-term outcome. PMID- 25111001 TI - Anticoagulant therapy in head injury-associated cerebral sinovenous thrombosis in children. AB - BACKGROUND: Head injury is a risk factor for cerebral sinovenous thrombosis (CSVT) in children. Literature concerning head injury-associated CSVT (HIA-CSVT) is scarce. Data supporting safety and efficacy of anticoagulant therapy (ACT) in childhood CSVT is emerging. However, intracranial hemorrhage (ICH) occurs frequently in children with HIA-CSVT at diagnosis making initiation of ACT controversial due to the fear of worsening of ICH. PROCEDURE: We conducted a retrospective descriptive review of a consecutive cohort of children with HIA CSVT from 1998 to 2012. RESULTS: Twenty patients (14 males, mean age 7 years) with HIA-CSVT were identified. Most (19/20 [95%]) had significant ICH at diagnosis. None received ACT at diagnosis. Fourteen (70%) were later (median 7 days post-trauma, range 2-48 days) treated with ACT due to CSVT persistence (nine) and propagation (five), despite ICH in 13. None of the treated patients, including the 13 with pre-existing ICH, had significant worsening of hemorrhage. Three (21%) treated patients had minor asymptomatic extension of their hemorrhage and further ACT was withheld. No patient died while on ACT. No patient experienced CSVT propagation on ACT. Clinical outcomes were normal (no neurologic deficits) in 5/20(25%), mild neurological deficits in 10/20(50%), and moderate severe neurological deficits in 5/20(25%). Small sample size did not permit assessment of the effect of ACT on outcome. CONCLUSIONS: Anticoagulant therapy is safe in selected children with HIA-CSVT. ICH is not an absolute contraindication to ACT in children with HIA-CSVT. PMID- 25111002 TI - Distribution and presumed proliferation of macrophages in inflammatory diseases of the ocular adnexae. AB - PURPOSE: The aim of this article is to investigate whether macrophages show a proliferative activity (as indicated by Ki67 expression) and their distribution at the site of inflammation. MATERIALS AND METHODS: Six different macrophage containing lesions from six different patients (four females, two males; age range: 16-58 years) were stained for macrophage markers (CD68, CD163) and Ki67 by immunohistochemistry. Immunofluorescence techniques were used to investigate dual labeling of the specimens for CD68, CD163 and Ki67, respectively. RESULTS: With immunofluorescence staining, scattered cells in all specimens were dual-labeled for CD68-Ki67 and CD163-Ki67. All lesions were composed of mixed infiltrates of M1 (CD68+CD163-) and M2 (CD68+CD163+) macrophages. The center of epithelioid-cell granulomas and foreign body giant cells was exclusively composed of M1 macrophages. CONCLUSIONS: This study shows that CD68+ and CD163+ cells express Ki67, a marker for proliferative activity at the site of inflammation. Until recently, macrophages were regarded as end-differentiated cells without mitotic activity. Since self-renewal of M1 and M2 macrophages has been described in the literature, staining of macrophages with Ki67 may indicate proliferative activity or at least an activation state. The distribution of macrophages in classic granulomatous lesions with only M1 macrophages in the avascular center represents an immune response to foreign body material, whereas the proangiogenic M2 macrophages are located mostly in the surrounding inflammatory tissue and seem to be mandatory for the vascularization of the inflammatory tissue. PMID- 25111003 TI - Random whole metagenomic sequencing for forensic discrimination of soils. AB - Here we assess the ability of random whole metagenomic sequencing approaches to discriminate between similar soils from two geographically distinct urban sites for application in forensic science. Repeat samples from two parklands in residential areas separated by approximately 3 km were collected and the DNA was extracted. Shotgun, whole genome amplification (WGA) and single arbitrarily primed DNA amplification (AP-PCR) based sequencing techniques were then used to generate soil metagenomic profiles. Full and subsampled metagenomic datasets were then annotated against M5NR/M5RNA (taxonomic classification) and SEED Subsystems (metabolic classification) databases. Further comparative analyses were performed using a number of statistical tools including: hierarchical agglomerative clustering (CLUSTER); similarity profile analysis (SIMPROF); non-metric multidimensional scaling (NMDS); and canonical analysis of principal coordinates (CAP) at all major levels of taxonomic and metabolic classification. Our data showed that shotgun and WGA-based approaches generated highly similar metagenomic profiles for the soil samples such that the soil samples could not be distinguished accurately. An AP-PCR based approach was shown to be successful at obtaining reproducible site-specific metagenomic DNA profiles, which in turn were employed for successful discrimination of visually similar soil samples collected from two different locations. PMID- 25111004 TI - Immunoglobulin light chain amyloidosis is diagnosed late in patients with preexisting plasma cell dyscrasias. AB - AL amyloidosis (AL) is rare and frequently remains undiagnosed until organ function is compromised, even among patients with known pre-existing untreated plasma cell dyscrasias (PCD). We identified 168 patients with AL amyloidosis who had a prior untreated PCD. The earliest symptom or sign (s/s) was defined as the first symptom reported by the patient that could be attributed to organ dysfunction caused by AL. The interval from the time of development of s/s to the establishment of diagnosis of AL (Interval-SA) was calculated. PCD diagnosis preceded recorded onset of s/s in 75% (114/152) of patients, with a median interval-SA for this group of 10 months. PCD was diagnosed after s/s in 25% (38/152) of patients, with a median interval-SA of 20 months. Overall survival (OS) from diagnosis of AL was not different between the two groups. AL amyloidosis patients with an identified pre-existing PCD had less advanced cardiac disease at AL diagnosis when compared to a control group of AL patients without pre-identified PCD. Long-term OS was not significantly superior among patients with a pre-identified PCD. In patients with "asymptomatic" PCD, symptoms and signs of AL amyloidosis should be solicited, since timely diagnosis is important in AL amyloidosis. PMID- 25111006 TI - Hyperpolarized [1,(13)C]pyruvate in lysed human erythrocytes: effects of co substrate supply on reaction time courses. AB - Hyperpolarized [1,(13)C]pyruvate was injected rapidly into haemolysates in which hydrolysis of nicotinamide adenine dinucleotide (phosphate) (NAD(P))/NAD(P)H had been inhibited with nicotinamide. Haemolysates provide a stable glycolytic system in which membrane permeability is not a flux-controlling step, and they enable the concentration of NADH to be adjusted experimentally while keeping the rest of the sample with the same composition as that of the cytoplasm of the cell (albeit diluted twofold at the time of injection of the [1,(13)C]pyruvate). We showed that the maximum amplitude of the (13)C NMR signal from the [1,(13)C]L-lactate, produced from [1,(13)C]pyruvate, and the time at which it occurred was dependent on NADH concentration, as predicted by enzyme-kinetic analysis. The main feature of such curves was dictated by the immediacy of the supply of the co-substrate of lactate dehydrogenase (LDH, EC 1.1.1.27), and we posit that this also pertains in vivo in various tissues including neoplasms. By constructing an appropriate mathematical model and by using a Markov-chain Monte Carlo approach, we fitted experimental data to estimate LDH and NADH concentrations. Experiments carried out with only endogenous NADH present enabled the estimation of its effective concentration in human RBCs; the ability to make this estimate is a special feature of the rapid-dissolution dynamic nuclear polarization method. We found an endogenous NADH concentration in human RBCs two to four times higher than previously reported. PMID- 25111005 TI - RAD9 enhances radioresistance of human prostate cancer cells through regulation of ITGB1 protein levels. AB - BACKGROUND: Mouse embryonic stem cells null for Rad9 are sensitive to deleterious effects of ionizing radiation exposure. Likewise, integrin beta1 is a known radioprotective factor. Previously, we showed that RAD9 downregulation in human prostate cancer cells reduces integrin beta1 protein levels and ectopic expression of Mrad9 restores inherent high levels. METHODS: We used RNA interference to knockdown Rad9 expression in PC3 and DU145 prostate cancer cells. These cells were then exposed to ionizing radiation, and integrin beta1 protein levels were measured by immunoblotting. Survival of irradiated cells was measured by clonogenicity, cell cycle analysis, PARP-1 cleavage, and trypan blue exclusion. RESULTS: The function of RAD9 in controlling integrin beta1 expression is unique and not shared by the other members of the 9-1-1 complex, HUS1 and RAD1. RAD9 or integrin beta1 silencing sensitizes DU145 and PC3 cells to ionizing radiation. Irradiation of DU145 cells with low levels of RAD9 induces cleavage of PARP-1 protein. High levels of ionizing radiation have no effect on integrin beta1 protein levels. However, when RAD9 downregulation is combined with 10 Gy of ionizing radiation in DU145 or PC3 cells, there is an additional 50% downregulation of integrin beta1 compared with levels in unirradiated RAD9 knockdown cells. Finally, PC3 cells growing on fibronectin display increased radioresistance. However, PC3 cells with RAD9 knockdown are no longer protected by fibronectin after treatment with ionizing radiation. CONCLUSIONS: Downregulation of RAD9 when combined with ionizing radiation results in reduction of ITGB1 protein levels in prostate cancer cells, and increased lethality. PMID- 25111007 TI - Strongly correlated alignment of fluorinated 5,11 bis(triethylgermylethynyl)anthradithiophene crystallites in solution-processed field-effect transistors. AB - The crystallinity of an organic semiconductor film determines the efficiency of charge transport in electronic devices. This report presents a micro-to-nanoscale investigation on the crystal growth of fluorinated 5,11 bis(triethylgermylethynyl)anthradithiophene (diF-TEG-ADT) and its implication for the electrical behavior of organic field-effect transistors (OFETs). diF-TEG-ADT exhibits remarkable self-assembly through spin-cast preparation, with highly aligned edge-on stacking creating a fast hole-conducting channel for OFETs. PMID- 25111008 TI - Microwave-assisted formation of organic monolayers from 1-alkenes on silicon carbide. AB - The rate of formation of covalently linked organic monolayers on HF-etched silicon carbide (SiC) is greatly increased by microwave irradiation. Upon microwave treatment for 60 min at 100 degrees C (60 W), 1-alkenes yield densely packed, covalently attached monolayers on flat SiC surfaces, a process that typically takes 16 h at 130 degrees C under thermal conditions. This approach was extended to SiC microparticles. The monolayers were characterized by X-ray photoelectron spectroscopy and static water contact angle measurements. The microwave-assisted reaction is compatible with terminal functionalities such as alkenes that enable subsequent versatile "click" chemistry reactions, further broadening the range and applicability of chemically modified SiC surfaces. PMID- 25111009 TI - Structure and conformation of the medium-sized chlorophosphazene rings. AB - Medium-sized cyclic oligomeric phosphazenes [PCl2N]m (where m = 5-9) that were prepared from the reaction of PCl5 and NH4Cl in refluxing chlorobenzene have been isolated by a combination of sublimation/extraction and column chromatography from the predominant products [PCl2N]3 and [PCl2N]4. The medium-sized rings [PCl2N]m have been characterized by electrospray ionization-mass spectroscopy (ESI-MS), their (31)P chemical shifts have been reassigned, and their T1 relaxation times have been obtained. Crystallographic data has been recollected for [PCl2N]5, and the crystal structures of [PCl2N]6, and [PCl2N]8 are reported. Halogen-bonding interactions were observed in all the crystal structures of cyclic [PCl2N]m (m = 3-5, 6, 8). The crystal structures of [P(OPh)2N]7 and [P(OPh)2N]8, which are derivatives of the respective [PCl2N]m, are also reported. Comparisons of the intermolecular forces and torsion angles of [PCl2N]8 and [P(OPh)2N]8 with those of three other octameric rings are described. The comparisons show that chlorophosphazenes should not be considered prototypical, in terms of solid-state structure, because of the strong influence of halogen bonding. PMID- 25111010 TI - Triterpenoids of Ganoderma theaecolum and their hepatoprotective activities. AB - Five new lanostane triterpenoids, ganoderic acid XL1 (1), ganoderic acid XL2 (2), 20-hydroxy-ganoderic acid AM1 (3), ganoderenic acid AM1 (4) and ganoderesin C (5), together with five known triterpenoids (6-10) were isolated from the fruiting bodies of Ganoderma theaecolum. Chemical structures were elucidated on the basis of spectroscopic evidence, including 1D, 2D NMR, mass spectrometric data and circular dichroism spectra. Compounds 1, 4, 5, 8, 9 and 10 (10 MUM) exhibited hepatoprotective activities against DL-galactosamine-induced cell damage in HL-7702 cells. PMID- 25111011 TI - Chemical investigation of the medicinal and ornamental plant Angelonia angustifolia Benth. reveals therapeutic quantities of lupeol. AB - Angelonia angustifolia Benth. is a small herbaceous plant with documented use as an anti-inflammatory remedy by indigenous cultures in Latin America. It has subsequently been developed as an ornamental annual widely available in nurseries in the United States. Chemical investigation led to the discovery that lupeol is the major organic soluble constituent in the roots, and is present in large quantities in the aerial structures of the plant. Lupeol was identified by 1D and 2D NMR spectroscopic techniques and quantified by HPLC-MS. The concentration of lupeol (9.14 mg/g in roots) in A. angustifolia is approximately 3 times higher than any previously reported sources. Therefore, the amount of lupeol in the roots of a single individual of A. angustifolia greatly exceeds the previously determined topical threshold for significant reduction of inflammation. The presence of topically therapeutic levels of lupeol in A. angustifolia provides chemical rationale for its indigenous use. In addition, the established cultivation of A. angustifolia could allow this plant to be used as a source of the important bioactive molecule lupeol, or to be developed as a nutraceutical without damaging wild populations. PMID- 25111013 TI - Health-related quality of life of adolescent and young adult survivors of childhood brain tumors. AB - OBJECTIVE: Our aim was to expand research on predictors of health-related quality of life (HRQOL) for adolescent and young adult survivors of childhood brain tumors who are not living independently by evaluating the mediating role of family functioning in the association of disease severity/treatment late effects with survivor self-report and caregiver-proxy report of physical and emotional HRQOL. METHODS: Mothers (N = 186) and their survivors living at home (N = 126) completed self-report and caregiver-proxy report of physical and emotional HRQOL. Mothers completed family functioning measures of general family functioning, caregiving demands, and caregiver distress. Medical file review and caregiver report were used to evaluate disease severity/treatment late effects. RESULTS: Using structural equation models, family functioning was adjusted for sociodemographic factors. Disease severity/treatment late effects had significant direct effects on self-report and caregiver-proxy report of physical and emotional HRQOL. Family functioning had a significant direct effect on caregiver proxy report of physical and emotional HRQOL, but these findings were not confirmed for self-report HRQOL. Model-fit indices suggested good fit of the models, but the mediation effect of family functioning was not supported. CONCLUSIONS: Disease severity/treatment late effects explained self-report and caregiver-proxy report of physical and emotional HRQOL for these adolescent and young adult survivors of childhood brain tumors. Family functioning was implicated as an important factor for caregiver-proxy report only. To enhance physical and emotional HRQOL, findings underscore the importance of coordinated, multidisciplinary follow-up care for the survivors who are not living independently and their families to address treatment late effects and support family management. PMID- 25111014 TI - Chimeric recombinant antibody fragments in cardiac troponin I immunoassay. AB - OBJECTIVES: To introduce a novel nanoparticle-based immunoassay for cardiac troponin I (cTnI) utilizing chimeric antibody fragments and to demonstrate that removal of antibody Fc-part and antibody chimerization decrease matrix related interferences. DESIGN AND METHODS: A sandwich-type immunoassay for cTnI based on recombinant chimeric (mouse variable/human constant) antigen binding (cFab) antibodies and intrinsically fluorescent nanoparticles was developed. To test whether using chimeric antibody fragments helps to avoid matrix related interferences, samples (n=39) with known amounts of triglycerides, bilirubin, rheumatoid factor (RF) or human anti-mouse antibodies (HAMAs) were measured with the novel assay, along with a previously published nanoparticle-based research assay with the same antibody epitopes. RESULTS: The limit of detection (LoD) was 3.30ng/L. Within-laboratory precision for 29ng/L and 2819ng/L cTnI were 13.7% and 15.9%, respectively. Regression analysis with Siemens ADVIA Centaur(r) yielded a slope (95% confidence intervals) of 0.18 (0.17-1.19) and a y-intercept of 1.94 ( 1.28-3.91) ng/L. When compared to a previously published nanoparticle-based assay, the novel assay showed substantially reduced interference in the tested interference prone samples, 15.4 vs. 51.3%. A rheumatoid factor containing sample was decreased from 241ng/L to =17), but risks were also increased for some T-cell lymphomas (SIRs = 3.6-14.2), marginal zone lymphoma (SIR = 2.4), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (SIR = 3.6), and acute lymphoblastic leukemia/lymphoma (SIR = 2.4). CONCLUSION: HIV-infected people in the HAART era continue to have elevated risk of AIDS-defining NHL subtypes, highlighting the contribution of moderate and severe immunosuppression to their cause. Whereas non-AIDS-defining subtypes are much less common, immunosuppression or other dysregulated immune states likely play a role in the cause of some T-cell lymphomas, marginal zone lymphoma, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, and acute lymphoblastic leukemia/lymphoma. PMID- 25111082 TI - Efficacy of prolonged tenofovir therapy on hepatitis delta in HIV-infected patients. AB - BACKGROUND: Hepatitis delta virus (HDV) produces the most severe form of chronic viral hepatitis. We explored whether prolonged tenofovir exposure might be beneficial on hepatitis delta in HIV-infected patients. METHODS: All HIV-infected patients with hepatitis delta followed at our institution since year 2000 were retrospectively examined. Serum HBV-DNA and HDV-RNA were quantified using commercial assays. Liver fibrosis was measured using elastometry. RESULTS: A total of 19 HIV/delta patients were identified. All were viremic for HDV and 11 for HBV. After a median tenofovir exposure of 58 months, all had undetectable HBV DNA and 10 (53%) had undetectable HDV-RNA. The median drop in HDV-RNA in the remaining nine HDV viremic patients at the end of follow-up was 2.4 log copies/ml. A reduction above 30% in liver stiffness occurred in six out 10 (60%) patients who achieved undetectable HDV-RNA, whereas hepatic stiffness did not change in the remaining HDV viremic patients (P = 0.03). Serum HBsAg concentrations did not decline significantly, although HBsAg seroclearance occurred in three patients, all of whom became negative for HDV-RNA. CONCLUSION: Long-term exposure to tenofovir significantly reduced serum HDV-RNA apart from completely suppressing HBV-DNA in HIV-infected patients with hepatitis delta. This virological benefit is accompanied by significant improvements in liver fibrosis. PMID- 25111083 TI - Influence of hepatitis C virus coinfection on CD4+ T cells of HIV-infected patients receiving HAART. AB - OBJECTIVE: The effects of hepatitis C virus (HCV) coinfection on immune homeostasis and immune restoration in treated HIV infection are not well understood. METHODS: We studied 79 HIV-infected patients who had been receiving HAART for more than 2 years and who had HIV viral load below 50 copies/ml. Four patient groups were studied: HIV/HCV, CD4+ cells above 350/MUl; HIV/HCV, CD4 cells below 350/MUl; HIV/HCV, CD4 cells above 350/MUl; HIV/HCV, CD4+ cells below 350/MUl. Controls comprised 20 healthy volunteers. Naive, central memory, effector memory, and terminal effector CD4+ T cells were enumerated. Naive CD4CD31 T cells were counted as recent thymic emigrants (RTEs). Activation state and ex-vivo apoptosis of CD4+ T cells, levels of liver enzymes, and aspartate aminotransferase-to-platelet ratio index were evaluated. RESULTS: CD4+ T-cell counts and the numbers of all circulating CD4 T-cell maturation subsets were diminished in HIV infection; CD4+ T-cell activation and apoptosis were increased in HIV infection, but none of these indices was affected by HCV coinfection. RTE numbers were diminished in HIV infection, were inversely related to age, and were increased in women and lower in HIV/HCV patients than in singly HIV-infected patients. In coinfected patients, RTE numbers were inversely related to levels of liver enzymes, but not to HCV viral load. CONCLUSION: Whereas we could find no relationship between HCV infection and most indices of CD4+ T-cell homeostasis or activation, CD4+ RTEs are diminished in the circulation of HCV coinfected persons and appear to be related to indices of ongoing hepatic damage or inflammation. PMID- 25111085 TI - Sex-specific differences in offspring personalities across the laying order in magpies Pica pica. AB - Maternal effects provide an important mechanism for mothers to create variation in offspring personality, and to potentially influence offspring life history strategies e.g. creating more/less dispersive phenotypes. However, within-clutch maternal effects often vary and hence there is potential for within-clutch variation in personality. We studied the effects of hatching order on explorative and neophobic behaviour of the magpies Pica pica in relation to sex using novel environment and novel object experiments. Hatching order did affect explorative behaviour in magpie, but did so in opposite directions for either sex. First hatched females were more explorative and had a tendency to be less neophobic, whereas in males, the reverse was true. Our results suggest that hormonal as well as post-natal environmental mechanisms could be underpinning this pattern. Future research is needed to fully understand the importance of both in creating different offspring personalities. This article is part of a Special Issue entitled: insert SI title. PMID- 25111086 TI - Validated HPLC method for simultaneous estimation of khellol glucoside, khellin and visnagin in Ammi visnaga L. fruits and pharmaceutical preparations. AB - Tea bags including fruits of Ammi visnaga L. are used in Egypt as remedy for the treatment of kidney stones. Our study focuses on developing simple and rapid method utilising HPLC for quantitative estimation of khellol glucoside (KG), khellin (KH) and visnagin (VS) simultaneously. Their concentrations were determined in A. visnaga L. fruits at different developmental stages and in pharmaceutical formulations together with following up them during shelf life. Separation was accomplished using HPLC. Perfect resolution between KG, KH and VS was possible through using a mobile phase consisting of water:methanol:tetrahydrofuran (50:45:5, v/v/v). Peaks were detected at 245 nm. The suggested method for the determination of KG, KH and VS was successful in determining the analytes of interest without any interference of other compounds and matrix. All validation parameters were satisfactory and the procedure was relatively easy and fast as extracts are evaluated without previous steps of purification. PMID- 25111084 TI - The proteome of cholesteryl-ester-enriched versus triacylglycerol-enriched lipid droplets. AB - Within cells, lipids are stored in the form of lipid droplets (LDs), consisting of a neutral lipid core, surrounded by a phospholipid monolayer and an outer layer of protein. LDs typically accumulate either triacylglycerol (TAG) and diacylglycerol or cholesteryl ester (CE), depending on the type of tissue. Recently, there has been an increased interest in the proteins that surround LDs. LD proteins have been found to be quite diverse, from structural proteins to metabolic enzymes, proteins involved in vesicular transport, and proteins that may play a role in LD formation. Previous proteomics analyses have focused on TAG enriched LDs, whereas CE-enriched LDs have been largely ignored. Our study has compared the LD proteins from CE-enriched LDs to TAG-enriched LDs in steroidogenic cells. In primary rat granulosa cells loaded with either HDL to produce CE-enriched LDs or fatty acids to produce TAG-enriched LDs, 61 proteins were found to be elevated in CE-enriched LDs and 40 proteins elevated in TAG enriched LDs with 278 proteins in similar amounts. Protein expression was further validated by selected reaction monitoring (SRM) mass spectrometry (MS). SRM verified expression of 25 of 27 peptides that were previously detected by tandem mass tagging MS. Several proteins were confirmed to be elevated in CE-enriched LDs by SRM including the intermediate filament vimentin. This study is the first to compare the proteins found on CE-enriched LDs with TAG-enriched LDs and constitutes the first step in creating a better understanding of the proteins found on CE-enriched LDs in steroidogenic cells. PMID- 25111087 TI - Design of functional nanoparticles and assemblies for theranostic applications. AB - Nanostructured materials have found increasing applications in medical therapies and diagnostics (theranostics). The main challenge is the ability to impart the nanomaterials with structurally tailored functional properties which can effectively target biomolecules but also provide signatures for effective detection. The harnessing of functional nanoparticles and assemblies serves as a powerful strategy for the creation of the structurally tailored multifunctional properties. This article highlights some of the important design strategies in recent investigation of metals (especially gold and silver), and magnetically functionalized nanoparticles, and molecularly assembled or biomolecularly conjugated nanoparticles with tunable optical, spectroscopic, magnetic, and electrical properties for applications in several areas of potential theranostic interests. Examples include colorimetric detection of amino acids and small peptides, surface-enhanced Raman scattering detection of biomolecular recognition of proteins and DNAs, delivery in cell transfection and bacteria inactivation, and chemiresistive detection of breath biomarkers. A major emphasis is placed on understanding how the control of the nanostructures and the molecular and biomolecular interactions impact these biofunctional properties, which has important implications for bottom-up designs of theranostic materials. PMID- 25111088 TI - Effect of hydroxyapatite nanoparticles on osmotic responses of pig iliac endothelial cells. AB - In order to fully explore the potential applications of nanoparticles in biopreservation, it is necessary to study the effect of nanoparticles on cell membrane permeabilities. The aim of this study is therefore to comparatively evaluate the osmotic responses of pig iliac endothelial cells in the absence and presence of commercially available hydroxyapatite nanoparticles. The results indicate that, after the introduction of 0.0 1 wt% hydroxyapatite nanoparticles, the dependence of cell membrane hydraulic conductivity (Lp) on temperature still obeys the Arrhenius relationship, while the reference value of the hydraulic conductivity of the cell membrane at 273.15K (Lpg) and the activation energy for water transport across cell membrane (ELp) change from 0.77 * 10(-14)m/Pa/s and 15.65 kJ/mol to 0.65 * 10(-14)m/Pa/s and 26.14 kJ/mol. That is to say, the reference value of the hydraulic conductivity of the cell membrane has been slightly decreased while the activation energy for water transport across cell membrane has been greatly enhanced, and thus it implies that the hydraulic conductivity of cell membrane are more sensitive to temperature in the presence of nanoparticles. These findings are of potential significance to the optimization of nanoparticles-aided cryopreservation. PMID- 25111089 TI - Design and computational characterization of non-fullerene acceptors for use in solution-processable solar cells. AB - In an effort to seek high-performance small molecule electron acceptor materials for use in heterojunction solar cells, computational chemistry was used to examine a variety of terminal acceptor-conjugated bridge-core acceptor-conjugated bridge-terminal acceptor small molecules. In particular, we have systematically predicted the geometric, electronic, and optical properties of 16 potential small molecule acceptors based upon a series of electron deficient pi-conjugated building blocks that have been incorporated into materials exhibiting good electron transport properties. Results show that the band gap, HOMO/LUMO energy levels, orbital spatial distribution, and intrinsic dipole moments can be systematically altered by varying the electron properties of the terminal or core acceptor units. In addition, the identity of the conjugated bridge can help fine tune the electronic properties of the molecule, where this study showed that the strongest electron affinity of the conjugated pi-bridge increased the stability in the HOMO and LUMO energies and increased the band gap of these small-molecule acceptors. As a result, this work points toward an isoindigo (C5) core combined with C2-thienopyrrole dione (A5) terminal units as the most promising small molecule acceptor material that can be fine-tuned with the choice of conjugated bridge and may be considered as reasonable candidates for synthesis and incorporation into organic solar cells. PMID- 25111090 TI - Comparing criterion- and trait-based personality disorder diagnoses in DSM-5. AB - In the recent Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the official personality disorder (PD) classification system remains unchanged. However, DSM-5 also includes an alternative hybrid categorical-dimensional PD system in Section III to spur additional research. One defining feature of the alternative system is the incorporation of a trait model with PD-specific trait configurations, but relatively little work has evaluated how these traits map onto official PD diagnoses or their implications for diagnosis rates. To that end, we compared official PD criteria to Section III PD traits in a sample of current or recent psychiatric patients. We (a) evaluated the extent to which PD traits predicted traditional PD criterion counts, and (b) computed trait-based diagnosis rates and compared them to those reported in several published outpatient and epidemiological samples. Overall, PD traits generally predicted PD criterion counts, but with less than ideal specificity. In addition, we identified differences in diagnosis rates across approaches. These results provide some support for the Section III approach, but they also identify important areas in need of refinement and future study before the field could reasonably switch to a hybrid PD classification approach like that in Section III. PMID- 25111091 TI - The early access to medicines scheme. PMID- 25111092 TI - Guidance on multi-morbidity: the challenge facing NICE. PMID- 25111094 TI - Vasculitis: an update. AB - The systemic vasculitides are uncommon but serious diseases. Early recognition can be difficult because they mimic many conditions. Aggressive immunosuppression is toxic but effective; a targeted approach with biological agents may improve the outcome. PMID- 25111095 TI - Biologics in systemic lupus erythematosus: current options and future perspectives. AB - Data from clinical trials highlighted the potential and pitfalls of the use of biologics to treat systemic lupus erythematosus. With improved understanding of immunopathogenesis and lessons learned from controlled trials, there is a growing optimism for personalized treatment from an increasing range of targeted therapies. PMID- 25111096 TI - Biologics in rheumatoid arthritis: where are we going? AB - Biological disease-modifying antirheumatic drugs have significantly improved outcomes for patients with rheumatoid arthritis, but cost limits their use. This article assesses data on patients who have achieved remission or low disease activity with these drugs and the possibility of dose reduction or discontinuation in these patients. PMID- 25111097 TI - Why can't my child see 3D television? AB - A child encountering difficulty in watching three-dimensional (3D) stereoscopic displays could have an underlying ocular disorder. It is therefore valuable to understand the differential diagnoses and so conduct an appropriate clinical assessment to address concerns about poor 3D vision. PMID- 25111098 TI - Effective medical leadership development for a complex NHS. AB - The NHS Leadership Academy in England is investing L46 million in a standardized model of development, with academic qualifications becoming essential in future NHS leadership roles. This represents a cul-de-sac for medical leaders because it is based on a series of misplaced assumptions about health-care leadership and its development. PMID- 25111099 TI - How competent do graduates feel to undertake the skills required by the General Medical Council? AB - The General Medical Council outlines the skills medical students are meant to learn as undergraduates. This article summarizes how competent some foundation year one doctors from one deanery felt to undertake these skills, what had prepared them and what they would like more training on. PMID- 25111100 TI - Isolated myeloid sarcoma of the buccal region. PMID- 25111101 TI - Diogenes syndrome causing life-threatening complications of Paget's disease. PMID- 25111102 TI - Recurrent sinusitis: think granulomatosis with polyangiitis. PMID- 25111103 TI - Digestive enzyme supplements: replacement therapy for individuals unwilling to take porcine products. PMID- 25111104 TI - The outbreak of the first world war and the medical profession. PMID- 25111106 TI - Should the national early warning score be adopted throughout the NHS? PMID- 25111107 TI - In situ electrodeposition of an asymmetric sol-gel membrane based on an octadecyltrimethoxysilane Langmuir film. AB - The unique properties of Langmuir film formation were utilized in assembling a thin skin of an asymmetric membrane. An octadecyltrimethoxysilane (ODTMS) Langmuir monolayer was formed at the air-water interface and served as the substrate for growing a bulky sol-gel polymer in situ. The latter was based on the electrochemical deposition of tetramethoxysilane dissolved in the water subphase by means of horizontal touch electrochemistry. The resultant asymmetric layer that consisted of a thin hydrophobic ODTMS Langmuir film connected to a bulk hydrophilic sol-gel network was studied in situ and ex situ by using various techniques, such as cyclic voltammetry, electrochemical impedance spectroscopy (EIS), scanning electron microscopy, transmission electron microscopy (TEM), and goniometry. We found that a porous hydrophilic film grew on top of a hydrophobic layer as was evident from TEM, contact angle, and EIS analyses. The film thickness and film permeability could be controlled by changing the deposition conditions such as the potential window applied and its duration. Hence, this method offers an alternative approach for assembling asymmetric films for various applications. PMID- 25111108 TI - The association between prenatal sleep quality and obstetric outcome. AB - BACKGROUND: Pregnancy-associated sleep disorder is a new category on the latest version of the International Classification of Sleep Disorders. It is a significant problem for pregnant women. PURPOSE: The present follow-up study assesses the association between sleep quality during the second and third trimesters of pregnancy and obstetric-neonatal outcomes. METHODS: A prospective follow-up study design was used. Follow-up examination of the obstetric birth records in the immediate postpartum period were carried out on 128 second trimester and 120 third-trimester women and their newborns in two hospitals in Taiwan. Poor sleep quality was identified using the Pittsburgh Sleep Quality Index. Data were collected from October 2007 to June 2008. RESULTS: The prevalence of poor sleepers (Pittsburgh Sleep Quality Index score > 5) was 58% for second-trimester participants and 66% for third-trimester participants; participants who were unemployed reported a significantly higher prevalence of poor sleep quality than those who were employed. Subsequent review of the participant's obstetric birth records revealed that third-trimester poor sleepers were more likely to have had a vacuum-assisted delivery. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study identified poor sleep quality during the third trimester as a novel risk factor for vacuum-assisted delivery. We suggest that prenatal healthcare providers focus greater attention to the sleep disturbance condition of pregnant women and provide proactive sleep counseling to facilitate pregnant women's adjustment to the new psychosocial and physiological demands of motherhood. PMID- 25111109 TI - The effect of yoga exercise on improving depression, anxiety, and fatigue in women with breast cancer: a randomized controlled trial. AB - BACKGROUND: Depression, anxiety, and fatigue are among the most significant problems that influence the quality of life of patients with breast cancer who receive adjuvant chemotherapy. Although evidence has shown yoga to decrease anxiety, depression, and fatigue in patients with cancer, few studies on the effects of yoga have targeted patients with breast cancer. Yoga interventions should be tested to promote the psychological and physical health of women with breast cancer. PURPOSE: This study examines the effectiveness of an 8-week yoga exercise program in promoting the psychological and physical health of women with breast cancer undergoing adjuvant chemotherapy in terms of depression, anxiety, and fatigue. METHODS: A sample of 60 women with nonmetastatic breast cancer was recruited. Participants were randomly assigned into either the experimental group (n = 30) or the control group (n = 30). A 60-minute, twice-per-week yoga exercise was implemented for 8 weeks as the intervention for the participants in the experimental group. The control group received standard care only. RESULTS: Analysis using the Johnson-Neyman procedure found that the yoga exercise reduced overall fatigue and the interference of fatigue in everyday life for the experimental group participants. Significant reductions were obtained after 4 weeks of intervention participation for those experimental group patients with relatively low starting baseline values (baseline item mean value < 3.31 and 3.22, respectively) and after 8 weeks for most patients (approximately 75%) with moderate starting baseline values (baseline item mean value < 7.30 and 5.34, respectively). The 8-week intervention did not significantly improve the levels of depression (F = 1.29, p > .05) or anxiety (F = 2.7, p > .05). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The 8-week yoga exercise program developed in this study effectively reduced fatigue in patients with breast cancer but did not reduce depression or anxiety. Oncology nurses should strengthen their clinical health education and apply yoga to reduce the fatigue experienced by patients with breast cancer who undergo adjuvant chemotherapy. PMID- 25111110 TI - Factors affecting perceptions of family function in caregivers of children with attention deficit hyperactivity disorders. AB - BACKGROUND: Attention deficit and hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood. ADHD has been shown to persist into adulthood in 30%-70% of cases. The long-term and escalating nature of ADHD creates an increasing burden on families because of the influence of hyperactivity and impulsivity on academic achievement and social interaction. There is a lack of information on factors influencing function in the families of children with ADHD. PURPOSE: The purpose of this study was to test theoretically derived relationships among family demographic characteristics; family factors such as support, hardiness, and caregiver health; and family-functioning outcomes. METHODS: This study used a cross-sectional study and structural equation modeling approach. A self-report questionnaire collected information from 122 caregivers on demographics, income, employment, and marital status data as well as on personal health, family support, family hardiness, and family function statuses as determined, respectively, using the Duke Health Profile, Family APGAR score, Family Hardiness Index, and Family Assessment Device. RESULTS: Structural equation modeling provided a reasonable fit to the data using AMOS (chi = .249, df = 1, p = .613, minimum discrepancy C = .249), goodness-of fit index (.999), adjusted goodness of fit index (.990), normed fit index (.999), comparative fit index (1.0), and root mean square error of approximation (.000). Results indicated a 55.6% probability of becoming the construct model, with family hardiness and family support directly affecting family function and caregiver health. Family support functioned as a mediator in the relationship between family hardiness and family function. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings of this study help nurses improve professional assessments and interventions for families of children with ADHD by highlighting the importance of increased family support, promoting family hardiness, and promoting caregivers' health to improved family function. PMID- 25111111 TI - Exploring the relationship between personality features and teaching self efficacy in clinical nursing preceptors. AB - BACKGROUND: The clinical nursing preceptor system, first introduced in the 1960s, is a one-on-one education and practice model. Preceptorship programs assign experienced registered nurses (preceptors) as mentors or role models for new clinical nurses (preceptees). PURPOSE: The objective of this study was to delineate the relationship between personality features and teaching self efficacy in clinical nursing preceptors. METHODS: In June 2009, clinical nursing preceptors at a county hospital in Taiwan were asked to complete three questionnaires, including (a) background demographics, (b) Eysenck Personality Questionnaire, and (c) the teaching self-efficacy evaluation. A generalized linear model was applied to determine the associations between the six dimensions of teaching self-efficacy (maturity, teaching self-efficacy beliefs, professional skill, teaching strategy effectiveness, quality of interpersonal relationships, and objective teaching evaluation) and four dimensions related to personality features (extraversion, neuroticism, psychoticism, and the lie scale), adjusted for baseline characteristics. RESULTS: One hundred sixteen nurse preceptors (mean age = 31.2 years, range = 25-54 years) participated in this survey. Analysis showed that extraversion was related to higher scores for maturity, teaching self efficacy beliefs, professional skill, teaching strategy effectiveness, and objective teaching evaluation. A higher neuroticism score was negatively associated with maturity. The psychoticism score had no significant associations. A higher score on the lie scale was related to lower professional skill and less teaching strategy effectiveness. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Personality features relate significantly to teaching self-efficacy in nursing preceptors. This study identified personality features that may influence the success of nurses in becoming competent clinical preceptors. PMID- 25111112 TI - A rehabilitation program for Alzheimer's disease. AB - BACKGROUND: We present the design and implementation of a rehabilitation program (RP) adapted for people diagnosed with various phases of Alzheimer's disease (AD). The RP is a cognitive stimulation program that integrates the recommendations of the American College of Sports Medicine for aerobic, resistance, and balance exercises. PURPOSE: The aim of this study is to evaluate the effect of the RP on the physical and functional capacities, cognitive functions, and quality of life (QOL) of patients with AD. METHODS: We enrolled 64 participants with AD for an RP intervention lasting 12 months. The research used a quasiexperimental approach. Assessed variables included cognitive ability (Mini Mental State Examination), fitness (Chair Stand Test), level of independence (Barthel Index), and QOL (the 12-item Short Form Health Survey). Statistical analyses used the Student's t test, Mann-Whitney U test, and the chi-squared test. The statistical significance level was set at 5%. RESULTS: The results indicate the effectiveness of the RP in improving the physical fitness and the QOL of participants with mild- to moderate-phase AD. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The RP has a positive effect on patients with mild- to moderate-phase AD. However, we identified no effect for the RP on cognitive ability. These findings provide empirical evidence to support the use of RP as an effective complementary therapy. Improving the physical capacity and the QOL may have important long-term benefits for the older adults and their caregivers. The results of this study should be helpful to decision makers and geriatric health centers in planning and implementing RPs for elderly people with AD. PMID- 25111113 TI - Work-family conflict and job performance in nurses: the moderating effects of social support. AB - BACKGROUND: A large number of women are employed in the labor market. This phenomenon has widely supplanted the traditional family model of full-time working fathers and full-time housewives with the dual-income family model. Most nurses have both family and work responsibilities and hope to balance these two aspects of their lives. Work-family conflict (WFC) is thus a significant issue faced by professional nurses. PURPOSES: This study examines the relationship between WFC and job performance in the nursing context and explores the moderating effects of different sources of social support. METHODS: This study questionnaire used a self-reporting scale. To avoid common method variance, research data were collected at two time points. Five hundred twenty questionnaires were sent to nurses working at five hospitals in Taiwan, and 501 were returned, of which 495 were valid and used in analysis. Hierarchical regression analysis was used to test study hypotheses. RESULTS: Study findings were (a) degree of family-to-work conflict influenced job performance negatively, (b) level of WFC did not significantly affect job performance, (c) support from friends strengthened the negative effect of family-to-work conflict on job performance, and (d) support from coworkers weakened the relationship between WFC and job performance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: It is hoped that the findings of this study will be useful for nursing managers, organizations, and future research. Hospital organizations and nursing departments have a positive role to play in fostering an organizational culture that helps its staffs balance work and family responsibilities. A strategy of human resource management that is consistent with the demands of nurses may help reduce WFC. PMID- 25111114 TI - The link of sexual sensation seeking to acceptance of cybersex, multiple sexual partners, and one-night stands among Taiwanese college students. AB - BACKGROUND: Young people in Taiwan have become more liberal and active toward sex. Despite heavy investments of money, time, and effort, sexual education programs have generally lagged expectations. PURPOSE: Personality traits such as sexual sensation seeking are found to be significantly associated with risky sexual behaviors. This study, therefore, attempts to explore the link of sexual sensation seeking to acceptance by Taiwanese college students of cybersex, multiple sexual partners, and one-night stands. METHODS: A cross-sectional study was conducted using the multistage cluster sampling method. Five hundred sixteen students recruited from eight universities/colleges in Taiwan participated in this study, and 507 completed the self-report questionnaire. The valid response rate was 98.26%. RESULTS: The results reveal that high-sexual-sensation seekers were more likely than low-sexual-sensation seekers to accept cybersex, multiple sexual partners, and one-night stands. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study suggests that the designers of campus-based health prevention campaigns should target campaign messages on high-sexual-sensation seekers using novel, thrilling, and complex messages to achieve safe sex educational campaign goals. PMID- 25111115 TI - Do randomized controlled nursing trials have a pragmatic or explanatory attitude? Findings from the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool exercise. AB - BACKGROUND: Randomized controlled trials (RCTs) may be categorized as either effectiveness trials or efficacy trials, which may be categorized by the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool. However, no data regarding the application of the PRECIS tool in a cluster of RCTs belonging to a specific discipline such as nursing are available. PURPOSE: The principal aim of this study was to assess the prevailing nature (pragmatic vs. explanatory) of a cluster of clinical nursing RCTs. Evaluating the suitability of the PRECIS in the analysis of nursing RCTs was the secondary aim. METHODS: All nursing RCTs published in 2010 were identified through a systematic review and extracted in full-text form. An explanatory-pragmatic (E-P) group consisting of 11 researchers trained in the use of the PRECIS tool evaluated each RCT in terms of 10 domains, respectively scored on a scale ranging from 5 (pragmatic) to 1 (explanatory). The E-P group further scored the feasibility of the PRECIS tool using a numerical rating scale (0 = not at all, 10 = entirely feasible). RESULTS: Along the pragmatic-explanatory continuum, assuming 50 as the highest degree of pragmatism and 10 as the highest degree of explanatory, the evaluation of nursing RCTs returned an average of 31.1 (median = 31, SD = 7.18, range = 13-44). On the pragmatic-explanatory continuum, the evaluated nursing RCTs tended to be pragmatic, which seems to be consistent with the purposes of the nursing discipline. The feasibility of the PRECIS tool in the evaluation of nursing trials as perceived by the E-P Group was, on average, 7.09 (SD = 1.09, 95% CI [6.35, 7.82]). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Applying the PRECIS tool is perceived to be highly feasible in the critical appraisal of a cluster of RCTs in a specific discipline such as nursing. PMID- 25111116 TI - Trp28Arg/Ile35Thr LHB gene variants are associated with elevated testosterone levels in women with polycystic ovary syndrome. AB - INTRODUCTION: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder, of multifactorial etiology, which affects 6-10% of women of reproductive age. It is considered the leading cause of anovulatory infertility, menstrual disorders and hyperandrogenism in this population. The genetic basis of PCOS is still largely unknown despite significant family clustering; determining its mode of inheritance is particularly difficult given the heterogenic presentation of the disease. MATERIALS AND METHODS: 130 Brazilian women, aged 14-42 years, who met the 2003 Rotterdam criteria for PCOS diagnosis, were included, and 96 healthy women constituted the control group. Presence of hirsutism was classified using the modified Ferriman-Gallwey score (F-G score) as absent (<=7), mild (8-14), and severe (>=15). Blood levels of luteinizing hormone (LH), total testosterone (TT), dehydroepiandrosterone sulfate (DHEA-S) and androstenedione were determined. The coding region of the luteinizing hormone beta-subunit (LHB) gene was amplified and sequenced. Differences in allelic and genotypic frequency distribution of each polymorphism across controls and cases were estimated by the Mantel-Haenszel chi-square or Fisher's exact test (p<0.05), and the probability of an association between the detection of a polymorphism and presence of a diagnosis of PCOS, by logistic regression. RESULT(S): Sequencing detected 8 polymorphisms in the LHB gene coding region. Two polymorphisms in linkage disequilibrium were significantly more prevalent in the presence of hyperandrogenemia: rs1800447/rs34349826 (Trp28Arg/Ile35Thr) (p=0.02). CONCLUSION(S): In this series, a modulatory effect of LHB polymorphisms on hyperandrogenemia phenotype of PCOS was observed; however, this finding needs to be replicated in other populations. PMID- 25111117 TI - In-silico identification and characterization of organic and inorganic chemical stress responding genes in yeast (Saccharomyces cerevisiae). AB - To study the life processes of all eukaryotes, yeast (Saccharomyces cerevisiae) is a significant model organism. It is also one of the best models to study the responses of genes at transcriptional level. In a living organism, gene expression is changed by chemical stresses. The genes that give response to chemical stresses will provide good source for the strategies in engineering and formulating mechanisms which are chemical stress resistant in the eukaryotic organisms. The data available through microarray under the chemical stresses like lithium chloride, lactic acid, weak organic acids and tomatidine were studied by using computational tools. Out of 9335 yeast genes, 388 chemical stress responding genes were identified and characterized under different chemical stresses. Some of these are: Enolases 1 and 2, heat shock protein-82, Yeast Elongation Factor 3, Beta Glucanase Protein, Histone H2A1 and Histone H2A2 Proteins, Benign Prostatic Hyperplasia, ras GTPase activating protein, Establishes Silent Chromatin protein, Mei5 Protein, Nondisjunction Protein and Specific Mitogen Activated Protein Kinase. Characterization of these genes was also made on the basis of their molecular functions, biological processes and cellular components. PMID- 25111118 TI - Genotype-based databases for variants causing rare diseases. AB - Inherited diseases are the result of DNA sequence changes. In recessive diseases, the clinical phenotype results from the combined functional effects of variants in both copies of the gene. In some diseases there is often considerable variability of clinical presentation or disease severity, which may be predicted by the genotype. Additional effects may be triggered by environmental factors, as well as genetic modifiers which could be nucleotide polymorphisms in related genes, e.g. maternal ApoE or ABCA1 genotypes which may have an influence on the phenotype of SLOS individuals. Here we report the establishment of genotype variation databases for various rare diseases which provide individual clinical phenotypes associated with genotypes and include data about possible genetic modifiers. These databases aim to be an easy public access to information on rare and private variants with clinical data, which will facilitate the interpretation of genetic variants. The created databases include ACAD8 (isobutyryl-CoA dehydrogenase deficiency (IBD)), ACADSB (short-chain acyl-CoA dehydrogenase (SCAD) deficiency), AUH (3-methylglutaconic aciduria (3-MGCA)), DHCR7 (Smith Lemli-Opitz syndrome), HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency), HSD17B10 (17-beta-hydroxysteroid dehydrogenase X deficiency), FKBP14 (Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss; EDSKMH) and ROGDI (Kohlschutter-Tonz syndrome). These genes have been selected because of our specific research interests in these rare and metabolic diseases. The aim of the database was to include all identified individuals with variants in these specific genes. Identical genotypes are listed multiple times if they were found in several patients, phenotypic descriptions and biochemical data are included as detailed as possible in view also of validating the proposed pathogenicity of these genotypes. For DHCR7 genetic modifier data (maternal APOE and ABCA1 genotypes) is also included. Databases are available at http://databases.lovd.nl/shared/genes and will be updated based on periodic literature reviews and submitted reports. PMID- 25111119 TI - Preparation and in vitro-in vivo evaluation of ofloxacin loaded ophthalmic nano structured lipid carriers modified with chitosan oligosaccharide lactate for the treatment of bacterial keratitis. AB - The objective of this study was to explore the potential of the nanostructured lipid carriers (NLCs) modified with chitosan oligosaccharide lactate (COL) for topical ocular application. Ofloxacin (OFX) loaded NLCs were prepared by microemulsion or high shear homogenization methods. For combination of NLCs Compritol HD5 ATO was used as solid lipid, oleic acid as liquid lipid, Tween 80 as surfactant, ethanol as co-surfactant. The optimum NLCs was modified with 0.75% COL. The properties of NLCs in the absence or presence of OFX (0.3%) were characterized as zeta potential, particle size, viscosity and pH, TEM, drug loading, encapsulation efficiency and anti-microbial properties. Ex-vivo penetration/permeation studies were performed with rabbit cornea in Franz diffusion cells. The penetration rate of OFX from NM-COL4OFX and NH-COL4OFX were significantly higher than commercial solution. Based on the selected formulations, in vivo tests were carried out by eye-drop instillation of NLCs in rabbit. The addition of COL improved the preocular residence time, controlled the drug release and enhanced the corneal bioavailability. In conclusion, OFX COL modified NLCs prepared by high shear homogenization method could be offered as a promising strategy for ocular drug delivery. PMID- 25111120 TI - Effects of information processing speed on learning, memory, and executive functioning in people living with HIV/AIDS. AB - INTRODUCTION: It is unclear whether or to what degree literacy, aging, and other neurologic abnormalities relate to cognitive deficits among people living with HIV/AIDS in the combined antiretroviral therapy (CART) era. The primary aim of this study was to simultaneously examine the association of age, HIV-associated motor abnormalities, major depressive disorder, and reading level with information processing speed, learning, memory, and executive functions, and to determine whether processing speed mediated any of the relationships between cognitive and noncognitive variables. METHOD: Participants were 186 racially and ethnically diverse men and women living with HIV/AIDS who underwent comprehensive neurological, neuropsychological, and medical evaluations. Structural equation modeling was utilized to assess the extent to which information processing speed mediated the relationship between age, motor abnormalities, major depressive disorder, and reading level with other cognitive abilities. RESULTS: Age, motor dysfunction, reading level, and current major depressive disorder were all significantly associated with information processing speed. Information processing speed fully mediated the effects of age on learning, memory, and executive functioning and partially mediated the effect of major depressive disorder on learning and memory. The effect of motor dysfunction on learning and memory was fully mediated by processing speed. CONCLUSIONS: These findings provide support for information processing speed as a primary deficit, which may account, at least in part, for many of the other cognitive abnormalities recognized in complex HIV/AIDS populations. The association of age and information processing speed may account for HIV/aging synergies in the generation of CART-era cognitive abnormalities. PMID- 25111121 TI - The effects of fructose-containing sugars on weight, body composition and cardiometabolic risk factors when consumed at up to the 90th percentile population consumption level for fructose. AB - The American Heart Association (AHA) and World Health Organization (WHO) have recommended restricting calories from added sugars at lower levels than the Institute of Medicine (IOM) recommendations, which are incorporated in the Dietary Guidelines for Americans 2010 (DGAs 2010). Sucrose (SUC) and high fructose corn syrup (HFCS) have been singled out for particular concern, because of their fructose content, which has been specifically implicated for its atherogenic potential and possible role in elevating blood pressure through uric acid-mediated endothelial dysfunction. This study explored the effects when these sugars are consumed at typical population levels up to the 90th percentile population consumption level for fructose. Three hundred fifty five overweight or obese individuals aged 20-60 years old were placed on a eucaloric diet for 10 weeks, which incorporated SUC- or HFCS-sweetened, low-fat milk at 8%, 18% or 30% of calories. There was a slight change in body weight in the entire cohort (169.1 +/- 30.6 vs. 171.6 +/- 31.8 lbs, p < 0.01), a decrease in HDL (52.9 +/- 12.2 vs. 52.0 +/- 13.9 mg/dL, p < 0.05) and an increase in triglycerides (104.1 +/- 51.8 vs. 114.1 +/- 64.7 mg/dL, p < 0.001). However, total cholesterol (183.5 +/- 42.8 vs. 184.4 mg/dL, p > 0.05), LDL (110.3 +/- 32.0 vs. 110.5 +/- 38.9 mg/dL, p > 0.05), SBP (109.4 +/- 10.9 vs. 108.3 +/- 10.9 mmHg, p > 0.05) and DBP (72.1 +/- 8.0 vs. 71.3 +/- 8.0 mmHg, p > 0.05) were all unchanged. In no instance did the amount or type of sugar consumed affect the response to the intervention (interaction p > 0.05). These data suggest that: (1) when consumed as part of a normal diet, common fructose-containing sugars do not raise blood pressure, even when consumed at the 90th percentile population consumption level for fructose (five times the upper level recommended by the AHA and three times the upper level recommended by WHO); (2) changes in the lipid profile are mixed, but modest. PMID- 25111122 TI - Nutrient intake in Italian infants and toddlers from North and South Italy: the Nutrintake 636 study. AB - We performed a cross-sectional study to compare the intake of energy, macronutrients, fiber, sodium and iron and the anthropometric status of infants and toddlers living in North (Milano) and South Italy (Catania). Nutrient intake was evaluated using a 7-day weighed food record. Out of 400 planned children aged 6 to 36 months, 390 (98%) were recruited, 189 in Milano and 201 in Catania. The mean (standard deviation) age was 17 (9) months in Milano and 17 (10) months in Catania. Anthropometry, energy intake and macronutrient intake were similar in Milano and Catania. However, iron intake was 27% lower and fiber intake 16% higher in Milano than in Catania. Despite normal anthropometry and energy intake, in the pooled sample there was a high intake of proteins, simple carbohydrates, saturated fats and sodium, and a low intake of iron and fiber compared to Italian reference values. This is the first study to report the macro- and micro-nutrient intake of children aged <12 months using the 7-day weighed food record and one of the very few studies that have employed such reference method in children from the general population. PMID- 25111124 TI - Parasitic myoma in women after laparoscopic myomectomy: A late sequela of morcellation? PMID- 25111123 TI - Dietary fructose reduction improves markers of cardiovascular disease risk in Hispanic-American adolescents with NAFLD. AB - Nonalcoholic fatty liver disease (NAFLD) is now thought to be the most common liver disease worldwide. Cardiovascular complications are a leading cause of mortality in NAFLD. Fructose, a common nutrient in the westernized diet, has been reported to be associated with increased cardiovascular risk, but its impact on adolescents with NAFLD is not well understood. We designed a 4-week randomized, controlled, double-blinded beverage intervention study. Twenty-four overweight Hispanic-American adolescents who had hepatic fat >8% on imaging and who were regular consumers of sweet beverages were enrolled and randomized to calorie matched study-provided fructose only or glucose only beverages. After 4 weeks, there was no significant change in hepatic fat or body weight in either group. In the glucose beverage group there was significantly improved adipose insulin sensitivity, high sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL) oxidation. These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis. Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials. PMID- 25111127 TI - Dioscin inhibits colon tumor growth and tumor angiogenesis through regulating VEGFR2 and AKT/MAPK signaling pathways. AB - Dioscin has shown cytotoxicity against cancer cells, but its in vivo effects and the mechanisms have not elucidated yet. The purpose of the current study was to assess the antitumor effects and the molecular mechanisms of dioscin. We showed that dioscin could inhibit tumor growth in vivo and has no toxicity at the test condition. The growth suppression was accompanied by obvious blood vessel decrease within solid tumors. We also found dioscin treatment inhibited the proliferation of cancer and endothelial cell lines, and most sensitive to primary cultured human umbilical vein endothelial cells (HUVECs). What's more, analysis of HUVECs migration, invasion, and tube formation exhibited that dioscin has significantly inhibitive effects to these actions. Further analysis of blood vessel formation in the matrigel plugs indicated that dioscin could inhibit VEGF induced blood vessel formation in vivo. We also identified that dioscin could suppress the downstream protein kinases of VEGFR2, including Src, FAK, AKT and Erk1/2, accompanied by the increase of phosphorylated P38MAPK. The results potently suggest that dioscin may be a potential anticancer drug, which efficiently inhibits angiogenesis induced by VEGFR2 signaling pathway as well as AKT/MAPK pathways. PMID- 25111129 TI - Crossover between entropic and interfacial elasticity and osmotic pressure in uniform disordered emulsions. AB - We develop a simple predictive model of the osmotic pressure Pi and linear shear elastic modulus G of uniform disordered emulsions that includes energetic contributions from entropy and interfacial deformation. This model yields a smooth crossover between an entropically dominated G ~ kBT/a(3) for droplet volume fractions phi below a jamming threshold for spheres, phic, and an interfacially dominated G ~ sigma/a for phi above phic, where a and sigma are the undeformed radius and interfacial tension, respectively, of a droplet and T is the temperature. We show that this model reduces to the known phi-dependent jamming behavior G(phi) ~ (sigma/a)phi(phi - phic) as T -> 0 for phi > phic of disordered uniform emulsions, and it also produces the known divergence for disordered hard spheres G(phi) ~ (kBT/a(3))phi/(phic - phi) for phi < phic when sigma -> infinity. We compare predictions of this model to data for disordered uniform microscale emulsion droplets, corrected for electrostatic repulsions. The smooth crossover captures the observed trends in G and Pi below phic better than existing analytic models of disordered emulsions, which do not make predictions below phic. Moreover, the model predicts that entropic contributions to the shear modulus can become more significant for nanoemulsions as compared to microscale emulsions. PMID- 25111128 TI - Is bisphenol S a safe substitute for bisphenol A in terms of metabolic function? An in vitro study. AB - As bisphenol A (BPA) has been shown to induce adverse effects on human health, especially through the activation of endocrine pathways, it is about to be withdrawn from the European market and replaced by analogues such as bisphenol S (BPS). However, toxicological data on BPS is scarce, and so it is necessary to evaluate the possible effects of this compound on human health. We compared the effect of BPA and BPS on obesity and hepatic steatosis processes using low doses in the same range as those found in the environment. Two in vitro models were used, the adipose cell line 3T3-L1 and HepG2 cells, representative of hepatic functions. We analyzed different parameters such as lipid and glucose uptakes, lipolysis, leptin production and the modulation of genes involved in lipid metabolism and energy balance. BPA and BPS induced an increase in the lipid content in the 3T3-L1 cell line and more moderately in the hepatic cells. We also observed a decrease in lipolysis after bisphenol treatment of adipocytes, but only BPS was involved in the increase in glucose uptake and leptin production. These latter effects could be linked to the modulation of SREBP-1c, PPARgamma, aP2 and ERRalpha and gamma genes after exposure to BPA, whereas BPS seems to target the PGC1alpha and the ERRgamma genes. The findings suggest that both BPA and BPS could be involved in obesity and steatosis processes, but through two different metabolic pathways. PMID- 25111131 TI - Current issues of RNAi therapeutics delivery and development. AB - 12 years following the discovery of the RNAi mechanism in Man, a number of RNAi therapeutics development candidates have emerged with profiles suggesting that they could become drugs of significant medical importance for diseases like TTR amyloidosis, HBV, solid cancers, and hemophilia. Despite this robust progress, the perception of RNAi therapeutics has been on a roller-coaster ride driven not only by science, but also regulatory trends, the stock markets, and Big Pharma business development decisions [1]. This presentation provides an update on the current state of RNAi therapeutics development with a particular focus on what RNAi delivery can achieve today and key challenges to be overcome to expand therapeutic opportunities. The delivery of RNAi triggers to disease-relevant cell types clearly represents the rate-limiting factor in broadly expanding the applicability of RNAi therapeutics. Today, with at least 3 delivery options (lipid nanoparticles/LNPs, GalNAc-siRNA conjugates, Dynamic PolyConjugates/DPCs) for which profound gene knockdowns have been demonstrated in non-human primates and in the clinic, RNAi therapeutics should in principle be able to address most diseases related to gene expression in the liver. Given the central importance of the liver in systemic physiology, this already represents a significant therapeutic and commercial opportunity rivaling that of e.g. monoclonal antibodies. Beyond the liver, there is a reason to believe that current RNAi therapeutics technologies can address a number of solid tumors (e.g. LNPs), diseases of the eye (e.g. self-delivering RNAi triggers) as well as diseases involving the respiratory epithelium (e.g. aerosolized LNPs), certain phagocytic cells (LNPs), hematopoietic stem cells and their progeny (lentiviral DNA-directed RNAi), vascular endothelial cells (cationic lipoplexes), and certain cell types in the kidney (self-delivering RNAi triggers, DPCs; Table 1). Despite this success, there has been a sense that the applications of RNAi therapeutics are rather limited. This is largely based on the observation that the biodistribution of RNAi formulations is typically more limited compared to small molecules and oral administration is not possible with current technologies. Similarly, the utility of a given RNAi formulation is limited to a few cell types and tissues at most and a universal delivery strategy should remain elusive for the foreseeable future. Therefore, to further expand on the therapeutic utility and patient convenience of RNAi, it is important to overcome a number of delivery-related technical and scientific challenges which will be discussed in this presentation. For systemic applications, these include the necessity for extended blood circulation times, vascular escape (probably the most rewarding inquiry currently), tissue penetration, cellular uptake, and escape into the cytoplasm. In terms of safety, it is important that these formulations do not accumulate in the body, do not cause excessive off-targeting due to 'chemical stickiness' (often useful for purposes of biodistribution), and overcome the physical/biological barriers in a controlled manner. The time for realizing the therapeutic potential of RNAi has come. At the same time, it is important to lay the foundations for the next leg of value creation by overcoming the challenges of delivering RNAi to new cell types. Based on results from exploratory research, the renewed interest in RNAi therapeutics and capital infusion, there is a reason to be optimistic that this can be achieved. PMID- 25111130 TI - Microparticle-loaded neonatal porcine Sertoli cells for cell-based therapeutic and drug delivery system. AB - Neonatal porcine Sertoli cells (NPSC) are immune privileged cells showing innate phagocytic and antibacterial activities. NPSC have been shown capable of immunoaltering the body's response and possess lung homing capacity. These properties encourage investigation of NPSC as functional components of cell-based therapeutic protocols to treat lung infections and related complications. In this work, for the first time, NPSC were tailored to carry an antibiotic drug loaded into poly(d,l lactic) acid microparticles (MP). A loading protocol was developed, which afforded 30% drug uptake and high stability over time, with little or no effects on NPSC viability, morphology, reactive oxygen species production and DNA integrity. FSH receptor integrity, and TGFbeta (transforming growth factor beta) and AMH (anti-Mullerian hormone) expressions were unchanged after 1month of cryopreservation. Protein tyrosine kinase activation due to phagocytosis may have had resulted in changes in inhibin B expression. The activity of MP-loaded or NPSC alone against Pseudomonas aeruginosa was maintained throughout 1month of storage. NPSC couple an innate antibacterial activity with the capacity to embody drug loaded MP. We showed for the first time that engineered NPSC can be cryopreserved with no loss of their basic properties, thereby possibly representing a novel approach for cell-based therapeutic and drug delivery system. PMID- 25111132 TI - Origin of cardiovascular risk in overweight preschool children: a cohort study of cardiometabolic risk factors at the onset of obesity. AB - IMPORTANCE: To date, the relationship among adiposity, insulin resistance, and cardiovascular risk factors at the onset of overweight or obesity has been unexplored. OBJECTIVES: To assess whether insulin resistance and metabolic abnormalities are detectable at the onset of obesity and to unravel the interplay among adiposity, insulin resistance, and other such abnormalities. DESIGN, SETTING, AND PARTICIPANTS: The Origin of Cardiovascular Risk in Overweight Preschool Children cohort study aimed to evaluate at the onset of obesity in preschool children the prevalence of metabolic abnormalities, including hypertension, dyslipidemia, impaired carbohydrate metabolism, and nonalcoholic fatty liver disease. Between July 1, 2011, and July 30, 2012, in the Rome municipality, 13 family pediatricians enrolled healthy children (age range, 2.0 5.8 years) in the study during their routine practice of growth monitoring. Clinical medical records of 5729 children were reviewed; 597 children manifested new-onset overweight or obesity as their body mass index changed from normal weight to overweight or obesity in the previous 12 months according to the International Obesity Task Force classification. Of them, 219 were studied. MAIN OUTCOMES AND MEASURES: Patients with new-onset overweight or obesity underwent clinical laboratory testing, including oral glucose tolerance test, and ultrasonographic investigations of fatty liver and intimal medial thickness of the common carotid arteries, subcutaneous adipose tissue, and visceral adipose tissue. The homeostatic assessment model algorithm-insulin resistance was calculated. RESULTS: Among the entire population (n = 5729), overweight increased from 7.0% at 2.0 years to 16.9% at 5.8 years, with corresponding figures of 1.1% to 2.9% for obesity. In total, 597 overweight or obese children (10.4%) were identified, and 219 of them (36.7%) were studied. Among the latter, 86 patients (39.3%) had at least 1 metabolic abnormality. Hypertension was diagnosed in 29 patients (13.2%), dyslipidemia in 55 patients (25.1%), impaired fasting glucose level in 7 patients (3.2%), and glucose intolerance in 6 patients (2.7%). Nonalcoholic fatty liver disease was diagnosed in 68 patients (31.1%). CONCLUSIONS AND RELEVANCE: Cardiometabolic risk factors, including fatty liver, are detectable in preschoolers at the onset of overweight or obesity, despite short-term exposure to excess weight and reduced insulin sensitivity. Our findings suggest the need to screen for cardiometabolic abnormalities at an earlier age than is now recommended. PMID- 25111133 TI - New members of fluorescent 1,8-naphthyridine-based BF2 compounds: selective binding of BF2 with terminal bidentate N^N^O and N^C^O groups and tunable spectroscopy properties. AB - Intensely luminescent 1,8-naphthyridine-BF2 complexes 1-9 containing terminal bidentate N^N^O and/or N^C^O groups are synthesized and structurally characterized by X-ray diffraction, electrospray ionization mass spectrometry, (1)H and (19)F NMR spectroscopy and elemental analysis. Complexes 1-4 are synthesized from 2-acetamino-1,8-naphthyridine derivatives by a facile route. Selective bonding modes and the chemical stability of complexes 5 and 6 obtained by reacting BF3.Et2O with 1,8-naphthyridine derivatives bearing dual-functional groups (N^C^O and N^N^O) are investigated by crystal structure analysis and time dependent density functional theory calculations. The products containing a BF2 core bound to a N^C^O chelating group are energetically favorable and can expand the range of derivatives by substitution at the 2-position. In this regard, a free -NH2 group at the 2-position of complex 7 obtained from 5 can be functionalized under a variety of pH conditions to generate complexes 8 and 9, which bear flexible coordination arms that can be used to recognize certain transition metals. The photophysical properties of the complexes are examined in solution and solid state at room temperature. Compared with those of the starting naphthyridine-based compounds, the naphthyridine-BF2 complexes display desirable light-absorbing properties and intense solution and solid-state emission with large Stokes shifts. Complex 4 in solution exhibited an emission quantum yield of 0.98. In complexes 5-9, the binding sites for the BF2 core change from N^N^O to N^C^O, which leads to red shifts of absorption and emission, excellent chemical stability and high emission quantum yields. PMID- 25111134 TI - Deterministic coupling of a single silicon-vacancy color center to a photonic crystal cavity in diamond. AB - Deterministic coupling of single solid-state emitters to nanocavities is the key for integrated quantum information devices. We here fabricate a photonic crystal cavity around a preselected single silicon-vacancy color center in diamond and demonstrate modification of the emitters internal population dynamics and radiative quantum efficiency. The controlled, room-temperature cavity coupling gives rise to a resonant Purcell enhancement of the zero-phonon transition by a factor of 19, coming along with a 2.5-fold reduction of the emitter's lifetime. PMID- 25111135 TI - Radiofrequency ablation for the treatment of gastric antral vascular ectasia. AB - BACKGROUND AND STUDY AIMS: The traditional endoscopic treatment for gastric antral vascular ectasia (GAVE) is argon plasma coagulation, but results are not always positive. Radiofrequency ablation (RFA) is a new endoscopic therapy that may be an attractive option for the treatment of GAVE. The aim of this study was to assess the efficacy and safety of RFA for the treatment of GAVE. PATIENTS AND METHODS: This was an open-label, retrospective, case series study. The main outcome measures were number of red blood cell (RBC) packs transfused (transfusion requirement) and hemoglobin concentrations (g/dL) in the 6 months prior to and after RFA. Success was defined as a decrease in transfusion requirement in the 6 months after RFA compared with before treatment. RESULTS: A total of 24 patients underwent a mean of 1.8 +/- 0.8 RFA sessions. No complications were reported. One patient was referred for additional argon plasma coagulation during follow-up. The mean number of RBC packs decreased in all 23 transfusion-dependent patients, from a mean of 10.6 +/- 12.1 during the 6 months prior to RFA, to a mean of 2.5 +/- 5.9 during the 6 months after RFA treatment (P < 0.001), and 15 patients (65.2 %) were weaned off transfusions completely. An increase in the hemoglobin concentration was reported in all patients after RFA (from 6.8 +/- 1.4 g/dL to 9.8 +/- 1.8 g/dL; P < 0.001). CONCLUSION: RFA for the treatment of GAVE seems feasible and safe, and significantly reduced the need for RBC transfusion and increased the hemoglobin level in this retrospective case series. PMID- 25111136 TI - Deep biopsy via endoscopic submucosal dissection in upper gastrointestinal subepithelial tumors: a prospective study. AB - BACKGROUND AND STUDY AIMS: Preoperative pathological diagnosis may improve clinical management decisions in patients with upper gastrointestinal subepithelial tumors (SETs). The aims of this study were to evaluate the diagnostic yield of deep biopsy via an endoscopic submucosal dissection (ESD) technique, the complications associated with the procedure, and the impact on management of patients with upper gastrointestinal SETs. PATIENTS AND METHODS: A total of 68 patients with SETs in the stomach or esophagus were voluntarily assigned to two groups. One group underwent endoscopic ultrasound (EUS) and endoscopic deep biopsy using the ESD technique (40 patients), and the other group (28 patients) underwent surgical resection after EUS without obtaining preoperative pathological diagnosis, in accordance with accepted clinical management algorithms. RESULTS: The diagnostic yield of deep biopsy was 90 % (36/40). The results of deep biopsy changed the treatment plans in 14/40 patients (35 %). One patient with lymphoepithelial carcinoma was scheduled for surgical resection, and 13 patients with benign SETs of diameter >= 2 cm avoided surgery. Of the 28 patients who underwent surgical resection without preoperative pathological diagnosis, 12 (42.9 %) were confirmed to have benign lesions. The mean procedure time for deep biopsy was 13.7 minutes. There were no procedure related complications in the deep biopsy group. CONCLUSIONS: Deep biopsy by the ESD technique is a safe, high-yield, diagnostic method in patients with upper gastrointestinal SETs. Pathologic confirmation could improve clinical decision making in the management of patients with upper gastrointestinal SETs. CLINICAL TRIAL REGISTRATION: NCT 01993199. PMID- 25111138 TI - Novel intramedullary-fixation technique for long bone fragility fractures using bioresorbable materials. AB - Almost all of the currently available fracture fixation devices for metaphyseal fragility fractures are made of hard metals, which carry a high risk of implant related complications such as implant cutout in severely osteoporotic patients. We developed a novel fracture fixation technique (intramedullary-fixation with biodegradable materials; IM-BM) for severely weakened long bones using three different non-metallic biomaterials, a poly(l-lactide) (PLLA) woven tube, a nonwoven polyhydroxyalkanoates (PHA) fiber mat, and an injectable calcium phosphate cement (CPC). The purpose of this work was to evaluate the feasibility of IM-BM with mechanical testing as well as with an animal experiment. To perform mechanical testing, we fixed two longitudinal acrylic pipes with four different methods, and used them for a three-point bending test (N = 5). The three-point bending test revealed that the average fracture energy for the IM-BM group (PLLA + CPC + PHA) was 3 times greater than that of PLLA + CPC group, and 60 to 200 times greater than that of CPC + PHA group and CPC group. Using an osteoporotic rabbit distal femur incomplete fracture model, sixteen rabbits were randomly allocated into four experimental groups (IM-BM group, PLLA + CPC group, CPC group, Kirschner wire (K-wire) group). No rabbit in the IM-BM group suffered fracture displacement even under full weight bearing. In contrast, two rabbits in the PLLA + CPC group, three rabbits in the CPC group, and three rabbits in the K wire group suffered fracture displacement within the first postoperative week. The present work demonstrated that IM-BM was strong enough to reinforce and stabilize incomplete fractures with both mechanical testing and an animal experiment even in the distal thigh, where bone is exposed to the highest bending and torsional stresses in the body. IM-BM can be one treatment option for those with severe osteoporosis. PMID- 25111137 TI - Extinction risks and the conservation of Madagascar's reptiles. AB - BACKGROUND: An understanding of the conservation status of Madagascar's endemic reptile species is needed to underpin conservation planning and priority setting in this global biodiversity hotspot, and to complement existing information on the island's mammals, birds and amphibians. We report here on the first systematic assessment of the extinction risk of endemic and native non-marine Malagasy snakes, lizards, turtles and tortoises. METHODOLOGY/PRINCIPAL FINDINGS: Species range maps from The IUCN Red List of Threatened Species were analysed to determine patterns in the distribution of threatened reptile species. These data, in addition to information on threats, were used to identify priority areas and actions for conservation. Thirty-nine percent of the data-sufficient Malagasy reptiles in our analyses are threatened with extinction. Areas in the north, west and south-east were identified as having more threatened species than expected and are therefore conservation priorities. Habitat degradation caused by wood harvesting and non-timber crops was the most pervasive threat. The direct removal of reptiles for international trade and human consumption threatened relatively few species, but were the primary threats for tortoises. Nine threatened reptile species are endemic to recently created protected areas. CONCLUSIONS/SIGNIFICANCE: With a few alarming exceptions, the threatened endemic reptiles of Madagascar occur within the national network of protected areas, including some taxa that are only found in new protected areas. Threats to these species, however, operate inside and outside protected area boundaries. This analysis has identified priority sites for reptile conservation and completes the conservation assessment of terrestrial vertebrates in Madagascar which will facilitate conservation planning, monitoring and wise-decision making. In sharp contrast with the amphibians, there is significant reptile diversity and regional endemism in the southern and western regions of Madagascar and this study highlights the importance of these arid regions to conserving the island's biodiversity. PMID- 25111139 TI - The strong selective sweep candidate gene ADRA2C does not explain domestication related changes in the stress response of chickens. AB - Analysis of selective sweeps to pinpoint causative genomic regions involved in chicken domestication has revealed a strong selective sweep on chromosome 4 in layer chickens. The autoregulatory alpha-adrenergic receptor 2C (ADRA2C) gene is the closest to the selective sweep and was proposed as an important gene in the domestication of layer chickens. The ADRA2C promoter region was also hypermethylated in comparison to the non-selected ancestor of all domesticated chicken breeds, the Red Junglefowl, further supporting its relevance. In mice the receptor is involved in the fight-or-flight response as it modulates epinephrine release from the adrenals. To investigate the involvement of ADRA2C in chicken domestication, we measured gene expression in the adrenals and radiolabeled receptor ligand in three brain regions comparing the domestic White Leghorn strain with the wild ancestor Red Junglefowl. In adrenals ADRA2C was twofold greater expressed than the related receptor gene ADRA2A, indicating that ADRA2C is the predominant modulator of epinephrine release but no strain differences were measured. In hypothalamus and amygdala, regions associated with the stress response, and in striatum, receptor binding pIC50 values ranged between 8.1-8.4, and the level was not influenced by the genotyped allele. Because chicken strains differ in morphology, physiology and behavior, differences attributed to a single gene may be lost in the noise caused by the heterogeneous genetic background. Therefore an F10 advanced intercross strain between White Leghorn and Red Junglefowl was used to investigate effects of ADRA2C alleles on fear related behaviors and fecundity. We did not find compelling genotype effects in open field, tonic immobility, aerial predator, associative learning or fecundity. Therefore we conclude that ADRA2C is probably not involved in the domestication of the stress response in chicken, and the strong selective sweep is probably caused by selection of some unknown genetic element in the vicinity of the gene. PMID- 25111140 TI - Can gas replace protein function? CO abrogates the oxidative toxicity of myoglobin. AB - Outside their cellular environments, hemoglobin (Hb) and myoglobin (Mb) are known to wreak oxidative damage. Using haptoglobin (Hp) and hemopexin (Hx) the body defends itself against cell-free Hb, yet mechanisms of protection against oxidative harm from Mb are unclear. Mb may be implicated in oxidative damage both within the myocyte and in circulation following rhabdomyolysis. Data from the literature correlate rhabdomyolysis with the induction of Heme Oxygenase-1 (HO 1), suggesting that either the enzyme or its reaction products are involved in oxidative protection. We hypothesized that carbon monoxide (CO), a product, might attenuate Mb damage, especially since CO is a specific ligand for heme iron. Low density lipoprotein (LDL) was chosen as a substrate in circulation and myosin (My) as a myocyte component. Using oxidation targets, LDL and My, the study compared the antioxidant potential of CO in Mb-mediated oxidation with the antioxidant potential of Hp in Hb-mediated oxidation. The main cause of LDL oxidation by Hb was found to be hemin which readily transfers from Hb to LDL. Hp prevented heme transfer by sequestering hemin within the Hp-Hb complex. Hemin barely transferred from Mb to LDL, and oxidation appeared to stem from heme iron redox in the intact Mb. My underwent oxidative crosslinking by Mb both in air and under N2. These reactions were fully arrested by CO. The data are interpreted to suit several circumstances, some physiological, such as high muscle activity, and some pathological, such as rhabdomyolysis, ischemia/reperfusion and skeletal muscle disuse atrophy. It appear that CO from HO-1 attenuates damage by temporarily binding to deoxy-Mb, until free oxygen exchanges with CO to restore the equilibrium. PMID- 25111141 TI - Tick surveillance for relapsing fever spirochete Borrelia miyamotoi in Hokkaido, Japan. AB - During 2012-2013, a total of 4325 host-seeking adult ticks belonging to the genus Ixodes were collected from various localities of Hokkaido, the northernmost island of Japan. Tick lysates were subjected to real-time PCR assay to detect borrelial infection. The assay was designed for specific detection of the Relapsing fever spirochete Borrelia miyamotoi and for unspecific detection of Lyme disease-related spirochetes. Overall prevalence of B. miyamotoi was 2% (71/3532) in Ixodes persulcatus, 4.3% (5/117) in Ixodes pavlovskyi and 0.1% (1/676) in Ixodes ovatus. The prevalence in I. persulcatus and I. pavlovskyi ticks were significantly higher than in I. ovatus. Co-infections with Lyme disease-related spirochetes were found in all of the tick species. During this investigation, we obtained 6 isolates of B. miyamotoi from I. persulcatus and I. pavlovskyi by culture in BSK-M medium. Phylogenetic trees of B. miyamotoi inferred from each of 3 housekeeping genes (glpQ, 16S rDNA, and flaB) demonstrated that the Hokkaido isolates were clustered with Russian B. miyamotoi, but were distinguishable from North American and European B. miyamotoi. A multilocus sequence analysis using 8 genes (clpA, clpX, nifS, pepX, pyrG, recG, rplB, and uvrA) suggested that all Japanese B. miyamotoi isolates, including past isolates, were genetically clonal, although these were isolated from different tick and vertebrate sources. From these results, B. miyamotoi-infected ticks are widely distributed throughout Hokkaido. Female I. persulcatus are responsible for most human tick-bites, thereby I. persulcatus is likely the most important vector of indigenous relapsing fever from tick bites in Hokkaido. PMID- 25111142 TI - Children with chronic suppurative lung disease have a reduced capacity to synthesize interferon-gamma in vitro in response to non-typeable Haemophilus influenzae. AB - Chronic suppurative lung disease (CSLD) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. The aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly isolated from the airways in CSLD, we examined immune responses to this organism in 80 age-stratified children with CSLD and compared their responses with 51 healthy control children. Cytokines involved in the generation and control of inflammation (IFN-gamma, IL-13, IL-5, IL-10 at 72 hours and TNFalpha, IL-6, IL-10 at 24 hours) were measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. We also measured circulating IgG subclass antibodies (IgG1 and IgG4) to two H. influenzae outer membrane proteins, P4 and P6. The most notable finding was that PBMC from children with CSLD produced significantly less IFN-gamma in response to NTHi than healthy control children whereas mitogen induced IFN-gamma production was similar in both groups. Overall there were minor differences in innate and humoral immune responses between CSLD and control children. This study demonstrates that children with chronic suppurative lung disease have an altered systemic cell-mediated immune response to NTHi in vitro. This deficient IFN-gamma response may contribute to increased susceptibility to NTHi infections and the pathogenesis of CSLD in children. PMID- 25111144 TI - Single-channel prototype terahertz endoscopic system. AB - We demonstrate the design and development of an innovative single-channel terahertz (THz) prototype endoscopic imaging system based on flexible metal coated THz waveguides and a polarization specific detection technique. The continuous-wave (CW) THz imaging system utilizes a single channel to transmit and collect the reflected intrinsic THz signal from the sample. Since the prototype system relies on a flexible waveguide assembly that is small enough in diameter, it can be readily integrated with a conventional optical endoscope. This study aims to show the feasibility of waveguide enabled THz imaging. We image various objects in transmission and reflection modes. We also image normal and cancerous colonic tissues in reflectance mode using a polarization specific imaging technique. The resulting cross-polarized THz reflectance images showed contrast between normal and cancerous colonic tissues at 584 GHz. The level of contrast observed using endoscopic imaging correlates well with contrast levels observed in ex vivo THz reflectance studies of colon cancer. This indicates that the single-channel flexible waveguide-based THz endoscope presented here represents a significant step forward in clinical endoscopic application of THz technology to aid in in vivo cancer screening. PMID- 25111143 TI - Characterization of newly isolated lytic bacteriophages active against Acinetobacter baumannii. AB - Based on genotyping and host range, two newly isolated lytic bacteriophages, myovirus vB_AbaM_Acibel004 and podovirus vB_AbaP_Acibel007, active against Acinetobacter baumannii clinical strains, were selected from a new phage library for further characterization. The complete genomes of the two phages were analyzed. Both phages are characterized by broad host range and essential features of potential therapeutic phages, such as short latent period (27 and 21 min, respectively), high burst size (125 and 145, respectively), stability of activity in liquid culture and low frequency of occurrence of phage-resistant mutant bacterial cells. Genomic analysis showed that while Acibel004 represents a novel bacteriophage with resemblance to some unclassified Pseudomonas aeruginosa phages, Acibel007 belongs to the well-characterized genus of the Phikmvlikevirus. The newly isolated phages can serve as potential candidates for phage cocktails to control A. baumannii infections. PMID- 25111145 TI - Micrometric precision of prosthetic dental crowns obtained by optical scanning and computer-aided designing/computer-aided manufacturing system. AB - The current study evaluated prosthetic dental crowns obtained by optical scanning and a computer-aided designing/computer-aided manufacturing system using micro computed tomography to compare the marginal fit. The virtual models were obtained with four different scanning surfaces: typodont (T), regular impressions (RI), master casts (MC), and powdered master casts (PMC). Five virtual models were obtained for each group. For each model, a crown was designed on the software and milled from feldspathic ceramic blocks. Micro-CT images were obtained for marginal gap measurements and the data were statistically analyzed by one-way analysis of variance followed by Tukey's test. The mean vertical misfit was T = 62.6 +/- 65.2 MUm ; MC = 60.4 +/- 38.4 MUm; PMC = 58.1 +/- 38.0 MUm, and RI = 89.8 +/- 62.8 MUm. Considering a percentage of vertical marginal gap of up to 75 MUm, the results were T = 71.5%, RI = 49.2%, MC = 69.6%, and PMC = 71.2%. The percentages of horizontal overextension were T = 8.5%, RI = 0%, MC = 0.8%, and PMC = 3.8%. Based on the results, virtual model acquisition by scanning the typodont (simulated mouth) or MC, with or without powder, showed acceptable values for the marginal gap. The higher result of marginal gap of the RI group suggests that it is preferable to scan this directly from the mouth or from MC. PMID- 25111146 TI - Thermoreversible gel lubricants through universal supramolecular assembly of a nonionic surfactant in a variety of base lubricating liquids. AB - The present paper investigates a new type of thermoreversible gel lubricant obtained by supramolecular assembly of low-molecular-weight organic gelator (LMWG) in different base oils. The LMWG is a nonionic surfactant with polar headgroup and hydrophobic tail that can self-assemble through collective noncovalent intermolecular interactions (H-bonding, hydrophobic interaction) to form fibrous structures and trap base oils (mineral oils, synthetic oils, and water) in the as-formed cavities. The gel lubricants are fully thermoreversible upon heating-up and cooling down and exhibit thixotropic characteristics. This makes them semisolid lubricants, but they behave like oils. The tribological test results disclosed that the LMWG could also effectively reduce friction and wear of sliding pairs compared with base oils without gelator. It is expected that when being used in oil-lubricated components, such as gear, rolling bearing, and so on, gel lubricant may effectively avoid base oil leak and evaporation loss and so is a benefit to operation and lubrication failure for a long time. PMID- 25111149 TI - Knowledge-based libraries for predicting the geometric preferences of druglike molecules. AB - We describe the automated generation of libraries for predicting the geometric preferences of druglike molecules. The libraries contain distributions of molecular dimensions based on crystal structures in the Cambridge Structural Database (CSD). Searching of the libraries is performed in cascade fashion to identify the most relevant distributions in cases where precise structural features are poorly represented by existing crystal structures. The libraries are fully comprehensive for bond lengths, valence angles, and rotamers and produce templates for the large majority of unfused and fused rings. Geometry distributions for rotamers and rings take into account any atom chirality that may be present. Library validation has been performed on a set of druglike molecules whose structures were published after the latest CSD entry contributing to the libraries. Hence, the validation gives a true indication of prediction accuracy. PMID- 25111147 TI - Treatment efficacy for non-cardiovascular chest pain: a systematic review and meta-analysis. AB - BACKGROUND: Non-cardiovascular chest pain (NCCP) leads to impaired quality of life and is associated with a high disease burden. Upon ruling out cardiovascular disease, only vague recommendations exist for further treatment. OBJECTIVES: To summarize treatment efficacy for patients presenting with NCCP. METHODS: Systematic review and meta-analysis. In July 2013, Medline, Web of Knowledge, Embase, EBSCOhost, Cochrane Reviews and Trials, and Scopus were searched. Hand and bibliography searches were also conducted. Randomized controlled trials (RCTs) evaluating non-surgical treatments in patients with NCCP were included. Exclusion criteria were poor study quality and small sample size (<10 patients per group). RESULTS: Thirty eligible RCT's were included. Most studies assessed PPI efficacy for gastroesophageal reflux disorders (GERD, n = 10). Two RCTs included musculoskeletal chest pain, seven psychotropic drugs, and eleven various psychological interventions. Study quality was high in five RCTs and acceptable in 25. PPI treatment in patients with GERD (5 RCTs, 192 patients) was more effective than placebo [pooled OR 11.7 (95% CI 5.5 to 25.0, heterogeneity I2 = 6.1%)]. The pooled OR in GERD negative patients (4 RCTs, 156 patients) was 0.8 (95% CI 0.2 to 2.8, heterogeneity I2 = 50.4%). In musculoskeletal NCCP (2 RCTs, 229 patients) manual therapy was more effective than usual care but not than home exercise [pooled mean difference 0.5 (95% CI -0.3 to 1.3, heterogeneity I2 = 46.2%)]. The findings for cognitive behavioral treatment, serotonin reuptake inhibitors, tricyclic antidepressants were mixed. Most evidence was available for cognitive behavioral treatment interventions. LIMITATIONS: Only a small number of studies were available. CONCLUSIONS: Timely diagnostic evaluation and treatment of the disease underlying NCCP is important. For patients with suspected GERD, high-dose treatment with PPI is effective. Only limited evidence was available for most prevalent diseases manifesting with chest pain. In patients with idiopathic NCCP, treatments based on cognitive behavioral principles might be considered. PMID- 25111151 TI - Axolotls with an under- or oversupply of neural crest can regulate the sizes of their dorsal root ganglia to normal levels. AB - How animals adjust the size of their organs is a fundamental, enduring question in biology. Here we manipulate the amount of neural crest (NC) precursors for the dorsal root ganglia (DRG) in axolotl. We produce embryos with an under- or over supply of pre-migratory NC in order to find out if DRG can regulate their sizes during development. Axolotl embryos are perfectly suitable for this research. Firstly, they are optimal for microsurgical manipulations and tissue repair. Secondly, they possess, unlike most other vertebrates, only one neural crest string located on top of the neural tube. This condition and position enables NC cells to migrate to either side of the embryo and participate in the regulation of NC cell distribution. We show that size compensation of DRG in axolotl occurs in 2 cm juveniles after undersupply of NC (up-regulation) and in 5 cm juveniles after oversupply of NC (down-regulation). The size of DRG is likely to be regulated locally within the DRG and not via adaptations of the pre-migratory NC or during NC cell migration. Ipsi- and contralateral NC cell migration occurs both in embryos with one and two neural folds, and contralateral migration of NC is the only source for contralateral DRG formation in embryos with only one neural fold. Compensatory size increase is accompanied by an increase in cell division of a DRG precursor pool (PCNA+/SOX2-), rather than by DRG neurons or glial cells. During compensatory size decrease, increased apoptosis and reduced proliferation of DRG cells are observed. PMID- 25111152 TI - Chemical preparation of ferroelectric mesoporous barium titanate thin films: drastic enhancement of Curie temperature induced by mesopore-derived strain. AB - Mesoporous barium titanate (BT) thin films are synthesized by a surfactant assisted sol-gel method. The obtained mesoporous BT thin films show enhanced ferroelectricity due to the effective strains induced by mesopores. The Curie temperature (T(c)) of the mesoporous BT reaches approximately 470 degrees C. PMID- 25111153 TI - High interfacial activity of polymers "grafted through" functionalized iron oxide nanoparticle clusters. AB - The mechanism by which polymers, when grafted to inorganic nanoparticles, lower the interfacial tension at the oil-water interface is not well understood, despite the great interest in particle stabilized emulsions and foams. A simple and highly versatile free radical "grafting through" technique was used to bond high organic fractions (by weight) of poly(oligo(ethylene oxide) monomethyl ether methacrylate) onto iron oxide clusters, without the need for catalysts. In the resulting ~1 MUm hybrid particles, the inorganic cores and grafting architecture contribute to the high local concentration of grafted polymer chains to the dodecane/water interface to produce low interfacial tensions of only 0.003 w/v % (polymer and particle core). This "critical particle concentration" (CPC) for these hybrid inorganic/polymer amphiphilic particles to lower the interfacial tension by 36 mN/m was over 30-fold lower than the critical micelle concentration of the free polymer (without inorganic cores) to produce nearly the same interfacial tension. The low CPC is favored by the high adsorption energy (~10(6) kBT) for the large ~1 MUm hybrid particles, the high local polymer concentration on the particles surfaces, and the ability of the deformable hybrid nanocluster cores as well as the polymer chains to conform to the interface. The nanocluster cores also increased the entanglement of the polymer chains in bulk DI water or synthetic seawater, producing a viscosity up to 35,000 cP at 0.01 s(-1), in contrast with only 600 cP for the free polymer. As a consequence of these interfacial and rheological properties, the hybrid particles stabilized oil-in water emulsions at concentrations as low as 0.01 w/v %, with average drop sizes down to 30 MUm. In contrast, the bulk viscosity was low for the free polymer, and it did not stabilize the emulsions. The ability to influence the interfacial activity and rheology of polymers upon grafting them to inorganic particles, including clusters, may be expected to be broadly applicable to stabilization of emulsions and foams. PMID- 25111154 TI - Interplay between cellular activity and three-dimensional scaffold-cell constructs with different foam structure processed by electron beam melting. AB - The cellular activity, biological response, and consequent integration of scaffold-cell construct in the physiological system are governed by the ability of cells to adhere, proliferate, and biomineralize. In this regard, we combine cellular biology and materials science and engineering to fundamentally elucidate the interplay between cellular activity and interconnected three-dimensional foamed architecture obtained by a novel process of electron beam melting and computational tools. Furthermore, the organization of key proteins, notably, actin, vinclulin, and fibronectin, involved in cellular activity and biological functions and relationship with the structure was explored. The interconnected foamed structure with ligaments was favorable to cellular activity that includes cell attachment, proliferation, and differentiation. The primary rationale for favorable modulation of cellular functions is that the foamed structure provided a channel for migration and communication between cells leading to highly mineralized extracellular matrix (ECM) by the differentiating osteoblasts. The filopodial interaction amongst cells on the ligaments was a governing factor in the secretion of ECM, with consequent influence on maturation and mineralization. PMID- 25111156 TI - The introduction of dengue vaccine may temporarily cause large spikes in prevalence. AB - A dengue vaccine is expected to be available within a few years. Once vaccine is available, policy-makers will need to develop suitable policies to allocate the vaccine. Mathematical models of dengue transmission predict complex temporal patterns in prevalence, driven by seasonal oscillations in mosquito abundance. In particular, vaccine introduction may induce a transient period immediately after vaccine introduction where prevalence can spike higher than in the pre vaccination period. These spikes in prevalence could lead to doubts about the vaccination programme among the public and even among decision-makers, possibly impeding the vaccination programme. Using simple dengue transmission models, we found that large transient spikes in prevalence are robust phenomena that occur when vaccine coverage and vaccine efficacy are not either both very high or both very low. Despite the presence of transient spikes in prevalence, the models predict that vaccination does always reduce the total number of infections in the 15 years after vaccine introduction. We conclude that policy-makers should prepare for spikes in prevalence after vaccine introduction to mitigate the burden of these spikes and to accurately measure the effectiveness of the vaccine programme. PMID- 25111157 TI - Enzyme immobilised novel core-shell superparamagnetic nanocomposites for enantioselective formation of 4-(R)-hydroxycyclopent-2-en-1-(S)-acetate. AB - Lipase immobilized novel high surface area core-shell superparamagnetic nanoparticles have been fabricated and used as efficient reusable catalysts for the selective production of pharmaceutically important chiral isomers from meso cyclopent-2-en-1,4-diacetate. PMID- 25111155 TI - An integrative omics strategy to assess the germ cell secretome and to decipher sertoli-germ cell crosstalk in the Mammalian testis. AB - Mammalian spermatogenesis, which takes place in complex testicular structures called seminiferous tubules, is a highly specialized process controlled by the integration of juxtacrine, paracrine and endocrine information. Within the seminiferous tubules, the germ cells and Sertoli cells are surrounded by testicular fluid (TF), which probably contains most of the secreted proteins involved in crosstalk between these cells. It has already been established that germ cells can modulate somatic Sertoli cell function through the secretion of diffusible factors. We studied the germ cell secretome, which was previously considered inaccessible, by analyzing the TF collected by microsurgery in an "integrative omics" strategy combining proteomics, transcriptomics, genomics and interactomics data. This approach identified a set of proteins preferentially secreted by Sertoli cells or germ cells. An interaction network analysis revealed complex, interlaced cell-cell dialog between the secretome and membranome of seminiferous cells, mediated via the TF. We then focused on germ cell-secreted candidate proteins, and we identified several potential interacting partners located on the surface of Sertoli cells. Two interactions, APOH/CDC42 and APP/NGFR, were validated in situ, in a proximity ligation assay (PLA). Our results provide new insight into the crosstalk between germ cells and Sertoli cells occurring during spermatogenesis. Our findings also demonstrate that this "integrative omics" strategy is powerful enough for data mining and highlighting meaningful cell-cell communication events between different types of cells in a complex tissue, via a biological fluid. This integrative strategy could be applied more widely, to gain access to secretomes that have proved difficult to study whilst avoiding the limitations of in vitro culture. PMID- 25111158 TI - Single-victim and serial sexual homicide offenders: differences in crime, paraphilias and personality traits. AB - BACKGROUND: Information on psychopathological characteristics of sexual homicide offenders is scarce. AIMS: To investigate criminal, paraphilic and personality trait differences between serial and single-victim sexual homicide offenders. METHODS: All 73 single-victim and 13 serial sexual homicide offenders presenting within a cohort of 671 men sentenced for sexual crimes between 1994 and 2005 and serving their sentence in one high-security Canadian prison and who consented to interview were assessed and compared on their offending patterns, personality pathology and paraphilic behaviours. RESULTS: Serial sexual homicide offenders were more likely than the single offenders to report deviant sexual fantasies, having selected victims with distinctive characteristics, to have targeted strangers, structured premeditation and/or verbal humiliation of their victims during the offences. Personality pathology, defined by at least two Diagnostic and Statistical Manual of Mental Disorders IV criteria for personality disorder, was common in both groups, but the serial offenders were more likely to have narcissistic, schizoid and/or obsessive-compulsive traits; they were also more likely to engage in sexual masochism, partialism, homosexual paedophilia, exhibitionism and/or voyeurism. IMPLICATIONS FOR PRACTICE: Samples of serial sexual homicide offenders will, fortunately, always be small, and it may be that more could be learned to assist in preventing such crimes if data from several studies or centres were pooled. Our findings suggest that an investigation of sexual homicide offenders should include strategies for evaluating premeditation as well as personality and paraphilic characteristics. Crime scene features that should alert investigators should include similar characteristics between victims and particular aspects of body exposure or organisation. PMID- 25111159 TI - Dynamic relationships between motor skill competence and health-related fitness in youth. AB - This cross-sectional study examined associations among motor skill competence (MSC) and health-related fitness (HRF) in youth. A convenient sample of 253 boys and 203 girls (aged 4-13 years) participated in the study. Associations among measures of MSC (throwing and kicking speed and standing long jump distance) and a composite measure of HRF (push-ups, curl-ups, grip strength and PACER test) across five age groups (4-5, 6-7, 8-9, 10-11 and 12-13 yrs.) were assessed using hierarchical regression modeling. When including all children, throwing and jumping were significantly associated with the composite HRF factor for both boys and girls (throw, t = 5.33; jump, t = 4.49) beyond the significant age effect (t = 4.98) with kicking approaching significance (t = 1.73, p = .08). Associations between throwing and kicking speed and HRF appeared to increase from early to middle to late childhood age ranges. Associations between jumping and HRF were variable across age groups. These results support the notion that the relationship between MSC and HRF performance are dynamic and may change across childhood. These data suggest that the development of object control skills in childhood may be important for the development and maintenance of HRF across childhood and into adolescence. PMID- 25111160 TI - Modified Chrispin-Norman score: correlation with peak exercise capacity and efficiency of ventilation in children with cystic fibrosis. AB - The modified Chrispin-Norman radiography score (CNS) is used in evaluation of radiographic changes in children with cystic fibrosis (CF). We evaluated the correlation of modified CNS with peak exercise capacity (Wpeak) and ventilatory efficiency (reflected by breathing reserve index-BRI) during progressive cardiopulmonary exercise testing (CPET). Thirty-six children aged 8-17 years were stratified according to their CNS into 3 groups: mild (<10), moderate (10-15), and severe (>15). CPET was performed on a cycle ergometer. Lung function tests included spirometry and whole-body plethysmography. Patients with higher CNS had lower FEV1 (p < .001), Wpeak predicted (%; p = .01) and lower mean peak oxygen consumption (VO2peak/kg; p = .014). The BRI at the anaerobic threshold and at Wpeak was elevated in patients with the highest CNS values (p < .001). The modified CNS correlates moderately with Wpeak (R = -0.443; p = .007) and BRI (R = -0.419; p = .011). Stepwise multiple linear regression showed that RV/TLC was the best predictor of Wpeak/pred (%; B = -0.165; ? = -0.494; R2 = .244; p = .002). Children with CF who have high modified CNS exhibit decreased exercise tolerance and ventilatory inefficacy during progressive effort. PMID- 25111161 TI - Running activity profile of adolescent tennis players during match play. AB - The aims of this study were (1) to assess the running activities of adolescent tennis players during match play with respect to velocity, acceleration, and deceleration; (2) to characterize changes in these activities during the course of a match; and (3) to identify potential differences between winners and losers. Twenty well-trained adolescent male athletes (13 +/- 1 y) played one simulated match each (giving a total of 10 matches), during which distances covered at different velocity categories (0 to < 1, 1 to < 2, 2 to < 3, 3 to < 4, and >= 4 m.s(-1)) and number of running activities involving high velocity (>= 3 m.s(-1)), acceleration (>= 2 m.s(-2)), and deceleration (<= -2 m.s(-2)) were monitored using a global positioning system (10 Hz). Heart rate was also assessed. The total match time, total distance covered, peak velocity, and mean heart rate were 81.2 +/- 14.6 min, 3362 +/- 869 m, 4.4 +/- 0.8 m.s(-1), and 159 +/- 12 beats.min( 1), respectively. Running activities involving high acceleration (0.6 +/- 0.2 n.min(-1)) or deceleration (0.6 +/- 0.2 n.min(-1)) were three times as frequent as those involving high velocity (0.2 +/- 0.1 n.min(-1)). No change in the pattern of running activities (P >= .13, d <= 0.39) and no differences between winners and losers (P >= .22, d <= 0.53) were evident during match play. We conclude that training of well-trained adolescent male tennis players need not focus on further development of their running abilities, since this physical component of multifactorial tennis performance does not change during the course of a match and does not differ between the winners and losers. PMID- 25111162 TI - From filter paper to porous carbon composite membrane oxygen reduction catalyst. AB - A novel type of porous carbon composite membrane (PCCM) based on the low-cost common filter paper via a simple route is reported. The obtained material exhibited excellent electrocatalytic activities toward the oxygen reduction reaction, high tolerance of methanol crossover, and durability in alkaline solution. PMID- 25111163 TI - Muscle activity and spine load during anterior chain whole body linkage exercises: the body saw, hanging leg raise and walkout from a push-up. AB - This study examined anterior chain whole body linkage exercises, namely the body saw, hanging leg raise and walkout from a push-up. Investigation of these exercises focused on which particular muscles were challenged and the magnitude of the resulting spine load. Fourteen males performed the exercises while muscle activity, external force and 3D body segment motion were recorded. A sophisticated and anatomically detailed 3D model used muscle activity and body segment kinematics to estimate muscle force, and thus sensitivity to each individual's choice of motor control for each task. Gradations of muscle activity and spine load characteristics were observed across tasks. On average, the hanging straight leg raise created approximately 3000 N of spine compression while the body saw created less than 2500 N. The hanging straight leg raise created the highest challenge to the abdominal wall (>130% MVC in rectus abdominis, 88% MVC in external oblique). The body saw resulted in almost 140% MVC activation of the serratus anterior. All other exercises produced substantial abdominal challenge, although the body saw did so in the most spine conserving way. These findings, along with consideration of an individual's injury history, training goals and current fitness level, should assist in exercise choice and programme design. PMID- 25111164 TI - Coxsackievirus can persist in murine pancreas by deletion of 5' terminal genomic sequences. AB - Enterovirus infections are generally acute and rapidly cleared by the host immune response. Enteroviruses can at times persist in immunologically intact individuals after the rise of the type-specific neutralizing immune response. The mechanism of enterovirus persistence was shown in group B coxsackieviruses (CVB) to be due to naturally-occurring deletions at the 5' terminus of the genome which variably impact the stem-loop secondary structure called domain I. These deletions result in much slower viral replication and a loss of measurable cytopathic effect when such 5' terminally deleted (TD) viruses are assayed in cell culture. The existence and persistence of CVB-TD long after the acute phase of infection has been documented in hearts of experimentally inoculated mice and naturally infected humans but to date, the existence of TD enteroviral populations have not been documented in any other organ. Enteroviral infections have been shown to impact type 1 diabetes (T1D) onset in humans as well as in the non-obese diabetic mouse model of T1D. The first step to studying the potential impact of CVB-TD on T1D etiology is to determine whether CVB-TD populations can arise in the pancreas. After inoculation of NOD diabetic mice with CVB, viral RNA persists in the absence of cytopathic virus in pancreas weeks past the acute infectious period. Analysis of viral genomic 5' termini by RT-PCR showed CVB-TD populations displace the parental population during persistent replication in murine pancreata. PMID- 25111165 TI - Hydrogen peroxide enhances the oxidation of oxygenated volatile organic compounds on mineral dust particles: a case study of methacrolein. AB - Heterogeneous oxidation of oxygenated volatile organic compounds (OVOCs) serves as an important sink of OVOCs as well as a source of secondary organic material. However, the roles of gas phase oxidants in these reactions are poorly understood. In this work, we present the first laboratory study of the heterogeneous reactions of methacrolein (MACR) on various mineral dust particles in the presence of gaseous H2O2. It is found that the presence of gaseous H2O2 significantly promotes both the uptake and oxidation of MACR on kaolinite, alpha Al2O3, alpha-Fe2O3, and TiO2, but not on CaCO3. The oxidation of MACR produces organic acids as its major low-molecular-weight product, whose yields are enhanced by a factor of 2-6 in the presence of H2O2. In addition, organic peroxides such as methyl hydroperoxide, peroxyformic acid, and peroxyacetic acid are only formed in the presence of H2O2, and the formation of methyl hydroperoxide indicates that MACR oxidation on the surface involves reaction with OH radicals. A probe reaction using salicylic acid verifies the production of OH radicals from H2O2 decomposition on kaolinite, alpha-Al2O3, alpha-Fe2O3, and TiO2, which rationalizes the enhanced MACR oxidation observed on these particles. The uptake coefficients of MACR on kaolinite, alpha-Fe2O3, and TiO2 in the presence of H2O2 are on the order of 10(-5)-10(-4). Our results provide new insights into the formation and chemical evolution of organic species in the atmosphere. PMID- 25111167 TI - Impact of an adherence program to antiretroviral treatment on virologic response in a cohort of multitreated and poorly adherent HIV-infected patients in Spain. AB - Several studies have shown the importance of adherence to highly active antiretroviral therapy (HAART) in achieving HIV-1 suppression. However, most have focused on naive patients and do not assess the impact of HAART on viral load (VL). Our aim was to evaluate the effectiveness of an adherence program in a cohort of multitreated and poorly adherent patients. We performed a cohort study of all adult HIV-1 infected patients with detectable VL who were treatment experienced and poorly adherent to HAART, included in an adherence program since its introduction in 2009 (n=136). The adherence program consisted of a multidisciplinary team with a nurse who specialized in behavioral intervention, counselling on substance abuse, and motivational interviewing, as well as a social worker responsible for referring patients to local healthcare centers. Effectiveness was evaluated as percentage of patients with VL <50 copies/mL at week 48 by modified intent-to-treat (mITT) analysis. Initially, 76.6% of the patients had an adherence <30% according to the Simplified Medication Adherence Questionnaire (SMAQ). At 48 weeks, 48.1% of the patients had VL <50 copies/mL, and the adherence was >90% in 71% of the patients. In multivariate analysis, a ratio of bottle refill per month >0.9 during the study [odds ratio (OR) 14.3; 95% confidence interval (CI) 4.08-50.08, p<0.001] and being on a b.i.d. regimen (OR 12.5; 95% CI 1.81-86.4, p=0.010) were associated with an undetectable VL. In conclusion, the adherence program was successful in almost half of the patients, despite their long treatment experience and prior poor adherence. This strategy may help to prevent disease progression and the risk of HIV transmission in these patients. PMID- 25111168 TI - Field effectiveness of hepatitis A vaccine and uptake of post exposure prophylaxis following a change to the Australian guidelines. AB - BACKGROUND: In 2009, national guidelines for hepatitis A control in Australia changed to recommend hepatitis A vaccine (HAV), instead of normal human immune globulin (NHIG), for post-exposure prophylaxis (PEP). AIMS: (1) Determine whether the uptake of PEP among contacts of hepatitis A cases changed after the introduction of the new guidelines, and (2) assess the field effectiveness of the HAV used as PEP in preventing infection among contacts of hepatitis A cases. METHODS: A retrospective cohort of contacts from hepatitis A cases reported to metropolitan Public Health Units in Sydney, Australia, between October 2008 and June 2010, was identified. Contacts were analysed by time period, age, PEP type, and susceptibility to hepatitis A. The relative risk (RR) of hepatitis A infection among susceptible contacts who received HAV, compared with susceptible contacts who had not received HAV, was calculated to estimate the effectiveness of the HAV when used as PEP. RESULTS: The uptake of PEP by susceptible contacts increased from 76% (n=133) to 89% (n=127) after the introduction of the new guidelines. Before the change in guidelines, no one who received PEP was later reported with hepatitis A. After the change in guidelines, one of the 123 contacts who received HAV as PEP was subsequently reported with hepatitis A. However, this case was likely to have been co-exposed with a primary case. Conservatively, assuming this was a secondary case, the vaccine effectiveness of HAV was 95.6% (66.1%-99.4%). Nine of 10 incident cases of hepatitis A were contacts who did not receive any PEP. CONCLUSION: The improved uptake of PEP and the high estimate of the effectiveness of HAV provides support for using HAV for PEP. The very high occurrence of hepatitis A among contacts who did not receive any PEP further highlights the importance of PEP in preventing hepatitis A infection. PMID- 25111166 TI - Effects of the absence of apolipoprotein e on lipoproteins, neurocognitive function, and retinal function. AB - IMPORTANCE: The identification of a patient with a rare form of severe dysbetalipoproteinemia allowed the study of the consequences of total absence of apolipoprotein E (apoE). OBJECTIVES: To discover the molecular basis of this rare disorder and to determine the effects of complete absence of apoE on neurocognitive and visual function and on lipoprotein metabolism. DESIGN, SETTING, AND PARTICIPANTS: Whole-exome sequencing was performed on the patient's DNA. He underwent detailed neurological and visual function testing and lipoprotein analysis. Lipoprotein analysis was also performed in the Cardiovascular Research Institute, University of California, San Francisco, on blood samples from the proband's mother, wife, 2 daughters, and normolipidemic control participants. MAIN OUTCOME MEASURES: Whole-exome sequencing, lipoprotein analysis, and neurocognitive function. RESULTS: The patient was homozygous for an ablative APOE frameshift mutation (c.291del, p.E97fs). No other mutations likely to contribute to the phenotype were discovered, with the possible exception of two, in ABCC2 (p.I670T) and LIPC (p.G137R). Despite complete absence of apoE, he had normal vision, exhibited normal cognitive, neurological, and retinal function, had normal findings on brain magnetic resonance imaging, and had normal cerebrospinal fluid levels of beta-amyloid and tau proteins. He had no significant symptoms of cardiovascular disease except a suggestion of myocardial ischemia on treadmill testing and mild atherosclerosis noted on carotid ultrasonography. He had exceptionally high cholesterol content (760 mg/dL; to convert to millimoles per liter, multiply by 0.0259) and a high cholesterol to triglycerides ratio (1.52) in very low-density lipoproteins with elevated levels of small-diameter high-density lipoproteins, including high levels of prebeta-1 high-density lipoprotein. Intermediate-density lipoproteins, low-density lipoproteins, and very low-density lipoproteins contained elevated apoA-I and apoA-IV levels. The patient's apoC-III and apoC-IV levels were decreased in very low-density lipoproteins. Electron microscopy revealed large lamellar particles having electron-opaque cores attached to electron-lucent zones in intermediate density and low-density lipoproteins. Low-density lipoprotein particle diameters were distributed bimodally. CONCLUSIONS AND RELEVANCE: Despite a profound effect on lipoprotein metabolism, detailed neurocognitive and retinal studies failed to demonstrate any defects. This suggests that functions of apoE in the brain and eye are not essential or that redundant mechanisms exist whereby its role can be fulfilled. Targeted knockdown of apoE in the central nervous system might be a therapeutic modality in neurodegenerative disorders. PMID- 25111170 TI - Highly drug-resistant pathogens implicated in burn-associated bacteremia in an Iraqi burn care unit. AB - OBJECTIVE: In low- and middle-income countries, bloodstream infections are an important cause of mortality in patients with burns. Increasingly implicated in burn-associated infections are highly drug-resistant pathogens with limited treatment options. We describe the epidemiology of bloodstream infections in patients with burns in a humanitarian surgery project in Iraq. METHODS: We performed a retrospective, descriptive study of blood culture isolates identified between July 2008 and September 2009 among patients with burns in a single hospital in Iraq who developed sepsis. RESULTS: In 1169 inpatients admitted to the burn unit during the study period, 212 (18%) had suspected sepsis, and 65 (6%) had confirmed bacteremia. Sepsis was considered the primary cause of death in 198 patients (65%; 95% CI 65-70) of the 304 patients that died. The most commonly isolated organisms were Pseudomonas aeruginosa (22 isolates [34%]), Staphylococcus aureus (17 [26%]), Klebsiella pneumoniae (8 [12%]), Staphylococcus epidermidis (7 [11%]), Acinetobacter baumannii (6 [9%]), and Enterobacter cloacae (5 [8%]). A high proportion of Enterobacteriaceae strains produced extended spectrum beta-lactamase and S. aureus isolates were uniformly methicillin resistant. For gram-negative bacteria, the most reliably active antibiotics were imipenen and amikacin. CONCLUSIONS: Burn patients with sepsis in Iraq were commonly found to have bloodstream pathogens resistant to most antibiotics available locally. Effective empirical therapy of burn sepsis in this region of Iraq would consist of vancomycin or teicoplanin and a carbapenem-class antibiotic with antipseudomonal activity. PMID- 25111172 TI - Long-term outcome in PSC/AIH "overlap syndrome": does immunosuppression also treat the PSC component? PMID- 25111169 TI - Adjuvants for vaccines to drugs of abuse and addiction. AB - Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA. PMID- 25111171 TI - Changing indications and socio-demographic determinants of (adeno)tonsillectomy among children in England--are they linked? A retrospective analysis of hospital data. AB - OBJECTIVE: To assess whether increased awareness and diagnosis of obstructive sleep apnoea syndrome (OSAS) and national guidance on tonsillectomy for recurrent tonsillitis have influenced the socio-demographic profile of children who underwent tonsillectomy over the last decade. METHOD: Retrospective time-trends study of Hospital Episodes Statistics data. We examined the age, sex and deprivation level, alongside OSAS diagnoses, among children aged <16 years who underwent (adeno)tonsillectomy in England between 2001/2 and 2011/12. RESULTS: Among children aged <16 years, there were 29,697 and 27,732 (adeno)tonsillectomies performed in 2001/2 and 2011/12, respectively. The median age at (adeno)tonsillectomy decreased from 7 (IQR: 5-11) to 5 (IQR: 4-9) years over the decade. (Adeno)tonsillectomy rates among children aged 4-15 years decreased by 14% from 350 (95%CI: 346-354) in 2001/2 to 300 (95%CI: 296-303) per 100,000 children in 2011/12. However, (adeno)tonsillectomy rates among children aged <4 years increased by 58% from 135 (95%CI: 131-140) to 213 (95%CI 208-219) per 100,000 children in 2001/2 and 2011/2, respectively. OSAS diagnoses among children aged <4 years who underwent surgery increased from 18% to 39% between these study years and the proportion of children aged <4 years with OSAS from the most deprived areas increased from 5% to 12%, respectively. CONCLUSIONS: (Adeno)tonsillectomy rates declined among children aged 4-15 years, which reflects national guidelines recommending the restriction of the operation to children with more severe recurrent throat infections. However, (adeno)tonsillectomy rates among pre-school children substantially increased over the past decade and one in five children undergoing the operation was aged <4 years in 2011/12.The increase in surgery rates in younger children is likely to have been driven by increased awareness and detection of OSAS, particularly among children from the most deprived areas. PMID- 25111173 TI - Monitoring dominant strictures in primary sclerosing cholangitis with brush cytology and FDG-PET. AB - BACKGROUND & AIMS: Despite a high risk of cholangiocellular adenocarcinoma (CCA) it is unclear how surveillance of patients with primary sclerosing cholangitis (PSC) should be performed. METHODS: We evaluated a follow-up algorithm of brush cytology and positron emission tomography/computed tomography with [(18)F] fluorodeoxyglucose ([(18)F]FDG-PET/CT), measured as maximum standardized uptake values, normalized to the liver background (SUVmax/liver) at 180 min, in PSC patients with dominant bile duct strictures. RESULTS: Brush cytology with high grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding a diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 56%, 89%, 75%, and 88%, respectively. Preemptive liver transplantations due to repeated HGD before manifest CCA were performed in six patients. Receiver operating characteristic (ROC) analysis of [(18)F]FDG uptake showed that a SUVmax/liver quotient of 3.3 was able to discriminate between CCA and non-malignant disease with a sensitivity, specificity, PPV and NPV for CCA of 89%, 92%, 62%, 98%, respectively. A SUVmax/liver >3.3 detected CCA in 8/9 patients whereas a quotient <2.4 excluded CCA. Combining brush cytology and quantitative [(18)F]FDG-PET/CT yielded a sensitivity for HGD and/or CCA of 100% and a specificity of 88%. CONCLUSION: Early detection of HGD before manifest CCA is feasible with repeated brush cytology and may allow for preemptive liver transplantation. [(18)F]FDG-PET/CT has a high sensitivity for manifest CCA and a negative scan indicates a non-malignant state of the disease. Brush cytology and [(18)F]FDG-PET/CT are complementary in monitoring and managing PSC patients with dominant strictures. PMID- 25111175 TI - The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning. AB - BACKGROUND & AIMS: Most liver grafts undergoing transplantation derive from brain dead donors, which may also show hepatic steatosis, being both characteristic risk factors in liver transplantation. Ischemic preconditioning shows benefits when applied in non-brain dead clinical situations like hepatectomies, whereas it has been less promising in the transplantation from brain dead patients. This study examined how brain death affects preconditioned steatotic and non-steatotic liver grafts undergoing transplantation. METHODS: Steatotic and non-steatotic grafts from non-brain dead and brain dead-donors were cold stored for 6h and then transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed. In addition, two therapeutic strategies, ischemic preconditioning and/or acetylcholine pre-treatment, and their underlying mechanisms were characterized. RESULTS: Preconditioning benefits in non-brain dead donors were associated with nitric oxide and acetylcholine generation. In brain dead donors, preconditioning generated nitric oxide but did not promote acetylcholine upregulation, and this resulted in inflammation and damage. Acetylcholine treatment in brain dead donors, through PKC, increased antioxidants and reduced lipid peroxidation, nitrotyrosines and neutrophil accumulation, altogether protecting against damage. The combination of acetylcholine and preconditioning conferred stronger protection against damage, oxidative stress and neutrophil accumulation than acetylcholine treatment alone. These superior beneficial effects were due to a selective preconditioning-mediated generation of nitric oxide and regulation of PPAR and TLR4 pathways, which were not observed when acetylcholine was administered alone. CONCLUSIONS: Our findings propose the combination of acetylcholine+preconditioning as a feasible and highly protective strategy to reduce the adverse effects of brain death and to ultimately improve liver graft quality. PMID- 25111174 TI - Correction of hyponatraemia improves cognition, quality of life, and brain oedema in cirrhosis. AB - BACKGROUND & AIMS: Hyponatraemia in cirrhosis is associated with impaired cognition and poor health-related quality of life (HRQOL). However, the benefit of hyponatraemia correction is unclear. The aim of this study was to evaluate the effect of tolvaptan on serum sodium (Na), cognition, HRQOL, companion burden, and brain MRI (volumetrics, spectroscopy, and diffusion tensor imaging) in cirrhotics with hyponatraemia. METHODS: Cirrhotics with Na <130 mEq/L were included for a four-week trial. At screening, patients underwent cognitive and HRQOL testing, serum/urine chemistries and companion burden assessment. Patients then underwent fluid restriction and diuretic withdrawal for two weeks after which cognitive tests were repeated. If Na was still <130 mEq/L, brain magnetic resonance imaging (MRI) was performed and tolvaptan was initiated for 14 days with frequent clinical/laboratory monitoring. After 14 days of tolvaptan, all tests were repeated. Comparisons were made between screen, pre-and post-drug periods Na, urine/serum laboratories, cognition, HRQOL and companion burden. RESULTS: 24 cirrhotics were enrolled; seven normalized Na without tolvaptan with improvement in cognition. The remaining 17 received tolvaptan of which 14 completed the study over 13 +/- 2 days (age 58 +/- 6 years, MELD 17, 55% HCV, median 26 mg/day of tolvaptan). Serum Na and urine free water clearance increased with tolvaptan without changes in mental status or liver function. Cognitive function, HRQOL and companion burden only improved in these 14 patients after tolvaptan, along with reduced total brain and white matter volume, increase in choline on magnetic resonance spectroscopy, and reduced cytotoxic oedema. CONCLUSIONS: Short-term tolvaptan therapy is well tolerated in cirrhosis. Hyponatraemia correction is associated with cognitive, HRQOL, brain MRI and companion burden improvement. PMID- 25111177 TI - Genetic predisposition to hepatocellular carcinoma in alcoholic cirrhosis: the NCAN-PNPLA3-lipid connection? PMID- 25111176 TI - S100A4 promotes liver fibrosis via activation of hepatic stellate cells. AB - BACKGROUND & AIMS: S100A4 has been linked to the fibrosis of several organs due to its role as a fibroblast-specific marker. However, the role of S100A4 itself in the development of fibrosis has not been much investigated. Here, we determined whether S100A4 regulates liver fibrogenesis and examined its mechanism by focusing on the activation of hepatic stellate cells (HSCs). METHODS: S100A4 deficient mice were used to determine the role of S100A4 in liver fibrogenesis. The effect of S100A4 on HSC activation was estimated by using primary mouse HSCs and the human HSC cell line LX-2. Serum levels of S100A4 in cirrhotic patients were determined by ELISA. RESULTS: S100A4 was found to be secreted by a subpopulation of macrophages and to promote the development of liver fibrosis. It accumulated in the liver during the progression of liver fibrosis and activated HSCs in mice. In vitro studies demonstrated that S100A4 induced the overexpression of alpha-smooth muscle actin through c-Myb in HSCs. Both, the selective depletion of S100A4-expressing cells and knockdown of S100A4 in the liver by RNA interference, resulted in a reduction of liver fibrosis following injury. Importantly, increased S100A4 levels in both the liver tissue and serum correlated positively with liver fibrosis in humans. CONCLUSIONS: S100A4 promotes liver fibrosis by activating HSCs, which may represent a potential target for anti-fibrotic therapies. PMID- 25111178 TI - A high throughput screen identifies potent and selective inhibitors to human epithelial 15-lipoxygenase-2. AB - Lipoxygenase (LOX) enzymes catalyze the hydroperoxidation of arachidonic acid and other polyunsaturated fatty acids to hydroxyeicosatetraenoic acids with varying positional specificity to yield important biological signaling molecules. Human epithelial 15-lipoxygenase-2 (15-LOX-2) is a highly specific LOX isozyme that is expressed in epithelial tissue and whose activity has been correlated with suppression of tumor growth in prostate and other epithelial derived cancers. Despite the potential utility of an inhibitor to probe the specific role of 15 LOX-2 in tumor progression, no such potent/specific 15-LOX-2 inhibitors have been reported to date. This study employs high throughput screening to identify two novel, specific 15-LOX-2 inhibitors. MLS000545091 is a mixed-type inhibitor of 15 LOX-2 with a Ki of 0.9+/-0.4 uM and has a 20-fold selectivity over 5-LOX, 12-LOX, 15-LOX-1, COX-1, and COX-2. MLS000536924 is a competitive inhibitor with a Ki of 2.5+/-0.5 uM and also possesses 20-fold selectivity toward 15-LOX-2 over the other oxygenases, listed above. Finally, neither compound possesses reductive activity towards the active-site ferrous ion. PMID- 25111179 TI - Characterization of nodal/TGF-lefty signaling pathway gene variants for possible roles in congenital heart diseases. AB - BACKGROUND: Nodal/TGF-Lefty signaling pathway has important effects at early stages of differentiation of human embryonic stem cells in directing them to differentiate into different embryonic lineages. LEFTY, one of transforming growth factors in the Nodal/TGF-Lefty signaling pathway, plays an important role in the development of heart. The aim of this work was to find evidence on whether Lefty variations are associated with congenital heart diseases (CHD). METHODS: We sequenced the Lefty gene for 230 Chinese Han CHD patients and evaluated SNPs rs2295418, rs360057 and g.G169A, which are located within the translated regions of the genes. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using online software OEGE, and multiple-sequence alignments of LEFTY proteins were carried out using the Vector NTI software. RESULTS: Two heterozygous variants in Lefty1 gene, g.G169A and g.A1035C, and one heterozygous variant in Lefty2 gene, g.C925A, were identified. Statistical analyses showed that the rs2295418 (g.C925A) variant in Lefty2 gene was obviously associated with the risk of CHD (P value = 0.016<0.05). The genotype frequency of rs360057 (g.A1035C) variant in Lefty1 gene was associated with the risk of CHD (P value = 0.007<0.05), but the allele frequency was not (P value = 0.317>0.05). CONCLUSIONS: The SNP rs2295418 in the Lefty2 gene is associated with CHD in Chinese Han populations. PMID- 25111181 TI - Ecofriendly porphyrin synthesis by using water under microwave irradiation. AB - Water, under microwave irradiation and at a temperature of 473 K, reaches pressures above 16 bar, being capable to act as catalyst, without the use of organic solvents and oxidants, for meso-substituted porphyrin synthesis. Sustainability of the reaction is proved by E Factor=35 and EcoScale value of 50.5, the highest so far obtained for porphyrin synthesis. Methodology's wide versatility is clearly demonstrated by the good yields obtained for both aryl and alkyl substituted porphyrins. These reaction conditions represent a huge development, not only by using very high concentrations, minimizing organic solvent usage, but also by eradicating toxic expensive solvents and oxidants. PMID- 25111180 TI - A splicing mutation in the novel mitochondrial protein DNAJC11 causes motor neuron pathology associated with cristae disorganization, and lymphoid abnormalities in mice. AB - Mitochondrial structure and function is emerging as a major contributor to neuromuscular disease, highlighting the need for the complete elucidation of the underlying molecular and pathophysiological mechanisms. Following a forward genetics approach with N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis, we identified a novel mouse model of autosomal recessive neuromuscular disease caused by a splice-site hypomorphic mutation in a novel gene of unknown function, DnaJC11. Recent findings have demonstrated that DNAJC11 protein co immunoprecipitates with proteins of the mitochondrial contact site (MICOS) complex involved in the formation of mitochondrial cristae and cristae junctions. Homozygous mutant mice developed locomotion defects, muscle weakness, spasticity, limb tremor, leucopenia, thymic and splenic hypoplasia, general wasting and early lethality. Neuropathological analysis showed severe vacuolation of the motor neurons in the spinal cord, originating from dilatations of the endoplasmic reticulum and notably from mitochondria that had lost their proper inner membrane organization. The causal role of the identified mutation in DnaJC11 was verified in rescue experiments by overexpressing the human ortholog. The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane whereas putative additional isoforms displayed differential submitochondrial localization. Moreover, we showed that DNAJC11 is assembled in a high molecular weight complex, similarly to mitofilin and that downregulation of mitofilin or SAM50 affected the levels of DNAJC11 in HeLa cells. Our findings provide the first mouse mutant for a putative MICOS protein and establish a link between DNAJC11 and neuromuscular diseases. PMID- 25111182 TI - SpyAvidin hubs enable precise and ultrastable orthogonal nanoassembly. AB - The capture of biotin by streptavidin is an inspiration for supramolecular chemistry and a central tool for biological chemistry and nanotechnology, because of the rapid and exceptionally stable interaction. However, there is no robust orthogonal interaction to this hub, limiting the size and complexity of molecular assemblies that can be created. Here we combined traptavidin (a streptavidin variant maximizing biotin binding strength) with an orthogonal irreversible interaction. SpyTag is a peptide engineered to form a spontaneous isopeptide bond to its protein partner SpyCatcher. SpyTag or SpyCatcher was successfully fused to the C-terminus of Dead streptavidin subunits. We were able to generate chimeric tetramers with n (0 <= n <= 4) biotin binding sites and 4-n SpyTag or SpyCatcher binding sites. Chimeric SpyAvidin tetramers bound precise numbers of ligands fused to biotin or SpyTag/SpyCatcher. Mixing chimeric tetramers enabled assembly of SpyAvidin octamers (8 subunits) or eicosamers (20 subunits). We validated assemblies using electrophoresis and native mass spectrometry. Eicosameric SpyAvidin was used to cluster trimeric major histocompatibility complex (MHC) class I:beta2-microglobulin:peptide complexes, generating an assembly with up to 56 components. MHC eicosamers surpassed the conventional MHC tetramers in acting as a powerful stimulus to T cell signaling. Combining ultrastable noncovalent with irreversible covalent interaction, SpyAvidins enable a simple route to create robust nanoarchitectures. PMID- 25111183 TI - Different gDNA content in the subpopulations of prostate cancer extracellular vesicles: apoptotic bodies, microvesicles, and exosomes. AB - BACKGROUND: Extracellular vesicles (EVs) are cell-derived membrane vesicles. EVs contain several RNAs such as mRNA, microRNAs, and ncRNAs, but less is known of their genomic DNA (gDNA) content. It is also unknown whether the DNA cargo is randomly sorted or if it is systematically packed into specific EV subpopulations. The aim of this study was to analyze whether different prostate cancer (PCa) cell-derived EV subpopulations (apoptotic bodies, microvesicles, and exosomes) carry different gDNA fragments. METHODS: EV subpopulations were isolated from three PCa cell lines (LNCaP, PC-3, and RC92a/hTERT) and the plasma of PCa patients and healthy donors, and characterized by transmission electron microscopy, nanoparticle tracking analysis and total protein content. gDNA fragments of different genes were detected by real time quantitative PCR and confirmed by DNA sequencing. RESULTS: We report that the concentration of EVs was higher in the cancer patients than in the healthy controls. EV subpopulations differed from each other in terms of total protein and DNA content. Analysis of gDNA fragments of MLH1, PTEN, and TP53 genes from the PCa cell-derived EV subpopulations showed that different EVs carried different gDNA content, which could even harbor specific mutations. Altogether, these results suggest that both nucleic acids and proteins are selectively and cell-dependently packed into the EV subtypes. CONCLUSIONS: EVs derived from PCa cell lines and human plasma samples contain double-stranded gDNA fragments which could be used to detect specific mutations, making EVs potential biomarkers for cancer diagnostics and prognostics. PMID- 25111184 TI - The effect of processing on the surface physical stability of amorphous solid dispersions. AB - The focus of this study was to investigate the effect of processing on the surface crystallization of amorphous molecular dispersions and gain insight into the mechanisms underpinning this effect. The model systems, amorphous molecular dispersions of felodipine-EUDRAGIT(r) E PO, were processed both using spin coating (an ultra-fast solvent evaporation based method) and hot melt extrusion (HME) (a melting based method). Amorphous solid dispersions with drug loadings of 10-90% (w/w) were obtained by both processing methods. Samples were stored under 75% RH/room temperatures for up to 10months. Surface crystallization was observed shortly after preparation for the HME samples with high drug loadings (50-90%). Surface crystallization was characterized by powder X-ray diffraction (PXRD), ATR FTIR spectroscopy and imaging techniques (SEM, AFM and localized thermal analysis). Spin coated molecular dispersions showed significantly higher surface physical stability than hot melt extruded samples. For both systems, the progress of the surface crystal growth followed zero order kinetics on aging. Drug enrichment at the surfaces of HME samples on aging was observed, which may contribute to surface crystallization of amorphous molecular dispersions. In conclusion it was found the amorphous molecular dispersions prepared by spin coating had a significantly higher surface physical stability than the corresponding HME samples, which may be attributed to the increased process related apparent drug-polymer solubility and reduced molecular mobility due to the quenching effect caused by the rapid solvent evaporation in spin coating. PMID- 25111186 TI - Interactive effects of contextual cues and acute alcohol intoxication on the associations between alcohol expectancy activation and urge to drink. AB - This study examined the joint effects of contextual cues and alcohol intoxication on the associations between activation of positive and negative alcohol expectancies in memory and self-reported urges to drink alcohol after a laboratory alcohol administration. Young adult heavy drinkers were randomly assigned to drink a moderate dose of alcohol or a placebo (alcohol manipulation), and then listened to positive or negative drinking scenarios (cue manipulation). Before and after these manipulations, participants completed an alcohol expectancy Stroop task assessing positive and negative expectancy activation, as well as self-report measures of urges to drink. Regression analyses revealed that the alcohol and cue manipulations had a joint, moderating impact on the associations between expectancy activation and postcue changes in urge to drink. Specifically, both increased activation of negative expectancies and decreased activation of positive expectancies predicted decreases in urges to drink, but only for intoxicated participants in the negative cue condition. There were no associations between expectancy activation and urges to drink for those in the positive cue condition regardless of beverage condition. Results suggest that whether memory activation of alcohol expectancies has an impact on urge to drink after alcohol is on board may depend on the relevance of the activated expectancies to the current drinking context. This process appears to be influenced by a complex interaction between contextual cues in the environment and the pharmacological effects of alcohol. PMID- 25111185 TI - Dendritic cell-mediated, DNA-based vaccination against hepatitis C induces the multi-epitope-specific response of humanized, HLA transgenic mice. AB - Hepatitis C virus (HCV) is the etiologic agent of chronic liver disease, hepatitis C. Spontaneous resolution of viral infection is associated with vigorous HLA class I- and class II-restricted T cell responses to multiple viral epitopes. Unfortunately, only 20% of patients clear infection spontaneously, most develop chronic disease and require therapy. The response to chemotherapy varies, however; therapeutic vaccination offers an additional treatment strategy. To date, therapeutic vaccines have demonstrated only limited success. Vector mediated vaccination with multi-epitope-expressing DNA constructs alone or in combination with chemotherapy offers an additional treatment approach. Gene sequences encoding validated HLA-A2- and HLA-DRB1-restricted epitopes were synthesized and cloned into an expression vector. Dendritic cells (DCs) derived from humanized, HLA-A2/DRB1 transgenic (donor) mice were transfected with these multi-epitope-expressing DNA constructs. Recipient HLA-A2/DRB1 mice were vaccinated s.c. with transfected DCs; control mice received non-transfected DCs. Peptide-specific IFN-gamma production by splenic T cells obtained at 5 weeks post immunization was quantified by ELISpot assay; additionally, the production of IL 4, IL-10 and TNF-alpha were quantified by cytokine bead array. Splenocytes derived from vaccinated HLA-A2/DRB1 transgenic mice exhibited peptide-specific cytokine production to the vast majority of the vaccine-encoded HLA class I- and class II-restricted T cell epitopes. A multi-epitope-based HCV vaccine that targets DCs offers an effective approach to inducing a broad immune response and viral clearance in chronic, HCV-infected patients. PMID- 25111187 TI - Sheet-type titania, but not P25, induced paraptosis accompanying apoptosis in murine alveolar macrophage cells. AB - In this study, we identified the toxic effects of sheet-type titania (TNS), which are being developed as a material for UV-blocking glass, comparing with P25, a benchmark control for titania, in MH-S cells, a mouse alveolar macrophage cell line. After 24 h exposure, the TNS-exposed cells formed large vacuoles while the P25-exposed ones did not. The decreased levels of cell viability were similar between the P25 and TNS groups, but ATP production was clearly lower in cells exposed to the TNS. P25 decreased the expression of calnexin protein, an endoplasmic reticulum (ER) membrane marker, and increased the number of cells generating ROS in a dose dependent manner. Meanwhile, TNS dilated the ER and mitochondria and increased the secretion of NO and pro-inflammatory cytokines, but not of ROS. Subsequently, we studied the molecular response following TNS induced vacuolization. TNS started to form vacuoles in the cytosol since 20 min after exposure, and the expression of the mitochondria function-related genes were down-regulated the most in the cells exposed for 1 h. After 24 h exposure, the number of apoptotic cells and the relative levels of BAX to Bcl-2 increased. The expression of SOD1 protein, but not of SOD2, also dose-dependently increased with an increase in caspase-8 activity. Additionally, the MAPK pathway was significantly activated, even though the expression of p-EGFR did not change significantly. Furthermore, the number of apoptotic cells increased rapidly with time and with the inhibition of vacuole formation. Taken together, we suggest that P25 and TNS may target different organelles. In addition, TNS, but not P25, induced paraptosis accompanied by apoptosis in MH-S cells, and the formation of the cytoplasmic vacuoles allowed delay apoptosis following TNS exposure. PMID- 25111188 TI - Development of an in vitro cytochrome P450 cocktail inhibition assay for assessing the inhibition risk of drugs of abuse. AB - Drugs of abuse are not tested for cytochrome P450 (CYP) inhibition potential before distribution. Therefore, a cocktail assay should be developed for testing the inhibition potential for all relevant CYPs. The following CYP test substrates and selective inhibitors were incubated in pooled human liver microsomes: phenacetin (alpha-naphthoflavone for CYP1A2), coumarin (tranylcypromine, CYP2A6), bupropion (sertraline, CYP2B6), amodiaquine (trimethoprim, CYP2C8), diclofenac (sulfaphenazole, CYP2C9), omeprazole (fluconazole, CYP2C19), dextromethorphan (quinidine, CYP2D6), chlorzoxazone (clomethiazole, CYP2E1), testosterone (verapamil, CYP3A). Samples were analyzed after protein precipitation using a Thermo Fisher Q-Exactive LC-high-resolution-MS/MS. The IC50 values were calculated by plotting the concentration of the formed metabolite, relative to the control sample, over the logarithm of the inhibitor concentration. They were determined either for single substrate or the cocktail incubation. Unfortunately, the cocktail assay had to be split because of interferences during incubation caused by substrates or metabolites, but the mixture of both incubates could be analyzed in one analytical run. The IC50 values determined in the single substrate or both cocktail incubations were comparable among themselves and with published data. In conclusion, the new inhibition cocktail assay was reproducible and applicable for testing the inhibition potential of drugs of abuse as exemplified for 2,5-dimethoxy-4-iodo-amfetamine (DOI). PMID- 25111189 TI - Case studies of hydrogen sulphide occupational exposure incidents in the UK. AB - The UK Health and Safety Executive has investigated several incidents of workplace accidents involving hydrogen sulphide exposure in recent years. Biological monitoring has been used in some incidents to determine the cause of unconsciousness resulting from these incidents and as a supporting evidence in regulatory enforcement. This paper reports on three case incidents and discusses the use of biological monitoring in such cases. Biological monitoring has a role in identifying hydrogen sulphide exposure in incidents, whether these are occupational or in the wider environment. Sample type, time of collection and sample storage are important factors in the applicability of this technique. For non-fatal incidents, multiple urine samples are recommended at two or more time points between the incident and 15 h post-exposure. For routine occupational monitoring, post-shift samples should be adequate. Due to endogenous levels of urinary thiosulphate, it is likely that exposures in excess of 12 ppm for 30 min (or 360 ppm/min equivalent) would be detectable using biological monitoring. This is within the Acute Exposure Guideline Level 2 (the level of the chemical in air at or above which there may be irreversible or other serious long-lasting effects or impaired ability to escape) for hydrogen sulphide. PMID- 25111190 TI - COMP does not directly modify the expression of genes involved in cartilage homeostasis in contrast to several other cartilage matrix proteins. AB - OBJECTIVE: We investigated whether COMP may modify cartilage metabolism and play a role as an endogenous disease aggravating factor in OA. MATERIALS AND METHODS: Full-length and momomeric COMP was recombinantly expressed in human embryonic kidney cells and purified it via affinity chromatography. Purified COMP was used to stimulate either primary human chondrocytes or cartilage explants. Changes in the expression profiles of inflammatory genes, differentiation markers and growth factors were examined by immunoassay and by quantitative real-time reverse transcription polymerase chain reaction. RESULTS: Incubation of primary human chondrocytes or cartilage explants in the presence of COMP did not induce statistically significant changes in the expression of IL-6, MMP1, MMP13, collagen I, collagen II, collagen X, TGF-beta1 and BMP-2. CONCLUSIONS: In contrast to collagen II and matrilin-3, COMP lacks the ability to trigger a proinflammatory response in chondrocytes, although it carries an RGD motif and can bind to integrins. COMP is a well-accepted biomarker for osteoarthritis but increased COMP levels do not necessarily correlate with inflammation. PMID- 25111191 TI - Comparison of equine articular cartilage thickness in various joints. AB - PURPOSE: Thicknesses of fresh equine articular cartilage surfaces from the fetlock, carpal and stifle joints were measured employing a needle probe test. MATERIALS AND METHODS: Eighty-seven samples used in measurement were cultivated from fetlock, carpal and stifle joints of 12 deceased within 4 h of death. After approximately three minutes of exposure to air during dissection, all cartilage samples were preserved in a saline solution to keep the articular cartilage hydrated for testing. The thickness was measured on five different spots on the same sample. The thicknesses of the fetlock, carpus and stifle were compared. RESULTS: The articular cartilage of the stifle was thicker than the fetlock and carpus, while the fetlock and the carpus had similar thickness values. The average thickness of the fetlock, carpal and stifle joint are 0.86, 0.87 and 2.1 mm, respectively. They were statistically compared using the Student t-test. The differences on the articular cartilage thicknesses between the fetlock and stifle, and carpus and stifle were "very highly significant" (p < 0.001). This indicates that the articular cartilage thickness of the stifle is significantly different from that of the fetlock and carpus. Four different surfaces in the fetlock and four in the carpal joint were also compared. Significant differences between each set of the four surfaces were not observed. In the carpus, the difference in thickness between the distal radius and proximal third carpal bone articular cartilage surfaces as well as the proximal radial carpal bone and distal radial carpal bone articular cartilage surfaces were statistically significant. PMID- 25111192 TI - Effect of S-methylisothiourea, an inducible nitric oxide synthase inhibitor, in joint pain and pathology in surgically induced model of osteoarthritis. AB - The aim of the present study was to evaluate in vivo modulatory effect of S methylisothiourea (SMT), a preferential inhibitor of inducible nitric oxide synthase (iNOS) on pain and pathology in the surgical model of osteoarthritis (OA) in rats. The OA was produced by the anterior cruciate ligament transection (ACLT) and medial meniscectomy (MMx) of right knee. SMT was administered 1 day prior to the production of OA and continued up to day 42 postoperation. Mechanical hyperalgesia, thermal hyperalgesia, tail flick latency after repeated flexion and extension of OA knee and knee diameter of right knee were determined at weekly intervals. Serum levels of IL-1beta, TNF-alpha and nitrite concentration were determined at the end of the experiment. Glycosaminoglycan (GAG) content, collagen content and histopathological evaluation of articular cartilage were also determined at the end of the experiment. SMT reduced mechanical hyperalgesia and the serum levels of IL-1beta, TNF-alpha and nitrite. Further, SMT reduced the loss of GAG from articular cartilage. Microscopically, SMT reduced the severity of the cartilage lesion. The results indicate the effectiveness of SMT in attenuating the pain and pathology of experimental OA phase by reducing the production of nitric oxide and interleukin-1beta and tumor necrosis factor-alpha, which are known to play a major role in the pathophysiology of OA. PMID- 25111193 TI - Assessment of body composition in Indian adults: comparison between dual-energy X ray absorptiometry and isotope dilution technique. AB - Dual-energy X-ray absorptiometry (DXA) and isotope dilution technique have been used as reference methods to validate the estimates of body composition by simple field techniques; however, very few studies have compared these two methods. We compared the estimates of body composition by DXA and isotope dilution (18O) technique in apparently healthy Indian men and women (aged 19-70 years, n 152, 48 % men) with a wide range of BMI (14-40 kg/m2). Isotopic enrichment was assessed by isotope ratio mass spectroscopy. The agreement between the estimates of body composition measured by the two techniques was assessed by the Bland-Altman method. The mean age and BMI were 37 (sd 15) years and 23.3 (sd 5.1) kg/m2, respectively, for men and 37 (sd 14) years and 24.1 (sd 5.8) kg/m2, respectively, for women. The estimates of fat-free mass were higher by about 7 (95 % CI 6, 9) %, those of fat mass were lower by about 21 (95 % CI - 18, - 23) %, and those of body fat percentage (BF%) were lower by about 7.4 (95 % CI - 8.2, - 6.6) % as obtained by DXA compared with the isotope dilution technique. The Bland-Altman analysis showed wide limits of agreement that indicated poor agreement between the methods. The bias in the estimates of BF% was higher at the lower values of BF%. Thus, the two commonly used reference methods showed substantial differences in the estimates of body composition with wide limits of agreement. As the estimates of body composition are method-dependent, the two methods cannot be used interchangeably. PMID- 25111196 TI - Nonsterile glove use in addition to hand hygiene to prevent late-onset infection in preterm infants: randomized clinical trial. AB - IMPORTANCE: Late-onset infections commonly occur in extremely preterm infants and are associated with high rates of mortality and neurodevelopmental impairment. Hand hygiene alone does not always achieve the desired clean hands, as microorganisms are still present more than 50% of the time. We hypothesize that glove use after hand hygiene may further decrease these infections. OBJECTIVE: To determine if nonsterile glove use after hand hygiene before all patient and intravenous catheter contact, compared with hand hygiene alone, prevents late onset infections in preterm infants. DESIGN, SETTINGS, AND PARTICIPANTS: A prospective, single-center, clinical, randomized trial was conducted in infants admitted to the neonatal intensive care unit who weighed less than 1000 g and/or had a gestational age of less than 29 weeks and were less than 8 days old. There were 175 eligible infants, of which 120 were enrolled during a 30-month period from December 8, 2008, to June 20, 2011. INTERVENTIONS: Infants were randomly assigned to receive care with nonsterile gloves after hand hygiene (group A) or care after hand hygiene alone (group B) before all patient and intravenous line (central and peripheral) contact. Study intervention was continued while patients had central or peripheral venous access. MAIN OUTCOMES AND MEASURES: One or more episodes of late-onset (>72 hours of age) infection in the bloodstream, urinary tract, or cerebrospinal fluid or necrotizing enterocolitis. RESULTS: The 2 groups were similar in baseline demographic characteristics. Late-onset invasive infection or necrotizing enterocolitis occurred in 32% of infants (19 of 60) in group A compared with 45% of infants (27 of 60) in group B (difference, -12%; 95% CI, -28% to 6%; P = .13). In group A compared with group B, there were 53% fewer gram-positive bloodstream infections (15% [9 of 60] vs 32% [19 of 60]; difference, -17%; 95% CI, -31% to -1%; P = .03) and 64% fewer central line associated bloodstream infections (3.4 vs 9.4 per 1000 central line days; ratio, 0.36; 95% CI, 0.16 to 0.81; P = .01). CONCLUSIONS AND RELEVANCE: Glove use after hand hygiene prior to patient and line contact is associated with fewer gram positive bloodstream infections and possible central line-associated bloodstream infections in preterm infants. This readily implementable infection control measure may result in decreased infections in high-risk preterm infants. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01729000. PMID- 25111195 TI - Extremely low-frequency electromagnetic fields cause G1 phase arrest through the activation of the ATM-Chk2-p21 pathway. AB - In daily life, humans are exposed to the extremely low-frequency electromagnetic fields (ELF-EMFs) generated by electric appliances, and public concern is increasing regarding the biological effects of such exposure. Numerous studies have yielded inconsistent results regarding the biological effects of ELF-EMF exposure. Here we show that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, inhibiting cell proliferation. To present well-founded results, we comprehensively evaluated the biological effects of ELF-EMFs at the transcriptional, protein, and cellular levels. Human HaCaT cells from an immortalized epidermal keratinocyte cell line were exposed to a 1.5 mT, 60 Hz ELF EMF for 144 h. The ELF-EMF could cause G1 arrest and decrease colony formation. Protein expression experiments revealed that ELF-EMFs induced the activation of the ATM/Chk2 signaling cascades. In addition, the p21 protein, a regulator of cell cycle progression at G1 and G2/M, exhibited a higher level of expression in exposed HaCaT cells compared with the expression of sham-exposed cells. The ELF EMF-induced G1 arrest was diminished when the CHK2 gene expression (which encodes checkpoint kinase 2; Chk2) was suppressed by specific small interfering RNA (siRNA). These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT cells, resulting in cell cycle arrest at the G1 phase. Based on the precise control of the ELF-EMF exposure and rigorous sham-exposure experiments, all transcriptional, protein, and cellular level experiments consistently supported the conclusion. This is the first study to confirm that a specific pathway is triggered by ELF-EMF exposure. PMID- 25111197 TI - Control of single-molecule junction conductance of porphyrins via a transition metal center. AB - Using scanning tunneling microscope break-junction experiments and a new first principles approach to conductance calculations, we report and explain low-bias charge transport behavior of four types of metal-porphyrin-gold molecular junctions. A nonequilibrium Green's function approach based on self-energy corrected density functional theory and optimally tuned range-separated hybrid functionals is developed and used to understand experimental trends quantitatively. Importantly, due to the localized d states of the porphyrin molecules, hybrid functionals are essential for explaining measurements; standard semilocal functionals yield qualitatively incorrect results. Comparing directly with experiments, we show that the conductance can change by nearly a factor of 2 when different metal cations are used, counter to trends expected from gas-phase ionization energies which are relatively unchanged with the metal center. Our work explains the sensitivity of the porphyrin conductance with the metal center via a detailed and quantitative portrait of the interface electronic structure and provides a new framework for understanding transport quantitatively in complex junctions involving molecules with localized d states of relevance to light harvesting and energy conversion. PMID- 25111198 TI - Manganese doped fluorescent paramagnetic nanocrystals for dual-modal imaging. AB - In this work, dual-modal (fluorescence and magnetic resonance) imaging capabilities of water-soluble, low-toxicity, monodisperse Mn-doped ZnSe nanocrystals (NCs) with a size (6.5 nm) below the optimum kidney cutoff limit (10 nm) are reported. Synthesizing Mn-doped ZnSe NCs with varying Mn(2+) concentrations, a systematic investigation of the optical properties of these NCs by using photoluminescence (PL) and time resolved fluorescence are demonstrated. The elemental properties of these NCs using X-ray photoelectron spectroscopy and inductive coupled plasma-mass spectroscopy confirming Mn(2+) doping is confined to the core of these NCs are also presented. It is observed that with increasing Mn(2+) concentration the PL intensity first increases, reaching a maximum at Mn(2+) concentration of 3.2 at% (achieving a PL quantum yield (QY) of 37%), after which it starts to decrease. Here, this high-efficiency sample is demonstrated for applications in dual-modal imaging. These NCs are further made water-soluble by ligand exchange using 3-mercaptopropionic acid, preserving their PL QY as high as 18%. At the same time, these NCs exhibit high relaxivity (~2.95 mM(-1) s(-1)) to obtain MR contrast at 25 degrees C, 3 T. Therefore, the Mn(2+) doping in these water-soluble Cd-free NCs are sufficient to produce contrast for both fluorescence and magnetic resonance imaging techniques. PMID- 25111199 TI - Docetaxel plus oral metronomic cyclophosphamide: a phase II study with pharmacodynamic and pharmacogenetic analyses in castration-resistant prostate cancer patients. AB - BACKGROUND: Docetaxel plus prednisone is currently the standard first-line treatment in metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to assess the clinical activity and pharmacodynamic/pharmacogenetic profile of docetaxel plus prednisone in combination with metronomic cyclophosphamide in mCRPC patients. METHODS: Forty one chemotherapy-naive patients received docetaxel (60 mg/m(2) intravenously every 3 weeks up to 12 cycles) and, from day 2, prednisone 10 mg/day, celecoxib 400 mg/day, and metronomic cyclophosphamide 50 mg/day, continuously. Plasma VEGF and bFGF were detected by ELISA. Real-time PCR-SNP analysis of VEGF gene was performed using an ABI PRISM 7900HT SDS and TaqMan SNP genotyping. RESULTS: Eighty-seven percent of patients were free of progression at 6 months. A decrease in prostate-specific antigen >=50% was observed in 82% of 39 evaluable patients, with a median time to progression of 12.3 months. Grade 3 adverse events were neutropenia (5%), thrombocytopenia, diarrhea, and stomatitis (2.5%). Median PFS and OS were 14.9 months (95% CI, 9.2-15.3 months) and 33.3 months (95% CI, 23 35.6 months), respectively. Of 11 patients (28%) with evaluable disease, 5 (44%) achieved a complete response, 2 (11%) a partial response, and 2 (11%) stable disease, whereas 2 showed disease progression. The -1154A/G VEGF polymorphism, plasma VEGF, and bFGF after the first cycle of chemotherapy may represent useful pharmacodynamic markers to predict better outcomes. CONCLUSIONS: The combination of docetaxel and oral metronomic chemotherapy is effective and well tolerated in mCRPC patients and may deserve further evaluation. PMID- 25111200 TI - Stroke code improves intravenous thrombolysis administration in acute ischemic stroke. AB - BACKGROUND AND PURPOSE: Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with "Stroke Code" (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis. METHODS: The study period was divided into the "pre-SC era" (January 2006 to July 2010) and "SC era" (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras. RESULTS: During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times <=60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale <=2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality. CONCLUSION: The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time. PMID- 25111201 TI - IgY pharmacokinetics in rabbits: implications for IgY use as antivenoms. AB - This paper presents the first study of chicken IgY pharmacokinetics (PK) in rabbits. We measured IgY blood serum concentrations using a specific high sensitivity ELISA method. The fast initial component observed when studying horse Fab, F(ab')2 or IgG was absent from IgY PK. During the first 80 min of observation there was only a single slow exponential decay, which sped up afterward to the point that IgY became undetectable after 216 h of observation; due to this time course, PK parameters were determined with trapezoidal integration. The most significant IgY pharmacokinetic parameters determined were (all presented as medians and their 95% confidence interval): Area Under the Curve = 183.8 (135.2, 221.5) mg.h.L(-1); Distribution volume of the central compartment.[Body Weight (BW)](-1) = 46.0 (21.7, 70.3) mL.kg(-1); Distribution volume in steady state.BW(-1) = 56.8 (44.4, 68.5) mLkg(-1); Mean Residence Time = 40.1 (33.6, 48.5) h; Total plasma clearance.BW(-1) = 1.44 (1.15, 1.66) mL.h( 1).kg(-1). Anti IgY IgG titers determined by ELISA increased steadily after 72 h, and reached 2560 (1920, 5760) dilution(-1) at 264 h; anti-chicken IgG concentrations rose up to 3.19 (2.31, 6.17) MUg/mL in 264 h. Our results show that IgY PK lacks the fast initial decay observed in other PK studies using horse IgG, F(ab')2 or Fab, remains in the body 39.0 (28.7, 47.2) % much as IgG and is ~3 times more immunogenic that horse IgG in rabbits. PMID- 25111202 TI - Kinetics and mechanism of the racemization of aryl allenes catalyzed by cationic gold(I) phosphine complexes. AB - The kinetics of the racemization of aromatic 1,3-disubstituted allenes catalyzed by gold phosphine complexes has been investigated. The rate of gold-catalyzed allene racemization displayed first-order dependence on allene, and catalyst concentration and kinetic analysis of gold-catalyzed allene racemization as a function of allene and phosphine electron-donor ability established the accumulation of electron density on the phosphine atom and the depletion of electron density on the terminal allenyl carbon atoms in the rate-limiting transition state for racemization. These and other observations were in accord with a mechanism for allene racemization involving rapid and reversible inter- and intramolecular allene exchange followed by turnover-limiting, unimolecular conversion of a chiral gold eta(2)-allene complex to an achiral eta(1)-allylic cation intermediate through a bent and twisted eta(1)-allene transition state. With respect to proper ligand selection, these studies reveal that both electron poor phosphine ligands and polar solvents facilitate racemization. PMID- 25111206 TI - Alzheimer disease risk factors. PMID- 25111207 TI - Alzheimer disease risk factors--reply. PMID- 25111208 TI - GNAL mutations and dystonia. PMID- 25111209 TI - GNAL mutations and dystonia--reply. PMID- 25111210 TI - Blood test for variant Creutzfeldt-Jakob disease. PMID- 25111211 TI - Blood test for variant Creutzfeldt-Jakob disease--reply. PMID- 25111212 TI - Elevated serum DDE and risk for Alzheimer disease. PMID- 25111213 TI - Defining the new end point for multiple sclerosis treatment. PMID- 25111214 TI - Elevated serum DDE and risk for Alzheimer disease--reply. PMID- 25111217 TI - Pregnancy post-laparoscopic hysteropexy. PMID- 25111218 TI - Impact of the anesthetic conserving device on respiratory parameters and work of breathing in critically ill patients under light sedation with sevoflurane. AB - BACKGROUND: Sevoflurane sedation in the intensive care unit is possible with a special heat and moisture exchanger called the Anesthetic Conserving Device (ACD) (AnaConDa; Sedana Medical AB, Uppsala, Sweden). The ACD, however, may corrupt ventilatory mechanics when used during the weaning process of intensive care unit patients. The authors compared the ventilatory effects of light-sedation with sevoflurane administered with the ACD and those of classic management, consisting of a heated humidifier and intravenous sedation, in intensive care unit patients receiving pressure-support ventilation. METHODS: Fifteen intensive care unit patients without chronic pulmonary disease were included. A target Richmond Agitation Sedation Scale level of -1/-2 was obtained with intravenous remifentanil (baseline 1-condition). Two successive interventions were tested: replacement of the heated humidifier by the ACD without sedation change (ACD condition) and sevoflurane with the ACD with an identical target level (ACD sevoflurane-condition). Patients finally returned to baseline (baseline 2 condition). Work of breathing, ventilatory patterns, blood gases, and tolerance were recorded. A steady state of 30 min was achieved for each experimental condition. RESULTS: ACD alone worsened ventilatory parameters, with significant increases in work of breathing (from 1.7 +/- 1.1 to 2.3 +/- 1.2 J/l), minute ventilation, P0,1, intrinsic positive end-expiratory pressure (from 1.3 +/- 2.6 to 4.7 +/- 4.2 cm H2O), inspiratory pressure swings, and decreased patient comfort. Sevoflurane normalized work of breathing (from 2.3 +/- 1.2 to 1.8 +/- 1 J/l), intrinsic positive end-expiratory pressure (from 4.7 +/- 4.2 to 1.8 +/- 2 cm H2O), inspiratory pressure swings, other ventilatory parameters, and patient tolerance. CONCLUSIONS: ACD increases work of breathing and worsens ventilatory parameters. Sevoflurane use via the ACD (for a light-sedation target) normalizes respiratory parameters. In this patient's population, light-sedation with sevoflurane and the ACD may be possible during the weaning process. PMID- 25111219 TI - Development and validation of instrumentation to assess perceptions of educational issues for students with cancer. PMID- 25111220 TI - Microvillous atrophy: atypical presentations. AB - OBJECTIVES: Microvillous inclusion disease (MVID) is a cause of intractable diarrhea in infancy. In its classic form, the disease is characterized by a severe persistent watery diarrhea starting within the first days of life. Parenteral nutrition and small bowel transplantation are the only known treatments for the affected children. Histologically, periodic acid-Schiff (PAS) staining shows accumulation of periodic acid-Schiff-positive staining material along the apical pole of enterocytes, whereas transmission electron microscopy exhibits microvillus inclusion bodies within the cytoplasm of enterocytes with rarefied and shortened microvilli and secretory granules. The objective of this work was to explore clinical, morphological, and genetic findings in cases of MVID with unusual presentations. METHODS: Clinical, histological, and genetic findings are reported for 8 cases of MVID with atypical presentation. RESULTS: The diarrhea started after several months in 3 cases. It was usually less abundant and 3 patients were weaned off parenteral nutrition. None required intestinal transplantation. Three patients experienced malformations, dysmorphy, sensory disabilities, and severe mental retardation. One had a hydrocephaly. Three patients had a cholestasis with low gamma-glutamyl transferase levels. Light microscopy showed histological abnormalities consistent with MVID in all of the cases, but the lesions were sometimes focal or delayed. Transmission electron microscopy retrieved some criteria of MVID in 4 patients. Finally, 6 patients were homozygotes or compound heterozygotes for MYO5B mutations. CONCLUSIONS: This study extends the spectrum of MVID to less severe clinical presentations. PMID- 25111221 TI - Breast-feeding improves gut maturation compared with formula feeding in preterm babies. AB - OBJECTIVE: The incidence of necrotizing enterocolitis (NEC) is higher in formula fed babies than in breast-fed babies, which may be caused by breast-feeding induced gut maturation. The effect of breast-feeding on gut maturation has been widely studied in animal models. This study aimed to assess the effects of breast feeding on intestinal maturation in prematurely born babies by evaluating postnatal changes in urinary intestinal fatty acid binding protein (I-FABP) levels, a specific enterocyte marker. METHODS: Gut maturation in 40 premature babies (<37 weeks of gestation) without gastrointestinal morbidity was studied, of whom 21 were exclusively breast-fed and 19 were formula-fed infants. Urinary I FABP levels as the measure of gut maturation were measured at 5, 12, 19, and 26 days after birth. RESULTS: In breast-fed infants, there was a significant increase in median urinary I-FABP levels between 5 and 12 days after birth (104 [78-340] pg/mL to 408 [173-1028] pg/mL, P = 0.002), whereas I-FABP concentration in formula-fed infants increased between 12 and 19 days after birth (105 [44-557] pg/mL, 723 [103-1670] pg/mL, P = 0.004). Breast-fed babies had significantly higher median urinary I-FABP levels at postnatal day 12 (P = 0.01). CONCLUSIONS: The time course of the postnatal increase in urinary I-FABP levels reflecting gut maturation was significantly delayed in formula-fed babies, suggesting a delayed physiological response in formula-fed compared with breast-fed infants. PMID- 25111222 TI - Inflammatory bowel disease in children of Manitoba: 30 years' experience of a tertiary center. AB - OBJECTIVES: The aim of this study was to describe the incidence and prevalence of inflammatory bowel disease (IBD) in children <17 years of age in 30 years from 1978 to 2007. METHODS: From January 1, 1978, to December 31, 2007, the sex- and age-adjusted annual incidence and prevalence of pediatric IBD per 100,000 population were calculated based on the pediatric IBD database of the only pediatric tertiary center in the province. The annual health statistics records for the Province of Manitoba were used to calculate population estimates for the participants. To ensure validity of data, the University of Manitoba IBD Epidemiology Database was analyzed for patients <17 years of age from 1989 to 2000. RESULTS: The sex- and age-adjusted incidence of pediatric Crohn disease has increased from 1.2/100,000 in 1978 to 4.68/100,000 in 2007 (P < 0.001). For ulcerative colitis, the incidence has increased from 0.47/100,000 in 1978 to 1.64/100,000 in 2007 (P < 0.001). During the same time period, the prevalence of Crohn disease has increased from 3.1 to 18.9/100,000 (P < 0.001) and from 0.7 to 12.7/100,000 for ulcerative colitis (P < 0.001). During the last 5 years of the study the average annual incidence of IBD in urban patients was 8.69/100,000 as compared with 4.75/100,000 for rural patients (P < 0.001). CONCLUSIONS: The incidence and prevalence of pediatric IBD are increasing. The majority of patients were residents of urban Manitoba, confirming the important role of environmental factors in the etiopathogenesis of IBD. PMID- 25111223 TI - A 16-Year-Old Boy With Colonic Adenocarcinoma. PMID- 25111224 TI - Psychometric properties of PedsQL generic core scales for children with functional constipation in the Netherlands. AB - OBJECTIVES: The aim of the study was to evaluate the psychometric properties of the Dutch translation of the Pediatric Quality of Life Inventory version 4.0 Generic Core Scales (PedsQL) in children with functional constipation (FC). METHODS: The PedsQL was completed by children with FC ages 5 to 18 years and by the parents of children ages 2 to 18 years. To assess construct validity, all of the parents and children completed the PedsQL Gastrointestinal Symptoms Module (GI module) and children ages 8 to 18 years completed the defecation disorder list. Item response distributions, internal consistency reliability, patient parent agreement, and discriminating ability were evaluated. RESULTS: Overall, 269 children were enrolled. The PedsQL showed minimal missing responses (self report: 5.3% with >50% missing, parent report: 2.6% with >50% missing) and achieved satisfactory internal consistency for the total (self-report: alpha = 0.86, parent report: alpha = 0.88), physical health (self-report: alpha = 0.75, parent report alpha = 0.83), and psychosocial health (self-report: alpha = 0.80; parent report: alpha = 0.85) scores. Internal consistency was less convincing for those ages 5 to 7 years (alpha = 0.53-0.77) than for older individuals. Self reported health-related quality of life was lower than parent reported, with the exception of children ages 5 to 7 years. Interrater reliability intraclass correlations were 0.52 to 0.61 for the overall population. Correlations among the PedsQL, GI module, and defecation disorder list were consistent with a priori hypotheses and generally supported construct validity. The PedsQL distinguished between a previously published healthy reference sample and children with FC, and between those with mild and severe symptoms (P < 0.05). CONCLUSIONS: The self reported and proxy reported PedsQL demonstrated satisfactory measurement properties in Dutch children with FC ages 8 to 18 years. Further research is needed to establish internal consistency and validity in those ages 5 to 7 years. PMID- 25111225 TI - Scanning the scars: the utility of transient elastography in young children. PMID- 25111226 TI - Thrombospondin-1 deficiency causes a shift from fibroproliferative to inflammatory kidney disease and delays onset of renal failure. AB - Thrombospondin-1 (TSP1) is a multifunctional matricellular protein known to promote progression of chronic kidney disease. To gain insight into the underlying mechanisms through which TSP1 accelerates chronic kidney disease, we compared disease progression in Col4a3 knockout (KO) mice, which develop spontaneous kidney failure, with that of Col4a3;Tsp1 double-knockout (DKO) mice. Decline of excretory renal function was significantly delayed in the absence of TSP1. Although Col4a3;Tsp1 DKO mice did progress toward end-stage renal failure, their kidneys exhibited distinct histopathological lesions, compared with creatinine level-matched Col4a3 KO mice. Although kidneys of both Col4a3 KO and Col4a3;Tsp1 DKO mice exhibited a widened tubulointerstitium, predominant lesions in Col4a3 KO kidneys were collagen deposition and fibroblast accumulation, whereas in Col4a3;Tsp1 DKO kidney inflammation was predominant, with less collagen deposition. Altered disease progression correlated with impaired activation of transforming growth factor-beta1 (TGF-beta1) in vivo and in vitro in the absence of TSP1. In summary, our findings suggest that TSP1 contributes to progression of chronic kidney disease by catalyzing activation of latent TGF beta1, resulting in promotion of a fibroproliferative response over an inflammatory response. Furthermore, the findings suggest that fibroproliferative and inflammatory lesions are independent entities, both of which contribute to decline of renal function. PMID- 25111227 TI - Mutations in pre-mRNA processing factors 3, 8, and 31 cause dysfunction of the retinal pigment epithelium. AB - Mutations in the ubiquitously expressed pre-mRNA processing factors 3, 8, and 31 (PRPF3, PRPF8, and PRPF31) cause nonsyndromic dominant retinitis pigmentosa in humans, an inherited retinal degeneration. It is unclear what mechanisms, or which cell types of the retina, are affected. Transgenic mice with the human mutations in these genes display late-onset morphological changes in the retinal pigment epithelium (RPE). To determine whether the observed morphological changes are preceded by abnormal RPE function, we investigated its phagocytic function in Prpf3(T494M/T494M), Prpf8(H2309P/H2309P), and Prpf31(+/-) mice. We observe decreased phagocytosis in primary RPE cultures from mutant mice, and this is replicated by shRNA-mediated knockdown of PRPF31 in human ARPE-19 cells. The diurnal rhythmicity of phagocytosis is almost lost, indicated by the marked attenuation of the phagocytic burst 2 hours after light onset. The strength of adhesion between RPE apical microvilli and photoreceptor outer segments also declined during peak adhesion in all mutants. In all models, at least one of the receptors involved in binding and internalization of shed photoreceptor outer segments was subjected to changes in localization. Although the mechanism underlying these changes in RPE function is yet to be elucidated, these data are consistent with the mouse RPE being the primary cell affected by mutations in the RNA splicing factors, and these changes occur at an early age. PMID- 25111228 TI - Silencing of drpr leads to muscle and brain degeneration in adult Drosophila. AB - Mutations in the gene encoding the single transmembrane receptor multiple epidermal growth factor-like domain 10 (MEGF10) cause an autosomal recessive congenital muscle disease in humans. Although mammalian MEGF10 is expressed in the central nervous system as well as in skeletal muscle, patients carrying mutations in MEGF10 do not show symptoms of central nervous system dysfunction. drpr is the sole Drosophila homolog of the human genes MEGF10, MEGF11, and MEGF12 (JEDI, PEAR). The functional domains of MEGF10 and drpr bear striking similarities, and residues affected by MEGF10 mutations in humans are conserved in drpr. Our analysis of drpr mutant flies revealed muscle degeneration with fiber size variability and vacuolization, as well as reduced motor performance, features that have been observed in human MEGF10 myopathy. Vacuolization was also seen in the brain. Tissue-specific RNAi experiments demonstrated that drpr deficiency in muscle, but not in the brain, leads to locomotor defects. The histological and behavioral abnormalities seen in the affected flies set the stage for further studies examining the signaling pathway modulated by MEGF10/Drpr in muscle, as well as assessing the effects of genetic and/or pharmacological manipulations on the observed muscle defects. In addition, the absence of functional redundancy for Drpr in Drosophila may help elucidate whether paralogs of MEGF10 in humans (eg, MEGF11) contribute to maintaining wild type function in the human brain. PMID- 25111229 TI - CREB-induced inflammation is important for malignant mesothelioma growth. AB - Malignant mesothelioma (MM) is an aggressive tumor with no treatment regimen. Previously we have demonstrated that cyclic AMP response element binding protein (CREB) is constitutively activated in MM tumor cells and tissues and plays an important role in MM pathogenesis. To understand the role of CREB in MM tumor growth, we generated CREB-inhibited MM cell lines and performed in vitro and in vivo experiments. In vitro experiments demonstrated that CREB inhibition results in significant attenuation of proliferation and drug resistance of MM cells. CREB silenced MM cells were then injected into severe combined immunodeficiency mice, and tumor growth in s.c. and i.p. models of MM was followed. We observed significant inhibition in MM tumor growth in both s.c. and i.p. models and the presence of a chemotherapeutic drug, doxorubicin, further inhibited MM tumor growth in the i.p. model. Peritoneal lavage fluids from CREB-inhibited tumor bearing mice showed a significantly reduced total cell number, differential cell counts, and pro-inflammatory cytokines and chemokines (IL-6, IL-8, regulated on activation normal T cell expressed and secreted, monocyte chemotactic protein-1, and vascular endothelial growth factor). In vitro studies showed that asbestos induced inflammasome/inflammation activation in mesothelial cells was CREB dependent, further supporting the role of CREB in inflammation-induced MM pathogenesis. In conclusion, our data demonstrate the involvement of CREB in the regulation of MM pathogenesis by regulation of inflammation. PMID- 25111230 TI - Sphingosine-1-phosphate mediates a reciprocal signaling pathway between stellate cells and cancer cells that promotes pancreatic cancer growth. AB - Sphingosine-1-phosphate (S1P) is produced by sphingosine kinase 1 and is implicated in tumor growth, although the mechanisms remain incompletely understood. Pancreatic stellate cells (PSCs) reside within the tumor microenvironment and may regulate tumor progression. We hypothesized that S1P activates PSCs to release paracrine factors, which, in turn, increase cancer cell invasion and growth. We used a combination of human tissue, in vitro, and in vivo studies to mechanistically evaluate this concept. Sphingosine kinase 1 was overexpressed in human pancreatic tissue, especially within tumor cells. S1P activated PSCs in vitro and conditioned medium from S1P-stimulated PSCs, increased pancreatic cancer cell migration, and invasion, which was dependent on S1P2, ABL1 (alias c-Abl) kinase, and matrix metalloproteinase-9. In vivo studies showed that pancreatic cancer cells co-implanted with S1P2 receptor knockdown PSCs led to less cancer growth and metastasis in s.c. and orthotopic pancreatic cancer models compared with control PSCs. Pancreatic cancer cell-derived S1P activates PSCs to release paracrine factors, including matrix metalloproteinase 9, which reciprocally promotes tumor cell migration and invasion in vitro and cancer growth in vivo. PMID- 25111231 TI - Comparative urease enzyme inhibition profile of leaves and stems of Rumex nervosus vahl. AB - Ureases inhibitory agents are becoming important because of their application in treating many aliments. This work describes the urease inhibitory potential of the crude extracts of leaves and stems of Rumex nervosus, which includes crude extracts as well as various sub-fractions, n-hexane, chloroform, ethyl acetate and methanol. The crude extracts of stems and leaves exhibited promising ureases inhibition (IC50 values of 17.5 +/- 0.84 and 29.6 +/- 0.96 MUg/mL, respectively). Among the sub-fractions, methanol-soluble fractions of leaves and stems showed significant inhibition having IC50 values of 21.9 +/- 0.67 and 21.5 +/- 0.69 MUg/mL, respectively, followed by ethyl acetate fractions of stems and leaves. PMID- 25111233 TI - Psychological stress increases risk for peptic ulcer, regardless of Helicobacter pylori infection or use of nonsteroidal anti-inflammatory drugs. AB - BACKGROUND & AIMS: There is controversy over whether psychological stress contributes to development of peptic ulcers. We collected data on features of life stress and ulcer risk factors from a defined population in Denmark and compared these with findings of confirmed ulcers during the next 11-12 years. METHODS: We collected blood samples and psychological, social, behavioral, and medical data in 1982-1983 from a population-based sample of 3379 Danish adults without a history of ulcer participating in the World Health Organization's MONICA study. A 0- to 10-point stress index scale was used to measure stress on the basis of concrete life stressors and perceived distress. Surviving eligible participants were reinterviewed in 1987-1988 (n = 2809) and 1993-1994 (n = 2410). Ulcer was diagnosed only for patients with a distinct breach in the mucosa. All diagnoses were confirmed by review of radiologic and endoscopic reports. Additional cases of ulcer were detected in a search of all 3379 subjects in the Danish National Patient Register. RESULTS: Seventy-six subjects were diagnosed with ulcer. On the basis of the stress index scale, ulcer incidence was significantly higher among subjects in the highest tertile of stress scores (3.5%) than the lowest tertile (1.6%) (adjusted odds ratio, 2.2; 95% confidence interval [CI], 1.2-3.9; P < .01). The per-point odds ratio for the stress index (1.19; 95% CI, 1.09-1.31; P < .001) was unaffected after adjusting for the presence of immunoglobulin G antibodies against Helicobacter pylori in stored sera, alcohol consumption, or sleep duration but lower after adjusting for socioeconomic status (1.17; 95% CI, 1.07-1.29; P < .001) and still lower after further adjustments for smoking, use of nonsteroidal anti-inflammatory drugs, and lack of exercise (1.11; 95% CI, 1.01-1.23; P = .04). The risk for ulcer related to stress was similar among subjects who were H pylori seropositive, those who were H pylori seronegative, and those exposed to neither H pylori nor nonsteroidal anti-inflammatory drugs. On multivariable analysis, stress, socioeconomic status, smoking, H pylori infection, and use of nonsteroidal anti inflammatory drugs were independent predictors of ulcer. CONCLUSIONS: In a prospective study of a population-based Danish cohort, psychological stress increased the incidence of peptic ulcer, in part by influencing health risk behaviors. Stress had similar effects on ulcers associated with H pylori infection and those unrelated to either H pylori or use of nonsteroidal anti inflammatory drugs. PMID- 25111232 TI - Comparative molecular dynamics simulation of Hepatitis C Virus NS3/4A protease (Genotypes 1b, 3a and 4b) predicts conformational instability of the catalytic triad in drug resistant strains. AB - The protease domain of the Hepatitis C Virus (HCV) nonstructural protein 3 (NS3) has been targeted for inhibition by several direct-acting antiviral drugs. This approach has had marked success to treat infections caused by HCV genotype 1 predominant in the USA, Europe, and Japan. However, genotypes 3 and 4, dominant in developing countries, are resistant to a number of these drugs and little progress has been made towards understanding the structural basis of their drug resistivity. We have previously developed a 4D computational methodology, based on 3D structure modeling and molecular dynamics simulation, to analyze the active sites of the NS3 proteases of HCV-1b and 4a in relation to their catalytic activity and drug susceptibility. Here, we improved the methodology, extended the analysis to include genotype 3a (predominant in South Asia including Pakistan), and compared the results of the three genotypes (1b, 3a and 4a). The 4D analyses of the interactions between the catalytic triad residues (His57, Asp81, and Ser139) indicate conformational instability of the catalytic site in HCV-3a and 4a compared to that of HCV-1b NS3 protease. The divergence is gradual and genotype-dependent, with HCV-1b being the most stable, HCV-4a being the most unstable and HCV-3a representing an intermediate state. These results suggest that the structural dynamics behavior, more than the rigid structure, could be related to the altered catalytic activity and drug susceptibility seen in NS3 proteases of HCV-3a and 4a. PMID- 25111235 TI - Training directors have positive perceptions of a competency-based gastroenterology and transplant hepatology fellowship program. AB - BACKGROUND & AIMS: In 2012, the American Board of Internal Medicine approved a pilot competency-based transplant hepatology (TH) training program. This program allows gastroenterology (GI) and TH fellowships to be completed in 3 years. We investigated the perceptions and beliefs of GI and TH division and fellowship program directors on the competency-based TH training program. METHODS: All current GI and TH division and fellowship program directors from the 162 fellowship programs accredited by the Accreditation Council for Graduate Medical Education were invited via e-mail to anonymously complete the online survey. The survey questioned their perceptions of the 3-year combined GI and TH training program. RESULTS: A total of 116 participants completed the survey (~38% response rate). Most respondents were GI fellowship directors (61%); 15% were GI and hepatology division directors, 19% were TH fellowship directors, 14% were TH division directors, and 5% were GI division directors. Most of the respondents were in favor of the pilot program (85%). Only 63% of all respondents believed that graduates of the pilot program would achieve the same level of competency in GI as those who completed the traditional program. Overall, 71% believed incorporation of the 3-year training model would increase interest and participation in TH fellowships. CONCLUSIONS: Most of the academic GI and TH division and fellowship program directors embrace competency-based fellowship education and TH subspecialty training during the designated 3-year GI fellowship. Future studies will be needed to reevaluate these beliefs after several years. PMID- 25111234 TI - Clinical and histologic features of azithromycin-induced liver injury. AB - BACKGROUND & AIMS: Rare cases of azithromycin-induced hepatotoxicity have been reported, with variable clinical and histologic features. We characterized clinical features and outcomes of azithromycin-induced liver injury. METHODS: We identified patients with azithromycin-induced liver injury from the Drug-Induced Liver Injury Network Prospective Study who had causality scores of definite, highly likely, or probable. Demographic, clinical, and laboratory data and 6 month outcomes were examined. RESULTS: Eighteen patients (72% female; mean age, 37 y) had causality scores of definite (n = 1), highly likely (n = 9), or probable (n = 8). Common presenting symptoms were jaundice, abdominal pain, nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were first detected 14 days after azithromycin cessation (range, 9-20 d). The median duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in 2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver histology showed ductopenia and veno-occlusive changes in a few patients. Two individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8 patients had recovered, 4 patients had chronic injury, 1 patient died, and 1 patient underwent liver transplantation (outcomes were unavailable for 4 patients). Two of the patients who died or underwent liver transplantation had underlying chronic liver disease. CONCLUSIONS: Azithromycin-induced liver injury occurs within 1 to 3 weeks after azithromycin initiation and predominantly is hepatocellular in nature. Although most patients recover fully, severe cutaneous reactions, chronic injury, and serious complications leading to death or liver transplantation can occur (ClinicalTrials.gov identifier, NCT00345930). PMID- 25111237 TI - Electrochemical quantification of the antioxidant capacity of medicinal plants using biosensors. AB - The working area of a screen-printed electrode, SPE, was modified with the enzyme tyrosinase (Tyr) using different immobilization methods, namely entrapment with water-soluble polyvinyl alcohol (PVA), cross-linking using glutaraldehyde (GA), and cross-linking using GA and human serum albumin (HSA); the resulting electrodes were termed SPE/Tyr/PVA, SPE/Tyr/GA and SPE/Tyr/HSA/GA, respectively. These biosensors were characterized by means of amperometry and EIS techniques. From amperometric evaluations, the apparent Michaelis-Menten constant, Km', of each biosensor was evaluated while the respective charge transfer resistance, Rct, was assessed from impedance measurements. It was found that the SPE/Tyr/GA had the smallest Km' (57 +/- 7) uM and Rct values. This electrode also displayed both the lowest detection and quantification limits for catechol quantification. Using the SPE/Tyr/GA, the Trolox Equivalent Antioxidant Capacity (TEAC) was determined from infusions prepared with "mirto" (Salvia microphylla), "hHierba dulce" (Lippia dulcis) and "salve real" (Lippia alba), medicinal plants commonly used in Mexico. PMID- 25111238 TI - An adaptive jitter mechanism for reactive route discovery in sensor networks. AB - This paper analyses the impact of jitter when applied to route discovery in reactive (on-demand) routing protocols. In multi-hop non-synchronized wireless networks, jitter--a small, random variation in the timing of message emission--is commonly employed, as a means to avoid collisions of simultaneous transmissions by adjacent routers over the same channel. In a reactive routing protocol for sensor and ad hoc networks, jitter is recommended during the route discovery process, specifically, during the network-wide flooding of route request messages, in order to avoid collisions. Commonly, a simple uniform jitter is recommended. Alas, this is not without drawbacks: when applying uniform jitter to the route discovery process, an effect called delay inversion is observed. This paper, first, studies and quantifies this delay inversion effect. Second, this paper proposes an adaptive jitter mechanism, designed to alleviate the delay inversion effect and thereby to reduce the route discovery overhead and (ultimately) allow the routing protocol to find more optimal paths, as compared to uniform jitter. This paper presents both analytical and simulation studies, showing that the proposed adaptive jitter can effectively decrease the cost of route discovery and increase the path quality. PMID- 25111236 TI - Liver involvement in early autosomal-dominant polycystic kidney disease. AB - BACKGROUND & AIMS: Polycystic liver disease (PLD), the most common extrarenal manifestation of autosomal-dominant polycystic kidney disease (ADPKD), has become more prevalent as a result of increased life expectancy, improved renal survival, reduced cardiovascular mortality, and renal replacement therapy. No studies have fully characterized PLD in large cohorts. We investigated whether liver and cyst volumes are associated with volume of the hepatic parenchyma, results from liver laboratory tests, and patient-reported outcomes. METHODS: We performed a cross sectional analysis of baseline liver volumes, measured by magnetic resonance imaging, and their association with demographics, results from liver laboratory and other tests, and quality of life. The data were collected from a randomized, placebo-controlled trial underway at 7 tertiary-care medical centers to determine whether the combination of an angiotensin I-converting enzyme inhibitor and angiotensin II-receptor blocker was superior to the inhibitor alone, and whether low blood pressure (<110/75 mm Hg) was superior to standard blood pressure (120 130/70-80 mm Hg), in delaying renal cystic progression in 558 patients with ADPKD, stages 1 and 2 chronic kidney disease, and hypertension (age, 15-49 y). RESULTS: We found hepatomegaly to be common among patients with ADPKD. Cysts and parenchyma contributed to hepatomegaly. Cysts were more common and liver and cyst volumes were greater in women, increasing with age. Patients with advanced disease had a relative loss of liver parenchyma. We observed small abnormalities in results from liver laboratory tests, and that splenomegaly and hypersplenism were associated with PLD severity. Higher liver volumes were associated with a lower quality of life. CONCLUSIONS: Hepatomegaly is common even in early stage ADPKD and is not accounted for by cysts alone. Parenchymal volumes were larger, compared with liver volumes of patients without ADPKD or with those predicted by standardized equations, even among patients without cysts. The severity of PLD was associated with altered biochemical and hematologic features, as well as quality of life. ClinicalTrials.gov identifier: NCT00283686. PMID- 25111239 TI - Colorimetric detection of Ehrlichia canis via nucleic acid hybridization in gold nano-colloids. AB - Canine monocytic ehrlichiosis (CME) is a major thick-bone disease of dog caused by Ehrlichia canis. Detection of this causal agent outside the laboratory using conventional methods is not effective enough. Thus an assay for E. canis detection based on the p30 outer membrane protein gene was developed. It was based on the p30 gene amplification using loop-mediated isothermal DNA amplification (LAMP). The primer set specific to six areas within the target gene were designed and tested for their sensitivity and specificity. Detection of DNA signals was based on modulation of gold nanoparticles' surface properties and performing DNA/DNA hybridization using an oligonucleotide probe. Presence of target DNA affected the gold colloid nanoparticles in terms of particle aggregation with a plasmonic color change of the gold colloids from ruby red to purple, visible by the naked eye. All the assay steps were completed within 90 min including DNA extraction without relying on standard laboratory facilities. This method was very specific to target bacteria. Its sensitivity with probe hybridization was sufficient to detect 50 copies of target DNA. This method should provide an alternative choice for point of care control and management of the disease. PMID- 25111240 TI - Genotyping single nucleotide polymorphisms using different molecular beacon multiplexed within a suspended core optical fiber. AB - We report a novel approach to genotyping single nucleotide polymorphisms (SNPs) using molecular beacons in conjunction with a suspended core optical fiber (SCF). Target DNA sequences corresponding to the wild- or mutant-type have been accurately recognized by immobilizing two different molecular beacons on the core of a SCF. The two molecular beacons differ by one base in the loop-probe and utilize different fluorescent indicators. Single-color fluorescence enhancement was obtained when the immobilized SCFs were filled with a solution containing either wild-type or mutant-type sequence (homozygous sample), while filling the immobilized SCF with solution containing both wild- and mutant-type sequences resulted in dual-color fluorescence enhancement, indicating a heterozygous sample. The genotyping was realized amplification-free and with ultra low-volume for the required DNA solution (nano-liter). This is, to our knowledge, the first genotyping device based on the combination of optical fiber and molecular beacons. PMID- 25111241 TI - Resource optimization scheme for multimedia-enabled wireless mesh networks. AB - Wireless mesh networking is a promising technology that can support numerous multimedia applications. Multimedia applications have stringent quality of service (QoS) requirements, i.e., bandwidth, delay, jitter, and packet loss ratio. Enabling such QoS-demanding applications over wireless mesh networks (WMNs) require QoS provisioning routing protocols that lead to the network resource underutilization problem. Moreover, random topology deployment leads to have some unused network resources. Therefore, resource optimization is one of the most critical design issues in multi-hop, multi-radio WMNs enabled with multimedia applications. Resource optimization has been studied extensively in the literature for wireless Ad Hoc and sensor networks, but existing studies have not considered resource underutilization issues caused by QoS provisioning routing and random topology deployment. Finding a QoS-provisioned path in wireless mesh networks is an NP complete problem. In this paper, we propose a novel Integer Linear Programming (ILP) optimization model to reconstruct the optimal connected mesh backbone topology with a minimum number of links and relay nodes which satisfies the given end-to-end QoS demands for multimedia traffic and identification of extra resources, while maintaining redundancy. We further propose a polynomial time heuristic algorithm called Link and Node Removal Considering Residual Capacity and Traffic Demands (LNR-RCTD). Simulation studies prove that our heuristic algorithm provides near-optimal results and saves about 20% of resources from being wasted by QoS provisioning routing and random topology deployment. PMID- 25111242 TI - High temperature, high power piezoelectric composite transducers. AB - Piezoelectric composites are a class of functional materials consisting of piezoelectric active materials and non-piezoelectric passive polymers, mechanically attached together to form different connectivities. These composites have several advantages compared to conventional piezoelectric ceramics and polymers, including improved electromechanical properties, mechanical flexibility and the ability to tailor properties by using several different connectivity patterns. These advantages have led to the improvement of overall transducer performance, such as transducer sensitivity and bandwidth, resulting in rapid implementation of piezoelectric composites in medical imaging ultrasounds and other acoustic transducers. Recently, new piezoelectric composite transducers have been developed with optimized composite components that have improved thermal stability and mechanical quality factors, making them promising candidates for high temperature, high power transducer applications, such as therapeutic ultrasound, high power ultrasonic wirebonding, high temperature non destructive testing, and downhole energy harvesting. This paper will present recent developments of piezoelectric composite technology for high temperature and high power applications. The concerns and limitations of using piezoelectric composites will also be discussed, and the expected future research directions will be outlined. PMID- 25111244 TI - Improved ionization energies for the two isomers of phenylpropargyl radical. AB - The ionization of two resonantly stabilized radicals, namely 1-phenylpropargyl (1PPR) and 3-phenylpropargyl (3PPR) are reinvestigated applying vacuum ultraviolet synchrotron radiation and threshold photoelectron spectroscopy. Ionization energies of 7.24+/-0.02 and 7.25+/-0.01 eV are obtained for 1 and 3PPR respectively, which compare well with ab initio calculations. The quality of the spectra are significantly improved mostly due to the application of a new high photon-flux grating available at the VUV-beamline of Swiss Light Source. Resolved vibrational features are assigned according to a Franck-Condon approach. PMID- 25111243 TI - 3beta-Acetyl tormentic acid reverts MRP1/ABCC1 mediated cancer resistance through modulation of intracellular levels of GSH and inhibition of GST activity. AB - ABC transporter overexpression is an important mechanism of multidrug resistance (MDR) and one of the main obstacles to successful cancer treatment. As these proteins actively remove chemotherapeutics from the tumor cells, the pharmacological inhibition of their activity is a possible strategy to revert drug resistance. Moreover, the ability of MDR inhibitors to sensitize resistant cells to conventional drugs is important for their clinical use. Evidence has shown that the multidrug resistance protein 1 (MRP1/ABCC1) is a negative prognostic marker in patients with lung, gastric, or breast cancers or neuroblastoma. Previous data have shown that 3beta-acetyl tormentic acid (3ATA) inhibits the transport activity of the protein MRP1/ABCC1. In this study, we evaluated the ability of 3ATA to sensitize an MDR cell line (GLC4/ADR), which overexpresses MRP1, and investigated the anti-MRP1 mechanisms activated by 3ATA. The results showed that 3ATA is able to reverse the resistance of the MDR cell line to doxorubicin and vincristine, two drugs that are commonly used in cancer chemotherapy. Regarding the sensitizing mechanism induced by 3ATA, this work shows that the triterpene does not modulate the expression of MRP1/ABCC1 but is able to reduce total intracellular glutathione (GSH) levels and decrease the activity of glutathione-s-transferase (GST), the enzyme responsible for the glutathione conjugation of xenobiotics. Together, these results show that 3ATA sensitizes the MDR cell line overexpressing MRP1/ABCC1 to antineoplastic drugs and that this effect is mediated by the modulation of intracellular levels of GSH and GST activity. PMID- 25111245 TI - A barium based coordination polymer for the activity assay of deoxyribonuclease I. AB - A new coordination polymer which shows an unusual 2D inorganic connectivity was constructed. This compound exhibits distinct fluorescence quenching ability to the dye-labeled single-stranded DNA probes with different lengths, based on which an analytical method was developed for the activity assay of deoxyribonuclease I. PMID- 25111246 TI - Highly-efficient synthesis of covalent porphyrinic cages via DABCO-templated imine condensation reactions. AB - We report a new approach to construct covalent porphyrinic cages with different spacer lengths, in which the cage compounds have been conveniently synthesized in quantitative yields, via DABCO-templated imine condensation reactions. PMID- 25111247 TI - The effect of therapeutic hypothermia after cardiopulmonary resuscitation on ICAM 1 and NSE levels in sudden cardiac arrest rabbits. AB - PURPOSE: To assess the effects of hypothermia and normothermia treatments for sudden cardiac arrest (SCA) on brain injury recovery in rabbit models. METHODS: Cardiopulmonary resuscitation (CPR) was implemented on apnea-induced SCA rabbit models. Fifty survived rabbits were then randomly received hypothermia (n = 25, 32-34 degrees C) or normothermia treatment (n = 25, 39-39.5 degrees C) for 12 hours. The expected body temperatures were achieved within the first two hours, maintained for ten hours and then rewarmed. The physiological parameters, neurologic function, and the levels of adhesion molecule ICAM-1 and neuron specific enolase (NSE) were monitored. RESULTS: Hypothermia-treated rabbits had lower heart rate when achieving hypothermia (p < 0.0001) and higher SjvO2 after hypothermia maintenance (p = 0.038). The hypothermia group achieved better brain recovery performance according to the neurological deficit grading scale. ICAM-1 and NSE levels in both serum and CSF of the hypothermia group were lower than the normothemia group (all p < 0.0001) during hypothermia maintenance. CONCLUSION: Hypothermia treatment after CPR provides better outcome than normothermia treatment in SCA rabbits. Hypothermia can reduce the ICAM-1 and NSE levels in both serum and cerebrospinal fluid (CSF). This study supports the clinical implementation of hypothermia treatment for SCA and reveals that ICAM-1 and NSE are involved in the recovery of brain function after resuscitation. PMID- 25111248 TI - How "situational" is judgment in situational judgment tests? AB - Whereas situational judgment tests (SJTs) have traditionally been conceptualized as low-fidelity simulations with an emphasis on contextualized situation descriptions and context-dependent knowledge, a recent perspective views SJTs as measures of more general domain (context-independent) knowledge. In the current research, we contrasted these 2 perspectives in 3 studies by removing the situation descriptions (i.e., item stems) from SJTs. Across studies, the traditional contextualized SJT perspective was not supported for between 43% and 71% of the items because it did not make a significant difference whether the situation description was included or not for these items. These results were replicated across construct domains, samples, and response instructions. However, there was initial evidence that judgment in SJTs was more situational when (a) items measured job knowledge and skills and (b) response options denoted context specific rules of action. Verbal protocol analyses confirmed that high scorers on SJTs without situation descriptions relied upon general rules about the effectiveness of the responses. Implications for SJT theory, research, and design are discussed. PMID- 25111249 TI - Modeling time-lagged reciprocal psychological empowerment-performance relationships. AB - Employee psychological empowerment is widely accepted as a means for organizations to compete in increasingly dynamic environments. Previous empirical research and meta-analyses have demonstrated that employee psychological empowerment is positively related to several attitudinal and behavioral outcomes including job performance. While this research positions psychological empowerment as an antecedent influencing such outcomes, a close examination of the literature reveals that this relationship is primarily based on cross sectional research. Notably, evidence supporting the presumed benefits of empowerment has failed to account for potential reciprocal relationships and endogeneity effects. Accordingly, using a multiwave, time-lagged design, we model reciprocal relationships between psychological empowerment and job performance using a sample of 441 nurses from 5 hospitals. Incorporating temporal effects in a staggered research design and using structural equation modeling techniques, our findings provide support for the conventional positive correlation between empowerment and subsequent performance. Moreover, accounting for the temporal stability of variables over time, we found support for empowerment levels as positive influences on subsequent changes in performance. Finally, we also found support for the reciprocal relationship, as performance levels were shown to relate positively to changes in empowerment over time. Theoretical and practical implications of the reciprocal psychological empowerment-performance relationships are discussed. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID- 25111250 TI - The contextualized self: how team-member exchange leads to coworker identification and helping OCB. AB - This article develops the argument that team-member exchange (TMX) relationships operate at both between- and within-group levels of analysis to influence an employee's sense of identification with coworkers in the group and their helping organizational citizenship behavior (OCB) directed at coworkers. Specifically, we propose that relatively higher quality TMX relationships of an employee as compared with other members of the group influence an employee's sense of positive uniqueness, whereas higher average level of TMX quality in the group creates a greater sense of belonging. Multilevel modeling analysis of field data from 236 bank managers and their subordinates supports the hypotheses and demonstrates 3 key findings. First, team members identify more with their coworkers when they have high relative TMX quality compared with other group members and are also embedded in groups with higher average TMX. Second, identification with coworkers is positively related to helping OCB directed toward team members. Finally, identification with coworkers mediates the interactive effect of relative TMX quality and group average TMX quality on helping. When TMX group relations allow individuals to feel a valued part of the group, but still unique, they engage in higher levels of helping. Overall moderated mediation analysis demonstrates that the mediated relationship linking relative TMX quality with helping OCB via identification with coworkers is stronger when group average TMX is high, but not present when group average TMX is low. We discuss theoretical and practical implications and recommend future research on multilevel conceptualizations of TMX. PMID- 25111251 TI - Beyond the individual victim: multilevel consequences of abusive supervision in teams. AB - We conceptualize a multilevel framework that examines the manifestation of abusive supervision in team settings and its implications for the team and individual members. Drawing on Hackman's (1992) typology of ambient and discretionary team stimuli, our model features team-level abusive supervision (the average level of abuse reported by team members) and individual-level abusive supervision as simultaneous and interacting forces. We further draw on team-relevant theories of social influence to delineate two proximal outcomes of abuse-members' organization-based self-esteem (OBSE) at the individual level and relationship conflict at the team level-that channel the independent and interactive effects of individual- and team-level abuse onto team members' voice, team-role performance, and turnover intentions. Results from a field study and a scenario study provided support for these multilevel pathways. We conclude that abusive supervision in team settings holds toxic consequences for the team and individual, and offer practical implications as well as suggestions for future research on abusive supervision as a multilevel phenomenon. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID- 25111252 TI - "Well, I'm tired of tryin'!" Organizational citizenship behavior and citizenship fatigue. AB - This study seeks to identify workplace conditions that influence the degree to which employees feel worn out, tired, or on edge attributed to engaging in organizational citizenship behavior (OCB) and also how this phenomenon, which we refer to as citizenship fatigue, is associated with future occurrences of OCB. Using data collected from 273 employees and their peers at multiple points in time, we found that the relationship between OCB and citizenship fatigue depends on levels of perceived organizational support, quality of team-member exchange relationships, and pressure to engage in OCB. Specifically, the relationship between OCB and citizenship fatigue is significantly stronger and positive when perceived organizational support is low, and it is significantly stronger and negative when the quality of team-member exchange is high and pressure to engage in OCB is low. Our results also indicate that citizenship fatigue is negatively related to subsequent acts of OCB. Finally, supplemental analyses reveal that the relationship between OCB and citizenship fatigue may vary as a function of the specific facet of OCB. We conclude with a discussion of the key theoretical and practical implications of our findings. PMID- 25111253 TI - Electronic control of ligand-binding preference of a myoglobin mutant. AB - The L29F mutant of sperm whale myoglobin (Mb), where the leucine 29 residue was replaced by phenylalanine (Phe), was shown to exhibit remarkably high affinity to oxygen (O2), possibly due to stabilization of the heme Fe atom-bound O2 in the mutant protein through a proposed unique electrostatic interaction with the introduced Phe29, in addition to well-known hydrogen bonding with His64 [Carver, T. E.; Brantley, R. E.; Singleton, E. W.; Arduini, R. M.; Quillin, M. L.; Phillips, G. N., Jr.; Olson, J. S. J. Biol. Chem., 1992, 267, 14443-14450]. We analyzed the O2 and carbon monoxide (CO) binding properties of the L29F mutant protein reconstituted with chemically modified heme cofactors possessing a heme Fe atom with various electron densities, to determine the effect of a change in the electron density of the heme Fe atom (rho(Fe)) on the O2 versus CO discrimination. The study demonstrated that the preferential binding of O2 over CO by the protein was achieved through increasing rho(Fe), and the ordinary ligand-binding preference, that is, the preferential binding of CO over O2, by the protein was achieved through decreasing rho(Fe). Thus, the O2 and CO binding preferences of the L29F mutant protein could be controlled through electronic modulation of intrinsic heme Fe reactivity through a change in rho(Fe). The present study highlighted the significance of the tuning of the intrinsic heme Fe reactivity through the heme electronic structure in functional regulation of Mb. PMID- 25111254 TI - Solvent-assisted lipid bilayer formation on silicon dioxide and gold. AB - Planar lipid bilayers on solid supports mimic the fundamental structure of biological membranes and can be investigated using a wide range of surface sensitive techniques. Despite these advantages, planar bilayer fabrication is challenging, and there are no simple universal methods to form such bilayers on diverse material substrates. One of the novel methods recently proposed and proven to form a planar bilayer on silicon dioxide involves lipid deposition in organic solvent and solvent exchange to influence the phase of adsorbed lipids. To scrutinize the specifics of this solvent-assisted lipid bilayer (SALB) formation method and clarify the limits of its applicability, we have developed a simplified, continuous solvent-exchange version to form planar bilayers on silicon dioxide, gold, and alkanethiol-coated gold (in the latter case, a lipid monolayer is formed to yield a hybrid bilayer) and varied the type of organic solvent and rate of solvent exchange. By tracking the SALB formation process with simultaneous quartz crystal microbalance-dissipation (QCM-D) and ellipsometry, it was determined that the acoustic, optical, and hydration masses along with the acoustic and optical thicknesses, measured at the end of the process, are comparable to those observed by employing conventional fabrication methods (e.g., vesicle fusion). As shown by QCM-D measurements, the obtained planar bilayers are highly resistant to protein adsorption, and several, but not all, water-miscible organic solvents could be successfully used in the SALB procedure, with isopropanol yielding particularly high-quality bilayers. In addition, fluorescence recovery after photobleaching (FRAP) measurements demonstrated that the coefficient of lateral lipid diffusion in the fabricated bilayers corresponds to that measured earlier in the planar bilayers formed by vesicle fusion. With increasing rate of solvent exchange, it was also observed that the bilayer became incomplete and a phenomenological model was developed in order to explain this feature. The results obtained allowed us to clarify and discriminate likely steps of the SALB formation process as well as determine the corresponding influence of organic solvent type and flow conditions on these steps. Taken together, the findings demonstrate that the SALB formation method can be adapted to a continuous solvent-exchange procedure that is technically minimal, quick, and efficient to form planar bilayers on solid supports. PMID- 25111255 TI - Immunomodulatory agents for the treatment of cachexia. AB - PURPOSE OF REVIEW: In patients with advanced cancer, AIDS and end-stage organ diseases, symptoms of cachexia syndrome include decrease in appetite, weight loss, decreased performance status, and an increase in the systemic inflammatory response. Inflammatory cytokines and other immune interactions affect the lean tissue mass and body fat. It is hopeful that modulation of these inflammatory interactions may contribute to the delay in the development and treatment of cachexia. This review summarizes the current state of the art. RECENT FINDINGS: This article covers the role of inflammatory response in cachexia, measurement of inflammatory response, mechanism and measurement of cachexia, immunomodulation in cancer, drugs targeting inflammatory cytokines, effect of exercise in cachexia, and treatment of cancer cachexia using immunomodulatory agents. SUMMARY: Understanding the immune response associated with cachexia may improve future pharmacological modification of the cytokines. In addition, the multifactorial contributions to the mechanisms of cachexia indicate that a multimodal approach may be necessary to treat cachexia and its associated symptoms. PMID- 25111256 TI - Chronobiology of chronic pain: focus on diurnal rhythmicity of neuropathic pain. AB - PURPOSE OF REVIEW: Although circadian rhythmicity has long been recognized in various nociceptive pain conditions such as arthritis, diurnal pain patterns in neuropathic conditions have only recently been described. The purpose of this article is to review emerging evidence and discuss future research to further understand this phenomenon. RECENT FINDINGS: Secondary analyses of neuropathic pain clinical trials demonstrate that pain intensity fluctuations exhibit a distinct diurnal pattern that contrasts that of nociceptive pain conditions. Ongoing preclinical investigations support the phenomenon of circadian pain fluctuations and provide the opportunity to better describe pain chronobiology and to elucidate underlying mechanisms of circadian pain rhythmicity. SUMMARY: The observation of clinically relevant diurnal pain variability in neuropathic conditions has important implications for future research and treatment of pain. This is an immature research field, and further investigation is needed to better characterize these patterns in more detail, investigate contributory mechanisms, and to develop therapeutic strategies that exploit this phenomenon. PMID- 25111257 TI - A behavioral study of healthy and cancer genes by modeling electrical network. AB - In recent years, gene network modeling is gaining popularity in genomics to monitor the activity profile of genes. More specifically, the objective of the network modeling concept is to study the genetic behavior associated with disease. Previous researchers have designed network model at nucleotide level which produces more complexity for designing circuits mostly in case of gene expression studies. Whereas the authors have designed the present network model, based on amino acid level which is simpler as well as more appropriate for prediction of the genetic abnormality. In the present concept, SISO continuous and discrete system models of genes are realized using Foster network. The model is designed based on hydropathy index value of amino acids to study the biological system behavior. The time and phase response in continuous (s) domain and pole-zero distribution in discrete (z) domain are used as measurement metric in the present study. The simulated responses of the system show genetic instability for cancer genes which truly reflects the medical reports. The proposed modeling concept can be used, to accurately identify or separate out the diseased genes from healthy genes. PMID- 25111258 TI - Dihaloimidazolidinediones as versatile halodehydrating agents. AB - Dihaloimidazolidinediones containing geminal dibromides, dichlorides, or diiodides were synthesized and used to transform various alcohols to their corresponding alkyl halides in high yields and under mild conditions. High functional group tolerance and, in many cases, high selectivities were observed. Efforts toward elucidating the mechanism revealed that significant charge build up may occur at the eventual halogen containing carbon nucleus prior to substitution. PMID- 25111259 TI - A new class of organocatalysts: sulfenate anions. AB - Sulfenate anions are known to act as highly reactive species in the organic arena. Now they premiere as organocatalysts. Proof of concept is offered by the sulfoxide/sulfenate-catalyzed (1-10 mol%) coupling of benzyl halides in the presence of base to generate trans-stilbenes in good to excellent yields (up to 99%). Mechanistic studies support the intermediacy of sulfenate anions, and the deprotonated sulfoxide was determined to be the resting state of the catalyst. PMID- 25111266 TI - Computational studies support the role of the C7-sibirosamine sugar of the pyrrolobenzodiazepine (PBD) sibiromycin in transcription factor inhibition. AB - The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a group of sequence-selective, DNA minor-groove binding agents that covalently attach to guanine residues. Originally derived from Streptomyces species, a number of naturally occurring PBD monomers exist with varying A-Ring and C2-substituents. One such agent, sibiromycin, is unusual in having a glycosyl residue (sibirosamine) at its A-Ring C7-position. It is the most cytotoxic member of the naturally occurring PBD family and has the highest DNA-binding affinity. Recently, the analogue 9 deoxysibiromyin was produced biosynthetically by Yonemoto and co-workers.1 Differing only in the loss of the A-Ring C9-hydroxyl group, it was reported to have a significantly higher DNA-binding affinity than sibiromycin based on DNA thermal denaturation studies, although these data have since been retracted.2 As deletion of the C9-OH moiety, which points toward the DNA minor groove floor, might intuitively be expected to reduce DNA-binding affinity through the loss of hydrogen bonding, we carried out molecular dynamics simulations on the interaction of both molecules with DNA over a 10 ns time-course in explicit solvent. Our results suggest that the two molecules may differ in their sequence selectivity and that 9-deoxysibiromycin should have a lower binding affinity for certain sequences of DNA compared to sibiromycin. Our molecular dynamics results indicate that the C7-sibirosamine sugar does not form hydrogen bonding interactions with groups in the DNA minor-groove wall as previously reported, but instead points orthogonally out from the minor groove where it may inhibit the approach of DNA control proteins such as transcription factors. This was confirmed through a docking study involving sibiromycin and the GAL4 transcription factor, and these results could explain the significantly enhanced cytotoxicity of sibiromycin compared to other PBD family members without bulky C7 substituents. PMID- 25111267 TI - Chiral multidentate oxazoline ligands based on cyclophosphazene cores: synthesis, characterization and complexation studies. AB - Chiral oxazoline based bi and hexadentate ligands built on cyclophosphazene cores have been synthesized and characterized. (NPPh2)2[NP(m-OC6H4C(O)OCH3)2] (1) was prepared by the reaction of gem-(NPPh2)2(NPCl2) with methyl-3-hydroxy benzoate in the presence of Cs2CO3. Compound 1 was converted to the dicarboxylic acid (NPPh2)2[NP(m-OC6H4C(O)OH)2] (2) by base promoted hydrolysis with KO(t-Bu). The dicarboxylic acid 2 on reaction with oxalyl chloride followed by (S)-(+)-2-amino 3-methyl-1-butanol, triethylamine and mesyl chloride was converted to the C2 symmetric phosphazene based chiral bisoxazoline ligand (NPPh2)2[NP{m-OC6H4(4-iPr 2-Ox)}2] (3) (Ox = oxazolinyl). A similar C2-symmetric bisoxazoline derivative having an oxazoline group attached to the para position of the phenyl ring was also synthesized starting from (NPPh2)2[NP(p-OC6H4C(O)OCH3)2] (4) which was first converted to the dicarboxylic acid (NPPh2)2[NP(p-OC6H4C(O)OH)2] (5) and finally to (NPPh2)2[NP{p-OC6H4(4-iPr-2-Ox)}2] (6) and (NPPh2)2[NP{p-OC6H4(4-Ph-2-Ox)}2] (7) under similar reaction conditions. Reaction of 6 with Pd(OAc)2 in acetic acid at room temperature and with PdCl2(C6H5CN)2 in refluxing benzene resulted in chiral palladium complexes Pd(OAc)2(NPPh2)2[NP{p-OC6H4(4-iPr-2-Ox)}2] (8) and PdCl2(NPPh2)2[NP{p-OC6H4(4-iPr-2-Ox)}2] (9), respectively. The utility of these palladium complexes as chiral catalysts for the asymmetric rearrangement of trichloroacetimidates to trichloroacetamides has been explored. The hexa(methylbenzoate) derivative of cyclophosphazene [PN(OC6H4COOCH3)2]3 (10) on treatment with KO(t-Bu) and H2O gave the hexacarboxylic acid derivative [PN(OC6H4COOH)2]3 (11), which on treatment with oxalyl chloride followed by (S) (+)-2-amino-3-methyl-1-butanol/(S)-(+)-2-phenylglycinol, triethylamine and mesyl chloride was converted to the C3-symmetric cyclophosphazene based chiral hexaoxazoline ligands [PN{OC6H4(4-iPr-2-Ox)}2]3 (12) and [PN{OC6H4(4-Ph-2-Ox)}2]3 (13). The bis(phebox) derivative of the cyclophosphazene was prepared starting from (NPPh2)2[NP{OC6H3(COOCH3)2}2] (14), by the reaction of gem-Ph4P3N3Cl2 with dimethyl 5-hydroxyisophthalate in the presence of Cs2CO3. Compound 14 was converted to the tetracarboxylic acid (NPPh2)2[NP{OC6H3(COOH)2}2] (15) by base promoted hydrolysis with KO(t-Bu). The tetracarboxylic acid 15 on reaction with oxalyl chloride followed by (S)-(+)-2-amino-3-methyl-1-butanol/(S)-(+)-2 phenylglycinol, triethylamine and mesyl chloride was converted to the bis(phebox) substituted tetraphenylcyclophosphazene derivatives (NPPh2)2[NP{OC6H3(4-iPr-2 Ox)2}2] (16)/(NPPh2)2[NP{OC6H3(4-Ph-2-Ox)2}2] (17). A similar tetra(phebox) derivative was synthesized from (NPPh2)[NP{OC6H3(COOCH3)2}2]2 (18) which was first converted to (NPPh2)[NP{OC6H3(COOH)2}2]2 (19) and further converted to the tetra(phebox) derivative (NPPh2) [NP{OC6H3(4-Ph-2-Ox)2}2]2 (20). All new compounds were characterized by IR, NMR [(1)H, (13)C{(1)H} and (31)P{(1)H}] and HRMS studies. Compounds 1, 2, 4, 5, 7, 14 and 18 have also been structurally characterized. PMID- 25111268 TI - Optical properties of 4-bromobenzaldehyde derivatives in chloroform solution. AB - In this work we give a deeper insight into the electronic structure of a series of purely organic molecules that were recently employed as building blocks in crystals with very efficient phosphorescent emission. With this purpose, the low lying excited states of a series of 4-bromobenzaldehyde derivatives in chloroform solution are explored by means of time-dependent density functional theory (TDDFT) calculations, together with the absorption, fluorescence, and phosphorescence experimental spectra. The optical properties of the studied molecular models are extensively discussed, in terms of the frontier molecular orbitals involved in the relevant electronic transitions, the recorded and simulated absorption profiles, and the molecular geometries and transition energies of the emitting states. The calculations eventually help in the assignment of the character of the lowest lying singlet and triplet emitting states for these compounds. PMID- 25111269 TI - New media in pediatric surgery: innovations that have changed the way we educate and communicate. PMID- 25111270 TI - Comparative Analysis of Modified Laparoscopic Swenson and Laparoscopic Soave Procedure for Short-Segment Hirschsprung Disease in Children. AB - INTRODUCTION: This clinical analysis compared the characteristics and outcomes of modified laparoscopic Swenson (MLSw) and laparoscopic Soave (LS) procedures for short-segment Hirschsprung disease (HD) in children. PATIENTS AND METHODS: This clinical analysis involved a retrospective series of 42 pediatric patients with HD who underwent surgery from March 2007 to July 2012. Patients were divided into two groups: the LS group (n = 15) and the MLSw group (n = 27). Preoperative, operative, and postoperative data were collected, through patient follow-up periods ranging from 12 to 48 months, to compare perioperative/operative characteristics, postoperative complications, and outcomes between the two groups. Major measurements were analyzed statistically. RESULTS: On average, the patients in the LS group had a longer operating time (mean +/- standard deviation, 199 +/- 60 minutes) than those in the MLSw group (148 +/- 23 minutes) (p < 0.05). Blood loss was significantly less in the MLSw group (10 +/- 7 mL) than in the LS group (26 +/- 14 mL) (p < 0.05). There was no difference in feeding time between the two groups (p > 0.05). The MLSw group was discharged after a shorter hospitalization time (8 +/- 2 days) than the LS group (12 +/- 4 days) (p < 0.05). The MLSw group had lower incidences of soiling (5, 18.5% vs. 7, 46.7%) and constipation (1, 3.7% vs. 3, 20%) than the LS group in the early postoperative period, but no difference was found between the two groups in the rate of complications during the late postoperative period. CONCLUSIONS: The MLSw procedure did not increase the risk of injury to vital intrapelvic structures or the incidence of complications in surgery for short-segment HD. The early postoperative outcome was much better in the MLSw group than in the LS group, but long-term outcomes were similar. However, the MLSw procedure was simpler, resulting in reduced operating time and less intraoperative blood loss. PMID- 25111271 TI - Highly Efficient Conservative Treatment of Pectus Carinatum in Compliant Patients. AB - PURPOSE: Pectus carinatum is a thoracic deformity, which causes severe psychological problems for affected patients but almost no physical limitations. Invasive procedures are difficult to justify for this reason. We present a conservative therapy which leads to complete resolution in most cases when performed properly. METHODS: Between January 2008 and December 2012, 69 patients from 4 to 17 years with pectus carinatum were treated with a custom-fitted brace. Patients were stratified in children, adolescents, and adults. RESULTS: Mean therapy time was 7 months. Mean time of daily brace wearing was 12 to 15 hours. The results were evaluated by pictures taken before and after the therapy and from a patient interview. Standardized lateral views revealed a mean correction angle of 10 degrees in the children's group and 5 degrees in the adolescent group. In the adolescent group, 82% of patients judged the result as "excellent" or "good." In this large group with 56 patients, those who reported the result "unchanged" had a mean daily brace wearing time of 8.73 hours, those who judged the result as "good" 14.53 hours, and those who judged the result as "excellent" 18.36 hours. CONCLUSION: Our results show that pectus carinatum is efficiently treated with a customized brace therapy within 7 to 12 months. Best correction can be achieved in children and young adolescents. Daily brace-wearing time should be above 14 hours, ideally 24 hours. Duration of the treatment should be around 1 year. Treatment results correlate directly with the cooperation of the patients. PMID- 25111272 TI - Maximizing lymph node retrieval during surgical resection of Wilms tumor. AB - INTRODUCTION: Sampling lymph nodes (LNs) is independently associated with decreased recurrence and improved survival for Wilms tumor (WT). Despite sampling, we noted cases where a few or no LNs were identified after resection of WT. We hypothesized fewer LNs were identified when submitted en bloc with the tumor, compared with when submitted separately. PATIENTS/MATERIALS AND METHODS: We conducted a retrospective chart review from 2003 to 2012 of WT resection cases, examining the type of LN dissection, the specimens submitted to pathology, number of LNs evaluated, and complications associated with the procedure. RESULTS: We identified 74 children with WT; 59 of 74 (79.7%) had unilateral disease and 15 of 74 (20.3%) had bilateral disease. With unilateral disease, more LNs were identified by separate versus en bloc sampling (5.2 +/- 0.6 vs. 4.4 +/- 1.2 nodes, p=0.61). Both the methods identified fewer LNs compared with en bloc+separate sampling (12.5 +/- 2.7 nodes, p<0.001 and p=0.04, respectively). The majority of children with bilateral disease (10/15, 66.6%) did not have LN sampling intraoperatively. When submitted separately, 83.3 +/- 3.8% of all LNs were identified in the separate specimen, and two en bloc specimens that were noted to have adenopathy intraoperatively had no LNs pathologically identified. Few cases had complications, which did not appear associated with LN sampling. CONCLUSIONS: En bloc+separate sampling yields the most LNs during resection of WT. We recommend using this technique to facilitate the maximum number of LNs evaluated in WT. Low rates of LN sampling in bilateral disease may indicate decreased regard for sampling when tumor stage is already known. PMID- 25111273 TI - Lysyl oxidase expression is decreased in the developing diaphragm and lungs of nitrofen-induced congenital diaphragmatic hernia. AB - INTRODUCTION: Malformation of the nonmuscular tissue components in congenital diaphragmatic hernia (CDH) is thought to underlie the diaphragmatic defect, causing intrathoracic herniation of abdominal viscera and thus disturbing normal lung development. It has been shown that diaphragmatic and pulmonary morphogeneses require the structural integrity of connective tissue, and developmental mutations that inhibit the formation of extracellular matrix (ECM) result in CDH with hypoplastic lungs. Lysyl oxidase (lox), an extracellular enzyme that catalyzes the cross-linking of ECM proteins, plays an essential role during diaphragmatic and pulmonary development by controlling the formation of connective tissue. Furthermore, lox (-/-) knockouts exhibit abnormal connective tissue with diaphragmatic defects and impaired airway morphogenesis. We designed this study to investigate the hypothesis that diaphragmatic and pulmonary lox expression is decreased in the nitrofen-induced CDH model. MATERIALS AND METHODS: Timed-pregnant Sprague-Dawley rats were exposed to either nitrofen or vehicle on gestational day 9 (D9), and fetuses were harvested on selected time points D15 and D18. The micro-dissected fetal diaphragms (n=48) and lungs (n=48) were divided into two groups: control and nitrofen-exposed samples (n=12 per specimen and time point, respectively). Diaphragmatic and pulmonary gene expression levels of lox were analyzed by quantitative real-time polymerase chain reaction. Immunohistochemical staining was performed to evaluate lox protein expression in diaphragms and lungs. RESULTS: Relative mRNA expression of lox was significantly reduced in diaphragms and lungs of nitrofen-exposed fetuses on D15 (0.29 +/- 0.08 vs. 0.12 +/- 0.05; p<0.05 and 0.52 +/- 0.44 vs. 0.20 +/- 0.04; p<0.05) and D18 (0.90 +/- 0.25 vs. 0.57 +/- 0.23; p<0.05 and 0.59 +/- 0.26 vs. 0.35 +/- 0.09; p<0.05) compared with controls. Diaphragmatic and pulmonary immunoreactivity of lox was markedly decreased in nitrofen-exposed fetuses on D15 and D18 compared with controls. CONCLUSIONS: Decreased lox expression during diaphragmatic development and lung branching morphogenesis may interfere with normal cross linking of ECM proteins, disrupting the integrity of connective tissue, and contributing to the diaphragmatic defect and impaired airway formation in the nitrofen-induced CDH model. PMID- 25111274 TI - Tumor-associated energy homeostasis: hepatoblastoma and neuroblastoma affect glucose and lipid metabolism as well as ghrelin, GLP-1, and PYY in nude rats. AB - INTRODUCTION: The "metabolic competition" for nutrients between cancer cells and the patient has emerged as an important research area. For pediatric oncology, it remains unclear whether the neuroendokrine regulation of appetite by gastrointestinal hormones such as ghrelin "eat", GLP-1 (glucagon-like peptide, "do not eat"), and PYY (peptide tyrosine-tyrosine, "do not eat") is influenced by tumor growth. MATERIAL AND METHODS: In a prospective randomized study, human hepatoblastoma (HB) and neuroblastoma (NB) cells (3 * 10(6)) were transplanted into the abdominal wall of immune-incompetent (nu/nu) rats (ethic committee approval: TVV43/11). Sham-operated animals received cell culture medium only. Tumor growth was allowed for 8 weeks. Then, all the animals underwent a 2-hour oGTT (oral glucose tolerance test) and were assessed for serum levels of glucose, insulin, ghrelin, GLP-1, and PYY. Finally, all tumor masses and adipose tissues were excised and calculated. RESULTS: Total body weight (including tumor masses) differed for HB (329+31 g), but not for NB (358+22 g) compared with Sham (361+35 g). Subcutaneous adipose tissue was significantly decreased for both the tumor groups (HB=2.6 g, NB=2.1 g, and Sham=3.5 g). Only for NB, fasting glucose (3.4 + 0.6 mmol/L) and insulin (0.89+0.11 ng/mL) levels were significantly decreased compared with Sham (4.4+0.6 mmol/L; 1.19+0.36 ng/mL) only. During the oGTT (all data calculated as area under the curve, AUC) glucose levels were significantly increased for HB (104 +/- 10) and NB (102 +/- 13) compared with Sham (84 +/- 3), but insulin levels remained similar for either group. Triglyceride levels were increased for HB (0.51 mmol/L) and especially NB (0.73 mmol/L) compared with Sham (0.34 mmol/L). Inflammatory parameters did not differ between the groups. Total ghrelin levels were significantly increased for NB (111 +/- 10) and altered for HB (102 +/- 15) compared with Sham (84 +/- 8). Vice versa GLP-1 was statistically decreased in HB (92 +/- 7) and NB (88 +/- 12) compared with Sham (127 +/- 13). Finally, PYY levels were nonsignificantly reduced for HB (117 +/- 5) and NB (120 +/- 4) compared with Sham (146 +/- 12). PMID- 25111275 TI - Perioperative management after high-dose chemotherapy with autologous or allogeneic hematopoietic stem cell transplantation for pediatric solid tumors. AB - INTRODUCTION: An increasing number of children with advanced malignancies have recently received high-dose chemotherapy (HDC) with hematopoietic stem cell transplantation (HSCT), followed by surgery. In this study, we reviewed our experience with surgery after HDC and autologous (auto) or allogeneic (allo) HSCT to elucidate the problems associated with this treatment and establish the optimum surgical management strategy. PATIENTS AND METHODS: We retrospectively reviewed the cases of 24 children with advanced malignancy treated with HDC and HSCT before tumor resection at our institution. The tumors included 18 neuroblastomas, 5 soft tissue sarcomas, 2 hepatoblastomas, and 1 Wilms tumor. The source of hematopoietic stem cells was auto-HSCT in 19 patients and allo-HSCT in 5 patients. To be able to undergo surgery, it was necessary that the patient's general condition, including hemostasis, should be fairly good and that the results of hematological examinations should include a white blood cell (WBC) count of>1,000/uL, hemoglobin level of>10 g/dL and platelet count of>5 * 10(4)/uL. RESULTS: The mean duration before WBC recovery after HSCT was 14.5 +/- 1.4 days after auto-HSCT and 23.8 +/- 1.2 days after allo-HSCT, respectively (p<0.01). The mean duration before platelet recovery after HSCT was 46.5 +/- 5.2 days for auto-HSCT and 48.6 +/- 5.5 days for allo-HSCT (not significant [n.s.]). The mean interval between allo-HSCT and surgery was significantly longer (92.8 +/ 6.2 days) than that between auto-HSCT and surgery (57.0 +/- 3.9 days) (p<0.01), likely because of the use of steroids and immunosuppressants after HSCT. The tumors were completely resected in all cases without severe complications. All the patients treated with allo-HSCT had an acute graft versus host (aGVH) reaction at 2 to 3 weeks after HSCT, and specifically required the administration of steroids and immunosuppressants to prevent aGVH. The postoperative complications included paralytic ileus in two cases and a tacrolimus-associated encephalopathy in one case involving allo-HSCT. In half of the patients, the WBC count was not elevated after surgery, whereas the postoperative serum C-reactive protein (CRP) level was elevated in all cases. CONCLUSIONS: Our data indicate that surgical treatment can be safely performed even after HDC with HSCT if attention is paid to myelosuppression and the adverse effects of both chemotherapeutic agents and immunosuppressants. PMID- 25111276 TI - Nursing Intervention for Outpatient Rehabilitation in Pediatric Patients with Hirschsprung Disease after Colectomy. AB - OBJECTIVE: The present study was designed to evaluate the effectiveness of a nursing intervention program for outpatient rehabilitation of children with Hirschsprung-associated enterocolitis (HAEC) after radical colectomy for Hirschsprung disease (HD). BACKGROUND: Postoperative outcomes severely affect the quality of life in pediatric HD patients after operation. The improvement in defecation function is regarded as one of the most useful parameters to evaluate the quality of life in HD patients after radical intestinal resection. A close attention should also be paid to the patients' ability of social adaptation. METHODS: This prospective, randomized control trial enrolled 85 pediatric patients with HAEC after colectomy. They were randomly divided into the control and intervention groups. All the patients were followed up for 6 to 12 months after initial HAEC treatment. RESULTS: The intervention group had a lower enterocolitis recurrence rate than the control group, with a better ability to control defecation and their parents had better rehabilitation nursing knowledge (p < 0.05). The degree of parents' satisfaction regarding the outcome was significantly better in the intervention group than that in the control group (p < 0.05). CONCLUSION: A systemic rehabilitation nursing program could decrease enterocolitis recurrence, improve the recovery of anorectal functions, and enhance the quality of life in the pediatric patients after radical colectomy. PMID- 25111277 TI - What is "telemedicine" and what does it mean for a pediatric surgeon? AB - Telemedicine is a broad term and has recently become a household term in the medical field. However, there are many interpretations as to what the term "telemedicine" means. There are many facets to telemedicine and here we describe all of the elements of telemedicine, a glossary of terms, and how they relate to pediatric surgery. PMID- 25111278 TI - Telementoring: the surgical tool of the future. AB - With decreased resident experience during training and the constant evolution of new surgical techniques, surgeons are at risk for complications during the early part of the learning curve. Mentorship by experienced surgeons may mitigate these complications. The availability of such advanced telepresence technology makes it logical that this will be used as part of the model to proctor, mentor, and train practicing surgeons. Here, we review the current state of telementoring. PMID- 25111279 TI - Online resources in pediatric surgery: the new era of medical information. AB - Tele-education has the potential to facilitate rapid sharing and dissemination of current research and knowledge among pediatric surgeons around the world. Classically, the exchange of surgical research occurred via national surgical conferences, articles published in peer-reviewed journals, and textbooks. The advent of Web 2.0 and the rapid pace of technologic advancement have allowed knowledge, education, and research to be exchanged online. Virtual symposiums act as online conferences where participants present and debate new research and surgical techniques in real-time web meetings. Resource libraries allow up-to date information to be archived and viewed at the user's convenience, bypassing the need to wait long periods for paper publications. Tele-education allows pediatric surgeons to connect and share ideas around the world, while saving time and money. PMID- 25111280 TI - How pediatric surgeons use social media to attract new patients. AB - Social media has changed the landscape of online interaction for all doctors including pediatric surgeons. Of course the public including our patients and potential new patients having immediate access to these sites through mobile devices and iPads has contributed immensely to this phenomenon. Nonetheless, it seems that we are all rushing to get in front of our target audience and to engage in a relationship with them in a cost-effective fashion. This article will discuss the role of the Internet and media and how you can use this technology to attract new pediatric patients to your practice. PMID- 25111282 TI - Delirium and hypovitaminosis D: neuroimaging findings. AB - The authors examined the frequency of neuroimaging findings of cortical atrophy and/or cerebrovascular disease in patients with delirium with hypovitaminosis D and normal vitamin D levels. Of 32 patients with delirium with hypovitaminosis D who were neuroimaged, 91.4% had neuroimaging findings, despite only five cases having a comorbid diagnosis of dementia. Similar frequencies of cortical atrophy and/or cerebrovascular disease were found in patients with delirium with normal vitamin D levels. Further research with a larger sample size is needed to compare neuroimaging findings between normal patients and patients with hypovitaminosis D with delirium. PMID- 25111281 TI - Osteoblast maturation on microtextured titanium involves paracrine regulation of bone morphogenetic protein signaling. AB - Osteoblasts are sensitive to surface microtopography and chemistry. Osteoblast differentiation and maturation are higher in vitro and bone formation and osseointegration enhanced in vivo on microstructured titanium (Ti) compared to smooth surfaces. Cells increased BMP2 expression on microtextured Ti alloy, suggesting a paracrine role in regulating osteoblast maturation. However, recent studies show that exogenous BMP2 inhibits osteoblast production of anti inflammatory cytokines and osteocalcin, indicating that control of BMP-signaling may be involved. This study examined whether cells modulate BMP ligands, receptors, and inhibitors during osteoblast maturation on Ti, specifically focusing on the roles of BMP2 and Noggin (NOG). mRNA and protein for BMP2, BMP4, and BMP7 and receptors BMPR1A, BMPR1B, and BMPR2, and BMP inhibitors were upregulated on microtextured surfaces in comparison to smooth surfaces. Maturation on microstructured Ti was slightly enhanced with exogenous BMP2 while NOG addition inhibited osteoblast maturation. Cells with NOG knocked down significantly increased osteoblast maturation. These results demonstrate that BMP related molecules are controlled during osteoblast maturation on microstructured Ti surfaces and that endogenous NOG is an important regulator of the process. Modifying paracrine BMP signaling may yield more robust bone formation than application of exogenous BMPs. PMID- 25111284 TI - Editorial. PMID- 25111283 TI - Hybrid elastin-like polypeptide-polyethylene glycol (ELP-PEG) hydrogels with improved transparency and independent control of matrix mechanics and cell ligand density. AB - Hydrogels have been developed as extracellular matrix (ECM) mimics both for therapeutic applications and basic biological studies. In particular, elastin like polypeptide (ELP) hydrogels, which can be tuned to mimic several biochemical and physical characteristics of native ECM, have been constructed to encapsulate various types of cells to create in vitro mimics of in vivo tissues. However, ELP hydrogels become opaque at body temperature because of ELP's lower critical solution temperature behavior. This opacity obstructs light-based observation of the morphology and behavior of encapsulated cells. In order to improve the transparency of ELP hydrogels for better imaging, we have designed a hybrid ELP polyethylene glycol (PEG) hydrogel system that rapidly cross-links with tris(hydroxymethyl) phosphine (THP) in aqueous solution via Mannich-type condensation. As expected, addition of the hydrophilic PEG component significantly improves the light transmittance. Coherent anti-Stokes Raman scattering (CARS) microscopy reveals that the hybrid ELP-PEG hydrogels have smaller hydrophobic ELP aggregates at 37 degrees C. Importantly, this hydrogel platform enables independent tuning of adhesion ligand density and matrix stiffness, which is desirable for studies of cell-matrix interactions. Human fibroblasts encapsulated in these hydrogels show high viability (>98%) after 7 days of culture. High-resolution confocal microscopy of encapsulated fibroblasts reveals that the cells adopt a more spread morphology in response to higher RGD ligand concentrations and softer gel mechanics. PMID- 25111285 TI - Psychometric properties of the Geriatric Anxiety Inventory (GAI) and its short form (GAI-SF) in a clinical and non-clinical sample of older adults. AB - BACKGROUND: The Geriatric Anxiety Inventory is a 20-item geriatric-specific measure of anxiety severity. While studies suggest good internal consistency and convergent validity, divergent validity from measures of depression are weak. Clinical cutoffs have been developed that vary across studies due to the small clinical samples used. A six-item short form (GAI-SF) has been developed, and while this scale is promising, the research assessing the psychometrics of this scale is limited. METHODS: This study examined the psychometric properties of GAI and GAI-SF in a large sample of 197 clinical geriatric participants with a comorbid anxiety and unipolar mood disorder, and a non-clinical control sample (N = 59). RESULTS: The internal consistency and convergent validity with other measures of anxiety was adequate for GAI and GAI-SF. Divergent validity from depressive symptoms was good in the clinical sample but weak in the total and non clinical samples. Divergent validity from cognitive functioning was good in all samples. The one-factor structure was replicated for both measures. Receiver Operating Characteristic analyses indicated that the GAI is more accurate at identifying clinical status than the GAI-SF, although the sensitivity and specificity for the recommended cutoffs was adequate for both measures. CONCLUSIONS: Both GAI and GAI-SF show good psychometric properties for identifying geriatric anxiety. The GAI-SF may be a useful alternative screening measure for identifying anxiety in older adults. PMID- 25111286 TI - Prevalence of HPV and variation of HPV 16/HPV 18 E6/E7 genes in cervical cancer in women in South West China. AB - Genetic variations of High-Risk HPV E6/E7 may be associated with the development of cervical cancer in specific geographic regions. Few data have been reported about the HPV prevalence and E6/E7 variants among cervical cancer patients in Southwest China. This study was designed to investigate the prevalence of HPV and E6/E7 variants of most prevalent HPV among cervical cancer patients in Southwest China. After genotyping, E6/E7 genes of most prevalent HR HPV samples were sequenced and analyzed. Phylogenetic trees were then constructed, followed by an analysis of the diversity of secondary structure and selection pressures. HPV 16 (73.8%) and HPV 18 (16.4%) are the most prevalent infection types among cervical cancer patients, followed by HPV 58, HPV 56 and HPV 59, which is different from the high HPV 58 infection rate of outpatients in this region. Eighteen single nucleotide changes were observed in HPV 16 E6 with 13/18 non-synonymous mutations (5 in beta sheet and 2 in alpha helix). Ten single nucleotide changes were identified among HPV 16 E7 with 3/10 non-synonymous mutations. Three single nucleotide changes were observed in HPV 18 E6 with one non-synonymous mutation, and only one synonymous mutation was identified in HPV 18 E7. HPV 16 E6-D25E, E7 N29S and E7-T846C (S95S) exhibited a prevalent linkage mutation. The phylogenetic tree demonstrates that European and Asian lineages were the main patterns. This study may help understand the intrinsic geographical relatedness and oncogenic potential of HR HPV and contributes further to research of diagnostic, therapeutic and therapeutic vaccine strategy. PMID- 25111289 TI - Global carbon benefits of material substitution in passenger cars until 2050 and the impact on the steel and aluminum industries. AB - Light-weighting of passenger cars using high-strength steel or aluminum is a common emissions mitigation strategy. We provide a first estimate of the global impact of light-weighting by material substitution on GHG emissions from passenger cars and the steel and aluminum industries until 2050. We develop a dynamic stock model of the global car fleet and combine it with a dynamic MFA of the associated steel, aluminum, and energy supply industries. We propose four scenarios for substitution of conventional steel with high-strength steel and aluminum at different rates over the period 2010-2050. We show that light weighting of passenger cars can become a "gigaton solution": Between 2010 and 2050, persistent light-weighting of passenger cars can, under optimal conditions, lead to cumulative GHG emissions savings of 9-18 gigatons CO2-eq compared to development business-as-usual. Annual savings can be up to 1 gigaton per year. After 2030, enhanced material recycling can lead to further reductions: closed loop metal recycling in the automotive sector may reduce cumulative emissions by another 4-6 gigatons CO2-eq. The effectiveness of emissions mitigation by material substitution significantly depends on how the recycling system evolves. At present, policies focusing on tailpipe emissions and life cycle assessments of individual cars do not consider this important effect. PMID- 25111287 TI - Is there a role for base excision repair in estrogen/estrogen receptor-driven breast cancers? AB - Estrogen and estrogen metabolite-induced reactive oxygen species generation can promote oxidative DNA base damage. If unrepaired, base damaging lesions could accelerate mutagenesis, leading to a "mutator phenotype" characterized by aggressive behavior in estrogen-estrogen receptor (ER)-driven breast cancer. To test this hypothesis, we investigated 1406 ER(+) early-stage breast cancers with 20 years' long-term clinical follow-up data for DNA polymerase beta (pol beta), flap endonuclease 1 (FEN1), AP endonuclease 1 (APE1), X-ray cross-complementation group 1 protein (XRCC1), single-strand monofunctional uracil glycosylase-1 (SMUG1), poly (ADP-ribose) polymerase 1 (PARP1), ataxia telangiectasia mutated and Rad3 related (ATR), ataxia telangiectasia mutated (ATM), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Chk1, Chk2, p53, breast cancer susceptibility gene 1 (BRCA1), and topoisomerase 2 (TOPO2) expression. Multivariate Cox proportional hazards model was used to calculate a DNA repair prognostic index and correlated to clinicopathological variables and survival outcomes. Key base excision repair (BER) proteins, including XRCC1, APE1, SMUG1, and FEN1, were independently associated with poor breast cancer-specific survival (BCSS) (ps<=0.01). Multivariate Cox model stratified patients into four distinct prognostic sub-groups with worsening BCSS (ps<0.01). In addition, compared with prognostic sub-group 1, sub-groups 2, 3, and 4 manifest increasing tumor size, grade, mitosis, pleomorphism, differentiation, lymphovascular invasion, high Ki67, loss of Bcl-2, luminal B phenotype (ps<=0.01), and poor survival, including in patients who received tamoxifen adjuvant therapy (p<0.00001). Our observation supports the hypothesis that BER-directed stratification could inform appropriate therapies in estrogen-ER-driven breast cancers. Antioxid. PMID- 25111290 TI - Breaking down the reactivity of lambda(3)-iodanes: the impact of structure and bonding on competing reaction mechanisms. AB - The functionalization of arenes via diaryliodonium salts has gained considerable attention in synthesis, as these compounds react under mild conditions. Mechanistic studies have shown that the formation of corresponding lambda(3) iodane intermediates takes a key role, as they determine the course and selectivity of the reaction. Bridged diaryliodonium salts, featuring a heterocyclic moiety involving the iodine atom, were shown to exhibit a distinctly different reactivity, leading to different products. These products are not just the result of reductive elimination reactions but may also arise via radical mechanisms. Our quantum chemical calculations reveal that the lambda(3)-iodane intermediate is also the "gateway" for reactions that are observed only for strained bridged systems. At the same time, we find a remarkable affinity of the hypervalent region to planarity for all reaction mechanisms. This also explains the correlation between the size of the bridge connecting the aryl groups and the reaction products observed. Furthermore, the energetics of these competing reactions are examined by analysis of the mechanisms. Finally, using model compounds, some of the basic features governing the reactivity of lambda(3) iodanes are discussed. PMID- 25111291 TI - Translational research in acute central nervous system injury: lessons learned and the future. AB - IMPORTANCE: Research to improve outcomes from acute central nervous system (CNS) injury has progressed little, although limited examples (eg, induced hypothermia for out-of-hospital ventricular fibrillation cardiac arrest and birth asphyxia and tissue plasminogen activator for ischemic stroke) have proved that it is possible to favorably alter outcome. OBJECTIVE: To chronicle the evolution of preclinical research designed to provide therapeutic interventions for acute CNS injury. EVIDENCE REVIEW: Preclinical literature cited by major clinical intervention trials was systematically assessed with respect to fulfillment of fundamental elements of experimental design in current guidelines. FINDINGS: Preclinical studies of acute CNS injury to date have a poor record of adhering to basic tenets of experimental design, including randomization, concealment of treatment allocation, definition of sustained robustness of therapeutic benefit, and emulation of clinical disease. Major clinical trials continue to be justified and conducted on the basis of weak preclinical evidence. Publication of preclinical research guidelines and endorsement by scientific journals have been insufficient to alter practice. Novel approaches to preclinical therapeutic development, including multicenter phase 3 trials and preclinical trial registries that document a priori experimental design and primary dependent variables, may overcome this intransigence and enhance possibility for therapeutic breakthroughs. CONCLUSIONS AND RELEVANCE: Current knowledge of acute CNS injury dictates that therapeutic discovery and translation apply known tenets of sound experimental design and emulation of the clinical disorder targeted for therapeutic intervention. Peer-review systems must demand these qualities in proposed and published research to assess validity and potential for clinical translation. PMID- 25111292 TI - Mental health and substance use among bisexual youth and non-youth in Ontario, Canada. AB - Research has shown that bisexuals have poorer health outcomes than heterosexuals, gays, or lesbians, particularly with regard to mental health and substance use. However, research on bisexuals is often hampered by issues in defining bisexuality, small sample sizes, and by the failure to address age differences between bisexuals and other groups or age gradients in mental health. The Risk & Resilience Survey of Bisexual Mental Health collected data on 405 bisexuals from Ontario, Canada, using respondent-driven sampling, a network-based sampling method for hidden populations. The weighted prevalence of severe depression (PHQ 9 >= 20) was 4.7%, possible anxiety disorder (OASIS >= 8) was 30.9%, possible post-traumatic stress disorder (PCL-C >= 50) was 10.8%, and past year suicide attempt was 1.9%. With respect to substance use, the weighted prevalence of problem drinking (AUDIT >= 5) was 31.2%, and the weighted prevalence of illicit polydrug use was 30.5%. Daily smoking was low in this sample, with a weighted prevalence of 7.9%. Youth (aged 16-24) reported significantly higher weighted mean scores on depression and post-traumatic stress disorder, and higher rates of past year suicidal ideation (29.7% vs. 15.2%) compared with those aged 25 and older. The burden of mental health and substance use among bisexuals in Ontario is high relative to population-based studies of other sexual orientation groups. Bisexual youth appear to be at risk for poor mental health. Additional research is needed to understand if and how minority stress explains this burden. PMID- 25111293 TI - Parental modelling of eating behaviours: observational validation of the Parental Modelling of Eating Behaviours scale (PARM). AB - Parents are important role models for their children's eating behaviours. This study aimed to further validate the recently developed Parental Modelling of Eating Behaviours Scale (PARM) by examining the relationships between maternal self-reports on the PARM with the modelling practices exhibited by these mothers during three family mealtime observations. Relationships between observed maternal modelling and maternal reports of children's eating behaviours were also explored. Seventeen mothers with children aged between 2 and 6 years were video recorded at home on three separate occasions whilst eating a meal with their child. Mothers also completed the PARM, the Children's Eating Behaviour Questionnaire and provided demographic information about themselves and their child. Findings provided validation for all three PARM subscales, which were positively associated with their observed counterparts on the observational coding scheme (PARM-O). The results also indicate that habituation to observations did not change the feeding behaviours displayed by mothers. In addition, observed maternal modelling was significantly related to children's food responsiveness (i.e., their interest in and desire for foods), enjoyment of food, and food fussiness. This study makes three important contributions to the literature. It provides construct validation for the PARM measure and provides further observational support for maternal modelling being related to lower levels of food fussiness and higher levels of food enjoyment in their children. These findings also suggest that maternal feeding behaviours remain consistent across repeated observations of family mealtimes, providing validation for previous research which has used single observations. PMID- 25111294 TI - Alternatives to the six-minute walk test in pulmonary arterial hypertension. AB - INTRODUCTION: The physiological response during the endurance shuttle walk test (ESWT), the cycle endurance test (CET) and the incremental shuttle walk test (ISWT) remains unknown in PAH. We tested the hypothesis that endurance tests induce a near-maximal physiological demand comparable to incremental tests. We also hypothesized that differences in respiratory response during exercise would be related to the characteristics of the exercise tests. METHODS: Within two weeks, twenty-one PAH patients (mean age: 54(15) years; mean pulmonary arterial pressure: 42(12) mmHg) completed two cycling exercise tests (incremental cardiopulmonary cycling exercise test (CPET) and CET) and three field tests (ISWT, ESWT and six-minute walk test (6MWT)). Physiological parameters were continuously monitored using the same portable telemetric device. RESULTS: Peak oxygen consumption (VO(2peak)) was similar amongst the five exercise tests (p = 0.90 by ANOVA). Walking distance correlated markedly with the VO(2peak) reached during field tests, especially when weight was taken into account. At 100% exercise, most physiological parameters were similar between incremental and endurance tests. However, the trends overtime differed. In the incremental tests, slopes for these parameters rose steadily over the entire duration of the tests, whereas in the endurance tests, slopes rose sharply from baseline to 25% of maximum exercise at which point they appeared far less steep until test end. Moreover, cycling exercise tests induced higher respiratory exchange ratio, ventilatory demand and enhanced leg fatigue measured subjectively and objectively. CONCLUSION: Endurance tests induce a maximal physiological demand in PAH. Differences in peak respiratory response during exercise are related to the modality (cycling vs. walking) rather than the progression (endurance vs. incremental) of the exercise tests. PMID- 25111295 TI - Biological construction of single-walled carbon nanotube electron transfer pathways in dye-sensitized solar cells. AB - We designed and mass-produced a versatile protein supramolecule that can be used to manufacture a highly efficient dye-sensitized solar cell (DSSC). Twelve single walled carbon-nanotube (SWNT)-binding and titanium-mineralizing peptides were genetically integrated on a cage-shaped dodecamer protein (CDT1). A process involving simple mixing of highly conductive SWNTs with CDT1 followed by TiO2 biomineralization produces a high surface-area/weight TiO2 -(anatase)-coated intact SWNT nanocomposite under environmentally friendly conditions. A DSSC with a TiO2 photoelectrode containing 0.2 wt % of the SWNT-TiO2 nanocomposite shows a current density improvement by 80% and a doubling of the photoelectric conversion efficiency. The SWNT-TiO2 nanocomposite transfers photon-generated electrons from dye molecules adsorbed on the TiO2 to the anode electrode swiftly. PMID- 25111297 TI - Novel method to characterize immune cells from human prostate tissue. AB - BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common benign adenoma and prostate cancer is the most frequent malignancy in men over 50 years of age in the Western world, where it remains a significant health problem. Prostate lesions are known to contain immune cells, which may contribute to the immune control of tumor progression. However, due to their low numbers and restricted access to necessary material it is difficult to isolate immune cells from prostate tissue to characterize their immunological features. METHODS: An efficient and robust method was developed to process prostate tissue and isolate immune cells for phenotypic analysis by multicolor flow cytometry as downstream application. Fresh prostate tissue from 11 patients undergoing surgery for bladder outlet obstruction due to BPH was processed to evaluate the number, viability, yield, and frequency of various immune cell types. RESULTS: The presented method does not include enzymatic digestion nor incubation steps at 37 degrees C, increasing cellular viability and avoiding possible phenotypic modification. Various immune cell populations were detected in all patient samples and the median cellular viability was 90%. The number of detected events of individual cell populations varied between patients. The median frequency of different immune cell populations also varied, being 87% for the CD3- and 15% for the CD3+ cell population. CONCLUSIONS: This novel method will allow the phenotypic characterization of immune cell populations present in tumor tissue of prostate cancer patients and promote development of novel approaches to immunotherapy of the disease. PMID- 25111296 TI - A new model for predicting non-sentinel lymph node status in Chinese sentinel lymph node positive breast cancer patients. AB - BACKGROUND: Our goal is to validate the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and Stanford Online Calculator (SOC) for predicting non-sentinel lymph node (NSLN) metastasis in Chinese patients, and develop a new model for better prediction of NSLN metastasis. METHODS: The MSKCC nomogram and SOC were used to calculate the probability of NSLN metastasis in 120 breast cancer patients. Univariate and multivariate analyses were performed to evaluate the relationship between NSLN metastasis and clinicopathologic factors, using the medical records of the first 80 breast cancer patients. A new model predicting NSLN metastasis was developed from the 80 patients. RESULTS: The MSKCC and SOC predicted NSLN metastasis in a series of 120 patients with an area under the receiver operating characteristic curve (AUC) of 0.688 and 0.734, respectively. For predicted probability cut-off points of 10%, the false-negative (FN) rates of MSKCC and SOC were both 4.4%, and the negative predictive value (NPV) 75.0% and 90.0%, respectively. Tumor size, Kiss-1 expression in positive SLN and size of SLN metastasis were independently associated with NSLN metastasis (p<0.05). A new model (Peking University People's Hospital, PKUPH) was developed using these three variables. The MSKCC, SOC and PKUPH predicted NSLN metastasis in the second 40 patients from the 120 patients with an AUC of 0.624, 0.679 and 0.795, respectively. CONCLUSION: MSKCC nomogram and SOC did not perform as well as their original researches in Chinese patients. As a new predictor, Kiss-1 expression in positive SLN correlated independently with NSLN metastasis strongly. PKUPH model achieved higher accuracy than MSKCC and SOC in predicting NSLN metastasis in Chinese patients. PMID- 25111298 TI - Impact of bottom trawling on deep-sea sediment properties along the flanks of a submarine canyon. AB - The offshore displacement of commercial bottom trawling has raised concerns about the impact of this destructive fishing practice on the deep seafloor, which is in general characterized by lower resilience than shallow water regions. This study focuses on the flanks of La Fonera (or Palamos) submarine canyon in the Northwestern Mediterranean, where an intensive bottom trawl fishery has been active during several decades in the 400-800 m depth range. To explore the degree of alteration of surface sediments (0-50 cm depth) caused by this industrial activity, fishing grounds and control (untrawled) sites were sampled along the canyon flanks with an interface multicorer. Sediment cores were analyzed to obtain vertical profiles of sediment grain-size, dry bulk density, organic carbon content and concentration of the radionuclide 210Pb. At control sites, surface sediments presented sedimentological characteristics typical of slope depositional systems, including a topmost unit of unconsolidated and bioturbated material overlying sediments progressively compacted with depth, with consistently high 210Pb inventories and exponential decaying profiles of 210Pb concentrations. Sediment accumulation rates at these untrawled sites ranged from 0.3 to 1.0 cm y-1. Sediment properties at most trawled sites departed from control sites and the sampled cores were characterized by denser sediments with lower 210Pb surface concentrations and inventories that indicate widespread erosion of recent sediments caused by trawling gears. Other alterations of the physical sediment properties, including thorough mixing or grain-size sorting, as well as organic carbon impoverishment, were also visible at trawled sites. This work contributes to the growing realization of the capacity of bottom trawling to alter the physical properties of surface sediments and affect the seafloor integrity over large spatial scales of the deep-sea. PMID- 25111299 TI - Biosynthetic pathway of the phytohormone auxin in insects and screening of its inhibitors. AB - Insect galls are abnormal plant tissues induced by galling insects. The galls are used for food and habitation, and the phytohormone auxin, produced by the insects, may be involved in their formation. We found that the silkworm, a non galling insect, also produces an active form of auxin, indole-3-acetic acid (IAA), by de novo synthesis from tryptophan (Trp). A detailed metabolic analysis of IAA using IAA synthetic enzymes from silkworms indicated an IAA biosynthetic pathway composed of a three-step conversion: Trp -> indole-3-acetaldoxime -> indole-3-acetaldehyde (IAAld) -> IAA, of which the first step is limiting IAA production. This pathway was shown to also operate in gall-inducing sawfly. Screening of a chemical library identified two compounds that showed strong inhibitory activities on the conversion step IAAld -> IAA. The inhibitors can be efficiently used to demonstrate the importance of insect-synthesized auxin in gall formation in the future. PMID- 25111301 TI - The psychology of coordination and common knowledge. AB - Research on human cooperation has concentrated on the puzzle of altruism, in which 1 actor incurs a cost to benefit another, and the psychology of reciprocity, which evolved to solve this problem. We examine the complementary puzzle of mutualism, in which actors can benefit each other simultaneously, and the psychology of coordination, which ensures such benefits. Coordination is facilitated by common knowledge: the recursive belief state in which A knows X, B knows X, A knows that B knows X, B knows that A knows X, ad infinitum. We test whether people are sensitive to common knowledge when deciding whether to engage in risky coordination. Participants decided between working alone for a certain profit and working together for a potentially higher profit that they would receive only if their partner made the same choice. Results showed that more participants attempted risky coordination when they and their prospective partner had common knowledge of the payoffs (broadcast over a loudspeaker) than when they had only shared knowledge (conveyed to both by a messenger) or private knowledge (revealed to each partner separately). These results support the hypothesis that people represent common knowledge as a distinct cognitive category that licenses them to coordinate with others for mutual gain. We discuss how this hypothesis can provide a unified explanation for diverse phenomena in human social life, including recursive mentalizing, performative speech acts, public protests, hypocrisy, and self-conscious emotional expressions. PMID- 25111300 TI - Mycobacterium Avium subsp. paratuberculosis isolates induce in vitro granuloma formation and show successful survival phenotype, common anti-inflammatory and antiapoptotic responses within ovine macrophages regardless of genotype or host of origin. AB - The analysis of the early macrophage responses, including bacterial growth within macrophages, represents a powerful tool to characterize the virulence of clinical isolates of Mycobcaterium avium susbp. paratuberculosis (Map). The present study represents the first assessment of the intracellular behaviour in ovine monocyte derived macrophages (MDMs) of Map isolates representing distinct genotypes (C, S and B), and isolated from cattle, sheep, goat, fallow deer, deer, and wild boar. Intracellular growth and survival of the selected isolates in ovine MDMs was assessed by quantification of CFUs inside of the host cells at 2 h p.i. (day 0) and 7 d p. i. using an automatic liquid culture system (Bactec MGIT 960). Variations in bacterial counts over 7 days from the baseline were small, in a range between 1.63 to 1.05-fold. After 7 d of infection, variations in the estimated log10 CFUs between all the tested isolates were not statistically significant. In addition, ovine MDMs exhibited enhanced anti-inflammatory, antiapoptotic and antidestructive responses when infected with two ovine isolates of distinct genotype (C and S) or with two C-type isolates from distinct hosts (cattle and sheep); which correlated with the successful survival of these isolates within ovine MDMs. A second objective was to study, based on an in vitro granuloma model, latter stages of the infection by investigating the capacity of two Map isolates from cattle and sheep to trigger formation of microgranulomas. Upon 10 d p.i., both Map isolates were able to induce the formation of granulomas comparable to the granulomas observed in clinical specimens with respect to the cellular components involved. In summary, our results demonstrated that Map isolates from cattle, sheep, goats, deer, fallow-deer and wild boar were able not only to initiate but also to establish a successful infection in ovine macrophages regardless of genotype. PMID- 25111302 TI - Why side-effect outcomes do not affect intuitions about intentional actions: properly shifting the focus from intentional outcomes back to intentional actions. AB - Over the last decade, many articles have suggested that the "badness" of side effect outcomes influences perceivers' intuitions about intentionality, contradicting the traditional notion that mental state inferences lead to moral judgments rather than the reverse. Challenging this assertion, we argue that typically, consideration of intentionality involves thinking about "intentional actions" (things people do) rather than unintended outcomes. Across several studies, we offer an explanatory framework describing why side-effect asymmetries emerge. We first establish that people differentiate actions, outcomes, goals, and side effects, associating intentions with goals but intentionality with actions in furtherance of goals, and that each of these components is readily identified in side-effect scenarios. We then demonstrate that when relationships among actions, goals, and side effects are available for consideration in response options, side-effect effects disappear. We additionally show that, because actions are not explicitly referenced, people reinterpret questions about the intentionality of side effects-particularly for harmful outcomes-as asking about intentional actions that caused side effects, creating a mismatch between participants' pragmatic and researchers' literal interpretations. Finally, we demonstrate how harmful side effects shift perceivers' attention toward considering agents' knowledge/awareness, whereas beneficial side effects focus attention on intentions/motives, which serves a useful social purpose. We discuss how perceptions of intentionality are not influenced by side-effect valence, although, because of structural differences in how people view harm versus benefit, outcomes influence which mental states perceivers consider important when answering questions that are typically asked in side-effects research. Beyond intentionality, we consider how these findings may shed light on trait attribution processes, more generally. PMID- 25111303 TI - Trusting others: the polarization effect of need for closure. AB - Because trust-related issues inherently involve uncertainty, we expected individuals' social-cognitive motivation to manage uncertainty--which is captured by their need for closure--to influence their level of trust in others. Through the results of 6 studies, we showed that higher need for closure was related to more polarized trust judgments (i.e., low trust in distant others and high trust in close others) in the case of both chronic and situational need for closure. Moreover, participants with high need for closure did not revise their level of trust when they received feedback about the trustees' actual trustworthiness, whereas participants with low need for closure did. Overall, our findings indicate that polarized (either high or low, as opposed to moderate) and persistent levels of trust may serve people's seizing and freezing needs for achieving cognitive closure. PMID- 25111304 TI - Too young to correct: a developmental test of the three-stage model of social inference. AB - The 3-stage model of social inference posits that people categorize behaviors and characterize actors or situations effortlessly, but they correct these characterizations with additional information effortfully. The current article tests this model using developmental data, assuming that the less cognitively demanding processes in the model (i.e., categorization, characterization) should appear earlier in development, whereas the more demanding correction process should not appear until later in development. Using 2 different paradigms, Studies 1 and 3 found that younger children failed to take situational information into account while characterizing the actor. Study 2 found that younger children failed to take dispositional information into account while characterizing the situation. In contrast, in these 3 studies, older children used the available information to correct their characterizations of the actors and of the situations. Consistent with the 3-stage model, during elementary school years, children start to integrate additional information when drawing explicit social inferences. In Study 4, children of all age levels used a prior expectancy to draw a dispositional inference, ignoring situational information, suggesting that characterizations based on prior expectancies about an actor are a highly efficient process, not contemplated by the model. The 4 studies together illustrate how developmental data can be valuably used to test adult socio cognitive models, to extend their validity, or to simply further inform those models. PMID- 25111305 TI - Mutual reinforcement between neuroticism and life experiences: a five-wave, 16 year study to test reciprocal causation. AB - High neuroticism predicts psychopathology and physical health problems. Nongenetic factors, including major life events and experiences, explain approximately half of the variance in neuroticism. Conversely, neuroticism also predicts these life experiences. In this study, we aimed to quantify the reciprocal causation between neuroticism and life experiences and to gauge the magnitude and persistence of these associations. This longitudinal cohort study included 5 assessment waves over 16 years in a random sample of 296 Dutch participants (47% women) with a mean age of 34 years (SD = 12, range 16-63 years). Neuroticism was assessed with the Amsterdam Biographic Questionnaire. The experiences measured included positive and negative life events, long-term difficulties (LTDs), and change in life quality, all assessed by contextual rating procedures adapted from the Life Event and Difficulties Schedule. We fit structural equation models in Mplus. Results showed that neuroticism consistently predicted negative experiences, decreased life quality, and LTDs (beta = 0.15 to 0.39), whereas effects on positive experiences were variable (beta = 0.14). LTDs and deteriorated life quality each predicted small but persistent increases in neuroticism (beta = 0.18), whereas improved life quality predicted small but persistent decreases (beta = -0.13). This suggests set point change in neuroticism. Life event aggregates showed no persistent effects on the neuroticism set point. Neuroticism and life experiences showed persistent, bidirectional associations. Experience-driven changes in neuroticism lasted over a decade. Results support the corresponsive principle (reciprocal causation), suggesting a mixed model of change in neuroticism that distinguishes temporary changes in neuroticism from persistent changes in an individual's neuroticism set point. PMID- 25111307 TI - Evaluation of the ecotoxicity of sediments from Yangtze river estuary and contribution of priority PAHs to ah receptor--mediated activities. AB - In this study, in vitro bioassays were performed to assess the ecotoxicological potential of sediments from Yangtze River estuary. The cytotoxicity and aryl hydrocarbon receptor (AhR)-mediated toxicity of sediment extracts with rainbow trout (Oncorhynchus mykiss) liver cells were determined by neutral red retention and 7-ethoxyresorufin-O-deethylase assays. The cytotoxicity and AhR-mediated activity of sediments from the Yangtze River estuary ranged from low level to moderate level compared with the ecotoxicity of sediments from other river systems. However, Yangtze River releases approximately 14 times greater water discharge compared with Rhine, a major river in Europe. Thus, the absolute pollution mass transfer of Yangtze River may be detrimental to the environmental quality of estuary and East China Sea. Effect-directed analysis was applied to identify substances causing high dioxin-like activities. To identify unknown substances contributing to dioxin-like potencies of whole extracts, we fractionated crude extracts by open column chromatography. Non-polar paraffinic components (F1), weakly and moderately polar components (F2), and highly polar substances (F3) were separated from each crude extract of sediments. F2 showed the highest dioxin-like activities. Based on the results of mass balance calculation of chemical toxic equivalent concentrations (TEQs), our conclusion is that priority polycyclic aromatic hydrocarbons indicated a low portion of bio TEQs ranging from 1% to 10% of crude extracts. Further studies should be conducted to identify unknown pollutants. PMID- 25111308 TI - Meta-analysis of apolipoprotein E gene polymorphism and susceptibility of myocardial infarction. AB - A number of case-control studies have been conducted to clarify the association between ApoE polymorphisms and myocardial infarction (MI); however, the results are inconsistent. This meta-analysis was performed to clarify this issue using all the available evidence. Searching in PubMed retrieved all eligible articles. A total of 33 studies were included in this meta-analysis, including 18752 MI cases and 18963 controls. The pooled analysis based on all included studies showed that the MI patients had a decreased frequency of the epsilon2 allele (OR = 0.78, 95% CI = 0.70-0.87) and an increased frequency of the epsilon4 allele (OR = 1.15, 95% CI = 1.10-1.20); The results also showed a decreased susceptibility of MI in the epsilon2epsilon3 vs. epsilon3epsilon3 analysis (OR = 0.79, 95% CI = 0.68-0.90) and in the epsilon2 vs. epsilon3 analysis (OR = 0.78, 95% CI = 0.69 0.89), an increased susceptibility of MI in the epsilon3epsilon4 vs. epsilon3epsilon3 analysis (OR = 1.26, 95% CI = 1.12-1.41), in the epsilon4 vs. epsilon3 analysis (OR = 1.22, 95% CI = 1.12-1.32) and in the epsilon4epsilon4 vs. epsilon3epsilon3 analysis (OR = 1.59, 95% CI = 1.15-2.19). However, there were no significant associations among polymorphisms and MI for the following genetic models: frequency of the epsilon3 allele (OR = 0.99, 95% CI = 0.96-1.02); epsilon2epsilon2 vs. epsilon3epsilon3 analysis (OR = 0.73, 95% CI = 0.40-1.32); or epsilon2epsilon4 vs. epsilon3epsilon3 analysis (OR = 1.10, 95% CI = 0.99 1.21). Our results suggested that the epsilon4 allele of ApoE is a risk factor for the development of MI and the epsilon2 allele of ApoE is a protective factor in the development of MI. PMID- 25111310 TI - New insight into the role of gold nanoparticles in Au@CdS core-shell nanostructures for hydrogen evolution. PMID- 25111309 TI - Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left ventricular dysfunction in a porcine model of chronic myocardial ischemia. AB - BACKGROUND: Although a significant progress has been made in the management of ischemic heart disease (IHD), the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD. METHODS AND RESULTS: We first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle (P<0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32 cycle with 193 mW/cm2 for 20 min, n = 14) at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46+/-4 to 57+/-5%, P<0.05) without any adverse effects, whereas it remained unchanged in the sham group (46+/-5 to 47+/-6%, P = 0.33). Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084+/-175 vs. 858+/-151/mm2, P<0.05). Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78+/-0.2 to 1.39+/-0.4 ml/min/g, P<0.05), but not in the control group (0.84+/-0.3 to 0.97+/ 0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group. CONCLUSIONS: These results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD. PMID- 25111311 TI - Recovering metric properties of objects through spatiotemporal interpolation. AB - Spatiotemporal interpolation (STI) refers to perception of complete objects from fragmentary information across gaps in both space and time. It differs from static interpolation in that requirements for interpolation are not met in any static frame. It has been found that STI produced objective performance advantages in a shape discrimination paradigm for both illusory and occluded objects when contours met conditions of spatiotemporal relatability. Here we report psychophysical studies testing whether spatiotemporal interpolation allows recovery of metric properties of objects. Observers viewed virtual triangles specified only by sequential partial occlusions of background elements by their vertices (the STI condition) and made forced choice judgments of the object's size relative to a reference standard. We found that length could often be accurately recovered for conditions where fragments were relatable and formed illusory triangles. In the first control condition, three moving dots located at the vertices provided the same spatial and timing information as the virtual object in the STI condition but did not induce perception of interpolated contours or a coherent object. In the second control condition oriented line segments were added to the dots and mid-points between the dots in a way that did not induce perception of interpolated contours. Control stimuli did not lead to accurate size judgments. We conclude that spatiotemporal interpolation can produce representations, from fragmentary information, of metric properties in addition to shape. PMID- 25111312 TI - Controlling catalytic selectivity on metal nanoparticles by direct photoexcitation of adsorbate-metal bonds. AB - Engineering heterogeneous metal catalysts for high selectivity in thermal driven reactions typically involves the synthesis of nanostructures with well-controlled geometries and compositions. However, inherent relationships between the energetics of elementary steps limit the control of catalytic selectivity through these approaches. Photon excitation of metal catalysts can induce chemical reactivity channels that cannot be accessed using thermal energy, although the potential for targeted activation of adsorbate-metal bonds is limited because the processes of photon absorption and adsorbate-metal bond photoexcitation are typically separated spatially. Here, we show that the use of sub-5-nanometer metal particles as photocatalysts enables direct photoexcitation of hybridized adsorbate-metal states as the dominant mechanism driving photochemistry. Activation of targeted adsorbate-metal bonds through direct photoexcitation of hybridized electronic states enabled selectivity control in preferential CO oxidation in H2 rich streams. This mechanism opens new avenues to drive selective catalytic reactions that cannot be achieved using thermal energy. PMID- 25111313 TI - Learning curves for robot-assisted and laparoscopic partial nephrectomy. AB - OBJECTIVES: To evaluate the learning curve of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) between two surgeons at a single institution. METHODS: A prospectively maintained, Institutional Review Board (IRB)-approved kidney surgery database was reviewed retrospectively and the first 116 consecutive LPNs performed by one surgeon (Hyung Kim) and 116 consecutive RPNs performed by a second surgeon (Thomas Schwaab) were identified. The learning curve was evaluated by examining the operative times, warm ischemia times (WITs), estimated blood loss, the postoperative estimated glomerular filtration rate (eGFR), and intra- and postoperative complications in the quartiles of 29 patients. The LPNs performed by Hyung Kim were done following completion of a minimally invasive fellowship. Thomas Schwaab had minimal experience with LPN and no fellowship training before starting RAPN. RESULTS: The RAPN and LPN groups had similar patient and tumor characteristics. The RAPN group had a higher preoperative eGFR (74.1+/-22.04 vs. 80.95+/-21.25 mL/minutes, p=0.015) and a worse Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 1+ in 12% vs. 2.6%, p<0.001) compared with the LPN group. Rates of intraoperative (p=0.203) and postoperative (p=0.193) complications were similar. In the RAPN group, operating room (OR) time (161+/-51 vs. 203+/-55 minutes, p<0.001) and WIT (17.7+/-14.8 vs. 21.8+/-9.1 minutes, p<0.001) were shorter. Postoperative stay was longer in the RAPN group (2.4+/-2.2 vs. 1.67+/-1.1 days, p<0.001). The percentage decrease in postoperative eGFR was lower in the RAPN group versus the LPN (9.6% vs. 10%). The learning curves differed for log tumor size, log WIT, and postoperative complications. CONCLUSIONS: The variables of the learning curve for RAPN can be obtained earlier than the same variables for LPN. RAPN had a shorter OR time and WITs. The shorter WITs, earlier in the series, led to consistently lower fluctuations in GFR and preservation of the renal function. The learning curves for each procedure need to be re-evaluated at longer intervals to ensure their accuracy. PMID- 25111314 TI - A 3D aligning method for stimulated emission depletion microscopy using fluorescence lifetime distribution. AB - Optimal resolution by stimulated emission depletion (STED) microscopy requires precise alignment of the donut-shaped depletion focus to the excitation focus. In this article, we demonstrate that fluorescence lifetime distribution can be implemented to align the STED system. Different from the traditional aligning methods in which a scattering imaging module is often equipped, the lifetime based method is free from probable mismatches between the scattering mode and the fluorescent mode, drift errors caused by separate imaging and complex fitting methods. Based on this method, a spatial resolution of 38 nm by time-gated detection has been achieved. PMID- 25111315 TI - New regulatory paradigms for innovative drugs to treat pediatric diseases. PMID- 25111316 TI - Estimation of sodium and potassium intakes assessed by two 24 h urine collections in healthy Japanese adults: a nationwide study. AB - Excess Na intake and insufficient K intake are well-known risk factors for CVD. International comparative studies have reported that Japan has the highest intake of Na and the lowest intake of K in the world. However, no recent study has precisely assessed Na and K intakes in Japanese adults. In the present study, Na and K intakes were estimated from two 24 h urine collections implemented in twenty-three out of forty-seven prefectures in Japan. Apparently healthy men (n 384) and women (n 376), aged 20 to 69 years, who had been working in welfare facilities were recruited, with data collection conducted in February and March 2013. The mean Na excretion was 206.0 mmol/d in men and 173.9 mmol/d in women. The respective values of K excretion were 51.6 and 47.2 mmol/d. The excretion of both Na and K varied considerably among the prefectures, and was higher in subjects with a higher BMI. In contrast, only K excretion was associated with age. After estimating the usual intakes of Na and K, it was found that none of the male subjects met the recommended Na intake values of the WHO, and that only 3.2 % met those of the Japanese government. The respective values for females were 0.1 and 5.0 %. For K intake, 7.5 % of the total subjects met the recommended values of the WHO and 21.7 % met those of the Japanese government. These findings suggest that there is an urgent need for the development of an effective intervention programme to reduce Na intake and promote K intake in the Japanese population. PMID- 25111317 TI - New drugs and treatment targets in psoriasis. AB - In recent years, the increased understanding of the pathophysiology of psoriasis has resulted in several new treatments. The success of ustekinumab proved the importance of the IL-23/T helper cell 17 axis in psoriatic diseases. Several new biologics targeting this axis will reach the clinic in the next years. Biologics are costly, require injections, and some patients experience tacaphylaxis, thus, the development of orally available, small-molecule inhibitors is desirable. Among small-molecules under investigation are A3 adenosine receptor agonists, Janus kinase inhibitors, and phosphodiesterase inhibitors. We review published clinical trials, and conference abstracts presented during the last years, concerned with new drugs under development for the treatment of psoriasis. In conclusion, our psoriasis armamentarium will be filled with several new effective therapeutic options the coming years. We need to be aware of the limitations of drug safety data when selecting new novel treatments. Monitoring and clinical registries are still important tools. PMID- 25111318 TI - Peripartum cardiomyopathy: definition, incidence, etiopathogenesis, diagnosis, and management. AB - Peripartum cardiomyopathy (PPCM) is a serious pregnancy-associated disorder of unknown etiology. The precise cellular and molecular mechanisms underlying PPCM are unclear. A heightened awareness among health care providers can result in early diagnosis of heart failure in late pregnancy and the early postpartum period. Though the symptoms of dyspnea and fatigue can result from normal physiologic changes during pregnancy, an electrocardiogram and brain natriuretic peptide level should be obtained in these patients, in addition to baseline laboratory tests such as a complete blood count, and basic metabolic and hepatic function panels. If the electrocardiogram and brain natriuretic peptide level are abnormal, an echocardiogram should be obtained. The role of endomyocardial biopsy for the diagnosis of PPCM is controversial. Patients should be started on diuretics if volume overloaded, and beta-blockers (preferably metoprolol) if no contraindications exist; angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be avoided during pregnancy or lactation. There are no standard, universally accepted guidelines for the management of PPCM. Although experimental therapies like bromocriptine, pentoxifylline and immunoglobulins have shown promising results, large double-blind randomized trials are essential to confirm the results of smaller studies. In patients with persistent severe left ventricular (LV) dysfunction, advanced therapies like mechanical circulatory support and heart transplantation should be considered. Owing to recent data demonstrating deterioration of LV systolic function after initial recovery, it is essential to maintain long-term follow up of these patients regardless of initial recovery of LV function. We present a comprehensive review of the literature etiopathogenesis, diagnosis, and management of PPCM. PMID- 25111319 TI - Structural biology of cisplatin complexes with cellular targets: the adduct with human copper chaperone atox1 in aqueous solution. AB - Cisplatin is one of the most used anticancer drugs. Its cellular influx and delivery to target DNA may involve the copper chaperone Atox1 protein. Although the mode of binding is established by NMR spectroscopy measurements in solution the Pt atom binds to Cys12 and Cys15 while retaining the two ammine groups-the structural determinants of the adduct are not known. Here a structural model by hybrid Car-Parrinello density functional theory-based QM/MM simulations is provided. The platinated site minimally modifies the fold of the protein. The calculated NMR and CD spectral properties are fully consistent with the experimental data. Our in silico/in vitro approach provides, together with previous studies, an unprecedented view into the structural biology of cisplatin protein adducts. PMID- 25111320 TI - Synthesis of 8-methyl-1-tetralone, a potential intermediate for (+/-) platyphyllide. AB - An alternative method for the synthesis of the 8-methyl-1-tetralone from the commercially available 5-methoxy-1-tetralone has been developed. The transformation involves eight steps and affords an overall yield 25%. PMID- 25111322 TI - Early recognition and treatment of pelvic fractures. PMID- 25111321 TI - Is increased susceptibility to Balkan endemic nephropathy in carriers of common GSTA1 (*A/*B) polymorphism linked with the catalytic role of GSTA1 in ochratoxin a biotransformation? Serbian case control study and in silico analysis. AB - Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates. PMID- 25111323 TI - Anatomy of the left main coronary artery of particular relevance to ablation of left atrial and outflow tract arrhythmias. AB - BACKGROUND: Left main coronary artery (LMCA) damage is a rare but catastrophic complication of cardiac ablation procedures. OBJECTIVE: The purpose of this study was to describe the anatomic relationships of the LMCA to its adjacent structures using analysis of computed tomographic coronary angiograms (CTCA). METHODS: We studied 100 patients (55 males, age 51 +/- 10 years) who were investigated for chest pain with CTCA. The relationships between the LMCA and adjacent structures were described by analysis of 2-dimensional images and 3-dimensional reconstructions. RESULTS: The LMCA coursed within 5 mm of the anterior left atrial endocardium and/or base of left atrial appendage in 49% (within 2 mm in 17%) and from the pulmonary artery in 90% (within 2 mm in 43%). The LMCA was within 5 mm of the right ventricular outflow tract in 1%. In 4% the LMCA coursed inferiorly, remaining within 5 mm of the left aortic sinus of Valsalva at a vertical distance >5 mm from the inferior margin of the LMCA ostium. CONCLUSION: The LMCA is often intimately related to the anterior left atrium, left atrial appendage base, and pulmonary artery and occasionally to the inferior part of the left aortic sinus of Valsalva and thus is exposed to the risk of injury during ablation in these areas. The LMCA is rarely close to the right ventricular outflow tract. PMID- 25111324 TI - Major predictors of fibrous adherences in transvenous implantable cardioverter defibrillator lead extraction. AB - BACKGROUND: Percutaneous removal of implantable cardioverter-defibrillator (ICD) leads is a difficult procedure because of the consequence of massive fibrous tissue growth along the lead. OBJECTIVE: The purpose of this study was to describe the occurrence and location of fibrous adherences in ICD lead extraction and to identify potential predictors among patient and lead characteristics. METHODS: We studied 637 consecutive patients who underwent transvenous extraction of 678 ICD leads from 1997 to 2013. RESULTS: Procedural success rate was 99%, without major complications. Areas of adherence were found in the subclavian vein (78%), innominate vein (65%), superior vena cava (66%), and heart (73%). Dwell time, passive fixation, and dual-coil lead design were independently associated with adherences. Dual-coil lead design was associated with adherences in the innominate vein and superior vena cava, whereas coil treatment (eg, expandable polytetrafluoroethylene-coated or medical adhesive back-filled strategies) prevented adherences. Passive fixation mechanism was associated with adherences in the heart. CONCLUSION: ICD leads, after long dwell-time, are affected by fibrous adherences uniformly distributed along the lead course. Lead features represent major predictors of the phenomenon. Careful lead selection is recommended at the time of implantation to prevent adherences. In addition, lead related risk stratification is mandatory before a transvenous extraction procedure. PMID- 25111325 TI - Second coupling interval of nonsustained ventricular tachycardia to distinguish malignant from benign outflow tract ventricular tachycardias. AB - BACKGROUND: Idiopathic ventricular tachycardia (VT) originating from the outflow tract (OT) usually is considered a benign condition. In rare cases, patients with OT-VT suffer from syncope or even sudden cardiac death. OT-VT is frequently preceded by nonsustained VT (NSVT). OBJECTIVE: The purpose of this study was to clarify if the ECG parameters of NSVTs could differentiate malignant from benign OT-VT. METHODS: We retrospectively evaluated patients without structural heart disease who had documented OT-NSVT on ECG. ECG parameters were compared between patients with syncope, aborted sudden cardiac death, or ventricular fibrillation (malignant group, n = 36) and patients without syncope (benign group, n = 40). RESULTS: There were no differences with regard to age and gender between the malignant and benign groups. On analysis of NSVT, the first coupling interval (CI) of NSVT was comparable between the 2 groups (458 +/- 87 ms vs 485 +/- 95 ms, P = .212). However, the second CI of NSVT beats was significantly shorter in the malignant group (313 +/- 58 ms vs 385 +/- 83 ms, P < .0001). During 48-month follow-up, the benign group had a significantly lower recurrence of clinical VT than the malignant group (P = .046). The malignant group frequently had more than 1 focus of VT, whereas the benign group showed only a single focus (1.82 vs 1.09, P = .023). CONCLUSION: The second CI of NSVT in the malignant group was significantly shorter than that of the benign OT-VT group. Careful measurement of the second CI of NSVT may help identify the malignant form of OT-VT, enabling early treatment to prevent future cardiac events. PMID- 25111326 TI - Time outside of therapeutic range in atrial fibrillation patients is associated with long-term risk of dementia. AB - BACKGROUND: The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. One possibility is that exposure to chronic microembolism or microbleeds results in repetitive cerebral injury that is manifest by cognitive decline. OBJECTIVE: The purpose of this study was to test the hypothesis that AF patients with a low percentage of time in the therapeutic range (TTR) are at higher risk for dementia due to under- or overanticoagulation. METHODS: Patients anticoagulated with warfarin (target international normalized ratio [INR] 2-3), managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service with no history of dementia or stroke/transient ischemic attack, were included in the study. The primary outcome was dementia incidence defined by ICD-9 codes. Percent time in TTR was calculated using the method of linear interpolation and stratified as >75%, 51%-75%, 26%-50%, and <=25%. Multivariable Cox hazard regression was used to determine dementia incidence by percentage categories of TTR. RESULTS: A total of 2605 patients (age 73.7 +/- 10.8 years, 1408 [54.0%] male) were studied. The CHADS2 score distribution was 0: 216 (8.3%); 1: 579 (22.2%); 2: 859(33.0%); 3: 708 (27.2%); and >=4: 243 (9.3%). The percent TTR averaged 63.1 +/- 21.3, with percent INR <2.0: 25.6% +/- 17.9% and percent INR >3.0: 16.2% +/- 13.6%. Dementia was diagnosed in 109 patients (4.2%) (senile: 37 [1.4%]; vascular: 8 [0.3%]; Alzheimer: 64 (2.5%]). After adjustment, decreasing categories of percent TTR were associated with increased dementia risk (vs >75%): <25%: hazard ratio (HR) 5.34, P < .0001; 26%-50%: HR 4.10, P < .0001; and 51%-75%: HR = 2.57, P = .001. CONCLUSION: Quality of anticoagulation management represented as percent TTR among AF patients without dementia was associated with dementia incidence. These data support the possibility of chronic cerebral injury as a mechanism that underlies the association of AF and dementia. PMID- 25111327 TI - If inhibition in the atrioventricular node by ivabradine causes rate-dependent slowing of conduction and reduces ventricular rate during atrial fibrillation. AB - BACKGROUND: If channels are functionally expressed in atrioventricular (AV) nodal tissue. OBJECTIVE: The purpose of this study was to address whether the prototypical If inhibitor, ivabradine, at clinically safe concentrations can slow AV node conduction to reduce ventricular rate (VR) during atrial fibrillation (AF). METHODS: Effects of ivabradine (0.1 mg/kg i.v. bolus) were studied in an anesthetized Yorkshire pig (N = 7) model of AF and in isolated guinea pig hearts (N = 7). RESULTS: Ivabradine reduced heart rate (P = .0001) without affecting mean arterial pressure during sinus rhythm. The agent lengthened PR intervals in a rate-dependent manner (P = .0009) by 14 +/- 2.7 ms (P = .003) and 25 +/- 3.0 ms (P = .0004) and increased atrial-His (A-H) intervals in a rate-dependent manner (P = .020) by 10 +/- 1.7 ms and 17 +/- 2.8 ms during pacing at 130 and 180 bpm, respectively (both P = .0008). Similar rate-dependent effects were observed in isolated guinea pig hearts. Ivabradine slowed VR during AF from 240 +/- 21 bpm to 211 +/- 25 bpm (P = .041). The ivabradine-induced increase in A-H interval was inversely correlated with VR (r = -0.85, P = .03, at 130 bpm; r = -0.95, P = .003, at 180 bpm). QT and HV intervals, AF dominant frequency (8.5 +/- 0.9 to 8.7 +/- 1.1 Hz, P = NS), mean arterial pressure, and left ventricular dP/dt (1672 +/- 222 to 1889 +/- 229 mm Hg/s, P = NS) during AF were unaffected. CONCLUSION: Ivabradine's rate-dependent increase in A-H interval is highly correlated with VR during AF. As dominant frequency was unaltered, AV node conduction slowing during high nodal activation rates appears to be the main mechanism of ivabradine's VR reduction. If inhibition in the AV node may provide a promising target to slow VR during AF without depression in contractility. PMID- 25111328 TI - Isolated polycystic morphology: Does it affect the IVF treatment outcomes? AB - The aim of the current study was to compare women who have normal ovarian ultrasonographic findings and women with ovulatory polycystic ovary (PCO), in terms of IVF treatment outcome. The study was conducted at a tertiary referral hospital and included 906 women who underwent IVF treatment. Of these, 224 of the women had PCO (24.7%) and 682 of the women had normal ovarian morphology (75.3%) at the time of ultrasonographic examination prior to IVF. The treatment outcomes were compared between the two groups. In the PCO group, the number of oocytes at the size of > 16 mm, the overall number of collected oocytes and the number of fertilised oocytes were found to be significantly higher. Furthermore, the rates of implantation, biochemical pregnancy and clinical pregnancy were significantly higher in the PCO group (p < 0.05). The detection of PCO morphology on baseline ultrasonography in IVF candidates may be associated with higher treatment success. PMID- 25111331 TI - Graphene/graphite sheet assisted growth of high-areal-density horizontally aligned carbon nanotubes. AB - We report a facile graphene/graphite sheet assisted CVD process for the synthesis of high-areal-density HACNT arrays. Besides, some metal nanoparticles could eat the graphene/graphite sheets, forming serpentine holes on the sheets in the early stage, and finally leading to the precipitation of CNTs without an additional carbon source. PMID- 25111330 TI - Assessment of molecular testing in fine-needle aspiration biopsy samples: an experience in a Chinese population. AB - Fine-needle aspiration biopsy remains the mainstay for preoperative examination of thyroid nodules; however, it does not provide a definite diagnosis in up to 25% of nodules. Considerable studies have been performed to identify molecular markers to resolve this diagnostic dilemma. The aim of this study was to establish the distribution and frequency of common genetic alterations in a comprehensive set of benign and malignant thyroid nodules, and to determine the feasibility and role of testing for a panel of genetic alterations in improving the accuracy of cytology diagnosis in a Chinese population. This study was conducted in 314 thyroid nodules comprising 104 papillary thyroid carcinomas, 13 suspicious nodules, 52 indeterminate nodules, and 145 benign nodules. Point mutations and RET/PTC rearrangements, were evaluated by pyrosequencing and TaqMan real-time PCR, respectively. After surgery, 115 nodules were confirmed as conventional papillary thyroid carcinoma and 102 (88.70%) of these nodules harbored either the BRAF(V600E) mutation (76.52%) or RET/PTC rearrangements (12.17%). RAS mutation was found in 1 (33.33%) follicular thyroid carcinoma, 1 (14.29%) follicular thyroid adenoma and 4 (10%) goiter nodules. With cytology and molecular testing, the diagnostic accuracy was further increased to 98.82% in papillary thyroid carcinoma diagnosis, and was preoperatively increased to 76.92% and 84.00%, respectively, in nodules with suspicious and indeterminate cytology. In conclusion, molecular testing of a panel of genetic alterations in fine-needle aspiration biopsy can be effectively performed in clinical practice. It enhances the accuracy of cytology and is of particular value for indeterminate nodules in the Chinese population. PMID- 25111332 TI - How frustrated Lewis acid/base systems pass through transition-state regions: H2 cleavage by [tBu3P/B(C6F5)3]. AB - We investigate the transition-state (TS) region of the potential energy surface (PES) of the reaction tBu3P + H2 + B(C6F5)3 -> tBu3P-H(+) + (-)H-B(C6F5)3 and the dynamics of the TS passage at room temperature. Owing to the conformational inertia of the phosphane???borane pocket involving heavy tBu3P and B(C6F5)3 species and features of the PES E(P???H, B???H | B???P) as a function of P???H, B???H, and B???P distances, a typical reactive scenario for this reaction is a trajectory that is trapped in the TS region for a period of time (about 350 fs on average across all calculated trajectories) in a quasi-bound state (scattering resonance). The relationship between the timescale of the TS passage and the effective conformational inertia of the phosphane???borane pocket leads to a prediction that isotopically heavier Lewis base/Lewis acid pairs and normal counterparts could give measurably different reaction rates. Herein, the predicted quasi-bound state could be verified in molecular collision experiments involving femtosecond spectroscopy. PMID- 25111333 TI - The relative contribution of edema and hemorrhage to raised intrathecal pressure after traumatic spinal cord injury. AB - Raised intrathecal pressure (ITP) after traumatic spinal cord injury (SCI) is a critically important aspect of injury development that may result in significantly greater tissue damage and worsened functional outcome. Raised ITP is caused by the accumulation of blood and/or water (edema), and while their occurrence after traumatic SCI has been well established, the relative contribution of both processes to the development of ITP after SCI has not yet been determined. Accordingly, the current study investigates the temporal profile of raised ITP after traumatic SCI in relation to both hemorrhage and edema development. A closed balloon compression injury was induced at T10 in New Zealand White rabbits. Animals were thereafter assessed for spinal water content (edema), ITP, lesion and hemorrhage volume, and albumin immunoreactivity from 5 h to 1 week post-SCI. Early increases in ITP at 5 h post-injury were associated with significant increases in blood volume. ITP, however, was maximal at 3 days post-SCI, at which time there was an associated significant increase in edema that persisted for 1 week. We conclude that raised ITP after traumatic SCI is initially driven by volumetric increases in hemorrhage, while edema becomes the primary driver of ITP at 3 days post-injury. PMID- 25111334 TI - Nrf2 augments skeletal muscle regeneration after ischaemia-reperfusion injury. AB - Skeletal muscles harbour a resident population of stem cells, termed satellite cells (SCs). After trauma, SCs leave their quiescent state to enter the cell cycle and undergo multiple rounds of proliferation, a process regulated by MyoD. To initiate differentiation, fusion and maturation to new skeletal muscle fibres, SCs up-regulate myogenin. However, the regulation of these myogenic factors is not fully understood. In this study we demonstrate that Nrf2, a major regulator of oxidative stress defence, plays a role in the expression of these myogenic factors. In both promoter studies with myoblasts and a mouse model of muscle injury in Nrf2-deficient mice, we show that Nrf2 prolongs SC proliferation by up regulating MyoD and suppresses SC differentiation by down-regulating myogenin. Moreover, we show that IL-6 and HGF, both factors that facilitate SC activation, induce Nrf2 activity in myoblasts. Thus, Nrf2 activity promotes muscle regeneration by modulating SC proliferation and differentiation and thereby provides implications for tissue regeneration. PMID- 25111335 TI - Extinction and reinstatement of phasic dopamine signals in the nucleus accumbens core during Pavlovian conditioning. AB - The prediction-error model of dopamine (DA) signaling has largely been confirmed with various appetitive Pavlovian conditioning procedures and has been supported in tests of Pavlovian extinction. Studies have repeatedly shown, however, that extinction does not erase the original memory of conditioning as the prediction error model presumes, putting the model at odds with contemporary views that treat extinction as an episode of learning rather than unlearning of conditioning. Here, we combined fast-scan cyclic voltammetry (FSCV) with appetitive Pavlovian conditioning to assess DA release directly during extinction and reinstatement. DA was monitored in the nucleus accumbens core, which plays a key role in reward processing. Following at least 4 daily sessions of 16 tone food pairings, fast-scan cyclic voltammetry was performed while rats received additional tone-food pairings followed by tone alone presentations (i.e., extinction). Acquisition memory was reinstated with noncontingent presentations of reward and then tested with cue presentation. Tone-food pairings produced transient (1- to 3-s) DA release in response to tone. During extinction, the amplitude of the DA response decreased significantly. Following presentation of 2 noncontingent food pellets, subsequent tone presentation reinstated the DA signal. Our results support the prediction-error model for appetitive Pavlovian extinction but not for reinstatement. PMID- 25111337 TI - The role of the medial prefrontal cortex in regulating interanimal coordination of movements. AB - Rats with juvenile play experience display a greater ability in coordinating their movements with social partners than those deprived of such experience, and this may be due to the play-induced neural restructuring of the medial prefrontal cortex (mPFC). The present study investigates the role of the mPFC in interanimal coordination. Rats with and without bilateral mPFC lesions were tested on a robbing-and-dodging task. This food protection task measures the ability of rats to protect pieces of food by gaining and maintaining an interanimal distance between themselves and the rat attempting to rob the food. Given that mPFC lesions have been associated with sensory and motor deficits, the same rats were also subjected to a task to measure skilled motor movements. Rats with bilateral mPFC lesions had more food stolen and displayed an inability to maintain interanimal distance with partner, but did not exhibit any motor or sensory deficits. These findings suggest that the mPFC is involved in interanimal coordination and that the play-induced neural restructuring of this area may account for the enhanced coordination seen in rats with prior play experience. PMID- 25111336 TI - Age-related spatial working memory deficits in homing pigeons (Columba livia). AB - The hippocampus is particularly susceptible to age-related degeneration that, like hippocampal lesions, is thought to lead to age-related decline in spatial memory and navigation. Lesions to the avian hippocampal formation (HF) also result in impaired spatial memory and navigation, but the relationship between aging and HF-dependent spatial cognition is unknown. To investigate possible age related decline in avian spatial cognition, the current study investigated spatial working memory performance in older homing pigeons (10+ years of age). Pigeons completed a behavioral procedure nearly identical to the delayed spatial, win-shift procedure in a modified radial arm maze that has been previously used to study spatial working memory in rats and pigeons. The results revealed that the older pigeons required a greater number of choices to task completion and were less accurate with their first 4 choices as compared to younger pigeons (1-2 years of age). In addition, older pigeons were more likely to adopt a stereotyped sampling strategy, which explained in part their impaired performance. To the best of our knowledge, this study is the first to demonstrate an age-related impairment of HF-dependent, spatial memory in birds. Implications and future directions of the findings are discussed. PMID- 25111338 TI - Ferro- to antiferromagnetic crossover angle in diphenoxido- and carboxylato bridged trinuclear Ni(II)2-Mn(II) complexes: experimental observations and theoretical rationalization. AB - Three new trinuclear heterometallic Ni(II)-Mn(II) complexes have been synthesized using a [NiL] metalloligand, where H2L = N,N'-bis(salicylidene)-1,3 propanediamine. The complexes [(NiL)2Mn(OCnn)2(CH3OH)2].CH3OH (1), [(NiL)2Mn(OPh)2(CH3OH)2][(NiL)2Mn(OPh)2].H2O (2), and [(NiL)2Mn(OSal)2(CH3OH)2].2[NiL] (3) (where OCnn = cinnamate, OPh = phenylacetate, OSal = salicylate) have been structurally characterized. In all three complexes, in addition to the double phenoxido bridge, the two terminal Ni(II) atoms are linked to the central Mn(II) by means of a syn-syn bridging carboxylate, giving rise to a linear structure. Complexes 1 and 2 with Ni-O-Mn angles of 97.24 and 96.43 degrees , respectively, exhibit ferromagnetic interactions (J(Ni-Mn) = +1.38 and +0.50 cm(-1), respectively), whereas 3 is antiferromagnetic (J(Ni-Mn) = -0.24 cm(-1)), having an Ni-O-Mn angle of 98.51 degrees . DFT calculations indicate that there is a clear magneto-structural correlation between the Ni-O-Mn angle and J(Ni-Mn) values, which is in agreement with the experimental results. PMID- 25111340 TI - Structural studies of nonionic dodecanol ethoxylates at the oil-water interface: effect of increasing head group size. AB - The conformation of charged surfactants at the oil-water interface was recently reported. With the aim to assess the role of the head group size on the conformation of the adsorbed layer, we have extended these studies to a series of nonionic dodecanol ethoxylate surfactants (C12En, ethylene oxide units n from 6 to 12). The study was performed using neutron reflectometry to enable maximum sensitivity to buried interfaces. Similarly to charged surfactants, the interface was found to be broader and rougher compared to the air-water interface. Irrespective of the head group size, the tail group region was found to assume a staggered conformation. The conformations of the head group were found to be significantly different from those of the air-water interface, moving from a globular to an almost fully extended conformation at the oil-water interface. The stretching of the head groups is attributed to the presence of some hexadecane oil molecules, which may penetrate all the way to this region. It is proposed here that the presence of the oil, which can efficiently solvate the surfactant tail groups, plays a key role in the conformation of the adsorbed layer and is responsible for the broadening of the interface. PMID- 25111339 TI - Gender-dependent effects of maternal immune activation on the behavior of mouse offspring. AB - Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the "maternal immune activation" model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior. PMID- 25111341 TI - Management of trichilemmal carcinoma: an update and comprehensive review of the literature. AB - BACKGROUND: Trichilemmal carcinoma (TC) is a rare malignant adnexal neoplasm with outer root sheath differentiation. Most cases have been treated by surgical excision with a few recurrences. There have been 6 case reports of TC treated with Mohs micrographic surgery (MMS). OBJECTIVE: To perform an updated review of the literature regarding management of this uncommon tumor. METHODS: A comprehensive literature review was conducted by searching the PubMed database using the keywords trichilemmal carcinoma, tricholemmal carcinoma, and tricholemmocarcinoma. RESULTS: There have been 103 reported cases of TC, and most of these were treated with surgical excisions. Of the 35 cases with follow-up data, 3 reported local recurrences and 1 had subsequent metastatic disease. There are 6 cases of TC successfully treated with MMS without any recurrence. In addition, we report the seventh case of TC successfully treated with MMS. Other reported treatment modalities include imiquimod and excision with frozen sections. Histopathologically, the distinction between TC and squamous cell carcinoma with clear cell differentiation has been debated in the literature. CONCLUSION: Trichilemmal carcinoma is a rare neoplasm that may behave aggressively. The recommended treatment should be a complete surgical excision with histologic confirmation of clear margins. In cases where tissue sparing or cosmesis is important, MMS may be considered. PMID- 25111342 TI - Statistical evaluation of dermoscopic features in basal cell carcinomas. AB - BACKGROUND: Early detection of basal cell carcinoma (BCC) is of crucial importance, as serious morbidity may result from undiagnosed tumor. OBJECTIVE: To evaluate diagnostic significance (specificity, sensitivity, positive and negative predictive value) of dermoscopic features in BCCs. METHODS: A prospective observational study was conducted using contact polarized dermoscopy to evaluate the presence of various dermoscopic features. Images were evaluated for a range of dermoscopic colors, structures, and vessels. SETTING: Specialized University Clinic. PATIENTS: A sample of 151 histopathologically verified BCCs was collected from 116 patients (64 males and 52 females). The populations included predominantly Caucasian individuals. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive and negative predictive values of the various dermoscopic features seen in BCCs were calculated according to standard formulas. RESULTS: The highest diagnostic value (specificity [Sp] = 100%, positive predictive value [PPV] = 100%) for BCC had spoke-wheel areas, short fine telangiectasias, white rosette, annular hypopigmentation, multiple erosions, and ulceration. Arborizing vessels (Sp = 96%, PPV = 98%) and microvessels (Sp = 93%, PPV = 97%) had significant diagnostic value for BCC. Annular distribution of telangiectatic vessels (Sp = 96%), translucency (Sp = 93%), and multiple blue-gray globules (Sp = 89%) had the same PPV of 95% for BCCs. Other dermoscopic features of this study are not strongly associated with the diagnosis of BCC. CONCLUSION: Dermoscopic features relevant for diagnosis of BCC have different diagnostic "weight." Clinicians should have known the sensitivity and specificity of each relevant feature before they can make an accurate dermoscopic diagnosis of BCC. PMID- 25111343 TI - Dermoscopic features in different morphologic types of basal cell carcinoma. AB - BACKGROUND: Many different phenotypic presentations of basal cell carcinoma (BCC) are possible. OBJECTIVE: This study aims to highlight the similarities and differences in dermoscopic features between different morphologic types of BCC. METHODS: A prospective observational study was performed using contact polarized dermoscopy to evaluate the presence of various dermoscopic features. Images were evaluated for a range of dermoscopic colors, structures, and vessels. Features were compared according to the histopathologic subtype. RESULTS: Of the 151 BCCs, 39.7% were nodular, 37.7% superficial, 13.9% ulcerated, 3.97% pigmented, 2.65% morpheaform, and 1.99% infiltrative BCCs. The dermoscopic features that showed a highly significant difference (p < .001) in distribution between various histologic groups were large blue-gray ovoid nests, leaf-like areas, arborizing vessels, short fine telangiectasias, annular distribution of telangiectatic vessels, structureless hypopigmentation, annular hypopigmentation, translucency, multiple erosions, and ulceration. A significant difference (p < .05) between evaluated groups was found in structureless hyperpigmentation, arborizing microvessels, milky red background, and pigment network. CONCLUSION: The results of the study indicate that the combination of relevant dermoscopic features in different morphologic types of BCC depends on the thickness of the tumor, and not on its histologic nature. In addition, dermoscopy was shown to be not particularly useful in identifying which BCCs are more aggressive. PMID- 25111344 TI - History of laser ablation in pigmented basal cell carcinoma conceals classic dermoscopic patterns. AB - BACKGROUND: Some patients with pigmented basal cell carcinoma (pBCC) had a history of laser ablation after misdiagnosis, which may conceal the dermoscopic clues of malignancy. OBJECTIVE: The objective of this study was to investigate the question of whether the classic and nonclassic dermoscopic patterns of BCCs may be concealed by past laser ablation. METHODS: Classic and nonclassic dermoscopic patterns were examined in 55 pBCC patients with a history of laser ablation and another 150 control pBCC patients. RESULTS: All but 4 of the study patients (92.3%) showed at least 1 classic pattern of BCC, whereas every control patient showed more than 1 classic pattern (p = .995). Compared with the control group, the detection rate of large blue/gray ovoid nests, multiple blue/gray globules, and ulceration was found to be significantly decreased in the study group (p < .05). However, 4 patients who lacked classic patterns showed at least 1 nonclassic pattern. CONCLUSION: Previous laser ablation in pBCC may conceal the classic dermoscopic patterns by reducing the detection rate. Therefore, more prudent and detailed dermoscopic monitoring is required in suspected cases of pBCC, especially in patients with a history of laser ablation. PMID- 25111345 TI - Reconstruction of the external auditory canal using the random flap technique and laser Doppler evaluation. AB - BACKGROUND: The external auditory canal is one of the most difficult sites to reconstruct after tumor resection. In general, fascia transplantation is used to reconstruct defects of the external auditory canal, but this method is associated with scar formation and prolonged wound healing. Scar tissue might cause stenosis in the external auditory canal and hypoacusis, and wound healing is further delayed by radiation and chemotherapy. OBJECTIVE: To examine the safety of a random flap for reconstruction of an external auditory canal based on blood flow evaluation using a laser Doppler system. METHODS: Ten healthy volunteers were enrolled in this study to compare blood flow in the face, back, and behind the ear using a laser Doppler system. Two cases of external auditory canal reconstruction are presented. RESULTS: Blood flow behind the ear was abundant compared with that in the back. Blood flow in the face was higher than that behind the ear or on the back. CONCLUSION: Blood flow in the random flap was easily evaluated using the laser Doppler method. Based on our findings, we propose the random flap to reconstruct the external auditory canal after tumor resection. PMID- 25111346 TI - Midface-lift with lateral orbicularis oculi flap excision or imbrication. AB - BACKGROUND: The orbicularis oculi advancement midface-lift treats rhytides and infraorbital grooves. The muscle flap smoothes the subciliary lid and cheek zone but may produce contour abnormalities laterally. OBJECTIVE: To describe a technique of orbicularis flap midface-lift with excision or imbrication of muscle and to evaluate the results--to include characterizing the lateral contour abnormalities--in a large series. MATERIALS AND METHODS: A total of 108 patients received a primary aesthetic orbicularis advancement flap midface-lift. Two masked observers scored each patient's result based on preoperative and postoperative images. Patients also scored their satisfaction of the results of their procedures. Patient age, sex, surgical technique specifics (i.e., excision or imbrication), and complications were recorded. RESULTS: All patients had favorable aesthetic improvement scores with no significant complications. In patients who received orbicularis excision (N = 33), lateral hollowing occurred in 3 patients; none desired correction. With an imbrication technique (N = 75), lateral mounding occurred in 6 patients; 3 of these patients were treated with elliptical excision. CONCLUSION: Orbicularis advancement midface-lifting was safe and effective in rejuvenating the midface in this series. Aesthetic complications were infrequent but include lateral hollowing when orbicularis is excised and lateral mounding with muscle imbrication. PMID- 25111347 TI - Combined use of monopolar radiofrequency and transdermal drug delivery in the treatment of melasma. AB - BACKGROUND: Melasma is a common acquired pigmentary disorder that has a considerable psychological impact on the patient. The recurrent and refractory nature of this condition makes it difficult for treatment. OBJECTIVE: We aim to evaluate the efficacy and safety of a combined system that simultaneously uses monopolar radiofrequency (RF) and transdermal drug delivery of phytocomplex containing 1% kojic acid in the treatment of melasma. MATERIALS AND METHODS: Fifty patients affected by melasma underwent 6 sessions of treatment at 1-week intervals. The outcome was evaluated before treatment (T0) and 1 month (T1) and 6 months (T2) after treatment using the Melasma Area and Severity Index score, a Mexameter, and Visioface devices for digital and ultraviolet computerized image analysis of skin color. RESULTS: The image analysis showed that hyperpigmentation was significantly reduced at T1 and T2 compared with baseline. Melasma Area and Severity Index score, the average melanin score, and the average erythema values showed a significant reduction. No side effects were observed or reported. CONCLUSION: This study describes the first report of improvement in melasma through the combined use of monopolar RF with transdermal delivery of depigmenting agents. This could be a safe, tolerable, and effective alternative tool for the treatment of melasma. PMID- 25111348 TI - Treatment of skin laxity using multisource, phase-controlled radiofrequency in Asians: visualized 3-dimensional skin tightening results and increase in elastin density shown through histologic investigation. AB - BACKGROUND: A new multisource phase-controlled radiofrequency (MPCRF) device is widely used for skin tightening and rejuvenation in Asia. OBJECTIVE: To evaluate the efficacy of MPCRF objectively and histologically. METHODS: An MPCRF device with real-time impedance control was evaluated. Ten Japanese patients were treated one side of the face, and the untreated side served as a control. Three dimensional (3-D) imaging was performed to evaluate the posttreatment volume change. An independent observer assessed the 3-D images. Histologic evaluations of elastin were performed by Victoria Blue staining in 5 Japanese patients. RESULTS: Objective assessments evaluated by a 3-D color schematic representation showed improvement in skin laxity after the final treatment in all patients. The treated side improved markedly compared with the untreated side; however, even the untreated side slightly improved. The elastin density was significantly increased compared with controls in all 5 Japanese patients (p = .0013). Induced elastin appeared to be relatively thin elastic fibers without irregular elastic fibers, such as solar elastosis. Side effects were not observed, and the patients reported feeling comfortable throughout the study. CONCLUSION: Multisource phase controlled radiofrequency treatments provide stimulation of elastin and skin tightening results safely and effectively, and thus are beneficial for improving skin laxity and rhytides. PMID- 25111349 TI - Novel treatment of nail psoriasis using the intense pulsed light: a one-year follow-up study. AB - BACKGROUND: Pulsed dye laser has been used successfully in the treatment of nail psoriasis. Intense pulsed light (IPL) has been used in the treatment of plaque psoriasis using a 550-nm filter. OBJECTIVE: To study the efficacy of IPL in the treatment of nail psoriasis. PATIENTS AND METHODS: Twenty patients with finger and toe nail psoriasis were treated by IPL. Sessions were performed every 2 weeks for a maximum of 6 months. The Nail Psoriasis Severity Index (NAPSI) score was calculated at baseline and 1 month after the last treatment session. Follow-up was performed at 1, 6, and 12 months. RESULTS: Patients received a mean of 8.63 +/- 3.6 IPL sessions. After treatment, there was significant improvement in the nail bed and matrix (p < .0001), and in the NAPSI (p < .0001). Nail bed showed improvement by 71.2%, whereas the nail matrix improvement was only 32.2%. The total NAPSI was 82.4%. Patient follow-up revealed relapse in 3 patients after 6 months. CONCLUSION: Intense pulsed light is a promising effective modality of treatment of nail psoriasis, which is easy to use, safe, and provide a long period of remission. This was confirmed by the elicited clinical improvement, NAPSI, and patient satisfaction. PMID- 25111350 TI - Prevention of excessive endothelin-1 release in sclerotherapy: in vitro and in vivo studies. AB - BACKGROUND: The foam sclerotherapy technique has become one of the most commonly used treatments for superficial venous insufficiency. Despite excellent results, few visual/neurologic disturbances have been recently reported; their pathogenesis is still debated but a correlation with endothelin-1 (ET-1) release from the treated vein has been proposed. OBJECTIVE: The purpose of this work was to evaluate the ET-1 release after sclerotherapy and to investigate the effects of the anti-endothelin drug aminaphtone. METHODS AND MATERIALS: As in vitro sclerotherapy model, an endothelial cell culture, mimicking vascular endothelium, was pretreated with aminaphtone and exposed to detergents. Cell survival and ET-1 release were measured. In in vivo experiments, 45 rats, fed with different aminaphtone-rich diets, were subjected to sclerotherapy, and the systemic ET-1 was measured. RESULTS: Aminaphtone cell exposure caused a statistically significant reduction in ET-1 release, both before and after in vitro sclerotherapy. Rats fed with aminaphtone showed a trend toward reduced mortality and a significant decrease of ET-1 release after sclerotherapy. CONCLUSION: This is the first study in which an anti-endothelin agent was able to cause a significant reduction of ET-1 release during sclerotherapy. Although clinical studies are required, these findings might advocate the use of anti-endothelin agents in prophylaxis of neurologic or visual disturbances after sclerotherapy. PMID- 25111351 TI - Efficacy of incobotulinumtoxinA for treatment of glabellar frown lines: a post hoc pooled analysis of 2 randomized, placebo-controlled, phase 3 trials. AB - BACKGROUND: Botulinum neurotoxin type A trials in aesthetic indications have used differing efficacy parameters and responder definitions. OBJECTIVE: To analyze the treatment efficacy and duration of incobotulinumtoxinA for glabellar frown lines using pooled data from 2 large, Phase 3, placebo-controlled trials, and end points similar to those used in previous botulinum neurotoxin type A studies. MATERIALS AND METHODS: IncobotulinumtoxinA and placebo groups comprised 366 and 181 subjects, respectively. The efficacy of a single 20-U treatment of incobotulinumtoxinA or placebo was evaluated by investigator-assessed and subject assessed responder rates (>= 1-point improvement from baseline), mean score, and mean change from the baseline glabellar frown line severity score. RESULTS: At all follow-up visits, responder rates and mean change from the baseline score (investigator-assessed and subject-assessed) were significantly greater for incobotulinumtoxinA versus placebo (p < .0001). The maximum investigator-assessed responder rate (93.1%) was achieved at Day 30 after treatment, when the mean improvement on the 4-point facial wrinkle scale peaked at 1.88. Treatment effect declined over time but the investigator-assessed responder rate was 45.7% at the end of the study. CONCLUSION: Superiority of incobotulinumtoxinA over placebo for treating glabellar frown lines was confirmed. IncobotulinumtoxinA achieved a maximum responder rate of 93.1% and a long duration of treatment effect: 45.7% of subjects showed efficacy at 120 days. PMID- 25111352 TI - Quantifying soft tissue loss in the aging male face using magnetic resonance imaging. AB - BACKGROUND: Quantitative data on soft tissue aging of the face are scarce, particularly in men. OBJECTIVE: Magnetic resonance imaging (MRI) was used to quantify and compare facial soft tissue loss in men. MATERIALS AND METHODS: Two thousand thirty-seven MRIs were screened and 30 male subjects were divided into young, middle, and old-aged groups. A blinded radiologist measured temporal, infraorbital, and medial and lateral cheek areas. RESULTS: The mean thickness of the subcutaneous tissue in the temporal area was 12.5, 10.9, and 9.6 mm in the young, middle, and older age groups, respectively (p < .001). A 40% reduction in the skin thickness was seen in the infraorbital areas. Finally, a decrease of 1.5 and 2.7 mm in medial cheeks (p < .001), and 0.9 and 1.6 mm (p = .03) in lateral cheeks were measured in middle and old age groups. CONCLUSION: A steady and significant decline in the soft tissue thickness was noted at all measured sites in men over time. These findings are in contrast to our recently study in women showing dramatic loss of soft tissue between the ages of 30 and 60 with no significant differences between the middle and old-aged groups. These results have implications for volume correction and maintenance of a youthful appearance in the aging male face. PMID- 25111353 TI - Trilobed flap for inferior-medial alar defect. PMID- 25111354 TI - Commentary on the Trilobed flap for inferior-medial alar defect. PMID- 25111355 TI - Response to onychodystrophy treated using fractional carbon dioxide laser therapy and topical steroids. PMID- 25111356 TI - An important mimicker: plaque-type syringoma mistakenly diagnosed as microcystic adnexal carcinoma. PMID- 25111357 TI - Chromophoric and dendritic phosphoramidites enable construction of functional dendrimers with exceptional brightness and water solubility. AB - The fluorescence brightness of a molecular probe determines whether it can be effectively measured and its water solubility dictates if it can be applied in real-world biological systems. However, molecules brighter than the most efficient fluorescent dyes or particles brighter than quantum dots are hard to come by, especially when they must also be soluble in water. In this report, chromophoric phosphoramidites are used in a solid-state synthesis to construct functional dendrimers. When highly twisted chromophores are chosen and the proper spacers and dendrons are introduced, the resultant dendrimers emit exceptionally bright fluorescence. Chromophores, spacers, and dendrons are stitched together by efficient phosphoramidite reagents, which afford high-yield water-soluble phosphodiester linkages after deprotection. The resulting water-soluble dendrimers are exceptionally bright. PMID- 25111358 TI - Geometric and redox flexibility of pyridine as a redox-active ligand that can reversibly accept one or two electrons. AB - A low-coordinate iron(I) species can reversibly reduce pyridine, either by one electron to give a new C-C bond, or by two electrons to give a pyridine-derived bridge with an unprecedented MU-eta(1):eta(3) binding mode. PMID- 25111359 TI - Bacterial imprinting at Pickering emulsion interfaces. AB - The tendency of bacteria to assemble at oil-water interfaces can be utilized to create microbial recognition sites on the surface of polymer beads. In this work, two different groups of bacteria were first treated with acryloyl-functionalized chitosan and then used to stabilize an oil-in-water emulsion composed of cross linking monomers that were dispersed in aqueous buffer. Polymerization of the oil phase followed by removal of the bacterial template resulted in well-defined polymer beads bearing bacterial imprints. Chemical passivation of chitosan and cell displacement assays indicate that the bacterial recognition on the polymer beads was dependent on the nature of the pre-polymer and the target bacteria. The functional materials for microbial recognition show great potential for constructing cell-cell communication networks, biosensors, and new platforms for testing antibiotic drugs. PMID- 25111360 TI - Theoretical exploration of the potential and force acting on one electron within a molecule. AB - The potential and force acting on one electron within a molecule (PAEM and FAEM) have been investigated and analyzed. The PAEM, defined as the interaction energy on one electron provided by all the nuclei and the remaining electrons in a molecule, can be precisely expressed and calculated by ab initio method and our in-house program. Although the analysis of the scalar function PAEM is similar to that of the molecular electron density in the Bader's AIM theory, the former is distinct from the latter mainly in three points: (a) The minus gradient of the PAEM is the force acting on one electron within a molecule (FAEM). (b) The bond center is defined in terms of the features of FAEM and PAEM between two bonded atoms, and it is a two-dimensional attractive center whereas a nucleus is a three dimensional attractive source for electrons. We have calculated the physical quantities of one electron at the bond center, such as Dpb, the Hessian matrix, and its eigenvalues. Interestingly, it is found that the force constant and frequency of the electron interflow around the bond center are well correlated with those corresponding quantities for the nuclear vibration which relate to the bond strength, for some series of diatomic molecules. (c) The bond center locates at a different point from that of the critical point of the electron density in the Bader's AIM theory, which will lead to different partitioning of the molecular space into the atomic regions. PMID- 25111361 TI - [Conflicting Rules and Incentives for Health Promotion and Prevention in the German Statutory Health Insurance (GKV)]. AB - OBJECTIVES: This study examines what role the German statutory health insurance (GKV) has in health promotion and prevention, if regulations and incentives are consistent, and if the politically-intended strengthening of prevention has been achieved. METHODS: We compiled the regulations and incentives of the German Sozialgesetzbuch V as the legal basis for health promotion and prevention of the GKV and studied their effects and interactions. Using annual financial reports of GKV we determined how the spending in prevention overall and in specific fields of prevention has -developed. RESULTS: The responsibilities of the GKV in health promotion and prevention lack a clear scientific foundation. Regulations have been incrementally added following changing ideas in prevention and health promotion policies. Currently, different norms and a variety of incentives lead to inconsistent and conflicting aims. Only 2% of all expenditures of the GKV are for health promotion and prevention, mainly spent for medical measures like preventive medical check-ups or vaccination. While spending of the GKV in general is rising, expenditures for prevention have decreased since 2009. CONCLUSIONS: There is a need to harmonise the different regulations in health promotion and prevention and to correct currently inconsistent incentives in the GKV. Given the similar evidence base there seems to be no reason why responsibilities for health promotion and primary, secondary or tertiary prevention should be regulated by different normative constructs. Incentives should account for the different aims of health insurers and their members. Financial incentives to increase spending in prevention may be particularly effective when there is no short-term financial interest for the health insurer. PMID- 25111362 TI - [Which Factors Affect Weight Maintenance? A Qualitative Study with Adolescents and their Parents who have Completed a Ten-months Intervention]. AB - BACKGROUND: The alarming increase in the prevalence of childhood obesity is recognised as a major public health concern. Currently, structured multi-modal therapy programmes present the gold standard of therapy strategies for obese children and adolescents. However, effects of these treatments are still a matter of discussion. Failure to isolate and understand the external and internal factors contributing to successful, long-term weight reduction may well be contributing to the ineffectiveness of current treatment interventions. OBJECTIVE: A qualitative approach was chosen in order to identify subjectively perceived resources and barriers to weight maintenance after previous weight reduction. The research question focused on how these resources and barriers affect success of participants. Additionally the question arose as to how and to what extent parents should and could be involved in the therapy process. The results can deliver important starting points for the development of therapy programmes and future research. METHOD: 7 participants of a weight reduction and maintenance programme and 7 of their parents were interviewed on their personal experiences during and after the treatment. The interviews were analysed based on the qualitative content analysis. RESULTS: Continuous motivation, especially after the initial weight reduction phase, was identified as the strongest predictor of successful weight maintenance. Successful weight maintainers generally showed characteristics of higher self-efficacy, internal motivation concerning physical activity and flexible self-control concerning food intake. Unsuccessful weight gainers stated a lack of motivation concerning physical activity and lost control over their eating habits. Concerning the role of parents in the therapy process, the results show that higher parental involvement does not predict greater success. The general relationship between parents and their children seems to be more significant, especially concerning the issues of responsibility. CONCLUSION: It is disputable to what extent the post treatment intervention contributed to the development of intrinsic motivation. More attention should be paid to the age (children or adolescents) of participants of therapy programmes, especially concerning the involvement of parents. It is assumed that general aspects of education should be discussed with parents. PMID- 25111363 TI - Redifferentiation of dedifferentiated chondrocytes in a novel three-dimensional microcavitary hydrogel. AB - Although chondrocytes exist in native cartilage all over the body, it is still a challenge to use them as therapeutic cells for cartilage tissue engineering (TE) because of their easy dedifferentiation in in vitro culture. An improved culture system to maintain the characteristics of chondrocytes or recover their chondrocytic phenotype should be developed. In this study, we have set up an innovative microcavitary alginate hydrogel in an easy way. We compared this culture system with the conventional hydrogel and found that the microcavitary hydrogel exhibited outstanding superiorities in helping the dedifferentiated chondrocytes recover the capability for synthesizing cartilaginous extracellular matrix. In addition, we explored the correlation between chondrocyte redifferentiation in microcavitary hydrogels and changes in p38 and Erk1/2 activity. Our findings indicated that this microcavitary hydrogel would be a promising culture system to provide sufficient competent cells for cartilage regeneration and TE. PMID- 25111364 TI - High prevalence of antineuronal antibodies in Tunisian psychiatric inpatients. AB - The authors aimed to determine the prevalence of antineuronal antibodies in 103 psychiatric inpatients and 41 control subjects with no history of malignancies or neurological disorders. All sera were tested by indirect immunofluorescence and positive sera by immunoblot. Using immunofluorescence, antineuronal nuclear autoantibodies were detected in 20 patients and none of the control subjects, and antibodies reacted with the cytoplasm of Purkinje cells in six patients and two control subjects. The immunoblot confirmed well-characterized antineuronal antibodies only in five patients: two had anti-Ri and three had anti-Yo antibodies. After a follow-up of 5 years, none of these patients developed neurological disorder or malignancy. PMID- 25111365 TI - Patients with mental-physical multimorbidity: do not let them fall by the wayside. PMID- 25111366 TI - Highly stable dye-sensitized solar cells based on novel 1,2,3-triazolium ionic liquids. AB - We describe the design and synthesis of novel low viscosity bicyclic 1,2,3 triazolium ionic liquids. These new salts are applied as nonvolatile electrolytes in dye-sensitized solar cells, affording efficiencies up to 7.07% at low light intensities, and 6.00% when illuminated at 100 mW cm(-2). The devices are highly stable, retaining ca. 90% of their initial performance even after 1000 h of sun testing at 60 degrees C. The results obtained with these new ionic liquids compare very favorably to benchmark ionic liquid-based devices and illustrate the potential of the triazolium family of salts to compete with their imidazolium counterparts. PMID- 25111367 TI - Characterization of rubella virus genotypes among pregnant women in northern Vietnam, 2011-2013. AB - Rubella virus (RV) infection is an unresolved clinical complication that affects children in developing countries including Vietnam. RV infection during the first trimester of pregnancy causes severe birth defects known as congenital rubella syndrome. This study reports on the genomic characterization of RV strains circulating in northern Vietnam during 2011-2013. RV-IgM positive amniotic fluid specimens were collected from 38 women from northern Vietnam who presented with clinical rubella at the National Hospital of Obstetrics and Gynecology in Hanoi, Vietnam. The RV genes were determined by nested PCR with primers amplifying the 739-nucleotide coding region of the E1 gene. The sequences from the amplified DNA fragments were phylogenetically analyzed and compared to reference RV strains. Seventeen out of 38 samples are positive for RV detecting. All new RV isolates are clustered to genotype 2B. Eighteen amino acid mutations were found in the T and B cell epitopes. These results suggest that genotype 2B RV strains frequently circulate in northern Vietnam. These data describe the RV genotype in Vietnam with the aim of improving maternal and child health in this country. PMID- 25111368 TI - Specific behavioral comorbidity in a large sample of children with functional incontinence: Report of 1,001 cases. AB - AIMS: Psychological comorbidity among children with functional incontinence is high: 20-30% of children with nocturnal enuresis (NE), 20-40% of those with daytime urinary incontinence (DUI) and 30-50% of those with fecal incontinence (FI) have clinically relevant comorbid disorders. The aim of this study was to analyze specific comorbid behavioral symptoms for different subtypes of incontinence in a large group of children. METHODS: All 1,001 consecutive children and adolescents (67.5% boys) with a mean age of 8.5 years presented at a tertiary outpatient department between 2004 and 2011 were examined with a full pediatric and child psychiatric assessment. Prevalence of different subforms of incontinence and associated behavioral symptoms were analyzed. The internalizing, externalizing, and total problem scores of the Child Behavior Checklist (CBCL) were evaluated. RESULTS: Of all children, 70.1% (702 children) had NE, 36.1% (361 children) had DUI, and 36.8% (368 children) were affected by FI. More than 43% of all children had clinically relevant psychological symptoms (CBCL total score, cut-off at 90th percentile). Children with non-retentive FI had highest rates of clinically relevant psychological symptoms (58.8%). Children with combined subtypes of incontinence (any combination of NE, DUI, and FI) were more affected by psychological comorbidities than children with isolated subtypes (NE or DUI or FI). CONCLUSIONS: Children with incontinence have high rates of comorbid behavioral symptoms-three to six times higher than norms. Especially children with FI and combined subtypes of incontinence were affected. As behavioral symptoms and disorders will interfere with incontinence treatment, a general screening is recommended. PMID- 25111369 TI - Neonatal lung function and therapeutics. AB - Respiratory diseases are increasingly recognized as having their origins during perinatal and early postnatal lung development, a time of significant adaptation to large changes in redox conditions as well as to mechanical forces. This Forum of the journal presents a Forum highlighting studies of the interplay between reactive oxygen/nitrogen species and the systems that have evolved to degrade them or exploit them, as well as the cellular repair processes which respond to early life redox stress in the lung. This group of authors suggests new understandings of these events that may point the way to improved therapeutic approaches. PMID- 25111371 TI - Randomized clinical trials and observational studies are more often alike than unlike. PMID- 25111372 TI - Copper(I) bromide catalyzed arylation of cyclic enamides and naphthyl-1 acetamides using diaryliodonium salts. AB - Copper(I) bromide catalyzed direct C-H arylation of cyclic enamides was achieved using diaryliodonium salts in the absence of base/additive at ambient temperature with high yields. A biologically active dihydro[a]benzocarbazole scaffold was synthesized using the established protocol. The scope of the current methodology was further extended for the synthesis of C4-, C7-aryl-substituted 1-naphthyl acetamides in good yields. PMID- 25111370 TI - Diurnal floc generation from neuston biofilms in two contrasting freshwater lakes. AB - Selective adaptation of biofilm-forming bacteria to the nutrient-rich but environmentally challenging conditions of the surface microlayer (SML) or neuston layer was evident in littoral regions of two physically and geochemically contrasting freshwater lakes. SML bacterial communities (bacterioneuston) in these systems were depleted in Actinobacteria, enriched in either Betaproteobacteria or Gammaproteobacteria, and either unicellular Cyanobacteria were absent or microbial mat forming Cyanobacteria enriched relative to communities in the underlying shallow water column (0.5 m depth). Consistent with the occurrence of biofilm-hosted, geochemically distinct microhabitats, As-, Fe-, and S-metabolizing bacteria including anaerobic taxa were detected only in the SML in both systems. Over diurnal time scales, higher wind speeds resulted in the generation of floc from SML biofilms, identifying a transport mechanism entraining SML accumulated microorganisms, nutrients, and contaminants into the underlying water column. The energy regime experienced by the SML was more important to floc generation as larger flocs were more abundant in the larger, oligotrophic lake (higher relative energy regime) compared to the sheltered, smaller lake, despite relatively higher concentrations of bacteria, organic carbon, Fe, and PO4(3-) in the latter system. PMID- 25111373 TI - A novel angiotensin-I converting enzyme (ACE) inhibitory peptide from gastrointestinal protease hydrolysate of silkworm pupa (Bombyx mori) protein: Biochemical characterization and molecular docking study. AB - Silkworm pupa (Bombyx mori) protein was hydrolyzed using gastrointestinal endopeptidases (pepsin, trypsin and alpha-chymotrypsin). Then, the hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and RP-HPLC. A novel ACE inhibitory peptide, Ala-Ser-Leu, with the IC50 value of 102.15MUM, was identified by IT-MS/MS. This is the first report of Ala-Ser-Leu from natural protein. Lineweaver-Burk plots suggest that the peptide is a competitive inhibitor against ACE. The molecular docking studies revealed that the ACE inhibition of Ala-Ser-Leu is mainly attributed to forming very strong hydrogen bonds with the S1 pocket (Ala354) and the S2 pocket (Gln281 and His353). The results indicate that silkworm pupa (B. mori) protein or its gastrointestinal protease hydrolysate could be used as a functional ingredient in auxiliary therapeutic foods against hypertension. PMID- 25111374 TI - Downregulation of natriuretic peptide system and increased steroidogenesis in rat polycystic ovary. AB - Atrial natriuretic peptide (ANP) is known to regulate ovarian functions, such as follicular growth and steroid hormone production. The aim of the present study was to investigate the natriuretic peptide system in a rat model of chronic anovulation, the rat polycystic ovary. Adult female Wistar rats received a single subcutaneous injection of 2mg estradiol valerate to induce polycystic ovaries, while the control group received vehicle injection. Two months later, their ovaries were quickly removed and analyzed. Polycystic ovaries exhibited marked elevation of testosterone and estradiol levels compared to control ovaries. The levels of ANP and the expression of ANP mRNA were highly reduced in the polycystic ovaries compared to controls. By immunohistochemistry, polycystic ovaries showed weaker ANP staining in stroma, theca cells and oocytes compared to controls. Polycystic ovaries also had increased activity of neutral endopeptidase, the main proteolytic enzyme that degrades natriuretic peptides. ANP receptor C mRNA was reduced and ANP binding to this receptor was absent in polycystic ovaries. Collectively, these results indicate a downregulation of the natriuretic peptide system in rat polycystic ovary, an established experimental model of anovulation with high ovarian testosterone and estradiol levels. Together with previous evidence demonstrating that ANP inhibits ovarian steroidogenesis, these findings suggest that low ovarian ANP levels may contribute to the abnormal steroid hormone balance in polycystic ovaries. PMID- 25111375 TI - Explaining educational disparities in adiposity: the role of neighborhood environments. AB - OBJECTIVE: To examine the extent to which characteristics of the neighborhood built environment explain the association between adiposity and educational qualifications in Australian women. METHODS: A community sample of 1,819 women (aged 18-66) from the Melbourne SESAW study provided information regarding their body mass index (BMI) and level of education. Objective measures of participants' residential neighborhood built environments were obtained using a Geographic Information System. RESULTS: Compared with women with a high school degree or above, women who did not complete high school had higher average BMI, which was partially explained by lower density of sports facilities and living less proximally to the coastline and to supermarkets. In a multiple mediator model, which explained 16.6% of the educational disparity in BMI, the number of sports facilities and presence of the coastline within 2 km of participants' homes were significant mediators of the observed socioeconomic disparity in BMI. CONCLUSIONS: The residential neighborhood environment may help to explain socioeconomic patterning of overweight and obesity in Australian women. These results provide further support for considering the built environment in obesity prevention initiatives, suggesting a potential role in decreasing social inequalities in obesity. PMID- 25111376 TI - Down-modulation of Bcl-2 sensitizes PTEN-mutated prostate cancer cells to starvation and taxanes. AB - BACKGROUND: The critical role of PTEN in regulating the PI3K/Akt/mTOR signaling pathway raises the possibility that targeting downstream effectors of the PI3K pathway, such as Bcl-2, might be an effective anti-proliferative strategy for PTEN-deficient prostate cancer cells. METHODS: Four prostate cancer cell lines (LNCaP, PC3, DU145, 22Rv1) were assayed for their levels of total Akt and Ser473 phosphorylated Akt (p-Akt) by Western Blotting; their growth rates and sensitivity to different doses of paclitaxel were determined by cell counts after Trypan Blue dye exclusion assay. Cells were subjected to different combinations of starvation (growth factors and/or aminoacids withdrawal), paclitaxel treatment and Bcl-2 silencing by siRNA. Cell viability was evaluated by Trypan Blue dye exclusion assay, Propidium Iodide (PI) and Annexin-V/PI staining. RESULTS: We assessed the sensitivity of different prostate cancer cell lines to starvation and we observed a differential response correlated to the levels of Akt activation. The four prostate cancer cell lines also showed different sensitivity to taxol treatments; LNCaP and 22Rv1 cells were more resistant to paclitaxel than DU145 and PC3 cells. Combining taxol with growth factors and aminoacids deprivation leaded to a more than additive reduction of cell viability compared to single treatments in PTEN-mutant LNCaP cells. Down-modulation of anti apoptotic Bcl-2 protein by siRNA sensitized LNCaP cells to taxanes and starvation induced cell death. CONCLUSIONS: Silencing Bcl-2 in PTEN-mutated prostate cancer cells enhances the apoptotic effects of combined starvation and taxol treatments, indicating that inhibition of Bcl-2 may be of significant value in PTEN-mutant tumor therapy. PMID- 25111377 TI - Oncofetal signaling as a target for cancer therapy. PMID- 25111379 TI - Evidence-based psychological interventions and the common factors approach: the beginnings of a rapprochement? AB - Laska, Gurman, and Wampold (2014, pp. 467-481) argue that common factors (CFs) have largely been ignored by clinical researchers developing research-based interventions but that CFs are primarily responsible for therapeutic change. On the contrary, many clinical researchers developing empirically supported treatments have been studying the contribution of these factors for decades. What has been demonstrated is that these factors are contributory, but are not sufficient to produce maximum effects and their impact differs greatly from disorder to disorder. But we also take note of a change of tone and perhaps substance from these authors on the contribution of CFs to evidence-based psychological interventions, and reflect on recent changes in our own views both of which may reduce differences in our respective positions. PMID- 25111378 TI - Blockade of IL-36 receptor signaling does not prevent from TNF-induced arthritis. AB - INTRODUCTION: Interleukin (IL)-36alpha is a newly described member of the IL-1 cytokine family with a known inflammatory and pathogenic function in psoriasis. Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36alpha and its antagonist IL-36Ra are expressed in synovial tissue of arthritis patients. Furthermore, IL-36alpha induces MAP-kinase and NFkappaB signaling in human synovial fibroblasts with subsequent expression and secretion of pro inflammatory cytokines. METHODS: To understand the pathomechanism of IL-36 dependent inflammation, we investigated the biological impact of IL-36alpha signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL 36alpha was tested in murine and human osteoclast assays. RESULTS: Diseased mice showed an increased expression of IL-36R and IL-36alpha in inflamed knee joints compared to wildtype controls. However, preventively treating mice with an IL-36R blocking antibody led to no changes in clinical onset and pattern of disease. Furthermore, blockade of IL-36 signaling did not change histological signs of TNF induced arthritis. Additionally, no alteration on bone homeostasis was observed in ex vivo murine and human osteoclast differentiation assays. CONCLUSION: Thus we conclude that IL-36alpha does not affect the development of inflammatory arthritis. PMID- 25111380 TI - Use of relational strategies to repair alliance ruptures: How responsive supervisors train responsive psychotherapists. AB - Inasmuch as therapist responsiveness is the crucial ingredient in psychotherapy success, teaching supervisees to be optimally responsive to their clients is the primary function of supervision. Responsive supervision is particularly critical when a trainee experiences a faltering or problematic working alliance with a client. In this article, I describe and illustrate how supervisors can work responsively, both explicitly (through instruction) and implicitly (through modeling) when their supervisees report a serious alliance rupture. Next, I illustrate, with the same case example, how quickly ruptures in the therapeutic alliance can lead to ruptures in the supervisory alliance when the supervisor is not sufficiently responsive to the trainee's needs and, instead, relies exclusively on case management. Throughout the article, I discuss how the construct of responsiveness fits within the substantial body of theory and research on relational processes in supervision. PMID- 25111381 TI - Common factors are not so common and specific factors are not so specified: toward an inclusive integration of psychotherapy research. AB - The dichotomy between what has been termed empirically supported treatments (EST) and common factors (CF) is false and counterproductive. Neither has a monopoly on empirical truth. The term nonspecific is unproductive and misleading. Specified versus nonspecified is more empirically correct. Assumptions of the EST and CF approaches are questionable. Common factors (both currently specified and not so specified) are reviewed. These include the therapeutic relationship, expectancies, attributions for therapeutic success, exposure, and mastery. Far from maximizing therapeutic success, the CF EST dichotomy and its resulting theoretical squabbles result in weaker outcomes than would be the case if empirical results were taken seriously, and factors shown to be effective (both specified and nonspecified) were systematically investigated and integrated so as to create maximally effective treatments. PMID- 25111382 TI - Crystal structures of PRK1 in complex with the clinical compounds lestaurtinib and tofacitinib reveal ligand induced conformational changes. AB - Protein kinase C related kinase 1 (PRK1) is a component of Rho-GTPase, androgen receptor, histone demethylase and histone deacetylase signaling pathways implicated in prostate and ovarian cancer. Herein we describe the crystal structure of PRK1 in apo form, and also in complex with a panel of literature inhibitors including the clinical candidates lestaurtinib and tofacitinib, as well as the staurosporine analog Ro-31-8220. PRK1 is a member of the AGC-kinase class, and as such exhibits the characteristic regulatory sequence at the C terminus of the catalytic domain--the 'C-tail'. The C-tail fully encircles the catalytic domain placing a phenylalanine in the ATP-binding site. Our inhibitor structures include examples of molecules which both interact with, and displace the C-tail from the active site. This information may assist in the design of inhibitors targeting both PRK and other members of the AGC kinase family. PMID- 25111383 TI - 18F-glutathione conjugate as a PET tracer for imaging tumors that overexpress L PGDS enzyme. AB - Lipocalin-type prostaglandin D synthase (L-PGDS) has been correlated with the progression of neurological disorders. The present study aimed at evaluating the imaging potency of a glutathione conjugate of fluorine-18-labeled fluorobutyl ethacrynic amide ([18F]FBuEA-GS) for brain tumors. Preparation of [18F]FBuEA-GS has been modified from the -4-tosylate derivative via radiofluorination in 5% radiochemical yield. The mixture of nonradioactive FBuEA-GS derived from a parallel preparation has be resolved to two isomers in a ratio of 9:1 using analytic chiral reversed phase high performance liquid chromatography (RP-HPLC). The two fluorine-18-labeled isomers purified through nonchiral semipreparative RP HPLC as a mixture were studied by assessing the binding affinity toward L-PGDS through a gel filtration HPLC, by analyzing radiotracer accumulation in C6 glioma cells, and by evaluating the imaging of radiotracer in a C6 glioma rat with positron emission tomography. The inhibition percentage of the production of PGD2 from PGH2 at the presence of 200 uM of FBuEA-GS and 4-Dibenzo[a,d]cyclohepten-5 ylidene-1-[4-(2H-tetrazol-5-yl)butyl]piperidine (AT-56) were 74.1 +/- 4.8% and 97.6 +/- 16.0%, respectively. [18F]FBuEA-GS bound L-PGDS (16.3-21.7%) but not the isoform, microsomal prostaglandin E synthase 1. No binding to GST-alpha and GST pi was observed. The binding strength between [18F]FBuEA-GS and L-PGDS has been evaluated using analytic gel filtration HPLC at the presence of various concentrations of the cold competitor FBuEA-GS. The contrasted images indicated that the radiotracer accumulation in tumor lesions is probably related to the overexpression of L-PGDS. PMID- 25111384 TI - Enhanced anti-tumor effect of zoledronic acid combined with temozolomide against human malignant glioma cell expressing O6-methylguanine DNA methyltransferase. AB - Temozolomide (TMZ), a DNA methylating agent, is widely used in the adjuvant treatment of malignant gliomas. O6-methylguanine-DNA methyltranferase (MGMT), a DNA repair enzyme, is frequently discussed as the main factor that limits the efficacy of TMZ. Zoledronic acid (ZOL), which is clinically applied to treat cancer-induced bone diseases, appears to possess direct anti-tumor activity through apoptosis induction by inhibiting mevalonate pathway and prenylation of intracellular small G proteins. In this study, we evaluated whether ZOL can be effectively used as an adjuvant to TMZ in human malignant glioma cells that express MGMT. Malignant glioma cell lines, in which the expression of MGMT was detected, did not exhibit growth inhibition by TMZ even at a longer exposure. However, combination experiment of TMZ plus ZOL revealed that a supra-additive effect resulted in a significant decrease in cell growth. In combined TMZ/ZOL treatment, an increased apoptotic rate was apparent and significant activation of caspase-3 and cleavage of poly-(ADP-ribose) polymerase were observed compared with each single drug exposure. There were decreased amounts of Ras-GTP, MAPK and Akt phosphorylation and MGMT expression in the ZOL-treated cells. Subcutanous xenograft models showed significant decrease of tumor growth with combined TMZ/ZOL treatment. These results suggest that ZOL efficaciously inhibits activity of Ras in malignant glioma cells and potentiates TMZ-mediated cytotoxicity, inducing growth inhibition and apoptosis of malignant glioma cells that express MGMT and resistant to TMZ. Based on this work, combination of TMZ with ZOL might be a potential therapy in malignant gliomas that receive less therapeutic effects of TMZ due to cell resistance. PMID- 25111385 TI - Bipolar vaporization, resection, and enucleation versus open prostatectomy: optimal treatment alternatives in large prostate cases? AB - OBJECTIVES: The study compared the transurethral resection in saline (TURis), transurethral vaporization in saline (TUVis), bipolar plasma enucleation of the prostate (BPEP), and open prostatectomy (OP) in a single-center, prospective, randomized controlled clinical setting exclusively involving large prostate patients. PATIENTS AND METHODS: During a 41/2 year enrollment period, 320 cases of prostate volume over 80 mL, maximum flow rate (Qmax) below 10 mL/second, International Prostate Symptom Score (IPSS) over 19, or urinary retention were included in the trial and equally randomized in the four study arms. Patients were assessed preoperatively as well as at the 1-, 3-, 6-, and 12-month follow-up checkups using the IPSS, quality of life (QoL) score, Qmax, postvoiding residual urinary volume (PVR), and prostate-specific antigen (PSA). RESULTS: Similar preoperative parameters were established in the four series. OP and BPEP were characterized by resembling operating times, while TURis and TUVis displayed prolonged surgical durations. TURis emphasized a substantially decreased mean resected tissue weight. TUVis showed the lowest mean hemoglobin level drop, followed by TURis and BPEP (equivalent results) and finally OP (highest bleeding). OP described the longest mean catheterization period and hospital stay, followed by TURis, and afterward by TUVis and BPEP (similar data). During the follow-up period, statistically equivalent IPSS, QoL, Qmax, and PVR outcomes were established for OP, BPEP, and TURis. TUVis displayed significantly smaller Qmax improvements, but similar other functional features. Significantly lower mean PSA levels were determined secondary to OP and BPEP when compared to bipolar resection and subsequently to vaporization. CONCLUSIONS: OP and BPEP emphasized the highest surgical efficiency (prolonged postoperative recovery for OP), while TUVis displayed the lowest hemorrhagic risks. On the medium term, generally resembling functional outcomes were determined for the four techniques, with significantly decreased mean PSA values secondary to OP and BPEP. PMID- 25111386 TI - Electron spin resonance of nitrogen-vacancy defects embedded in single nanodiamonds in an ABEL trap. AB - Room temperature optically detected magnetic resonance of a single quantum object with nanoscale position control is an outstanding challenge in many areas, particularly in the life sciences. We introduce a novel approach to control the nitrogen-vacancy (NV) centers hosted in a single fluorescent nanodiamond (FND) for which an anti-Brownian electrokinetic trap (ABEL) performs the position control and an integrated radiofrequency (RF) circuit provides enhanced magnetic flux density for ensemble spin-state control simultaneously. We demonstrate static magnetic field sensing in platforms compatible with ABEL trap. With the advances in the synthesis and functionalization of stable arbitrarily small FNDs, we foresee the use of our device for the trapping and manipulation of single molecular-sized FNDs in aqueous solution. PMID- 25111387 TI - Methylation marker analysis and HPV16/18 genotyping in high-risk HPV positive self-sampled specimens to identify women with high grade CIN or cervical cancer. AB - OBJECTIVES: Methylation marker analysis using bi-marker panel MAL/miR-124-2 is a promising triage test for identifying cervical (pre)cancer in high-risk human papillomavirus (hrHPV) positive women. Bi-marker panel MAL/miR-124-2 can be applied directly on self-sampled cervico-vaginal material and its sensitivity is non-inferior to that of cytology, yet at the cost of more colposcopy referrals. Our objective was to increase specificity of MAL/miR-124-2 methylation analysis by varying the assay thresholds and adding HPV16/18 genotyping. METHODS: 1019 hrHPV-positive women were selected from a randomized controlled self-sampling trial (PROHTECT-3; 33-63 years, n=46,001) and nine triage strategies with methylation testing of MAL/miR-124-2 and HPV16/18 genotyping were evaluated. The methylation assay threshold was set at four different predefined levels which correspond with clinical specificities for end-point cervical intra-epithelial grade 3 or worse (CIN3+) of 50%, 60%, 70%, and 80%. RESULTS: The CIN3+ sensitivity of methylation analysis decreased (73.5 to 44.9%) while specificity increased (47.2 to 83.4%) when increasing the assay threshold. CIN3+ sensitivity and specificity of HPV16/18 genotyping were 68.0% and 65.6%, respectively. Combined methylation analysis at threshold-80 and HPV16/18 genotyping yielded similar CIN3+ sensitivity as that of methylation only at threshold-50 (77.6%) with an increased specificity (54.8%). CONCLUSIONS: Combined triage by MAL/miR 124-2 methylation analysis with threshold-80 and HPV16/18 genotyping reaches high CIN3+ sensitivity with increased specificity to identify women with cervical (pre)cancer among HPV self-sample positive women. The combined strategy is attractive as it is fully molecular and identifies women at the highest risk of cervical (pre)cancer because of strongly elevated methylation levels and/or HPV16/18 positivity. PMID- 25111389 TI - Thermoresponsive poly(N-isopropylacrylamide)/graphene/Au nanocomposite hydrogel for water treatment by a laser-assisted approach. AB - The thermoresponsive poly(N-isopropylacrylamide)/graphene/Au multicomponent hydrogel is prepared by the simultaneous in-situ formation of Au nanoparticles and the reduction of graphene oxide, assisted by NIR laser irradiation of a prefabricated PNIPAM/GO hydrogel with auric acid precursor, showing great potential for water treatment owing to the excellent photothermal effect. PMID- 25111391 TI - Treatment of Mycobacterium tuberculosis infection: time to get a move on? PMID- 25111390 TI - Plasma levels of microRNA-499 provide an early indication of perioperative myocardial infarction in coronary artery bypass graft patients. AB - BACKGROUND: Recent studies indicated that microRNAs (miRNAs, miRs) were important for many biological and pathological processes, and they might be potential biomarkers for cardiovascular diseases. The present study aims to determine the release patterns of miRNAs in cardiac surgery and to analyze the ability of miRs to provide early prediction of perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft (CABG) surgery. METHODOLOGY/PRINCIPAL FINDINGS: Thirty on-pump CABG patients were recruited in this study; and miR-499, miR-133a and miR-133b, cardiac troponin I (cTnI) were selected for measurement. Serial plasma samples were collected at seven perioperative time points (preoperatively, and 1, 3, 6, 12, 24, and 48 hours after declamping) and were tested for cTnI and miRs levels. Importantly, miR levels peaked as early as 1-3 hours, whereas cTnI levels peaked at 6 hours after declamping. Peak plasma concentrations of miRs correlated significantly with cTnI (miR-499, r = 0.583, P = 0.001; miR-133a, r = 0.514, P = 0.006; miR-133b, r = 0.437, P = 0.05), indicating the degree of myocardial damage. In addition, 30 off pump CABG patients were recruited; miR-499 and miR-133a levels were tested, which were significantly lower in off-pump group than in on-pump group. A prospective cohort of CABG patients (n = 120) was recruited to study the predictive power of miRs for PMI. The diagnosis of PMI strictly adhered to the principles of universal definition of myocardial infarction. The data analysis revealed that miR-499 had higher sensitivity and specificity than cTnI, and indicated that miR 499 could be an independent risk factor for PMI. CONCLUSION: Our results demonstrate that circulating miR-499 is a novel, early biomarker for identifying perioperative myocardial infarction in cardiac surgery. PMID- 25111392 TI - Microbial community structure of relict niter-beds previously used for saltpeter production. AB - From the 16th to the 18th centuries in Japan, saltpeter was produced using a biological niter-bed process and was formed under the floor of gassho-style houses in the historic villages of Shirakawa-go and Gokayama, which are classified as United Nations Educational, Scientific and Cultural Organization (UNESCO) World Heritage Sites. The relict niter-beds are now conserved in the underfloor space of gassho-style houses, where they are isolated from destabilizing environmental factors and retain the ability to produce nitrate. However, little is known about the nitrifying microbes in such relict niter-bed ecosystems. In this study, the microbial community structures within nine relict niter-bed soils were investigated using 454 pyrotag analysis targeting the 16S rRNA gene and the bacterial and archaeal ammonia monooxygenase gene (amoA). The 16S rRNA gene pyrotag analysis showed that members of the phyla Proteobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, Firmicutes, Gemmatimonadetes, and Planctomycetes were major microbial constituents, and principal coordinate analysis showed that the NO3-, Cl-, K+, and Na+ contents were potential determinants of the structures of entire microbial communities in relict niter bed soils. The bacterial and archaeal amoA libraries indicated that members of the Nitrosospira-type ammonia-oxidizing bacteria (AOB) and "Ca. Nitrososphaera" type ammonia-oxidizing archaea (AOA), respectively, predominated in relict niter bed soils. In addition, soil pH and organic carbon content were important factors for the ecological niche of AOB and AOA in relict niter-bed soil ecosystems. PMID- 25111393 TI - Population genomics of the fission yeast Schizosaccharomyces pombe. AB - The fission yeast Schizosaccharomyces pombe has been widely used as a model eukaryote to study a diverse range of biological processes. However, population genetic studies of this species have been limited to date, and we know very little about the evolutionary processes and selective pressures that are shaping its genome. Here, we sequenced the genomes of 32 worldwide S. pombe strains and examined the pattern of polymorphisms across their genomes. In addition to introns and untranslated regions (UTRs), intergenic regions also exhibited lower levels of nucleotide diversity than synonymous sites, suggesting that a considerable amount of noncoding DNA is under selective constraint and thus likely to be functional. A number of genomic regions showed a reduction of nucleotide diversity probably caused by selective sweeps. We also identified a region close to the end of chromosome 3 where an extremely high level of divergence was observed between 5 of the 32 strains and the remain 27, possibly due to introgression, strong positive selection, or that region being responsible for reproductive isolation. Our study should serve as an important starting point in using a population genomics approach to further elucidate the biology of this important model organism. PMID- 25111394 TI - Nowcasting the spread of chikungunya virus in the Americas. AB - BACKGROUND: In December 2013, the first locally-acquired chikungunya virus (CHIKV) infections in the Americas were reported in the Caribbean. As of May 16, 55,992 cases had been reported and the outbreak was still spreading. Identification of newly affected locations is paramount to intervention activities, but challenging due to limitations of current data on the outbreak and on CHIKV transmission. We developed models to make probabilistic predictions of spread based on current data considering these limitations. METHODS AND FINDINGS: Branching process models capturing travel patterns, local infection prevalence, climate dependent transmission factors, and associated uncertainty estimates were developed to predict probable locations for the arrival of CHIKV infected travelers and for the initiation of local transmission. Many international cities and areas close to where transmission has already occurred were likely to have received infected travelers. Of the ten locations predicted to be the most likely locations for introduced CHIKV transmission in the first four months of the outbreak, eight had reported local cases by the end of April. Eight additional locations were likely to have had introduction leading to local transmission in April, but with substantial uncertainty. CONCLUSIONS: Branching process models can characterize the risk of CHIKV introduction and spread during the ongoing outbreak. Local transmission of CHIKV is currently likely in several Caribbean locations and possible, though uncertain, for other locations in the continental United States, Central America, and South America. This modeling framework may also be useful for other outbreaks where the risk of pathogen spread over heterogeneous transportation networks must be rapidly assessed on the basis of limited information. PMID- 25111396 TI - (Phenoxyimidazolyl-salicylaldimine)iron complexes: synthesis, properties and iron catalysed ethylene reactions. AB - The reaction of 2-{[2-(1H-imidazol-4-yl)-ethylimino]-methyl}-phenol (L1), 2,4-di tert-butyl-6-{[2-(1H-imidazol-4-yl)-ethylimino]-methyl}-phenol (L2) or 4-tert butyl-2-{[2-(1H-imidazol-4-yl)-ethylimino]-methyl}-phenol (L3) with iron(ii) precursors produced either iron(ii) or iron(iii) complexes, depending on the nature of the anions in the iron(ii) precursor and the ligand. When the anion is chloride and the ligand L1, the product is [(L1)2Fe][FeCl4] (1), but when the anion is triflate (OTf(-)) and the ligand is L2, the product is [(L2)2Fe][OTf]2 (2). With iron(ii) halides and tert-butyl groups on the phenoxy ligands L2 and L3, the iron(iii) complexes [(L2)FeX2] {where X = Cl (3), Br (4) and I = (5)} and [(L3)FeCl2] (6) were formed. Complexes 1-6 were characterised by a combination of elemental analyses, IR spectroscopy and mass spectrometry; and in selected cases (3 and 4) by single crystal X-ray crystallography. The crystal structures of 3 and 4 indicated that the iron(ii) precursors oxidised to iron(iii) in forming complexes 3-6; an observation that was corroborated by the magnetic properties and the (57)Fe Mossbauer spectra of 3 and 4. The iron(iii) complexes 3-6 were used as pre-catalysts for the oligomerisation and polymerisation of ethylene. Products of these ethylene reactions depended on the solvent used. In toluene ethylene oligomerised mainly to 1-butene and was followed by the 1-butene alkylating the solvent to form butyl-toluenes via a Friedel-Crafts alkylation reaction. In chlorobenzene, ethylene oligomerised mainly to a mixture of C4-C12 alkenes. Interestingly small amounts of butyl-chlorobenzenes and hexyl chlorobenzenes were also formed via a Friedel-Crafts alkylation with butenes and hexenes from the oligomerisation of ethylene. PMID- 25111395 TI - Diphenyl diselenide and sodium selenite associated with chemotherapy in experimental toxoplasmosis: influence on oxidant/antioxidant biomarkers and cytokine modulation. AB - SUMMARY The aim of this study was to assess the effect of sulfamethoxazole/trimethoprim (ST) supplemented with diphenyl diselenide and sodium selenite in experimental toxoplasmosis, on oxidant/antioxidant biomarkers and cytokine levels. Eighty-four BALB/c mice were divided in seven groups: group A (negative control), and groups B to G (infected). Blood and liver samples were collected on days 4 and 20 post infection (p.i.). Levels of thiobarbituric acid (TBA) reactive substances and advanced oxidation protein products (AOPP) were assessed in liver samples. Both biomarkers were significantly increased in infected groups on day 4 p.i., while they were reduced on day 20 p.i., compared with group A. Glutathione reductase (GR) activity significantly (P<0.01) increased on day 4 p.i., in group G, compared with group A. INF-gamma was significantly increased (P<0.001) in both periods, day 4 (groups B, C, F and G) and 20 p.i. (groups C, F and G). IL-10 significantly reduced (P<0.001) on day 4 p.i. in group B; however, in the same period, it was increased (P<0.001) in groups C and G, compared with group A. On day 20 p.i., IL-10 increased (P<0.001) in groups F and G. Therefore, our results highlighted that these forms of selenium, associated with the chemotherapy, were able to reduce lipid peroxidation and protein oxidation, providing a beneficial immunological balance between the production of pro- and anti-inflammatory cytokines. PMID- 25111397 TI - Rapidly developed neurosyphilis in a psoriasis patient under treatment with infliximab: a case report. PMID- 25111399 TI - National Association of Clinical Nurse Specialists news: Presidents message, June 2014. PMID- 25111398 TI - Thermoresponsive copolymer/SiO2 nanoparticles with dual functions of thermally controlled drug release and simultaneous carrier decomposition. AB - The preparation of thermoresponsive drug carriers with a self-destruction property is presented. These drug carriers were fabricated by incorporation of drug molecules and thermoresponsive copolymer, poly(N-isopropylacrylamide-co acrylamide), into silica nanoparticles in a one-pot preparation process. The enhanced drug release was primarily attributed to faster molecule diffusion resulting from the particle decomposition triggered by phase transformation of the copolymer upon the temperature change. The decomposition of the drug carriers into small fragments should benefit their fast excretion from the body. In addition, the resulting drug-loaded nanoparticles showed faster drug release in an acidic environment (pH 5) than in a neutral one. The controlled drug release of methylene blue and doxorubicin hydrochloride and the self-decomposition of the drug carriers were successfully characterized by using TEM, UV/Vis spectroscopy, and confocal microscopy. Together with the nontoxicity and excellent biocompatibility of the copolymer/SiO2 composite, the features of controlled drug release and simultaneous carrier self-destruction provided a promising opportunity for designing various novel drug-delivery systems. PMID- 25111400 TI - Clinical Nurse Specialists National Survey. PMID- 25111401 TI - The nurse's critical role in optimizing clinical documentation systems. PMID- 25111402 TI - The need for increased sex and gender-based analysis/subanalysis in nursing and medical research. PMID- 25111403 TI - Prescribing with an empty pharmacy: drug shortages update for the clinical nurse specialist. PMID- 25111404 TI - Transdermal fentanyl for cancer pain. PMID- 25111405 TI - Fundamentals of making a sale. PMID- 25111406 TI - Preoperative factors affecting the intraoperative core body temperature in abdominal surgery under general anesthesia: an observational cohort. AB - PURPOSE: The study was conducted to identify preoperative factors affecting the intraoperative core body temperature in abdominal surgery under general anesthesia. DESIGN: This study was performed through prospective descriptive research design. SETTING: The setting was a 1300-bed university hospital in Incheon, South Korea. SAMPLES: The sample consisted of 147 patients who had undergone elective abdominal surgery under general anesthesia. METHODS: Age, weight, and height were collected on a preoperative visit to general unit, and body mass index, body surface area, and total body fat were calculated. The basal preoperative core body temperature (CBT), preoperative blood pressure, and heart rate were measured. Core body temperature was again measured at 1, 2, and 3 hours following general anesthesia. RESULTS: Predictive factors of intraoperative hypothermia of less than 36 degrees C were preoperative CBT (beta = .44), weight (beta = .41), preoperative heart rate (beta = .20), and age (beta = -.13) at 1 hour after anesthesia (R = 0.658, F = 68.3, P < .001); preoperative CBT (beta = .33), weight (beta = .37), preoperative heart rate (beta = .22), and age (beta = .24) at 2 hours after anesthesia (R = 0.631, F = 60.8, P < .001); and age (beta = -.34), weight (beta = .36), preoperative CBT (beta = .30), and preoperative heart rate (beta = .20) at 3 hours after anesthesia (R = 0.665, F = 70.6, P < .001). CONCLUSION: Low preoperative body temperature and low weight seem to be risk factors of intraoperative hypothermia during 2 hours after anesthesia and advanced age and low weight at 3 hours following anesthesia. IMPLICATIONS: We recommend prewarming and intraoperative warming through forced air warming devices and covering a patient with a warm blanket during transportation. This procedure is necessary for the abdominal surgical patients of advanced age with low weight and duration of general anesthesia to last more than 1 hour. PMID- 25111407 TI - Modeling the complex activity of sickle cell and thalassemia specialist nurses in England. AB - OBJECTIVE: Specialist advanced practice nursing in hemoglobinopathies has a rich historical and descriptive literature. Subsequent work has shown that the role is valued by patients and families and also by other professionals. However, there is little empirical research on the complexity of activity of these services in terms of interventions offered. In addition, the work of clinical nurse specialists in England has been devalued through a perception of oversimplification. PURPOSE: The purpose of this study was to understand the complexity of expert nursing practice in sickle cell and thalassemia. DESIGN: The approach taken to modeling complexity was used from common methods in mathematical modeling and computational mathematics. Knowledge discovery through data was the underpinning framework used in this study using a priori mined data. This allowed categorization of activity and articulation of complexity. RESULT: In total, 8966 nursing events were captured over 1639 hours from a total of 22.8 whole time equivalents, and several data sources were mined. The work of specialist nurses in this area is complex in terms of the physical and psychosocial care they provide. The nurses also undertook case management activity such as utilizing a very large network of professionals, and others participated in admission avoidance work and education of patients' families and other staff. CONCLUSION: The work of nurses specializing in hemoglobinopathy care is complex and multidimensional and is likely to contribute to the quality of care in a cost-effective way. An understanding of this complexity can be used as an underpinning to establishing key performance indicators, optimum caseload calculations, and economic evaluation. PMID- 25111408 TI - The relationship between uncontrolled glycemia and the cost of hospitalization. AB - PURPOSE/OBJECTIVE: The purpose of this study was to examine the relationship between hospitalization cost and discharge blood glucose levels among adult diabetes mellitus type 2 patients hospitalized with uncontrolled glycemia without complications. DESIGN: Retrospective cohort analysis examined healthcare billing and laboratory data. SETTING: The study was performed in Chicago, Illinois, in a 269-bed medical center between January 1, 2011, and December 31, 2011. SAMPLE: Patients were placed into 1 of 2 groups at discharge: blood glucose level less than 250 mg/dL or blood glucose level 250 mg/dL or greater. RESULTS: Of the 579 patients with uncontrolled glycemia, 366 met inclusion criteria: diabetes mellitus without complications (International Classification of Diseases, Ninth Revision; 250.0) with abnormal fasting blood glucose (International Classification of Diseases, Ninth Revision; 790.21). Discharge blood glucose levels were 250 mg/dL or greater in 74 patients and less than 250 mg/dL in 292 patients. Mean age of the 2 cohorts was 71.4 (SD, 13.41) years. The majority was male (52.1% and 59.7%, respectively). The median healthcare cost for the entire sample was $3964.34. The mean cost of healthcare for the group with blood glucose of 250 mg/dL or greater at discharge was $4182.65, with a mean length of stay of 8.22 (SD, 3.468) days, while the mean cost of healthcare for the group with blood glucose of less than 250 mg/dL at discharge was $3826.25 and mean length of stay 7.826 (SD, 6.073) days. Analysis of cost was conducted using Pearson chi and was significant for alpha = .05 (P = .037). The odds ratio of having increased healthcare cost with blood glucose of 250 mg/dL or greater was 1.732 with a 95% confidence interval of 0.998 to 3.012. CONCLUSION: The group discharged with blood glucose levels of 250 mg/dL or greater accrued greater cost during hospitalization than did patients who were discharged with blood glucose levels of less than 250 mg/dL. IMPLICATIONS: Today's healthcare system is struggling with cost containment, quality control, and standardization of care. Clinical nurse specialists can evaluate current patient care practices and ensure that the practice setting is fiscally beneficial to future patients and healthcare organizations. PMID- 25111409 TI - Characteristics, resource utilization, and nursing care of patients who undergo percutaneous tracheostomy. AB - PURPOSE/OBJECTIVES: Many critically ill patients require a tracheostomy when unable to be weaned from prolonged ventilator support. This study describes the characteristics, resource use, and outcomes of patients who required a tracheostomy for failure to wean from mechanical ventilation. DESIGN: A retrospective descriptive study was conducted to analyze data from the electronic medical record and hospital databases. SETTING: The setting was a tertiary care hospital with a level I trauma center. SAMPLE: Data from 363 adult subjects who underwent a tracheostomy after prolonged mechanical ventilation during a 1-year period were obtained from hospital databases. All underwent a percutaneous procedure. The majority of subjects were male (62.8%) and white (57.9%), with a median age of 59 years. Nearly half had a trauma diagnosis. RESULTS: Hospital mortality was low (9.9%). Ventilator days, hospital/intensive care unit lengths of stay, and costs were high. Only 7.1% of subjects were discharged directly from the hospital to home. Others were transferred to long-term acute-care hospitals, rehabilitation centers, skilled nursing facilities, and other hospitals. Those who had the tracheostomy done prior to 10 days of ventilation had better outcomes; however, these same subjects had lower acuity scores. Within 1 day of the procedure, ventilator settings were reduced, airway pressures were lower, and level of sedation was improved. CONCLUSIONS: Patients requiring a tracheostomy incur high resource use, and although the majority was transferred to other facilities, the number discharged directly home was low. Improved physiological parameters and reduced ventilator settings following the tracheostomy facilitated weaning from ventilation. IMPLICATIONS: Knowledge of characteristics and outcomes may assist in identifying interventions to reduce the need for tracheostomy or improve outcomes. In particular, the clinical nurse specialist can lead team initiatives to promote weaning prior rather than performing a tracheostomy as well as interventions postprocedure to improve discharge outcomes. PMID- 25111410 TI - Clinical nurse specialist profile. PMID- 25111411 TI - Where the heart is. PMID- 25111412 TI - Impact of the clinical nurse specialist role on the costs and quality of healthcare: policy briefing paper (December, 2013). PMID- 25111413 TI - A new polyoxygenated cyclohexane and other constituents from Kaempferia rotunda and their cytotoxic activity. AB - The isolation of secondary metabolites from a methanolic extract of Kaempferia rotunda yielded 12 compounds (1-12), including a new polyoxygenated cyclohexane compound, (-)-3-acetyl-4-benzoyl-1-benzoyloxymethyl-1,6-diepoxycyclohexan-2,3,4,5 tetrol (1). The structures of the isolated compounds were determined based on their spectroscopic data and comparison with references. All of the isolated compounds were tested for their cytotoxic activity against pancreatic (PSN-1) and breast (MDA-MB231) cancer cell lines. Compound 12 showed moderate cytotoxic activity against PSN-1 and MDA-MB231 without showing any cytotoxicity against the normal cell line, TIG-3. PMID- 25111414 TI - [XVII Portuguese Congress of Rheumatology in a flash]. PMID- 25111415 TI - Infection and rheumatic diseases: cause, consequence or both? PMID- 25111416 TI - Sclerostin and Dkk-1 in patients with ankylosing spondylitis. AB - OBJECTIVE: To determine the serum Dickkopf-related protein 1 (Dkk-1) and sclerostin levels, and their relationship to structural damage and disease activity in patients with ankylosing spondylitis (AS), as well as to compare the serum Dkk-1 and sclerostin levels in patients receiving and not receiving anti TNF-a treatment. MATERIALS AND METHOds: This cross-sectional study included 44 AS patients and 41 healthy age- and gender- -matched controls. Demographic data, disease activity parameters, and Bath Ankylosing Spondylitis Radiologic Index (BASRI) scores were recorded. Serum Dkk-1 and sclerostin levels were measured using commercially available ELISA. RESULTS: Serum Dkk-1 levels were lower (P > 0.05) and sclerostin levels were significantly lower (P < 0.05) in the AS patients than in the controls. Dkk-1 and sclerostin levels were similar in the patients that did and didn't receive anti-TNF-a treatment, and in the patients with active and inactive disease (P > 0.05). There wasn't a correlation between serum Dkk-1 or sclerostin levels, and disease activity indices (P > 0.05). BASRI scores did not correlate with serum Dkk-1 or sclerostin levels (P > 0.05). DISCUSSIOn: Sclerostin expression is impaired in AS, but this is not the case for Dkk-1. The lack of an association between Dkk-1 or sclerostin levels, and anti TNF-a treatment, disease activity indices, and radiological damage might indicate that neither the Dkk-1 nor sclerostin level induce inflammation and radiological damage in AS patients. Pathologic bone formation in AS might be due to molecular dysfunction of sclerostin and Dkk-1 at the cellular level. PMID- 25111417 TI - Osteomyelitis and arthritis of the wrist caused by Mycobacterium intracellulare in an immunocompetent patient: a case report and literature review. AB - Mycobacterium intracellulare causes infection in humans. Involvement of joint and bone, however, is extremely rare. We present the case of an immunocompetent 67 year-old female with chronic swelling of the wrist joint diagnosed as rheumatoid arthritis by her previous physician. Examination revealed an unclosed fistula associated with a puncture, and bone and joint destruction on radiographs. She was diagnosed with osteomyelitis and arthritis due to M. intracellulare on histological and microbiological examinations. She was successfully treated with radical surgical debridement and anti-tuberculous drugs for 1 year and there was no recurrence at 3 years postoperatively. PMID- 25111418 TI - Condyloma acuminatum by human papilloma virus infection in childhood-systemic lupus erythematosus patients. AB - INTRODUCTION: Infections are frequent in childhood-systemic lupus erythematosus (C-SLE) patients, including human papillomavirus (HPV). HPV infection may cause genital and anal warts named condyloma acuminatum (CA). To our knowledge, none case was reported and the prevalence of CA in C-SLE population was not performed. CASE REPORTS: From January 1983 to May 2012, 5,682 patients were followed at the Pediatric Rheumatology Unit from of our University Hospital and 289 (5%) of them met the American College of Rheumatology classification criteria for C- SLE. Four (1.4%) of our female patients had CA. The median age at diagnosis was 13 years. Three of them were sexually active and all of them had active disease and had high risk HPV anogenital warts. Pap smears showed low-grade squamous intraepithelial lesion, guided biopsies identified chronic cervicitis, vulvar, vaginal, anal and/or cervix intraepithelial neoplasia. All of them were under corticosteroids and immunosuppressive drugs. The visible genital warts lesions were eradicated. DISCUSSION: Our patients requires rigorous gynecologic follow-up due to the severe anogenital dysplasia. HPV vaccine should be indicated in all C SLE prior to sexual activity. PMID- 25111419 TI - Reactive arthritis mimicking inflammatory bowel disease arthritis: a challenging diagnosis. AB - Reactive arthritis comprises a subgroup of infection-associated arthritis which occurs after genitourinary or gastrointestinal tract infection in genetically susceptible hosts. Studies have proposed Salmonella, Shigella or Yersinia infection as the microorganisms responsible for the post-dysenteric form. The human leukocyte antigen (HLA)-B27 is a well recognised best-known predisposing factor. We report a case of HLA-B27-associated reactive arthritis after Salmonella goldcoast enteritis, mimicking inflammatory bowel disease arthritis. PMID- 25111420 TI - On the design and analysis of clinical trials with correlated outcomes. AB - The convention in clinical trials is to regard outcomes as independently distributed, possibly conditional on covariates, but in some situations they may be correlated. For example, in infectious diseases, correlation may be induced if participants have contact with a common infectious source, or share hygienic tips that prevent infection. This paper discusses the design and analysis of randomized clinical trials that allow arbitrary correlation among all randomized participants. This perspective generalizes the traditional perspective of strata, where patients are exchangeable within strata, and independent across strata. For theoretical work, we focus on the test of no treatment effect MU(1)-MU(0)=0 when the n dimensional vector of outcomes follows a Gaussian distribution with known n * n covariance matrix Sigma, where the half randomized to treatment (placebo) have mean response MU(1)(MU(0)). We show how the new test corresponds to familiar tests in simple situations for independent, exchangeable, paired, and clustered data. We also discuss the design of trials where Sigma is known before or during randomization of patients and evaluate randomization schemes based on such knowledge. We provide two complex examples to illustrate the method, one for a study of 23 family clusters with cardiomyopathy, and the other where the malaria attack rates vary within households and clusters of households in a Malian village. PMID- 25111421 TI - Correlation between inflammatory markers and insulin resistance in pregnancy. AB - Gestational diabetes mellitus (GDM) is associated with an increased risk of postpartum type 2 diabetes mellitus and cardiovascular risk factors, such as obesity, hypertension, dyslipidaemia and systemic inflammation. We aimed to evaluate further lipid profile and inflammatory status assessed by high sensitive C-reactive protein (hsCRP) and TNF-alpha in GDM. Based on oral glucose tolerance testing, participants were stratified into three groups: normal 50 g glucose challenge test (GCT), normal 100 g glucose tolerance test (NOGTT) (control group) (n = 40); abnormal GCT NOGTT (glucose intolerance) (n = 37); and GDM (n = 39), defined by Carpenter and Coustan. The three groups did not demonstrate significantly different hsCRP levels (p = 0.4180) and lipid profile parameters, such as total cholesterol (p = 0.4210) and LDL-cholesterol (p = 0.4440) levels. Triglycerides (p = 0.0150) and atherogenic index of the plasma levels (p = 0.0280) were slightly higher in the GDM group. But, TNF-alpha levels increased significantly in the GDM (p < 0.0001) and in glucose intolerance (p = 0.0062) groups as compared with the control group. Among the metabolic syndrome components, insulin resistance was apparently associated with TNF-alpha, whereas dyslipidaemia was slightly associated with hsCRP because of the effects of maternal age on lipid markers. These findings suggest that TNF-alpha has a stronger correlation with pregnancy-associated insulin resistance than hsCRP at 24 to 28 weeks' gestation. PMID- 25111422 TI - My friend and mentor: Robert A. Jahrsdoerfer, M.D. PMID- 25111423 TI - Tympanic membrane manipulation to treat symptoms of patulous eustachian tube. AB - OBJECTIVE: Patulous eustachian tube (PET) can have a significant negative impact on a patient's quality of life. Previous work has demonstrated that temporarily mass loading and stiffening the tympanic membrane significantly reduces these symptoms. This study examined KTP laser myringoplasty (LM) and cartilage tympanoplasty (CT) as a means to manipulate the tympanic membrane to alleviate PET symptoms. STUDY DESIGN: Retrospective case review. SETTING: Academic tertiary care referral hospital. PATIENTS: Patients (n = 20) were identified from the senior authors' (M.B.) specialty eustachian tube disorders clinic. Patients met previously established diagnostic criteria for PET. All patients had a clinically apparent flaccid segment of the eardrum and had symptom improvement after simple mass loading of their eardrum in the clinic. INTERVENTIONS: Patients in this study received either KTP LM (10 patients, 15 ears) or CT (10 patients, 11 ears) to treat their flaccid eardrum segment in an attempt to alleviate PET symptoms. MAIN OUTCOME MEASURES: Preoperative and postoperative questionnaire scores and tympanometry measurements were compared. RESULTS: Patients undergoing CT for PET had a significant reduction in their symptoms of autophony (p <= 0.001), conducted breath sounds (p = 0.001), and aural fullness (p = 0.009). KTP LM did not significantly reduce symptoms. CONCLUSION: Cartilage tympanoplasty provides a safe and accessible surgical option for the treatment of PET and significantly reduces the symptoms of autophony, conducted breath sounds, and aural fullness. Further studies are needed to investigate whether addressing PET symptoms simultaneously from both the tympanic membrane and the eustachian tube orifice can improve patient symptoms even further. PMID- 25111425 TI - Plasmon resonance-enhanced circularly polarized luminescence of self-assembled meso-tetrakis(4-sulfonatophenyl)porphyrin-surfactant complexes in interaction with Ag nanoparticles. AB - The chiroptical properties of an anionic meso-tetrakis(4 sulfonatophenyl)porphyrin (TPPS) complexed with cationic surfactants were enhanced by interaction with silver nanoparticles (AgNPs) in acidic solution. Improvement in chiroptical properties was revealed by circular dichroism (CD) and circularly polarized luminescence (CPL), with |gabs| and |glum| values reaching 0.05 and 0.001 at 303 K, respectively. PMID- 25111424 TI - Scleral cross-linking using riboflavin and ultraviolet-a radiation for prevention of progressive myopia in a rabbit model. AB - Our study demonstrates the effect of scleral cross-linking using riboflavin and ultraviolet-A radiation on the development of axial myopia in a rabbit model. Axial length of the eyeball was measured by A-scan ultrasound in 22 New Zealand white rabbits aged 13 days. The right eyes then underwent 360-degree conjunctival peritomy with (experimental group, n = 11) or without (control group, n = 11) scleral cross-linking, followed by tarsorrhaphy. The left eyes served as a control eye. In the experimental group, the right eyeballs were divided into quadrants, and every quadrant had either 2 (n = 8) or 6 (n = 3) scleral irradiation zones, each with an area of 0.2 cm2 and radius of 4 mm. Cross-linking was performed by dropping 0.1% dextran-free riboflavin-5-phosphate onto the irradiation zones at 20 s before ultraviolet-A irradiation and every 20 s during the 200-s irradiation time. UVA radiation (370 nm) was applied perpendicular to the sclera at 57 mW/cm2 (total UVA light dose, 57 J/cm2). Tarsorrhaphies were removed on day 55, followed by repeated axial-length measurement. In the control group, mean axial length in the right eyes increased from 10.50 +/- 0.67 mm at baseline to 15.69 +/- 0.39 mm 55 days later, for a mean change of 5.19 +/- 0.85 mm. In the experimental group, corresponding values were 10.68 +/- 0.74 mm and 14.29 +/- 0.3 mm, for a mean change of 3.61 +/- 0.76 mm. The between-group difference in the change in mean axial length was statistically significant (p < 0.001, Mann-Whitney nonparametric test). The present manuscript demonstrates that scleral cross-linking with riboflavin and ultraviolet-A radiation effectively prevents occlusion-induced axial elongation in a rabbit model. PMID- 25111426 TI - Somatic aberrations of mismatch repair genes as a cause of microsatellite unstable cancers. AB - Lynch syndrome (LS) is caused by germline mutations in mismatch repair (MMR) genes, resulting in microsatellite-unstable tumours. Approximately 35% of suspected LS (sLS) patients test negative for germline MMR gene mutations, hampering conclusive LS diagnosis. The aim of this study was to investigate somatic MMR gene aberrations in microsatellite-unstable colorectal and endometrial cancers of sLS patients negative for germline MMR gene mutations. Suspected LS cases were selected from a retrospective Clinical Genetics Department diagnostic cohort and from a prospective multicentre population-based study on LS in The Netherlands. In total, microsatellite-unstable tumours of 40 sLS patients (male/female 20/20, median age 57 years) were screened for somatic MMR gene mutations by next-generation sequencing. In addition, loss of heterozygosity (LOH) of the affected MMR genes in these tumours as well as in 68 LS-associated tumours and 27 microsatellite-unstable tumours with MLH1 promoter hypermethylation was studied. Of the sLS cases, 5/40 (13%) tumours had two pathogenic somatic mutations and 16/40 (40%) tumours had a (likely) pathogenic mutation and LOH. Overall, LOH of the affected MMR gene locus was observed in 24/39 (62%) tumours with informative LOH markers. Of the LS cases and the tumours with MLH1 promoter hypermethylation, 39/61 (64%) and 2/21 (10%) tumours, respectively, demonstrated LOH. Half of microsatellite-unstable tumours of sLS patients without germline MMR gene mutations had two (likely) deleterious somatic MMR gene aberrations, indicating their sporadic origin. Therefore, we advocate adding somatic mutation and LOH analysis of the MMR genes to the molecular diagnostic workflow of LS. PMID- 25111427 TI - Effect of small molecule vasopressin V1a and V2 receptor antagonists on brain edema formation and secondary brain damage following traumatic brain injury in mice. AB - The attenuation of brain edema is a major therapeutic target after traumatic brain injury (TBI). Vasopressin (AVP) is well known to play a major role in the regulation of brain water content and vasoendothelial functions and to be involved in brain edema formation. Therefore, the aim of the current study was to analyze the antiedematous efficacy of a clinically relevant, nonpeptidic AVP V1a and V2 receptor antagonists. C57Bl6 mice were subjected to controlled cortical impact (CCI) and V1a or V2 receptors were inhibited by using the highly selective antagonists SR-49059 or SR-121463A either by systemic (intraperitoneal, IP) or intracerebroventricular (ICV) application. After 24 h, brain edema, intracranial pressure (ICP), and contusion volume were assessed. Systemically applied AVP receptor antagonists could not reduce secondary lesion growth. In contrast, ICV administration of AVP V1a receptor antagonist decreased brain edema formation by 68%, diminished post-traumatic increase of ICP by 46%, and reduced secondary contusion expansion by 43% 24 h after CCI. The ICV inhibition of V2 receptors resulted in significant reduction of post-traumatic brain edema by 41% 24 h after CCI, but failed to show further influence on ICP and lesion growth. Hence, centrally applied vasopressin V1a receptor antagonists may be used to reduce brain edema formation after TBI. PMID- 25111429 TI - In-session processes of brief motivational interventions in two trials with mandated college students. AB - OBJECTIVE: Each year, thousands of college students receive mandated intervention as a sanction for alcohol use or alcohol-related behavior. For these mandated students, brief motivational interventions (BMIs) are currently the most efficacious individual intervention. However, little is known about how the technical (therapist behaviors) and relational (e.g., global ratings of therapist empathy) components of BMIs influence client language as well as subsequent change in alcohol use and consequences. METHOD: This study used the Motivational Interviewing Skills Code (MISC 2.0; Miller, Moyers, Ernst, & Amrhein, 2003) to code BMI sessions from 2 randomized clinical trials that facilitated significant reductions in alcohol use (Study 1, n = 91) and alcohol-related consequences (Study 2, n = 158) in mandated students. RESULTS: There were significant relationships among therapist behaviors, global scores, and client language both for and against change, yet there were no links between in-session client language and subsequent changes in alcohol use or problems. In contrast, relational aspects of motivational interviewing (MI; global ratings of therapist MI Spirit and client self-exploration) were most predictive of postsession alcohol use. Mediation models incorporating both technical and relational components revealed that higher levels of client self-exploration mediated the relationship between higher therapist ratings of MI Spirit and reduced drinking at follow-up. CONCLUSIONS: Findings highlight the importance of considering how both technical and relational components of MI may influence alcohol use in mandated college students and also suggest more exact analyses to better understand this complex relationship. PMID- 25111431 TI - Testosterone treatment and MMPI-2 improvement in transgender men: a prospective controlled study. AB - OBJECTIVE: Most transgender men desire to receive testosterone treatment in order to masculinize their bodies. In this study, we aimed to investigate the short term effects of testosterone treatment on psychological functioning in transgender men. This is the 1st controlled prospective follow-up study to examine such effects. METHOD: We examined a sample of transgender men (n = 48) and nontransgender male (n = 53) and female (n = 62) matched controls (mean age = 26.6 years; 74% White). We asked participants to complete the Minnesota Multiphasic Personality Inventory (2nd ed., or MMPI-2; Butcher, Graham, Tellegen, Dahlstrom, & Kaemmer, 2001) to assess psychological functioning at baseline and at the acute posttreatment follow-up (3 months after testosterone initiation). Regression models tested (a) Gender * Time interaction effects comparing divergent mean response profiles across measurements by gender identity; (b) changes in psychological functioning scores for acute postintervention measurements, adjusting for baseline measures, comparing transgender men with their matched nontransgender male and female controls and adjusting for baseline scores; and (c) changes in meeting clinical psychopathological thresholds. RESULTS: Statistically significant changes in MMPI-2 scale scores were found at 3 month follow-up after initiating testosterone treatment relative to baseline for transgender men compared with female controls (female template): reductions in Hypochondria (p < .05), Depression (p < .05), Hysteria (p < .05), and Paranoia (p < .01); and increases in Masculinity-Femininity scores (p < .01). Gender * Time interaction effects were found for Hysteria (p < .05) and Paranoia (p < .01) relative to female controls (female template) and for Hypochondria (p < .05), Depression (p < .01), Hysteria (p < .01), Psychopathic Deviate (p < .05), Paranoia (p < .01), Psychasthenia (p < .01), and Schizophrenia (p < .01) compared with male controls (male template). In addition, the proportion of transgender men presenting with co-occurring psychopathology significantly decreased from baseline compared with 3-month follow-up relative to controls (p < .05). CONCLUSIONS: Findings suggest that testosterone treatment resulted in increased levels of psychological functioning on multiple domains in transgender men relative to nontransgender controls. These findings differed in comparisons of transgender men with female controls using the female template and with male controls using the male template. No iatrogenic effects of testosterone were found. These findings suggest a direct positive effect of 3 months of testosterone treatment on psychological functioning in transgender men. PMID- 25111430 TI - Individual versus significant-other-enhanced brief motivational intervention for alcohol in emergency care. AB - OBJECTIVE: Effects of brief motivational interventions (BMIs) for heavy drinkers identified by alcohol-related emergency department (ED) visits are mixed. The successes of including significant others (SOs) in behavioral treatment suggest that involving SOs in ED-delivered BMI might prove beneficial. This study investigated the relative efficacy of an SO-enhanced motivational intervention (SOMI) compared with an individual motivational intervention (IMI) to address heavy drinking in emergency care settings. METHOD: ED (n = 317) or trauma unit (n = 89) patients were randomly assigned to receive either an IMI or an SOMI and were reassessed at 6 and 12 months for alcohol consumption, alcohol-related consequences, and perceived alcohol-specific SO support. RESULTS: Generalized estimating equation analyses showed consistent reductions over time for both alcohol consumption and consequences. At 1-year follow-up, the average reduction in total drinks consumed per week was greater for patients in the SOMI condition than the IMI condition. In SOMI, 9.4% more patients moved to within the national guidelines for weekly drinking than did IMI patients. Frequency of heavy drinking and negative alcohol consequences showed no differential effects of intervention. CONCLUSIONS: Emergence of a modest treatment effect at 12 months suggests that SO involvement in the SOMI condition may have led to more sustained positive influence on patient drinking than in the IMI condition. Implications and limitations regarding SO involvement in brief treatment are discussed. PMID- 25111433 TI - Behavior therapy for depressed breast cancer patients: predictors of treatment outcome. AB - OBJECTIVE: Major depressive disorder (MDD) is the most common psychiatric disorder among breast cancer patients and is associated with substantial functional impairment. Although several outcome studies have explored the utility of psychotherapy for breast cancer patients with subsyndromal depression symptoms, only a few clinical trials have explored the efficacy of behavior therapy for patients with well-diagnosed MDD. An additional limitation of this research is that little is known about factors that best predict treatment outcome. METHOD: In the context of a recent randomized trial of behavior activation and problem-solving therapy for depressed breast cancer patients (n = 80; Hopko et al., 2011), this study explored predictors of treatment outcome with selected demographic (age, education, marital status, occupational status), psychosocial (pretreatment depression and environmental reward, coexistent anxiety disorders, social support, history of psychotherapy) and cancer-related variables (cancer stage, duration of cancer diagnosis, and cancer treatment). RESULTS: Positive treatment outcome as defined by Beck Depression Inventory-II (Beck et al., 1996) response and remission criteria was associated with being married, increased social support, not actively undergoing cancer treatment during psychotherapy, and having a history of psychotherapy. CONCLUSIONS: The efficacy of behavior therapy for depressed breast cancer patients may depend on several patient variables. Implications for the provision of behavior therapy for breast cancer patients are discussed. PMID- 25111432 TI - Social network influences on initiation and maintenance of reduced drinking among college students. AB - OBJECTIVE: To determine whether (a) social networks influence the extent to which college students initiate and/or maintain reductions in drinking following an alcohol intervention and (b) students with riskier networks respond better to a counselor-delivered, vs. a computer-delivered, intervention. METHOD: Mandated students (N = 316; 63% male) provided their perceptions of peer network members' drinking statuses (e.g., heavy drinker) and how accepting each friend would be if the participant reduced his or her drinking. Next, they were randomized to receive a brief motivational intervention (BMI) or Alcohol Edu for Sanctions (EDU). In latent growth models controlling for baseline levels on outcomes, influences of social networks on 2 phases of intervention response were examined: initiation of reductions in drinks per heaviest week, peak blood alcohol content (BAC), and consequences at 1 month (model intercepts) and maintenance of reductions between 1 and 12 months (model slopes). RESULTS: Peer drinking status predicted initiation of reductions in drinks per heaviest week and peak BAC; peer acceptability predicted initial reductions in consequences. Peer Acceptability * Condition interactions were significant or marginal for all outcomes in the maintenance phase. In networks with higher perceived acceptability of decreasing use, BMI and EDU exhibited similar growth rates. In less accepting networks, growth rates were significantly steeper among EDU than BMI participants. For consumption outcomes, lower perceived peer acceptability predicted steeper rates of growth in drinking among EDU but not BMI participants. CONCLUSIONS: Understanding how social networks influence behavior change and how interventions mitigate their influence is important for optimizing efficacy of alcohol interventions. PMID- 25111434 TI - Bis-quaternary gemini surfactants as components of nonviral gene delivery systems: a comprehensive study from physicochemical properties to membrane interactions. AB - Gemini surfactants have been successfully used as components of gene delivery systems. In the present work, a family of gemini surfactants, represented by the general structure [CmH2m+1(CH3)2N(+)(CH2)sN(+)(CH3)2CmH2m+1]2Br(-), or simply m-s m, was used to prepare cationic gene carriers, aiming at their application in transfection studies. An extensive characterization of the gemini surfactant based complexes, produced with and without the helper lipids cholesterol and DOPE, was carried out in order to correlate their physico-chemical properties with transfection efficiency. The most efficient complexes were those containing helper lipids, which, combining amphiphiles with propensity to form structures with different intrinsic curvatures, displayed a morphologically labile architecture, putatively implicated in the efficient DNA release upon complex interaction with membranes. While complexes lacking helper lipids were translocated directly across the lipid bilayer, complexes containing helper lipids were taken up by cells also by macropinocytosis. This study contributes to shed light on the relationship between important physico-chemical properties of surfactant-based DNA vectors and their efficiency to promote gene transfer, which may represent a step forward to the rational design of gene delivery systems. PMID- 25111435 TI - Acquired hemophilia: a potentially life-threatening etiology of persistent bleeding after Mohs micrographic surgery. PMID- 25111436 TI - Platelet-rich plasma for androgenetic alopecia: a pilot study. AB - BACKGROUND: Androgenetic alopecia is a common condition, with severe attendant psychosocial implications, and for which it is difficult to obtain a satisfactory degree of clinical improvement. OBJECTIVE: To explore the possible clinical benefit of injecting platelet-derived growth factors into the scalp of patients using a specific autologous blood concentrate. MATERIALS AND METHODS: Two injections of a leukocyte platelet-rich plasma (L-PRP) with the addition of concentrated plasmatic proteins were administered at baseline and after 3 months (single spin at baseline and double-spin centrifugation at 3 months). Macrophotographs were taken at baseline and after 6 months, and 2 independent evaluators rated them using Jaeschke rating of clinical change. RESULTS: Sixty four consecutive patients were enrolled. Some improvement was seen in all patients by 1 evaluator and in 62 by the other. The mean change in clinical rating was 3.2 (95% confidence interval [CI], 2.9-3.5) and 3.9 (95% CI, 3.5-4.3), and the proportion of patients reaching a clinically important difference was 40.6% and 54.7%, according to the 2 evaluators, respectively. CONCLUSION: Our pilot study may provide preliminary evidence that this treatment may induce some degree of clinical advantage for male- and female-pattern baldness. This may warrant the design of randomized controlled clinical trials to formally test this procedure. PMID- 25111437 TI - Fat reduction in the inner thigh using a prototype cryolipolysis applicator. AB - BACKGROUND: Previous clinical studies have investigated cryolipolysis for noninvasive reduction of fat in abdomens, outer thighs, flanks, and backs. This study investigated feasibility of cryolipolysis for inner thigh treatment. OBJECTIVE: This pilot study evaluated a cryolipolysis flat cup vacuum applicator for treatment of inner thigh fat. METHODS: A prototype vacuum applicator was used to treat n = 11 subjects in a single-side inner thigh study. Cryolipolysis treatment was delivered to the larger thigh while the contralateral thigh served as a control. Follow-ups were conducted at 8 and 16 weeks. Equalization treatments were subsequently delivered to the contralateral thigh. Safety was assessed by monitoring side effects and adverse events. Efficacy was evaluated by ultrasound imaging, clinical photography, and patient surveys. RESULTS: Side effects were typical and resolved spontaneously. Efficacy was demonstrated with ultrasound measurements showing 83% of subjects attained some level of fat layer reduction. Normalized mean reduction in fat layer thickness was 20%, corresponding to 3.3 mm. Patient surveys revealed 91% were satisfied and 82% felt inner thigh cryolipolysis was comfortable. Clinical photographs revealed visible reduction in inner thigh contour after treatment. CONCLUSION: This study demonstrates feasibility of safe and efficacious cryolipolysis treatment to the inner thigh. PMID- 25111438 TI - A comparison of the scar prevention effect between carbon dioxide fractional laser and pulsed dye laser in surgical scars. AB - BACKGROUND: The use of ablative lasers based on the fractional approach is a novel strategy for the treatment of postoperative and acne scars in addition to wrinkles. OBJECTIVE: To evaluate and compare the efficacy of carbon dioxide ablative fractional laser (AFL) and the pulsed dye laser (PDL) for the improvement of surgical scars. MATERIALS AND METHODS: Fourteen Korean patients with surgical scars were enrolled for this study. Half of each scar was treated with a 10,600-nm AFL and the contralateral half with the 595-nm PDL. For early intervention of the postoperative scar, the laser treatments were begun after 2 weeks from the Mohs micrographic surgery. RESULTS: Both PDL and AFL produced statistically significant improvements. However, comparatively, there was no statistical difference between them. In each variable, AFL was more effective than PDL in the improvement of pliability and thickness. In contrast, PDL was superior to AFL in the improvement of vascularity and pigmentation. CONCLUSION: Pulsed dye laser and AFL treatments for surgical scar provide significant improvement. Pulsed dye laser was more effective in color of scar compared with AFL, which showed marked improvement in the contour of scar. Overall improvement was not statistically different in the Vancouver Scar Scale. PMID- 25111440 TI - Sulfur copolymer nanowires with enhanced visible-light photoresponse. AB - Sulfur copolymer nanowires have been reported for the first time as highly stable visible-light-active photocatalysts for photoelectrochemical water splitting depending on their size and sulfur content. The as-prepared sulfur copolymer nanowires can serve as a sulfur source and templates to create metal sulfide/copolymer heterocatalysts. PMID- 25111441 TI - One-pot method for synthesizing spherical-like metal sulfide-reduced graphene oxide composite powders with superior electrochemical properties for lithium-ion batteries. AB - A facile, one-pot method for synthesizing spherical-like metal sulfide-reduced graphene oxide (RGO) composite powders by spray pyrolysis is reported. The direct sulfidation of ZnO nanocrystals decorated on spherical-like RGO powders resulted in ZnS-RGO composite powders. ZnS nanocrystals with a size below 20 nm were uniformly dispersed on spherical-like RGO balls. The discharge capacities of the ZnS-RGO, ZnO-RGO, bare ZnS, and bare ZnO powders at a current density of 1000 mA g(-1) after 300 cycles were 628, 476, 230, and 168 mA h g(-1), respectively, and the corresponding capacity retentions measured after the first cycles were 93, 70, 40, and 21 %, respectively. The discharge capacity of the ZnS-RGO composite powders at a high current density of 4000 mA g(-1) after 700 cycles was 437 mA h g(-1). The structural stability of the highly conductive ZnS-RGO composite powders with ultrafine crystals during cycling resulted in excellent electrochemical properties. PMID- 25111439 TI - Pyrano-isochromanones as IL-6 inhibitors: synthesis, in vitro and in vivo antiarthritic activity. AB - Bergenin (1), a unique fused C-glycoside isolated from Bergenia species, possesses interesting anti-inflammatory and antipain activities. To study SAR of this scaffold, first-generation derivatives were synthesized and evaluated for inhibition of lymphocyte proliferation and production of pro-inflammatory cytokines. The C-7 substituted derivatives showed inhibition of IL-6 as well as TNF-alpha production. Bergenin and its most potent IL-6 inhibitor derivatives 4e and 4f were then investigated in a panel of in vitro and in vivo inflammation/arthritis models. These compounds significantly decreased the expression of NF-kB and IKK-beta in THP-1 cells. In in vivo study in BALB/c mice, a dose-dependent inhibition of SRBC-induced cytokines, reduction in humoral/cell mediated immunity, and antibody titer was observed. The CIA study in DBA/1J mice indicated that compounds led to reduction in swelling of paws, cytokine levels, and anticollagen IgG1/IgG2a levels. The significant in vivo immunosuppressive efficacy of pyrano-isochromanones demonstrates the promise of this scaffold for development of next-generation antiarthritic drugs. PMID- 25111443 TI - Iridium-catalyzed enantioselective allyl-allylsilane cross-coupling. AB - An enantioselective allyl-allylsilane cross-coupling involving racemic branched allylic alcohols and allylsilanes is reported. An iridium-(P,olefin) phosphoramidite complex enables the transformation with high regio- and stereoselectivity under operationally simple conditions. The utility of the coupling is demonstrated in a concise catalytic, enantioselective synthesis of a pyrethroid insecticide protrifenbute. PMID- 25111442 TI - An automated three-dimensional detection and segmentation method for touching cells by integrating concave points clustering and random walker algorithm. AB - Characterizing cytoarchitecture is crucial for understanding brain functions and neural diseases. In neuroanatomy, it is an important task to accurately extract cell populations' centroids and contours. Recent advances have permitted imaging at single cell resolution for an entire mouse brain using the Nissl staining method. However, it is difficult to precisely segment numerous cells, especially those cells touching each other. As presented herein, we have developed an automated three-dimensional detection and segmentation method applied to the Nissl staining data, with the following two key steps: 1) concave points clustering to determine the seed points of touching cells; and 2) random walker segmentation to obtain cell contours. Also, we have evaluated the performance of our proposed method with several mouse brain datasets, which were captured with the micro-optical sectioning tomography imaging system, and the datasets include closely touching cells. Comparing with traditional detection and segmentation methods, our approach shows promising detection accuracy and high robustness. PMID- 25111446 TI - Electroconvulsive therapy in obsessive-compulsive disorder: a chart review and evaluation of its potential therapeutic effects. AB - In a chart review of patients with obsessive-compulsive disorder (OCD) attending a university clinic, ECT was prescribed for five subjects (1.2%), only because of severe intervening manic (N=1) or depressive episodes (N=4). Although affective symptoms improved in four of the five patients, OCD symptoms remained unchanged (N=3) or transiently worsened (N=2). PMID- 25111444 TI - Evaluation of staging and early response to chemotherapy with whole-body diffusion-weighted MRI in malignant lymphoma patients: A comparison with FDG PET/CT. AB - BACKGROUND: To examine the utility of diffusion-weighted MRI (DW-MRI) for staging and early response to chemotherapy assessment in lymphoma patients as compared with fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). METHODS: Twenty-eight patients with histologically confirmed malignant lymphoma underwent both MRI and FDG-PET/CT before (pretreatment) and after two courses of chemotherapy (mid-treatment). Staging with MRI (DW-MRI alone and with T2-weighted images) and FDG-PET was compared visually, and the concordance rate (kappa value, kappa) was calculated. To evaluate early response to chemotherapy, patients were divided into two groups, lesion-positive (LP) and lesion-negative (LN), based on a proposed original criterion. Progression-free survival (PFS) was compared between the groups using the Kaplan-Meier method. RESULTS: The stage diagnosed with DW-MRI alone and with FDG-PET/CT was concordant in 22 patients (kappa = 0.71; P < 0.05), and by adding T2-weighted images, the number of concordant patients increased to 26 (kappa = 0.90; P < 0.05). On mid-treatment imaging, 19 patients were diagnosed as LN from both modalities. PFS differed significantly between LP and LN on both DW-MRI (P = 0.0013) and FDG-PET/CT (P = 0.037). CONCLUSION: DW-MRI is a promising tool for staging and evaluation of early response to chemotherapy in patients with lymphoma. PMID- 25111445 TI - Mechanical characterization of a bifunctional Tetronic hydrogel adhesive for soft tissues. AB - Although a number of tissue adhesives and sealants for surgical use are currently available, attaining a useful balance in high strength, high compliance, and low swelling has proven difficult. Recent studies have demonstrated that a four-arm poly(propylene oxide)-poly(ethylene oxide) block copolymer, Tetronic, can be chemically modified to form a hydrogel tissue adhesive (Cho et al., Acta Biomater 2012;8:2223-2232; Barrett et al., Adv Health Mater 2012;1-11; Balakrishnan, Evaluating mechanical performance of hydrogel-based adhesives for soft tissue applications. Clemson University, All Theses, Paper 1574: Tiger Prints; 2013). Building on the success of these studies, this study explored bifunctionalization of Tetronic with acrylates for chemical crosslinking of the hydrogel and N hydroxysuccinimide (NHS) for reaction with tissue amines. The adhesive bond strengths of various uni and bifunctional Tetronic blends (T1107 ACR: T1107 ACR/NHS) determined by lap shear testing ranged between 8 and 74 kPa, with the 75:25 (T1107 ACR: T1107 ACR/NHS) blend displaying the highest value. These results indicated that addition of NHS led to improvement of tissue bond strength over acrylation alone. Furthermore, ex vivo pressure tests using the rat bladder demonstrated that the bifunctional Tetronic adhesive exhibited high compliance and maintained pressures under hundreds of filling and emptying cycles. Together, the results of this study provided evidence that the bifunctional Tetronic adhesive with a proper blend ratio may be used to achieve an accurate balance in bulk and tissue bond strengths, as well as the compliance and durability for soft tissue such as the bladder. PMID- 25111447 TI - [Validation of the German short version of the Murray Secretion Rating Scale]. AB - OBJECTIVE: Accumulation of secretions in hypopharynx, aditus vestibule, and trachea is often found in cases of severe dysphagia and is considered a cardinal trait of high clinical and therapeutic importance. For the graduation of the severity level of accumulated secretions, a short version of the 4-point Murray secretion scale is available, which is also integrated into the protocol of the fiberoptic endoscopic evaluation of swallowing (FEES) according to the Langmore standard. This study aimed at the validation of the German translation of this short version in order to facilitate a uniform, standardized evaluation of the accumulation of secretions in dysphagic patients in the German language area. MATERIAL AND METHODS: For the examination of reliability and validity, a reference standard was defined by 2 dysphagia experts on the basis of 40 video files of the FEES examination, 10 videos for each of the severity grades. Afterwards, these videos were rated independently by 4 raters and re-rated in a new randomized order 2 weeks later. RESULTS: Both the intra-rater reliability (tau>0,830***) and the inter-rater reliability (Kendalls W>0,890***) were highly significant and can be considered good. The same is valid for the correlation of ratings with the reference standard (tau=0,969***). CONCLUSIONS: The German translation of the short version of the 4-point Murray secretion scale is recommendable as a reliable and valid instrument for the graduation of the cardinal trait of oropharyngeal dysphagia and also as an evidence-based instrument for standardized use in the German language area. PMID- 25111448 TI - [Inpatient vs. outpatient costs analysis of septumplasty in Germany]. AB - The septumplasty is realized inpatient and outpatient in different countries. Caused by the pressure of reduction of expenses there is the question of the economic benefit if done outpatient in Germany. A comparison of the inpatient and outpatient gratification will be done. There is a yearly potential of cost reduction of 180 million euro, if the operation would be done as an outpatient procedure. From the hospital view actual there is no economical recommendation doing an outpatient septumplasty caused by the poor outpatient remuneration. That's why an adjustment of the outpatient remuneration should be done. Actual there is no medical or economical recommendation doing the septumplasty as an outpatient procedere. PMID- 25111450 TI - Catalytic purification of directly written nanostructured Pt microelectrodes. AB - In the majority of cases, nanostructures prepared by focused electron beam induced deposition employing an organometallic precursor contain predominantly carbon-based ligand dissociation products. This is unfortunate with regard to using this high-resolution direct-write approach for the preparation of nanostructures for various fields, such as mesoscopic physics, micromagnetism, metaoptical phenomena in the visible spectral range, or others. Following early attempts of postprocessing Pt-based structures prepared by focused electron beam induced deposition at several hundred degrees Celsius in a reactive gas atmosphere, recent work has focused on developing in situ purification processes by using a stationary O2 flux in combination with electron irradiation to oxidize the carbonaceous component of the deposits. Here we show that this purification process is driven by the catalytic activity of Pt and in fact does not rely on the parallel electron irradiation process to function, if the O2 exposure is done in a pulsed fashion. We suggest a multistep cleaning mechanism which results in pure, nanoporous Pt. By suitably chosen beam parameters, high-resolution Pt dot and line structures with dimensions below 10 nm can thus be conveniently obtained. In temperature-dependent resistance measurements, we find the typical metallic behavior of Pt. In low-temperature magnetoresistance measurements, we see clear evidence for weak antilocalization effects and deduce a dephasing length of 234 nm at 1.2 K. We consider this to be a promising starting point for developing this approach into a versatile preparation technique for Pt-based mesoscopic structures, in particular since the purification process can be run in parallel on different deposits. We furthermore anticipate that our results will spur further research on purification approaches for nanostructures prepared by focused electron beam induced deposition containing a catalytically active metal species such as Pd-, Fe-, or Co-based deposits. PMID- 25111449 TI - The relative validity and repeatability of an FFQ for estimating intake of zinc and its absorption modifiers in young and older Saudi adults. AB - OBJECTIVE: To assess the relative validity and repeatability of a sixty-four-item FFQ for estimating dietary intake of Zn and its absorption modifiers in Saudi adults. In addition, we used the FFQ to investigate the effect of age and gender on these intakes. DESIGN: To assess validity, all participants completed the FFQ (FFQ1) and a 3 d food record. After 1 month, the FFQ was administered for a second time (FFQ2) to assess repeatability. SETTING: Jeddah, Saudi Arabia. SUBJECTS: One hundred males and females aged 20-30 years and 60-70 years participated. RESULTS: Mean intakes of Zn and protein from FFQ1 were significantly higher than those from the food record while there were no detectable differences between tools for measurement of phytic acid intake. Estimated intakes of Zn, protein and phytate by both approaches were strongly correlated (P<0.001). Bland-Altman analysis showed for protein that the difference in intake as measured by the two methods was similar across the range of intakes while for Zn and phytic acid, the difference increased with increasing mean intake. Zn and protein intakes from FFQ1 and FFQ2 were highly correlated (r>0.68, P<0.001) but were significantly lower at the second measurement (FFQ2). Older adults consumed less Zn and protein compared with young adults. Intakes of all dietary components were lower in females than in males. CONCLUSIONS: The FFQ developed and tested in the current study demonstrated reasonable relative validity and high repeatability and was capable of detecting differences in intakes between age and gender groups. PMID- 25111455 TI - Impact of sympathetic dysfunction in the etiology of overactive bladder in women: A preliminary study. AB - AIMS: We investigated the effects of autonomic sympathetic dysfunction in the etiology of overactive bladder (OAB) in women, by assessing the sympathetic skin response (SSR). METHODS: In total, 40 women with OAB and 15 volunteers were enrolled. Group 1 (n = 20) consisted of patients who benefitted from oral anticholinergics, Group 2 (n = 20) consisted of patients who were refractory to oral anticholinergics, and the volunteers (n = 15) were the control group. All patients were asked to complete OAB-SF questionnaires. The absence of SSR was accepted as significant. Detailed physical examinations including neurological examinations were performed. All patients underwent SSR tests on the skin of the hands, feet, and genital area in our neurology department using electromyography, and SSR responses were recorded. Statistical significance was accepted at P < 0.05. RESULTS: The mean age was 47.2 +/- 12.4 years. In total, 55 women were evaluated (20 in Group 1, 20 in Group 2, and 15 in the control group). Mean OAB scores were similar between groups 1 and 2, although urgency was significantly higher in Group 2 than 1. The absence of SSR was significantly higher in Group 2 than 1 (P = 0.01). Impaired SSR was observed more commonly in Group 2 than 1. All controls had normal SSRs. CONCLUSIONS: Regional dysfunction in the autonomic nervous system may be part of OAB's etiology. SSR may be a candidate test for determining early OAB, and may also be useful for predicting antimuscarinic refractory patients. PMID- 25111456 TI - Power spectral changes of the superimposed M wave during isometric voluntary contractions of increasing strength. AB - INTRODUCTION: We examined the power spectral changes of the compound muscle action potential (M wave) evoked during isometric contractions of increasing strength. METHODS: Surface electromyography (sEMG) of the vastus lateralis and medialis was recorded from 20 volunteers who performed 4-s step-wise isometric contractions of different intensities. A maximal M wave was elicited by a single stimulus to the femoral nerve and superimposed on the voluntary contractions. The spectral characteristics (Fmean and Fmedian) of sEMG and M-wave signals were calculated. RESULTS: M-wave spectral indicators increased systematically with contraction intensity up to 60% MVC and then leveled off at higher forces. Over the 10-60% MVC range, the increase in spectral indicators was 3 times higher for M waves (36%) than for sEMG (12%). CONCLUSIONS: The consistent increase in M-wave spectral characteristics with force is due to the fact that the number of motor units recruited by the superimposed supramaximal stimulus is approximately stable. PMID- 25111457 TI - Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults. AB - BACKGROUND: Traumatic brain injury (TBI) contributes to a substantial number of deaths and cases of disability. Despite well-established experimental models and years of carefully conducted research, a clinical therapeutic breakthrough in TBI has lagged. This may be due, in part, to the discrepancies between commonly used experimental models and clinical scenarios. METHOD: Secondary insults, such as hypotension and hypoxemia, have been well demonstrated as powerful determinants of outcomes from TBI. Despite the frequency of secondary insults in patients with TBI, they are rarely incorporated into most existing models of TBI. This review focuses on the combined injury models, especially coupled with systemic secondary insults, and aims to provide a new view to guiding future research endeavors in this field. RESULTS: A growing number of experimental models of TBI complicated by certain secondary insult have been gradually introduced and characterized. Correspondingly, the pathophysiological changes following combined injuries and the interactive effects of primary injury with secondary insults can be studied more in-depth. CONCLUSION: A more complete understanding of the interactions between the injured brain and secondary insults represents a potentially fruitful avenue that may increase the likelihood of developing effective therapies. Experimental models of TBI should not only attempt to model the focal or diffuse changes resulting from external forces, but also integrate, when appropriate, secondary insults reminiscent of human situations. PMID- 25111458 TI - Effects of acute exposure to the non-steroidal anti-inflammatory drug ibuprofen on the developing North American Bullfrog (Rana catesbeiana) tadpole. AB - A variety of pharmaceutical chemicals can represent constituents of municipal effluent outflows that are dispersed into aquatic receiving environments worldwide. Increasingly, there is concern as to the potential of such bioactive substances to interact with wildlife species at sensitive life stages and affect their biology. Using a combination of DNA microarray, quantitative real-time polymerase chain reaction, and quantitative nuclease protection assays, we assessed the ability of sub-lethal and environmentally relevant concentrations of ibuprofen (IBF), a non-steroidal anti-inflammatory agent and prevalent environmental contaminant, to function as a disruptor of endocrine-mediated post embryonic development of the frog. While the LC50 of IBF for pre-metamorphic Rana catesbeiana tadpoles is 41.5 mg/L (95% confidence interval: 32.3-53.5 mg/L), exposure to concentrations in the ppb range elicited molecular responses both in vivo and in organ culture. A nominal concentration of 15 MUg/L IBF (actual = 13.7 MUg/L) altered the abundance of 26 mRNA transcripts within the liver of exposed pre-metamorphic R. catesbeiana tadpoles within 6 d. IBF-treated animals demonstrated subsequent disruption of thyroid hormone-mediated reprogramming in the liver transcriptome affecting constituents of several metabolic, developmental, and signaling pathways. Cultured tadpole tail fin treated with IBF for 48 h also demonstrated altered mRNA levels at drug concentrations as low as 1.5 MUg/L. These observations raise the possibility that IBF may alter the post embryonic development of anuran species in freshwater environs, where IBF is a persistent or seasonal pollutant. PMID- 25111459 TI - Folate testing: time to retire your VCR. PMID- 25111460 TI - Oxidized low density lipoprotein increases acetylcholinesterase activity correlating with reactive oxygen species production. AB - Hyperlipidemia, low density lipoproteins (LDL) and their oxidized forms, and oxidative stress are suspected to be a key combination in the onset of AD and acetylcholinesterase (AChE) plays a part in this pathology. The present study aimed to link these parameters using differentiated SH-SY5Y human neuroblastoma cells in culture. Both mildly and fully oxidized human LDL (mox- and fox-LDL), but not native (non-oxidized) LDL were cytotoxic in dose- and time-dependent patterns and this was accompanied by an increased production of intracellular reactive oxygen species (ROS). Oxidized LDL (10-200 MUg/mL) augmented AChE activity after 4 and 24h treatments, respectively while the native LDL was without effect. The increased AChE with oxidized LDLs was accompanied by a proportionate increase in intracellular ROS formation (R=0.904). These findings support the notion that oxidized LDLs are cytotoxic and that their action on AChE may reduce central cholinergic transmission in AD and affirm AChE as a continued rational for anticholinesterase therapy but in conjunction with antioxidant/antihyperlipidemic cotreatments. PMID- 25111461 TI - miR-129-1-3p promote BGC-823 cell proliferation by targeting PDCD2. AB - MicroRNAs (miRNAs) are the class of small noncoding RNAs, and play an important role in the regulation of gene expression at the posttranscriptional level. In this study, we explored the effect of miR-129-1-3p on the growth and cell cycle of human gastric cancer cell line BGC-823. The miR-129-1-3p mimics or inhibitors were transfected into the BGC-823 cell line, and the cell cycle and cell growth was measured by flow cytometry and real-time cell analyzer, respectively. The possible targets of miR-129-1-3p were analyzed by quantitative real time-PCR (QRT PCR), Western blotting and Luciferase reporter assay. The results showed that miR 129-1-3p could promote the growth and cell cycle of BGC-823 cells. Although protein expression of programmed cell death 2 (PDCD2) was not changed with miR 129-1-3p, QRT-PCR showed that expression of PDCD2 mRNA was negatively related to the miR-129-1-3p. Luciferase reporter assay revealed that PDCD2 is one of the targets of miR-129-1-3p. Our results indicated that miR-129-1-3p might promote proliferation of BGC-823 cells by targeting PDCD2. PMID- 25111462 TI - Impact of several pre-treatments on the extraction of phenolic compounds in winegrape varieties with different anthocyanin profiles and skin mechanical properties. AB - This study was performed to evaluate and compare the effects of different pre treatments of whole grape berries (freezing with dry ice or in a cold room, steam blanching with different exposure times, and microwave heating with different exposure times and microwave power density) on total content of some phenolic compounds and the composition of individual anthocyanins released into the pulp during the treatment and those extracted during the maceration step. Two red winegrape varieties with different proportions of di- and trisubstituted anthocyanins were used (Nebbiolo and Barbera, respectively). Pulp-extracted anthocyanins were more significantly influenced by the pre-treatment. The results highlighted that freezing with dry ice, followed by freezing in a cold room and steam blanching for 5 min, have a great potential from an industrial point of view. They facilitated the extraction of anthocyanins in the must prior to maceration, when compared with the control samples, increasing their total content (+37.8-83.6%), and modifying the anthocyanin profile through the enrichment in the most stable compounds (+2.8-6.6% malvidin derivatives) to the detriment of others more prone to oxidation (-0.8-11.0% cyanidin derivatives). In Nebbiolo winegrapes, an improved extraction of low- and high-molecular weight flavanols into the pulp was also observed (+60.4-73.4%). Significant relationships between the phenolic composition of treated berries and the corresponding skin mechanical properties were also studied, but they were variety dependent. Discriminant analysis permitted a correct classification of the samples according to the variety and pre-treatment. PMID- 25111463 TI - Breaking immune tolerance by targeting CD25+ regulatory T cells is essential for the anti-tumor effect of the CTLA-4 blockade in an HLA-DR transgenic mouse model of prostate cancer. AB - INTRODUCTION: Recent studies suggest that the cancer immunotherapy based on the blockade of the CTLA-4-mediated inhibitory pathway is efficacious only in select populations, predominantly for immunogenic tumors or when delivered in combination with modalities that can break immunologic tolerance to tumor antigens. METHODS: We studied the effect of CD25+ cell depletion and CTLA-4 blockade on the growth of Transgenic Mouse Adenocarcinoma of Prostate (TRAMP)-PSA tumor cells in DR2bxPSA F1 mice. In these mice, immunological tolerance to PSA was established in a context of the HLA-DRB1*1501(DR2b) allele. RESULTS: In our model, single administration of anti-CD25 antibody prior to tumor inoculation significantly increased IFN-gamma production in response to the CD8 T cell epitope PSA65-73 , and delayed TRAMP-PSA tumor growth compared to mice treated with isotype control antibodies. In contrast, the anti-tumor effect of the anti CTLA-4 antibody as a monotherapy was marginal. The combinatory treatment with anti-CD25/anti-CTLA-4 antibodies significantly enhanced anti-tumor immunity and caused more profound delay in tumor growth compared to each treatment alone. The proportion of tumor-free animals was higher in the group that received combination treatment (21%) compared to other groups (2-7%). The enhanced anti tumor immunity in response to the CD25 depletion or CTLA-4 blockade was only seen in the immunogenic TRAMP-PSA tumor model, whereas the effect was completely absent in mice bearing poorly immunogenic TRAMP-C1 tumors. DISCUSSION: Our data suggest that breaking immunological tolerance to "self" antigens is essential for the therapeutic effect of CTLA-4 blockade. Such combinatory treatment may be a promising approach for prostate cancer immunotherapy. PMID- 25111464 TI - School climate, family structure, and academic achievement: a study of moderation effects. AB - School climate has been lauded for its relationship to a host of desirable academic, behavioral, and social-emotional outcomes for youth. The present study tested the hypothesis that school climate counteracts youths' home-school risk by examining the moderating effects of students' school climate perceptions on the relationship between family structure (i.e., two-parent, one-parent, foster-care, and homeless households), and academic performance (i.e., self-reported [grade point average] GPA). The present sample consisted of 902 California public high schools, including responses from over 490,000 students in Grades 9 and 11. Results indicated that, regardless of family structure, students with more positive school climate perceptions self-reported higher GPAs. Youths with two parent, one-parent, and homeless family structures displayed stepwise, linear improvements in self-reported GPA as perceptions of climate improved. Foster-care students' positive school climate perceptions had a weaker effect on their self reported GPA compared with students living in other family structures. A unique curvilinear trend was found for homeless students, as the relationship between their school climate perceptions and self-reported GPA was stronger at lower levels. Overall, the moderation effect of positive school climate perceptions on self-reported GPA was strongest for homeless youth and youth from one-parent homes, suggesting that school climate has a protective effect for students living in these family structures. A protective effect was not found for youth in foster care. Implications for research and practice are discussed. PMID- 25111465 TI - Efficacy of the Social Skills Improvement System Classwide Intervention Program (SSIS-CIP) primary version. AB - A multisite cluster randomized trial was conducted to examine the effects of the Social Skills Improvement System Classwide Intervention Program (SSIS-CIP; Elliott & Gresham, 2007) on students' classroom social behavior. The final sample included 432 students across 38 second grade classrooms. Social skills and problem behaviors were measured via the SSIS rating scale for all participants, and direct observations were completed for a subsample of participants within each classroom. Results indicated that the SSIS-CIP demonstrated positive effects on teacher ratings of participants' social skills and internalizing behaviors, with the greatest changes occurring in classrooms with students who exhibited lower skill proficiency prior to implementation. Statistically significant differences were not observed between treatment and control participants on teacher ratings of externalizing problem behaviors or direct observation. PMID- 25111466 TI - Examination of the change in latent statuses in bullying behaviors across time. AB - Involvement in bullying and victimization has been mostly studied using cross sectional data from 1 time point. As such, much of our understanding of bullying and victimization has not captured the dynamic experiences of youth over time. To examine the change of latent statuses in bullying and victimization, we applied latent transition analysis examining self-reported bullying involvement from 1,180 students in 5th through 9th grades across 3 time points. We identified unobserved heterogeneous subgroups (i.e., latent statuses) and investigated how students transition between the unobserved subgroups over time. For victimization, 4 latent statuses were identified: frequent victim (11.23%), occasional traditional victim (28.86%), occasional cyber and traditional victim (10.34%), and infrequent victim (49.57%). For bullying behavior, 3 latent statuses were identified: frequent perpetrator (5.12%), occasional verbal/relational perpetrator (26.04%), and infrequent perpetrator (68.84%). The characteristics of the transitions were examined. The multiple-group effects of gender, grade, and first language learned on transitions across statuses were also investigated. The infrequent victim and infrequent perpetrator groups were the most stable, and the frequent victim and frequent perpetrator groups were the least stable. These findings suggest instability in perpetration and victimization over time, as well as significant changes, especially during school transition years. Findings suggest that school-based interventions need to address the heterogeneity in perpetrator and victim experiences in adolescence. PMID- 25111467 TI - Psychosocial functioning of bullied youth who adopt versus deny the bully-victim label. AB - This study addressed a need for research on the association between adopting or denying the label of bully victim and students' psychosocial functioning. Participants were 1,063 students in Grades 5, 7, and 9 in a school district in the northeastern United States. Students were grouped based on their pattern of responses to (a) the California Bully Victimization Scale (Felix et al., 2011), which does not use the term "bully," but includes behavioral items assessing frequency of peer victimization and whether or not that victimization involved any perceived power disadvantage, and (b) the Olweus Bully/Victim Questionnaire (Solberg & Olweus, 2003; Solberg, Olweus, & Endresen, 2007), which queries self identification as a bully victim. We compared groups using a series of planned comparisons with ANOVA on self-reported emotional distress and withdrawal, behavioral reactivity and conduct problems, and prosocial behavior and peer competence, as measured by the Strengths and Difficulties Questionnaire (Goodman, 1997). Results revealed complexities regarding the experience of bullying. The perception of a power difference and having been bullied both related to psychosocial functioning in an interactive way, suggesting that both are important to query. Moreover, students who labeled themselves as victims of bullying reported poorer psychosocial functioning than those who had the experience of being bullied but did not adopt that label. PMID- 25111468 TI - Identifying emotional and behavioral risk among gifted and nongifted children: A multi-gate, multi-informant approach. AB - The purpose of the current investigation was to compare 1,206 gifted and nongifted elementary students on the identification of emotional and behavioral risk (EBR) as rated by teachers and parents using a multigate, multi-informant approach to assessment. The Parent and Teacher Behavioral Assessment System for Children, Second Edition (BASC-2) and the Behavioral and Emotional Screening System were used to assess behavioral functioning as rated by teachers and parents. There were significant differences between the number of gifted and nongifted children demonstrating emotional and behavioral risk, with parents and teachers identifying a higher number of boys and nongifted children as at risk. Among children demonstrating EBR, gifted children demonstrated elevated internalizing behaviors as rated by parents. Gifted students demonstrated higher academic performance regardless of risk level, suggesting higher cognitive abilities may be one of several protective factors that serve to attenuate the development of other social, emotional, or behavioral concerns. Implications for practice and future research needs are discussed. PMID- 25111469 TI - A comparison of measures to screen for social, emotional, and behavioral risk. AB - The purpose of this study was to examine the relation between teacher-implemented screening measures used to identify social, emotional, and behavioral risk. To this end, 5 screening options were evaluated: (a) Direct Behavior Rating - Single Item Scales (DBR-SIS), (b) Social Skills Improvement System - Performance Screening Guide (SSiS), (c) Behavioral and Emotional Screening System - Teacher Form (BESS), (d) Office discipline referrals (ODRs), and (e) School nomination methods. The sample included 1974 students who were assessed tri-annually by their teachers (52% female, 93% non-Hispanic, 81% white). Findings indicated that teacher ratings using standardized rating measures (DBR-SIS, BESS, and SSiS) resulted in a larger proportion of students identified at-risk than ODRs or school nomination methods. Further, risk identification varied by screening option, such that a large percentage of students were inconsistently identified depending on the measure used. Results further indicated weak to strong correlations between screening options. The relation between broad behavioral indicators and mental health screening was also explored by examining classification accuracy indices. Teacher ratings using DBR-SIS and SSiS correctly identified between 81% and 91% of the sample as at-risk using the BESS as a criterion. As less conservative measures of risk, DBR-SIS and SSiS identified more students as at-risk relative to other options. Results highlight the importance of considering the aims of the assessment when selecting broad screening measures to identify students in need of additional support. PMID- 25111470 TI - Characteristics of the default mode functional connectivity in normal ageing and Alzheimer's disease using resting state fMRI with a combined approach of entropy based and graph theoretical measurements. AB - Cognitive decline in normal ageing and Alzheimer's disease (AD) emerges from functional disruption in the coordination of large-scale brain systems sustaining cognition. Integrity of these systems can be examined by correlation methods based on analysis of resting state functional magnetic resonance imaging (fMRI). Here we investigate functional connectivity within the default mode network (DMN) in normal ageing and AD using resting state fMRI. Images from young and elderly controls, and patients with AD were processed using spatial independent component analysis to identify the DMN. Functional connectivity was quantified using integration and indices derived from graph theory. Four DMN sub-systems were identified: Frontal (medial and superior), parietal (precuneus-posterior cingulate, lateral parietal), temporal (medial temporal), and hippocampal (bilateral). There was a decrease in antero-posterior interactions (lower global efficiency), but increased interactions within the frontal and parietal sub systems (higher local clustering) in elderly compared to young controls. This decreased antero-posterior integration was more pronounced in AD patients compared to elderly controls, particularly in the precuneus-posterior cingulate region. Conjoint knowledge of integration measures and graph indices in the same data helps in the interpretation of functional connectivity results, as comprehension of one measure improves with understanding of the other. The approach allows for complete characterisation of connectivity changes and could be applied to other resting state networks and different pathologies. PMID- 25111471 TI - Optical Coherence Tomography angiography reveals laminar microvascular hemodynamics in the rat somatosensory cortex during activation. AB - The BOLD (blood-oxygen-level dependent) fMRI (functional Magnetic Resonance Imaging) signal is shaped, in part, by changes in red blood cell (RBC) content and flow across vascular compartments over time. These complex dynamics have been challenging to characterize directly due to a lack of appropriate imaging modalities. In this study, making use of infrared light scattering from RBCs, depth-resolved Optical Coherence Tomography (OCT) angiography was applied to image laminar functional hyperemia in the rat somatosensory cortex. After defining and validating depth-specific metrics for changes in RBC content and speed, laminar hemodynamic responses in microvasculature up to cortical depths of >1mm were measured during a forepaw stimulus. The results provide a comprehensive picture of when and where changes in RBC content and speed occur during and immediately following cortical activation. In summary, the earliest and largest microvascular RBC content changes occurred in the middle cortical layers, while post-stimulus undershoots were most prominent superficially. These laminar variations in positive and negative responses paralleled known distributions of excitatory and inhibitory synapses, suggesting neuronal underpinnings. Additionally, the RBC speed response consistently returned to baseline more promptly than RBC content after the stimulus across cortical layers, supporting a "flow-volume mismatch" of hemodynamic origin. PMID- 25111473 TI - Multi-label segmentation of white matter structures: application to neonatal brains. AB - Accurate and consistent segmentation of brain white matter bundles at neonatal stage plays an important role in understanding brain development and detecting white matter abnormalities for the prediction of psychiatric disorders. Due to the complexity of white matter anatomy and the spatial resolution of diffusion weighted MR imaging, multiple fiber bundles can pass through one voxel. The goal of this study is to assign one or multiple anatomical labels of white matter bundles to each voxel to reflect complex white matter anatomy of the neonatal brain. For this, we develop a supervised multi-label k-nearest neighbor (ML-kNN) classification algorithm in Riemannian diffusion tensor spaces. Our ML-kNN considers diffusion tensors lying on the Log-Euclidean Riemannian manifold of symmetric positive definite (SPD) matrices and their corresponding vector space as feature space. The ML-kNN utilizes the maximum a posteriori (MAP) principle to make the prediction of white matter labels by reasoning with the labeling information derived from the neighbors without assuming any probabilistic distribution of the features. We show that our approach automatically learns the number of white matter bundles at a location and provides anatomical annotation of the neonatal white matter. In addition, our approach also provides the binary mask for individual white matter bundles to facilitate tract-based statistical analysis in clinical studies. We apply this method to automatically segment 13 white matter bundles of the neonatal brain and examine the segmentation accuracy against semi-manual labels derived from tractography. PMID- 25111472 TI - Guiding functional connectivity estimation by structural connectivity in MEG: an application to discrimination of conditions of mild cognitive impairment. AB - Whole brain resting state connectivity is a promising biomarker that might help to obtain an early diagnosis in many neurological diseases, such as dementia. Inferring resting-state connectivity is often based on correlations, which are sensitive to indirect connections, leading to an inaccurate representation of the real backbone of the network. The precision matrix is a better representation for whole brain connectivity, as it considers only direct connections. The network structure can be estimated using the graphical lasso (GL), which achieves sparsity through l1-regularization on the precision matrix. In this paper, we propose a structural connectivity adaptive version of the GL, where weaker anatomical connections are represented as stronger penalties on the corresponding functional connections. We applied beamformer source reconstruction to the resting state MEG recordings of 81 subjects, where 29 were healthy controls, 22 were single-domain amnestic Mild Cognitive Impaired (MCI), and 30 were multiple domain amnestic MCI. An atlas-based anatomical parcellation of 66 regions was obtained for each subject, and time series were assigned to each of the regions. The fiber densities between the regions, obtained with deterministic tractography from diffusion-weighted MRI, were used to define the anatomical connectivity. Precision matrices were obtained with the region specific time series in five different frequency bands. We compared our method with the traditional GL and a functional adaptive version of the GL, in terms of log-likelihood and classification accuracies between the three groups. We conclude that introducing an anatomical prior improves the expressivity of the model and, in most cases, leads to a better classification between groups. PMID- 25111475 TI - The NOACs (novel oral anticoagulants) have landed! PMID- 25111476 TI - Unravelling immune alterations in schizophrenia: can DNA methylation provide clues? PMID- 25111477 TI - Pathogenesis of CpG island methylator phenotype-positive colorectal cancers: role of genetic alteration and colonic flora. PMID- 25111474 TI - Threat-related learning relies on distinct dorsal prefrontal cortex network connectivity. AB - Conditioned changes in the emotional response to threat (e.g. aversive unconditioned stimulus; UCS) are mediated in part by the prefrontal cortex (PFC). Unpredictable threats elicit large emotional responses, while the response is diminished when the threat is predictable. A better understanding of how PFC connectivity to other brain regions varies with threat predictability would provide important insights into the neural processes that mediate conditioned diminution of the emotional response to threat. The present study examined brain connectivity during predictable and unpredictable threat exposure using a fear conditioning paradigm (previously published in Wood et al., 2012) in which unconditioned functional magnetic resonance imaging data were reanalyzed to assess effective connectivity. Granger causality analysis was performed using the time series data from 15 activated regions of interest after hemodynamic deconvolution, to determine regional effective connectivity. In addition, connectivity path weights were correlated with trait anxiety measures to assess the relationship between negative affect and brain connectivity. Results indicate the dorsomedial PFC (dmPFC) serves as a neural hub that influences activity in other brain regions when threats are unpredictable. In contrast, the dorsolateral PFC (dlPFC) serves as a neural hub that influences the activity of other brain regions when threats are predictable. These findings are consistent with the view that the dmPFC coordinates brain activity to take action, perhaps in a reactive manner, when an unpredicted threat is encountered, while the dlPFC coordinates brain regions to take action, in what may be a more proactive manner, to respond to predictable threats. Further, dlPFC connectivity to other brain regions (e.g. ventromedial PFC, amygdala, and insula) varied with negative affect (i.e. trait anxiety) when the UCS was predictable, suggesting that stronger connectivity may be required for emotion regulation in individuals with higher levels of negative affect. PMID- 25111478 TI - Epigenetic traits of testicular cancer: from primordial germ cells to germ cell tumors. PMID- 25111480 TI - Remodeling and spacing factor 1 (RSF1): a rising star in DNA repair. PMID- 25111481 TI - Specific inhibition of DNMT1/CFP1 reduces cancer phenotypes and enhances chemotherapy effectiveness. AB - AIM: DNA methylation is a fundamental biologic process of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantages. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention. MATERIALS & METHODS: To develop a new generation of DNMT inhibitor, we analyzed the ability of peptides to selectively inhibit certain DNMT1-incuding complexes. RESULTS: Our study demonstrates that the disruption of DNMT1/CFP1-including complexes increases the efficiency of chemotherapeutic treatment on established tumors in mice. CONCLUSION: Our data opens a promising and innovative alternative to the development of DNMT inhibitors. PMID- 25111482 TI - The KDM5 family of histone demethylases as targets in oncology drug discovery. AB - There is growing evidence for a causal role of the KDM5 family of histone demethylases in human cancer. In particular, KDM5A (JARID1A/RBP2) and KDM5B (JARID1B/PLU1) contribute to cancer cell proliferation, reduce the expression of tumor suppressor genes, promote the development of drug tolerance and maintain tumor-initiating cells. KDM5 enzymes remove tri- and di-methylations of lysine 4 of histone H3 - modifications that occur at the start site of transcription in actively transcribed genes. However, the importance of the histone demethylase activity of KDM5 proteins for cancer cells has not been resolved so far. The currently available approaches suppress or remove the targeted proteins and thereby affect their putative functions as structural components and recruitment factors for other chromatin-associated proteins. Therefore, the development of specific enzymatic inhibitors for KDM5 will promote our understanding of the biological role of their catalytic activity and yield potential novel anticancer therapeutics. PMID- 25111483 TI - Epigenetic modifications as novel therapeutic targets for Huntington's disease. AB - Huntington's disease is a late-onset, autosomal dominant neurodegenerative disorder characterized by motor, cognitive and psychiatric symptomatology. The earliest stage of Huntington's disease is marked by alterations in gene expression, which partially results from dysregulated epigenetic modifications. In past decades, altered epigenetic markers including histone modifications (acetylation, methylation, ubiquitylation and phosphorylation) and DNA modifications (cytosine methylation and hydroxymethylation) have been reported as important epigenetic features in patients and multiple animal models of Huntington's disease. Drugs aimed to correct some of those alterations have shown promise in treating Huntington's disease. This article discusses the field of epigenetics for potential Huntington's disease interventions and presents the most recent findings in this area. PMID- 25111484 TI - Using epigenomic studies in monozygotic twins to improve our understanding of cancer. AB - Cancer is a set of diseases that exhibit not only genetic mutations but also a profoundly distorted epigenetic landscape. Over the last two decades, great advances have been made in identifying these alterations and their importance in the initiation and progression of cancer. Epigenetic changes can be seen from the very early stages in tumorigenesis and dysregulation of the epigenome has an increasingly acknowledged pathogenic role. Epigenomic twin studies have great potential to contribute to our understanding of complex diseases, such as cancer. This is because the use of monozygotic twins discordant for cancer enables epigenetic variation analysis without the confounding influence of the constitutive genetic background, age or cohort effects. It therefore allows the identification of susceptibility loci that may be sensitive to modification by the environment. These studies into cancer etiology will potentially lead to robust epigenetic markers for the detection and risk assessment of cancer. PMID- 25111485 TI - DNA methylation markers for early detection of women's cancer: promise and challenges. AB - Breast, ovarian and endometrial cancers cause significant morbidity and mortality. Despite the presence of existing screening, diagnostic and treatment modalities, they continue to pose considerable unsolved challenges. Overdiagnosis is a growing problem in breast cancer screening and neither screening nor early diagnosis of ovarian or endometrial cancer is currently possible. Moreover, treatment of the diversity of these cancers presenting in the clinic is not sufficiently personalized at present. Recent technological advances, including reduced representation bisulfite sequencing, methylation arrays, digital PCR, next-generation sequencing and advanced statistical data analysis, enable the analysis of methylation patterns in cell-free tumor DNA in serum/plasma. Ongoing work is bringing these methods together for the analysis of samples from large clinical trials, which have been collected well in advance of cancer diagnosis. These efforts pave the way for the development of a noninvasive method that would enable us to overcome existing challenges to personalized medicine. PMID- 25111487 TI - EZH2 as a potential target in cancer therapy. AB - Over the last several years, dysregulation of epigenetic mechanisms including DNA and histone methylation has been recognized as a hallmark of cancer. Alterations of epigenetic regulators themselves, including the histone lysine methyltransferase EZH2, have been reported in numerous cancer types. With the discovery of small molecule inhibitors of EZH2, we can now begin to evaluate EZH2 as a therapeutic target in cancer. This article will provide an overview of the dysregulation of EZH2 in cancer, possible mechanisms for inhibition of EZH2 activity, and the preclinical activity of currently available EZH2 inhibitors. PMID- 25111488 TI - Active DNA demethylation of the vertebrate genomes by DNA methyltransferases: deaminase, dehydroxymethylase or demethylase? AB - Vertebrate DNA methyltransferases (DNMTs) have been thought to primarily function to covalently add a methyl group to the 5-position of cytosine. However, recent discovery of the DNA demethylation and dehydroxymethylation activities of DNMTs in vitro suggest new routes to complete the dynamic cycle of DNA methylation demethylation of the vertebrate genomes. The in vitro reaction conditions suggest that vertebrate DNMTs can switch from DNA methylases to DNA dehydroxymethylases under oxidative stress and to DNA demethylases in the presence of calcium ion under nonreducing conditions. These environmental parameters provide clues regarding the choices in vivo of DNMT activities utilized in different physiological systems. In particular, the nature of these parameters suggest that the DNA demethylation and dehydroxymethylation activities of the vertebrate DNMTs play essential roles in multiple biological processes including early embryo development, regulation of neuronal plasticity, tumorigenesis and hormone regulated transcription. PMID- 25111486 TI - Functions of SAGA in development and disease. AB - Precise regulation of gene expression programs during embryo development requires cooperation between transcriptional factors and histone-modifying enzymes, such as the Gcn5 histone acetyltransferase. Gcn5 functions within a multi-subunit complex, called SAGA, that is recruited to specific genes through interactions with sequence-specific DNA-binding proteins to aid in gene activation. Although the transcriptional programs regulated by SAGA in embryos are not well defined, deletion of either Gcn5 or USP22, the catalytic subunit of a deubiquitinase module in SAGA, leads to early embryonic lethality. Here, we review the known functions of Gcn5, USP22 and associated proteins during development and discuss how these functions might be related to human disease states, including cancer and neurodegenerative diseases. PMID- 25111490 TI - Thermal conductivity of graphene laminate. AB - We have investigated thermal conductivity of graphene laminate films deposited on polyethylene terephthalate substrates. Two types of graphene laminate were studied, as deposited and compressed, in order to determine the physical parameters affecting the heat conduction the most. The measurements were performed using the optothermal Raman technique and a set of suspended samples with the graphene laminate thickness from 9 to 44 MUm. The thermal conductivity of graphene laminate was found to be in the range from 40 to 90 W/mK at room temperature. It was found unexpectedly that the average size and the alignment of graphene flakes are more important parameters defining the heat conduction than the mass density of the graphene laminate. The thermal conductivity scales up linearly with the average graphene flake size in both uncompressed and compressed laminates. The compressed laminates have higher thermal conductivity for the same average flake size owing to better flake alignment. Coating plastic materials with thin graphene laminate films that have up to 600* higher thermal conductivity than plastics may have important practical implications. PMID- 25111489 TI - Multicellular architecture of malignant breast epithelia influences mechanics. AB - Cell-matrix and cell-cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In this study, we investigated the influence of the multicellular tissue architecture on mechanical properties of the epithelial component of the mammary acinus. Using creep compression tests on multicellular breast epithelial structures, we found that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than normal hollow acini (MCF10A) by 60%. This difference depended on structural changes in the pre-malignant acini, as neither single cells nor normal multicellular acini tested before lumen formation exhibited these differences. To understand these differences, we simulated the deformation of the acini with different multicellular architectures and calculated their mechanical properties; our results suggest that lumen filling alone can explain the experimentally observed stiffness increase. We also simulated a single contracting cell in different multicellular architectures and found that lumen filling led to a 20% increase in the "perceived stiffness" of a single contracting cell independent of any changes to matrix mechanics. Our results suggest that lumen filling in carcinogenesis alters the mechanical microenvironment in multicellular epithelial structures, a phenotype that may cause downstream disruptions to mechanosensing. PMID- 25111491 TI - Editorial: European Symposium on BioPolymers. PMID- 25111492 TI - Minocycline encapsulated chitosan nanoparticles for central antinociceptive activity. AB - The purpose of the study is to explore the central anti-nociceptive activity of brain targeted nanoparticles (NP) of minocycline hydrochloride (MH). The NP were formulated using the modified ionotropic gelation method (MHNP) and were coated with Tween 80 (T80) to target them to brain (cMHNP). The formulated nanoparticles have already been characterized for particle size, zeta potential, drug entrapment efficiency and in vitro drug release. The nanoparticles were then evaluated for pharmacodynamic activity using thermal methods. The pure drug and the formulation, MHNP were not able to show a statistically significant central analgesic activity. cMHNP on the other hand evidenced a significant central analgesic activity. Animal models evidenced that brain targeted nanoparticles may be utilized for effective delivery of central anti-nociceptive effect of MH. Further clinical studies are required to explore the activity for mankind. PMID- 25111493 TI - Extraction optimization of polysaccharide from Zanthoxylum bungeanum using RSM and its antioxidant activity. AB - Polysaccharide prepared from pericarp of Zanthoxylum bungeanum was proved to possess excellent antioxidant activities in vitro by using reducing ferric iron power, DPPH radical scavenging activity, chelating ferrous iron capacity, and hydroxyl radical scavenging activity assays in the present study. In those four antioxidant assay models, Z. bungeanum polysaccharide (ZBP) displayed prominent antioxidant activities with low EC50 values of 0.011, 0.021, 0.056 and 0.008 mg/mL, respectively. Moreover, the extraction process of ZBP was further optimized by response surface methodology combined with Box-Behnken design. The highest polysaccharide yield 13.96%, which agreed closely with the predicted yield 13.20%, was obtained under the optimal extraction conditions as follows: extraction temperature 89 degrees C, extraction time 3h, ratio of water volume (mL) to raw material weight (g) 29 (v/w), and extraction number two times. The present research not only provide theoretical basis for exploitation of natural polysaccharide antioxidants, but also establish the foundation of large-scale production and further system utilization of ZBP. PMID- 25111494 TI - Preparation of amidated derivatives of carboxymethylcellulose. AB - Carboxymethylcellulose (CMC) was selected as substrate for amidation based on previous results described for monocarboxy cellulose (MCC) with the aim to prepare highly substituted products. In comparison with MCC containing uronic carboxyl groups at C-6 position, O-carboxymethyl groups in CMC should be more accessible for reagents because they are more distant from the polysaccharide chain. Two-step way of amidation was based on the esterification of CMC carboxyls by reaction with methanol and further amino-de-alkoxylation (aminolysis) of the obtained methyl ester with amidation reagents (n-alkylamines, hydrazine and hydroxylamine). Purity and substitution degree of the products were monitored by the vibration spectroscopic methods (FTIR and Raman) and organic elemental analysis. Analytical methods confirmed the preparation of highly or moderately substituted N-alkylamides, hydrazide and hydroxamic acid of CMC. PMID- 25111495 TI - Metal ion-induced alginate-locust bean gum IPN microspheres for sustained oral delivery of aceclofenac. AB - The alginate microspheres represent a useful tool for sustained oral delivery of drugs but exhibit several problems associated with the stability and rapid release of drugs at higher pH values. To overcome these drawbacks, alginate locust bean gum (LBG) interpenetrating microspheres were prepared by calcium ion (Ca(+2)) induced ionotropic gelation technique for prolonged release of aceclofenac. The drug entrapment efficiency of these microspheres was found to be 59-93%. The microspheres lied in the size range of 406-684MUm. Scanning electron microscopy revealed spherical shape of the microspheres. No drug-polymer interaction was evident after infrared spectroscopy analysis. The microspheres provided sustained release of aceclofenac in phosphate buffer solution (pH 6.8) over a period of 8h. The drug release data were fitted into the Korsmeyer-Peppas model and the drug release was found to follow anomalous (non-Fickian) diffusion mechanism. Pharmacodynamic study of the microspheres showed a prolonged anti inflammatory activity in carrageenan-induced rat paw model following oral administration. PMID- 25111497 TI - A contact-imaging based microfluidic cytometer with machine-learning for single frame super-resolution processing. AB - Lensless microfluidic imaging with super-resolution processing has become a promising solution to miniaturize the conventional flow cytometer for point-of care applications. The previous multi-frame super-resolution processing system can improve resolution but has limited cell flow rate and hence low throughput when capturing multiple subpixel-shifted cell images. This paper introduces a single-frame super-resolution processing with on-line machine-learning for contact images of cells. A corresponding contact-imaging based microfluidic cytometer prototype is demonstrated for cell recognition and counting. Compared with commercial flow cytometer, less than 8% error is observed for absolute number of microbeads; and 0.10 coefficient of variation is observed for cell ratio of mixed RBC and HepG2 cells in solution. PMID- 25111496 TI - Role for heat shock protein 90alpha in the proliferation and migration of HaCaT cells and in the deep second-degree burn wound healing in mice. AB - Inflammation, proliferation, and tissue remodeling are essential steps for wound healing. The hypoxic wound microenvironment promotes cell migration through a hypoxia--heat shock protein 90 alpha (Hsp90alpha)--low density lipoprotein receptor-related protein-1 (LRP-1) autocrine loop. To elucidate the role of this autocrine loop on burn wound healing, we investigated the expression profile of Hsp90alpha at the edge of burn wounds and found a transient increase in both mRNA and protein levels. Experiments performed with a human keratinocyte cell line- HaCaT also confirmed above results. 17-dimethylaminoethylamino 17demethoxygeldanamycin hydrochloride (17-DMAG), an Hsp90alpha inhibitor, was used to further evaluate the function of Hsp90alpha in wound healing. Consistently, topical application of Hsp90alpha in the early stage of deep second degree burn wounds led to reduced inflammation and increased tissue granulation, with a concomitant reduction in the size of the wound at each time point tested (p<0.05). Consequently, epidermal cells at the wound margin progressed more rapidly causing an expedited healing process. In conclusion, these results provided a rationale for the therapeutic effect of Hsp90alpha on the burn wound management. PMID- 25111498 TI - Enhanced fluorescence of gold nanoclusters composed of HAuCl4 and histidine by glutathione: glutathione detection and selective cancer cell imaging. AB - Glutathione (GSH) can significantly and selectively enhance the fluorescence intensity of Au nanoclusters (NCs) prepared by blending HAuCl4 and histidine in solution. The quantum yield of the Au NCs after adding GSH can reach above 10%. Besides, GSH capping shifts the excitation peak of Au NCs from ultraviolet (386 nm) to visible light (414 nm) and improves the stability of the Au NCs. The cytotoxicities of the Au NCs with and without GSH for normal lung cells (ATII) and cancerous lung cells (A549) are evaluated. The GSH-capped Au NCs have much less cytotoxicity to both normal and cancer cells, as compared to those without GSH. For Au NCs without GSH, less cytotoxicity is observed in cancer cells than in normal cells. In addtion, the Au NCs can selectively detect GSH over cysteine and homocysteine, the two biothiols which commonly exist in cells that can seriously affect GSH detection. Most importantly, Au NCs without GSH can selectively image the cancer cells, especially for the liver cancer cells whose GSH content is much higher than other cell types. This property makes the Au NCs a powerful probe to distinguish cancer cells from normal cells. PMID- 25111499 TI - Prognostic value of cardiac troponin in patients with chronic kidney disease without suspected acute coronary syndrome: a systematic review and meta-analysis. AB - BACKGROUND: Clinicians face uncertainty about the prognostic value of troponin testing in patients with chronic kidney disease (CKD) without suspected acute coronary syndrome (ACS). PURPOSE: To systematically review the literature on troponin testing in patients with CKD without ACS. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through May 2014. STUDY SELECTION: Studies examining elevated versus normal troponin levels in patients with CKD without ACS. DATA EXTRACTION: Paired reviewers selected articles for inclusion, extracted data, and graded strength of evidence (SOE). Meta-analyses were conducted when studies had sufficient homogeneity of key variables. DATA SYNTHESIS: Ninety-eight studies met inclusion criteria. Elevated troponin levels were associated with all-cause and cardiovascular mortality among patients receiving dialysis (moderate SOE). Pooled hazard ratios (HRs) for all-cause mortality from studies that adjusted for age and coronary artery disease or a risk equivalent were 3.0 (95% CI, 2.4 to 4.3) for troponin T and 2.7 (CI, 1.9 to 4.6) for troponin I. The pooled adjusted HRs for cardiovascular mortality were 3.3 (CI, 1.8 to 5.4) for troponin T and 4.2 (CI, 2.0 to 9.2) for troponin I. Findings were similar for patients with CKD who were not receiving dialysis, but there were fewer studies. No study tested treatment strategies by troponin cut points. LIMITATION: Studies were heterogeneous regarding assays, troponin cut points, covariate adjustment, and follow-up. CONCLUSION: In patients with CKD without suspected ACS, elevated troponin levels were associated with worse prognosis. Future studies should focus on whether this biomarker is more appropriate than clinical models for reclassifying risk of patients with CKD and whether such classification can help guide treatment in those at highest risk for death. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. PMID- 25111501 TI - Cryptosporidium species in humans and animals: current understanding and research needs. AB - Cryptosporidium is increasingly recognized as one of the major causes of moderate to severe diarrhoea in developing countries. With treatment options limited, control relies on knowledge of the biology and transmission of the members of the genus responsible for disease. Currently, 26 species are recognized as valid on the basis of morphological, biological and molecular data. Of the nearly 20 Cryptosporidium species and genotypes that have been reported in humans, Cryptosporidium hominis and Cryptosporidium parvum are responsible for the majority of infections. Livestock, particularly cattle, are one of the most important reservoirs of zoonotic infections. Domesticated and wild animals can each be infected with several Cryptosporidium species or genotypes that have only a narrow host range and therefore have no major public health significance. Recent advances in next-generation sequencing techniques will significantly improve our understanding of the taxonomy and transmission of Cryptosporidium species, and the investigation of outbreaks and monitoring of emerging and virulent subtypes. Important research gaps remain including a lack of subtyping tools for many Cryptosporidium species of public and veterinary health importance, and poor understanding of the genetic determinants of host specificity of Cryptosporidium species and impact of climate change on the transmission of Cryptosporidium. PMID- 25111500 TI - Neuromelanin magnetic resonance imaging reveals increased dopaminergic neuron activity in the substantia nigra of patients with schizophrenia. AB - PURPOSE: The dopamine hypothesis suggests that excessive dopamine release results in the symptoms of schizophrenia. The purpose of this study was to elucidate the dopaminergic and noradrenergic neurons using 3-T neuromelanin magnetic resonance imaging (MRI) in patients with schizophrenia and healthy control subjects. METHODS: We prospectively examined 52 patients with schizophrenia (M: F = 27?25, mean age, 35 years) and age- and sex-matched healthy controls. Using a 3T MRI unit, we obtained oblique T1-weighted axial images perpendicular to the brainstem. We measured the signal intensity and area for the substantia nigra (SNc), midbrain tegmentum, locus ceruleus (LC), and pons. We then calculated the contrast ratios (CR) for the SNc (CRSN) and LC (CRLC), which were compared between patients and healthy controls using unpaired t-tests. RESULTS: The SNc and LC were readily identified in both patients and healthy controls as areas with high signal intensities in the posterior part of the cerebral peduncle and in the upper pontine tegmentum. The CRSN values in patients were significantly higher than those in healthy controls (10.89+/-2.37 vs. 9.6+/-2.36, p<0.01). We observed no difference in the CRLC values between the patients and healthy controls (14.21+/-3.5 vs. 13.44+/-3.37, p = 0.25). Furthermore, there was no difference in area of the SNc and LC between schizophrenia patients and controls. CONCLUSIONS: Neuromelanin MRI might reveal increased signal intensity in the SNc of patients with schizophrenia. Our results indicate the presence of excessive dopamine products in the SNc of these patients. PMID- 25111502 TI - Oxygen-driven competition between low-dimensional structures of Sr3CoMO6 and Sr3CoMO7-delta with M = Ru, Ir. AB - We have realized a reversible structure transformation of one-dimensional 1D K4CdCl6-type Sr3CoMO6 with the Co(2+)/M(4+) cation ordering into the two dimensional 2D double layered Ruddlesden-Popper structure Sr3CoMO7-delta with a random distribution of Co and M (with M = Ru, Ir) upon increasing the partial oxygen pressure. The combined soft and hard X-ray absorption spectroscopy studies show that under transformation, Co and M cations were oxidized to Co(3+) and M(5+). During oxidation, high-spin Co(2+) in Sr3CoMO6 first transforms into high spin Co(3+) in oxygen-deficient Sr3CoMO7-delta, and then further transforms into low-spin Co(3+) in fully oxidized Sr3CoMO7 upon further increasing the partial pressure of oxygen. The 1D Sr3CoMO6 compound is magnetically ordered at low temperatures with the magnetic moments lying along the c-axis. Their alignment is parallel for Sr3CoRuO6 and antiparallel for Sr3CoIrO6. The 2D compounds reveal a spin-glass-like behavior related to the random distribution of magnetic cations in the structure. PMID- 25111503 TI - Cutaneous sensory function is not related to depression and anxiety in patients with chronic pruritus with dysesthetic subqualities. AB - The objective of this study was to examine the subgroup of patients with chronic pruritus with dysesthetic subqualities for the presence of psychiatric comorbidities and to evaluate whether anxiety and depression make a difference in perception of somatosensory stimuli in quantitative sensory testing (QST). Forty nine patients underwent routine diagnostics, a standardised QST testing battery, a psychosomatic evaluation for psychic comorbidities and filled out 2 questionnaires: the Patient Health Questionnaire for the assessment of depressive mood and the State Trait Anxiety Inventory. Twenty-seven (55.1%) of the sample had at least one psychiatric comorbid diagnosis. QST parameters were not correlated to anxiety and depression levels. We conclude that psychosomatic evaluation should become part of routine diagnostics of these patients in order to detect and treat psychiatric comorbidity. However, research on somatosensory aspects in these patients seems not to be affected by the levels of anxiety and depression. PMID- 25111505 TI - Synthesis and cytotoxic activity of 1-{3-[1-(5-organylsilylfuran-2-yl)silinan-1 yl]propyl}amines and some trimethylgermyl analogues. AB - New highly cytotoxic 1-{3-[1-(5-organylsilyl-furan-2-yl)silinan-1 yl]propyl}amines and some trimethylgermyl analogues (IC50 1-7 MUg mL(-1)) have been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N allylamines in the presence of Speier's catalyst. The effects of the silacycle, the element-organic substituent in position 5 of the furan ring, and the structure of the amine on the cytotoxicity of the new compounds have been studied. PMID- 25111504 TI - Inhibition of breast cancer resistance protein (ABCG2) in human myeloid dendritic cells induces potent tolerogenic functions during LPS stimulation. AB - Breast cancer resistance protein (ABCG2), a member of the ATP-binding cassette transporters has been identified as a major determinant of multidrug resistance (MDR) in cancer cells, but ABC transporter inhibition has limited therapeutic value in vivo. In this research, we demonstrated that inhibition of efflux transporters ABCG2 induced the generation of tolerogenic DCs from human peripheral blood myeloid DCs (mDCs). ABCG2 expression was present in mDCs and was further increased by LPS stimulation. Treatment of CD1c+ mDCs with an ABCG2 inhibitor, Ko143, during LPS stimulation caused increased production of IL-10 and decreased production of pro-inflammatory cytokines and decreased expression of CD83 and CD86. Moreover, inhibition of ABCG2 in monocyte-derived DCs (MDDCs) abrogated the up-regulation of co-stimulatory molecules and production of pro inflammatory cytokines in these cells in response to LPS. Furthermore, CD1c+ mDCs stimulated with LPS plus Ko143 inhibited the proliferation of allogeneic and superantigen-specific syngenic CD4+ T cells and promoted expansion of CD25+FOXP3+ regulatory T (Treg) cells in an IL-10-dependent fashion. These tolerogenic effects of ABCG2 inhibition could be abolished by ERK inhibition. Thus, we demonstrated that inhibition of ABCG2 in LPS-stimulated mDCs can potently induce tolerogenic potentials in these cells, providing crucial new information that could lead to development of better strategies to combat MDR cancer. PMID- 25111506 TI - Mitigating phototoxicity during multiphoton microscopy of live Drosophila embryos in the 1.0-1.2 um wavelength range. AB - Light-induced toxicity is a fundamental bottleneck in microscopic imaging of live embryos. In this article, after a review of photodamage mechanisms in cells and tissues, we assess photo-perturbation under illumination conditions relevant for point-scanning multiphoton imaging of live Drosophila embryos. We use third harmonic generation (THG) imaging of developmental processes in embryos excited by pulsed near-infrared light in the 1.0-1.2 um range. We study the influence of imaging rate, wavelength, and pulse duration on the short-term and long-term perturbation of development and define criteria for safe imaging. We show that under illumination conditions typical for multiphoton imaging, photodamage in this system arises through 2- and/or 3-photon absorption processes and in a cumulative manner. Based on this analysis, we derive general guidelines for improving the signal-to-damage ratio in two-photon (2PEF/SHG) or THG imaging by adjusting the pulse duration and/or the imaging rate. Finally, we report label free time-lapse 3D THG imaging of gastrulating Drosophila embryos with sampling appropriate for the visualisation of morphogenetic movements in wild-type and mutant embryos, and long-term multiharmonic (THG-SHG) imaging of development until hatching. PMID- 25111507 TI - Ethnicity is an independent determinant of age-specific PSA level: findings from a multiethnic Asian setting. AB - OBJECTIVES: To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting. MATERIALS AND METHODS: We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5alpha-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis. RESULTS: There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (<=4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05). CONCLUSION: These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population. PMID- 25111508 TI - Phytochemical study of Caulerpa racemosa (Forsk.) J. Agarth, an invading alga in the habitat of La Maddalena Archipelago. AB - Caulerpa racemosa is a marine Chlorophyta widely distributed in tropical areas, introduced into the Mediterranean Sea since 1990. It has been invading the Mediterranean Sea causing ecological problems. This invasive event can be considered as one of the most serious in the history of species introduced into the Mediterranean Sea, even if C. racemosa has not triggered as much attention as the famous 'killer alga' Caulerpa taxifolia. The aim of this work is to analyse phytochemically C. racemosa in the northern Sardinia area for secondary metabolites. Marine algae shows the molecular pattern of bis-indole alkaloids, sesquiterpenes, diterpenes and sterols. The intention is to expand phytochemical analysis in order to understand just how significant the anti-tumour, anti inflammatory and antinociceptive actions can be. PMID- 25111510 TI - Analysis of post-transplant chimerism by using a single amplification reaction of 38 Indel polymorphic loci. AB - In order to detect chimerism after allogeneic hematopoietic SCT (HSCT), several methods have been developed. In this study we describe the use of a set of insertion/deletion (Indel) polymorphic loci to determine the level of donor cell engraftment. We analyzed 50 DNA samples from patients who had undergone HSCT, and also several artificial chimeric samples created by mixing different DNA specimens from non-transplanted donors in various proportions. A specific set of 38 autosomic Indel polymorphisms were analyzed. For comparison purposes, a set of 15 short tandem repeats (STRs) were analyzed using the Identifiler Plus Amplification Kit. Our results suggest that Indel-based and STR-based procedures behave similarly in most cases. However, Indel analysis may provide additional information in some cases with a small minor chimeric component or when the presence of stutter bands complicates chimerism estimation. PMID- 25111509 TI - T helper subsets in allergic eye disease. AB - PURPOSE OF REVIEW: Ocular allergy is an IgE-mediated disease that results in inflammation of the conjunctiva and, in more severe cases, the cornea. This is driven by an immediate hypersensitivity response via mast cells, followed by a late phase response mediated by eosinophils both of which are indeed dependent on T helper (Th) lymphocyte activity. Here, we provide an update on Th subsets [Th1, Th2, Th17, and T regulatory (Treg)] and their relevance in ocular allergy. RECENT FINDINGS: Recent evidence in ocular allergy points to an involvement of other Th subsets, in addition to Th2. However, how these subsets are activated and their role in mediating the different clinical forms is poorly understood. Novel mouse models may facilitate addressing such unknowns, and future challenges will involve how to translate such findings into more effective and 'patho-specific' treatments. SUMMARY: Ocular allergy, especially in severe forms, involves subsets other than Th2. Th1 cells have been detected in mild and severe forms, and recent evidence points to a possible role for IL-17 in severe disease. Tregs, on the other hand, dampen pathogenic Th cell function and allergy immunotherapy is associated with Treg augmentation in disease management. Further understanding of Th biology is warranted and may lead to better therapies. PMID- 25111511 TI - Impact of pretransplant body mass index on the clinical outcome after allogeneic hematopoietic SCT. AB - To elucidate the impact of pretransplant body mass index (BMI) on the clinical outcome, we performed a retrospective study with registry data including a total of 12 050 patients (age ?18 years) who received allogeneic hematopoietic SCT (HSCT) between 2000 and 2010. Patients were stratified as follows: BMI<18.5 kg/m(2), Underweight, n=1791; 18.5?BMI<25, Normal, n=8444; 25?BMI<30, Overweight, n=1591; BMI?30, Obese, n=224. The median age was 45 years (range, 18-77). A multivariate analysis showed that the risk of relapse was significantly higher in the underweight group and lower in the overweight and obese groups compared with the normal group (hazard ratio (HR), 1.16, 0.86, and 0.74, respectively). The risk of GVHD was significantly higher in the overweight group compared with the normal group. The risk of non-relapse mortality (NRM) was significantly higher in the overweight and obese group compared with the normal group (HR 1.19 and HR 1.43, respectively). The probability of OS was lower in the underweight group compared with the normal group (HR 1.10, P=0.018). In conclusion, pretransplant BMI affected the risk of relapse and NRM after allogeneic HSCT. Underweight was a risk factor for poor OS because of an increased risk of relapse. Obesity was a risk factor for NRM. PMID- 25111512 TI - Identification of molecular and cytogenetic risk factors for unfavorable core binding factor-positive adult AML with post-remission treatment outcome analysis including transplantation. AB - Emerging molecular studies have identified a subgroup of patients with unfavorable core-binding factor-positive (CBF)-AML who should be treated by intensified post-remission treatments. We analyzed 264 adults with CBF-AML from 2002 to 2011, and focused on 206 patients who achieved CR after standard '3+7' induction chemotherapy. Patients who achieved CR with an available donor were treated with allogeneic hematopoietic SCT (allo-HSCT, n=115) and the rest were treated with autologous (auto) HSCT (n=72) or chemotherapy alone (n=19). OS was not significantly different between CBFbeta/MYH11 (n=62) and RUNX1/RUNX1T1 (n=144), and auto-HSCT showed favorable OS compared with allo-HSCT or chemotherapy alone. Cytogenetic analysis identified that inv(16) without trisomy had a favorable OS and t(8;21) with additional chromosomes had an unfavorable OS, but multivariate analysis revealed those were NS. Patients with c-kit mutation showed inferior OS. For transplanted patients, residual post-transplant CBF minimal residual disease quantitative PCR with higher WT1 expression at D+60 showed the worst OS with a higher incidence of relapse. Conclusively, we found that unfavorable CBF-AML can be defined with risk stratification using cytogenetic and molecular studies, and a careful risk-adapted treatment approach using frontline transplantation with novel therapies should be evaluated for this particular risk subgroup. PMID- 25111513 TI - BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA related SCT. AB - The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome analysis to investigate genetic variants-other than HLA class I and II-associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 beta-Thalassemic patients. We identified two single-nucleotide polymorphisms (SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong linkage disequilibrium between each other (R(2)=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P<0.00001 for BAT2 SNP rs11538264, and P<0.0001 for BAT3 SNP rs10484558), whereas the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs 2.6%, nominal P=1.15 * 10(-8); and adjusted P=0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent a novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT. PMID- 25111514 TI - Outcomes of stem cell transplant patients with acute respiratory failure requiring mechanical ventilation in the United States. AB - SCT indications and procedures are increasing worldwide. We sought to estimate the prevalence of acute respiratory failure (ARF) of any cause in hospitalized SCT patients, and assess the impact of invasive mechanical ventilation (IMV) on outcomes. We hypothesize that duration of IMV in such patients is an independent predictor of higher mortality. We performed a retrospective analysis of the largest all-payer hospitalization data set in the United States, Nationwide In patient Sample for years 2004-2010. Of the 101 462 SCT hospitalizations, 6074 (6%) developed ARF and were the final cohort. Type of SCT with ARF included autologous 1987 (32.7%), allogeneic 3467 (57.1%) and cord blood 655 (10.8%). Duration of IMV included <96 h (17.1%) and ?96 h (41.1%). Overall in-hospital mortality (IHM) was 50.6% (3075). Predictors of IHM were IMV <96 h (odds ratio=3.42 (2.44-4.79), P<0.0001) or IMV ?96 h (OR=4.61 (3.17-6.70), P<0.0001). Type of SCT, comorbid burden, gender, hospital-teaching status/bed size or insurance did not influence IHM. IMV ?96 h was associated with higher hospital charges (mean $762 515, 95% estimate 0.3991 (0.3123-0.4859), increase of $304 474, P<0.0001) and higher length of stay (mean 61.5 days, 95% estimate 0.2198 (0.1531-0.2866), increase of 13 days, P<0.0001). In conclusion, ARF in hospitalized SCT patients is not an uncommon occurrence and is associated with 50% mortality. Duration of IMV (?96 h) was an independent predictor of higher mortality rates. Hospital resource utilization was significant. PMID- 25111515 TI - Aerobic exercise capacity at long-term follow-up after paediatric allogeneic haematopoietic SCT. AB - Peak oxygen uptake (VO2peak), a measure of aerobic exercise capacity, predicts mortality and morbidity in healthy and diseased individuals. Our aim was to determine VO2peak years after paediatric allogeneic haematopoietic SCT (HSCT) and to identify associations with baseline patient and donor characteristics, transplantation factors, pulmonary function and self-reported sports activity. In this cross-sectional, population-based study, we measured VO2peak, spirometry and diffusion capacity of the lung (DLCO) 3-10 years post HSCT. Z-scores were calculated by reference values from healthy subjects. Self-reported hours of sports activity were obtained by interview. We included 63 patients (mean age (range) 14.4 (7-24) years). HSCT patients exhibited lower mean VO2peak (-1.42 z score, 95% confidential interval (-1.7; -1.1)) compared with healthy subjects (P<0.001). Sixteen patients (25%) had VO2peak values <-1.96 z-score. Low VO2peak was associated with reduced forced expiratory volume in 1 s (R(2)=0.11, P=0.009), reduced DLCO/VA (R(2)=0.09, P=0.01) and low physical activity (mean VO2peak z score inactive group: -2.1 vs most active group: -1.1, P=0.02). No associations between VO2peak and diagnosis, donor type or GvHD were found. Although causes for reduced VO2peak may be multiple, our findings stress the need to focus on physical activity post HSCT to prevent lifestyle diseases and improve quality of life. PMID- 25111516 TI - Risk factors for vancomycin-resistant enterococcus bacteremia and its influence on survival after allogeneic hematopoietic cell transplantation. AB - Vancomycin-resistant enterococcus (VRE) is a well-known infectious complication among immunocompromised patients. We performed a retrospective analysis to identify risk factors for the development of VRE bacteremia (VRE-B) within 15 months after allogeneic hematopoietic cell transplantation (alloHCT) and to determine its prognostic importance for other post-transplant outcomes. Eight hundred consecutive adult patients who underwent alloHCT for hematologic diseases from 1997 to 2011 were included. Seventy-six (10%) developed VRE-B at a median of 46 days post transplant. Year of transplant, higher HCT comorbidity score, a diagnosis of ALL, unrelated donor and umbilical cord blood donor were all significant risk factors on multivariable analysis for the development of VRE-B. Sixty-seven (88%) died within a median of 1.1 months after VRE-B, but only four (6%) of these deaths were attributable to VRE. VRE-B was significantly associated with worse OS (hazard ratio 4.28, 95% confidence interval 3.23-5.66, P<0.001) in multivariable analysis. We conclude that the incidence of VRE-B after alloHCT has increased over time and is highly associated with mortality, although not usually attributable to VRE infection. Rather than being the cause, this may be a marker for a complicated post-transplant course. Strategies to further enhance immune reconstitution post transplant and strict adherence to infection prevention measures are warranted. PMID- 25111518 TI - Caecal rupture associated with Ogilvie syndrome following caesarean hysterectomy due to morbidly adherent placenta. PMID- 25111519 TI - Hysteroscopic management of an oblique vaginal septum in a virgin girl with a rare variant of Herlyn-Werner-Wunderlich syndrome. AB - STUDY OBJECTIVE: To demonstrate a technique for hysteroscopic diagnosis and management of a rare variant of Herlyn-Werner-Wunderlich syndrome (HWWS) in a virgin girl. DESIGN: Presentation of a rare variant of HWWS and a step-by-step description of the technique using videos, images, and title slides (educative video) (Canadian Task Force classification III). SETTING: HWWS is a congenital anomaly of the urogenital tract, typically characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Of HWWS cases, 11.5% are a rare variant of the syndrome, with a septate bicollis uterus and obstructed hemivagina. HWWS is often diagnosed in adolescent girls and virgin patients. Early diagnosis and treatment should be achieved using a convenient, minimally invasive, and effective surgical approach to prevent complications. INTERVENTIONS: A 14-year-old virgin girl had aggressive cyclic dysmenorrhea for 7 months. We made a diagnosis of the non-classic HWWS variant: septate uterus with double cervix, obstructed right hemivagina with hematocolpos, and unilateral renal agenesis. Diagnostic hysteroscopy indicated a flat hemivaginal septum, left cervix, and uterine cavity, but no right cervix or other associated channel. Hysteroscopic incision of the bulging oblique vaginal septum was performed medially from the most prominent point of the septum up to the left cervix and then down to the low edge of the oblique septum. An inflated Foley catheter was placed in the right hemivagina for 2 days to prevent adhesion of the incised septum. Surgery was successful, and the intact hymen was preserved. The patient has been symptom-free for 4 months after surgery. CONCLUSION: Hysteroscopic incision of the oblique vaginal septum is a convenient, minimally invasive, and effective approach for treating HWWS in adolescents with cyclic dysmenorrhea and hematocolpos. PMID- 25111521 TI - The Medially Migrating Intracanalicular Vestibular Schwannoma. PMID- 25111517 TI - The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD. AB - Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic SCT (allo-HSCT). Several risk factors have been suggested including BU-containing myeloablative conditioning, unrelated donors and GVHD, but these have not been consistently reported. We conducted a retrospective study including 339 allo-HSCT recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2 year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients (84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result (mean 2.0 * 10(10) copies of DNA per mL). In univariate analysis, myeloablative conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4 were significantly associated with the risk of HC. Multivariate analysis confirmed all associating factors identified in univariate analysis except for HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63, P=0.003), CMV viremia (HR 1.88, P=0.014) and aGVHD grade 3-4 (HR 1.71, P=0.029). HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%. Three clinical factors associated with HC were identified including myeloablative conditioning, CMV viremia and severe aGVHD. PMID- 25111520 TI - Protein-engineered hydrogel encapsulation for 3-D culture of murine cochlea. AB - HYPOTHESIS: Elastin-like protein (ELP) hydrogel helps maintain the three dimensional (3-D) cochlear structure in culture. BACKGROUND: Whole-organ culture of the cochlea is a useful model system facilitating manipulation and analysis of live sensory cells and surrounding nonsensory cells. The precisely organized 3-D cochlear structure demands a culture method that preserves this delicate architecture; however, current methods have not been optimized to serve such a purpose. METHODS: A protein-engineered ELP hydrogel was used to encapsulate organ of Corti isolated from neonatal mice. Cultured cochleae were immunostained for markers of hair cells and supporting cells. Organ of Corti hair cell and supporting cell density and organ dimensions were compared between the ELP and nonencapsulated systems. These culture systems were then compared with noncultured cochlea. RESULTS: After 3 days in vitro, vital dye uptake and immunostaining for sensory and nonsensory cells show that encapsulated cochlea contain viable cells with an organized architecture. In comparison with nonencapsulated cultured cochlea, ELP-encapsulated cochleae exhibit higher densities of hair cells and supporting cells and taller and narrower organ of Corti dimensions that more closely resemble those of noncultured cochleae. However, we found compromised cell viability when the culture period extended beyond 3 days. CONCLUSION: We conclude that the ELP hydrogel can help preserve the 3-D architecture of neonatal cochlea in short-term culture, which may be applicable to in vitro study of the physiology and pathophysiology of the inner ear. PMID- 25111522 TI - Round window stimulation for conductive and mixed hearing loss. AB - OBJECTIVE: Assess surgical complications, postoperative residual hearing, and speech perception outcomes of placement of a middle ear implant on the round window in conductive and mixed hearing loss cases. STUDY DESIGN: Single-subject, repeated-measures design where each subject served as his or her own control. SETTING: Tertiary referral medical systems. SUBJECTS: Eighteen subjects with either conductive or mixed hearing loss who could not benefit from conventional amplification were enrolled in a clinical trial investigating vibratory stimulation of the round window. INTERVENTION: The floating mass transducer (FMT) was positioned in the round window niche. MAIN OUTCOME MEASURES: Unaided residual hearing, and aided sound field thresholds and speech perception abilities were evaluated preoperatively, and at 1, 3, 6, and 10 months post-activation of the external speech processor. RESULTS: Six subjects experienced complications that either required further medical management or resolved on their own. There was no difference in residual bone conduction thresholds or unaided word discrimination over time. All subjects experienced a significant improvement in aided speech perception abilities as compared to preoperative performance. CONCLUSION: Subjects with conductive and mixed hearing loss with placement of the FMT in the round window niche experienced improved sound field thresholds and speech perception, without compromising residual hearing thresholds. Vibratory stimulation of the round window via a middle ear implant may be an appropriate treatment option for patients with conductive and mixed hearing loss. Additional research is needed on the preferred placement of the FMT, improvement of functional gain, and methods to limit postoperative complications and need for revision surgery. PMID- 25111523 TI - The rising incidence of spontaneous cerebrospinal fluid leaks in the United States and the association with obesity and obstructive sleep apnea. AB - OBJECTIVE: To determine the national rates of spontaneous CSF leaks and to determine the association with risk factors. STUDY DESIGN: Retrospective review from 2002 to 2012. SETTING: University HealthSystem Consortium (UHC) database of 127 of the leading academic medical centers in the United States (81 centers participated all years of the study). PATIENTS: Those who underwent craniotomy for CSF leak repair in the UHC database and those who have undergone repair of spontaneous CSF leaks at one UHC center. INTERVENTION: Assessment of procedure code rates and patient demographics from 2002 to 2012. MAIN OUTCOME MEASURE: National rates of craniotomy for spontaneous CSF leak repair each year, the relation to U.S. regional obesity rates, and the proportion of patients with coincident obstructive sleep apnea. Spontaneous CSF leak patient characteristics (age, sex, BMI, hypertension, and OSA) were calculated. RESULTS: The rate of craniotomy for spontaneous CSF leak repair has risen 2 fold from 2002 (218 cases per year) to 2012 (488 cases per year). There was no change in the rate of nonspontaneous CSF leaks over the same period. The rate of spontaneous CSF leak repair is twice as high (2.54 versus 1.07 per million people per year) in regions of the United States with the highest obesity rate (Midwest) compared with the lowest obesity rate (West). All patients with spontaneous CSF leaks were overweight (BMI, >25 kg/m2) with an average BMI of 37.8 kg/m2. The average age was 57.03 years, and 72% were female. Patients with spontaneous CSF leaks presented with high rate of OSA (14.8% nationally and 37.1% at the University of Iowa) and hypertension (85.7%). CONCLUSION: The national rate of craniotomy for spontaneous CSF leak repair is rising. This condition is yet another public health problem related to the rising obesity epidemic. All patients with spontaneous CSF leaks should be evaluated for OSA. PMID- 25111524 TI - Intralabyrinthine schwannomas mimic cochleovestibular disease: symptoms from tumor mass effect in the labyrinth. AB - OBJECTIVE: To describe symptoms from intralabyrinthine schwannomas specific from more common vestibular schwannomas of the internal auditory canal or cerebellopontine angle resulting from mass effect from the tumor within the labyrinth. PATIENTS: Eight patients diagnosed as having intralabyrinthine schwannomas from 2000 to 2014 were examined retrospectively from two tertiary neurotologic centers. INTERVENTIONS: Diagnosis of intralabyrinthine schwannoma was made with gadolinium-enhanced magnetic resonance imaging scans. Heavily T2 weighted sequences were used to verify mass within the fluid-filled labyrinth. Patients then underwent audiometric and vestibular testing when appropriate. Treatment consisted of observation or surgical resection. MAIN OUTCOME MEASURES: Clinical symptoms, magnetic resonance imaging scans, audiometric and videonystagmography data, and operative findings were reviewed. RESULTS: Five of the eight patients had positional vertigo or nystagmus on testing. One patient's only complaint was positional vertigo without auditory symptoms. Three of the patients demonstrated mixed hearing loss. Two patients underwent resection of their tumors, one because of tumor growth and the other because of intractable vertigo. CONCLUSION: These data show that a high proportion within our series displayed symptoms of positional vertigo and mixed hearing loss, which are symptoms not typical of nonintralabyrinthine schwannomas. One patient's only reported symptom was positional vertigo. These symptoms may arise from the effect of the tumor's mass exerted on the cochlear and vestibular end organs. PMID- 25111525 TI - A lightning strike causing a cholesteatoma: a unique form of otologic blast injury. AB - OBJECTIVE: We present a case of a middle-aged male struck by lightning while walking in a parking lot. Assessment of the patient's injuries demonstrated common sequelae of an otologic blast injury. Review of this case should prepare the otolaryngologist to identify and manage otologic blast injuries regardless of their etiology. METHODS: Case study and literature review CASE REPORT: The patient presented to a level 1 trauma and burn center with a ruptured tympanic membrane, otalgia, mixed hearing loss, dizziness, and tinnitus. After 3 months of observation, the patient's tympanic membrane perforation demonstrated little spontaneous closure. Additionally, he was noted to have formation of a posttraumatic cholesteatoma in the posterior-superior mesotympanum. Over-under tympanoplasty with excision of the cholesteatoma was successful, and the ossicular chain remained intact. The patient underwent vestibular therapy for an ipsilateral uncompensated vestibular weakness. His dizziness resolved, allowing him to return to full employment. The patient's final audiogram demonstrated normal hearing thresholds sloping to a mild mixed hearing loss in the high frequencies, and the tinnitus reduced significantly in intensity but did not resolve. CONCLUSION: The patient's injury pattern clearly resulted from the damaging effects of the shock wave generated by the lightning bolt, which impacted the patient's thorax. Management of his otologic care was conducted after practices developed for otologic blast injury and resulted in his being able to return to his primary occupation. PMID- 25111526 TI - Power spectral analysis of postural sway during foam posturography in patients with peripheral vestibular dysfunction. AB - OBJECTIVE: To assess the frequency-domain characteristics of postural instability caused by peripheral vestibular dysfunction by performing a power spectral analysis of the center of pressure (COP) sway during foam posturography. METHODS: Data were obtained from 78 patients and 163 controls. Two-legged stance tasks were performed in 4 conditions: eyes open with and without foam rubber, and eyes closed with and without foam rubber. We estimated the power spectrum of the acceleration signal using the maximum entropy method. The areas under the curve (AUCs) of power spectral density of the COP were calculated across low-frequency (0.02 to 0.1 Hz, LF-AUC), middle-frequency (0.1 to 1Hz, MF-AUC), and high frequency (1 to 10 Hz, HF-AUC) ranges. We performed binomial logistic regression analyses to see whether the AUCs of selected bandwidths of COP have a stronger association with the presence of peripheral vestibular dysfunction in comparison with the velocity and area in the eyes closed/foam rubber condition. RESULTS: In both the controls and patients, the MF-AUC was significantly larger than the LF AUC or HF-AUC in the eyes closed/foam rubber condition. In this condition, the presence of peripheral vestibular dysfunction had a significantly positive relationship with MF-AUC and HF-AUC (p < 0.05) and the MF-AUC of the anterior posterior axis showed a stronger association with the presence of peripheral vestibular dysfunction than area. CONCLUSION: An increase in activity at middle frequency movements could be characteristic of peripheral vestibular dysfunction when standing on foam rubber with the eyes closed. PMID- 25111527 TI - Genomic medicine for cancer prognosis. AB - There is a heavy research emphasis on prognostic and predictive approaches based on genomic data, which has in turn challenged standard paradigms for the management of patients with malignant disease. This review will highlight the recent advances made in genomic medicine, specifically with regard to prognosis associated with thyroid cancer, cutaneous melanoma, and pancreatic adenocarcinoma. Although none of the markers reviewed have been incorporated into routine clinical practice, this review covers the most promising ones. PMID- 25111530 TI - Re: Sarcopenia as a predictor of complications and survival following radical cystectomy: A. B. Smith, A. M. Deal, H. Yu, B. Boyd, J. Matthews, E. M. Wallen, R. S. Pruthi, M. E. Woods, H. Muss and M. E. Nielsen. J Urol 2014; 191: 1714 1720. PMID- 25111531 TI - The sigma-1 receptor agonist 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) protects against newborn excitotoxic brain injury by stabilizing the mitochondrial membrane potential in vitro and inhibiting microglial activation in vivo. AB - Premature birth represents a clinical situation of risk for brain injury. The diversity of pathophysiological processes complicates efforts to find effective therapeutic strategies. Excitotoxicity is one important factor in the pathogenesis of preterm brain injury. The observation that sigma-1 receptor agonists possess neuroprotective potential, at least partly mediated by a variety of anti-excitotoxic mechanisms, has generated great interest in targeting those receptors to counteract brain injury. The objective of this study was to evaluate the effect of the highly specific sigma-1 receptor agonist, 4-phenyl-1-(4 phenylbutyl) piperidine (PPBP) to protect against excitotoxic developmental brain injury in vivo and in vitro. Primary hippocampal neurons were pre-treated with PPBP before glutamate was applied and subsequently analyzed for cell death (PI/calcein AM), mitochondrial activity (TMRM) and morphology of the neuronal network (WGA) using confocal microscopy. Using an established neonatal mouse model we also determined whether systemic injection of PPBP significantly attenuates excitotoxic brain injury. PPBP significantly reduced neuronal cell death in primary hippocampal neurons exposed to glutamate. Neurons treated with PPBP showed a less pronounced loss of mitochondrial membrane potential and fewer morphological changes after glutamate exposure. A single intraperitoneal injection of PPBP given one hour after the excitotoxic insult significantly reduced microglial cell activation and lesion size in cortical gray and white matter. The present study provides strong support for the consideration of sigma 1 receptor agonists as a candidate therapy for the reduction of neonatal excitotoxic brain lesions and might offer a novel target to counteract developmental brain injury. PMID- 25111532 TI - Progressive multiple sclerosis cerebrospinal fluid induces inflammatory demyelination, axonal loss, and astrogliosis in mice. AB - Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination and neurodegeneration throughout the CNS, which lead over time to a condition of irreversible functional decline known as progressive MS. Currently, there are no satisfactory treatments for this condition because the mechanisms that underlie disease progression are not well understood. This is partly due to the lack of a specific animal model that represents progressive MS. We investigated the effects of intracerebroventricular injections of cerebrospinal fluid (CSF) derived from untreated primary progressive (PPMS), secondary progressive (SPMS), and relapsing/remitting (RRMS) MS patients into mice. We found discrete inflammatory demyelinating lesions containing macrophages, B cell and T cell infiltrates in the brains of animals injected with CSF from patients with progressive MS. These lesions were rarely found in animals injected with RRMS-CSF and never in those treated with control-CSF. Animals that developed brain lesions also presented extensive inflammation in their spinal cord. However, discrete spinal cord lesions were rare and only seen in animals injected with PPMS-CSF. Axonal loss and astrogliosis were seen within the lesions following the initial demyelination. In addition, Th17 cell activity was enhanced in the CNS and in lymph nodes of progressive MS-CSF injected animals compared to controls. Furthermore, CSF derived from MS patients who were clinically stable following therapy had greatly diminished capacity to induce CNS lesions in mice. Finally, we provided evidence suggesting that differential expression of pro inflammatory cytokines present in the progressive MS CSF might be involved in the observed mouse pathology. Our data suggests that the agent(s) responsible for the demyelination and neurodegeneration characteristic of progressive MS is present in patient CSF and is amenable to further characterization in experimental models of the disease. PMID- 25111533 TI - Mincle signaling in the innate immune response after traumatic brain injury. AB - The innate immune response contributes to the inflammatory activity after traumatic brain injury (TBI). In the present study we identify macrophage inducible C-type lectin (mincle) as a pattern recognition receptor that contributes to innate immunity in neurons after TBI. Here we report that mincle is activated by SAP130 in cortical neurons in culture, resulting in production of the inflammatory cytokine TNF. In addition, mincle and SAP130 are elevated in the brain and cerebrospinal fluid of humans after TBI and the brain of rodents after fluid percussion brain injury. Thus, these findings suggest the involvement of mincle to the pathology of TBI. Importantly, blocking mincle with a neutralizing antibody against mincle in cortical neurons in culture treated with SAP130 resulted in inhibition of mincle signaling and decreased TNF production. Therefore, our findings identify mincle as a contributor to the inflammatory response after TBI. PMID- 25111534 TI - Graphene-supported Pt and PtPd nanorods with enhanced electrocatalytic performance for the oxygen reduction reaction. AB - The combinational modification of the morphology, alloying, and support for Pt catalysts has been optimized towards the oxygen reduction reaction. Graphene supported PtPd nanorods have lower unfilled Pt d-states than carbon-supported Pt nanoparticles (Pt/C) and their specific and mass activities after the accelerated durability test are about 6.5 and 2.7 times higher than those of Pt/C, attributed to the synergistic electronic modification effect and graphene-metal interaction. PMID- 25111536 TI - Tandem mass spectrometry in an electrostatic linear ion trap modified for surface induced dissociation. AB - A variety of ion traps are used in mass spectrometry. A key feature shared by most of them is the ability to perform tandem mass spectrometry (MS/MS). The Orbitrap is perhaps the most notable ion trap in which MS/MS has yet to be performed. An electrostatic linear ion trap (ELIT) is analogous to an orbitrap in that ions are trapped using solely electrostatic fields. However, the relatively simple ion motion within an ELIT facilitates analysis of fragment ions produced within the device. In this report, we describe an ELIT to which we have added a target for surface induced dissociation (SID). When combined with our previously described method for isolating a precursor ion trapped in an ELIT,1 this apparatus enables MS/MS to be performed. Measurement of product ion m/z is facilitated by the fact that the ELIT is isochronous over the energy range of 1850-2000 eV so that changes to ion energy during SID do not cause major m/z shifts. We demonstrate MS/MS by isolating and dissociating each compound in a four component mixture of tetraalkylphosphonium cations. We also discuss the optimization of collision energy and the length of time that the SID target is available for collision, two parameters that are important in the performance of these experiments. PMID- 25111538 TI - Comparison of Quick Track and Melker for emergent invasive airway management during chest compression: A crossover simulation trial. PMID- 25111537 TI - Effects of ethanolic dried leaf extract of Lecaniodiscus cupanioides on antioxidant enzymes and biochemical parameters in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Lecaniodiscus cupanioides is widely used in West African folk medicine for the treatment of inflammatory conditions, fevers and bacterial infections. AIM OF THE STUDY: To evaluate the potential toxic effects of the ethanolic dried leaf extract of Lecaniodiscus cupanioides (LC) on antioxidant enzymes in selected organs and biochemical parameters. MATERIALS AND METHODS: Crude ethanolic extract of Lecaniodiscus cupanioides dried leaves was prepared. A 90-day sub-chronic toxicity study was conducted using albino rats. Reconstituted Lecaniodiscus cupanioides was administered at a dosage of 400, 800 and 1600 mg/kg (high dose) with a control group receiving 10 ml/kg orally. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture after euthanization. Selected organs (liver, kidney and brain) were harvested for antioxidant and histopathological assessments. RESULTS: The extract produced significant (p<0.05) increases in the weights of liver, kidney and brain at 800 mg/kg and 1600 mg/kg compared to the control. Biochemical analysis showed significant increase in Alanine transferase (ALT) at 800 mg/kg and 1600 mg/kg. Assay for antioxidant enzymes showed a reversible decrease in the activity of Catalase (CAT), Superoxide dismutase (SOD) and Glutathione (GSH) with an increase in Malondialdehyde (MDA) at 800 mg/kg and 1600 mg/kg Lecaniodiscus cupanioides. Histopathological study showed reversible congestion in the brain, liver, and kidney at 800 mg/kg and 1600 mg/kg. CONCLUSION: Findings in this study reveal that the ethanolic dried leaf extract of Lecaniodiscus cupanioides has the potential for inhibiting in vivo antioxidant enzymes activity and causing hepatotoxicity after prolonged exposure. PMID- 25111539 TI - Electromyographic activity of the diaphragm during neostigmine or sugammadex enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers. AB - BACKGROUND: The use of neuromuscular blocking agents has been associated with severe postoperative respiratory morbidity. Complications can be attributed to inadequate reversal, and reversal agents may themselves have adverse effects. OBJECTIVE: To compare the electromyographic activity of the diaphragm (EMGdi) during recovery from neuromuscular blockade using neostigmine and sugammadex. The hypothesis was that there would be better neuromuscular coupling of the diaphragm when sugammadex was used. DESIGN: A randomised, controlled, parallel-group, single-centre, double-blinded study. SETTING: District general hospital in Belgium. PARTICIPANTS: Twelve healthy male volunteers. INTERVENTIONS: Individuals were anaesthetised with propofol and remifentanil. After rocuronium 0.6 mg kg, a transoesophageal electromyography (EMG) recorder was inserted. For reversal of neuromuscular blockade, volunteers received sugammadex 2 mg kg (n = 6) or neostigmine 70 MUg kg (n = 6). MAIN OUTCOME MEASURES: EMGdi, airway pressure and flow were continuously measured during weaning from the ventilator until tracheal extubation. Arterial blood gas samples were obtained for PaO2 and PaCO2 analysis at the first spontaneous breathing attempt and after tracheal extubation. RESULTS: During weaning, 560 breaths were retained for analysis. The median (95% CI) peak EMGdi was 1.1 (0.9 to 1.5) MUV in the neostigmine group and 1.6 (1.3 to 1.9) MUV in the sugammadex group (P < 0.001). Individuals in the neostigmine group had 125 of 228 (55%) breaths with associated EMGdi at least 1 MUV vs. 220 of 332 (66%) breaths in the sugammadex group (P = 0.008). The median (95% CI) tidal volume was 287 (256 to 335) ml after neostigmine and 359 (313 to 398) ml after sugammadex (P = 0.013). The median (95% CI) PaO2 immediately after extubation was 30.5 (22.8 to 37.1) kPa after sugammadex vs. 20.7 (12.9 to 27.5) kPa after neostigmine (P = 0.03). CONCLUSION: EMGdi, tidal volume and PaO2 following tracheal extubation were increased after sugammadex compared with neostigmine, reflecting diaphragm-driven inspiration after sugammadex administration. Sugammadex may free more diaphragmatic acetylcholine receptors than neostigmine, which has an indirect effect. TRIAL REGISTRATION: EudraCT ref: 2013-002078-30. PMID- 25111540 TI - When visibility hurts and helps: how intersections of race and gender shape Black professional men's experiences with tokenization. AB - Research shows groups who experience minority status encounter tokenization. Most studies applying token theory to minority groups at work focus on either gendered or racialized processes of tokenization. We offer a different approach by using an intersectional lens to examine how both race and gender work together to shape ways Black professional men experience tokenization when employed in predominantly White male-dominated workplaces. Based on interviews with 42 Black men employed as doctors, lawyers, bankers, or engineers, we conclude that although Black professional men encounter some of the typical negative aspects of tokenization, intersections of race and gender create other important facets that render their token experience somewhat unique and different from their White male, White female, and Black female counterparts. PMID- 25111541 TI - Same spaces, different races: what can cafeteria seating patterns tell us about intergroup relations in middle school? AB - Using 2 segregation indices--an exposure index previously used in cafeteria studies and an entropy index used for the first time, to our knowledge, in this study--we examined racial segregation in seating patterns among ethnically diverse middle school students in their school cafeteria over a 2-week period. Given the representation of groups in the cafeteria each day, results indicated the expected amount of contact between Asian and White students, but more limited contact between Asian and Latino students and between White and Latino students. Latino students, who were in the numerical majority in the sample, appeared least likely to contribute to overall segregation in the cafeteria. Implications for using the cafeteria methodology to examine intergroup relations were discussed. PMID- 25111542 TI - Transracially adoptive parents' color-blind attitudes and views toward socialization: Cross-racial friendships as a moderator. AB - This study examined the moderating role of transracially adoptive parents' cross racial friendships in the relationship between their color-blind attitudes and views toward cultural and racial socialization. Using hierarchical multiple regression analyses and the Johnson-Neyman technique, it was hypothesized that parents' color-blind attitudes would significantly account for 3 different dimensions of socialization beliefs (i.e., prejudice awareness, ethnic pride, and egalitarian socialization) and that self-reported cross-racial friendships would moderate the effects of color-blind attitudes. Results suggest that having several cross-racial friendships minimized the effects of participants' color blind attitudes on their ethnic pride and egalitarian socialization beliefs, whereas having few cross-racial friendships enhanced the effects of color-blind attitudes on both socialization variables. The importance of transracially adoptive families creating diverse and multiracial social networks is discussed. PMID- 25111543 TI - Negotiating multiple marginalizations: experiences of South Asian LGBQ individuals. AB - Drawing from minority stress (Meyer, 2003) and feminist multicultural (Brown, 1994) theories, the present study investigated the additive and interactive relations between 2 types of external minority stress (heterosexist discrimination and racist events) and 4 internal stress processes related to identifying as a South Asian American lesbian, gay, bisexual, and queer (LGBQ) person (internalized heterosexism, acculturation, enculturation, and outness as LGBQ) with psychological distress. With 142 participants, Pearson's correlations, multiple regression, and simultaneous multiple moderation analyses were conducted. Experiences of heterosexist discrimination, racist events, and internalized heterosexism were correlated positively with psychological distress and enculturation was correlated negatively. In a test of the additive model, heterosexist discrimination, racist events, and internalized heterosexism accounted for significant and unique variance in psychological distress, but outness, acculturation, and enculturation did not. To test the interactive model, the simultaneous moderating roles of the internal stress processes were examined in the links between the external minority stressors to psychological distress. Only outness as LGBQ emerged as a moderator. The link between racist events and psychological distress was exacerbated in instances of higher outness, such that respondents with high racist events and high outness reported the highest levels of psychological distress. Clinical implications of these findings are discussed and future research directions focused on the needs of South Asian American LGBQ people are suggested. PMID- 25111545 TI - Pedagogy of the Privileged: Review of Deconstructing Privilege: Teaching and Learning as Allies in the Classroom. AB - As scholarship and research in multicultural psychology evolves to a multilayered and complex discipline, increased attention to the role of larger structural forces of privilege has come to the forefront. Intersectionality of sociopolitical identities and the role those with privilege have in confronting oppression becomes a critical component of multicultural education. The edited volume, Deconstructing Privilege: Teaching and Learning as Allies in the Classroom (Case, 2013) provides concrete guidance and examples for educators seeking to enhance their approach to teaching privilege as a necessary mirror of oppression. This review highlights strengths of the book for educators in psychology and suggests recommendations for more complex discussion of the integration of privilege within the framework of structural oppression. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID- 25111544 TI - Suicidal ideation among racial/ethnic minorities: moderating effects of rumination and depressive symptoms. AB - Among emerging adults and college students, racial and ethnic minorities experience greater risk for suicidal ideation and behavior than their White counterparts. Research has identified numerous cognitive risk factors for suicidal ideation. However, they have not been well studied among racial and ethnic minorities. The present study examined the association between these factors (brooding rumination, reflective rumination, hopelessness, and depressive symptoms) and suicidal ideation among 690 Black, Latino, and biracial college students. Among all groups, hopelessness was positively associated with suicidal ideation. Brooding was negatively associated with suicidal ideation, after adjusting for reflection and hopelessness, although only at low levels of depressive symptoms. Black race/ethnicity and Latino race/ethnicity, compared with biracial race/ethnicity, each separately interacted with reflection to predict lower levels of suicidal ideation at moderate to high levels of reflection. Furthermore, Latino race/ethnicity, compared with biracial race/ethnicity, interacted with both reflection and depressive symptoms, such that reflection was negatively associated with suicidal ideation among Latino individuals reporting depressive symptoms above the 39th percentile. Biracial race/ethnicity, compared with monoracial race/ethnicity, also interacted with reflection and depressive symptoms, with reflection associated with greater amounts of suicidal ideation at depressive symptom levels above the 39th percentile. Our findings suggest reflective rumination differentially affects racial and ethnic groups and should be considered in conjunction with depressive symptoms among Latino and biracial individuals in suicide risk assessment and treatment. PMID- 25111546 TI - Perceptions and experiences in higher education: a national study of multiracial Asian American and Latino/a students in psychology. AB - Demographic trends suggest increasing numbers of multiple racial heritage students attending U.S. campuses and universities, a change reflected within psychology. However, there is little empirical investigation into the educational experiences and needs of multiracials. The current study (the second in a series of studies to use data from a national survey of psychology graduate and undergraduate students) compared 2 multiracial groups, Asian American/European American and Latino/a/European Americans, with their single-heritage counterparts on several variables of interest-academic supports and barriers, linkage between barriers faced and ethnicity, and perceived cultural diversity. Results indicated that multiracial groups reported more of a link between academic barriers experienced and their ethnicity than European American students, but less of a link than their monoracial minority peers. No differences between groups were found related to academic supports, academic barriers, and perceived cultural diversity. Study limitations, future research, and implications are discussed. PMID- 25111547 TI - Ethnicity moderates the outcomes of self-enhancement and self-improvement themes in expressive writing. AB - The current study examined whether writing content related to self-enhancing (viz., downward social comparison and situational attributions) and self improving (viz., upward social comparison and persistence) motivations were differentially related to expressive writing outcomes among 17 Asian American and 17 European American participants. Content analysis of the essays revealed no significant cultural group differences in the likelihood of engaging in self enhancing versus self-improving reflections on negative personal experiences. However, cultural group differences were apparent in the relation between self motivation processes and changes in anxiety and depressive symptoms at 3-month follow-up. Among European Americans, writing that reflected downward social comparison predicted positive outcomes, whereas persistence writing themes were related to poorer outcomes. For Asian Americans, writing about persistence was related to positive outcomes, whereas downward social comparison and situational attributions predicted poorer outcomes. Findings provide evidence suggesting culturally distinct mechanisms for the effects of expressive disclosure. (PsycINFO Database Record PMID- 25111548 TI - Cultural distance between parents' and children's creativity: A within-country approach in Taiwan. AB - The present study adopted a within-country approach to investigate the relation of cultural distance to general creativity and math creativity in Taiwan. First, we conducted a pilot study of 201 young adolescents with parents from one of the 3 largest subethnic groups in Taiwan, namely Min-nan Taiwanese, Ha-kka Taiwanese, and Outside-Province Taiwanese. The results revealed that young Taiwanese adolescents perceived the cultural distance between Min-nan Taiwanese and Outside Province Taiwanese as larger than the cultural distance between the other subethnic groups. The main study revealed that 610 young adolescents from large cultural distance families (i.e., those comprising 1 Min-nan Taiwanese parent and 1 Outside-Province Taiwanese parent) outperformed those from small cultural distance families (i.e., those comprising 2 Min-nan Taiwanese parents, and those comprising 1 Min-nan Taiwanese parent and 1 Ha-kka Taiwanese parent) on both general creativity and math creativity. This pattern remained even after controlling for family socioeconomic status, parents' education level, and adolescents' school mathematical performance. Implications and limitations are discussed. PMID- 25111549 TI - The influence of ethnic group variation on victimization and help seeking among Latino women. AB - Interpersonal violence research on Latinos has largely ignored the ethnic group variations that are included under the pan-ethnic term Latino. The current study adds to the literature by utilizing a national sample of Latino women to examine the interpersonal victimization experiences and help-seeking responses to victimization by ethnic group. The sample was drawn from the Sexual Assault Among Latinas Study (SALAS; Cuevas & Sabina, 2010) that surveyed 2,000 self-identified adult Latino women. For the purpose of this study, victimization in the United States was examined among Mexican ethnics (73.3% of sample), Cuban ethnics (14%), and other ethnics (12.8%). Mexican ethnicity was found to be significantly associated with increased odds of experiencing any, physical, sexual, threat, and stalking victimization. Findings also show that higher levels of Latino orientation and being an immigrant were associated with decreased odds of experiencing any victimization, whereas Anglo orientation, as measured by the Brief ARSMA-II (Cuellar, Arnold, & Maldonado, 1995), was associated with greater odds of experiencing any victimization. Anglo orientation was significantly associated with formal help seeking. Taken as a whole, these findings emphasize the importance of bilingual and culturally competent services and also reveal that culturally competent services includes developing an understanding of the cultural differences between Latino ethnic groups. Specifically, service providers should be aware that Latinos of Mexican ethnicity may face unique risks for victimization. PMID- 25111550 TI - Therapist effects, working alliance, and African American women substance users. AB - African American (AfA) women with substance use disorders experience low rates of treatment retention compared to other groups of substance abusers. This is problematic since substance abuse treatment is effective only to the extent clients are retained. A weak working alliance is a significant barrier to treatment retention for AfA women. Thus, identifying therapist characteristics that facilitate a strong working alliance among this population stands as a promising step toward reducing disparities in treatment retention for this group. Therapist characteristics were explored as predictors of working alliance with AfA women substance users (N = 102). Two hypotheses were tested: (1) Population Sensitive Therapist Characteristics (PSTCs: multicultural competence, egalitarianism, and empowerment) will explain a significant amount of variance in working alliance beyond that explained by general therapist characteristics (GTCs: empathy, regard, and genuineness) and (2) GTCs will partially mediate the effect of each individual PSTC on working alliance. Hierarchical multiple regression revealed that PSTCs explained 12% of the variance in working alliance after controlling for GTCs. Bootstrapping analyses demonstrated that GTCs mediated the effect of each PSTC on working alliance. Findings suggest that therapists can facilitate a stronger working alliance with AfA women substance users through demonstration of PSTCs in addition to GTCs, and that PSTCs are facilitative because they increase the likelihood the therapist is perceived as empathic, having unconditional positive regard, and genuine. Clinical and therapist training implications are discussed. PMID- 25111551 TI - Person-environment fit: everyday conflict and coparenting conflict in Mexican origin teen mother families. AB - The current study examined whether a match or mismatch between teen mothers' cultural orientation and the cultural context of the family (i.e., familial ethnic socialization) predicted mother-daughter everyday and coparenting conflict, and in turn, teen mothers' adjustment. Participants were 204 Mexican origin teen mothers (M age = 16.81 years; SD = 1.00). Consistent with a person environment fit perspective, findings indicated that a mismatch between teen mothers' cultural orientation (i.e., high mainstream cultural involvement) and the cultural context of the family (i.e., higher levels of familial ethnic socialization) predicted greater mother-daughter everyday conflict and coparenting conflict 1 year later. However, when there was a match (i.e., high levels of familial ethnic socialization for teen mothers with high Mexican orientation), familial ethnic socialization was not associated with mother daughter conflict. In addition, mother-daughter conflict was positively associated with depressive symptoms and engagement in risky behaviors 1 year later among all teen mothers. PMID- 25111553 TI - See no evil: color blindness and perceptions of subtle racial discrimination in the workplace. AB - Workplace discrimination has grown more ambiguous, with interracial interactions often perceived differently by different people. The present study adds to the literature by examining a key individual difference variable in the perception of discrimination at work, namely individual color-blind attitudes. We examined relationships between 3 dimensions of color-blind attitudes (Racial Privilege, Institutional Discrimination, and Blatant Racial Issues) and perceptions of racial microaggressions in the workplace as enacted by a White supervisor toward a Black employee (i.e., discriminatory actions ranging from subtle to overt). Findings showed that observer views on institutional discrimination fully mediated, and blatant racial issues partially mediated, the relationships between racial group membership and the perception of workplace microaggressions. Non Hispanic Whites endorsed color blindness as institutional discrimination and blatant racial issues significantly more than members of racioethnic minority groups, and higher levels of color-blind worldviews were associated with lower likelihoods of perceiving microaggressions. Views on racial privilege did not differ significantly between members of different racial groups or affect microaggression perceptions. Implications for organizations concerned about promoting more inclusive workplaces are discussed. PMID- 25111552 TI - The joint effect of bias awareness and self-reported prejudice on intergroup anxiety and intentions for intergroup contact. AB - Two correlational studies investigated the joint effect of bias awareness-a new individual difference measure that assesses Whites' awareness and concern about their propensity to be biased-and prejudice on Whites' intergroup anxiety and intended intergroup contact. Using a community sample (Study 1), we found the predicted Bias Awareness * Prejudice interaction. Prejudice was more strongly related to interracial anxiety among those high (vs. low) in bias awareness. Study 2 investigated potential behavioral consequences in an important real world context: medical students' intentions for working primarily with minority patients. Study 2 replicated the Bias Awareness * Prejudice interaction and further demonstrated that interracial anxiety mediated medical students' intentions to work with minority populations. PMID- 25111554 TI - Mild test anxiety influences neurocognitive performance among African Americans and European Americans: identifying interfering and facilitating sources. AB - The current study examined ethnic/racial differences in test-related anxiety and its relationship to neurocognitive performance in a community sample of African American (n = 40) and European American (n = 36) adults. The authors hypothesized the following: (a) Test-anxiety related to negative performance evaluation would be associated with lower neurocognitive performance, whereas anxiety unrelated to negative evaluation would be associated with higher neurocognitive performance. (b) African American participants would report higher levels of anxiety about negative performance evaluation than European Americans. (c) European Americans would report higher levels of anxiety unrelated to negative performance evaluation. The first two hypotheses were supported: Ethnic/racial differences in test-taking anxiety emerged such that African Americans reported significantly higher levels of negative performance evaluation, which was associated with lower cognitive performance. The third hypothesis was not supported: African Americans and European Americans reported similar levels of test-anxiety unrelated to negative evaluation. PMID- 25111555 TI - The Pacific Identity and Wellbeing Scale-Revised (PIWBS-R). AB - We develop and validate a revised version of the Pacific Identity and Wellbeing Scale (the PIWBS-R). This revision extends the original 5-factor PIWBS model to include a sixth subscale assessing Cultural Efficacy (CE). The definition and item content for CE was based on a synthesis of research on self-efficacy and Pacific cultural capital. Confirmatory Factor Analysis (N = 919) supported the revised 6-factor PIWBS-R model. Validation analyses using a sample subset indicated that the PIWBS-R subscales predicted distinct criterion outcomes (Ns = 452-522). CE uniquely predicted self-reported Church Attendance, travel to the Pacific Islands, confidence in speaking Pacific heritage language, and satisfaction with health. Critically, Pacific Connectedness and Belonging and Perceived Societal Wellbeing predicted a lower likelihood of having been diagnosed with diabetes. These findings highlight the potential of the PIWBS-R model for research assessing the protective function of certain aspects of Pacific identity on health-related outcomes. A copy of the PIWBS-R, scale psychometrics, and construct definitions are provided. PMID- 25111556 TI - Mechanistic study on the palladium(II)-catalyzed synthesis of 2,3-disubstituted indoles under aerobic conditions: anion effects and the development of a low catalyst-loading process. AB - As a result of detailed mechanistic and kinetic studies, we have proposed that PdX2-catalyzed oxidative coupling of o-alkynylanilines 1 with terminal alkynes 2 under aerobic conditions is initiated by aminopalladation of 1 followed by ligand exchange of the resulting sigma-indolylpalladium(II) complex with 2, reductive elimination and N-demethylation. Side reactions associated with intermediates on the way to 2,3-disubstituted indoles 3 were identified, and the roles of acetate and iodide in channeling the reaction towards the desired product were established. Based on kinetic and spectroscopic studies, the soluble iodide ligated Pd(0) species was proposed to be the resting state of the catalyst and its oxidation to active Pd(II) species was the turnover-limiting step. Catalytic conditions with low loading of Pd(OAc)2 (0.0005 to 0.001 equiv) were subsequently developed. PMID- 25111557 TI - Vibrational dynamics and solvatochromism of the label SCN in various solvents and hemoglobin by time dependent IR and 2D-IR spectroscopy. AB - We investigated the characteristics of the thiocyanate (SCN) functional group as a probe of local structural dynamics for 2D-IR spectroscopy of proteins, exploiting the dependence of vibrational frequency on the environment of the label. Steady-state and time-resolved infrared spectroscopy are performed on the model compound methylthiocyanate (MeSCN) in solvents of different polarity, and compared to data obtained on SCN as a local probe introduced as cyanylated cysteine in the protein bovine hemoglobin. The vibrational lifetime of the protein label is determined to be 37 ps, and its anharmonicity is observed to be lower than that of the model compound (which itself exhibits solvent-independent anharmonicity). The vibrational lifetime of MeSCN generally correlates with the solvent polarity, i.e. longer lifetimes in less polar solvents, with the longest lifetime being 158 ps. However, the capacity of the solvent to form hydrogen bonds complicates this simplified picture. The long lifetime of the SCN vibration is in contrast to commonly used azide labels or isotopically-labeled amide I and better suited to monitor structural rearrangements by 2D-IR spectroscopy. We present time-dependent 2D-IR data on the labeled protein which reveal an initially inhomogeneous structure around the CN oscillator. The distribution becomes homogeneous after 5 picoseconds so that spectral diffusion has effectively erased the 'memory' of the CN stretching frequency. Therefore, the 2D IR data of the label incorporated in hemoglobin demonstrate how SCN can be utilized to sense rearrangements in the local structure on a picosecond timescale. PMID- 25111558 TI - Melasma-like hyperpigmentation induced by intense pulsed light treatment in Chinese individuals. AB - BACKGROUND: Symmetric melasma-like hyperpigmentation (MLH) has been identified in several patients following intense pulsed laser (IPL) treatment sessions. These patients exhibited no typical signs of melasma prior to IPL therapy. OBJECTIVES: To investigate the incidence of MLH in Chinese patients receiving IPL treatment and to discuss potential causative factors for this condition and potential preventive measures. METHODS: 675 patients with skin types III-IV who were treated with IPL were retrospectively studied. RESULTS: MLH was noted in 20 cases (20/675, 2.96%) within 3 months following IPL treatment session. All the patients had a pigmentary disorder prior to their IPL treatment s, the most common being photoaging or the presence of freckles. The lesions seen in 14 of the 20 cases (14/20, 70%) were multiple pigmented lesions along a wide distribution of the skin with undefined borders. Six of the cases had a strong post-treatment local reaction which also may have contributed to the MLH. In 2 cases, the original skin concern became worse following the IPL therapy and may have been a reason for the formation of MLH. In 6 cases, we noted that these individuals were not regular users of sunscreen post-therapy, despite our recommendations, which also may have contributed to the formation of their MLH. CONCLUSIONS: The adverse event and formation of IPL-induced MLH seen in Chinese individuals does have a relationship to a primary pigmentary lesion(s) and trend toward melasma prior to the IPL therapy. The IPL parameters chosen should be suitable for the skin condition being treated and should follow the recommendations of the manufacturer's default settings prior to undertaking the treatments. Post-therapy skin care and the use of appropriate sun protection are also important factors in preventing MLH. PMID- 25111559 TI - Palladium-catalyzed direct C(sp(2))-H alkoxylation of 2-aryloxypyridines using 2 pyridyloxyl as the directing group. AB - An efficient and highly regioselective palladium-catalyzed ortho-C(sp(2))-H bond alkoxylation of 2-aryloxypyridines was developed using 2-pyridyloxyl as the directing group and alcohols as alkoxylation reagents. Under an air atmosphere and in the presence of PhI(OAc)2, the reaction gave the corresponding products in moderate to good yields, and a series of functional groups could be tolerated. PMID- 25111560 TI - Gold-catalyzed 1,2-acyloxy migration/intramolecular [3+2] 1,3-dipolar cycloaddtion cascade reaction: an efficient strategy for syntheses of medium sized-ring ethers and amines. AB - A highly efficient strategy for the formation of medium-sized-ring ethers and amines based on a gold-catalyzed cascade reaction, involving enynyl ester isomerization and intramolecular [3+2] cyclization, has been developed. Various multisubstituted medium-sized-ring unsaturated ethers and amines were obtained through this transformation. This method represents one of the relatively few transition metal catalyzed intramolecular cycloaddition reactions for medium sized ring synthesis. PMID- 25111561 TI - Automatic and quantitative assessment of regional muscle volume by multi-atlas segmentation using whole-body water-fat MRI. AB - PURPOSE: To develop and demonstrate a rapid whole-body magnetic resonance imaging (MRI) method for automatic quantification of total and regional skeletal muscle volume. MATERIALS AND METHODS: The method was based on a multi-atlas segmentation of intensity corrected water-fat separated image volumes. Automatic lean muscle tissue segmentations were achieved by nonrigid registration of atlas datasets with 10 different manually segmented muscle groups. Ten subjects scanned at 1.5 T and 3.0 T were used as atlases, initial validation and optimization. Further validation used 11 subjects scanned at 3.0 T. The automated and manual segmentations were compared using intraclass correlation, true positive volume fractions, and delta volumes. RESULTS: For the 1.5 T datasets, the intraclass correlation, true positive volume fractions (mean +/- standard deviation, SD), and delta volumes (mean +/- SD) were 0.99, 0.91 +/- 0.02, -0.10 +/- 0.70L (whole body), 0.99, 0.93 +/- 0.02, 0.01 +/- 0.07L (left anterior thigh), and 0.98, 0.80 +/- 0.07, -0.08 +/- 0.15L (left abdomen). The corresponding values at 3.0 T were 0.97, 0.92 +/- 0.03, -0.17 +/- 1.37L (whole body), 0.99, 0.93 +/- 0.03, 0.03 +/- 0.08L (left anterior thigh), and 0.89, 0.90 +/- 0.04, -0.03 +/- 0.42L (left abdomen). The validation datasets showed similar results. CONCLUSION: The method accurately quantified the whole-body skeletal muscle volume and the volume of separate muscle groups independent of field strength and image resolution. PMID- 25111562 TI - An arched micro-injector (ARCMI) for innocuous subretinal injection. AB - Several critical ocular diseases that can lead to blindness are due to retinal disorders. Subretinal drug delivery has been developed recently for the treatment of retinal disorders such as hemorrhage because of the specific ocular structure, namely, the blood retinal barrier (BRB). In the present study, we developed an Arched Micro-injector (ARCMI) for subretinal drug delivery with minimal retinal tissue damage. ARCMIs were fabricated using three major techniques: reverse drawing lithography, controlled air flow, and electroplating. In order to achieve minimal retinal tissue damage, ARCMIs were fabricated with specific features such as a 0.15 mm(-1) curvature, 45 degrees tip bevel, 5 mm length, inner diameter of 40 um, and an outer diameter of 100 um. These specific features were optimized via in-vitro experiments in artificial ocular hemispherical structures and subretinal injection of indocyanine green in porcine eye ex-vivo. We confirmed that the ARCMI was capable of delivering ocular drugs by subretinal injection without unusual subretinal tissue damage, including hemorrhage. PMID- 25111563 TI - Extracellular matrix components of adipose derived stromal cells promote alignment, organization, and maturation of cardiomyocytes in vitro. AB - Adipose derived stromal cells (ADSC) are relevant therapeutic agents to treat myocardial infarction (MI) in clinical trials. Soluble factors secreted by ADSC, such as growth factors and cytokines, suppress inflammation and apoptosis while promoting angiogenesis and the proliferation of cardiomyocytes (CM). Moreover, ADSC synthesize extracellular matrix (ECM) components into the intercellular space which might contribute to their therapeutic capacity. Thus, ADSC might directly modulate the post-MI microenvironment through a combination of paracrine and juxtacrine signaling. In this study, the juxtacrine role of ADSC and ADSC derived ECM on the organization and maturation of CM was investiagated. Human ADSC synthesized and deposited a heterogenous and complex mixture of ECM components such as collagen I, III, IV, fibronectin, elastin as well as the matricellular protein periostin. Cocultures of rodent CM with human ADSC or with human ADSC-derived ECM components enhanced the cardiomyocyte alignment, their intercellular connections and the maturation of their sarcomeres, while the proliferation rate of the CM was increased and their level of hypertrophy reduced. The use of human ADSC-derived ECM could serve both to augment in vitro tissue-engineered myocardial constructs and to improve myocardial remodeling after infarction. PMID- 25111564 TI - Long survival in Leigh syndrome: new cases and review of literature. AB - Leigh syndrome (MIM 25600), also known as infantile subacute necrotizing encephalomyelopathy, is a neurodegenerative disorder with characteristic bilateral symmetric lesions in basal ganglia and subcortical brain regions. It is commonly associated with systemic cytochrome c oxidase (COX) deficiency and mutations in the SURF1 gene (MIM 185620), encoding a putative assembly or maintenance factor of COX. The clinical course is dominated by neurodevelopmental regression, brain stem, and basal ganglia involvement (e.g., dystonia, apnea) with death often occurring before the age of 10 years. Herein, we present three sisters carrying a previously reported homozygous SURF1 mutation (c.868_869insT) that is predicted to result in a truncated protein with loss of function. Our patients show heterogeneous clinical findings with different distribution patterns of metabolic lesions in brain magnetic resonance imaging (MRI) as well as a Chiari malformation with hydrocephalus in one patient. However, all three siblings show an unusual long survival (12 years and>16 years). COX activity was not detectable in one patient and strongly reduced in the other two. We discuss these findings with respect to a review of the literature. A total of 15 additional patients with survival>14 years have been reported so far. Overall, no clear genotype-phenotype correlations are detectable among these patients. PMID- 25111565 TI - Researchers-in-residence: a solution to the challenge of evidence-informed improvement? PMID- 25111566 TI - Increased low-frequency oscillation amplitude of sensorimotor cortex associated with the severity of structural impairment in cervical myelopathy. AB - Decreases in metabolites and increased motor-related, but decreased sensory related activation of the sensorimotor cortex (SMC) have been observed in patients with cervical myelopathy (CM) using advanced MRI techniques. However, the nature of intrinsic neuronal activity in the SMC, and the relationship between cerebral function and structural damage of the spinal cord in patients with CM are not fully understood. The purpose of this study was to assess intrinsic neuronal activity by calculating the regional amplitude of low frequency fluctuations (ALFF) using resting-state functional MRI (rs-fMRI), and correlations with clinical and imaging indices. Nineteen patients and 19 age- and sex-matched healthy subjects underwent rs-fMRI scans. ALFF measurements were performed in the SMC, a key brain network likely to impaired or reorganized patients with CM. Compared with healthy subjects, increased amplitude of cortical low-frequency oscillations (LFO) was observed in the right precentral gyrus, right postcentral gyrus, and left supplementary motor area. Furthermore, increased z-ALFF values in the right precentral gyrus and right postcentral gyrus correlated with decreased fractional anisotropy values at the C2 level, which indicated increased intrinsic neuronal activity in the SMC corresponding to the structural impairment in the spinal cord of patients with CM. These findings suggest a complex and diverging relationship of cortical functional reorganization and distal spinal anatomical compression in patients with CM and, thus, add important information in understanding how spinal cord integrity may be a factor in the intrinsic covariance of spontaneous low-frequency fluctuations of BOLD signals involved in cortical plasticity. PMID- 25111567 TI - Preparation and multiple antitumor properties of AuNRs/spinach extract/PEGDA composite hydrogel. AB - In this study, a novel composite hydrogel that contains spinach extract (SE), gold nanorods (AuNRs), and poly(ethylene glycol) double acrylates (PEGDA) is prepared through a one-step in situ photopolymerization under noninvasive 660 nm laser irradiation for localized antitumor activity. SE plays a role as a photoinitiator for initiating the formation of the PEGDA hydrogel and as an excellent photosensitizer for generating cytotoxic singlet oxygen ((1)O2) with oxygen to kill tumor cells. AuNRs can be used as a photoabsorbing agent to generate heat from optical energy. Moreover, the introduction of AuNRs is conducive to the formation of the hydrogel and accelerates the rate of (1)O2 generation. The composite hydrogel shell, which has good biocompatibility on tumor cells, can prevent the photosensitizer from migrating to normal tissue and maintains a high concentration on lesions, thereby enhancing the curative effect. The combination of NIR light-triggered mild photothermal heating of AuNRs, the photodynamic treatment using SE, and localized gelation by photopolymerization exhibits a synergistic effect for the destruction of cancer cells. PMID- 25111568 TI - The association of genes involved in the angiogenesis-associated signaling pathway with risk of anterior cruciate ligament rupture. AB - Angiogenesis-associated signaling is a fundamental component in the remodeling of the extracellular matrix in response to loading. Genes encoding protein components within this signaling cascade are therefore suitable candidates for investigation into ACL injury susceptibility: namely, vascular endothelial growth factor A isoform (VEGFA), kinase insert-domain receptor (KDR), nerve growth factor (NGF), and hypoxia inducible factor-1alpha (HIF1A). A case-control genetic association study was conducted on 227 asymptomatic control participants and 227 participants with surgically diagnosed ACL ruptures of which 126 participants reported a non-contact mechanism of rupture. All participants were genotyped for seven polymorphisms within the four genes. The VEGFA rs699947 CC genotype (p=0.010, OR: 1.92, 95% CI: 1.17-3.17) was significantly over-represented within participants with non-contact ACL ruptures. The VEGFA rs1570360 GA genotype was significantly over-represented in the CON group (p=0.007, OR: 1.70, 95% CI: 1.16 2.50). Furthermore, the KDR rs2071559 GA genotype was significantly over represented in the female controls (p=0.023, OR: 2.16, 95% CI: 1.11-4.22). Inferred haplotype analyses also implicated genomic regions spanning the VEGFA and KDR genes. These novel findings suggest that regions within VEGFA and KDR may be implicated in the pathophysiology of ACL ruptures; highlighting the potential biological significance of angiogenesis-associated signaling in the aetiology of ACL ruptures. PMID- 25111569 TI - Venous thromboembolism after diaphragm pacing in amyotrophic lateral sclerosis. AB - INTRODUCTION: Patients with amyotrophic lateral sclerosis (ALS) are prone to venous thromboembolism (VTE) and secondary complications. Because there is an increased incidence of VTE after surgical procedures, placement of a Diaphragm Pacing System (DPS) in ALS patients as treatment for respiratory muscle weakness could potentially increase the incidence of VTE, especially in patients with limited mobility. METHODS: We implanted a DPS in 10 ALS patients who met the criteria for this procedure. They underwent a preoperative evaluation as recommended by the guidelines. RESULTS: We report 2 patients with no symptoms of deep vein thrombosis (DVT) before the surgical procedure who then developed perioperative VTE. CONCLUSIONS: These patients highlight the need to consider preoperative screening for DVT and postoperative thromboprophylaxis in high-risk ALS patients who undergo DPS placement. PMID- 25111570 TI - The combination use of platelet-rich fibrin and treated dentin matrix for tooth root regeneration by cell homing. AB - Endogenous regeneration through cell homing provides an alternative approach for tissue regeneration, except cell transplantation, especially considering clinical translation. However, tooth root regeneration through cell homing remains a provocative approach in need of intensive study. Both platelet-rich fibrin (PRF) and treated dentin matrix (TDM) are warehouses of various growth factors, which can promote cell homing. We hypothesized that endogenous stem cells are able to sense biological cues from PRF membrane and TDM, and contribute to the regeneration of tooth root, including soft and hard periodontal tissues. Therefore, the biological effects of canine PRF and TDM on periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMSCs) were evaluated respectively in vitro. Beagle dogs were used as orthotopic transplantation model. It was found that PRF significantly recruited and stimulated the proliferation of PDLSCs and BMSCs in vitro. Together, PRF and TDM induced cell differentiation by upregulating the mineralization-related gene expression of bone sialoprotein (BSP) and osteopotin (OPN) after 7 days coculture. In vivo, transplantation of autologous PRF and allogeneic TDM into fresh tooth extraction socket achieved successful root regeneration 3 months postsurgery, characterized by the regeneration of cementum and periodontal ligament (PDL)-like tissues with orientated fibers, indicative of functional restoration. The results suggest that tooth root connected to the alveolar bone by cementum-PDL complex can be regenerated through the implantation of PRF and TDM in a tooth socket microenvironment, probably by homing of BMSCs and PDLSCs. Furthermore, bioactive cues and inductive microenvironment are key factors for endogenous regeneration. This approach provides a tangible pathway toward clinical translation. PMID- 25111571 TI - Mild traumatic brain injury defined by Glasgow Coma Scale: Is it really mild? AB - INTRODUCTION: Conventionally, a Glasgow Coma Scale (GCS) score of 13-15 defines mild traumatic brain injury (mTBI). The aim of this study was to identify the factors that predict progression on repeat head computed tomography (RHCT) and neurosurgical intervention (NSI) in patients categorized as mild TBI with intracranial injury (intracranial haemorrhage and/or skull fracture). METHODS: This study performed a retrospective chart review of all patients with traumatic brain injury who presented to a level 1 trauma centre. Patients with blunt TBI, an intracranial injury and admission GCS of 13-15 without anti-platelet and anti coagulation therapy were included. The outcome measures were: progression on RHCT and need for neurosurgical intervention (craniotomy and/or craniectomy). RESULTS: A total of 1800 patients were reviewed, of which 876 patients were included. One hundred and fifteen (13.1%) patients had progression on RHCT scan. Progression on RHCT was 8-times more likely in patients with subdural haemorrhage >=10 mm, 5 times more likely with epidural haemorrhage >=10 mm and 3-times more likely with base deficit >=4. Forty-seven patients underwent a neurosurgical intervention. Patients with displaced skull fracture were 10-times more likely and patients with base deficit >4 were 21-times more likely to have a neurosurgical intervention. CONCLUSION: In patients with intracranial injury, a mild GCS score (GCS 13-15) in patients with an intracranial injury does not preclude progression on repeat head CT and the need for a neurosurgical intervention. Base deficit greater than four and displaced skull fracture are the greatest predictors for neurosurgical intervention in patients with mild TBI and an intracranial injury. PMID- 25111572 TI - Synthesizing scientific progress: outcomes from U.S. EPA's carbonaceous aerosols and source apportionment STAR grants. AB - In response to recommendations by the National Research Council in the late 1990 s and early 2000s for critical research into understanding sources and formation mechanisms of PM2.5, EPA created multiple funding opportunities through the Science to Achieve Results (STAR) program: "Measurement, Modeling, and Analysis Methods for Airborne Carbonaceous Fine Particulate Matter" (2003) and "Source Apportionment of Particulate Matter" (2004). The carbonaceous fine PM solicitation resulted in 16 different projects focusing on the measurement methods, source identification, and exploration of the chemical and physical processes important for PM2.5 carbon in the atmosphere. The source apportionment funding opportunity led to 11 projects improving tools and characterization of source-receptor relationships of PM2.5. Many funding mechanisms include a final synopsis of funded research and published manuscripts. Here, this evaluation is extended to include citations of research published as part of these solicitations. These solicitations resulted in 275 publications that included more than 850 unique authors in 37 different journals with a weighted average 2011 impact factor of 4.21. At the time of this assessment, these publications have been cited by 13,612 peer review journal articles with 31 (11%) of the manuscripts being cited over 100 times. PMID- 25111573 TI - Incidence of acute coronary syndrome in the general Medicare population, 1992 to 2009: a real-world perspective. PMID- 25111574 TI - A review of multiple hypothesis testing in otolaryngology literature. AB - OBJECTIVES/HYPOTHESIS: Multiple hypothesis testing (or multiple testing) refers to testing more than one hypothesis within a single analysis, and can inflate the type I error rate (false positives) within a study. The aim of this review was to quantify multiple testing in recent large clinical studies in the otolaryngology literature and to discuss strategies to address this potential problem. DATA SOURCES: Original clinical research articles with >100 subjects published in 2012 in the four general otolaryngology journals with the highest Journal Citation Reports 5-year impact factors. REVIEW METHODS: Articles were reviewed to determine whether the authors tested greater than five hypotheses in at least one family of inferences. For the articles meeting this criterion for multiple testing, type I error rates were calculated, and statistical correction was applied to the reported results. RESULTS: Of the 195 original clinical research articles reviewed, 72% met the criterion for multiple testing. Within these studies, there was a mean 41% chance of a type I error and, on average, 18% of significant results were likely to be false positives. After the Bonferroni correction was applied, only 57% of significant results reported within the articles remained significant. CONCLUSIONS: Multiple testing is common in recent large clinical studies in otolaryngology and deserves closer attention from researchers, reviewers, and editors. Strategies for adjusting for multiple testing are discussed. PMID- 25111575 TI - Safety evaluation of the human-identical milk monosaccharide sialic acid (N acetyl-d-neuraminic acid) in Sprague-Dawley rats. AB - N-Acetyl-d-neuraminic acid (Neu5Ac) is the predominant form of sialic acid (Sia) in humans, while other mammals express Sia as a mixture with N-glycolyl-d neuraminic acid (Neu5Gc). Neu5Ac occurs in highest levels in the brain and in breast milk, and is therefore, coined a human-specific milk monosaccharide, and is thought to play an important nutritional role in the developing infant. Synthesized human-identical milk monosaccharide (HiMM) Neu5Ac is proposed for use in infant formulas to better simulate the free saccharides present in human breast milk. As part of the safety evaluation of HiMM Neu5Ac, a subchronic dietary toxicity study preceded by an in utero phase was conducted in Sprague Dawley rats. Neu5Ac was without maternal toxicity or compound-related adverse effects on female reproduction and on the general growth and development of offspring at a maternal dietary level of up to 2%, equivalent to a dose of 1895mg/kg body weight (bw)/day. During the subchronic phase, no compound-related adverse effects were observed in first generation rats at dietary levels of up to 2% (highest level tested), corresponding to doses of 974 and 1246mg/kgbw/day in males and females, respectively. Neu5Ac also was non-genotoxic in a series of in vitro genotoxicity/mutagenicity tests. These results support the safe use of Neu5Ac both in infant formula and as a food ingredient at levels equivalent to those found naturally in human breast milk. PMID- 25111578 TI - Stromal nodules in benign prostatic hyperplasia: morphologic and immunohistochemical characteristics. AB - BACKGROUND: One hundred forty nine stromal nodules (SNs) from transurethral resection of benign prostatic hyperplasia specimens in 39 patients (57-85 years with mean of 70.9) were investigated to characterize the SNs and to outline the etiopathogenesis of solitary fibrous tumors (SFTs) and gastrointestinal stromal tumors (GISTs) of prostate by immunohistochemistry performed on tissue microarray sections. METHODS: Antibodies used included smooth muscle actin, desmin, vimentin, and S-100 protein for subtyping, vascular endothelial growth factor, insulin-like growth factor-1, fibroblast growth factor, and TGF-beta as growth factors; CD133, c-KIT, CD34, and CD44 as stem cell markers; and estrogen (ER), progesterone (PR), and androgen receptor (AR) as hormone receptors. RESULTS: SNs were classified into four subtypes: (1) immature mesenchymal (n = 7, 4.7%); (2) fibroblastic (n = 74, 49.7%); (3) fibromuscular (n = 53, 35.6%); and (4) smooth muscular (n = 15, 10.1%) types. There were linear trends of the expression of all growth factors (VEGF, IGF-1, FGF, TGF-beta), but only CD44 stem cell marker and AR hormone receptor as maturation progressed from immature mesenchymal to smooth muscular type (Ptrend < 0.05). S-100, c-KIT, and ER were not expressed in any types of SNs. CD34 was positive in 55% of the SNs (82/149). CONCLUSIONS: The data suggest that AR and growth factors are important factors for maturation of SNs, but not influenced by the administration of 5-alpha reductase inhibitor (5ARI). Although the cells comprising the SNs seem to be not associated with the origin of prostatic GISTs, there is a possibility of a tentative link of SFTs arising from SNs of the prostate. PMID- 25111576 TI - Measures of initiation and progression to increased smoking among current menthol compared to non-menthol cigarette smokers based on data from four U.S. government surveys. AB - There are no large-scale, carefully designed cohort studies that provide evidence on whether menthol cigarette use is associated with a differential risk of initiating and/or progressing to increased smoking. However, questions of whether current menthol cigarette smokers initiated smoking at a younger age or are more likely to have transitioned from non-daily to daily cigarette use compared to non menthol smokers can be addressed using cross-sectional data from U.S. government surveys. Analyses of nationally representative samples of adult and youth smokers indicate that current menthol cigarette use is not associated with an earlier age of having initiated smoking or greater likelihood of being a daily versus non daily smoker. Some surveys likewise provide information on cigarette type preference (menthol versus non-menthol) among youth at different stages or trajectories of smoking, based on number of days smoked during the past month and/or cigarettes smoked per day. Prevalence of menthol cigarette use does not appear to differ among new, less experienced youth smokers compared to established youth smokers. While there are limitations with regard to inferences that can be drawn from cross-sectional analyses, these data do not suggest any adverse effects for menthol cigarettes on measures of initiation and progression to increased smoking. PMID- 25111579 TI - Tissue alterations in urethral and vaginal walls related to multiparity in rabbits. AB - In rodents, vaginal distention after delivery or experimental manipulation affects innervations as well as the amount of striated/smooth musculature or collagen in both the urethra and vagina. These changes are associated with modifications in excretory and reproductive processes. Although successive and consecutive vaginal deliveries (multiparity) affect the contractile and functional properties of the female lower urogenital tract (LUT), its impact on LUT morphometry, including persistency, has been barely studied. The caudal urethra (CU) and cranial (V1) and caudal (V2) pelvic vaginal regions were excised from young and adult nulliparous (YN and AN, respectively) and multiparous (YM and AM, respectively) rabbits. Tissues were histologically processed and stained with Masson's trichrome. The thickness of the tissue layers and areas covered by tissue components were measured and compared using two-way ANOVA followed by Student-Newmann-Keuls tests to determine statistical differences (P <= 0.05). Compared to YN, YM, and AN tissues showed a reduction in the thickness of the epithelium, as well as in areas covered by striated musculature, collagen, and blood vessels of the LUT. In comparison with YM, only some morphometric changes were recovered in the AM group. Our study shows that multiparity and age can be associated with epithelial and muscular atrophy of urethral and vaginal walls. The morphometry of the LUT between young and adult female rabbits varies with multiparity. These findings may help to better understand the effects of multiparity on young and adult females and its correlation with the development of pelvic dysfunctions. PMID- 25111580 TI - Statistical power and optimal design in experiments in which samples of participants respond to samples of stimuli. AB - Researchers designing experiments in which a sample of participants responds to a sample of stimuli are faced with difficult questions about optimal study design. The conventional procedures of statistical power analysis fail to provide appropriate answers to these questions because they are based on statistical models in which stimuli are not assumed to be a source of random variation in the data, models that are inappropriate for experiments involving crossed random factors of participants and stimuli. In this article, we present new methods of power analysis for designs with crossed random factors, and we give detailed, practical guidance to psychology researchers planning experiments in which a sample of participants responds to a sample of stimuli. We extensively examine 5 commonly used experimental designs, describe how to estimate statistical power in each, and provide power analysis results based on a reasonable set of default parameter values. We then develop general conclusions and formulate rules of thumb concerning the optimal design of experiments in which a sample of participants responds to a sample of stimuli. We show that in crossed designs, statistical power typically does not approach unity as the number of participants goes to infinity but instead approaches a maximum attainable power value that is possibly small, depending on the stimulus sample. We also consider the statistical merits of designs involving multiple stimulus blocks. Finally, we provide a simple and flexible Web-based power application to aid researchers in planning studies with samples of stimuli. PMID- 25111581 TI - Plerixafor and abbreviated-course granulocyte colony-stimulating factor for mobilizing hematopoietic progenitor cells in light chain amyloidosis. AB - Cytokine-based mobilization in light chain (AL) amyloidosis is frequently complicated by fluid overload, weight gain, cardiac arrhythmias, and peri mobilization mortality. We analyzed hematopoietic progenitor cells (HPC) mobilization outcomes in 49 consecutive AL amyloidosis patients at our institution between 2004 and 2013 with granulocyte colony-stimulating factor (G) (10 MUg/kg/day) (n = 25) versus an institutional protocol to limit G exposure using plerixafor (P) (.24 mg/kg s.c. starting day 3 of G 10 MUg/kg) (n = 24). G+P strategy yielded higher total CD34(+) cells/kg (12.8 * 10(6) versus 6.3 * 10(6); P < .001) and CD34(+) cells/kg collected on day 1 (10.8 * 10(6) versus 4.9 * 10(6), P = .004) compared with the G cohort. More G+P patients collected >=5 * 10(6) CD34(+) HPCs/kg (22 versus 16, P = .02) and >= 10 * 10(6) CD34(+) HPCs/kg (13 versus 5, P = .01). Four patients (16%) had mobilization failure with G; none with G+P. Peri-mobilization weight gain was lower with G+P strategy (median weight gain 1 versus 7 pounds, P = .009). Numbers of apheresis sessions (median, 1 versus 1, P = .52), number of hospitalization days (median, 1.1 versus 1.6, P = .52), transfusions, use of intravenous antibiotics, and cardiac arrhythmias were similar. In conclusion, our study demonstrates that upfront use of G+P as a mobilization strategy results in superior HPC collection, no mobilization failures, and less weight gain than G alone. PMID- 25111584 TI - Expression levels of mRNA for neurosteroidogenic enzymes 17beta-HSD, 5alpha reductase, 3alpha-HSD and cytochrome P450 aromatase in the fetal wild type and SF 1 knockout mouse brain. AB - The presence of steroidogenic enzymes in the brain suggests de novo synthesis of steroid hormones in the brain. The current study was designed to determine the developmental profiles of cytochrome p450 aromatase (cyp19), 17beta hydroxysteroid dehydrogenase (17beta-HSD), 5alpha-reductase type I and 3alpha hydroxysteroid dehydrogenase (3alpha-HSD) mRNA expression levels in the fetal mouse brain and potential influence of peripheral steroids, and the steroidogenic factor 1 (SF-1) gene on their expression. Brains were collected from WT and SF-1 knockout male and female fetuses at embryonic (E) days E12, E14, E16, and E18. Quantitative PCR analyses revealed age related increases in the expression levels of 17beta-HSD and 5alpha-reductase. Differences between genotypes in the expression levels of 17beta-HSD and 5alpha-reductase were detected on E14, with reduced levels of expression in SF-1 KO males and females for 17beta-HSD and only between females for 5alpha-reductase. Expression of 3alpha-HSD mRNA did not differ significantly between sexes, age groups or genotypes with the exception of SF-1 KO males, which had an unexplained increase in mRNA for this enzyme on day E18. Expression of cyp19 was at the limit of detection and could not be analyzed effectively. There were no sex differences and, with the exception of small difference on E14 for 17beta-HSD and 5alpha-reductase, no differences between genotypes. The results suggest that gonadal steroids do not influence the production of neurosteroids in the fetal brain, nor does SF-1 play a major role in the regulation of steroidogenic enzyme expression in the brain. PMID- 25111582 TI - Nonmyeloablative allogeneic hematopoietic stem cell transplantation for GATA2 deficiency. AB - We treated 14 patients with GATA2 deficiency using a nonmyeloablative allogeneic hematopoietic stem cell transplantation regimen. Four patients received peripheral blood stem cells from matched related donors (MRD), 4 patients received peripheral blood stem cells from matched unrelated donors (URD), 4 patients received hematopoietic stem cells from umbilical cord blood donors (UCB), and 2 patients received bone marrow cells from haploidentical related donors. MRD and URD recipients received conditioning with 3 days of fludarabine and 200 cGy total body irradiation (TBI). Haploidentical related donor recipients and UCB recipients received cyclophosphamide and 2 additional days of fludarabine along with 200 cGY TBI. MRD, URD, and UCB recipients received tacrolimus and sirolimus for post-transplantation immunosuppression, whereas haploidentical recipients received high-dose cyclophosphamide followed by tacrolimus and mycophenolate mofetil. Eight patients are alive with reconstitution of the severely deficient monocyte, B cell, and natural killer cell populations and reversal of the clinical phenotype at a median follow-up of 3.5 years. Two patients (1 URD recipient and 1 UCB recipient) rejected the donor graft and 1 MRD recipient relapsed with myelodysplastic syndrome after transplantation. We are currently using a high-dose conditioning regimen with busulfan and fludarabine in patients with GATA2 deficiency to achieve more consistent engraftment and eradication of the malignant myeloid clones. PMID- 25111585 TI - Severity of influenza and noninfluenza acute respiratory illness among pregnant women, 2010-2012. AB - OBJECTIVE: The objective of the study was to identify characteristics of influenza illness contrasted with noninfluenza acute respiratory illness (ARI) in pregnant women. STUDY DESIGN: ARI among pregnant women was identified through daily surveillance during 2 influenza seasons (2010-2012). Within 8 days of illness onset, nasopharyngeal swabs were collected, and an interview was conducted for symptoms and other characteristics. A follow-up telephone interview was conducted 1-2 weeks later, and medical records were extracted. Severity of illness was evaluated by self-assessment of 12 illness symptoms, subjective ratings of overall impairment, highest reported temperature, illness duration, and medical utilization. RESULTS: Of 292 pregnant women with ARI, 100 tested positive for influenza viruses. Women with influenza illnesses reported higher symptom severity than those with noninfluenza ARI (median score, 18 vs 16 of 36; P < .05) and were more likely to report severe subjective feverishness (18% vs 5%; P < .001), myalgia (28% vs 14%; P < .005), cough (46% vs 30%; P < .01), and chills (25% vs 13%; P < .01). More influenza illnesses were associated with fever greater than 38.9 degrees C (20% vs 5%; P < .001) and higher subjective impairment (mean score, 5.9 vs 4.8; P < .001). Differences in overall symptom severity, fever, cough, chills, early health care-seeking behavior, and impairment remained significant in multivariate models after adjusting for study site, season, age, vaccination status, and number of days since illness onset. CONCLUSION: Influenza had a greater negative impact on pregnant women than noninfluenza ARIs, as indicated by symptom severity and greater likelihood of elevated temperature. These results highlight the importance of preventing and treating influenza illnesses in pregnant women. PMID- 25111583 TI - Synergistic cytotoxicity of sorafenib with busulfan and nucleoside analogs in human FMS-like tyrosine kinase 3 internal tandem duplications-positive acute myeloid leukemia cells. AB - Clofarabine (Clo), fludarabine (Flu), and busulfan (Bu) are used in pretransplantation conditioning therapy for patients with myeloid leukemia. To further improve their efficacy in FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD)-positive acute myeloid leukemia (AML), we investigated their synergism with sorafenib (Sor). Exposure of FLT3-ITD-positive MV-4-11 and MOLM 13 cells to Bu+Clo+Flu+Sor resulted in synergistic cytotoxicity; no such synergism was observed in the FLT3-wild type THP-1 and KBM3/Bu250(6) cell lines. The drug synergism in MV-4-11 cells could be attributed to activation of DNA damage response, histone 3 modifications, inhibition of prosurvival kinases, and activation of apoptosis. Further, the phosphorylation of kinases, including FLT3, MAPK kinase (MEK), and AKT, was inhibited. The FLT3-ITD substrate STAT5 and its target gene PIM 2 product decreased when cells were exposed to Sor alone, Bu+Clo+Flu, and Bu+Clo+Flu+Sor. The level of the proapoptotic protein p53 upregulated modulator of apoptosis (PUMA) increased, whereas the level of prosurvival protein MCL-1 decreased when cells were exposed to Bu+Clo+Flu+Sor. The interactions of PUMA with MCL-1 and/or BCL-2 were enhanced when cells were exposed to Bu+Clo+Flu or Bu+Clo+Flu+Sor. The changes in the level of these proteins, which are involved in mitochondrial control of apoptosis, correlate with changes in mitochondrial membrane potential. Bu+Clo+Flu+Sor decreased mitochondrial membrane potential by 60% and caused leakage of cytochrome c, second mitochondria-derived activator of caspases (SMAC)/direct IAP Binding protein with low pI (DIABLO), and AIF from the mitochondria to the cytoplasm, caspase activation, and cell death, suggesting the activation of apoptosis. Analogous, synergistic cytotoxicity in response to Bu, Clo, Flu, and Sor was observed in mononuclear cells isolated from FLT3-ITD-positive AML patients. Although our previous studies were aimed at standardizing the conditioning regimen, the new findings suggest that patients with abnormal expression of FLT3 might further benefit from individualizing treatment through the addition of Sor to Bu+Clo+Flu, thereby providing personalized pretransplantation therapy. PMID- 25111586 TI - Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth. AB - OBJECTIVE: The purpose of this study was to investigate oxidative stress as a mechanism of preterm birth in human subjects; we examined associations between urinary biomarkers of oxidative stress that were measured at multiple time points during pregnancy and preterm birth. STUDY DESIGN: This nested case-control study included 130 mothers who delivered preterm and 352 mothers who delivered term who were originally recruited as part of an ongoing prospective birth cohort at Brigham and Women's Hospital. Two biomarkers that included 8 hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine samples that were collected at up to 4 time points (median 10, 18, 26, and 35 weeks) during gestation. RESULTS: Urinary concentrations of 8-isoprostane and 8-OHdG decreased and increased, respectively, as pregnancy progressed. Average levels of 8-isoprostane across pregnancy were associated with increased odds of spontaneous preterm birth (adjusted odds ratio, 6.25; 95% confidence interval, 2.86-13.7), and associations were strongest with levels measured later in pregnancy. Average levels of 8-OHdG were protective against overall preterm birth (adjusted odds ratio, 0.19; 95% confidence interval, 0.10-0.34), and there were no apparent differences in the protective effect in cases of spontaneous preterm birth compared with cases of placental origin. Odds ratios for overall preterm birth were more protective in association with urinary 8-OHdG concentrations that were measured early in pregnancy. CONCLUSION: Maternal oxidative stress may be an important contributor to preterm birth, regardless of subtype and timing of exposure during pregnancy. The 2 biomarkers that were measured in the present study had opposite associations with preterm birth; an improved understanding of what each represents may help to identify more precisely important mechanisms in the pathway to preterm birth. PMID- 25111587 TI - Clinical experience and follow-up with large scale single-nucleotide polymorphism based noninvasive prenatal aneuploidy testing. AB - OBJECTIVE: We sought to report on laboratory and clinical experience following 6 months of clinical implementation of a single-nucleotide polymorphism-based noninvasive prenatal aneuploidy test in high- and low-risk women. STUDY DESIGN: All samples received from March through September 2013 and drawn >=9 weeks' gestation were included. Samples that passed quality control were analyzed for trisomy 21, trisomy 18, trisomy 13, and monosomy X. Results were reported as high or low risk for fetal aneuploidy for each interrogated chromosome. Relationships between fetal fraction and gestational age and maternal weight were analyzed. Follow-up on outcome was sought for a subset of high-risk cases. False-negative results were reported voluntarily by providers. Positive predictive value (PPV) was calculated from cases with an available prenatal or postnatal karyotype or clinical evaluation at birth. RESULTS: Samples were received from 31,030 patients, 30,705 met study criteria, and 28,739 passed quality-control metrics and received a report detailing aneuploidy risk. Fetal fraction correlated positively with gestational age, and negatively with maternal weight. In all, 507 patients received a high-risk result for any of the 4 tested conditions (324 trisomy 21, 82 trisomy 18, 41 trisomy 13, 61 monosomy X; including 1 double aneuploidy case). Within the 17,885 cases included in follow-up analysis, 356 were high risk, and outcome information revealed 184 (51.7%) true positives, 38 (10.7%) false positives, 19 (5.3%) with ultrasound findings suggestive of aneuploidy, 36 (10.1%) spontaneous abortions without karyotype confirmation, 22 (6.2%) terminations without karyotype confirmation, and 57 (16.0%) lost to follow up. This yielded an 82.9% PPV for all aneuploidies, and a 90.9% PPV for trisomy 21. The overall PPV for women aged >=35 years was similar to the PPV for women aged <35 years. Two patients were reported as false negatives. CONCLUSION: The data from this large-scale report on clinical application of a commercially available noninvasive prenatal test suggest that the clinical performance of this single-nucleotide polymorphism-based noninvasive prenatal test in a mixed high- and low-risk population is consistent with performance in validation studies. PMID- 25111589 TI - The structure of cyclolinopeptide A in chloroform refined by RDC measurements. AB - Three-dimensional structures of molecules traditionally assigned from nuclear Overhauser effects and vicinal coupling constants are recently complemented by measurements of residual dipolar couplings. Residual dipolar couplings measured in a stretched poly(dimethylsiloxane) gel were used to determine the structure of cyclolinopeptide A in chloroform solution at -50 degrees C. After structure refinement, conformational details of main cluster were discussed in relation to crystal and nuclear Overhauser effect derived structures. PMID- 25111590 TI - Probing the electronic properties of individual MnPc molecules coupled to topological states. AB - Hybrid organic/inorganic interfaces have been widely reported to host emergent properties that go beyond those of their single constituents. Coupling molecules to the recently discovered topological insulators, which possess linearly dispersing and spin-momentum-locked Dirac fermions, may offer a promising platform toward new functionalities. Here, we report a scanning tunneling microscopy and spectroscopy study of the prototypical interface between MnPc molecules and a Bi2Te3 surface. MnPc is found to bind stably to the substrate through its central Mn atom. The adsorption process is only accompanied by a minor charge transfer across the interface, resulting in a moderately n-doped Bi2Te3 surface. More remarkably, topological states remain completely unaffected by the presence of the molecules, as evidenced by the absence of scattering patterns around adsorption sites. Interestingly, we show that, while the HOMO and LUMO orbitals closely resemble those of MnPc in the gas phase, a new hybrid state emerges through interaction with the substrate. Our results pave the way toward hybrid organic-topological insulator heterostructures, which may unveil a broad range of exciting and unknown phenomena. PMID- 25111591 TI - Cellular immune responses against viral pathogens in shrimp. AB - Shrimp is one of the most important commercial marine species worldwide; however, viral diseases threaten the healthy development of shrimp aquaculture. In order to develop efficient control strategies against viral diseases, researchers have begun focusing increasing attention to the molecular mechanism of shrimp innate immunity. Although knowledge of shrimp humoral immunity has grown significantly in recent years, very little information is available about the cell-mediated immune responses. Several cellular processes such as phagocytosis, apoptosis, and RNA interference critical in cellular immune response play a significant role in endogenous antiviral activity in shrimp. In this review, we summarize the emerging research and highlight key mediators of cellular immune response to viral pathogens. PMID- 25111592 TI - A rapid and label-free SERS detection method for biomarkers in clinical biofluids. AB - A metal carbonyl-functionalized nanostructured substrate can be used in a rapid and simple assay for the detection of A1AT, a potential biomarker for bladder cancer, in clinical urine samples. The assay involves monitoring changes in the carbonyl stretching vibrations of the metal carbonyl via surface-enhanced Raman spectroscopy (SERS). These vibrations lie in the absorption spectral window of 1800-2200 cm(-1), which is free of any spectral interference from biomolecules. PMID- 25111588 TI - Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women. AB - OBJECTIVE: Family studies and twin studies demonstrate that lower urinary tract symptoms and pelvic organ prolapse are heritable. This review aimed to identify genetic polymorphisms tested for an association with lower urinary tract symptoms or prolapse, and to assess the strength, consistency, and risk of bias among reported associations. STUDY DESIGN: PubMed and HuGE Navigator were searched up to May 1, 2014, using a combination of genetic and phenotype key words, including "nocturia," "incontinence," "overactive bladder," "prolapse," and "enuresis." Major genetics, urology, and gynecology conference abstracts were searched from 2005 through 2013. We screened 889 abstracts, and retrieved 78 full texts. In all, 27 published and 7 unpublished studies provided data on polymorphisms in or near 32 different genes. Fixed and random effects metaanalyses were conducted using codominant models of inheritance. We assessed the credibility of pooled associations using the interim Venice criteria. RESULTS: In pooled analysis, the rs4994 polymorphism of the ADRB3 gene was associated with overactive bladder (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7-3.6; n = 419). The rs1800012 polymorphism of the COL1A1 gene was associated with prolapse (OR, 1.3; 95% CI, 1.0-1.7; n = 838) and stress urinary incontinence (OR, 2.1; 95% CI, 1.4 3.2; n = 190). Other metaanalyses, including those for polymorphisms of COL3A1,LAMC1,MMP1,MMP3, and MMP9 did not show significant effects. Many studies were at high risk of bias from genotyping error or population stratification. CONCLUSION: These metaanalyses provide moderate epidemiological credibility for associations of variation in ADRB3 with overactive bladder, and variation of COL1A1 with prolapse. Clinical testing for any of these polymorphisms cannot be recommended based on current evidence. PMID- 25111593 TI - Role of troponin in patients with chronic kidney disease and suspected acute coronary syndrome: a systematic review. AB - BACKGROUND: Patients with chronic kidney disease (CKD) have high prevalence of elevated serum troponin levels, which makes diagnosis of acute coronary syndrome (ACS) challenging. PURPOSE: To evaluate the utility of troponin in ACS diagnosis, treatment, and prognosis among patients with CKD. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through May 2014. STUDY SELECTION: Studies examining elevated versus normal troponin levels in terms of their diagnostic performance in detection of ACS, effect on ACS management strategies, and prognostic value for mortality or cardiovascular events after ACS among patients with CKD. DATA EXTRACTION: Paired reviewers selected articles for inclusion, extracted data, and graded strength of evidence (SOE). DATA SYNTHESIS: Twenty-three studies met inclusion criteria. The sensitivity of troponin T for ACS diagnosis ranged from 71% to 100%, and specificity ranged from 31% to 86% (6 studies; low SOE). The sensitivity and specificity of troponin I ranged from 43% to 94% and from 48% to 100%, respectively (8 studies; low SOE). No studies examined how troponin levels affect management strategies. Twelve studies analyzed prognostic value. Elevated levels of troponin I or troponin T were associated with higher risk for short-term death and cardiac events (low SOE). A similar trend was observed for long-term mortality with troponin I (low SOE), but less evidence was found for long-term cardiac events for troponin I and long-term outcomes for troponin T (insufficient SOE). Patients with advanced CKD tended to have worse prognoses with elevated troponin I levels than those without them (moderate SOE). LIMITATION: Studies were heterogeneous in design and in ACS definitions and adjudication methods. CONCLUSION: In patients with CKD and suspected ACS, troponin levels can aid in identifying those with a poor prognosis, but the diagnostic utility is limited by varying estimates of sensitivity and specificity. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. PMID- 25111594 TI - Circulating tumour cells in metastatic head and neck cancers. AB - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with 650,000 new cases p/a worldwide. HNSCC causes high morbidity with a 5-year survival rate of less than 60%, which has not improved due to the lack of early detection (Bozec et al. Eur Arch Otorhinolaryngol. 2013;270: 2745-9). Metastatic disease remains one of the leading causes of death in HNSCC patients. This review article provides a comprehensive overview of literature over the past 5 years on the detection of circulating tumour cells (CTCs) in HNSCC; CTC biology and future perspectives. CTCs are a hallmark of invasive cancer cells and key to metastasis. CTCs can be used as surrogate markers of overall survival and progression-free survival. CTCs are currently used as prognostic factors for breast, prostate and colorectal cancers using the CellSearch(r) system. CTCs have been detected in HNSCC, however, these numbers depend on the technique applied, time of blood collection and the clinical stage of the patient. The impact of CTCs in HNSCC is not well understood, and thus, not in routine clinical practice. Validated detection technologies that are able to capture CTCs undergoing epithelial mesenchymal transition are needed. This will aid in the capture of heterogeneous CTCs, which can be compiled as new targets for the current food and drug administration-cleared CellSearch(r) system. Recent studies on CTCs in HNSCC with the CellSearch(r) have shown variable data. Therefore, there is an immediate need for large clinical trials encompassing a suite of biomarkers capturing CTCs in HNSCC, before CTCs can be used as prognostic markers in HNSCC patient management. PMID- 25111595 TI - Expression of heat shock protein 47, transforming growth factor-beta 1, and connective tissue growth factor in liver tissue of patients with Schistosoma japonicum-induced hepatic fibrosis. AB - SUMMARY To detect the expression of pro-fibrotic molecules, such as heat shock protein 47 (Hsp47), transforming growth factor-beta 1 (TGF-beta1) and connective tissue growth factor (CTGF) in liver specimens, and analyse their correlations with the progression of schistosomal hepatic fibrosis, liver biopsy was performed in 42 chronic schistosomiasis (CS) patients, 16 chronic hepatitis B (CHB) patients and five healthy individuals (HI). Immunohistochemistry (IHC) analyses displayed that the expression of Hsp47, TGF-beta1 and CTGF was increased in CS and CHB patients compared with HI. Using real-time PCR, the mRNA levels of Hsp47, TGF-beta1 and CTGF were higher in CS patients compared with HI. In CS patients, the mRNA levels of these genes were correlated with the stage of fibrosis, and TGF-beta1 mRNA expression was associated with the grade of inflammation. Additional analyses indicated that the mRNA levels of Hsp47 and CTGF were highly correlated with liver stiffness value and spleen thickness diameter, both of which represented the severity of fibrosis. In conclusion, the three molecules are involved in the pathogenesis of hepatic fibrosis infected by Schistosoma japonicum. TGF-beta1 participates not only in the inflammatory process, but also in the fibrotic process in which Hsp47 and CTGF probably play a key role. PMID- 25111596 TI - Contaminants of emerging concern in fresh leachate from landfills in the conterminous United States. AB - To better understand the composition of contaminants of emerging concern (CECs) in landfill leachate, fresh leachate from 19 landfills was sampled across the United States during 2011. The sampled network included 12 municipal and 7 private landfills with varying landfill waste compositions, geographic and climatic settings, ages of waste, waste loads, and leachate production. A total of 129 out of 202 CECs were detected during this study, including 62 prescription pharmaceuticals, 23 industrial chemicals, 18 nonprescription pharmaceuticals, 16 household chemicals, 6 steroid hormones, and 4 plant/animal sterols. CECs were detected in every leachate sample, with the total number of detected CECs in samples ranging from 6 to 82 (median = 31). Bisphenol A (BPA), cotinine, and N,N diethyltoluamide (DEET) were the most frequently detected CECs, being found in 95% of the leachate samples, followed by lidocaine (89%) and camphor (84%). Other frequently detected CECs included benzophenone, naphthalene, and amphetamine, each detected in 79% of the leachate samples. CEC concentrations spanned six orders of magnitude, ranging from ng L(-1) to mg L(-1). Industrial and household chemicals were measured in the greatest concentrations, composing more than 82% of the total measured CEC concentrations. Maximum concentrations for three household and industrial chemicals, para-cresol (7 020 000 ng L(-1)), BPA (6 380 000 ng L(-1)), and phenol (1 550 000 ng L(-1)), were the largest measured, with these CECs composing 70% of the total measured CEC concentrations. Nonprescription pharmaceuticals represented 12%, plant/animal sterols 4%, prescription pharmaceuticals 1%, and steroid hormones <1% of the total measured CEC concentrations. Leachate from landfills in areas receiving greater amounts of precipitation had greater frequencies of CEC detections and concentrations in leachate than landfills receiving less precipitation. PMID- 25111597 TI - Polycystic kidney disease with steatocystoma multiplex: evidences for a disruptive effect of mutated polycystin-1 on keratin 17 polymerisation. PMID- 25111598 TI - Exploring three PIPs and three TIPs of grapevine for transport of water and atypical substrates through heterologous expression in aqy-null yeast. AB - Aquaporins are membrane channels that facilitate the transport of water and other small molecules across the cellular membranes. We examined the role of six aquaporins of Vitis vinifera (cv. Touriga nacional) in the transport of water and atypical substrates (other than water) in an aqy-null strain of Saccharomyces cerevisiae. Their functional characterization for water transport was performed by stopped-flow fluorescence spectroscopy. The evaluation of permeability coefficients (Pf) and activation energies (Ea) revealed that three aquaporins (VvTnPIP2;1, VvTnTIP1;1 and VvTnTIP2;2) are functional for water transport, while the other three (VvTnPIP1;4, VvTnPIP2;3 and VvTnTIP4;1) are non-functional. TIPs (VvTnTIP1;1 and VvTnTIP2;2) exhibited higher water permeability than VvTnPIP2;1. All functional aquaporins were found to be sensitive to HgCl2, since their water conductivity was reduced (24-38%) by the addition of 0.5 mM HgCl2. Expression of Vitis aquaporins caused different sensitive phenotypes to yeast strains when grown under hyperosmotic stress generated by KCl or sorbitol. Our results also indicate that Vitis aquaporins are putative transporters of other small molecules of physiological importance. Their sequence analyses revealed the presence of signature sequences for transport of ammonia, boron, CO2, H2O2 and urea. The phenotypic growth variations of yeast cells showed that heterologous expression of Vitis aquaporins increased susceptibility to externally applied boron and H2O2, suggesting the contribution of Vitis aquaporins in the transport of these species. PMID- 25111599 TI - Atomic force microscopy reveals a morphological differentiation of chromobacterium violaceum cells associated with biofilm development and directed by N-hexanoyl-L-homoserine lactone. AB - Chromobacterium violaceum abounds in soil and water ecosystems in tropical and subtropical regions and occasionally causes severe and often fatal human and animal infections. The quorum sensing (QS) system and biofilm formation are essential for C. violaceum's adaptability and pathogenicity, however, their interrelation is still unknown. C. violaceum's cell and biofilm morphology were examined by atomic force microscopy (AFM) in comparison with growth rates, QS dependent violacein biosynthesis and biofilm biomass quantification. To evaluate QS regulation of these processes, the wild-type strain C. violaceum ATCC 31532 and its mini-Tn5 mutant C. violaceum NCTC 13274, cultivated with and without the QS autoinducer N-hexanoyl-L-homoserine lactone (C6-HSL), were used. We report for the first time the unusual morphological differentiation of C. violaceum cells, associated with biofilm development and directed by the QS autoinducer. AFM revealed numerous invaginations of the external cytoplasmic membrane of wild-type cells, which were repressed in the mutant strain and restored by exogenous C6 HSL. With increasing bacterial growth, polymer matrix extrusions formed in place of invaginations, whereas mutant cells were covered with a diffusely distributed extracellular substance. Thus, quorum sensing in C. violaceum involves a morphological differentiation that organises biofilm formation and leads to a highly differentiated matrix structure. PMID- 25111600 TI - Mating behavior of Daphnia: impacts of predation risk, food quantity, and reproductive phase of females. AB - High predation risk and food depletion lead to sexual reproduction in cyclically parthenogenetic Daphnia. Mating, the core of sexual reproduction, also occurs under these conditions. Assessment of the environmental conditions and alteration of mating efforts may aid in determining the success of sexual reproduction. Here, we evaluated the impacts of predation risk, food quantity, and reproductive phase of females on the mating behavior of Daphnia obtusa males including contact frequency and duration using video analysis. Mating-related behavior involved male-female contact (mating) as well as male-male contact (fighting). Mating frequency increased while unnecessary fighting decreased in the presence of predation risk. In addition, low food concentration reduced fighting between males. Males attempted to attach to sexual females more than asexual females, and fighting occurred more frequently in the presence of sexual females. Duration of mating was relatively long; however, males separated shortly after contact in terms of fighting behavior. Thus, assessment of environmental factors and primary sexing of mates were performed before actual contact, possibly mechanically, and precise sex discrimination was conducted after contact. These results suggest that mating in Daphnia is not a random process but rather a balance between predation risk and energetic cost that results in changes in mating and fighting strategies. PMID- 25111601 TI - Pentameric thiophene-based ligands that spectrally discriminate amyloid-beta and tau aggregates display distinct solvatochromism and viscosity-induced spectral shifts. AB - A wide range of neurodegenerative diseases are characterized by the deposition of multiple protein aggregates. Ligands for molecular characterization and discrimination of these pathological hallmarks are thus important for understanding their potential role in pathogenesis as well as for clinical diagnosis of the disease. In this regard, luminescent conjugated oligothiophenes (LCOs) have proven useful for spectral discrimination of amyloid-beta (Abeta) and tau neurofibrillary tangles (NFTs), two of the pathological hallmarks associated with Alzheimer's disease. Herein, the solvatochromism of a library of anionic pentameric thiophene-based ligands, as well as their ability to spectrally discriminate Abeta and tau aggregates, were investigated. Overall, the results from this study identified distinct solvatochromic and viscosity-dependent behavior of thiophene-based ligands that can be applied as indices to direct the chemical design of improved LCOs for spectral separation of Abeta and tau aggregates in brain tissue sections. The results also suggest that the observed spectral transitions of the ligands are due to their ability to conform by induced fit to specific microenvironments within the binding interface of each particular protein aggregate. We foresee that these findings might aid in the chemical design of thiophene-based ligands that are increasingly selective for distinct disease-associated protein aggregates. PMID- 25111604 TI - Diagnosis, mechanisms and treatment of complex regional pain syndrome. AB - PURPOSE OF REVIEW: The incidence and disease course of complex regional pain syndrome (CRPS) has been unclear until recently. This was due to inconsistent diagnostic criteria used in previous studies and a lack of large-scale prospective datasets. Multiple mechanisms of CRPS have been suggested, and recent research has begun to explain how inflammation, the immune system and the autonomic nervous system may interact with aberrant central neuroplasticity to produce the clinical picture. This review summarizes progress in these fields. RECENT FINDINGS: National registries of patients with CRPS have provided us with an invaluable insight into the epidemiology of the disorder. We now have a better understanding of the disease course and expected outcome. Widespread sensory abnormalities, not limited to the CRPS limb, have been found suggesting that systemic changes may occur. Parietal lobe dysfunction and problems with sensory motor integration have also been revealed. Abnormalities in the immune system in CRPS have also been demonstrated. SUMMARY: Recent findings in diverse research fields suggest novel treatment options for CRPS: from targeting autoimmunity to correcting abnormal body image. Many of the advances in our understanding of CRPS have arisen from the development of collaborative research efforts, such as the TREND group in the Netherlands. PMID- 25111602 TI - Abnormal mitochondrial L-arginine transport contributes to the pathogenesis of heart failure and rexoygenation injury. AB - BACKGROUND: Impaired mitochondrial function is fundamental feature of heart failure (HF) and myocardial ischemia. In addition to the effects of heightened oxidative stress, altered nitric oxide (NO) metabolism, generated by a mitochondrial NO synthase, has also been proposed to impact upon mitochondrial function. However, the mechanism responsible for arginine transport into mitochondria and the effect of HF on such a process is unknown. We therefore aimed to characterize mitochondrial L-arginine transport and to investigate the hypothesis that impaired mitochondrial L-arginine transport plays a key role in the pathogenesis of heart failure and myocardial injury. METHODS AND RESULTS: In mitochondria isolated from failing hearts (sheep rapid pacing model and mouse Mst1 transgenic model) we demonstrated a marked reduction in L-arginine uptake (p<0.05 and p<0.01 respectively) and expression of the principal L-arginine transporter, CAT-1 (p<0.001, p<0.01) compared to controls. This was accompanied by significantly lower NO production and higher 3-nitrotyrosine levels (both p<0.05). The role of mitochondrial L-arginine transport in modulating cardiac stress responses was examined in cardiomyocytes with mitochondrial specific overexpression of CAT-1 (mtCAT1) exposed to hypoxia-reoxygenation stress. mtCAT1 cardiomyocytes had significantly improved mitochondrial membrane potential, respiration and ATP turnover together with significantly decreased reactive oxygen species production and cell death following mitochondrial stress. CONCLUSION: These data provide new insights into the role of L-arginine transport in mitochondrial biology and cardiovascular disease. Augmentation of mitochondrial L-arginine availability may be a novel therapeutic strategy for myocardial disorders involving mitochondrial stress such as heart failure and reperfusion injury. PMID- 25111605 TI - Regional analgesia techniques for total knee replacement. AB - PURPOSE OF REVIEW: Pain following total knee arthroplasty is a challenging task for healthcare providers. Concurrently, fast recovery and early ambulation are required to regain function and to prevent postoperative complications. Ideal postoperative analgesia provides sufficient pain relief with minimal opioid consumption and preservation of motor strength. Regional analgesia techniques are broadly used to answer these expectations. Femoral nerve blocks are performed frequently but have suggested disadvantages, such as motor weakness. The use of lumbar epidurals is questioned because of the risk of epidural hematoma. Relatively new techniques, such as local infiltration analgesia or adductor canal blocks, are increasingly discussed. The present review discusses new findings and weight between known benefits and risks of all of these techniques for total knee arthroplasty. RECENT FINDINGS: Femoral nerve blocks are the gold standard for total knee arthroplasty. The standard use of additional sciatic nerve blocks remains controversial. Lumbar epidurals possess an unfavourable risk/benefit ratio because of increased rate of epidural hematoma in orthopaedic patients and should be reserved for lower limb amputation; peripheral regional techniques provide comparable pain control, greater satisfaction and less risk than epidural analgesia. Although motor weakness might be greater with femoral nerve blocks compared with no regional analgesia, new data point towards a similar risk of falls after total knee arthroplasty with or without peripheral nerve blocks. Local infiltration analgesia and adductor canal blockade are promising recent techniques to gain adequate pain control with a minimum of undesired side effects. SUMMARY: Femoral nerve blocks are still the gold standard for an effective analgesia approach in knee arthroplasty and should be supplemented (if needed) by oral opioids. An additional sciatic nerve blockade is still controversial and should be an individual decision. Large-scale studies are needed to reinforce the promising results of newer regional techniques, such as local infiltration analgesia and adductor canal block. PMID- 25111603 TI - DNA methylation modifications associated with chronic fatigue syndrome. AB - Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Gene ontology (GO) and network analysis of differentially methylated genes was performed to determine potential biological pathways showing changes in DNA methylation in CFS. We found an increased abundance of differentially methylated genes related to the immune response, cellular metabolism, and kinase activity. Genes associated with immune cell regulation, the largest coordinated enrichment of differentially methylated pathways, showed hypomethylation within promoters and other gene regulatory elements in CFS. These data are consistent with evidence of multisystem dysregulation in CFS and implicate the involvement of DNA modifications in CFS pathology. PMID- 25111606 TI - Colorectal cancers mimic structural organization of normal colonic crypts. AB - Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear beta-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes. PMID- 25111607 TI - Preterm birth related to post-endoscopic retrograde cholangiopancreatography pancreatitis in pregnancy with newly diagnosed primary sclerosing cholangitis. PMID- 25111609 TI - Outline-based morphometrics, an overlooked method in arthropod studies? AB - Modern methods allow a geometric representation of forms, separating size and shape. In entomology, as well as in many other fields involving arthropod studies, shape variation has proved useful for species identification and population characterization. In medical entomology, it has been applied to very specific questions such as population structure, reinfestation of insecticide treated areas and cryptic species recognition. For shape comparisons, great importance is given to the quality of landmarks in terms of comparability. Two conceptually and statistically separate approaches are: (i) landmark-based morphometrics, based on the relative position of a few anatomical "true" or "traditional" landmarks, and (ii) outline-based morphometrics, which captures the contour of forms through a sequence of close "pseudo-landmarks". Most of the studies on insects of medical, veterinary or economic importance make use of the landmark approach. The present survey makes a case for the outline method, here based on elliptic Fourier analysis. The collection of pseudo-landmarks may require the manual digitization of many points and, for this reason, might appear less attractive. It, however, has the ability to compare homologous organs or structures having no landmarks at all. This strength offers the possibility to study a wider range of anatomical structures and thus, a larger range of arthropods. We present a few examples highlighting its interest for separating close or cryptic species, or characterizing conspecific geographic populations, in a series of different vector organisms. In this simple application, i.e. the recognition of close or cryptic forms, the outline approach provided similar scores as those obtained by the landmark-based approach. PMID- 25111608 TI - Renal response to L-arginine in diabetic rats. A possible link between nitric oxide system and aquaporin-2. AB - The aim of this study was to evaluate whether L-Arginine (L-Arg) supplementation modifies nitric oxide (NO) system and consequently aquaporin-2 (AQP2) expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L Arginine. Nitric oxide synthase (NOS) activity was estimated by [14C] L citrulline production in homogenates of the renal outer medulla and by NADPH diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression. PMID- 25111610 TI - Dominant modern sublineages and a new modern sublineage of Mycobacterium tuberculosis Beijing family clinical isolates in Heilongjiang Province, China. AB - Mycobacterium tuberculosis Beijing family includes a variety of sublineages. Knowledge of the distribution of a certain sublineage of the Beijing family may help to understand the mechanisms of its rapid spread and to establish an association between a certain genotype and the disease outcome. We have previously found that M. tuberculosis Beijing family clinical isolates represent approximately 90% of the clinical isolates from Heilongjiang Province, China. To clarify the distribution of M. tuberculosis Beijing family sublineages in Heilongjiang Province, China and to investigate the regularity rule for their evolution, we examined single nucleotide polymorphisms (SNPs) of 250 M. tuberculosis Beijing family clinical isolates using 10 SNP loci that have been identified as appropriate for defining Beijing sublineages. After determining the sequence type (ST) of each isolate, the sublineages of all M. tuberculosis Beijing family isolates were determined, and phylogenetic analysis was performed. We found that 9 out of the 10 SNP loci displayed polymorphisms, but locus 1548149 did not. In total, 92.8% of the isolates in Heilongjiang Province are modern sublineages. ST10 is the most prevalent sublineage (ST10 and ST22 accounted for 63.2% and 23.6% of all the Beijing family isolates, respectively). A new ST, accounting for 4% of the Beijing family isolates in this area, was found for the first time. Each new ST isolate showed a unique VNTR pattern, and none were clustered. The present findings suggest that controlling the spread of these modern sublineages is important in Heilongjiang Province and in China. PMID- 25111611 TI - Whole genomic analysis of human G12P[6] and G12P[8] rotavirus strains that have emerged in Kenya: identification of porcine-like NSP4 genes. AB - G12 rotaviruses are globally emerging rotavirus strains causing severe childhood diarrhea. However, the whole genomes of only a few G12 strains have been fully sequenced and analyzed, of which only one G12P[4] and one G12P[6] are from Africa. In this study, we sequenced and characterized the complete genomes of three G12 strains (RVA/Human-tc/KEN/KDH633/2010/G12P[6], RVA/Human tc/KEN/KDH651/2010/G12P[8], and RVA/Human-tc/KEN/KDH684/2010/G12P[6]) identified in three stool specimens from children with acute diarrhea in Kenya, Africa. On whole genomic analysis, all three Kenyan G12 strains were found to have a Wa-like genetic backbone: G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1 (strains KDH633 and KDH684) and G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 (strain KDH651). Phylogenetic analysis showed that most genes of the three strains examined in this study were genetically related to globally circulating human G1, G9, and G12 strains. Of note is that the NSP4 genes of strains KDH633 and KDH684 appeared to be of porcine origin, suggesting the occurrence of reassortment between human and porcine strains. Furthermore, strains KDH633 and KDH684 were very closely related to each other in all the 11 gene segments, indicating derivation of the two strains from a common origin. On the other hand, strain KDH651 consistently formed distinct clusters of 10 of the 11 gene segments (VP1-2, VP4, VP6-7, and NSP1-5), indicating a distinct origin of strain KDH651 from that of strains KDH633 and KDH684. To our knowledge, this is the first report on whole genome based characterization of G12 strains that have emerged in Kenya. Our observations will provide important insights into the evolutionary dynamics of emerging G12 rotaviruses in Africa. PMID- 25111613 TI - Spread and predominance in Japan of novel G1P[8] double-reassortant rotavirus strains possessing a DS-1-like genotype constellation typical of G2P[4] strains. AB - Rotavirus is a major cause of severe gastroenteritis in children <5 years of age worldwide, and two, live attenuated rotavirus vaccines are globally available. As rotavirus vaccines are introduced into national immunization programs, there is an increasing need to monitor circulating wild-type strains. However, few studies have systematically examined their full genotype constellation. This study was therefore undertaken to characterize the whole genotype constellation of circulating rotavirus strains in three widely-separated locations in Japan during the 2012 rotavirus season when rotavirus vaccines became available in the country for the first time. Of 107 rotavirus-positive specimens, 50 (46.7%) strains collected from all three locations possessed an unusual G1-P[8]-I2-R2-C2-M2-A2-N2 T2-E2-H2 constellation in which a typical G2P[4] strain appeared to have acquired its two surface protein genes from the most common G1P[8] strain. These G1P[8] double-reassortant strains were shown to possess the 11 genome segments virtually indistinguishable from each other in their nucleotide sequences and phylogenetic lineages except for two strains that underwent further intra-genotype reassortment. Successful spread to and predominance in broad locations across Japan of novel rotavirus strains possessing a genotype constellation that was previously thought not to be preferred suggests unexpected genomic flexibility of the genotype constellation. PMID- 25111612 TI - Preponderant clonal evolution of Trypanosoma cruzi I from Argentinean Chaco revealed by Multilocus Sequence Typing (MLST). AB - Trypanosoma cruzi has been historically classified as a species with preponderant clonal evolution (PCE). However, with the advent of highly polymorphic markers and studies at geographically reduced scales, the PCE in T. cruzi was challenged. In fact, some studies have suggested that recombination in T. cruzi lineage I (TcI) is much more frequent than previously believed. Further analyses of TcI populations from different geographical regions of Latin America are needed to examine this hypothesis. In the present study, we contribute to this topic by analyzing the population structure of TcI from a restricted geographical area in the Chaco region, Argentina. We analyzed TcI isolates from different hosts and vectors using a Multilocus Sequence Typing (MLST) approach. These isolates were previously characterized by sequencing the spliced leader intergenic region (SL IR). Low levels of incongruence and well-supported clusters for MLST dataset were obtained from the analyses. Moreover, high linkage disequilibrium was found and five repeated and overrepresented genotypes were detected. In addition, a good correspondence between SL-IR and MLST was observed which is expected under PCE. However, recombination is not ruled out because five out of 28 pairs of loci were incompatible with strict clonality and one possible genetic exchange event was detected. Overall, our results represent evidence of PCE in TcI from the study area. Finally, considering our findings we discuss the scenario for the genetic structure of TcI. PMID- 25111614 TI - Time and temperature effects on the digestive ripening of gold nanoparticles: is there a crossover from digestive ripening to Ostwald ripening? AB - The effects of time and temperature on the gold nanoparticle sizes obtained by digestive ripening have been investigated. In digestive ripening, a polydisperse colloid, upon refluxing with a surface-active ligand in a solvent, gets converted to a nearly monodisperse one. In this study, a polydisperse gold nanoparticle system was heated in 4-tert-butyltoluene with hexadecanethiol at different temperatures, viz., 60, 90, 120, 150, and 180 degrees C for different time periods, and the trends in particle size variations were recorded. At lower temperatures such as 60 and 90 degrees C, after the initial narrowing of the size distribution, the particle sizes remain constant even though the refluxing step is continued for 24 h, substantiating the prevalence of the digestive ripening process. However, at elevated temperatures (120, 150, and 180 degrees C) particle sizes grow continuously, indicating a deviation from the digestive ripening behavior to an Ostwald ripening-type phenomenon. PMID- 25111615 TI - The effect of surgical margins on outcomes for low grade MPNSTs and atypical neurofibroma. AB - BACKGROUND AND OBJECTIVES: While convention defines atypical neurofibroma as benign and low-grade malignant peripheral nerve sheath tumors (MPNSTs) as malignant, sparse outcomes data exist for these tumors. This study reviews clinical outcomes of surgically resected low-grade MPNST and atypical neurofibroma, focusing on the effect of surgical margins on outcome. METHODS: This study is a retrospective review of 23 patients who underwent surgical resection of a low-grade MPNST or atypical neurofibroma. Treatment characteristics of adjuvant therapy and surgical margin were noted. Endpoints of local recurrence, presence of metastatic disease, disease-specific survival, and overall survival were reviewed. RESULTS: Eighteen of 23 patients (78%) had microscopically positive margins on the resection. Disease-specific survival was 100% for both atypical neurofibroma patients and those with low-grade MPNST, regardless of surgical margin. Local recurrence in terms of recurrence of measureable disease occurred in 2/12 (16.7%) of LGMPNST patients and 1/11 (9.1%) of atypical NF patients, all of whom had microscopically positive surgical margins. CONCLUSIONS: In a study dedicated exclusively to "intermediate" nerve sheath tumors, no patients developed metastatic disease nor died of disease despite a high rate of microscopically positive surgical margins (78%). While positive margins did lead to increased rates of local recurrence, these data suggest that surgeons potentially can temper their zeal for negative surgical margins in the setting of low-grade MPNST and atypical neurofibroma, as surgical morbidity may be more important than a presumed survival benefit of wide resection. PMID- 25111616 TI - SERPINB3/B4 contributes to early inflammation and barrier dysfunction in an experimental murine model of atopic dermatitis. AB - Serine proteases are critical for epidermal barrier homeostasis, and their aberrant expression and/or activity is associated with chronic skin diseases. Elevated levels of the serine protease inhibitors SERPINB3 and SERPINB4 are seen in patients with atopic dermatitis and psoriasis. However, their mechanistic role in the skin is unknown. To evaluate the contribution of Serpinb3a (mouse homolog of SERPINB3 and SERPINB4) in atopic dermatitis, we examined the effect of topical Aspergillus fumigatus extract exposure in wild-type and Serpinb3a-null mice on transepidermal water loss (TEWL), sensitization, and inflammation. Allergen exposure induced Serpinb3a expression in the skin, along with increased TEWL, epidermal thickness, and skin inflammation, all of which were attenuated in the absence of Serpinb3a. Attenuated TEWL correlated with decreased expression of the pro-inflammatory marker S100A8. Silencing of SERPINB3/B4 in human keratinocytes decreased S100A8 expression, supporting a role for SERPINB3/B4 in the initiation of the acute inflammatory response. RNA-seq analysis following allergen exposure identified a network of pro-inflammatory genes induced in wild-type mice that was absent in Serpinb3a-null mice. In conclusion, Serpinb3a deficiency attenuates barrier dysfunction and the early inflammatory response following cutaneous allergen exposure, supporting a role for Serpinb3a (mice) and SERPINB3/B4 (humans) early in atopic dermatitis. PMID- 25111618 TI - Long-term IFN-gamma and IL-2 response for detection of latent tuberculosis infection in healthcare workers with discordant immunologic results. AB - Discordant results between the interferon-gamma release assays (IGRAs) and tuberculin skin test (TST) are common in latent tuberculosis infection (LTBI). We evaluated whether the measurement of IFN-gamma and interleukin (IL)-2T-cell responses, after prolonged Mycobacterium tuberculosis-specific antigen stimulation, can be used as adjunctive biomarker for LTBI detection in subjects with discordant results between TST and QuantiFERON-Gold In-Tube (QFT). 196 healthcare workers were screened for LTBI and in 90 of those participants, the QFT was repeated after 18 h, and IFN-gamma/IL-2 immune response was measured after 72 h long-term stimulation. Of the 196 patients, 34 had positive, 155 negative, and 7 indeterminate QFT results. Discordant TST+/QFT- results were found in 29 (14.7%) patients, of whom 6 (20.6%) were Bacillus Calmette-Guerin (BCG) vaccinated. None of 23 non-BCG vaccinated subjects showed a specific IFN gamma immune response after 18 h nor 72 h of incubation, whereas 3/23 (13.04%) discordant subjects produced a specific long-term IL-2 response, which might reflect a LTBI status. In LTBI group (TST+/QFT+) both cytokine levels were increased after long-term in comparison to short-term stimulation. No significant long-term IFN-gamma/IL-2 secretion was detected in control group (TST-/QFT-). Taken together, our data showed that the 87% of discordant patients who did not respond to the long-term assay, as controls subjects, were judged LTBI negative. The use of classic QFT and long-term IL-2 response may have a potential role to clarify the LTBI status in individuals in whom the diagnosis of LTBI is uncertain due to the discordance of the available diagnostic tests, such as TST and IGRA. PMID- 25111617 TI - Comparison of molecular signatures from multiple skin diseases identifies mechanisms of immunopathogenesis. AB - The ability to obtain gene expression profiles from human disease specimens provides an opportunity to identify relevant gene pathways, but is limited by the absence of data sets spanning a broad range of conditions. Here, we analyzed publicly available microarray data from 16 diverse skin conditions in order to gain insight into disease pathogenesis. Unsupervised hierarchical clustering separated samples by disease as well as common cellular and molecular pathways. Disease-specific signatures were leveraged to build a multi-disease classifier, which predicted the diagnosis of publicly and prospectively collected expression profiles with 93% accuracy. In one sample, the molecular classifier differed from the initial clinical diagnosis and correctly predicted the eventual diagnosis as the clinical presentation evolved. Finally, integration of IFN-regulated gene programs with the skin database revealed a significant inverse correlation between IFN-beta and IFN-gamma programs across all conditions. Our study provides an integrative approach to the study of gene signatures from multiple skin conditions, elucidating mechanisms of disease pathogenesis. In addition, these studies provide a framework for developing tools for personalized medicine toward the precise prediction, prevention, and treatment of disease on an individual level. PMID- 25111619 TI - Pattern of Uveitis in a Referral Ophthalmology Center in the Central District of Thailand. AB - PURPOSE: To report the pattern of uveitis in a major ophthalmology center in the central district of Thailand. METHODS: A retrospective study was performed in uveitis cases visiting the Department of Ophthalmology at Rajavithi Hospital, Thailand, from January 2007 to October 2012. RESULTS: Four hundred and forty-six patients (mean age 42 years, female 53.8%) were included in the study. Uveitis was unilateral in 51.1% of cases. Anterior uveitis was the most common (44.8%) case, closely followed by panuveitis (40%), posterior uveitis (14.3%), and intermediate uveitis (0.9%). Specific diagnosis was established in 51.6% of patients. The three most common specific diagnoses were Vogt-Koyanagi-Harada (VKH) disease (22.4%), followed by Behcet disease (6.7%) and herpetic anterior uveitis (5.8%). CONCLUSIONS: The most common type of noninfectious uveitis group was VKH, while herpetic anterior uveitis was the most common type of infectious uveitis in the central district of Thailand. PMID- 25111620 TI - Local protonation control using plasmonic activation. AB - Localized protonation of 4-mercaptopyridine (4-MPY), activated by light in the presence of silver nanoparticles is monitored under ambient conditions using surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering (TERS). The reaction can be controlled by the excitation wavelength and the atmospheric conditions, thus, providing a tool for site-specific control of protonation. PMID- 25111621 TI - Two pediatric liver transplantation guidelines issued by the American Association for the Study of Liver Diseases: A simple survey of their characteristics. PMID- 25111622 TI - Troponin T immunosensor based on liquid crystal and silsesquioxane-supported gold nanoparticles. AB - A nanostructured immunosensor based on the liquid crystal (E)-1-decyl-4-[(4 decyloxyphenyl)diazenyl]pyridinium bromide (Br-Py) and gold nanoparticles supported by the water-soluble hybrid material 3-n-propyl-4-picolinium silsesquioxane chloride (AuNP-Si4Pic(+)Cl(-)) was built for the detection of troponin T (cTnT), a cardiac marker for acute myocardial infarction (AMI). The functionalized nanostructured surface was used to bind anti-cTnT monoclonal antibodies through electrostatic interaction. The immunosensor (ab-cTnT/AuNP Si4Pic(+)Cl(-)/Br-Py/GCE) surface was characterized by microscopy techniques. The electrochemical behavior of the immunosensor was studied by cyclic voltammetry and electrochemical impedance spectroscopy. A calibration curve was obtained by square-wave voltammetry. The immnunosensor provided a limit of detection of 0.076 ng mL(-1) and a linear range between 0.1 and 0.9 ng mL(-1) (appropriate for AMI diagnosis). PMID- 25111623 TI - The reliability of routine clinical post-processing software in assessing potential diffusion-weighted MRI "biomarkers" in brain metastases, common mistake. PMID- 25111624 TI - MR spectroscopy in the diagnosis of bacterial etiology in brain abscesses. PMID- 25111626 TI - Response to "The reliability of routine clinical post-processing software in assessing potential diffusion weighted MRI biomarkers in brain metastases: common mistake". PMID- 25111625 TI - MR T(1)rho quantification of cartilage focal lesions in acutely injured knees: correlation with arthroscopic evaluation. AB - OBJECTIVE: Quantitative T1rho MRI has been suggested as a promising tool to detect changes in cartilage composition that are characteristic of cartilage damage and degeneration. The objective of this study was to evaluate the capability of MR T1rho to detect cartilage lesions as evaluated by arthroscopy in acutely ACL-injured knees and to compare with the Whole-Organ Magnetic Resonance Imaging Score (WORMS) using clinical standard MRI. METHOD: Ten healthy controls (mean age 35) with no ACL injury or history of osteoarthritis (OA) and 10 patients with acute ACL injuries (mean age 39) were scanned at 3 Tesla (3T). ACL patients underwent ACL reconstruction, where focal lesions were graded according to an Outerbridge grading system during arthroscopic evaluation. Normalized MR T1rho values (T1rho z-scores normalized to control values in matched regions) in full thickness, and superficial and deep layers of cartilage were compared between defined sub-compartments with and without focal lesions. Intraclass (ICC) correlation and the root mean square coefficient of variation (RMS-CV) were performed to evaluate the inter-observer reproducibility of T1rho quantification. Sub-compartments of cartilage were also evaluated using WORMS scoring and compared to their Outerbridge score respectively. RESULTS: The inter-observer ICC and the RMS-CV of the sub-compartment T1rho quantification were 0.961 and 3.9%, respectively. The average T1rho z-scores were significantly increased in sub compartments with focal lesions compared to those without focal lesions and to the control cohort (p<0.05). CONCLUSION: Our results indicate that T1rho provided a better diagnostic capability than clinical standard MRI grading in detecting focal cartilage abnormalities after acute injuries. Quantitative MRI may have great potential in detecting cartilage abnormalities and degeneration non invasively, which are occult with standard morphological MRI. PMID- 25111627 TI - Serine versus threonine glycosylation with alpha-O-GalNAc: unexpected selectivity in their molecular recognition with lectins. AB - The molecular recognition of several glycopeptides bearing Tn antigen (alpha-O GalNAc-Ser or alpha-O-GalNAc-Thr) in their structure by three lectins with affinity for this determinant has been analysed. The work yields remarkable results in terms of epitope recognition, showing that the underlying amino acid of Tn (serine or threonine) plays a key role in the molecular recognition. In fact, while Soybean agglutinin and Vicia villosa agglutinin lectins prefer Tn threonine, Helix pomatia agglutinin shows a higher affinity for the glycopeptides carrying Tn-serine. The different conformational behaviour of the two Tn biological entities, the residues of the studied glycopeptides in the close proximity to the Tn antigen and the topology of the binding site of the lectins are at the origin of these differences. PMID- 25111628 TI - Pigeon (Columba livia) and rat (Rattus norvegicus) performance in the midsession reversal procedure depends upon cue dimensionality. AB - Pigeons (Columba livia) produce many anticipatory and perseverative errors on discrimination tasks with a reversal of reward contingencies partway through the session. Prior comparative research has suggested that rats (Rattus norvegicus) do not show the same number of errors and produce results that more closely resemble those of humans. We examined pigeons' performance on a visual-spatial discrimination with the reversal point randomized within the session and found that they showed remarkably few errors. When these subjects were split into groups with the contingencies for reward unconfounded, the birds in the spatial contingency group maintained their performance, and those in the visual contingency group made many more anticipatory and perseverative errors. We also examined the performance of naive pigeons on a spatial midsession reversal task and found a pattern of results similar to those shown by pigeons that had previously been trained on a visual-spatial reversal procedure. Finally, we studied rats on a T-maze using a spatial-discrimination midsession reversal task and found that the rats showed a large number of anticipatory and perseverative errors. Near-perfect performance on the midsession reversal task appears to be subject to the ability of the animal to orient spatially during the intertrial interval, rather than being due to broad species differences. PMID- 25111629 TI - Personality structure in the domestic cat (Felis silvestris catus), Scottish wildcat (Felis silvestris grampia), clouded leopard (Neofelis nebulosa), snow leopard (Panthera uncia), and African lion (Panthera leo): a comparative study. AB - Although the study of nonhuman personality has increased in the last decade, there are still few studies on felid species, and the majority focus on domestic cats. We assessed the structure of personality and its reliability in five felids domestic cats, clouded leopards, snow leopards, African lions, and previous data on Scottish wildcats-and compared the results. In addition to the benefits of understanding more about this taxon, comparative studies of personality structure have the potential to provide information on evolutionary relationships among closely related species. Each of the species studied was found to have three factors of personality. Scottish wildcats' factors were labeled Dominance, Agreeableness, and Self Control; domestic cats' factors were Dominance, Impulsiveness, and Neuroticism; clouded leopards' factors were Dominance/Impulsiveness, Agreeableness/Openness, and Neuroticism; snow leopards' factors were Dominance, Impulsiveness/Openness, and Neuroticism; and African lions' factors were Dominance, Impulsiveness, and Neuroticism. The Neuroticism and Impulsiveness factors were similar, as were two of the Dominance factors. A taxon-level personality structure also showed three similar factors. Age and sex effects are also discussed. PMID- 25111630 TI - Shape from shading in starlings (Sturnus vulgaris). AB - Birds behave as if they quickly and accurately perceive an object-filled visual world. Beyond the extensive research with pigeons, however, there is a large and important gap in our knowledge about the mechanisms of object perception and recognition in other avian visual systems. The pattern of shading reflected from the surfaces of objects is one important optical feature that provides fundamental information about shape. To better understand how surface and object shading is processed by a passerine species, 5 starlings were tested with differentially illuminated convex and concave curved surfaces in 3 experiments using a simultaneous visual discrimination procedure. Starlings rapidly learned this shape-from-shading discrimination independent of varied lighting direction, surface color, and camera perspective. Variations in the pattern of lighting through experimental manipulations of camera perspective, surface height, contrast, material specularity, and surface shape were consistent with the hypothesis that the starlings perceived these illuminated surfaces as having 3 dimensional shape, similar to results previously collected with pigeons. These similarities across different orders of birds indicate that the relative shading of objects in a visual scene is a highly salient feature for shape processing in birds and is likely a highly conserved visual process that is widely distributed within this class of animal. PMID- 25111631 TI - Interspecific communication from people to horses (Equus ferus caballus) is influenced by different horsemanship training styles. AB - The ability of many domesticated animals to follow human pointing gestures to locate hidden food has led to scientific debate on the relative importance of domestication and individual experience on the origins and development of this capacity. To further explore this question, we examined the influence of different prior training histories/methods on the ability of horses (Equus ferus caballus) to follow a momentary distal point. Ten horses previously trained using one of two methods (ParelliTM natural horsemanship or traditional horse training) were tested using a standard object choice task. The results show that neither group of horses was initially able to follow the momentary distal point. However, after more experience with the point, horses previously trained using the Parelli natural horsemanship method learned to follow momentary distal points significantly faster than those previously trained with traditional methods. The poor initial performance of horses on distal pointing tasks, coupled with the finding that prior training history and experimental experience can lead to success on this task, fails to support the predictions of the domestication hypothesis and instead lends support to the two-stage hypothesis. PMID- 25111633 TI - Right anterior thoracotomy aortic valve replacement is associated with less cost than sternotomy-based approaches: a multi-institution analysis of 'real world' data. AB - BACKGROUND: Large institutional analyses demonstrating outcomes of right anterior mini-thoracotomy (RAT) for isolated aortic valve replacement (isoAVR) do not exist. In this study, a group of cardiac surgeons who routinely perform minimally invasive isoAVR analyzed a cross-section of US hospital records in order to analyze outcomes of RAT as compared to sternotomy. METHODS: The Premier database was queried from 2007-2011 for clinical and cost data for patients undergoing isoAVR. This de-identified database contains billing, hospital cost, and coding data from >600 US facilities with information from >25 million inpatient discharges. Expert rules were developed to identify patients with RAT and those with any sternal incision (aStern). Propensity matching created groups adjusted for patient differences. The impact of surgical approach on outcomes and costs was modeled using regression analysis and, where indicated, adjusting for hospital size and geographical differences. RESULTS: AVR was performed in 27,051 patients. Analysis identified isoAVR by RAT (n = 1572) and by aStern (n = 3962). Propensity matching created two groups of 921 patients. RAT was more likely performed in southern hospitals (63% vs 36%; p < 0.01), teaching hospitals (66% vs 58%; p < 0.01) and larger hospitals (47% vs 30%; p < 0.01). There was significantly less blood product cost associated with RAT ($1381 vs $1912; p < 0.001). After adjusting for hospital differences, RAT was associated with lower cost than aStern ($38,769 vs $42,656; p < 0.01). CONCLUSIONS: Outcomes analyses can be performed from hospital administrative collective databases. This real world analysis demonstrates comparable outcomes and less cost and ICU time with RAT for AVR. PMID- 25111634 TI - Costs and utilization of hemophilia A and B patients with and without inhibitors. AB - OBJECTIVE: To evaluate the health system costs among patients with hemophilia A and B with and without inhibitors over 5 years. METHODS: This was a retrospective, observational study utilizing medical and pharmacy electronic medical records and administrative encounters/claims data tracking US patients between 2006-2011. Patients with diagnosis codes for hemophilia A and B were identified. Patients with inhibitors were characterized by utilization of bypassing agents activated prothrombin complex concentrate or factor VIIa on two or more distinct dates. Severity was classified as mild, moderate, or severe based on laboratory tests of clotting factor. RESULTS: There were 160 hemophilia A patients and 54 hemophilia B patients identified. From this group, seven were designated as patients with inhibitors (five with hemophilia A and two with hemophilia B). Hemophilia A patients without inhibitors reported 65 (41.9%) as being severe, 19 (12.3%) as moderate, and 71 (45.8%) as mild. Hemophilia B patients without inhibitors reported nine (17.3%) had severe, 13 (25.0%) had moderate, and 30 (57.7%) had mild hemophilia. All patients with inhibitors had been hospitalized in the previous 5 years compared to 64 (41.3%) with hemophilia A without inhibitors and 22 (42.3%) with hemophilia B without inhibitors. The median aggregate cost per year (including factor and health resource use) was $325,780 for patients with inhibitors compared to $98,334 for hemophilia A patients without inhibitors and $23,265 for hemophilia B patients without inhibitors. CONCLUSIONS: The results suggest that, while the frequency of inhibitors within the hemophilia cohort was low, there was a higher frequency of hospitalizations, and the associated median aggregate costs per year were 3-fold higher than those patients without inhibitors. In contrast, hemophilia B patients experience less severe disease and account for lower aggregate yearly costs compared to either patients with hemophilia A or patients with inhibitors. PMID- 25111632 TI - Chemical interrogation of the malaria kinome. AB - Malaria, an infectious disease caused by eukaryotic parasites of the genus Plasmodium, afflicts hundreds of millions of people every year. Both the parasite and its host utilize protein kinases to regulate essential cellular processes. Bioinformatic analyses of parasite genomes predict at least 65 protein kinases, but their biological functions and therapeutic potential are largely unknown. We profiled 1358 small-molecule kinase inhibitors to evaluate the role of both the human and the malaria kinomes in Plasmodium infection of liver cells, the parasites' obligatory but transient developmental stage that precedes the symptomatic blood stage. The screen identified several small molecules that inhibit parasite load in liver cells, some with nanomolar efficacy, and each compound was subsequently assessed for activity against blood-stage malaria. Most of the screening hits inhibited both liver- and blood-stage malaria parasites, which have dissimilar gene expression profiles and infect different host cells. Evaluation of existing kinase activity profiling data for the library members suggests that several kinases are essential to malaria parasites, including cyclin-dependent kinases (CDKs), glycogen synthase kinases, and phosphoinositide 3-kinases. CDK inhibitors were found to bind to Plasmodium protein kinase 5, but it is likely that these compounds target multiple parasite kinases. The dual stage inhibition of the identified kinase inhibitors makes them useful chemical probes and promising starting points for antimalarial development. PMID- 25111635 TI - The characteristics of n- and p-type dopants in SnS2 monolayer nanosheets. AB - Based on density functional theory, the characteristics of n- and p-type impurities are investigated firstly by means of group V and VII atoms substituting sulfur atoms in the SnS2 monolayer nanosheets. Numerical results show that the formation energy and transition levels depend highly on the atomic size and electronegativity of the impurity atom. The formation energies increase with the increasing impurity atom size for each considered doping case. For group V atom-doped SnS2 monolayer nanosheet systems, the calculations of the transition level indicate that N, P or As doping is not effective for p-type conductivity. However, for group VII atom doping cases, F, Cl, Br and I impurities can offer effective n-type carriers in the SnS2 monolayer nanosheets. PMID- 25111638 TI - The first case of a patient with de novo partial distal 16q tetrasomy and a data's review. AB - We report on a patient with severe psychomotor disability, numerous dysmorphic features, and congenital malformations resulting from a complex genomic rearrangement on 16q24.1-q24.3 involving a de novo duplication-triplication pattern. To the best of our knowledge, this is the first reported patient presenting with this aberration within the distal chromosome 16q. We suggest that the clinical phenotype of our patient results from over-dosage of genes mapped to the region with duplication/triplication (five genes: FOXF1, FOXC2, ANKRD11, SPG7 and FANCA seem to play a peculiar role). Detailed molecular characterization and documentation of the complex genomic rearrangement observed in the proband and of the clinical presentation are important for accurate genotype-phenotype correlations in genetic counseling. Delineation of the gene map for the terminal region of chromosome 16q will provide insight into this chromosome 16q24.1-q24.3 contiguous gene duplication-triplication syndrome. PMID- 25111636 TI - Nanostructure embedded microchips for detection, isolation, and characterization of circulating tumor cells. AB - Circulating tumor cells (CTCs) are cancer cells that break away from either a primary tumor or a metastatic site and circulate in the peripheral blood as the cellular origin of metastasis. With their role as a "tumor liquid biopsy", CTCs provide convenient access to all disease sites, including that of the primary tumor and the site of fatal metastases. It is conceivable that detecting and analyzing CTCs will provide insightful information in assessing the disease status without the flaws and limitations encountered in performing conventional tumor biopsies. However, identifying CTCs in patient blood samples is technically challenging due to the extremely low abundance of CTCs among a large number of hematologic cells. To address this unmet need, there have been significant research endeavors, especially in the fields of chemistry, materials science, and bioengineering, devoted to developing CTC detection, isolation, and characterization technologies. Inspired by the nanoscale interactions observed in the tissue microenvironment, our research team at UCLA pioneered a unique concept of "NanoVelcro" cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with high efficiency. The working mechanism of NanoVelcro cell-affinity substrates mimics that of Velcro: when the two fabric strips of a Velcro fastener are pressed together, tangling between the hairy surfaces on two strips leads to strong binding. Through continuous evolution, three generations (gens) of NanoVelcro CTC chips have been established to achieve different clinical utilities. The first-gen NanoVelcro chip, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, was created for CTC enumeration. Side-by-side analytical validation studies using clinical blood samples suggested that the sensitivity of first-gen NanoVelcro chip outperforms that of FDA-approved CellSearch. In conjunction with the use of the laser microdissection (LMD) technique, second-gen NanoVelcro chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation. The individually isolated CTCs can be subjected to single-CTC genotyping (e.g., Sanger sequencing and next-generation sequencing, NGS) to verify the CTC's role as tumor liquid biopsy. Created by grafting of thermoresponsive polymer brushes onto SiNS, third gen NanoVelcro chips (i.e., Thermoresponsive NanoVelcro) have demonstrated the capture and release of CTCs at 37 and 4 degrees C, respectively. The temperature dependent conformational changes of polymer brushes can effectively alter the accessibility of the capture agent on SiNS, allowing for rapid CTC purification with desired viability and molecular integrity. This Account summarizes the continuous evolution of NanoVelcro CTC assays from the emergence of the original idea all the way to their applications in cancer research. We envision that NanoVelcro CTC assays will lead the way for powerful and cost-efficient diagnostic platforms for researchers to better understand underlying disease mechanisms and for physicians to monitor real-time disease progression. PMID- 25111639 TI - Influence on quality of life from an early cinacalcet prescription for secondary hyperparathyroidism in dialysis. AB - OBJECTIVE: The goal of this study is to compare patient-reported quality of life (PRQOL) evolution between two groups of end-stage renal disease patients with secondary hyperparathyroidism (SHPT). The first with a cinacalcet prescription within 3 months after a diagnosis of SHPT (early group) and a second group of patients with a later or no cinacalcet prescription (nonearly group). PATIENTS AND METHODS: From 2009 to 2012, we conducted a multicenter pharmaco-epidemiologic study in Lorraine region (France) including all consecutive patients on maintenance dialysis for at least 3 months with a diagnosis of SHPT (PTH > 500 pg/ml or first cinacalcet prescription). PRQOL was estimated using the Kidney Disease Quality Of Life-Short Form questionnaire, at baseline and at 6 and 12 months follow-up. Change in PRQOL was compared between the groups and adjusted with a propensity score. RESULTS: We included 124 patients: 44 in the early group and 80 in the nonearly group. The mental component summary score was lower in the early group, at baseline (43.6 +/- 6.6 vs 46.6 +/- 7.6; p = 0.030), and at the follow-up assessment (42.6 +/- 6.9 vs 45.7 +/- 7.9; p = 0.033). We found no difference between the groups in change in PRQOL, for all dimensions, even after adjustment with the propensity score. Mean serum alkaline phosphatase levels were normal in both groups at baseline (80.9 +/- 32.5 vs 95.1 +/- 39.6; p = 0.41). CONCLUSION: Cinacalcet prescription immediately following diagnosis of SHPT does not seem to be associated with better PRQOL evolution at 1 year. Mean serum alkaline phosphatase levels suggest that physicians should consider waiting for another PTH assay result before starting cinacalcet in case of a PTH rise. PMID- 25111640 TI - Ventilatory strategies in severe acute respiratory failure. AB - Lung-protective ventilator strategies are considered standard practice in the care of patients with the acute respiratory distress syndrome (ARDS). To minimize ventilator-induced lung injury, attention is directed at avoidance of alveolar overdistention and cyclical opening and closing. The lowest possible plateau pressure and tidal volume (V(T)) should be selected. A reasonable target V(T) in all mechanically ventilated patients is 6 mL/kg. A topic of much controversy is the optimal setting of positive end-expiratory pressure (PEEP). Results of a meta analysis using individual patient data from three randomized controlled trials suggest that higher PEEP should be used for moderate and severe ARDS, whereas lower PEEP may be more appropriate in patients with mild ARDS. PEEP should be set to maximize alveolar recruitment while avoiding overdistention. Volume and pressure limitation during mechanical ventilation can be described in terms of stress and strain. Fraction of inspired oxygen (Fio(2)) and PEEP are typically titrated to maintain arterial oxygen saturation (Spo(2)) of 88 to 95% (Pao(2) 55 80 mm Hg). There is currently no clear proven benefit for advanced modes. PMID- 25111641 TI - Ventilatory strategies in obstructive lung disease. AB - Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation (EFL) due to progressive airflow obstruction. The various mechanisms that cause EFL are central to understanding the physiopathology of COPD. At the end of expiration, dynamic inflation may occur due to incomplete emptying the lungs. This "extra" volume increases the alveolar pressure at the end of the expiration, resulting in auto-positive end-expiratory pressure (PEEP) or PEEPi. Acute exacerbations of COPD may result in increased airway resistance and inspiratory effort, further leading to dynamic hyperinflation. COPD exacerbations may be triggered by environmental exposures, infections (viral and bacterial), or bronchial inflammation, and may result in worsening respiratory failure requiring mechanical ventilation (MV). Acute exacerbations of COPD need to be distinguished from other events such as cardiac failure or pulmonary emboli. Strategies to treat acute respiratory failure (ARF) in COPD patients include noninvasive ventilation (NIV), pressure support ventilation, and tracheal intubation with MV. In this review, we discuss invasive and noninvasive techniques to address ARF in this patient population. When invasive MV is used, settings should be adjusted in a way that minimizes hyperinflation, while providing reasonable gas exchange, respiratory muscle rest, and proper patient-ventilator interaction. Further, weaning from MV may be difficult in these patients, and factors amenable to pharmacological correction (such as increased bronchial resistance, tracheobronchial infections, and heart failure) are to be systematically searched and treated. In selected patients, early use of NIV may hasten the process of weaning from MV and improve outcomes. PMID- 25111642 TI - Sedation and analgesia in mechanical ventilation. AB - Traditionally, critically ill patients undergoing mechanical ventilation (MV) have received sedation. Over the last decade, randomized controlled trials have questioned continued use of deep sedation. Evidence shows that a nurse-driven sedation protocol reduces length of MV compared with standard strategy with sedation. Furthermore, daily interruption of sedation reduces length of MV, intensive care unit (ICU), and hospital length of stay (LOS). A larger scale trial with daily interruption of sedation has confirmed these findings and furthermore showed a reduction in 1-year mortality with the use of daily interruption of sedation. Recently, a strategy with no sedation has been described reporting a reduction in length of MV, ICU, and hospital LOS compared with a strategy with daily interruption of sedation. Follow-up trials report that reducing sedation does not seem to increase the risk of psychological morbidity. Moreover, delirium has gained increased focus in recent years with development of validated tools to detect both hyperactive and hypoactive forms of delirium. Using validated tools for detecting delirium is important in monitoring and detecting acute brain dysfunction in critically ill patients. Evidence from randomized trials also cites a beneficial effect of early mobilization with respect to length of MV and delirium. PMID- 25111643 TI - Ventilator-associated pneumonia. AB - Ventilator-associated pneumonia (VAP) is an iatrogenic pulmonary infection that develops in tracheally intubated patients on mechanical ventilation for at least 48 hours. VAP is the nosocomial infection with the greatest impact on patient outcomes and health care costs. Endogenous colonization by aerobic gram-negative pathogens, that is, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus play a pivotal role in the pathogenesis of VAP. Several preventive strategies have shown efficacy in decreasing VAP incidence and are often implemented altogether as a prevention bundle. In patients with clinical suspicion of VAP, respiratory samples should be promptly collected. The empiric treatment should be based on the local prevalence of pathogens, duration of hospital stay, and prior antimicrobial therapy. The antibiotics can be stopped or adjusted to more narrow-spectrum once cultures and susceptibilities are available. PMID- 25111644 TI - Tracheostomy in mechanical ventilation. AB - Airway access for mechanical ventilation (MV) can be provided either by orotracheal intubation (OTI) or tracheostomy tube. During episodes of acute respiratory failure, patients are commonly ventilated through an orotracheal tube that represents an easy and rapid initial placement of the airway device. OTI avoids acute surgical complications such as bleeding, nerve and posterior tracheal wall injury, and late complications such as wound infection and tracheal lumen stenosis that may emerge due to tracheostomy tube placement. Tracheostomy is often considered when MV is expected to be applied for prolonged periods or for the improvement of respiratory status, as this approach provides airway protection, facilitates access for secretion removal, improves patient comfort, and promotes progression of care in and outside the intensive care unit (ICU). The aim of this review is to assess the frequency and performance of different surgical or percutaneous dilational tracheostomy and timing and safety procedures associated with the use of fiberoptic bronchoscopy and ultrasounds. Moreover, we analyzed the performance based on National European surveys to assess the current tracheostomy practice in ICUs. PMID- 25111645 TI - Noninvasive ventilation for patients with hypoxemic acute respiratory failure. AB - Noninvasive ventilation (NIV) has an established efficacy to improve gas exchange and reduce the work of breathing in patients with hypoxemic acute respiratory failure. The clinical efficacy in terms of meaningful outcome is less clear and depends very much on patient selection and assessment of the risks of the technique. The potential risks include an insufficient reduction of the oxygen consumption of the respiratory muscles in case of shock, an excessive increase in tidal volume in case of lung injury, and a risk of delayed or emergent intubation. With a careful selection of patients and a rapid decision regarding the need for intubation in case of failure, great benefits can be offered to patients. Emerging indications include its use in patients with treatment limitations, in the postoperative period, and in patients with immunosuppression. This last indication will necessitate reappraisal because the prognosis of the conditions associated with immunosuppression has improved over the years. In all cases, there is both a time window and a severity window for NIV to work, after which delaying endotracheal intubation may worsen outcome. The preventive use of NIV seems promising in this setting but needs more research. An emerging interesting new option is the use of high flow humidified oxygen, which seems to be intermediate between oxygen alone and NIV. PMID- 25111646 TI - Noninvasive ventilation in acute hypercapnic respiratory failure. AB - Noninvasive mechanical ventilation (NIV) improves gas exchange and clinical outcome in various types of acute respiratory failure. Acute exacerbation of chronic obstructive pulmonary disease is a frequent cause of acute hypercapnic respiratory failure (AHRF). According to several randomized controlled trials, the addition of NIV to standard medical therapy reduces mortality, intubation rate, and hospital length of stay in these patients. Indications for the use of NIV have expanded over the past decade. In this article, we discuss the clinical indications and goals of NIV in the management of AHRF. PMID- 25111647 TI - Noninvasive ventilation in withdrawal from mechanical ventilation. AB - Patients with chronic airflow obstruction and difficult or prolonged weaning are at increased risk for prolonged invasive mechanical ventilation (IMV). Several randomized controlled trials mainly conducted in patients who had pre-existing lung disease have shown that the use of noninvasive ventilation (NIV) to advance extubation in patients with difficult and prolonged weaning can result in reduced periods of endotracheal intubation, complication rates, and improved survival. Patients in these studies were hemodynamically stable, with a normal level of consciousness, no fever, and a preserved cough reflex. The use of NIV in the management of mixed populations with respiratory failure after extubation, including small proportions of chronic respiratory patients did not show clinical benefits included. By contrast, NIV immediately after extubation is effective in avoiding respiratory failure after extubation and improving survival in patients at risk for this complication, particularly those with chronic respiratory disorders, cardiac comorbidity, and hypercapnic respiratory failure. Finally, both continuous positive airway pressure and NIV can improve clinical outcomes in patients with postoperative acute respiratory failure, particularly abdominal and thoracic surgery. PMID- 25111648 TI - Extracorporeal support for severe acute respiratory failure. AB - Extracorporeal membrane oxygenation (ECMO) and extracorporeal CO(2) removal (ECCO(2)R) techniques have increasingly been applied in patients with severe acute lung injury refractory to conventional mechanical ventilatory support. The objectives of this article are to review current concepts of extracorporeal life support techniques (ECMO and ECCO(2)R systems) and provide the rationale for their application in patients with acute respiratory distress syndrome, chronic obstruction pulmonary disease, and as adjunctive therapy for bridging patients to lung transplantation. PMID- 25111649 TI - Late prematurity in twins: a Polish multicenter study. AB - The study aimed at investigating the impact of late prematurity (LPT) on neonatal outcome in twins and neonatal morbidity and mortality within LPT with regard to the completed weeks of gestation. The study was conducted in six tertiary obstetric departments from different provinces of Poland (Warsaw, Lublin, Poznan, Wroclaw, Bytom). It included 465 twin deliveries in the above centers in 2012. A comparative analysis of maternal factors, the course of pregnancy and delivery and neonatal outcome between LPT (34 + 0-36 + 6 weeks of gestation) and term groups (completed 37 weeks) was performed. The neonatal outcome included short term morbidities. The analysis of neonatal complication rates according to completed gestational weeks was carried out. Out of 465 twin deliveries 213 (44.8%) were LPT and 156 (33.55%) were term. There were no neonatal deaths among LPT and term twins. One-third of LPT newborns suffered from respiratory disorders or required antibiotics, 40% had jaundice requiring phototherapy, and 30% were admitted to NICU. The analysis of neonatal morbidity with regard to each gestational week at delivery showed that most analyzed complications occurred less frequently with the advancing gestational age, especially respiratory disorders and NICU admissions. The only two factors with significant influence on neonatal morbidity rate were neonatal birth weight (OR = 0.43, 95% CI = 0.2-0.9, p = .02) and gestational age at delivery (OR = 0.62, 95% CI = 0.5-0.8, p < .01). LPT have a higher risk of neonatal morbidity than term twins. Gestational age and neonatal birth weight seem to play a crucial role in neonatal outcome in twins. PMID- 25111652 TI - Responses of 9 lepidopteran species to Bacillus thuringiensis: How useful is phylogenetic relatedness for selecting surrogate species for nontarget arthropod risk assessment? AB - To evaluate phylogenetic relatedness as a proxy for susceptibility to Bacillus thuringiensis (Bt) when selecting species to act as surrogates for others in prerelease testing, we examined the responses of 11 laboratory-reared lepidopteran colonies, comprising members of 2 families, 5 genera, and 9 species, to a commercial Bt preparation. Survival, pupal mass, and timing of pupation and adult emergence of 2 noctuids (Spodoptera litura and Helicoverpa armigera) and 7 tortricids (Cnephasia jactatana, Ctenopseustis obliquana, Ctenopseustis herana,Planotortrix octo, Planotortrix notophaea,Planotortrix excessana [2 different laboratory colonies], and Epiphyas postvittana [2 colonies]) were examined after feeding first instar larvae with artificial diet containing 5 MUL/100 mL Dipel ES (Bt subsp. kurstaki). Bt caused significant larval mortality in all species except S. litura, in which only pupation was delayed compared with untreated controls. Neither of the noctuid species tested would act as a suitable surrogate for the other in tests of Bt impacts on survival. With the exception of the 2 colonies of E. postvittana, which differed from each other not only in their responses to Bt but also in their development times when not treated with Bt, species within each tortricid genus had similar responses to Bt and thus could act as surrogates for each other. Members of different genera within this family could represent each other only if relatively coarse measurement endpoints (e.g., toxic or not) were considered adequate for assessing risks to nontarget species in the field. PMID- 25111650 TI - Nuclear overhauser enhancement mediated chemical exchange saturation transfer imaging at 7 Tesla in glioblastoma patients. AB - BACKGROUND AND PURPOSE: Nuclear Overhauser Enhancement (NOE) mediated chemical exchange saturation transfer (CEST) is a novel magnetic resonance imaging (MRI) technique on the basis of saturation transfer between exchanging protons of tissue proteins and bulk water. The purpose of this study was to evaluate and compare the information provided by three dimensional NOE mediated CEST at 7 Tesla (7T) and standard MRI in glioblastoma patients. PATIENTS AND METHODS: Twelve patients with newly diagnosed histologically proven glioblastoma were enrolled in this prospective ethics committee-approved study. NOE mediated CEST contrast was acquired with a modified three-dimensional gradient-echo sequence and asymmetry analysis was conducted at 3.3 ppm (B1 = 0.7 uT) to calculate the magnetization transfer ratio asymmetry (MTR(asym)). Contrast enhanced T1 (CE-T1) and T2-weighted images were acquired at 3T and used for data co-registration and comparison. RESULTS: Mean NOE mediated CEST signal based on MTR(asym) values over all patients was significantly increased (p<0.001) in CE-T1 tumor (-1.99 +/- 1.22%), tumor necrosis (-1.36 +/- 1.30%) and peritumoral CEST hyperintensities (PTCH) within T2 edema margins (-3.56 +/- 1.24%) compared to contralateral normal appearing white matter (-8.38 +/- 1.19%). In CE-T1 tumor (p = 0.015) and tumor necrosis (p<0.001) mean MTR(asym) values were significantly higher than in PTCH. Extent of the surrounding tumor hyperintensity was smaller in eight out of 12 patients on CEST than on T2-weighted images, while four displayed at equal size. In all patients, isolated high intensity regions (0.40 +/- 2.21%) displayed on CEST within the CE-T1 tumor that were not discernible on CE-T1 or T2-weighted images. CONCLUSION: NOE mediated CEST Imaging at 7 T provides additional information on the structure of peritumoral hyperintensities in glioblastoma and displays isolated high intensity regions within the CE-T1 tumor that cannot be acquired on CE-T1 or T2-weighted images. Further research is needed to determine the origin of NOE mediated CEST and possible clinical applications such as therapy assessment or biopsy planning. PMID- 25111654 TI - The National ALS Registry: a recruitment tool for research. AB - INTRODUCTION: Subject recruitment is critical for understanding fatal diseases like ALS, however linking patients with researchers can be challenging. The U.S. population-based National ALS Registry allows recruitment of persons with ALS (PALS) for research opportunities. METHODS: The Registry's Research Notification Mechanism was used to recruit PALS aged >=21 years; participants completed a Web based epidemiologic survey. PALS (n = 2,232) were sent an email describing the study, and 268 surveys were completed. RESULTS: The mean age (+/- SD) of eligible participants was 57.7 +/- 9.3 years for men and 61.5 +/- 8.9 for women. Most were men (63%) and Caucasian (92%). Of 256 potentially eligible participants, 37.5% (n = 96) returned an authorization to disclose protected health information. ALS was confirmed for 94% (83/88) from physician responses. CONCLUSIONS: This analysis demonstrates the National ALS Registry's usefulness in recruiting PALS for research. This recruitment source can potentially foster the discovery of better treatment options and therapies, and of prevention strategies. PMID- 25111656 TI - Post-traumatic olfactory loss: psychophysical, electrophysiological and neuroradiological findings in three single case studies. AB - BACKGROUND: Traumatic brain injury is one of the main causes of smell disorders. The degree of olfactory loss may vary and depend on the severity, nature and location of injury within the olfactory system. The diagnosis of disorders of the sense of smell is based on medical history and clinical data supported by psychophysical tests of smell, electrophysiological and neuroimaging measures. METHODS: This study reports three single clinical cases of post-traumatic anosmia evaluated by Sniffin' Sticks Test, Olfactory Event-Related Potential and Magnetic Resonance Imaging examinations. RESULTS: The Olfactory Event-Related Potential findings confirmed the presence of functional olfactory impairment in all three post-traumatic patients showing a good correlation with results of the psychophysical testing. In particular, Sniffin' Sticks Test and OERPs allowed to demonstrate the functional nature of post-traumatic olfactory loss, while the MRI identified the location and extent of injury compatible with the olfactory disorder. CONCLUSIONS: OERPs may have a good clinical application in objective diagnosis of post-traumatic anosmia, especially when the neuroradiological examination does not show lesions compatible with olfactory loss. PMID- 25111655 TI - Somatostatin analogues for receptor targeted photodynamic therapy. AB - Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6 K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo vasculature. These results show that conjugate 1 might have potential as an in vivo sst2 targeting photosensitizer conjugate. PMID- 25111657 TI - Definition and applications of a versatile chemical pollution footprint methodology. AB - Because of the great variety in behavior and modes of action of chemicals, impact assessment of multiple substances is complex, as is the communication of its results. Given calls for cumulative impact assessments, we developed a methodology that is aimed at expressing the expected cumulative impacts of mixtures of chemicals on aquatic ecosystems for a region and subsequently allows to present these results as a chemical pollution footprint, in short: a chemical footprint. Setting and using a boundary for chemical pollution is part of the methodology. Two case studies were executed to test and illustrate the methodology. The first case illustrates that the production and use of organic substances in Europe, judged with the European water volume, stays within the currently set policy boundaries for chemical pollution. The second case shows that the use of pesticides in Northwestern Europe, judged with the regional water volume, has exceeded the set boundaries, while showing a declining trend over time. The impact of mixtures of substances in the environment could be expressed as a chemical footprint, and the relative contribution of substances to that footprint could be evaluated. These features are a novel type of information to support risk management, by helping prioritization of management among chemicals and environmental compartments. PMID- 25111658 TI - Baseline adherence to the Mediterranean diet and major cardiovascular events: Prevencion con Dieta Mediterranea trial. PMID- 25111659 TI - Subgroups of familial and aggressive prostate cancer with considerable frequencies of BRCA2 mutations. AB - BACKGROUND: One of the known risk factors for prostate cancer (PrCa) is germline mutations in the BRCA2 gene. Previous searches for clinical characteristics which could identify a subgroup of patients enriched for mutation carriers revealed early onset and aggressive PrCa as useful parameters, but they are rather unspecific. METHODS: Identification of BRCA2 mutation carriers by sequencing all exons of BRCA2 in a German cohort of 382 familial PrCa cases and of 92 sporadic PrCa cases with early onset (<=60 years). To define a subgroup of PrCa patients enriched for BRCA2 mutation carriers, we used clinical parameters including a detailed family history (FH) for PrCa and breast cancer. RESULTS: Five BRCA2 mutations and ten variants of unknown significance (VUS) were identified. While the VUS were evenly distributed among the groups, mutation carriers were lacking from the sporadic cases and over represented among familial cases with aggressive disease. High prostate specific antigen (PSA) at diagnosis (>20 ng/ml) was the only criterion with significant enrichment of mutation carriers (6.4%, P = 0.0005). In men with aggressive disease, death from PrCa (6.3% including FH of lethal PrCa; P = 0.05) and FH of both prostate and breast cancer (4.8%; P = 0.3) increased the frequency of mutation carriers. Larger studies and/or meta-analyses are needed to validate these parameters. CONCLUSIONS: We have identified three potentially useful criteria, high PSA, death from PrCa (patient or FH), and aggressive PrCa in combination with FH of breast and prostate cancer. If confirmed, they may become useful for the decision which patients may benefit from BRCA2 testing. PMID- 25111660 TI - The berry constituents quercetin, kaempferol, and pterostilbene synergistically attenuate reactive oxygen species: involvement of the Nrf2-ARE signaling pathway. AB - Quercetin, kaempferol, and pterostilbene are abundant in berries. The anti oxidative properties of these constituents may contribute to cancer chemoprevention. However, their precise mechanisms of action and their combinatorial effects are not completely understood. Nuclear factor (erythroid derived 2)-like 2 (Nrf2) regulates anti-oxidative stress enzymes and Phase II drug metabolizing/detoxifying enzymes by binding to antioxidant response element (ARE). This study aimed to investigate the anti-oxidative stress activities of quercetin, kaempferol, and pterostilbene individually and in combination, as well as the involvement of the Nrf2-ARE signaling pathway. Quercetin, kaempferol, and pterostilbene all exhibited strong free-radical scavenging activity in the DPPH assay. The MTS assay revealed that low concentration combinations we tested were relatively non-toxic to HepG2-C8 cells. The results of the DCFH-DA assay and combination index (CI) indicated that quercetin, kaempferol, and pterostilbene attenuated intracellular reactive oxygen species (ROS) levels when pretreated individually and had synergistic effects when used in combination. In addition, the combination treatment significantly induced ARE and increased the mRNA and protein expression of Nrf2-regulated genes. Collectively, our study demonstrated that the berry constituents quercetin, kaempferol, and pterostilbene activated the Nrf2-ARE signaling pathway and exhibited synergistic anti-oxidative stress activity at appropriate concentrations. PMID- 25111661 TI - Metallothioneins attenuate paraquat-induced acute lung injury in mice through the mechanisms of anti-oxidation and anti-apoptosis. AB - Paraquat (PQ) is a widely used herbicide, and lung is the primary target of PQ poisoning. Metallothionein (MT) is a potent antioxidant and free radical scavenger, and has been shown to play a protective role in lung injury induced by different stressors. This study was undertaken to evaluate the protective potential of MT against PQ-induced acute lung injury using MT-I/II null (MT(-/-)) mice. Wild-type (MT(+/+)) mice and MT(-/-) mice were given one intragastric administration of 50mg/kg PQ for 24h, and it was revealed that MT(-/-) mice were more susceptible to PQ-induced acute lung injury than MT(+/+) mice evidenced by the following findings. As compared with MT(+/+) mice, MT(-/-) mice presented more severe histopathological lesions in the lung, higher pulmonary malondialdehyde content, and more reduced pulmonary antioxidative enzymes activities. PQ also induced more apoptosis in pneumocytes from MT(-/-) mice, and the expressions of apoptosis-related proteins Bax, Bcl-2, cleaved-caspase-3, and the ratio of Bax/Bcl-2 were all more significantly increased in PQ-treated MT(-/ ) mice. Our results clearly demonstrate that endogenous MT can attenuate PQ induced acute lung injury, possibly through the mechanisms of anti-oxidation and anti-apoptosis. PMID- 25111662 TI - Coordination of care between health and education systems for patients with a hematologic or oncologic diagnosis: a time study analysis. AB - Given the increasing emphasis on care coordination between healthcare and schools, hospital-school liaison services are increasing in demand. Limited research examines hospital-school liaison programs that focus on educational journeys of school-age patients with a chronic illness. Thus, this initiative aimed to determine the time needed to support the educational needs of these patients. Liaisons tracked time spent per patient, and per specific task category, to support school-age patients (N=419) using work-sampling and time-and motion methods. Findings may be useful for hospital-based programs seeking to establish or increase staff dedicated to the coordination of care between school and healthcare systems. PMID- 25111663 TI - Available resources and challenges for the clinical annotation of somatic variations. AB - Next-generation sequencing (NGS) has become an important tool for identifying clinically relevant variants in both inherited disorders and oncology. Variants annotation that enables the creation of meaningful clinical reports often requires mining multiple publicly available databases. There are a number of such resources that have been designed to catalog and mine a plethora of germline variants or mutations. However, when analyzing tumor specimens in clinical settings, one may need to use different or ancillary resources that are specific for somatic variants or actionable mutations that may have clinical or treatment implications. The purpose of this review is to recapitulate the state of the art of somatic variation databases, which can aid in the clinical interpretation of NGS-based assays in oncology. In addition, the current need for collating various annotation sources into one-stop solutions to facilitate faster query execution and better integration into existing laboratory information systems are discussed. PMID- 25111664 TI - On the precision of goal-directed attentional selection. AB - Attention selects objects in a scene for cognitive processing. A growing body of evidence has been used to argue that observers are able to narrowly restrict attentional selection to stimuli that match a feature-based target template while ignoring similar-looking distractors. For example, visual search for a target among feature-similar nontargets is highly efficient. Here, I demonstrate that observers are substantially impaired at selecting a target among feature-similar nontargets when stimuli are compared with a target template serially in time. The results argue that goal-directed attentional selection is distinctly imprecise, and that comparing stimuli with a target template reflects an inefficient mechanism of selection that cannot fully explain visual search performance under demanding conditions. PMID- 25111665 TI - Pitch structure, but not selective attention, affects accent weightings in metrical grouping. AB - Among other cues, pitch and temporal accents contribute to grouping in musical sequences. However, exactly how they combine remains unclear, possibly because of the role of structural organization. In 3 experiments, participants rated the perceived metrical grouping of sequences that either adhered to the rules of tonal Western musical pitch structure (musical key) or did not (atonal). The tonal status of sequences did not provide any grouping cues and was irrelevant to the task. Experiment 1 established equally strong levels of pitch leap accents and duration accents in baseline conditions, which were then recombined in subsequent experiments. Neither accent type was stronger or weaker for tonal and atonal contexts. In Experiment 2, pitch leap accents dominated over duration accents, but the extent of this advantage was greater when sequences were tonal. Experiment 3 ruled out an attentional origin of this effect by replicating this finding while explicitly manipulating attention to pitch or duration accents between participant groups. Overall, the presence of tonal pitch structure made the dimension of pitch more salient at the expense of time. These findings support a dimensional salience framework in which the presence of organizational structure prioritizes the processing of the more structured dimension regardless of task relevance, independent from psychophysical difficulty, and impervious to attentional allocation. PMID- 25111666 TI - Selection history modulates the effects of dual mechanisms on flanker interference. AB - The limit of processing capacity and the effectiveness of top-down control are 2 mechanisms that underlie distractor interference in a flanker task. The current study investigates how the interblock selection history shaped by the target number and the predictability of distractor location may modulate the effects of these 2 mechanisms on flanker interference. Experiment 1 showed that the distractor compatibility effect was eliminated when the task array contained 4 or 5 identical targets, which reflected the capacity limit. The target number and distractor location's predictability (Experiment 2) or location predictability and target-distractor proximity (Experiment 3) were manipulated across blocks, while compatibility varied within blocks, with control efficacy underlying the effects of distractor location (predictability and proximity). The interblock selection history was induced by task order, beginning with 2 or 4 targets in Experiment 2 and with a distractor at a fixed or an unpredictable location in Experiment 3. Effects of interblock selection history were found when the intertrial context did not promote an incentive for altering the processing mode. When the incentive for enacting top-down control is high, intertrial contextual factors influence flanker interference. Contextual factors related to the target number and distractor location modulate flanker interference at multiple levels. PMID- 25111667 TI - A randomized, placebo-controlled, double-blind trial on the management of post infective cough by inhaled ipratropium and salbutamol administered in combination. AB - Post-viral cough is a type of cough originating from upper respiratory tract infections that persists after the infection is resolved. Although it was hypothesized that bronchodilators might have a role in the management of post viral cough, a clear demonstration of their efficacy is missing. Therefore, we tested the efficacy of a combination of a beta-agonist and an anticholinergic agent in reducing post-viral cough with a randomized, double blind, placebo controlled clinical trial. Patients were treated for 10 days with either a nebulized combination of salbutamol 1.875 mg/0.5 mL and ipratropium bromide 0.375 mg/0.5 mL, or a placebo, and followed up for another 10 days. Daytime and nighttime cough severity and spirometry testing were assessed before starting treatment, after 10 and 20 days. Ninety-two patients were randomized to receive placebo (n = 46) or the active treatment (n = 46); nine of them (4 in the placebo group, 5 in the active treatment group) dropped out from the study. Daytime and nighttime cough severity were significantly reduced in both groups during the study period, but the reduction was more prominent in the active treatment group vs. placebo after 10 days of treatment (P = 0.003 for day cough; P = 0.061 for night cough), whereas at the end of follow-up period cough severity was comparable between the two groups. Small but significant increases in spirometric parameters were observed in the active treatment vs. placebo group, although at the end of follow-up these values returned to be comparable to placebo. The frequency of adverse events was not significantly different between the two groups of patients. We concluded that a combination of a beta-agonist and an anticholinergic agent can effectively reduce post-viral cough, and can thus represent a valid option for this type of cough. PMID- 25111668 TI - Factors associated with postoperative hypothyroidism after lobectomy in papillary thyroid microcarcinoma patients. AB - PURPOSE: No previous study regarding the correlation between post-operative thyroid function and underlying thyroid histopathology has been published. This study assessed the relationship between postoperative thyroid function after lobectomy and multiple factors in papillary thyroid microcarcinoma (PTMC) patients. MATERIALS AND METHODS: From January 2010 to December 2010, 338 patients who had undergone thyroid lobectomy for PTMC were enrolled. Patients with pre operative hyperthyroidism or those with hypothyroidism but no pre-operative serological data were excluded, leaving a cohort of 285 patients. The relationships between post-operative thyroid function (based on successful cessation of thyroxine replacement therapy) and multiple factors (patient age and sex, serological data, the Pre-operative anteroposterior diameter of the thyroid gland, underlying histopathology of the thyroid gland, and number of attempts to stop thyroxine replacement therapy) were analyzed. RESULTS: Out of 285 patients, 157 attempted to stop thyroxine replacement therapy once or twice after lobectomy; 91 successfully stopped thyroxine replacement therapy during the study period. The final histopathologic diagnoses after surgery included Hashimoto's thyroiditis (n = 5), non-Hashimoto type of lymphocytic thyroiditis (n = 17), and normal thyroid parenchyma (n = 135). Pre-operative thyroid-stimulating hormone (TSH) levels differed significantly between patients with postoperative hypothyroidism and those with postoperative euthyroidism (univariate logistic regression analysis, p = 0.0028; multivariate logistic regression analysis, p = 0.0029). No statistically significant differences were found for any other factors. CONCLUSIONS: The study results demonstrated that the Pre-operative TSH level was the only predictor for the development of post-operative hypothyroidism after thyroid lobectomy in PTMC patients. PMID- 25111669 TI - Synthesis of cyclic imides from nitriles and diols using hydrogen transfer as a substrate-activating strategy. AB - An atom-economical and versatile method for the synthesis of cyclic imides from nitriles and diols was developed. The method utilizes a Ru-catalyzed transfer hydrogenation reaction in which the substrates, diols, and nitriles are simultaneously activated into lactones and amines in a redox-neutral manner to afford the corresponding cyclic imides with evolution of H2 gas as the sole byproduct. This operationally simple and catalytic synthetic method provides a sustainable and easily accessible route to cyclic imides. PMID- 25111670 TI - Maternal mood and concordant maternal and infant salivary cortisol during heel lance while in kangaroo care. AB - BACKGROUND: Maternal kangaroo care (MKC) is a naturalistic intervention that alleviates neonatal pain, and mothers are assumed to play a stress regulatory role in MKC. Yet, no MKC infant pain study has examined relationship between maternal and infant stress reactivity concurrently, or whether post-partum depression and/or anxiety (PPDA) alters maternal and neonatal stress response and the regulatory effects of MKC. OBJECTIVES: To examine the concordance of salivary cortisol reactivity between 42 mothers and their stable preterm infants during routine infant heel lance (HL) while in MKC and to compare salivary cortisol between groups of mothers with and without PPDA and their infants. METHODS: Maternal and infant salivary cortisol samples were collected pre-HL and 20 min post-HL with two additional maternal samples at night and in the morning. Mothers and infants were allocated to with PPDA versus without PPDA study groups on the basis of maternal post-natal mental health assessment scores. RESULTS: Higher mothers' cortisol pre-HL was weakly associated with higher infants' salivary cortisol in response to the HL procedure. Maternal depression and/or anxiety were not associated with infants' cortisol. During HL, both groups of mothers and infants showed no change in salivary cortisol. CONCLUSIONS: Concordance between mother and infant salivary cortisol supports the maternal stress regulatory role in MKC. MKC may have stress regulatory benefits for mothers and their preterm infants during HL independent of PPDA. Future MKC studies that target mothers with altered mood will help to build on these findings. PMID- 25111673 TI - Implementation of a new screening recommendation in health care: the Veterans Health Administration's approach to lung cancer screening. PMID- 25111672 TI - Small regulatory RNAs in lambdoid bacteriophages and phage-derived plasmids: Not only antisense. AB - Until recently, only two small regulatory RNAs encoded by lambdoid bacteriophages were known. These transcripts are derived from paQ and pO promoters. The former one is supposed to act as an antisense RNA for expression of the Q gene, encoding a transcription antitermination protein. The latter transcript, called oop RNA, was initially proposed to have a double role, in establishing expression of the cI gene and in providing a primer for DNA replication. Although the initially proposed mechanisms by which oop RNA could influence the choice between two alternative developmental pathways of the phage and the initiation of phage DNA replication were found not true, the pO promoter has been demonstrated to be important for both regulation of phage development and control of DNA replication. Namely, the pO-derived transcript is an antisense RNA for expression of the cII gene, and pO is a part of a dual promoter system responsible for regulation of initiation of DNA synthesis from the orilambda region. Very recent studies identified a battery of small RNAs encoded by lambdoid bacteriophages existing as prophages in chromosomes of enterohemorrhagic Escherichia coli strains. Some of them have very interesting functions, like anti-small RNAs. PMID- 25111671 TI - The roles of microphthalmia-associated transcription factor and pigmentation in melanoma. AB - MITF and pigmentation play important roles in both normal melanocyte and transformed melanoma cell biology. MITF is regulated by many pathways and it also regulates many targets, some of which are still being discovered and functionally validated. MITF is involved in a wide range of processes in melanocytes, including pigment synthesis and lineage survival. Pigmentation itself plays an important role as the interface between genetic and environmental factors that contribute to melanoma. PMID- 25111674 TI - Giant condyloma acuminatum in the axilla. PMID- 25111675 TI - Cluster size effects of platinum oxide as active sites in hydrogen evolution reactions. AB - The successful design of photocatalytic hydrogen generation from water relies on a thorough understanding of the role of cocatalyst. The photoreactivity was studied as a function of the cluster size of the oxidized platinum cocatalyst. The maximum turnover frequency is found on the smallest-sized cocatalyst. This effect can be attributed to the size-dependent proton adsorption. PMID- 25111676 TI - Redescription of Sarcocystis fusiformis sarcocysts from the water buffalo (Bubalus bubalis). AB - Four valid species of Sarcocystis have been reported from the water buffalo (Bubalus bubalis): Sarcocystis fusiformis, Sarcocystis buffalonis, Sarcocystis levinei and Sarcocystis dubeyi. Here, we redescribe structure of S. fusiformis sarcocysts by scanning and transmission electron microscopy (SEM, TEM). Twenty one macroscopic sarcocysts from oesophagus of the water buffalo in Egypt were examined by light microscopy, SEM and TEM. The sarcocyst wall was up to 9 MUm thick, depending on the section and the technique. In 5 MUm paraffin-embedded sections, the sarcocyst wall was indistinct, 2-5 MUm thick and appeared smooth. In 1 MUm plastic-embedded sections stained with toluidine blue, the sarcocyst wall was 2.5-5.2 MUm thick and had branched villar protrusions (vp)-like branches of a dead tree. By SEM, the sarcocyst wall had a mesh-like structure with irregularly shaped vp that were folded over the sarcocyst wall. On each vp there were uniform papillomatous structures that were 100 nm wide. By TEM, vp were up to 6 MUm long and contained filamentous tubular structures, most of which were parallel to the long axis of the projections; granules were absent from these tubules. By TEM, bradyzoites within the same cyst varied from 11.2 to 16.8 MUm in length. By TEM, bradyzoites had a very long (10 MUm) convoluted mitochondrion, up to 12 dense granules, but only 2 rhoptries. This redescription should help to differentiate the sarcocysts of S. fusiformis from similar sarcocysts in domestic and wild ruminants. PMID- 25111677 TI - A superhydrophobic chip based on SU-8 photoresist pillars suspended on a silicon nitride membrane. AB - We developed a new generation of superhydrophobic chips optimized for probing ultrasmall sample quantities by X-ray scattering and fluorescence techniques. The chips are based on thin Si3N4 membranes with a tailored pattern of SU-8 photoresist pillars. Indeed, aqueous solution droplets can be evaporated and concentrated at predefined positions using a non-periodic pillar pattern. We demonstrated quantitatively the deposition and aggregation of gold glyconanoparticles from the evaporation of a nanomolar droplet in a small spot by raster X-ray nanofluorescence. Further, raster nanocrystallography of biological objects such as rod-like tobacco mosaic virus nanoparticles reveals crystalline macro-domain formation composed of highly oriented nanorods. PMID- 25111678 TI - SUMO1 genetic polymorphisms may contribute to the risk of nonsyndromic cleft lip with or without palate: a meta-analysis. AB - OBJECTIVE: We conducted the present meta-analysis to investigate whether single nucleotide polymorphisms (SNPs) in the SUMO1 gene contribute to the risk of nonsyndromic cleft lip with or without palate (NSCL/P). METHOD: The Web of Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 2013), EMBASE (1980-2013), CINAHL (1982-2013), and the Chinese Biomedical Database (CBM) (1982-2013) were searched without language restrictions. Meta analysis was performed with the use of the STATA statistical software. RESULTS: Six studies with a total of 1381 NSCL/P patients and 2054 control subjects were included. Twenty-seven functional polymorphisms in the SUMO1 gene were assessed. Our results indicated that SUMO1 genetic polymorphisms were correlated with an increased risk of NSCL/P. Subgroup analysis by the SNP type indicated that 4 functional polymorphisms (rs12470401 T>C, rs16838917 A>G, rs12470529 A>G, and rs7572505 A>G) in the SUMO1 gene might be strongly correlated with NSCL/P risk. Furthermore, ethnicity-stratified analysis demonstrated that SUMO1 genetic polymorphisms were closely related to an increased risk of NSCL/P among both Asians and Caucasians. CONCLUSION: Our findings provide empirical evidence that SUMO1 genetic polymorphisms might be strongly involved in the etiology of NSCL/P, especially for rs12470401 T>C, rs16838917 A>G, rs12470529 A>G, and rs7572505 A>G polymorphisms. PMID- 25111679 TI - Posterior reversible encephalopathy syndrome: An atypical complication of postpartum wound infection. PMID- 25111680 TI - Fluid removal in acute heart failure: diuretics versus devices. AB - PURPOSE OF REVIEW: Fluid removal and relief of congestion are central to treatment of acute heart failure. Diuretics have been the decongestive mainstay but their known limitations have led to the exploration of alternative strategies. This review compares diuretics with ultrafiltration and examines the recent evidence evaluating their use. RECENT FINDINGS: Relevant recent studies are the Diuretic Optimization Strategies Evaluation trial (of diuretics) and the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (of ultrafiltration). The Diuretic Optimization Strategies Evaluation study evaluated strategies of loop diuretic use during acute heart failure (continuous infusion versus intermittent bolus and high dose versus low dose). After 72 h, there was no significant difference with either comparison for the coprimary end points. Patients treated with a high-dose strategy tended to have greater diuresis and more decongestion compared with low-dose therapy, at the cost of transient changes in renal function. The Cardiorenal Rescue Study in Acute Decompensated Heart Failure study showed that in acute heart failure patients with persistent congestion and worsening renal function, ultrafiltration, as compared with a medical therapy, was associated with similar weight loss but greater increase in serum creatinine and more adverse events. SUMMARY: Decongestion remains a major challenge in acute heart failure. Although recent studies provide useful data to guide practice, the relatively poor outcomes point to the continued need to identify better strategies for safe and effective decongestion. PMID- 25111681 TI - Theoretical explanation of the photoswitchable superhydrophobicity of diarylethene microcrystalline surfaces. AB - Two types of superhydrophobic surfaces which show lotus and petal effects were induced on photochromic diarylethene microcrystalline surfaces by UV and visible light irradiation and temperature control. On the surfaces showing the lotus effect, a low-adhesion superhydrophobic property is attributed to the surface structure being covered with densely standing needle-shaped crystals of the closed-ring isomer. On surfaces showing the petal effect, a high-adhesion superhydrophobic surface consists of fine needle-shaped crystals with high density together with a few rod-shaped crystals, where an invasion phenomenon occurs between these rod-shaped crystals. Furthermore, the different superhydrophobic properties of the surfaces are theoretically explained using multipillar surface models. PMID- 25111683 TI - The value of preoperative medical testing for vitreoretinal surgery. AB - PURPOSE: To determine whether preoperative medical testing reduces the risk of postoperative systemic adverse events after vitreoretinal surgery. METHODS: Retrospective cohort study at a single academic university hospital involving a total of 2,215 patients undergoing vitreoretinal surgery. Medical charts of 2,215 patients who underwent vitreoretinal surgery between January 2002 and November 2011 at Vanderbilt University were reviewed for baseline comorbidities, preoperative testing, type of anesthesia during surgery, and systemic adverse events occurring within 30 days after surgery. Main outcome measures were the association of baseline characteristics and preoperative testing with postoperative systemic adverse events. RESULTS: Approximately a half of patients had electrolyte, renal function, and electrocardiogram evaluation. The most common comorbidities were hypertension (53%), diabetes mellitus (37%), and coronary artery disease (18%). The most common preoperative testing performed was blood glucose (58%). A total of 102 systemic adverse events occurred in 89 of 2,215 patients (4%) within the first 30 days after surgery with the majority (72%) occurring within the first 24 hours. The most common adverse event was bradycardia (34%) followed by desaturation (25%). Patients with a history of coronary artery disease, asthma, chronic renal disease, or receiving general anesthesia had a 2.04 (P = 0.01), 2.18 (P = 0.03), 2.76 (P < 0.01), and 3.72 (P < 0.001) increased odds of developing postoperative systemic adverse events, respectively. Multivariate logistic regression analysis demonstrated no significant correlation between preoperative testing and postoperative adverse events. CONCLUSION: Incidence of postoperative systemic adverse events after vitreoretinal surgery was 4% and was significantly increased in patients with coronary artery disease, asthma, chronic renal disease, or receiving general anesthesia. In this series, preoperative testing did not measurably influence rates of postoperative systemic complications. PMID- 25111682 TI - Expression of receptor activator of nuclear factor kappa-B as a poor prognostic marker in breast cancer. AB - PURPOSE: Receptor activator of nuclear factor kappa-B and its ligand (RANK/RANKL) and Osteoprotegerin (OPG) are key molecules for regulating osteoclastic activity in bone. However, little is known about the role of RANK-related molecules in breast cancer prognosis. We aimed to evaluate RANK, RANKL, and OPG expression and the associated clinical impact in breast cancer. METHODS: Tissue microarray (TMA) from 185 patients with primary breast cancer was established. Immunohistochemistry for RANK, RANKL, and OPG was performed. Clinicopathologic features and survival outcomes associated with expression of RANK, RANKL, and OPG were analyzed. RESULTS: RANK, RANKL, and OPG were expressed in 74.1%, 78.4%, and 45.9% of patients, respectively. RANKL expression was associated with lower Ki-67 level. OPG expression was related to small tumor size, node negativity, and low Ki-67. There was no significant difference in clinicopathologic features between tumors with RANK and those without RANK. RANK expression was significantly associated with poor disease-free survival in univariate analysis (P = 0.04) and multivariate analysis (P = 0.02). RANKL expression was associated with improved skeletal disease-free survival in multivariate analysis (P = 0.03). CONCLUSIONS: The RANK/RANKL pathway regulated by OPG may have a role in predicting progression and prognosis of breast cancer. PMID- 25111684 TI - Diagnostic and Therapeutic Challenges. PMID- 25111685 TI - Malattia leventinese/Doyne honeycomb retinal dystrophy in a chinese family with mutation of the EFEMP1 gene. AB - PURPOSE: To characterize the clinical features and molecular genetic findings in a Chinese pedigree with Malattia leventinese/Doyne honeycomb retinal dystrophy. METHODS: All patients underwent ophthalmologic examinations, including Snellen best-corrected visual acuity, fundus photography, fundus autofluorescence imaging, fundus fluorescein angiography, and optical coherence tomography. Genomic DNA was isolated from blood samples. All exons of EFEMP1 were amplified by polymerase chain reaction and sequenced. Possible structural and functional impacts of the protein because of amino acid substitution were predicted by bioinformatics analysis. RESULTS: A heterozygous missense mutation comprising C > T in exon 10 of EFEMP1 was identified in all patients of the pedigree; this resulted in an amino acid substitution at position 345 (Arg345Trp, R345W). Clinically, six patients from the Chinese family were ascertained with varying degrees of early onset drusen. Besides the drusen, choroidal neovascularization and retinal pigment epithelium changes were noted in some patients. Increased autofluorescence corresponding to the drusen was detected in the R345W mutation patients. Intrafamilial patients with Malattia leventinese/Doyne honeycomb retinal dystrophy seem to be phenotypically variable in visual loss, ophthalmoscopic findings, autofluorescence imaging, and optical coherence tomography changes. The amino acid change may have an effect on protein structure and function through bioinformatics analysis. CONCLUSION: The R345W mutation in EFEMP1 caused Malattia leventinese/Doyne honeycomb retinal dystrophy in a Chinese family. This is the first report, as per our knowledge, of the R345W mutation in EFEMP1 in a Chinese pedigree of this disease. PMID- 25111686 TI - Neuroprotective effects of intravitreal triamcinolone acetonide and dexamethasone implant in rabbit retinas after pars plana vitrectomy and silicone oil injection. AB - PURPOSE: To investigate potential retinal neuroprotective effects of intravitreal triamcinolone acetonide and dexamethasone implant in rabbits after pars plana vitrectomy and intravitreal silicone oil injection. METHODS: The right eyes of 84 rabbits, divided into 3 groups of 28 rabbits each, underwent standard 3-port pars plana vitrectomy with silicone oil (SO group), silicone oil and intravitreal dexamethasone implant (SO/DEX group), or silicone oil and triamcinolone acetonide (SO/TA group). The retina from the left eye of each rabbit served as a control. The animals were killed at 4 weeks after surgery. Qualitative and quantitative histopathologic analyses were performed 4 weeks after surgery, and investigation for apoptosis was performed using the Tunel assay. RESULTS: Intravitreal triamcinolone acetonide and dexamethasone implant were associated with increased retinal neuronal survival, primarily in the outer nuclear layer, inner nuclear layer, and ganglion cell layer. In the SO group, the cell density in eyes that underwent PPV/SO was 31% lower in the outer nuclear layer, 33% lower in the inner nuclear layer, and 45% lower in the ganglion cell layer compared to control eyes (p < 0.05 for all PPV/SO versus control comparisons). Compared to eyes that underwent PPV/SO, the cell density in eyes treated with triamcinolone was 27% higher in the outer nuclear layer, 66% higher in the inner nuclear layer, and 100% higher in the ganglion cell layer (p < 0.05 for all triamcinolone versus PPV/SO comparisons). Compared to eyes that underwent PPV/SO, the cell density in eyes treated with dexamethasone was 46% higher in the outer nuclear layer, 62% higher in the inner nuclear layer, and 77% higher in the ganglion cell layer (p < 0.05 for all dexamethasone versus PPV/SO comparisons). Analyses using the Tunnel assay demonstrated apoptotic bodies in all eyes in the SO group, compared with none of the eyes in the SO/TA and SO/DEX groups. The presence of cell nuclei stained with 49,6-diamidino-2-phenylindole (DAPI) was demonstrated in all groups. CONCLUSION: In this experimental model of neuroprotection, increased retinal neuronal survival was seen in the steroid-treated groups compared with the controls. PMID- 25111687 TI - Posterior scleral reinforcement and vitrectomy for myopic foveoschisis in extreme myopia. AB - PURPOSE: To evaluate the effect of surgical posterior scleral reinforcement in extremely myopic patients (axial length >=30 mm) with myopic foveoschisis. METHODS: The retrospective interventional case series study included patients with an axial length >=30 mm, posterior scleral staphyloma, and myopic foveoschisis, who were treated either by posterior scleral reinforcement and 23 gauge 3-port pars plana vitrectomy (posterior scleral reinforcement group) or by vitrectomy (vitrectomy group) alone. All eyes additionally underwent cataract surgery. RESULTS: The study included 28 patients (28 eyes) with no significant (all P > 0.05) difference between the posterior scleral reinforcement group (n = 14) and the vitrectomy group (n = 14) in age, refractive error, axial length, and preoperative best-corrected visual acuity (BCVA). In addition to posterior scleral staphyloma and foveoschisis, a macular hole, a macular hole-associated retinal detachment, and a macular detachment without macular hole were present in three eyes, five eyes, and one eye, respectively in the study group and in three eyes, three eyes, and six eyes, respectively in the control group. In the study group, BCVA was significantly better after surgery than at baseline (P = 0.005) with an improvement in BCVA in 13 eyes, whereas BCVA was unchanged in 1 eye. In the control group, BCVA at baseline and at the end of follow-up did not differ significantly (P = 0.22). Gain in BCVA was marginally significantly higher in the study group than that in the control group (improvement by 0.69 +/- 0.76 logMAR vs. 0.19 +/- 0.54 logMAR; P = 0.05). The number of eyes with any improvement in BCVA (13 [93%] eyes vs. 11 [79%] eyes; P = 0.289) did not differ between both groups; an improvement in BCVA by more than 2 lines (10 [71%] eyes vs. 3 [21%] eyes; P = 0.009) was significantly higher in the study group than that in the control group. Anatomical success (defined as closure of macular holes and collapse of the foveoschisis) was achieved earlier in the study group (3.7 +/- 3.2 months vs. 6.2 +/- 3.0 months; P = 0.04). CONCLUSION: Posterior scleral reinforcement in association with vitrectomy, as compared with vitrectomy alone, was associated with a higher improvement in visual acuity in extremely myopic eyes with foveoschisis. PMID- 25111688 TI - The cost of being queen: investment across Pogonomyrmex harvester ant gynes that differ in degree of claustrality. AB - The role of the ant colony largely consists of non-reproductive tasks, such as foraging, tending brood, and defense. However, workers are vitally linked to reproduction through their provisioning of sexual offspring, which are produced annually to mate and initiate new colonies. Gynes (future queens) have size associated variation in colony founding strategy (claustrality), with each strategy requiring different energetic investments from their natal colony. We compared the per capita production cost required for semi-claustral, facultative, and claustral gynes across four species of Pogonomyrmex harvester ants. We found that the claustral founding strategy is markedly expensive, costing approximately 70% more energy than that of the semi-claustral strategy. Relative to males, claustral gynes also had the largest differential investment and smallest size variation. We applied these investment costs to a model by Brown and Bonhoeffer (2003) that predicts founding strategy based on investment cost and foraging survivorship. The model predicts that non-claustral foundresses must survive the foraging period with a probability of 30-36% in order for a foraging strategy to be selectively favored. These results highlight the importance of incorporating resource investment at the colony level when investigating the evolution of colony founding strategies in ants. PMID- 25111689 TI - Control of larval and egg development in Aedes aegypti with RNA interference against juvenile hormone acid methyl transferase. AB - RNA interference (RNAi) is a powerful approach for elucidating gene functions in a variety of organisms, including mosquitoes and many other insects. Little has been done, however, to harness this approach in order to control adult and larval mosquitoes. Juvenile hormone (JH) plays a pivotal role in the control of reproduction in adults and metamorphism in larval mosquitoes. This report describes an approach to control Aedes aegypti using RNAi against JH acid methyl transferase (AeaJHAMT), the ultimate enzyme in the biosynthetic pathway of JH III that converts JH acid III (JHA III) into JH III. In female A. aegypti that were injected or fed jmtA dsRNA targeting the AeaJHAMT gene (jmtA) transcript, egg development was inhibited in 50% of the treated females. In mosquito larvae that were fed transgenic Pichia pastoris cells expressing long hair pin (LHP) RNA, adult eclosion was delayed by 3 weeks causing high mortality. Northern blot analyses and qPCR studies show that jmtA dsRNA causes inhibition of jmtA transcript in adults and larvae, which is consistent with the observed inhibition of egg maturation and larval development. Taken together, these results suggest that jmtA LHP RNA expressed in heat inactivated genetically modified P. pastoris cells could be used to control mosquito populations in the marsh. PMID- 25111690 TI - Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes. AB - Non-alcoholic fatty liver disease (NAFLD) is currently one of the most common types of chronic liver injury. Elevated serum uric acid is a strong predictor of the development of fatty liver as well as metabolic syndrome. Here we demonstrate that uric acid induces triglyceride accumulation by SREBP-1c activation via induction of endoplasmic reticulum (ER) stress in hepatocytes. Uric acid-induced ER stress resulted in an increase of glucose-regulated protein (GRP78/94), splicing of the X-box-binding protein-1 (XBP-1), the phosphorylation of protein kinase RNA-like ER kinase (PERK), and eukaryotic translation initiation factor 2alpha (eIF-2alpha) in cultured hepatocytes. Uric acid promoted hepatic lipogenesis through overexpression of the lipogenic enzyme, acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1) via activation of SREBP-1c, which was blocked by probenecid, an organic anion transport blocker in HepG2 cells and primary hepatocytes. A blocker of ER stress, tauroursodeoxycholic acid (TUDCA), and an inhibitor of SREBP-1c, metformin, blocked hepatic fat accumulation, suggesting that uric acid promoted fat synthesis in hepatocytes via ER stress-induced activation of SREBP-1c. Uric acid-induced activation of NADPH oxidase preceded ER stress, which further induced mitochondrial ROS production in hepatocytes. These studies provide new insights into the mechanisms by which uric acid stimulates fat accumulation in the liver. PMID- 25111693 TI - A hydrophobic hole transporting oligothiophene for planar perovskite solar cells with improved stability. AB - An oligothiophene derivative named DR3TBDTT with high hydrophobicity was synthesized and functioned as the hole transporting material without an ion additive. 8.8% of power conversion efficiency was obtained for CH3NH3PbI3-xClx based planar solar cells with improved stability, compared to devices using Li TFSI doped spiro-MeOTAD. PMID- 25111692 TI - Renoprotective effect of red ginseng in gentamicin-induced acute kidney injury. AB - Aminoglycoside-induced nephrotoxicity is one of the prevalent causes of acute kidney injury (AKI). Oxidative stress-mediated apoptosis of renal tubular cells is known to be a major mechanism of renal injury. Red ginseng extract (RGE) has been reported to possess antioxidant and immune-modulatory activities. We investigated the effect of RGE on gentamicin (GM)-induced apoptosis and oxidative stress in cultured renal tubular cells and animal model of GM-induced AKI. GM induced the generation of reactive oxygen species (ROS) with an increase in NADPH oxidase (NOX) activity and mitochondrial oxidation in NRK-52E cells that were ameliorated with RGE. GM-induced apoptosis of NRK-52E cells, which was associated with an increased expression of mitochondrial Bax, cytosolic cytochrome c, and cleaved caspase-9 and -3, along with a decrease in bcl-2 expression, was also blocked by RGE. In an animal model of GM-induced AKI, RGE treatment significantly attenuated renal dysfunction, cell apoptosis, and tubular damage. RGE ameliorated ROS production in rats with GM-induced AKI, as demonstrated by an increase in the reduced form of glutathione in renal cortex and a decrease in urinary excretion of 8-hydroxy-2'-deoxyguanosine. Our results suggest that RGE protects the kidney from GM-induced AKI via the mechanism of modulation of oxidative stress. PMID- 25111694 TI - Highlighting the importance of metabolic risk factors, obesity, and liver steatosis after pediatric liver transplantation. PMID- 25111691 TI - Merkel cell carcinoma expresses vasculogenic mimicry: demonstration in patients and experimental manipulation in xenografts. AB - Merkel cell carcinoma (MCC) is a highly virulent cutaneous neoplasm that, like melanoma, is a frequent cause of patient morbidity and mortality. The cellular mechanisms responsible for the aggressive behavior of MCC remain unknown. Vasculogenic mimicry (VM) is a phenomenon associated with cancer virulence, including in melanoma, whereby anastomosing laminin networks form in association with tumor cells that express certain endothelial genes. To determine whether VM is a factor in MCC, we employed a relevant xenograft model using two independent human MCC lines. Experimentally induced tumors were remarkably similar histologically to patient MCC, and both contained laminin networks associated with vascular endothelial-cadherin (CD144) and vascular endothelial growth factor receptor 1, as well as Nodal expression typical of VM in melanoma. Moreover, two established chemotherapeutic agents utilized for human MCC, etoposide and carboplatin, induced necrosis in xenografts on systemic administration while enriching for laminin networks in apparently resistant viable tumor regions that persisted. These findings for the first time establish VM-like laminin networks as a biomarker in MCC, demonstrate the experimental utility of the MCC xenograft model, and suggest that VM-rich regions of MCC may be refractory to conventional chemotherapeutic agents. PMID- 25111696 TI - Gift-giving and network structure in rural China: utilizing long-term spontaneous gift records. AB - The tradition of keeping written records of gift received during household ceremonies in many countries offers researchers an underutilized means of data collection for social network analysis. This paper first summarizes unique features of the gift record data that circumvent five prevailing sampling and measurement issues in the literature, and we discuss their advantages over existing studies at both the individual level and the dyadic link level using previous data sources. We then document our research project in rural China that implements a multiple wave census-type household survey and a long-term gift record collection. The pattern of gift-giving in major household social events and its recent escalation is analyzed. There are significantly positive correlations between gift network centrality and various forms of informal insurance. Finally, economic inequality and competitive marriage market are among the main demographic and socioeconomic determinants of the observed gift network structure. PMID- 25111698 TI - Validation of a high throughput flow cytometric in vitro micronucleus assay including assessment of metabolic activation in TK6 cells. AB - Genotoxicity is an unacceptable property for new drug candidates and we employ three screening assays during the drug discovery process to identify genotoxicity early and optimize chemical series. One of these methods is the flow cytometric in vitro micronucleus assay for which protocol optimizations have been described recently. Here, we report further validation of the assay in TK6 cells including assessment of metabolic activation. We first optimized assay conditions to allow for testing with and without metabolic activation in parallel in a 96-well plate format. Then, we tested a set of 48 compounds carefully selected to contain known in vivo genotoxins, nongenotoxins and drugs. Avoidance of irrelevant positives, a known issue with mammalian cell-based genotoxicity assays, is important to prevent early deselection of potentially promising compounds. Therefore, we enriched the validation set with compounds that were previously reported to produce irrelevant positive results in mammalian cell-based genotoxicity assays. The resulting dataset was used to set the relevant cut-off values for scoring a compound positive or negative, such that we obtained an optimal balance of high sensitivity (88%) and high specificity (87%). Finally, we tested an additional set of 16 drugs to further probe assay performance and 14 of them were classified correctly. To our knowledge, the present study is the most comprehensive validation of the in vitro flow cytometric micronucleus assay and the first to report parallel assessment with metabolic activation in reasonable throughput. The assay allows for rapidly screening novel compounds for genotoxicity and is therefore well-suited for use in early drug discovery projects. Environ. PMID- 25111695 TI - Involvement of potato (Solanum tuberosum L.) MKK6 in response to potato virus Y. AB - Mitogen-activated protein kinase (MAPK) cascades have crucial roles in the regulation of plant development and in plant responses to stress. Plant recognition of pathogen-associated molecular patterns or pathogen-derived effector proteins has been shown to trigger activation of several MAPKs. This then controls defence responses, including synthesis and/or signalling of defence hormones and activation of defence related genes. The MAPK cascade genes are highly complex and interconnected, and thus the precise signalling mechanisms in specific plant-pathogen interactions are still not known. Here we investigated the MAPK signalling network involved in immune responses of potato (Solanum tuberosum L.) to Potato virus Y, an important potato pathogen worldwide. Sequence analysis was performed to identify the complete MAPK kinase (MKK) family in potato, and to identify those regulated in the hypersensitive resistance response to Potato virus Y infection. Arabidopsis has 10 MKK family members, of which we identified five in potato and tomato (Solanum lycopersicum L.), and eight in Nicotiana benthamiana. Among these, StMKK6 is the most strongly regulated gene in response to Potato virus Y. The salicylic acid treatment revealed that StMKK6 is regulated by the hormone that is in agreement with the salicylic acid-regulated domains found in the StMKK6 promoter. The involvement of StMKK6 in potato defence response was confirmed by localisation studies, where StMKK6 accumulated strongly only in Potato-virus-Y-infected plants, and predominantly in the cell nucleus. Using a yeast two-hybrid method, we identified three StMKK6 targets downstream in the MAPK cascade: StMAPK4_2, StMAPK6 and StMAPK13. These data together provide further insight into the StMKK6 signalling module and its involvement in plant defence. PMID- 25111699 TI - Assembly of polyelectrolyte multilayer films on supported lipid bilayers to induce neural stem/progenitor cell differentiation into functional neurons. AB - The key factors affecting the success of neural engineering using neural stem/progenitor cells (NSPCs) are the neuron quantity, the guidance of neurite outgrowth, and the induction of neurons to form functional synapses at synaptic junctions. Herein, a biomimetic material comprising a supported lipid bilayer (SLB) with adsorbed sequential polyelectrolyte multilayer (PEM) films was fabricated to induce NSPCs to form functional neurons without the need for serum and growth factors in a short-term culture. SLBs are suitable artificial substrates for neural engineering due to their structural similarity to synaptic membranes. In addition, PEM film adsorption provides protection for the SLB as well as the ability to vary the surface properties to evaluate the effects of physical and mechanical signals on NSPC differentiation. Our results revealed that NSPCs were inducible on SLB-PEM films consisting of up to eight alternating layers. In addition, the process outgrowth length, the percentage of differentiated neurons, and the synaptic function were regulated by the number of layers and the surface charge of the outermost layer. The average process outgrowth length was greater than 500 MUm on SLB-PLL/PLGA (n = 7.5) after only 3 days of culture. Moreover, the quantity and quality of the differentiated neurons were obviously enhanced on the SLB-PEM system compared with those on the PEM-only substrates. These results suggest that the PEM films can induce NSPC adhesion and differentiation and that an SLB base may enhance neuron differentiation and trigger the formation of functional synapses. PMID- 25111700 TI - Automated movement correction for dynamic PET/CT images: evaluation with phantom and patient data. AB - Head movement during a dynamic brain PET/CT imaging results in mismatch between CT and dynamic PET images. It can cause artifacts in CT-based attenuation corrected PET images, thus affecting both the qualitative and quantitative aspects of the dynamic PET images and the derived parametric images. In this study, we developed an automated retrospective image-based movement correction (MC) procedure. The MC method first registered the CT image to each dynamic PET frames, then re-reconstructed the PET frames with CT-based attenuation correction, and finally re-aligned all the PET frames to the same position. We evaluated the MC method's performance on the Hoffman phantom and dynamic FDDNP and FDG PET/CT images of patients with neurodegenerative disease or with poor compliance. Dynamic FDDNP PET/CT images (65 min) were obtained from 12 patients and dynamic FDG PET/CT images (60 min) were obtained from 6 patients. Logan analysis with cerebellum as the reference region was used to generate regional distribution volume ratio (DVR) for FDDNP scan before and after MC. For FDG studies, the image derived input function was used to generate parametric image of FDG uptake constant (Ki) before and after MC. Phantom study showed high accuracy of registration between PET and CT and improved PET images after MC. In patient study, head movement was observed in all subjects, especially in late PET frames with an average displacement of 6.92 mm. The z-direction translation (average maximum = 5.32 mm) and x-axis rotation (average maximum = 5.19 degrees) occurred most frequently. Image artifacts were significantly diminished after MC. There were significant differences (P<0.05) in the FDDNP DVR and FDG Ki values in the parietal and temporal regions after MC. In conclusion, MC applied to dynamic brain FDDNP and FDG PET/CT scans could improve the qualitative and quantitative aspects of images of both tracers. PMID- 25111701 TI - Argument structure and the representation of abstract semantics. AB - According to the dual coding theory, differences in the ease of retrieval between concrete and abstract words are related to the exclusive dependence of abstract semantics on linguistic information. Argument structure can be considered a measure of the complexity of the linguistic contexts that accompany a verb. If the retrieval of abstract verbs relies more on the linguistic codes they are associated to, we could expect a larger effect of argument structure for the processing of abstract verbs. In this study, sets of length- and frequency matched verbs including 40 intransitive verbs, 40 transitive verbs taking simple complements, and 40 transitive verbs taking sentential complements were presented in separate lexical and grammatical decision tasks. Half of the verbs were concrete and half were abstract. Similar results were obtained in the two tasks, with significant effects of imageability and transitivity. However, the interaction between these two variables was not significant. These results conflict with hypotheses assuming a stronger reliance of abstract semantics on linguistic codes. In contrast, our data are in line with theories that link the ease of retrieval with availability and robustness of semantic information. PMID- 25111702 TI - Lewis acid mediated tandem reaction of propargylic alcohols to tetrazoles involving C-O- and C-C-bond cleavage reactions and a C-N-bond formation. AB - A novel and direct synthesis of 1-aryl-5-arylvinyl-tetrazoles from easily prepared propargylic alcohols and TMSN3 is developed in the presence of TMSCl under mild conditions (TMS = trimethylsilyl). The process involves an allenylazide intermediate, followed by a C-C-bond cleavage and C-N-bond formation to afford the desired products. Moreover, this method offers a good functional group applicability and can be scaled-up to grams (yield up to 85 %). PMID- 25111703 TI - Perfectionism, neuroticism, and daily stress reactivity and coping effectiveness 6 months and 3 years later. AB - The present study addressed a fundamental gap between research and clinical work by advancing longitudinal explanatory conceptualizations of stress and coping processes that trigger daily affect in the short- and long-term for individuals with higher levels of personality vulnerability. Community adults completed measures of 2 higher order dimensions of perfectionism (personal standards [PS], self-criticism [SC]), neuroticism, and conscientiousness. Then, 6 months later and again 3 years later, participants completed daily questionnaires of stress, coping, and affect for 14 consecutive days. PS was associated with aggregated daily problem-focused coping and positive reinterpretation, whereas SC was uniquely associated with daily negative social interactions, avoidant coping, negative affect, and sadness at Month 6 and Year 3. Multilevel modeling results demonstrated that both individuals with higher PS and those with higher SC were emotionally reactive to event stress, negative social interactions, and avoidant coping at Month 6 and Year 3 and to less perceived control at Year 3. Positive reinterpretation was especially effective for individuals with higher SC at Month 6 and Year 3. The effects of PS on daily stress reactivity and coping (in)effectiveness were clearly distinguished from the effects of neuroticism and conscientiousness, whereas the SC effects were due to shared overlap with PS and neuroticism. The present findings demonstrate the promise of using repeated daily diary methodologies to help therapists and clients reliably predict future client reactions to daily stressors, which, in turn, could help guide interventions to break apart dysfunctional patterns connected to distress and build resilience for vulnerable individuals. PMID- 25111704 TI - Predicting job satisfaction: a new perspective on person-environment fit. AB - There may be 2 ways to look at person-environment (P-E) fit: the extent to which the environment matches the person (which, in the case of person-job [P-J] fit, we term ideal-job actualization) and the extent to which the person matches the environment (which we term actual-job regard; cf. Hardin & Larsen, 2014). Adults employed full time in the United States (n = 251; 49.8% women) completed an online survey that included measures assessing these 2 perspectives on P-J fit, along with measures of job and life satisfaction. Ideal-job actualization and actual-job regard were empirically and conceptually distinct, each accounting for unique variance in overall job satisfaction, even after controlling for overall life satisfaction and remuneration. Looking at fit from these 2 frames of reference may give a more complete perspective that accounts for critical outcomes, like satisfaction, as well as suggest novel approaches to career counseling. PMID- 25111705 TI - Classification challenges in perfectionism. AB - High performance expectations are central to perfectionism, but because most participants endorse high standards, it becomes difficult for practitioners and researchers to accurately screen for perfectionists. We addressed problems linked to the measurement and classification of perfectionism by testing various strategies aimed at broadening the range and skew of scores on the Standards subscale from the Almost Perfect Scale-Revised (APS-R; Slaney, Mobley, Trippi, Ashby, & Johnson, 1996). Randomly assigned participants (N = 506) completed the APS-R following standard instructions or 1 of 2 variations, one prompting participants to consider their responses in light of a normal distribution of scores and another in which participants used a visual analog (slider) scale. The visual analog scale produced more differentiated scores, but range restrictions and skewed distributions remained for all 3 variations. Statistical transformations improved skew. Factor mixture modeling was conducted using transformed and nontransformed perfectionism scores along with criterion indicators of emotion regulation (reappraisal or suppression), perceived stress, and depression. Results supported a 3-class model, although more balanced distributions of classes emerged than were previously reported. Perfectionists were differentiated from nonperfectionists by their higher standards scores. Maladaptive perfectionists scored highest among the classes on most self-critical perfectionism indicators, suppression, perceived stress, and depression. Adaptive perfectionists had the lowest levels of perceived stress and depression and scored highest on reappraisal. Both perfectionist classes had generally comparable concerns about mistakes, but criterion indicators suggested those were more problematic for maladaptive perfectionists. Results supported the value of incorporating adaptive and maladaptive criterion indicators in classification models. PMID- 25111706 TI - Compromises in career-related decisions: examining the role of compromise severity. AB - This study tested L. S. Gottfredson's (1996) revised compromise theory by examining whether the relative importance of job sex type, job prestige, and person-job interest congruence for predicting job choice changed as the level of compromise required changed. The fully within-persons design had participants engage in a simulated occupational choice task where job sex type and job prestige were manipulated to be experimentally independent. Participants 1st categorized jobs as unacceptable, acceptable, or preferred. Then, within each category, they made further pairwise choices among jobs in that category. In Study 1, participants were 168 college seniors (124 women, 44 men) from a large Midwestern university. In Study 2, participants were 262 (146 women, 116 men) individuals residing in the United States and recruited via Amazon's Mechanical Turk platform. Across both studies, job sex type predicted choice when large compromises were required. Across both studies, job prestige did not predict choice when moderate compromises were required. In Study 2 but not Study 1, person-job interest congruence predicted choice when minimal compromises were required. PMID- 25111707 TI - Male Asian international students' perceived racial discrimination, masculine identity, and subjective masculinity stress: a moderated mediation model. AB - This study examined male Asian international college students' perceptions of racial discrimination, subjective masculinity stress, centrality of masculine identity, and psychological distress by testing a moderated mediation model. Participants were 160 male Asian international college students from 2 large public universities. Participants' perceived racial discrimination was positively related to their subjective masculinity stress only at high (but not low) levels of masculine identity centrality. Additionally, subjective masculinity stress was positively related to psychological distress, although this association was stronger among those who reported high levels of masculine identity centrality. The authors also detected a moderated mediation effect in which subjective masculinity stress mediated the relationship between perceived racial discrimination and psychological distress only at high (but not low) levels of masculine identity centrality. These findings contribute to the counseling psychology literature by highlighting the connections between race- and gender related stressors as well as the relevance of masculine identity to an understanding of men's mental health. PMID- 25111709 TI - Sortase-based bio-organic strategies for macromolecular synthesis. AB - Protein ligation sorted: SrtA is one of the molecules nature uses to perform chemoselective ligation on amazingly complex protein molecules. Sortase-mediated ligation (SML) with chemoselective reactions will find a variety of applications in chemistry, biology, and medicine in the near future. PMID- 25111708 TI - Characterization of BPSS1521 (bprD), a regulator of Burkholderia pseudomallei virulence gene expression in the mouse model. AB - The Gram-negative saprophytic bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a severe infectious disease of both humans and animals. Severity of the disease is thought to be dependent on both the health status of the host, including diabetes mellitus and kidney disease, and bacterial derived factors. To identify the bacterial factors important during an acute infection, gene expression profiles in the spleen, lung, and liver of BALB/c (Th2 prototype) and C57BL/6 mice (Th1 prototype) were determined using DNA microarrays. This analysis identified BPSS1521 (bprD), a predicted transcriptional regulator located in the type III secretion system (T3SS-3) operon, to be up regulated, specifically in C57BL/6 mice. BALB/c mice infected with a bprD mutant showed a shorter time to death and increased inflammation, as determined by histopathological analysis and enumeration of bacteria in the spleen. Elevated numbers of multinucleated giant cells (MNGCs), which is the hallmark of melioidosis, were detected in both the wild-type and the bprD mutants; a similar elevation occurs in melioidosis patients. One striking observation was the increased expression of BPSS1520 (bprC), located downstream of bprD, in the bprD mutant. BprC is a regulator of T6SS-1 that is required for the virulence of B. pseudomallei in murine infection models. Deletion of bprD led to the overexpression of bprC and a decreased time to death. bprD expression was elevated in C57BL/6--as compared to BALB/c--mice, suggesting a role for BprD in the natural resistance of C57BL/6 mice to B. pseudomallei. Ultimately, this analysis using mice with different immune backgrounds may enhance our understanding of the outcomes of infection in a variety of models. PMID- 25111711 TI - Fluoroscopic removal of 'lost thread' IUCD's: a novel second line technique. AB - Intrauterine contraceptive devices (IUCDs) with lost threads are an infrequent but growing problem, and there are several successful first-line methods of retrieving the devices. In the event of retrieval failure, we propose a novel second-line technique using an endovascular snare under direct fluoroscopic guidance. A total of 137 women were referred with 'lost string' IUCDs and underwent removal using a snare device, designed for endovascular foreign body retrieval, inserted transcervically. The snare is manipulated to catch the stem of the IUCD under C-arm fluoroscopy. The successful removal rate was 89.6%. The average screening time was 3 min 29 s, with a median air kerma of 12.33 mGy and DAP of 985 mGy cm(2), which was considered minimal and comparable with similar gynaecological interventional procedures. There were no significant complications, with the procedure being tolerated and pain free in 97.8% of cases. PMID- 25111710 TI - Different requirements for GFRalpha2-signaling in three populations of cutaneous sensory neurons. AB - Many primary sensory neurons in mouse dorsal root ganglia (DRG) express one or several GFRalpha's, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFRalpha2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFRalpha2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of glabrous epidermis. However, little is known about this receptor in other Ret-expressing DRG neuron populations. Here we have investigated two populations of Ret-positive low-threshold mechanoreceptors that innervate different types of hair follicles on mouse back skin: the small C-LTMRs and the large Abeta-LTMRs. Using GFRalpha2-KO mice and immunohistochemistry we found that, similar to the nonpeptidergic nociceptors, GFRalpha2 controls the cell size but not the survival of both C-LTMRs and Abeta-LTMRs. In contrast to the nonpeptidergic neurons, GFRalpha2 is not required for the target innervation of C-LTMRs and Abeta-LTMRs in the back skin. These results suggest that different factors drive target innervation in these three populations of neurons. In addition, the observation that the large Ret-positive DRG neurons lack GFRalpha2 immunoreactivity in mature animals suggests that these neurons switch their GFRalpha signaling pathways during postnatal development. PMID- 25111712 TI - Bandgap engineering through nanocrystalline magnetic alloy grafting on reduced graphene oxide. AB - High conductivity and the absence of ferromagnetism in pristine graphene fail to satisfy primary criteria for possible technological application in spintronics. Opening of the bandgap in graphene is primarily desirable for such applications. We report a simplified and novel approach of controlled grafting of a magnetic alloy on reduced graphene oxide. This eventually leads to ferromagnetism of the stable hybrid material at room temperature, with a large moment (~1.2 MUB) and a remarkable decrease in conductivity (~10 times) compared to highly ordered pyrolytic graphite. Our model band-structure calculation indicates that the combined effect of controlled vacancies and impurities attributed to the nanocrystalline alloy grafting leads to a promising step toward band gap engineering. PMID- 25111714 TI - No gain, no pain: NaV1.7 as an analgesic target. AB - Chronic pain is one of the most complex and difficult to manage clinical problems, with the therapeutic utility of current-generation analgesics restricted by problems such as dose-limiting side effects, tolerance, and the potential for addiction. The voltage-gated sodium channel NaV1.7 plays a key role in setting the threshold for action potential generation in primary sensory neurons, and humans that lack this channel are completely insensitive to pain. In this Viewpoint, we examine the potential of NaV1.7 as an analgesic target a well as the challenges involved in developing therapeutically useful subtype-selective inhibitors of this ion channel. PMID- 25111713 TI - Association between noninvasive fibrosis markers and cardio-vascular organ damage among adults with hepatic steatosis. AB - Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD fibrosis score (NFS), is a predictor of cardiovascular mortality in individuals with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e., fibrosis stage) is associated with more pronounced cardiovascular organ damage is unsettled. In this study, we analyzed the clinical utility of NFS in assessing increased carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI). In this cross-sectional study NFS, cIMT and LVMI were assessed in 400 individuals with ultrasonography-diagnosed steatosis. As compared with individuals at low probability of liver fibrosis, individuals both at high and at intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein (hsCRP), fibrinogen, cIMT, and LVMI, and lower insulin-like growth factor-1 (IGF-1) levels. The differences in cIMT and LVMI remained significant after adjustment for smoking and metabolic syndrome. In a logistic regression model adjusted for age, gender, smoking, and diagnosis of metabolic syndrome, individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT>0.9 mm, (OR 3.95, 95% CI 1.12-13.87) as compared with individuals at low probability of fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased risk of left ventricular hypertrophy (LVH) (OR 3.55, 95% CI 1.22-10.34) as compared with individuals at low probability of fibrosis. In conclusion, advanced fibrosis, determined by noninvasive fibrosis markers, is associated with cardiovascular organ damage independent of other known factors. PMID- 25111715 TI - Fetal phenotype associated with the 22q11 deletion. AB - The 22q11 deletion syndrome is one of the most common human microdeletion syndromes, with a wide spectrum of abnormalities. The fetal phenotype associated with the 22q11 deletion is poorly described in the literature. A national retrospective study was performed from 74 feto-pathological examinations. The objectives were to evaluate the circumstances of the 22q11 deletion diagnosis and to describe fetal anomalies. Post mortem examinations were performed after 66 terminations of pregnancy and eight fetal deaths. The series included nine fetuses from the first trimester, 55 from the second trimester, and ten from the third trimester. A 22q11 FISH analysis was recommended for 57 fetuses after multidisciplinary prenatal diagnostic counseling and for 17 fetuses by a fetal pathologist. Conotruncal heart defects were the most common anomalies (65 fetuses), followed by thymus defects (62 fetuses), and malformations of the urinary tract (25 fetuses). This study identified several unusual and severe features rarely described in the literature. Neurological abnormalities were described in ten fetuses, with seven neural tube defects and five arhinencephalies. This series also included lethal malformations: two hypoplastic left heart syndromes, two bilateral renal agenesis, and one tracheal agenesis. Genetic analysis for a 22q11 deletion is usually indicated when a congenital conotruncal heart and/or thymus defect is detected, but might also be useful in case of other lethal or severe malformations that initially led to the termination of pregnancy. PMID- 25111718 TI - [Invitation to the Congress of Visceral Medicine 2014 in Leipzig]. PMID- 25111717 TI - [Prof. Dr. med. Peter Galle]. PMID- 25111716 TI - The ecology of prescription opioid abuse in the USA: geographic variation in patients' use of multiple prescribers ("doctor shopping"). AB - PURPOSE: This study estimates the prevalence in US counties of opioid patients who use large numbers of prescribers, the amounts of opioids they obtain, and the extent to which their prevalence is predicted by ecological attributes of counties, including general medical exposure to opioids. METHODS: Finite mixture models were used to estimate the size of an outlier subpopulation of patients with suspiciously large numbers of prescribers (probable doctor shoppers), using a sample of 146 million opioid prescriptions dispensed during 2008. Ordinary least squares regression models of county-level shopper rates included independent variables measuring ecological attributes of counties, including rates of patients prescribed opioids, socioeconomic characteristics of the resident population, supply of physicians, and measures of healthcare service utilization. RESULTS: The prevalence of shoppers varied widely by county, with rates ranging between 0.6 and 2.5 per 1000 residents. Shopper prevalence was strongly correlated with opioid prescribing for the general population, accounting for 30% of observed county variation in shopper prevalence, after adjusting for physician supply, emergency department visits, in-patient hospital days, poverty rates, percent of county residents living in urban areas, and racial/ethnic composition of resident populations. Approximately 30% of shoppers obtained prescriptions in multiple states. CONCLUSIONS: The correlation between prevalence of doctor shoppers and opioid patients in a county could indicate either that easy access to legitimate medical treatment raises the risk of abuse or that drug abusers take advantage of greater opportunities in places where access is easy. Approaches to preventing excessive use of different prescribers are discussed. PMID- 25111719 TI - Endoscopic management for patients with serrated polyposis syndrome is feasible and effective: a prospective observational study at a tertiary centre. AB - BACKGROUND AND STUDY AIMS: Serrated polyposis syndrome is a rare condition in which multiple serrated lesions develop all over the colon, which is thought to be associated with an increased risk for the development of cancer. The aim of this study was to investigate the feasibility of endoscopic treatment and standardised surveillance in patients with this increasingly recognised syndrome. METHODS: From September 2010 to November 2013, consecutive patients were included in a prospective study. All patients underwent chromoendoscopy at first presentation and during surveillance. Follow-up examinations were carried out at 3 month intervals until complete clearance was achieved. Afterwards, patients entered a standardised surveillance protocol with a chromoendoscopic colonoscopy annually. RESULTS: Altogether 100 colonoscopies were carried out in 28 patients, with endoscopic resection of 436 lesions. Total clearance was accomplished in 27 patients (96.0 %) after 2.5 colonoscopies (range 1 - 8). Histology revealed 359 hyperplastic polyps (82.3 %), 37 sessile serrated adenomas (8.5 %), 36 low-grade adenomas (8.3 %), and one patient with advanced colorectal cancer. Twelve patients (42.8 %) had serrated polyps > 10 mm in size. During the surveillance period, 86 additional lesions were detected and resected. The mean follow-up period was 21.5 months (range 2 - 39 months). No interval carcinoma was detected during the surveillance. CONCLUSIONS: The present study indicates that endoscopic management in patients who meet the diagnostic criteria for serrated polyposis syndrome is feasible and safe. In particular, the incidence of colorectal cancer in this cohort was lower in comparison with previous studies. PMID- 25111720 TI - [Actors in liver transplantation advocate greater transparency and systematic evaluations of transplant centres]. AB - BACKGROUND: Following the introduction of the MELD score, the survival rates have worsened after liver transplantation (LTX) in Germany. Existing organ shortages, shorter survival rates after LTX, and failures in the liver allocation process provide true challenges. Facilitated by a structured questionnaire, the appropriate German liver transplantation actors were approached with regard to these challenges for the first time. The aim was to provide a balanced experts' view in an anonymous fashion thereby identifying areas for potential improvement. METHOD: Data collection was performed by a structured, standardised, anonymous survey of all LTX centres in Germany. RESULTS: We received 75 % replies of the questionnaires, 35 of 36 participants responded to more than 75 % of all questions. The following key points were highlighted. A minimum amount of LTX per centre was deemed important and monetary incentives must not exist. The ultimate goal of LTX is a prolongation of life and social as well as occupational reintegration. Quality management and transparent LTX registers are prerequisites for both adequate organ allocation and distribution of resources in order to achieve the best possible transplant outcomes. CONCLUSION: The German liver transplant experts consider transparency of organ allocation and systematic evaluation of the quality of transplant centres and the transplantation process itself to be mandatory, however, executed in a participatory way. A scoring system to facilitate the decision making process in order to predict the likelihood of satisfactory LTX outcome thereby circumventing some of the ethical and constitutional doubts would be highly appreciated. PMID- 25111721 TI - Invasive cardiac aspergillosis after orthotopic liver transplantation. AB - Invasive aspergillus infection occurs in 5 - 42 % of liver-transplanted recipients and is a dangerous complication, associated with high mortality if untreated. However, the early diagnosis of invasive aspergillosis can be elusive, as clinical signs are unspecific and the pathogenic agent is difficult to demonstrate. We here report about a 58-year-old man with acute liver failure caused by newly diagnosed chronic hepatitis B infection who underwent liver transplantation. The postoperative course was uneventful, and the patient was discharged after 30 days. After 105 days the patient was readmitted because of fever, recurrent chest and abdominal pain. Computed tomography revealed a cardiac lesion; other diagnostic steps including bone-marrow and endomycordial biopsy, virological and microbiological investigations gave no clear findings. To exclude a malignant process, thoracotomy with mass and simultaneous lower left lobe resection were performed. Histopathological findings revealed an invasive perimyocardial aspergillosis. Immediate intravenous therapy with voriconazole and caspofungin was initiated and monitoring of the mass was performed with transesophageal echocardiography and Cardio-MRI. Due to slightly increase of the lesion, medication was switched to posaconazole and caspofungin. Under this dual fungal treatment the lesion regressed and the patient could be discharged after two months in good clinical condition. Frequent Cardio-MRI scan after discharge showed further mass-regression. Therefore antifungal treatment was switched to oral posaconazole mono-therapy. After one year, complete reduction of the mass was achieved and antifungal therapy was discontinued. Recent diagnostic imaging follow-up showed no pathological finding. PMID- 25111722 TI - [Treatment of a subsequently detected, iatrogenic colonic perforation via minimal invasive rendezvous procedure]. AB - Laparoscopic surgery as primary therapeutical option for iatrogenic colonic perforation after colonoscopy can be complemented by intraoparative colonoscopy in order to detect and treat even difficult accessible lesions. Via the presented method minimal invasisve detection and therapy of perforation can be conducted safely and can lead to reduction of morbidity. PMID- 25111723 TI - [Incidence and treatment of chemotherapy-induced nausea and emesis in gastrointestinal cancer]. AB - The incidence of gastrointestinal (GI) cancer is increasing, with approximately 2 million new cases diagnosed worldwide and about 1.2 million patients dying per year. In Europe, about 500 ,000 people per year are newly diagnosed with GI cancer. The most frequent cancer types that undergo chemotherapy include cancer of the oesophagus, stomach, pancreas, biliary tract and colorectum. In the last years, various new agents and combinations have been demonstrated to improve the prognosis of patients with GI cancer. However, with the introduction of new and more effective systemic treatments, the need for supportive treatment has become more complex. There has been significant improvement in the management of nausea and vomiting arising from highly and moderately emetogenic chemotherapy. Nevertheless, vomiting and especially nausea continue to be two of the most distressing side effects of antineoplastic treatment. For the prevention of chemotherapy-induced nausea and vomiting in highly emetogenic therapy, a triple therapy including a 5-HT3-receptor antagonist (RA), dexamethasone and an NK1-RA, aprepitant or fosaprepitant are recommended. In moderately emetogenic regimens, updated guidelines recommend the combination of the second-generation 5-HT3-RA palonosetron with dexamethasone, providing improved protection against acute nausea and vomiting, and demonstrating superior prevention in the delayed phase. This review provides an update of the revised clinical guidelines for antiemetic treatment and prophylaxis in GI cancer patients receiving chemotherapy. PMID- 25111724 TI - [Differential diagnosis of diarrhoea]. AB - Diarrhoea is a common symptom and numerous differential diagnoses must be considered. This article illustrates approaches for a rational and efficient work up based on practical facilities in acute diarrhoea and fostered by 4 key questions scrutinising chronic diarrhoea. The applications of imaging methods (endoscopy, ultrasonography) are discussed along with infectious topics and function testing. The aim of this contribution is to help patients to get a precise diagnosis in a most rational way. This implies a transparent and targeted medical strategy, avoiding selective intuitions ("trial and error") as well as extensive diagnostic overdoing in the case of only putative diarrhoea. Knowing the potential of diagnostic methods which are (or can) possibly not performed regularly in the physician's office, and their requirements/limitations is an important component in this situation. The basic fundament for application of such methods, however, and the clue to economic diagnosis as well as the differential diagnosis of diarrhoeal diseases are the history and simple tests. PMID- 25111725 TI - [Endoscopic or surgical cystogastrostomy for pancreatic pseudocysts: finally a clear answer to an old question?]. PMID- 25111726 TI - Twinship as a resource: zygosity- and gender-based comparison of twins' attitudes toward twinship. AB - Aiming to perform the first sociological survey of Hungarian twins, our main question was whether being a twin has positive consequences on one's life. Adult twins completed our questionnaire at three Hungarian summer twin festivals, in hospitals during medical twin studies, and on some websites online. Data represent 140 twin pairs (mean age: 38.2 +/- 14.6 years). We employed some indices for measuring the resource nature of twinship. Three main types of benefits were distinguished: profit of attraction, as 'material capital'; the easier obtainability of cultural goods when twins take part in it, as 'cultural capital'; and positive aspects of an a priori existing dyadic relation, as 'relational capital'. We were interested in the difference among types of twins regarding advantages. We paid special attention to the five groups of twins derived from gender and zygosity (i.e., monozygotic females, monozygotic males, dizygotic females, dizygotic males, opposite-sex pairs). Our analysis showed that Hungarian twins involved in our research basically enjoy their twinship; during their lives they used and still make use of different benefits given by it. In our twin samples, women had more advantages from being a twin than men. Significant differences could be observed on all indicators between monozygotic and dizygotic twins. PMID- 25111729 TI - SurfKin: an ab initio kinetic code for modeling surface reactions. AB - In this article, we describe a C/C++ program called SurfKin (Surface Kinetics) to construct microkinetic mechanisms for modeling gas-surface reactions. Thermodynamic properties of reaction species are estimated based on density functional theory calculations and statistical mechanics. Rate constants for elementary steps (including adsorption, desorption, and chemical reactions on surfaces) are calculated using the classical collision theory and transition state theory. Methane decomposition and water-gas shift reaction on Ni(111) surface were chosen as test cases to validate the code implementations. The good agreement with literature data suggests this is a powerful tool to facilitate the analysis of complex reactions on surfaces, and thus it helps to effectively construct detailed microkinetic mechanisms for such surface reactions. SurfKin also opens a possibility for designing nanoscale model catalysts. PMID- 25111727 TI - Complications associated with the pedicled nasoseptal flap for skull base reconstruction. AB - OBJECTIVES/HYPOTHESIS: To analyze complications associated with nasoseptal flap elevation and reconstruction in endoscopic skull base surgery. STUDY DESIGN: Case series. METHODS: Retrospective chart review of all patients who underwent nasoseptal flap procedure in our institution between 2008 and 2013. RESULTS: A total of 121 patients were identified with a mean follow-up time of 10.4 months. Complications associated with this procedure occurred in 33 patients (27%). The majority of complications were related to the septal donor site and included septal perforation, cartilage necrosis, and prolonged crusting. Other complications included intraoperative injury to the flap pedicle (n = 4) or recurrent/persistent cerebrospinal fluid leak occurring in the early postoperative period (n = 7). Long-term quality-of-life data assessed via Sinonasal Outcome Test-22 questionnaires did not reveal notable differences when compared to preoperative scores. CONCLUSION: The complication rate associated with nasoseptal flap elevation and inset is higher than previously described. The majority of complications became manifest beyond the immediate postoperative period and were associated with the septal donor site, including septal perforation, prolonged crusting, and cartilage necrosis. We hypothesize that donor site morbidity may be related to compromise of the contralateral septal vascular supply during the procedure. The range and frequency of complications of nasal septal flap surgery should be considered in counseling patients who may receive a nasoseptal flap for skull base reconstruction. PMID- 25111731 TI - Measurement of T1 relaxation time of osteochondral specimens using VFA-SWIFT. AB - PURPOSE: To evaluate the feasibility of SWIFT with variable flip angle (VFA) for measurement of T1 relaxation time in Gd-agarose-phantoms and osteochondral specimens, including regions of very short T2 *, and compare with T1 measured using standard methods METHODS: T1 s of agarose phantoms with variable concentration of Gd-DTPA2- and nine pairs of native and trypsin-treated bovine cartilage-bone specimens were measured. For specimens, VFA-SWIFT, inversion recovery (IR) fast spin echo (FSE) and saturation recovery FSE were used. For phantoms, additionally spectroscopic IR was used. Differences and agreement between the methods were assessed using nonparametric Wilcoxon and Kruskal-Wallis tests and intraclass correlation. RESULTS: The different T1 mapping methods agreed well in the phantoms. VFA-SWIFT allowed reliable measurement of T1 in the osteochondral specimens, including regions where FSE-based methods failed. The T1 s measured by VFA-SWIFT were shifted toward shorter values in specimens. However, the measurements correlated significantly (highest correlation VFA-SWIFT versus FSE was r = 0.966). SNR efficiency was generally highest for SWIFT, especially in the subchondral bone. CONCLUSION: Feasibility of measuring T1 relaxation time using VFA-SWIFT in osteochondral specimens and phantoms was demonstrated. A shift toward shorter T1 s was observed for VFA-SWIFT in specimens, reflecting the higher sensitivity of SWIFT to short T2 * spins. Magn Reson Med 74:175-184, 2015. (c) 2014 Wiley Periodicals, Inc. PMID- 25111732 TI - Tracking the actions and possessions of agents. AB - We propose that there is a powerful human disposition to track the actions and possessions of agents. In two experiments, 3-year-olds and adults viewed sets of objects, learned a new fact about one of the objects in each set (either that it belonged to the participant, or that it possessed a particular label), and were queried about either the taught fact or an unrelated dimension (preference) immediately after a spatiotemporal transformation, and after a delay. Adults uniformly tracked object identity under all conditions, whereas children tracked identity more when taught ownership versus labeling information, and only regarding the taught fact (not the unrelated dimension). These findings suggest that the special attention that children and adults pay to agents readily extends to include inanimate objects. That young children track an object's history, despite their reliance on surface features on many cognitive tasks, suggests that unobservable historical features are foundational in human cognition. PMID- 25111733 TI - Development of an applicator for eye lens dosimetry during radiotherapy. AB - OBJECTIVE: To develop an applicator for in vivo measurements of lens dose during radiotherapy. METHODS: A contact lens-shaped applicator made of acrylic was developed for in vivo measurements of lens dose. This lens applicator allows the insertion of commercially available metal oxide semiconductor field effect transistors (MOSFETs) dosemeters. CT images of an anthropomorphic phantom with and without the applicator were acquired. Ten volumetric modulated arc therapy plans each for the brain and the head and neck cancer were generated and delivered to an anthropomorphic phantom. The differences between the measured and the calculated doses at the lens applicator, as well as the differences between the measured and the calculated doses at the surface of the eyelid were acquired. RESULTS: The average difference between the measured and the calculated doses with the applicator was 3.1 +/- 1.8 cGy with a micro MOSFET and 2.8 +/- 1.3 cGy with a standard MOSFET. The average difference without the lens applicator was 4.8 +/- 5.2 cGy with the micro MOSFET and 5.7 +/- 6.5 cGy with the standard MOSFET. The maximum difference with the micro MOSFET was 10.5 cGy with the applicator and 21.1 cGy without the applicator. For the standard MOSFET, it was 6.8 cGy with the applicator and 27.6 cGy without the applicator. CONCLUSION: The lens applicator allowed reduction of the differences between the calculated and the measured doses during in vivo measurement for the lens compared with in vivo measurement at the surface of the eyelid. ADVANCES IN KNOWLEDGE: By using an applicator for in vivo dosimetry of the eye lens, it was possible to reduce the measurement uncertainty. PMID- 25111734 TI - AGR2, an endoplasmic reticulum protein, is secreted into the gastrointestinal mucus. AB - The MUC2 mucin is the major constituent of the two mucus layers in colon. Mice lacking the disulfide isomerase-like protein Agr2 have been shown to be more susceptible to colon inflammation. The Agr2(-/-) mice have less filled goblet cells and were now shown to have a poorly developed inner colon mucus layer. We could not show AGR2 covalently bound to recombinant MUC2 N- and C-termini as have previously been suggested. We found relatively high concentrations of Agr2 in secreted mucus throughout the murine gastrointestinal tract, suggesting that Agr2 may play extracellular roles. In tissue culture (CHO-K1) cells, AGR2 is normally not secreted. Replacement of the single Cys in AGR2 with Ser (C81S) allowed secretion, suggesting that modification of this Cys might provide a mechanism for circumventing the KTEL endoplasmic reticulum retention signal. In conclusion, these results suggest that AGR2 has both intracellular and extracellular effects in the intestine. PMID- 25111735 TI - Generation of rat-induced pluripotent stem cells from a new model of metabolic syndrome. AB - We recently characterized DahlS.Z-Leprfa/Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive rats and Zucker rats, as a new animal model of metabolic syndrome (MetS). Although the phenotype of DS/obese rats is similar to that of humans with MetS, the pathophysiological and metabolic characteristics in each cell type remain to be clarified. Hence, the establishment of induced pluripotent stem cells (iPSCs) derived from MetS rats is essential for investigations of MetS in vitro. Reports of rat iPSCs (riPSCs), however, are few because of the difficulty of comparing to other rodents such as mouse. Recently, the advantage of using mesenchymal stromal cells (MSCs) as a cell source for generating iPSCs was described. We aimed to establish riPSCs from MSCs in adipose tissues of both DS/obese rats and their lean littermates, DahlS.Z-Lepr+/Lepr+ (DS/lean) rats using lentivirus vectors with only three factors Oct4, Klf4, and Sox2 without c-Myc. The morphology, gene expression profiles, and protein expression of established colonies showed embryonic stem cell (ESCs)-like properties, and the differentiation potential into cells from all three germ layers both in vitro and in vivo (teratomas). Both riPSCs became adipocytes after induction of adipogenesis by insulin, T3, and dexamethasone. Real-time PCR analysis also revealed that both riPSCs and the adipose tissue from DS/obese and DS/lean rats possess similar expression patterns of adipocyte differentiation related genes. We succeeded in generating riPSCs effectively from MSCs of both DS/obese and DS/lean rats. These riPSCs may well serve as highly effective tools for the investigation of MetS pathophysiology in vitro. PMID- 25111736 TI - Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone. AB - BACKGROUND: Abiraterone acetate (AA), oral CYP17 inhibitor, is an active agent in the treatment of metastatic castrate-resistant prostate cancer (mCRPC). METHODS: We (R.L.A and N.A) retrospectively evaluated outcome in 12 men who were re treated with AA following prior treatment with AA at the Princess Margaret Cancer Centre. RESULTS: All men were heavily pre-treated for mCRPC with a median of four prior lines of therapy, one of which was AA (given either pre- or post chemotherapy). Eleven out of 12 (92%) men stopped their first treatment course of AA due to progression and one stopped for financial reasons. Seven men had a PSA decrease >=50% following their first AA treatment, of which three (46%) had a PSA decrease >=50% to AA re-treatment. The responses to AA re-treatment were generally short-lived with a median biochemical progression-free survival of 2.3 months and median treatment duration of 3.2 months. No PSA responses to AA re treatment were seen in five men who did not have an initial PSA response to AA. CONCLUSIONS: Our data suggest that AA re-challenge may have limited benefit in select men with mCRPC, and warrants further formal research. PMID- 25111737 TI - Phosphorus reclamation through hydrothermal carbonization of animal manures. AB - Projected shortages of global phosphate have prompted investigation of methods that could be employed to capture and recycle phosphate, rather than continue to allow the resource to be essentially irreversibly lost through dilution in surface waters. Hydrothermal carbonization of animal manures from large farms was investigated as a scenario for the reclamation of phosphate for agricultural use and mitigation of the negative environmental impact of phosphate pollution. Hydrothermal reaction conditions were identified for poultry, swine, and cattle manures that resulted in hydrochar yields of 50-60% for all three manures, and >90% of the total phosphorus present in these systems was contained in the hydrochars as precipitated phosphate salts. Phosphate recovery was achieved in yields of 80-90% by subsequent acid treatment of the hydrochars, addition of base to acid extracts to achieve a pH of 9, and filtration of principally calcium phosphate. Phosphate recovery was achieved in yields of 81-87% based on starting manures by subsequent acid treatment of the hydrochars, addition of base to acid extracts to achieve a pH of 9, and filtration of principally calcium phosphate. Swine and cattle manures produced hydrochars with combustion energy contents comparable to those of high-end sub-bituminous coals. PMID- 25111738 TI - Phosphatidic acid in neuronal development: a node for membrane and cytoskeleton rearrangements. AB - Phosphatidic acid (PA) is the simplest phospholipid naturally existing in all living organisms. It constitutes only a minor fraction of the total cell lipids but has attracted considerable attention being both a lipid second messenger and a modulator of membrane shape. The pleiotropic functions of PA are the direct consequence of its very simple chemical structure consisting of only two acyl chains linked by ester bonds to two adjacent hydroxyl groups of glycerol, whose remaining hydroxyl group is esterified with a phosphomonoester group. Hence the small phosphate head group of PA gives it the shape of a cone providing flexibility and negative curvatures in the context of a lipid bilayer. In addition, the negatively charged phosphomonoester headgroup of PA is unique because it can potentially carry one or two negative charges playing a role in the recruitment of positively charged molecules to biomembranes. In consequence, PA has been proposed to play various key cellular functions. In the brain, a fine balance between cell growth, migration and differentiation, and cell death is required to sculpt the nervous system during development. In this review, we will summarize the various functions that have been proposed for PA in neuronal development. PMID- 25111739 TI - The role of functional form in causal-based categorization. AB - Two experiments tested how the functional form of the causal relations that link features of categories affects category-based inferences. Whereas independent causes can each bring about an effect by themselves, conjunctive causes all need to be present for an effect to occur. The causal model view of category representations is extended to include a representation of conjunctive causes and then predictions are derived for 3 category-based judgments: classification, conditional feature predictions, and feature likelihoods. Experiment 1 revealed that subjects' judgments on all 3 tasks were not only sensitive to whether causes were independent or conjunctive but also conformed to the causal model predictions, albeit with an important exception. Experiment 2 revealed that inferences with independent and conjunctive causes were affected quite differently by a manipulation of the strengths of the causal relations (and in the manner predicted by the model). This is the 1st study to show how a single representation of a category's causal knowledge can account for 3 category-based judgments with the same model parameters. Other models of causal-based categories are unable to account for the observed effects. PMID- 25111740 TI - Spotted fever from Rickettsia typhi in an older woman: a case report from a geographic area where it would not be expected. AB - We describe the case of a 75-year-old woman presenting with spotted fever followed by acute renal failure and septic shock. The infection was caused by Rickettsia typhi, not reported in Calabria district (southern Italy) since World War II. The diagnosis of murine typhus was made 3 days after admission and was based solely on clinical criteria when her worsening condition required a prompt move to the intensive care unit. Therapy with tigecycline was then started immediately and the patient improved dramatically. The diagnosis of murine typhus was confirmed 10 days after admission by immunofluorescence assay. Our case is an example of how the diagnosis of murine typhus is challenging. However, in the case of a disease lacking specific symptoms, clinicians should never forget that, even in geographic areas considered free of flea-borne diseases, the components of the enzootic cycle are present and the diagnosis should never be underestimated. PMID- 25111742 TI - Unique mechanism of facile polymorphic conversion of acetaminophen in aqueous medium. AB - Rapid polymorphic conversion of acetaminophen (APAP) in solution, from metastable orthorhombic Form II to the stable monoclinic Form I, is well-known. The mechanism is believed to be solution-mediated phase transformation (SMPT), but with little experimental evidence. The present study was undertaken to understand this phenomenon from both thermodynamic and kinetic perspectives. Reliable apparent solubility of Form II was measured, for the first time, in 0.15 M aqueous NaCl solution at 37 degrees C. The solubility ratio of Form II over Form I, 1.27 +/- 0.04, is quite low, which translates to a relatively low thermodynamic driving force for the conversion. Further solution crystallization experiments at supersaturation levels equal to or much greater than Form II solubility did not result in any crystallization in 10 days. Therefore, fast conversion is not possible through SMPT. To explore alternative mechanisms, molecular dynamics (MD) simulations were conducted to investigate the molecular level dissolution behavior and the solid state differences between the two polymorphs. The MD simulations reveal very different behavior. Form II exhibits a much higher rate of H-bond breakage, leading to the accumulation of a large number of disordered APAP molecules on the crystal surface. This thick disordered molecular layer provides a high local acetaminophen concentration which could be responsible for the fast crystallization of Form I. This was further supported by the observations made, using polarized light microscopy and powder X-ray diffractometry, when monitoring Form II crystals coming into contact with NaCl solution. We thus concluded that the hydrated surface layer is the "catalyst" for the facile phase conversion. This new mechanism, termed as SurFPT (surface facilitated phase transformation), is much more effective in promoting polymorphic transformation than the well-known SMPT. PMID- 25111741 TI - Association between early temperament and depression at 18 years. AB - BACKGROUND: Early childhood temperament, particularly negative emotionality (high tendency to show distress), may be a risk factor for subsequent depression. METHODS: Using data from a large UK cohort (Avon Longitudinal Study of Parents and Children), we examined the association between temperament on the Emotionality Activity Sociability Questionnaire at age 6 and ICD-10 depression at 18. Results were adjusted for a range of confounders. RESULTS: Children with high emotionality scores at age 6 had a 20% (7-36%) increase in the odds of being diagnosed with depression at age 18. CONCLUSIONS: Depression at 18 years has an early developmental diathesis, which means we may be able to identify children at risk of developing depression in young adulthood. PMID- 25111743 TI - Iron concentration increases after moderate endurance exercise: implications for screening of blood transfusion in sports. PMID- 25111744 TI - Assessment of the neurotoxic potential of exposure to 50Hz extremely low frequency electromagnetic fields (ELF-EMF) in naive and chemically stressed PC12 cells. AB - Increasing exposure to extremely low frequency electromagnetic fields (ELF-EMF), generated by power lines and electric appliances, raises concern about potential adverse health effects of ELF-EMF. The central nervous system is expected to be particularly vulnerable to ELF-EMF as its function strongly depends on electrical excitability. We therefore investigated effects of acute (30min) and sub-chronic (48h) exposure to 50Hz ELF-EMF on naive and chemically stressed pheochromocytoma (PC12) cells. The latter have higher levels of iron and/or reactive oxygen species (ROS) and display increased vulnerability to environmental insults. Effects of ELF-EMF on Ca(2+)-homeostasis, ROS production and membrane integrity were assessed using Fura-2 single cell fluorescence microscopy, H2-DCFDA and CFDA assays, respectively. Our data demonstrate that acute exposure of naive PC12 cells to 50Hz ELF-EMF up to 1000MUT fails to affect basal or depolarization evoked [Ca(2+)]i. Moreover, sub-chronic ELF-EMF exposure up to 1000MUT has no consistent effects on Ca(2+)-homeostasis in naive PC12 cells and does not affect ROS production and membrane integrity. Notably, in chemically stressed PC12 cells both acute and sub-chronic ELF-EMF exposure also failed to exert consistent effects on Ca(2+)-homeostasis, ROS production and membrane integrity. Our combined findings thus indicate that exposure to 50Hz ELF-EMF up to 1000MUT, i.e. 10,000 times above background exposure, does not induce neurotoxic effects in vitro, neither in naive nor in chemically stressed PC12 cells. Though our data require confirmation, e.g. in developing neuronal cells in vitro or (developing) animals, it appears that the neurotoxic risk of ELF-EMF exposure is limited. PMID- 25111745 TI - Treatment of latent tuberculosis infection: a network meta-analysis. AB - BACKGROUND: Effective treatment of latent tuberculosis infection (LTBI) is an important component of TB elimination programs. Promising new regimens that may be more effective are being introduced. Because few regimens can be directly compared, network meta-analyses, which allow indirect comparisons to be made, strengthen conclusions. PURPOSE: To determine the most efficacious regimen for preventing active TB with the lowest likelihood of adverse events to inform LTBI treatment policies. DATA SOURCES: PubMed, EMBASE, and Web of Science up to 29 January 2014; clinical trial registries; and conference abstracts. STUDY SELECTION: Randomized, controlled trials that evaluated LTBI treatment in humans and recorded at least 1 of 2 prespecified end points (preventing active TB or hepatotoxicity), without language or date restrictions. DATA EXTRACTION: Data from eligible studies were independently extracted by 2 investigators according to a standard protocol. DATA SYNTHESIS: Of the 1516 articles identified, 53 studies met the inclusion criteria. Data on 15 regimens were available; of 105 possible comparisons, 42 (40%) were compared directly. Compared with placebo, isoniazid for 6 months (odds ratio [OR], 0.64 [95% credible interval {CrI}, 0.48 to 0.83]) or 12 months or longer (OR, 0.52 [CrI, 0.41 to 0.66]), rifampicin for 3 to 4 months (OR, 0.41 [CrI, 0.18 to 0.86]), and rifampicin-isoniazid regimens for 3 to 4 months (OR, 0.52 [CrI, 0.34 to 0.79]) were efficacious within the network. LIMITATIONS: The risk of bias was unclear for many studies across various domains. Evidence was sparse for some comparisons, particularly hepatotoxicity. CONCLUSION: Comparison of different LTBI treatment regimens showed that various therapies containing rifamycins for 3 months or more were efficacious at preventing active TB, potentially more so than isoniazid alone. Regimens containing rifamycins may be effective alternatives to isoniazid monotherapy. PRIMARY FUNDING SOURCE: None. PMID- 25111746 TI - Ene-hydrazide from enol triflate for the regioselective Fischer indole synthesis. AB - Ene-hydrazide prepared from enol triflate undergoes a Fischer indolization reaction to give the corresponding indole with complete regioselectivity. The starting enol triflate is readily accessed in regiochemically defined form from the ketone precursor via various well-established methods. This new protocol was successfully applied to the synthesis of desbromoarborescidine A, a natural beta carboline alkaloid, difficult to prepare with conventional Fischer indole synthesis. PMID- 25111747 TI - Excess body weight affects HbA1c progression irrespective of baseline HbA1c levels in Japanese individuals: a longitudinal retrospective study. AB - PURPOSE/AIM: Obese individuals with normal HbA1c levels and low-body-weight individuals with high-normal HbA1c levels are frequently encountered in clinical settings, but the effects of these phenotypes on the onset of diabetes are poorly understood. Therefore, we addressed this issue in a longitudinal study. MATERIALS AND METHODS: We analyzed clinical parameters, including body mass index (BMI) and HbA1c levels, in 5325 non-diabetic Japanese people aged 20-75 years who underwent four medical checkups between 1999 (baseline) and 2007. The subjects were then classified into six baseline BMI categories, each of which was divided into two HbA1c groups, resulting in a total of 12 groups. RESULTS: In 405 obese subjects with a normal baseline HbA1c (BMI >= 27.0 kg/m(2), HbA1c 5.2-5.6%), the mean HbA1c level increased during the study period, and 50.9% developed prediabetes/diabetes. In contrast, in 77 low-body-weight subjects with a high normal baseline HbA1c (BMI <= 18.9 kg/m(2), HbA1c 5.7-6.4%), the mean HbA1c level remained constant. Similar changes occurred in the other groups during the study, resulting in a linear increase in HbA1c levels with increasing BMI. CONCLUSION: Our results suggest that approximately half of the obese individuals with HbA1c in the normal range develop prediabetes or diabetes within 8 years, whereas low body-weight individuals with high-normal HbA1c are less likely to exhibit worsening in glycemia. Thus, excess body weight may be the primary therapeutic target to prevent the early onset of diabetes, regardless of the individual's HbA1c. PMID- 25111748 TI - Infrared spectroscopic studies on the V-ATPase. AB - V-ATPase is an ATP-driven rotary motor that vectorially transports ions. Together with F-ATPase, a homologous protein, several models on the ion transport have been proposed, but their molecular mechanisms are yet unknown. V-ATPase from Enterococcus hirae forms a large supramolecular protein complex (total molecular weight: ~700,000) and physiologically transports Na+ and Li+ across a hydrophobic lipid bilayer. Stabilization of these cations in the binding site has been discussed on the basis of X-ray crystal structures of a membrane-embedded domain, the K-ring (Na+ and Li+ bound forms). Sodium or lithium ion binding-induced difference FTIR spectra of the intact E. hirae V-ATPase have been measured in aqueous solution at physiological temperature. The results suggest that sodium or lithium ion binding induces the deprotonation of Glu139, a hydrogen-bonding change in the tyrosine residue and rigid alpha-helical structures. Identical difference FTIR spectra between the entire V-ATPase complex and K-ring strongly suggest that protein interaction with the I subunit does not cause large structural changes in the K-ring. This result supports the previously proposed Na+ transport mechanism by V-ATPase stating that a flip-flop movement of a carboxylate group of Glu139 without large conformational changes in the K-ring accelerates the replacement of a Na+ ion in the binding site. This article is part of a Special Issue entitled: Vibrational spectroscopies and bioenergetic systems. PMID- 25111749 TI - Characterisation of the LH2 spectral variants produced by the photosynthetic purple sulphur bacterium Allochromatium vinosum. AB - This study systematically investigated the different types of LH2 produced by Allochromatium (Alc.) vinosum, a photosynthetic purple sulphur bacterium, in response to variations in growth conditions. Three different spectral forms of LH2 were isolated and purified, the B800-820, B800-840 and B800-850 LH2 types, all of which exhibit an unusual split 800 peak in their low temperature absorption spectra. However, it is likely that more forms are also present. Relatively more B800-820 and B800-840 are produced under low light conditions, while relatively more B800-850 is produced under high light conditions. Polypeptide compositions of the three different LH2 types were determined by a combination of HPLC and TOF/MS. The B800-820, B800-840 and B800-850 LH2 types all have a heterogeneous polypeptide composition, containing multiple types of both alpha and beta polypeptides, and differ in their precise polypeptide composition. They all have a mixed carotenoid composition, containing carotenoids of the spirilloxanthin series. In all cases the most abundant carotenoid is rhodopin; however, there is a shift towards carotenoids with a higher conjugation number in LH2 complexes produced under low light conditions. CD spectroscopy, together with the polypeptide analysis, demonstrates that these Alc. vinosum LH2 complexes are more closely related to the LH2 complex from Phs. molischianum than they are to the LH2 complexes from Rps. acidophila. PMID- 25111750 TI - Connection between the membrane electron transport system and Hyn hydrogenase in the purple sulfur bacterium, Thiocapsa roseopersicina BBS. AB - Thiocapsa. roseopersicina BBS has four active [NiFe] hydrogenases, providing an excellent opportunity to examine their metabolic linkages to the cellular redox processes. Hyn is a periplasmic membrane-associated hydrogenase harboring two additional electron transfer subunits: Isp1 is a transmembrane protein, while Isp2 is located on the cytoplasmic side of the membrane. In this work, the connection of HynSL to various electron transport pathways is studied. During photoautotrophic growth, electrons, generated from the oxidation of thiosulfate and sulfur, are donated to the photosynthetic electron transport chain via cytochromes. Electrons formed from thiosulfate and sulfur oxidation might also be also used for Hyn-dependent hydrogen evolution which was shown to be light and proton motive force driven. Hyn-linked hydrogen uptake can be promoted by both sulfur and nitrate. The electron flow from/to HynSL requires the presence of Isp2 in both directions. Hydrogenase-linked sulfur reduction could be inhibited by a QB site competitive inhibitor, terbutryne, suggesting a redox coupling between the Hyn hydrogenase and the photosynthetic electron transport chain. Based on these findings, redox linkages of Hyn hydrogenase are modeled. PMID- 25111751 TI - Vegetating nodules following erosions on the oral cavity: a quiz. Iatrogenic Kaposi's sarcoma associated with pemphigus vulgaris. PMID- 25111752 TI - Prussian blues as a cathode material for lithium ion batteries. AB - Prussian blues (or iron cyanides) and their analogues are attractive in both fundamental studies and industrial applications owing to their chemical and structural diversity. The large open space in their framework provides tunnels and space for the transport and storage of lithium ions. Two Prussian blues were synthesized by a co-precipitation method. The nanosized Fe4 [Fe(CN)6 ]3 and cubic FeFe(CN)6 deliver reversible capacities of 95 mAh g(-1) and 138 mAh g(-1) , respectively. In comparison, FeFe(CN)6 shows cycling and rate performances superior to Fe4 [Fe(CN)6 ]3 . PMID- 25111753 TI - Horizontal transmission of a parasite is influenced by infected host phenotype and density. AB - Transmission is a key determinant of parasite fitness, and understanding the dynamics of transmission is fundamental to the ecology and evolution of host parasite interactions. Successful transmission is often reliant on contact between infected individuals and susceptible hosts. The social insects consist of aggregated groups of genetically similar hosts, making them particularly vulnerable to parasite transmission. Here we investigate how the ratio of infected to susceptible individuals impacts parasite transmission, using the honey bee, Apis mellifera and its microsporidian parasite Nosema ceranae. We used 2 types of infected hosts found simultaneously in colonies; sterile female workers and sexual males. We found a higher ratio of infected to susceptible individuals in groups resulted in a greater proportion of susceptibles becoming infected, but this effect was non-linear and interestingly, the ratio also affected the spore production of infected individuals. The transmission level was much greater in an experiment where the infected individuals were drones than in an experiment where they were workers, suggesting drones may act as intracolonial 'superspreaders'. Understanding the subtleties of transmission and how it is influenced by the phenotype of the infected/susceptible individuals is important for understanding pathogen transmission at population level, and for optimum targeting of parasite control strategies. PMID- 25111754 TI - One third of dynamic protein expression profiles can be predicted by a simple rate equation. AB - Cells respond to environmental stimuli with expression changes at both the mRNA and protein level, and a plethora of known and unknown regulators affect synthesis and degradation rates of the resulting proteins. To investigate the major principles of gene expression regulation in dynamic systems, we estimated protein synthesis and degradation rates from parallel time series data of mRNA and protein expression and tested the degree to which expression changes can be modeled by a simple linear differential equation. Examining three published datasets for yeast responding to diamide, rapamycin, and sodium chloride treatment, we find that almost one-third of genes can be well-modeled, and the estimated rates assume realistic values. Prediction quality is linked to low measurement noise and the shape of the expression profile. Synthesis and degradation rates do not correlate within one treatment, consistent with their independent regulation. When performing robustness analyses of the rate estimates, we observed that most genes adhere to one of two major modes of regulation, which we term synthesis- and degradation-independent regulation. These two modes, in which only one of the rates has to be tightly set, while the other one can assume various values, offer an efficient way for the cell to respond to stimuli and re-establish proteostasis. We experimentally validate degradation-independent regulation under oxidative stress for the heatshock protein Ssa4. PMID- 25111755 TI - Rapid peptidomic profiling of peritoneal fluid by MALDI-TOF mass spectrometry for the identification of biomarkers of endometriosis. AB - Peptidomic profiling of peritoneal fluid by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS) may represent a promising, suitable, rapid method for early diagnosis and staging of endometriosis. In a case-control study, peritoneal fluid was collected from 23 patients affected by endometriosis (eight minimal/mild endometriosis and 15 moderate/severe endometriosis) and six "endometriosis free" women undergoing laparoscopy. MALDI-TOF mass spectra of the peptide fraction extracted from peritoneal fluid samples lead to identify biomarkers potentially suitable for discriminating between peritoneal fluid samples from women affected by minimal/mild endometriosis and those from women affected by moderate/severe endometriosis. Peptidomic analysis of peritoneal fluid samples may define putative peptide biomarkers suitable for staging endometriosis and improve our understanding of the pathogenesis of endometriosis. PMID- 25111756 TI - Treatment of simple and complex endometrial non-atypical hyperplasia with natural progesterone: response rate to different doses. AB - The aim of this study is to evaluate the response rate to natural progesterone in non-atypical endometrial hyperplasia and to identify the lowest effective dose. A total of 197 patients of childbearing age with simple or complex hyperplasia were retrospectively identified. The women were treated with a cyclic administration of progesterone at different dosages (100 versus 200 versus 300 mg daily). Endometrial biopsies were performed at 6, 12, 18 months. In comparing progesterone to a regimen of no therapy, a significantly higher remission rate was observed in the progesterone group than in the latter (95 versus 75%, p = 0.05 for simple hyperplasia; 89 versus 35%, p < 0.001 for complex hyperplasia). Out of 60 women with simple hyperplasia, remission was observed in 9/11 (81.8%), 40/41 (97.5%) and 8/8 (100%) patients treated, respectively, with progesterone 100, 200 and 300 mg daily. Out of 72 women with complex hyperplasia, remission was observed in 3/5 (60%), 49/53 (92.4%) and 12/14 (85.7%) patients treated with progesterone 100, 200 and 300 mg daily, respectively. There was no statistically significant difference in the response rate in the two groups, neither with simple nor with complex hyperplasia. In conclusion, progesterone increased the regression rate of both simple and complex hyperplasia. PMID- 25111757 TI - Deferred intravitreal triamcinolone in diabetic eyes after phacoemulsification. AB - PURPOSE: Evaluation of diabetic macular edema (DME) after phacoemulsification by optical coherence tomography (OCT) and the use of deferred intravitreal triamcinolone acetonide (IVTA) as a therapy. METHODS: This was an institutional, nonrandomized, retrospective study. Within a period of 18 months, 5,684 eyes underwent phacoemulsification in our department, 1,634 of which were diabetic. Eight weeks after surgery, 55 out of 1,634 diabetic eyes that had undergone phacoemulsification developed DME and were treated with a 3.2 mg IVTA injection. The mean best-corrected visual acuity (BCVA) and mean central macular thickness (CMT) were measured before and after phacoemulsification and 3 months after IVTA. RESULTS: The mean BCVA at baseline, after phacoemulsification, and 3 months after deferred IVTA was 49.0+/-17.7, 53.7+/-17.4, and 66.36+/-20.66, respectively. The mean CMT for the same endpoints was 268.9+/-76.3, 554.6+/-137.8, and 275.0+/-76.3 MUm, respectively. Eyes were subdivided into 2 subgroups: eyes with a previous history of DME and eyes with de novo DME. Three months after deferred IVTA, there was a statistically significant difference between these 2 subgroups in BCVA (P<0.001) and in CMT (P=0.002). The OCT features before and after IVTA defined 2 subgroups of DME, with respect to cyst color and symmetry and OS/IS line integrity after IVTA. CONCLUSIONS: Our data suggest that DME progresses after uncomplicated phacoemulsification in diabetic eyes and that IVTA is an appropriate therapeutic tool. The response to IVTA treatment depends on previous history of DME and its OCT profile. PMID- 25111758 TI - Modulation of hunger and satiety: hormones and diet. AB - PURPOSE OF REVIEW: To highlight recent research developments relating to the effects of, and interactions between, hormones and diet, as well as underlying mechanisms, on appetite, energy intake and body weight. For this purpose, clinically relevant English language articles were reviewed from October 2012 to April 2014. RECENT FINDINGS: The mechanisms underlying nutrient-induced energy intake suppression differ between dietary protein and lipid. High-fat, energy dense diets compromise the satiating effects of gut hormones, and, therefore, promote further overconsumption. These effects are mediated by changes in the signalling in both peripheral and central pathways, and may only be partially reversible by dietary restriction. Additional factors, including probiotics, meal related factors (e.g., eating speed and frequency), circadian influences and gene polymorphisms, also modify energy intake and eating behaviour. SUMMARY: Research continues to unravel the pathways and mechanisms underlying the nutrient-induced and diet-induced regulation of energy intake, as well as the changes, both peripherally and in the central nervous system, brought about by the consumption of high-fat, energy-dense diets. Much further work is required to translate this knowledge into novel, and effective, approaches for the management and treatment of obesity and associated metabolic disorders. PMID- 25111759 TI - Blue native-PAGE analysis of membrane protein complexes in Porphyromonas gingivalis. AB - Membrane complexes of Porphyromonas gingivalis were analyzed using two dimensional-blue native-PAGE. The molecular mass of the gingipain complexes, RgpA and Kgp, ranged from 450 kDa to greater than 1200 kDa, and did not change in single rgpA and kgp mutants indicating that the proteolytically processed polyproteins were independently capable of forming complexes. The outer membrane protein, LptO, which is essential for gingipain secretion, was found in up to seven different complex sizes. PG0026, also important for secretion, was observed to interact with the largest LptO complex [VII] at 480 kDa, supporting a cooperative role in secretion. Two pro-form RgpB intermediates formed a complex before cleavage of their C-terminal secretion signal domains (CTDs) such that complex formation may occur during secretion and processing. This may also be the case for other CTD-proteins as not only modified, mature RgpB, but also CPG70 was found to exist as multi-subunit complexes. RagA and RagB were observed in three different complex sizes. Elimination of the abundant gingipains enabled the identification of many inner and outer membrane protein complexes: TonB:ExbB:ExbD, Omp85, P51:PG2168, PorK:PorN, PG0056, PG0241, PG1430 and five proposed respiratory chain complexes (Mmd, Nqr, Rnf, Frd/Sdh and Atp). BIOLOGICAL SIGNIFICANCE: Porphyromonas gingivalis is a major oral pathogen associated with chronic periodontitis in humans. Secreted gingipains are considered major virulence factors of this pathogen and are secreted by a newly described type IX secretion system. This work has used 2D-BN-PAGE and MS to demonstrate that mature gingipains can independently form complexes and that substrate intermediates and mature secreted proteins of the type IX secretion system form multi-subunit complexes. Based on this work we propose that the substrates of this secretion system are secreted as large multi-subunit protein complexes. Two known important components of the secretion machinery, PG0026 and the integral outer membrane protein, LptO, were found to interact which would anchor PG0026 to the outer membrane and perhaps aid in the function of PG0026 to cleave the CTD from secreted substrates. The work has also identified more than 100 membrane proteins forming multi-subunit complexes. PMID- 25111760 TI - Superficial dopants allow growth of silicone nanofilaments on hydroxyl-free substrates. AB - We report new types of silicone nanostructures by a gas-phase reaction of trichloromethylsilane: 1-D silicone nanofilaments with a raveled end and silicone nanoteeth. Filaments with a raveled end are obtained on poly(vinyl chloride), which is superficially doped with the detergent Span 20. Silicone nanoteeth grow on sodium chloride using dibutyl phthalate as superficial dopant. Without dopants, no structures are observed. The dopants are identified by mass spectroscopy and the silicone nanostructures are analyzed by infrared spectroscopy and energy-dispersive analysis of X-rays. The growth of silicone nanostructures on a hydrophobic substrate (poly(vinyl chloride)/Span 20) and a substrate free of hydroxyl groups (sodium chloride/dibutyl phthalate) questions the currently discussed mechanisms for the growth of 1-D silicone nanofilaments, which is discussed. We suggest superficial doping as an alternative pretreatment method to oxidizing activation and prove this principle by the successful coating of copper, which is superficially doped with Span 20. PMID- 25111762 TI - Reorientation osteotomy for the atypical clasp thumb in children with arthrogryposis. AB - Congenital thumb contractures are a well described but complex deformity to manage. Thumb contractures are common in patients with arthrogryposis. Many patients with arthrogryposis develop a supination, adduction, and flexion contracture at the thumb carpometacarpal join. Despite some thumb function, their thumb position and contracted first webspace precludes effective pinch or grasp, with the thumb opposing only to the palmar space. An extension, reorientation metacarpal osteotomy that places thumb in an efficient position has the potential to improve function in of these patients. This report provides a new classification system for congenital thumb deformities that can dictate management based upon thumb joint positions. We describe a previously unreported, arthrogrypotic thumb contracture that can be managed with an extension/pronation metacarpal osteotomy with simultaneous widening of the first webspace. PMID- 25111763 TI - Laboratory and field efficacy of entomopathogenic fungi for the management of the sweetpotato weevil, Cylas formicarius (Coleoptera: Brentidae). AB - The sweetpotato weevil, Cylas formicarius (F.) (Coleoptera: Brentidae), is one of the most important pests of sweet potatoes in the world. With free trade between the United States and the U.S.-controlled Mariana Islands, C. formicarius has spread along with this commodity. Because of the cryptic nature of the larvae and nocturnal activity of the adults, and the cancellation of long-residual pesticides, this pest has become increasingly difficult to control. Therefore, the present study sought to explore and to compare the effectiveness of Metarhizium brunneum F52 (90ml a.i./ha), Beauveria bassiana GHA (40ml a.i./ha), spinosad (90g a.i./ha), azadirachtin (1484ml a.i./ha), B. bassiana+M. brunneum (20ml a.i./ha+45ml a.i./ha), B. bassiana+azadirachtin (20ml a.i./ha+742ml a.i./ha), B. bassiana+spinosad (20ml a.i./ha+45ml a.i./ha), M. brunneum+azadirachtin (45ml a.i./ha+742ml a.i./ha) and M. brunneum+spinosad (45ml a.i./ha+45 grams a.i./ha) in controlling this pest in both the laboratory and the field. The treatment with B. bassiana+M. brunneum was the most effective in reducing tuber damage by C. formicarius, producing the highest yields. The most adult cadavers were found in plots treated with the combination of two fungi. This combined fungal formulation appears to be appropriate for the practical control of C. formicarius on sweet potatoes. PMID- 25111761 TI - Optimization of sentinel lymph node mapping in bladder cancer using near-infrared fluorescence imaging. AB - BACKGROUND AND OBJECTIVES: Unlike other cancers, the Sentinel Lymph Node (SLN) procedure in bladder cancer requires special attention to the injection technique. The aim of this study was to assess feasibility and to optimize tracer injection technique for SLN mapping in bladder cancer patients using NIR fluorescence imaging. METHODS: Twenty patients with invasive bladder cancer scheduled for radical cystectomy were prospectively enrolled. Indocyanine green (ICG) bound to human serum albumin (complex ICG:HSA; 500 uM) was injected peritumourally to permit SLN mapping. ICG:HSA was first administrated serosally (n = 5), and subsequently mucosally by cystoscopic injection (n = 15). In the last cohort of 12 patients treated with cystoscopic injection, the bladder was kept filled with saline for at least 15 min. RESULTS: Fluorescent lymph nodes were observed only in the patient group with cystoscopic injection of ICG:HSA. Filling of the bladder post-injection was of added value to promote drainage of ICG:HSA to the lymph nodes, and in 11 of these 12 patients (92%) one or more NIR fluorescent lymph nodes were identified. CONCLUSIONS: The current study demonstrates proof-of-principle of using NIR fluorescence imaging for SLN identification in bladder cancer. Cystoscopic injection with distension of the bladder appears optimal for SLN mapping. PMID- 25111765 TI - Template-derived carbon: an unexpected promoter for the creation of strong basicity on mesoporous silica. AB - Template-derived carbon is demonstrated to effectively promote the creation of strong basicity on mesoporous silica, for the first time. New materials owning ordered mesoporous structure, strong basicity, and excellent catalytic activity are thus successfully constructed at low temperatures, which are impossible to achieve using conventional methods. PMID- 25111766 TI - Reply to comment: Asociacion de Hemato-Oncologia Pediatrica de Centro America (AHOPCA): a model for sustainable development in pediatric oncology. PMID- 25111767 TI - A cell-surface-anchored ratiometric fluorescent probe for extracellular pH sensing. AB - Accurate sensing of the extracellular pH is a very important yet challenging task in biological and clinical applications. This paper describes the development of an amphiphilic lipid-DNA molecule as a simple yet useful cell-surface-anchored ratiometric fluorescent probe for extracellular pH sensing. The lipid-DNA probe, which consists of a hydrophobic diacyllipid tail and a hydrophilic DNA strand, is modified with two fluorescent dyes; one is pH-sensitive as pH indicator and the other is pH-insensitive as an internal reference. The lipid-DNA probe showed sensitive and reversible response to pH change in the range of 6.0-8.0, which is suitable for most extracellular studies. In addition, based on simple hydrophobic interactions with the cell membrane, the lipid-DNA probe can be easily anchored on the cell surface with negligible cytotoxicity, excellent stability, and unique ratiometric readout, thus ensuring its accurate sensing of extracellular pH. Finally, this lipid-DNA-based ratiometric pH indicator was successfully used for extracellular pH sensing of cells in 3D culture environment, demonstrating the potential applications of the sensor in biological and medical studies. PMID- 25111768 TI - Selective uptake of cylindrical poly(2-oxazoline) brush-antiDEC205 antibody-OVA antigen conjugates into DEC-positive dendritic cells and subsequent T-cell activation. AB - To achieve specific cell targeting by various receptors for oligosaccharides or antibodies, a carrier must not be taken up by any of the very many different cells and needs functional groups prone to clean conjugation chemistry to derive well-defined structures with a high biological specificity. A polymeric nanocarrier is presented that consists of a cylindrical brush polymer with poly-2 oxazoline side chains carrying an azide functional group on each of the many side chain ends. After click conjugation of dye and an anti-DEC205 antibody to the periphery of the cylindrical brush polymer, antibody-mediated specific binding and uptake into DEC205(+) -positive mouse bone marrow-derived dendritic cells (BMDC) was observed, whereas binding and uptake by DEC205(-) negative BMDC and non-DC was essentially absent. Additional conjugation of an antigen peptide yielded a multifunctional polymer structure with a much stronger antigen-specific T-cell stimulatory capacity of pretreated BMDC than application of antigen or polymer-antigen conjugate. PMID- 25111770 TI - The development of time-based prospective memory in childhood: the role of working memory updating. AB - This large-scale study examined the development of time-based prospective memory (PM) across childhood and the roles that working memory updating and time monitoring play in driving age effects in PM performance. One hundred and ninety seven children aged 5 to 14 years completed a time-based PM task where working memory updating load was manipulated within individuals using a dual task design. Results revealed age-related increases in PM performance across childhood. Working memory updating load had a negative impact on PM performance and monitoring behavior in older children, but this effect was smaller in younger children. Moreover, the frequency as well as the pattern of time monitoring predicted children's PM performance. Our interpretation of these results is that processes involved in children's PM may show a qualitative shift over development from simple, nonstrategic monitoring behavior to more strategic monitoring based on internal temporal models that rely specifically on working memory updating resources. We discuss this interpretation with regard to possible trade-off effects in younger children as well as alternative accounts. PMID- 25111771 TI - Thirty-day readmission rates after PCI in a metropolitan center in Europe: incidence and impact on prognosis. AB - INTRODUCTION: Thirty-day readmission rates after percutaneous coronary intervention (PCI) have been related to adverse prognosis, and represent one of the most investigated indicators of quality of care. These data, however, derive from non-European centers evaluating all-cause readmissions, without stratification for diagnosis. METHODS: All consecutive patients undergoing PCI at our center from January 2009 to December 2011 were enrolled. Thirty-day readmissions related to postinfarction angina, myocardial infarction, unstable angina or heart failure were defined as acute coronary syndrome (ACS) or heart failure rehospitalizations. Major cardiac adverse event (MACE) was the primary outcome, and its single components (death, myocardial infarction and repeated revascularization) the secondary ones. RESULTS: A total of 1192 patients were included; among them, 53 (4.7%) were readmitted within 30 days, and 25 (2.1%) were classified as ACS/heart failure related. During hospitalization, patients with ACS/heart failure readmissions were more likely to suffer a periprocedural myocardial infarction (22 vs. 4%; P = 0.012), and to undergo PCI at 30 days (52 vs. 0.5%; P < 0.001). Logistic regression analysis indicated that periprocedural myocardial infarction represented the only independent predictor of an ACS/heart failure readmission [odds ratio (OR) 4.5; 1.1-16.8; P = 0.047]. After a median follow-up of 787 days (434-1027; first and third quartiles), patients with a 30 day ACS/heart failure readmission experienced higher rates of MACE, all-cause death and myocardial infarction (64 vs. 21%, P < 0.001; 28 vs. 6%, P = 0.017; and 20 vs. 2.7%, P < 0.001, respectively). Cox multivariate analysis indicated that ACS/heart failure 30-day readmissions were independently related to an increased risk of all-cause death (OR 3.3; 1.1-8.8; P = 0.02), differently from 30-day non ACS/heart failure readmissions (OR 3.1; 0.7-12.9; P = 0.12). CONCLUSION: Thirty day readmissions after PCI in an Italian center are infrequent, and only those patients with ACS/heart failure show a detrimental impact on prognosis who have periprocedural myocardial infarction as the only independent predictor. PMID- 25111772 TI - Rat models reveal differences in cardiocirculatory profile between Takotsubo syndrome and acute myocardial infarction. AB - AIMS: Takotsubo syndrome, also known as stress-induced cardiomyopathy, is an important differential diagnosis in patients presenting with chest pain and is associated with significant morbidity and mortality. Beyond adrenergic overstimulation the pathophysiology behind Takotsubo is poorly known and the syndrome cannot be differentiated from acute myocardial infarction (AMI) by non invasive tests. Despite the facts that Takotsubo syndrome and AMI may differ in many important aspects and that potential mechanistic similarities and/or differences between Takotsubo syndrome and AMI have not been established, Takotsubo syndrome patients are treated according to guidelines developed for AMI and acute heart failure. The aim of this article was to assess whether cardiac function and hemodynamic indices differ between rat models of Takotsubo syndrome and AMI. METHODS: Male Sprague-Dawley rats were randomized to the Takotsubo syndrome (50 mg/kg intraperitoneally isoprenaline) or AMI [permanent left anterior descending coronary artery (LAD) ligation] models. Two hours post isoprenaline or LAD ligation, arterial and intraventricular pressures were recorded and cardiac function was studied by echocardiography. In another subset of Takotsubo syndrome rats, pharmacological intervention aimed at maintaining systolic blood pressure more than 90 mmHg with either norepinephrine or phenylephrine was compared with saline. RESULTS: Left ventricular end-diastolic pressure was significantly lower and estimates of cardiac function were significantly better in Takotsubo syndrome rats compared with AMI rats. Vasopressor treatment was associated with increased mortality in Takotsubo syndrome rats (P < 0.05). CONCLUSION: Takotsubo syndrome and AMI are associated with different cardiocirculatory profiles. Extrapolation of treatment strategies across the syndromes may therefore not be appropriate. PMID- 25111773 TI - Usefulness of EuroSCORE systems for risk stratification. AB - Risk stratification of patients undergoing open-heart surgery or percutaneous interventions may help physicians select the best individual management of patients with advanced heart disease.European System for Cardiac Operative Risk Evaluation (EuroSCORE) is an easy-to-calculate, clinical scoring system which has been developed for coronary surgery and applied in various cardiological settings. Recently, the EuroSCORE II model has been launched with the aim of improving the stratification performance over the first model.In the present study, we review the available scientific data on the use of EuroSCORE systems in patients undergoing surgical or percutaneous procedures. PMID- 25111774 TI - Coronary plaque ulceration documented at sequential angiography and confirmed by optical coherence tomography in a patient with recurrent acute coronary syndrome. AB - : A 51-year-old man was hospitalized for recurrence of acute coronary syndrome after few months. Coronary angiography during first hospitalization showed no significant coronary stenosis, while the second time, right coronary artery presented an expansion at the proximal segment. Optical coherence tomography documented a long fibroatheroma with an ulceration and residual white thrombus. PMID- 25111769 TI - Recognition and repair of chemically heterogeneous structures at DNA ends. AB - Exposure to environmental toxicants and stressors, radiation, pharmaceutical drugs, inflammation, cellular respiration, and routine DNA metabolism all lead to the production of cytotoxic DNA strand breaks. Akin to splintered wood, DNA breaks are not "clean." Rather, DNA breaks typically lack DNA 5'-phosphate and 3' hydroxyl moieties required for DNA synthesis and DNA ligation. Failure to resolve damage at DNA ends can lead to abnormal DNA replication and repair, and is associated with genomic instability, mutagenesis, neurological disease, ageing and carcinogenesis. An array of chemically heterogeneous DNA termini arises from spontaneously generated DNA single-strand and double-strand breaks (SSBs and DSBs), and also from normal and/or inappropriate DNA metabolism by DNA polymerases, DNA ligases and topoisomerases. As a front line of defense to these genotoxic insults, eukaryotic cells have accrued an arsenal of enzymatic first responders that bind and protect damaged DNA termini, and enzymatically tailor DNA ends for DNA repair synthesis and ligation. These nucleic acid transactions employ direct damage reversal enzymes including Aprataxin (APTX), Polynucleotide kinase phosphatase (PNK), the tyrosyl DNA phosphodiesterases (TDP1 and TDP2), the Ku70/80 complex and DNA polymerase beta (POLbeta). Nucleolytic processing enzymes such as the MRE11/RAD50/NBS1/CtIP complex, Flap endonuclease (FEN1) and the apurinic endonucleases (APE1 and APE2) also act in the chemical "cleansing" of DNA breaks to prevent genomic instability and disease, and promote progression of DNA- and RNA-DNA damage response (DDR and RDDR) pathways. Here, we provide an overview of cellular first responders dedicated to the detection and repair of abnormal DNA termini. PMID- 25111776 TI - Highly efficient fluorescent interstrand photo-crosslinking of DNA duplexes labeled with 5-fluoro-4-thio-2'-o-methyluridine. AB - The formation of a fluorescent photoadduct between 5-fluoro-4-thiouridine ((FS) U), in the sequence context 5'-A(FS) UA-3' and incorporated into a synthetic oligonucleotide either at its 3'- or 5'-end, and one of the thymines of the TAT motif in a complementary target DNA strand led to photo-crosslinking of the two strands for several oligonucleotide constructs. Enzymatic digestion, MS, UV, and fluorescence spectral analyses of the interstrand crosslinked oligonucleotides revealed the identity of the thymidine that participates in the photo crosslinking reaction as well as the diastereomeric structures of the crosslinks. The proposed pathways of interstrand photo-crosslinking are supported by experiments with isotopically labeled oligonucleotide constructs and visualized by means of molecular dynamics simulations. PMID- 25111777 TI - A rare case of uterine rupture due to a placental site trophoblastic tumour in the rudimentary horn. PMID- 25111775 TI - Brief exposure to cigarette smoke impairs airway epithelial cell innate anti viral defence. AB - BACKGROUND: Human rhinovirus (hRV) infections commonly cause acute upper respiratory infections and asthma exacerbations. Environmental cigarette smoke exposure is associated with a significant increase in the risk for these infections in children. OBJECTIVE: To determine the impact of short-term exposure to cigarette smoke on innate immune responses of airway epithelial cells infected with hRV. METHODS: A human bronchial epithelial cell line (HBEC-3KT) was exposed to cigarette smoke extract (CSE) for 30 min and subsequently infected with hRV serotype 1B. Viral-induced cytokine release was measured with AlphaLISA and viral replication quantified by shed viral titer and intracellular viral copy number 24h post-infection. RESULTS: CSE induced a concentration-dependent decrease in CXCL10 (p<0.001) and IFN-beta (p<0.001), with a 79% reduction at the highest dose with an associated 3-fold increase in shed virus. These effects were maintained when infection was delayed up to 24h post CSE exposure. Exogenous IFN-beta treatment at t=0 after infection blunts the effects of CSE on viral replication (p<0.05). CONCLUSION: A single exposure of 30 min to cigarette smoke has a lasting impact on epithelial innate defence providing a plausible mechanism for the increase in respiratory infections seen in children exposed to second-hand tobacco smoke. PMID- 25111778 TI - Theoretical investigation on carbon nucleation on nickel carbides at initial stages of single-walled carbon nanotube formation. AB - It is a long-standing controversy whether metal carbide clusters do exist during the nucleation and growth process of single-walled carbon nanotubes (SWCNTs). In the current work, we are trying to elucidate the carbon nucleation on nickel carbides during the initial stages based on density functional theory calculated formation energy and chemical potential for a series of Ni55Cn carbides (n is the number of carbon atoms dissolved in the Ni55 cluster). It is found that the formation energies of the Ni55Cn carbides decrease gradually with an increase of dissolved carbon atomic numbers, meaning the Ni55Cn carbides are thermodynamically stable. Meanwhile, the calculated chemical potentials indicate that not only nickel carbides are preferentially formed during the initial stage of the SWCNT nucleation, but also saturated nickel carbides may be able to exist during the nucleation and growth process of SWCNTs. In addition, the nickel carbides have a high selectivity for the formation of the carbon pentagon and carbon structures with pentagon-incorporated end-edge according to the adsorption energies. All of these findings provide opportunities in controlling the growth of the SWCNTs. PMID- 25111782 TI - A four-stage hybrid model for hydrological time series forecasting. AB - Hydrological time series forecasting remains a difficult task due to its complicated nonlinear, non-stationary and multi-scale characteristics. To solve this difficulty and improve the prediction accuracy, a novel four-stage hybrid model is proposed for hydrological time series forecasting based on the principle of 'denoising, decomposition and ensemble'. The proposed model has four stages, i.e., denoising, decomposition, components prediction and ensemble. In the denoising stage, the empirical mode decomposition (EMD) method is utilized to reduce the noises in the hydrological time series. Then, an improved method of EMD, the ensemble empirical mode decomposition (EEMD), is applied to decompose the denoised series into a number of intrinsic mode function (IMF) components and one residual component. Next, the radial basis function neural network (RBFNN) is adopted to predict the trend of all of the components obtained in the decomposition stage. In the final ensemble prediction stage, the forecasting results of all of the IMF and residual components obtained in the third stage are combined to generate the final prediction results, using a linear neural network (LNN) model. For illustration and verification, six hydrological cases with different characteristics are used to test the effectiveness of the proposed model. The proposed hybrid model performs better than conventional single models, the hybrid models without denoising or decomposition and the hybrid models based on other methods, such as the wavelet analysis (WA)-based hybrid models. In addition, the denoising and decomposition strategies decrease the complexity of the series and reduce the difficulties of the forecasting. With its effective denoising and accurate decomposition ability, high prediction precision and wide applicability, the new model is very promising for complex time series forecasting. This new forecast model is an extension of nonlinear prediction models. PMID- 25111779 TI - Pleiotropic functions for transcription factor zscan10. AB - The transcription factor Zscan10 had been attributed a role as a pluripotency factor in embryonic stem cells based on its interaction with Oct4 and Sox2 in in vitro assays. Here we suggest a potential role of Zscan10 in controlling progenitor cell populations in vivo. Mice homozygous for a Zscan10 mutation exhibit reduced weight, mild hypoplasia in the spleen, heart and long bones and phenocopy an eye malformation previously described for Sox2 hypomorphs. Phenotypic abnormalities are supported by the nature of Zscan10 expression in midgestation embryos and adults suggesting a role for Zscan10 in either maintaining progenitor cell subpopulation or impacting on fate choice decisions thereof. PMID- 25111780 TI - Shedding of a low pathogenic avian influenza virus in a common synanthropic mammal--the cottontail rabbit. AB - BACKGROUND: Cottontails (Sylvilagus spp.) are common mammals throughout much of the U.S. and are often found in peridomestic settings, potentially interacting with livestock and poultry operations. If these animals are susceptible to avian influenza virus (AIV) infections and shed the virus in sufficient quantities they may pose a risk for movement of avian influenza viruses between wildlife and domestic animals in certain situations. METHODOLOGY/PRINCIPAL FINDINGS: To assess the viral shedding potential of AIV in cottontails, we nasally inoculated fourteen cottontails with a low pathogenic AIV (H4N6). All inoculated cottontails shed relatively large quantities of viral RNA both nasally (<= 10(6.94) PCR EID50 equivalents/mL) and orally (<= 10(5.09) PCR EID50 equivalents/mL). However, oral shedding tended to decline more quickly than did nasal shedding. No animals showed any obvious signs of disease throughout the study. Evidence of a serological response was found in all infected rabbits at 22 days post infection in convalescent sera. CONCLUSIONS/SIGNIFICANCE: To our knowledge, cottontails have not been previously assessed for AIV shedding. However, it was obvious that they shed AIV RNA extensively via the nasal and oral routes. This is significant, as cottontails are widely distributed throughout the U.S. and elsewhere. These mammals are often found in highly peridomestic situations, such as farms, parks, and suburban neighborhoods, often becoming habituated to human activities. Thus, if infected these mammals could easily transport AIVs short distances. PMID- 25111781 TI - Evolutionary stability in the asymmetric volunteer's dilemma. AB - It is often assumed that in public goods games, contributors are either strong or weak players and each individual has an equal probability of exhibiting cooperation. It is difficult to explain why the public good is produced by strong individuals in some cooperation systems, and by weak individuals in others. Viewing the asymmetric volunteer's dilemma game as an evolutionary game, we find that whether the strong or the weak players produce the public good depends on the initial condition (i.e., phenotype or initial strategy of individuals). These different evolutionarily stable strategies (ESS) associated with different initial conditions, can be interpreted as the production modes of public goods of different cooperation systems. A further analysis revealed that the strong player adopts a pure strategy but mixed strategies for the weak players to produce the public good, and that the probability of volunteering by weak players decreases with increasing group size or decreasing cost-benefit ratio. Our model shows that the defection probability of a "strong" player is greater than the "weak" players in the model of Diekmann (1993). This contradicts Selten's (1980) model that public goods can only be produced by a strong player, is not an evolutionarily stable strategy, and will therefore disappear over evolutionary time. Our public good model with ESS has thus extended previous interpretations that the public good can only be produced by strong players in an asymmetric game. PMID- 25111783 TI - Trimethoprim use before pregnancy and risk of congenital malformation: reanalyzed using a case-crossover design and a case-time-control design. AB - PURPOSE: Studies on the safety of drugs used during pregnancy are necessary and important but prone to bias. Using cases as their own controls can reduce bias. We used a case-crossover design and a case-time-control design to estimate the risk of congenital malformation (CM) for children born to mothers who redeemed a trimethoprim prescription shortly before pregnancy. METHODS: The study was based on all live born singletons (N = 685 600) in Denmark whose mothers had available information on prescriptions in the Danish National Prescription Registry between 1996 and 2008. We defined 1-3 months before pregnancy as a potential risk period and 13-15 months before pregnancy as a reference period. Two other reference periods were used (7-9 months before pregnancy and months 4-6 of pregnancy). The case-crossover design is dependent on the assumption of a stable trimethoprim prescription over the study period in the source population. To estimate the trend of trimethoprim prescriptions, we used a control group comprising children without CMs. RESULTS: Both study designs showed children had a higher risk of overall CM [odds ratio of 1.66, 95% confidence interval (CI): 1.10-2.53 and 1.50, 95%CI: 0.66-3.38, respectively] if their mothers had a trimethoprim prescription in the 3 months before pregnancy and subtypes of CM for example in the musculoskeletal system, which were consistent to the previous findings from a cohort study. CONCLUSIONS: This study corroborates that trimethoprim is a potential teratogen when used 3 months before pregnancy and demonstrates the value of case-only approaches for studying, for example, adverse effects of antibiotics in reproductive epidemiology. PMID- 25111784 TI - Hypomethylation of the paternally inherited LRRTM1 promoter linked to schizophrenia. AB - Epigenetic effects on psychiatric traits remain relatively under-studied, and it remains unclear what the sizes of individual epigenetic effects may be, or how they vary between different clinical populations. The gene LRRTM1 (chromosome 2p12) has previously been linked and associated with schizophrenia in a parent-of origin manner in a set of affected siblings (LOD = 4.72), indirectly suggesting a disruption of paternal imprinting at this locus in these families. From the same set of siblings that originally showed strong linkage at this locus, we analyzed 99 individuals using 454-bisulfite sequencing, from whole blood DNA, to measure the level of DNA methylation in the promoter region of LRRTM1. We also assessed seven additional loci that would be informative to compare. Paternal identity-by descent sharing at LRRTM1, within sibling pairs, was linked to their similarity of methylation at the gene's promoter. Reduced methylation at the promoter showed a significant association with schizophrenia. Sibling pairs concordant for schizophrenia showed more similar methylation levels at the LRRTM1 promoter than diagnostically discordant pairs. The alleles of common SNPs spanning the locus did not explain this epigenetic linkage, which can therefore be considered as largely independent of DNA sequence variation and would not be detected in standard genetic association analysis. Our data suggest that hypomethylation at the LRRTM1 promoter, particularly of the paternally inherited allele, was a risk factor for the development of schizophrenia in this set of siblings affected with familial schizophrenia, and that had previously showed linkage at this locus in an affected-sib-pair context. PMID- 25111787 TI - Transfer hydrogenation as a redox process in nucleotides. AB - Using a combined theoretical and experimental strategy, the heats of hydrogenation of the nucleotide bases uracil, thymine, cytosine, adenine, and guanine have been determined. The most easily hydrogenated base is uracil, followed by thymine and cytosine. Comparison of these hydrogenation enthalpies with those of ketones and aldehydes derived from sugar models indicates the possibility of near-thermoneutral hydrogen transfer between uracil and the sugar phosphate backbone in oligonucleotides. PMID- 25111786 TI - Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat. AB - Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID- 25111785 TI - Common and rare variant analysis in early-onset bipolar disorder vulnerability. AB - Bipolar disorder is one of the most common and devastating psychiatric disorders whose mechanisms remain largely unknown. Despite a strong genetic contribution demonstrated by twin and adoption studies, a polygenic background influences this multifactorial and heterogeneous psychiatric disorder. To identify susceptibility genes on a severe and more familial sub-form of the disease, we conducted a genome-wide association study focused on 211 patients of French origin with an early age at onset and 1,719 controls, and then replicated our data on a German sample of 159 patients with early-onset bipolar disorder and 998 controls. Replication study and subsequent meta-analysis revealed two genes encoding proteins involved in phosphoinositide signalling pathway (PLEKHA5 and PLCXD3). We performed additional replication studies in two datasets from the WTCCC (764 patients and 2,938 controls) and the GAIN-TGen cohorts (1,524 patients and 1,436 controls) and found nominal P-values both in the PLCXD3 and PLEKHA5 loci with the WTCCC sample. In addition, we identified in the French cohort one affected individual with a deletion at the PLCXD3 locus and another one carrying a missense variation in PLCXD3 (p.R93H), both supporting a role of the phosphatidylinositol pathway in early-onset bipolar disorder vulnerability. Although the current nominally significant findings should be interpreted with caution and need replication in independent cohorts, this study supports the strategy to combine genetic approaches to determine the molecular mechanisms underlying bipolar disorder. PMID- 25111789 TI - Low yield of outpatient serum folate testing: eleven years of experience. PMID- 25111788 TI - White matter tractography in early psychosis: clinical and neurocognitive associations. AB - BACKGROUND: While many diffusion tensor imaging (DTI) investigations have noted disruptions to white matter integrity in individuals with chronic psychotic disorders, fewer studies have been conducted in young people at the early stages of disease onset. Using whole tract reconstruction techniques, the aim of this study was to identify the white matter pathology associated with the common clinical symptoms and executive function impairments observed in young people with psychosis. METHODS: We obtained MRI scans from young people with psychosis and healthy controls. Eighteen major white matter tracts were reconstructed to determine group differences in fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) and then were subsequently correlated with symptomatology and neurocognitive performance. RESULTS: Our study included 42 young people with psychosis (mean age 23 yr) and 45 healthy controls (mean age 25 yr). Compared with the control group, the psychosis group had reduced FA and AD in the left inferior longitudinal fasciculus (ILF) and forceps major indicative of axonal disorganization, reduction and/or loss. These changes were associated with worse overall psychiatric symptom severity, increases in positive and negative symptoms, and worse current levels of depression. The psychosis group also showed FA reductions in the left superior longitudinal fasciculus that were associated with impaired neurocognitive performance in attention and semantic fluency. LIMITATIONS: Our analysis grouped 4 subcategories of psychosis together, and a larger follow-up study comparing affective and nonaffective psychoses is warranted. CONCLUSION: Our findings suggest that impaired axonal coherence in the left ILF and forceps major underpin psychiatric symptoms in young people in the early stages of psychosis. PMID- 25111790 TI - Inhibin alpha-subunit (INHA) expression in adrenocortical cancer is linked to genetic and epigenetic INHA promoter variation. AB - Adrenocortical carcinoma (ACC) is a rare, but highly malignant tumor of unknown origin. Inhibin alpha-subunit (Inha) knockout mice develop ACCs following gonadectomy. In man, INHA expression varies widely within ACC tissues and its circulating peptide inhibin pro-alphaC has been described as a novel tumor marker for ACC. We investigated whether genetic and epigenetic changes of the INHA gene in human ACC cause loss or variation of INHA expression. To this end, analyses of INHA sequence, promoter methylation and mRNA expression were performed in human adrenocortical tissues. Serum inhibin pro-alphaC levels were also measured in ACC patients. INHA genetic analysis in 37 unique ACCs revealed 10 novel, heterozygous rare variants. Of the 3 coding bases affected, one variant was synonymous and two were missense variants: S72F and S184F. The minor allele of rs11893842 at -124 bp was observed at a low frequency (24%) in ACC samples and was associated with decreased INHA mRNA levels: 4.7+/-1.9 arbitrary units for AA, compared to 26+/-11 for AG/GG genotypes (P = 0.034). The methylation of four proximal INHA promoter CpGs was aberrantly increased in five ACCs (47.7+/-3.9%), compared to normal adrenals (18.4+/-0.6%, P = 0.0052), whereas the other 14 ACCs studied showed diminished promoter methylation (9.8+/-1.1%, P = 0.020). CpG methylation was inversely correlated to INHA mRNA levels in ACCs (r = -0.701, p = 0.0036), but not associated with serum inhibin pro-alphaC levels. In conclusion, aberrant methylation and common genetic variation in the INHA promoter occur in human ACCs and are associated with decreased INHA expression. PMID- 25111793 TI - Surgical clipping of a basilar perforator artery aneurysm: a case of avoiding perforator sacrifice. AB - BACKGROUND: Aneurysms arising from basilar perforator arteries are very rare. A primary goal of surgery is always preservation of perforator flow. However, in most surgically managed cases in the literature, sacrifice of the perforator was reported. It is important for the literature to demonstrate that patency of the perforator is an achievable goal. OBJECTIVE: To present the second reported case of perforator flow preservation in the surgical management of basilar perforator artery aneurysms. CLINICAL PRESENTATION: A 45-year-old woman presented with World Federation of Neurologic Surgeons grade 1 subarachnoid hemorrhage. Digital subtraction angiography ultimately revealed a 2-mm aneurysm of the basilar artery arising from a perforator after an initially negative angiogram. Clipping was performed with perforator patency confirmed on direct inspection and intraoperative angiography. The patient's postoperative course was uneventful, and postoperative magnetic resonance imaging (MRI) showed no evidence of brainstem stroke. CONCLUSION: Although patency of the perforator is a rather obvious goal of cerebrovascular surgery, the current literature does not reflect an ability to do so in the case of basilar perforator aneurysms. We present only the second reported case of maintenance of perforator flow after clipping of a basilar perforator artery aneurysm. PMID- 25111792 TI - Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies. AB - BACKGROUND AND OBJECTIVE: A number of studies have assessed the relationship between beta-2 adrenergic receptor (ADRB2) gene polymorphisms and asthma risk. However, the results are inconsistent. A meta-analysis that focused on the association between asthma and all ADRB2 polymorphisms with at least three case control studies was thus performed. METHODS: A literature search of the PubMed, Embase, Web of Science, CNKI, and Wangfang databases was conducted. Odds ratios with 95% confidence intervals were used to assess the strength of associations. RESULTS: Arg16Gly, Gln27Glu, Thr164Ile, and Arg19Cys single nucleotide polymorphisms (SNPs) were identified in 46 case-control studies. The results showed that not all of the SNPs were associated with asthma in the overall population. Significant associations were found for the Arg16Gly polymorphism in the South American population via dominant model comparison (OR = 1.754, 95% CI = 1.179-2.609, I2 = 16.9%, studies = 2, case = 314, control = 237) in an analysis stratified by ethnicity. For the Gln27Glu polymorphism, a protective association was found in children via recessive model comparison (OR = 0.566, 95% CI = 0.417-0.769, I2 = 0.0%, studies = 11, case = 1693, control = 502) and homozygote genotype comparison (OR = 0.610, 95% CI = 0.434-0.856, I2 = 0.0%, studies = 11, case = 1693, control = 1502), and in adults via dominant model comparison (OR = 0.864, 95% CI = 0.768-0.971, I2 = 46.9%, n = 18, case = 3160, control = 3433). CONCLUSIONS: None of the ADRB2 gene polymorphisms were reproducibly associated with a risk of asthma across ethnic groups in the general population. PMID- 25111794 TI - A novel high-resolution single locus sequence typing scheme for mixed populations of Propionibacterium acnes in vivo. AB - The Gram-positive anaerobic bacterium Propionibacterium acnes is a prevalent member of the normal skin microbiota of human adults. In addition to its suspected role in acne vulgaris it is involved in a variety of opportunistic infections. Multi-locus sequence-typing (MLST) schemes identified distinct phylotypes associated with health and disease. Being based on 8 to 9 house keeping genes these MLST schemes have a high discriminatory power, but their application is time- and cost-intensive. Here we describe a single-locus sequence typing (SLST) scheme for P. acnes. The target locus was identified with a genome mining approach that took advantage of the availability of representative genome sequences of all known phylotypes of P. acnes. We applied this SLST on a collection of 188 P. acnes strains and demonstrated a resolution comparable to that of existing MLST schemes. Phylogenetic analysis applied to the SLST locus resulted in clustering patterns identical to a reference tree based on core genome sequences. We further demonstrate that SLST can be applied to detect multiple phylotypes in complex microbial communities by a metagenomic pyrosequencing approach. The described SLST strategy may be applied to any bacterial species with a basically clonal population structure to achieve easy typing and mapping of multiple phylotypes in complex microbiotas. The P. acnes SLST database can be found at http://medbac.dk/slst/pacnes. PMID- 25111796 TI - Adsorption of small molecules on helical gold nanorods: a relativistic density functional study. AB - We study the adsorption of a variety of small molecules on helical gold nanorods using relativistic density functional theory. We focus on Au40 which consists of a central linear strand of five gold atoms with seven helical strands of five gold atoms on a coaxial tube. All molecules preferentially adsorb at a single low coordinated gold atom on the coaxial tube at an end of Au40. In most cases, there is significant charge transfer (CT) between Au40 and the adsorbate, for CO and NO2, there is CT from the Au40 to adsorbate while for all other molecules there is CT from the adsorbate to Au40. Thus, Au40-adsorbate can be described as a donor-accepter complex and we use charge decomposition analysis to better understand the adsorption process. We determine the adsorption energy order to be C5H5N >NO2 > CO > NH3 > CH2=CH2 > CH2=CH-CHO > NO > HC=CH > H2S > SO2 > HCN > CH3OH > H2C=O > O2 > H2O > CH4 > N2. We find that the Au-C, Au-N, Au-S, and Au O bonds are surprisingly strong, with clear implications for reactivity enhancement of the adsorbate. The Au-H bond is relatively weak but, for interactions via an H atom that is bonded to a carbon atom (e.g., CH4), we find that there is large charge polarization of the Au-H-C moiety and partial activation of the inert C-H bond. Although the Au-S and Au-O bonds are generally weaker than the Au-C and Au-N bonds, we find that adsorption of H2S or H2O causes greater distortion of Au40 in the binding region. However, the degree of distortion is small and the helical structure is retained, demonstrating the stability of the helical Au40 nanorod under perturbations. PMID- 25111795 TI - An animal model for laryngotracheal injuries: an experimental study. AB - OBJECTIVES/HYPOTHESIS: To establish an animal model for post-intubation laryngotracheal injuries resulting in significant laryngotracheal insult without compromising the survival of the animal for a minimum period of 12 weeks post extubation. To study the extent of injury based on morphometric and histopathological change seen at 12 weeks post-extubation. STUDY DESIGN: Randomized block, single-blinded, experimental study. METHODS: Twelve New Zealand white rabbits were used in this study. The rabbits were randomly divided into three groups depending on the duration of intubation (6 hours, 4 hours, and 2 hours, respectively). The technique of intubation was standardized. Post extubation, these rabbits were humanely sacrificed after observation for 12 weeks or when they developed severe respiratory distress. The larynx and trachea were subjected to gross and histopathological examination. RESULTS: Histopathological examination and statistical analysis showed significant subglottic injury in all group B rabbits (intubated for 4 hours), and all of them survived for 12 weeks. CONCLUSION: In this study, an animal model for inducing and studying laryngotracheal injuries due to endotracheal intubation has been established. This study has the potential applications in research on etiopathogenesis and management of post-intubation laryngotracheal injuries. PMID- 25111797 TI - Broadening the spectrum of actin-based protrusive activity mediated by Arp2/3 complex-facilitated polymerization: motility of cytoplasmic ridges and tubular projections. AB - Arp2/3 complex-facilitated actin polymerization plays an essential role in a variety of cellular functions including motility, adherence, endocytosis, and trafficking. In the present study, we employ the sea urchin coelomocyte experimental model system to test the hypotheses that Arp2/3 complex-nucleated actin assembly mediates the motility of two unusual cellular protrusions; the cytoplasmic ridges present during coelomocyte spreading, and inducible, tubular shaped, and neurite-like projections. Our investigations couple pharmacological manipulation employing inhibitors of actin polymerization and the Arp2/3 complex with a wide array of imaging methods including digitally enhanced phase contrast, DIC, and polarization light microscopy of live cells; conventional, confocal and super-resolution light microscopy of fluorescently labeled cells; and scanning and transmission electron microscopy. Taken together, the results of this study indicate that Arp2/3 complex-facilitated actin polymerization underlies the motility of coelomocyte cytoplasmic ridges and tubular projections, that these processes are related to each other, and that they have been preliminarily identified in other cell types. The results also highlight the broad spectrum of actin-based protrusive activities dependent on the Arp2/3 complex and provide additional insights into the pervasive nature of this ubiquitous actin nucleator. Furthermore, we provide the first evidence of a possible mechanistic difference between the impacts of the small molecule drugs BDM and CK666 on the Arp2/3 complex. PMID- 25111798 TI - Direct imaging of functional networks. AB - In blood-oxygenation-level-dependent functional magnetic resonance imaging (fMRI), current methods typically acquire ~ 500,000 imaging voxels at each time point, and then use computer algorithms to reduce this data to the coefficients of a few hundred parcels or networks. This suggests that the amount of relevant information present in the fMRI signal is relatively small, and presents an opportunity to greatly improve the speed and signal to noise ratio (SNR) of the fMRI process. In this work, a theoretical framework is presented for calculating the coefficients of functional networks directly from highly undersampled fMRI data. Using predefined functional parcellations or networks and a compact k-space trajectory that samples data at optimal spatial scales, the problem of estimating network coefficients is reformulated to allow for direct least squares estimation, without Fourier encoding. By simulation, this approach is shown to allow for acceleration of the imaging process under ideal circumstances by nearly three orders of magnitude. PMID- 25111800 TI - Methodology to improve design of accelerated life tests in civil engineering projects. AB - For reliability testing an Energy Expansion Tree (EET) and a companion Energy Function Model (EFM) are proposed and described in this paper. Different from conventional approaches, the EET provides a more comprehensive and objective way to systematically identify external energy factors affecting reliability. The EFM introduces energy loss into a traditional Function Model to identify internal energy sources affecting reliability. The combination creates a sound way to enumerate the energies to which a system may be exposed during its lifetime. We input these energies into planning an accelerated life test, a Multi Environment Over Stress Test. The test objective is to discover weak links and interactions among the system and the energies to which it is exposed, and design them out. As an example, the methods are applied to the pipe in subsea pipeline. However, they can be widely used in other civil engineering industries as well. The proposed method is compared with current methods. PMID- 25111802 TI - Are there consistent grazing indicators in Drylands? Testing plant functional types of various complexity in South Africa's Grassland and Savanna Biomes. AB - Despite our growing knowledge on plants' functional responses to grazing, there is no consensus if an optimum level of functional aggregation exists for detecting grazing effects in drylands. With a comparative approach we searched for plant functional types (PFTs) with a consistent response to grazing across two areas differing in climatic aridity, situated in South Africa's grassland and savanna biomes. We aggregated herbaceous species into PFTs, using hierarchical combinations of traits (from single- to three-trait PFTs). Traits relate to life history, growth form and leaf width. We first confirmed that soil and grazing gradients were largely independent from each other, and then searched in each biome for PFTs with a sensitive response to grazing, avoiding confounding with soil conditions. We found no response consistency, but biome-specific optimum aggregation levels. Three-trait PFTs (e.g. broad-leaved perennial grasses) and two-trait PFTs (e.g. perennial grasses) performed best as indicators of grazing effects in the semi-arid grassland and in the arid savanna biome, respectively. Some PFTs increased with grazing pressure in the grassland, but decreased in the savanna. We applied biome-specific grazing indicators to evaluate if differences in grazing management related to land tenure (communal versus freehold) had effects on vegetation. Tenure effects were small, which we mainly attributed to large variability in grazing pressure across farms. We conclude that the striking lack of generalizable PFT responses to grazing is due to a convergence of aridity and grazing effects, and unlikely to be overcome by more refined classification approaches. Hence, PFTs with an opposite response to grazing in the two biomes rather have a unimodal response along a gradient of additive forces of aridity and grazing. The study advocates for hierarchical trait combinations to identify localized indicator sets for grazing effects. Its methodological approach may also be useful for identifying ecological indicators in other ecosystems. PMID- 25111799 TI - Effects of aging on genioglossus motor units in humans. AB - The genioglossus is a major upper airway dilator muscle thought to be important in obstructive sleep apnea pathogenesis. Aging is a risk factor for obstructive sleep apnea although the mechanisms are unclear and the effects of aging on motor unit remodeled in the genioglossus remains unknown. To assess possible changes associated with aging we compared quantitative parameters related to motor unit potential morphology derived from EMG signals in a sample of older (n = 11; >55 years) versus younger (n = 29; <55 years) adults. All data were recorded during quiet breathing with the subjects awake. Diagnostic sleep studies (Apnea Hypopnea Index) confirmed the presence or absence of obstructive sleep apnea. Genioglossus EMG signals were analyzed offline by automated software (DQEMG), which estimated a MUP template from each extracted motor unit potential train (MUPT) for both the selective concentric needle and concentric needle macro (CNMACRO) recorded EMG signals. 2074 MUPTs from 40 subjects (mean+/-95% CI; older AHI 19.6+/-9.9 events/hr versus younger AHI 30.1+/-6.1 events/hr) were extracted. MUPs detected in older adults were 32% longer in duration (14.7+/-0.5 ms versus 11.1+/-0.2 ms; P = 0.05), with similar amplitudes (395.2+/-25.1 uV versus 394.6+/-13.7 uV). Amplitudes of CNMACRO MUPs detected in older adults were larger by 22% (62.7+/ 6.5 uV versus 51.3+/-3.0 uV; P<0.05), with areas 24% larger (160.6+/-18.6 uV.ms versus 130.0+/-7.4 uV.ms; P<0.05) than those detected in younger adults. These results confirm that remodeled motor units are present in the genioglossus muscle of individuals above 55 years, which may have implications for OSA pathogenesis and aging related upper airway collapsibility. PMID- 25111801 TI - Comparative 2D-DIGE proteomic analysis of bovine mammary epithelial cells during lactation reveals protein signatures for lactation persistency and milk yield. AB - Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-kappaB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling. PMID- 25111803 TI - Theory on the dynamics of oscillatory loops in the transcription factor networks. AB - We develop a detailed theoretical framework for various types of transcription factor gene oscillators. We further demonstrate that one can build genetic oscillators which are tunable and robust against perturbations in the critical control parameters by coupling two or more independent Goodwin-Griffith oscillators through either -OR- or -AND- type logic. Most of the coupled oscillators constructed in the literature so far seem to be of -OR- type. When there are transient perturbations in one of the -OR- type coupled-oscillators, then the overall period of the system remains constant (period-buffering) whereas in case of -AND- type coupling the overall period of the system moves towards the perturbed oscillator. Though there is a period-buffering, the amplitudes of oscillators coupled through -OR- type logic are more sensitive to perturbations in the parameters associated with the promoter state dynamics than -AND- type. Further analysis shows that the period of -AND- type coupled dual-feedback oscillators can be tuned without conceding on the amplitudes. Using these results we derive the basic design principles governing the robust and tunable synthetic gene oscillators without compromising on their amplitudes. PMID- 25111804 TI - A computational approach to evaluate the androgenic affinity of iprodione, procymidone, vinclozolin and their metabolites. AB - Our research is aimed at devising and assessing a computational approach to evaluate the affinity of endocrine active substances (EASs) and their metabolites towards the ligand binding domain (LBD) of the androgen receptor (AR) in three distantly related species: human, rat, and zebrafish. We computed the affinity for all the selected molecules following a computational approach based on molecular modelling and docking. Three different classes of molecules with well known endocrine activity (iprodione, procymidone, vinclozolin, and a selection of their metabolites) were evaluated. Our approach was demonstrated useful as the first step of chemical safety evaluation since ligand-target interaction is a necessary condition for exerting any biological effect. Moreover, a different sensitivity concerning AR LBD was computed for the tested species (rat being the least sensitive of the three). This evidence suggests that, in order not to over /under-estimate the risks connected with the use of a chemical entity, further in vitro and/or in vivo tests should be carried out only after an accurate evaluation of the most suitable cellular system or animal species. The introduction of in silico approaches to evaluate hazard can accelerate discovery and innovation with a lower economic effort than with a fully wet strategy. PMID- 25111805 TI - Responses of super rice (Oryza sativa L.) to different planting methods for grain yield and nitrogen-use efficiency in the single cropping season. AB - To break the yield ceiling of rice production, a super rice project was developed in 1996 to breed rice varieties with super high yield. A two-year experiment was conducted to evaluate yield and nitrogen (N)-use response of super rice to different planting methods in the single cropping season. A total of 17 rice varieties, including 13 super rice and four non-super checks (CK), were grown under three N levels [0 (N0), 150 (N150), and 225 (N225) kg ha-1] and two planting methods [transplanting (TP) and direct-seeding in wet conditions (WDS)]. Grain yield under WDS (7.69 t ha-1) was generally lower than TP (8.58 t ha-1). However, grain yield under different planting methods was affected by N rates as well as variety groups. In both years, there was no difference in grain yield between super and CK varieties at N150, irrespective of planting methods. However, grain yield difference was dramatic in japonica groups at N225, that is, there was an 11.3% and 14.1% average increase in super rice than in CK varieties in WDS and TP, respectively. This suggests that high N input contributes to narrowing the yield gap in super rice varieties, which also indicates that super rice was bred for high fertility conditions. In the japonica group, more N was accumulated in super rice than in CK at N225, but no difference was found between super and CK varieties at N0 and N150. Similar results were also found for N agronomic efficiency. The results suggest that super rice varieties have an advantage for N-use efficiency when high N is applied. The response of super rice was greater under TP than under WDS. The results suggest that the need to further improve agronomic and other management practices to achieve high yield and N-use efficiency for super rice varieties in WDS. PMID- 25111806 TI - Voice prosthetic biofilm formation and Candida morphogenic conversions in absence and presence of different bacterial strains and species on silicone-rubber. AB - Morphogenic conversion of Candida from a yeast to hyphal morphology plays a pivotal role in the pathogenicity of Candida species. Both Candida albicans and Candida tropicalis, in combination with a variety of different bacterial strains and species, appear in biofilms on silicone-rubber voice prostheses used in laryngectomized patients. Here we study biofilm formation on silicone-rubber by C. albicans or C. tropicalis in combination with different commensal bacterial strains and lactobacillus strains. In addition, hyphal formation in C. albicans and C. tropicalis, as stimulated by Rothia dentocariosa and lactobacilli was evaluated, as clinical studies outlined that these bacterial strains have opposite results on the clinical life-time of silicone-rubber voice prostheses. Biofilms were grown during eight days in a silicone-rubber tube, while passing the biofilms through episodes of nutritional feast and famine. Biofilms consisting of combinations of C. albicans and a bacterial strain comprised significantly less viable organisms than combinations comprising C. tropicalis. High percentages of Candida were found in biofilms grown in combination with lactobacilli. Interestingly, L. casei, with demonstrated favorable effects on the clinical life-time of voice prostheses, reduced the percentage hyphal formation in Candida biofilms as compared with Candida biofilms grown in absence of bacteria or grown in combination with R. dentocariosa, a bacterial strain whose presence is associated with short clinical life-times of voice prostheses. PMID- 25111808 TI - Solid support membrane-aerated catalytic biofilm reactor for the continuous synthesis of (S)-styrene oxide at gram scale. AB - Catalytic biofilms minimize reactant toxicity and maximize biocatalyst stability in selective transformations of chemicals to value-added products in continuous processes. The scaling up of such catalytic biofilm processes is challenging, due to fluidic and biological parameters affording a special reactor design affecting process performance. A solid support membrane-aerated biofilm reactor was optimized and scaled-up to yield gram amounts of (S)-styrene oxide, a toxic and instable high value chemical synthon. A sintered stainless steel membrane unit was identified as an optimal choice as biofilm substratum and for high oxygen mass transfer. A stable expanded polytetrafluoroethylene (ePTFE) membrane was best suited for in situ substrate delivery and product extraction. For the verification of scalability, catalytic biofilms of Pseudomonas sp. strain VLB120DeltaC produced (S)-styrene oxide to an average concentration of 390 mM in the organic phase per day (equivalent to 24.4 g Laq (-1) day(-1) ). This productivity was gained by efficiently using the catalyst with an excellent product yield on biomass of 13.6 gproduct gbiomass (-1) . This product yield on biomass is in the order of magnitude reported for other continuous systems based on artificially immobilized biocatalysts and is fulfilling the minimum requirements for industrial biocatalytic processes. Overall, 46 g of (S)-styrene oxide were produced and isolated (purity: 99%; enantiomeric excess [ee]: >99.8%. yield: 30%). The productivity is in a similar range as in comparable small-scale biofilm reactors highlighting the large potential of this methodology for continuous bioprocessing of bulk chemicals and biofuels. PMID- 25111809 TI - Anomalous one-electron processes in the chemistry of uranium nitrogen multiple bonds. AB - Novel reaction pathways are illustrated in the synthesis of uranium(IV), uranium(V), and uranium(VI) monoimido complexes. In contrast to the straightforward preparation of U(V)(?NSiMe3)[N(SiMe3)2]3 (1), the synthesis of a uranium(V) tritylimido complex, U(V)(?NCPh3)[N(SiMe3)2]3 (4), from U(III)[N(SiMe3)2]3 and Ph3CN3 was found to proceed through multiple one-electron steps. Whereas the oxidation of 1 with copper(II) salts produced the uranium(VI) monoimido complexes U(VI)(?NSiMe3)X[N(SiMe3)2]3 (X = Cl, Br), the reaction of 4 with CuBr2 undergoes sterically induced reduction to form the uranium(VI) monoimido complex U(VI)(?NCPh3)Br2[N(SiMe3)2]2, demonstrating a striking difference in reactivity based on imido substituent. The facile reduction of compounds 1 and 4 with KC8 allowed for the synthesis of the uranium(IV) monoimido derivatives, K[U(IV)(?NSiMe3)[N(SiMe3)2]3] (1-K) and K[U(IV)(?NCPh3)[N(SiMe3)2]3] (4-K), respectively. In contrast, an analogous uranium(IV) monoimido complex, K[U(IV)(?NPh(F))[N(SiMe3)Ph(F)]], Ph(F) = -pentafluorophenyl (6), was prepared through a loss of N(SiMe3)2Ph(F) concomitant with one-electron oxidation of a uranium(III) center. The uranium(IV) monoimido complexes were found to be reactive toward electrophiles, demonstrating N-C and N-Si single bond formation. One-electron reduction of nitrite provided a route to the uranium(VI) oxo/imido complex, [Ph4P][U(VI)O(?NSiMe3)[N(SiMe3)2]3]. The energetics and electrochemical processes involved in the various oxidation reactions are discussed. Finally, comparison of the U(VI)(?NSiMe3)X[N(SiMe3)2]3, X = Cl, Br, complexes with the previously reported U(VI)OX[N(SiMe3)2]3, X = Cl, Br, complexes suggested that the donor strength of the trimethylsilylimido ligand is comparable to the oxo ligand. PMID- 25111807 TI - An interferon response gene signature is associated with the therapeutic response of hepatitis C patients. AB - Infection with the hepatitis C virus (HCV) is a major cause of chronic liver diseases and hepatocellular carcinoma worldwide, and thus represents a significant public health problem. The type I interferon (IFN), IFNalpha, has been successful in treating HCV-infected patients, but current IFN-based treatment regimens for HCV have suboptimal efficacy, and relatively little is known about why IFN therapy eliminates the virus in some patients but not in others. Therefore, it is critical to understand the basic mechanisms that underlie the therapeutic resistance to IFN action in HCV-infected individuals, and there is an urgent need to identify those patients most likely to respond to IFN therapy for HCV. To characterize the response of HCV-infected patients to treatment with IFNalpha, the expression of an IFN-response gene signature comprised of IFN-stimulated genes and genes that play an important role in the innate immune response was examined in liver biopsies from HCV-infected patients enrolled in a clinical trial. In the present study we found that the expression of a subset of IFN-response genes was dysregulated in liver biopsy samples from nonresponsive hepatitis C patients as compared with virologic responders. Based on these findings, a statistical model was developed to help predict the response of patients to IFN therapy, and compared to results obtained to the IL28 mutation model, which is highly predictive of the response to IFN-based therapy in HCV infected patients. We found that a model incorporating gene expression data can improve predictions of IFN responsiveness compared to IL28 mutation status alone. PMID- 25111810 TI - Infiltration of CD8+ lymphocytes is an independent prognostic factor of biochemical failure-free survival in prostate cancer. AB - BACKGROUNDS: The adaptive immune system can potentially have dual roles in cancer development and progression by contributing to or suppressing tumor progression and metastasis. The aim of this study was to evaluate the prognostic impact of adaptive immune cells residing in different tumor compartments in prostate cancer. METHODS: Tissue microarrays from 535 patients were constructed from viable and representative tumor epithelial and stromal areas of primary PC tumors, as well as from normal epithelial and stromal areas. Immunohistochemistry was used to evaluate the density of CD3+, CD4+, CD8+, and CD20+ lymphocytes in both tumor epithelial and tumor stromal areas. RESULTS: In univariate analysis, a high density of CD3+ (P = 0.037) and CD8+ lymphocytes (P = 0.010) in tumor epithelial areas was associated with significantly shorter biochemical failure free survival. When analyzing both tumor epithelial and stromal tissue compartments as one entity, similar relationships were observed for CD3+ (P = 0.046), CD4+ (P = 0.026), and CD8+ (P = 0.003) lymphocytes. In multivariate analysis, high densities of CD8+ lymphocytes limited to tumor epithelial areas (HR = 1.45, P = 0.032), as well as in the total tumor tissue (HR = 1.57, P = 0.007), were independent negative prognostic factors for biochemical failure-free survival. CONCLUSIONS: A high density of CD8+ lymphocytes, especially in tumor epithelial areas, is an independent negative prognostic factor for biochemical failure-free survival. PMID- 25111811 TI - Formaldehyde and heavy metal migration from rubber and metallic packaging/utensils in Korea. AB - The aim of this study was to determine the non-intentionally added substances- formaldehyde and trace metals--at 4% acetic acid conditions in rubber and metallic packaging/utensils. The temperature effect on migration in rubber and metallic packaging/utensils was monitored at 60 degrees C and 100 degrees C under acidic (pH < 3) circumstances. The concentrations were: formaldehyde--23.1 MUg kg-1, lead--13.41 MUg kg-1, cadmium--0.15 MUg kg-1, total arsenic--2.02 MUg kg-1 and nickel--2.92 MUg kg-1 at 60 degrees C and formaldehyde--148.9 MUg kg-1, lead--17.04 MUg kg-1, cadmium--0.14 MUg kg-1, total arsenic--7.25 MUg kg-1 and nickel--8.7 MUg kg-1 at 100 degrees C. A significant difference was noticed in formaldehyde and total arsenic between both temperatures (p < 0.01), which was not present in other trace metals. In conclusion, formaldehyde and total arsenic were more sensitive with cooking temperature than the other metals. PMID- 25111812 TI - Genomic aspects of age-related macular degeneration. AB - Age-related macular degeneration (AMD) is a major late-onset posterior eye disease that causes central vision to deteriorate among elderly populations. The predominant lesion of AMD is the macula, at the interface between the outer retina and the inner choroid. Recent advances in genetics have revealed that inflammatory and angiogenic pathways play critical roles in the pathophysiology of AMD. Genome-wide association studies have identified ARMS2/HTRA1 and CFH as major AMD susceptibility genes. Genetic studies for AMD will contribute to the prevention of central vision loss, the development of new treatment, and the maintenance of quality of vision for productive aging. PMID- 25111813 TI - Microtubule stabilization attenuates vascular calcification through the inhibition of osteogenic signaling and matrix vesicle release. AB - Vascular calcification is a strong predictor of cardiovascular morbidity and mortality, especially in individuals with chronic kidney disease or diabetes. The mechanism of vascular calcification has remained unclear, however, and no effective therapy is currently available. Our study was aimed at identifying the role of dynamic remodeling of microtubule cytoskeletons in hyperphosphatemia induced vascular calcification. Exposure of primary cultures of mouse vascular smooth muscle cells (VSMCs) to inorganic phosphate (Pi) elicited ectopic calcification that was associated with changes in tubulin dynamics, induction of osteogenic signaling, and increased release of matrix vesicles. A microtubule depolymerizing agent enhanced Pi-dependent calcification, whereas microtubule stabilization by paclitaxel suppressed calcification both in VSMC cultures and in an ex vivo culture system for the mouse aorta. The inhibition of Pi-stimulated calcification by paclitaxel was associated with down-regulation of osteogenic signal and attenuation of matrix vesicle release. Our results indicate that microtubule plays a central role in vascular calcification, and that microtubule stabilization represents a potential new approach to the treatment of this condition. PMID- 25111814 TI - MicroRNA-665 is involved in the regulation of the expression of the cardioprotective cannabinoid receptor CB2 in patients with severe heart failure. AB - The myocardial endocannabinoid system has been linked to stress response and cardioprotection. In chronic heart failure (CHF), protective CB2 receptors are markedly up-regulated while CB1 receptors are slightly down-regulated. We here provide evidence that myocardial CB receptors are subject to microRNA regulation. By a combined computational and experimental approach we show that CB1 receptors are regulated by miR-494, and CB2 receptors are targeted by miR-665. Moreover, we demonstrate that in CHF, miR-665 expression is significantly decreased while miR 494 is slightly increased, which is concordant with the previously reported alterations of CB receptors. These results suggest that in CHF, altered expression of specific miRNAs may contribute to a compensatory response of the diseased myocardium. PMID- 25111815 TI - Detection of in vivo protein tyrosine nitration in petite mutant of Saccharomyces cerevisiae: consequence of its formation and significance. AB - Protein tyrosine nitration (PTN) is a selective post-translational modification often associated with physiological and pathophysiological conditions. Tyrosine is modified in the 3-position of the phenolic ring through the addition of a nitro group. In our previous study we first time showed that PTN occurs in vivo in Saccharomyces cerevisiae. In the present study we observed occurrence of PTN in petite mutant of S. cerevisiae which indicated that PTN is not absolutely dependent on functional mitochondria. Nitration of proteins in S. cerevisiae was also first time confirmed in immunohistochemical study using spheroplasts. Using proteosomal mutants Rpn10Delta, Pre9Delta, we first time showed that the fate of protein nitration in S. cerevisiae was not dependent on proteosomal clearing and probably played vital role in modulating signaling cascades. From our study it is evident that protein tyrosine nitration is a normal physiological event of S. cerevisiae. PMID- 25111816 TI - The role of calpain in an in vivo model of oxidative stress-induced retinal ganglion cell damage. AB - PURPOSE: In this study, we set out to establish an in vivo animal model of oxidative stress in the retinal ganglion cells (RGCs) and determine whether there is a link between oxidative stress in the RGCs and the activation of calpain, a major part of the apoptotic pathway. MATERIALS AND METHODS: Oxidative stress was induced in the RGCs of C57BL/6 mice by the intravitreal administration of 2,2' azobis (2-amidinopropane) dihydrochloride (AAPH, 30mM, 2MUl). Control eyes were injected with 2MUl of vehicle. Surviving Fluorogold (FG)-labeled RGCs were then counted in retinal flat mounts. Double staining with CellROX and Annexin V was performed to investigate the co-localization of free radical generation and apoptosis. An immunoblot assay was used both to indirectly evaluate calpain activation in the AAPH-treated eyes by confirming alpha-fodrin cleavage, and also to evaluate the effect of SNJ-1945 (a specific calpain inhibitor: 4% w/v, 100mg/kg, intraperitoneal administration) in these eyes. RESULTS: Intravitreal administration of AAPH led to a significant decrease in FG-labeled RGCs 7days after treatment (control: 3806.7+/-575.2RGCs/mm(2), AAPH: 3156.1+/ 371.2RGCs/mm(2), P<0.01). CellROX and Annexin V signals were co-localized in the FG-labeled RGCs 24h after AAPH injection. An immunoblot assay revealed a cleaved alpha-fodrin band that increased significantly 24h after AAPH administration. Intraperitoneally administered SNJ-1945 prevented the cleavage of alpha-fodrin and had a neuroprotective effect against AAPH-induced RGC death (AAPH: 3354.0+/ 226.9RGCs/mm(2), AAPH+SNJ-1945: 3717.1+/-614.6RGCs/mm(2), P<0.01). CONCLUSION: AAPH administration was an effective model of oxidative stress in the RGCs, showing that oxidative stress directly activated the calpain pathway and induced RGC death. Furthermore, inhibition of the calpain pathway protected the RGCs after AAPH administration. PMID- 25111817 TI - Genetic architecture of type 2 diabetes. AB - Genome-wide association studies (GWAS) have identified over 70 loci associated with type 2 diabetes (T2D). Most genetic variants associated with T2D are common variants with modest effects on T2D and are shared with major ancestry groups. To what extent the genetic component of T2D can be explained by common variants relies upon the shape of the genetic architecture of T2D. Fine mapping utilizing populations with different patterns of linkage disequilibrium and functional annotation derived from experiments in relevant tissues are mandatory to track down causal variants responsible for the pathogenesis of T2D. PMID- 25111818 TI - The role of mutation of metabolism-related genes in genomic hypermethylation. AB - Genetic mutations, metabolic dysfunction, and epigenetic misregulation are commonly considered to play distinct roles in tumor development and maintenance. However, intimate relationships between these mechanisms are now emerging. In particular, mutations in genes for the core metabolic enzymes IDH, SDH, and FH are significant drivers of diverse tumor types. In each case, the resultant accumulation of particular metabolites inhibits TET enzymes responsible for oxidizing 5-methylcytosine, leading to pervasive DNA hypermethylation. PMID- 25111819 TI - Evidence for participation of GCS1 in fertilization of the starlet sea anemone Nematostella vectensis: implication of a common mechanism of sperm-egg fusion in plants and animals. AB - It has been reported that GCS1 (Generative Cell Specific 1) is a transmembrane protein that is exclusively expressed in sperm cells and is essential for gamete fusion in flowering plants. The GCS1 gene is present not only in angiosperms but also in unicellular organisms and animals, implying the occurrence of a common or ancestral mechanism of GCS1-mediated gamete fusion. In order to elucidate the common mechanism, we investigated the role of GCS1 in animal fertilization using a sea anemone (Cnidaria), Nematostella vectensis. Although the existence of the GCS1 gene in N. vectensis has been reported, the expression of GCS1 in sperm and the role of GCS1 in fertilization are not known. In this study, we showed that the GCS1 gene is expressed in the testis and that GCS1 protein exists in sperm by in situ hybridization and proteomic analysis, respectively. Then we made four peptide antibodies against the N-terminal extracellular region of NvGCS1. These antibodies specifically reacted to NvGCS1 among sperm proteins on the basis of Western analysis and potently inhibited fertilization in a concentration dependent manner. These results indicate that sperm GCS1 plays a pivotal role in fertilization, most probably in sperm-egg fusion, in a starlet sea anemone, suggesting a common gamete-fusion mechanism shared by eukaryotic organisms. PMID- 25111820 TI - Skeletal analysis and differential gene expression in Runx2/Osterix double heterozygous embryos. AB - The transcription factors, Runx2 and Osterix (Osx), act downstream in the BMP2 pathway, and they are essential for osteoblast differentiation and bone formation. While Runx2 expression is normal in Osx-null mice, Osx is not expressed in Runx2-null mice, indicating that Osx acts downstream of Runx2 during bone formation. Runx2 and Osx are also independently regulated during bone formation. To define the unknown correlation between Runx2 and Osx in the regulation of bone formation, we analyzed the bone of Runx2/Osx double heterozygotes generated by mating heterozygous Runx2 and Osx mice and elucidated the differential gene expressions due to the lack of Runx2 and Osx in bone. Compared to the Runx2 and Osx heterozygous embryos, Runx2/Osx double heterozygous embryos showed reduced bone length in the humerus and femur as well as hypoplastic or complete absence of the maxillary and palatine shelf, presphenoid bone, zygomatic bone, and tympanic ring. Severe inward bending was observed in the ribs and humerus. Histological analysis showed an expanded region of hypertrophic chondrocytes and a reduced area of mineralized bones in the Runx2/Osx double heterozygous embryos. DNA microarray analysis of the calvaria of embryos allowed gene classification based on similarities in the upregulated and downregulated expression patterns. Clusters 1 and 2 include 68 downregulated genes and 18 upregulated genes, respectively, in the Runx2/Osx double heterozygous embryos. Finally, the skeletal analysis and gene expression profiles obtained by clustering may facilitate the understanding of the correlation between Runx2 and Osx in skeletal development. PMID- 25111821 TI - Somatic alterations and dysregulation of epigenetic modifiers in cancers. AB - Genomic discovery efforts in patients with cancer have been critical in identifying a recurrent theme of mutations in epigenetic modifiers. A number of novel and exciting basic biological findings have come from this work including the discovery of an enzymatic pathway for DNA cytosine demethylation, a link between cancer metabolism and epigenetics, and the critical importance of post translational modifications at specific histone residues in malignant transformation. Identification of cancer cell dependency on a number of these mutations has quickly resulted in the development of therapies targeting several of these genetic alterations. This includes, the development of mutant-selective IDH1 and IDH2 inhibitors, DOT1L inhibitors for MLL rearranged leukemias, EZH2 inhibitors for several cancer types, and the development of bromodomain inhibitors for many cancer types--all of which are in early phase clinical trials. In many cases, however, specific genetic targets linked to malignant transformation following mutations in individual epigenetic modifiers are not yet known. In this review we present functional evidence of how alterations in frequently mutated epigenetic modifiers promote malignant transformation and how these alterations are being targeted for cancer therapeutics. PMID- 25111822 TI - Separating heart and brain: on the reduction of physiological noise from multichannel functional near-infrared spectroscopy (fNIRS) signals. AB - OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) is an emerging technique for the in vivo assessment of functional activity of the cerebral cortex as well as in the field of brain-computer interface (BCI) research. A common challenge for the utilization of fNIRS in these areas is a stable and reliable investigation of the spatio-temporal hemodynamic patterns. However, the recorded patterns may be influenced and superimposed by signals generated from physiological processes, resulting in an inaccurate estimation of the cortical activity. Up to now only a few studies have investigated these influences, and still less has been attempted to remove/reduce these influences. The present study aims to gain insights into the reduction of physiological rhythms in hemodynamic signals (oxygenated hemoglobin (oxy-Hb), deoxygenated hemoglobin (deoxy-Hb)). APPROACH: We introduce the use of three different signal processing approaches (spatial filtering, a common average reference (CAR) method; independent component analysis (ICA); and transfer function (TF) models) to reduce the influence of respiratory and blood pressure (BP) rhythms on the hemodynamic responses. MAIN RESULTS: All approaches produce large reductions in BP and respiration influences on the oxy-Hb signals and, therefore, improve the contrast-to-noise ratio (CNR). In contrast, for deoxy-Hb signals CAR and ICA did not improve the CNR. However, for the TF approach, a CNR-improvement in deoxy-Hb can also be found. SIGNIFICANCE: The present study investigates the application of different signal processing approaches to reduce the influences of physiological rhythms on the hemodynamic responses. In addition to the identification of the best signal processing method, we also show the importance of noise reduction in fNIRS data. PMID- 25111823 TI - Identifying barriers to move to better health coverage: preferences for health insurance benefits among the rural poor population in La Guajira, Colombia. AB - Even though access to health insurance in Colombia has improved since the implementation of the 1993 health reforms (Law 100), universal coverage has not yet been accomplished. There is still a segment of the population under the low income (subsidized) health insurance policy or without health insurance altogether. The purpose of this research was to identify preferences and behavior regarding health insurance among the subsidized rural population in La Guajira, Colombia, and to understand why that population remains under the subsidized health insurance policy. The field experiment gathered information from 400 households regarding their socioeconomic situation, health conditions, and preferences for health insurance characteristics. Results suggest that the surveyed population gives priority to expanded family coverage, physician and hospital choice, and access to specialists, rather than to attributes associated with co-payments or premiums. That indicates that people value healthcare benefits and family coverage more than health insurance expenses, and policy makers could use these preferences to enroll subsidized population into the contributory regime. PMID- 25111824 TI - Odor tracking in sharks is reduced under future ocean acidification conditions. AB - Recent studies show that ocean acidification impairs sensory functions and alters the behavior of teleost fishes. If sharks and other elasmobranchs are similarly affected, this could have significant consequences for marine ecosystems globally. Here, we show that projected future CO2 levels impair odor tracking behavior of the smooth dogfish (Mustelus canis). Adult M. canis were held for 5 days in a current-day control (405 +/- 26 MUatm) and mid (741 +/- 22 MUatm) or high CO2 (1064 +/- 17 MUatm) treatments consistent with the projections for the year 2100 on a 'business as usual' scenario. Both control and mid CO2 -treated individuals maintained normal odor tracking behavior, whereas high CO2 -treated sharks significantly avoided the odor cues indicative of food. Control sharks spent >60% of their time in the water stream containing the food stimulus, but this value fell below 15% in high CO2 -treated sharks. In addition, sharks treated under mid and high CO2 conditions reduced attack behavior compared to the control individuals. Our findings show that shark feeding could be affected by changes in seawater chemistry projected for the end of this century. Understanding the effects of ocean acidification on critical behaviors, such as prey tracking in large predators, can help determine the potential impacts of future ocean acidification on ecosystem function. PMID- 25111826 TI - Balance of apoptotic cell death and survival in allergic diseases. AB - Allergic diseases result from over-reaction of the immune system in response to exogenous allergens, where inflammatory cells have constantly extended longevity and contribute to an on-going immune response in allergic tissues. Here, we review disequilibrium in the death and survival of epithelial cells and inflammatory cells in the pathological processes of asthma, atopic dermatitis, and other allergic diseases. PMID- 25111827 TI - The immune response of two microbial antigens delivered intradermally, sublingually, or the combination thereof. AB - A key consideration to produce a successful vaccine is the choice of appropriate vaccination route. Though most vaccines are administered parenterally, this route is not effective in producing a robust mucosal or cell-mediated response. Intradermal and sublingual vaccinations have been explored recently as potential needle-free immunization strategies. We explored intradermal and sublingual routes as well as the combination of the two routes in eliciting both systemic and mucosal immune responses. Mice were immunized intradermally or sublingually with dmLT, a mutant of Escherichia coli heat-labile toxin. A systemic IgG response is dominant in intradermal immunization while a mucosal IgA response is dominant in sublingual immunization. When routes were combined, a synergistic response was seen with high titers of anti-dmLT IgG and IgA. IpaB/IpaD antigens of Shigella flexneri type III secretion system, were admixed with dmLT as adjuvant and administered by each route alone or in combination. Again, the intradermal route elicited a systemic response while the sublingual route elicited a mucosal response. When combined, the routes produced a robust synergistic response to both antigens that exhibited a balanced Th1/Th2 response. These results provide a new potential needle-free immunization strategy that will benefit low income countries and increase compliance in industrial countries. PMID- 25111828 TI - Anti-Mullerian hormone is associated with extrauterine involvement and stage of disease in patients with endometrial cancer. AB - Our aim was to evaluate serum levels of anti-Mullerian hormone (AMH) and also immunohistochemical (IHC) staining properties of AMH receptor type II (AMHRII) in patients with endometrial cancer (EC) and a control group. Preoperatively, serum levels of AMH were assessed and AMHRII expression was evaluated by immunohistochemistry in a benign and malignant group. AMH serum levels of the control group and EC patients were comparable. For EC patients, there was no difference with respect to the AMH levels and tumour stage; grade; histological type; deep myometrial invasion; lymphovascular space invasion or lymph node involvement. However, AMH levels in patients with extrauterine involvement were higher than patients with disease confined to the uterus. EC samples were more likely to be stained positive for AMHRII than benign lesions. Also, as the stage of the lesion worsens, the rate of IHC staining of AMHRII decreases. In conclusion, AMHRII is expressed in normal endometrial cells as well as endometrial cancer cells. AMH levels increase in EC, with extrauterine involvement at least in locally advanced disease. Also AMH expression decreases as the disease is staged-up. PMID- 25111829 TI - Connecting carbon nanotubes to polyoxometalate clusters for engineering high performance anode materials. AB - Carbon nanotubes (CNTs) possess excellent structural and electronic properties and have been widely investigated as anode materials. Polyoxometalates (POMs) exhibit superior physical properties such as electronic versatility, redox characteristics and unique molecular structures. In this paper, we report the covalent modification of carbon nanotubes (CNTs) with organosilica-containing polyoxometalate (POM) of [Bu4N]4[SiW11O39{O(SiCH2CH2CH2NH2.HCl)2}] (SiW11-NH2) that leads to the formation of the nanocomposite material of CNTs-SiW11, which has been characterized by FT-IR, XRD, HR-TEM, XPS and Raman spectrum, etc. At a current density of 0.5 mA cm(-2), the application of CNTs-SiW11 nanocomposite as anode material in lithium batteries exhibits the first discharge capacity of 1189 mA h g(-1), and the second discharge capacity of 650 mA h g(-1), which remains stable up to 100 cycles. The CNTs-SiW11 nanocomposite exhibits high discharge capacity, good capacity retention and cycling stability. PMID- 25111830 TI - Effect of surface potential on extracellular matrix protein adsorption. AB - Extracellular matrix (ECM) proteins, such as fibronectin, laminin, and collagen IV, play important roles in many cellular behaviors, including cell adhesion and spreading. Understanding their adsorption behavior on surfaces with different natures is helpful for studying the cellular responses to environments. By tailoring the chemical composition in binary acidic (anionic) and basic (cationic) functionalized self-assembled monolayer (SAM)-modified gold substrates, variable surface potentials can be generated. To examine how surface potential affects the interaction between ECM proteins and substrates, a quartz crystal microbalance with dissipation detection (QCM-D) was used. To study the interaction under physiological conditions, the ionic strength and pH were controlled using phosphate-buffered saline at 37 degrees C, and the zeta potentials of the SAM-modified Au and protein were determined using an electrokinetic analyzer and phase analysis light scattering, respectively. During adsorption processes, the shifts in resonant frequency (f) and energy dissipation (D) were acquired simultaneously, and the weight change was calculated using the Kelvin-Voigt model. The results reveal that slightly charged protein can be adsorbed on a highly charged SAM, even where both surfaces are negatively charged. This behavior is attributed to the highly charged SAM, which polarizes the protein microscopically, and the Debye interaction, as well as other short range interactions such as steric force, hydrogen bonding, direct bonding, charged domains within the protein structure, etc., that allow adsorption, although the macroscopic electrostatic interaction discourages adsorption. For surfaces with a moderate potential, proteins are not significantly polarized by the surface, and the interaction can be predicted through simple electrostatic attraction. Furthermore, surface-induced self-assembly of protein molecules also affects the adsorbed structures and kinetics. The adsorbed layer properties, such as rigidity and packing behaviors, were further investigated using the D-f plot and phase detection microscopy (PDM) imaging. PMID- 25111831 TI - Valuation, categories and attributes. AB - Existing research on categories has only examined indirectly the value associated with being a member of a category relative to the value of the set of attributes that determine membership in that category. This study uses survey data to analyze consumers' preferences for the "organic" label versus for the attributes underlying that label. We found that consumers generally preferred products with the category label to those with the attributes required for the organic label but without the label. We also found that the value accorded to the organic label increased with the number of attributes that an individual associated with the category. Category membership nevertheless still had greater value than even that of the sum of the attributes associated with it. PMID- 25111832 TI - Vitamin D status among Thai school children and the association with 1,25 Dihydroxyvitamin D and parathyroid hormone levels. AB - In several low latitude countries, vitamin D deficiency is emerging as a public health issue. Adequate vitamin D is essential for bone health in rapidly growing children. In the Thai population, little is known about serum 25-hydroxyvitamin D [25(OH)D] status of infants and children. Moreover, the association between 25(OH)D and the biological active form of 1,25-dihydroxyvitamin D [1,25(OH)]2D is not clear. The specific aims of this study were to characterize circulating serum 25(OH)D, 1,25(OH)2D and their determinants including parathyroid hormone (PTH), age, sex, height and body mass index (BMI) in 529 school-aged Thai children aged 6-14 y. Adjusted linear regression analysis was performed to examine the impact of age and BMI, and its interaction with sex, on serum 25(OH)D concentrations and 1,25(OH)2D concentrations. Serum 25(OH)D, 1,25(OH)2D and PTH concentrations (geometric mean +/- geometric SD) were 72.7+/-1.2 nmol/L, 199.1+/-1.3 pmol/L and 35.0+/-1.5 ng/L, respectively. Only 4% (21 of 529) participants had a serum 25(OH)D level below 50 nmol/L. There was statistically significant evidence for an interaction between sex and age with regard to 25(OH)D concentrations. Specifically, 25(OH)D concentrations were 19% higher in males. Moreover, females experienced a statistically significant 4% decline in serum 25(OH)D levels for each increasing year of age (P = 0.001); no decline was seen in male participants with increasing age (P = 0.93). When BMI, age, sex, height and serum 25(OH)D were individually regressed on 1,25(OH)2D, height and sex were associated with 1,25(OH)2D with females exhibiting statistically significantly higher serum 1,25(OH)2D levels compared with males (P<0.001). Serum 1,25(OH)2D among our sample of children exhibiting fairly sufficient vitamin D status were higher than previous reports suggesting an adaptive mechanism to maximize calcium absorption. PMID- 25111833 TI - Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi. AB - Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD , IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naive B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans. PMID- 25111835 TI - Completed suicide with violent and non-violent methods in rural Shandong, China: a psychological autopsy study. AB - BACKGROUND: This study aims to describe the specific characteristics of completed suicides by violent methods and non-violent methods in rural Chinese population, and to explore the related factors for corresponding methods. METHODS: Data of this study came from investigation of 199 completed suicide cases and their paired controls of rural areas in three different counties in Shandong, China, by interviewing one informant of each subject using the method of Psychological Autopsy (PA). RESULTS: There were 78 (39.2%) suicides with violent methods and 121 (60.8%) suicides with non-violent methods. Ingesting pesticides, as a non violent method, appeared to be the most common suicide method (103, 51.8%). Hanging (73 cases, 36.7%) and drowning (5 cases, 2.5%) were the only violent methods observed. Storage of pesticides at home and higher suicide intent score were significantly associated with choice of violent methods while committing suicide. Risk factors related to suicide death included negative life events and hopelessness. CONCLUSIONS: Suicide with violent methods has different factors from suicide with non-violent methods. Suicide methods should be considered in suicide prevention and intervention strategies. PMID- 25111836 TI - Ultrathin hexagonal hybrid nanosheets synthesized by graphene oxide-assisted exfoliation of beta-Co(OH)2 mesocrystals. AB - In the present study, we report the synthesis of a high-quality, single-crystal hexagonal beta-Co(OH)2 nanosheet, exhibiting a thickness down to ten atomic layers and an aspect ratio exceeding 900, by using graphene oxide (GO) as an exfoliant of beta-Co(OH)2 nanoflowers. Unlike conventional approaches using ionic precursors in which morphological control is realized by structure-directing molecules, the beta-Co(OH)2 flower-like superstructures were first grown by a nanoparticle-mediated crystallization process, which results in large 3D superstructure consisting of ultrathin nanosheets interspaced by polydimethoxyaniline (PDMA). Thereafter, beta-Co(OH)2 nanoflowers were chemically exfoliated by surface-active GO under hydrothermal conditions into unilamellar single-crystal nanosheets. In this reaction, GO acts as a two-dimensional (2D) amphiphile to facilitate the exfoliation process through tailored interactions between organic and inorganic molecules. Meanwhile, the on-site conjugation of GO and Co(OH)2 promotes the thermodynamic stability of freestanding ultrathin nanosheets and restrains further growth through Oswald ripening. The unique 2D structure combined with functionalities of the hybrid ultrathin Co(OH)2 nanosheets on rGO resulted in a remarkably enhanced lithium-ion storage performance as anode materials, maintaining a reversible capacity of 860 mA h g( 1) for as many as 30 cycles. Since mesocrystals are ubiquitous and rich in morphological diversity, the strategy of the GO-assisted exfoliation of mesocrystals developed here provides an opportunity for the synthesis of new functional nanostructures that could bear importance in clean renewable energy, catalysis, photoelectronics, and photonics. PMID- 25111834 TI - Prevalence of HPV 16 and HPV 18 lineages in Galicia, Spain. AB - Genetic variants of human papillomavirus types 16 and 18 (HPV16/18) could differ in their cancer risk. We studied the prevalence and association with high-grade cervical lesions of different HPV16/18 variant lineages in a case-control study including 217 cases (cervical intraepithelial neoplasia grade 2 or grade 3 or worse: CIN2 or CIN3+) and 116 controls (no CIN2 or CIN3+ in two-year follow-up). HPV lineages were determined by sequencing the long control region (LCR) and the E6 gene. Phylogenetic analysis of HPV16 confirmed that isolates clustered into previously described lineages: A (260, 87.5%), B (4, 1.3%), C (8, 2.7%), and D (25, 8.4%). Lineage D/lineage A strains were, respectively, detected in 4/82 control patients, 19/126 CIN3+ cases (OR = 3.1, 95%CI: 1.0-12.9, p = 0.04), 6/1 glandular high-grade lesions (OR = 123, 95%CI: 9.7-5713.6, p<0.0001), and 4/5 invasive lesions (OR = 16.4, 95%CI: 2.2-113.7, p = 0.002). HPV18 clustered in lineages A (32, 88.9%) and B (4, 11.1%). Lineage B/lineage A strains were respectively detected in 1/23 control patients and 2/5 CIN3+ cases (OR = 9.2, 95%CI: 0.4-565.4, p = 0.12). In conclusion, lineages A of HPV16/18 were predominant in Spain. Lineage D of HPV16 was associated with increased risk for CIN3+, glandular high-grade lesions, and invasive lesions compared with lineage A. Lineage B of HPV18 may be associated with increased risk for CIN3+ compared with lineage A, but the association was not significant. Large well-designed studies are needed before the application of HPV lineage detection in clinical settings. PMID- 25111838 TI - Nanomechanical properties, SEM, and EDS microanalysis of dentin treated with 2.5% titanium tetrafluoride, before and after an erosive challenge. AB - The aim was to assess the nanohardness (H) and the reduced modulus of elasticity (Er ) of 2.5% titanium tetrafluoride (TiF4 ) modified dentin, before and after an erosive challenge with 0.3% citric acid (CA). Exposed dentin surfaces were divided into two groups (n = 5): (1) Control-no dentin pretreatment with TiF4 prior to etching with CA, and (2) Experimental-dentin pretreatment with TiF4 + CA. The H and the Er of intertubular dentin were measured using a triboindenter at different time points: baseline for both groups, after using 2.5% TiF4 for the experimental group, and after using CA for both the experimental and the control groups. Scanning electron microscope and energy dispersive X-ray spectroscopy (EDS) analysis of the dentin surfaces were undertaken at the same time points for both groups. Two-way ANOVA for randomized block design was applied. There was significant interaction between the application of the TiF4 solution and different time points (p = 0.001 for H and p < 0.001 for Er ), identified by Tukey's test. Erosive challenge provided a significant decrease in H and Er mean values. The TiF4 solution caused a significant increase in H and Er values, but no significant differences were found between post-TiF4 and post-CA application. TiF4 application produced a precipitate surface layer on intertubular and intratubular dentin. EDS analysis indicated the presence of titanium. The H and Er of the dentin surface were greatly increased after application of 2.5% TiF4 . TiF4 may modify the micromorphology of the dentin surface and produces an erosive resistance surface. PMID- 25111839 TI - Intermolecular interactions and 3D structure in cellulose-NaOH-urea aqueous system. AB - The dissolution of cellulose in NaOH/urea aqueous solution at low temperature is a key finding in cellulose science and technology. In this paper, (15)N and (23)Na NMR experiments were carried out to clarify the intermolecular interactions in cellulose/NaOH/urea aqueous solution. It was found that there are direct interactions between OH(-) anions and amino groups of urea through hydrogen bonds and no direct interaction between urea and cellulose. Moreover, Na(+) ions can interact with both cellulose and urea in an aqueous system. These interactions lead to the formation of cellulose-NaOH-urea-H2O inclusion complexes (ICs). (23)Na relaxation results confirmed that the formation of urea-OH(-) clusters can effectively enhance the stability of Na(+) ions that attracted to cellulose chains. Low temperature can enhance the hydrogen bonding interaction between OH(-) ions and urea and improve the binding ability of the NaOH/urea/H2O clusters that attached to cellulose chains. Cryo-TEM observation confirmed the formation of cellulose-NaOH-urea-H2O ICs, which is in extended conformation with mean diameter of about 3.6 nm and mean length of about 300 nm. Possible 3D structure of the ICs was proposed by the M06-2X/6-31+G(d) theoretical calculation, revealing the O3H...O5 intramolecular hydrogen bonds could remain in the ICs. This work clarified the interactions in cellulose/NaOH/urea aqueous solution and the 3D structure of the cellulose chain in dilute cellulose/NaOH/urea aqueous solution. PMID- 25111841 TI - Self-reported versus administrative identification of American Indian and Alaska Native arrestees: effects on relative estimates of illicit drug use and alcohol abuse. AB - Arrestee Drug Abuse Monitoring program data were used to consider the effects of two methods of racial classification upon estimates of illicit drug use and alcohol abuse among American Indian/Alaska Native (AI/AN) arrestees. Overall, compared to arrestees who self-identified as Black, White, Asian/Pacific Islander, or Hispanic, arrestees self-identifying as AI/AN were most likely to be identified administratively as something other than AI/AN. Results of 'difference of difference' analyses indicate that differences in estimates of AI/AN versus non-AI/AN arrestees' illicit drug use and alcohol abuse were much more extreme when identification was based on administrative records than when based upon arrestees' self-reports. PMID- 25111840 TI - Land-bridge calibration of molecular clocks and the post-glacial Colonization of Scandinavia by the Eurasian field vole Microtus agrestis. AB - Phylogeography interprets molecular genetic variation in a spatial and temporal context. Molecular clocks are frequently used to calibrate phylogeographic analyses, however there is mounting evidence that molecular rates decay over the relevant timescales. It is therefore essential that an appropriate rate is determined, consistent with the temporal scale of the specific analysis. This can be achieved by using temporally spaced data such as ancient DNA or by relating the divergence of lineages directly to contemporaneous external events of known time. Here we calibrate a Eurasian field vole (Microtus agrestis) mitochondrial genealogy from the well-established series of post-glacial geophysical changes that led to the formation of the Baltic Sea and the separation of the Scandinavian peninsula from the central European mainland. The field vole exhibits the common phylogeographic pattern of Scandinavian colonization from both the north and the south, however the southernmost of the two relevant lineages appears to have originated in situ on the Scandinavian peninsula, or possibly in the adjacent island of Zealand, around the close of the Younger Dryas. The mitochondrial substitution rate and the timescale for the genealogy are closely consistent with those obtained with a previous calibration, based on the separation of the British Isles from mainland Europe. However the result here is arguably more certain, given the level of confidence that can be placed in one of the central assumptions of the calibration, that field voles could not survive the last glaciation of the southern part of the Scandinavian peninsula. Furthermore, the similarity between the molecular clock rate estimated here and those obtained by sampling heterochronous (ancient) DNA (including that of a congeneric species) suggest that there is little disparity between the measured genetic divergence and the population divergence that is implicit in our land bridge calibration. PMID- 25111842 TI - Health perceptions among urban American Indians with type II diabetes. AB - Since the 1940s, American Indians (AIs) have increasingly urbanized, moving off of reservations in large part due to federal policies of tribal termination and relocation. Though previous AI research has largely focused on reservation associated challenges, many of these same challenges persist among urban AI populations. One mutual concern is the growing prevalence and incidence of type II diabetes mellitus (T2DM). While behavioral, genetic, and socioeconomic determinants of T2DM have been explored, much less is known about the influence of cultural and psychosocial factors. Recent studies suggest that the way AIs perceive diabetes may affect their health trajectory and explain their poor prognosis. Through the use of the Illness Perception Questionnaire, we explored this hypothesis in a pilot study of urban AI with T2DM living in Los Angeles County. We found that the majority of participants have a neutral perception about their diabetes: They view their condition to be long lasting yet treatable and indicate reasonable understanding of its symptoms and progression. We also identified "personal control," the level of perceived control one has over his or her disease, as a strong correlate of overall illness perception and, thus, a potentially useful psychological metric. PMID- 25111843 TI - Client and provider views on access to care for substance-using American Indians: perspectives from a Northern Plains urban clinic. AB - In addition to disparities in rates of substance use problems, American Indians (AIs) report multiple barriers to receiving treatment services. The present study utilized intake questionnaire data and focus groups to gain perspectives from 152 clients (65% male, 35% female; mean age 30 years) and 6 female providers on access to treatment for Northern Plains AIs in an urban, non-Native program. AI clients acknowledged the need for treatment more often than did substance users in general, but faced greater resource barriers. Both clients and providers offered specific recommendations for improving access to substance use treatment for AI populations in the Northern Plains. PMID- 25111844 TI - The economics of vaccination. AB - The market for vaccinations is widely believed to be characterized by market failures, because individuals do not internalize the positive externalities that their vaccination decisions may confer on other individuals. Francis (1997) provided a set of assumptions under which the equilibrium vaccination pattern is socially optimal. We show that his conditions are not necessary for the welfare theorem to hold but that in general, the market yields inefficiently low vaccination uptake. Equilibrium non-optimality may obtain if (i) agents can recover from infection, (ii) vaccines are imperfect, (iii) individuals are ex ante heterogeneous, (iv) vaccination timing is inflexible or (v) the planning horizon is finite. Apart from the case with heterogeneity, inefficiencies result from the presence of strategic interaction. PMID- 25111845 TI - On-line monitoring of chemical reactions by using bench-top nuclear magnetic resonance spectroscopy. AB - Real-time nuclear magnetic resonance (NMR) spectroscopy measurements carried out with a bench-top system installed next to the reactor inside the fume hood of the chemistry laboratory are presented. To test the system for on-line monitoring, a transfer hydrogenation reaction was studied by continuously pumping the reaction mixture from the reactor to the magnet and back in a closed loop. In addition to improving the time resolution provided by standard sampling methods, the use of such a flow setup eliminates the need for sample preparation. Owing to the progress in terms of field homogeneity and sensitivity now available with compact NMR spectrometers, small molecules dissolved at concentrations on the order of 1 mmol L(-1) can be characterized in single-scan measurements with 1 Hz resolution. Owing to the reduced field strength of compact low-field systems compared to that of conventional high-field magnets, the overlap in the spectrum of different NMR signals is a typical situation. The data processing required to obtain concentrations in the presence of signal overlap are discussed in detail, methods such as plain integration and line-fitting approaches are compared, and the accuracy of each method is determined. The kinetic rates measured for different catalytic concentrations show good agreement with those obtained with gas chromatography as a reference analytical method. Finally, as the measurements are performed under continuous flow conditions, the experimental setup and the flow parameters are optimized to maximize time resolution and signal-to-noise ratio. PMID- 25111847 TI - Clearing up cardiorenal confusion. PMID- 25111846 TI - Advanced glycation end products increase carbohydrate responsive element binding protein expression and promote cancer cell proliferation. AB - Diabetic patients have increased levels of advanced glycation end products (AGEs) and the role of AGEs in regulating cancer cell proliferation is unclear. Here, we found that treating colorectal and liver cancer cells with AGEs promoted cell proliferation. AGEs stimulated both the expression and activation of a key transcription factor called carbohydrate responsive element binding protein (ChREBP) which had been shown to promote glycolytic and anabolic activity as well as proliferation of colorectal and liver cancer cells. Using siRNAs or the antagonistic antibody for the receptor for advanced glycation end-products (RAGE) blocked AGEs-induced ChREBP expression or cell proliferation in cancer cells. Suppressing ChREBP expression severely impaired AGEs-induced cancer cell proliferation. Taken together, these results demonstrate that AGEs-RAGE signaling enhances cancer cell proliferation in which AGEs-mediated ChREBP induction plays an important role. These findings may provide new explanation for increased cancer progression in diabetic patients. PMID- 25111848 TI - Kinetic study of the OH radical reaction with phenylacetylene. AB - The reaction of the OH radical with phenylacetylene is studied over the 298-423 K temperature range and 1-7.5 Torr pressure range in a quasi-static reaction cell. The OH radical is generated by 266 nm photolysis of hydrogen peroxide (H2O2) or 355 nm photolysis of nitrous acid (HONO), and its concentration monitored using laser-induced fluorescence. The measured reaction rates are found to strongly depend on laser fluence at 266 nm. The 266 nm absorption cross-section of phenylacetylene is measured to be 1.29 (+/-0.71) * 10(-17) cm(2), prohibiting any accurate kinetic measurements at this wavelength. The rates are independent of laser fluence at 355 nm with an average value of 8.75 (+/-0.73) * 10(-11) cm(3) s(-1). The reaction exhibits no pressure or temperature dependence over the studied experimental conditions and is much faster than the estimated values presently used in combustion models. These results are consistent with the formation of a short lifetime intermediate that stabilizes by collisional quenching with the buffer gas. The structures of the most likely formed products are discussed based on both the computed energies for the OH-addition intermediates and previous theoretical investigations on similar chemical systems. PMID- 25111849 TI - Intriguing transmission electron microscopy images observed for perpendicularly oriented cylindrical microdomains of block copolymers. AB - Intriguing images of dislocation structures were observed by the transmission electron microscopy (TEM) technique for hexagonally packed cylindrical microdomains in a block copolymer (polystyrene-block-polyethylenebutylene-block polystyrene triblock copolymer) film. The polystyrene (PS) cylinders were embedded in the polyethylenebutylene (PEB) matrix and oriented perpendicular to the surface of the thin section for the TEM observations. In order to understand such strange dislocation structures, we applied an image processing technique using two-dimensional Fourier transform (FT) and inverse Fourier transform (IFT) methods. It was found that these intriguing images were not ascribed to real dislocation structures but were fake ones due to the moire effect caused by the overlapping of hexagons with a slightly mismatched orientation. Furthermore, grain boundaries in the ultrathin section can be identified by image processing using FT and IFT methods. PMID- 25111850 TI - Electrophysiology-based detection of emergency braking intention in real-world driving. AB - OBJECTIVE: The fact that all human action is preceded by brain processes partially observable through neuroimaging devices such as electroencephalography (EEG) is currently being explored in a number of applications. A recent study by Haufe et al (2011 J. Neural Eng. 8 056001) demonstrates the possibility of performing fast detection of forced emergency brakings during driving based on EEG and electromyography, and discusses the use of such neurotechnology for braking assistance systems. Since the study was conducted in a driving simulator, its significance regarding real-world applicability needs to be assessed. APPROACH: Here, we replicate that experimental paradigm in a real car on a non public test track. MAIN RESULTS: Our results resemble those of the simulator study, both qualitatively (in terms of the neurophysiological phenomena observed and utilized) and quantitatively (in terms of the predictive improvement achievable using electrophysiology in addition to behavioral measures). Moreover, our findings are robust with respect to a temporary secondary auditory task mimicking verbal input from a fellow passenger. SIGNIFICANCE: Our study serves as a real-world verification of the feasibility of electrophysiology-based detection of emergency braking intention as proposed in Haufe et al (2011 J. Neural Eng. 8 056001). PMID- 25111851 TI - Gonadotropin-releasing hormone agonist selectively augments thymopoiesis and prevents cell apoptosis in LPS induced thymic atrophy model independent of gonadal steroids. AB - Lipopolysaccharide (LPS) causes acute thymic atrophy, a phenomenon that has been linked to immune dysfunction and poor survival during sepsis. The systemic response to LPS involves a rise in glucocorticoids and proinflammatory cytokines which contribute greatly to thymic involution and apoptosis. Gonadotropin releasing hormone (GnRH) analog exerts thymopoietic regulatory effects and possesses immunostimulant properties. We determined whether leuprolide, a GnRH analog can be useful in LPS induced thymic involution and apoptosis. Mice injected with 100 MUg of LPS intraperitoneally led to involution of thymus, to decrease of CD4(+)8(+) thymocyte subset, and to fragmentation of thymic DNA. Leuprolide (100 MUg/mouse, s.c.) pretreatment significantly attenuated LPS induced thymic atrophy, and also reduced LPS induced systemic rise in corticosterone levels. The observed effect of leuprolide remained unaffected in castrated and ovariectomized mice. Collectively, leuprolide has protective action independent of gonadal steroids, which was mediated by blunting of the systemic corticosteroid response in LPS induced thymic atrophy model. PMID- 25111852 TI - Glucagon like peptide-1 attenuates bleomycin-induced pulmonary fibrosis, involving the inactivation of NF-kappaB in mice. AB - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality and poor prognosis. Previous studies confirmed that NF-kappaB plays a critical role in the pathogenesis of pulmonary fibrosis and glucagon like peptide 1 (GLP-1) has a property of anti-inflammation by inactivation of NF-kappaB. Furthermore, the GLP-1 receptor was detected in the lung tissues. Our aim was to investigate the potential value and mechanisms of GLP-1 on BLM-induced pulmonary fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with or without GLP-1 administration. 28 days after BLM infusion, the number of total cells, macrophages, neutrophils, lymphocytes, and the content of TGF-beta1 in BALF were measured. Hematoxylin-eosin (HE) staining and Masson's trichrome (MT) staining were performed. The Ashcroft score and hydroxyproline content were analyzed. RT-qPCR and western blot were used to evaluate the expression of alpha SMA and VCAM-1. The phosphorylation of NF-kappaB p65 was also assessed by western blot. DNA binding of NF-kappaB p65 was measured through Trans(AM) p65 transcription factor ELISA kit. GLP-1 reduced inflammatory cell infiltration and the content of TGF-beta1 in BLAF in mice with BLM injection. The Ashcroft score and hydroxyproline content were decreased by GLP-1 administration. Meanwhile, BLM induced overexpression of alpha-SMA and VCAM-1 were blocked by GLP-1 treatment in mice. GLP-1 also reduced the ratio of phosphor-NF-kappaB p65/total-NF-kappaB p65 and NF-kappaB p65 DNA binding activity in BLM-induced pulmonary fibrosis in mice. Our data found that BLM-induced lung inflammation and pulmonary fibrosis were significantly alleviated by GLP-1 treatment in mice, possibly through inactivation of NF-kappaB. PMID- 25111854 TI - Think twice before prescribing custom-compounded bioidentical hormone therapy. PMID- 25111853 TI - Tristetraprolin is involved in the glucocorticoid-mediated interleukin 8 repression. AB - Glucocorticoids have been widely used in various inflammatory disorders, and the transcriptional repression of inflammatory mediators has been considered to be the main mechanism of action. However, a previous study showed that dexamethasone inhibited interleukin 8 (IL-8) expression by promoting IL-8 mRNA decay, which implies a posttranscriptional regulation. Nevertheless, by which mechanism dexamethasone destabilized IL-8 mRNA was unclear. Another study indicated that an RNA-binding protein, tristetraprolin (TTP), could be induced by dexamethasone. TTP can bind to AU-rich elements (ARE) in the 3'-untranslated region of target mRNAs and promotes mRNA degradation. So, we speculated that dexamethasone destabilized IL-8 mRNA by upregulating TTP expression. Here, we report that dexamethasone reduced IL-8 expression through destabilizing IL-8 mRNA in human pulmonary microvascular endothelial cells (HPMECs). Dexamethasone stimulation increased TTP mRNA and protein levels. TTP silencing led to mRNA stabilization and protein upregulation of IL-8. These results provide the evidence that the glucocorticoid, in HPMECs, inhibits IL-8 expression through TTP at the posttranscriptional level. PMID- 25111855 TI - Toward a better understanding of the relationship between vulvodynia and chronic stressors. PMID- 25111856 TI - Risks and effectiveness of compounded bioidentical hormone therapy: a case series. AB - After the publication of the Women's Health Initiative, attitudes towards management of menopausal symptoms changed dramatically. One alternative that has received much media attention is the use of bioidentical hormone therapy (BHT). The media and celebrity endorsements have promoted a number of misconceptions about the risks and benefits associated with the various forms of BHT. This article will review the available evidence regarding the safety and efficacy of BHT in comparison to conventional hormone therapy. We will also review several cases seen in our midlife women's referral clinics, which demonstrate concerns for the safety and efficacy of BHT, including unexplained endometrial cancer in otherwise healthy BHT users. Due to the lack of sufficient data to support the efficacy or safety of BHT, we recommend the use of United States Food and Drug Administration-approved regimens in the management of menopausal symptoms. PMID- 25111857 TI - Ex vivo protective effects of nicotinamide and 3-aminobenzamide on rat synaptosomes treated with Abeta(1-42). AB - Alzheimer's disease (AD) is the most common form of dementia and is characterized by the presence of senile plaques and neurofibrillary tangles, along with synaptic loss. The underlying mechanisms of AD are not clarified yet, but oxidative stress and mitochondrial dysfunction are important factors. Overactivation of poly(adenosine diphosphate ribose) polymerase-1 (PARP-1) enzyme has been known to cause neuroinflammation and cell death in neurodegenerative processes. The aim of the present study was to investigate the protective effects of the PARP-1 inhibitors, 3-aminobenzamide (3-AB) and nicotinamide (NA), against amyloid beta peptide (1-42) (Abeta(1-42))-induced oxidative damage and mitochondrial reduction capacity on isolated synaptosomes. Rats were injected intraperitoneally with 3-AB (30-100 mg kg(-1)), NA (100-500 mg kg(-1)) or with saline for 7 days. Synaptosomes were incubated with 10-30 MUM Abeta(1-42) or saline for 6 h at 37 degrees C. Ex vivo Abeta(1-42) treatment significantly induced oxidative stress and mitochondrial dysfunction in synaptosomes of the saline group, while synaptosomes of 3-AB and NA groups showed significant decreases in lipid peroxidation, reactive oxygen species production and protein oxidation. Moreover, both NA and 3-AB were able to improve the mitochondrial reduction capacity against Abeta(1-42). These data suggest that NA and 3-AB may have protective effects in neurodegenerative processes because of the reduced levels of oxidative stress and the improvement of mitochondrial function. PMID- 25111858 TI - The hypertriglyceridemia is associated with isolated impaired glucose tolerance in subjects without insulin resistance. AB - AIM OF THE STUDY: The objective of this study was to determine if hypertriglyceridemia is associated with isolated impaired glucose tolerance in subjects without insulin resistance. MATERIALS AND METHODS: A total of 365 apparently healthy individuals aged 20-65 years were enrolled in a population based cross-sectional study. Subjects were allocated into the groups with and without hypertriglyceridemia. Age, gender, body mass index, and waist circumference were matched criteria. Individuals with impaired fasting glucose, impaired fasting glucose+impaired glucose tolerance, diabetes, homeostasis model assessment of insulin resistance index >= 2.5, and/or chronic illnesses such as renal disease or malignancy were excluded. Hypertriglyceridemia was defined by triglycerides levels >= 150 mg/dL. Impaired glucose tolerance was defined by plasma glucose concentration 2-h post-load glucose >= 140 mg/dL <200 mg/dL. Subjects with impaired glucose tolerance were required to have fasting plasma glucose levels <100 mg/dL. Logistic regression analysis was used to compute the odds ratio between hypertriglyceridemia (independent variable) and impaired glucose tolerance (dependent variable). RESULTS: A total of 132 and 233 subjects were allocated into the groups with and without hypertriglyceridemia, respectively. The frequency of impaired glucose tolerance was 13.6% and 5.6% in the individuals with and without hypertriglyceridemia, p = 0.01. The logistic regression analysis adjusted by gender, blood pressure, and high-density lipoprotein cholesterol showed that hypertriglyceridemia is significantly associated with impaired glucose tolerance (OR 2.34; 95% CI: 1.02-5.32, p = 0.04). CONCLUSION: Results of this study indicate that hypertriglyceridemia is independently associated with isolated impaired glucose tolerance in subjects without insulin resistance. PMID- 25111859 TI - Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: a systematic review. AB - Cisplatin/gemcitabine association has been a standard of care for first-line regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine regimen is frequently preferred. Because comparative effectiveness in clinical outcomes of cisplatin- versus oxaliplatin-containing chemotherapy is not available, a systematic review of studies assessing cisplatin/gemcitabine or oxaliplatin/gemcitabine chemotherapies in advanced biliary tract cancer was performed. Published studies evaluating cisplatin/gemcitabine or oxaliplatin/gemcitabine in advanced biliary tract cancer were included. Each study was weighted according to the number of patients included. The primary objective was to assess weighted median of medians overall survival (mOS) reported for both regimens. Secondary goals were to assess weighted median of medians progression-free survival (mPFS) and toxic effects were pooled and compared within each arm. Thirty-three studies involving 1470 patients were analyzed. In total, 771 and 699 patients were treated by cisplatin/gemcitabine and oxaliplatin/gemcitabine, respectively. Weighted median of mOS was 9.7 months in cisplatin group and 9.5 months in oxaliplatin group. Cisplatin-based chemotherapy was significantly associated with more grade 3 and 4 asthenia, diarrhea, liver toxicity, and hematological toxicity. Sensitivity analysis including only the studies with the standard regimen of cisplatin (25-35 mg/m(2) administered on days 1 and 8) showed that the weighted median of mOS increased from 9.7 to 11.7 months but Gem/CDDP regimen remained more toxic than Gemox regimen. These results suggest that the Gem/CDDP regimen with cisplatin (25-35 mg/m(2)) administered on days 1 and 8 is associated with survival advantage than Gemox regimen but with addition of toxicity. PMID- 25111860 TI - Alkali-soluble polysaccharide, isolated from Lentinus edodes, induces apoptosis and G2/M cell cycle arrest in H22 cells through microtubule depolymerization. AB - The aim of the study was to evaluate the pro-apoptotic effects of polysaccharides derived from Lentinus edodes and further elucidated the mechanisms of this action. Our results demonstrated that marked morphological changes of apoptosis were observed after treatment of L. edodes polysaccharides [Lentinan (LTN)]. Moreover, LTN-induced cell apoptosis was characterized by a rapid stimulation of reactive oxygen species production, the loss of mitochondrial membrane potential and an increase in intracellular concentration of Ca(2+) . In addition, the results of the haematoxylin and eosin and TUNEL assay further confirmed that LTN induced apoptosis in vivo. Furthermore, flow cytometry analysis showed that LTN could arrest the cell cycle at G2/M phase, and immunofluorescence showed LTN caused disruption of microtubule. These results suggest that disruption of cellular microtubule network, arrest of the cell cycle at G2/M phase and induction of apoptosis may be one of the possible mechanisms of anti-tumour effect of LTN. PMID- 25111861 TI - The Yes-associated protein controls the cell density regulation of Hedgehog signaling. AB - The evolutionarily conserved Hedgehog (Hh) signaling pathway is essential for correct embryogenesis and is misregulated in several malignancies. In cell culture, Hh-sensitive cells display a striking dependence on cell density with active Hh signaling requiring cell-to-cell contact. As the Hippo/YAP system is tightly linked to cell density control and contact inhibition, we investigated the cross-talk between the two pathways. Our data reveal that the suppression of Hh signaling in the absence of cellular contacts is independent of primary cilia and is mediated by the YAP oncogene. Overexpression of YAP blocks Hh signaling whereas RNA interference-mediated knockdown of YAP enhances Hh/GLI activity. Despite this negative regulation, Hh signaling promotes YAP activity through post transcriptional mechanisms, resulting in a negative feedback loop. In vivo, we found strong nuclear YAP immunoreactivity restricted to compartments with low Hh pathway activity in human and mouse pancreatic cancer. Finally, we identified protease-activated receptors (PARs) as molecules being able to override the inverse Hippo/Hh regulation, potentially giving tumors a mechanism to utilize both oncogenic pathways in parallel.Oncogenesis (2014) 3, e112; doi:10.1038/oncsis.2014.27; published online 11 August 2014. PMID- 25111862 TI - Selective repression of the oncogene cyclin D1 by the tumor suppressor miR-206 in cancers. AB - MicroRNAs (miRNAs) are deregulated in cancer and have been shown to exhibit both oncogenic and tumor suppressive functions. Although the functional effects of several miRNAs have been elucidated, those of many remain to be discovered. In silico analysis identified microRNA-206 (miR-206) binding sites in the 3' untranslated regions (3'-UTR) of both the mouse and human CCND1 gene. Cyclin D1 is a recognized oncogene involved in direct phosphorylation of the retinoblastoma (Rb) protein and promoting cell cycle transition from G1 to S. miR-206 specifically binds to the CCND1 3'-UTR and mediates reduction of both cyclin D1 protein and mRNA. Expression of miR-206 induced a G1 arrest and a decrease in cell proliferation in breast cancer cells. Ectopic expression of miRNA-resistant cyclin D1 was able to reverse the miR-206-induced decrease in cell proliferation. Therefore, we identified miR-206 as an activator of cell cycle arrest resulting in a decrease in cell proliferation that is dependent on the inhibition of cyclin D1. Interestingly, prostatic cancer (PCa) cells express low levels of miR-206 resulting in deregulated cyclin D1 expression compared with non-transformed primary prostatic epithelial cells (PrEC). Finally, we demonstrate that cyclin D1 is regulated by miR-206 in PrEC but not in PCa cells and this is due to the absence of a CCND1 3'-UTR in these cells. This suggests that miR-206-based anti cyclin D1 targeted therapy would be beneficial in cancers where cyclin D1 is overexpressed and contains a 3'-UTR. PMID- 25111864 TI - Anatomy. The oldest child of Mother Medicine. PMID- 25111863 TI - PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft growth through NF-kappaB. AB - Prostate-specific G-protein-coupled receptor (PSGR), a member of the olfactory subfamily of G-protein-coupled receptors, is specifically expressed in human prostate tissue and overexpressed in prostate cancer (PCa). This expression pattern suggests a possible role in PCa initiation and progression. We developed a PSGR transgenic mouse model driven by a probasin promoter and investigated the role of PSGR in prostate malignancy. Overexpression of PSGR induced a chronic inflammatory response that ultimately gave rise to premalignant mouse prostate intraepithelial neoplasia lesions in later stages of life. PSGR-overexpressing LnCaP cells in prostate xenografts formed larger tumors compared with normal LnCaP cancer cells, suggesting a role of PSGR in the promotion of tumor development. Furthermore, we identified nuclear factor-kappaB (NF-kappaB) or RELA as a key downstream target activated by PSGR signaling. We also show that this regulation was mediated in part by the phosphatidylinositol-3-kinase/Akt (PI3K/AKT) pathway, highlighting a collaborative role between PI3K/AKT and NF kappaB during tumor inflammation downstream of PSGR in the initial phases of prostate disease.Oncogenesis (2014) 3, e114; doi:10.1038/oncsis.2014.29; published online 11 August 2014. PMID- 25111866 TI - The role of ghrelin in metabolic regulation. AB - PURPOSE OF REVIEW: To discuss recent research on the role of ghrelin in the regulation of carbohydrate and lipid metabolism in the context of its wider role in regulating energy balance. RECENT FINDINGS: Ghrelin possesses a range of centrally and peripherally mediated metabolic actions influencing insulin glucose homeostasis and fatty acid metabolism and appetite. Although acyl ghrelin was previously thought to be the active hormone, recent evidence suggests that des acyl ghrelin also possesses activity, and the enzyme ghrelin-O-acyl transferase regulates their interconversion. In partnership with insulin and leptin, ghrelin defends against energy deficit by enhancing hunger, conserving carbohydrate and promoting fat oxidation. In the postprandial state, it contributes to satiety, energy storage and favours glucose oxidation. New research suggests a range of new roles including addictive behaviours, cardiovascular protection, neuroprotection and regeneration and perhaps the ageing process. SUMMARY: Ghrelin functions primarily as a short-term metabolic switch at the onset of fasting, gearing the fuel economy away from glucose uptake, conserving glucose for vital functions, favouring fatty acid oxidation and triggering food-seeking behaviour. The ghrelin system is a potential target for a range of pharmacological interventions, but its pleiotropic nature makes selective treatments challenging. PMID- 25111867 TI - The energy balance in cancer cachexia revisited. AB - PURPOSE OF REVIEW: To review new putative mechanisms involved in the pathophysiology of a disturbed energy balance in cancer cachexia, which can lead to novel targets for clinical cachexia management. In the context of rapid developments in tumour treatment with potential systemic consequences, this article reviews recent data on energy requirements. Furthermore, we focus on new insights in brown adipose tissue (BAT) activity and reward processing in the brain in relation to the cachexia process. RECENT FINDINGS: Nearly no new data have been published on energy requirements of cancer patients in the light of comprehensive new therapies in oncology. New developments, such as the introduction of staging with 18F-fluorodeoxyglucose PET-computed tomography scanning, led to the observation that BAT activation may contribute to impaired energy balance in cancer cachexia. Animal and human data to date provide an indication that BAT activation indeed occurs, but its quantitative impact on the degree of cachexia is controversial. The peripheral and central nervous system is known to influence satiation, with a possible role for impaired food reward processing in the brain. To date, there are limited confirmatory data, but this is an interesting new area to explore for better understanding and treating cancer-induced anorexia. SUMMARY: The multimodal approach to counteract cancer cachexia should expand its targets to BAT and food reward processing in the brain. PMID- 25111868 TI - Integration of genome-wide of Stat3 binding and epigenetic modification mapping with transcriptome reveals novel Stat3 target genes in glioma cells. AB - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many human tumors, including gliomas, and regulates the expression of genes implicated in proliferation, survival, apoptosis, angiogenesis and immune regulation. Only a small fraction of those genes has been proven to be direct STAT3 targets. In gliomas, STAT3 can play tumor suppressive or oncogenic roles depending on the tumor genetic background with target genes being largely unknown. RESULTS: We used chromatin immunoprecipitation, promoter microarrays and deep sequencing to assess the genome-wide occupancy of phospho (p)-Stat3 and epigenetic modifications of H3K4me3 and H3ac in C6 glioma cells. This combined assessment identified a list of 1200 genes whose promoters have both Stat3 binding sites and epigenetic marks characteristic for actively transcribed genes. The Stat3 and histone markings data were also intersected with a set of microarray data from C6 glioma cells after inhibition of Jak2/Stat3 signaling. Subsequently, we found 284 genes characterized by p-Stat3 occupancy, activating histone marks and transcriptional changes. Novel genes were screened for their potential involvement in oncogenesis, and the most interesting hits were verified by ChIP-PCR and STAT3 knockdown in human glioma cells. CONCLUSIONS: Non-random association between silent genes, histone marks and p-Stat3 binding near transcription start sites was observed, consistent with its repressive role in transcriptional regulation of target genes in glioma cells with specific genetic background. PMID- 25111869 TI - Breaking away from the norm: a new perspective on cancer therapeutics. PMID- 25111870 TI - Formal [3+3] cycloaddition of indol-2-yl carbinol with azadiene and the oxidative ring expansion reaction for the synthesis of indole azepinones. AB - We present the unprecedented reaction of a [3+3] cyclization of indol-2-yl carbinol with azadiene for the construction of a six-membered ring and the subsequent oxidative ring expansion reaction for the construction of indole azepinones. PMID- 25111871 TI - Improved hydrogen production in the microbial electrolysis cell by inhibiting methanogenesis using ultraviolet irradiation. AB - Methanogenesis inhibition is essential for the improvement of hydrogen (H2) yield and energy recovery in the microbial electrolysis cell (MEC). In this study, ultraviolet (UV) irradiation was proposed as an efficient method for methanogenesis control in a single chamber MEC. With 30 cycles of operation with UV irradiation in the MEC, high H2 concentrations (>91%) were maintained, while without UV irradiation, CH4 concentrations increased significantly and reached up to 94%. In the MEC, H2 yields ranged from 2.87 +/- 0.03 to 3.70 +/- 0.11 mol H2/mol acetate with UV irradiation and from 3.78 +/- 0.12 to 0.03 +/- 0.004 mol H2/mol acetate without UV irradiation. Average energy efficiencies from the UV irradiated MEC were 1.5 times of those without UV irradiation. Energy production from the MEC without UV irradiation was a negative energy yield process because of large amount of CH4 produced over time, which was mainly attributable to cathodic hydrogenotrophic methanogenesis. Our results clearly showed that UV irradiation could effectively inhibit methanogenesis and improve MEC performance to produce H2. PMID- 25111872 TI - Rhodium-catalyzed [(3+2)+1] carbocyclization reactions of alkynylidenecyclopropanes with carbon monoxide: regiospecific construction of polysubstituted phenols. AB - The development of the rhodium-catalyzed [(3+2)+1] carbocyclization reaction of alkynylidenecyclopropanes with carbon monoxide to construct polysubstituted phenols is described. This work offers a convenient method for the selective formation of tetra- and pentasubstituted phenols, which provide important intermediates for target directed synthesis. Finally, the ability to regiospecifically functionalize the phenols using conventional methods further illustrates the utility of this process. PMID- 25111873 TI - Is Gadolinium contrast enhancement necessary in screening MRI for asymmetric sensorineural hearing loss? PMID- 25111874 TI - The longer you stay, the worse your health? A critical review of the negative acculturation theory among Asian immigrants. AB - Researchers have become increasingly interested in the health patterns of immigrants with longer residence in the United States, as this reveals the health consequences of integration processes. The negative acculturation effect has been the dominant interpretation of duration patterns, despite empirical and theoretical uncertainties about this assumption. This theory assumes that immigrant health declines with longer residence in the United States because of poorer health behaviors and health risks that reflect Americanized lifestyles. This paper reviews the empirical support for the negative acculturation theory among Asian immigrants to determine if and when it is an appropriate interpretation for duration patterns. I conclude that empirical inconsistencies and methodological issues limit the negative acculturation theory as the primary interpretation for duration patterns. First, there is no consistent evidence that health behaviors decline with time. There is also substantial group heterogeneity in duration patterns as well as heterogeneity across health outcomes. The literature has not adequately addressed methodological shortcomings, such as confounding by cohort effects or non-linear duration patterns. Length of residence in the United States is still an important aspect of Asian immigrant health, but the mechanisms of this relationship are still understudied. I propose alternative frameworks between duration and health that consider environmental influences and end with future research directions to explore research gaps. PMID- 25111875 TI - Factors associated with no dental treatment in preschoolers with toothache: a cross-sectional study in outpatient public emergency services. AB - Many parents rely on emergency services to deal with their children's dental problems, mostly pain and infection associated with dental caries. This cross sectional study analyzed the factors associated with not doing an oral procedure in preschoolers with toothache attending public dental emergency services. Data were obtained from the clinical files of preschoolers treated at all nine dental emergency centers in Goiania, Brazil, in 2011. Data were children's age and sex, involved teeth, oral procedures, radiography request, medications prescribed and referrals. A total of 531 files of children under 6 years old with toothache out of 1,108 examined were selected. Children's mean age was 4.1 (SD 1.0) years (range 1-5 years) and 51.6% were girls. No oral procedures were performed in 49.2% of cases; in the other 50.8%, most of the oral procedures reported were endodontic intervention and temporary restorations. Primary molars were involved in 48.4% of cases. With the exception of "sex", the independent variables tested in the regression analysis significantly associated with non-performance of oral procedures: age (OR 0.7; 95% CI 0.5-0.8), radiography request (OR 3.8; 95% CI 1.7 8.2), medication prescribed (OR 7.5; 95% CI 4.9-11.5) and patient referred to another service (OR 5.7; 3.0-10.9). Many children with toothache received no oral procedure for pain relief. PMID- 25111876 TI - Study of epigenetic properties of Poly(HexaMethylene Biguanide) hydrochloride (PHMB). AB - Poly(HexaMethylene Biguanide) hydrochloride (PHMB) CAS No. [32289-58-0] is a particularly effective member of the biguanides antiseptic chemical group, and has been in use since the early fifties in numerous applications. It has been proposed that PHMB be classified as a category 3 carcinogen although PHMB is not genotoxic. It has been hypothesized that PHMB may have epigenetic properties effects, including non-genotoxic modifications of DNA bases, DNA methylation and mitogenic cytokine production. These properties have been assessed in vitro using 3 cell types: Caco-2 cells (from a human colon adenocarcinoma) with a non functional p53 gene. (?p53: mut p53), N2-A (Neuro-2A cells, mouse neural cells), the brain being a possible target organ in rodents and HepG2 cells (human hepatocellular carcinoma) with functional p53 gene. From the concentration 1 ug/mL up to 20 ug/mL of PHMB, no effect was observed, either growth stimulation or inhibition. Viability testing using neutral red led to an IC 50 of 20-25 ug/mL after treatment with PHMB for 3 h, whereas the MTT test led to IC50 values of 80 ug/mL, 160 ug/mL and 160 ug/mL respectively for HepG2 cells, Neuro-2A cells and Caco-2 cells. PHMB does not induce significant oxidative stress (production of MDA or lipoperoxidation, nor does it induce hydroxylation of DNA (8-OH-dG) and/or its hypermethylation (m5dC), the latter being strongly implicated in DNA replication and regulation and cell division. PHMB does not induce significant production of mitogenic cytokines such as TNF-alpha (tumor necrosis factor), interleukins (IL-1 alpha), and the transcription factor nuclear factor kappa B (NF-kappaB) which can cause either apoptosis or stimulate the growth of transformed cells or tumors. Instead, from concentrations of 20 to 100 ug/mL, PHMB kills cells of all types in less than 3 h. The expression of genes involved in the mechanisms of cell death induced by PHMB, including p53, the pro apoptotic gene bax and others, the anti-apoptotic bcl-2 and caspase-3 has been evaluated by RT-PCR. Finally, the status of GAP-junctions (GJIC) in the presence of PHMB has been determined and appeared to not be significantly affected. Taken together the data show that in vitro PHMB does not exhibit clear and remarkable epigenetic properties except a slight increase of some cytokines and transcription factor at higher concentrations at which cell lysis occurs rapidly. PMID- 25111877 TI - Physical activity and the perceived neighbourhood environment - looking at the association the other way around. AB - The association between physical activity (PA) and variables of the perceived environment mainly originate from cross-sectional studies that introduced the idea that the environment influences the PA level of residents. However, the direction of cause and effect has not been solved with finality. The aim of this study was to investigate whether residents' perception of their proximate environment differs depending on their level of PA in transport and recreation. We conducted a cross-sectional survey with residents of six different parts of the city of Cologne, Germany. The sample of 470 adults (52.8% females; mean age = 35.5 +/- 13.8 years) filled in the Global Physical Activity Questionnaire (GPAQ), as well as the European Environmental Questionnaire ALPHA. To distinguish between residents with "low" and "high" PA, we split the samples into two on the basis of the specific median in transport- and recreation-related PA. In the "high" vs. "low" PA group of the overall sample, we noted 4%-16% more "PA favourable" environmental perceptions in seven of the 15 environmental variables. Multiple linear regression analyses were performed to investigate associations of socio demographic correlates and transport- and recreation-related PA on the dependent variables of the environmental perception. In this case, levels of PA were significant predictors for eight of the 15 items concerning environmental perceptions. Thus, the present study introduces the idea that residents with higher levels of transport and recreational PA may perceive their environment in a more "PA-favourable" way than residents with lower levels. PMID- 25111878 TI - Atopic diseases and systemic lupus erythematosus: an epidemiological study of the risks and correlations. AB - Both atopic diseases and systemic lupus erythematosus (SLE) are immune disorders that may lead to physical complications or multi-system comorbidities. This population-based case-control study was designed to evaluate the risk of SLE associated with atopic diseases. Using a national insurance claims dataset in Taiwan, we identified 1673 patients newly diagnosed with SLE and 6692 randomly selected controls frequency matched for gender, age and index date. The odds ratios (OR) for SLE were calculated for associations with allergic rhinitis, allergic conjunctivitis, atopic dermatitis and asthma. The SLE patients were predominantly female (82.5%) with a mean age of 40.1 (SD = 18.2). The patients with SLE had a higher rate of atopic dermatitis (6.81% vs. 3.06%), and asthma (10.6% vs. 7.64%) was approximately 2 times more common in the patients with lupus than in those without. The patients with atopic disease (atopic dermatitis, allergic rhinitis, allergic conjunctivitis and asthma) were at a significant risk for SLE. The overall risk for SLE increased as the number of atopic diseases increased from 1.46 to 2.29, compared with-individuals without the diseases (p < 0.0001). In conclusion, this population-based case-control study demonstrates a significant relationship between atopic diseases and the risk of SLE, especially for females. Atopic dermatitis plays a stronger role than other types of atopic disease in association with SLE. PMID- 25111879 TI - In-vitro indicators of natural resistance and milk-producing ability in dairy buffaloes (Bubalus bubalis). AB - The aim of this study was to explore the possibility of detecting novel phenotypes of natural resistance at the molecular level through the in-vitro stimulation of monocyte-derived macrophages (MDMs). This study was conducted with 16 healthy buffaloes who were reared for milk production and for whom data on milk-producing ability were available for several lactations. MDMs from circulating monocytes were activated with interferon-gamma and lipopolysaccharide. The response was evaluated using Western blotting to detect the presence of 2 types of proteins separated by electrophoresis: tyrosine phosphorylated proteins, which are indicators of the dynamic control of biochemical pathways, and IkB-alpha (Kappa light polipeptide gene enhancer in B cells Inhibitor, alpha) protein, which controls the activity of nuclear factor kappa-light-chain-enhancer of activated B cells-a transcription factor that is responsible for the expression of proinflammatory cytokines. The results showed that the buffaloes who were positive for IkB-alpha proteins had a significantly higher milk-producing ability than the buffaloes who did not express IkB-alpha. On the contrary, no significant difference was detected between the high and low milk-producing buffaloes with regard to the presence of tyrosine-phosphorylated proteins. This preliminary study indicated that it may be possible to identify the more disease-resistant nonhuman animals on a molecular level. The results, therefore, indicate that an intense selection toward the increase of milk yield could impair natural disease resistance in future dairy buffalo generations. PMID- 25111881 TI - Warm thanks: gratitude expression facilitates social affiliation in new relationships via perceived warmth. AB - Recent theorizing on the nature and function of gratitude (the find-remind-and bind theory; Algoe, 2012) stipulates that expressing gratitude should serve to alert previously unacquainted peers to the potential for a high-quality social bond (i.e., a find function). Although the logic of this premise is supported by extant research, it has not, as yet, been tested empirically. In the current study, participants received a note from a previously unacquainted peer that contained an expression of gratitude (or did not) with regard to prior benefits provided by the participant. After providing ratings of the peer and ostensibly completing the study, participants were given an opportunity to spontaneously give their contact information to the peer, which served as a behavioral measure of affiliation. In line with the proposed find function of gratitude expressions, recipients of expressions of gratitude were more likely to extend the effort to continue the relationship with the novel peer by providing that peer with a means to contact them. This experiment also provided evidence that perceptions of interpersonal warmth (e.g., friendliness, thoughtfulness) serve as the mechanism via which gratitude expressions facilitate affiliation: insofar as gratitude expressions signaled interpersonal warmth of the expresser, they prompted investment in the burgeoning social bond. As such, these findings provide the first empirical evidence regarding 1 of the 3 central premises of the find-remind and-bind theory of gratitude (Algoe, 2012) in the context of novel relationships. PMID- 25111882 TI - Naturally-occurring expressive suppression in daily life depletes executive functioning. AB - The depleting impact of experimentally manipulated expressive suppression (ES) on cognition (especially executive functioning and related processes) has been well established (Baumeister, 2002a). However, the impact of ES that occurs naturally in the course of daily life has not been examined. Sixty two adults (M = 22.89 years old) completed questions about recent ES burden (over the past 2 weeks and on the test day) and completed cognitive measures assessing executive functioning, working memory, and speed of information processing. Individuals with higher-than-usual burden of ES on the test day exhibited poorer executive performance and those with high ES over the past 2 weeks exhibited poorer processing speed above and beyond depression, suggesting that ES burden as it occurs in the course of daily life is associated with compromised cognitive performance. PMID- 25111880 TI - Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid. AB - IMPORTANCE: Studies have shown that bisphosphonates may have antitumor and antimetastatic properties. Recently, observational studies have suggested a possible protective effect of bisphosphonates on breast cancer, but the effect of bisphosphonate use on risk of breast cancer has not been tested in randomized trials. OBJECTIVE: To assess the relationship of postmenopausal breast cancer incidence and bisphosphonate use using data from 2 randomized (1:1), double blind, placebo-controlled trials. DESIGN, SETTING, AND PARTICIPANTS: The Fracture Intervention Trial (FIT) randomly assigned 6459 women aged 55 to 81 years to alendronate or placebo for a mean follow-up of 3.8 years. The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned 7765 women aged 65 to 89 years to annual intravenous zoledronic acid or placebo for a mean follow-up of 2.8 years. Data were collected at clinical centers in the United States (FIT and HORIZON-PFT) and in Asia and the Pacific, Europe, North America, and South America (HORIZON-PFT). Women, in either study, with recurrent breast cancer or who reported a history of breast cancer were excluded from analyses. In each trial, a blinded review was conducted of each cancer adverse event report to verify incident invasive breast cancer cases. The primary analysis compared events in the active vs placebo group using a log-rank test. INTERVENTION: Alendronate vs placebo (FIT) or zoledronic acid vs placebo (HORIZON-PFT). MAIN OUTCOMES AND MEASURES: Hazard ratio for incident breast cancer in the bisphosphonate treatment group compared to the placebo group. RESULTS: There was no significant difference in the rate of breast cancer in FIT: 1.5% (n = 46) in the placebo group and 1.8% (n = 57) in the alendronate group (hazard ratio [HR], 1.24 [95% CI, 0.84-1.83]). In HORIZON-PFT, there was also no significant difference: 0.8% (n = 29) in the placebo group and 0.9% (n = 33) in the zoledronic acid group (HR, 1.15 [95% CI, 0.70-1.89]). There was also no significant difference when the data from FIT and HORIZON-PFT were pooled (HR, 1.20 [95% CI, 0.89-1.63]). CONCLUSIONS AND RELEVANCE: These 2 randomized clinical trials do not support the findings from observational research. Contrary to the results from observational studies, we found that 3 to 4 years of bisphosphonate treatment did not decrease the risk of invasive postmenopausal breast cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00049829 (HORIZON-PFT). PMID- 25111883 TI - Dissecting the global variation of gene expression for the functional interpretation of transcriptome data. AB - To perform their biological functions, individual genes exhibit varying ranges of expression levels. Thus, considering the intrinsic variability of gene expression can improve geneset-based functional analyses which are typically used to interpret transcriptome data. Through the extensive quantitative analysis of the expressional variability of individual genes using large collections of transcriptome and proteome data, we found the existence of the intrinsic variability of gene expression at the transcriptional level. Interestingly, genes under post-translational regulation were not sensitively regulated at the transcriptional level. Because genes have intrinsically different levels of regulation at the transcription and translation stages, the functional geneset based interpretation of transcriptome data should only include genes that are significantly varied at the transcriptional level. Thus, by removing genes with low transcriptional variation from the DNA microarray data, we showed that geneset enrichment analysis could provide improved resolution in prioritizing target functional pathways in several different experimental datasets. PMID- 25111884 TI - Role of post-operative radiation boost for soft tissue sarcomas with positive margins following pre-operative radiation and surgery. AB - BACKGROUND AND OBJECTIVES: The role of a radiation therapy (RT) boost for positive margins following pre-operative RT and surgery in extremity soft tissue sarcomas (STS) is unclear. We assessed the contribution of a boost to local control (LC), disease-free survival (DFS), and overall survival (OS). METHODS: We identified 67 patients treated from 1987 to 2011 with pre-operative RT and surgery with positive margin(s). Select patients received a boost delivered as peri-operative Iridium-192 brachytherapy (BRT), intra-operative electrons (IORT), or post-operative external beam RT (EBRT). RESULTS: Ten patients received no RT boost, 10 received a BRT or IORT boost, and 47 received an EBRT boost. Five-year LC rates for no boost, BRT/IORT boost, and EBRT boost were 100%, 78%, and 71% (P = 0.5). On multivariate analysis, there were no significant predictors for LC. Variables associated with improved DFS rates were single positive margin (P = 0.007) and low tumor grade (P = 0.03). Tumor size <5 cm (P = 0.003), low grade (P = 0.001), and boost (P = 0.02) were associated with longer survival. CONCLUSIONS: We did not identify a LC advantage for an RT boost. Given the unidentified selection factors for delivery of boost and its potential toxicities, its role in this setting remains unproven. PMID- 25111885 TI - Sensitive diagnosis of cutaneous leishmaniasis by lesion swab sampling coupled to qPCR. AB - Variation in clinical accuracy of molecular diagnostic methods for cutaneous leishmaniasis (CL) is commonly observed depending on the sample source, the method of DNA recovery and the molecular test. Few attempts have been made to compare these variables. Two swab and aspirate samples from lesions of patients with suspected CL (n = 105) were evaluated alongside standard diagnosis by microscopic detection of amastigotes or culture of parasites from lesion material. Three DNA extraction methods were compared: Qiagen on swab and aspirate specimens, Isohelix on swabs and Boil/Spin of lesion aspirates. Recovery of Leishmania DNA was evaluated for each sample type by real-time polymerase chain reaction detection of parasitic 18S rDNA, and the diagnostic accuracy of the molecular method determined. Swab sampling combined with Qiagen DNA extraction was the most efficient recovery method for Leishmania DNA, and was the most sensitive (98%; 95% CI: 91-100%) and specific (84%; 95% CI: 64-95%) approach. Aspirated material was less sensitive at 80% (95% CI: 70-88%) and 61% (95% CI: 50 72%) when coupled to Qiagen or Boil-Spin DNA extraction, respectively. Swab sampling of lesions was painless, simple to perform and coupled with standardized DNA extraction enhances the feasibility of molecular diagnosis of CL. PMID- 25111886 TI - Impact of long-term erythrocytapheresis on growth and peak height velocity of children with sickle cell disease. AB - BACKGROUND: Children with sickle cell disease (SCD) lag in weight and height and have a delayed growth spurt compared to normal children. We studied the effect of long-term erythrocytapheresis (LTE) on the growth of children with SCD and the age at which they attained peak height velocity. PROCEDURE: A retrospective chart review was performed recording weight, height, and body mass index (BMI) measurements of 36 patients with SCD who received LTE every 3-5 weeks for an average duration of 5 years. The z-scores for weight, height, and BMI of these patients were compared with that of patients with SCD from the Cooperative Study of Sickle Cell Disease (CSSCD) and a sub-set of 64 controls matched for age, sex, and initial growth parameter z-scores at the start of LTE. RESULTS: The z-scores for all parameters improved significantly for our patients on LTE compared to match controls from CSSCD and the entire pediatric CSSCD cohort (P-value: <0.01). Peak height velocity was achieved 2 months earlier for females (P-value: 0.94) and 11 months earlier for males (P-value: 0.02), who started LTE before 14 years of age, compared to matched CSSCD controls. The study subjects who had not been on regular simple transfusions prior to starting LTE had a mean serum ferritin of 681 ng/ml after LTE for an average duration of 63 months. CONCLUSION: LTE improves the growth of children with SCD without the risk of iron overload. PMID- 25111890 TI - Replica exchange Monte Carlo simulation of human serum albumin-catechin complexes. AB - Replica exchange Monte Carlo simulation equipped with an orientation-enhanced hydrophobic interaction was utilized to study the impacts of molar ratio and ionic strength on the complex formation of human serum albumin (HSA) and catechin. Only a small amount of catechins was found to act as bridges in the formation of HSA-catechin complexes. Selective binding behavior was observed at low catechin to HSA molar ratio (R). Increase of catechin amount can suppress HSA self-aggregation and diminish the selectivity of protein binding sites. Strong saturation binding with short-range interactions was found to level off at around 4.6 catechins per HSA on average, while this number slowly increased with R when long-range interactions were taken into account. Meanwhile, among the three rings of catechin, the 3,4-dihydroxyphenyl (B-ring) shows the strongest preference to bind HSA. Neither the aggregation nor the binding sites of the HSA-catechin complex was sensitive to ionic strength, suggesting that the electrostatic interaction is not a dominant force in such complexes. These results provide a further molecular level understanding of protein-polyphenol binding, and the strategy employed in this work shows a way to bridge phase behaviors at macroscale and the distribution of binding sites at residue level. PMID- 25111887 TI - Glycyrrhizin protects brain against ischemia-reperfusion injury in mice through HMGB1-TLR4-IL-17A signaling pathway. AB - High mobility group box 1 (HMGB1)-Toll-like receptor 4 (TLR4) signaling has been recently found to induce interleukin (IL)-17A secretion in drug-induced hepatitis and myocardial I/R injury. The purpose of this study is to evaluate whether HMGB1 TLR4 signaling could induce IL-17A secretion and lead to brain I/R injury. We also sought to investigate whether glycyrrhizin elucidated its neuroprotective effects through HMGB1-TLR4-IL-17A signaling pathway. Various biochemical estimations, neurological status, and assessment of cerebral infarct size were carried out 72h after middle cerebral artery occlusion (MCAO) stroke. Apoptotic cells were assessed using a terminal deoxynucleotidyl transferase, dUTP nick and labeling (TUNEL) kit. The expression of HMGB1, IL-17A, bcl-2, bax and cleaved caspase-3, were determined by Western blot assay. In the present study we found that glycyrrhizin significantly decreased HMGB1 protein expression. Glycyrrhizin markedly reduced whereas recombinant HMGB1 (rHMGB1) increased IL-17A expression. HMGB1 induced increase of IL-17A was significantly diminished in TLR4-mutant C3H/HeJ mice. Brain injury and neurological deficits were largely abrogated by glycyrrhizin or IL-17A knockout. In contrast, rHMGB1 or recombinant mouse IL-17A markedly increased I/R injury. However, rHMGB1 had no effects on infarct size and neurological deficits in Il17a(-/-) mice following brain I/R injury. In addition, IL-17A knockout mice significantly increased bcl-2 protein expression and had fewer apoptotic cells, whereas recombinant IL-17A-treated mice significantly increased bax and cleaved caspase-3 protein expression and had more apoptotic cells. Together these results indicate that glycyrrhizin has neuroprotective efficacy in the postischemic brain through HMGB1-TLR4-IL-17A signaling pathway. PMID- 25111891 TI - Poor outcome and death among youth, young adults, and midlife adults with eating disorders: an investigation of risk factors by age at assessment. AB - OBJECTIVE: Eating disorders (EDs) present across a broad age range, yet little is known about the characteristics and outcome of midlife patients compared to younger patients. Among patients seeking ED treatment who were stratified by age at initial assessment (IA), this study aimed to (1) discern sociodemographic and clinical differences, (2) determine outcome rates, and (3) identify predictors of poor outcome including death. METHOD: Participants [219 females (12 years or older, 94.1% Caucasian) who completed outcome assessment and 31 known decedents] were stratified by age at IA (<18 as youth, 18-39 as young adult, and >=40 years as midlife adult). Analyses of variance and chi-square tests identified group differences; ordered logistic regression with stepwise selection identified factors predicting outcome. RESULTS: Midlife adults were more significantly compromised at follow-up compared to youths and young adults, including psychological and physical quality of life, ineffectiveness, interpersonal concerns, and general psychological maladjustment. Midlife adults had the highest rates of poor outcome or death; good outcome was achieved by only 5.9% of midlife adult compared to 14.0% of young adult and 27.5% of youth patients. Older age at IA, alcohol and/or drug misuse, endocrine concerns, and absence of family ED history predicted poor outcome or death. DISCUSSION: Midlife adults seeking ED treatment have more complex medical and psychological concerns and poorer outcomes than youths and young adults; further exploration is needed to improve treatment outcome. Specialized treatment focusing on quality of life, comorbid medical concerns, interpersonal connection, and emotion regulation is encouraged. PMID- 25111892 TI - Designed synthesis of a highly conjugated hexaethynylbenzene-based host for supramolecular architectures. AB - The construction of efficient synthetic functional receptors with tunable cavities, and the self-organization of guest molecules within these cavities through noncovalent interactions can be challenging. Here we have prepared a double-cavity molecular cup based on hexaethynylbenzene that possesses a highly pi-conjugated interior for the binding of electron-rich guests. X-ray crystallography, NMR spectroscopy, UV/Vis spectroscopy, fluorescent spectroscopy, cyclic voltammetry, and SEM were used to investigate the structures and the binding behaviors. The results indicated that the binding of a guest in one cavity would affect the binding of the same or another guest in the other cavity. The effect of electron transfer in this system suggests ample opportunities for tuning the optical and electronic properties of the molecular cup and the encapsulated guest. The encapsulation of different guests would also lead to different aggregate nanostructures, which is a new way to tune their supramolecular architectures. PMID- 25111893 TI - Introducing diagnosis-related groups: is the information system ready? AB - Diagnosis-related group (DRG) system is a classification system widely used in health managements, the foundation of which lies in the medical information system. A large effort had been made to improve the quality of discharge data before the introduction of DRGs in Beijing. We extract discharge data from 108 local hospitals spanning 4 years before and after standardization to evaluate the impact of standardization on DRG grouping performance. The data was grouped on an annual basis in accordance with Beijing's local DRG system. Proportion of ungrouped data, coefficient of variation (CV) and reduction in variance (RIV) were used to measure the performance of the DRG system. Both the descriptive and regression analysis indicate a significant reduction in terms of ungrouped data and CV for expenditure, increase of RIV for expenditure and length of stay. However, when there was no intervention, that is, between 2005 and 2006 and between 2008 and 2009, changes in these indicators were all insignificant. Therefore, the standardization of discharge data did improve data quality and consequently enhanced the performance of DRGs. Developing countries with a relatively weak information infrastructure should strengthen their medical information system before the introduction of the DRG system. PMID- 25111894 TI - Erythematous-to-brownish plaques on the upper back: a quiz. Phenytoin-induced T cell predominant pseudolymphoma ("pseudomycosis fungoides") with T-cell clonality. PMID- 25111896 TI - Cell death induced by 2-phenylethynesulfonamide uncovers a pro-survival function of BAX. AB - PES (2-phenylethynesulfonamide) was initially identified as an inhibitor of p53 translocation to mitochondria and named Pifithrin-u. Further studies showed that PES selectively killed tumour cells and was thus a promising anticancer agent. PES-induced cell death was characterised by a non-apoptotic, autophagosome-rich phenotype. We observed this phenotype via electron microscopy in wild type (wt) and double Bax-/- Bak-/- (DKO) mouse embryonic fibroblasts (MEFs) treated with PES. We excluded the involvement of effector caspases, BAX and BAK, in causing PES-triggered cell death. Therefore, apoptosis was ruled out as the lethal mode of action of PES. Surprisingly, MEFs containing BAX were significantly protected from PES treatments. BAX overexpression in Bax-/- MEFs confirmed this pro survival effect. Moreover, this protective effect required the ability of BAX to localise to mitochondrial membranes. Conversely, mitochondrial fusion induced by treatment with Mdivi-1 conferred increased resistance to MEFs subjected to PES treatment. The involvement of BAX in the regulation of mitochondrial dynamics has been reported. We propose the promotion of mitochondrial fusion by BAX to be the pro-survival function attributed to BAX. PMID- 25111895 TI - The use of valproic acid and multiple sclerosis. AB - BACKGROUND: Animal studies have suggested that drugs inhibiting the enzyme histone deacetylase might have a beneficial effect on multiple sclerosis (MS). Valproic acid (VPA), an anti-epileptic drug, is the only widely used human drug with a histone deacetylase inhibitory effect. OBJECTIVE: The objective of this paper is to examine if VPA use is associated with a reduced risk of MS. METHODS: We conducted a propensity score-matched cohort study in the period 1997-2011 linking nationwide register data on filled VPA prescriptions, MS cases, and several covariates. The VPA users were matched on propensity scores in a 1:4 ratio with non-users of VPA. Incidence rates of MS were compared among VPA users and non-users of VPA using Cox regression to estimate hazard ratios (HRs). RESULTS: Among 16 028 ever-users of VPA and 54 172 non-users, 18 and 26 cases of MS were identified, respectively. Neither current VPA users nor recent users of VPA, who had ceased VPA treatment within the last year, were at a reduced risk of MS compared with non-users of VPA (HR = 1.30 (95% confidence interval, 0.44 3.80), n = 4, and HR = 1.22 (0.28-5.32), n = 2, respectively). Similarly, in an intention-to-treat analysis, ever-users of VPA were not at reduced risk of MS (HR = 2.41 (1.32-4.43), n = 18). CONCLUSION: In the first human study addressing a possible beneficial effect of VPA use on the risk of MS, we found no support for a protective effect. However, given the wide confidence intervals, only large effects can be ruled out with sufficient certainty. PMID- 25111897 TI - HDAC6 sustains growth stimulation by prolonging the activation of EGF receptor through the inhibition of rabaptin-5-mediated early endosome fusion in gastric cancer. AB - The aberrant regulation of histone deacetylase 6 (HDAC6) contributes to malignant progression in various types of cancer, but the mechanism underlying gastric carcinogenesis remains unknown. Aberrant HDAC6 overexpression was observed in a subset of human gastric cancer cells. HDAC6 knockdown caused the significant inhibition of gastric cancer cell growth without affecting the transition of cell cycles or the processing of cell death. We demonstrate that an increase in epidermal growth factor receptor (EGFR) signaling through decreased EGFR degradation was mediated by HDAC6 in gastric carcinogenesis. These results establish a molecular mechanism responsible for oncogenic HDAC6, explaining how EGFR signaling induced by the growth factor is sustained during the malignant progression of gastric cancer. PMID- 25111898 TI - Gain-of-function of mutant p53: mutant p53 enhances cancer progression by inhibiting KLF17 expression in invasive breast carcinoma cells. AB - Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis and epithelial-mesenchymal-transition (EMT). However, its expression is downregulated in metastatic breast cancer that contains p53 mutations. Here, we show that mutant-p53 plays a key role to suppress KLF17 and thereby enhances cancer progression, which defines novel gain-of-function (GOF) of mutant-p53. Mutant-p53 interacts with KLF17 and antagonizes KLF17 mediated EMT genes transcription. Depletion of KLF17 promotes cell viability, decreases apoptosis and induces drug resistance in metastatic breast cancer cells. KLF17 suppresses cell migration and invasion by decreasing CD44, PAI-1 and Cyclin-D1 expressions. Taken together, our results show that KLF17 is important for the suppression of metastasis and could be a potential therapeutic target during chemotherapy. PMID- 25111900 TI - Streaming potential near a rotating porous disk. AB - Theory and experimental results for the streaming potential measured in the vicinity of a rotating porous disk-shaped sample are described. Rotation of the sample on its axis draws liquid into its face and casts it from the periphery. Advection within the sample engenders streaming current and streaming potential that are proportional to the zeta potential and the disk's major dimensions. When Darcy's law applies, the streaming potential is proportional to the square of the rotation at low rate but becomes invariant with rotation at high rate. The streaming potential is invariant with the sample's permeability at low rate and is proportional to the inverse square of the permeability at high rate. These predictions were tested by determining the zeta potential and permeability of the loop side of Velcro, a sample otherwise difficult to characterize; reasonable values of -56 mV for zeta and 8.7 * 10(-9) m(2) for the permeability were obtained. This approach offers the ability to determine both the zeta potential and the permeability of materials having open structures. Compressing them into a porous plug is unnecessary. As part of the development of the theory, a convenient formula for a flow-weighted volume-averaged space-charge density of the porous medium, -epsilonzeta/k, was obtained, where epsilon is the permittivity, zeta is the zeta potential, and k is the Darcy permeability. The formula is correct when Smoluchowski's equation and Darcy's law are both valid. PMID- 25111901 TI - Pulsed transfer etching of PS-PDMS block copolymers self-assembled in 193 nm lithography stacks. AB - This work presents the graphoepitaxy of high-chi block copolymers (BCP) in standard industry-like lithography stacks and their transfer into the silicon substrate The process includes conventional 193 nm photolithography, directed self-assembly of polystyrene-block-polydimethylsiloxane (PS-b-PDMS) and pulsed plasma etching to transfer the obtained features into the substrate. PS-b-PDMS has a high Flory-Huggins interaction parameter (high-chi) and is capable of achieving sub-10 nm feature sizes. The photolithography stack is fabricated on 300 mm diameter silicon wafers and is composed of three layers: spin-on-carbon (SoC), silicon-containing anti-reflective coating (SiARC) and 193 nm photolithography resist. Sixty-nanometer-deep trenches are first patterned by plasma etching in the SiARC/SoC stack using the resist mask. The PS-b-PDMS is then spread on the substrate surface. Directed self-assembly (DSA) of the BCP is induced by a solvent vapor annealing process and PDMS cylinders parallel to the substrate surface are obtained. The surface chemistry based on SoC permits an efficient etching process into the underlying silicon substrate. The etching process is performed under dedicated pulsed plasma etching conditions. Fifteen nanometer half-pitch dense line/space features are obtained with a height up to 90 nm. PMID- 25111902 TI - Spectral entropy, ecological resilience, and adaptive capacity for understanding, evaluating, and managing ecosystem stability and change. PMID- 25111903 TI - Synthesis of polymeric phosphonates for selective delivery of radionuclides to osteosarcoma. AB - Discussed in detail is the synthesis and primary structure characterization of two polymers aimed at advancing the treatment of pediatric osteosarcoma. These polymers are designed to systemically deliver radiometals specifically to osteosarcomas using the passive targeting mechanism of enhanced permeability and retention (the EPR effect). The approach begins with the synthesis of a polymer capable of binding radiometals, for which prior data show improved site-specific targeting of solid tumors. Building on this success, a second polymer has been designed for improving the efficacy of currently available radionuclide therapies by incorporating the FDA-approved small-molecule ligand Quadramet directly onto the polymer structure. Time-activity curves of the phosphonate-functionalized polymers show rapid clearance from the central compartment and nontargeted organs, with up to 65% of injected activity being excreted within 3 hours. Both polymer ligands demonstrate good osteosarcoma targeting capability with little to no uptake in organs associated with the dose-limiting bone marrow. Additionally, biodistribution studies in nonosseous tumor models demonstrate the tumor targeting mechanism of the polymer ligands, which appears to be influenced by the high affinity of the phosphonate functionality for the positively charged hydroxyapatite mineral found in bone tumors. PMID- 25111904 TI - Preparation and electric property of polysilsesquioxane thin films incorporating carbazole groups. AB - New silsesquioxane incorporating a carbazole groups (PCTSQ) has been synthesized by a click thiol-ene reaction and a subsequent sol-gel reaction. To evaluate the electric property of this hybrid, diode devices have been fabricated by using PCTSQ thin film by spin-coating onto n-type ZnO film prepared by the electrodeposition method. The thin film hybrid devices showed good electric characteristics and high rectification ratio, as well as worked as a rectifier. PMID- 25111905 TI - Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-alpha administered to the buccal mucosa. AB - Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection(r)). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses. PMID- 25111899 TI - A new model army: Emerging fish models to study the genomics of vertebrate Evo Devo. AB - Many fields of biology--including vertebrate Evo-Devo research--are facing an explosion of genomic and transcriptomic sequence information and a multitude of fish species are now swimming in this "genomic tsunami." Here, we first give an overview of recent developments in sequencing fish genomes and transcriptomes that identify properties of fish genomes requiring particular attention and propose strategies to overcome common challenges in fish genomics. We suggest that the generation of chromosome-level genome assemblies--for which we introduce the term "chromonome"--should be a key component of genomic investigations in fish because they enable large-scale conserved synteny analyses that inform orthology detection, a process critical for connectivity of genomes. Orthology calls in vertebrates, especially in teleost fish, are complicated by divergent evolution of gene repertoires and functions following two rounds of genome duplication in the ancestor of vertebrates and a third round at the base of teleost fish. Second, using examples of spotted gar, basal teleosts, zebrafish related cyprinids, cavefish, livebearers, icefish, and lobefin fish, we illustrate how next generation sequencing technologies liberate emerging fish systems from genomic ignorance and transform them into a new model army to answer longstanding questions on the genomic and developmental basis of their biodiversity. Finally, we discuss recent progress in the genetic toolbox for the major fish models for functional analysis, zebrafish, and medaka, that can be transferred to many other fish species to study in vivo the functional effect of evolutionary genomic change as Evo-Devo research enters the postgenomic era. PMID- 25111906 TI - Ellagitannins as synergists of ACV on the replication of ACV-resistant strains of HSV 1 and 2. AB - The plant-derived polyphenolic compounds castalagin, vescalagin and grandinin (C glucosidic ellagitannins containing nonahydroxyterphenoyl) manifested a strong inhibitory effect on the replication of acyclovir-resistant strains of herpes simplex viruses (HSV) type 1 and 2 in MDBK cells in focus forming units (i.e., microscopically registered microplaques) reduction assay and in two variants of cytopathic effect inhibition test. The effect on the acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) strain was markedly higher compared to that on the ACV-resistant herpes simplex virus type 2 (HSV-2). The three compounds showed comparable levels of antiviral activity against ACV-resistant HSV strains, in contrast with previous results where castalagin exerted the highest degree of activity against wild type HSV strains (Vilhelmova et al., 2011). Combinations of ellagitannins and ACV were tested on the ACV-resistant strains of both HSV-1 and 2 and produced synergistic effects that were revealed by applying the three dimensional approach of Prichard and Shipman (1990). The ellagitannin(s)-ACV combination applied against ACV-resistant HSV-1 produced a much stronger synergistic effect compared to the effect observed against ACV-resistant HSV-2. The study of the effects of the combination ellagitannin(s)-ACF on intact cell monolayers did not show any toxicity resulting from interaction between the two substances. Altogether, the results obtained in this study demonstrate the highly promising potential of these plant polyphenols as antiherpetic agents. PMID- 25111908 TI - Highly efficient hybrid solar cells with tunable dipole at the donor-acceptor interface. AB - Effects of molecular dipole at the conjugated polymer-nanocrystal interface on the energy level alignment, the exciton dissociation process, and consequently the photovoltaic performance of poly[2,6-(4,4-bis-(2-ethylhexyl)-4H cyclopenta[2,1-b;3,4-b']-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT):CdSe quantum dot bulk heterojunction hybrid solar cells are systemically studied. Power conversion efficiency up to 4.0% is achieved when 4 fluorobenzenethiol is used for ligand exchange. PMID- 25111907 TI - Improving rheology and enzymatic hydrolysis of high-solid corncob slurries by adding lignosulfonate and long-chain fatty alcohols. AB - The effects of lignosulfonate (SXSL) and long-chain fatty alcohols (LFAs) on the rheology and enzymatic hydrolysis of high-solid corncob slurries were investigated. The application of 2.5% (w/w) SXSL increased the substrate enzymatic digestibility (SED) of high-solid corncob slurries at 72 h from 31.7 to 54.0%, but meanwhile it increased the slurry's yield stress and complex viscosity to make the slurry difficult to stir and pump. The smallest molecular weight (MW) SXSL fraction had the strongest enhancement on SED. The SXSL fraction with large MW had a negative effect on rheology. n-Octanol (C8) and n-decanol (C10) improved the rheological properties of high-solid slurry and are strong enough to counteract the negative effect of SXSL. Furthermore, C8 and C10 clearly enhanced the enzymatic hydrolysis of high-solid corncob slurries with and without SXSL. A mechanism was proposed to explain the observed negative effect of SXSL and the positive effect of LFAs on the rheological properties. PMID- 25111909 TI - Stable single-molecule lines of terrylene in polycrystalline para-dichlorobenzene at 1.5 K. AB - The spectroscopic properties of single terrylene (Tr) molecules are studied in a polycrystalline matrix of para-dichlorobenzene (p-DCB) at 1.5 K. Samples grown in a glass capillary show a very strong site at 597 nm, which is redshifted by more than 700 cm(-1) from the observed transition energy for Tr in p-DCB prepared as a film on a coverslip (572 nm). Each of these two sites is characterized by measuring their single-molecule spectroscopic parameters at 1.5 K. Lifetime limited linewidths of 45+/-5 MHz are found for both sites. Fluorescence detection rates reach 8*10(4) count s(-1) at saturation. The spectral trails of the majority of single molecules show no spectral jumps, indicating an absence of interacting two-level systems; however, the small distribution of linewidths may indicate weak interactions with low-frequency modes. Frequency jumps are observed for 10 % of the molecules. The complete emission spectra from two different single molecules at the center of each of the two sites is presented. Debye Waller factors of alphaDW=0.33+/-0.05 for the normal site (572 nm) and alphaDW=0.30+/-0.05 for the red site (597 nm) are reported. This new host-guest system provides a quick and easy way to obtain lifetime-limited single-molecule lines. PMID- 25111910 TI - Fragmentation of urinary calculi in vitro by burst wave lithotripsy. AB - PURPOSE: We developed a new method of lithotripsy that uses short, broadly focused bursts of ultrasound rather than shock waves to fragment stones. We investigated the characteristics of stone comminution by burst wave lithotripsy in vitro. MATERIALS AND METHODS: Artificial and natural stones (mean +/- SD size 8.2 +/- 3.0 mm, range 5 to 15) were treated with ultrasound bursts using a focused transducer in a water bath. Stones were exposed to bursts with focal pressure amplitude of 6.5 MPa or less at a 200 Hz burst repetition rate until completely fragmented. Ultrasound frequencies of 170, 285 and 800 kHz were applied using 3 transducers, respectively. Time to fragmentation for each stone type was recorded and fragment size distribution was measured by sieving. RESULTS: Stones exposed to ultrasound bursts were fragmented at focal pressure amplitudes of 2.8 MPa or greater at 170 kHz. Fractures appeared along the stone surface, resulting in fragments that separated at the surface nearest to the transducer until the stone was disintegrated. All natural and artificial stones were fragmented at the highest focal pressure of 6.5 MPa with a mean treatment duration of 36 seconds for uric acid stones to 14.7 minutes for cystine stones. At a frequency of 170 kHz the largest artificial stone fragments were less than 4 mm. Exposure at 285 and 800 kHz produced only fragments less than 2 mm and less than 1 mm, respectively. CONCLUSIONS: Stone comminution with burst wave lithotripsy is feasible as a potential noninvasive treatment method for nephrolithiasis. Adjusting the fundamental ultrasound frequency allows for stone fragment size to be controlled. PMID- 25111912 TI - Early discontinuation of antibiotic prophylaxis in patients with persistent primary vesicoureteral reflux initially detected during infancy: outcome analysis and risk factors for febrile urinary tract infection. AB - PURPOSE: We retrospectively assessed the incidence of and risk factors for febrile urinary tract infection in children during active surveillance after early discontinuation of antibiotic prophylaxis. MATERIALS AND METHODS: We retrospectively evaluated 9 females and 61 uncircumcised males diagnosed with primary vesicoureteral reflux before age 1 year who had persistent reflux on followup voiding cystourethrogram and were subsequently followed under active surveillance without continuous antibiotic prophylaxis. Patients with secondary vesicoureteral reflux or associated urological abnormality were excluded. Clinical outcomes, including incidence of febrile urinary tract infection and new scar formation, were evaluated. Risk factors for febrile urinary tract infection were also analyzed. RESULTS: Mean age at stopping continuous antibiotic prophylaxis was 21 months, and mean followup was 61 months. During active surveillance 21 patients had febrile urinary tract infection, and the 5-year infection-free rate under active surveillance was 67.5%. One or 2 foci of minimal new scarring developed in 4 of 16 patients who underwent followup dimercapto succinic acid scan after febrile urinary tract infection. On multivariate analysis dilated vesicoureteral reflux on followup voiding cystourethrogram was the only significant risk factor for febrile urinary tract infection. CONCLUSIONS: This study revealed that about two-thirds of patients with persistent vesicoureteral reflux were free of febrile urinary tract infection during 5 years of active surveillance. Those with dilated vesicoureteral reflux on followup voiding cystourethrogram are at significantly greater risk for febrile urinary tract infection. Accordingly active surveillance, especially in patients with nondilated vesicoureteral reflux on followup voiding cystourethrogram, seems to be a safe option even in children who have not yet been toilet trained. PMID- 25111911 TI - Fluoroquinolone resistance in the rectal carriage of men in an active surveillance cohort: longitudinal analysis. AB - PURPOSE: Rectal swabs can identify men with fluoroquinolone resistant bacteria and decrease the infection rate after transrectal ultrasound guided prostate biopsy by targeted antimicrobial prophylaxis. We evaluated the rate of fluoroquinolone resistance in an active surveillance cohort with attention to factors associated with resistance and changes in resistance with time. MATERIALS AND METHODS: We evaluated 416 men with prostate cancer on active surveillance who underwent rectal swabs to assess the rate of fluoroquinolone resistance compared to that in men undergoing diagnostic transrectal ultrasound guided prostate biopsy. The chi-square test and Student t-test were used to compare categorical and continuous variables, respectively. Poisson regression analysis was used for multivariate analysis. RESULTS: On the initial swab fluoroquinolone resistance was found in 95 of 416 men (22.8%) on active surveillance compared to 54 of 221 (24.4%) in the diagnostic biopsy cohort (p = 0.675). Diabetes was found in 4.0% of the fluoroquinolone sensitive group vs 14.7% of the resistant group (p <0.001). Biopsy history was not associated with resistance. Of those with a resistant first swab 62.9% had a resistant second swab and 88.9% of those with 2 resistant swabs showed resistance on the third swab. Of men with a sensitive first swab 10.6% showed resistance on the second swab and 10.6% of those with 2 sensitive swabs had resistant third swabs. CONCLUSIONS: One of 4 men who present for surveillance and diagnostic transrectal ultrasound guided prostate biopsy have rectal flora resistant to fluoroquinolone. Resistance is significantly associated with diabetes but the number of prior biopsies is not. Men with fluoroquinolone resistant flora tend to remain resistant with time. PMID- 25111913 TI - Histological analysis of the kidney tumor-parenchyma interface. AB - PURPOSE: During enucleative partial nephrectomy excision is performed adjacent to the tumor edge. To better determine the oncologic propriety of enucleative partial nephrectomy we histologically examined the tumor-parenchyma interface. MATERIALS AND METHODS: Archived hematoxylin and eosin stained slides of 124 nephrectomy specimens were rereviewed. We evaluated representative sections of tumor abutting the renal parenchyma and overlying pseudocapsule/perirenal fat were selected at 4 mm(2) sectors apportioned 1, 2, 3 and 4 mm, respectively, from the tumor edge. RESULTS: Median tumor size was 3.5 cm. Of the tumors 111 were malignant (90%) and 119 (96%) had a pseudocapsule with a median thickness of 0.6 mm. Of malignant and benign tumors 82% and 31%, respectively, had an intrarenal pseudocapsule (p < 0.001). Pseudocapsule invasion was noted in 45% of cancers and 15% of benign tumors (p < 0.04). Of pT1a cancers 36% showed intrarenal pseudocapsule invasion. No patient had positive surgical margins. Intrarenal pseudocapsule invasion correlated with clear cell renal cell carcinoma histology but not with cancer size, grade, necrosis or margin width. Inflammation, nephrosclerosis, glomerulosclerosis and arteriosclerosis decreased with increasing distance from the tumor edge. At 1 mm changes were moderate to severe in 38%, 32%, 20% and 17% of tumors while at 5 mm changes were mild in 2.5%, 0.8%, 0.8% and 4%, respectively (p <0.001). Mean arteriolar diameter decreased with tumor proximity (p < 0.0001). CONCLUSIONS: Most renal cancers have an intrarenal pseudocapsule. Partial nephrectomy excision adjacent to the tumor edge appears to be histologically safe. Because 18% of cancers lacked a discernible intrarenal pseudocapsule and 25% of pT1a cancers showed intrarenal pseudocapsule invasion, extreme care is needed to avoid positive margins during enucleative partial nephrectomy. PMID- 25111914 TI - Endometriosis, endocervicosis and mullerianosis of the bladder. PMID- 25111915 TI - Data requirements for electronic surveillance of healthcare-associated infections. AB - Electronic surveillance for healthcare-associated infections (HAIs) is increasingly widespread. This is driven by multiple factors: a greater burden on hospitals to provide surveillance data to state and national agencies, financial pressures to be more efficient with HAI surveillance, the desire for more objective comparisons between healthcare facilities, and the increasing amount of patient data available electronically. Optimal implementation of electronic surveillance requires that specific information be available to the surveillance systems. This white paper reviews different approaches to electronic surveillance, discusses the specific data elements required for performing surveillance, and considers important issues of data validation. PMID- 25111917 TI - Antimicrobial stewardship strategies: preauthorization or postprescription audit and feedback? PMID- 25111916 TI - Comparison of prior authorization and prospective audit with feedback for antimicrobial stewardship. AB - OBJECTIVE: Although prior authorization and prospective audit with feedback are both effective antimicrobial stewardship program (ASP) strategies, the relative impact of these approaches remains unclear. We compared these core ASP strategies at an academic medical center. DESIGN: Quasi-experimental study. METHODS: We compared antimicrobial use during the 24 months before and after implementation of an ASP strategy change. The ASP used prior authorization alone during the preintervention period, June 2007 through May 2009. In June 2009, many antimicrobials were unrestricted and prospective audit was implemented for cefepime, piperacillin/tazobactam, and vancomycin, marking the start of the postintervention period, July 2009 through June 2011. All adult inpatients who received more than or equal to 1 dose of an antimicrobial were included. The primary end point was antimicrobial consumption in days of therapy per 1,000 patient-days (DOT/1,000-PD). Secondary end points included length of stay (LOS). RESULTS: In total, 55,336 patients were included (29,660 preintervention and 25,676 postintervention). During the preintervention period, both total systemic antimicrobial use (-9.75 DOT/1,000-PD per month) and broad-spectrum anti-gram negative antimicrobial use (-4.00 DOT/1,000-PD) declined. After the introduction of prospective audit with feedback, however, both total antimicrobial use (+9.65 DOT/1,000-PD per month; P < .001) and broad-spectrum anti-gram-negative antimicrobial use (+4.80 DOT/1,000-PD per month; P < .001) increased significantly. Use of cefepime and piperacillin/tazobactam both significantly increased after the intervention (P = .03). Hospital LOS and LOS after first antimicrobial dose also significantly increased after the intervention (P = .016 and .004, respectively). CONCLUSIONS: Significant increases in antimicrobial consumption and LOS were observed after the change in ASP strategy. PMID- 25111918 TI - Development of an antibiotic spectrum score based on veterans affairs culture and susceptibility data for the purpose of measuring antibiotic de-escalation: a modified Delphi approach. AB - OBJECTIVE: Development of a numerical score to measure the microbial spectrum of antibiotic regimens (spectrum score) and method to identify antibiotic de escalation events based on application of the score. DESIGN: Web-based modified Delphi method. PARTICIPANTS: Physician and pharmacist antimicrobial stewards practicing in the United States recruited through infectious diseases-focused listservs. METHODS: Three Delphi rounds investigated: organisms and antibiotics to include in the spectrum score, operationalization of rules for the score, and de-escalation measurement. A 4-point ordinal scale was used to score antibiotic susceptibility for organism-antibiotic domain pairs. Antibiotic regimen scores, which represented combined activity of antibiotics in a regimen across all organism domains, were used to compare antibiotic spectrum administered early (day 2) and later (day 4) in therapy. Changes in spectrum score were calculated and compared with Delphi participants' judgments on de-escalation with 20 antibiotic regimen vignettes and with non-Delphi steward judgments on de escalation of 300 pneumonia regimen vignettes. Method sensitivity and specificity to predict expert de-escalation status were calculated. RESULTS: Twenty-four participants completed all Delphi rounds. Expert support for concepts utilized in metric development was identified. For vignettes presented in the Delphi, the sign of change in score correctly classified de-escalation in all vignettes except those involving substitution of oral antibiotics. The sensitivity and specificity of the method to identify de-escalation events as judged by non Delphi stewards were 86.3% and 96.0%, respectively. CONCLUSIONS: Identification of de-escalation events based on an algorithm that measures microbial spectrum of antibiotic regimens generally agreed with steward judgments of de-escalation status. PMID- 25111919 TI - Multisite exploration of clinical decision making for antibiotic use by emergency medicine providers using quantitative and qualitative methods. AB - OBJECTIVES: To explore current practices and decision making regarding antimicrobial prescribing among emergency department (ED) clinical providers. METHODS: We conducted a survey of ED providers recruited from 8 sites in 3 cities. Using purposeful sampling, we then recruited 21 providers for in-depth interviews. Additionally, we observed 10 patient-provider interactions at one of the ED sites. SAS 9.3 was used for descriptive and predictive statistics. Interviews were audio recorded, transcribed, and analyzed using a thematic, constructivist approach with consensus coding using NVivo 10.0. Field and interview notes collected during the observational study were aligned with themes identified through individual interviews. RESULTS: Of 150 survey respondents, 76% agreed or strongly agreed that antibiotics are overused in the ED, while half believed they personally did not overprescribe. Eighty-nine percent used a smartphone or tablet in the ED for antibiotic prescribing decisions. Several significant differences were found between attending and resident physicians. Interview analysis identified 42 codes aggregated into the following themes: (1) resource and environmental factors that affect care; (2) access to and quality of care received outside of the ED consult; (3) patient-provider relationships; (4) clinical inertia; and (5) local knowledge generation. The observational study revealed limited patient understanding of antibiotic use. Providers relied heavily upon diagnostics and provided limited education to patients. Most patients denied a priori expectations of being prescribed antibiotics. CONCLUSIONS: Patient, provider, and healthcare system factors should be considered when designing interventions to improve antimicrobial stewardship in the ED setting. PMID- 25111920 TI - Infection prevention practices in neonatal intensive care units reporting to the national healthcare safety network. AB - BACKGROUND: Patients in the neonatal intensive care unit (NICU) are at high risk for healthcare-associated infections. Variability in reported infection rates among NICUs exists, possibly related to differences in prevention strategies. A better understanding of current prevention practices may help identify prevention gaps and areas for further research. METHODS: We surveyed infection control staff in NICUs reporting to the National Healthcare Safety Network (NHSN) to assess strategies used to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission and central line-associated bloodstream infections in NICUs. RESULTS: Staff from 162 of 342 NICUs responded (response rate, 47.3%). Most (92.3%) NICUs use central line insertion and maintenance bundles, but maintenance practices varied, including agents used for antisepsis and frequency of dressing changes. Forty-two percent reported routine screening for MRSA colonization upon admission for all patients. Chlorhexidine gluconate (CHG) use for central line care for at least 1 indication (central line insertion, dressing changes, or port/cap antisepsis) was reported in 82 NICUs (51.3%). Among sixty-five NICUs responding to questions on CHG use restrictions, 46.2% reported no restrictions. CONCLUSIONS: Our survey illustrated heterogeneity of CLABSI and MRSA prevention practices and underscores the need for further research to define optimal strategies and evidence-based prevention recommendations for neonates. PMID- 25111921 TI - The association of state legal mandates for data submission of central line associated bloodstream infections in neonatal intensive care units with process and outcome measures. AB - OBJECTIVE: To determine the association between state legal mandates for data submission of central line-associated bloodstream infections (CLABSIs) in neonatal intensive care units (NICUs) with process and outcome measures. DESIGN: Cross-sectional study. PARTICIPANTS: National sample of level II/III and III NICUs participating in National Healthcare Safety Network (NHSN) surveillance. METHODS: State mandates for data submission of CLABSIs in NICUs in place by 2011 were compiled and verified with state healthcare-associated infection coordinators. A web-based survey of infection control departments in October 2011 assessed CLABSI prevention practices, ie, compliance with checklist/bundle components (process measures) in ICUs including NICUs. Corresponding 2011 NHSN NICU CLABSI rates (outcome measures) were used to calculate standardized infection ratios (SIRs). Association between mandates and process and outcome measures was assessed by multivariable logistic regression. RESULTS: Among 190 study NICUs, 107 (56.3%) were located in states with mandates, with mandates in place >3 years in 52 (49%). More NICUs in states with mandates reported >=95% compliance to at least 1 CLABSI prevention practice (52.3%-66.4%) than NICUs in states without mandates (28.9%-48.2%). Mandates were predictors of >=95% compliance with all practices (odds ratio, 2.8; 95% confidence interval, 1.4 6.1). NICUs in states with mandates reported lower mean CLABSI rates in the <=750 g birth weight group (2.4 vs 5.7 CLABSIs/1,000 central line-days) but not in others. Mandates were not associated with SIR <1. CONCLUSIONS: State mandates for NICU CLABSI data submission were significantly associated with >=95% compliance with CLABSI prevention practices, which declined with the duration of mandate but not with lower CLABSI rates. PMID- 25111922 TI - The effect of multiple concurrent central venous catheters on central line associated bloodstream infections. AB - OBJECTIVE: The current central line-associated bloodstream infection (CLABSI) surveillance rate calculation does not account for multiple concurrent central venous catheters (CVCs). The presence of multiple CVCs creates more points of entry into the bloodstream, potentially increasing CLABSI risk. Multiple CVCs may be used in sicker patients, making it difficult to separate the relative contributions of multiple CVCs and comorbidities to CLABSI risk. We explored the relative impact of multiple CVCs, patient comorbidities, and disease severity on the risk of CLABSI. DESIGN: Case-control study. SETTING: A total of 197 case patients and 201 control subjects with a CVC inserted during hospitalization at a tertiary care academic medical center from January 1, 2008, to December 31, 2010. METHODS: Multiple CVCs was the exposure of interest; the primary outcome was CLABSI. Multivariable logistic regression was conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) describing the association between CLABSI and multiple CVCs with and without controlling for Acute Physiology and Chronic Health Evaluation (APACHE) II and Charlson comorbidity index (CCI) scores as measures of disease severity and patient comorbidities, respectively. RESULTS: Patients with multiple CVCs (n = 78) showed a 4.2 (95% CI, 2.2-8.4) times greater risk of CLABSI compared with patients with 1 CVC after adjusting for CLABSI risk factors. When including APACHE II and CCI scores, multiple CVCs remained an independent risk factor for CLABSI (OR, 3.4 [95% CI, 1.7-6.9]). CONCLUSIONS: Multiple CVCs is an independent risk factor for CLABSI even after adjusting for severity of illness. Adjustment for this risk may be necessary to accurately compare rates between hospitals. PMID- 25111923 TI - Usability and impact of a computerized clinical decision support intervention designed to reduce urinary catheter utilization and catheter-associated urinary tract infections. AB - OBJECTIVE: To evaluate the usability and effectiveness of a computerized clinical decision support (CDS) intervention aimed at reducing the duration of urinary tract catheterizations. DESIGN: Retrospective cohort study. SETTING: Academic healthcare system. PATIENTS: All adult patients admitted from March 2009 through May 2012. INTERVENTION: A CDS intervention was integrated into a commercial electronic health record. Providers were prompted at order entry to specify the indication for urinary catheter insertion. On the basis of the indication chosen, providers were alerted to reassess the need for the urinary catheter if it was not removed within the recommended time. Three time periods were examined: baseline, after implementation of the first intervention (stock reminder), and after a second iteration (homegrown reminder). The primary endpoint was the usability of the intervention as measured by the proportion of reminders through which providers submitted a remove urinary catheter order. Secondary endpoints were the urinary catheter utilization ratio and the rate of hospital-acquired catheter-associated urinary tract infections (CAUTIs). RESULT: The first intervention displayed limited usability, with 2% of reminders resulting in a remove order. Usability improved to 15% with the revised reminder. The catheter utilization ratio declined over the 3 time periods (0.22, 0.20, and 0.19, respectively; P < .001), as did CAUTIs per 1,000 patient-days (0.84, 0.70, and 0.51, respectively; P < .001). CONCLUSIONS: A urinary catheter removal reminder system was successfully integrated within a healthcare system's electronic health record. The usability of the reminder was highly dependent on its user interface, with a homegrown version of the reminder resulting in higher impact than a stock reminder. PMID- 25111924 TI - Preventing the transmission of multidrug-resistant organisms: modeling the relative importance of hand hygiene and environmental cleaning interventions. AB - OBJECTIVE: Hand hygiene and environmental cleaning are essential infection prevention strategies, but the relative impact of each is unknown. This information is important in assessing resource allocation. METHODS: We developed an agent-based model of patient-to-patient transmission-via the hands of transiently colonized healthcare workers and incompletely terminally cleaned rooms-in a 20-patient intensive care unit. Nurses and physicians were modeled and had distinct hand hygiene compliance levels on entry and exit to patient rooms. We simulated the transmission of Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci for 1 year using data from the literature and observed data to inform model input parameters. RESULTS: We simulated 175 parameter-based scenarios and compared the effects of hand hygiene and environmental cleaning on rates of multidrug-resistant organism acquisition. For all organisms, increases in hand hygiene compliance outperformed equal increases in thoroughness of terminal cleaning. From baseline, a 2?1 improvement in terminal cleaning compared with hand hygiene was required to match an equal reduction in acquisition rates (eg, a 20% improvement in terminal cleaning was required to match the reduction in acquisition due to a 10% improvement in hand hygiene compliance). CONCLUSIONS: Hand hygiene should remain a priority for infection control programs, but environmental cleaning can have significant benefit for hospitals or individual hospital units that have either high hand hygiene compliance levels or low terminal cleaning thoroughness. PMID- 25111925 TI - Establishing evidence-based criteria for directly observed hand hygiene compliance monitoring programs: a prospective, multicenter cohort study. AB - OBJECTIVE: Hand hygiene surveillance programs that rely on direct observations of healthcare worker activity may be limited by the Hawthorne effect. In addition, comparing compliance rates from period to period requires adequately sized samples of observations. We aimed to statistically determine whether the Hawthorne effect is stable over an observation period and statistically derive sample sizes of observations necessary to compare compliance rates. DESIGN: Prospective multicenter cohort study. SETTING: Five intensive care units and 6 medical/surgical wards in 3 geographically distinct acute care hospitals. METHODS: Trained observers monitored hand hygiene compliance during routine care in fixed 1-hour periods, using a standardized collection tool. We estimated the impact of the Hawthorne effect using empirical fluctuation processes and F tests for structural change. Standard sample-size calculation methods were used to estimate how many hand hygiene opportunities are required to accurately measure hand hygiene across various levels of baseline and target compliance. RESULTS: Exit hand hygiene compliance increased after 14 minutes of observation (from 56.2% to 60.5%; P < .001) and increased further after 50 minutes (from 60.5% to 66.0%; P < .001). Entry compliance increased after 38 minutes (from 40.4% to 43.4%; P = .005). Between 79 and 723 opportunities are required during each period, depending on baseline compliance rates (range, 35%-90%) and targeted improvement (5% or 10%). CONCLUSIONS: Limiting direct observation periods to approximately 15 minutes to minimize the Hawthorne effect and determining required number of hand hygiene opportunities observed per period on the basis of statistical power calculations would be expected to improve the validity of hand hygiene surveillance programs. PMID- 25111926 TI - A cluster of Mycobacterium wolinskyi surgical site infections at an academic medical center. AB - OBJECTIVE: To study a cluster of Mycobacterium wolinskyi surgical site infections (SSIs). DESIGN: Observational and case-control study. SETTING: Academic hospital. PATIENTS: Subjects who developed SSIs with M. wolinskyi following cardiothoracic surgery. METHODS: Electronic surveillance was performed for case finding as well as electronic medical record review of infected cases. Surgical procedures were observed. Medical chart review was conducted to identify risk factors. A case control study was performed to identify risk factors for infection; Fisher exact or Kruskal-Wallis tests were used for comparisons of proportions and medians, respectively. Patient isolates were studied using pulsed-field gel electrophoresis (PFGE). Environmental microbiologic sampling was performed in operating rooms, including high-volume water sampling. RESULTS: Six definite cases of M. wolinskyi SSI following cardiothoracic surgery were identified during the outbreak period (October 1, 2008-September 30, 2011). Having cardiac surgery in operating room A was significantly associated with infection (odds ratio, 40; P = .0027). Observational investigation revealed a cold-air blaster exclusive to operating room A as well a microbially contaminated, self-contained water source used in heart-lung machines. The isolates were indistinguishable or closely related by PFGE. No environmental samples were positive for M. wolinskyi. CONCLUSIONS: No single point source was established, but 2 potential sources, including a cold-air blaster and a microbially contaminated, self-contained water system used in heart-lung machines for cardiothoracic operations, were identified. Both of these potential sources were removed, and subsequent active surveillance did not reveal any further cases of M. wolinskyi SSI. PMID- 25111927 TI - Translating evidence into practice using a systems engineering framework for infection prevention. PMID- 25111929 TI - Intraoperative stopcock and manifold colonization of newly inserted peripheral intravenous catheters. PMID- 25111930 TI - Electronic monitoring of individual healthcare workers' hand hygiene event rate. PMID- 25111928 TI - High prevalence of reduced chlorhexidine susceptibility in organisms causing central line-associated bloodstream infections. AB - In units that bathe patients daily with chlorhexidine gluconate (CHG), organisms causing central line-associated bloodstream infections (CLABSIs) were more likely to have reduced CHG susceptibility than organisms causing CLABSIs in units that do not bathe patients daily with CHG (86% vs 64%; P = .028). Surveillance is needed to detect reduced CHG susceptibility with widespread CHG use. PMID- 25111931 TI - Anatomic sites of colonization with community-associated methicillin-resistant Staphylococcus aureus. PMID- 25111932 TI - Discordance between novel and traditional surveillance paradigms of ventilator associated pneumonia. PMID- 25111933 TI - Discordance between novel and traditional surveillance definitions for ventilator associated pneumonia: insights and opportunities to improve patient care. PMID- 25111934 TI - Impact of physicians' mindfulness attitudes toward prevention of catheter associated urinary tract infection. PMID- 25111935 TI - A formula for infection control using colonization pressure and compliance rates. PMID- 25111936 TI - Epidemiology of sharps injury and splash exposure in an oncology care center in eastern India. PMID- 25111937 TI - Multidrug-resistant gram-negative bacteria in hematology and oncology. PMID- 25111938 TI - Port-related Aeromonas bacteremia. PMID- 25111939 TI - Tuberculosis infection control: potential benefit of a new rapid tuberculosis test in a human immunodeficiency virus/AIDS reference hospital. PMID- 25111942 TI - Relapse following antithyroid drug therapy for Graves' hyperthyroidism. AB - PURPOSE OF REVIEW: In most patients with hyperthyroidism caused by Graves' disease, antithyroid drug (ATD) therapy is followed by a gradual amelioration of the autoimmune abnormality, but about half of the patients will experience relapse of hyperthyroidism when the ATDs are withdrawn after a standard 1 to 2 years of therapy. This is a major drawback of ATD therapy, and a major concern to patients. We review current knowledge on how to predict and possibly reduce the risk of such relapse. RECENT FINDINGS: Several patient and disease characteristics, as well as environmental factors and duration of ATD therapy, may influence the risk of relapse after ATD withdrawal. Depending on the presence of such factors, the risk of relapse after ATD withdrawal may vary from around 10 to 90%. Risk factors for relapse should be taken into account when choosing between therapeutic modalities in a patient with newly diagnosed disease, and also when discussing duration of ATD therapy. SUMMARY: Prolonged low-dose ATD therapy may be feasible in patients with high risk of relapse, such as children and patients with active Graves' orbitopathy, and in patients with previous relapse who prefer such therapy rather than surgery or radioiodine. PMID- 25111941 TI - Molecular evidence of cryptic diversity in Paracaryophyllaeus (Cestoda: Caryophyllidea), parasites of loaches (Cobitidae) in Eurasia, including description of P. vladkae n. sp. AB - Molecular phylogenetic analysis of an extensive collection of monozoic tapeworms of the genus Paracaryophyllaeus Kulakovskaya, 1961 (Cestoda: Caryophyllidea), parasites of loaches (Cypriniformes: Cobitidae) in Eurasia, has revealed cryptic species diversity within this long-time monotypic genus, especially in the Paracaryophyllaeus gotoi (Motomura, 1927) species complex [syn. Paracaryophyllaeus dubininorum (Kulakovskaya, 1961); type species]. Three independent, well-supported clades were discovered on the basis of molecular data: (i) specimens from Misgurnus anguillicaudatus and Cobitis lutheri from China, Russian Far East and Japan - called herein P. cf. gotoi 1, which may be conspecific with P. gotoi (Motomura, 1927), although in the absence of sequence data for P. gotoi from its type locality (basin of the River Kumkan in Korea), no certain inferences about their identity can currently be made; (ii) specimens from M. anguillicaudatus from China and Japan - P. cf. gotoi 2, which are morphologically indistinguishable from those of P. cf. gotoi 1; and (iii) morphologically distinct tapeworms from the endemic loach Cobitis bilseli from southwestern Turkey (Beysehir Lake), which are described herein as a new species. Paracaryophyllaeus vladkae Scholz, Oros and Aydogdu n. sp. differs from the remaining species of the genus in the following characteristics: the testes begin anterior to the first vitelline follicles (versus posterior), the body is short and robust (versus more elongate and slender), and the scolex is wide, rounded or apically tapered (versus claviform to truncate). Species composition of the genus, host specificity of species and geographical distribution are briefly discussed. PMID- 25111943 TI - Sleeve gastrectomy and Roux En Y gastric bypass: current state of metabolic surgery. AB - PURPOSE OF REVIEW: Roux En Y gastric bypass (RYGB) is considered the bariatric gold standard. Recently, sleeve gastrectomy has gained significant popularity. Early evidence suggests sleeve gastrectomy as a well tolerated and efficacious alternative to RYGB. This article compares RYGB and sleeve gastrectomy by reviewing and summarizing recently published clinical trials. RECENT FINDINGS: Surgery remains the most effective therapy for obese patients meeting criteria. Excess weight loss in short-term follow-up appears similar between RYGB and sleeve gastrectomy. Long-term data on sleeve gastrectomy are limited. RYGB is more effective in producing resolution and remission of type II diabetes mellitus, particularly in patients at high risk for relapse. RYGB and sleeve gastrectomy are similar in their reduction of other obesity-related comorbid conditions with the exception of gastroesophageal reflux disease. RYGB has slightly higher overall morbidity but mortality is similar. SUMMARY: RYGB and sleeve gastrectomy are well tolerated and effective bariatric operations and represent metabolic surgery. More prospective, long-term data are needed. Both procedures benefit specific groups of patients better than the other. Research defining the obese patient's metabolic state and the metabolic response to both operations will ultimately allow physicians to optimally match patient and procedure. PMID- 25111944 TI - How long should patients remain in the supine treatment position after intratympanic dexamethasone injection? AB - OBJECTIVES/HYPOTHESIS: Intratympanic dexamethasone injection (ITDI) is a widely accepted treatment for patients with sudden hearing loss. We investigated the appropriate patient wait time in the supine treatment position after ITDI. STUDY DESIGN: Prospective study. METHODS: In an in vivo animal study, 24 mice were injected intratympanically with dexamethasone. Perilymphatic fluid was sampled at 5, 10, 15, 20, 25, and 30 minutes postinjection. The dexamethasone concentration was analyzed using high-performance liquid chromatography. In a separate prospective clinical study, 79 patients with refractory sudden hearing loss underwent intratympanic injection. After the injection, patients remained in the supine position with the head rotated 45 degrees to the unaffected side. Patients were divided into two groups according to the wait time in this treatment position postinjection: 30 minutes (n = 47) and 10 minutes (n = 32). Final hearing assessments were conducted 2 months after salvage treatment. RESULTS: In the in vivo animal study, the perilymphatic concentration of dexamethasone showed no significant increase after 10 minutes. In the clinical setting, hearing improvement according to Siegel's criteria was similar in the 30 minute (14/47) and 10-minute (10/32) groups (P = 0.999). No significant differences in relative hearing gain was observed between the two groups (13.80 +/- 19.9 dB and 12.57 +/- 14.9 dB, respectively; P = 0.766). CONCLUSION: We suggest that 10 minutes is a sufficient time to remain in the supine treatment position after ITDI in patients with sudden hearing loss. LEVEL OF EVIDENCE: N/A. PMID- 25111945 TI - Transient osteoporosis of pregnancy of the bilateral hips in twin gestation: a case series. AB - Transient osteoporosis of pregnancy has been described as a rare, self-limiting disease of unclear etiology that presents as severe pain, which typically affects pregnant women in their third trimester. We describe 3 cases of primigravid pregnant women with twin gestation who reported unilateral hip pain and who were diagnosed with transient osteoporosis of pregnancy of the hip by magnetic resonance imaging. These women were advised to undergo limited weight bearing and activity modification to minimize the risk of fracture. Each patient was able to proceed through her pregnancy, delivery, and postpartum course without complication, with symptom resolution, and return to unrestricted activity. PMID- 25111946 TI - Single leg squat test and its relationship to dynamic knee valgus and injury risk screening. AB - BACKGROUND: Lower extremity injuries are common in athletes. Valid tests to assess for risk of injury that are easily performed during a preparticipation sports physical examination are lacking. Two-dimensional (2D) analysis of the drop-jump test can identify athletes at risk, but it is too expensive and cumbersome to use in this setting. OBJECTIVE: To identify if those who perform a "positive"(abnormal postures) single leg squat (SLS) test also exhibit greater "dynamic valgus" on the 2D drop-jump test. Our secondary purpose was to assess whether group differences in gender, age, or body mass index are evident between those who exhibit a positive SLS test result versus a negative SLS test result. Also, we wanted to determine any gender differences with the 2D drop-jump test. DESIGN: A cross-sectional study. SETTING: Private practice, preparticipation sports physical examinations. PARTICIPANTS: A total of 142 middle school and high school athletes. METHODS: Participants performed a SLS test and a drop-jump test during their preparticipation sports physical examination. Individuals were partitioned into groups based on the outcome of their SLS test (positive SLS group versus negative SLS group). Independent sample t-tests were used to evaluate SLS group differences in the drop-jump test, age, and body mass index, and the chi(2) test was used to evaluate SLS group differences in gender (P <= .05). MAIN OUTCOME MEASUREMENTS: The SLS test and drop-jump test. RESULTS: Seventy-three of the 142 athletes (51%) had a positive SLS test result, whereas 69 athletes (49%) had a negative SLS test result. Individuals in the positive SLS group had a significantly lower knee-hip ratio), indicative of greater dynamic knee valgus, than did those in the negative SLS group (P = .02). Individual characteristics between SLS groups including gender, age, and body mass index were similar. CONCLUSION: The SLS test is a reasonable tool to use in preparticipation sports physical examinations to assess for dynamic knee valgus and the potential risk of lower extremity injury. PMID- 25111947 TI - Detection of DNA damage in peripheral blood mononuclear cells from pancreatic cancer patients. AB - DNA repair is a key mechanism in maintaining genomic stability: repair deficiencies increase DNA damage and mutations that lead to several diseases, including cancer. We extracted DNA from peripheral blood mononuclear cells (PBMCs) of 48 pancreatic adenocarcinoma cases and 48 healthy controls to determine relative levels of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage by QPCR. All participants were never smokers and between the ages of 60 and 69. Average levels among cases were compared to controls using a rank sum test, and logistic regression adjusted for potential confounding factors (age, sex, and diabetes mellitus). Cases had less DNA damage, with a significant decrease in mtDNA damage (P-value = 0.03) and a borderline significant decrease in nDNA damage (P = 0.08). Across samples, we found mtDNA abundance was higher among non-diabetics compared to diabetics (P = 0.04). Our results suggest that patients with pancreatic adenocarcinoma have less DNA damage in their PBMCs, and that having diabetes, a known pancreatic cancer risk factor, is associated with lower levels of mtDNA abundance. PMID- 25111949 TI - Transposition of the left renal vein for the treatment of nutcracker syndrome in children: a short-term experience. AB - BACKGROUND: Nutcracker syndrome is caused by compression of the left renal vein between the superior mesenteric artery and the aorta. Invasive surgical intervention for this pathologic entity is controversial, particularly in the pediatric population. We aim to describe our early clinical and operative experience with such patients. METHODS: We report 3 cases of pediatric patients undergoing successful left renal vein transposition for the treatment of nutcracker syndrome. RESULTS: All 3 patients were female (age 9-17 years) and presented with a mean of 11.7 months of abdominal or left flank pain requiring chronic narcotic analgesia. Initial clinical presentations were associated with either hematuria or proteinuria. Diagnosis of nutcracker syndrome was supported in each case by an elevated renocaval pressure gradient and/or axial imaging demonstrating mesoaortic compression of the left renal vein. All patients underwent open surgical repair, which included left renal vein transposition, liberation of the ligament of Treitz and associated adhesions, as well as excision of periaortic nodal tissue (mean hospital length of stay 5.7 days). After mean follow-up of 13 months, all patients report complete resolution of symptoms and hematuria/proteinuria. CONCLUSIONS: Transposition of the left renal vein is a safe and effective treatment for nutcracker syndrome in appropriately selected pediatric patients. Further experience and long-term follow-up are warranted to better evaluate the sustained efficacy of this procedure in this unique patient population. PMID- 25111948 TI - White-matter relaxation time and myelin water fraction differences in young adults with autism. AB - BACKGROUND: Increasing evidence suggests that autism is associated with abnormal white-matter (WM) anatomy and impaired brain 'connectivity'. While myelin plays a critical role in synchronized brain communication, its aetiological role in autistic symptoms has only been indirectly addressed by WM volumetric, relaxometry and diffusion tensor imaging studies. A potentially more specific measure of myelin content, termed myelin water fraction (MWF), could provide improved sensitivity to myelin alteration in autism. METHOD: We performed a cross sectional imaging study that compared 14 individuals with autism and 14 age- and IQ-matched controls. T 1 relaxation times (T 1), T 2 relaxation times (T 2) and MWF values were compared between autistic subjects, diagnosed using the Autism Diagnostic Interview - Revised (ADI-R), with current symptoms assessed using the Autism Diagnostic Observation Schedule (ADOS) and typical healthy controls. Correlations between T 1, T 2 and MWF values with clinical measures [ADI-R, ADOS, and the Autism Quotient (AQ)] were also assessed. RESULTS: Individuals with autism showed widespread WM T 1 and MWF differences compared to typical controls. Within autistic individuals, worse current social interaction skill as measured by the ADOS was related to reduced MWF although not T 1. No significant differences or correlations with symptoms were observed with respect to T 2. CONCLUSIONS: Autistic individuals have significantly lower global MWF and higher T 1, suggesting widespread alteration in tissue microstructure and biochemistry. Areas of difference, including thalamic projections, cerebellum and cingulum, have previously been implicated in the disorder; however, this is the first study to specifically indicate myelin alteration in these regions. PMID- 25111950 TI - Isolated dissecting aneurysms of the abdominal aorta and the superior mesenteric artery. A case report and literature review. AB - Supracoeliac abdominal aortic dissections are rare and require complex interventions for repair. Superior mesenteric artery (SMA) dissections are also rare and even less frequently reported to involve aneurysmal change. We present the case of a 65-year-old man with a dissecting supracoeliac aortoiliac aneurysm and a separate dissecting aneurysm of the SMA The surgical intervention performed and a review of the literature on the management of SMA dissection in the endovascular era are presented. PMID- 25111951 TI - Antiinflammatory properties of the stem-bark of Anopyxis klaineana and its major constituent, methyl angolensate. AB - Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) is one of the reputed West African folkloric medicines that has never been investigated for its pharmacological effects or phytochemical constituents. In the present study, the antiinflammatory properties of the stem-bark extracts were evaluated using the carrageenan-induced paw oedema model in chicks. The petroleum ether, ethyl acetate and methanol extracts all showed a time and dose-dependent antiinflammatory effect over the 5-h observation period. Phytochemical analysis of the most active extract (methanol extract) yielded the principal constituent that was identified as methyl angolensate through extensive spectroscopic and X ray analysis studies. Although slightly less potent (ED50 , 4.05 +/- 0.0034 mg/kg, orally) than the positive control, diclofenac (ED50 , 2.49 +/- 0.023, intraperitoneally n = 5), this first ever compound isolated from A. klaineana showed promising antiinflammatory activity that may account to some of the reported medicinal uses of the plant. PMID- 25111952 TI - Importance of diameter control on selective synthesis of semiconducting single walled carbon nanotubes. AB - The coexistence of semiconducting and metallic single-walled carbon nanotubes (SWNTs) during synthesis is one of the major bottlenecks that prevent their broad application for the next-generation nanoelectronics. Herein, we present more understanding and demonstration of the growth of highly enriched semiconducting SWNTs (s-SWNTs) with a narrow diameter distribution. An important fact discovered in our experiments is that the selective elimination of metallic SWNTs (m-SWNTs) from the mixed arrays grown on quartz is diameter-dependent. Our method emphasizes controlling the diameter distribution of SWNTs in a narrow range where m-SWNTs can be effectively and selectively etched during growth. In order to achieve narrow diameter distribution, uniform and stable Fe-W nanoclusters were used as the catalyst precursors. About 90% of as-prepared SWNTs fall into the diameter range 2.0-3.2 nm. Electrical measurement results on individual SWNTs confirm that the selectivity of s-SWNTs is ~95%. The present study provides an effective strategy for increasing the purity of s-SWNTs via controlling the diameter distribution of SWNTs and adjusting the etchant concentration. Furthermore, by carefully comparing the chirality distributions of Fe-W-catalyzed and Fe-catalyzed SWNTs under different water vapor concentrations, the relationship between the diameter-dependent and electronic-type-dependent etching mechanisms was investigated. PMID- 25111953 TI - Inverse effect of mucinous component on survival in stage III colorectal cancer. AB - BACKGROUND: Although mucinous adenocarcinoma (MAC) is has been recognized as a separate entity in colorectal cancer (CRC), adenocarcinoma with a mucinous component (ACM) remains poorly understood. METHODS: The association of MAC and ACM with disease-free survival (DFS) and overall survival (OS) was examined using the Cox proportional hazard model in 425 consecutive stage III CRCs. RESULTS: Compared with conventional adenocarcinoma (CAC), patients with MAC exhibited independently worse DFS (hazard ratio [HR], 2.64; 95% CI, 1.21-5.80; P = 0.014) and OS (HR, 3.56; 95% CI, 1.53-8.30; P = 0.003). Unexpectedly, ACM was significantly associated with worse OS than CAC (P = 0.002), despite having a similar DFS to CAC. Further, ACM patients after recurrence exhibited significantly worse OS than CAC patients (P < 0.001), similar to MAC. CONCLUSIONS: Although ACM is similar to CAC with regard to estimated risk of recurrence, the outcome is extremely poor once recurrence occurs and is identical to MAC; one of the most aggressive phenotypes of stage III CRC. Thus, both MAC and ACM are adverse prognostic factors for OS. PMID- 25111954 TI - Surveillance colonoscopy in elderly patients: a retrospective cohort study. AB - IMPORTANCE: The risks and benefits of surveillance colonoscopy in elderly patients have not been well characterized. OBJECTIVE: To investigate the relative impact of surveillance colonoscopy in elderly patients compared with a reference cohort. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study from 2001 through 2010 of patients 50 years and older undergoing surveillance colonoscopy for a history of colorectal cancer (CRC) or adenomatous polyps at an integrated health care system in southern California. Patients were followed up from the surveillance examination until CRC diagnosis, death, disenrollment, IBD diagnosis, or study end date (December 31, 2010). MAIN OUTCOMES AND MEASURES: The primary outcome measure was incidence of CRC detected following surveillance colonoscopy. The secondary outcome was risk of procedure defined as postprocedure hospitalization within 30 days. Cox regression and multivariable logistic regression analyses were used to determine the impact of age on CRC incidence on surveillance examination as well as postprocedure hospitalization, respectively. RESULTS: The study cohort included 4834 elderly patients (age >=75 years; 55.8% male) (median surveillance age, 79 years) and 22 929 individuals in the reference group (age 50-74 years; 57.7% male) (median surveillance age, 63 years). A total of 373 cancers were detected following surveillance colonoscopy (368 in the reference group and 5 among the elderly patients). There were a total of 711 postprocedure hospitalizations (184 in the reference group and 527 among the elderly patients). The CRC incidence among elderly patients undergoing surveillance was 0.24 per 1000 person-years vs 3.61 per 1000 person-years in the reference population (P < .001). In Cox regression analysis, the hazard ratio for CRC in the elderly patients compared with the reference group was 0.06 (95% CI, 0.02-0.13) (P < .001) after adjusting for comorbid illness, sex, and race/ethnicity. In logistic regression analysis, age 75 years and older was independently associated with increased risk of postprocedure hospitalization (adjusted odds ratio, 1.28 [95% CI, 1.07-1.53]; P = .006). Charlson score of 2 was also independently associated with increased risk of postprocedure hospitalization (adjusted odds ratio, 2.54 [95% CI, 2.06-3.14]; P < .001). CONCLUSIONS AND RELEVANCE: A low incidence of CRC and relatively high rate of postprocedure hospitalization were found among elderly patients undergoing surveillance colonoscopy. Recommendations for ongoing surveillance in the elderly population should take into consideration the impact of comorbid illness and increasing age on the anticipated risks and benefits of colonoscopy. PMID- 25111955 TI - Family dynamics and young children's sibling victimization. AB - This research examines how family dynamics like interparental conflict, family violence, and quality of parenting are associated with young children's experiences of sibling victimization. We use nationally representative data from interviews with caregivers of 1,726 children aged 2 to 9 years of age. We hypothesized different family dynamics predictors for a composite of common types of sibling victimization (property, psychological, and mild physical aggression) in comparison to severe physical sibling victimization (victimization that includes physical aggression with a weapon and/or injury). Multinomial regression results showed that sibling victimization in general was associated with negative family dynamics but that children in the severe group had even less parental warmth, poor parental supervision, and greater exposure to interparental conflict and family violence than children in the common types victimization group. Different aspects of family dynamics contribute to sibling victimization, but possibly in different ways and with different consequences. The findings underscore the importance of a family systems theory approach to clinical and intervention work. PMID- 25111956 TI - Shared possible selves, other-focus, and perceived wellness of couples with prostate cancer. AB - Shared possible selves are associated with better well-being in couples through their engagement in and enjoyment of collaboration (Schindler, Berg, Butler, Fortenberry, & Wiebe, 2010). The present study sought to address which partner's other-focus accounted for this sharedness in possible selves and how the individual and dyadic configurations of other-focused selves relate to health and well-being (i.e., perceived wellness) in an important health context for adult couples-prostate cancer. Sixty-one men diagnosed with prostate cancer and their wives rated their own subjective physical health and well-being and listed possible selves. Possible selves were reliably coded for the inclusion of the other (i.e., other-focus), either with the other as the subject or communal in content. Regression analysis showed that wives' other-focus, not husbands', explained variance in shared selves. A Bayesian actor-partner interdependence model (APIM) of both partners' other-focus and interaction between the 2 revealed a pattern that differed by partner. The association between husband other-focus and his perceived wellness was negative for husbands whose wives were low in other-focus and not significant for husbands with highly other-focused wives. Women's sense of perceived wellness did not relate to either partner's other focus. Results support the notion that shared possible selves may be shared unequally in couples facing chronic illness and suggest the importance of considering both partners' other-focus to understand perceived wellness. Findings may point to more general processes of relational adaptation to major life stressors such as prostate cancer. PMID- 25111957 TI - Oleanolic acid co-administration alleviates ethanol-induced hepatic injury via Nrf-2 and ethanol-metabolizing modulating in rats. AB - Alcoholic liver disease (ALD) is one of the leading causes of death in the world. Oxidative stress plays an important role in the pathogenesis of alcohol-induced liver injury. Our previous results have found that oleanolic acid (OA), a liver protective agent, plays a potent antioxidant activity in hepatocyte. In the present study, the protective effects of OA co-administration on ethanol-induced oxidative injury in rats were investigated through detecting hepatic histopathology, antioxidant enzymes, ethanol metabolic enzymes and inflammatory factors. Preventions of ethanol-induced oxidative injury by OA were reflected by markedly decreased serum activities of AST, ALT and significantly increased the hepatic ATP level. In addition, the increase of the hepatic TG content, MDA level and the decrease of hepatic GSH level, SOD activity, CAT activity induced by ethanol were significantly inhibited by OA co-administration. Furthermore, OA could also elevate the protein expressions and nuclear translocation of antioxidant transcription factor Nrf-2 and then up-regulated antioxidant enzymes expressions of HO-1, SOD-1 and GR. Moreover, OA co-administration can significantly reduce the activity and expressions of CYP2E1 and ADH, which has characteristic of generation ROS mediated oxidative stress and acetaldehyde respectively. Furthermore, OA co-administration could inhibition of the generation of inflammatory factors TNF-alpha and IL-6. Those above results indicated that OA co-administration can protect rats against ethanol-induced liver injury by induction Nrf-2 related antioxidant to maintain redox balance and modulating the ethanol-metabolizing and inflammatory pathway. PMID- 25111958 TI - Ovarian insufficiency and pubertal development after hematopoietic stem cell transplantation in childhood. AB - BACKGROUND: Ovarian insufficiency (OI) and infertility are common and devastating late effects of cancer treatment and hematopoietic stem cell transplantation (HSCT). In children, gonadal insufficiency may subsequently lead to abnormal pubertal development. The aim of this study was to assess the cumulative incidence of OI and the need for hormonal induction of pubertal development after HSCT in childhood. We additionally assessed HSCT-related risk factors for OI. PROCEDURES: A single center cohort study was undertaken of female patients transplanted during childhood, surviving at least 2 years post-HSCT and who were at least 10 years old at initiation of the study. Of 141 eligible patients, 109 were included and hormone levels and clinical data of these patients during follow-up were collected. Risk factors for OI were analyzed by multivariate Cox regression analysis. RESULTS: Cumulative incidence of OI was 56% at a median follow-up of 7.2 years. Eight patients, initially diagnosed with OI, showed recovery of ovarian function over time. Hormonal induction of puberty was necessary in 44% of females who were pre-pubertal or pubertal at HSCT. In multivariate analysis, more advanced pubertal stage at HSCT was associated with OI. We found a trend for an association of busulfan with OI in patients conditioned with chemotherapy only. CONCLUSIONS: The incidence of OI after HSCT was high and associated with more advanced pubertal stage at HSCT. Almost half of the females who were pre-pubertal or pubertal at HSCT required hormonal induction of pubertal development. PMID- 25111959 TI - Pharmacokinetic profile and first preliminary clinical evaluation of bendamustine in Taiwanese patients with heavily pretreated indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. AB - Prior studies found bendamustine is efficacious in patients with indolent B-cell non-Hodgkin lymphoma (NHL). To date, no studies have reported the efficacy of bendamustine in a Chinese population. This multicentre phase II trial evaluated the pharmacokinetics (PK), safety and efficacy of bendamustine monotherapy in Chinese patients in Taiwan with pretreated indolent B-cell NHL or mantle cell lymphoma (MCL). For PK assessments, patients were randomized (n = 16; 11 with indolent B-cell NHL and five with MCL) to 90 or 120 mg/m(2) of bendamustine for the first cycle. Plasma levels of bendamustine and its two metabolites were analyzed. For efficacy and safety evaluations, bendamustine 120 mg/m(2) was given to all patients every 3 weeks starting at cycle 2 for a minimum of a total of six cycles. The median age of patients was 61.7 years, and the majority were men (75%). The median number of prior treatments was 4 (range, 1-9 regimens), and all patients were previously treated with rituximab. Bendamustine plasma concentration peaked near the end of infusion and was rapidly eliminated with a mean elimination half-life (t(1/2)) of 0.67-0.8 h. Of the evaluable patients (n = 14), the overall response rate was 78.6%, including 7.2% of patients having a complete response. Mean progression-free survival was 27.5 weeks. The most common grade 3-4 adverse events were leucopenia (56.3%), neutropenia (56.3%) and thrombocytopenia (25%). In conclusion, bendamustine was efficacious and well tolerated in Taiwanese patients with indolent NHL and MCL with a similar PK profile to that of other populations. PMID- 25111960 TI - Emission-tunable CuInS2/ZnS quantum dots: structure, optical properties, and application in white light-emitting diodes with high color rendering index. AB - Synthesis and application of CuInS2/ZnS core/shell quantum dots (QDs) with varying [Cu]/[In] ratios were conducted using a stepwise solvothermal route. CuInS2 (CIS) core QDs with varying [Cu]/[In] ratios exhibited deep-red emissions result from donor-acceptor pair recombination. The absorption and emission band gap of the CuInS2 QDs increased with the decrease in Cu content. The emission bands of the CuInS2/ZnS were tuned from 550 to 616 nm by controlling the [Cu]/[In] ratio after coating ZnS layer. The CIS QDs model was developed to elucidate the synthesized crystal structure and photoluminescence of the QDs with various [Cu]/[In] ratios. Temperature-dependent photoluminescence spectra of the CIS/ZnS QDs were also investigated. The temperature dependency of the photoluminescence energy and intensity for various CIS/ZnS QDs were studied from 25 to 200 degrees C. Efficient white light-emitting diodes with high color rendering index values (Ra = 90) were fabricated using CIS/ZnS QDs as color converters in combination with green light-emitting Ba2SiO4:Eu(2+) phosphors and blue light-emitting diodes. PMID- 25111961 TI - Systematic review of pharmacological treatments for depressive symptoms in Huntington's disease. AB - BACKGROUND: Depressive symptoms are common in Huntington's disease (HD), profoundly affect quality of life, and predict suicidal ideation. However, no recent review of antidepressant treatment in HD has been published. METHODS: We performed a PRISMA systematic review of HD studies, which used a recognized antidepressant and measured change in depressive symptoms using a validated psychiatric scale. Controlled trials, uncontrolled trials, observational studies, and case series were included. RESULTS: Eleven studies were included, totalling 190 patients. One study examined venlafaxine, one fluoxetine, one citalopram, one atomoxetine, one modafinil, one lithium, and five antipsychotics. No studies were of adequate duration, size, or outcome, and no controlled trial in a depressed population produced a positive result. CONCLUSIONS: Inadequate evidence exists to guide antidepressant treatment in HD. Further research is needed to assess antidepressant efficacy and to examine whether treatment of depression represents a modifiable target for the high suicide rate in HD. PMID- 25111962 TI - Regulatory decision-making: are we getting it right? PMID- 25111963 TI - Development of a new benzylating reagent spontaneously releasing benzyl cation equivalents at room temperature. AB - A new O-benzylating reagent, that is, 4-(4,6-diphenoxy-1,3,5-triazin-2-yl)-4 benzylmorpholinium trifluoromethanesulfonate (DPT-BM), has been developed. Benzyl cation equivalents are generated from DPT-BM by dissolving the compound in a solvent at room temperature under non-acidic conditions. The benzylation of various alcohols by using a combination of DPT-BM and magnesium oxide provided the benzyl ethers in good yields. PMID- 25111964 TI - SLaP mapper: a webserver for identifying and quantifying spliced-leader addition and polyadenylation site usage in kinetoplastid genomes. AB - The Kinetoplastida are a diverse and globally distributed class of free-living and parasitic single-celled eukaryotes that collectively cause a significant burden on human health and welfare. In kinetoplastids individual genes do not have promoters, but rather all genes are arranged downstream of a small number of RNA polymerase II transcription initiation sites and are thus transcribed in polycistronic gene clusters. Production of individual mRNAs from this continuous transcript occurs co-transcriptionally by trans-splicing of a ~39 nucleotide capped RNA and subsequent polyadenylation of the upstream mRNA. SLaP mapper (Spliced-Leader and Polyadenylation mapper) is a fully automated web-service for identification, quantitation and gene-assignment of both spliced-leader and polyadenylation addition sites in Kinetoplastid genomes. SLaP mapper only requires raw read data from paired-end Illumina RNAseq and performs all read processing, mapping, quality control, quantification, and analysis in a fully automated pipeline. To provide usage examples and estimates of the quantity of sequence data required we use RNAseq obtained from two different library preparations from both Trypanosoma brucei and Leishmania mexicana to show the number of expected reads that are obtained from each preparation type. SLaP mapper is an easy to use, platform independent webserver that is freely available for use at http://www.stevekellylab.com/software/slap. Example files are provided on the website. PMID- 25111965 TI - The revolution of whole genome sequencing to study parasites. AB - Genome sequencing has revolutionized the way in which we approach biological research from fundamental molecular biology to ecology and epidemiology. In the last 10 years the field of genomics has changed enormously as technology has improved and the tools for genomic sequencing have moved out of a few dedicated centers and now can be performed on bench-top instruments. In this review we will cover some of the key discoveries that were catalyzed by some of the first genome projects and discuss how this field is developing, what the new challenges are and how this may impact on research in the near future. PMID- 25111966 TI - Characterization of recombinant malarial RecQ DNA helicase. AB - RecQ DNA gene of multi-drug resistant Plasmodium falciparum K1 (PfRecQ1) was cloned, and the recombinant C-terminal-decahistidine-tagged PfRecQ1 was expressed in Escherichia coli. The purified enzyme could efficiently unwind partial duplex DNA substrate in a 3' to 5' direction. The malarial RecQ1 could not unwind substrates with both 5' and 3' overhangs, those with a 5' overhang, or blunt ended DNA duplexes. Unwinding of DNA helicase activity was driven by the hydrolysis of ATP. The drug inhibitory effects of six compounds indicated that only doxorubicin and daunorubicin could inhibit the unwinding activity. PMID- 25111968 TI - Development, validation and characterization of a novel mouse model of Adynamic Bone Disease (ABD). AB - The etiology of Adynamic Bone Disease (ABD) is poorly understood but the hallmark of ABD is a lack of bone turnover. ABD occurs in renal osteodystrophy (ROD) and is suspected to occur in elderly patients on long-term anti-resorptive therapy. A major clinical concern of ABD is diminished bone quality and an increased fracture risk. To our knowledge, experimental animal models for ABD other than ROD-ABD have not been developed or studied. The objectives of this study were to develop a mouse model of ABD without the complications of renal ablation, and to characterize changes in bone quality in ABD relative to controls. To re-create the adynamic bone condition, 4-month old female Col2.3Deltatk mice were treated with ganciclovir to specifically ablate osteoblasts, and pamidronate was used to inhibit osteoclastic resorption. Four groups of animals were used to characterize bone quality in ABD: Normal bone controls, No Formation controls, No Resorption controls, and an Adynamic group. After a 6-week treatment period, the animals were sacrificed and the bones were harvested for analyses. Bone quality assessments were conducted using established techniques including bone histology, quantitative backscattered electron imaging (qBEI), dual energy X-ray absorptiometry (DXA), microcomputed tomography (microCT), and biomechanical testing. Histomorphometry confirmed osteoblast-related hallmarks of ABD in our mouse model. Bone formation was near complete suppression in the No Formation and Adynamic specimens. Inhibition of bone resorption in the Adynamic group was confirmed by tartrate-resistant acid phosphatase (TRAP) stain. Normal bone mineral density and architecture were maintained in the Adynamic group, whereas the No Formation group showed a reduction in bone mineral content and trabecular thickness relative to the Adynamic group. As expected, the No Formation group had a more hypomineralized profile and the Adynamic group had a higher mean mineralization profile that is similar to suppressed bone turnover in human. This data confirms successful replication of the adynamic bone condition in a mouse without the complication of renal ablation. Our approach is the first model of ABD that uses pharmacological manipulation in a transgenic mouse to mimic the bone cellular dynamics observed in the human ABD condition. We plan to use our mouse model to investigate the adynamic bone condition in aging and to study changes to bone quality and fracture risk as a consequence of over-suppressed bone turnover. PMID- 25111970 TI - Outcomes in operative management of pancreatic cancer. AB - Pancreatic cancer is a highly lethal malignancy that often presents at an advanced stage. Surgical resection can prolong survival and offers the only potential for cure. However, pancreatectomy is associated with significant morbidity and mortality. This article reviews perioperative outcomes, post resection long-term survival, and innovations in the surgical management of pancreatic cancer. PMID- 25111971 TI - The use of 3D power Doppler ultrasound in the quantification of blood vessels in uterine fibroids: feasibility and reproducibility. AB - BACKGROUND: To evaluate the interobserver agreement and discriminating value of three-dimensional power Doppler ultrasound (3D PDUS) in patients with fibroids. METHODS: An observational prospective cohort study in 19 patients with fibroids. 3D PDUS was performed by one examiner and evaluated by three independent examiners in order to evaluate various vascular parameters: vascular index (VI), flow index, and vascular flow index of the fibroid, the vascular capsule and of its highest vascular area, using both manual and automatic contour modes. The intraclass correlation coefficient and discriminating values were calculated. The correlation between VI and volume was studied using Kendall's Tau test. RESULTS: In the manual contour mode, the VIs of the fibroid and of the vascular capsule had the highest interobserver agreements (intraclass correlation coefficients of 0.89 and 0.87, respectively). Both parameters seem to have good discriminating values, given the large range of these parameters between different fibroids, independent of their volume. The vascularity of the fibroid and capsule was related. VI was not related to the volume of the fibroid. CONCLUSIONS: VI assessed using 3D PDUS is a reproducible parameter in the assessment of fibroid vascularization with discriminating abilities. Additional studies are needed to further evaluate its validity and clinical relevance. PMID- 25111972 TI - Response to "'Everybody's plastic": so what?'. PMID- 25111969 TI - Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen inhalation and chemotherapy by implantable resonator-based oximetry. AB - Hypoxia is a critical hallmark of glioma, and significantly compromises treatment efficacy. Unfortunately, techniques for monitoring glioma pO2 to facilitate translational research are lacking. Furthermore, poor prognosis of patients with malignant glioma, in particular glioblastoma multiforme, warrant effective strategies that can inhibit hypoxia and improve treatment outcome. EPR oximetry using implantable resonators was implemented for monitoring pO2 in normal cerebral tissue and U251 glioma in mice. Breathing carbogen (95% O2 + 5% CO2 ) was tested for hyperoxia in the normal brain and glioma xenografts. A new strategy to inhibit glioma growth by rationally combining gemcitabine and MK 8776, a cell cycle checkpoint inhibitor, was also investigated. The mean pO2 of left and right hemisphere were ~56-69 mmHg in the normal cerebral tissue of mice. The mean baseline pO2 of U251 glioma on the first and fifth day of measurement was 21.9 +/- 3.7 and 14.1 +/- 2.4 mmHg, respectively. The mean brain pO2 including glioma increased by at least 100% on carbogen inhalation, although the response varied between the animals over days. Treatment with gemcitabine + MK 8776 significantly increased pO2 and inhibited glioma growth assessed by MRI. In conclusion, EPR oximetry with implantable resonators can be used to monitor the efficacy of carbogen inhalation and chemotherapy on orthotopic glioma in mice. The increase in glioma pO2 of mice breathing carbogen can be used to improve treatment outcome. The treatment with gemcitabine + MK-8776 is a promising strategy that warrants further investigation. PMID- 25111973 TI - "Everybody's plastic": so what? PMID- 25111974 TI - Prenatal melamine exposure induces impairments of spatial cognition and hippocampal synaptic plasticity in male adolescent rats. AB - Our previous studies showed that chronic melamine exposure could affect hippocampal synaptic plasticity and impair learning and memory on adult rats. In this study, we investigated whether prenatal melamine exposure (PME) induced cognitive deficits and impairment of synaptic plasticity in postnatal offspring. An animal model was produced by melamine exposure throughout gestational period with 400mg/kg/day, while male offspring rats were employed. Rats' performance in Morris water maze (MWM) was tested to evaluate learning and memory. To examine the variations of paired-pulse facilitation (PPF) and synaptic plasticity, field excitatory postsynaptic potentials (fEPSPs) were recorded in hippocampal CA1 by stimulating Schaffer collaterals path. The result showed that PME probably impaired spatial learning and memory. The fEPSPs amplitudes of LTP were much lower and the PPF ratio was significantly higher in PME group than controls. These data suggested that PME impaired hippocampal synaptic function, which was partly involved in spatial cognition impairments. PMID- 25111976 TI - Effect of extended pi-conjugation structure of donor-acceptor conjugated copolymers on the photoelectronic properties. AB - New donor-acceptor conjugated copolymers based on alkylthienylbenzodithiophene (BDTT) and alkoxynaphthodithiophene (NDT) have been synthesized and compared with their benzo[1,2-b:4,5-b']dithiophene (BDT)-based analogues to investigate the effect of the extended pi conjugation of the polymer main chain on the physicochemical properties of the polymers. A systematic investigation into the optical properties, energy levels, field-effect transistor characteristics, and photovoltaic characteristics of these polymers was conducted. Both polymers demonstrated enhanced photovoltaic performance and increased hole mobility compared with the BDT-based analogue. However, the BDTT-based polymer (with pi conjugation extension perpendicular to main chain) gave the highest power conversion efficiency of 5.07% for the single-junction polymer solar cell, whereas the NDT-based polymer (with pi-conjugation extension along the main chain) achieved the highest hole mobility of approximately 0.1 cm(2) V(-1) s(-1) based on the field-effect transistor; this indicated that extending the pi conjugation in different orientations would have a significant influence on the properties of the resulting polymers. PMID- 25111975 TI - Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs. AB - To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH) and levetiracetam (LEV). For VPA, histopathology was the most sensitive parameter, showing effects already at 60MUM. For CBZ, morphology and MA were the most sensitive parameters, showing effects at 180MUM. For ETH, all endpoints showed similar sensitivity (6.6mM), whereas MA was the most sensitive parameter for LEV (40mM). Inclusion of kinetics did not alter the absolute ranking of the compounds, but the relative potency was changed considerably. Taking all together, this demo-case study showed that inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay, contribute to the elucidation of the mode of toxic action and to a better definition of the applicability domain of ZET. PMID- 25111977 TI - Behavioral side effects of pediatric acute lymphoblastic leukemia treatment: the role of parenting strategies. AB - BACKGROUND: Behavioral and emotional difficulties are a recognised side effect of childhood acute lymphoblastic leukemia (ALL) treatment. Modifiable factors, such as parenting strategies, may be an appropriate target for interventions to assist families with managing their child's behavior, potentially leading to improved psychosocial and clinical outcomes. This study examined whether parenting strategies are associated with child behavioral and emotional problems in a pediatric oncology context, with the aim of establishing whether parenting is a potential modifiable target for psychosocial intervention. PROCEDURE: Participants included 73 parents of children aged 2-6 years who were either (i) in the maintenance phase of treatment for ALL at the Royal Children's Hospital Children's Cancer Centre, Melbourne (N = 43), or (ii) had no major medical history (healthy control group) (N = 30). Participants completed psychometrically validated questionnaires that assessed parenting strategies and child emotional and behavioral problems. RESULTS: Results revealed that the ALL group parents reported higher lax parenting and more spoiling and bribing of their child than the healthy control group. Results from regression models indicated that, after controlling for the significant contribution of illness status and child age on child emotional and behavioral difficulties, parental laxness and parental overprotection were significantly associated with child emotional and behavioral difficulties. CONCLUSIONS: Supporting parents to minimise sub-optimal parenting strategies, particularly lax parenting, may offer a fruitful avenue for future research directed toward modifiable factors associated with managing child emotional and behavioral problems in a pediatric oncology context. PMID- 25111978 TI - Reduction of physiological effects in fNIRS waveforms for efficient brain-state decoding. AB - This paper presents a methodology for online estimation of brain activities with reduction in the effects of physiological noises in functional near-infrared spectroscopy signals. The input-output characteristics of a hemodynamic response are modeled as an autoregressive moving average model together with exogenous physical signals (i.e., ARMAX). In contrast to the fixed design matrix in the conventional general linear model, the proposed model incorporates the temporal variations in the experimental paradigm as well as in the hemodynamics. The performance of the proposed method has been tested by using box-car type functions followed by individual tapping tasks. The results and their significance were verified using t-statistics indicating that ARMAX seems to be better able to track/reveal the hemodynamic response. Also, online brain activation maps were generated for localizing brain activities. Experimental results are compared with those of the existing conventional GLM-based method. PMID- 25111979 TI - alpha-Synuclein rs356219 polymorphisms in patients with Gaucher disease and Parkinson disease. AB - Mutations in beta-glucocerebrosidase, the genetic defect in Gaucher disease (GD), are an important susceptibility factor for Parkinson disease (PD). A PD effector is alpha-synuclein (SNCA) hypothesized to selectively interact with beta glucocerebrosidase under lysosomal conditions. SNCA polymorphism rs356219 may be associated with early-age-onset PD, common among patients with GD+PD. The objective of this study was to ascertain rs356219 genotypes of GD+PD patients. All GD+PD patients at our Gaucher referral clinic were asked to participate. A GD only sex-, age-, GD genotype-, and enzyme therapy (ERT)-matched control was found for each GD+PD participant. Student's t-test was used (p-value <0.05 as significant). There were 14 GD+PD patients: all Ashkenazi Jewish; 11 males (78.6%); mean (range) age diagnosed GD 34.2 (5-62) years; 50% N370S homozygous; mild to moderate GD; 3 asplenic and only these have osteonecrosis; 5 received ERT; mean age (range) diagnosed PD was 57.8 (43-70) years; first PD sign was tremor in 9 (64.3%); cognitive dysfunction in all. In GD+PD, frequency for AG+GG (9) was greater than AA (5); in GD only, there was equality (7). Odds Ratio risk for PD increases with number minor alleles: but not significantly greater among GD+PD than GD only; in aggregate, there was no difference between cohorts for frequency of minor alleles. The limitation of this study is few GD+PD, albeit virtually all the GD+PD cohort >500 adult GD patients in our clinic. Nonetheless, as a foray into potential genetic GD susceptibility for a synucleinopathy, this study suggests the need for collaboration to achieve larger sample size. PMID- 25111980 TI - Feto-maternal allo-immunity, regulatory T cells and predisposition to auto immunity. Does it all start in utero? AB - During gestation, maternal cells traffic to the fetus leading to the natural phenomenon of microchimerism. Although their persistence in offspring has been associated with several autoimmune disorders, the precise role of maternal cells in these disorders remains unclear. We aimed to evaluate whether alloreactive maternal T cells could directly trigger a graft-vs.-host like reaction or indirectly influence the development of the offspring's regulatory T cells (Treg) favoring autoimmunity. In a specific breeding strategy, we recently reported that maternal allogeneic T cells changed fetal Treg development and their quantities in mesenteric lymph nodes, leading to early signs of inflammation in the gut later in life. Although maternal microchimeric T cells were found in newborn tissues, we could not detect any cells in the gut from adult offspring where the inflammation occurred. Thus, strongly alloreactive maternal microchimeric T cells may indirectly drive the offspring to gut inflammation. We believe these results suggest a new mechanism for predisposition to auto-immunity. PMID- 25111981 TI - Diagnostic usefulness of quantitative tissue velocity imaging and anatomic M-mode echocardiography for coronary artery diseases: A pilot study. AB - BACKGROUND AND OBJECTIVE: To explore the potential clinical usefulness and determine optimal diagnostic criteria of quantitative tissue velocity imaging and anatomic M-mode echocardiography in patients with coronary artery disease (CAD). METHODS: We used quantitative tissue velocity imaging for the measurement of systolic myocardial velocity, and anatomic M-mode echocardiography for the measurement of ventricular wall-thickening fraction in 44 subjects with suspected CAD. Subjects were classified as patients if coronary angiography demonstrated a stenosis >= 50%, and as controls if it was strictly normal. The diagnostic criteria, sensitivity, and specificity were assessed by receiver-operator curves. RESULTS: Controls had greater mean systolic myocardial velocity and ventricular wall-thickening fraction in the basal (6.59 +/- 1.25 cm/s and 0.44 +/- 0.05) and mid segment (5.23 +/- 0.93 cm/s and 0.43 +/- 0.04) than patients (5.02 +/- 1.17 cm/s and 0.29 +/- 0.04, 3.27 +/- 1.29 cm/s and 0.29 +/- 0.04, respectively, p < 0.001). Mid-segment ventricular wall-thickening fraction offered 95% sensitivity (95% CI 88.7% to 98.4%), and 98.3% specificity (95% CI 90.9% to 1.0) with an optimal cut-off point of 0.349, yielding better results than systolic myocardial velocity, which provided 83% sensitivity (95% CI 74.2% to 89.8%), 90% specificity (95% CI 79.5% to 96.2%), and optimal cut-off point 4.47. The combination of systolic myocardial velocity and ventricular wall-thickening fraction offered 97% sensitivity (95% CI 91.5% to 99.4%) CONCLUSIONS: Mid-segment ventricular wall thickening fraction might be suitable for the evaluation of patients with CAD. PMID- 25111982 TI - Coronary artery disease and 10-year outcome after hospital admission for heart failure with preserved and with reduced ejection fraction. AB - AIMS: The prognostic impact of coronary artery disease (CAD) in heart failure is debated. Whereas causes of death have been well described in patients with cardiomyopathy, little is known about how CAD influences causes of death in heart failure with preserved ejection fraction (HFPEF). We undertook a 10-year study and analysed causes of death in relation with CAD in HFPEF and in heart failure with reduced ejection fraction (HFREF). METHODS AND RESULTS: Our prospective analysis included 591 consecutive patients (320 HFPEF and 271 HFREF) hospitalized for the first time for heart failure during 2000 and followed for 10 years. History of CAD was documented in 25% of HFPEF and 39% of HFREF patients (P < 0.001). Overall, CAD was independently predictive of all-cause and cardiovascular death. CAD had powerful prognostic impact in HFREF [adjusted hazard ratio (HR) 1.60 (1.19-2.15) for all-cause death, and adjusted HR 2.01 (1.38-2.92) for cardiovascular death]. In HFPEF, the association between CAD and cardiovascular death was no longer observed after adjustment [adjusted HR 1.01 (0.69-1.50)]. In HFREF, CAD was associated with increased risk of heart failure-related (adjusted HR 2.03 (1.21-3.43)] and myocardial infarction-related fatal events [adjusted HR 3.84 (1.16-12.7)], while HFPEF patients with CAD appeared at greater risk of sudden death [adjusted HR 2.22 (1.05-4.95)]. CONCLUSION: The prognostic impact of CAD is different in HFPEF compared with HFREF. Patients with HFPEF and CAD are at high risk of cardiovascular death, especially sudden death. PMID- 25111983 TI - Cancer germline gene activation: friend or foe? PMID- 25111985 TI - Retracted manuscript: Barre B, et al. Cell Cycle 2010; 9:4795-804. PMID- 25111986 TI - Special issue "Organ replacement approaches". PMID- 25111988 TI - Tips for finding reliable health information online. PMID- 25111987 TI - Assessment of factors affecting the difficulty of caudal epidural injections in adults using ultrasound. AB - BACKGROUND: In unaided caudal epidural block (CEB), incorrect needle insertion has been reported to occur in 15% to 38% of attempts. OBJECTIVE: To statistically analyze the anatomical variables affecting difficult CEB using ultrasonographic measurement. METHODS: Preprocedural ultrasonography was performed and the following measurements were obtained in 146 patients: the distance from the skin to the apex of the sacral hiatus; the depth of the sacral canal at the apex of the sacral hiatus; the length of the sacrococcygeal ligament between the apex of the sacral hiatus and sacral base; the distance from the skin to the apex of the sacral cornu; and the distance between the apexes of bilateral cornua. One clinician, unaware of the ultrasonographic findings, performed the injections using the landmark technique. The procedures were videotaped and were subsequently reviewed by an independent investigator. RESULTS: The means (+/- SDs) of the abovementioned measurements were 12.1+/-3.7 mm, 6.1+/-2.1 mm, 25.9+/ 7.4 mm, 10.0+/-4.0 mm and 16.4+/-3.2 mm, respectively. Injections failed in 16 (11%) patients and were defined as difficult in 21 (14.4%) patients. The depth of the sacral canal at the apex of sacral hiatus (P<0.001) and the length of the sacrococcygeal ligament between the apex of the sacral hiatus and sacral base (P=0.001) were significant predictors of difficult CEB. Of all patients, 85.7% and 75.2% were correctly classified as difficult or not difficult, respectively. The cutoff values of the depth of the sacral canal at the apex of the sacral hiatus and the length of the sacrococcygeal ligament between the apex of the sacral hiatus and the sacral base to predict a difficult CEB were 3.7 mm and 17.6 mm, respectively. CONCLUSIONS: Both the depth of the sacral canal at the apex of the sacral hiatus and the length of the sacrococcygeal ligament between the apex of the sacral hiatus and sacral base are significant variables affecting the difficulty of the CEB. PMID- 25111990 TI - NIH-funded study finding: investigational oral regimen for hepatitis C shows promise. PMID- 25111989 TI - Obesity programs for children may help lower blood pressure. PMID- 25111991 TI - The NIH urges older Americans to protect their kidneys. PMID- 25111992 TI - Nurse staffing and education linked to reduced patient mortality. PMID- 25111994 TI - Abstracts of the 16th International Conference for Philosophy, Psychiatry and Psychology, June 26-29, 2014, Bulgaria. PMID- 25111993 TI - NIH-funded study finding: data supports benefits of colon cancer screening. PMID- 25111995 TI - Radio-guided parathyroidectomy for secondary hyperparathyroidism. AB - BACKGROUND: The value of gamma probes in the surgical treatment of secondary hyperparathyroidism (sHPT) was determined. METHOD: We retrospectively analyzed the clinical data of 48 sHPT patients between May 2007 and September 2011. Preoperative (99)Tc(m)- methoxyisobutyl isonitrile (MIBI) scintigraphy and high frequency ultrasonography were used for parathyroid localization. Thirty-five patients (group I) underwent conventional neck exploration and open parathyroidectomy. Thirteen patients (group II) underwent gamma probe-guided total parathyroidectomy and parathyroid transplantation. The two groups were compared in terms of the number of parathyroid resections, operative time, and postoperative changes in the blood levels of parathyroid hormone (PTH), calcium, and phosphate. RESULTS: The clinical manifestations, PTH and calcium levels, age distribution, and clinical characteristics did not differ between the two groups. The accuracy of preoperative (99)Tc(m)-MIBI scintigraphy (89.74%) for the diagnosis of hyperparathyroidism did not differ from that of ultrasonography (81.25%). However, the accuracy of (99)Tc(m)-MIBI scintigraphy (66.67%) for localizing hyperfunctioning parathyroids was significantly lower than that of ultrasonography (76.86%). The operation time was significantly longer in group I (120+/-25) min than in group II (90+/-30) min. The accuracy of parathyroid specimens were obtained in group I (2.5+/-0.5) than in group II (3.5+/-0.5). Compared with group I, group II showed a significant increase (15.4%) in the number of parathyroid resections. The PTH, calcium, and phosphate levels significantly decreased postoperatively in all patients. CONCLUSION: Intraoperative gamma probe examination confirmed that the excised specimen was parathyroid tissue and improved the accuracy of parathyroid resection. The parathyroidectomy rate was increased by 15.4% due to the use of these probes. However, the probes did not detect all ectopic parathyroids, and further research is required to clarify the underlying reasons. PMID- 25111996 TI - When you need medical care, stat. PMID- 25111998 TI - Fix mistakes on your medical bill. PMID- 25111999 TI - How to pick a medical alert system. PMID- 25111997 TI - Where should you go for heart surgery? Our new ratings of more than 400 hospitals can help you find the right one. PMID- 25112000 TI - Deadly pain pills: everyday, 46 people in the U.S. die from legal pain pills. Here's how to avoid being a statistic. PMID- 25112002 TI - [How do we treat an electrical storm in implantable cardioverter defibrillator (ICD) appropriate patients?]. PMID- 25112001 TI - Reanalyzing reverse payment settlements: a solution to the patentee's dilemma. PMID- 25112003 TI - [Reconstruction of full-thickness nasal alar defect with combined nasolabial flap and free auricular composite flap]. AB - OBJECTIVE: To investigate the technique and its effect of combined nasolabial flap and free auricular composite flap for full-thickness nasal alar defect. METHODS: From March 2010 to March 2013, 9 patients with full-thickness nasal alar defects were treated with combined nasolabial flaps and free auricular composite flaps. Composite auricular flap was used as inner lining and cartilage framework. The nasolabial flap at the same side was used as outer lining. RESULTS: All the patients were followed up for 6-18 months (average, 12 months). All the 9 composite auricular flaps survived completely. Epidermal necrosis happened at the distal end of 1 nasolabial flap. Alar rim was almost normal and symmetric nose was achieved in 6 cases. The arc and the thickness of the alar rim was not enough in 3 cases, resulting in asymmetric appearance. CONCLUSIONS: The survival area of auricular composite flap can be enlarged with nasolabial flap. The auricular helix edge can be reserved to reconstruct nasal alar rim with smooth and natural arc. Large full-thickness nasal alar defedts can be reconstructed with combined nasolabial flaps and free auricular composite flaps. PMID- 25112004 TI - [Comparative study in reconstruction of tongue defect with thin anterolateral flap and forearm flap]. AB - OBJECTIVE: To compare the thin anterolateral flap with forearm flap in tongue defect repairing, and to introduce our methods and experiences in the tongue reconstruction with the thin anterolateral flap. METHODS: The clinicopathologic data of 46 cases with tongue carcinoma were obtained from School of Stomatology, Nanjing University Medical Center, Nanjing University from December 2009 to December 2011. To compare two methods of incidence of vascular crisis, tongue shape, language and swallowing functional recovery. RESULTS: 46 patients with tongue carcinoma were performed the tongue reconstruction in 12 month, which 12 cases were used the thin anterolateral flap and 34 cases were used the forearm flap. In the thin anterolateral flap group, All cases were succeeded. 1 case occurs vascular crisis. In the forearm flap group, 33 cases were succeeded, and 1 case occurs necrosis. 3 cases occurs vascular crisis. The results of comparing two methods showed that: no obvious differences in the tongue shape, and no obvious differences in the function of language and swallowing. CONCLUSIONS: There no obvious differences in the reconstruction of tongue defect between the thin anterolateral flap and the forearm flap. The thin anterolateral flap have some advantages: little influence is on the donor site, the flap extent is abundant, the donor site is not spectacular. The thin anterolateral flap should be piror method for the tongue defect repairing. PMID- 25112005 TI - [Application of the expanded distant skin flaps for the facial and cervical deformities]. AB - OBJECTIVE: To investigate the application of expanded distant skin flaps for the facial and cervical deformities. METHODS: 96 patients with facial and cervical deformities who underwent reconstructive surgery with expanded distant skin flaps were retrospectively reviewed and followed up. RESULTS: Good results were achieved in 95 cases. Necrosis happened in the distal end of one flap. The patients were followed up for 1-8 years with good cosmetic results, such as well matched flap texture and color. CONCLUSION: The expanded distant skin flap is suitable and reliable for facial and cervical deformities. PMID- 25112006 TI - [Primary report of single rib-cartilage recombination transplantation in Binder syndrome treatment]. AB - OBJECTIVE: To explore the surgical methods and advantages of single rib-cartilage recombination transplantation in Binder syndrome treatment. METHODS: Five patients were treated with single rib-cartilage recombination transplantation. We harvested only the seventh costal cartilage including partial costal bone of the same rib to correct all the deformities. The rib was divided into 3 parts: 1 I shaped cartilage, 1 inverted-T-shaped cartilage, and 1 C-shaped implant (later divided into a C and a reversed-C implant) composed of rib bone and cartilage. The first 2 parts were constructed to an L-shaped implant for nasal dorsum augmentation, collumella support, and nasal base elevation. The C-shaped and reversed-C-shaped implants were placed on both sides of the pyriform aperture. RESULTS: All patients were followed up for eighteen to thirty months. No apparent deviation on the nasal support was found. CONCLUSION: Single rib-cartilage recombination transplantation in Binder syndrome treatment has lots of advantages, such as less morbidity, rapid recovery, and good results. PMID- 25112007 TI - [Correction of minor breast ptosis by subfascia breast augmentation with periareolar incision and anatomic mammary implant]. AB - OBJECTIVE: To correct the minor breast ptosis with minimal breast scar. METHODS: 32 cases with minor breast ptosis were corrected by subfascia breast augmentation with periareolar incision and anatomic mammary implant. RESULT: Breast ptosis was completely or mostly corrected in all the patitents with periareola scar, avoiding the vertical breast scar. Except for short-time effusion in 2 cases, no other complication happened. CONCLUSIONS: Subfascia breast augmentation with periareolar incision and anatomic mammary implant can effectively correct minor breast ptosis with minimal breast scar and less complication. PMID- 25112008 TI - [Comparative study of three different methods for penile reconstruction]. AB - OBJECTIVE: To compare the effect of three methods for penile reconstruction. METHODS: From Sept. 2000 to Dec. 2012, penile reconstruction was performed in 48 cases with free scapular flap transplantation, or pedicled superficial circumflex iliac artery skin flap, or anterolateral thigh skin flap pedicled with lateral circumflex femoral artery. The flaps were 12.0-14.5 cm in length, 10-12 cm in width and the urethra perimeter was about 2-3 cm. RESULTS: Free scapular flaps were used in 21 cases, with flap failure in 3 cases due to insufficient blood supply. Malleable penile prosthesis was implanted in 11 cases, which was exposed in 3 cases. Groin skin flaps were used in 21 cases, with flap failure in 8 cases due to insufficient blood supply. Malleable penile prostheses were implanted in 7 cases, which was exposed in 3 cases. Anterolateral thigh skin flaps were used in 6 cases, with flap failure in 2 cases due to necrosis and infection. No prosthesis was implanted in this group. All the failure cases underwent secondary reconstruction with successful results. 37 cases were followed up for 1-6 years, avevage 2.5 years. 26 cases were satisfied with the results of appearance and function. CONCLUSIONS: Among these three methods, the free scapular flap is most recommended for its high survival rate, low complication rate and high patient satisfaction. PMID- 25112009 TI - [Efficacy of dexmedetomidine combined with remifentanil for lower eyelid blepharoplasty]. AB - OBJECTIVE: To explore the feasibility and safety of dexmedetomidine combined with remifentanil for lower eyelid blepharoplasty. METHODS: 50 patients undergoing lower eyelid blepharoplasty ASA I - II were randomly divided into 2 groups (25 in each group) as observation group and control group. Dexmedetomidine (0.3 microg x kg(-1) x h(-1)) and remifentanil (0.05 microg x kg(-1) x min(-1)) were used in observation group. Local anesthesia by lidocaine (1%) combined with midazolam (0.04 mg/kg) intravenous sedation were used in control group. HR, mean arterial pressure (MAP), heart rate (HR), breathing rate (RR), pulse oxygen saturation (SpO2) change were monitored and recorded before and after the administration of the drug, as well as at the beginning of operation, during the operation, at the end of the operation, and 5 minutes after the operation. Patients sedation degree was evaluated by Ramsay. Operation time, recovery time, the incidence of adverse reactions, the satisfaction of patients and doctors were also recorded. RESULTS: Patients had no obvious difference of intraoperative MAP, RR, SpO2, operation time and postoperative recovery time between the two groups (P > 0.05). Compared with control group, HR during the operation were decreased significantly [(64.2 +/- 8.2) bpm, P < 0.05] in observation group. In control group, there were 18 cases of patients with agitation, but they endured the operation anyway. In observation group, 24 cases of patients underwent operation without agitation. The satisfaction of patients and the operation doctors (96%) in observation group were markedly higher than that in control group (P < 0.05). CONCLUSION: Dexmedetomidine combined with remifentanil is practical and safe. The effect of reducing HR should be noticed. PMID- 25112010 TI - [Effect of postoperative analgesia with dexmedetomidine on the survival rate of amputated finger replantation]. AB - OBJECTIVE: To observe the effect of postoperative analgesia with dexmedetomidine on the survival rate of amputated finger replantation. METHODS: 91 cases, who was going to receive amputated finger replantation, were randomly divided into group A (n = 48) and B (n = 43). PCIA (patient-controlled intravenous analgesia) was set immediately after operation in group A (fentanyl 1.0 mg + tropisetron 4.0 mg + 10 mg + dexmedetomidine 200 microg + saline 100 ml) and group B (same as group A except dexmedetomidine). Background infusion is 2 ml/h with a bolous of 0.5 ml and lockout time is 15 min. postoperative VAS score, Ramsay score, condition of replanted fingers and other adverse events at the 0-6 h, 6-12 h, 12-24 h and 24 48 h were recorded and analyzed. RESULTS: The age, sex, height, weight, amputated time (Ts), revascularized time (Tt) in the two groups were not statistically different (P > 0.05). Postoperative VAS score in the two groups was significantly different at the 0-6 h, 6-12 h, 12-24 h and 24-48 h (P < 0.05), but Ramsay score was not (P > 0.05). The highest and lowest postoperative VAS score and Ramsay score were markedly different between two groups (P < 0.05). 3 of the 60 fingers in group A experienced vascular crisis and 2 underwent vascular explore surgery. 13 of 56 fingers in group B occurred vascular crisis, and 10 underwent vascular explore surgery, showing significant difference between the two groups (P < 0.05). PCIA adverse reactions showed no difference between the two groups (P > 0.05). Bradycardia and hypotension didn't happen in any patients in the two groups. 4 weeks after surgery, the survival rate was 96.7% (58/60) in group A, and 83.9% (47/56) in group B (P < 0.05). CONCLUSION: Postoperative analgesia with dexmedetomidine as an adjuvant can increase the survival rate of replantation fingers with high safety. PMID- 25112011 TI - [Functions of retinoic acid on the biological characteristics of human embryonic stem cells]. AB - OBJECTIVE: To analyze the influence of retinoic acid (RA) on the undifferentiated state and EB formation abilities of human embryonic stem cells. METHODS: The biological characteristics of H9 ESCs after RA treatment were characterized by real-time PCR, MTS proliferation assay and immunofluorescence staining. The expression of three germ layers markers, osteogenic differentiation markers and adipogenic differentiation markers in H9-differentiated embryoid bodies (EBs) with RA treatment were quantified by real time PCR. RESULTS: The proliferation of H9 ESCs in the early logarithmic growth phase was accelerated by RA treatment. In addition, RA induced differentiation of H9 ESC coupled with morphology changes, decreased expression of undifferentiated markers Oct4, Nanog, Sox2 and OCT4 mRNA binding protein Lin28 at mRNA level, and reduced expression of Oct4 at protein level. RA induced formation of cavities in EBs. Real time PCR results showed that the expressions of ectodermal markers: NeuroD1, Noggin; mesodermal markers: Brachyury, Twist and endodermal markers: AFP, GATA-4 were significantly increased (P < 0.05), especially for AFP (P < 0.01), by RA treatment in a dose-dependent manner. In addition, the expression of adipogenic differentiation marker C/EBPalpha was increased while the osteogenic differentiation marker OPN was decreased in EBs after RA treatment for 5 days. CONCLUSIONS: High concentrations of RA induced the loss of stemness in H9 ESCs and excessive differentiation in EBs, and damaged the balance between osteogenic and adipogenic differentiation during early EB differentiation, which may be relevant to the congenital malformations. PMID- 25112012 TI - [The expressions of notch genes in human keloid-derived mesenchymal-like stem cells]. AB - OBJECTIVE: To study the expressions of Notch1-4 gene in human keloid-derived mesenchymal-like stem cells, and to explore the Notch signaling pathway's role in the formation of keloid. METHODS: Keloid samples were collected to harvest human keloid-derived mesenchymal-like stem cells through two-step enzymatic dissociation method. By flow cytometry, cell phenotype of primary and P3 generation were analyzed. By immunocytochemistry, the expressions of Oct4, vimentin and CK19 were examined. Keloid-derived mesenchymal-like stem cells were induced into osteoblasts in vitro and calcium deposition was detected by Alizarin red S stain. Realtime polymerase chain reaction (RT-PCR) was used to detect the expressions of Notch1-4 mRNA in keloid-derived mesenchymal-like stem cells. RESULTS: Flow cytometry showed that keloid-derived mesenchymal-like stem cells of primary and P3 generation highly expressed CD29, CD44, CD90 from the typical MSC phenotype marker, but they failed to express HSC phenotype markers, such as CD34 and CD45. The results of immunocytochemistry showed that Oct4 from pluripotent stem cell markers and vimentin from mesenchymal cell markers was positive and CK19 from epithelial cell markers was negative. After induced differentiation into osteoblasts in vitro after 21 day, calcium nodules could be seen clearly; Notch1-4 gene were expressed in keloid-derived mesenchymal-like stem cells through RT-PCR. The relative quantitative of Notch2, Notch3 gene were higher than Notch1, Notch4 gene (P < 0.05). CONCLUSIONS: The expression difference of different subtypes from Notch gene in human keloid-derived mesenchymal-like stem ceils may be related to self-renewal, proliferation, differentiation, and participate in the formation of keloid. PMID- 25112013 TI - [Preliminary study of the biological characteristics of fibroblasts in human granulation tissue in vitro]. AB - OBJECTIVE: To explore the biological characteristics of fibroblasts in adult granulation tissue in vitro, including cell viability, CD phenotypic, factor and protein expression, and differentiation, so as to facilitate further research of the role of fibroblasts in early wound healing. METHODS: Fibroblasts were isolated from human granulation tissue and cultured by mechanical and enzymatic digestion method. The cell morphology and proliferation were observed under inverted phase contrast microscope. The first and third passages of cells' growth curve were drawn respectively. The surface markers (CD105, CD73, CD90, CD44, CD34, CD45, CD19, CD11b, HLA-DR) of the first and third passage fibroblasts were identified by Flow Cytometry. And the expression of Vimentin, CK19, CD31 and Factor VIII were detected by immunocytochemistry. RESULTS: Primary cultured fibroblasts were short spindle, polygonal and irregular in shape. The morphology of fibroblasts were uniform by repeatedly passage cultured in vitro and showed spindle-shaped. The proliferative capacity of the fibroblasts were not significantly different, with logarithmic growth phase. From 1 to 4 days, The primary and third passage cells' proliferation was no difference (P > 0.05), After the five days, the proliferative ability of third generation was better than the primary passage (P < 0.01). All fibroblasts highly expressed mesenchymal stem cells' surface markers CD105, CD73, CD90 and CD44, and didnt express hematopoietic stem cells' surface markers CD34, CD45, CD19, CD11b and HLA-DR. The expression of mesenchymal stem cells' surface markers in third generation of cells were increased significantly. Immunocytochemistry showed positive expression of Vimentin, CD31, and negative expression of CK19 and Factor VIII. CONCLUSIONS: Fibroblasts in human granulation tissue show the biology characteristics of Mesenchymal Stem Cells. Some biological markers of endothelial cells are expressed in fibroblasts in granulation tissue. The fibroblasts may play an important role during the process of endothelial to mesenchymal transformation in early wound healing. PMID- 25112014 TI - [In vitro induction of human breast adipose-derived stem cells into epithelial like cells by co-culturing]. AB - OBJECTIVE: To explore the feasibility of the transdiferentiation of human breast adipose-derived stem cells (hbASCs) into mammary epithelial-like cells after co culturing in Transwell in vitro. METHODS: The third passage hbASC and the HBL-100 cell line were co-cultured in a Transwell culture system for 15 days. The hbASCs were observed and identified by inverted phase contrast microscope and transmission electron microscopy, and immunocytochemistry staining in the induced and control groups. RESULTS: Both the third passage hbASCs and the HBL-100 cell line cells could adhere and grow rapidly after co-culture in the Transwell system. After co-culture for 15 days, the morphology of some induced hbASCs changed into epithelial-like cells. Some induced hbASCs showed positive expression of CK18, CK19 by immunocytochemistry staining, and typical epithelium cells with microvilli, desmosomes and tonofilaments observed under TEM. The positive rate of CK18 and CK19 was (24.4 +/- 12.0)% and (21.6 +/- 16.4)% in experimental group, and (1.8 +/- 1.7)% and (1.1 +/- 0.6)% in control group. CONCLUSION: The data suggests that hbASCs may have the potential to transdifferentiate into human mammary epithelial-like cells after co-culturing in Transwell in vitro. PMID- 25112016 TI - Responding to the peer review. PMID- 25112015 TI - [Vascular supply of intrinsic muscles of foot and anatomic basis for muscular flaps design]. AB - OBJECTIVE: To investigate the vascular supply of intrinsic muscles of foot and anatomic basis for muscular flap design. METHODS: A radiopaque injectate (lead oxide-gelatin mixtures, 26 ml/kg) was injected into 10 fresh cadavers. The dissected regions were photographed and each intrinsic muscles on the foot was removed and radiographed. The number, type, diameter of vascular branches of muscles and their distributions were observed. The area of the vascular territory supplied by each source vessel was calculated using Scion Image for Windows software. RESULTS: There were significant architectural differences among the intrinsic muscles. The muscles length varied from 22.5mm to 116.2mm [average, (66.1 +/- 23.2)mm]. The measured fiber length were relatively consistent, ranging from 14.2 mm to 27.5 mm [average, (20.2 +/- 4.5)mm]. There are 63 vascular branches into the 23 foot muscles, each muscle having average branches of 3.2 +/- 0.8. The average diameter of branches, the length and width of each vascular territorial area is (0.8 +/- 0.3) mm, (2.2 +/- 0.8) cm, and (0.9 +/- 0.4) cm, respectively. Other findings included that some muscles were not present in some cadavers. CONCLUSIONS: The blood supply of intrinsic muscles of foot is abundant with different diameter and distributions of branches. There is an anatomic basis for muscular or musculoosseous flap design. There are 7 intrinsic muscles with large and reliable vascular supply which can be chosen as muscular flaps. PMID- 25112017 TI - Preparing quality improvement, research, and evidence-based practice manuscripts. PMID- 25112018 TI - Evaluation of the effect of cranberry juice on symptoms associated with a urinary tract infection. AB - The purpose of this research was to correlate daily consumption of cranberry juice and symptoms of a diagnosed UTI among 26 volunteer adult female patients. PMID- 25112019 TI - The effect of collection method on urinalysis results in women with pelvic organ prolapse. AB - Midstream clean catch and catheterized urine specimens were obtained for each patient and samples were compared by microscopic urinalysis. The results of this study demonstrate that a midstream clean catch does not yield accurate urinalysis results in women with advanced urogenital prolapse. PMID- 25112020 TI - Adding to the evidence base: the effect of collection method on urinalysis in women with pelvic organ prolapse. PMID- 25112021 TI - A nurse practitioner's experience in a post-graduate nurse practitioner urology fellowship. AB - In 2012 the Division of Urologic Surgery at Washington University School of Medicine developed and piloted a 12-month post-graduate nurse practitioner fellowship. The author completed this fellowship. This is a report on the experiences. PMID- 25112022 TI - Monolateral purple urine bag syndrome in a patient with bilateral nephrostomy tubes. AB - Purple urine bag syndrome (PUBS) is a constellation of findings resulting in purple discoloration of the urine and/or urine drainage bag(s) occurring in patients with long-term urinary indwelling catheters. Other causative factors may include constipation, female gender, the presence of bacteria containing sulphatase and phosphatase enzymes, and alkaline urine. While the contributing factors for PUBS are linked with high morbidity, PUBS itself is a benign condition. A case study of monolateral PUBS in a patient with bilateral nephrostomy tubes (NTs) is presented. PMID- 25112023 TI - Conservative management of acute scrotal edema. AB - Scrotal edema is a prevalent issue. It is difficult to treat and has a myriad of causes. Historical treatments for scrotal edema have lacked efficacy. If treated before fibrosis occurs, surgery can be avoided. A method for conservative management is outlined. PMID- 25112024 TI - Female stress urinary incontinence: an evidence-based, case study approach. AB - Over half of all women are affected by urinary incontinence at some point during their lives. Due to patients' embarrassment and health care providers' reluctance to discuss this sensitive subject, many women may go untreated, and in turn, suffer with disruptive symptoms and co-morbid complications associated with urinary incontinence. This article highlights a literature review of the evaluation and management of female stress urinary incontinence using a corresponding case study example. Increasing awareness and implementing evidence based, nonsurgical treatment options are essential components of high-quality care for women with stress urinary incontinence. Urologic nurses and other health care professionals are in an ideal position to evaluate and identify strategies for the treatment of female stress urinary incontinence. PMID- 25112025 TI - Electrocoagulation treatment of metal finishing wastewater. AB - Electrocoagulation has been found to be a consistent and reliable industrial wastewater treatment process capable of removing heavy metals to levels well below pretreatment discharge standards. Results from the testing of a 113 L/min pilot scale electrocoagulation unit indicated that electrocoagulation was capable of decreasing the cadmium, chromium, and nickel concentrations from 0.14, 18.1, and 0.06 parts per million (ppm) to 0.029, 0.039, and 0.020 ppm respectively, at a 1-min hydraulic retention time. In the presence of a strong chelating substance, electrocoagulation performance was found to be effective in reducing both chromium and nickel concentrations to levels well below discharge limits. At a pH of 8.0, chromium and nickel influent concentrations of 0.328 and 0.062 ppm, respectively, were reduced to 0.005 and 0.04 ppm. The electrocoagulation removal efficiency for chromium remained high at over 98% and appeared to be unaffected by the presence of chelating substances. Utilizing aluminum as the sacrificial anode improved the removal efficiency of targeted heavy metals when the industrial wastewater was treated under acidic conditions. At a pH of 5.6, the influent concentrations of the regulated heavy metals cadmium, chromium, and nickel were reduced from 0.55, 49.7, and 13.7 ppm, respectively, to 0.013, 2.7, and 0.8 ppm at a 1-min hydraulic retention time. The results of these tests suggest that the formation of ferric hydroxide and aluminum hydroxide through the electrocoagulation process may be an effective approach for treating metal finishing wastewaters. PMID- 25112026 TI - Monitoring and remediation of organochlorine residues in water. AB - This study monitored the presence of organochlorines in drinking water in Kafr-El Sheikh, Ebshan, Elhamoul, Mehalt Aboali, Fowa, Balteem, and Metobess in the Kafr El-Sheikh Governorate, Egypt, to evaluate the efficiencies of different remediation techniques (advanced oxidation processes [AOPs] and bioremediation) for removing the most frequently detected compound (i.e., lindane) in drinking water. The results showed the presence of several organochlorine residues at all water sampling sites. Lindane was detected with high frequency relative to other detected organochlorines in water. Nano photo-Fenton-like reagent was the most effective treatment for lindane removal in drinking water. Bioremediation of lindane by effective microorganisms removed 100% of the initial concentration of lindane after 23 days of treatment. The study found that there is no remaining toxicity of lindane-contaminated water after remediation on treated rats relative to the control with respect to histopathological changes in the liver and kidneys. Therefore, AOPs, particularly those with nanomaterials and bioremediation, can be regarded as safe and effective remediation technologies for lindane in water. PMID- 25112027 TI - Efficient control of odors and VOC emissions via activated carbon technology. AB - This research study was undertaken to enhance the efficiency and economy of carbon scrubbers in controlling odors and volatile organic compounds (VOCs) at the wastewater collection and treatment facilities of the Bureau of Sanitation, City of Los Angeles. The butane activity and hydrogen sulfide breakthrough capacity of activated carbon were assessed. Air streams were measured for odorous gases and VOCs and removal efficiency (RE) determined. Carbon towers showed average to excellent removal of odorous compounds, VOCs, and siloxanes; whereas, wet scrubbers demonstrated good removal of odorous compounds but low to negative removal of VOCs. It was observed that the relative humidity and empty bed contact time are one of the most important operating parameters of carbon towers impacting the pollutant RE. Regular monitoring of activated carbon and VOCs has resulted in useful information on carbon change-out frequency, packing recommendations, and means to improve performance of carbon towers. PMID- 25112028 TI - Partial nitrification in sequencing batch reactors treating low ammonia strength synthetic wastewater. AB - Sequencing batch reactors fed with low ammonium strength synthetic wastewater under C/N ratios of 0.5, 1.5, and 3.0 were used to investigate the transition from full to partial nitrification. Two strategies for establishing partial nitrification, aeration duration control and process parameter control, were compared. The effect of C/N ratio on nitrite accumulation was also evaluated. Results showed that partial nitrification established by controlling aeration duration presented better performance with higher nitrite accumulation. An increase of C/N ratio helped nitrite accumulation; however, non-filamentous bulking of sludge happened at high C/N ratio. Based on mass balances for nitrogen, results for nitrogen during full and partial nitrification were distinct from one another. For low C/N ratio, during full nitrification, almost 100% of NH(4+)-N was oxidized to NO(3-)-N without nitrogen loss; however, nitrogen loss increased obviously during partial nitrification, which indicated that dissolved oxygen concentration and C/N ratio influenced nitrogen loss significantly during nitrification. PMID- 25112029 TI - Performance evaluation of a dual-flow recharge filter for improving groundwater quality. AB - A dual-flow multimedia stormwater filter integrated with a groundwater recharge system was developed and tested for hydraulic efficiency and pollutant removal efficiency. The influent stormwater first flows horizontally through the circular layers of planted grass and biofibers. Subsequently, the flow direction changes to a vertical direction so that water moves through layers of pebbles and sand and finally gets recharged to the deep aquifers. The media in the sequence of vegetative medium:biofiber to pebble:sand were filled in nine proportions and tested for the best performing combination. Three grass species, viz., Typha (Typha angustifolia), Vetiver (Chrysopogon zizanioides), and St. Augustine grass (Stenotaphrum secundatum), were tested as the best performing vegetative medium. The adsorption behavior of Coconut (Cocos nucifera) fiber, which was filled in the middle layer, was determined by a series of column and batch studies.The dual flow filter showed an increasing trend in hydraulic efficiency with an increase in flowrate. The chemical removal efficiency of the recharge dual-flow filter was found to be very high in case of K+ (81.6%) and Na+ (77.55%). The pH normalizing efficiency and electrical conductivity reduction efficiency were also recorded as high. The average removal percentage of Ca2+ was moderate, while that of Mg2+ was very low. The filter proportions of 1:1 to 1:2 (plant:fiber to pebble:sand) showed a superior performance compared to all other proportions. Based on the estimated annual costs and returns, all the financial viability criteria (internal rate of return, net present value, and benefit-cost ratio) were found to be favorable and affordable to farmers in terms of investing in the developed filtration system. PMID- 25112030 TI - Methylmercury accumulation and toxicity to cyanobacteria: implications of extracellural polymeric substances and growth properties. AB - This investigation examines how extracellular polymeric substances (EPSs) and environmental factors influence the bioaccumulation of monomethylmercury (MMeHg) using a culture of Microcystis aeruginosa, which dominates eutrophic reservoir populations. The identified EPSs were classified as carbohydrates and proteins. Evaluation of the bioaccumulation of MMeHg in cells by multiple regression analysis reveals that the concentration of EPSs in filtrate, the initial concentration of MMeHg in media, and the age of the culture significantly affected the amount of accumulation of MMeHg. Based on the composition profiles, the concentrations of soluble carbohydrates were significantly higher in the cells with bioaccumulated MMeHg than in the control ones. Preliminary results based on SEM-map investigations suggest that most of the MMeHg accumulated in the cytoplasm (intracellular). Additionally, the effective concentrations (EC50) of MMeHg that inhibit the growth of M. aeruginosa were 5.1 to 7.8 microg/L in the logarithmic phase and 2.5 to 4.6 microg/L in the stationary phase. PMID- 25112032 TI - Hydrogen production and wastewater treatment in a microbial electrolysis cell with a biocathode. AB - The broad application of microbial electrolysis cells (MECs) requires a system characterized by low cost and high operational sustainability. Biocathode MECs, which only require bacteria as the cathode catalysts, can satisfy these demands and have attracted considerable attention in recent years. In this study, we have examined biocathode alternatives to the typical platinum cathode in a single chamber, membrane-free MEC. This biocathode MEC has been used for simultaneous hydrogen production and wastewater treatment. The results showed that hydrogen production rates increased in response to an increase in voltage. At an applied voltage of 0.9 V, the biocathode MEC achieved a hydrogen production rate of 0.39 m3 m(-3) d(-1), with a current density of 134 Am(-3), chemical oxygen demand (COD) removal of 90%, a coulombic efficiency of 63%, a cathodic hydrogen recovery of 37%, and an energy efficiency based on an electricity input of 67%. The biocathode demonstrated sufficient electrocatalytic activity and achieved a performance level comparable to that of the platinum cathode. Moreover, the substrate that was used to simulate wastewater in this study was efficiently treated by the MEC. PMID- 25112031 TI - Hydraulic and hydrogeochemical characteristics of a riverbank filtration site in rural India. AB - A riverbank filtration (RBF) system was tested along the Kali River in rural part of the state of Karnataka in India. The polluted river and water from open wells served the local population as their principal irrigation water resource and some used it for drinking. Four RBF wells (up to 25 m deep) were installed. The mean hydraulic conductivity of the well field is 6.3 x 10(-3) cm/s and, based on Darcy's law, the water travel time from the river to the principal RBF well (MW3) is 45.2 days. A mixing model based on dissolved silica concentrations indicated that, depending on the distance from the river and closeness to irrigated rice fields, approximately 27 to 73% of the well water originated from groundwater. Stable isotopic data indicates that a fraction of the water was drawn in from the nearby rice fields that were irrigated with river water. Relative to preexisting drinking water sources (Kali River and an open well), RBF well water showed lower concentration of dissolved metals (60.1% zinc, 27.8% cadmium, 83.9% lead, 75.5% copper, 100% chromium). This study demonstrates that RBF technology can produce high-quality water from low-quality surface water sources in a rural, tropical setting typical for many emerging economies. Further, in parts of the world where flood irrigation is common, RBF well water may draw in infiltrated irrigation water, which possibly alters its geochemical composition. A combination of more than one mixing model, silica together with stable isotopes, was shown to be useful explaining the origin of the RBF water at this study site. PMID- 25112033 TI - Formation kinetics of gemfibrozil chlorination reaction products: analysis and application. AB - Aqueous chlorination kinetics of the lipid regulator gemfibrozil and the formation of reaction products were investigated in deionized water over the pH range 3 to 9, and in two wastewater matrices. Chlorine oxidation of gemfibrozil was found to be highly dependent on pH. No statistically significant degradation of gemfibrozil was observed at pH values greater than 7. Gemfibrozil oxidation between pH 4 and 7 was best represented by first order kinetics. At pH 3, formation of three reaction products was observed. 4'-C1Gem was the only reaction product formed from pH 4-7 and was modeled with zero order kinetics. Chlorine oxidation of gemfibrozil in two wastewater matrices followed second order kinetics. 4'-C1Gem was only formed in wastewater with pH below 7. Deionized water rate kinetic models were applied to two wastewater effluents with gemfibrozil concentrations reported in literature in order to calculate potential mass loading rates of 4'C1Gem to the receiving water. PMID- 25112034 TI - Polyphosphate- and glycogen-accumulating organisms in one EBPR system for liquid dairy manure. AB - Two enhanced biological phosphorus removal (EBPR) sequencing batch reactors (SBR1, SBR2) treating liquid dairy manure were operated with the same hydraulic retention time (HRT) and solids retention time (SRT), but with different aeration cycles. During eight months of operation, both SBRs achieved good removal of total phosphorus (P) (TP; 56.8 and 73.5% for SBR1 and SBR2 respectively) and of orthophosphate (OP; 76.2 vs. 82.7%, P < 0.05). Growth dynamics of presumptive phosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs) were examined by quantitative polymerase chain reaction (qPCR). SBR1 was enriched with a greater abundance of PAOs while SBR2 was characterized by a greater abundance of GAOs. These results demonstrate the capability of EBPR of dairy manure and challenge conventional wisdom, since greater abundance of PAOs in EBPR system was not associated with improved OP removal and greater abundance of GAOs did not indicate deterioration of the EBPR system. PMID- 25112035 TI - Expert recognition. PMID- 25112036 TI - QNI celebrates outstanding service. PMID- 25112038 TI - State nurseries bridge the disadvantaged gap. PMID- 25112039 TI - Infant mortality rates 'lagging behind' European counterparts, new report reveals. PMID- 25112037 TI - Call for HPV vaccine reduction. PMID- 25112040 TI - New guidelines advocate better birth choice. PMID- 25112041 TI - Increase in allergy-caused hospital admissions. PMID- 25112042 TI - Almost half of asthma deaths are avoidable. PMID- 25112043 TI - Children need health education, says TV doc. PMID- 25112044 TI - Making progress on children and young people's health. PMID- 25112045 TI - Not to be sneezed at. PMID- 25112046 TI - Childhood infestations: prevention and eradication. PMID- 25112047 TI - 'Is Healthy Start working? Not by a long means'. PMID- 25112048 TI - Vitamin D--raising awareness of low intakes. PMID- 25112049 TI - All you need to know about omega-3s. PMID- 25112050 TI - Factors that influence changes in wheelchair cushion performance over time. AB - Wheelchair cushions can be used for many hours every day. Like all devices, cushions degrade over time, losing the ability to provide adequate support. Little is known about the changes that cushions undergo after typical everyday use. This project was designed to monitor cushion performance over time with the objective to identify the most important factors that predict cushion degradation. Wheelchair users and their cushions were evaluated multiple times. Information was collected about participants' posture and activities, their cushions, and use of their cushions. Cushion performance was determined by measuring interface pressure using a buttock model. Data analysis proceeded in two steps. First, principal component analysis was run to reduce the number of variables. Second, multiple regression determined which variables influenced the interface pressure performance variables. Results indicated that user characteristics and the manner in which the cushion is used have a greater influence on cushion performance than the chronological age of the cushion. This result can be useful to clinicians who should query users about cushion use when investigating the need to replace a cushion. Finally, this information is applicable to policies that govern cushion replacement and indicted that wear on a cushion is not equivocal across users. PMID- 25112052 TI - Assistive technology as a predictor of general or alternate assessment among elementary-aged students with autism spectrum disorders. AB - The No Child Left Behind Act of 2001 specifically mandates that all students participate in the general assessment process or some form of alternate assessment as a measure of school accountability for student academic progress. Although levels of communication difficulties, intellectual impairment, and specific diagnoses such as autism spectrum disorders (ASDs) are correlated with increased probability of participating in alternate assessment methods, very little empirical research has focused on identifying predictors for students' assessment modality. Archival data from the Special Education Elementary Longitudinal Study (SEELS; 2005) were used to examine variables that predict whether elementary school students with ASD participated in the general or alternate assessment. Results indicated that receptive and expressive communication abilities appear to influence participation in the general vs. alternate assessment in tandem with access to assistive technology. Students with ASDs were approximately 2.71 times more likely to participate in the general assessment when they had access to assistive technology. Next, we performed a second, follow-up analysis for only ASD students with communication problems. The odds ratio value increased to 14.9 indicating that ASD students with communication problems that had access to assistive technology were almost 15 times more likely to participate in the general assessment than students with communication problems without access to assistive technology. PMID- 25112051 TI - Analysis of electrode shift effects on wavelet features embedded in a myoelectric pattern recognition system. AB - Myoelectric pattern recognition systems can translate muscle contractions into prosthesis commands; however, the lack of long-term robustness of such systems has resulted in low acceptability. Specifically, socket misalignment may cause disturbances related to electrodes shifting from their original recording location, which affects the myoelectric signals (MES) and produce degradation of the classification performance. In this work, the impact of such disturbances on wavelet features extracted from MES was evaluated in terms of classification accuracy. Additionally, two principal component analysis frameworks were studied to reduce the wavelet feature set. MES from seven able-body subjects and one subject with congenital transradial limb loss were studied. The electrode shifts were artificially introduced by recording signals during six sessions for each subject. A small drop in classification accuracy from 93.8% (no disturbances) to 88.3% (with disturbances) indicated that wavelet features were able to adapt to the variability introduced by electrode shift disturbances. The classification performance of the reduced feature set was significantly lower than the performance of the full wavelet feature set. The results observed in this study suggest that the effect of electrode shift disturbances on the MES can potentially be mitigated by using wavelet features embedded in a pattern recognition system. PMID- 25112053 TI - A paired outcomes study comparing two pediatric wheelchairs for low-resource settings: the regency pediatric wheelchair and a similarly sized wheelchair made in Kenya. AB - This comparative study of two similar wheelchairs designed for less-resourced settings provides feedback to manufacturers, informing ongoing improvement in wheelchair design. It also provides practical familiarity to clinicians in countries where these chairs are available, in their selection of prescribed wheelchairs. In Kenya, 24 subjects completed 3 timed skills and assessments of energy cost on 2 surfaces in each of 2 wheelchairs: the Regency pediatric chair and a pediatric wheelchair manufactured by the Association of the Physically Disabled of Kenya (APDK). Both wheelchairs are designed for and distributed in less-resourced settings. The Regency chair significantly outperformed the APDK chair in one of the energy cost assessments on both surfaces and in one of three timed skills tests. PMID- 25112054 TI - Improving mouse controlling and movement for people with Parkinson's disease and involuntary tremor using adaptive path smoothing technique via B-spline. AB - Many input devices are available for interacting with computers, but the computer mouse is still the most popular device for interaction. People who suffer from involuntary tremor have difficulty using the mouse in the normal way. The target participants of this research were individuals who suffer from Parkinson's disease. Tremor in limbs makes accurate mouse movements impossible or difficult without any assistive technologies to help. This study explores a new assistive technique-adaptive path smoothing via B-spline (APSS)-to enhance mouse controlling based on user's tremor level and type. APSS uses Mean filtering and B spline to provide a smoothed mouse trajectory. Seven participants who have unwanted tremor evaluated APSS. Results show that APSS is very promising and greatly increases their control of the computer mouse. Result of user acceptance test also shows that user perceived APSS as easy to use. They also believe it to be a useful tool and intend to use it once it is available. Future studies could explore the possibility of integrating APSS with one assistive pointing technique, such as the Bubble cursor or the Sticky target technique, to provide an all in one solution for motor disabled users. PMID- 25112055 TI - Use of assistive technologies in academic libraries: a survey. AB - The present article attempts to highlight the use of assistive technologies in academic libraries in India, the United Kingdom, the United States, and Canada. It dwells upon the use and importance of assistive technologies in general and their use for visually challenged learners in particular. Further, it gives suggestions for implementing assistive technologies in academic libraries for making visually challenged students self-reliant learners in accomplishing their academic and research pursuits. The present study adopted convenience sampling for collecting the data, which was collected between December 15, 2012 and January 18, 2013. PMID- 25112056 TI - Homebirth and the microbiome. PMID- 25112057 TI - Tricks of the trade. PMID- 25112058 TI - Marion's message: birth and the human future. PMID- 25112059 TI - Coming to twins. PMID- 25112060 TI - Why all the fuss about twins? PMID- 25112061 TI - The wonderful world of twin birth. PMID- 25112062 TI - The voice of reason. PMID- 25112063 TI - Twin birth in rural Nevada. PMID- 25112065 TI - Maternal placentophagy as an alternative medicinal practice in the postpartum period. PMID- 25112064 TI - Helping a mother with twins: choose your words wisely. PMID- 25112066 TI - In memory of Marsden Wagner. A friend to midwives, 1930-2014. PMID- 25112067 TI - Zachary and Jack. PMID- 25112068 TI - Jade and Cole. PMID- 25112069 TI - Rose and Philippa. PMID- 25112070 TI - Temperance and Genevieve. PMID- 25112072 TI - GBS updates from a homebirth perspective. PMID- 25112071 TI - Catharina Schrader: a midwife of 18th-century Friesland. PMID- 25112073 TI - Easing afterpains: wisdom from the Midwives College of Utah. PMID- 25112074 TI - Utilizing chiropractic for optimal pregnancy and birth outcomes. PMID- 25112075 TI - Moving from independent midwifery to a consultation service. PMID- 25112076 TI - Belly buddies. PMID- 25112077 TI - From Robin Lim in the Philippines. PMID- 25112078 TI - Is there a time or circumstance in the 3rd stage of labor when it is appropriate to massage the fundus? PMID- 25112079 TI - What are your comfort tips for 1st or 2nd stage labor? PMID- 25112080 TI - [Comparison of efficacy on functional constipation treated with electroacupuncture of different acupoint prescriptions: a randomized controlled pilot trial]. AB - OBJECTIVE: To evaluate preliminarily the efficacy on functional constipation treated with electroacupuncture of different acupoint prescriptions. METHODS: One hundred and four patients were randomized into a front-mu and back-shu points group (19 cases), a he-sea points group (34 cases), a he-sea, front-mu and back shu points group (26 cases) and a western medication control group (25 cases). In the front-mu and back-shu points group, electroacupuncture was applied at bilateral Tianshu (ST 25) and Dachangshu (BL 25). In the he-sea points group, electroacupuncture was applied at bilateral Quchi (LI 11) and Shangjuxu (ST 37). In the he-sea, front-mu and back-shu points group, electroacupuncture was applied at unilateral Tianshu (ST 25), Dachangshu (BL 25), Quchi (LI 11) and Shangjuxu (ST 37). In the three groups above, the treatment was given 5 times a week in the first two weeks and 3 times a week in the next two weeks. In the western medication control group, mosapride citrate tablets were prescribed for oral administration, 1 table (5 mg) each time, 3 times a day, continuously for 4 weeks. The period of research was 9 weeks, including 1 week for baseline evaluation, 4 weeks for treatment and 4 weeks for follow-up. The weekly defecation frequency was taken as primary index, while the defecation difficulty and life quality score were taken as the secondary indices for the efficacy evaluation after treatment and in follow-up. RESULTS: According to the intention to-treat (ITT) analytic principle, 104 cases were all enrolled in the final analysis. (1) After treatment, the weekly frequency of defecation was all increased significantly in the four groups (P < 0.05, P < 0.01). The efficacy of the three electroacupuncture groups was similar to that of western medication control group (P > 0.05). In follow-up, the increasing effect on the weekly frequency of defecation was maintained in the he-sea points group (P < 0.01), superior to the front-mu and back-shu points group and the western medication control group (P < 0.05, P < 0.01); the weekly frequency of defecation was not improved in the rest three groups (P > 0.05). (2) After treatment, defecation difficulty was relieved in the he-sea points group, the he-sea, front-mu and back shu points group and the western medication control group (P < 0.05, P < 0.01). In follow-up, the improvements were still significant in the he-sea points group and the he-sea, front-mu and back-shu points group (both P < 0.01). (3) After treatment, the life quality score was significantly improved in the patients of the he-sea points group (P < 0.05). The difference was not significant in the rest three groups as compared with that before treatment (all P > 0.05). CONCLUSION: The weekly frequency of defecation is increased effectively after treatment in the three electroacupuncture groups and the efficacy is similar to mosapride citrate tablets. The bilateral Quchi (LI 11) and Shangjuxu (ST 37) in he-sea acupoints increase significantly the weekly frequency of defecation, relieve defecation difficulty and improve life quality. Acupuncture efficacy is sustained for 4 weeks. This acupoints prescription is the best in the treatment of functional constipation. PMID- 25112081 TI - [Clinical efficacy observation of acupuncture at suliao (GV 25) on improving regain of consciousness from coma in severe craniocerebral injury]. AB - OBJECTIVE: To compare the clinical therapeutic effects differences between acupuncture at Suliao (GV 25) and Shuigou (GV 26) on promoting regain of consciousness from coma in severe craniocerebral injury. METHODS: Based on regular emergency treatments of neurosurgery, eighty-two cases of craniocerebral injury who were under stable condition were randomly divided into an observation group (42 cases) and a control group (40 cases). Suliao (GV 25) was selected as main aupoint, while Laogong (PC 8) and Yongquan (KI 1), etc. were selected as adjuvant acupoints and Neiguan (PC 6), Sanyinjiao (SP 6), Yifeng (TE 17) and Wangu (GB 12), etc. were selected as matching acupoints in the observation group where a strong needle manipulation was applied to improve the regain of consciousness. The main acupoint of Shuigou (GV 26) along with identical adjuvant acupoints and matching acupoints in the observation group were selected in the control group with identical strong needle manipulation. The treatment was given once a day in both groups, five times per week and ten times were considered as one session. The immediate clinical symptoms after acupuncture at Suliao (GV 25) and Shuigou (GV 26) were observed as well as Glasgow coma scale (GCS) before the treatment, after 45 days and 90 days of treatment to assess the resuscitation time and rate. Also the clinical efficacy was compared between both groups. RESULTS: The occurrence rate of sneezing reflex was 85.7% (36/42) in the observation group, which was higher than 25.0% (10/40) in the control group (P < 0.01). The average resuscitation time was (64.6 +/- 19.4) days in the observation group, which was obviously shorter than (73.8 +/- 14. 6) days in the control group (P < 0.05). The resuscitation rate was 88.1% (37/42) in the observation group, which was similar to 75.0% (30/40) in the control group (P > 0.05). Compared before the treatment, GCS were both improved after the treatment in two groups (both P < 0.01). The 90-day GCS was 9.52 +/- 2.32 in the observation group, which was superior to 8.47 +/-2.14 in the control group (P < 0.05). The curative and markedly effective rate was 45.2% (19/42) in the observation group, which was superior to 22.5% (9/40) in the control group (P < 0.05). CONCLUSION: The effect of acupuncture at Suliao (GV 25) on improving regain of consciousness from coma in severe craniocerebral injury is positive. It could specifically improve sneezing reflex and stimulate respiratory center, which has more obvious effect than acupuncture at Shuigou (GV 26). PMID- 25112082 TI - [Stroke-induced acroparalysis treated with xunjingcuiqi needling technique: a randomized controlled trial]. AB - OBJECTIVE: To observe the impacts on the muscle strength in the patients of stroke-induced acroparalysis treated with Xunjingcuiqi needling technique. METHODS: One hundred patients were randomized into a Xunjingcuiqi group and a routine acupuncture group, 50 cases in each group. In the routine acupuncture group, the routine acupuncture technique was adopted at the main acupoints, such as Shangxing (GV 23), Baihui (GV 20), Dicang (ST 4), Quchi (LI 11), Huantiao (GB 30) and Zusanli (ST 36), etc. In Xunjingcuiqi group, on the basis of the routine acupuncture technique, Xunjingcuiqi needling technique (pricking technique was quickly applied with the filiform needle along the running course of meridian to promote the conduction of meridian qi) was added. For the patients being hard to feel the needling sensation and with the muscle strength of 0 to 1 degree, Dongzhencuiqi technique was supplemented at shu-stream points of yang meridians (after qi arrival, the needling manipulation with limb movement was given to promote the conduction of meridian qi). The treatment was given once every day in the two groups. Ten treatments made one session. Three sessions of treatment were required. At the end of each session treatment, the muscle strength and clinical efficacy were assessed. RESULTS: In the 1st, 2nd and 3rd sessions of treatment, 20, 24 and 36 cases achieved the 3 to 5 degrees muscle strength in Xunjingcuiqi group, respectively; and 6, 10 and 15 cases achieved the 3 to 5 degrees muscle strength in the routine acupuncture group. The differences were significant statistically in comparison of the two groups (P < 0.01, P < 0.05). The markably effective rates were 60.0% (30/50), 64.0% (32/50) and 70.0% (35/50) after the 1st, 2nd and 3rd sessions of treatment in Xunjingcuiqi group, respectively; and those were 38.0% (19/50), 44.0% (22/50) and 46.0% (23/50) in the routine acupuncture group, respectively. The differences were significant in the 1st and 3rd sessions of treatment between the two groups (both P < 0.05). CONCLUSION: Xunjingcuiqi needling technique combined with routine acupuncture achieves the apparent superior efficacy on acroparalysis induced by ischemic stroke as compared with the simple routine acupuncture. Xunjingcuiqi needling technique obviously improves muscle strength and shortens the duration of sickness. PMID- 25112083 TI - [Clinical observation on medulla oblongata palsy after brainstem infarction treated with electroacupuncture at eight-neck-occiput points]. AB - OBJECTIVE: To compare the differences in the efficacy on speech and swallowing dysfunction of medulla oblongata palsy (MOP) after brainstem infarction between electroacupuncture at eight-neck-occiput points and routine acupoints. METHODS: Seventy-two patients were randomized into a neck-occiput points group and a meridian points group, 36 cases in each one. In the neck-occiput points group, the eight-neck-occiput points (Neck 1-4 points, Occiput 1-4 points) were selected. In the meridian points group, Lianquan (CV 23), Futu (LI 18), Tongli (HT 5), Hegu (LI 4) and the others were selected. Electroacupuncture was used in the two groups, dense-dispersion wave, retaining for 30 min. The treatment was given once a day, 5 treatments a week. Totally, 4 weeks were required. The symptom scores of speech and swallowing dysfunction were observed before and after treatment in the two groups. The efficacy was compared between the two groups. RESULTS: The scores of speech and swallowing dysfunction were improved significantly after treatment in the two groups (P < 0.05, P < 0.01). The results in the neck-occiput points group were better than those in the meridian points group (both P < 0.01). The curative rate of speech dysfunction was 30.6% (11/36) and that of swallowing dysfunction was 22.2% (8/ 36) in the neck-occiput points group, which were better than 11.1% (4/36) and 5.6% (2/36) in the meridian points group, respectively. The differences were significant in comparison of the two groups (P < 0.01, P < 0.05). CONCLUSION: Electroacupuncture at eight-neck-occiput points achieves a better efficacy on speech and swallowing dysfunction of MOP after brainstem infarction as compared with the routine acupoints. This therapy is characterized as more accurate point localization and safer operation. PMID- 25112084 TI - [Controlled observation of the efficacy on motion sickness in the prevention and treatment with jianpixingnao needling therapy]. AB - OBJECTIVE: To verify the efficacy of Jianpi-xingniao needling therapy on prevention and treatment of motion sickness. METHODS: Sixty volunteers of motion sickness were randomized into an acupuncture group and a delayed acupuncture group, 30 cases in each one. In the acupuncture group, acupuncture was given at Baihui (GV 20), Sishencong (EX-HN 1), Neiguan (PC 6), Zusanli (ST 36) and Hegu (LI 4). The needles were retained for 20 min. The treatment was given twice a week and 10 treatments were required. In the delayed acupuncture group, acupuncture was postponed, meaning no acupuncture during observation stage. Graybel scale was adopted to observe the score of symptoms and physical signs of the subjects of motion sickness before and after intervention. The efficacy was compared between the two groups. RESULTS: Twenty-five cases in the acupuncture group and 22 cases in the delayed acupuncture group were included in the statistical analysis. The score of symptoms and physical signs of motion sickness was reduced significantly after treatment in the acupuncture group as compared with that before treatment (10.12 +/- 3.37 vs 0.92 +/- 0.40, P < 0.05). The score in the acupuncture group was lower apparently than that in the delayed acupuncture group (0.92 +/- 0.40 vs 9.86 +/- 2.53, P < 0.05). The difference was not significant before and after treatment in the self-comparison of the delayed acupuncture group (P > 0.05). The total effective rate was 96.0% (24/25) in the acupuncture group, which was significantly better than 0.0% (0/22) in the delayed acupuncture group (P < 0.01). CONCLUSION: Jianpixingniao needling therapy relieves the symptoms of motion sickness in the patients and achieves a better clinical efficacy. PMID- 25112085 TI - [Efficacy observation on acupuncture for essential hypertension of yin deficiency due to yang hyperactivity pattern]. AB - OBJECTIVE: To observe the clinical effects of essential hypertension treated with acupuncture at Siguan [Hegu (LI 4) and Taichong (LR 3)], Quchi (LI 11) and Xingjian (LR 2). METHODS: Sixty cases of essential hypertension were randomly divided into an acupuncture group and a medication group, 30 cases in each group. Two groups of acupoint, which were (1) Siguan [Hegu (LI 4) and Taichong (LR 3)] and (2) Quchi (LI 11), Xingjian (LR 2), were selected alternatively in the acupuncture group, once everyday. In the medication group, captopril was prescribed for oral administration 25 mg per time, three times per day. Seven days made one session in both groups and totally three sessions were required. RESULTS: (1) After treatment, the blood pressure were decreased significantly in the two groups (all P < 0.01). Compared with the medication group, the diastolic pressure after 14 days, 21 days of treatment in the acupuncture group was decreased significantly (both P < 0.01). (2) In the terms of TCM syndrome score, the improvement of dizziness, soreness and weakness of waist and knees, palpitations was significant in the acupuncture group compared with that in the medication group(all P < 0.05). (3) The acupuncture group had less adverse reactions compared with the control group (P < 0.05). CONCLUSION: Acupuncture at Hegu (LI4) and Taichong (LR 3), Quchi (LI 11) and Xingjian (LR 2) can effectively decrease blood pressure; the effect of controlling diastolic pressure is better than captopril. It can also improve the symptoms of dizziness, soreness and weakness of waist and knees, and palpitations. PMID- 25112086 TI - [Efficacy observation on chrondromalacia patellae treated with fire needling technique at high stress points]. AB - OBJECTIVE: To compare the clinical efficacy differences between fire needling technique of filiform needle at high stress points and regular acupuncture on chrondromalacia patellae so as to provide the better therapy for the treatment of this disease. METHODS: Sixty cases of chrondromalacia patellae were randomized into a fire needling group (28 cases) and a routine acupuncture group (32 cases). In the fire needling group, 5 to 6 high stress points were localized according to the symptoms, palpation and imaging condition and were stimulated with fire needling technique of filiform needle. The treatment was given once every two days, 5 treatments made one session. In the routine acupuncture group, the regular acupuncture was applied at Dubi (ST 35), Xiguan (LR 7), Yanglingquan (GB 34), Yinlingquan (SP 9), Zusanli (ST 36), etc. The treatment was given once every day, 5 treatments made one session. Lysholm score, VSA score, patella title angle (PTA) and lateral patella angle (LPA) of the affected knees before and after treatment, as well as the clinical efficacy after treatment were observed in the two groups. RESULTS: After treatment, Lysholm score, VSA score, PTA and LPA were all improved apparently in the two groups (all P < 0.01). After the treatments, the improvements in Lysholm score, VSA score, PTA and LPA in the fire needling group were more obvious than those in the routine acupuncture group (all P < 0.05). The effective rate was 92.9% (26/28) in the fire needling group, better than 87.5% (28/32) in the routine acupuncture group (P < 0.01). CONCLUSION: The fire needling technique of filiform needle at the high stress points relieves the clinical symptoms of chrondromalacia patellae and recovers the biodynamical structure of patellae. PMID- 25112087 TI - [Clinical study on primary osteoporosis treated with spreading moxibustion for warming yang and activating blood circulation]. AB - OBJECTIVE: To observe the efficacy on primary osteoporosis treated with spreading moxibustion for warming yang and activating blood circulation so as to provide the effective clinical therapeutic methods for osteoporosis. METHODS: Sixty cases of primary osteoporosis were randomized into a spreading moxibustion group (30 cases) and a calcium tablet group (30 cases). In the calcium tablet group, caltrate was prescribed for oral administration, 600 mg per day. In the spreading moxibustion group, on the basis of the treatment as the calcium tablet group, the spreading moxibustion was applied at Dazhui (GV 14) to Yaoshu (GV 2) for warming yang and activating blood circulation. The duration of treatment was 12 weeks. Visual analogue scale (VAS) score, TCM clinical symptom score and bone mineral density (BMD) were observed and compared before and after treatment in the patients between the two groups. RESULTS: VAS scores were reduced apparently after treatment in the two groups (both P < 0.01) and the results in the spreading moxibustion group were obviously superior to that in the calcium tablet group (2.36 +/- 0.43 vs 4.52 +/- 0.35, P < 0.01). BMD were all increased in the two groups (P < 0.05, P < 0.01) and the results in the spreading moxibustion group were superior to those in the calcium tablet group (both P < 0.05). The total clinical effective rate was 86.67% (26/30) in the spreading moxibustion group, apparently better than 63.33% (19/30) in the calcium tablet group (P < 0.05). TCM clinical symptom scores after treatment were all reduced apparently in the two groups (both P < 0.01), and the result in the spreading moxibustion group was obviously superior to that in the calcium tablet group (4.72 +/- 1.90 vs 6.82 +/- 2.30, P < 0.01). The total effective rate of TCM symptoms was 93.33% (28/30) in the spreading moxibustion group, apparently better than 70.00% (21/30) in the calcium tablet group (P < 0.05). CONCLUSION: The combined therapy of spreading moxibustion for warming yang and activating blood circulation and the oral administration of caltrate apparently relieves pain and TCM clinical symptoms, improves BMD in the patients of osteoporosis and achieves definite clinical efficacy in the patients of osteoporosis. PMID- 25112088 TI - [Dragon moxibustion for 32 cases of low back muscle fasciitis]. PMID- 25112089 TI - [Discussion on disease spectrum treated with acupuncture at shenmen (HT 7) and its compatibility based on bibliometrics]. AB - The modern literatures on the diseases treated with acupuncture at Shenmen (HT 7) were collected. Using literature statistical analysis in bibliometrics, the common compatibility of Shenmen (HT 7) and the disease spectrum were analyzed so as to provide the references of the diseases that can be treated with acupuncture at Shenmen (HT 7). It was found that 39 kinds of diseases and symptoms, mainly nerve system disedses, could be treated with acupuncture at Shenmen (HT 7), including insomnia, depression, anxiety and dementia. Shenmen (HT 7) was seldom used alone. Instead, it was commonly used along with Baihui (GV 20), Sanyinjiao (SP 6), Neiguan (PC 6), Sishencong (EX-HN 1) and Taicong (LR 3). PMID- 25112090 TI - [Analysis on clinical palpation laws of muscle meridian focus in scapulohumeral periarthritis]. AB - OBJECTIVE: To explore the distribution rules of proximal and distal focus of muscle meridian region in scapulohumeral periarthritis. METHODS: Three hundred and six shoulder joints of affected side were selected in 216 patients of scapulohumeral periarthritis. Under the guidance of muscle meridian theory, with the anatomical characteristics of muscle meridian focuses, the frequency and location where proximal and distal focus appeared were calculated by palpation. RESULTS: The percentages of the frequency that the focus of muscle meridian of Hand-Yangming, Hand-Shaoyang, Hand-Taiyang, and three yin meridians of hand appeared at proximal points of shoulder joint were 25.6% (1 146/5 657), 30.9% (1 749/5 657), 19.0% (1 075/5 657), and 24.5% (1 387/5 657), respectively, the focuses of muscle meridian region were Jianyuci, Juguci, Xiaoshuoci, Naohuici, etc. The percentages of the frequency that the focus of muscle meridian region appeared at distal points of shoulder joint were 31.77% (287/905), 23.2% (210/905), 10.9% (99/905), and 34.1% (304/905), the focuses of muscle meridian were Yangxici, Shousanlici, Yangchici, etc. CONCLUSION: The location and frequency of proximal and distal focus of muscle meridian in scapulohumeral periarthritis are closely related with the anatomical structure and biomechanical characteristics of the shoulder joints, thus new therapy for scapulohumeral periarthritis is implied. PMID- 25112091 TI - [A secondary discussion on acupoint characteristic]. AB - With references of historical materials and modern literature regarding acupoint characteristic, a secondary analysis on the concept, origin, related factors and research methods in present research of acupoint characteristic is performed. The acupoint characteristic should be considered as an acupoint inherent attribute that could explain physiological and pathological manifestations at the same time, including location attribute and function attribute, which is related with time and treatment method. Some re-thinking on acupoint characteristic is proposed as well as advice on further research method and direction, hoping to promote the research development of acupoint characteristic. PMID- 25112092 TI - [Fire needle combined with small needle-knife for 58 cases of chronic lumbar muscle strain]. PMID- 25112093 TI - [Effects of controllable dynamic inhaled exposure of moxa smoke on LDL-r, ICAM-1 and morphology of heart tissue in rats]. AB - OBJECTIVE: To observe the change of lipid metabolism and vascular endothelium as well as morphology of heart tissue in rats who were long-time exposed to moxa smoke with different concentrations in order to provide reference for safety assessment of moxa smoke on cardiovascular system. METHODS: One hundred and sixty eighty Wistar rats were randomly divided into a control group, a low concentration group, a median-concentration group and a high-concentration group, 42 rats in each one. The rats were exposed to moxa smoke with concentration of 0%, 10%, 40% and 70%, respectively, for 20 min per day. After continuous intervention for six months, enzyme-linked immunosorbent assay (ELISA) was applied to measure the level of low density lipoprotein-receptor (LDL-r) and intercellular adhesion molecule-1 (ICAM-1) in blood serum in each group; the slices of heart tissue were stained with hematoxylin-eosin staining method to observe morphology change of heart tissue. RESULTS: (1) After the intervention of moxa smoke, the levels of LDL-r and ICAM-1 in the low-concentration group were not statistically different from those in the control group (both P > 0.05); the level of LDL-r in the median-concentration group was significantly increased, which was statistically different from that in the control group [(3.87 +/- 0.27) mg/mL vs (2.12 +/- 0.13) mg/mL, P < 0.01], however, the content of ICAM-1 was not obviously changed; although the level of LDL-r in the high-concentration group was presented with an escalating trend, it was not statistically different from that in the control group (P > 0.05) while the level of ICAM-1 was obviously increased (P < 0.01). (2) Under the light microscope, the abnormalities of cardiac muscle fibers and myocardial cell in each group were not been observed. CONCLUSION: The long-time intervention of low-concentration moxa smoke has no significant effects on lipid metabolism and vascular endothelium of rats, indicating that clinical application of low-concentration moxa smoke is relatively safe. The long-time intervention of moderate-concentration moxa smoke could significantly increase the clearance rate of cholesterol, implying the beneficial regulation of moxa smoke on lipid metabolism. The high-concentration moxa smoke could induce certain damage to vascular endothelium but its mechanism is in need of further research. The pathologic change of heart tissue could not be induced by moxa smoke with any concentration. PMID- 25112094 TI - [Effects of electroacupuncture with manifestation-root acupoint combination on ultrastructure and biosynthesis in mitochondrial of quadriceps femoris in rats with insulin resistance]. AB - OBJECTIVE: To explore the mechanism of electroacupuncture on improving insulin resistance of rat from aspects of morphology and function of mitochondrial in quadriceps femoris. METHODS: Forty-eight 8-week Wistar rats (female and male in half) were randomly divided into a normal group (16 rats, group A), a model control group (16 rats, group B), a model plus electroacupuncture (EA) group (8 rats, group C) and a model plus sham acupoint EA group (8 rats, group D). Group A was given with basic diet while high-fat diet was applied in the group B, group C and group D for 8 weeks to establish model of insulin resistance. After the model establishment, "Guanyuan" (CV 4), "Zhongwan" (CV 12), "Zusanli" (ST 36) and "Fenglong" (ST 30) were selected according to acupoint combination of manifestation-root in the group C, while four points in non-meridian area where 1 to 2 mm next to the acupoints used in group C were selected in the group D. The treatment was given 15 min per time with 1 mA of intensity and 2 Hz in frequency, 5 times per week for totally 8 weeks. The transmission electron microscope was adopted to observe mitochondria structure, and chemical colorimetry was used to test the activity of adenosine triphosphate (ATP) synthase and phosphomolybdic acid colorimetry was applied to measure the content of ATP. RESULTS: After the treatment, the body mass was (401.63 +/- 109.81) g in the group B, which was significantly higher than (305.88 +/- 62.72) g in the group A (P < 0.05); morphological structure of mitochondrion was damaged, showing swelling and deformation; the activity of ATP synthase was decreased (P < 0.05) and the content of ATP in tissue of quadriceps femoris was also obviously lowered (P < 0.05). The body mass was (294.13 +/- 53.78) g in the group C, which was significantly lower than that in the group B (P < 0.05); the damaged mitochondrion was restored and merged among each other; the activity of ATP synthase was increased (P < 0.05); the content of ATP in tissue of quadriceps femoris was obviously lifted (P < 0.05). The results in group D were not different from those in group B. CONCLUSION: The electroacupuncture with manifestation-root acupoint combination could improve the recovery of damaged structure of mitochondrion and promote the merge among each other, which could enhance oxidizing capacity, lower body mass and improve synthetic rate of ATP. PMID- 25112095 TI - [Ninety-one cases of intractable hiccups treated by acupuncture of relaxing the bowels and keeping the adverse stomach-qi downswards]. PMID- 25112096 TI - [Low back pain of cold-damp pattern treated with electric-thermal Bian-stone therapy and traditional moxibustion: a randomized controlled trial]. AB - OBJECTIVE: To compare the difference in the efficacy on low back pain of cold damp pattern between electric-thermal Bian-stone therapy and moxibustion box therapy. METHODS: Forty-one cases of low back pain of cold-damp pattern were randomized into an electric-thermal Bian-stone therapy group (group A, 26 cases) and a box moxibustion therapy group (group B, 15 cases). In the group A, the electric-thermal Bian-stone was placed over Shenshu (BL 23) and Weizhong (BL 40). The temperature of stone was adjusted in accordance with patient's comfort. In the group B, moxibustion box was used over Shenshu (BL 23) and Weizhong (BL 40). The treatment was given once every day or every two days. Ten treatments made one session. The symptom and physical signs score of low back pain and the score of cold-damp syndrome were observed before and after treatment in the patients. RESULTS: The symptom and physical signs score of low back pain and the score of cold-damp syndrome were all improved in the two groups (all P < 0.01). The changing rate of symptom and physical signs and syndrome were (37.04 +/- 32.68)% and (22.85 +/- 29.95)% in the group A, and were (47.29 +/- 22.08)% and (23.89 +/- 22.53)% in the group B, respectively, without significant difference in comparison between the two groups (all P > 0.05). CONCLUSION: The efficacy on low back pain of cold-damp pattern treated with the electric-thermal Bian-stone therapy is similar to that of moxibustion box therapy. This therapy is characterized as more convenient, safer operation and less pollution. PMID- 25112098 TI - [Fire-needle with sulfur for 40 cases of epidemic parotitis]. PMID- 25112097 TI - [Acupuncture combined with moxibustion for 32 cases of anal pain after anus operation]. PMID- 25112099 TI - [The enlightenment of Fu's subcutaneous needling on pain medicine]. AB - Fu's subcutaneous needling (FSN) is a modern approach developed from traditional Chinese acupuncture. It could give some stimulation in the subcutaneous region that has a quick and long-lasting effect on soft tissue injuries and some of the internal medicine diseases. It is a safe approach without adverse reaction. Through analysis of the features and possible mechanism of FSN, it is believed that research on mechanism of FSN is beneficial to the development of modern medicine, especially to pain management. PMID- 25112100 TI - [Acupuncture combined with Tuina for 10 cases of sacroiliac joint sclerosing osteitis]. PMID- 25112101 TI - [Present situation and development of acupuncture and moxibustion in Turkey]. AB - The development and status of acupuncture-moxibustion in Turkey in the fields of education, legal establishment, treatment, etc. are introduced. There are four distinguished features of acupuncture-moxibustion development in Turkey: (1) The geographical position of the country as the link of Europe and Asia, has resulted in the special feature of acupuncture-moxibustion transmission and development. It combines both the traditional theories from the East and the modified and modern techniques from the West. (2) The combination of theories and clinical practice started when acupuncture-moxibustion was first introduced. (3) The application of acupuncture-moxibustion has gone through a process from spontaneous transmission among the people to legalization by the government, from disorderly to orderly, and from market behavior to government-lead regulation, which has powerfully promoted healthy development of the medicine. (4) Acupuncture-moxibustion education provided by registered universities has guaranteed the quality of the education itself and the competency of the professionals. It has raised the scientific and normative character of application and increased the credibility of the people, and also has ensured the sustainability of acupuncture-moxibustion development by providing qualified professionals. PMID- 25112102 TI - [Case of Raynaud disease]. PMID- 25112103 TI - [Quality assessment on guidelines of clinical practice in acupuncture and moxibustion: a study based on AGREE]. AB - The quality of guidelines of clinical practice in acupuncture and moxibustion was evaluated with AGREE II tool. After retrieval of officially-issued guidelines of clinical practice in acupuncture and moxibustion from 2004 to 2013, totally 5 types of evidence-based guidelines of clinical practice in acupuncture and moxibustion were acquired, including depression, herpes zoster, pseudobulbar palsy after stroke, migraine and Bell's palsy. With AGREE II tool, independent score in six areas, including guideline's scope and purpose, participants and personnel, preciseness, clarity and readability, applicability and editorial independence were analyzed to perform a comprehensive evaluation in the end. The assessment results indicated that the score of editorial independence in evidence based guidelines of clinical practice in acupuncture and moxibustion was the highest, averagely 97.9%, which was followed by clarity and readability (83.3%), participants and personnel (78.1%), preciseness (75.6%), the scope and purpose (68.1%) and the applicability (62.5%). The total evaluation score was all 6 points in the five guidelines with recommended as comprehensive evaluation advice. This study results indicate that although the guideline of clinical practice in acupuncture and moxibustion is low in number, the total quality is considerable. PMID- 25112104 TI - [A further discussion on acupuncture treatment plan of facial neuritis in Evidence-based Guidelines of Clinical Practice in Acupuncture and Moxibustion]. AB - The treatment plan of facial neuritis in Evidence-based Guidelines of Clinical Practice in Acupuncture and Moxibustion (2011 edition) is discussed, and case information of facial neuritis during the recent five years in department of acupuncture and moxibustion, PLA General Hospital, is retrospectively analyzed. In accordance with anatomy of the facial nerve to form the acupuncture prescription, the detailed diagnosis and treatment method for facial neuritis are introduced. The advantages of the diagnosis and treatment method for facial neuritis are summarized, hoping to establish a more comprehensive, standardized and unified treatment plan. PMID- 25112105 TI - [Long snake moxibustion for 38 cases of gout]. PMID- 25112106 TI - [Origin and development of umbilical therapy in traditional Chinese medicine]. AB - The origin and development of umbilical therapy in traditional Chinese medicine is explored from related literature in the history. As a result, the Shang period is regarded as initial period of umbilical therapy, while periods from Han Dynasty, Jin Dynasty and Southern-Northern Dynasties to Sui Dynasty and Tang Dynasty could be taken as stage of primary development. Time from Song Dynasty, Jin Dynasty and Yuan Dynasty to Ming and Qing Dynasties is believed as mature stage. Also the manipulation, application principle, indications and contraindications of umbilical therapy are explained. A brief overview of modern development of umbilical therapy is also described. PMID- 25112107 TI - [Acupuncturists and their academic contributions in Lingnan area: a review]. AB - The academic thoughts of Lingnan acupuncture and moxibustion have been an essential part of Lingnan medicine. By exploration and arrangement of Lingnan medicine and books, journals and literatures regarding acupuncture and moxibustion, the ancient and modern acupuncturists and their academic contributions in Lingnan area were reviewed. As a result, the number of Lingnan acupuncturists and their works was low before Qing Dynasty, while from the Republic of China era to People's Republic of China, a considerable amount of acupuncturists emerged with quite a lot of works. By exploration and arrangement of Lingnan acupuncturists and their works and academic opinion, the acupuncture moxibustion school characterized by Lingnan could be formed and developed. PMID- 25112108 TI - [Discussion on professor SHAO Jing-Ming's academic opinion of focusing spirit]. AB - During professor SHAO Jing-ming's academic research and medical practice, his academic opinion of focusing spirit is gradually developed. In terms of nurturing the spirit, attention should be paid on persistence as well as everyday health maintenance and exercise to nurture the spirit of physician. In terms of clinical diagnosis and treatment, patients' psychology, employment and life status should be observed and experienced, which could bring more methods to take essential care of patients' spirit. The treatment should work with psychological counseling, advocating that based on patients' qi and spirit, various forms of treatment methods should be properly used, such as acupuncture or moxibustion or combination of acupuncture and medicine, along with simple acupoint selection and harmony medication. Before clinical treatment of acupuncture, calming the mind is critically emphasized to make a clear diagnosis. During the acupuncture, calming and focusing the mind is necessary as well as emphasizing the details, so acupuncture could be integrated with Chi Gong to create a new warming-sensation technique. In a word, the academic opinion of focusing spirit is shedding an inspiring light upon further study. PMID- 25112109 TI - [Case of lacrimal duct obstruction]. PMID- 25112110 TI - [Twenty cases of spinocerebellar atrophy treated by multi-needling in rows at occiput]. PMID- 25112111 TI - [Clinical randomized controlled trials of acupoint catgut-embedding for simple obesity: a meta-analysis]. AB - The clinical therapeutic effect of acupoint catgut-embedding for simple obesity was systemically analyzed to provide reference and assistance for its clinical treatment and research. By searching in the CBM, CNKI, VIP, Wanfang, Pubmed, Springer and Medline databases, clinical randomized controlled trials (RCT) of acupoint catgut-embedding for simple obesity published from Jan, 2009 to July, 2013 were collected while Revman 5. 2 software was applied to perform the Meta analysis. Totally 19 articles were acquired with 1 658 cases involved. The effective rate was selected as primary outcome measure in 19 articles. The Meta analysis was performed among homogeneous researches. The results indicated that compared with other therapies, pooled OR of acupoint catgut-embedding was 2.45 with 95% CI [1.81, 3.32]; in the test for overall effect, Z = 5.81, implying the efficacy difference of two therapies was significant in the treatment of simple obesity (P < 0.01). In subgroups analysis, in the event of treatment session with more than 3 months, compared with other therapies, pooled OR of acupoint catgut embedding was 2.61 with 95% CI [1.53, 4.46]; in test for overall effect, Z = 3.51, implying the efficacy difference of two therapies was significant in the treatment of simple obesity (P < 0.01); in the event of treatment session with less than 3 months, compared with other therapies, pooled OR of acupoint catgut embedding was 2.38 with 95% CI [1.65, 3.44]; in test for overall effect, Z = 4.46, implying in the treatment of simple obesity the efficacy difference of two therapies was significant (P < 0.01). Compared with electroacupuncture, OR of acupoint catgut-embedding was 1.79, 95% CI [1.08, 2.95] (P = 0.02). Compared with acupuncture, OR of acupoint catgut-embedding was 1.89, 95% CI [1.16, 3.09] (P = 0.01), which explained that compared with electroacupuncture and acupuncture, the efficacy of acupoint catgut-embedding was significantly different. In a word, the clinical efficacy of acupoint catgut-embedding is superior to other therapies in the treatment of simple obesity. PMID- 25112112 TI - [Clinical utility of reflectance confocal microscopy for the non-invasive diagnosis of lentigo maligna melanoma]. AB - BACKGROUND: Lentigo maligna melanoma (LMM), a melanoma subtype that arises on sun damaged facial skin, is difficult to diagnose clinically. Patients and physicians are reluctant to perform unnecessary facial biopsies. Reflectance confocal microscopy (RCM) is a novel technique for non-invasive skin imaging at cellular level resolution. RCM increases the accuracy of melanoma diagnosis. AIMS: To describe the diagnostic utility of RCM in cases of clinically and dermatoscopically equivocal pigmented skin lesions suspicious for LMM. METHODS: This is a retrospective case series derived from the population of patients undergoing periodic skin cancer screening at a tertiary hospital clinic that specializes in skin cancer diagnosis. All patients consented to RCM imaging as an ancillary test prior to the decision on performing a biopsy in the facial lesion. RESULTS: We report on four patients who presented clinically and dermatoscopically equivocal pigmented skin lesions in the head and neck region, with differential diagnosis of LMM. Furthermore, in two patients, a prior incisional biopsy indicated a benign diagnosis upon histopathological analysis. In all cases, RCM examination showed specific criteria for LMM. The RCM diagnosis of LMM allowed direct referral for excisional surgery in three patients. In another patient, RCM findings guided incisional biopsy-site selection to a focus that revealed histopathology clear-cut criteria for LMM. CONCLUSIONS: RCM is a very useful adjunct to the non-invasive diagnosis of LMM. PMID- 25112113 TI - [Cutis verticis gyrata as an early rare presenting sign of acromegaly]. AB - Cutis verticis gyrata (CVG) is a descriptive term for a dermal sign in which deep furrows and convoluted ridges are seen upon the scalp. They are formed due to thickening of the skin folds of the scalp and produce an appearance that resembles the gyri of the brain. The condition is classified primary when the etiology is unknown or neurologically based. CVG will be considered secondary when a definite cause, systemic or localized, is responsible for the sign. We describe a 34 year-old male who was presented with a one-month history of arthralgia in his interphalangeal joints. His physical examination revealed scalp changes compatible with CVG, which appeared 3 years earlier. Following a thorough investigation of the patient, acromegaly was diagnosed. Although CVG is a rare condition, it has been described in patients with acromegaly. The appearance of SVG as an early sign of acromegaly makes this case unique and important. In a patient developing CVG, acromegaly and other treatable disorders should always be excluded. PMID- 25112114 TI - [Peripheral arthritis in polymyalgia rheumatica]. AB - Polymyalgia rheumatica is characterized by aching and stiffness of the shoulder, the pelvic girdles and the neck. Peripheral joint involvement is less recognized by the medical community as a sign of the disease. In this article we present two patients whose disease was manifested by peripheral symptoms. The frequency, manifestations and the pathogenesis of the disorder are discussed and the importance of recognition of these symptoms and signs of the disease is stressed. PMID- 25112115 TI - [Unique mechanism in heart-shaped balloon burst resulting in blunt ocular injury]. AB - We have previously shown that heart-shaped balloons have a different explosion mechanism than spherical balloons in which the former splits into two rubber parts still attached to the balloon base with a backward whiplash motion. This backward whiplash motion may cause significant blunt ocular trauma if the balloon is inflated by mouth. In this article, the energy of the blunt ocular trauma is estimated by the high speed camera photos analysis of the balloon burst. Furthermore, we describe the followup of eight patients with ocular trauma following inflation of heart-shaped balloons. PMID- 25112116 TI - [Lentigo maligna: a diagnostic and therapeutic challenge]. AB - Lentigo maligna is an early type of melanoma which appears in sun damaged skin. The clinical diagnosis as well as the pathological diagnosis are a challenge to the clinician and the pathologist since atypical proliferation of melanocytes is a common finding in chronically sun exposed skin. The use of a dermatoscope and in vivo reflectance confocal microscopy as diagnostics aids can make the clinical diagnosis more accurate. Mohs micrographic surgery has become the standard of care, if available, for lentigo maligna. PMID- 25112117 TI - [Posterolateral rotatory instability of the elbow]. AB - The term posterolateral rotatory instability (PLRI) was coined in 1991 by O'Driscoll to describe the instability of the elbow caused by injury to the lateral ulnar collateral ligament (LUCL). This condition, which is usually preceded by a traumatic dislocation of the elbow, is the most common type of chronic instability of the elbow. In this type of instability, the radius and ulna rotate externally in relation to the distal humerus, leading to posterior displacement of the radial head relative to the capitellum. lateral elbow pain, clicking, popping and snapping are possible symptoms. The diagnosis of PLRI relies on a high index of suspicion and on a detailed physical examination. Several tests have been described including apprehension tests and examination under anesthesia. Surgical treatment with reconstruction of the lateral collateral ligament complex yields successful results. In this review we summarize the current knowledge of the pathoanatomy, presentation, physical examination, diagnostic tests and management of chronic posterolateral rotatory instability of the elbow. PMID- 25112118 TI - [Physical exercise for people with cerebral palsy: effects, recommendations and barriers]. AB - The management goal of cerebral palsy (CP) is improving functionality, locomotion and independence. Treatment programs commonly encompass adapted physical activity (APA). This review summarizes the knowledge regarding the effects and recommendations for APA in persons with CP. In addition, barriers to APA in this population are reviewed. The available literature on benefits of APA to persons with CP has focused mainly on youth. The components of the APA programs generally consist of strength, aerobic and flexibility training. There is no empirical evidence that strength-training increases spasticity in people with CP. Furthermore, strength-training may increase strength and the ability to perform daily activities. Aerobic-training is especially important as persons with CP typically have low cardiorespiratory fitness and high prevalence of cardiac disease. However, limited published evidence exists on aerobic-training effects in this population. Nonetheless, the evidence suggests that aerobic-training in persons with CP can improve physiological outcomes, yet the influence of these changes on participation has not been investigated sufficiently. Stretching exercise is a common treatment for spasticity. Surprisingly, there is inconclusive evidence for the effectiveness of stretching exercise for persons with CP. Despite the importance attributed to APA for people with CP, low levels of physical activity have been reported in this population. However, when caregivers perceive greater benefits of exercise, individuals with CP are more likely to be active. In contrast, barriers to APA include costs of APA programs, limited means of transportation to APA facilities, lack of information regarding APA facilities and limited appropriate exercising equipment in the APA facilities. PMID- 25112119 TI - [Breastfeeding and childhood leukemia and lymphoma]. AB - In the last 30 years there has been an increase in the incidence rate of childhood cancer in the western world. Although the 5-year survival rate from childhood cancer has increased significantly over the years due to advances in treatment technologies, cancer is still one of the leading causes of death among children in westernized countries. Leukemia and lymphoma are two of the most common cancer types in children and together account for about 45% of all childhood cancers. Nevertheless, very little is known of the etiology of childhood leukemia and lymphoma. Several studies had looked into the question of a relationship between infant nutrition--breastfeeding or lack thereof--and the risk of childhood leukemia and lymphoma as part of the "infective agent theory". This review aims to describe the current scientific evidence regarding the possible connection between breastfeeding and childhood malignancies, with an emphasis on childhood and adolescent leukemia and lymphoma. To that end, a systematic review of past studies has been conducted using Pubmed. Furthermore, the bibliographies of the relevant studies found on Pubmed were consulted. Studies were divided into two groups: original studies, and systematic reviews and meta analyses. Based on the Literature review, it is evident that the results are still inconclusive--some studies found a connection between breastfeeding and a lower risk of childhood leukemia and lymphoma, while others found no connection. The variability in breastfeeding and childhood cancer rates among the different populations where studies were conducted is large. In view of that variability and the differing results of former studies, there is a need to continue research. Israel, with characteristics of both a westernized country and a more traditional society with respect to parity and breastfeeding, is a good place to conduct such a study, with possible important implications for public health. PMID- 25112120 TI - [Consensus conferences as a tool for implementing national policy--a review and international comparison]. AB - The consensus conference (CC) is a professional methodology for comprehensive decision-making on controversial healthcare issues. The CC is based on health technology assessment, combining an in-depth review of the literature, consultation with experts and discussion within the framework of a broad panel of public and medical representatives. The process has many advantages but was also faces criticism; it reflects democratic deliberation, and reveals an opportunity to bridge the conceptual gap between policymakers and the public. The process enables citizens to be involved in decisions regarding unsolved medical dilemmas, as well as the means for resolving these questions, in an open transparent way. Those who criticize this mechanism refer to the restricted understanding of medical topics by lay-men, leading to only a negligible influence by nonmedical participants. However, the range of successful recommendations varies between countries. Many constraints raise the need for bending and matching the original model to different scenarios around the world; in the USA, an effort was made to preserve professional and academic principles, while in European countries flexibility led to evolving methodologies, and other frameworks developed. Currently, the most common methodology is the "citizen jury", empowering the participation of representatives of the public, as a mirror to preferences of the individual and society. Despite resistance, consensus conferences remain a successful model for policy-making in healthcare for over 30 years. During 2009 the method was even expended for global discussion involving representatives from 38 nations. PMID- 25112121 TI - [Spiritual care in hospitals and other healthcare settings in Israel--a profession in the making]. AB - Faced with a serious, incurable illness, disability, and other symptoms, both physical and mental, some patients find themselves wondering about the meaning of their Lives. They need the help of a professional who can perceive their mental turmoil and identify their spiritual needs, and who knows how to help them find meaning in their uncertain state. Spiritual care providers are professionals whose role it is to provide patients with support in their hour of need, to help them preserve their identity in life-threatening situations, and to help them re endow their world with meaning, employing a special language and set of tools that enable patients to get in touch with their spiritual resources and internal powers of healing. Spiritual care providers serve on the medical staff in Western countries. In the United States, some 2,600 are employed in general hospitals, psychiatric hospitals, long-term care facilities, and palliative care units. Approximately ten years ago, the profession began developing in Israel. Today, dozens of spiritual care providers are now working in the healthcare system. There is a spiritual care network with 21 member organizations. Although the profession is laying down roots in the healthcare system in this country, it is still in its infancy and has to contend with substantial barriers and challenges, including professional recognition, creating positions, and identifying sources of funding for positions. The profession still has much room to grow as it is further incorporated into the healthcare system and continues undergoing adaptation to the Israeli cultural setting. PMID- 25112122 TI - [Confidence interval calculation for small numbers of observations or no observations at all]. AB - Confidence interval calculation is a common statistics measure, which is frequently used in the statistical analysis of studies in medicine and life sciences. A confidence interval specifies a range of values within which the unknown population parameter may lie. In most situations, especially those involving normally-distributed data or large samples of data from other distributions, the normal approximation may be used to calculate the confidence interval. But, if the number of observed cases is small or zero, we recommend that the confidence interval be calculated in more appropriate ways. In such cases, for example, in clinical trials where the number of observed adverse events is small, the criterion for approximate normality is calculated. Confidence intervals are calculated with the use of the approximated normal distribution if this criterion is met, and with the use of the exact binomial distribution if not. This article, accompanied by examples, describes the criteria in which the common and known method cannot be used as well as the stages and methods required to calculate confidence intervals in studies with a small number of observations. PMID- 25112123 TI - [Tocophobia--its origin, prevalence and implications]. AB - Tocophobia is defined as fear from pregnancy in general and fear of vaginal delivery in particular. This is a relatively prevalent phenomenon, which originates due to traumatic events in the past: whether as a result of previous bad obstetric experience or from other non-obstetric related events. Unstable mental disorder may also be expressed as tocophobia. As there is no common agreement regarding the definition of tocophobia, conservative methods of treatment have not proven effective. Male tocophobia is also recognized and can be negatively influential on female males and spouses. The ultimate solution to tocophobia is an elective cesarean section following maternal request, with no obvious medical indication. This creates ethical problems to the attending physicians. PMID- 25112124 TI - [Clinical pathological conference: abdominal masses and purulent ascites]. AB - A 91 year old patient presented with constipation, abdominal distension, weakness and anorexia lasting for two days. Computed tomography revealed multiple peritoneal masses with significant growth within days and local invasiveness without regard to anatomical boundaries. No lymphadenopathy or hepatosplenomegaly were found. Abdominal paracentesis showed 60,000 cells/mm3 presumed to be neutrophils. During follow-up, there were no clinical or radiographic signs of peritonitis. Trans-abdominal true-cut biopsy from the peritoneal masses was consistent with diffuse large B cell lymphoma germinal center B cell type, clinically presenting as peritoneal lymphomatosis. FISH cytogenetic study identified single BLC-6 gene in the tumor infiltrating lymphocytes. We speculated that this aberration in the patient's immune system cells contributed to this rare, unusual and aggressive lymphoma presentation in an otherwise non-immune compromised patient. PMID- 25112125 TI - [Sick child, sick parents]. PMID- 25112126 TI - Has Jackson talken over our MSMA? PMID- 25112127 TI - Change of heart: transplantation in Mississippi. PMID- 25112128 TI - Axillary lymph node treatment in breast cancer: an update. AB - Sentinel lymph node biopsy (SLNbx) is the standard of care for staging of breast cancer. Patients with a negative sentinel lymph node biopsy (SLNbx) do not undergo axillary lymph node dissection (ALND) or regional nodal irradiation (RNI). However, if a patient has a positive sentinel lymph node biopsy (SLNbx), then axillary lymph nodal dissection (ALND) is the standard treatment. Recent studies, notably the Z-0011 and MA-20 trials, have demonstrated that omission of axillary lymph nodal dissection (ALND) did not decrease overall survival. MA-20 demonstrated that inclusion of regional nodal irradiation (RNI) in addition to axillary lymph nodal dissection (ALND) did increase survival when compared to axillary lymph nodal dissection (ALND) without regional nodal irradiation (RNI). Ongoing studies are randomizing patients to axillary lymph nodal dissection (ALND) or regional nodal irradiation (RNI) after a positive sentinel lymph node biopsy (SLNbx). PMID- 25112129 TI - Mississippi provisional reportable disease statistics. March 2014. PMID- 25112130 TI - Dr. W H. H. Lewis of Fayette (1866-1936). PMID- 25112131 TI - President's page. Thoughts on Medicaid expansion. PMID- 25112132 TI - A return to the Asclepeia: a physician's enduring obligation to his or her patients. PMID- 25112133 TI - Rationing vs. reengineering: the 21st century challenge for American health care. PMID- 25112134 TI - Sustainable access to data for postmarketing medical product safety surveillance under the amended HIPAA Privacy Rule. PMID- 25112135 TI - Privacy vs. progress: research exceptionalism is bad medicine. AB - Attitudes about privacy are changing in non-research settings, but these attitudinal shifts do not seem to be affecting the way regulators and ethicists think about the need to protect people from the risks of harm resulting from use of personal information in research studies (so-called "informational risks"). Increasingly, people routinely share personal information (including health information) online. And yet, a proposal has been made to restrict further the use of existing data, such as electronic medical records, for purposes of scientific research, even when personal identifiers have been removed. The disproportionate focus on "informational" risks in research is a form of research exceptionalism. This practice of treating research risks with greater caution than we treat other risks encountered in daily life is a legacy of past research abuses. Although understandable in historical context, this exceptionalism is harmful when it unreasonably interferes with scientific advances that could improve human health and welfare. PMID- 25112136 TI - Big data proxies and health privacy exceptionalism. PMID- 25112137 TI - Crossing 138: two approaches to churn under the Affordable Care Act. AB - A predicted side effect of the Medicaid expansion and state-based Exchanges under the Affordable Care Act is churn. Churn is the shifting into and out of eligibility for insurance affordability programs due to income changes. Because the line between Medicaid and Exchange eligibility is fine -138% of the federal poverty level -millions of Americans are expected to gain and lose eligibility. Frequently, this churning undermines continuity of care, raises costs, and frustrates those affected. This article explores two proposed programs to mitigate the effects of churn: the Basic Health Program and the Bridge Program. This article evaluates both programs' ability to mitigate the effects of churn, the likely side effects to states' implementing them, and legal and practical obstacles to their implementation. It concludes that the Bridge Program is the better approach. PMID- 25112138 TI - Antitrust and the future of nursing: federal competition policy and the scope of practice. PMID- 25112139 TI - How Medicare Part D, Medicaid, electronic prescribing, and ICD-10 could improve public health (but only if CMS lets them). AB - A simple change to the Medicare and Medicaid outpatient prescription drug billing systems could improve patient safety and the systems' long-term fiscal stability. Including diagnosis codes on prescription drug claims (codes already in use for other billing purposes) would transform the Medicare Part D and Medicaid prescription drug claims databases into powerful public health research tools- ones that could provide much-needed (and, to date, elusive) information on how prescription drugs work in vulnerable patient populations underrepresented in clinical research. Achieving the full potential of this proposal, though, depends upon the federal agency responsible for Medicare and Medicaid, the Centers for Medicare and Medicaid Services (CMS), maintaining its current reimbursement policy, which is perhaps best characterized as one of benign neglect of the statutory standard for coverage. If, instead of continuing coverage for the vast majority of prescription drugs, CMS decided to deny payment for the millions of prescriptions falling short of the statutory standard (and thus avoid spending billions of federal health care dollars), prescribers would find themselves in an ethical dilemma between truth-telling and effectively treating their patients. Due to the systemic incentives for prescribers and pharmacists to miscode diagnoses in order to get CMS to pay for the prescription drugs needed by patients, the decision to treat patients effectively in the short-term under a strict coverage enforcement policy would undermine the potential to more effectively treat vulnerable patients, reduce prescription errors, and properly allocate federal health care dollars in the future. Even in the midst of a financial crisis, or perhaps especially because of our current financial crisis, we cannot afford to sacrifice improved patient safety and better informed long term management of federal health care dollars for a short-term reduction in federal spending on prescription drugs. PMID- 25112141 TI - Mandatory school-based mental health services and the prevention of school violence. PMID- 25112140 TI - Repairing the therapist? Banning reparative therapy for LGB minors. PMID- 25112142 TI - "Death is different": limiting health care for death row inmates. PMID- 25112143 TI - Unwrapped: how the Los Angeles County safer sex in the Adult Film Industry Act's condom mandate hurts performers & violates the First Amendment. PMID- 25112144 TI - Sealing the record: an analysis of jurisdictional variations of juvenile sex offender record sealing laws. PMID- 25112145 TI - Sexual and reproductive health and HIV in border districts affected by migration and poverty in Tanzania. AB - OBJECTIVES: To assess HIV knowledge, attitudes, sexual practices and sexual and reproductive health (SRH) service delivery in border areas of Tanzania, with a view to support the prioritisation of SRH interventions in border areas. METHODS: The target sample comprised randomly selected people living near the border, aged 15 to 49 years. To gather information, we utilised: (i) a standardised questionnaire (n = 86; 42 men and 44 women) previously used in national household surveys conducted by the Tanzanian government; (ii) focus group discussions (ten male groups, n = 47; ten female groups, n = 51); and (iii) semi-structured interviews with service providers (n = 37). RESULTS: The mean number of sexual partners, frequency of multiple concurrent partnerships and engagement in transactional sex were significantly higher in the border community than in the national population. Knowledge about HIV was comparable with that in the general population. Access to SRH services was limited in the border areas. CONCLUSION: Efforts to reduce HIV transmission and to improve SRH in the border areas should focus on gaps in service delivery rather than education and information activities alone. In addition, multi-sectorial efforts spanning the health, social, legal and private sectors addressing gender imbalances and poverty alleviation are imperative for reducing poverty-driven unsafe transactional sex. PMID- 25112146 TI - New approaches in commercial development of artificial oxygen carriers. PMID- 25112148 TI - Interventions to improve adherence to first-line antibiotics in respiratory tract infections. The impact depends on the intensity of the intervention. AB - BACKGROUND: Many interventions aimed at improving the quality of antibiotic prescribing have been investigated, but more knowledge is needed regarding the impact of different intensity interventions. OBJECTIVES: To compare the effect of two interventions, a basic intervention (BI) and intensive intervention (II), aimed to improve the adherence to recommendations on first-line antibiotics in patients with respiratory tract infections (RTIs). METHODS: General practitioners (GPs) from different regions of Spain were offered two different interventions on antibiotic prescribing. They registered all patients with RTIs during 15 days before (2008) and after (2009) the intervention. GPs in Catalonia were exposed to BI including prescriber feedback, clinical guidelines and training sessions focused on appropriate antibiotic prescribing. The other group of GPs was exposed to an II, which besides BI, also included training and access to point-of-care tests in practice. RESULTS: The GPs registered 15 073 RTIs before the intervention and 12 760 RTIs after. The antibiotic prescribing rate reduced from 27.7% to 19.8%. Prescribing of first-choice antibiotics increased after the intervention in both groups. In the group of GPs following the BI, first-line antibiotics accounted for 23.8% of antibiotics before the intervention and 29.4% after (increase 5.6%, 95% confidence interval (CI): 1.2-10%), while in the group of GPs following the II these figures were 26.2% and 48.6% (increase 22.4%, 95% CI: 18.8-26%), respectively. CONCLUSION: Multifaceted interventions targeting GPs can improve adherence to recommendations for first-line antibiotic prescribing in patients with RTI, with intensive interventions that include point-of-care testing being more effective. PMID- 25112147 TI - Perception of high school students on risk for acquiring HIV and utilization of voluntary counseling and testing (VCT) service for HIV in Debre-berhan Town, Ethiopia: a quantitative cross-sectional study. AB - BACKGROUND: Human immunodeficiency virus (HIV) epidemic among youth is largely ignored and remains invisible to both young people themselves and to the society as a whole. Thus, the aim of the study was to assess the extent of perception risk of HIV and utilization of voluntary counseling and testing (VCT) service among high school students at Debre-berhan Town, Amhara Regional State, Ethiopia. METHODS: A cross-sectional study was carried out from November 2010 up to January 2011 among secondary school students at Debre-berhan Town. Perception risk and VCT use were considered as dependant variables. A stratified random sampling technique was used to recruit study participants by taking schools as strata. Semi-structured self-administered questionnaire was used to collect the necessary data. Data was entered and analyzed using SPSS version 17.0. P-value < 0.05 was considered as statistically significant. RESULTS: A total of 339 students were consented to participate in the study and the response rate was 96.3%. The student ages' were ranged from 15 up to 24 years. Among the study participants, 30 (8.8%) had sexual contact and the mean age of first sexual encounter was 16.4 (SD =2.05) years. Of sexually active students, 12 (40%) had sex with different persons within the last 6 months, 13 (43.3%) had ever used condom and 15 (50%) had used VCT service. There was no statistically significant association between risk perception towards HIV infection and ever use of VCT service (AOR (95% CI) = 1.0(0.30, 4.02). CONCLUSIONS: Some students were engaged in risky sexual behavior even though they had heard about HIV/AIDS. The perception of risk for acquisition of HIV infection and utilization of VCT were low. Thus, education on topic of HIV/AIDS through integrating as part of school curriculum and encouraging the existing health institutions to provide youth-friendly sexual counseling services including VCT for HIV are strongly recommended. PMID- 25112149 TI - Exploring precarious employment and women's health within the context of U.S. microenterprise using focus groups. AB - OBJECTIVE: Nursing has been a leader in exploring social determinants of health within the context of U.S. microenterprise and women's health. The purpose of this study was to explore precarious employment within the context of microenterprise and women's health using focus groups with clientele from New Mexico (NM). The specific aims were to identify (1) the health concerns of low income women who utilized resources from Women's Economic Self-Sufficiency Team (WESST), and (2) the meaning of precarious employment in low-income women's lives. DESIGN AND STRATEGY: Fourteen women, ranging in age from 21-65 years, who were affiliated with regional WESST sites around NM participated in focus groups and completed a demographic questionnaire. MEASURES: Focus group data were analyzed using content analysis. The degree of interrater agreement was determined by calculating the Cohen's kappa, percentage agreement, and prevalence adjusted and bias-adjusted kappa (PABAK). RESULTS: Two broad themes emerged from these data: (1) Working for Yourself and (2) Strategies. Although the women identified concerns about participation in microenterprise, flexibility, freedom, and feeling purposeful were motivators to pursue a small business. The kappa statistics on the five transcripts revealed poor inter-rater agreement, yet PABAK, which is a more sophisticated inter-rater reliability index, indicated that inter-rater agreement between the two raters was satisfactory. CONCLUSION: Despite the challenges associated with microenterprise in the US, women found value in working for themselves. PMID- 25112150 TI - Perforated colonic tubulovillous adenoma--a rare presentation. PMID- 25112151 TI - McKittrick-Wheelock syndrome complicated by Enterococcus faecalis endocarditis: a unique combination. PMID- 25112152 TI - Hydrotaea similis Meade (Diptera: Muscidae) newly reported from a human cadaver: a case report and larval morphology. AB - A human cadaver is an attractive breeding habitat for necrophagous insects and for those species that are predators of necrophages. One of the important tasks of forensic entomologists is to provide a reliable list of species associated with decomposing bodies both in the adult and larval stages. We present here a case of a human cadaver discovered in Central Sweden and the insect fauna associated with it. This is the first report of Hydrotaea similis larvae developing in a dead human body. The larvae of H. similis have only recently been studied and, therefore, even if previously they had been collected during forensic casework or experiments, the larvae could not have been properly identified, except if reared to the adult stage. To facilitate future studies and casework, detailed descriptions are provided here of the morphology of third instar larvae of both H. dentipes and H. similis using combined SEM and light microscopy techniques. We describe characters that allow for easy species identification and discrimination of these two forensically important and closely related species. PMID- 25112153 TI - Acute intoxication due to tert-amyl alcohol--a case report. AB - We presented a case of 28 year-old male, who was found in a deep coma complicated with acute respiratory failure because of recreational intoxication with tert amyl alcohol (TAA). The TAA blood level at the admission was 83 MUg/mL determined by gas chromatography-mass spectrometry (GC-MS). In the last few months popularity of TAA among alcohol and drug addicted people in Europe is still growing. The main reasons of these are: self-healing of addiction, low price of this xenobiotic compare to alcohol, and problem to detect this xenobiotic in generally used screening tests. PMID- 25112155 TI - Association between transforming growth factor-beta1gene-509C/T polymorphism and susceptibility of IgA nephropathy: a meta-analysis. AB - A role for transforming growth factor-beta1gene has been suggested in the etiology of IgA nephropathy. However, results have been inconsistent. In this study, a meta-analysis was performed to further clarify the association between transforming growth factor-beta1-509C/T gene polymorphism and the susceptibility of IgA nephropathy. PubMed, EMBASE, Web of Science, CNKI, WanFang, and VIP Data were searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals were calculated using a fixed-effects model or random-effects model. A total of eight publications involving 1355 IgA nephropathy patients and 1464 controls met the inclusion and were analyzed. The pooled ORs for the association between TGF-beta1gene-509C/T polymorphism and IgA nephropathy risk were not statistically significant under all genetic models (for CT+TT vs. CC: OR = 1.09; 95% CI = 0.92-1.29, p = 0.490; for TT vs. CT+CC: OR = 1.14; 95% CI = 0.94-1.38, p = 0.081; for CC vs. TT: OR = 0.87; 95% CI = 0.69-1.08, p = 0.195; for C allele vs. T allele: OR = 0.92; 95% CI = 0.83-1.03, p = 0.149). In the stratified analysis by ethnicity, results also showed no significant association between TGF beta1 gene-509C/T polymorphism and IgA nephropathy risk in both European and Asian populations. This meta-analysis does not support the hypothesis that TGF beta1 gene-509C/T polymorphism is a risk factor for the development of IgA nephropathy. PMID- 25112154 TI - Prolonged ingestion of ovalbumin diet by sensitized mice improves the metabolic consequences induced by experimental food allergy. AB - The prevalence of food allergy is rising in the western world. Allergen restriction is the chosen treatment in this condition, but continuous ingestion of the antigen has shown positive results in clinical trials. In a previous study, we have shown several allergic and metabolic alterations after 7 days of ovalbumin (OVA) ingestion by sensitized mice. The aim of this study was to investigate whether prolonged ingestion of antigen by sensitized mice would reverse the metabolic consequences caused by experimental food allergy. For this, allergic and metabolic parameters were analysed after prolonged ingestion of an OVA diet by OVA-sensitized mice. As shown previously, after 7 days of OVA consumption, sensitized mice showed increased serum levels of anti-OVA immunoglobulin (Ig)E and IgG1, aversion to the antigen ingestion, marked body and adipose tissue weight loss, followed by adipose tissue inflammation and decreased serum levels of adipokines, glucose and triglycerides. However, after 14 days of oral challenge, sensitized mice showed an anti-OVA IgE level similar to the mice that were only sensitized, but the specific IgG1 did not change. With this prolonged ingestion of OVA, sensitized mice were protected from OVA-induced anaphylaxis when the antigen was given systemically at a dose of 2 mg/animal. Moreover, various parameters analysed were significantly ameliorated, including adipose tissue inflammation, body and adipose tissue loss, as well as serum levels of adipokines and triglycerides. Therefore, our data suggest that prolonged ingestion of OVA by sensitized mice results in an improvement of the metabolic consequences caused by experimental food allergy. PMID- 25112156 TI - Hydrogenation of amides catalyzed by a combined catalytic system of a Ru complex with a zinc salt. AB - Addition of catalytic amounts of zinc salts facilitated the hydrogenation of amides catalyzed by a ruthenium complex bearing 2-(diphenylphosphino)ethanamine (L1). The combined catalytic system of the ruthenium complex [RuCl2(L1)2] with a zinc salt such as Zn(OCOCF3)2 mediated hydrogenation of various amides under mild conditions to afford the corresponding primary alcohols. PMID- 25112157 TI - Affinity purified anti-citrullinated protein/peptide antibodies target antigens expressed in the rheumatoid joint. AB - INTRODUCTION: A major subset of patients with rheumatoid arthritis (RA) is characterized by the presence of circulating autoantibodies directed to citrullinated proteins/peptides (ACPAs). These autoantibodies, which are commonly detected by using an enzyme-linked immunosorbent assay (ELISA) based on synthetic cyclic citrullinated peptides (CCPs), predict clinical onset and a destructive disease course. In the present study, we have used plasma and synovial fluids from patients with RA, for the affinity purification and characterization of anti CCP2 reactive antibodies, with an aim to generate molecular tools that can be used in vitro and in vivo for future investigations into the pathobiology of the ACPA response. Specifically, this study aims to demonstrate that the surrogate marker CCP2 can capture ACPAs that bind to autoantigens expressed in vivo in the major inflammatory lesions of RA (that is, in the rheumatoid joint). METHODS: Plasma (n = 16) and synovial fluid (n = 26) samples were collected from RA patients with anti-CCP2 IgG levels of above 300 AU/mL. Total IgG was isolated on Protein G columns and subsequently applied to CCP2 affinity columns. Purified anti-CCP2 IgG was analyzed for reactivity and specificity by using the CCPlus(r) ELISA, in-house peptide ELISAs, Western blot, and immunohisto /immunocytochemistry. RESULTS: Approximately 2% of the total IgG pool in both plasma and synovial fluid was CCP2-reactive. Purified anti-CCP2 reactive antibodies from different patients showed differences in binding to CCP2 and differences in binding to citrullinated peptides from alpha-enolase, vimentin, fibrinogen, and collagen type II, illustrating different ACPA fine-specificity profiles. Furthermore, the purified ACPA bound not only in vitro citrullinated proteins but, more importantly, in vivo-generated epitopes on synovial fluid cells and synovial tissues from patients with RA. CONCLUSIONS: We have isolated ACPAs from plasma and synovial fluid and demonstrated that the CCP2 peptides, frequently used in diagnostic ELISAs, de facto act as surrogate antigens for at least four different, well-characterized, largely non-cross-reactive, ACPA fine specificities. Moreover, we have determined the concentration and proportion of CCP2-reactive IgG molecules in rheumatoid plasma and synovial fluid, and we have shown that the purified ACPAs can be used to detect both in vitro- and in vivo generated citrullinated epitopes by various techniques. We anticipate that these antibodies will provide us with new opportunities to investigate the potential pathogenic effects of human ACPAs. PMID- 25112159 TI - Relation between jumping to conclusions and cognitive functioning in people with schizophrenia in contrast with healthy participants. AB - 'Jumping to conclusions' (JTC) is a reasoning bias consisting of a tendency to take a decision without having enough information about an event. It has been related to the presence of delusions. The aim of the present study was to assess the relationship between three tasks differing in complexity and concept which assess JTC and cognitive functioning in a sample of people with schizophrenia and healthy participants. We also assessed which cognitive variables, after controlling for psychotic symptoms, explained the presence of JTC in each sample. A total of 43 patients with schizophrenia and 57 healthy participants were assessed with a cognition battery including executive function, verbal memory, and IQ. JTC was assessed with three tasks (probability of 85:15; 60:40, and 60:40 with emotional component). Patients were also assessed on psychotic and affective symptoms and the healthy participants on proneness to hallucinations and delusion. The present study demonstrates a clear relationship between JTC and cognitive functioning, especially in working memory, verbal memory, and cognitive processing speed in people with schizophrenia and in healthy participants. However no relationship was found in the emotional task of JTC. Hallucinations (in people with schizophrenia) and proneness to hallucinations (in the healthy participants) are related to JTC. Our results suggest that diverse psychological interventions such as cognitive remediation, cognitive behavioral therapy and meta-cognitive training might contribute to reducing JTC bias. PMID- 25112158 TI - Disease and drug effects on internally-generated and externally-elicited responses in first episode schizophrenia and psychotic bipolar disorder. AB - Neurocognitive deficits are associated with most psychotic disorders, but may differ across diagnosis and by treatment status. This ambiguity is partly addressed in longitudinal pre/post treatment studies with first episode patients. Antipsychotic-naive first-episode schizophrenia patients have shown intact performance on a predictive saccade task that assesses simple motor learning, spatial abilities, and response planning. After antipsychotic treatment, however, schizophrenia patients performing this task show a selective impairment in the accuracy of anticipatory responses, generated from learned internal representations of the task stimulus. This finding is in line with other observations of antipsychotic medication effects on frontostriatal systems, particularly dorsolateral prefrontal cortex. We sought to replicate this provocative finding with an independent sample of antipsychotic-naive first episode schizophrenia patients and extend it by including a group of patients with first episode bipolar disorder with psychosis (BDP). Matched healthy controls were also studied in parallel. Schizophrenia patients demonstrated intact performance pretreatment followed by impairment post-treatment for accuracy of anticipatory responses, and worse accuracy was associated with higher antipsychotic dose. BDP patients displayed saccade accuracy deficits before and after treatment and had no correlation of performance and antipsychotic dose. The findings suggest different neural alterations early in the course of each psychotic disorder, and different vulnerabilities to antipsychotic treatment effects between schizophrenia and BDP. PMID- 25112160 TI - The Arcuate Fasciculus in auditory-verbal hallucinations: a meta-analysis of diffusion-tensor-imaging studies. AB - Auditory-verbal hallucinations (AVHs) are associated with an impaired connectivity of large-scale networks. To examine the relationship between white matter integrity and AVHs, we conducted a meta-analysis of diffusion-tensor imaging studies that compared patients with schizophrenia and AVHs with matched healthy controls (HCs). Five studies were retained gathering 256 DTI data points, divided into AVHs (n=106) and HCs (n=150). The meta-analysis demonstrated a reduced fractional anisotropy in the left Arcuate Fasciculus (AF) of hallucinators (hg= -0.42; CI[-0.69,-0.16]; p<10(-3)). The current meta-analysis confirmed disruptions of white matter integrity in the left AF bundle of schizophrenia patients with AVHs. PMID- 25112162 TI - Copper(II) coordination polymers with azide and bipyridine-based zwitterionic carboxylate ligands: structures and magnetism. AB - Two novel Cu(II) coordination polymers, [Cu4O(L(1))4(N3)2]n(ClO4)4n.3nH2O (1) and [Cu7(L(2))2(N3)14]n (2), have been synthesized from two zwitterionic carboxylate ligands, 1-carboxylatomethyl-4,4'-bipyridinium (L(1)) and 1-carboxylatomethyl 4,4'-dimethylenedipyridinium (L(2)). Compound 1 exhibits interpenetrated 3D diamond networks in which the unusual MU4-O-centred tetrahedral Cu4 clusters with peripheral 1,1-N3 and COO bridges are cross-linked by 4,4'-dipyridinium-1 methylene spacers. In compound 2, pentanuclear and dinuclear units with double azide bridges are linked into a unique 2D layer by MU3-1,1,3-N3, (1,1-N3)(COO) and the organic backbone of the zwitterionic ligand. Magnetic studies reveal that compound 1 exhibits ferromagnetic coupling through (MU4-O)(1,1-N3) and antiferromagnetic coupling through the MU4-O-only and (MU4-O)(COO)2 pathways. Compound 2 exhibits ferromagnetic coupling within the (1,1-N3)2 bridged polynuclear units and weak antiferromagnetic coupling through MU3-1,1,3-N3, and (1,1-N3)(COO) between the units. PMID- 25112161 TI - The nature and timing of social deficits in child and adolescent offspring of parents with schizophrenia: preliminary evidence for precursors of negative symptoms? AB - Children with social dysfunction and a first-degree relative with schizophrenia are at elevated risk for schizophrenia; however, the nature of this dysfunction is unclear. It was hypothesized that familial high-risk (HR) children and adolescents (n=17) would have social skill deficits relative to healthy controls (HC; n=35). HR participants had a bimodal distribution of social skill scores (47% excellent; 53% poor). HR participants had worse social skills, assertion and empathy scores, suggesting possible developmental precursors to the social amotivation domain of negative symptoms. Characterizing HR children's social deficits could assist identification of those at risk for schizophrenia. PMID- 25112163 TI - Gas sensing of SnO2 nanocrystals revisited: developing ultra-sensitive sensors for detecting the H2S leakage of biogas. AB - As a typical mode of energy from waste, biogas technology is of great interest to researchers. To detect the trace H2S released from biogas, we herein demonstrate a high-performance sensor based on highly H2S-sensitive SnO2 nanocrystals, which have been selectively prepared by solvothermal methods using benzimidazole as a mineralization agent. The sensitivity of as-obtained SnO2 sensor towards 5 ppm H2S can reach up to 357. Such a technique based on SnO2 nanocrystals opens up a promising avenue for future practical applications in real-time monitoring a trace of H2S from the leakage of biogas. PMID- 25112164 TI - Epidemiology of nasopharyngeal colonization by S. pneumoniae in Indian infants in the first 2 years of life. AB - BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive disease in developing countries like India. Although the 13 valent pneumococcal vaccine has already been introduced in the country, there is very little epidemiological data regarding S. pneumoniae colonization and antibiotic susceptibility in Indian infants. METHODS: We studied serogroup/serotype (SGT) distribution and antibiotic susceptibility pattern of S. pneumoniae in unvaccinated Indian infants by performing monthly nasopharyngeal swabbing of a birth cohort for 2 years. RESULTS: Colonization began soon after birth and was complete in the first year of life in the majority of those colonized. Carriage rates increased during winter (p<0.01) and in those with upper respiratory infection (URI) (p<0.01). The most frequently (76.1%) isolated SGT were 19, 6, 15, 23, 9, 35 and 10. Vaccine SGT accounted for 60.5% of all colonizers. Antibiotic resistance was maximum for cotrimoxazole (94.3%) and least for erythromycin (11.2%) with no penicillin resistance. Ten of the commonest SGT which cause invasive disease among Indian infants comprised 46.9% of the colonizers. Serogroups 1, 5, 45 and 12 which cause invasive disease in under-fives were not seen in this birth cohort in the first year. CONCLUSIONS: S. pneumoniae colonization in Indian infants commences soon after birth and chiefly occurs in the first year of life. The 13 valent vaccine may protect against a little less than half the commonly seen invasive SGT of S. pneumoniae. PMID- 25112165 TI - Speech outcomes at age 5 and 10 years in unilateral cleft lip and palate after one-stage palatal repair with minimal incision technique - a longitudinal perspective. AB - OBJECTIVES: To investigate speech outcomes in 5- and 10-year-old children with unilateral cleft lip and palate (UCLP) treated according to minimal incision technique (MIT) - a one-stage palatal method. METHODS: A retrospective, longitudinal cohort study of a consecutive series of 69 patients born with UCLP, treated with MIT (mean age 13 months) was included. Forty-two children (43%) received a velopharyngeal flap; 12 before 5 years and another 18 before 10 years of age. Cleft speech variables were rated from standardized audio recordings at 5 and 10 years of age, independently by three experienced, external speech-language pathologists, blinded to the material. The prevalences of cleft speech characteristics were determined, and inter- and intra-rater agreement calculated. RESULTS: More than mild hypernasality, weak pressure consonants and perceived incompetent velopharyngeal function were present in 19-22% of the children at 5 years, but improved to less than 5% at 10 years. However, audible nasal air leakage, prevalent in 23% at 5 years, did not improve by age 10. Thirty percent had frequent or almost always persistent compensatory articulation at 5 years, and 6% at age 10. The general impression of speech improved markedly, from 57% giving a normal impression at 5 years to 89% at 10 years. A high prevalence of distorted/s/was found at both 5 and 10 years of age. CONCLUSIONS: A high occurrence of speech deviances at 5 years of age after MIT was markedly reduced at 10 years in this study of children with unilateral cleft lip and palate. The high pharyngeal flap rate presumably accounted for the positive speech development. PMID- 25112166 TI - Pseudohypacusis in children: circumstances and diagnostic strategy. AB - OBJECTIVES: The study attempts to specify the circumstances under which we should pay attention to children's pseudohypacusis. It evaluates the methods used to detect such cases and to determine hearing thresholds, according to the uni-or bilateralism of hearing loss. The study finally deals with the future of children diagnosed with pseudohypacusis. METHODS: The study was retrospective from January 1993 to November 2011 and prospective from December 2011 to April 2012. We included all the children between 3 and 16 years who were diagnosed with pseudohypacusis. We observed the reasons for them to consult, whether they had already been tested or had treatment, and what kind of hearing loss they displayed. All children were tested using standard pure tone audiometry and speech audiometry. Depending on the first results, other tests were conducted. They included transient evoked otoacoustic emissions (TEOEs), auditory brainstem responses (ABR) and auditory steady state responses. Families were finally contacted by phone over April 2012 in order to let them know about their child's results. RESULTS: Fifty-four children were included: 19 boys and 35 girls, with an average age of 10 year-old (+/-3). The simulated hearing loss (HL) was bilateral (36), unilateral (18), of perception (37), moderate HL (33), cophosis (5). Fifteen cases were linked to a family or personal history of hearing loss, while 27 cases were due to important events like adoption, abuse, verbal aggression, school problems. Before diagnosing a pseudohypacusis, 13 children had had imaging studies, 3 had been treated with corticosteroids, and 5 had hearing aids. Most of the time the presence of pseudohypacusis was suspected a discrepancy between speech reception and air-conduction pure tone thresholds, as shown by the medical test (answer on whispered voice). The diagnosis was confirmed by ABR or TEOEs, except in cases where clinic was obvious. Then family's patient and patient were reassured and informed. An audiological follow up during either 6 months or 1 year was proposed, as well as a psychological consultation. CONCLUSION: Complementary examinations have to be performed to rule out a pseudohypacusis case before suggesting an invasive or expensive treatment (surgery or hearing aids) of children. PMID- 25112167 TI - A test protocol for assessing the hearing status of students with special needs. AB - OBJECTIVES: Individuals with disabilities are often reported to have a high prevalence of undetected hearing disorders/loss, but there is no standardized hearing test protocol for this population. The purposes of this study were (1) to examine the hearing status of students with special needs in Taiwan, and (2) to investigate the use of an on-site hearing test protocol that would adequately detect hearing problems in this population and reduce unnecessary referrals for off-site follow-up services. METHODS: A total of 238 students enrolled in two schools for special education and one habilitation center participated in the study. Most students had intellectual disabilities and some also had additional syndromes or disorders. A hearing screening protocol including otoscopy, tympanometry, and distortion product otoacoustic emissions was administered to examine students' outer, middle, and inner ear functions, respectively. Pure tone tests were then administered as an on-site follow-up for those who failed or could not be tested using the screening protocol. RESULTS: Only 32.4% of students passed. When administered alone, the referral rate of otoscopy, tympanometry, and otoacoustic emissions were 38.7%, 46.0%, and 48.5%, respectively. The integration of these subtests revealed 52.1% of students needed follow-up services, 11.8% could not be tested, 2.5% had documented hearing loss, and 1.3% needed to be monitored because of negative middle ear pressure. The inclusion of pure tone audiometry increased the passing rate by 9.9% and provided information on hearing sensitivity for an additional 8.6% of students. CONCLUSION: Hearing assessments and regular hearing screening should be provided as an integral part of health care services for individuals with special needs because of high occurrences of excessive cerumen, middle ear dysfunction, and sensorineural hearing loss. The training of care-givers and teachers of students with special needs is encouraged so that they can help identify hearing problems and reduce the negative impact of hearing disorders and hearing loss. The screening protocol needs to include subtests that examine the status of different parts of their auditory system. The addition of pure tone audiometry as an on-site follow-up tool reduced the rate of off-site referrals and provided more information on hearing sensitivity. PMID- 25112169 TI - The roles of the Q (q) wave in lead I and QRS frontal axis for diagnosing loss of left ventricular capture during cardiac resynchronization therapy. AB - INTRODUCTION: Loss of left ventricular (LV) capture may lead to deterioration of heart failure in patients with cardiac resynchronization therapy (CRT). Recognition of loss of LV capture in time is important in clinical practice. METHODS AND RESULTS: A total of 422 electrocardiograms were acquired and analyzed from 53 CRT patients at 8 different pacing settings (LV only, right ventricle [RV] only, biventricular [BV] pacing with LV preactivation of 60, 40, 20, and 0 milliseconds and RV preactivation of 20 and 40 milliseconds). A modified Ammann algorithm by adding a third step-presence of Q (q, or QS) wave-to the original 2 step Ammann algorithm and a QRS axis shift method were devised to identify the loss of LV capture. The accuracy of modified Ammann algorithm was significantly higher than that of Ammann algorithm (78.9% vs. 69.1%, P < 0.001). The accuracy of the axis shift method was 66.4%, which was significantly lower than the modified Ammann algorithm (P < 0.001) and similar to the original one (P = 0.412). However, in the ECGs with QRS axis shift, 96.8% were correctly classified. LV preactivation or simultaneous BV activation and LV lead positioned in nonposterior or noninferior wall could elevate the accuracies of the modified Ammann algorithm and the QRS axis shift method. CONCLUSIONS: The accuracy of the modified Ammann algorithm is greatly improved. The QRS axis shift method can help diagnose LV capture. The LV preactivation, or simultaneous BV activation and LV lead positioned in nonposterior or noninferior wall can increase the diagnostic power of the modified Ammann algorithm and QRS axis shift method. PMID- 25112168 TI - De novo transcriptome sequencing and digital gene expression analysis predict biosynthetic pathway of rhynchophylline and isorhynchophylline from Uncaria rhynchophylla, a non-model plant with potent anti-alzheimer's properties. AB - BACKGROUND: The major medicinal alkaloids isolated from Uncaria rhynchophylla (gouteng in chinese) capsules are rhynchophylline (RIN) and isorhynchophylline (IRN). Extracts containing these terpene indole alkaloids (TIAs) can inhibit the formation and destabilize preformed fibrils of amyloid beta protein (a pathological marker of Alzheimer's disease), and have been shown to improve the cognitive function of mice with Alzheimer-like symptoms. The biosynthetic pathways of RIN and IRN are largely unknown. RESULTS: In this study, RNA sequencing of pooled Uncaria capsules RNA samples taken at three developmental stages that accumulate different amount of RIN and IRN was performed. More than 50 million high-quality reads from a cDNA library were generated and de novo assembled. Sequences for all of the known enzymes involved in TIAs synthesis were identified. Additionally, 193 cytochrome P450 (CYP450), 280 methyltransferase and 144 isomerase genes were identified, that are potential candidates for enzymes involved in RIN and IRN synthesis. Digital gene expression profile (DGE) analysis was performed on the three capsule developmental stages, and based on genes possessing expression profiles consistent with RIN and IRN levels; four CYP450s, three methyltransferases and three isomerases were identified as the candidates most likely to be involved in the later steps of RIN and IRN biosynthesis. CONCLUSION: A combination of de novo transcriptome assembly and DGE analysis was shown to be a powerful method for identifying genes encoding enzymes potentially involved in the biosynthesis of important secondary metabolites in a non-model plant. The transcriptome data from this study provides an important resource for understanding the formation of major bioactive constituents in the capsule extract from Uncaria, and provides information that may aid in metabolic engineering to increase yields of these important alkaloids. PMID- 25112170 TI - Room-temperature sensor based on surface-enhanced Raman spectroscopy. AB - As reported in the literature, several factors, such as scattering cross sections, polarisability and wavelength suitability, contribute to increased SERS enhancement. In general, the advantage of surface-enhanced Raman scattering (SERS)-active Ag nanoparticles (NPs) is their higher SERS enhancement over Au NPs because the molar extinction coefficient of the Ag NPs is the highest of its kind among metals. Nevertheless, the corresponding SERS-active hot spots on Au are of inherently greater stability than on Ag. In this work, innovative temperature sensors based on SERS-active Au and Ag substrates prepared by sonoelectrochemical deposition-dissolution cycles (SEDDCs) are first reported. The SERS intensity of the model probe molecules of Rhodamine 6G (R6G) adsorbed on a SERS-active Ag substrate is monotonically increased from 25 to 50 degrees C. Moreover, this temperature-dependent intensity is linear with a slope of ca. 430 cps per degrees C between 25 to 45 degrees C. In addition, the reversibility and reusability of the developed temperature sensors are evaluated after the R6G adsorbed sensors are alternately exposed to the temperatures of 25 and 45 degrees C in a sealed chamber. After every five cycles, the SERS spectra of treated substrates were recorded and compared with those of the as-prepared substrates. Experimental results indicate that SERS enhancement capability is mostly reversible based on 90% intensity of the Raman signal being maintained for the SERS-active Au substrate after 25 cycles (only 15 cycles for the Ag substrate). PMID- 25112172 TI - Steep drop in hematocrit of sheep undergoing sedation with acepromazine-diazepam and epidural injections of ketamine, ketamine-morphine or ketamine-xylazine. PMID- 25112171 TI - Asymmetric transverse control of maxillary dentition with two midpalatal orthodontic miniscrews. AB - There have been several orthodontic modalities for maxillary transverse control with most addressing symmetric control. The asymmetric transverse control of maxillary dentition is challenging to orthodontists due to the lack of certain modalities and possible dental side effects. Skeletal anchorages provide biomechanics without orthodontic side effects, but reports of their utilization for transverse control of maxillary dentition are scarce. The purpose of this article is to introduce a novel method utilizing two midpalatal orthodontic miniscrews and a connecting wire system for the asymmetric transverse control of maxillary dentition. Records of two patients consecutively treated with this system are reported, and the related biomechanical considerations are presented. PMID- 25112173 TI - Clinical utility and validity of minoxidil response testing in androgenetic alopecia. AB - Clinical response to 5% topical minoxidil for the treatment of androgenetic alopecia (AGA) is typically observed after 3-6 months. Approximately 40% of patients will regrow hair. Given the prolonged treatment time required to elicit a response, a diagnostic test for ruling out nonresponders would have significant clinical utility. Two studies have previously reported that sulfotransferase enzyme activity in plucked hair follicles predicts a patient's response to topical minoxidil therapy. The aim of this study was to assess the clinical utility and validity of minoxidil response testing. In this communication, the present authors conducted an analysis of completed and ongoing studies of minoxidil response testing. The analysis confirmed the clinical utility of a sulfotransferase enzyme test in successfully ruling out 95.9% of nonresponders to topical minoxidil for the treatment of AGA. PMID- 25112174 TI - Awareness of surgical costs: a multicenter cross-sectional survey. AB - BACKGROUND: Resource scarcity continues to be an important problem in modern surgical practice. Studies in North America and Europe have found that medical professionals have limited understanding of the costs of medical care. No cost awareness studies have been undertaken in Australasia or specifically focusing on the surgical team. This study determined the cost of a range of commonly used diagnostic tests, procedures, and hospital resources associated with care of the surgical patient. The surgical teams' awareness of these costs was then assessed in a multicenter cross-sectional survey. METHODS: In total, 14 general surgical consultants, 14 registrars, and 25 house officers working in three New Zealand hospitals were asked to estimate the costs of 14 items commonly associated with patient care. Cost estimations were considered correct if within 25% plus or minus of the actual cost. Accuracy was assessed by calculating the median, mean, and absolute percentage discrepancy. RESULTS: A total of 57 surveys were completed. Of which, four were incomplete and were not included in the analysis. Cost awareness was generally poor, and members of the surgical team were rarely able to estimate the costs to within 25%. The mean absolute percentage error was 0.87 (95% CI: 0.58-1.18) and underestimates were most common. There was no significant difference in estimate accuracy between consultants, registrars, or house officers, or between consultants working in both public/private practice compared with those working in public practice alone. CONCLUSION: There is poor awareness of surgical costs among consultant surgeons, registrars, and junior physicians working in Australasia. PMID- 25112176 TI - The paradox of atrial fibrillation in African Americans. AB - The reported lower prevalence and incidence of atrial fibrillation (AF) despite the higher prevalence of AF risk factors in African Americans compared to Caucasian whites has been referred to as the paradox of AF in African Americans. In this report we highlight this paradox and address potential explanations using data from several US populations studies. These possible explanations include limited methodology to detect AF patterns that are harder to detect (e.g. paroxysmal/intermittent AF or atrial flutter) coupled with the possibility of African Americans having more of these patterns, differential access to health care with African Americans having less access and subsequently less detected AF, survival bias with Caucasian whites living longer and subsequently having more AF, and finally differential impact of AF risk factors with Caucasian whites being more affected or African Americans less affected by AF risk factors whether this is genetically determined or via other unknown predispositions. PMID- 25112177 TI - Antagonism of D1/D5 receptors prevents long-term depression (LTD) and learning facilitated LTD at the perforant path-dentate gyrus synapse in freely behaving rats. AB - Hippocampal synaptic plasticity, in the form of long-term potentiation (LTP) and long-term depression (LTD), enables spatial memory formation, whereby LTP and LTD are likely to contribute different elements to the resulting spatial representation. Dopamine, released from the ventral tegmental area particularly under conditions of reward, acts on the hippocampus, and may specifically influence the encoding of information into long-term memory. The dentate gyrus (DG), as the "gateway" to the hippocampus is likely to play an important role in this process. D1/D5 dopamine receptors are importantly involved in the regulation of synaptic plasticity thresholds in the CA1 region of the hippocampus and determine the direction of change in synaptic strength that occurs during novel spatial learning. Here, we explored whether D1/D5-receptors influence LTD that is induced in the DG following patterned afferent stimulation of the perforant path of freely behaving adult rats, or influence LTD that occurs in association with spatial learning. We found that LTD that is induced by afferent stimulation, and LTD that is facilitated by learning about novel landmark configurations, were both prevented by D1/D5-receptor antagonism, whereas agonist activation of the D1/D5-receptor had no effect on basal tonus or short-term depression. Other studies have reported that in the DG, D1/D5-receptor agonism or antagonism do not affect LTP, but agonism prevents depotentiation. These findings suggest that the dopaminergic system, acting via D1/D5-receptors, influences information gating by the DG and modulates the direction of change in synaptic strength that underlies information storage in this hippocampal substructure. Information encoded by robust forms of LTD is especially dependent on D1/D5-receptor activation. Thus, dopamine acting on D1/D5-receptors is likely to support specific experience dependent encoding, and may influence the content of hippocampal representations of experience. PMID- 25112175 TI - Tryptophan supplementation and postoperative delirium--a randomized controlled trial. AB - OBJECTIVES: To determine whether the postoperative administration of tryptophan would be beneficial for elderly adults undergoing surgery who are at risk of developing postoperative delirium. DESIGN: Randomized, double-blind, placebo controlled trial. SETTING: Denver Veterans Affairs Medical Center. PARTICIPANTS: Individuals aged 60 and older undergoing major elective operations requiring a postoperative intensive care unit (ICU) admission (n = 325). INTERVENTION: L tryptophan, 1 g orally three times a day or placebo was started after surgery and continued for up to 3 days postoperatively. MEASUREMENTS: Delirium and its motor subtypes were measured using the Confusion Assessment Method-Intensive Care Unit (CAM-ICU) and the Richmond Agitation and Sedation Scale. The primary outcome for between-group comparison was the incidence of excitatory (mixed and hyperactive) postoperative delirium. The secondary outcomes for comparison were the incidence and duration of overall postoperative delirium. RESULTS: The overall incidence of postoperative delirium was 39% (95% confidence interval = 34-44%) (n = 116). Seventeen percent of participants in the tryptophan group and 9% in the placebo group had excitatory delirium (P = .18), and the duration of excitatory delirium was 3.3 +/- 1.7 days for tryptophan and 3.1 +/- 1.9 days for placebo (P = .74). Forty percent of participants in the tryptophan group and 37% in the placebo group had overall delirium (P = .60), and the duration of overall delirium was 2.9 +/- 1.8 days for tryptophan and 2.4 +/- 1.6 days for placebo (P = .17). CONCLUSION: Postoperative tryptophan supplementation in older adults undergoing major elective operations requiring postoperative ICU admission did not reduce the incidence or duration of postoperative excitatory delirium or overall delirium. PMID- 25112178 TI - [Treatment of giant acoustic neuromas]. AB - INTRODUCTION AND OBJECTIVES: To analyze the treatment modality and outcome of a series of patients with giant acoustic neuromas, a particular type of tumour characterised by their size (extracanalicular diameter of 4cm or more) and high morbidity and mortality. MATERIALS AND METHODS: This was a retrospective unicentre study of patients with acoustic neuromas treated in a period of 12 years. In our institutional series of 108 acoustic neuromas operated on during that period, we found 13 (12%) cases of giant acoustic neuromas. We reviewed the available data of these cases, including presentation and several clinical, anatomical, and microsurgical aspects. RESULTS: All patients were operated on by the same neurosurgeon and senior author (EU) using the suboccipital retrosigmoid approach and complete microsurgical removal was achieved in 10 cases. In one case, near total removal was deliberately performed, in another case a CSF shunt was placed as the sole treatment measure, and in the remaining case no direct treatment was given. One patient died in the immediate postoperative period. One year after surgery, 4 patients showed facial nerve function of iii or more in the House-Brackman scale. CONCLUSIONS: The 4 most important prognostic characteristics of giant acoustic neuromas are size, adhesion to surrounding structures, consistency and vascularity. Only the first of these is evident in neuroimaging. Giant acoustic neuromas are characterised by high morbidity at presentation as well as after treatment. Nevertheless, the objective of complete microsurgical removal with preservation of cranial nerve function is attainable in some cases through the suboccipital retrosigmoid approach. PMID- 25112179 TI - Vitamin D deficiency in minority populations. AB - OBJECTIVE: Black and Hispanic individuals synthesize less vitamin D per unit of sun exposure than white individuals. The relationship between UV radiation and vitamin D insufficiency in minorities has not been well explored. DESIGN: Prospective cohort study. SETTING: Using the National Health and Nutrition Examination Survey, we obtained serum vitamin D levels for non-Hispanic Whites, Hispanics and non-Hispanic Blacks aged >=18 years from 2000-2006. We linked these data with the average monthly solar UV index by census tract and data on sun exposure, vitamin D supplementation, health and demographics. We used multivariable regression analyses to assess vitamin D deficiency (<15 ng/ml) and insufficiency (<20 ng/ml) in January (when the UV index was lowest) by race/ethnicity and geography. SUBJECTS: Adults (n 14,319) aged >=18 years. RESULTS: A 1-point increase in the UV index was associated with a 0.51 ng/ml increase in vitamin D (95% CI 0.35, 0.67 ng/ml; P<0.001). Non-Hispanic Black race and Hispanic ethnicity were associated with a 7.47 and 3.41 ng/ml decrease in vitamin D, respectively (both P<0.001). In January, an estimated 65.4% of non Hispanic Blacks were deficient in vitamin D, compared with 28.9% of Hispanics and 14.0% of non-Hispanic Whites. An estimated 84.2% of non-Hispanic Blacks were insufficient in vitamin D v. 56.3% of Hispanics and 34.8% of non-Hispanic Whites. More non-Hispanic Blacks were estimated to be deficient in vitamin D in January in the highest UV index quartile than were non-Hispanic Whites in the lowest UV index quartile (60.2% v. 25.7%). CONCLUSIONS: Wintertime vitamin D insufficiency is pervasive among minority populations, and not uncommon among non-Hispanic Whites. PMID- 25112181 TI - Microfluidic geometric metering-based multi-reagent mixture generator for robust live cell screening array. AB - Microfluidic live cell arrays with integrated concentration gradient or mixture generators have been utilized in screening cellular responses to various biomolecular cues. Microfluidic network-based gradient generators that can create concentration gradients by repeatedly splitting and mixing different solutions using networks of serpentine channels are commonly used. However, in this method the generation of concentration gradients relies on the continuous flow of sample solutions at optimized flow rates, which poses challenges in maintaining the pressure and flow stability throughout the entire assay period. Here we present a microfluidic live cell screening array with an on-demand multi-reagent mixture generator where the mixing ratios, thus generated concentrations, are hard-wired into the chip itself through a geometric metering method. This platform showed significantly improved robustness and repeatability in generating concentration gradients of fluorescent dyes (average coefficient of variance C.V. = 9 %) compared to the conventional network-based gradient generators (average C.V. = 21 %). In studying the concentration dependent effects of the environmental toxicant 3-methylcholanthrene (3MC) on the activation of cytochrome P450 1A1 (Cyp 1A1) enzyme in H4IIE rat hepatoma cells, statistical variation of the Cyp 1A1 response was significantly lower (C.V. = 5 %) when using the developed mixture generator compared to that using the conventional gradient generator (C.V. = 12 %). Reduction in reagent consumption by 12-times was also achieved. This robust, accurate, and scalable multi-reagent mixture generator integrated with a cell culture array as a live cell assay platform can be readily implemented into various screening applications where repeatability, robustness, and low reagent consumptions over long periods of assay time are of importance. PMID- 25112180 TI - The important ergot alkaloid intermediate chanoclavine-I produced in the yeast Saccharomyces cerevisiae by the combined action of EasC and EasE from Aspergillus japonicus. AB - BACKGROUND: Ergot alkaloids are a group of highly bioactive molecules produced by a number of filamentous fungi. These compounds have been intensely studied for decades, mainly due to their deleterious effects in contaminated food and feeds, but also for their beneficial pharmaceutical and agricultural applications. Biosynthesis of ergot alkaloids goes via the common intermediate chanoclavine-I, and studies of the key enzymes, EasE and EasC, involved in chanoclavine-I formation, have relied on gene complementation in fungi, whereas further characterization has been hampered by difficulties of poor EasE protein expression. In order to facilitate the study of ergot alkaloids, and eventually move towards commercial production, the early steps of the biosynthetic pathway were reconstituted in the unicellular yeast Saccharomyces cerevisiae. RESULTS: The genomic sequence from an ergot alkaloid producer, Aspergillus japonicus, was used to predict the protein encoding sequences of the early ergot alkaloid pathway genes. These were cloned and expressed in yeast, resulting in de novo production of the common intermediate chanoclavine-I. This allowed further characterization of EasE and EasC, and we were able to demonstrate how the N terminal ER targeting signal of EasE is crucial for activity in yeast. A putative, peroxisomal targeting signal found in EasC was shown to be nonessential. Overexpression of host genes pdi1 or ero1, associated with disulphide bond formation and the ER protein folding machinery, was shown to increase chanoclavine-I production in yeast. This was also the case when overexpressing host fad1, known to be involved in co-factor generation. CONCLUSIONS: A thorough understanding of the enzymatic steps involved in ergot alkaloid formation is essential for commercial production and exploitation of this potent compound class. We show here that EasE and EasC are both necessary and sufficient for the production of chanoclavine-I in yeast, and we provide important new information about the involvement of ER and protein folding for proper functional expression of EasE. Moreover, by reconstructing the chanoclavine-I biosynthetic pathway in yeast we demonstrate the advantage and potential of this host, not only as a convenient model system, but also as an alternative cell factory for ergot alkaloid production. PMID- 25112182 TI - Drinking from the Holy Grail: analysis of whole-genome sequencing from the Genetic Analysis Workshop 18. AB - The Genetic Analysis Workshops distribute real and simulated human genetic data to allow the development and comparison of methods to detect genetic variants and genes related to biological traits; the results are then presented and discussed at a biennial meeting. The data made available for Genetic Analysis Workshop 18 (GAW18) included whole-genome sequence data for odd-numbered autosomes from 20 large Mexican American pedigrees selected through probands with type 2 diabetes. Real and simulated blood pressure phenotype data were provided to allow the comparison of methods to detect variants and genes associated with blood pressure. Some of the complexity present in the data includes related individuals, repeated quantitative trait outcomes, covariates, medication effects, pharmacokinetic effects, missing data, admixed population, and imputed genotypes. A wide range of analytic approaches were applied to the data. Contributions that focused only on a subset of up to 155 unrelated subjects from the pedigrees were faced with low power. One recommendation for future analysis is the use of the provided null phenotype to allow comparison of type I error across methods. Collaboration between statistical geneticists and molecular biologists or bioinformaticians would provide helpful input to place variants in genes for gene-based association tests. PMID- 25112183 TI - Methods for collapsing multiple rare variants in whole-genome sequence data. AB - Genetic Analysis Workshop 18 provided whole-genome sequence data in a pedigree based sample and longitudinal phenotype data for hypertension and related traits, presenting an excellent opportunity for evaluating analysis choices. We summarize the nine contributions to the working group on collapsing methods, which evaluated various approaches for the analysis of multiple rare variants. One contributor defined a variant prioritization scheme, whereas the remaining eight contributors evaluated statistical methods for association analysis. Six contributors chose the gene as the genomic region for collapsing variants, whereas three contributors chose nonoverlapping sliding windows across the entire genome. Statistical methods spanned most of the published methods, including well established burden tests, variance-components-type tests, and recently developed hybrid approaches. Lesser known methods, such as functional principal components analysis, higher criticism, and homozygosity association, and some newly introduced methods were also used. We found that performance of these methods depended on the characteristics of the genomic region, such as effect size and direction of variants under consideration. Except for MAP4 and FLT3, the performance of all statistical methods to identify rare casual variants was disappointingly poor, providing overall power almost identical to the type I error. This poor performance may have arisen from a combination of (1) small sample size, (2) small effects of most of the causal variants, explaining a small fraction of variance, (3) use of incomplete annotation information, and (4) linkage disequilibrium between causal variants in a gene and noncausal variants in nearby genes. Our findings demonstrate challenges in analyzing rare variants identified from sequence data. PMID- 25112184 TI - Value of Mendelian laws of segregation in families: data quality control, imputation, and beyond. AB - When analyzing family data, we dream of perfectly informative data, even whole genome sequences (WGSs) for all family members. Reality intervenes, and we find that next-generation sequencing (NGS) data have errors and are often too expensive or impossible to collect on everyone. The Genetic Analysis Workshop 18 working groups on quality control and dropping WGSs through families using a genome-wide association framework focused on finding, correcting, and using errors within the available sequence and family data, developing methods to infer and analyze missing sequence data among relatives, and testing for linkage and association with simulated blood pressure. We found that single-nucleotide polymorphisms, NGS data, and imputed data are generally concordant but that errors are particularly likely at rare variants, for homozygous genotypes, within regions with repeated sequences or structural variants, and within sequence data imputed from unrelated individuals. Admixture complicated identification of cryptic relatedness, but information from Mendelian transmission improved error detection and provided an estimate of the de novo mutation rate. Computationally, fast rule-based imputation was accurate but could not cover as many loci or subjects as more computationally demanding probability-based methods. Incorporating population-level data into pedigree-based imputation methods improved results. Observed data outperformed imputed data in association testing, but imputed data were also useful. We discuss the strengths and weaknesses of existing methods and suggest possible future directions, such as improving communication between data collectors and data analysts, establishing thresholds for and improving imputation quality, and incorporating error into imputation and analytical models. PMID- 25112185 TI - Complex pedigrees in the sequencing era: to track transmissions or decorrelate? AB - Next-generation sequencing (NGS) studies are becoming commonplace, and the NGS field is continuing to develop rapidly. Analytic methods aimed at testing for the various roles that genetic susceptibility plays in disease are also rapidly being developed and optimized. Studies that incorporate large, complex pedigrees are of particular importance because they provide detailed information about inheritance patterns and can be analyzed in a variety of complementary ways. The nine contributions from our Genetic Analysis Workshop 18 working group on family-based tests of association for rare variants using simulated data examined analytic methods for testing genetic association using whole-genome sequencing data from 20 large pedigrees with 200 phenotype simulation replicates. What distinguishes the approaches explored is how the complexities of analyzing familial genetic data were handled. Here, we explore the methods that either harness inheritance patterns and transmission information or attempt to adjust for the correlation between family members in order to utilize computationally and conceptually simpler statistical testing procedures. Although directly comparing these two classes of approaches across contributions is difficult, we note that the two classes balance robustness to population stratification and computational complexity (the transmission-based approaches) with simplicity and increased power, assuming no population stratification or proper adjustment for it (decorrelation approaches). PMID- 25112186 TI - Testing genetic association with rare and common variants in family data. AB - With the advance of next-generation sequencing technologies in recent years, rare genetic variant data have now become available for genetic epidemiology studies. For family samples, however, only a few statistical methods for association analysis of rare genetic variants have been developed. Rare variant approaches are of great interest, particularly for family data, because samples enriched for trait-relevant variants can be ascertained and rare variants are putatively enriched through segregation. To facilitate the evaluation of existing and new rare variant testing approaches for analyzing family data, Genetic Analysis Workshop 18 (GAW18) provided genotype and next-generation sequencing data and longitudinal blood pressure traits from extended pedigrees of Mexican American families from the San Antonio Family Study. Our GAW18 group members analyzed real and simulated phenotype data from GAW18 by using generalized linear mixed-effects models or principal components to adjust for familial correlation or by testing binary traits using a correction factor for familial effects. With one exception, approaches dealt with the extended pedigrees in their original state using information based on the kinship matrix or alternative genetic similarity measures. For simulated data our group demonstrated that the family-based kernel machine score test is superior in power to family-based single-marker or burden tests, except in a few specific scenarios. For real data three contributions identified significant associations. They substantially reduced the number of tests before performing the association analysis. We conclude from our real data analyses that further development of strategies for targeted testing or more focused screening of genetic variants is strongly desirable. PMID- 25112187 TI - Summary of results and discussions from the gene-based tests group at Genetic Analysis Workshop 18. AB - I present a summary of the results and discussions held within the working group on gene-based tests at Genetic Analysis Workshop 18 (GAW18). The main focus of interest in our working group was modeling the action of combinations or "groups" of genetic variants, with a group of variants most often defined as a set of single-nucleotide polymorphisms lying within a known gene. Some contributions investigated the performance of previously proposed methods (particularly rare variant collapsing or burden-type methods) for addressing this question, applied to the GAW18 data, and other contributions developed novel approaches and addressed novel questions. Most approaches were successful in detecting significant effects at MAP4 in the simulated data. No other genetic effects were consistently detected across different analyses. Low power was noted, particularly for those methods that restricted analysis to purely the subset of unrelated individuals. PMID- 25112188 TI - Population-based association and gene by environment interactions in Genetic Analysis Workshop 18. AB - In the past decade, genome-wide association studies have been successful in identifying genetic loci that play a role in many complex diseases. Despite this, it has become clear that for many traits, investigation of single common variants does not give a complete picture of the genetic contribution to the phenotype. Therefore a number of new approaches are currently being investigated to further the search for susceptibility loci or regions. We summarize the contributions to Genetic Analysis Workshop 18 (GAW18) that concern this search using methods for population-based association analysis. Many of the members of our GAW18 working group made use of data types that have only recently become available through the use of next-generation sequencing technologies, with many focusing on the investigation of rare variants instead of or in combination with common variants. Some contributors used a haplotype-based approach, which to date has been used relatively infrequently but may become more important for analyzing rare variant association data. Others analyzed gene-gene or gene-environment interactions, where novel statistical approaches were needed to make the best use of the available information without requiring an excessive computational burden. GAW18 provided participants with the chance to make use of state-of-the-art data, statistical techniques, and technology. We report here some of the experiences and conclusions that were reached by workshop participants who analyzed the GAW18 data as a population-based association study. PMID- 25112189 TI - Local and global ancestry inference and applications to genetic association analysis for admixed populations. AB - Genetic association studies in recently admixed populations offer exciting opportunities to identify novel variants underlying phenotypic diversity. At the same time, genetic heterogeneity resulting from population admixture has to be accounted for to ensure validity of association tests. The whole-genome sequence data and the genome-wide single-nucleotide polymorphism chip data for Mexican American individuals provided by Genetic Analysis Workshop 18 (GAW18) presents a unique opportunity to evaluate and compare methods for the statistical analysis of admixed genetic data. We summarize here the five contributions from the GAW18 working group on admixture mapping and adjusting for admixture. Although group members considered a variety of research topics, the general theme was inference and consideration of ancestry admixture in genetic analyses. The topics considered can be grouped into three categories: (1) global and local ancestry inference and estimation, (2) association and admixture mapping, and (3) genotype imputation in admixed samples. We describe the approaches that were used and the most relevant findings from each contribution. We also provide insight into the strengths and limitations of the state-of-the-art methods considered for genetic analyses in admixed populations. PMID- 25112191 TI - Multivariate analyses of blood pressure related phenotypes in a longitudinal framework: insights from Genetic Analysis Workshop 18. AB - Our working group studied methods for joint analyses of multiple phenotypes using the data provided by Genetic Analysis Workshop 18. Two data sets were available: one containing genotypes obtained from a real human whole-genome sequencing study along with longitudinal measurements on systolic and diastolic blood pressure, age, sex, medication use, and tobacco smoking; and the other a simulated data set using the same set of genotypes and phenotype structure as the real data set. The nine sets of investigators in our working group focused on the statistical challenges posed by association analyses of multivariate phenotypes; they applied a wide spectrum of statistical methods, such as linear mixed models, copula models, and semiparametric regression models for simultaneous analyses of longitudinal data on the two blood pressure phenotypes at the genome-wide level. In this report, we discuss the various strategies explored by the different investigators whose common goal was improving the power to detect association with multivariate phenotypes. PMID- 25112190 TI - Genetic prediction in the Genetic Analysis Workshop 18 sequencing data. AB - High-throughput sequencing data can be used to predict phenotypes from genotypes, and this corresponds to establishing a prognostic model. In extended pedigrees the relatedness of subjects provides additional information so that genetic values, fixed or random genetic components, and heritability can be estimated. At the Genetic Analysis Workshop 18, the working group on genetic prediction dealt with both establishing a prognostic model and, in one contribution, comparing standard logistic regression with robust logistic regression in a sample of unrelated affected or unaffected individuals. Results of both logistic regression approaches were similar. All other contributions to this group used extended family data, in general using the quantitative trait blood pressure. The individual contributions varied in several important aspects, such as the estimation of the kinship matrix and the estimation method. Contributors chose various approaches for model validation, including different versions of cross validation or within-family validation. Within-family validation included model building in the upper generations and validation in later generations. The choice of the statistical model and the computational algorithm had substantial effects on computation time. If decorrelation approaches were applied, the computational burden was substantially reduced. Some software packages estimated negative eigenvalues, although eigenvalues of correlation matrices should be non-negative. Most statistical models and software packages have been developed for experimental crosses and planned breeding programs. With their specialized pedigree structures, they are not sufficiently flexible to accommodate the variability of human pedigrees in general, and improved implementations are required. PMID- 25112192 TI - Longitudinal data analysis in genome-wide association studies. AB - Genome-wide association studies have led to the discovery of thousands of susceptibility genetic variants (typically single-nucleotide polymorphisms [SNPs]) for a wide range of complex diseases and traits commonly measured at a single point in time. Although many novel genotype-phenotype associations have been identified and successfully replicated using cross-sectionally measured phenotypes, there is growing interest in the study of longitudinally measured phenotypes because these allow for the study of the natural trajectory of traits and disease progression. However, there are several challenges with analysis and interpretation of longitudinal data. Here, we summarize the methods and strategies proposed and applied in genome-wide association studies of blood pressure related phenotypes made available through Genetic Analysis Workshop 18 (GAW18). The investigators considered methods that incorporated correlation across time points and familial relatedness among the individuals into their studies and compared their approaches with single-time-point analysis using baseline data. Some of the studies used unrelated individuals; some also used the simulated data provided by the GAW18 organizers to assess type I error and power of their approach in detecting true associations. PMID- 25112193 TI - Longitudinal data analysis for genetic studies in the whole-genome sequencing era. AB - The analysis of whole-genome sequence (WGS) data using longitudinal phenotypes offers a potentially rich resource for the examination of the genetic variants and their covariates that affect complex phenotypes over time. We summarize eight contributions to the Genetic Analysis Workshop 18, which applied a diverse array of statistical genetic methods to analyze WGS data in combination with data from genome-wide association studies (GWAS) from up to four different time points on blood pressure phenotypes. The common goal of these analyses was to develop and apply appropriate methods that utilize longitudinal repeated measures to potentially increase the analytic efficiency of WGS and GWAS data. These diverse methods can be grouped into two categories, based on the way they model dependence structures: (1) linear mixed-effects (LME) models, where the random effect terms in the linear models are used to capture the dependence structures; and (2) variance-components models, where the dependence structures are constructed directly based on multiple components of variance-covariance matrices for the multivariate Gaussian responses. Despite the heterogeneous nature of these analytical methods, the group came to the following conclusions: (1) the use of repeat measurements can gain power to identify variants associated with the phenotype; (2) the inclusion of family data may correct genotyping errors and allow for more accurate detection of rare variants than using unrelated individuals only; and (3) fitting mixed-effects and variance-components models for longitudinal data presents computational challenges. The challenges and computational burden demanded by WGS data were addressed in the eight contributions. PMID- 25112194 TI - Applications of machine learning and data mining methods to detect associations of rare and common variants with complex traits. AB - Machine learning methods (MLMs), designed to develop models using high dimensional predictors, have been used to analyze genome-wide genetic and genomic data to predict risks for complex traits. We summarize the results from six contributions to our Genetic Analysis Workshop 18 working group; these investigators applied MLMs and data mining to analyses of rare and common genetic variants measured in pedigrees. To develop risk profiles, group members analyzed blood pressure traits along with single-nucleotide polymorphisms and rare variant genotypes derived from sequence and imputation analyses in large Mexican American pedigrees. Supervised MLMs included penalized regression with varying penalties, support vector machines, and permanental classification. Unsupervised MLMs included sparse principal components analysis and sparse graphical models. Entropy-based components analyses were also used to mine these data. None of the investigators fully capitalized on the genetic information provided by the complete pedigrees. Their approaches either corrected for the nonindependence of the individuals within the pedigrees or analyzed only those who were independent. Some methods allowed for covariate adjustment, whereas others did not. We evaluated these methods using a variety of metrics. Four contributors conducted primary analyses on the real data, and the other two research groups used the simulated data with and without knowledge of the underlying simulation model. One group used the answers to the simulated data to assess power and type I errors. Although the MLMs applied were substantially different, each research group concluded that MLMs have advantages over standard statistical approaches with these high-dimensional data. PMID- 25112196 TI - Challenges of linkage analysis in the era of whole-genome sequencing. AB - Whole-genome sequencing (WGS) is becoming an affordable technology for the study of the genetics of complex traits. With any new technology, experimental designs and statistical methods, both old and new, must be evaluated. One design seeing a resurgence of interest is the use of families. Genetic Analysis Workshop 18 provided the opportunity to evaluate statistical methods applied to WGS data for family-based studies. We summarize the results of five contributions that used linkage in the context of WGS. The investigators took differing approaches, including assessment of false-positive rates in classic two-point linkage, the effects of heterogeneity on linkage and association tests, and the use of linkage to focus association tests. We describe the primary findings of each contribution and note challenges that are not new to those working in family designs or specific to WGS data; for example, choice of phenotype definition, covariate adjustment, and use of longitudinal data may produce different results, making comparisons challenging. We detail new issues brought about by WGS, such as the elevated genome-wide false-positive rate for classic two-point parametric linkage analysis, computational demands in multipoint calculations, and lack of clarity in how to best use linkage to focus association testing. Finally, we comment on when linkage may be helpful for WGS, highlighting where additional research is needed; for example, although linkage analysis has been successful in the study of rare variants of large effect, how to best use family information in the context of rare variants of moderate effect remains an open research question. PMID- 25112195 TI - Pathway analysis approaches for rare and common variants: insights from Genetic Analysis Workshop 18. AB - Pathway analysis, broadly defined as a group of methods incorporating a priori biological information from public databases, has emerged as a promising approach for analyzing high-dimensional genomic data. As part of Genetic Analysis Workshop 18, seven research groups applied pathway analysis techniques to whole-genome sequence data from the San Antonio Family Study. Overall, the groups found that the potential of pathway analysis to improve detection of causal variants by lowering the multiple-testing burden and incorporating biologic insight remains largely unrealized. Specifically, there is a lack of best practices at each stage of the pathway approach: annotation, analysis, interpretation, and follow-up. Annotation of genetic variants is inconsistent across databases, incomplete, and biased toward known genes. At the analysis stage insufficient statistical power remains a major challenge. Analyses combining rare and common variants may have an inflated type I error rate and may not improve detection of causal genes. Inclusion of known causal genes may not improve statistical power, although the fraction of explained phenotypic variance may be a more appropriate metric. Interpretation of findings is further complicated by evidence in support of interactions between pathways and by the lack of consensus on how to best incorporate functional information. Finally, all presented approaches warranted follow-up studies, both to reduce the likelihood of false-positive findings and to identify specific causal variants within a given pathway. Despite the initial promise of pathway analysis for modeling biological complexity of disease phenotypes, many methodological challenges currently remain to be addressed. PMID- 25112197 TI - Clinical behavior of Japanese community pharmacists for preventing prescription drug overdose. AB - AIM: Prescription drug abuse, including benzodiazepines, is a growing health problem in Japan. This study examined the community pharmacist's clinical behavior regarding patients who overdose on prescribed drugs, and explored the possibility of overdose prevention by community pharmacists. METHODS: We surveyed all registered community pharmacies with dispensing functions (n = 1867) in the Saitama Pharmaceutical Association. An anonymous self-administered questionnaire was mailed to each pharmacy. Respondents were asked about clinical behavior such as medication counseling and referral to the prescriber if prescription drug overdose was identified. RESULTS: Among respondents, 26% of community pharmacists reported clinical experience of working with patients who overdosed on prescribed drugs in the previous year. Half of respondents evaluated their practice such as medication counseling and referral to the prescriber as 'good'. On multivariate analysis, a 'poor' self-evaluation of referral to the prescriber was significantly associated with the following perceptions: 'insufficient confidence in communication with prescribers' (odds ratio [OR], 2.7; 95% confidence interval [95%CI]: 1.4-5.3), and 'to avoid trouble with prescribers' (OR, 1.7; 95%CI: 1.0 2.7). CONCLUSION: Japanese community pharmacists could prevent prescription drug abuse in their practice, but the pharmacists who have insufficient confidence in communication with prescribers and who are afraid of trouble with a prescriber, reported poor self-evaluation for referral to the prescribers. All prescribers should understand the importance of referral by community pharmacists, to assist community pharmacists in playing a critical role in prevention of prescription drug abuse. PMID- 25112198 TI - Analysis of tramadol and O-desmethyltramadol in decomposed skeletal tissues following acute and repeated tramadol exposure by gas chromatography mass spectrometry. AB - Decomposed bone and plasma samples of rats exposed to tramadol (TRAM) under different dosing patterns were analyzed. Wistar rats received TRAM as one acute dose (n=4, 45 mg/kg, i.p.) or three doses (n=4, 15 mg/kg, i.p.), 40 min apart. Perimortem heart blood was collected, rats were euthanized and placed outdoors to decompose to skeleton. Recovered bone was ground and subjected to methanolic extraction. Bone extracts and plasma samples underwent solid phase extraction and were analyzed using gas chromatography-mass spectrometry. Levels of TRAM and the primary metabolite O-desmethyltramadol (ODMT) were expressed as mass normalized response ratios (RR/m). Levels (RR/m) for TRAM and ODMT did not differ significantly between exposure types in any of the bone types examined or for the pooled bone comparisons (Mann-Whitney, p>0.05). However, ratios of analyte levels (RRTRAM/RRODMT) differed significantly between exposure patterns for tibial and skull bone as well as for pooled bone comparisons (Mann-Whitney, p<0.05). Levels of TRAM and ODMT, as well as ratios of analyte levels (RRTRAM/RRODMT), differed significantly in plasma between exposure patterns. Bone TRAM and ODMT levels were poorly correlated to corresponding plasma levels (TRAM: r=0.33-0.57; ODMT: r= 0.35-0.23). PMID- 25112199 TI - Fluorescent dye ProteoStat to detect and discriminate intracellular amyloid-like aggregates in Escherichia coli. AB - The formation of amyloid aggregates is linked to the onset of an increasing number of human disorders. Thus, there is an increasing need for methodologies able to provide insights into protein deposition and its modulation. Many approaches exist to study amyloids in vitro, but the techniques available for the study of amyloid aggregation in cells are still limited and non-specific. In this study we developed a methodology for the detection of amyloid-like aggregates inside cells that discriminates these ordered assemblies from other intracellular aggregates. We chose bacteria as model system, since the inclusion bodies formed by amyloid proteins in the cytosol of bacteria resemble toxic amyloids both structurally and functionally. Using confocal microscopy, fluorescence spectroscopy, and flow cytometry, we show that the recently developed red fluorescent dye ProteoStat can detect the presence of intracellular amyloid-like deposits in living bacterial cells with high specificity, even when the target proteins are expressed at low levels. This methodology allows quantitation of the intracellular amyloid content, shows the potential to replace in vitro screenings in the search for therapeutic anti-amyloidogenic compounds, and might be useful for identifying conditions that prevent the aggregation of therapeutic recombinant proteins. PMID- 25112201 TI - QTL analysis of flowering time and ripening traits suggests an impact of a genomic region on linkage group 1 in Vitis. AB - In the recent past, genetic analyses of grapevine focused mainly on the identification of resistance loci for major diseases such as powdery and downy mildew. Currently, breeding programs make intensive use of these results by applying molecular markers linked to the resistance traits. However, modern genetics also allows to address additional agronomic traits that have considerable impact on the selection of grapevine cultivars. In this study, we have used linkage mapping for the identification and characterization of flowering time and ripening traits in a mapping population from a cross of V3125 ('Schiava Grossa' * 'Riesling') and the interspecific rootstock cultivar 'Borner' (Vitis riparia * Vitis cinerea). Comparison of the flowering time QTL mapping with data derived from a second independent segregating population identified several common QTLs. Especially a large region on linkage group 1 proved to be of special interest given the genetic divergence of the parents of the two populations. The proximity of the QTL region contains two CONSTANS-like genes. In accordance with data from other plants such as Arabidopsis thaliana and Oryza sativa, we hypothesize that these genes are major contributors to control the time of flowering in Vitis. PMID- 25112200 TI - Identification and characterization of unrecognized viruses in stool samples of non-polio acute flaccid paralysis children by simplified VIDISCA. AB - BACKGROUND: The use of sequence independent methods combined with next generation sequencing for identification purposes in clinical samples appears promising and exciting results have been achieved to understand unexplained infections. One sequence independent method, Virus Discovery based on cDNA Amplified Fragment Length Polymorphism (VIDISCA) is capable of identifying viruses that would have remained unidentified in standard diagnostics or cell cultures. METHODS: VIDISCA is normally combined with next generation sequencing, however, we set up a simplified VIDISCA which can be used in case next generation sequencing is not possible. Stool samples of 10 patients with unexplained acute flaccid paralysis showing cytopathic effect in rhabdomyosarcoma cells and/or mouse cells were used to test the efficiency of this method. To further characterize the viruses, VIDISCA-positive samples were amplified and sequenced with gene specific primers. RESULTS: Simplified VIDISCA detected seven viruses (70%) and the proportion of eukaryotic viral sequences from each sample ranged from 8.3 to 45.8%. Human enterovirus EV-B97, EV-B100, echovirus-9 and echovirus-21, human parechovirus type-3, human astrovirus probably a type-3/5 recombinant, and tetnovirus-1 were identified. Phylogenetic analysis based on the VP1 region demonstrated that the human enteroviruses are more divergent isolates circulating in the community. CONCLUSION: Our data support that a simplified VIDISCA protocol can efficiently identify unrecognized viruses grown in cell culture with low cost, limited time without need of advanced technical expertise. Also complex data interpretation is avoided thus the method can be used as a powerful diagnostic tool in limited resources. Redesigning the routine diagnostics might lead to additional detection of previously undiagnosed viruses in clinical samples of patients. PMID- 25112202 TI - Mapping resistance to the bird cherry-oat aphid and the greenbug in wheat using sequence-based genotyping. AB - KEY MESSAGE: Identification of novel resistance QTL against wheat aphids. First QTL-resistance report for R. padi in wheat and chromosome 2DL for S. graminum . These sources have potential use in wheat breeding. The aphids Rhopalosiphum padi and Schizaphis graminum are important pests of common wheat (Triticum aestivum L.). Characterization of the genetic bases of resistance sources is crucial to facilitate the development of resistant wheat cultivars to these insects. We examined 140 recombinant inbred lines (RILs) from the cross of Seri M82 wheat (susceptible) with the synthetic hexaploid wheat CWI76364 (resistant). RILs were phenotyped for R. padi antibiosis and tolerance traits. Phenotyping of S. graminum resistance was based on leaf chlorosis in a greenhouse screening and the number of S. graminum/tiller in the field. RILs were also scored for pubescence. Using a sequence-based genotyping method, we located genomic regions associated with these resistance traits. A quantitative trait locus (QTL) for R. padi antibiosis (QRp.slu.4BL) that explained 10.2 % of phenotypic variation was found in chromosome 4BL and located 14.6 cM apart from the pubescence locus. We found no association between plant pubescence and the resistance traits. We found two QTLs for R. padi tolerance (QRp.slu.5AL and QRp.slu.5BL) in chromosomes 5AL and 5BL, with an epistatic interaction between a locus in chromosome 3AL (EnQRp.slu.5AL) and QRp.slu.5AL. These genomic regions explained about 35 % of the phenotypic variation. We re-mapped a previously reported gene for S. graminum resistance (putatively Gba) in 7DL and found a novel QTL associated with the number of aphids/tiller (QGb.slu-2DL) in chromosome 2DL. This is the first report on the genetic mapping of R. padi resistance in wheat and the first report where chromosome 2DL is shown to be associated with S. graminum resistance. PMID- 25112203 TI - Lr70, a new gene for leaf rust resistance mapped in common wheat accession KU3198. AB - KEY MESSAGE: KU3198 is a common wheat accession that carries one novel leaf rust resistance (Lr) gene, Lr70 , and another Lr gene which is either novel, Lr52 or an allele of Lr52. Leaf rust, caused by Puccinia triticina Eriks. (Pt), is a broadly distributed and economically important disease of wheat. Deploying cultivars carrying effective leaf rust resistance (Lr) genes is a desirable method of disease control. KU3198 is a common wheat (Triticum aestivum L.) accession from the Kyoto collection that was highly resistant to Pt in Canada. An F2 population from the cross HY644/KU3198 showed segregation for two dominant Lr genes when tested with Pt race MBDS which was virulent on HY644. Multiple bulk segregant analysis (MBSA) was employed to find putative chromosome locations of these Lr genes using SSR markers that provided coverage of the genome. MBSA predicted that the Lr genes were located on chromosomes 5B and 5D. A doubled haploid population was generated from the cross of JBT05-714 (HY644*3/KU3198), a line carrying one of the Lr genes from KU3198, to Thatcher. This population segregated for a single Lr gene conferring resistance to Pt race MBDS, which was mapped to the terminal region of the short arm of chromosome 5B with SSR markers and given the temporary designation LrK1. One F3 family derived from the HY644/KU3198 F2 population that segregated only for the second Lr gene from KU3198 was identified. This family was treated as an F2-equivalent population and used for mapping the Lr gene, which was located to the terminal region of chromosome 5DS. As no other Lr gene has been mapped to 5DS, this gene is novel and has been designated as Lr70. PMID- 25112204 TI - Mapping of quantitative adult plant field resistance to leaf rust and stripe rust in two European winter wheat populations reveals co-location of three QTL conferring resistance to both rust pathogens. AB - KEY MESSAGE: We detected several, most likely novel QTL for adult plant resistance to rusts. Notably three QTL improved resistance to leaf rust and stripe rust simultaneously indicating broad spectrum resistance QTL. The rusts of wheat (Puccinia spp.) are destructive fungal wheat diseases. The deployment of resistant cultivars plays a central role in integrated rust disease management. Durability of resistance would be preferred, but is difficult to analyse. The Austrian winter wheat cultivar Capo was released in the 1989 and grown on a large acreage during more than two decades and maintained a good level of quantitative leaf rust and stripe rust resistance. Two bi-parental mapping populations: Capo * Arina and Capo * Furore were tested in multiple environments for severity of leaf rust and stripe rust at the adult plant stage in replicated field experiments. Quantitative trait loci associated with leaf rust and stripe rust severity were mapped using DArT and SSR markers. Five QTL were detected in multiple environments associated with resistance to leaf rust designated as QLr.ifa-2AL, QLr.ifa-2BL, QLr.ifa-2BS, QLr.ifa-3BS, and QLr.ifa-5BL, and five for resistance to stripe rust QYr.ifa-2AL, QYr.ifa-2BL, QYr.ifa-3AS, QYr.ifa-3BS, and QYr.ifa 5A. For all QTL apart from two (QYr.ifa-3AS, QLr.ifa-5BL) Capo contributed the resistance improving allele. The leaf rust and stripe rust resistance QTL on 2AL, 2BL and 3BS mapped to the same chromosome positions, indicating either closely linked genes or pleiotropic gene action. These three multiple disease resistance QTL (QLr.ifa-2AL/QYr.ifa-2AL, QLr.ifa.2BL/QYr.ifa-2BL, QLr.ifa-3BS/QYr.ifa.3BS) potentially contribute novel resistance sources for stripe rust and leaf rust. The long-lasting resistance of Capo apparently rests upon a combination of several genes. The described germplasm, QTL and markers are applicable for simultaneous resistance improvement against leaf rust and stripe rust. PMID- 25112205 TI - Mapping resistance genes for Oculimacula acuformis in Aegilops longissima. AB - KEY MESSAGE: This study identified three QTL conferring resistance to Oculimacula acuformis in Aegilops longissima and their associated markers, which can be useful in marker-assisted selection breeding for eyespot resistance. Oculimacula acuformis is one of two species of soilborne fungi that cause eyespot of wheat, the other being Oculimacula yallundae. Both pathogens can coexist in the same field and produce elliptical lesions on stem bases of wheat that are indistinguishable. Pch1 and Pch2 are the only two eyespot resistance genes readily available to wheat breeders, but neither provides complete control. A new source of eyespot resistance was identified from Aegilops longissima (2n = 14, S(l)S(l)), a wild relative of wheat. Three QTL for resistance to O. acuformis were mapped in chromosomes 1S(l), 3S(l), and 5S(l) using a recombinant inbred line population developed from the cross Ae. longissima accessions PI 542196 (R) * PI 330486 (S). The three QTL explained 66 % of phenotypic variation by beta glucuronidase score (GUS) and 84 % by visual rating. These QTL had LOD values of 10.6, 8.8, and 6.0 for GUS score, and 16.0, 10.0, and 13.0 for visual rating. QTL associated with resistance to O. acuformis have similar chromosomal locations as some for resistance to O. yallundae, except that a QTL for resistance to O. yallundae was found in chromosome 7S(l) but not for O. acuformis. Thus, it appears that some genes at the same locus in Ae. longissima may control resistance to both eyespot pathogens. QTL effective against both pathogens will be most useful for breeding programs and have potential to improve the effectiveness and genetic diversity of eyespot resistance. PMID- 25112207 TI - A fast way to fluorescence: a fourfold domino reaction to condensed polycyclic compounds. AB - A fast and efficient palladium-catalyzed fourfold domino Sonogashira/double carbopalladation/C?H-activation reaction that converts simple aromatic systems into complex polycyclic hydrocarbons has been developed. A number of substituted products has thus been prepared in yields up to 89 %. The structural assignment has been confirmed by using single-crystal X-ray crystallography. The products show intriguing fluorescence activity and thus might serve as chemical sensors or fluorescent imaging dyes. PMID- 25112206 TI - The dynamic influence of emotional words on sentence processing. AB - In the present study, we aimed to examine how the emotionality of words influences online sentence processing-specifically, the influence of emotional words on the processing of following words in sentences. We manipulated the emotionality of verbs as well as the orthographic correctness of their following (neutral) object nouns, so that the orthographic violation of the (neutral) nouns occurred in either emotional or neutral sentences. Event-related potentials (ERPs) were recorded to both the nouns and the verbs. We found that the orthographic violation of the nouns elicited a P2 and an N400 effect in the emotionally neutral sentences, but an LPC effect in the emotionally charged sentences. We also found that the emotional verbs elicited a larger N1, a larger P2, and a larger N400 than did the neutral verbs. The ERP results suggest that emotional words capture more attention than neutral words, which further affects early orthographic analysis of the following words. Our findings demonstrate a dynamic influence of emotional words on sentence processing. PMID- 25112208 TI - High-throughput method of dioxin analysis in aqueous samples using consecutive solid phase extraction steps with the new C18 UltraflowTM pressurized liquid extraction and automated clean-up. AB - A high-throughput analytical method has been developed for the determination of seventeen 2,3,7,8-substituted congeners of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in aqueous samples. A recently introduced octadecyl (C18) disk for semi-automated solid-phase extraction of PCDD/Fs in water samples with a high level of particulate material has been tested for the analysis of dioxins. A new type of C18 disk specially designed for the analysis of hexane extractable material (HEM), but never previously reported for use in PCDD/Fs analysis. This kind of disk allows a higher filtration flow, and therefore the time of analysis is reduced. The solid-phase extraction technique is used to change samples from liquid to solid, and therefore pressurized liquid extraction (PLE) can be used in the pre-treatment. In order to achieve efficient purification, extracts from the PLE are purified using an automated Power-prep system with disposable silica, alumina, and carbon columns. Quantitative analyses of PCDD/Fs were performed by GC-HRMS using multi-ion detection (MID) mode. The method was successfully applied to the analysis of water samples from the wastewater treatment system of a vinyl chloride monomer plant. The entire procedure is in agreement with EPA1613 recommendations regarding the blank control, MDLs (method detection limits), accuracy, and precision. The high-throughput method not only meets the requirements of international standards, but also shortens the required analysis time from 2 weeks to 3d. PMID- 25112209 TI - Asymmetries in explosive strength following anterior cruciate ligament reconstruction. AB - BACKGROUND: Despite its apparent functional importance, there is a general lack of data regarding the time-related changes in explosive strength and the corresponding side-to-side asymmetries in individuals recovering from an ACL reconstruction (ACLR). The present study was designed to assess changes in the maximum and explosive strength of the quadriceps and hamstring muscles in athletes recovering from an ACLR. METHODS: Twenty male athletes with an ACL injury completed a standard isometric testing protocol pre-ACLR, four and sixmonths post-ACLR. In addition to the maximum strength (Fmax), the explosive strength of quadriceps and hamstrings was assessed through four variables derived from the slope of the force-time curves over various time intervals (RFDmax, RFD50, RFD150 and RFD250). Side-to-side asymmetries were calculated relative to post-ACLR measures of the uninvolved leg ("standard" asymmetries), and relative to pre-ACLR value of the uninvolved leg ("real" asymmetries). RESULTS: Pre-ACLR asymmetries in quadriceps RFD (average 26%) were already larger than in Fmax (14%) (p<0.05). Six months post-ACLR real asymmetries in RFD variables (33-39%) were larger than the corresponding standard asymmetries (26-28%; p<0.01). Average asymmetries in hamstrings' RFD and Fmax were 10%, 25% and 15% for pre-ACLR and two post-ACLR sessions, respectively (all p>0.05). CONCLUSIONS: In addition to the maximum strength, the indices of explosive strength should also be included in monitoring recovery of muscle function following an ACLR. Furthermore, pre injury/reconstruction values should be used for the post-ACLR side-to-side comparisons, providing a more valid criterion regarding the muscle recovery and readiness for a return to sports. PMID- 25112210 TI - Synovial fluid differential cell count in wear debris synovitis after total knee replacement. AB - BACKGROUND: Determining the cause of synovitis following total knee arthroplasty (TKA) can be challenging. The differential diagnoses include infection, hemarthrosis, instability, crystalline disease, wear debris or idiopathic causes. Wear particle synovitis can mimic periprosthetic infection with symptoms of pain and effusion. Radiographs and physical exam are often inconclusive in differentiating the two. Synovial fluid analysis is routinely used in evaluating periprosthetic infections. We examined the association between synovial white blood cell count and differentials, and polyethylene wear and osteolysis, to see if fluid analysis can aid in establishing the diagnosis of wear particle synovitis. METHODS: A cell count and differential was obtained from synovial fluid samples from 54 TKAs undergoing revision for aseptic failure. Explanted polyethylene inserts were analyzed for linear and volumetric wear, oxidation (ketone peak height), and damage features. Analysis was performed to assess the relationship between cell counts and polyethylene wear indicators as well as severity of intra-operative and radiographic osteolysis. RESULTS: Total and percent mononuclear (monocyte and lymphocyte) cell counts were found to be elevated in the presence of documented wear debris synovitis and an association was suggested between their levels and maximum ketone levels. CONCLUSION: The present study implies that the differential cell count of knee fluid can help distinguish wear debris from infection as a source of synovitis following TKA and identifies the value of the mononuclear cell count as a possible tool to assess abnormal wear rates of the polyethylene insert. Further research into identifying the exact role of monocytes in the wear debris synovitis and osteolytic pathways is warranted. LEVEL OF EVIDENCE: Level II, diagnostic study. PMID- 25112212 TI - Histological features of the ACL remnant in partial tears. AB - BACKGROUND: The aim of this study was to investigate the histological features of the remaining fibers bridging the femur and tibia in partial ACL tears. METHODS: Twenty-six ACL remnants were harvested from patients who had arthroscopic criteria concordant with a partial tear. Histological analysis includes cellularity, blood vessel density evaluation and characterization of the femoral bony insertion morphology. Immunohistochemical studies were carried out to determine cells positive for alpha-smooth actin and for mechanoreceptor detection. RESULTS: In these samples, a normal femoral insertion of the remnant was present in 22.7% of the cases. In 54% of the samples, substantial areas of hypercellularity were observed. Myofibroblasts were the predominant cell type and numerous cells positive for alpha-smooth actin were detected at immunostaining. Blood vessel density was increased in hypercellularity areas and in the synovial sheet. Free nerve endings and few Golgi or Ruffini corpuscles were detected in 41% of the specimens. The cellularity was correlated to the time between injury to surgery (p=0.001). CONCLUSION: Competent histological structures including a well-vascularized synovial sheet, numerous fibroblasts and myofibroblasts and mechanoreceptors were found in ACL remnants. These histological findings bring additional knowledge towards the preservation of the ACL remnant in partial tears when ACL reconstruction or augmentation is considered. CLINICAL RELEVANCE: Descriptive laboratory study. PMID- 25112211 TI - Relationship of the posterior femoral axis of the "kinematically aligned" total knee arthroplasty to the posterior condylar, transepicondylar, and anteroposterior femoral axes. AB - BACKGROUND: A recent proposed modification in surgical technique in total knee arthroplasty (TKA) has been the introduction of the "kinematically aligned" TKA, in which the angle and level of the posterior joint line of the femoral component and joint line of the tibial component are aligned to those of the "normal," pre arthritic knee. The purpose of this study was to establish the relationship of the posterior femoral axis of the "kinematically aligned" total knee arthroplasty (TKA) to the traditional axes used to set femoral component rotation. METHODS: One hundred and fourteen consecutive, unselected patients with preoperative MRI images undergoing TKA were retrospectively reviewed. The transepicondylar axis (TEA), posterior condylar axis (PCA), antero-posterior axis (APA) of the trochlear groove, and posterior femoral axis of the kinematically aligned TKA (KAA) were templated on axial MRI images by two independent observers. The relationships between the KAA, TEA, APA, and PCA were determined, with a negative value indicating relative internal rotation of the axis. RESULTS: On average, the KAA was 0.5 degrees externally rotated relative to the PCA (minimum of -3.6 degrees , maximum of 5.8 degrees ), -4.0 degrees internally rotated relative to the TEA (minimum of -10.5 degrees , maximum of 2.3 degrees ), and -96.4 degrees internally rotated relative to the APA (minimum of -104.5 degrees , maximum of 88.5 degrees ). Each of these relationships exhibited a wide range of potential values. CONCLUSIONS: Using a kinematically aligned surgical technique internally rotates the posterior femoral axis relative to the transepicondylar axis, which significantly differs from current alignment instrument targets. PMID- 25112213 TI - Sarcocystis arieticanis (Apicomplexa: Sarcocystidae) infecting the heart muscles of the domestic sheep, Ovis aries (Artiodactyla: Bovidae), from K. S. A. on the basis of light and electron microscopic data. AB - In the present study, the heteroxenous life cycle of Sarcocystis species from three strains of the slaughtered sheep at Al-Azizia and Al-Saada abattoirs in Riyadh city, K.S.A., was studied. Muscle samples of the oesophagus, diaphragm, tongue, skeletal and heart muscles were examined. Varied natural infection rates in the muscles of the examined sheep strains were recorded as 83% in Niemy, 81.5% in Najdy and 90% in Sawakny sheep. Muscles of the diaphragm showed the highest infection level above all organs except Najdy sheep in which oesophagus has the highest rate. Also, the heart was the lowest infected organ (40% Niemy, 44% Najdy and 53% Sawakny). Microscopic sarcocysts of Sarcocystis arieticanis are easily identified in sections through the heart muscles of the domestic sheep Ovis aries (Artiodactyla: Bovidae). Cysts measured 38.5-64.4 MUm (averaged 42.66 MUm) in width and 62.4-173.6 MUm (averaged 82.14 MUm) in length. The validity of this species was confirmed by means of ultrastructural characteristics of the primary cyst wall (0.1-0.27 MUm thick) which revealed the presence of irregularly shaped crowded and hairy-like projections underlined by a thin layer of ground substance. This layer consisted mainly of fine, dense homogenous granules enclosing the developing metrocytes and merozoites that usually contain nearly all the structures of the apical complex and fill the interior cavity of the cyst. Several septa derived from the ground substance divided the cyst into compartments. The merozoites were banana-shaped and measured 12-16 MUm in length with centrally or posteriorly located nuclei. Experimental infection of carnivores by feeding heavily infected sheep muscles revealed that the dog, Canis familiaris, is the only final host of the present Sarcocystis species. Gamogony, sporogonic stages and characteristics of sporulated oocysts were also investigated. PMID- 25112214 TI - Clamp ultrastructure of the basal monogenean Chimaericola leptogaster (Leuckart, 1830) (Polyopisthocotylea: Chimaericolidae). AB - The ultrastructure of the haptoral clamps of the chimaericolid monogenean Chimaericola leptogaster, a basal polyopisthocotylean from the gills of a holocephalan fish, is described. These clamps are characterized by the presence of two muscle blocks interrupted mid-anteriorly and mid-posteriorly and different kinds of hard structures: a single median and paired lateral sclerites embedded in the clamp wall; six spine-like structures directed towards the clamp lumen; and electron dense surface structures along the internal surface of the anterior clamp lips and along the luminal surface of the tegument of the clamp lumen. The lateral sclerites are situated deep within muscular tissue and are closely bounded by radial myofibrils, possessing a uniform electron dense matrix within which are hollow areas of different sizes. The median sclerite occupies an area between the clamp wall myofibrils and the luminal epithelium, is surrounded by a basement lamina and is composed of a heterogeneous matrix comprising two different morphological layers related to variations in the type and concentration of fibrils. Four of the spine-like structures are extensions of the margins of the two spindle-like muscle blocks in the clamps, i.e. the two anterior and two posterior structures, and the two others are situated at the lateral constrictions of the left and right muscle blocks. The electron dense surface structures are derivations of the clamp tegument or, to be more precise, its outer, densely fibrous region. These results are discussed in relation to the evidence that the haptoral clamps of C. leptogaster are apparently ancient origin. PMID- 25112215 TI - The role of quorum sensing system in antimicrobial induced ampC expression in Pseudomonas aeruginosa biofilm. AB - The aim of this study was to evaluate the effects of quorum sensing (QS) systems in Pseudomonas aeruginosa (P. aeruginosa) on the expression of ampC gene induced by antibiotics. An in vitro dynamic model of P. aeruginosa biofilms was established in a silicon tube in once-flowthrough system at 37 degrees C. Biofilm generation was identified by argentation. Biofilm morphology of standard P. aeruginosa strain (PAO-1) and QS systems deficient strains (PDO100, rhlI deficient strain; PAO-JP1, lasI deficient strain; and PAO-MW1, rhlI and lasI deficient strain) were observed by optical microscope. The expression of ampC in PAO1, PAO1 with QS inhibitor (furanone C-30) and the QS deficient strains before and after induced by antibiotics were quantified by real-time quantitative PCR. The biofilms of PAO-1 and PDO100 were much thicker and denser than that of PAO JP1 and PAO-MW1. Being induced by antibiotics, the expression of ampC in PAO1 and PDO100 was significantly higher than that in PAO-MW1 and PAO-JP1. With the effect of furanone C-30, the expression of ampC in PAO1 induced by antibiotics was reduced in a dose-dependent manner. QS system, especially the las system, plays an important role in both biofilm formation and antimicrobials induced ampC expression and furanone C-30 is a potent inhibitor for P. aeruginosa QS system. PMID- 25112216 TI - Cell penetration: scope and limitations by the application of cell-penetrating peptides. AB - The penetration of polar or badly soluble compounds through a cell membrane into live cells requires mechanical support or chemical helpers. Cell-penetrating peptides (CPPs) are very promising chemical helpers. Because of their low cytotoxicity and final degradation to amino acids, they are particularly favored in in vivo studies and for clinical applications. Clearly, the future of CPP research is bright; however, the required optimization studies for each drug require considerable individualized attention. Thus, CPPs are not the philosopher's stone. As of today, a large number of such transporter peptides with very different sequences have been identified. These have different uptake mechanisms and can transport different cargos. Intracellular concentrations of cargos can reach a low micromole range and are able to influence intracellular reactions. Internalized ribonucleic acids such as small interfering RNA (siRNA) and mimics of RNA such as peptide nucleic acids, morpholino nucleic acids, and triesters of oligonucleotides can influence transcription and translation. Despite the highly efficient internalization of antibodies, enzymes, and other protein factors, as well as siRNA and RNA mimics, the uptake and stabile insertion of DNA into the genome of the host cells remain substantially challenging. This review describes a wide array of differing CPPs, cargos, cell lines, and tissues. The application of CPPs is compared with electroporation, magnetofection, lipofection, viral vectors, dendrimers, and nanoparticles, including commercially available products. The limitations of CPPs include low cell and tissue selectivity of the first generation and the necessity for formation of fusion proteins, conjugates, or noncovalent complexes to different cargos and of cargo release from intracellular vesicles. Furthermore, the noncovalent complexes require a strong molar excess of CPPs, and extensive experimentation is required to determine the most optimal CPP for any given cargo and cell type. Yet to predict which CPP is optimal for any given target remains a complex question. More recently, there have been promising developments: the enhancement of cell specificity using activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, and the transport of drugs through blood-brain barriers, through the conjunctiva of eyes, skin, and into nerve cells. Proteins, siRNA, and mimics of oligonucleotides can be efficiently transported into cells and have been tested for treatment of certain diseases. The recent state of the art in CPP research is discussed together with the overall scope, limitations, and some recommendations for future research directions. PMID- 25112217 TI - Comorbid Problem Gambling and Major Depression in a Community Sample. AB - Major depression is among the most common comorbid conditions in problem gambling. However, little is known about the effects of comorbid depression on problem gambling. The present study examined the prevalence of current major depression among problem gamblers (N = 105) identified from a community sample of men and women in Alberta, and examined group differences in gambling severity, escape motivation for gambling, family functioning, childhood trauma, and personality traits across problem gamblers with and without comorbid depression. The prevalence of major depression among the sample of problem gamblers was 32.4%. Compared to problem gamblers without depression (n = 71), problem gamblers with comorbid depression (n = 34) reported more severe gambling problems, greater history of childhood abuse and neglect, poorer family functioning, higher levels of neuroticism, and lower levels of extraversion, agreeableness, and conscientiousness. Furthermore, the problem gamblers with comorbid depression had greater levels of childhood abuse and neglect, worse family functioning, higher neuroticism, and lower agreeableness and conscientiousness than a comparison sample of recreational gamblers with depression (n = 160). These findings underscore the need to address comorbid depression in assessment and treatment of problem gambling and for continued research on how problem gambling is related to frequently co-occurring disorders such as depression. PMID- 25112219 TI - Gender Differences in Risk Aversion Among Chinese University Students. AB - This paper examines gender differences in risk aversion among Chinese university students. Chinese females are proposed to be more risk averse and require a higher risk premium when faced with a gamble option in the gain-domain frame as compared to Chinese males. Two groups of 100 participants each (male = 100 and female = 100 in total) were recruited to fill up questionnaires that included items relating to objective probability lotteries. Within each group, it was found that Chinese males and females did not differ in their risk aversion. However, results show that Chinese males tend to react more readily to rising risk premium by taking up options with higher expected values when compared to Chinese females. Current findings will have useful implications to marketers (particularly, promoters of gambling products) and problem gambling counselors. PMID- 25112218 TI - The Relationship Between Gambling and Homelessness: A Commentary on Sharman et al. (2014). AB - The relationship between problem gambling and homelessness is a little studied area in the gambling studies field. A recent study by Sharman et al. (J Gambl Stud, doi: 10.1007/s10899-014-9444-7, 2014) is the first quantitative study in Great Britain on this interesting and important topic. In this context, the study is to be commended and provides an empirical benchmark on which other studies can build. The study reported a problem gambling prevalence rate of 11.6% and is significantly higher than the problem gambling rate of the general population in Great Britain (which is <1%). However, given the political sensitivity surrounding the expansion of bookmakers in the UK, the study needs further contextualization otherwise the findings of such studies may be used by anti gambling lobby groups to serve their own political agendas. While it is good that such an area has been empirically investigated in Great Britain, this paper briefly (1) places the issue of problem gambling among the homeless into the wider context of problems among the homeless more generally (particularly in relation to mental health problems and other addictive behaviors), (2) highlights some of the methodological problems and weaknesses of the study, and (3) notes a number of factual errors made in the paper. PMID- 25112220 TI - A Resource Model of Change: Client Factors that Influence Problem Gambling Treatment Outcomes. AB - This study examined a resource-based model of change whereby poor problem gambling (PG) treatment outcomes and relapse are viewed as resulting from client coping resources being diminished or overwhelmed. Specifically, client factors that work like resources to facilitate treatment (i.e., social support, self efficacy, motivation, readiness for change, and emotion-focused coping) or use up resources and hinder treatment (i.e., co-morbid depression and life stress) were examined. The 50 participants were followed for 4 months after entering treatment for PG and were assessed at baseline, 1 month into treatment, 2 months into treatment, and during a follow-up 4 months after treatment began. Of the 50 participants, 20 dropped-out of treatment and 24 completed the follow-up measure. The results suggest that self-efficacy and depression, measured at baseline, are good predictors of 1- and 2-month outcomes, whereas depression and life stress, measured after 2 months of treatment, are good predictors of 4-month outcomes. In the strongest of these models, baseline scores of client self-efficacy and depressed affect explained as much as 48.7% of the variance in gambling behaviors 2 months later. PMID- 25112222 TI - Impulse control disorders are associated with multiple psychiatric symptoms in Parkinson's disease. AB - BACKGROUND: Impulse control disorders can have serious adverse consequences to the life of a patient with Parkinson's disease. Although impulse control disorders are common, a possible psychiatric comorbidity has not been fully characterized. OBJECTIVE: The aim of this study was to investigate the psychiatric symptoms exhibited by Parkinson's disease patients with impulse control disorders. METHODS: The study was conducted as a postal survey to patients in the registry of the Finnish Parkinson Association. A total of 290 Parkinson's disease patients were evaluated for impulse control disorders using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease. Psychiatric symptoms were systematically screened using the Symptom Checklist 90. RESULTS: We found that 108 of the evaluated patients had one or more impulse control disorders. Patients with impulse control disorders had markedly higher scores for symptoms of psychoticism (Bonferroni corrected p < 0.001), interpersonal sensitivity (p < 0.001), obsessive-compulsive disorder (p < 0.001), and depression (p = 0.01) when compared with patients without impulse control disorders. Impulse control disorders were shown to be independently associated with these symptoms. Patients with multiple impulse control disorders had higher scores for depression and obsessive-compulsive symptoms when compared with patients that exhibited only one impulse control disorder. COUNCLUSIONS: Our results confirm the previous observations that impulse control disorders in Parkinson's disease are linked with multiple psychiatric symptoms, including psychoticism, interpersonal sensitivity, obsessive-compulsive symptoms and depression. Clinicians treating these patients should acknowledge the concomitant psychiatric symptoms. PMID- 25112223 TI - Measuring stem cell dynamics in the human colon--where there's a wiggle, there's a way. AB - The last decade has seen huge improvements in our understanding of intestinal stem cell biology, with major advances arising from the ability to transgenically label, and thus identify, murine stem cells and their progeny. In the human, transgenic labelling is not an available option and stem cell dynamic observations have been based on rare hereditary mutations and polymorphisms. Somatic mitochondrial DNA mutations cause a histochemically detectable, but neutrally selected, change in cytochrome c oxidase (CCO) enzyme activity and when this occurs in an intestinal stem cell, it can be used as an effective clonal marker in both health and disease. The intestinal crypt is the functional unit of the gut. Daughter cells are 'born' in the stem cell niche at the crypt base and proliferate, differentiate, and then apoptose as they migrate along the vertical crypt axis over 5-7 days. This stereotypical architecture provides a historical record of cell dynamics, as the distance travelled along the crypt axis is proportional to the time since the daughter cell was born. By staining, identifying, and carefully reconstructing crypt maps from serial en face sections of partially mutated mtDNA crypts, clonal ribbon images can be generated. 'Wiggles' in the width of the clonal ribbon reflect mtDNA mutated stem cell expansion or contraction events and these biological observations are applied in mathematical models. This clever approach is able to infer temporal evolutionary dynamics from a static, single time point measurement, in both normal and familial adenomatous polyposis tissue. As we have seen in the mouse, the simple ability to identify stem cell progeny can lead to a vast expansion in our understanding of stem cell evolution. The use of these techniques to trace recent stem cell dynamics in the human colon makes some headway into the knowledge gap in our understanding of murine and human intestinal stem cell biology. (c) 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID- 25112224 TI - [Clearer labelling is required on tubes emitting ultraviolet C to prevent skin and eye lesions]. PMID- 25112225 TI - Detoxification of furfural in Corynebacterium glutamicum under aerobic and anaerobic conditions. AB - The toxic fermentation inhibitors in lignocellulosic hydrolysates raise serious problems for the microbial production of fuels and chemicals. Furfural is considered to be one of the most toxic compounds among these inhibitors. Here, we describe the detoxification of furfural in Corynebacterium glutamicum ATCC13032 under both aerobic and anaerobic conditions. Under aerobic culture conditions, furfuryl alcohol and 2-furoic acid were produced as detoxification products of furfural. The ratio of the products varied depending on the initial furfural concentration. Neither furfuryl alcohol nor 2-furoic acid showed any toxic effect on cell growth, and both compounds were determined to be the end products of furfural degradation. Interestingly, unlike under aerobic conditions, most of the furfural was converted to furfuryl alcohol under anaerobic conditions, without affecting the glucose consumption rate. Both the NADH/NAD(+) and NADPH/NADP(+) ratio decreased in the accordance with furfural concentration under both aerobic and anaerobic conditions. These results indicate the presence of a single or multiple endogenous enzymes with broad and high affinity for furfural and co factors in C. glutamicum ATCC13032. PMID- 25112226 TI - Engineering color variants of green fluorescent protein (GFP) for thermostability, pH-sensitivity, and improved folding kinetics. AB - A number of studies have been conducted to improve chromophore maturation, folding kinetics, thermostability, and other traits of green fluorescent protein (GFP). However, no specific work aimed at improving the thermostability of the yellow fluorescent protein (YFP) and of the pH-sensitive, yet thermostable color variants of GFP has so far been done. The protein variants reported in this study were improved through rational multiple site-directed mutagenesis of GFP (ASV) by introducing up to ten point mutations including the mutations near and at the chromophore region. Therefore, we report the development and characterization of fast folder and thermo-tolerant green variant (FF-GFP), and a fast folder thermostable yellow fluorescent protein (FFTS-YFP) endowed with remarkably improved thermostability and folding kinetics. We demonstrate that the fluorescence intensity of this yellow variant is not affected by heating at 75 degrees C. Moreover, we have developed a pH-unresponsive cyan variant AcS-CFP, which has potential use as part of in vivo imaging irrespective of intracellular pH. The combined improved properties make these fluorescent variants ideal tools to study protein expression and function under different pH environments, in mesophiles and thermophiles. Furthermore, coupling of the FFTS-YFP and AcS-CFP could potentially serve as an ideal tool to perform functional analysis of live cells by multicolor labeling. PMID- 25112227 TI - Surgical treatment of prolactinomas: cons. AB - Prolactinomas account for approximately 40 % of all pituitary adenomas. Over 95 % of prolactinomas are microadenomas (< 10 mm diameter). Treatment is indicated to correct hypogonadism, restore other hormonal deficits, and alleviate local mass effects. Dopamine agonists (DA) are highly effective in achieving these goals and are well-tolerated. The vast majority of prolactinomas will respond to conventional doses of cabergoline (<=2 mg/week) that do not carry an increased risk of cardiac valvular abnormalities. DA therapy may be successful withdrawn in a subset of patients and thus is not necessarily a lifelong commitment. Although transsphenoidal surgery (TSS) is an option for prolactinoma treatment, it is less effective than medical management, carries considerably more risk, and is more expensive. The benefit/risk ratio for DA therapy compared to TSS actually becomes increasingly more favorable as tumor size increases. Therefore DA should remain the clear treatment of choice for essentially all patients with prolactinomas, reserving TSS as a second-line option for the very small number of patients that do not tolerate or are completely resistant to DA therapy. PMID- 25112228 TI - Treatment of hyperprolactinemia in post-menopausal women: pros. AB - The incidence of hyperprolactinemia in women peaks during the 3rd-4th decade and then greatly decreases after the menopause. Apart from the effects on the hypothalamic-pituitary-gonadal axis, prolactin can act directly on bone metabolism. Hyperprolactinemia is a recognized cause of secondary osteoporosis, and treatment with dopamine agonists can lead to improved BMD. Moreover, hyperprolactinemia has been linked to weight gain and insulin resistance, which can be ameliorated following medical treatment. Although relatively rare, prolactinomas can be observed in post-menopausal women and are frequently large and invasive; dopamine agonists appear to be as effective in these patients as in younger women to induce reduction of prolactin levels and tumour shrinkage. Here, we review data potentially favouring medical treatment with dopamine agonists in post-menopausal women diagnosed with hyperprolactinemia. PMID- 25112229 TI - Interventions to reduce inappropriate prescribing of antipsychotic medications in people with dementia resident in care homes: a systematic review. AB - BACKGROUND: Antipsychotic medications are commonly used to manage the behavioral and psychological symptoms of dementia. Several large studies have demonstrated an association between treatment with antipsychotics and increased morbidity and mortality in people with dementia. AIMS: To assess the effectiveness of interventions used to reduce inappropriate prescribing of antipsychotics to the elderly with dementia in residential care. METHOD: Systematic searches were conducted in 12 electronic databases. Reference lists of all included studies and forward citation searching using Web of Science were also conducted. All quantitative studies with a comparative research design and studies in which recognized methods of qualitative data collection were used were included. Articles were screened for inclusion independently by 2 reviewers. Data extraction and quality appraisal were performed by 1 reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. RESULTS: Twenty-two quantitative studies (reported in 23 articles) were included evaluating the effectiveness of educational programs (n = 11), in-reach services (n = 2), medication review (n = 4), and multicomponent interventions (n = 5). No qualitative studies meeting our inclusion criteria were identified. Eleven studies were randomized or controlled in design; the remainder were uncontrolled before and after studies. Beneficial effects were seen in 9 of the 11 studies with the most robust study design with reductions in antipsychotic prescribing levels of between 12% and 20%. Little empirical information was provided on the sustainability of interventions. CONCLUSION: Interventions to reduce inappropriate prescribing of antipsychotic medications to people with dementia resident in care homes may be effective in the short term, but longer more robust studies are needed. For prescribing levels to be reduced in the long term, the culture and nature of care settings and the availability and feasibility of nondrug alternatives needs to be addressed. PMID- 25112230 TI - Low serum selenium level is associated with low muscle mass in the community dwelling elderly. AB - OBJECTIVES: Elderly persons with low muscle mass (LMM) or sarcopenia are prone to frailty and functional decline. This study aimed to investigate the relationship between serum selenium level and skeletal muscle mass in community-dwelling elderly. DESIGN: Cross-sectional observational study. SETTING AND PARTICIPANTS: A total of 327 elderly Taipei citizens (mean age 71.5 +/- 4.7 years) were recruited from the community. MEASUREMENTS: Skeletal muscle mass was measured by bioelectrical impedance analysis. LMM was defined by low skeletal muscle index (SMI: muscle mass (kg)/[height (m)](2)). All participants were further divided into quartiles by serum selenium level and the risk for LMM among these quartiles was examined using multivariate logistic regression analyses. Estimated serum selenium levels for the LMM group vs the normal group and estimated SMI in the quartiles of serum selenium were computed by least square method in linear regression models. RESULTS: The estimated mean (+/-standard deviation) of serum selenium level was significantly lower in the LMM group compared with the normal group after adjusting for confounders (1.01 +/- 0.03 MUmol/L vs 1.14 +/- 0.02 MUmol/L, P < .001). After adjusting for age, sex, lifestyle, and physical and metabolic factors, the odds ratios (95% confidence interval, P value) of LMM in the bottom, second, and third selenium quartile groups were 4.62 (95% CI 2.11 10.10, P < .001), 2.30 (95% CI 1.05-5.03, P < .05) and 1.51 (95% CI 0.66-3.46, P = .327), respectively, compared with the top quartile group of serum selenium level. The least square mean of SMI increased with the quartiles of serum selenium (P < .001). CONCLUSIONS: This is the first study to demonstrate that low serum selenium is independently associated with low muscle mass in the elderly. The causality and underlying mechanism between selenium and low muscle mass or sarcopenia warrant further research. PMID- 25112231 TI - Obesity: cerebral damage in obesity-associated metabolic syndrome. AB - The prevalence of the metabolic syndrome has increased in tandem with that of obesity. The metabolic syndrome is associated with structural and functional cerebral damage. A new study confirms the association between the metabolic syndrome and reduced brain volume in the absence of diabetes mellitus. Here, we highlight how vascular dysfunction potentially contributes to this brain damage. PMID- 25112232 TI - Biomarkers: Sclerostin levels linked to CKD outcomes. PMID- 25112233 TI - Diabetes: Protective role of autophagy in pancreatic beta cells. PMID- 25112234 TI - Diabetes: insulin pump therapy for type 2 diabetes mellitus. AB - The evidence base for the efficacy of insulin pump therapy in type 2 diabetes mellitus (T2DM) has been inconsistent to date. However, a recent large-scale randomized controlled trial comparing pump treatment with multiple daily insulin injections in patients with poorly controlled T2DM has shown substantial improvement in glycaemic control with pump therapy. PMID- 25112236 TI - Streaming potential and electroviscous effects in soft nanochannels: towards designing more efficient nanofluidic electrochemomechanical energy converters. AB - In this paper we provide analytical solutions for the streaming potential and electroviscous effects in soft nanochannels. The analysis is based on the solution of the linearized Poisson-Boltzmann equation, valid for small electrostatic potentials. We identify the important dimensionless parameters that dictate these two effects. Results are provided for a large range of electric double layer (EDL) thickness values, spanning from the case of very thin to very large overlapped EDL thicknesses. We compare the results with those of a rigid nanochannel, having zeta potential equal to the electrostatic potential at the solid-polyelectrolyte interface of the soft nanochannels. For the soft nanochannel, the streaming potential varies very weakly with the EDL thickness and can be substantially larger than that corresponding to the rigid nanochannel. The electroviscous effects for the soft nanochannel, unlike the rigid nanochannel, virtually always exhibit a monotonic decrease with the EDL thickness, and for certain parameter ranges can be several times larger than that for a rigid nanochannel. Most importantly, for the soft nanochannels the electrochemomechanical energy conversion, associated with the generation of streaming potential, is found to be highly efficient, with the efficiency being several times higher than that of a rigid nanochannel. PMID- 25112237 TI - Australian marsh beetles (Coleoptera: Scirtidae). 6. Genera Calvarium Pic, Papuacyphon Zwick, and Ypsiloncyphon Klausnitzer. AB - The genus Calvarium Pic, 1918 is for the first time recorded from Australia. Six new Australian species are named and described. Calvarium australiense n. sp. and C. superbum n. sp. from the Northern Territory are typical representatives of the genus. A new subgenus, Calvariellum n. subgen., is proposed for four species from NE Queensland which share general body structure with other Calvarium species but have different, less derived male genitalia: Calvarium (Calvariellum) bellendenker n. sp., C. (Calvariellum) cochlearifer n. sp., C. (Calvariellum) hamifer n. sp., and C. (Calvariellum) lancifer n. sp. Papuacyphon darwini n. sp. is described from SW Australia. The genus was previously known only from Papua New Guinea. Species Group 3 of the genus Ypsiloncyphon Klausnitzer, 2009 is first recorded from Australia. It is endemic to the Australasian region. The Australian species Y. angustus n. sp., Y. brevis n. sp., Y. katherinae n. sp., Y. longus n. sp., Y. pusillus n. sp., Y. velatus n. sp., and Y. virgulifer n. sp. are described, the New Guinean species Y. micans (Klausnitzer, 1973) (= Cyphon paramicans Klausnitzer, 1973, n. syn.), Y. mutilatus n. sp., Y. ruficollis n. sp., and Y. rugosus n. sp. are described or redescribed from types, respectively. Three Australian species known only in the female sex are described under informal designations. PMID- 25112238 TI - Synopsis of Oryssomini Gordon (Coleoptera: Coccinellidae) from the Neotropical region with new species of Oryssomus Mulsant, Pseudoryssomus Gordon and Gordonoryssomus Almeida & Lima. AB - Six new species of Oryssomus are described: O. calix sp. nov., O. guillermo sp. nov., O. guyanensis sp. nov. and O. rhombus sp. nov., from French Guiana; and O. paschoali sp. nov. and O. rogeri sp. nov., from Brazil. Four new species of Pseudoryssomus are described: P. brulei sp. nov., P. crucifer sp. nov., P. triangulus sp. nov., from French Guiana; and P. rufomarginatus sp. nov., from Trinidad and Tobago. Three new species of Gordonoryssomus are described: G. mirnae sp. nov., from Peru, G. everardoi sp. nov. and G. limeirai sp. nov., from Brazil. The new species are placed within the South American classification of Gordon (1974) and Almeida & Lima (1995). Keys to genera and species of Oryssomus, Pseudoryssomus and Gordonoryssomus are included. Distribution maps and a checklist of the known species of Oryssomini are provided. PMID- 25112239 TI - An annotated checklist of scale insects (Hemiptera: Coccoidea) of Saint Lucia, Lesser Antilles . AB - An annotated list of 83 scale insect species (Hemiptera: Sterorrhyncha: Coccoidea) recorded from Saint Lucia is presented, based on data gathered from UK quarantine interceptions, samples collected in an urban coastal habitat in the North West of the Island in 2013, and published records. Thirty-three species (40%) are recorded for the first time for the country, including Dysmicoccus joannesiae (Costa Lima), a South American mealybug, and Poliaspoides formosana (Takahashi), an Asian armoured scale insect pest of bamboo, which are new for the Caribbean region. The economic, environmental and social impacts caused by introduced exotic species of scale insect are discussed. Two predatory midges Diadiplosis ?coccidivora (Felt) and Diadiplosis multifila (Felt) (Diptera: Cecidomyiidae) are recorded for the first time from Saint Lucia. The latter species was observed causing 90% mortality of a large infestation of passion vine mealybug Planococcus minor (Maskell) on soursop fruit. PMID- 25112235 TI - Gynaecomastia--pathophysiology, diagnosis and treatment. AB - Gynaecomastia (enlargement of the male breast tissue) is a common finding in the general population. Most cases of gynaecomastia are benign and of cosmetic, rather than clinical, importance. However, the condition might cause local pain and tenderness, could occasionally be the result of a serious underlying illness or a medication, or be inherited. Breast cancer in men is much less common than benign gynaecomastia, and the two conditions can usually be distinguished by a careful physical examination. Estrogens are known to stimulate the growth of breast tissue, whereas androgens inhibit it; most cases of gynaecomastia result from deficient androgen action or excessive estrogen action in the breast tissue. In some cases, such as pubertal gynaecomastia, the breast enlargement resolves spontaneously. In other situations, more active treatment might be required to correct an underlying condition (such as hyperthyroidism or a benign Leydig cell tumour of the testis) or medications that could cause breast enlargement (such as spironolactone) might need to be discontinued. For men with hypogonadism, administration of androgens might be helpful, as might antiestrogen therapy in men with endogenous overproduction of estrogens. Surgery to remove the enlarged breast tissue might be necessary when gynaecomastia does not resolve spontaneously or with medical therapy. PMID- 25112241 TI - Cleridae (Insecta: Coleoptera) type collection at National Forest Insect Collection (NFIC), Forest Research Institute, Dehradun (India). AB - Clerids are small predacious beetles (Coleoptera) that belong to the family Cleridae. In the National Forest Insect Collection (NFIC) Cleridae is represented by 31 authentically identified specimens including types of 27 species. The type material of Cleridae, deposited in the NFIC, Forest Research Institute, Dehradun (India), is listed and illustrated with digital automontage photographs. A list of 27 type species of Cleridae, 13 holotypes and 14 paratypes with information on species names, reference of the original publication, all available information on labels of types (country, locality, date of collection, collector name, etc) along with colored photographs of types and the labels that are attached to them, taken with Auto-montage 3-D imaging system, is provided. PMID- 25112240 TI - Two new genera and five new species of Teloganodidae (Ephemeroptera) from South India. AB - Two new genera and five new species of teloganodid mayflies (Ephemeroptera: Pannota: Ephemerelloidea) are described based on larvae from south India: Janohyphella indica, n. gen., n. sp., Indoganodes jobini, n. gen., n. sp., Teloganodes sartorii, n. sp., Dudgeodes palnius, n. sp., and Derlethina tamiraparaniae, n. sp. Janohyphella, n. gen., is distinguished from the larvae of other teloganodid genera by having a combination of three subequal caudal filaments, lamellate gills on abdominal segments II through V and posterolateral processes well-developed on abdominal segments II through IX, except III. Indoganodes, n. gen., is distinguished from the larvae of other teloganodid genera by having three subequal caudal filaments, lamellate gills on abdominal segments II through VI, posterolateral projections weakly developed on abdominal segments I through V, but distinct on segments VI through IX. Our new species of Dudgeodes Sartori, 2008 and Derlethina Sartori, 2008 represent the first discoveries of these genera outside Southeast Asia, with the latter genus previously considered endemic to Borneo. Emendations to the larval species key of known Oriental Teloganodidae are provided. We hypothesize that the occurrence of the new taxa in southern India is a result of the tectonic events associated with the split-up of Gondwana. This illustrates the profound biogeographical significance of how vicariance led to the establishment of some distinct oriental lineages initially on the rafting Indian Deccan Plate, which might have triggered dispersal events for subsequent species diversification in Southeast Asia. PMID- 25112242 TI - A new species of Hetereleotris (Perciformes: Gobiidae) from Farasan Island (Red Sea). AB - A new species of the genus Hetereleotris is described from Farasan Island, Saudi Arabia, Red Sea, on the basis of a single specimen. Hetereleotris dorsovittata sp. nov is unique among the known sixteen species of Hetereleotris, except for H. diademata and H. psammophila, in the combination of the absence of head canals and lack of squamation. The low count of pectoral-fin rays (14) is only overlap with H. psammophila (14 or 15), whereas all other Hetereleotris species have a higher number of pectoral-fin rays. The new species differs from H. psammophila in having more soft rays in the dorsal and anal fins, by the arrangement of papillae in the preoperculo-mandibular row i and by coloration. The single specimen was collected in the large lagoon at the base of an isolated small coral patch at a depth of 1m. PMID- 25112243 TI - New data on the genus Micromus Rambur, 1842 from China (Neuroptera, Hemerobiidae), with a key to Chinese species. AB - A review of the genus Micromus Rambur from China is presented. A new species, Micromus setulosus sp. nov., which was found in Ningxia province, is described. The male of Micromus pallidius (Yang, 1987) and the female of Micromus perelegans Tjeder, 1936 are described for the first time in China. Keys to the adult males and females of the Micromus from China are also given. PMID- 25112244 TI - Rumen ciliates in the African (Cape) buffalo (Syncerus caffer caffer) living in the vicinity of the Orpen Gate entrance into Kruger National Park, South Africa. AB - Samples of rumen contents were obtained from 10 African (Cape) buffalo living in the vicinity of the Orpen Gate entrance into Kruger National Park in South Africa. Total number of ciliate protozoa per animal ranged from 3.15 to 23.25 x 103. Forty three different species and forms were observed, of which 35 are a new host record. The total number of species and forms per animal varied from 10 to 17. Eudiplodinium maggii occurred in all 10 animals, followed by Dasytricha ruminantium in nine animals. Diplodinium posterovesiculatum, Eudiplodinium magnodentatum and Ostracodinium mammosum were present in seven animals with all other species and forms occurring in five or less animals. PMID- 25112245 TI - The first species of the spider genus Episinus in Colombia (Araneae, Theridiidae). PMID- 25112246 TI - Revision of the systematics of the cardinalfishes (Percomorpha: Apogonidae) based on molecular analyses and comparative reevaluation of morphological characters. AB - Molecular analyses were conducted based on 120 of the estimated 358 species of the family Apogonidae with 33 of 40 genera and subgenera, using three gobioids and one kurtid as collective outgroups. Species of Amioides, Apogon, Apogonichthyoides, Apogonichthys, Archamia, Astrapogon, Brephamia, Cercamia, Cheilodipterus, Fibramia n. gen., Foa, Fowleria, Glossamia, Gymnapogon, Jaydia, Lachneratus, Nectamia, Ostorhinchus, Paroncheilus, Phaeoptyx, Pristiapogon, Pristicon, Pseudamia, Pterapogon, Rhabdamia, Siphamia, Sphaeramia, Taeniamia, Verulux, Vincentia, Yarica, Zapogon and Zoramia were present in the molecular analyses; species of Bentuviaichthys, Holapogon, Lepidamia, Neamia, Paxton, Pseudamiops and Quinca were absent from the analyses. Maximum-likelihood (ML), Bayesian (BA), and Maximum parsimony (MP) analyses based on two mitochondrial (12S rRNA-tRNAVal-16S rRNA, ca. 1500 bp; COI, ca. 1500 bp) and two nuclear DNA (RAG1, ca. 1300 bp; ENC1, ca. 800 bp) fragments reproduced two basal clades within the monophyletic family: one including a single species, Amioides polyacanthus, and the other comprising species of Pseudamia. All the other apogonid species formed a large well-established monophyletic group, in which almost identical 12 major clades were reproduced, with phylogenetic positions of four species (Glossamia aprion, Ostorhinchus margaritophorus, Pterapogon kauderni, and Vincentia novaehollandiae) left unsettled. Apogon sensu lato and recent Ostorhinchus (excepting O. margaritophorus) were divided into six and three major clades, respectively. Each of the recognized clades in the family was then evaluated for morphological characters to identify synapomorphies. Based on the results of the molecular analyses and the reevaluation of morphological characters, four subfamilies were proposed within the family: Apogoninae (including most of the species in the family), Amioidinae new subfamily (including Amioides, and based on morphology, Holapogon), Paxtoninae new subfamily (including Paxton, based only on morphology) and Pseudamiinae (including Pseudamia). Within the largest subfamily Apogoninae, twelve new tribes were proposed based on the 12 molecular clades and associated morphology: Apogonichthyini, Apogonini (mainly including species of Apogon sensu stricto), Archamiini, Cheilodipterini, Gymnapogonini, Ostorhinchini (including striped species of recent Ostorhinchus), Pristiapogonini, Rhabdamiini, Sphaeramiini (mainly including barred species of traditional Ostorhinchus, such as Apogonichthyoides, Jaydia and Nectamia), Siphamiini, Veruluxini, and Zoramiini. Two additional tribes are proposed based only on morphology: Glossamiini and Lepidamiini. For each of the 14 tribes, morphological characters were described. One new genus, Fibramia, type species Apogon thermalis, recently in Ostorhinchus, was described supported by morphology and molecular trees. A key to all genera is provided and all valid and uncertain status species are allocated to tribes and genera. PMID- 25112247 TI - Additions to the Nepticulidae (Lepidoptera) of East Asia, with descriptions of three new species from Primorskiy Kray. AB - Stigmella multispicata Rociene & Stonis, sp. nov., S. sexcornuta Rociene & Stonis, sp. nov., and Ectoedemia paraortiva Rociene & Stonis, sp. nov. are described from Primorskiy Kray (Russian Far East). The new species are illustrated with photographs and drawings of the adults and genitalia. Stigmella thuringiaca (Petry), a species previously known only from West Palaearctic, is here newly recorded in East Asia. The male genitalia of the little known Stigmella gimmonella (Matsumura) are illustrated for the first time with photographs; the male genital morphology of two other species, S. tranocrossa Kemperman & Wilkinson and Ectoedemia philipi Puplesis, is updated and newly documented. A chart of chorological composition of the Nepticulidae currently known in East Asia is provided. PMID- 25112248 TI - First evidence of cynipids from the Oceanian Region: the description of Lithonecrus papuanus a new genus and species of cynipid inquiline from Papua New Guinea (Hymenoptera: Cynipidae, Synergini). AB - Lithonecrus papuanus Nieves-Aldrey & Butterill, a new genus and species of inquiline oak gall wasps (Hymenoptera: Cynipidae: Synergini), is described from material reared from galls on Lithocarpus celebicus (Miq.) Rehd., collected in Papua New Guinea. The new genus and species is the first record of a cynipid from Papua New Guinea and the whole Oceanian biogeographic region, and represents the easternmost oriental record of a cynipid wasp (Hymenoptera: Cynipidae). The new genus is similar to Saphonecrus Dalla Torre & Kieffer, and to the recently described Lithosaphonecrus Tang, Melika & Bozso, but differs from these genera in several important diagnostic characters. Taxonomic affinities and differences with related genera and species and biogeographical implications are discussed. PMID- 25112249 TI - Pethia longicauda, a new species of barb (Teleostei: Cyprinidae) from the northern Western Ghats, India. AB - Pethia longicauda, a new cyprinid fish, is described from Hiranyakeshi River, Krishna drainage, Maharashtra, India. It can be distinguished from congeners based on a combination of characters including: a long caudal peduncle, incomplete lateral line, absence of barbels, upper lip thick and fleshy, distinct lateral fold on snout, 22-24 scales in lateral series, 5-6 lateral-line pored scales, nine predorsal scales, 9-10 prepelvic scales, 15-17 preanal scales, 1/23/1/31/2 transverse scales, 11-15 pairs of serrae on the distal half of the last unbranched dorsal-fin ray, 11-13 branched pectoral fin rays, 4+26 total vertebrae, 4+5 predorsal vertebrae, 4+13 abdominal and 13 caudal vertebrae, body iridescent silver in color with a black humeral spot, two black blotches on caudal peduncle and dorsal fin usually without any color bands or blotches but in breeding males with two rows of minute, indistinct black spots. PMID- 25112250 TI - A taxonomic revision of boas (Serpentes: Boidae). PMID- 25112251 TI - Two new Aprostocetus species (Hymenoptera: Eulophidae: Tetrastichinae), fortuitous parasitoids of invasive eulophid gall inducers (Tetrastichinae) on Eucalyptus and Erythrina. AB - Two closely related new species of Aprostocetus Westwood (Hymenoptera: Eulophidae: Tetrastichinae) are described as fortuitous parasitoids of invasive gall inducers in two other genera of Tetrastichinae, Leptocybe Fisher & LaSalle and Quadrastichus Girault. Aprostocetus causalis La Salle & Wu is a parasitoid of Leptocybe invasa Fisher & La Salle on Eucalyptus spp. (Myrtaceae) in China and Thailand, and A. felix La Salle, Yang & Lin is a parasitoid of Quadrastichus erythrinae Kim on Erythrina spp. (Fabaceae) in Taiwan. Epitetrastichus nigriventris Girault, 1913 is removed from synonymy from Aprostocetus gala (Walker), and treated as the valid species A. nigriventris (Girault). PMID- 25112252 TI - The genus Nyctiophylax Brauer in China (Trichoptera, Polycentropodidae). AB - Currently, 8 species of the genus Nyctiophylax Brauer are known from China. Examination of material collected from Guangdong, Guangxi, Jiangxi and Sichuan Provinces during 2004-2005 has revealed 4 new species and 2 new records of this genus, bringing the number of Chinese Nyctiophylax species to 14. Newly described species include: Nyctiophylax (Paranyctiophylax) crinalis n. sp., N. (P.) dactylatus n. sp., N. (P.) orbicularis n. sp., and N. (P.) macrorrhinus n. sp. Nyctiophylax (Paranyctiophylax) sagax Mey and N. (N.) amphonion Malicky & Chantaramongkol are newly recorded for the Chinese fauna, which are re illustrated and re-described for clear comparisons. The additional collection sites for the previously described species are provided. PMID- 25112253 TI - Two new species of Syrphidae (Diptera) from Chukotka (Northern Russian Far East). AB - Two new species, Platycheirus beringiensis sp. n. and Cheilosia chukotana sp. n., are described from Chukotka (northern part of Russian Far East). The new Platycheirus is close to Platycheirus immarginatus (Zetterstedt), but differing by the following characters: fore tibia with a black stripe on posterior side; mid-femur without fine black curved hairs directed to the base of the femur; mid tibia without long anteroventral hairs; abdomen black with fine brownish lustre on tergites. The new Cheilosia species is close to Ch. semifasciata Becker, but differs by its characteristic sharply raised central knob, and by lack of transversal stripe and indentation in anterior third of frons. PMID- 25112254 TI - Two new species of quill mites of the family Syringophilidae (Acariformes: Cheyletoidea) associated with treronine doves (Columbiformes: Columbidae: Treroninae). AB - Two new species of quill mites (Acariformes: Syringophilidae) associated with doves of the subfamily Treroninae (Columbiformes: Columbidae) from the Oceanian realm are described: Gunabopicobia masalaje sp. nov. from six avian host species, Ptilinopus iozonus Gray (type host) Ducula pistrinaria (Bonaparte), D. rosacea (Temminck), D. rufigaster (Quoy and Gaimard), D. spilorrhoa (Gray), D. luctuosa (Temminck), and Peristerophila lature sp. nov. also from six host species Ducula luctuosa (type host ), D. spilorrhoa, Ptilinopus jambu Gmelin, P. melanospilus Salvadori, P. porphyreus Temminck, P. regina Swainson. Additionally, Treron waalia (Meyer) is noted as a new host species for Meitingsunes columbicus Glowska and Skoracki, 2010. PMID- 25112255 TI - Species-richness in the Oriental fungus-feeding thrips of the genus Azaleothrips (Thysanoptera, Phlaeothripidae). AB - Azaleothrips, a phlaeothripine genus of fungus-feeding species, is presumably endemic to the Oriental Region between India and Japan. Although only 10 species have been known in this genus until now, a total of 35 species is recorded here, of which 26 are newly described: from Indonesia--A. bali sp.n., A. bulelengi sp.n., A. dentatus sp.n., A. dorsalis sp.n., A. floresi sp.n., A. inflavus sp.n., A. simulans sp.n., A. sulawesicus sp.n., from the Philippines--A. apoensis sp.n., A. bifidius sp.n., A. luzonensis sp.n., A. mindanaoensis sp.n., A. philippinensis sp.n., from Taiwan--A. atayal sp.n., A. formosae sp.n., A. taiwanus sp.n., from Thailand--A. flavicollis sp.n., A. phuketanus sp.n., A. pulcher sp.n., A. toshifumii sp.n., from Vietnam--A. laocai sp.n., A. vietnamensis sp.n., from W. Malaysia--A. malaya sp.n., A. reticulatus sp.n., A. richardi sp.n., A. templeri sp.n. In addition A. magnus Chen, described from Taiwan, is newly synonymized with A. moundi. Azaleothrips laevigatus, described from southern Japan, is newly recorded more widely in Southeast Asia. A key to 33 species is provided, but A. bhattii and A. lineus cannot be recognized because of the poor information in the original descriptions. PMID- 25112256 TI - A new diminutive frog species of Adelophryne (Amphibia: Anura: Eleutherodactylidae) from the Atlantic Forest, southeastern Brazil. AB - The genus Adelophryne is composed of diminutive frogs occurring in northern Amazonia and the Atlantic Forest. Herein we describe a new species of Adelophryne found in the leaf litter of primary and secondary forests in the mountainous region of Espirito Santo state, southeastern Brazil. The new species is characterized by its small body size, two phalanges in the finger IV, and a glandular ridge line that runs from the posterior part of eye to the insertion of the forelimb. This species is sensitive to edge effect and conversion of native forest into coffee and Eucalyptus plantations and may be listed as Endangered (EN) under B1ab(iii) criteria of the IUCN Red List. PMID- 25112257 TI - New species of Pseudonannolene Silvestri, 1895 from Brazilian limestone caves with comments on the potential distribution of the genus in South America (Spirostreptida: Pseudonannolenidae). AB - Ten new species of Pseudonannolene Silvestri, 1895 are described from Brazilian limestone caves. The species are separated by the morphology of their gonopods and the processes of the first pair of legs of males. A pictorial identification key for the cave-dwelling species from Brazil is provided, besides comments on the distribution of the genus with a potential distribution map of Pseudonannolene and Epinannolene in South and Central America. PMID- 25112258 TI - A re-description of rare alpheid shrimp Amphibetaeus jousseaumei (Coutiere, 1896) and escription of a new species of the genus Athanopsis Coutiere, 1897(Crustacea: Decapoda: Alpheidae) from Iranian coast of the Persian Gulf. AB - A new record of rare alpheid shrimp Amphibetaeus jousseaumei (Coutiere, 1896) (Decapoda: Caridea: Alpheidae) is presented based on material collected from Qeshm Island, Iran, the Persian Gulf. This is the first record of the species for the Iranian waters as well as the second record and re-description of A. jousseaumei from its original description given by Coutiere (1896). Besides, a new alpheid shrimp species Athanopsis tarahomii sp. nov. is described from the same locality. The new species can be clearly separated from all remaining species of the genus Athanopsis by deep rostrum curved downward and the presence of well marked blunt extra-cornea tooth on carapace. PMID- 25112259 TI - Taxonomic utility of niche models in validating species concepts: A case study in Anthophora (Heliophila) (Hymenoptera: Apidae). AB - Taxonomy has far-reaching effects throughout biology, and incorrect taxonomy can be detrimental in many ways. Polymorphic species complexes, many of which exist in the bee genus Anthophora Latreille, lend themselves to such difficulties. This study employs environmental niche mapping (ENM) and traditional morphological analyses to investigate the validity of the subjective synonymy of Anthophora (Heliophila) curta Provancher with the senior synonym A. squammulosa Dours. Eleven of fifty morphological characters consistently differentiate the two putative species, with an additional five characters sometimes separating them. Additionally, based on over 1000 georeferenced museum specimens, the geographic ranges of the two taxa do not overlap. The two entities also react differently to the bioclimatic variables based on correlation analysis. We further tested the two-species hypothesis by constructing ENMs with informative bioclimatic variables associated with locality records. Their modelled distributions overlapped less than 1%, suggesting discrete environmental boundaries. The variables which contributed most to each species' model also differed. These differences are explored in relation to their habitats. The combined morphological and biogeographic analysis indicates that A. curta and A. squammulosa are distinct species. Based on the accumulated evidence the synonymy is formally rejected and A. curta is recognized as a valid species. Five additional taxa (A. bispinosa Cockerell, A. franciscana Cockerell, A. usticauda Cockerell, A. u. cinerior Cockerell, A. zamoranella Cockerell) are newly synonymized with A. squammulosa and Anthophora curta var. melanops Cockerell is newly synonymized with A. curta. Implications outside of taxonomy are discussed. PMID- 25112260 TI - Description of Ektaphelenchoides fuchsi n. sp. (Nematoda: Ektaphelenchinae) from western Iran. AB - Ektaphelenchoides fuchsi n. sp., recovered from a soil sample around the rhizosphere of Cucurbita maxima in western Iran, is described and illustrated based on morphological and molecular characters. The new species is characterized by its body length of 529-712 um, continuous lip region, lateral fields with three incisures, total stylet length of 14-18 um with rounded basal knobs, excretory pore 70-84 um and hemizonid 87-96 um from the anterior end, post uterine sac short, 6-9 um long in female and tail conoid with long filiform terminus in male. Based on morphological and molecular characters, the new species is close to E. kelardashtensis, E. attenuata, and E. musae. It differs from the closest species E. kelardashtensis by its longer sylet (14-18 vs 13-16 um) and stylet with basal knobs vs not, longer post uterine sac (6-9 vs 3-6 um), more posterior position of excretory pore and hemizonid (70-84 vs 55-66 and 87-96 vs 67-78 um, respectively), and longer spicules (12-13 vs 8-10 um). Comparisons with other species of Ektaphelenchoides are also discussed. Molecular analyses were performed based on 631 bp of the partial ribosomal RNA large subunit gene (D2/D3 of LSU) and showed that E. fuchsi n. sp. is unique when compared with other species of the genus for which sequences of that region are available. PMID- 25112261 TI - Laomenes albonigrus sp. nov., (Crustacea: Decapoda; Pontoniinae) from Ashmore Reef, Western Australia. AB - One specimen of an un-described species of pontoniine shrimp of the genus Laomenes Clark, 1919, Laomenes albonigrus sp. nov., was collected from a crinoid host from Ashmore Reef, Western Australia, and is now described and illustrated. PMID- 25112262 TI - Grammoplites vittatus (Valenciennes), (Scorpaeniformes, Platycephalidae), removed from synonymy with Grammoplites scaber (Linnaeus). AB - Grammoplites vittatus (Valenciennes), often previously overlooked by authors or regarded as a junior synonym of G. scaber (Linnaeus), is shown here to be a valid species. It has more gill rakers (7-8) then G. scaber and G. knappi (usually 6) and a narrower interorbital width than G. scaber. A key to the species of Grammoplites Fowler is given. PMID- 25112263 TI - A phylogenetic analysis of the southern African gecko genus Afroedura Loveridge (Squamata: Gekkonidae), with the description of nine new species from Limpopo and Mpumalanga provinces of South Africa. AB - A molecular phylogeny of the largely rupicolous geckos of the gekkonid genus Afroedura is presented based on a combination of mitochondrial and nuclear gene sequence data. Previously recognized species groups are only partly recovered, with A. pondolia retrieved as very distantly related to the congeners to which it was previously considered allied. Afroedura hawequensis forms a monotypic group that is sister to all other species, which are allocated to the A. nivaria, A. transvaalica, A. africana, A. multiporis, A. marleyi, and A. langi groups. The taxonomic status of species occurring in the former Transvaal province of South Africa (now Limpopo and Mpumalanga provinces) is reviewed based on morphological and molecular evidence. Afroedura rupestris sp. nov. is described in the A. multiporis group, A. maripi sp. nov., A. pongola sp. nov., and A. rondavelica sp. nov., are described in the A. marleyi group, and A. broadleyi sp. nov., A. granitica sp. nov., A. leoloensis sp. nov., A. pienaari sp. nov., and A. waterbergensis sp. nov. are described in the A. langi group. In addition, A. haackei, A. namaquensis, and A. tirasensis, are all raised to specific status. The description of nine new species highlights Limpopo and Mpumalanga provinces as previously unrecognized centers of diversity for the genus Afroedura. A key to the species of Afroedura is provided. PMID- 25112264 TI - Revision of opeatocerata melander, 1928 (Diptera: empididae: empidinae). AB - The species of the Neotropical genus Opeatocerata Melander are revised to include 21 species, with fifteen species described as new: O. agudeloi sp. nov., O. ampullaria sp. nov., O. bare sp. nov., O. brasiliensis sp. nov., O. chaetohypandrialis sp. nov., O. cylindrophallus sp. nov., O. curvipenis sp. nov., O. hadrophallus sp. nov., O. megalophallus sp. nov., O. mourai sp. nov., O. nhamunda sp. nov., O. smithi sp. nov., O. spinipenis sp. nov., O. tanimboca sp. nov. and O. zuleideae sp. nov. All species are described and male and female genitalia illustrated. An identification key and the geographic distributions of the species are also presented. PMID- 25112265 TI - Plant mites of the Dominican Republic, with a description of a new species of Petrobia (Tetranychina) Wainstein, 1960 (Acari, Prostigmata, Tetranychidae) and a key to the species of this subgenus. AB - Fourteen mite species of plant-associated mites of the suborder Prostigmata are reported from the Dominican Republic. Four of these refer to new findings for the country, including Petrobia (Tetranychina) hispaniola n. sp. Sanchez & Flechtmann, described from specimens collected from leaves of Citrus sp. (Rutaceae) and Rosa sp. (Rosaceae). A key for the separation of the world species of Petrobia (Tetranychina) is presented. PMID- 25112266 TI - The genus Mytilina in China, with description of a new species (Rotifera: Monogononta: Mytilinidae). AB - During our study of biodiversity of Rotifera in PR China, as model taxon of freshwater Micrometazoa, we came across several records that warrant revision regarding species of genus Mytilina Bory de St. Vincent, 1826 (Rotifera, Monogonta, Mytilinidae). In addition to this review we describe a new species encountered during examination of freshwater habitats of Inner Mongolia, P.R.China. This new species, Mytilina wangi n. sp., appears to belong to the Mytilina mucronata - ventralis complex but differs from the known taxa in the group by its domed lorica and relatively short toes. We provide an annotated checklist of the Chinese representatives of the genus and discuss the species of the M. mucronata-ventralis group. We suggest treating M. brevispina (Ehrenberg, 1830) and M. ventralis (Ehrenberg, 1830)(synonym: M. macracantha (Gosse, 1886)) as separate species-level taxa rather than as two infrasubspecific variants of the same species, and argue that Mytilina trigona var. bispinosa Wang, 1961 is a misidentified M. acanthophora Hauer, 1938 rather than an infrasubspecific variant of M. trigona (Gosse, 1851). PMID- 25112267 TI - A new species of Hypoaspis Canestrini from Iran (Acari: Laelapidae), with a key to the species occurring in the Western Palaearctic Region. AB - Hypoaspis elegans sp. nov. was collected on adult female Oryctes elegans Prell. (Coleoptera: Scarabaeidae) in Bam, Kerman province, Iran. The new species is described and illustrated from adult females. Hypoaspis surii Khanjani et. al., 2013 is a junior synonym of Hypoaspis maryamae Joharchi & Halliday, 2011. A key to the Western Palaearctic species of Hypoaspis is presented. PMID- 25112268 TI - Description of Hylopanchax paucisquamatus (Cyprinodontiformes: Poeciliidae), a new lampeye species from the Odzala-Kokoua National Park, Republic of Congo. AB - A new deep-bodied Hylopanchax species is described from the northwestern Congo basin. Hylopanchax paucisquamatus, new species, was collected in the Odzala Kokoua National Park in the Likouala River drainage of the Republic of Congo. It differs from its congeners, including the deep-bodied H. leki and H. ndeko, by a unique combination of morphological characters, including low number of mid longitudinal and transverse scales, number of dorsal-fin rays, and position of dorsal-fin origin in relation to anal-fin. It is the only deep-bodied species currently known outside the Kasai River drainage. PMID- 25112269 TI - Ceriomicrodon petiolatus Hull, 1937 (Diptera, Syrphidae, Microdontinae): Redescription and new records. AB - The monotypic genus Ceriomicrodon Hull, 1937 was known in the current literature by a few specimens, all from Brazil but with records only for Mato Grosso and Roraima states. The only species of the genus is here redescribed including the description of the female and its terminalia, in addition to a preliminary description of the egg. Images of male and female genitalia and egg are provided. New Brazilian records for Amazonas, Maranhao and Rondonia and a brief diagnosis to distinguish that genus from other similar Microdontinae genera are presented. PMID- 25112270 TI - New and little known bees of the genus Colletes Latreille 1802 (Hymenoptera: Colletidae) from Central Asia. AB - In addition to a previously published study about Central Asian Colletes bees we here further report on nine rarely collected and little known species. Now 85 species of Colletes are known from this region with three of them recorded for the first time: C. asiaticus Kuhlmann 1999, C. iranicus Noskiewicz 1962 and C. succinctus (Linnaeus 1758). Colletes pseudomirabilis sp. nov. is described from Turkmenistan. PMID- 25112271 TI - One new species of the genus Alloteratura Hebard, 1922 (Orthoptera: Tettigoniidae: Meconematinae) from Yunnan, China. AB - The paper describes one new species of the genus Alloteratura Hebard, 1922 from Yunnan, China, i.e. Alloteratura quaternispina, sp. nov. PMID- 25112272 TI - Cross-cultural adaptation and reliability and validity of the Dutch Patient-Rated Tennis Elbow Evaluation (PRTEE-D). AB - BACKGROUND: Lateral Epicondylalgia (LE) is a common injury for which no reliable and valid measure exists to determine severity in the Dutch language. The Patient Rated Tennis Elbow Evaluation (PRTEE) is the first questionnaire specifically designed for LE but in English. The aim of this study was to translate into Dutch and cross-culturally adapt the PRTEE and determine reliability and validity of the PRTEE-D (Dutch version). METHODS: The PRTEE was cross-culturally adapted according to international guidelines. Participants (n = 122) were asked to fill out the PRTEE-D twice with a one week interval to assess test-retest reliability. Internal consistency of the PRTEE-D was determined by calculating Crohnbach's alphas for the questionnaire and subscales. Intraclass Correlation Coefficients (ICC) were calculated for the overall PRTEE-D score, pain and function subscale and individual questions to determine test-retest reliability. Additionally, the Disabilities for the Arm, Shoulder and Hand questionnaire (DASH) and Visual Analogue Scale (VAS) pain scores were obtained from 30 patients to assess construct validity; Spearman's correlation coefficients were calculated between the PRTEE-D (subscales) and DASH and VAS-pain scores. RESULTS: The PRTEE was successfully cross-culturally adapted into Dutch (PRTEE-D). Crohnbach's alpha for the first assessment of the PRTEE-D was 0.98; Crohnbach's alpha was 0.93 for the pain subscale and 0.97 for the function subscale. ICC for the PRTEE-D was 0.98; subscales also showed excellent ICC values (pain scale 0.97 and function scale 0.97). A significant moderate correlation exists between PRTEE-D and DASH (0.65) and PRTEE-D and VAS pain (0.68). CONCLUSION: The PRTEE was successfully cross culturally adapted and this study showed that the PRTEE-D is reliable and valid to obtain an indication of severity of LE. An easy-to-use instrument for practitioners is now available and this facilitates comparing Dutch and international research data. PMID- 25112273 TI - Decision support system for age-related macular degeneration using discrete wavelet transform. AB - Age-related macular degeneration (AMD) affects the central vision and subsequently may lead to visual loss in people over 60 years of age. There is no permanent cure for AMD, but early detection and successive treatment may improve the visual acuity. AMD is mainly classified into dry and wet type; however, dry AMD is more common in aging population. AMD is characterized by drusen, yellow pigmentation, and neovascularization. These lesions are examined through visual inspection of retinal fundus images by ophthalmologists. It is laborious, time consuming, and resource-intensive. Hence, in this study, we have proposed an automated AMD detection system using discrete wavelet transform (DWT) and feature ranking strategies. The first four-order statistical moments (mean, variance, skewness, and kurtosis), energy, entropy, and Gini index-based features are extracted from DWT coefficients. We have used five (t test, Kullback-Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance, receiver operating characteristics curve-based, and Wilcoxon) feature ranking strategies to identify optimal feature set. A set of supervised classifiers namely support vector machine (SVM), decision tree, [Formula: see text]-nearest neighbor ([Formula: see text]-NN), Naive Bayes, and probabilistic neural network were used to evaluate the highest performance measure using minimum number of features in classifying normal and dry AMD classes. The proposed framework obtained an average accuracy of 93.70%, sensitivity of 91.11%, and specificity of 96.30% using KLD ranking and SVM classifier. We have also formulated an AMD Risk Index using selected features to classify the normal and dry AMD classes using one number. The proposed system can be used to assist the clinicians and also for mass AMD screening programs. PMID- 25112274 TI - Evaluation of the hemodynamics in straight 6-mm and tapered 6- to 8-mm grafts as upper arm hemodialysis vascular access. AB - The present study is intended to investigate and compare the hemodynamics in two different sizes of hemodialysis arteriovenous grafts for upper arm hemodialysis vascular access: 8-mm tapered to 6-mm at the arterial side and straight 6 mm. A computational simulation approach is presented for this study, which is validated against the available experimental and numerical pressure measurements in the literature. The imposed boundary conditions at the arterial inlet and venous outlet boundaries of the models are physiological velocity and pressure waveforms, respectively. Blood flow fields and distribution patterns of the hemodynamic indices including wall shear stress (WSS) as one of the major hemodynamic parameters of the cardiovascular system and spatial wall shear stress gradient (SWSSG) as an indicator of disturbed flow patterns and hence susceptible sites of lesion developments are analyzed and compared between the two grafts. The tapered 6- to 8-mm graft seemingly is associated with less disturbed flow patterns within the venous anastomosis (VA) and the vein downstream while benefiting from higher blood flow rates within. Also, it shows a definitive advantage in terms of WSS and SWSSG distribution patterns around the VA and throughout the vein downstream with significantly lower values, which reduce the risk of thrombosis formation and stenotic lesion developments. The only disadvantage encountered in using 6- to 8-mm tapered graft is higher values of hemodynamic parameters at the arterial junction attributable to its significantly higher mean blood flow rate within. The results clearly indicate that the tapered 6- to 8-mm graft entirely outperforms straight 6-mm graft hemodynamically as an upper arm hemodialysis vascular access graft and confirms clinical data in the literature, which suggests advantageous use of tapered 6- to 8-mm grafts in the creation of upper arm brachioaxillary hemodialysis vascular access grafts in selected groups of patients with expectably higher patency rates and lower complications. PMID- 25112276 TI - Gene mutation may increase risk of breast cancer by up to nine times. PMID- 25112275 TI - Platelets promote mitochondrial uncoupling and resistance to apoptosis in leukemia cells: a novel paradigm for the bone marrow microenvironment. AB - Here we report that leukemia cell lines and primary CD34+ leukemic blasts exposed to platelet rich plasma (PRP) or platelet lysates (PL) display increased resistance to apoptosis induced by mitochondria-targeted agents ABT-737 and CDDO Me. Intriguingly, leukemia cells exposed to platelet components demonstrate a reduction in mitochondrial membrane potential (DeltaPsiM) and a transient increase in oxygen consumption, suggestive of mitochondrial uncoupling. Accompanying the ranolazine-sensitive increase in oxygen consumption, a reduction in triglyceride content was also observed in leukemia cells cultured with platelet components indicating that lipolysis and fatty acid oxidation may support the molecular reduction of oxygen in these cells. Mechanistically, platelet components antagonized Bax oligomerization in accordance with previous observations supporting an antiapoptotic role for fatty acid oxidation in leukemia cells. Lastly, substantiating the notion that mitochondrial uncoupling reduces oxidative stress, platelet components induced a marked decrease in basal and rotenone-induced superoxide levels in leukemia cells. Taken together, the decrease in DeltaPsiM, the transient increase in ranolazine-sensitive oxygen consumption, the reduction in triglyceride levels, and the reduced generation of superoxide, all accompanying the increased resistance to mitochondrial apoptosis, substantiate the hypothesis that platelets may contribute to the chemoprotective sanctuary of the bone marrow microenvironment via promotion of mitochondrial uncoupling. PMID- 25112277 TI - Male genital mutilation (amputation) and its complications: a case report. AB - BACKGROUND: Genital losses from ritual attacks are often reported in the media and often discussed in the social media but are hardly reported in medical literature. Male genital mutilation (MGM) refers to permanent modification of the external genitalia that involves ablation of genital tissues.When found, it is usually as a consequence of poor circumcision skills, auto mutilation/castration or genital injuries caused by attacks or accidents. Male circumcision on its own is widely regarded as a rather safe and acceptable practice which is known to have some health benefits and in keeping with several religious customs as rite of passage. Outside of professional performed circumcision, MGM is usually associated with dark arts and malicious intentions like witchcraft or as a consequence of torture of prisoners of war for information. CASE PRESENTATION: In this case we describe a 5-year old Ugandan boy who had his genitals mutilated in bizarre circumstances within a ritual attack. He survived and a urethrostomy was fashioned. CONCLUSION: There is need to document more of these cases in order to gather enough information to inform prevention and treatment strategies. Issues of hormonal replacement therapy (HRT) and possible sex change require much debate. These genital sex changing operations should preferably be avoided until a child can fully participate in decision making. PMID- 25112278 TI - Nonlesions, misdiagnoses, missed diagnoses, and other interpretive challenges in fish histopathology studies: a guide for investigators, authors, reviewers, and readers. AB - Differentiating salient histopathologic changes from normal anatomic features or tissue artifacts can be decidedly challenging, especially for the novice fish pathologist. As a consequence, findings of questionable accuracy may be reported inadvertently, and the potential negative impacts of publishing inaccurate histopathologic interpretations are not always fully appreciated. The objectives of this article are to illustrate a number of specific morphologic findings in commonly examined fish tissues (e.g., gills, liver, kidney, and gonads) that are frequently either misdiagnosed or underdiagnosed, and to address related issues involving the interpretation of histopathologic data. To enhance the utility of this article as a guide, photomicrographs of normal and abnormal specimens are presented. General recommendations for generating and publishing results from histopathology studies are additionally provided. It is hoped that the furnished information will be a useful resource for manuscript generation, by helping authors, reviewers, and readers to critically assess fish histopathologic data. PMID- 25112279 TI - Pharmacological inhibition of DGAT1 induces sebaceous gland atrophy in mouse and dog skin while overt alopecia is restricted to the mouse. AB - Diacylglycerol O-acyltransferase 1 (DGAT1) plays an important role in synthesizing lipids, and inhibitors of DGAT1 have been investigated as potential treatments for diabetes and metabolic diseases. DGAT1 knockout (-/-) mice are resistant to obesity, have increased sensitivity to insulin, and exhibit sebaceous gland atrophy and alopecia. Prolonged pharmacological inhibition of DGAT1 with AZD7687 in mice results in the same skin phenotype, including sebaceous gland atrophy and alopecia, as seen in the skin of DGAT1 (-/-) mice. AZD7687-mediated effects on the skin were dose- and time-dependent and reversible. They occurred only at substantial levels of continuous DGAT1 inhibition. Prolonged treatment of dogs with AZD7687 also resulted in sebaceous gland atrophy but did not result in the more adverse skin changes of hair loss and skin lesions. Our findings highlight a significant risk of generating the same lesions that were seen in mouse skin during clinical development of DGAT1 inhibitors in humans and also reveal a species difference in the effects on the skin, indicating that the mouse may be an especially sensitive species. Therefore, although human therapeutic doses may not have the same influence on skin morphology as seen in mice, monitoring of skin changes will be essential in clinical trials with DGAT1 inhibitors. PMID- 25112281 TI - The Relationship between Perceptual Decision Variables and Confidence in the Human Brain. AB - Perceptual confidence refers to the degree to which we believe in the accuracy of our percepts. Signal detection theory suggests that perceptual confidence is computed from an internal "decision variable," which reflects the amount of available information in favor of one or another perceptual interpretation of the sensory input. The neural processes underlying these computations have, however, remained elusive. Here, we used fMRI and multivariate decoding techniques to identify regions of the human brain that encode this decision variable and confidence during a visual motion discrimination task. We used observers' binary perceptual choices and confidence ratings to reconstruct the internal decision variable that governed the subjects' behavior. A number of areas in prefrontal and posterior parietal association cortex encoded this decision variable, and activity in the ventral striatum reflected the degree of perceptual confidence. Using a multivariate connectivity analysis, we demonstrate that patterns of brain activity in the right ventrolateral prefrontal cortex reflecting the decision variable were linked to brain signals in the ventral striatum reflecting confidence. Our results suggest that the representation of perceptual confidence in the ventral striatum is derived from a transformation of the continuous decision variable encoded in the cerebral cortex. PMID- 25112280 TI - The distribution of insertionally polymorphic endogenous retroviruses in breast cancer patients and cancer-free controls. AB - BACKGROUND: Integration of retroviral DNA into a germ cell can result in a provirus that is transmitted vertically to the host's offspring. In humans, such endogenous retroviruses (HERVs) comprise >8% of the genome. The HERV-K(HML-2) proviruses consist of ~90 elements related to mouse mammary tumor virus, which causes breast cancer in mice. A subset of HERV-K(HML-2) proviruses has some or all genes intact, and even encodes functional proteins, though a replication competent copy has yet to be observed. More than 10% of HML-2 proviruses are human-specific, having integrated subsequent to the Homo-Pan divergence, and, of these, 11 are currently known to be polymorphic in integration site with variable frequencies among individuals. Increased expression of the most recent HML-2 proviruses has been observed in tissues and cell lines from several types of cancer, including breast cancer, for which expression may provide a meaningful marker of the disease. RESULTS: In this study, we performed a case-control analysis to investigate the possible relationship between the genome-wide presence of individual polymorphic HML-2 proviruses with the occurrence of breast cancer. For this purpose, we screened 50 genomic DNA samples from individuals diagnosed with breast cancer or without history of the disease (n = 25 per group) utilizing a combination of locus-specific PCR screening, in silico analysis of HML-2 content within the reference human genome sequence, and high-resolution genomic hybridization in semi-dried agarose. By implementing this strategy, we were able to analyze the distribution of both annotated and previously undescribed polymorphic HML-2 proviruses within our sample set, and to assess their possible association with disease outcome. CONCLUSIONS: In a case-control analysis of 50 humans with regard to breast cancer diagnosis, we found no significant difference in the prevalence of proviruses between groups, suggesting common polymorphic HML-2 proviruses are not associated with breast cancer. Our findings indicate a higher level of putatively novel HML-2 sites within the population, providing support for additional recent insertion events, implying ongoing, yet rare, activities. These findings do not rule out either the possibility of involvement of such proviruses in a subset of breast cancers, or their possible utility as tissue-specific markers of disease. PMID- 25112282 TI - Control of Spontaneous Ca2+ Transients Is Critical for Neuronal Maturation in the Developing Neocortex. AB - Neural activity plays roles in the later stages of development of cortical excitatory neurons, including dendritic and axonal arborization, remodeling, and synaptogenesis. However, its role in earlier stages, such as migration and dendritogenesis, is less clear. Here we investigated roles of neural activity in the maturation of cortical neurons, using calcium imaging and expression of prokaryotic voltage-gated sodium channel, NaChBac. Calcium imaging experiments showed that postmigratory neurons in layer II/III exhibited more frequent spontaneous calcium transients than migrating neurons. To test whether such an increase of neural activity may promote neuronal maturation, we elevated the activity of migrating neurons by NaChBac expression. Elevation of neural activity impeded migration, and induced premature branching of the leading process before neurons arrived at layer II/III. Many NaChBac-expressing neurons in deep cortical layers were not attached to radial glial fibers, suggesting that these neurons had stopped migration. Morphological and immunohistochemical analyses suggested that branched leading processes of NaChBac-expressing neurons differentiated into dendrites. Our results suggest that developmental control of spontaneous calcium transients is critical for maturation of cortical excitatory neurons in vivo: keeping cellular excitability low is important for migration, and increasing spontaneous neural activity may stop migration and promote dendrite formation. PMID- 25112283 TI - Functional two-way analysis of variance and bootstrap methods for neural synchrony analysis. AB - BACKGROUND: Pairwise association between neurons is a key feature in understanding neural coding. Statistical neuroscience provides tools to estimate and assess these associations. In the mammalian brain, activating ascending pathways arise from neuronal nuclei located at the brainstem and at the basal forebrain that regulate the transition between sleep and awake neuronal firing modes in extensive regions of the cerebral cortex, including the primary visual cortex, where neurons are known to be selective for the orientation of a given stimulus. In this paper, the estimation of neural synchrony as a function of time is studied in data obtained from anesthetized cats. A functional data analysis of variance model is proposed. Bootstrap statistical tests are introduced in this context; they are useful tools for the study of differences in synchrony strength regarding 1) transition between different states (anesthesia and awake), and 2) affinity given by orientation selectivity. RESULTS: An analysis of variance model for functional data is proposed for neural synchrony curves, estimated with a cross-correlation based method. Dependence arising from the experimental setting needs to be accounted for. Bootstrap tests allow the identification of differences between experimental conditions (modes of activity) and between pairs of neurons formed by cells with different affinities given by their preferred orientations. In our test case, interactions between experimental conditions and preferred orientations are not statistically significant. CONCLUSIONS: The results reflect the effect of different experimental conditions, as well as the affinity regarding orientation selectivity in neural synchrony and, therefore, in neural coding. A cross-correlation based method is proposed that works well under low firing activity. Functional data statistical tools produce results that are useful in this context. Dependence is shown to be necessary to account for, and bootstrap tests are an appropriate method with which to do so. PMID- 25112284 TI - An unusual case of abdominal distension with constipation. PMID- 25112285 TI - Annual review of children with tuberous sclerosis. AB - Tuberous sclerosis complex is a complex childhood disorder characterised by the formation of hamartomas in multiple organs. Annual review of this disease is recommended to monitor the development of complications. We aim to provide a concise, evidence-based framework to assist clinicians during this annual review. We focus on the following areas: (A) what questions need to be asked during annual review, (B) which areas need emphasis on examination, (C) when is an investigation required and (D) referral to tertiary specialists and other members of the multidisciplinary team. It should also be noted that there are ongoing debates regarding screening intervals in certain areas. These include the frequency, modality of screening and degree of intervention for astrocytomas and renal angiomyolipomas. This review seeks to summarise the product of the ongoing debates, and provide evidence-based suggestions in light of the uncertainty. PMID- 25112287 TI - Alpha-lipoic acid enhances DMSO-induced cardiomyogenic differentiation of P19 cells. AB - Alpha-lipoic acid (alpha-LA) is a potent antioxidant that acts as an essential cofactor in mitochondrial dehydrogenase reactions. alpha-LA has been shown to possess anti-inflammatory and cytoprotective properties, and is used to improve symptoms of diabetic neuropathy. However, the role of alpha-LA in stem cell differentiation and the underlying molecular mechanisms remain unknown. In the present study, we showed that alpha-LA significantly promoted dimethyl sulfoxide (DMSO)-induced cardiomyogenic differentiation of mouse embryonic carcinoma P19 cells. alpha-LA dose dependently increased beating embryonic body (EB) percentages of DMSO-differentiated P19 cells. The expressions of cardiac specific genes TNNT2, Nkx2.5, GATA4, MEF2C, and MLC2V and cardiac isoform of troponin T (cTnT)-positively stained cell population were significantly up-regulated by the addition of alpha-LA. We also demonstrated that the differentiation time after EB formation was critical for alpha-LA to take effect. Interestingly, without DMSO treatment, alpha-LA did not stimulate the cardiomyogenic differentiation of P19 cells. Further investigation indicated that collagen synthesis-enhancing activity, instead of the antioxidative property, plays a significant role in the cardiomyogenic differentiation-promoting function of alpha-LA. These findings highlight the potential use of alpha-LA for regenerative therapies in heart diseases. PMID- 25112286 TI - Fifteen minute consultation: managing neonatal and childhood herpes encephalitis. AB - Herpes simplex encephalitis (HSE) is the most common single cause of viral encephalitis in infants and children. Treated or untreated, it can be associated with considerable morbidity and mortality, and its presentation is usually insidious and non-specific. Prompt and careful investigation is important in order to establish the diagnosis so that treatment can be optimised. We address some common questions arising when diagnosing and treating presumed HSE throughout childhood. PMID- 25112288 TI - The influence of nitroglycerin on the proliferation of endothelial progenitor cells from peripheral blood of patients with coronary artery disease. AB - Endothelial progenitor cells (EPCs) are associated with vascular repairing and progression of atherosclerotic lesion. It may lead to coronary artery disease (CAD) if circulating EPCs lose their function. Continuous nitroglycerin (NTG) therapy causes increased vascular oxidative stress and endothelial dysfunction. The aim of this study was to investigate the effects of NTG on the proliferation of human peripheral blood-derived EPCs. EPC cultures, collected from 60 CAD patients and cultured for 7-12 days, were treated with different concentrations of NTG (0.0, 0.3, 1.0, 2.0, 7.5, 15.0, and 20.0 mg/l) for 72 h, respectively. The cell counts and proliferative activities of EPC; the levels of vascular endothelial growth factor-A (VEGF-A), nitric oxide (NO) and peroxynitrite (ONOO( )) in culture medium; and the level of reactive oxygen species (ROS) in adherent cells were measured. Compared with control (0.0 mg/l NTG), the cell number and proliferative activities of EPCs were increased when treated with 1.0 mg/l NTG and reached maximum level when NTG concentration was 7.5 mg/l. However, there was a significant reduction when treated with higher doses of NTG (>=15.0 mg/l). Meanwhile, VEGF-A expression reached its maximal expression with 7.5 mg/l NTG, but gradually declined by incubation with higher doses of NTG. There was a linear relationship between NO level and NTG concentration, but no changes of ONOO(-) and ROS levels were found when EPCs were incubated with 0.3-7.5 mg/l NTG. However, ONOO(-) and ROS levels were significantly increased when incubated with 15 and 20 mg/l NTG. Our data demonstrated that moderate dose of NTG may stimulate the proliferative activities of EPCs isolated from CAD patients. PMID- 25112289 TI - Identification of biochemical association of phycobilisome with photosystems in cyanobacterial state transition. AB - State transition is a short-term balance mechanism of energy distribution between photosystem II (PSII) and PSI. Although light-induced state transition in cyanobacteria has been suggested to depend completely on the phycobilisome (PBS) movement between PSII and PSI, the biochemical evidence has not been clearly shown. In this study, we locked the association of PBS with PSII or PSI using glycinebetaine when cells attain State 1 or 2 by exposure to light of blue or green, respectively. Subsequently, the PBS-reaction centers were resolved by blue native polyacrylamide gel electrophoresis and two-dimensional electrophoresis, and then identified by western blot analysis. The results showed that in wild type (WT) Synechocystis sp. strain PCC 6803, the PBS core always co-migrates with the PSII dimer during light-induced State 1-State 2 transition, but its rod leaves the PSII dimer in State 2 regardless of its co-migration in State 1. In the light-induced State 2, the co-migration of PBS rod with PSI trimer was observed in WT, but not in DeltandhB (M55), a State-2-transition-deficient mutant. This study first provided the biochemical evidence for the association of PBS with photosystems during cyanobacterial state transition. PMID- 25112299 TI - Stem cells: epigenome reprogramming--of mice and men. PMID- 25112300 TI - Biotransformation and chemotaxis of 4-chloro-2-nitrophenol by Pseudomonas sp. JHN. AB - Pseudomonas sp. JHN decolourized and biotransformed 4-chloro-2-nitrophenol (4C2NP) in the presence of additional carbon source. The effect of the various concentrations of the 4C2NP was studied on the decolourization of 4C2NP by Pseudomonas sp. JHN. It was observed that strain JHN decolourized and biotransformed 4C2NP up to concentration of 0.6 mM. Gas chromatography and gas chromatography-mass spectrometry detected 5-chloro-2-methylbenzoxazole as a major metabolite of the co-metabolism of 4C2NP. Furthermore, strain JHN exhibits positive chemotaxis toward 4C2NP based on the drop plate and capillary assays. This is the first report of the chemotaxis toward 4C2NP by any bacterium. PMID- 25112301 TI - Analyzing periodic and random textured silicon thin film solar cells by Rigorous Coupled Wave Analysis. AB - A simple and fast method was developed to determine the quantum efficiency and short circuit current of thin-film silicon solar cells prepared on periodically or randomly textured surfaces. The optics was studied for microcrystalline thin film silicon solar cells with integrated periodic and random surface textures. Rigorous Coupled Wave Analysis (RCWA) was used to investigate the behaviour of the solar cells. The analysis of the periodic and random textured substrates allows for deriving optimal surface textures. Furthermore, light trapping in periodic and randomly textured substrates will be compared. PMID- 25112293 TI - Context-dependent control of alternative splicing by RNA-binding proteins. AB - Sequence-specific RNA-binding proteins (RBPs) bind to pre-mRNA to control alternative splicing, but it is not yet possible to read the 'splicing code' that dictates splicing regulation on the basis of genome sequence. Each alternative splicing event is controlled by multiple RBPs, the combined action of which creates a distribution of alternatively spliced products in a given cell type. As each cell type expresses a distinct array of RBPs, the interpretation of regulatory information on a given RNA target is exceedingly dependent on the cell type. RBPs also control each other's functions at many levels, including by mutual modulation of their binding activities on specific regulatory RNA elements. In this Review, we describe some of the emerging rules that govern the highly context-dependent and combinatorial nature of alternative splicing regulation. PMID- 25112303 TI - Impact of Educational Levels and Health Literacy on Community Acetaminophen Knowledge. AB - Patient understanding of acetaminophen is important for its safe and appropriate self-use. A cross-sectional survey was conducted in the San Francisco Bay Area to determine the impact of educational level, patient health literacy score, and other demographic characteristics on acetaminophen knowledge. A 17-item, in person, paper-and-pen questionnaire containing questions about demographics and acetaminophen knowledge was administered to 311 adults outside 5 local grocery stores in varying socioeconomic communities. Knowledge assessed was whether Tylenol-McNeil contains acetaminophen, maximum daily dose, and primary organ affected by toxicity. Participant health literacy was evaluated using the Rapid Estimate of Adult Literacy in Medicine-Short Form (REALM-SF) test. Of the 300 who successfully completed the study, only 3.8% of all subjects were able to answer all 3 acetaminophen knowledge questions correctly regardless of educational level or health literacy score. This reaffirms that a lack of appropriate acetaminophen knowledge remains present in the general population, and further efforts to educate patients will be needed to prevent adverse events. PMID- 25112302 TI - Efficacy of lidocaine in patients receiving palliative care with opioid refractory cancer pain with a neuropathic component: study protocol for a randomized controlled study. AB - BACKGROUND: The management of patients suffering from opioid-refractory cancer pain with a neuropathic component remains an important challenge for healthcare workers. Only one retrospective study specifically reported the use of intravenous (IV) lidocaine amongst the palliative care unit population, the study found that there was a positive response to this therapy. These preliminary uncontrolled results need to be confirmed by randomized controlled trials. The primary objective of this study is to assess the analgesic efficacy of IV lidocaine in patients in palliative care suffering from opioid-refractory cancer pain with a neuropathic component. The secondary objectives are to assess the tolerance of, symptomatology, and patient satisfaction with the therapeutic approach. METHODS/DESIGN: This will be a multicenter, prospective, randomized, placebo-controlled, double-blind, two-parallel group study. It will take place in eight adult palliative care units across France. The main inclusion criteria are as follows: adult patients suffering from opioid-refractory cancer pain with a neuropathic component, and those receiving palliative care as defined by French Society of Palliative and Support Care. Participants will be randomized (1:1 allocation ratio) to one of two treatment groups: a) lidocaine-experimental group (intravenous lidocaine), or b) placebo-control group (intravenous saline solution). Evaluation assessments will be taken at baseline (T0 randomization), 40 minutes (T1), 120 minutes (T2), 12 hours (T3), 24 hours (T4), 48 hours (T5), and 14 days (T6) after baseline. The primary endpoint is change in the pain level between T0 and T1. The secondary endpoints are: changes in the pain level between T0 and other times, intensity of the neuropathic pain component, daily opioid consumption, symptoms (as classified by the MD Anderson Symptom Inventory), adverse events, and patient's satisfaction (measured using the Pain Treatment Satisfaction Scale). A sample size of 200 individuals will be needed to obtain 90% power to detect a 25% difference in pain success at T1 between the two groups; pain success is classified as a 30% decrease in the pain level between T0 and T1 (10% of patients lost to follow-up expected). DISCUSSION: The randomized, double-blind, placebo-controlled design is the most appropriate design to demonstrate the efficacy of a new experimental intervention (Evidence-Based Medicine Working Group classification). National and international recommendations could be updated based on the findings of this study. TRIAL REGISTRATION: Current controlled trials NCT02137954 (registration date: 7 May 2014). PMID- 25112305 TI - Symptomatic Overlap and Therapeutic Opportunities in Primary Headache. AB - Headache, a nearly universal experience, remains costly, disabling, and often suboptimally managed. The most common presentations in the United States are migraine, tension-type headache (TTH) and "sinus" headache, but their extensive symptomatic overlap suggests that these conditions can be approached as variations in the same underlying pathology and managed accordingly. We use case studies of patients with varying prior diagnoses (none, migraine, TTH, and sinus headache), as well as a 4-question diagnostic screening tool, to illustrate how pharmacists can use this conceptual framework to simplify identification, management, and referral of patients with primary headache conditions of uncertain etiology. PMID- 25112304 TI - Evaluation of Treatment Courses When Vancomycin Is Given Every 8 Hours in Adult Patients. AB - BACKGROUND: Several nomograms include recommendations to give intravenous (IV) vancomycin at 8-hour dosing intervals (Q8H). However, there is a lack of detailed data regarding this dosing recommendation. METHODS: A retrospective chart review of 100 patients who received 107 treatment courses of vancomycin Q8H for at least 5 days was performed. Distribution of vancomycin trough levels and rate of nephrotoxicity were evaluated. RESULTS: Median patient age was 38 years (interquartile range [IQR] 27-50 years), median weight was 67 kg (IQR 55-79 kg), and median creatinine clearance was 124 mL/min (IQR 101-147 mL/min). Median duration of Q8H dosing was 9 days (IQR 7-12 days). Within the initial 96 hours, only 7% (7 of 104) of maximum trough concentrations were >20 mg/L (median dose 15 mg/kg [IQR 15-18 mg/kg]). After 96 hours of Q8H dosing, 34% (30 of 89) of maximum troughs were >20 mg/L (median dose 17 mg/kg [IQR 15-20 mg/kg]), P = .0005. The rate of nephrotoxicity was 4%. CONCLUSION: We observed an increase in the percentage of trough levels >20 mg/L later during treatment courses of vancomycin IV Q8H with a relatively small corresponding increase in vancomycin dose. Close monitoring of trough levels (eg, every 3 days) with prolonged courses of vancomycin IV Q8H is warranted. PMID- 25112306 TI - A Comprehensive Review of Potential Warfarin-Fruit Interactions. AB - PURPOSE: The aim of this review is to discuss possible interactions that may occur between warfarin and fruit products. METHODS: A literature search was conducted using the search terms: "warfarin (Coumadin(r)) and fruit interactions, warfarin and fruit, warfarin and fruit juice, case reports and clinical trials". RESULTS: A total of 23 citations (15 case reports and 7 controlled clinical trials) were reviewed. The majority of cases involved cranberry products, while pomegranate juice, avocado, grapefruit juice, mango, and papain were also implicated in reports of suspected warfarin-fruit interactions. Cranberry juice was also the most frequently studied fruit product. Other fruit products evaluated with warfarin in controlled clinical trials were cranberry concentrate and grapefruit juice. CONCLUSION: Although a number of case reports have been published that suggest warfarin has the potential to interact with several fruit products, it is difficult to determine their relevance, as scientific evidence is scarce. Until further information is available, clinicians may want to encourage patients to consume cranberry products and grapefruit juice in small to moderate quantities and to inquire about the recent consumption of mangos, pomegranate juice, and avocados when taking a dietary history or when assessing possible causes for international normalized ratio (INR) instability. PMID- 25112309 TI - Transthyretin-type cerebral amyloid angiopathy: a serious complication in post transplant patients with familial amyloid polyneuropathy. PMID- 25112307 TI - Brief intervention for medication-overuse headache in primary care. The BIMOH study: a double-blind pragmatic cluster randomised parallel controlled trial. AB - BACKGROUND: Medication-overuse headache (MOH) is common in the general population. We investigated effectiveness of brief intervention (BI) for achieving drug withdrawal in primary care patients with MOH. METHODS: The study was double-blind, pragmatic and cluster-randomised controlled. A total of 25,486 patients (age 18-50) from 50 general practitioners (GPs) were screened for MOH. GPs defined clusters and were randomised to receive BI training (23 GPs) or to continue business as usual (BAU; 27 GPs). The Severity of Dependence Scale was applied as a part of the BI. BI involved feedback about individual risk of MOH and how to reduce overuse. Primary outcome measures were reduction in medication and headache days/month 3 months after the intervention and were assessed by a blinded clinical investigator. RESULTS: 42% responded to the postal screening questionnaire, and 2.4% screened positive for MOH. A random selection of up to three patients with MOH from each GP were invited (104 patients), 75 patients were randomised and 60 patients included into the study. BI was significantly better than BAU for the primary outcomes (p<0.001). Headache and medication days were reduced by 7.3 and 7.9 (95% CI 3.2 to 11.3 and 3.2 to 12.5) days/month in the BI compared with the BAU group. Chronic headache resolved in 50% of the BI and 6% of the BAU group. CONCLUSIONS: The BI method provides GPs with a simple and effective instrument that reduces medication-overuse and headache frequency in patients with MOH. TRIAL REGISTRATION NUMBER: NCT01314768. PMID- 25112308 TI - A study of up to 12 years of follow-up of Friedreich ataxia utilising four measurement tools. AB - OBJECTIVE: To explore the progression of Friedreich ataxia by analysing the change in scores of four clinical measures (the Friedreich Ataxia Rating Scale (FARS), the International Cooperative Ataxia Rating Scale (ICARS), the Functional Independence Measure (FIM) and the Modified Barthel Index (MBI)) over a period of up to 12 years, to ascertain the effects of clinical variables on performance of these measures, and to determine the most sensitive rating scale for measuring disease progression. METHODS: We measured the disease progression of up to 147 individuals against disease duration grouped into 5-year intervals. Additional subgroups were created to study the effects of the size of the smaller FXN intron 1 GAA repeat size (GAA1) and onset age on rating scale performance. RESULTS: Both the FARS and ICARS demonstrated greater change in the first 20 years post disease onset than in the subsequent 20 years during which there was little change in the mean score. While the FIM and MBI continued to deteriorate beyond 20 years post disease onset, floor effects were noted. As measured by the FARS, individuals with a larger GAA1 repeat were found to progress more quickly in the first 20 years of disease. CONCLUSIONS: Individuals with larger GAA1 repeat sizes and earlier ages of disease onset were shown to deteriorate at a faster rate and were associated with greater FARS and ICARS scores and lower FIM and MBI scores, which are indicative of greater disease severity. PMID- 25112310 TI - Contraceptive counselling and self-prescription of contraceptives of German gynaecologists: results of a nationwide survey. AB - OBJECTIVE: To evaluate the attitude toward contraceptive methods of gynaecologists who, in Germany, are the sole prescribers of contraceptives. METHODS: An anonymous questionnaire was sent to 9545 gynaecologists inquiring about factors involved in their prescription of contraceptives, the contraceptives they preferred, and those they would recommend to their daughter, if they had one. RESULTS: The response rate of this survey was 21% (N = 2016). The combined oral contraceptive (COC) was the most commonly prescribed method followed by the levonorgestrel-releasing intrauterine system (LNG-IUS), the vaginal ring, the progestin-only pill (POP), the patch, and the progestin-only injectables. Of the respondents 51% would never prescribe the patch and 45% would never prescribe the hormonal implant at all; 61% would choose the LNG-IUS for themselves/for their partner; 18% would opt for a COC and 8% for the vaginal ring. Concerning their imaginary daughter, 71% would prefer a COC, 26% the ring, and 9% the LNG-IUS. The first counselling session lasted 13.8 +/- 4.9 min, and the provision of information on the occasion of following visits 6.6 +/- 3.2 min. CONCLUSION: The contraceptives most prescribed by German gynaecologists were COCs, followed by the LNG-IUS, the vaginal ring, and POPs. The spectrum of contraceptives preferred for personal use differed in some ways from those prescribed to patients. Reasons for this discrepancy should be investigated. PMID- 25112311 TI - Osteogenic differentiation of amniotic epithelial cells: synergism of pulsed electromagnetic field and biochemical stimuli. AB - BACKGROUND: Pulsed electromagnetic field (PEMF) is a non-invasive physical therapy used in the treatment of fracture nonunion or delayed healing. PEMF can facilitate the osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Amniotic epithelial cells (AECs) have been proposed as a potential source of stem cells for cell therapy. However, whether PEMF could modulate the osteogenic differentiation of AECs is unknown. In the present study, the effects of PEMF on the osteogenic differentiation of AECs were investigated. METHODS: AECs were isolated from amniotic membrane of human placenta by trypsin digestion and were induced by PEMF and/or osteo-induction medium. After 21 days we used real time RT-PCR and immunocytochemistry to study the expression of osteoblast markers. The signal transduction of osteogenesis was further investigated. RESULTS: The PEMF stimulation, or osteo-induction medium alone could induce osteogenic differentiation of AECs, as shown by expression of osteoblast specific genes and proteins including alkaline phosphatase and osteocalcin. Furthermore, a combination of PEMF and osteo-induction medium had synergy effects on osteogenic differentiation. In our study, the gene expression of BMP-2, Runx2, beta-catenin, Nrf2, Keap1 and integrinbeta1 were up-regulated in the osteogenic differentiation of AECs induced by PEMF and/or osteo-induction medium. CONCLUSIONS: Combined application of PEMF and osteo-induction medium is synergistic for the osteogenic differentiation of AECs. It might be a novel approach in the bone regenerative medicine. PMID- 25112312 TI - Protective immunity of 56-kDa type-specific antigen of Orientia tsutsugamushi causing scrub typhus. AB - Scrub typhus, caused by infection with Orientia tsutsugamushi, is a mite-borne zoonotic disease endemic to the Asian-Pacific region. In Korea, the incidence of this disease has increased with climate changes, and over 10,000 cases of infection were reported in 2013. Although this infection is treatable with antibiotics such as doxycycline and azithromycin, an effective prophylactic vaccine against O. tsutsugamushi would be more desirable for preventing scrub typhus in endemic areas. In this study, we investigated the 56-kDa type-specific antigen (TSA56), which is a major outer membrane protein of O. tsutsugamushi, as a vaccine candidate. Intranasal immunization of recombinant TSA56 (rec56) induced a higher level of TSA56- specific IgG than that induced by intramuscular immunization of tsa56-expressing DNA (p56). Both types of immunization induced a cell-mediated immune response to TSA56, as demonstrated by the splenic cell proliferation assay. Mice immunized with p56, followed by rec56 plus heat-labile enterotoxin B subunit from E. coli, had a stronger protection from a homologous challenge with the O. tsutsugamushi Boryong strain than with other combinations. Our preliminary results suggest that an effective human vaccine for scrub typhus can include either recombinant TSA56 protein or tsa56-expressing DNA, and provide the basis for further studies to optimize vaccine performance using additional antigens or different adjuvants. PMID- 25112314 TI - Cloning and characterization of a multidomain GH10 xylanase from Paenibacillus sp. DG-22. AB - The xynC gene, which encodes high molecular weight xylanase from Paenibacillus sp. DG-22, was cloned and expressed in Escherichia coli, and its nucleotide sequence was determined. The xynC gene comprised a 4,419 bp open reading frame encoding 1,472 amino acid residues, including a 27 amino acid signal sequence. Sequence analysis indicated that XynC is a multidomain enzyme composed of two family 4_9 carbohydrate-binding modules (CBMs), a catalytic domain of family 10 glycosyl hydrolases, a family 9 CBM, and three S-layer homologous domains. Recombinant XynC was purified to homogeneity by heat treatment, followed by Avicel affinity chromatography. SDS-PAGE and zymogram analysis of the purified enzyme identified three active truncated xylanase species. Protein sequencing of these truncated proteins showed that all had identical N-terminal sequences. In the protein characterization, recombinant XynC exhibited optimal activity at pH 6.5 and 65 degrees C and remained stable at neutral to alkaline pH (pH 6.0 10.0). The xylanase activity of recombinant XynC was strongly inhibited by 1 mM Cu(2+) and Hg(2+), whereas it was noticeably enhanced by 10 mM dithiothreitol. The enzyme exhibited strong activity towards xylans, including beechwood xylan and arabinoxylan, whereas it showed no cellulase activity. The hydrolyzed product patterns of birchwood xylan and xylooligosaccharides by thin-layer chromatography confirmed XynC as an endoxylanase. PMID- 25112313 TI - Quorum quenching bacteria isolated from the sludge of a wastewater treatment plant and their application for controlling biofilm formation. AB - Bacteria recognize changes in their population density by sensing the concentration of signal molecules, N-acyl-homoserine lactones (AHLs). AHL mediated quorum sensing (QS) plays a key role in biofilm formation, so the interference of QS, referred to as quorum quenching (QQ), has received a great deal of attention. A QQ strategy can be applied to membrane bioreactors (MBRs) for advanced wastewater treatment to control biofouling. To isolate QQ bacteria that can inhibit biofilm formation, we isolated diverse AHL-degrading bacteria from a laboratory-scale MBR and sludge from real wastewater treatment plants. A total of 225 AHLdegrading bacteria were isolated from the sludge sample by enrichment culture. To identify the enzyme responsible for AHL degradation in QQ bacteria, AHL-degrading activities were analyzed using cell-free lysate, culture supernatant, and whole cells. Afipia sp. and Acinetobacter sp. strains produced the intracellular QQ enzyme, whereas Pseudomonas sp. and Micrococcus sp. produced the extracellular QQ enzyme that was most likely to produce AHLacylase. AHL degrading activity was observed in whole-cell assay with the Microbacterium sp. and Rhodococcus sp. strains. There has been no report for AHL-degrading capability in the case of Streptococcus sp. and Afipia sp. strains. Finally, inhibition of biofilm formation by isolated QQ bacteria or enzymes was observed on glass slides and 96-well microtiter plates using crystal violet staining. QQ strains or enzymes not only inhibited initial biofilm development but also reduced established biofilms. PMID- 25112315 TI - Reverse micellar extraction of fungal glucoamylase produced in solid-state fermentation culture. AB - Partial purification of glucoamylase from solid-state fermentation culture was, firstly, investigated by reverse micellar extraction (RME). To avoid back extraction problems, the glucoamylase was kept in the original aqueous phase, while the other undesired proteins/ enzymes were moved to the reverse micellar organic phase. The individual and interaction effects of main factors (i.e., pH and NaCl concentration in the aqueous phase, and concentration of sodium bis-2 ethyl-hexyl-sulfosuccinate (AOT) in the organic phase) were studied using response surface methodology. The optimum conditions for the maximum recovery of the enzyme were pH 2.75, 100 mM NaCl, and 200 mM AOT. Furthermore, the optimum organic to aqueous volume ratio (Vorg/Vaq) and appropriate number of sequential extraction stages were 2 and 3, respectively. Finally, 60% of the undesired enzymes including proteases and xylanases were removed from the aqueous phase, while 140% of glucoamylase activity was recovered in the aqueous phase and the purification factor of glucoamylase was found to be 3.0-fold. PMID- 25112316 TI - Crystal structure of (S)-3-hydroxybutyryl-CoA dehydrogenase from Clostridium butyricum and its mutations that enhance reaction kinetics. AB - 3-Hydroxybutyryl-CoA dehydrogenase is an enzyme that catalyzes the second step in the biosynthesis of n-butanol from acetyl-CoA, in which acetoacetyl-CoA is reduced to 3-hydroxybutyryl-CoA. To understand the molecular mechanisms of n butanol biosynthesis, we determined the crystal structure of 3-hydroxybutyryl-CoA dehydrogenase from Clostridium butyricum (CbHBD). The monomer structure of CbHBD exhibits a two-domain topology, with N- and C-terminal domains, and the dimerization of the enzyme was mostly constituted at the C-terminal domain. The mode of cofactor binding to CbHBD was elucidated by determining the crystal structure of the enzyme in complex with NAD(+). We also determined the enzyme's structure in complex with its acetoacetyl-CoA substrate, revealing that the adenosine diphosphate moiety was not highly stabilized compared with the remainder of the acetoacetyl-CoA molecule. Using this structural information, we performed a series of sitedirected mutagenesis experiments on the enzyme, such as changing residues located near the substrate-binding site, and finally developed a highly efficient CbHBD K50A/K54A/L232Y triple mutant enzyme that exhibited approximately 5-fold higher enzyme activity than did the wild type. The increased enzyme activity of the mutant was confirmed by enzyme kinetic measurements. The highly efficient mutant enzyme should be useful for increasing the production rate of n-butanol. PMID- 25112317 TI - Improvement of Wuyiencin biosynthesis in Streptomyces wuyiensis CK-15 by identification of a key regulator, WysR. AB - Wuyiencin is produced by Streptomyces ahygroscopicus var. wuyiensis CK-15 and is widely used as an antifungal agent in agriculture. Analysis of wuyiencin biosynthetic gene clusters reveals wysR, a member of the LAL-family of transcriptional regulatory genes. WysR consists of an Nterminal PAS domain and a LuxR family C-terminal helix-turn-helix motif. However, the roles of wysR in wuyiencin biosynthesis are largely unknown. In this study, we showed that inactivation of wysR resulted in the complete loss of wuyiencin production, which could be restored by complementation with a single copy of wysR. Furthermore, we successfully increased wuyiencin production to a significantly higher level by overexpression of wysR in S. wuyiensis CK-15. Quantitative real-time RT-PCR analysis showed that WysR regulates wuyiencin biosynthesis by modulating other putative regulatory genes. Thus, WysR was identified as an activator of wuyiencin biosynthesis, and overexpression of wysR gene proved to be an effective strategy for improving wuyiencin production. PMID- 25112318 TI - Oral administration of Lactobacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging. AB - Ultraviolet (UV) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage, including photoaging. In recent years, probiotics have gained interest due to their beneficial effects on skin health, such as inhibiting atopic dermatitis and improving skin immunity or inflammation. However, little is known about the effects of probiotics on UVBinduced photoaging. In this study, we evaluated the effect of Lactobacillus plantarum HY7714 against UVB-induced photoaging in human dermal fibroblasts and hairless mice. The results showed that L. plantarum HY7714 treatment effectively rescued UVB-reduced procollagen expression through the inhibition of UVB-induced matrix metalloproteinase (MMP)-1 expression in human dermal fibroblasts. Data from a western blot showed that L. plantarum HY7714 inhibited the phosphorylation of Jun N-terminal kinase, thereby suppressing the UVB-induced phosphorylation and expression of c-Jun. Oral administration of L. plantarum HY7714 clearly inhibited the number, depth, and area of wrinkles in hairless mouse skin. Histological data showed that L. plantarum HY7714 significantly inhibited UVB-induced epidermal thickness in mice. Western blot and zymography data also revealed that L. plantarum HY7714 effectively inhibited MMP-13 expression as well as MMP-2 and -9 activities in dermal tissue. Collectively, these results provide further insight regarding the skin biological actions of L. plantarum HY7714, a potential skin anti-photoaging agent. PMID- 25112319 TI - Insect cell surface expression of hemagglutinin (HA) of Egyptian H5N1 avian influenza virus under transcriptional control of whispovirus immediate early-1 promoter. AB - In the present study, whispovirus immediate early 1 promoter (ie-1) was used to initiate surface expression of the hemagglutinin (HA) protein of Egyptian H5N1 avian influenza virus (AIV) by using the baculovirus expression vector system. The HA gene and whispovirus ie-1 promoter sequence were synthesized as a fused expression cassette (ie1-HA) and successfully cloned into the pFastBac-1 transfer vector. The recombinant vector was transformed into DH10Bac competent cells, and the recombinant bacmid was generated via site-specific transposition. The recombinant bacmid was used for transfection of Spodoptera frugiperda (Sf-9) insect cells to construct the recombinant baculovirus and to induce expression of the HA protein of H5N1 AIV. The recombinant glycoprotein expressed in Sf-9 cells showed hemadsorption activity. Hemagglutination activity was also detected in both extra- and intracellular recombinant HAs. Both the HA and hemadsorption activities were inhibited by reference polyclonal anti-H5 sera. Significant expression of the recombinant protein was observed on the surface of infected insect cells by using immunofluorescence. SDS-PAGE analysis of the expressed protein revealed the presence of a visually distinguishable band of ~63 kDa in size, which was absent in the non-infected cell control. Western blot analysis confirmed that the distinct 63 kDa band corresponded to the recombinant HA glycoprotein of H5N1 AIV. This study reports the successful expression of the HA protein of H5N1 AIV. The expressed protein was displayed on the plasma membrane of infected insect cells under the control of whispovirus ie-1 promoter by using the baculovirus expression vector system. PMID- 25112320 TI - Higher biomass productivity of microalgae in an attached growth system, using wastewater. AB - Although most algae cultivation systems are operated in suspended culture, an attached growth system can offer several advantages over suspended systems. Algal cultivation becomes light-limited as the microalgal concentration increases in the suspended system; on the other hand, sunlight penetrates deeper and stronger in attached systems owing to the more transparent water. Such higher availability of sunlight makes it possible to operate a raceway pond deeper than usual, resulting in a higher areal productivity. The attached system achieved 2.8-times higher biomass productivity and total lipid productivity of 9.1 g m(-2) day(-1) and 1.9 g m(-2) day(-1), respectively, than the suspended system. Biomass productivity can be further increased by optimization of the culture conditions. Moreover, algal biomass harvesting and dewatering were made simpler and cheaper in attached systems, because mesh-type substrates with attached microalgae were easily removed from the culture and the remaining treated wastewater could be discharged directly. When the algal biomass was dewatered using natural sunlight, the palmitic acid (C16:0) content increased by 16% compared with the freeze drying method. There was no great difference in other fatty acid composition. Therefore, the attached system for algal cultivation is a promising cultivation system for mass biodiesel production. PMID- 25112321 TI - Different immune regulatory potential of Lactobacillus plantarum and Lactobacillus sakei isolated from Kimchi. AB - It is known that lactic acid bacteria (LAB) have many beneficial health effects, including antioxidative activity and immune regulation. In this study, the immune regulatory effects of Lactobacillus sakei and Lactobacillus plantarum, which are found in different types of kimchi, were evaluated. L. sakei and its lipoteichoic acid (LTA) have greater immune stimulating potential in IL-12, IFN-gamma, and TNF alpha production as compared with L. plantarum in an in vitro condition. On the other hand, L. plantarum is assumed to repress the Th1 immune response in murine experiments. After being injected with LPS, L. plantarum-fed mice maintained a healthier state, and the level of TNF-alpha in their blood was lower than in other bacterial strainfed mice and in the LPS-only control mice. Additionally, IL 12 production was significantly decreased and the production of IL-4 was greatly increased in the splenocytes from L. plantarum-fed mice. Further experiments revealed that the pre-injection of purified LTA from L. plantarum (pLTA), L. sakei (sLTA), and S. aureus (aLTA) decreased TNF-alpha and IL-4 production in LPS injected mice. Mouse IL-12, however, was significantly increased by aLTA pre injection. In conclusion, the L. sakei and L. plantarum strains have immune regulation effects, but the effects differ in cytokine production and the regulatory effects of the Th1/Th2 immune response. PMID- 25112323 TI - Systematic revision of the family Hoplitomerycidae Leinders, 1984 (Artiodactyla: Cervoidea), with the description of a new genus and four new species. AB - Six species of the cervoid genus Hoplitomeryx are currently recognized from the Late Miocene sites of Gargano and Scontrone, in Italy: H. matthei Leinders, 1984, H. apruthiensis Mazza & Rustioni, 2011, H. apulicus Mazza & Rustioni, 2011, H. falcidens Mazza & Rustioni, 2011, H. magnus Mazza & Rustioni, 2011, and H. minutus Mazza & Rustioni, 2011. These species are interpreted as members of an anagenetic series in these two localities, which are considered as part of the same bioprovince but with different geological ages. Comparative analysis of postcranial, dental, and cranial material from Hoplitomerycidae resulted in the reinterpretation of this current taxonomic arrangement. Two distinct genera can be distinguished. The new genus Scontromeryx is restricted to Scontrone (Early Tortonian) and is characterised by the presence of second upper and lower premolars and the absence of a nasal (median) horn. Hoplitomeryx is restricted to Gargano (Middle and/or Late Tortonian), and is characterized by the loss of the second premolar and presence of a nasal horn. Both genera are characterized by orbital appendages in some species, but the morphology of these appendages differs between the genera. Six species can be recognized for Scontromeryx gen. n.: S. minutus (type species), S. falcidens, S. apulicus, S. apruthiensis, S. magnus (new combinations) and the newly described S. mazzai sp. n.. Hoplitomeryx is represented by the H. matthei (type species) and 3 newly described species H. devosi sp. n., H. macpheei sp. n. and H. kriegsmani sp. n.. These two multispecies assemblages are best explained as independent adaptive radiations with the two genera as sister taxa. There is no evidence that the two localities were connected during the Late Miocene. PMID- 25112322 TI - Molecular and biochemical characteristics of beta-propeller phytase from marine Pseudomonas sp. BS10-3 and its potential application for animal feed additives. AB - Phytate is an antinutritional factor that impacts the bioavailability of essential minerals such as Ca(2+), Mg(2+), Mn(2+), Zn(2+), and Fe(2+) by forming insoluble mineral-phytate salts. These insoluble mineral-phytate salts are hydrolyzed rarely by monogastric animals, because they lack the hydrolyzing phytases and thus excrete the majority of them. The beta-propeller phytases (BPPs) hydrolyze these insoluble mineral-phytate salts efficiently. In this study, we cloned a novel BPP gene from a marine Pseudomonas sp. This Pseudomonas BPP gene (PsBPP) had low sequence identity with other known phytases and contained an extra internal repeat domain (residues 24-279) and a typical BPP domain (residues 280-634) at the C-terminus. Structurebased sequence alignment suggested that the N-terminal repeat domain did not possess the active-site residues, whereas the C-terminal BPP domain contained multiple calcium-binding sites, which provide a favorable electrostatic environment for substrate binding and catalytic activity. Thus, we overexpressed the BPP domain from Pseudomonas sp. to potentially hydrolyze insoluble mineral-phytate salts. Purified recombinant PsBPP required Ca(2+) or Fe(2+) for phytase activity, indicating that PsBPP hydrolyzes insoluble Fe(2+)-phytate or Ca2+-phytate salts. The optimal temperature and pH for the hydrolysis of Ca(2+)-phytate by PsBPP were 50 degrees C and 6.0, respectively. Biochemical and kinetic studies clearly showed that PsBPP efficiently hydrolyzed Ca(2+)-phytate salts and yielded myo-inositol 2,4,6 trisphosphate and three phosphate groups as final products. Finally, we showed that PsBPP was highly effective for hydrolyzing rice bran with high phytate content. Taken together, our results suggest that PsBPP has great potential in the animal feed industry for reducing phytates. PMID- 25112324 TI - Review and phylogeny of the geniculata group, genus Chinavia (Heteroptera: Pentatomidae), with notes on biogeography and morphological evolution. AB - Chinavia is one of the most diverse genera of Pentatomidae, comprising 80 species distributed in the Afrotropical, Neartic and Neotropical regions. Some groups of species have been proposed in the literature based on morphological similarities or phylogenetic analyses. The geniculata group was proposed to include C. geniculata, C. gravis and C. nigritarsis. However, eleven other species of Chinavia share somatic and genital characteristics with C. geniculata, C. gravis and C. nigritarsis, which allows hypothesizing the monophyly among these 14 species. In spite of the recent contributions to aspects of biology, immature stages and species catalogs in Chinavia, the definition of monophyletic groups within the genus and the establishment of boundaries among its species are essential to understand its diversity and to test hypotheses on biogeography and evolutionary biology. In this study we review the taxonomy of the geniculata group, test its monophyly and propose a phylogenetic hypothesis for the group. We discuss the phylogenetic relationships from a geographical perspective, and provide insights about morphological evolution. PMID- 25112325 TI - Review of the species of the genus Serrapinnus Malabarba, 1998 (Teleostei: Characidae: Cheirodontinae) from the rio Tocantins-Araguaia basin, with description of three new species. AB - Species of the genus Serrapinnus from the rio Tocantins-Araguaia basin are revised and three new species are described. Serrapinnus aster new species is diagnosed by the presence of scimitar-shaped ventral procurrent caudal-fin rays of mature males forming a semicircle and by the presence of 7-9 cusps on the premaxillary teeth; S. lucindai new species is distinguished from its congeners by the presence of a higher number of ventral procurrent caudal-fin rays (17 to 19); and S. tocantinensis new species differs from the remaining species of the genus by the elongation of the unbranched dorsal and pelvic-fin rays into filaments in mature males. Serrapinnus sterbai is recognized as broadly distributed in the Tocantins-Araguaia basin and is redescribed based on specimens from across its entire distribution. A key for the cheirodontines occurring in the Atlantic drainages of northeastern Brazil, from the rio Tocantins-Araguaia to the rio Paraguacu is provided. PMID- 25112326 TI - Vietnamese Issidae (Hemiptera, Fulgoroidea): new taxa, new records and new distribution data. AB - An updated list of Issidae known from Vietnam is provided. Two new species, one from the genus Darwallia Gnezdilov, 2010, and another one from a new genus are described from the Hon Ba massif in Central Vietnam. A key to species of the genus Darwallia is provided. Gelastyrella hainanensis Ran et Liang, 2006 is placed in synonymy under Thabena litaoensis Yang, 1994. This last taxon and the genus Gergithoides Schumacher, 1915 are recorded for the first time for Vietnamese fauna. New records in Vietnam are given for Tetrica philo Fennah, 1978 and Gergithus iguchii Matsumura, 1916. PMID- 25112327 TI - Afrotropical flower flies (Diptera: Syrphidae). A new genus and species from Kenya, with a review of the melanostomine group of genera. AB - A new genus and species of flower flies (Diptera: Syrphidae: Syrphinae: Syrphini) are described from central Africa (Kenya & Uganda), Afrostoma quadripunctatum. A key to the Afrotropical genera of the subfamily Syrphinae is given. A review of the melanostomine [Bacchini] genera and subgenera is provided along with a key to them. Phylogenetic placement of Afrostoma is included based on mitochondrial cytochrome c oxidase subunit I (COI) data. PMID- 25112328 TI - Leeonychiurus, a new genus from East Asia (Collembola: Onychiuridae: Onychiurini). AB - A new genus of Onychiurini including five species is described from East Asia. Leeonychiurus gen. nov. differs in its antennal III sensory organ with granulated sensory clubs and 11 chaetae in the distal whorl of tibiotarsi. The main diagnostic characters of the genera from the tribe Onychiurini and the five species from the new genus are summarized. A new species, Leeonychiurus fusongensis sp. nov., is reported from northeast China and it can be easily distinguished from other species of the genus by the number of dorsal and ventral pseudocelli. The known Korean species L. polychaetosus is redescribed by the examination of the type materials. PMID- 25112329 TI - A new species of Endecous Saussure, 1878 (Orthoptera, Gryllidae) from northeast Brazil with the first X1X20 chromosomal sex system in Gryllidae. AB - In this paper we describe a new species of Luzarinae cricket collected from the cave "Gruta de Ubajara, municipality of Ubajara, State of Ceara, Brazil, highlighting phallic sclerites morphology and chromosome complement as diagnostic characters. We presented meiotic and mitotic characterization in order to define the karyotype with 2n = 12 + X1X2?/12 + X1X1X2X2?. This represents the first record of X1X20 chromosomal sex system in Gryllidae. PMID- 25112330 TI - A new species of the genus Aspidiotes Schoenherr, 1847 (Coleoptera: Curculionidae: Tanymecini) from Middle Anatolia (Turkey). AB - A new species of Aspidiotes Schoenherr, 1847 (Curculionidae: Tanymecini) from Turkey is described and illustrated. Aspidiotes (Phaenognathus) candani sp. nov. is closely related to A. anatolicus (Colonnelli) but can be separated by eye shape, form of pronotum, form of setae on disc of elytra, surface morphology of scales, structure of aedeagus (in dorsal view) and form of spermatheca. PMID- 25112331 TI - Paracriodion Fragoso (Coleoptera: Cerambycidae: Cerambycinae): redefinition, with description of a new species from Bolivia. AB - The genus Paracriodion Fragoso, 1982, is redefined. A new species from Bolivia, P. morrisi sp. nov., is described. A key for Paracriodion species is included and new distributional data for P. romani (Aurivillius, 1926) are given. PMID- 25112332 TI - The genus Anahita from Wuyi Mountains, Fujian, China, with description of one new species (Araneae: Ctenidae). PMID- 25112333 TI - An updated checklist of Nepticulidae (Lepidoptera) of the Crimea, Sub Mediterranean SE Europe. AB - This updated checklist is intended to be a collaborative effort by a team of taxonomists to present a hitherto little known diversity of the Nepticulidae of the Crimea. A total of 64 species of Nepticulidae are listed. The following 26 species are recorded for the first time from the Crimea: Stigmella confusella (Wood & Walsingham, 1894), S. tiliae (Frey, 1856), S. microtheriella (Stainton, 1854), S. alnetella (Stainton, 1854), S. glutinosae (Stainton, 1858), S. desperatella (Frey, 1856), S. torminalis (Wood, 1890), S. crataegella (Klimesch, 1936), S. hahniella (Worz, 1937), S. catharticella (Stainton, 1853), S. malella (Stainton, 1854), S. rhamnella (Herrich-Schaffter, 1860), S. ulmivora (Fologne, 1860), S. trimaculella (Haworth, 1828), S. obliquella (Heinemann, 1862), S. tityrella (Stainton, 1854), S. carpinella (Heinemann, 1862), S. lemniscella (Zeller, 1839), S. plagicolella (Stainton, 1854), S. samiatella (Zeller, 1939), Bohemannia pulverosella (Stainton, 1849), Ectoedemia mahalebella (Klimesch, 1936), Fomoria septembrella (Stainton, 1849), Trifurcula silviae van Nieukerken, 1990, T. macedonica Z. Lastuvka & A. Lastuvka, 1998, T. eurema (Tutt, 1899). One species, Ectoedemia spinosella (Joannis, 1908), is excluded here from the list of the Nepticulidae of the Crimea. Thirty-nine selected species are illustrated with photographs of the leaf-mines, and forty-five species with photographs of genitalia. PMID- 25112334 TI - Review of the Stenothemus harmandi species-group (Coleoptera, Cantharidae), with description of six new species from China. AB - The diagnosis of the Stenothemus harmandi species-group is summarized, and all species are reviewed and keyed. S. harmandi (Bourgeois, 1902) is redescribed and six new species are described, S. fugongensis sp. nov. (CHINA: Yunnan), S. distortirudis sp. nov. (CHINA: Xizang), S. parallelus sp. nov. (CHINA: Xizang), S. septimus sp. nov. (CHINA: Xizang), S. leishanensis sp. nov. (CHINA: Guizhou) and S. laticollis sp. nov. (CHINA: Xizang). Each species treatment is provided with photos of habitus of male and abdominal sternite VIII of female, and illustrations of aedeagus. Additionally, S. subnitidus Svihla, 2005, S. holosericus Svihla, 2005 and S. orbiculatus Svihla, 2005 are provided with supplementary descriptions and photos of abdominal sternites VIII of females. Distribution maps are provided for each species of the S. harmandi species-group. PMID- 25112335 TI - Revision of the brachiopod genus Amphithyris (Rhynchonelliformea: Platidiidae) with descriptions of two new species. AB - The recent brachiopod genus Amphithyris Thomson belongs to the family Platidiidae and to date comprises five species, A. seminula (Philippi, 1836), A. buckmani Thomson, 1918, A. hallettensis Foster, 1974, A. richardsonae Campbell & Fleming, 1981 and A. parva MacKinnon, Hiller, Long & Marshall, 2008. Like other platidiid genera, Amphithyris has a worldwide distribution, but is mainly found in the southern hemisphere, with the exception of A. seminula which occurs in the Mediterranean Sea. This study is the first revision of the genus Amphithyris. We describe two new species, A. cavernicola n. sp. from the Queensland Plateau, Coral Sea, Australia and A. comitodentis n. sp. from deep waters east of the South Island, New Zealand. A. cavernicola n. sp. represents the first record of the genus from Australian waters, whereas A. comitodentis n. sp. is the first species in the genus recorded from the deep sea. Additionally, we identified the type material of A. seminula in the brachiopod collection of the Museum fur Naturkunde, Berlin and designated a lectotype for this species. Despite their simple shell morphology and few diagnostic features, we were able to clearly discriminate the (now) seven species by morphological (shell) characters such as absence/presence of a median septum, absence/presence of capillae, shell convexity and/or combinations of these. On the basis of all known records, the present distribution of Amphithyris spp. and a Cretaceous origin of the genus is discussed. PMID- 25112336 TI - The world's biogeographical regions revisited: global patterns of endemism in Tipulidae (Diptera). AB - This paper explores the distributional data of 4,224 Tipulidae (Insecta: Diptera) species to search for endemism patterns in a worldwide scale and to test the extent to which the global patterns of endemism of the group fit into previously proposed regionalization schemes, particularly Wallace's system and recent revisions of it. Large scale areas of endemism are assessed using the grid-based method implemented in VNDM. VNDM depends on the prior definition of the grid size for analysis, but a criterion for choosing beforehand a particular grid size is not clear. The same holds for the choice of the level of similarity in species composition selected for the calculation of consensus areas. In our study, we developed a methodological approach that helped defining objective criteria for choosing suitable values for these critical variables. Large-scale areas of endemism around the globe are identified and ranked according to endemicity levels: 1--West Palaearctic, 2--Nearctic, 3--East Palaearctic-Oriental, 4--West North America, 5--Australia, 6--Neotropical, 7--Sub-Saharan Africa, 8- Palaearctic, and 9--Middle East. Our main conclusion is that there are still some limitations in applying biogeographical classifications proposed mostly on the basis of vertebrate distribution to other taxonomic groups, such as the Tipulidae. While there is a general congruence of the broad-scale areas of endemism of tipulids with previously proposed regionalization schemes, for some areas, the sharpness of boundaries between traditional regions is not so acute, due to a great level of overlap of part of its biotic elements. PMID- 25112338 TI - A new species of freshwater crab of the genus Microthelphusa Pretzmann, 1968 (Crustacea: Brachyura: Pseudothelphusidae) from the Amazon region of Guyana. AB - A new species of freshwater crab, Microthelphusa furcifer, is described and illustrated from the Potaro-Siparuni Kuribrong River in the Guyana Shield (Amazon region of Guyana). The new species can be easily separated from its congeners by the morphology of the first gonopod. The first gonopod of Microthelphusa meansi Cumberlidge, 2007, is illustrated to clarify some aspects of its morphology. PMID- 25112337 TI - Redescription and distribution of the rare flower chafer, Periphanesthes aurora (Motschulsky, 1858) (Coleoptera: Scarabaeidae: Cetoniinae). AB - This paper includes a detailed redescription of the monotypic genus Periphanesthes Kraatz, 1880 (Coleoptera: Scarabaeidae: Cetoniinae) and its type species, Periphanesthes aurora (Motschulsky, 1858), based on the lectotype (designated within) and additional specimens. Illustrations of external features and parameres are also provided. The distribution of P. aurora is studied, and its new distribution records are mapped. Bonsiella Ruter, 1965 is confirmed as a junior synonym of Periphanesthes Kraatz, 1880. PMID- 25112339 TI - One new species in the cockroach genus Jacobsonina Hebard 1929 (Blattodea, Ectobiidae, Blattellinae) from Mainland China. AB - One new species of Jacobsonina Hebard from China is described and illustrated: Jacobsonina erebis sp. nov.. A key to all known species in this genus, except for J. lugubris (Brunner von Wattenwyl, 1893), based on males, is provided. PMID- 25112340 TI - Re-description of the gudgeon species Saurogobio gracilicaudatus Yao & Yang in Luo, Yue & Chen, 1977 (Teleostei: Cyprinidae) from the Chang-Jiang basin, South China, with a note on its generic classification. AB - Saurogobio gracilicaudatus, originally described from the middle Yangtze River (Chang-Jiang in Chinese) basin at Yichang and Guanghua (now Laohekou), Hubei Province, South China, is here re-described, with particular concern for oromandibular structures in the mouth. It is uniquely distinguishable from all other species of Saurogobio in having a rostral cap with a slightly crenulated median portion, lips covered with brush-like, conical papillae, and a lower lip with a small, smooth and protruded central pad anteriorly free and posteriorly confluent with lateral lobes. The generic classification of this species is also discussed on the basis of oromandibular structures, which are of taxonomic importance in generic classification of gudgeons. PMID- 25112341 TI - A new minute pirate bug of the genus Scoloposcelis (Hemiptera: Heteroptera: Anthocoridae) from West Malaysia. AB - Scoloposcelis seidaii sp. nov. is described from the Malay Peninsula based on a single specimen collected under the bark of a decaying tree. This discovery represents the first distribution record of the genus Scoloposcelis from Malaysia. Habitus photographs and diagnosis of S. parallela (Motschulsky, 1863) are provided for comparison with S. seidaii. PMID- 25112342 TI - Cladocroce caelum sp. nov. from the Brazilian coast; first record of the genus in the South Atlantic. PMID- 25112343 TI - On cockroaches of the subfamily Epilamprinae (Dictyoptera: Blaberidae) from South India and Sri Lanka, with descriptions of new taxa. AB - The new genus Indoapterolampra, gen. nov. and two new species (I. rugosiuscula sp. nov. and Morphna lucida sp. nov.) are described. Rhabdoblatta praecipua (Walker, 1868) is removed from the synonymy with 'Polyzosteria' terranea Walker, 1868. The latter species is considered Epilamprinae gen. sp. The lectotype of Phoraspis (Thorax) porcellana Saussure, 1862 is designated. A key for the genera of Epilamprinae from South India and Sri Lanka is provided. Detailed morphological descriptions of the studied taxa are given. The structure of the male genitalia of I. rugosiuscula sp. nov., M. lucida sp. nov., M. plana (Brunner von Wattenwyl, 1865), M. decolyi (Bolivar, 1897) and R. praecipua and that of the female genital complex of M. decolyi, P. (T.) porcellana and Phlebonotus anomalus (Saussure, 1863) are described for the first time. Some aspects of the cockroach evolution are briefly discussed. PMID- 25112344 TI - An annotated checklist of Lithobiomorpha of China. AB - The lithobiomorph centipede fauna of China is listed here based on literature data. A total of 68 species in 15 genera/subgenera in 2 families, Henicopidae and Lithobiidae, has been recorded from China. Three genera and forty-four species are known only from China, including the monotypic genera Pterygotergum and Hedinobius. The original descriptions of 16 nominal species were based on specimens of single sex only and 13 nominal species of Lithobius have never been allocated to a subgenus. Lithobius (Lithobius) zhui Pei, Ma, Shi, Wu & Gai, 2011 is moved to subgenus Lithobius (Ezembius). Distribution data for each species is provided here to promote further studies on the Lithobiomorpha fauna of China. PMID- 25112345 TI - Rajella paucispinosa n. sp., a new deep-water skate (Elasmobranchii, Rajidae) from the western Indian Ocean off South Mozambique, and a revised generic diagnosis. AB - A new species of the widely in temperate and tropical latitudes distributed skate genus Rajella is described based on an almost adult male specimen from the western Indian Ocean off South Mozambique. The holotype of R. paucispinosa n. sp. was caught during cruise 17 of RV 'Vityaz' along the deep western Indian Ocean in 1988/89. It is the northernmost record of a Rajella specimen in the western Indian Ocean. The new species is the 18th valid species of the genus and the fifth species in the western Indian Ocean. It differs from its congeners in the small maximal total length of about 50 cm and only few thorns on the dorsal surface. The new species has only two thorns on each orbit, one nuchal thorn, one right scapular thorn (left one not detectable, abraded), and one median row of tail thorns. Other species of Rajella typically have half rings of thorns on orbital rims, a triangle of thorns on nape-shoulder region, and at least three rows of tail thorns. Another conspicuous feature of the new species is the almost completely white dorsal and ventral coloration. PMID- 25112347 TI - Fourteen new generic and ten new specific synonymies in Pholcidae (Araneae), and transfer of Mystes Bristowe to Filistatidae. AB - Between 1998 and 2011, the Venezuelan arachnologist Manuel Angel Gonzalez-Sponga (GS) published a series of taxonomic papers devoted to the Pholcidae of Venezuela. Of his 22 new genera, 20 were monotypic when described, suggesting a high percentage of synonyms. We studied his descriptions and as far as accessible his type specimens and propose the following new generic synonymies: Autana GS, 2011 = Mesabolivar GS, 1998; Ayomania GS, 2005 and Venezuela Kocak & Kemal, 2008 (new replacement names for Falconia GS, 2003) = Mecolaesthus Simon, 1893; Carbonaria GS, 2009 = Mecolaesthus Simon, 1893; Caruaya GS, 2011 = Mesabolivar GS, 1998; Coroia GS, 2005 = Artema Walckenaer, 1837; Maimire GS, 2009 = Mecolaesthus Simon, 1893; Moraia GS, 2011 = Mecolaesthus Simon, 1893; Nasuta GS, 2009 = Mecolaesthus Simon, 1893; Portena GS, 2011 = Metagonia Simon, 1893; Rioparaguanus GS, 2005 = Mesabolivar GS, 1998; Tonoro GS, 2009 = Litoporus Simon, 1893; Sanluisi GS, 2003 = Mecolaesthus Simon, 1893. Three of the type species are also specific synonyms: Autana autanensis GS, 2011 = Mesabolivar aurantiacus (Mello-Leitao, 1930); Coroia magna GS, 2005 = Artema atlanta Walckenaer, 1837; Tonoro multispinae GS, 2009 = Litoporus uncatus (Simon, 1893). Six species that Gonzalez-Sponga described under Blechroscelis (a genus previously synonymized with Priscula Simon, 1893) are all synonyms of Mesabolivar eberhardi Huber, 2000 (B. acuoso GS, 2011; B. araguanus GS, 2011; B. blechroscelis GS, 2011; B. copeyensis GS, 2011; B. cordillerano GS, 2011; B. andinensis GS, 2011). In addition, and unrelated to Gonzalez-Sponga's work, we synonymize the Central Asian monotypic genus Ceratopholcus Spassky, 1934 with Crossopriza Simon, 1893; we synonymize the Chinese species Pholcus acerosus Peng & Zhang, 2011 with Pholcus fragillimus Strand, 1907 and remove the Malaysian monotypic genus Mystes Bristowe, 1938, previously thought to be the only East Asian representative of the subfamily Ninetinae, to the family Filistatidae. PMID- 25112346 TI - Taxonomic revision of the semi-aquatic skink Parvoscincus leucospilos (Reptilia: Squamata: Scincidae), with description of three new species. AB - We review the recent discovery of multiple populations of the enigmatic, semi aquatic Sphenomorphus Group skink, Parvoscincus leucospilos Peters, and investigate the morphological and genetic diversity of isolated, allopatric populations of this unique skink. Our investigations support the recognition of four unique evolutionary lineages distributed across Luzon Island in the Philippines, three of which are herein described as new species (P. tikbalangi sp. nov., P. manananggalae sp. nov., and P. duwendorum sp. nov.). All four recognized species are genetically divergent in both mitochondrial and nuclear DNA sequences, and morphologically distinct. The description of three new Luzon Island endemic species adds to the growing body of literature suggesting that mechanisms driving the accumulation of vertebrate diversity in the Philippines may vary regionally across the archipelago. PMID- 25112348 TI - Cymatodera ochlera Barr, a junior synonym of Cymatodera wolcotti Barr, with a comparison to similar species (Coleoptera: Cleridae). AB - Cymatodera ochlera Barr 1972 has been considered to be very similar to but distinct from C. wolcotti Barr 1950. We present evidence to show that these two species are conspecific and C. ochlera should be treated as a junior synonym of C. wolcotti. Cymatodera wolcotti is compared to C. balteata and C. undulata, two species remarkably similar to C. wolcotti. Morphological characters of significant value are presented that confirm C. balteata and C. undulata are separate species. Images of all characters discussed are provided. PMID- 25112349 TI - Two new species and a new synonym of the genus Paederus Fabricius (Coleoptera: Staphylinidae: Paederinae) from China. AB - Two new species of the genus Paederus Fabricius, 1775 from mainland China are described: Paederus (Harpopaederus) brevior sp. nov. (Shaanxi) and P. (H.) multidenticulatus sp. nov. (Hubei). One new synonym is proposed: Paederus parvidenticulatus Li, Zhou & Solodovnikov, 2013 = Paederus symmetricus Li, Zhou & Solodovnikov, 2013 syn. nov. PMID- 25112350 TI - Nippontonia ashmoreiensis sp. nov., (Crustacea: Decapoda; Pontoniinae) from Ashmore Reef, Western Australia. AB - An undescribed species of pontoniine shrimp of the genus Nippontonia Bruce & Bauer, N. ashmoriensis sp. nov., collected from a sponge from Ashmore Reef, Western Australia, is described and illustrated. PMID- 25112351 TI - Helicopsyche (Feropsyche) timbira sp. nov. (Trichoptera: Helicopsychidae), a new species from southeastern Brazil. PMID- 25112352 TI - Aphodius petri: a replacement name for the primary junior homonym Aphodius kozlovi Frolov, 2009 (Coleoptera: Scarabaeidae: Aphodiinae). PMID- 25112353 TI - Galkinius nom.nov., replacement name for Galkinia Ross & Newman, 1995. PMID- 25112354 TI - Plume moths of Malawi (Lepidoptera: Pterophoridae). AB - A review of Pterophoridae of Malawi is presented; 96 species from 35 genera and five subfamilies are recorded. Fourteen species are described as new: Agdistis nyasa Kovtunovich & Ustjuzhanin sp. nov., Platyptilia mugesse Kovtunovich & Ustjuzhanin sp. nov., Stenoptilia juniper Kovtunovich & Ustjuzhanin sp. nov., Sphenarches mulanje Kovtunovich & Ustjuzhanin sp.nov., Marasmarcha lamborni Kovtunovich & Ustjuzhanin sp. nov., Arcoptilia malawica Kovtunovich & Ustjuzhanin sp. nov., Apoxyptilus uzumarus Kovtunovich & Ustjuzhanin sp. nov., Gypsochares murphy Kovtunovich & Ustjuzhanin sp. nov., Crassuncus livingstoni Kovtunovich & Ustjuzhanin sp. nov., Hellinsia namizimu Kovtunovich & Ustjuzhanin sp. nov., Hellinsia shewa Kovtunovich & Ustjuzhanin sp. nov., Picardia leza Kovtunovich & Ustjuzhanin sp. nov., Picardia raymondi Kovtunovich & Ustjuzhanin sp. nov., Picardia tumbuka Kovtunovich & Ustjuzhanin sp. nov. New synonymies are established for 10 species: Deuterocopus deltoptilus Meyrick, 1930 = Deuterocopus socotranus Rebel, 1907 syn. nov.; Deuterocopus henrioti Bigot & Boireau, 2006 = Deuterocopus socotranus Rebel, 1907 syn. nov.; Platyptilia periacta Meyrick, 1910 = Platyptilia farfarella Zeller, 1867 syn. nov.; Platyptilia claripicta Fletcher, 1910 = Platyptilia farfarella Zeller, 1867 syn. nov.; Platyptilia pygmaeana Strand, 1913 = Sphenarches anisodactylus (Walker, 1864) syn. nov.; Exelastis bergeri Bigot, 1969 = Exelastis crudipennis (Meyrick, 1932) syn. nov.; Prichotilus tanzanicus Gielis, 2011 = Prichotilus tara Ustjuzhanin and Kovtunovich, 2011 syn. nov.; Crassuncus chappuisi Gibeaux, 1994 = Crassuncus ecstaticus (Meyrick, 1932) syn. nov.; Paulianilus lolibai Arenberger, 2011 = Hellinsia madecasseus (Bigot, 1964) syn. nov.; Pterophorus purus Meyrick, 1913 = Crassuncus pacifica (Meyrick, 1911) syn. nov. New combinations are established for six species: Marasmarcha bengtssoni (Gielis, 2009) comb. nov.; Marasmarcha locharcha (Meyrick, 1924) comb. nov.; Marasmarcha rubriacuta (Gielis, 2009) comb. nov.; Procapperia insomnis (Townsend, 1956) comb. nov.; Crassuncus ecstaticus (Meyrick, 1932) comb. nov.; Crassuncus colubratus (Meyrick, 1909) comb. nov. For Stenoptilia viettei Gibeaux, 1994, Sphenarches bifurcatus Gielis, 2009, Crassuncus ecstaticus (Meyrick, 1932) images of the male genitalia are presented for the first time, for Marasmarcha bengtssoni (Gielis, 2009), and Stenodacma cognata Gielis, 2009 female genitalia are illustrated for the first time. Species of wide pantropical or cosmopolitan distribution are not reported as new for the fauna of Malawi. However, 65 species of Pterophoridae are reported for the fauna of Malawi for the first time. One of them, Stenoptilia viettei Gibeaux, 1994, described from Madagascar, is reported for continental Africa for the first time. PMID- 25112355 TI - The identity of the treehopper genus Dysyncritus Fowler, with descriptions of new related taxa (Hemiptera: Membracidae: Heteronotinae). AB - Dysyncritus Fowler is revised based on the examination of primary types, and restructured to exclusively accomodate Dysyncritus intectus Fowler, 1895. Allodrilus Evangelista gen. nov. (type species: Cymbomorpha nitidipennis Funkhouser, 1922 = Allodrilus nitidipennis (Funkhouser, 1922) comb. nov.) is erected with seven newly discovered taxa: A. alboferrugineus Evangelista sp. nov. (Brazil, Colombia, Guyana), A. colombiensis Florez-V sp. nov. (Colombia), A. deitzi Evangelista sp. nov. (Ecuador), A. granulatus Evangelista sp. nov. (Ecuador), A. horizontalis Evangelista sp. nov. (Bolivia), A. intermedius Evangelista sp. nov. (Ecuador), and A. similis Evangelista sp. nov. (Peru). A key to males is provided, in addition to annotated descriptions and illustrations. Nomenclatural changes are proposed to species formerly included in Dysyncritus: Smiliorachis nubilis (Goding, 1930) comb. nov., Smiliorachis discrepans (Goding, 1930) comb. nov., and Dysyncritus lineatus Goding, 1930 (= Smiliorachis octilinea Stal, 1869 syn. nov.). PMID- 25112356 TI - Two new species of Cosmolaelaps Berlese (Acari:Laelapidae) from Iran . AB - This paper reports on two species of mites of the genus Cosmolaelaps Berlese, 1903 in Iran--C. dorfakiensis sp. nov., and C. pinnatus sp. nov., extracted from soil and leaf litter samples in Guilan Province, Northern Iran. A key to the species of Cosmolaelaps occurring in the Iran is also provided. PMID- 25112357 TI - Three new bee species of Rhophitulus Ducke (Hymenoptera, Apidae, Protandrenini) from Argentina and Brazil. AB - This work describes three newly discovered species of Rhophitulus Ducke, 1907: R. labiosus n. sp. from Minas Gerais (Brazil), R. mimus n. sp. from Salta (Argentina), and R. xenopalpus n. sp. from Catamarca and Tucuman (Argentina). Photographs of the holotype of Rhophitulus steinbachi (Friese, 1916) are provided, and modifications in the morphology of a female of R. xenopalpus n. sp. when parasitized by Strepsiptera are recorded for the first time for the genus. PMID- 25112358 TI - The first record of an association between a pontoniine shrimp (Crustacea: Decapoda: Palaemonidae: Pontoniinae) and a thalassematid spoon worm (Echiura: Thalassematidae), with the description of a new shrimp species. AB - A new pontoniine shrimp species, Eupontonia nudirostris sp. nov. (Crustacea: Decapoda: Palaemonidae: Pontoniinae), was found in association with the thalassematid spoon worm Listriolobus sp. (Echiura: Thalassematidae) in the mangrove littoral of Dam Bay of Tre Island, Nhatrang Bay, Vietnam. This is the first record of an association between symbiotic pontoniine shrimp and spoon worm as their host. The new shrimp species clearly differs from other representatives of the genus Eupontonia Bruce, 1971 by the unarmed rostrum with a blunt tip and the reduced antennal tooth on the carapace, which can be considered as an adaptation to symbiotic lifestyle inside cramped burrows of the host. A revised key to the genus Eupontonia Bruce, 1971 is presented. PMID- 25112359 TI - Two new species of Cyta (Acari: Prostigmata: Bdellidae) from Western Iran . AB - This paper reports two new species of Bdellidae, Cyta leliae sp. nov. and Cyta kurdistanicus sp. nov., collected from soil and litter under oak trees, Quercus brantii Lindl. (Fagaceae), wild almond, Amygdalus lycioides Spach (Rosaceae) and grass, Kurdistan Province, Iran. A key is provided to adult female Cyta of the world. PMID- 25112360 TI - Swedish Plectida (Nematoda). Part 7. Setostephanolaimus tchesunovi sp. n. from the west coast of Sweden. AB - A new species of Setostephanolaimus, S. tchesunovi sp. n., is described from bottom sediments collected in the Skagerrak and Gullmarn Fjord off the west coast of Sweden. It is characterised by 1.0-1.3 mm long body, outer labial setae 6.5 8.5 um long, cephalic setae 9-11 um long, subcephalic setae 4-6 um long, transversely-oval amphid, female with monodelphic opisthodelphic reproductive system, male with 6-9 tubular and without alveolar supplements, spicules arcuate and 54-64 um long, gubernaculum with dorsal apophysis. A tabular compendium and dichotomous identification key to species of the genus Setostephanolaimus are provided. PMID- 25112361 TI - A fossil Paratrombiinae mite (Actinotrichida: Trombidioidea) from the Rovno amber, Ukraine. AB - The first description of a fossil representative of Paratrombiinae from the Rovno amber, Paratrombium rovniense sp. nov., based on an unengorged larva, is provided. The discovery results in a re-definition of the Paratrombiinae and of Paratrombium, which also comprise species with two pectinalae on coxa I. PMID- 25112362 TI - A new species of Petersitocoroides Brailovsky (Hemiptera: Heteroptera: Coreidae: Coreini) from Peru. AB - Petersitocoroides vergarae, a new species from Peru, is described and placed in the tribe Coreini (Heteroptera). Dorsal illustrations and drawings of the pronotum, head and male genitalia, as well as a key to the known species, are provided. PMID- 25112363 TI - A new species of the genus Mazaeras Walker, 1855 (Lepidoptera: Erebidae: Arctiinae). PMID- 25112364 TI - Decoration of silicon nanostructures with copper particles for simultaneous selective capture and mass spectrometry detection of His-tagged model peptide. AB - We present in this work a simple and fast preparation method of a new affinity surface-assisted laser/desorption ionization mass spectrometry (SALDI-MS) substrate based on silicon nanostructures decorated with copper particles. The silicon nanostructures were fabricated by the metal-assisted chemical etching (MACE) method. Then, superhydrophilic areas surrounded by superhydrophobic regions were formed through hydrosilylation reaction of 1-octadecene, followed by local degradation of the octadecyl layer. After that, copper particles were deposited in the hydrophilic areas by using the electroless method. We have demonstrated that these surfaces were able to perform high selective capture of model His-tag peptide even in a complex mixture such as serum solution. Then, the captured peptide was detected by mass spectrometry at a femtomolar level without the need of organic matrix. PMID- 25112365 TI - Protein S-glutathionylation: from current basics to targeted modifications. AB - The interaction between antioxidant glutathione and the free thiol in susceptible cysteine residues of proteins leads to reversible protein S-glutathionylation. This reaction ensures cellular homeostasis control (as a common redox-dependent post-translational modification associated with signal transduction) and intervenes in oxidative stress-related cardiovascular pathology (as initiated by redox imbalance). The purpose of this review is to evaluate the recent knowledge on protein S-glutathionylation in terms of chemistry, broad cellular intervention, specific quantification, and potential for therapeutic exploitation. The data bases searched were Medline and PubMed, from 2009 to 2014 (term: glutathionylation). Protein S-glutathionylation ensures protection of protein thiols against irreversible over-oxidation, operates as a biological redox switch in both cell survival (influencing kinases and protein phosphatases pathways) and cell death (by potentiation of apoptosis), and cross-talks with phosphorylation and with S-nitrosylation. Collectively, protein S glutathionylation appears as a valuable biomarker for oxidative stress, with potential for translation into novel therapeutic strategies. PMID- 25112367 TI - The evolution of boosting algorithms. From machine learning to statistical modelling. AB - BACKGROUND: The concept of boosting emerged from the field of machine learning. The basic idea is to boost the accuracy of a weak classifying tool by combining various instances into a more accurate prediction. This general concept was later adapted to the field of statistical modelling. Nowadays, boosting algorithms are often applied to estimate and select predictor effects in statistical regression models. OBJECTIVES: This review article attempts to highlight the evolution of boosting algorithms from machine learning to statistical modelling. METHODS: We describe the AdaBoost algorithm for classification as well as the two most prominent statistical boosting approaches, gradient boosting and likelihood-based boosting for statistical modelling. We highlight the methodological background and present the most common software implementations. RESULTS: Although gradient boosting and likelihood-based boosting are typically treated separately in the literature, they share the same methodological roots and follow the same fundamental concepts. Compared to the initial machine learning algorithms, which must be seen as black-box prediction schemes, they result in statistical models with a straight-forward interpretation. CONCLUSIONS: Statistical boosting algorithms have gained substantial interest during the last decade and offer a variety of options to address important research questions in modern biomedicine. PMID- 25112369 TI - Electronic structures and selective fluoride sensing features of Os(bpy)2(HL(2-)) and [{Os(bpy)2}2(MU-HL(2-))](2+) (H3L: 5-(1H-benzo[d]imidazol-2-yl)-1H-imidazole 4-carboxylic acid). AB - The article deals with the newly designed mononuclear and asymmetric dinuclear osmium(ii) complexes Os(II)(bpy)2(HL(2-)) (1) and [(bpy)2Os(II)(MU-HL(2 ))Os(II)(bpy)2](Cl)2 ([2](Cl)2)/[(bpy)2Os(II)(MU-HL(2-))Os(II)(bpy)2](ClO4)2 ([2](ClO4)2), respectively, (H3L = 5-(1H-benzo[d]imidazol-2-yl)-1H-imidazole-4 carboxylic acid and bpy = 2,2'-bipyridine). The identity of 1 has been established by its single crystal X-ray structure. The ligand (HL(2-))-based primary oxidation process (E, 0.23 V versus SCE) along with the partial metal contribution (~20%) in 1 has been revealed by the ligand-dominated HOMO of 1 (HL(2-): 88%, Os: 8%), as well as by the Mulliken spin density distribution of 1(+) (HL(2-): 0.878, Os: 0.220). Accordingly, 1(+) exhibits a free radical type EPR at 77 K with a partial metal-based anisotropic feature (g1 = 2.127, g2 = 2.096, g3 = 2.046; = 2.089; Deltag = 0.08). (1)H-NMR of the dinuclear 2(2+) in CDCl3 suggests an intimate mixture of two diastereomeric forms in a 1 : 1 ratio. The DFT-supported predominantly Os(ii)/Os(iii)-based couples of asymmetric 2(2+) at 0.24 V and 0.50 V versus SCE result in a comproportionation constant (Kc) value of 8.2 * 10(4). The class I mixed valent state of 2(3+) (S = 1/2) has, however, been corroborated by the Mulliken spin density distribution of Os1: 0.887, Os2: 0.005, HL(2-): 0.117, as well as by the absence of a low-energy IVCT (intervalence charge transfer) band in the near-IR region (up to 2000 nm). The appreciable spin accumulation on the bridge in 2(3+) or 2(4+) (S = 1, Os1: 0.915, Os2: 0.811 and HL(2-): 0.275) implies a mixed electronic structural form of [(bpy)2Os(III)(MU-HL(2-))Os(II)(bpy)2](3+)(major)/[(bpy)2Os(II)(MU-HL( ))Os(II)(bpy)2](3+)(minor) or [(bpy)2Os(III)(MU-HL(2 ))Os(III)(bpy)2](4+)(major)/[(bpy)2Os(III)(MU-HL(-))Os(II)(bpy)2](4+) (minor), respectively. The mixed valent {Os(III)(MU-HL(2-))Os(II)} state in 2(3+), however, fails to show EPR at 77 K due to the rapid spin relaxation process. The DFT-supported bpy-based two reductions for both 1(+) and 2(2+) appear in the potential range of -1.5 V to -1.8 V versus SCE. The electronic transitions in 1(n) and 2(n) are assigned by the TD-DFT calculations. Furthermore, the potential anion sensing features of 1 and 2(2+)via the involvement of the available N-H proton in the framework of coordinated HL(2-) have been evaluated by different experimental investigations, in conjunction with the DFT calculations, using a wide variety of anions such as F(-), Cl(-), Br(-), I(-), OAc(-), SCN(-), HSO4(-) and H2PO4(-). This, however, establishes that both 1 and 2(2+) are equally efficient in recognising the F(-) ion selectively, with log K values of 6.83 and 5.89, respectively. PMID- 25112368 TI - Globalization of leptospirosis through travel and migration. AB - Leptospirosis remains the most widespread zoonotic disease in the world, commonly found in tropical or temperate climates. While previous studies have offered insight into intra-national and intra-regional transmission, few have analyzed transmission across international borders. Our review aimed at examining the impact of human travel and migration on the re-emergence of Leptospirosis. Results suggest that alongside regional environmental and occupational exposure, international travel now constitute a major independent risk factor for disease acquisition. Contribution of travel associated leptospirosis to total caseload is as high as 41.7% in some countries. In countries where longitudinal data is available, a clear increase of proportion of travel-associated leptospirosis over the time is noted. Reporting patterns is clearly showing a gross underestimation of this disease due to lack of diagnostic facilities. The rise in global travel and eco-tourism has led to dramatic changes in the epidemiology of Leptospirosis. We explore the obstacles to prevention, screening and diagnosis of Leptopirosis in health systems of endemic countries and of the returning migrant or traveler. We highlight the need for developing guidelines and preventive strategies of Leptospirosis related to travel and migration, including enhancing awareness of the disease among health professionals in high-income countries. PMID- 25112370 TI - Characteristics of evodiamine-exerted stimulatory effects on rat jejunal contractility. AB - This study was designed to characterise the effects of evodiamine on intestinal contractility and reveal the correlated mechanisms. Evodiamine (2.5-80.0 MUM) increased normal jejunal contractility and jejunal hypocontractility established under a variety of experimental conditions. Evodiamine-exerted stimulatory effects were blocked by the L-type Ca(2+) channel blocker nifedipine or abolished in the Ca(2+)-free assay condition. The stimulatory effects of evodiamine on jejunal contractility were partially blocked in the presence of neurotoxin tetrodotoxin or endogenous acetylcholine synthesis blocker hemicholinium-3 or muscarinic receptor antagonist atropine, respectively. Evodiamine-exerted stimulatory effects were blocked by c-kit receptor tyrosine kinase inhibitor imatinib. Evodiamine increased myosin phosphorylation in jejunal smooth muscle of constipation-prominent rats. These results showed that evodiamine-exerted stimulatory effects on jejunal segments are Ca(2+)-dependent, need the presence of interstitial cell of Cajal, requirement of cholinergic neuron and correlate with increased myosin phosphorylation, implicating the potential value of evodiamine in relieving hypo-motility disorders. PMID- 25112371 TI - A retrospective study of short- and long-term effects on renal function after acute renal infarction. AB - PURPOSE: Acute renal infarction is often missed or diagnosed late due to its rarity and non-specific clinical manifestations. This study analyzed the clinical and laboratory findings of patients diagnosed with renal infarction to determine whether it affects short- or long-term renal prognosis. METHODS: We retrospectively reviewed the medical records of 100 patients diagnosed as acute renal infarction from January 1995 to September 2012 at Gyeongsang National University Hospital, Jinju, South Korea. RESULTS: Acute kidney injury (AKI) occurred in 30 patients. Infarct size was positively correlated with the occurrence of AKI (p = 0.004). Compared with non-AKI patients, AKI occurrence was significantly correlated with degree of proteinuria (p < 0.001) and the presence of microscopic hematuria (p = 0.035). AKI patients had higher levels of aspartate transaminase (p < 0.001), alanine transaminase (p < 0.001), and lactated dehydrogenase (p = 0.027). AKI after acute renal infarction was more common in patients with chronic renal failure (CRF) (eGFR < 60 mL/min), compared with non CRF patients, whose baseline eGFR was >60 mL/min (p = 0.003). Most patients recovered from AKI, except for seven patients (7%) who developed persistent renal impairment (chronic kidney disease progression) closely correlated with magnitude of infarct size (p = 0.015). Six AKI patients died due to combined comorbidity. CONCLUSIONS: AKI is often associated with acute renal infarction. Although most AKI recovers spontaneously, renal impairment following acute renal infarction can persist. Thus, early diagnosis and intervention are needed to preserve renal function. PMID- 25112372 TI - The influence of vitamin D analogs on calcification modulators, N-terminal pro-B type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study. AB - BACKGROUND: The risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined. METHODS: In 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin A, NT-proBNP, hs-Crp, IL-6 and TNF-alpha, during 16 weeks of treatment. RESULTS: NT-proBNP and osteoprotegerin increased comparably in the paricalcitol and alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol treated group compared with the paricalcitol-treated group (difference 32.84 MUmol/l (95% C.I.; range 0.21-67.47)) during the first treatment period. No difference was found between the groups during the second treatment period, and IL-6, TNF-alpha and hs-Crp were unchanged in both treatment groups. CONCLUSIONS: Paricalcitol and alfacalcidol modulate regulators of vascular calcification. Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We did not find any anti-inflammatory effect or difference in changes of NT-proBNP. TRIAL REGISTRY: ClinicalTrials.gov NCT00469599 May 3 2007. PMID- 25112375 TI - A distinct immunogenic region of glutamic acid decarboxylase 65 is naturally processed and presented by human islet cells to cytotoxic CD8 T cells. AB - CD8 T cells specific for islet autoantigens are major effectors of beta cell damage in type 1 diabetes, and measurement of their number and functional characteristics in blood represent potentially important disease biomarkers. CD8 T cell reactivity against glutamic acid decarboxylase 65 (GAD65) in HLA-A*0201 subjects has been reported to focus on an immunogenic region 114-123 (VMNILLQYVV), with studies demonstrating both 114-123 and 114-122 epitopes being targeted. However, the fine specificity of this response is unclear and the key question as to which epitope(s) beta cells naturally process and present and, therefore, the pathogenic potential of CD8 T cells with different specificities within this region has not been addressed. We generated human leucocyte antigen (HLA)-A*0201-restricted CD8 T cell clones recognizing either 114-122 alone or both 114-122 and 114-123. Both clone types show potent and comparable effector functions (cytokine and chemokine secretion) and killing of indicator target cells externally pulsed with cognate peptide. However, only clones recognizing 114-123 kill target cells transfected with HLA-A*0201 and GAD2 and HLA-A*0201(+) human islet cells. We conclude that the endogenous pathway of antigen processing by HLA-A*0201-expressing cells generates GAD65114-123 as the predominant epitope in this region. These studies highlight the importance of understanding beta cell epitope presentation in the design of immune monitoring for potentially pathogenic CD8 T cells. PMID- 25112373 TI - New subfamilies of major intrinsic proteins in fungi suggest novel transport properties in fungal channels: implications for the host-fungal interactions. AB - BACKGROUND: Aquaporins (AQPs) and aquaglyceroporins (AQGPs) belong to the superfamily of Major Intrinsic Proteins (MIPs) and are involved in the transport of water and neutral solutes across the membranes. MIP channels play significant role in plant-fungi symbiotic relationship and are believed to be important in host-pathogen interactions in human fungal diseases. In plants, at least five major MIP subfamilies have been identified. Fungal MIP subfamilies include orthodox aquaporins and five subgroups within aquaglyceroporins. XIP subfamily is common to both plants and fungi. In this study, we have investigated the extent of diversity in fungal MIPs and explored further evolutionary relationships with the plant MIP counterparts. RESULTS: We have extensively analyzed the available fungal genomes and examined nearly 400 fungal MIPs. Phylogenetic analysis and homology modeling exhibit the existence of a new MIP cluster distinct from any of the known fungal MIP subfamilies. All members of this cluster are found in microsporidia which are unicellular fungal parasites. Members of this family are small in size, charged and have hydrophobic residues in the aromatic/arginine selectivity filter and these features are shared by small and basic intrinsic proteins (SIPs), one of the plant MIP subfamilies. We have also found two new subfamilies (delta and gamma2) within the AQGP group. Fungal AQGPs are the most diverse and possess the largest number of subgroups. We have also identified distinguishing features in loops E and D in the newly identified subfamilies indicating their possible role in channel transport and gating. CONCLUSIONS: Fungal SIP-like MIP family is distinct from any of the known fungal MIP families including orthodox aquaporins and aquaglyceroporins. After XIPs, this is the second MIP subfamily from fungi that may have possible evolutionary link with a plant MIP subfamily. AQGPs in fungi are more diverse and possess the largest number of subgroups. The aromatic/arginine selectivity filter of SIP-like fungal MIPs and the delta AQGPs are unique, hydrophobic in nature and are likely to transport novel hydrophobic solutes. They can be attractive targets for developing anti-fungal drugs. The evolutionary pattern shared with their plant counterparts indicates possible involvement of new fungal MIPs in plant-fungi symbiosis and host-pathogen interactions. PMID- 25112374 TI - Features of the built environment related to physical activity friendliness and children's obesity and other risk factors. AB - OBJECTIVES: We investigated the relationships among environmental features of physical activity friendliness, socioeconomic indicators, and prevalence of obesity (BMI status), central adiposity (waist circumference, waist-height ratio), and hypertension. DESIGN AND SAMPLE: The design was cross-sectional; the study was correlational. The sample was 911 kindergarteners through sixth graders from three schools in an urban school district residing in 13 designated neighborhoods. MEASURES: Data from walking environmental community audits, census data for socioeconomic indicators, body mass index, waist circumference, waist height ratio, and blood pressure were analyzed. A modified Alfonzo's Hierarchy of Walking Needs model was the conceptual framework for environmental features (i.e., accessibility, safety, comfort, and pleasurability) related to physical activity. RESULTS: Accessibility was significantly and negatively correlated with prevalence of obesity and with prevalence of a waist-height ratio >0.50. When neighborhood education was controlled, and when both neighborhood education and poverty were controlled with partial correlational analysis, comfort features of a walking environment were significantly and positively related to prevalence of obesity. When poverty was controlled with partial correlation, accessibility was significantly and negatively correlated with prevalence of waist-height ratio >0.50. CONCLUSIONS: The built environment merits further research to promote physical activity and stem the obesity epidemic in children. Our approach can be a useful framework for future research. PMID- 25112377 TI - Variants associated with type 2 diabetes identified by the transethnic meta analysis study: assessment in American Indians and evidence for a new signal in LPP. AB - AIM/HYPOTHESIS: A recent genome-wide trans-ancestry meta-analysis identified seven new loci associated with type 2 diabetes. We assessed the replication of the seven lead single nucleotide polymorphisms (SNPs) and evaluated these loci for additional signals in American Indians. METHODS: Seven SNPs were genotyped in 7,710 individuals from a longitudinally studied American Indian population, and associations with type 2 diabetes, BMI and related phenotypes were assessed. Previous genome-wide association study (GWAS) data from these individuals were used to screen for additional type 2 diabetes signals at these loci. A variant independent of the trans-ancestry meta-analysis was identified within LPP, and its replication was assessed in an additional 3,106 urban American Indians. RESULTS: SNP rs6813195 near to TMEM154 was nominally associated with type 2 diabetes (p = 0.01, OR 1.12 [95% CI 1.03, 1.22]) and adiposity: the type 2 diabetes risk allele was associated with a lower percentage body fat (beta = 1.451%, p = 4.8 * 10(-4)). Another SNP, rs3130501 near to POU5F1-TCF19, was associated with BMI (beta = -0.012, p = 0.004), type 2 diabetes adjusted for BMI (p = 0.02, OR 1.11 [95% CI 1.02, 1.22]), 2 h glucose concentrations (beta = 0.080 mmol/l, p = 0.02) and insulin resistance estimated by homeostatic model (beta = 0.039, p = 0.009). The independent variant identified at the LPP locus in our American Indian GWAS for type 2 diabetes was replicated in the additional samples (all American Indian meta-analysis, p = 8.9 * 10(-6), OR 1.29 [95% CI 1.15, 1.45]). CONCLUSIONS/INTERPRETATION: For two of the seven newly identified variants, there was nominal evidence for association with type 2 diabetes and related traits in American Indians. Identification of an independent variant at the LPP locus suggests the existence of more than one type 2 diabetes signal at this locus. PMID- 25112376 TI - RANKL-OPG and RAGE modulation in vascular calcification and diabetes: novel targets for therapy. AB - Type 2 diabetes is associated with increased cardiovascular morbidity and mortality and early vascular ageing. This takes the form of atherosclerosis, with progressive vascular calcification being a major complication in the pathogenesis of this disease. Current research and drug targets in diabetes have hitherto focused on atherosclerosis, but vascular calcification is now recognised as an independent predictor of cardiovascular morbidity and mortality. An emerging regulatory pathway for vascular calcification in diabetes involves the receptor activator for nuclear factor kappaB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). Important novel biomarkers of calcification are related to levels of glycation and inflammation in diabetes. Several therapeutic strategies could have advantageous effects on the vasculature in patients with diabetes, including targeting the RANKL and receptor for AGE (RAGE) signalling pathways, since there has been little success-at least in macrovascular outcomes-with conventional glucose-lowering therapy. There is substantial and relevant clinical and basic science evidence to suggest that modulating RANKL-RANK-OPG signalling, RAGE signalling and the associated proinflammatory milieu alters the natural course of cardiovascular complications and outcomes in people with diabetes. However, further research is critically needed to understand the precise mechanisms underpinning these pathways, in order to translate the anti calcification strategies into patient benefit. PMID- 25112378 TI - The effects of UV-B radiation intensity on biochemical parameters and active ingredients in flowers of Qi chrysanthemum and Huai chrysanthemum. AB - The article studied UV-B effects on biochemical parameters and active ingredients in flowers of Qi chrysanthemum and Huai chrysanthemum during the bud stage. The experiment included four UV-B radiation levels (CK, ambient UV-B; T1, T2 and T3 indicated a 5%, 10% and 15% increase in ambient UV-BBE, respectively) to determine the optimal UV-B radiation intensity in regulating active ingredients level in flowers of two chrysanthemum varieties. Flower dry weight of two cultivars was not affected by UV-B radiation under experimental conditions reported here. UV-B treatments significantly increased the rate of superoxide radical production, hydrogen peroxide (H2O2) (except for T1) and malondialdehyde concentration in flowers of Huai chrysanthemum and H2O2 concentration in flowers of Qi chrysanthemum. T2 and T3 treatments induced a significant increase in phenylalanine ammonia lyase enzyme (PAL) activity, anthocyanins, proline, ascorbic acid, chlorogenic acid and flavone content in flowers of two chrysanthemum varieties, and there were no significant differences in PAL activity, ascorbic acid, flavone and chlorogenic acid content between the two treatments. These results indicated that appropriate UV-B radiation intensity did not result in the decrease in flower yield, and could regulate PAL activity and increase active ingredients content in flowers of two chrysanthemum varieties. PMID- 25112379 TI - Genetics: New molecular classification of gastric adenocarcinoma proposed by The Cancer Genome Atlas. PMID- 25112381 TI - Herniated gravid uterus growing in an incisional hernia: study of three cases. PMID- 25112382 TI - Gentamicin for prevention of intraoperative mesh contamination: demonstration of high bactericide effect (in vitro) and low systemic bioavailability (in vivo). AB - INTRODUCTION: Mesh infection is a severe complication after incisional hernia repair and occurs in 1-3 % of all open mesh implantations. For this reason, topical antimicrobial agent applied directly to the mesh is often used procedure. So far, however, this procedure lacks a scientific basis. MATERIALS AND METHODS: Two different meshes (ParietexTM, Covidien; UltraproTM, Ethicon Johnson & Johnson) were incubated with increasing amounts of three different Staphylococcus aureus strains (ATCC 25923; Mu50; ST239) with or without gentamicin and growth ability were determined in vitro. To further address the question of the systemic impact of topic gentamicin, serum levels were analyzed 6 and 24 h after implantation of gentamicin-impregnated multifilament meshes in 19 patients. RESULTS: None of the gentamicin-impregnated meshes showed any bacterial growth in vitro. This effect was independent of the mesh type for all the tested S. aureus strains. In the clinical setting, serum gentamicin levels 6 h after implantation of the gentamicin-impregnated meshes were below the through-level (range 0.4-2.9 mg/l, mean 1.2 +/- 0.7 mg/l). After 24 h the gentamicin serum levels in all patients had declined 90-65 % of the 6 h values. CONCLUSION: Local application of gentamicin to meshes can completely prevent the growth of even gentamicin resistant S. aureus strains in vitro. The systemic relevance of gentamicin in the clinical controls showed to be very low, without reaching therapeutic concentrations. PMID- 25112380 TI - Tracking and quantification of dendritic cell migration and antigen trafficking between the skin and lymph nodes. AB - Skin-derived dendritic cells (DCs) play a crucial role in the maintenance of immune homeostasis due to their role in antigen trafficking from the skin to the draining lymph nodes (dLNs). To quantify the spatiotemporal regulation of skin derived DCs in vivo, we generated knock-in mice expressing the photoconvertible fluorescent protein KikGR. By exposing the skin or dLN of these mice to violet light, we were able to label and track the migration and turnover of endogenous skin-derived DCs. Langerhans cells and CD103(+)DCs, including Langerin(+)CD103(+)dermal DCs (DDCs), remained in the dLN for 4-4.5 days after migration from the skin, while CD103(-)DDCs persisted for only two days. Application of a skin irritant (chemical stress) induced a transient >10-fold increase in CD103(-)DDC migration from the skin to the dLN. Tape stripping (mechanical injury) induced a long-lasting four-fold increase in CD103(-)DDC migration to the dLN and accelerated the trafficking of exogenous protein antigens by these cells. Both stresses increased the turnover of CD103(-)DDCs within the dLN, causing these cells to die within one day of arrival. Therefore, CD103(-)DDCs act as sentinels against skin invasion that respond with increased cellular migration and antigen trafficking from the skin to the dLNs. PMID- 25112383 TI - A detailed analysis of outcome reporting from randomised controlled trials and meta-analyses of inguinal hernia repair. AB - INTRODUCTION: Evidence is needed to justify whether investment in an internationally agreed core outcome set for inguinal hernia surgery is needed. This study aimed to assess outcome reporting from randomised controlled trials (RCTs) and meta-analyses in inguinal hernia surgery. METHODS: RCTs and meta analyses comparing surgical technique or mesh type for primary inguinal hernia repair were systematically identified. Verbatim details, type, frequency and definition of clinician-observed and -assessed outcomes were summarised. Patient reported outcome measures (PROMs) were analysed for instrument validity and frequency of domain reporting. RESULTS: 40 RCTs (10,810 patients) and 7 meta analyses (17,280 patients) were identified. No single PROM was reported by all studies. There were 58 different clinician-observed outcomes, with recurrence (n = 47, 100%), wound infection (n = 33, 70.2%), haematoma (n = 31, 77.5%) and seroma formation (n = 22, 46.8%) being most frequently reported. All studies measured patients' views, although only 12 (30.0%) used validated instruments. The SF36 was the most commonly used multi-dimensional valid PROM (n = 7), and a visual analogue scale assessing pain (n = 32) was the most frequently used unidimensional scale. Non-validated questionnaires assessed 25 other aspects of patients' health. Two meta-analyses defined recurrence and three chronic pain although neither ensured that included RCTs adhered to the definitions. CONCLUSIONS: Outcome reporting from RCTs concerning inguinal hernia repair is inconsistent and poorly defined, limiting meta-analyses, which themselves do not control for the differing definitions of assessed outcomes. This study justifies investment in a standardised core outcome set for inguinal hernia surgery, to improve outcome reporting and evidence synthesis. PMID- 25112384 TI - Small bowel obstruction after TAPP repair caused by a self-anchoring barbed suture device for peritoneal closure: case report and review of the literature. AB - INTRODUCTION: Transabdominal preperitoneal hernioplasty (TAPP) is a common procedure for groin hernia repair in adults. The peritoneal closure after mesh placement can be performed in various ways. In any case, thorough closure is recommended to avoid mesh exposure to the viscera with the risk of adhesions and bowel incarceration into peritoneal defects. Postoperative intestinal obstructions can mainly occur due to adhesions or bowel herniation through peritoneal defects into the dissected preperitoneal space. Incarcerations can also occur as a consequence of trocar site herniation. RESULTS AND CONCLUSION: Recently barbed self-anchoring knotless suturing devices are frequently used for peritoneal closure. The correct handling of such sutures is crucial to avoid potential complications. Despite of accurate management, bowel adherence and injuries or volvulus can occur. METHODS: We present an unusual case of a postoperative small bowel obstruction owing to strained adhesions and ingrowth between a small bowel segment and a polyglyconate unidirectional self-anchoring barbed suture device. Medline and PudMed databases were searched using the below mentioned keywords and the literature on efficacy and safety of barbed sutures for peritoneal closure is reviewed as well as the usage of such devices in other fields of surgery. PMID- 25112386 TI - Sportsman's groin: reaching a consensus. PMID- 25112385 TI - Parastomal hernia repair with a 3-D mesh device and additional flat mesh repair of the abdominal wall. AB - PURPOSE: Parastomal hernias (PSHs) have been a major clinical problem. The aim of this study was to evaluate a new method of PSH repair in combination with an additional flat mesh reinforcement of the abdominal wall. METHODS: In a pilot case series, seven patients suffering from complex PSHs (>=5 cm diameter and/or recurrence) underwent surgery and were treated by intraperitoneal onlay technique (IPOM) with a synthetic 3-D funnel-shaped mesh implant. The demographics, perioperative, and follow-up data are presented in this report. RESULTS: The surgical strategy varied between purely laparoscopic (n = 1), laparoscopically assisted (hybrid n = 3), or open techniques (n = 3) using original or suture reconstructed mesh devices. The funnel mesh implantations in IPOM technique were combined with attached flat meshes in the appropriate position of the abdominal wall. No procedure-related complications occurred. The mean length of hospital stay was 12 days and the mean operating time was 171 min. No recurrence of PSH or incisional hernias was observed during a mean follow-up period of 12.3 months (range from 7 to 22). CONCLUSION: The use of a 3-D mesh implant has so far shown to be a promising option in the treatment of primary and recurrent PSHs. Its use proved to be reasonable in both laparoscopic and open IPOM technique. PSHs were preferably repaired using the original, unmodified implant, but when we also found it safe to incise, place and then suture the mesh around the pre-existing ostomy. PMID- 25112387 TI - Look carefully to the heels! A potentially treatable cause of spastic paraplegia. PMID- 25112388 TI - Barth syndrome without tetralinoleoyl cardiolipin deficiency: a possible ameliorated phenotype. AB - Barth syndrome (BTHS) is an X-linked disorder characterised by cardiac and skeletal myopathy, growth delay, neutropenia and 3-methylglutaconic aciduria (3 MGCA). Patients have TAZ gene mutations which affect metabolism of cardiolipin, resulting in low tetralinoleoyl cardiolipin (CL(4)), an increase in its precursor, monolysocardiolipin (MLCL), and an increased MLCL/CL(4) ratio. During development of a diagnostic service for BTHS, leukocyte CL(4) was measured in 156 controls and 34 patients with genetically confirmed BTHS. A sub-group of seven subjects from three unrelated families was identified with leukocyte CL(4) concentrations within the control range. This had led to initial false negative disease detection in two of these patients. MLCL/CL(4) in this subgroup was lower than in other BTHS patients but higher than controls, with no overlap between the groups. TAZ gene mutations in these families are all predicted to be pathological. This report describes the clinical histories of these seven individuals with an atypical phenotype: some features were typical of BTHS (five have had cardiomyopathy, one family has a history of male infant deaths, three have growth delay and five have 3-MGCA) but none has persistent neutropenia, five have excellent exercise tolerance and two adults are asymptomatic. This report also emphasises the importance of measurement of MLCL/CL(4) ratio rather than CL(4) alone in the biochemical diagnosis of the BTHS. PMID- 25112389 TI - Ten years of the international Pompe survey: patient reported outcomes as a reliable tool for studying treated and untreated children and adults with non classic Pompe disease. AB - Pompe disease is a rare, progressive lysosomal storage disorder for which enzyme therapy (ERT) became available in 2006. Four years earlier, the IPA/Erasmus MC survey, an international longitudinal prospective survey, was established to collect information on the natural course of the disease and its burden on patients. The survey is a collaboration between Erasmus MC University Medical Center and the International Pompe Association (IPA) and comprises an annual questionnaire that was specifically designed to assess the symptoms and problems of the disease. Here we review our results of over 10 years of follow-up, and discuss the survey's contribution to the field. Tracking 408 Pompe patients between 2002 and 2013, the cumulative data reveals the broad range of clinical manifestations that interfere with patients' lives. The survey allowed us to quantify the rate of disease progression and the positive effects of ERT on patients' quality of life, fatigue, and participation in daily life. Furthermore, it showed for the first time that survival is reduced in adult Pompe disease and improved by ERT. Our results show that a patient survey can serve as a valuable and reliable tool for obtaining quantifiable information on the natural course of a rare disease and on the effects of therapy in a large cohort over a very long time. Most importantly, by working with patient reported outcomes, the survey provides the data that is truly relevant to the patient and complementary to clinical datasets. PMID- 25112392 TI - In vivo expression of recombinant pregnancy-specific glycoprotein 1a inhibits the symptoms of collagen-induced arthritis. AB - PROBLEM: The contribution of Pregnancy-specific glycoproteins (PSG), the major variant of PSG released into the circulation during pregnancy, to the pregnancy dependent improvement of rheumatoid arthritis (RA) has still not been elucidated. METHOD OF STUDY: Collagen-induced arthritis (CIA) was used to test the hypothesis that PSG1a when released into circulation has a modulatory role on the Th1 pathogenic response, thus improving the CIA symptoms. In vivo expression of PSG1a was induced by injection of the vaccinia (Vac)-based expression vector harboring the complete open-reading frame of PSG1a cDNA. RESULTS: In vivo PSG1a expression during the induction of CIA ameliorated the clinical symptoms, thereby reducing the arthritis score and incidence. Significantly lower levels of IL-17, IL-6, and IFN-gamma, but higher levels of TGF-beta and IL-10 were secreted by collagen type II-stimulated spleen mononuclear cells from Vac-PSG1a-treated mice compared with control mice. Moreover, Vac-PSG1a treatment promoted the increase in splenic CD4+CD25+Foxp3+ Treg cells. CONCLUSION: Pre-clinical Vac-PSG1a treatment suppressed the Th1- and Th17-type-specific responses, leading to an increase in splenic Treg cells as well as IL-10- and TGF-beta-secreting cells, with the CIA symptoms being ameliorated. PMID- 25112393 TI - Super-size me: self biases increase to larger stimuli. AB - Prior work has shown that simple perceptual match responses to pairings of shapes and labels are more efficient if the pairing is associated with the participant (e.g., circle-you) than if it is associated with another familiar person (e.g., square-friend). There is a similar advantage for matching associations with high value rewards (circle-L9) versus low-value rewards (square-L1) (Sui, He, & Humphreys Journal of Experimental Psychology: Human Perception and Performance, 38, 1105-1117, 2012). Here we evaluated the relations between the self- and reward-bias effects by introducing occasional trials in which the size of a shape was varied unexpectedly (large or small vs. a standard medium). Participants favored stimuli that were larger than the standard when stimuli were associated with the self, and this enhancement of self bias was predicted by the degree of self bias that participants showed to standard (medium) sized stimuli. Although we observed a correlation between the magnitudes of the self and reward biases over participants, reward-bias effects were not increased to large stimuli. The data suggest both overlapping and independent components of the self and reward biases, and that self biases are uniquely enhanced when stimuli increase in size, consistent with previously reported motivational biases favoring large stimuli. PMID- 25112391 TI - Adenylosuccinate lyase deficiency. AB - Adenylosuccinate lyase ADSL) deficiency is a defect of purine metabolism affecting purinosome assembly and reducing metabolite fluxes through purine de novo synthesis and purine nucleotide recycling pathways. Biochemically this defect manifests by the presence in the biologic fluids of two dephosphorylated substrates of ADSL enzyme: succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado). More than 80 individuals with ADSL deficiency have been identified, but incidence of the disease remains unknown. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The fatal neonatal form has onset from birth and presents with fatal neonatal encephalopathy with a lack of spontaneous movement, respiratory failure, and intractable seizures resulting in early death within the first weeks of life. Patients with type I (severe form) present with a purely neurologic clinical picture characterized by severe psychomotor retardation, microcephaly, early onset of seizures, and autistic features. A more slowly progressing form has also been described (type II, moderate or mild form), as having later onset, usually within the first years of life, slight to moderate psychomotor retardation and transient contact disturbances. Diagnosis is facilitated by demonstration of SAICAr and S-Ado in extracellular fluids such as plasma, cerebrospinal fluid and/or followed by genomic and/or cDNA sequencing and characterization of mutant proteins. Over 50 ADSL mutations have been identified and their effects on protein biogenesis, structural stability and activity as well as on purinosome assembly were characterized. To date there is no specific and effective therapy for ADSL deficiency. PMID- 25112394 TI - Spatial resolution in visual memory. AB - Representations in visual short-term memory are considered to contain relatively elaborated information on object structure. Conversely, representations in earlier stages of the visual hierarchy are thought to be dominated by a sensory based, feed-forward buildup of information. In four experiments, we compared the spatial resolution of different object properties between two points in time along the processing hierarchy in visual short-term memory. Subjects were asked either to estimate the distance between objects or to estimate the size of one of the objects' features under two experimental conditions, of either a short or a long delay period between the presentation of the target stimulus and the probe. When different objects were referred to, similar spatial resolution was found for the two delay periods, suggesting that initial processing stages are sensitive to object-based properties. Conversely, superior resolution was found for the short, as compared with the long, delay when features were referred to. These findings suggest that initial representations in visual memory are hybrid in that they allow fine-grained resolution for object features alongside normal visual sensitivity to the segregation between objects. The findings are also discussed in reference to the distinction made in earlier studies between visual short-term memory and iconic memory. PMID- 25112395 TI - Time-based event expectations employ relative, not absolute, representations of time. AB - When the timing of an event is predictable, humans automatically form implicit time-based event expectations. We investigated whether these expectations rely on absolute (e.g., 800 ms) or relative (e.g., a shorter duration) representations of time. In a choice-response task with two different pre-target intervals, participants implicitly learned that targets were predictable by interval durations. In a test phase, the two intervals were either considerably shortened or lengthened. In both cases, behavioral tendencies transferred from practice to test according to relative, not absolute, interval duration. We conclude that humans employ relative representations of time periods when forming time-based event expectations. These results suggest that learned time-based event expectations (e.g., in communication and human-machine interaction) should transfer to faster or slower environments if the relative temporal distribution of events is preserved. PMID- 25112396 TI - Interim FDG PET scans in lymphoma: SUV measurement error may impair qPET methodology. PMID- 25112397 TI - Sources of variability in FDG PET imaging and the qPET value: reply to Laffon and Marthan. PMID- 25112398 TI - Targeting post-infarct inflammation by PET imaging: comparison of (68)Ga-citrate and (68)Ga-DOTATATE with (18)F-FDG in a mouse model. AB - Imaging of inflammation early after myocardial infarction (MI) is a promising approach to the guidance of novel molecular interventions that support endogenous healing processes. (18)F-FDG PET has been used, but may be complicated by physiological myocyte uptake. We evaluated the potential of two alternative imaging targets: lactoferrin binding by (68)Ga-citrate and somatostatin receptor binding by (68)Ga-DOTATATE. METHODS: C57Bl/6 mice underwent permanent coronary artery ligation. Serial PET imaging was performed 3 - 7 days after MI using (68)Ga-citrate, (68)Ga-DOTATATE, or (18)F-FDG with ketamine/xylazine suppression of myocyte glucose uptake. Myocardial perfusion was evaluated by (13)N-ammonia PET and cardiac geometry by contrast-enhanced ECG-gated CT. RESULTS: Mice exhibited a perfusion defect of 30 - 40% (of the total left ventricle) with apical anterolateral wall akinesia and thinning on day 7 after MI. (18)F-FDG with ketamine/xylazine suppression demonstrated distinct uptake in the infarct region, as well as in the border zone and remote myocardium. The myocardial standardized uptake value in MI mice was significantly higher than in healthy mice under ketamine/xylazine anaesthesia (1.9 +/- 0.4 vs. 1.0 +/- 0.1). (68)Ga images exhibited high blood pool activity with no specific myocardial uptake up to 90 min after injection (tissue-to-blood contrast 0.9). (68)Ga-DOTATATE was rapidly cleared from the blood, but myocardial SUV was very low (0.10 +/- 0.03). CONCLUSION: Neither (68)Ga nor (68)Ga-DOTATATE is a useful alternative to (18)F FDG for PET imaging of myocardial inflammation after MI in mice. Among the three tested approaches, (18)F-FDG with ketamine/xylazine suppression of cardiomyocyte uptake remains the most practical imaging marker of post-infarct inflammation. PMID- 25112400 TI - [Dementia in families with a Turkish migration background. Organization and characteristics of domestic care arrangements]. AB - BACKROUND: Until recently public health and health services research has not been concerned with people suffering from dementia with a Turkish migration background as a priority. There is little evidence about the situation of this population; however, it is known that these individuals almost always live with their families and are cared for by their families generally without seeking professional support. The aim of this study was to gain insight into the organization and characteristics of home-based care arrangements for people suffering from dementia with a Turkish migration background from the family carer's perspective. METHODS: Interviews with seven family carers. The principles of the grounded theory served as a framework for data analysis. RESULTS: Unconditional commitment to caring for a family member with dementia was identified as the main characteristic of care arrangements in families with a Turkish migration background. Dementia is not a factor that has an impact on the decision of families to assume care responsibility for an affected family member and there is a lack of knowledge about dementia in general. There are various inhibiting factors for the utilization of formal services and the family carers in this sample complained that the available services are not culturally sensitive. CONCLUSION: There seems to be an extensive need for information and counselling regarding care dependency and dementia among the Turkish community. To provide personal-centred care and relief to these families in the future, efforts should be made to adapt the current care system to the specific needs and demands of this population. Cultural sensitivity in general and individual subjective needs of persons with a Turkish migration background affected by dementia should be taken into account. PMID- 25112399 TI - Diagnostic accuracy of whole-body PET/MRI and whole-body PET/CT for TNM staging in oncology. AB - PURPOSE: In various tumours PET/CT with [(18)F]FDG is widely accepted as the diagnostic standard of care. The purpose of this study was to compare a dedicated [(18)F]FDG PET/MRI protocol with [(18)F]FDG PET/CT for TNM staging in a cohort of oncological patients. METHODS: A dedicated [(18)F]FDG PET/MRI protocol was performed in 73 consecutive patients (mean age of 59 years, range 21 - 85 years) with different histologically confirmed solid primary malignant tumours after a routine clinical FDG PET/CT scan (60 min after injection of 295 +/- 45 MBq [(18)F]FDG). TNM staging according to the 7th edition of the AJCC Cancer Staging Manual was performed by two readers in separate sessions for PET/CT and PET/MRI images. Assessment of the primary tumour and nodal and distant metastases with FDG PET/CT and FDG PET/MRI was based on qualitative and quantitative analyses. Histopathology, and radiological and clinical follow-up served as the standards of reference. A McNemar test was performed to evaluate the differences in diagnostic performance between the imaging procedures. RESULTS: From FDG PET/CT and FDG PET/MRI T stage was correctly determined in 22 (82 %) and 20 (74 %) of 27 patients, N stage in 55 (82 %) and 56 (84 %) of 67 patients, and M stage in 32 (76 %) and 35 (83 %) of 42 patients, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for lymph node metastases were 65 %, 94 %, 79 %, 89 % and 87 % for PET/CT, and 63 %, 94 %, 80 %, 87 % and 85 % for PET/MRI. The respective values for the detection of distant metastases were 50 %, 82 %, 40 %, 88 % and 76 % for PET/CT, and 50 %, 91 %, 57 %, 89 % and 83 % for PET/MRI. Differences between the two imaging modalities were not statistically significant (P > 0.05). CONCLUSION: According to our results, FDG PET/CT and FDG PET/MRI are of equal diagnostic accuracy for TNM staging in patients with solid tumours. PMID- 25112401 TI - ["So I would have been sitting at home and moping...": How do older single people in need of support experience companionship by volunteers after discharge from hospital?]. AB - BACKGROUND: Despite the well-known link between social support and health as well as quality of life only a few scientifically meaningful studies have been carried out to actively promote social support. In the +P Project (post-hospital lay support for patients) elderly people in need of support after a stay in hospital are accompanied in their daily life by volunteers. The qualitative research part in the study evaluates conditions which led to the adoption of the support by the volunteers and how the elderly people experienced this companionship. METHODS: The analysis followed the grounded theory method. In a theoretical sampling nine accompanied people were identified and participated in narrative interviews regarding their experience of the voluntary support. RESULTS: In addition to personality traits of the elderly and perceived seriousness of the project the interpersonal relationship was important for the adoption of the companionship. Key factors were the perceived similarity between the older people and their supporters as well as confidence in the volunteers and their skills. The support contributed to facilitating and enriching the daily life of the elderly and even friendships with the volunteers developed. CONCLUSIONS: The results indicate that volunteers can help to compensate a lack of social support for the elderly. The results confirm theoretical models of coping with age and disease-related losses and models of social relations in old age. At the same time this study underpins political recommendations to strengthen community engagement to promote social networks for older people. PMID- 25112402 TI - Multimodal sensor-based fall detection within the domestic environment of elderly people. AB - BACKGROUND: Falls represent a major threat to the health of the elderly and are a growing burden on the healthcare systems. With the growth of the elderly population within most societies efficient fall detection becomes increasingly important; however, existing fall detection systems still fail to produce reliable results. OBJECTIVES: A study was carried out on sensor-based fall detection, analysis of falls with the help of fall protocols and the analysis of user acceptance of fall detection sensor technology through questionnaires. MATERIAL AND METHODS: A total of 28 senior citizens were recruited from a German community-dwelling population. The primary goal was a sensor-based detection of falls with accelerometers, video cameras and microphones. Details of the falls were analyzed with the help of medical geriatric assessments and standardized fall protocols. The study duration was 8 weeks and required a maximum of nine visits per subject. RESULTS: The study participants were 28 subjects with a mean age of 74.3 and a standard deviation (SD) of +/- 6.3 years of which 12 were male and 16 female. A total of 1225.7 measurement days were recorded from all participants and the algorithms detected 2.66 falls per day. During the study period 15 falls occurred and 12 of these falls were correctly recognized by the fall detection system. CONCLUSION: Current fall detection technologies work well under laboratory conditions but it is still problematic to produce reliable results when these technologies are applied to real life conditions. Acceptance towards the sensors decreased after study participation although the system was generally perceived as useful or very useful. PMID- 25112403 TI - Lysyl oxidase rs1800449 polymorphism and cancer risk among Asians: evidence from a meta-analysis and a case-control study of colorectal cancer. AB - Growing evidence has indicated that lysyl oxidase (LOX) G473A polymorphism (rs1800449) is associated with cancer risk among Asians. However, results of single center and small sample study lack enough power. We first investigated the effect of LOX G473A polymorphism on cancer risk among Asians by a meta-analysis, and then further validated this association by a case-control study of colorectal cancer (CRC) with LOX G473A polymorphism in a Chinese population. STATA 12.0 software was used for the meta-analysis. The relationships were evaluated by calculating the pooled odds ratios (ORs) and their 95 % confidence intervals (CIs). In a case-control study comprising 577 CRC patients and 696 controls, LOX G473A polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Logistic regression was used to evaluate genetic associations with the occurrence of CRC. The results of our meta analysis, including seven case-control studies with a total of 2,377 cancer patients and 2,499 controls, suggested that LOX G473A polymorphism might be associated with an increased risk of cancer among Asians. In addition, results of a case-control study indicated that individuals with the AA or AG genotype had a significantly increased susceptibility to CRC occurrence, compared with individuals who had GG genotype. Overall, this meta-analysis and case-control study of CRC observed convincing association of LOX G473A polymorphism with cancer risk in Asians; our study would contribute to complete elucidation of carcinogenesis. PMID- 25112406 TI - Malignant transformation of craniopharyngioma with detailed follow-up. AB - A 29-year-old male patient was admitted into hospital with the main complaint of progressive visual disturbance. Both CT SCAN and MRI demonstrated a cystic-solid contrast-enhancing sellar-suprasellar mass with obvious calcification. Histopathological examination of the first resected specimen showed a typical appearance of adamantinomatous craniopharyngioma. The patient received gamma knife therapy after his first operation because of partial tumor removal. He experienced two relapses in the subsequent 2 years, for which only surgical resection was performed. The later histopathology presented malignant appearance with tumor cells moderate to severe pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio, high mitotic activity (30/10 high power fields) and focal coagulative necrosis. The patient died 9 months after identification of histologic malignancy. Clinical and histopathological features, biological behavior of one case of malignant craniopharyngioma were discussed, with a brief review of the relevant literature. PMID- 25112407 TI - Effect of aqueous leaf extract of Dalbergia sissoo Roxb. on spermatogenesis and fertility in male mice. AB - OBJECTIVES: Antifertility effects of Dalbergia sissoo in male mice were investigated. METHODS: Adult Parkes strain male mice were orally administered aqueous leaf extract of Dalbergia sissoo (50 and 100 mg/kg body weight/day) or distilled water or no treatment (controls) for 35 days (n = 5/group). Motility, viability and number of spermatozoa in the cauda epididymidis; testis histology; serum level of testosterone; and toxicological parameters were evaluated. To assess reversibility, more mice were treated with 100 mg/kg body weight of Dalbergia sissoo or distilled water (n = 5/group) for 35 days and sacrificed 56 days later. Fertility was also assessed separately. RESULTS: Histologically, testes of Dalbergia-treated mice showed dissimilar degenerative changes in the seminiferous tubules. Significant reductions were noted (i) in epididymal sperm motility, viability and number, and (ii) in serum level of testosterone in Dalbergia-treated mice compared to controls. However, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine, and haematological parameters were not affected. Also libido of Dalbergia-treated males showed no change, but their fertility was markedly suppressed. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels. CONCLUSIONS: Dalbergia sissoo treatment caused reversible suppression of spermatogenesis and fertility in P mice, without eliciting detectable toxic effects. PMID- 25112405 TI - Mucosal vaccine delivery by non-recombinant spores of Bacillus subtilis. AB - Development of mucosal vaccines strongly relies on an efficient delivery system and, over the years, a variety of approaches based on phages, bacteria or synthetic nanoparticles have been proposed to display and deliver antigens. The spore of Bacillus subtilis displaying heterologous antigens has also been considered as a mucosal vaccine vehicle, and shown able to conjugate some advantages of live microrganisms with some of synthetic nanoparticles. Here we review the use of non-recombinant spores of B. subtilis as a delivery system for mucosal immunizations. The non-recombinant display is based on the adsorption of heterologous molecules on the spore surface without the need of genetic manipulations, thus avoiding all concerns about the use and environmental release of genetically modified microorganisms. In addition, adsorbed molecules are stabilized and protected by the interaction with the spore, suggesting that this system could reduce the rapid degradation of the antigen, often observed with other delivery systems and identified as a major drawback of mucosal vaccines. PMID- 25112408 TI - Prognostic role of CD44 expression in osteosarcoma: evidence from six studies. AB - BACKGROUND: Numerous studies examining the relationship between CD44 expression and prognostic impact in patients with osteosarcoma have yielded inconclusive results. The aim of this meta-analysis was carried out to investigate the relationship between CD44 expression and the survival in patients with osteosarcoma. METHODS: We therefore conducted a meta-analysis to provide a comprehensive evaluation of the prognostic role of CD44 expression on the overall survival rate and metastasis, which compared the positive and negative expression of CD44 in patients of the available studies. RESULTS: A detailed search was made in MEDLINE and EMBASE for relevant original articles published in English. Finally, a total of six studies with 329 osteosarcoma patients were involved to estimate the relationship between CD44 expression and metastasis of tumor and overall survival. Positive expressions of CD44 did not predict neoplasm metastasis (RR = 1.36, 95% CI: 1.00-1.84, P = 0.50), and the results indicated that higher expression of CD44 could not predict poorer survival in osteosarcoma with the pooled HR of 0.55 (95% CI: 0.27-1.13, P = 0.47). CONCLUSIONS: The findings from this present meta-analysis suggest that CD44 expression is not associated with overall survival rate and metastasis in osteosarcoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1373995521295618. PMID- 25112409 TI - Gaps in preparedness of clergy and healthcare providers to address mental health needs of returning service members. AB - To elucidate gaps in the preparedness of clergy and healthcare providers to care for service members (SM) with deployment-related mental health needs. Participants identified clinically relevant symptoms in a standardized video role play of a veteran with deployment-related mental health needs and discussed their preparedness to deal with SM. Clergy members identified suicide and depression most often, while providers identified difficulty sleeping, low energy, nightmares and irritability. Neither clergy nor providers felt prepared to minister to or treat SM with traumatic brain injury. Through a mixed methods approach, we identified gaps in preparedness of clergy and healthcare providers in dealing with the mental health needs of SM. PMID- 25112411 TI - Low drain fluid amylase predicts absence of pancreatic fistula following pancreatectomy. AB - INTRODUCTION: Improvements in the ability to predict pancreatic fistula could enhance patient outcomes. Previous studies demonstrate that drain fluid amylase on postoperative day 1 (DFA1) is predictive of pancreatic fistula. We sought to assess the accuracy of DFA1 and to identify a reliable DFA1 threshold under which pancreatic fistula is ruled out. METHODS: Patients undergoing pancreatic resection from November 1, 2011 to December 31, 2012 were selected from the American College of Surgeons-National Surgical Quality Improvement Program Pancreatectomy Demonstration Project database. Pancreatic fistula was defined as drainage of amylase-rich fluid with drain continuation >7 days, percutaneous drainage, or reoperation for a pancreatic fluid collection. Univariate and multi variable regression models were utilized to identify factors predictive of pancreatic fistula. RESULTS: DFA1 was recorded in 536 of 2,805 patients who underwent pancreatic resection, including pancreaticoduodenectomy (n = 380), distal pancreatectomy (n = 140), and enucleation (n = 16). Pancreatic fistula occurred in 92/536 (17.2%) patients. DFA1, increased body mass index, small pancreatic duct size, and soft texture were associated with fistula (p < 0.05). A DFA1 cutoff value of <90 U/L demonstrated the highest negative predictive value of 98.2%. Receiver operating characteristic (ROC) curve confirmed the predictive relationship of DFA1 and pancreatic fistula. CONCLUSION: Low DFA1 predicts the absence of a pancreatic fistula. In patients with DFA1 < 90 U/L, early drain removal is advisable. PMID- 25112412 TI - Reliability and validity of the Finnish version of the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, patient self-report section. AB - BACKGROUND: The American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) is one of the most widely used shoulder outcome tools in clinical work and in scientific studies. However, it has not been validated in the Finnish language. The aims of this study were to cross-culturally adapt the ASES to the Finnish language and to study the psychometric properties of the self report section of the ASES. METHODS: A total of 105 patients with shoulder symptoms answered the questionnaires of the ASES, a single disability question, the Simple Shoulder Test (SST), and the Short-Form 36 Health Survey (SF-36). The reliability of the ASES questionnaire was studied using a test-retest procedure at 2-week intervals. Psychometric assessment was performed by testing the construct validity, internal consistency, the criterion validity, and the convergent validity of the ASES. RESULTS: The reproducibility and internal consistency of the ASES were 0.83 (95% CI 0.70 to 0.90) and 0.88 (95% Cl 0.84 to 0.91). There were no significant differences between the diagnostic groups in the pain scores from the ASES, and the function score was significantly higher in the instability group compared to the other groups. The convergent validity of the ASES correlated with the SST, r = 0.73 (p < 0.001); the single disability question, r = -0.74 (p < 0.001); and the Physical Component Score of the SF-36, r = 0.57 (p < 0.001). CONCLUSIONS: The Finnish version of the ASES proved to be a reliable and valid tool for assessing shoulder disabilities in patients with different shoulder diagnoses, including rotator cuff disease, instability, and osteoarthritis. PMID- 25112410 TI - Lithium chloride therapy fails to improve motor function in a transgenic mouse model of Machado-Joseph disease. AB - The accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed as a promising therapeutic agent for several neurodegenerative diseases. We tested the efficacy of chronic lithium (10.4 mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an inherited neurodegenerative disease, caused by an expansion of a polyglutamine tract within the protein ataxin-3. A battery of behavioral tests was used to assess disease progression. In spite of activating autophagy, as suggested by the increased levels of Beclin-1, Atg7, and LC3-II, and a reduction in the p62 protein levels, lithium administration showed no overall beneficial effects in this model concerning motor performance, showing a positive impact only in the reduction of tremors at 24 weeks of age. Our results do not support lithium chronic treatment as a promising strategy for the treatment of Machado-Joseph disease (MJD). PMID- 25112414 TI - Developmental prosopagnosia referred to outpatient psychiatric service. PMID- 25112413 TI - Renal function assessment in child and adolescent heart transplant recipients during routine cardiac catheterization. AB - CKD identification after pediatric heart transplantation (PHT) is limited by inaccuracies in estimates of GFR. We hypothesized that GFR can be measured by a modified iohexol clearance protocol in PHT recipients and that the CKiD formula provides a better estimate of GFR than other estimating equations. A cross sectional study of PHT recipients, ages 2-18 yr, undergoing coronary angiography was undertaken. The angiography dose of iohexol was divided by the area under the curve from three iohexol levels post-infusion to calculate GFR. Agreement between iGFR and multiple estimating equations (eGFR) was assessed. In 31 subjects, median age was 15.0 yr (IQR 7.6, 16.6). Mean iGFR was 93.8 (s.d. 22.5) mL/min/1.73 m(2) ; 16 (52%) had an iGFR <90 mL/min/1.73 m(2) . The full CKiD formula (mean eGFR 88.9, s.d. 14.9) had low bias (-5.0), narrowest 95% limits of agreement (-42.0, 32.1), highest 30% (94%) and 10% (52%) accuracy, and highest correlation coefficient (0.576) relative to iGFR. We describe a novel modified iohexol clearance method to assess GFR after PHT. Over half of the cohort had an iGFR <90, suggesting CKD. The full CKiD formula performs best with respect to bias, accuracy, and correlation. PMID- 25112415 TI - Low levels of 25-hydroxy vitamin D and active 1,25-dihydroxyvitamin D independently associated with type 2 diabetes mellitus in older Australian men: the Concord Health and Ageing in Men Project. AB - OBJECTIVES: To examine the associations between serum 25-hydroxyvitamin D (25OHD) levels and the active vitamin D metabolite, 1,25-hydroxyvitamin D (1,25OHD), with type 2 diabetes mellitus (DM) in community-living men aged 70 and older. DESIGN: Cross-sectional. SETTING: A population-based, cross-sectional analysis of the baseline phase of the Concord Health and Ageing in Men Project (CHAMP), a large epidemiological study conducted in Sydney between January 2005 and May 2007. PARTICIPANTS: Community dwelling men aged 70 and older taking part in CHAMP (N = 1,659). MEASUREMENTS: Serum 25OHD and 1,25OHD levels, presence of DM, age, country of birth, season of blood collection, sun exposure, body mass index, vitamin D supplement use, statin use, income, measures of health, depression, activity of daily living disabilities, parathyroid hormone, estimated glomerular filtration rate, phosphate, and calcium. RESULTS: The prevalence of DM was 20.0%. There was a significant association between low 25OHD and 1,25OHD levels and DM that remained after adjustment for a wide range of confounders and covariates of clinical significance such as comorbidity, renal function, calciotropic hormones, and medications. CONCLUSION: 25OHD and 1,25OHD levels were associated with DM. The independent association between serum 25OHD and 1,25OHD concentrations and DM raises the question of whether each of the two vitamin D metabolites may influence DM through different biological mechanisms and pathways. PMID- 25112416 TI - A drastic substituent effect on the emission properties of quinone diimine models and valuable insight into the excited states of emeraldine. AB - The (alpha-NR,alpha'-NR,N,N'-(C6H4C=CSiMe3)4)[Q] models ([Q] = -N=C6H4=N-) exhibit upper excited state emissions Sn,Tn -> S0 (n >1, R = Boc), similar to emeraldine, vs. a fluorescence S1 -> S0 (R = H), driven by a large change in dihedral angles made by the NR-C6H4 and [Q] planes and intramolecular H-bonds. PMID- 25112417 TI - Hepatitis mouse models: from acute-to-chronic autoimmune hepatitis. AB - Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, raised plasma liver enzymes, the presence of autoantibodies and regulatory T-cell (Tregs) dysfunction. The clinical course is heterogeneous, manifested by a fulminant or indolent course. Although genetic predisposition is well accepted, the combination with currently undefined environmental factors is crucial for the development of the disease. Progress in the development of reliable animal models provides added understanding of the pathophysiology of AIH, and these will be very useful in evaluating potential therapeutics. It appears that artificially breaking tolerance in the liver is easy. However, maintaining this state of tolerance breakdown, to get chronic hepatitis, is difficult because liver immune homeostasis is strongly regulated by several immune response inhibitory mechanisms. For example, Tregs are crucial regulators in acute and chronic hepatitis, and C57BL/6 mice are most prone to experimental AIH. Immunization of C57BL/6 mice with liver (AIH) autoantigens (CYP2D6/FTCD or IL-4R) and the disturbance of liver regulatory mechanism(s), leading to experimental AIH, are likely to be most representative of human AIH pathology. PMID- 25112420 TI - Cardiopulmonary and anesthetic effects of the combination of butorphanol, midazolam and alfaxalone in Beagle dogs. AB - OBJECTIVE: To evaluate the physiological variables, arterial blood gas values, induction of anesthesia quality, and recovery quality using the combination of butorphanol, midazolam and alfaxalone in dogs. ANIMALS: Ten healthy adult Beagle dogs weighing 8.3 +/- 3.1 kg. METHODS: Rectal temperature (T), pulse rate (PR), respiratory rate (f(R)), mean arterial pressure (MAP), and arterial blood gases were measured and recorded prior to intravenous (IV) administration of butorphanol, prior to administration of both midazolam and alfaxalone IV 10 minutes later, then every 5 minutes for 20 minutes. M-mode echocardiographic left ventricular (LV) indices were measured before and 5 minutes after administration of alfaxalone. Qualitative scores for induction of anesthesia and recovery were allocated, duration of anesthesia and recovery were calculated, and adverse events were recorded. RESULTS: Scores for induction and recovery quality were excellent. No significant adverse events were observed. Mean +/- SD time from induction to extubation and to standing (full recovery) was 29 +/- 6 and 36 +/- 8 minutes, respectively. There were statistically significant changes in PR, f(R) and MAP after drug administration. Transient hypercarbia developed after alfaxalone injection. The echocardiographic LV indices were reduced after alfaxalone injection, although those changes were not statistically significant. CONCLUSIONS AND CLINICAL RELEVANCE: The combination of butorphanol, midazolam and alfaxalone provided excellent quality of induction of anesthesia and exerted minimal cardiopulmonary effects in healthy dogs. PMID- 25112419 TI - Structural and morphometric comparison of the molar teeth in pre-eruptive developmental stage of PACAP-deficient and wild-type mice. AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide with widespread distribution. It plays pivotal role in neuronal development. PACAP-immunoreactive fibers have been found in the tooth pulp, and recently, it has been shown that PACAP may also play a role in the regeneration of the periodontium after luxation injuries. However, there is no data about the effect of endogenous PACAP on tooth development. Ectodermal organogenesis including tooth development is regulated by different members of bone morphogenetic protein (BMP), fibroblast growth factor (FGF), hedgehog (HH), and Wnt families. There is also a growing evidence to support the hypothesis that PACAP interacts with sonic hedgehog (SHH) receptor (PTCH1) and its downstream target (Gli1) suggesting its role in tooth development. Therefore, our aim was to study molar tooth development in mice lacking endogenous PACAP. In this study morphometric, immunohistochemical and structural comparison of molar teeth in pre eruptive developmental stage was performed on histological sections of 7-day-old wild-type and PACAP-deficient mice. Further structural analysis was carried out with Raman microscope. The morphometric comparison of the 7-day-old samples revealed that the dentin was significantly thinner in the molars of PACAP deficient mice compared to wild-type animals. Raman spectra of the enamel in wild type mice demonstrated higher diversity in secondary structure of enamel proteins. In the dentin of PACAP-deficient mice higher intracrystalline disordering in the hydroxyapatite molecular structure was found. We also obtained altered SHH, PTCH1 and Gli1 expression level in secretory ameloblasts of PACAP deficient mice compared to wild-type littermates suggesting that PACAP might play an important role in molar tooth development and matrix mineralization involving influence on SHH signaling cascade. PMID- 25112421 TI - Development of an ELISA microarray assay for the sensitive and simultaneous detection of ten biodefense toxins. AB - Plant and microbial toxins are considered bioterrorism threat agents because of their extreme toxicity and/or ease of availability. Additionally, some of these toxins are increasingly responsible for accidental food poisonings. The current study utilized an ELISA-based protein antibody microarray for the multiplexed detection of ten biothreat toxins, botulinum neurotoxins (BoNT) A, B, C, D, E, F, ricin, shiga toxins 1 and 2 (Stx), and staphylococcus enterotoxin B (SEB), in buffer and complex biological matrices. The multiplexed assay displayed a sensitivity of 1.3 pg mL(-1) (BoNT/A, BoNT/B, SEB, Stx-1 and Stx-2), 3.3 pg mL( 1) (BoNT/C, BoNT/E, BoNT/F) and 8.2 pg mL(-1) (BoNT/D, ricin). All assays demonstrated high accuracy (75-120 percent recovery) and reproducibility (most coefficients of variation <20%). Quantification curves for the ten toxins were also evaluated in clinical samples (serum, plasma, nasal fluid, saliva, stool, and urine) and environmental samples (apple juice, milk and baby food) with overall minimal matrix effects. The multiplex assays were highly specific, with little cross-reactivity observed between the selected toxin antibodies. The results demonstrate a multiplex microarray that improves current immunoassay sensitivity for biological warfare agents in buffer, clinical, and environmental samples. PMID- 25112418 TI - Pituitary adenylate cyclase-activating polypeptide (PACAP) signalling enhances osteogenesis in UMR-106 cell line. AB - Presence of the pituitary adenylate cyclase-activating polypeptide (PACAP) signalling has been proved in various peripheral tissues. PACAP can activate protein kinase A (PKA) signalling via binding to pituitary adenylate cyclase activating polypeptide type I receptor (PAC1), vasoactive intestinal polypeptide receptor (VPAC) 1 or VPAC2 receptor. Since little is known about the role of this regulatory mechanism in bone formation, we aimed to investigate the effect of PACAP on osteogenesis of UMR-106 cells. PACAP 1-38 as an agonist and PACAP 6-38 as an antagonist of PAC1 were added to the culture medium. Surprisingly, both substances enhanced protein expressions of collagen type I, osterix and alkaline phosphatase, along with higher cell proliferation rate and an augmented mineralisation. Although expression of PKA was elevated, no alterations were detected in the expression, phosphorylation and nuclear presence of CREB, but increased nuclear appearance of Runx2, the key transcription factor of osteoblast differentiation, was shown. Both PACAPs increased the expressions of bone morphogenetic proteins (BMPs) 2, 4, 6, 7 and Smad1 proteins, as well as that of Sonic hedgehog, PATCH1 and Gli1. Data of our experiments indicate that activation of PACAP pathway enhances bone formation of UMR-106 cells and PKA, BMP and Hedgehog signalling pathways became activated. We also found that PACAP 6-38 did not act as an antagonist of PACAP signalling in UMR-106 cells. PMID- 25112423 TI - Speech-language pathology practices with Indigenous Australians with acquired communication disorders. AB - PURPOSE: Little is known about the needs of Indigenous Australian adults with acquired communication disorders (ACD) following stroke or brain injury and how these needs are met by speech-language pathology (SLP) services. In order for the profession to respond to the challenges of providing culturally appropriate, well tailored and accessible services, more information on current practice and SLPs' concerns and attitudes is required. METHOD: This paper reports on a national survey with completed responses from 112 SLPs, who worked with adult neurological populations, about their levels of contact with Indigenous clients, cultural competency training and potential sources of support. RESULT. Of the total respondents, 63 SLPs reported clinical contact with Indigenous clients and :they also answered questions on their assessment, intervention and discharge practices; liaison with family; and involvement with Aboriginal Health Professionals and interpreters. This group reported insufficient knowledge about Indigenous culture, lack of support and lower levels of confidence overall in working with these clients as compared to non-Indigenous clients. They wanted more flexible services for their Indigenous clients, good access to interpreters and culturally appropriate assessments and treatments delivered in culturally appropriate settings. CONCLUSION: This research provides a useful starting point towards understanding SLPs' perspectives and practice at a national level. PMID- 25112425 TI - A new titanosauriform sauropod (Dinosauria: Saurischia) from the Lower Cretaceous of Hyogo, Japan. AB - A new genus and species of titanosauriform sauropod is erected based on a partial skeleton found in the Lower Cretaceous Sasayama Group of Hyogo Prefecture, SW Japan. The new taxon is here named as Tambatitanis amicitiae gen. et sp. nov., which is diagnosed by the following features of the caudal vertebrae, chevrons and braincase: the postzygapophysis and the summit of the neural spine of the anterior caudal vertebrae are located beyond the posterior border of the centrum, the spine of the anterior caudal vertebrae is curved strongly anteriorly and bow shaped in lateral view, the summit of the neural spine is expanded and hemispherical with its anterior face excavated by the posterodorsal extension of a deep and narrow SPRF, the transverse process of the anterior caudal vertebrae are short and L shaped, the anterior chevron is the longest among sauropods in proportion to body size, the distal ends of the anterior chevrons are rod-shaped, the distal ends of the mid chevrons are transversely thin and anteroposteriorly long without cranial processes, and the dorsal border of the shaft of the paroccipital process that forms the ventral margin of the posttemporal fenestra is short mediolaterally and V-shaped in posterior view. A phylogenetic analysis suggests that T. amicitiae is a basal titanosauriform, possibly belonging to the East Asian endemic clade Euhelopodidae. The caudals and chevrons are described in detail in order to document highly autapomorphic features of the new taxon as well as potentially phylogenetically informative characters. The discovery of T. amicitiae suggests that East Asian basal titanosauriforms were diverse not only in the number of the taxa but also in the morphological variation of the caudal elements. PMID- 25112426 TI - Systematics, morphology, and ecological history of the Mascarene starlings (Aves: Sturnidae) with the description of a new genus and species from Mauritius. AB - Two endemic starlings, both extinct, have been described from the Mascarene Islands of Reunion and Rodrigues: the Hoopoe Starling, Huppe or Reunion Crested Starling Fregilupus varius, which is known from 19 skins and a single Holocene proximal end of a fossil femur, and the Rodrigues Starling Necropsar rodericanus, which is known as specimens only from fossils of most skeletal elements. Both were recorded alive in early accounts of Mascarene faunas. A third species of starling Cryptopsar ischyrhynchus gen. nov. sp. nov. is described herein from fossils from Mauritius, but was never reported in the early literature. This paper provides an analysis of the Sturnidae of the Mascarene Islands based on newly discovered fossil remains, and details historical reports and accounts. Their ecology and extinction are interpreted from historical evidence. Necropsar, Cryptopsar and Fregilupus clearly form part of the same clade, but morphological analysis shows that Necropsar and Cryptopsar are more closely related to each other than to Fregilupus and may have been part of a different colonisation event. All three genera appear to have their origins in SE Asia and have morphological similarities with the SE Asian sturnid genera, Sturnia and Gracupica, so they presumably colonised the islands via island-hopping during lower sea level stands. PMID- 25112424 TI - Molecular characterization of the thioredoxin system from Methanosarcina acetivorans. AB - The thioredoxin system, composed of thioredoxin reductase (TrxR) and thioredoxin (Trx), is widely distributed in nature, where it serves key roles in electron transfer and in the defense against oxidative stress. Although recent evidence reveals Trx homologues are almost universally present among the methane-producing archaea (methanogens), a complete thioredoxin system has not been characterized from any methanogen. We examined the phylogeny of Trx homologues among methanogens and characterized the thioredoxin system from Methanosarcina acetivorans. Phylogenetic analysis of Trx homologues from methanogens revealed eight clades, with one clade containing Trxs broadly distributed among methanogens. The Methanococci and Methanobacteria each contain one additional Trx from another clade, respectively, whereas the Methanomicrobia contain an additional five distinct Trxs. Methanosarcina acetivorans, a member of the Methanomicrobia, contains a single TrxR (MaTrxR) and seven Trx homologues (MaTrx1 7), with representatives from five of the methanogen Trx clades. Purified recombinant MaTrxR had 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) reductase and oxidase activities. The apparent Km value for NADPH was 115-fold lower than that for NADH, consistent with NADPH as the physiological electron donor to MaTrxR. Purified recombinant MaTrx2, MaTrx6 and MaTrx7 exhibited dithiothreitol- and lipoamide-dependent insulin disulfide reductase activities. However, only MaTrx7, which is encoded adjacent to MaTrxR, could serve as a redox partner to MaTrxR. These results reveal that M. acetivorans harbors at least three functional and distinct Trxs, and a complete thioredoxin system composed of NADPH, MaTrxR and at least MaTrx7. This is the first characterization of a complete thioredoxin system from a methanogen, which provides a foundation to understand the system in methanogens. PMID- 25112427 TI - Revision of the Oriental genus Horniella Raffray (Coleoptera, Staphylinidae, Pselaphinae). AB - The Oriental pselaphine genus Horniella Raffray, 1905 (tribe Tyrini: subtribe Somatipionina) is redefined and revised. Twenty-five new species are described: H. centralis Yin & Li, sp. n., H. confragosa Yin & Li, sp. n., H. dao Yin & Li, sp. n., H. hongkongensis Yin & Li, sp. n., H. nakhi Yin & Li, sp. n., H. schuelkei Yin & Li, sp. n., H. sichuanica Yin & Li, sp. n., H. simplaria Yin & Li, sp. n., and H. tianmuensis Yin & Li, sp. n. from China, H. himalayica Yin & Li, sp. n. from Nepal and North India, H. asymmetrica Yin & Li, sp. n., H. burckhardti Yin & Li, sp. n., H. intricata Yin & Li, sp. n., H. kaengkrachan Yin & Li, sp. n., H. khaosabap Yin & Li, sp. n., H. loebli Yin & Li, sp. n., H. phuphaman Yin & Li, sp. n., H. prolixo Yin & Li, sp. n., and H. schwendingeri Yin & Li, sp. n. from Thailand, H. philippina Yin & Li, sp. n. from the Philippines, H. awana Yin & Li, sp. n., H. gigas Yin & Li, sp. n., H. pilosa Yin & Li, sp. n., and H. smetanai Yin & Li, sp. n. from Malaysia, and H. cibodas Yin & Li, sp. n. from Indonesia. The two previously described species, H. hirtella Raffray, 1901 (type species) from Sri Lanka and H. falcis Yin & Li, 2010 from China are redescribed, and a lectotype is designated for H. hirtella. Illustrations of habitus and important diagnostic features, an identification key, and distributional maps for all species are provided. Eleven unidentified species represented only by females are left unnamed. Illustrations of the habitus and the genital complex, and label data of these species are given to facilitate future study. All available data indicates that species of Horniella typically inhabit leaf litter of various kinds of forests, and can be most efficiently collected by sifting and use of Winkler-Moczarski extractors. PMID- 25112428 TI - A review of Northern Peruvian glassfrogs (Centrolenidae), with the description of four new remarkable species. AB - Peru is well known for amphibian diversity and endemism, yet there have been relatively few field studies of glassfrog (Centrolenidae) diversity in this country. Research in Colombia and Ecuador indicates that centrolenid diversity is higher in the northern Andes. However, part of this trend appears to be due to sampling effort. We conducted fieldwork throughout northern Peru, and based on phylogenetic analysis of DNA sequences, combined with bioacoustic and morphological analyses of new and available material we now recognize 33 species from the country (versus 30 species prior to this work). Field surveys led to the discovery of four remarkable species: Centrolene charapita new species is a large, ornamented glassfrog that appears to be sister to Ce. geckoideum; Chimerella corleone new species represents the second-known member of the genus Chimerella; Cochranella guayasamini new species is the second-known member of the genus with humeral spines; and Hyalinobatrachium anachoretus new species occurs in the cloud forest of the east-Andean versant in Peru. In addition to the new species described here, we provide new country records, new localities including range extensions of up to 875 km, information on diagnostic characters and phylogenetic relationships, call and larval descriptions, and observations on natural history for several Peruvian centrolenids. Our results also revealed several taxonomic problems concerning species of the genus Rulyrana, and we conclude that R. croceopodes and R. tangarana are junior synonyms of R. saxiscandens. By implication of our phylogenetic analyses, we recognize the following new combinations: Espadarana audax new combination, Espadarana durrelorum new combination, and Espadarana fernandoi new combination. PMID- 25112429 TI - Extending statistical boosting. An overview of recent methodological developments. AB - BACKGROUND: Boosting algorithms to simultaneously estimate and select predictor effects in statistical models have gained substantial interest during the last decade. OBJECTIVES: This review highlights recent methodological developments regarding boosting algorithms for statistical modelling especially focusing on topics relevant for biomedical research. METHODS: We suggest a unified framework for gradient boosting and likelihood-based boosting (statistical boosting) which have been addressed separately in the literature up to now. RESULTS: The methodological developments on statistical boosting during the last ten years can be grouped into three different lines of research: i) efforts to ensure variable selection leading to sparser models, ii) developments regarding different types of predictor effects and how to choose them, iii) approaches to extend the statistical boosting framework to new regression settings. CONCLUSIONS: Statistical boosting algorithms have been adapted to carry out unbiased variable selection and automated model choice during the fitting process and can nowadays be applied in almost any regression setting in combination with a large amount of different types of predictor effects. PMID- 25112430 TI - A formative evaluation of the implementation of an upper limb stroke rehabilitation intervention in clinical practice: a qualitative interview study. AB - BACKGROUND: The Graded Repetitive Arm Supplementary Program (GRASP) is a hand and arm exercise programme designed to increase the intensity of exercise achieved in inpatient stroke rehabilitation. GRASP was shown to be effective in a randomised controlled trial in 2009 and has since experienced unusually rapid uptake into clinical practice. The aim of this study was to conduct a formative evaluation of the implementation of GRASP to inform the development and implementation of a similar intervention in the United Kingdom. METHODS: Semi-structured interviews were conducted with therapists who were involved in implementing GRASP at their work site, or who had experience of using GRASP. Normalisation Process Theory (NPT), a sociological theory used to explore the processes of embedding innovations in practice, was used to develop an interview guide. Intervention components outlined within the GRASP Guideline Manual were used to develop prompts to explore how therapists use GRASP in practice. Interview transcripts were analysed using a coding frame based on implementation theory. RESULTS: Twenty interviews were conducted across eight sites in British Columbia Canada. Therapists identified informal networks and the free online availability of GRASP as key factors in finding out about the intervention. All therapists reported positive opinions about the value of GRASP. At all sites, therapists identified individuals who advocated for the use of GRASP, and in six of the eight sites this was the practice leader or senior therapist. Rehabilitation assistants were identified as instrumental in delivering GRASP in almost all sites as they were responsible for organising the GRASP equipment and assisting patients using GRASP. Almost all intervention components were found to be adapted to some degree when used in clinical practice; coverage was wider, the content adapted, and the dose, when monitored, was less. CONCLUSIONS: Although GRASP has translated into clinical practice, it is not always used in the way in which it was shown to be effective. This formative evaluation has informed the development of a novel intervention which aims to bridge this evidence-practice gap in upper limb rehabilitation after stroke. PMID- 25112431 TI - Reducing the risk of bias in health behaviour change trials: improving trial design, reporting or bias assessment criteria? A review and case study. AB - OBJECTIVE: It has been suggested that randomised controlled trials (RCTs) of health behaviour change (HBC) interventions are less rigorously designed than - for example- drug trials. This study presents an approach to clarifying whether this is due to poor trial design, incomplete trial reporting and/or the inappropriateness of commonly applied risk of bias assessment criteria. DESIGN: First, a framework of key sources of bias and common strategies for reducing bias risk is developed based on a literature review. Second, we describe the design of a multi-site RCT evaluating the cost-effectiveness of an HIV-treatment adherence intervention (case study). The choices made by the multidisciplinary team trying to minimise the risk of bias are compared against the risk of bias framework. MAIN OUTCOME MEASURES: Implementation of common strategies for reducing the risk of bias in the case study; alternative or additional strategies applied; a justification for each deviation from the risk of bias framework. RESULTS: Most of the common strategies for reducing the risk of bias could be implemented. Alternative strategies were developed for minimising the risk of performance bias and contamination. Several additional, domain-specific risk of bias strategies were implemented. CONCLUSIONS: The literature provides useful guidance for reducing the risk of bias in HBC trials. Yet, the case study suggests that HBC trial designers may face specific challenges that require alternative/additional measures for reducing the risk of bias. Using the risk of bias justification table (RATIONALE) could lead to better-designed HBC trials, more comprehensive trial reports and the data necessary for evaluating the appropriateness of commonly applied risk of bias assessment criteria to HBC trials. PMID- 25112432 TI - Experiences of and responses to disrespectful maternity care and abuse during childbirth; a qualitative study with women and men in Morogoro Region, Tanzania. AB - BACKGROUND: Interventions to reduce maternal mortality have focused on delivery in facilities, yet in many low-resource settings rates of facility-based birth have remained persistently low. In Tanzania, rates of facility delivery have remained static for more than 20 years. With an aim to advance research and inform policy changes, this paper builds on a growing body of work that explores dimensions of and responses to disrespectful maternity care and abuse during childbirth in facilities across Morogoro Region, Tanzania. METHODS: This research drew on in-depth interviews with 112 respondents including women who delivered in the preceding 14 months, their male partners, public opinion leaders and community health workers to understand experiences with and responses to abuse during childbirth. All interviews were recorded, transcribed, translated and coded using Atlas.ti. Analysis drew on the principles of Grounded Theory. RESULTS: When initially describing birth experiences, women portrayed encounters with providers in a neutral or satisfactory light. Upon probing, women recounted events or circumstances that are described as abusive in maternal health literature: feeling ignored or neglected; monetary demands or discriminatory treatment; verbal abuse; and in rare instances physical abuse. Findings were consistent across respondent groups and districts. As a response to abuse, women described acquiescence or non-confrontational strategies: resigning oneself to abuse, returning home, or bypassing certain facilities or providers. Male respondents described more assertive approaches: requesting better care, paying a bribe, lodging a complaint and in one case assaulting a provider. CONCLUSIONS: Many Tanzanian women included in this study experienced unfavorable conditions when delivering in facilities. Providers, women and their families must be made aware of women's rights to respectful care. Recommendations for further research include investigations of the prevalence and dimensions of disrespectful care and abuse, on mechanisms for women and their families to effectively report and redress such events and on interventions that could mitigate neglect or isolation among delivering women. Respectful care is a critical component to improve maternal health. PMID- 25112433 TI - Impact of pre-imputation SNP-filtering on genotype imputation results. AB - BACKGROUND: Imputation of partially missing or unobserved genotypes is an indispensable tool for SNP data analyses. However, research and understanding of the impact of initial SNP-data quality control on imputation results is still limited. In this paper, we aim to evaluate the effect of different strategies of pre-imputation quality filtering on the performance of the widely used imputation algorithms MaCH and IMPUTE. RESULTS: We considered three scenarios: imputation of partially missing genotypes with usage of an external reference panel, without usage of an external reference panel, as well as imputation of completely un typed SNPs using an external reference panel. We first created various datasets applying different SNP quality filters and masking certain percentages of randomly selected high-quality SNPs. We imputed these SNPs and compared the results between the different filtering scenarios by using established and newly proposed measures of imputation quality. While the established measures assess certainty of imputation results, our newly proposed measures focus on the agreement with true genotypes. These measures showed that pre-imputation SNP filtering might be detrimental regarding imputation quality. Moreover, the strongest drivers of imputation quality were in general the burden of missingness and the number of SNPs used for imputation. We also found that using a reference panel always improves imputation quality of partially missing genotypes. MaCH performed slightly better than IMPUTE2 in most of our scenarios. Again, these results were more pronounced when using our newly defined measures of imputation quality. CONCLUSION: Even a moderate filtering has a detrimental effect on the imputation quality. Therefore little or no SNP filtering prior to imputation appears to be the best strategy for imputing small to moderately sized datasets. Our results also showed that for these datasets, MaCH performs slightly better than IMPUTE2 in most scenarios at the cost of increased computing time. PMID- 25112434 TI - Prostate cancer in a man with a BRCA2 mutation and a personal history of bilateral breast cancer. AB - Men with a BRCA2 mutation face substantial lifetime risks for the development of both breast and prostate cancer. A male who was initially diagnosed with breast cancer at the age of 32 was subsequently diagnosed at age 77 with both contralateral breast cancer and prostate cancer. He was found to be BRCA2 mutation carrier. The patient was treated with contralateral mastectomy, breast irradiation, prostate irradiation and adjuvant endocrine therapy. At age 83 he died of metastatic prostate cancer. Our case underscores the observation that BRCA2 mutation carriers are at risk for multiple cancers, including contralateral breast cancer, and illustrates the need for current practice recommendations for the early detection of breast and prostate cancer in men with BRCA2 mutations. PMID- 25112435 TI - Accumulation of cadmium in and its effect on the midgut gland of terrestrial snail Helix pomatia L. from urban areas in Poland. AB - The objectives of this study were (1) to determine cadmium (Cd) accumulation in the midgut gland of a land snail Helix pomatia L. inhabiting residential areas of the 14 largest cities in Poland, and (2) to examine whether the accumulated Cd exerted any toxic effects. The average accumulation of Cd in the midgut gland of snails, weighing 16-18 g, ranged from 7.00 to 87.3 ug/g dry weight (0.06-0.77 umol/g) and differed significantly among animals from the various urban areas. This difference in Cd accumulation was not related to city population, but was associated with the topsoil Cd (R(2) = 0.868, p < 0.0001). The tissue Cd was not found to produce toxicity (histopathology, programmed cell death, lipofuscin formation or lipid peroxidation), probably due to the induction of sufficiently high quantities of metallothionein and glutathione, well-known protective molecules. PMID- 25112436 TI - YLT192, a novel, orally active bioavailable inhibitor of VEGFR2 signaling with potent antiangiogenic activity and antitumor efficacy in preclinical models. AB - Antagonizing vascular endothelial growth factor receptor 2 (VEGFR2) to block angiogenesis has been applied toward cancer therapy for its role in promoting cancer growth and metastasis. However, most these clinical anticancer drugs have unexpected side effects. Development of novel VEGFR2 inhibitors with less toxicity remains an urgent need. In this study, we describe a novel, well tolerated, and orally active VEGFR2 inhibitor, YLT192, which inhibits tumor angiogenesis and growth. YLT192 significantly inhibited kinase activity of VEGFR2 and suppressed proliferation, migration, invasion, and tube formation of human umbilical vascular endothelial cells (HUVEC) in vitro. In addition, it inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream signaling regulator in HUVEC. Zebrafish embryonic models and alginate-encapsulated tumor cell assays indicated YLT192 also inhibited angiogenesis in vivo. Moreover, YLT192 could directly inhibit proliferation and induce apoptosis of cancer cells in vitro and in vivo. Oral administration of YLT192 at a dose of 100 mg/kg/day could markedly inhibited human tumor xenograft growth without causing obvious toxicities. It decreased microvessel densities (MVD) in tumor sections. It also shows good safety profiles in the studies with mice and rats. Taken together, these preclinical evaluations suggest that YLT192 inhibits angiogenesis and may be a promising anticancer drug candidate. PMID- 25112440 TI - Cystic kidney disease: Intracellular clusterin implicated in nephropathic cystinosis. PMID- 25112438 TI - Child Eating Behaviors and Caregiver Feeding Practices in Children with Autism Spectrum Disorders. AB - OBJECTIVE: This pilot study compared children with autism spectrum disorders (ASD) and typically developing children (TDC) on weight-related outcomes and caregiver-reported child eating behaviors and feeding practices. DESIGN AND SAMPLE: Cross-sectional study. Caregivers of 25 children with ASD and 30 TDC, ages 4-6. METHODS: Caregivers completed validated questionnaires that assessed child eating behaviors and feeding practices. Children's height, weight, and waist circumference were measured. RESULTS: Children with ASD, when compared to TDC, showed significantly greater abdominal waist circumferences (p = .01) and waist-to-height ratios (p < .001). Children with ASD with atypical oral sensory sensitivity exhibited greater food avoidance behaviors, including reluctance to eat novel foods (p = .004), being selective about the range of foods they accept (p = .03), and undereating due to negative emotions (p = .02), than children with ASD with typical oral sensory sensitivity. Caregivers of children with ASD with atypical oral sensory sensitivity reported using food to regulate negative child emotions to a greater extent than caregivers of children with typical oral sensory sensitivity (p = .02). DISCUSSION: Children with ASD, especially those with atypical oral sensory sensitivity, are at increased risk for food avoidance behaviors and may require additional support in several feeding domains. PMID- 25112437 TI - Proanthocyanidins from grape seeds inhibit UV-radiation-induced immune suppression in mice: detection and analysis of molecular and cellular targets. AB - Ultraviolet (UV)-radiation-induced immunosuppression has been linked with the risk of skin carcinogenesis. Approximately, 2 million new cases of skin cancers, including melanoma and nonmelanoma, diagnosed each year in the USA and therefore have a tremendous bad impact on public health. Dietary phytochemicals are promising options for the development of effective strategy for the prevention of photodamaging effects of UV radiation including the risk of skin cancer. Grape seed proanthocyanidins (GSPs) are such phytochemicals. Dietary administration of GSPs with AIN76A control diet significantly inhibits UV-induced skin tumor development as well as suppression of immune system. UV-induced suppression of immune system is commonly determined using contact hypersensitivity (CHS) model which is a prototype of T-cell-mediated immune response. We present evidence that inhibition of UV-induced suppression of immune system by GSPs is mediated through: (i) the alterations in immunoregulatory cytokines, interleukin (IL)-10 and IL-12, (ii) DNA repair, (iii) stimulation of effector T cells and (iv) DNA repair-dependent functional activation of dendritic cells in mouse model. These information have important implications for the use of GSPs as a dietary supplement in chemoprevention of UV-induced immunosuppression as well as photocarcinogenesis. PMID- 25112443 TI - Would medical students enter an exclusion zone in an infected district with a high mortality rate? An analysis of book reports on 28 (secondary publication). AB - This study aimed to ascertain whether medical students would enter a closed area where there was a raging epidemic of an infectious disease with a high fatality rate, and includes reasons for the students entering or refusing to enter. Participants included 50 second-year medical students. They were assigned to read a novel entitled 28, written by Youjeong Jeong, and discuss it in groups. Using their book reports, their decisions of whether or not to enter Hwayang, the city from the novel, and the reasons for their decisions were analyzed; we furthermore investigated the factors affecting their decisions. Among the 50 respondents, 18 students (36%) answered that they would enter, and the remaining 32 students (64%) answered that they would not enter the zone. The reasons given for entering were responsibility (44%), sense of ethics (33%), social duty (17%), and sense of guilt (6%). The reasons the students provided for not entering were inefficiency (44%), worry regarding family (28%), needlessness of sacrifice (19%), and safety not ensured (9%). Students who had four or fewer family members were more likely to enter Hwayang than were students who had five or more family members (odds ratio, 1.85). Students who had completed over 100 hours of volunteer work were more likely to enter Hwayang than were students who had volunteered less than 100 hours (odds ratio, 2.04). Owing to their "responsibility" as a doctor, 36% of medical students answered that they would enter an exclusion zone in an infected district with a high fatality rate. However, 64% answered they would not enter because of "inefficiency." For the medical students it is still a question 'To enter or not to enter?' PMID- 25112441 TI - Transplantation: Alemtuzumab induction reduces acute rejection risk. PMID- 25112444 TI - Is a medical humanities test needed in the National Medical Licensing Examination of Korea? Opinions of medical students and physician writers (secondary publication). AB - The purpose of this study was to examine the opinions of medical students and physician writers regarding the medical humanities as a subject and its inclusion in the medical school curriculum. Furthermore, we addressed whether an assessment test should be added to the National Medical Licensing Examination of Korea (KMLE). A total of 192 medical students at Inha University and 39 physician writers registered with the Korean Association of Physician Essayists and the Korean Association of Physician Poets participated in this study. They were asked to answer a series of questionnaires. Most medical students (59%) and all physician writers (100%) answered that the medical humanities should be included in the medical school curriculum to train good physicians. They thought that the KMLE did not currently include an assessment of the medical humanities (medical students 69%, physician writers 69%). Most physician writers (87%; Likert scale, 4.38+/-0.78) felt that an assessment of the medical humanities should be included in the KMLE. Half of the medical students (51%; Likert scale, 2.51+/-1.17) were against including it in the KMLE, which they would have to pass after several years of study. For the preferred field of assessment, medical ethics was the most commonly endorsed subject (medical students 59%, physician writers 39%). The most frequently preferred evaluation method was via an interview (medical students 45%, physician writers 33%). In terms of the assessment of the medical humanities and the addition of this subject to the KMLE, an interview-based evaluation should be developed. PMID- 25112446 TI - Documentary research and evaluation in medical education. PMID- 25112447 TI - Assessing the reliability and validity of the Revised Two Factor Study Process Questionnaire (R-SPQ2F) in Ghanaian medical students. AB - PURPOSE: We investigated the validity and reliability of the Revised Two Factor Study Process Questionnaire (R-SPQ2F) in preclinical students in Ghana. METHODS: The R-SPQ2F was administered to 189 preclinical students of the University for Development Studies, School of Medicine and Health Sciences. Both descriptive and inferential statistics with Cronbach's alpha test and factor analysis were done. RESULTS: The mean age of the students was 22.69+/- 0.18years, 60.8% (n=115) were males and 42.3% (n=80) were in their second year of medical training. The students had higher mean deep approach scores (31.23+/-7.19) than that of surface approach scores (22.62+/-6.48). Findings of the R-SPQ2F gave credence to a solution of two-factors indicating deep and surface approaches accounting for 49.80% and 33.57%, respectively, of the variance. The scales of deep approach (Cronbach's alpha, 0.80) and surface approach (Cronbach's alpha, 0.76) and their subscales demonstrated an internal consistency that was good. The factorial validity was comparable to other studies. CONCLUSION: Our study confirms the construct validity and internal consistency of the R-SPQ2F for measuring approaches to learning in Ghanaian preclinical students. Deep approach was the most dominant learning approach among the students. The questionnaire can be used to measure students' approaches to learning in Ghana and in other African countries. PMID- 25112445 TI - Confounding factors in using upward feedback to assess the quality of medical training: a systematic review. AB - PURPOSE: Upward feedback is becoming more widely used in medical training as a means of quality control. Multiple biases exist, thus the accuracy of upward feedback is debatable. This study aims to identify factors that could influence upward feedback, especially in medical training. METHODS: A systematic review using a structured search strategy was performed. Thirty-five databases were searched. Results were reviewed and relevant abstracts were shortlisted. All studies in English, both medical and non-medical literature, were included. A simple pro-forma was used initially to identify the pertinent areas of upward feedback, so that a focused pro-forma could be designed for data extraction. RESULTS: A total of 204 articles were reviewed. Most studies on upward feedback bias were evaluative studies and only covered Kirkpatrick level 1-reaction. Most studies evaluated trainers or training, were used for formative purposes and presented quantitative data. Accountability and confidentiality were the most common overt biases, whereas method of feedback was the most commonly implied bias within articles. CONCLUSION: Although different types of bias do exist, upward feedback does have a role in evaluating medical training. Accountability and confidentiality were the most common biases. Further research is required to evaluate which types of bias are associated with specific survey characteristics and which are potentially modifiable. PMID- 25112448 TI - Reflective writing and its impact on empathy in medical education: systematic review. AB - PURPOSE: Medical schools are increasingly aware of the ways in which physician empathy can have a profound impact on patients' lives and have developed humanities initiatives to address this concern. Reflective writing in particular is more commonly promoted in medical curricula, but there is limited research on the impact of reflective writing on medical student empathy levels. It aims to find the emotional effects of reflective writing interventions on medical and healthcare students by systemic review. METHODS: Two investigators independently reviewed educational publications for critical analysis. This review focused systematically on quantitative papers that measure the impact of reflective writing on empathy. RESULTS: Of the 1,032 studies found on Medline and CINAHL, only 8 used quantitative measures pre- and postwritten reflection to measure any impact on empathy outcomes. The outcomes measured included impact of reflective writing exercises on student wellness, aptitude, and/or clinical skills. Of these studies, a significant change in student empathy was observed in 100% of the studies, demonstrating a significant change in outcomes. CONCLUSION: Although the lack of homogeneity in outcome measurement in the literature limits possible conclusion from this review, the overwhelmingly positive reporting of outcomes suggests that reflective writing should be considered in any medical curriculum. PMID- 25112449 TI - Strengthening student communication through pediatric simulated patient encounters. AB - As medical students enter the role of physician, clinical outcomes not only rely on their mastery of clinical knowledge, but also on the effectiveness in which they can communicate with patients and family members. While students typically have numerous opportunities to practice clinical communication with adult patients, such practice in pediatric settings is limited. This study examines if simulated patient (SP) encounters strengthen third-year medical students' communication skills during the pediatrics clerkship. During 2011-2013, three SP encounters (comprising 3 pediatric scenarios) were incorporated into a pediatrics clerkship at one United States medical school to give students a safe venue to practice advanced communication with observation and direct feedback. Third-year medical students engaged in the scenarios and received both written and oral feedback from an evaluator observing the encounter. With IRB approval, students' self-perceived confidence and abilities at performing the advanced communication skills were measured using an eightitem, Likert scale questionnaire administered pre and post the SP encounter. Pre- and post-questionnaires (n=215; response rate, 96%) analyzed using a Wilcoxon-matched pairs signed-rank test demonstrated statistically significant increases in students' perception of their confidence and abilities regarding their performance (P<0.05; Bonferroni correction, P<0.006). There was an increases in student confidence and self-perceived ability in: first, communicating with children and family members of young patients; second, managing confrontational situations involving parents; third, performing a thorough psychosocial history with an adolescent; and fourth, using Evidence Based Medicine to motivate parents. PMID- 25112450 TI - Ranolazine treatment for myocardial infarction? Effects on the development of necrosis, left ventricular function and arrhythmias in experimental models. AB - Ranolazine, an inhibitor of the late current of the cardiac action potential (late I(Na)), is a well established clinical treatment for chronic angina. The late INa in cardiac myocytes also plays an important role in the pathophysiology of acute myocardial ischemia and reperfusion, and thus is a potential therapeutic target to ameliorate consequences of myocardial infarction. In experimental animal models, ranolazine has been shown to reduce myocardial infarct size, improve left ventricular function, decrease ischemia/reperfusion-induced arrhythmias and improve outcome in heart failure. Here we focus specifically on data from in vivo animal studies of myocardial ischemia and reperfusion. PMID- 25112452 TI - Thermal human biometeorological conditions and subjective thermal sensation in pedestrian streets in Chengdu, China. AB - The outdoor thermal environment of a public space is highly relevant to the thermal perception of individuals, thereby affecting the use of space. This study aims to connect thermal human biometeorological conditions and subjective thermal sensation in hot and humid regions and to find its influence on street use. We performed a thermal comfort survey at three locations in a pedestrian precinct of Chengdu, China. Meteorological measurements and questionnaire surveys were used to assess the thermal sensation of respondents. The number of people visiting the streets was counted. Meanwhile, mean radiant temperature (T mrt) and the physiological equivalent temperature (PET) index were used to evaluate the thermal environment. Analytical results reveal that weather and street design drive the trend of diurnal micrometeorological conditions of the street. With the same geometry and orientation, a street with no trees had wider ranges of meteorological parameters and a longer period of discomfort. The neutral temperature in Chengdu (24.4 degrees C PET) is similar to that in Taiwan, demonstrating substantial human tolerance to hot conditions in hot and humid regions. Visitors' thermal sensation votes showed the strongest positive relationships with air temperature. Overall comfort level was strongly related to every corresponding meteorological parameter, indicating the complexity of people's comfort in outdoor environments. In major alleys with multiple functions, the number of people in the street decreased as thermal indices increased; T mrt and PET had significant negative correlations with the number of people. This study aids in understanding pedestrian street use in hot and humid regions. PMID- 25112453 TI - Efficacy of daptomycin lock therapy in the treatment of bloodstream infections related to long-term catheter. AB - BACKGROUND: Concomitant systemic and intracatheter antibiotic therapy is a therapeutic option for catheter-related bloodstream infections (CRBSI) in patient fitted with long-term intravenous central catheters. CRBSI are mainly caused by Gram-positive bacteria. Daptomycin (DPT) is an antibiotic active against Gram positive bacteria with high bactericidal activity and good biofilm penetration. OBJECTIVE: To study the efficacy of DPT given systemically and as lock therapy in the treatment of CRBSI. MATERIALS AND METHODS: A retrospective review was conducted of adult patients with a long-term central venous catheter (CVC) receiving both systemic intravenous and intracatheter lock therapy for CRBSI. The primary outcome was catheter maintenance, following clinical success and microbiological eradication. RESULTS: Eight patients who had failed previous standard therapy (vancomycin 7, cefazolin 1) were included in the study. In all but one, coagulase-negative staphylococci were repeatedly isolated. The other patient had enterococcal infection. DPT, given intravenously and as lock therapy, was successful in six of eight cases. The mean time to negative blood cultures was 2 days (range 1-6). In two cases neither clinical nor microbiological response was documented and the catheter was removed. DISCUSSION: Systemic and intracatheter therapy with DPT is feasible, carries no toxicity and is apparently effective. DPT might be a suitable therapeutic option in CRBSI to achieve CVC sterilization and preserve the catheter. PMID- 25112454 TI - Navigated three-dimensional T1-weighted gradient-echo sequence for gadoxetic acid liver magnetic resonance imaging in patients with limited breath-holding capacity. AB - PURPOSE: To determine whether a navigator-gated three-dimensional T1-weighted gradient-echo sequence (T1W-GRE, navigated LAVA) can improve diagnostic performance for the detection of focal liver lesions (FLLs) compared to standard breath-hold (BH) T1W-GRE breath-hold LAVA (BH-LAVA) during the hepatobiliary phase (HBP) of gadoxetic acid liver magnetic resonance imaging (MRI) in patients with limited breath-holding capacity. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board and the requirement for informed consent was waived. We included 372 patients who underwent liver MRI including both navigated LAVA and BH-LAVA sequences. Overall image quality of the two HBP image sets was compared. In patients with limited breath-holding capacity, diagnostic performances in detecting FLLs on the two HBP images were compared using jackknife-alternative free-response receiver-operating characteristic (JAFROC) analysis by two reviewers. RESULTS: There were 13 cases (13/372; 3.5%) of image acquisition failure using the navigated LAVA sequence due to severe irregular breathing, and 50 of 359 patients had limited breath-holding capacity. In these patients, overall image quality of navigated LAVA (2.78 +/- 0.95) was significantly better than that of BH-LAVA (2.42 +/- 0.81, P < 0.005), and both readers showed significantly higher JAFROC figure-of-merit values with navigated LAVA compared to BH-LAVA (0.94 and 0.86 in reviewer 1, respectively; 0.89 and 0.83 in reviewer 2, respectively, P < 0.005). Overall image quality of navigated LAVA was also better than that of BH-LAVA in patients with sufficient breath-holding capacity (n = 309, 3.96 +/- 0.88, 3.81 +/- 0.66, respectively, P < 0.001). CONCLUSION: The navigated LAVA sequence could provide better image quality and diagnostic performance in detecting FLLs than BH-LAVA in patients with limited breath-holding capacity during HBP of gadoxetic acid MRI. PMID- 25112457 TI - Drug-target interaction prediction via chemogenomic space: learning-based methods. AB - INTRODUCTION: Identification of the interaction between drugs and target proteins is a crucial task in genomic drug discovery. The in silico prediction is an appropriate alternative for the laborious and costly experimental process of drug target interaction prediction. Developing a variety of computational methods opens a new direction in analyzing and detecting new drug-target pairs. AREAS COVERED: In this review, we will focus on chemogenomic methods which have established a learning framework for predicting drug-target interactions. Learning-based methods are classified into supervised and semi-supervised, and the supervised learning methods are studied as two separate parts including similarity-based methods and feature-based methods. EXPERT OPINION: In spite of many improvements for pharmacology applications by learning-based methods, there are many over simplification settings in construction of predictive models that may lead to over-optimistic results on drug-target interaction prediction. PMID- 25112455 TI - Efficient production of single-chain fragment variable-based N-terminal trimerbodies in Pichia pastoris. AB - BACKGROUND: Recombinant antibodies are highly successful in many different pathological conditions and currently enjoy overwhelming recognition of their potential. There are a wide variety of protein expression systems available, but almost all therapeutic antibodies are produced in mammalian cell lines, which mimic human glycosylation. The production of clinical-grade antibodies in mammalian cells is, however, extremely expensive. Compared to mammalian systems, protein production in yeast strains such as Pichia pastoris, is simpler, faster and usually results in higher yields. RESULTS: In this work, a trivalent single chain fragment variable (scFv)-based N-terminal trimerbody, specific for the human carcinoembryonic antigen (CEA), was expressed in human embryonic kidney 293 cells and in Pichia pastoris. Mammalian- and yeast-produced anti-CEA trimerbody molecules display similar functional and structural properties, yet, the yield of trimerbody expressed in P. pastoris is about 20-fold higher than in human cells. CONCLUSIONS: P. pastoris is an efficient expression system for multivalent trimerbody molecules, suitable for their commercial production. PMID- 25112458 TI - The frequency of re-planning and its variability dependent on the modification of the re-planning criteria and IGRT correction strategy in head and neck IMRT. AB - BACKGROUND: To analyse the frequency of re-planning and its variability dependent on the IGRT correction strategy and on the modification of the dosimetric criteria for re-planning for the spinal cord in head and neck IG-IMRT. METHODS: Daily kV-control-CTs of six head and neck patients (=175 CTs) were analysed. All volumes of interest were re-contoured using deformable image registration. Three IGRT correction strategies were simulated and the resulting dose distributions were computed for all fractions. Different sets of criteria with varying dose thresholds for re-planning were investigated. All sets of criteria ensure equivalent target coverage of both CTVs, but vary in the tolerance threshold of the spinal cord. RESULTS: The variations of the D95 and D2 in respect to the planned values ranged from -7% to +3% for both CTVs, and -2% to +6% for the spinal cord. Despite different correction vectors of the three IGRT strategies, the dosimetric differences were small. The number of fractions not requiring re planning varied between 0% and 11% dependent on the applied IGRT correction strategy. In contrast, this number ranged between 32% and 70% dependent on the dosimetric thresholds, even though these thresholds were only gently modified. CONCLUSIONS: The more precise the planned dose needs to be maintained over the treatment course, the more frequently re-planning is required. The influence of different IGRT correction strategies, even though geometrically notable, was found to be of only limited relevance for the re-planning frequency. In contrast, the definition and modification of thresholds for re-planning have a major impact on the re-planning frequency. PMID- 25112459 TI - Month-wise estimates of tobacco smoking during pregnancy for the United States, 2002-2009. AB - The timing of prenatal exposure to tobacco cigarette smoking can be crucial for the developing fetus. Pushing the field beyond prior pregnancy trimester-focused smoking estimates, we estimated month-specific prevalence proportions for tobacco cigarette smoking among pregnant and non-pregnant women of the United States, with consideration of tobacco dependence (TD) as well. In advance, we posited that pregnancy onset might prompt smoking cessation in early months, before the end of the 1st trimester, and that TD might account for sustained smoking in later months, especially months 8-9, when there are added reasons to quit. Estimates are from the 2002-2009 National Surveys on Drug Use and Health Restricted-Data Analysis System (R-DAS), with large nationally representative samples of US civilians, including 12-44 year old women (n ~ 70,000) stratified by pregnancy status and month of pregnancy, with multi-item assessment of TD as well as recently active smoking. Age was held constant via the Breslow-Day indirect standardization approach, a methodological detail of potential interest to other research teams conducting online R-DAS analyses. Among 12-44 year old women in Month 1 of pregnancy, as well as non-pregnant women, just over one in four was a recently active smoker (26-27 %), and approximately one-half of these smokers qualified as a TD case (52 %). Corresponding estimates for women in Month 3 were 17.6 % and two-thirds, respectively, lending some support for our advance hypotheses. Nonetheless, our a priori TD hypothesis about Months 8-9 seems to be contradicted: an increased concentration of TD among smokers surfaced early in pregnancy. Evidence of a possible ameliorative pregnancy effect on smoking prevalence as well as TD's effect on smoking persistence might be seen quite early in pregnancy. Substitution of a month-specific view for the traditional trimester view sheds new light on how pregnancy might shape smoking behavior before the end of trimester 1, with TD seeming to thwart a public health goal of 100 % cessation, early in pregnancy. PMID- 25112451 TI - Evaluation of the impact of implementing the emergency medical services traumatic brain injury guidelines in Arizona: the Excellence in Prehospital Injury Care (EPIC) study methodology. AB - Traumatic brain injury (TBI) exacts a great toll on society. Fortunately, there is growing evidence that the management of TBI in the early minutes after injury may significantly reduce morbidity and mortality. In response, evidence-based prehospital and in-hospital TBI treatment guidelines have been established by authoritative bodies. However, no large studies have yet evaluated the effectiveness of implementing these guidelines in the prehospital setting. This article describes the background, design, implementation, emergency medical services (EMS) treatment protocols, and statistical analysis of a prospective, controlled (before/after), statewide study designed to evaluate the effect of implementing the EMS TBI guidelines-the Excellence in Prehospital Injury Care (EPIC) study (NIH/NINDS R01NS071049, "EPIC"; and 3R01NS071049-S1, "EPIC4Kids"). The specific aim of the study is to test the hypothesis that statewide implementation of the international adult and pediatric EMS TBI guidelines will significantly reduce mortality and improve nonmortality outcomes in patients with moderate or severe TBI. Furthermore, it will specifically evaluate the effect of guideline implementation on outcomes in the subgroup of patients who are intubated in the field. Over the course of the entire study (~9 years), it is estimated that approximately 25,000 patients will be enrolled. PMID- 25112460 TI - Therapeutic options after treatment failure in rheumatoid arthritis or spondyloarthritides. AB - The prognosis for patients with rheumatoid arthritis or spondyloarthritides has improved dramatically due to earlier diagnosis, recognition of the need to treat early with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), alone or in combinations, the establishment of treatment targets, and the development of biological DMARDs (bDMARDs). Many patients are now able to achieve clinical remission or low disease activity with therapy, and reduce or eliminate systemic corticosteroid use. Guidelines recommend methotrexate as a first-line agent for the initial treatment of rheumatoid arthritis; however, a majority of patients will require a change of csDMARD or step up to combination therapy with the addition of another csDMARD or a bDMARD. However, treatment failure is common and switching to a different therapy may be required. The large number of available treatment options, combined with a lack of comparative data, makes the choice of a new therapy complex and often not evidence based. We summarize and discuss evidence to inform treatment decisions in patients who require a change in therapy, including baseline factors that may predict response to therapy. PMID- 25112461 TI - Comparing patient outcomes of academician-preceptors, hospitalist-preceptors, and hospitalists on internal medicine services in an academic medical center. AB - BACKGROUND: Patient outcomes with hospitalist care have been studied in many settings, yet little is known about how hospitalist care interacts with trainee care to affect patient outcomes in teaching hospitals. OBJECTIVES: The aim of this study was to compare patient outcomes between hospitalist-preceptors and hospitalists working alone (isolating the effect of housestaff involvement), and between hospitalist-preceptors and academician-preceptors (isolating the effect of attending type, given housestaff involvement). DESIGN: A four-year retrospective cohort study of patients (n = 13,313) admitted to all internal medicine services at an academic medical center from July 2008 to June 2012. MAIN MEASURES: Using generalized estimating equations, we measured readmission within 30 days, hospital length of stay, cost of the index hospitalization, and cumulative cost including readmissions within 30 days. KEY RESULTS: In the adjusted models, 30-day readmission odds were higher for academic-preceptors (OR, 1.14 [95% CI, 1.03 - 1.26]) and hospitalist-preceptors (OR, 1.10 [95% CI, 1.002 - 1.21]) than for hospitalists working alone. Compared with hospitalists working alone, academic-preceptors were associated with shorter length of stay (mean difference, 0.27 days [95% CI, 0.18 - 0.38]), lower index hospitalization costs (mean difference, $386 [95% CI, $192 - $576]), but similar cumulative inpatient costs within 30 days of discharge. Compared with hospitalists working alone, hospitalist-preceptors were associated with shorter length of stay (mean difference, 0.34 days [95% CI, 0.26 - 0.42]), lower index hospitalization cost (mean difference, $570 [95% CI, $378 - $760]), and a trend toward lower cumulative cost (mean difference, $1347 [95% CI, $254 - $2,816]). CONCLUSIONS: Preceptor-led medicine services were associated with more readmissions within 30 days, shorter lengths of stay, and lower index admission-associated costs. However, when considering cumulative hospitalization costs, patients discharged by academician-preceptors incurred the highest cost and hospitalist-preceptors incurred the lowest cost. PMID- 25112462 TI - Gender differences in resources and negotiation among highly motivated physician scientists. AB - BACKGROUND: Resources, including space, equipment, funding, personnel, and protected time, are essential in academic medical careers. Negotiation often plays a key role in the distribution of these resources. OBJECTIVE: This study explored gender differences in resources, negotiation behaviors, and negotiation outcomes in a sample of career development awardees. DESIGN: Postal survey of a cohort of 1,708 clinician-researchers with responses from 1,275 (75 % response rate). PARTICIPANTS: Researchers who received NIH K08 or K23 awards between 2006 and 2009. MAIN MEASURES: We analyzed gender differences in resources, negotiation behaviors, and negotiation outcomes, using regression models adjusted for race, K award type, K award year, degree, academic rank, specialty, and institutional funding. KEY RESULTS: Over one-fifth of respondents reported inadequate access to research space and one-third had asked for increased space or equipment. Perceived adequacy of these physical resources did not differ significantly by gender, but a higher proportion of women reported inadequate access to grants administrators (34.8 %) and statistical support (49.9 %) than men (26.9 %; p = 0.002 and 43.4 %; p = 0.025, respectively). Women were more likely to have asked for reduction in clinical hours (24.1 % vs. 19.3 %; p = 0.02) and to have raised concerns about unfair treatment (50.2 % vs. 38.2 %; p < 0.001). Overall, 42.9 % of women and 35.9 % of men asked for a raise in the two years preceding the survey (p = 0.09), and among those who had asked for increased resources, the likelihood that the request was granted did not differ significantly by gender. CONCLUSION: Many career development award recipients report resource needs and negotiate for increased resources. Gender differences in perceived access to research support personnel exist even in this select cohort of K awardees. Institutions should provide appropriate training in negotiation and ensure adequate and equitable distribution of resources to promote academic success. PMID- 25112463 TI - The shift of segmental contribution ratio in patients with herniated disc during cervical lateral bending. AB - BACKGROUND: Abnormal intervertebral movements of spine have been reported to be associated with trauma and pathological conditions. The importance of objective spinal motion imaging assessment in the frontal plane was frequently underestimated. The clinical evaluation of the segmental motion contribution could be useful for detecting the motion pattern of individual vertebrae. Therefore the purpose of this study was to investigate the shift of segmental contribution ratio in patients with herniated disc during cervical lateral bending to provide additional insights to cervical biomechanics. METHODS: A total of 92 subjects (46 healthy adult subjects and 46 disc-herniated patients) were enrolled in this case-control study. The motion images during cervical lateral bending movements were digitized using a precise image protocol to analyze the intervertebral motion and contribution. RESULTS: Our results showed that the intervertebral angulation during cervical lateral bending for the C2/3 to C6/7 segments were 7.66 degrees +/-2.37 degrees , 8.37 degrees +/-2.11 degrees , 8.91 degrees +/-3.22 degrees , 7.19 degrees +/-2.29 degrees , 6.31 degrees +/-2.11 degrees , respectively for the healthy subjects. For the patients with herniated disc, the intervertebral angulation for the C2/3 to C6/7 segments were 6.87 degrees +/-1.67 degrees , 7.83 degrees +/-1.79 degrees , 7.73 degrees +/-2.71 degrees , 5.13 degrees +/-2.05 degrees , 4.80 degrees +/-1.93 degrees , respectively. There were significant angulation and translational differences between healthy subjects and the patients with herniated disc in the C5/6 and C6/7 segments (P=0.001-0.029). The segmental contributions of the individual vertebral segments were further analyzed. There was a significant increase in segmental contribution ratio of C3/4 (P=0.048), while a significant decrease in contribution ratio of C5/6 (P=0.037) was observed in the patients with herniated disc. Our results indicated that the segmental contribution shifted toward the middle cervical spine in the patients with herniated disc. CONCLUSIONS: The segmental contributions of cervical spine during lateral bending movement were first described based on the validated radiographic protocol. The detection of the shift of segmental contribution ratio could be helpful for the diagnosis the motion abnormality resulted from the disc or, facet pathologies, and arthritic changes of cervical spine. PMID- 25112464 TI - Synthesis and antiviral bioactivity of novel 3-((2-((1E,4E)-3-oxo-5-arylpenta-1,4 dien-1-yl)phenoxy)methyl)-4(3H)-quinazolinone derivatives. AB - A series of novel 3-((2-((1E,4E)-3-oxo-5-arylpenta-1,4-dien-1-yl)phenoxy)methyl) 4(3H)-quinazolinone derivatives were designed and synthesized. Antiviral bioassays indicated that a few of the compounds exhibited higher antiviral activities against tobacco mosaic virus (TMV) in vivo than the commercial agent ningnanmycin. In particular, compounds A5, A12, A25, and A27 possessed appreciable curative bioactivities on TMV in vivo, with 50% effective concentration values ranging from 132.25 to 156.10 MUg/mL. These values are superior to that of ningnanmycin (281.22 MUg/mL) and suggest that novel 4(3H) quinazolinone derivatives containing 1,4-pentadien-3-one moiety can effectively control TMV. Evaluation of the antiviral properties in field studies and the mechanisms underlying the enhanced antiviral activities of these derivatives are an interesting topic for future investigation. PMID- 25112465 TI - Use of combination antihypertensive therapy initiation in older Americans without prevalent cardiovascular disease. AB - OBJECTIVES: To describe new users of antihypertensive medications and identify predictors of combination therapy initiation in older Americans. DESIGN: Retrospective observational cohort study. SETTING: Population-based study using U.S. Medicare fee-for-service healthcare claims (2007-2010). PARTICIPANTS: Medicare beneficiaries aged 65 and older with no recent diagnoses, procedures, or medications for cardiovascular disease who newly initiated an antihypertensive therapy (n = 275,493; 210,605 initiated monotherapy, 64,888 initiated combination therapy). MEASUREMENTS: Multivariable Poisson regression was used to assess factors associated with initiation of combination therapy versus monotherapy, including participant characteristics, prescriber characteristics, and participant encounters with the healthcare system. RESULTS: Initiation of combination therapy increased from 21.9% in 2007 to 24.7% in 2010. The most frequently initiated combinations were angiotensin-converting enzyme inhibitors with thiazide (29.7%) and angiotensin II receptor antagonists with thiazide (18.7%). Blacks (prevalence ratio (PR) = 1.48, 95% confidence interval (CI) = 1.45-1.51 vs. whites), individuals seeing a generalist (PR = 1.10, 95% CI = 1.07 1.14), individuals seeing more than one doctor (PR = 3.38, 95% CI = 3.33-3.44), and participants with no pharmacy claims in the previous 6 months (PR = 1.34, 95% CI = 1.30-1.37 vs. >=3 unique drug classes) were more likely to initiate combination therapy, whereas those who had more outpatient visits in the previous 12 months were less likely to initiate combination therapy (per five visits, PR = 0.82, 95% CI = 0.80-0.83). CONCLUSION: Nearly one in four new users of antihypertensive medications aged 65 and older started treatment with combination therapy. Blacks, individuals living in the south, and those with fewer outpatient physician office visits were more likely to initiate combination therapy. Further research is needed to determine whether this approach to managing hypertension is being well targeted to individuals who will require combination treatment. PMID- 25112467 TI - The effect of proinflammatory cytokines on IL-17RA expression in NSCLC. AB - Interleukin-17 receptor (IL-17RA) is essential for proinflammatory cytokine IL-17 mediated pathogenesis of various tumors. IL-17RA is upregulated by some proinflammatory cytokines such as IL-21 and IL-15 and downregulated by IL-2, while the effect of IL-1beta, IL-6, IL-8, TNF-alpha on IL-17RA expression in non small cell lung caner (NSCLC) remains unknown. Our findings revealed that IL-17RA mRNA was increased in NSCLC tissues compared with the corresponding peritumor tissues (P = 0.0039) and high expression of IL-17RA protein in human NSCLC tissues was significantly associated with histological subtype, primary tumor size and clinical stages (P = 0.033, 0.033 and 0.011, respectively). IL-17RA mRNA expression was positively related to IL-1beta, IL-6, IL-8, TNF-alpha mRNA expression (P = 0.013, 0.0001, 0.002 and 0.010 respectively) in NSCLC tissues. Furthermore, IL-1beta, IL-6, IL-8, TNF-alpha upregulated IL-17RA mRNA and protein in A549 and H460 cells (all P < 0.05). It is suggested that IL-1beta, IL-6, IL-8, TNF-alpha promoted IL-17RA expression in NSCLC and they may involve in IL-17RA signaling in NSCLC. PMID- 25112468 TI - Outcomes of surgical treatment for gastric cancer patients: 11-year experience of a Chinese high-volume hospital. AB - Gastric cancer is one of the leading causes of cancer-related deaths worldwide. We report our experience with surgery-related parameters and survival outcomes at a single Chinese center. This study analyzed patients following gastric resection between 2000 and 2010, and overall survival was the primary end point. In this study, 1,936 patients who underwent gastrectomy were collected from 2000 to 2010. Curative gastrectomy (R0 resection) was performed in 86.6 % of patients. D1/D1+ lymphadenectomy was frequently performed from 2000 to 2005, and the proportion of D2/D2+ lymphadenectomy increased after 2006. The number of harvested lymph nodes was 10.1 +/- 6.0 in 2000 and increased to 28.0 +/- 10.5 in 2010. Serosa-invasive lesions (pT4) accounted for 67.9 % of all cases. The 1-year overall survival (OS), 2-year OS, and 3-year OS rates were 89, 74, and 63 %, respectively. Multivariate analysis identified R status, tumor location, macroscopic type, and tumor stage (pT stage and pN stage) as the independent risk factors for overall survival. The prognosis of gastric cancer patients in China remains dismal. To improve the survival outcomes, further efforts toward early detection and multi disciplinary treatment are needed. PMID- 25112470 TI - Dyspnoea and comorbidity contribute to anxiety and depression in interstitial lung disease. AB - BACKGROUND AND OBJECTIVES: Little is known about the prevalence of anxiety in interstitial lung disease (ILD), and the contributors to depression are not clear. The aim of this study was to determine the prevalence and predictors of anxiety and depression in people with ILD. METHODS: One hundred and twenty-four individuals with ILD (age 64 years (standard deviation 12), 48 idiopathic pulmonary fibrosis) participated. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale to determine likely cases and borderline cases. Associations with demographic data, respiratory function, 6-min walk and Modified Medical Research Council Dyspnoea Scale (MMRC) were examined. RESULTS: The prevalence of anxiety was 31%, with clinically significant anxiety in 12%. Depression was present in 23% of individuals, with 7% having clinically significant depression. Independent predictors of anxiety were a higher MMRC score (P = 0.005, odds ratio (OR) for case 2.60, 95% confidence interval 1.37 to 4.92) and higher nadir SpO2 during walking (P = 0.003, OR for case 1.16, 1.04 1.30). Independent predictors of depression were a higher MMRC score (P = 0.006, case OR 3.84, 1.25-11.78, borderline case OR 2.44, 1.14-5.19) and a greater number of comorbidities (P = 0.003, case OR 2.02, 0.97-4.21, borderline case OR 2.26, 1.30-3.93). CONCLUSIONS: Anxiety and depression are present in a significant minority of individuals with ILD. Dyspnoea and comorbidities are important contributors that may be amenable to intervention. PMID- 25112471 TI - NPHS2 variation in Chinese southern infants with late steroid-resistant nephrotic syndrome. AB - Abstract NPHS2 mutations are responsible for autosomal recessive familial steroid resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset and rapid progression to chronic renal insufficiency. This gene mutation is also responsible for an adolescent onset form of autosomal recessive familial FSGS with heavy proteinuria. Many infants with late steroid-resistant nephrotic syndrome (late SRNS) are prone to an implicated clinical and therapeutic course. The etiopathogenesis and the long-term prognosis of late SRNS remain obscure. Considering the similar steroid resistance between late and initial SRNS, analysis of NPHS2 variation was performed in 70 sporadic Chinese infants with late SRNS and 70 controls in the present study to investigate the possible role of NPHS2 gene in late SRNS. The variation analysis revealed three polymorphisms (288C > T heterozygous in exon 2, 954T > C heterozygous and homozygous, and 1038A > G heterozygous in exon 8) in 22 out of 70 patients studied. In conclusion, NPHS2 gene mutations are not a major cause of chronic renal insufficiency caused by late SRNS in Chinese southern infants. PMID- 25112472 TI - Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies. AB - Intervertebral disc degeneration (IDD) is a chronic, complex process associated with low back pain; mechanisms of its occurrence have not yet been fully elucidated. Its process is not only accompanied by morphological changes, but also by systematic changes in its histological and biochemical properties. Many cellular and molecular mechanisms have been reported to be related with IDD and to reverse degenerative trends, abnormal conditions of the living cells and altered cell phenotypes would need to be restored. Promising biological therapeutic strategies still rely on injection of active substances, gene therapy and cell transplantation. With advanced study of tissue engineering protocols based on cell therapy, combined use of seeding cells, bio-active substances and bio-compatible materials, are promising for IDD regeneration. Recently reported progenitor cells within discs themselves also hold prospects for future IDD studies. This article describes the background of IDD, current understanding and implications of potential therapeutic strategies. PMID- 25112469 TI - Clinical significance of HuR expression in human malignancy. AB - Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of target mRNAs. The aim of the present review was to summarize and present the currently available information in the English literature on HuR expression in various human tumors, verifying its possible clinical significance. HuR function is directly linked to its subcellular localization. In normal cells, HuR is mostly localized in the nucleus, while in malignant cells, an increase in cytoplasmic HuR levels has been noted, in both cell lines and tissue samples. Moreover, in malignancy, elevated HuR expression levels and cytoplasmic immunohistochemical pattern have been correlated with advanced clinicopathological parameters and altered expression levels of proteins implicated in neoplasia. Additionally, elevated HuR expression levels and mainly cytoplasmic immunohistochemical pattern were correlated with decreased patients' survival rate in various human tumors. HuR is a putative drug target for cancer therapy, since it is expressed ubiquitously in malignant clinical samples and has an apparently consistent role in tumor formation and progression. PMID- 25112473 TI - Towards an informative mutant phenotype for every bacterial gene. AB - Mutant phenotypes provide strong clues to the functions of the underlying genes and could allow annotation of the millions of sequenced yet uncharacterized bacterial genes. However, it is not known how many genes have a phenotype under laboratory conditions, how many phenotypes are biologically interpretable for predicting gene function, and what experimental conditions are optimal to maximize the number of genes with a phenotype. To address these issues, we measured the mutant fitness of 1,586 genes of the ethanol-producing bacterium Zymomonas mobilis ZM4 across 492 diverse experiments and found statistically significant phenotypes for 89% of all assayed genes. Thus, in Z. mobilis, most genes have a functional consequence under laboratory conditions. We demonstrate that 41% of Z. mobilis genes have both a strong phenotype and a similar fitness pattern (cofitness) to another gene, and are therefore good candidates for functional annotation using mutant fitness. Among 502 poorly characterized Z. mobilis genes, we identified a significant cofitness relationship for 174. For 57 of these genes without a specific functional annotation, we found additional evidence to support the biological significance of these gene-gene associations, and in 33 instances, we were able to predict specific physiological or biochemical roles for the poorly characterized genes. Last, we identified a set of 79 diverse mutant fitness experiments in Z. mobilis that are nearly as biologically informative as the entire set of 492 experiments. Therefore, our work provides a blueprint for the functional annotation of diverse bacteria using mutant fitness. PMID- 25112474 TI - Epoxide-mediated differential packaging of Cif and other virulence factors into outer membrane vesicles. AB - Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a number of secreted bacterial proteins, including phospholipases, alkaline phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide hydrolase, was shown to be regulated at the transcriptional level by epoxides, which serve as ligands of the repressor, CifR. Here, we tested whether epoxides have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in the presence of specific epoxides but not a hydrolysis product increased Cif packaging into OMVs in a CifR-independent fashion. The outer membrane protein, OprF, was also increased under these conditions, but alkaline phosphatase activity was not significantly altered. Additionally, we demonstrated that OMV shape and density were affected by epoxide treatment, with two distinct vesicle fractions present when cells were treated with epibromohydrin (EBH), a model epoxide. Vesicles isolated from the two density fractions exhibited different protein profiles in Western blotting and silver staining. We have shown that a variety of clinically or host-relevant treatments, including antibiotics, also alter the proteins packaged in OMVs. Proteomic analysis of purified OMVs followed by an analysis of transposon mutant OMVs yielded mutants with altered vesicle packaging. Finally, epithelial cell cytotoxicity was reduced in the vesicles formed in the presence of EBH, suggesting that this epoxide alters the function of the OMVs. Our data support a model whereby clinically or host-relevant signals mediate differential packaging of virulence factors in OMVs, which results in functional consequences for host-pathogen interactions. PMID- 25112475 TI - The disulfide bonding system suppresses CsgD-independent cellulose production in Escherichia coli. AB - The bacterial extracellular matrix encases cells and protects them from host related and environmental insults. The Escherichia coli master biofilm regulator CsgD is required for the production of the matrix components curli and cellulose. CsgD activates the diguanylate cyclase AdrA, which in turn stimulates cellulose production through cyclic di-GMP (c-di-GMP). Here, we identified and characterized a CsgD- and AdrA-independent cellulose production pathway that was maximally active when cultures were grown under reducing conditions or when the disulfide bonding system (DSB) was compromised. The CsgD-independent cellulose activation pathway was dependent on a second diguanylate cyclase, called YfiN. c di-GMP production by YfiN was repressed by the periplasmic protein YfiR, and deletion of yfiR promoted CsgD-independent cellulose production. Conversely, when YfiR was overexpressed, cellulose production was decreased. Finally, we found that YfiR was oxidized by DsbA and that intraprotein YfiR disulfide bonds stabilized YfiR in the periplasm. Altogether, we showed that reducing conditions and mutations in the DSB system caused hyperactivation of YfiN and subsequent CsgD-independent cellulose production. PMID- 25112476 TI - Mutations in the primary sigma factor sigmaA and termination factor rho that reduce susceptibility to cell wall antibiotics. AB - Combinations of glycopeptides and beta-lactams exert synergistic antibacterial activity, but the evolutionary mechanisms driving resistance to both antibiotics remain largely unexplored. By repeated subculturing with increasing vancomycin (VAN) and cefuroxime (CEF) concentrations, we isolated an evolved strain of the model bacterium Bacillus subtilis with reduced susceptibility to both antibiotics. Whole-genome sequencing revealed point mutations in genes encoding the major sigma factor of RNA polymerase (sigA), a cell shape-determining protein (mreB), and the rho termination factor (rho). Genetic-reconstruction experiments demonstrated that the G-to-C substitution at position 336 encoded by sigA (sigA(G336C)), in the domain that recognizes the -35 promoter region, is sufficient to reduce susceptibility to VAN and works cooperatively with the rho(G56C) substitution to increase CEF resistance. Transcriptome analyses revealed that the sigA(G336C) substitution has wide-ranging effects, including elevated expression of the general stress sigma factor (sigma(B)) regulon, which is required for CEF resistance, and decreased expression of the glpTQ genes, which leads to fosfomycin (FOS) resistance. Our findings suggest that mutations in the core transcriptional machinery may facilitate the evolution of resistance to multiple cell wall antibiotics. PMID- 25112478 TI - Enzymes involved in a novel anaerobic cyclohexane carboxylic acid degradation pathway. AB - The anaerobic degradation of cyclohexane carboxylic acid (CHC) has so far been studied only in Rhodopseudomonas palustris, in which CHC is activated to cyclohexanoyl coenzyme A (cyclohexanoyl-CoA [CHCoA]) and then dehydrogenated to cyclohex-1-ene-1-carboxyl-CoA (CHeneCoA). This intermediate is further degraded by reactions of the R. palustris-specific benzoyl-CoA degradation pathway of aromatic compounds. However, CHeneCoA is not an intermediate in the degradation of aromatic compounds in all other known anaerobic bacteria; consequently, degradation of CHC was mostly unknown in anaerobic bacteria. We identified a previously unknown CHC degradation pathway in the Fe(III)-reducing Geobacter metallireducens by determining the following CHC-induced in vitro activities: (i) the activation of CHC to CHCoA by a succinyl-CoA:CHC CoA transferase, (ii) the 1,2-dehydrogenation of CHCoA to CHeneCoA by CHCoA dehydrogenase, and (iii) the unusual 1,4-dehydrogenation of CHeneCoA to cyclohex-1,5-diene-1-carboxyl-CoA. This last represents a previously unknown joint intermediate of the CHC and aromatic compound degradation pathway in bacteria other than R. palustris. The enzymes catalyzing the three reactions were purified and characterized as specific enzymes after heterologous expression of the encoding genes. Quantitative reverse transcription-PCR revealed that expression of these genes was highly induced during growth with CHC but not with benzoate. The newly identified CHC degradation pathway is suggested to be present in nearly all CHC degrading anaerobic bacteria, including denitrifying, Fe(III)-reducing, sulfate reducing, and fermenting bacteria. Remarkably, all three CHC degradation pathways always link CHC catabolism to the catabolic pathways of aromatic compounds. We propose that the capacity to use CHC as a carbon source evolved from already existing aromatic compound degradation pathways. PMID- 25112479 TI - Competence for genetic transformation in Streptococcus pneumoniae: mutations in sigmaA bypass the comW requirement. AB - Competence for genetic transformation in the genus Streptococcus depends on an alternative sigma factor, sigma(X), for coordinated synthesis of 23 proteins, which together establish the X state by permitting lysis of incompetent streptococci, uptake of DNA fragments, and integration of strands of that DNA into the resident genome. Initiation of transient accumulation of high levels of sigma(X) is coordinated between cells by transcription factors linked to peptide pheromone signals. In Streptococcus pneumoniae, elevated sigma(X) is insufficient for development of full competence without coexpression of a second competence specific protein, ComW. ComW, shared by eight species in the Streptococcus mitis and Streptococcus anginosus groups, is regulated by the same pheromone circuit that controls sigma(X), but its role in expression of the sigma(X) regulon is unknown. Using the strong, but not absolute, dependence of transformation on comW as a selective tool, we collected 27 independent comW bypass mutations and mapped them to 10 single-base transitions, all within rpoD, encoding the primary sigma factor subunit of RNA polymerase, sigma(A). Eight mapped to sites in rpoD region 4 that are implicated in interaction with the core beta subunit, indicating that ComW may act to facilitate competition of the alternative sigma factor sigma(X) for access to core polymerase. PMID- 25112477 TI - Serotype-converting bacteriophage SfII encodes an acyltransferase protein that mediates 6-O-acetylation of GlcNAc in Shigella flexneri O-antigens, conferring on the host a novel O-antigen epitope. AB - Shigella flexneri O-antigen is an important and highly variable cell component presented on the outer leaflet of the outer membrane. Most Shigella flexneri bacteria share an O-antigen backbone composed of ->2)-alpha-L-Rhap(III)-(1->2) alpha-L-Rhap(II)-(1->3)-alpha-L-Rhap(I)-(1->3)-beta-D-GlcpNAc-(1-> repeats, which can be modified by adding various chemical groups to different sugars, giving rise to diverse O-antigen structures and, correspondingly, to various serotypes. The known modifications include glucosylation on various sugar residues, O acetylation on Rha(I) or/and Rha(III), and phosphorylation with phosphoethanolamine on Rha(II) or/and Rha(III). Recently, a new O-antigen modification, namely, O-acetylation at position 6 of N-acetylglucosamine (GlcNAc), has been identified in S. flexneri serotypes 2a, 3a, Y, and Yv. In this study, the genetic basis of the 6-O-acetylation of GlcNAc in S. flexneri was elucidated. An O-acyltransferase gene designated oacD was found to be responsible for this modification. The oacD gene is carried on serotype-converting bacteriophage SfII, which is integrated into the host chromosome by lysogeny to form a prophage responsible for the evolvement of serotype 2 of S. flexneri. The OacD-mediated 6-O-acetylation also occurs in some other S. flexneri serotypes that carry a cryptic SfII prophage with a dysfunctional gtr locus for type II glucosylation. The 6-O-acetylation on GlcNAc confers to the host a novel O antigen epitope, provisionally named O-factor 10. These findings enhance our understanding of the mechanisms of the O-antigen variation and enable further studies to understand the contribution of the O-acetylation to the antigenicity and pathogenicity of S. flexneri. PMID- 25112480 TI - Functional and structural analysis of HicA3-HicB3, a novel toxin-antitoxin system of Yersinia pestis. AB - The mechanisms involved in the virulence of Yersinia pestis, the plague pathogen, are not fully understood. In previous research, we found that a Y. pestis mutant lacking the HicB3 (YPO3369) putative orphan antitoxin was attenuated for virulence in a murine model of bubonic plague. Toxin-antitoxin systems (TASs) are widespread in prokaryotes. Most bacterial species possess many TASs of several types. In type II TASs, the toxin protein is bound and neutralized by its cognate antitoxin protein in the cytoplasm. Here we identify the hicA3 gene encoding the toxin neutralized by HicB3 and show that HicA3-HicB3 constitutes a new functional type II TAS in Y. pestis. Using biochemical and mutagenesis-based approaches, we demonstrate that the HicA3 toxin is an RNase with a catalytic histidine residue. HicB3 has two functions: it sequesters and neutralizes HicA3 by blocking its active site, and it represses transcription of the hicA3B3 operon. Gel shift assays and reporter fusion experiments indicate that the HicB3 antitoxin binds to two operators in the hicA3B3 promoter region. We solved the X-ray structures of HicB3 and the HicA3-HicB3 complex; thus, we present the first crystal structure of a TA complex from the HicAB family. HicB3 forms a tetramer that can bind two HicA3 toxin molecules. HicA3 is monomeric and folds as a double-stranded-RNA binding domain. The HicB3 N-terminal domain occludes the HicA3 active site, whereas its C-terminal domain folds as a ribbon-helix-helix DNA-binding motif. PMID- 25112483 TI - 3,6-Epidioxy-1,10-bisaboladiene inhibits G1 -specific transcription through Swi4/Swi6 and Mbp1/Swi6 via the Hog1 stress pathway in yeast. AB - 3,6-Epidioxy-1,10-bisaboladiene (EDBD), a bisabolane sesquiterpene endoperoxide compound, was previously isolated from Cacalia delphiniifolia and C. hastata in northern Japan. EDBD has cytotoxic effects and induces apoptosis via phosphorylation of p38 mitogen-activated protein kinase in human promyelocytic leukemia HL60 cells. However, the mechanism of action of EDBD has not yet been fully elucidated. In this study, we examined the molecular mechanisms of EDBD in the budding yeast Saccharomyces cerevisiae. EDBD arrested the growth of S. cerevisiae cells by suppressing progression from the G1 phase to the S phase and from the G2 phase to the M phase. Moreover, biochemical and genetic analyses revealed that EDBD activated environmental stress-response pathways involving Hog1 and affected Cln3/G1 cyclin activity, thereby inhibiting the expression of SCB-binding factor and MCB-binding factor target genes. Our results provided important insights into the functions of EDBD in tumor cells and may facilitate the development of EDBD-based antitumor therapies. STRUCTURED DIGITAL ABSTRACT: *Swi4 physically interacts with Swi6 by anti tag coimmunoprecipitation (View interaction). PMID- 25112484 TI - The association between vibration and vascular injury in rheumatic diseases: a review of the literature. AB - Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynaud's phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of "vascular", "neural" and "intravascular". Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account. PMID- 25112481 TI - A comparison of the effectiveness of physical activity and sedentary behaviour interventions in reducing sedentary time in adults: a systematic review and meta analysis of controlled trials. AB - The objective of this study was to systematically review the literature and compare the effectiveness of controlled interventions with a focus on physical activity (PA) and/or sedentary behaviours (SBs) for reducing sedentary time in adults. Six electronic databases were searched to identify all studies that examined the effects of interventions that targeted PA and/or SBs and that reported on changes in SBs (sedentary, sitting or television time). A qualitative synthesis was performed for all studies, and meta-analyses conducted among studies with mean differences (min/d) of sedentary time. PROSPERO: CRD42014006535. Sixty-five controlled studies met inclusion criteria; 33 were used in the meta-analyses. Interventions with a focus on PA or that included a PA and SB component produced less consistent findings and generally resulted in modest reductions in sedentary time (PA: standardized mean differences [SMD] = 0.22 [95% confidence interval {CI}: -0.35, -0.10], PA+SB: SMD= -0.37 [95% CI: 0.69, -0.05]). Moderate quality evidence from the randomized controlled trial meta-analysis coupled with the qualitative synthesis provides consistent evidence that large and clinically meaningful reductions in sedentary time can be expected from interventions with a focus on reducing SBs (SMD= -1.28 [95% CI: -1.68, 0.87] ). There is evidence to support the need for interventions to include a component focused on reducing SBs in order to generate clinically meaningful reductions in sedentary time. PMID- 25112485 TI - The relationship between daily urinary sodium excretion and metabolic syndrome in patients with kidney transplantation. AB - BACKGROUND: The aim of this study was to determine whether there is a relationship between daily urinary sodium excretion and metabolic syndrome in kidney transplantation patients. MATERIAL AND METHODS: This cross-sectional study included 76 adult renal transplantation recipients. To calculate urinary sodium excretion, 24-h urine samples were collected. Metabolic syndrome was diagnosed according to Adult Treatment Panel III (ATP III) criteria updated in a statement from the American Heart Association (AHA)/National Heart, Lung, and Blood Institute (NHLBI) in 2005. RESULTS: Mean age of the 76 patients was 38 +/- 10 years; 21 of the 76 patients were female. Metabolic syndrome was found in 52 (68.4%) of the 76 renal transplantation patients. Mean daily urinary sodium excretion was 190 +/- 102 mmol/day, which is equal to a salt intake of 11.1 g/day. Daily urinary sodium excretion was significantly higher in patients with metabolic syndrome compared to those without metabolic syndrome (209 +/- 112 mmol/day and 150 +/- 62 mmol/day, respectively, p: 0.005). Daily urinary sodium excretion correlated with diastolic blood pressure (r: 0.254, p: 0.028), serum glucose concentration (r: 0.446, p: <0.001), and creatinine clearance (r: 478, p: <0.001). In addition, although there was no significant correlation between daily urinary sodium excretion and systolic blood pressure, the statistical significance was borderline (r: 0.221, p: 0.056). CONCLUSIONS: There is a significant relationship between daily urinary sodium excretion and metabolic syndrome in renal transplant recipients. The Turkish kidney transplantation patients consume a great amount of salt and salt intake is positively correlated with blood pressure. PMID- 25112486 TI - Factors Associated With Hospitalizations Among HIV-Infected Adults in the United States: Review of the Literature. AB - Although improving health outcomes in human immunodeficiency virus (HIV)-infected persons has been identified as a national priority, little is known about the factors associated with hospitalizations of HIV-infected persons in the highly active antiretroviral therapy (HAART) era. Since the introduction of HAART in 1996, there has been a dramatic increase in the life expectancy of HIV-infected persons. However, aging and the long term use of HIV medications have led to an increased incidence of chronic, non-HIV-related illnesses. To improve patient outcomes, the factors that contribute to co-morbidities in HIV-infected persons need to be identified. As a first step, we will summarize the current literature on causes and contributing factors of hospitalizations in adults infected with HIV in the HAART era. PMID- 25112487 TI - Noninvasive prenatal testing. AB - Noninvasive prenatal testing (NIPT) refers to recently developed genetic tests of the maternal serum that allow higher detection rates of trisomy 21 and other chromosomal aneuploidies in high-risk pregnancies. Noninvasive prenatal test analyzes cell-free DNA (cfDNA) in the maternal serum. Approximately 3% to 15% of cfDNA in the maternal blood is of fetal origin. Analysis of cfDNA can help identify fetuses affected with trisomy 21 and several other fetal aneuploidies. Testing can be performed after 9 to 10 weeks' gestation and has a higher sensitivity and specificity for trisomy 21 than other aneuploidy screening test. Noninvasive prenatal test has been studied and validated in singleton pregnancies at risk for trisomy 21 secondary to advanced maternal age, an abnormal serum screen, personal or family history of aneuploidy, or abnormal ultrasound findings, if these are suggestive of trisomy 13, 18, or 21. The utilization of NIPT for genetic screening has increased rapidly since introduction of the first clinical test in October 2011. Currently, there are limitations to NIPT including the possibility of test failure (2.6%-5.4%) and the focus on only the common trisomies. Noninvasive prenatal test is a screening test, and both false-positive (0.2%-1%) and false-negative results can occur. As the technology for NIPT is further evaluated, this test is likely to be increasingly used for prenatal screening. This review provides the obstetric clinician with an update of the current issues concerning NIPT. PMID- 25112488 TI - The impact of preoperative gonadotropin-releasing hormone agonist treatment on women with uterine fibroids: a meta-analysis. AB - AIM: The objectives of this study were to evaluate the efficacy of gonadotropin releasing hormone agonist (GnRHa) treatment before surgery for women with uterine fibroids and to explore potential factors predicting the pooled effect sizes. METHODS: A meta-analysis was performed from published randomized controlled trials using the random effects model. The efficacy of preoperative treatment with GnRHa was investigated according to volume measurements of fibroid tumors, postoperative complications, myoma recurrence, and changes in fertility. Metaregression and subgroup analysis were used to identify potential predictors of the effect sizes. RESULTS: A total of 26 studies were selected for the meta analysis. Preoperative GnRHa therapy for women with uterine fibroids was associated with a smaller preoperative volume of fibroid tumors, increased hemoglobin and hematocrit levels, reductions in preoperative pelvic symptoms and the vertical incision rate, and a higher proportion of patients undergoing a vaginal procedure. No differences were observed in postoperative complications, myoma recurrence, and changes in fertility in the GnRHa-treated patients compared with patients treated with placebo or alternative clinical agents. The metaregression suggested that age, the duration of GnRHa treatment, the type of control group, and the type of surgery were important predictors of the efficacy of preoperative GnRHa treatment. CONCLUSIONS: Preoperative GnRHa treatment for women with uterine fibroids reduces preoperative fibroid size and increases hemoglobin and hematocrit levels. Gonadotropin-releasing hormone agonist pretreatment reduces preoperative pelvic symptoms and the rate of vertical incision and results in a higher chance of patients to receive a vaginal procedure, without significant difference in postoperative complications when comparing with other preoperative treatments. The patients' age, duration of GnRHa treatment, agents selected as control, and types of surgical procedures serve as predictors of the efficacy of preoperative GnRHa treatment. PMID- 25112489 TI - Definition and epidemiology of unexplained infertility. AB - The diagnosis of unexplained infertility can be made only after excluding common causes of infertility using standard fertility investigations,which include semen analysis, assessment of ovulation, and tubal patency test. These tests have been selected as they have definitive correlation with pregnancy. It is estimated that a standard fertility evaluation will fail to identify an abnormality in approximately 15% to 30% of infertile couples. The reported incidence of such unexplained infertility varies according to the age and selection criteria in the study population. We conducted a review of the literature via MEDLINE. Articles were limited to English-language, human studies published between 1950 and 2013. Since first coined more than 50 years ago, the term unexplained infertility has been a subject of debate. Although additional investigations are reported to explain or define other causes of infertility, these have high false-positive results and therefore cannot be recommended for routine clinical practice. Couples with unexplained infertility might be reassured that even after 12 months of unsuccessful attempts, 50% will conceive in the following 12 months and another 12% in the year after. PMID- 25112491 TI - Shear stress and VEGF enhance endothelial differentiation of human adipose derived stem cells. AB - Herein we combine chemical and mechanical stimulation to investigate the effects of vascular endothelial growth factor (VEGF) and physiological shear stress in promoting the differentiation human adipose derived stem cells (ADSCs) into endothelial cells. ADSCs were isolated and characterized; endothelial differentiation was promoted by culturing confluent cells in 50 ng/ml VEGF under physiological shear stress for up to 14 days. Afterwards, endothelial cells were seeded onto collagen or acellular aortic valve matrices and exposed to four culture conditions: shear stress + VEGF; shear stress - VEGF; static + VEGF and static - VEGF. After 7 days, phenotype was investigated. ADSCs subjected to shear stress and VEGF express a comprehensive range of specific endothelial markers (vWF, eNOS and FLT-1 after 7 days and CD31, FLk-1 and VE-cadherin after 14 days) and maintain the phenotype when seeded onto scaffolds. Our protocol proved to be an efficient source of endothelial-like cells for tissue engineering based on autologous ADSC. PMID- 25112492 TI - Identifying determinants of care for tailoring implementation in chronic diseases: an evaluation of different methods. AB - BACKGROUND: The tailoring of implementation interventions includes the identification of the determinants of, or barriers to, healthcare practice. Different methods for identifying determinants have been used in implementation projects, but which methods are most appropriate to use is unknown. METHODS: The study was undertaken in five European countries, recommendations for a different chronic condition being addressed in each country: Germany (polypharmacy in multimorbid patients); the Netherlands (cardiovascular risk management); Norway (depression in the elderly); Poland (chronic obstructive pulmonary disease- COPD); and the United Kingdom (UK) (obesity). Using samples of professionals and patients in each country, three methods were compared directly: brainstorming amongst health professionals, interviews of health professionals, and interviews of patients. The additional value of discussion structured through reference to a checklist of determinants in addition to brainstorming, and determinants identified by open questions in a questionnaire survey, were investigated separately. The questionnaire, which included closed questions derived from a checklist of determinants, was administered to samples of health professionals in each country. Determinants were classified according to whether it was likely that they would inform the design of an implementation intervention (defined as plausibly important determinants). RESULTS: A total of 601 determinants judged to be plausibly important were identified. An additional 609 determinants were judged to be unlikely to inform an implementation intervention, and were classified as not plausibly important. Brainstorming identified 194 of the plausibly important determinants, health professional interviews 152, patient interviews 63, and open questions 48. Structured group discussion identified 144 plausibly important determinants in addition to those already identified by brainstorming. CONCLUSIONS: Systematic methods can lead to the identification of large numbers of determinants. Tailoring will usually include a process to decide, from all the determinants that are identified, those to be addressed by implementation interventions. There is no best buy of methods to identify determinants, and a combination should be used, depending on the topic and setting. Brainstorming is a simple, low cost method that could be relevant to many tailored implementation projects. PMID- 25112493 TI - Vitamin D insufficiency and abnormal hemoglobin a1c in black and white older persons. AB - BACKGROUND: Although vitamin D has been mechanistically linked to insulin secretion and sensitivity, it remains unclear whether low 25-hydroxyvitamin D levels confer an increased risk of impaired glucose metabolism. We evaluated the relationship between vitamin D insufficiency (25-hydroxyvitamin D < 20ng/mL) and abnormal hemoglobin A1c (A1c) (>=6.5%) in community-dwelling older persons and examined whether this relationship differed according to race. METHODS: Participants were 2,193 persons of age 70-79 years at Year 1 (52% women; 37% black) in the Health, Aging, and Body Composition study who had clinic visits at Years 2 and 4. Logistic regression analyses, adjusted for potential confounders, were used to evaluate the association between vitamin D insufficiency and abnormal A1c 2 years later. Interaction of race and vitamin D insufficiency was tested. RESULTS: A total of 665 (30%) and 301 (14%) of the participants had vitamin D insufficiency at Year 2 and abnormal A1c at Year 4, respectively. After controlling for demographics, other potential confounders, and diabetes status at Year 4 (n = 477 diabetics), we found that vitamin D insufficiency was associated with an increased likelihood of having abnormal A1c (odds ratio = 1.56; 95% CI: 1.03-2.37). We also found that this relationship persisted among the 1,765 participants without diabetes in Year 2 (odds ratio = 2.33; 95% CI: 1.00-5.40). Findings did not differ by race. CONCLUSIONS: Vitamin D insufficiency was associated with abnormal A1c levels among black and white older persons independent of diabetes status. Future studies are needed to establish the temporal relationship between vitamin D and A1c in diverse samples of older persons. PMID- 25112495 TI - The assessment of general well-being using spontaneous burrowing behaviour in a short-term model of chemotherapy-induced mucositis in the rat. AB - Mucositis is a common and serious side-effect experienced by cancer patients during treatment with chemotherapeutic agents. Consequently, programmes of research focus on the elucidation of novel therapeutics for alleviation of mucositis symptoms, and these frequently use animal models. However, although these models are assumed to be painful and distressing to the animal, endpoints are difficult to determine. The aim of this study was to evaluate whether a change in burrowing behaviour could provide an indication of disease onset and potentially be applied as a humane endpoint. Baseline burrowing behaviour was measured in healthy animals on three occasions by determining the weight of gravel displaced from a hollow tube. Mucositis was then induced in the same animals by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and burrowing behaviour recorded over three consecutive days. Standard measures of disease progression, including body weight loss and clinical score, were also made. The presence of mucositis was confirmed at necropsy by findings of decreased duodenal and colon lengths, and reduced liver, spleen and thymus weights in comparison with non-treated control animals. Histological score of the jejunum and ileum was also significantly increased. Mucositis onset coincided with a decrease in mean burrowing behaviour which was progressive, however this result did not achieve statistical significance (P = 0.66).We conclude that burrowing may be a useful indicator of inflammation in the mucositis model, although this requires further characterization. Pre-selection of animals into treatment groups based on their prior burrowing performance should be pursued in further studies. PMID- 25112496 TI - Alkaline phosphatases in microbialites and bacterioplankton from Alchichica soda lake, Mexico. AB - Dissolved organic phosphorus utilization by different members of natural communities has been closely linked to microbial alkaline phosphatases whose affiliation and diversity is largely unknown. Here we assessed genetic diversity of bacterial alkaline phosphatases phoX and phoD, using highly diverse microbial consortia (microbialites and bacterioplankton) as study models. These microbial consortia are found in an oligo-mesotrophic soda lake with a particular geochemistry, exhibiting a low calcium concentration and a high Mg : Ca ratio relative to seawater. In spite of the relative low calcium concentration in the studied system, our results highlight the diversity of calcium-based metallophosphatases phoX and phoD-like in heterotrophic bacteria of microbialites and bacterioplankton, where phoX was the most abundant alkaline phosphatase found. phoX and phoD-like phylotypes were more numerous in microbialites than in bacterioplankton. A larger potential community for DOP utilization in microbialites was consistent with the TN : TP ratio, suggesting P limitation within these assemblages. A cross-system comparison indicated that diversity of phoX in Lake Alchichica was similar to that of other aquatic systems with a naturally contrasting ionic composition and trophic state, although no phylotypes were shared among systems. PMID- 25112494 TI - Enhanced somatosensory feedback reduces prefrontal cortical activity during walking in older adults. AB - BACKGROUND: The coordination of steady state walking is relatively automatic in healthy humans, such that active attention to the details of task execution and performance (controlled processing) is low. Somatosensation is a crucial input to the spinal and brainstem circuits that facilitate this automaticity. Impaired somatosensation in older adults may reduce automaticity and increase controlled processing, thereby contributing to deficits in walking function. The primary objective of this study was to determine if enhancing somatosensory feedback can reduce controlled processing during walking, as assessed by prefrontal cortical activation. METHODS: Fourteen older adults (age 77.1+/-5.56 years) with mild mobility deficits and mild somatosensory deficits participated in this study. Functional near-infrared spectroscopy was used to quantify metabolic activity (tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and gait spatiotemporal data were measured during treadmill walking and overground walking while participants wore normal shoes and under two conditions of enhanced somatosensation: wearing textured insoles and no shoes. RESULTS: Relative to walking with normal shoes, textured insoles yielded a bilateral reduction of prefrontal cortical activity for treadmill walking (DeltaTOI = -0.85 and -1.19 for left and right hemispheres, respectively) and for overground walking (DeltaTOI = -0.51 and -0.66 for left and right hemispheres, respectively). Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical activity for treadmill walking (DeltaTOI = -0.69 and -1.13 for left and right hemispheres, respectively), but not overground walking. CONCLUSIONS: Enhanced somatosensation reduces prefrontal activity during walking in older adults. This suggests a less intensive utilization of controlled processing during walking. PMID- 25112498 TI - Bloom of the cyanobacterium Moorea bouillonii on the gorgonian coral Annella reticulata in Japan. AB - Coral populations are in decline due to environmental changes and biological attacks by predators and infectious diseases. Here, we report a localized bloom of the benthic filamentous cyanobacterium Moorea bouillonii (formerly Lyngbya bouillonii) observed exclusively on the gorgonian (sea fan) coral Annella reticulata at around 20 m depth in Japan. The degree of infection has reached 26% among different sizes of Annella colonies. Thick and continuous growth of Moorea may be sustained partly by symbiotic alpheid shrimp, which affix Moorea filaments to gorgonian corals for use as food and shelter. Most filaments get entangled on the coral colony, some penetrate into the stem of the coral with a swollen end like a root hair, which appears to function as an anchor in Annella. In addition to the cyanobacterium-shrimp interaction, the new trait of anchoring by the cyanobacterium into gorgonian coral may contribute to persistence of this bloom. PMID- 25112497 TI - Perceptions of, attitudes towards and barriers to male involvement in newborn care in rural Ghana, West Africa: a qualitative analysis. AB - BACKGROUND: Male involvement in various health practices is recognized as an important factor in improving maternal and child health outcomes. Male involvement interventions involve men in a variety of ways, at varying levels of inclusion and use a range of outcome measures. There is little agreement on how male involvement should be measured and some authors contend that male involvement may actually be detrimental to women's empowerment and autonomy. Few studies explore the realities, perceptions, determinants and efficacy of male involvement in newborn care, especially in African contexts. METHODS: Birth narratives of recent mothers (n = 25), in-depth interviews with recent fathers (n = 12) and two focus group discussions with fathers (n = 22) were conducted during the formative research phase of a community-based newborn care trial. Secondary analysis of this qualitative data identified emergent themes and established overall associations related to male involvement, newborn care and household roles in a rural African setting. RESULTS: Data revealed that gender dictates many of the perceptions and politics surrounding newborn care in this context. The influence of mother-in-laws and generational power dynamics were also identified as significant. Women alone perform almost all tasks related to newborn care whereas men take on the traditional responsibilities of economic providers and decision makers, especially concerning their wives' and children's health. Most men were interested in being more involved in newborn care but identified barriers to increased involvement, many of which related to gendered and generational divisions of labour and space. CONCLUSIONS: Men defined involvement in a variety of ways, even if they were not physically involved in carrying out newborn care tasks. Some participant comments revealed potential risks of increasing male involvement suggesting that male involvement alone should not be an outcome in future interventions. Rather, the effect of male involvement on women's autonomy, the dynamics of senior women's influence and power and the real impact on health outcomes should be considered in intervention design and implementation. Any male involvement intervention should integrate a detailed understanding of context and strategies to include men in maternal and child health should be mutually empowering for both women and men. PMID- 25112499 TI - Embryogenesis of Heliconius erato (Lepidoptera, Nymphalidae): a contribution to the anatomical development of an evo-devo model organism. AB - This study reports on the embryogenesis of Heliconius erato phyllis between blastoderm formation and the prehatching larval stage. Syncytial blastoderm formation occurred approximately 2 h after egg laying (AEL) and at about 4 h, the cellular blastoderm was formed. The germ band arose from the entire length of the blastoderm, and rapidly became compacted occupying approximately two-thirds of the egg length. At about 7 h AEL, protocephalon and protocorm differentiation occurred. Continued proliferation of the germ band was followed by penetration into the yolk mass, forming a C-shaped embryo at about 10 h. Approximately 12 h AEL, the gnathal, thoracic and abdominal segments became visible. The primordium of the mouthparts and thoracic legs formed as paired evaginations, while the prolegs formed as paired lobes. At about 30 h, the embryo reversed dorsoventrally. Approximately 32 h AEL, the protocephalon and gnathal segments fused, shifting the relative position of the rudimentary appendages in this region. At about 52 h, the embryo was U-shaped in lateral view and at approximately 56 h, the bristles began evagination from the larval cuticle. Larvae hatched at about 72 h. We found that H. erato phyllis followed an embryonic pattern consistent with long-germ embryogenesis. Thus, we believe that H. erato phyllis should be classified as a long-germ lepidopteran. The study of H. erato phyllis embryogenesis provided a structural glimpse into the morphogenetic events that occur in the Heliconius egg period. This study could help future molecular approaches to understanding the evolution of Heliconius development. PMID- 25112500 TI - Mobilization of patients on venovenous extracorporeal membrane oxygenation support using an ECMO helmet. PMID- 25112501 TI - The assessment of transpulmonary pressure in mechanically ventilated ARDS patients. AB - PURPOSE: The optimal method for estimating transpulmonary pressure (i.e. the fraction of the airway pressure transmitted to the lung) has not yet been established. METHODS: In this study on 44 patients with acute respiratory distress syndrome (ARDS), we computed the end-inspiratory transpulmonary pressure as the change in airway and esophageal pressure from end-inspiration to atmospheric pressure (i.e. release derived) and as the product of the end inspiratory airway pressure and the ratio of lung to respiratory system elastance (i.e. elastance derived). The end-expiratory transpulmonary pressure was estimated as the product of positive end-expiratory pressure (PEEP) minus the direct measurement of esophageal pressure and by the release method. RESULTS: The mean elastance- and release-derived transpulmonary pressure were 14.4 +/- 3.7 and 14.4 +/- 3.8 cmH2O at 5 cmH2O of PEEP and 21.8 +/- 5.1 and 21.8 +/- 4.9 cmH2O at 15 cmH2O of PEEP, respectively (P = 0.32, P = 0.98, respectively), indicating that these parameters were significantly related (r(2) = 0.98, P < 0.001 at 5 cmH2O of PEEP; r(2) = 0.93, P < 0.001 at 15 cmH2O of PEEP). The percentage error was 5.6 and 12.0 %, respectively. The mean directly measured and release-derived transpulmonary pressure were -8.0 +/- 3.8 and 3.9 +/- 0.9 cmH2O at 5 cmH2O of PEEP and -1.2 +/- 3.2 and 10.6 +/- 2.2 cmH2O at 15 cmH2O of PEEP, respectively, indicating that these parameters were not related (r(2) = 0.07, P = 0.08 at 5 cmH2O of PEEP; r (2) = 0.10, P = 0.53 at 15 cmH2O of PEEP). CONCLUSIONS: Based on our observations, elastance-derived transpulmonary pressure can be considered to be an adequate surrogate of the release-derived transpulmonary pressure, while the release-derived and directly measured end-expiratory transpulmonary pressure are not related. PMID- 25112502 TI - Myocardial viability in human septic heart. PMID- 25112503 TI - Extracorporeal membrane oxygenation as a bridge to allogeneic T-cell depleted hematopoietic stem cell transplantation in infants with severe combined immune deficiency: is it feasible? PMID- 25112505 TI - Assessment of arsenic availability in soils using the diffusive gradients in thin films (DGT) technique--a comparison study of DGT and classic extraction methods. AB - This study was conducted to evaluate the feasibility and accuracy of available arsenic (As) measurement in soils using the diffusive gradients in thin films (DGT) technique and to shed further light on the risk evaluation of As contaminated soils. A bio-indicator method was used to evaluate the dependence of As concentrations in plant tissues (edible rape) on the As concentrations measured by other methods. DGT, extraction of soil pore water, 0.5 M NaHCO3, 1 M HCl, 1 M NH4Cl, 0.5 M NH4F, 0.1 M NaOH and 0.25 M H2SO4 extraction methods, as well as total As content in the soil were employed in this study. Edible rape was grown in 43 soils containing different concentrations of As. A better correlation was obtained between the As concentrations in plant tissues and the As concentrations measured by DGT than between plant concentrations and those measured by other methods. The coefficients of determination (R(2)) before and after growth of edible rape were 0.84 and 0.83, respectively. Levels of As in plants and in soil pore water were also closely related: the coefficients of determination (R(2)) between these variables before and after growth of edible rape were 0.83 and 0.81, respectively. Measurements from the chemical extraction methods were inferior to those from DGT and soil pore water. Levels of As in plants were more scattered and nonlinear with respect to total soil As content (R(2) = 0.27). The As measured by DGT closely reflected the pool of plant adsorbed As. From the data obtained in this study, we can conclude that DGT is an effective technique for the prediction and assessment of As bioavailability in soils. PMID- 25112504 TI - Bacteriophage as effective decolonising agent for elimination of MRSA from anterior nares of BALB/c mice. AB - BACKGROUND: Nasal carriers not only pose serious threat to themselves but also to the community by playing an active role in the dissemination of serious and life threatening S. aureus especially MRSA strains. The present study focuses on the use of broad spectrum lytic phage as decolonising agent. In addition, the combined use of lytic phage with mupirocin has also been investigated as an effective decolonising regimen. The effect of phage on the adherence, invasion and cytotoxic effect of MRSA strains on nasal epithelial cells was studied in an ex-vivo model of cultured murine nasal epithelial cells. This was followed by demonstration of therapeutic potential of phage along with mupirocin in decolonising the nares of BALB/c mice using a nasal model of MRSA colonisation. RESULTS: Phage was able to significantly reduce the in vitro adherence, invasion and cytotoxicity of MRSA 43300 as well as other clinical MRSA strains on murine nasal epithelial cells as compared to untreated control. Also, the frequency of emergence of spontaneous mutants decreased to negligible levels when both the agents (phage and mupirocin) were used together. CONCLUSION: Phage MR-10, given along with mupirocin showed an additive effect and the combination was able to effectively eradicate the colonising MRSA population from the nares of mice by day 5. PMID- 25112506 TI - Photodynamic inactivation of bacterial and yeast biofilms with a cationic porphyrin. AB - The efficiency of 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra iodide (Tetra-Py(+)-Me) in the photodynamic inactivation of single-species biofilms of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans and mixed biofilms of S. aureus and C. albicans was evaluated. The effect on the extracellular matrix of P. aeruginosa was also assessed. Irradiation with white light up to an energy dose of 64.8 J cm(-2) in the presence of 20 MUm of Tetra Py(+)-Me caused significant inactivation in all single-species biofilms (3-6 log reductions), although the susceptibility was attenuated in relation to planktonic cells. In mixed biofilms, the inactivation of S. aureus was as efficient as in single-species biofilms but the susceptibility of C. albicans decreased. In P. aeruginosa biofilms, a reduction of 81% in the polysaccharide content of the matrix was observed after treatment with a 20 MUm PS concentration and a total light dose of 64.8 J cm(-2). The results show that the Tetra-Py(+)-Me causes significant inactivation of the microorganisms, either in biofilms or in the planktonic form, and demonstrate that polysaccharides of the biofilm matrix may be a primary target of photodynamic damage. PMID- 25112507 TI - Motor neuron disease: Evaluation of ALS via transcranial magnetic stimulation. PMID- 25112511 TI - Neuro-oncology: Under-recognized mental incapacity in brain tumour patients. AB - Many patients with brain tumours possess inadequate mental capacity to provide informed consent, but this situation often goes undetected because clinicians do not routinely conduct formal cognitive assessments. This oversight should be recognized and rectified to enable optimum ethical and medical care of these vulnerable individuals. PMID- 25112510 TI - Epilepsy: Beyond the single nucleotide variant in epilepsy genetics. AB - Copy number variants (CNVs; deletions or duplications of chromosomal regions) have emerged as an important cause of human disease. In a recent study, epilepsy could be attributed to a pathogenic CNV in 5% of patients, but understanding the implications of a CNV for an individual patient can be challenging. PMID- 25112509 TI - The link between multiple sclerosis and depression. AB - Depression--be it a formal diagnosis based on consensus clinical criteria, or a collection of symptoms revealed by a self-report rating scale--is common in patients with multiple sclerosis (MS) and adds substantially to the morbidity and mortality associated with this disease. This Review discusses the prevalence and epidemiology of depression in patients with MS, before covering aetiological factors, including genetics, brain pathology, immunological changes, dysregulation of the hypothalamic-pituitary-adrenal axis, and psychosocial influences. Treatment options such as antidepressant drugs, cognitive-behavioural therapy, mindfulness-based therapy, exercise and electroconvulsive therapy are also reviewed in the context of MS-related depression. Frequent comorbid conditions, namely pain, fatigue, anxiety, cognitive dysfunction and alcohol use, are also summarized. The article then explores three key challenges facing researchers and clinicians: what is the optimal way to define depression in the context of diseases such as MS, in which the psychiatric and neurological symptoms overlap; how can current knowledge about the biological and psychological underpinnings of MS-related depression be used to boost the validity of this construct; and can intervention be made more effective through use of combination therapies with additive or synergistic effects, which might exceed the modest benefits derived from their individual components? PMID- 25112512 TI - Troponin elevations only detected with a high-sensitivity assay: clinical correlations and prognostic significance. AB - OBJECTIVES: With clinical use of high-sensitivity troponin I (hsTnI), more frequent troponin elevations will occur. However, the burden and implications of these elevations are not well understood. The authors quantified the prevalence of elevated hsTnI in patients presenting with possible acute coronary syndrome (ACS) who do not have elevated troponin with a current generation assay (cardiac troponin I [cTnI]) and determined the association of these newly detected elevations with a composite of all-cause mortality and subsequent cardiac hospitalization. METHODS: This was a prospective observational study of 808 subjects evaluated for possible ACS and followed for up to 1 year. Troponin values were measured with hsTnI (Abbott Laboratories) and cTnI (Abbott and Beckman Coulter). Cardiac hospitalization was defined as hospitalization for ACS, revascularization, acute heart failure (AHF), or tachy/brady arrhythmia that occurred after the index emergency department (ED) visit or hospital discharge. RESULTS: Forty subjects (5%) were diagnosed with ACS (26 myocardial infarction and 14 unstable angina). On the initial sample, the prevalence of elevated hsTnI among subjects with nonelevated cTnI was 9.2% using a gender-neutral cutoff (95% confidence interval [CI] = 7.1% to 11.4%) and 11.1% using a gender-specific cutoff (95% CI = 8.8% to 13.4%). Adjudicated diagnoses for subjects whose initial samples had elevated hsTnI but nonelevated cTnI (gender-neutral cutoff) were as follows: three (4.6%) ACS, 15 (23.1%) AHF, three (4.6%) volume overload etiology unclear/noncardiac, three (4.6%) cardiac (non-ACS), and 41 (63.1%) other. Of the 65 patients whose initial samples had hsTnI but nonelevated cTnI, eight developed cTnI elevation on subsequent serial sampling. After traditional cardiovascular risk factors and renal function were adjusted for, subjects with elevated initial hsTnI but nonelevated cTnI (initial and serial sampling) had a higher risk of all cause mortality and subsequent cardiac hospitalization than subjects with both nonelevated hsTnI and nonelevated cTnI (hazard ratio [HR] = 1.91, 95% CI = 1.14 to 3.19). CONCLUSIONS: On the initial sample, 9% to 11% of subjects without cTnI elevation had hsTnI elevation. Although the majority of the patients with these newly detected hsTnI elevations did not have ACS, they had a higher risk for all cause mortality and subsequent cardiac hospitalization. PMID- 25112508 TI - Treatment of neuromyelitis optica: state-of-the-art and emerging therapies. AB - Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood-brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19--all initially developed for other indications--are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood-brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date. PMID- 25112516 TI - Sponges associated with octocorals in the Indo-Pacific, with the description of four new species. AB - Sponges are characterised by high levels of phenotypic plasticity, thus allowing the same species to live in different habitats by taking different shapes. Here we describe 28 sponge species associated with the octocorals Carijoa riisei, Paratelesto rosea and Alertigorgia hoeksemai in Indonesia, Hawai'i and Vietnam, including four species that are new to science (Chondropsis subtilis, Hymedesmia (Hymedesmia) spinata, Hymedesmia (Stylopus) perlucida, Mycale (Aegogropila) furcata). Moreover, a large proportion of the described sponge species (21.4%) represent new records for the studied areas (Indonesia and Hawai'i). In total, we have studied 47 colonies of C. riisei associated with 24 sponge species, 5 colonies of P. rosea associated with 4 species and one colony of A. hoeksemai associated with one sponge species. Collectively, these examples of associations highlight the importance of epibiosis as a biodiversity enhancing process. PMID- 25112517 TI - Highly enantioselective catalytic system for asymmetric copolymerization of carbon dioxide and cyclohexene oxide. AB - A new ligand can be easily prepared, and its intramolecular dinuclear zinc complexes act as a high performance catalyst for the asymmetric alternating copolymerization of cyclohexene oxide and CO2 under very mild conditions (1 atm CO2 , room temperature), affording completely alternating polycarbonates with up to 93.8 % enantiomeric excess (ee) and 98 % yield. A high Mn value of 28 600 and a relatively narrow polydispersity (Mw /Mn ratio) of 1.43 were also achieved. PMID- 25112515 TI - Admixture mapping identifies a quantitative trait locus associated with FEV1/FVC in the COPDGene Study. AB - African Americans are admixed with genetic contributions from European and African ancestral populations. Admixture mapping leverages this information to map genes influencing differential disease risk across populations. We performed admixture and association mapping in 3,300 African American current or former smokers from the COPDGene Study. We analyzed estimated local ancestry and SNP genotype information to identify regions associated with FEV1 /FVC, the ratio of forced expiratory volume in one second to forced vital capacity, measured by spirometry performed after bronchodilator administration. Global African ancestry inversely associated with FEV1 /FVC (P = 0.035). Genome-wide admixture analysis, controlling for age, gender, body mass index, current smoking status, pack-years smoked, and four principal components summarizing the genetic background of African Americans in the COPDGene Study, identified a region on chromosome 12q14.1 associated with FEV1 /FVC (P = 2.1 * 10(-6) ) when regressed on local ancestry. Allelic association in this region of chromosome 12 identified an intronic variant in FAM19A2 (rs348644) as associated with FEV1 /FVC (P = 1.76 * 10(-6) ). By combining admixture and association mapping, a marker on chromosome 12q14.1 was identified as being associated with reduced FEV1 /FVC ratio among African Americans in the COPDGene Study. PMID- 25112518 TI - Design and characterization of a twin ribozyme for potential repair of a deletion mutation within the oncogenic CTNNB1-DeltaS45 mRNA. AB - RNA repair is an emerging strategy for gene therapy. Conventional gene therapy typically relies on the addition of the corrected DNA sequence of a defective gene to restore gene function. As an additional option, RNA repair allows alteration of the sequence of endogenous messenger RNAs (mRNAs). mRNA sequence alteration is either facilitated by intracellular spliceosome machinery or by the intrinsic catalytic activity of trans-acting ribozymes. Previously we developed twin ribozymes, derived from the hairpin ribozyme, by tandem duplication and demonstrated their potential for patchwise RNA repair. Herein we describe the development of such a twin ribozyme for potential repair of a deletion mutation in the oncogenic CTNNB1-DeltaS45 mRNA. We demonstrate that hairpin ribozyme units within the twin ribozyme can be adapted to efficiently cleave/ligate non consensus substrates by introduction of compensatory mutations in the ribozyme. Thus, we show the twin ribozyme mediated repair of truncated CTNNB1 transcripts (up to 1000 nt length). Repair of the entire CTNNB1-DeltaS45 mRNA, although apparently possible in general, is hampered in vitro by the secondary structure of the transcript. PMID- 25112514 TI - Selenium-enriched Spirulina protects INS-1E pancreatic beta cells from human islet amyloid polypeptide-induced apoptosis through suppression of ROS-mediated mitochondrial dysfunction and PI3/AKT pathway. AB - PURPOSE: Human islet amyloid polypeptide (hIAPP) aggregation is linked to loss of pancreatic beta cells in type 2 diabetes, in part due to oxidative stress. Currently, little is known about the effects of selenium-enriched Spirulina on beta cells with the presence of hIAPP. In this study, INS-1E rat insulinoma cells were used as a model to evaluate in vitro protective effects of Se-enriched Spirulina extract (Se-SE) against hIAPP-induced cell death, as well as the underlying mechanisms. METHODS: Flow cytometric analysis was used to evaluate cell apoptosis, mitochondrial membrane potential (DeltaPsim) and ROS generation. Caspase activity was measured using a fluorometric method. Western blotting was applied to detect protein expression. RESULTS: Our results showed that exposure of INS-1E cells to hIAPP resulted in cell viability loss, LDH release and appearance of sub-G peak. However, cytotoxicity of hIAPP was significantly attenuated by co-treatment with Se-SE. Se-SE also inhibited hIAPP-induced activation of caspase-3, -8 and -9. Additionally, hIAPP-induced accumulation of ROS and superoxide was suppressed by co-treatment with Se-SE. Moreover, Se-SE was able to prevent hIAPP-induced depletion of DeltaPsim and intracellular ATP, reduction in mitochondrial mass, changes in the expression of Bcl-2 family members, release of mitochondrial apoptogenic factors. Furthermore, hIAPP mediated AKT inhibition was restored by co-treatment with Se-SE. CONCLUSION: Our results showed that Se-SE protects INS-1E cells from hIAPP-induced cell death through preventing ROS overproduction, mitochondrial dysfunction and modulating PI3K/AKT pathway. PMID- 25112519 TI - Sulfur(VI) fluoride exchange (SuFEx): another good reaction for click chemistry. AB - Aryl sulfonyl chlorides (e.g. Ts-Cl) are beloved of organic chemists as the most commonly used S(VI) electrophiles, and the parent sulfuryl chloride, O2 S(VI) Cl2 , has also been relied on to create sulfates and sulfamides. However, the desired halide substitution event is often defeated by destruction of the sulfur electrophile because the S(VI) ?Cl bond is exceedingly sensitive to reductive collapse yielding S(IV) species and Cl(-) . Fortunately, the use of sulfur(VI) fluorides (e.g., R-SO2 -F and SO2 F2 ) leaves only the substitution pathway open. As with most of click chemistry, many essential features of sulfur(VI) fluoride reactivity were discovered long ago in Germany.6a Surprisingly, this extraordinary work faded from view rather abruptly in the mid-20th century. Here we seek to revive it, along with John Hyatt's unnoticed 1979 full paper exposition on CH2 ?CH-SO2 -F, the most perfect Michael acceptor ever found.98 To this history we add several new observations, including that the otherwise very stable gas SO2 F2 has excellent reactivity under the right circumstances. We also show that proton or silicon centers can activate the exchange of S?F bonds for S?O bonds to make functional products, and that the sulfate connector is surprisingly stable toward hydrolysis. Applications of this controllable ligation chemistry to small molecules, polymers, and biomolecules are discussed. PMID- 25112520 TI - Generation and characterization of Lhx9-GFPCreER(T2) knock-in mouse line. AB - LHX9 is a LIM-homeodomain transcription factor essential for the development of gonads, spinal cord interneurons, and thalamic neurons to name a few. We recently reported the expression of LHX9 in retinal amacrine cells during development. In this study, we generated an Lhx9-GFPCreER(T) (2) (GCE) knock-in mouse line by knocking-in a GCE cassette at the Lhx9 locus, thus inactivating endogenous Lhx9. Lhx9(GCE) (/+) mice were viable, fertile, and displayed no overt phenotypical characteristics. Lhx9(GCE) (/) (GCE) mice were all phenotypically female, smaller in size, viable, but infertile. The specificity and efficacy of the Lhx9-GCE mouse line was verified by crossing it to a Rosa26-tdTomato reporter mouse line, which reveals the Cre recombinase activities in retinal amacrine cells, developing limbs, testis, hippocampal neurons, thalamic neurons, and cerebellar neurons. Taken together, the Lhx9-GCE mouse line could serve as a beneficial tool for lineage tracing and gene manipulation experiments. genesis PMID- 25112522 TI - Standards of practice for clinical pharmacists: the time has come. PMID- 25112521 TI - The precuneus and visuospatial attention in near and far space: a transcranial magnetic stimulation study. AB - BACKGROUND: There is a large body of evidence for the involvement of the parietal cortex in orientation and navigation in space. This has been supplemented by investigation of the contribution of a number of subregions using transcranial magnetic stimulation. OBJECTIVE: The role of the precuneus area, located in the medial plane of posterior parietal cortex (PPC), in visuospatial functions is not well understood. We investigated the contribution of this area using the landmark task. METHODS: Participants were asked to make forced-choice judgments of which side of prebisected line was longer for near and far viewing conditions (70 and 180 cm, respectively). Online 10 Hz, repetitive transcranial magnetic stimulation (rTMS) was delivered for 500 ms over the right precuneus, rPPC and vertex (control), in separate blocks of trials. The rPPC stimulation was used as a positive control, having previously resulted in "neglect like" spatial bias effects in a number of studies. RESULTS: A no-TMS condition showed a leftward spatial bias (pseudoneglect) for near space judgments but not for far space and was used as the baseline. Precuneus stimulation resulted in rightward spatial bias from the midpoint in near space similar to the rPPC neglect-like effect. No significant effects were seen with vertex stimulation. CONCLUSION: This study shows that precuneus, like other parietal areas, is involved in visuospatial functions. Further work is required to clarify how the contribution of this area differs from other parietal regions. PMID- 25112523 TI - Standards of practice for clinical pharmacists. PMID- 25112524 TI - Does board certification really matter? PMID- 25112525 TI - Clinical pharmacy should adopt a consistent process of direct patient care. AB - Although the application of a consistent process of care serves as a foundational principle for most health care professions, this is not true for the discipline of clinical pharmacy. Without an explicit, reproducible process of care, it is not possible to demonstrate to patients, caregivers, or health professionals the ways in which the clinical pharmacist can reliably contribute to improved medication-related outcomes. A consistent patient care process should describe the key steps that all clinical pharmacists will follow when they encounter a patient, regardless of the type of practice, the clinical setting, or the medical conditions or medications involved. Four essential elements serve as the cornerstones of the clinical pharmacist's patient care process: assess the patient and his or her medication therapy, develop a plan of care, implement the plan, and evaluate the outcomes of the plan. Despite the fact that several processes of care have been advocated for clinical pharmacists, none has been adopted by the clinical pharmacy discipline. In addition, numerous publications evaluate outcomes related to clinical pharmacy services, but it is difficult to determine what process of patient care was used in most of these studies. In our view, a consistent process of direct patient care that includes the four essential elements should be adopted by the clinical pharmacy discipline. This process should be clear, straightforward and intuitive, readily documentable, and applicable to all practice settings. Once adopted, the process should be implemented across practice settings, taught in professional degree programs, integrated into students' clinical rotations, refined during residency training, and used as a foundation for future large-scale studies to rigorously study the effects of the clinical pharmacist on patients' medication-related outcomes. PMID- 25112526 TI - Successful use of octreotide as a chemoprotectant for prevention of PEG asparaginase-induced pancreatitis. AB - l-asparaginase is an aminohydrolase that deprives leukemia cells of l-asparagine required for protein synthesis. Although studies in patients with acute lymphoblastic leukemia have shown that the addition of l-asparaginase improved the overall remission rate, life-threatening acute pancreatitis has occurred in 0.5-4% of patients. We describe the first adult case report, to our knowledge, of the successful use of octreotide as a chemoprotectant for the prevention of recurrent pegylated asparaginase (PEG-ASP)-induced pancreatitis in a 21-year-old man with Philadelphia chromosome-negative acute lymphoblastic leukemia. After recurrent PEG-ASP administration during induction chemotherapy, he developed necrotizing pancreatitis, confirmed by abdominal computed tomography, and further asparaginase therapy was withheld. Currently, there are no specific treatment recommendations for the management of asparaginase-induced pancreatitis other than drug discontinuation. After disease relapse, a pediatric PEG-ASP-containing regimen was initiated, and PEG-ASP therapy was resumed due to its potential clinical benefit. Octreotide 100 MUg subcutaneously 3 times/day, utilized as a chemoprotectant, was found to prevent pancreatitis recurrence. The patient completed therapy and was able to receive a bone marrow transplant without further complications from PEG-ASP therapy. Based on this patient's experience, we believe it is reasonable to reincorporate PEG-ASP after an episode of pancreatitis with use of octreotide as a chemoprotectant; however, this conclusion will need to be substantiated in a randomized clinical trial with a larger group of patients. PMID- 25112527 TI - Alternative viewpoint: preparation for residency. PMID- 25112528 TI - Beta-blocker and antipsychotic treatment of toxicity from so-called designer drugs. PMID- 25112529 TI - Shaping of an effective immune microenvironment to and by cancer cells. AB - A high density of intratumoral effector memory CD8+/Th1 T cells is associated with favorable prognosis in most cancers and may be induced or increased by immunotherapy. Efficient adaptive immune reactions are shaped in tumor adjacent tertiary lymphoid structures, which exhibit all characteristics of immunity generating lymphoid formations in reactive lymph nodes. Malignant tumor cells impact favorably or deleteriously their immune microenvironment if they bear genetic mutations that result in neo-antigens or by producing chemokines and cytokines that recruit lymphocytes and myeloid cells or increase inflammation and neo-angiogenesis. This intricate network of interactions results in control or escape of tumors, and its understanding will help define goals to monitor efficiency of immunotherapies. PMID- 25112530 TI - Downregulation of microRNA-124 predicts poor prognosis in glioma patients. AB - The aim of the present study was to investigate the clinical significance of microRNA-124 (miR-124) expression in glioma. The expression levels of miR-124 were measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The correlation between the miR-124 levels and the clinicopathological factors of the glioma patients was analyzed. The survival curves were calculated by the Kaplan-Meier method. The influence of each variable on survival was examined by the Cox multivariate regression analysis. Compared with nonneoplastic brain tissues, the expression level of miR-124 was significantly decreased in glioma tissues (1.27 +/- 0.55 versus 6.91 +/- 1.06, P < 0.0001). The expression level of miR-124 was positively correlated with grade (P = 0.003) and Karnofsky performance status (KPS) score (P = 0.008). A significant difference was found that glioma patients with low miR-124 expression level had distinctly shorter OS (P = 0.001) and PFS (P = 0.002) than patients with high miR-124 expression level. Furthermore, we found that low miR-124 expression (OS P = 0.009; PFS P = 0.002) and advanced histologic grade (OS P = 0.005; PFS P = 0.001) were independent prognostic parameters indicating poor prognosis for glioma patients. Our results showed that the decreased expression of miR-124 may be associated with malignant tumor progression and poor prognosis in patients with gliomas, suggesting that miR-124 may be a novel and valuable signature for predicting the clinical outcome of patients with gliomas. PMID- 25112531 TI - Role of physical activity in reducing cognitive decline in older Mexican-American adults. AB - The effect of physical activity on cognitive function in older adults from minority and disadvantaged populations is not well understood. This study examined the longitudinal association between physical activity and cognition in older Mexican Americans. The study methodology included a prospective cohort with longitudinal analysis of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly. General linear mixed models were used to assess the associations and interactions between physical activity and cognitive function over 14 years. Community-based assessments were performed in participants' homes. Physical activity was recorded for 1,669 older Mexican Americans using the Physical Activity Scale for the Elderly. Cognition was measured using the Mini-Mental State Examination (MMSE) and separated into memory and nonmemory components. A statistically significant positive association was observed between levels of physical activity and cognitive function after adjusting for age, sex, marital status, education, and comorbid health conditions. There was a statistically significant difference in MMSE scores over time between participants in the third (beta = 0.11, standard error (SE) = 0.05) and fourth (beta = 0.10, SE = 0.2) quartiles of physical activity and those in the first. The protective effect of physical activity on cognitive decline was evident for the memory component of the MMSE but not the nonmemory component after adjusting for covariates. Greater physical activity at baseline was associated with less cognitive decline over 14 years in older Mexican Americans. The reduction in cognitive decline appeared to be related to the memory components of cognitive function. PMID- 25112532 TI - Modern extraction techniques and their impact on the pharmacological profile of Serenoa repens extracts for the treatment of lower urinary tract symptoms. AB - BACKGROUND: Bioactive compounds from plants (i.e., Serenoa repens) are often used in medicine in the treatment of several pathologies, among which benign prostatic hyperplasia (BPH) associated to lower urinary tract symptoms (LUTS). DISCUSSION: There are different techniques of extraction, also used in combination, with the aim of enhancing the amount of the target molecules, gaining time and reducing waste of solvents. However, the qualitative and quantitative composition of the bioactives depends on the extractive process, and so the brands of the recovered products from the same plant are different in terms of clinical efficacy (no product interchangeability among different commercial brands). SUMMARY: In this review, we report on several and recent extraction techniques and their impact on the composition/biological activity of S. repens-based available products. PMID- 25112533 TI - A multi-institution evaluation of MLC log files and performance in IMRT delivery. AB - BACKGROUND: The multileaf collimator (MLC) is a critical component to accurate intensity-modulated radiotherapy (IMRT) delivery. This study examined MLC positional accuracy via MLC logs from Varian machines from six institutions and three delivery techniques to evaluate typical positional accuracy and treatment and mechanical parameters that affect accuracy. Typical accuracy achieved was compared against TG-142 recommendations for MLC performance; more appropriate recommendations are suggested. METHODS: Over 85,000 Varian MLC treatment logs were collected from six institutions and analyzed with FractionCHECK. Data were binned according to institution and treatment type to determine overall root mean square (RMS) and 95th percentile error values, and then to look for correlations between those errors and with mechanical and treatment parameters including mean and maximum leaf speed, gantry angle, beam-on time, mean leaf error, and number of segments. RESULTS: Results of treatment logs found that leaf RMS error and 95th percentile leaf error were consistent between institutions, but varied by treatment type. The step and shoot technique had very small errors: the mean RMS leaf error was 0.008 mm. For dynamic treatments the mean RMS leaf error was 0.32 mm, while volumetric-modulated arc treatment (VMAT) showed an RMS leaf error of 0.46 mm. Most MLC leaf errors were found to be well below TG-142 recommended tolerances. For the dynamic and VMAT techniques, the mean and maximum leaf speeds were significantly linked to the leaf RMS error. Additionally, for dynamic delivery, the mean leaf error was correlated with RMS error, whereas for VMAT the average gantry speed was correlated. For all treatments, the RMS error and the 95th percentile leaf error were correlated. CONCLUSIONS: Restricting the maximum leaf speed can help improve MLC performance for dynamic and VMAT deliveries. Furthermore, the tolerances of leaf RMS and error counts for all treatment types should be tightened from the TG-142 values to make them more appropriate for clinical performance. Values of 1 mm for the 95th percentile of leaf RMS error and 1.5 mm for the 95th percentile leaf error are suggested as action levels for all treatment types. PMID- 25112534 TI - Direct comparison of the different conventional laparoscopic positions with the ethos surgical platform in a laparoscopic pelvic surgery simulation setting. AB - OBJECTIVE: Laparoscopic surgery can be harmful to surgeons requiring a prolonged learning curve due to significant ergonomic drawbacks. Based on preliminary clinical experience, we present an experimental evaluation of the second generation ETHOSTM operating chair by comparing it with two different operating positions of conventional laparoscopic pelvic surgery. MATERIALS AND METHODS: The ETHOS operation platform consists of a seat like a saddle and five more parts that can be adjusted individually to support the surgeon's trunk and extremities. This operation platform was tested in 30 trainees who performed three standard suturing exercises in a pelvitrainer, approximating a linear and a U-shaped incision, made on the skin of a chicken leg, and completing an urethrovesical anastomosis, on a pig bladder specimen model, using interrupted sutures. The trainees performed each exercise in standing laterally to pelvitrainer (torero position) vs standing behind pelvi-trainer and sitting on ETHOS. The mean values, from all times and for each exercise and position, were documented, and the participants filled out a validated questionnaire focusing on ergonomic issues. RESULTS: There were no significant differences among the different training modalities, in step 1 and step 2. However, in step 3, which mimics the urethrovesical anastomosis, the mean times were statistically significant significantly less by using ETHOS (p<0.0001). The mean times of training in step 3 were 41.2 minutes in the behind the camera position, 49 minutes in torero position, and 39.7 minutes by using ETHOS. The position that was maintained, during the exercises, was mainly responsible for the improvement noted in the ergonomic scores. CONCLUSIONS: The new operating platform (ETHOS chair) can significantly improve ergonomics in laparoscopy particularly concerning difficult steps like intracorporeal suturing. This may also improve the urethrovesical anastomosis times in a clinical setting. PMID- 25112536 TI - Survey of Victorian ophthalmologists who use ranibizumab to treat age-related macular degeneration: to identify current practice and modifiable risk factors relevant to post-injection endophthalmitis. PMID- 25112535 TI - Now you see it, now you don't: Testing environments modulate the association between hippocampal volume and cortisol levels in young and older adults. AB - The hypothalamic pituitary adrenal axis production of the stress hormone cortisol interacts with the hippocampal formation and impacts memory function. A growing interest is to determine whether hippocampal volume (HV) predicts basal and/or reactive cortisol levels in young and older adults. Recent evidence shows that contextual features in testing environments might be stressful and inadvertently induce a stress response in young and/or older populations. This latter result suggests that variations in testing environments might influence associations between HV and cortisol levels in young and older adults. To this end, we investigated 28 healthy young adults (ages 18-35) and 32 healthy older adults (ages 60-75) in two different environments constructed to be more or less stressful for each age group (Favoring-Young versus Favoring-Old conditions). Cortisol levels were repeatedly assessed in each environment, and young and older participants underwent an anatomical magnetic resonance imaging scan for subsequent assessment of HV. Results in both age groups showed that HV was significantly associated with cortisol levels only in the unfavorable stressful testing conditions specific for each age group. This association was absent when testing environments were designed to decrease stress for each age group. These findings are fundamental in showing that unless the nature of the testing environment is taken into consideration, detected associations between HV and cortisol levels in both young and older populations might be confounded by environmental stress. PMID- 25112537 TI - Nanocomplexes based on amphiphilic hyaluronic acid derivative and polyethylene glycol-lipid for ginsenoside rg3 delivery. AB - Hybrid nanocomplex formulations, based on amphiphilic hyaluronic acid-ceramide (HACE) and lipids, were fabricated for the delivery of 20(S)-ginsenoside Rg 3 [(S)-Rg3]. Nanocomplexes with less than 200 nm mean diameter, narrow size distribution, spherical shape, and negative zeta potential were prepared. The maintenance of the structural stability of the hybrid nanocomplexes in the blood stream was demonstrated by measuring their particle size in serum. Nanocomplexes based on HACE, phosphatidylcholine (PC), and 1,2-distearoyl-sn-glycero-3 phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) showed a sustained drug release profile compared with other formulations. Blank nanocomplexes exhibited negligible cytotoxicity within the tested concentration range in A549 human lung adenocarcinoma cells. The cellular uptake efficiency of hybrid nanocomplexes was improved compared with the HACE-based nanoparticles probably because of interactions between lipids and the cellular membrane. The results of a pharmacokinetic study in rats revealed decreased in vivo clearance of (S)-Rg3, especially in the HACE/PC/DSPE-PEG-based hybrid nanocomplex (F3) group. The hybrid nanostructure and the outer PEG chain likely contributed to improve in vivo performance of the F3 group. Thus, these developed hybrid nanocomplexes could serve as good candidates for tumor-targeted delivery of anticancer agents. PMID- 25112538 TI - Hyperuricemia and chronic kidney disease: an enigma yet to be solved. AB - The role of uric acid (UA) on the pathogenesis and progression of chronic kidney disease (CKD) remains controversial. Experimental and clinical studies indicate that UA is associated with several risk factors of CKD including diabetes, hypertension, oxidative stress, and inflammation and hyperuricemia could be considered as a common dominator linking CKD and cardiovascular disease. Notably, the impact of serum UA levels on the survival of CKD, dialysis patients, and renal transplant recipients is also a matter of debate, as there are conflicting results from clinical studies. At present, there is no definite data whether UA is causal, compensatory, coincidental or it is only an epiphenomenon in these patients. In this article, we attempt to review and elucidate the dark side of this old molecule in CKD and renal transplantation. PMID- 25112539 TI - Metal artefact reduction algorithms prevent false positive results when assessing patients for cardiac implantable electronic device infection. AB - Software-based metal artefact reduction (MAR) techniques are available to reduce artefacts from cardiac implantable electronic devices (CIED) in the CT data. The impact of disabling MAR techniques on quantification of 18F-FDG uptake around the CIED has not been examined. We consider the importance of enabling MAR in patients with suspected CIED infection to prevent inaccuracies in quantification of tissue tracer uptake on the attenuation-corrected PET images. PMID- 25112540 TI - The potential role of gated myocardial perfusion SPECT imaging in patient selection for cardiac resynchronization therapy. PMID- 25112541 TI - Evaluation of the breeding soundness of male camels (Camelus dromedarius) via clinical examination, semen analysis, ultrasonography and testicular biopsy: a summary of 80 clinical cases. AB - Male camel infertility is a heterogeneous disorder. A variety of factors may adversely affect sperm production and function and impair fertility. This study was designed to evaluate the sensitivity and specificity of ultrasonography and testicular biopsy in the evaluation of the breeding soundness of male dromedaries compared with results obtained by clinical examination and semen analysis. Eighty four male dromedary camels (5-15 years old) were used in this study during the rutting season (November-May). Four sexually mature male camels were used as controls. These animals were apparently healthy and had histories of normal fertility. Eighty infertile male camels were subjected to an algorithmic approach based on information collected during careful examinations of the camels' breeding histories, clinical examinations, testicular evaluations, testicular ultrasonographies, the results of the semen analyses and testicular biopsies to diagnose the camels' infertilities. The differences in the semen parameters between the control and infertile male camels were highly significant (p < 0.01). Regarding the diagnoses of male camel infertility, the results of testicular ultrasonographies and biopsies were compared with those from the semen analyses, and the accuracies of these tests were 92.5% and 90%, respectively. Additionally, the results of the testicular ultrasonographies were matched with those of the testicular biopsies of the infertile animals, and this comparison resulted in 85% accuracy. Testicular biopsy is a promising method that, along with a carefully performed history, clinical examination, an appropriate testicular ultrasonography procedure and semen analysis, can afford veterinarians the opportunity for more precise diagnosis and treatment of many dromedary infertility disorders. PMID- 25112543 TI - Ophthalmoplegia in congenital neuromuscular disease with uniform type 1 fiber. AB - Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) is a rare type of congenital myopathy. It is characterized by early onset of symptoms, mild proximal muscle weakness, hyporeflexia or areflexia, normal serum creatine kinase (CK) levels and myopathic electromyography finding, uniform type 1 fibers, and nonprogression. We report a 2-year-old boy who presented with congenital hypotonia, breathing and feeding difficulty, myopathic facies, proximal muscle weakness, ptosis, total external ophthalmoplegia and delayed motor developmental milestones. Normal serum muscle enzyme and short duration of motor unit potentials on electromyography were noted. Muscle biopsy showed uniformity of type 1 fibers (greater than 99%) and moderate variation in fiber size without specific structural abnormality. Total external ophthalmoplegia may be one of the important clinical manifestations of CNMDU1. It is important to recognize this disorder because it is nonprogressive in nature. PMID- 25112542 TI - Pharmacological management of central post-stroke pain: a practical guide. AB - Pain is one of the most troublesome sequelae of stroke. Some of this post-stroke pain is caused by the brain lesion itself; this is called central post-stroke pain (CPSP). Although the prevalence of CPSP is low (1-8 %), persistent, often treatment-resistant, painful sensations are a major problem for stroke patients. The pathogenesis of CPSP remains unknown, but suggested underlying causes include hyperexcitation in the damaged sensory pathways, damage to the central inhibitory pathways, or a combination of the two. For pharmacological treatment, amitriptyline, an adrenergic antidepressant, is currently the first-line drug for CPSP. However, its effect is frequently incomplete and a high dose is commonly not tolerated in stroke patients. Lamotrigine, an antiepileptic, was also found to be effective in a controlled trial and can be used as an alternative or additive therapy. GABAergic drugs with potential calcium channel-blocking effects, such as gabapentin or pregabalin, have recently emerged as a potentially useful therapy. These drugs are effective in various neuropathic pain syndromes, but their effect on CPSP remains to be proven. Pregabalin may improve pain related anxiety and sleep disturbances. Fluvoxamine and mexiletine may be used adjunctively in some patients. Non-pharmacological treatments such as motor cortex stimulation or deep brain stimulation are used in some centers, but are not proven to be effective. Further well designed clinical trials as well as basic research should be performed to improve our understanding of the pathophysiology of CPSP and to develop better treatment strategies. PMID- 25112544 TI - A resting state functional magnetic resonance imaging study of concussion in collegiate athletes. AB - Sports-related concussions are currently diagnosed through multi-domain assessment by a medical professional and may utilize neurocognitive testing as an aid. However, these tests have only been able to detect differences in the days to week post-concussion. Here, we investigate a measure of brain function, namely resting state functional connectivity, which may detect residual brain differences in the weeks to months after concussion. Twenty-one student athletes (9 concussed within 6 months of enrollment; 12 non-concussed; between ages 18 and 22 years) were recruited for this study. All participants completed the Wisconsin Card Sorting Task and the Color-Word Interference Test. Neuroimaging data, specifically resting state functional Magnetic Resonance Imaging data, were acquired to examine resting state functional connectivity. Two sample t-tests were used to compare the neurocognitive scores and resting state functional connectivity patterns among concussed and non-concussed participants. Correlations between neurocognitive scores and resting state functional connectivity measures were also determined across all subjects. There were no significant differences in neurocognitive performance between concussed and non concussed groups. Concussed subjects had significantly increased connections between areas of the brain that underlie executive function. Across all subjects, better neurocognitive performance corresponded to stronger brain connectivity. Even at rest, brains of concussed athletes may have to 'work harder' than their healthy peers to achieve similar neurocognitive results. Resting state brain connectivity may be able to detect prolonged brain differences in concussed athletes in a more quantitative manner than neurocognitive test scores. PMID- 25112545 TI - Filter wire fracture during transradial carotid stenting. PMID- 25112546 TI - Poor response to antidepressants predicts new suicidal ideas and behavior in depressed outpatients. AB - BACKGROUND: Only a few studies have investigated the factors associated with suicidal behavior after antidepressant treatment onset in adults. We examined the specific predictors of de novo suicidal ideas or attempts among depressed patients in the community, including subjects potentially at risk of suicidal behaviors, who initiated a new antidepressant treatment. METHODS: A large set of GPs and psychiatrists throughout France followed-up, for 6 weeks, 4357 outpatients for whom an antidepressant drug was prescribed. Dimensions related with antidepressant-induced suicidal events, such as depression, anxiety or hopelessness, were assessed longitudinally using univariate and multivariate approaches among subjects with treatment-emergent suicide ideation or attempts. RESULTS: New suicidal ideas were observed in 9% of patients with no suicidal ideation at baseline (n=81), while suicidal attempts were reported for 1.7% of the sample during the 6-week observation period (n=75). The onset of suicidal ideas and attempts was associated with the initial features of the patients (baseline level of anxiety, past history of suicide attempts and alcohol misuse) and the non-improvement of depression. Worsening of depressive symptoms during the follow-up increased the onset of new suicidal ideas (OR=5.67, p<0.001) and attempts (OR=2.60, p=0.002), corresponding to 67.5% and 56.5% of attributable risk respectively. CONCLUSIONS: When the analyses are restricted to the occurrence of suicidal ideas or attempts, the link between antidepressants and suicide risk might be more adequately explained by a poor response to antidepressant treatment rather than by a direct trigger-effect. This naturalistic study is limited by the use of non-structured diagnoses and self report outcomes. PMID- 25112547 TI - [Prevalence of sleep disorders and associated factors in inpatient]. AB - OBJECTIVE: To determine the prevalence of insomnia in inpatient in an Internal Medicine Department and to identify risk factors of sleep disorders. METHOD: A cross-sectional observational study was designed. Inpatients over eighteen years old hospitalized for acute medical conditions were recruited. Insomnia was assessed by the Athens insomnia scale. A nurse administered a questionnaire on risk factors including socio-demographic factors, reason for admission, comorbidities, current medications, functional status, nocturnal symptoms, and environmental factors. RESULTS: A total of 299 patients were recruited with a mean age of 73.7 years (SD 14.2). Overall prevalence of insomnia was 42.1%, slightly higher in women (48.2%) than in men (37.0%) (P=.052). In those less than 65 years the prevalence was 33.8%, and in patients aged 65 or over it was 44.9% (P=.093). The main factors associated with insomnia were a history of anxiety, depression and stroke, heartburn, pain, fear, and poor functional capacity at admission. Environmental factors such as noise, the sensation of cold or heat, and changing habits involved in hospitalization did not reach statistical significance. In patients 65 years or older, the use of beta-blockers was associated with insomnia. The multivariate analysis showed stroke, heartburn, and pain as independent risk factors for insomnia. CONCLUSIONS: Insomnia is highly prevalent among inpatient, and is associated with some treatable or modifiable factors. PMID- 25112548 TI - The detection of neural autoantibodies in patients with antiepileptic-drug resistant epilepsy predicts response to immunotherapy. AB - BACKGROUND AND PURPOSE: The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of 'autoimmune epilepsy'. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy. METHODS: Eighty-one patients and 75 age- and sex matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency. RESULTS: Neural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency. CONCLUSIONS: A significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance. PMID- 25112549 TI - Minocycline protects against oxidative damage and alters energy metabolism parameters in the brain of rats subjected to chronic mild stress. AB - Studies have been suggested that minocycline can be a potential new agent for the treatment of depression. In addition, both oxidative stress and energy metabolism present an important role in pathophysiology of depression. So, the present study was aimed to evaluate the effects of minocycline on stress oxidative parameters and energy metabolism in the brain of adult rats submitted to the chronic mild stress protocol (CMS). After CMS Wistar, both stressed animals as controls received twice ICV injection of minocycline (160 MUg) or vehicle. The oxidative stress and energy metabolism parameters were assessed in the prefrontal cortex (PF), hippocampus (HIP), amygdala (AMY) and nucleus accumbens (Nac). Our findings showed that stress induced an increase on protein carbonyl in the PF, AMY and NAc, and mynocicline injection reversed this alteration. The TBARS was increased by stress in the PF, HIP and NAc, however, minocycline reversed the alteration in the PF and HIP. The Complex I was incrased in AMY by stress, and minocycline reversed this effect, however reduced Complex I activity in the NAc; Complex II reduced in PF and AMY by stress or minocycline; the Complex II-III increased in the HIP in stress plus minocycline treatment and in the NAc with minocycline; in the PF and HIP there were a reduced in Complex IV with stress and minocycline. The creatine kinase was reduced in AMY and NAc with stress and minocycline. In conclusion, minocycline presented neuroprotector effects by reducing oxidative damage and regulating energy metabolism in specific brain areas. PMID- 25112551 TI - N-nitrosodimethylamine (NDMA) formation potential of amine-based water treatment polymers: Effects of in situ chloramination, breakpoint chlorination, and pre oxidation. AB - Recent studies show that cationic amine-based water treatment polymers may be important precursors that contribute to formation of the probable human carcinogen N-nitrosodimethylamine (NDMA) during water treatment and disinfection. To better understand how water treatment parameters affect NDMA formation from the polymers, the effects of in situ chloramination, breakpoint chlorination, and pre-oxidation on the NDMA formation from the polymers were investigated. NDMA formation potential (NDMA-FP) as well as dimethylamine (DMA) residual concentration were measured from poly(epichlorohydrin dimethylamine) (polyamine) and poly(diallyldimethylammonium chloride) (polyDADMAC) solutions upon reactions with oxidants including free chlorine, chlorine dioxide, ozone, and monochloramine under different treatment conditions. The results supported that dichloramine (NHCl2) formation was the critical factor affecting NDMA formation from the polymers during in situ chloramination. The highest NDMA formation from the polymers occurred near the breakpoint of chlorination. Polymer chain breakdown and transformation of the released DMA and other intermediates were important factors affecting NDMA formation from the polymers in pre-oxidation followed by post-chloramination. Pre-oxidation generally reduced NDMA-FP of the polymers; however, the treatments involving pre-ozonation increased polyDADMAC's NDMA-FP and DMA release. The strategies for reducing NDMA formation from the polymers may include the avoidance of the conditions favorable to NHCl2 formation and the avoidance of polymer exposure to strong oxidants such as ozone. PMID- 25112550 TI - Competitive antagonism of insect GABA receptors by 4-substituted 5-(4-piperidyl) 3-isothiazolols. AB - gamma-Aminobutyric acid (GABA) receptors are important targets of parasiticides/insecticides. Several 4-substituted analogs of the partial GABAA receptor agonist 5-(4-piperidyl)-3-isothiazolol (Thio-4-PIOL) were synthesized and examined for their antagonism of insect GABA receptors expressed in Drosophila S2 cells or Xenopus oocytes. Thio-4-PIOL showed weak antagonism of three insect GABA receptors. The antagonistic activity of Thio-4-PIOL was enhanced by introducing bicyclic aromatic substituents into the 4-position of the isothiazole ring. The 2-naphthyl and the 3-biphenylyl analogs displayed antagonist potencies with half maximal inhibitory concentrations in the low micromolar range. The 2-naphthyl analog induced a parallel rightward shift of the GABA concentration-response curve, suggesting competitive antagonism by these analogs. Both compounds exhibited weak insecticidal activities against houseflies. Thus, the orthosteric site of insect GABA receptors might be a potential target site of insecticides. PMID- 25112552 TI - Investigation of potential soil contamination with Cr and Ni in four metal finishing facilities at Asopos industrial area. AB - The objective of this work was to investigate whether previous disposal practices in four metal finishing facilities, located at Asopos river basin (East-Central Greece), have caused any potential serious contamination of soils. The study focused mainly on Cr and Ni, which are the primary elements of concern in the area. To estimate the natural geochemical levels of Cr and Ni, thirty soil samples were collected from locations that were not suspected of any contamination. In this group of samples, Cr concentration varied between 60 and 418 mg/kg, and Ni concentrations varied from 91 to 1200 mg/kg. The second group of samples consisted of more than 100 drill cores and surface soil samples, potentially affected by the disposal of effluents and/or the drainage of runoff water from the industrial facilities. According to the findings of the study, the disposal of treated effluents in absorption type sinks resulted occasionally in the contamination of a thin layer of soil just at the bottom of the sinks, but there was no indication of downward migration, since Cr and Ni concentrations in the lower soil layers were similar to those of the reference soils. PMID- 25112554 TI - Physical activity below the minimum international recommendations improves oxidative stress, ADMA levels, resting heart rate and small artery endothelial function. AB - BACKGROUND: A moderate level of physical activity (PA), such as a daily 30-min walk, reduces cardiovascular risk. There is a lack of evidence about the cardiovascular benefits of PA below this recommendation of minimum PA level. OBJECTIVE: We aimed to study the impact of a lower level of PA on cardiovascular health. DESIGN: Sixty-four overweight/obese men and women were enrolled in a community programme consisting of 4 months of 1h, low-intensity PA two days per week. Before and after the intervention, PA level (METs/h/wk), endogenous antioxidant status (SOD and GPX concentration and activity and oxidised LDL), ADMA concentrations, endothelial function by small artery reactive hyperaemia index (saRHI), and resting heart rate (RHR) were assessed. RESULTS: After the intervention, significant increases in saRHI (P=0.031), SOD and GPX activities, and a decrease in ADMA plasma concentrations, and RHR (P<0.001 for all) were observed. Increases in PA were positively associated with increases in saRHI (r=0.341, P=0.022), GPx (r=0.303, P=0.047) and decreases in RHR (r=-0.302, P=0.047). Multivariate analyses showed that independent predictors of saRHI improvement were an increase in PA (2.65, 95%CI: 1.21-4.01), decrease in RHR (1.91, 95%CI: 1.01-4.98), and an increase in GPx (2.61, 95%CI: 1.16-5.01). CONCLUSION: In obese and overweight men and women, an increase in PA, even below the minimal international recommendations, improves antioxidant capacity, RHR and peripheral small artery reactivity. PMID- 25112555 TI - Trends in the incidence and management of acute myocardial infarction from 1999 to 2008: get with the guidelines performance measures in Taiwan. AB - BACKGROUND: The American Heart Association Get With the Guidelines (GWTG) program has improved care quality of acute myocardial infarction (AMI) with important implications for other countries in the world. This study evaluated the incidence and care of AMI in Taiwan and assessed the compliance of GWTG in Taiwan. METHODS AND RESULTS: We used the Taiwan National Health Insurance Research Database (1999 2008) to identify hospitalized patients >=18 years of age presenting with AMI. The temporal trends of annual incidence and care quality of AMI were evaluated. The age-adjusted incidence of AMI (/100 000 person-years) increased from 28.0 in 1999 to 44.4 in 2008 (P<0.001). The use of guideline-based medications for AMI was evaluated. The use of dual antiplatelet therapy (DAPT) increased from 65% in 2004 to 83.9% in 2008 (P<0.001). Angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) was used in 72.6% in 2004 and 71.7% in 2008 (P=NS) and beta-blocker was used in 60% in 2004 and 59.7% in 2008 (P=NS). Statin use increased from 32.1% to 50.1% from 2004 to 2008 (P<0.001). The in-hospital mortality decreased from 15.9% in 1999 to 12.3% in 2008 (P<0.0001). Multivariable analysis showed that DAPT, ACE inhibitor/ARB, beta-blocker, and statin use during hospitalization were all associated with reduced in-hospital mortality in our AMI patients. CONCLUSIONS: AMI incidence was increasing, but the guideline-based medications for AMI were underutilized in Taiwan. Quality improvement programs, such as GWTG, should be promoted to improve AMI care and outcomes in Taiwan. PMID- 25112556 TI - Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification and vascular territory of ischemic stroke lesions diagnosed by diffusion-weighted imaging. AB - BACKGROUND: The association between the location and the mechanism of a stroke lesion remains unclear. A diffusion-weighted imaging study may help resolve this lack of clarity. METHODS AND RESULTS: We studied a consecutive series of 2702 acute ischemic stroke patients whose stroke lesions were confirmed by diffusion weighted imaging and who underwent a thorough etiological investigation. The vascular territory in which an ischemic lesion was situated was identified using standard anatomic maps of the dominant arterial territories. Stroke subtype was based on the Trial of ORG 10172 in Acute Stroke Treatment, or TOAST, classification. Large-artery atherosclerosis (37.3%) was the most common stroke subtype, and middle cerebral artery (49.6%) was the most frequently involved territory. Large-artery atherosclerosis was the most common subtype for anterior cerebral, middle cerebral, vertebral, and anterior and posterior inferior cerebellar artery territory infarctions. Small vessel occlusion was the leading subtype in basilar and posterior cerebral artery territories. Cardioembolism was the leading cause in superior cerebellar artery territory. Compared with carotid territory stroke, vertebrobasilar territory stroke was more likely to be caused by small vessel occlusion (21.4% versus 30.1%, P<0.001) and less likely to be caused by cardioembolism (23.2% versus 13.8%, P<0.001). Multiple-vascular territory infarction was frequently caused by cardioembolism (44.2%) in carotid territory and by large-artery atherosclerosis (52.1%) in vertebrobasilar territory. CONCLUSIONS: Information on vascular territory of a stroke lesion may be helpful in timely investigation and accurate diagnosis of stroke etiology. PMID- 25112557 TI - The prevalence and subjective handicap of epilepsy in Ilie--a rural riverine community in South West Nigeria: a door-to-door survey. AB - BACKGROUND: The prevalence of epilepsy is high in tropical countries, particularly in Africa with an estimated mean prevalence of 15 per 1000. There is lack of recent data on epilepsy prevalence in Nigeria. The main objective of this study was to determine the prevalence of epilepsy in Ilie in South West (SW) Nigeria, and the secondary objectives were to determine the clinical characteristics, the seizure types with electroencephalography (EEG) recording, the pattern of treatment, and to evaluate the subjective handicap of people with epilepsy (PWE). MATERIALS AND METHODS: The study, which was descriptive cross sectional, was carried out in Ilie, a rural community in South West Nigeria, using a simple random sampling technique. The survey was done in 2 phases from January 2013 to April 2013. Phase 1: Door-to-door screening using the WHO Neuroscience Research Protocol to detect neurological disorders by health workers. Phase 2: Individuals with positive screening had complete neurologic examination by neurologists as well as an EEG recording. The questionnaires for survey of epilepsy in tropical countries and subjective handicap of epilepsy were administered to all PWE. RESULTS: Two thousand two hundred twelve individuals from 231 households were screened during the first phase, and 33 cases of neurologic diseases were detected. During the second phase, 10 cases were confirmed to be epilepsy by neurologists, thus giving a crude lifetime prevalence of 10/2212=4.5/1000 population (95% CI=2.30-8.04). CONCLUSIONS: The prevalence of epilepsy in Ilie in South West Nigeria is rather low compared with previous figures from studies in rural Africa. PMID- 25112558 TI - Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats. AB - Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. However, mounting preclinical evidence suggests that even brief exposure to phenobarbital in the neonatal period can induce neuronal apoptosis, alterations in synaptic development, and long-lasting changes in behavioral functions. In the present report, we treated neonatal rat pups with phenobarbital and evaluated behavior in adulthood. Pups were treated initially with a loading dose (80 mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and conditioned place preference for cocaine when the animals reached adulthood. Consistent with our previous reports, we found that three days of neonatal exposure to phenobarbital significantly impaired prepulse inhibition compared with vehicle-exposed control animals. Using a step-though passive avoidance paradigm, we found that animals exposed to phenobarbital as neonates and tested as adults showed significant deficits in passive avoidance retention compared with matched controls, indicating impairment in associative memory and/or recall. Finally, we examined place preference conditioning in response to cocaine. Phenobarbital exposure did not alter the normal conditioned place preference associated with cocaine exposure. Our findings expand the profile of behavioral toxicity induced by phenobarbital. PMID- 25112559 TI - Behavioural weight management programmes for adults assessed by trials conducted in everyday contexts: systematic review and meta-analysis. AB - This systematic review and meta-analysis of effectiveness trials comparing multicomponent behavioural weight management programmes with controls in overweight and obese adults set out to determine the effectiveness of these interventions implemented in routine practice. To be included, interventions must have been multicomponent, delivered by the therapists who would deliver the intervention in routine practice and in that same context, and must be widely available or feasible to implement with little additional infrastructure or staffing. Searches of electronic databases were conducted, and augmented by screening reference lists and contacting experts (November 2012). Data were extracted by two reviewers, with mean difference between intervention and control for 12-month change in weight, blood pressure, lipids and glucose calculated using baseline observation carried forward. Data were also extracted on adverse events, quality of life and mood measures. Although there were many published efficacy trials, only eight effectiveness trials met the inclusion criteria. Pooled results from five study arms providing access to commercial weight management programmes detected significant weight loss at 12 months (mean difference -2.22 kg, 95% confidence interval [CI] -2.90 to -1.54). Results from two arms of a study testing a commercial programme providing meal replacements also detected significant weight loss (mean difference -6.83 kg, 95% CI -8.39 to 5.26). In contrast, pooled results from five interventions delivered by primary care teams showed no evidence of an effect on weight (mean difference -0.45 kg, 95% CI -1.34 to 0.43). One study testing an interactive web-based intervention detected a significant effect in favour of the intervention at 12 months, but the study was judged to be at high risk of bias and the effect did not persist at 18 months. Few studies reported other outcomes, limiting comparisons between interventions. Few trials have examined the effectiveness of behavioural weight loss programmes delivered in everyday contexts. These trials suggest that commercial interventions delivered in the community are effective for achieving weight loss. There is no evidence that interventions delivered within primary care settings by generalist primary care teams trained in weight management achieve meaningful weight loss. PMID- 25112560 TI - Changes in sleep and fatigue in newly treated pediatric oncology patients. AB - BACKGROUND: Fatigue has been reported as one of the most distressing symptoms in oncology patients, yet few have investigated the longitudinal course of sleep and fatigue in newly diagnosed pediatric oncology patients. PROCEDURE: To longitudinally assess presence and changes of sleep complaints and fatigue, we administered questionnaires designed to measure sleep complaints, sleep habits, daytime sleepiness, and fatigue to parents of pediatric oncology patients ages 2 18 and to pediatric oncology patients, themselves, ages 8-18 within 30 days of diagnosis (n = 170) and again 8 weeks later (n = 153). RESULTS: Bedtimes, wake times, and sleep duration remained relatively stable across the first 8 weeks of treatment. Sleep duration and fatigue were not related for the entire sample, though children's self-reported sleep duration was positively correlated with fatigue only at the baseline time point. Parent reports of fatigue significantly decreased for leukemia patients but remained rather high for solid tumor and brain tumor patients. CONCLUSIONS: Because fatigue remained high for solid tumor and brain tumor patients across the initial 8 weeks of treatment, this may highlight the need for intervention in this patient population. PMID- 25112563 TI - A multicentre, prospective, randomized, controlled study to evaluate the use of a fibrin sealant as an adjunct to sutured dural repair. AB - Background. Obtaining intra-operative watertight closure of the dura is considered important in reducing post-operative cerebrospinal fluid (CSF) leak. The purpose of this study was to evaluate a fibrin sealant as an adjunct to sutured dural repair to obtain intra-operative watertight closure in cranial neurosurgery. Methods. This randomized, controlled multicenter study compared a fibrin sealant (EVICEL(r) Fibrin Sealant [Human]) to sutured dural closure (Control). Subjects underwent supratentorial or posterior fossa procedures. Following primary dural repair by sutures, the closure was evaluated for intra operative CSF leak by moderately increasing the intracranial pressure. If present, subjects were randomized to EVICEL(r) or additional sutures (2:1 ratio), stratified by surgical approach. Following treatment, subjects were successful if no CSF leaks were present during provocative challenge. Safety was assessed to 30 days post-surgery, including incidence of CSF leakage. Results. One hundred and thirty-nine subjects were randomized: 89 to EVICEL(r) and 50 to Control. Intra operative watertight closure was achieved in 92.1% EVICEL(r)-treated subjects versus 38.0% controls; a treatment difference of 54.1% (p < 0.001). The treatment differences in the supratentorial and posterior fossa strata were 49.1% and 75.7%, respectively (p < 0.001). The incidence of adverse events was similar between treatment groups. No deaths or unexpected serious adverse drug reactions were reported. CSF leakage within 30 days post-operatively was 2.2% and 2.0% in EVICEL(r) and control groups, respectively. In addition, 2 cases of CSF rhinorrhoea were observed in the EVICEL(r) group. Although not associated with the suture line where EVICEL(r) was applied, when combined with the other CSF leaks, the observed leak rate in the EVICEL(r) group was 4.5%. Conclusions. These results indicate that EVICEL(r) is effective as an adjunct to dural sutures to provide watertight closure of the dura mater in cranial surgery. The study confirmed the safety profile of EVICEL(r). PMID- 25112562 TI - The relationship between nutritional status, inflammatory markers and survival in patients with advanced cancer: a prospective cohort study. AB - BACKGROUND: Malnutrition and elevated inflammatory markers have a negative impact on clinical outcomes in cancer patients. Few studies have investigated the associations between inflammatory makers, nutritional status and survival. This study investigates the association between nutritional status, inflammatory markers and overall survival (OS) in patients with advanced cancer. METHODS: This prospective cohort study recruited 114 adult patients from January 2007 to January 2010. It included patients diagnosed with advanced cancer, good Eastern Cooperative Oncology Group (ECOG) performance status 0-2, a prognosis of more than 3 months and had not received chemotherapy for advanced cancer prior to enrollment. Baseline data were collected prior to commencement of chemotherapy. Patients were followed up from the date of baseline nutritional assessment until the date of death or the date that data were last updated, whichever came first. RESULTS: Malnourished cancer patients had statistically significant higher concentrations of serum C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) or modified Glasgow Prognostic Score (mGPS) prior to starting chemotherapy. In univariate analyses to predict survival, mGPS 1 or 2 had a hazard ratio (HR) of 1.81 (95 % confidence interval (CI) 1.13-2.89) and NLR >= 5 had a HR of 1.13 (95 % CI 1.08-4.60) and malnutrition (HR of 1.66 for Patient-Generated Subjective Global Assessment (PG-SGA) B (95 % CI 1.02-2.71), and HR for severely malnourished patients (PG-SGA C) was 2.73 (95 % CI 1.50-4.96). CONCLUSIONS: Inflammatory markers were statistically associated with malnutrition. Malnutrition and mGPS were significant independent predictors of overall survival in patients with advanced cancer. PMID- 25112561 TI - Incidence and predictors of anticipatory nausea and vomiting in Asia Pacific clinical practice--a longitudinal analysis. AB - PURPOSE: Some patients experience nausea and/or vomiting (NV) before receipt of chemotherapy. Our objective was to evaluate the impact of prior chemotherapy induced NV (CINV) on the incidence of anticipatory NV in later cycles. METHODS: This multicenter, prospective non-interventional study enrolled chemotherapy naive adults scheduled to receive highly or moderately emetogenic chemotherapy (HEC/MEC) for cancer in six Asia Pacific countries, excluding those with emesis within 24 h before cycle 1 chemotherapy. On day 1 before chemotherapy, patients answered four questions regarding emesis in the past 24 h, nausea, expectation of post-chemotherapy nausea, and anxiety in the past 24 h, the latter three scored from 0-10 (none-maximum). Multivariate logistic regression was used to assess the impact of prior CINV on anticipatory NV in cycles 2 and 3. RESULTS: Five hundred ninety-eight patients (59% female) were evaluable in cycle 2 (49% HEC, 51% MEC). The incidence of anticipatory emesis was low before cycles 2 and 3 (1.5-2.3%). The incidence of clinically significant anticipatory nausea (score of >=3) was 4.8, 7.9, and 8.3% before cycles 1, 2, and 3, respectively, with adjusted odds ratio (OR), 3.95 (95% confidence interval (CI), 2.23-7.00; p < 0.001) for patients with clinically significant nausea in prior cycles, compared with none. The adjusted ORs for other anticipatory NV endpoints ranged from 4.54-4.74 for patients with prior CINV. The occurrence of clinically significant anxiety in the prior cycle also resulted in a significantly increased likelihood of anticipatory nausea. CONCLUSIONS: These findings highlight the importance of preventing CINV in cycle 1 to reduce anticipatory NV in subsequent cycles. PMID- 25112564 TI - The general and mental health of movers to more- and less-disadvantaged socio economic and physical environments within the UK. AB - Residential mobility may play an important role in influencing both individual health, by determining individual exposures to environments, and area health, by shaping area population composition. This study is the first analysis of migration within the UK to compare general and mental health among adults by age group and consider moves between neighbourhoods with different levels of both socio-economic and physical environment disadvantage. The analysis assesses 122,570 cases from the annual British Household Panel Survey, 1996-2006, based upon pooled data describing moves between consecutive waves of the survey. It assesses the rates and binary logistic regression model odds of self-reported general health and mental health problems of movers and stayers by age group. It also compares movers between Census Area Statistics wards in the UK with different levels of Carstairs and Multiple Environmental Deprivation Index (MEDIx) scores. At all ages, movers had similar or higher odds of poor general and mental health relative to non-movers. Risk of mental health problems were particularly elevated among movers and remained significant after adjustment for socio-demographic variables in most age groups. In adjusted analysis of all adults odds of poor general and mental health were most elevated among movers to more socio-economically deprived areas, with the highest odds for mental health (1.54 95% CI 1.27-1.86). In contrast, risk of poor mental health among total adults was greatest among movers to better physical environments (1.40 95% CI 1.16-1.70). This study therefore finds little evidence of 'healthy migrant effects' among recent movers within the UK and suggests movers have particularly elevated risk of mental health problems. It also indicates that selective migration may not contribute to poor health found in UK neighbourhoods with multiple physical environment deprivation. Further analysis should explore why people with mental health problems are more likely to move to socio-economically deprived neighbourhoods. PMID- 25112565 TI - How does mental-physical multimorbidity express itself in lived time and space? A phenomenological analysis of encounters with depression and chronic physical illness. AB - Mental-physical multimorbidity (the co-existence of mental and physical ill health) is highly prevalent and associated with significant impairments and high healthcare costs. While the sociology of chronic illness has developed a mature discourse on coping with long term physical illness the impact of mental and physical health have remained analytically separated, highlighting the need for a better understanding of the day-to-day complexities encountered by people living with mental-physical multimorbidity. We used the phenomenological paradigm of the lived body to elucidate how the experience of mental-physical multimorbidity shapes people's lifeworlds. Nineteen people with chronic obstructive pulmonary disease (COPD) and depression (defined as a score >=8 on depression scale of Hospital Anxiety and Depression Scale) were recruited from secondary NHS care and interviewed at their homes. Data were analysed phenomenologically using van Manen's lifeworld existential framework of the lived body, lived time, lived space, lived relations. Additionally, we re-analysed data (using the same framework) collected from 13 people recruited from secondary NHS care with either COPD, rheumatoid arthritis, heart disease, or type 1 or type 2 diabetes and depression. The phenomenology of mental-physical multimorbidity was articulated through embodied and emotional encounters with day-to-day life in four ways: [a] participants' perception of lived time and lived space contracted; [b] time and [c] space were experienced as liminal categories, enforcing negative mood and temporal and spatial contraction; and [d] time and space could also be customised to reinstate agency and self-determination. Mental-physical multimorbidity negatively impacts on individuals' perceptions of lived time and lived space, leading to a loss of agency, heightened uncertainty, and poor well-being. Harnessing people's capacity to modify their experience of time and space may be a novel way to support people with mental-physical multimorbidity to live well with illness. PMID- 25112566 TI - Fragile health and fragile wealth: mortgage strain among African American homeowners. AB - Several recent studies identify illness and disability as contributors to mortgage strain, suggesting that the disproportionate burden of poor health that African Americans experience may be an important source of housing fragility in this population. In order to understand how poor health plays out in the lived experiences of African-American homeowners and contributes to mortgage strain, we present an analysis of 28 in-depth interviews conducted with middle and working class African-American homeowners at risk of losing their homes. Our interviews show how racial inequalities in health, which result from an ongoing history of racial discrimination, intersect with other racially stratified sources of housing fragility to put homeowners at risk of foreclosure. Many participants in this study were long-term homeowners who experienced mortgage strain as result of a health-related event that triggered the collapse of a fragile household budget. Like many middle and working-class African Americans, participants experienced poor health and disability at relatively young ages. Additionally, they often lacked access to personal and public safety nets that could buffer the consequences of illness. Understanding how poor health contributes to mortgage strain among African-American homeowners provides important insight into the downstream consequences of health inequalities. Furthermore, understanding the processes through which illness can act as a financial shock has important policy implications. PMID- 25112567 TI - Modeling satisfaction amongst the elderly in different Chinese urban neighborhoods. AB - Rapidly aging populations constitute a critical issue for researchers and policymakers across the world; the challenges of a shifting demographic structure are particularly pertinent in the case of China. Population control strategies implemented in China in the late 1970s have substantially changed the social and demographic structure of Chinese cities and the traditional role of families in caring for elderly people. To meet the growing needs of elderly residents "aging in place," age-friendly environments and new types of senior services are required and encouraged. This research examines the satisfaction of seniors in relation to the elderly services and living environments available to them, through empirical studies of six types of neighborhoods in Beijing. Using structural equation modeling (SEM), a satisfaction model under the Person Environment Fit (P-E Fit) model framework was developed. This model considered the senior respondent's health status, economic attributes, family and social support networks, and neighborhood living environments. Social support was found to be the primary factor affecting satisfaction amongst the urban elderly in Beijing. The research also highlights the need to differentiate between different types of neighborhoods, which can differ significantly in terms of the socio economic attributes (i.e., family structure, income, and education) of their senior residents. As such, based on the path coefficients revealed by different structural equation models of various neighborhoods, four types of neighborhoods were identified: in Type 1 neighborhoods, the neighborhood environment and the senior services provided by communities were primary factors in elderly satisfaction; in Type 2 neighborhoods, the satisfaction of inhabitants was strongly influenced by personal attributes such as health and income; Type 3 neighborhoods were residence of low-income people where the level of social support was the foremost factor; and in Type 4, social support and the environment were both essential. PMID- 25112568 TI - Predictors of suicides occurring within suicide clusters in Australia, 2004-2008. AB - A number of studies have investigated the presence of suicide clusters, but few have sought to identify risk and protective factors of a suicide occurring within a cluster. We aimed to identify socio-demographic and contextual characteristics of suicide clusters from national and regional analyses of suicide clusters. We searched the National Coroners Information System for all suicides in Australia from 2004 to 2008. Scan statistics were initially used to identify those deaths occurring within a spatial-temporal suicide cluster during the period. We then used logistic regression and generalized estimation equations to estimate the odds of each suicide occurring within a cluster differed by sex, age, marital status, employment status, Indigenous status, method of suicide and location. We identified 258 suicides out of 10,176 suicides during the period that we classified as being within a suicide cluster. When the deceased was Indigenous, living outside a capital city, or living in the northern part of Australia (in particular, Northern Territory, Queensland and Western Australia) then there was an increased likelihood of their death occurring within a suicide cluster. These findings suggest that suicide clustering might be linked with geographical and Indigenous factors, which supported sociological explanations of suicide clustering. This finding is significant for justifying resource allocation for tackling suicide clustering in particular areas. PMID- 25112569 TI - Social status and biological dysregulation: the "status syndrome" and allostatic load. AB - Data from a national sample of 1255 adults who were part of the MIDUS (Mid-life in the U.S.) follow-up study and agreed to participate in a clinic-based in-depth assessment of their health status were used to test the hypothesis that, quite part from income or educational status, perceptions of lower achieved rank relative to others and of relative inequality in key life domains would be associated with greater evidence of biological health risks (i.e., higher allostatic load). Results indicate that over a variety of status indices (including, for example, the person's sense of control, placement in the community rank hierarchy, perception of inequality in the workplace) a syndrome of perceived relative deprivation is associated with higher levels of biological dysregulation. The evidence is interpreted in light of the well-established associations between lower socio-economic status and various clinically identified health morbidities. The present evidence serves, in effect, both as a part of the explanation of how socio-economic disparities produce downstream morbidity, and as an early warning system regarding the ultimate health effects of currently increasing status inequalities. PMID- 25112570 TI - Serum-induced neurite retraction in CAD cells--involvement of an ATP-actin retractile system and the lack of microtubule-associated proteins. AB - Cultured catecholamine-differentiated cells [which lack the microtubule associated proteins (MAPs): MAP1B, MAP2, Tau, STOP, and Doublecortin] proliferate in the presence of fetal bovine serum, and, in its absence, cease dividing and generate processes similar to the neurites of normal neurons. The reintroduction of serum induces neurite retraction, and proliferation resumes. The neurite retraction process in catecholamine-differentiated cells was partially characterized in this study. Microtubules in the cells were found to be in a highly dynamic state, and tubulin in the microtubules consisted primarily of the tyrosinated and deacetylated isotypes. Increased levels of acetylated or Delta2 tubulin (which are normally absent) did not prevent serum-induced neurite retraction. Treatment of differentiated cells with lysophosphatidic acid or adenosine deaminase induced neurite retraction. Inhibition of Rho-associated protein kinase, ATP depletion and microfilament disruption each (individually) blocked serum-induced neurite retraction, suggesting that an ATP-dependent actomyosin system underlies the mechanism of neurite retraction. Nocodazole treatment induced neurite retraction, but this effect was blocked by pretreatment with the microtubule-stabilizing drug paclitaxel (Taxol). Paclitaxel did not prevent serum-induced or lysophosphatidic acid-induced retraction, suggesting that integrity of microtubules (despite their dynamic state) is necessary to maintain neurite elongation, and that paclitaxel-induced stabilization alone is not sufficient to resist the retraction force induced by serum. Transfection with green fluorescent protein-Tau conferred resistance to retraction caused by serum. We hypothesize that, in normal neurons (cultured or in vivo), MAPs are necessary not only to stabilize microtubules, but also to establish interactions with other cytoskeletal or membrane components to form a stable structure capable of resisting the retraction force. PMID- 25112571 TI - Functionalized graphene as a nanostructured membrane for removal of copper and mercury from aqueous solution: a molecular dynamics simulation study. AB - The purpose of the present study was to investigate the removal of copper and mercury using functionalized graphene as a nanostructured membrane. The molecular dynamics simulation method was used to investigate the removal ability of these ions from aqueous solution using functionalized graphene membrane. The studied systems included a functionalized graphene membrane which was placed in the aqueous ionic solution of CuCl2 and HgCl2. An external electrical field was applied along the z axis of the system. The results indicated that the application of electrical field on the system caused the desired ions to pass through the functionalized graphene membrane. The Fluorinated pore (F-pore) terminated graphene selectively conducted Cu(2+) and Hg(2+) ions. The calculation of the potential of mean force of ions revealed that Cu(2+) and Hg(2+) ions face a relatively small energy barrier and could not pass through the F-pore graphene unless an external electrical field was applied upon them. In contrast, the energy barrier for the Cl(-) ion was large and it could not pass through the F pore graphene. The findings of the study indicate that the permeation of ions across the graphene was a function of applied electrical fields. The findings of the present study are based on the detailed analysis and consideration of potential of mean force and radial distribution function curves. PMID- 25112572 TI - India must act to stem rise of unnecessary medical interventions, says World Bank. PMID- 25112573 TI - Elevated prenatal methylmercury exposure in Nigeria: evidence from maternal and cord blood. AB - Methylmercury is a neurodevelopmental toxicant that is globally distributed though little is known about prenatal exposures in sub-Saharan Africa. The objective of the current study was to measure total mercury levels in cord blood and maternal blood from 95 mother-newborn pairs recruited from hospitals in Nnewi, Nigeria. The secondary aims of the study were to explore if demographic and dietary factors were associated with blood mercury levels, and to explore if mercury levels were associated with any self-reported health outcome and childbirth outcome. Maternal blood mercury levels averaged 3.6 MUg L(-1) and ranged from 1.1 MUg L(-1) to 9.5 MUg L(-1). Cord blood mercury averaged 5.1 MUg L(-1) and ranged from 1.2 MUg L(-1) to 10.6 MUg L(-1). The mean ratio of mercury in paired cord blood to maternal blood was 1.5 and it ranged from 0.4 to 3.2. Mercury in maternal and cord blood were significantly correlated (r=0.471). More than one-third of mothers reported eating fish at least once per day, and a weak (p=0.08) fish consumption-related increase in blood mercury was found. Cord blood mercury was positively and significantly associated with birth weight and length, and head and chest circumference. Mercury levels in 36% of the participants exceeded the biomonitoring guideline associated with the United States Environmental Protection Agency (U.S. EPA) reference dose for mercury. The study shows that pregnant women and their newborns are exposed to methylmercury and that their exposures are higher compared to general populations sampled from other regions of the world. PMID- 25112574 TI - Sensitivity of the sea snail Gibbula umbilicalis to mercury exposure--linking endpoints from different biological organization levels. AB - Mercury contamination is a common phenomenon in the marine environment and for this reason it is important to develop cost-effective and relevant tools to assess its toxic effects on a number of different species. To evaluate the possible effects of Hg in the sea snail Gibbula umbilicalis, animals were exposed to increasing concentrations of the contaminant in the ionic form for 96 h. After this exposure period, mortality, feeding and flipping behavior, the activity of the biomarkers glutathione S-transferase, superoxide dismutase, catalase, lactate dehydrogenase and cholinesterase, the levels of lipid peroxidation and cellular energy allocation were measured. After 96 h of exposure to the highest Hg concentration (~LC20), there was a significant inhibition of the cholinesterase activity as well as impairment in the flipping behavior and post-exposure feeding of the snails. Cholinesterase inhibition was correlated with the impairment of behavioral responses also caused by exposure to Hg. These endpoints, including the novel flipping test, revealed sensitivity to Hg and might be used as relevant early warning indicators of prospective effects at higher biological organization levels, making these parameters potential tools for environmental risk assessment. The proposed test species showed sensitivity to Hg and proved to be a suitable and resourceful species to be used in ecotoxicological testing to assess effects of other contaminants in marine ecosystems. PMID- 25112575 TI - Effects of molecular weight on the diffusion coefficient of aquatic dissolved organic matter and humic substances. AB - In situ measurements of labile metal species using diffusive gradients in thin films (DGT) passive samplers are based on the diffusion rates of individual species. Although most studies have dealt with chemically isolated humic substances, the diffusion of dissolved organic matter (DOM) across the hydrogel is not well understood. In this study, the diffusion coefficient (D) and molecular weight (MW) of 11 aquatic DOM and 4 humic substances (HS) were determined. Natural, unaltered aquatic DOM was capable of diffusing across the diffusive gel membrane with D values ranging from 2.48*10(-6) to 5.31*10(-6) cm(2) s(-1). Humic substances had diffusion coefficient values ranging from 3.48*10(-6) to 6.05*10(-6) cm(2) s(-1), congruent with previous studies. Molecular weight of aquatic DOM and HS samples (~500-1750 Da) measured using asymmetrical flow field-flow fractionation (AF4) strongly influenced D, with larger molecular weight DOM having lower D values. No noticeable changes in DOM size properties were observed during the diffusion process, suggesting that DOM remains intact following diffusion across the diffusive gel. The influence of molecular weight on DOM mobility will assist in further understanding and development of the DGT technique and the uptake and mobility of contaminants associated with DOM in aquatic environments. PMID- 25112576 TI - Long-term manure application effects on phosphorus speciation, kinetics and distribution in highly weathered agricultural soils. AB - Phosphorus (P) K-edge XANES and Fe K-edge EXAFS spectroscopies along with sequential P chemical fractionation and desorption kinetics experiments, were employed to provide micro- and macro-scale information on the long-term fate of manure application on the solid-state speciation, kinetics and distribution of P in highly weathered agricultural soils of southern Brazil. Soil test P values ranged from 7.3 up to 16.5 times as much higher than the reference soil. A sharp increase in amorphous Fe and Al amounts were observed as an effect of the consecutive application of manures. Whereas our results showed that the P sorption capacity of some manured soils was not significantly affected, P risk assessment indices indicated that P losses should be expected, likely due to the excessive manure rates applied to the soils. The much higher contents of amorphous Fe and Al (hydr)oxides (55% and 80% increase with respect to the reference soil, respectively) in manured soils seem to have counterbalanced the inhibiting effect of soil organic matter on P sorption by creating additional P sorption sites. Accordingly, the newly created P sorbing surfaces were important to prevent an even larger P loss potential. Phosphorus K-edge XANES lent complimentary hints on the loss of crystallinity and transformation of originally present Fe-P minerals into poorly crystalline ones as an effect of manuring, whereas Fe K-edge EXAFS provided insights into the structural changes underwent in the soils upon manure application and soil management. PMID- 25112577 TI - Monitoring bisphenol A and its biodegradation in water using a fluorescent molecularly imprinted chemosensor. AB - In this paper, we present a simple and rapid method for monitoring bisphenol A (BPA) and its biodegradation in environmental water using a fluorescent molecularly imprinted polymer chemosensor (fMIPcs). A fluorescent molecularly imprinted polymer (fMIP) was first synthesized by precipitation polymerization method using BPA as template, dansyl methacrylate as functional monomer. Then a fMIPcs was constructed by combining the fMIP with a fluorescent microplate reader. The fMIPcs displayed selective, concentration-dependent fluorescence quenching in response to BPA in water even in the existence of interferences, thereby allowing reliable high through-put quantification of BPA via simple fluorescence measurements. The fMIPcs was able to directly quantify BPA (from 10 to 2000 MUg L(-1)) in different environmental water samples (distilled water, distilled water containing heavy metals and humic acid, tap water, and river water) with high accuracy, and to monitor BPA biodegradation in real-time. Using the fMIPcs, it was possible to achieve fast analytical results with lower limit of detection for BPA (3 MUg L(-1)) from smaller sample volume (250 MUL), which are superior to many relevant methods reported in the literature. Moreover, BPA levels and biodegradation rates measured by fMIPcs are comparable to the instrument-based method (HPLC). The fMIPcs developed in this work offers a new solution for simple, rapid, accurate and high through-put BPA quantification, and makes it possible to monitor BPA biodegradation in real time. PMID- 25112578 TI - Transport via xylem and accumulation of aflatoxin in seeds of groundnut plant. AB - Aflatoxin contamination in groundnut seeds in the absence of any aflatoxigenic fungi leads to a hypothesis that aflatoxins are present naturally in soil and is transferred to seeds through uptake by roots. A survey was conducted on the natural occurrence of aflatoxins in agricultural soils, among nine main groundnut growing regions of Karnataka state, India. All 71 soil samples collected in this survey were contaminated with aflatoxins esp. AFB1. An in vitro xylem sap experiment proved the ability of groundnut plant roots to absorb AFB1, and transport to aerial plant parts via the xylem. Hydroponics experiment also proved the uptake of AFB1 by the roots and their translocation to shoot. Uptake was affected by the initial concentration of toxin and pH of the medium. Among the 14 varieties screened, GPBD4 and MLT.K.107 (III) recorded highest and least AFB1 uptake, respectively. The above results were validated using a greenhouse experiment. Here, the aflatoxin absorbed by root gradually transferred to shoot that was later found in seeds towards the end of experiment. Thus, the groundnut seeds can also get contaminated with aflatoxin by direct uptake of aflatoxin through conducting tissue in addition to fungal infection. The present study revealed the novel mode of aflatoxin contamination in groundnut seeds without fungal infection. PMID- 25112579 TI - Characteristics and sources of atmospheric mercury speciation in a coastal city, Xiamen, China. AB - Semi-continental monitoring of gaseous elemental mercury (GEM), particulate mercury (Hgp), and reactive gaseous mercury (RGM) was conducted in the Institute of Urban Environment, CAS in Xiamen, China from March 2012 to February 2013. The average concentrations and relative standard deviations (RSD) were 3.50 (34.6%) ng m(-3), 174.41 (160.9%) pg m(-3), and 61.05 (113.7%) pg m(-3) for GEM, Hgp, and RGM, respectively. The higher concentrations of GEM and Hgp were observed in spring and winter months, indicating the combustion source, while RGM showed the different seasonal variation with highest concentration in spring and the minimum value in winter. The concentrations of Hg species were generally elevated in nighttime and low in daytime to reflect the diurnal changes in meteorology, especially the mixing condition of the air masses. The high Hg concentrations were observed in SWW-NW sectors due to calm wind while the low levels in NE-SE due to high speed wind, and the amplitude was much larger for Hgp and RGM. Backward trajectories calculation indicated that summer air masses were much more from ocean with lower Hg while the air masses were mainly from inland area in other seasons. Principal component analysis suggested that combustion and road traffic emissions were the dominant anthropogenic mercury sources for the study area, and the temporal distribution of atmospheric mercury was mainly the result of climatological change. PMID- 25112580 TI - Use of multiple regression models to evaluate the formation of halonitromethane via chlorination/chloramination of water from Tai Lake and the Qiantang River, China. AB - The deterioration of water quality, especially organic pollution in Tai Lake and the Qiantang River, have recently received attention in China. The objectives of this study were to evaluate the formation of halonitromethanes (HNMs) using multiple regression models for chlorination and chloramination and to identify the key factors that influence the formation of HNMs in Tai Lake and the Qiantang River. The results showed that the total formation of HNMs (T-HNMs) during chlorination and chloramination could be described using the following models: (1) [Formula: see text] =(10)(5.267)(DON)(6.645)(Br(-))(0.737)(DOC)( )(5.537)(Cl2)(0.333)(t)(0.165) (R(2)=0.974, p<0.01, n=33), and (2) T HNMNH2Cl=(10)(-)(2.481)(Cl2)(0.451)(NO2(-))(0.382)(Br( ))(0.630)(t)(0.640)(Temp)(0.581) (R(2)=0.961, p<0.05, n=33), respectively. The key factors that influenced the T-HNM yields during chlorination were dissolved organic nitrogen (DON), bromide and dissolved organic carbon (DOC). The nitrite and bromide concentrations and the reaction time mainly affected the T-HNM yields during chloramination. Additional analysis indicated that the bromine incorporation factors (BIFs) for trihalogenated HNMs generally decreased as the chlorine/chloramine dose, temperature and reaction time decreased and increased as the bromide concentration increased. PMID- 25112581 TI - A colorimetric DET technique for the high-resolution measurement of two dimensional alkalinity distributions in sediment porewaters. AB - Measurements of porewater alkalinity are fundamental to the study of organic matter mineralization in sediments, which plays an essential role in the global cycles of carbon and nutrients. A new colorimetric diffusive equilibration in thin film (DET) technique is described for measuring two-dimensional total alkalinity distributions in sediment porewaters at high resolution (1-2 mm(2)). Thin polyacrylamide hydrogel layers (0.8 mm) equilibrate with the porewater and, after removal, are immediately laid onto another hydrogel containing formic acid, which reacts with alkalinity-generating species, and the pH-indicator bromophenol blue. The resultant color change is quantified using computer-imaging densitometry. The lower limit of detection is 0.2 meq L(-1) and the upper measurement limit is 8 meq L(-1). Deployment in seagrass colonized sediment revealed high levels of spatial heterogeneity in the porewater alkalinity distribution, with concentrations ranging from 2.28 meq L(-1) in the overlying water to 5.13 meq L(-1) in some parts of the sediment. This is the first time that two-dimensional, high-resolution distributions of porewater alkalinity have been measured. PMID- 25112583 TI - Introduction. Fertilization and early development. PMID- 25112582 TI - Avian feathers as a non-destructive bio-monitoring tool of trace metals signatures: a case study from severely contaminated areas. AB - The concentrations of trace metals were assessed using feathers of cattle egrets (Bubulcus ibis), collected within two industrial areas of Pakistan, Lahore and Sialkot. We found, in order of descending concentration: Zinc (Zn), Iron (Fe), Nickel (Ni), Copper (Cu), Cadmium (Cd), and Manganese (Mn), Chromium (Cr), Arsenic (As), and Lithium (Li), without any significant difference (except Fe, Zn, and Ni) between the two areas. The concentrations of trace metals, we recorded were among the highest ever reported in the feathers of avian species worldwide. The concentrations of Cr, Pb, Cd were above the threshold that affects bird reproductive success. The high contamination by heavy metals in the two areas is due to anthropogenic activities as well to natural ones (for As and Fe). The bioaccumulation ratios in eggs and feathers of the cattle egret, their prey, and the sediments from their foraging habitats, confirmed that avian feathers are a convenient and non-destructive sampling tool for the metal contamination. The results of this study will contribute to the environmental management of the Lahore and Sialkot industrial areas. PMID- 25112585 TI - Guided imagery for postoperative pain, energy healing for quality of life, probiotics for acute diarrhea in children, acupuncture for postoperative nausea and vomiting, and animal-assisted therapy for mental disorders. PMID- 25112584 TI - Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation. AB - BACKGROUND: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. AIM: To evaluate the long-term safety and tolerability of naloxegol, an oral, peripherally acting MU-opioid receptor antagonist (PAMORA), in patients with noncancer pain and OIC. METHODS: A 52-week, multicenter, open label, randomised, parallel-group phase 3 study was conducted in out-patients taking 30-1000 morphine-equivalent units per day for >=4 weeks. Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual-care (UC; investigator chosen laxative regimen) treatment for OIC. RESULTS: The safety set comprised 804 patients (naloxegol, n = 534; UC, n = 270). Mean exposure duration was 268 days with naloxegol and 297 days with UC. Frequency of adverse events (AEs) was 81.8% with naloxegol and 72.2% with UC. Treatment-emergent AEs occurring more frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 3.3%), diarrhoea (12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), flatulence (6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most naloxegol-emergent gastrointestinal AEs occurred early, resolving during or after naloxegol discontinuation and were mild or moderate in severity; 11 patients discontinued due to diarrhoea and nine patients owing to abdominal pain. Pain scores and mean daily opioid doses remained stable throughout the study; no attributable opioid withdrawal AEs were observed. Two patients in each group had an adjudicated major adverse cardiovascular event unrelated to study drug; no AEs were reported nor adjudicated as bowel perforations. CONCLUSION: In patients with noncancer pain and opioid-induced constipation, naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated. PMID- 25112586 TI - Predicting invasive breast cancer versus DCIS in different age groups. AB - BACKGROUND: Increasing focus on potentially unnecessary diagnosis and treatment of certain breast cancers prompted our investigation of whether clinical and mammographic features predictive of invasive breast cancer versus ductal carcinoma in situ (DCIS) differ by age. METHODS: We analyzed 1,475 malignant breast biopsies, 1,063 invasive and 412 DCIS, from 35,871 prospectively collected consecutive diagnostic mammograms interpreted at University of California, San Francisco between 1/6/1997 and 6/29/2007. We constructed three logistic regression models to predict the probability of invasive cancer versus DCIS for the following groups: women >= 65 (older group), women 50-64 (middle age group), and women < 50 (younger group). We identified significant predictors and measured the performance in all models using area under the receiver operating characteristic curve (AUC). RESULTS: The models for older and the middle age groups performed significantly better than the model for younger group (AUC = 0.848 vs, 0.778; p = 0.049 and AUC = 0.851 vs, 0.778; p = 0.022, respectively). Palpability and principal mammographic finding were significant predictors in distinguishing invasive from DCIS in all age groups. Family history of breast cancer, mass shape and mass margins were significant positive predictors of invasive cancer in the older group whereas calcification distribution was a negative predictor of invasive cancer (i.e. predicted DCIS). In the middle age group--mass margins, and in the younger group--mass size were positive predictors of invasive cancer. CONCLUSIONS: Clinical and mammographic finding features predict invasive breast cancer versus DCIS better in older women than younger women. Specific predictive variables differ based on age. PMID- 25112588 TI - The relationship between urotensin II and its receptor and the clinicopathological parameters of breast cancer. AB - BACKGROUND: Urotensin II is a vasoactive polypeptide. It is known that some vasoactive polypeptides are produced and secreted by tumor cells, and act as a paracrine growth stimulant. The aim of this study was to examine the relationship between urotensin II and its receptor's messenger RNA expression in breast cancer. MATERIAL/METHODS: Fifty-nine women with breast cancer were included in this study. The median age was 48 years. The relationships between urotensin II and urotensin II receptor mRNA expressions, which were derived from fresh breast cancer tissues and adjacent normal breast tissues, and clinical and pathological parameters, were assessed. RESULTS: We found expressions of urotensin II mRNA and its receptor in 55 of 59 breast cancer tissues and in 55 of 59 normal breast tissues. We found a positive significant correlation between urotensin II and its receptor (p=0.001, r=0.632), and found a negative, but insignificant, correlation between urotensin II and age (p=0.038, r=-0.281). Urotensin II levels were higher in the premenopausal group compared to the postmenopausal group (p<0.05). The mean urotensin II receptor expression was higher in the premenopausal group (p<0.05) compared to the postmenopausal group, and its expression was also higher in the group without extra-nodal invasion compared to that of the group with extra-nodal invasion (p=0.001). Urotensin II levels were higher in the group without lymphatic invasion compared to the group with lymphatic invasion (p=0.048). CONCLUSIONS: This study is the first in the English medical literature to determine the urotensin II and its receptor mRNA expressions in breast cancer tissues. Consequently, urotensin II seems be associated with menopausal status, and extra-nodal and lymphatic invasion. PMID- 25112590 TI - Uterine morcellation at the time of hysterectomy: techniques, risks, and recommendations. AB - IMPORTANCE: Uterine leiomyomata or fibroids are the most common pelvic tumor experienced in women. A minimally invasive approach to hysterectomy has proven benefits of cosmesis, lower blood loss, less pain, decreased hospital stay, and faster recovery. The incidence of uterine morcellation, the process of making a uterine specimen smaller for purposes of removal via a minimally invasive approach, has increased for this reason. OBJECTIVE: We review the history, techniques, and direct and indirect risks described in the literature, recommendations for appropriate use, and how to counsel patients regarding this procedure. EVIDENCE ACQUISITION: A thorough search of PubMed for all current literature was performed. Techniques for morcellation were reviewed. We included studies that addressed the type and incidence of morcellator-associated risks including those addressing the incidence of leiomyosarcoma in patients with presumed uterine fibroids. RESULTS: We have summarized several techniques to aid the practitioner in performing morcellation procedures and the risks involved. We have summarized all of the current consensus statements regarding the recommendations for use of morcellation and the approach to proper counseling. CONCLUSIONS AND RELEVANCE: Morcellation is an effective method of specimen removal that can decrease the need for laparotomy in both benign and malignant conditions. Upon analysis of current data and consensus statements, when possible, morcellation should be performed within a contained environment to minimize any potential tumor spread in the event of an undiagnosed malignancy. Patients should be adequately counseled to make an informed decision regarding undergoing a morcellation procedure. Future methods for enclosed specimen extraction will hopefully change the future of morcellation. PMID- 25112553 TI - [Patient's care and management of dyslipidemia in type 2 diabetic patients in the clinical practice in Spain: The LIPEDIA study]. AB - INTRODUCTION: Treatment of atherogenic dyslipidemia (AD) in type 2 diabetes (DM2) should focus on the global control of dyslipidemia. The aim of this study was to determine how hospital (MSs) and primary care specialist (GPs) from Spain manage AD in DM2 during their daily practice. METHODS: An observational, cross sectional, multicentric study was conducted. Information about daily practice was obtained from 497 MSs and 872 GPs across Spain. RESULTS: 66% of MSs and 30.5% of GPs considered DM2 patients to be high-risk. Most consider the c-LDL targets based on European guidelines. The statins most widely used are atorvastatin and simvastatin. However both MSs and GPs considered rosuvastatin to be the most appropriate statin for these patients. 82% of MSs and 68% of GPs considered that >50% of their patients achieved the c-LDL target. The main reasons of not achieving this target were lack of treatment adherence and pressure from the administration. Seventy four percent of MSs reported that there are no common clinical protocols with GPs. CONCLUSIONS: The differences in the perception of the real cardiovascular risk of the patient, low use of more appropriate statins, lack of adherence and poor perception of real c-LDL control may contribute to the failure in achieving lipid targets in DM2. PMID- 25112591 TI - The surgical management of cervical cancer: an overview and literature review. AB - IMPORTANCE: Surgery has evolved into the standard therapy for nonbulky carcinoma of the cervix. The mainstay of surgical management is radical hysterectomy; however, less radical procedures have a small but important role in the management of cervical tumors. OBJECTIVE: Our objective was to discuss the literature behind the different procedures utilized in the management of cervical cancer, emphasizing the radical hysterectomy. In addition, we aimed to discuss ongoing trials looking at the utility of less radical surgeries as well as emerging technologies in the management of this disease. EVIDENCE ACQUISITION: We performed a PubMed literature search for articles in the English language that pertained to the topic of surgical techniques and their outcomes in the treatment of cervical cancer. RESULTS: The minimally invasive approaches to radical hysterectomy appear to reduce morbidity without affecting oncological outcomes, although further data are needed looking at long-term outcomes with the robotic platform. Trials are currently ongoing looking at the role of less radical surgery for patients with low-risk disease and the feasibility of sentinel lymph node mapping. CONCLUSIONS AND RELEVANCE: Radical hysterectomy with pelvic lymphadenectomy has evolved into the standard therapy for nonbulky disease, and there is a clear advantage in the use of minimally invasive techniques to perform these procedures. However, pending ongoing trials, less radical surgery in patients with low-risk invasive disease as well as sentinel lymph node mapping may emerge as standards of care in selected patients with cervical carcinoma. PMID- 25112589 TI - Summary of international guidelines for physical activity after pregnancy. AB - Postpartum physical activity can improve mood, maintain cardiorespiratory fitness, improve weight control, promote weight loss, and reduce depression and anxiety. This review summarizes current guidelines for postpartum physical activity worldwide. PubMed (MEDLINE) was searched for country-specific government and clinical guidelines on physical activity after pregnancy through the year 2013. Only the most recent guideline was included in the review. An abstraction form facilitated extraction of key details and helped to summarize results. Six guidelines were identified from 5 countries (Australia, Canada, Norway, United Kingdom, and United States). All guidelines were embedded within pregnancy related physical activity recommendations. All provided physical activity advice related to breastfeeding and 3 remarked about physical activity after cesarean delivery. Recommended physical activities mentioned in the guidelines included aerobic (3/6), pelvic floor exercise (3/6), strengthening (2/6), stretching (2/6), and walking (2/6). None of the guidelines discussed sedentary behavior. The guidelines that were identified lacked specificity for physical activity. Greater clarity in guidelines would be more useful to both practitioners and the women they serve. Postpartum physical activity guidelines have the potential to assist women to initiate or resume physical activity after childbirth so that they can transition to meeting recommended levels of physical activity. Health care providers have a critical role in encouraging women to be active at this time, and the availability of more explicit guidelines may assist them to routinely include physical activity advice in their postpartum care. PMID- 25112592 TI - To boldly go. PMID- 25112594 TI - Successful aging and subjective well-being among oldest-old adults. AB - PURPOSE OF THE STUDY: This research integrates successful aging and developmental adaptation models to empirically define the direct and indirect effects of 2 distal (i.e., education and past life experiences) and 5 proximal influences (i.e., physical functioning, cognitive functioning, physical health impairment, social resources, and perceived economic status) on subjective well-being. The proximal influences involved predictors outlined in most extant models of successful aging (e.g., Rowe & Kahn, 1998 [Rowe, J. W., & Kahn, R. L. (1998). Successful aging. New York: Pantheon Books.]). Our model extends such models by including distal impact as well as interactions between distal and proximal impacts. DESIGN AND METHODS: Data were obtained from 234 centenarians and 72 octogenarians in the Georgia Centenarian Study. Structural equation modeling was conducted with Mplus 6.1. RESULTS: Results showed significant direct effects of physical health impairment and social resources on positive aspects of subjective well-being among oldest-old adults. We also found significant indirect effects of cognitive functioning and education on positive affect among oldest-old adults. Social resources mediated the relationship between cognitive functioning and positive affect; and cognitive functioning and social resources mediated the relationship between education and positive affect. In addition, physical health impairment mediated the relationship between cognitive functioning and positive affect; and cognitive functioning and physical health impairment mediated the relationship between education and positive affect. IMPLICATIONS: Integrating 2 different models (i.e., successful aging and developmental adaptation) provided a comprehensive view of adaptation from a developmental perspective. PMID- 25112596 TI - Combination of material flow analysis and substance flow analysis: a powerful approach for decision support in waste management. AB - The novelty of this paper is the demonstration of the effectiveness of combining material flow analysis (MFA) with substance flow analysis (SFA) for decision making in waste management. Both MFA and SFA are based on the mass balance principle. While MFA alone has been applied often for analysing material flows quantitatively and hence to determine the capacities of waste treatment processes, SFA is more demanding but instrumental in evaluating the performance of a waste management system regarding the goals "resource conservation" and "environmental protection". SFA focuses on the transformations of wastes during waste treatment: valuable as well as hazardous substances and their transformations are followed through the entire waste management system. A substance-based approach is required because the economic and environmental properties of the products of waste management - recycling goods, residues and emissions - are primarily determined by the content of specific precious or harmful substances. To support the case that MFA and SFA should be combined, a case study of waste management scenarios is presented. For three scenarios, total material flows are quantified by MFA, and the mass flows of six indicator substances (C, N, Cl, Cd, Pb, Hg) are determined by SFA. The combined results are compared to the status quo in view of fulfilling the goals of waste management. They clearly point out specific differences between the chosen scenarios, demonstrating potentials for improvement and the value of the combination of MFA/SFA for decision making in waste management. PMID- 25112595 TI - An agent-based simulation model for Clostridium difficile infection control. AB - BACKGROUND: Control of Clostridium difficile infection (CDI) is an increasingly difficult problem for health care institutions. There are commonly recommended strategies to combat CDI transmission, such as oral vancomycin for CDI treatment, increased hand hygiene with soap and water for health care workers, daily environmental disinfection of infected patient rooms, and contact isolation of diseased patients. However, the efficacy of these strategies, particularly for endemic CDI, has not been well studied. The objective of this research is to develop a valid, agent-based simulation model (ABM) to study C. difficile transmission and control in a midsized hospital. METHODS: We develop an ABM of a midsized hospital with agents such as patients, health care workers, and visitors. We model the natural progression of CDI in a patient using a Markov chain and the transmission of CDI through agent and environmental interactions. We derive input parameters from aggregate patient data from the 2007-2010 Wisconsin Hospital Association and published medical literature. We define a calibration process, which we use to estimate transition probabilities of the Markov model by comparing simulation results to benchmark values found in published literature. RESULTS: In a comparison of CDI control strategies implemented individually, routine bleach disinfection of CDI-positive patient rooms provides the largest reduction in nosocomial asymptomatic colonization (21.8%) and nosocomial CDIs (42.8%). Additionally, vancomycin treatment provides the largest reduction in relapse CDIs (41.9%), CDI-related mortalities (68.5%), and total patient length of stay (21.6%). CONCLUSION: We develop a generalized ABM for CDI control that can be customized and further expanded to specific institutions and/or scenarios. Additionally, we estimate transition probabilities for a Markov model of natural CDI progression in a patient through calibration. PMID- 25112597 TI - Transformation of membrane nanosurface of red blood cells under hemin action. AB - Hemin is the product of hemoglobin oxidation. Some diseases may lead to a formation of hemin. The accumulation of hemin causes destruction of red blood cells (RBC) membranes. In this study the process of development of topological defects of RBC membranes within the size range from nanoscale to microscale levels is shown. The formation of the grain-like structures in the membrane ("grains") with typical sizes of 120-200 nm was experimentally shown. The process of formation of "grains" was dependent on the hemin concentration and incubation time. The possible mechanism of membrane nanostructure alterations is proposed. The kinetic equations of formation and transformation of small and medium topological defects were analyzed. This research can be used to study the cell intoxication and analyze the action of various agents on RBC membranes. PMID- 25112598 TI - The association of dorsiflexion flexibility on knee kinematics and kinetics during a drop vertical jump in healthy female athletes. AB - PURPOSE: While previous studies have examined the association between ankle dorsiflexion flexibility and deleterious landing postures, it is not currently known how landing kinetics are influenced by ankle dorsiflexion flexibility. The purpose of this study was to examine whether ankle dorsiflexion flexibility was associated with landing kinematics and kinetics that have been shown to increase the risk of anterior cruciate ligament (ACL) injury in female athletes. METHODS: Twenty-three female collegiate soccer players participated in a preseason screening that included the assessment of ankle dorsiflexion flexibility and lower-body kinematics and kinetics during a drop vertical jump task. RESULTS: The results demonstrated that females with less ankle dorsiflexion flexibility exhibited greater peak knee abduction moments (r = -.442), greater peak knee abduction angles (r = .355), and less peak knee flexion angles (r = .385) during landing. The range of dorsiflexion flexibility for the current study was between 9 degrees and 23 degrees (mean = 15.0 degrees ; SD 3.9 degrees ). CONCLUSION: Dorsiflexion flexibility may serve as a useful clinical measure to predict poor landing postures and external forces that have been associated with increased knee injury risk. Rehabilitation specialists can provide interventions aimed at improving dorsiflexion flexibility in order to ameliorate the impact of this modifiable factor on deleterious landing kinematics and kinetics in female athletes. LEVEL OF EVIDENCE: II. PMID- 25112600 TI - Memory factors in Rey AVLT: Implications for early staging of cognitive decline. AB - Supraspan verbal list learning is widely used to assess dementia and related cognitive disorders where declarative memory deficits are a major clinical sign. While the overall learning rate is important for diagnosis, serial position patterns may give insight into more specific memory processes in patients with cognitive impairment. This study explored these patterns in a memory clinic clientele. One hundred eighty three participants took the Rey Auditory-Verbal Learning Test (RAVLT). The major groups were patients with Alzheimer's disease (AD), Vascular Dementia (VD), Mild Cognitive Impairment (MCI), and Subjective Cognitive Impairment (SCI) as well as healthy controls (HC). Raw scores for the five trials and five serial partitions were factor analysed. Three memory factors were found and interpreted as Primacy, Recency, and Resistance to Interference. AD and MCI patients had impaired scores in all factors. SCI patients were significantly impaired in the Resistance to Interference factor, and in the Recency factor at the first trial. The main conclusion is that serial position data from word list testing reflect specific memory capacities which vary with levels of cognitive impairment. PMID- 25112599 TI - Sensation seeking predicting growth in adolescent problem behaviors. AB - There is limited literature on the relationship between sensation seeking and adolescent risk behaviors, particularly among African Americans. We tested the association between psychometrically-derived subscales of the Zuckerman Sensation Seeking Scale and the intercepts and slopes of individual growth curves of conduct problems, sexual risk taking, and substance use from ages 13 to 18 years by sex. Boys and girls had different associations between sensation seeking and baseline levels and growth of risk behaviors. The Pleasure Seeking scale was associated with baseline levels of conduct problems in boys and girls, baseline substance use in boys, and growth in sexual risk taking and substance use by girls. Girls had the same pattern of associations with the Danger/Novelty scale as the Pleasure Seeking scale. Knowledge about the relationships between adolescent risk taking and sensation seeking can help in the targeted design of prevention and intervention programs for the understudied population of very low income, African American adolescents. PMID- 25112602 TI - Cartilage polysaccharide induces apoptosis in K562 cells through a reactive oxygen species-mediated caspase pathway. AB - In this study, a polysaccharide (PS) was successfully extracted from porcine cartilage and its effect on chronic myeloid leukemia was examined using human K562 cells. The results of cell proliferation assays indicated that the PS inhibited cancer cell growth at different concentrations. Morphological and biochemical changes characteristic of apoptosis were observed and confirmed by PI staining and TUNEL assay. The nuclear DNA, RNA and proteins of the cancer cells subjected to PS treatment were irreversibly destroyed by reactive oxygen species (ROS), additionally, the ROS effected on the cells directly. The apoptotic signals altered the permeability of the mitochondrial outer membrane, thereby resulted in the release of apoptotic factors into the cytoplasm that induced apoptosis. As caspase-3/7, 8 and 9 were expressed, it was speculated that both intrinsic and extrinsic pathways were involved in the PS-induced apoptosis. PMID- 25112603 TI - Prevalence of tonsillar human papillomavirus infections in Denmark. AB - The incidence of tonsillar carcinomas associated with Human Papillomavirus (HPV) infection has increased dramatically over the last three decades. In fact, currently in Scandinavia, HPV-associated cases account for over 80 % of tonsillar carcinoma cases. Yet, the epidemiology and natural history of tonsillar HPV infections remains poorly characterized. Our aim was to characterize such infections in the Danish population in tumor-free tonsillar tissue. Unlike previous studies, we considered both palatine tonsils. We examined both tonsils from 80 patients with peritonsillar abscess (n = 25) or chronic tonsillar disease (n = 55). HPV was detected by nested PCR with PGMY 09/11 and GP5+/GP6+L1 consensus primers, and typed by sequencing. Samples were also analyzed using a higher-throughput method, the CLART HPV 2 Clinical Array Assay. The overall prevalence of HPV tonsillar infection was 1.25 % (1/80, 95 % CI 0.03-6.77 %) by nested PCR, and 0 % by CLART HPV2 Clinical Array. The HPV-positive patient was a 16-year-old female with recurrent tonsillitis and tonsillar hypertrophy. The type detected was HPV6. HPV was not detected in the contralateral tonsil of this patient. Compared to cervical HPV infections in Denmark, tonsillar HPV infections are 10- to 15-fold less frequent. In the HPV-positive patient in this study, HPV was detected in only one of the tonsils. This raises the possibility that prior studies may underestimate the prevalence of HPV infections, as they do not consider both palatine tonsils. PMID- 25112606 TI - Connective tissue diseases: A mechanism of B cell hyperactivity in SLE. PMID- 25112607 TI - Metallogel template fabrication of pH-responsive copolymer nanowires loaded with silver nanoparticles and their photocatalytic degradation of methylene blue. AB - Poly(N,N'-methylenebisacrylamide-4-vinylpyridine) (P(MBA-4VP)) nanowires loaded with silver nanoparticles (Ag NPs) have been fabricated by silver metallogel template copolymerization, and subsequently, silver ions are reduced instead of the template being removed. Ag NPs with a diameter of 5-15 nm were dispersed throughout the core of P(MBA-4VP) nanowires. The size and distribution of the formed Ag NPs could be finely controlled by reduction time. The pH sensitivity of P(MBA-4VP) nanowires offers the possibility of Ag NP release from the nanowires under acidic conditions. The photocatalytic performance of the P(MBA-4VP) nanowires loaded with Ag NPs was evaluated for the degradation of methylene blue (MB) under UV light irradiation. Their rate of degradation is dependent on the content and size of the Ag NPs, as well as the pH values of the MB solution. Moreover, the P(MBA-4VP) nanowires loaded with Ag NPs exhibited high photostability, and the photocatalytic efficiency reduced by only 1.81% after being used three times. PMID- 25112608 TI - Evolution of an adenine-copper cluster to a highly porous cuboidal framework: solution-phase ripening and gas-adsorption properties. AB - The synthesis and directed evolution of a tetranuclear copper cluster, supported by 8-mercapto-N9-propyladenine ligand, to a highly porous three-dimensional cubic framework in the solid state is reported. The structure of this porous framework was unambiguously characterized by X-ray crystallography. The framework contains about 62 % solvent-accessible void; the presence of a free exocyclic amino group in the porous framework facilitates reversible adsorption of gas and solvent molecules. Oriented growth of framework in solution was also tracked by force and scanning electron microscopy studies, leading to identification of an intriguing ripening process, over a period of 30 days, which also revealed formation of cuboidal aggregates in solution. The elemental composition of these cuboidal aggregates was ascertained by EDAX analysis. PMID- 25112604 TI - Pharmacogenetics: can genes determine treatment efficacy and safety in JIA? AB - Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition in childhood, with many children requiring immunomodulatory therapies for many years following diagnosis. A considerable proportion of children experience therapeutic inefficacy or substantial adverse effects, or both, but a lack of reliable clinical indicators and biomarkers to predict treatment response prevents optimization of existing therapies. The identification of valid candidate gene variants involved in the pathways of methotrexate and etanercept, the most commonly used medications in JIA, has seen little success to date. The limited success of these studies is possibly due to the presence of confounding variables in the study populations, the heterogeneity of outcome parameters used to determine treatment response and the small number of candidate gene variants analysed. The first genome-wide pharmacogenetic study in JIA has identified gene regions of particular biological interest, but these findings require validation. Moreover, epigenetic mechanisms as well as ontogeny processes might be additional factors influencing drug responses. Access to large, well-documented JIA cohorts and the rapid development of advanced genome analytics is ushering in a personalized approach to treatment. The discovery of new pharmacogenomic biomarkers and systems pathways can provide new drug targets and predictive tools for improved drug response and fewer adverse drug reactions in JIA. PMID- 25112609 TI - Efficacy and safety of dipeptidyl peptidase-4 inhibitors as an add-on to insulin treatment in patients with Type 2 diabetes: a review. AB - AIM: To review and discuss the results from the clinical controlled trials comparing a dipeptidyl peptidase-4 inhibitor with placebo treatment as add-on to insulin treatment with respect to changes in HbA1c , weight, fasting plasma glucose, risk of hypoglycaemia and safety in patients with Type 2 diabetes. METHODS: We searched the MEDLINE and PubMed databases to identify all randomized controlled clinical trials evaluating dipeptidyl peptidase-4 inhibitors as an add on to insulin in patients with Type 2 diabetes, which were selected for review. The abstracts and posters of the recent annual meetings of the American Diabetes Association and European Association for the Study of Diabetes were hand searched, as were the reference lists of articles identified. RESULTS: Adding a dipeptidyl peptidase-4 inhibitor to insulin treatment resulted in a glucose lowering effect of ~ 6.6-8.7 mmol/mol (0.60-0.80%) from a baseline HbA1c of 67-78 mmol/mol (8.3-9.3%), without increasing the risk of hypoglycaemia. The dipeptidyl peptidase-4 inhibitor treatment had no effect on body weight or daily dose of insulin. The frequency and severity of adverse events did not differ between dipeptidyl peptidase-4 inhibitor and placebo treatment. CONCLUSION: Adding a dipeptidyl peptidase-4 inhibitor treatment to insulin has a moderate effect on HbA1c , a weight-neutral effect and a good safety profile. The risk of hypoglycaemia is not increased despite a significant improvement in HbA1c . PMID- 25112610 TI - Modifications to nano- and microstructural quality and the effects on mechanical integrity in Paget's disease of bone. AB - Paget's disease of bone (PDB) is the second most common bone disease mostly developing after 50 years of age at one or more localized skeletal sites; it is associated with severely high bone turnover, bone enlargement, bowing/deformity, cracking, and pain. Here, to specifically address the origins of the deteriorated mechanical integrity, we use a cohort of control and PDB human biopsies to investigate multiscale architectural and compositional modifications to the bone structure (ie, bone quality) and relate these changes to mechanical property measurements to provide further insight into the clinical manifestations (ie, deformities and bowing) and fracture risk caused by PDB. Here, at the level of the collagen and mineral (ie, nanometer-length scale), we find a 19% lower mineral content and lower carbonate-to-phosphate ratio in PDB, which accounts for the 14% lower stiffness and 19% lower hardness promoting plastic deformation in pathological bone. At the microstructural scale, trabecular regions are known to become densified, whereas cortical bone loses its characteristic parallel-aligned osteonal pattern, which is replaced with a mosaic of lamellar and woven bone. Although we find this loss of anisotropic alignment produces a straighter crack path in mechanically-loaded PDB cases, cortical fracture toughness appears to be maintained due to increased plastic deformation. Clearly, the altered quality of the bone structure in PDB affects the mechanical integrity leading to complications such as bowing, deformities, and stable cracks called fissure fractures associated with this disease. Although the lower mineralization and loss of aligned Haversian structures do produce a lower modulus tissue, which is susceptible to deformities, our results indicate that the higher levels of plasticity may compensate for the lost microstructural features and maintain the resistance to crack growth. PMID- 25112611 TI - Review of the hymenopteran fauna of New Caledonia with a checklist of species. AB - The hymenopteran fauna of New Caledonia is reviewed and compared with that of Australia and New Zealand, as well as other islands in the south-west Pacific. In conclusion, several different scenarios (e.g., recent dispersal events and radiations) can be used to explain the extant distribution of New Caledonian Hymenoptera. A detailed checklist of 409 species and subspecies of Hymenoptera of New Caledonia is provided, along with estimates of the undescribed fauna, and a summary of the general biology of the families represented in the region. PMID- 25112605 TI - Adverse reactions to biologic agents and their medical management. AB - Biologic agents have substantially advanced the treatment of immunological disorders, including chronic inflammatory and autoimmune diseases. However, these drugs are often associated with adverse events (AEs), including allergic, immunological and other unwanted reactions. AEs can affect almost any organ or system in the body and can occur immediately, within minutes to hours, or with a delay of several days or more after initiation of biologic therapy. Although some AEs are a direct consequence of the functional inhibition of biologic-agent targeted antigens, the pathogenesis of other AEs results from a drug-induced imbalance of the immune system, intermediary factors and cofactors, a complexity that complicates their prediction. Herein, we review the AEs associated with biologic therapy most relevant to rheumatic and immunological diseases, and discuss their underlying pathogenesis. We also include our recommendations for the medical management of such AEs. Increased understanding and improved risk management of AEs induced by biologic agents will enable better use of these versatile immune-response modifiers. PMID- 25112612 TI - Taxonomic revision of the ornate skink (Oligosoma ornatum; Reptilia: Scincidae) species complex from northern New Zealand. AB - Although the New Zealand skink fauna is known to be highly diverse, a substantial proportion of the recognised species remain undescribed. We completed a taxonomic revision of the ornate skink (Oligosoma ornatum (Gray, 1843)) as a previous molecular study indicated that it represented a species complex. As part of this work we have resolved some nomenclatural issues involving this species and a similar species, O. aeneum (Girard, 1857). A new skink species, Oligosoma roimata sp. nov., is described from the Poor Knights Islands, off the northeast coast of the North Island of New Zealand. This species is diagnosed by a range of morphological characters and genetic differentiation from O. ornatum. The conservation status of the new taxon appears to be of concern as it is endemic to the Poor Knights Islands and has rarely been seen over the past two decades. PMID- 25112613 TI - Description of Mitogoniella mucuri sp. nov. (Opiliones: Gonyleptidae) and considerations on polymorphic traits in the genus and Gonyleptidae. AB - Mitogoniella mucuri sp. nov. is described for some caves in Minas Gerais, Brazil. This species differs from other Mitogoniella species by large tubercles on the ocularium that have fused bases and free apices (or almost fully fused tubercles with bifurcated apices), and by a large dry-mark between tubercles on the longitudinal groove of area III. Mitogoniella species are hard to recognize: their males lack any armature on leg IV (normally an important diagnostic character among gonyleptid species), and they also present many polymorphisms in coloration (dry-mark), male secondary sex characters, the number of dorsal scutal granules, and the shapes of tubercles on the ocularium. The patterns of these polymorphisms are discussed for the genus and for the family. The present work also presents new occurrences for all the species of the genus, and their biogeography is discussed. PMID- 25112614 TI - A new species of the genus Pethia from Mizoram, northeastern India (Teleostei: Cyprinidae). AB - The paper describes Pethia expletiforis, a new cyprinid species from the Ka-ao River, Kaladan drainage, Mizoram, India. It is distinguished from its congeners in the Chindwin-Irrawaddy and Ganga-Brahmaputra drainages by the combination of: a complete lateral line, nine predorsal scales, 12 circumpeduncular scales, 1/24/1/31/2 transverse scales, a black blotch on the caudal peduncle, and the absence of a humeral mark and barbels. PMID- 25112615 TI - A new species of Hemiphyllodactylus (Reptilia: Gekkonidae) from northern Vietnam. AB - We describe a new species of the genus Hemiphyllodactylus on the basis of four specimens from Cao Bang Province, northern Vietnam. Hemiphyllodactylus zugi sp. nov. is distinguished from the remaining congeners by a combination of the following characters: a bisexual taxon; average SVL of adult males 41 mm, of adult female 46.6 mm; chin scales bordering mental and first infralabial distinctly enlarged; digital lamellae formulae 3-4-4-4 (forefoot) and 4-5-5-5 (hindfoot); femoral and precloacal pore series continuous, 18-21 in total in males, absent in female; cloacal spur single in males; dorsal trunk pattern of dark brown irregular transverse bands; dark lateral head stripe indistinct; upper zone of flank with a series of large light spots, edged above and below in dark grey; caecum and gonadal ducts unpigmented. PMID- 25112616 TI - Schillerosaurus gen. nov., a replacement name for the lizard genus Schilleria Evans and Chure, 1999 a junior homonym of Schilleria Dahl, 1907. PMID- 25112617 TI - Names and publication dates of the Brachyura in F.E. Guerin (Guerin-Meneville) (Crustacea: Decapoda). AB - The names and dates of the publications of Brachyura of Guerin (Guerin-Meneville from 1836) are reviewed, and previously unidentified or overlooked names are identified. Several identical new names used in multiple publications by Guerin (also under the name Guerin-Meneville), and others that appeared in the same year necessitated the accurate determination of publication dates to establish priority. The authorships of three names should be credited to Guerin (1832): Gecarcinus lateralis (Gecarcinidae), Halimus aries (Majidae), and Libinia spinosa (Epialtidae), the first previously attributed to Freminville (1835), the last two to H. Milne Edwards (1834). The overlooked genus- and species-group names Cyclocarcinus pinnotheroides Guerin-Meneville, 1838, are determined to be senior subjective synonyms of the genus- and species-group names Hapalonotus reticulatus (De Man, 1879) (Pilumnidae). Applying Article 23.9.1 of the International Code of Zoological Nomenclature, precedence is reversed between the genus-group names and the correct name is Hapalonotus pinnotheroides (Guerin-Meneville, 1838). Current and widespread use of the genus-group name Thalamita Latreille, 1829 (31 March) (Portunidae) is threatened by the overlooked Thalamites Guerin, 1829 (21 March), and the precedence of the names is also reversed to maintain usage of the former. The genus-group name Eurypodius Guerin (Inachidae) is shown to have been established in 1828, not 1825. Included is a complete bibliography of the publications in which Guerin (also under Guerin-Meneville) established new names for Brachyura, with their accurate publication dates. PMID- 25112619 TI - New records and distribution modeling of Gryne orensis (Sorensen) (Opiliones: Cosmetidae) support the Mesopotamian-Yungas disjunction in subtropical Argentina. AB - The presence of Gryne orensis (Sorensen) (Opiliones: Cosmetidae) in a Yungas locality (northwestern Argentina) is reported for the first time, providing new evidence for the Mesopotamian-Yungas disjunct pattern. Combining a total of 19 new Mesopotamian records with previous, reliable citations from the literature, a dataset of 45 points was used to model the potential distribution of the species, using the presence-only methods BIOCLIM and MAXENT. Models supported the existence of a distributional gap across the Semiarid Chaco. The imprecise literature record from "El Impenetrable", province of Chaco, is assigned to three tentative locations to evaluate if models are affected by their inclusion; in all cases, the disjunction was maintained. It was thereby estimated that the actual record might have originated in a site closer to the Humid Chaco and/or associated to streams. This paper also provides a statement of the bioclimatic profile and identification of major environmental constraints that define the range of G. orensis. PMID- 25112618 TI - Three new species of Macrelmis Motschulsky, 1859 (Coleoptera: Elmidae: Elminae) from the Brazilian Cerrado Biome with updated key for the Macrelmis of Brazil. AB - Three new species of Macrelmis Motschulsky, 1859 (Macrelmis bispo sp. nov., Macrelmis froehlichi sp. nov., and Macrelmis nessimiani sp. nov.) are herein described and illustrated. The species were collected from several streams in Goias State, Brazil, a formerly unknown region concerning Elmidae fauna. We also provide an updated key for the Macrelmis species of Brazil. PMID- 25112620 TI - Latitudinal patterns in the diversity of two subgenera of the genus Daphnia O.F. Muller (Crustacea: Cladocera: Daphniidae). AB - Daphnia O.F. Muller (Crustacea: Cladocera: Daphniidae) is an important model in biology. It was concluded earlier that subgenus Daphnia s.str. occurs mainly in the northern hemisphere, subgenus Daphnia (Ctenodaphnia) in the southern hemisphere, which could suggest that: (1) the subgeneric differentiation is correlated with the Laurasia-Gondwanaland subdivision and (2) D. (Ctenodaphnia) is a taxon of Gondwanian origin. Some authors even discussed mechanisms of maintaince of the "ancient subgeneric north-south split", regarding such a pattern as paradoxical. But both molecular clock calculations and fossils of both subgenera from the Jurassic/Cretaceous boundary of Mongolia compromise such ideas and suggest an earlier, Pangaean, differentiation of the subgenera. We discuss the distribution of Daphnia worldwide based on recent literature. Our analysis covers literature data on all described and on undescribed taxa revealed by genetical methods. Distributional data were associated with five main zones: southern cold (I), southern temperate (II), tropical (III), northern temperate (IV), and northern cold (V) zone. We found no "subgeneric north-south split": the distribution of Daphnia s.str. is dissymmetric between the hemispheres (antipolar), while that of Ctenodaphnia is sub-symmetric (bipolar). We suggest that both patterns are not of Mesozoic, but of Cenozoic origin. Mesozoic differentiation of the subgenera does not contradict a recent origin of the extant species, as found in e.g. Notostraca. A superficially attractive hypothesis about a Gondwanian origin of a taxon (Daphnia (Ctenodaphnia)) therefore did not pass the test of the fossil records. In addition, we agree with the opinion that an antipolar is only a variant of a bipolar pattern, as a result of an extinction in the southern hemisphere, and that these patterns are mid-late Cenozoic instead of Mesozoic. PMID- 25112621 TI - A new cave-dwelling millipede of the genus Scutogona from central Portugal (Diplopoda, Chordeumatida, Chamaesomatidae). AB - A new cave-dwelling species of the genus Scutogona Ribuat, 1913, S. minor n. sp., is described from caves of Sico karst in central Portugal. The classification and delimitation of Scutogona vis-a-vis related genera, in particular Meinerteuma Mauries, 1982, is discussed. PMID- 25112622 TI - Diversity of Aulacidae (Hymenoptera: Evanioidea) in the oceanic Ogasawara Islands (Japan), with description of a new species from Anijima Island. AB - In the context of the biodiversity conservation of the oceanic Ogasawara Islands, the parasitoid species of Aulacidae are reviewed. We examined material from eight islands with or without invasion of the introduced lizard Anolis carolinensis (Voigt 1832) (green anoles): two species of Pristaulacus Kieffer 1900, P. boninensis Konishi, 1989, and P. anijimensis sp. nov., are recognized. The former species is widely distributed in the islands, whereas the latter species is found from a single island only, Anijima Island. Although this island appears to be currently well preserved, the recent introduction of green anoles will probably affect the conservation status of many species, including the endemic P. anijimensis sp. nov. A description of the new species, detailed drawings and descriptions of genitalia of both recognized species, an updated key to Japanese Aulacidae, and a brief discussion on the conservation aspects of Aulacidae in the Ogasawara Islands are provided. PMID- 25112623 TI - A new species of Lakshmia Yakovlev, 2004 (Lepidoptera: Cossidae) from Northern Thailand with a world catalogue of the genus. PMID- 25112624 TI - Gerromorpha (Hemiptera: Heteroptera) of eastern Mato Grosso State, Brazil: checklist, new records, and species distribution modeling. AB - The infraorder Gerromorpha comprises semiaquatic bugs, most of which spend much of their lifetime on the water surface, between floating plants, or on the margins of water bodies. Based on literature and collections made on streams and lakes on municipalities of eastern Mato Grosso, Brazil, a list has been elaborated with 52 species, including several new records. Out of the recorded species, 26 belong to the family Veliidae, 20 to Gerridae, three to Hydrometridae, two to Mesoveliidae, and one to Hebridae. The modeling of the potential geographical distribution is also presented for the 20 species that have been recorded for the first time from the state. PMID- 25112625 TI - A new species of Physoschistura (Pisces: Nemacheilidae) from northern Thailand. AB - Physoschistura chulabhornae, new species, is described from Maechaem River, a tributary of Ping River, upper Chaophraya River drainage, Chiangmai province, Thailand. It is distinguished from all other known species of Physoschistura in having an incomplete lateral line reaching at least to the origin of the anal fin with 62-83 lateral-line canal pores, the dorsal-fin origin slightly in front of the pelvic-fin origin, no axillary pelvic lobe, and a suborbital flap in the shape of a hammer head in the male. PMID- 25112626 TI - A new species in the genus Pseudorhyncomyia Peris, 1952 and the identity of P. deserticola Zumpt and Argo, 1978 (Diptera, Rhiniidae). AB - The genus Pseudorhyncomyia Peris, 1952 is re-described and shown to have two valid species: P. braunsi (Villeneuve, 1920) and P. aethiopica sp. nov. The latter is described on the basis of a single male specimen captured near Ado, Ethiopia, in 1953. Nominal species P. deserticola Zumpt and Argo, 1978 is transferred to Zumba Peris, 1951, where it is placed as a junior synonym of Z. antennalis (Villeneuve, 1929), syn. nov. PMID- 25112627 TI - The Pselaphinae of Madagascar. II. Redescription of the genus Semiclaviger Wasmann, 1893 (Coleoptera: Staphylinidae: Pselaphinae: Clavigeritae) and synonymy of the subtribe Radamina Jeannel, 1954. AB - The enigmatic Madagascan genus Semiclaviger Wasmann is among the most morphologically distinct members of the obligately myrmecophilous pselaphine supertribe Clavigeritae. Here, the genus is redescribed, and the lectotype of the type species S. sikorae Wasmann is designated. We present a detailed study of the morphology of Semiclaviger, which supports its uniqueness among the Clavigeritae. The systematic position of the genus, and the validity of its subtribe Radamina, are discussed leading us to place Radamina in synonymy with Clavigerodina. PMID- 25112629 TI - New species of Narnia (Hemiptera: Heteroptera: Coreidae: Coreinae: Anisoscelini) from Mexico and key to the known species of the genus. AB - One new species of Narnia is described from Mexico, N. anaticula sp. nov. A key to the species is provided together with dorsal view photograph of each known species of Narnia. The genus is divided in two groups according the color of the dorsal abdominal segments. PMID- 25112628 TI - Working and reference check list for fireflies of Melanesia (Coleoptera: Lampyridae: Luciolinae). AB - Twenty-three species of Lampyridae (fifteen of them new) collected during the 1969-70 Alpha Helix scientific expedition to New Guinea are now characterized by both behavioural and taxonomic data. For ease of identification, relocation of specimens, and location of all pertinent literature this check list is presented. PMID- 25112630 TI - Redescription of Parapercis punctata (Cuvier, 1829) and status of Neosillago Castelnau, 1875 and its type species Neosillago marmorata Castelnau, 1875 (Perciformes: Pinguipedidae). AB - The status of two doubtful fish species is reviewed. Percis punctata Cuvier, 1829 is confirmed to be a valid species of Parapercis Bleeker, 1863 and a senior synonym of Parapercis guezei Fourmanoir, 1966. A redescription of Parapercis punctata is provided, based on four specimens collected from the western Indian Ocean. Examination of the holotype of Neosillago marmorata Castelnau, 1875 revealed that Neosillago is a junior synonym of Parapercis and N. marmorata is a junior synonym of Parapercis nebulosa (Quoy & Gaimard, 1825). PMID- 25112632 TI - Revision of the genus Ateralphus Restello, Iannuzzi & Marinoni, 2001 (Coleoptera: Cerambycidae: Lamiinae). AB - A revision of the genus Ateralphus Restello, Iannuzzi & Marinoni, 2001, based on the detailed study of the morphology of the type-species and on the external morphology and terminalia of the others species is presented. The genus and species are redescribed and three new species are described. The genus is composed of nine species: A. dejeani (Lane, 1973), A. javariensis (Lane, 1965), A. lacteus Galileo & Martins, 2006, A. senilis (Bates, 1862), A. subsellatus (White, 1855), A. variegatus (Mendes, 1938), A. auritarsus new species, A. lucianeae new species and A. tumidus new species. A key for identification of the species and maps of their geographical distribution are provided. PMID- 25112633 TI - The genus Yemmalysus Stusak (Hemiptera: Heteroptera: Berytidae) from China. AB - Species of the genus Yemmalysus Stusak, 1972 from China are treated in this paper: Y. parallelus Stusak, 1972 and Y. brevispinus Cai, Ye & Bu, sp. nov. Scanning electron micrographs of the head, thorax, external scent efferent system and scutellar spine, illustrations of the male genital capsules and parameres of the two species, and a key to the species of this genus are provided to assist in identification. Type specimens of Y. brevispinus sp. nov. are deposited in Institute of Entomology, College of Life Sciences, Nankai University, Tianjin, China. PMID- 25112634 TI - Description of three species of Halmyrapseudes (Crustacea: Tanaidacea: Parapseudidae), with a discussion of biogeography. AB - We describe Halmyrapseudes gutui sp. nov. from a mangrove area on Lidee Island, southern Thailand. This species closely resembles H. cooperi, H. killaiyensis, and H. thaumastocheles, but differs in having the lacinia mobilis with three teeth, and the pereopod 1 carpus with 0,1 or 1,1 ventral simple setae proximal to each spiniform seta. We redescribed and synonymized two species of questionable affiliation, Apseudes cooperi and A. digitalis, placing them in Halmyrapseudes, and partly redescribed Halmyrapseudes killaiyensis. Halmyrapseudes and Pseudohalmyrapseudes have disjunct distributions. Halmyrapseudes is similar in distribution to two freshwater fish taxa whose distributions are considered to reflect the breakup of Gondwana and subsequent continental drift. Pseudohalmyrapseudes occurs around Australia, and its distribution seems to be separated from that of Halmyrapseudes by Wallace's Line or Huxley's Line, which are distributional barriers for both terrestrial organisms and an amphidromous shrimp. The adjacent distributions and morphological similarities suggest that Halmyrapseudes and Pseudohalmyrapseudes are sister taxa. PMID- 25112635 TI - Revision of the Neotropical genus Malacophagomyia (Diptera: Sarcophagidae) with description of a new species. AB - The small Neotropical genus Malacophagomyia Lopes is revised. Two previously recorded species from tropical South America are redescribed: M. filamenta (Dodge) and M. kesselringi Kano & Lopes. One new species is described, M. rivadavia sp. nov., from temperate southern South America. The structures of the male genitalia of the species of this genus are compared, and some female genitalic structures of M. filamenta are reinterpreted. Diagnostic characters to recognize the three species are given. Additionally, a key to described species of Malacophagomyia is presented. PMID- 25112636 TI - Two new genera and species of Tingidae from Cretaceous amber from Myanmar (Burma) (Hemiptera: Heteroptera). AB - From the Upper Cretaceous Burmese amber, the first known genera of Tingidae, Spinitingis n. gen. and Burmacader n. gen. with the species Spinitingis ellenbergeri n. sp. and Burmacader multivenosus n. sp., are described and figured. Their systematic placement and relationship to fossil and extant taxa are discussed. PMID- 25112637 TI - A new genus of Saucrosmylinae (Insecta, Neuroptera) from the Middle Jurassic of Daohugou, Inner Mongolia, China. AB - A new genus and new species of Saucrosmylinae (Insecta, Neuroptera) is described as Huiyingosmylus bellus gen. et sp. nov., based on a well-preserved forewing from the Middle Jurassic of Daohugou, Inner Mongolia, China. Huiyingosmylus gen. nov. is characterized by the large size of forewing, relatively wide R1 space with several rows of cells, anteriorly bent Rs, dense crossveins over the entire wing and undulate outer margin. A key to the genera of Saucrosymylinae is provided. PMID- 25112638 TI - Two new species of Lachesilla in the andra group, from the Chapada Diamantina, Bahia, Brazil (Psocodea: 'Psocoptera': Lachesillidae). AB - Two new species of Lachesilla in the andra group are described from Brazil, where the group was previously unknown. They raise to five the number of species in the group known in South America. An identification key for females of the andra group in South America is included. PMID- 25112639 TI - Two new species of Hemielimaea Brunner von Wattenwyl from China. AB - Two new species Hemielimaea (Hemielimaea) paracari sp. nov. and H. (H.) parva sp. nov. from southwestern China are described. Characteristics of the stridulatory file on underside of male left tegmen, male stridulatory area on left and right tegmen, and abdominal apex of male are provided. Important and necessary illustrations of the new species are presented. Materials come from the following two depositories: Institute of Zoology, Chinese Academy of Sciences, Beijing, China (IZCAS), and China Agricultural University, Beijing, China (CAU). PMID- 25112640 TI - Revision of the Empis subgenus Enoplempis Bigot, east of the Rocky Mountains (Diptera: Empididae). AB - The Empis subgenus Enoplempis Bigot, east of the Rocky Mountains of North America is revised. A total of 19 species are recorded from this region including seven new species: E. (En.) amytis Walker, E. (En.) appalachicola Sinclair sp. nov., E. (En.) arthritica Melander, E. (En.) ctenonema Melander, E. (En.) enodis Melander, E. (En.) gladiator Melander, E. (En.) gulosa Coquillett, E. (En.) loripedis Coquillett, E. (En.) montywoodi Brooks sp. nov., E. (En.) nodipoplitea Steyskal, E. (En.) nuda Loew, E. (En.) pectinata Sinclair sp. nov., E. (En.) penicillata Brooks sp. nov., E. (En.) prodigiosa Cumming sp. nov., E. (En.) snoddyi Steyskal, E. (En.) stenoptera Loew, E. (En.) tridentata Coquillett, E. (En.) vockerothi Cumming sp. nov., E. (En.) volsella Sinclair sp. nov. The following new synonymies are designated: E. (En.) longipes Loew, E. (En.) longeoblita Steyskal, E. (En.) deterra Walley = E. (En.) amytis; E. (En.) cacuminifer Melander = E. (En.) gulosa. Lectotypes are designated for the following species: E. (En.) arthritica, E. (En.) cacuminifer, E. (En.) ctenonema, E. (En.) enodis, E. (En.) gladiator, E. (En.) loripedis, E. (En.) stenoptera and E. (En.) tridentata. A key to eastern species is presented and distributions illustrated. The form of nuptial gift presentation displayed within this group, including the use of balloons (with or without prey) and unwrapped prey are indicated for species when known. PMID- 25112641 TI - Redefinition of the genus Silphitrombium (Trombidiformes: Neothrombiidae) with description of two new species parasitizing beetles (Coleoptera: Elateridae, Tenebrionidae) from Iran. AB - Two new species of Silphitrombium Fain, 1992 (Acari: Prostigmata: Neothrombiidae), ectoparasites of beetles (Insecta: Coleoptera), are described from Sistan and Baluchestan Province, eastern Iran: S. elateridum sp. nov. on Heteroderes heideni Reitter, 1891 (Col.: Elateridae) and S. iranicum sp. nov. on Opatroides punctulatus Brulle, 1832 (Col.: Tenebrionidae) and the genus Silphitrombium is redefined. It is the first record of the relationship between beetles of the families Elateridae and Tenebrionidae, and mites of the genus Silphitrombium. A key to the species of the genus is presented. PMID- 25112642 TI - Four new species of Acoela from Chile. AB - Acoels are with few exceptions marine worms and a common component of the interstitial meiofauna. In this study we present new species to science belonging to Isodiametridae and Solenofilomorphidae. The new species, Isodiametra finkei n. sp., Postaphanostoma nilssoni n. sp., Pseudaphanostoma hyalinorhabdoida n. sp. and Solenofilomorpha pellucida n. sp. were all collected in Chile during March 2012. Nucleotide sequences for the ribosomal genes 18S rDNA and 28S rDNA as well as COI mtDNA have been determined for the new species and used in a maximum likelihood analysis to further support their classification. PMID- 25112643 TI - Morphology of a neglected large-sized species of Geophilus from Iran (Chilopoda: Geophilidae). AB - Geophilus gigas was described briefly by Attems in 1951 from two sites in Iran, but neither reported nor cited subsequently. The original description is inadequate to understand the full morphology and the taxonomic position of the species. Thus it is here redescribed and figured in detail based on the examination of a syntype and newly collected specimens. Furthermore it is compared with the most similar species of the genus Geophilus. G. gigas can be reliably distinguished from other related species for the maximum body size (more than 6 cm), the arrangement and extent of the sternal pore-fields (with additional groups of pores), the coxal pores number and distribution (tens, scattered), and the size of the ultimate legs (swollen in both sexes). PMID- 25112644 TI - Review of the largest species group of the New World seed beetle genus Sennius Bridwell (Coleoptera: Chrysomelidae), with host plant associations. AB - Sennius Bridwell is a New World genus of Bruchinae. Most species are placed in eight groups. In this study the species of the S. abbreviatus group are reviewed based on characters of the external morphology and the male genitalia. The group includes 14 species, two of which are new: Sennius abbreviatus (Say, 1824), S. bondari (Pic, 1929), S. durangensis Johnson & Kingsolver, 1973, S. lawrencei Johnson, 1977, S. lebasi (Fahraeus, 1839), S. leucostauros Johnson & Kingsolver, 1973, S. lojaensis (Pic, 1933), S. medialis (Sharp, 1885), S. nappi Ribeiro-Costa & Reynaud, 1998, S. rufomaculatus (Motschulsky, 1874), S. transversesignatus (Fahraeus, 1839), S. trinotaticollis (Pic, 1930), S. vivi sp. nov. and S. flinte sp. nov. The S. abbreviatus group differs from other groups by the pattern of sclerites and the shape of the internal sac of the male genitalia, and has three subgroups, defined here. The lectotype of S. lebasi is designated. New host plant records are presented for S. lojaensis and S. transversesignatus, and new distribution records for S. lawrencei, S. lojaensis and S. trinotaticollis. PMID- 25112645 TI - Review of the genus Cystocnemis (Coleoptera: Chrysomelidae: Chrysomelinae) with descriptions of two new species . AB - Two new species of Cystocnemis (s. str.) Motschulsky, 1860 namely C. levmedvedevi sp. nov. and C. zintshenkoi sp. nov. are described from the Mongolian Altai (Mongolia, Hovd aimag) and Southern Altai (Kazakhstan, East-Kazakhstan region) respectively. Generic diagnosis as well as key to species and subspecies of Cystocnemis are provided. Zoogeographical affinities of Entomoscelini are discussed. PMID- 25112646 TI - Five new eyed species of Sinella (Collembola: Entomobryidae) from China, with a key to the eyed species of the genus. AB - Five new eyed species of Sinella from China, respectively with 3, 3, 2, 1, 1 ommatidia on each side, are described here: S. longisensilla sp. nov., S. yui sp. nov., S. pseudobrowni sp. nov., S. sacellum sp. nov. and S. gracilis sp. nov. Clypeal chaetae and chaetae along cephalic groove exhibit differences among these species and could be used to distinguish species in Sinella and Coecobrya. A key to the eyed species of the genus is given. PMID- 25112647 TI - Non-biting midges of the tribe Tanytarsini in Eocene amber from the Rovno region (Ukraine): a pioneer systematic study with notes on the phylogeny (Diptera: Chironomidae). AB - The first detailed systematic study on the tanytarsine chironomids recorded in the Eocene amber from the Rovno region (Ukraine) revealed seven new taxa. Archistempellina gen. nov., represented by A. bifurca sp. nov. (type for the genus, male) and A. falcifera sp. nov. (male), displays characters similar to those found in Stempellina Thienemann et Bause, and is recognized as one of probable basal lineages in the subtribe Stempellinina Shilova. Corneliola gen. nov., represented by C. avia sp. nov. (male, female), combines features known from several genera of the tribe Tanytarsini, and tentatively is regarded as the closest relative of Constempellina Brundin. Rheotanytarsus alliciens sp. nov. (male), featuring a long hypopygial digitus, is considered to be the oldest species of the genus. Tanytarsus congregabilis sp. nov. (male) is the first known Eocene representative of the lugens systematic species group. A complemented description of the male of Tanytarsus serafini Gilka is provided as well. PMID- 25112648 TI - The mammal type specimens at the Natural History Museum, University of Oslo, Norway. AB - A catalog of mammalian type specimens in the collections of Natural History Museum, University of Oslo, Norway, is presented. All type specimens in the Museum's mammal collection were revisited and the respective label information was compared with the data provided in the original descriptions. Most taxa were described from type series with no specimen particularly assigned to holotype. The compiled catalog of the type specimens is not intended as a taxonomic revision of the respective taxa, which is why we have not designated lectotypes from the collection's type series. Specimens that were clearly marked as "the type" in the original description were considered holotypes. The catalog consists of 19 taxa, with the year of authority corrected for three taxa. PMID- 25112649 TI - A new Odontothrips species (Thysanoptera: Thripidae) from Iran . PMID- 25112650 TI - Testing departure from additivity in Tukey's model using shrinkage: application to a longitudinal setting. AB - While there has been extensive research developing gene-environment interaction (GEI) methods in case-control studies, little attention has been given to sparse and efficient modeling of GEI in longitudinal studies. In a two-way table for GEI with rows and columns as categorical variables, a conventional saturated interaction model involves estimation of a specific parameter for each cell, with constraints ensuring identifiability. The estimates are unbiased but are potentially inefficient because the number of parameters to be estimated can grow quickly with increasing categories of row/column factors. On the other hand, Tukey's one-degree-of-freedom model for non-additivity treats the interaction term as a scaled product of row and column main effects. Because of the parsimonious form of interaction, the interaction estimate leads to enhanced efficiency, and the corresponding test could lead to increased power. Unfortunately, Tukey's model gives biased estimates and low power if the model is misspecified. When screening multiple GEIs where each genetic and environmental marker may exhibit a distinct interaction pattern, a robust estimator for interaction is important for GEI detection. We propose a shrinkage estimator for interaction effects that combines estimates from both Tukey's and saturated interaction models and use the corresponding Wald test for testing interaction in a longitudinal setting. The proposed estimator is robust to misspecification of interaction structure. We illustrate the proposed methods using two longitudinal studies-the Normative Aging Study and the Multi-ethnic Study of Atherosclerosis. PMID- 25112651 TI - Total versus unicompartmental knee replacement for isolated lateral osteoarthritis: a matched-pairs study. AB - PURPOSE: The aim of this study was to compare the functional outcome of patients following unicompartmental knee replacement (UKR) using the Oxford domed lateral UKR to patients who underwent cruciate-retaining total knee replacement (TKR) for isolated osteoarthritis in the lateral compartment. METHODS: With the help of our institutional database, we retrospectively identified 22 matched pairs with regards to age, gender and body mass index (BMI). Functional outcome was measured using the Oxford Knee Score (OKS) and range of motion (ROM). Complications and revisions were recorded. RESULTS: The mean follow-up was 22 (UKR) and 19 (TKR) months, respectively. Patients following UKR had a statistically significant higher mean postoperative OKS and ROM: mean OKS was 43 [standard deviation (SD) 4] for UKR and 37 (SD 9) for TKR, respectively (p = 0.023); ROM was 127 degrees (SD 13) for UKR and 107 degrees (SD 17) for TKR (p < 0.001). Additionally the change in score was statistically significant higher in patients following UKR in the OKS (14.3 (SD 6) vs. 9.6 (SD 8)) and in the range of motion (+12 degrees (SD 19) vs. -3 degrees (SD 20)), (p = 0.041 and p = 0.01 respectively). Survival at two years using revision for any reason as the endpoint was 96% [95% confidence interval (CI) 72-99] for UKR and 100% for TKR (Log-rank test, p = 0.317). CONCLUSION: The functional results of mobile-bearing UKR for isolated osteoarthritis in the lateral compartment compare favourably to those after cruciate-retaining TKR in the short term. To compare survival and complications after both procedures, longer-term follow-up is necessary. PMID- 25112652 TI - Synthesis of nitrogen-doped zigzag-edge peripheries: dibenzo-9a-azaphenalene as repeating unit. AB - A bottom-up approach toward stable and monodisperse segments of graphenes with a nitrogen-doped zigzag edge is introduced. Exemplified by the so far unprecedented dibenzo-9a-azaphenalene (DBAPhen) as the core unit, a versatile synthetic concept is introduced that leads to nitrogen-doped zigzag nanographenes and graphene nanoribbons. PMID- 25112654 TI - Attitude of physiotherapy students in Nigeria toward persons with disability. AB - BACKGROUND: Attitudes of students of health care professions, such as physiotherapy, toward persons with disability may influence their attitude and practice post-qualification. OBJECTIVE: To examine attitudes toward persons with disability among undergraduate physiotherapy students in Universities in Nigeria. METHODS: The 30-item Attitudes toward Disabled Persons--Form A (ATDP-A) scale was used to assess the attitudes of penultimate and final year physiotherapy students in 3 Nigerian universities. Overall and item-by-item analyzes of responses to the ATDP-A scale were carried out. Differences in attitude by sex, age, year and university of study were also examined using independent t-test and one-way ANOVA. RESULTS: One hundred and sixty-nine students with a male majority (56.2%) participated in the study. Mean score on the ATDP-A was 94.95 +/- 17.50 with more students (60.4%) having a score >90 which depicts positive attitude. Item-by-item analysis of responses to the 30 items on the ATDP-A showed that negative attitudes were preponderant on items relating to the emotional component of the personality of persons with disability. Only age of students and their university of study however resulted in statistically significant differences in attitudes and older students reported better attitudes toward persons with disability. CONCLUSIONS: Although the overall attitude of the physiotherapy students was positive, negative stereotypes and discriminatory tendencies were observed in issues relating to the perceived emotional capacity of persons with disabilities. Educational strategies capable of effecting more positive attitudes in physiotherapy students in Nigeria toward persons with disability are urgently needed. PMID- 25112655 TI - Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation. PMID- 25112653 TI - Emergency department provider preferences related to clinical practice guidelines for tobacco cessation: a multicenter survey. AB - OBJECTIVES: The objective was to assess current emergency department (ED) provider practices and preferences for tobacco cessation interventions. The ED is an opportune place to initiate smoking cessation interventions. However, little is known about ED provider current practices and preferences for cessation counseling in the ED. METHODS: This was a survey of ED providers conducted in 2008-2009 (including physicians, nurse practitioners, physician assistants, and nurses), working at least half-time at 10 U.S. academic EDs, regarding adherence to clinical practice guidelines ("5 As") and preferences for cessation interventions/styles. Data analysis occurred in 2012-2013. RESULTS: The response rate was 64% (800 out of 1,246 completed surveys). Providers reported strongest adherence to asking about patient smoking status, followed by advising, with significant variance by clinical role. Assessing, assisting, and arranging support for patients was low overall. Most frequently used interventions were to provide patients with a list of telephone numbers for stop-smoking counseling (87%), pamphlets on smoking health risks and the benefits of stopping (85%), and referrals to the National Toll-Free Smoker's Quitline (84%). Most providers (80%) were supportive of personally conducting brief (less than 3 minutes) smoking cessation counseling sessions during the ED visit, emphasizing education and encouragement. The least appealing intervention was writing a prescription for nicotine replacement therapies or medications to stop smoking (35%). CONCLUSIONS: Interventions most likely to be used were brief and delivered with a positive tone and included referral to external resources. The logical next step is to design and test interventions that ED providers find acceptable. PMID- 25112656 TI - Geriatric emergency department innovations: preliminary data for the geriatric nurse liaison model. AB - Older adults account for a large and growing segment of the emergency department (ED) population. They are often admitted to the hospital for nonurgent conditions such as dementia, impaired functional status, and gait instability. The aims of this geriatric ED innovations (GEDI) project were to develop GEDI nurse liaisons by training ED nurses in geriatric assessment and care coordination skills, describe characteristics of patients that these GEDI nurse liaisons see, and measure the admission rate of these patients. Four ED nurses participated in the GEDI training program, which consisted of 82 hours of clinical rotations in geriatrics and palliative medicine, 82 hours of didactics, and a pilot phase for refinement of the GEDI consultation process. Individuals were eligible for GEDI consultation if they had an Identification of Seniors At Risk (ISAR) score greater than 2 or at ED clinician request. GEDI consultation was available Monday through Friday from 9:00 a.m. to 8:00 p.m. An extensive database was set up to collect clinical outcomes data for all older adults in the ED before and after GEDI implementation. The liaisons underwent training from January through March 2013. From April through August 2013, 408 GEDI consultations were performed in 7,213 total older adults in the ED (5.7%, 95% confidence interval (CI) = 5.2 6.2%), 2,124 of whom were eligible for GEDI consultation (19.2%, 95% CI = 17.6 20.9%); 34.6% (95% CI = 30.1-39.3%) received social work consultation, 43.9% (95% CI = 39.1-48.7) received pharmacy consultation, and more than 90% received telephone follow-up. The admission rate for GEDI patients was 44.9% (95% CI = 40.1-49.7), compared with 60.0% (95% CI = 58.8-61.2) non-GEDI. ED nurses undergoing a 3-month training program can develop geriatric-specific assessment skills. Implementation of these skills in the ED may be associated with fewer admissions of older adults. PMID- 25112657 TI - New advances in the treatment of atrial fibrillation: focus on stroke prevention. AB - INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and brings about significant mortality and morbidity as a result of heart failure and ischemic stroke. Besides vitamin K antagonists (VKA), several new pharmacological agents (nonvitamin K antagonist oral anticoagulants [NOACs]) and procedures have since been developed to improve stroke prevention efforts in AF. AREAS COVERED: This paper will discuss the antiplatelet agents, VKA and NOACs, and their efficacy and safety for stroke prevention in AF. Focus will be placed on the NOACs, their limitations and special considerations. A short assessment of other nonpharmacological antithrombotic procedures will also be made. An extensive PubMed search was used to identify suitable papers. EXPERT OPINION: Despite the advent of NOACs, the VKAs will remain as an important oral anticoagulant due to its versatility. However, convenience and limited food or drug interactions will make NOACs attractive options. The choice between various NOACs will depend on several important factors as illustrated below. Over time, the role for antiplatelet agents will gradually diminish. Left atrial appendage occlusion devices have shown promising results and may have the potential to change the way clinicians manage thromboembolism risks related to AF. PMID- 25112658 TI - Reirradiation as part of a salvage treatment approach for progressive non-pontine pediatric high-grade gliomas: preliminary experiences from the German HIT-HGG study group. AB - BACKGROUND AND PURPOSE: The aim of the present analysis was to assess the feasibility, toxicity, and the tumor control of reirradiation as a salvage treatment for progressive pediatric non-pontine high-grade gliomas (HGG). PATIENTS AND METHODS: The database of the Reference Center for Radiation Oncology of the German HIT (HIT = German acronym for brain tumor) treatment network for childhood brain tumors was screened for children who were reirradiated for progressive non-pontine HGG. RESULTS: We identified eight patients (WHO grade III: n = 5; WHO grade IV: n = 3) who underwent reirradiation between April 2006 and July 2012. Median age was 13.5 years at primary diagnosis and 14.8 years at first progression. All patients initially underwent surgery (incomplete resection, n = 7; biopsy, n = 1) followed by radiochemotherapy. Relapses occurred inside (n = 2), at the margin (n = 4), and outside of the preirradiated area (n = 2). In all patients, reirradiation was tolerated well without significant acute toxicity. Temporary clinical improvement and tumor regression on magnetic resonance imaging (MRI) following reirradiation was reported (n = 3). However, all patients finally died by disease progression. Median survival time was 26.2 months from initial diagnosis and 11.4 months after first progression. Median time interval between initial radiotherapy and first reirradiation was 9.0 months. In six patients, all macroscopic tumor deposits were reirradiated. In these patients, median progression-free (overall) survival from the start of reirradiation was 2.4 (4.6) months. CONCLUSION: Our analysis, although based on a limited patient number, suggests that reirradiation of progressive non-pontine HGG is feasible in children. Benefit in terms of quality of life and/or survival needs to be assessed in a prospective and ideally in a randomized manner. PMID- 25112659 TI - BDNF contributes to the facilitation of hippocampal synaptic plasticity and learning enabled by environmental enrichment. AB - Sensory, motor, and cognitive stimuli, resulting from interactions with the environment, play a key role in optimizing and modifying the neuronal circuitry required for normal brain function. An experimental animal model for this phenomenon comprises environmental enrichment (EE) in rodents. EE causes profound changes in neuronal and signaling levels of excitation and plasticity throughout the entire central nervous system and the hippocampus is particularly affected. The mechanisms underlying these changes are not yet fully understood. As brain derived neurotrophic factor (BDNF) supports hippocampal long-term potentiation (LTP), we explored whether it participates in the facilitation of synaptic plasticity and hippocampus-dependent learning that occurs following EE. In the absence of EE, LTP elicited by high-frequency stimulation was equivalent in wildtype mice and heterozygous BDNF(+/-) siblings. LTP elicited by theta-burst stimulation in BDNF(+/-) mice was less than in wildtypes. Long-term depression (LTD) was also impaired. EE for three weeks, beginning after weaning, improved hippocampal LTP in both wildtype and transgenic animals, with LTP in transgenics achieving levels seen in wildtypes in the absence of EE. Object recognition memory was evident in wildtypes 24 h and 7 days after initial object exposure. EE improved memory performance in wildtypes 24 h but not 7 days after initial exposure. BDNF(+/-) mice in the absence of EE showed impaired memory 7 days after initial object exposure that was restored by EE. Western blotting revealed increased levels of BDNF, but not proBDNF, among both EE cohorts. These data support that BDNF plays an intrinsic role in improvements of synaptic plasticity and cognition that occur in EE. PMID- 25112660 TI - Subacute presentation of eyebrow intravascular papillary endothelial hyperplasia causing ophthalmic nerve compression. PMID- 25112661 TI - Percutaneous closure of patent foramen ovale in patients with cryptogenic embolism: a network meta-analysis. AB - BACKGROUND: Up to 40% of ischaemic strokes are cryptogenic. A strong association between cryptogenic stroke and the prevalence of patent foramen ovale (PFO) suggests paradoxical embolism via PFO as a potential cause. Randomized trials failed to demonstrate superiority of PFO closure over medical therapy. METHODS AND RESULTS: Randomized trials comparing percutaneous PFO closure against medical therapy or devices head-to-head published or presented by March 2013 were identified through a systematic search. We performed a network meta-analysis to determine the effectiveness and safety of PFO closure with different devices when compared with medical therapy. We included four randomized trials (2963 patients with 9309 patient-years). Investigated devices were Amplatzer (AMP), STARFlex (STF), and HELEX (HLX). Patients allocated to PFO closure with AMP were less likely to experience a stroke than patients allocated to medical therapy [rate ratio (RR) 0.39; 95% CI: 0.17-0.84]. No significant differences were found for STF (RR 1.01; 95% CI: 0.44-2.41), and HLX (RR, 0.71; 95% CI: 0.17-2.78) when compared with medical therapy. The probability to be best in preventing strokes was 77.1% for AMP, 20.9% for HLX, 1.7% for STF, and 0.4% for medical therapy. No significant differences were found for transient ischaemic attack and death. The risk of new-onset atrial fibrillation was more pronounced for STF (RR 7.67; 95% CI: 3.25-19.63), than AMP (RR 2.14; 95% CI: 1.00-4.62) and HLX (RR 1.33; 95%-CI 0.33-4.50), when compared with medical therapy. CONCLUSIONS: The effectiveness of PFO closure depends on the device used. PFO closure with AMP appears superior to medical therapy in preventing strokes in patients with cryptogenic embolism. PMID- 25112665 TI - Combined detection of coronary artery disease and lung cancer. PMID- 25112662 TI - The association between biventricular pacing and cardiac resynchronization therapy-defibrillator efficacy when compared with implantable cardioverter defibrillator on outcomes and reverse remodelling. AB - AIMS: Previous studies on biventricular (BIV) pacing and cardiac resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily chosen BIV pacing percentages, and no study has employed implantable cardioverter defibrillator (ICD) patients as a control group. METHODS AND RESULTS: Using Kaplan-Meier plots, we estimated the threshold of BIV pacing percentage needed for CRT-D to be superior to ICD on the end-point of heart failure (HF) or death in 1219 left bundle branch block (LBBB) patients in the MADIT-CRT trial. Patients were censored at the time of crossover. In multivariable Cox analyses, no difference was seen in the risk of HF/death between ICD and CRT-D patients with BIV pacing <=90% [HR = 0.78 (0.47-1.30), P = 0.344], and with increasing BIV pacing the risk of HF/death was decreased [CRT-D BIV 91-96% vs. ICD: HR = 0.63 (0.42-0.94), P = 0.024 and CRT-D BIV >=97% vs. ICD: HR = 0.32 (0.23-0.44), P < 0.001]. The risk of death alone was reduced by 52% in CRT-D patients with BIV >=97% (HR = 0.48, P < 0.016), when compared with ICD patients. Within the CRT-D group, for every 1 percentage point increase in BIV pacing, the risk of HF/death and death alone significantly decreased by 6 and 10%, respectively. Increasing BIV pacing percentage was associated with significant reductions in left ventricular volume. CONCLUSION: In patients with LBBB, who were in sinus rhythm at enrolment, BIV pacing exceeding 90% was associated with a benefit of CRT-D in HF/death when compared with ICD patients. Furthermore, BIV pacing >=97% was associated with an even further reduction in HF/death, a significant 52% reduction in death alone, and increased reverse remodelling. Clinical trials.gov identifier: NCT00180271. PMID- 25112666 TI - Verwijzen naar het hospice: verwijsgedrag van artsen en ervaren belemmeringen in Deventer en omgeving. AB - PHYSICIANS' REFERRAL PATTERNS AND PERCEIVED BARRIERS IN THE DEVENTER REGION IN THE NETHERLANDS: OBJECTIVE: To examine physicians' perceived referral patterns and barriers to referral of terminally ill patients to a hospice (institute). DESIGN: Survey study among physicians practicing in hospital and other settings in the region of Deventer, The Netherlands, in 2011-2012. METHOD: We translated two available American instruments into Dutch. The questionnaire assessed hospice referral, knowledge about hospice, attitudes and barriers and reasons not to refer. We queried physicians who had referred patients to the local hospice about expectations and suggested areas for improvement with two open-ended items. RESULTS: In total, 240 physicians received the questionnaire. The response rate was 47%. The physicians were generally positive about hospice care. They indicated experiencing few barriers in hospice referrals, but 32% of the physicians (21% of those practicing in the hospital, and 39% in other settings), indicated the patient being unready as a strong barrier. Half of the physicians (51%) believed that hospice is being underutilized and 22% (35% and 14%, respectively) thought that they would refer more frequently if they had more knowledge about hospice care. Of the physicians, 35% answered all six knowledge questions correctly. Communication with the hospice may be improved. CONCLUSION: Despite positive attitudes toward hospice care, it may be underutilized due to poor knowledge and communication with the hospice. Perhaps, this is also due to limited patient-physician communication on prognosis, which further research may address. PMID- 25112667 TI - [TRANSITION OF A PSYCHOGERIATRIC DAY CARE IN THE NURSING HOME TO EASY-ACCESS DAY CARE PLUS CAREGIVER SUPPORT IN THE COMMUNITY: A PILOT STUDY]. AB - BACKGROUND: In this study, the transition of a nursing home based psychogeriatric day care centre to an easy-access community day care centre plus caregiver support (DC-plus CS) is followed closely. The transition was based on the proven effective Meeting Centres Support Program. METHOD: By means of qualitative analysis of documents and interviews with key persons (n=11) we investigate facilitating and impeding factors for making this transition. Besides, we evaluate the satisfaction of participants and informal caregivers that used the new support program longer than 6 months. RESULTS: Several characteristics of the innovation (DC-plus CS) help to establish cooperation with other care and welfare services in the region, such as: the easy-access location, the social integration in the community, and the focus on combined support for people with dementia and their informal carers. The good cooperation and the suitable location in the community facilitate the implementation. At first, the presence of other community care-centres for people with dementia and their informal carers in the neighbourhood impedes the recruitment of new participants for the DC-plus CS. In general, the satisfaction of participants and informal carers about the support program is high. CONCLUSION AND DISCUSSION: The transition is made successfully and this study gives other psychogeriatric day care centres in the nursing home insight in how to make a similar transition to DC-plus CS. PMID- 25112668 TI - 'Soya milk Tris-based phytoextender reduces apoptosis in cryopreserved buffalo (Bubalus bubalis) spermatozoa'. AB - The objective of this study was to investigate the effect of newly developed soya milk Tris (SMT)-based phytoextender as an alternative to egg yolk Tris (EYT) extender used for cryopreservation of buffalo (Bubalus bubalis) spermatozoa on apoptosis. Fresh buffalo semen (control without dilution) was cryopreserved in conventional EYT (20% egg yolk v/v in Tris) and SMT (25% soya milk v/v in Tris) extender and used for the assessment of expression of apoptotic proteins. Proteins extracted from a total number of nine ejaculates from three individual buffalo bulls chosen at random were separated using SDS-PAGE followed by immunoblotting against caspase-8, caspase-9, caspase-3, poly(ADP ribose)polymerase (PARP), cytochrome c and apoptosis inducing factor (AIF). In addition, fluorescence microscopy was used for the detection of mitochondrial membrane potential (JC-1 assay) and apoptotic cells (annexin V-FITC/PI assay). The results obtained clearly indicate the significant (p < 0.05) reduction in the expression of caspase-3 (27 kDa), caspase-8 (53 kDa), caspase-9 (50 kDa) precursor and cytochrome c (17 kDa) in semen cryopreserved in SMT extender in comparison with EYT extender. A non-significant (p > 0.05) reduction in expression of PARP-DNA-binding subunit (24 kDa) was observed in SMT extender. No expression of AIF was found in cryopreserved semen samples. A significant (p < 0.05) increase in the mean percentage of cells having high mitochondrial membrane potential and a non-significant (p > 0.05) decrease in late apoptotic cells (AN+/PI+) was observed in SMT extender when compared to EYT extender. The results demonstrated that cryopreservation of buffalo semen in SMT-based phytoextender can replace the traditional egg yolk extenders as it reduces the expression of apoptotic proteins maintaining high mitochondrial membrane potential and gives better protection to sperms in terms of its non-animal origin. PMID- 25112669 TI - Comparison of pregnancy and lactation labeling for attention-deficit hyperactivity disorder drugs marketed in Australia, the USA, Denmark, and the UK. AB - BACKGROUND: Pregnancy and lactation labeling is presented in the officially recognized product information (PI) accompanying prescription drugs to ensure appropriate prescribing in pregnant and breastfeeding women. OBJECTIVE: The aim of this study was to analyze pregnancy and lactation labeling in PI for attention deficit hyperactivity disorder drugs marketed across countries and to compare this information with respect to consistency and discrepancy. METHODS: We manually surveyed PI for atomoxetine, methylphenidate, and modafinil marketed by the same pharmaceutical companies in Australia, the USA, Denmark, and the UK. We extracted information regarding data sources (animal and human data), risk to the fetus or breastfed child, excretion in breast milk, and recommendations for use. The extracted information was then analyzed and compared with respect to consistency and discrepancy. RESULTS: Inter-country discrepancies were identified with respect to both animal and human data sources presented, types of risks listed in association with exposure during pregnancy and lactation, information regarding excretion of the drug in breast milk, and recommendations for use. Consistency was identified between PI for drugs marketed in the EU. CONCLUSION: The study suggests that pregnancy and lactation labeling in PI for drugs marketed by the same pharmaceutical companies depend on the country of marketing; this raises concern about the reliability of PI documents as a useful source of information for appropriate prescribing during pregnancy and lactation. Discrepancies in this information can potentially lead to inappropriate prescribing in pregnant and breastfeeding women, who may expose their fetuses and breastfed children to unnecessary risks. At the same time, unjustified warnings against breastfeeding may result in children being unnecessarily weaned from being breastfed. PMID- 25112670 TI - Response to "diffusion-weighted MR imaging findings in a growing problem: hepatic alveolar echinococcosis". PMID- 25112663 TI - Establishing reference values for central blood pressure and its amplification in a general healthy population and according to cardiovascular risk factors. AB - AIMS: Estimated central systolic blood pressure (cSBP) and amplification (Brachial SBP-cSBP) are non-invasive measures potentially prognostic of cardiovascular (CV) disease. No worldwide, multiple-device reference values are available. We aimed to establish reference values for a worldwide general population standardizing between the different available methods of measurement. How these values were significantly altered by cardiovascular risk factors (CVRFs) was then investigated. METHODS AND RESULTS: Existing data from population surveys and clinical trials were combined, whether published or not. Reference values of cSBP and amplification were calculated as percentiles for 'Normal' (no CVRFs) and 'Reference' (any CVRFs) populations. We included 45,436 subjects out of 82,930 that were gathered from 77 studies of 53 centres. Included subjects were apparently healthy, not treated for hypertension or dyslipidaemia, and free from overt CV disease and diabetes. Values of cSBP and amplification were stratified by brachial blood pressure categories and age decade in turn, both being stratified by sex. Amplification decreased with age and more so in males than in females. Sex was the most powerful factor associated with amplification with 6.6 mmHg (5.8-7.4) higher amplification in males than in females. Amplification was marginally but significantly influenced by CVRFs, with smoking and dyslipidaemia decreasing amplification, but increased with increasing levels of blood glucose. CONCLUSION: Typical values of cSBP and amplification in a healthy population and a population free of traditional CVRFs are now available according to age, sex, and brachial BP, providing values included from different devices with a wide geographical representation. Amplification is significantly influenced by CVRFs, but differently in men and women. PMID- 25112671 TI - Reply to: comment on: CT analysis of the effect of pirfenidone in patients with idiopathic pulmonary fibrosis. PMID- 25112672 TI - Diffusion-weighted MR imaging findings in a growing problem: hepatic alveolar echinococcosis. AB - Hepatic alveolar echinococcosis (AE) is a rare parasitic disease which simulates slow growing malignant processes. Cross-sectional imaging techniques play important role in differentiating between AE lesions and malignant processes such as cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC). Diffusion-weighted (DW) MRI is a non-invasive technique, which can be used for liver lesion detection and characterisation as benign or malignant in recent years. Both conventional MRI and non-contrast enhanced CT images may be insufficient the differential diagnosis in hepatic AE lesions particularly in solid components. In our study, we have performed to differentiate hepatic AE lesions from HCC and CCC lesions of the liver by using DW MRI and tried to define ADC value of hepatic AE lesions for differentiation from malignant hepatic lesions. PMID- 25112673 TI - Incidence and classification of neointimal proliferation and in-stent restenosis in post-stenting patients at 1-year interval: findings from non-invasive coronary computed tomography angiography. AB - OBJECTIVES: To evaluate the incidence of coronary in-stent restenosis (ISR) and neointimal proliferation by coronary CT angiography (CCTA) at 1-year follow-up in asymptomatic patients. METHODS: 234 patients (mean age: 67 +/- 10.2 years, range 39-88 years, 180 males and 54 females) with 379 stents were prospectively enrolled in this study. Binary ISR was classified by CCTA into 4 types using Mehran classification. Neointimal proliferation was similarly classified into focal and diffuse types. All patients with CCTA-revealed ISR or neointimal proliferation underwent further invasive coronary angiography (ICA) for validation. Fisher's exact test was used for comparison. RESULTS: ICA revealed patent stents with neointimal proliferation in 39 patients (16.7%, 39/234) and binary ISR in 23 patients (9.8%, 23/234). Lesion-based analysis showed 12 type I ISR lesions, 4 type II ISR lesions, 1 type III ISR lesion and 7 type IV ISR lesions. Among cases with neointimal proliferation, 27 lesions were classified as focal type whereas 13 lesions were classified as diffuse type. Patients with diabetes mellitus were associated with higher incidence of CCTA-revealed neointimal proliferation (21/77 vs. 18/157, p=0.002) as well as ISR (12/77 vs. 11/157, p=0.038), compared to patients without diabetes. CCTA was found to have good diagnostic performance for neointimal proliferation and ISR detection as well as classification, with an overall accuracy of 84.4% (54/64). CONCLUSIONS: Silent ISR as well as neointimal proliferation is not uncommon findings in asymptomatic post-stenting patients at 1-year interval, as revealed by CCTA. Patients with diabetes are prone to have higher incidence of neointimal proliferation. PMID- 25112674 TI - Laboratory tests during direct oral anticoagulant treatment? PMID- 25112676 TI - Chronic Stress Decreases Basal Levels of Memory-Related Signaling Molecules in Area CA1 of At-Risk (Subclinical) Model of Alzheimer's Disease. AB - An important factor that may affect the severity and time of onset of Alzheimer's disease (AD) is chronic stress. Epidemiological studies report that chronically stressed individuals are at an increased risk for developing AD. The purpose of this study was to reveal whether chronic psychosocial stress could hasten the appearance of AD symptoms including changes in basal levels of cognition-related signaling molecules in subjects who are at risk for the disease. We investigated the effect of chronic psychosocial stress on basal levels of memory-related signaling molecules in area CA1 of subclinical rat model of AD. The subclinical symptomless rat model of AD was induced by osmotic pump continuous intracerebroventricular (ICV) infusion of 160 pmol/day Abeta1-42 for 14 days. Rats were chronically stressed using the psychosocial stress intruder model. Western blot analysis of basal protein levels of important signaling molecules in hippocampal area CA1 showed no significant difference between the subclinical AD rat model and control rat. Following six weeks of psychosocial stress, molecular analysis showed that subclinical animals subjected to stress have significantly reduced basal levels of p-CaMKII and decreased p-CaMKII/t-CaMKII ratio as well as decreased basal levels of p-CREB, total CREB, and BDNF. The present results suggest that these changes in basal levels of signaling molecules may be responsible for impaired learning, memory, and LTP in this rat model, which support the proposition that chronic stress may accelerate the emergence of AD in susceptible individuals. PMID- 25112677 TI - Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE? AB - Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating synaptic transmission in cholinergic neurons of both vertebrates and invertebrates. ACHE is also involved in the regulation of cell growth and morphogenesis during embryogenesis and regeneration acting through its non cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for investigating the mechanisms underlying tissue morphogenesis due to its high regenerative power. Here, we performed a comparative investigation of arm morphogenesis during adult arm regeneration and embryonic arm development which may provide insights on the conserved ACHE pathways. In this study, we cloned and characterized O. vulgaris ACHE, finding a single highly conserved ACHE hydrophobic variant, characterized by prototypical catalytic sites and a putative consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at the COOH-terminus. We then show that its expression level is correlated to the stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is localized in typical neuronal sites when adult-like arm morphology is established and in differentiating cell locations during the early stages of arm morphogenesis. This possibility is also supported by the presence in the ACHE sequence and model structure of both cholinergic and non-cholinergic sites. This study provides insights into ACHE conserved roles during processes of arm morphogenesis. In addition, our modeling study offers a solid basis for predicting the interaction of the ACHE domains with pharmacological blockers for in vivo investigations. We therefore suggest ACHE as a target for the regulation of tissue morphogenesis. PMID- 25112678 TI - Complexin-1 and Foxp1 Expression Changes Are Novel Brain Effects of Alpha Synuclein Pathology. AB - As the second most frequent neurodegenerative disorder of the aging population, Parkinson's disease (PD) is characterized by progressive deficits in spontaneous movement, atrophy of dopaminergic midbrain neurons and aggregation of the protein alpha-synuclein (SNCA). To elucidate molecular events before irreversible cell death, we studied synucleinopathy-induced expression changes in mouse brain and identified 49 midbrain/brainstem-specific transcriptional dysregulations. In particular complexin-1 (Cplx1), Rabl2a and 14-3-3epsilon (Ywhae) downregulation, as well as upregulation of the midbrain-specific factor forkhead box P1 (Foxp1) and of Rabgef1, were interesting as early mRNA level effects of alpha-synuclein triggered pathology. The protein levels of complexin-1 were elevated in midbrain/brainstem tissue of mice with A53T-SNCA overexpression and of mice with SNCA-knockout. The response of CPLX1 and Foxp1 levels to SNCA deficiency supports the notion that these factors are regulated by altered physiological function of alpha-synuclein. Thus, their analysis might be useful in PD stages before the advent of Lewy pathology. Because both alpha-synuclein and complexin-1 modulate vesicle release, our findings support presynaptic dysfunction as an early event in PD pathology. PMID- 25112680 TI - The Neuroprotection of Lysosomotropic Agents in Experimental Subarachnoid Hemorrhage Probably Involving the Apoptosis Pathway Triggering by Cathepsins via Chelating Intralysosomal Iron. AB - alpha-Lipoic acid-plus (LAP), an amine derivative of alpha-lipoic acid (LA), could protect cells against oxidant challenges via chelating intralysosomal iron. However, the application of LAP in experimental subarachnoid hemorrhage (SAH) is still not well known. This study was designed to evaluate the potential neuroprotection of LAP on the early brain injury (EBI) and the underlying mechanisms in a rat model of SAH. The SAH models were induced in Sprague-Dawley rats. LA and LAP were oral administration and lasted for 72 h once a day. The brain tissue samples were obtained for assay at 72 h after SAH. In experiment 1, we found that lysosome amounts in neurons decreased significantly in SAH group, and LAP (100 mg/kg) could stabilize lysosomal membrane markedly based on lysosomal-associated membrane protein-1 (LAMP-1) expression in neurons by immunofluorescence. Hence, the LAP dosages of 100 and 150 mg/kg were applied in experiment 2. Firstly, Western blot analysis showed that the protein levels of cathepsin B/D, caspase-3, Bax, ferritin, and heme-oxygenase-1 (HO-1) markedly increased after SAH, which were further confirmed by double immunofluorescence staining and reversed by LA and LAP treatments. In addition, LA and LAP also reduced oxidative stress and iron deposition in brain tissue. Furthermore, LA and LAP significantly ameliorated brain edema, blood-brain barrier injury, cortical apoptosis, and neurological behavior impairment induced by SAH. Finally, it is noteworthy that LAP exerted more significant effects than LA on these parameters as described above. LAP probably exerted neuroprotective effects via targeting lysosomes and chelating intralysosomal iron in EBI post-SAH in rats. PMID- 25112681 TI - Investigation of effect of 17alpha-ethinylestradiol on vigilin expression using an isolated recombinant antibody. AB - Vigilin, a highly conserved protein from yeast to mammals, is a multifunctional protein in eukaryotic organisms. One biological function of vigilin is to stabilize the expression level of vitellogenin (VTG). This study aimed to develop vigilin as a new estrogen-inducible biomarker that correlates with the widely applied estrogen-inducible biomarker VTG and expand the ability to detect it in various species. Here, a recombinant monoclonal antibody with high specificity against the conserved C-terminal region of vigilin from zebrafish (Danio rerio) was successfully isolated from a phage display antibody library and found to recognize vigilin proteins from multiple vertebrate species. The effect of 17alpha-ethinylestradiol (EE2) on vigilin expression in the liver of zebrafish and juvenile crucian carp (Carassius auratus) was investigated. Although vigilin mRNA was expressed in all tissues analyzed from male zebrafish, vigilin protein was detected exclusively in the testis of male zebrafish, as well as the liver of female zebrafish and juvenile crucian carp at a lower level without exposure to EE2. Significant induction of vigilin mRNA by exposure to EE2 was observed in the liver and testis of male zebrafish, even at a low dose of 6.25 ng/L (21.09 pmol/L). In Hela cells, the expression of vigilin coincided with high protein synthesis activity but not dose-dependently by EE2 exposure. Therefore, the recombinant antibody may be used as a detection tool to screen for mammalian cell lines or organs with estrogen-inducible expression of vigilin. PMID- 25112682 TI - Gene markers of generic Escherichia coli associated with colonization and persistence of Escherichia coli O157 in cattle. AB - Enterohemorrhagic Escherichia coli (EHEC) O157 are important foodborne pathogens whose major reservoir are asymptomatic cattle. There is evidence suggesting that nonpathogenic E. coli and bacteriophages in the gastro-intestinal tract can influence the pathogenicity of EHEC O157. The factors contributing to the onset and persistence of shedding EHEC O157 in cattle are not completely elucidated. This study used Bayesian network analysis to identify genetic markers of generic E. coli associated with shedding of EHEC O157 in cattle from data generated during an oral experimental challenge study in 4 groups of 6 steers inoculated with three different EHEC O157 strains. The quantification of these associations was accomplished using mixed effects logistic regression. The results showed that the concurrent presence of generic E. coli carrying the prophage marker R4-N and the virulence marker stx2 increased the odds of the onset of EHEC O157 shedding. The presence of prophage markers z2322 and X011C increased, while C1.N decreased the odds of shedding EHEC O157 two days later. A significant antagonist interaction effect between the presence of the virulence marker stx2 on the day of shedding EHEC O157 and two days before shedding was also found. In terms of the persistence of EHEC O157 shedding, the presence of prophage marker R4-N (OR=16, and 95% confidence interval (CI): 1.1, 252) was found to increase the odds of stopping EHEC O157 shedding, whereas prophage marker C1.N (OR=0.16, CI: 0.03, 0.7) and the enterohemolysin gene hly (OR=0.03, CI: 0.001, 0.8) were found to significantly decrease the odds of stopping EHEC O157 shedding. In conclusion, the study found that the presence of certain genetic markers in the generic E. coli genome can influence the pathogenicity of EHEC O157. PMID- 25112679 TI - Ceftriaxone Protects Astrocytes from MPP(+) via Suppression of NF-kappaB/JNK/c Jun Signaling. AB - Ceftriaxone has been shown to attenuate the dopaminergic neuron death and alleviate behavioral disorders in Parkinson's disease models via upregulation of glutamate transporter-1 (GLT-1) and decreases in extracellular glutamate. However, details of how this neuroprotection occurs are uncertain. We hypothesized that cytoprotection by ceftriaxone in astrocytes exposed to 1-methyl 4-phenylpyridinium (MPP(+)) involves suppression of the NF-kappaB/JNK/c-Jun signaling pathway. Here, we observed a protective effect of ceftriaxone in primary astrocytes exposed to MPP(+). Ceftriaxone enhanced glutamate uptake and promoted primary astrocyte viability after MPP(+) exposure. Ceftriaxone enhances glutamate uptake via upregulation of GLT-1 in the plasma membrane, and alleviates MPP(+)-induced neurotoxicity via suppression of NF-kappaB/JNK/c-Jun signaling. Collectively, our data offer evidence that increased expression and function of GLT-1 are involved in the protective mechanism of ceftriaxone in astrocytes exposed to MPP(+) in vitro, and we offer insight into the potential therapeutic role of ceftriaxone in treatment of Parkinson's disease. PMID- 25112683 TI - Subcellular neural probes from single-crystal gold nanowires. AB - Size reduction of neural electrodes is essential for improving the functionality of neuroprosthetic devices, developing potent therapies for neurological and neurodegenerative diseases, and long-term brain-computer interfaces. Typical neural electrodes are micromanufactured devices with dimensions ranging from tens to hundreds of micrometers. Their further miniaturization is necessary to reduce local tissue damage and chronic immunological reactions of the brain. Here we report the neural electrode with subcellular dimensions based on single crystalline gold nanowires (NWs) with a diameter of ~100 nm. Unique mechanical and electrical properties of defect-free gold NWs enabled their implantation and recording of single neuron-activities in a live mouse brain despite a ~50* reduction of the size compared to the closest analogues. Reduction of electrode dimensions enabled recording of neural activity with improved spatial resolution and differentiation of brain activity in response to different social situations for mice. The successful localization of the epileptic seizure center was also achieved using a multielectrode probe as a demonstration of the diagnostics potential of NW electrodes. This study demonstrated the realism of single-neuron recording using subcellular-sized electrodes that may be considered a pivotal point for use in diverse studies of chronic brain diseases. PMID- 25112685 TI - Green condensation reaction of aromatic aldehydes with active methylene compounds catalyzed by anion-exchange resin under ultrasound irradiation. AB - To realize a practical and green chemistry, two important challenges need to be addressed, namely the effective process for the activation of reaction and efficient, eco-friendly and robust chemical methods for the reaction conversion to target products via highly selective catalytic and reactions. Ultrasonic energy promotes the conversion process through its special cavitational effects. Combined with anion-exchange resin as a heterogeneous, reusable and efficient catalyst, Ultrasonic energy enhances the Knoevenagel condensation and leads to reduced reaction time at lower reaction temperature with less amounts of solvent and catalyst. PMID- 25112684 TI - Sensitivity of free radicals production in acoustically driven bubble to the ultrasonic frequency and nature of dissolved gases. AB - Central events of ultrasonic action are the bubbles of cavitation that can be considered as powered microreactors within which high-energy chemistry occurs. This work presents the results of a comprehensive numerical assessment of frequency and saturating gases effects on single bubble sonochemistry. Computer simulations of chemical reactions occurring inside a bubble oscillating in liquid water irradiated by an ultrasonic wave have been performed for a wide range of ultrasonic frequencies (213-1100kHz) under different saturating gases (O2, air, N2 and H2). For O2 and H2 bubbles, reactions mechanism consisting in 25 reversible chemical reactions were proposed for studying the internal bubble chemistry whereas 73 reversible reactions were taken into account for air and N2 bubbles. The numerical simulations have indicated that radicals such as OH, H, HO2 and O are created in the bubble during the strong collapse. In all cases, hydroxyl radical (OH) is the main oxidant created in the bubble. The production rate of the oxidants decreases as the driving ultrasonic frequency increases. The production rate of OH radical followed the order O2>air>N2>H2 and the order becomes more remarkable at higher ultrasonic frequencies. The effect of ultrasonic frequency on single bubble sonochemistry was attributed to its significant impact on the cavitation process whereas the effects of gases were attributed to the nature of the chemistry produced in the bubble at the strong collapse. It was concluded that, in addition to the gas solubility, the nature of the internal bubble chemistry is another parameter of a paramount importance that controls the overall sonochemical activity in aqueous solutions. PMID- 25112686 TI - Current or voltage? Another Shakespearean dilemma. PMID- 25112688 TI - Infection rates of Linguatula serrata nymphs in mesenteric lymph nodes from water buffaloes in North India. AB - The literature pertaining to prevalence of Linguatula serrata in large ruminants is limited. In abattoir survey, the infection rate of L. serrata in 1440 mesenteric lymph nodes collected from 480 buffaloes from North India was investigated. Results revealed 88 (18.3%) buffaloes and 288 (20.0%) mesenteric lymph nodes having parasite's nymphs. Nonsignificant difference (P>0.05), between 1 and 3 years age (51.5%) and above three years of age (48.5%) groups was observed. Nonsignificant difference (P>0.05) between the infection rate of male (51.5%) and female (48.5%) was also observed. Infection in haemorrhagic (57.2%) and black-coloured (67.5%) nymph nodes were significantly (P<0.05) higher than normal-coloured nodes (8.8%). When compared based on consistency, the results showed soft lymph nodes (61.3%) were significantly (P<0.05) more infected than normal (12.8%) and hard (30.0%) lymph nodes. The intensity of infection in normal, haemorrhagic and black lymph nodes were 1.81 +/- 0.21, 4.23 +/- 0.0.62 and 5.12 +/- 0.73, nymphs respectively. The mean numbers of parasites in haemorrhagic and black-coloured lymph nodes were significantly (P<0.0005) more than mean number of parasites in normal-coloured nodes. Again intensity of infection in normal, soft and hard lymph nodes was 2.31 +/- 0.18, 5.84 +/- 0.74 and 3.21 +/- 0.68, respectively. When compared based on lymph nodes consistency, the soft lymph nodes were significantly (P<0.0005) more severely infected than normal and hard ones. The study has generated some vital data about the prevalence of this underreported disease amongst the bubaline intermediate hosts along with important gross changes in the affected lymph nodes. PMID- 25112687 TI - Identification of new novel scaffold for Aurora A inhibition by pharmacophore modeling and virtual screening. AB - Aurora kinases belong to family of highly conserved serine/threonine protein kinases that are involved in diverse cell cycle events and play a major role in regulation of cell division. Abnormal expression of Aurora kinases may lead to cancer; hence, these are considered as a potential target in cancer treatment. In this research article, we identified three novel Aurora A inhibitors using modern computational tools. A four-point common 3D pharmacophore hypothesis of Aurora A (AurA) inhibitors was developed using a diverse set of 55 thienopyrimidine derivatives. A three-dimensional quantitative structure-activity relationship (3D QSAR) study was carried out using atom-based alignment of diverse set of 55 molecules to evaluate the structure- activity relationships. Docking and 3D-QSAR studies were performed with the 3D structure of AurA to evaluate the generated pharmacophore. The pharmacophore model and 3D-QSAR results complemented the results of our docking study. The pharmacophore hypothesis, which yields the best results, was used to screen the Zinc 'clean drug-like' database. Various database filters such as 3D-arrangement of pharmacophoric features, predicted activity and binding interaction score were used to retrieve hits having potential AurA inhibition activity. PMID- 25112689 TI - Membrane disruptive antimicrobial activities of human beta-defensin-3 analogs. AB - Human beta defensin-3 (HbetaD-3) is a host-defense protein exhibiting antibacterial activity towards both Gram-negative and Gram-positive bacteria. There is considerable interest in the function of this protein due to its increased salt tolerance and activity against Gram-positive Staphylococcus aureus. In this study, analogs of HbetaD-3 devoid of N and C terminal regions are investigated to determine the influence of specific structural motif on antimicrobial activity and selectivity between Gram-positive and Gram-negative bacteria. Circular dichroism, fluorescence and solid-state NMR experiments have been used to investigate the conformation and mode of action of HbetaD3 analogs with various model membranes to mimic bacterial inner and outer membranes and also mammalian membranes. Our studies specifically focused on determining four major characteristics: (i) interaction of HbetaD3 analogs with phospholipid vesicles composed of zwitterionic PC or anionic PE:PG vesicles and LPS; (ii) conformation of HbetaD3-peptide analogs in the presence of PC or PE:PG vesicles; (iii) ability of HbetaD3 analogs to permeate phospholipid vesicles composed of PC or PE:PG; and (iv) activities on bacteria cells and erythrocytes. Our results infer that the linear peptide L25P and its cyclic form C25P are more active than L21P and C21P analogs. However, they are less active than the parent peptide, thus pointing towards the importance of the N terminal domain in its biological activity. The variation in the activities of L21P/C21P and L25P/C25P also suggest the importance of the positively charged residues at the C terminus in providing selectivity particularly to Gram-negative bacteria. PMID- 25112691 TI - Anthropometric indices are not satisfactory predictors of metabolic comorbidities in obese children and adolescents. AB - OBJECTIVE: To assess the accuracy of body mass index (BMI), Z score of the BMI, waist circumference, and waist-to-height ratio in selecting obese children with fasting metabolic impairments or impaired glucose tolerance. STUDY DESIGN: In a cohort of 883 obese children and adolescents (age 8-18 years), we assessed the associations of anthropometric indices with traditional metabolic complications of obesity (impaired fasting glucose, impaired glucose tolerance, hypertension, high triglycerides, low high-density lipoprotein-cholesterol). The accuracy of anthropometric indices as markers of metabolic impairment was assessed by receiver operating characteristic analysis and the areas under the receiver operating characteristics curves (AUROCs) of anthropometric indices were compared with each other by the DeLong test. RESULTS: BMI, Z score of the BMI, waist circumference, and waist-to-height ratio were associated with metabolic impairments but showed low to moderate accuracy in discriminating both single and clustered metabolic impairments. The AUROCs ranged from 0.55-0.70. The 4 anthropometric indices did not show significantly different AUROCs as predictors of clustered metabolic risk factors (all P values of DeLong tests: >.05). CONCLUSIONS: Commonly used anthropometric indices are not satisfactory markers of metabolic comorbidity among obese children and adolescents and should not be adopted as screening tools for the metabolic assessment of this category of patients. PMID- 25112690 TI - Conformational studies of chiral D-Lys-PNA and achiral PNA system in binding with DNA or RNA through a molecular dynamics approach. AB - The growing interest in peptide nucleic acid (PNA) oligomers has led to the development of a very wide variety of PNA derivatives. Among others, the introduction of charged chiral groups on a PNA oligomer has proven effective in improving DNA binding ability, complexation direction and cellular uptake. In particular, the introduction of three adjacent chiral monomers based on D-Lys in the middle of the PNA sequence (D-Lys-PNA) has produced noteworthy results in modulating the directionality of the binding with the DNA complementary strand and in mismatch detection. Here, through a molecular dynamics approach, a comparative study has been carried out to investigate the structural properties that drive the interaction of the chiral D-Lys-PNA and the corresponding achiral PNA system with DNA as well as RNA complementary strands, starting from the crystal structure of D-Lys-PNA in complex with DNA. The results obtained complement experimental data and indicate that the binding with the RNA molecule, compared to DNA, is differently affected by the addition of three D-Lys groups on the PNA backbone, suggesting that this modification could be taken into account for the development of new PNA-based molecules able to discriminate between DNA and RNA. PMID- 25112692 TI - Association of Clostridium difficile infections with acid suppression medications in children. AB - OBJECTIVE: Multiple studies have confirmed associations between acid suppression medication and Clostridium difficile infections (CDIs) in adults. Therefore, we sought to evaluate an association between acid suppression medications and CDI in children. STUDY DESIGN: A retrospective self-controlled case series was performed utilizing billing records from the TRICARE Management Activity military health system database. Children ages 2-18 years from October 1, 2001 to July 31, 2013, who had an outpatient or inpatient record of CDI diagnosis were included. The relative incidences (RIs) of CDI or recurrent CDI were calculated comparing time periods prescribed and not prescribed proton pump inhibitors (PPIs) or histamine 2 receptor antagonists (H2RAs). RESULTS: There were 2531 cases of CDI among 2437 patients, and 1190 (48.8%) were prescribed acid suppression medications. CDI were more likely to occur during periods when patients were prescribed a PPI (RI 2.36; 95% CI 2.22-2.52), H2RA (RI 1.95; 95% CI 1.63-2.34), or during periods while prescribed both simultaneously (RI 2.40; 95% CI 1.90-3.04). There were 265 (10.4%) cases that were classified as recurrent among 217 (8.9%) patients. Recurrent CDI also was found to be more likely during prescription periods of PPI (RI 1.74; 95% CI 1.51-2.00) and H2RA (RI 2.63; 95% CI 1.89-3.66). CONCLUSIONS: Acid suppression medications are associated with an increased risk of CDI and recurrent CDI. Judicious use of acid suppression medication should be considered, especially among those at highest risk for CDI. PMID- 25112693 TI - Factors affecting the natural decay of hepatitis B surface antigen in children with chronic hepatitis B virus infection during long-term follow-up. AB - OBJECTIVE: To investigate the factors predicting spontaneous clearance of hepatitis B surface antigen (HBsAg) in a long-term, prospectively followed cohort from childhood into adult life. STUDY DESIGN: Children with chronic hepatitis B virus (HBV) infection without treatment were followed longitudinally every 6 months. At each visit, liver profiles and HBV markers were assessed. Hepatitis B vaccination history and the maternal HBV markers also were studied. RESULTS: A total of 349 children (205 male) were followed for 20.6 +/- 4.4 years with initial ages of 8.4 +/- 3.9 years; 42 (12.0%) cleared HBsAg spontaneously. The HBsAg titers decayed with age, with an average annual clearance rate of 0.58%. Children had a lower annual HBsAg decay rate if their mothers are HBsAg carriers (P < .001). Hepatitis B e antigen-seroconversion is a favorable predictor for spontaneous HBsAg clearance (P = .04). Those with HBsAg titer <=1000 IU/mL at enrollment during childhood have a higher rate of HBsAg clearance (hazard ratio = 5.23; P < .001). Using HBsAg titer <=1000 IU/mL to predict HBsAg clearance, the sensitivity is 38.1%, specificity is 90.6%, positive predictive value is 35.6%, and negative predictive value is 91.4%. CONCLUSIONS: During long-term follow-up, spontaneous HBsAg clearance is most likely to occur in a patient born to a non HBsAg-carrier mother, is a hepatitis B e antigen-seroconverter, and had an initial HBsAg level <=1000 IU/mL. PMID- 25112694 TI - Heart rate variability and cardiovascular risk factors in adolescent boys. AB - OBJECTIVE: To establish reference values of heart rate variability (HRV) measures in a cohort of adolescent boys and to determine the relationship between HRV and the clustering of risk factors (RFs) for cardiovascular disease. STUDY DESIGN: This cross-sectional study included 1152 adolescent boys (age: 16.6 +/- 1.2 years old). Demographic data, health-related habits, obesity indicators, and blood pressure were evaluated. HRV measures of time (SD of all RR intervals, root mean square of the squared differences between adjacent normal RR intervals, and the percentage of adjacent intervals over 50 ms) and frequency domains were assessed (low [LF] and high [HF] frequency). RESULTS: The components of HRV were RR interval (827 +/- 128 ms), SD of all RR intervals (61.9 +/- 23.5 ms), root mean square of the squared differences between adjacent normal RR intervals (54.5 +/- 29.4 ms), percentage of adjacent intervals over 50 ms (29.4 +/- 20.4%), LF (53 +/ 16 nu), HF (47 +/- 16), and LF/HF (1.44 +/- 1.08). Greater sympathetic and lower parasympathetic modulation at rest were associated with higher adiposity, higher blood pressure and physical inactivity. Adolescents with 2 or more RFs also presented lower HRV than subjects with no RFs (P < .001). CONCLUSIONS: The study has provided descriptive indicators that help the interpretation of HRV results in adolescents. Lower HRV measures are associated with the clustering of cardiovascular RFs. PMID- 25112695 TI - Reliability of circulatory and neurologic examination by telemedicine in a pediatric intensive care unit. AB - OBJECTIVE: To test the hypothesis that telemedicine can reliably be used for many aspects of circulatory and neurologic examinations of children admitted to a pediatric intensive care unit (PICU). STUDY DESIGN: A prospective, randomized study in a 14-bed PICU in a tertiary care, academic-affiliated institution. Eligible patients were >2 months or <19 years of age, not involved in a concurrent study, had parents/guardian able to sign an informed consent form, were not at end-of-life, and had an attending who not only deemed them medically stable, but also felt that the study would not interrupt their care. Other than the Principal Investigator, 6 pediatric intensivists and 7 pediatric critical care fellows were eligible study providers. Two physician providers were randomly assigned to perform circulatory and neurologic examinations according to the American Heart Association/Pediatric Advanced Life Support guidelines in-person and via telemedicine. Findings were recorded on a standardized data collection form and compared. RESULTS: One hundred ten data collection forms were completed. For many aspects of the circulatory and neurologic examinations, outcomes showed substantial to perfect agreement between the in-person and telemedical care providers (kappa = 0.64-1.00). However, assessments of muscle tone had a kappa = 0.23, with a kappa = 0.37 for skin color. CONCLUSIONS: Telemedicine can reliably identify normal and abnormal findings of many aspects of circulatory and neurologic examinations in PICU patients. This finding opens the door to further studies on the use of telemedicine across other disciplines. PMID- 25112696 TI - Breech labour is not a particular indication for STAN monitoring. PMID- 25112698 TI - Classification of common variable immunodeficiencies using flow cytometry and a memory B-cell functionality assay. AB - BACKGROUND: The population of patients with common variable immunodeficiency (CVID) comprises a heterogeneous group of patients with different causes of hypogammaglobulinemia predisposing to recurrent infections, higher incidence of autoimmunity, and malignancy. Although memory B cells (memBcs) are key players in humoral defense and their numbers are commonly reduced in these patients, their functionality is not part of any current classification. OBJECTIVE: We established and validated a memBc enzyme-linked immunosorbent spot (ELISpot) assay that reveals the capacity of memBcs to develop into antibody-secreting cells and present an idea for a new classification based on this functional capacity. METHODS: The memBc ELISpot assay, combined with flow cytometry, was applied to patients with confirmed CVID in comparison with age-matched healthy control subjects. RESULTS: Ex vivo frequency of IgG-, IgM-, and IgA-secreting plasmablasts was significantly diminished by 27.2-, 2.4-, and 23.3-fold, respectively, compared with that seen in healthy control subjects. Moreover, in vitro differentiation of memBcs into antibody-secreting cells was 6.1-, 2.6-, and 3.7-fold significantly reduced for IgG-, IgM-, and IgA-secreting cells, respectively. Proliferation of memBcs correlates inversely to immunoglobulin secreting capacity, suggesting compensatory hyperproliferation. Furthermore, patients with no serum IgA can still have a detectable IgA ELISpot assay result in vitro. Most importantly, the large heterogeneity of memBc function in patients with CVID homogenously grouped by means of fluorescence-activated cell sorting allowed additional subclassification based on memBc/plasmablast function. CONCLUSION: These data suggest almost normal memBc/immunoglobulin-secreting plasmablast functionality in some patients if sufficient stimulatory signals are delivered, which might open up opportunities for new therapeutic approaches. PMID- 25112699 TI - IL-9 is a key component of memory TH cell peanut-specific responses from children with peanut allergy. AB - BACKGROUND: Differentiation between patients with peanut allergy (PA) and those with peanut sensitization (PS) who tolerate peanut but have peanut-specific IgE, positive skin prick test responses, or both represents a significant diagnostic difficulty. Previously, gene expression microarrays were successfully used to identify biomarkers and explore immune responses during PA immunotherapy. OBJECTIVE: We aimed to characterize peanut-specific responses from patients with PA, subjects with PS, and atopic children without peanut allergy (NA children). METHODS: A preliminary exploratory microarray investigation of gene expression in peanut-activated memory TH subsets from 3 children with PA and 3 NA children identified potential PA diagnostic biomarkers. Microarray findings were confirmed by using real-time quantitative PCR in 30 subjects (12 children with PA, 12 children with PS, and 6 NA children). Flow cytometry was used to identify the TH subsets involved. RESULTS: Among 12,257 differentially expressed genes, IL9 showed the greatest difference between children with PA and NA children (45.59 fold change, P < .001), followed by IL5 and then IL13. Notably, IL9 allowed the most accurate classification of children with PA and NA children by using a machine-learning approach with recursive feature elimination and the random forest algorithm. Skin- and gut-homing TH cells from donors with PA expressed similar TH2- and TH9-associated genes. Real-time quantitative PCR confirmed that IL9 was the highest differentially expressed gene between children with PA and NA children (23.3-fold change, P < .01) and children with PS (18.5-fold change, P < .05). Intracellular cytokine staining showed that IL-9 and the TH2-specific cytokine IL-5 are produced by distinct TH populations. CONCLUSION: In this study IL9 best differentiated between children with PA and children with PS (and atopic NA children). Mutually exclusive production of IL-9 and the TH2-specific cytokine IL-5 suggests that the IL-9-producing cells belong to the recently described TH9 subset. PMID- 25112697 TI - "Auto-anti-IgE": naturally occurring IgG anti-IgE antibodies may inhibit allergen induced basophil activation. AB - BACKGROUND: Naturally occurring IgE-specific IgG autoantibodies have been identified in patients with asthma and other diseases, but their spectrum of functions is poorly understood. OBJECTIVE: Address the hypothesis that: (i) IgG anti-IgE autoantibodies are detectable in the serum of all subjects but elevated in asthmatic patients regardless of atopic status as compared with controls; (ii) some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced basophil activation. METHODS: IgE-specific IgG autoantibodies were detected and quantified in sera using ELISA. Sera were examined for their ability to activate IgE-sensitized human blood basophils in the presence and absence of allergen using a basophil activation test, and to inhibit allergen binding to specific IgE on a rat basophilic cell line stably expressing human FcepsilonRI. RESULTS: IgG autoantibodies binding to both free and FcepsilonRI-bound IgE were detected in patients with atopic and non-atopic asthma, as well as controls. While some were able to activate IgE-sensitised basophils, others inhibited allergen-induced basophil activation, at least partly by inhibiting binding of IgE to specific allergen. CONCLUSION: Naturally occurring IgG anti-IgE autoantibodies may inhibit, as well as induce, basophil activation. They act in a manner distinct from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least partly explain why atopic subjects who make allergen-specific IgE never develop clinical symptoms, and why omalizumab therapy is of variable clinical benefit in severe atopic asthma. PMID- 25112700 TI - IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis. AB - BACKGROUND: In the respiratory mucosa, interleukin (IL)-33, has been shown to enhance T helper 2 (TH2)-type responses through the master regulatory gene GATA 3. IL-33 is upregulated in ulcerative colitis (UC), and the aim was to assess if IL-33 holds a similar key position in the shaping of the immune response in experimental colitis (piroxicam-accelerated colitis (PAC) in IL-10 (-/-) mice, dextran sodium sulfate (DSS) model) and UC. METHODS: Colonic IL-33 expression was determined in UC (8 active UC, 8 quiescent UC, and 7 controls) and experimental colitis. Mesenteric lymph node (MesLN) T cells were isolated from PAC IL-10 (-/-) mice and stimulated with IL-33. RESULTS: The colonic IL-33 expression was significantly upregulated all forms of colitis (P < 0.01) and correlated with disease severity score and inflammation (P < 0.001), and with GATA-3 expression levels (P < 0.01); no correlation with the TH1-specific T-bet expression was observed. MesLN T cells stimulated with IL-33 had increased GATA-3 expression, and showed an IL-33 dose-dependent increase in secreted TH2-type cytokines, whereas this effect was abolished by blocking IL-33 signaling. The non-TH2-type cytokine IL-17 was upregulated by IL-33 but in a T cell receptor dependent manner, as opposed to TH2-type cytokines, which required only IL-33 stimulation. CONCLUSIONS: The study demonstrates that intestinal IL-33 is capable of inducing GATA-3 in mucosal T cells, and suggests that IL-33 is a key mediator of pathological TH2 and non-TH2-type responses in intestinal inflammation. Blocking IL-33 signaling could be a feasible option in the treatment of UC. PMID- 25112702 TI - Declining trends in alcohol consumption among Swedish youth-does the theory of collectivity of drinking cultures apply? AB - AIMS: To analyse trends in alcohol consumption among young people in Sweden between 2004 and 2012, to test whether the theory of collectivity of drinking cultures is valid for a population of young people and to investigate the impact of an increasing proportion of abstainers on the overall per capita trends. METHODS: Data were drawn from an annual survey of a nationally representative sample of students in year 11 (17-18 years old). The data covered 9 years and the total sample comprised 36,141 students. Changes in the overall per capita consumption were tested using linear regression on log-transformed data, and changes in abstention rates were tested using logistic regression. The analyses were then continued by calculating average consumption in deciles. RESULTS: Alcohol consumption among year 11 students declined significantly among both boys and girls between 2004 and 2012. These changes were reflected at all levels of consumption, and the same results were found when abstainers were excluded from the analyses. The increasing proportion of abstainers had a minimal effect on the overall decline in consumption; rather, this was driven by a decline in consumption among the heaviest drinkers. CONCLUSION: The theory of collectivity of drinking cultures seems valid for understanding changes in alcohol consumption among Swedish year 11 students. No support was found for a polarization of alcohol consumption in this nationally representative sample. PMID- 25112703 TI - Comment on Rezen et al. Expression changes in human skeletal muscle miRNAs following 10 days of bed rest in young healthy males. Acta Physiol 2014; 210: 655 666. PMID- 25112701 TI - Overexpression and gene amplification of EGFR, HER2, and HER3 in biliary tract carcinomas, and the possibility for therapy with the HER2-targeting antibody pertuzumab. AB - BACKGROUND: Pertuzumab is a humanized monoclonal antibody that binds to HER2 at an epitope that prevents HER2 from dimerizing with ligand-activated HER-family receptors. To assess the potential of pertuzumab as a new therapy, the expression status of HER family members was determined in biliary tract carcinoma (BTC), and the antitumor activity of pertuzumab was investigated by assessing the inhibition of BTC cell growth. METHODS: The expression status of HER family members in 113 archival specimens of BTC was analyzed by using immunohistochemistry and fluorescence in situ hybridization. Using ten BTC cell lines, heregulin-alpha (HRG-alpha) stimulated cell proliferation and its inhibition by pertuzumab was tested in vitro. The phosphorylated HER family proteins and their respective downstream molecules were analyzed. In vivo antitumor activity of pertuzumab was evaluated in a xenograft model. RESULTS: Protein overexpression of HER2 and/or HER3 was observed in 23-34 % of the specimens and gene amplification in 17-27 %. Seven of the ten cell lines showed HER2 and/or HER3 protein overexpression and gene amplification, and HRG-alpha stimulated cell proliferation was observed in four of the ten cell lines. In a BTC cell line co-overexpressing HER2 and HER3, pertuzumab potently inhibited the HRG-alpha stimulated cell proliferation in a dose-dependent manner, and completely blocked the phosphorylation of HER3. Suppression of downstream pathway molecules including p-AKT was also observed. Pertuzumab inhibited the in vivo growth of subcutaneous tumors, and increased the number of apoptotic cancer cells. CONCLUSIONS: Pertuzumab exerts potent antitumor activity in BTC cells co-overexpressing HER2 and HER3. Pertuzumab provides a new therapeutic option against BTC. PMID- 25112704 TI - Endocrine disrupting potential of fipronil and its metabolite in reporter gene assays. AB - There is a rising concern about the ecological safety and potential health risks caused by pesticides that are commonly present in the environment. Previous studies have shown that metabolites of pesticides sometimes possess more potent endocrine activity than the parent compounds. However very little efforts had been devoted to evaluate the environmental risks of pesticide metabolites. In the present study, we evaluated the agonistic and antagonistic activities of fipronil and its metabolite, fipronil sulfone, and compared by in vitro reporter gene assays using CHO-K1 cells. For estrogenic and antiestrogenic activities, both fipronil and fipronil sulfone showed no agonistic activities but exhibited the similarly antagonistic activities via estrogen receptor alpha (ERalpha), with the RIC20 of 6.4 * 10(-7)M and 9.8 * 10(-7)M, respectively. In the thyroid hormone receptor (TR) assay, only fipronil sulfone showed anti-thyroid hormone activity with the RIC20 of 8.2 * 10(-7)M. Furthermore, molecular docking was employed to support the results in TR assay with lower MolDock score for fipronil sulfone. Data provided here suggested that it is of great significance to study the endocrine-disrupting effects of pesticide's metabolites, especially those with persistence in environment and high toxicity to non-targeted organisms. PMID- 25112705 TI - AChE inhibition: one dominant factor for swimming behavior changes of Daphnia magna under DDVP exposure. AB - As a key enzyme that hydrolyzes the neurotransmitter acetylcholine in cholinergic synapses of both vertebrates and invertebrates, acetylcholinesterase (AChE) is strongly inhibited by organophosphates. AChE inhibition may induce the decrease of swimming ability. According to previous research, swimming behavior of different aquatic organisms could be affected by different chemicals, and there is a shortage of research on direct correlation analysis between swimming behavior and biochemical indicators. Therefore, swimming behavior and whole-body AChE activity of Daphnia magna under dichlorvos (DDVP) exposure were identified in order to clarify the relationship between behavioral responses and AChE inhibition in this study. In the beginning, AChE activity was similar in all treatments with the control. During all exposures, the tendency of AChE activity inhibition was the same as the behavioral responses of D. magna. The AChE activity of individuals without movement would decrease to about zero in several minutes. The correlation analysis between swimming behavior of D. magna and AChE activity showed that the stepwise behavioral response was mainly decided by AChE activity. All of these results suggested that the toxicity characteristics of DDVP as an inhibitor of AChE on the swimming behavior of organisms were the same, and the AChE activity inhibition could induce loss of the nerve conduction ability, causing hyperactivity, loss of coordination, convulsions, paralysis and other kinds of behavioral changes, which was illustrated by the stepwise behavioral responses under different environmental stresses. PMID- 25112707 TI - NHS staff will treat civilians injured in Gaza. PMID- 25112706 TI - Sex-specific effects of long-term exposure to bisphenol-A on anxiety- and depression-like behaviors in adult mice. AB - Humans are routinely exposed to low levels of bisphenol A (BPA), an environmental endocrine disruptor, which is widely used in the production of polycarbonate plastics. The effects of perinatal exposure to BPA have been shown to affect various aspects of social behaviors such as anxiety and depression in adult offspring. Because sex hormones play a critical role in neurobehavior in adulthood, it is possible that long-term exposure to BPA has widespread effects on these emotional behaviors in adulthood. In the present study, adult mice were exposed to BPA at dosages of 0.04, 0.4, 4, 40 mg kg(-1)d(-1) for 12 weeks. A behavioral assay was performed using the open field test (OFT), mirrored maze, the elevated plus maze (EPM), and the forced swim task. The results showed that, after exposure to BPA at 0.4-40 mg kg(-1)d(-1), the number of open arm entries and the time spent in them in the elevated plus maze task were reduced in males but increased in females, and thus eliminating or reversing sex differences in these behaviors. BPA at 0.04-40 mg kg(-1)d(-1) increased the immobility of male mice in the forced swimming test. Furthermore, BPA (0.4-40 mg kg(-1)d(-1)) significantly decreased brain level of testosterone in males, but no significant influence was found in serum and the brain levels of estradiol in females. Western blot analysis further indicated that BPA at 0.4, 4, or 40 mg kg(-1)d(-1) significantly down-regulated the protein level of estrogen receptor beta (ERbeta) in the hippocampus of the adult males but not females, and inhibited the protein level of GABA(A)alpha2 receptor in hippocampus of males but promoted that of females. These results suggest that long-term exposure to BPA sex specifically affects anxiety- and depression-like behaviors in adult mice. Changes in the levels of GABA(A)alpha2 receptor and ERbeta proteins of hippocampus might be associated with BPA-induced changes in these emotional behaviors. PMID- 25112708 TI - Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression. AB - BACKGROUND: The molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI-responsive oesophageal eosinophilia (PPI-REE) and eosinophilic oesophagitis (EoE) remain unknown. AIM: To compare symptom-histological and cytokine gene expression in PPI-REE and EoE patients, at baseline and after specific treatment. METHODS: In consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene expression of eotaxin-3, IL-13, and IL-5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI-REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids. RESULTS: Fifty three patients were re-evaluated on PPI therapy. 23 patients (43%) had PPI-REE and 30 patients (57%) had EoE. At baseline, eotaxin-3/IL-13/IL-5 gene expression was indistinguishable between EoE and PPI-REE, excepting increased IL-5 expression in proximal oesophagus (12.54 vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin-3/IL-13 in PPI REE, at both oesophageal sites (P <= 0.008), and IL-5 in distal (P = 0.016), but not in proximal oesophagus. Patients with steroid-responsive EoE also showed a significant decrease in eotaxin-3/IL-5 expression at both oesophageal sites. In EoE patients, initial PPI trial significantly decreased distal oesophageal eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in 16%, but did not influence Th2 markers. CONCLUSIONS: Baseline cytokine gene expression in PPI-REE was nearly indistinguishable from EoE. PPI therapy significantly downregulated oesophageal eotaxin-3/Th2-cytokine gene expression in PPI-REE, similarly to that seen in steroid-responsive EoE. A subset of EoE patients showed clinicohistological improvement on PPI therapy. PMID- 25112709 TI - Prognostic implication of intratumoral metabolic heterogeneity in invasive ductal carcinoma of the breast. AB - BACKGROUND: The purpose of this study was to evaluate the prognostic implication of findings of intratumoral metabolic heterogeneity on pretreatment (18)F-FDG PET/CT scans in patients with invasive ductal carcinoma (IDC) of the breast. METHODS: One hundred and twenty-three female IDC patients who underwent pretreatment 18F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) scans were retrospectively evaluated in this study. The heterogeneity factor (HF) defined as the derivative (dV/dT) of a volume threshold function from 40% to 80%, was computed for each primary tumor. Other metabolic PET parameters (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were measured. The HF was compared with clinicopathologic factors and other PET parameters. Univariate and multivariate analyses for the overall survival (OS) were performed. RESULTS: The HF ranged from 0.02 to 6.72 (mean, 0.35 +/- 0.82) and significantly correlated with MTV (r = 0.955; p < 0.0001) and TLG (r = 0.354; p = 0.0001). The HF was significantly higher (implying more heterogeneity) in tumors with higher T and N stages. The optimal cut-off values for the OS determined using a receiver operating characteristic (ROC) curve were 0.34 for the HF, 5.6 for SUVmax, 8.55 cm(3) for MTV, and 14.43 for TLG. The OS rate among the 123 patients was 86.2%. T stage (1, 2 vs. 3, 4), N stage (0, 1 vs. 2, 3), M stage (0 vs. 1), ER status (+ vs. -), SUVmax (<= 5.6 vs. > 5.6), MTV (<= 8.55 cm(3) vs. > 8.55 cm(3)), TLG (<= 14.43 vs. > 14.43), and HF (< 0.34 vs. >= 0.34) affected the OS on univariate analysis. After adjustment for the effects of TNM stage and ER status, the HF and MTV were significant predictors of OS. Among the PET parameters, the best prognostic factor for OS was the HF. CONCLUSIONS: Intratumoral metabolic heterogeneity correlated closely with the MTV and significantly affected the OS in IDC patients. The HF may act as a robust surrogate marker for the prediction of OS in IDC patients. PMID- 25112711 TI - Nociceptive neurons regulate innate and adaptive immunity and neuropathic pain through MyD88 adapter. PMID- 25112712 TI - An ingredient for the elixir of youth. AB - Emerging evidence indicates that there are factors within the blood of young animals that have the ability to restore youthful characteristics to a number of organ systems in older animals. Growth/differentiation factor 11 (GDF11) is the first of such factors to be identified, and two new studies demonstrate that this "factor of youth" rejuvenates stem cells found in the skeletal muscle and brain of aged mice. PMID- 25112714 TI - FNDC5 could be regulated by leptin in adipose tissue. AB - INTRODUCTION: Irisin activates the thermogenic function in adipose tissues. However, little is known on the association between human irisin and different cardiometabolic risk factors. We analyse the influence of morbid obesity on irisin levels and its relation with leptin and different cardiovascular risk factors. MATERIAL AND METHODS: We measured the serum irisin level and the fibronectin type III domain containing 5 (FNDC5) expression in adipose tissue from 33 morbidly obese subjects and 12 nonobese subjects. We also studied the effect of leptin on FNDC5 expression. RESULTS: Serum irisin was higher in the nonobese subjects than in morbidly obese subjects, both before (P = 0.043) and after bariatric surgery (P = 0.042). The variable that best explained the serum irisin levels in a multiple linear regression model was the waist-to-hip ratio (WHR) (R(2) = 0.201) (Beta = -0.357, P = 0.046). Those morbidly obese subjects with android-type obesity had lower serum irisin levels than those with gynecoid type obesity, both before (P = 0.027) and after bariatric surgery (P = 0.006). Only the percentage change in WHR was associated with serum irisin levels after bariatric surgery (r = -0.529, P = 0.005). FNDC5 expression levels in subcutaneous adipose tissue (SAT) were higher in the nonobese than in the morbidly obese subjects (P = 0.042). In SAT explants from nonobese subjects, leptin (20 and 150 ng/mL) produced a decrease in FNDC5 expression (P = 0.009 and P = 0.037, respectively). CONCLUSIONS: We showed decreased serum irisin levels in morbidly obese subjects, related mainly to WHR. FNDC5 expression could be regulated by leptin. PMID- 25112715 TI - Structurally enhanced incremental neural learning for image classification with subgraph extraction. AB - In this paper, a structurally enhanced incremental neural learning technique is proposed to learn a discriminative codebook representation of images for effective image classification applications. In order to accommodate the relationships such as structures and distributions among visual words into the codebook learning process, we develop an online codebook graph learning method based on a novel structurally enhanced incremental learning technique, called as "visualization-induced self-organized incremental neural network (ViSOINN)". The hidden structural information in the images is embedded into the graph representation evolving dynamically with the adaptive and competitive learning mechanism. Afterwards, image features can be coded using a sub-graph extraction process based on the learned codebook graph, and a classifier is subsequently used to complete the image classification task. Compared with other codebook learning algorithms originated from the classical Bag-of-Features (BoF) model, ViSOINN holds the following advantages: (1) it learns codebook efficiently and effectively from a small training set; (2) it models the relationships among visual words in metric scaling fashion, so preserving high discriminative power; (3) it automatically learns the codebook without a fixed pre-defined size; and (4) it enhances and preserves better the structure of the data. These characteristics help to improve image classification performance and make it more suitable for handling large-scale image classification tasks. Experimental results on the widely used Caltech-101 and Caltech-256 benchmark datasets demonstrate that ViSOINN achieves markedly improved performance and reduces the computational cost considerably. PMID- 25112713 TI - Massive glycosaminoglycan-dependent entry of Trp-containing cell-penetrating peptides induced by exogenous sphingomyelinase or cholesterol depletion. AB - Among non-invasive cell delivery strategies, cell-penetrating peptide (CPP) vectors represent interesting new tools. To get fundamental knowledge about the still debated internalisation mechanisms of these peptides, we modified the membrane content of cells, typically by hydrolysis of sphingomyelin or depletion of cholesterol from the membrane outer leaflet. We quantified and visualised the effect of these viable cell surface treatments on the internalisation efficiency of different CPPs, among which the most studied Tat, R9, penetratin and analogues, that all carry the N-terminal biotin-Gly4 tag cargo. Under these cell membrane treatments, only penetratin and R6W3 underwent a massive glycosaminoglycan (GAG)-dependent entry in cells. Internalisation of the other peptides was only slightly increased, similarly in the absence or the presence of GAGs for R9, and only in the presence of GAGs for Tat and R6L3. Ceramide formation (or cholesterol depletion) is known to lead to the reorganisation of membrane lipid domains into larger platforms, which can serve as a trap and cluster receptors. These results show that GAG clustering, enhanced by formation of ceramide, is efficiently exploited by penetratin and R6W3, which contains Trp residues in their sequence but not Tat, R9 and R6L3. Hence, these data shed new lights on the differences in the internalisation mechanism and pathway of these peptides that are widely used in delivery of cargo molecules. PMID- 25112716 TI - Event-related complexity analysis and its application in the detection of facial attractiveness. AB - In this study, an event-related complexity (ERC) analysis method is proposed and used to explore the neural correlates of facial attractiveness detection in the context of a cognitive experiment. The ERC method gives a quantitative index for measuring the diverse brain activation properties that represent the neural correlates of event-related responses. This analysis reveals distinct effects of facial attractiveness processing and also provides further information that could not have been achieved from event-related potential alone. PMID- 25112717 TI - The role of the SST-thermocline relationship in Indian Ocean Dipole skewness and its response to global warming. AB - A positive Indian Ocean Dipole (IOD) tends to have stronger cold sea surface temperature anomalies (SSTAs) over the eastern Indian Ocean with greater impacts than warm SSTAs that occur during its negative phase. Two feedbacks have been suggested as the cause of positive IOD skewness, a positive Bjerknes feedback and a negative SST-cloud-radiation (SCR) feedback, but their relative importance is debated. Using inter-model statistics, we show that the most important process for IOD skewness is an asymmetry in the thermocline feedback, whereby SSTAs respond to thermocline depth anomalies more strongly during the positive phase than negative phase. This asymmetric thermocline feedback drives IOD skewness despite positive IODs receiving greater damping from the SCR feedback. In response to global warming, although the thermocline feedback strengthens, its asymmetry between positive and negative IODs weakens. This behaviour change explains the reduction in IOD skewness that many models display under global warming. PMID- 25112718 TI - Histamine impairs midbrain dopaminergic development in vivo by activating histamine type 1 receptors. AB - BACKGROUND: Histamine (HA) regulates the sleep-wake cycle, synaptic plasticity and memory in adult mammals. Dopaminergic specification in the embryonic ventral midbrain (VM) coincides with increased HA brain levels. To study the effect of HA receptor stimulation on dopamine neuron generation, we administered HA to dopamine progenitors, both in vitro and in vivo. RESULTS: Cultured embryonic day 12 (E12) VM neural stem/progenitor cells expressed transcripts for HA receptors H1R, H2R and H3R. These undifferentiated progenitors increased intracellular calcium upon HA addition. In HA-treated cultures, dopamine neurons significantly decreased after activation of H1R. We performed intrauterine injections in the developing VM to investigate HA effects in vivo. HA administration to E12 rat embryos notably reduced VM Tyrosine Hydroxylase (TH) staining 2 days later, without affecting GABA neurons in the midbrain, or serotonin neurons in the mid hindbrain boundary. qRT-PCR and Western blot analyses confirmed that several markers important for the generation and maintenance of dopaminergic lineage such as TH, Lmx1a and Lmx1b were significantly diminished. To identify the cell type susceptible to HA action, we injected embryos of different developmental stages, and found that neural progenitors (E10 and E12) were responsive, whereas differentiated dopaminergic neurons (E14 and E16) were not susceptible to HA actions. Proliferation was significantly diminished, whereas neuronal death was not increased in the VM after HA administration. We injected H1R or H2R antagonists to identify the receptor responsible for the detrimental effect of HA on dopaminergic lineage and found that activation of H1R was required. CONCLUSION: These results reveal a novel action of HA affecting dopaminergic lineage during VM development. PMID- 25112720 TI - Post-fracture pharmacotherapy for women with osteoporotic fracture: analysis of a managed care population in the USA. AB - Pharmacologic therapy is recommended to reduce future fracture risk. We examined osteoporosis medications dispensed to older women after first fracture. Only 23 % received therapy during the first year post-fracture. Prior osteoporosis therapy, a prior osteoporosis diagnosis, and older age were good predictors of post fracture osteoporosis therapy. INTRODUCTION: Pharmacologic therapy is recommended after osteoporotic fracture to reduce future fracture risk. The objective of this retrospective study was to examine osteoporosis therapy dispensed to women post fracture. METHODS: We identified women >=50 years old in a large administrative claims database from 2003 to mid-2012 who were continuously enrolled 2 years before (baseline) and 1 year after first osteoporotic fracture. Exclusions were Paget's disease or malignant neoplasm. Pre- and post-fracture osteoporosis therapies (oral and parenteral) were assessed overall and by fracture site. RESULTS: A total of 47,171 women of mean (SD) age of 63 (10) years were eligible; fractures included 8 % hip, 17 % vertebral, 73 % non-hip/non-vertebral, and 3 % multiple fracture sites. Only 18 % received osteoporosis therapy within 90 days and 23 % within 1 year post-fracture. Overall, 19 % of women had a prior osteoporosis diagnosis; 20 % had received osteoporosis therapy during baseline. Of 37,649 (80 %) women without baseline therapy, only 9 % initiated pharmacologic therapy within 1 year. The adjusted odds ratio (OR) of therapy within 1 year post fracture was significantly greater for women who had received baseline osteoporosis therapy (versus none) and who had vertebral (OR 12.7, 95 % confidence interval (CI) 11.2-14.5), hip (15.2, 12.5-18.7), or non-hip/non vertebral fracture (34.4, 31.7-37.3). Other significant predictors included pre fracture osteoporosis diagnosis (1.6, 1.4-1.7) and older age (OR range, 1.3-1.7). Treatment adherence was significantly better among women with baseline osteoporosis diagnosis. CONCLUSIONS: The substantial post-fracture treatment gap represents an important unmet need for women with osteoporotic fractures. Fracture liaison or adherence programs could lead to improved post-fracture treatment rates. PMID- 25112721 TI - Effect of education intervention on the quality and long-term outcomes of root canal treatment in general practice. AB - AIM: To compare the technical quality and long-term outcomes of root canal treatment by general practitioners of a Swedish Public Dental Service, before and after an endodontic education including Ni-Ti rotary technique (NiTiR). METHODOLOGY: A random sample was compiled, comprising one root filled tooth from each of 830 patients, treated by 69 general practitioners participating in the education: 414 teeth root filled in 2002, pre-education, using primarily stainless steel instrumentation and filling by lateral compaction, and 416 teeth root filled post-education (2005), using mainly NiTiR and single-cone obturation. Follow-up radiographs taken in 2009 were evaluated alongside immediate post filling radiographs from 2002 to 2005. The density and length of the root fillings were registered. Periapical status was assessed by the Periapical Index (PAI), using two definitions of disease: apical periodontitis (AP) (PAI 3 + 4 + 5) and definite AP (PAI 4 + 5). Tooth survival was registered. Root fillings pre- and post-education were compared using chi-square and Fisher's exact tests. Crude extraction rates per 100 years were calculated for comparison of tooth survival. Explanatory variables (type of tooth, root filling quality, periapical status, marginal bone loss, type and quality of coronal restoration) in relation to the dependent variable (AP at follow-up) were analysed by multivariable logistic regression. RESULTS: Follow-up data were available for 229 (55%) of teeth treated pre- and 288 (69%) treated post-education: both tooth survival (P < 0.001) and root filling quality were significantly higher (P < 0.001) in the latter. However, there was no corresponding improvement in periapical status. Both pre- and post-education, root fillings with definite AP on completion of treatment had significantly higher odds of AP or definite AP at follow-up. For teeth treated post-education, inadequate root filling quality was significantly associated with AP at follow-up. CONCLUSIONS: Despite a higher tooth survival rate and a significant improvement in technical quality of root fillings after the education, there was no corresponding improvement in periapical status. PMID- 25112722 TI - Patient-reported outcomes in Crohn's disease: does race matter? PMID- 25112719 TI - Icariin may benefit the mesenchymal stem cells of patients with steroid associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study. AB - In this study, we found out a previously undefined function of icariin which restored the dynamic balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in patients with osteonecrosis of femoral head (ONFH) via ABCB1-promoter demethylation. These findings provided important information regarding potential implication of icariin targeting epigenetic changes for the treatment of steroid -associated ONFH. INTRODUCTION: Here, we investigated whether icariin can also exert a beneficial role in the reactivation of MSCs in the patients with steroid-associated ONFH via ABCB1-promoter demethylation. METHODS: Bone marrow was collected from the proximal femur in patients with steroid-associated ONFH (n = 20) and patients with new femoral neck fractures (n = 22), and then MSCs were isolated. We investigated cell viability, intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp) activity, the transcript levels of ABCB1 and oxidative stress-related genes, methylation extent at CpG islands of ABCB1 promoter, and osteogenic and adipogenic differentiation ability of MSCs from the femoral neck fractures group and from the steroid-associated ONFH group treated with or without icariin. RESULTS: We observed that MSCs from the steroid associated ONFH group showed reduced proliferation ability, elevated ROS level, depressed MMP, weakened osteogenesis, and enhanced adipogenesis while low P-gp activity, transcription level of ABCB1, and oxidative stress-related genes as well as aberrant CpG islands hypermethylation of ABCB1 were also noted in steroid associated ONFH group. Treatment with icariin obviously induced de novo P-gp expression, decreased oxidative stress, and promoted osteogenesis. CONCLUSION: Icariin may be a potential drug targeting epigenetic changes for the treatment of steroid-associated ONFH. PMID- 25112724 TI - Visualizing oil displacement with foam in a microfluidic device with permeability contrast. AB - Foam mobility control and novel oil displacement mechanisms were observed in a microfluidic device representing a porous media system with layered permeability. Foam was pre-generated using a flow-focusing microfluidic device and injected into an oil-wet, oil-saturated 2-D PDMS microfluidic device. The device is designed with a central fracture flanked by high-permeability and low permeability zones stratified in the direction of injection. A 1 : 1, 1% blend of alpha olefin sulfonate 14-16 (AOS) and lauryl betaine (LB) surfactants produced stable foam in the presence of paraffin oil. The oil saturation and pressure drop across the microfluidic device were measured as a function of time and the injected pore volume, indicating an increase in apparent viscosity for foam with an accompanying decrease in oil saturation. In contrast to the control experiments, foam was shown to more effectively mobilize trapped oil by increasing the flow resistance in the fracture and high-permeability zones and by diverting the surfactant solution into adjacent low-permeability zones. The foam was observed to separate into gas-rich and aqueous-rich phases depending on matrix permeability, suggesting that it is not appropriate to treat foam as a homogeneous dispersion of gas and liquid. PMID- 25112723 TI - The histological quality and adequacy of diminutive colorectal polyps resected using jumbo versus hot biopsy forceps. AB - BACKGROUND: Polypectomy with jumbo forceps (JF) and polypectomy with hot biopsy forceps (HBF) are still widely used techniques for removal of diminutive colorectal polyps (DCPs). JF may be more effective for the removal of DCPs because of their larger size. AIM: To evaluate the histological quality and adequacy of DCPs resected using JF compared with HBF. METHODS: One hundred and seventy-nine patients with 237 DCPs were included in this study. DCPs were removed using either JP or HBF. RESULTS: The tissue architecture was good in 29.9 % of the HBF group, in comparison with 90 % of the JF group (p < 0.001). No cautery damage or crash artifact was observed in 93.3 % of JF group and in 8.5 % of HBF group (p < 0.001). Moreover, there were statistically significant differences between the groups with regard to the high level of cautery damage or crush artifact (p < 0.001). The overall diagnostic quality of the specimens removed using JF was significantly better than that of the specimens removed by HBF (96 vs. 80 %, respectively, p < 0.001). There were statistically significant inverse associations between cautery damage or crush artifact and overall diagnostic quality of HBF and JF (r = -0.373, p < 0.001; r = -0.382, p < 0.001, respectively). Surgical margins were determined as negative in 87.5 % of the JF group and in 76.1 % of the HBF group (p = 0.022). A total of 80.8 % of the JF specimens and 30.8 % of the HBF specimens were well evaluated for two lateral and deep surgical margins (p < 0.001). CONCLUSION: JF was superior to HBF for histopathological interpretation and eradication of DCPs. PMID- 25112727 TI - Synthesis and evaluation of novel analogues of ripostatins. AB - Ripostatins are polyene macrolactones isolated from the myxobacterium Sorangium cellulosum. They exhibit antibiotic activity by inhibiting bacterial RNA polymerase (RNAP) through a binding site and mechanism that are different from those of current antibacterial drugs. Thus, the ripostatins serve as starting points for the development of new anti-infective agents with a novel mode of action. In this work, several derivatives of ripostatins were produced. 15 Desoxyripostatin A was synthesized by using a one-pot carboalumination/cross coupling. 5,6-Dihydroripostatin A was constructed by utilizing an intramolecular Suzuki cross-coupling macrolactonization approach. 14,14'-Difluororipostatin A and both epimeric 14,14'-difluororipostatins B were synthesized by using a Reformatsky type aldol addition of a haloketone, Stille cross-coupling, and ring closing metathesis. The RNAP-inhibitory and antibacterial activities are presented. Structure-activity relationships indicate that the monocyclic keto-ol form of ripostatin A is the active form of ripostatin A, that the ripostatin C5 C6 unsaturation is important for activity, and that C14 geminal difluorination of ripostatin B results in no loss of activity. PMID- 25112731 TI - Female fetus is associated with greater maternal insulin resistance in pregnancy. AB - AIM: To explore the hypothesis that female fetus is associated with greater maternal insulin resistance during pregnancy. METHODS: In a singleton pregnancy cohort study (n = 299), we compared maternal insulin resistance according to fetal sex, based on plasma biomarkers from a 50-g 1-h oral glucose tolerance test at 24-28 weeks gestation. The primary outcome was plasma glucose-to-insulin ratio. Other outcomes included plasma proinsulin-to-insulin ratio, and insulin, proinsulin, leptin, adiponectin and insulin-like growth factor I and II concentrations. RESULTS: After adjusting for maternal race, age, parity, education, pre-pregnancy BMI, smoking and alcohol use, history of gestational diabetes, and gestational age at blood sampling, plasma insulin concentrations were significantly higher (mean +/- sd: 66.4 +/- 50.5 vs. 51.0 +/- 46.1 mU/l; adjusted P = 0.001), and glucose-to-insulin ratios significantly lower (2.60 +/- 2.03 vs. 3.77 +/- 4.98 mg/dl/mU/l; adjusted P = 0.002) in women bearing a female vs those bearing a male fetus, despite similar glucose levels (116.4 +/- 27.2 vs. 117.0 +/- 31.9 mg/dl; adjusted P = 0.92).There were no significant differences in proinsulin-to-insulin ratios, or leptin, adiponectin, insulin-like growth factor I and insulin-like growth factor II concentrations by fetal sex. CONCLUSION: Female fetus may be associated with greater maternal insulin resistance during pregnancy. PMID- 25112726 TI - DNA damage accumulation and repair defects in acute myeloid leukemia: implications for pathogenesis, disease progression, and chemotherapy resistance. AB - DNA damage repair mechanisms are vital to maintain genomic integrity. Mutations in genes involved in the DNA damage response (DDR) can increase the risk of developing cancer. In recent years, a variety of polymorphisms in DDR genes have been associated with increased risk of developing acute myeloid leukemia (AML) or of disease relapse. Moreover, a growing body of literature has indicated that epigenetic silencing of DDR genes could contribute to the leukemogenic process. In addition, a variety of AML oncogenes have been shown to induce replication and oxidative stress leading to accumulation of DNA damage, which affects the balance between proliferation and differentiation. Conversely, upregulation of DDR genes can provide AML cells with escape mechanisms to the DDR anticancer barrier and induce chemotherapy resistance. The current review summarizes the DDR pathways in the context of AML and describes how aberrant DNA damage response can affect AML pathogenesis, disease progression, and resistance to standard chemotherapy, and how defects in DDR pathways may provide a new avenue for personalized therapeutic strategies in AML. PMID- 25112730 TI - Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts. AB - BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average particulate matter (PM(10), PM(2.5), PM(absorbance), PM(coarse)), NO(2), nitrogen oxides (NO(x)) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for >=3 months of the year for >=2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. RESULTS: 15 279 and 10 537 participants respectively were included in the main NO(2) and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO(2) and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PM(coarse) OR 1.31 (1.05 to 1.64) per 5 ug/m(3) increase and PM(10) with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM(2.5abs) (black carbon) exposures. CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations. PMID- 25112733 TI - First discovery of Quercus feeding Nepticulidae (Lepidoptera) in Central America. AB - Despite the high taxonomic diversity of oaks in Mexico and Central America, no Quercus feeding Nepticulidae have ever been recorded from the region. Here, we present seven species whose larvae are leaf-miners of Quercus (section Lobatae) in Guatemala. Except Stigmella nigriverticella (Chambers 1875), which was previously known from the United States, all other discovered species are new. We describe and name five new species (Stigmella jaguari Remeikis & Stonis, sp. nov., S. lauta Diskus & Stonis, sp. nov., S. sublauta Remeikis & Stonis, sp. nov., S. aurifasciata Diskus & Stonis, sp. nov. and S. guatemalensis Diskus & Stonis, sp. nov.); the remaining new species is described but left unnamed because of lack of adults (i. e. moths and genitalia are described from developed pupae). All seven treated species are illustrated with photographs of the leaf mines, adults, and genitalia. PMID- 25112732 TI - Lipocalin 2: a new mechanoresponding gene regulating bone homeostasis. AB - Mechanical loading represents a crucial factor in the regulation of skeletal homeostasis. Its reduction causes loss of bone mass, eventually leading to osteoporosis. In a previous global transcriptome analysis performed in mouse calvarial osteoblasts subjected to simulated microgravity, the most upregulated gene compared to unit gravity condition was Lcn2, encoding the adipokine Lipocalin 2 (LCN2), whose function in bone metabolism is poorly known. To investigate the mechanoresponding properties of LCN2, we evaluated LCN2 levels in sera of healthy volunteers subjected to bed rest, and found a significant time dependent increase of this adipokine compared to time 0. We then evaluated the in vivo LCN2 regulation in mice subjected to experimentally-induced mechanical unloading by (1) tail suspension, (2) muscle paralysis by botulin toxin A (Botox), or (3) genetically-induced muscular dystrophy (MDX mice), and observed that Lcn2 expression was upregulated in the long bones of all of them, whereas physical exercise counteracted this increase. Mechanistically, in primary osteoblasts transfected with LCN2-expression-vector (OBs-Lcn2) we observed that Runx2 and its downstream genes, Osterix and Alp, were transcriptionally downregulated, and alkaline phosphatase (ALP) activity was less prominent versus empty-vector transduced osteoblasts (OBs-empty). OBs-Lcn2 also exhibited an increase of the Rankl/Opg ratio and IL-6 mRNA, suggesting that LCN2 could link poor differentiation of osteoblasts to enhanced osteoclast stimulation. In fact, incubation of purified mouse bone marrow mononuclear cells with conditioned media from OBs-Lcn2 cultures, or their coculture with OBs-Lcn2, improved osteoclastogenesis compared to OBs-empty, whereas treatment with recombinant LCN2 had no effect. In conclusion, our data indicate that LCN2 is a novel osteoblast mechanoresponding gene and that its regulation could be central to the pathological response of the bone tissue to low mechanical forces. PMID- 25112735 TI - Redescription of five gnathiid species from Japan (Crustacea: Isopoda). AB - Five gnathiid species from Japan are redescribed based on14 holotypes, their paratypes, topotypes, and new materials. Observations of these specimens revealed that Caecognathia kikuchii (Nunomura, 1992) should be transferred to genus Elaphognathia and Caecognathia nasuta (Nunomura, 1992) to genus Gnathia. Furthermore, Caecognathia amakusaensis Nunomura, 1992, C. saikaiensis Nunomura, 1992, Gnathia azumai Nunomura, 2012a, G. quadricephala Nunomura, 2012a, and G. recticornata Nunomura, 2012a are considered to be junior synonyms of E. kikuchii. Gnathia hirayamai Nunomura, 1992, G. nagasakiensis Nunomura, 2012a, G. shijikiensis Nunomura, 2012a, and G. brevicephala Nunomura, 2012a are considered to be junior synonyms of G. nasuta. Moreover, Gnathia sanrikuensis Nunomura, 1998 and G. mutsuensis Nunomura, 2004 are redescribed. Gnathia bungoensis Nunomura, 1982 is not completely redescribed because the key characteristics were lacking. The geographical records of these species are provided. PMID- 25112734 TI - A new species-group of Chrysura Dahlbom, 1845 (Hymenoptera: Chrysididae), with description of Ch. baiocchii sp. nov. from Iran . AB - Chrysura baiocchii Rosa sp. nov. is described from Iran. Diagnosis of the new species-group Ch. baiocchii and discussions on Ch. radians group and Ch. genalis subgroup are given. PMID- 25112736 TI - New records of moth flies (Diptera: Psychodidae) from Croatia, with the description of Berdeniella keroveci sp.nov. AB - Berdeniella keroveci sp. nov. is described based on males collected in Croatia. Current knowledge of the psychodid fauna of Croatia is reviewed and new records of 16 species are presented. Short taxonomic notes on Pericoma pseudocalcilega Krek, 1972, Pneumia balkanica (Krek, 1990), Pneumia mutua (Eaton, 1893), Clogmia albipunctata (Williston, 1893) and Lepiseodina tristis (Meigen, 1810) are given. In total, 33 species of Psychodidae are known to occur in Croatia. PMID- 25112737 TI - A new species of Lixophaga Townsend (Diptera: Tachinidae) from Colombia, a parasitoid of Neoleucinodes elegantalis (Guenee) (Lepidoptera: Crambidae). AB - A new species of Lixophaga Townsend (Diptera: Tachinidae) from Colombia, Lixophaga puscolulo Carrejo & Woodley, sp. nov., is described and illustrated. It is a parasitoid of the tomato fruit borer, Neoleucinodes elegantalis (Guenee) (Lepidoptera: Crambidae), an insect pest of Solanum quitoense Lam., in Colombia. Aspects of its biology are briefly discussed. PMID- 25112738 TI - New species of the genus Jacekaphorura (Collembola: Onychiuridae) from upper reaches of Kolyma river (North-East of Russia). AB - Two new species of the genus Jacekaphorura from the North-East of Russia, viz. J. catherinae sp. nov. and J. furcata sp. nov., were described and illustrated. The former species clearly differs from the only previously known species of the genus by a high and variable number of dorsal pso, the latter can easily be distinguished due to specific structure of furcal remnant. The generic diagnosis and position within modern tribal subdivision of the Onychiurinae are discussed. PMID- 25112739 TI - A new species of Elathous Reitter (Coleoptera: Elateridae) from Turkey. AB - A new click-beetle species, Elathous serti, from Denizli and Isparta provinces of Turkey is described. Photographs of the adults, drawings of the aedeagi, a contrasting comparison table, a key to all Turkish Elathous species, a distribution map, and a table of collecting months and collecting provinces of all Turkish species are provided. PMID- 25112740 TI - Munidopsis lauensis Baba & de Saint Laurent, 1992 (Decapoda, Anomura, Munidopsidae), a newly recorded squat lobster from a cold seep in Taiwan. AB - The squat lobster, Munidopsis lauensis Baba & de Saint Laurent, 1992, is recorded from Taiwan for the first time. This species was previously known only from deep sea hydrothermal vents in the South-West Pacific but it was now found at a deep sea cold seep site off southwestern Taiwan. The identity of the Taiwanese material is confirmed by comparison of sequences from the barcoding gene COI. Munidopsis lauensis can be easily separated from other congeners in Taiwanese waters by the eyes bearing a strong mesiodorsal spine and a small mesioventral spine, smooth carapace, fingers of the cheliped distally spooned and fixed finger without a denticulate carina on the distolateral margin. The discovery of this species in Taiwan increases the Munidopsis fauna of the island to 38 species. A color photograph and line drawings illustrating distinctive characters are provided for the Taiwanese material. PMID- 25112741 TI - First description of the female Ozyptila kansuensis (Tang, Song & Zhu, 1995), comb. nov. (Araneae: Thomisidae) . PMID- 25112742 TI - Four new leaf-mining Acalyptris species from Guatemala and Belize, with new data on bionomics of Stigmella pruinosa (Lepidoptera: Nepticulidae). AB - This paper describes four new species: Acalyptris basicornis Remeikis & Stonis, sp. nov., A. peteni Diskus & Stonis, sp. nov., A. caribbicus Diskus & Stonis, sp. nov. (host-plant: Lantana involucrata L., Verbenaceae), and A. statuarius Diskus & Stonis, sp. nov. Another species, Stigmella pruinosa Puplesis & Robinson, is re described, with new distribution records in Guatemala and with the first documentation of leaf-mines on Guazuma ulmifolia Lam. (Malvaceae). All five species are illustrated with photographs of the leaf-mines, adults, and genitalia. PMID- 25112743 TI - Cuapetes yapiensis sp. nov. (Crustacea: Decapoda: Pontoniinae), a new mangrove shrimp from Yap, Caroline Islands. AB - A new pontoniine shrimp species, Cuapetes yapiensis, from mangroves at Quamun, on Yap Island, Caroline Islands, is described and illustrated. Cuapetes yapiensis most closely resembles C. darwiniensis Bruce. Six species of Cuapetes are now known from the Caroline Islands. PMID- 25112744 TI - New Mycomya species from the Himalayas (Diptera, Mycetophilidae): 3. Subgenera Cesamya and Mycomyopsis. AB - Mycomya Rondani specimens from the Himalayas, mostly Nepal and Myanmar, are revised. Altogether four species of the subgenus Cesamya Kocak & Kemal and eleven species of the subgenus Mycomyopsis Vaisanen are recorded from the Himalayas and the Indian subcontinent. The paper includes a key to the Himalayan species of Mycomya of the two subgenera. The following fourteen new species are described: M. aix, M. alticola, M. banteng, M. cissa, M. ducula, M. irena, M. goral, M. jeti, M. kaa, M. naja, M. niltava, M. pitta, M. sachak, and M. sanar. The holotype of M. unipectinata Edwards from Sri Lanka was also examined and its genitalia are described. PMID- 25112745 TI - Review of genus Nicephora Bolivar (Orthoptera, Tettigoniidae, Meconematinae). AB - This article presents a revision on all species of genus Nicephora Bolivar, 1900, describes 1 new species distribute in China ally to this genus. A key to species of the genus is given. PMID- 25112746 TI - Systematical studies on the species of the subgenus Bombus (Thoracobombus) (Hymenoptera: Apidae, Bombus Latreille) in Turkey. AB - The aim of this study was to analyze the 12 species which belong to the subgenus Bombus (Thoracobombus) by identifying, collating and testing the applicability of geometrics morphometrics for distinguishing the species. This was carried out on 133 females and 42 males which were collected from various localities in Turkey. After digitizing landmarks on the right fore wings, 2-dimensional Cartesian coordinates were calculated and by Procrustes analysis the coordinates were standardized and superimposed. Principal Components Analysis (PCA) and Canonical Variates Analysis (CVA) were performed to show the distribution of all species. Then, deformations which appeared in thin-plate splines were observed. Mean values of all the specimens were calculated and Sequential, Agglomerative, Hierarchical, and Nesting clustering method (SAHN) was performed with these data to obtain the dissimilarity trees. It can be concluded that all species were found to have consistently different wing shapes from each other. In females, the species B. armeniacus, B. mesomelas and B. pomorum which resemble each other, were also found to be similar based on their wing morphometry. Both in females and males, the subspecies B. sylvarum citrinofasciatus and B. sylvarum daghestanicus and the species B. humilis and B. laesus exposed high similarity in wing morphometry. In males, results showed that the species B. armeniacus and B. mesomelas and the species B. humilis and B. zonatus have very similar wing shape. PMID- 25112747 TI - A new name for the oviraptorid dinosaur "Ingenia" yanshini (Barsbold, 1981; preoccupied by Gerlach, 1957). AB - The genus name of the small oviraptorid dinosaur Ingenia yanshini is preoccupied by the tripyloidid nematode Ingenia mirabilis, thus making the former a junior homonym of the latter. Although "Ingenia" yanshini is sympatric with Conchoraptor gracilis, it is distinguished from Conchoraptor by proportions of the manus. It also differs appreciably from the ingeniines Heyuannia huangi and Nemegtomaia barsboldi in manual and pelvic proportions. "Ingenia" yanshini is not referable to any other taxon, and is renamed Ajancingenia yanshini gen. nov. Several specimens originally referred to this species have subsequently been transferred to new genera, and the taxonomic assignment of material referred to Ajancingenia yanshini gen. nov. is reassessed. PMID- 25112748 TI - Tanyproctus (Tanyproctus) arher (Coleoptera: Scarabaeidae: Melolonthinae: Tanyproctini), a new species from the Socotra Island, Yemen. AB - Tanyproctus (Tanyproctus) arher Bezdek, Sehnal & Kral, new species, is described from Socotra Island (Yemen), based on external morphology including male genitalia. PMID- 25112749 TI - The first description of adult female of Borboropactus asper (O. P.-Cambridge, 1884) from Sri Lanka (Araneae: Thomisidae). PMID- 25112750 TI - Description of new species of oak leaf-miners (Lepidoptera: Nepticulidae), with notes on the species groups of Stigmella Schrank associated with Quercus as a host-plant. AB - Stigmella acuta Diskus, Navickaite & Remeikis, sp. nov., a new species of oak feeding leaf-miner belonging to the S. hemargyrella group, and S. cornuta Rociene & Stonis, sp. nov., belonging to the newly designated S. cornuta group, are described from Asia and, for the first time, the S. hemargyrella group is associated with Quercus as a host-plant. The new species are illustrated with photographs of the leaf mines, adults, and genitalia. Diagnostics and host-plant preferences of seven Stigmella species groups associated with oaks (the S. caesurifasciella, S. saginella, S. quercipulchella, S. ruficapitella, S. castanopsiella, S. hemargyrella and S. cornuta groups) are discussed. PMID- 25112751 TI - Studies on the chorionic structure of the eggs of Corixoidea (Hemiptera: Heteroptera) with scanning electron microscopy. AB - The chorionic structure of the eggs of sixteen species of Corixoidea (Ectemnostega (Ectemnostega) quadrata (Signoret), E. (Ectemnostegella) quechua (Bachmann), Trichocorixa mendozana Jaczewski, Centrocorisa kollari (Fieber), Heterocorixa brasiliensis Hungerford, Sigara (Aphelosigara) tucma Bachmann, S. (Tropocorixa) denseconscripta (Breddin), S. (T.) platensis Bachmann, S. (T.) rubyae (Hungerford), S. (T.) santiagiensis (Hungerford), S. (T.) schadei (Hungerford), S. (T.) yala Bachmann, Tenagobia (Incertagobia) incerta Lundblad, T. (Fuscagobia) fuscata (Stal), T. (Schadeogobia) schadei Lundblad, and T. (Tenagobia) pulchra Hungerford) is described for the first time using scanning electron microscopy. In addition, the eggs of some of these species are described based on color and morphometry. The sculpturing of the chorion and the structure of the micropylar area here in studied using scanning electron microscopy together with the length of the stalk distinguish the eggs of the genera (except Sigara, genus without a uniform pattern on the sculpturing of the chorion) and subgenera (including Aphelosigara and Tropocorixa) of Corixoidea present in Argentina. The above mentioned characters, together with the egg length, proved to be useful for the identification of the Argentinian species. An identification key to the eggs of Argentinian species of Corixoidea based on the material herein studied, and additional data present in the literature, is provided. PMID- 25112752 TI - Four new species of genus Parallaxis McAtee (Hemiptera: Cicadellidae: Typhlocybinae: Dikraneurini) from Argentina, with a key to known species. AB - Four new species of Parallaxis McAtee are described from Argentina, P. jujuiensis sp. n., P. misionensis sp. n., P. tucumanensis sp. n. and P. virlai sp. n. Detailed morphological descriptions and illustrations of the new species and a key to males of known species are provided. PMID- 25112753 TI - Four new species of the genus Smaragdina Chevrolat, 1836 from China (Coleoptera: Chrysomelidae: Cryptocephalinae: Clytrini) . AB - Four new species are described for the genus Smaragdina, from Sichuan, Yunnan and Zhejiang provinces of China: Smaragdina tianmuensis sp. nov., S. yajiangensis sp. nov., S. yangae sp. nov., and S. zhangi sp. nov. The Chinese fauna of the genus is thus increased to 64 species. Color plates and line drawings of habitus, maxilla, labium, as well as those characters from the internal morphology like male genitalia, female spermatheca, and rectal sclerites are provided. PMID- 25112754 TI - Two new species of Tylototriton from Thailand (Amphibia: Urodela: Salamandridae). AB - Three morphological groups are found in a salamandrid newt Tylototriton shanjing from Thailand. We describe two of them as new species, one from northern and the other from northeastern Thailand, based on molecular and morphological data, however we could not make a taxonomic decision on the remaining one group because of the lack of voucher specimens and sufficient genetic data. The northern species differs morphologically from all known congeners by having the combination of orange to reddish brown markings, narrow and sharply protruding dorsolateral bony ridges on head, weakly segmented vertebral ridge, and long and high tail. The northeastern species is characterized by having the combination of yellow, orange, or reddish brown markings, wide and moderately protruding dorsolateral bony ridges on head, smooth vertebral ridge, black limbs, and black tail except for edges. Validity of taxonomic subdivision of the genus Tylototriton is discussed. PMID- 25112755 TI - Description of a new Tiger Snake (Colubridae, Telescopus) from south-western Africa. AB - Telescopus finkeldeyi sp. nov. is described from western central to northern Namibia and south-western Angola. Its maximum size is less than that of the other three taxa occurring in southern Africa. It is further distinguished by its fairly variable colour pattern. Although the number of ventrals and the undivided anal scale are similar to that of T. beetzii, the presence of 19 scale rows around the middle differs from the 21 rows of T. beetzii. PMID- 25112756 TI - Three new species of the genus Brachinus Weber, 1801 from the Philippines, with a modified key to species (Coleoptera: Carabidae: Brachininae). AB - Three new Brachinus species namely B. grootaerti n. sp. (Palawan Island), B. palawanensis n. sp. (Palawan Island), B. mindanaoensis n. sp. (Mindanao Island) from Philippines were described. In addition, a modified key to the known Brachinus Philippine species is provided. PMID- 25112757 TI - Loranthophila, a new genus of Australian Lyctinae (Coleoptera: Bostrichidae) associated with Mistletoe. AB - Loranthophila gen. n. is described, based on Minthea acanthacollis (Carter & Zeck), and comparisons are made between this genus and other members of the bostrichid subfamily Lyctinae. PMID- 25112758 TI - Annotated list of Tettigoniidae (Orthoptera) from the East Usambara Mountains, Tanzania and new Tettigoniidae species from East Africa. AB - A list of the Tettigoniidae (Orthoptera) of the East Usambara Mountains is presented and 16 new species are described from East Africa. A total number of 29 Tettigoniidae species is recorded for the East Usambara Mountains. New species are described from the Shimba Hills in Kenya, coastal Tanzania from the Kazimzumbwi forest reserve, Mt Kilimanjaro, the East and West Usambara and Uluguru Mountains in Tanzania, namely in Conocephalinae Afroagraecia pwania n. sp., Afroagraecia shimbaensis n. sp., Afroanthracites discolor n. sp., Afroanthracites jagoi n. sp. and Afroanthracites viridis n. sp., in Meconematinae Afrophisis flagellata n. sp., Afrophisis kisarawe n. sp., Afrophisis mazumbaiensis n. sp. and Afrophisis pseudoflagellata n. sp., in Hexacentrinae Aerotegmina megaloptera n. sp., in Mecopodinae Apteroscirtus cristatus n. sp., and A. planidorsatus n. sp., in Phaneropterinae Gelotopoia amabilis n. sp., and in Pseudophyllinae Cymatomerella pardopunctata n. sp. and Cymatomera viridimaculata n. sp. Seven species are endemic to the East Usambara Mountains which are 25% of the recorded forest-bound bush crickets. The Tettigoniidae fauna is compared between the East Usambara Mountains and Mt Kilimanjaro and mechanisms of speciation discussed in Orthoptera for the area. New Tettigoniidae records are given for Mt Kilimanjaro (Oxyecous apertus Ragge, Tropidonotacris grandis Ragge and Eurycorypha conclusa Hemp). PMID- 25112759 TI - Updated checklist of the ice-crawlers (Insecta: Grylloblattodea: Grylloblattidae) of North America, with notes on their natural history, biogeography and conservation. AB - We provide an updated checklist and comprehensive distributional record of Grylloblatta (Grylloblattodea: Grylloblattidae) in North America. These distribution records are based upon a thorough review of the literature, as well as unpublished data of the authors and colleagues. Thirteen species of Grylloblatta are currently described, with up to 16 additional taxa awaiting formal description. Distributional data shows that endemism of Grylloblatta is high and geographic range size is typically small: the median geographical area of 13 species and six putative species is 179 km2. It is clear that there is a general lack of knowledge of species range limits and local population sizes; for example, three Grylloblatta species are known from just a single locality and less than 15 specimens each. Conservation status ranks are suggested in order to update the IUCN Red List and national Natural Heritage Network Database. Finally, we describe the natural history and seasonality of Grylloblatta, discuss their unique biogeography, and provide recommendations for future surveys of grylloblattid species by highlighting known distributional gaps. PMID- 25112760 TI - Two new species of the genus Temnaspis Lacordaire, 1845, (Coleoptera: Chrysomeloidea: Megalopodidae) from China and Myanmar, with notes on the biology of the genus. AB - Two new species of the genus Temnaspis Lacordaire, 1845, family Megalopodidae, are described from China and Myanmar: Temnaspis puae Li & H.B. Liang, sp. nov., Temnaspis syringa Li & H.B. Liang, sp. nov. Biological notes are provided for Temnaspis syringa. Temnaspis flavicornis Jacoby, 1892 is redescribed and a lectotype designated. A key to species of the genus Temnaspis with black elytra in China and adjacent areas is provided. PMID- 25112761 TI - Phylogeny of the Cyrtodactylus irregularis species complex (Squamata: Gekkonidae) from Vietnam with the description of two new species. AB - The number of described species of bent-toed geckos of the Cyrtodactylus irregularis species complex in Vietnam has increased from one to eight in the last six years. We combined morphological and molecular analyses to explore phylogenetic relationships among all described species in the group. The phylogeny required the description of two new species, Cyrtodactylus phuocbinhensis sp. nov. and Cyrtodactylus taynguyenensis sp. nov. Further, the tree resolved two additional undescribed clades that may also be new species. The species C. bugiamapensis and C. ziegleri were found to require redefinition. Cyrtodactylus phuocbinhensis sp. nov. is characterized by a series of enlarged femoral scales separated from preanal scales while Cyrtodactylus taynguyenensis sp. nov. does not possess enlarged femoral scales. Both new species are distinguished from other congeners by a combination of the following characters: small subcaudal scales, not transversely enlarged; presence (C. phuocbinhensis sp. nov.) or absence (C. taynguyenensis sp. nov.) of enlarged femoral scales; number of preanal pores; and dorsal pattern. Genetic distances between described species and new species were 16.5% and 2.0% in COI and RPL35, respectively, for C. phuocbinhensis sp. nov., and these distances were 18.8% and 2.2% for C. taynguyenensis sp. nov., respectively. PMID- 25112762 TI - A new species of Leptolalax (Anura: Megophryidae) from the highest mountain in Indochina. AB - We describe a new species of Leptolalax from northern Vietnam. Leptolalax botsfordi sp. nov. is distinguished from its congeners by a combination of (1) supra-axillary and ventrolateral glands present; (2) dark brownish red ventral surface with white speckling; (3) medium body size for the genus (29.1-32.6 mm in 7 adult males, 30.0-31.8 mm in 2 females); (4) black markings on the flanks absent; (5) toes with rudimentary webbing and weak lateral fringing; (6) large pectoral glands (1.1-1.9 mm; 4-6% SVL) and femoral glands (2.4-4.3 mm; 7-14% SVL); and (7) an advertisement call with a dominant frequency of 2.6-3.2 kHz (at 14.0o C). At present, the new species is known only from upper montane forest between 2,795-2,815 m elevation on Mount Fansipan, Hoang Lien National Park. To our knowledge, Leptolalax botsfordi sp. nov. occurs at higher elevations than any other species in the genus. If L. botsfordi sp. nov. is truly restricted to a narrow, high-elevation band, it is likely to be particularly vulnerable to the effects of climate change. The new species also faces the immediate threat of habitat degradation and pollution due to tourist activity. PMID- 25112764 TI - Ogleus pilarae, a new genus and species of leptocheliid tanaidacean (Crustacea: Peracarida: Tanaidomorpha) from the tropical Northwest Atlantic with observations on the genus Pseudonototanais Lang, 1973. AB - Ogleus pilarae n. gen., n. sp. (Leptocheliidae) is described from specimens collected at a depth of 28 m off the eastern coast of Puerto Rico. Morphologically the new genus appears to have its closest affinities with the type species of Heterotanais and those of the two subgenera belonging to Pseudonototanais sensu Gutu. Ogleus is distinguished from these and other leptocheliids by a combination of characters including a male antennule having three unfused peduncular articles, five aesthetasc-bearing flagellar articles with the first being greatly reduced and bearing a single cluster of aesthetascs, the shape of the male cheliped, and uropods of both sexes having an elongate endopod with five articles or incipient articles, the distalmost being distinctly longer than the first. The genus Pseudonototanais is rediagnosed to contain P. werthi, P. modestus (female holotype), and with reservations P. bransfieldensis. The Pseudonototanais subgenus Makassaritanais is elevated to full generic rank to contain M. angustus and M. bamberi. The male originally attributed to P. (M.) modestus, does not appear to be a leptocheliid since it has a short uropodal endopod appearing to have just two articles. The taxonomic status of some of the other taxa previously assigned to Pseudonototanais sensu lato or that are superficially similar to it is discussed. Overall, based on the females, the genera Ogleus and Makassaritanais may be more closely allied with genus Leptochelia Dana, 1849 than to Pseudonototanais and Heterotanais. A key to the male leptocheliid taxa having truncated or superficially subchelate-appearing chelae is presented. PMID- 25112763 TI - Studies in Mexican Tettigoniidae: a new genus of Copiphorini and the first description of male Conocephalus (Aphauropus) leptopterus Rehn and Hebard and the female of Insara acutitegmina Fontana, Buzzetti, Marino-Perez & Garcia Garcia. AB - A new genus belonging to the katydid tribe Copiphorini (Tettigoniidae: Conocephalinae) is established, Brachycaulopsis gen. nov., collected from the state of Chiapas, Mexico. Also provided are first descriptions for both the male of Conocephalus (Aphauropus) leptopterus Rehn & Hebard, 1915 (Conocephalinae: Conocephalini) and the female of Insara acutitegmina Fontana et al., 2011 (Phaneropterinae: Insarini). PMID- 25112765 TI - Redescription of Alatina alata (Reynaud, 1830) (Cnidaria: Cubozoa) from Bonaire, Dutch Caribbean. AB - Here we establish a neotype for Alatina alata (Reynaud, 1830) from the Dutch Caribbean island of Bonaire. The species was originally described one hundred and eighty three years ago as Carybdea alata in La Centurie Zoologique-a monograph published by Rene Primevere Lesson during the age of worldwide scientific exploration. While monitoring monthly reproductive swarms of A. alata medusae in Bonaire, we documented the ecology and sexual reproduction of this cubozoan species. Examination of forty six A. alata specimens and additional archived multimedia material in the collections of the National Museum of Natural History, Washington, DC revealed that A. alata is found at depths ranging from surface waters to 675 m. Additional studies have reported it at depths of up to 1607 m in the tropical and subtropical Atlantic Ocean. Herein, we resolve the taxonomic confusion long associated with A. alata due to a lack of detail in the original description and conflicting statements in the scientific literature. A new cubozoan character, the velarial lappet, is described for this taxon. The complete description provided here serves to stabilize the taxonomy of the second oldest box jellyfish species, and provide a thorough redescription of the species. PMID- 25112766 TI - A new species of Charinus Simon, 1892 from northeastern Brazil with comments on the potential distribution of the genus in Central and South Americas (Arachnida: Amblypygi: Charinidae). AB - A new species of the genus Charinus Simon, 1892 is described from caves in the Rio Grande do Norte, Brazil. This is the first record of the genus for the state. This paper presents a map of the Charinus species distribution in Brazil with new records and a map of potential distribution of the genus in South and Central Americas. An updated key for Charinus species from Brazil is also presented. PMID- 25112767 TI - Aglaopheniid hydroids (Cnidaria: Hydrozoa: Aglaopheniidae) from bathyal waters of the Flemish Cap, Flemish Pass, and Grand Banks of Newfoundland (NW Atlantic) . AB - Five species of aglaopheniid hydroids (Aglaophenopsis cornuta, Cladocarpus diana, C. formosus, C. integer, and Nematocarpus ramuliferus) were collected from the Flemish Cap, Flemish Pass, and Grand Banks of Newfoundland during surveys with bottom trawls, rock dredges, and scallop gear. All are infrequently reported species, with C. diana being discovered for the first time since its original description from Iceland. We document here the southernmost collections of C. diana and N. ramuliferus, both previously unknown in the western Atlantic. Each of the five species is described and illustrated based on fertile material, a key is provided for their identification, and bathymetric distributions are noted. Known depth ranges are extended for A. cornuta, C. diana, and C. integer. Aglaophenopsis and Nematocarpus are recognized as genera distinct from the polyphyletic Cladocarpus, based on the unique structure of the phylactocarp in the former, and the existence of appendages with nematothecae (ramuli) on almost all thecate internodes of hydrocladia in the latter. These appendages occur even in the absence of gonothecae, and are here considered defensive structures that protect the hydranths. In differing from typical phylactocarps, we accept the contention that they are characters of generic value. PMID- 25112768 TI - A new solifugae species of Mummucina Roewer, 1934 (Solifugae, Mummuciidae) from the Northwest of Argentina. AB - A new species of Mummuciidae, Mummucina puna sp. nov. (male and female) from Northwest Puna eco-region of Salta province, Argentina, is described and illustrated. A key and distribution map of known species of the genus Mummucina are provided. PMID- 25112769 TI - Four new troglobiotic species of the genus Megalothorax Willem, 1900 (Collembola: Neelipleona) from the Carpathian Mountains (Slovakia, Romania). AB - Four new species of Megalothorax Willem, 1900 are described and illustrated: M. tatrensis sp. nov., M. carpaticus sp. nov., M. hipmani sp. nov. from caves in Slovakia and M. draco sp. nov. from the Dracoaia Cave in western Romania. The species represent troglobiotic forms exhibiting different level of troglomorphy involving such features as larger body, elongated foot complex, antennae, mucro and body chaetae. The most pronounced troglomorphy is observed in M. hipmani sp. nov. and M. draco sp. nov. Species descriptions are completed with comparative tables of chaetotaxy of antennae and legs. Diagnostic table for all congeners and dichotomous identification key to the world species are provided. Distribution records of other Megalothorax species in Slovakia are added. PMID- 25112770 TI - New species of Floresorchestia from Micronesia living in unusual habitats (Crustacea, Amphipoda, Talitridae). AB - The first freshwater talitrid, Floresorchestia pohnpei sp. nov., is described from the island of Pohnpei, Micronesia. Floresorchestia palau sp. nov. is described from supralittoral and shallow-water marine habitats in Palau, Micronesia. PMID- 25112771 TI - Neoliomera moana, a new cavernicolous species of xanthid crab from the Marquesas Islands (Crustacea: Decapoda: Brachyura). AB - A new crab Liomerinae, Neoliomera moana sp. nov., is described from the Marquesas Islands, based on three specimens collected by hand at the entrance of submarine caves at depths of 6-28 m. Within the genus the new species belongs to a group of six species that have the carapace cristate on the anterolateral margins. It can be recognized by the presence of a double crest on the upper margin of the palm of chela and by its colour pattern, with about twenty red spots on the dorsal surface of the carapace. This new species is considered has a potential endemic form to the Marquesas Islands. PMID- 25112772 TI - Neostylidium, a new generic replacement name for Stylidium Dall 1907 (Gastropoda: Caenogastropoda: Cerithiidae) non Eichwald 1855 (Anthozoa). PMID- 25112773 TI - The genus Asuridia Hampson, 1900 in Taiwan, with descriptions of two new species (Erebidae, Arctiinae, Lithosiini). PMID- 25112775 TI - Circulating hematopoietic progenitor cells in essential thrombocythemia versus prefibrotic/early primary myelofibrosis. PMID- 25112776 TI - Enhanced separation of potassium ions by spontaneous K+-induced self-assembly of a novel metal-organic framework and excess specific cation-pi interactions. AB - A novel metal-organic framework (MOF) was fabricated by spontaneous K(+)-induced supramolecular self-assembly with the embedded tripodal ligand units. When the 3D ligand was loaded onto Fe3O4@mSiO2 core-shell nanoparticles, it could effectively separate K(+) ions from a mixture of Na(+), K(+), Mg(2+), and Ca(2+) ions through nanoparticle-assisted MOF crystallization into a Fe3O4@mSiO2@MOF hybrid material. Excess potassium ions could be extracted because of the specific cation-pi interaction between K(+) and the aromatic cavity of the MOF, leading to enhanced separation efficiency and suggesting a new application for MOFs. PMID- 25112778 TI - MRI dedicated to bones and joints: what are their market shares in terms of number of patients in private practice in France? AB - PURPOSE: The French government plans to install MRI facilities dedicated to musculoskeletal indications. We have analyzed the use of imaging investigations in the community to assess their market share. MATERIALS AND METHODS: We undertook a retrospective analysis of all reimbursements during the year 2012 by the French Social Plan for Independent Workers for 4 imaging methods for a musculoskeletal indication (MRI, CT scan with or without opacification and contrast-enhanced conventional radiography). RESULTS: Three hundred and thirty two thousand eight hundred and ninety-three beneficiaries were included. The following investigations were used: MRI 12659 investigations; CT scan without direct opacification 7392; CT scan with direct opacification 1271; contrast enhanced conventional radiography 1187. Of those beneficiaries who underwent investigations of the spine, 39.91% had MRI alone, 8.62% had both MRI and one of the other investigations and 51.46% did not have MRI. The corresponding figures for beneficiaries undergoing lower limb investigations were 79.57%, 4.53% and 15.90% and those for beneficiaries undergoing upper limb investigations were 35.49%, 6.56% and 57.94% respectively. CONCLUSION: In terms of the numbers of investigations, our results show that in France MRI dedicated to musculoskeletal indications has a wide market share for the spine, upper and lower limbs. PMID- 25112777 TI - Increased Platelet Distribution Width Is Associated With Severity of Coronary Artery Disease in Patients With Acute Coronary Syndrome. AB - Platelet activation plays a pivotal role in acute coronary syndrome (ACS). We investigated the relationship between platelet distribution width (PDW) and severity of coronary artery disease (CAD) in patients with ACS. A total of 502 patients with ACS were enrolled. High (n = 151) and low PDW (n = 351) groups were defined as patients having values in the third tertile (>17%) and lower 2 tertiles (<=17%). There were significantly higher Gensini score (44 [10-168] vs. 36 [2-132], P < .001), and neutrophil-lymphocyte ratio (3.1 [0.8-12.4] vs. .2.5 [0.3-13], P = .012) and baseline platelet counts were significantly lower (220 [61-623] vs. 233 [79-644] 10(3)/mm3, P = .022) in the high PDW group. The variables PDW >17%, diabetes mellitus, and myocardial infarction were found to be associated with high Gensini score (odds ratio [OR]: 1.91, 95% confidence interval [CI]: 1.27-2.88, P = .002; OR: 2.85, 95% CI: 1.91-4.25, P < .001; OR: 2.67, 95% CI:1.74-4.1, P < .001, respectively). An increased PDW (>17%) is associated with severity of CAD in patients with ACS. PMID- 25112780 TI - High-density monolayers of metal complexes: preparation and catalysis. AB - Catalysts are one of the key materials for realizing a sustainable society. However, we may encounter problematic cases where conventional catalyst systems cannot provide effective solutions. We thus believe that the establishment of novel methods of catalyst preparation is currently necessary. Utilization of high density monolayers of molecular metal complexes is our strategy, and we expect that this methodology will enable facile and systematic screening of unique and efficient catalysts. This Personal Account describes our challenges to establish such an immature method in catalyst preparation as well as the related background and perspective. Preparation and catalysis by high-density monolayers of Rh complexes with N-heterocyclic carbene, structurally compact phosphine and diisocyanide ligands on gold surfaces are presented. The catalytic application of a high-density Pd-bisoxazoline complex prepared on a single-crystal silicon surface is also shown. Uniquely high catalyst turnover numbers and high chemoselectivities were observed with these catalyst systems. PMID- 25112779 TI - Influences of age, gender, and circadian rhythm on deceleration capacity in subjects without evident heart diseases. AB - BACKGROUND: Deceleration capacity (DC) is a newly found predictor of mortality after myocardial infarction. Age-, gender-, and circadian rhythm-related differences in DC may limit its predictive value, which should be considered in clinical settings. METHODS: DC, average heart rate, and HRV parameters, including 24 hours, awaking state (15:00-20:00) and sleeping mode (00:00-05:00) strips from 24 hours Holter recordings in 636 subjects without heart diseases were examined. Heart rate variability was analyzed in time domains (standard deviation of all normal-to-normal intervals [SDNN], normal-to-normal RR intervals in all 5-minute segments [SDANN], and root mean square successive difference [RMSSD]). RESULTS: The DC, SDNN, SDANN, RMSSD, and heart rate decreased with age. Deceleration capacity was significantly lower in patients greater than 50 years of age. The largest decrease of SDNN, SDANN, and RMSSD occurred in patients 30-39 years of age. The values of SDNN, SDANN, and DC of women were lower than that of men in the young and middle-aged groups, but age-related decrease of DC in men was greater than that in women. Heart rate of women was significantly higher than that of men in younger subjects, especially in a sleeping mode. There were higher values of DC and RMSSD during sleeping than that during a waking state. CONCLUSIONS: The age, gender, and circadian rhythm may be useful when evaluating cardiac autonomic function and need to be considered when evaluating DC and HRV in clinical and scientific researches. PMID- 25112782 TI - The acceptability and usefulness of mindfulness-based cognitive therapy for people living with psoriasis: a qualitative study. PMID- 25112781 TI - Impact of the expression of thymidylate synthase and dihydropyrimidine dehydrogenase genes on survival in stage II/III gastric cancer. AB - BACKGROUND: The efficacy of 5-fluorouracil (5FU)-based therapy, which remains the cornerstone of gastrointestinal cancer treatment, depends upon the expression of enzymes involved in pyrimidine metabolism, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT). We analyzed the expression of these genes in patients enrolled in the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) and their possible roles as biomarkers for treatment outcomes. METHODS: Formalin-fixed, paraffin-embedded specimens were available for 829 of a total of 1,059 (78.3 %) patients. TS, DPD, TP, and OPRT expression was measured by RT-PCR in manually microdissected tumor specimens and normalized to the reference gene, beta-actin. The expression level of each gene was categorized as low or high using cutoffs at the 33.3rd, 50th, or 66.7th percentiles. RESULTS: The hazard ratio (HR) for overall survival (OS) after S-1 treatment versus surgery alone was significantly lower in high (>66.7th percentile; HR = 0.370; 95 % CI 0.221-0.619) compared to low (<66.7th percentile; HR = 0.757; 95 % CI 0.563-1.018) TS expression groups (P = 0.015). Similarly, the HR for OS after S-1 therapy versus surgery alone was significantly lower in high (>33.3rd percentile; HR = 0.520, 95 % CI 0.376-0.720) compared to low (<33.3rd percentile; HR = 0.848, 95 % CI 0.563 1.276) DPD expression groups (P = 0.065). There was no interaction between TP or OPRT expression and OS. CONCLUSIONS: This large biomarker study showed that high TS and DPD gene expression in tumors was associated with enhanced benefit from postoperative adjuvant S-1 treatment in gastric cancer. There was no interaction between TP and OPRT expression and S-1 treatment. PMID- 25112784 TI - Neurocomputational account of memory and perception: Thresholded and graded signals in the hippocampus. AB - Recent evidence suggests that the hippocampus, a region critical for long-term memory, also supports certain forms of high-level visual perception. A seemingly paradoxical finding is that, unlike the thresholded hippocampal signals associated with memory, the hippocampus produces graded, strength-based signals in perception. This article tests a neurocomputational model of the hippocampus, based on the complementary learning systems framework, to determine if the same model can account for both memory and perception, and whether it produces the appropriate thresholded and strength-based signals in these two types of tasks. The simulations showed that the hippocampus, and most prominently the CA1 subfield, produced graded signals when required to discriminate between highly similar stimuli in a perception task, but generated thresholded patterns of activity in recognition memory. A threshold was observed in recognition memory because pattern completion occurred for only some trials and completely failed to occur for others; conversely, in perception, pattern completion always occurred because of the high degree of item similarity. These results offer a neurocomputational account of the distinct hippocampal signals associated with perception and memory, and are broadly consistent with proposals that CA1 functions as a comparator of expected versus perceived events. We conclude that the hippocampal computations required for high-level perceptual discrimination are congruous with current neurocomputational models that account for recognition memory, and fit neatly into a broader description of the role of the hippocampus for the processing of complex relational information. PMID- 25112783 TI - A randomised clinical trial to evaluate the effects of Plantago ovata husk in Parkinson patients: changes in levodopa pharmacokinetics and biochemical parameters. AB - BACKGROUND: Plantago ovata husk therapy could be used in patients with Parkinson disease to reduce the symptoms of gastrointestinal disorders, but it is important to know whether this compound modifies levodopa pharmacokinetics. The maintenance of constant plasma concentrations of levodopa abolishes the clinical fluctuations in parkinsonian patients. The aim of this randomised clinical trial was to establish the influence of the fiber Plantago ovata husk in the pharmacokinetics of levodopa when administered to Parkinson patients well controlled by their oral medication. METHODS: To evaluate the effects of this fiber on several biochemical parameters. 18 volunteers participated in the study and received alternatively two treatments (Plantago ovata husk or placebo) with their usual levodopa/carbidopa oral dose. On days 0 (initial situation), 14 and 35 of the study, blood samples were taken to assess levodopa pharmacokinetics and to determine biochemical parameters. RESULTS: Levodopa Cmax was very similar in the initial situation (603.2 ng/ml) and after placebo administration (612.0 ng/ml), being slightly lower (547.8 ng/ml) when Plantago ovata husk was given. AUC was very similar in the three groups: initial situation.- 62.87 MUg.min/ml, fiber treatment.- 64.47 MUg.min/ml and placebo treatment.- 65.10 MUg.min/ml. Fiber reduced significantly the number of peaks observed in the levodopa concentrations, maintaining concentrations more stable. No significant differences were found in total cholesterol, LDL-cholesterol and triglycerides with the administration of Plantago ovata husk. CONCLUSIONS: Plantago ovata husk administration caused a smoothing and homogenization of levodopa absorption, providing more stable concentrations and final higher levels, resulting in a great benefit for patients. TRIAL REGISTRATION: EudraCT2006-000491-33. PMID- 25112786 TI - Mating system and environmental variation drive patterns of adaptation in Boechera spatifolia (Brassicaceae). AB - Determining the relative contribution of population genetic processes to the distribution of natural variation is a major goal of evolutionary biology. Here, we take advantage of variation in mating system to test the hypothesis that local adaptation is constrained by asexual reproduction. We explored patterns of variation in ecological traits and genome-wide molecular markers in Boechera spatifolia (Brassicaceae), a species that contains both apomictic (asexual) and sexual individuals. Using a combination of quantitative genetics, neutral genetic (SSR) and genome-wide single nucleotide polymorphism, we assessed the hypothesis that asexual lineages should have reduced signatures of adaptation relative to sexual conspecifics. All three measures (traits, SSRs, SNPs) demonstrated that apomicts are genetically distinct from sexuals, regardless of population location. Additionally, phylogenetic clustering revealed that the apomictic group shared a single common ancestor. Across the landscape, sexual genome-wide SNP variation was strongly associated with latitude (r(2) > 0.9), indicating that sexual populations have differentiated across an environmental gradient. Furthermore, flowering time and growth rate, as assessed in a common garden, strongly covary with the elevation and latitude of the source population. Despite a wide geographic distribution that largely overlaps with sexual populations, there was little evidence for differentiation in molecular markers or quantitative characters among apomictic populations. Combined, these data indicated that, in contrast to asexual populations, sexual populations show evidence of local adaptation. PMID- 25112785 TI - Toxicity and quality of life after choline-PET/CT directed salvage lymph node dissection and adjuvant radiotherapy in nodal recurrent prostate cancer. AB - BACKGROUND: In a previous study we demonstrated that, based on 11C/18 F-choline positron emission tomography-computerized-tomography as a diagnostic tool, salvage lymph node dissection (LND) plus adjuvant radiotherapy (ART) is feasible for treatment of pelvic/retroperitoneal nodal recurrence of prostate cancer (PCa). However, the toxicity of this combined treatment strategy has not been systematically investigated before. The aim of the current study was to evaluate the acute and late toxicity and quality of life of ART after LND in pelvic/retroperitoneal nodal recurrent PCa. MATERIAL AND METHODS: 43 patients with nodal recurrent PCa were treated with 46 LND followed by ART (mean 49.6 Gy total dose) at the sites of nodal recurrence. Toxicity of ART was analysed by physically examination (31/43, 72.1%), by requesting 15 frequent items of adverse events from the Common-Terminology-Criteria for Adverse Events Version 4.0 catalogue and by review of medical records. QLQ-C30 (EORTC quality of life assessment) and PR25 (prostate cancer module) questionnaires were used to investigate quality of life. Toxicity was evaluated before starting of ART, during ART (acute toxicity), after ART (mean 2.3 months) and at end of follow up (mean 3.2 years after end of ART) reflecting late toxicity. RESULTS: 71.7% (33/46) of 46 ART were treatment of pelvic, 10.9% (5/46) of retroperitoneal only and 28.3% (13/46) of pelvic and retroperitoneal regions. Overall 52 symptoms representing toxicities were observed before ART, 107 during ART, 88 after end of ART and 52 at latest follow up. Leading toxicities during ART were diarrhoea (19%, 20/107), urinary incontinence (16%, 17/107) and fatigue (16%, 17/107). The spectrum of late toxicities was almost equal to those before beginning of ART. No grade 3 adverse events or chronic lymphedema at extremities were observed. We observed no clear correlation between localisation of treated regions, technique of ART and frequency or severity of toxicities. Mean quality of life at final evaluation was 74%. CONCLUSION: ART after extended LND in PCa relapse is justifiable with respect to adverse effects and toxicity. The side effects were circumscribed and well tolerated. The spectrum of adverse events at latest follow up was almost equal to those before start of ART. PMID- 25112787 TI - Pathophysiology of blast-induced ocular trauma in rats after repeated exposure to low-level blast overpressure. AB - BACKGROUND: The incidence of blast-induced ocular injury has dramatically increased due to advances in weaponry and military tactics. A single exposure to blast overpressure (BOP) has been shown to cause damage to the eye in animal models; however, on the battlefield, military personnel are exposed to BOP multiple times. The effects of repeated exposures to BOP on ocular tissues have not been investigated. The purpose of this study is to characterize the effects of single or repeated exposure on ocular tissues. METHODS: A compressed air shock tube was used to deliver 70 +/- 7 KPa BOP to rats, once (single blast overpressure [SBOP]) or once daily for 5 days (repeated blast overpressure [RBOP]). Immunohistochemistry was performed to characterize the pathophysiology of ocular injuries induced by SBOP and RBOP. Apoptosis was determined by quantification activated caspase 3. Gliosis was examined by detection of glial fibrillary acidic protein (GFAP). Inflammation was examined by detection of CD68. RESULTS: Activated caspase 3 was detected in ocular tissues from all animals subjected to BOP, while those exposed to RBOP had more activated caspase 3 in the optic nerve than those exposed to SBOP. GFAP was detected in the retinas from all animals subjected to BOP. CD68 was detected in optic nerves from all animals exposed to BOP. CONCLUSION: SBOP and RBOP induced retinal damage. RBOP caused more apoptosis in the optic nerve than SBOP, suggesting that RBOP causes more severe optic neuropathy than SBOP. SBOP and RBOP caused gliosis in the retina and increased inflammation in the optic nerve. PMID- 25112788 TI - Altered expression of transforming growth factor-beta isoforms in bovine cystic ovarian disease. AB - Cystic ovarian disease (COD) is one of the main causes of infertility in dairy cattle. It has been shown that intra-ovarian factors may contribute to follicular persistence. Transforming growth factor-beta (TGFB) isoforms are important paracrine and autocrine signalling molecules that regulate ovarian follicle growth and physiology. Considering the importance of these factors in the ovarian physiology, in this study, we examined the expression of TGFB isoforms (TGFB1, TGFB2 and TGFB3) in the ovary of healthy cows and animals with spontaneous and adrenocorticotrophic hormone (ACTH)-induced COD. In the oestrous-synchronized control group, the expression of TGFB1 in granulosa and theca cells was higher in spontaneous cysts than in atretic or tertiary follicles. When we compared TGFB2 expression in granulosa cells from atretic or tertiary follicles from the oestrous-synchronized control group with that in ACTH-induced or spontaneous follicular cysts, we found a higher expression in the latter. The expression of the TGFB isoforms studied was also altered during folliculogenesis in both the spontaneous and ACTH-induced COD groups. As it has been previously shown that TGFB influences steroidogenesis, ovarian follicular proliferation and apoptosis, an alteration in its expression may contribute to the pathogenesis of this disease. PMID- 25112790 TI - Left ventricular ejection fraction by real-time three-dimensional echocardiography : The Necker cube for the naive realism of two-dimensional methods. PMID- 25112789 TI - Effect of genetic and climatic variability on the metabolic profiles of black gram (Vigna mungo L.) seeds and sprouts. AB - BACKGROUND: Black gram is becoming increasingly of interest for consumers worldwide. The metabolomics have been conducted to reflect the life history of each individual plant. The metabolic pattern of black gram seeds and sprouts was profiled to investigate genetic and climatic influences on a broad range of chemical constituents. RESULTS: Distinct differences in metabolite profiles among three black gram varieties for both intact seeds and sprouts were observed. The differential impact of climate on metabolite profiles of the variety Chai Nat 80 during both dry and rainy seasons was investigated. Univariate statistical analysis demonstrated that greater maturity due to adequate moisture in the rainy season led to a higher content of nutritionally relevant polar metabolites, whereas the dry season resulted in a high relative amount of storage lipid because of immaturity due to insufficient rain and water supply. CONCLUSION: The investigation confirmed the potential of metabolite profiling to assist in breeding and farming practices. PMID- 25112791 TI - The relationship between self-injurious behavior and self-disclosure in adolescents with eating disorders. AB - PURPOSE: The aim of the current study is to examine the association between self disclosure and self-injurious behaviors among adolescent patients diagnosed with an eating disorder. METHODS: Sixty three female patients who fulfilled the DSM-IV diagnostic criteria of eating disorders were included (i.e. anorexia, bulimia, binge eating disorder and eating disorders not otherwise specified). Participants' age ranged from 11.5 to 20 years (M = 15.42, SD = 1.82). Participants completed self- report questionnaires about eating disorders, self disclosure, self-injurious behaviors (FASM) and depression (BDI-II) RESULTS: 82.5% of the sample endorsed severe self-injurious behaviors. A moderate negative relationship was found between general disclosure to parents and self-injurious behaviors indicating that patients who generally self-disclose to their parents (on different topics, apart from suicidal ideation) engage less frequently in self-injurious behaviors. In addition, the more patients self-disclose their suicidal ideation to others, the more they tend to self-injure. CONCLUSION: Self disclosure to parents on any topic may buffer against self-injurious behaviors and therefore it is important to work with adolescents suffering from eating disorders on effective self disclosure. In addition, self-disclosure about suicidal ideation to others by adolescents suffering from eating disorders should always be taken seriously, since it may be related to self-injurious behaviors. PMID- 25112792 TI - Suicidal behaviour and memory: A systematic review and meta-analysis. AB - OBJECTIVES: Suicidal behaviour results from a complex interplay between stressful events and vulnerability factors, including cognitive deficits. It is not yet clear if memory impairment is part of this specific vulnerability. Therefore, the objective of this study was to examine the association between memory deficits and vulnerability to suicidal acts. METHODS: A literature review was performed using Medline, Embase, and PsycInfo databases. Twenty-four studies (including 2,595 participants) met the selection criteria. Four different types of memory (i.e., working memory, short- and long-term memory, and autobiographical memory) were assessed in at least three different studies. RESULTS: Autobiographical memory was significantly less specific and more general in patients with a history of suicide attempt relative to those without such a history (Hedges' g = 0.8 and 0.9, respectively). Long-term memory and working memory were both more impaired in suicide attempters than in patient and healthy controls. Only short term memory did not differentiate suicide attempters from patient controls. CONCLUSIONS: Memory may play a significant role in the risk of suicidal acts, perhaps by preventing these individuals from using past experiences to solve current problems and to envision the future, and by altering inhibitory processes. More studies are necessary to better clarify these relationships. PMID- 25112793 TI - Controversy in mitral valve repair, resection or chordal replacement? AB - Mitral valve plasty has superseded valve replacement as the standard technique for treating degenerative mitral valve prolapse. Quadrangular resection is considered the gold standard for posterior leaflet prolapse. Chordal replacement was first developed to treat the anterior leaflet and subsequently became widely used for the posterior leaflet, after which a new version of posterior leaflet resection was developed that did not involve local annular plication. In the era of the mini-thoracotomy, the premeasured loop technique is simple to adopt and is as durable as quadrangular resection. However, there is controversy surrounding whether resection or chordal replacement is the optimal technique. The resection technique is curative because it removes the main pathologic lesion. The disadvantage of the resection is that it can be complicated and often requires advanced surgical skills. In contrast, chordal replacement is not pathologically curative because it leaves behind a redundant leaflet. However, the long-term results appear to be equivalent in many reports. Functionally, chordal replacement retains greater posterior leaflet motion with a lower trans-mitral pressure gradient than quadrangular resection. Moreover, chordal replacement is simple and yields uniform results. The optimal technique depends on whether the anterior leaflet or posterior leaflet is involved, the Barlow or non-Barlow disease state, and whether a mini-thoracotomy or standard sternotomy approach is used. For mitral valve repair, the most superior and reliable technique for the posterior leaflet is resection using the newer resection technique with a sternotomy approach, which requires a skilled surgeon. PMID- 25112794 TI - Richards-like two species population dynamics model. AB - The two-species population dynamics model is the simplest paradigm of inter- and intra-species interaction. Here, we present a generalized Lotka-Volterra model with intraspecific competition, which retrieves as particular cases, some well known models. The generalization parameter is related to the species habitat dimensionality and their interaction range. Contrary to standard models, the species coupling parameters are general, not restricted to non-negative values. Therefore, they may represent different ecological regimes, which are derived from the asymptotic solution stability analysis and are represented in a phase diagram. In this diagram, we have identified a forbidden region in the mutualism regime, and a survival/extinction transition with dependence on initial conditions for the competition regime. Also, we shed light on two types of predation and competition: weak, if there are species coexistence, or strong, if at least one species is extinguished. PMID- 25112796 TI - Motion analysis of the upper extremity in children with unilateral cerebral palsy -an assessment of six daily tasks. AB - Restrictions in range of motion of the upper extremity are common in patients with unilateral cerebral palsy (CP). The purpose of this study was to investigate movement deviations of the upper extremity in children with unilateral CP by means of 3D motion capture as well as by the use of easy to use scores and questionnaires (MACS, MRC, MAS, ABILHAND-Kids). 16 children with a spastic, unilateral CP were included and compared to a group of 17 typically developing adolescents (TD). The movement time and range of motion (ROM) of six uni- and bimanual daily tasks were compared and correlated with the scores and questionnaires. Movement times increased significantly with involvement according to MACS in all tasks. The restrictions in ROM were pronounced in the forearm. As a compensatory mechanism the children of the MACS 2 and 3 groups showed increased trunk movement. Furthermore, there was a positive correlation between the MACS and the ABILHAND-Kids Questionnaire. In contrast to previous studies, which reported a correlation between the restrictions in ROM and the MACS, this study showed no consistent correlation between the restrictions in ROM neither with the MACS nor with the ABILHAND-Kids. While the MACS and the ABILHAND-Kids function as a simple rating tool for clinical use, the detailed analysis of different daily tasks using 3-D-motion capture provides more detailed information about the movement deviations and spatiotemporal parameters. PMID- 25112795 TI - Patterns of change in nonverbal cognition in adolescents with Down syndrome. AB - This study was designed to examine longitudinal change in nonverbal cognitive abilities across adolescence for 20 males with Down syndrome (DS). We used hierarchical linear modeling to examine the rate of change in performance on the subtests of the Leiter-R Brief IQ across four annual time points and to determine the relation between maternal IQ and level and rate of change in performance. Results indicated no significant change in IQ (standard scores) with age in the sample, suggesting IQ stability during adolescence for individuals with DS, although several participants performed at floor level on the standard scores for the Leiter-R, limiting interpretation. Growth scores, however, provide a metric of absolute ability level, allow for the examination of change in Leiter-R performance in all participants, and minimize floor effects. Results from the analysis of growth scores indicated significant gain in absolute nonverbal cognitive ability levels (growth score values) over time for the adolescents with DS, although the growth varied by subdomain. Maternal IQ did not explain variability in cognitive performance or change in that performance over time in our sample of adolescents with DS. PMID- 25112797 TI - Effect of concentration on the formation of rose bengal triplet state on microcrystalline cellulose: a combined laser-induced optoacoustic spectroscopy, diffuse reflectance flash photolysis, and luminescence study. AB - Laser-induced optoacoustic spectroscopy (LIOAS), diffuse reflectance laser flash photolysis (DRLFP), and laser-induced luminescence (LIL) have been applied in conjunction to the determination of triplet state quantum yields of Rose Bengal (RB) supported on microcrystalline cellulose, a strongly light-scattering solid. Among the three used methods, the only one capable of providing absolute triplet quantum yields is LIOAS, but DRLFP and LIL aid in demonstrating that the LIOAS signal arises in fact from the triplet state and confirm the trend found with RB concentration. The coherence found for the three techniques demonstrates the usefulness of the approach. Observed triplet quantum yields are nearly constant within a limited concentration range, after which they decay strongly due to the generation of inactive dye aggregates or energy trapping centers. When quantum yields are divided by the fraction of absorbed light exciting the dye, the quotient falls off steadily with concentration, following the same trend as the observed fluorescence quantum yield. The conditions that maximize triplet formation are determined as a compromise between the rising light absorption and the decrease of quantum yield with RB concentration. PMID- 25112798 TI - NMR crystallography: Applications to inorganic materials. AB - Current developments of NMR crystallography as well as some recent applications to diamagnetic inorganic solids are presented. First, we illustrate how solid state NMR data can be used in combination with diffraction data for the determination of the periodic part of the crystal structures, from the space group selection, to the structure determination over the refinement and validation processes. As ss-NMR, contrary to diffraction (powder and single crystal), is not restricted to periodic boundary conditions, ss-NMR data can be used to further complete the structural description of materials, including studies of local order/disorder, etc. This illustrated through examples, which are shown and discussed in the second part of this review. PMID- 25112799 TI - Obesity is a determinant of arterial stiffness independent of traditional risk factors in Asians with young-onset type 2 diabetes. AB - OBJECTIVE: Type 2 diabetes (T2DM) among the young population has become a serious concern globally, presumably due to the rising trend of obesity. Compared to other forms of diabetes, young-onset T2DM experiences more cardiovascular events and other vascular complications although the underlying mechanisms remain largely unknown. Increased arterial stiffness is a hallmark of vasculopathy. We aim to study the clinical and metabolic determinants of arterial stiffness in a cohort of multi-ethnic Asians with young-onset T2DM. METHODS: 179 subjects with T2DM onset age below 30 years old were selected in this cross sectional study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV). RESULTS: PWV was correlated with age, duration of diabetes, systolic blood pressure, alanine aminotransferase, urinary albumin-to-creatinine ratio (ACR) and eGFR in bivariate correlation analysis. However, PWV was only significantly correlated with body mass index (BMI), waist circumference, urinary ACR and eGFR after adjustment for age. Overweight individuals with young-onset T2DM had significantly higher PWV levels compared to their lean counterparts (7.3 +/- 2.4 m/s vs 6.4 +/- 2.3 m/s, p = 0.072 and p < 0.0001 without and with adjustment for age, respectively). Multivariable regression models revealed that age, BMI, eGFR and usage of insulin were independently associated with PWV. These 4 variables explained 35.5% variance in PWV levels. CONCLUSION: Age, BMI, renal function and insulin usage are the main determinants of PWV levels in Asians with young-onset T2DM. Notably, obesity is a modifiable determinant of arterial stiffness independent of high blood pressure, dyslipidemia and hyperglycemia in this population. PMID- 25112800 TI - Hemoglobin, iron metabolism and angiographic coronary artery disease (The Ludwigshafen Risk and Cardiovascular Health Study). AB - BACKGROUND: Anemia has been shown to be a risk factor for coronary artery disease and mortality. The involvement of body iron stores in the development of CAD remains controversial. So far, studies that examined hemoglobin and parameters of iron metabolism simultaneously do not exist. METHODS AND RESULTS: Hemoglobin and iron status were determined in 1480 patients with stable angiographic coronary artery disease (CAD) and in 682 individuals in whom CAD had been ruled out by angiography. The multivariate adjusted odds ratios (OR) for CAD in the lowest quartiles of hemoglobin and iron were 1.62 (95%CI: 1.22-2.16), and 2.05 (95%CI: 1.51-2.78), respectively compared to their highest gender-specific quartiles. The fully adjusted ORs for CAD in the lowest quartiles of transferrin saturation, ferritin (F) and soluble transferrin receptor (sTfR)/log10F index were 1.69 (95%CI: 1.25-2.27), 1.98 (95%CI: 1.48-2.65), and 1.64 (95%CI: 1.23-2.18), respectively compared to their highest gender-specific quartiles. When adjusting in addition for iron and ferritin the OR for CAD in the lowest quartiles of hemoglobin was still 1.40 (95%CI: 1.04-1.90) compared to the highest gender specific quartiles. Thus, the associations between either iron status or low hemoglobin and CAD appeared independent from each other. The sTfR was only marginally associated with angiographic CAD. CONCLUSIONS: Both low hemoglobin and iron depletion are independently associated with angiographic CAD. PMID- 25112801 TI - Single nucleotide polymorphism of CYP3A5*3 contributes to clopidogrel resistance in coronary artery disease patients among Tamilian population. AB - Clopidogrel is an antiplatelet drug. It is used for the treatment as well as for the prophylaxis of coronary artery disease. Clopidogrel resistance is an emerging problem in clinical settings. The aim of the present study was to evaluate the effect of CYP3A5*3 genetic polymorphism on clopidogrel resistance. One hundred and forty-seven patients from outpatient Department of Cardiology on 75 mg/day of clopidogrel as maintenance dose were recruited from April 2010 to July 2011. All subjects gave written informed consent to participate in the study. DNA extraction was performed using phenol chloroform extraction procedure and genotyping by standard Taqman based RT-PCR method. Platelet aggregation was done at the end of 7th and 14th day by using chronolog lumi Aggregometer which is expressed as impedance in ohms. Impedance values of >5 ohms at the end of 6 min were considered as clopidogrel resistance. Subjects (N = 147) were analysed for CYP3A5*3 polymorphism, of which 49 (33%) were found to be clopidogrel resistant. Homomutants of CYP3A5*3 gene had 2.78 (0.97-7.98; p < 0.05) fold risk and heteromutants had 2.4 (0.93-6.46; p < 0.05) fold risk of developing clopidogrel resistance. Carriers of defective allele G of CYP3A5*3 had higher propensity to cause clopidogrel resistance with an odds ratio of 1.63. Variant alleles and genotypes of CYP3A5*3 polymorphism contributed significantly to clopidogrel resistance with a higher odds ratio. Thus, pharmacogenomics paves way for the emergence of stratified medicine in clopidogrel therapy and personalised pharmacotherapy in ischaemic heart disease. PMID- 25112802 TI - The true incidence of traumatic spinal cord injuries. PMID- 25112804 TI - [The new tools of microbiological diagnosis of tuberculosis]. AB - This review focuses on the role of new tools in the "modern" microbiological diagnosis of tuberculosis. Traditional techniques of microscopy and culture remain essential to diagnostic certainty, but some innovations replace daily the older techniques such as the identification of Mycobacterium tuberculosis complex by immunochromatography or mass spectrometry MALDI-TOF type from positive cultures, or susceptibility testing in liquid medium. New tools that use molecular techniques have become important. They all have in common to optimize the fight against tuberculosis by reducing diagnostic delay. They also allow rapid detection of drug resistance. However, the techniques of gene amplification directly from clinical samples are still less sensitive than culture. Bacteriological diagnosis of tuberculosis disease therefore still relies on the complementarities of different phenotypic and molecular techniques. PMID- 25112805 TI - [A rare cause of chondritis]. PMID- 25112803 TI - Sinus node dysfunction in catecholaminergic polymorphic ventricular tachycardia: risk factor and potential therapeutic target? AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited heart rhythm disorder characterized by the occurrence of potentially life threatening polymorphic ventricular tachyarrhythmias in conditions of physical or emotional stress. The underlying cause is a dysregulation in intracellular Ca handling due to mutations in the sarcoplasmic reticulum Ca release unit. Recent experimental work suggests that sinus bradycardia, which is sometimes observed in CPVT patients, may be another primary defect caused by CPVT mutations. Herein, we review the pathophysiology of CPVT and discuss the role of sinus node dysfunction as a modulator of arrhythmia risk and potential therapeutic target. PMID- 25112806 TI - Resistance to rocuronium of rat diaphragm as compared with limb muscles. AB - BACKGROUND: Skeletal muscles are composed of different muscle fiber types. We investigated the different potency to rocuronium among diaphragm (DIA), extensor digitorum longus (EDL), and soleus (SOL) in vitro as well as to investigate the differences of acetylcholine receptors (AChRs) among these three typical kinds of muscles. MATERIALS AND METHODS: The isolated left hemidiaphragm nerve-muscle preparations, the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations were established to evaluate the potency to rocuronium. Concentration-response curves were constructed and the values of IC50 were obtained. The density of AChRs at the end plate and the number of AChRs per unit fiber cross fiber area (CSA), AChR affinity for muscle relaxants were evaluated. RESULTS: The concentration-twitch tension curves of rocuronium were significantly different. The curves demonstrated a shift to the right of the DIA compared with the EDL and SOL (P < 0.01), whereas no significant difference was observed between EDL and SOL (P > 0.05). IC50 was significantly largest in DIA, second largest in SOL, and smallest in EDL (P < 0.05). The number of AChRs per unit fiber CSA was largest in DIA, second largest in EDL, and smallest in SOL (P < 0.01 or P < 0.05). The DIA showed the lowest affinity of the AChRs, whereas the SOL showed the highest affinity. CONCLUSIONS: The resistance to rocuronium of DIA compared with EDL and SOL was verified. The DIA was characterized by the largest number of AChRs per unit fiber CSA and the lowest affinity of the AChRs. Although compared with SOL, EDL was proved to have larger number of AChRs per unit fiber CSA and the lower affinity of the AChRs. These findings may be the mechanisms of different potency to rocuronium in DIA, EDL, and SOL. The results of the study could help to explain the relationship between different composition of muscle fibers and the potency to muscle relaxants. Extra caution should be taken in clinical practice when monitoring muscle relaxation in anesthetic management using different muscles. PMID- 25112807 TI - Comparison of virtual bronchoscopy to fiber-optic bronchoscopy for assessment of inhalation injury severity. AB - PURPOSE: Compare virtual bronchoscopy (VB) to fiberoptic bronchoscopy (FOB) for scoring smoke inhalation injury (SII). METHODS: Swine underwent computerized tomography (CT) with VB and FOB before (0) and 24 and 48 h after SII. VB and FOB images were scored by 5 providers off line. RESULTS: FOB and VB scores increased over time (p<0.001) with FOB scoring higher than VB at 0 (0.30+/-0.79 vs. 0.03+/ 0.17), 24 h (4.21+/-1.68 vs. 2.47+/-1.50), and 48h (4.55+/-1.83 vs. 1.94+/-1.29). FOB and VB showed association with PaO2-to-FiO2 ratios (PFR) with areas under receiver operating characteristic curves (ROC): for PFR<=300, VB 0.830, FOB 0.863; for PFR<=200, VB 0.794, FOB 0.825; for PFR<=100, VB 0.747, FOB 0.777 (all p<0.001). FOB showed 80.3% specificity, 77% sensitivity, 88.8% negative predictive value (NPV), and 62.3% positive-predictive value (PPV) for PFR<=300 and VB showed 67.2% specificity, 85.5% sensitivity, 91.3% NPV, and 53.4% PPV. CONCLUSIONS: VB provided similar injury severity scores to FOB, correlated with PFR, and reliably detected airway narrowing. VB performed during admission CT may be a useful screening tool specifically to demonstrate airway narrowing induced by SII. PMID- 25112808 TI - Identification of drug-resistant subpopulations in canine hemangiosarcoma. AB - Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive to conventional chemotherapy. Despite numerous attempts to advance treatment options and improve outcomes, drug resistance remains a hurdle to successful therapy. To address this problem, we used recently characterized progenitor cell populations derived from canine hemangiosarcoma cell lines and grown as non adherent spheres to identify potential drug resistance mechanisms as well as drug resistant cell populations. Cells from sphere-forming cultures displayed enhanced resistance to chemotherapy drugs, expansion of dye-excluding side populations and altered ATP-binding cassette (ABC) transporter expression. Invasion studies demonstrated variability between cell lines as well as between sphere and monolayer cell populations. Collectively, our results suggest that sphere cell populations contain distinct subpopulations of drug-resistant cells that utilize multiple mechanisms to evade cytotoxic drugs. Our approach represents a new tool for the study of drug resistance in hemangiosarcoma, which could alter approaches for treating this disease. PMID- 25112809 TI - The influence of physiological noise correction on test-retest reliability of resting-state functional connectivity. AB - The utility and success of resting-state functional connectivity MRI (rs-fcMRI) depend critically on the reliability of this technique and the extent to which it accurately reflects neuronal function. One challenge is that rs-fcMRI is influenced by various sources of noise, particularly cardiac- and respiratory related signal variations. The goal of the current study was to evaluate the impact of various physiological noise correction techniques, specifically those that use independent cardiac and respiration measures, on the test-retest reliability of rs-fcMRI. A group of 25 subjects were each scanned at three time points--two within the same imaging session and another 2-3 months later. Physiological noise corrections accounted for significant variance, particularly in blood vessels, sagittal sinus, cerebrospinal fluid, and gray matter. The fraction of variance explained by each of these corrections was highly similar within subjects between sessions, but variable between subjects. Physiological corrections generally reduced intrasubject (between-session) variability, but also significantly reduced intersubject variability, and thus reduced the test retest reliability of estimating individual differences in functional connectivity. However, based on known nonneuronal mechanisms by which cardiac pulsation and respiration can lead to MRI signal changes, and the observation that the physiological noise itself is highly stable within individuals, removal of this noise will likely increase the validity of measured connectivity differences. Furthermore, removal of these fluctuations will lead to better estimates of average or group maps of connectivity. It is therefore recommended that studies apply physiological noise corrections but also be mindful of potential correlations with measures of interest. PMID- 25112811 TI - 8-year follow-up of central giant cell lesion mimicking apical periodontitis. AB - INTRODUCTION: Lesions of nonendodontic origin may mimic apical periodontitis. Central giant cell lesions (CGCLs) are aggressive or nonaggressive benign idiopathic intraosseous lesions of the jaw. This report describes a case of a CGCL in the periapical region of teeth #21-#26 of a 17-year-old female who sought orthodontic care because of a change in the position of tooth #23. METHODS: Clinical examination revealed mild facial asymmetry caused by increased volume in the mental region and cortical bone expansion but no cortical disruption. A panoramic radiograph showed a well-defined radiolucent osteolytic lesion involving teeth #21-#26. The cortical bone was not affected, and there was no root resorption. Incisional biopsy was performed, and the diagnosis was a CGCL. The lesion was enucleated surgically. CGCLs should be included in the differential diagnosis of jaw lesions that mimic apical periodontitis. RESULTS: The patient subsequently underwent orthodontic treatment successfully. CONCLUSIONS: The 8-year clinical and radiographic follow-up confirmed lesion remission, no recurrence, and pulp vitality of all teeth. PMID- 25112810 TI - Behavior of nickel-titanium instruments manufactured with different thermal treatments. AB - INTRODUCTION: The purpose of this study was to investigate if nickel-titanium instruments with similar designs manufactured by different thermal treatments would exhibit significantly different in vitro behavior. METHODS: Thirty-six instruments each of ProTaper Universal (PTU F1; Dentsply Maillefer, Ballaigues, Switzerland), ProFile Vortex (PV; Dentsply Tulsa Dental Specialties, Tulsa, OK), Vortex Blue (VB, Dentsply Tulsa Dental Specialties), and TYPHOON Infinite Flex NiTi (TYP; Clinician's Choice Dental Products, New Milford, CT) (all size 25/.06) were evaluated. Bending resistance, torsion at failure, and dynamic torsional tests were performed with the instruments (n = 12). Analysis of variance and Tukey post hoc tests were applied. RESULTS: Flexibility was significantly higher for TYP compared with the other 3 groups (P < .0001). With respect to the maximum torque at failure, PV group showed the highest resistance to twisting (torsional strength) among the analyzed instruments followed by VB, TYP, and PTU. The TYP group exhibited greater angular deflection at failure compared with the other groups (P < .0001). The mean dynamic torque scores during simulated canal preparation were highest for TYP (3.01 +/- 0.71 Ncm) and lowest for PV (1.62 +/- 0.79 Ncm). However, no significant differences were observed comparing groups PTU with TYP and VB and VB with PV (P > .05). The highest mean forces were recorded with PTU (7.02 +/- 2.36 N) and the lowest with TYP (1.22 +/- 0.40 N). CONCLUSIONS: TYP instruments were significantly more flexible than the other instruments tested. The PV group had the highest torsional strength and TYP, despite being the most flexible, showed similar torsional moments to the other instruments, whereas its angular deflection was the highest among the groups. PMID- 25112813 TI - Nasotracheal intubation with airway scope. PMID- 25112812 TI - Predictors of hypofibrinogenemia in blunt trauma patients on admission. AB - PURPOSE: Massive bleeding usually leads to critically low levels of clotting factors, including fibrinogen. Although reduced fibrinogen levels correlate with increased mortality, predictors of hypofibrinogenemia have remained poorly understood. We investigated whether findings available on admission can be used as predictors of hypofibrinogenemia. METHODS: We retrospectively reviewed serum fibrinogen levels tested on arrival in 290 blunt trauma patients transported to a level I trauma center during a 3-year period. The primary outcome was prehospital predictors for hypofibrinogenemia. Covariates included age, sex, prehospital fluid therapy, prehospital anatomical and physiological scores, time from injury, base excess, and lactate on arrival. All variables with values of p < 0.10 in univariate analysis were included in a multivariate logistic regression model. The relationships between the variables and the 7-day mortality rate were evaluated in a Cox proportional hazards model. RESULTS: Patient's age [odds ratio (OR): 0.97, p < 0.001], Triage Revised Trauma Score (T-RTS) (OR: 0.81, p = 0.003), and prehospital fluid therapy (OR: 2.54, p = 0.01) were detected as independent predictors for hypofibrinogenemia in multivariate logistic regression analysis. Serum fibrinogen level [hazard ratio (HR): 0.99, p = 0.01] and T-RTS (HR: 0.77, p < 0.01) were associated with the 7-day mortality rate. CONCLUSION: T RTS is considered to play an important role in predicting hypofibrinogenemia and 7-day mortality in blunt trauma patients. PMID- 25112814 TI - Signaling networks in MS: a systems-based approach to developing new pharmacological therapies. AB - The pathogenesis of multiple sclerosis (MS) involves alterations to multiple pathways and processes, which represent a significant challenge for developing more-effective therapies. Systems biology approaches that study pathway dysregulation should offer benefits by integrating molecular networks and dynamic models with current biological knowledge for understanding disease heterogeneity and response to therapy. In MS, abnormalities have been identified in several cytokine-signaling pathways, as well as those of other immune receptors. Among the downstream molecules implicated are Jak/Stat, NF-Kb, ERK1/3, p38 or Jun/Fos. Together, these data suggest that MS is likely to be associated with abnormalities in apoptosis/cell death, microglia activation, blood-brain barrier functioning, immune responses, cytokine production, and/or oxidative stress, although which pathways contribute to the cascade of damage and can be modulated remains an open question. While current MS drugs target some of these pathways, others remain untouched. Here, we propose a pragmatic systems analysis approach that involves the large-scale extraction of processes and pathways relevant to MS. These data serve as a scaffold on which computational modeling can be performed to identify disease subgroups based on the contribution of different processes. Such an analysis, targeting these relevant MS-signaling pathways, offers the opportunity to accelerate the development of novel individual or combination therapies. PMID- 25112815 TI - 'It feels like someone is hammering my feet': understanding pain and its management from the perspective of people with multiple sclerosis. AB - BACKGROUND: Pain affects around 63% of people with multiple sclerosis (pwMS). Biomedical treatments demonstrate limited efficacy. More research is needed to understand pain from the individual's perspective in order to better inform a patient-centred approach that improves engagement, self-management and outcome. OBJECTIVE: The objective of this paper is to explore pwMS' experience and responses to pain, and their perspectives on pain management. METHODS: Twenty five in-depth, semi-structured telephone interviews were conducted. Interviews were audiotaped, transcribed and analysed using an inductive thematic analysis approach with elements of grounded theory. RESULTS: Key themes included vivid descriptions of pain and beliefs that pain is unpredictable, a sign of damage and may worsen. Anger was a common emotional response. Two dominant pain management themes emerged: one related to pain reduction and another to acceptance. Those focusing on pain reduction appeared to engage in cycles in which they struggled with symptoms and experienced continued distress. CONCLUSION: Findings identify pain-related beliefs, emotional reactions and disparate pain-management attitudes. All may influence pwMS' responses to pain and what they ask of their clinicians. Uncovering pwMS' personal beliefs about pain, and introducing a broader biopsychosocial understanding of pain in the clinical context, may provide opportunities to rectify potentially unhelpful management choices and enhance pain acceptance. PMID- 25112816 TI - Factors associated with clinically significant increased walking time in multiple sclerosis: results of a survival analysis of short-term follow-up data from a clinical database. AB - BACKGROUND: Because multiple sclerosis (MS) is variable and unpredictable, if symptom worsening could be predicted, patients may feel better prepared to manage changes in function. OBJECTIVE: The objective of this paper is to study the prediction of walking impairment in MS. METHODS: We retrieved data for all MS patients at our center (2008-2009), including baseline and follow-up timed 25 foot walk (T25FW) times. We assessed the incidence of >=20% worsening in T25FW by developing two survival models: (1) disease course and (2) Multiple Sclerosis Performance Scales (MSPS) score. The outcome was days until >=20% worsening in T25FW. Covariates were disease subtype, years since diagnosis, Patient Health Questionnaire-9 (PHQ-9) score, and demographics. Data were interval censored; missing data were handled with multiple imputation. RESULTS: Of 1544 patients, 309 (20%) experienced >=20% worsening T25FW. For disease course, time to worsening was significantly shorter for secondary progressive vs. relapsing remitting disease (p < 0.001). For MSPS, patients with lower baseline MSPS scores progressed more slowly (p = 0.001). In both models, sex, baseline T25W, and time since diagnosis were significantly associated with worsening. In the disease course model, PHQ 9 score may be related to worsening (p = 0.07). CONCLUSION: These findings suggest factors associated with worsening in T25FW and a potential approach to establishing indicators associated with clinically significant change. PMID- 25112817 TI - The effect of prolonged natalizumab treatment on anxiety and safety in JC virus seropositive MS patients; a follow-up study. PMID- 25112818 TI - Poor self-recognition of disordered eating among girls with bulimic-type eating disorders: cause for concern? AB - AIM: Bulimic-type eating disorders are common among young women and associated with high levels of distress and disability and low uptake of mental health care. We examined self-recognition of disordered eating and factors associated with this among female adolescents with bulimic-type eating disorders (n = 139) recruited from a large, population-based sample. METHODS: A vignette of a fictional character with bulimia nervosa was presented, followed by a series of questions addressing the nature and treatment of the problem described. One of these questions required participants to indicate whether they currently had a problem such as the one described. Self-report measures of eating disorder symptoms, general psychological distress and quality of life were also completed. RESULTS: More than half of participants (58%) did not believe that they currently had a problem with their eating. In multivariable analysis, impairment in emotional well-being and self-induced vomiting were the only variables independently associated with self-recognition. Participants who recognized a problem with their eating were more likely to have sought treatment for an eating problem than those who did not. CONCLUSIONS: Recognition of disordered eating among adolescents with bulimic-type eating disorders may be poor and this may be a factor in low uptake of mental health care. Health promotion efforts may need to address the misconception that only bulimic-type disorders involving self induced vomiting are pathological. PMID- 25112819 TI - Application of water footprint combined with a unified virtual crop pattern to evaluate crop water productivity in grain production in China. AB - Water shortages are detrimental to China's grain production while food production consumes a great deal of water causing water crises and ecological impacts. Increasing crop water productivity (CWP) is critical, so China is devoting significant resources to develop water-saving agricultural systems based on crop planning and agricultural water conservation planning. A comprehensive CWP index is necessary for such planning. Existing indices such as water use efficiency (WUE) and irrigation efficiency (IE) have limitations and are not suitable for the comprehensive evaluation of CWP. The water footprint (WF) index, calculated using effective precipitation and local water use, has advantages for CWP evaluation. Due to regional differences in crop patterns making the CWP difficult to compare directly across different regions, a unified virtual crop pattern is needed to calculate the WF. This project calculated and compared the WF of each grain crop and the integrated WFs of grain products with actual and virtual crop patterns in different regions of China for 2010. The results showed that there were significant differences for the WF among different crops in the same area or among different areas for the same crop. Rice had the highest WF at 1.39 m(3)/kg, while corn had the lowest at 0.91 m(3)/kg among the main grain crops. The WF of grain products was 1.25 m(3)/kg in China. Crop patterns had an important impact on WF of grain products because significant differences in WF were found between actual and virtual crop patterns in each region. The CWP level can be determined based on the WF of a virtual crop pattern, thereby helping optimize spatial distribution of crops and develop agricultural water savings to increase CWP. PMID- 25112820 TI - Asthma and asthma related symptoms in 23,326 Chinese children in relation to indoor and outdoor environmental factors: the Seven Northeastern Cities (SNEC) Study. AB - BACKGROUND: Both the levels and patterns of outdoor and indoor air pollutants have changed dramatically during the last decade in China. However, few studies have evaluated the effects of the present air pollution on the health of Chinese children. This study examines the association between outdoor and indoor air pollution and respiratory diseases among children living in Liaoning, a heavy industrial province of China. METHODS: A cross-sectional study of 23,326 Chinese children aged 6 to 13 years was conducted in 25 districts of 7 cities in Northeast China during 2009. Three-year (2006-2008) average concentrations of particles with an aerodynamic diameter of <=10 MUm (PM10), sulfur dioxide (SO2), nitrogen dioxides (NO2), and ozone (O3) were calculated from monitoring stations in each of the 25 districts. We used two-level logistic regression models to examine the effects of yearly variations in exposure to each pollutant, controlling for important covariates. RESULTS: The prevalence of respiratory symptoms was higher for those dwelling close to a busy road, those living near smokestacks or factories, those living with smokers, those living in one-story houses typically with small yards, and those with home renovation, bedroom carpet or pets. Ventilation device use was associated with decreased odds of asthma in children. The adjusted odds ratio for diagnosed-asthma was 1.34 (95% confidence interval [CI], 1.24-1.45) per 31 MUg/m(3) increase in PM10, 1.23 (95%CI, 1.14 1.32) per 21 MUg/m(3) increase in SO2, 1.25 (95%CI, 1.16-1.36) per 10 MUg/m(3) increase in NO2, and 1.31 (95%CI, 1.21-1.41) per 23 MUg/m(3) increase in O3, respectively. CONCLUSION: Outdoor and indoor air pollution was associated with an increased likelihood of respiratory morbidity among Chinese children. PMID- 25112821 TI - Trace metal partitioning over a tidal cycle in an estuary affected by acid mine drainage (Tinto estuary, SW Spain). AB - The Tinto River estuary is highly polluted with the acid lixiviates from old sulphide mines. In this work the behaviour of dissolved and particulate trace metals under strong chemical gradients during a tidal cycle is studied. The pH values range from 4.4 with low tide to 6.9 with high tide. Precipitation of Fe and Al is intense during rising tides and As and Pb are almost exclusively found in the particulate matter (PM). Sorption processes are very important in controlling the mobility (and hence bioavailability) of some metals and particularly affect Cu below pH 6. Above pH~6 Cu is desorbed, probably by the formation of Cu(I)-chloride complexes. Although less pronounced than Cu, also Zn desorption above pH 6.5 seems to occur. Mn and Co are affected by sorption processes at pH higher than ca. 6. Cd behaves conservatively and Ni is slightly affected by sorption processes. PMID- 25112822 TI - Short-term bioavailability of carbon in soil organic matter fractions of different particle sizes and densities in grassland ecosystems. AB - The quality, stability and availability of organic carbon (OC) in soil organic matter (SOM) can vary widely between differently managed ecosystems. Several approaches have been developed for isolating SOM fractions to examine their ecological roles, but links between the bioavailability of the OC of size-density fractions and soil microbial communities have not been previously explored. Thus, in the presented laboratory study we investigated the potential bioavailability of OC and the structure of associated microbial communities in different particle size and density fractions of SOM. For this we used samples from four grassland ecosystems with contrasting management intensity regimes and two soil types: a Haplic Cambisol and a typical Chernozem. A combined size-density fractionation protocol was applied to separate clay-associated SOM fractions (CF1, <1 MUm; CF2, 1-2 MUm) from light SOM fractions (LF1, <1.8 g cm(-3); LF2, 1.8-2.0 g cm(-3)). These fractions were used as carbon sources in a respiration experiment to determine their potential bioavailability. Measured CO2-release was used as an index of substrate accessibility and linked to the soil microbial community structure, as determined by phospholipid fatty acids (PLFA) analysis. Several key factors controlling decomposition processes, and thus the potential bioavailability of OC, were identified: management intensity and the plant community composition of the grasslands (both of which affect the chemical composition and turnover of OC) and specific properties of individual SOM fractions. The PLFA patterns highlighted differences in the composition of microbial communities associated with the examined grasslands, and SOM fractions, providing the first broad insights into their active microbial communities. From observed interactions between abiotic and biotic factors affecting the decomposition of SOM fractions we demonstrate that increasing management intensity could enhance the potential bioavailability of OC, not only in the active and intermediate SOM pools, but also in the passive pool. PMID- 25112823 TI - Effects of olive oil wastes on river basins and an oligotrophic coastal marine ecosystem: a case study in Greece. AB - This work aims to contribute to the knowledge of the impacts of olive oil waste discharge to freshwater and oligotrophic marine environments, since the ecological impact of olive oil wastes in riverine and coastal marine ecosystems, which are the final repositories of the pollutants, is a great environmental problem on a global scale, mostly concerning all the Mediterranean countries with olive oil production. Messinia, in southwestern Greece, is one of the greatest olive oil production areas in Europe. During the last decade around 1.4*10(6)tons of olive oil mill wastewater has been disposed in the rivers of Messinia and finally entered the marine ecosystem of Messiniakos gulf. The pollution from olive oil mill wastewater in the main rivers of Messinia and the oligotrophic coastal zone of Messiniakos gulf and its effects on marine organisms were evaluated, before, during and after the olive oil production period. Elevated amounts of phenols (36.2-178 mg L(-1)) and high concentrations of ammonium (7.29 18.9 mmol L(-1)) and inorganic phosphorus (0.5-7.48 mmol L(-1)) were measured in small streams where the liquid disposals from several olive oil industries were gathered before their discharge in the major rivers of Messinia. The large number of olive oil units has downgraded the riverine and marine ecosystems during the productive period and a period more than five months is needed for the recovery of the ecosystem. Statistical analysis showed that the enrichment of freshwater and the coastal zone of Messiniakos gulf in ammonia, nitrite, phenols, total organic carbon, copper, manganese and nickel was directly correlated with the wastes from olive oil. Toxicity tests using 24h LC50 Palaemonidae shrimp confirm that olive mill wastewater possesses very high toxicity in the aquatic environment. PMID- 25112824 TI - Serum regenerating islet-derived 3-alpha is a biomarker of mucosal enteropathies. AB - BACKGROUND: The clinical presentation of organic and functional intestinal disorders can overlap and clinicians often rely on invasive and time-consuming procedures to make a final diagnosis. Regenerating islet-derived 3-alpha (Reg3alpha) is detectable in the circulation of patients with intestinal graft versus host disease and patients with inflammatory bowel disease (IBD). AIM: To determine whether serum Reg3alpha testing is useful for discriminating mucosal enteropathies from functional intestinal disorders. METHODS: We prospectively included 47 patients with active coeliac disease (ACD), 13 patients with refractory coeliac disease (RCD), seven patients with common variable immunodeficiency (CVID), 72 patients with active Crohn's disease, 22 patients with active ulcerative colitis (UC) and 28 patients with irritable bowel syndrome (IBS)-related diarrhoea. Sera were also taken from 10 CD patients before and after 6-12 months of a gluten-free diet (GFD) and from 14 patients with IBD before and after induction therapy with Infliximab (IFX). Sera of 119 healthy volunteers were used to determine the cut-off value. Reg3alpha levels were measured by a commercial ELISA kit. RESULTS: Levels of Reg3alpha exceeded the cut off value of the assay in 43/47(91%) ACD patients, 13/13(100%) RCD patients, 7/7(100%) CVID patients, 65/72(90%) Crohn's disease patients, 17/22(77%) UC patients and one patient with IBS(4%). Reg3alpha levels distinguished mucosal enteropathies from IBS with a sensitivity of 90% and a specificity of 96%. Reg3alpha levels significantly decreased in CD patients following a GFD and in IBD patients after treatment with IFX. CONCLUSION: Reg3alpha is a serum biomarker of intestinal damage that, combined with clinical data, identifies patients who should undergo invasive tests for diagnosing enteropathies. PMID- 25112825 TI - Attending to the forest and the trees. Reply to comments on "Toward a computational framework for cognitive biology: unifying approaches from cognitive neuroscience and comparative cognition". PMID- 25112826 TI - Complex networks are not (so much) privileged: comment on "approaching human language with complex networks" by Cong and Liu. PMID- 25112827 TI - Fanconi syndrome and severe polyuria: an uncommon clinicobiological presentation of a Gitelman syndrome. AB - BACKGROUND: Gitelman syndrome is an autosomal recessive tubulopathy characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. The majority of patients do not present with symptoms until late childhood or adulthood, and the symptoms are generally mild. We report here the first case of Gitelman syndrome presenting with the biological features of Fanconi syndrome and an early polyuria since the neonatal period. We discuss in this article the atypical electrolytes losses found in our patient, as well as the possible mechanisms of severe polyuria. CASE PRESENTATION: A 6-year-old Caucasian girl was admitted via the Emergency department for vomiting, and initial laboratory investigations found hyponatremia, hypokalemia, metabolic acidosis with normal anion gap, hypophosphatemia, and hypouricemia. Urinalysis revealed Na, K, Ph and uric acid losses. Thus, the initial biological profile was in favor of a proximal tubular defect. However, etiological investigations were inconclusive and the patient was discharged with potassium chloride and phosphorus supplementation. Three weeks later, further laboratory analysis indicated persistent hypokalemia, a metabolic alkalosis, hypomagnesemia, and hypocalciuria. We therefore sequenced the SLC12A3 gene and found a compound heterozygosity for 2 known missense mutations. CONCLUSIONS: Gitelman syndrome can have varying and sometimes atypical presentations, and should be suspected in case of hypokalemic tubular disorders that do not belong to any obvious syndromic entity. In this case, the proximal tubular dysfunction could be secondary to the severe hypokalemia. This report emphasizes the need for clinicians to repeat laboratory tests in undiagnosed tubular disorders, especially not during decompensation episodes. PMID- 25112830 TI - TRAF6 is a nexus for TLR-STAT1 crosstalk. PMID- 25112829 TI - Protective genotypes in HIV infection reflect superior function of KIR3DS1+ over KIR3DL1+ CD8+ T cells. AB - Certain human class I histocompatibility-linked leukocyte antigen (HLA)/killer cell immunoglobulin-like receptor (KIR) genotypic combinations confer more favourable prognoses upon exposure to human immunodeficiency virus (HIV). These combinations influence natural killer (NK) cell function, thereby implicating NK cells in protection from HIV infection or disease progression. Because CD8(+) T cells restrict HIV replication, depend upon HLA class I antigen presentation and can also express KIR molecules, we investigated how these HLA/KIR combinations relate to the phenotype and function of CD8(+) T cells from uninfected controls and individuals with chronic HIV infection. CD8(+) T cells from KIR3DL1 and KIR3DS1 homozygous individuals, and expressing the corresponding KIR, were enumerated and phenotyped for CD127, CD57 and CD45RA expression. Ex vivo and in vitro responsiveness to antigen-specific and polyclonal stimulation was compared between KIR-expressing and non-expressing CD8(+) T cells by interferon-gamma production. There were higher numbers and fractions of KIR3DL1-expressing CD8(+) T cells in HIV-infected individuals independent of HLA-Bw4 co-expression, whereas expansion of KIR3DS1-expressing CD8(+) T cells reflected HLA-Bw4*80I co expression. KIR3DL1(+) and S1(+) CD8(+) T cells were predominantly CD127( )CD57(+)CD45RA(+). KIR3DL1-expressing CD8(+) T cells were insensitive to ex vivo stimulation with peptides from HIV or common viruses, but responded to anti-CD3 and recovered responsiveness to common viruses in vitro. Ex vivo non responsiveness of KIR3DL1-expressing CD8(+) T cells was also independent of HLA Bw4. KIR3DS1-expressing T cells responded normally to ex vivo antigenic stimulation, illustrating functional superiority over KIR3DL1(+) CD8(+) T cells. PMID- 25112832 TI - An innovative approach to providing collaborative education to undergraduate students in the area of child maltreatment. AB - Frontline workers in the area of child welfare often enter the field without having taken any specialized coursework in the area of child maltreatment. This article discusses an interdisciplinary certificate program that is specifically designed to teach persons from various academic areas the knowledge and skills necessary to work with children who experience maltreatment. The child advocacy studies certificate program specifically focuses on coursework in the area of child maltreatment and child advocacy to better train future frontline workers in their vital roles. This certificate will decrease underreporting of child abuse cases by mandated reporters by making them more aware of the signs and symptoms of child maltreatment and also give students a greater understanding of how to work with individuals from various fields. PMID- 25112831 TI - The pREset Stent Retriever for Endovascular Treatment of Stroke Caused by MCA Occlusion: Safety and Clinical Outcome. AB - PURPOSE: The purpose of this study was to analyze the safety and efficacy of the pREset device, a stent retriever system, for endovascular mechanical thrombectomy (MT) in acute ischemic stroke (AIS) after middle cerebral artery (MCA) occlusion. METHODS: Retrospectively, 48 consecutive patients (mean age +/- standard deviation, 71.0 +/- 11.9 years; 24 women) treated for acute MCA occlusion using pREset solely or in combination with other MT devices were identified. Recanalization success was evaluated using the modified thrombolysis in cerebral infarction score (TICI), and complications were detected by 24-h follow-up computed tomography or magnetic resonance imaging. MCA anatomy was assessed in angiograms. Clinical outcome was evaluated with National Institutes of Health Stroke Scale (NIHSS) score at admission and discharge, and modified Rankin scale (mRS) score at discharge and follow-up. RESULTS: Successful recanalization (TICI 2b/3) was achieved in 39 patients (81.3 %). Rate of procedure-related complications was 8.3 %. In four patients, a subarachnoid hemorrhage occurred (8.3 %), and parenchymal hematoma was detected in four patients (8.3 %). None of those events was associated with clinical deterioration. MCA curvature significantly influenced recanalization success (P < 0.005). Successful recanalization correlated significantly with lower NIHSS scores and favorable clinical outcome (mRS score 0-2) at discharge (P < 0.05). Mortality within 90 days was significantly lower in patients with TICI 2b/3 (P < 0.005). CONCLUSIONS: High recanalization rates, low complication rates, and a significantly improved outcome after successful recanalization strongly suggest that MT with pREset is an adequate therapy for AIS after MCA occlusion. Vessel curvature is a significant determining factor for recanalization success. PMID- 25112833 TI - Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet. AB - Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals, which is present ubiquitously in daily life. Accumulating evidence indicates that exposure to BPA contributes to metabolic syndrome. In this study, we examined whether perinatal exposure to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic syndrome. Wistar rats were exposed to 50 MUg/kg per day BPA or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a standard chow diet (SD) or a high-fat diet (HFD) after weaning. Effects of BPA were assessed by examination of hepatic morphology, biochemical analysis, and the hepatic expression of genes and/or proteins involved in lipogenesis, fatty acid oxidation, gluconeogenesis, insulin signaling, inflammation, and fibrosis. On a SD, the offspring of rats exposed to BPA exhibited moderate hepatic steatosis and altered expression of insulin signaling elements in the liver, but with normal liver function. On a HFD, the offspring of rats exposed to BPA showed a nonalcoholic steatohepatitis-like phenotype, characterized by extensive accumulation of lipids, large lipid droplets, profound ballooning degeneration, impaired liver function, increased inflammation, and even mild fibrosis in the liver. Perinatal exposure to BPA worsened the hepatic damage caused by the HFD in the rat offspring. The additive effects of BPA correlated with higher levels of hepatic oxidative stress. Collectively, exposure to BPA may be a new risk factor for the development of fatty liver disease and further studies should assess whether this finding is also relevant to the human population. PMID- 25112834 TI - Do patient-centered medical homes reduce emergency department visits? AB - OBJECTIVE: To assess whether adoption of the patient-centered medical home (PCMH) reduces emergency department (ED) utilization among patients with and without chronic illness. DATA SOURCES: Data from approximately 460,000 Independence Blue Cross patients enrolled in 280 primary care practices, all converting to PCMH status between 2008 and 2012. RESEARCH DESIGN: We estimate the effect of a practice becoming PCMH-certified on ED visits and costs using a difference-in differences approach which exploits variation in the timing of PCMH certification, employing either practice or patient fixed effects. We analyzed patients with and without chronic illness across six chronic illness categories. PRINCIPAL FINDINGS: Among chronically ill patients, transition to PCMH status was associated with 5-8 percent reductions in ED utilization. This finding was robust to a number of specifications, including analyzing avoidable and weekend ED visits alone. The largest reductions in ED visits are concentrated among chronic patients with diabetes and hypertension. CONCLUSIONS: Adoption of the PCMH model was associated with lower ED utilization for chronically ill patients, but not for those without chronic illness. The effectiveness of the PCMH model varies by chronic condition. Analysis of weekend and avoidable ED visits suggests that reductions in ED utilization stem from better management of chronic illness rather than expanding access to primary care clinics. PMID- 25112835 TI - Phylogenetic evidence for multiple intertypic recombinations in enterovirus B81 strains isolated in Tibet, China. AB - Enterovirus B81 (EV-B81) is a newly identified serotype within the species enterovirus B (EV-B). To date, only eight nucleotide sequences of EV-B81 have been published and only one full-length genome sequence (the prototype strain) has been made available in the GenBank database. Here, we report the full-length genome sequences of two EV-B81 strains isolated in the Tibet Autonomous Region of China during acute flaccid paralysis surveillance activities, and we also conducted an antibody seroprevalence study in two prefectures of Tibet. The sequence comparison and phylogenetic dendrogram analysis revealed high variability among the global EV-B81 strains and frequent intertypic recombination in the non-structural protein region of EV-B serotypes, suggesting high genetic diversity of EV-B81. However, low positive rates and low titers of neutralizing antibodies against EV-B81 were detected. Nearly 68% of children under the age of five had no neutralizing antibodies against EV-B81. Hence, the extent of transmission and the exposure of the population to this EV type are very limited. Although little is known about the biological and pathogenic properties of EV-B81 because of few research in this field owing to the limited number of isolates, our study provides basic information for further studies of EV-B81. PMID- 25112838 TI - Halobacterium rubrum sp. nov., isolated from a marine solar saltern. AB - Halophilic archaeal strain TGN-42-S1(T) was isolated from the Tanggu marine solar saltern, China. Cells from strain TGN-42-S1(T) were observed to be pleomorphic rods, stained Gram-negative, and formed red-pigmented colonies on solid media. Strain TGN-42-S1(T) was found to be able to grow at 20-50 degrees C (optimum 35 37 degrees C), at 1.7-4.8 M NaCl (optimum 3.1 M), at 0-1.0 M MgCl2 (optimum 0.1 M), and at pH 5.0-9.0 (optimum pH 7.0-7.5). The cells lysed in distilled water, and the minimal NaCl concentration to prevent cell-lysis was found to be 10 % (w/v). The major polar lipids of the strain were phosphatidic acid, phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate, galactosyl mannosyl glucosyl diether (TGD-1), sulfated galactosyl mannosyl glucosyl diether (S-TGD-1), sulfated galactosyl mannosyl galactofuranosyl glucosyl diether (S-TeGD), and three unidentified glycolipids which were chromatographically identical to those of the Halobacterium species. The 16S rRNA gene and rpoB' gene of strain TGN-42-S1(T) were phylogenetically related to the corresponding genes of Halobacterium jilantaiense CGMCC 1.5337(T) (98.8 and 93.5 % nucleotide identity, respectively), Halobacterium salinarum CGMCC 1.1958(T) (98.4 and 91.9 %), and Halobacterium noricense JCM 15102(T) (96.9 and 91.1 %). The DNA G + C content of strain TGN-42 S1(T) was determined to be 69.2 mol %. Strain TGN-42-S1(T) showed low DNA-DNA relatedness with Hbt. jilantaiense CGMCC 1.5337(T) and Hbt. salinarum CGMCC 1.1958(T), the most closely related members of the genus Halobacterium. The phenotypic, chemotaxonomic, and phylogenetic properties suggested that strain TGN 42-S1(T) (=CGMCC 1.12575(T) =JCM 19908(T)) represents a new species of Halobacterium, for which the name Halobacterium rubrum sp. nov. is proposed. PMID- 25112836 TI - Toll-like receptors in the pathogenesis of human B cell malignancies. AB - Toll-like receptors (TLRs) are important players in B-cell activation, maturation and memory and may be involved in the pathogenesis of B-cell lymphomas. Accumulating studies show differential expression in this heterogeneous group of cancers. Stimulation with TLR specific ligands, or agonists of their ligands, leads to aberrant responses in the malignant B-cells. According to current data, TLRs can be implicated in malignant transformation, tumor progression and immune evasion processes. Most of the studies focused on multiple myeloma and chronic lymphocytic leukemia, but in the last decade the putative role of TLRs in other types of B-cell lymphomas has gained much interest. The aim of this review is to discuss recent findings on the role of TLRs in normal B cell functioning and their role in the pathogenesis of B-cell malignancies. PMID- 25112839 TI - Basic fibroblastic growth factor affects the osteogenic differentiation of dental pulp stem cells in a treatment-dependent manner. AB - AIM: To determine how basic fibroblastic growth factor (bFGF) affected the osteogenic differentiation of human dental pulp stem cells (DPSCs) in vitro and in vivo. METHODOLOGY: Basic fibroblastic growth factor stimulation of DPSCs was divided into a pre-treatment period and an osteogenic differentiation period. Alizarin red quantification experiments and alkaline phosphatase activity quantification assay were performed to examine the osteogenic differentiation of DPSCs after different bFGF stimulation. Quantification reverse transcription polymerase chain reaction was used to analyze the osteogenic gene expression of DPSCs after different bFGF stimulation. In addition, DPSCs that received the 1 and 2 weeks bFGF pre-treatments as in the in vitro experiments were mineralized for 1 week and seeded into hydroxyapatite/tricalcium phosphate (HA/TCP) pills and subcutaneously transplanted into naked mice for 2 or 3 months. The transplants were removed, sliced and stained using Modified Ponceau Trichrome Stain to observe the formation of mineralized tissue. RESULTS: Basic fibroblastic growth factor stimulation in the osteogenic differentiation period decreased the in vitro osteogenic differentiation ability of DPSCs. One week pre-treatment with bFGF increased the in vitro osteogenic differentiation ability of DPSCs, whereas 2 weeks pre-treatment with bFGF decreased the in vitro osteogenic differentiation ability of DPSCs. The pre-treatment period was vital for the osteogenic differentiation of DPSCs in vitro. The in vivo results were similar to the in vitro results. CONCLUSIONS: Basic fibroblastic growth factor affected the osteogenic differentiation of DPSCs in a treatment-dependent manner both in vitro and in vivo. PMID- 25112840 TI - Generalized regression neural network (GRNN)-based approach for colored dissolved organic matter (CDOM) retrieval: case study of Connecticut River at Middle Haddam Station, USA. AB - The prediction of colored dissolved organic matter (CDOM) using artificial neural network approaches has received little attention in the past few decades. In this study, colored dissolved organic matter (CDOM) was modeled using generalized regression neural network (GRNN) and multiple linear regression (MLR) models as a function of Water temperature (TE), pH, specific conductance (SC), and turbidity (TU). Evaluation of the prediction accuracy of the models is based on the root mean square error (RMSE), mean absolute error (MAE), coefficient of correlation (CC), and Willmott's index of agreement (d). The results indicated that GRNN can be applied successfully for prediction of colored dissolved organic matter (CDOM). PMID- 25112841 TI - Potential effects of large linear pipeline construction on soil and vegetation in ecologically fragile regions. AB - Long-distance pipeline construction results in marked human disturbance of the regional ecosystem and brings into question the safety of pipeline construction with respect to the environment. Thus, the direct environmental impact and proper handling of such large projects have received much attention. The potential environmental effects, however, have not been fully addressed, particularly for large linear pipeline projects, and the threshold of such effects is unclear. In this study, two typical eco-fragile areas in western China, where large linear construction projects have been conducted, were chosen as the case study areas. Soil quality indices (SQI) and vegetation indices (VI), representing the most important potential effects, were used to analyze the scope of the effect of large pipeline construction on the surrounding environment. These two indices in different buffer zones along the pipeline were compared against the background values. The analysis resulted in three main findings. First, pipeline construction continues to influence the nearby eco-environment even after a 4 year recovery period. During this period, the effect on vegetation due to pipeline construction reaches 300 m beyond the working area, and is much larger in distance than the effect on soil, which is mainly confined to within 30 m either side of the pipeline, indicating that vegetation is more sensitive than soil to this type of human disturbance. However, the effect may not reach beyond 500 m from the pipeline. Second, the scope of the effect in terms of distance on vegetation may also be determined by the frequency of disturbance and the intensity of the pipeline construction. The greater the number of pipelines in an area, the higher the construction intensity and the more frequent the disturbance. Frequent disturbance may expand the effect on vegetation on both sides of the pipeline, but not on soil quality. Third, the construction may eliminate the stable, resident plant community. During the recovery period, the plant community in the work area of the pipeline is replaced by some species that are rare or uncommon in the resident plant community because of human disturbance, thereby increasing the plant diversity in the work area. In terms of plant succession, the duration of the recovery period has a direct effect on the composition and structure of the plant community. The findings provide a theoretical basis and scientific foundation for improving the environmental impact assessment (EIA) of oil and gas pipeline construction as it pertains to the desert steppe ecosystem, and provide a reference point for recovery and management of the eco-environment during the pipeline construction period. PMID- 25112842 TI - Biological response to physical processes in the Indian Ocean sector of the Southern Ocean: a case study in the coastal and oceanic waters. AB - The spatial variation of chlorophyll a (Chl a) and factors influencing the high Chl a were studied during austral summer based on the physical and biogeochemical parameters collected near the coastal waters of Antarctica in 2010 and a zonal section along 60 degrees S in 2011. In the coastal waters, high Chl a (>3 mg m( 3)) was observed near the upper layers (~15 m) between 53 degrees 30'E and 54 degrees 30'E. A comparatively higher mesozooplankton biomass (53.33 ml 100 m(-3)) was also observed concordant with the elevated Chl a. Low saline water formed by melting of glacial ice and snow, as well as deep mixed-layer depth (60 m) due to strong wind (>11 ms(-1)) could be the dominant factors for this biological response. In the open ocean, moderately high surface Chl a was observed (>0.6 mg m(-3)) between 47 degrees E and 50 degrees E along with a Deep Chlorophyll Maximum of ~1 mg m(-3) present at 30-40 m depth. Melt water advected from the Antarctic continent could be the prime reason for this high Chl a. The mesozooplankton biomass (22.76 ml 100 m(-3)) observed in the open ocean was comparatively lower than that in the coastal waters. Physical factors such as melting, advection of melt water from Antarctic continent, water masses and wind induced vertical mixing may be the possible reasons that led to the increase in phytoplankton biomass (Chl a). PMID- 25112843 TI - Two in one sweep: aluminum tolerance and grain yield in P-limited soils are associated to the same genomic region in West African sorghum. AB - BACKGROUND: Sorghum (Sorghum bicolor L. Moench) productivity is severely impeded by low phosphorus (P) and aluminum (Al) toxic soils in sub-Saharan Africa and especially West Africa (WA). Improving productivity of this staple crop under these harsh conditions is crucial to improve food security and farmer's incomes in WA. RESULTS: This is the first study to examine the genetics underlying sorghum adaptation to phosphorus limitation in a wide range of WA growing conditions. A set of 187 diverse sorghum genotypes were grown in 29 -P and + P field experiments from 2006-2012 in three WA countries. Sorghum grain yield performance under -P and + P conditions was highly correlated (r = 0.85***). Significant genotype-by-phosphorus interaction was detected but with small magnitude compared to the genotype variance component. We observed high genetic diversity within our panel, with rapid linkage disequilibrium decay, confirming recent sequence based studies in sorghum. Using genome wide association mapping based on 220 934 SNPs we identified one genomic region on chromosome 3 that was highly associated to grain yield production. A major Al-tolerance gene in sorghum, SbMATE, was collocated in this region and SbMATE specific SNPs showed very high associations to grain yield production, especially under -P conditions, explaining up to 16% of the genotypic variance. CONCLUSION: The results suggest that SbMATE has a possible pleiotropic role in providing tolerance to two of the most serious abiotic stresses for sorghum in WA, Al toxicity and P deficiency. The identified SNPs can help accelerate breeding for increased sorghum productivity under unfavorable soil conditions and contribute to assuring food security in WA. PMID- 25112845 TI - Effect of sulodexide in patients with non-proliferative diabetic retinopathy: diabetic retinopathy sulodexide study (DRESS). AB - PURPOSE: To evaluate the effectiveness of sulodexide for the treatment of hard exudates (HE) in non-proliferative diabetic retinopathy (NPDR). METHODS: This was a randomized, placebo-controlled, multicenter trial involving 130 patients (65 for each group) who had mild-to-moderate NPDR with macular HE. Participants were given a daily dose of either 50 mg sulodexide or a matching dose of placebo orally for 12 months. Main outcome measure was an improvement in HE defined as a decrease in severity by at least two grades on a 10-grade severity scale. This was evaluated by fundus photography over 12-month period. RESULTS: The sulodexide group showed significantly greater improvement in HE severity than that shown by the placebo group (39.0 % vs. 19.3 %; chi square, P = 0.005). Logistic regression analysis yielded an odds ratio of 2.790 (95 % confidence interval, 1.155-6.743; P = 0.023) for the effect of treatment once adjustments were made for demographic, prognostic and disease confounders. Intention to treat and per-protocol analysis yielded similar results. Sulodexide's safety was comparable to that of the placebo. CONCLUSIONS: Oral sulodexide therapy over 12 months improved macular HE in patients with mild-to-moderate NPDR, without leading to detectable adverse events. The study protocol was registered on clinicaltrial.gov under identifier NCT01295775. PMID- 25112848 TI - Pressure-driven ballistic Kelvin's water dropper for energy harvesting. AB - In this paper, we introduce a microfluidic-based self-excited energy conversion system inspired by Kelvin's water dropper but driven by inertia instead of gravity. Two micro water jets are produced by forcing water through two micropores by overpressure. The jets break up into microdroplets which are inductively charged by electrostatic gates. The droplets land on metal targets which are gradually charged up to high voltages. Targets and electrostatic gates are cross-connected in a way similar to Kelvin's water dropper. Application of pressure as driving force instead of gravity as in Kelvin's dropper allows for much higher energy densities. To prevent overcharging of the droplets by the inductive mechanism and consequent droplet loss by repulsion from the target as in Kelvin's water dropper, a voltage divider using inversely connected diodes was introduced in our system to control the charge induction providing self-limiting positive feedback by the diode characteristics. A maximal 18% energy conversion efficiency was obtained with the diode-gated system. PMID- 25112847 TI - Changes of TGF-beta2, MMP-2, and TIMP-2 levels in the vitreous of patients with high myopia. AB - PURPOSE: To investigate the concentrations of transforming growth factor (TGF) beta2, matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase (TIMP)-2 in the vitreous of patients with high myopia. METHODS: Twenty-six patients with high myopia (HM) who received vitrectomy for macular retinoschisis or macular hole were enrolled in this prospective study. Twenty-six patients with idiopathic macular hole or macular epiretinal membrane were chosen as a control group. Vitreous samples were obtained during the vitrectomy surgery. The levels of TGF-beta2,MMP-2,TIMP-2 in the vitreous samples were measured by enzyme-linked immunosorbent assay. The MMP activity was determined by a fluorometric assay. RESULTS: There was no significant difference in the vitreous level of TGF-beta2 between HM (1.64 +/- 0.38 ng/ml) and the control group (1.56 +/- 0.32 ng/ml, p = 0.56). The vitreous levels of MMP-2 in HM (32.40 +/- 14.90 ng/ml) were significantly higher than in the control group (21.42 +/- 6.74 ng/ml, p < 0.01). The ratio of MMP-2/TIMP-2 was significantly elevated in the vitreous samples from HM (0.61 +/- 0.19), compared to the control group (0.48 +/- 0.11, p < 0.05). The MMP activity was also significantly elevated in the vitreous samples from HM (4,030.8 +/- 1,257.3 FIU), compared to the control group (3,245.8 +/- 835.6 FIU, p < 0.05). CONCLUSIONS: The elevated MMP/TIMP ratio and MMP activity may play a role in the pathogenesis of human high myopia. Large prospective studies are needed to further investigate the effect of MMPs in the pathogenesis of human high myopia. PMID- 25112850 TI - Clinical trials: Placebo effects in interstitial cystitis/bladder pain syndrome. PMID- 25112846 TI - Investigation of blood flow regulation and oxygen saturation of the retinal vessels in primary open-angle glaucoma. AB - PURPOSE: To examine the supply of oxygen to the retina in primary open-angle glaucoma (POAG). METHODS: Forty-one patients with primary open-angle glaucoma (mean age 64.1 +/- 12.9 years) and 40 healthy subjects (63.6 +/- 14.1 years) were included. Fundus images, centered at the optic disc, were taken using the Retinal Vessel Analyzer (RVA). The vessel diameters were calculated as central retinal artery (CRAE) and vein equivalent (CRVE) from diameter measurements in the peripapillary vessels. The oxygen saturation of the arteries and veins was investigated employing a two-wavelengths technique. After the measurement at baseline, the vascular response to flicker light exposure was measured. RESULTS: In glaucoma patients the mean oxygen saturation of the retinal veins at baseline was higher than in the healthy controls (64.36 +/- 7.11 vs. 59.78 +/- 8.47, p = 0.01), whereas the mean arteriovenous oxygen saturation difference was lower (33.07 +/- 5.24 vs. 37.53 +/- 6.95, p = 0.002). The arterial oxygen saturation as well as the arterial and venous diameters showed no difference between the groups. The increase of the CRVE during flicker light stimulation (3.72 +/- 3.29 % vs. 5.43 +/- 4.04, p = 0.039), as well as the change of the venous oxygen saturation (2.08 +/- 3.74 % vs. 4.18 +/- 3.88 %, p = 0.016) and the arteriovenous saturation difference (-2.1 +/- 3.31 % vs. -4.43 +/- 3.6 %, p = 0.003) were smaller in POAG patients than in the healthy group. CONCLUSIONS: The reduction in the arteriovenous difference in oxygen saturation in POAG patients might show a decreased oxygen demand of the retina caused by the glaucomatous loss of neuroretinal tissue. The lower extent of the flicker light-induced change of the diameter of retinal veins and the venous oxygen saturation could indicate an impairment of blood flow regulation. PMID- 25112851 TI - Stones: Guidelines reignite interest in medical treatment of stones. PMID- 25112853 TI - Prostate cancer: Probing progression in circulating tumour cells. PMID- 25112854 TI - Beyond the G-spot: clitourethrovaginal complex anatomy in female orgasm. AB - The search for the legendary, highly erogenous vaginal region, the Grafenberg spot (G-spot), has produced important data, substantially improving understanding of the complex anatomy and physiology of sexual responses in women. Modern imaging techniques have enabled visualization of dynamic interactions of female genitals during self-sexual stimulation or coitus. Although no single structure consistent with a distinct G-spot has been identified, the vagina is not a passive organ but a highly dynamic structure with an active role in sexual arousal and intercourse. The anatomical relationships and dynamic interactions between the clitoris, urethra, and anterior vaginal wall have led to the concept of a clitourethrovaginal (CUV) complex, defining a variable, multifaceted morphofunctional area that, when properly stimulated during penetration, could induce orgasmic responses. Knowledge of the anatomy and physiology of the CUV complex might help to avoid damage to its neural, muscular, and vascular components during urological and gynaecological surgical procedures. PMID- 25112857 TI - Prostate cancer: Is active surveillance safe for obese patients? PMID- 25112858 TI - Surgery: Treating urotrauma--new guidelines to aid decisions. PMID- 25112860 TI - Sexual dysfunction: A practical approach to men with premature ejaculation. PMID- 25112861 TI - Prostate cancer: USPSTF screening recommendation could lead to greater numbers of avoidable deaths. PMID- 25112856 TI - Landmarks in the diagnosis and treatment of renal cell carcinoma. AB - The most common renal cancer is renal cell carcinoma (RCC), which arises from the renal parenchyma. The global incidence of RCC has increased over the past two decades by 2% per year. RCC is the most lethal of the common urological cancers: despite diagnostic advances, 20-30% of patients present with metastatic disease. A clearer understanding of the genetic basis of RCC has led to immune-based and targeted treatments for this chemoresistant cancer. Despite promising results in advanced disease, overall response rates and durable complete responses are rare. Surgery remains the main treatment modality, especially for organ-confined disease, with a selective role in advanced and metastatic disease. Smaller tumours are increasingly managed with biopsy, minimally invasive interventions and surveillance. The future promises multimodal, integrated and personalized care, with further understanding of the disease leading to new treatment options. PMID- 25112862 TI - Halotriazolium axle functionalised [2]rotaxanes for anion recognition: investigating the effects of halogen-bond donor and preorganisation. AB - The anion-templated synthesis of three novel halogen-bonding 5-halo-1,2,3 triazolium axle containing [2]rotaxanes is described, and the effects of altering the nature of the halogen-bond donor atom together with the degree of inter component preorganisation on the anion-recognition properties of the interlocked host investigated. The ability of the bromotriazolium motif to direct the halide anion-templated assembly of interpenetrated [2]pseudorotaxanes was studied initially; bromide was found to be the most effective template. As a consequence, bromide anion templation was used to synthesise the first bromotriazolium axle containing [2]rotaxane, the anion-binding properties of which, determined by (1) H NMR spectroscopic titration experiments, revealed enhanced bromide and iodide recognition relative to a hydrogen-bonding protic triazolium rotaxane analogue. Two halogen-bonding [2]rotaxanes with bromo- and iodotriazolium motifs integrated into shortened axles designed to increase inter-component preorganisation were also synthesised. Anion (1) H NMR spectroscopic titration experiments demonstrated that these rotaxanes were able to bind halide anions even more strongly, with the iodotriazolium axle integrated rotaxane capable of recognising halides in aqueous solvent media. Importantly, these observations suggest that a halogen-bonding interlocked host binding domain, in combination with increased inter-component preorganisation, are requisite design features for a potent anion receptor. PMID- 25112863 TI - Cause-specific mortality by race in low-income Black and White people with Type 2 diabetes. AB - AIM: To investigate, with extended follow-up, cause-specific mortality among low income Black and White Americans with Type 2 diabetes who have similar socio economic status. METHODS: Black and White Americans aged 40-79 years with Type 2 diabetes (n = 12 498) were recruited from community health centres as part of the Southern Community Cohort Study. Multivariable Cox analysis was used to estimate mortality hazard ratios and 95% CIs for subsequent cause-specific mortality, based on both underlying and contributing causes of death. RESULTS: During the follow-up (median 5.9 years), 13.3% of the study population died. The leading causes of death in each race were ischaemic heart disease, respiratory disorders, cancer, renal failure and heart failure; however, Blacks were at a lower risk of dying from ischaemic heart disease (hazard ratio 0.70, 95% CI 0.54-0.91) or respiratory disorders (hazard ratio 0.70, 0.53-0.92) than Whites but had higher or similar mortality attributable to renal failure (hazard ratio 1.57, 95% CI 1.02-2.40), heart failure (hazard ratio 1.47, 95% CI 0.98-2.19) and cancer (hazard ratio 0.87, 95% CI 0.62-1.22). Risk factors for each cause of death were generally similar in each race. CONCLUSIONS: These findings suggest that the leading causes of death and their risk factors are largely similar among Black and White Americans with diabetes. For the two leading causes of death in each race, however, ischaemic heart disease and respiratory disorders, the magnitude of risk is lower among Black Americans and contributes to their higher survival rates. PMID- 25112865 TI - Deferiprone in Friedreich ataxia: a 6-month randomized controlled trial. AB - OBJECTIVE: We conducted a 6-month, randomized, double-blind, placebo-controlled study to assess safety, tolerability, and efficacy of deferiprone in Friedreich ataxia (FRDA). METHODS: Seventy-two patients were treated with deferiprone 20, 40, or 60mg/kg/day or placebo, divided into 2 daily doses. Safety was the primary objective; secondary objectives included standardized neurological assessments (Friedreich Ataxia Rating Scale [FARS], International Cooperative Ataxia Rating Scale [ICARS], 9-Hole Peg Test [9HPT], Timed 25-Foot Walk, Low-Contrast Letter Acuity), general functional status (Activities of Daily Living), and cardiac assessments. RESULTS: Deferiprone was well tolerated at 20mg/kg/day, whereas more adverse events occurred in the 40mg/kg/day than in the placebo group. The 60mg/kg/day dose was discontinued due to worsening of ataxia in 2 patients. One patient on deferiprone 20mg/kg/day experienced reversible neutropenia, but none developed agranulocytosis. Deferiprone-treated patients receiving 20 or 40mg/kg/day showed a decline in the left ventricular mass index, compared to an increase in the placebo-treated patients. Patients receiving 20mg/kg/day of deferiprone had no significant change in FARS, similar to the placebo-treated patients, whereas those receiving 40mg/kg/day had worsening in FARS and ICARS scores. The lack of deterioration in the placebo arm impaired the ability to detect any potential protective effect of deferiprone. However, subgroup analyses in patients with less severe disease suggested a benefit of deferiprone 20mg/kg/day on ICARS, FARS, kinetic function, and 9HPT. INTERPRETATION: This study demonstrated an acceptable safety profile of deferiprone at 20mg/kg/day for the treatment of patients with FRDA. Subgroup analyses raise the possibility that, in patients with less severe disease, deferiprone 20mg/kg/day may reduce disease progression, whereas higher doses appear to worsen ataxia. PMID- 25112864 TI - Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice. AB - Alpha-synuclein (alpha-Syn) aggregates are the main component of Lewy bodies, which are the characteristic pathological feature in Parkinson's disease (PD) brain. Evidence that alpha-Syn aggregation can be propagated between neurones has led to the suggestion that this mechanism is responsible for the stepwise progression of PD pathology. Decreasing alpha-Syn expression is predicted to attenuate this process and is thus an attractive approach to delay or halt PD progression. We have used alpha-Syn small interfering RNA (siRNA) to reduce total and aggregated alpha-Syn levels in mouse brains. To achieve widespread delivery of siRNAs to the brain we have peripherally injected modified exosomes expressing Ravies virus glycoprotein loaded with siRNA. Normal mice were analyzed 3 or 7 days after injection. To evaluate whether this approach can decrease alpha-Syn aggregates, we repeated the treatment using transgenic mice expressing the human phosphorylation-mimic S129D alpha-Syn, which exhibits aggregation. In normal mice we detected significantly reduced alpha-Syn messenger RNA (mRNA) and protein levels throughout the brain 3 and 7 days after treatment with RVG-exosomes loaded with siRNA to alpha-Syn. In S129D alpha-Syn transgenic mice we found a decreased alpha-Syn mRNA and protein levels throughout the brain 7 days after injection. This resulted in significant reductions in intraneuronal protein aggregates, including in dopaminergic neurones of the substantia nigra. This study highlights the therapeutic potential of RVG-exosome delivery of siRNA to delay and reverse brain alpha-Syn pathological conditions. PMID- 25112867 TI - Evidence for a molecular diode-based mechanism in a multispecific ATP-binding cassette (ABC) exporter: SER-1368 as a gatekeeping residue in the yeast multidrug transporter Pdr5. AB - ATP-binding cassette multidrug efflux pumps transport a wide range of substrates. Current models suggest that a drug binds relatively tightly to a transport site in the transmembrane domains when the protein is in the closed inward facing conformation. Upon binding of ATP, the transporter can switch to an outward facing (drug off or drug releasing) structure of lower affinity. ATP hydrolysis is critically important for remodeling the drug-binding site to facilitate drug release and to reset the transporter for a new transport cycle. We characterized the novel phenotype of an S1368A mutant that lies in the putative drug-binding pocket of the yeast multidrug transporter Pdr5. This substitution created broad, severe drug hypersensitivity, although drug binding, ATP hydrolysis, and intradomain signaling were indistinguishable from the wild-type control. Several different rhodamine 6G efflux and accumulation assays yielded evidence consistent with the possibility that Ser-1368 prevents reentry of the excluded drug. PMID- 25112866 TI - Oligomeric state of purified transient receptor potential melastatin-1 (TRPM1), a protein essential for dim light vision. AB - Transient receptor potential melastatin-1 (TRPM1) is essential for the light induced depolarization of retinal ON bipolar cells. TRPM1 likely forms a multimeric channel complex, although almost nothing is known about the structure or subunit composition of channels formed by TRPM1 or any of its close relatives. Recombinant TRPM1 was robustly expressed in insect cells, but only a small fraction was localized to the plasma membrane. Similar intracellular localization was observed when TRPM1 was heterologously expressed in mammalian cells. TRPM1 was affinity-purified from Sf9 cells and complexed with amphipol, followed by detergent removal. In blue native gels and size exclusion chromatography, TRPM1 migrated with a mobility consistent with detergent- or amphipol-bound dimers. Cross-linking experiments were also consistent with a dimeric subunit stoichiometry, and cryoelectron microscopy and single particle analysis without symmetry imposition yielded a model with approximate 2-fold symmetrical features. Finally, electron microscopy of TRPM1-antibody complexes revealed a large particle that can accommodate TRPM1 and two antibody molecules. Taken together, these data indicate that purified TRPM1 is mostly dimeric. The three-dimensional structure of TRPM1 dimers is characterized by a small putative transmembrane domain and a larger domain with a hollow cavity. Blue native gels of solubilized mouse retina indicate that TRPM1 is present in two distinct complexes: one similar in size to the recombinant protein and one much larger. Because dimers are likely not functional ion channels, these results suggest that additional partner subunits participate in forming the transduction channel required for dim light vision and the ON pathway. PMID- 25112869 TI - The role of constitutive nitric-oxide synthase in ultraviolet B light-induced nuclear factor kappaB activity. AB - NF-kappaB is a transcription factor involved in many signaling pathways that also plays an important role in UV-induced skin tumorigenesis. UV radiation can activate NF-kappaB, but the detailed mechanism remains unclear. In this study, we provided evidence that the activation of constitutive nitric-oxide synthase plays a role in regulation of IkappaB reduction and NF-kappaB activation in human keratinocyte HaCaT cells in early phase (within 6 h) post-UVB. Treating the cells with l-NAME, a selective inhibitor of constitutive nitric-oxide synthase (cNOS), can partially reverse the IkappaB reduction and inhibit the DNA binding activity as well as nuclear translocation of NF-kappaB after UVB radiation. A luciferase reporter assay indicates that UVB-induced NF-kappaB activation is totally diminished in cNOS null cells. The cNOS-mediated reduction of IkappaB is likely due to the imbalance of nitric oxide/peroxynitrite because treating the cells with lower (50 MUm), but not higher (100-500 MUm), concentration of S-nitroso-N acetylpenicillamine (SNAP) can reverse the effect of l-NAME in partial restore IkappaB level post-UVB. Our data also showed that NF-kappaB activity was required for maintaining a stable IkappaB kinase alpha subunit (IKKalpha) level because treating the cells with NF-kappaB or cNOS inhibitors could reduce IKKalpha level upon UVB radiation. In addition, our data demonstrated that although NF-kappaB protects cells from UVB-induced death, its pro-survival activity was likely neutralized by the pro-death activity of peroxynitrite after UVB radiation. PMID- 25112868 TI - Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17/Treg cell balance. AB - Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a group of autoimmune diseases characterized by nonspecific inflammation in the gastrointestinal tract. Recent investigations suggest that activation of Th17 cells and/or deficiency of regulatory T cells (Treg) is involved in the pathogenesis of IBD. Heme oxygenase (HO)-1 is a protein with a wide range of anti-inflammatory and immune regulatory function, which exerts significantly protective roles in various T cell-mediated diseases. In this study, we aim to explore the immunological regulation of HO-1 in the dextran sulfate sodium-induced model of experimental murine colitis. BALB/c mice were administered 4% dextran sulfate sodium orally; some mice were intraperitoneally pretreated with HO-1 inducer hemin or HO-1 inhibitor stannum protoporphyrin IX. The results show that hemin enhances the colonic expression of HO-1 and significantly ameliorates the symptoms of colitis with improved histological changes, accompanied by a decreased proportion of Th17 cells and increased number of Tregs in mesenteric lymph node and spleen. Moreover, induction of HO-1 down regulates retinoic acid-related orphan receptor gammat expression and IL-17A levels, while promoting Treg-related forkhead box p3 (Foxp3) expression and IL-10 levels in colon. Further study in vitro revealed that up-regulated HO-1 switched the naive T cells to Tregs when cultured under a Th17-inducing environment, which involved in IL-6R blockade. Therefore, HO-1 may exhibit anti-inflammatory activity in the murine model of acute experimental colitis via regulating the balance between Th17 and Treg cells, thus providing a possible novel therapeutic target in IBD. PMID- 25112870 TI - Thrombin cleavage of osteopontin disrupts a pro-chemotactic sequence for dendritic cells, which is compensated by the release of its pro-chemotactic C terminal fragment. AB - Thrombin cleavage alters the function of osteopontin (OPN) by exposing an integrin binding site and releasing a chemotactic C-terminal fragment. Here, we examined thrombin cleavage of OPN in the context of dendritic cell (DC) migration to define its functional domains. Full-length OPN (OPN-FL), thrombin-cleaved N terminal fragment (OPN-R), thrombin- and carboxypeptidase B2-double-cleaved N terminal fragment (OPN-L), and C-terminal fragment (OPN-CTF) did not have intrinsic chemotactic activity, but all potentiated CCL21-induced DC migration. OPN-FL possessed the highest potency, whereas OPNRAA-FL had substantially less activity, indicating the importance of RGD. We identified a conserved (168)RSKSKKFRR(176) sequence on OPN-FL that spans the thrombin cleavage site, and it demonstrated potent pro-chemotactic effects on CCL21-induced DC migration. OPN FLR168A had reduced activity, and the double mutant OPNRAA-FLR168A had even lower activity, indicating that these functional domains accounted for most of the pro chemotactic activity of OPN-FL. OPN-CTF also possessed substantial pro chemotactic activity, which was fully expressed upon thrombin cleavage and its release from the intact protein, because OPN-CTF was substantially more active than OPNRAA-FLR168A containing the OPN-CTF sequence within the intact protein. OPN-R and OPN-L possessed similar potency, indicating that the newly exposed C terminal SVVYGLR sequence in OPN-R was not involved in the pro-chemotactic effect. OPN-FL and OPN-CTF did not directly bind to the CD44 standard form or CD44v6. In conclusion, thrombin cleavage of OPN disrupts a pro-chemotactic sequence in intact OPN, and its loss of pro-chemotactic activity is compensated by the release of OPN-CTF, which assumes a new conformation and possesses substantial activity in enhancing chemokine-induced migration of DCs. PMID- 25112871 TI - Angiotensin type 2 receptor signaling in satellite cells potentiates skeletal muscle regeneration. AB - Patients with advanced congestive heart failure (CHF) or chronic kidney disease (CKD) often have increased angiotensin II (Ang II) levels and cachexia. Ang II infusion in rodents causes sustained skeletal muscle wasting and decreases muscle regenerative potential through Ang II type 1 receptor (AT1R)-mediated signaling, likely contributing to the development of cachexia in CHF and CKD. However, the potential role of Ang II type 2 receptor (AT2R) signaling in skeletal muscle physiology is unknown. We found that AT2R expression was increased robustly in regenerating skeletal muscle after cardiotoxin (CTX)-induced muscle injury in vivo and differentiating myoblasts in vitro, suggesting that the increase in AT2R played an important role in regulating myoblast differentiation and muscle regeneration. To determine the potential role of AT2R in muscle regeneration, we infused C57BL/6 mice with the AT2R antagonist PD123319 during CTX-induced muscle regeneration. PD123319 reduced the size of regenerating myofibers and expression of the myoblast differentiation markers myogenin and embryonic myosin heavy chain. On the other hand, AT2R agonist CGP42112 infusion potentiated CTX injury induced myogenin and embryonic myosin heavy chain expression and increased the size of regenerating myofibers. In cultured myoblasts, AT2R knockdown by siRNA suppressed myoblast differentiation marker expression and myoblast differentiation via up-regulation of phospho-ERK1/2, and ERK inhibitor treatment completely blocked the effect of AT2R knockdown. These data indicate that AT2R signaling positively regulates myoblast differentiation and potentiates skeletal muscle regenerative potential, providing a new therapeutic target in wasting disorders such as CHF and CKD. PMID- 25112872 TI - Glutathionylation of the aquaporin-2 water channel: a novel post-translational modification modulated by the oxidative stress. AB - Aquaporin-2 (AQP2) is the vasopressin-regulated water channel that controls renal water reabsorption and urine concentration. AQP2 undergoes different regulated post-translational modifications, including phosphorylation and ubiquitylation, which are fundamental for controlling AQP2 cellular localization, stability, and function. The relationship between AQP2 and S-glutathionylation is of potential interest because reactive oxygen species (ROS), produced under renal failure or nephrotoxic drugs, may influence renal function as well as the expression and the activity of different transporters and channels, including aquaporins. Here, we show for the first time that AQP2 is subjected to S-glutathionylation in kidney and in HEK-293 cells stably expressing AQP2. S-Glutathionylation is a redox dependent post-translational modification controlling several signal transduction pathways and displaying an acute effect on free cytosolic calcium concentration. Interestingly, we found that in fresh kidney slices, the increased AQP2 S glutathionylation correlated with tert-butyl hydroperoxide-induced ROS generation. Moreover, we also found that cells expressing wild-type human calcium sensing receptor (hCaSR-wt) and its gain of function (hCaSR-R990G; hCaSR-N124K) had a significant decrease in AQP2 S-glutathionylation secondary to reduced ROS levels and reduced basal intracellular calcium concentration compared with mock cells. Together, these new findings provide fundamental insight into cell biological aspects of AQP2 function and may be relevant to better understand and explain pathological states characterized by an oxidative stress and AQP2 dependent water reabsorption disturbs. PMID- 25112873 TI - Diacylglycerol kinase delta phosphorylates phosphatidylcholine-specific phospholipase C-dependent, palmitic acid-containing diacylglycerol species in response to high glucose levels. AB - Decreased expression of diacylglycerol (DG) kinase (DGK) delta in skeletal muscles is closely related to the pathogenesis of type 2 diabetes. To identify DG species that are phosphorylated by DGKdelta in response to high glucose stimulation, we investigated high glucose-dependent changes in phosphatidic acid (PA) molecular species in mouse C2C12 myoblasts using a newly established liquid chromatography/MS method. We found that the suppression of DGKdelta2 expression by DGKdelta-specific siRNAs significantly inhibited glucose-dependent increases in 30:0-, 32:0-, and 34:0-PA and moderately attenuated 30:1-, 32:1-, and 34:1-PA. Moreover, overexpression of DGKdelta2 also enhanced the production of these PA species. MS/MS analysis revealed that these PA species commonly contain palmitic acid (16:0). D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), significantly inhibited the glucose-stimulated production of the palmitic acid-containing PA species. Moreover, PC-PLC was co-immunoprecipitated with DGKdelta2. These results strongly suggest that DGKdelta preferably metabolizes palmitic acid-containing DG species supplied from the PC-PLC pathway, but not arachidonic acid (20:4)-containing DG species derived from the phosphatidylinositol turnover, in response to high glucose levels. PMID- 25112875 TI - The roles of the RIIbeta linker and N-terminal cyclic nucleotide-binding domain in determining the unique structures of the type IIbeta protein kinase A: a small angle x-ray and neutron scattering study. AB - Protein kinase A (PKA) is ubiquitously expressed and is responsible for regulating many important cellular functions in response to changes in intracellular cAMP concentrations. The PKA holoenzyme is a tetramer (R2:C2), with a regulatory subunit homodimer (R2) that binds and inhibits two catalytic (C) subunits; binding of cAMP to the regulatory subunit homodimer causes activation of the catalytic subunits. Four different R subunit isoforms exist in mammalian cells, and these confer different structural features, subcellular localization, and biochemical properties upon the PKA holoenzymes they form. The holoenzyme containing RIIbeta is structurally unique in that the type IIbeta holoenzyme is much more compact than the free RIIbeta homodimer. We have used small angle x-ray scattering and small angle neutron scattering to study the solution structure and subunit organization of a holoenzyme containing an RIIbeta C-terminal deletion mutant (RIIbeta(1-280)), which is missing the C-terminal cAMP-binding domain to better understand the structural organization of the type IIbeta holoenzyme and the RIIbeta domains that contribute to stabilizing the holoenzyme conformation. Our results demonstrate that compaction of the type IIbeta holoenzyme does not require the C-terminal cAMP-binding domain but rather involves large structural rearrangements within the linker and N-terminal cyclic nucleotide-binding domain of the RIIbeta homodimer. The structural rearrangements are significantly greater than seen previously with RIIalpha and are likely to be important in mediating short range and long range interdomain and intersubunit interactions that uniquely regulate the activity of the type IIbeta isoform of PKA. PMID- 25112874 TI - Chemotherapeutic drugs induce ATP release via caspase-gated pannexin-1 channels and a caspase/pannexin-1-independent mechanism. AB - Anti-tumor immune responses have been linked to the regulated release of ATP from apoptotic cancer cells to engage P2 purinergic receptor signaling cascades in nearby leukocytes. We used the Jurkat T cell acute lymphocytic leukemia model to characterize the role of pannexin-1 (Panx1) channels in the release of nucleotides during chemotherapeutic drug-induced apoptosis. Diverse pro-apoptotic drugs, including topoisomerase II inhibitors, kinase inhibitors, and proteosome inhibitors, induced functional activation of Panx1 channels via caspase-3 mediated cleavage of the Panx1 autoinhibitory C-terminal domain. The caspase activated Panx1 channels mediated efflux of ATP, but also ADP and AMP, with the latter two comprising >90% of the released adenine nucleotide pool as cells transitioned from the early to late stages of apoptosis. Chemotherapeutic drugs also activated an alternative caspase- and Panx1-independent pathway for ATP release from Jurkat cells in the presence of benzyloxycarbonyl-VAD, a pan-caspase inhibitor. Comparison of Panx1 levels indicated much higher expression in leukemic T lymphocytes than in normal, untransformed T lymphoblasts. This suggests that signaling roles for Panx1 may be amplified in leukemic leukocytes. Together, these results identify chemotherapy-activated pannexin-1 channels and ATP release as possible mediators of paracrine interaction between dying tumor cells and the effector leukocytes that mediate immunogenic anti-tumor responses. PMID- 25112876 TI - Identification of key residues determining isomerohydrolase activity of human RPE65. AB - RPE65 is the retinoid isomerohydrolase that converts all-trans-retinyl ester to 11-cis-retinol, a key reaction in the retinoid visual cycle. We have previously reported that cone-dominant chicken RPE65 (cRPE65) shares 90% sequence identity with human RPE65 (hRPE65) but exhibits substantially higher isomerohydrolase activity than that of bovine RPE65 or hRPE65. In this study, we sought to identify key residues responsible for the higher enzymatic activity of cRPE65. Based on the amino acid sequence comparison of mammalian and other lower vertebrates' RPE65, including cone-dominant chicken, 8 residues of hRPE65 were separately replaced by their counterparts of cRPE65 using site-directed mutagenesis. The enzymatic activities of cRPE65, hRPE65, and its mutants were measured by in vitro isomerohydrolase activity assay, and the retinoid products were analyzed by HPLC. Among the mutants analyzed, two single point mutants, N170K and K297G, and a double mutant, N170K/K297G, of hRPE65 exhibited significantly higher catalytic activity than WT hRPE65. Further, when an amino terminal fragment (Met(1)-Arg(33)) of the N170K/K297G double mutant of hRPE65 was replaced with the corresponding cRPE65 fragment, the isomerohydrolase activity was further increased to a level similar to that of cRPE65. This finding contributes to the understanding of the structural basis for isomerohydrolase activity. This highly efficient human isomerohydrolase mutant can be used to improve the efficacy of RPE65 gene therapy for retinal degeneration caused by RPE65 mutations. PMID- 25112877 TI - p53 is required for cisplatin-induced processing of the mitochondrial fusion protein L-Opa1 that is mediated by the mitochondrial metallopeptidase Oma1 in gynecologic cancers. AB - Mitochondria are highly dynamic organelles, and mitochondrial fission is a crucial step of apoptosis. Although Oma1 is believed to be responsible for long form Opa1 (L-Opa1) processing during mitochondrial fragmentation, whether and how Oma1 is involved in L-Opa1 processing and participates in the regulation of chemoresistance is unknown. Chemosensitive and chemoresistant ovarian (OVCA) and cervical (CECA) cancer cells were treated with cisplatin (CDDP). Mitochondrial dynamics and protein contents were assessed by immunofluorescence and Western blot, respectively. The requirements of Oma1 and p53 for CDDP-induced L-Opa1 processing, mitochondrial fragmentation, and apoptosis were examined by siRNA or cDNA. CDDP induces L-Opa1 processing and mitochondrial fragmentation in chemosensitive but not in chemoresistant cells. CDDP induced Oma1 40-kDa form increases in OV2008 cells, not in C13* cells. Oma1 knockdown inhibited L-Opa1 processing, mitochondrial fragmentation, and apoptosis. Silencing p53 expression attenuated the effects of CDDP in Oma1 (40 kDa) increase, L-Opa1 processing, mitochondrial fragmentation, and apoptosis in chemosensitive OVCA cells, whereas reconstitution of p53 in p53 mutant or null chemoresistant OVCA cells induced Oma1 (40 kDa) increase, L-Opa1 processing, mitochondrial fragmentation, and apoptosis irrespective of the presence of CDDP. Prohibitin 1 (Phb1) dissociates from Opa1-Phb1 complex and binds phosphorylated p53 (serine 15) in response to CDDP in chemosensitive but not chemoresistant CECA cells. These findings demonstrate that (a) p53 and Oma1 mediate L-Opa1 processing, (b) mitochondrial fragmentation is involved in CDDP-induced apoptosis in OVCA and CECA cells, and (c) dysregulated mitochondrial dynamics may in part be involved in the pathophysiology of CDDP resistance. PMID- 25112879 TI - A revision of Metaleptobasis Calvert (Odonata: Coenagrionidae) with seven synonymies and the description of eighteen new species from South America. AB - Examination of over 1,400 specimens of the neotropical genus Metaleptobasis Calvert, 1907, including primary types or paratypes of 18 of the 20 currently available species names and large series of specimens including pairs in tandem and copula, allowed me to unequivocally associate older names with species, distinguish between specific and intraspecific variability, associate both sexes for each species, and recognize the existence of female polymorphism. As a result, seven names are found to be junior synonyms: Metaleptobasis mauritia Williamson, 1915 junior synonym of M. bicornis (Selys, 1877), M. manicaria Williamson, 1915 and M. fernandezi Racenis, 1955 junior synonyms of M. diceras (Selys, 1877), M. westfalli Cumming, 1954 junior synonym of M. foreli Ris, 1915, and M. tetragena Calvert, 1947, M. weibezahni Racenis, 1955, and M. incisula De Marmels, 1989 junior synonyms of M. brysonima Williamson, 1915. Lectotypes are designated for M. amazonica and Leptobasis diceras. Eighteen new species of Metaleptobasis are described: M. brevicauda (Holotype ?, Peru, Huanuco Dep., Shapajilla, jungle, 11 v 1939, F. Woytkowski leg., in UMMZ); M. falcifera (Holotype ?, Peru, Madre De Dios Dep., Pakitza, Reserved Zone, Manu National Park, T2 to R2 to T1 to base camp, 11 degrees 55'48''S, 71 degrees 15'18''W, 250 m, 17 ix 1989, J.A. Louton leg., in USNM); M. furcifera (Holotype ?, Peru, Loreto Dep., Iquitos, iii 1936, G.G. Klug leg., in BMNH); M. gabrielae (Holotype ?, Peru, Loreto Dep., Tamshiyacu-Tahuayo Reserve, forest interior (4 degrees 23'40''S, 73 degrees 14'56''W), 27 vii 2009, T. Faasen leg., in RMNH); M. guillermoi (Holotype ?, Peru, Loreto Dep., Yarinacocha, temporary forest stream (8 degrees 17'S, 74 degrees 37'W, 145 m), 2 vi 1972, D.L. Pearson leg., in FSCA); M. inermis (Holotype ?, Brazil, Para State, Jacareacanga, vii 1969, F.R. Barbosa leg., in UMMZ); M. leniloba (Holotype ?, Peru, Loreto Dep., Pacaya-Samiria National Reserve, Santa Luisa trail (5 degrees 15'S, 74 degrees 40'W), 10 vi 2008, C. Beatty, A. Cordero & J. Hoffmann leg., in FSCA); M. longicauda (Holotype ?, Brazil, Mato Grosso State, C. Teles Pires, Alto Tapajos, 1-31 viii 1956, Sick leg., in MNRJ); M. orthogonia (Holotype ?, Peru, Loreto Dep., San Juan, Rio Amazonas, near Iquitos, viii 1939, J. Schunke leg., in FSCA); M. paludicola (Holotype ?, Peru, Loreto Dep., Tamshiyacu-Tahuayo Reserve, swamp, 4 degrees 23'49''S, 73 degrees 14'57''W, 27 ii 2009, T. Faasen leg., in RMNH); M. panguanae (Holotype ?, Peru, Huanuco Dep., Biological Station Panguana, E side Rio Yuyapichis, 9 degrees 37'S, 74 degrees 57'W, 6-17 iv 2003, H.J. & E.-G. Burmeister leg., in ZSM); M. peltata (Holotype ?, Peru Loreto Dep., Tamshiyacu Tahuayo Reserve, 4 degrees 21'22''S, 73 degrees 11'0''W, 19 ii 2010, T. Faasen leg., in RMNH); M. prostrata (Holotype ?, Peru, Junin Dep., Satipo, v 1945, P. Paprzycki leg., in UMMZ); M. silvicola (Holotype ?, Peru, Madre de Dios Dep., Explorer's Inn on Rio Tambopata, 30 km SW Puerto Maldonado, main trail, 1 viii 1979, M. Perkins & P. Donahue leg., in FSCA); M. spatulata (Holotype ?, Peru, Huanuco Dep., 10 km N of Cucharas, confluence of Huallaga and Pacay rivers, viii 1954, F. Woytkowski leg., in UMMZ); M. tridentigera (Holotype ?, Brazil, Rondonia State, Porto Velho, Area Abunan, T11 Aleatorio, 8 degrees 46'S, 63 degrees 54'W, 86 m, 16 v 2010, Nogueira & Mendes leg., in MZUSP); M. truncata (Holotype ?, Brazil, Para State, Jacareacanga, xi 1969, F.R. Barbosa leg., in UMMZ); and M. turbinata (Holotype ?, Peru, Loreto Dep., Tamshiyacu-Tahuayo Reserve, forest swamp (4 degrees 24'18''S, 73 degrees 14'38''W), 25 ii 2010, T. Fassen leg., in RMNH). Illustrations, keys, diagnoses, and distribution maps for all 31 currently known species are provided. Phylogenetic relationships within the genus Metaleptobasis are analyzed based on 33 adult morphological characters, including the 31 currently described species of Metaleptobasis and eleven outgroup taxa of other Coenagrionidae of the subfamily Teinobasinae. The cladistic analysis recovered Metaleptobasis as monophyletic, and as sister group of Aceratobasis Kennedy, a teinobasine genus some of the species of which possess an articulated spur on base of male cercus. Hypothesized relationships among its species are discussed. PMID- 25112880 TI - Swedish Plectida (Nematoda). Part 4. The genus Leptolaimus de Man, 1876. AB - Twelve known and nine new species of Leptolaimus are described from bottom sediments collected in marine habitats of Sweden, including the Bothnian Sea and Bothnian Bay, the Baltic Sea proper, Gullmarn Fjord and the Skagerrak. Three of these species have been previously recorded in Sweden while nine are new records for the Swedish fauna. The following known species are redescribed: Leptolaimus papilliger de Man, 1876, L. cupulatus Lorenzen, 1972, L. danicus Jensen, 1978, L. donsi (Allgen, 1946) comb. n., L. mixtus Lorenzen, 1972, L. pellucidus (Southern, 1914) comb. n., L. venustus Lorenzen, 1972, L. lorenzeni (Boucher & de Bovee, 1972) comb. n., L. alatus Vitiello, 1971, L. macer Lorenzen, 1972, L. septempapillatus Platt, 1973, L. elegans (Schuurmans Stekhoven & De Coninck, 1933) Gerlach, 1958. Leptolaimus primus sp. n. is characterised by the 319-472 um long body; rounded labial region continuous with body contour; cephalic setae 1.5 2.0 um long; amphid located 7.0-11.5 um from anterior end; first body pore located 18.5-28.0 um from anterior end; lateral field originating 35 um from anterior end; female without supplements, vagina without pars refringens, vulva midventral; male without tubular and with four alveolar supplements, alveolar supplements without sclerotized inner ring; spicules arcuate and 13.5-16.0 um long. Leptolaimus secundus sp. n. is characterised by the 576-645 um long body; rounded labial region continuous with body contour; cephalic setae 2.0 um long; amphid located 6.5-7.0 um from anterior end; first body pore located 23.0-28.5 um from anterior end; lateral field originating 18.0-23.0 um from anterior end; female without supplements, vagina without pars refringens, vulva midventral; male with single tubular and 9-15 alveolar supplements, tubular supplement weakly arcuate with blunt tips, alveolar supplements with sclerotized lining; spicules arcuate and 23.0-26.5 um long. Leptolaimus tertius sp. n. is characterised by the 576-579 um long body; rounded labial region continuous with body contour; cephalic setae 2 um long; amphid located 4-5 um from anterior end; first body pore located 21.0-23.5 um from anterior end; lateral field originating 26-29 um from anterior end; male with four tubular and 7-10 alveolar supplements, tubular supplements weakly arcuate with blunt tips, alveolar supplements with sclerotized inner ring; spicules arcuate and 25-26 um long. Leptolaimus quartus sp. n. is characterised by the 597-686 mm long body; rounded labial region continuous with body contour; cephalic setae 2.0-3.5 um long; amphid located 5.0-7.0 um from anterior end; first body pore located 23.5-27.0 um from anterior end; lateral field originating 19.0-27.0 um from anterior end; male with three tubular and 8-9 alveolar supplements, tubular supplements straight with blunt expanded tips, alveolar supplements with sclerotized inner ring; spicules arcuate and 23.0-25.0 um long. Leptolaimus quintus sp. n. is characterised by the 443-528 um long body; rounded labial region continuous with body contour; cephalic setae 1.0-2.0 um long; amphid located 7.0-10.0 um from anterior end; first body pore located 18.0 28.5 um from anterior end; lateral field originating 25.0-41.0 um from anterior end; female with two tubular supplements (one just posterior to cardia and one in front of anus), vagina without pars refringens, vulva right-sublateral; male with 8-10 tubular and without alveolar supplements, tubular supplements weakly arcuate with anchor-like tips; spicules arcuate and 17.0-22.0 um long. Leptolaimus sextus sp. n. is characterised by the 626-728 um long body; truncated labial region offset from body contour; cephalic setae 1.5-2.0 um long; amphid located 8.0-12.0 um from anterior end; first body pore located 41.0-48.5 um from anterior end; lateral field originating 28.0-41.0 um from anterior end; female without supplements, vagina without pars refringens, vulva midventral; male with five (rarely six) tubular and without alveolar supplements, tubular supplements weakly S-shaped with bifid tips; spicules arcuate and 39.0-46.0 um long. Leptolaimus septimus sp. n. is characterised by the 679-850 um long body; truncate labial region offset from body contour; cephalic setae 2.5-3.5 um long; amphid located 8.5-11.5 um from anterior end; first body pore located 37.0-44.0 um from anterior end; lateral field originating 26.5-37.0 um from anterior end; female without supplements, vagina without pars refringens, vulva midventral; male with four (rarely five) tubular and without alveolar supplements, tubular supplements weakly S-shaped, with bifid or blunt tips; spicules arcuate and 31.0-33.5 um long. Leptolaimus octavus sp. n. is characterised by the 541-638 um long body; truncate labial region continuous with body contour; cephalic setae 1.5-2.0 um long; amphid located 8.5-12.0 um from anterior end; first body pore located 31.5 41.0 um from anterior end; lateral field originating 26.0-40.0 um from anterior end and expanding into bursa-like structures along the tail; female without supplements, vagina without pars refringens, vulva midventral; male with four tubular and without alveolar supplements, tubular supplements weakly S-shaped with dentate tips; spicules arcuate and 30.0-31.5 um long. Leptolaimus nonus sp. n. is characterised by the 403-633 um long body; rounded labial region continuous with body contour; cephalic setae 1.5-3.0 um long; amphid located 8.0-10.0 um from anterior end; first body pore located 16.5-29.0 um from anterior end; lateral field originating 47.0-99.0 um from anterior end and expanding into bursa like structures along the proximal part of the tail; female without supplements, vagina with bacilliform pars refringens, vulva right-subventral; male with 4-5 tubular and without alveolar supplements, tubular supplements weakly arcuate with dentate tips; spicules arcuate and 17.0-26.0 um long. The following nomenclatorial changes are proposed: Eutelolaimus donsi Allgen, 1947 is transferred to the genus Leptolaimus, as L. donsi (Allgen, 1947) comb. n.; Halaphanolaimus cangionensis Gagarin & Nguyen Vu Thanh, 2007 is transferred to the genus Leptolaimus, as L. cangionensis (Gagarin & Nguyen Vu Thanh, 2007) comb. n.; Halaphanolaimus harpaga Boucher & de Bovee, 1972 is transferred to the genus Leptolaimus, as L. harpaga (Boucher & de Bovee, 1972) comb. n.; Halaphanolaimus lorenzeni Boucher & de Bovee, 1972 is transferred to the genus Leptolaimus, as L. lorenzeni (Boucher & de Bovee, 1972) comb. n.; Halaphanolaimus pellucidus Southern, 1914 is transferred to the genus Leptolaimus, as L. pellucidus (Southern, 1914) comb. n.; Halaphanolaimus rivalis Gagarin & Nguyen Vu Thanh, 2007 is transferred to the genus Leptolaimus, as L. rivalis (Gagarin & Nguyen Vu Thanh, 2007) comb. n.; Halaphanolaimus marinus Kamran, Nasira & Shahina, 2010 is transferred to the genus Leptolaimus as L. marinus (Kamran, Nasira & Shahina, 2010) comb. n. and considered a junior synonym of Leptolaimus rivalis (Gagarin & Nguyen Vu Thanh, 2007) comb. n.; Halaphanolaimus sergeevae Urkmez & Brennan, 2013 is transferred to the genus Leptolaimus as L. sergeevae (Urkmez & Brennan, 2013) comb. n.; Leptolaimus vitielloi nom. nov. is proposed for Leptolaimus minutus Vitiello, 1971 nec L. minutus (Schuurmans Stekhoven, 1942) comb. n.; Polylaimium exile Cobb, 1920 is transferred to the genus Leptolaimus, as L. exilis (Cobb, 1920) comb. n. and is considered species inquirendae. A taxonomic review, tabular compendium and identification key for species of the genus Leptolaimus are also given. PMID- 25112881 TI - An updated host-parasite catalogue of world Dryinidae (Hymenoptera: Chrysidoidea). AB - An updated host-parasite catalogue of world Dryinidae is presented. The catalogue presents 1014 relationships between dryinids and their hosts checked in 84 countries of the world, including 38 new records. PMID- 25112878 TI - Proline biosynthesis is required for endoplasmic reticulum stress tolerance in Saccharomyces cerevisiae. AB - The amino acid proline is uniquely involved in cellular processes that underlie stress response in a variety of organisms. Proline is known to minimize protein aggregation, but a detailed study of how proline impacts cell survival during accumulation of misfolded proteins in the endoplasmic reticulum (ER) has not been performed. To address this we examined in Saccharomyces cerevisiae the effect of knocking out the PRO1, PRO2, and PRO3 genes responsible for proline biosynthesis. The null mutants pro1, pro2, and pro3 were shown to have increased sensitivity to ER stress relative to wild-type cells, which could be restored by proline or the corresponding genetic complementation. Of these mutants, pro3 was the most sensitive to tunicamycin and was rescued by anaerobic growth conditions or reduced thiol reagents. The pro3 mutant cells have higher intracellular reactive oxygen species, total glutathione, and a NADP(+)/NADPH ratio than wild-type cells under limiting proline conditions. Depletion of proline biosynthesis also inhibits the unfolded protein response (UPR) indicating proline protection involves the UPR. To more broadly test the role of proline in ER stress, increased proline biosynthesis was shown to partially rescue the ER stress sensitivity of a hog1 null mutant in which the high osmolality pathway is disrupted. PMID- 25112882 TI - Outcomes of infrainguinal revascularizations with endovascular first strategy in critical limb ischemia. AB - PURPOSE: This study was designed to study the outcome of infrainguinal revascularization in patients with critical limb ischemia (CLI) in an institution with a preference towards endovascular intervention first in patients with poor condition, unfavourable anatomy for surgery, no venous material for bypass, and old age. METHODS: A prospective, observational cohort study was conducted between May 2007 and May 2010 in patients presenting with CLI. At baseline, the optimal treatment was selected, i.e., endovascular or surgical treatment. In case of uncertainty about the preferred treatment, a multidisciplinary team (MDT) was consulted. Primary endpoints were quality of life and functional status 6 and 12 months after initial intervention, assessed by the VascuQol and AMC Linear Disability Score questionnaires, respectively. RESULTS: In total, 113 patients were included; 86 had an endovascular intervention and 27 had surgery. During follow-up, 41 % underwent an additional ipsilateral revascularisation procedure. For the total population, and endovascular and surgery subgroups, the VascuQol sum scores improved after 6 and 12 months (p < 0.01 for all outcomes) compared with baseline. The functional status improved (p = 0.043) after 12 months compared with baseline for the total population. Functional status of the surgery subgroup improved significantly after 6 (p = 0.031) and 12 (p = 0.044) months, but not that of the endovascular subgroup. CONCLUSIONS: Overall, the strategy of performing endovascular treatment first in patients with poor condition, unfavourable anatomy for surgery, no venous material for bypass, and old age has comparable or even slightly better results compared with the BASIL trial and other cohort studies. All vascular groups should discuss whether their treatment strategy should be directed at treating CLI patients preferably endovascular first and consider implementing an MDT to optimize patient outcomes. PMID- 25112883 TI - Chemical renal denervation by vincristine: the role of the flow rate of delivery. AB - PURPOSE: Vincristine has been proven promising regarding its safety and efficacy for the renal artery denervation both in experimental models and in humans. The aim of the study was to compare in an experimental model the efficacy of constant versus random flow rate delivery of vincristine on renal sympathetic denervation. METHODS: We used 10 juvenile Landrace swine. After the introduction of a 7F sheath into the femoral artery, a guide wire was advanced into the distal part of the renal artery. Then the first delivery balloon catheter, which delivers vincristine in random flow rate, was advanced at the proximal part of the artery, and the balloon was inflated in order to locally deliver vincristine to the media of the renal artery. The process was repeated in the contralateral renal artery, with the use of the double balloon catheter that delivers vincristine with a constant flow rate. Euthanasia of the animals was performed at 28 days. All sections were processed for histological and immunohistochemical analysis. RESULTS: The delivery of vincristine with both catheters was successful and uncomplicated. Immunohistochemistry showed that the mean number of intact nerves in all sections was significantly lower in the group of vincristine delivered with constant flow catheter compared to the group that the delivery was performed in a random fashion. (1.48 +/- 0.37 vs. 1.70 +/- 0.41, p = 0.04). CONCLUSION: Chemical renal denervation with vincristine by a constant flow rate catheter is more effective compared to the denervation performed by a catheter that delivers vincristine in a random fashion. PMID- 25112884 TI - Neurotensin--regulated miR-133alpha is involved in proinflammatory signalling in human colonic epithelial cells and in experimental colitis. AB - OBJECTIVE: Neurotensin (NT) mediates colonic inflammation through its receptor neurotensin receptor 1 (NTR1). NT stimulates miR-133alpha expression in colonic epithelial cells. We investigated the role of miR-133alpha in NT-associated colonic inflammation in vitro and in vivo. DESIGN: miR-133alpha and aftiphilin (AFTPH) levels were measured by quantitative PCR. Antisense (as)-miR-133alpha was administrated intracolonicaly prior to induction of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis and dextran sodium sulfate (DSS)-induced colitis. The effect of AFTPH was examined by gene silencing in vitro. RESULTS: NT increased miR-133alpha levels in NCM-460 overexpressing NTR1 (NCM460-NTR1) and HCT-116 cells. NT-induced p38, ERK1/2, c-Jun, and NF-kappaB activation, as well as IL-6, IL-8 and IL-1beta messenger RNA (mRNA) expression in NCM-460-NTR1 cells were reduced in miR-133alpha-silenced cells, while overexpression of miR-133alpha reversed these effects. MiR-133alpha levels were increased in TNBS (2 day) and DSS (5 day) colitis, while NTR1 deficient DSS-exposed mice had reduced miR 133alpha levels, compared to wild-type colitic mice. Intracolonic as-miR-133alpha attenuated several parameters of colitis as well expression of proinflammatory mediators in the colonic mucosa. In silico search coupled with qPCR identified AFTPH as a downstream target of miR-133alpha, while NT decreased AFTPH expression in NCM-460-NTR1 colonocytes. Gene silencing of AFTPH enhanced NT-induced proinflammatory responses and AFTPH levels were downregulated in experimental colitis. Levels of miR-133alpha were significantly upregulated, while AFTPH levels were downregulated in colonic biopsies of patients with ulcerative colitis compared to controls. CONCLUSIONS: NT-associated colitis and inflammatory signalling are regulated by miR-133alpha-AFTPH interactions. Targeting of miR 133alpha or AFTPH may represent a novel therapeutic approach in inflammatory bowel disease. PMID- 25112885 TI - Interrupted imino-Nazarov cyclization of 1-aminopentadienyl cation and related cascade process. AB - Facile 4pi conrotatory imino-Nazarov cyclization of a 1-aminopentadienyl cation generated from condensation an aldehyde and secondary aniline in the presence of a catalytic amount of a Lewis acid has been developed. Silver(I)-catalyzed intramolecular arene trapping of the resulting cyclic oxyallyl cation leads to formation of tricyclic indoline-fused cyclopentanone. The use of lanthanide salts allows transformation after the initial trapping to afford tetrahydroquinoline fused cyclopentenone in a concise manner. PMID- 25112886 TI - Hearing and age-related changes in the gray mouse lemur. AB - In order to examine auditory thresholds and hearing sensitivity during aging in the gray mouse lemur (Microcebus murinus), suggested to represent a model for early primate evolution and Alzheimer research, we applied brainstem-evoked response audiometry (BERA), traditionally used for screening hearing sensitivity in human babies. To assess the effect of age, we determined auditory thresholds in two age groups of adult mouse lemurs (young adults, 1-5 years; old adults, >=7 years) using clicks and tone pips. Auditory thresholds indicated frequency sensitivity from 800 Hz to almost 50 kHz, covering the species tonal communication range with fundamentals from about 8 to 40 kHz. The frequency of best hearing at 7.9 kHz was slightly lower than that and coincided with the dominant frequencies of communication signals of a predator. Aging shifted auditory thresholds in the range between 2 and 50.4 kHz significantly by 12-27 dB. This mild presbyacusis, expressed in a drop of amplitudes of BERA signals, but not discernible in latencies of responses, suggests a metabolic age-related decrease potentially combined with an accompanying degeneration of the cochlear nerve. Our findings on hearing range of this species support the hypothesis that predation was a driving factor for the evolution of hearing in small ancestral primates. Likewise, results provide the empirical basis for future approaches trying to differentiate peripheral from central factors when studying Alzheimer's disease-like pathologies in the aging brain. PMID- 25112888 TI - The Neurostimulation Appropriateness Consensus Committee. PMID- 25112887 TI - [Selective sentinel node biopsy in breast cancer with contralateral axillary drainage]. PMID- 25112889 TI - The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee. AB - INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. METHODS: The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. RESULTS: Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated. CONCLUSIONS: Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation. PMID- 25112890 TI - The appropriate use of neurostimulation: stimulation of the intracranial and extracranial space and head for chronic pain. Neuromodulation Appropriateness Consensus Committee. AB - INTRODUCTION: The International Neuromodulation Society (INS) has identified a need for evaluation and analysis of the practice of neurostimulation of the brain and extracranial nerves of the head to treat chronic pain. METHODS: The INS board of directors chose an expert panel, the Neuromodulation Appropriateness Consensus Committee (NACC), to evaluate the peer-reviewed literature, current research, and clinical experience and to give guidance for the appropriate use of these methods. The literature searches involved key word searches in PubMed, EMBASE, and Google Scholar dated 1970-2013, which were graded and evaluated by the authors. RESULTS: The NACC found that evidence supports extracranial stimulation for facial pain, migraine, and scalp pain but is limited for intracranial neuromodulation. High cervical spinal cord stimulation is an evolving option for facial pain. Intracranial neurostimulation may be an excellent option to treat diseases of the nervous system, such as tremor and Parkinson's disease, and in the future, potentially Alzheimer's disease and traumatic brain injury, but current use of intracranial stimulation for pain should be seen as investigational. CONCLUSIONS: The NACC concludes that extracranial nerve stimulation should be considered in the algorithmic treatment of migraine and other disorders of the head. We should strive to perfect targets outside the cranium when treating pain, if at all possible. PMID- 25112891 TI - The appropriate use of neurostimulation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain. Neuromodulation Appropriateness Consensus Committee. AB - INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes. METHODS: The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks. RESULTS: The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician. CONCLUSIONS: The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly. PMID- 25112893 TI - Paraneoplastic pemphigus associated with metastatic lymphoepithelioma-like carcinoma originating from the thyroid gland. PMID- 25112892 TI - The appropriate use of neurostimulation: new and evolving neurostimulation therapies and applicable treatment for chronic pain and selected disease states. Neuromodulation Appropriateness Consensus Committee. AB - INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need to provide an expert consensus that defines the appropriate use of neuromodulation technologies for appropriate patients. The Neuromodulation Appropriateness Consensus Committee (NACC) was formed to give guidance to current practice and insight into future developments. METHODS: The INS executive board selected members of the international scientific community to analyze scientific evidence for current and future innovations and to use clinical experience to fill in any gaps in information. The NACC used PubMed and Google Scholar to obtain current evidence in the field and used clinical and research experience to give a more complete picture of the innovations in the field. RESULTS: The NACC has determined that currently approved neurostimulation techniques and technologies have expanded our ability to treat patients in a more effective and specific fashion. Despite these advances, the NACC has identified several additional promising technologies and potential applications for neurostimulation that could move this field forward and expand the applicability of neuromodulation. CONCLUSIONS: The NACC concludes that the field of neurostimulation is an evolving and rapidly changing one that will lead to improved patient access, safety, and outcomes. PMID- 25112894 TI - The role of postnatal neurogenesis in supporting remote memory and spatial metric processing. AB - In this study, we determined the contribution of juvenile neurogenesis to the performance of mice on a remote memory for temporally based association task and in a novelty based spatial pattern separation task. This was accomplished by mating homozygous DNMT1-loxP mice with heterozygous GFAP-Cre mice and comparing Cre+ (no postnatal neurogenesis) to Cre- (wild type) littermate offspring. The results indicate that Cre+ mice are impaired relative to Cre- mice in the remote memory for a temporal based association task and in a novelty based spatial pattern separation task. These results support the temporal integration model of Aimone et al., [(2006) Nat Neurosci 9:723-727] and provide further support for an important role for postnatally born neurons in spatial pattern separation. In contrast, Cre+ mice are not impaired relative to Cre- mice in an object-context recognition task and a spatial location recognition task. These latter data suggest that postnatally derived neurons in the dentate gyrus (DG) do not support all spatial and object recognition functions of the DG. PMID- 25112895 TI - Antioxidant, antimicrobial and antiproliferative activities of Anthemis palestina essential oil. AB - BACKGROUND: Anthemis palestina (Asteraceae) extends across the Mediterranean region, southwest Asia and eastern Africa. Although traditionally used for several applications, in vitro investigation of biological functions associated with Anthemis palestina essential oil had never been reported. METHODS: The air dried flowers of Anthemis palestina were subjected to hydrodistillation to yield the oil. The antioxidant activity of the hydrodistilled oil was characterized using various in vitro model systems such as DPPH, ferric-reducing antioxidant power and hydroxyl radical scavenging activity. Antibacterial activity was tested against six bacterial species, representing both Gram positive and Gram negative bacteria. Antifungal activity was evaluated using three Candida species. The minimum inhibitory concentration (MIC) for each examined microorganism was determined using the microdilution method. The oil's antiproliferative effects against eight human cancer cell lines were also studied and the lethal doses that resulted in 50% reduction of cell viability (LD50) were determined. RESULTS: The results indicate that the essential oil of Anthemis palestina exhibited substantial antioxidant activities as demonstrated with DPPH, ferric reducing antioxidant power, and hydroxyl radical scavenging activity. In addition, a broad spectrum antibacterial activity of the oil was revealed with better susceptibility of Gram positive bacteria towards the oil. The MIC values ranged between 6-75 MUg/ml. Besides, the oil demonstrated a moderate inhibitory effect on the three Candida species examined; with MIC values ranging between 48-95 MUg/ml. Potent cytotoxic activities, especially against HeLa cell line; with LD50 of 32 MUg/ml, BJAB cell line; with LD50 of 57 MUg/ml, and Caco-2 cell line; with LD50 of 61 MUg/ml, were observed. CONCLUSION: The results obtained indicate high potential of Anthemis palestina essential oil as bioactive oil, for nutraceutical and medical applications, possessing antioxidant, antimicrobial and antiproliferative activities. PMID- 25112897 TI - History of corneal transplantation in Australia. AB - Corneal transplantation is a triumph of modern ophthalmology. The possibility of corneal transplantation was first raised in 1797 but a century passed before Zirm achieved the first successful penetrating graft in 1905. Gibson reported the first corneal graft in Australia from Brisbane in 1940 and English established the first eye bank there a few years later. Corneal transplantation evolved steadily over the twentieth century. In the second half of the century, developments in microsurgery, including surgical materials such as monofilament nylon and strong topical steroid drops, accounted for improvements in outcomes. In 2013, approximately 1500 corneal transplants were done in Australia. Eye banking has evolved to cope with the rising demands for donor corneas. Australian corneal surgeons collaborated to establish and support the Australian Corneal Graft Registry in 1985. It follows the outcomes of their surgery and has become an important international resource for surgeons seeking further improvement with the procedure. PMID- 25112898 TI - Current management of hemophilia B: recommendations, complications and emerging issues. AB - Hemophilia B is a rare hereditary hemorrhagic disorder characterized by deficiency of the clotting factor IX (FIX). Hemophilia B patients experience mild to-severe bleeding complications according to the degree of FIX defect. The mainstay of treatment of hemophilia B consists of replacement therapy and nowadays several plasma-derived and recombinant FIX products are commercially available. This article reviews the current management of hemophilia B patients analyzing the results of the most important clinical trials. In addition, it will focus on the more recent advances in the production of new FIX molecules aimed at the improvement of the clinical management of such patients. PMID- 25112896 TI - Sexual selection in true fruit flies (Diptera: Tephritidae): transcriptome and experimental evidences for phytochemicals increasing male competitive ability. AB - In male tephritid fruit flies of the genus Bactrocera, feeding on secondary plant compounds (sensu lato male lures = methyl eugenol, raspberry ketone and zingerone) increases male mating success. Ingested male lures alter the male pheromonal blend, normally making it more attractive to females and this is considered the primary mechanism for the enhanced mating success. However, the male lures raspberry ketone and zingerone are known, across a diverse range of other organisms, to be involved in increasing energy metabolism. If this also occurs in Bactrocera, then this may represent an additional benefit to males as courtship is metabolically expensive and lure feeding may increase a fly's short term energy. We tested this hypothesis by performing comparative RNA-seq analysis between zingerone-fed and unfed males of Bactrocera tryoni. We also carried out behavioural assays with zingerone- and cuelure-fed males to test whether they became more active. RNA-seq analysis revealed, in zingerone-fed flies, up regulation of 3183 genes with homologues transcripts to those known to regulate intermale aggression, pheromone synthesis, mating and accessory gland proteins, along with significant enrichment of several energy metabolic pathways and gene ontology terms. Behavioural assays show significant increases in locomotor activity, weight reduction and successful mating after mounting; all direct/indirect measures of increased activity. These results suggest that feeding on lures leads to complex physiological changes, which result in more competitive males. These results do not negate the pheromone effect, but do strongly suggest that the phytochemical-induced sexual selection is governed by both female preference and male competitive mechanisms. PMID- 25112899 TI - "It takes a village": multilevel approaches to recruit African Americans and their families for genetic research. AB - One barrier to searching for novel mutations in African American families with breast cancer is the challenge of effectively recruiting families-affected and non-affected relatives-into genetic research studies. Using a community-based participatory research (CBPR) orientation, we incorporated several evidence-based approaches through an iterative fashion to recruit for a breast cancer genetic epidemiology study in African Americans. Our combined methods allowed us to successfully recruit 341 African American women (247 with breast cancer and 94 relatives without breast cancer) from 127 families. Twenty-nine percent of participants were recruited through National Witness Project (NWP) sites, 11 % came from in-person encounters by NWP members, 34 % from the Love Army of Women, 24 % from previous epidemiologic studies, and 2 % from a support group. In terms of demographics, our varied recruitment methods/sources yielded samples of African American women that differ in terms of several sociodemographic factors such as education, smoking, and BMI, as well as family size. To successfully recruit African American families into epidemiological research, investigators should include community members in the recruitment processes, be flexible in the adoption of multipronged, iterative methods, and provide clear communication strategies about the underlying benefit to potential participants. Our results enhance our understanding of potential benefits and challenges associated with various recruitment methods. We offer a template for the design of future studies and suggest that generalizability may be better achieved by using multipronged approaches. PMID- 25112900 TI - Risk factors for mortality in patients with bloodstream infections caused by carbapenem-resistant Pseudomonas aeruginosa: clinical impact of bacterial virulence and strains on outcome. AB - The incidence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) bacteremia has increased in recent years, and infections caused by CRPA result in higher mortality than those caused by susceptible strains. This study was performed to evaluate the risk factors for mortality and to study the impact of virulence factors and bacterial strains on clinical outcomes in patients with CRPA bacteremia. Data on 63 episodes of CRPA bacteremia that have occurred between January 1, 2007, and December 31, 2009, in a teaching hospital (2000 beds) in Seoul, Korea, were analyzed. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the time of CRPA bacteremia and the capacity of CRPA to form biofilm were independent predictive factors for mortality in patients with CRPA bacteremia. In addition, the biofilm-forming ability and elastase activity of strains were correlated with APACHE II scores to measure the severity of disease and estimate predicted mortality in the patients. PMID- 25112901 TI - Real-time Leishmania genus master mix: a platform compatibility and stability study. AB - Performing diagnostics and vector-pathogen surveillance in austere environments is challenging. On-site diagnostic/detection mitigates vector-borne disease complications during military or humanitarian deployments to disease endemic locals. The mobile molecular diagnostic platform, Joint Biological Agent Identification and Diagnostic System (JBAIDS; BioFire Diagnostics Inc., Salt Lake City, UT, USA), rapidly identifies biothreat pathogens. Although ideal for remote diagnostics, the platform was validated for specific pathogens of insignificant epidemiological consequence. Recognizing the JBAIDS's remote diagnostic/detection versatility, we tested a Leishmania genus real-time PCR master mix validated for use on the SmartCycler(r) (Cepheid, Sunnyvale, CA, USA) for concomitant use on the JBAIDS. We evaluated assay sensitivity, precision, and specificity of one or more Leishmania spp. on the JBAIDS and found that the JBAIDS produces superior detection sensitivity and specificity compared to the SmartCycler(r). We also examined the storage stability of a bulk lot preparation of the Leishmania genus real-time PCR master mix on the SmartCycler(r) to ensure that long periods of frozen storage that would translate to a field environment with the JBAIDS were not detrimental to the reagent. We found that the bulk master mix maintains its stability over a 13-month time period. Overall, these studies confirm JBAIDS's versatility and demonstrate a streamlined assay development approach where reagents are compatible with both platforms. PMID- 25112903 TI - Polymorphism in NFKBIA gene is associated with recurrent acute rejections in liver transplant recipients. AB - The nuclear factor of kappa light polypeptide gene enhancer B-cells inhibitor alpha (NFKBIA) gene encodes a member of the nuclear factor-kappa-B inhibitor family. Polymorphisms in this gene might be associated with a susceptibility to acute rejection episodes following liver transplantation, as they may cause an increased activation level of the proinflammatory transcription factor nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFkappaB). The aim of this study was to evaluate whether the NFKBIA polymorphisms -297 C/T (rs2233409), -826 C/T (rs2233406) and 126 G/A (rs696) affect the incidence of acute liver graft rejection. A total of 199 liver transplant recipients was analyzed, 100 without (NAR) and 99 with early acute rejection (AR). Thirty-two individuals with multiple acute rejections (MAR) were analyzed as a subgroup of AR. Polymerase chain reaction-allele specific restriction enzyme analysis (PCR-ASRA) and allele specific hybridization with fluorescence resonance energy transfer (FRET) were used for genotyping. We identified the genotype NFKBIA 126 AA (P = 0.002) as well as the haplotype NFKBIA-126A-297T-826T (P = 0.002) as a potential risk factor for the occurrence of recurrent acute rejections. Furthermore, we assessed an association between the 126 A allele and susceptibility to recurrent acute rejections (P = 0.027). Our data suggest that the NFKBIA 126 G/A polymorphism might be potentially helpful to identify liver transplant recipients with an increased susceptibility to develop recurrent acute rejections. PMID- 25112902 TI - Carotid intima media thickness and other cardiovascular risk factors in children with congenital adrenal hyperplasia. AB - PURPOSE: Patients with congenital adrenal hyperplasia (CAH) are at increased risk for cardiovascular disease due to many factors. The aim of this study is to investigate the presence of dyslipidemia, insulin resistance, and subclinical atherosclerosis as indicated by carotid intima media thickness in children with congenital adrenal hyperplasia. METHODS: Thirty-two children with congenital adrenal hyperplasia (3-17 years) were compared with 32 healthy controls. All underwent anthropometric evaluation, measurement of fasting lipids, glucose, insulin, oral glucose tolerance test (OGTT), homeostasis model assessment for insulin resistance (HOMA-IR), and carotid intima media thickness (CIMT). RESULTS: Fasting glucose, glucose at 30, 60, 90, and 120 min during OGTT were significantly higher in patients. HOMA-IR was also significantly higher in patients (p = 0.036). Patients had significantly higher CIMT (p = 0.003), and higher systolic blood pressure. (p = 0.04). No significant difference existed in lipid profile. Both systolic and diastolic blood pressures correlated with treatment duration (p = 0.002, p = 0.043, respectively). CONCLUSION: Children with CAH are at increased risk of insulin resistance, glucose intolerance, early atherosclerosis, and cardiovascular disease. Screening of these patients at an early age is recommended. PMID- 25112905 TI - Canadian connective tissue society meeting schedule. PMID- 25112904 TI - Purification of Chitinase enzymes from Bacillus subtilis bacteria TV-125, investigation of kinetic properties and antifungal activity against Fusarium culmorum. AB - BACKGROUND: Chitin is the main structural component of cell walls of fungi, exoskeletons of insects and other arthropods and shells of crustaceans. Chitinase enzyme is capable of degrading chitin, and this enzyme can be used as a biological fungicide against phytopathogenic fungi, as well as an insecticide against insect pests. METHODS: In this study, 158 isolates, which were derived from bacteria cultures isolated from leaves and root rhizospheres of certain plants in Turkey, were selected after confirming that they are not phytopathogenic based on the hypersensitivity test performed on tobacco; and antifungal activity test was performed against Fusarium culmorum, which is a pathogenic fungi that cause decomposition of roots of vegetables. Accordingly, chitinase enzyme activity assay was performed on 31 isolates that have an antifungal activity, and among them the isolate of Bacillus subtilis TV-125 was selected, which has demonstrated the highest activity. RESULTS: Chitinase enzyme was purified by using ammonium sulphate and DEAE-sephadex ion exchange chromatography. Ammonium sulphate precipitation of chitinase enzyme from Bacillus subtilis TV-125 isolate was performed at maximum range of 0-20%, and 28.4-fold purification was obtained with a 13.4% of yield. Optimum activity of the purified enzyme was observed at pH 4.0 and at 50 degrees C of temperature. In addition, it was identified that Bacillus subtilis TV-125A isolate retains 42% of its activity at 80 degrees C temperature. CONCLUSION: In the last phase of the study, chitinase enzyme purified from Bacillus subtilis TV-125A was tested on four fungal agents, although all the results were positive, it was particularly effective on F. culmorum according to the findings. PMID- 25112906 TI - Reactions of atomic hydrogen with formic acid and carbon monoxide in solid parahydrogen I: Anomalous effect of temperature. AB - Low-temperature condensed phase reactions of atomic hydrogen with closed-shell molecules have been studied in rare gas matrices as a way to generate unstable chemical intermediates and to study tunneling-driven chemistry. Although parahydrogen (pH2) matrix isolation spectroscopy allows these reactions to be studied equally well, little is known about the analogous reactions conducted in a pH2 matrix host. In this study, we present Fourier transform infrared (FTIR) spectroscopic studies of the 193 nm photoinduced chemistry of formic acid (HCOOH) isolated in a pH2 matrix over the 1.7 to 4.3 K temperature range. Upon short-term irradiation the HCOOH readily undergoes photolysis to yield CO, CO2, HOCO, HCO and H atoms. Furthermore, after photolysis at 1.9 K tunneling reactions between migrating H atoms and trapped HCOOH and CO continue to produce HOCO and HCO, respectively. A series of postphotolysis kinetic experiments at 1.9 K with varying photolysis conditions and initial HCOOH concentrations show the growth of HOCO consistently follows single exponential (k = 4.9(7)x10(-3) min(-1)) growth kinetics. The HCO growth kinetics is more complex displaying single exponential growth under certain conditions, but also biexponential growth at elevated CO concentrations and longer photolysis exposures. By varying the temperature after photolysis, we show the H atom reaction kinetics qualitatively change at ~2.7 K; the reaction that produces HOCO stops at higher temperatures and is only observed at low temperature. We rationalize these results using a kinetic mechanism that involves formation of an H...HCOOH prereactive complex. This study clearly identifies anomalous temperature effects in the reaction kinetics of H atoms with HCOOH and CO in solid pH2 that deserve further study and await full quantitative theoretical modeling. PMID- 25112907 TI - Restoration of the interfacial properties of lung surfactant with a newly designed hydrocarbon/fluorocarbon lipid. AB - Serum proteins, especially fibrinogen, inactivate the lung surfactant mixture by adsorbing quickly and irreversibly to the alveolar air/aqueous interface. As a consequence of the inactivation, the surfactant becomes dysfunctional, and respiration cannot be maintained properly. Preventing the adsorption of surface active serum proteins to the air/water interface is important because this phenomenon causes fatal diseases such as acute respiratory distress syndrome (ARDS). Although some treatments exist, improvements in synthetic surfactants that can resist this inactivation are still expected. In this context, a novel ion pair lipid (IPL, CF3(CF2)7SO3(-)(CH2CH3)3N(+)(CH2OCH2)10(CH2)15CH3) has been designed and synthesized. This surfactant reduces the inhibitory effect of fibrinogen by selectively interacting with DPPC (dipalmitoylphosphatidylcholine) and mimicking some of the interfacial properties of the pulmonary surfactant protein B (SP-B). Surface pressure-area isotherms and fluorescence microscopy images demonstrate that IPL can mix and interact synergistically with DPPC due to its unique molecular structure. Hysteresis behaviors of the monolayers, which are composed of mixtures of DPPC and IPL at different molar ratios, indicate that with increasing amounts of IPL, the lipid losses from the interface induced by the presence of fibrinogen significantly decrease. It is also found that IPL is able to adsorb to monolayers formed in the presence of fibrinogen, whereas fibrinogen cannot penetrate the monolayers formed in the presence of IPL. These results indicate that by mimicking some of the interfacial properties of SP-B, this novel hybrid molecule is promising in terms of preventing fibrinogen adsorption and therefore resisting surfactant inactivation. PMID- 25112909 TI - Effect of hygroscopicity of the metal salt on the formation and air stability of lyotropic liquid crystalline mesophases in hydrated salt-surfactant systems. AB - It is known that alkali, transition metal and lanthanide salts can form lyotropic liquid crystalline (LLC) mesophases with non-ionic surfactants (such as CiH2i+1(OCH2CH2)jOH, denoted as CiEj). Here we combine several salt systems and show that the percent deliquescence relative humidity (%DRH) value of a salt is the determining parameter in the formation and stability of the mesophases and that the other parameters are secondary and less significant. Accordingly, salts can be divided into 3 categories: Type I salts (such as LiCl, LiBr, LiI, LiNO3, LiClO4, CaCl2, Ca(NO3)2, MgCl2, and some transition metal nitrates) have low %DRH and form stable salt-surfactant LLC mesophases in the presence of a small amount of water, type II salts (such as some sodium and potassium salts) that are moderately hygroscopic form disordered stable mesophases, and type III salts that have high %DRH values, do not form stable LLC mesophases and leach out salt crystals. To illustrate this effect, a large group of salts from alkali and alkaline earth metals were investigated using XRD, POM, FTIR, and Raman techniques. Among the different salts investigated in this study, the LiX (where X is Cl(-), Br(-), I(-), NO3(-), and ClO4(-)) and CaX2 (X is Cl(-), and NO3(-)) salts were more prone to establish LLC mesophases because of their lower %DRH values. The phase behavior with respect to concentration, stability, and thermal behavior of Li(I) systems were investigated further. It is seen that the phase transitions among different anions in the Li(I) systems follow the Hofmeister series. PMID- 25112908 TI - Relationships between molecular mobility, fibrillogenesis of collagen molecules, and the inflammatory response: an experimental study in vitro and in vivo. AB - This study was designed to investigate the in vitro adsorption and fibrillogenesis of collagen on a surface with dynamic properties and to investigate how this surface affected the inflammatory response in vivo. Investigation of collagen-surface interactions is directly related to the control of wound healing where collagen adsorption, fibrillization, deposition, and maturation occur. ABA-type block copolymers, composed of polyrotaxane (which possesses alpha-cyclodextrin threaded along poly(ethylene glycol)) and hydrophobic terminal segments, were used to prepare mobile surfaces with representative dynamic properties. Analyses using a quartz crystal microbalance with dissipation monitoring (QCM-D) indicated that increasing the mobility of the polymer on the surface led to the formation of a soft collagen layer. The collagens in this layer had rearranged, leading to the formation of thicker collagen fibrils by lateral aggregation. When a surface with a high molecular mobility was subcutaneously implanted into rats, collagen rearrangement occurred leading to suppression of macrophage recruitment at the interface and the formation of a fibrotic capsule around the implant. These results suggest that surface mobility on an implant is an important parameter for normal wound healing. PMID- 25112910 TI - Plasmonic response of DNA-assembled gold nanorods: effect of DNA linker length, temperature and linker/nanoparticles ratio. AB - Optical properties of gold nanorod (AuNR) particles self-assembled with DNA are systematically investigated. The particles assembly is driven by specific base pair recognition between single strand (ss) DNA linker and DNA anchored to AuNRs, and it results in the distance- and morphology-dependent plasmonic coupling of AuNRs. The longitudinal plasmon band is distinctly affected by tuning the length of DNA linker, the temperature and linker/AuNRs ratio. We observed that the increase of temperature enhances the interparticle interactions and leads to clear distinguishable plasmonic signals between linker lengths up to 100 bases. Both absorbance decrease and shift of the longitudinal plasmon allow for use of AuNR for the DNA sensing applications. PMID- 25112911 TI - Fabrication of mesoporous TiO2 membranes by a nanoparticle-modified polymeric sol process. AB - A straightforward synthesis of crack-free mesoporous titania membrane on a macroporous support without intermediate layers by a nanoparticle-modified polymeric sol-gel process is reported. TiO2 nanoparticle (Degussa P25) was dispersed into the prepared sol to toughen the formed gel. This helped to avoid the cracking of membrane during the drying and early stage of sintering, particularly when the sol-gel transformation occurred on a substrate with an uneven surface. The results of X-ray diffraction and Brunauer-Emmett-Teller analyses show that the nanoparticle doping did not significantly affect the particle size of TiO2 nanocrystals; however, it slightly broadened the pore size distribution because it has a larger particle size compared to the prepared materials. The sols with and without P25 nanoparticle were subsequently dip coated on a support with average pore size of 150nm, thus formed a mesoporous membrane layer after drying and sintering processes. An integrated, crack-free mesoporous TiO2 membrane layer was obtained by this method, while the membrane prepared with the original sol developed a few cracks. Further, the filtration experiment showed that the prepared membrane had a high flux, and the membrane with nanoparticle modification delivered better separation performance by rejection of dextran. PMID- 25112913 TI - Removal of oil from oil-in-saltwater emulsions by adsorption onto nano-alumina functionalized with petroleum vacuum residue. AB - Formation water from oilfields is one of the major environmental issues related to the oil industry. This research investigated oil adsorption onto nanoparticles of hydrophobic alumina and alumina nanoparticles functionalized with a petroleum vacuum residue (VR) at 2 and 4wt% to reduce the amount of oil in oil-saltwater emulsions at different pH values (5, 7 and 9). The initial concentration of crude oil in water ranged from 100 to 500mg/L. The change in oil concentration after adsorption was determined using a UV-vis spectrophotometer. The results indicated that all of the systems performed more effectively at a pH of 7 and using Al/4VR material. The oil adsorption was higher for neutral and acid systems compared with basic ones, and it was improved by increasing the amount of VR on the surface of the alumina. Additionally, the amount of NaCl adsorbed onto nanoparticles was estimated for different mixtures. The adsorption equilibrium and kinetics were evaluated using the Dubinin-Astakhov model, the Brunauer-Emmet Teller model, and pseudo-first- and pseudo-second-order models, with a better fitting to the Brunauer-Emmet-Teller model and pseudo-second-order model. PMID- 25112912 TI - Structural characterization and electrocatalytic application of hemoglobin immobilized in layered double hydroxides modified with hydroxyl functionalized ionic liquid. AB - Hemoglobin (Hb) was immobilized in Zn2Al-Layered Double Hydroxides (LDH) modified with Hydroxyl Functionalized Ionic Liquid (HFIL) through adsorption and coprecipitation method, respectively. Adsorption experiments showed that the presence of HFIL could enhance the maximum protein loading. However, the Hb loading through coprecipitation technique was far higher than that for adsorption. The role of HFIL on the interaction between Hb and LDH was investigated by XRD, FTIR, UV-vis and fluorescence spectroscopies. Although the quaternary structure of Hb entrapped in HFIL-LDH through coprecipitation technique (denoted as HFIL-LDH-Hbcop) might be altered slightly more than that in LDH (LDH-Hbcop), its secondary structure and redox-active heme groups kept intact. Morphologies of LDH-Hbcop and HFIL-LDH-Hbcop biohybrids were analyzed through SEM and TEM images. The direct electrochemistry of the immobilized Hb indicated that the coprecipitation bioelectrode performed better than that of the corresponding adsorption one. Regardless of adsorption and coprecipitation, the introduction of HFIL could distinctly promote the electron transport. Among all bioelectrodes, HFIL-LDH-Hbcop/GCE displayed the best electrocatalytic activity for H2O2 determination with a larger electroactive Hb percentage (6.76%), higher sensitivity (40.63A/Mcm(2)) and lower detection limit (0.0054MUmol/L). So HFIL LDH could effectively immobilize enzymes via coprecipitation technique, which had potential applications in the fabrication of electrochemical biosensors. PMID- 25112914 TI - Synthesis of magnetic core/shell carbon nanosphere supported manganese catalysts for oxidation of organics in water by peroxymonosulfate. AB - Magnetic separation is more cost-effective than conventional separation processes in heterogeneous catalysis, especially for ultrafine nanoparticles. Magnetic core/shell nanospheres (MCS, Fe3O4/carbon) were synthesized by a hydrothermal method and their supported manganese oxide nanoparticles (Mn/MCS) were obtained by redox reactions between MCS and potassium permanganate at a low temperature. The materials were analyzed by a variety of characterization techniques such as powder X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectrometer (EDS), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and N2 adsorption/desorption. The Mn/MCS catalysts were able to effectively activate Oxone(r) for phenol degradation in aqueous solutions. Nitrogen treated MCS supported Mn achieved 100% conversion within 120min. Kinetic studies showed that phenol degradation over supported Mn catalysts follows the first order kinetics. It was also found that the catalysts can be easily separated from the aqueous solutions by an external magnetic field. The Oxone(r) activation mechanism by Mn/MCS catalysts was discussed and sulfate radicals were suggested to be the primary reactive species generated from peroxymonosulfate (PMS) for phenol catalytic oxidation. PMID- 25112915 TI - Synthesis, characterization, and cellular uptake of magnetic nanocarriers for cancer drug delivery. AB - HYPOTHESIS: The absence of targetability is the primary inadequacy of conventional chemotherapy. Targeted drug delivery systems are conceptualized to overcome this challenge. We have designed a targetable magnetic nanocarrier consisting of a superparamagnetic iron oxide (SPIO) core and biocompatible and biodegradable poly(sebacic anhydride)-block-methyl ether poly(ethylene glycol) (PSA-mPEG) polymer shell. The idea is that this type of carriers should facilitate the targeting of cancer cells. EXPERIMENTS: PSA-mPEG was synthesized with poly-condensation and the in vitro degradation rate of the polymer was monitored by gel permeation chromatography (GPC). The magnetic nanocarriers were fabricated devoid of any surfactants and were capable of carrying high payload of hydrophobic dye. The successful encapsulation of SPIO within the polymer shell was confirmed by TEM. The results we obtained from measuring the size of SPIO loaded in polymeric NPs (SPIO-PNP) by dynamic light scattering (DLS) and iron content measurement of these particles by ICP-MS, indicate that SPIO is the most suitable carrier for cancer drug delivery applications. FINDINGS: Measuring the hydrodynamic radii of SPIO-PNPs by DLS over one month revealed the high stability of these particles at both body and room temperature. We further investigated the cell viability and cellular uptake of SPIO-PNPs in vitro with MDA-MB-231 breast cancer cells. We found that SPIO-PNPs induce negligible toxicity within a concentration range of 1-2MUg/ml. The TEM micrographs of thin cross-sectioned MDA MBA-231 cells showed internalization of SPIO-PNPs within size range of 150-200nm after 24h. This study has provided a foundation for eventually loading these nanoparticles with anti-cancer drugs for targeted cancer therapy using an external magnetic field. PMID- 25112916 TI - Self-assembly of flagellin on Au(111) surfaces. AB - The adsorption of flagellin monomers from Pseudomonas fluorescens on Au(111) has been studied by Atomic Force Microscopy (AFM), Scanning Tunneling Microscopy (STM), X-ray Photoelectron Spectroscopy (XPS), Surface Plasmon Resonance (SPR), and electrochemical techniques. Results show that flagellin monomers spontaneously self-assemble forming a monolayer thick protein film bounded to the Au surface by the more hydrophobic subunit and exposed to the environment the hydrophilic subunit. The films are conductive and allow allocation of electrochemically active cytochrome C. The self-assembled films could be used as biological platforms to build 3D complex molecular structures on planar metal surfaces and to functionalize metal nanoparticles. PMID- 25112918 TI - Ultrasensitive electrochemical biosensor for detection of DNA from Bacillus subtilis by coupling target-induced strand displacement and nicking endonuclease signal amplification. AB - A simple, ultrasensitive, and specific electrochemical biosensor was designed to determine the given DNA sequence of Bacillus subtilis by coupling target-induced strand displacement and nicking endonuclease signal amplification. The target DNA (TD, the DNA sequence from the hypervarient region of 16S rDNA of Bacillus subtilis) could be detected by the differential pulse voltammetry (DPV) in a range from 0.1 fM to 20 fM with the detection limit down to 0.08 fM at the 3s(blank) level. This electrochemical biosensor exhibits high distinction ability to single-base mismatch, double-bases mismatch, and noncomplementary DNA sequence, which may be expected to detect single-base mismatch and single nucleotide polymorphisms (SNPs). Moreover, the applicability of the designed biosensor for detecting the given DNA sequence from Bacillus subtilis was investigated. The result obtained by electrochemical method is approximately consistent with that by a real-time quantitative polymerase chain reaction detecting system (QPCR) with SYBR Green. PMID- 25112917 TI - Chars from gasification of coal and pine activated with K2CO3: acetaminophen and caffeine adsorption from aqueous solutions. AB - The high carbon contents and low toxicity levels of chars from coal and pine gasification provide an incentive to consider their use as precursors of porous carbons obtained by chemical activation with K2CO3. Given the chars characteristics, previous demineralization and thermal treatments were made, but no improvement on the solids properties was observed. The highest porosity development was obtained with the biomass derived char (Pi). This char sample produced porous materials with preparation yields near 50% along with high porosity development (ABET~1500m(2)g(-1)). For calcinations at 800 degrees C, the control of the experimental conditions allowed the preparation of samples with a micropore system formed almost exclusively by larger micropores. A mesopore network was developed only for samples calcined at 900 degrees C. Kinetic and equilibrium acetaminophen and caffeine adsorption data, showed that the processes obey to a pseudo-second order kinetic equation and to the Langmuir model, respectively. The results of sample Pi/1:3/800/2 outperformed those of the commercial carbons. Acetaminophen adsorption process was ruled by the micropore size distribution of the carbons. The caffeine monolayer capacities suggest a very efficient packing of this molecule in samples presenting monomodal micropore size distribution. The surface chemistry seems to be the determinant factor that controls the affinity of caffeine towards the carbons. PMID- 25112919 TI - HOMA-IR and the risk of hyperuricemia: a prospective study in non-diabetic Japanese men. AB - AIMS: To examine the relation of insulin resistant status determined by homeostasis model assessment of insulin resistance (HOMA-IR) with the risk of incident hyperuricemia. METHODS: The study participants included 2071 Japanese men without hyperuricemia and diabetes, aged 35-54 years. The participants had undergone annual heath examinations for 6 years to compare incident hyperuricemia (serum uric acid >416.4MUmol/L (7.0mg/dL) and/or taking medication for hyperuricemia) in four groups based on quartiles of baseline HOMA-IR. RESULTS: During follow-up there were 331 incident cases of hyperuricemia. The hazard ratios for hyperuricemia, compared with HOMA-IR <=0.66, were 1.42 (95% confidence interval 1.02-1.98) for HOMA-IR 0.67-0.98, 1.20 (0.86-1.68) for HOMA-IR 0.99-1.49 and 1.44 (1.04-1.98) for HOMA-IR >=1.50 after adjustment for baseline serum uric acid, creatinine, hypercholesterolemia and hypertension status, age, alcohol intake, and smoking and exercise habits. The hazard ratio associated with an increase of one standard deviation in lnHOMA-IR (1.85 as one geometric standard deviation of HOMA-IR) was 1.14 (1.03-1.28) (p for trend=0.02). CONCLUSIONS: Increased HOMA-IR independently predicted the subsequent development of hyperuricemia. Insulin resistance itself or compensatory hyperinsulinemia may contribute to the development of hyperuricemia. PMID- 25112920 TI - TRB3, up-regulated in kidneys of rats with type1 diabetes, mediates extracellular matrix accumulation in vivo and in vitro. AB - AIMS: Fibrosis is the final disorder of most chronic kidney disease including diabetic nephropathy (DN), but the mechanisms are not fully understood. The present study aims to determine whether TRB3 participates in fibrogenesis in DN. METHODS: Type1 diabetes was induced in male Wistar rats via intraperitoneal injection of streptozotocin (STZ). The expression of TRB3 and extracellular matrix (ECM) protein collagen I and fibronectin was investigated in kidneys of rats with diabetes and NRK-52E cells (a rat proximal tubular cell line) stimulated with albumin-overload. Rats without diabetes and NRK-52E cells without albumin stimulation served as control. Then gene silencing was used to study whether TRB3 participated in accumulation of collagen I and fibronectin in vivo and in vitro. RESULTS: TRB3 is up-regulated in renal tubules of kidneys of rats with diabetes, especially proximal tubules. Albumin-overload can augments TRB3 expression and increase collagen I and fibronectin secretion in NRK-52E cells. Importantly, silencing of TRB3 alleviates collagen I and fibronectin accumulation in kidneys of rats with diabetes and NRK-52E cells induced by albumin-overload. CONCLUSIONS: TRB3 mediates ECM accumulation in kidneys of rats with STZ-induced type1 diabetes and proximal tubular cells induced by albumin-overload, suggesting a potential target for treatment of DN. PMID- 25112922 TI - Instant coffee consumption may be associated with higher risk of metabolic syndrome in Korean adults. AB - AIMS: Cumulative evidence suggests that coffee consumption may have beneficial effects on metabolic diseases; however, few previous studies have considered the types of coffee consumed and the additives used. We investigated the relationship between coffee consumption and metabolic syndrome (MetSyn) and its components. METHODS: We analyzed 17,953 Korean adults, aged 19-65 years, using cross sectional data from the Korean National Health and Nutrition Examination Survey (KNHANES, 2007-2011). Coffee consumption level, types of coffee consumed, and the additives used were assessed based on a food frequency questionnaire and 24-h recall. Demographic and lifestyle factors were assessed using self-administered questionnaires. Data on metabolic biomarkers were obtained from a health examination. Multivariable logistic regression was used to determine the odds ratios of prevalent metabolic syndrome and its components according to frequency and type of coffee consumption. RESULTS: We found that 76% of the subjects were habitual coffee drinkers, most of whom consumed instant coffee mix containing sugar and powder creamer. After multivariable adjustment, the odds ratios (95% CI) comparing those who consumed coffee >=3 times/day with those who consumed coffee <1 time/week were 1.37 (1.15-1.63) for obesity, 1.33 (1.11-1.59) for abdominal obesity, 1.28 (1.09-1.51) for hypo-HDL cholesterolemia, and 1.37 (1.10 1.72) for metabolic syndrome. Instant-coffee drinkers were observed to have elevated risks of these metabolic conditions. CONCLUSIONS: Consumption of coffee, particularly instant coffee mix, may have harmful effects on MetSyn, perhaps partly deriving from excessive intake of sugar and powder creamer. PMID- 25112921 TI - Prevalence of diabetes and pre-diabetes among workers: Japan Epidemiology Collaboration on Occupational Health Study. AB - AIMS: Few studies have examined the prevalence of diabetes using glycated hemoglobin (HbA1c), a newly recommended diagnostic test. We examined the prevalence of diabetes and pre-diabetes using both HbA1c and fasting plasma glucose (FPG) and their associations with risk factors for type 2 diabetes in a large-scale Japanese working population. METHODS: Participants were 47,172 men and 8280 women aged 20-69 years who received periodic health checkup in nine companies which participated in the Japan Epidemiology Collaboration on Occupational Health study. Participants were categorized into diabetes (HbA1c>=6.5% (>=48mmol/mol), FPG>=126mg/dl (>=7.0mmol/L), or medication for diabetes), pre-diabetes (HbA1c 6.0-6.4% (42-46mmol/mol) or FPG 110-125mg/dl (6.1 6.9mmol/L) among those without diabetes), and normal glucose regulation. RESULTS: The prevalence of diabetes was 8.0% and 3.3% in men and women, respectively. Of individuals with diabetes, approximately 80% were defined by HbA1c>=6.5% (>=48mmol/mol) criterion. The prevalence of pre-diabetes was 14.1% in men and 9.2% in women. Prevalence of these glucose abnormalities increased with advancing age, especially during mid-40s and 50s. Higher body mass index and waist circumference, hypertension, dyslipidemia, and current smoking were each associated with higher prevalence of diabetes in both men and women. CONCLUSIONS: Using HbA1c and FPG criteria or current medication, one in 13 men and one in 30 women had diabetes in the present Japanese working population. Interventions targeted for those in an early stage of impaired glucose metabolism would be required to prevent diabetes. PMID- 25112923 TI - Illness beliefs predict self-care behaviours in patients with diabetic foot ulcers: a prospective study. AB - AIMS: Patients' illness beliefs are known to be influential determinants of self care behaviours in many chronic conditions. In a prospective observational study we examined their role in predicting foot self-care behaviours in patients with diabetic foot ulcers. METHODS: Patients (n=169) were recruited from outpatient podiatry clinics. Clinical and demographic factors, illness beliefs and foot self care behaviours were assessed as baseline (week 0). Foot self-care behaviours were assessed again 6, 12 and 24 weeks later. Linear regressions examined the contribution of beliefs at baseline to subsequent foot self-care behaviours, controlling for past behaviour (i.e., foot self-care at baseline) and clinical and demographic factors that may affect foot self-care (i.e., age and ulcer size). RESULTS: Our models accounted for between 42 and 58% of the variance in foot self-care behaviours. Even after controlling for past foot-care behaviours, age and ulcer size; patients' beliefs regarding the symptoms associated with ulceration, their understanding of ulceration and their perceived personal control over ulceration emerged as independent determinants of foot self-care. CONCLUSIONS: Patients' beliefs are important determinants of foot-care practices. They may, therefore, also be influential in determining ulcer outcomes. Interventions aimed at modifying illness beliefs may offer a means for promoting self-care and improving ulcer outcomes. PMID- 25112924 TI - The effect of six weeks endurance training on dynamic muscular control of the knee following fatiguing exercise. AB - The aim of the study was to examine whether six weeks of endurance training minimizes the effects of fatigue on postural control during dynamic postural perturbations. Eighteen healthy volunteers were assigned to either a 6-week progressive endurance training program on a cycle ergometer or a control group. At week 0 and 7, dynamic exercise was performed on an ergometer until exhaustion and immediately after, the anterior-posterior centre of pressure (COP) sway was analyzed during full body perturbations. Maximal voluntary contractions (MVC) of the knee flexors and extensors, muscle fiber conduction velocity (MFCV) of the vastus lateralis and medialis during sustained isometric knee extension contractions, and power output were measured. Following the training protocol, maximum knee extensor and flexor force and power output increased significantly for the training group with no changes observed for the control group. Moreover, the reduction of MFCV due to fatigue changed for the training group only (from 8.6% to 3.4%). At baseline, the fatiguing exercise induced an increase in the centre of pressure sway during the perturbations in both groups (>10%). The fatiguing protocol also impaired postural control in the control group when measured at week 7. However, for the training group, sway was not altered after the fatiguing exercise when assessed at week 7. In summary, six weeks of endurance training delayed the onset of muscle fatigue and improved the ability to control balance in response to postural perturbations in the presence of muscle fatigue. Results implicate that endurance training should be included in any injury prevention program. PMID- 25112925 TI - Mental health lived experience academics in tertiary education: the views of nurse academics. AB - BACKGROUND: Australian national mental health strategy emphasises inclusion of people diagnosed with mental illness in all areas of mental health care, policy development and education of health professionals. However, the way this inclusion has translated to Australian universities is relatively unexplored. OBJECTIVES: Explore views of nurse academics regarding service user involvement in nursing education programmes. DESIGN: Qualitative exploratory. SETTINGS: Australian universities offering educational programmes in nursing at postgraduate and undergraduate levels. PARTICIPANTS: Thirty four participants from 27 Australian universities participated. METHODS: Data were collected using semi-structured telephone interviews with academics involved in teaching and/or coordinating undergraduate and/or postgraduate mental health nursing contents. Data were analysed using content analysis based on four cognitive processes: comprehending, synthesising, theorising and re-contextualising data. RESULTS: Four major themes emerged: good idea? long way to go; conceptualising the service user academic role; strengths of lived experience led student learning; and barriers to implementation. CONCLUSIONS: Findings indicated strong support for including mental health service users in teaching nursing students. However, at most universities service user engagement was often an informal arrangement, lacking clear guidelines and limited by financial barriers and the positioning of mental health nursing within curricula. PMID- 25112926 TI - Does a volume reduction of the parietal lobe contribute to freezing of gait in Parkinson's disease? AB - BACKGROUND: Freezing of gait (FOG) is as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. Structural neuroimaging studies on FOG in PD using volumetric techniques yielded variable and partially conflicting findings, probably reflecting the heterogeneity and complexity of the phenomenon. The aim of this study was to further explore the differences in local gray matter (GM) volume in patients with PD with and without FOG by using Voxel-Based Morphometry (VBM). MATERIALS AND METHODS: We enrolled 26 patients (7 women and 19 men) with a diagnosis of PD in stable treatment with dopaminergic therapy. Thirteen patients classified as FOG+ were matched with thirteen non-freezer (FOG-) PD patients. All 26 participants underwent a detailed neuropsychological assessment as well as a VBM analysis derived from T1 weighted 3T MRI. RESULTS: The patient groups did not significantly differ for age, disease duration, H&Y stage, UPDRS part-III or educational attainment. No significant differences of cognitive profile emerged. PD-FOG+ patients showed a pattern of relative GM atrophy in left posterior parietal gyrus compared with PD-FOG-. DISCUSSION: Our results suggest that a specific pattern of cortical volume reduction involving posterior parietal cortex contributes to the occurrence of FOG in PD. These data agree with the growing body of evidence considering the parietal posterior cortex as an associative area involved in spatial control of motor behavior, par-taking in response selection to sensory evaluation. PMID- 25112927 TI - Wilate use in 47 children with von Willebrand disease: the North London paediatric haemophilia network experience. AB - Children with von Willebrand disease (VWD) in whom DDAVP is ineffective or contraindicated require treatment with a coagulation factor concentrate containing von Willebrand factor (VWF) and factor VIII (FVIII). The aim of this study was to monitor the safety, efficacy and tolerability of Wilate((r)) (a VWF:FVIII concentrate with a 1:1 ratio) used across the North London Paediatric Haemophilia Network since May 2010. In total, 47 children (aged 0.0-17.0 years) with type 1 (n = 28), type 2 (n = 7), type 3 (n = 10) and acquired VWS (n = 2) have been treated for bleeds, surgery and/or prophylaxis using 260 000 IU Wilate((r)). Analysis of dose and frequency of treatment show expected responses to treatment with mean doses of 55, 50 and 50 IU kg(-1) for bleeds, surgery and prophylaxis respectively. Most bleeds responded to a single treatment. Surgical procedures were covered with clinician approved dosing schedules with 95% (39/41) reported as having excellent or good efficacy. There was no accumulation of FVIII or VWF and no thromboembolic events. This case series confirms the efficacy, safety and tolerability of Wilate((r)) in neonates, children and adolescents when used on-demand, prophylactically and in the surgical setting. PMID- 25112928 TI - Propensity score-matched analysis of adjuvant chemotherapy for stage I non-small cell lung cancer. AB - OBJECTIVE: The aim of this study was to reevaluate the role of adjuvant chemotherapy for patients with stage I non-small cell lung cancer (NSCLC). METHODS: Data from 800 patients with completely resected pathologic stage I NSCLC who received adjuvant chemotherapy (n=191) and those who did not (n=609) were analyzed retrospectively and propensity score-matched pairs were determined. RESULTS: Although recurrence-free survival (RFS) and overall survival (OS) were not significantly different between patients who received adjuvant chemotherapy and those who did not in the univariate analyses, multivariate Cox analyses demonstrated that adjuvant chemotherapy was an independent prognostic factor for RFS and OS (P=.008 and P=.009, respectively). In 159 propensity score-matched pairs, including variables such as age, gender, smoking history, comorbidity, postoperative complication, histology, size of the invasive component of the tumor, and status of lymphatic, vascular, and pleural invasion, RFS and OS were considerably better in patients who received adjuvant chemotherapy (5-year RFS rate, 79.8%; 5-year OS rate, 89.3%) than in those who did not (5-year RFS rate, 60.2%; 5-year OS rate, 75.2%). Patients who received adjuvant chemotherapy showed significantly better RFS than those who did not in the group with an invasive component larger than 2 cm (5-year RFS rate, 74.4% vs 55.2%; P=.015) or in those with positive lymphatic invasion (5-year RFS rate, 63.3% vs 44.8%; P=.05). CONCLUSIONS: Adjuvant chemotherapy is effective for patients with stage I NSCLC, particularly those with an invasive component larger than 2 cm or those with lymphatic invasion. PMID- 25112929 TI - The impact of arterial cannulation strategy on operative outcomes in aortic surgery: evidence from a comprehensive meta-analysis of comparative studies on 4476 patients. AB - OBJECTIVES: There is a growing perception that peripheral cannulation through the femoral artery, by reversing the flow in the thoracoabdominal aorta, may increase the risk of retrograde brain embolization in aortic surgery. Central cannulation sites, including the right axillary artery, have been reported to improve operative outcomes by allowing antegrade blood flow. However, peripheral cannulation still remains largely used because a consensus for the routine use of central cannulation approaches has not been reached. METHODS: A meta-analysis of comparative studies reporting operative outcomes using central cannulation versus peripheral cannulation was performed. Pooled weighted incidence rates for end points of interest were obtained using an inverse variance model. RESULTS: A total of 4476 patients were included in the final analysis. Central cannulation was used in 2797 patients, and peripheral cannulation was used in 1679 patients. Central cannulation showed a protective effect on in-hospital mortality (risk ratio, 0.59; 95% confidence interval, 0.48-0.7; P < .001) and permanent neurologic deficit (risk ratio, 0.71; 95% confidence interval, 0.55-0.90; P = .005) when compared with peripheral cannulation. A trend toward an increased benefit in terms of reduced in-hospital mortality was observed when only the right axillary artery was used as the central cannulation approach (risk ratio, 0.35; 95% confidence interval, 0.22-0.55; P < .001; I(2) = 0%). CONCLUSIONS: Central cannulation was superior to peripheral cannulation in reducing in hospital mortality and the incidence of permanent neurologic deficit. This superiority was particularly evident when the axillary artery was used for central cannulation. PMID- 25112930 TI - Long-term results of aggressive hemiarch replacement in 534 patients with type A aortic dissection. AB - OBJECTIVE: To present the outcomes of routinely performed hemiarch replacement in patients with acute type A aortic dissection. METHODS: From 1993 to 2013, among 629 patients with acute type A dissection, 534 patients (85%) underwent hemiarch, 63 patients (10%) underwent hemiarch and antegrade thoracic stent grafting, 26 patients (4%) underwent total arch, and 6 patients (1%) underwent isolated ascending replacement. Patients with hemiarch replacement comprised the study population. Median follow-up was 4.1 years (first quartile, 1.9; third quartile, 7.8) (2462 patient years). RESULTS: In-hospital mortality was 12% (66 out of 534 patients). Survival was 80% +/- 2%, 68% +/- 3%, and 51% +/- 3%, and 84% +/- 3%, 65% +/- 4%, and 41% +/- 6% in DeBakey type I and II patients at 1, 5, and 10 years, respectively (log rank P = .375). Freedom from distal aortic reintervention was 97% +/- 1%, 90% +/- 2%, and 85% +/- 3% and 99% +/- 1%, 97% +/- 2%, and 90% +/- 5% in DeBakey type I and II patients at 1, 5, and 10 years, respectively (log rank P = .046). Seven patients (1.3%) required reintervention for aortic arch aneurysm and 25 patients (5%) required reintervention for descending aortopathy. The success rate for distal reintervention performed electively or urgently was 92% (24 out of 26 patients). Marfan syndrome (odds ratio, 3.43; P = .046) and DeBakey type I dissection (odds ratio, 2.49; P = .048) were independent predictors of distal aortic reintervention. CONCLUSIONS: Aggressive hemiarch replacement in acute type A dissection can be performed with low mortality and low aortic arch reoperation rate. Resection of all dissected aortic wall tissue decreases, but does not eliminate, the risk of later adverse aortic events. PMID- 25112932 TI - Synergistic protein secretion by mesenchymal stromal cells seeded in 3D scaffolds and circulating leukocytes in physiological flow. AB - Mesenchymal stromal cells (MSC) play an important role in natural wound healing via paracrine and juxtacrine signaling to immune cells. The aim of this study was to identify the signaling factors secreted by preseeded cells in a biomaterial and their interaction with circulating leukocytes, in the presence of physiological biomechanical stimuli exerted by the hemodynamic environment (i.e. strain and shear flow). Electrospun poly(epsilon-caprolactone)-based scaffolds were seeded with human peripheral blood mononuclear cells (PBMC) or MSC. Protein secretion was analyzed under static conditions and cyclic strain. Subsequently, the cross-talk between preseeded cells and circulating leukocytes was addressed by exposing the scaffolds to a suspension of PBMC in static transwells and in pulsatile flow. Our results revealed that PBMC exposed to the scaffold consistently secreted a cocktail of immunomodulatory proteins under all conditions tested. Preseeded MSC, on the other hand, secreted the trophic factors MCP-1, VEGF and bFGF. Furthermore, we observed a synergistic upregulation of CXCL12 gene expression and a synergistic increase in bFGF protein production by preseeded MSC exposed to PBMC in pulsatile flow. These findings identify CXCL12 and bFGF as valuable targets for the development of safe and effective acellular instructive grafts for application in in situ cardiovascular regenerative therapies. PMID- 25112931 TI - Phylogenetic analysis and evolutionary origins of DNA polymerase X-family members. AB - Mammalian DNA polymerase (pol) beta is the founding member of a large group of DNA polymerases now termed the X-family. DNA polymerase beta has been kinetically, structurally, and biologically well characterized and can serve as a phylogenetic reference. Accordingly, we have performed a phylogenetic analysis to understand the relationship between pol beta and other members of the X-family of DNA polymerases. The bacterial X-family DNA polymerases, Saccharomyces cerevisiae pol IV, and four mammalian X-family polymerases appear to be directly related. These enzymes originated from an ancient common ancestor characterized in two Bacillus species. Understanding distinct functions for each of the X-family polymerases, evolving from a common bacterial ancestor is of significant interest in light of the specialized roles of these enzymes in DNA metabolism. PMID- 25112933 TI - In vivo assessment of guided neural stem cell differentiation in growth factor immobilized chitosan-based hydrogel scaffolds. AB - In this study, we demonstrate that a unique growth factor-biomaterial system can offer spatial control of growth factors with sustained signaling to guide the specific lineage commitment of neural stem/progenitor cells (NSPCs) in vivo. First, recombinant fusion proteins incorporating an N-terminal biotin tag and interferon-gamma (IFN-gamma), platelet derived growth factor-AA (PDGF-AA), or bone morphogenic protein-2 (BMP-2) were immobilized to a methacrylamide chitosan (MAC) based biopolymer via a streptavidin linker to specify NSPC differentiation into neurons, oligodendrocytes, or astrocytes, respectively. MAC was mixed with growth factors (immobilized or adsorbed), acrylated laminin, NSPCs, and crosslinked within chitosan conduits. This system mimics regenerative aspects of the central nervous system ECM, which is largely composed of a crosslinked polysaccharide matrix with cell-adhesive regions, and adds the new functionality of protein sequestration. We demonstrated that these growth factors are maintained at functionally significant levels for 28 d in vitro. In the main study, immobilized treatments were compared to absorbed and control treatments after 28 d in vivo (rat subcutaneous). Masson's Trichrome staining revealed that small collagen capsules formed around the chitosan conduits with an average acceptable thickness of 153.07 +/- 6.02 MUm for all groups. ED-1 staining showed mild macrophage clustering around the outside of chitosan conduits in all treatments with no macrophage invasion into hydrogel portions. Importantly, NSPC differentiation staining demonstrated that immobilized growth factors induced the majority of cells to differentiate into the desired cell types as compared with adsorbed growth factor treatments and controls by day 28. Interestingly, immobilized IFN-gamma resulted in neural rosette-like arrangements and even structures resembling neural tubes, suggesting this treatment can lead to guided dedifferentiation and subsequent neurulation. PMID- 25112934 TI - X-ray CT guided fault-free photothermal ablation of metastatic lymph nodes with ultrafine HER-2 targeting W18O49 nanoparticles. AB - Designing high accuracy in the diagnosing and fault-freely eliminating lymphatic metastasis of breast malignancy, to avoid the invasiveness and complications caused by traditional assays, is of great therapeutic importance. To this end, theranostic W18O49 nanoparticles targeting to human epidermal growth receptor 2 (HER-2) over-expressed breast malignancy were synthesized via polyol method. By taking advantage of their high X-ray attenuating and photothermotherapy potency, lymph nodes in the mice bearing HER-2 positive metastasis could be clearly distinguished under CT guidance and selectively eliminated by laser ablation. The therapeutic efficacy was further confirmed by the significantly extended survival period. These finding evidenced the potential of these nanoparticles for imaging guided photothermal ablation of HER-2 positive breast malignancy. PMID- 25112936 TI - Tissue engineering of electrically responsive tissues using polyaniline based polymers: a review. AB - Conducting polymers have found numerous applications as biomaterial components serving to effectively deliver electrical signals from an external source to the seeded cells. Several cell types including cardiomyocytes, neurons, and osteoblasts respond to electrical signals by improving their functional outcomes. Although a wide variety of conducting polymers are available, polyaniline (PANI) has emerged as a popular choice due to its attractive properties such as ease of synthesis, tunable conductivity, environmental stability, and biocompatibility. PANI in its pure form has exhibited biocompatibility both in vitro and in vivo, and has been combined with a host of biodegradable polymers to form composites having a range of mechanical, electrical, and surface properties. Moreover, recent studies in literature report on the functionalization of polyaniline oligomers with end segments that make it biodegradable and improve its biocompatibility, two properties which make these materials highly desirable for applications in tissue engineering. This review will discuss the features and properties of PANI based composites that make them effective biomaterials, and it provides a comprehensive summary of studies where the use of PANI as a biomaterial component has enhanced cellular function and behavior. We also discuss recent studies utilizing functionalized PANI oligomers, and conclude that electroactive PANI and its derivatives show great promise in eliciting favorable responses from various cell lines that respond to electrical stimuli, and are therefore effective biomaterials for the engineering of electrically responsive biological tissues and organs. PMID- 25112935 TI - Multi-layered nanoparticles for combination gene and drug delivery to tumors. AB - Drug resistance and toxicity are major obstacles in cancer chemotherapy. Combination therapies can overcome resistance, and synergies can minimize dosing. Polymer nanocarriers are interesting vehicles for cancer therapeutics for their delivery and tumor targeting abilities. We synthesized a multi-layered polymer nanoparticle (MLNP), comprising of poly(lactic-co-glycolic acid) with surface polyethyleneimine and functional peptides, for targeted drug and gene delivery. We confirmed the particle's ability to inhibit tumor growth through synergistic action of the drug and gene product. MLNPs achieved transfection levels similar to lipofectamine, while maintaining minimal cytotoxicity. The particles delivered camptothecin (CPT), and plasmid encoding TNF related apoptosis inducing ligand (pTRAIL) (CT MLNPs), and synergistically inhibited growth of multiple cancer cells in vitro. The synergy of co-delivering CPT and pTRAIL via CT MLNPs was confirmed using the Chou-Talalay method: the combination index (CI) values at 50% inhibition ranged between 0.31 and 0.53 for all cell lines. Further, co-delivery with MLNPs resulted in a 3.1-15 fold reduction in CPT and 4.7-8.0 fold reduction in pTRAIL dosing. CT MLNPs obtained significant HCT116 growth inhibition in vivo compared to monotherapy. These results support our hypothesis that MLNPs can deliver both small molecules and genetic agents towards synergistically inhibiting tumor growth. PMID- 25112937 TI - In vitro and in vivo anti-biofilm effects of silver nanoparticles immobilized on titanium. AB - Prevention of periprosthetic infection (PPI) by inhibiting biofilm formation on prostheses is crucial to orthopedic surgery. In this work, silver nanoparticles (Ag NPs) are fabricated in situ and immobilized on titanium by silver plasma immersion ion implantation (PIII). The anti-biofilm activity rendered by the immobilized Ag NPs is assessed using Staphylococcus epidermidis, a biofilm producing strain, in vitro and in vivo. The immobilized Ag NPs show no apparent cytotoxicity but reduce biofilm formation in vitro by inhibiting bacteria adhesion and icaAD transcription. The immobilized Ag NPs offer a good defense against multiple cycles of bacteria attack in vitro, and the mechanism is independent of silver release. Radiographic assessment, microbiological cultures, and histopathological results demonstrate the ability of the functionalized surface against bacterial infection to reduce the risk of implant-associated PPI. PMID- 25112938 TI - Synergistic effect of amino acids modified on dendrimer surface in gene delivery. AB - Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery. PMID- 25112941 TI - Relationship between cervical sagittal alignment and quality of life in ankylosing spondylitis. AB - PURPOSE: Little information is available on the relationship between cervical sagittal alignment and health-related quality of life (HRQOL) in ankylosing spondylitis (AS) patients. The aim of this study was to identify relationships between cervical sagittal alignment and HRQOL in AS. METHODS: The study and control groups comprised 102 AS patients (15 women and 87 men) and age- and sex matched 50 controls, respectively. All underwent anteroposterior and lateral radiographs and completed clinical questionnaires. The radiographic parameters examined were C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), T1 slope and T1 slope minus C2-C7 lordosis (TS-CL). A visual analogue scale (VAS 0-10) score for neck pain, the neck disability index (NDI), neck pain and disability (NPAD) scale and bath ankylosing spondylitis disease activity index (BASDAI) were administered to evaluate QOL. Statistical analysis was performed to determine the significances of differences between the study and control groups. In addition, correlations between radiological parameters and clinical questionnaires were sought. RESULTS: AS patients and controls were found to be different significantly in terms of C2-C7 SVA, T1 slope, and TS-CL. However, no significant intergroup difference was observed for C2-C7 lordosis (P > 0.05). Correlation analysis revealed significant relationships between radiographic parameters and QOL. Multiple regression analysis was performed to identify predictors of QOL, and the results obtained revealed that C2-C7 SVA significantly predicted VAS, NDI, and NPAD scores and that age predicted NPAD score. CONCLUSIONS: Cervical sagittal parameters were found to be significantly different in AS patients and normal controls. Correlation analysis revealed significant relationships between radiographic parameters and QOL. In particular, C2-C7 SVA was found to be a significant predictor of QOL in AS patient. PMID- 25112942 TI - Atypical C2 fracture treated by posterior atlantoaxial fusion according to Goel/Harms. PMID- 25112943 TI - Functional connectivity in rat brain at 200 MUm resolution. AB - The somatosensory functional magnetic resonance imaging (fMRI) response to electrical stimulation of the middle phalange of the second digit of four rats at a spatial resolution of 200 MUm cubic at 9.4 T is reported. At high threshold (p<0.002), activated voxels encompass a penetrating vein that passes across the gray matter. These voxels lie mostly in three contiguous slices perpendicular to the pial surface. This activation is assigned to the representation in the forepaw barrel subfield (FBS) of a single cortical column of this phalange. In addition, the activation of the indusium griseum (IG) is visualized robustly. Voxels revealed by fMRI were used to observe functional connectivity to other voxels of the sensorimotor cortex using fcMRI. Results of this experiment were analyzed as a function of decreasing threshold, which exhibited spreading connectivity that revealed S2, M1/M2, and contralateral S1. Noting that every cubic millimeter of tissue contains 125 voxels, connectivity patterns are complex. It is hypothesized that they reflect connections within gray matter by association fibers. S2 and IG revealed connectivities with many voxels across the sensorimotor cortex. These regions also showed subregional variation of connectivity. A 1-cm-diameter surface coil with a local low-noise RF amplifier was used in these studies. The usual region of sensitivity (ROS) of such a coil is 1 cm diameter by 0.5 cm depth. Significant connectivity was observed between time courses of voxels that were within the ROS and voxels that were outside, which extends the volume of tissue that can be observed by the methods of this article. PMID- 25112944 TI - Client and key worker ratings of need in first-episode psychosis early intervention programmes. AB - AIM: The aim of this study was to fill a gap in the literature by examining agreement on need as rated by clients and their key workers from first-episode psychosis early intervention programmes. Compared with adult populations and more chronic courses of illness, these clients may have unique needs given the onset of their illness in adolescence or early adulthood. METHODS: Needs agreement between clients and key workers was assessed using the Camberwell Assessment of Need in a sample of 188 client-key worker pairs recruited from six early intervention programmes in Ontario, Canada. Ratings were assessed with percentage agreement and prevalence-adjusted Cohen's kappa. RESULTS: At the aggregate level, both clients and key workers rated a mean of 2.6 unmet needs. Compared with other diagnoses, key workers rated significantly more unmet need in clients with primary psychotic disorders. Agreement between individual client and key worker ratings was highest (adjusted kappa > 0.85) in the domains of telephone, risk to others, child care and accommodation. Lowest agreement (adjusted kappa < 0.4) was found in the domains of psychological distress, sexual expression, company, daytime activities and intimate relationships. CONCLUSIONS: While congruence is present in concrete domains, there is substantial variability in how clients and their key workers perceive need in more personal areas. The initial focus of care may necessarily be on needs such as shelter, food and treatment; however, subsequent care should incorporate a shared assessment of need to support strong relationships with providers and ongoing engagement in treatment. PMID- 25112945 TI - Vitamin B deficiencies in a critically ill autistic child with a restricted diet. AB - An 11-year-old male with autism became less responsive and was hospitalized with hepatomegaly and liver dysfunction, as well as severe lactic acidosis. His diet for several years was self-limited exclusively to a single "fast food"-a particular type of fried chicken-and was deficient in multiple micronutrients, including the B vitamins thiamine and pyridoxine. Lactic acidosis improved rapidly with thiamine; 2 weeks later, status epilepticus-with low serum pyridoxine-resolved rapidly with pyridoxine. Dietary B vitamin deficiencies complicated the care of this critically ill autistic child and should be considered in this setting. PMID- 25112946 TI - The personality of emergency nurses: is it unique? AB - BACKGROUND: With ever increasing demands on emergency services it is necessary to consider how to enhance the recruitment and retention of emergency nurses in public hospitals. Personality is known to influence occupational choice, yet there is a lack of research exploring how personality may influence the workforce decisions of emergency nurses. METHODS: A standardised personality test instrument, the NEOTM-PI-3, was used in a survey design inclusive of demographic questions to measure personality characteristics. Data were collected from 72 emergency nurses working at an Australian Emergency Department between July and October 2012. The personality scores of emergency nurses were compared against general population norms in each of five personality domains and their 30 associated facets. RESULTS: Participants scored higher than population norms in the domains of Extraversion (p < .001), Openness to experience (p < .001) and Agreeableness (p = .001), and in twelve facets, including excitement-seeking (p < .001) and competence (p = .003). CONCLUSION: The personality profile of this sample of emergency nurses is different to the population norm. Assessment of personality and knowledge of its influence on specialty selection may assist in improving retention and recruitment in emergency nursing. PMID- 25112947 TI - The emergency department prediction of disposition (EPOD) study. AB - BACKGROUND: Emergency departments (ED) continue to evolve models of care and streaming as interventions to tackle the effects of access block and overcrowding. Tertiary ED may be able to design patient-flow based on predicted dispositions in the department. Segregating discharge-stream patients may help develop patient-flows within the department, which is less affected by availability of beds in a hospital. We aim to determine if triage nurses and ED doctors can predict disposition outcomes early in the patient journey and thus lead to successful streaming of patients in the ED. METHODS: During this study, triage nurses and ED doctors anonymously predicted disposition outcomes for patients presenting to triage after their brief assessments. Patient disposition at the 24-h post ED presentation was considered as the actual outcome and compared against predicted outcomes. RESULTS: Triage nurses were able to predict actual discharges of 445 patients out of 490 patients with a positive predictive value (PPV) of 90.8% (95% CI 87.8-93.2%). ED registrars were able to predict actual discharges of 85 patients out of 93 patients with PPV of 91.4% (95% CI 83.3-95.9%). ED consultants were able to predict actual discharges of 111 patients out of 118 patients with PPV 94.1% (95% CI 87.7-97.4%). PPVs for admission among ED consultants, ED registrars and Triage nurses were 59.7%, 54.4% and 48.5% respectively. CONCLUSIONS: Triage nurses, ED consultants and ED registrars are able to predict a patient's discharge disposition at triage with high levels of confidence. Triage nurses, ED consultants, and ED registrars can predict patients who are likely to be admitted with equal ability. This data may be used to develop specific admission and discharge streams based on early decision-making in EDs by triage nurses, ED registrars or ED consultants. PMID- 25112950 TI - [Gender-specific aspects of coronary heart disease]. AB - The total number of deaths from cardiovascular diseases (CVD) is greater for women than for men, although the mean age at manifestation of CVD is about 10 years older. However, the annual number of cases treated for CVD in acute hospital settings in men exceeds that of women by 50 %. Remarkable gender differences exist in terms of morphological and physiological conditions (e.g. mean coronary vessel diameter; ability to adapt to protective exercise-induced myocardial hypertrophy), as well as of the frequency and clinical significance of somatic risk factors (e.g. smoking). Female body weight increases after menopause and the body shape assumes a more android fat distribution. Women report higher levels of unspecific and affective symptoms. They suffer more from anxiety and depression than men; however, the secondary impact on CVD onset may be less pronounced. The post-acute CVD course is more complicated in women, mainly because they are older and suffer more from multi-morbidity. Whilst male CVD patients aim for a rapid recovery, physical fitness and an increased life expectancy, female patients seek relief from everyday challenges, the maintenance of their independence and emotional support. PMID- 25112951 TI - [Health and gender]. PMID- 25112948 TI - Association of lifestyle habits and academic achievement in Norwegian adolescents: a cross-sectional study. AB - BACKGROUND: While healthy lifestyle habits are generally assumed to be important for high academic achievement, there has been little research on this topic among adolescents. The aim of this study was therefore to examine the associations between several lifestyle habits and academic achievement in adolescent girls and boys. METHODS: The study included 2,432 Norwegian adolescents, 15-17 years old. A self-report questionnaire was used to assess dietary-, physical activity-, smoking- and snuffing habits and academic achievement. Logistic regression models were adjusted for body mass index (BMI) and parental education. RESULTS: In both girls and boys, high academic achievement was associated with a regular consumption of breakfast (AOR: 3.30 (2.45-4.45) and AOR: 1.76 (1.32-2.34), respectively) and lunch (AOR: 1.44 (1.08-1.93) and AOR: 1.43 (1.09-1.89), respectively), and in boys, with a regular consumption of dinner (AOR: 1.44 (1.16 1.79)) and a regular meal pattern in general (AOR: 1.50 (1.10 - 2.03)). In both girls and boys, high academic achievement was associated with a high intake of fruit and berries (AOR: 2.09 (1.51-2.88) and AOR: 1.47 (1.04-2.07), respectively), and in girls, with a high intake of vegetables (AOR: 1.82 (1.30 2.53)). In both girls and boys, high academic achievement was associated with a high leisure time physical activity level (AOR: 1.51 (1.10-2.08) and AOR: 1.39 (1.05-1.85), respectively) and use of active commuting (AOR: 1.51 (1.10-2.08) and AOR: 1.72 (1.26-2.35), respectively). In both girls and boys, high academic achievement was associated with a low intake of lemonade (AOR: 0.42 (0.27-0.64) and AOR: 0.67 (0.48-0.94), respectively), and in girls, with a low intake of sugar-sweetened soft drinks (AOR: 0.47 (0.35- 0.64)) and salty snacks (AOR: 0.63 (0.47-0.85)). Lastly, high academic achievement was inversely associated with smoking and snuffing in both girls (AOR: 0.18 (0.12-0.25) and AOR: 0.25 (0.17 0.37), respectively) and boys (AOR: 0.37 (0.25-0.54) and AOR: 0.51 (0.36-0.72), respectively). CONCLUSIONS: A regular meal pattern, an intake of healthy food items and being physically active were all associated with increased odds of high academic achievement, whereas the intake of unhealthy food and beverages, smoking cigarettes and snuffing were associated with decreased odds of high academic achievement in Norwegian adolescents. PMID- 25112952 TI - [The EDQM Biological Standardisation Programme for the development of methods and reference preparations]. AB - The Biological Standardisation Programme (BSP) of the European Directorate for the Quality of Medicines & HealthCare (EDQM) was founded in 1992 with the objective to provide the necessary tools for the quality controls prescribed by the European Pharmacopoeia (Ph. Eur.). The BSP accomplishes this task by establishing reference standards and materials, as well as standardised control methods. A key aspect of BSP's work on development of methods is the validation of methods which can replace Ph. Eur. tests involving animals. The current area of work includes vaccines (for human and animal use), medicines produced from human plasma, hormones, cytokines, allergens, as well as reference materials and methods for determination of impurities and contaminations. BSP closely collaborates with the World Health Organization (WHO) and national authorities; many reference standards are established in joint projects with WHO. Participants of studies for establishing of reference materials and methods are mainly national control laboratories and manufacturers. BSP has to date run 131 projects, whereby 121 reference materials were established. Method development was the objective of 38 projects, with 21 thereof aiming at replacement of animal tests. BSP is funded by the EDQM (Council of Europe) and by the European Commission. With its activities BSP makes a significant contribution to quality, safety and efficacy of biological medicinal products in Europe and beyond, and serves thereby health and well-being of human beings and animals. PMID- 25112953 TI - 2'-Deoxyuridine conjugated with a reactive monobenzocyclooctyne as a DNA building block for copper-free click-type postsynthetic modification of DNA. AB - The carboxymethylmonobenzocyclooctyne group attached to the 5-position of a 2' deoxyuridine in DNA allows rapid and efficient copper-free postsynthetic modification as demonstrated with a far-red emitting fluorescent azide probe. Upon labeling strong fluorescence intensity enhancement is observed. PMID- 25112954 TI - Prevalence of macrolide, lincosamide, and streptogramin resistance among staphylococci in a tertiary care hospital in Athens, Greece. AB - The aims of the present study were to evaluate erythromycin, clindamycin, and streptogramin resistance rates, as well as the phenotypic and genotypic characteristics of erythromycin-resistant staphylococci in a Greek University Hospital. Macrolide, lincosamide, and streptogramin B-type resistance was investigated by double disk diffusion and the D-zone testing, while Minimal inhibitory concentration determination was performed among 656 erythromycin resistant staphylococcal clinical consecutive isolates, too. The presence of the major genetic determinants ermA, ermB, ermC, and msrA were detected by polymerase chain reaction (PCR). The overall erythromycin resistance rate was 49.70%. One hundred and forty-six of the 322 Staphylococcus aureus were methicillin-resistant S. aureus (MRSA) (45.34%), whereas 176 were methicillin-susceptible S. aureus (54.66%). The macrolides, lincosamides, and streptogramin B-type antibiotics (MLSB)-constitutive phenotype was detected in 126 S. aureus strains (88.7%), whereas the inducible MLSB resistance phenotype was demonstrated in 16 S. aureus (11.3%). The MS phenotype was not detected. ErmC was the most frequently encountered gene responsible for macrolide resistance among S. aureus and coagulase negative staphylococci in this hospital. Pulsed-field gel electrophoresis (PFGE) analysis of SmaI DNA fragments revealed the presence of a single predominant clone among erythromycin-resistant S. aureus. The predominance of constitutive erythromycin resistance is a serious problem and limits the use of clindamycin for severe staphylococcal infections not only in this university hospital, but in many countries worldwide. PMID- 25112955 TI - mecA-positive methicillin-sensitive Staphylococcus aureus clinical isolates in Zenica-Doboj Canton, Bosnia and Herzegovina. AB - Forty-four mecA-positive and eight mecA-negative Staphylococcus aureus isolates confirmed by PCR were further tested by disc-diffusion (DD) oxacillin and cefoxitin, oxacillin Epsilon (E)-test, and oxacillin and cefoxitin minimal inhibitory concentration (MIC) Strip methicillin-resistant phenotype in S. aureus (MRSA) tests. Among 44 mecA-positive S. aureus isolates, two (4.5%) were detected as MRSA by DD-oxacillin, 17 (38.6%) by DD-cefoxitin test, and seven (15.9%) by the E-test. In the cefoxitin MIC Strip MRSA test, 19 (43.2%) isolates were resistant. In the oxacillin MIC Strip MRSA test, 18 (40.9%) isolates were resistant and 26 (59.1%) were sensitive, i.e. oxacillin-sensitive MRSA (OS-MRSA) (MIC range 0.25-<=0.25 mg/l). Fifteen out of 26 OS-MRSA (57.7%) belonged to spa CC 355/595, 78% of which belonged to the largest PFGE clone. Some discrepancies between the phenotypic methods for MRSA identification obtained in this study were caused by large proportion of OS-MRSA. Misidentification of OS-MRSA as MSSA might result in an appearance of highly resistant MRSA in patients treated with beta-lactam antibiotics. PMID- 25112956 TI - Exome sequencing identifies frequent mutation of MLL2 in non-small cell lung carcinoma from Chinese patients. AB - Lung cancer is the most common cause of cancer mortality worldwide, with an estimated 1.4 million deaths each year. Here we report whole-exome sequencing of nine tumor/normal tissue pairs from Chinese patients with non-small cell lung carcinoma (NSCLC). This allows us to identify a number of significantly mutated genes in NSCLC, which were highly enriched in DNA damage repair, NF-kappaB pathway, JAK/STAT signaling and chromatin modification. Notably, we identify a histone-lysine methyltransferase gene, namely, MLL2, as one of the most significantly mutated genes in our screen. In a following validation study, we identify deleterious mutations of MLL2 in 12 out of 105 (11.4%) NSCLC patients. Additionally, reduced or lost expression of MLL2 was commonly observed in tumor tissues as compared with paired adjacent non-tumor tissues regardless of mutation status. Together, our study defines the landscape of somatic mutations in Chinese NSCLC and supports the role of MLL2 mutation in the pathogenesis of the disease. PMID- 25112957 TI - Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study. AB - INTRODUCTION: Since 2008, severe cases of emerging human adenovirus type 55 (HAdV 55) in immunocompetent adults have been reported sporadically in China. The clinical features and outcomes of the most critically ill patients with severe acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) are lacking. METHODS: We conducted a prospective, single-center observational study of pneumonia with ARDS in immunocompetent adults admitted to our respiratory ICU. We prospectively collected and analyzed clinical, laboratory, radiological characteristics, sequential tests of viral load in respiratory tract and blood, treatments and outcomes. RESULTS: The results for a total of five consecutive patients with severe ARDS with confirmed HAdV-55 infection were included. All five patients were immunocompetent young men with a median age of 32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas analysis at ICU admission revealed profound hypoxia. Mean partial oxygen pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a single-lobe consolidation shown on chest X-rays (CXRs) and, from the first positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days, respectively. The viral load was higher than 1 * 108 copies in three patients and was 1 * 104 in one patient. It was negative in the only patient who survived. The mean duration for noninvasive positive pressure ventilation (NPPV) failure and IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received venovenous ECMO. Four (80%) of the five patients died despite receiving appropriate respiratory support. CONCLUSIONS: HAdV-55 may cause severe ARDS in immunocompetent young men. Persistent high fever, dyspnea and rapid progression to respiratory failure within 2 weeks, together with bilateral consolidations and infiltrates, are the most frequent clinical manifestations of HAdV-55-induced severe ARDS. Viral load monitoring may help predict disease severity and outcome. The NPPV and IMV failure rates were very high, but ECMO may still be the respiratory support therapy of choice. TRIAL REGISTRATION: Clinicaltrials.gov NCT01585922. Registered 20 April 2012. PMID- 25112958 TI - Stereospecific hydrolysis of a phosphoramidate used as an OPIDP model by human sera with PON1 192 alloforms. AB - O-hexyl 2,5-dichlorophenyl phosphoramidate (HDCP) is a racemic organophosphate compound (OP) that induces delayed neuropathy in vivo. The O-hexyl 2,5 dichlorophenyl phosphoramidate R (R-HDCP) isomer inhibits and ages neuropathic target esterase (NTE) in hen brain. Moreover, human serum paraoxonase-1 (PON1) is a Ca(2+)-dependent enzyme capable of hydrolyzing OPs. The enzymatic activity of PON1 against OPs depends on the genetic polymorphisms present at position 192 (glutamine or arginine). The catalytic efficiency of PON1 is an important factor that determines neurotoxic susceptibility to some OPs. In the present study, we characterized the stereospecific hydrolysis of HDCP by alloforms PON1 Q192R human serum by chiral chromatography. Forty-seven human samples were characterized for the PON1 192 polymorphism. The hydrolysis data demonstrate that the three alloforms of PON1 show an exclusive and significant stereospecific Ca(2+) dependent hydrolysis of O-hexyl 2,5-dichlorophenyl phosphoramidate S isomer (S HDCP) at 19-127 uM at the concentrations that remain in all the samples. This stereoselective Ca(2+)-dependent hydrolysis of S-HDCP is inhibited by EDTA and is independent of the PON1 Q192R alloform. The present research reinforces the hypothesis that R-HDCP (an isomer that inhibits and causes NTE aging) is the enantiomer that induces delayed neuropathy by this chiral phosphoramidate due to the low hydrolysis level of the R-HDCP observed in this study. PMID- 25112959 TI - Re: Waalkes et al.: Lung tumors in mice induced by "whole-life" inorganic arsenic exposure at human-relevant doses, Arch Toxicol, 2014. PMID- 25112960 TI - Evaluation of apically extruded debris associated with several Ni-Ti systems. AB - AIM: To evaluate the apical extrusion of debris associated with several root canal preparation systems in vitro. METHODOLOGY: Forty-five extracted human mandibular premolars with single canals and similar lengths were used. The root canals were instrumented using ProTaper Next (Dentsply Maillefer, Ballaigues, Switzerland), Twisted File (SybronEndo, Orange, CA, USA) or WaveOne (Dentsply Maillefer, Ballaigues, Switzerland). Debris extruded apically during instrumentation was collected into pre-weighed Eppendorf tubes. The Eppendorf tubes were then stored in an incubator at 70 degrees C for 5 days. The Eppendorf tubes were weighed to obtain the final weight of the Eppendorf tubes plus extruded debris. Three consecutive weights were obtained for each tube. The groups were compared using the Kruskal-Wallis one-way analysis of variance on Ranks and Tukey's test. RESULTS: The ProTaper Next group produced the highest mean extrusion value whilst WaveOne produced less debris compared with all the other instruments (P > 0.05). There was a significant difference between the ProTaper Next and WaveOne group (P < 0.05). CONCLUSIONS: Apically extruded debris was associated with all instrumentation techniques. The WaveOne system extruded less debris compared with the Twisted File and ProTaper Next. PMID- 25112962 TI - The resemblance and disparity of gene expression in dormant and non-dormant seeds and crown buds of leafy spurge (Euphorbia esula). AB - BACKGROUND: Leafy spurge (Euphorbia esula L.) is a herbaceous perennial weed and dormancy in both buds and seeds is an important survival mechanism. Bud dormancy in leafy spurge exhibits three well-defined phases of para-, endo- and ecodormancy; however, seed dormancy for leafy spurge is classified as physiological dormancy that requires after-ripening and alternating temperature for maximal germination. Overlaps in transcriptome profiles between different phases of bud and seed dormancy have not been determined. Thus, we compared various phases of dormancy between seeds and buds to identify common genes and molecular processes, which should provide new insights about common regulators of dormancy. RESULTS: Cluster analysis of expression profiles for 201 selected genes indicated bud and seed samples clustered separately. Direct comparisons between buds and seeds are additionally complicated since seeds incubated at a constant temperature of 20 degrees C for 21 days (21d C) could be considered paradormant (Para) because seeds may be inhibited by endosperm-generated signals, or ecodormant (Eco) because seeds germinate after being subjected to alternating temperature of 20:30 degrees C. Since direct comparisons in gene expression between buds and seeds were problematic, we instead examined commonalities in differentially-expressed genes associated with different phases of dormancy. Comparison between buds and seeds ('Para to Endo buds' and '21d C to 1d C seeds'), using endodormant buds (Endo) and dormant seeds (1d C) as common baselines, identified transcripts associated with cell cycle (HisH4), stress response/transcription factors (ICE2, ERFB4/ABR1), ABA and auxin response (ABA1, ARF1, IAA7, TFL1), carbohydrate/protein degradation (GAPDH_1), and transport (ABCB2). Comparison of transcript abundance for the 'Eco to Endo buds' and '21d C to 1d C seeds' identified transcripts associated with ABA response (ATEM6), auxin response (ARF1), and cell cycle (HisH4). These results indicate that the physiological state of 21d C seeds is more analogous to paradormant buds than that of ecodormant buds. CONCLUSION: Combined results indicate that common molecular mechanisms associated with dormancy transitions of buds and seeds involve processes associated with ABA and auxin signaling and transport, cell cycle, and AP2/ERF transcription factors or their up-stream regulators. PMID- 25112965 TI - Doping of wide-bandgap titanium-dioxide nanotubes: optical, electronic and magnetic properties. AB - Doping semiconductors is an important step for their technological application. While doping bulk semiconductors can be easily achieved, incorporating dopants in semiconductor nanostructures has proven difficult. Here, we report a facile synthesis method for doping titanium-dioxide (TiO2) nanotubes that was enabled by a new electrochemical cell design. A variety of optical, electronic and magnetic dopants were incorporated into the hollow nanotubes, and from detailed studies it is shown that the doping level can be easily tuned from low to heavily-doped semiconductors. Using desired dopants - electronic (p- or n-doped), optical (ultraviolet bandgap to infrared absorption in co-doped nanotubes), and magnetic (from paramagnetic to ferromagnetic) properties can be tailored, and these technologically important nanotubes can be useful for a variety of applications in photovoltaics, display technologies, photocatalysis, and spintronic applications. PMID- 25112961 TI - Next-generation endomyocardial biopsy: the potential of confocal and super resolution microscopy. AB - Confocal laser scanning microscopy and super-resolution microscopy provide high contrast and high-resolution fluorescent imaging, which has great potential to increase the diagnostic yield of endomyocardial biopsy (EMB). EMB is currently the gold standard for identification of cardiac allograft rejection, myocarditis, and infiltrative and storage diseases. However, standard analysis is dominated by low-contrast bright-field light and electron microscopy (EM); this lack of contrast makes quantification of pathological features difficult. For example, assessment of cardiac allograft rejection relies on subjective grading of H&E histology, which may lead to diagnostic variability between pathologists. This issue could be solved by utilising the high contrast provided by fluorescence methods such as confocal to quantitatively assess the degree of lymphocytic infiltrate. For infiltrative diseases such as amyloidosis, the nanometre resolution provided by EM can be diagnostic in identifying disease-causing fibrils. The recent advent of super-resolution imaging, particularly direct stochastic optical reconstruction microscopy (dSTORM), provides high-contrast imaging at resolution approaching that of EM. Moreover, dSTORM utilises conventional fluorescence dyes allowing for the same structures to be routinely imaged at the cellular scale and then at the nanoscale. The key benefit of these technologies is that the high contrast facilitates quantitative digital analysis and thereby provides a means to robustly assess critical pathological features. Ultimately, this technology has the ability to provide greater accuracy and precision to EMB assessment, which could result in better outcomes for patients. PMID- 25112963 TI - Expression of the long-chain fatty acid receptor GPR120 in the gonadotropes of the mouse anterior pituitary gland. AB - G-protein-coupled receptor 120 (GPR120) has been known to be a receptor of long chain fatty acids. Here, we investigated GPR120 expression in the mouse pituitary gland via real-time PCR, in situ hybridization, and immunohistochemistry. GPR120 mRNA was abundantly expressed in the pituitary gland of ad-lib fed animals. In situ hybridization and immunohistochemistry revealed GPR120 expression in the gonadotropes of the anterior pituitary gland, but not in thyrotropes, somatotropes, lactotropes, corticotropes, melanotropes, and the posterior pituitary gland. Furthermore, 24 h of fasting induced an increase in GPR120 mRNA expression in the pituitary gland. These results demonstrate that GPR120 in mouse pituitary gonadotropes is upregulated by fasting and that it may play a role in controlling gonadotropin secretion. PMID- 25112966 TI - Wheelchair appropriateness in patients with spinal cord injury: a Turkish experience. AB - STUDY DESIGN: Descriptive. OBJECTIVE: To determine the wheelchair appropriateness in patients with spinal cord injury (SCI). SETTING: National Rehabilitation Center in Ankara, Turkey. METHODS: Twenty-seven (25 male, 2 female) SCI patients were included. Demographic and clinical characteristics of the patients were noted. All wheelchairs were evaluated considering each part (seat length, seat depth, seat height, back height, armrest, headrest, wheels and seat belt) by a physiatrist who had attended the wheelchair-training course. The wheelchair was declared as inappropriate if at least three parts of wheelchair were not appropriate. RESULTS: The mean age of the patients was 32.9+/-9.3 years and mean duration of wheelchair use was 19.63+/-23.02 months. Among the patients, 21 (77.8%) were American Spinal Injury Association Impairment Scale (AIS) A, 4 (3.7%) AIS B, 1 (3.7%) AIS C and 1 (3.7%) AIS D. Five (18.5%) wheelchairs were motorized and 22 (81.5%) were manual. Overall, 15 (55.6%) wheelchairs were inappropriate. Seat height, cushion and back height were the most common inappropriate parts. CONCLUSION: In light of our first and preliminary results, we can argue that 55% of the patients with SCI use inappropriate wheelchairs. In order to achieve better mobility; personally designed wheelchairs should be prescribed by the clinicians. PMID- 25112967 TI - Association of acute pancreatitis or high level of serum pancreatic enzymes in patients with acute spinal cord injury: a prospective study. AB - BACKGROUND: Spinal cord injuries has increased together with urban violence and show a high rates of incidence. Besides the onus to patient and society, it can also cause other serious complications to victims. Acute pancreatitis has an important impact on this disease and has been underdiagnosed in several patients. OBJECTIVES: The aim of this study was investigate the association of acute pancreatitis in acute spinal cord injuries. The secondary aim was to propose an investigation protocol to early diagnose and prevent it. METHODS: A prospective observational study was conducted in 78 patients who presented acute spinal cord injury (SCI) at our emergency department, confirmed by clinical and imaging examination, in according to the American Spinal Injury Association (ASIA) Classification. Exclusion criteria were chronic or associate diseases in spinal cord, pancreatic direct trauma, alcoholism and chronic pancreatic disease. RESULTS: The association of acute pancreatitis in patients with SCI was 11.53%. The occurrence of pancreatitis or high levels of serum pancreatic enzymes in patients with ASIA A was 41.7% and only 4.17% in patients with ASIA E. In all, 55.2% of patients who presented pancreatitis or high levels of serum pancreatic enzymes had cervical level of SCI and 34.5% had thoracic level. Adynamic ileus was observed in 68.96% of this group. CONCLUSION: We concluded that, in acute spinal cord injuries, the occurrence of acute pancreatitis or high serum levels of pancreatic enzymes are more frequent in patients with ASIA A Classification, cervical/thoracic level of spinal injury and adynamic ileus. PMID- 25112968 TI - Centralized spinal cord injury care in Finland: unveiling the hidden incidence of traumatic injuries. AB - STUDY DESIGN: Population-based prospective study. OBJECTIVES: To determine the incidence and evaluate the characteristics of newly injured patients with traumatic spinal cord injury (TSCI) admitted to two of the three national spinal cord injury (SCI) centers during the first year after the centralization of SCI care in Finland. SETTING: Oulu and Tampere University Hospital SCI centers, Finland. METHODS: The designated rehabilitation teams evaluated all of the patients with a new SCI and persisting neurological symptoms. The data were recorded according to the International Spinal Cord Injury Core Data Set. RESULTS: In a 1-year period, 77 new patients with TSCI were admitted to the study centers serving a population of 3 065 946. In the whole catchment area, the mean annual incidence of TSCI was 25.1 per million, and in the hospital districts of the SCI centers, the incidence was even higher, at 38.1 per million. The mean age of the patients was 58.7 years. Falls were the leading cause of injury (64.9%), and the injury resulted in tetraplegia in 70.1% of the cases. Alcohol use was a contributing factor in 39% of the cases in the entire sample and in 58.6% of cases among patients aged younger than 60 years. CONCLUSION: The incidence rates of TSCI were markedly higher than expected, demonstrating the previously hidden morbidity. The epidemiological features of TSCI appeared to follow the trends in developed countries, highlighting the increasing incidence of cervical lesions due to falling among the elderly. The results need to be confirmed in an extended follow-up. PMID- 25112969 TI - Intermittent catheterization in patients with traumatic spinal cord injury: obstacles, worries, level of satisfaction. AB - OBJECTIVES: The aim of this study is to examine the obstacles in people with traumatic spinal cord injury (SCI) face performing intermittent catheterization (IC), also their worries and level of satisfaction. METHODS: Two hundred sixty nine patients performing IC for at least 3 months were asked to fill-out a questionnaire about their opinions on IC. RESULTS: In total, 69.5% of patients performed IC themselves, 10.4% had performed by their mothers, 7.8% by another caregiver and 7.4% by their spouse. For the 72 (26%) patients unable to apply IC, reasons were insufficient hand function (56.1%), being unable to sit appropriately (35.4%) and spasticity (8.5%). In all, 70% of male patients had insufficient hand function, 20% could not sit and 10% had spasticity while 56.3% of female patients could not sit, 37.5% had insufficient hand function and 63% had spasticity. Difference between sexes was found to be statistically significant (P<0.05). Worries patients had when starting IC were fear of being dependent on IC (50.2%), accidentally injuring self (43.8%), embarrassment (43.2%), causing an infection (40.2%), bleeding (32.7%), fear of feeling pain (30.2%) and hygiene (24.7%). More women felt embarrassment; other items were similar in both sexes. In all, 46.9% of patients had urinary incontinence in intervals. CONCLUSION: In total, 69.5% of patients performed IC themselves. Men's most common obstacle was insufficient hand function while women's was being unable to sit appropriately. Patients' most common worries were being dependent on IC for life. In all, 46.9% had incontinence in intervals; 47.9% said IC improved their life quality; and 97.4% preferred IC over continuous catheterization. PMID- 25112970 TI - rTMS modulates reciprocal inhibition in patients with traumatic spinal cord injury. AB - STUDY DESIGN: Randomized, double-blind, crossover, sham-controlled trial. OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) leads to a significant reduction of spasticity in subjects with spinal cord injury (SCI), but the physiological basis of this effect is still not well understood. The purpose of this study was to evaluate the disynaptic reciprocal Ia inhibition of soleus motoneurons in SCI patients. SETTING: Department of Neurology, Merano, Italy and TMS Laboratory, Paracelsus Medical University, Salzburg, Austria. METHODS: Nine subjects with incomplete cervical or thoracic SCI received 5 days of daily sessions of real or sham rTMS applied over the contralateral M1. We compared the reciprocal inhibition, the Modified Ashworth Scale and the Spinal Cord Injury Assessment Tool for Spasticity at baseline, after the last session and 1 week later in the real rTMS and sham stimulation groups. RESULTS: We found that real rTMS significantly reduced lower limb spasticity and restored the impaired excitability in the disynaptic reciprocal inhibitory pathway. CONCLUSIONS: In a small proof-of-concept study, rTMS strengthened descending projections between the motor cortex and inhibitory spinal interneuronal circuits. This reversed a defect in reciprocal inhibition after SCI, and reduced leg spasticity. PMID- 25112971 TI - Thioetherification of chloroheteroarenes: a binuclear catalyst promotes wide scope and high functional-group tolerance. AB - A constrained binuclear palladium catalyst system affords selective thioetherification of a wide range of functionalized arenethiols with chloroheteroaromatic partners with the highest turnover numbers (TONs) reported to date and tolerates a large variety of reactive functions. The scope of this system includes the coupling of thiophenols with six- and five-membered 2 chloroheteroarenes (i.e., functionalized pyridine, pyrazine, quinoline, pyrimidine, furane, and thiazole) and 3-bromoheteroarenes (i.e., pyridine and furane). Electron-rich congested thiophenols and fluorinated thiophenols are also suitable partners. The coupling of unprotected amino-2-chloropyridines with thiophenol and the successful employment of synthetically valuable chlorothiophenols are described with the same catalyst system. DFT studies attribute the high performance of this binuclear palladium catalyst to the decreased stability of thiolate-containing resting states. Palladium loading was as low as 0.2 mol %, which is important for industrial application and is a step forward in solving catalyst activation/deactivation problems. PMID- 25112972 TI - Calibrating corneal material model parameters using only inflation data: an ill posed problem. AB - Goldmann applanation tonometry (GAT) is a method used to estimate the intraocular pressure by measuring the indentation resistance of the cornea. A popular approach to investigate the sensitivity of GAT results to material and geometry variations is to perform numerical modelling using the finite element method, for which a calibrated material model is required. These material models are typically calibrated using experimental inflation data by solving an inverse problem. In the inverse problem, the underlying material constitutive behaviour is inferred from the measured macroscopic response (chamber pressure versus apical displacement). In this study, a biomechanically motivated elastic fibre reinforced corneal material model is chosen. The inverse problem of calibrating the corneal material model parameters using only experimental inflation data is demonstrated to be ill-posed, with small variations in the experimental data leading to large differences in the calibrated model parameters. This can result in different groups of researchers, calibrating their material model with the same inflation test data, drawing vastly different conclusions about the effect of material parameters on GAT results. It is further demonstrated that multiple loading scenarios, such as inflation as well as bending, would be required to reliably calibrate such a corneal material model. PMID- 25112973 TI - Melatonin promotes seed germination under high salinity by regulating antioxidant systems, ABA and GA4 interaction in cucumber (Cucumis sativus L.). AB - Although previous studies have found that melatonin can promote seed germination, the mechanisms involved in perceiving and signaling melatonin remain poorly understood. In this study, it was found that melatonin was synthesized during cucumber seed germination with a peak in melatonin levels occurring 14 hr into germination. This is indicative of a correlation between melatonin synthesis and seed germination. Meanwhile, seeds pretreated with exogenous melatonin (1 MUM) showed enhanced germination rates under 150 mM NaCl stress compared to water pretreated seeds under salinity stress. There are two apparent mechanisms by which melatonin alleviated salinity-induced inhibition of seed germination. Exogenous melatonin decreased oxidative damage induced by NaCl stress by enhancing gene expression of antioxidants. Under NaCl stress, compared to untreated control, the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) were significantly increased by approximately 1.3-5.0-fold, with a concomitant 1.4-2.0-fold increase of CsCu-ZnSOD, CsFe-ZnSOD, CsCAT, and CsPOD in melatonin-pretreated seeds. Melatonin also alleviated salinity stress by affecting abscisic acid (ABA) and gibberellin acid (GA) biosynthesis and catabolism during seed germination. Compared to NaCl treatment, melatonin significantly up-regulated ABA catabolism genes (e.g., CsCYP707A1 and CsCYP707A2, 3.5 and 105-fold higher than NaCl treatment at 16 hr, respectively) and down-regulated ABA biosynthesis genes (e.g., CsNECD2, 0.29-fold of CK2 at 16 hr), resulting in a rapid decrease of ABA content during the early stage of germination. At the same time, melatonin positively up-regulated GA biosynthesis genes (e.g., GA20ox and GA3ox, 2.3 and 3.9-fold higher than NaCl treatment at 0 and 12 hr, respectively), contributing to a significant increase of GA (especially GA4) content. In this study, we provide new evidence suggesting that melatonin alleviates the inhibitory effects of NaCl stress on germination mainly by regulating the biosynthesis and catabolism of ABA and GA4. PMID- 25112974 TI - Epidemiology of Wilson's disease in Ireland. PMID- 25112976 TI - Revisionary checklist of the Southern African Sesiini (Lepidoptera: Sesiidae) with description of new species. AB - A revisionary checklist of the Sesiini of southern Africa is presented. All known genera of the region and their type species are redescribed. The following genera are placed in Sesiini for the first time: Alonina Walker, 1856; Anaudia Wallengren, 1863; Austrosetia Felder & Felder, 1874; Megalosphecia Le Cerf, 1916 and Vespanthedon Le Cerf, 1917. The genera Cicinnoscelis Holland, 1893 rev. stat. (from synonymy with Alonina Walker, 1856) and Felderiola Naumann, 1971 rev. stat. (from synonymy with Monopetalotaxis Wallengren, 1859) are resurrected from synonymy and included in Sesiini. One new genus, Hagnogyna new gen., and seven new species, Cicinnoscelis flavipes new sp., C. krooni new sp., Alonina rufa new sp., A. fusca new sp., Anaudia thyranthrena new sp., Felderiola karooensis new sp. and F. xanthogaster new sp., are described. The following new combinations are introduced: Cicinnoscelis longipes Holland, 1893 rev. comb., Alonina pyrethra (Hampson, 1919) new comb., A. pyrocraspis (Hampson, 1910) new comb., A. luteopunctata (Freina, 2011) new comb., Felderiola candescens (Felder & Felder, 1874) rev. comb., Hagnogyna sanguicosta (Hampson, 1919) new comb., H. bartschi (Freina, 2011) new comb. and Vespanthedon chalciphora (Hampson, 1919) new comb. Alonina difformis Hampson, 1919 new syn. is considered a subjective junior synonym of A. rygchiiformis Walker, 1856. A lectotype is designated for Austrosetia semirufa Felder & Felder, 1874 and the previously unknown males of this species and of Anaudia felderi Wallengren, 1863 are described. Bionomical data for some of the species discussed are given for the first time. PMID- 25112975 TI - Epigenetic promoter silencing in Friedreich ataxia is dependent on repeat length. AB - OBJECTIVE: Friedreich ataxia (FRDA) is caused by an expanded GAA triplet-repeat (GAA-TR) mutation in the FXN gene. Patients are typically homozygous for expanded alleles containing 100 to 1,300 triplets, and phenotypic severity is significantly correlated with the length of the shorter of the 2 expanded alleles. Patients have a severe deficiency of FXN transcript, which is predominantly caused by epigenetic silencing of the FXN promoter. We sought to determine whether the severity of FXN promoter silencing is related to the length of the expanded GAA-TR mutation in FRDA. METHODS: Patient-derived lymphoblastoid cell lines bearing a range of expanded alleles (200-1,122 triplets) were evaluated for FXN transcript levels by quantitative reverse transcriptase polymerase chain reaction. FXN promoter function was directly measured by quantitative analysis of transcriptional initiation via metabolic labeling of newly synthesized transcripts in living cells. RESULTS: FXN transcriptional deficiency was significantly correlated with the length of the shorter of the 2 expanded alleles, which was noted both upstream (R(2) = 0.84, p = 0.014) and downstream (R(2) = 0.89, p = 0.002) of the expanded GAA-TR mutation, suggesting that FXN promoter silencing in FRDA is related to repeat length. A bilinear regression model revealed that length dependence was strongest when the shorter of the 2 expanded alleles contained <400 triplets. Direct measurement of FXN promoter activity in patients with expanded alleles containing <400 versus >400 triplets in the shorter of the 2 expanded alleles revealed a significantly greater deficiency in individuals with longer GAA-TR alleles (p < 0.05). INTERPRETATION: FXN promoter silencing in FRDA is dependent on the length of the expanded GAA-TR mutation. PMID- 25112977 TI - Redefinition of the millipede subgenus Megaphyllum sensu stricto Verhoeff, 1894 and neotype designation for Megaphyllum austriacum (Latzel, 1884) (Myriapoda: Diplopoda: Julida: Julidae). AB - Megaphyllum sensu stricto, i.e. the nominotypical subgenus of the very complicated genus Megaphyllum Verhoeff, 1894, is redefined on the basis of examination of type and non-type material and literature data. Four species groups including twenty species in all are listed, and the identity of M. austriacum (C. L. Koch, 1838) is clarified with a proposal of neotype designation under ICZN Article 75.6. in order to stabilize the current usage of the name. Prevailing usage of M. silvaticum (Verhoeff, 1898) syn. nov. (nomen protectum) over the senior synonym M. nigrescens (Latzel, 1884) (nomen oblitum) is maintained under ICZN Article 23.9. M. banaticum (Verhoeff, 1899) is syn. nov. of M. erythronotum (Latzel, 1884) comb. nov., M. bosniense cotinophilum (Loksa, 1962) syn. nov. of M. bosniense bosniense (Verhoeff, 1897) and M. transsylvanicum transdanubicum (Loksa, 1962) syn. nov. of M. transsylvanicum transsylvanicum (Verhoeff, 1897). M. unilineatum (C. L. Koch, 1838) is new to the fauna of Turkey. PMID- 25112979 TI - Phamartes coronatus gen. nov. sp. nov. a new genus and species of stick insect from Bach Ma National Park, central Vietnam (Phasmida, Diapheromeridae, Necrosciinae). AB - A new genus and species of stick insect Phamartes coronatus gen. nov. sp. nov. from Bach Ma National Park, central Vietnam is described and illustrated from both sexes and the egg. The genus is most closely related to Oxyartes Stal, 1875, but easily distinguishable by the presence of fully developed alae, the head armature and the split and asymmetrical anal segment, a character previously unknown in Necrosciinae. PMID- 25112978 TI - Nematodes from galls on Myrtaceae. V. Fergusobia from large multilocular shoot bud galls from Angophora and Eucalyptus in Australia, with descriptions of six new species. AB - Six new species of Fergusobia, from large multilocular shoot bud galls on two species of Angophora and four species of Eucalyptus from both subgenera Eucalyptus and Symphyomyrtus, are described. Fergusobia cosmophyllae Davies n. sp. is characterized by the combination of a C-shaped parthenogenetic female with a short arcuate conoid tail, a broad (small a ratio) arcuate infective female with an hemispherical tail tip, and an arcuate to J-shaped male with broad, angular spicules and short bursa. Fergusobia delegatensae Davies n. sp. has an open C-shaped parthenogenetic female with a broadly conoid tail, an infective female of variable shape with an hemispherical tail tip, and a male of open C shape with a crenate bursa that arises 40-70% along the length of the body from the tail tip and terminates just anterior to the cloaca. Fergusobia diversifoliae Davies n. sp. has a C-shaped parthenogenetic female with a conoid tail, an arcuate infective female with a hemispherical tail tip, and an arcuate, C- or J shaped male with angular spicule and a long peloderan bursa. Fergusobia floribundae Davies n. sp. has a C-shaped parthenogenetic female with a narrow, arcuate, conoid tail, an arcuate infective female with a hemispherical tail tip, and an arcuate or J-shaped male with an angular spicule and a short to mid-body length peloderan bursa. Fergusobia minimus Lisnawita n. sp. has a C-shaped parthenogenetic female with a conoid tail, an arcuate to open C-shaped infective female with a hemispherical tail tip, and an arcuate to open C-shaped male with an angular spicule and a peloderan bursa arising at about 10-30% of body length. Fergusobia pimpamensis Davies n. sp. has an open C to C-shaped parthenogenetic female with a narrow conoid tail, an arcuate to open C-shaped infective female with a hemispherical tail tip, and an arcuate to C-shaped male with an arcuate spicule and a long, crenate, peloderan bursa. An inventory of all known Fergusobia/Fergusonina associations from terminal shoot bud galls is presented. The larval shield morphology of the associated mutualistic Fergusonina species is discussed where known. Analyses of DNA sequences of D2/D3 and COI suggested that the six new species are distributed between three clades of Fergusobia. PMID- 25112981 TI - A new species of Gamasiphis Berlese (Acari: Ologamasidae) from Russia (Sakhalin and Kuril Islands) with a key to the Asian species . AB - Gamasiphis ochotensis sp. n. is described based on the morphology of females and males collected from litter and soil in the Sakhalin and Kuril Islands of Far East Russia. A key for the separation of females of 10 recognisable species of Gamasiphis distributed in Asia is provided. PMID- 25112980 TI - Nematodes from galls on Myrtaceae. IV. Fergusobia from flat leaf galls on Eucalyptus and Corymbia, with descriptions of two new species. AB - Two new species of Fergusobia are described. Both were collected from flat leaf galls from South Australia, one on Eucalyptus microcarpa and the other on E. porosa. Fergusobia microcarpae n. sp. Davies is characterised by the combination of a C-shaped parthenogenetic female with a short, broadly rounded conoid tail, an arcuate to open C-shaped infective female with an hemispherical tail tip, and arcuate to J-shaped males with angular spicules and short peloderan bursa. Fergusobia porosae n. sp. Davies is similar in having an arcuate to C-shaped parthenogenetic female with a small conoid tail, an almost straight to arcuate infective female with an hemispherical tail tip, and males that are almost straight to barely J-shaped with angular spicules and short peloderan bursa. They differ in that the bodies of parthenogenetic and infective females of F. microcarpae n. sp. are more curved than in F. porosae n. sp. Other known similar forms of Fergusobia/Fergusonina galls are outlined and the larval shield morphologies of their associated mutualistic Fergusonina fly species are discussed where known. An inventory of all known Fergusobia/Fergusonina associations from flat leaf galls from Corymbia spp. and Eucalyptus spp. is presented. Relationships of Fergusobia nematodes were inferred from analysis of sequences of 28S rDNA D2/D3 domains and a portion of mitochondrial DNA cytochrome oxidase subunit I (mtCOI). Nematodes from flat leaf galls appeared in two clades. PMID- 25112982 TI - Species diversity in the Palaeotropical leaf-litter genus Apelaunothrips (Thysanoptera, Phlaeothripinae). AB - Species of Apelaunothrips are fungus-feeders on dead leaves, particularly in leaf litter, and they are recorded across the Old World tropics from Africa to northern Australia and southern Japan. All species in this genus have the maxillary stylets 4-6 microns in diameter, considerably broader than the 2-3 micron diameter that is typical among Phlaeothripinae. The species are largely uniform in structure, but in four species the larger males have fore femora enlarged with a conspicuous tubercle on the inner margin at the base. In one of these species, the males are dimorphic, with no intermediates between large and small individuals, in contrast to the continuous variation in structure found in many polymorphic Phlaeothripidae. A key is provided to the 37 recognised species of Apelaunothrips, including the following: A. desleyae sp.n. from northern Australia; A. bogor sp.n. from Java; A. gombak sp.n. from Peninsular Malaysia. PMID- 25112983 TI - A new, prairie-restricted species of Anacampsis Curtis (Lepidoptera: Gelechiidae) from Illinois . AB - Anacampsis wikeri (Lepidoptera: Gelechiidae), new species, is described. The larva of A. wikeri feeds on leaves of a prairie legume, leadplant, Amorpha canescens (Fabaceae). The moth is univoltine, with mature larvae occurring in late May; adults are active from early June into summer and autumn, while overwintering throughout the winter months. The adult of A. wikeri is externally very similar to that of another legume-feeding species, Anacampsis psoraliella. Sight identification of adults of these two species, especially of unreared individuals originating in the multi-state area of the Midwest in which their respective larval hostplants are sympatric, therefore is rendered problematic. Larval host plant specificity and adult genital morphology, however, allow unequivocal diagnosis. These characters are discussed, and male and female genitalia are illustrated for both species. PMID- 25112984 TI - Systematics, phylogeny and biology of a new genus of Lithocolletinae (Lepidoptera: Gracillariidae) associated with Cistaceae. AB - The gracillariid genus Triberta gen. nov. (Lepidoptera: Gracillariidae: Lithocolletinae Stainton, 1854) is described to accommodate two species formerly assigned to the genus Phyllonorycter Hubner, 1822: Triberta helianthemella (Herrich-Schaffer, 1861) comb. nov. and T. cistifoliella (Groschke, 1944) comb. nov. Triberta cistifoliella bona sp. is restored from synonymy based on morphological characters. The new genus is biologically associated with the plant family Cistaceae of the order Malvales and is endemic to the Palaearctics. Our molecular analysis of eleven nuclear genes failed to unambiguously place Triberta in the lithocolletine phylogeny, but revealed that this genus is distinct from either clade Phyllonorycter + Cremastobombycia and Cameraria. The distinctiveness of Triberta is also supported by inferred traits in wing venation, micro morphology of the last instar larva, pupa, genital morphology of the adult and life history. A key to the species of Triberta is provided. The interspecific homogeneity in external morphology, coupled with minor differences in genital traits, an apparent narrow specialization on Cistaceae host plants, restricted geographical range and molecular evidence based on multi-nuclear genes jointly suggest that the generic diversification of Triberta is a relatively old phenomenon and driven strongly by host selection. PMID- 25112985 TI - A new genus and species of Leptocheliidae (Crustacea: Peracarida: Tanaidacea) from Isla del Coco (Costa Rica). AB - Samples from the scarcely-studied sedimentary seabed from the Isla del Coco (Costa Rica) yielded a single species of Tanaidacea, belonging to a new genus of Leptocheliidae, Cocotanais. The new genus shows affinities with Pseudonototanais and Heterotanais in bearing a conspicuous forcipate cheliped in the males, which in Cocotanais has a modified merus and carpal flange. Other distinct characters of the males are a triangular cephalothorax, a three-articled antennular peduncle and swollen bases of pereopods 4-6. Females have a four-articled antennule, a maxilliped endite with three distal flat spines and two inner coupling hooks, and a maxilliped basis with two long setae. The species was found in sheltered bays, both free-living in the sediment and also as a commensal of anemones (Infraorder Boloceroidaria), thus representing the first reported case of such an association. PMID- 25112987 TI - Discovery of four new species of the genus Planaeschna from Southwestern China (Odonata: Anisoptera: Aeshnidae). AB - Four new species of the genus Planaeschna, P. robusta sp. nov. (holotype male; Mt. Emeishan, Emeishan City, Sichuan Province, China, 16. VIII. 2007), P. maculifrons sp. nov. (holotype male; Mt. Emeishan, Emeishan City, Sichuan Province, China, 20. VIII. 2007), P. caudispina sp. nov. (holotype male; Mt. Qingchengshan, Dujiangyan City, Sichuan Province, China, 30. VIII. 2007) and P. monticola sp. nov. (holotype male; Sanjiacun Stream, Fengyi Town, Dali City, Yunnan Province, China, 19. XI. 2012) are described and illustrated and diagnosed from their congeners. All the holotypes have been deposited in the Collection of Aquatic Animals, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan City, Hubei Province, China. Brief notes on the biology of each species are also provided. PMID- 25112988 TI - Description of larva, redescription of adults and biology of Mortogenesia mesopotamica (Morton, 1921) (Ephemeroptera: Palingeniidae). AB - All life stages of Mortogenesia mesopotamica (Morton, 1921) are described, on the basis of material collected in the lower Euphrates-Tigris River basin. Adults are redescribed, and larvae are described for the first time, based on sets of larval exuviae. The monotypic genus Mortogenesia Lestage, 1923 is redefined using both adult and larval characteristics: eyes not contiguous, distinctly separated by a wide gap; vestigial mandibular tusks present, with 3-4 rounded lateral projections; forewing veins MP1 and iMP not brought together; CuA furcation absent on forewing; both claws similarly shaped in males; hind tarsi five-segmented; penes with roughly triangular, apically rounded and divergent lobes (in adults); seven conspicuous stout teeth on outer margin of mandibular tusk, with no apical spine-like setae; maxillary palps two-segmented; distal segment of labial palps asymmetric and bulbous; basal segment of labial palps densely pilose; forelegs with relatively short, triangular claws that are basally wider than tarsi; foretibiae with stout spines only; and a simple, leaf-like gill 1 (in larvae). The burrowing larvae of M. mesopotamica occur solely in large permanent lowland rivers, in clayey or muddy sediments, with particles exceeding 0.025-0.075 mm. Based on observations of their burrows, larval density is approximately 100-200 individuals per square meter. Various evidence suggests a unique phenomenon of male neoteny in Mortogenesia. Preliminary results of male dissections suggests a missing teneral adult cuticle, and male "subimagoes" and females occur simultaneously after oviposition. Mortogenesia mesopotamica is known currently from the Euphrates-Tigris basin in Iraq and from the Karkheh River in Iran. PMID- 25112989 TI - New pseudophyllinae from the Lesser Antilles (Orthoptera: Ensifera: Tettigoniidae). AB - Two new Cocconitini Brunner von Wattenwyl, 1895 species belonging to Nesonotus Beier, 1960 are described from the Lesser Antilles: Nesonotus caeruloglobus Hugel, n. sp. from Dominica, and Nesonotus vulneratus Hugel, n. sp. from Martinique. The songs of both species are described and elements of biology are given. The taxonomic status of species close to Nesonotus tricornis (Thunberg, 1815) is discussed. PMID- 25112986 TI - Pachybrachis holerorum (Coleoptera: Chrysomelidae: Cryptocephalinae), a new species from the Apennines, Italy, identified by integration of morphological and molecular data. AB - Pachybrachis holerorum n. sp. is described from the northern Apennines, Italy. The new species is related to P. karamani (Weise, 1893), from which it differs in the shape of the median lobe of the aedeagus and in small differences in chromatic pattern. The close relationship with P. karamani is confirmed by molecular analyses performed on a fragment of 829 nucleotides of the mitochondrial gene Cytochrome c oxidase subunit 1 (cox1). The general mixed Yule coalescent model, developed for species delimitation using single-locus molecular data, was applied to a cox1 phylogeny in order to test the hypothesis of P. holerorum as a separate species. Information on the host plants, acquired during specimen collection, was confirmed from gut content, targeting a fragment of the plastid large subunit of the ribulose-bisphosphate carboxylase gene and the trnL(UAA) intron. Besides, the lectotype of P. karamani is designated. PMID- 25112990 TI - The Phyllomedusa perinesos group (Anura: Hylidae) is derived from a Miocene Amazonian Lineage. AB - The Phyllomedusa perinesos group is composed of four species that inhabit cloud forests in the eastern Andean slopes. We estimated the phylogenetic relationships among them and their closest relatives using mitochondrial DNA sequences. Our results confirm the monophyly of the group and a close relationship with the Amazonian species Phyllomedusa atelopoides and Phyllomedusa tomopterna. A chronogram indicates that the group originated during the Miocene and the contemporary species diverged from their closest relatives during the Miocene and early Pliocene. The timing of the group's origin suggests that its evolution was linked to the rise of the eastern Andes. Based on the phylogeny we expand the species content of the group to include P. atelopoides and P. tomopterna. PMID- 25112991 TI - Why Drosophila is not Drosophila any more, why it will be worse and what can be done about it? PMID- 25112992 TI - Tersilochinae of Western Amazonia (Hymenoptera: Ichneumonidae). Genus Stethantyx Townes, part 1. AB - Sixteen species of the genus Stethantyx Townes having first and second sections of radius meeting at obtuse angle are recorded from Peru and Ecuador in Western Amazonia. Ten species, S. amazonica Khalaim & Saaksjarvi, sp. nov., S. aurantia Khalaim & Saaksjarvi, sp. nov., S. juninensis Khalaim & Bordera, sp. nov., S. loretosa Khalaim & Saaksjarvi, sp. nov., S. neopropodeator Khalaim & Saaksjarvi, sp. nov., S. orellana Khalaim & Saaksjarvi, sp. nov., S. sinuata Khalaim & Saaksjarvi, sp. nov., S. tiputinia Khalaim & Saaksjarvi, sp. nov., S. trepida Khalaim & Saaksjarvi, sp. nov. and S. voluptaria Khalaim & Saaksjarvi, sp. nov., are described as new. Six species, previously known only from Costa Rica, S. alajuela Khalaim & Broad, S. heredia Khalaim & Broad, S. orosia Khalaim & Broad, S. propodeator Khalaim & Broad, S. puntarenasa Khalaim & Broad and S. sanjosea Khalaim & Broad, are recorded from South America for the first time. A partial key to Western Amazonian species of Stethantyx is given. PMID- 25112993 TI - Makoiamya cotterallae, a new genus and species of bivalve (Ceratomyidae) from the latest Triassic of New Zealand and New Caledonia. AB - The new genus and species Makoiamya cotterallae is erected for fossil bivalves previously informally identified as Anodontophora Alberti (= Unionites Wissmann) or a relative or Ochotomya Polubotko in the Late Triassic Murihiku Terrane of New Zealand and Teremba Terrane of New Caledonia (Norian and Rhaetian; Warepan and Otapirian local stages). Neither of these genera happily accommodates these shells and a new genus is considered necessary for them. Makoiamya fits most readily into the Ceratomyidae and members were burrowers in fine sand and silt, where they are generally preserved in life orientation. PMID- 25112994 TI - New species and new records of the hygropetric water beetle genus Oocyclus Sharp from South America (Coleoptera: Hydrophilidae). AB - Three new species of Oocyclus Sharp, 1882 are described from tropical South America: O. maluz sp. n. (Venezuela), O. miza sp. n. (Venezuela), and O. brunneus sp. n. (Bolivia). New distributional records are provided for O. andinus Short & Garcia, O. coromoto Short & Garcia (newly recorded from Suriname), O. floccus Short & Garcia (newly recorded from Guyana and Suriname), O. iguazu (Oliva), O. meridensis Short & Garcia, O. petra Short & Garcia (newly recorded from Guyana and Suriname), O. trio Short & Kadosoe (newly recorded from Guyana), O. trujillo Short & Garcia, and O. yubai Clarkson & Short (newly recorded from Paraguay). Updates to the keys of the Brazilian and Venezuelan Oocyclus species are provided. PMID- 25112995 TI - Fecenia travancoria Pocock is recognised as a junior synonym of Fecenia protensa Thorell (Araneae: Psechridae): a case of intraspecific variation . PMID- 25112996 TI - Armadillogorgia albertoi sp. nov.: a new primnoid from the Argentinean deep sea. AB - Eleven specimens of a new species of primnoid from the Argentinean deep sea are here presented. Armadillogorgia albertoi sp. nov. differs from A. cyathella Bayer, 1980 in colony and polyp morphology, abaxial sclerite number and shape. It is the second species of the hitherto monospecific genus, and the northernmost record of the genus. PMID- 25112997 TI - Description of a new species of the genus Neolucanus Thomson, 1862 (Coleoptera: Lucanidae) from central Vietnam. AB - Neolucanus baongocae new species is described from Lam Dong Province (Central Vietnam) and compared to closely related Neolucanus taxa. PMID- 25112999 TI - Two species of Thienemanniella Kieffer from Oriental China (Diptera: Chironomidae: Orthocladiinae). AB - A new species from Oriental China, Thienemanniella curva sp. n. is described and illustrated as adult males. T. nipponica which belong to eye bare species group in Thienemanniella from Guangdong Province is re-described. A revised key to known males of the world is provided. PMID- 25112998 TI - Redescription of Osmylus multiguttatus McLachlan, 1870 (Neuroptera: Osmylidae) with distributional remarks. AB - Osmylus multiguttatus McLachlan, 1870 has recently been rediscovered in the Middle Anatolia. Redescription of the male and female is presented. Faunistic data and habitat are provided. Photograph of wings, drawings of male and female external and internal genitalia are illustrated for the first time. The distribution map with new recording sites and recent data is also given. A preliminary key to species of Osmylus is presented. PMID- 25113000 TI - A replacement name for Macrobrachium aemulum madhusoodani Pillai & Unnikrishnan, 2013, a junior homonym of Macrobrachium madhusoodani Unnikrishnan, Pillai & Jayachandran, 2011 (Decapoda: Palaemonidae) . PMID- 25113002 TI - Phylogenetic relationships of Tectoribates: nymphal characters of new North American species place the genus in Tegoribatidae (Acari, Oribatida). AB - Species in the oribatid mite genus Tectoribates are primarily Palaearctic and Neotropical, with scattered, unidentified records from North America. Herein, we describe 3 new Tectoribates species from dry forest and prairie habitats in North America: T. alcecampestris sp. nov., from Alberta, T. borealis sp. nov., from southern Alberta and Ontario, both on the basis of adults and nymphs, and T. campestris sp. nov., from dry grassland habitats in Ontario and Kansas, on the basis of adults. We provide a revised and expanded diagnosis for adults of Tectoribates. We assess relationships of Tectoribates, using characters of adults and newly discovered apheredermous, plicate immatures. We include observations on Pseudotectoribates which is closely related to Tectoribates. The closest relatives of these genera are hypothesised to be among the Tegoribatidae (Achipterioidea) rather than among the Achipteriidae (Achipterioidea), Oribatellidae (Oribatelloidea), or Ceratozetoidea, as suggested in previous classifications. Finally, we give a key to adults of the world fauna of Tectoribates. PMID- 25113003 TI - A revision of the New World sharpshooter genus Xyphon Hamilton (Hemiptera: Cicadellidae: Cicadellinae). AB - A phylogenetic analysis of Xyphon was completed using 45 adult morphological characters and 1,076 base pairs of the mtDNA gene NADH dehydrogenase 1. Multiple specimens, representative of the range of morphological variation found in each previously described species, were scored for the morphological data matrix to test the monophyly of each species. These tests supported the following synonymies: Xyphon gillettei (Ball, 1901) to include X. balli (Knull, 1940) syn. nov.; and X. reticulatum (Signoret, 1854) to include X. diductum (Fowler, 1900) syn. nov., X. dyeri (Gibson, 1919) syn. nov., and X. sagittiferum (Uhler, 1895) syn. nov. Parsimony and Bayesian techniques were used to infer relationships among species, resulting in almost identical tree topologies. In all analyses Xyphon was monophyletic and Draeculacephala was its sister genus although clade support for Xyphon was generally low. The analyses suggest that a clade comprising X. flaviceps (Riley) and X. fulgidum (Nottingham) is sister to the remainder of the genus, and a clade comprising X. gillettei and X. spadice sp. nov. was sister to a clade containing X. triguttatum (Nottingham), X. nudum (Nottingham), and X. reticulatum. The six currently recognized species, including X. spadice sp. nov., are described and illustrated and a key to adult Xyphon is provided. PMID- 25113001 TI - Using various lines of evidence to identify Chironomus species (Diptera: Chironomidae) in eastern Canadian lakes. AB - Chironomus Meigen (Diptera, Chironomidae) larvae are usually the largest sediment burrowing chironomids, and as such often constitute a major part of the freshwater infaunal biomass. However, use of this genus in ecological, environmental and paleoecological studies is hampered by the fact that Chironomus larvae are difficult to identify to species because the larvae of many species are morphologically similar. We used a combination of morphological, cytological and genetic techniques to distinguish Chironomus larvae collected from 31 water bodies located in eastern Canada, producing 17 distinguishable groupings. These groups of larvae were ultimately identified as belonging to 14 known species (C. anthracinus, C. bifurcatus, C. cucini, C. decorus-group sp. 2, C. dilutus, C. entis, C. frommeri, C. harpi, C. maturus, C. nr. atroviridis (sp. 2i), C. ochreatus, C. plumosus, C. staegeri and C. 'tigris') and three other species that remain unidentified (C. sp. NAI-III). No single approach served to delimit and identify larvae of all 17 Chironomus species that we collected. Although we expected that morphological criteria alone would be insufficient, our results suggest that DNA barcoding, using either the mitochondrial cox1 or the nuclear gb2beta gene, was also inadequate for separating some Chironomus species. Thus we suggest that multiple approaches will often be needed to correctly identify Chironomus larvae to species. PMID- 25113004 TI - Description of larvae of two closely related species Cassida palaestina Reiche, 1858 and Cassida rubiginosa Muller, 1776 (Coleoptera: Chrysomelidae: Cassidinae). AB - Larvae of two closely related species Cassida palaestina Reiche, 1858 and Cassida rubiginosa Muller, 1776 are described in detail including SEM microstructures. First instars are extremely similar with no clear diagnostic characters, larvae of Cassida palaestina are slightly more contrastingly coloured than larvae of C. rubiginosa, the latter having darker scoli, basal part of supra-anal processes and legs. Last instars differ in very subtle but constant characters: lateral scoli of C. palaestina are slightly shorter than those of C. rubiginosa, in C. palaestina tops of the lateral branches are armed apically with an elongate cauliflower-shaped sensillum while in C. rubiginosa tops of the lateral branches are more often armed with a pointed seta than with an elongate cauliflower-shaped sensillum, and cauliflower-shaped sensilla on tergites are less elongate in C. palaestina than in C. rubiginosa. These differences accompanied by distinguishing characters of adults and their distribution range indicate that both taxa are probably vicariant species with partial parapatric occurrence. Centaurea behen is a new host plant for C. palaestina. PMID- 25113005 TI - Review of the genus Hemistola Warren, 1893 in Taiwan with notes on an unusual conifer-feeding larva and descriptions of three new species (Lepidoptera, Geometridae, Geometrinae). AB - The genus Hemistola Warren, 1893 in Taiwan is reviewed. Seven species are confirmed, with descriptions of three new species provided: H. piceacola sp. nov., H. fui sp. nov. and H. taiwanensis sp. nov. The immature stages and unusual conifer-feeding behavior of H. piceacola on Taiwan spruce (Picea morrisonicola) are reported. The distribution of H. tenuilinea (Alpheraky, 1897) is discussed and this species is omitted from the Taiwanese fauna. PMID- 25113006 TI - Review of the genus Anasta Emeljanov (Hemiptera: Dictyopharidae: Hastini) from the Australasian region. AB - The dictyopharid planthopper genus Anasta Emeljanov from the Australasian region is revised to include six species including a new one: A. australiaca (Lallemand, 1935) comb. nov. (North Australia), A. lobosa sp. nov. (Papua New Guinea), A. minuta (Lallemand, 1935) comb. nov. (Timor, Indonesia), A. prognatha (Distant, 1906) (North Australia, Papua New Guinea), A. timorina (Lallemand, 1935) (Timor, Indonesia), and A. vitiensis Emeljanov et Wilson, 2009 (Fiji). Descriptions or redescriptions of A. australiaca, A. lobosa sp. nov., and A. prognatha are provided together with dorsal habitus and structural illustrations of male genitalia. A key to the species of the genus and distribution map are provided. The biogeography of the genus is discussed. PMID- 25113008 TI - Mooreonuphis vespa, a new brooding species of Onuphidae (Annelida) from northern Spain (Bay of Biscay). AB - A new species of the genus Mooreonuphis Fauchald, 1982 collected from the Cantabrian shelf (Bay of Biscay) is described. Mooreonuphis vespa sp. nov. constitutes the first record of this genus in European waters and is characterised by: conspicuous dark brown transverse segmental pigment bands; antennae and palps with 3-5 basal ceratophoral rings and a very long distal ring; unusually long and slender peristomial and dorsal cirri; simple branchiae from chaetiger 17-19. We present observations on its reproductive biology (including brooding behaviour) and remark on the biogeography of the genus. PMID- 25113007 TI - A molecular phylogeny recovers Strabomantis aramunha Cassimiro, Verdade and Rodrigues, 2008 and Haddadus binotatus (Spix, 1824) (Anura: Terrarana) as sister taxa. AB - The taxonomic and biogeographic affinities of Strabomantis aramunha from the Campos Rupestres of Brazil are intriguing. A unique skull morphology of females suggest affinities with the broad-headed eleutherodactylines of Northwestern South America in the genus Strabomantis. Male and juvenile morphology nonetheless suggest S. aramunha could be related to members of the recently described genus Haddadus from eastern Brazil. We assess the affinities of S. aramunha using molecular phylogenetic analyses of mitochondrial (12S, tRNAval, 16S, cyt b) and nuclear sequences (RAG-1and rhodopsin). Bayesian inference, likelihood, and parsimony analysis recover a highly supported clade with S. aramunha and H. binotatus as sister taxa. Accordingly, we transfer S. aramunha to Haddadus, and provide a new generic definition of the later. The distribution of species in Haddadus (highlands of the Espinhaco mountain Range and coastal eastern Brazil) is now concordant with the general pattern observed for other species in the area. PMID- 25113009 TI - Eviota santanai, a new Dwarfgoby from Timor-Leste (Teleostei: Gobiidae). AB - Eviota santanai is described based on four specimens from Timor-Leste, taken in 5 8 m depth. In general coloration pattern, the species is most similar to E. latifasciata, but differs in the cephalic sensory-pore system pattern, the absence of an occipital spot, and live color including pinkish-mauve bars. Eviota santanai has a dorsal/anal fin-ray formula of 8/8, 5th pelvic-fin ray absent, some lower pectoral-fin rays branched, and IT and PITO pores absent. PMID- 25113010 TI - Ebola and other viral haemorrhagic fevers. PMID- 25113011 TI - Correlation between the retroversion of the humeral head and the orientation of the intertubercular sulcus: a CT scan anatomical study. AB - PURPOSE: The purpose was to study the anatomy of the humeral head, more specifically the retroversion of the humeral head and the orientation of the intertubercular sulcus, using CT scan, and to make correlations between those two entities of the proximal humerus. METHODS: Sixty dry adult humeri from an osteological collection underwent CT scan from the proximal to the distal extremity. The measurements obtained by CT-reformation were recorded by two independent radiologists. We determined the humeral head axis, the transepicondylar axis, the retroversion of the humeral head, and the orientation of the intertubercular sulcus (ITS). Statistical analysis using SPSS determined the Pearson correlation coefficient. RESULTS: The CT scan measurements were similar to those in the literature, and thus allowed us to validate CT scan assessment. Statistical analysis showed a significant reverse correlation [the coefficient of correlation was -0.37 (p = 0.004)] between the retroversion of the humeral head and the orientation of the intertubercular sulcus: the more the retroversion of the humeral head increases, the more the angle of the orientation of the ITS decreases. CONCLUSIONS: To the best of our knowledge, this reverse correlation between the retroversion of the humeral head and the orientation of the intertubercular sulcus has never been described. This new anatomical data might be helpful for orthopedic surgery. PMID- 25113012 TI - Is coxa valga a predictor for the severity of knee osteoarthritis? A cross sectional study. AB - PURPOSE: In the present study, we aimed to evaluate the affect of the variations in hip anatomy and pelvic geometry on the severity of knee OA. METHODS: Idiopathic knee OA patients fulfilling the clinical criteria of American College of Rheumatology for OA were enrolled in the study. Several measurements regarding the hip and pelvis were performed on pelvic radiographs. Each knee was graded according to the Kellgren and Lawrence (KL) radiographic system (0-4) along with a categorization in accordance with the medial tibiofemoral joint space widths (JSW). RESULTS: The study group consisted of 111 subjects. The inner and outer pelvic diameters were getting wider as the JSW grade increased. Likewise, among the hip measurements, femoral head, neck and shaft diameters and hip axis lengths were linked with KL grade. There were significant differences in neck-shaft angle (NSA) between groups of JSW with a highest NSA in JSW grade 3. The optimal cut off value for NSA in predicting the severity of knee OA was 134.4 degrees . Furthermore, NSA beyond 134.4 degrees was found to increase the risk of severe knee OA eightfold. CONCLUSIONS: Variations in pelvic geometry and hip anatomy are associated with the severity of knee OA. People with NSA of above 134.4 degrees have eightfold increased risk of developing severe knee OA. Pelvic radiographies could be evaluated at younger ages-particularly in people with high genetic predispositions-to identify the individuals at high risk and in turn, to tailor the preventive measures to these subjects. PMID- 25113013 TI - Purification and characterization of a novel alkaline beta-1,3-1,4-glucanase (lichenase) from thermophilic fungus Malbranchea cinnamomea. AB - A novel alkaline beta-1,3-1,4-glucanase (McLic1) from a thermophilic fungus, Malbranchea cinnamomea, was purified and biochemically characterized. McLic1 was purified to homogeneity with a purification fold of 3.1 and a recovery yield of 3.7 %. The purified enzyme was most active at pH 10.0 and 55 degrees C, and exhibited a wide range of pH stability (pH 4.0-10.0). McLic1 displayed strict substrate specificity for barley beta-glucan, oat beta-glucan and lichenan, but did not show activity towards other tested polysaccharides and synthetic p nitrophenyl derivates, suggesting that it is a specific beta-1,3-1,4-glucanase. The K m values for barley beta-glucan, oat beta-glucan and lichenan were determined to be 0.69, 1.11 and 0.63 mg mL(-1), respectively. Moreover, the enzyme was stable in various non ionic surfactants, oxidizing agents and several commercial detergents. Thus, the alkaline beta-1,3-1,4-glucanase may have potential in industrial applications, such as detergent, paper and pulp industries. PMID- 25113014 TI - Metal-free hydrogenation catalyzed by an air-stable borane: use of solvent as a frustrated Lewis base. AB - In recent years 'frustrated Lewis pairs' (FLPs) have been shown to be effective metal-free catalysts for the hydrogenation of many unsaturated substrates. Even so, limited functional-group tolerance restricts the range of solvents in which FLP-mediated reactions can be performed, with all FLP-mediated hydrogenations reported to date carried out in non-donor hydrocarbon or chlorinated solvents. Herein we report that the bulky Lewis acids B(C6Cl5)x(C6F5)(3-x) (x=0-3) are capable of heterolytic H2 activation in the strong-donor solvent THF, in the absence of any additional Lewis base. This allows metal-free catalytic hydrogenations to be performed in donor solvent media under mild conditions; these systems are particularly effective for the hydrogenation of weakly basic substrates, including the first examples of metal-free catalytic hydrogenation of furan heterocycles. The air-stability of the most effective borane, B(C6Cl5)(C6F5)2, makes this a practically simple reaction method. PMID- 25113015 TI - Partial proportional odds model-an alternate choice for analyzing pedestrian crash injury severities. AB - The conventional methods for crash injury severity analyses include either treating the severity data as ordered (e.g. ordered logit/probit models) or non ordered (e.g. multinomial models). The ordered models require the data to meet proportional odds assumption, according to which the predictors can only have the same effect on different levels of the dependent variable, which is often not the case with crash injury severities. On the other hand, non-ordered analyses completely ignore the inherent hierarchical nature of crash injury severities. Therefore, treating the crash severity data as either ordered or non-ordered results in violating some of the key principles. To address these concerns, this paper explores the application of a partial proportional odds (PPO) model to bridge the gap between ordered and non-ordered severity modeling frameworks. The PPO model allows the covariates that meet the proportional odds assumption to affect different crash severity levels with the same magnitude; whereas the covariates that do not meet the proportional odds assumption can have different effects on different severity levels. This study is based on a five-year (2008 2012) national pedestrian safety dataset for Switzerland. A comparison between the application of PPO models, ordered logit models, and multinomial logit models for pedestrian injury severity evaluation is also included here. The study shows that PPO models outperform the other models considered based on different evaluation criteria. Hence, it is a viable method for analyzing pedestrian crash injury severities. PMID- 25113016 TI - Delayed presentation of cerebellar and spinal cord infarction as a complication of computed tomography-guided transthoracic lung biopsy: a case report. AB - INTRODUCTION: Computed tomography-guided transthoracic needle biopsy is a common diagnostic procedure that is associated with various complications including pneumothorax, parenchymal hemorrhage, and hemoptysis. A systemic air embolism is a very rare (0.06 to 0.21%) but potentially fatal complication. CASE PRESENTATION: A 70-year-old Korean male was admitted to our hospital for evaluation of a solitary pulmonary nodule located adjacent to the right inferior pulmonary vein in the medial basal segment of the right lower lobe. A computed tomography-guided needle biopsy was performed by a radiologist using a coaxial needle. A computed tomography image obtained immediately after the biopsy showed intraluminal free air in the proximal ascending aorta. He complained of a mild electrical current sensation in both lower extremities. After three hours he complained of neurological deficit in both lower extremities as well as voiding difficulty. The brain and spine magnetic resonance images showed a right cerebellar and spinal cord infarction at the T8-10 levels. CONCLUSIONS: We report a case of air embolism to the cerebellum and spinal cord causing infarction presenting with an initial symptom of mild electrical current sensation in both lower extremities during the transthoracic needle biopsy. For this potentially fatal complication, early recognition, followed by prompt therapy is critical to reducing morbidity and mortality. PMID- 25113018 TI - A simple formula for quick and accurate calculation of maximum allowable volume of local anaesthetic agents. PMID- 25113017 TI - Is there any role for community involvement in the community-based health planning and services skilled delivery program in rural Ghana? AB - BACKGROUND: In Ghana, between 1,400 and 3,900 women and girls die annually due to pregnancy related complications and an estimated two-thirds of these deaths occur in late pregnancy through to 48 hours after delivery. The Ghana Health Service piloted a strategy that involved training Community Health Officers (CHOs) as midwives to address the gap in skilled attendance in rural Upper East Region (UER). CHO-midwives collaborated with community members to provide skilled delivery services in rural areas. This paper presents findings from a study designed to assess the extent to which community residents and leaders participated in the skilled delivery program and the specific roles they played in its implementation and effectiveness. METHODS: We employed an intrinsic case study design with a qualitative methodology. We conducted 29 in-depth interviews with health professionals and community stakeholders. We used a random sampling technique to select the CHO-midwives in three Community-based Health Planning and Services (CHPS) zones for the interviews and a purposive sampling technique to identify and interview District Directors of Health Services from the three districts, the Regional Coordinator of the CHPS program and community stakeholders. RESULTS: Community members play a significant role in promoting skilled delivery care in CHPS zones in Ghana. We found that community health volunteers and traditional birth attendants (TBAs) helped to provide health education on skilled delivery care, and they also referred or accompanied their clients for skilled attendants at birth. The political authorities, traditional leaders, and community members provide resources to promote the skilled delivery program. Both volunteers and TBAs are given financial and non-financial incentives for referring their clients for skilled delivery. However, inadequate transportation, infrequent supply of drugs, attitude of nurses remains as challenges, hindering women accessing maternity services in rural areas. CONCLUSIONS: Mutual collaboration and engagement is possible between health professionals and community members for the skilled delivery program. Community leaders, traditional and political leaders, volunteers, and TBAs have all been instrumental to the success of the CHPS program in the UER, each in their unique way. However, there are problems confronting the program and we have provided recommendations to address these challenges. PMID- 25113019 TI - Proof of concept trial on changes in current perception threshold after sacral neuromodulation. AB - OBJECTIVES: Sacral neuromodulation (SNM) is theorized to alter the neural pathways that mediate bladder and urethral sensation. We hypothesize that SNM affects current perception thresholds (CPTs) of afferent sensory nerve pathways. MATERIALS AND METHODS: Eight women were enrolled and completed pre and postoperative testing. A CPT device was used to measure CPT at 5 Hz (C-fibers), 250 Hz (Adelta-fibers), and 2000 Hz (Abeta-fibers) on the urethra and bladder prior to and one month after SNM. Index finger readings at 2000 Hz served as controls. RESULTS: SNM had the greatest effect on the bladder at 250 and 2000 Hz, suggesting reduced bladder sensitivity. Significant changes in CPT were seen in the bladder at 2000 Hz with a decrease in sensitivity (p = 0.033). CPT testing was well tolerated, and no adverse events were identified. CONCLUSIONS: With a measurable change in CPT values for Adelta-fibers and Abeta-fibers, these findings suggest that SNM modulates large myelinated afferent fibers in the bladder. Notably, little or no changes were found in the C-fiber CPT measurements. More research is needed with a larger sample size to determine the significance of these findings. PMID- 25113020 TI - Temporal dynamics of eye movements are related to differences in scene complexity and clutter. AB - Recent research has begun to explore not just the spatial distribution of eye fixations but also the temporal dynamics of how we look at the world. In this investigation, we assess how scene characteristics contribute to these fixation dynamics. In a free-viewing task, participants viewed three scene types: fractal, landscape, and social scenes. We used a relatively new method, recurrence quantification analysis (RQA), to quantify eye movement dynamics. RQA revealed that eye movement dynamics were dependent on the scene type viewed. To understand the underlying cause for these differences we applied a technique known as fractal analysis and discovered that complexity and clutter are two scene characteristics that affect fixation dynamics, but only in scenes with meaningful content. Critically, scene primitives-revealed by saliency analysis-had no impact on performance. In addition, we explored how RQA differs from the first half of the trial to the second half, as well as the potential to investigate the precision of fixation targeting by changing RQA radius values. Collectively, our results suggest that eye movement dynamics result from top-down viewing strategies that vary according to the meaning of a scene and its associated visual complexity and clutter. PMID- 25113021 TI - The role of color in expert object recognition. AB - In the current study, we examined how color knowledge in a domain of expertise influences the accuracy and speed of object recognition. In Experiment 1, expert bird-watchers and novice participants categorized common birds (e.g., robin, sparrow, cardinal) at the family level of abstraction. The bird images were shown in their natural congruent color, nonnatural incongruent color, and gray scale. The main finding was that color affected the performance of bird experts and bird novices, albeit in different ways. Although both experts and novices relied on color to recognize birds at the family level, analysis of the response time distribution revealed that color facilitated expert performance in the fastest and slowest trials whereas color only helped the novices in the slower trials. In Experiment 2, expert bird-watchers were asked to categorize congruent color, incongruent color, and gray scale images of birds at the more subordinate, species level (e.g., Nashville warbler, Wilson's warbler). The performance of experts was better with congruent color images than with incongruent color and gray scale images. As in Experiment 1, analysis of the response time distribution showed that the color effect was present in the fastest trials and was sustained through the slowest trials. Collectively, the findings show that experts have ready access to color knowledge that facilitates their fast and accurate identification at the family and species level of recognition. PMID- 25113023 TI - Pre-hospital care: a critical phase of the acute cardiovascular care management process. PMID- 25113022 TI - A simple biophysically plausible model for long time constants in single neurons. AB - Recent work in computational neuroscience and cognitive psychology suggests that a set of cells that decay exponentially could be used to support memory for the time at which events took place. Analytically and through simulations on a biophysical model of an individual neuron, we demonstrate that exponentially decaying firing with a range of time constants up to minutes could be implemented using a simple combination of well-known neural mechanisms. In particular, we consider firing supported by calcium-controlled cation current. When the amount of calcium leaving the cell during an interspike interval is larger than the calcium influx during a spike, the overall decay in calcium concentration can be exponential, resulting in exponential decay of the firing rate. The time constant of the decay can be several orders of magnitude larger than the time constant of calcium clearance, and it could be controlled externally via a variety of biologically plausible ways. The ability to flexibly and rapidly control time constants could enable working memory of temporal history to be generalized to other variables in computing spatial and ordinal representations. PMID- 25113026 TI - Social solidarity and the right to health: essential elements for people-centred health systems. PMID- 25113025 TI - "It's Not that Easy"--Medical Students' Fears and Barriers in End-of-Life Communication. AB - This study aims to assess and improve communication education for medical students in palliative care (PC) with the use of simulated patients (SP) in Germany. More specifically, to explore how students evaluate the use of SP for end-of-life communication training and which fears and barriers arise. A pilot course was implemented. Qualitative content analysis was used to analyse transcribed recordings of the course. Pre- and post-course questionnaires containing open-ended questions ascertained students' motivation for participating, their preparation within their degree programme and whether they felt they had learned something important within the course. Seventeen medical students in their third to fourth year of education (age 22-31) participated in the five-session course and answered the questionnaires (pre n = 17, post n = 12). Students felt insufficiently prepared and insecure. Discussing end-of-life issues was experienced as challenging and emotionally moving. Within the conversations, although students sometimes showed blocking behaviour in reaction to emotional impact, they valued the consideration of emotional aspects as very important. The course was overall highly appreciated and valued as being helpful. The communication situation with the SP was perceived as authentic. Ten out of 12 students confirmed to have learned something important (post course). Our results indicate an urgent need for better communication training for medical students. Due to the fact that bedside teaching in PC is not feasible for all students, training with standardized SP can be a way to generate an authentic learning situation. Techniques to address fears and blocking behaviour should, however, also be considered. PMID- 25113024 TI - ABC inference of multi-population divergence with admixture from unphased population genomic data. AB - Rapidly developing sequencing technologies and declining costs have made it possible to collect genome-scale data from population-level samples in nonmodel systems. Inferential tools for historical demography given these data sets are, at present, underdeveloped. In particular, approximate Bayesian computation (ABC) has yet to be widely embraced by researchers generating these data. Here, we demonstrate the promise of ABC for analysis of the large data sets that are now attainable from nonmodel taxa through current genomic sequencing technologies. We develop and test an ABC framework for model selection and parameter estimation, given histories of three-population divergence with admixture. We then explore different sampling regimes to illustrate how sampling more loci, longer loci or more individuals affects the quality of model selection and parameter estimation in this ABC framework. Our results show that inferences improved substantially with increases in the number and/or length of sequenced loci, while less benefit was gained by sampling large numbers of individuals. Optimal sampling strategies given our inferential models included at least 2000 loci, each approximately 2 kb in length, sampled from five diploid individuals per population, although specific strategies are model and question dependent. We tested our ABC approach through simulation-based cross-validations and illustrate its application using previously analysed data from the oak gall wasp, Biorhiza pallida. PMID- 25113027 TI - Economic cost of primary prevention of cardiovascular diseases in Tanzania. AB - Tanzania is facing a double burden of disease, with non-communicable diseases being an increasingly important contributor. Evidence-based preventive measures are important to limit the growing financial burden. This article aims to estimate the cost of providing medical primary prevention interventions for cardiovascular disease (CVD) among at-risk patients, reflecting actual resource use and if the World Health Organization (WHO)'s CVD medical preventive guidelines are implemented in Tanzania. In addition, we estimate and explore the cost to patients of receiving these services. Cost data were collected in four health facilities located in both urban and rural settings. Providers' costs were identified and measured using ingredients approach to costing and resource valuation followed the opportunity cost method. Unit costs were estimated using activity-based and step-down costing methodologies. The patient costs were obtained through a structured questionnaire. The unit cost of providing CVD medical primary prevention services ranged from US$30-41 to US$52-71 per patient per year at the health centre and hospital levels, respectively. Employing the WHO's absolute risk approach guidelines will substantially increase these costs. The annual patient cost of receiving these services as currently practised was estimated to be US$118 and US$127 for urban and rural patients, respectively. Providers' costs were estimated from two main viewpoints: 'what is', that is the current practice, and 'what if', reflecting a WHO guidelines scenario. The higher cost of implementing the WHO guidelines suggests the need for further evaluation of whether these added costs are reasonable relative to the added benefits. We also found considerably higher patient costs, implying that distributive and equity implications of access to care require more consideration. Facility location surfaced as the main explanatory variable for both direct and indirect patient costs in the regression analysis; further research on the influence of other provider characteristics on these costs is important. PMID- 25113028 TI - An assessment of individual-level factors associated with alcohol treatment utilization among Mexican Americans. AB - The purpose of this study is to identify enabling factors for treatment utilization for alcohol-related problems, and to evaluate how enabling factors vary by need for treatment, among two samples of Mexican American adults. These two distinct samples included 2,595 current and former drinkers (one sample included 787 U.S./Mexico border residents; the other sample included 740 Mexican Americans living in U.S. cities not proximal to the border). Need for treatment (alcohol disorder severity) and (male) gender were the primary correlates of treatment utilization; and there was no moderation in the enabling factors by need for treatment as "enablers" of utilization. Further theoretical and empirical research is necessary to determine which mechanisms are driving disparities in treatment utilization across racial/ethnic groups generally, and Hispanic national groups specifically. PMID- 25113029 TI - Sac1-Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus. AB - Sac1 is a phosphoinositide phosphatase of the endoplasmic reticulum and Golgi apparatus that controls organelle membrane composition principally via regulation of phosphatidylinositol 4-phosphate signaling. We present a characterization of the structure of the N-terminal portion of yeast Sac1, containing the conserved Sac1 homology domain, in complex with Vps74, a phosphatidylinositol 4-kinase effector and the orthologue of human GOLPH3. The interface involves the N terminal subdomain of the Sac1 homology domain, within which mutations in the related Sac3/Fig4 phosphatase have been linked to Charcot-Marie-Tooth disorder CMT4J and amyotrophic lateral sclerosis. Disruption of the Sac1-Vps74 interface results in a broader distribution of phosphatidylinositol 4-phosphate within the Golgi apparatus and failure to maintain residence of a medial Golgi mannosyltransferase. The analysis prompts a revision of the membrane-docking mechanism for GOLPH3 family proteins and reveals how an effector of phosphoinositide signaling serves a dual function in signal termination. PMID- 25113030 TI - The nebulin repeat protein Lasp regulates I-band architecture and filament spacing in myofibrils. AB - Mutations in nebulin, a giant muscle protein with 185 actin-binding nebulin repeats, are the major cause of nemaline myopathy in humans. Nebulin sets actin thin filament length in sarcomeres, potentially by stabilizing thin filaments in the I-band, where nebulin and thin filaments coalign. However, the precise role of nebulin in setting thin filament length and its other functions in regulating power output are unknown. Here, we show that Lasp, the only member of the nebulin family in Drosophila melanogaster, acts at two distinct sites in the sarcomere and controls thin filament length with just two nebulin repeats. We found that Lasp localizes to the Z-disc edges to control I-band architecture and also localizes at the A-band, where it interacts with both actin and myosin to set proper filament spacing. Furthermore, introducing a single amino acid change into the two nebulin repeats of Lasp demonstrated different roles for each domain and established Lasp as a suitable system for studying nebulin repeat function. PMID- 25113032 TI - Full-length KIR3DL1*022 detected in an African donor. AB - KIR3DL1*022 is significantly different from the most common West African allele - KIR3DL1*01501. PMID- 25113033 TI - Pirfenidone for the treatment of idiopathic pulmonary fibrosis. AB - Pirfenidone is an orally administered drug with anti-fibrotic, anti-inflammatory and anti-oxidant properties. The efficacy of pirfenidone is supported by a number of Phase III trials as well as a Cochrane meta-analysis and tolerability data are also provided by clinical trials and a long-term extension phase of these studies. These trials led to the approval of pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF) in Japan in 2008 and in Europe in 2011 and it is now indicated for treatment of patients with mild-to-moderate IPF. The primary endpoint of these studies has usually been the change in percentage predicted forced vital capacity from baseline; there has been no improvement in respiratory symptoms and/or quality of life measurements and/or decrease in mortality. Clinical and basic research studies are needed to expand our knowledge, understanding the final role of pirfenidone in the treatment of IPF and also identifing genetic factors that influence the effectiveness of this treatment. PMID- 25113034 TI - Citation analysis of the most- and least-cited articles in Clinical and Experimental Ophthalmology: 2000-2013. PMID- 25113035 TI - Ethical concerns of visiting nurses caring for older people in the community. AB - BACKGROUND: An understanding of the ethical concerns encountered by visiting nurses in the community is needed. Yet, there is a lack of research on this topic. OBJECTIVES: The purpose of this study was to explore the ethical concerns that visiting nurses experience when caring for vulnerable older people living in a community. DESIGN AND SAMPLE: A qualitative thematic analysis was used to explore the nature of the ethical issues experienced by visiting nurses (N = 13) who care for vulnerable older people, over 65 years of age, in a South Korean community. METHODS: In-depth interviews were conducted with visiting nurses. Qualitative thematic analysis was used to explore the main themes of the phenomenon. ETHICAL CONSIDERATIONS: This study was approved by the Institutional Review Board of Chung-Ang University Bioethics Committee in South Korea. RESULTS: Four ethical themes emerged from the qualitative data: (a) quantitative performance rather than quality care, (b) clients being invisible, (c) tuning the level of the relationship with clients, and (d) facing the visiting nurses' own limitations. CONCLUSION: This study provides a theoretical basis to understand the ethical aspects of visiting nurses' interactions with clients, which should facilitate the development of ethical guidelines for visiting nurses to use in making ethical decisions in their practice. PMID- 25113036 TI - Is the hoopla over CPAF justified? PMID- 25113031 TI - Phosphorylated RPA recruits PALB2 to stalled DNA replication forks to facilitate fork recovery. AB - Phosphorylation of replication protein A (RPA) by Cdk2 and the checkpoint kinase ATR (ATM and Rad3 related) during replication fork stalling stabilizes the replisome, but how these modifications safeguard the fork is not understood. To address this question, we used single-molecule fiber analysis in cells expressing a phosphorylation-defective RPA2 subunit or lacking phosphatase activity toward RPA2. Deregulation of RPA phosphorylation reduced synthesis at forks both during replication stress and recovery from stress. The ability of phosphorylated RPA to stimulate fork recovery is mediated through the PALB2 tumor suppressor protein. RPA phosphorylation increased localization of PALB2 and BRCA2 to RPA-bound nuclear foci in cells experiencing replication stress. Phosphorylated RPA also stimulated recruitment of PALB2 to single-strand deoxyribonucleic acid (DNA) in a cell-free system. Expression of mutant RPA2 or loss of PALB2 expression led to significant DNA damage after replication stress, a defect accentuated by poly-ADP (adenosine diphosphate) ribose polymerase inhibitors. These data demonstrate that phosphorylated RPA recruits repair factors to stalled forks, thereby enhancing fork integrity during replication stress. PMID- 25113037 TI - Desmoplastic fibroma of the mandible: a series of three cases and review of literature. AB - The desmoplastic fibroma (DF) is a rare, fibroblastic lesion of bone that histologically resembles the desmoid tumor of soft tissue. Although classified as benign, it frequently demonstrates aggressive behavior, often causing tooth mobility, extensive bone destruction, and has a moderate to high recurrence rate. We present three cases of DF in the mandible: the first in a 13 year old female involving the mandibular body in the region of teeth #s 27-#28, the second in a 57 year old female with a lesion apical to tooth #30, and the third in a 20-year old female involving the left posterior mandible. Clinical, histologic, immunohistochemical (IHC) and radiographic features of this rare neoplasm are discussed. The challenges encountered in establishing an accurate diagnosis due to significant microscopic overlap with other spindle cell lesions are also detailed. Additionally, the findings of IHC stains including vimentin, smooth muscle actin, S-100 protein, beta-catenin, HHF-35 and proliferation marker, Ki-67 on 3 cases are reported. The potential for misdiagnosis is high, especially in early lesions, since immunohistochemistry has been reported in literature to be inconsistent when differentiating DFs from other spindle cell lesions. A comparative review of DF and similar entities in the jaws with current considerations in treatment and prognosis is presented. PMID- 25113038 TI - Dermoid cyst of the parotid gland: report of a rare entity with literature review. AB - Dermoid cysts (DCs)are benign lesions and histologically composed of tissues originating from ectoderm and mesoderm, but not endoderm. Approximately 7 % of all DCs are seen in head and neck area. However, parotid gland is an extremely rare localization in which DCs develop, and only 17 cases have been reported in the literature to date. Correct preoperative diagnosis is difficult to be established due to the rarity and ambiguous radiological findings. We report a case of a 21-year old man. All previous reports reviewed and the pathogenesis as well as the histopathologic and radiologic features are discussed. PMID- 25113039 TI - The ratio of high-density lipoprotein cholesterol to apolipoprotein A-I predicts myocardial injury following elective percutaneous coronary intervention. AB - BACKGROUND: High-density lipoprotein (HDL) has cardioprotective properties. Each HDL particle has a few molecules of apolipoprotein A-I (apoA-I) and carries various amounts of cholesterol. The ratio of high-density lipoprotein cholesterol (HDL-C) to apoA-I may reflect mean HDL particle size. HYPOTHESIS: HDL-C/apoA-I ratio may provide more information than HDL-C and apoA-I in predicting myocardial injury following elective percutaneous coronary intervention (PCI). METHODS: We prospectively enrolled 2529 consecutive patients who underwent elective PCI and assessed the relationships of preprocedural HDL-C, apoA-I, and their ratio with peak cardiac troponin I (cTnI) within 24 hours after PCI. RESULTS: Neither HDL-C nor apoA-I levels showed significant association with postprocedural cTnI elevation, whereas HDL-C/apoA-I ratio was associated with postprocedural cTnI elevation above 3 up to 30 * upper limit of normal (ULN), with the lowest risk in the middle quintile (all P values for quadratic term were <0.05). Adjusted odds ratios (95% confidence interval) of postprocedural cTnI >3 * ULN for quintile 1 to 5 of HDL-C/apoA-I ratio were: 1 (reference), 0.81 (0.62-1.07), 0.57 (0.43 0.75), 0.65 (0.49-0.85), and 0.76 (0.58-1.01), respectively, and the adjusted odds ratios of postprocedural cTnI >30 * ULN for quintile 1 to 5 of HDL-C/apoA-I ratio were: 1 (reference), 0.81 (0.49-1.361), 0.42 (0.23-0.77), 0.66 (0.38-1.14), and 0.82 (0.49-1.38), respectively. CONCLUSIONS: There was a U-shaped association between HDL-C/apoA-I ratio and myocardial injury following PCI. PMID- 25113040 TI - Gastrogastric fistulae following gastric bypass surgery-clinical recognition and treatment. AB - Gastrogastric fistula (GGF) formation is an uncommon but well-recognized complication following Roux-en-Y gastric bypass for morbid obesity. Patients with GGF may be asymptomatic or have nonspecific problems of abdominal pain, weight regain, or ulcer formation at the gastrojejunal anastomosis. Maintaining a high index of suspicion is the key to diagnosis. Flexible upper endoscopy and upper gastrointestinal fluoroscopy are complementary imaging modalities for securing the diagnosis of GGF. Surgical repair of GGF is generally the most definitive management but is invasive and has the potential for morbidity. Endoscopic methods of closure have gained favor in recent years due to their noninvasive nature despite the lack of long-term data regarding their success. Novel methods of endoscopic closure, including endoscopic suturing, more closely resemble the surgical paradigm and will likely supplant traditional surgical methods for the management of GGF. PMID- 25113041 TI - The role of endoscopy in the management of pancreatic necrosis. AB - The management of acute pancreatitis has seen many advances over the past three decades. Attempts to improve care have led to new definitions, classification systems, and treatment strategies. Despite those efforts, considerable morbidity and mortality result from complications of severe acute pancreatitis. Much attention has been given to new ways to treat these complications, including inflammatory pancreatic fluid collections and associated infections. Endoscopy has become one of the established modalities for the treatment of these complications in many expert centers. This chapter will specifically address the role of endoscopy in the management of pancreatic necrosis. PMID- 25113043 TI - Comparison of identification systems for psychrotrophic bacteria isolated from raw bovine milk. AB - Psychrotrophic bacteria in raw milk produce heat-resistant extracellular proteases, resulting in spoilage and shelf-life reduction of ultrahigh temperature treated milk and milk products. Controlling of these spoilage microbes requires rapid and reliable identification systems for screening of raw milk. This study aimed to compare commercial bacterial identification systems with a genetic method (considered as the 'gold standard' method) for the identification of heat-resistant protease producing bacteria in raw milk. Five bacterial identification systems were compared based on typability, discrimination power (i.e. Simpson's Index of Diversity), reproducibility and speed of analysis. The accuracy of 16S rRNA gene sequencing, Biolog, MALDI-TOF MS, API, and Microbact for the identification of Gram negative bacilli at the species level was 100.0%, 86.8%, 63.2%, 60.5% and 57.9%, respectively. The Gram positive bacilli were identified by 16S rRNA gene sequencing, Biolog, MALDI-TOF MS, and API with accuracies at the species level of 100.0%, 85.0%, 95.0% and 90.0%, respectively. The 16S rRNA gene sequencing and phylogenetic analysis discriminated Pseudomonas fluorescens, Pseudomonas syringae, Hafnia alvei, Bacillus cereus, Bacillus pumilus and Bacillus licheniformis to the subspecies level. The Simpson's Index of Diversity scores were 0.966, 0.711, 0.496, 0.472, and 0.140, for 16S rRNA gene sequencing, Biolog, MALDI-TOF MS, API and Microbact, respectively. Limited reference profiles in the databases of Biolog, MALDI-TOF MS, API and Microbact systems reduced their accuracy in bacterial identification, compared to 16S rRNA gene sequencing. The rapidity of each assay is in the following order; MALDI-TOF MS>16S rRNA gene sequencing>Biolog>Microbact>API. The reproducibility of the assays is in the order of 16S rRNA gene sequencing>API>Microbact>MALDI-TOF MS>Biolog. Thus, 16S rRNA gene sequencing appears to be the most reliable and robust system for the identification of dairy spoilage bacteria. The Biolog system is suitable for the identification of Gram negative spoilage bacteria, while MALDI-TOF MS and API systems are suitable for the identification of Gram positive spoilage bacteria isolated from raw milk. The commercial systems used in this study have been developed and extensively used for the identification of clinical microbes but only a limited number of studies used those systems to identify the environmental microorganisms that often contaminate raw milk. Therefore, comparison of those systems for the identification of spoilage microbes in raw milk would provide better understanding of their suitability for routine dairy microbiology and more extensive dairy research. PMID- 25113042 TI - Chromoendoscopy for colorectal cancer surveillance in patients with inflammatory bowel disease. AB - Chromoendoscopy utilizes colorimetric techniques to increase detection of lesions that are difficult to see or cannot be seen with conventional white light endoscopy. Multiple studies have demonstrated that chromoendoscopy with dye spraying significantly increases the detection of dysplastic lesions in patients with chronic inflammatory bowel disease (IBD) of the colon undergoing colonoscopy. Furthermore, chromoendoscopy may obviate the need for random biopsies and pending additional studies and may allow increased intervals between surveillance exams, reducing costs while increasing the sensitivity for detection of dysplasia per exam. Despite convincing data supporting the use of chromoendoscopy for IBD colonic surveillance, it is seldom utilized outside of academic centers. Here, we review the current approach to colorectal cancer surveillance in IBD focusing on the data supporting the use of chromoendoscopy including its use in a community setting and offer practical recommendations for incorporating chromoendoscopy as a routine part of surveillance in IBD regardless of practice setting. PMID- 25113044 TI - Characterization of integrons and resistance genes in multidrug-resistant Salmonella enterica isolated from meat and dairy products in Egypt. AB - Foodborne pathogens are a leading cause of illness and death, especially in developing countries. The problem is exacerbated if bacteria attain multidrug resistance. Little is currently known about the extent of antibiotic resistance in foodborne pathogens and the molecular mechanisms underlying this resistance in Africa. Therefore, the current study was carried out to characterize, at the molecular level, the mechanism of multidrug resistance in Salmonella enterica isolated from 1600 food samples (800 meat products and 800 dairy products) collected from different street venders, butchers, retail markets and slaughterhouses in Egypt. Forty-seven out of 69 isolates (68.1%) showed multidrug resistance phenotypes to at least three classes of antimicrobials. The incidence of multidrug-resistant isolates was higher in meat products (37, 69.8%) than in dairy products (10, 62.5%). The multidrug-resistant serovars included, S. enterica serovar Typhimurium (24 isolates, 34.8%), S. enterica serovar Enteritidis, (15 isolates, 21.8%), S. enterica serovar Infantis (7 isolates, 10.1%) and S. enterica non-typable serovar (1 isolate, 1.4%). The highest resistance was to ampicillin (95.7%), then to kanamycin (93.6%), spectinomycin (93.6%), streptomycin (91.5%) and sulfamethoxazole/trimethoprim (91.5%). PCR and DNA sequencing were used to screen and characterize integrons and antibiotic resistance genes and 39.1% and 8.7% of isolates were positive for class 1 and class 2 integrons, respectively. beta-lactamase-encoding genes were identified in 75.4% of isolates and plasmid-mediated quinolone resistance genes were identified in 27.5% of isolates. Finally, the florphenicol resistance gene, floR, was identified in 18.8% of isolates. PCR screening identified S. enterica serovar Typhimurium DT104 in both meat and dairy products. This is the first study to report many of these resistance genes in dairy products. This study highlights the high incidence of multidrug-resistant S. enterica in meat and dairy products in Egypt, with the possibility of their transfer to humans leading to therapeutic failure. Therefore, the overuse of antibiotics in animals should be drastically reduced in developing countries. PMID- 25113045 TI - Biocontrol activity of four non- and low-fermenting yeast strains against Aspergillus carbonarius and their ability to remove ochratoxin A from grape juice. AB - Aspergillus spp. infection of grape may lead to ochratoxin A (OTA) contamination in processed beverages such as wine and grape juice. The aim of the current study was to evaluate the biocontrol potential of two non-fermenting (Cyberlindnera jadinii 273 and Candida friedrichii 778) and two low-fermenting (Candida intermedia 235 and Lachancea thermotolerans 751) yeast strains against the pathogenic fungus and OTA-producer Aspergillus carbonarius, and their ability to remove OTA from grape juice. Two strains, 235 and 751, showed a significant ability to inhibit A. carbonarius both on grape berries and in in vitro experiments. Neither their filtrate nor their autoclaved filtrate culture broth was able to prevent consistently pathogen growth. Volatile organic compounds (VOCs) produced by all four selected yeasts were likely able to consistently prevent pathogen sporulation in vitro. VOCs produced by the non-fermenting strain 778 also significantly reduced A. carbonarius vegetative growth. Three yeast strains (235, 751, and 778) efficiently adsorbed artificially spiked OTA from grape juice, while autoclaving treatment improved OTA adsorption capacity by all the four tested strains. Biological control of A. carbonarius and OTA decontamination using yeast is proposed as an approach to meet the Islamic dietary laws concerning the absence of alcohol in halal beverages. PMID- 25113046 TI - Synthesis and in vitro pharmacological evaluation of novel 2-hydroxypropyl-4 arylpiperazine derivatives as serotoninergic ligands. AB - This paper reports the synthesis of new norbornene and exo-N-hydroxy-7 oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboximide derivatives and their binding to the 5-HT1A , 5-HT2A , and 5-HT2C receptors, in order to identify selective ligands for these 5-hydroxytryptamine (5-HT, serotonine) receptor subtypes. The combination of structural elements (heterocyclic nucleus, hydroxyalkyl chain, and 4-substituted piperazine) known to be critical for affinity to 5-HT1A receptors and the proper selection of substituents led to compounds with high specificity and affinity toward serotoninergic receptors. The most active compounds were selected and further evaluated for their binding affinities to D1 , D2 dopaminergic and alpha1 , alpha2 adrenergic receptors. 4-[3-[4-(2 Furoyl)piperazin-1-yl]propoxy-2-ol]-4-aza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione 3e with Ki = 5.04 +/- 0.227 nM was the most active and selective derivative for the 5-HT2C receptor with respect to other serotonin receptors, and the most selective derivative versus dopaminergic and adrenergic receptors. PMID- 25113047 TI - Interobserver and intraobserver repeatability of lipid layer pattern evaluation by two experienced observers. AB - PURPOSE: The lipid layer plays a major role in limiting evaporation of the tear film. Based on interference phenomena, there is a test directed to lipid layer pattern (LLP) evaluation, but is affected by subjective interpretation of the patterns. The aim of this study is to compare the LLP evaluation between two experienced observers on a group of healthy patients. Furthermore, observers re evaluated the same images to check their individual repeatability. MATERIALS AND METHODS: LLP was examined using a Tearscope-plus (Keeler, Windsor, UK) attached to a slit lamp. Tear film was recorded by a Topcon DV-3 digital camera video and LLP images were captured. This yielded 124 LLP images that were categorized (based on Guillon's scheme) by two expert observers in two sessions separated by one month. Interobserver repeatability and intraobserver repeatability between both sessions were studied by using Cohen's kappa coefficient. RESULTS: Comparing LLP categorization between both observers, Cohen's kappa coefficient was 0.615 and 0.633 for first and second session, respectively. When comparing LLP categorization by the same observer between both sessions, Cohen's kappa coefficient was 0.770 and 0.812 for Observer 1 and Observer 2, respectively. These results indicate substantial correlation in all cases. The most frequent misinterpretations were between open and closed meshwork and Wave and closed meshwork patterns. CONCLUSION: Although substantial correlation was found between categorizations of experienced observers, misinterpretation of the patterns may appear even in the same observer. Some misinterpretations between adjacent patterns could be palliated by including intermediate patterns between those categories. PMID- 25113048 TI - An imprinted Ag@CdS core shell nanoparticle based optical-electrochemical dual probe for trace level recognition of ferritin. AB - In this work, we present a new approach to prepare the Ag@CdS core-shell fluorescent nanoparticles wrapped with molecularly imprinted polymer for ferritin macromolecule by capping with vinyl derivative of cysteine. The imprinted Ag@CdS nanoparticle was prepared via activator regenerated by electron transfer-atom transfer radical polymerization (ARGET-ATRP) method onto the surface of vinyl silane modified pencil graphite electrode. Combination of Ag and CdS in a single motif causes the dual behavior of core shell nanoparticle, which shows enhanced fluorescence as well as electrochemical properties. The performance of the obtained imprinted sensor was investigated by cyclic voltammetry, electrochemical impedance spectroscopy, chronocoulometry, differential pulse voltammetry and fluorescence spectrophotometry. Under the optimal experimental conditions, the current response of the electrochemical sensor was linear to ferritin concentrations in the range from 1.99 to 23.43 ug L-1, with the detection limit of 0.65 ug L-1. Similarly, a linear response was obtained between fluorescence quenching of imprinted Ag@CdS and concentration of ferritin in the range from 4.0 to 91.0 ug L-1, with limit of detection (LOD) of 1.3 ug L-1. The method was successfully applied to the analysis of blood serum samples of five different men and women with acceptable recoveries of 99.7% and 100.3% (RSD in %=1.0-2.0). PMID- 25113049 TI - An exonuclease I-based label-free fluorometric aptasensor for adenosine triphosphate (ATP) detection with a wide concentration range. AB - A novel aptamer-based label-free assay for sensitive and selective detection of ATP was developed. This assay employs a new aptamer/fluorescent probe system that shows resistance to exonuclease I (Exo I) digestion upon binding to ATP molecules. In the absence of ATP, the complex between the ATP-binding aptamer (ATP-aptamer) and a DNA binding dye, berberine, is digested upon the addition of exonuclease I, leading to the release of berberine into solution and consequently, quenched berberine fluorescence. In the presence of ATP, the ATP binding aptamer folds into a G-quadruplex structure that is resistant to Exo I digestion. Accordingly, berberine is protected in the G-quadruplex structure and high fluorescence intensity is observed. As such, based on the fluorescence signal change, a label-free fluorescence assay for ATP was developed. Factors affecting the analysis of ATP including the concentration of ATP-binding aptamer, reaction time, temperature and the concentration of Exo I were comprehensively investigated. Under optimal conditions, the fluorescence intensity of the sensing system displayed a response for ATP in a wide range up to 17.5 mM with a detection limit of 140 nM. PMID- 25113050 TI - Using poly(3-aminophenylboronic acid) thin film with binding-induced ion flux blocking for amperometric detection of hemoglobin A1c. AB - This study reports a novel enzyme-free, label-free amperometric method for direct detection of hemoglobin A1c (Hb(A1c)), a potent biomarker for diabetes diagnosis and prognosis. The method relies on an electrode modified with poly(3 aminophenylboronic acid) (PAPBA) nanoparticles (20-50 nm) and a sensing scheme named "binding-induced ion flux blocking." The PAPBA nanoparticles were characterized by FT-IR, XPS, TEM, and SEM. Being a polyaniline derivative, PAPBA showed an ion-dependent redox behavior, in which insertion or extraction of ions into or out of PABPA occurred for charge balance during the electron transfer process. The polymer allowed Hb(A1c) selectively bound to its surface via forming the cis-diol linkage between the boronic acid and sugar moieties. Voltammetric analyses showed that Hb(A1c) binding decreased the redox current of PAPBA; however, the binding did not alter the redox potentials and the apparent diffusivities of ions. This suggests that the redox current of PAPBA decreased due to an Hb(A1c) binding-induced ion flux blocking mechanism, which was then verified and characterized through an in situ electrochemical quartz crystal microbalance (EQCM) study. Assay with Hb(A1c) by differential pulse voltammetry (DPV) indicates that the peak current of a PAPBA electrode has a linear dependence on the logarithm of Hb(A1c) concentration ranging from 0.975 to 156 MUM. The Hb(A1c) assay also showed high selectivity against ascorbic acid, dopamine, uric acid, glucose and bovine serum albumin. This study has demonstrated a new method for developing an electrochemical Hb(A1c) biosensor and can be extended to other label-free, indicator-free protein biosensors based on a similar redox polymer electrode. PMID- 25113051 TI - Synthesis of carbon nanotube-nickel nanocomposites using atomic layer deposition for high-performance non-enzymatic glucose sensing. AB - A useful strategy has been developed to fabricate carbon-nanotube-nickel (CNT-Ni) nanocomposites through atomic layer deposition (ALD) of Ni and chemical vapor deposition (CVD) of functionalized CNTs. Various techniques, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), were used to characterize the morphology and the structure of as-prepared samples. It was confirmed that the products possess uniform Ni nanoparticles that are constructed by finely controlled deposition of Ni onto oxygen or bromine functionalized CNT surface. Electrochemical studies indicate that the CNT-Ni nanocomposites exhibit high electrocatalytic activity for glucose oxidation in alkaline solutions, which enables the products to be used in enzyme-free electrochemical sensors for glucose determination. It was demonstrated that the CNT-Ni nanocomposite-based glucose biosensor offers a variety of merits, such as a wide linear response window for glucose concentrations of 5 MUM-2 mM, short response time (3 s), a low detection limit (2 MUM), high sensitivity (1384.1 MUA mM(-1) cm(-2)), and good selectivity and repeatability. PMID- 25113052 TI - A highly sensitive non-enzymatic glucose sensor based on bimetallic Cu-Ag superstructures. AB - Bimetallic Cu-Ag superstructures were successfully fabricated for the first time by using the natural leaves as reducing agent through a facile one-step hydrothermal process. Morphology, structure and composition of the Cu-Ag superstructures were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectra (XPS) and inductively coupled plasma-optical emission spectroscopy (ICP-OES), respectively. The results reveal that the Cu-Ag superstructure is bimetallic nanocomposite constructed by nanoparticles with low Ag content and shows a rough surface and porous flexural algae-like microstructure. By using a three-dimensional nickel foam as the scaffold, a novel non-enzymatic glucose sensor based on Cu-Ag nanocomposites has been fabricated and applied to non-enzymatic glucose detection. The as-prepared Cu-Ag nanocomposites based glucose sensor displays distinctly enhanced electrocatalytic activity compared to those obtained with pure Cu nanomaterials prepared with a similar procedure, revealing a synergistic effect of the matrix Cu and the doped Ag. Cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy indicate that the Cu-Ag superstructures based glucose sensor displays a fascinating sensitivity up to 7745.7 MUA mM(-1) cm(-2), outstanding detection limit of 0.08 MUM and fast amperometric response (<2 s) for glucose detection. Furthermore, the sensor also exhibits significant selectivity, excellent stability and reproducibility, as well as attractive feasibility for real sample analysis. Because of its excellent electrochemical performance, low cost and easy preparation, this novel electrode material is a promising candidate in the development of non-enzymatic glucose sensor. PMID- 25113054 TI - Temperament and character as determinants of well-being. AB - OBJECTIVES: We aimed to evaluate the effects of Temperament and Character Inventory (TCI) personality measures on well-being scores in a sample of 49-51 year old New Zealanders. Previous research has linked high self-directedness (SD) and low harm avoidance (HA) with well-being. We hypothesised that SD and HA would have predictive power for Warwick-Edinburgh Mental Well-being Scale (WEMWBS) well being. We anticipated that character profiles with high SD and cooperativeness (CO) would be associated with higher well-being scores while high self transcendence (ST) scores would have less of an influence on well-being in a secular population such as New Zealand. Additionally we aimed to describe and assess the performance of a well-being measure, the WEMWBS and we intended to clarify the factors that underlie the questionnaire. METHODS: A cohort of 404 randomly selected participants in a study of ageing had WEMWBS means calculated and with principal component analysis used to investigate the factors that underlie the WEMWBS. Multiple hierarchical regression was used to predict WEMWBS scores from socio-demographic and TCI personality variables. ANOVA were used to explore the non-linear effects of personality profiles on well-being. RESULTS: Principal components analysis revealed one significant factor which explained 54.34% of the variance. After initial univariate analysis current depression, marital status and standard of living were entered at the first step of the multivariate regression. They explained 20% of the variance. In step two the seven TCI personality variables were added to the model, explaining a total of 49% (R(2) change=0.29). Low HA, high SD and the absence of current depression were the main predictors of WEMWBS scores. Character profiles featuring high SD produced significantly higher scores on the WEMWBS. Total WEMWBS scores were normally distributed, and the mean was 52.83 (95% CI 51.96-53.70). CONCLUSIONS: The key determinants of well-being were absence of current depression and personality variables, especially low HA and high SD. The WEMWBS has face validity and the New Zealand results were very similar to the UK results. PMID- 25113053 TI - Piezoresistive microcantilever-based DNA sensor for sensitive detection of pathogenic Vibrio cholerae O1 in food sample. AB - Pathogenic Vibrio cholerae produces a cholera toxin which is the cause of a severe diarrheal disease called "Cholera". Available detection methods, including standard bacteriological test and immuno-based detection, are specific to the suspected pathogenic V. cholerae O1 and O139, but they are not specific to the cholera toxin producible strain. This work combined the polymerase chain reaction (PCR) of cholera toxin gene, ctxA gene, and microcantilever-based DNA sensor to improve the sensitivity and specificity of detection. Gold coated microcantilever, 250 um long and 50 um wide, with an embedded polysilicon wire acting as a piezoresistive material was modified by a self-assembled monolayer (SAM) of 3-mercaptopropionic acid (MPA) for immobilization of specific DNA probe via avidin layer on the surface. The avidin and 5' biotinylated single-stranded DNA (ssDNA) probe concentrations were optimized for the immobilization at 50 ug/mL and 1 uM, respectively. The hybridization between ssDNA probe on this DNA sensor and target DNA creates nanomechanical bending and resistance change of piezoresistive material inside the beam. This microcantilever-based DNA sensor offers a detection sensitivity of 3.25 pg or 14 nM of DNA template for ctxA gene detection. The lowest number of V. cholerae O1 in food sample with and without the enrichment process that the polymerase chain reaction (PCR) for ctxA gene combined with this DNA sensor can detect is 0.835 and 835 cells/g, respectively. This detection sensitivity is 10 times higher than that of the conventional PCR method. PMID- 25113055 TI - Losing control: assaultive behavior as a predictor of impulse control disorders in young adults. AB - OBJECTIVE: Assaultive behaviors are common among young people and have been associated with a range of other unhealthy, impulsive behaviors such as substance use and problem gambling. This study sought to determine the predictive ability of single assaultive incidents for impulse control disorders, an association that has yet to be examined, especially in young adults. METHODS: The authors conducted a university-wide email survey in the spring of 2011 on 6000 university students. The survey examined assaultive behavior and associated mental health variables (using a clinically validated screening instrument, the Minnesota Impulsive Disorders Interview), stress and mood states, and psychosocial functioning. RESULTS: The rate of response was 35.1% (n=2108). 109 (5.9%) participants reported that they had assaulted another person or destroyed property at some time in their lives. Compared with respondents without lifetime assaultive behavior, those with a history of assaultive or destructive behavior reported more depressive symptoms, more stress, and higher rates of a range of impulse control disorders (intermittent explosive disorder, compulsive sexual behavior, compulsive buying, and skin picking disorder). CONCLUSIONS: Assaultive behavior appears fairly common among college students and is associated with symptoms of depression and impulse control disorders. Significant distress and diminished behavioral control suggest that assaultive behaviors may often be associated with significant morbidity. Additional research is needed to develop specific prevention and treatment strategies for young adults attending college who report problems with assaultive behaviors. PMID- 25113056 TI - A preliminary investigation of the long-term outcome of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders. AB - OBJECTIVE: The aim of this study is to conduct a preliminary examination of long term outcomes on a broad range of affective disorder symptoms treated with a newly developed intervention: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP). METHOD: Maintenance of treatment gains at long-term follow-up (LTFU) were explored in patients (N=15, mean age=32.27; 60% female) who completed a clinical trial of the UP. RESULTS: Treatment gains observed at 6 month follow-up (6MFU) on measures of clinical severity, general symptoms of depression and anxiety, and a measure of symptom interference in daily functioning were largely maintained 12months later (at an average of 18months posttreatment), and any significant changes from 6MFU to LTFU reflected small increases in symptoms that remained, on average, in the subclinical range. CONCLUSIONS: These findings provide the first initial support for the durability of broad treatment gains following transdiagnostic treatment. PMID- 25113057 TI - Spread of carbapenemase-producing enterobacteria in a southwest hospital in China. AB - BACKGROUND: The rapid emergence and dissemination of carbapenem resistance in Enterobacteriaceae complicates the treatment of infections caused by these organisms. METHODS: We collected clinical isolates with meropenem inhibition zones of <= 22 mm from January 1, 2009, through December 31, 2010. We attempted to amplify the NDM-1 gene from these isolates and conducted the modified Hodge test (MHT). The minimal inhibitory concentration (MIC) of the MHT-positive strains was determined by the agar disk dilution method. The carbapenemase encoding resistance genes of these strains were examined using polymerase chain reaction (PCR) analysis and a sequencing strategy to characterize these enzymes. The clonal relationship among isolates was analyzed by pulsed-field gel electrophoresis (PFGE). RESULTS: Among the 158 Enterobacteriaceae isolates that were collected, there were no NDM-1-positive strains and 26 MHT-positive strains. Among the latter, 18 strains were IMP-4-positive, and 1 was KPC-2-positive. In addition, 15 of the IMP-4-positive Klebsiella pneumoniae strains belonged to 4 PFGE genotypes, with 8 strains having the same genotype. CONCLUSION: These results suggest that nosocomial infections are one of the main reasons for the spread of these resistant strains. PMID- 25113058 TI - Caspase-3 inhibition prevents the development of hepatopulmonary syndrome in common bile duct ligation rats by alleviating pulmonary injury. AB - BACKGROUND & AIMS: Common bile duct ligation (CBDL) rats is an accepted experimental model of hepatopulmonary syndrome (HPS), defined as liver disease and intrapulmonary vascular dilatation and hypoxaemia. Pulmonary Akt and ERK activation followed by angiogenesis in the later stages of CBDL, contribute to the pathogenesis of HPS. However, the mechanisms behind Akt and ERK activation remain undefined. Pulmonary injury induced by increased bilirubin, endotoxin and inflammatory mediators occurs in the early stages of CBDL. We assessed the effects of relieving pulmonary injury on Akt and ERK activation and on the development of HPS following CBDL. METHODS: Pulmonary injury, angiogenesis, arterial oxygenation, cell proliferation and, phospho-Akt and ERK1 were evaluated in CBDL animals with or without caspase-3 inhibition (Z-DEVD-FMK). Pulmonary injury was assessed by histology and quantifying apoptosis and aquaporin-1 (AQP1) levels. Lung angiogenesis was assessed by quantifying AQP1 level, vWF-positive cells and microvessel count. RESULTS: Pulmonary apoptosis and caspase-3 activation were markedly increased in the early stages of CBDL. Caspase-3 inhibition alleviated apoptosis, the reduction in AQP1, phospho-Akt and ERK1 levels and pulmonary injury 1 week after CBDL. Caspase-3 inhibition also reduced AQP1, phospho-Akt and ERK1 levels, vWF-positive cells, cell proliferation, microvessel count, and microvascular dilatation and improved arterial oxygenation 3 weeks following CBDL. CONCLUSIONS: Caspase-3 inhibition alleviates pulmonary injury, thereby preventing angiogenesis as well as the development of HPS in CBDL rats. These effects are related to the regulation of the Akt and ERK1 pathways. PMID- 25113060 TI - In vivo gastric detection of alpha-synuclein inclusions in Parkinson's disease. AB - alpha-Synuclein inclusions have been identified in the brain and some parts of the enteric nervous system in Parkinson's disease cases. We aimed to assess these inclusions in gastric mucosa samples from patients with symptomatic Parkinson's disease. Random biopsies were performed by gastroscopy in 28 patients with Parkinson's disease and in 29 age- and sex-matched controls. Gastroscopy was performed to start enteral levodopa (L-dopa) therapy in cases and for diagnostic purposes in controls (gastroesophageal reflux, anemia, and abdominal pain were the main indications). The clinical definition of cases and controls was made a priori. Six controls had data suggestive of "mild presymptomatic parkinsonism". Biopsy specimens were immunostained for alpha-synuclein. The neuropathological diagnosis was established post hoc. No differences were found in the baseline characteristics of the groups. Positive fibers for the alpha-synuclein protein were observed in 17 of 28 (60.7%) Parkinson's disease patients, 1 of 23 controls (4.3%), and 1 of 6 (16.7%) cases of incident "mild presymptomatic parkinsonism." Neuropathological diagnosis based on alpha-synuclein immunostaining showed a sensitivity of 85% (95% confidence interval [CI] 62.1-96.8), specificity of 95% (95% CI 76.2-99.9) and area under the receiver operating characteristics curve (AUC) of 0.90 (95% CI 0.80-1.00). No adverse events occurred. Detection of alpha synuclein inclusions in the gastric mucosa is a useful and safe tool providing in vivo evidence of the underlying neurodegenerative peripheral involvement linked to Parkinson's disease. Further studies are warranted to determine its pathophysiological implications. PMID- 25113062 TI - Reactions of atomic hydrogen with formic acid and carbon monoxide in solid parahydrogen II: Deuterated reaction studies. AB - It is difficult to determine whether the measured rate constant for reaction of atomic hydrogen with formic acid reported in Part 1 reflects the H atom quantum diffusion rate or the rate constant for the tunneling reaction step. In Part 2 of this series, we present kinetic studies of the postphotolysis H atom reactions with deuterated formic acid (DCOOD) to address this ambiguity. Short duration 193 nm in situ photolysis of DCOOD trapped in solid parahydrogen results in partial depletion of the DCOOD precursor and photoproduction of primarily CO, CO2, DOCO, HCO and mobile H atoms. At 1.9 K we observe post-irradiation growth in the concentrations of DOCO and HCO that can be explained by H atom tunneling reactions with DCOOD and CO, respectively. Conducting experiments with different deuterium isotopomers of formic acid (DCOOD, DCOOH, HCOOD and HCOOH) provides strong circumstantial evidence the reaction involves H atom abstraction from the alkyl group of formic acid. Further, the anomalous temperature dependence measured for the H + HCOOH reaction in Part 1 is also observed for the analogous reactions with deuterated formic acid. The rate constants extracted for H atom reactions with DCOOD and HCOOH are equivalent to within experimental uncertainty. This lack of a kinetic isotope effect in the measured rate constant is interpreted as evidence the reactions are diffusion limited; the measured rate constant reflects the H atom diffusion rate and not the tunneling reaction rate. Whether or not H atom reactions with chemical species in solid parahydrogen are diffusion limited is one of the outstanding questions in this field, and this work makes significant strides toward showing the reaction kinetics with formic acid are diffusion limited. PMID- 25113061 TI - Cellular inhibitors of apoptosis (cIAP) 1 and 2 are increased in placenta from obese pregnant women. AB - INTRODUCTION: Independent of their role in apoptosis, cellular inhibitors of apoptosis (cIAP) 1 and 2, have emerged as regulators of inflammation. Obesity in pregnancy is characterised by maternal and placental inflammation. Thus, the aim of this study was to determine the effect of maternal obesity and pro inflammatory mediators on cIAP expression in human placenta. METHODS: The expression of cIAP was assessed in human placenta from lean (n = 15) and obese (n = 14) patients by qRT-PCR and Western blotting. Primary trophoblast cells were used to determine the effect of pro-inflammatory cytokines on cIAP expression, and the effect of cIAP siRNA on pro-inflammatory cytokines. RESULTS: cIAP1 and cIAP2, gene and protein expression were significantly higher in placenta from women with pre-existing maternal obesity compared to placenta form lean women. Additionally, bacterial endotoxin LPS and the pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta significantly increased the expression of both cIAP1 and cIAP2 in primary trophoblast cells isolated from human term placenta. Knockdown of cIAP1 or cIAP2 in human primary trophoblast cells significantly decreased TNF-alpha induced expression and secretion of pro inflammatory cytokines IL-6 and IL-8 and of matrix metalloproteinase (MMP)-9. DISCUSSION: cIAP1 and cIAP2 expression is increased in placenta from women with pre-existing maternal obesity and in response to treatment with pro-inflammatory cytokines. Functional studies in placental trophoblast cells revealed that cIAPs are involved in TNF-alpha induced-expression of pro-inflammatory cytokines. Given the central role of pro-inflammatory cytokines in placental nutrient transport, this data suggest that cIAP1 and cIAP2 may play a role in fetal growth and development. PMID- 25113059 TI - Whole genome RNAi screens reveal a critical role of REV3 in coping with replication stress. AB - REV3, the catalytic subunit of translesion polymerase zeta (polzeta), is commonly associated with DNA damage bypass and repair. Despite sharing accessory subunits with replicative polymerase delta, very little is known about the role of polzeta in DNA replication. We previously demonstrated that inhibition of REV3 expression induces persistent DNA damage and growth arrest in cancer cells. To reveal determinants of this sensitivity and obtain insights into the cellular function of REV3, we performed whole human genome RNAi library screens aimed at identification of synthetic lethal interactions with REV3 in A549 lung cancer cells. The top confirmed hit was RRM1, the large subunit of ribonucleotide reductase (RNR), a critical enzyme of de novo nucleotide synthesis. Treatment with the RNR-inhibitor hydroxyurea (HU) synergistically increased the fraction of REV3-deficient cells containing single stranded DNA (ssDNA) as indicated by an increase in replication protein A (RPA). However, this increase was not accompanied by accumulation of the DNA damage marker gammaH2AX suggesting a role of REV3 in counteracting HU-induced replication stress (RS). Consistent with a role of REV3 in DNA replication, increased RPA staining was confined to HU treated S-phase cells. Additionally, we found genes related to RS to be significantly enriched among the top hits of the synthetic sickness/lethality (SSL) screen further corroborating the importance of REV3 for DNA replication under conditions of RS. PMID- 25113063 TI - Changes in length of the plantar aponeurosis during the stance phase of gait--an in vivo dynamic fluoroscopic study. AB - In locomotion, ligaments and muscles have been recognized to support the arch of the foot. However, it remains unclear to what extent the passive and active structures of the lower extremity support the longitudinal arch of the foot during walking. In this study, the mechanical function of the plantar aponeurosis (PA) is investigated by elongation measurements in vivo during the stance phase of gait, in combination with measurements of the mechanical properties of the PA in vitro. Fluoroscopy was used to measure the dynamic changes in PA length and the angular motion of the metatarsophalangeal joint of the first ray, measured during the stance phase (StPh) in 11 feet. Simultaneously, ground forces were measured. Additionally, four cadaver feet delivered topographic information relating to the PA, and three autopsy specimens of PA served to determine the in vitro mechanical properties of PA. The present study revealed a non-significant peak average PA shortening of 0.48% at about 32.5% StPh, followed by a significant average peak elongation of 3.6% at 77.5% StPh. This average peak elongation of 3.6% corresponds to a force of 292N, as estimated by mechanical testing of the autopsy PA specimens. Considering the maximum peak elongation measured in one volunteer of 4.8% at 76% StPh, a peak PA load of 488N might be expected. Hence, with an average body weight of 751N, as allocated to the 11 investigated feet, this maximum peak force would correspond to about 0.65*body weight. As far as we are aware, this is the first report on a dynamic fluoroscopic study of the PA in gait with an appreciable number of feet (11 feet). In conclusion, muscles contribute to support of the longitudinal arch of the foot and can possibly relax the PA during gait. The 'windlass effect' for support of the arch in this context is therefore questionable. PMID- 25113065 TI - Thromboembolic incidence with transiently elevated levels of coagulation factors in patients with von Willebrand disease treated with VWF:FVIII concentrate during surgery. PMID- 25113066 TI - Somatic mosaicism for the COL7A1 mutation p.Gly2034Arg in the unaffected mother of a patient with dystrophic epidermolysis bullosa pruriginosa. AB - Dystrophic epidermolysis bullosa (DEB) is a heritable blistering disorder caused by mutations in the type VII collagen gene, COL7A1. Although revertant mosaicism is well known in DEB, 'forward' somatic mosaicism, in which a pathogenic mutation arises on a wild-type (WT) background, extending beyond the germ cells, has not been reported. It is therefore unknown what proportion of sporadic dominant DEB (DDEB) cases result from de novo mutations or somatic mosaic parents. In the clinically unaffected mother of a patient with DDEB pruriginosa due to the p.Gly2034Arg mutation, we identified the p.Gly2034Arg mutation in a proportion of lymphocytes and skin cells (mutational load 10-25%). Our data emphasize that forward mosaicism occurs in DDEB and highlight that mutation analysis should always be performed in the parents of sporadic DDEB patients to confirm the de novo status of the mutation. Ultimately, this will reveal the frequency of true de novo mutations and somatic mosaicism in parents, which has important implications for genetic counselling. Our data indicate that the threshold of mutant type VII procollagen to develop DDEB must be higher than 10-25%, which provides a rationale for therapeutic approaches aimed at increasing the WT : mutant type VII collagen ratio. PMID- 25113067 TI - Parathyroid hormone may be an early predictor of low serum hemoglobin concentration in patients with not advanced stages of chronic kidney disease. AB - BACKGROUND: Parathyroid hormone (PTH) has been associated with anemia only in dialysis patients with severe hyperparathyroidism. Whether an association between PTH and hemoglobin also exists in patients with chronic kidney disease not on dialysis (CKD-patients) is still unclear. In this study we evaluated the association between PTH and hemoglobin in CKD-patients without severe secondary hyperparathyroidism. METHODS: Hospitalized patients and outpatients (N = 979) were retrospectively evaluated and categorized according to PTH quartile and serum hemoglobin (<12.0, <11.0, <10.0 g/dl). Gender, diabetes, glomerular filtration rate (GFR), hemoglobin, PTH, markers of mineral metabolism, inflammation, iron status and nutrition were variables of adjustment in univariate and multivariate analysis. RESULTS: An inverse association (p = 0.001) was observed between PTH and hemoglobin in patients as a whole, in diabetics, and in patients with GFR <=60 ml/min. PTH was the single predictor of low hemoglobin in patients as a whole (unstandardized beta -2.12; p = 0.005), in diabetics (unstandardized beta -8.86; p = 0.007) and in patients with GFR <=60 ml/min (unstandardized beta -2.52; p = 0.006). For each increase of quartile of PTH the risk of having hemoglobin level <10.0 mg/dl was more than doubled [hazard ratio (HR) 2.79, 95% confidence interval (CI) 2.00-3.88; p = 0.001]. The receiver operating characteristic curve showed that PTH >=122 pg/ml had 67% sensitivity and 75% specificity in predicting hemoglobin level <10.0 g/dl with area under the curve of 0.758 (95% CI 0.73-0.78). CONCLUSIONS: This study shows a significant inverse association between PTH and hemoglobin levels across the whole spectrum of non-dialysis CKD and a doubled risk of having serum hemoglobin <10.0 mg/dl in the absence of severely deranged PTH concentration. These findings may have clinical relevance in ascertaining the cause of unexplained low hemoglobin levels in CKD-patients. PMID- 25113068 TI - Applicability of the Chinese version of the 16-item Prodromal Questionnaire (CPQ 16) for identifying attenuated psychosis syndrome in a college population. AB - AIM: The aim of this study was to examine the reliability, validity, sensitivity and specificity of the Chinese version of the 16-item Prodromal Questionnaire (CPQ-16) for identifying attenuated psychosis syndrome (APS) in a college population. METHODS: The participants were recruited from a university. Five hundred seventy-nine students completed the CPQ-16 and the Symptom Checklist-90. One class (n = 79) was randomly selected to be retested with the CPQ-16 after 2 weeks. A randomly selected group of 49 individuals who tested positive and 50 individuals who tested negative were interviewed using the Structured Interview for Prodromal Syndromes (SIPS). RESULTS: The internal consistency reliability was good (Cronbach's alpha = 0.72). The test-retest reliability was 0.88. The total score on the CPQ-16 was moderately to highly correlated with the total score on the Symptom Checklist-90 and all of the subscales (r = 0.39-0.67, P < 0.001). A cut-off CPQ-16 score of 9 was used to differentiate between those with a APS diagnosis on the SIPS versus those with no SIPS diagnoses; this cut-off value yielded 85% sensitivity, 87% specificity, a positive predictive value of 63% and a positive likelihood ratio of 6.69. The area under the ROC curve (AUC) was significant for the CPQ-16 total score (AUC = 0.93, SE = 0.026, 95% CI = 0.87 0.98, P < 0.001). Based on the proposed cut-off score, the CPQ-16 yielded a positive rate of 5.0% (29/579). CONCLUSIONS: The CPQ-16, administered in a face to-face interview, demonstrated high reliability and the ability to identify college students at risk for psychosis. PMID- 25113070 TI - Thermally induced structural rearrangement of the Fe(II) coordination geometry in metallo-supramolecular polyelectrolytes. AB - Rigid rod-type metallo-supramolecular coordination polyelectrolytes with Fe(II) centres (Fe-MEPEs) are produced via the self-assembly of the ditopic ligand 1,4 bis(2,2':6',2''-terpyridine-4'-yl)benzene (tpy-ph-tpy) and Fe(II) acetate. Fe MEPEs exhibit remarkable electrochromic properties; they change colour from blue to transparent when an electric potential is applied. This electrochemical process is generally reversible. The blue colour in the ground state is a result of a metal-to-ligand charge transfer at the Fe(II) centre ion in a quasi octahedral geometry. When annealed at temperatures above 100 degrees C, the blue colour turns into green and the formerly reversible electrochromic properties are lost, even after cooling down to room temperature. The thermally induced changes in the Fe(II) coordination sphere are investigated in situ during annealing of a solid Fe-MEPE using X-ray absorption fine structure (XAFS) spectroscopy. The study reveals that the thermally induced transition is not accompanied by a redox process at the Fe(II) centre. From the detailed analysis of the XAFS spectra, the changes are attributed to structural changes in the coordination sphere of the Fe(II) site. In the low temperature state, the Fe(II) ion rests in a quasi octahedral coordination environment surrounded by six nitrogen atoms of the pyridine rings. The axial Fe-N bond length is 1.94 A, while the equatorial bond length amounts to 1.98 A. In the high temperature state, the FeN6-site exhibits a distortion with the axial Fe-N bonds being shortened to 1.88 A and the equatorial Fe-N bonds being elongated to 2.01 A. PMID- 25113069 TI - Mycobacteria entry and trafficking into endothelial cells. AB - Endothelial cells are susceptible to infection by mycobacteria, but the endocytic mechanisms that mycobacteria exploit to enter host cells and their mechanisms of intracellular transport are completely unknown. Using pharmacological inhibitors, we determined that the internalization of Mycobacterium tuberculosis (MTB), Mycobacterium smegmatis (MSM), and Mycobacterium abscessus (MAB) is dependent on the cytoskeleton and is differentially inhibited by cytochalasin D, nocodazole, cycloheximide, wortmannin, and amiloride. Using confocal microscopy, we investigated their endosomal trafficking by analyzing Rab5, Rab7, LAMP-1, and cathepsin D. Our results suggest that MSM exploits macropinocytosis to enter endothelial cells and that the vacuoles containing these bacteria fuse with lysosomes. Conversely, the entry of MTB seems to depend on more than one endocytic route, and the observation that only a subset of the intracellular bacilli was associated with phagolysosomes suggests that these bacteria are able to inhibit endosomal maturation to persist intracellularly. The route of entry for MAB depends mainly on microtubules, which suggests that MAB uses a different trafficking pathway. However, MAB is also able to inhibit endosomal maturation and can replicate intracellularly. Together, these findings provide the first evidence that mycobacteria modulate proteins of host endothelial cells to enter and persist within these cells. PMID- 25113071 TI - Laparoscopic intraoperative navigation surgery for gastric cancer using real-time rendered 3D CT images. AB - PURPOSE: Recent advances in laparoscopic surgical technology have made it possible to perform advanced high-level surgery, such as lymph node dissection for malignancy. Grasping the anatomy during such procedures is important for a safe operation. We have developed a new image information system that provides three-dimensional (3D) reconstructed CT images synchronized with the motion of the laparoscope. This study assesses this new navigation system. METHODS: Enhanced CT using a custom-made software program can provide 3D angiography images reconstructed as a laparoscopic view. A motion sensor mounted on the laparoscope can detect the direction angle of the laparoscope. The real-time rendered 3D CT images are synchronized with the laparoscopic video images according to the motion of the scope. These 3D CT images are projected on another monitor close to the laparoscopic video monitor. Lymph node dissection can be performed with the help of the real-time navigation system that provides a detailed 3D view of the vasculature. RESULTS: Ten laparoscopic gastrectomies were performed using this navigation system. Real-time intraoperative navigation of the vasculature was available, allowing for an excellent surgical outcome. No complications occurred in this series. CONCLUSION: Our intraoperative navigation system allows for safe laparoscopic gastric lymph node dissection. PMID- 25113073 TI - Novel behaviors of multiferroic properties in Na-Doped BiFeO3 nanoparticles. AB - Highly aliovalent Na(1+) ions were selected as the dopant to substitute Bi(3+) ions in BiFeO3 (BFO) and Bi1-xNaxFeO3 (x = 0, 0.01, 0.03, 0.05) nanoparticles prepared via a facile sol-gel method. Weak ferromagnetism and an obvious exchange bias (EB) phenomenon without field cooling were observed in the samples. To establish the presence of EB in the nanoparticles, training effect (TE) data were analyzed using Binek's model. Moreover, with the increase in Na(1+) content, the band gap was decreased, while interestingly, the leakage current density was significantly reduced and the smallest leakage current density (~10(-7) A cm(-2)) was observed for the 3% Na-doped BFO. The electrical conduction mechanism of samples was investigated by plotting log J versus log E. Oxygen vacancies decreased with the increase of Na content analyzed through X-ray photoelectron spectroscopy (XPS) measurements. To further explain the decrease of band gap and leakage current density with the increase of Na content, the interplay of oxygen vacancies and holes was analyzed and a phenomenological qualitative model based on the electronic energy band proposed. PMID- 25113074 TI - Synthesis of soluble, alkyne-substituted trideca- and hexadeca-starphenes. AB - Two literature-known TIPS-ethynyl-dibromoacenes were prepared and employed to synthesize cyclotrimers by using Yamamoto coupling conditions. Two large, well soluble starphenes were isolated in good yields. Crystallographic characterization verifies the triangular shape and shows significant differences in crystal packing. PMID- 25113072 TI - Hepatic resection for hepatocellular carcinoma in super-elderly patients aged 80 years and older in the first decade of the 21st century. AB - PURPOSE: We evaluated the preoperative and postoperative characteristics and prognosis of super-elderly patients with hepatocellular carcinoma (HCC). METHODS: Four hundred and thirty-one patients who underwent hepatic resection for HCC were classified into three groups according to their age at the time of surgery: super elderly (>=80 years; n = 20), elderly (70-80 years; n = 172) and younger (<70 years; n = 239). We compared the clinical characteristics, preoperative and postoperative factors and prognosis among the groups to evaluate whether liver resection is appropriate for super-elderly patients. RESULTS: The liver function was not significantly different among the groups. The proportion of patients with preoperative cardiovascular and respiratory disease and hypertension was higher in the super-elderly group compared to the other groups. The super-elderly group had shorter operations and reduced hemorrhage rates compared to the other groups. Postoperative cardiovascular complications and delirium were more frequently observed in the super-elderly group. The overall and tumor-free survival rates were not significantly different among the groups. Super-elderly patients had a lower rate of liver or HCC-related death and a higher rate of death due to other causes than the other groups. CONCLUSIONS: Super-elderly HCC patients who are appropriately evaluated and selected might have a favorable prognosis after undergoing hepatic resection. PMID- 25113075 TI - Two-dimensional structured illumination microscopy. AB - In widefield fluorescence microscopy, images from all but very flat samples suffer from fluorescence emission from layers above or below the focal plane of the objective lens. Structured illumination microscopy provides an elegant approach to eliminate this unwanted image contribution. To this end a line grid is projected onto the sample and phase images are taken at different positions of the line grid. Using suitable algorithms 'quasi-confocal images' can be derived from a given number of such phase-images. Here, we present an alternative structured illumination microscopy approach, which employs two-dimensional patterns instead of a one-dimensional one. While in one-dimensional structured illumination microscopy the patterns are shifted orthogonally to the pattern orientation, in our two-dimensional approach it is shifted at a single, pattern dependent angle, yet it already achieves an isotropic power spectral density with this unidirectional shift, which otherwise would require a combination of pattern shift and -rotation. Moreover, our two-dimensional approach also yields a better signal-to-noise ratio in the evaluated image. PMID- 25113076 TI - Preventing Malaria among Children in Zambia: The Role of Mother's Knowledge. AB - Malaria remains a devastating disease in Zambia, responsible for about 13% of deaths among children under age 5. Lack of malaria-specific knowledge has been commonly assumed to be an important barrier to engagement in behaviors that prevent malaria. To the best of our knowledge, this is the first study that accounts for the endogeneity of maternal knowledge in household's ownership of insecticide-treated nets (ITN), child's use of ITN, and household's protection against mosquitos (HSP). We account for the endogeneity of maternal knowledge through discrete factor and standard instrumental variable estimators. We find significant causal effects of maternal knowledge on the child's use of ITN and HSP but no significant effect on ownership of ITN. The causal effects of maternal knowledge on the use of ITN and HSP are strikingly larger in magnitude than the effects in the reduced form models. PMID- 25113077 TI - Is change in environmental supportiveness between primary and secondary school associated with a decline in children's physical activity levels? AB - Using a sample of English schoolchildren, we evaluate whether a change in school local area environmental supportiveness between primary and secondary school is associated with changes in active travel behaviours and physical activity levels. Participant's activity levels and travel behaviours were recorded for a week during their primary school final year and secondary school first year. Environmental supportiveness was evaluated using a Geographical Information System. Children attending both a primary and secondary school with a more supportive local environment were more likely to maintain active travel behaviours than those with less supportive environments. However, no trends were apparent with change in school supportiveness and change in physical activity. Policies that focus on the maintenance and uptake of active travel behaviours may help maintain children's physical activity levels into adolescence. PMID- 25113078 TI - Blood-brain barrier breakdown in reduced uterine perfusion pressure: a possible model of posterior reversible encephalopathy syndrome. AB - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinical entity characterized by headaches, altered mental status, seizures, and visual disturbances and is associated with white matter vasogenic edema. There are no experimental models to study PRES brain changes. METHODS: Twenty-eight pregnant Wistar rats were divided into 4 groups of 7: (1) pregnant-control; (2) reduced uterine perfusion pressure (RUPP); (3) invasive blood pressure (IBP); and (4) reduced uterine perfusion pressure plus invasive blood pressure (RUPP-IBP). The RUPP and RUPP-IBP groups were submitted to a reduction of uterine perfusion pressure at pregnancy days 13 to 15. The invasive mean arterial pressure of the IBP and RUPP-IBP groups was measured on day 20. The blood-brain barriers (BBBs) of all groups were analyzed using 2% Evans Blue dye on day 21. RESULTS: RUPP rats had higher blood pressures and increased BBB permeability to Evans Blue dye compared with the control animals. Brain staining occurred in 11 of 14 RUPP rats and in none of the control groups (P < .0001). CONCLUSIONS: The physiopathology of PRES remains unclear. Here, we described the use of RUPP rats as a potential model to better comprehend this syndrome. PMID- 25113079 TI - Investigating the utility of previously developed prediction scores in acute ischemic stroke patients in the stroke belt. AB - BACKGROUND: To assess the utility of previously developed scoring systems, we compared SEDAN, named after the components of the score (baseline blood Sugar, Early infarct signs and (hyper) Dense cerebral artery sign on admission computed tomography scan, Age, and National Institutes of Health Stroke Scale on admission), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra arterial Therapy (HIAT), and HIAT-2 scoring systems among patients receiving systemic (intravenous [IV] tissue plasminogen activator [tPA]) and endovascular (intra-arterial [IA]) treatments. METHODS: We retrospectively reviewed all IV tPA and IA patients presenting to our center from 2008-2011. The scores were assessed in patients who were treated with IV tPA only, IA only, and a combination of IV tPA and IA (IV-IA). We tested the ability of THRIVE to predict discharge modified Rankin scale (mRS) 3-6, HIAT and HIAT-2 discharge mRS 4-6, and SEDAN symptomatic intracerebral hemorrhage (sICH). RESULTS: Of the 366 patients who were included in this study, 243 had IV tPA only, 89 had IA only, and 34 had IV-IA. THRIVE was predictive of mRS 3-6 in the IV-IA (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.30-2.91) and the IV group (OR, 1.71; 95% CI, 1.43-2.04), but not in the IA group. HIAT was predictive of mRS 4-6 in the IA (OR, 3.55; 95% CI, 1.65 7.25), IV (OR, 3.47; 95% CI, 2.26-5.33), and IV-IA group (OR, 6.48; 95% CI, 1.41 29.71). HIAT-2 was predictive of mRS 4-6 in the IA (OR, 1.39; 95% CI, 1.03-1.87) and IV group (OR, 1.36; 95% CI, 1.18-1.57), but not in the IV-IA group. SEDAN was not predictive of sICH in the IA or the IV-IA group, but was predictive in the IV group (OR, 1.54; 95% CI, 1.01-2.36). CONCLUSIONS: Our study demonstrated that although highly predictive of outcome in the original study design treatment groups, prediction scores may not generalize to all patient samples, highlighting the importance of validating prediction scores in diverse samples. PMID- 25113081 TI - Stroke-induced immune depression-a randomized case control study in Kashmiri population of North India. AB - BACKGROUND: Stroke leads to transient immunedepression, which leads to increased incidence of poststroke infections. Because infection is one of the most common causes of increased mortality in patients with stroke, this study was undertaken to document immunedepression after stroke in our population. METHODS: A case controlled study wherein 39 patients with acute ischemic stroke in the age group of 18 and 60 years without any evidence of previous immunedepression were included. Interleukin 6 (IL-6) and interleukin 10 (IL-10) levels were checked in plasma in both the groups on day 3 and day 45. Also Cortisol and epinephrine levels were checked in the urine samples collected on day 3 and day 8. RESULTS: No significant difference was seen between the IL-6 and the IL-10 levels in samples collected on day 3 between the controls and cases, whereas Cortisol and norepinephrine were significantly raised in samples collected on day 3 in cases who developed infection as compared with controls. CONCLUSIONS: The higher levels of urinary cortisol and norepinephrine were observed in patients with stroke who developed infections, which indirectly reflected increased amount of stroke related stress. Furthermore, the levels of plasma IL-6 and IL-10 were also elevated in the same group of patients, which means transformation of immunecompetence to immunedepression, which is responsible for higher mortality. Subsequently on recovery from infection the plasma levels of interleukins and urinary cortisol and norepinephrine did not show any difference, which indirectly means recovery of the immune system on recovery from acute stage of stroke. Mortality in the patients with infection was increased than controls. PMID- 25113080 TI - Intravenously administered tissue plasminogen activator useful in milder strokes? A meta-analysis. AB - BACKGROUND: The dilemma of whether to treat mild strokes with tPA is a chronic problem. We performed a meta-analysis and metaregression of the published literature to determine the best definition of mild strokes and if intravenously administered tissue plasminogen activator (IV-tPA) is beneficial. METHODS: PubMed, Embase, Science Direct, and Cochrane CENTRAL were searched from inception to May 2013. The search terms used were "stroke," "cerebral infarct," "mild stroke," "minor stroke," "small infarct," "modified Rankin scale," "National Institutes of Health Stroke Scale (NIHSS) score," "stroke thrombolysis," and their combinations. Studies were included if they (1) involved 5 or more human patients with stroke; (2) analyzed modified Rankin scale (mRS) scores as the main variables of interest; (3) presented outcomes for NIHSS scores less than 6, 5, 4, or 3 points. Good outcomes were defined as mRS scores 0-1, and other outcomes studied were intracranial hemorrhage and mortality. RESULTS: Of 894 articles, 30 articles met our criteria. Only 8 articles provided patients arms with and without tPA treatment. A total of 637 patients with IV-tPA treatment and 568 without thrombolysis were included in analysis. Good outcomes were associated with tPA and just reached statistical significance (pooled odds ratio [OR], 1.319; 95% confidence interval [CI], 1.004-1.733; z = 1.987; P = .047). There were moderate levels of heterogeneity between studies (tau(2) = .346; Q = 19.974; df = 7; P = .006; I(2) = 64.954). On metaregression of a-priori sources of heterogeneity within individuals, we found age (B = -.37; z = -2.496; P = .012) to be a significant moderator. Mortality was not significantly different between IV-tPA-treated and nonthrombolyzed groups (pooled OR 1.095; 95% CI, .438-2.738; z = .193; P = .847). CONCLUSIONS: Patients with mild stroke may derive benefit from intravenous thrombolysis without a significant increase in mortality. PMID- 25113082 TI - Poor awareness of stroke--a hospital-based study from South India: an urgent need for awareness programs. AB - BACKGROUND: Stroke treatment has reached a new benchmark with thrombolytic therapy. However, India has witnessed a tremendous increase in morbidity and mortality of stroke over the past few decades. The prime deciding factor is initiation of treatment within the time window, which requires early recognition of stroke symptoms. We wished to analyze the lacunae in the stroke knowledge in our population. This hospital-based study assessed awareness of the public regarding stroke. METHODS: Two trained medical students interviewed accompanying relatives using a structured questionnaire. Data were analyzed using Statistical Package for the Social Sciences, version 20. Univariate and multivariate analyses were done. Descriptive results are presented as mean +/- SD. P less than .05 was considered as statistically significant. RESULTS: In total, 350 individuals formed the study group; mean age was 40.23 +/- 13.4 years constituting 145 males (47.5%) and 205 females (58.5%). Only 50 (14%) respondents could identify that the patient had developed stroke; however, 35% respondents identified brain as the organ involved for the presenting complaints and 34% could identify the warning symptoms of stroke, limb weakness being the most common (30%). Sources of information were friends and media (8%). Median time of reaching the hospital was 10 hours with patients transported by ambulance reaching early (P < .03); 80% of patients were fed in drowsy state during transport. More than 50% of the respondents were not able to identify the risk factors nor were aware that stroke is a preventable or a life-threatening disease. Multivariate logistic regression analysis confirmed that higher level of education was the only variable, which correlated with the organ identification (P < .001), stroke recognition (P < .002), and identification of the warning symptoms (P < .001). CONCLUSIONS: This hospital-based study reveals that there is a poor knowledge of recognition of stroke, its warning signs, risk factors, and prehospital care. There is an urgent need to design stroke awareness programs in the country with emphasis on ambulance service to minimize the time to thrombolysis. PMID- 25113083 TI - Predicting walking function of patients one month poststroke using modified Rivermead mobility index on admission. AB - Being able to predict walking ability of patients with stroke at an early stage is useful in formulating realistic rehabilitation goals and facilitating early discharge planning, which are beneficial not only to the patients but their family members and health care providers. This study aimed to use the modified Rivermead mobility index (MRMI) of the stroke patients on day 3 of their admission to predict their independent walking ability on day 28 postadmission. A total of 232 patients with acute stroke who were admitted to the acute hospital were recruited. Fifty-three percent of them (n = 123) were able to achieve independent walking ability after 28 days of admission whereas 47.0% of them (n = 109) failed to do so. The receiver operating characteristics curve analysis was performed. The optimal cutoff score with the highest sum of sensitivity and specificity was found to be 18.5 (sensitivity, 85.0%; specificity, 75.0%) and the area under the curve was .880. In conclusion, MRMI on day 3 of admission maybe useful in predicting independent walking ability 1 month after stroke. PMID- 25113085 TI - The impact of prior antithrombotic status on cerebral infarction in patients with atrial fibrillation. AB - BACKGROUND: Anticoagulation effectively prevents cardioembolic stroke in atrial fibrillation (AF) patients, whereas it is less effective than antiplatelet therapy (AT) in noncardioembolic stroke prevention. We hypothesized that the ischemic lesion pattern and vascular patency would differ according to the antithrombotic treatment status in AF patients. METHODS: The medical records of 1078 acute ischemic stroke patients with AF were retrospectively reviewed. Patients were classified according to medication at stroke onset: (1) optimal anticoagulation (OAC; international normalized ratio [INR] 1.7-3.0; n = 36); (2) suboptimal anticoagulation (SOAC; INR <=1.7; n = 134); (3) AT (n = 285); and (4) control (no antithrombotic medication; n = 623). Imaging and clinical variables of each group were compared with that of controls. RESULTS: Small cortical or single subcortical infarctions were more common in the OAC group than in controls (6% vs. 1% and 22% vs. 8%, respectively; standardized residual, 2.4 and 2.8). Multicirculatory infarctions were less common in the OAC group than in controls (0% vs. 11%; standardized residual, -2.0). Obstruction of the corresponding artery was less common in the OAC group than in controls (26.5% vs. 46.5%, P = .02). Initial neurologic severity was lower in the OAC and AT groups than in controls (P = .01 and .03, respectively). OAC and AT were independently associated with favorable functional outcome at 3-months (P = .015 and <.001, respectively). CONCLUSIONS: Ischemic stroke can occur during OAC in AF patients. Small cortical or single subcortical lesions were more common than typical cardioembolic lesion patterns. OAC and AT were protective against severe neurologic deficit and independently associated with favorable outcome, but SOAC was not. PMID- 25113084 TI - Intravenous fibrinolysis eligibility: a survey of stroke clinicians' practice patterns and review of the literature. AB - BACKGROUND: The indications and contraindications for intravenous (IV) recombinant tissue plasminogen activator (rtPA) use in ischemic stroke can be confusing to the practicing neurologist. Here we seek to describe practice patterns regarding decision-making among US stroke clinicians. METHODS: Stroke clinicians (attending and fellow) from the 8 National Institutes of Health SPOTRIAS (Specialized Programs of Translational Research in Acute Stroke) centers were asked to complete a survey ahead of the 2012 SPOTRIAS Investigators' meeting. RESULTS: A total of 51 surveys were collected (71% response rate). Most of the responders were attending physicians (68%). Only 18% of clinicians reported strictly adhering to current American Heart Association guidelines for treatment within 3 hours from symptom onset; this increased to 51% for the European Cooperative Acute Stroke Study (ECASS) III criteria in the 3 to 4.5 hours time frame. All clinicians treat eligible patients in the 3 to 4.5 hours time frame. The great majority will recommend rtPA in the following scenarios: (1) elderly individuals irrespective of age (97%); (2) severe stroke irrespective of National Institutes of Health Stroke Scale (NIHSS) (95%); or (3) suspected stroke with seizures at symptom onset (91%). None recommended rtPA in the setting of an international normalized ratio >1.7. Most clinicians defined mild strokes as an exclusion based on the perceived disability of the deficit (80%) rather than on a specific NIHSS threshold. CONCLUSIONS: Most surveyed stroke clinicians seem to find that the current IV rtPA eligibility criteria for the 3-hour time frame too restrictive. All would recommend rtPA to eligible patients in the 3 to 4.5 hours time frame despite the absence of an U.S. Food and Drug Administration (FDA)-approved indication. PMID- 25113087 TI - Revision of Beardius Reiss et Sublette, 1985 (Diptera: Chironomidae), with the description of twenty new species. AB - The genus Beardius Reiss et Sublette, 1985 is revised and twenty new species, Beardius abbadi sp. n., B. arawak sp. n., B. bizzoi sp. n., B. bucephalus sp. n., B. curticaudatus sp. n., B. dioi sp. n., B. hirtidorsum sp. n., B. krenak sp. n., B. kumadueni sp. n., B. longicaudatus sp. n., B. mileneae sp. n., B. nebularius sp. n., B. neusae sp. n., B. novoairensis sp. n., B. phoenix sp. n., B. sapiranga sp. n., B. tupinamba sp. n., B. vanessae sp. n., and B. yperoig sp. n. from Brazil and Beardius chapala sp. n. from Mexico are described and figured. Further, the female, pupa and larva of B. urupeatan Pinho, Mendes et Andersen and the female and larva of B. cristhinae Trivinho-Strixino et Siqueira are described, and new records of Brazilian species are provided. Emended diagnoses for all stages and sexes are given. The phylogeny of the genus is outlined and seven tentative species groups, the parcus group, the truncatus group, the tupinamba group, the triangulatus group, the bucephalus group, the xylophilus group, and the roquei group, are proposed. Keys to males, females, pupae and larvae are provided. PMID- 25113086 TI - Over-the-counter and prescription sleep medication and incident stroke: the REasons for Geographic and Racial Differences in Stroke study. AB - BACKGROUND: Preliminary evidence suggests sleep medications are associated with risk of vascular events; however, the long-term vascular consequences are understudied. This study investigated the relation between sleep medication use and incident stroke. METHODS: Within the REasons for Geographic And Racial Differences in Stroke study, 21,678 black participants and white participants (>=45 years) with no history of stroke were studied. Participants were recruited from 2003 to 2007. From 2008 to 2010, participants self reported their prescription and over-the-counter sleep medication use over the past month. Suspected stroke events were identified by telephone contact at 6-month intervals and associated medical records were retrieved and physician-adjudicated. Proportional hazards analysis was used to estimate hazard ratios for incident stroke associated with sleep medication use (0, 1-14, and 15+ days per month) controlling for sociodemographics, stroke risk factors, mental health symptoms, and sleep apnea risk. RESULTS: At the sleep assessment, 9.6% of the sample used prescription sleep medication and 11.1% used over-the-counter sleep aids. Over an average follow-up of 3.3 +/- 1.0 years, 297 stroke events occurred. Over-the counter sleep medication use was associated with increased risk of incident stroke in a frequency-response relationship (P = .014), with a 46% increased risk for 1-14 days of use per month (hazards ratio [HR] = 1.46; 95% confidence interval [CI], .99-2.15) and a 65% increased risk for 15+ days (HR = 1.65; 95% CI, .96-2.85). There was no significant association with prescription sleep medications (P = .80). CONCLUSIONS: Over-the-counter sleep medication use may independently increase the risk of stroke beyond other risk factors in middle aged to older individuals with no history of stroke. PMID- 25113088 TI - Watching individual molecules flex within lipid membranes using SERS. AB - Interrogating individual molecules within bio-membranes is key to deepening our understanding of biological processes essential for life. Using Raman spectroscopy to map molecular vibrations is ideal to non-destructively 'fingerprint' biomolecules for dynamic information on their molecular structure, composition and conformation. Such tag-free tracking of molecules within lipid bio-membranes can directly connect structure and function. In this paper, stable co-assembly with gold nano-components in a 'nanoparticle-on-mirror' geometry strongly enhances the local optical field and reduces the volume probed to a few nm(3), enabling repeated measurements for many tens of minutes on the same molecules. The intense gap plasmons are assembled around model bio-membranes providing molecular identification of the diffusing lipids. Our experiments clearly evidence measurement of individual lipids flexing through telltale rapid correlated vibrational shifts and intensity fluctuations in the Raman spectrum. These track molecules that undergo bending and conformational changes within the probe volume, through their interactions with the environment. This technique allows for in situ high-speed single-molecule investigations of the molecules embedded within lipid bio-membranes. It thus offers a new way to investigate the hidden dynamics of cell membranes important to a myriad of life processes. PMID- 25113090 TI - [Surgical characteristics of small parathyroid gland adenomas]. PMID- 25113089 TI - [Shoulder dislocation in athletes]. AB - BACKGROUND: Shoulder dislocation is a common injury in athletes. Surgical and non surgical therapy options are still the subject of controversial debate. STUDY AIM: This article presents important considerations for decision-making and current concepts for the therapy of shoulder dislocation in athletes. METHODS: A selective literature search was carried out in PubMed. RESULTS: Surgical and non surgical therapy options are described in the literature without yet defining a gold standard. CONCLUSION: Early surgical stabilization is currently recommended in young athletes. For decision-making numerous sport and patient-related factors need to be considered. Most athletes are able to return to the pre-injury level after surgical stabilization. PMID- 25113091 TI - [Perioperative treatment with pasireotide reduces the rate of postoperative pancreatic fistula]. PMID- 25113093 TI - Detection of the motor points of the abdominal muscles. AB - PURPOSE: Abdominal functional electrical stimulation (AFES) is a technique intended to improve respiratory function in tetraplegia where breathing is affected due to abdominal muscle paralysis. Although it is known that optimal muscle contraction is achieved when electrical stimulation is applied close to the muscle motor point, AFES studies have used a variety of electrode positions. This study aims to investigate the feasibility of using Neuromuscular Electrical Stimulation to detect the motor points of the abdominal muscles, and to evaluate the intrasubject repeatability and intersubject uniformity of their positions, to find the most suitable AFES electrode location. METHODS: Low frequency stimulation (0.5 Hz) was applied to the abdominal muscles of 10 able bodied and five tetraplegic participants. The electrode positions which achieved the strongest muscle contractions were recorded as the motor point positions, with measurements repeated once. For five able bodied participants, assessments were repeated after 18 months, in seated and supine positions. RESULTS: Intersubject uniformity ranged from 2.8 to 8.8%. Motor point positions were identified with intrasubject repeatability of <1.7 cm, deemed adequate relative to standard AFES electrode size. Intrasubject repeatability shows motor point positions changed little (<1.7 cm) after 18 months but varied between seated and supine positions with repeatability of up to 3.1 cm. CONCLUSIONS: A simple technique to locate the motor points of the abdominal muscles is presented and shown to have an adequate intrasubject repeatability, enabling the optimum AFES electrode location to be identified for each user. PMID- 25113094 TI - Reliability of H-reflex in vastus lateralis and vastus medialis muscles during passive and active isometric conditions. AB - PURPOSE: This study aimed to evaluate the modulation and reliability of the vastus medialis (VM) and vastus lateralis (VL) H-reflexes in both passive and active conditions. METHODS: Recruitment curves of VM and VL H-reflexes and M waves at rest and during muscle contraction (30% of maximal voluntary contraction) were performed for 12 healthy males and were then repeated after 1 h, 1 day and 1 week. The maximal H-reflexes of each muscle were normalized to their respective maximal M-waves (H/M ratio) and absolute (CV) and relative (ICC) reliability were calculated. RESULTS: The H-reflex was potentiated in active compared to passive condition and a higher H-reflex occurrence (12 vs. 10 subjects) and amplitude (~+150%) was found for the VM compared to the VL in active condition. The intra- (ICChour = 0.97) and inter-day (ICCday = 0.92; ICCweek = 0.92) reliability was poor for the passive VM H/M ratio due to high within-subject variations (CVhour = 52.2%; CVday = 69.8%; CVweek = 60.9%) whereas for the active condition the reliability, especially intra-day, was good (ICChour = 0.93 and CVhour = 12%; ICCday = 0.86 and CVday = 14.5%; ICCweek = 0.79 and CVweek = 19.7%). CONCLUSIONS: This study showed differential modulation of the H reflex between vasti muscles of the quadriceps and a higher occurrence and reliability for the active VM H-reflex. One can therefore conclude that it seems more appropriate to evoke quadriceps VM H-reflex (rather than VL) during an isometric muscle contraction. PMID- 25113095 TI - High-dose inhaled terbutaline increases muscle strength and enhances maximal sprint performance in trained men. AB - PURPOSE: The purpose of the present study was to investigate the effect of high dose inhaled terbutaline on muscle strength, maximal sprinting, and time-trial performance in trained men. METHODS: Nine non-asthmatic males with a VSO2max of 58.9 +/- 3.1 ml min(-1) kg(-1) (mean +/- SEM) participated in a double-blinded randomized crossover study. After administration of inhaled terbutaline (30 * 0.5 mg) or placebo, subjects' maximal voluntary isometric contraction (MVC) of m.quadriceps was measured. After MVC, subjects performed a 30-s Wingate test. Sixty minutes following the Wingate test, subjects exercised for 10 min at 80% of VSO2max and completed a 100-kcal time trial. Aerobic contribution was determined during the Wingate test by indirect calorimetry. Furthermore, plasma terbutaline, lactate, glucose, and K(+) were measured. RESULTS: Inhalation of 15 mg terbutaline resulted in systemic concentrations of terbutaline of 23.6 +/- 1.1 ng ml(-1) 30 min after administration, and elevated plasma lactate (P = 0.001) and glucose (P = 0.007). MVC was higher for terbutaline than placebo (738 +/- 64 vs. 681 +/- 68 N) (P = 0.007). In addition, Wingate peak power and mean power were 2.2 +/- 0.8 (P = 0.019) and 3.3 +/- 1.0% (P = 0.009) higher for terbutaline than placebo. Net accumulation of plasma lactate was higher (P = 0.003) for terbutaline than placebo during the Wingate test, whereas [Formula: see text] above baseline was unchanged by terbutaline (P = 0.882). Time-trial performance was not different between treatments (P = 0.236). CONCLUSION: High-dose inhaled terbutaline elicits a systemic response that enhances muscle strength and sprint performance. High-dose terbutaline should therefore continue to be restricted in competitive sport. PMID- 25113097 TI - Muscle activation during low- versus high-load resistance training in well trained men. AB - PURPOSE: It has been hypothesized that lifting light loads to muscular failure will activate the full spectrum of MUs and thus bring about muscular adaptations similar to high-load training. The purpose of this study was to investigate EMG activity during low- versus high-load training during performance of a multi joint exercise by well-trained subjects. METHODS: Employing a within-subject design, 10 young, resistance-trained men performed sets of the leg press at different intensities of load: a high-load (HL) set at 75% of 1-RM and a low-load (LL) set at 30% of 1-RM. The order of performance of the exercises was counterbalanced between participants, so that half of the subjects performed LL first and the other half performed HL first, separated by 15 min rest. Surface electromyography (EMG) was used to assess mean and peak muscle activation of the vastus medialis, vastus lateralis, rectus femoris, and biceps femoris. RESULTS: Significant main effects for trials and muscles were found (p < 0.01). Significantly greater peak EMG activity was found during the HL set (M = 177.3, SD = 89.53) compared to the LL set (M = 137.73, SD = 95.35). Significantly greater mean EMG activity was found during the HL set (M = 63.7, SD = 37.23) compared to the LL set (M = 41.63, SD = 28.03). CONCLUSIONS: Results indicate that training with a load of 30% 1-RM to momentary muscular failure does not maximally activate the full motor unit pool of the quadriceps femoris and hamstrings during performance of multi-joint lower body exercise. PMID- 25113098 TI - Origin, patterns and anthropogenic accumulation of potentially toxic elements (PTEs) in surface sediments of the Aviles estuary (Asturias, northern Spain). AB - Sediment quality has been assessed within the Aviles estuary, an important industrial area in the NW of Spain. The study started with a geochemical characterization of the superficial sediments that revealed some anomalous metal(oid)s concentrations in sensitive areas such as beaches or dunes. These data were studied by means of multivariate statistical techniques and enrichment factors calculation to evaluate the correlations and geochemical origin within the different elements. A novel approach using the combination of enrichment factors with a sequential application of factor analysis, clustering and kriging was essential to identify the possible sources of pollution. The collected information suggested that Cd (strongly correlated with Zn and Pb) was the potentially toxic element most widely distributed and problematic. Furthermore, particulate emissions from Zn metallurgy, as well as dust generated by the mineral loading and stockpile activities in the port were identified as the most important sources of pollution. PMID- 25113099 TI - Resilience of branching and massive corals to wave loading under sea level rise- a coupled computational fluid dynamics-structural analysis. AB - Measurements of coral structural strength are coupled with a fluid dynamics structural analysis to investigate the resilience of coral to wave loading under sea level rise and a typical Great Barrier Reef lagoon wave climate. The measured structural properties were used to determine the wave conditions and flow velocities that lead to structural failure. Hydrodynamic modelling was subsequently used to investigate the type of the bathymetry where coral is most vulnerable to breakage under cyclonic wave conditions, and how sea level rise (SLR) changes this vulnerability. Massive corals are determined not to be vulnerable to wave induced structural damage, whereas branching corals are susceptible at wave induced orbital velocities exceeding 0.5m/s. Model results from a large suite of idealised bathymetry suggest that SLR of 1m or a loss of skeleton strength of order 25% significantly increases the area of reef flat where branching corals are exposed to damaging wave induced flows. PMID- 25113101 TI - Evaluation of potential relationships between benthic community structure and toxic metals in Laizhou Bay. AB - The objective of the present study was to examine the relationships between benthic community structure and toxic metals using bivariate/multivariate techniques at 17 sediment locations in Laizhou Bay, North China. Sediment chemical data were evaluated against geochemical background values and sediment quality guidelines, which identified Cu and As as contaminants of concern with a moderate potential for adverse effects. Benthic community data were subjected to non-metric multidimensional scaling, which generated four groups of stations. Spearman rank correlation was then employed to explore the relationships between the major axes of heavy metals and benthic community structure. However, weak and insignificant correlations were found between these axes, indicating that contaminants of concern may not be the primary explanatory factors. Polychaeta were abundant in southern Laizhou Bay, serving as a warning regarding the health status of the ecosystem. Integrated sediment quality assessment showed sediments from northern central locations were impaired, displaying less diverse benthos and higher metal contamination. PMID- 25113102 TI - Trace metal variability, background levels and pollution status assessment in line with the water framework and Marine Strategy Framework EU Directives in the waters of a heavily impacted Mediterranean Gulf. AB - The aim of this work is to assess trace metal pollution status (Cd, Cu, Ni, Pb, Zn) in the waters of Saronikos Gulf, Greece, in line with the WFD and MSFD European Directives, based on data collected over a decade (2000-2010). Dissolved metal background levels are estimated for the first time for Greek marine waters and the upper limits are: Cd: 0.574 nmol L(-1); Cu: 8.26 nmol L(-1); Ni: 7.94 nmol L(-1); Pb: 2.60 nmol L(-1); Zn: 115 nmol L(-1). The variability of dissolved and particulate metals reflected the presence of several point sources and revealed the importance of natural mechanisms acting as non-point sources. The status of Saronikos Gulf is classified as 'High' for most metals studied. An exception to this is the enclosed Elefsis Bay where Cu, Ni and Zn concentrations are found above background. Our work will assist the implementation of WFD and MSFD directives in Greece. PMID- 25113100 TI - Decalcification of benthic foraminifera due to "Hebei Spirit" oil spill, Korea. AB - In order to determine the effects on foraminifera due to spilled crude oil in the "Herbei Spirit" incident, a study of benthic foraminiferal assemblages was carried out on sediment samples collected from the Sogeunri tidal flat, Taean Peninsula, Korea. Breakages of the chambers in the Ammonia beccarii and Elphidium subincertum species of the Sogeunri tidal flat with a low pH (6.98 on average) were marked. These chamber breakages occurred in 71.6% of A. beccarii and are thought to be caused by decalcification due to the fall in pH resulting from the "Hebei Spirit" oil spill. The factors that affect breakage of the chamber in benthic foraminifera under low pH condition may be not only deto decalcification but also to exposure duration of substrata in the tidal flat spilled crude oil. PMID- 25113103 TI - A three-step model to assess shoreline and offshore susceptibility to oil spills: the South Aegean (Crete) as an analogue for confined marine basins. AB - This study combines bathymetric, geomorphological, geological data and oil spill predictions to model the impact of oil spills in two accident scenarios from offshore Crete, Eastern Mediterranean. The aim is to present a new three-step method of use by emergency teams and local authorities in the assessment of shoreline and offshore susceptibility to oil spills. The three-step method comprises: (1) real-time analyses of bathymetric, geomorphological, geological and oceanographic data; (2) oil dispersion simulations under known wind and sea current conditions; and (3) the compilation of final hazard maps based on information from (1) and (2) and on shoreline susceptibility data. The results in this paper show that zones of high to very-high susceptibility around the island of Crete are related to: (a) offshore bathymetric features, including the presence of offshore scarps and seamounts; (b) shoreline geology, and (c) the presence near the shore of sedimentary basins filled with unconsolidated deposits of high permeability. Oil spills, under particular weather and oceanographic conditions, may quickly spread and reach the shoreline 5-96 h after the initial accident. As a corollary of this work, we present the South Aegean region around Crete as a valid case-study for confined marine basins, narrow seaways, or interior seas around island groups. PMID- 25113104 TI - Uncertainty analysis of total phosphorus spatial-temporal variations in the Yangtze River Estuary using different interpolation methods. AB - Interpolation processes and results are generally accompanied by uncertainty which affects the spatial and temporal properties of pollutants. Based on the 4 period sample data of total phosphorus (TP) collected from the Yangtze River Estuary (YRE) in 2010 and 2011, the uncertainty of spatial-temporal variation was analyzed with interpolation methods of inverse distance weighted (IDW), local polynomial interpolation (LPI), ordinary kriging (OK) and disjunctive kriging (DK). The root mean square errors (RMSE) and the mean relative errors (MRE) were used to analyze the accuracy of different interpolation methods. The results showed that the uncertainty of DK was the lowest and the uncertainty of LPI was the highest among the 4 methods. The subtraction results between different interpolation methods showed that there was some distinct area of value in the disparate interval (not in [-0.05, 0.05] (mg/L)) in the 4 seasonal results, which was mainly distributed in the boundary region and around some sample sites. Both standard deviation (SD) and coefficient of variance (CV) in August 2010 were the highest in the 4 seasons and annual mean. The uncertainty may be caused by choice of interpolation methods, spatial data discrepancy and the lack of sample data. PMID- 25113105 TI - [Is invasive therapy (medically/ethically) justifiable nearing an end of life situation, if it is based on symptom control and quality of life?]. AB - On the basis of a case study, the complex problems of an invasive therapy (gastroscopy with stentig) in an end of life situation will be demonstrated and discussed. The main problems of the 67-year-old patient with a gastric cardia carcinoma were the symptoms of nausea and vomiting, which were managed well with conservative treatment. The wish from the patient to eat was a highly ethical demand on the team of the palliative care unit. This paper shows the area of tension between the highly developed interventional endoscopic capabilities on the one hand and the reasonable treatment in end of life situations on the other. PMID- 25113106 TI - Master apical file size - smaller or larger: a systematic review of healing outcomes. AB - The purpose of this systematic review was to determine in patients undergoing root canal treatment, whether apical enlargement affected the healing outcome. A PICO (population, intervention, comparison and outcome) strategy was developed to identify studies dealing with apical size of canal and healing outcome as measured clinically and radiographically. The MEDLINE, Embase, Cochrane and PubMed databases were searched. Additionally, the bibliography of all relevant articles and textbooks was manually searched. Based on inclusion and exclusion criteria, two reviewers independently selected the relevant articles. Four articles were identified that met the inclusion criteria. There were no studies that evaluated apical enlargement and healing outcome using cone beam computed tomography. The results of the systematic review confirmed that more evidence based research in this area is needed. With the limited information available, the best current available clinical evidence suggests that for patients with necrotic pulps and periapical lesions, enlargement of the apical size would result in an increased healing outcome in terms of clinical and radiographic evaluations. PMID- 25113108 TI - Group conformity: the legacy continues. PMID- 25113109 TI - Medical schools: what counts as one, and why count them? PMID- 25113110 TI - Revealing the hidden curriculum and reducing cultural reproduction: small steps on a long road. PMID- 25113111 TI - When I say ... preparedness. PMID- 25113112 TI - The good and bad of group conformity: a call for a new programme of research in medical education. AB - CONTEXT: Given that a significant portion of medical education occurs in various social settings (small groups, large classes, clinical environments), it is critical to examine how group members interact. One type of influence on these interactions is conformity, whereby an individual changes his or her own behaviour to match incorrect responses of others in a group. Conformity to peer pressure has been replicated in experimental research conducted in many countries over the last 60 years. There is newly emerging empirical evidence of this effect in medical education, suggesting that subtle motivations and pressures within a group may prevent students from challenging or questioning information that seems incorrect. OBJECTIVES: This narrative review aims to present an overview of theory and findings in research into conformity in the fields of social psychology, business, sociology and aviation theory to demonstrate its direct relevance to medical education and the health professions. METHODS: We searched online databases (MEDLINE, PubMed, PsycINFO and ProQuest) from the University of Calgary catalogue. We also searched citations in articles reviewed and references provided by colleagues. We limited our narrative review to publications released between 1950 and 2012. RESULTS: Group conformity behaviour may be one of a number of communication challenges associated with interprofessional care, and may represent a factor contributing to the burden of adverse events. This paper calls for a new programme of research into conformity in medical education that provides systematic empirical evidence of its relevance and applications in education, health care and practice. CONCLUSIONS: This review reveals decades of anecdotal and empirical evidence that conformity is a pervasive phenomenon across disciplines. Further research is needed to elucidate which situations pose the greatest risk for the occurrence of conformity, how to manage it in practice and its implications for patient safety. PMID- 25113113 TI - Overview of the world's medical schools: an update. AB - CONTEXT: That few data are available on the characteristics of medical schools or on trends within medical education internationally constitutes a major challenge when developing strategies to address physician workforce shortages. Quality and up-to-date information is needed to improve health and education policy planning. METHODS: We used publicly available data from the International Medical Education Directory and Avicenna Directories, and an internal education programme database to gather data on medical education provision worldwide. We sent a semi structured questionnaire to a selection of 346 medical schools, of which 218 (63%) in 81 different countries or territories replied. We contacted ministries of health, national agencies for accreditation or similar bodies to clarify inconsistencies among sources. We identified key informants to obtain country level specific information. Descriptive statistics were used to analyse current medical school data by country. RESULTS: There are about 2600 medical schools worldwide. The countries with the largest numbers of schools are India (n = 304), Brazil (n = 182), the USA (n = 173), China (n = 147) and Pakistan (n = 86). One third of all medical schools are located in five countries and nearly half are located in 10 countries. Of 207 independent states, 24 have no medical school and 50 have only one. Regionally, numbers of citizens per school differ: the Caribbean region has one school per 0.6 million population; the Americas and Oceania each have one school per 1.2 million population; Europe has one school per 1.8 million population; Asia has one school per 3.5 million population, and Africa has one school per 5.0 million population. In 2012, on average, there were 181 graduates per medical school. CONCLUSIONS: The total number and distribution of medical schools around the world are not well matched with existing physician numbers and distribution. The collection and aggregation of medical school data are complex and would benefit from better information on local recognition processes. Longitudinal comparisons are difficult and subject to several sources of error. The consistency and quality of medical school data need to be improved to accurately document potential supply; one example of such an advancement is the World Directory of Medical Schools. PMID- 25113114 TI - Key-feature questions for assessment of clinical reasoning: a literature review. AB - OBJECTIVES: Key-feature questions (KFQs) have been developed to assess clinical reasoning skills. The purpose of this paper is to review the published evidence on the reliability and validity of KFQs to assess clinical reasoning. METHODS: A literature review was conducted by searching MEDLINE (1946-2012) and EMBASE (1980 2012) via OVID and ERIC. The following search terms were used: key feature; question or test or tests or testing or tested or exam; assess or evaluation, and case-based or case-specific. Articles not in English were eliminated. RESULTS: The literature search resulted in 560 articles. Duplicates were eliminated, as were articles that were not relevant; nine articles that contained reliability or validity data remained. A review of the references and of citations of these articles resulted in an additional 12 articles to give a total of 21 for this review. Format, language and scoring of KFQ examinations have been studied and modified to maximise reliability. Internal consistency reliability has been reported as being between 0.49 and 0.95. Face and content validity have been shown to be moderate to high. Construct validity has been shown to be good using vector thinking processes and novice versus expert paradigms, and to discriminate between teaching methods. The very modest correlations between KFQ examinations and more general knowledge-based examinations point to differing roles for each. Importantly, the results of KFQ examinations have been shown to successfully predict future physician performance, including patient outcomes. CONCLUSIONS: Although it is inaccurate to conclude that any testing format is universally reliable or valid, published research supports the use of examinations using KFQs to assess clinical reasoning. The review identifies areas of further study, including all categories of evidence. Investigation into how examinations using KFQs integrate with other methods in a system of assessment is needed. PMID- 25113115 TI - You've got to know the rules to play the game: how medical students negotiate the hidden curriculum of surgical careers. AB - OBJECTIVES: The hidden curriculum may be framed as the culture, beliefs and behaviours of a community that are passed to students outside formal course offerings. Medical careers involve diverse specialties, each with a different culture, yet how medical students negotiate these cultures has not been fully explored. Using surgery as a case study, we aimed to establish, first, whether a specialty-specific hidden curriculum existed for students, and second, how students encountered and negotiated surgical career options. METHODS: Using a constructivist grounded theory approach, we explored students' thoughts, beliefs and experiences regarding career decisions and surgery. An exploratory questionnaire informed the discussion schedule for semi-structured individual interviews. Medical students were purposively sampled by year group, gender and career intentions in surgery. Data collection and analysis were iterative: analysis followed each interview and guided the adaptation of our discussion schedule to further our evolving model. RESULTS: Students held a clear sense of a hidden curriculum in surgery. To successfully negotiate a surgical career, students perceived that they must first build networks because careers information flows through relationships. They subsequently enacted what they learned by accruing the accolades ('ticking the boxes') and appropriating the dispositions ('walking the talk') of 'future surgeons'. This allowed them to identify themselves and to be identified by others as 'future surgeons' and to gain access to participation in the surgical world. Participation then enabled further network building and access to careers information in a positive feedback loop. For some, negotiating the hidden curriculum was more difficult, which, for them, rendered a surgical career unattractive or unattainable. CONCLUSIONS: Students perceive a clear surgery-specific hidden curriculum. Using a constructivist grounded theory approach, we have developed a model of how students encounter, uncover and enact this hidden curriculum to succeed. Drawing on concepts of Bourdieu, we discuss unequal access to the hidden curriculum, which was found to exclude many from the possibility of a surgical career. PMID- 25113116 TI - 'We' not 'I': health advocacy is a team sport. AB - CONTEXT: Health advocacy, although recognised as a professional responsibility, is often seen as overwhelming, perhaps because it is framed conceptually as an activity that each physician should undertake alone rather than as a collaborative process. In the context of a study exploring how effective physician health advocates conceptualise their roles and their activities related to health advocacy, we uncovered data that speak directly of the issue of whether the activities of health advocates are enacted as individual or collective pursuits. METHODS: We interviewed ten physicians, identified by others as effective health advocates, regarding their advocacy activities. We collected and analysed data in an iterative process, informed by constructivist grounded theory, continuously refining the interview framework and examining evolving themes. The final coding scheme was applied to all transcripts. RESULTS: Health advocacy was viewed by these physicians as a collective activity. This collective construction of advocacy presented in three ways: (i) as teamwork by interprofessional teams of individuals with clearly defined roles and functional, task-oriented goals; (ii) as a process involving networks of resources or people that can be accessed for both support and reinforcement, and (iii) as a process involving collaborative think-tanks in which members contribute different perspectives to enact collective problem solving at a conceptual level. CONCLUSIONS: Effective health advocates do not conceptualise themselves as stand alone experts who must do everything themselves. Their collective approach makes it possible for these physicians to incorporate health advocacy into their clinical practice. However, although conceptualising health advocacy as a collective activity may make it less daunting, this way of understanding health advocacy is not compatible with current formal descriptions of the associated competencies. PMID- 25113117 TI - Feedback in action within bedside teaching encounters: a video ethnographic study. AB - CONTEXT: Feedback associated with teaching activities is often synonymous with reflection on action, which comprises the evaluative assessment of performance out of its original context. Feedback in action (as correction during clinical encounters) is an underexplored, complementary resource facilitating students' understanding and learning. OBJECTIVES: The purpose of this study was to explore the interactional patterns and correction modalities utilised in feedback sequences between doctors and students within general practice-based bedside teaching encounters (BTEs). METHODS: A qualitative video ethnographic approach was used. Participants were recorded in their natural settings to allow interactional practices to be contextually explored. We examined 12 BTEs recorded across four general practices and involving 12 patients, four general practitioners and four medical students (209 minutes and 20 seconds of data) taken from a larger corpus. Data analysis was facilitated by Transana video analysis software and informed by previous conversation analysis research in ordinary conversation, classrooms and health care settings. RESULTS: A range of correction strategies across a spectrum of underlying explicitness were identified. Correction strategies classified at extreme poles of this scale (high or low explicitness) were believed to be less interactionally effective. For example, those using abrupt closing of topics (high explicitness) or interactional ambiguity (low explicitness) were thought to be less effective than embedded correction strategies that enabled the student to reach the correct answer with support. CONCLUSIONS: We believe that educators who are explicitly taught linguistic strategies for how to manage feedback in BTEs might manage learning more effectively. For example, clinicians might maximise learning moments during BTEs by avoiding abrupt or ambiguous feedback practices. Embedded correction strategies can enhance student participation by guiding students towards the correct answer. Clinician corrections can sensitively manage student face-saving by minimising the exposure of student error to patients. Furthermore, we believe that the effective practices highlighted by our analysis might facilitate successful transformation of feedback in action into feedback for action. PMID- 25113118 TI - Supervising incoming first-year residents: faculty expectations versus residents' experiences. AB - CONTEXT: First-year residents begin clinical practice in settings in which attending staff and senior residents are available to supervise their work. There is an expectation that, while being supervised and as they become more experienced, residents will gradually take on more responsibilities and function independently. OBJECTIVES: This study was conducted to define 'entrustable professional activities' (EPAs) and determine the extent of agreement between the level of supervision expected by clinical supervisors (CSs) and the level of supervision reported by first-year residents. METHODS: Using a nominal group technique, subject matter experts (SMEs) from multiple specialties defined EPAs for incoming residents; these represented a set of activities to be performed independently by residents by the end of the first year of residency, regardless of specialty. We then surveyed CSs and first-year residents from one institution in order to compare the levels of supervision expected and received during the day and night for each EPA. RESULTS: The SMEs defined 10 EPAs (e.g. completing admission orders, obtaining informed consent) that were ratified by a national panel. A total of 113 CSs and 48 residents completed the survey. Clinical supervisors had the same expectations regardless of time of day. For three EPAs (managing i.v. fluids, obtaining informed consent, obtaining advanced directives) the level of supervision reported by first-year residents was lower than that expected by CSs (p < 0.001) regardless of time of day (i.e. day or night). For four more EPAs (initiating the management of a critically ill patient, handing over the care of a patient to colleagues, writing a discharge prescription, coordinating a patient discharge) differences applied only to night-time work (p <= 0.001). CONCLUSIONS: First-year residents reported performing EPAs with less supervision than expected by CSs, especially during the night. Using EPAs to guide the content of the undergraduate curriculum and during examinations could help better align CSs' and residents' expectations about early residency supervision. PMID- 25113119 TI - What is the role of e-learning? Looking past the hype. PMID- 25113120 TI - Correction of the Scimitar syndrome, a rare cardiac venous anomaly, leading to Budd-Chiari syndrome: a case report. AB - INTRODUCTION: Scimitar syndrome is a congenital heart disease characterized by an abnormal drainage of the right lung into the inferior vena cava, the right atrium or a variety of venous connections from the anomalous pulmonary vein to a systemic vein. This left-to-right shunt induces pulmonary hypertension and is an indication for surgical repair in cases of a history of recurrent pneumonia or significant left-to-right shunting. A corrective approach, which consists of rerouting the anomalous pulmonary flow to the left atrium, is usually performed. Complications of scimitar repair are stenosis, thrombosis and occlusion of the scimitar vein and its deviation. CASE PRESENTATION: This case report describes a 53-year-old Caucasian woman with known scimitar syndrome, undergoing surgical repair due to invaliding symptoms of dyspnoea, and presenting with postoperative Budd-Chiari syndrome due to anomalous drainage of her right hepatic vein into the left atrium. It is an interesting cause of liver pathology caused by Budd-Chiari that never has been described before. CONCLUSIONS: This case report emphasizes the importance of a thorough preoperative evaluation, and the importance of antecedents in newly presenting pathology. It is an interesting cause of a known hepatic syndrome, the Budd-Chiari syndrome. This case report is of interest to many specialties, including Hepatology, Cardiology, Radiology and Cardiovascular Surgery. It exposes a new interesting anatomic variation of the scimitar syndrome with significant postoperative implications. PMID- 25113121 TI - Detection of antibodies against the CB9 to ICB10 region of merozoite surface protein-1 of Plasmodium vivax among the inhabitants in epidemic areas. AB - BACKGROUND: The purpose of this study was to examine the usefulness of the conserved block 9 (CB9) to interspecies conserved block (ICB10) region of Plasmodium vivax merozoite surface protein-1 (MSP-1 (ICB910)) as a serodiagnostic tool for understanding malaria transmission. METHODS: Antibody titre in the blood samples collected from the inhabitants of Gimpo city, Paju city and Yeoncheon county of Gyeonggi Province, as well as Cheorwon county of Gangwon Province, South Korea were determined by enzyme-linked immunosorbent assay (ELISA). Microscopic examination was performed to identify malarial parasites. RESULTS: MSP-1(ICB910) is encoded by a 1,212-bp sequence, which produced a recombinant protein with a molecular weight of approximately 46 kDa. Antibody titres in 1,774 blood samples were determined with the help of ELISA using purified recombinant MSP-1(ICB910). The overall ELISA-positive rate was 8.08% (n = 146). The annual parasite incidences (APIs) in the regions where the blood sampling was carried out gradually decreased from 2004 to 2005 (1.09 and 0.80, respectively). Yeoncheon county had the highest ELISA-positive rate (10.20%, 46/451). Yeoncheon county also had the highest API both in 2004 and 2005, followed by Cheorwon county, Paju city and Gimpo city. CONCLUSIONS: The MSP-1 (ICB910)-ELISA-positive rates were closely related to API in the geographic areas studied. These results suggest that sero-epidemiological studies employing MSP-1 (ICB910)-ELISA may be helpful in estimating the prevalence of malaria in certain geographic areas. MSP 1(ICB910)-ELISA can be effectively used to establish and evaluate malaria control and eradication programmes in the affected areas. PMID- 25113124 TI - Melatonin normalizes clinical and biochemical parameters of mild inflammation in diet-induced metabolic syndrome in rats. AB - The objective of this study was to evaluate the efficacy of melatonin to affect mild inflammation in the metabolic syndrome (MS) induced by a high-fat diet in rats. Adult Wistar male rats were divided into four groups (n = 16/group): (i) control diet (3% fat); (ii) high-fat (35%) diet; (iii) high-fat diet + melatonin; and (iv) melatonin. Rats had free access to high-fat or control chow and one of the following drinking solutions for 10 wk: (a) tap water; (b) 25 MUg/mL of melatonin. Plasma interleukin (IL)-1beta, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and C-reactive protein (CRP) were measured at two time intervals, that is, the middle of daylight period and the middle of the scotophase. In addition, a number of somatic and metabolic components employed clinically to monitor the MS were measured. Melatonin decreased the augmented circulating levels of IL-1beta, IL-6, TNF-alpha, IFN gamma, and CRP seen in obese rats and restored the depressed levels of IL-4 and IL-10. Rats fed with the high-fat diet showed significantly higher body weights and augmented systolic blood pressure from the third and fourth week onwards, respectively, melatonin effectively preventing these changes. In high-fat-fed rats, circulating low-density lipoprotein-cholesterol, total cholesterol, and triglyceride concentration augmented significantly, melatonin being effective to counteract these changes. Melatonin-treated rats showed a decreased insulin resistance, the highest values of plasma high-density lipoprotein-cholesterol, and the lowest values of plasma uric acid. The results indicate that melatonin is able to normalize the altered biochemical pro-inflammatory profile seen in rats fed with a high-fat diet. PMID- 25113123 TI - Ammonium increases Ca(2+) signalling and up-regulates expression of TRPC1 gene in astrocytes in primary cultures and in the in vivo brain. AB - Rapid rise in ammonium concentration in the brain is the major pathogenic factor in hepatic encephalopathy that is manifested by state of confusion, forgetfulness and irritability, psychotic symptoms, delusions, lethargy, somnolence and, in the terminal stages, coma. Primary cultures of mouse astrocytes were used to investigate effects of chronic treatment (3 days) with ammonium chloride (ammonium) at 3 mM, this being a relevant concentration for hepatic encephalopathy condition, on metabotropic receptor agonist-induced increases in free cytosolic Ca(2+) concentration [(Ca(2+))i], measured with fura-2 based microfluorimetry and on store-operated Ca(2+) entry (SOCE) activated following treatment with the SERCA inhibitor thapsigargin. The agonists used were the beta adrenergic agonist isoproterenol, the alpha2-adrenergic agonist dexmedetomidine, the InsP3 receptor (InsP3R) agonist adenophostin A and ryanodine receptor agonist 4-Chloro-m-cresol (4-CMC). Agonist-induced [Ca(2+)]i responses were significantly increased in astrocytes chronically exposed to ammonium. Similarly, the SOCE, meditated by the transient receptor potential channel 1 (TRPC1), was significantly augmented. The ammonium-induced increase in SOCE was a result of an up-regulation of mRNA and protein expression of TRPC1 in astrocytes. Increase in TRPC1 expression and in SOCE were both prevented by ouabain antagonist canrenone. Similar up-regulation of TRPC1 gene expression was found in the brain of adult mice subjected to intraperitoneal injection of urease for 3 days. In transgenic mice tagged with an astrocyte-specific or a neurone-specific markers and treated with intraperitoneal injections of urease for 3 days, the fluorescence-activated cell sorting of neurones and astrocytes demonstrated that TRPC1 mRNA expression was up-regulated in astrocytes, but not in neurones. PMID- 25113126 TI - Suppression of irrelevant activation in the horizontal and vertical Simon task differs quantitatively not qualitatively. AB - The Simon effect is usually explained by the assumption that the irrelevant stimulus location automatically activates the corresponding response. In the case of incongruent stimulus-response assignments automatically activated responses therefore have to be suppressed to ensure correct responses. This account, however, has been called into question for other than horizontally arranged visual Simon tasks. We investigated whether there is a qualitative or quantitative difference in suppression of irrelevant activation between horizontally and vertically arranged Simon tasks, using delta-function analyses. Sequential analyses revealed suppression after incongruent trials in both tasks, supporting the idea of a quantitative rather than a qualitative difference between the tasks. We conclude that automatic response activation is weaker in vertical tasks resulting in lower inhibitory demands as compared to horizontal tasks. PMID- 25113122 TI - Why are astrocytes important? AB - Astrocytes, which populate the grey and white mater of the brain and the spinal cord are highly heterogeneous in their morphology and function. These cells are primarily responsible for homeostasis of the central nervous system (CNS). Most central synapses are surrounded by exceedingly thin astroglial perisynaptic processes, which act as "astroglial cradle" critical for genesis, maturation and maintenance of synaptic connectivity. The perisynaptic glial processes are densely packed with numerous transporters, which provide for homeostasis of ions and neurotransmitters in the synaptic cleft, for local metabolic support and for release of astroglial derived scavengers of reactive oxygen species. Through perivascular processes astrocytes contribute to blood-brain barrier and form "glymphatic" drainage system of the CNS. Furthermore astrocytes are indispensible for glutamatergic and gamma-aminobutyrate-ergic synaptic transmission being the supplier of neurotransmitters precursor glutamine via an astrocytic/neuronal cycle. Pathogenesis of many neurological disorders, including neuropsychiatric and neurodegenerative diseases is defined by loss of homeostatic function (astroglial asthenia) or remodelling of astroglial homoeostatic capabilities. Astroglial cells further contribute to neuropathologies through mounting complex defensive programme generally known as reactive astrogliosis. PMID- 25113127 TI - The specificity of expertise: for whom is the clave pattern the "key" to salsa music? AB - Each Latin salsa music style is associated with a characteristic clave pattern that constitutes an essential structure for performers. In this article we asked what types of expertise are needed to detect the correct salsa-clave pairing. Using two clave patterns (the 3-2 and 2-3 son clave) and three manipulated alternatives, we asked listeners to choose the correct clave pattern for a variety of bomba, calypso, mambo and merengue excerpts. The results of Studies 1 and 2 show that listeners unfamiliar with salsa were unable to detect the correct salsa-clave pairing. Listeners who had some music training or were familiar with salsa detected the need for syncopation but not the specific pairing. Only musicians well-acquainted with salsa correctly detected the salsa-clave pairing. Studies 3 and 4 showed that incorrect choices were not due to an inability to distinguish between the alternatives: both adults and five-year-olds could easily tell apart the various patterns we used. We conclude that the distinction between the 2-3 and 3-2 claves is not inherent in the music itself, but rather is a convention to be learned through exposure and training. We discuss the results using an analogy to language learning. PMID- 25113125 TI - Single adatom dynamics at monatomic steps of free-standing few-layer reduced graphene. AB - Steps and their associated adatoms extensively exist and play prominent roles in affecting surface properties of materials. Such impacts should be especially pronounced in two-dimensional, atomically-thin membranes like graphene. However, how single adatom behaves at monatomic steps of few-layer graphene is still illusive. Here, we report dynamics of individual adatom at monatomic steps of free-standing few-layer reduced graphene under the electron beam radiations, and demonstrate the prevalent existence of monatomic steps even down to unexpectedly ultrasmall lateral size of a circular diameter of ~5 A. Single adatom prefers to stay at the edges of the atomic steps of few-layer reduced graphene and evolve with the steps. Moreover, we also find that how the single adatom behaves at atomic step edges can be remarkably influenced by the type of adatoms and step edges. Such single adatoms at monatomic steps and ultrasmall atomic steps open up a new window for surface physics and chemistry for graphene-based as well as other two-dimensional materials. PMID- 25113128 TI - Know thy sound: perceiving self and others in musical contexts. AB - This review article provides a summary of the findings from empirical studies that investigated recognition of an action's agent by using music and/or other auditory information. Embodied cognition accounts ground higher cognitive functions in lower level sensorimotor functioning. Action simulation, the recruitment of an observer's motor system and its neural substrates when observing actions, has been proposed to be particularly potent for actions that are self-produced. This review examines evidence for such claims from the music domain. It covers studies in which trained or untrained individuals generated and/or perceived (musical) sounds, and were subsequently asked to identify who was the author of the sounds (e.g., the self or another individual) in immediate (online) or delayed (offline) research designs. The review is structured according to the complexity of auditory-motor information available and includes sections on: 1) simple auditory information (e.g., clapping, piano, drum sounds), 2) complex instrumental sound sequences (e.g., piano/organ performances), and 3) musical information embedded within audiovisual performance contexts, when action sequences are both viewed as movements and/or listened to in synchrony with sounds (e.g., conductors' gestures, dance). This work has proven to be informative in unraveling the links between perceptual-motor processes, supporting embodied accounts of human cognition that address action observation. The reported findings are examined in relation to cues that contribute to agency judgments, and their implications for research concerning action understanding and applied musical practice. PMID- 25113129 TI - Emotion modulates allocentric but not egocentric stimulus localization: implications for dual visual systems perspectives. AB - Considerable evidence suggests that emotional cues influence processing prioritization and neural representations of stimuli. Specifically, within the visual domain, emotion is known to impact ventral stream processes and ventral stream-mediated behaviours; it remains unclear, however, the extent to which emotion impacts dorsal stream processes. In the present study, participants localized a visual target stimulus embedded within a background array utilizing allocentric localization (requiring an object-centred representation of visual space to perform an action) and egocentric localization (requiring purely target directed actions), which are thought to differentially rely on the ventral versus dorsal visual stream, respectively. Simultaneously, a task-irrelevant negative, positive or neutral sound was presented to produce an emotional context. In line with predictions, we found that during allocentric localization, response accuracy was enhanced in the context of negative compared to either neutral or positive sounds. In contrast, no significant effects of emotion were identified during egocentric localization. These results raise the possibility that negative emotional auditory contexts enhance ventral stream, but not dorsal stream, processing in the visual domain. Furthermore, this study highlights the complexity of emotion-cognition interactions, indicating how emotion can have a differential impact on almost identical overt behaviours that may be governed by distinct neurocognitive systems. PMID- 25113130 TI - Do the same genes underlie parallel phenotypic divergence in different Littorina saxatilis populations? AB - Parallel patterns of adaptive divergence and speciation are cited as powerful evidence for the role of selection driving these processes. However, it is often not clear whether parallel phenotypic divergence is underlain by parallel genetic changes. Here, we asked about the genetic basis of parallel divergence in the marine snail Littorina saxatilis, which has repeatedly evolved coexisting ecotypes adapted to either crab predation or wave action. We sequenced the transcriptome of snails of both ecotypes from three distant geographical locations (Spain, Sweden and United Kingdom) and mapped the reads to the L. saxatilis reference genome. We identified genomic regions potentially under divergent selection between ecotypes within each country, using an outlier approach based on F(ST) values calculated per locus. In line with previous studies indicating that gene reuse is generally common, we expected to find extensive sharing of outlier loci due to recent shared ancestry and gene flow between at least two of the locations in our study system. Contrary to our expectations, we found that most outliers were country specific, suggesting that much of the genetic basis of divergence is not shared among locations. However, we did find that more outliers were shared than expected by chance and that differentiation of shared outliers is often generated by the same SNPs. We discuss two mechanisms potentially explaining the limited amount of sharing we observed. First, a polygenic basis of divergent traits might allow for multiple distinct molecular mechanisms generating the same phenotypic patterns. Second, additional, location-specific axes of selection that we did not focus on in this study may produce distinct patterns of genetic divergence within each site. PMID- 25113131 TI - Very low rates of screening for metabolic syndrome among patients with severe mental illness in Durban, South Africa. AB - BACKGROUND: Sub Saharan African is experiencing the largest increase in the prevalence of type 2 diabetes mellitus and cardiovascular disease globally. Metabolic syndrome (MetS) is a cluster of risk factors for these conditions. There is a consistently higher prevalence of cardiometabolic disease among individuals with severe mental illness (SMI) compared to the general population worldwide. However, it is known from research in high income countries that screening for MetS in patients with SMI is low. The objective of this study was to document the extent of the expected low frequency of testing for all the components of the metabolic syndrome (MetS) in patients with SMI in a low middle income country. METHODS: This was a cross sectional study, undertaken from January to June 2012 on out-patients with SMI who were treated with antipsychotic medication for at least 6 months. The study measured the proportion of participants who were tested for MetS in the previous year. RESULTS: The study included 331 (M: F; 167:164) participants with a mean age of 35.2 +/- 11.98 years. The majority (78.8%) were black South Africans. Only 2 subjects (0.6%) were screened for all five components of MetS. Regarding the individual components, 99%, 0.6%, 3.9% and 1.8% were screened for raised blood pressure, abdominal obesity, hyperglycaemia, hypertriglyceridaemia and decreased high density lipoprotein cholesterol respectively. CONCLUSION: It is unacceptable that less than one percent of our participants were adequately screened for modifiable risk factors for type 2 diabetes mellitus and cardiovascular disease which are the most common causes of mortality among patients with SMI. These results highlight the need for translating guidelines into action in low and middle income countries. PMID- 25113132 TI - Incidence and correlates of hepatitis C virus infection in a large cohort of prisoners who have injected drugs. AB - BACKGROUND: Hepatitis C virus (HCV) infection is common among prisoners, particularly those with a history of injecting drug use (IDU). Incarcerated people who inject drugs frequently report high-risk injecting practices both in prison and in the community. In spite of rising morbidity and mortality, utilisation of HCV-related services in Australia has been persistently low. This study aimed to describe the incidence, prevalence and correlates of HCV seropositivity in a large cohort of prisoners who have injected drugs, and to identify correlates of receiving confirmation of active infection. METHODS: Data linkage to a State-wide statutory notifiable diseases surveillance system was used to investigate the incidence of notified HCV seropositivity, seroconversion and confirmed HCV infection in a cohort of 735 prisoners with a history of IDU, over 14 years of follow up. Hepatitis C test results from prison medical records were used to identify correlates of testing positive in prison. RESULTS: The crude incidence of HCV notification was 5.1 cases per 100 person-years. By the end of follow up, 55.1% of the cohort had been the subject of a HCV-related notification, and 47.4% of those tested in prison were HCV seropositive. In multivariable analyses, injecting in prison was strongly associated with HCV seropositivity, as was opioid use compared to injection of other drugs. The rate of reported diagnostic confirmation among those with notified infections was very low, at 6.6 confirmations per 100 seropositive participants per year. CONCLUSIONS: Injecting drugs in prison was strongly associated with HCV seropositivity, highlighting the need for increased provision of services to mitigate the risk of transmission within prisons. Once identified as seropositive through screening, people with a history of IDU and incarceration may not be promptly receiving diagnostic services, which are necessary if they are to access treatment. Improving access to HCV-related services will be of particular importance in the coming years, as HCV-related morbidity and mortality is increasing, and next generation therapies are becoming more widely available. PMID- 25113133 TI - The antidiabetic agent glibenclamide protects airway hyperresponsiveness and inflammation in mice. AB - Glibenclamide has a newly discovered role in inflammation regulation besides its antidiabetic effect. As an inhibitor of ATP-sensitive potassium (KATP) channel, glibenclamide antagonizes the relaxation of the tracheal smooth muscle. This indicates that glibenclamide might attenuate airway inflammation while aggravate airway hyperresponsiveness (AHR) in asthmatics. Clinically, many diabetics with asthma are prescribed with glibenclamide to control blood glucose. However, whether glibenclamide could exert any effects on asthmatic inflammation remains unknown. Using an ovalbumin (OVA)-induced mouse model of asthma, we evaluated the effects of glibenclamide on the AHR and inflammation. Interestingly, glibenclamide reduced all the cardinal features of asthma in OVA-challenged mice, including AHR, airway inflammation, and T-helper type 2 (Th2) cytokines. Glibenclamide also downregulated OVA-induced expressions of vascular cell adhesion molecule 1 (VCAM-1) and phosphorylated signal transducer and activator of transcription 6 (p-STAT6) in the lung. In addition, increased sulfonylurea receptor 1 (SUR1) expression in the lung was observed after the OVA challenge. These findings suggest that the classic sulfonylurea glibenclamide plays an important protective role in the development of asthma, which not only provides the evidence for the safety of prescribed glibenclamide in diabetics combined with asthma but also indicates a possible new therapeutic for asthma via targeting glibenclamide-related pathways. PMID- 25113134 TI - Human leukocyte antigen DR surface expression on CD14+ monocytes during adverse events after hematopoietic stem cell transplantation. AB - The human leukocyte antigen DR surface expression on CD14+ monocytes reflects the degree to which these cells have been activated. Given the central role monocytes and macrophages play in the immune system, a decreased human leukocyte antigen DR expression on CD14+ monocytes results in a hallmark of altered immune status during systemic inflammatory response syndrome. We hypothesize that human leukocyte antigen DR expression might be similarly altered after hematopoietic stem cell transplantation and during post-transplant complications. Using flow cytometry, this study investigates the human leukocyte antigen DR surface expression of CD14+ monocytes in 30 pediatric and young adult patients up to 1 year after hematopoietic stem cell transplantation. Normal values were derived from a control group of healthy children, adolescents, and young adults. Human leukocyte antigen DR expression decreased significantly prior and during bacterial infection or sepsis. By contrast, human leukocyte antigen DR expression levels were elevated before and at the time of viremia. Human leukocyte antigen DR expression was also elevated during acute graft-versus-host disease. In contrast, the expression was reduced when patients had hepatic veno-occlusive disease. A significant decrease of human leukocyte antigen DR expression was associated with a relapse of the underlying disease and before death. Human leukocyte antigen DR expression on CD14+ monocytes appears to be a promising parameter that might allow identification of patients at risk after hematopoietic stem cell transplantation. PMID- 25113135 TI - An automatic patient-specific seizure onset detection method using intracranial electroencephalography. AB - OBJECTIVE: This study presents a multichannel patient-specific seizure detection method based on the empirical mode decomposition (EMD) and support vector machine (SVM) classifier. MATERIALS AND METHODS: The EMD is used to extract features from intracranial electroencephalography (EEG). A machine-learning algorithm is used as a classifier to discriminate between seizure and nonseizure intracranial EEG epochs. A postprocessing algorithm is proposed to reject artifacts and increase the robustness of the method. The proposed method was evaluated using 463 hours of intracranial EEG recordings from 17 patients with a total of 51 seizures in the Freiburg EEG database. RESULTS: The proposed method had better performance than most of the existing seizure detection systems, including an average sensitivity of 92%, false detection rate (FDR) of 0.17/hour, and time delay (TD) of 12 sec. Moreover, the FDR could be further reduced by a TD extension. CONCLUSIONS: Given its high sensitivity and low FDR, the proposed patient specific seizure detection method can greatly assist clinical staff with automatically marking seizures in long-term EEG or detecting seizure onset online with high performance. Early and accurate seizure detection using this method may serve as a practical tool for planning epilepsy interventions. PMID- 25113137 TI - Metastable ionic diodes derived from an amine-based polymer of intrinsic microporosity. AB - A highly rigid amine-based polymer of intrinsic microporosity (PIM), prepared by a polymerization reaction involving the formation of Troger's base, is demonstrated to act as an ionic diode with electrolyte-dependent bistable switchable states. PMID- 25113136 TI - Effects of sigh during pressure control and pressure support ventilation in pulmonary and extrapulmonary mild acute lung injury. AB - INTRODUCTION: Sigh improves oxygenation and lung mechanics during pressure control ventilation (PCV) and pressure support ventilation (PSV) in patients with acute respiratory distress syndrome. However, so far, no study has evaluated the biological impact of sigh during PCV or PSV on the lung and distal organs in experimental pulmonary (p) and extrapulmonary (exp) mild acute lung injury (ALI). METHODS: In 48 Wistar rats, ALI was induced by Escherichia coli lipopolysaccharide either intratracheally (ALIp) or intraperitoneally (ALIexp). After 24 hours, animals were anesthetized and mechanically ventilated with PCV or PSV with a tidal volume of 6 mL/kg, FiO2 = 0.4, and PEEP = 5 cmH2O for 1 hour. Both ventilator strategies were then randomly assigned to receive periodic sighs (10 sighs/hour, Sigh) or not (non-Sigh, NS). Ventilatory and mechanical parameters, arterial blood gases, lung histology, interleukin (IL)-1beta, IL-6, caspase-3, and type III procollagen (PCIII) mRNA expression in lung tissue, and number of apoptotic cells in lung, liver, and kidney specimens were analyzed. RESULTS: In both ALI etiologies: (1) PCV-Sigh and PSV-Sigh reduced transpulmonary pressure, and (2) PSV-Sigh reduced the respiratory drive compared to PSV-NS. In ALIp: (1) PCV-Sigh and PSV-Sigh decreased alveolar collapse as well as IL-1beta, IL-6, caspase-3, and PCIII expressions in lung tissue, (2) PCV-Sigh increased alveolar-capillary membrane and endothelial cell damage, and (3) abnormal myofibril with Z-disk edema was greater in PCV-NS than PSV-NS. In ALIexp: (1) PSV Sigh reduced alveolar collapse, but led to damage to alveolar-capillary membrane, as well as type II epithelial and endothelial cells, (2) PCV-Sigh and PSV-Sigh increased IL-1beta, IL-6, caspase-3, and PCIII expressions, and (3) PCV-Sigh increased the number of apoptotic cells in the lung compared to PCV-NS. CONCLUSIONS: In these models of mild ALIp and ALIexp, sigh reduced alveolar collapse and transpulmonary pressures during both PCV and PSV; however, improved lung protection only during PSV in ALIp. PMID- 25113138 TI - Increasing childhood influenza vaccination: a cluster randomized trial. AB - BACKGROUND: Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. PURPOSE: To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. METHODS: In 2011-2012, a total of 20 primary care practices treating children were randomly assigned to the intervention and control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. RESULTS: The average vaccination differences from pre-intervention to the intervention year were significantly larger in the intervention arm (n=10 practices) than the control arm (n=10 practices); for children aged 9-18 years (11.1 pct pts intervention vs 4.3 pct pts control, p<0.05); for non-white children (16.7 pct pts intervention vs 4.6 pct pts control, p<0.001); and overall (9.9 pct pts intervention vs 4.2 pct pts control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race, and intervention, the likelihood of vaccination increased with younger age group (6-23 months); white race; commercial insurance; the practice's pre intervention vaccination rate; and being in the intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9-18 years. CONCLUSIONS: A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza vaccination uptake across age and racial groups without targeting specific groups, especially in practices with large percentages of minority children. PMID- 25113139 TI - Motivational counseling to reduce sitting time: a community-based randomized controlled trial in adults. AB - BACKGROUND: Sedentary behavior is regarded as a distinct risk factor for cardiometabolic morbidity and mortality, but knowledge of the efficacy of interventions targeting reductions in sedentary behavior is limited. PURPOSE: To investigate the effect of an individualized face-to-face motivational counseling intervention aimed at reducing sitting time. DESIGN: A randomized, controlled, observer-blinded, community-based trial with two parallel groups using open-end randomization with 1:1 allocation. SETTING/PARTICIPANTS: A total of 166 sedentary adults were consecutively recruited from the population-based Health2010 Study. INTERVENTION: Participants were randomized to a control (usual lifestyle) or intervention group with four individual theory-based counseling sessions. MAIN OUTCOME MEASURES: Objectively measured overall sitting time (ActivPAL 3TM, 7 days); secondary measures were breaks in sitting time, anthropometric measures, and cardiometabolic biomarkers, assessed at baseline and after 6 months. Data were collected in 2010-2012 and analyzed in 2013-2014 using repeated measures multiple regression analyses. RESULTS: Ninety-three participants were randomized to the intervention group and 73 to the control group, and 149 completed the study. The intervention group had a mean sitting time decrease of -0.27 hours/day, corresponding to 2.9% of baseline sitting time (hours/day); the control group increased mean sitting time by 0.06 hours/day. The between-group difference in change, -0.32 hours/day (95% CI=-0.87, 0.24, p=0.26), was not statistically significant. Significant differences in change in fasting serum insulin of -5.9 pmol/L (95% CI=-11.4, -0.5, p=0.03); homeostasis model assessment estimated insulin resistance of -0.28 (95% CI=-0.53, -0.03, p=0.03); and waist circumference of -1.42 cm (95% CI=-2.54, -0.29, p=0.01) were observed in favor of the intervention group. CONCLUSIONS: Although the observed decrease in sitting time was not significant, a community-based, individually tailored, theory-based intervention program aimed at reducing sitting time may be effective for increasing standing and improving cardiometabolic health in sedentary adults. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov (NCT00289237). PMID- 25113141 TI - FDA allows second experimental drug to be tested in Ebola patients. PMID- 25113140 TI - Oestradiol modulates the effects of leptin on energy homeostasis by corticotrophin-releasing factor type 2 receptor. AB - In addition to its action in the control of the hypothalamic-pituitary-adrenal axis, corticotrophin-releasing factor (CRF) has been described as an anorexigenic neuropeptide, modulating food intake and energy expenditure. CRF synthesis is influenced by leptin, which would act to increase CRF neurone activation in the paraventricular nucleus (PVN). Gonadal hormones also participate in the regulation of energy homeostasis. The reduction of food intake and body weight gain in ovariectomised (OVX) rats treated with oestradiol is associated with an increase in CRF mRNA expression in the PVN. The present study aimed to investigate the role of CRF as a mediator of leptin responsiveness in the presence of oestradiol. Wistar female rats were bilaterally OVX and divided into three groups: OVX, OVX+E (i.e. treated with oestradiol) and OVX+PF (i.e. OVX pairfed with OVX+E). The rats received daily s.c. injections of either oestradiol cypionate or vehicle for 8 days. To evaluate the role of CRF on the effects of leptin, we performed an i.c.v. leptin injection (10 MUg/5 MUl) with or without previous i.c.v. treatment with an CRF-R2 antagonist. We observed that oestradiol replacement in OVX rats reduced body weight gain and food intake. The effects of exogenous leptin administration with respect to decreasing food intake and body weight, and increasing uncoupling protein-1 expression in the brown adipose tissue and neuronal activation in the arcuate nucleus, were reversed by previous administration of a CRF-R2 antagonist only in oestradiol-treated OVX rats. These effects appear to be mediated by CRF-2 receptor because the antagonist of this receptor reversed the action of oestradiol on the effects of leptin. PMID- 25113142 TI - Epithelial-mesenchymal transition as a fundamental underlying pathogenic process in COPD airways: fibrosis, remodeling and cancer. AB - Chronic obstructive pulmonary disease (COPD) is a complex condition, frequently with a mix of airway and lung parenchymal damage. However, the earliest changes are in the small airways, where most of the airflow limitation occurs. The pathology of small airway damage seems to be wall fibrosis and obliteration, but the whole airway is involved in a 'field effect'. Our novel observations on active epithelial-mesenchymal transition (EMT) in the airways of smokers, particularly in those with COPD, are changing the understanding of this airway pathology and the aetiology of COPD. EMT involves a cascade of regulatory changes that destabilise the epithelium with a motile and mesenchymal epithelial cell phenotype emerging. One important manifestation of EMT activity involves up regulation of specific key transcription factors (TFs), such as Smads, Twist, and beta-catenin. Such TFs can be used as EMT biomarkers, in recognisable patterns reflecting the potential major drivers of the process; for example, TGFbeta, Wnt, and integrin-linked kinase systems. Thus, understanding the relative changes in TF activity during EMT may provide rich information on the mechanisms driving this whole process, and how they may change over time and with therapy. We have sought to review the current literature on EMT and the relative expression of specific TF activity, to define the networks likely to be involved in a similar process in the airways of patients with smoking-related COPD. PMID- 25113143 TI - A novel KIR2DL3 variant allele, KIR2DL3*031, identified from a southern Chinese Han individual. AB - The novel KIR2DL3*031 allele differs from KIR2DL3*00101 by a synonymous mutation and a non-synonymous mutation. PMID- 25113144 TI - Spontaneous passage of a very large ureteral stone. PMID- 25113145 TI - Evaluation of antimicrobial treatment in a bovine model of acute Chlamydia psittaci infection: tetracycline versus tetracycline plus rifampicin. AB - Antimicrobial treatment of chlamydial infections is known to be of limited efficacy. In this study, effects of doxycycline (D), usually the drug of choice, were compared with the combined therapy of doxycycline and rifampicin (R) in a bovine model of respiratory Chlamydia psittaci infection. After intrabronchial inoculation of the pathogen, 30 animals were assigned to five groups (n = 6 per group): untreated controls, monotherapy with D (5 mg kg(-1)day(-1) or 10 mg kg( 1)day(-1)), and combination therapy of D and R (600 mg day(-1)). Treatment continued until day 14 post inoculation (d.p.i.). Clinical signs, inflammatory markers, and pathological findings confirmed successful infection in all animals. Reisolation of the pathogen was possible in 4/6 untreated animals and in 4/12 animals treated with D alone until 4 d.p.i., but in none of the calves of the two D + R groups. Pathogen detection was possible in all animals without significant differences among groups. Severity of disease and time course of its resolution, assessed by clinical and pathological findings as well as inflammatory parameters, were not significantly different between untreated controls and calves receiving D alone or in combination with R. Regardless of the treatment regimen, all groups recovered clinically and cleared the infection within 2 weeks. PMID- 25113146 TI - Optimization of culturing conditions for toxicity testing with the alga Oophila sp. (Chlorophyceae), an amphibian endosymbiont. AB - Eggs of the yellow-spotted salamander (Ambystoma maculatum) have a symbiotic relationship with green algae. It has been suggested that contaminants that are preferentially toxic to algae, such as herbicides, may impair the symbiont and, hence, indirectly affect the development of the salamander embryo. To enable testing under near-standard conditions for first-tier toxicity screening, the authors isolated the alga from field-collected eggs and identified conditions providing exponential growth rates in the apparent asexual phase of the alga. This approach provided a uniform, single-species culture, facilitating assessment of common toxicity end points and comparison of sensitivity relative to other species. Sequencing of the 18s ribosomal DNA indicated that the isolated alga is closely related to the recently described Oophila amblystomatis but is more similar to other known Chlamydomonas species, suggesting possible biogeographical variability in the genetic identity of the algal symbiont. After a tiered approach to culturing method refinement, a modified Bristol's media with 1 mM NH4 (+) as nitrogen source was found to provide suitable conditions for toxicity testing at 18 degrees C and 200 umol m(-2) s(-1) photosynthetically active radiation (PAR) on a 24-h light cycle. The validity of the approach was demonstrated with Zn(2+) as a reference toxicant. Overall, the present study shows that screening for direct effects of contaminants on the algal symbiont without the presence of the host salamander is possible under certain laboratory conditions. PMID- 25113147 TI - Mother-child interactions in the NICU: relevance and implications for later parenting. AB - OBJECTIVE: This study examined the feasibility of observing mother-child interactions in the neonatal intensive care unit (NICU), whether NICU interactions related to later interactions, and how interactions related to child and maternal characteristics. METHODS: The sample included 130 preterm infants and their mothers, observed in a feeding interaction in the NICU. Dyads were observed through 36 months postterm. RESULTS: Observed maternal positive affective involvement and verbalizations in the NICU were associated with the same parenting behaviors at 24 months, social support, socioeconomic status, and being born in the late preterm period. Maternal negative affect and behavior were unrelated to later maternal negativity or child and maternal characteristics. CONCLUSIONS: Positive parenting assessed in the NICU appears related to later parenting interaction quality, suggesting early assessment is possible. Maternal negative affect and behavior toward children may not consistently emerge until later in development. PMID- 25113148 TI - Evaluation of regional cerebral glucose metabolism in patients with malignant lymphoma of the body using statistical image analysis. AB - OBJECTIVES: The aim of this study was to clarify the characteristics of regional cerebral glucose metabolic abnormalities in patients with malignant lymphoma of the body using statistical image analyses. Post-therapeutic changes in cerebral glucose metabolism were also evaluated. METHODS: The subjects consisted of 30 patients, including 16 patients with diffuse large B-cell lymphoma and 14 patients with other types of lymphoma. Patients with primary cerebral lymphoma were excluded from this study. All patients underwent CT and whole-body FDG-PET scans, including 4-min brain scans using a dedicated PET/CT scanner during both the pre- and post-treatment periods. The whole-body scans started 60 min after the administration of 185 MBq of FDG, after which the brain data were extracted from whole-body data. The degree of regional cerebral glucose metabolism was evaluated on a voxel-by-voxel basis using statistical parametric mapping (SPM). The total tumor glycolytic volume of the body was measured using a separate workstation. The normal control subjects were 12 persons who underwent medical check with FDG-PET/CT and had no lesions suggesting malignant tumor. RESULTS: The level of regional cerebral glucose metabolism decreased in association with an increase in the total glycolytic volume in the bilateral frontal and parietal cortices. After chemotherapy, the statistical image analysis demonstrated an interval recovery of the cerebral glucose metabolism of the bilateral parietal and occipital cortices in the good responders, whereas there were no significant differences observed in regional cerebral glucose metabolism between the pre- and post-treatment images in the poor responders. Comparison between normal control subjects and patients with pre-treatment lymphoma also showed that the regional cerebral glucose metabolism decreased in the parieto-occipital cortices in patients with lymphoma compared to normal control subjects. CONCLUSIONS: We demonstrated that patients with malignant lymphoma of the body exhibited abnormal regional cerebral glucose metabolism, which improves after chemotherapy. Although the mechanism underlying the reduction of cerebral glucose metabolism remains unclear, our findings indicate the functional alternation and/or subclinical damage of the brain in patients with malignant lymphoma. PMID- 25113149 TI - Nuclear medicine practice in Japan: a report of the seventh nationwide survey in 2012. AB - OBJECTIVE: The Subcommittee on the Survey of Nuclear Medical Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years. METHODS: The subcommittee sent questionnaires, including the number and category of examinations as well as the kind and dose of the radiopharmaceuticals during the 30 days of June 2012, to all the nuclear medicine institutes. The total numbers for the year 2012 were then estimated. RESULTS: A total of 1,167 institutes responded to the survey, including the 14 in vitro assay institutes and 266 PET centers. The recovery rate was 92 %. The number of gamma cameras installed was 1,425 in total, with 9 % decrease in 5 years. Dual head cameras and hybrid SPECT/CT scanners accounted for 84 and 10.5 %, respectively. The number of single-photon tracer studies in 2012 was 1.15 million which means decrease in 19 % in 5 years and 29 % in 10 years. All but cerebral perfusion study and sentinel lymphoscintigraphy have decreased. Bone scintigraphy was a leading examination (38.7 %), followed by cardiac studies (29.4 %) and cerebral perfusion study (18.5 %) in order. SPECT studies showed an increase from 42.3 to 47.2 %. PET centers have also increased from 212 to 295, as compared to the last survey. The 135 PET centers have installed one or two in-house cyclotrons. PET studies showed 25.5 % increase in 5 years, with oncology accounting for 96.3 %. (18)F-FDG accounted for 98.2 % (505,990 examinations). PET examinations using (11)C-methionine have been increasing, with 3,352 examinations in 2012. The number of new PET studies using (11)C-PIB PET was 695. (131)I radioiodine targeted therapies showed an increase, including 3,644 patients (53.6 %) for thyroid cancer and 4,889 patients (17.9 %) for hyperthyroidism. Out patient thyroid bed ablation therapy with 30 mCi of (131)I accounted for 21.0 % of cancer patients. The number of admission rooms decreased from 158 to 135 in 5 years. In vitro radioassays have been declining continuously since 1992, with the number of studies of 9.0 million in 2012. CONCLUSIONS: Single-photon examinations showed a continuous tendency toward a decline in the survey. In contrast, the number of hybrid SPECT/CT scanner examinations has increased. PET/CT study in the oncology field and radionuclide targeted therapy have steadily increased. PMID- 25113151 TI - One-year outcomes associated with using observation services in triaging patients with nonspecific chest pain. AB - BACKGROUND: Observation services are provided in greatly variant settings. The aim of this study was to reexamine the effectiveness of observation services compared to inpatient units for patients with nonspecific chest pain. HYPOTHESIS: Patients admitted to observation units have similar outcomes to patients admitted to inpatient wards. METHODS: We conducted a claim-based retrospective study for 7549 patients who were admitted to observation and inpatient units. Both models of care were evaluated using the 1-year costs related to chest pain/cardiovascular diseases, and primary and secondary outcomes. Primary outcome was a composite of myocardial infarction, congestive heart failure, stroke, or cardiac arrest, whereas secondary outcomes included revascularization procedures, emergency room revisits, and hospitalization due to cardiovascular diseases. RESULTS: Two-thirds (65.7%, n = 4962) of patients in the sample had observation services, and 34.3% (n = 2587) were admitted to inpatient care. Of the inpatient group, 4.9% experienced a total of 167 primary outcomes, whereas 14.1% experienced a total of 571 secondary outcomes. In comparison, 3.8% of the observation group experienced 238 primary outcomes, and 10.3% experienced 737 secondary outcomes. After adjusting for baseline characteristics using Cox proportional hazard and quantile regression models, no differences between the 2 groups were detected in the 1-year costs of cardiovascular services and primary or secondary outcomes. Patients who had observation services were 79% (95% confidence interval: 1.24-2.58) more likely to have revascularization procedures compared to those admitted to inpatient care. CONCLUSIONS: Patients who had observation services had similar outcomes and 1-year costs compared to patients admitted to inpatient wards. PMID- 25113150 TI - UTIs in patients with neurogenic bladder. AB - Urinary tract infections (UTI) remain one of the most prevalent and frustrating morbidities for neurogenic bladder patients, and death attributed to urosepsis in the spinal cord injury (SCI) patient is higher when compared to the general population. Risk factors include urinary stasis, high bladder pressures, bladder stones, and catheter use. While classic symptoms of UTI include dysuria, increased frequency and urgency, neurogenic bladder patients present differently with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague pains. Multiple modalities have been assessed for prevention including catheter type, oral supplements, bladder irrigation, detrusor injections and prophylactic antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation with iAluRil((r)), detrusor injections, and weekly prophylaxis with alternating antibiotics appear to have a positive reduction in UTI but require further study. Ultimately, treatment for symptomatic UTI should account for the varied flora and possible antibiotic resistances including relying on urine cultures to guide antibiotic therapy. PMID- 25113153 TI - Representing and decomposing neural potential signals. AB - This paper reviews methodologies for analyzing neural potentials via frequency, time-frequency, or wavelet representations, and adaptive models that estimate the signal's spatial or temporal structure. The fundamental assumptions of each method are discussed. In particular, the Fourier transform is contrasted with overcomplete representations, which are able to precisely delineate the timing and/or frequency of neural events. Finally, a novel approach that combines overcomplete representations with adaptive signal models is presented. This approach describes a continuous signal as a linear combination of reoccurring waveforms, referred to as phasic events, which are often associated with neural processing. The new methodology automatically learns the reoccurring waveforms and quantifies the neural potentials by the set of amplitudes and timings. PMID- 25113152 TI - Health-related media use among youth audiences in Senegal. AB - Lower- and middle-income countries (LMICs) are experiencing rapid changes in access to and use of new internet and digital media technologies. The purpose of this study was to better understand how younger audiences are navigating traditional and newer forms of media technologies, with particular emphasis on the skills and competencies needed to obtain, evaluate and apply health-related information, also defined as health and media literacy. Sixteen focus group discussions were conducted throughout Senegal in September 2012 with youth aged 15-25. Using an iterative coding process based on grounded theory, four themes emerged related to media use for health information among Senegalese youth. They include the following: (i) media utilization; (ii) barriers and conflicts regarding media utilization; (iii) uses and gratifications and (iv) health and media literacy. Findings suggest that Senegalese youth use a heterogeneous mix of media platforms (i.e. television, radio, internet) and utilization often occurs with family members or friends. Additionally, the need for entertainment, information and connectedness inform media use, mostly concerning sexual and reproductive health information. Importantly, tensions arise as youth balance innovative and interactive technologies with traditional and conservative values, particularly concerning ethical and privacy concerns. Findings support the use of multipronged intervention approaches that leverage both new media, as well as traditional media strategies, and that also address lack of health and media literacy in this population. Implementing health-related interventions across multiple media platforms provides an opportunity to create an integrated, as opposed to a disparate, user experience. PMID- 25113155 TI - Why should working memory be related to incidentally learned sequence structures? PMID- 25113156 TI - A biomimetic multi-stimuli-response ionic gate using a hydroxypyrene derivation functionalized asymmetric single nanochannel. AB - A highly efficient multi-stimuli-response ionic gate that can be activated separately or cooperatively by pH and UV light has been demonstrated by modifying the environmental stimuli-responsive molecule 8-hydroxypyrene-1,3,6-trisulfonate into a track-etched single conical nanochannel. Such a multi-response ionic gate can find applications in areas such as electronics, actuators, and biosensors. PMID- 25113154 TI - Intracranial recordings and human memory. AB - Recent work involving intracranial recording during human memory performance provides superb spatiotemporal resolution on mnemonic processes. These data demonstrate that the cortical regions identified in neuroimaging studies of memory fall into temporally distinct networks and the hippocampal theta activity reported in animal memory literature also plays a central role in human memory. Memory is linked to activity at multiple interacting frequencies, ranging from 1 to 500Hz. High-frequency responses and coupling between different frequencies suggest that frontal cortex activity is critical to human memory processes, as well as a potential key role for the thalamus in neocortical oscillations. Future research will inform unresolved questions in the neuroscience of human memory and guide creation of stimulation protocols to facilitate function in the damaged brain. PMID- 25113157 TI - The many generations of sequencing technology. PMID- 25113160 TI - Sequence-based prediction of protein-binding sites in DNA: comparative study of two SVM models. AB - As many structures of protein-DNA complexes have been known in the past years, several computational methods have been developed to predict DNA-binding sites in proteins. However, its inverse problem (i.e., predicting protein-binding sites in DNA) has received much less attention. One of the reasons is that the differences between the interaction propensities of nucleotides are much smaller than those between amino acids. Another reason is that DNA exhibits less diverse sequence patterns than protein. Therefore, predicting protein-binding DNA nucleotides is much harder than predicting DNA-binding amino acids. We computed the interaction propensity (IP) of nucleotide triplets with amino acids using an extensive dataset of protein-DNA complexes, and developed two support vector machine (SVM) models that predict protein-binding nucleotides from sequence data alone. One SVM model predicts protein-binding nucleotides using DNA sequence data alone, and the other SVM model predicts protein-binding nucleotides using both DNA and protein sequences. In a 10-fold cross-validation with 1519 DNA sequences, the SVM model that uses DNA sequence data only predicted protein-binding nucleotides with an accuracy of 67.0%, an F-measure of 67.1%, and a Matthews correlation coefficient (MCC) of 0.340. With an independent dataset of 181 DNAs that were not used in training, it achieved an accuracy of 66.2%, an F-measure 66.3% and a MCC of 0.324. Another SVM model that uses both DNA and protein sequences achieved an accuracy of 69.6%, an F-measure of 69.6%, and a MCC of 0.383 in a 10-fold cross validation with 1519 DNA sequences and 859 protein sequences. With an independent dataset of 181 DNAs and 143 proteins, it showed an accuracy of 67.3%, an F measure of 66.5% and a MCC of 0.329. Both in cross-validation and independent testing, the second SVM model that used both DNA and protein sequence data showed better performance than the first model that used DNA sequence data. To the best of our knowledge, this is the first attempt to predict protein-binding nucleotides in a given DNA sequence from the sequence data alone. PMID- 25113158 TI - Safety and efficacy of triple therapy with peginterferon, ribavirin and boceprevir within an early access programme in Spanish patients with hepatitis C genotype 1 with severe fibrosis: SVRw12 analysis. AB - BACKGROUND & AIMS: The addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection. METHODS: Prospective, multicentre, national registry that includes naive and treatment-experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics. RESULTS: Most of the patients (68.2%) were male, with a mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load of 6.2 log. According to prior treatment, 20% of patients were treatment-naive and 80% had received prior treatment. Approximately 36.5% of patients (n = 62) reported at least one serious adverse events (SAEs) (total SAEs = 103). The most common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia (25.9%). Patients with albumin <3.5 g/dl and bilirubin >2 mg/dl had an increased relative risk (greater than one-fold) for SAEs, including infections and hepatic decompensation. In the intent-to-treat analysis (n = 170), the overall percentage of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4 (lead-in phase), the overall SVRw12 rate was 67.0%. In the patients initiating triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In a multivariate analysis, an increased probability of achieving SVR was associated with response to prior treatment (relapsers), >1 log decrease in viral load in the lead-in phase and baseline albumin >3.5 g/dl. CONCLUSIONS: Triple therapy in patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE and a lower rate in comparison with patients with mild disease. However, for patients with intact liver function, it could be considered as a treatment option, when other alternatives would not be available. PMID- 25113162 TI - Compliance, concordance and adherence: what are we talking about? AB - Adherence or compliance to prescribed treatment regimens is an important and much debated area of haemophilia care. Many patients are labelled as 'non-adherent' because they don't do what we say in terms of self- treatment and factor administration. However, do we engage patients in developing mutually acceptable treatment programmes which work for them as individuals? If we do, does this affect self-care and treatment uptake through a supportive relationship which enhances treatment concordance? Once we have agreed treatment regimens, how do we measure the success or outcomes of them? This paper discusses these issues, and some of the tools that are available to assess adherence in a systematic way. PMID- 25113159 TI - Hydrogen sulphide triggers VEGF-induced intracellular Ca2+ signals in human endothelial cells but not in their immature progenitors. AB - Hydrogen sulphide (H2S) is a newly discovered gasotransmitter that regulates multiple steps in VEGF-induced angiogenesis. An increase in intracellular Ca(2+) concentration ([Ca(2+)]i) is central to endothelial proliferation and may be triggered by both VEGF and H2S. Albeit VEGFR-2 might serve as H2S receptor, the mechanistic relationship between VEGF- and H2S-induced Ca(2+) signals in endothelial cells is unclear. The present study aimed at assessing whether and how NaHS, a widely employed H2S donor, stimulates pro-angiogenic Ca(2+) signals in Ea.hy926 cells, a suitable surrogate for mature endothelial cells, and human endothelial progenitor cells (EPCs). We found that NaHS induced a dose-dependent increase in [Ca(2+)]i in Ea.hy926 cells. NaHS-induced Ca(2+) signals in Ea.hy926 cells did not require extracellular Ca(2+) entry, while they were inhibited upon pharmacological blockade of the phospholipase C/inositol-1,4,5-trisphosphate (InsP3) signalling pathway. Moreover, the Ca(2+) response to NaHS was prevented by genistein, but not by SU5416, which selectively inhibits VEGFR-2. However, VEGF-induced Ca(2+) signals were suppressed by dl-propargylglycine (PAG), which blocks the H2S-producing enzyme, cystathionine gamma-lyase. Consistent with these data, VEGF-induced proliferation and migration were inhibited by PAG in Ea.hy926 cells, albeit NaHS alone did not influence these processes. Conversely, NaHS elevated [Ca(2+)]i only in a modest fraction of circulating EPCs, whereas neither VEGF-induced Ca(2+) oscillations nor VEGF-dependent proliferation were affected by PAG. Therefore, H2S-evoked elevation in [Ca(2+)]i is essential to trigger the pro-angiogenic Ca(2+) response to VEGF in mature endothelial cells, but not in their immature progenitors. PMID- 25113163 TI - Dramatic efficacy of brentuximab vedotin in two patients with epidermotropic cutaneous T-cell lymphomas after treatment failure despite variable CD30 expression. PMID- 25113165 TI - Does a child's fear of needles decrease through a learning event with needles? AB - BACKGROUND: Most children have a fear of needles. Suitable preparation can decrease the pain and fear of needles in hospitals; however, few have examined how such preparation affects healthy children. This study examined whether learning with needles decreases fear of needles and changes motivation to get vaccinations in school-age children and the possible association between fear of needles and motivation toward vaccinations. METHODS: This study included children participating in the "Let's Be Doctors" event, which was held in 4 child centers in Tsukuba city, Ibaraki, Japan. In this event, children learned about injections and how a vaccine works, and injected a vaccine (water) into skin (sponge) using a real syringe and imitation needle. Data were collected just before and after the event by anonymous self-assessment questionnaires that used a 4-point Likert scale to assess fear of needles, motivation to get vaccinations, recommendation of vaccinations, and fear toward doctors among the children. Answers were divided into two categories for statistical analysis. RESULTS: In total, 194 children participated in the event and 191 children answered the questionnaire (response rate 98.5%). We analyzed 180 subjects, comprising 79 boys (43.9%) and 94 girls (52.2%), mean age of 8.1 +/- 1.0 years. The number of children reporting a fear of needles decreased from 69 (38.3%) before the event to 51 (28.3%) after the event, and those unwilling to get vaccinations decreased from 48 (26.7%) to 27 (15.0%). Children who reported fear of needles before the event were more unwilling to get vaccinations than those with no fear of needles (36 [52.2%] vs. 12 [10.8%]), while after the event the number of needle-fearing children unwilling to get vaccinations decreased to 19 (27.5%). CONCLUSIONS: Children's fear of needles and unwillingness to get vaccinations were decreased after experiencing a learning event with needles. The fear of needles is associated with a negative motivation to get vaccinations in children. PMID- 25113164 TI - Pharmacological interventions for sleepiness and sleep disturbances caused by shift work. AB - BACKGROUND: Shift work results in sleep-wake disturbances, which cause sleepiness during night shifts and reduce sleep length and quality in daytime sleep after the night shift. In its serious form it is also called shift work sleep disorder. Various pharmacological products are used to ameliorate symptoms of sleepiness or poor sleep length and quality. OBJECTIVES: To evaluate the effects of pharmacological interventions to reduce sleepiness or to improve alertness at work and decrease sleep disturbances whilst off work, or both, in workers undertaking shift work in their present job and to assess their cost effectiveness. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, PubMed and PsycINFO up to 20 September 2013 and ClinicalTrials.gov up to July 2013. We also screened reference lists of included trials and relevant reviews. SELECTION CRITERIA: We included all eligible randomised controlled trials (RCTs), including cross-over RCTs, of pharmacological products among workers who were engaged in shift work (including night shifts) in their present jobs and who may or may not have had sleep problems. Primary outcomes were sleep length and sleep quality while off work, alertness and sleepiness, or fatigue at work. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We performed meta-analyses where appropriate. MAIN RESULTS: We included 15 randomised placebo-controlled trials with 718 participants. Nine trials evaluated the effect of melatonin and two the effect of hypnotics for improving sleep problems. One trial assessed the effect of modafinil, two of armodafinil and one examined caffeine plus naps to decrease sleepiness or to increase alertness.Melatonin (1 to 10 mg) after the night shift may increase sleep length during daytime sleep (mean difference (MD) 24 minutes, 95% confidence interval (CI) 9.8 to 38.9; seven trials, 263 participants, low quality evidence) and night-time sleep (MD 17 minutes, 95% CI 3.71 to 30.22; three trials, 234 participants, low quality evidence) compared to placebo. We did not find a dose-response effect. Melatonin may lead to similar sleep latency times as placebo (MD 0.37minutes, 95% CI - 1.55 to 2.29; five trials, 74 participants, low quality evidence).Hypnotic medication, zopiclone, did not result in significantly longer daytime sleep length compared to placebo in one low quality trial and we could not use the data from the study on lormetazepam.Armodafinil taken before the night shift probably reduces sleepiness by one point on the Karolinska Sleepiness Scale (KSS) (MD -0.99, 95% CI -1.32 to 0.67; range 1 to 10; two trials, 572 participants, moderate quality evidence) and increases alertness by 50 ms in a simple reaction time test (MD -50.0, 95% CI 85.5 to -15.5) at three months' follow-up in shift work sleep disorder patients. Modafinil probably has similar effects on sleepiness (KSS) (MD -0.90, 95% CI 1.45 to -0.35; one trial, 183 participants, moderate quality evidence) and alertness in the psychomotor vigilance test in the same patient group. Post marketing, severe skin reactions have been reported. Adverse effects reported by trial participants were headache, nausea and a rise in blood pressure. There were no trials in non-patient shift workers.Based on one trial, caffeine plus pre shift naps taken before the night shift decreased sleepiness (KSS) (MD -0.63, 95% CI -1.09 to -0.17).We judged most trials to have a low risk of bias even though the randomisation method and allocation concealment were often not described. AUTHORS' CONCLUSIONS: There is low quality evidence that melatonin improves sleep length after a night shift but not other sleep quality parameters. Both modafinil and armodafinil increase alertness and reduce sleepiness to some extent in employees who suffer from shift work sleep disorder but they are associated with adverse events. Caffeine plus naps reduces sleepiness during the night shift, but the quality of evidence is low. Based on one low quality trial, hypnotics did not improve sleep length and quality after a night shift.We need more and better quality trials on the beneficial and adverse effects and costs of all pharmacological agents that induce sleep or promote alertness in shift workers both with and without a diagnosis of shift work sleep disorder. We also need systematic reviews of their adverse effects. PMID- 25113166 TI - The effects of steroid hormone exposure on direct gene regulation. AB - Steroid hormones have been widely overlooked as controllers of gene expression. Through the mechanisms of gene expression (DNA methylation, histone methylation, and RNAi), we discuss the impact of normal reproductive templates on the pulsatility and amplitude of potential gene-regulating treatment protocols. By examining the interactions of estradiol (E2) and progesterone (P4) in women, we propose that changes in physiologic reproductive hormone templates of exposure and timing can affect fertility and even cancer through the silencing or amplification of gene products; such as P53 and Bcl-2 in women. We suggest that uncontrolled hormone levels, due to aging and/or the environment, may be restored to a normal youthful template of gene expression through the fluctuating exogenous application of E2 and P4 that mimic the normal hormonal milieu of reproductive health. Furthermore, we hypothesize that restoration of normal hormone levels may lead to a lower risk of the chronic illnesses of aging and a better quality of life in patients suffering those conditions. PMID- 25113167 TI - Activity-dependent alterations in the sensitivity to BDNF-TrkB signaling may promote excessive dendritic arborization and spinogenesis in fragile X syndrome in order to compensate for compromised postsynaptic activity. AB - Fragile X syndrome (FXS), the most common cause of inherited human mental retardation, results from the loss of function of fragile X mental retardation protein (FMRP). To date, most researchers have thought that FXS neural pathologies are primarily caused by extreme dendritic branching and spine formation. With this rationale, several researchers attempted to prune dendritic branches and reduce the number of spines in FXS animal models. We propose that increased dendritic arborization and spinogenesis in FXS are developed rather as secondary compensatory responses to counteract the compromised postsynaptic activity during uncontrollable metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD). When postsynaptic and electrical activities become dampened in FXS, dendritic trees can increase their sensitivity to brain-derived neurotrophic factor (BDNF) by using the molecular sensor called eukaryotic elongation factor 2 (eEF2) and taking advantage of the tight coupling of mGluR and BDNF-TrkB signaling pathways. Then, this activity-dependent elevation of the BDNF signaling can strategically alter dendritic morphologies to foster branching and develop spine structures in order to improve the postsynaptic response in FXS. Our model suggests a new therapeutic rationale for FXS: correcting the postsynaptic and electrical activity first, and then repairing structural abnormalities of dendrites. Then, it may be possible to successfully fix the dendritic morphologies without affecting the survival of neurons. Our theory may also be generalized to explain aberrant dendritic structures observed in other neurobehavioral diseases, such as tuberous sclerosis, Rett syndrome, schizophrenia, and channelopathies, which accompany high postsynaptic and electrical activity. PMID- 25113168 TI - Editorial. PMID- 25113169 TI - Evaluation of radiocaesium wash-off by soil erosion from various land uses using USLE plots. AB - Radiocaesium wash-off associated with soil erosion in different land use was monitored using USLE plots in Kawamata, Fukushima Prefecture, Japan after the Fukushima Dai-ichi Nuclear Power Plant accident. Parameters and factors relating to soil erosion and (137)Cs concentration in the eroded soil were evaluated based on the field monitoring and presented. The erosion of fine soil, which is defined as the fraction of soil overflowed along with discharged water from a sediment trap tank, constituted a large proportion of the discharged radiocaesium. This indicated that the quantitative monitoring of fine soil erosion is greatly important for the accurate evaluation of radiocaesium wash-off. An exponential relationship was found between vegetation cover and the amount of eroded soil. Moreover, the radiocaesium concentrations in the discharged soil were greatly affected by the land use. These results indicate that radiocaesium wash-off related to vegetation cover and land use is crucially important in modelling radiocaesium migration. PMID- 25113170 TI - Selection of controls in the study of human neurodegenerative diseases in old age. AB - Human post-mortem brain tissue, mostly provided by brain banks, is precious because most human neurodegenerative diseases are restricted in their complete forms to human beings. However, the agonal state, post-mortem delay between death and tissue processing, variable vulnerability of chromatin, RNAs, proteins and metabolites can compromise the usability of the tissue material. Such factors must be considered and assessed in every experimental approach. The use of controls for comparative purposes to analyze diseased cases is crucial as the basic conditions of controls must be the same as those encountered in problem cases. Age, gender, region, hemisphere, and clear characterisation of objective neuropathological changes (e.g., Alzheimer's disease stages of Braak and Braak) in matching controls and problem cases must be considered in every study, and data must be clearly specified when presenting materials and methods in publications. Additional care must be taken regarding atypical neurodegenerative alterations, concomitant pathologies, and systemic diseases, together with drug consumption and treatments. The absence of neurological and mental symptoms and signs, although a sine qua non condition, is not sufficient to match control and problem cases for research. PMID- 25113172 TI - Vacancy patterning and patterning vacancies: controlled self-assembly of fullerenes on metal surfaces. AB - A density functional theory study accounting for van der Waals interactions reveals the potential of metal surface vacancies as anchor points for the construction of user-defined 2D patterns of adsorbate molecules via a controlled self-assembly process. Vice versa, energetic criteria indicate the formation of regular adsorbate-induced vacancies after adsorbate self-assembly on clean surfaces. These processes are exemplified by adsorbing C60 fullerene on Al(111), Au(111), and Be(0001) surfaces with and without single, triple, and septuple atom pits. An analysis of vacancy-adatom formation energetics precedes the study of the adsorption processes. PMID- 25113173 TI - Bis[N,N'-diisopropylbenzamidinato(-)]silicon(II): Lewis acid/base reactions with triorganylboranes. AB - Reaction of the donor-stabilized silylene 1 (which is three-coordinate in the solid state and four-coordinate in solution) with BEt3 and BPh3 leads to the formation of the Lewis acid/base complexes 2 and 3, respectively, which are the first five-coordinate silicon compounds with an Si?B bond. These compounds were structurally characterized by crystal structure analyses and by multinuclear NMR spectroscopic studies in the solid state and in solution. Additionally, the bonding situation in 2 and 3 was analyzed by quantum chemical studies. PMID- 25113171 TI - Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice. AB - Sporadic Alzheimer's disease (AD) is a multifactorial metabolic brain disorder characterized by progressive neurodegeneration. Decreased brain energy and glucose metabolism occurs before the appearance of AD symptoms and worsens while the disease progresses. Deregulated brain insulin signaling has also been found in AD recently. To restore brain insulin sensitivity and glucose metabolism, pioglitazone and rosiglitazone, two insulin sensitizers commonly used for treating type 2 diabetes, have been studied and shown to have some beneficial effects in AD mouse models. However, the molecular mechanisms of the beneficial effects remain elusive. In the present study, we treated the 3xTg-AD mice, a widely used mouse model of AD, with pioglitazone and rosiglitazone for 4 months and studied the effects of the treatments on cognitive performance and AD-related brain alterations. We found that the chronic treatment improved spatial learning, enhanced AKT signaling, and attenuated tau hyperphosphorylation and neuroinflammation. These findings shed new light on the possible mechanisms by which these two insulin sensitizers might be useful for treating AD and support further clinical trials evaluating the efficacy of these drugs. PMID- 25113174 TI - Incidence of alcohol use disorders among Hispanic subgroups in the USA. AB - OBJECTIVE: Hispanics are the largest ethnic minority group in the USA and a fairly heterogeneous group. But this heterogeneity has usually been ignored by grouping them into a single category. The objective of this study is to challenge that practice by providing alcohol use disorders (AUD) incidence and risk estimates across Hispanic subgroups. METHODS: A subsample of Hispanics (n = 2371) and non-Hispanic whites (n = 7741) at risk for AUD who participated in the first and second wave of the National Epidemiological Survey on Alcohol and Related Conditions was analyzed. Weighted incidence for AUD was calculated across Hispanic subgroups. A weighted modified Poisson generalized linear model was used to estimate relative risks. RESULTS: Compared with non-Hispanic whites, Puerto Ricans have the highest AUD incidence (3.6%; 95% CI: 0.5, 6.7) followed by Mexican-Americans (2.5%; 95% CI: 1.5, 3.6), Other Hispanics (1.6%; 95% CI: 0.1, 3.1) and Cuban-Americans (0.6%; 95% CI: 0.1, 1.2). In contrast, weighted adjusted relative risk estimates for Mexican-Americans were (RR = 3.2; 95% CI: 1.7, 6.2) but for Puerto Ricans (RR = 2.2; 95% CI: 1.0, 5.0) it was somewhat attenuated but still significant (P = 0.049). No difference was found for Cuban-Americans or Other Hispanics. CONCLUSIONS: The annual incidence and risk for AUD varies greatly among Hispanic subgroups. Nonetheless, the practice of categorizing Hispanics as a homogenous ethnic group still continues. Our findings suggest that this practice is not only inappropriate, but also hinders a better understanding of AUD etiology, prevention, treatment and rehabilitation in the largest ethnic minority group in the USA. PMID- 25113175 TI - Assessing restrictiveness of national alcohol marketing policies. AB - AIMS: To develop an approach for monitoring national alcohol marketing policies globally, an area of the World Health Organization's (WHO) Global Alcohol Strategy. METHODS: Data on restrictiveness of alcohol marketing policies came from the 2002 and 2008 WHO Global Surveys on Alcohol and Health. We included four scales in a sensitivity analysis to determine optimal weights to score countries on their marketing policies and applied the selected scale to assess national marketing policy restrictiveness. RESULTS: Nearly, 36% of countries had no marketing restrictions. The overall restrictiveness levels were not significantly different between 2002 and 2008. The number of countries with strict marketing regulations did not differ across years. CONCLUSION: This method of monitoring alcohol marketing restrictiveness helps track progress towards implementing WHO'S Global Alcohol Strategy. Findings indicate a consistent lack of restrictive policies over time, making this a priority area for national and global action. PMID- 25113177 TI - Blood levels of polychlorinated biphenyls and their hydroxylated metabolites in Baikal seals (Pusa sibirica): emphasis on interspecies comparison, gender difference and association with blood thyroid hormone levels. AB - We have previously demonstrated that Baikal seals (Pusa sibirica) are still being exposed to polychlorinated biphenyls (PCBs), and the population is at risk. In the present study, we measured the residue levels of PCBs and their hydroxylated metabolites (OH-PCBs) in the blood of Baikal seals and assessed the impact of OH PCBs on the thyroid function. Blood concentrations of PCBs and OH-PCBs were in the range of 2.8-130 ng g(-1)wet wt. and 0.71-4.6 ng g(-1)wetwt., respectively. Concentrations of higher-chlorinated OH-PCBs (hexa- to octa-PCBs) were more than 70% to total OH-PCB concentrations, indicating Baikal seals are mostly risked by higher-chlorinated OH-PCBs. High levels of 4OH-CB146 and 4OH-CB187 and low levels of 4OH-CB107/4'OH-CB108 found in Baikal seals were different from those in other phocidae species, suggesting the unique drug-metabolizing enzyme activities and/or contamination sources in this species. Concentrations of some OH-PCBs in males were significantly higher than those in females. These results suggest that these isomers may be preferentially transferred from mother to pup via cord blood. However, concentrations of almost all the isomers were not significantly correlated with the levels of blood total T3 and T4, implying less impact of PCB related compounds on the thyroid hormone circulation. PMID- 25113176 TI - The relationships between alcohol source, autonomy in brand selection, and brand preference among youth in the USA. AB - AIMS: We aimed to describe the sources from which youth in the USA commonly obtain alcohol, their role in selecting the brands they drink and the relationship of these variables to their indicated alcohol brand preferences. METHODS: We recruited 1031 underage drinkers in the age range of 13-20 through an internet panel managed by Knowledge Networks. Respondents completed an online survey assessing their recent brand-specific alcohol use, the source of their most recently consumed alcohol and whether the respondent or another person selected the brand they drank. RESULTS: Alcohol sources were more often passive than transactional. Nearly equal proportions of youth reported that they did versus did not choose the brand of their most recent drink. Analysis revealed that the brand preferences of passive versus active source drinkers were highly similar, as were the brand preferences of respondent versus non-respondent choice drinkers. Stratification of respondents by age did not significantly change these results. CONCLUSION: Our findings suggest that youth are consuming a homogenous list of preferred brands regardless of the source of their most recently obtained alcohol or who selected the brand they drank. PMID- 25113178 TI - Partition of organochlorine concentrations among suspended solids, sediments and brown mussel Perna perna, in tropical bays. AB - For evaluating the brown mussel Perna perna as a sentinel organism regarding environmental concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), the present study reports original data on the relationship between the concentrations of these chemicals in bottom surface sediments, suspended solids (SS) and concentrations bioaccumulated by this bivalve. Three P. perna cultivation areas, located at three bays in southeastern Brazil were used in this study. The three estuaries are under different degrees of environmental impact. Variations in the OCP and PCB concentrations bioaccumulated by the bivalves tended to be similar to those observed in the sediment, but differed from those found in SS. This latter difference might suggest that the SS trapping apparatuses should have been left in place for approximately 60 days (not only 15 days). This longer period would allow the integration of the environmental variability of the OCP and PCB burden adsorbed to this compartment. Authors encourage future studies to evaluate P. perna exposure to OCPs and PCBs through the evaluation of sediment concentrations. PMID- 25113179 TI - Contamination profiles of perfluoroalkyl substances in five typical rivers of the Pearl River Delta region, South China. AB - A survey on contamination profiles of eighteen perfluoroalkyl substances (PFASs) was performed via high performance liquid chromatography-tandem mass spectrometry for surface water and sediments from five typical rivers of the Pearl River Delta region, South China in summer and winter in 2012. The total concentrations of the PFASs in the water phase of the five rivers ranged from 0.14 to 346.72 ng L(-1). The PFAS concentrations in the water phase were correlated positively to some selected water quality parameters such as chemical oxygen demand (COD) (0.7913) and conductivity (0.5642). The monitoring results for the water samples showed significant seasonal variations, while those for the sediment samples showed no obvious seasonal variations. Among the selected 18 PFASs, perfluorooctane sulfonic acid (PFOS) was the dominant PFAS compound both in water and sediment for two seasons with its maximum concentration of 320.5 ng L(-1) in water and 11.4 ng g(-1) dry weight (dw) in sediment, followed by perfluorooctanoic acid (PFOA) with its maximum concentration of 26.48 ng L(-1) in water and 0.99 ng g( 1) dw in sediment. PFOS and PFOA were found at relatively higher concentrations in the Shima River and Danshui River than in the other three rivers (Xizhijiang River, Dongjiang River and Shahe River). The principal component analysis for the PFASs concentrations in water and sediment separated the sampling sites into two groups: rural and agricultural area, and urban and industrial area, suggesting the PFASs in the riverine environment were mainly originated from industrial and urban activities in the region. PMID- 25113180 TI - Distribution of organochlorine pesticides in sediments from Yangtze River Estuary and the adjacent East China Sea: implication of transport, sources and trends. AB - Thirty-eight surface sediments and two sediment cores were collected from Yangtze River Estuary (YRE) and adjacent East China Sea (ECS) to study the distribution patterns, origins, potential transport and burden of organochlorine pesticides (OCPs) in the marginal sea. Residues of OCPs ranged from 0.190 to 5.17 ng g(-1) dry weight with a distinct "band type" pattern under the control of Yangtze River inputs and ECS circulation system. Differences in transmission media and redox conditions in situ respectively resulted in the divergent distributions of alpha/beta-HCH and DDD/DDE. The compositional pattern analysis implied that OCPs in the inner shelf of ECS were derived from both "weathered" and fresh sources, whereas those in the outer shelf of ECS had undergone high metabolism. Concurrent with the land-sea migration, vertical profiles of sediment cores showed increasing trends or rebound since the 1990s, characteristic of two evident "jumps" of DDE+DDD/DDT and DDT/DDE ratios. Moreover, the primary distribution pattern founded for HCHs and the considerable mass inventories calculated (6.20 metric tones for OCPs) together suggested that the contaminated sediments in the studied area to be a potential source of OCPs to the global ocean. PMID- 25113181 TI - PAHs in decaying Quercus ilex leaf litter: mutual effects on litter decomposition and PAH dynamics. AB - The investigation of the relationships between litter decomposition and polycyclic aromatic hydrocarbons (PAHs) is important to shed light not only on the effects of these pollutants on fundamental ecosystem processes, such as litter decomposition, but also on the degradation of these pollutants by soil microbial community. This allows to understand the effect of atmospheric PAH contamination on soil PAH content via litterfall. At this aim, we studied mass and PAH dynamics of Quercus ilex leaf litters collected from urban, industrial and remote sites, incubated in mesocosms under controlled conditions for 361d. The results highlighted a litter decomposition rate of leaves sampled in urban>industrial>remote sites; the faster decomposition of litter of the urban site is also related to the low C/N ratio of the leaves. The PAHs showed concentrations at the beginning of the incubation of 887, 650 and 143 ng g( 1)d.w., respectively in leaf litters from urban, industrial and remote sites. The PAHs in litter decreased along the time, with the same trend observed for mass litter, showing the highest decrease at 361 d for the urban leaf litter. Anyway, PAH dynamics in all the litters exhibited two phases of loss, separated by a PAH increase observed at 246 d and mainly linked to benzo[e]pyrene. PMID- 25113182 TI - Residues and chiral signatures of organochlorine pesticides in mollusks from the coastal regions of the Yangtze River Delta: source and health risk implication. AB - The residues and enantiomeric fractions of organochlorine pesticides (OCPs) were measured in 11 mollusk species collected from the coastal areas along the Yangtze River Delta to evaluate the status, potential sources, and health risks of pollution in these areas. The concentrations of DDTs, HCHs, and chlordanes ranged from 6.22 to 398.19, 0.66-7.11, and 0.14-4.08 ng g(-1) based on wet weight, respectively; DDTs and HCHs have the highest values, globally. The DDTs increased and the HCHs decreased compared to historical data. Both the box-and-whisker plots and the one-way ANOVA tests indicated that the OCP levels varied little between sampling locations and organism species. The compositions of the DDTs and HCHs suggested a cocktail input pattern of fresh and weathered technical products. The comparative EF values for the alpha-HCH between the sediments and mollusks, as well as the lack of any discernible difference in the relative proportions of HCH isomers among different species from the same sampling site implied that the HCH residues in the mollusks came directly from the surrounding environment. However, the biotransformation of DDTs in mollusks cannot be precluded. The assessments performed based on several available guidelines suggested that although no significant human health risks were associated with the dietary intake of OCPs, the concentrations of DDTs exceeded the maximum residual limits of China and many developed nations. Moreover, an increased lifetime cancer risk from dietary exposure to either DDTs or HCHs remains a possibility. Because non-racemic OCP residues are common in the mollusk samples, our results suggest a need to further explore the levels and toxicity of the chiral contaminants in mollusks and other foodstuff to develop the human risk assessment framework based on chiral signatures. PMID- 25113183 TI - Comparison of the sorption behaviors and mechanisms of perfluorosulfonates and perfluorocarboxylic acids on three kinds of clay minerals. AB - The sorption of four perfluoroalkyl acids (PFAAs) [perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA) and perfluorohexanoic acid (PFHxA)] on three typical minerals [montmorillonite (MM), kaolinite (KL) and hematite (HM)] was studied. The sorption of PFOS and PFHxS was much stronger than PFOA and PFHxA. The sorption of each PFAA on the minerals followed an order of HM>KL>MM, even though MM was positively while KL and HM were negatively charged, implying that the sorption is driven by some other interactions besides electrostatic attraction. The sorption decreased with an increase in pH and a decrease in ionic strength of the solution, and their impacts on PFOS were much stronger than other three PFAAs. Surface complexing and hydrogen-bonding could make great contributions to the sorption of PFOS on the minerals. The results are important for understanding the transport and fate of PFAAs in sediment and ground water. PMID- 25113184 TI - Study of penetration behavior of PCB-DNAPL in a sand layer by a column experiment. AB - To better understand the infiltration performances of high concentration PCB oils (KC-300 and KC-1000 polychlorinated biphenyl (PCB) mixtures), representative dense non-aqueous phase liquid (DNAPL), under both saturated and unsaturated conditions, we conducted experiments on a sand column filled with Toyoura Standard Sand. When PCB oil with the volume comparable to the total porosity in the column was supplied, the residual PCB concentrations under PCB-water conditions were 4.9*10(4)mgkg(-1) in KC-300 and 3.9*10(4)mgkg(-1) in KC-1000. Under PCB-air conditions, residual PCB concentrations were 6.0*10(4)mgkg(-1) and 2.4*10(5)mgkg(-1) in the upper and lower parts for KC-300 and 3.6*10(4)mgkg(-1) and 1.5*10(5)mgkg(-1) in those for KC-1000, respectively, while the rest of the PCBs were infiltrated. On the other hand, when a small amount of PCB oil with the volume far smaller than the total porosity in the column was supplied, the original PCBs were not transported via water permeation. However, lower chlorinated PCB congeners-e.g., di- or tri-chlorinated biphenyls-preferentially dissolved and were infiltrated from the bottom of the column. These propensities on PCB oil infiltration can be explained in conjunction with the degree of PCB saturation in the sand column. PMID- 25113185 TI - Distribution of persistent organic pollutants (POPs) in cultured mussels from the Croatian coast of the Adriatic Sea. AB - In this study we investigated the distribution of 7 organochlorine pesticides (OCPs) and 17 polychlorinated biphenyl (PCBs) congeners in the edible tissue of the blue mussels (Mytilusgalloprovincialis) collected at 15 shellfish breeding farms and 1 harvesting area along the Croatian Adriatic coast. All analyzed OCPs were found in all samples (0.011-1.47 ng g(-)(1) w.wt.). Concentrations of PCB congeners in positive samples ranged between 0.007 and 7.66 ng g(-)(1) w.wt. The most abundant compounds were gamma-HCH, PCB-138 and PCB-153. Overall levels of PCBs and OCPs were in the lower end of the concentration ranges reported in literature. Significant differences of all contaminants were recorded between seasons, with higher values in the warmer part of the year. Results of the evaluation of the risks to human health associated with consumption of the mussels containing organic contaminants suggest that the levels of these compounds in mussels do not pose any threat for consumers of cultivated mussels. PMID- 25113186 TI - Study on the impact of industrial flue gases on the PCDD/Fs congener profile in ambient air. AB - The aim of this study was to examine the impact of emissions from combustion processes from sinter, medical, waste and sewage waste incineration plants on the PCDD and PCDF congener profile in ambient air in Krakow (city in Poland). The subject matter of the study were air samples from the outskirts and the city center. It was found that in flue gases from industrial sources and in ambient air the share of PCDF congeners in relation to the total content of PCDD/Fs was higher than the share of PCDDs. However, in air samples collected in the city center, this relationship was reversed. The PCDD congener profiles in flue gases and in air samples are comparable. However, in the samples from the city centre, the share of OCDD is significantly higher and amounts to about 80%. The PCDF congener shares show higher spatial diversity, although in all the analyzed air samples, ODCF and 1,2,3,4,6,7,8 HpCDF dominated. Analyzing the share of congeners in regard to the sum of PCDDs/Fs a mutual resemblance of air from the suburbs, exhaust gases from the sinter ore and sewage sludge incinerator plant was observed. The study showed a similarity between the profile of congeners in air from the city centre and exhaust gases from the medical waste incinerator. PMID- 25113187 TI - Polychlorinated biphenyls removal from contaminated soils using a transportable indirect thermal dryer unit: implications for emissions. AB - An assessment in China of the application of a transportable indirect thermal dryer unit for the remediation of soils contaminated with polychlorinated biphenyls (PCBs) demonstrated that it is well suited to remove PCBs from soils. A remarkable reduction of total PCBs in soils from 163-770 MUg g(-1) to 0.08-0.15 MUg g(-1) was achieved. This represented removal efficiencies of greater than 99.9% and an approximate 100% removal of the toxic equivalent of the PCBs. Furthermore, the emissions to the atmosphere from the unit were in compliance with current PCBs regulations. In conclusion, remediation of PCBs-contaminated soils based on a transportable indirect thermal dryer unit appears to be a highly efficient and environmentally sound treatment technology that has huge implications for cleaning thousands of regionally dispersed sites of PCBs contamination in China. PMID- 25113188 TI - Characterization and fate of polychlorinated biphenyls, polychlorinated dibenzo-p dioxins and polychlorinated dibenzofurans in soils and sediments at the Portsmouth Gaseous Diffusion Plant, Ohio. AB - The U.S. Department of Energy Portsmouth Gaseous Diffusion Plant is in the early stages of decommissioning and decontamination. During operations, the site drew a large amount of electric power and had multiple large switchyards on site. These are a source of polychlorinated biphenyls (PCB) contamination to both on-site and off-site streams. Some soil remediation has been completed in the main switchyard. During 2011 and 2012, fifteen sites were sampled at the surface (<10 cm) and subsurface (20-30 cm) to characterize the extent of PCB contamination, to identify weathering and migration of PCB contamination and to explore potential polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) contamination due to transformer fires and explosions in the 1950s and 1960s. Stagnant sites tended to exhibit more migration of contamination to deeper sediments than sites with fast-moving waters, and the highest concentrations were found at the bottom of a settling pond. A signature set of five dioxin-like PCBs were consistently found across the site with higher concentrations in carbon rich surface sediments. PCB concentrations had a significant inverse correlation with clay content, suggesting that PCBs did not bind to clays at this site. Remediation has reduced PCB concentrations throughout the site compared to levels found in previous studies and long-term upkeep of sediment lagoons is necessary to retain PCB and dioxin-rich sediments. The flow regimen, organic carbon and clay content play a very important role in the fate of PCBs in the environment at the surface as well as downward migration. PMID- 25113189 TI - QSAR studies of bioconcentration factors of polychlorinated biphenyls (PCBs) using DFT, PCS and CoMFA. AB - The bioconcentration factors (BCFs) of 58 polychlorinated biphenyls (PCBs) were modeled by quantitative structure-activity relationship (QSAR) using density functional theory (DFT), the position of Cl substitution (PCS) and comparative molecular field analysis (CoMFA) methods. All the models were robust and predictive, and especially, the best CoMFA model was significant with a correlation coefficient (R(2)) of 0.926, a cross-validation correlation coefficient (Q(2)) of 0.821 and a root mean square error estimated (RMSE) of 0.235. The results indicate that the electrostatic descriptors play a more significant role in BCFs of PCBs. Additionally, a test set was used to compare the predictive ability of our models to others, and results show that our CoMFA model present the lowest RMSE. Thus, the models obtain in this work can be used to predict the BCFs of remaining 152 PCBs without available experimental values. PMID- 25113190 TI - Bioaccumulation and biomagnification of persistent organic pollutants in Indo Pacific humpback dolphins (Sousa chinensis) from the Pearl River Estuary, China. AB - Indo-Pacific humpback dolphins (Sousa chinensis) are apex predators in the Pearl River Estuary waters (PRE) of China. PCBs, DDTs and other organochlorine pesticides (OCPs) (e.g., HCHs, HCB, mirex and dieldrin) were analysed in blubber samples of 45 dolphins and 10 prey fishes of S. chinensis collected from 2004 to 2013 in the PRE region to investigate the bioaccumulation and potential biomagnification of persistent organic pollutants (POPs). DDTs were the most abundant residue in the dolphins, with an average of 6,2700 ng g(-1) wet weight (ww), followed by PCBs (average: 1,790 ng g(-1) ww) and other OCPs including ?HCHs, mirex, endrin, ?chlordanes, HCB, dieldrin, aldrin, heptachlor, and pentachlorobenzene. The concentrations of PCBs and DDTs in male dolphins significantly increased with age and length. In contrast, female dolphins did not show obvious bioaccumulation trends with age and body length, possibly due to the lactational and parturitional transfer of these compounds. Compared with the POP residues in the prey fishes, the concentrations of PCBs, DDTs, and HCHs in the dolphin blubber increased by factors of 99, 212, and 5, respectively, whereas the residue levels of the other OCPs increased 2-185 times, indicating a potentially significant biomagnification in the top predators. The potential biomagnification factors calculated for most POPs were significantly higher than those in the cetacean species from other regions. PMID- 25113191 TI - Chronic effects of PFOA and PFOS on sexual reproduction of freshwater rotifer Brachionus calyciflorus. AB - Rotifers play an important role in the dynamics of freshwater and coastal marine ecosystems, and are also important tools for assessing toxicity in aquatic environments. In this study, the effects of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on the population growth rate and resting egg production of rotifer Brachionus calyciflorus were investigated. Reproductive bioassays indicated that PFOS increased the rotifer population growth rate at the concentration ?2.0 mg L(-1), and inhibited it at higher concentrations. For PFOA, the inhibition of population growth rate was observed when the concentration was greater than 4.0 mg L(-1). Exposure to PFOS (0.25 mg L(-1)) or PFOA (2.0 mg L( 1)) increased the mictic ratios of unexposed rotifer offspring. Population variation and increased mictic ratios were likely the two major factors leading to decline of resting egg production. The resting eggs formed under exposure to PFOA/PFOS in the range of 0.125-2.0 mg L(-1) showed higher hatching percentages in the control medium than that without PFOA/PFOS exposure. When the resting eggs were formed in the control medium and incubated in media with different levels of PFOA/PFOS, higher hatching percentages were induced by PFOS but lower hatching percentages induced by PFOA. The effects on the hatching rate of resting eggs with PFOA/PFOS exposure during the hatching period were greater than those with exposure during resting egg formation period, and the effect of PFOS was greater than that of PFOA. Both PFOA and PFOS exhibited slight effect on the hatching pattern. PMID- 25113193 TI - Mechanisms of transformation of polychlorinated diphenyl ethers into polychlorinated dibenzo-p-dioxins and dibenzofurans. AB - This study presents a detailed mechanistic account of the formation of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) from polychlorinated diphenyl ethers (PCDEs). It applies the recently developed meta hybrid M06-2X functional and deploys the 2,2'-dichlorodiphenylether (2,2' DCDE) molecule as a representative model compound for all PCDEs congeners. We find that, exceedingly high activation enthalpies prevent the direct formation of PCDFs from PCDEs via unimolecular elimination of HCl or Cl2. Rather, loss of an ortho H/Cl atom initiates the transformation of PCDEs into PCDD/Fs. Subsequent formation of PCDFs takes place through ring-closure reactions with modest activation enthalpies, whereas the addition of a ground state oxygen molecule at an apparent ortho radical site of a PCDE congener commences a complex, yet very exothermic, mechanism leading to the formation of PCDDs. Splitting the ether linkage through H/Cl addition at the pivot carbon constitutes a major source for the formation of chlorophenoxy radicals and chlorobenzene molecules. Our kinetic and mechanistic analyses demonstrate that, the degree and pattern of chlorination of PCDEs display a negligible effect on the formation pathways of PCDD/Fs from PCDEs. PMID- 25113192 TI - Consumption of foods of animal origin as determinant of contamination by organochlorine pesticides and polychlorobiphenyls: results from a population based study in Spain. AB - The level of contamination with persistent organic pollutants (POPs) and dietary habits and food consumption was extensively studied in the population from the Canary Islands (Spain). Because foodstuffs of animal origin are well known to be prominent contributors to these contaminants, the current study aimed to assess the role of the dietary intake of animal products as a probability factor for increased serum POPs. The intake of animal products (dietary variables) as a determining factor for serum POP levels was investigated using multivariate statistical models. Our results showed that while poultry, rabbit, and cheese consumption increases the probability of having high levels of non-DDT-derivative pesticides, sausage, yogurt, lard, and bacon consumption decreases the probability of having high levels of these pesticides. In addition, poultry, rabbit, eggs, cream, and butter consumption increased the probability of having detectable levels of marker PCB, while dairy desserts decreased the probability of having detectable levels of these PCBs. On the contrary, sausage and meat consumption increased the probability of having detectable levels of dioxin-like PCBs (DL-PCBs). The current results confirm that dietary intake of foodstuffs of animal origin is a relevant risk factor for the accumulation of POPs (and therefore their serum levels). Our study indicates that the analysis of dietary patterns may be useful for identifying those individuals that will probably present a high body burden of POPs. Because POPs can exert deleterious effects on human health, the identification of populations at risk of being highly contaminated is mandatory in order to implement policies that minimize the exposure to these compounds. PMID- 25113195 TI - Long-term potential of in situ chemical reduction for treatment of polychlorinated biphenyls in soils. AB - Polychlorinated biphenyls (PCBs) are well-known for being hydrophobic and persistent in the environment. Although many treatment approaches have been demonstrated to result in degradation of PCBs in water or water/cosolvent systems, few examples exist where such approaches have been applied successfully for PCB degradation in soil-water systems. A possible explanation for the limited treatment of PCBs in soil-water systems is that reactants that are capable of degrading PCBs in the aqueous phase are unlikely to persist long enough to achieve meaningful treatment of slowly-desorbing PCBs associated with the soil phase. To investigate this explanation, laboratory studies were conducted to evaluate chemical reductants, including zero valent metals, palladium (Pd) catalyst, and emulsified zero valent iron (EZVI), for dechlorination of PCBs in the presence and absence of soil. In the absence of soil, Pd-catalyzed treatments (Pd with electrolytic ZVI or iron/aluminum alloy) achieved rapid destruction of a model PCB congener, 2-chlorobiphenyl, with half-lives ranging from 43 to 110 min. For treatment of soils containing Aroclor 1248 at an initial concentration of approximately 1,500 mg kg(-1), Pd-catalyzed treatments achieved no measurable enhancement over the background PCB depletion rate (i.e., that measured in the untreated control) of 5.3 mg kg(-1)week(-1). In the presence of soils, EZVI was the only approach evaluated that resulted in a clear enhancement in PCB dechlorination rates. EZVI achieved PCB concentration reductions of greater than 50% at an average rate of 19 mg kg(-1)week(-1). The results suggest that slow PCB desorption limits treatment effectiveness in soils. PMID- 25113194 TI - Occurrence and possible sources of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) along the Chao River, China. AB - To analyze the possible influence of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) on Miyun Reservoir, 14 soil samples and 1 water sample were collected along the Chao River, which is the main upstream source of the reservoir. A total of 24 kinds of OCPs and 12 kinds of dioxin-like PCBs were measured. Results showed that the ?OCPs concentration ranged from 0.8145 to 16.8524 ng g(-1), and the ?PCBs ranged from 0.0039 to 0.0365 ng g(-1). Dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB) were the three dominant kinds of OCPs in this region, and the majority component of the PCBs was PCB-118 in both water and soil samples. The OCP ratios suggest that new inputs of lindane exist. DDTs mainly come from old technical inputs. HCHs might come from a new application of lindane, which highlights the importance of prohibited pesticide control. OCP concentrations were higher in corn fields and orchards and lower in forest lands and grasslands, which indicated that OCPs were very much influenced by human activities. The proportion of PCB components in this study area suggested that they mainly came from atmospheric deposition. PMID- 25113196 TI - Polychlorinated dibenzo-p-dioxins and dibenzofurans in water and six fish species from Dongting Lake, China. AB - There have been few studies of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in environmental water because of the large volume of water required for PCDD/Fs analysis. Water quality directly affects aquatic organisms, and little is known about how PCDD/Fs are transported in aquatic environments. PCDD/Fs were analyzed in eight water samples from Dongting Lake, China, which was contaminated with PCDD/Fs because of sodium pentachlorophenate use between the 1960s and the 1980s. The total PCDD/F concentrations in the samples were 36-345 pg L(-1), and the mean was 191 pg L(-1). Octachlorodibenzo-p dioxin was the most abundant PCDD/F congener in every sample, contributing 67-95% of the total 2,3,7,8-chlorinated PCDD/F concentrations. The toxic equivalent (WHO TEQ) concentrations in the samples were 0.17-0.37 pg L(-1), and the mean was 0.28 pg L(-1), which is higher than the Canadian environmental quality guideline (0.038 pg L(-1) WHO-TEQ for freshwater) and the United States Environmental Protection Agency water quality criterion (0.014 pg L(-1) WHO-TEQ). PCDD/Fs were also determined in six fish species collected from Dongting Lake, to assess the concentrations, accumulation patterns, and potential for toxic effects. The total 2,3,7,8-chlorinated PCDD/F concentrations in the fish samples were 2.2-17.9 pg g( 1) (wet weight), and the dominant congeners were octachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,7,8-hexachlorodibenzo-p dioxin, and 2,3,4,7,8-pentachlorodibenzofuran. The PCDD/F WHO-TEQs were 0.10-0.92 ww (3.3-65.3l w) pg g(-1) in different species of fish. PCDD/F congener patterns in fish may be affected by food chain biomagnification and the lipid content of the species. PMID- 25113198 TI - Time trends and congener profiles of PCDD/Fs, PCBs, and PBDEs in Baltic herring off the coast of Finland during 1978-2009. AB - In Finland, consumption of Baltic fatty fish may lead to high exposure to persistent organic pollutants (POPs), which might have hazardous health effects. Monitoring of POPs in Baltic fish enables the health authorities to keep dietary advice on fish consumption up to date. In this study, which is a compilation of analytical data from earlier studies, time trends and congener profiles of polychlorinated dioxins and furans (PCDD/Fs) and biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) in Baltic herring are reported. Altogether 344 samples of Baltic herring from 1978-2009 were collected across the Finnish coast of the Baltic Sea. The chemical analysis was performed in an accredited testing laboratory with high resolution gas chromatography mass spectrometry. During the 31-year period, PCDD/F and PCB concentrations decreased on approximately 80%, from approximately 20 to 5 pg/g fw, expressed as WHO2005 TEQ. The PBDE concentrations experienced a 4-10 fold increase during late 1980s-early 1990s, and declined to 1978s levels of approximately 2 ng/g fw by 2009. The current concentrations of PCDD/Fs, PCBs and PBDEs in Baltic herring are relatively low, and mostly below EU maximum accepted levels, and are expected to continue decreasing. In the future, it may be possible to re-evaluate the consumption restrictions for this specific Baltic fatty fish. PMID- 25113197 TI - Releases of chlorobenzenes, chlorophenols and dioxins during fireworks. AB - In fireworks, organic additives with high chlorine content such as hexachlorobenzene (HCB) are used for the improvement of illumination effects. In the course of a monitoring campaign for the detection of HCB in fireworks, atmospheric concentrations of chlorobenzenes (CBs), chlorophenols (CPs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), were measured during the Swiss National holiday August 1, 2011 which is celebrated with fireworks nationwide. Samples were collected in the city of Zurich using high volume air samplers equipped with quartz fiber filters and poly-urethane foam plugs. With one sampling period of 3h, a peak HCB concentration of 297 pg m(-3) was detected. Maximum total concentrations of pentachlorophenol and PCDD/Fs were 218 pg m(-3) and 61 fg I-TEQ m(-3), respectively. These levels are in the order of ten times above background concentrations measured one week before and two weeks after the event. Atmospheric emissions of HCB and CPs were quantified using a multimedia mass balance model to interpret the field measurements resulting in total emissions of HCB and CPs during the event of 23 g and 25 g, respectively. Based on per capita amounts this corresponds to total annual emissions from fireworks of 1.5 kg for each of the two pollutants in Switzerland. Starting from an estimation of the total worldwide emissions of HCB, in Switzerland emissions from fireworks may represent about 2-14% of total HCB releases. PMID- 25113199 TI - PCDD/Fs, PCBs and PBDEs in zooplankton in the Baltic Sea - spatial and temporal shifts in the congener-specific concentrations. AB - In the marine food-webs, zooplankton is a key element in the transfer of persistent organic pollutants to higher trophic levels. We determined the congener-specific concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in offshore zooplankton (size from 0.2 to 20mm) collected in 2001, 2002 and 2010 in the northern and central Baltic Sea. Of the PCDD/Fs, the concentrations of 2378-TCDF were from 18 to 47 and of 23478 PeCDF from 7.9 to 29 pg g(-1)fat and showed little temporal differences. However, 1234678-HpCDF and OCDF were abundant in 2001-2002 especially in the eastern Gulf of Finland (average concentrations 50 and 89 pg g(-1)fat, respectively). In 2010 the concentrations of these two congeners were lower, 29 and 30 pg g(-1)fat, respectively, but still substantially higher than in the other surveyed areas. The principal components analysis (PCA) supported that area-specific patterns in pollution strongly contributed to the congener profiles particularly in surface sediment and in sediment trap material, but even in zooplankton. The concentrations of the PCBs were highest in the Gulf of Finland and in the Bothnian Bay. The concentrations of most PCBs were somewhat lower in 2010 than in 2001-2002. Of the dioxin-like PCBs, the concentrations of PCB-77 were highest (271-572 pg g(-1)fat) but PCB-126 (32-113 pg g(-1)fat) contributed from 85% to 91% of the total toxicity of PCBs due to its higher toxic potency. Of the PBDEs, the BDE47 and BDE99 were the most abundant (concentrations from 1.2 to 4.6 and from 0.4 to 3.3 ng g(-1) fat, respectively). The concentrations of most PBDEs were lower in 2010 than in 2001/2002 except in the eastern Gulf of Finland. PMID- 25113200 TI - Fish consumption as a source of human exposure to perfluorinated alkyl substances in Italy: analysis of two edible fish from Lake Maggiore. AB - Extensive screening analyses of perfluorooctane sulfonate and related perfluorinated compounds (PFCs) in biota samples from all over the world have identified PFCs as global pollutants and have shown their bioaccumulation into higher trophic levels in the food chain. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are environmental contaminants belonging to a chemical group known as perfluorinated compounds. PFOS and PFOA are very persistent in the environment and bioaccumulate in humans. They are potential reproductive and developmental toxicants and are considered to be emerging endocrine disrupters. The United States Environmental Protection Agency (USEPA) considers both compounds to be carcinogenic and the European Food Safety Authority (EFSA) recently pointed out that they are associated with adverse health effects. Diet is considered the main source of exposure to PFCs, which have been found more frequently in fish and other seafood, compared to other food groups. In fact, aquatic ecosystems represent the final reservoir for PFCs due to their great affinity for sedimentary and living organic matter. In these systems, measured levels of persistent organic pollutants (POPs) could increase along the trophic web, ultimately affecting humans that consume aquatic species. In this study, PFOS and PFOA was detected by LC-MS/MS in muscle samples of Coregonus lavaretus (European whitefish) and Perca fluviatilis (European perch) collected from Lake Maggiore, a large lake located on the south side of the Italian Alps. PFOA was not found in any of the investigated samples above the limit of quantitation of 0.50 ng g(-1) fresh weight (fw), whereas PFOS was detected in all 90 samples with concentrations of up to 46.0 ng g(-1)fw. Mean concentrations were 22.2 ng g(-1)fw in P. fluviatilis and 20.0 ng g(-1)fw in C.lavaretus. Comparison of our results with literature data on PFOS intake suggested that fish from Lake Maggiore may be a significant source of dietary PFOS exposure, even if the reported values were lower than the Total Daily Intake (TDI) proposed by EFSA. PMID- 25113201 TI - Estimating stepwise debromination pathways of polybrominated diphenyl ethers with an analogue Markov Chain Monte Carlo algorithm. AB - A stochastic process was developed to simulate the stepwise debromination pathways for polybrominated diphenyl ethers (PBDEs). The stochastic process uses an analogue Markov Chain Monte Carlo (AMCMC) algorithm to generate PBDE debromination profiles. The acceptance or rejection of the randomly drawn stepwise debromination reactions was determined by a maximum likelihood function. The experimental observations at certain time points were used as target profiles; therefore, the stochastic processes are capable of presenting the effects of reaction conditions on the selection of debromination pathways. The application of the model is illustrated by adopting the experimental results of decabromodiphenyl ether (BDE209) in hexane exposed to sunlight. Inferences that were not obvious from experimental data were suggested by model simulations. For example, BDE206 has much higher accumulation at the first 30 min of sunlight exposure. By contrast, model simulation suggests that, BDE206 and BDE207 had comparable yields from BDE209. The reason for the higher BDE206 level is that BDE207 has the highest depletion in producing octa products. Compared to a previous version of the stochastic model based on stochastic reaction sequences (SRS), the AMCMC approach was determined to be more efficient and robust. Due to the feature of only requiring experimental observations as input, the AMCMC model is expected to be applicable to a wide range of PBDE debromination processes, e.g. microbial, photolytic, or joint effects in natural environments. PMID- 25113202 TI - Identifying the provenance of Leach's storm petrels in the North Atlantic using polychlorinated biphenyl signatures derived from comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry. AB - PCB signatures can be used for source identification, exposure studies, age dating and bio-monitoring. This study uses comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC-ToFMS) to produce a PCB signature comprised of over 80 PCBs for individual Leach's storm petrels (Oceanodroma leucorhoa). The Leach's storm petrel is a relatively small, elusive, understudied pelagic bird, which only returns to remote islands under darkness during the breeding season. Samples were obtained from 25 Leach's storm petrels found dead in Canada and the UK following storm events in 2006 and 2009. Tissue samples were extracted and analysed by GCxGC-ToFMS and results showed that 83 PCB congeners were present in >60% of samples. An assessment of the PCB signature in four different tissue types showed that it did not vary greatly in samples obtained from the gut, heart, liver and stomach. Multivariate statistical analysis identified a distinctive PCB signature in birds from Canada and Europe which was used to identify the regional provenance and transatlantic movement of individual birds. The findings showcase the ability of GCxGC-ToFMS to provide the high quality congener specific analysis that is necessary for PCB fingerprinting, as well as highlighting the potential of PCB signatures for use in ecological studies of movement, foraging and behaviour. PMID- 25113203 TI - Historical trends of inorganic and organic fluorine in sediments of Lake Michigan. AB - Total fluorine (TF), extractable organic fluorine (EOF) and poly- and per fluorinated compounds (PFCs) were measured in eight dated cores of sediment taken along with 27 surface sediments from Lake Michigan in 2010. Based on rates of sedimentation, total concentrations of PFCs (?PFCs) reached a maximum in the later 1990s and early 2000s. This result is consistent with rapid changes in production and subsequent sedimentation. Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are still the predominant PFCs in the cores, but in surface sediments, concentrations of perfluorobutane sulfonate (PFBS) and perfluorobutanoic acid (PFBA) are now occurring at concentrations comparable to those of PFOS and PFOA. This observation is consistent with shifts in patterns of production and use in the US and Canada. Concentrations of TF in sediments were greater than those of EOF. This result is consistent with a larger proportion of un-extractable fluorinated material in both surface sediments and in cores. PMID- 25113204 TI - Polychlorinated biphenyls in respirable particulate matter from different industrial areas in northern China. AB - As two typical industrial bases of China's great metropolises, Lingfen and Datong are affected by the steel industry, chemical plants, coal-fired power plants, and several coking plants, and face pollution from polychlorinated biphenyls (PCBs). Therefore, this study was conducted to determine the PCB concentrations in PM2.5 and PM2.5-10 samples obtained in Lingfen and Datong. We collected 22 respirable particulate matter samples (11 of PM2.5 and 11 of PM2.5-10) from Lingfen and Datong, and measured a total of 144 PCB congeners. The total PCB concentrations were 5.92-38.7 pg m(-3) (median: 21.58 pg m(-3)) in PM2.5 and 1.83-40.8 pg m(-3) (median: 24.3 pg m(-3)) in PM2.5-10 in Linfen, and 4.33-18.5 pg m(-3) (median: 11.9 pg m(-3)) in PM2.5 and 13.0-47.4 pg m(-3) (median: 17.4 pg m(-3)) in PM2.5 10 in Datong. Of the PCB homologues, the dominant PCBs detected in the various media were all trichlorobiphenyls (tri-CBs). Moreover, the PCB distributions in PM2.5 and PM2.5-10 samples were quite different in the two cities. This may be caused by the differences of the industrial structures, and their relatively unintentional release of PCBs in these cities. Source analysis revealed that the major PCB contaminants in Linfen and Datong were tri-CBs and di-CBs, which were possibly associated with unintentional release of PCBs. Toxic equivalency concentrations based on ten dioxin-like PCBs ranged from 4.0*10(-5) to 2.3*10(-3) pgWHO-TEQ m(-3) in Linfen, and 4.5*10(-4) to 2.6*10(-4) pgWHO-TEQ m(-3) in Datong. The presence of PCB pollution is a potential threat to the residents of Datong and Linfen. PMID- 25113206 TI - Inhibition of the de novo synthesis of PCDD/Fs on model fly ash by sludge drying gases. AB - Sludge drying gases (SDG), evolving from drying and mild thermal decomposition (<300 degrees C) of raw sewage sludge contain NH3 and SO2 as well as other N- and S-compounds. All of these are potential PCDD/Fs suppressants. It is indeed observed that these SDG suppress 2,3,7,8-substitued PCDD/Fs formation on Model Fly Ash (MFA) with an efficiency up to 97.6% in wt. units and 96% in I-TEQ, respectively. This suppression is strong for (the bulk of) PCDD/Fs, adsorbed on the model fly ash; conversely, sludge drying gases enhance PCDD/Fs desorption from MFA. Moreover, TCDD/Fs are suppressed least, possibly following stepwise dechlorination of higher chlorinated PCDD/Fs. Characteristics, such as the type, origins and amount of sludge, its moisture-, nitrogen- and sulfur content and the nature of the thermal treatment applied are all expected to influence upon the suppression capabilities. In this study three types of dry sludge are tested and applied as suppressant in four different amounts or modes. The quality of the sludge drying gases is continuously monitored: the Gasmet results reveal that NH3 and SO2 are the most important components of SDG. The MFA reaction residue is scrutinized by Scanning Electron Microscope (SEM) and Energy Dispersive Spectrometer (EDS) analysis. A large number of particles attaching to the surface of model fly ash are observed by SEM. Moreover, EDS analysis reveals that part of the chlorine in MFA is carried away with the SDG and replaced by sulfur, so that eliminating chlorine may be part of the inhibition mechanism. However, further research is still needed to establish the optimum operating modes and to confirm the role of both inorganic and organic nitrogen and sulfur compounds in the suppression of PCDD/Fs formation on model fly ash. PMID- 25113205 TI - Adjusting serum concentrations of organochlorine compounds by lipids and symptoms: a causal framework for the association with K-ras mutations in pancreatic cancer. AB - In clinically aggressive diseases, patients experience pathophysiological changes that often alter concentrations of lipids and environmental lipophilic factors; such changes are related to disease signs and symptoms. The aim of the study was to compare the effects of correcting for total serum lipids (TSL) and other clinical factors on the odds of mutations in the K-ras oncogene by organochlorine compounds (OCs), in logistic models, in 103 patients with exocrine pancreatic cancer (EPC) using a causal directed acyclic graph (DAG) framework. Results and likelihood of bias were discussed in the light of possible causal scenarios. The odds of K-ras mutated EPC was associated with some TSL-corrected OCs, including p,p'-DDT (p-value: 0.008) and polychlorinated biphenyl 138 (p-trend: 0.024). When OCs were not corrected by TSL, the OR of a K-ras mutation was significant for p,p'-DDT (p-trend: 0.035). Additionally adjusting for cholestatic syndrome increased the ORs of TSL-corrected OCs. When models were adjusted by the interval from first symptom to blood extraction (ISE), the ORs increased for both TSL corrected and uncorrected OCs. Models with TSL-corrected OCs and adjusted for cholestatic syndrome or ISE yielded the highest ORs. We show that DAGs clarify the covariates necessary to minimize bias, and demonstrate scenarios under which adjustment for TSL-corrected OCs and failure to adjust for symptoms or ISE may induce bias. Models with TSL-uncorrected OCs may be biased too, and adjusting by symptoms or ISE may not control such biases. Our findings may have implications as well for studying environmental causes of other clinically aggressive diseases. PMID- 25113207 TI - Spatial and seasonal distribution of organochlorine pesticides in the sediments of the Yangtze Estuary. AB - The spatial and seasonal distribution of organochlorine pesticides (OCPs) in the sediments of the Yangtze Estuary was investigated. The total concentration of 19 OCPs (?OCPs), including alpha-HCH, beta-HCH, gamma-HCH, delta-HCH, o, p'-DDE, p, p'-DDE, o, p'-DDD, p, p'-DDD, o, p'-DDT, p, p'-DDT, heptachlor, aldrin, heptachlor epoxide (Isomer B, Isomer A), endosulfan I, dieldrin, endrin, endosulfan II and methoxychlor, in the surface sediments ranged from 0.4 to 82.1 ng g(-1) d.w. The mean values of the ?OCPs were 8.5 +/- 8.3 ng g(-1) d.w., 26.7 +/- 12.1 ng g(-1) d.w., 40.5 +/- 18.2 ng g(-1) d.w., and 13.0 +/- 11.2 ng g(-1) d.w. for August 2010, November 2010, February 2011 and May 2011, respectively. The highest concentration of OCPs was detected at the river-sea boundary because of the intense resuspension and redeposition of sediments in this area. The OCPs preferred to accumulate in the inner estuary, rather than in the offshore area in the dry season, whereas the opposite occurred in the flood season. This phenomenon was related to the seasonal changes of the Changjiang diluted water (CDW). OCPs in the offshore area were controlled by the ocean currents and the monsoon. There was a southward increase for the OCP deposition in the offshore area in the winter. This increase resulted from the influences of the southward Yellow Sea coastal current and the East China Sea coastal current, as well as the northwest wind in winter. The Three Gorges Dam had an impact on HCH composition by changing the sediment redistribution during the deposition process. PMID- 25113208 TI - Sources, gastrointestinal absorption and stereo-selective and tissue-specific accumulation of Dechlorane Plus (DP) in chicken. AB - Dechlorane Plus (DP) isomers, along with two dechlorinated metabolites were measured in environmental matrices, chyme and digestive tract contents and tissues of chicken from an e-waste recycling site located in South China. Soil is proved to be the main source of DP in chicken rather than food because soil contributes more than 94% of total DP in chyme. In the gastrointestinal tract absorption processes, no selective absorption was observed for DP isomers during the ingestion processes. The tissue distribution of DP isomers in chicken exhibits complicated characteristics. The lipid contents in tissues are the main factors in the tissue distribution of DP, while the different blood perfusion state and the different tissue functions also seem to influence the tissue distribution of DP. The fat, brain, and liver exhibit higher fanti values (0.65, 0.64, and 0.64) than the other tissues (0.54-0.59). The elevated fanti values of DP from the contamination source (0.52 in soil) to chicken suggest stereoselective bioaccumulation of anti-DP in chicken. The similar ratios of anti Cl11-DP to anti-DP between soil and chicken imply that anti-Cl11-DP mainly derives from the uptake from environment rather than in vivo dechlorination. PMID- 25113209 TI - Spatial distributions of methoxylated and hydroxylated polybrominated diphenyl ethers in the East China Sea--a seaward increasing trend. AB - Methoxylated (MeO-) and hydroxylated (OH-) polybrominated diphenyl ethers (PBDEs) in marine environments have been of increasing concern due to their potential ecological toxicities and worldwide occurrence. However, few reports have been referred to their occurrence and distributions in marine sediments despite large numbers of studies on marine organisms have been reported. In the present paper, nine MeO-BDEs, ten OH-BDEs and three phytoplankton biomarkers (PBs) of brassicasterol, dinosterol and alkenones have been measured in surface sediments from the East China Sea. 6-MeO-BDE47, 2'-MeO-BDE68 and 6-OH-BDE47 were predominant congeners, ranging from 5.2 to 599.5 pg g(-1)dw, 5.2 to 562.4 pg g( 1)dw, and 11.4 to 129.1 pg g(-1)dw, respectively. Their spatial patterns all presented a seaward increasing trend and higher levels of these compounds were mainly concentrated in the outer shelf influenced by the Kuroshio Current. The patterns further prove that these ortho-substituted MeO-BDEs and OH-BDEs in marine sediments are natural compounds. Furthermore, alkenones also presented a seaward increasing trend. Statistical analysis shows that there are significant correlations between MeO-BDEs, OH-BDEs and alkenones, impling the potential of coccolithophorids for producing these natural compounds and their global distribution, especially in open oceans. Comparison between TOC and the ratio of 6-MeO-BDE47/6-OH-BDE47 suggests that TOC should be a potential controlling factor of the conversion between MeO-BDE and OH-BDE pairs. PMID- 25113210 TI - Tea saponin enhanced biodegradation of decabromodiphenyl ether by Brevibacillus brevis. AB - Decabromodiphenyl ether (BDE209) is a ubiquitous persistent pollutant and has contaminated the environment worldwide. To accelerate BDE209 elimination and reveal the mechanism concerned, the biosurfactant tea saponin enhanced degradation of BDE209 by Brevibacillus brevis was conducted. The results revealed that tea saponin could efficiently increase the solubility of BDE209 in mineral salts medium and improve its biodegradation. The degradation efficiency of 0.5 mg L(-1) BDE209 by 1 g L(-1) biomass with surfactant was up to 55% within 5d. Contact time was a significant factor for BDE209 biodegradation. BDE209 biodegradation was coupled with bioaccumulation, ion release and utilization, and debromination to lower brominated PBDE metabolites. During the biodegradation process, B. brevis metabolically released Na(+), NH4(+), NO2(-) and Cl(-), and utilized the nutrient ions Mg(2+), PO4(3-) and SO4(2-). GC-MS analysis revealed that the structure of BDE209 changed under the action of strain and nonabromodiphenyl ethers (BDE-208, -207 and -206), octabromodiphenyl ethers (BDE 203, -197 and -196) and heptabromodiphenyl ether (BDE-183) were generated by debromination. PMID- 25113211 TI - Correlation between human maternal-fetal placental transfer and molecular weight of PCB and dioxin congeners/isomers. AB - Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure. PMID- 25113212 TI - Levels of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and dioxin like PCBs in free range eggs from Vietnam, including potential health risks. AB - Chicken and duck eggs collected from three different areas in Vietnam were examined for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). These regions included a background area, an area sprayed with Agent Orange and the Bien Hoa airbase area where Agent Orange was handled by the US Army. The latter area now is inhabited and people keep their own laying hens. Egg samples were first screened with an in vitro reporter gene bioassay and a selection was analyzed by GC/HRMS. Samples from Bien Hoa airbase showed very high PCDD/F levels, up to 249 pg dioxin-equivalents (TEQ)/g fat, mainly due to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). In the sprayed areas, levels (3.2-8.2 pg TEQ g(-1)) were comparable to those observed in background areas (3.2-8.2 pg TEQ g( 1) fat). The estimated average consumption of 22 g d(-1) of the highly contaminated eggs will result in a 2-fold exceedance of the current exposure limits for adults and 5-fold for children, even without considering other contaminated food sources. This indicates a potential health risk from consumption of these highly contaminated eggs, which were not yet considered as a source for exposure to PCDD/Fs of people living in the highly contaminated areas. PMID- 25113213 TI - Kinetic study of chlordecone orally given to laying hens (Gallus domesticus). AB - The former use of chlordecone (CLD) in the French West Indies has resulted in long-term pollution of soils. In this area, CLD may be transferred into eggs of hens reared outdoors, through soil ingestion. In order to assess this risk, a kinetic study involving the contamination of laying hens (22 weeks of age) with a diet containing 500 MUg CLD kg(-1) during 42 d, followed by a depuration period of 35 d was carried out. Forty-four hens were sequentially slaughtered all over the experimental period and their liver, egg, abdominal fat and serum were collected. Two additional edible tissues, pectoral and leg muscles, were collected in hens slaughtered at the end of the contamination period. The depuration half-life of CLD in liver, egg, abdominal fat and serum was estimated at 5.0 +/- 0.38 (mean +/- SE), 5.5 +/- 0.29, 5.3 +/- 0.37 and 5.1 +/- 0.66 d, respectively. CLD concentration at the end of the contamination period reached 1640 +/- 274, 460 +/- 41, 331 +/- 23, and 213 +/- 8.5 MUg kg(-1) fresh matter (FM), respectively. The corresponding concentrations in pectoral and leg muscles were 119 +/- 8.4, 127 +/- 11 MUg kg(-1) FM, respectively. The steady state carry over rate of CLD in eggs reached 43 +/- 7.6%. This experiment demonstrates the preferential accumulation of CLD in liver, its significant transfer to eggs and its quite short half-life. It is concluded that raising hens on even mildly contaminated areas would lead to products exceeding the regulatory maximum residue limit of 20 MUg CLD kg(-1). PMID- 25113214 TI - The occurrence of organic contaminants in European eel (Anguilla anguilla) in Poland: an environmental quality assessment. AB - The objective of the present study was to provide information on the levels of pollutants in the tissues of eels caught in Polish waters. The contaminants included in the study are those which have not yet been widely studied in eel stocks, but which arouse concern in relation to the environment. An overview of the pollutant levels in eels caught in other European waters was also conducted. The results are evaluated in terms of environmental quality and consumer health. The mean concentrations of SigmaPBDEs and SigmaHBCDs in muscles of eels sampled in Polish waters were between 1 and 2 ng g(-1) ww. The mean TBT concentrations were between 2 and 4 ng g(-1)ww with the exception of samples from the Szczecin Lagoon, in which the mean TBT concentration was about tenfold higher. PMID- 25113215 TI - Polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (DDE) concentrations in maternal and umbilical cord serum in a human cohort from South Portugal. AB - Organochlorine compounds as polychlorinated biphenyls (PCBs) and pp' dichlorodiphenyldichloroethylene (pp'DDE) are ubiquitous, resistant to degradation and lipophilic compounds, commonly found in the general population. Prenatal exposure to these compounds has been associated to adverse developmental effects. Levels of PCBs and pp'DDE were investigated in maternal and umbilical cord serum of 68 women/newborns pairs from Algarve, South Portugal. Mean sum PCBs congeners and pp'DDE concentrations were 1.62 +/- 0.39 ng mL(-1)and 1.11 +/- 0.69 ng mL(-1)-for maternal and 1.45 +/- 0.25 ng mL(-1) and 0.85 +/- 0.50 ng mL(-1)for cord serum, respectively. Congeners distribution pattern followed the order PCB 153>180>130, both for maternal and cord serum). Significant correlations (p<0.05) were found between maternal and cord serum concentrations. The umbilical cord/maternal serum ratio were 0.90 and 0.76, respectively for SigmaPCB and pp'DDE Multivariate analyses relate women in urban centers with higher PCB levels, while higher pp'DDE relates to older primiparous women that live at rural areas. PCBs were also correlated to more portions of fat rich foods, while pp'DDE is associated to higher ingestion of vegetables and fruits. Smoking habits only correlated to maternal PCB. The present work provides, to our knowledge and for the first time, baseline human-biomonitoring data and establishes background ranges of PCB and pp'DDE levels in the maternal and umbilical cord serum in the Algarve region. These compounds exhibited the capacity to pass the placenta barrier and target the fetus. Even in non-industrialized areas, and in non intensive agriculture areas, like the Southern Portugal, there is a need to take measures to eliminate or minimize the risk of organochlorine exposure during pregnancy. PMID- 25113216 TI - Influence of persistent organic pollutants on oxidative stress in population based samples. AB - Persistent organic pollutants (POPs) are a large group of chemicals widely used and produced in various industrial applications. Many cell culture/animal studies have shown that POPs can induce oxidative stress. Since such data is lacking in humans, we conducted a large population-based study to analyze associations between POPs and oxidative stress markers. We measured following POPs; 16 polychlorinated biphenyls (PCBs), 5 organochlorine (OC) pesticides, octachlorinated dibenzo-p-dioxin, and polybrominated diphenyl ether 47, and oxidative stress markers; homocysteine, reduced [GSH] and oxidized glutathione [GSSG], glutathione ratio [GSSG/GSH], total glutathione, oxidized low-density lipoprotein [ox-LDL], ox-LDL antibodies, conjugated dienes, baseline conjugated dienes of LDL, and total anti-oxidative capacity in plasma samples collected from 992 70-year old individuals (50% women) from the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Linear regression analyses were performed to study the associations between oxidative stress markers and summary measures of POPs including the total toxic equivalence (TEQ), sums of PCBs and OC pesticides (main exposures) while adjusting for potential confounders. In multivariable-adjusted analyses, sum of PCBs showed strong associations with ox-LDL (beta=0.94; P=2.9*10(-6)). Further, sum of PCBs showed association with glutathione-related markers (GSSG: beta=-0.01; P=6.0*10( 7); GSSG/GSH: beta=-0.002; P=9.7*10(-10)), although in reverse direction. Other summary measures did not show any significant association with these markers. In our study of elderly individuals from the general population, we show that plasma levels of POPs are associated with markers of increased oxidative stress thereby suggesting that even low dose background exposure to POPs may be involved in oxidative stress. PMID- 25113217 TI - Sorption behaviors of a persistent toxaphene congener on marine sediments under different physicochemical conditions. AB - Sorptive processes are important parameters affecting the mobility, availability and fate of persistent organic pollutants (POPs), such as toxaphene, in aquatic systems. The sorption and desorption behaviors of the B7-1450, a stable toxaphene congener in environment, on marine sediment was studied under different temperature and salinity conditions to better understand the B-1450 distribution in estuarine systems. The data were fitted to different sorption models to characterize sorption behaviors by evaluating sorption coefficients and sequestrated fraction of B7-1450 on sediments. High carbon-normalized sorption coefficients (Koc) of the B7-1450 were observed with values ranging from 3.2*104 to 6.0*104 mL g(-1) under experimental conditions. The data showed an increase of B7-1450 sorption coefficients with the salinity and a decrease with temperature. These investigations indicate that B7-1450 is three times more sequestred on sediments in cold (2 degrees C, 30 psu) than in warm marine conditions (20 degrees C, 30 psu). These results suggest that the mobility and bioavailable of B7-1450 or other POPs from the sediments could be less important in cold marine comparatively in warm marine and warm freshwater media. As a result of climate changes, the warming of mid and high latitudes coastal waters could enhance the mobility of POPs. PMID- 25113218 TI - Spatial and seasonal distributions of polychlorinated dibenzo-p-dioxins and dibenzofurans and polychlorinated biphenyls around a municipal solid waste incinerator, determined using polyurethane foam passive air samplers. AB - Twenty-six ambient air samples were collected around a municipal solid waste incinerator (MSWI) in the summer and winter using polyurethane foam passive air samplers, and analyzed to assess the spatial and seasonal distributions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs). Three stack gas samples were also collected and analyzed to determine PCDD/F (971 pg m(-3) in average) and PCB (2,671 pg m(-3) in average) emissions from the MSWI and to help identify the sources of the pollutants in the ambient air. The total PCDD/F concentrations in the ambient air samples were lower in the summer (472-1,223 fg m(-3)) than the winter (561-3913 fg m(-3)). In contrast, the atmospheric total PCB concentrations were higher in the summer (716 4,902 fg m(-3)) than the winter (489-2,298 fg m(-3)). Principal component analysis showed that, besides emissions from the MSWI, the domestic burning of coal and wood also contributed to the presence of PCDD/Fs and PCBs in the ambient air. The PCDD/F and PCB spatial distributions were analyzed using ordinary Kriging Interpolation and limited effect was found to be caused by emissions from the MSWI. Higher PCDD/F and PCB concentrations were observed downwind of the MSWI than in the other directions, but the highest concentrations were not to be found in the direction with the greatest wind frequency which might be caused by emissions from domestic coal and wood burning. We used a systemic method including sampling and data analysis method which can provide pioneering information for characterizing risks and assessing uncertainty of PCDD/Fs and PCBs in the ambient air around MSWIs in China. PMID- 25113220 TI - Gender differences in alcohol demand: a systematic review of the role of prices and taxes. Comment on conclusions by Nelson. PMID- 25113219 TI - Determination of organochlorines, polychlorinated biphenyls and polybrominated diphenyl ethers in human hair: estimation of external and internal exposure. AB - A novel method was developed for the analysis of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in human hair samples. External contaminants of hair were extracted with acetone under sonication, while washed hair was further hydrolyzed in formic acid and acetone (1:4, v/v) with microwave assisted extraction (MAE) for internal contaminant measurements. Both internal and external extracts were cleaned up with gel permeation chromatography (GPC) and then solid phase extraction (SPE), before analyzed by a large volume injection-gas chromatography-tandem mass spectrometry (LVI-GC-MS/MS) using triple quadruple mass analyzer. Good linearity (R(2)? 0.996) was established within a concentration range between 0.1 and 100 ng mL(-)(1) among all target analytes. The method was validated for accuracy, precision and sensitivity. The developed method is intended to be cost effective and robust for the routine human hair analysis of PCBs, PBDEs and OCPs including acid-labile OCPs. The described method has been applied in pilot biomonitoring study and the preliminary data suggested that the contaminant profiles with the use of partial least-squares analysis discriminant analysis (PLA-DA) could be useful in differentiating external and internal exposure. PMID- 25113221 TI - The reaction enthalpy of hydrogen dissociation calculated with the Small System Method from simulation of molecular fluctuations. AB - We show how we can find the enthalpy of a chemical reaction under non-ideal conditions using the Small System Method to sample molecular dynamics simulation data for fluctuating variables. This method, created with Hill's thermodynamic analysis, is used to find properties in the thermodynamic limit, such as thermodynamic correction factors, partial enthalpies, volumes, heat capacities and compressibility. The values in the thermodynamic limit at (T,V, MUj) are then easily transformed into other ensembles, (T,V,Nj) and (T,P,Nj), where the last ensemble gives the partial molar properties which are of interest to chemists. The dissociation of hydrogen from molecules to atoms was used as a convenient model system. Molecular dynamics simulations were performed with three densities; rho = 0.0052 g cm(-3) (gas), rho = 0.0191 g cm(-3) (compressed gas) and rho = 0.0695 g cm(-3) (liquid), and temperatures in the range; T = 3640-20,800 K. The enthalpy of reaction was observed to follow a quadratic trend as a function of temperature for all densities. The enthalpy of reaction was observed to only have a small pressure dependence. With a reference point close to an ideal state (T = 3640 K and rho = 0.0052 g cm(-3)), we were able to calculate the thermodynamic equilibrium constant, and thus the deviation from ideal conditions for the lowest density. We found the thermodynamic equilibrium constant to increase with increasing temperature, and to have a negligible pressure dependence. Taking the enthalpy variation into account in the calculation of the thermodynamic equilibrium constant, we found the ratio of activity coefficients to be in the order of 0.7-1.0 for the lowest density, indicating repulsive forces between H and H2. This study shows that the compressed gas- and liquid density values at higher temperatures are far from those calculated under ideal conditions. It is important to have a method that can give access to partial molar properties, independent of the ideality of the reacting mixture. Our results show how this can be achieved with the use of the Small System Method. PMID- 25113222 TI - Systematic review of diplommatinid land snails (Caenogastropoda, Diplommatinidae) endemic to the Palau Islands. (1) Generic classification and revision of Hungerfordia species with highly developed axial ribs. AB - Diplommatinidae is a family of terrestrial caenogastropod snails that shows extensive species diversity and endemic radiation within the Palau (Belau) Islands. In this paper, we revised the taxonomy of Palauan endemic diplommatinids based on the comparative morphology of shell, operculum, radula, and genitalia. Although the generic classification of Palauan diplommatinids has been confusing, they are currently classified into two genera, Hungerfordia Beddome, 1889 and Palaina Semper, 1865. Palauan diplommatinids of these two genera are primarily distinguished by the radular, genital and operculum morphology. However, shell morphology, on which taxonomy has traditionally been based, does not provide definitive characters for generic identification, because shell shape and sculpture are highly variable within each genus. Although Hungerfordia has long been known as a monotypic genus, the current study redefines the endemic genus to include a wider range of species that were formerly placed in Diplommatina or Palaina. Following species are transferred to Hungerfordia: H. alata (Crosse, 1866) comb. nov.; H. lamellata (Crosse, 1866) comb. nov.; H. pyramis (Crosse, 1866) comb. nov.; H. ringens (Crosse, 1866) comb. nov.; H. polymorpha (Crosse, 1866) comb. nov.; H. inflatula (Crosse, 1866) comb. nov.; H. lutea (Beddome, 1889) comb. nov.; H. aurea (Beddome, 1889) comb. nov.; H. gibboni (Beddome, 1889) comb. nov.; H. crassilabris (Beddome, 1889) comb. nov. Pseudopalaina Moellendorff in Kobelt & Moellendorff, 1898 (synonym nov.) is demoted as a junior synonym of Hungerfordia. Palaina is also redefined based on the internal shell features and operculum morphology, in addition to the external shell characters. Furthermore, Eupalaina Kobelt & Moellendorff, 1898 is restored as a subgenus of Palaina for Palauan species on the basis of a genital character. The taxonomy of Hungerfordia species with highly developed axial ribs is revised. H. pelewensis Beddome, 1889, H. lamellata (Crosse, 1866) comb. nov., and H. alata (Crosse, 1866) comb. nov. are redescribed with new morphological data. Following new taxa are described: H. triplochilus sp. nov., H. expansilabris sp. nov., H. nudicollum sp. nov., H. echinata echinata sp. et subsp. nov., H. echinata tubulispina subsp. nov., H. elegantissima sp. nov., H. goniobasis goniobasis sp. et subsp. nov., H. goniobasis dmasechensis subsp. nov., H. subalata sp. nov., H. pteropurpuroides sp. nov., H. papilio papilio sp. et subsp. nov., H. papilio stenoptera subsp. nov.. PMID- 25113223 TI - Twelve new Demospongiae (Porifera) from Chilean fjords, with remarks upon sponge derived biogeographic compartments in the SE Pacific. AB - This article reports on 12 new species originating from the Chilean fjords region, namely Clathria (Microciona) mytilifila sp. nov., Haliclona (Reniera) caduca sp. nov., Latrunculia (L.) ciruela sp. nov., Latrunculia (L.) copihuensis sp. nov., Latrunculia (L.) verenae sp. nov., Latrunculia (L.) yepayek sp. nov., Myxilla (Burtonanchora) araucana sp. nov., Neopodospongia tupecomareni sp. nov., Oceanapia guaiteca sp. nov., Oceanapia spinisphaera sp. nov., Suberites cranium sp. nov. and Tethya melinka sp. nov. The material studied was collected between 5 and 30 m depth at latitudes comprised between 42o and 50oS, and is part of a large collection of Chilean sponges gathered by an international team in a series of expeditions. Identification keys are provided for SE Pacific Suberites and Latrunculia, and the known species of Myxilla (Burtonanchora) and Neopodospongia. A trans-Pacific link to the New Zealand fauna was retrieved for the latter genus. Distribution ranges apparent from the materials studied here are judged too preliminary to allow any inference on biotic boundaries in the SE Pacific. A revision of earlier assertions about these biogeographic units and their boundaries concluded that very little support remains other than for existence of a Magellanic fauna. This is in part a consequence of revising the taxonomy of sponge species originally deemed to underpin these areas. Specifically, the former proposal of a Central to Southern Chile biogeographic unit (33-56oS) has been markedly undone. PMID- 25113224 TI - [Delayed anaphylaxis after ingestion of meat. Carbohydrate epitope galactose alpha-1,3-galactose as cause of severe anaphylactic reactions]. AB - The correlation between anaphylaxis after consumption of meat and the carbohydrate epitope galactose-alpha-1,3-galactose (alpha-Gal) was first described in oncologic patients treated with cetuximab. An association with tick bites and parasitosis is suspected. We report on a healthy patient who developed sudden anaphylactic reactions after the ingestion of meat. Serologic and skin tests confirmed sensitization to alpha-Gal. Avoiding the consumption of mammalian meat led to a complete absence of symptoms. PMID- 25113225 TI - Solvent induced rapid modulation of micro/nano structures of metal carboxylates coordination polymers: mechanism and morphology dependent magnetism. AB - Rational modulation of morphology is very important for functional coordination polymers (CPs) micro/nanostructures, and new strategies are still desired to achieve this challenging target. Herein, organic solvents have been established as the capping agents for rapid modulating the growth of metal-carboxylates CPs in organic solvent/water mixtures at ambient conditions. Co-3,5 pyridinedicarboxylate (pydc) CPs was studied here as the example. During the reaction, the organic solvents exhibited three types of modulation effect: anisotropic growth, anisotropic growth/formation of new crystalline phase and the formation of new crystalline phase solely, which was due to the variation of their binding ability with metal cations. The following study revealed that the binding ability was critically affected by their functional groups and molecular size. Moreover, their modulation effect could be finely tuned by changing volume ratios of solvent mixtures. Furthermore, they could be applied for modulating other metal-carboxylates CPs: Co-1,3,5-benzenetricarboxylic (BTC), Zn-pydc and Eu pydc etc. Additionally, the as-prepared Co-pydc CPs showed a fascinating morphology-dependent antiferromagnetic behavior. PMID- 25113226 TI - Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center. AB - Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch-Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death ('primary refractoriness'). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML. PMID- 25113228 TI - Olive mill wastewater treatment using a simple zeolite-based low-cost method. AB - Olive mill wastewater (OMW), a liquid by-product of the olive oil industry, represents a severe environmental problem owing to its high pollution load. In this study, successive columns containing different types of natural materials were investigated for their OMW treatment efficiency. Passing OMW through three columns of gravel, fine sand, and a mixture of acidified cotton and zeolite (weight:weight ratio of cotton:clinoptilolite of 2:1), followed by treatment with activated charcoal (AC) and lime, was the best treatment in terms of the quality of water obtained. This treatment decreased concentrations of [Formula: see text] , B, K, P, and total fat in OMW by mean percentages of 78.0, 92.4, 66.6, 48.3, and 93.3%, respectively. Furthermore, it decreased OMW turbidity and electric conductivity (EC) by 96.8 and 48.4%, respectively. Most contaminants were removed from the OMW in the cotton/clinoptilolite column owing to the high sorption affinity of clinoptilolite on its active sites. The AC was efficient for organic particle removal; meanwhile, lime was used to raise the pH of the treated OMW (TOMW) from 2.9 to 5.1. This simple method enables us to obtain environmentally friendly TOMW that can be safely used for irrigation. PMID- 25113227 TI - The ill surgeon: a review of common work-related health problems amongst UK surgeons. AB - INTRODUCTION: Health-care workers are subjected to various occupational hazards within the National Health Service (NHS). Surgeons are not excluded from this group due to the nature of work carried out on a daily basis. As a result, we set out to investigate the common work-related health issues a surgeon practising in the UK may encounter. METHOD: A literature search conducted on PubMed, EMBASE, MEDLINE(r) and Health Management Information Consortium (HMIC) revealed 66 literature papers between the years 1990 and 2013. Thirty-seven were excluded from our review process for various reasons. RESULTS: Surgeons in the UK are likely to be susceptible to stress, sharp injuries, burnout and psychiatric morbidities, substance abuse and musculoskeletal pain. Noise-induced hearing loss has been reported amongst orthopaedic surgeons due to the use of electric and air powered drills and saws. No reports of skin-related illness, respiratory illness, nosocomial infections or malignancies were found within the published UK literature of our targeted group although they have been noted in other specialties. CONCLUSION: These occupational hazards pose a huge risk to the NHS and the personal well-being of its surgeons. As such, the importance of early awareness and education alongside prompt intervention is duly emphasized. PMID- 25113229 TI - Revisiting the relationship between environmental and financial performance in Chinese industry. AB - The debate on the relationship between corporate or industrial environmental performance (EP) and financial performance (FP) has yet to be resolved, and studies need to examine the possible moderating effects on the EP-FP link. We argue that industrial EP has a positive effect on FP and that industrial munificence and resource slack can moderate the EP-FP link. Using a dataset from Chinese industrial firms, we examine the direct effect of industrial EP on FP and the indirect effects of industrial munificence and resource slack on the EP-FP link. Our results show that improving corporate or industrial-level EP significantly influences FP and that slack resources play a significant role on the EP-FP link. However, we found no significant moderating effect of industrial munificence on the link. PMID- 25113230 TI - The relationship between corporate environmental performance and environmental disclosure: an empirical study in China. AB - Based on a content analysis of 533 Chinese listed companies, this study examines how corporate environmental performance affects not only the level of detail of a company's environmental disclosures, but also what information is disclosed. The results show that (1) both poor and good performers have more disclosure than the median (i.e., "mixed") performers, which provides empirical evidence to support a nonlinear relationship between corporate environmental performance and environmental disclosure; (2) poor performers disclose more soft information on environmental performance than good performers, and good performers disclose more solid information; and (3) although poor performers increase disclosure after being exposed as environmental violators, they avoid disclosing negative environmental information, such as the violation and the associated penalties. This study provides additional evidence for a nonlinear relationship between environmental performance and disclosure in emerging markets, and suggests environmental disclosure may not be a valid signal to differentiate good performers from poor performers in contemporary China. PMID- 25113232 TI - Fast and accurate pressure-drop prediction in straightened atherosclerotic coronary arteries. AB - Atherosclerotic disease progression in coronary arteries is influenced by wall shear stress. To compute patient-specific wall shear stress, computational fluid dynamics (CFD) is required. In this study we propose a method for computing the pressure-drop in regions proximal and distal to a plaque, which can serve as a boundary condition in CFD. As a first step towards exploring the proposed method we investigated ten straightened coronary arteries. First, the flow fields were calculated with CFD and velocity profiles were fitted on the results. Second, the Navier-Stokes equation was simplified and solved with the found velocity profiles to obtain a pressure-drop estimate (Deltap (1)). Next, Deltap (1) was compared to the pressure-drop from CFD (Deltap CFD) as a validation step. Finally, the velocity profiles, and thus the pressure-drop were predicted based on geometry and flow, resulting in Deltap geom. We found that Deltap (1) adequately estimated Deltap CFD with velocity profiles that have one free parameter beta. This beta was successfully related to geometry and flow, resulting in an excellent agreement between Deltap CFD and Deltap geom: 3.9 +/- 4.9% difference at Re = 150. We showed that this method can quickly and accurately predict pressure-drop on the basis of geometry and flow in straightened coronary arteries that are mildly diseased. PMID- 25113231 TI - A low computational cost algorithm for REM sleep detection using single channel EEG. AB - The push towards low-power and wearable sleep systems requires using minimum number of recording channels to enhance battery life, keep processing load small and be more comfortable for the user. Since most sleep stages can be identified using EEG traces, enormous power savings could be achieved by using a single channel of EEG. However, detection of REM sleep from one channel EEG is challenging due to its electroencephalographic similarities with N1 and Wake stages. In this paper we investigate a novel feature in sleep EEG that demonstrates high discriminatory ability for detecting REM phases. We then use this feature, that is based on spectral edge frequency (SEF) in the 8-16 Hz frequency band, together with the absolute power and the relative power of the signal, to develop a simple REM detection algorithm. We evaluate the performance of this proposed algorithm with overnight single channel EEG recordings of 5 training and 15 independent test subjects. Our algorithm achieved sensitivity of 83%, specificity of 89% and selectivity of 61% on a test database consisting of 2221 REM epochs. It also achieved sensitivity and selectivity of 81 and 75% on PhysioNet Sleep-EDF database consisting of 8 subjects. These results demonstrate that SEF can be a useful feature for automatic detection of REM stages of sleep from a single channel EEG. PMID- 25113233 TI - 'More than skin-deep': biological essentialism in response to a distinctiveness threat in a stigmatized fan community. AB - We investigated how group distinctiveness threats affect essentialist beliefs about group membership in a stigmatized fan community. An experiment conducted on 817 members of the fan community revealed that highly identified fans who perceived significant stigmatization were the most likely to endorse essentialist beliefs about group membership when exposed to a distinctiveness threat via comparison to a highly similar (vs. dissimilar) outgroup. These results bridge essentialism research and research on distinctiveness threat by demonstrating the mutability of group essentialism beliefs as a defensive response to distinctiveness threats. Implications for future research are discussed. PMID- 25113235 TI - An integrative review of promoting trust in the patient-primary care provider relationship. AB - AIM: An integrative review of empirical studies on factors promoting trust in the patient-primary care provider relationship. BACKGROUND: Trust is essential to the patient-provider relationship. Patients with high trust in their healthcare providers have been found to have improved outcomes, including improved chronic disease management, increased use of preventative services and satisfaction with care. Breaches of trust in the healthcare system threaten trust. Exploring factors that promote trust in the patient-provider relationship is warranted. DESIGN: Integrative literature review. DATA SOURCES: Electronic databases searched included CINAHL, MEDLINE and PsycARTICLES, using combinations of the key term 'trust' with: concept, practitioner, provider, physician, developing, creating, engendering, promoting and establishing. The results were limited to original publications in English, published between 1998-2013. REVIEW METHODS: A review of the literature was conducted by two independent reviewers based on the criteria established by Cooper; Whittemore and Knafl; and Polit and Beck. Methodological assessment tools were used to organize, evaluate the quality of and synthesize the data. RESULTS: A new conceptual definition of promoting trust is proposed that includes three core qualities: interpersonal and technical competence, moral comportment and vigilance. Gaps in the literature still exist related to rural, young adult, older adult and well patient populations. CONCLUSION: The core qualities could serve as target areas for the development of interventions aimed at modifying provider behaviours so that trust can be established, maintained or improved. Future prospective longitudinal research studies are needed that enhance understanding of trust with multiple primary care provider types. PMID- 25113234 TI - Determinants of overweight and obesity among Bangladeshi diabetic women of reproductive age. AB - BACKGROUND: Several reproductive disorders with overweight and obesity are now known to be associated with insulin resistance. The study was aimed to assess the proportion and determinants of overweight and obesity among diabetic women of reproductive age. METHODS: This cross-sectional analytic study was conducted among 888 diabetic women of reproductive age attending the out-patient department (OPD) of the central hospital of the Diabetic Association. Body Mass Index (BMI) was used to assess the general obesity. Waist Circumference (WC), Waist-Hip Ratio (WHR) and Waist-Height Ratio (WHtR) were used to assess central obesity. RESULTS: The overall prevalence of overweight was 22% (95% CI 19-24) and that of obesity was 48% (95% CI 45-51). Prevalence of central obesity by waist circumference was 77%, by waist-hip ratio was 99.9% and by waist-height ratio was 89%. Overweight and obesity were higher in the age group of 45-49 years (49%) and 35-44 years (24%) respectively. On Pearson's correlation analysis, BMI and WC were significantly correlated with age (r = 0.135, p = 0.001; r = 0.162, p = 0.001) and income (r = 0.151, p = 0.001; r = 0.087, p = 0.009) respectively. WHR was also correlated with income (r = 0.094, p = 0.005). Moreover, WHtR was significantly correlated with age (r = 0.139, p = 0.001), income (r = 0.069, p = 0.04) and duration of diabetes (r = 0.073, p = 0.03).On binary logistic regression analysis, BMI was significantly associated with age, income and management of diabetes by Oral Hypoglycemic Agent (OHA) (p < 0.05). WC was significantly associated with age, income and management of diabetes by OHA and insulin (p < 0.05). Where, WHR was significantly associated only with duration of diabetes (p < 0.05). WHtR was significantly associated with age (p < 0.05), management of diabetes by OHA (p < 0.05) and insulin (p < 0.05) in this analysis. CONCLUSIONS: A high prevalence of both overweight and obesity exists in diabetic women of reproductive age in Bangladesh and it seems to be associated with increasing age, income, duration of diabetes, and use of oral hypoglycemic agents. PMID- 25113236 TI - Migration protocol to estimate metal exposure from mouthing copper and tin alloy objects. AB - BACKGROUND: Low blood lead levels previously thought to pose no health risks may have an adverse impact on the cognitive development of children. This concern has given rise to new regulatory restrictions upon lead metal containing products intended for child use. However few reliable experimental testing methods to estimate exposure levels from these materials are available. METHODS: The present work describes a migration test using a mimetic saliva fluid to estimate the chronic exposure of children to metals such as lead while mouthing metallic objects. The surrogate saliva medium was composed of: 150 mM NaCl, 0.16% porcine Mucin and 5 mM buffer MOPS, adjusted to pH 7.2. Alloys samples, in the form of polished metallic disc of known surface area, were subjected to an eight hours test. RESULTS: Two whitemetal alloys Sn/Pb/Sb/Cu and three brass alloys Cu/Zn/Pb were tested using the saliva migration protocol. In the case of the whitemetal alloys, first order release kinetics resulting in the release of 0.03 and 0.51 MUg lead/cm2 after 8 hours of tests were observed, for lead contents of 0.05 0.07% and 5.5%, respectively. Brasses exhibited linear incremental release rates of 0.043, 0.175 and 0.243 MUg lead/cm2h for lead contents of 0.1-0.2%, 1.7-2.2% and 3.1-3.5%, respectively. The linear regression analysis of lead release rates relative to Pb content in brasses yielded a slope of 0.08 MUg lead/cm2h%Pb (r2 = 0.92). Lead release rates were used to estimate the mean daily mouthing exposure of a child to lead, according to age-specific estimates of mouthing time behavior. Calculated daily intakes were used as oral inputs for the IEUBK toxicokinetic model, predicting only marginal changes in blood lead levels (0.2 MUg lead/dL or less) for children aged 0.5 to 1 years old exposed to either class of alloy. CONCLUSIONS: The results of this study as a whole support the use of migration data of metal ions, rather than total metal content, to estimate health risk from exposure to metals and metal alloys substances in children. PMID- 25113237 TI - Combination of classical test theory (CTT) and item response theory (IRT) analysis to study the psychometric properties of the French version of the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF). AB - OBJECTIVE: The study aimed to examine the construct validity and reliability of the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q SF) according to both classical test and item response theories. METHOD: The psychometric properties of the French version of this instrument were investigated in a cross-sectional, multicenter study. A total of 124 outpatients with a substance dependence diagnosis participated in the study. Psychometric evaluation included descriptive analysis, internal consistency, test-retest reliability, and validity. The dimensionality of the instrument was explored using a combination of the classical test, confirmatory factor analysis (CFA), and an item response theory analysis, the Person Separation Index (PSI), in a complementary manner. RESULTS: The results of the Q-LES-Q-SF revealed that the questionnaire was easy to administer and the acceptability was good. The internal consistency and the test-retest reliability were 0.9 and 0.88, respectively. All items were significantly correlated with the total score and the SF-12 used in the study. The CFA with one factor model was good, and for the unidimensional construct, the PSI was found to be 0.902. CONCLUSION: The French version of the Q LES-Q-SF yielded valid and reliable clinical assessments of the quality of life for future research and clinical practice involving French substance abusers. In response to recent questioning regarding the unidimensionality or bidimensionality of the instrument and according to the underlying theoretical unidimensional construct used for its development, this study suggests the Q-LES Q-SF as a one-dimension questionnaire in French QoL studies. PMID- 25113239 TI - Chaotic oscillation and random-number generation based on nanoscale optical energy transfer. AB - By using nanoscale energy-transfer dynamics and density matrix formalism, we demonstrate theoretically and numerically that chaotic oscillation and random number generation occur in a nanoscale system. The physical system consists of a pair of quantum dots (QDs), with one QD smaller than the other, between which energy transfers via optical near-field interactions. When the system is pumped by continuous-wave radiation and incorporates a timing delay between two energy transfers within the system, it emits optical pulses. We refer to such QD pairs as nano-optical pulsers (NOPs). Irradiating an NOP with external periodic optical pulses causes the oscillating frequency of the NOP to synchronize with the external stimulus. We find that chaotic oscillation occurs in the NOP population when they are connected by an external time delay. Moreover, by evaluating the time-domain signals by statistical-test suites, we confirm that the signals are sufficiently random to qualify the system as a random-number generator (RNG). This study reveals that even relatively simple nanodevices that interact locally with each other through optical energy transfer at scales far below the wavelength of irradiating light can exhibit complex oscillatory dynamics. These findings are significant for applications such as ultrasmall RNGs. PMID- 25113240 TI - A mini me?: exploring early childhood diet with stable isotope ratio analysis using primary teeth dentin. AB - OBJECTIVES: Reconstruct childhood diet using teeth collected in Edmonton in a collaborative effort between the Departments of Dentistry and Anthropology at the University of Alberta. METHODS: Deciduous teeth needing extraction were collected from 33 children for stable isotope ratio analysis of diet. Tooth dentin was microsampled in three locations using a newly developed technique to reconstruct the changing pattern of participants' diet through early childhood including breastfeeding practices. RESULTS: The microsampling method can reconstruct diet with tiny samples (0.3 mg). The results reconstruct fetal isotope ratios, which showed significant variation. delta(15)N values indicate some children were being breastfed (7/17), while others were likely bottle fed (10/17). Surprisingly, the early childhood results do not show the range of diets expected in adults based on known eating habits. Toddler diets form a tight cluster implying diets of similar isotopic composition in almost all of the households despite potential cultural and class distinctions (delta(15)N values 11-11.50/00, delta(13)C values around -180/00). The delta(13)C values show a strong C3 dependence for most children, a two outliers show C4 (-120/00) dependence indicating a possible corn based diet. CONCLUSIONS: Microsampling can potentially track each child's diet through early childhood. For this group of children, both breastfeeding and bottle feeding was practiced. However, the percent of breastfed infants was less than reported Canadian rates. Surprisingly, the choice to breastfeed or to bottle feed was not linked to the choice of toddler diet. All toddler diets were narrower in scope than adult diets. PMID- 25113238 TI - Predictors of changes in physical, psychosocial, sexual quality of life, and comfort with food after obesity surgery: a 12-month follow-up study. AB - PURPOSE: Although obesity surgery provides significant postoperative improvement in quality of life (QoL), it is still unclear which factors might predict improvement in QoL after surgery. We aimed to determine which factors might predict changes in physical, psychosocial, sexual QoL, and comfort with food 12 months after surgery, by putting to the test a QoL model based on Wilson and Cleary's model. METHODS: We included 126 obese patients (48.4% had gastric banding, 34.1% had sleeve gastrectomy, and 17.5% had gastric bypass). At baseline, we assessed QoL (Quality of Life, Obesity and Dietetics rating scale), BMI, depression (Beck Depression Inventory), and binge eating (Bulimic Investigatory Test, Edinburgh). At 12 months, we assessed QoL and BMI. To determine the predictors for changes in each QoL dimension after surgery, we used linear mixed models adjusted for preoperative age, BMI, time, type of surgery, preoperative binge eating severity, and preoperative depression severity. RESULTS: After 12 months, we found significant improvement in physical, psychosocial, sexual QoL, but not in comfort with food. Increased weight loss was associated with better improvement in physical and psychosocial QoL. Higher preoperative depression severity predicted poorer improvement in physical, psychosocial, and sexual QoL. Higher preoperative binge eating severity predicted poorer improvement in psychosocial, sexual QoL, and comfort with food. CONCLUSIONS: In addition to weight loss, preoperative levels of binge eating and depression should be considered as important predictors for QoL changes after bariatric surgery. Screening and treatment for preoperative depression and binge eating might improve QoL after bariatric surgery. PMID- 25113241 TI - Effect of clodronate treatment on risk of fracture: a systematic review and meta analysis. AB - A systematic review and a meta-analysis of data of literature were performed to evaluate the efficacy of clodronate in the reduction of risk of fractures in patients with osteoporosis or tumour diseases. A systematic review was conducted to identify original articles, reviews, and any other literature report suitable for the purposes of the meta-analysis, limited to prospective randomized trials that included a placebo or an untreated control arm. The search has identified 18 trials, 13 of which in patients with cancer diseases (breast cancer and multiple myeloma were prevalent), 4 in patients with osteoporosis/low BMD, and 1 in elderly women living in community. A placebo control arm was used in 13 trials. Treatment and follow-up duration ranged from 3 months to 5 years. The meta analysis showed that treatment with clodronate was associated with a reduction of the probability of new fractures compared with controls (OR = 0.572, 95% CI 0.465 0.704 for new vertebral fractures; OR = 0.668, 95% CI 0.494-0.905 for new non vertebral fractures; and OR = 0.744, 95% CI 0.635-0.873 for new overall fractures in those articles where vertebral and non-vertebral new fractures were not considered separately). Similar findings were observed in the separate analysis in patients with cancer forms or osteoporosis. The results of the meta-analysis have demonstrated that clodronate is effective in reducing the risk of vertebral, non-vertebral, and overall fractures in patients with skeletal fragility. PMID- 25113242 TI - The relevance of rhythmical alternation in language processing: an ERP study on English compounds. AB - This study investigates the influence of rhythmic expectancies on language processing. It is assumed that language rhythm involves an alternation of strong and weak beats within a linguistic domain. Hence, in some contexts rhythmically induced stress shifts occur in order to comply with the Rhythm Rule. In English, this rule operates to prevent clashes of stressed adjacent syllables or lapses of adjacent unstressed syllables. While previous studies investigated effects on speech production and perception, this study focuses on brain responses to structures either obeying or deviating from this rule. Event-related potentials show that rhythmic regularity is relevant for language processing: rhythmic deviations evoked different ERP components reflecting the deviance from rhythmic expectancies. An N400 effect found for shifted items reflects higher costs in lexical processing due to stress deviation. The overall results disentangle lexical and rhythmical influences on language processing and complement the findings of previous studies on rhythmical processing. PMID- 25113243 TI - The Sphagnum microbiome supports bog ecosystem functioning under extreme conditions. AB - Sphagnum-dominated bogs represent a unique yet widely distributed type of terrestrial ecosystem and strongly contribute to global biosphere functioning. Sphagnum is colonized by highly diverse microbial communities, but less is known about their function. We identified a high functional diversity within the Sphagnum microbiome applying an Illumina-based metagenomic approach followed by de novo assembly and MG-RAST annotation. An interenvironmental comparison revealed that the Sphagnum microbiome harbours specific genetic features that distinguish it significantly from microbiomes of higher plants and peat soils. The differential traits especially support ecosystem functioning by a symbiotic lifestyle under poikilohydric and ombrotrophic conditions. To realise a plasticity-stability balance, we found abundant subsystems responsible to cope with oxidative and drought stresses, to exchange (mobile) genetic elements, and genes that encode for resistance to detrimental environmental factors, repair and self-controlling mechanisms. Multiple microbe-microbe and plant-microbe interactions were also found to play a crucial role as indicated by diverse genes necessary for biofilm formation, interaction via quorum sensing and nutrient exchange. A high proportion of genes involved in nitrogen cycle and recycling of organic material supported the role of bacteria for nutrient supply. 16S rDNA analysis indicated a higher structural diversity than that which had been previously detected using PCR-dependent techniques. Altogether, the diverse Sphagnum microbiome has the ability to support the life of the host plant and the entire ecosystem under changing environmental conditions. Beyond this, the moss microbiome presents a promising bio-resource for environmental biotechnology - with respect to novel enzymes or stress-protecting bacteria. PMID- 25113244 TI - The relationship between glucocorticoid receptor polymorphisms, stressful life events, social support, and post-traumatic stress disorder. AB - BACKGROUND: It is debatable whether or not glucocorticoid receptor (GR) polymorphisms moderate susceptibility to PTSD. Our objective was to examine the effects of stressful life events, social support, GR genotypes, and gene environment interactions on the etiology of PTSD. METHODS: Three tag single nucleotide polymorphisms, trauma events, stressful life events, and social support were assessed in 460 patients with PTSD and 1158 control subjects from a Chinese Han population. Gene-environment interactions were analyzed by generalized multifactor dimensionality reduction (GMDR). RESULTS: Variation in GR at rs41423247 and rs258747, stressful life events, social support, and the number of traumatic events were each separately associated with the risk for PTSD. A gene-environment interaction among the polymorphisms, rs41423247 and rs258747, the number of traumatic events, stressful life events, and social support resulted in an increased risk for PTSD. High-risk individuals (a large number of traumatic events, G allele of rs258747 and rs41423247, high level stressful life events, and low social support) had a 3.26-fold increased risk of developing PTSD compared to low-risk individuals. The association was statistically significant in the sub-groups with and without childhood trauma. CONCLUSIONS: Our data support the notion that stressful life events, the number of trauma events, and social support may play a contributing role in the risk for PTSD by interacting with GR gene polymorphisms. PMID- 25113245 TI - Incidence and risk factors for AIDS-related mortality in HIV patients in China: a cross-sectional study. AB - BACKGROUND: To estimate the incidence and risk factors for mortality in HIV-1 infected patients in China. METHODS: Information on AIDS-related deaths was collected from the Chinese Center for Disease Control and Prevention's Disease Surveillance Information Reporting System and AIDS Prevention and Control Information System. RESULTS: A total of 379,348 HIV cases were recorded in the databases from 2006. Among those, 138,288 patients were reported as having developed AIDS and 72,616 (19%) died of AIDS after data was extracted from the databases in January 2011. Mortality was higher among those patients aged 50 years old or older (AOR: 3.41, CI: 1.47-7.91) who had been infected by intravenous drug use (AOR: 1.65, CI: 1.28-2.14) or blood transfusion/donation (AOR: 2.18: 1.18-3.99). Compared to patients who had not initiated highly active antiretroviral therapy (HAART), those who had initiated HAART were more likely to have a long interval of time between infection confirmation and AIDS-related death. CONCLUSIONS: The effective reduction of AIDS mortality could be improved through timely treatment. PMID- 25113246 TI - Intravitreal bevacizumab versus posterior subtenon triamcinolone in diffuse diabetic macular edema. AB - The aim of the study was to compare intravitreal bevacizumab (IVB) and posterior subtenon triamcinolone (PST) as an adjunct to laser treatment in diffuse diabetic macular edema (Diffuse DME). Prospective-randomized control trial of 30 eyes of 30 diabetic patients having Diffuse DME with maximum retinal thickness (MRT) was more than or equal to 350 um. The subjects were randomly allocated into two groups. Group A (12 eyes) received IVB and group B received PST (18 patients) before laser treatment. Grid laser treatment was done when the MRT decreased to less than 350 um. OCT thickness-guided repeat injections were given if required. The patients had minimum follow-up of 6 months. At 6-month follow-up, the two groups were compared for (1) Maximum change in visual acuity letter score using logMAR chart (2) Reduction in MRT on OCT. The mean logMAR visual acuity at baseline was 0.63 +/- 0.45 (0-1.6) in group A and was 0.76 +/- 0.38 (0.2-1.3) in group B. The mean logMAR visual acuity at 6 month in group A was 0.34 +/- 0.21 (0 0.6) and in group B was 0.64 +/- 0.37 (0.3-1.3). The mean visual acuity at last follow-up was significantly better in group A than group B (p = 0.02). The mean change in MRT in Group A and Group B was 177.8 +/- 85.64 and 156.07 +/- 102.86, respectively, which was significantly better than the baseline in both the groups and was comparable in both groups. The study provides evidence to support the use of IVB over PST in diffuse diabetic macular edema. PMID- 25113247 TI - Au@Pt nanoparticle encapsulated target-responsive hydrogel with volumetric bar chart chip readout for quantitative point-of-care testing. AB - Point-of-care testing (POCT) with the advantages of speed, simplicity, portability, and low cost is critical for the measurement of analytes in a variety of environments where access to laboratory infrastructure is lacking. While qualitative POCTs are widely available, quantitative POCTs present significant challenges. Here we describe a novel method that integrates an Au core/Pt shell nanoparticle (Au@PtNP) encapsulated target-responsive hydrogel with a volumetric bar-chart chip (V-Chip) for quantitative POCT. Upon target introduction, the hydrogel immediately dissolves and releases Au@PtNPs, which can efficiently catalyze the decomposition of H2 O2 to generate a large volume of O2 to move of an ink bar in the V-Chip. The concentration of the target introduced can be visually quantified by reading the traveling distance of the ink bar. This method has the potential to be used for portable and quantitative detection of a wide range of targets without any external instrument. PMID- 25113248 TI - Focal adhesion kinase inhibitors in the treatment of metastatic cancer: a patent review. AB - INTRODUCTION: Focal adhesion kinase (FAK) plays a prominent role in integrin signaling. FAK activation increases phosphorylation of Tyr397 and other sites of the protein. FAK-dependent activation of signaling pathways implicated in controlling essential cellular functions including growth, proliferation, survival and migration. FERM (F for the 4.1 protein, ezrin, radixin and moesin) domain-enhanced p53 degradation plays a critical role in proliferation and survival. FAK, overexpressed in metastatic tumors, has emerged as an important therapeutic target for the development of selective inhibitors. FAK inhibitors achieved tumor growth inhibition and induced apoptosis. Strategies targeting FAK inhibition using novel compounds have created an exciting opportunity for anticancer therapy. AREAS COVERED: This review summarizes the current research with available data from early phase clinical trials and discusses the available small-molecule inhibitors of FAK from patents. The importance of inhibiting FAK activity in cancer patients is discussed. EXPERT OPINION: Emerging data from clinical trials with orally available small-molecule inhibitors of FAK are promising. Although this approach is appropriate as a targeted therapeutic approach against several metastatic cancer types, several compounds in research are yet to prove their preclinical efficacy. This report lays special emphasis on the available patent data of FAK inhibitors for such targeted molecular therapies. This review summarizes current knowledge about FAK inhibition in cancer therapy. PMID- 25113249 TI - The prognosis significance of TGF-beta1 and ER protein in cervical adenocarcinoma patients with stage Ib~IIa. AB - The incidence of stage Ib~IIa of cervical adenocarcinoma accounts about 60 to 70% of all patients. This study aims to investigate the prognostic significance of protein estrogen receptor alpha (ERalpha) and transforming growth factor beta 1 (TGF-beta1) level in different glandular epithelia of the cervix. In this study, immunohistochemistry was used to detect ERalpha and TGF-beta1 in carcinomas and incisal margins of 66 cases with cervical adenocarcinoma, 20 cases with normal cervix, and 20 cases with chronic cervicitis. Uni- and multivariate analysis was applied to evaluate the prognostic significance of TGF-beta1 and ERalpha in carcinomas. The results indicated that the positive expression of TGF-beta1 in carcinomas was 71.21%, significantly higher compared to that in the normal cervix (35%) and chronic cervicitis (55%) (chi(2) = 8.901, P = 0.012). Similarly, the positive expression of ERalpha in the carcinomas was 68.18%, significantly higher compared to the normal cervix (35%) and chronic cervicitis (50%) (chi(2) = 7.693, P = 0.021). Both TGF-beta1 and ERalpha in the carcinomas were associated with the vaginal recurrence, infection of HPV, depth of infiltration, and lymphatic metastasis (P < 0.05). The conjugation of TGF-beta1 and ERalpha was an independent prognostic factor for cervical adenocarcinoma. Survival curve showed that the positive TGF-beta1 and ERalpha indicated a short lifetime of patient with cervical adenocarcinoma. In conclusion, the expression of TGF-beta1 and ERalpha protein in the carcinomas had a significant prognostic value in a patient of stage Ib~IIa in cervical adenocarcinoma. PMID- 25113250 TI - Fucoxanthin induces apoptosis in human cervical cancer cell line HeLa via PI3K/Akt pathway. AB - Cervical cancer (CC) is a malignant neoplasm arising from cells originating in the cervix uteri, among the top causes of death from cancer in women. In a gene expression profiling study of metabolic response to treatment, PI3K/Akt signaling pathway are associated with the development of CC. A common mechanism of Akt activation seen in cancer types is alterations in the upstream regulators of Akt such as phosphatidylinositol 3-kinase (PI3K), which is overexpressed in cervical cancer tissues, and leads to phosphorylation of Akt. Both PI3K and Akt inhibitors exist and may be therapeutically valuable. In the present study, we use MTT assay and western blot for the high-throughput screening to select specific inhibitors of PI3K/Akt signaling pathway, and then obtain fucoxanthin. Fucoxanthin is a water-soluble dietary fiber, taken from the unique slimy component of alginic cells. Various studies have pointed out that fucoxanthin is very effective for the treatment of cancer. Our results have shown that fucoxanthin induced a significant apoptosis of HeLa cells, compared with other candidates. After treatment with fucoxanthin for 24 h, the level of phosphorylation was inhibited in a dose-dependent manner, and the proteins of apoptotic markers were changed in HeLa cells. And fucoxanthin could suppress tumor growth in vivo. In addition, the mitochondrial signal transduction pathway maybe was involved in its mechanism and NF-kappaB activation was decreased after treatment with fucoxanthin. Therefore, fucoxanthin may be used as anti-cervical cancer drugs in the future. PMID- 25113251 TI - Association between the XPD/ERCC2 Lys751Gln polymorphism and risk of cancer: evidence from 224 case-control studies. AB - Genetic variations in the xeroderma pigmentosum group D (XPD) gene may increase cancer susceptibility by affecting the capacity for DNA repair. A lot of studies have reported the association of XPD Lys751Gln polymorphism with risk of cancer, but the results remained controversial. Hence, we performed a systematic review and conducted a meta-analysis to explore association of the XPD Lys751Gln polymorphism with risk of cancer (78,398 cases and 103,178 controls from 224 studies). Overall, a significantly increased cancer risk was found in all genetic models (dominant model: odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.06-1.14; recessive model: OR = 1.10, 95% CI = 1.05-1.15; homozygous model: OR = 1.14, 95% CI = 1.08-1.21; heterozygous model: OR = 1.09, 95% CI = 1.05-1.12; additive model: OR = 1.08, 95% CI= 1.05-1.11) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk of cancer remained for subgroups of breast cancer, esophageal cancer, hepatocellular cancer, leukemia, lung cancer, and melanoma. In summary, this meta-analysis suggests the XPD Lys751Gln polymorphism is a genetic susceptibility for some cancer types. Moreover, ethnicity, histological type of cancer, and smokers seem to contribute to varying expressions of the Lys751Gln on some cancer risk. In addition, our work also points out the importance of new studies for Lys751Gln association in endometrial cancer and ovarian cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the Lys751Gln polymorphism in cancer development. PMID- 25113252 TI - COX-2 overexpression and -8473 T/C polymorphism in 3' UTR in non-small cell lung cancer. AB - A new class of compounds targeting cyclooxygenase 2 (COX-2) together with other different clinically used therapeutic strategies has recently shown a promise for the chemoprevention of several solid tumors including lung cancer. The aim was to study the possible role of COX-2 -8473 T/C NP and its expression in the pathogenesis of non-small cell lung cancer. One hundred ninety non-small cell lung cancer (NSCLC) patients and 200 healthy age-, sex-, and smoking-matched controls were used for polymorphic analysis, and 48 histopathologically confirmed NSCLC patients were analyzed for COX-2 messenger RNA (mRNA) and protein expression. Our results showed that the frequencies of variant genotypes 8473 CT/CC were significantly less common in the cases (30.0%) than in the controls (36%), suggesting that the 8473 C variant allele is related with lower susceptibility in NSCLC (OR = 0.79, 95% CI 0.54-1.4). However, the frequency of COX-2 -8473 TC and CC genotypes were significantly associated with age in NSCLC (P = 0.02). Quantitative real-time expression analysis showed a significant increase in the COX-2 mRNA in tumor tissues as compared to their adjacent normal tissues [delta cycle threshold (DeltaCT) = 9.25 +/- 4.67 vs 5.63 +/- 3.85, P = 0.0001]. Multivariate logistic regression analyses revealed that the COX-2 expression was associated significantly with age (P = 0.044). Also, an increasing trend was observed in stages I and II and in female patients compared to stages III and IV and male patients, respectively, but no statistical significance was observed. However, COX-2 mRNA expression shown no association with the -8473 C variant allele. Our findings indicate that the COX-2 T8473C polymorphism may contribute to NSCLC cancer susceptibility in the Kashmiri population, while our expression analysis revealed a significant increase of COX-2 in tumor tissues as compared to their adjacent normal tissues, suggesting that it could become an important therapeutic marker in NSCLC in the future. PMID- 25113253 TI - Vascular marker expression during the development of various types of gynaecological malignancy. AB - Clinical diagnosis of gynaecological malignancies is usually successful in the advanced stages of the tumour, and this has a major impact on the success of therapy. Therefore, in the last few years, cancer research has tried to identify and characterise new biochemical and molecular markers needed as predictive indicators for the diagnosis of cancer. Our aim has been to search the molecular changes in gene expression of death receptor 6, glycoprotein M6B (Gpm6B) and genes associated with tumours of the female genital system. After isolation of messenger RNA (mRNA), transcription of mRNA into the cDNA was performed. The quantification of gene expression changes was detected using the reverse transcription polymerase chain reaction (RT-PCR) method. Analysis at the protein level was performed using the Western blot method. In both methods, we used actin as a housekeeping gene for normalisation. Numerical quantification of changes in expression and in the level of the specific proteins was evaluated using the Data Syngene program. Significant changes in the levels of protein and mRNA expression were detected, mainly in the death receptor 6 (Dr6) gene of patients suffering from cancer of the corpus and cervix uteri and ovarian cancer, which also corresponded with the level of protein Dr6. At the level of transcription, a significant increase in the expression levels of mRNA for the Gpm6B gene was detected, which led to an increase in corresponding protein in the peripheral blood of patients with gynaecological tumours against the healthy control group. This article could help to find an adequate marker for clinical application that will enable more sensitive detection of the early stages of gynaecological malignancies from the peripheral blood of patients. PMID- 25113256 TI - Core outcomes for reporting women's health. PMID- 25113255 TI - Comment on Zhuang YF et al.: impact of vascular endothelial growth factor expression on overall survival in patients with osteosarcoma: a meta-analysis. PMID- 25113254 TI - A functional and protein-protein interaction analysis of neuroepithelial cell transforming gene 1 in hepatocellular carcinoma. AB - In our previous study, we reported that the expression of neuroepithelial transforming gene 1 (NET1) was increased in hepatocellular carcinoma (HCC) tissues and suggested that NET1 may serve as a novel prognostic predictor and a useful target for HCC therapy. The aim of this study was to determine the role of NET1 in HCC by monitoring the proliferation, migration, invasion, and metastasis of HCC cells in which NET1 has been stably knocked down. Additionally, to provide targets for therapeutic intervention, we aimed to identify the protein which interacts with NET1. NET1 knockdown significantly reduced the migration, invasion, and metastasis of MHCC-97H cells by 44, 65, and 77%, respectively, while cell proliferation was not significantly altered following NET1 knockdown. During our efforts to find potential NET1 modulators through protein-protein interactions, we identified merlin as a NET1-binding protein in a yeast two hybrid screen. The interaction between NET1 and merlin was confirmed by co immunoprecipitation. We found that the levels of NET1 protein decreased along with the increase of merlin levels. Furthermore, we demonstrated that merlin facilitates NET1 ubiquitination via the ubiquitin-proteasome pathway. Taken together, this study suggests that NET1 plays an important role in HCC cell migration, invasion, and metastasis, which are key aspects of HCC progression. Furthermore, merlin may serve as a tumor suppressor for HCC by facilitating ubiquitination of NET1. PMID- 25113258 TI - Intraoperative powdered vancomycin use with paddle lead placement. AB - OBJECTIVES: This is a prospective case-control study that was conducted to determine if the addition of intraoperative powdered vancomycin placed directly into the wounds at the time of closure might decrease the rate of acute postoperative infection after the placement of spinal cord stimulator paddle leads. MATERIALS AND METHODS: A retrospective analysis of the author's practice from January 1, 2009 through July 31, 2012 (Table 1) showed that those patients requiring a laminectomy instead of a laminotomy to insert a paddle lead had an increased rate of acute postop infection. All patients receiving a thoracic spinal cord stimulator paddle from January 1, 2013 through December 31, 2013 were then followed prospectively. Those patients whose paddle leads could be inserted with a laminotomy were treated in a standard fashion. Those patients who required a laminectomy for insertion of the paddle lead received powdered vancomycin placed directly into the wounds prior to closure. RESULTS: One hundred and nine patients underwent implantation of a permanent spinal cord stimulator paddle lead and battery between January 1 and December 31, 2013. Thirty-two of those patients required a laminectomy for implantation of the paddle and received intraoperative powdered vancomycin placed directly into both wounds at the time of closure. The remaining 77 patients were treated in a standard fashion. There were no infections in the laminectomy group and two infections in the laminotomy group. CONCLUSION: This study indicates that intraoperative powdered vancomycin placed directly into the wounds at the time of closure can produce similar infection rates between the groups of patients requiring a laminectomy vs. a laminotomy for implantation of a thoracic paddle lead. These findings need confirmation by a randomized controlled design study. PMID- 25113257 TI - Cystoprostatectomy versus prostatectomy alone for locally advanced or recurrent pelvic cancer. AB - BACKGROUND: There is minimal published data evaluating the oncological outcome of rectal resection with prostatectomy alone versus rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer. This study aims to evaluate the oncological and functional outcomes of performing rectal resection with prostatectomy alone compared with rectal resection with cystoprostatectomy in patients undergoing pelvic exenteration. METHODS: Consecutive patients undergoing pelvic exenteration for locally advanced or recurrent pelvic cancer between 1998 and 2012 were identified from a prospectively maintained database. Patients undergoing rectal resection with prostatectomy alone were compared with a control group who underwent rectal resection with cystoprostatectomy and urostomy formation. The primary outcome was overall survival. Secondary outcomes analysed in the prostatectomy group included completeness of resection, continence and erectile function. RESULTS: Eleven rectal resections with prostatectomy were compared with 20 rectal resections with cystoprostatectomy. R0 resection was achieved in 73 and 65% respectively. There was no difference in overall survival (P = 0.40). Urinary continence was achieved in 36% of prostatectomy alone patients, while 27% experienced mild incontinence. Erectile function was poor, with only one patient able to maintain normal erections. CONCLUSION: In appropriately selected patients with invasive pelvic tumours, rectal resection with prostatectomy alone provides adequate oncological outcomes. The ability to achieve an R0 resection was not compromised and overall survival is comparable with cystoprostatectomy. Urinary function is reasonable in most patients, although sexual function is compromised in almost all. PMID- 25113259 TI - Clinical and radiologic evaluation of arthroscopic medial meniscus root tear refixation: comparison of the modified Mason-Allen stitch and simple stitches. AB - PURPOSE: This study compared the clinical and radiologic outcomes of arthroscopic medial meniscus root refixation using the modified Mason-Allen stitch and simple stitches. METHODS: The outcomes of 25 patients who underwent arthroscopic meniscus root refixation using the modified Mason-Allen stitch (M group) between June 2010 and January 2012 were compared with those of 25 matched control patients (S group) who underwent meniscus root refixation using simple stitches between March 2004 and August 2007. The Lysholm score, International Knee Documentation Committee Subjective Knee Form score, joint space narrowing, and Kellgren-Lawrence grade were assessed. Medial meniscal extrusion, progression of cartilage degeneration, and healing status of the refixed medial meniscus root were assessed on magnetic resonance images. RESULTS: No between-group difference was found in age, sex, body mass index, or preoperative patient characteristics. The mean follow-up times for the M and S groups were 24.1 and 25.9 months (P = .248), respectively. The Lysholm, International Knee Documentation Committee Subjective Knee Form, and Tegner activity scores improved significantly in both groups. The repaired root tended to heal better in the M group than in the S group (P = .065). Although the postoperative clinical outcomes did not differ between the groups, postoperative medial meniscal extrusion decreased -0.6 +/- 0.9 mm in the M group and increased 1 +/- 0.6 mm in the S group on magnetic resonance imaging (P < .001). The M group did not show significant progression in the Kellgren-Lawrence grade and cartilage degeneration (P = .083 and P = .317, respectively), whereas both measures increased significantly in the S group (P = .008 and P < .001, respectively). CONCLUSIONS: Compared with simple stitches, the modified Mason-Allen stitch improved the degree of meniscal extrusion, although the 2 different suture techniques showed no difference in clinical outcomes at short-term follow-up. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 25113261 TI - Resistance to the antiproliferative effect induced by a short-chain ceramide is associated with an increase of glucosylceramide synthase, P-glycoprotein, and multidrug-resistance gene-1 in cervical cancer cells. AB - PURPOSE: Ceramide is glycosylated to glucosylceramide or lactosylceramide, and this glycosylation is a novel multidrug-resistance (MDR) mechanism. In this work, a short-chain ceramide (C6), lactosylceramide (LacCer), and an inhibitor of ceramide glycosylation (D-threo-1-phenyl-2-decanoylamino-3-1-propanol, PDMP) were evaluated on the proliferation of cervical cancer cells. The participation of glucosylceramide synthase (GCS), P-glycoprotein (P-gp), and multidrug-resistance gene-1 (MDR-1) in the resistance to the antiproliferative effect induced by C6 was also evaluated. METHODS: Cell proliferation was determined by crystal violet staining. GCS and MDR-1 mRNA expression was evaluated by real-time RT-PCR assay. GCS and P-gp protein expressions, as well as Rhodamine 123 uptake, which is a functional test for P-gp efflux activity, were determined by flow cytometry. RESULTS: C6 inhibited proliferation of CaLo and CasKi cells with an IC50 of 2.5 MUM; however, 50% proliferation of ViBo cells was inhibited with 10 MUM. LacCer increased the proliferation of all cells. When cells were treated with PDMP plus C6, no additional effect on antiproliferation induced by C6 was observed in CaLo and CasKi cells; however, proliferation diminished in comparison with C6 alone in ViBo cells. C6 increased GCS and MDR-1 expression in all cells, as well as P-gp expression in CasKi cells. CONCLUSIONS: Cells that have more capacity to glycosylate ceramide and express a higher level of GCS, MDR-1, and P-gp, are more resistant to the antiproliferative effect induced by C6. PMID- 25113262 TI - Combined effects of the cyanobacterial toxin microcystin-LR and environmental factors on life-history traits of indigenous cladoceran Moina macrocopa. AB - Environmental factors are important in that they might interact with toxicants and could affect the concentration-response relationship of the toxicants in the water environment. Microcystins (MCs) produced by algal blooming are natural toxins that exert severe impacts on aquatic organisms. Despite the possibility of interaction effects between environmental factors and MCs, very few studies have been carried out to date. In the present study, the authors evaluated the effect of 3 environmental factors on chronic toxicity of MC-leucine-arginine (MC-LR; 0 ug/L, 0.8 ug/L, 4 ug/L, 20 ug/L, 100 ug/L, 500 ug/L) to the freshwater invertebrate Moina macrocopa. Three environmental factors were determined to reflect the reasonable worst conditions of the water body in South Korea: high water temperature (25 degrees C), the highest concentration of nutrients (ammonia-nitrogen [NH3 -N] = 3.8 mg/L; nitrate-nitrogen [NO3 -N] = 8.5 mg/L) during the occurrence of algal bloom, and 2 pH conditions of 7.0 and 9.0, which satisfy the test acceptance criteria for the Daphnia test. Among the various environmental factors being tested, high water temperature and NO3 -N elevated chronic toxicity of MC-LR, whereas NH3 -N reduced toxicity. Water pH did not influence chronic toxicity of MC-LR to M. macrocopa. This observation suggests that those environmental factors are responsible for changing the trend of MC-LR toxicity. PMID- 25113263 TI - Hydrogel doped with nanoparticles for local sustained release of siRNA in breast cancer. AB - Of all the much hyped and pricy cancer drugs, the benefits from the promising siRNA small molecule drugs are limited. Lack of efficient delivery vehicles that would release the drug locally, protect it from degradation, and ensure high transfection efficiency, precludes it from fulfilling its full potential. This work presents a novel platform for local and sustained delivery of siRNA with high transfection efficiencies both in vitro and in vivo in a breast cancer mice model. siRNA protection and high transfection efficiency are enabled by their encapsulation in oligopeptide-terminated poly(beta-aminoester) (pBAE) nanoparticles. Sustained delivery of the siRNA is achieved by the enhanced stability of the nanoparticles when embedded in a hydrogel scaffold based on polyamidoamine (PAMAM) dendrimer cross-linked with dextran aldehyde. The combination of oligopeptide-terminated pBAE polymers and biodegradable hydrogels shows improved transfection efficiency in vivo even when compared with the most potent commercially available transfection reagents. These results highlight the advantage of using composite materials for successful delivery of these highly promising small molecules to combat cancer. PMID- 25113260 TI - Impact of transpulmonary thermodilution-based cardiac contractility and extravascular lung water measurements on clinical outcome of patients with Takotsubo cardiomyopathy after subarachnoid hemorrhage: a retrospective observational study. AB - INTRODUCTION: Takotsubo cardiomyopathy (TCM) is a life-threatening systemic consequence early after subarachnoid hemorrhage (SAH), but precise hemodynamics and related outcome have not been studied. The purpose of this study was to investigate the TCM-induced cardiac function by transpulmonary thermodilution and its impact on clinical outcome of SAH. METHODS: We retrospectively analyzed 46 consecutive postoperative SAH patients who developed TCM. Patients were divided into two groups of echocardiographic left ventricular ejection fraction (LVEF) < 40% (TCM with left ventricular (LV) dysfunction) and LVEF >=40% (TCM without LV dysfunction). Cardiac function index (CFI) and extravascular lung water index (ELWI) were monitored by transpulmonary thermodilution, in parallel with serial measurements of echocardiographic parameters and blood biochemical markers. RESULTS: Transpulmonary thermodilution-derived cardiac function index (CFI) was significantly correlated with (LVEF) (r = 0.82, P < 0.0001). The CFI between day 0 to day 7 was significantly lower in patients with LV dysfunction (LVEF <40%) than in patients with LVEF >=40% (P < 0.05). CFI had a better ability than cardiac output to detect cardiac dysfunction (LVEF < 40%) (area under the curve: 0.85 +/- 0.02; P < 0.001). A CFI value of < 4.2 min-1 had a sensitivity of 82% and specificity of 84% for detecting LVEF <40%. The CFI < 4.2 min-1 was associated with delayed cerebral ischemia (DCI) (odds ratio (OR), 2.14; 95% confidence interval (CI), 1.33-2.86; P = 0.004) and poor 3-month functional outcome on modified Rankin Scale of 4-6 (OR, 1.87; 95% CI, 1.06-3.29; P = 0.02). An extravascular lung water index (ELWI) > 14 mL/kg after day 4 increased the risk of poor functional outcome at 3-month follow-up (OR, 2.10; 95% CI, 1.11 3.97; P = 0.04). CONCLUSIONS: Prolonged cardiac dysfunction and pulmonary edema increased the risk of DCI and poor 3-month functional outcome in patients with SAH suffering from TCM. Serial measurements of CFI and ELWI by transpulmonary thermodilution may provide an easy bedside method of detecting early changes of the cardiopulmonary function in directing proper post-SAH treatment. PMID- 25113265 TI - Editor's Spotlight/Take 5: Small improvements in mechanical axis alignment achieved with MRI versus CT-based patient-specific instruments in TKA: a randomized clinical trial. PMID- 25113267 TI - Letter to the editor: anconeus interposition arthroplasty: mid- to long-term results. PMID- 25113266 TI - Does patient sex affect the anatomic relationships between the sternoclavicular joint and posterior vascular structures? AB - BACKGROUND: Despite increased concern for injury during surgical reconstruction of the sternoclavicular joint, to our knowledge there are few studies detailing the vascular relationships adjacent to the joint. QUESTIONS/PURPOSES: We investigated sex differences in the following relationships for sternoclavicular joint reconstruction: (1) safe distance from the posterior surface of the medial clavicle's medial and lateral segments to the major vessels, (2) length of the first costal cartilage and safe distance from the first rib to the internal mammary artery, (3) minimum distance medial to the sternoclavicular joint for optimal hole placement, and (4) safe distance from the manubrium to the great vessels. METHODS: Fifty normal postcontrast CT scans of the chest were reviewed. Means, standard deviations, and 95% CI were calculated for each aforementioned measurement. A t-test was used to determine if a sex difference exists (p<=0.05). RESULTS: At the medial end of the clavicle, the safe distance from the medial segment (first 10 mm) to the major vessels was greater in males than in females (3.5 mm versus 2.4 mm, respectively; 95% CI, 3 mm-4 mm versus 1.7 mm-3 mm, respectively; p=0.014). For the lateral segment (next 10 mm), the distance also was safer in males than in females (3.3 mm versus 1.7 mm, respectively; 95% CI, 2.7 mm-4 mm versus 1.1 mm-2.3 mm, respectively; p<0.001). The mean length of the first costal cartilage also was greater in males (35.8 mm versus 30.1 mm, respectively; 95% CI, 33.8 mm-37.8 mm versus 28.5 mm-31.9 mm, respectively; p<0.001); the distance from the first costochondral joint to the internal mammary artery was safer in males than in females (19.1 mm versus 15.4 mm, respectively; 95% CI, 16.5 mm-21.8 mm versus 13 mm-17.9 mm, respectively; p=0.05). The minimum distance to avoid inadvertent penetration of the sternoclavicular joint was greater in males than in females (16 mm versus 12.3 mm, respectively; 95% CI, 14.6 mm-17.5 mm versus 11 mm-13.6 mm, respectively; p<0.001). The distance to vessels after penetration of the manubrium was not different between males and females (5.6 mm versus 3.9, respectively; 95% CI, 4.4 mm-6.8 mm versus 2.6 mm-5.2 mm, respectively; p=0.06). CONCLUSIONS: This study makes apparent the intimate relationships between vessels and the musculoskeletal structures associated with sternoclavicular reconstruction. Based on our findings, we recommend considering the sex of the patient, using caution when drilling, and protecting essential structures posterior to the joint. PMID- 25113268 TI - What is the work environment of orthopaedic surgeons in China? AB - BACKGROUND: Physicians in China face heavy demands from patients and the government for services but deal with the threat of unpredictable legal and physical conflicts with patients, some ending with the death of doctors. More than 40 doctors and nurses have been killed by patients since 2001. QUESTIONS/PURPOSES: We sought to evaluate (1) the demographics of orthopaedic practice, (2) duty periods, (3) practice support, and (4) job satisfaction among orthopaedic surgeons in China. METHODS: Questionnaires were posted online at www.OrthoChina.org for download by orthopaedic surgeons in 2006 to 2007, and sent to those attending meetings in 2013. In 2013, a total of 1350 surgeons were invited and 456 participated in the survey at meetings. In 2007, during the period of the survey, 9759 individuals were qualified orthopaedic surgeons, and 334 participated in the survey at www.OrthoChina.org . RESULTS: Ninety-one percent of orthopaedic surgeons work in public and 9% in private hospitals. Ninety-four percent work more than 8 hours per day 6 to 7 days a week. Twenty five percent work more than 12 hours per day 6 to 7 days a week without extra compensation. The majority of orthopaedic surgeons must work on national statutory holidays. Almost none received contractually mandated income for weekends and national holidays. Approximately 80% of participants reported an attack of some kind, including physical or psychologic harm. With respect to job satisfaction, 73% stated they would not choose to be a physician again and 86% reported that they do not want their children to become a physician. CONCLUSIONS: China's rapid economic growth and resulting demands for modern health care have resulted in heavy pressure on orthopaedic surgeons, financially and personally. Chinese orthopaedic surgeons are overworked, suffer lack of respect, and face the possibility of serious personal harm. As a consequence, they are demoralized and unsatisfied. Significant reforms are needed. PMID- 25113269 TI - Muscle fibers are injured at the time of acute and chronic rotator cuff repair. AB - BACKGROUND: Rotator cuff tears are a common source of shoulder pain and disability. Even after surgical repair, some patients continue to have reduced function and progression of fatty degeneration. Because patients with chronic cuff tears often experience muscle shortening, it is possible that repairing the tendon to its anatomic footprint induces a stretch-induced muscle injury that could contribute to failures of the repair and perhaps ongoing pain. QUESTIONS/PURPOSES: We hypothesized that, compared with acutely torn and repaired muscles, the stretch that is required to repair a chronically torn cuff would result in more muscle fiber damage. Specifically, we asked: (1) Is there muscle fiber damage that occurs from repair of an acutely torn rotator cuff and does it vary by location in the muscle; and (2) is the damage greater in the case of repair of a chronic injury? METHODS: We used an open surgical approach to create a full-thickness rotator cuff tear in rats, and measured changes in muscle mass, length, and the number of fibers containing the membrane impermeable Evans Blue Dye after acute (1 day) or chronic (28 days) cuff tear or repair in rats. Differences between groups were tested using a one-way ANOVA followed by Tukey's post hoc sorting. RESULTS: Chronic tears resulted in 24% to 35% decreases in mass and a 20% decrease in length. The repair of acutely and chronically torn muscles resulted in damage to 90% of fibers in the distal portion of the muscle. In the proximal portion, no differences between the acutely torn and repaired groups and controls were observed, whereas repairing the chronically torn group resulted in injury to almost 70% of fibers. CONCLUSIONS: In a rat model, marked injury to muscle fibers is induced when the tendons of torn rotator cuffs are repaired to their anatomic footprint. CLINICAL RELEVANCE: In this animal model, we found that repair of chronically torn cuff muscles results in extensive injury throughout the muscle. Based on these findings, we posit that inducing a widespread injury at the time of surgical repair of chronically torn rotator cuff muscles may contribute to the problems of failed repairs or continued progression of fatty degeneration that is observed in some patients that undergo rotator cuff repair. Therapeutic interventions to protect muscle fiber membranes potentially could enhance outcomes for patients undergoing rotator cuff repair. To evaluate this, future studies that evaluate the use of membrane sealing compounds or drugs that upregulate endogenous membrane-sealing proteins are warranted. PMID- 25113270 TI - Total serum transforming growth factor-beta1 is elevated in the entire spectrum of genetic aortic syndromes. AB - BACKGROUND: Total serum transforming growth factor-beta 1 (tsTGF-beta1) is increased in patients with Marfan syndrome (MFS), but it has not been assessed in thoracic aortic aneurysm and dissection (TAAD), Loeys-Dietz syndrome (LDS), and bicuspid aortic valve disease (BAVD). HYPOTHESIS: tsTGF-beta1 is increased in genetic aortic syndromes including TAAD, LDS, MFS, and BAVD. METHODS: We measured tsTGF-beta1 and performed sequencing of the genes FBN1, TGFBR1, and TGFBR2 in 317 consecutive patients with suspected or known genetic aortic syndrome (167 men, 150 women; mean age 43 +/- 14 years). TAAD was diagnosed in 20, LDS in 20, MFS in 128, and BAVD in 30 patients, and genetic aortic syndrome was excluded in 119 patients. RESULTS: Elevated tsTGF-beta1 levels were associated with causative gene mutations (P = 0.008), genetic aortic syndrome (P = 0.009), and sporadic occurrence of genetic aortic syndrome (P = 0.048), whereas only genetic aortic syndrome qualified as an independent predictor of tsTGF-beta1 (P = 0.001). The tsTGF-beta1 levels were elevated in FBN1 and NOTCH1 mutations vs patients without mutations (both P = 0.004), and in NOTCH1 mutations vs ACTA2/MYH11 mutations (P = 0.015). Similarly, tsTGF-beta1 levels were elevated in MFS (P = 0.003) and in BAVD (P = 0.006) vs patients without genetic aortic syndrome. In contrast to specific clinical features of MFS, FBN1 in-frame mutations (P = 0.019) were associated with increased tsTGF-beta1 levels. CONCLUSIONS: tsTGF-beta1 is elevated in the entire spectrum of genetic aortic syndromes. However, gradual differences in the increases of tsTGF-beta1 levels may mirror different degrees of alteration of tsTGF-beta1 signaling in different genetic aortic syndromes. PMID- 25113272 TI - If doctors can train part time, why not medical students? PMID- 25113271 TI - E pluribus unum, no more: from one crystal, many conformations. AB - Several distinct computational approaches have recently been implemented to represent conformational heterogeneity from X-ray crystallography datasets that are averaged in time and space. As these modeling methods mature, newly discovered alternative conformations are being used to derive functional protein mechanisms. Room temperature X-ray data collection is emerging as a key variable for sampling functionally relevant conformations also observed in solution studies. Although concerns about radiation damage are warranted with higher temperature data collection, 'diffract and destroy' strategies on X-ray free electron lasers may permit radiation damage-free data collection. X-ray crystallography need not be confined to 'static unique snapshots'; these experimental and computational advances are revealing how the many conformations populated within a single crystal are used in biological mechanisms. PMID- 25113273 TI - High density EEG-what do we have to lose? PMID- 25113274 TI - Upper limb function is normal in patients with restless legs syndrome (Willis Ekbom Disease). AB - OBJECTIVE: Restless legs syndrome, now called Willis-Ekbom Disease (RLS/WED), is a sensorimotor-related sleep disorder. Little is known of the effect of RLS/WED on motor function. The current study investigated upper limb function in RLS/WED patients. We hypothesised that RLS/WED patients exhibit subtle changes in tremor amplitude but normal dexterity and movement speed and rhythmicity compared to healthy controls. METHODS: RLS/WED patients (n=17, 59 +/- 7 years) with moderate disease and healthy controls (n=17, 58 +/- 6 years) completed screening tests and five tasks including object manipulation, maximal pinch grip, flexion and extension of the index finger (tremor assessment), maximal finger tapping (movement speed and rhythmicity assessment), and the grooved pegboard test. Force, acceleration, and/or first dorsal interosseus EMG were recorded during four of the tasks. RESULTS: Task performance did not differ between groups. Learning was evident on tasks with repeated trials and the magnitude of learning did not differ between groups. CONCLUSIONS: Hand function, tremor, and task learning were unaffected in RLS/WED patients. Patients manipulated objects in a normal manner and exhibited normal movement speed, rhythmicity, and tremor. SIGNIFICANCE: Further research is needed to assess other types of movement in RLS/WED patients to gain insight into the motor circuitry affected and the underlying pathophysiology. PMID- 25113277 TI - Left lower lobe torsion following upper lobectomy-prompt recognition and treatment improve survival. AB - Lobar torsion is a rare but life-threatening complication after lung resection. We report a case of left lower lobe torsion in 57-year-old women after upper lobectomy for underlying lung cancer. Definitive diagnosis of lung torsion was made at exploratory thoracotomy following abnormal chest radiography and bronchoscopy on the first post-operative day. An emergency completion pneumonectomy was performed and left lower lobe was resected. The post-operative course was uncomplicated and patient was discharged home on the seventh post operative day. Early recognition and prompt treatment of lobar torsion is essential for preventing potentially catastrophic complications including fatal gangrene of the pulmonary lobe. PMID- 25113276 TI - Imbalance of von Willebrand factor and its cleaving protease ADAMTS13 during systemic inflammation superimposed on advanced cirrhosis. AB - BACKGROUND & AIMS: Systemic inflammation in advanced cirrhosis represents a spectrum ranging from subclinical pathological bacterial translocation and immune activation to overt bacterial infection and sepsis. We hypothesized that systemic inflammation in cirrhosis is accompanied by a failure of ADAMTS13 to control the prothrombotic function of von Willebrand factor (VWF), which is increased in portal hypertension and hepatic fibrosis. METHODS: Patients with Child A cirrhosis (n = 25), Child B/C cirrhosis without clinical features of systemic inflammation (n = 31), and Child B/C cirrhosis with overt bacterial infections or systemic inflammatory response syndrome (n = 24) were analysed for ADAMTS13 and associated parameters and were followed to determine transplant-free survival. RESULTS: Plasma concentration and activity of ADAMTS13 were decreased in patients with systemic inflammation. Furthermore, ADAMTS13 inversely correlated with the extent of bacterial translocation and the severity of acute-phase reaction. As a function of reduced ADAMTS13 activity and increased VWF antigen, plasma from patients with superimposed inflammation strongly aggregated the platelet receptor glycoprotein Ib in presence of ristocetin. VWF:RCo correlated with higher concentrations of leucocytes and lipopolysaccharide-binding protein, organ dysfunction, augmented turnover of cross-linked intravascular fibrin, and the occurrence of acute kidney injury during follow-up. VWF:RCo of 390% or more predicted transplant-free survival in univariate analysis [HR = 8.24 (3.30 20.54)] and after adjustment for MELD [HR = 3.58 (1.30-9.88)]. However, adverse outcome was not associated with the accumulation of high-molecular weight VWF multimers. CONCLUSIONS: Systemic inflammation complicating advanced cirrhosis is accompanied by reduced activity of ADAMTS13 promoting a prothrombotic function of VWF, which can be employed to predict clinical outcome. PMID- 25113278 TI - Optimizing the electrical energy conversion cycle of dielectric elastomer generators. AB - A strategy to control the electrical charge is developed to achieve high energy density of soft dielectric elastomer generators for energy harvesting. The strategy is analytically shown and experimentally demonstrated to produce the highest energy density ever reported for a soft generator. PMID- 25113275 TI - Conditions for enhancing the encoding of an elementary motor memory by rTMS. AB - OBJECTIVE: Motor learning results in changes of movement representation in primary motor cortex (M1) a process involving long-term potentiation (LTP). Pairing motor training with repetitive transcranial magnetic stimulation (rTMS) of M1 enhances the formation of a motor memory. Here we determined the effect of pairing M1 stimulation and the execution of training movements at different times and frequencies on the formation of a motor memory. METHODS: Formation of a motor memory was defined as increases in motor evoked potentials (MEP) of the training agonist (extensor carpi ulnaris muscle, ECU) and increases in peak acceleration of the trained movements that last more than 60min. Training consisted of auditory-paced ballistic wrist extension movements (30min, 0.5Hz) paired with 0.1, 0.25 or 0.5Hz subthreshold rTMS. The rTMS pulse was applied at either the onset, 100ms prior to or 300ms after the onset of training movement related increases in electromyographic (EMG) activity of ECU. This was compared to a Sham condition. RESULTS: Only 0.1Hz rTMS applied at the onset of the training related increase in ECU-EMG activity resulted in increases in MEP amplitudes and peak acceleration when compared to the Sham. CONCLUSIONS: The formation of motor memory is enhanced above the naive level by co-administration of low frequency rTMS at the time of execution of training movements. SIGNIFICANCE: These results indicate the importance of time and frequency of rTMS in these settings and should be considered in the design of rehabilitation treatment strategies using rTMS. PMID- 25113280 TI - Elderly CML patients' treatment: considering not only physician's judgment but also co-morbidity indexes. PMID- 25113279 TI - Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection. AB - BACKGROUND: The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer owing to the negligible absorption and autofluorescence of water and other intrinsic biomolecules in this region. The main aim of the present study is to synthesize and characterize novel NIR fluorescent nanoparticles based on proteinoid and PLLA for early detection of colon tumors. METHODS: The present study describes the synthesis of new proteinoid-PLLA copolymer and the preparation of NIR fluorescent nanoparticles for use in diagnostic detection of colon cancer. These fluorescent nanoparticles were prepared by a self-assembly process in the presence of the NIR dye indocyanine green (ICG), a FDA-approved NIR fluorescent dye. Anti carcinoembryonic antigen antibody (anti-CEA), a specific tumor targeting ligand, was covalently conjugated to the P(EF-PLLA) nanoparticles through the surface carboxylate groups using the carbodiimide activation method. RESULTS AND DISCUSSION: The P(EF-PLLA) nanoparticles are stable in different conditions, no leakage of the encapsulated dye into PBS containing 4% HSA was detected. The encapsulation of the NIR fluorescent dye within the P(EF-PLLA) nanoparticles improves significantly the photostability of the dye. The fluorescent nanoparticles are non-toxic, and the biodistribution study in a mouse model showed they evacuate from the body over 24 h. Specific colon tumor detection in a chicken embryo model and a mouse model was demonstrated for anti-CEA-conjugated NIR fluorescent P(EF-PLLA) nanoparticles. CONCLUSIONS: The results of this study suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent P(EF-PLLA) nanoparticles over colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs such as paclitaxel and/or doxorubicin, within these biodegradable NIR fluorescent P(EF-PLLA) nanoparticles, for both detection and therapy of colon cancer. PMID- 25113281 TI - [Steppage gait in a 10 year-old girl]. PMID- 25113283 TI - Evaluating the implementation of a school-based emotional well-being programme: a cluster randomized controlled trial of Zippy's Friends for children in disadvantaged primary schools. AB - Schools are recognized as one of the most important settings for promoting social and emotional well-being among children and adolescents. This clustered randomized controlled trial evaluated Zippy's Friends, an international school based emotional well-being programme, with 766 children from designated disadvantaged schools. The purpose of this study was to evaluate the immediate and long term impact of the programme and to determine the impact of implementation fidelity on programme outcomes. Teachers reported emotional literacy outcomes using the Emotional Literacy Checklist, and emotional and behavioural outcomes using the Strengths and Difficulties Questionnaire. Controlling for the hierarchical structure of the data, path analysis using structural equation modelling revealed that the programme had a significant positive impact on the children's emotional literacy scores including significant improvements in the subscale scores of self-awareness (P < 0.001), self regulation (P < 0.01), motivation (P < 0.001) and social skills (P < 0.001) at post-intervention. These results were maintained at 12-month follow-up (P < 0.01). The programme, however, did not have a significant impact on children's emotional and behavioural problems. Analysis of programme fidelity indicated that high fidelity was directly related to improved emotional literacy scores at post intervention. PMID- 25113284 TI - Antifreeze effect of carboxylated epsilon-poly-L-lysine on the growth kinetics of ice crystals. AB - Some biological substances control the nucleation and growth of inorganic crystals. Antifreeze proteins, which prohibit ice crystal growth in living organisms, promise are also important as biological antifreezes for medical applications and in the frozen food industries. In this work, we investigated the crystallization of ice in the presence of a new cryoprotector, carboxylated epsilon-poly-L-lysine (COOH-PLL). In order to reveal the characteristics and the mechanism of its antifreeze effect, free-growth experiments of ice crystals were carried out in solutions with various COOH-PLL concentrations and degrees of supercooling, and the depression of the freezing point and growth rates of the tips of ice dendrites were obtained using optical microscopy. Hysteresis of growth rates and depression of the freezing point was revealed in the presence of COOH-PLL. The growth-inhibition effect of COOH-PLL molecules could be explained on the basis of the Gibbs-Thomson law and the use of Langmuir's adsorption isotherm. Theoretical kinetic curves for hysteresis calculated on the basis of Punin-Artamonova's model were in good agreement with experimental data. We conclude that adsorption of large biological molecules in the case of ice crystallization has a non-steady-state character and occurs more slowly than the process of embedding of crystal growth units. PMID- 25113286 TI - Self-compassion moderates the relationship between body mass index and both eating disorder pathology and body image flexibility. AB - The current study examined whether self-compassion, the tendency to treat oneself kindly during distress and disappointments, would attenuate the positive relationship between body mass index (BMI) and eating disorder pathology, and the negative relationship between BMI and body image flexibility. One-hundred and fifty-three female undergraduate students completed measures of self-compassion, self-esteem, eating disorder pathology, and body image flexibility, which refers to one's acceptance of negative body image experiences. Controlling for self esteem, hierarchical regressions revealed that self-compassion moderated the relationships between BMI and the criteria. Specifically, the positive relationship between BMI and eating disorder pathology and the negative relationship between BMI and body image flexibility were weaker the higher women's levels of self-compassion. Among young women, self-compassion may help to protect against the greater eating disturbances that coincide with a higher BMI, and may facilitate the positive body image experiences that tend to be lower the higher one's BMI. PMID- 25113287 TI - Body image and personality among British men: associations between the Big Five personality domains, drive for muscularity, and body appreciation. AB - The present study examined associations between the Big Five personality domains and measures of men's body image. A total of 509 men from the community in London, UK, completed measures of drive for muscularity, body appreciation, the Big Five domains, and subjective social status, and provided their demographic details. The results of a hierarchical regression showed that, once the effects of participant body mass index (BMI) and subjective social status had been accounted for, men's drive for muscularity was significantly predicted by Neuroticism (beta=.29). In addition, taking into account the effects of BMI and subjective social status, men's body appreciation was significantly predicted by Neuroticism (beta=-.35) and Extraversion (beta=.12). These findings highlight potential avenues for the development of intervention approaches based on the relationship between the Big Five personality traits and body image. PMID- 25113288 TI - Herpes PCR testing and empiric acyclovir use beyond the neonatal period. AB - BACKGROUND: Diagnostic strategies based on empirical testing and treatment to identify herpes simplex virus (HSV) infection in neonates may not be appropriate for older children in whom the most common presentation of severe infection is encephalitis, a rare and clinically recognizable condition. METHODS: Use of acyclovir in infants and children in 6 common non-HSV infection-related diagnosis related groups was characterized between 1999 and 2012 at 15 US pediatric hospitals by using the Pediatric Health Information System database. Characteristics of non-neonatal patients at 1 institution tested for HSV encephalitis over a 6.5-year period were then analyzed to identify factors associated with potentially unnecessary testing and treatment. RESULTS: Acyclovir use increased from 7.6% to 15.6% (P < .001) from 1999 to 2012. Much of this increase came in infants 30 to 60 days of age (82.7% increase, P < .001) and in patients with milder disease severity (44.8% increase, P < .001). Length of stay was increased by 2 days for children treated with acyclovir (P < .001). At our institution, 1394 HSV cerebrospinal fluid polymerase chain reactions were performed in children >30 days old, with only 3 positive results (0.22%). Comparison of the 3 subjects with positive testing and 55 with negative testing revealed that all cases, but only 4% (95% confidence interval 1.2%-14.0%) of noncases had clinical characteristics typical of HSV encephalitis. CONCLUSIONS: Strategies for diagnosis and empirical treatment of suspected HSV encephalitis beyond the neonatal period have trended toward the approach common for neonates without evidence of an increase in disease incidence. This may result in increased medical costs and risk to patients. PMID- 25113289 TI - Mild prematurity, proximal social processes, and development. AB - OBJECTIVE: To elucidate the role of gestational age in determining the risk of poor developmental outcomes among children born late preterm (34-36 weeks) and early term (37-38 weeks) versus full term (39-41 weeks) by examining the contribution of gestational age to these outcomes in the context of proximal social processes. METHODS: This was an analysis of the Canadian National Longitudinal Survey of Children and Youth. Developmental outcomes were examined at 2 to 3 (N= 15099) and 4 to 5 years (N= 12302). The sample included singletons, delivered at 34 to 41 weeks, whose respondents were their biological mothers. Multivariable modified Poisson regression was used to directly estimate adjusted relative risks (aRRs). We assessed the role of parenting by using moderation analyses. RESULTS: In unadjusted analyses, children born late preterm appeared to have greater risk for developmental delay (relative risk = 1.26; 95% confidence interval [CI], 1.01 to 1.56) versus full term. In adjusted analyses, results were nonsignificant at 2 to 3 years (late preterm aRR = 1.13; 95% CI, 0.90 to 1.42; early term aRR = 1.11; 95% CI, 0.96 to 1.27) and 4 to 5 years (late preterm aRR = 1.06; 95% CI, 0.79 to 1.43; early term aRR = 1.03; 95% CI, 0.85 to 1.25). Parenting did not modify the effect of gestational age but was a strong predictor of poor developmental outcomes. CONCLUSIONS: Our findings show that, closer to full term, social factors (not gestational age) may be the most important influences on development. PMID- 25113290 TI - Cognitive delay and behavior problems prior to school age. AB - OBJECTIVE: To investigate the relationship between cognitive delay (CD) and behavior problems between ages 9 months and 5 years, while adjusting for covariates related to CD. METHODS: Data were from 4 waves of the Early Childhood Longitudinal Study, Birth Cohort (n = 8000). Children were classified as typically developing (TD) or as having resolved, newly developed, or persistent CD between 9 and 24 months, based on scores from the Bayley Short Form-Research Edition below or above the 10th percentile. Child behavior was measured by using the Infant/Toddler Symptom Checklist (ages 9 and 24 months) and the Preschool and Kindergarten Behavior Scales (ages 4 and 5 years); children in the top 10th percentile were considered to have a behavior problem. Hierarchical linear modeling estimated the effect of CD status on children's behavioral trajectories, adjusted for confounders. RESULTS: CD resolved for 80.3% of children between 9 and 24 months. Behavior problems at 24 months were detected in 19.3%, 21.8%, and 35.5% of children with resolved, newly developed, and persistent CD, respectively, versus 13.0% of TD children. Behavior problems increased among children with CD over time, and more so among children with persistent CD. By age 5, children with persistent CD had behavior scores moderately (0.59 SD) higher than TD children. CONCLUSIONS: Behavior problems among children with CD are slightly higher at 9 months, clearly evident by 24 months, and increase as children move toward school age. Efforts to promote the earliest identification, evaluation, and service referral may be necessary to improve outcomes for these children. PMID- 25113291 TI - Variation in emergency department admission rates in US children's hospitals. AB - OBJECTIVE: To measure the hospital-level variation in admission rates for children receiving treatment of common pediatric illnesses across emergency departments (EDs) in US children's hospitals. METHODS: We performed a multi center cross sectional study of children presenting to the EDs of 35 pediatric tertiary-care hospitals participating in the Pediatric Health Information System (PHIS). Admission rates were calculated for visits occurring between January 1, 2009, and December 31, 2012, associated with 1 of 7 common conditions, and corrected to adjust for hospital-level severity of illness. Conditions were selected systematically based on frequency of visits and admission rates. RESULTS: A total of 1288706 ED encounters (13.8% of all encounters) were associated with 1 of the 7 conditions of interest. After adjusting for hospital level severity, the greatest variation in admission rates was observed for concussion (range 5%-72%), followed by pneumonia (19%-69%), and bronchiolitis (19%-65%). The least variation was found among patients presenting with seizures (7%-37%) and kidney and urinary tract infections (6%-37%). Although variability existed in disease-specific admission rates, certain hospitals had consistently higher, and others consistently lower, admission rates. CONCLUSIONS: We observed greater than threefold variation in severity-adjusted admission rates for common pediatric conditions across US children's hospitals. Although local practices and hospital-level factors may partly explain this variation, our findings highlight the need for greater focus on the standardization of decisions regarding admission. PMID- 25113292 TI - Impact locations and concussion outcomes in high school football player-to-player collisions. AB - BACKGROUND: Little research has examined concussion outcomes in terms of impact location (ie, the area on the head in which the impact occurred). This study describes the epidemiology of concussions resulting from player-to-player collision in high school football by impact location. METHODS: National High School Sports-Related Injury Surveillance Study data (2008/2009-2012/2013) were analyzed to calculate rates and describe circumstances of football concussion (eg, symptomology, symptom resolution time, return to play) resulting from player to-player collisions by impact location (ie, front-, back-, side-, and top-of-the head). RESULTS: Most concussions resulting from player-to-player collisions occurred from front-of-the-head (44.7%) and side-of-the-head (22.3%) impacts. Number of symptoms reported, prevalence of reported symptoms, symptom resolution time, and length of time to return to play were not associated with impact location. However, a larger proportion of football players sustaining concussions from top-of-the-head impacts experienced loss of consciousness (8.0%) than those sustaining concussions from impacts to other areas of the head (3.5%) (injury proportion ratio 2.3; 95% confidence interval 1.2-4.2; P = .008). Players had their head down at the time of impact in a higher proportion of concussions caused by top-of-the-head impacts (86.4%) than concussions from impacts to other areas of the head (24.0%) (injury proportion ratio 3.6; 95% confidence interval 3.2-4.0; P < .001). CONCLUSIONS: Among high school football players who sustained concussions due to player-to-player collisions, concussion outcomes were generally independent of impact location. Recommended strategies for reducing the proportion of top-of-the-head impacts include improved education regarding tackling with proper "head-up" technique. PMID- 25113293 TI - Reducing catheter-associated urinary tract infections: a quality-improvement initiative. AB - BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are among the most common health care-associated infections in the United States, yet little is known about the prevention and epidemiology of pediatric CAUTIs. METHODS: An observational study was conducted to assess the impact of a CAUTI quality improvement prevention bundle that included institution-wide standardization of and training on urinary catheter insertion and maintenance practices, daily review of catheter necessity, and rapid review of all CAUTIs. Poisson regression was used to determine the impact of the bundle on CAUTI rates. A retrospective cohort study was performed to describe the epidemiology of incident pediatric CAUTIs at a tertiary care children's hospital over a 3-year period (June 2009 to June 2012). RESULTS: Implementation of the CAUTI prevention bundle was associated with a 50% reduction in the mean monthly CAUTI rate (95% confidence interval: 1.28 to -0.12; P = .02) from 5.41 to 2.49 per 1000 catheter-days. The median monthly catheter utilization ratio remained unchanged; ~90% of patients had an indication for urinary catheterization. Forty-four patients experienced 57 CAUTIs over the study period. Most patients with CAUTIs were female (75%), received care in the pediatric or cardiac ICUs (70%), and had at least 1 complex chronic condition (98%). Nearly 90% of patients who developed a CAUTI had a recognized indication for initial catheter placement. CONCLUSIONS: CAUTI is a common pediatric health care-associated infection. Implementation of a prevention bundle can significantly reduce CAUTI rates in children. PMID- 25113294 TI - Neuroinvasive arboviral disease in the United States: 2003 to 2012. AB - OBJECTIVE: To describe the epidemiologic and clinical syndromes associated with pediatric neuroinvasive arboviral infections among children in the United States from 2003 through 2012. METHODS: We reviewed data reported by state health departments to ArboNET, the national arboviral surveillance system, for 2003 through 2012. Children (<18 years) with neuroinvasive arboviral infections (eg, meningitis, encephalitis, or acute flaccid paralysis) were included. Demographic, clinical syndrome, outcome, geographic, and temporal data were analyzed for all cases. RESULTS: During the study period, 1217 cases and 22 deaths due to pediatric neuroinvasive arboviral infection were reported from the 48 contiguous states. La Crosse virus (665 cases; 55%) and West Nile virus (505 cases; 41%) were the most common etiologies identified. Although less common, Eastern equine encephalitis virus (30 cases; 2%) resulted in 10 pediatric deaths. La Crosse virus primarily affected younger children, whereas West Nile virus was more common in older children and adolescents. West Nile virus disease cases occurred throughout the country, whereas La Crosse and the other arboviruses were more focally distributed. CONCLUSIONS: Neuroinvasive arboviral infections were an important cause of pediatric disease from 2003 through 2012. Differences in the epidemiology and clinical disease result from complex interactions among virus, vector, host, and the environment. Decreasing the morbidity and mortality from these agents depends on vector control, personal protection to reduce mosquito and tick bites, and blood donor screening. Effective surveillance is critical to inform clinicians and public health officials about the epidemiologic features of these diseases and to direct prevention efforts. PMID- 25113296 TI - Identifying very preterm children at educational risk using a school readiness framework. AB - OBJECTIVES: Children born very preterm (VPT) are at high risk of educational delay, yet few guidelines exist for the early identification of those at greatest risk. Using a school readiness framework, this study examined relations between preschool neurodevelopmental functioning and educational outcomes to age 9 years. METHODS: The sample consisted of a regional cohort of 110 VPT (<= 32 weeks' gestation) and 113 full-term children born during 1998-2000. At corrected age 4 years, children completed a multidisciplinary assessment of their health/motor development, socioemotional adjustment, core learning skills, language, and general cognition. At ages 6 and 9, children's literacy and numeracy skills were assessed using the Woodcock-Johnson III Tests of Achievement. RESULTS: Across all readiness domains, VPT children were at high risk of delay/impairment (odds ratios 2.5-3.5). Multiple problems were also more common (47% vs 16%). At follow up, almost two-thirds of VPT children were subject to significant educational delay in either literacy, numeracy or both compared with 29% to 31% of full-term children (odds ratios 3.4-4.4). The number of readiness domains affected at age 4 strongly predicted later educational risk, especially when multiple problems were present. Receiver operating characteristic analysis confirmed >= 2 readiness problems as the optimal threshold for identifying VPT children at educational risk. CONCLUSIONS: School readiness offers a promising framework for the early identification of VPT children at high educational risk. Findings support the utility of >= 2 affected readiness domains as an effective criterion for referral for educational surveillance and/or additional support during the transition to school. PMID- 25113297 TI - Children in hospitals before there were children's hospitals. PMID- 25113299 TI - Evidence-based standardization and ED admission rate variation in US children's hospitals. PMID- 25113298 TI - Defining and determining medical necessity in Medicaid managed care. AB - OBJECTIVES: In 2013, the American Academy of Pediatrics published a policy statement calling for pediatricians to be informed about the need for specific pediatric medical necessity language because children deserve "the intent embedded in Medicaid." This study aims to explore the definitions and determinations of medical necessity in Medicaid Managed Care (MMC), document the relevant language used throughout Medicaid, and investigate whether the federal standard of medical necessity for children is replicated in related state documents. METHODS: We conducted a desk review of state statutes, model MMC contracts, and 2 provider manuals per state, for 33 states with a full-risk MMC model. RESULTS: The federal "to correct and ameliorate" standard was replicated in 100% of state regulations, 72% of MMC model contracts (n = 13 of 18 MMC model contracts available online), and 54% of provider manuals (n = 30 of 56 available and sampled online). Only 9 states had an explicit "preventive" pediatric medical necessity standard in their state regulations that exemplified "the intent imbedded in Medicaid." CONCLUSIONS: The federal medical necessity standard for children is not replicated consistently within MMC programs from the state, to health plans, to network providers. Although the majority of the documents reviewed included the standard, the presence of the standard decreased by almost half between state-level and network-provider-level regulations. Having a single, explicitly defined pediatric medical necessity definition replicated at all levels of the health system would reduce confusion and increase the ability of pediatricians to apply the standard more uniformly. PMID- 25113300 TI - Tachypnea of infancy as the first sign of Sanfilippo syndrome. AB - This report describes the first known case of Mucopolysaccharidosis type IIIA presenting with respiratory symptoms and characteristic lung pathology. This case highlights under-recognized areas of systemic involvement and earlier modes of presentation in lysosomal storage disorders as well as the importance of investigating infants who have persistent tachypnea. PMID- 25113295 TI - Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder with pleiotropic effects. AB - Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of chronic kidney disease in children. The care of ARPKD patients has traditionally been the realm of pediatric nephrologists; however, the disease has multisystem effects, and a comprehensive care strategy often requires a multidisciplinary team. Most notably, ARPKD patients have congenital hepatic fibrosis, which can lead to portal hypertension, requiring close follow-up by pediatric gastroenterologists. In severely affected infants, the diagnosis is often first suspected by obstetricians detecting enlarged, echogenic kidneys and oligohydramnios on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Surgical considerations can include the possibility of nephrectomy to relieve mass effect, placement of dialysis access, and kidney and/or liver transplantation. Families of patients with ARPKD also face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. They may therefore interface with genetic counselors, geneticists, and reproductive endocrinologists. Children with ARPKD may also be at risk for neurocognitive dysfunction and may require neuropsychological referral. The care of patients and families affected by ARPKD is therefore a multidisciplinary effort, and the general pediatrician can play a central role in this complex web of care. In this review, we outline the spectrum of clinical manifestations of ARPKD and review genetics of the disease, clinical and genetic diagnosis, perinatal management, management of organ-specific complications, and future directions for disease monitoring and potential therapies. PMID- 25113301 TI - Subdural hemorrhages associated with antithrombotic therapy in infants with cerebral atrophy. AB - Low-molecular-weight heparins, such as enoxaparin, are often used to treat thrombosis in infants. We present 4 infants with diffuse brain injury who developed cerebral venous sinus thrombosis or deep vein thrombosis and were treated with enoxaparin. These infants subsequently developed subdural hemorrhages, and enoxaparin was stopped. In 3 cases, the subdural hemorrhages were found on routine surveillance brain MRI, and in 1 case imaging was urgently obtained because of focal seizures. Two patients needed urgent neurosurgical intervention, and all subdural hemorrhages improved or resolved on follow-up imaging. Each infant developed severe neurologic deficits, probably from the coexisting diffuse brain injury rather than from the subdural hemorrhages themselves. The risk of intracranial hemorrhage from enoxaparin may be accentuated in patients with diffuse brain injury, and careful consideration should be given before treatment in this population. PMID- 25113302 TI - Hospitalizations for severe lower respiratory tract infections. AB - BACKGROUND: Hospitalization for lower respiratory tract infections (LRTIs) among children have been well characterized. We characterized hospitalizations for severe LRTI among children. METHODS: We analyzed claims data from commercial and Medicaid insurance enrollees (MarketScan) ages 0 to 18 years from 2007 to 2011. LRTI hospitalizations were identified by the first 2 listed International Classification of Diseases, Ninth Revision discharge codes; those with ICU admission and/or receiving mechanical ventilation were defined as severe LRTI. Underlying conditions were determined from out- and inpatient discharge codes in the preceding year. We report insurance specific and combined rates that used both commercial and Medicaid rates and adjusted for age and insurance status. RESULTS: During 2007-2011, we identified 16797 and 12053 severe LRTI hospitalizations among commercial and Medicaid enrollees, respectively. The rates of severe LRTI hospitalizations per 100000 person-years were highest in children aged <1 year (commercial: 244; Medicaid: 372, respectively), and decreased with age. Among commercial enrollees, >= 1 condition increased the risk for severe LRTI (1 condition: adjusted relative risk, 2.68; 95% confidence interval, 2.58 2.78; 3 conditions: adjusted relative risk, 4.85; 95% confidence interval, 4.65 5.07) compared with children with no medical conditions. Using commercial/Medicaid combined rates, an estimated 31289 hospitalizations for severe LRTI occurred each year in children in the United States. CONCLUSIONS: Among children, the burden of hospitalization for severe LRTI is greatest among children aged <1 year. Children with underlying medical conditions are at greatest risk for severe LRTI hospitalization. PMID- 25113303 TI - Small geographic area variations in prescription drug use. AB - BACKGROUND: Despite the frequency of pediatric prescribing little is known about practice differences across small geographic regions and payer type (Medicaid and commercial). OBJECTIVE: The goal of this research was to quantify variation in prescription drug use among northern New England children. METHODS: Northern New England, all-payer administrative data (2007-2010) permitted study of prescriptions for 949 821 children ages 0 to 17 years (1.75 million person-years [PYs]; 54% Medicaid, 46% commercial). Age- and gender adjusted overall and drug group-specific prescription use was quantified according to payer type (Medicaid or commercial) and within payer type across 69 hospital service areas (HSAs). We measured prescription fills per PY (rate) and annual, mean percentage of the population with any drug group-specific fills (prevalence). RESULTS: Overall mean annual prescriptions per PY were 3.4 (commercial) and 5.5 (Medicaid). Generally, these payer type differences were smaller than HSA-level variation within payer type. HSA-level rates of attention-deficit/hyperactivity disorder drug use (5th 95th percentile) varied twofold in Medicaid and more than twofold in commercially insured children; HSA-level antidepressant use varied more than twofold within each payer type. Antacid use varied threefold across HSAs and was highest in infants where commercial use paradoxically exceeded Medicaid. Prevalence of drug use varied as much as rates across HSAs. CONCLUSIONS: Prescription use was higher among Medicaid-insured than commercially insured children. Regional variation generally exceeded payer type differences, especially for drugs used in situations of diagnostic and therapeutic uncertainty. Efforts should advance best pediatric prescribing discussions and shared decision-making. PMID- 25113305 TI - Characterization of a partial exon 9/intron 9 deletion in the coagulation factor XII gene (F12) detected in two Turkish families with hereditary angioedema and normal C1 inhibitor. PMID- 25113304 TI - The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. PMID- 25113306 TI - US lung cancer trends by histologic type. AB - BACKGROUND: Lung cancer incidence rates overall are declining in the United States. This study investigated the trends by histologic type and demographic characteristics. METHODS: Surveillance, Epidemiology, and End Results (SEER) program rates of microscopically confirmed lung cancer overall and squamous cell, small cell, adenocarcinoma, large cell, other, and unspecified carcinomas among US whites and blacks diagnosed from 1977 to 2010 and white non-Hispanics, Asian/Pacific Islanders, and white Hispanics diagnosed from 1992 to 2010 were analyzed by sex and age. RESULTS: Squamous and small cell carcinoma rates declined since the 1990s, although less rapidly among females than males. Adenocarcinoma rates decreased among males and only through 2005, after which they then rose during 2006 to 2010 among every racial/ethnic/sex group; rates for unspecified type declined. Male/female rate ratios declined among whites and blacks more than among other groups. Recent rates among young females were higher than among males for adenocarcinoma among all racial/ethnic groups and for other specified carcinomas among whites. CONCLUSIONS: US lung cancer trends vary by sex, histologic type, racial/ethnic group, and age, reflecting historical cigarette smoking rates, duration, cessation, cigarette composition, and exposure to other carcinogens. Substantial excesses among males have diminished and higher rates of adenocarcinoma among young females have emerged as rates among males declined more rapidly. The recognition of EGFR mutation and ALK rearrangements that occur primarily in adenocarcinomas are the primary basis for the molecular revolution that has transformed lung cancer diagnosis and treatment over the past decade, and these changes have affected recent type-specific trends. PMID- 25113307 TI - [Placebo analgesia and sleep]. AB - The placebo response is a psychobiological phenomenon for clinical benefits following the administration of an inert substance whatever its form. This phenomenon can be attributed to a wide range of neurobiological processes, such as expectations of relief, the Pavlovian conditioning and learning, emotional regulation, and reward mechanisms, which are themselves under the influence of processes that take place during sleep. The study of placebo analgesia in healthy from a placebo conditioning associated with analgesic suggestions has highlighted a relationship between sleep, expectations of relief and placebo analgesia: when the induction is persuasive before sleep, expectations of relief modulate placebo response the next morning and paradoxical sleep correlates negatively with both expectations and the placebo response. When the analgesic experience before sleep is less persuasive, expectations of relief are still present but no longer interact with placebo analgesia while paradoxical sleep no longer correlates with the analgesic placebo response. Sleep-processes especially during paradoxical sleep seem to influence the relationship between expectations of relief and placebo analgesia. In this review, we describe the relationship between sleep and placebo analgesia, the mechanisms involved in the placebo response (e.g., conditioning, learning, memory, reward) and their potential link with sleep that could make it a special time for the building placebo response. PMID- 25113309 TI - Physical and chemical stability of proflavine contrast agent solutions for early detection of oral cancer. AB - BACKGROUND AND PURPOSE: Proflavine hemisulfate solution is a fluorescence contrast agent to visualize cell nuclei using high-resolution optical imaging devices such as the high-resolution microendoscope. These devices provide real time imaging to distinguish between normal versus neoplastic tissue. These images could be helpful for early screening of oral cancer and its precursors and to determine accurate margins of malignant tissue for ablative surgery. Extemporaneous preparation of proflavine solution for these diagnostic procedures requires preparation in batches and long-term storage to improve compounding efficiency in the pharmacy. However, there is a paucity of long-term stability data for proflavine contrast solutions. METHODS: The physical and chemical stability of 0.01% (10 mg/100 ml) proflavine hemisulfate solutions prepared in sterile water was determined following storage at refrigeration (4-8C) and room temperature (23C). Concentrations of proflavine were measured at predetermined time points up to 12 months using a validated stability-indicating high performance liquid chromatography method. RESULTS: Proflavine solutions stored under refrigeration were physically and chemically stable for at least 12 months with concentrations ranging from 95% to 105% compared to initial concentration. However, in solutions stored at room temperature increased turbidity and particulates were observed in some of the tested vials at 9 months and 12 months with peak particle count reaching 17-fold increase compared to baseline. Solutions stored at room temperature were chemically stable up to six months (94 105%). CONCLUSION: Proflavine solutions at concentration of 0.01% were chemically and physically stable for at least 12 months under refrigeration. The solution was chemically stable for six months when stored at room temperature. We recommend long-term storage of proflavine solutions under refrigeration prior to diagnostic procedure. PMID- 25113310 TI - Removal of trace organic chemicals and performance of a novel hybrid ultrafiltration-osmotic membrane bioreactor. AB - A hybrid ultrafiltration-osmotic membrane bioreactor (UFO-MBR) was investigated for over 35 days for nutrient and trace organic chemical (TOrC) removal from municipal wastewater. The UFO-MBR system uses both ultrafiltration (UF) and forward osmosis (FO) membranes in parallel to simultaneously extract clean water from an activated sludge reactor for nonpotable (or environmental discharge) and potable reuse, respectively. In the FO stream, water is drawn by osmosis from activated sludge through an FO membrane into a draw solution (DS), which becomes diluted during the process. A reverse osmosis (RO) system is then used to reconcentrate the diluted DS and produce clean water suitable for direct potable reuse. The UF membrane extracts water, dissolved salts, and some nutrients from the system to prevent their accumulation in the activated sludge of the osmotic MBR. The UF permeate can be used for nonpotable reuse purposes (e.g., irrigation and toilet flushing). Results from UFO-MBR investigation illustrated that the chemical oxygen demand, total nitrogen, and total phosphorus removals were greater than 99%, 82%, and 99%, respectively. Twenty TOrCs were detected in the municipal wastewater that was used as feed to the UFO-MBR system. Among these 20 TOrCs, 15 were removed by the hybrid UFO-MBR system to below the detection limit. High FO membrane rejection was observed for all ionic and nonionic hydrophilic TOrCs and lower rejection was observed for nonionic hydrophobic TOrCs. With the exceptions of bisphenol A and DEET, all TOrCs that were detected in the DS were well rejected by the RO membrane. Overall, the UFO-MBR can operate sustainably and has the potential to be utilized for direct potable reuse applications. PMID- 25113311 TI - Confidence and impact on clinical decision-making and behaviour in the emergency department. AB - BACKGROUND: Clinical competency is underpinned by the self-confidence of nurses to act. Confidence may be critical to the understanding of how practice choices are made and not made by nurses in extended practice roles. The aim of this study was to explore how emergency nurses perceived (i) self-confidence in undertaking an extended practice role; and (ii) the factors associated with confidence within clinical practice. METHODS: A multicentred qualitative exploratory study. Fifty two participants were included in the study. Across three sites 36 (28 females, 8 males) face to face interviews and 16 non-participant observations (13 females, 3 males) were conducted. RESULTS: The study generated new knowledge about self confidence, self-efficacy and the role that contextual factors have in regulating behaviour. It shows that self-confidence is an important resource that sustains a nurse's ability to problem solve and to critically think in order to determine how best to act. CONCLUSIONS: The development of self-confidence is important if we are to promote effective clinical decision-making. Education programmes need to identify strategies that can promote and support the development of self confidence and resilience. PMID- 25113312 TI - Shortfalls in residents' transfer documentation: challenges for emergency department staff. AB - BACKGROUND: Increasing numbers of residents are transferred from aged care facilities to emergency departments. Frequently, residents arrive with inadequate documentation regarding their presenting complaint or medical history, making it difficult for emergency department staff to make decisions about care. METHODS: A retrospective review of emergency department records was undertaken for residents transferred from residential aged care facilities to two emergency departments in Melbourne, Victoria in 2012. RESULTS: 2880 resident transfers were included in the sample, of which 408 transfers were randomly selected for documentation review. Clinically important documentation was frequently absent including: the reason for transfer to the ED (n=197, 48.2%); baseline cognitive function (n=244, 59.7%); and vital signs at time of complaint (n=285, 69.9%). When the reason for transfer was absent, residents with an altered conscious state had more investigations and spent longer in the emergency department than when the reason for transfer was recorded. CONCLUSION: Inadequate documentation negatively impacted the resident's journey through the emergency department. There is evidence that inadequate documentation contributes to poor patient outcomes. To minimise the gaps in the transfer documentation regular staff development and quality assurance programs may be required in residential aged care facilities. PMID- 25113308 TI - Biology of advanced uveal melanoma and next steps for clinical therapeutics. AB - Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherapies are reviewed, and next steps in the development of clinical therapeutics are discussed. PMID- 25113313 TI - Remote community-based public health nursing during a disaster: an ethnographic case study in Japan. AB - BACKGROUND: The Great East Japan Earthquake that occurred on March 11, 2011 generated a tsunami that directly struck Japan. Public health nurses (PHNs) played important roles in this disaster response and community recovery. This research identified a PHN's experience in an affected area. METHODS: An ethnographic case study approach was used to obtain in-depth information regarding the experiences of one PHN, using semi-structured interviews, participant observation, and statistical documents. RESULTS: Six themes were identified and explored, including that the PHN undertook overwhelming responsibilities to protect the local residents, made several autonomous decisions, and had a strong sense of mission. These were based on the relationship-building that occurred with the local residents due to the geographical characteristics and her own preparations. CONCLUSIONS: The findings encourage PHNs to participate in simulations of disasters in preparation for major catastrophes and establish good collaborative efforts with residents by being a part of the community. PMID- 25113314 TI - Patient perceptions of emergency department fast track: a prospective pilot study comparing two models of care. AB - BACKGROUND: Emergency department (ED) fast track has been shown to improve patient flow for low complexity presentations.(1) The optimal model of care and service delivery for fast track patients has not been established. AIMS: The objective of this pilot study was to compare patient satisfaction using two models of ED fast track - one in a tertiary hospital emergency department staffed by doctors and the other in a nearby urban district hospital staffed by nurse practitioners. We also wanted to determine the proportion of fast track patients who would prefer to see a General Practitioner (GP) instead of presenting to the ED. This pilot study was the foundation for subsequent studies later conducted by Dinh et al.(2,3) METHODS: This was an observational study using a convenience sample of patients. Eligible fast track patients were asked to complete a standardised satisfaction survey. Presenting problems and waiting times of patients were collected using patient information systems. Primary outcome measure was satisfaction rating using a 5-point Likert scale. Secondary outcomes were surrogate satisfaction measures encompassing questions on likelihood of returning to ED. A multivariate analysis was performed to obtain odds ratio for higher satisfaction scores. RESULTS: In total, 353 patients were recruited: 212 patients in the doctor treated group (DR) and 141 were in the nurse practitioner treated group (NP). The two groups had similar baseline characteristics in terms of age, gender, referral source and waiting times. Overall, 320/353(86%) patients rated their care as either very good or excellent, with only 0.6% rating their care as poor. Satisfaction scores in the NP group were higher than those in the DR group (median score 4 vs. 3, p<0.01). A greater proportion of patients in the NP group reported that they would return to the ED for a similar problem (99% vs. 91% p<0.01). Overall, 175/353 (50%) of patients indicated that they would prefer to see a general practitioner for a similar problem if available nearby. These numbers were slightly lower in the NP group (43% vs. 53%, p=0.05). CONCLUSIONS: Most patients were satisfied with ED fast track, irrespective of model of care. Patient satisfaction was greater in the group of patients using the nurse practitioner model of care. Around half of the fast track patients would prefer to see a general practitioner for a similar problem if available nearby. PMID- 25113315 TI - Wildfire disasters: implications for rural nurses. AB - BACKGROUND: As natural disasters are increasing globally, nursing's role in responding to disasters is evolving. Disaster nursing has emerged as a specialty that focuses on the care of groups and communities during disaster response. The role of rural nurses in disasters is less well defined. METHODS: A review of peer reviewed literature combined with the International Council of Nurses framework of Disaster Nursing Competencies was conducted to understand the roles and functions of nurses in rural areas that experience disasters. The authors' findings from investigating the effects of four wildfires in rural Canadian communities are also discussed. RESULTS: Six major themes derived from our wildfire studies were generated within the context of nursing practice and are useful in the preparation of rural nurses involved in disaster management and recovery. This adds to the current literature which by and large has not addressed nursing in rural catastrophes. CONCLUSION: Well-prepared and educated rural nurses who combine theoretical knowledge with their understanding of a rural community potentially can reduce the impact of a disaster. Other nursing roles include mentoring nursing students in disaster preparation and assisting in initiatives to address community recovery in the aftermath of a disaster. PMID- 25113316 TI - Sudden onset Oculo-cardiac Reflex post-traumatic eye injury in PNG: a case study and discussion. AB - This case study examines the onset of traumatic OCR--Oculo-cardiac Reflex--in the remote southern highlands of PNG. The spontaneous occurrence of OCR post-trauma in the clinical setting leads to sudden onset bradycardia, nausea and hypotension, resulting in cardiovascular compromise and deteriorating clinical conditions. Initial recognition of the characteristics of OCR will prepare the clinician to deal with the sequence of events that arise post the reflex initiation. PMID- 25113317 TI - Versatile Cu(I)/Pd(0) dual catalysis for the synthesis of quaternary alpha allylated carbonyl compounds: development, mechanistic investigations and scope. AB - We report herein a versatile cooperative dual catalysis reaction based on a Cu(I)/Pd(0) system. Mechanistic investigation shows that every component plays a crucial role in determining the reaction outcome. The reaction is successfully extended to various substrates; such as alpha,beta-unsaturated ketones, malonates and coumarins. The strategy tolerates different substitution patterns and affords good yields for each family of substrates. PMID- 25113318 TI - Time trends of antidepressant drug prescriptions in men versus women in a geographically defined US population. AB - The aim of this work was to study time trends of antidepressant drug (AD) prescriptions in a geographically defined US population between 2005 and 2011 for men and women separately. Using the Rochester Epidemiology Project medical records-linkage system, we identified all Olmsted County, MN residents who received AD outpatient prescriptions between 2005 and 2011 (7 years). We calculated the annual age- and sex-specific prevalence over 7 years and used generalized estimating equation models to test for time trends. The prevalence of subjects receiving at least one AD prescription was approximately two times higher in women than in men consistently across the 7 years of the study. The standardized annual prevalence increased from 10.8 % in 2005 to 14.4 % in 2011 overall, from 7.0 % in 2005 to 9.9 % in 2011 for men, and from 14.4 % in 2005 to 18.6 % in 2011 for women. The absolute percent increase was greater in women (4.2 vs. 2.9 %; standardized); however, the relative percent increase was greater in men (41.4 vs. 29.2 %; standardized). The relative percent increase was greater in the age group 65+ years for both men and women. AD prescriptions are increasing over time, especially in the elderly. Women receive more AD prescriptions than men. However, the relative increase in AD prescriptions over time is greater in men than women. PMID- 25113319 TI - Oral contraceptive use and psychiatric disorders in a nationally representative sample of women. AB - The purpose of this study is to examine the association between oral contraceptive use (any current use, duration, and type) and major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) in a nationally representative sample of women in the USA. Data were drawn from 1,105 women aged 20-39 in the National Health and Nutrition Examination Surveys from 1999 to 2004. The associations between self-reported use of oral contraceptives in the past year and DSM-IV diagnosed and subthreshold MDD, GAD, and PD in the past year were assessed comparing oral contraceptive users to all non-users, former users, and former long-term users. Women using oral contraceptives had a lower past-year prevalence of all disorders assessed, other than subthreshold MDD. When adjusted for confounders, women using oral contraceptives in the past year had significantly lower odds of subthreshold PD, compared to former users (odds ratio (OR) = 0.34, 95 % CI 0.14-0.84). Effects estimates were strongest for monophasic (versus multiphasic) oral contraceptive users. Hormonal contraceptive use was associated with reduced risk of subthreshold PD. A potential mental health benefit of hormonal contraceptives has substantial public health implications; prospective longitudinal studies are needed to confirm whether hormonal contraceptive use improves mental health. PMID- 25113320 TI - Providing care to a child with cancer: a longitudinal study on the course, predictors, and impact of caregiving stress during the first year after diagnosis. AB - OBJECTIVE: This study investigated the course, predictors, and impact of caregiving stress on the functioning of primary caregivers of children with cancer during the first year after a child's cancer diagnosis. METHODS: Primary caregivers (N = 95, 100% mother, 86% response rate) of consecutive newly diagnosed paediatric cancer patients (0-18 years) completed measures of caregiving stress, depressive symptoms, anxiety, and self-reported health at diagnosis, and 3, 6, and 12 months thereafter. RESULTS: Results indicated a significant decrease in caregiving stress (especially during the first 3 months after diagnosis). Caregiving stress was predicted by single marital status and the ill child being the mother's only child. Multilevel analyses, controlled for socio-demographic and medical covariates, showed that, over time, the decline in caregiving stress was accompanied by a reduction in depressive symptoms and anxiety. The amount of variance explained by caregiving stress was 53% for depressive symptoms, 47% for anxiety, and 3% for self-reported health. CONCLUSIONS: The present study suggests that caregiving stress is an important factor in understanding parental adjustment to childhood cancer. This offers possibilities for developing interventions aimed at preventing caregiving stress, and strengthening mothers' confidence in their ability to provide good care. PMID- 25113322 TI - One pot synthesis of nanoscale phase-segregated PdPt nanoarchitectures via unusual Pt-doping induced structural reorganization of a Pd nanosheet into a PdPt nanotent. AB - Pt-doping of an ultrathin Pd nanosheet results in the unprecedented structural rearrangement of a Pd nanosheet into a PdPt nanotent structure, in which a tripod stands on a triangular nanosheet. Further growth of Pt phase on this nanotent structure is dependent on the presence of surface-stabilizing CO molecules, leading to the formation of two distinct nanoscale phase segregated structures with respective structural features of a popped out Pt facet and an overgrown Pt layer. PMID- 25113324 TI - [Prurigo nodularis: A puzzle for more than 100 years]. PMID- 25113325 TI - [Nihil certum: historical development of the term prurigo]. AB - The term prurigo is still used to designate primary dermatoses and secondary reaction patterns. A clear definition of the term is not available nor a clear clinical classification of diseases categorized under the term. Furthermore, there is no certainty about the entity it was primarily used to refer to, and whether it should always be considered in relation to pruritus. The concept appears already in very early medical treatises. From the very beginning, it was used in dermatology in a non-uniform way, and was alternately accorded and denied the status of an independent disease entity. Moreover, prurigo was subdivided into many different forms, but their descriptions are partly very similar, so that, for instance, it is quite difficult today to draw any conclusions about the clinical entities the frequently used terms prurigo mitis and prurigo formicans referred to. In contrast, the term prurigo nodularis is still commonly used. This article traces exemplarily the use of the term prurigo in the standard medical textbooks up to the definition of prurigo nodularis. PMID- 25113326 TI - [Prurigo. Clinical definition and classification]. AB - BACKGROUND: There is no consistent definition of the term prurigo and a clear classification is unavailable. OBJECTIVES: Definition of the current forms of prurigo and a new approach to a specific classification. METHODS: Review of the types of prurigo as presented in current textbooks and publications. RESULTS: Pruritus is the main symptom of prurigo and shows an intensely pruritic papule or nodule as the main efflorescence. The term prurigo is not only used for secondary lesions, but also for primary dermatoses. The different forms of prurigo obtain their names depending on etiology, onset and duration of lesions or the clinical appearance. CONCLUSIONS: The term prurigo has not been used consistently. A revision of the classification with a clear distinction between primary dermatoses and secondary lesions seems reasonable. In secondary prurigo, a clinical classification and the cause should be mentioned. PMID- 25113321 TI - Comparing algorithms for automated vessel segmentation in computed tomography scans of the lung: the VESSEL12 study. AB - The VESSEL12 (VESsel SEgmentation in the Lung) challenge objectively compares the performance of different algorithms to identify vessels in thoracic computed tomography (CT) scans. Vessel segmentation is fundamental in computer aided processing of data generated by 3D imaging modalities. As manual vessel segmentation is prohibitively time consuming, any real world application requires some form of automation. Several approaches exist for automated vessel segmentation, but judging their relative merits is difficult due to a lack of standardized evaluation. We present an annotated reference dataset containing 20 CT scans and propose nine categories to perform a comprehensive evaluation of vessel segmentation algorithms from both academia and industry. Twenty algorithms participated in the VESSEL12 challenge, held at International Symposium on Biomedical Imaging (ISBI) 2012. All results have been published at the VESSEL12 website http://vessel12.grand-challenge.org. The challenge remains ongoing and open to new participants. Our three contributions are: (1) an annotated reference dataset available online for evaluation of new algorithms; (2) a quantitative scoring system for objective comparison of algorithms; and (3) performance analysis of the strengths and weaknesses of the various vessel segmentation methods in the presence of various lung diseases. PMID- 25113327 TI - [Pathogenesis of prurigo nodularis]. AB - BACKGROUND: Prurigo nodularis is a chronic reaction pattern associated with severe pruritus that markedly affects the quality of life in patients. PATHOGENESIS: The pathogenesis of prurigo nodularis is not completely clear. Patients have an increased number of substance P and calcitonin gene-related peptide positive nerves in the dermis. Eosinophils and mast cells are in close vicinity to peripheral nerves and increased in numbers in the inflammatory infiltrate in prurigo nodularis. Nerve growth factor (NGF) is increased in lesional skin of patients and can be released by mast cells and eosinophils. In addition, NGF modulates the functional activity of mast cells and eosinophils. Recently, higher levels of the novel pruritic cytokine IL-31 were found in the skin of patients with prurigo nodularis than other pruritic skin diseases. CONCLUSION: The pathogenesis of prurigo nodularis seems to be regulated by immunological and neuronal plasticity which will be highlighted in the current article. PMID- 25113328 TI - [Prurigo nodularis: its association with dermatoses and systemic disorders]. AB - BACKGROUND: Prurigo is seen in various dermatological diseases, but also in systemic and neurological diseases. OBJECTIVES: Which diseases in dermatology, internal medicine and neurology are linked to prurigo nodularis? MATERIAL AND METHODS: We describe the various entities that are associated with prurigo and discuss pathogenetic and therapeutic implications. RESULTS: In dermatology prurigo nodularis is most frequently seen in atopic dermatitis, but also in cutaneous lymphomas, mycobacterial skin infections and bullous diseases. Among systemic diseases, prurigo nodularis frequently is associated with pruritus of chronic renal or hepatic diseases. Prurigo nodularis is also seen in hematological and metabolic diseases (such as solid tumors, lymphoma, diabetes mellitus). The pathophysiology of prurigo is only partly understood. Treatment of prurigo nodularis is often challenging and a multimodal approach is advisable. CONCLUSION: Prurigo nodularis is a skin manifestation of chronic pruritus caused by various diseases in dermatology, internal medicine and neurology. An interdisciplinary approach should be taken for diagnosis and therapy. PMID- 25113329 TI - [Psychosomatic aspects of prurigo nodularis]. AB - BACKGROUND/OBJECTIVES: This article gives an overview of the theoretical background and the empirical research concerning psychosomatic aspects of prurigo nodularis (PN). MATERIALS AND METHODS: Literature research in PubMed with the search terms "prurigo nodularis", "nodular prurigo", "psych*"; clinical experience and research of the authors. RESULTS: Although reviews on PN frequently mention psychosomatic aspects, there is little empirical research concerning the subject. Psychosomatic aspects of PN may play a role in (1) the etiology of the chronic pruritus; (2) scratching, which leads to the typical nodules of PN; (3) the consequences of the chronic pruritus, the scratching and the skin lesions; (4) comorbidity. There is evidence for higher psychic comorbidity and higher psychopathology (anxiety, depression) in PN patients than in healthy controls, but PN patients were comparable to patients with other pruritic dermatoses. DISCUSSION: Increased levels of psychopathological problems and comorbidities also have been found in other dermatoses; they are not specific for PN. Because all of the research on this topic is cross-sectional, we cannot be sure whether these aspects are etiological factors or consequences of PN or independent comorbidities. Nevertheless, psychosomatic aspects should be considered in diagnosis and treatment of PN patients. PMID- 25113330 TI - [Therapy of prurigo nodularis]. AB - Treatment of prurigo nodularis is a challenge. No specific therapies are approved and data from clinical trials are rare. Based on our experience, case series, randomized controlled trials as well as the S2k guideline on chronic pruritus, we provide general principles and specific recommendations in this review. PMID- 25113332 TI - [Reticulate necrotic lesions on lower legs]. PMID- 25113333 TI - [Acne vulgaris]. AB - Acne vulgaris is worldwide the most common skin disease. Acne is an inflammatory disorder in whose emergence androgens, PPAR ligands, the IGF-1 signaling pathway, regulating neuropeptides and environmental factors are probably involved. These factors interrupt the natural cycling process in the sebaceous gland follicle and support the transition of microcomedones to comedones and inflammatory lesions. Proinflammatory lipids and cytokines are mediators for the development of acne lesions. Bacterial antigens can potentate the inflammatory phenomena. Acne is predominantly treated with combination therapy. Selecting a treatment regimen depends on the exact classification of acne type and severity. The development of scars is the main criterion for the choice of systemic therapy. Retinoids for mild comedonal acne and the combination of retinoids with antibiotics and/or benzoyl peroxide for mild to moderate papulopustular acne are the drugs of first choice for topical treatment. The use of topical antibiotics is not recommended any more because of the development of resistant bacterial strains. Systemic antibiotics, in combination with topical retinoids and/or benzoyl peroxide, for moderate papular/nodular acne and isotretinoin for severe nodular/conglobate acne are the columns of systemic acne treatment. Systemic anti-androgens are used in women against moderate papulopustular acne. Due to advances in the understanding of the underlying inflammatory mechanisms in recent years the development of new therapeutic agents with good efficacy and better side effect profile should be expected in the future. PMID- 25113331 TI - [Clinical features and prurigo nodularis in nephrogenic pruritus]. AB - BACKGROUND: Nephrogenic pruritus (NP) is a well-known associated symptom in patients with chronic renal failure. The aim of the present study was to make a detailed dermatological analysis including distribution of excoriations and their correlation with pruritus characteristics. PATIENTS AND METHODS: Data on a total of 17 patients with NP (14 males, mean 65.4 +/- SD 14.3 years) were subjected to retrospective analysis. Most of the patients developed NP after start of kidney disease; however, in 20 % of the patients, there was premonitory appearance of the symptom 18 months (median) earlier. A majority of patients reported neuropathic symptom qualities (burning, stinging). In 94.1 % of patients xerosis was present; in 58.8 %, prurigo nodularis. The latter group of patients had a longer duration of pruritus as well as up to 10 years longer duration of renal disease than those without prurigo. RESULTS: Pruritus characteristics of NP show a wide variance without a clear profile that is useful for clinical diagnosis. NP can occur premonitorily, and, if of long duration and with coexistent metabolic diseases, can develop into prurigo. PMID- 25113334 TI - Revision of the neotropical jumping plant-louse genus Mastigimas (Hemiptera, Psylloidea) attacking Cedrela and Toona species (Meliaceae). AB - The small Neotropical genus Mastigimas with five described species is revised. Three new species are added: Mastigimas colombianus sp. n. from Colombia on Cedrela montana, M. drepanodis sp. n. from Brazil (Parana) on C. fissilis and M. reseri sp. n. from Jamaica collected in light traps. Another two species are recorded from Brazil and Colombia, respectively, which are not formally described due to insufficient material. The new species are described, and illustrations and identification keys are provided for all species. The last instar immatures are described for five species. The phylogeny within Mastigimas is analysed, and the biogeographic and host plant relationships are discussed. PMID- 25113335 TI - Mature larva of Stenichnus collaris (Muller & Kunze) (Coleoptera: Staphylinidae: Scydmaeninae). AB - The mature larva of Stenichnus collaris is re-described on the basis of a shed larval skin. This is the first description of an immature Stenichnus identified by rearing to an adult beetle, and not only by collecting the larva in association with adults, as in previously published works. New data on the life history of St. collaris are provided, and possible serial homology of chaetotaxic structures across body segments is discussed. The structures of immature Nearctic St. turbatus, the only Stenichnus larva described with focus on the chaetotaxy, are compared with those of St. collaris and possible homologies are indicated. PMID- 25113336 TI - Morphological variation and affinities of the poorly known snake Atractus caxiuana (Serpentes: Dipsadidae) . AB - Atractus caxiuana was recently described based on three specimens (two males and one female) from the Floresta Nacional de Caxiuana, municipality of Melgaco, state of Para, in the eastern portion of the Brazilian Amazon. Apart from the type series, no additional samples are known for the species. In this study, we report new specimens of A. caxiuana, providing new morphological data (meristic, morphometric, pholidosis, colour pattern, and hemipenis) and localities. We relate the variability displayed by the characters analyzed to sexual dimorphism, geographic variation, and ontogeny. Additionally, we provide detailed comparisons with A. collaris and putative sister species, and propose a new species group to accommodate this distinct and possible monophyletic assemblage. PMID- 25113337 TI - Description of a new genus, Chileana (Hymenoptera: Chalcidoidea: Torymidae), with four new species. AB - Chileana Jansta & Krizkova gen. nov. and four new species, C. cyanea Jansta & Krizkova sp. nov., C. maculata Jansta & Krizkova sp. nov., C. tricarinata Jansta & Krizkova sp. nov. and C. penai Jansta & Krizkova sp. nov., all from Chile, are described. The placement of this new genus within the tribe Monodontomerini is discussed and several characters suggest a close relationship to Zaglyptonotus. PMID- 25113338 TI - Redescription of three species of Filistatidae (Araneae) described by C.F. Roewer from Afghanistan. AB - Types of three filistatid species described by Roewer (1960, 1962) from Afghanistan are redescribed and two of them transferred to other filistatid genera. The new combinations proposed are: Zaitunia afghana (Roewer 1962) comb. n. (ex. Filistata Latreille, 1810) and Tricalamus lindbergi (Roewer, 1962) comb. n. (ex. Pritha Lehtinen, 1967). The taxonomic position of Pholcoides afghana Roewer, 1960 is discussed and the species is placed in the filistatid subfamily Prithinae Gray, 1994. PMID- 25113339 TI - A new Philautus (Anura: Rhacophoridae) from northern Laos allied to P. abditus Inger, Orlov & Darevsky, 1999. AB - The small rhacophorid frog Philautus abditus is geographically restricted to central Vietnam and adjacent Cambodia. Our fieldwork in northern Laos resulted in the discovery of a Philautus species that very closely resembles P. abditus, but is at least 330 km from the nearest known locality of that species. The Laos population differs from P. abditus in mitochondrial DNA and coloration, and is described here as a new species. Philautus nianeae sp. nov. is distinguished from its congeners by having the combination of a hidden tympanum; no nuptial pads; smooth skin; large black spots on the hidden surfaces of the hind limbs; light venter with dark spotting; and a bronze iris. A second species of Philautus from northern Laos, P. petilus, is transferred on the basis of morphology to the genus Theloderma. PMID- 25113340 TI - Discovery of the female of Protohermes niger Yang & Yang (Megaloptera: Corydalidae): Sexual dimorphism in coloration of a dobsonfly revealed by molecular evidence. AB - In most species of Megaloptera, adult males and females have similar coloration. In this paper, we associate the adult female of a Chinese endemic dobsonfly species, Protohermes niger Yang & Yang, using molecular evidence from two mitochondrial genes (16S rRNA and COI). The body and wing coloration between the male and the female of P. niger exhibits distinct sexual dimorphism. PMID- 25113341 TI - New contributions to the knowledge of the immatures of Stilobezzia punctulata Lane and Stilobezzia fiebrigi Kieffer (Diptera: Ceratopogonidae). AB - The fourth instar larva of Stilobezzia punctulata Lane is described for the first time and the one of Stilobezzia fiebrigi Kieffer is redescribed. They are illustrated and photomicrographed from material collected in different aquatic environments of the province of Corrientes, Argentina. Both species show features typical to carnivorous-predatory larva. PMID- 25113342 TI - Neojilinga, a replacement name for Jilinga Eitschberger, Danner & Surholt, 1998 (Lepidoptera: Sphingidae). PMID- 25113343 TI - Bees of the Colletes clypearis-group (Hymenoptera: Apoidea: Colletidae) from China with descriptions of seven new species. AB - Twenty-three known species of the Colletes clypearis speices group from China are treated in this paper. C. cinerascens Morawitz 1893, C. clypearis Morawitz 1876, C. floralis Eversmann 1852, C. impunctatus Nylander 1852, Colletes paratibeticus Kuhlmann 2002 and Colletes sodalis (Cameron 1897) are newly recorded from China. C. harrerioides sp. n., C. heilongtenensis sp. n., C. hirsutus sp. n., C. inspersus sp. n., C. xizangensis sp. n., C. xuezhongi sp. n. and C. yanruae sp. n. are described and illustrated as new species. Checklist of the known species from China in Colletes clypearis-group with distribution, floral records, and an illustrated key to all known males and females from China are provided. The type specimens of the new species are deposited in the Insect Collection of Institute of Zoology, Chinese Academy of Sciences, Beijing, China. PMID- 25113344 TI - Taxonomic review of the family Discodorididae (Mollusca: Gastropoda: Nudibranchia) from Brazil, with descriptions of two new species. AB - The family Discodorididae was previously represented by 11 species in Brazil; however, recently collected specimens from several localities in Rio de Janeiro, in addition to the study of material previously deposited in scientific collections, revealed the existence of 13 taxa: Diaulula greeleyi (MacFarland, 1909), Discodoris hummelincki (Ev. Marcus & Er. Marcus, 1963) comb. nov., Discodoris branneri MacFarland, 1909, Geitodoris pusae (Er. Marcus, 1955), Hoplodoris hansrosaorum Dominguez, Garcia & Troncoso, 2006, Jorunna spazzola Er. Marcus, 1955, Jorunna spongiosa sp. nov., Paradoris mulciber (Ev. Marcus, 1971), Platydoris angustipes (Morch, 1863), Rostanga byga Er. Marcus, 1958a, Taringa telopia Er. Marcus, 1955, Taringa iemanja sp. nov., and Thordisa diuda Er. Marcus, 1955. Discodoris voniheringi MacFarland, 1909 was previously regarded as nomen dubium, and this view is maintained in the present study. Three new records for the Brazilian coast are recognized among these 13 taxa; the previous record of Diaulula phoca (Ev. Marcus & Er. Marcus, 1967a) is rectified as Discodoris hummelincki comb. nov., constituting the first record of this species from Brazil; two new species, Taringa iemanja sp. nov. and Jorunna spongiosa sp. nov., are described in anatomical detail. The following taxa, which were formerly considered junior synonyms of species studied in this work, have been revalidated: Diaulula nayarita (Ortea & Llera, 1981), from the Pacific coast of Costa Rica, which differs from Diaulula greeleyi in the length and width of caryophyllidia; Discodoris mortenseni Ev. Marcus & Er. Marcus, 1963, from the Caribbean, which is likely to belong to Jorunna, yet differs from Jorunna spazzola in body size and coloration, radula appearance, and number of lamellae in the rhinophores; Jorunna luisae Ev. Marcus, 1976, which differs from Jorunna spazzola in the reproductive system, mainly in the size and shape of the accessory gland; and Thordisa azmani Cervera & Garcia-Gomez, 1989, which differs from Thordisa diuda in the presence of two accessory glands in the genital atrium and the absence of one denticle in the external surface of the inner lateral teeth. Finally, the specimens of Geitodoris pusae reported from the European coast and Mediterranean Sea show differences in general coloration and in the radula, gill, and reproductive system, thereby these specimens likely refer to different taxa. PMID- 25113345 TI - World synopsis of described species of the genus Platypygus Loew (Diptera: Mythicomyiidae: Platypyginae). AB - The taxonomy of the genus Platypygus Loew is summarized, previously described species are reviewed based on examination of types, and a key to known species of the genus worldwide is presented. All previously described species are diagnosed and illustrated. The male genitalia of P. ridibundus (Costa) and female genitalia of P. americanus Melander are described for the first time. Some characters supporting the monophyly of the genus Platypygus are discussed and the Nearctic Cyrtisiopsis americanus (Melander) is restored to its original combination as Platypygus americanus. The type status of Platypygus bellus Loew, P. lativentris Loew, P. pumilio Loew, and P. turkmenorum Paramonov is clarified and a lectotype is selected for Platypygus kurdorum Paramonov and P. tauricus Paramonov. New country records are given for the following species: P. bellus (Greece); P. chrysanthemi (Israel, Jordan); P. kurdorum (Israel, Jordan, Syria); P. limatus (Nepal, Thailand); P. pumilio (Greece, Turkmenistan); P. ridibundus (Cyprus, Israel, Portugal), P. titanomedea (Jordan, Turkey). PMID- 25113346 TI - Description of Culicoides paradoxalis sp. nov. from France and Portugal (Diptera: Ceratopogonidae). AB - A new species, Culicoides paradoxalis Ramilo and Delecolle (Diptera: Ceratopogonidae), is described from specimens collected in France (Corsica and southeast region) and Portugal. This species resembles Culicoides lupicaris Downes and Kettle, and can be distinguished from this species and from Culicoides newsteadi Austen by its wing pattern, in addition to the absence of spines on the tarsomere 4 of female mid leg. In male, the presence of two appendices on the sternite 9 together with the absence of sensilla coeloconica on the flagellomere 11 is also useful to distinguish these three species. Separation from other members of the Culicoides subgenus is confirmed by the analysis of the Cytochrome Oxidase I (COI) mitochondrial marker. PMID- 25113347 TI - Two new species of scale mites (Acari: Pterygosomatidae) parasitizing Agama agama (Sauria: Agamidae) from Kenya. AB - Two new species of pterygosomatid mites Pterygosoma garissi sp. nov. and P. fragilis sp. nov. (Acari: Pterygosomatidae) are described from the agamid lizard Agama agama (Sauria: Agamidae) from Kenya. P. garissi sp. nov. is similar to P. annectans Jack, 1962 but in the new species the peripheral setae are slightly expanded apically, 3 pairs of setae are situated on the coxal fields I and and 2 pairs on II coxal fields, all pseudoanal setae are paddle-shaped with minute spicules on the apical part, setae dFIV are absent and lTrIV present. P. fragilis sp. nov. is most closely related to P. garissi sp. nov. but differs by the presence of setae n on the subcapitulum, the hypostome with several denticles at the apex, the fixed cheliceral digit bearing a spinous process, the presence of 8 9 pairs of the peripheral setae, 1-2 pairs of genital setae g, and by the cheliceral shaft 2.1 times longer than the cheliceral base. PMID- 25113348 TI - Two new endemic species of Ameiva (Squamata: Teiidae) from the dry forest of northwestern Peru and additional information on Ameiva concolor Ruthven, 1924. AB - We describe two new species of Ameiva Meyer, 1795 from the dry forest of the Northern Peruvian Andes. The new species Ameiva nodam sp. nov. and Ameiva aggerecusans sp. nov. share a divided frontal plate and are differentiated from each other and from their congeners based on genetic (12S and 16S rRNA genes) and morphological characteristics. A. nodam sp. nov. has dilated postbrachials, a maximum known snout-vent length of 101 mm, 10 longitudinal rows of ventral plates, 86-113 midbody granules, 25-35 lamellae under the fourth toe, and a color pattern with 5 longitudinal yellow stripes on the dorsum. Ameiva aggerecusans sp. nov. has not or only hardly dilated postbrachials, a maximum known snout-vent length of 99.3 mm, 10-12 longitudinal rows of ventral plates, 73-92 midbody granules, 31-39 lamellae under the fourth toe, and the females and juveniles of the species normally exhibit a cream-colored vertebral stripe on a dark dorsum ground color. We provide information on the intraspecific variation and distribution of A. concolor. Furthermore, we provide information on the environmental niches of the taxa and test for niche conservatism. PMID- 25113349 TI - Polymona schellhorni sp nov., a new lymantrid moth from Jordania (Lepidoptera: Lymantriidae). PMID- 25113351 TI - The Australian Byrrhinae (Coleoptera: Byrrhidae) with descriptions of new genera and species. AB - The generic classification of the Australian Byrrhinae is revised and the following new genera are described: Notolioon gen. n., Nothochaetes gen. n., Idiothrix gen. n., Akidomorychus gen. n., Brachybyrrhulus gen. n. and Pseudomorychus gen. n. A key is provided for the genera of Australian Byrrhidae. The following new combinations are proposed: Notolioon atronitens (Lea 1920) comb. n., N. bryophagus (Lea 1907) comb. n., N. carissimus (Lea 1907). comb. n., N. dives (Lea 1907) comb. n., N. gemmatus (Lea 1920) comb. n., N. globosus (Wilson 1921) comb. n., N. griffithi (Lea 1907) comb. n., N. maculatipes (Lea 1920) comb. n., N. multicolor (Lea 1907) comb. n., N. nodipennis (Lea 1920) comb. n., N. simplicicornis (Lea 1907) comb. n., N. viridinitens (Lea (1920). comb. n., Nothochaetes fasciculatus (Lea 1920) comb. n., Idiothrix carinaticeps (Lea 1920) comb. n., Akidomorychus comatus (Oke 1932) comb. n., A. polychromus (Lea 1920) comb. n., A. raucus (Blackburn 1891) comb. n., A. venustus (Wilson 1921) comb. n., Brachybyrrhulus discicollis (Lea 1920) comb. n., Pseudomorychus torrensensis (Blackburn 1889) comb. n., P. mixtus (Lea 1907) comb. n. The following new species are described: Notolioon cardamine sp. n., Nothochaetes howensis sp. n. and Brachybyrrhulus malleecola sp. n. PMID- 25113352 TI - On the endemic spider species of the genus Savigniorrhipis Wunderlich, 1992 (Araneae: Linyphiidae) in the Azores (Portugal), with description of a new species. AB - Savigniorrhipis topographicus new species is described from the Azores. The synapomorphies of Savigniorrhipis are discussed along with the affinities of the genus within the Savignia-group. Given the extremely restricted and increasingly disturbed habitat, S. topographicus new species should be classified as Critically Endangered and its single forest habitat at Topo (Sao Jorge Island) should increase its current protection level to a strict nature reserve. PMID- 25113353 TI - Review of the genus Dolichosciara Tuomikoski (Diptera, Sciaridae) from China. AB - The genus Dolichosciara from China is reviewed and 17 species are recognized. Among them, eight new species, D. sparsula sp. nov., D. gracilenta sp. nov., D. oxyacantha sp. nov., D. scrobiculata sp. nov., D. tumidula sp. nov., D. rectospinosa sp. nov., D. multisetosa sp. nov. and D. qingliangfengana sp. nov. are described and seven species, D. ninae (Antonova, 1977), D. megumiae (Sasakawa, 1994), D. orcina (Tuomikoski, 1960), D. semiferruginea (Menzel, 1995), D. hippai Komarova & Vilkamaa, 2006, D. subornata (Mohrig & Menzel, 1994) and D. ornata (Winnertz, 1867) are reported for the first time from China. In addition, geographical distribution of 17 Chinese species are provided, as well as a key to all these Chinese species. This study raises the number of the species of Chinese Dolichosciara from 2 to 17. PMID- 25113354 TI - Loricaria luciae, a new species of whiptail catfish (Siluriformes: Loricariidae) from the Paraguay and lower Parana River basins of southeastern South America. AB - Loricaria luciae, new species, is described from the the rio Paraguay basin of Bolivia, Brazil, and Paraguay, south to its confluence with the rio Parana in Argentina. It is distinguished from all congeners by the following combination of characteristics: pectoral girdle entirely naked or with small isolated plates near base of pectoral fin, post-ural plate at base of caudal fin large (plate length 17.0-20.3% HL), and total lateral plates 32-33 (modally 32). The new species occurs in a variety of habitats ranging from small, seasonally intermittent streams with clear water to large, turbid rivers over sand and mud substrates. It is sympatric with at least three other species of Loricaria in the Paraguay and lower Parana drainages, including L. apeltogaster Boulenger 1895, L. coximensis Rodriguez et al. 2012, and L. simillima Regan 1904. PMID- 25113355 TI - A new species, Hemicrepidius (Miwacrepidius) rubriventris sp. nov. (Coleoptera, Elateridae, Denticollinae) from Republic of Korea. AB - The subgenus Miwacrepidius of the genus Hemicrepidius is represented by a monotypic species, H. (M.) subcyaneus (Motschulsky 1866) from Japan, and no other congener of the subgenus has been known until now. However, three female specimens of a novel species belonging to this subgenus were recently collected from the Republic of Korea. To delimitate the species boundary of the new species compared with the monotypic species, H. (M.) subcyaneus, we attempted an integrative taxonomy based on both morphological and DNA barcoding approaches. An examination of the results revealed ten diagnostic characteristics and large genetic distances, ranging from 8.40%, between these two species; therefore, we herein describe and illustrate the new species, Hemicrepidius (Miwacrepidius) rubriventris sp. nov., based on female types. PMID- 25113356 TI - Notes on Citrogramma Vockeroth and Eosphaerophoria Frey (Diptera: Syrphidae). AB - New taxonomic and distributional data on the genera Citrogramma Vockeroth, 1969 and Eosphaerophoria Frey, 1946 are presented, including descriptions of the females of Citrogramma asombrosum Mengual, 2012, Citrogramma pennardsi Mengual, 2012 and Eosphaerophoria dentiscutellata (Keiser, 1958). Modifications to published identification keys to accommodate the new information are provided for both genera. PMID- 25113357 TI - Endogean and cavernicolous Coleoptera of the Balkans. XII. New species of Paramaurops Jeannel, 1948 (Coleoptera: Staphylinidae: Pselaphinae) from Macedonia. AB - The new species of the tribe Amauropini, Paramaurops vonickai n. sp. is described from Macedonia. PMID- 25113359 TI - Revision of the subgenus Cosmiomorpha (Cosmiomorpha)(Coleoptera: Scarabaeidae: Cetoniinae). AB - A taxonomic revision of the subgenus Cosmiomorpha (Cosmiomorpha) Saunders is presented. Seven species are recognized, including four described herein, C. fortis new species, C. nigripedis new species, C. maolanensis new species, and C. cheni new species all from China. Cosmiomorpha baryi Bourgoin and C. squamulosa Schurhoff are placed as junior synonyms of C. decliva Janson, and C. angulosa Fairmaire as a synonym of C. decliva is also confirmed. Lectotypes are designated for C. decliva Janson, C. angulosa Fairmaire, and C. squamulosa Schurhoff. Color photographs and diagnoses of all species are provided, with comments on intraspecific variations. A key to males is also presented. Localities of "Siao Lou" and "Se Pin-Lou Chan" are discussed with a map. PMID- 25113360 TI - Two interstitial species of the genus Semicytherura (Crustacea: Ostracoda) from Japan, with notes on their microhabitats. AB - A new interstitial ostracod, Semicytherura uzushio sp. nov., is described from the southwest of Japan, and the details of the carapace characters of Semicytherura mukaishimensis Okubo, 1980 are redescribed. Semicytherura uzushio and S. mukaishimensis live interstitially in the intertidal and infralittoral zones, respectively. They have the smallest carapaces among the known Semicytherura species, comparable to those of other interstitial ostracods. It is thought that most of the small species belonging to this genus have an interstitial life style in marine sediments. PMID- 25113361 TI - New species of Stenodactylus (Squamata: Gekkonidae) from the Sharqiyah Sands in northeastern Oman. AB - A new species of gecko of the genus Stenodactylus (Squamata: Gekkonidae) is described from the dune desert of Al Sharqiyah Sands in northeastern Oman. Stenodactylus sharqiyahensis sp. nov. is characterized morphologically by its small size, snout shape, webbing between fingers not very extended, relatively short limbs, and scalation. It is genetically distinct in the mitochondrial DNA and the nuclear MC1R gene from Stenodactylus arabicus to which it has previously been referred. The new species seems to have a restricted distribution confined to the Sharqiyah Sands, which remain isolated from other sand deserts in Arabia. In addition, the data presented herein confirm new locality records for Stenodactylus arabicus in the easternmost limit of its distribution range in western central Oman. PMID- 25113362 TI - New species of Hypoaspis Canestrini and Coleolaelaps Berlese (Mesostigmata: Laelapidae) associated with Polyphylla olivieri Castelnau (Coleoptera: Scarabaeidae) in Iran . AB - White grubs, including Polyphylla olivieri Castelnau, are among the most economically important pests of orchard trees and other crops such as potato and sugar beet. The larvae feed on the roots of the host plants and their adults feed on the leaves. Several types of organisms are parasitic or phoretic on this pest, including three species of mites from Iran. Two new species of mites, namely Hypoaspis (Hypoaspis) surii n. sp. and Coleolaelaps massoumii n. sp. are described here from the adults of P. olivieri in Hamedan, Iran. Hypoaspis polyphyllae Khanjani & Ueckermann was previously described from the larva of this species of beetle. PMID- 25113363 TI - Description of the larva of Argia chelata Calvert, 1902 (Odonata: Coenagrionidae). AB - The larva of Argia chelata is described and figured. It falls into the group of Argia larvae with a moderately prominent ligula and two palpal seta, but it differs from its closest relatives by having labial palp with 2 setae plus one basal setella; the length of the ligula is 30% of its maximum width; basal tergites (1-5) lacking long, fine setae, mainly on midline; S8-10 mostly dark brown; paraprocts with spiniform setae on basal 0.25 and 0.55 of dorsal and ventral borders, respectively. Larvae were found in 2nd to 4th order shallow streams in cloud forest, crawling among debris, fine sand and mud where the water flow is slow or still, close to the shoreline. The larva is compared with A. lacrimans (Hagen), A. pima Garrison, and A. tonto Calvert, species apparently closely related. PMID- 25113364 TI - Cave millipedes of the United States. XIII. A new, troglobiotic species of Austrotyla from Colorado (Diplopoda, Chordeumatida, Conotylidae). AB - Austrotyla stephensoni n. sp., from Colorado, is described as the first troglobiotic species of its genus, and compared to sympatric Austrotyla coloradensis (Chamberlin 1910). A key to all Austrotyla species is provided. PMID- 25113365 TI - The genus Rhamphothrips in India (Thysanoptera: Thripidae) with description of a new species . AB - Rhamphothrips bhattii sp.n. is described from India based on specimens collected on flowers and leaves of Tabernaemontana divaricata (Apocynaceae) in the States of West Bengal and Odisha. The pronotum of this species is longer than any other known member of the genus. A key to the six species of Rhamphothrips recorded from India is provided. PMID- 25113366 TI - A new species of Mataeomera, formerly misidentified as M. obliquisigna (Hampson, 1894) from Japan (Lepidoptera, Erebidae, Boletobiinae). AB - Mataeomera Butler, 1886, currently referred to the tribe Eublemmini in Boletobiinae (Holloway 2011), was proposed by Butler (1886) to accommodate an Australian species, Mataeomera dubia Butler. This genus was once regarded as a junior synonym of Autoba Walker by Poole (1989) but resurrected by Edwards (1996). Another related genus, Catoblemma Hampson, 1910 originally proposed for Catoblemma sumbavensis Hampson, 1910 from Lesser Sunda was revised to include the Australian and East and Southeast Asian species. Edwards (1996) found the Australian species of Catoblemma and Mataeomera dubia congeneric and established the synonymy of those two genera. Following Edwards (1996), Yoshimoto (1999) transferred the Asian species of Catoblemma to Mataeomera. Mataeomera currently includes 21 species (Poole 1989; Edwards 1996; Holloway 2009). Following Holloway (2009), we note that Catoblemma appears to include several unrelated species and is probably polyphyletic. In fact, the Indo-Himalayan and East Asian species currently assigned to Mataeomera are distinct from the Australian congeners in external appearance and larval feeding habits (Sohn & Ronkay 2001; Holloway 2009). As such these may merit generic status but this possibility is still under study by the first author (JCS). PMID- 25113367 TI - Internal oral morphology in larvae of the genus Rhinella Fitzinger, 1826 (Amphibia, Anura, Bufonidae) . AB - From the 86 species allocated in the genus Rhinella, 25 have their tadpoles described and only R. arenarum, R. chrysophora, R. icterica, R. ornata, R. schneideri and R. spinulosa have aspects of the internal oral morphology evidenced. Herein, the internal oral morphology from 12 species of Rhinella distributed between the morphological groups of R. crucifer, R. granulosa, R. marina and R margaritifera is described and compared. The internal oral morphology of Rhinella is little variable in many aspects. Despite the many similarities found between the tadpoles of Rhinella, the study showed that there are characteristics that exhibit interspecific variation that can be used in the taxonomy of the genus. Important features to distinguish species were: number of infrarrostral projections; number and shape of the infralabial papillae; size, arrangement, shape and apex of the lingual papillae; shape of the buccal floor arena papillae; number of projections of the ventral velum; shape of the prenarial ridge; choanae arrangement; number and apex of the postnarial papillae; number and shape of the secondary branches on the lateral ridge papilla; buccal roof arena papillae arrangement. PMID- 25113368 TI - Description of the egg and immature stages of Potamobates anchicaya J. Polhemus & D. Polhemus, 1995 (Hemiptera: Heteroptera: Gerridae) and intersexual variation in adults. AB - The egg and five nymphal stages, of the Neotropical species Potamobates anchicaya are described and illustrated for the first time. Intra- and intersexual variation in the abdominal terminalia of apterous adults is also illustrated. Adults and nymphs were collected from three populations in southwestern Colombia. PMID- 25113370 TI - Vulcanolepas scotiaensis sp. nov., a new deep-sea scalpelliform barnacle (Eolepadidae: Neolepadinae) from hydrothermal vents in the Scotia Sea, Antarctica. AB - A new deep-sea stalked barnacle, Vulcanolepas scotiaensis sp. nov. is described from hydrothermal vents at depths of 2400-2600 metres along segments of the East Scotia Ridge and from 1400 metres in the Kemp Caldera. Both locations are areas of volcanic activity that lie on the Antarctic-South American Ocean Ridge complex near the South Sandwich Islands. This discovery confirms a wide distribution in southern seas for Vulcanolepas, complementing the previous records from deep-sea vents in the Lau Basin and Kermadec Ridge in the southwest Pacific, and the Pacific Antarctic Ridge in the southeast Pacific. V. scotiaensis sp. nov., the third described species of Vulcanolepas shows an extraordinary range in morphology, requiring a reassessment of the original diagnosis for Vulcanolepas. Although the morphological envelope of V. scotiaensis sp. nov. includes representatives with a peduncle to capitulum ratio similar to that observed in most neolepadines, the peduncle generally shows greater proportional length than in species in any neolepadine genus except Leucolepas; it is distinguished from other species of Vulcanolepas by a broader capitulum, much smaller imbricating scales on the peduncle and more ornamented capitulum plates. The morphological diversity of V. scotiaensis sp. nov. is interpreted as having arisen due to abrupt changes in water temperature.LSID: urn:lsid:zoobank.org:act:AA2AFDA5-0B08 466A-A584-D3FDBDE9DA61. PMID- 25113369 TI - Stictonectes abellani sp. n. (Coleoptera: Dytiscidae: Hydroporinae) from the Iberian Peninsula, with notes on the phylogeny, ecology and distribution of the Iberian species of the genus. AB - Stictonectes abellani sp. n. is described from the Iberian Peninsula. On average, the new species is larger and the colouration of the upper surface darker than in most other species of the genus. Seemingly the species has been confounded with others in the past, particularly S. optatus (Seidlitz, 1887). Males can be separated from externally similar species by studying the shape of the parameres. Additionally, the anterior margin of the clypeus is provided with a distinct rim in both sexes, which is absent or only weakly present in other species. The habitus and the male genitalia of the new species are illustrated, and compared with those of S. optatus. External morphological differences from other members of the genus are discussed. According to studies of the molecular phylogeny, based on fragments of four mitochondrial genes, S. abellani sp. n. is clearly separated from previously described species of Stictonectes Brinck, 1943, apparently being relatively basal within the genus. The new species is rather widely distributed in the south-western part of the Iberian Peninsula, inhabiting pools in small temporary siliceous streams. We provide distributional maps for all eight Iberian Stictonectes and estimate the potential distributional areas of the new species and the other two endemic Iberian species S. occidentalis Fresneda & Fery, 1990 and S. rebeccae Bilton, 2011, based on environmental niche modelling. PMID- 25113371 TI - Two new species of Gieysztoria (Platyhelminthes, Rhabdocoela, Dalyelliidae) from a freshwater artificial lake in Shenzhen, China. AB - Two new species of the "Aequales" of genus Gieysztoria were collected and described from an artificial lake on the Shenzhen University campus. Gieysztoria bimaculata n. sp., is distinguished based on two groups clavate pigmentations dorsally between the pharynx and intestine, and has a sclerotic stylet comprising a proximal girdle with 40-46 distal dagger-shape spines, thus has the maximum number of spines within "Aequales" group. Gieysztoria guangdongensis n. sp. has a sclerotic stylet with a proximal girdle and 18 distal blade-shaped spines. Comparison with similar species based mainly on stylet morphology suggests that Gieysztoria bimaculata n. sp. and Gieysztoria guangdongensis n. sp. are apparently different from the known species of Gieysztoria in this moment. In addition, the stability of the amount of distal spines of "Aequales" species is briefly discussed. PMID- 25113372 TI - Notes on the genus Libellulosoma Martin, 1906, and related genera (Odonata: Anisoptera: Corduliidae). AB - The holotype of Libellulosoma minuta, until now regarded as the unique specimen of this monotypic genus and considered lost for half a century, was found again in the dragonfly collection of the Museum National d'Histoire Naturelle in Paris. A second specimen, also from Madagascar (probably East Madagascar) was found in the collection Rene Martin together with the holotype. A redescription, including the structure of the secondary copulatory apparatus, is provided. The genus Libellulosoma is closely related to the genera Pentathemis and Aeschnosoma, and its membership in the clade Aeschnosomata is well supported. Evidence from biogeography, the fossil record, and phylogeny indicates that this group, possible sister group of remaining Corduliidae s.s., was probably already present in the Early Cretaceous. PMID- 25113373 TI - Two new species of Microvelia Westwood, 1834 (Hemiptera: Heteroptera: Veliidae) from Colombia, with a key to Colombian species. AB - Only six species of Microvelia have been recorded from Colombia up to the present, namely M. ancona, M. hinei, M. leucothea, M. longipes, M. panamensis, and M. pulchella. Microvelia inguapi sp. n. and M. piedrancha sp. n. are herein described and compared with similar species. An identification key to the Colombian species of Microvelia is presented. PMID- 25113374 TI - Chriolepis bilix, a new species of goby (Teleostei: Gobiidae) from deep waters of the western Atlantic. AB - A new species of seven-spined goby of the genus Chriolepis is described from four specimens from four widely separate western Atlantic localities (Little Bahama Bank; off southwestern Florida; Tobago Island; and northeastern Colombia) from depths ranging from 62 to 138 m. The species is distinct from all other western Atlantic species currently assigned to the genus Chriolepis in having a fully scaled body, the first two dorsal-fin spines greatly elongated in both sexes, especially so in females, and two anal-fin pterygiophores inserted anterior to the first haemal spine. It differs from members of the similar genus Varicus in having branched pelvic-fins rays, a longer fifth pelvic-fin ray and more numerous meristic elements. It closely resembles Chriolepis atrimelum, known from a similar depth at Isla del Coco in the eastern Pacific Ocean. PMID- 25113376 TI - Reflections on eleven years with PCCP. PMID- 25113375 TI - FAK and paxillin dynamics at focal adhesions in the protrusions of migrating cells. AB - Cell migration requires the fine spatiotemporal integration of many proteins that regulate the fundamental processes that drive cell movement. Focal adhesion (FA) dynamics is a continuous process involving coordination between FA and actin cytoskeleton, which is essential for cell migration. We studied the spatiotemporal relationship between the dynamics of focal adhesion kinase (FAK) and paxillin at FAs in the protrusion of living endothelial cells. Concurrent dual-color imaging showed that FAK was assembled at FA first, which was followed by paxillin recruitment to the FA. By tracking and quantifying FAK and paxillin in migrating cells, the normalized FAK/Paxillin fluorescence intensity (FI) ratio is > 1 (~ 4 fold) at cell front, ~ 1 at cell center, and < 1 at cell rear. The significantly higher FAK FI than paxillin FI at cell front indicates that the assembly of FAK-FAs occurs ahead of paxillin at cell front. To determine the time difference between the assemblies of FAK and paxillin at nascent FAs, FAs containing both FAK and paxillin were quantified by image analysis and time correlation. The results show that FAK assembles at the nascent FAs earlier than paxillin in the protrusions at cell front. PMID- 25113379 TI - Nasal MRSA colonization: impact on surgical site infection following spine surgery. AB - BACKGROUND: Prior studies published in the cardiothoracic, orthopedic and gastrointestinal surgery have identified the importance of nasal (methicillin resistant Staphylococcus aureus) MRSA screening and subsequent decolonization to reduce MRSA surgical site infection (SSI). This is the first study to date correlating nasal MRSA colonization with postoperative spinal MRSA SSI. OBJECTIVE: To assess the significance of nasal MRSA colonization in the setting of MRSA SSI. METHODS: A retrospective electronic chart review of patients from year 2011 to June 2013 was conducted for patients with both nasal MRSA colonization within 30 days prior to spinal surgery. Patients who tested positive for MRSA were put on contact isolation protocol. None of these patients received topical antibiotics for decolonization of nasal MRSA. RESULTS: A total of 519 patients were identified; 384 negative (74%), 110 MSSA-positive (21.2%), and 25 (4.8%) MRSA-positive. Culture positive surgical site infection (SSI) was identified in 27 (5.2%) cases and was higher in MRSA-positive group than in MRSA negative and MSSA-positive groups (12% vs. 5.73% vs. 1.82%; p=0.01). The MRSA SSI rate was 0.96% (n=5). MRSA SSI developed in 8% of the MRSA-positive group as compared to only in 0.61% of MRSA-negative group, with a calculated odds ratio of 14.23 (p=0.02). In the presence of SSI, nasal MRSA colonization was associated with MRSA-positive wound culture (66.67 vs. 12.5%; p<0.0001). CONCLUSION: Preoperative nasal MRSA colonization is associated with postoperative spinal MRSA SSI. Preoperative screening and subsequent decolonization using topical antibiotics may help in decreasing the incidence of MRSA SSI after spine surgery. Nasal MRSA+ patients undergoing spinal surgery should be informed regarding their increased risk of developing surgical site infection. PMID- 25113380 TI - The midline suboccipital subtonsillar approach to the cerebellomedullary cistern and its structures: anatomical considerations, surgical technique and clinical application. AB - OBJECTIVE: Lesions of the cerebellomedullary cistern lateral to the lower brainstem in an area extending from the foraminae of Luschka to the foramen magnum are rare and can be caused by various sources. There is no consensus on an ideal surgical approach. We describe the anatomical features and the surgical technique of the midline suboccipital subtonsillar (STA) approach to the cerebellomedullary cistern and its pathologies. METHODS: The study was performed on three alcohol (ETOH)-fixed specimens (6 sides), and the technique of the approach was highlighted. The tonsillar retraction needed to view the important structures was measured. Additionally, the records of 31 patients who underwent the STA procedure were evaluated. We provide three clinical cases as examples. RESULTS: Tonsillar retraction of 0.3cm (SD+/-0.1cm) exposed the PICA with its telo-velo-tonsillar and cortical branches. Retraction of 0.4cm (SD+/-0.2cm) exposed the spinal root of CN XI. Retraction of 0.9cm (SD+/-0.01cm) exposed the hypoglossal canal. Retraction of 1.3cm (SD+/-0.2cm) exposed the root exit zone of the glossopharyngeal nerve. Retraction of 1.6cm (SD+/-0.3cm) exposed the jugular foramen (JF), and retraction of 2.4cm (SD+/-0.2cm) exposed the inner auditory canal (IAC). In all of the selected cases, the pathology could be reached and exposed using the STA. CONCLUSIONS: We recommend STA as a straightforward, easy to-learn and therefore time-saving and safe procedure compared with other standard approaches to the cerebellomedullary cistern and its pathologies. PMID- 25113377 TI - Transcriptome sequencing and genome-wide association analyses reveal lysosomal function and actin cytoskeleton remodeling in schizophrenia and bipolar disorder. AB - Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental disorders with high heritability. Clinicians have long noticed the similarities of clinic symptoms between these disorders. In recent years, accumulating evidence indicates some shared genetic liabilities. However, what is shared remains elusive. In this study, we conducted whole transcriptome analysis of post-mortem brain tissues (cingulate cortex) from SCZ, BPD and control subjects, and identified differentially expressed genes in these disorders. We found 105 and 153 genes differentially expressed in SCZ and BPD, respectively. By comparing the t-test scores, we found that many of the genes differentially expressed in SCZ and BPD are concordant in their expression level (q?0.01, 53 genes; q?0.05, 213 genes; q?0.1, 885 genes). Using genome-wide association data from the Psychiatric Genomics Consortium, we found that these differentially and concordantly expressed genes were enriched in association signals for both SCZ (P<10(-7)) and BPD (P=0.029). To our knowledge, this is the first time that a substantially large number of genes show concordant expression and association for both SCZ and BPD. Pathway analyses of these genes indicated that they are involved in the lysosome, Fc gamma receptor-mediated phagocytosis, regulation of actin cytoskeleton pathways, along with several cancer pathways. Functional analyses of these genes revealed an interconnected pathway network centered on lysosomal function and the regulation of actin cytoskeleton. These pathways and their interacting network were principally confirmed by an independent transcriptome sequencing data set of the hippocampus. Dysregulation of lysosomal function and cytoskeleton remodeling has direct impacts on endocytosis, phagocytosis, exocytosis, vesicle trafficking, neuronal maturation and migration, neurite outgrowth and synaptic density and plasticity, and different aspects of these processes have been implicated in SCZ and BPD. PMID- 25113378 TI - Proneurogenic Group II mGluR antagonist improves learning and reduces anxiety in Alzheimer Abeta oligomer mouse. AB - Proneurogenic compounds have recently shown promise in some mouse models of Alzheimer's pathology. Antagonists at Group II metabotropic glutamate receptors (Group II mGluR: mGlu2, mGlu3) are reported to stimulate neurogenesis. Agonists at those receptors trigger gamma-secretase-inhibitor-sensitive biogenesis of Abeta42 peptides from isolated synaptic terminals, which is selectively suppressed by antagonist pretreatment. We have assessed the therapeutic potential of chronic pharmacological inhibition of Group II mGluR in Dutch APP (Alzheimer's amyloid precursor protein E693Q) transgenic mice that accumulate Dutch amyloid beta (Abeta) oligomers but never develop Abeta plaques. BCI-838 is a clinically well-tolerated, orally bioavailable, investigational prodrug that delivers to the brain BCI-632, the active Group II mGluR antagonist metabolite. Dutch Abeta oligomer-forming APP transgenic mice (APP E693Q) were dosed with BCI-838 for 3 months. Chronic treatment with BCI-838 was associated with reversal of transgene related amnestic behavior, reduction in anxiety, reduction in levels of brain Abeta monomers and oligomers, and stimulation of hippocampal neurogenesis. Group II mGluR inhibition may offer a unique package of relevant properties as an Alzheimer's disease therapeutic or prophylactic by providing both attenuation of neuropathology and stimulation of repair. PMID- 25113381 TI - A case of contrecoup skull fracture caused by mild head injury. PMID- 25113384 TI - Pilgrims. PMID- 25113383 TI - Association between fasting serum glucose levels and incidence of colorectal cancer in Korean men: the Korean Cancer Prevention Study-II. AB - INTRODUCTION: The incidence of colorectal cancer (CRC) is steadily increasing worldwide. Numerous studies have demonstrated that diabetes mellitus is related to an increased risk of CRC; however, the association between impaired fasting glucose and CRC is unclear. Therefore, we evaluated the correlation between fasting serum glucose (FSG) levels and the incidence of CRC, which can be used to develop novel methods for preventing CRC. METHODS: A total of 175,677 individuals from the Korean Metabolic Syndrome Research Initiative study were enrolled between 2004 and 2011. The incidence of CRC was assessed during a mean follow-up of 4.7 years. Hazard ratios (HR) for CRC according to FSG levels were calculated with the Cox proportional hazard model adjusted for age, sex, body mass index, smoking status, alcohol consumption, and regular exercise. RESULTS: The risk of developing CRC in subjects with high FSG was significant (HR, 1.45; 95% confidence interval [CI], 1.10-1.90), and the risk was higher in men (HR, 1.51; 95% CI, 1.12-2.05). The HR of rectal cancer, but not colon cancer, was significantly higher both in the total population and in men in the high FSG group. CONCLUSIONS: The incidence of CRC positively correlated with FSG levels in men. Rectal cancer incidence was especially correlated with high FSG in the site specific analysis. Therefore, serum glucose levels maybe a potential marker of colorectal cancer. Early detection and intervention for controlling elevated glucose levels may be indicated as a way to prevent carcinogenesis. PMID- 25113382 TI - MAG-EPA and 17,18-EpETE target cytoplasmic signalling pathways to reduce short term airway hyperresponsiveness. AB - This study was aimed to investigate the role of eicosapentaenoic acid monoacylglyceride (MAG-EPA) and 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) on the regulation of contractile reactivity and nuclear protein expression in 72-h cultured and TNF-alpha-treated guinea pig tracheal rings. Tension measurements performed on native tissues demonstrated that the cytochrome P-450 epoxygenase (CYP450)-dependent EPA metabolite, 17,18-EpETE, displayed a higher potency than MAG-EPA in inhibiting U-46619-induced tone. Calphostin C (a PKC inhibitor), whether in association or not with MAG-EPA or 17,18-EpETE, had no further effect, while 17,18-EpETE and Y-27632 (a Rho kinase inhibitor) yielded additive effects. Of note, MAG-EPA and 17,18-EpETE pre-treatments normalized the contractile responses to broncho-constrictive agents in 72-h-cultured trachea. The enhanced expression of TNF-alpha, P-p65-nuclear factor kappaB (NF)-kappaB, c-fos and c-Jun in 72-h-cultured tissues likely contributed to the hyperresponsiveness. beta Escin-permeabilized preparations demonstrated that 17,18-EpETE abolished Ca(2+) hypersensitivity, suggesting a blunting of PKC and/or Rho kinase activation. Lastly, activation of NF-kappaB and activating protein-1 (AP-1) signalling by exogenous TNF-alpha markedly increased the contractile response to MCh, through an increase in 17-kDa PKC-potentiated inhibitory protein of PP1 (CPI-17) phosphorylation and IkappaBalpha degradation. Dual incubation of 17,18-EpETE with calphostin C or Y-27632 induced cumulative inhibitory effects on MCh responses in TNF-alpha-incubated tracheal rings. 17,18-EpETE also reduced the detection level of P-p65-NF-kappaB and AP-1 subunits. The present data provide evidence that MAG EPA, through its bioactive metabolite, represents a prospective pharmacological target in respiratory diseases. PMID- 25113385 TI - Pseudohongiella acticola sp. nov., a novel gammaproteobacterium isolated from seawater, and emended description of the genus Pseudohongiella. AB - A Gram-negative, aerobic, non-spore-forming and rod-shaped or ovoid bacterial strain able to move by a single polar flagellum, designated GBSW-5(T), was isolated from seawater in the East Sea, South Korea. Strain GBSW-5(T) was found to grow optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 2.0% (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences revealed that strain GBSW-5(T) clustered with the type strain of Pseudohongiella spirulinae. Strain GBSW-5(T) exhibited the highest 16S rRNA gene sequence similarity value (96.4%) to the type strain of P. spirulinae, and of less than 91.0% sequence similarities to the type strains of other recognized species. Strain GBSW-5(T) was found to contain Q-8 as the predominant ubiquinone and C(18:1)omega7c and summed feature 3 (C(16:1)omega7c and/or C(16:1)omega6c) as the major fatty acids. The major polar lipids of strain GBSW-5(T) were identified as phosphatidylglycerol, phosphatidylethanolamine and phosphatidylmonomethylethanolamine. The DNA G+C content of strain GBSW-5(T) was determined to be 59.1 mol%. The differential phenotypic properties, together with the phylogenetic distinctiveness, revealed that strain GBSW-5(T) is separated from P. spirulinae. On the basis of the data presented, strain GBSW-5(T) is considered to represent a novel species of the genus Pseudohongiella, for which the name Pseudohongiella acticola sp. nov. is proposed. The type strain is GBSW 5(T) (= KCTC 42131(T) = CECT 8627(T)). An emended description of the genus Pseudohongiella is also given. PMID- 25113386 TI - Granulosicoccus undariae sp. nov., a member of the family Granulosicoccaceae isolated from a brown algae reservoir and emended description of the genus Granulosicoccus. AB - A Gram-stain-negative, aerobic, non-flagellated and coccoid bacterial strain, W BA3(T), which was isolated from a brown algae reservoir in Wando of South Korea, was characterized taxonomically. Strain W-BA3(T) was found to grow optimally at 30 degrees C, at pH 7.0-8.0 and in presence of 2.0 % (w/v) NaCl. In the neighbour-joining phylogenetic tree based on 16S rRNA gene sequences, strain W BA3(T) clustered with the type strains of Granulosicoccus antarcticus and Granulosicoccus coccoides, with which it exhibited sequence similarity values of 98.4-99.3 %. Sequence similarity values of strain W-BA3(T) to the type strains of the other recognized species were less than 90.2 %. Strain W-BA3(T) was found to contain Q-8 as the predominant ubiquinone and summed feature 3 (C16:1 omega7c and/or C16:1 omega6c), C18:1 omega7c and C16:0 as the major fatty acids. The major polar lipids of strain W-BA3(T), which were identified as phosphatidylethanolamine and phosphatidylglycerol, were similar to those of the type strains of G. antarcticus and G. coccoides. The DNA G+C content of strain W BA3(T) was 56.0 mol % and its mean DNA-DNA relatedness values with the type strains of G. coccoides and G. antarcticus were 27 and 17 %, respectively. Differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, demonstrated that strain W-BA3(T) is separated from the two Granulosicoccus species. On the basis of the data presented, strain W-BA3(T) is considered to represent a novel species of the genus Granulosicoccus, for which the name Granulosicoccus undariae sp. nov. is proposed. The type strain is W BA3(T) (=KCTC 42134(T) = NBRC 110411(T)). An emended description of the genus Granulosicoccus is also proposed. PMID- 25113387 TI - How 2 txt: an exploration of crafting public health messages in SMS. AB - BACKGROUND: Health care providers are an important target audience for public health emergency preparedness, response and recovery communications. Short Message Service or text messaging to cell phones may be a promising supplemental or alternative technique for reaching health care providers with time-sensitive public health information. However, studies to date have yet to investigate the message content and formatting requirements of providers with respect to public health alerts and advisories or sought to understand how to meet these needs using Short Message Service technology. METHODS: Data collection was completed using a two-part online survey. In the first part, health care providers identified their use of different technologies for receiving information and provided input on the message components most important in a public health message. In the second part, health care providers participated in an exercise in which they shortened three public health emergency messages, ranging from 2024 2828 characters per message, to meet the 160-character limitation for text delivery. Results were analyzed to determine associations between provider types, age ranges, gender, access to various media (text, email, fax, social media, etc.), and smart phone ownership. RESULTS: The following components were most frequently selected as essential for a public health message: Topic, Recommendation, Geographic Location, Signs & Symptoms, Population Affected, and Link to Additional Information. There was no statistically significant association between message component selection and provider type, age ranges, or gender. In the message conversion exercise, we found a statistically significant association between providers who reported receiving information by SMS and/or smart phone ownership and including a link to additional information in the converted message, ranging from 61% to over 72% on a per message analysis. CONCLUSIONS: A substantive recommendation derived from this study is that public health agencies include a link to additional website information when sending messages in SMS format. SMS could be a useful public health tool for communicating with health care providers but further investigation of how to effectively use SMS and other mobile technologies is needed to inform public health decisions regarding adoption of messaging systems utilizing these newer technologies. PMID- 25113389 TI - 3D Strain helps relating LV function to LV and structure in athletes. AB - INTRODUCTION: The evaluation of cardiac contraction could benefit from a connection with the underlying helical structure of cardiac fibers in athletes either completely healthy or with minor common cardiopathies like Bicuspid Aortic Valve (BAV). This study aims to exploit the potential role of 3D strain to improve the physiological understanding of LV function and modification due to physical activity as a comparative model. METHODS: Three age-matched groups of young (age 20.3 +/- 5.4) individuals are prospectively enrolled: 15 normal healthy subjects, 15 healthy athletes, and 20 athletes with bicuspid aortic valve (BAV). All subjects underwent echocardiographic examination and both 2D and 3D strain analysis. RESULTS: All echo parameters were within the normal range in the three groups. Global values of end-systolic longitudinal and circumferential strain, assesses by either 2D or 3D analysis, were not significantly different. The 3D strain analysis was extended in terms of principal and secondary strain (PS, SS). Global PS was very similar, global SS was significantly higher in athletes and displays a modified time course. The comparative analysis of strain lines pattern suggests that the enhancement of LV function is achieved by a more synchronous recruitment of both left- and right-handed helical fibers. CONCLUSIONS: 3D strain analysis allows a deeper physiological understanding of LV contraction in different types of athletes. Secondary strain, only available in 3D, identifies increase of performances due to physical activity; this appears to follow from the synergic activation of endocardial and epicardial fibers. PMID- 25113388 TI - Nursing-sensitive indicators: a concept analysis. AB - AIM: To report a concept analysis of nursing-sensitive indicators within the applied context of the acute care setting. BACKGROUND: The concept of 'nursing sensitive indicators' is valuable to elaborate nursing care performance. The conceptual foundation, theoretical role, meaning, use and interpretation of the concept tend to differ. The elusiveness of the concept and the ambiguity of its attributes may have hindered research efforts to advance its application in practice. DESIGN: Concept analysis. DATA SOURCES: Using 'clinical indicators' or 'quality of nursing care' as subject headings and incorporating keyword combinations of 'acute care' and 'nurs*', CINAHL and MEDLINE with full text in EBSCOhost databases were searched for English language journal articles published between 2000-2012. Only primary research articles were selected. METHODS: A hybrid approach was undertaken, incorporating traditional strategies as per Walker and Avant and a conceptual matrix based on Holzemer's Outcomes Model for Health Care Research. RESULTS: The analysis revealed two main attributes of nursing-sensitive indicators. Structural attributes related to health service operation included: hours of nursing care per patient day, nurse staffing. Outcome attributes related to patient care included: the prevalence of pressure ulcer, falls and falls with injury, nosocomial selective infection and patient/family satisfaction with nursing care. CONCLUSION: This concept analysis may be used as a basis to advance understandings of the theoretical structures that underpin both research and practical application of quality dimensions of nursing care performance. PMID- 25113390 TI - The advances and perspectives of recombinant protein production in the silk gland of silkworm Bombyx mori. AB - The silk gland of silkworm Bombyx mori, is one of the most important organs that has been fully studied and utilized so far. It contributes finest silk fibers to humankind. The silk gland has excellent ability of synthesizing silk proteins and is a kind tool to produce some useful recombinant proteins, which can be widely used in the biological, biotechnical and pharmaceutical application fields. It's a very active area to express recombinant proteins using the silk gland as a bioreactor, and great progress has been achieved recently. This review recapitulates the progress of producing recombinant proteins and silk-based biomaterials in the silk gland of silkworm in addition to the construction of expression systems. Current challenges and future trends in the production of valuable recombinant proteins using transgenic silkworms are also discussed. PMID- 25113391 TI - High temperature superconducting FeSe films on SrTiO3 substrates. AB - Interface enhanced superconductivity at two dimensional limit has become one of most intriguing research directions in condensed matter physics. Here, we report the superconducting properties of ultra-thin FeSe films with the thickness of one unit cell (1-UC) grown on conductive and insulating SrTiO3 (STO) substrates. For the 1-UC FeSe on conductive STO substrate (Nb-STO), the magnetization versus temperature (M-T) measurement shows a drop crossover around 85 K. For the FeSe films on insulating STO substrate, systematic transport measurements were carried out and the sheet resistance of FeSe films exhibits Arrhenius TAFF behavior with a crossover from a single-vortex pinning region to a collective creep region. More intriguing, sign reversal of Hall resistance with temperature is observed, demonstrating a crossover from hole conduction to electron conduction above TC in 1-UC FeSe films. PMID- 25113392 TI - Re: Impact of pelvicalyceal anatomy in treatment with shock wave lithotripsy and flexible ureterorenoscopy of lower pole renal stones. PMID- 25113396 TI - Interconvertible living radical and cationic polymerization through reversible activation of dormant species with dual activity. AB - The polymerization of vinyl monomers generally requires the selection of an appropriate single intermediate, whereas in copolymerization, the selection of the comonomer is limited by the intermediate. Herein, we propose interconvertible dual active species that can connect comonomers through different mechanisms to produce specific comonomer sequences in a single polymer chain. More specifically, two different stimuli, that is, a radical initiator and a Lewis acid, are used to activate the common dormant C-SC(S)Z group into radical and cationic species, thereby inducing interconvertible radical and cationic copolymerization of acrylate and vinyl ether to produce a copolymer chain that consists of radically and cationically polymerized segments. The dual reversible activation provides control over molecular weights and multiblock copolymers with tunable segment lengths. PMID- 25113394 TI - The internalizing pathway to adolescent substance use disorders: mediation by ruminative reflection and ruminative brooding. AB - Two subtypes of rumination were examined in relationship to substance use and substance use disorders in adolescents. In the 8th and 9th grade, 521 adolescents completed measures assessing depressive symptoms, conduct problems, and reflective and brooding subtypes of rumination. In 12th grade, adolescents reported substance use and were administered the substance use disorders modules from the DISC. Path analyses conducted with data from 428 participants indicated that neither depression nor rumination variables significantly affected the presence of substance use. However, indirect effects of depression through reflection and brooding were differentially related to risk of developing substance use disorders, with brooding positively associated with Marijuana Use Disorders, and reflection negatively related to both Marijuana and Alcohol Use Disorders. Pathways did not differ by sex. These findings suggest that promoting self-reflection may be an effective strategy to prevent and intervene with the development of problematic substance use. PMID- 25113395 TI - Newcomers in a hazardous environment: a qualitative inquiry into sex worker vulnerability to HIV in Bali, Indonesia. AB - BACKGROUND: Women new to sex work and those with a greater degree of mobility have higher risk of HIV infection. Using social capital as a theoretical framework, we argue that better understanding of the interactions of micro-level structural factors can be valuable in reshaping and restructuring health promotion programmes in Bali to be more responsive to the concerns and needs of newcomer and mobile female sex workers (FSWs). METHODS: We conducted interviews with 11 newcomer FSWs (worked < six months), 9 mobile FSWs (experienced but worked at the current brothel < six months), and 14 senior FSWs (experienced and worked at current brothel > six months). The interviews explored women's experience of sex work including how and why they came to sex work, relationships with other FSWs and their HIV prevention practices. RESULTS: A thematic framework analysis revealed newcomer FSWs faced multiple levels of vulnerability that contributed to increased HIV risk. First, a lack of knowledge and self-efficacy about HIV prevention practices was related to their younger age and low exposure to sexual education. Second, on entering sex work, they experienced intensely competitive working environments fuelled by economic competition. This competition reduced opportunities for positive social networks and social learning about HIV prevention. Finally, the lack of social networks and social capital between FSWs undermined peer trust and solidarity, both of which are essential to promote consistent condom use. For example, newcomer FSWs did not trust that if they refused to have sex without a condom, their peers would also refuse; this increased their likelihood of accepting unprotected sex, thereby increasing HIV risk. CONCLUSIONS: Public health and social welfare interventions and programmes need to build social networks, social support and solidarity within FSW communities, and provide health education and HIV prevention resources much earlier in women's sex work careers. PMID- 25113398 TI - Prognostic significance of perineural invasion in stage IIA colon cancer. AB - BACKGROUND: Perineural invasion (PNI) may influence the prognosis of colon cancer, but little is known about its predictive value. The aim of this study was to reveal the role of PNI in predicting prognosis after curative resection of colon cancer, especially T3N0. METHODS: Two hundred and fifty-five patients who underwent curative resection for colon cancer at Samsung Medical Center and were later diagnosed with stage T3N0 by a pathological report between November 2004 and December 2007 were retrospectively recruited into the study. RESULTS: Among the 255 patients, 156 were male and 99 were female. The mean age was 61 years (range, 25 to 88 years). The most common tumour location was the sigmoid colon (93 patients, 36.5%). The median follow-up period was 61 months (range, 1 to 98 months). PNI was detected in 18 patients (7.1%). Adjuvant chemotherapy was performed in 205 patients (80.4%). The 5-year disease-free survival rate was greater for patients with PNI negative tumours compared with those with PNI positive tumours (92.0% versus 76.0%, P = 0.025). Adjuvant chemotherapy was not associated with significant differences in survival rate (94.8% versus 96.9%, P = 0.625). On multivariate analysis, PNI was an independent prognostic factor for disease-free and overall survival (P = 0.046, hazard ratio (HR) = 3.113, 95% confidence interval (CI) = 1.020-9.505 and P = 0.019, HR = 9.395, 95% CI = 1.453 60.755 respectively). CONCLUSIONS: PNI is the only significant prognostic factor affecting disease-free and overall survival in patients with T3N0 colon cancer. PMID- 25113399 TI - Low cord blood Foxp3/CD3gamma mRNA ratios: a marker of increased risk for allergy development. AB - BACKGROUND: Data from birth cohort studies suggest that increased cord blood total IgE and reduced cord blood regulatory T cells increase the risk of developing allergic sensitization and atopic dermatitis. OBJECTIVE: We here addressed whether serum total IgE and hen's egg-specific IgE levels at birth and at age 1 year differed between healthy and allergic children in a Belgian birth cohort (FONIA). We furthermore studied whether these parameters as well as cord blood Foxp3/CD3gamma mRNA levels might predict the allergic outcome. METHODS AND RESULTS: Children (n = 84) were clinically assessed at the ages of 6, 12, 18, and 24 months and at 6 years. Cord blood total IgE levels above 0.35 kU/L predicted early (i.e. before or at the age of 2 years) allergy development. Presence of serum IgE antibodies to hen's egg (cut-off 0.05 Ua/mL) at the age of 1 year was associated with early as well as late (i.e. between the age of 2 and 6 years) allergy development. Cord blood Foxp3/CD3gamma mRNA ratios were significantly lower in early allergic children and levels below 0.32 predicted the allergic outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Low cord blood Foxp3/CD3gamma mRNA ratios are highly predictive for early allergy development, whereas specific IgE levels to hen's egg white above 0.05 Ua/mL at age 1 year predict allergy development in general. PMID- 25113397 TI - Kindergarteners' self-reported social inhibition and observed social reticence: moderation by adult-reported social inhibition and social anxiety disorder symptoms. AB - Prevention of later anxiety problems would best be accomplished by identifying at risk children early in development. For example, children who develop Social Anxiety Disorder (SAD) may show social withdrawal in the form of social inhibition (i.e., shyness with unfamiliar adults and peers) at school entry. Although the use of children's perceptions of their own social inhibition would provide insight into early risk, the utility of young children's self-reports remains unclear. The current study examined whether children deemed more extreme on social inhibition or social anxiety by adult report provided self-report of social inhibition that related to observed social reticence in the laboratory. Participants included 85 kindergarten children (36 female, 49 male), their parents, and their teachers. Moderation analyses revealed that children's self reported social inhibition related significantly to observed social reticence under the conditions of high parent-reported social inhibition, high teacher reported social inhibition, and high SAD symptoms. These results suggest that the most inhibited children are aware of their behavior and can report it in a meaningfully way as young as kindergarten age. PMID- 25113400 TI - Involvement of the NF-kB/p50/Bcl-3 complex in response to antiangiogenic therapy in a mouse model of metastatic renal cell carcinoma. AB - Renal cell carcinoma (RCC) represents approximately 2-3% of human malignancies. Nuclear transcription factor kB (NF-kB) is composed of a family of transcription factors that have been associated with the development and progression of RCC. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we evaluated the expression of NF-kB in metastatic tumor cells from animals treated with ES. Balb/c-bearing Renca-EGFP cells were treated with NIH/3T3-LendSN or NIH/3T3-LXSN cells as a control. At the end of the in vivo experiment, plasma Renca-EGFP-sorted cells and tissue lung samples were collected. A real-time PCR array for NF-kappaB target genes revealed that ES therapy led to down regulation of Bcl-3 (P<0.031), NF-kB1 (P<0.001) and c-Rel (P<0.004) in the ES-treated group. Using an electrophoretic mobility shift assay (EMSA), we observed a reduction in NF-kB binding activity in ES-treated Renca-EGP cells. Furthermore, a supershift assay showed a clear shift of the NF-kB DNA band in samples incubated with a p50 antibody. By immunohistochemistry analysis, ES treatment resulted in a significant reduction in expression of p50. (ES vs. control P<0.05). The immunoprecipitation experiments confirmed the presence of a p50/Bcl-3 complex in nuclear extracts from cells of metastatic lung tissues. Our findings indicate that p50 and Bcl-3 plays a regulatory role in gene transcription in RCC. PMID- 25113401 TI - Effective utilization of flue gases in raceway reactor with event-based pH control for microalgae culture. AB - This work addresses effective utilization of flue gases through the proper pH control in raceway reactors. The pH control problem has been addressed with an event-based control approach using a Generalized Predictive Controller (GPC) with actuator deadband. Applying this control strategy it is possible to reduce the control effort, and at the same time saving control resources. In the pH process case, the event-based controller with actuator deadband can be tuned to supply only necessary amount of CO2 to keep the pH close to its optimal value. On the other hand, the evaluated control algorithm significantly improves the pH control accuracy, what has a direct influence on biomass production. In order to test the performance of the event-based GPC controller, several experiments have been performed on a real raceway reactor. Additionally, several control performance indexes have been used to compare the analyzed technique with commonly used on/off controller. PMID- 25113403 TI - Instrumentation for capillary electrophoresis and microchip electrophoresis. PMID- 25113393 TI - The hidden history of the snowshoe hare, Lepus americanus: extensive mitochondrial DNA introgression inferred from multilocus genetic variation. AB - Hybridization drives the evolutionary trajectory of many species or local populations, and assessing the geographic extent and genetic impact of interspecific gene flow may provide invaluable clues to understand population divergence or the adaptive relevance of admixture. In North America, hares (Lepus spp.) are key species for ecosystem dynamics and their evolutionary history may have been affected by hybridization. Here we reconstructed the speciation history of the three most widespread hares in North America - the snowshoe hare (Lepus americanus), the white-tailed jackrabbit (L. townsendii) and the black-tailed jackrabbit (L. californicus) - by analysing sequence variation at eight nuclear markers and one mitochondrial DNA (mtDNA) locus (6240 bp; 94 specimens). A multilocus-multispecies coalescent-based phylogeny suggests that L. americanus diverged ~2.7 Ma and that L. californicus and L. townsendii split more recently (~1.2 Ma). Within L. americanus, a deep history of cryptic divergence (~2.0 Ma) was inferred, which coincides with major speciation events in other North American species. While the isolation-with-migration model suggested that nuclear gene flow was generally rare or absent among species or major genetic groups, coalescent simulations of mtDNA divergence revealed historical mtDNA introgression from L. californicus into the Pacific Northwest populations of L. americanus. This finding marks a history of past reticulation between these species, which may have affected other parts of the genome and influence the adaptive potential of hares during climate change. PMID- 25113402 TI - Enhanced removal of COD and color from landfill leachate in a sequential bioreactor. AB - In the present study, a sequential treatment process was carried out using a fungal sp. (Phanerochaete sp.) followed by a bacterial sp. (Pseudomonas sp.) for the degradation and detoxification of contaminants in landfill leachate. The process was optimized using Box-Behnken design (BBD) and response surface methodology (RSM) for three variables (C source, N source and duration), while monitoring two responses (% COD and color removal). After treatment in a bioreactor under optimized conditions, enhanced removal of COD (76.9%) and color (45.4%) was observed. Further, GC-MS analysis of metabolites detected at different stages of treatment showed formation of degradation products of lignin and polycyclic aromatic compounds. Treatment efficiency was finally evaluated by the alkaline comet assay in HepG2 human hepato-carcinoma cells. The results indicated no statistically significant DNA damage at the end of the treatment, making the effluent suitable to be discharged conforming to the safety standards. PMID- 25113408 TI - Clinical inertia in individualising care for diabetes: is there time to do more in type 2 diabetes? AB - Clinical inertia is defined as the failure to establish appropriate targets and escalate treatment to achieve treatment goals. It accounts for a significant proportion of failure to achieve targets in the management of diabetes and contributes to up to 200,000 adverse diabetes- related outcomes per year. Despite a growing awareness of the phenomenon, and newer, better-tolerated agents for the control of diabetes, there has been little improvement over the last decade in the prevalence of clinical inertia. Although common-place in clinical practice, clinical inertia does not appear to affect clinical trials. There are lessons that may be translated from these randomised controlled trials to clinical practice, which that may improve the care for those with diabetes. Key amongst these interventions are good education, clear treatment strategy and more time for interaction between physician and patients, all of which appears to reduce clinical inertia as evidenced by the "placebo effect" of clinical trials. We plan to review here, the lessons that can be learnt from clinical trials and how these may translate to better care for people with diabetes. PMID- 25113407 TI - Fast and versatile fabrication of PMMA microchip electrophoretic devices by laser engraving. AB - This paper describes the effects of different modes and engraving parameters on the dimensions of microfluidic structures produced in PMMA using laser engraving. The engraving modes included raster and vector, while the explored engraving parameters included power, speed, frequency, resolution, line-width, and number of passes. Under the optimum conditions, the technique was applied to produce channels suitable for CE separations. Taking advantage of the possibility to cut through the substrates, the laser was also used to define solution reservoirs (buffer, sample, and waste) and a PDMS-based decoupler. The final device was used to perform the analysis of a model mixture of phenolic compounds within 200 s with baseline resolution. PMID- 25113410 TI - Alternative methods for toxicity assessments in fish: comparison of the fish embryo toxicity and the larval growth and survival tests in zebrafish and fathead minnows. AB - An increased demand for chemical toxicity evaluations has resulted in the need for alternative testing strategies that address animal welfare concerns. The fish embryo toxicity (FET) test developed for zebrafish (Danio rerio) is one such alternative, and the application of the FET test to other species such as the fathead minnow (Pimephales promelas) has been proposed. In the present study, the performances of the FET test and the larval growth and survival (LGS; a standard toxicity testing method) test in zebrafish and fathead minnows were evaluated. This required that testing methods for the fathead minnow FET and zebrafish LGS tests be harmonized with existing test methods and that the performance of these testing strategies be evaluated by comparing the median lethal concentrations of 2 reference toxicants, 3,4-dicholoraniline and ammonia, obtained via each of the test types. The results showed that procedures for the zebrafish FET test can be adapted and applied to the fathead minnow. Differences in test sensitivity were observed for 3,4-dicholoraniline but not ammonia; therefore, conclusions regarding which test types offer the least or most sensitivity could not be made. Overall, these results show that the fathead minnow FET test has potential as an alternative toxicity testing strategy and that further analysis with other toxicants is warranted in an effort to better characterize the sensitivity and feasibility of this testing strategy. PMID- 25113409 TI - Comparison of magnetic resonance imaging sequences for depicting the subthalamic nucleus for deep brain stimulation. AB - Electrodes are surgically implanted into the subthalamic nucleus (STN) of Parkinson's disease patients to provide deep brain stimulation. For ensuring correct positioning, the anatomic location of the STN must be determined preoperatively. Magnetic resonance imaging has been used for pinpointing the location of the STN. To identify the optimal imaging sequence for identifying the STN, we compared images produced with T2 star-weighted angiography (SWAN), gradient echo T2*-weighted imaging, and fast spin echo T2-weighted imaging in 6 healthy volunteers. Our comparison involved measurement of the contrast-to-noise ratio (CNR) for the STN and substantia nigra and a radiologist's interpretations of the images. Of the sequences examined, the CNR and qualitative scores were significantly higher on SWAN images than on other images (p < 0.01) for STN visualization. Kappa value (0.74) on SWAN images was the highest in three sequences for visualizing the STN. SWAN is the sequence best suited for identifying the STN at the present time. PMID- 25113411 TI - Term breech deliveries in the Netherlands: did the increased cesarean rate affect neonatal outcome? A population-based cohort study. AB - OBJECTIVE: The aim of this study was to evaluate the effect of the increased cesarean rate for term breech presentation on neonatal outcome. We also investigated whether the clinical case selection for vaginal delivery applied by Dutch obstetricians led to an optimization of neonatal outcome, or whether there is still room for improvement in terms of perinatal outcome. DESIGN: Retrospective cohort. SETTING: The Netherlands. POPULATION: Singleton term breech deliveries from 37+0 to 41+6 weeks, excluding fetuses with congenital malformations or antenatal death. METHOD: We used data from the Dutch national perinatal registry from 1999 up to 2007. MAIN OUTCOME MEASURES: Perinatal mortality and morbidity. RESULTS: We studied 58,320 women with a term breech delivery. There was an increase in the elective cesarean rate (from 24 to 60%). As a consequence, overall perinatal mortality decreased [1.3 0/00 vs. 0.7 0/00;odds ratio 0.51 (95% confidence interval 0.28-0.93)], whereas it remained stable in the planned vaginal birth group [1.7 0/00 vs. 1.6 0/00; odds ratio 0.96(95% confidence interval 0.52-1.76)]. The number of cesareans done to prevent one perinatal death was 338. CONCLUSIONS: Adjustment of the national guidelines after publication of the Term Breech Trial resulted in a shift towards elective cesarean and a decrease of perinatal mortality and morbidity among women delivering a child in breech at term. Still, 40% of these women attempt vaginal birth. The relative safety of an elective cesarean should be weighed against the consequences of a scarred uterus in future pregnancies. PMID- 25113412 TI - Giant enhancement of ferroelectric retention in BiFeO3 mixed-phase boundary. AB - A large enhancement of nanodomain retention is shown in the mixed-phase region of a strained BiFeO3 epitaxial film. The superior ferroelectric retention is attributed to a lower elastic-energy density at the phase boundaries, which act as periodic pinning centers for the domain wall motion. This study delivers a new pathway of incorporating an elastic-energy term to assist ferroelectric retention. PMID- 25113414 TI - Long-term sevelamer treatment lowers serum fibroblast growth factor 23 accompanied with increasing serum Klotho levels in chronic haemodialysis patients. AB - AIMS: Fibroblast growth factor 23 (FGF23) and Klotho are associated with vascular calcification and cardiovascular disease in dialysis patients. Sevelamer has been shown to reduce progression of vascular calcification. This study aimed to determine the long-term effect of sevelamer treatment on serum FGF23 and Klotho levels in chronic haemodialysis (HD) patients. METHODS: In the post-hoc analysis, we measured serum FGF23, Klotho and other biochemical factors (Ca, P, i-PTH, hsCRP, LDL-C) in 50 haemodialysis patients, who completed a 48-week, open-Label, controlled randomized parallel-group study. Twenty-three patients received sevelamer and 27 patients received calcium carbonate. RESULTS: After 48-week sevelamer treatment, there were significant changes with lower LDL-C (from 2.82 +/- 0.78 to 1.65 +/- 0.53 mmol/L, P = 0.000), lower FGF23 (from 2465.97 (2568.88) to 795.61 (1098.39), P = 0.000) and higher s-Klotho levels (from 189.35 (161.88) to 252.94 (517.80) pg/mL, P = 0.000). In calcium carbonate group, there were no significant changes of LDL-C and FGF23, but with a borderline significant increase of s-Klotho level (from 142.34 (265.24) to 188.57 (252.38) pg/mL, P = 0.054). Multivariate analysis showed that FGF23 decrement was associated with sevelamer treatment (beta = -0.277, P = 0.005), change of serum phosphate (beta = 0.609, P = 0.000) and calcium levels (beta = 0.635, P = 0.000). The increase of serum Klotho was associated with the decrease of serum phosphate (beta = 0.490, P = 0.019). CONCLUSION: Maintenance HD patients had lower serum FGF23 levels, accompanied with significantly increased serum Klotho levels, after 48-week sevelamer treatment. The FGF23 decrement was associated with sevelamer use, the change of serum phosphate and calcium levels. The serum Klotho increment was proportional to the phosphate-lowering power of the binders. PMID- 25113413 TI - Stress response signaling and virulence: insights from entomopathogenic fungi. AB - The Ascomycete fungal insect pathogens, Beauveria and Metarhizium spp. have emerged as model systems with which to probe diverse aspects of fungal growth, stress response, and pathogenesis. Due to the availability of genomic resources and the development of robust methods for genetic manipulation, the last 5 years have witnessed a rapid increase in the molecular characterization of genes and their pathways involved in stress response and signal transduction in these fungi. These studies have been performed mainly via characterization of gene deletion/knockout mutants and have included the targeting of general proteins involved in stress response and/or virulence, e.g. catalases, superoxide dismutases, and osmolyte balance maintenance enzymes, membrane proteins and signaling pathways including GPI anchored proteins and G-protein coupled membrane receptors, MAPK pathways, e.g. (i) the pheromone/nutrient sensing, Fus3/Kss1, (ii) the cell wall integrity, Mpk1, and (iii) the high osmolarity, Hog1, the PKA/adenyl cyclase pathway, and various downstream transcription factors, e.g. Msn2, CreA and Pac1. Here, we will discuss current research that strongly suggests extensive underlying contributions of these biochemical and signaling pathways to both abiotic stress response and virulence. PMID- 25113415 TI - Change in health status in long-term conditions over a one year period: a cohort survey using patient-reported outcome measures. AB - BACKGROUND: Enhancing quality of life for people with long-term conditions by monitoring patient-reported outcome measure scores is a key domain of health care policy. This study investigated the responsiveness of patient-reported outcome measures for long-term conditions. METHODS: A cohort survey was conducted in 33 primary care practices and 4485 patients (1334 asthma, 567 chronic obstructive pulmonary disease, 1121 diabetes, 525 epilepsy, 520 heart failure and 418 stroke) were sent a baseline survey containing a generic (EQ-5D) and a disease-specific measure. Baseline respondents were sent a follow-up after 1 year. Differences in scores for each long-term condition were assessed by paired t-tests. The relationship between scores and self-reported 'change in health' was assessed by analysis of variance. RESULTS: The baseline achieved a 38.4% response rate and the follow-up 71.5%. The only significant difference for the EQ-5D was found for the Visual Analogue Scale in heart failure between baseline and follow-up, and for change in health. Significant differences between baseline and follow-up scores were found on the disease-specific measures for 1 asthma dimension and 1 stroke dimension. No significant differences were found for other conditions. Significant differences between self-reported change in health and the disease specific measures were found for 4 asthma dimensions and 2 stroke dimensions. CONCLUSIONS: Few significant differences were found between the baseline and follow up or between 'change in health' and PROMs scores. This could be explained by the time frame of one year being too short for change to occur or by the PROMs not being responsive enough to change in a primary care sample. The latter is unlikely as the PROMs were in part chosen for their responsiveness to change. The baseline response rates may mean that the sample is not representative, and stable patients may have been more likely to participate. If PROMs are to be used routinely to monitor outcomes in LTCs, further research is needed to maximize response rates, to ensure that the PROMs used are reliable, valid and sensitive enough to detect change and that the time frame for data collection is appropriate. PMID- 25113416 TI - Study on the immune response to recombinant Hsp70 protein from Megalobrama amblycephala. AB - The expression of heat shock protein 70 (Hsp70) is induced in response to many factors including high temperature, infection, metal pollutants and toxic chemicals. In this study, Megalobrama amblycephala HSP70 promoter was cloned, and characteristic heat shock elements (HSEs) were identified in the promoter region. The recombinant M. amblycephala Hsp70 protein (rMaHsp70) was expressed and purified from Escherichia coli BL21 (DE3). To evaluate in vivo immune response of rMaHsp70, we administered intraperitoneal (IP) injection, and demonstrated that rMaHsp70 stimulated M. amblycephala immune activity by inducing the expression of HSP70, HIF-1alpha, HSC70, CXCR4b, TNF-alpha and IL-1beta mRNAs in liver, headkidney, spleen and gill, as well as SOD, glutathione, lysozyme and interferon alpha proteins in serum and liver. The effect of rMaHsp70 as adjuvant against Aeromonas hydrophila was assessed by injecting a mixed vaccine of rMaHsp70 and A. hydrophila (A. hydrophila/Hsp70) into M. amblycephala, and the relative percent survival (RPS) in the A. hydrophila/Hsp70 group was 75% compared to 50% in the A. hydrophila/PBS group. Furthermore, rMaHsp70 also promoted the proliferation and suppressed apoptosis in M. amblycephala fin cells (MAF) in a dose-dependent manner. Taken together, these results suggest that rMaHsp70 can induce organic immune response and improve environmental tolerance. PMID- 25113417 TI - Both habitual short sleepers and long sleepers are at greater risk of obesity: a population-based 10-year follow-up in women. AB - OBJECTIVE: To assess how change in sleep duration is related to subsequent obesity. METHODS: In this 10-year follow-up, 4903 non-pregnant participants answered a questionnaire on sleeping habits, obesity, and lifestyle factors (questions identical to baseline questionnaire). Habitual normal sleepers were defined as sleeping 6-9 h/night at both baseline and follow-up, whereas women sleeping <6 h/night or >=9 h/night at both occasions were defined as habitual short sleepers and habitual long sleepers, respectively. Logistic regression was used to analyze associations between changes in sleep duration, general obesity (body mass index >=30 kg/m(2)), weight gain (>=10 kg) and also, central obesity (waist circumference >=88 cm), and increase in waist circumference (>=10 cm) at follow-up. RESULTS: Among younger women (aged <40 years) both habitual short sleepers and habitual long sleepers had a higher prevalence of general (short: 31.3%, P < 0.0001; long: 38.1%, P = 0.01) and central obesity (short: 60.5%, P = 0.01; long: 82.4%, P = 0.01) compared with habitual normal sleepers (general obesity: 8.9%; central obesity: 35.9%) at follow-up. Younger women who were short sleepers at baseline but normal sleepers at the follow-up had a higher prevalence of both general (19.3%, P = 0.01) and central obesity (45.4%, P = 0.07) compared with habitual normal sleepers at follow-up. In adjusted analyses, both habitual short [adjusted odds ratio (aOR), 6.78; 95% confidence interval (CI), 2.71-17.0] and long (aOR, 4.64; 95% CI, 1.09-19.8) sleep durations were risk factors for general obesity in younger women. In younger women habitual long sleep duration was a risk factor also for central obesity (aOR, 6.05; 95% CI, 1.19-30.7) whereas habitual short sleep duration was not (aOR, 1.93; 95% CI, 0.87-4.81). Similar results were seen also for weight gain and increased waist circumference as dependent variables. In addition, decreased sleep duration from normal to short duration was a risk factor for both weight gain (aOR, 1.85; 95% CI, 1.14-3.02) and increased waist circumference (aOR, 1.84; 95% CI, 1.20-2.81). There were no associations between changes in sleep duration and any of the measures of obesity at the follow-up in women aged >40 years at baseline. CONCLUSION: In younger women, both habitual short and long sleep duration was a risk factor for obesity, whereas no such relationship was seen in older women. PMID- 25113418 TI - Quantifying the influence of safe road systems and legal licensing age on road mortality among young adolescents: steps towards system thinking. AB - Based on existing literature, a system thinking approach was used to set up a conceptual model on the interrelationships among the components influencing adolescent road mortality, distinguishing between components at the individual level and at the system level. At the individual level the role of risk behaviour (sometimes deliberate and sometimes from inexperience or other non-deliberate causes) in adolescent road mortality is well documented. However, little is known about the extent to which the 'road system' itself may also have an impact on younger adolescents' road mortality. This, by providing a safe or unsafe road environment for all road users (System-induced exposure) and by allowing access to high-risk vehicles at a young or older age through the legal licensing age. This study seeks to explore these relationships by analysing the extent to which the road mortality of 10 to 17 year olds in various jurisdictions can be predicted from the System-induced Exposure (SiE) in a jurisdiction and from its legal licensing age to drive motor vehicles. SiE was operationalized as the number of road fatalities per 10(5) inhabitants/all ages together, but excluding the 10 to 17 year olds. Data on road fatalities during the years 2001 through 2008 were obtained from the OECD International Road Traffic Accident Database (IRTAD) and from the USA NHTSA's Fatality Analysis Reporting System (FARS) database for 29 early and 10 late licensing jurisdictions. Linear mixed models were fitted with annual 'Adolescent road mortality per capita' for 2001 through 2008 as the dependent variable, and time-dependent 'SiE' and time-independent 'Licensing system' as predictor variables. To control for different levels of motorisation, the time-dependent variable 'Annual per capita vehicle distance travelled' was used as a covariate. Licensing system of a jurisdiction was entered as a categorical predictor variable with late licensing countries as a baseline group. The study found support for the protective effects of SiE on adolescent safety. If SiE increased by one unit, the mortality rate of 10 to 17 year olds increased by 0.487 units. No support was found for a protective effect of late licensing for this age group. Thus, compared to young adolescents who are allowed to drive motor vehicles in early licensing jurisdictions, late licensing does not provide extra protection for pre-license adolescents. This finding is probably the result of the high risks associated with alternative transport modes, such as moped riding and bicycling. Also, the fact that the study only included risks to young adolescents themselves and did not include the risks they might pose to other road users and passengers may have contributed to this finding, because such risks are greater when driving a motor vehicle than riding a moped or a bicycle. Therefore, to advance our understanding of the impact of licensing systems, more study is needed into the benefits of early or late licensing, thereby considering these wider effects as well. PMID- 25113419 TI - [Alcohol consumption in patients with psychiatric disorders: assessment and treatment]. AB - Alcohol consumption in France exceeds the European average (12.7L of pure alcohol/habitant/year in 2009 for an average of 12.5 L). This consumption has a major professional, social and health impact on the individuals and their families. The cost of such, estimated in Europe to be of 155.8 billion Euros in 2010, is the highest among the central nervous system diseases in Europe, far higher than that of depression or dementia. Patients suffering from psychiatric disorders are more frequently affected by problems related to alcohol use than the general population. They are also more vulnerable to the immediate and subsequent consequences of their consumption. The alcohol related disorders that are often accompanied by risk taking and other addictive behaviour require a global assessment of the addiction, with and without substance, and of the complications. These have a strong impact on risk taking, compliance with care, and the morbidity of somatic and psychiatric disorders, as well as access to optimal care and the life span of patients suffering from psychiatric disorders. The development of addictology care, with integrative treatment programs, is recommended in response to these public health issues. Nevertheless, specific addictology practices and partners with addictology care structures are still scarcely developed in psychiatry. Firstly, it would be necessary to set up such integrated treatments through the systematisation of an "addictology" checkup on admission, a global assessment of addictive behaviour and cognitive disorders, using pragmatic tools that are user-friendly for the care teams, maintain the reduction in risk taking, and apply prescriptions for addiction to psychotropic treatments, in liaison with the referring general practitioner. As early as possible, accompanied by specific training in addictology for the psychiatrists and the mental health nursing teams, such care could be enhanced by the development of liaison and advanced psychiatric consultation teams, specialised in addictology, together with the installation of a addictology care network in supplementary psychiatry of levels 1, 2 and 3 in addictology. This network of specific care would notably permit the integrated management of patients suffering from acute psychiatric disorders or requiring care under constraint. More specific care networks for particular problems (maternity issues, adolescence, HIV and hepatitis, cognitive disorders...) and programs of therapeutic education could reinforce this proposal within a protocol of care that should be legible, coherent and coordinated. The psychiatrist and the addictologist must therefore learn to work together over and above the dogmatic boundaries and positioning in a constructive and efficient partnership, beneficial for the patient. PMID- 25113420 TI - Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti Ro52 antibodies in patients with autoimmune hepatitis. AB - BACKGROUND & AIMS: Antibodies (Abs) to soluble liver antigen/liver pancreas (anti SLA/LP) are considered markers of worse prognosis and outcome in patients with autoimmune hepatitis (AIH) although this assumption has recently been attributed to their frequent co-expression with Abs against Ro52 (anti-Ro52). To assess the clinical significance of anti-SLA/LP Abs alone or in combination with anti-Ro52 in AIH patients and determine the immunodominant Ro52 epitopes according to the anti-SLA/LP status. METHODS: Twenty-three anti-SLA/LP-positive and 106 anti SLA/LP-negative AIH patients were included. Anti-SLA/LP were determined by ELISA using recombinant antigen, and confirmed by immunoblot using cytosolic rat liver fraction or HuH-7 extract. Anti-Ro52 Abs were determined by ELISA using recombinant antigen. Epitope mapping was assessed by ELISA using overlapping peptides covering the whole Ro52 protein in 26 AIH patients and 12 patients with Sjogren's syndrome. RESULTS: Anti-SLA/LP positivity was not associated with the clinical, laboratory or histological characteristics of AIH patients. Treatment response, corticosteroid withdrawal, relapse after stopping treatment and outcome, were not associated with the presence of anti-SLA/LP, anti-Ro52 or double reactivity. Moreover, Ro52 epitope mapping revealed new epitopes unique for AIH and independent from anti-SLA/LP positivity. CONCLUSIONS: Neither anti SLA/LP nor anti-Ro52 Abs or their combination could specify a distinct group of AIH patients in terms of clinical characteristics, treatment response and outcome. Further studies are needed to clarify whether the newly discovered immunodominant epitopes of Ro52 antigen which were associated specifically with AIH have any clinical or pathogenetic significance in AIH. PMID- 25113421 TI - GlycoMaster DB: software to assist the automated identification of N-linked glycopeptides by tandem mass spectrometry. AB - Glycosylation is one of the most commonly observed post-translational modifications (PTMs) in eukaryotes. It is believed that more than 50% eukaryotic proteins are glycosylated. To reveal the biological functions of protein-linked glycans involved in numerous biological processes, the high-throughput identification of both glycoproteins and the attached glycan structures becomes fundamentally important. Tandem mass spectrometry (MS/MS) is an effective method for glycoproteomic analysis because of its high sensitivity and selectivity. Two experimental approaches exist to obtain MS/MS spectral data of glycopeptides. One consists of isolating glycans from glycopeptides and generating MS/MS spectra of the glycans and peptides separately. The other approach produces spectra directly from intact glycopeptides. The latter approach has the advantage of retaining the glycosylation site information. However, the spectral data cannot be readily analyzed because of the lack of software specifically designed for the identification of intact glycopeptides. To address this need, we developed a novel software tool, GlycoMaster DB, to assist the automated and high-throughput identification of intact N-linked glycopeptides from MS/MS spectra. The software simultaneously searches a protein sequence database and a glycan structure database to find the best pair of peptide and glycan for each input spectrum. GlycoMaster DB can analyze mass spectral data produced with HCD/ETD mixed fragmentation, where HCD spectra are used to identify glycans and ETD spectra are used to determine peptide sequences. When only HCD spectra are available, GlycoMaster DB can still help to identify the glycans, and a list of possible peptide sequences are reported according to the accurate precursor mass and the N linked glycopeptide sequon. GlycoMaster DB is freely accessible at http://www novo.cs.uwaterloo.ca:8080/GlycoMasterDB . PMID- 25113423 TI - Fires in Indian hospitals: root cause analysis and recommendations for their prevention. AB - There is an increase in the incidence of intraoperative fire in Indian hospitals. It is hypothesized that oxygen (O2) enrichment of air, is primarily responsible for most of the fires, particularly in intensive care units. As the amount of ignition energy needed to initiate fire reduces in the presence of higher O2 concentration, any heat or spark, may be the source of ignition when the air is O2-rich. The split air conditioner is the source of many such fires in the ICU, neonatal intensive care unit (NICU), and operating room (OR), though several other types of equipment used in hospitals have similar vulnerability. Indian hospitals need to make several changes in the arrangement of equipment and practice of handling O2 gas, as well as create awareness among hospital staff, doctors, and administrators. Recommendations for changes in system practice, which are in conformity with the National Fire Protection Association USA, are likely to be applicable in preventing fires at hospitals in all developing countries of the world with warm climates. PMID- 25113422 TI - Quantification of clonal circulating plasma cells in relapsed multiple myeloma. AB - The presence of clonal circulating plasma cells (cPCs) remains a marker of high risk disease in newly diagnosed multiple myeloma (MM) patients. However, its prognostic utility in MM patients with previously treated disease is unknown. We studied 647 consecutive patients with previously treated MM seen at the Mayo Clinic, Rochester who had their peripheral blood evaluated for cPCs by multi parameter flow cytometry. Of these patients, 145 had actively relapsing disease while the remaining 502 had disease that was in a plateau and included 68 patients in complete remission (CR) and 434 patients with stable disease. Patients with actively relapsing disease were more likely to have clonal cPCs than those in a plateau (P < 0.001). None of the patients in CR had any clonal cPCs detected. Among patients whose disease was in a plateau, the presence of clonal cPCs predicted for a worse median survival (22 months vs. not reached; P = 0.004). Among actively relapsing patients, the presence of >=100 cPCs predicted for a worse survival after flow cytometry analysis (12 months vs. 33 months; P < 0.001). Future studies are needed to determine the role of these findings in developing a risk-adapted treatment approach in MM patients with actively relapsing disease. PMID- 25113424 TI - Retrospective review of predisposing factors for intraoperative pressure ulcer development. AB - STUDY OBJECTIVE: To evaluate the comorbidities and surgical factors involved in the genesis of intraoperative pressure ulcers. DESIGN: Retrospective chart review. SETTING: Anesthesiology department of a university medical center. MEASUREMENTS: The charts of 222 patients with varying illness, who underwent an operation of at least two hours' duration, were analyzed retrospectively. Data on surgery type, case length, comorbidities, intraoperative surgical position, and area of ulceration were recorded. MAIN RESULTS: Risk factors for intraoperative pressure ulcer development include surgical times of 4 hours or longer; comorbidities affecting tissue perfusion (namely, diabetes, hypertension, and nonspecific cardiac issues); supine placement during surgery; and abdominal, noncardiac thoracic, and orthopedic operations. Regions of the body most at risk for ulceration include the coccygeal/sacral region, the buttocks, genitalia, and heels. CONCLUSIONS: Pressure ulcers are a costly, debilitating, and avoidable complication of surgery. PMID- 25113425 TI - Which nostril should be used for nasotracheal intubation: the right or left? A randomized clinical trial. AB - STUDY OBJECTIVE: To determine which nostril is more suitable for nasotracheal intubation in patients with normal patency of both nostrils. DESIGN: Prospective, randomized clinical trial. SETTING: Operating room of a university medical center. PATIENTS: 191 ASA physical status 1 and 2 patients scheduled for elective oral surgery requiring general anesthesia with nasotracheal intubation. INTERVENTIONS: Patients were randomized to two groups to undergo nasotracheal intubation through the right nostril (Group R; n = 96) or the left nostril (n = 95). Standard traditional nasotracheal intubation was performed using the Macintosh laryngoscope. Tube rotation was attempted for alignment toward the glottis, and Magill forceps were then used to assist intubation, as necessary. MEASUREMENTS: Epistaxis was inspected in the pharynx after the tube tip was passed through the nasal cavity and 15 minutes after nasotracheal intubation was completed. Intubation time was the interval between when the anesthesiologist opened the patient's mouth with the cross finger maneuver and when the tube was connected to the anesthetic circuit after nasotracheal completion. MAIN RESULTS: The frequency of epistaxis was significantly lower in Group R than Group L (P = 0.0006). Although there was no significant difference in nasal passage time between two groups, the intubation time in Group R (24.5 +/- 9.4 sec) was shorter than in Group L (30.5 +/- 15.6 sec; P = 0.0015). CONCLUSION: Nasal intubation via the right nostril is more safely performed than with the left nostril. Because of less epistaxis and faster intubation. PMID- 25113426 TI - The effects of physical and geochemical heterogeneities on hydro-geochemical transport and effective reaction rates. AB - The role of coupled physical and geochemical heterogeneities in hydro-geochemical transport is investigated by simulating three-dimensional transport in a heterogeneous system with kinetic mineral reactions. Ensembles of 100 physically heterogeneous realizations were simulated for three geochemical conditions: 1) spatially homogeneous reactive mineral surface area, 2) reactive surface area positively correlated to hydraulic heterogeneity, and 3) reactive surface area negatively correlated to hydraulic heterogeneity. Groundwater chemistry and the corresponding effective reaction rates were calculated at three transverse planes to quantify differences in plume evolution due to heterogeneity in mineral reaction rates and solute residence time (tau). The model is based on a hypothetical CO2 intrusion into groundwater from a carbon capture utilization and storage (CCUS) operation where CO2 dissolution and formation of carbonic acid created geochemical dis-equilibrium between fluids and the mineral galena that resulted in increased aqueous lead (Pb(2+)) concentrations. Calcite dissolution buffered the pH change and created conditions of galena oversaturation, which then reduced lead concentrations along the flow path. Near the leak kinetic geochemical reactions control the release of solutes into the fluid, but further along the flow path mineral solubility controls solute concentrations. Simulation results demonstrate the impact of heterogeneous distribution of geochemical reactive surface area in coordination with physical heterogeneity on the effective reaction rate (Krxn,eff) and Pb(2+) concentrations within the plume. Dissimilarities between ensemble Pb(2+) concentration and Krxn,eff are attributed to how geochemical heterogeneity affects the time (taueq) and therefore advection distance (Leq) required for the system to re-establish geochemical equilibrium. Only after geochemical equilibrium is re-established, Krxn,eff and Pb(2+) concentrations are the same for all three geochemical conditions. Correlation between reactive surface area and hydraulic conductivity, either positive or negative, results in variation in taueq and Leq. PMID- 25113427 TI - The external use of comfrey: a practitioner survey. AB - AIM: The survey aimed to assess how often and in what ways herbal practitioners use comfrey (Symphytum officinale L.) externally in everyday practice. METHODS: A 2-sided A4 survey was sent to all UK members of the National Institute of Medical Herbalists, the College of Practitioners of Phytotherapy and the Association of Master Herbalists with viable practice addresses (n = 598). RESULTS: 239 herbalists responded, of whom 179 (75%) reported regularly using comfrey, in 15% of their consultations. It was most commonly prescribed as a cream for tendon, ligament and muscle problems, for fractures, and for wounds, the indications for which it was also perceived to be most effective. Comfrey was rated least effective for haemorrhoids, varicose veins and boils and was considered to carry the greatest risk when prescribed for ulcers, wounds and boils. CONCLUSION: Practitioner experience suggests that comfrey can be used safely and effectively externally for certain indications. PMID- 25113428 TI - Long-term inverse modeling of Chinese CO emission from satellite observations. AB - Carbon monoxide (CO) emissions in China in 2005-2010 were estimated by inversion, using the Green's function method from vertical CO profiles derived from MOPITT Version 5 satellite data and a tagged CO simulation, and validated with independent in situ observations from the World Data Centre for Greenhouse Gases. Modeling with a posteriori emission successfully reproduced CO outflow from the continent to the East China Sea, Sea of Japan, and Japanese islands during winter and spring, and compensated for underestimates in central and eastern China in summer. A posteriori emissions showed large seasonal variations in which December and March emissions were on average 23% larger than August emissions, consistent with other studies. Estimated Chinese CO emissions were 184.4, 173.1, 184.6, 158.4, 157.4, and 157.3 Tg/year for 2005-2010, respectively. The decrease after 2007 is partly attributed to Chinese socioeconomic conditions and improved combustion efficiency. PMID- 25113429 TI - Crystallization and its effect on the mechanical properties of a medium chain length polyhydroxyalkanoate. AB - Medium chain length polyhydroxyalkanoates (mcl-PHAs) could play a role in the growing demand for highly elastic and biodegradable materials in the medical field. In this study, a poly(3-hydroxyoctanoate-co-3-hydroxyhexanoate) (P(3HO-co 3HH)) was first fully characterized in terms of molecular weight, microstructural chain parameters and chemical structure by means of gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR). As determined by NMR, the synthesized polymer contained 94.3% and 5.7% molar content of 3-hydroxyoctanoate and 3-hydroxyhexanoate, respectively. Since mechanical properties are closely related to thermal history, the effect of crystallization on tensile properties was also investigated in the present study. Three crystallization temperatures were selected (0, 23 and 37 degrees C), the conclusion reached is that the maximum crystallization rate for this copolymer was achieved at 0 degrees C. On the other hand, evolution of tensile properties of P(3HO-co-3HH) films stored at room temperature demonstrated that, as crystallization occurred toward the equilibrium state, the polymer underwent a stiffening process. In this sense, secant modulus and tensile strength increased respectively from 8.3 +/- 1.0 MPa and 6.4 +/- 0.8 MPa after 1 day stored at room temperature to 36.2 +/- 3.3 MPa and 16.3 +/- 2.1 MPa after 16 weeks. PMID- 25113430 TI - Targeted SLNs for management of HIV-1 associated dementia. AB - CONTEXT: HIV-1 associated dementia (HAD) is an evolving disease in the category of neurological disorders. OBJECTIVE: Nifedipine-loaded solid lipid nanoparticles (SLNs) were developed and coated with Tween 80 to facilitate enhanced brain drug delivery for the treatment of HAD. MATERIALS AND METHODS: SLNs were prepared using solvent injection method. Lipids consisted of tristearin, hydrogenated soya phosphatidylcholine (HSPC) (1.5:1 w/w). Nifedipine was model drug in this study. Tween 80 (0.5% v/v) was taken as key modulator. SLNs were characterized for particle shape, size, zeta potential, entrapment efficiency, in vitro drug release, DNA fragmentation, cytotoxicity potential and in vivo studies. RESULTS: The SLNs (plain and coated) were found to be in nanometric in size (~120 nm) with more than 70% entrapment efficiency. In vitro drug release profile reflected sustained release up to 48 h. Tween 80-coated SLNs showed higher percentage of DNA fragmentation in vitro and enhanced cell viability in sulforhodamine assay (rat cortical cells) as compared to plain drug and uncoated SLNs due to facilitated uptake of SLNs and reversal of P-gp efflux by virtue of Tween 80. Biodistribution study performed on vital organs, i.e. brain, heart, liver, spleen, lungs and kidney showed increased accumulation of Tween 80-coated SLNs in the brain. DISCUSSION AND CONCLUSION: Tween 80 enhanced localization of SLNs in the brain as compared to uncoated SLNs. This approach can be employed effectively to transport chemotherapeutics across the BBB for management of HIV-1 associated dementia and other ailments. PMID- 25113431 TI - Development of ocular drug delivery systems using molecularly imprinted soft contact lenses. AB - Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug loading capacity, and the release properties of molecularly imprinted hydrogels. PMID- 25113432 TI - Enhancement of the oral bioavailability of breviscapine by nanoemulsions drug delivery system. AB - Aim to design an effective breviscapine nanoscale drug delivery system to realize the improvement of its oral bioavailability. Based on the investigations of the stabilities in the gastrointestinal tract (GIT), permeation and efflux across the cell membrane, the breviscapine nanoemulsion (NE) was formulated and evaluated in vitro and in vivo. The globule size and polydispersity index of the NE was 45.6 nm and 0.105, and the efficient encapsulation was 95.2%. In vitro, the drug release from NEs in pH 6.8 PBS fit to the first-order kinetics. The Caco-2 cell transport experiments showed that the breviscapine NE facilitated the improvement of the apparent permeability coefficient (Papp) from the apical side to basilar side compared with the free drug. In vivo, the relative bioavailability of breviscapine NE reached to 249.7%. All the studies implicated that the NE carrier contributed to the enhancement of the oral absorption of breviscapine due to the improved stability and permeation in the GIT. The nanoemulsions technology is better for the poor permeable and unstable active agents in GIT as well as helps the industrial scale process. PMID- 25113435 TI - Synthesis and characterization of inorganic-organic hybrid gallium selenides. AB - Two semiconducting hybrid gallium selenides, [Ga6Se9(C6H14N2)4][H2O] (1) and [C6H14N2][Ga4Se6(C6H14N2)2] (2), were prepared using a solvothermal method in the presence of 1,2-diaminocyclohexane (1,2-DACH). Both materials consist of neutral inorganic layers, in which 1,2-DACH is covalently bonded to gallium. In 1, the organic amine acts as a monodentate and a bidentate ligand, while in 2, bidentate and uncoordinated 1,2-DACH molecules coexist. PMID- 25113436 TI - Optical coherence tomography-based retinal vessel analysis for the evaluation of hypertensive vasculopathy. AB - PURPOSE: Evaluation of retinal vessels in cardiovascular disease traditionally relies upon funduscopy, but more recently digital photo analysis has expanded the spectrum. As spectral domain optical coherence tomography (OCT) allows an in-vivo assessment of retinal tissue and its vessels on a histological scale, our study aimed at using this tool for the analysis of the retinal vasculature. METHODS: Circumferential peripapillary OCT scans (3DOCT-2000; Topcon Inc., Tokyo, Japan), with centration on the optic nerve head, were taken from 20 eyes (20 participants) with normal blood pressure and 20 eyes (20 participants) with arterial hypertension above 120 mmHg (mean blood pressure). The diameter of all vessels intersecting the scan line was measured in the OCT and used to calculate central vessel equivalents, and the A/V ratios were calculated. Bland-Altman analysis was performed to evaluate reliability. Correlation coefficients were determined for reliability of the method as well as with the individual mean arterial blood pressures. RESULTS: Forty eyes (40 participants) were included in the study. Mean arterial blood pressure was 96+/-4 mmHg in the control group and 132+/-7 mmHg in the hypertonic group. Mean A/V ratio as determined from OCT scans was 0.82+/-0.13 (normotonic) versus 0.62+/-0.11 (hypertonic). A Pearson's correlation coefficient of 0.67 (p<0.001) was determined between A/V ratio and blood pressure. CONCLUSIONS: Our results highlight the feasibility of retinal vessel measurements in spectral domain OCT. A relation between mean arterial blood pressure and OCT-based A/V ratio was established. Further research will elucidate influencing factors and provide a broader basis for therapeutic approaches. PMID- 25113434 TI - A meta-analysis of the relationship between trait mindfulness and substance use behaviors. AB - BACKGROUND: The relationship between trait mindfulness and substance use behaviors has been inconsistent across studies. The current meta-analysis aimed at quantifying the magnitude of this relationship, and at determining how this relationship varies in context of (1) mindfulness facets, (2) substance type, (3) sample characteristics, and (4) substance use severity. METHODS: Using electronic databases, the literature search yielded 303 articles, but only 39 articles met inclusion criteria to be included in this meta-analysis. The relationship was quantified as a Pearson's r correlation coefficient for all studies. RESULTS: Findings indicated a small, negative, and significant trait mindfulness-substance use behaviors relationship (r=-0.13). This relationship varied across substance type, clinical status of the sample, and substance use severity. Mindfulness facet was not a significant moderator; however, only particular facets (e.g., acting with awareness, non-judgment, and non-reactivity) were consistently associated with substance use behaviors. CONCLUSIONS: This meta-analysis quantified the trait mindfulness-substance use behaviors relationship, which can be used as future effect size estimates. Findings also indicated that the trait mindfulness-substance use behaviors relationship was more robust: (1) for alcohol and tobacco use compared to marijuana use behaviors; (2) for problematic compared to non-problematic substance use behaviors; and (3) with inpatient compared to outpatient and non-clinical samples. Further work should continue to examine if acting with awareness, non-judgment, and non-reactivity mindfulness facets are more robustly associated with substance use behaviors. Failure to consider these factors, or collapsing across these factors, could explain the smaller or inconsistently reported associations across previous studies. PMID- 25113437 TI - Dehydrative cross-coupling reactions of allylic alcohols with olefins. AB - The direct dehydrative activation of allylic alcohols and subsequent cross coupling with alkenes by using palladium catalyst containing a phosphoramidite ligand is described. The activation of the allyl alcohol does not require stoichiometric additives, thus allowing clean, waste-free reactions. The scope is demonstrated by application of the protocol to a series allylic alcohols and vinyl arenes, leading to variety of 1,4-diene products. Based on kinetic studies, a mechanism is proposed that involves a palladium hydride species that activates the allyl alcohol to form the allyl intermediate. PMID- 25113438 TI - Factors that characterize bone health with aging in healthy postmenopausal women. AB - The exponential increase in the incidence of fragility fractures in older people is attributed to attenuation of both bone strength and neuromuscular function. Decrease in bone mineral density (BMD) does not entirely explain this increase. The objective of this study is to investigate the effect of age on various parameters related to bone health with aging, and to identify combinations of factors that collectively express the bone metabolic state in healthy postmenopausal women. Height, weight, and grip strength were measured in 135 healthy postmenopausal volunteer women. Hip BMD, biomechanical indices derived from quantitative computed tomography (QCT), cross-sectional areas of muscle and fat of the proximal thigh, and various biochemical markers of bone metabolism were measured. A smaller group of factors explanatory for bone health was identified using factor analysis and each was newly named. As a result, the factors bone mass, bone turnover, bone structure, and muscle strength had the greatest explanatory power for assessing the bone health of healthy postmenopausal women. Whereas dual X-ray absorptiometry parameters only loaded on the factor bone mass, QCT parameters loaded on both the factors bone mass and bone structure. Most bone turnover markers loaded on the factor bone turnover, but deoxypyridinoline loaded on both bone turnover and muscle strength. Age was negatively correlated with bone mass (r = -0.49, p < 0.001) and muscle strength (r = -0.67, p < 0.001). We conclude that aging is associated as much with muscle weakening as with low BMD. More attention should be paid to the effects of muscle weakening during aging in assessments of bone health. PMID- 25113439 TI - Regulatory T cells with CD62L or TNFR2 expression in young type 1 diabetic patients: relation to inflammation, glycemic control and micro-vascular complications. AB - BACKGROUND: Alteration of regulatory T cells (Tregs) may contribute to ineffective suppression of proinflammatory cytokines in type 1 diabetes. AIM: We determined the percentage of Tregs expressing CD62L or tumor necrosis factor receptor type 2 (TNFR2) in 70 young type 1 diabetic patients compared with 30 controls and assessed their relation to inflammation, glycemic control and micro vascular complications. METHODS: High-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) were assessed with flow cytometric analysis of Tregs, Tregs expressing CD62L or TNFR2. RESULTS: The percentage of CD4(+)CD25(high) T cells and CD4(+)CD25(high)CD62L(high) cells were significantly decreased while CD4(+)CD25(high)TNFR2(+) T cells were elevated in patients with micro-vascular complications than those without and controls (p<0.001). ROC curve revealed that the cutoff values of Tregs, Tregs expressing CD62L and Tregs expressing TNFR2 (7.46%, 24.2% and 91.9%, respectively) could detect micro-vascular complications. Significant negative correlations were observed between Tregs expressing CD62L and disease duration, FBG, HbA1c, urinary albumin excretion and hs-CRP, whereas, positive correlations were found between Tregs expressing TNFR2 and these variables (p<0.05). TNF-alpha was significantly increased while IL-10 was decreased among patients with micro-vascular complications than those without (p<0.05). CONCLUSIONS: Alteration in the frequency of Tregs and Tregs expressing CD62L or TNFR2 in type 1 diabetes is associated with increased inflammation, poor glycemic control and risk of micro-vascular complications. PMID- 25113441 TI - A two-hybrid screen identifies an unconventional role for the intermediate filament peripherin in regulating the subcellular distribution of the SNAP25 interacting protein, SIP30. AB - Peripherin is a type III intermediate filament protein, the expression of which is associated with the acquisition and maintenance of a terminally differentiated neuronal phenotype. Peripherin up-regulation occurs during acute neuronal injury and in degenerating motor neurons of amyotrophic lateral sclerosis. The functional role(s) of peripherin during normal, injurious, and disease conditions remains unknown, but may be related to differential expression of spliced isoforms. To better understand peripherin function, we performed a yeast two hybrid screen on a mouse brain cDNA library using an assembly incompetent peripherin isoform, Per-61, as bait. We identified new peripherin interactors with roles in vesicular trafficking, signal transduction, DNA/RNA processing, protein folding, and mitochondrial metabolism. We focused on the interaction of Per-61 and the constitutive isoform, Per-58, with SNAP25 interacting protein 30 (SIP30), a neuronal protein involved in SNAP receptor-dependent exocytosis. We found that peripherin and SIP30 interacted through coiled-coil domains and colocalized in cytoplasmic aggregates in SW13vim(-) cells. Interestingly, Per-61 and Per-58 differentially altered the subcellular distribution of SIP30 and SNAP25 in primary motor neurons. Our findings suggest a novel role of peripherin in vesicle trafficking. PMID- 25113440 TI - Mutational and functional analysis of the tumor-suppressor PTPRD in human melanoma. AB - Protein tyrosine phosphatases (PTPs) tightly regulate tyrosine phosphorylation essential for cell growth, adhesion, migration, and survival. We performed a mutational analysis of the PTP gene family in cutaneous metastatic melanoma and identified 23 phosphatase genes harboring somatic mutations. Among these, receptor-type tyrosine-protein phosphatase delta (PTPRD) was one of the most highly mutated genes, harboring 17 somatic mutations in 79 samples, a prevalence of 21.5%. Functional evaluation of six PTPRD mutations revealed enhanced anchorage-dependent and anchorage-independent growth. Interestingly, melanoma cells expressing mutant PTPRD were significantly more migratory than cells expressing wild-type PTPRD or vector alone, indicating a novel gain-of-function associated with mutant PTPRD. To understand the molecular mechanisms of PTPRD mutations, we searched for its binding partners by converting the active PTPRD enzyme into a "substrate trap" form. Using mass spectrometry and coimmunoprecipitation, we report desmoplakin, a desmosomal protein that is implicated in cell-cell adhesion, as a novel PTPRD substrate. Further analysis showed reduced phosphatase activity of mutant PTPRD against desmoplakin. Our findings identify an essential signaling cascade that is disrupted in melanoma. Moreover, because PTPRD is also mutated in glioblastomas and adenocarcinoma of the colon and lung, our data might be applicable to a large number of human cancers. PMID- 25113442 TI - Ophthalmologic impairment during adulthood in central congenital hypoventilation syndrome: a longitudinal cohort analysis of nine patients. AB - BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare dysgenetic form of neurocristopathy associated with dysfunction of the autonomic nervous system. Ophthalmologic abnormalities are reported in CCHS children, and range from pupillary and iris abnormalities to ptosis, strabismus and convergence deficiency. Since earlier CCHS diagnosis and multidisciplinary management, combined with improved ventilatory support techniques, the lifespan of children with CCHS has been considerably lengthened. The oldest of them have now reached adult age and we report in this study the results of their ophthalmologic examination. MATERIALS AND METHODS: Nine CCHS adult patients were prospectively included during a 14-month period. Each patient underwent complete ophthalmologic examination, static pupillometry with scotopic and photopic pupillary diameter (PD) measures, Humphrey 24-2 visual field analysis, macular OCT and complete orthoptic assessment including a Hess-Lancaster test. RESULTS: Ophthalmologic abnormalities were found in six of the nine patients (66%). The main features were strabismus in six patients (66%). Four patients (44%) displayed abnormal pupillary function, with a decrease in average scotopic PD (3.8 +/- 1.4 mm), average photopic PD (3.5 +/- 1.2 mm), and average percentage of pupillary constriction (7.6 +/- 8.5%). Three patients (33%) exhibited iris abnormalities such as iris atrophy, smooth iris surface and atrophic sphincter. CONCLUSION: This study allowed the description of ophthalmologic abnormalities occurring in CCHS in a series of adult patients, thus improving current knowledge of the disease. The prevalence of pupillary and iris lesions were lower than those observed in a series of children, suggesting that they could be considered as systemic disease severity markers. PMID- 25113445 TI - Lessons from crop plants struggling with salinity. AB - Salinity is a persistent problem, causing important losses in irrigated agriculture. According to global climate change prediction models, salinity is expected to expand in the near future. Although intensive studies have been conducted on the mechanisms by which plants cope with saline conditions, the multi-component nature of salt stress tolerance has rendered most plant breeding efforts to improve the plant's response to salinity unsuccessful. This occurs despite the extensive genetic diversity shown by higher plants for salt tolerance and the similar mechanisms found in salt-sensitive and salt-tolerant genotypes in response to the presence of excess of salts in the growth media. On the other hand, there is an urge to increase crop yield to the maximum to cope with the growing world population demands for food and fuel. Here, we examine some major elements and signaling mechanisms involved in the plant's response to salinity following the pathway of salt-footprints from the soil environment to leaf. Some of the possible contrasting determinants for a better-balanced resource allocation between salt tolerance and plant growth and yield are considered. PMID- 25113446 TI - Mechanistic insights on the responses of plant and ecosystem gas exchange to global environmental change: lessons from Biosphere 2. AB - Scaling up leaf processes to canopy/ecosystem level fluxes is critical for examining feedbacks between vegetation and climate. Collectively, studies from Biosphere 2 Laboratory have provided important insight of leaf-to-ecosystem investigations of multiple environmental parameters that were not before possible in enclosed or field studies. B2L has been a testing lab for the applicability of new technologies such as spectral approaches to detect spatial and temporal changes in photosynthesis within canopies, or for the development of cavity ring down isotope applications for ecosystem evapotranspiration. Short and long term changes in atmospheric CO2, drought or temperature allowed for intensive investigation of the interactions between photosynthesis and leaf, soil and ecosystem respiration. Experiments conducted in the rainforest biome have provided some of the most comprehensive dataset to date on the effects of climate change variables on tropical ecosystems. Results from these studies have been later corroborated in natural rainforest ecosystems and have improved the predictive capabilities of models that now show increased resilience of tropics to climate change. Studies of temperature and CO2 effects on ecosystem respiration and its leaf and soil components have helped reconsider the use of simple first-order kinetics for characterizing respiration in models. The B2L also provided opportunities to quantify the rhizosphere priming effect, or establish the relationships between net primary productivity, atmospheric CO2 and isoprene emissions. PMID- 25113443 TI - Novel C8orf37 Mutations in Patients with Early-onset Retinal Dystrophy, Macular Atrophy, Cataracts, and High Myopia. AB - PURPOSE: More than 50 genes are reported as causative genes of autosomal recessive (ar) retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). It is challenging to identify causative mutations for arRP and arCRD. The purpose of the present study was to investigate clinical and genetic features of two siblings with early-onset retinal dystrophy. METHODS: Whole-exome sequencing was conducted for the two affected siblings and their unaffected brother and mother from a Japanese family. We performed complete ophthalmic examinations, including visual acuity, funduscopy, visual-field testing, electroretinography and optical coherence tomography. RESULTS: Whole-exome sequencing analysis identified novel compound heterozygous mutations, a splice site mutation (c.374 + 2T > C in intron 4) and a deletion mutation (c.575delC [p.T192MfsX28] in exon 6) of chromosome 8 open reading frame 37 (C8orf37) gene, which encodes a ciliary protein, in both patients. The mother carried the truncating mutation, and the brother carried neither mutation. Ophthalmic examinations revealed diffuse retinal degeneration, macular atrophy, non-recordable electroretinography responses, cataracts, and high myopia in both patients, who could not be diagnosed with either RP or CRD because of the severe retinal degeneration and early onset disease. Longitudinal follow-up of the patients revealed highly progressive retinal degeneration, macular atrophy, and visual field loss. CONCLUSIONS: Recessive C8orf37 mutations have been identified in early to adolescent-onset arRP and arCRD with macular involvement. Our study identified two novel truncating mutations of the C8orf37 gene in siblings with early-onset retinal dystrophy, macular atrophy, cataracts, and high myopia. PMID- 25113447 TI - Growth, photosynthetic acclimation and yield quality in legumes under climate change simulations: an updated survey. AB - Continued emissions of CO2, derived from human activities, increase atmospheric CO2 concentration. The CO2 rise stimulates plant growth and affects yield quality. Effects of elevated CO2 on legume quality depend on interactions with N2 fixing bacteria and mycorrhizal fungi. Growth at elevated CO2 increases photosynthesis under short-term exposures in C3 species. Under long-term exposures, however, plants generally acclimate to elevated CO2 decreasing their photosynthetic capacity. An updated survey of the literature indicates that a key factor, perhaps the most important, that characteristically influences this phenomenon, its occurrence and extent, is the plant source-sink balance. In legumes, the ability of exchanging C for N at nodule level with the N2-fixing symbionts creates an extra C sink that avoids the occurrence of photosynthetic acclimation. Arbuscular mycorrhizal fungi colonizing roots may also result in increased C sink, preventing photosynthetic acclimation. Defoliation (Anthyllis vulneraria, simulated grazing) or shoot cutting (alfalfa, usual management as forage) largely increases root/shoot ratio. During re-growth at elevated CO2, new shoots growth and nodule respiration function as strong C sinks that counteracts photosynthetic acclimation. In the presence of some limiting factor, the legumes response to elevated CO2 is weakened showing photosynthetic acclimation. This survey has identified limiting factors that include an insufficient N supply from bacterial strains, nutrient-poor soils, low P supply, excess temperature affecting photosynthesis and/or nodule activity, a genetically determined low nodulation capacity, an inability of species or varieties to increase growth (and therefore C sink) at elevated CO2 and a plant phenological state or season when plant growth is stopped. PMID- 25113448 TI - Methodological advances: using greenhouses to simulate climate change scenarios. AB - Human activities are increasing atmospheric CO2 concentration and temperature. Related to this global warming, periods of low water availability are also expected to increase. Thus, CO2 concentration, temperature and water availability are three of the main factors related to climate change that potentially may influence crops and ecosystems. In this report, we describe the use of growth chamber - greenhouses (GCG) and temperature gradient greenhouses (TGG) to simulate climate change scenarios and to investigate possible plant responses. In the GCG, CO2 concentration, temperature and water availability are set to act simultaneously, enabling comparison of a current situation with a future one. Other characteristics of the GCG are a relative large space of work, fine control of the relative humidity, plant fertirrigation and the possibility of light supplementation, within the photosynthetic active radiation (PAR) region and/or with ultraviolet-B (UV-B) light. In the TGG, the three above-mentioned factors can act independently or in interaction, enabling more mechanistic studies aimed to elucidate the limiting factor(s) responsible for a given plant response. Examples of experiments, including some aimed to study photosynthetic acclimation, a phenomenon that leads to decreased photosynthetic capacity under long-term exposures to elevated CO2, using GCG and TGG are reported. PMID- 25113450 TI - Inconsistency of mesophyll conductance estimate causes the inconsistency for the estimates of maximum rate of Rubisco carboxylation among the linear, rectangular and non-rectangular hyperbola biochemical models of leaf photosynthesis--a case study of CO2 enrichment and leaf aging effects in soybean. AB - The responses of CO2 assimilation to [CO2] (A/Ci) were investigated at two developmental stages (R5 and R6) and in several soybean cultivars grown under two levels of CO2, the ambient level of 370 MUbar versus the elevated level of 550 MUbar. The A/Ci data were analyzed and compared by either the combined iterations or the separated iterations of the Rubisco-limited photosynthesis (Ac) and/or the RuBP-limited photosynthesis (Aj) using various curve-fitting methods: the linear 2-segment model; the non-rectangular hyperbola model; the rectangular hyperbola model; the constant rate of electron transport (J) method and the variable J method. Inconsistency was found among the various methods for the estimation of the maximum rate of carboxylation (Vcmax), the mitochondrial respiration rate in the light (Rd) and mesophyll conductance (gm). The analysis showed that the inconsistency was due to inconsistent estimates of gm values that decreased with an instantaneous increase in [CO2], and varied with the transition Ci cut-off between Rubisco-limited photosynthesis and RuBP-regeneration-limited photosynthesis, and due to over-parameters for non-linear curve-fitting with gm included. We proposed an alternate solution to A/Ci curve-fitting for estimates of Vcmax, Rd, Jmax and gm with the various A/Ci curve-fitting methods. The study indicated that down-regulation of photosynthetic capacity by elevated [CO2] and leaf aging was due to partially the decrease in the maximum rates of carboxylation and partially the decrease in gm. Mesophyll conductance lowered photosynthetic capacity by 18% on average for the case of soybean plants. PMID- 25113449 TI - Stomatal and mesophyll conductances to CO2 in different plant groups: underrated factors for predicting leaf photosynthesis responses to climate change? AB - The climate change conditions predicted for the end of the current century are expected to have an impact on the performance of plants under natural conditions. The variables which are foreseen to have a larger effect are increased CO2 concentration and temperature. Although it is generally considered CO2 assimilation rate could be increased by the increasing levels of CO2, it has been reported in previous studies that acclimation to high CO2 results in reductions of physiological parameters involved in photosynthesis, like the maximum carboxylation rate (Vc,max), stomatal conductance (gs) and mesophyll conductance to CO2 (gm). On the one hand, most of the previous modeling efforts have neglected the potential role played by the acclimation of gm to high CO2 and temperature. On the other hand, the effect of climate change on plant clades other than angiosperms, like ferns, has received little attention, and there are no studies evaluating the potential impact of increasing CO2 and temperature on these species. In this study we predicted responses of several representative species among angiosperms, gymnosperms and ferns to increasing CO2 and temperature. Our results show that species with lower photosynthetic capacity - such as some ferns and gymnosperms - would be proportionally more favored under these foreseen environmental conditions. The main reason for this difference is the lower diffusion limitation imposed by gs and gm in plants having high capacity for photosynthesis among the angiosperms, which reduces the positive effect of increasing CO2. However, this apparent advantage of low-diffusion species would be canceled if the two conductances - gs and gm - acclimate and are down regulated to high CO2, which is basically unknown, especially for gymnosperms and ferns. Hence, for a better understanding of different plant responses to future climate, studies are urged in which the actual photosynthetic response/acclimation to increased CO2 and temperature of ferns, gymnosperms and other under-evaluated plant groups is assessed. PMID- 25113451 TI - Rubisco catalytic properties optimized for present and future climatic conditions. AB - Because of its catalytic inefficiencies, Rubisco is the most obvious target for improvement to enhance the photosynthetic capacity of plants. Two hypotheses are tested in the present work: (1) existing Rubiscos have optimal kinetic properties to maximize photosynthetic carbon assimilation in existing higher plants; (2) current knowledge allows proposal of changes to kinetic properties to make Rubiscos more suited to changed conditions in chloroplasts that are likely to occur with climate change. The catalytic mechanism of Rubisco results in higher catalytic rates of carboxylation being associated with decreased affinity for CO2, so that selection for different environments involves a trade-off between these two properties. The simulations performed in this study confirm that the optimality of Rubisco kinetics depends on the species and the environmental conditions. In particular, environmental drivers affecting the CO2 availability for carboxylation (Cc) or directly shifting the photosynthetic limitations between Rubisco and RuBP regeneration determine to what extend Rubisco kinetics are optimally suited to maximize CO2 assimilation rate. In general, modeled values for optimal kinetic reflect the predominant environmental conditions currently encountered by the species in the field. Under future climatic conditions, photosynthetic CO2 assimilation will be limited by RuBP-regeneration, especially in the absence of water stress, the largest rise in [CO2] and the lowest increases in temperature. Under these conditions, the model predicts that optimal Rubisco should have high Sc/o and low kcat(c). PMID- 25113452 TI - Will carbon isotope discrimination be useful as a tool for analysing the functional response of barley plants to salinity under the future atmospheric CO2 conditions? AB - The objective of this study was to determine the response of barley's carbon isotope composition and other physiological parameters to the interaction of salt stress and elevated CO2 levels, and the usefulness of carbon isotope discrimination (Delta(13)C) as indicative of the functional performance of barley (Hordeum vulgare L.). Barley plants were grown under ambient (350 MUmol mol(-1)) and elevated (700 MUmol mol(-1)) CO2 conditions and subjected to salt stress (0, 80, 160, and 240 mM NaCl) for 14 days. Elevated CO2 levels increased biomass production, water use efficiency and the photosynthetic rate, although this parameter was partly acclimated to elevated CO2 levels. Salt stress decreased this acclimation response because it enhanced the sink strength of the plant. Elevated CO2 significantly decreased the (13)C isotopic composition (delta(13)C) in all plant organs; however, the ratio of delta(13)C between the root and the leaf was increased, indicating a higher allocation of delta(13)C to the below ground parts. Conversely, salt stress increased plant delta(13)C, showing differences between plant organs. From the strong correlations between Delta(13)C and biomass production, the photosynthetic rate or water use efficiency both at ambient and elevated CO2, we concluded that Delta(13)C is a useful parameter for evaluating leaf and whole plant responses to salinity and can provide an integrated index of processes to understand the mechanisms underlying salt tolerance of barley both under current and future environmental CO2 conditions. PMID- 25113453 TI - Isoprene emission aids recovery of photosynthetic performance in transgenic Nicotiana tabacum following high intensity acute UV-B exposure. AB - Isoprene emission by terrestrial plants is believed to play a role in mitigating the effects of abiotic stress on photosynthesis. Ultraviolet-B light (UV-B) induces damage to the photosynthetic apparatus of plants, but the role of isoprene in UV-B tolerance is poorly understood. To investigate this putative protective role, we exposed non-emitting (NE) control and transgenic isoprene emitting (IE) Nicotiana tabacum (tobacco) plants to high intensity UV-B exposure. Methanol emissions increased with UV-B intensity, indicating oxidative damage. However, isoprene emission was unaffected during exposure to UV-B radiation, but declined in the 48 h following UV-B treatment at the highest UV-B intensities of 9 and 15 Wm(-2). Photosynthesis and the performance of photosystem II (PSII) declined to similar extents in IE and NE plants following UV-B exposure, suggesting that isoprene emission did not ameliorate the immediate impact of UV-B on photosynthesis. However, after the stress, photosynthesis and PSII recovered in IE plants, which maintained isoprene formation, but not in NE plants. Recovery of IE plants was also associated with elevated antioxidant levels and cycling; suggesting that both isoprene formation and antioxidant systems contributed to reinstating the integrity and functionality of cellular membranes and photosynthesis following exposure to excessive levels of UV-B radiation. PMID- 25113454 TI - Overexpression of monoubiquitin improves photosynthesis in transgenic tobacco plants following high temperature stress. AB - The ubiquitin/26S proteasome system (Ub/26S) is implicated in abiotic stress responses in plants. In this paper, transgenic tobacco plants overexpressing Ta Ub2 from wheat were used to study the functions of Ub in the improvement of photosynthesis under high temperature (45 degrees C) stress. We observed higher levels of Ub conjugates in transgenic plants under high temperature stress conditions compared to wild type (WT) as a result of the constitutive overexpression of Ta-Ub2, suggesting increased protein degradation by the 26S proteasome system under high temperature stress. Overexpressing Ub increased the photosynthetic rate (Pn) of transgenic tobacco plants, consistent with the improved ATPase activity in the thylakoid membrane and enhanced efficiency of PSII photochemistry. The higher D1 protein levels following high temperature stress in transgenic plants than WT were also observed. These findings imply that Ub may be involved in tolerance of photosynthesis to high temperature stress in plants. Compared with WT, the transgenic plants showed lower protein carbonylation and malondialdehyde (MDA) levels, less reactive oxygen species (ROS) accumulation, but higher antioxidant enzyme activity under high temperature stress. These findings suggest that the improved antioxidant capacity of transgenic plants may be one of the most important mechanisms underlying Ub regulated high temperature tolerance. PMID- 25113455 TI - Foliar CO2 in a holm oak forest subjected to 15 years of climate change simulation. AB - A long-term experimental drought to simulate future expected climatic conditions for Mediterranean forests, a 15% decrease in soil moisture for the following decades, was conducted in a holm oak forest since 1999. Net photosynthetic rate, stomatal conductance and leaf water potential were measured from 1999 to 2013 in Quercus ilex and Phillyrea latifolia, two co-dominant species of this forest. These measurements were performed in four plots, two of them received the drought treatment and the two other plots were control plots. The three studied variables decreased with increases in VPD and decreases in soil moisture in both species, but the decrease of leaf water potential during summer drought was larger in P. latifolia, whereas Q. ilex reached higher net photosynthetic rates and stomatal conductance values during rainy periods than P. latifolia. The drought treatment decreased ca. 8% the net photosynthetic rates during the overall studied period in both Q. ilex and P. latifolia, whereas there were just non-significant trends toward a decrease in leaf water potential and stomatal conductance induced by drought treatment. Future drier climate may lead to a decrease in the carbon balance of Mediterranean species, and some shrub species well resistant to drought could gain competitive advantage relative to Q. ilex, currently the dominant species of this forest. PMID- 25113456 TI - Opportunities for improving leaf water use efficiency under climate change conditions. AB - WUEi (intrinsic water use efficiency) is a complex (multi)-trait, that depends on several physiological processes, driving plant productivity and its relation with a changing environment. Climatic change predictions estimate increases in temperature and drought in the semi-arid regions, rendering improved water use efficiency is a mandatory objective to maintain the current global food supply. The aims of this review were (i) to identify through a meta-analysis the leaf traits mostly related to intrinsic water use efficiency (WUEi, the ratio between A - net photosynthesis and gs - stomatal conductance), based on a newly compiled dataset covering more than 200 species/varieties and 106 genus of C3 plants (ii) to describe the main potential targets for WUEi improvement via biotechnological manipulations and (iii) to introduce emergent and innovative technologies including UAVs (Unmanned Aerial Vehicles) to scale up levels from leaf to whole plant water status. We confirmed that increases in gm/gs and Vcmax/gs ratios are systematically related with increases in WUEi maintained across species, habitats, and environmental conditions. Other emergent opportunities to improve WUEi are described such as the relationship between photosynthesis and respiration and their link with metabolomics. Finally, we outline our hypothesis that we are observing the advent of a "smart" agriculture, wherein new technologies, such as UAVs equipped with remote sensors will rapidly facilitate an efficient water use regulating the irrigation schedule and determination, under field conditions, of cultivars with improved water use efficiency. We, therefore, conclude that the multi-disciplinary challenge toward WUE has only just begun. PMID- 25113457 TI - Leaf respiration in darkness and in the light under pre-industrial, current and elevated atmospheric CO2 concentrations. AB - Our study sought to understand how past, low atmospheric CO2 concentrations ([CO2]) impact respiration (R) of soybean (Glycine max), when compared to plants grown under current and future [CO2]s. Experiments were conducted using plants grown under 290, 400 and 700 ppm [CO2]. Leaf R was measured in both darkness (RD) and in the light (RL; using the Kok method), with short-term changes in measurement [CO2] and [O2] being used to explore the relationship between light inhibition of leaf R and photorespiration. Root R, photosynthesis (A), leaf [N] and biomass allocation traits were also quantified. In contrast to the inhibitory effect of low growth [CO2] on A, growth [CO2] had no significant effect on leaf RD or root R. Irrespective of growth [CO2], RL was always lower than RD, with light inhibiting leaf R by 17-47%. Importantly, the degree of light inhibition of leaf R was lowest in plants grown under low [CO2], with variations in RL being positively correlated with RD and photorespiration. Irrespective of whether leaf R was measured in the light or dark, a greater proportion of the carbon fixed by leaf photosynthesis was released by leaf R in plants grown under low [CO2] than under current/future [CO2]'s. Collectively, our results highlight the differential responses of A and R to growth of plants under low to elevated atmospheric [CO2]. PMID- 25113458 TI - Limitations to soybean photosynthesis at elevated carbon dioxide in free-air enrichment and open top chamber systems. AB - It has been suggested that the stimulation of soybean photosynthesis by elevated CO2 was less in free-air carbon dioxide enrichment (FACE) systems than in open top chambers (OTC), which might explain smaller yield increases at elevated CO2 in FACE systems. However, this has not been tested using the same cultivars grown in the same location. I tested whether soybean photosynthesis at high light and elevated CO2 (ambient+180 MUmol mol(-1)) was limited by electron transport (J) in FACE systems but by ribulose-bisphosphate carboxylation capacity (VCmax) in OTC. FACE systems with daytime and continuous CO2 enrichment were also compared. The results indicated that in both cultivars examined, midday photosynthesis at high light was always limited by VCmax, both in the FACE and in the OTC systems. Daytime only CO2 enrichment did not affect photosynthetic parameters or limitations, but did result in significantly smaller yields in both cultivars than continuous elevation. Photosynthesis measured at low photosynthetic photon flux density (PPFD) was not higher at elevated than at ambient CO2, because of an acclimation to elevated CO2 which was only evident at low measurement PPFDs. PMID- 25113459 TI - Biochemical acclimation, stomatal limitation and precipitation patterns underlie decreases in photosynthetic stimulation of soybean (Glycine max) at elevated [CO2] and temperatures under fully open air field conditions. AB - The net effect of elevated [CO2] and temperature on photosynthetic acclimation and plant productivity is poorly resolved. We assessed the effects of canopy warming and fully open air [CO2] enrichment on (1) the acclimation of two biochemical parameters that frequently limit photosynthesis (A), the maximum carboxylation capacity of Rubisco (Vc,max) and the maximum potential linear electron flux through photosystem II (Jmax), (2) the associated responses of leaf structural and chemical properties related to A, as well as (3) the stomatal limitation (l) imposed on A, for soybean over two growing seasons in a conventionally managed agricultural field in Illinois, USA. Acclimation to elevated [CO2] was consistent over two growing seasons with respect to Vc,max and Jmax. However, elevated temperature significantly decreased Jmax contributing to lower photosynthetic stimulation by elevated CO2. Large seasonal differences in precipitation altered soil moisture availability modulating the complex effects of elevated temperature and CO2 on biochemical and structural properties related to A. Elevated temperature also reduced the benefit of elevated [CO2] by eliminating decreases in stomatal limitation at elevated [CO2]. These results highlight the critical importance of considering multiple environmental factors (i.e. temperature, moisture, [CO2]) when trying to predict plant productivity in the context of climate change. PMID- 25113460 TI - Impacts of rising tropospheric ozone on photosynthesis and metabolite levels on field grown soybean. AB - The response of leaf photosynthesis and metabolite profiles to ozone (O3) exposure ranging from 37 to 116 ppb was investigated in two soybean cultivars Dwight and IA3010 in the field under fully open-air conditions. Leaf photosynthesis, total non-structural carbohydrates (TNC) and total free amino acids (TAA) decreased linearly with increasing O3 levels in both cultivars with average decrease of 7% for an increase in O3 levels by 10 ppb. Ozone interacted with developmental stages and leaf ages, and caused higher damage at later reproductive stages and in older leaves. Ozone affected yield mainly via reduction of maximum rate of Rubisco carboxylation (Vcmax) and maximum rates of electron transport (Jmax) as well as a shorter growing season due to earlier onset of canopy senescence. For all parameters investigated the critical O3 levels (~50 ppb) for detectable damage fell within O3 levels that occur routinely in soybean fields across the US and elsewhere in the world. Strong correlations were observed in O3-induced changes among yield, photosynthesis, TNC, TAA and many metabolites. The broad range of metabolites that showed O3 dose dependent effect is consistent with multiple interaction loci and thus multiple targets for improving the tolerance of soybean to O3. PMID- 25113461 TI - Acclimation of photosynthetic tolerance to acute heat stress at elevated CO2 and N. AB - Determining interactive effects of pre-heat-stress, CO2 and N on photosynthetic thermotolerance is necessary for predicting plant responses to global change. We grew Hordeum vulgare (barley, C3) and Zea mays (corn, C4) at current or elevated CO2 (370 and 700 ppm) and limiting or optimal soil N (0.5 and 7.5mM). We assessed basal and inducible thermotolerance of net photosynthesis (Pn), photosystem II efficiency [Formula: see text] , photochemical quenching (qp), carboxylation efficiency (CE), and rubisco activase content. Inducible thermotolerance was measured on plants which were pre-heat-stressed (PHS) for 4h before heat stress. We also assayed content of several major heat-shock proteins (HSPs), as HSPs are primary adaptations to heat stress and affected by N. Acclimation of photosynthetic thermotolerance was dependent on species, CO2 and N treatment and the component in the photosynthetic processes. PHS had a positive effect on the production of HSP60 and sHSP in low-N barley and corn. These results indicate that stimulatory effects of elevated CO2 at normal temperatures on photosynthesis may be partly changed by the different interactive effects of CO2, heat stress and N for species with different photosynthetic pathways. Thus, PHS, CO2 and N effects on photosynthetic thermotolerance may contribute to changes in plant productivity, distribution, and diversity. PMID- 25113462 TI - Effects of elevated O3 exposure on seed yield, N concentration and photosynthesis of nine soybean cultivars (Glycine max (L.) Merr.) in Northeast China. AB - Nine soybean cultivars widely cultivated in Northeast China were investigated in present study to assess their O3 sensitivities on the basis of the response of photosynthesis and seed yield to ambient and future ozone (O3) concentrations, and determine whether the effects of O3 vary with the developmental stages (flowering and seed filling stages). Relative to charcoal-filtered air (CF), elevated O3 concentration (E-O3, ambient air+40 ppb) significantly reduced soybean yields by 40%, with a range of 32-46% among cultivars. E-O3 also induced significant decreases in pigment contents, net photosynthetic rate and chlorophyll a fluorescence at both flowering and seed filling stages in most cultivars. Except net photosynthetic rate and stomatal conductance (gs) at seed filling stage, all variables showed no significant interaction between O3 and cultivar, suggesting that all tested cultivars had similar sensitivities to O3. The responses of seed N content to E-O3 differed among cultivars. Ambient O3 concentration (mean of daily concentration of 19 ppb) did not induce any change relative to CF. Significant positive relationship between endogenous gs in CF and yield loss among cultivars was found only at seed filling stage. Positive correlation between effects of E-O3 on leaf N content and effects on light saturated photosynthetic rate (Asat) indicated that gs and leaf N content at seed filling stage contributes to yield loss and decreased photosynthesis by E-O3, respectively. It can be inferred that E-O3 had a larger negative effects on seed filling stage than flowering stage of soybean. PMID- 25113463 TI - Impacts of elevated ozone on growth and photosynthesis of Metasequoia glyptostroboides Hu et Cheng. AB - One-year-old Metasequoia glyptostroboides seedlings were exposed to non-filtered ambient air (NF) and elevated ozone (E-O3, NF+60 ppb) in open-top chambers for two years. E-O3 accelerated leaf senescence, as indicated by significant decreases in photosynthetic pigment contents with the elongation of O3 exposure. E-O3 significantly affected gas exchange and carboxylation, inducing reductions in light-saturated photosynthesis (Asat), the maximum activity of Rubisco (Vc,max) and the maximum electron transport rate (Jmax). Chl a/b, Vc,max/Jmax and stomatal limitation (l) were not affected. Stomatal conductance (gs) was significantly decreased by E-O3 in the first year, but remained unchanged in the second year. It can be inferred that the decrease in Asat by E-O3 was mainly attributed to the changes in non-stomatal factors. After two years' exposure, E O3 caused significant decreases in canopy photosynthesis and leaf mass per area, and a significant increase in the number of branches, but induced slight, not significant decreases in growth and biomass. Therefore, it can be concluded that the carbon accumulation of the species M. glyptostroboides could be negatively affected after long-term exposure to high O3 concentration. PMID- 25113465 TI - Transcriptional networks leading to symbiotic nodule organogenesis. AB - The symbiosis with nitrogen-fixing bacteria leading to root nodules is a relatively recent evolutionary innovation and limited to a distinct order of land plants. It has long been a mystery how plants have invented this complex trait. However, recent advances in molecular genetics of model legumes has elucidated genes involved in the development of root nodules, providing insights into this process. Here we discuss how the de novo assembly of transcriptional networks may account for the predisposition to nodulate. Transcriptional networks and modes of gene regulation from the arbuscular mycorrhizal symbiosis, nitrate responses and aspects of lateral root development have likely all contributed to the emergence and development of root nodules. PMID- 25113466 TI - Au nanoparticle sensitized ZnO nanopencil arrays for photoelectrochemical water splitting. AB - This paper describes the synthesis of Au nanoparticle sensitized ZnO nanopencil arrays on F-doped SnO2 substrates by an aqueous chemical growth and subsequent photoreduction method. The Au-ZnO nanopencil arrays yield a photocurrent of ~ 1.5 mA cm(-2) at 1 V versus Ag/AgCl. The enhanced photocurrent is attributed to the surface plasmon resonance effect of Au nanoparticles and the prolonged lifetime of the photo-generated electron-hole pairs. The improved stability of ZnO is due to the plasmon resonance energy transfer process enabled by the Au nanoparticles, which enhances the electric field intensity in a small, well-defined location of the ZnO semiconductor. PMID- 25113467 TI - Revision of Siobla (Hymenoptera, Tenthredinidae) from Japan. AB - The Japanese species of the sawfly genus Siobla Cameron, 1877, are revised and keyed. The following nine species are recognized: S. apicalis Takeuchi, 1929, S. ferox (Smith, 1874), S. hirasana Takeuchi, 1929, S. jucunda (Mocsary, 1909), S. metallica Takeuchi, 1929, S. sturmii (Klug, 1817), S. japonica, sp. nov., S. pulchra, sp. nov., and S. takeuchii, sp. nov. Siobla pacifica (Smith, 1874) is synonymized with S. sturmii. Lectotypes are designated for Macrophya ferox Smith, 1874, Macrophya pacifica Smith, 1874, Encarsioneura jucunda Mocsary, 1909, and Siobla grandis Matsumura, 1912. Previous records of S. ruficornis (Gimmerthal, 1834) and S. villosa Malaise, 1931, from Japan have been found erroneous. Siobla jucunda is newly recorded from Japan. PMID- 25113468 TI - Revision of the Siobla formosana group (Hymenoptera: Tenthredinidae). AB - 14 species of the Siobla formosana species-group are revised. Three new species: Siobla jiangi Niu & Wei, sp. nov., S. parallela Niu & Wei, sp. nov., S. weiweii Niu & Wei, sp. nov. are described. Siobla rufipes Malaise, 1945 is a new synonym of S. atra Malaise, 1945. The males formerly assigned to S. atra belong to S. semipicta Malaise, 1945. The previously unknown female of Siobla rufopropodea Wei, 1998 is described. Lectotypes are designated for Siobla rufipes Malaise, 1945, Siobla atra Malaise, 1945 and Siobla semipicta Malaise, 1945. The previously described species are illustrated and partly redescribed. A key to species of the group is given. Distribution records of each species of the group except S. takeuchii are given. PMID- 25113470 TI - A checklist of the Kateretidae and Nitidulidae of Iran (Coleoptera: Cucujoidea). AB - The current knowledge of the geographic distribution of short-winged flower beetles and sap beetles (Kateretidae and Nitidulidae, respectively) from Iran is summarized. In total, 84 species of Nitidulidae (in 22 genera and 5 subfamilies: Epuraeinae, Carpophilinae, Cryptarchinae, Nitidulinae, Meligethinae) and 6 species of Kateretidae (in 4 genera: Brachyleptus Motschulsky, Brachypterolus Grouvelle, Brachypterus Kugelann, Kateretes Herbst) are listed. Brachyleptus discolor Reitter, Brachypterus glaber (Newman) (both Kateretidae), Epuraea distincta (Grimmer), Soronia oblonga (Brisout), Lamiogethes bidens (Brisout), Lamiogethes medvedevi (Kirejtshuk), Sagittogethes devillei (Grouvelle) and Xerogethes rotundicollis (Brisout) (Nitidulidae) are new records for Iran. PMID- 25113469 TI - Review of the Eulamprotes wilkella species-group based on morphology and DNA barcodes, with descriptions of new taxa (Lepidoptera, Gelechiidae). AB - The Eulamprotes wilkella species-group is revised based on morphological characters and on DNA barcodes of the mtCOI (Cytochrome c Oxidase 1) gene. Adult morphology combined with sequence information for 9 species supports the existence of 12 species, 7 of which are described as new to science: E. mirusella Huemer & Karsholt sp. nov. (France), E. baldizzonei Karsholt & Huemer sp. nov. (Italy, Slovenia, Croatia), E. atrifrontella Karsholt & Huemer sp. nov. (Turkey), E. wieseri Huemer & Karsholt sp. nov. (Kyrgizia), E. altaicella Huemer & Karsholt sp. nov. (Russia: Altai, Buryatia, Tuva Republic), E. kailai Karsholt & Huemer sp. nov. (Kazakhstan, Kyrgizia, Russia: Buryatia, Tuva Republic) and E. gemerensis Elsner sp. nov. (Slovakia). E. buvati Leraut, 1991 syn. nov. is synonymized with E. ochricapilla (Rebel, 1903). PMID- 25113471 TI - A cryptic new species of Miniopterus from south-eastern Africa based on molecular and morphological characters. AB - Resolving species limits within the genus Miniopterus has traditionally been complicated by the presence of cryptic species with overlapping morphological features. We use molecular techniques, cranio-dental characters and tragus shape to describe a new species of Miniopterus from Mozambique, M. mossambicus. Miniopterus mossambicus shows > 12% divergence in cytochrome-b sequence from its nearest congeners (the Malagasy M. gleni and M. griveaudi) and > 15% divergence from the morphologically similar M. natalensis, M. fraterculus and M. minor (all of which occur in southern and eastern Africa). There is considerable overlap in cranio-dental characters of the southern African species, particularly M. natalensis and M. mossambicus. However, tragus shape and multivariate comparisons of skull measurements can be used to separate these species. Based on morphological comparisons of museum specimens, this species may also be present in neighbouring Malawi and Zimbabwe, suggesting that it is probably distributed widely in south-central Africa. PMID- 25113472 TI - Review of the genus Cidariplura Butler, 1879 (Lepidoptera, Erebidae, Herminiinae) in Taiwan with descriptions of four new species. AB - The genus Cidariplura Butler, 1879 from Taiwan is reviewed. A total of seven species are confirmed to occur in this old landbridge island, and four new species are described: C. shanmeii Wu & Owada sp. nov., C. maraho Wu & Owada sp. nov., C. atayal Wu & Owada sp. nov. and C. ilana Wu & Owada sp. nov. The Taiwanese C. bilineata (Wileman & South, 1919) is superficially similar to the Indian and Nepalese C. brevivittalis (Moore, 1867) but their genitalia show distinct differences. Elyra albifascia Hampson 1929 is regarded as a junior synonym of C. brevivittalis (syn. nov.). All diagnostic characteristics of Cidariplura from Taiwan and its adjacent areas are illustrated. PMID- 25113473 TI - New records of Recent Brachiopoda from the Red Sea with a description of a new species . AB - A revised checklist of 14 Recent brachiopod species from Egypt and the Sudan in the Red Sea has been compiled. New records of Minutella minuta (Cooper), Thecidellina blochmanni Dall and Argyrotheca somaliensis Cooper are described and a new species Argyrotheca cooperi is erected for specimens with few but very strong costae. The new records support earlier suggestions that the affinities of the Red Sea brachiopod fauna are with those of the Mediterranean and Indo-Pacific areas. PMID- 25113474 TI - A new species of fiddler crab from the Ogasawara (Bonin) Islands, Japan, separated from the widely-distributed sister species Uca (Paraleptuca) crassipes (White, 1847) (Crustacea: Decapoda: Brachyura: Ocypodidae). AB - A new species of fiddler crab (Brachyura: Ocypodidae), Uca boninensis sp. nov., is described from the Ogasawara (Bonin) Islands, Japan. The new species has previously been identified with the widely distributed U. crassipes (White, 1847), from which it differs by having a slightly differently shaped carapace, and relatively stouter male first gonopods (G1). The recognition of the new species is also supported by differences in the mitochondrial cytochrome oxidase I (COI) and control region (CR) genes. U. boninensis sp. nov., appears to be endemic to the Ogasawara Islands, and as the only known population is small, urgent conservation measures are needed for its protection. Our study brings the total number of the Japanese fiddler crab species to 12. PMID- 25113475 TI - A new form of Elongatoolithidae, Undulatoolithus pengi oogen. et oosp. nov. from Pingxiang, Jiangxi, China. AB - A new oogenus and oospecies of the Elongatoolithidae, Undulatoolithus pengi oogen. et oosp. nov., is described on the basis of specimens from the Upper Cretaceous Zhoutian Formation of the Pingxiang Basin, Jiangxi Province, China. The eggs are slightly asymmetrical, paired, and lay radially-oriented in a circular configuration within the clutch, and most suggestive of Macroolithus of the Elongatoolithidae by medium-sized eggs with average polar axis and equatorial diameter of 19.36 and 8.35 cm, and the ornamentation pattern of nodes and ridges on the outer surface. The new oogenus differs from Macroolithus in its prominent ridges 0.67 mm in height, about half of the entire eggshell thickness, gradational boundary between the cone layer and the overlying columnar layer, cone layer-to-columnar layer thickness ratio of 1/8 or 1/4. This discovery adds new data on the morphology and diversification of Late Cretaceous elongatoolithid ootaxa. PMID- 25113476 TI - A new dasyurid marsupial from Kroombit Tops, south-east Queensland, Australia: the Silver-headed Antechinus, Antechinus argentus sp. nov. (Marsupialia: Dasyuridae). AB - Antechinus argentus sp. nov. is currently only known from the plateau at the eastern escarpment of Kroombit Tops National Park, about 400km NNW of Brisbane and 60km SSW of Gladstone, south-east Queensland, Australia. Antechinus flavipes (Waterhouse) is also known from Kroombit Tops NP, 4.5km W of the nearest known population of A. argentus; A. mysticus Baker, Mutton and Van Dyck has yet to be found within Kroombit Tops, but is known from museum specimens taken at Bulburin NP, just 40km ESE, as well as extant populations about 400km to both the south east and north-west of Kroombit NP. A. argentus can be easily distinguished in the field, having an overall silvery/grey appearance with much paler silver feet and drabber deep greyish-olive rump than A. flavipes, which has distinctive yellow-orange toned feet, rump and tail-base; A. argentus fur is also less coarse than that of A. flavipes. A. argentus has a striking silver-grey head, neck and shoulders, with pale, slightly broken eye-rings, which distinguish it from A. mysticus which has a more subtle greyish-brown head, pale buff dabs of eyeliner and more colourful brownish-yellow rump. Features of the dentary can also be used for identification: A. argentus differs from A. flavipes in having smaller molar teeth, as well as a narrower and smaller skull and from A. mysticus in having on average a narrower snout, smaller skull and dentary lengths and smaller posterior palatal vacuities in the skull. A. argentus is strongly divergent genetically (at mtDNA) from both A. flavipes (9.0-11.2%) and A. mysticus (7.2-7.5%), and forms a very strongly supported clade to the exclusion of all other antechinus species, in both mtDNA and combined (mtDNA and nDNA) phylogenies inferred here. We are yet to make detailed surveys in search of A. argentus from forested areas to the immediate east and north of Kroombit Tops. However, A. mysticus has only been found at these sites in low densities in decades past and not at all in several recent trapping expeditions conducted by the authors. With similar habitat types in close geographic proximity, it is plausible that A. argentus may be found outside Kroombit. Nevertheless, it is striking that from a range of surveys conducted at Kroombit Tops in the last 15 years and intensive surveys by the authors in the last 3 years, totalling more than 5 080 trap nights, just 13 A. argentus have been captured from two sites less than 6 km apart. If this is even close to the true geographic extent of the species, it would possess one of the smallest distributions of an Australian mammal species. With several threats identified, we tentatively recommend that A. argentus be listed as Endangered, pending an exhaustive trapping survey of Kroombit and surrounds. PMID- 25113477 TI - Revision of the genus Ortopla Walker, [1859] with description of two new species from Southeast Asia (Lepidoptera, Noctuidae, Pantheinae). Revision of Pantheinae, contribution X. AB - The pantheine genus Ortopla Walker, [1859] 1858 is revised. Two new species, Ortopla witti sp. n. from the Philippines and O. longiuncus sp. n. from Nepal, Vietnam, Thailand, Myanmar and South China are described. The name O. commutanda Warren, 1891 (syn. n.) is synonymised with O. iarbasalis Walker, [1859] 1858. The distribution of species in East Asia is clarified. A checklist of the genus Ortopla is presented. Imagines, male and female genitalia of all species are illustrated. PMID- 25113478 TI - Review and revision of Australian Germalus Stal, with new genera and further new species of Australian Geocorinae (Hemiptera: Heteroptera: Geocoridae). AB - During a review of Australian Germalus Stal, types of all species recorded from Australia, as well as of the type species G. kinbergi Stal, originally described from Mauritius Island, were examined and illustrated to redefine and redescribe the genus as well as all the included species. As a result of this, the following synonymies have become necessary: G. humeralis Distant as junior synonym of G. victoriae Bergroth; G. roseobistriatus Kirkaldy as junior synonym of G. lineolosus Distant. Lectotype females have been designated for Germalus victoriae Bergroth, and Germalus lineolosus Distant. The following new taxa have been discovered in the material available for this study: Germalus australis Malipatil sp. nov., Germalus fuscovittatus Malipatil sp. nov., Germalus littoralis Malipatil sp. nov., Capitostylus kurandae Malipatil gen. et sp. nov., Unicageocoris griseus Malipatil gen. et sp. nov., and Ausogeocoris westraliensis Malipatil gen. et sp. nov. Keys to the six genera of Geocorinae, and to the six species of Germalus, now recognised in Australia, are provided. PMID- 25113479 TI - Revised world catalogue of Eucopina, Eucosma, Pelochrista, and Phaneta (Lepidoptera: Tortricidae: Eucosmini). AB - A revised world catalogue of Eucopina, Eucosma, Pelochrista, and Phaneta is provided. Assignment to genus is based on generic redescriptions by Gilligan et al. (2013). A total of 709 names (including subspecies and synonyms) are listed, including 251 new combinations and 52 revised combinations. PMID- 25113480 TI - Four new species of Noeetomima Enderlein (Diptera: Lauxaniidae), with a key to world species. AB - The following four species are described as new to science: Noeetomima chinensis sp. nov. (China), N. jinpingensis sp. nov. (China, Nepal), N. tengchongica sp. nov. (China) and N. yunnanica sp. nov. (China). The species Noeetomima aberrans Shatalkin and N. nepalensis Stuckenberg are newly recorded for Japan and India, respectively, and the male genitalia for N. thaiensis Sasakawa are described and illustrated for the first time. A key to separate world species is presented, as is a detailed checklist of all species. PMID- 25113481 TI - Phytoseiid mites (Acari) associated with yerba mate in southern Brazil, with description of a new species. AB - Yerba mate is a plant of great socioeconomic importance in southern South America. Little has been published about the phytoseiid mite fauna of yerba mate. This paper presents information about the morphology and distribution of phytoseiid mites collected in yerba mate in the Ilopolis and Putinga counties of Brazil between 2002 and 2004. Four areas with of different forms of cultivation in every county were sampled. A list of the species recorded from that state, and a key for their identification are provided. Sixteen phytoseiid mites species were identified, belonging to 11 genera in the subfamilies Amblyseiinae (13 species) and Typhlodrominae (three species). The most abundant genus was Amblyseius with three species. Phytoscutus sexpilis Muma, 1961 and Typhloseiopsis dorsoreticulatus Lofego, Demite & Feres, 2011 are reported for the first time from Rio Grande do Sul state. This study also includes the description of a new species, Typhlodromips pallinii n. sp. PMID- 25113482 TI - Timoides agassizii Bigelow, 1904, little-known hydromedusa (Cnidaria), appears briefly in large numbers off Oman, March 2011, with additional notes about species of the genus Timoides. AB - A bloom of the hydromedusan jellyfish, Timoides agassizii, occurred in February 2011 off the coast of Sohar, Al Batinah, Sultanate of Oman, in the Gulf of Oman. This species was first observed in 1902 in great numbers off Haddummati Atoll in the Maldive Islands in the Indian Ocean and has rarely been seen since. The species appeared briefly in large numbers off Oman in 2011 and subsequent observation of our 2009 samples of zooplankton from Sohar revealed that it was also present in low numbers (two collected) in one sample in 2009; these are the first records in the Indian Ocean north of the Maldives. Medusae collected off Oman were almost identical to those recorded previously from the Maldive Islands, Papua New Guinea, the Marshall Islands, Guam, the South China Sea, and Okinawa. T. agassizii is a species that likely lives for several months. It was present in our plankton samples together with large numbers of the oceanic siphonophore Physalia physalis only during a single month's samples, suggesting that the temporary bloom off Oman was likely due to the arrival of mature, open ocean medusae into nearshore waters. We see no evidence that T. agassizii has established a new population along Oman, since if so, it would likely have been present in more than one sample period. We are unable to deduce further details of the life cycle of this species from blooms of many mature individuals nearshore, about a century apart. Examination of a single damaged T. agassizii medusa from Guam, calls into question the existence of its congener, T. latistyla, known only from a single specimen. PMID- 25113484 TI - First record of the bee genus Homalictus Cockerell for China with description of a new species (Hymenoptera: Halictidae: Halictini). AB - This paper reports the first record of the genus Homalictus from China. We describe and illustrate H. (H.) nabanensis sp. n. collected from the Naban River Watershed National Nature Reserve, Xishuangbanna, Yunnan, China. The type specimens are deposited in Institute of Zoology, Chinese Academy of Sciences, Beijing, China. PMID- 25113483 TI - New bioacoustic and distributional data on Bokermannohyla sapiranga Brandao et al., 2012 (Anura: Hylidae): revisiting its diagnosis in comparison with B. pseudopseudis (Miranda-Ribeiro, 1937). AB - In this paper, we provide new bioacoustic and distributional data on Bokermannohyla sapiranga, as well as additional comparative bioacoustic data on topotypes of B. pseudopseudis, and re-evaluate the differential diagnosis of the former species with respect to the latter. Head shapes (dorsal and lateral views) presented such variation that should not be used to differentially diagnose them as originally proposed. On the other hand, the presence of a dermal ridge along outer tarsi, and color patterns of the eyes and dorsal surface of hand/toe disks still represent diagnostic characters between both species. We also found differences in temporal (call duration; notes per call), spectral (dominant frequency; harmonics), and structural (pulsed/non-pulsed note structure) traits of their calls. Distribution of B. sapiranga is extended eastward (Paracatu), which corresponds to the first record for the State of Minas Gerais, whereas B. pseudopseudis distribution seems to be restricted to rocky montane field environments of northern Goias State. PMID- 25113485 TI - An integrative appraisal of the diagnosis and distribution of Allobates sumtuosus (Morales, 2002) (Anura, Aromobatidae). AB - We describe the advertisement calls and color in life of Allobates sumtuosus (Morales 2002) based on specimens recorded and collected at its type locality in Reserva Biologica do Rio Trombetas, Brazilian Amazonia. We also improve the species diagnosis by adding information on states of characters frequently used in current Allobates taxonomy. Finally, we analyze genetic distances and the evolutionary relationships between typical A. sumtuosus and other Allobates species distributed in Brazil and along the Guiana Shield region using a fragment of the 16S rDNA mitochondrial gene. Based on this integrative analysis, we propose the synonym of Allobates spumaponens Kok & Ernst 2007 with A. sumtuosus and provide an updated geographic distribution of the species. PMID- 25113486 TI - Revision of the Old World genera Panthea Hubner, [1820] 1816 and Pantheana Hreblay, 1998 with description two new species from China (Lepidoptera, Noctuidae: Pantheinae). Revision of Pantheinae, contribution IX. AB - The Old World species of the genus Panthea Hubner [1820] 1816 are revised. The article contains the description of two new species Panthea fuscogrisea sp. n. and Panthea florianii sp. n. from continental China and re-description of two species P. roberti Joannis 1928 and P. grisea Wileman, 1919 with illustration of male and female genitalia. Diphthera hoenei Draudt, 1950 (syn. n.) is synonymised with P. roberti Joannis 1928. The species Panthea ronnyi Thony, 1996 is excluded from the genus Panthea. Lectotypes for Diphthera hoenei and Panthea roberti are designated. The genus includes five species in the Old World, distributed mainly in Sino-Himalayan subregion of the Palaearctic. A checklist of species of the genus Panthea is presented. The little-known genus Pantheana Hreblay, 1998 with the sole species Pantheana yangzisherpana Hreblay, 1998 is reviewed. The imagines, male and female genitalia of all Old World species of Panthea and Pantheana are illustrated. PMID- 25113488 TI - A new species of water mite (Acari, Hydrachnidia) from Assam, India, found in the gut contents of the fish Botia dario (Botiidae). AB - Water mites (Hydrachnidia) occur sporadically in the gut of freshwater fishes. In this study, nine water mite items were found in the gut contents of the fish Botia dario (Hamilton, 1822) (Botiidae) collected in a floodplain wetland (beel) in the river island Majuli, Assam, India. Torrenticola episce is described as new to science; Torrenticola haliki Pesic & Smit 2010, Monatractides oxystomus (K. Viets, 1935) and Hygrobates cf. sinensis Uchida & Imamura, 1951, are reported for the first time from India. PMID- 25113487 TI - The "Rhampholeon uluguruensis complex" (Squamata: Chamaeleonidae) and the taxonomic status of the pygmy chameleons in Tanzania. AB - The specific status of several pygmy chameleons endemic to mountain massifs in the Eastern Arc Mountains, Tanzania has long been controversial due to their lack of distinctive morphological characters. In this work we extend our previous sampling of Rieppeleon and Rhampholeon species, especially from the Rhampoleon moyeri/Rhampholeon uluguruensis complex, and add data from a new mitochondrial marker to address this problem. Our results show that there is geographical structure between populations of pygmy chameleons from different mountains. This structure is especially well defined for Rhampholeon (Rhinodigitum). Phylogenetic analyses confirm that both Rh. uluguruensis Tilbury and Emmrich, 1995 and Rh. moyeri Menegon, Salvidio and Tilbury, 2002 are distinct lineages, the former from the Uluguru Mountains and the latter from the Udzungwa Mountains. However, the paratype material used to erect Rh. moyeri belongs to a separate lineage from the holotype. Similarly, a number of additional lineages within the Rh. moyeri/Rh. uluguruensis complex recovered in the analysis may deserve specific status. At present, there is a lack of morphological characters that can be used to distinguish these lineages, suggesting that there are multiple cryptic taxa in this complex. PMID- 25113489 TI - A new species of karst-adapted Cnemaspis Strauch, 1887 (Squamata: Gekkonidae) from a threatened karst region in Pahang, Peninsular Malaysia. AB - A new species of karst-adapted gekkonid lizard of the genus Cnemaspis Strauch is described from Gua Gunting and Gua Goyang in a karst region of Merapoh, Pahang, Peninsular Malaysia whose unique limestone formations are in immediate danger of being quarried. The new species differs from all other species of Cnemaspis based on its unique suite of morphological and color pattern characters. Its discovery underscores the unique biodiversity endemic to karst regions and adds to a growing list of karst-adapted reptiles from Peninsular Malaysia. We posit that new karst-adapted species endemic to limestone forests will continue to be discovered and these regions will harbor a significant percentage of Peninsular Malaysia's biodiversity and thusly should be conserved rather than quarried. PMID- 25113490 TI - New and little known species of Nemouridae (Plecoptera) from Inner Mongolia of China. AB - Four species of the family Nemouridae, Amphinemura helanshana sp. n., A. didyma Zhu & Yang, Nemoura geei Wu, and Nemoura cf. securigera Klapalek were collected during a two years survey of the Helan Mountains of Inner Mongolia, China. Nemoura cf. securigera has not been collected for more than one hundred years. PMID- 25113491 TI - Two new species of the leafhopper genus Anidiocerus (Hemiptera: Cicadellidae: Idiocerinae) from China. AB - Two new species of Anidiocerus from China, A. brevispinus Xue & Zhang sp. nov. and A. longimus Xue & Zhang sp. nov. are described and illustrated, and A. variabilis Maldonado-Capriles, 1976 is placed as a senior synonym of A. flavidus Cai & Shen, 1998, syn. nov. A redescription of the genus is provided together with a checklist and key for the separation of males. PMID- 25113492 TI - Heleodromia Haliday newly found in Tibet with description of one new species (Diptera: Empidoidea: Trichopezinae). AB - Heleodromia Haliday is recorded from Tibet for the first time with the following three species belonging to the subgenus Heleodromia: Heleodromia (Heleodromia) ausobskyi Wagner, Heleodromia (Heleodromia) basiflava sp. nov. and H. (H.) immaculata Haliday. This finding extends the distribution of Heleodromia in China from Northwest China to Southwest China. A key to the known species of Heleodromia from the Himalayas is presented. PMID- 25113493 TI - The male and larvae of Nigritothrips longistylosus (Thysanoptera, Thripidae) with observations on its biology. AB - The male and larvae of Nigritothrips longistylosus (Priesner) are described for the first time. The life cycle, seasonal abundance, natural enemies and host plant relationships are described. This is the first record of this species from the Iberian Peninsula. PMID- 25113494 TI - Thailand Agromyzidae (Diptera)-2. AB - The 29 species of the subfamily Agromyzinae in Thailand are revised, among these 13 species are described as new to science: Melanagromyza ancyla sp. nov., M. catalexis sp. nov., M. cirrappendicula sp. nov., M. lunulata sp. nov., M. macilenta sp. nov., M. multistriata sp. nov., M. pandiculata sp. nov., M. sexseriata sp. nov., M. spinuliloba sp. nov., M. turgida sp. nov., Ophiomyia flagellata sp. nov., O. quadrifida sp. nov., O. striata sp. nov.; and nine species (three species of Agromyza, two of Melanagromyza and four of Ophiomyia) are recorded as new to Thailand. One new synonym is established: Melanagromyza cordiophoeta Spencer, 1961, as a junior synonym of M. dolichostigma Meijere, 1922. Keys to the Thailand species of the genera Agromyza, Melanagromyza and Ophiomyia are given. PMID- 25113495 TI - Calappid and leucosiid crabs (Crustacea: Decapoda: Brachyura) from Kerala, India, with the description of a new species of Mursia Desmarest, 1823, from the Arabian Sea and redescription of M. bicristimana Alcock & Anderson, 1894. AB - Eleven species of calappid and leucosiid crabs were identified from by-catch landed by trawlers at four fishing ports in Kerala, India that were surveyed in 2007 and supplemented by material obtained in January 2013. Four species are reported for the first time from India, six are new records for Kerala. The status of Mursia bicristimana Alcock & Anderson, 1894, is clarified and the species redescribed. A new species of Mursia is described from the Gulf of Aden, Arabian Sea. PMID- 25113496 TI - Taxonomic study of Bathygadidae fishes (Gadiformes) from Atlantic Spanish waters combining morphological and molecular approaches. AB - From 2009 to 2011 eleven specimens belonging to four bathygadid species of the family Bathygadidae were captured in two different locations in the northern waters of Spain. The morphometric measurements and meristic characters of these specimens are given. The specimens were identified as belonging to the genera Gadomus Regan, 1903, and Bathygadus Gunther, 1878, including the following species: Gadomus dispar (Vaillant, 1888), Gadomus longifilis (Goode & Bean, 1885), Gadomus arcuatus (Goode & Bean, 1886) and Bathygadus melanobranchus Vaillant, 1888. As a result, a new northern limit of distribution of G. arcuatus from the northeastern Atlantic is reported. The first molecular identification and genetic interrelationships of Bathygadidae species, based on the mitochondrial COI nucleotide sequences -DNA barcodes- is reported. Sequences corresponding to specimens from the same species were identical and the overall mean genetic diversity (uncorrected p-distance) was 0.096 +/- 0.008. Based on a morphological and meristic examination of the specimens, as well as on the available literature, an updated key of the members of the family Bathygadidae from the north-eastern Atlantic Ocean is provided. PMID- 25113497 TI - A new species of Murina (Mammalia: Chiroptera: Vespertilionidae) from peninsular Thailand. AB - A new species of Murina belonging to 'suilla-group' is described based on two specimens collected with harp traps in lowland evergreen forest in the southernmost part of peninsular Thailand. Morphology and molecular (mitochondrial COI) data suggest that the new species is most closely related to M. eleryi, which is currently known from Indochina. The new species, however, can be distinguished by the size and shape of the upper canine, the shape of the upper and lower premolars, and the colour of the ventral pelage. Additional data on bacular morphology, echolocation, ecology, and distribution are included. PMID- 25113498 TI - The identity of the genus Scatocoenosia Schnabl, 1915 (Diptera: Muscidae). AB - A re-description is given of the problematic genus and species Scatocoenosia cordyluraeformis Schnabl, 1915. Illustrations of the male and female terminalia, and images of the female holotype and the male of this species, are given. The syno-nymy of Scatocoenosia Schnabl, 1915 with Spilogona Schnabl, 1911 is confirmed, and notes are given on the relationships of S. cordyluraeformis with other Spilogona species. PMID- 25113499 TI - Description of the male genitalia of Belminus rugulosus Stal and Belminus corredori Galvao & Angulo, and comments on the holotype of Parabelminus yurupucu Lent & Wygodzinsky (Hemiptera: Heteroptera: Reduviidae: Triatominae: Bolboderini). AB - The male genitalia of Belminus rugulosus Stal and Belminus corredori Galvao & Angulo are described and illustrated for the first time. Comments on the holotype of Parabelminus yurupucu Lent & Wygodzinsky are presented (Hemiptera: Heteroptera: Reduviidae: Triatominae: Bolboderini). A discussion on previous data in the literature on male genitalia of species of Belminus Stal is provided. PMID- 25113500 TI - The genus Orestias (Teleostei: Cyprinodontidae): nomenclatural errors in the assignation of species names. PMID- 25113504 TI - The biosafety of lanthanide upconversion nanomaterials. AB - Lanthanide upconversion nanophosphors (UCNPs) show unique upconversion luminescence where lower-energy photons (such as near-infrared (NIR) excitation) are converted into higher-energy photons covering the NIR to the UV region, and are considered to have a bright future in clinical translation. As UCNPs are used in a significant number of potential bio-applications, their biosafety is important and has attracted significant attention. In this critical review, recent reports regarding the cellular internalization, biodistribution, excretion, cytotoxicity and in vivo toxic effects of UCNPs are reviewed. In particular, the studies which evaluated the association between the chemical and physical properties of UCNPs and their biodistribution, excretion, and toxic effects are presented in detail. Finally, we also discuss the challenges of ensuring the biosafety of UCNPs in vivo. PMID- 25113502 TI - Fair and unfair punishers coexist in the Ultimatum Game. AB - In the Ultimatum Game, a proposer suggests how to split a sum of money with a responder. If the responder rejects the proposal, both players get nothing. Rejection of unfair offers is regarded as a form of punishment implemented by fair-minded individuals, who are willing to impose the cooperation norm at a personal cost. However, recent research using other experimental frameworks has observed non-negligible levels of antisocial punishment by competitive, spiteful individuals, which can eventually undermine cooperation. Using two large-scale experiments, this note explores the nature of Ultimatum Game punishers by analyzing their behavior in a Dictator Game. In both studies, the coexistence of two entirely different sub-populations is confirmed: prosocial punishers on the one hand, who behave fairly as dictators, and spiteful (antisocial) punishers on the other, who are totally unfair. The finding has important implications regarding the evolution of cooperation and the behavioral underpinnings of stable social systems. PMID- 25113503 TI - [Abdominal pain and ascites formation in a 72-year-old woman]. AB - A 72-year-old woman presented with abdominal pain after micturition. Abdominal ultrasound screening revealed ascites associated with acute renal failure. Paracentesis of the peritoneal fluid was performed. Biochemical analysis indicated a peritoneal transsudate and increased creatinine. Cystoscopy detected a rupture of the urinary bladder. Catheterization and antibiotic therapy resulted in an improvement of pain and closure of the hole in the urinary bladder wall. Several different disorders can induce a rupture of the urinary bladder. In this case, severe chronic constipation was the most probable causative disease. PMID- 25113505 TI - Solitary fibrous tumors of the pleura with Doege-Potter syndrome: a case report and three-decade review of the literature. AB - BACKGROUND: No case of solitary fibrous tumor of the pleura with Doege-Potter syndrome has been reported in China. This study was to report a rare repeatedly recurrent case of solitary fibrous tumor of the pleura with Doege-Potter syndrome diagnosed in China and a three-decade literature review of solitary fibrous tumor of the pleura with Doege-Potter syndrome worldwide. CASE PRESENTATION: A rare case of solitary fibrous tumor of the pleura with Doege-Potter syndrome was diagnosed in 2005 with follow-up to 2011. All medical records were collected and literature of solitary fibrous tumor of the pleura with Doege-Potter syndrome from 1979 to 2011 was obtained through Medline. This typical case, diagnosed and confirmed by histopathologic results, was a 72-year-old Chinese woman who had a complaint of night sweat for a month. A localized mass 12 cm * 11 cm * 8 cm in size was found associated with pleural effusion in her left low chest cavity, and blood tests showed severe hypoglycemia. Removal of the mass solved the hypoglycemia. The case was repeatedly recurrent in April, 2010 and March, 2011 and had no signs of recurrence up to the end of 2011 after surgery. A review of 45 cases of solitary fibrous tumor of the pleura with Doege-Potter syndrome compared and summarized clinical characteristics, treatments, and outcomes by benign and malignant tumor nature. CONCLUSIONS: Incidence of solitary fibrous tumor of the pleura with Doege-Potter syndrome is similar between genders. There are no significant differences in clinical characteristics between benign and malignant cases. Surgery is the first effective treatment for solitary fibrous tumor of the pleura with Doege-Potter syndrome and the completeness of the initial resection is the key to preventing recurrence. Routine follow-up examinations are recommended for early detection of recurrence. PMID- 25113506 TI - Urokinase-type plasminogen activator receptor regulates apoptotic sensitivity of colon cancer HCT116 cell line to TRAIL via JNK-p53 pathway. AB - The urokinase-type plasminogen activator receptor (uPAR) serves not only as an anchor for urokinase-type plasminogen activator but also participates in intracellular signal transduction events. In this study, we investigated whether uPAR could modulate TRAIL-induced apoptosis in human colon cancer cells HCT116. Using an antisense strategy, we established a stable HCT116 cell line with down regulated uPAR. The sensitivity to TRAIL-induced apoptosis was evaluated by FACS analysis. Our results show that the inhibition of uPAR could sensitize HCT116 to TRAIL-induced apoptosis. uPAR inhibition changed the expression of mitochondrial apoptotic pathway proteins, including Bcl-2, Bax, Bid and p53, in a pro-apoptotic manner. We also found that the inhibition of uPAR down-regulated the phosphorylation of FAK, ERK and JNK. The inhibition of p53 by RNA interference rescued cells from enhanced apoptosis, thus indicating that p53 is critical for enhancing TRAIL-induced apoptosis. Furthermore, JNK, but not ERK, inhibition involved in the up-regulation of p53. JNK negatively regulated p53 protein level. Overall, our results show that uPAR inhibition can sensitize colon cancer cells HCT116 to TRAIL-induced apoptosis via active p53 and mitochondrial apoptotic pathways that JNK inhibition is involved. PMID- 25113507 TI - XI-011 enhances cisplatin-induced apoptosis by functional restoration of p53 in head and neck cancer. AB - Head and neck cancer (HNC), one of the most common cancers worldwide, frequently involves mutation of the TP53 gene and dysregulation of the p53 pathway. Overexpression of MDM2 or MDM4 inactivates the tumor-suppressive function of p53. Restoration of p53 function that counteracts these p53 repressors can lead to in vivo tumor regression. Therefore, the present study assessed the ability of the small molecule p53 activator XI-011 (NSC146109) to induce apoptosis in HNC by restoring p53 function. We tested the effects of XI-011 treatment in HNC cell lines, either individually or in combination with cisplatin and assessed growth suppression, cell cycle arrest, and apoptosis. The drug effects on in vivo growth of HNC cells were examined in mice xenograft model. XI-011 exerted the highest growth suppression in tumor cells that overexpress MDM4, in which p53 is degraded. XI-011 treatment downregulated MDM4 mRNA and protein levels, and upregulated expression of proapoptotic genes and promoted apoptosis, in a dose dependent manner. The apoptotic response was blocked by inhibition of p53 or expression of MDM4, demonstrating that the effects of XI-011 depend on p53 and MDM4. In combination treatments, XI-011 acted synergistically with cisplatin to inhibit growth of HNC cells in vitro and in vivo. MDM4 inhibition and functional restoration of p53 by XI-011 effectively enhanced cisplatin-induced cytotoxicity in HNC cells, an activity that suggests a promising strategy for treating HNC. PMID- 25113508 TI - Dexamethasone's effect in the retrocochlear auditory centers of a noise-induced hearing loss mouse model. AB - OBJECTIVE: Examine prophylactic effects of dexamethasone (Dex) in retrocochlear auditory centers in a noise-induced hearing loss (NIHL) mouse model. STUDY DESIGN: Prospective animal study. SETTING: Academic research center. SUBJECTS AND METHODS: Thirty-two mice were divided into control, untreated, saline (2 and 10 uL), and Dex (2 and 10 uL) groups. Dex was applied intratympanically (IT) prior to 110 to 120 dB noise over 6 hours. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were performed at 1 day, 1 week, 1 month, and 2 months. Retrocochlear neuronal cells were labeled with FluoroGold and counted. Hair cells of the organ of Corti were labeled with fluorescein isothiocyanate-conjugated phalloidin and counted. RESULTS: Auditory brainstem response thresholds of untreated NIHL, 2 and 10 uL IT saline, and 2 and 10 uL IT Dex were 21.7 +/- 2.9 dB, 20 +/- 0 dB, 20 +/- 5 dB, 18.3 +/- 2.9 dB, and 18.3 +/- 2.9 dB, respectively. At 1-day post NIHL, all groups demonstrated profound hearing loss. At 2 weeks, 2 and 10 uL Dex thresholds improved to 47.5 +/- 3.5 dB and 48.8 +/- 18.9 dB, respectively, whereas the untreated and saline groups remained unchanged. Mean cell counts in the cochlear nucleus (CN), superior olivary complex (SOC), and lateral lemniscus (LL) of control mice were 1483 +/- 190, 2807 +/- 67, and 112 +/- 20, respectively. After acoustic trauma, the untreated, saline, and 2 uL Dex groups yielded decreased neuronal counts in the SOC. In contrast, the 10 uL Dex group had 1883 +/- 186 (CN), 2774 +/- 182 (SOC), and 166 +/- 18 (LL). There was sporadic hair cell loss for all traumatized groups. CONCLUSION: Our NIHL mouse model demonstrated dose-dependent Dex pretreatment otoprotection against NIHL with preservation of retrocochlear auditory neurons. PMID- 25113509 TI - Preemptive submucosal infiltration with ropivacaine for uvulopalatopharyngoplasty. AB - OBJECTIVE: To evaluate the preemptive analgesic effect of submucosal infiltration of ropivacaine for uvulopalatopharyngoplasty. STUDY DESIGN: Randomized controlled trial. SETTING: Comprehensive clinical center and academic hospital. SUBJECTS AND METHODS: Fifty consecutive male patients scheduled for uvulopalatopharyngoplasty were divided randomly into group A and group B. In group A, 4 mL of 0.33% ropivacaine and normal saline with epinephrine was preincisionally injected under the mucosa on both sides of the tonsillar fossa, soft palate, and the lower part of palatoglossal arch, whereas the upper and middle parts of the palatoglossal arch and the upper part of the palatopharyngeal arch were infiltrated with 2 mL of the same mixture. In group B, an identical volume of normal saline with epinephrine was administered. In both groups, postoperative pain was initially controlled by intravenous morphine titration until patient-controlled analgesia with morphine could be used. Cumulative patient-controlled analgesic morphine consumption; visual analog scale scores at 4, 8, 12, 24, and 48 hours postoperatively at rest and during swallowing; and opioid-related adverse effects were recorded. RESULTS: The visual analog score was lower at rest during the 48 hour postoperative period and during swallowing within the first 12 hours for group A versus group B (P < .05). Patients in group A required 44.1%, 38.2%, and 41.1% less morphine during the first 24 hours, 24 hours to 48 hours, and 48 hours postoperatively, respectively, and fewer patients experienced nausea, vomiting, and pruritus (P < .05). CONCLUSION: Preemptive submucosal infiltration with 0.33% ropivacaine effectively controlled pain after uvulopalato-pharyngoplasty. PMID- 25113510 TI - Improving atrial fibrillation detection in patients with implantable cardiac devices by means of a remote monitoring and management application. AB - BACKGROUND: Atrial fibrillation (AF) is common in patients with cardiac implantable electronic devices (CIED) and has been associated with an increased stroke risk. The aim of our project was to assess the clinical value of a web based application, Discovery Link AFinder, in improving AF detection in CIED patients. METHODS AND RESULTS: Seven Italian hospitals performed an observational study consisting of four phases. During phase 1, expert nurses and cardiologists prospectively followed-up CIED patients via in-hospital examinations and remote monitoring, and classified clinically relevant events, particularly AF occurrence. During phase 2, Discovery Link AFinder was exploited to identify patients who had suffered AF in the previous 12 months through the systematic scanning of device data remote transmissions. Phases 3 and 4 were repetitions of phases 1 and 2, respectively, and were implemented 6 months after the previous phases. A total of 472 consecutive patients were included in phase 1; AF occurred in 170 patients, 61 of whom were identified as new AF patients. Evidence of AF during this phase prompted prescription of oral anticoagulation (OAC) therapy in 30 patients. In phase 2, AFinder uncovered new AF, unidentified in phase 1, in 54 patients and prompted implementation of OAC therapy in 11 patients. During phase 3, 30 new AF patients were identified by means of remote monitoring, while during phase 4, a further three AF patients were identified by AFinder only. CONCLUSIONS: The AFinder web-based software, applied on top of standard in hospital and remote monitoring, improved AF detection and enabled OAC treatment to be undertaken. PMID- 25113511 TI - Distribution of tension wood like gelatinous fibres in the roots of Acacia nilotica (Lam.) Willd. AB - KEY MESSAGE: The present study unravels the anatomical characteristics and distribution patterns of cell wall polymers in the G-fibres found in the roots of A. nilotica using different microscopy techniques (light, electron and immunofluorescence microscopy). The present study was aimed to investigate the anatomy of reaction xylem in the positively gravitropic roots of Acacia nilotica growing in compact and waterlogged soils. The roots collected from the two different sites showed occurrence of gelatinous fibres throughout xylem radii from a distance of 4 cm from the soil surface. The thickness of gelatinous layer (G-layer) increased in the root collected from the deeper soil. Further, the ultrastructural studies revealed a complete replacement of S2 and S3 layers in G fibres nearer to root tip region as compared to the root portion close to upper part of the soil surface. In addition, these fibres demonstrated intense lignification in compound middle lamellae region of G-fibre walls. Moreover, the vessel density and their width increased considerably near the root tip region. The immunofluorescence analysis suggested that the beta-1,4-galactans were prevalent in G-layer, whereas the xylan was restricted to only regions of lignified secondary wall. The similarities in distribution pattern and anatomical features of G-fibres in waterlogged and non-waterlogged roots suggest the occurrence of G-fibres as inherent characteristics in the roots of Acacia nilotica. PMID- 25113512 TI - Connection between expression of inducible nitric oxide synthase (iNOS) in skull base chordoma and lower urinary tract symptoms. AB - OBJECTIVE: To provide first insights into the potential role of iNOS expressed by skull base chordoma, which causes brainstem compression in and around Barrington's nucleus, and its effect on the micturition center. METHODS: Urodynamic testing of 22 symptomatic patients was performed. All women and men with skull base chordoma treated in two hospitals in Germany between 1986 and 2007 were studied. Lower urinary tract symptoms (LUTS) were documented in patients with acute brainstem compression due to local chordoma growth positive for iNOS expression. Brain magnetic resonance (MRI) images of the lesions of the symptomatic patients were performed. RESULTS: Of 74 treated patients, 22 (7 women, 15 men) with a median age of 37 years were evaluated with voiding diaries and computer urodynamic investigation. Urodynamic testing of 22 symptomatic patients with positive iNOS expression of skull base chordoma revealed detrusor overactivity in 55 %, low-compliance bladder in 14 %, detrusor sphincter dyssynergia in 45 % and uninhibited sphincter relaxation in 27 %. There was a significant correlation between strong iNOS expression (score 3-6) in skull base chordoma and severe urinary symptoms (p = 0.003, Spearman rho = 0.526). CONCLUSIONS: The expression of iNOS in skull base chordoma compressing the dorsolateral pons, in and around Barrington's nucleus, may influence the pontine micturition center (PMC) and be responsible for lower urinary tract symptoms. Nitric oxide may possibly act as a neurotransmitter. We assume that the high infiltration of chordoma with monocyte/macrophages enhances the release of nitric oxide, as monocyte/macrophages are the main source of iNOS. PMID- 25113513 TI - Incidence of pineal tumours. A review of the literature. AB - The knowledge of the incidence of pineal tumours is important not only for diagnostic care but also for its therapeutic programme. We reviewed the incidence of pineal tumours reported in literature in an attempt to establish if a difference existed between pineal gland tumours and the pineal region tumours as different authors use both expressions to indicate the same thing. The rate of frequency of these tumours is useful to guide the therapeutic choice for patients as the decisional tree is completely different for either germ cell tumours, pineal gland tumours or pineal gliomas and eventually papillary tumours of the pineal region. According to the French Register of pineal tumours, true pineal tumours represent: 27% pineal parenchymal tumours (PPT), 27% germ cell tumours, 17% gliomas, 8% papillary tumours. True pineal gland tumours are represented by: pineocytomas - (13%), pineal parenchymal tumours with intermediary differentiation PTT-ID - (66%) and pinealoblastomas - (21%). There was no statistical difference found between the French register and the Lyon series concerning histological diagnosis. It seemed to us important to discover its true incidence by comparing the data published in the literature and to stress the utility of the French Register for these uncommon tumours not only for recording new histological cases but also to document clinical symptomatology, therapeutic programmes, length of follow-up and clinical results for each patient treated. A better understanding of their natural history and improved evaluation of different treatments and their complications should contribute to improve clinical results. PMID- 25113514 TI - Review of environmental exposure concentrations of chemical warfare agent residues and associated the fish community risk following the construction and completion of the Nord Stream gas pipeline between Russia and Germany. AB - This paper compiles all the measured chemical warfare agent (CWA) concentrations found in relation to the Nord Stream pipeline work in Danish waters for the past 5 years. Sediment and biota sampling were performed along the pipeline route in four campaigns, prior to (in 2008 and 2010), during (in 2011) and after (in 2012) the construction work. No parent CWAs were detected in the sediments. Patchy residues of CWA degradation products of Adamsite, Clark I, phenyldichloroarsine, trichloroarsine and Lewisite II, were detected in a total of 29 of the 391 sediment samples collected and analyzed the past 5 years. The cumulative fish community risk quotient for the different locations, calculated as a sum of background and added risk, ranged between 0 and 0.017 suggesting a negligible acute CWA risk toward the fish community. The added risk from sediment disturbance in relation to construction of the pipelines represents less than 2% of the total risk in the areas with the highest calculated risk. The analyses of benthic infauna corroborate the finding of CWA related low risk across the years. There was no significant difference in CWA risk before (2008) and after the pipeline construction (2012). PMID- 25113515 TI - K4Nb6O17.4.5H2O: a novel dual functional material with quick photoreduction of Cr(VI) and high adsorptive capacity of Cr(III). AB - A series of orthorhombic phase K4Nb6O17.4.5H2O was synthesized via a hydrothermal approach. When presented in an acidic pH range, K4Nb6O17.4.5H2O showed a strong ability in quick reduction from Cr(VI) to Cr(III). The resulted Cr(III) ions were removed by an effective adsorption through simply adjusting the solution pH from strong acidity to near neutrality, owing to the sample's unique nano-sheet structure with a wide layer spacing. The Cr(III) ions adsorbed onto samples were released again for reusing by eluting with 1molL(-1) HCl solution, and K4Nb6O17.4.5H2O regenerated by immersing in a KOH solution. The reduction efficiency of Cr(VI) was still up to 98% after irradiation for 60min, and the removal efficiency of Cr(III) ions was as high as 83% even after five cycles. Therefore, K4Nb6O17.4.5H2O is clearly demonstrated to be an excellent dual functional material with quick photoreduction of Cr(VI) and high adsorptive capacity of Cr(III). The relevant materials reported herein might be found various environment-related applications. PMID- 25113516 TI - Iron amendments to reduce bioaccessible arsenic. AB - Former sugarcane lands on the Island of Hawaii have elevated levels of soil arsenic (As) from historical use of arsenical pesticides. The bioaccessible fraction of total As (AsTOT), a measure of the potential for human As uptake by incidental ingestion of soil, is used in the assessment of human health risk and the determination of the need for remedial action. Ferric chloride plus lime and ferrous sulfate plus lime were applied to As-contaminated soils in a field plot setting to determine the potential for reducing in vitro bioaccessible As (AsIVBA) by increasing As sequestration by the formation of additional iron (Fe) oxyhydroxides. The two Fe sources performed similarly in reducing AsIVBA over a 2 year observation period, with 30-41% reduction in AsIVBA for 0.25wt% Fe dosing (dry soil basis) and 59-63% reduction for 0.5wt% Fe dosing. Addition of phosphate (PO4) to treated and untreated soils caused a significant increase in AsIVBA. Iron-treated and control soils showed more than twice the AsIVBA after the addition of 1500mgPkg(-1). The cost of in situ treatment of As-contaminated soil with ferrous sulfate plus lime to lower AsIVBA was estimated to be an order of magnitude less than excavation and landfill disposal on the Island of Hawaii, making the technology a viable alternative when remedial action objectives were based on AsIVBA levels. PMID- 25113518 TI - The efficiency of quartz addition on electric arc furnace (EAF) carbon steel slag stability. AB - Electric arc furnace slag (EAF) has the potential to be re-utilized as an alternative to stone material, however, only if it remains chemically stable on contact with water. The presence of hydraulic phases such as larnite (2CaO SiO2) could cause dangerous elements to be released into the environment, i.e. Ba, V, Cr. Chemical treatment appears to be the only way to guarantee a completely stable structure, especially for long-term applications. This study presents the efficiency of silica addition during the deslagging period. Microstructural characterization of modified slag was performed by SEM and XRD analysis. Elution tests were performed according to the EN 12457-2 standard, with the addition of silica and without, and the obtained results were compared. These results demonstrate the efficiency of the inertization process: the added silica induces the formation of gehlenite, which, even in caustic environments, does not exhibit hydraulic behaviour. PMID- 25113517 TI - The critical role of the operating conditions on the Fenton oxidation of 2 chlorophenol: assessment of PCDD/Fs formation. AB - This work assesses the influence of the operating conditions H2O2 dose (20 or 100% of the stoichiometric amount), temperature (20 or 70 degrees C), and the presence of chloride in the oxidation medium in the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during Fenton treatment of aqueous samples of 2-chlorophenol, 2-CP, one of the strongest precursor of PCDD/Fs. After 4h of oxidation in the experiments carried out with 20% H2O2 chlorinated phenoxyphenols and biphenyls, which are intermediates in PCDD/Fs formation, as well as PCDD/Fs were observed, resulting in concentrations 11 times higher than in the untreated sample. Additionally, when NaCl was also present in the reaction medium, PCDD/Fs were formed at higher extent, with a total concentration 74.4 times higher than in the untreated 2-CP solution. Results depicted a preferential formation of PCDFs over PCDDs, with dominance of lower chlorinated PCDD/Fs (tetra and penta-PCDD/Fs). Besides, the formation of the most toxic PCDD/Fs congeners (2,3,7,8-PCDD/Fs) was not favored under the operating conditions used in this work. PMID- 25113519 TI - The effects of dexmedetomidine administration on the pulmonary artery pressure and the transpulmonary pressure gradient after the bidirectional superior cavopulmonary shunt. AB - The hemodynamic effects of dexmedetomidine (DEX) on pulmonary artery pressure (PAP) are not fully understood in patients with a single-ventricle physiology. The objective of this retrospective study was to characterize the effect of perioperative DEX infusion on PAP and the transpulmonary pressure gradient after a bidirectional superior cavopulmonary shunt (BCPS) operation. We retrieved physiologic data including the heart rate, incidence of cardiac pacing, systolic and diastolic arterial blood pressure (ABP), and superior vena cava (SVC) and inferior vena cava (IVC) pressures from the medical records of all patients <12 months of age who underwent a BCPS operation. Patients with an additional Norwood or Damus-Kaye-Stansel procedure, those with additional pulmonary blood flow, and those without both a SVC and an IVC catheter were excluded from the present study. Following the BCPS operation, the SVC pressure is equivalent to the PAP. Similarly, the IVC pressure is equivalent to the common atrial pressure (CAP). Accordingly, we can directly assess the transpulmonary pressure gradient, defined as the difference between the PAP and the CAP, using simultaneous SVC and IVC pressure measurements. Twenty-nine patients were included in the present study. We did not find any increase in the PAP, CAP, PAP/systolic ABP ratio, or the transpulmonary pressure gradient as of 6 h after admission to the intensive care unit when the patients were treated with DEX infusion at a median (interquartile ranges) dose of 0.6 mcg/kg/h (0.4, 0.64 mcg/kg/h). We concluded that the administration of DEX to children with a single-ventricle physiology is acceptable. PMID- 25113520 TI - Development of a charge adjustment model for cardiac catheterization. AB - A methodology that would allow for comparison of charges across institutions has not been developed for catheterization in congenital heart disease. A single institution catheterization database with prospectively collected case characteristics was linked to hospital charges related and limited to an episode of care in the catheterization laboratory for fiscal years 2008-2010. Catheterization charge categories (CCC) were developed to group types of catheterization procedures using a combination of empiric data and expert consensus. A multivariable model with outcome charges was created using CCC and additional patient and procedural characteristics. In 3 fiscal years, 3,839 cases were available for analysis. Forty catheterization procedure types were categorized into 7 CCC yielding a grouper variable with an R (2) explanatory value of 72.6%. In the final CCC, the largest proportion of cases was in CCC 2 (34%), which included diagnostic cases without intervention. Biopsy cases were isolated in CCC 1 (12%), and percutaneous pulmonary valve placement alone made up CCC 7 (2%). The final model included CCC, number of interventions, and cardiac diagnosis (R (2) = 74.2%). Additionally, current financial metrics such as APR DRG severity of illness and case mix index demonstrated a lack of correlation with CCC. We have developed a catheterization procedure type financial grouper that accounts for the diverse case population encountered in catheterization for congenital heart disease. CCC and our multivariable model could be used to understand financial characteristics of a population at a single point in time, longitudinally, and to compare populations. PMID- 25113521 TI - Effect of hypercrosslinking conditions on pore size distribution and efficiency of monolithic stationary phases. AB - Three dihalogenic solvents differing in the length of alkyl chain (1,2 dichloroethane, 1,4-dichlorobutane, and 1,6-dichlorohexane) with three Friedel Crafts alkylation catalysts varying in reactivity (AlCl3 , FeCl3 , and SnCl4 ) have been used to prepare hypercrosslinked poly(styrene-co-vinylbenzyl chloride co-divinylbenzene) columns. Hydrodynamic characteristics as well as column efficiency and mass transfer resistance were tuned by the combination of swelling solvent and alkylation reaction catalyst in the modification mixture. The column swelled in 1,6-dichlorohexane and hypercrosslinked in the presence of AlCl3 provided the highest column efficiency and enabled fast isocratic separations of small molecules in a RP mode. To uncover factors controlling the efficiency of hypercrosslinked monolithic columns, we have studied pore volume distribution of prepared columns. We found that column efficiency increases with the higher pore volume of pores smaller than 2 nm. PMID- 25113522 TI - A combined high CYP2D6-CYP2C19 metabolic capacity is associated with the severity of suicide attempt as measured by objective circumstances. AB - This study examined, for the first time, whether a high CYP2D6-CYP2C19 metabolic capacity combination increases the likelihood of suicidal intent severity in a large study cohort. Survivors of a suicide attempt (n=587; 86.8% women) were genotyped for CYP2C19 (*2, *17) and CYP2D6 (*3, *4, *4xN, *5, *6, *10, wtxN) genetic variation and evaluated with the Beck Suicide Intent Scale (SIS). Patients with a high CYP2D6-CYP2C19 metabolic capacity showed an increased risk for a severe suicide attempt (P<0.01) as measured by the SIS-objective circumstance subscale (odds ratio (OR)=1.37; 95% confidence interval (CI)=1.05 1.78; P=0.02) after adjusting for confounders (gender, age, level of studies, marital status, mental disorders, tobacco use, family history of suicide, personal history of attempts and violence of the attempt). Importantly, the risk was greater in those without a family history of suicide (OR=1.82; CI=1.19-2.77; P=0.002). Further research is warranted to evaluate whether the observed relationship is mediated by the role of CYP2D6 and CYP2C19 involvement in the endogenous physiology or drug metabolism or both. PMID- 25113523 TI - Societal cost-of-illness in patients with borderline personality disorder one year before, during and after dialectical behavior therapy in routine outpatient care. AB - Societal cost-of-illness in a German sample of patients with borderline personality disorder (BPD) was calculated for 12 months prior to an outpatient Dialectical Behavior Therapy (DBT) program, during a year of DBT in routine outpatient care and during a follow-up year. We retrospectively assessed resource consumption and productivity loss by means of a structured interview. Direct costs were calculated as opportunity costs and indirect costs were calculated according to the Human Capital Approach. All costs were expressed in Euros for the year 2010. Total mean annual BPD-related societal cost-of-illness was ?28026 (SD = ?33081) during pre-treatment, ?18758 (SD = ?19450) during the DBT treatment year for the 47 DBT treatment completers, and ?14750 (SD = ?18592) during the follow-up year for the 33 patients who participated in the final assessment. Cost savings were mainly due to marked reductions in inpatient treatment costs, while indirect costs barely decreased. In conclusion, our findings provide evidence that the treatment of BPD patients with an outpatient DBT program is associated with substantial overall cost savings. Already during the DBT treatment year, these savings clearly exceed the additional treatment costs of DBT and are further extended during the follow-up year. Correspondingly, outpatient DBT has the potential to be a cost-effective treatment for BPD patients. Efforts promoting its implementation in routine care should be undertaken. PMID- 25113525 TI - Prevalence, correlates, and comorbidities of DSM-IV psychiatric disorders in children in Seoul, Korea. AB - The present study reports past-year prevalence of and comorbidities associated with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) disorders in 1645 children aged 6 to 12 years in Seoul, Korea. The diagnosis was based on the parental version of the Diagnostic Interview Schedule for Children (DISC-IV). Our participants completed the Children's Depression Inventory (CDI). The estimated prevalence of any full-syndrome and subthreshold DSM-IV disorders were 16.2% and 28.1%, respectively. The most prevalent disorders were specific phobia (9.6%), attention-deficit hyperactivity disorder (ADHD; 5.9%), and oppositional defiant disorder (ODD; 4.9%). The estimated prevalence of depressive disorder was 0.1% according to the DISC-IV and1.9% according to the CDI. ADHD, ODD, and anxiety disorders were highly comorbid. Our study highlights the importance of obtaining children's self-report data in addition to the parents' interview, particularly for depression, and the importance of early detection of subthreshold conditions and considering comorbid diagnoses. PMID- 25113526 TI - The impact of the environment on health in Mongolia: a systematic review. AB - Mongolia has significant exposure to environmental risk factors because of poor environmental management and behaviors, and children are increasingly vulnerable to these threats. This study aimed to assess levels of exposure and summarize the evidence for associations between exposures to environmental risk factors and adverse health outcomes in Mongolia, with a particular focus on children. A systematic review was conducted using the PubMed, EMBASE, Web of Science, Global Health Library, CINAHL, CABI, Scopus, and mongolmed.mn electronic databases up to April 2014 . A total of 59 studies meeting the predetermined criteria were included. Results indicate that the Mongolian population has significant exposure to outdoor and indoor air pollution, metals, environmental tobacco smoke, and other chemical toxins, and these risk factors have been linked to respiratory and cardiovascular diseases among adults and respiratory diseases and neurodevelopmental disorders among children. Well-designed epidemiological investigations in vulnerable populations especially in pregnant women and children are recommended. PMID- 25113524 TI - A randomized controlled trial of an internet-based therapist-assisted indicated preventive intervention for prolonged grief disorder. AB - This trial assessed the feasibility, acceptability, tolerability, and efficacy of an Internet-based therapist-assisted cognitive-behavioral indicated prevention intervention for prolonged grief disorder (PGD) called Healthy Experiences After Loss (HEAL). Eighty-four bereaved individuals at risk for PGD were randomized to either an immediate treatment group (n = 41) or a waitlist control group (n = 43). Assessments were conducted at four time-points: prior to the wait-interval (for the waitlist group), pre-intervention, post-intervention, 6 weeks later, and 3 months later (for the immediate group only). Intent-to-treat analyses indicated that HEAL was associated with large reductions in prolonged grief (d = 1.10), depression (d = .71), anxiety (d = .51), and posttraumatic stress (d = .91). Also, significantly fewer participants in the immediate group met PGD criteria post-intervention than in the waitlist group. Pooled data from both groups also yielded significant reductions and large effect sizes in PGD symptom severity at each follow-up assessment. The intervention required minimal professional oversight and ratings of satisfaction with treatment and usability of the Internet interface were high. HEAL has the potential to be an effective, well tolerated tool to reduce the burden of significant pre-clinical PGD. Further research is needed to refine HEAL and to assess its efficacy and mechanisms of action in a large-scale trial. PMID- 25113527 TI - Efavirenz modulation of sleep spindles and sleep spectral profile. AB - Non-nucleoside reverse transcriptase inhibitors are important antiretroviral agents for the treatment of human immunodeficiency virus. Some non-nucleoside reverse transcriptase inhibitors, in particular efavirenz, have prominent effects on sleep, cognition and psychiatric variables that limit their tolerability. To avoid confounds due to drug-drug and drug-disease interactions, we assessed the effects of efavirenz in healthy volunteers on sleep, cognition and psychological endpoints during the first week of treatment. Forty healthy male subjects were randomized to receive placebo or efavirenz 600 mg nightly for 7 days after completion of a 3-day placebo run-in period. Treatment with efavirenz was associated with reduced time to sleep onset in the Maintenance of Wakefulness Test, an increase in non-rapid eye movement sleep, a large exposure-related decrease in sigma band spectral density and sleep spindle density during non rapid eye movement sleep, and reduced performance on an attention switching task. Because efavirenz has been shown to have serotonin 2A receptor partial-agonist properties, we reasoned that antagonism of serotonin 2A receptor signalling in the thalamic reticular nucleus, which generates sleep spindles and promotes attention, may be responsible. Consistent with predictions, treatment of healthy volunteers with a single dose of a serotonin 2A receptor antagonist was found to significantly suppress sigma band spectral density in an exposure-related manner and modulated the overall spectral profile in a manner highly similar to that observed with efavirenz, consistent with the notion that efavirenz exhibits serotonin 2A receptor partial-agonist pharmacology in humans. PMID- 25113531 TI - Rapid progression of perianal abscess into Fournier's gangrene. PMID- 25113528 TI - Quality of life among people living with hypertension in a rural Vietnam community. AB - BACKGROUND: To respond to growing prevalence of hypertension in Vietnam, it is critical to have an in-depth understanding about quality of life (QOL) among people living with hypertension and related factors. This study aimed to measure QOL among hypertensive people in a rural community in Vietnam, and its association with socio-demographic characteristics and factors related to treatment. METHODS: This study was conducted in a rural community located 60 km from Ho Chi Minh City. Face-to-face interviews were conducted among 275 hypertensive people aged 50 years and above using WHOQOL-BREF questionnaire. Descriptive statistics were used to examine mean scores of quality of life. Cronbach's alpha coefficient and Pearson's correlation coefficient were applied to estimate the internal consistency, and the level of agreement between different domains of WHOQOL-BREF, respectively. Independent T-test and ANOVA test followed by multiple linear regression analyses were used to measure the association between QOL domains and independent variables. RESULTS: Both overall WHOQOL-BREF and each domain had a good internal consistency, ranging from 0.65 to 0.88. The QOL among hypertensive patients was found moderate in all domains, except for psychological domain that was fairly low (mean = 49.4). Backward multiple linear regressions revealed that being men, married, attainment of higher education, having physical activities at moderate level, and adherence to treatment were positively associated with QOL. However, older age and presence of co-morbidity were negatively associated with QOL. CONCLUSION: WHOQOL-BREF is a reliable instrument to measure QOL among hypertensive patients. The results revealed low QOL in psychological domain and inequality in QOL across socio demographic characteristics. Given the results, encouraging physical activities and strengthening treatment adherence should be considered to improve QOL of hypertensive people, especially for psychological aspect. Actions to improve QOL among hypertensive patients targeted towards women, lower educated and unmarried patients are needed in the setting. PMID- 25113533 TI - Special issue on "Oxidative stress and mitochondrial alterations in aging and disease". PMID- 25113532 TI - Infection with human rhinovirus 16 promotes enhanced IgE responsiveness in basophils of atopic asthmatics. AB - BACKGROUND: Rhinovirus and IgE act in concert to promote asthma exacerbations. While basophils are the principal cell type in the blood that is activated by IgE, their role in virus-induced asthma episodes remains elusive. OBJECTIVE: To monitor IgE responsiveness in circulating basophils of rhinovirus-infected atopic asthmatics during acute infection and convalescence. METHODS: The capacity for basophils to respond to IgE was assessed by testing the effects of allergen, or cross-linking anti-FcepsilonRI and anti-IgE antibodies, on surface TSLP receptor in 24-hour PBMC cultures. Activation profiles of basophils from atopic asthmatics challenged intranasally with human rhinovirus 16 were monitored directly ex vivo or else in 24-hour cultures, at baseline (day 0), and then at days 4 and 21 post challenge. RESULTS: Basophils in atopic asthmatics, but not in non-atopic controls, upregulated TSLP receptor upon IgE receptor ligation. The magnitude of this response was correlated with the proportion of serum total IgE that was allergen-specific (r = 0.615, P < 0.05). Following rhinovirus infection, all subjects developed nasal symptoms that peaked 3-5 days after viral challenge. Basophils displayed maximal IgE responsiveness 3 weeks post-challenge as judged by TSLP receptor levels in 24-hour cultures. No significant change in total IgE or specific IgE antibodies was detected during rhinovirus infection. By contrast, levels of IgE receptor-associated spleen tyrosine kinase, Syk, were increased on day 4 (P < 0.05), and elevated levels were also detected three weeks post challenge. CONCLUSIONS AND CLINICAL RELEVANCE: Circulating basophils display increased IgE responsiveness 3 weeks after rhinovirus infection in atopic asthmatics. This observation, coupled with increased expression of Syk, implicates basophils in promoting, or else prolonging, rhinovirus-induced inflammation in atopic asthmatics. PMID- 25113535 TI - Improved synthesis of [(18)F]FLETT via a fully automated vacuum distillation method for [(18)F]2-fluoroethyl azide purification. AB - The synthesis of [(18)F]2-fluoroethyl azide and its subsequent click reaction with 5-ethynyl-2'-deoxyuridine (EDU) to form [(18)F]FLETT was performed using an iPhase FlexLab module. The implementation of a vacuum distillation method afforded [(18)F]2-fluoroethyl azide in 87+/-5.3% radiochemical yield. The use of Cu(CH3CN)4PF6 and TBTA as catalyst enabled us to fully automate the [(18)F]FLETT synthesis without the need for the operator to enter the radiation field. [(18)F]FLETT was produced in higher overall yield (41.3+/-6.5%) and shorter synthesis time (67min) than with our previously reported manual method (32.5+/ 2.5% in 130min). PMID- 25113536 TI - Excel2Genie: A Microsoft Excel application to improve the flexibility of the Genie-2000 Spectroscopic software. AB - Excel2Genie, a simple and user-friendly Microsoft Excel interface, has been developed to the Genie-2000 Spectroscopic Software of Canberra Industries. This Excel application can directly control Canberra Multichannel Analyzer (MCA), process the acquired data and visualize them. Combination of Genie-2000 with Excel2Genie results in remarkably increased flexibility and a possibility to carry out repetitive data acquisitions even with changing parameters and more sophisticated analysis. The developed software package comprises three worksheets: display parameters and results of data acquisition, data analysis and mathematical operations carried out on the measured gamma spectra. At the same time it also allows control of these processes. Excel2Genie is freely available to assist gamma spectrum measurements and data evaluation by the interested Canberra users. With access to the Visual Basic Application (VBA) source code of this application users are enabled to modify the developed interface according to their intentions. PMID- 25113534 TI - Microscopy and genomic analysis of Mycoplasma parvum strain Indiana. AB - Mycoplasma parvum [Eperythrozoon parvum] is the second hemotrophic mycoplasma (hemoplasma) described in pigs. Unlike M. suis, its closest phylogenetic relative, M. parvum, is considered a non-pathogenic bacterium in this host species. Natural infection of a domestic, 6-month-old splenectomized pig with M. parvum strain Indiana is described herein. Light and scanning electron microscopy of the bacteria were performed in addition to whole genome sequencing, analysis, and comparison to the genome of M. suis strain Illinois. Neither clinical signs nor anemia were observed during the infection. Microscopy analyses revealed coccoid to rod- shaped organisms varying from 0.2 to 0.5 MUm; they were observed individually or in short chains by both light and electron microscopy, however less than 30% of the red blood cells were infected at peak bacteremia. The single circular chromosome of M. parvum was only 564 395 bp, smaller than M. genitalium, previously considered the tiniest member of the Mollicutes. Its general genomic features were similar to others in this class and species circumscription was verified by phylogenomic analysis. A gene-by-gene comparison between M. suis and M. parvum revealed all protein coding sequences (CDS) with assigned functions were shared, including metabolic functions, transporters and putative virulence factors. However, the number of CDS in paralogous gene families was remarkably different with about half as many paralogs in M. parvum. The differences in paralogous genes may be implicated in the different pathogenic potential of these two species, however variable gene expression may also play a role. Both are areas of ongoing investigation. PMID- 25113537 TI - A semi-empirical approach to analyze the activities of cylindrical radioactive samples using gamma energies from 185 to 1764 keV. AB - This work suggests a method for determining the activities of cylindrical radioactive samples. The self-attenuation factor was applied for providing the self-absorption correction of gamma rays in the sample material. The experimental measurement of a (238)U reference sample and the calculation using the MCNP5 code allow obtaining the semi-empirical formulae of detecting efficiencies for the gamma energies ranged from 185 to 1764keV. These formulae were used to determine the activities of the (238)U, (226)Ra, (232)Th, (137)Cs and (40)K nuclides in the IAEA RGU-1, IAEA-434, IAEA RGTh-1, IAEA-152 and IAEA RGK-1 radioactive standards. The coincidence summing corrections for gamma rays in the (238)U and (232)Th series were applied. The activities obtained in this work were in good agreement with the reference values. PMID- 25113538 TI - [Tuberculosis, "a sustainable challenge"]. PMID- 25113540 TI - Species identification of strains belonging to genus Citrobacter using the biochemical method and MALDI-TOF mass spectrometry. AB - Strains of genus Citrobacter (152 isolates from 1950 to 1988 deposited in the Czech National Collection of Type Cultures, Prague) were re-classified using biological and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) methods. One-hundred thirty-six strains (ca. 90 %) were identified to the species level using the biological method with evaluation by Farmer matrix. MALDI-TOF MS exhibited better identification capability, the data being more compact; the method was unambiguously successful in typing 145 (95 %) strains. Comparison of the results of identification by the two methods revealed differences (for 12 samples) in identified species which, considering all biochemical and/or MS characteristics, could be attributed to the natural variability of strains and close relation of the misidentified species (all of them belonged to the Citrobacter freundii complex). Taking into account all the above data, both methods can be considered reliable; however, the MALDI-TOF MS exhibits higher accuracy, efficiency, and rapidity. PMID- 25113541 TI - Variation in riparian consumer diet composition and differential bioaccumulation by prey influence the risk of exposure to elements from a recently remediated fly ash spill. AB - Emerging aquatic insects play a key role in transporting aquatic nutrients and contaminants to riparian consumers. However, little is known about how within- and between-year variation in the diet or patterns of element bioaccumulation in emerging insect taxa may influence the risk of exposure to wildlife. During 2 breeding seasons, the composition of the diet of tree swallows (Tachycineta bicolor) was examined at several colonies that were exposed to element contamination from a remediated coal fly ash spill to determine how variation in the diet influenced the risk of exposure to elements. The proportion of the diet that consisted of insects with an aquatic larval stage was positively related to concentrations of As, Fe, Se, and Tl in the samples. The proportion of the diet that consisted of Chironomidae (midges) was positively related to exposure to these elements at most colonies within and between years. Ephemeroptera (mayflies) contained higher concentrations of Se than midges, including 17 samples with concentrations of Se above 5 ug/g dry mass, the threshold of toxicological concern for birds. This was even the case at colonies several kilometers downstream from the spill. The results indicate that greater consideration should be given to the pattern of element bioaccumulation among different prey taxa and their relative importance in the diet to better assess the risk of contaminant exposure. PMID- 25113539 TI - Genetics of Alzheimer's disease. AB - The analyses of genetic factors contributing to Alzheimer's disease (AD) and other dementias have evolved at the same pace as genetic and genomic technologies are developed and improved. The identification of the first genes involved in AD arose from family-based studies, but risk factors have mainly been identified by studies comparing groups of patients with groups of controls. The best outcomes have been heavily associated with the capacity of interrogating genetic variability at the genome level without any particular a priori hypothesis. In this review we assess the role of genetic family studies in Alzheimer's disease and other dementias within the current status of dementias' and, particularly, AD's genetic architecture. PMID- 25113542 TI - Mechanical bowel obstruction due to occlusion with a biliary calculus: a case of a 91-year-old woman with nausea and vomiting. PMID- 25113543 TI - Molecular characterization of rice sphingosine-1-phosphate lyase gene OsSPL1 and functional analysis of its role in disease resistance response. AB - KEY MESSAGE: Our results indicate that overexpression of OsSPL1 in transgenic tobacco plants attenuated disease resistance and facilitated programmed cell death. Long-chain base phosphates including sphingosine-1-phosphate have been shown to act as signaling mediators in regulating programmed cell death (PCD) and stress responses in mammals. In the present study, we characterized a rice gene OsSPL1, encoding a putative sphingosine-1-phosphate lyase that is involved in metabolism of sphingosine-1-phosphate. Expression of OsSPL1 was down-regulated in rice plants after treatments with salicylic acid, benzothiadiazole and 1-amino cyclopropane-1-carboxylic acid, but was induced by infection with a virulent strain of Magnaporthe oryzae, the causal agent of rice blast disease. Transgenic tobacco lines with overexpression of OsSPL1 were generated and analyzed for the possible role of OsSPL1 in disease resistance response and PCD. The OsSPL1 overexpressing tobacco plants displayed increased susceptibility to infection of Pseudomonas syringae pv. tabaci (Pst), the causal agent of wildfire disease, showing severity of disease symptom and bacterial titers in inoculated leaves, and attenuated pathogen-induced expression of PR genes after infection of Pst as compared to the wild-type and vector-transformed plants. Higher level of cell death, as revealed by dead cell staining, leakage of electrolyte and expression of hypersensitive response indicator genes, was observed in the OsSPL1 overexpressing plants after treatment with fumonisin B1, a fungal toxin that induces PCD in plants. Our results suggest that OsSPL1 has different functions in regulating disease resistance response and PCD in plants. PMID- 25113546 TI - Single-cell transcriptome in the identification of disease biomarkers: opportunities and challenges. AB - Single cell transcriptome defined as the entire RNA or polyadenylated products of RNA polymerase II on a cell can describe the gene regulation networks responsible for physiological functions, behaviours, and phenotypes in response to signals and microenvironmental changes. Single cell transcriptome/sequencing has the special power to investigate small groups of differentiating cells, circulating tumour cells, or tissue stem cells. A large number of factors may influence the extent of single-cell heterogeneity within a system. It is the opportunity that the single-cell sequencing can be used for the identification of genetic changes in rare cells, e.g. cancer and tissue stem cells, in clinical samples. The methodologies of single-cell sequencing have been improved and developed with the increase of the understanding and attention. The clinical research and application of the single cell sequencing analysis are expected to identify and validate disease-specific biomarkers, network biomarkers, dynamic network biomarkers. The single cell research and value will be also dependent upon the understanding of genomic heterogeneity, planning and design of study protocol, representative of selected and targeted cells, and sensitivity and repeatability of the methodology. The single cell sequencing can be used to develop new diagnostics, monitor disease progresses, measure responses to therapies, and predict the prognosis of patients, although there are still a large number of challenges and difficulties to be faced. It would be more values and specificities of the single cell sequencing to integrate with the function of cells, organs, and systems of the body, the clinical phenotypes of patients, and the description of clinical bioinformatics. PMID- 25113544 TI - Molecular and physiological stages of priming: how plants prepare for environmental challenges. AB - Being sessile organisms, plants must respond to various challenges in the environment. The priming process consists of three clear stages. The first stage includes all the cellular changes in the absence of the challenge so-called pre challenge priming stage. These changes are expected to be rather subtle, affecting the preparation of the plant to properly manage subsequent responses to pathogens with no major fitness costs. Most of the research that has been conducted at this stage has been dedicated to the study of changes in gene expression and protein phosphorylation. However, the metabolic changes that occur during the pre-challenge priming stage are poorly understood. The second stage affects the early to late stages of the defence response, which occurs after the interaction with a pathogen has been established. Most studies involving priming are dedicated to the molecular events that take place during this stage. Most studies have shown that defence priming is strongly hormonally regulated; however, there is also evidence of the involvement of phenolic derivative compounds and many other secondary metabolites, leading to stronger and faster plant responses. The third priming phase ranges from long lasting defence priming to trans-generational acquired resistance. Long-term metabolic transitions, that occur in the offspring of primed plants, remain to be elucidated. Here we review existing information in the literature that relates to the metabolic changes that occur during all three defence priming stages and highlight the metabolic transitions that are associated with the stimulation of priming and the characteristics of the pathogens whenever possible. PMID- 25113548 TI - [Concordance between central venous and arterial blood gases in post-surgical myocardial revascularization patients in stable condition]. AB - OBJECTIVE: The concordance between the parameters of arterial and central venous blood gases has not been defined yet. We studied the concordance between both parameters in post-surgical myocardial revascularization patients in stable condition. METHODS: Consecutive subjects were studied in a cross-sectional design. The position of the central venous catheter was performed and simultaneously we obtained arterial and central venous blood samples prior to discharge from the intensive care unit. Data are expressed according to Bland Altman statistical method and the intraclass correlation coefficient. Statistical result was accepted at P<.05. RESULTS: Two hundred and six samples were studied of 103 post-surgical patients, pH and lactate had a mean difference (limits of agreement) 0.029+/-0.048 (-0018, 0.077) and -0.12+/-0.22 (-0.57, 0.33) respectively. The magnitude of the intraclass correlation coefficient was 0.904 and 0.943 respectively. The values related to oxygen pressure were 27.86+/-6.08 (15.9, 39.8) and oxygen saturation 33.02+/-6.13 (21, 45), with magnitude of 0.258 and 0.418 respectively. CONCLUSION: The best matching parameters between arterial and central venous blood samples were pH and lactate. PMID- 25113549 TI - Preparation, biodistribution, and scintigraphic evaluation of (99m)Tc clindamycin: an infection imaging agent. AB - Bacterial infection is found to be the cause of death throughout the world. Nuclear medicine imaging with the help of radiopharmaceuticals has great potential for treating infections. In the present work, clindamycin, a lincosamide antibiotic, was labeled with technetium-99 m (~380 MBq). Clindamycin has been proven to be efficient for treating serious infections caused by bacteria such as Staphylococcus aureus. Quality control, characterization, biodistribution, and scintigraphy of radiolabeled clindamycin were done, and labeling efficiency was determined by ascending paper chromatography. More than 95 % labeling efficiency with technetium-99 m ((99m)Tc) was achieved at pH 6-7 while using 2.5-3 MUg SnCl2 . H2O as a reducing agent and 100 MUg of ligand at room temperature. The characterization of the compound was performed by using electrophoresis, HPLC and shake flask assay. Electrophoresis indicates the neutral behavior of (99m)Tc-clindamycin. HPLC analysis confirms the single specie of the labeled compound, while shake flask assay confirms high lipophilicity. The biodistribution studies of (99m)Tc-clindamycin were performed Sprague Dawley rats bearing bacterial infection. Scintigraphy and biodistribution studies showed a high uptake of (99m)Tc-clindamycin in the liver, heart, lung, and stomach as well as at S. aureus-infected sites in rabbits. PMID- 25113547 TI - Digging a little deeper: the stages of invadopodium formation and maturation. AB - Invadopodia are actin-rich protrusions that degrade the extracellular matrix and are required for penetration through the basement membrane, stromal invasion and intravasation. Invadopodia are enriched in actin regulators, such as cortactin, cofilin, N-WASp, Arp2/3 and fascin. Much of the work to date has centered around identifying the proteins involved in regulating actin polymerization and matrix degradation. Recently, there have been significant advances in characterization of the very early stages of invadopodium precursor assembly and the role of adhesion proteins, such as beta1 integrin, talin, FAK and Hic-5, in promoting invadopodium maturation. This review summarizes these findings in the context of our current model of invadopodial function and highlights some of the important unanswered questions in the field. PMID- 25113550 TI - Bioremediation of distillery sludge into soil-enriching material through vermicomposting with the help of Eisenia fetida. AB - The aim of the present study was bioremediation of distillery sludge into a soil enriching material. It was mixed with a complementary waste, cattle dung, and subjected to vermicomposting with (V) and without (T, control) Eisenia fetida in the ratio of 0:100 % (V1, T1), 10:90 (V2, T2), 25:75 (V3, T3), 50:50 (V4, T4), 75:25 (V5, T5) and 100:0 % (V6, T6), respectively. Survival rate, growth rate, onset of maturity, cocoon production and population build-up increased with increasing ratio of cattle dung. Maximum mortality of earthworm was observed in V6 mixture. On the basis of response surface design, the concentration of sludge giving highest number of worms, cocoons and hatchlings came out to be 21.11, 24.51 and 17.19 %, respectively. Nitrogen, phosphorus, sodium and pH increased during vermicomposting but decreased in the products without earthworm and there was increase in the contents of transition metals in the products of both the techniques. However, organic carbon, electrical conductivity and potassium showed an opposite trend. PMID- 25113551 TI - Impact of xylan on synergistic effects of xylanases and cellulases in enzymatic hydrolysis of lignocelluloses. AB - Supplementation of xylanase (XYL) has been found to synergistically improve the performance of cellulases (CEL) in the hydrolysis of lignocelluloses. However, the effect of xylan on the synergistic effects of XYL and CEL is still unclear. In this work, the effect of xylan on the synergy between CEL and XYL was investigated. Xylan content in corn stover was generally a good indicator of the degree of the synergism between CEL and XYL. Strongest synergism was observed in the hydrolysis of cellulose in corn stover with the highest xylan contents. A more evident synergistic effect of CEL in xylan hydrolysis was observed in the substrates with low original xylan content. It was also found that the ratio of cellulose to xylan in substrates correlated to the synergism between the two types of enzymes. The results indicated that supplementation of XYL with CEL was most effective in the hydrolysis of corn stover with the highest xylan content. For efficient enzymatic hydrolysis of lignocelluloses, both cellulases and xylanase were important because cellulose and xylan coved each other and these enzymes could improve their performance each other in the hydrolysis of cellulose and xylan in lignocelluloses. PMID- 25113552 TI - Fluidized bed layer-by-layer microcapsule formation. AB - Polymer microcapsules can be used as bioreactors and artificial cells; however, preparation methods for cell-like microcapsules are typically time-consuming, low yielding, and/or involve custom microfluidics. Here, we introduce a rapid (~30 min per batch, eight layers), scalable (up to 500 mg of templates), and efficient (98% yield) microcapsule preparation technique utilizing a fluidized bed for the layer-by-layer (LbL) assembly of polymers, and we investigate the parameters that govern the formation of robust capsules. Fluidization in water was possible for particles of comparable diameter to mammalian cells (>5 MUm), with the experimental flow rates necessary for fluidization matching well with the theoretical values. Important variables for polymer film deposition and capsule formation were the concentration of polymer solution and the molecular weight of the polymer, while the volume of the polymer solution had a negligible impact. In combination, increasing the polymer molecular weight and polymer solution concentration resulted in improved film deposition and the formation of robust microcapsules. The resultant polymer microcapsules had a thickness of ~5.5 nm per bilayer, which is in close agreement with conventionally prepared (quiescent (nonflow) adsorption/centrifugation/wash) LbL capsules. The technique reported herein provides a new way to rapidly generate microcapsules (approximately 8 times quicker than the conventional means), while being also amenable to scale-up and mass production. PMID- 25113553 TI - Contraceptive confidence and timing of first birth in Moldova: an event history analysis of retrospective data. AB - OBJECTIVES: To test the contraceptive confidence hypothesis in a modern context. The hypothesis is that women using effective or modern contraceptive methods have increased contraceptive confidence and hence a shorter interval between marriage and first birth than users of ineffective or traditional methods. We extend the hypothesis to incorporate the role of abortion, arguing that it acts as a substitute for contraception in the study context. SETTING: Moldova, a country in South-East Europe. Moldova exhibits high use of traditional contraceptive methods and abortion compared with other European countries. PARTICIPANTS: Data are from a secondary analysis of the 2005 Moldovan Demographic and Health Survey, a nationally representative sample survey. 5377 unmarried women were selected. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure was the interval between marriage and first birth. This was modelled using a piecewise-constant hazard regression, with abortion and contraceptive method types as primary variables along with relevant sociodemographic controls. RESULTS: Women with high contraceptive confidence (modern method users) have a higher cumulative hazard of first birth 36 months following marriage (0.88 (0.87 to 0.89)) compared with women with low contraceptive confidence (traditional method users, cumulative hazard: 0.85 (0.84 to 0.85)). This is consistent with the contraceptive confidence hypothesis. There is a higher cumulative hazard of first birth among women with low (0.80 (0.79 to 0.80)) and moderate abortion propensities (0.76 (0.75 to 0.77)) than women with no abortion propensity (0.73 (0.72 to 0.74)) 24 months after marriage. CONCLUSIONS: Effective contraceptive use tends to increase contraceptive confidence and is associated with a shorter interval between marriage and first birth. Increased use of abortion also tends to increase contraceptive confidence and shorten birth duration, although this effect is non linear-women with a very high use of abortion tend to have lengthy intervals between marriage and first birth. PMID- 25113554 TI - Long-term follow-up results in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents: results from a single high-volume PCI centre. AB - OBJECTIVE: To assess both short-term and long-term prognosis in consecutive patients with coronary heart disease treated with drug-eluting stents in a high volume percutaneous coronary intervention (PCI) centre. DESIGN: Observational cohort study. SETTING: A hospital in the Henan province, China, between 2009 and 2011. PARTICIPANTS: A total of 2533 patients were enrolled. Patients with ST elevation myocardial infarction (STEMI) treated with urgent PCI accounted for 3.9% of cases; patients with STEMI treated with delayed PCI accounted for 20.5% of cases; patients with stable angina accounted for 16.5% of cases; and patients with non-ST elevation acute coronary syndrome (NSTE-ACS) accounted for 58.6% of cases. PRIMARY OUTCOMES: Death, major adverse cardiac and cerebrovascular events (MACCE: death/myocardial infarction/stroke), and target vessel revascularisation. RESULTS: Follow-up after a median of 29.8 months was obtained for 2533 patients (92.6%). The mortality rate during hospitalisation was highest in the urgent PCI group (p<0.001). During follow-up, although the incidences of death and MACCE were highest in the urgent PCI group, no significant differences were observed among the different groups. The incidences of cardiac death and myocardial infarction were significantly higher in the paclitaxel-eluting stent (PES) group than in the sirolimus-eluting stent (SES) group. Independent predictors of death during follow-up were age, left ventricular ejection function <40%, diabetes mellitus, prior coronary artery bypass graft and chronic total occlusion. CONCLUSIONS: PCI patients with STEMI had the worst hospital and long-term prognosis. The mortality rate after hospital increased markedly in patients with NSTE-ACS. SESs seem to be more effective than PESs. PMID- 25113555 TI - Effects of the First Line Diabetes Care (FiLDCare) self-management education and support project on knowledge, attitudes, perceptions, self-management practices and glycaemic control: a quasi-experimental study conducted in the Northern Philippines. AB - OBJECTIVES: To investigate the effects of implementing a context-adapted diabetes self-management education and support (DSME/S) project based on chronic care models in the Philippines, on knowledge, attitudes, self-management practices, adiposity/obesity and glycaemia of people with diabetes. DESIGN: Prospective quasi-experimental before-after study. PARTICIPANTS: 203 people with type 2 diabetes mellitus from two local government units in the Northern Philippines fulfilling set criteria. OUTCOME MEASURES: Context-adapted DSME/S was given to a cohort of people with diabetes by trained pre-existing local government healthcare personnel. Changes in knowledge, attitudes and self-management practices, body mass index, waist circumference, waist-hip ratio (WHR) and glycosylated haemoglobin (HbA1c) were measured 1 year after full project implementation. Non-parametric and parametric descriptive and inferential statistics including logistic regression analysis were done. RESULTS: Complete data were collected from 164 participants. Improvements in glycaemia, waist circumference, WHR, knowledge, some attitudes, adherence to medications and exercise, and an increase in fear of diabetes were significant. Reductions in HbA1c, regardless of level of control, were noted in 60.4%. Significant increase in knowledge (p<0.001), positive attitude (p=0.013), perceived ability to control blood glucose (p=0.004) and adherence to medications (p=0.001) were noted among those whose glycaemia improved. Significant differences between the subgroups whose HbA1c improved and those whose HbA1c deteriorated include male gender (p=0.042), shorter duration of diabetes (p=0.001) and increased perceived ability to control blood glucose (p=0.042). Significant correlates to improved glycaemia were male gender (OR=2.655; p=0.034), duration of diabetes >10 years (OR=0.214; p=0.003) and fear of diabetes (OR=0.490; p=0.048). CONCLUSIONS: Context-adapted DSME/S introduced in resource-constrained settings and making use of established human resources for health may improve knowledge, attitudes, self-management practices and glycaemia of recipients. Further investigations on addressing fear of diabetes and tailoring DSME/S to females with diabetes and those who have had diabetes for a longer period of time may help improve glycaemia. PMID- 25113556 TI - Assessing the feasibility of a randomised, double-blinded, placebo-controlled trial to investigate the role of intraperitoneal ropivacaine in gastric bypass surgery: a protocol. AB - INTRODUCTION: Postoperative pain control remains a major challenge for surgical procedures, including laparoscopic gastric bypass. Pain management is particularly relevant in obese patients who experience a higher number of cardiovascular and pulmonary events. Effective pain management may reduce their risk of serious postoperative complication, such as deep vein thrombosis and pulmonary emboli. The objective of this study is to evaluate the efficacy of intraperitoneal local anaesthetic, ropivacaine, to reduce postoperative pain in patients undergoing laparoscopic Roux-en-Y gastric bypass. METHODS AND ANALYSIS: A randomised controlled trial will be conducted to compare intraperitoneal ropivacaine (intervention) versus normal saline (placebo) in 120 adult patients undergoing bariatric bypass surgery. Ropivacaine will be infused over the oesophageal hiatus and throughout the abdomen. Patients in the control arm will undergo the same treatment with normal saline. The primary end point will be postoperative pain at 1, 2 and 4 h postoperatively. Pain measurements will then occur every 4 h for 24 h and every 8 h until discharge. Secondary end points will include opioid use, peak expiratory flow, 6 min walk distance and quality of life assessed in the immediate postoperative period. Intention-to-treat analysis will be used and repeated measures will be analysed using mixed modelling approach. Post-hoc pairwise comparison of the treatment groups at different time points will be carried out using multiple comparisons with adjustment to the type 1 error. Results of the study will inform the feasibility of recruitment and inform sample size of a larger definitive randomised trial to evaluate the effectiveness of intraperitoneal ropivacaine. ETHICS AND DISSEMINATION: This study has been approved by the Ottawa Health Science Network Research Ethics Board and Health Canada in April 2014. The findings of the study will be disseminated through national and international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov NCT02154763. PMID- 25113557 TI - Pneumococcal colonisation density: a new marker for disease severity in HIV infected adults with pneumonia. AB - OBJECTIVE: A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome. METHODS: Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci. RESULTS: There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01). CONCLUSIONS: In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults. PMID- 25113558 TI - PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation. AB - Neuroinflammation and endoplasmic reticulum (ER) stress are associated with many neurological diseases. Here, we have examined the interaction between ER stress and JAK/STAT-dependent inflammation in glial cells. We show that ER stress is present in the central nervous system (CNS) concomitant with inflammation and astrogliosis in the multiple sclerosis (MS) mouse model of experimental autoimmune encephalomyelitis (EAE). Astrocytes do not easily succumb to ER stress but rather activate an inflammatory program involving activation of STAT3 in a JAK1-dependent fashion. ER stress-induced activation of the JAK1/STAT3 axis leads to expression of interleukin 6 (IL-6) and several chemokines. Moreover, the activation of STAT3 signaling is dependent on PERK, a central component of the ER stress response, which we show is phosphorylated by JAK1. Disruption of PERK abrogates ER stress-induced activation of STAT3 and subsequent gene expression. Additionally, ER-stressed astrocytes, via paracrine signaling, can stimulate activation of microglia, leading to production of IL-6 and oncostatin M (OSM). These IL-6 cytokines can then synergize with ER stress in astrocytes to drive inflammation. Together, this work describes a new PERK/JAK1/STAT3 signaling pathway that elicits a feed-forward inflammatory loop involving astrocytes and microglia to drive neuroinflammation, which may be relevant in diseases such as MS. PMID- 25113561 TI - Plakophilin-2 promotes activation of epidermal growth factor receptor. AB - While growth factor-driven dimerization of receptor tyrosine kinases (RTKs) is a simple and intuitive mechanism of activating RTKs, K.-I. Arimoto et al. (Mol. Cell. Biol. 34:3843-3854, 2014, doi:10.1128/MCB.00758-14) describe a novel means of promoting the activity of RTKs. Namely, plakophilin-2 (PKP2) associates with the epidermal growth factor receptor (EGFR) and enhances its ligand-dependent and ligand-independent activity. This discovery suggests that antagonizing PKP2 may be a new therapeutic opportunity to combat tumors in which activation of EGFR contributes to pathogenesis. PMID- 25113559 TI - Regulation of the protocadherin Celsr3 gene and its role in globus pallidus development and connectivity. AB - The globus pallidus (GP) is a central component of basal ganglia whose malfunctions cause a variety of neuropsychiatric disorders as well as cognitive impairments in neurodegenerative diseases such as Parkinson's disease. Here we report that the protocadherin gene Celsr3 is regulated by the insulator CCCTC binding factor (CTCF) and the repressor neuron-restrictive silencer factor (NRSF, also known as REST) and is required for the development and connectivity of GP. Specifically, CTCF/cohesin and NRSF inhibit the expression of Celsr3 through specific binding to its promoter. In addition, we found that the Celsr3 promoter interacts with CTCF/cohesin-occupied neighboring promoters. In Celsr3 knockout mice, we found that the ventral GP is occupied by aberrant calbindin-positive cholinergic neurons ectopic from the nucleus basalis of Meynert. Furthermore, the guidepost cells for thalamocortical axonal development are missing in the caudal GP. Finally, axonal connections of GP with striatum, subthalamic nucleus, substantia nigra, and raphe are compromised. These data reveal the essential role of Celsr3 in GP development in the basal forebrain and shed light on the mechanisms of the axonal defects caused by the Celsr3 deletion. PMID- 25113560 TI - Plakophilin-2 promotes tumor development by enhancing ligand-dependent and independent epidermal growth factor receptor dimerization and activation. AB - Epidermal growth factor (EGF) receptor (EGFR) has been implicated in tumor development and invasion. Dimerization and autophosphorylation of EGFR are the critical events for EGFR activation. However, the regulation of EGF-dependent and EGF-independent dimerization and phosphorylation of EGFR has not been fully understood. Here, we report that cytoplasmic protein plakophilin-2 (PKP2) is a novel positive regulator of EGFR signaling. PKP2 specifically interacts with EGFR via its N-terminal head domain. Increased PKP2 expression enhances EGF-dependent and EGF-independent EGFR dimerization and phosphorylation. Moreover, PKP2 knockdown reduces EGFR phosphorylation and attenuates EGFR-mediated signal activation, resulting in a significant decrease in proliferation and migration of cancer cells and tumor development. Our results indicate that PKP2 is a novel activator of the EGFR signaling pathway and a potential new drug target for inhibiting tumor growth. PMID- 25113563 TI - Special issue of BJP on nanomedicine. PMID- 25113562 TI - Piwil2 inhibits keratin 8 degradation through promoting p38-induced phosphorylation to resist Fas-mediated apoptosis. AB - The piwi-like 2 (piwil2) gene is widely expressed in tumors and protects cells from apoptosis induced by a variety of stress stimuli. However, the role of Piwil2 in Fas-mediated apoptosis remains unknown. Here, we present evidence that Piwil2 inhibits Fas-mediated apoptosis. By a bacterial two-hybrid screening, we identify a new Piwil2-interacting partner, keratin 8 (K8), a major intermediate filament protein protecting the cell from Fas-mediated apoptosis. Our results show that Piwil2 binds to K8 and p38 through its PIWI domain and forms a Piwil2/K8/P38 triple protein-protein complex. Thus, Piwil2 increases the phosphorylation level of K8 Ser-73 and then inhibits ubiquitin-mediated degradation of K8. As a result, the knockdown of Piwil2 increases the Fas protein level at the membrane. In addition to our previous finding that Piwil2 inhibits the expression of p53 through the Src/STAT3 pathway, here we demonstrate that Piwil2 represses p53 phosphorylation through p38. Our present study indicates that Piwil2 plays a role in Fas-mediated apoptosis for the first time and also can affect p53 phosphorylation in tumor cells, revealing a novel mechanism of Piwil2 in apoptosis, and supports that Piwil2 plays an active role in tumorigenesis. PMID- 25113564 TI - Human fibrocytic myeloid-derived suppressor cells express IDO and promote tolerance via Treg-cell expansion. AB - By restraining T-cell activation and promoting Treg-cell expansion, myeloid derived suppressor cells (MDSCs) and tolerogenic DCs can control self-reactive and antigraft effector T cells in autoimmunity and transplantation. Their therapeutic use and characterization, however, is limited by their scarce availability in the peripheral blood of tumor-free donors. In the present study, we describe and characterize a novel population of human myeloid suppressor cells, named fibrocytic MDSC, which are differentiated from umbilical cord blood precursors by 4-day culture with FDA-approved cytokines (recombinant human-GM-CSF and recombinant human-G-CSF). This MDSC subset, characterized by the expression of MDSC-, DC-, and fibrocyte-associated markers, promotes Treg-cell expansion and induces normoglycemia in a xenogeneic mouse model of Type 1 diabetes. In order to exert their protolerogenic function, fibrocytic MDSCs require direct contact with activated T cells, which leads to the production and secretion of IDO. This new myeloid subset may have an important role in the in vitro and in vivo production of Treg cells for the treatment of autoimmune diseases, and in either the prevention or control of allograft rejection. PMID- 25113565 TI - Genistein attenuates choroidal neovascularization. AB - Genistein is a dietary-derived flavonoid abundantly present in soybeans and known to possess various biological effects including anti-inflammation and anti angiogenic activity. To investigate the effects of genistein on intraocular neovascularization, we used an animal model of laser-induced choroidal neovascularization (CNV). Male C57BL/6J mice were treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. CNV was induced by laser photocoagulation. The animals were fed a mixture diet containing 0.5% genistein or a control diet ad libitum for 7 days before laser photocoagulation and the treatment was continued until the end of the study. Seven days after laser injury, the size of CNV lesions was quantified. Retinal pigment epithelium (RPE)-choroid complex was also harvested 1 or 3 days after laser injury and the level of monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, and matrix metalloproteinase (MMP)-9 were measured by enzyme-linked immunosorbent assay. Expression levels of Ets-1 and F4/80 were examined by real-time PCR. A significant decrease in CNV size was observed in animals treated with genistein (15441.9+/-1511.8 MUm(2)) compared to control mice (21074.0+/-1940.7MUm(2), P<.05). Genistein significantly reduced the protein level of MCP-1, ICAM-1, and MMP-9 in the RPE-choroid complex (P<.05). In addition, genistein suppressed the expression levels of Ets-1 and F4/80 (P<.05). The current data indicate the anti-angiogenic property of genistein during CNV formation. PMID- 25113566 TI - What can genes tell us about the relationship between education and health? AB - We use genome wide data from respondents of the Health and Retirement Study (HRS) to evaluate the possibility that common genetic influences are associated with education and three health outcomes: depression, self-rated health, and body mass index. We use a total of 1.7 million single nucleotide polymorphisms obtained from the Illumina HumanOmni2.5-4v1 chip from 4233 non-Hispanic white respondents to characterize genetic similarities among unrelated persons in the HRS. We then used the Genome Wide Complex Trait Analysis (GCTA) toolkit, to estimate univariate and bivariate heritability. We provide evidence that education (h(2) = 0.33), BMI (h(2) = 0.43), depression (h(2) = 0.19), and self-rated health (h(2) = 0.18) are all moderately heritable phenotypes. We also provide evidence that some of the correlation between depression and education as well as self-rated health and education is due to common genetic factors associated with one or both traits. We find no evidence that the correlation between education and BMI is influenced by common genetic factors. PMID- 25113568 TI - Adding insult to injury: The development of psychosocial stress in Ontario wind turbine communities. AB - Though historically dismissed as not-in-my-backyard (NIMBY) attitudes, reports of psychosocial stress linked to wind energy developments have emerged in Ontario, Canada. While the debate and rhetoric intensify concerning whether wind turbines 'actually' cause 'health' effects, less sincere attention has been given to the lived experience and mental well-being of those near turbines. Drawing on theories of environmental stress, this grounded theory, mixed-method (n = 26 interviews; n = 152 questionnaires) study of two communities in 2011 and 2012 traces how and why some wind turbine community residents suffer substantial changes to quality of life, develop negative perceptions of 'the other' and in some cases, experience intra-community conflict. Policy-related forces, along with existing community relationships may help explain much of these differences between communities. We suggest a move beyond debating simply whether or not 'annoyance' represents a 'health impact' and instead focus on ways to minimize and attenuate these feelings of threat (risk) and stress at the community level. PMID- 25113567 TI - When does education matter? The protective effect of education for cohorts graduating in bad times. AB - Using Eurobarometer data, we document large variation across European countries in education gradients in income, self-reported health, life satisfaction, obesity, smoking and drinking. While this variation has been documented previously, the reasons why the effect of education on income, health and health behaviors varies is not well understood. We build on previous literature documenting that cohorts graduating in bad times have lower wages and poorer health for many years after graduation, compared to those graduating in good times. We investigate whether more educated individuals suffer smaller income and health losses as a result of poor labor market conditions upon labor market entry. We confirm that a higher unemployment rate at graduation is associated with lower income, lower life satisfaction, greater obesity, more smoking and drinking later in life. Further, education plays a protective role for these outcomes, especially when unemployment rates are high: the losses associated with poor labor market outcomes are substantially lower for more educated individuals. Variation in unemployment rates upon graduation can potentially explain a large fraction of the variance in gradients across different countries. PMID- 25113570 TI - Recreational participation and the development of social competence in preschool aged children with disabilities: a cross-sectional study. AB - PURPOSE: To explore the association between participation and social competence for preschool aged children with and without disabilities. METHODS: The sample was drawn from the Longitudinal Study of Australian Children (n = 4983) which included children aged 4-5 years reported to have hearing problems (n = 164), vision problems (n = 146) and other physical disabilities (n = 114). Chi-square, correlation and logistic regression analyses were used to describe the participation and social competence of children with and without these conditions, as well as examine the association between these constructs. RESULTS: Children with disabilities had similar levels of participation but lower social competence than children without these disabilities. Further analyses revealed a small negative correlation between the two variables (ranging from -0.120 to 0.300 for the three groups) and that children who have low participation are more likely to have abnormal levels of social competence than children with higher participation. CONCLUSIONS: The association between participation and social competence may not be as strong for this age group as anticipated in the literature, additional factors may be influential. Examination of the social competence scores identified two factors which may assist in explaining the variance in scores: (1) the experience of disability and (2) the quality of interactions. IMPLICATIONS FOR REHABILITATION: Children with disabilities who participate in similar activities to their typically developing peers may not necessarily develop commensurate levels of social competence. As well as focusing on increasing the participation of children in activities other factors that may have a stronger influence on social competence should be considered, such as supporting (1) the social experience of disability and (2) the quality of interactions that children with disabilities experience. PMID- 25113571 TI - A day in the life of older people in a rehabilitation setting: an observational study. AB - PURPOSE: Nurses' contribution during inpatient rehabilitation is well documented. However, despite being the largest professional group in this setting, the specialty of rehabilitation nursing is poorly recognised. This article reports on the first of a four-phase study that aimed to clarify and develop the nursing contribution to inpatient rehabilitation for older persons. The aim of this study was to identify activity patterns and time use during daytime and evenings of older adult patients undergoing inpatient rehabilitation. METHODS: Direct observation using behavioural modelling was undertaken of a convenience sample of 37 older people undergoing inpatient rehabilitation in a specialist unit of a large tertiary hospital in New Zealand. The primary outcome was the observation of meaningful activity. Binomial logistic regression was used to study the association between relevant variables. FINDINGS: Meaningful activity was most likely to involve walking without assistance and to occur 08:00 to 14:00 h and 16:00 to 21:00 h during weekdays. Patients were more likely to receive treatment during the weekend. Irrespective of time, registered nurses were the health professionals most often present with patients. CONCLUSIONS: There is likely to be unrealised opportunities for registered nurses to support improved rehabilitation outcomes. Registered nurses' involvement in rehabilitation needs to be actively optimised. IMPLICATIONS FOR REHABILITATION: Nurses' engagement with older adults in rehabilitation settings is likely to be substantial, placing them as key members of the rehabilitation team. Nurses make a pivotal contribution to inpatient rehabilitation based on specialised knowledge and skills but this contribution is not well understood. Opportunities are likely, at times when allied health professionals are less often present, e.g. evenings and weekends, for registered nurses to more intentionally overlap rehabilitation activities with other care requirements. PMID- 25113572 TI - Supporting the Loewenstein occupational therapy cognitive assessment using distributed user interfaces. AB - PURPOSE: Improve the quantity and quality of information obtained from traditional Loewenstein Occupational Therapy Cognitive Assessment Battery systems to monitor the evolution of patients' rehabilitation process as well as to compare different rehabilitation therapies. METHODS: The system replaces traditional artefacts with virtual versions of them to take advantage of cutting edge interaction technology. The system is defined as a Distributed User Interface (DUI) supported by a display ecosystem, including mobile devices as well as multi-touch surfaces. Due to the heterogeneity of the devices involved in the system, the software technology is based on a client-server architecture using the Web as the software platform. RESULTS: The system provides therapists with information that is not available (or it is very difficult to gather) using traditional technologies (i.e. response time measurements, object tracking, information storage and retrieval facilities, etc.). CONCLUSIONS: The use of DUIs allows therapists to gather information that is unavailable using traditional assessment methods as well as adapt the system to patients' profile to increase the range of patients that are able to take this assessment. Implications for Rehabilitation Using a Distributed User Interface environment to carry out LOTCAs improves the quality of the information gathered during the rehabilitation assessment. This system captures physical data regarding patient's interaction during the assessment to improve the rehabilitation process analysis. Allows professionals to adapt the assessment procedure to create different versions according to patients' profile. Improves the availability of patients' profile information to therapists to adapt the assessment procedure. PMID- 25113573 TI - A stair-climbing test for measuring mechanical efficiency of ambulation in adults with chronic stroke. AB - PURPOSE: Mechanical efficiency can assess motor performance in individuals with physical disabilities. The purpose was to determine the utility of predicting it from heart rate (HR) during a self-paced stair-climbing test in adults with chronic hemiparesis after stroke and to determine the minimal detectable change of net mechanical efficiency (MEnet) measured by this exercise. METHODS: First, 15 subjects with chronic hemiparesis participated in a validation study (A) and then 28 took part in a repeatability study (B). In study A the MEnet was calculated from external work and oxygen uptake above rest (dVO2), as directly measured and as predicted from body weight and increase in heart rate (dHR). In study B, predicted dVO2 was used to obtain MEnet for duplicate stair-climbing tests (T1, T2) with >30 min rest between. RESULTS: Measured MEnet was closely related to predicted MEnet (r = 0.97, p < 0.001). In study B predicted MEnet for T2 and T1 were closely related (r = 0.91, ICC = 0.90). CONCLUSION: With a minimal detectable change of 0.6% (0.053 of average MEnet score of 10.4%), MEnet values from the stair-climbing test seem sufficiently meaningful to estimate ambulatory ability and its changes with interventions or walking aids in adults with hemiparesis. IMPLICATIONS FOR REHABILITATION: Ambulatory ability can be estimated from mechanical efficiency, obtained from a 5-min stair-climbing test utilizing a 4-step stair, to measure external work, and the change in heart rate above rest to estimate the metabolic cost of the task. A change of > 0.6% in mechanical efficiency by this stair-climbing test indicates a significant change in ambulatory ability of persons with hemiparesis. PMID- 25113574 TI - Serratus anterior muscle pedicle as the recipient site in DIEP flap transfer for breast reconstruction: why not the first choice? PMID- 25113575 TI - A structural and spectroscopic investigation of octahedral platinum bis(dithiolene)phosphine complexes: platinum dithiolene internal redox chemistry induced by phosphine association. AB - The complexes [Pt(mdt)2] (4; mdt = methyldithiolene, [Me2C2S2](n-)), [Pt(adt)2] (5; adt = p-anisyldithiolene, [(MeO-p-C6H4)2C2S2](n-)), and [Pd(adt)2] (10) have been prepared in yields of >=90% via transmetalation reactions with the corresponding [R2Sn(S2C2R'2)] complexes (R = (n)Bu, R' = Me; R = Me, R' = -C6H4-p OMe, 3). Intraligand C-S and C-Cchelate bond lengths (~1.71 and ~1.40 A, respectively) obtained by X-ray crystallography show these compounds to be comprised of radical monoanions mdt(*-) and adt(*-). The six-coordinate octahedral adducts [Pt(adt)2(dppe)] [6; dppe = 1,2-bis(diphenylphosphino)ethane], trans-[Pt(adt)2(PMe3)2] (8), and trans-[Pt(mdt)2(PMe3)2] (9) have also been prepared, and crystal structures reveal dithiolene ligands that are fully reduced ene-1,2-dithiolates (C-S and C-C(chelate) = ~1.77 and 1.35 A, respectively). Reduction of the dithiolene ligand thus occurs to accommodate the +IV oxidation state typical of octahedral six-coordinate platinum. The cyclic voltammogram of 5 shows two fully reversible reductions at -0.11 and -0.84 V in CH2Cl2 (vs Ag/AgCl), attributed to successive (adt(*-) + e(-) -> adt(2-)) processes, and a reversible oxidation at +1.01 V. The cyclic voltammogram of 9 shows two reversible oxidations at +0.38 and +0.86 V, which are assigned as successive (adt(2-) -> adt(*-) + e(-)) oxidations. Consistent with their formulation as having fully reduced dithiolene ligands, the UV-vis spectra for 6, 8, and 9 show no low-energy absorptions below 700 nm, and the S K-edge XAS spectra of 6 and 8 show dithiolene sulfur that is reduced relative to that in 5. The introduction of PMe3 to 10 did not produce the palladium analogue of 8 but rather [Pd(adt)(PMe3)2] (11). The reaction of [PdCl2(PPh3)2] with Li2(mdt) produced a mixture of [Pd(mdt)(PPh3)2] (12, 20%) and [(Ph3P)Pd(MU-1,2-mdt-S,S':S)2Pd(PPh3)] (13, 28%), with the latter having C2 symmetry with a Pd2S2 core structure folded along the S...S axis. PMID- 25113576 TI - Familias 3 - Extensions and new functionality. AB - In relationship testing the aim is to determine the most probable pedigree structure given genetic marker data for a set of persons. Disaster Victim Identification (DVI) based on DNA data from presumed relatives of the missing persons can be considered to be a collection of relationship problems. Forensic calculations in investigative mode address questions like "How many markers and reference persons are needed?" Such questions can be answered by simulations. Mutations, deviations from Hardy-Weinberg Equilibrium (or more generally, accounting for population substructure) and silent alleles cannot be ignored when evaluating forensic evidence in case work. With the advent of new markers, so called microvariants have become more common. Previous mutation models are no longer appropriate and a new model is proposed. This paper describes methods designed to deal with DVI problems and a new simulation model to study distribution of likelihoods. There are softwares available, addressing similar problems. However, for some problems including DVI, we are not aware of freely available validated software. The Familias software has long been widely used by forensic laboratories worldwide to compute likelihoods in relationship scenarios, though previous versions have lacked desired functionality, such as the above mentioned. The extensions as well as some other novel features have been implemented in the new version, freely available at www.familias.no. The implementation and validation are briefly mentioned leaving complete details to Supplementary sections. PMID- 25113577 TI - Choosing supplementary markers in forensic casework. AB - The vast majority of human familial identifications based on DNA end up with a well founded conclusion, normally using a standard set of genetic short tandem repeat (STR) loci. There are, however, a proportion of cases that show ambiguous results. For such occasions a number of different supplementary markers could be typed in order to gain further information. There are numerous markers available for such supplementary DNA typing, including STRs, deletion and insertion polymorphisms (DIPs), and single nucleotide polymorphisms (SNPs). The purpose of this work was to describe a precise method for decision making, aiming to aid the comparison of different sets of markers for different case scenarios in order to find the most efficient set for routine casework. Comparisons are based on a particular function relating the expected additional value of information from new data to the amount of information already obtained from initial data. The function can be computed approximately by approximating likelihood-based error rates using simulation. In this paper we focused on paternity investigations, more specifically the use of supplementary markers in cases where a smaller number of genetic inconsistencies make the matter inconclusive. We applied the method to a comparison of three different kits: Investigator HDplex (STRs), Investigator DIPplex (DIPs), and the SNPforID-plex (SNPs) to study their efficiencies in gaining information in different case scenarios involving various alternative relationships between the tested man and the tested child. We show that the Investigator HDplex was the most efficient set of supplementary markers for the standard paternity case. However, for paternity cases with a close relative being the alternative father, the Investigator HDplex and the SNPforID plex showed similar patterns in their ability to deliver a well-founded conclusion. The Investigator DIPplex was the least efficient set. PMID- 25113580 TI - Anterior segment optical coherence tomography in autosomal recessive cornea plana. PMID- 25113582 TI - Oxygenation by ruthenium monosubstituted polyoxotungstates in aqueous solution: experimental and computational dissection of a Ru(III)-Ru(V) catalytic cycle. AB - Molecular polyoxometalates with one embedded ruthenium center, with general formula [Ru(II/III)(DMSO)XW11O39](n-) (X = P, Si; n = 4-6), are readily synthesized in gram scale under microwave irradiation by a flash hydrothermal protocol. These nanodimensional and polyanionic complexes enable aerobic oxygenation in water. Catalytic oxygen transfer to dimethylsulfoxide (DMSO) yielding the corresponding sulfone (DMSO2 ) has been investigated with a combined kinetic, spectroscopic and computational approach addressing: (i ) the Ru(III) catalyst resting state; (ii ) the bimolecular event dictating its transformation in the rate-determining step; (iii ) its aerobic evolution to a high-valent ruthenium oxene species; (iv ) the terminal fate to diamagnetic dimers. This pathway is reminiscent of natural heme systems and of bioinspired artificial porphyrins. The in silico characterization of a key bis-Ru(IV)-MU-peroxo-POM dimeric intermediate has been accessed by density functional theory. This observation indicates a new landmark for tracing POM-based manifolds for multiredox oxygen reduction/activation, where metal-centered oxygenated species play a pivotal role. PMID- 25113581 TI - Fluoride inhibition of Sporosarcina pasteurii urease: structure and thermodynamics. AB - Urease is a nickel-dependent enzyme and a virulence factor for ureolytic bacterial human pathogens, but it is also necessary to convert urea, the most worldwide used fertilizer, into forms of nitrogen that can be taken up by crop plants. A strategy to control the activity of urease for medical and agricultural applications is to use enzyme inhibitors. Fluoride is a known urease inhibitor, but the structural basis of its mode of inhibition is still undetermined. Here, kinetic studies on the fluoride-induced inhibition of urease from Sporosarcina pasteurii, a widespread and highly ureolytic soil bacterium, were performed using isothermal titration calorimetry and revealed a mixed competitive and uncompetitive mechanism. The pH dependence of the inhibition constants, investigated in the 6.5-8.0 range, reveals a predominant uncompetitive mechanism that increases by increasing the pH, and a lesser competitive inhibition that increases by lowering the pH. Ten crystal structures of the enzyme were independently determined using five crystals of the native form and five crystals of the protein crystallized in the presence of fluoride. The analysis of these structures revealed the presence of two fluoride anions coordinated to the Ni(II) ions in the active site, in terminal and bridging positions. The present study consistently supports an interaction of fluoride with the nickel centers in the urease active site in which one fluoride competitively binds to the Ni(II) ion proposed to coordinate urea in the initial step of the catalytic mechanism, while another fluoride uncompetitively substitutes the Ni(II)-bridging hydroxide, blocking its nucleophilic attack on urea. PMID- 25113584 TI - Concise review: understanding clonal dynamics in homeostasis and injury through multicolor lineage tracing. AB - Lineage tracing is an essential tool to study stem cell fate. Although traditional lineage tracing techniques have considerably advanced our understanding of stem cell behavior, they pose significant limitations for identification and longitudinal tracking of the progeny of individual stem cells, to compare their behaviors. This is of importance given the well-established heterogeneity among stem cells both in terms of potentialities and proliferative capacities. The recent development of multicolor genetic reporters addressable to specific cell populations largely overcomes these issues. These new "rainbow" technologies provide increased resolution in clonal identification and offer the possibility to study the relative distribution, contacts, tiled arrangement, and competitive interactions among cells or groups of cells of the same type. PMID- 25113583 TI - Effect of genetic and pharmacological blockade of GABA receptors on the 5-HT2C receptor function during stress. AB - Serotonin (5-HT)2C receptors play a role in psychoaffective disorders and often contribute to the antidepressant and anxiolytic effects of psychotropic drugs. During stress, activation of these receptors exerts a negative feedback on 5-HT release, probably by increasing the activity of GABAergic interneurons. However, to date, the GABA receptor types that mediate the 5-HT2C receptor-induced feedback inhibition are still unknown. To address this question, we assessed the inhibition of 5-HT turnover by a 5-HT2C receptor agonist (RO 60-0175) at the hippocampal level and under conditions of stress, after pharmacological or genetic inactivation of either GABA-A or GABA-B receptors in mice. Neither the GABA-B receptor antagonist phaclofen nor the specific genetic ablation of either GABA-B1a or GABA-B1b subunits altered the inhibitory effect of RO 60-0175, although 5-HT turnover was markedly decreased in GABA-B1a knock-out mice in both basal and stress conditions. In contrast, the 5-HT2C receptor-mediated inhibition of 5-HT turnover was reduced by the GABA-A receptor antagonist bicuculline. However, a significant effect of 5-HT2C receptor activation persisted in mutant mice deficient in the alpha3 subunit of GABA-A receptors. It can be inferred that non-alpha3 subunit-containing GABA-A receptors, but not GABA-B receptors, mediate the 5-HT2C -induced inhibition of stress-induced increase in hippocampal 5-HT turnover in mice. PMID- 25113586 TI - Spatio-temporal variability of bovine tuberculosis eradication in Spain (2006 2011). AB - In this study we analyzed the space-time variation of the risk of bovine tuberculosis (bTB) in cattle between 2006 and 2011. The results indicated that at country level, there were no significant temporal changes between years, but, at county level bTB evolution was more heterogeneous. In some counties, between some years, the prevalence and the incidence of the disease was higher as compared to the global rate in the rest of the counties of Spain. The analysis of potential risk factors indicated that both, a large number of movements from counties with high incidence (>1%), and presence of bullfighting cattle herds increased bTB risk. Red deer abundance, number of goats and number of mixed cattle-goat farms were not significantly associated with the prevalence/incidence of bTB. PMID- 25113587 TI - The choice of spatial scales and spatial smoothness priors for various spatial patterns. AB - Given the drawbacks for using geo-political areas in mapping outcomes unrelated to geo-politics, a compromise is to aggregate and analyse data at the grid level. This has the advantage of allowing spatial smoothing and modelling at a biologically or physically relevant scale. This article addresses two consequent issues: the choice of the spatial smoothness prior and the scale of the grid. Firstly, we describe several spatial smoothness priors applicable for grid data and discuss the contexts in which these priors can be employed based on different aims. Two such aims are considered, i.e., to identify regions with clustering and to model spatial dependence in the data. Secondly, the choice of the grid size is shown to depend largely on the spatial patterns. We present a guide on the selection of spatial scales and smoothness priors for various point patterns based on the two aims for spatial smoothing. PMID- 25113588 TI - GEOMED 2013--from spatial analysis to public health practice. PMID- 25113585 TI - Low adherence to secondary prophylaxis among clients diagnosed with rheumatic fever, Jamaica. AB - OBJECTIVES: To determine the level of adherence and possible barriers to secondary prophylaxis among clients with rheumatic fever in Kingston, Jamaica. METHODS: Cross-sectional survey of 39 clients diagnosed with rheumatic fever, receiving penicillin prophylaxis for more than a year using a 22-item self administered questionnaire on adherence to secondary prophylaxis and knowledge of rheumatic fever. The patients' records were reviewed to determine the number of prophylaxis injections the patients received for the year 2010. RESULTS: The majority of participants (74%) were females and 51% were adults. Only 48.7% had a high level of adherence. The majority (72%) had low knowledge levels regarding their illness, while only 5% had a high knowledge level score. Most clients (70%) strongly agreed that nurses and doctors encouraged them to take their prophylaxis. However, over 60% reported that they travelled long distances and or waited long periods to get their injections. One-third reported that they missed appointments because of fear of injections and having to take time off from work or school. DISCUSSION: Clients attending the health centers studied had limited knowledge about rheumatic fever. Barriers to adherence included fear of the injections, long commutes, and long waiting periods at the facilities studied. PMID- 25113589 TI - A spatio-temporal model for estimating the long-term effects of air pollution on respiratory hospital admissions in Greater London. AB - It has long been known that air pollution is harmful to human health, as many epidemiological studies have been conducted into its effects. Collectively, these studies have investigated both the acute and chronic effects of pollution, with the latter typically based on individual level cohort designs that can be expensive to implement. As a result of the increasing availability of small-area statistics, ecological spatio-temporal study designs are also being used, with which a key statistical problem is allowing for residual spatio-temporal autocorrelation that remains after the covariate effects have been removed. We present a new model for estimating the effects of air pollution on human health, which allows for residual spatio-temporal autocorrelation, and a study into the long-term effects of air pollution on human health in Greater London, England. The individual and joint effects of different pollutants are explored, via the use of single pollutant models and multiple pollutant indices. PMID- 25113590 TI - Bayesian tracking of emerging epidemics using ensemble optimal statistical interpolation. AB - We present a preliminary test of the Ensemble Optimal Statistical Interpolation (EnOSI) method for the statistical tracking of an emerging epidemic, with a comparison to its popular relative for Bayesian data assimilation, the Ensemble Kalman Filter (EnKF). The spatial data for this test was generated by a spatial susceptible-infectious-removed (S-I-R) epidemic model of an airborne infectious disease. Both tracking methods in this test employed Poisson rather than Gaussian noise, so as to handle epidemic data more accurately. The EnOSI and EnKF tracking methods worked well on the main body of the simulated spatial epidemic, but the EnOSI was able to detect and track a distant secondary focus of infection that the EnKF missed entirely. PMID- 25113591 TI - Real geographies and virtual landscapes: exploring the influence on place and space on mortality Lexis surfaces using shaded contour maps. AB - This paper describes how shaded contour plots, applied to mortality data from the Human Mortality Database, can be used to compare between nations, and start to tease out some of the ways that place and space matters. A number of shaded contour plots are presented, in order to describe the age, period and cohort effects which are apparent within them. They show variations between different subpopulations within the same nation, over time, and between nations. In illustrating these intra- and international variations in the patterns, we hope to encourage the development of hypotheses about the influence of such factors on mortality rates. We conclude with a brief discussion about how such hypotheses might be developed into statistical models, allowing for more rigourous testing of hypotheses and projection across time, place and space. PMID- 25113592 TI - Using geographical information systems and cartograms as a health service quality improvement tool. AB - INTRODUCTION: Disease prevalence can be spatially analysed to provide support for service implementation and health care planning, these analyses often display geographic variation. A key challenge is to communicate these results to decision makers, with variable levels of Geographic Information Systems (GIS) knowledge, in a way that represents the data and allows for comprehension. The present research describes the combination of established GIS methods and software tools to produce a novel technique of visualising disease admissions and to help prevent misinterpretation of data and less optimal decision making. The aim of this paper is to provide a tool that supports the ability of decision makers and service teams within health care settings to develop services more efficiently and better cater to the population; this tool has the advantage of information on the position of populations, the size of populations and the severity of disease. METHODS: A standard choropleth of the study region, London, is used to visualise total emergency admission values for Chronic Obstructive Pulmonary Disease and bronchiectasis using ESRI's ArcGIS software. Population estimates of the Lower Super Output Areas (LSOAs) are then used with the ScapeToad cartogram software tool, with the aim of visualising geography at uniform population density. An interpolation surface, in this case ArcGIS' spline tool, allows the creation of a smooth surface over the LSOA centroids for admission values on both standard and cartogram geographies. The final product of this research is the novel Cartogram Interpolation Surface (CartIS). RESULTS: The method provides a series of outputs culminating in the CartIS, applying an interpolation surface to a uniform population density. The cartogram effectively equalises the population density to remove visual bias from areas with a smaller population, while maintaining contiguous borders. CartIS decreases the number of extreme positive values not present in the underlying data as can be found in interpolation surfaces. DISCUSSION: This methodology provides a technique for combining simple GIS tools to create a novel output, CartIS, in a health service context with the key aim of improving visualisation communication techniques which highlight variation in small scale geographies across large regions. CartIS more faithfully represents the data than interpolation, and visually highlights areas of extreme value more than cartograms, when either is used in isolation. PMID- 25113593 TI - Assessment of land use factors associated with dengue cases in Malaysia using Boosted Regression Trees. AB - The transmission of dengue disease is influenced by complex interactions among vector, host and virus. Land use such as water bodies or certain agricultural practices have been identified as likely risk factors for dengue because of the provision of suitable habitats for the vector. Many studies have focused on the land use factors of dengue vector abundance in small areas but have not yet studied the relationship between land use factors and dengue cases for large regions. This study aims to clarify if land use factors other than human settlements, e.g. different types of agricultural land use, water bodies and forest are associated with reported dengue cases from 2008 to 2010 in the state of Selangor, Malaysia. From the correlative relationship, we aim to generate a prediction risk map. We used Boosted Regression Trees (BRT) to account for nonlinearities and interactions between the factors with high predictive accuracies. Our model with a cross-validated performance score (Area Under the Receiver Operator Characteristic Curve, ROC AUC) of 0.81 showed that the most important land use factors are human settlements (model importance of 39.2%), followed by water bodies (16.1%), mixed horticulture (8.7%), open land (7.5%) and neglected grassland (6.7%). A risk map after 100 model runs with a cross validated ROC AUC mean of 0.81 (+/-0.001 s.d.) is presented. Our findings may be an important asset for improving surveillance and control interventions for dengue. PMID- 25113595 TI - Terrestrial and freshwater Tardigrada of the Americas. AB - This paper provides a comprehensive list of the freshwater and terrestrial tardigrade fauna reported from the Americas (North America, South America, Central America and the West Indies), their distribution in the Americas, and the substrates from which they have been reported. Data were obtained from 316 published references. Authors' identifications were accepted at face value unless subsequently amended. Taxa were assigned to sub-national units (states, provinces, etc.). Many areas, in particular large portions of Central America and the West Indies, have no reported tardigrade fauna. The presence of 54 genera and 380 species has been reported for the Americas; 245 species have been collected in the Nearctic ecozone and 251 in the Neotropical ecozone. Among the tardigrade species found in the Americas, 52 are currently considered cosmopolitan, while 153 species have known distributions restricted to the Americas. Based on recent taxonomic revision of the genus Milnesium, the vast majority of records of M. tardigradum in the Americas should now be reassigned to Milnesium tardigradum sensu lato, either because the provided description differs from M. tardigradum sensu stricto or because insufficient description is provided to make a determination; the remainder should be considered Milnesium cf. tardigradum. Most terrestrial tardigrade sampling in the Americas has focused on cryptogams (mosses, lichens and liverworts); 90% of the species have been collected in such substrates. The proportion of species collected in other habitats is lower: 14% in leaf litter, 20% in soil, and 24% in aquatic samples (in other terrestrial substrates the proportion never exceeds 5%). Most freshwater tardigrades have been collected from aquatic vegetation and sediment. For nine species in the Americas no substrates have been reported. PMID- 25113594 TI - Assessing the impact of selective migration and care homes on geographical inequalities in health--a total population cohort study in Sheffield. AB - Selective migration and moves to care homes may potentially contribute to observed socioeconomic gradients in mortality across cities and regions. Sheffield has striking socioeconomic gradients in area-level mortality across the city. We examined for evidence of selective migration and assessed the contribution of migration to observed mortality gradients. We used a total population cohort (539737 in 2001), linked mortality data (2001-2010) and linked data from a health survey carried out in 2000 (66% response rate yielding 10185 responses). We used lower super-output areas and electoral wards as the spatial units of analysis. We found clear evidence of selective migration. In the 25-44 age band, relative risks of mortality were 1.71 (95% CI 1.37-2.12) in migrants from low to high deprivation areas compared with people remaining in low deprivation areas, and 0.53 (0.42-0.65) in migrants from high to low deprivation areas compared with people remaining in high deprivation areas. Relative risks shrank towards unity with increasing age. Characteristics of migrants and non migrants (illness prevalence, indicators of socioeconomic status, smoking prevalence) ascertained before migration were largely consistent with the relative risks for mortality and indicated that people carried their risks with them. There was also a clear care homes effect, with higher mortality in electoral wards with higher care home bed provision rates. Overall, however, adjustment for selective migration, which included moves to care homes, made little difference to gradients in inequality across the city. Our results suggest that selective migration, including moves to care homes, do not explain existing socioeconomic gradients in area level mortality across Sheffield. PMID- 25113596 TI - A taxonomic review of the genus Megalostomis Chevrolat (Coleoptera, Cryptocephalinae, Chrysomelidae). AB - A taxonomic revision of the genus Megalostomis Chevrolat, 1836 (Coleoptera: Chrysomelidae: Cryptocephalinae: Clytrini: Megalostomina) is provided, including new data on geographic ranges. Two new species and 34 new synonymies are proposed within the genus Megalostomis, leaving 42 valid species in the genus. A checklist of the species of Megalostomis is provided, with information on host plants, ant associations, and natural enemies. The study includes a key to all species, diagnoses, descriptions, habitat, photographs, and distribution maps. This comparative study of the external and internal adult morphology includes the male and female genitalia. Nomenclatural acts proposed in this revision are as follow: Change of status: M. dynamica stat. rev. (=M. flavipennis dynamica Monros, 1952). New synonymy: M. anachoreta Lacordaire, 1848 (=M. gratiosa Lacordaire, 1848, syn. nov., M. amazona Jacoby, 1876, syn. nov., M. generosa Baly, 1877a, syn. nov., M. balyi Monros, 1951a, syn. nov., M. mariae Monros 1951a, new status syn., M. hespenheidi Moldenke, 1981, syn. nov.); M. basilaris Jacoby, 1880 (= M. runa Monros, 1952, syn. nov.); M. cornuta Lacordaire, 1848 (=M. cornuta var. divisa Guerin, 1949, syn. nov.); M. dimidiata dimidiata (Lacordaire, 1848) (= M. tomentosa tomentosa Jacoby, 1880, syn. nov., M. punctatissima (Jacoby, 1888), syn. nov., M. tomentosa orientalis Moldenke, 1970, syn. nov., M. tomentosa sinaloensis Moldenke, 1970, syn. nov., M. tomentosa guatemalensis Achard, 1926 (2nd specimen only), syn. nov., M. dimidiata nayaritensis Moldenke, 1970, syn. nov., M. dimidiata sonorensis Moldenke, 1970, syn. nov.); M. flavocincta Lacordaire, 1848 (=M. flavomaculata Lacordaire, 1848, syn. nov.); M. fulvipes fulvipes Jacoby, 1888 (=M. fulvipes yucatanensis Moldenke, 1970, syn. nov.); M. gazella Lacordaire 1848 (=M. bicingulata, Lacordaire, 1848, syn. nov., M. meretrix Lacordaire, 1848, syn. nov.); M. luctuosa Lacordaire, 1848 (=M. iracunda Lacordaire, 1848, syn. nov.); M. microcephala Lacordaire, 1848 [=M. tosta (Monros, 1950), syn. nov.]; M. notabilis notabilis Lacordaire, 1848 (=M. notabilis linearis Moldenke, 1970, syn. nov.); M. pyropiga pyropiga Lacordaire, 1848 (=M. pyropiga chiapensis Moldenke, 1970, syn. nov.); M. querula Lacordaire, 1848 (=M. propinqua Lacordaire, 1848, syn. nov., M. univittata pacifica Monros, 1953a, syn. nov.); M. religiosa Lacordaire, 1848 (=M. distincta Lacordaire, 1848, syn. nov.); M. splendida splendida Lacordaire, 1848 (=M. splendida affinis Jacoby, 1888, syn. nov.; M. splendida regalis Achard, 1926, syn. nov.); M. subfasciata subfasciata (LeConte, 1868) [= M. subfasciata majorubrofasciata Moldenke, 1970, syn. nov.; M. subfasciata murina (Monros, 1952), syn. nov.]; M. tricincta (Germar, 1824) (=M. bubalus bubalus Lacordaire, 1848 syn. nov., M. bubalus bubaloides Monros, 1953a, syn. nov.); M. univittata Lacordaire, 1848 (=M. univittata oblita Monros, 1953a, syn. nov.); M. viridana Lacordaire, 1848 (=M. metallica Jacoby, 1888, syn. nov.). Type designations: lectotypes are designated for the following species: M. anachoreta Lacordaire, 1848; M. chalybeosoma Lacordaire, 1848; M. coerulea Baly, 1877a; M. cornuta Lacordaire, 1848; M. dimidiata Lacordaire, 1848; M. flavipennis Jacoby, 1880; M. flavocincta Lacordaire, 1848; M. gazella Lacordaire, 1848; M. gigas Lacordaire, 1848; M. interruptofasciata Baly, 1877a; M. luctuosa Lacordaire, 1848; M. notabilis Lacordaire, 1848; M. obesa Lacordaire, 1848; M. placida Baly, 1877b; M. pyropiga Lacordaire, 1848; M. religiosa Lacordaire, 1848; M. splendida Lacordaire, 1848; M. subfasciata (LeConte, 1868); M. tricincta (Germar, 1824); M. unicincta Lefevre, 1884; M. univittata Lacordaire, 1848; M. viridana Lacordaire, 1848; M. microcephala Lacordaire, 1848. PMID- 25113597 TI - Shared but overlooked: 30 species of Holarctic Microlepidoptera revealed by DNA barcodes and morphology. AB - This study reports 30 species of Lepidoptera previously known from either the Palearctic or the Nearctic that are newly recorded as Holarctic. For 28 of these species, their intercontinental distributions were initially detected through DNA barcode analysis and subsequently confirmed by morphological examination; two Palearctic species were first detected in North America through morphology and then barcoded. When possible, the origin and status of each species (introduced, overlooked Holarctic species, or unknowingly re-described) is discussed, and its morphology is diagnosed and illustrated. The species involved include Tineidae: Scardia amurensis Zagulajev, Triaxomera parasitella (Hubner), Nemapogon cloacella (Haworth), Elatobia montelliella (Schantz), Tinea svenssoni Opheim; Gracillariidae: Caloptilia suberinella (Tengstrom), Parornix betulae (Stainton); Phyllonorycter maestingella (Muller); Yponomeutidae: Paraswammerdamia albicapitella (Scharfenberg), P. conspersella (Tengstrom); Plutellidae: Plutella hyperboreella Strand; Lyonetiidae: Lyonetia pulverulentella Zeller; Autostichidae: Oegoconia deauratella (Herrich-Schaffer), O. novimundi (Busck); Blastobasidae: Blastobasis glandulella (Riley), B. maroccanella (Amsel), B. tarda Meyrick; Depressariidae: Agonopterix conterminella (Zeller), Depressaria depressana (F.); Coleophoridae: Coleophora atriplicis Meyrick, C. glitzella Hofmann, C. granulatella Zeller, C. texanella Chambers, C. vitisella Gregson; Scythrididae: Scythris sinensis (Felder & Rogenhofer); Gelechiidae: Altenia perspersella (Wocke), Gnorimoschema jalavai Povolny, Scrobipalpa acuminatella (Sircom), Sophronia gelidella Nordman; Choreutidae: Anthophila fabriciana (L.); and Tortricidae: Phiaris bipunctana (F.). These cases of previously unrecognized faunal overlap have led to their redescription in several instances. Five new synonyms are proposed: Blastobasis glandulella (Riley, 1871) = B. huemeri Sinev, 1993, syn. nov.; B. tarda Meyrick, 1902 = Neoblastobasis ligurica Nel & Varenne, 2004, syn. nov.; Coleophora atriplicis Meyrick, 1928 = C. cervinella McDunnough, 1946, syn. nov.; C. texanella Chambers, 1878 = C. coxi Baldizzone & van der Wolf, 2007, syn. nov., and = C. vagans Walsingham, 1907, syn. nov. Lectotypes are designated for Blastobasis tarda Meyrick and Coleophora texanella Chambers. Type specimens were examined where pertinent to establish new synonymies. We identify 12 previously overlooked cases of species introductions, highlighting the power of DNA barcoding as a tool for biosurveillance. PMID- 25113599 TI - Facile synthesis of 5-hydroxy-L-lysine from D-galactose as a chiral-precursor. AB - A concise synthesis of (2S,5R) and (2S,5S)-5-hydroxy-lysine was achieved by utilizing D-galactose as a chiral-precursor with stereo retention. This synthetic strategy showcased the potential of utilizing carbohydrates as starting materials to prepare amino acids. Using the diazido intermediate, the derived beta-D galactopyranosyl and alpha-D-glucopyranosyl-(1->2)-beta-D-galactosyl moieties were synthesized. PMID- 25113598 TI - Fixed-target protein serial microcrystallography with an x-ray free electron laser. AB - We present results from experiments at the Linac Coherent Light Source (LCLS) demonstrating that serial femtosecond crystallography (SFX) can be performed to high resolution (~2.5 A) using protein microcrystals deposited on an ultra-thin silicon nitride membrane and embedded in a preservation medium at room temperature. Data can be acquired at a high acquisition rate using x-ray free electron laser sources to overcome radiation damage, while sample consumption is dramatically reduced compared to flowing jet methods. We achieved a peak data acquisition rate of 10 Hz with a hit rate of ~38%, indicating that a complete data set could be acquired in about one 12-hour LCLS shift using the setup described here, or in even less time using hardware optimized for fixed target SFX. This demonstration opens the door to ultra low sample consumption SFX using the technique of diffraction-before-destruction on proteins that exist in only small quantities and/or do not produce the copious quantities of microcrystals required for flowing jet methods. PMID- 25113600 TI - Endogenous peptide ligand-receptor systems for diverse signaling networks in plants. AB - Endogenous peptide ligand-receptor systems regulate cell-cell communications in various developmental processes in plants. Recent studies have revealed that the peptide-receptor combinations are not simply one-on-one with single roles. One peptide activates multiple downstream signaling through different receptors, while one receptor transmits different signals depending on peptide partners. Peptide signaling pathways also crosstalk with signaling pathways of phytohormones such as auxin, cytokinin and brassinosteroids. Furthermore, environmental cues such as temperature, nutrient, and microbes activate or inactivate peptide signaling pathways, which in turn modulate developmental processes. This report summarizes recent advance on peptide-receptor signaling, which makes a signaling network with phytohormone signaling pathways and environmental responses. PMID- 25113602 TI - Two coordination polymers constructed from a multidentate carboxylic acid ligand with a tertiary amine serve as acid-base catalysts for the synthesis of chloropropene carbonate from CO2 under atmospheric pressure. AB - Two new coordination polymers, [Ni(H2O)(Hpdcd)(H2O)2].DMF (1) and [Co(H2O)(Hpdcd)(H2O)2].DMF (2) (H3pdcd = 1-(4-carboxyphenyl)-2,5-dimethyl, 1H pyrrole-3,4-dicarboxylic acid), which were designed based on a tertiary amine ligand, were synthesized and characterized using multiple spectroscopy techniques, including single-crystal X-ray diffraction. These two 1D linear chains possess the properties of both a Lewis acid and organic base, which was confirmed by temperature programmed desorption of ammonia and on-line mass spectrometry (NH3-TPD-MS), and selective sorption for carbon dioxide. Due to their acid-base properties, the compounds exhibited high catalytic activity, in the absence of co-catalysts, for solvent-free synthesis of chloropropene carbonate from CO2 and epichlorohydrin under atmospheric CO2 pressure. The yields of chloropropene carbonate were 88% and 87% for 1 and 2, respectively, under the optimized conditions. PMID- 25113603 TI - An algorithm for score aggregation over causal biological networks based on random walk sampling. AB - BACKGROUND: We recently published in BMC Systems Biology an approach for calculating the perturbation amplitudes of causal network models by integrating gene differential expression data. This approach relies on the process of score aggregation, which combines the perturbations at the level of the individual network nodes into a global measure that quantifies the perturbation of the network as a whole. Such "bottom-up" aggregation relates the changes in molecular entities measured by omics technologies to systems-level phenotypes. However, the aggregation method we used is limited to a specific class of causal network models called "causally consistent", which is equivalent to the notion of balance of a signed graph used in graph theory. As a consequence of this limitation, our aggregation method cannot be used in the many relevant cases involving "causally inconsistent" network models such as those containing negative feedbacks. FINDINGS: In this note, we propose an algorithm called "sampling of spanning trees" (SST) that extends our published aggregation method to causally inconsistent network models by replacing the signed relationships between the network nodes by an appropriate continuous measure. The SST algorithm is based on spanning trees, which are a particular class of subgraphs used in graph theory, and on a sampling procedure leveraging the properties of specific random walks on the graph. This algorithm is applied to several cases of biological interest. CONCLUSIONS: The SST algorithm provides a practical means of aggregating nodal values over causally inconsistent network models based on solid mathematical foundations. We showed its utility in systems biology, where the nodal values can be perturbation amplitudes of protein activities or gene differential expressions, while the networks can be models of cellular signaling or expression regulation. Since the SST algorithm is based on general graph-theoretical considerations, it is scalable to arbitrary graph sizes and can potentially be used for performing quantitative analyses in any context involving signed graphs. PMID- 25113604 TI - PI3K, MAPK EPK1/2 and p38 are involved in the realization of growth potential of mesenchymal progenitor cells under the influence of basic fibroblast growth factor. AB - We studied PI3K, MAPK/EPK1/2 and p38-dependent signaling cascade under stimulation of the functions of mesenchymal progenitor cells by fibroblast growth factor. The important role of PI3K and EPK1/2 in the realization of their growth potential has been revealed. Experiments have demonstrated a blocking effect of PI3K inhibitor on proliferation and differentiation of progenitor cells and EPK1/2 inhibitor on mitotic activity of the progenitor cells. The p38-mediated MAPK pathway did not play a role in determining the proliferative and differentiation status of fibroblast CFU. PMID- 25113601 TI - 17beta-estradiol differentially regulates stress circuitry activity in healthy and depressed women. AB - Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17beta-estradiol (E2) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E2 during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E2 conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E2 modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E2 conditions were attenuated under high E2 conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced sex difference in MDD risk. PMID- 25113605 TI - Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord. AB - Changes in functional and metabolic activities of the brain were evaluated by EEG and positron-emission/computer tomography with 18F-fluorodeoxyglucose in patients with neuropathic pain syndrome previous to and 3 months after implantation of a system for chronic epidural spinal cord stimulation. In most cases, the use of a nerve stimulator was followed by alleviation of neuropathic pain and partial normalization of functional and metabolic activities of brain structures responsible for pain perception, emotiogenic, behavioral, and autonomic responses. PMID- 25113607 TI - Relationship between brain natriuretic peptides and recurrence of atrial fibrillation after successful direct current cardioversion: a meta-analysis. AB - BACKGROUND: Atrial fibrillation (AF) recurrence is common after successful direct current cardioversion (DCCV), with a 40% rate of recurrence within the first month. Several studies have investigated the potential association between brain natriuretic peptide (BNP) or N-terminal (NT)-proBNP levels before DCCV and the risk of AF recurrence, but results have been inconsistent. We, therefore, conducted a systematic review and meta-analysis of all available data to determine whether sinus rhythm (SR) maintenance after successful DCCV may be determined by preprocedural BNP and NT-proBNP levels. METHODS: We systematically searched Scopus, the Cochrane library, EMBASE, and MEDLINE databases to identify publications evaluating BNP or NT-proBNP levels in relation to post-DCCV AF recurrence, indexed from inception to September 2013. Among the initial 1,067 citations, 18 studies fulfilled the specified criteria. The difference in BNP and NT-proBNP concentrations in the AF recurrence and the SR-maintaining group was estimated by the standardized mean difference and the estimates of the pooled outcomes were evaluated using random-effects models. RESULTS: Baseline BNP levels in the AF recurrence group were significantly higher compared to BNP levels in the SR-maintaining group (standardized mean difference [SMD] -1.51, confidence interval [CI] [-2.53, -0.48], P = 0.004). Similar results were observed for NT proBNP levels, which were significantly higher in the AF recurrence group compared with the SR-maintaining group (SMD -0.63, CI [-1.13, -0.14], P = 0.01). CONCLUSIONS: Our analysis suggests that low preprocedural BNP/NT-proBNP levels are associated with SR maintenance. The use of BNP or NT-proBNP for prediction of long-term response to DCCV appears to be useful and should be further evaluated. PMID- 25113608 TI - Developmental profiles of GFAP-positive astrocytes in sheep cerebellum. AB - Astroglial account for the largest glial population in the brain and play a variety of vital functions in the development of the central nervous system (CNS). An immunohistochemical study was performed in 19 ovine foetuses ranging from 2 to 5 months of gestation, one newborn lamb and three adult sheep. Using the anit-glial fibrillary acidic protein (GFAP) marker, several variations were found in the degree of GFAP positive (GFAP+) astrocyte distribution between the different zones in the cerebellum of sheep during brain development. Our study indicates that the first appearance of astrocytes from restricted zones in the cerebellum occurs around the eighth week of gestation. Bergmann cells were found to be present from around the 15th week of gestation onwards. Our findings suggest that the maturation of astrocytes begins in the caudal parts of the cerebellum, developing from their initial ventral regions to spread first to dorsal regions radially within the white matter, then followed by the more rostral parts of the cerebellum. Astrocytes were also found to proliferate in the vermis before appearing in the cerebellar hemispheres. PMID- 25113610 TI - Systematic review and meta-analysis on the efficacy of selective laser trabeculoplasty in open-angle glaucoma. AB - Selective laser trabeculoplasty (SLT) is a relatively new type of laser used in treating open-angle glaucoma (OAG) and is reported to be equally efficacious to a first-line medication and argon laser trabeculoplasty (ALT). We summarize available evidence for considering SLT as an alternative treatment in OAG through systematic review and meta-analysis. Among OAG patients who range from newly diagnosed to those on maximally tolerated medical therapy, SLT results in a 6.9 35.9% intraocular pressure (IOP) reduction. Complications are rare and include an IOP spike requiring surgery, persistent macular edema, and corneal haze and thinning. Meta-analysis of randomized, controlled trials shows that SLT is non inferior to ALT and medication in IOP reduction and also in achieving treatment success. Number of medications reduction is similar between SLT and ALT. More robust evidence is needed to determine its efficacy as a repeated procedure. PMID- 25113606 TI - Spatial patterns of neuronal activity in rat cerebral cortex during non-rapid eye movement sleep. AB - It is commonly assumed that cortical activity in non-rapid eye movement sleep (NREMS) is spatially homogeneous on the mesoscopic scale. This is partly due to the limited observational scope of common metabolic or imaging methods in sleep. We used the recently developed technique of thallium-autometallography (TlAMG) to visualize mesoscopic patterns of activity in the sleeping cortex with single-cell resolution. We intravenously injected rats with the lipophilic chelate complex thallium diethyldithiocarbamate (TlDDC) during spontaneously occurring periods of NREMS and mapped the patterns of neuronal uptake of the potassium (K+) probe thallium (Tl+). Using this method, we show that cortical activity patterns are not spatially homogeneous during discrete 5-min episodes of NREMS in unrestrained rats-rather, they are complex and spatially diverse. Along with a relative predominance of infragranular layer activation, we find pronounced differences in metabolic activity of neighboring neuronal assemblies, an observation which lends support to the emerging paradigm that sleep is a distributed process with regulation on the local scale. PMID- 25113609 TI - Palinopsia revamped: a systematic review of the literature. AB - Palinopsia, the persistence or recurrence of visual images after the stimulus has been removed, is a nonspecific term that describes multiple types of visual symptoms with a wide variety of etiologies. For example, palinopsia may be the presenting symptom of a potentially life-threatening posterior cortical lesion, yet it may also be a benign medication side effect. We comprehensively review all published cases and subdivide palinopsia into two clinically relevant categories: illusory palinopsia and hallucinatory palinopsia. PMID- 25113611 TI - Systematic review of 342 cases of endogenous bacterial endophthalmitis. AB - We review a total of 342 cases of endogenous bacterial endophthalmitis reported between 1986 and 2012. Predisposing conditions were present in 60%, most commonly diabetes, intravenous drug use, and malignancy. The most common sources of infection were liver, lung, endocardium, urinary tract, and meninges. Systemic features such as fever were present in 74%, hypopyon in 35%, and an absent fundal view in 40%. Diagnostic delay occurred in 26%. Blood cultures were positive in 56%, and at least one intraocular sample was positive in 58% (comprising 26% anterior chamber samples, 59% vitreous taps, and 41% vitrectomy specimens). Worldwide, Gram negative infections (55%) were more frequent than Gram positive (45%) infections, particularly in Asia. Over the last decade, 11% of eyes were treated with systemic antibiotics alone, 10% intravitreal antibiotics alone, 36% systemic plus intravitreal antibiotics, and 20% systemic plus intravitreal antibiotics plus pars plana vitrectomy. The most commonly used intravitreal antibiotics were vancomycin (for Gram positive infection) and ceftazidime (Gram negative). The median final visual acuity was 20/100, with 44% worse than 20/200. Among all cases, 24% required evisceration or enucleation, and mortality was 4%. Both intravitreal dexamethasone and vitrectomy were each associated with a significantly greater chance of retaining 20/200 or better and significantly fewer eviscerations or enucleations-these warrant further study. For most patients, treatment should include a thorough systemic evaluation and prompt intravitreal and systemic antibiotics. PMID- 25113612 TI - Acoustic reflectors are visible in the right heart during radiofrequency ablation of varicose veins. AB - OBJECTIVE: Cerebrovascular events have been noted after foam sclerotherapy for varicose veins. One hypothesis is migration of microemboli to the brain through a cardiac septal defect. The aim of this study was to identify whether acoustic reflectors are found in the right side of the heart during radiofrequency ablation of varicose veins, as neurological events are not reported during these procedures. METHODS: Transthoracic echocardiography was performed during local anaesthetic radiofrequency ablation (VNUS ClosureFast) of the great saphenous vein in 14 patients. An apical view was captured at the start of the procedure, during each cycle of heating and at 1 min post-treatment. Patients were monitored for 1 h. Video loops were read by an independent cardiologist. The presence of acoustic reflectors was classified as: 0 = absent, 1 = occasional, 2 = stream, 3 = complete opacification. RESULTS: Loops were of diagnostic quality in 11/14 (79%) patients. After the second cycle of heating, acoustic reflectors moving through the right heart were seen in 5/11 (45%) patients. These were classified as grade 1 in four patients and grade 2 in one patient. No acoustic reflectors were seen in the left heart. No neurological symptoms were reported. CONCLUSION: Acoustic reflectors in the right heart are a common finding during radiofrequency ablation of varicose veins. Considering the prevalence of cardiac septal defects (17%), more neurological events would be expected if these particles were indeed responsible for these events. Further work is required to elicit the mechanisms underlying neurological complications following sclerotherapy. PMID- 25113613 TI - Synthesis and role of salicylic acid in wheat varieties with different levels of cadmium tolerance. AB - Wheat genotypes with different endogenous SA contents were investigated, in order to reveal how cadmium influences salicylic acid (SA) synthesis, and to find possible relationships between SA and certain protective compounds (members of the antioxidants and the heavy metal detoxification system) and between the SA content and the level of cadmium tolerance. Cadmium exposure induced SA synthesis, especially in the leaves, and it is suggested that the phenyl propanoid synthesis pathway is responsible for the accumulation of SA observed after cadmium stress. Cadmium influenced the synthesis and activation of protective compounds to varying extents in wheat genotypes with different levels of tolerance; the roots and leaves also responded differently to cadmium stress. Although a direct relationship was not found between the initial SA levels and the degree of cadmium tolerance, the results suggest that the increase in the root SA level during cadmium stress in the Mv varieties could be related with the enhancement of the internal glutathione cycle, thus inducing the antioxidant and metal detoxification systems, which promote Cd stress tolerance in wheat seedlings. The positive correlation between certain SA-related compounds and protective compounds suggests that SA-related signalling may also play a role in the acclimation to heavy metal stress. PMID- 25113615 TI - Static headspace-multicapillary column with gas chromatography coupled to ion mobility spectrometry as a simple approach for the discrimination of crude and processed traditional Chinese medicines. AB - The processing procedure can alter the nature and chemical transformation of traditional Chinese medicine to accommodate different clinical dispensing and preparation requirements. In this study, static headspace-multicapillary column with gas chromatography coupled to ion mobility spectrometry was developed for the rapid and sensitive discrimination of crude and processed traditional Chinese medicine. Using Radix Paeoniae Alba as a traditional Chinese medicine model, the combined power of this approach was illustrated by classifying the crude and processed Radix Paeoniae Alba samples into two main categories. The contents of the main components in Radix Paeoniae Alba varied significantly. The established method could promote the use of ion mobility spectrometry in intrinsic quality control and differentiation of herbal medicines from other processed products or preparations. PMID- 25113614 TI - Effect of paddy-upland rotation on methanogenic archaeal community structure in paddy field soil. AB - Methanogenic archaea are strict anaerobes and demand highly reduced conditions to produce methane in paddy field soil. However, methanogenic archaea survive well under upland and aerated conditions in paddy fields and exhibit stable community. In the present study, methanogenic archaeal community was investigated in fields where paddy rice (Oryza sativa L.) under flooded conditions was rotated with soybean (Glycine max [L.] Merr.) under upland conditions at different rotation histories, by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) and real-time quantitative PCR methods targeting 16S rRNA and mcrA genes, respectively. Soil samples collected from the fields before flooding or seeding, during crop cultivation and after harvest of crops were analyzed. The abundance of the methanogenic archaeal populations decreased to about one-tenth in the rotational plots than in the consecutive paddy (control) plots. The composition of the methanogenic archaeal community also changed. Most members of the methanogenic archaea consisting of the orders Methanosarcinales, Methanocellales, Methanomicrobiales, and Methanobacteriales existed autochthonously in both the control and rotational plots, while some were strongly affected in the rotational plots, with fatal effect to some members belonging to the Methanosarcinales. This study revealed that the upland conversion for one or longer than 1 year in the rotational system affected the methanogenic archaeal community structure and was fatal to some members of methanogenic archaea in paddy field soil. PMID- 25113616 TI - Anthropometric and craniofacial sexual dimorphism in obstructive sleep apnea patients: is there male-female phenotypical convergence? AB - Obstructive sleep apnea (OSA) is more common in men than women. Body size is greater in males (sexual dimorphism), but large body habitus is associated with OSA for both genders. We speculated that male-female phenotypical convergence (reduced sexual dimorphism via identical phenotype acquisition) occurs with OSA and tested hypotheses: (1) phenotypical features pathogenic for OSA differ between OSA and healthy subjects irrespective of gender; and (2) such characteristics exhibit phenotypical convergence. Utilizing an existing database, we calculated male-female (group average) ratios for eight anthropometric and 33 surface cephalometric variables from 104 Caucasian OSA patients [72 males; apnea hypopnea index (events h(-1) ): males: 42.3 +/- 24.7 versus females: 42.6 +/- 26.1 (P > 0.9)] and 85 Caucasian, healthy, non-OSA, community volunteers (36 males). Log-transformed data were analysed using a general linear model with post hoc unpaired t-tests and significance at P < 0.0012 (Bonferroni multiple comparison correction). OSA patients were older (56.9 +/- 14.4 versus 38.0 +/- 13.8 years), but there were no within-group gender-based age differences. All anthropometric variables (except height), plus cranial base width, mandibular breadth and retromandibular width diagonal were larger in gender-matched OSA versus healthy comparisons; thus satisfying hypothesis (1). Male-female ratios were mostly >1.0 across groups, but with no significant group * gender interactions no variable satisfied hypothesis (2). Thus, in this exploratory study, OSA patients had gender-common phenotypical differences to healthy subjects, but sexual dimorphism was preserved. Lack of complete phenotypical convergence may indicate gender-based critical phenotype-level attainment for OSA and/or gender-based OSA prevalence arises from factors other than those in this study. PMID- 25113617 TI - N-alkylacylamides in thin films display infrared spectra of 310-, alpha-, and pi helices with visible static and dynamic growth phases. AB - A peptide model is a physical system containing a CONH group, the simplest being HCONHCH3 , N-methylformamide (NMF). We have discovered that NMF and N methylacetamide (NMA), which form hydrogen-bonded oligomers in thin films on a planar AgX fiber, display infrared (IR) spectra with peaks like those of polypeptide helices. Structures can be assigned by their amide I maxima near 1672 (3(10)), 1655 (3(10)), 1653 (alpha), 1655 (pi), and 1635 cm(-1) (pi), which are the first IR data for the pi-helix. Sharp peaks are an outcome of immobilization of polar species on the polar surface of silver halides. We report the first use of expanded thin-film IR spectroscopy, in which plots of every spectrum over the amide I-II range show pauses or slow stages in the increase or decrease of absorption. These are identified as static phases followed by dynamic phases, with the incremental gain or loss of a helix turn. A general theory can be stated for such processes. Density functional calculations show that the NMA alpha-helix pentamer (crystal structure geometry) is transformed into a pi-helix-like form. For the first time, an entire sequence (3(10)-helix, alpha-helix, pi-helix, quasiplanar species) of spectra has been recorded for NMA. PMID- 25113618 TI - The gene expression profile of cumulus cells reveals altered pathways in patients with endometriosis. AB - PURPOSE: The objective of this experimental study was to compare the global gene expression profile of CC of mature oocytes in 18 patients with severe endometriosis and CC in 18 control patients affected by a severe male factor. METHODS: For each group, the CC were pooled, RNA was extracted and a microarray performed. For validating the microarray, a quantitative real-time PCR was performed in the CC of an independent set of patients with endometriosis (n = 5) and controls (n = 7). RESULTS: 595 differentially expressed genes (320 down regulated, 275 up-regulated, p < 0.05, fold change >=1.5) were identified. The most significant changes were observed in genes involved in the chemokine signaling and cell-cell or cell-extracellular matrix adhesion pathways. Several genes of these pathways were down-regulated in endometriosis. Individual RT-PCR assays confirmed the microarray for ten genes. CONCLUSIONS: Several genes involved in the chemokine mediated-signaling pathway and in the functional cross talk between CC and the oocyte are down-regulated in endometriosis CC. The impairment of these processes could explain the reduction of oocyte competence in endometriosis. This preliminary knowledge could be the starting point for a more detailed elucidation of the relationship between endometriosis and oocyte competence. PMID- 25113619 TI - Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin. AB - PURPOSE: The purpose of this study was to evaluate the oxidative stress status (OS) of follicular fluid (FF) and the oocyte quality in women with polycystic ovary syndrome (PCOS) undergoing different ovarian stimulation protocols. METHODS: FF samples were collected after gonadotropin administration in association or not with metformin or D-chiro-inositol (DCI). OS status was then evaluated by checking the follicular fluid protein oxidation profile after specific labeling of aminoacidic free-SH groups, and two-dimensional electrophoresis followed by qualitative and semiquantitative analysis. Oocyte quality was assessed by international morphological criteria. RESULTS: Our data indicated that both treatments, even if to different extent, recovered a significantly high level of free-SH groups in FF proteins of PCOS women clearly indicating a decrease of OS level with respect to that found in FF samples from gonadotropins alone treated women. A higher number of good quality MII oocytes was also observed in DCI (P < 0.05) or metformin (P < 0.05) study groups in comparison to untreated control group. CONCLUSION: A natural supplement and a drug both showed a statistically significant positive effect on follicular milieu by decreasing the oxidative damage on FF proteins, as well as in recovering good quality oocytes. PMID- 25113621 TI - Clinical pregnancy in a woman with idiopathic hypogonadotropic hypogonadism and low AMH: utility of ovarian reserve markers in IHH. AB - OBJECTIVE: Serum anti-mullerian hormone (AMH) has been proposed as a useful marker of ovarian reserve that is cycle-independent and predictive of outcome in assisted reproduction cycles. However, there is evidence that AMH production is gonadotropin-dependent, and that under the influence of FSH, growing follicles contribute to circulating AMH levels. Therefore, AMH testing may not be universally reflective of the primordial follicle pool in certain conditions. We demonstrate that in patients with idiopathic hypogonadotropic hypogonadism (IHH) and deficient gonadotropin production, AMH and antral follicle count (AFC) may not be reliable markers of ovarian reserve. DESIGN: Case report. SETTING: Fertility clinic at a tertiary academic hospital. PATIENT: A 30-year-old nulligravid patient with IHH who presented for fertility treatment with low FSH (0.3 IU/L), LH (0.1 IU/L), estradiol (77 pmol/L) and AMH levels (0.65 pmol/L), and an unmeasurable AFC. INTERVENTION: A three-month course of priming with oral micronized 17beta-estradiol, followed by daily injections of human menopausal gonadotropins (hMG). MAIN OUTCOME MEASURE: AMH level and follicular development. RESULTS: After 60 days of stimulation with hMG, the patient's AMH level increased to a peak of 1.27 pmol/L. After 102 days of stimulation, her estradiol level rose to 480 pmol/L and a 19 mm dominant follicle was detected. The patient successfully conceived with intrauterine insemination. CONCLUSION: Ovarian reserve testing in patients with IHH can be challenging due to the contracted appearance of the ovaries and deficient FSH production. In these patients, AMH levels may underestimate ovarian reserve due to the lack of FSH-dependent growing follicles. When treated with a long course of hMG, these patients may exhibit increased AMH levels and demonstrate adequate follicular development. PMID- 25113622 TI - Controlling adverse and beneficial effects of solar UV radiation by wearing suitable clothes - spectral transmission of different kinds of fabrics. AB - Humans should avoid prolonged exposure to the Sun during the warm subperiod of the year with naturally high solar UV level. One of the known recommendations to avoid excessive UV radiation is wearing clothes with UV protection additives. However there is an important question: how do we get an adequate solar UV radiation, which maintains a healthy status of vitamin D, without facing overexposure risks? It is found that some kind of 100% cotton knitted fabric, used in the production of normal daily clothing, has ~15% transmittance of solar UV. Model studies show that a garment made of this fabric allows larger synthesis of vitamin D3 in human body without the erythema risks (skin redness). Thus the adequate level of vitamin D could be attained safely by a person exposing only small part of the body (face, palms) during the period (May-August) of the year. PMID- 25113620 TI - Effects of group culture on the development of discarded human embryos and the construction of human embryonic stem cell lines. AB - PURPOSE: To explore the effect of group culture on the developmental potential of discarded embryos in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles and establish the human embryonic stem cell lines for future research. METHORDS: Fresh discarded embryos were collected from the IVF/ICSI-ET program in the reproductive medical center of the first affiliated hospital of Zhengzhou university in this study. All zygotes were individually cultured from Day 1 to Day 3. On Day 3, discard embryos were then cultured in group of 1-4 embryos per droplet (30 MUl/droplets) with a constant culture medium until Day 5 or 6. Mechanical method was used to isolate the inner cell mass (ICM) of blastocyst from the embryo. Then we inoculated the ICM on feeder layer. After identification of those cells, the human embryonic stem cell lines (hESCs) were established. RESULTS: In this study, we collected 1,223 fresh discarded embryos and they were sequential cultured to the blastocysts (18.07 %, 221/1,223), in which good quality blastocysts were 61(4.98 %, 61/1,223). There was no significant difference in the patients. The embryos from 1PN, 2PN, 3PN were sequential cultured to the blastocyst s(39.31 %,92/234;12.87 %,64/497;13.21 %,65/492),in which good quality blastocysts was 13.6 %(32/92),2.61 %(13/64), 3.04 %(15/65).1PN embryo's blastulation rate and quality embryo formation rate was significantly higher than the 2PN and 3PN embryos' (P <0.05). Three embryos group cultivation has the highest blastulation rate and quality embryo formation rate (P <0.05). In total, we successfully established 4 hESCs lines. CONCLUSION: The group culture of human discard embryos can improve the blastulation rate and blastocyst quality to some extent. Three embryos group cultivate is the better culture number. Human discard embryos are good source for establishment of hESCs. PMID- 25113623 TI - Extramammary Paget's disease of the perianal region: a 20-year experience. AB - BACKGROUND: To evaluate the results obtained from cases of perianal Paget's disease (PPD) and to provide a current perspective in the diagnostic evaluation and surgical management of this condition. METHODS: A retrospective review of a single quaternary referral centre's experience with PPD from January 1994 to December 2013 was performed. Medical records were reviewed to collect data on demographics, preoperative investigations, complications, pathology and recurrence. A review of existing literature was also performed. RESULTS: Five patients (four females, one male) with histologically confirmed PPD were identified. The median age of presentation was 72 (range 61 to 78). Three patients were recurrences following previous excisions and first presentations in two patients. Only one patient had an underlying diagnosis of cancer. The median time to diagnosis was 24 months. Four patients underwent wide local excision with skin graft and/or local flap reconstruction and one patient required an abdominoperineal excision for recurrence. Four patients had involved lateral margins despite wide local excision but follow-up to date has only revealed one local recurrence. A review of available literature suggests that synchronous cancers can occur in up to 33% of patients and that a further 10% may be associated with metachronous cancers. Surveillance recommendations seem anecdotal and do not appear to be supported by available literature. CONCLUSION: PPD is a management challenge. Association with synchronous and metachronous carcinomas may not be as strong as initially thought. Surgery is the mainstay treatment with the need to balance between minimizing disease recurrence and functional sequelae from excessive tissue loss. PMID- 25113624 TI - A systematic review of the effectiveness of individual, community and societal level interventions at reducing socioeconomic inequalities in obesity amongst children. AB - BACKGROUND: Tackling childhood obesity is one of the major contemporary public health policy challenges and vital in terms of addressing socioeconomic health inequalities.We aimed to systematically review studies of the effectiveness of interventions (individual, community and societal) operating via different approaches (targeted or universal) in reducing socio-economic inequalities in obesity-related outcomes amongst children. METHODS: Nine electronic databases were searched from start date to October 2012 along with website and grey literature searches. The review examined the best available international evidence from interventions that aimed to prevent obesity, treat obesity, or improve obesity-related behaviours (diet and/or physical activity) amongst children (aged 0-18 years) in any setting and country, so long as they provided relevant information and analysis on both socioeconomic status and obesity related outcomes. Data extraction and quality appraisal were conducted using established mechanisms and narrative synthesis was conducted. RESULTS: We located 23 studies that provided the 'best available' (strongest methodologically) international evidence. At the individual level (n = 4), there was indicative evidence that screen time reduction and mentoring health promotion interventions could be effective in reducing inequalities in obesity. For the community level interventions (n = 17), evidence was inconclusive - with some studies suggesting that school-based health promotion activities and community-based group-based programmes were effective in reducing obesity - others not. Societal level evaluations were few (n = 1). However, there was no evidence to suggest that any of these intervention types increase inequalities and several studies found that interventions could at least prevent the widening of inequalities in obesity. The majority of studies were from America and were of 6-12 year old children. CONCLUSIONS: The review has found only limited evidence although some individual and community based interventions may be effective in reducing socio-economic inequalities in obesity-related outcomes amongst children but further research is required, particularly of more complex, societal level interventions and amongst adolescents. PMID- 25113625 TI - A semi-probabilistic modelling approach for the estimation of dietary exposure to phthalates in the Belgian adult population. AB - In this study, a semi-probabilistic modelling approach was applied for the estimation of the long-term human dietary exposure to phthalates--one of world's most used families of plasticisers. Four phthalate compounds were considered: diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), benzylbutyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP). Intake estimates were calculated for the Belgian adult population and several subgroups of this population for two considered scenarios using an extended version of the EN-forc model. The highest intake rates were found for DEHP, followed by DnBP, BBP and DEP. In the Belgian adult population, men and young adults generally had the highest dietary phthalate intake estimates. Nevertheless, predicted dietary intake rates for all four investigated phthalates were far below the corresponding tolerable daily intake (TDI) values (i.e. P99 intake values were 6.4% of the TDI at most), which is reassuring because adults are also exposed to phthalates via other contamination pathways (e.g. dust ingestion and inhalation). The food groups contributing most to the dietary exposure were grains and grain-based products for DEP, milk and dairy products for DnBP, meat and meat products or grains and grain-based products (depending on the scenario) for BBP and meat and meat products for DEHP. Comparison of the predicted intake results based on modelled phthalate concentrations in food products with intake estimates from other surveys (mostly based on measured concentrations) showed that the extended version of the EN-forc model is a suitable semi-probabilistic tool for the estimation and evaluation of the long-term dietary intake of phthalates in humans. PMID- 25113626 TI - Effect modification of ozone-related mortality risks by temperature in 97 US cities. AB - Many time-series studies have characterized the relationship between short-term ozone exposure and adverse health outcomes, controlling for temperature as a confounder. Temperature may also modify ozone effects, though this has been largely under-investigated. In this study, we explored whether temperature modifies the effect of short-term ozone exposure on mortality. We used the database developed for the National Morbidity and Mortality Air Pollution Study to estimate ozone mortality risks in 97 US cities in May through September, 1987 2000. We treated temperature as a confounder as well as an effect modifier by estimating risks at low, moderate, and high temperature categories. When temperature was treated as a confounder, a 10-ppb increase in daily 24-h ozone was associated with a 0.47% (95% CI: 0.19%-0.76%) increase in mortality. When we assessed effect modification by temperature, the interaction between ozone and temperature was not statistically significant. However, there was a U-shaped pattern in mortality risk, which was greater at the low (<25th percentile) and high (>75th percentile) temperature levels than moderate temperature levels. At the high temperature category, a 10% increase in AC prevalence mitigated mortality risk associated with 10-ppb of ozone exposure by -0.18% (95% CI: 0.35%, -0.02%). Furthermore, ozone mortality risk in the high temperature category increased as we restricted our analyses to hotter days. On days where temperatures exceeded the 75th, 90th, and 95th percentile temperatures, a 10-ppb increase in ozone was associated with a 0.65% (95% CI: 0.20%-1.09%), 0.83% (95% CI: 0.17%-1.48%), and 1.35% (95% CI: 0.44%-2.27%) increase in mortality, respectively. These results suggested that high temperatures may exacerbate physiological responses to short-term ozone exposure. PMID- 25113627 TI - Photosynthesis, chlorophyll fluorescence characteristics, and chlorophyll content of soybean seedlings under combined stress of bisphenol A and cadmium. AB - Bisphenol A (BPA) is ubiquitous in the environment because of its continual application in plastics and the epoxy resin industry. Cadmium (Cd) is a highly toxic heavy metal element mainly used in smelting, electroplating, and plastic and dye manufacturing. Pollution as a result of BPA and Cd exists simultaneously in many agricultural regions. However, little information is available regarding the combined effects of BPA and Cd on plants. The combined effects of BPA and Cd on the photosynthesis, chlorophyll fluorescence, and chlorophyll content of soybean seedlings were investigated using noninvasive technology. Combined treatment with 1.5 mg/L BPA and 0.2 mg/L Cd synergistically improved the net photosynthetic rate (Pn ), initial fluorescence (F0 ), maximal photochemical efficiency (Fv /Fm ), effective quantum yield of photosystem II (PhiPSII ), photosynthetic electron transport rate (ETR), and chlorophyll content. Combined treatment with 1.5 mg/L BPA and 3.0 mg/L Cd increased the F0 and decreased the Pn , Fv /Fm , PhiPSII , and ETR, whereas BPA and Cd exhibited an antagonistic effect. Furthermore, combined treatment with 17.2/50.0 mg/L BPA and 3.0/10.0 mg/L Cd synergistically decreased the Pn , Fv /Fm , PhiPSII , ETR, and chlorophyll content, although it increased the F0 . Finally, the effects of BPA and Cd on photosynthesis, chlorophyll fluorescence, and chlorophyll content ceased when BPA stress was stopped. PMID- 25113628 TI - Intranasally administered serelaxin abrogates airway remodelling and attenuates airway hyperresponsiveness in allergic airways disease. AB - BACKGROUND: The peptide hormone relaxin plays a key role in the systemic hemodynamic and renovascular adaptive changes that occur during pregnancy, which is linked to its antiremodelling effects. Serelaxin (a recombinant form of human gene-2 relaxin) has been shown to inhibit lung fibrosis in various disease models and reverse airway remodelling and airway hyperresponsiveness (AHR) in allergic airways disease (AAD). OBJECTIVE: Although continuous systemic delivery of exogenous serelaxin alleviates allergic fibrosis and AHR, more direct routes for administration into the lung have not been investigated. Thus, intranasal administration of serelaxin was evaluated for its ability to reverse airway remodelling and AHR associated with AAD. METHODS: Female Balb/c mice were subjected to a 9-week model of chronic AAD. Subgroups of animals (n = 12/group) were then treated intranasally with serelaxin (0.8 mg/mL) or vehicle once daily for 14 days (from weeks 9-11). Saline-sensitized/challenged mice treated with intranasal saline served as additional controls. Differential bronchoalveolar lavage (BAL) cell counts, ovalbumin (OVA)-specific IgE levels, tissue inflammation, parameters of airway remodelling and AHR were then assessed. RESULTS: Chronic AAD was associated with significant increases in differential BAL cell counts, OVA-specific IgE levels, inflammation, epithelial thickening, goblet cell metaplasia, TGF-beta1 expression, epithelial Smad2 phosphorylation (pSmad2), subepithelial collagen thickness, total lung collagen concentration and AHR (all P < 0.05 vs. respective measurements from saline-treated mice). Daily intranasal delivery of serelaxin significantly diminished AAD-induced epithelial thickening, epithelial pSmad2, subepithelial and total lung collagen content (fibrosis) and AHR (all P < 0.05 vs. vehicle-treated AAD mice). CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal delivery of serelaxin can effectively reduce airway remodelling and AHR, when administered once daily. Respirable preparations of serelaxin may have therapeutic potential for the prevention and/or reversal of established airway remodelling and AHR in asthma. PMID- 25113629 TI - Experimental investigation of the 2D ion beam profile generated by an ESI octopole-QMS system. AB - In this paper, we have employed an ion imaging approach to investigate the behavior of ions exiting from a quadrupole mass spectrometer (QMS) system that employs a radio frequency octopole ion guide before the QMS. An in-vacuum active pixel detector (Timepix) is employed at the exit of the QMS to image the ion patterns. The detector assembly simultaneously records the ion impact position and number of ions per pixel in every measurement frame. The transmission characteristics of the ion beam exiting the QMS are studied using this imaging detector under different operating conditions. Experimental results confirm that the ion spatial distribution exiting the QMS is heavily influenced by ion injection conditions. Furthermore, ion images from Timepix measurements of protein standards demonstrate the capability to enhance the quality of the mass spectral information and provide a detailed insight in the spatial distribution of different charge states (and hence different m/z) ions exiting the QMS. PMID- 25113630 TI - Subtotal supracricoid laryngectomy: changing in indications, surgical techniques and use of new surgical devices. AB - PURPOSE: The aim of this study is to evaluate the evolution of supracricoid partial laryngectomy (SCPL) in indications, surgical techniques and outcomes through last decades. MATERIALS AND METHODS: A retrospective analysis of 146 patients affected by laryngeal cancer treated with SCPL was carried on. We defined: (1) group A, 100 patients treated by cold instruments between 1995 and 2004; (2) group B, 46 patients treated by harmonic scalpel between 2005 and 2010. Complications rate, and functional and oncological results were documented and a comparison between the two groups was made; histopathological analysis of surgical margins was evaluated and correlated with local incidence of recurrence. RESULTS: Significant differences in age mean-value (p=0.02), T classification (p=0.007), and in indication for more advanced-staged patients were found in group B (p=0.001). Surgical procedure was shorter in group B (p<0.001), with shorter swallowing recovery (p=0.003). Oncological outcomes did not report any significant differences. Group B showed a higher incidence of post- operative arytenoid edema (p=0.03) associated with a lower rate of pneumonia (p=0.038). Despite a higher rate of close or positive-margins found in group B no higher incidence of local-recurrence was reported (p=0.02) compared to group A. CONCLUSIONS: We documented changing in indications and surgical technique for SCPL because of the development of modern diagnostic techniques and the introduction of low-thermal injury device allowing a more challenging tumor excision as well as with a shorter swallowing recovery in our series. PMID- 25113631 TI - Long-term efficacy of inferior meatal antrostomy for treatment of postoperative maxillary mucoceles. AB - PURPOSE: Transnasal endoscopic marsupialization has replaced the conventional Caldwell-Luc operation for managing postoperative maxillary mucoceles. Inferior meatal antrostomy (IMA) may be an easier and more effective method than middle meatal antrostomy (MMA) because of anatomical and structural changes of the maxillary sinus. We evaluated the long-term efficacy and technical simplicity of both methods. METHODS: This study included 21 and 32 patients who underwent MMA and IMA, respectively. They were diagnosed with a unilateral postoperative maxillary mucocele, and medical records were reviewed for history, clinical presentation, radiographic findings, surgical intervention, complications, and outcomes. During follow-up, the size of the opening and stenosis or obstruction of the antrostomy site were evaluated. RESULTS: Preoperative symptoms and mean follow-up period were similar in both groups. All patients in the IMA group received the operation as planned, whereas in four MMA patients, the attempt to create an opening failed because of thick bones and anatomical changes from the previous operation; in these patients, IMA was performed. The opening remained large enough for ventilation and drainage between the mucocele and the nasal cavity in both groups. There were no major complications, such as profuse bleeding, wound infection, or orbital or nasolacrimal duct injury. CONCLUSIONS: Although both surgical procedures seem to be effective for managing postoperative maxillary mucoceles, IMA is easier to perform, and no instances of failure to create antrostomy openings occurred. We recommend IMA as the surgical technique of choice, but providing an opening of sufficient size is necessary to ensure long-term efficacy. PMID- 25113633 TI - Improving complex kinship analyses with additional STR loci. AB - In a standard paternity testing, mother, child, and alleged father are analyzed with STR markers using commercially available kits. Since Italian civil legislation does not have thresholds to confirm a paternity, paternity is practically proven when likelihood ratio increases prior probability of paternity to posterior, accepted by court as sufficient. However, in some cases the number of markers included in a commercial kit may be insufficient to conclusively prove or disprove a relationship between individuals, especially when complex family scenarios are suspected or indirect analyses are required. Additional genetic information can increase the values of the likelihood ratio regarding the detection of true parental relationships in a pedigree, while reducing the chances of false attributions (e.g. false paternities). In these cases the introduction of a 26Plex amplification system allows to examine 23-26 additional markers depending on the commercial kit used, thus increasing the statistical power of the kinship analysis. The PCR conditions were optimized for a multiplex amplification system and a new generation CE instrument. In order to demonstrate the utility of additional STRs markers, four complex kinship cases are presented. PMID- 25113632 TI - Linking mother and youth parenting attitudes: indirect effects via maltreatment, parent involvement, and youth functioning. AB - Evidence suggests that parenting attitudes are transmitted within families. However, limited research has examined this prospectively. The current prospective study examined direct effects of early maternal attitudes toward parenting (as measured at child age 4 by the Adult-Adolescent Parenting Inventory [AAPI]) on later youth parenting attitudes (as measured by the AAPI at youth age 18). Indirect effects via child maltreatment (physical abuse, sexual abuse, neglect, and emotional maltreatment), parent involvement, and youth functioning (internalizing and externalizing problems) were also assessed. Analyses were conducted on data from 412 families enrolled in the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). There were significant direct effects for three of the four classes of mother parenting attitudes (appropriate developmental expectations of children, empathy toward children, and appropriate family roles) on youth attitudes but not for rejection of punishment. In addition, the following indirect effects were obtained: Mother expectations influenced youth expectations via neglect; mother empathy influenced youth empathy via both parental involvement and youth externalizing problems; and mother rejection of punishment influenced youth rejection of punishment via youth internalizing problems. None of the child or family process variables, however, affected the link between mother and youth attitudes about roles. PMID- 25113634 TI - Weaknesses of histological analysis in celiac disease diagnosis: new possible scenarios. AB - INTRODUCTION: Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten. Serology and organ culture system can support CD diagnosis, despite histology being the gold standard. AIM: We wanted to test the uniformity of application of Marsh-Oberhuber criteria by five different histologists. We also compared histological and serological data with cultural results to consider new possible strategies in CD diagnosis. METHODS: We studied 114 patients, who were divided in two groups. Group A was composed of 66 patients on a gluten containing diet, with gluten-related signs and symptoms, showing positive serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase (anti- tTG). Group B was composed of 48 disease-control patients, presenting serological EMA and anti-tTG negative results. All patients studied underwent esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ culture. All histological samples were evaluated by five different histologists according to an appropriate questionnaire following Marsh-Oberhuber classification. Cohen kappa inter-test was used for evaluating the agreement between histologists regarding group A. RESULTS: Strength of agreement was fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A presented positive serological as well as cultural results in 100% of cases. None of the patients belonging to group B presented serological or cultural positive results. DISCUSSION: Our study stresses the limits of histological interpretation due to the lack of uniformity in the use of Marsh-Oberhuber classification. These findings could cast doubt on the role of histology as CD gold standard and could open a debate on the most appropriate CD diagnostic procedure. PMID- 25113635 TI - Host defense peptides: front-line immunomodulators. AB - Although first studied for their antimicrobial activity, host defense peptides (HDPs) are now widely recognized for their multifunctional roles in both the innate and adaptive immune responses. Their diverse immunomodulatory capabilities include the modulation of pro- and anti-inflammatory responses, chemoattraction, enhancement of extracellular and intracellular bacterial killing, cellular differentiation and activation of the innate and adaptive compartments, wound healing, and modulation of autophagy as well as apoptosis and pyroptosis. We review the various immunomodulatory roles of HDPs and their synthetic analogs, the innate defense regulators (IDRs). We discuss their potential as host-directed therapies, the hurdles they face in clinical development, and propose ways forward. PMID- 25113636 TI - Long non-coding RNAs in the regulation of the immune response. AB - It is increasingly clear that long non-coding RNAs (lncRNAs) regulate a variety biological responses, and that they do so by a diverse range of mechanisms. In the field of immunology, recent publications have shown widespread changes in the expression of lncRNAs during the activation of the innate immune response and T cell development, differentiation, and activation. These lncRNAs control important aspects of immunity such as production of inflammatory mediators, differentiation, and cell migration through regulating protein-protein interactions or via their ability to basepair with RNA and DNA. We review the current understanding of the mechanism of action of these immune-related lncRNAs, discuss their impact on physiological and pathological processes, and highlight important areas of inquiry at the intersection between immunology and lncRNA biology. PMID- 25113637 TI - Influence of the microbiota on vaccine effectiveness. AB - Studies of the relationship between the microbiome and the development and function of the immune system are demonstrating novel concepts that could significantly alter the way we treat disease and promote wellness. Several diseases, including inflammatory bowel disease, allergy/asthma, and diabetes, are associated with changes in composition of the microbiome. Recent findings suggest novel complex mechanisms by which the microbiome impacts immune cell development and differentiation. A major implication of these findings is that the composition of microbiome may ultimately affect vaccine efficacy. We explore here the potential role of the microbiome in vaccine responses in the context of our growing understanding of the relationship between the gastrointestinal microbiota, resident immune cell populations, and systemic immunity. PMID- 25113640 TI - Expression and localization of estrogen receptor in human breast cancer and its clinical significance. AB - The aim of this study was to analyze the clinicopathologic significance of ERalpha protein that localized in the cell cytoplasm and/or cell membrane of human breast cancer and explore what kind of protein that the cytoplasm/membrane ERalpha belongs to. ERalpha expressions in 61 cases of breast cancer are detected by immunohistochemistry, grouping is performed according to the positive staining of different subcellular localizations, the expression levels of ERalpha66 and ERalpha36 in cancer tissues of groups with different subcellular localizations are detected by Western blot, and correlation between the indicators and its clinicopathologic significance are analyzed by combining with the clinical pathological parameters. Localization by immunohistochemical staining in breast cancer cells shows that there are two types of ERalpha-in the cell nucleus and/or the cell membrane; there are four groups as ER nuclear staining positive + membrane staining positive (N+/C+), 23 cases; ER nuclear staining positive + membrane staining negative (N+/C-), 16 cases; ER nuclear staining negative + membrane staining positive (N-/C+), 8 cases; and ER nuclear staining negative + membrane staining negative (N+/C+), 14 cases. ER expression in the cytoplasm and/or membrane of cancer cells is correlated with the high expression of HER-2, the lymphatic metastasis, and the late clinical stage. Western blot results show that ER protein in breast cancer tissues mainly consists of ERalpha66 and ERalpha36 bands, and among all the groups, all the cases from the N+/C+ group (n = 23) have both ERalpha66 and ERalpha36 expressions; in the N+/C- group, 14 cases of which only have the ERalpha66 expression without ERalpha36 expression and 2 cases of which have both ERalpha66 and ERalpha36 expression; all the cases from the N-/C+ group have only the ERalpha36 expression without ERalpha66 expression; and in the N-/C- group, there is no either ERalpha66 or ERalpha36 expression. The expression level of ERalpha36 relates to the age of patients, the menopause, the lymphatic metastasis, and the tumor size (p < 0.05), and no statistical significance was shown between it and the family history of patients as well as the clinical staging parameters (p > 0.05). The expression level of ERalpha66 relates to the tumor size of breast cancer and the clinical stages (p < 0.05), and no statistical significance was shown between it and the age of patients, the history of menopause, and the family history as well as the parameters of lymphatic metastasis (p > 0.05). ER protein expression of human breast cancer is localized in the cell nucleus and/or the cell membrane, with poor prognosis of cytoplasm/membrane-positive patients; ER protein that localized in the nucleus is mainly ERalpha66 and that localized in the cytoplasm and/or membrane is mainly ERalpha36. PMID- 25113638 TI - Prostaglandin D2-supplemented "functional eicosanoid testing and typing" assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study. AB - BACKGROUND: Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. METHODS: Using the "functional eicosanoid testing and typing" (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA) , acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. RESULTS: We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 +/- 0.356 (range: 1.14-2.36), compared to 0.53 +/- 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 +/- 302.2 pg/ml versus 142 +/- 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 +/- 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. CONCLUSIONS: The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD. PMID- 25113641 TI - New insight into improvement of cardiovascular outcomes with intensive glycemic control in patients with metabolic syndrome and type 2 diabetes mellitus included. AB - The epidemiology of metabolic syndrome (MetS) is very concerning since this is a widespread chronic disease in adult and elderly population. Different epidemiological studies confirmed strong relationship between type 2 diabetes mellitus (DM2) inclusive MetS and the occurrence of microvascular and macrovascular complications in these patients. Therefore, we are discussing molecular mechanisms and pathways recently introduced and intensively researched. These molecules have been held responsible for direct and indirect correlative trends important in the assessment of potential benefit of intensive glycemic control. Novel substances may improve patient's outcome in recent future regarding cardiovascular complications though their acting mechanisms have not been completely elucidated. We are reviewing whether it would intensive glycemic control be a reasonable approach in patients with MetS when DM2 is included and which recommendations are currently widely applied. The aim was therefore to emphasize current need for further investigations in the field since the utility of intensive glycemic control in all DM/MetS patients as mean for reduction of cardiovascular complications still remains controversial. PMID- 25113639 TI - Tumor Necrosis Factor Alpha (-238 / -308) and TNFRII-VNTR (-322) Polymorphisms as Genetic Biomarkers of Susceptibility to Develop Cervical Cancer Among Tunisians. AB - Host genetic factors may confer susceptibility to Cervical Cancer. TNF-alpha as pro-inflammatory cytokine participates in the maintenance of immune homeostasis. Allelic variation of immuno-modulatory genes is associated with alteration in immune function. This study investigated the associations between TNF-alpha 308G>A, -238G>A, and TNFRII - VNTR-322 and cervical cancer in Tunisian women. Genotypes of those polymorphisms were detected in 130 cases and 260 controls. The variant heterozygote -308 G/A was associated with a 41% decreased risk of cervical cancer (GG vs A/A; p = 0.002; OR = 0.41; 95% CI =0.23-0.76). Furthermore, compared with dominant variant G/G, the (G/A+A/A) genotypes was significantly associated with a decreased risk of CC (GG vs G/A+A/A; p = 0.026; OR = 0.62; 95% CI = 0.40-0.97). The FIGO stratified analysis showed that the minor variant A/A and combined G/A+A/A of TNFalpha-238 G>A and TNFalpha-308 G>A increased the risk of the tumor evolution, respectively, (P = 0.011; OR = 2.98; 95% CI = 1.16-7.72) (P = 0.008; OR = 2.76; 95% CI = 1.20-6.41), (P = 0.000; OR = 16.33; 95% CI = (5.10-55.23) (P = 0.000; OR = 7.54; 95% CI = 2.68-22.29). There was statistically significant relationship between the incidence of the TNF-alpha mutations and the clinical progression of cancer according to the FIGO classification. In our study, the haploview analysis revealed no LD between rs1800629 and rs361525. TNF-alpha and TNFRII polymorphisms might be genetic risk factors for cervical cancer in Tunisian population. PMID- 25113642 TI - Relation of PAI-1 and TPA genes polymorphisms to acute myocardial infarction and its outcomes in Egyptian patients. AB - Endogenous fibrinolysis is a protective mechanism against arterial thrombotic occlusion, which would otherwise lead to permanent tissue damage as acute myocardial infarction (AMI). We aimed to investigate the association of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (TPA) genes polymorphisms with myocardial infarction and its outcomes in Egyptian patients. 184 patients with AMI and 184 controls were included in the study. PAI 1 and TPA genes polymorphisms were analyzed by polymerase chain reaction. All patients were followed for AMI complications during their hospitalization. We found a significant association among TPA ID, II genotypes, and I allele and increased risk of AMI by 2.1, 3.2, and 1.9 fold, respectively. Also, the frequencies of PAI-1 4G/4G genotype and 4G allele were significantly increased in patients with AMI as compared to the control group. Furthermore, AMI patients with PAI-1 4G/4G genotype were significantly more likely to have morbidity and mortality complications as compared to AMI patients without complications (P = 0.00 and 0.048, respectively). We concluded that 4G/4G genotype and 4G allele of the PAI-1 gene are associated with risk of AMI and its morbidity. The PAI-1 4G/4G genotype is associated with mortality of AMI. There is also an association between TPA ID, II genotypes, and I allele with increased risk of AMI. PMID- 25113643 TI - Posterior trochanteric osteotomy in acetabular fractures for 32 cases. AB - The aim of this study is to explore the method and clinical outcome of posterior trochanteric osteotomy in acetabular fractures. From January 2000 to January 2008, 32 cases of acetabular fractures involving the dome of acetabulum underwent posterior trochanteric osteotomy for a better exposure and internal fixation with acetabular tridimensional memory fixation system. 28 cases (16 men and 12 women, mean age 39.9 years, range 16-73 years) were followed up with an average of 48.9 months (range of 19-95 months) and four were lost during follow up. Of 28 cases, 19 were fresh fractures and 9 were old fractures. The reduction was evaluated with Matta criteria. Clinical evaluation was based on modified Merle d'Aubigne and Postel scoring. Motor strength of the abductors was evaluated according to the Medical Research Council grading system. Ectopic ossification was classified according to Brooker criteria. Anatomical reduction was achieved in 17 cases and satisfied reduction in 10 patients. Poor reduction happened in an old fracture. All acetabular fractures got a direct bone union and no displacement and deep infection occurred. All osteotomies healed within 3.5 months without any nonunion, proximal migration of the greater trochanter, loosing or broken of instrumentation, and deep infection. Two superficial infections were healed with a regular dressing. Two patients underwent removal of implants from greater trochanter because of irritation. The strength of the abductors was of Grade 3/5 in two patients, Grade 4/5 in five patients, and normal in the rest. Clinical scoring was excellent to good in 84 %. Ectopic ossification occurred in five patients, grade 1 in two patients, grade 2 in two, and grade 3 in one. But function of hip joint was not seriously affected. Posterior trochanteric osteotomy can provide an adequate exposure of the dome of acetabulum without the associated complications like nonunion, proximal replacement, and weak of the abductors which often occur with standard oblique osteotomy. PMID- 25113644 TI - Gold-catalyzed cycloisomerization of 1,6,8-dienyne carbonates and esters to cis cyclohepta-4,8-diene-fused pyrrolidines. AB - A synthetic approach that provides access to cis-cyclohepta-4,8-diene-fused pyrrolidines efficiently through Au(I) -catalyzed cycloisomerization of 1,6,8 dienyne carbonates and esters at a low catalyst loading of 2 mol % is reported. Starting carbonates and esters with a pendant alkyl group on the terminal alkenyl carbon center were found to favor tandem 1,2-acyloxy migration/cyclopropanation followed by Cope rearrangement of the resulting cis-3-azabicyclo[3.1.0]hexane intermediate. On the other hand, substrates containing a terminal diene or starting materials in which the distal alkene moiety bears a phenyl substituent were observed to undergo competitive but reversible 1,3-acyloxy migration prior to the nitrogen-containing bicyclic ring formation. The delineated reaction mechanism also provides experimental evidence for the reversible interconversion between the oft-proposed organogold intermediates obtained in this step of the tandem process. PMID- 25113645 TI - Aging and the novelty pressor effect in men on the first day of 7-day/24-hour ambulatory blood pressure monitoring. PMID- 25113646 TI - Elevated serum CA 19-9 at screening tests: underlying conditions and role of abdominopelvic CT. AB - OBJECTIVES: To investigate underlying conditions of patients with elevated CA 19 9 at screening tests and to evaluate diagnostic performance of abdominopelvic CT. METHODS: One hundred and thirteen patients with elevated CA 19-9 (>37 U/ml) who underwent abdominopelvic CT in a screening program were selected. Underlying conditions were determined by reviewing all available data and follow-up records. Patients were categorized into malignancy, benign, and normal/non-related disease groups. Their mean CA 19-9 and percent of patients with CA 19-9 >= 100 U/ml were compared. Diagnostic sensitivity of CT for detecting underlying conditions of elevated CA 19-9 was analysed. RESULTS: Seventeen patients (17/113, 15 %) had 17 elevated CA 19-9-related malignancies, and 55 patients (55/113, 48.7 %) had 70 benign diseases. Mean CA 19-9 and percent of patients with CA 19-9 >= 100 U/ml in the malignancy group were significantly higher than in the two other groups. CT detected all except one malignant lesion with a detection sensitivity of 94.1 % (16/17). Of 70 CA 19-9-related benign diseases, CT detected 34 benign diseases (48.6 %) providing an alternative diagnosis for elevated CA 19-9. CONCLUSION: Abdominopelvic CT is not only useful in detecting malignancies, but can also diagnose alternative benign causes of elevated CA 19-9 in asymptomatic screening tests. KEY POINTS: * Fifteen percent of asymptomatic patients with elevated CA19 9 may have intra-abdominal malignancies. * Mean value of CA19-9 is different among malignant, benign, and non-related groups. * CT shows excellent sensitivity for intra-abdominal malignancies as causatives of elevated CA19-9. * CT provides alternative benign diagnoses as causatives of elevated CA19-9. * Detection of causatives of elevated CA19-9 using CT alleviates concerns and uncertainty. PMID- 25113647 TI - Diffusion-weighted imaging for the detection of mesenteric small bowel tumours with Magnetic Resonance--enterography. AB - PURPOSE: To retrospectively investigate the added value of diffusion-weighted MR imaging (DWI) for detecting mesenteric small bowel tumours (MSBTs) via MR enterography. MATERIALS AND METHODS: MR-enterographies of 98 patients with suspected MSBTs were blindly analyzed by two independent readers for the presence of MSBTs. Four imaging sets including "standard" (Haste and TrueFisp), "standard + DWI," "standard + gadolinium-enhanced" and "standard + DWI + gadolinium enhanced" were reviewed. Diagnostic performance of different readings were compared with McNemar's test. RESULTS: Twenty-nine MSBTs were pathologically confirmed. For R1 (junior radiologist) sensitivity, specificity, PPV, NPV and accuracy for the detection of MSBTs via standard MRI were 52 % [95 % CI: 34 %-70 %] (15/29), 94 % [95 % CI: 89 %-100 %] (65/69), 79 % [95 % CI: 61 %-97 %] (15/19), 82 % [95 % CI: 74 %-91 %] (65/79) and 82 % [95 % CI: 74 %-89 %] (80/98), respectively. For R2 (senior radiologist) they were 76 % [95 % CI: 60 %-91 %] (22/29), 96 % [95 % CI: 91-100 %] (66/69), 88 % [95 % CI: 75 %-100 %] (22/25), 90 % [95 % CI: 84 %-97 %] (66/73) and 90 % [95 % CI: 84 %-96 %] (88/98), respectively. Adding DWI they were 72 % [95 % CI: 56 %-89 %] (21/29), 91 % [95 % CI: 85 %-98 %] (63/69), 78 % [95 % CI: 62 %-94 %] (21/27), 89 % [95 % CI: 81 %-96 %] (63/71) and 87 % [95 % CI: 80 %-94 %] (85/98) for R1 and 79 % [95 % CI: 65 % 94 %] (23/29), 97 % [95 % CI: 93 %-100 %] (67/69), 92 % [95 % CI: 81 %-100 %] (23/25), 92 % [95 % CI: 86 %-98 %] (67/73) and 92 % [95 % CI: 86 %-97 %] (90/98) for R2. Sensitivities for tumour detection were higher after adding DWI to standard MRI, although only for R1 was this significant (P = 0.03). Adding DWI to standard + gadolinium-enhanced MRI did not significantly increase MR performance. CONCLUSION: DWI improves MSBT detection via MR-enterography compared to standard unenhanced MR-enterography, especially for unexperienced readers. KEY POINTS: * MR-enterography is accurate for the detection of mesenteric small-bowel tumours. * Diffusion-weighted sequencing helps inexperienced readers detect small-bowel tumours with MR-enterography. * Diffusion-weighted sequencing adds value to standard MR-enterography when gadolinium is contraindicated. PMID- 25113648 TI - Diagnostic performance of shear wave elastography in the identification of malignant thyroid nodules: a meta-analysis. AB - OBJECTIVE: This meta-analysis aimed to assess the performance of shear wave elastography (SWE) in the identification of malignant thyroid nodules. METHODS: Web of Science, Scopus, PubMed, and the references of narrative reviews were searched for relevant studies with a publication date through October 2013. The methodological quality was assessed using QUADAS tools. Data synthesis was calculated using the bivariate mixed-effects regression model. RESULTS: Of the 131 studies identified, 15 (11.5 %) were included, in which SWE, point-SWE or 2D SWE, was used to evaluate 1,867 thyroid nodules in 1,525 patients. Methodological assessment revealed study quality was moderate to high. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve of SWE for detecting malignant thyroid nodules were 84.3 % (95 % confidence interval [CI], 76.9-89.7 %), 88.4 % (95 % CI, 84.0-91.7 %), and 93 % (95 % CI, 90 95 %), respectively. As a screening tool, positive and negative predictive values were 27.7-44.7 % and 98.1-99.1 %, respectively, calculated with a malignance prevalence of 5-10 % in thyroid nodules. A publication bias regression test revealed no significant small-study bias. CONCLUSIONS: SWE is a highly accurate diagnostic modality for the identification of malignant thyroid nodules, with promise for integration into routine imaging protocols for thyroid nodules. KEY POINTS: * Shear wave elastography (SWE) is a group of novel ultrasound-based technologies. * Meta-analysis was employed to assess relevant studies of SWE of thyroid nodules. * SWE had high sensitivity and specificity in identifying malignant thyroid nodules. * The high negative predictive value of SWE can reduce unnecessary biopsies. PMID- 25113649 TI - Quantitative assessment of right ventricular function and pulmonary regurgitation in surgically repaired tetralogy of Fallot using 256-slice CT: comparison with 3 Tesla MRI. AB - OBJECTIVES: To compare 256-slice cardiac computed tomography (CCT) with cardiac magnetic resonance (CMR) imaging to assess right ventricular (RV) function and pulmonary regurgitant fraction (PRF) in patients with repaired tetralogy of Fallot (TOF). METHODS: Thirty-three consecutive patients with repaired TOF underwent retrospective ECG-gated CCT and 3-Tesla CMR. RV and left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) were measured using CCT and CMR. PRF-CCT (%) was defined as (RVSV - LVSV)/RVSV. PRF-CMR (%) was measured by the phase-contrast method. Repeated measurements were performed to determine intra- and interobserver variability. RESULTS: CCT measurements, including PRF, correlated highly with the CMR reference (r = 0.71-0.96). CCT overestimated RVEDV (mean difference, 17.1 +/- 2.9 ml), RVESV (12.9 +/- 2.1 ml) and RVSV (4.2 +/- 2.0 ml), and underestimated RVEF (-2.6 +/- 1.0%) and PRF (-9.1 +/- 2.0%) compared with CMR. The limits of agreement between CCT and CMR were in a good range for all measurements. The variability in CCT measurements was lower than those in CMR. The estimated effective radiation dose was 7.6 +/- 2.6 mSv. CONCLUSIONS: 256 slice CCT can assess RV function and PRF with relatively low dose radiation exposure in patients with repaired TOF, but overestimates RV volume and underestimates PRF. KEY POINTS: 256-slice CT assessment of RV function is highly reproducible in repaired TOF. Pulmonary regurgitation can be evaluated by biventricular systolic volume difference. CT overestimates RV volume and underestimates pulmonary regurgitation, compared with MRI. PMID- 25113650 TI - A new technique for noise reduction at coronary CT angiography with multi-phase data-averaging and non-rigid image registration. AB - OBJECTIVES: To investigate the feasibility of a newly developed noise reduction technique at coronary CT angiography (CTA) that uses multi-phase data-averaging and non-rigid image registration. METHODS: Sixty-five patients underwent coronary CTA with prospective ECG-triggering. The range of the phase window was set at 70 80% of the R-R interval. First, three sets of consecutive volume data at 70%, 75% and 80% of the R-R interval were prepared. Second, we applied non-rigid registration to align the 70% and 80% images to the 75% image. Finally, we performed weighted averaging of the three images and generated a de-noised image. The image noise and contrast-to-noise ratio (CNR) in the proximal coronary arteries between the conventional 75% and the de-noised images were compared. Two radiologists evaluated the image quality using a 5-point scale (1, poor; 5, excellent). RESULTS: On de-noised images, mean image noise was significantly lower than on conventional 75% images (18.3 HU +/- 2.6 vs. 23.0 HU +/- 3.3, P < 0.01) and the CNR was significantly higher (P < 0.01). The mean image quality score for conventional 75% and de-noised images was 3.9 and 4.4, respectively (P < 0.01). CONCLUSIONS: Our method reduces image noise and improves image quality at coronary CTA. KEY POINTS: * We introduce a new method for image noise reduction at cardiac CT. * Multiple data acquisitions of an object and their averaging yield lower noise. * Our method uses multi-phase images reconstructed from unused redundant imaging data. * It reduces image noise by averaging multi phase images transformed by non-rigid registration. * This method achieves a 20% image noise reduction at cardiac CT. PMID- 25113651 TI - Ethical issues for late-stage trials of multipurpose prevention technologies for HIV and pregnancy. AB - Multipurpose prevention technologies (MPTs) designed to simultaneously prevent pregnancy and HIV could provide urgently needed tools to address unmet sexual and reproductive health needs of women worldwide. Late-stage clinical trials will be complex given the need to demonstrate efficacy for HIV and contraceptive indications simultaneously from a single product. Currently, HIV and pregnancy prevention trials have distinctive design features that will need to be reconciled in MPT trials. This article identifies several ethical issues uniquely associated with this research that will benefit from future deliberation and guidance to ensure that this globally important research can proceed efficiently and expeditiously. PMID- 25113652 TI - Prediction of domestic violence against married women in southwestern Turkey. AB - OBJECTIVE: To determine the prevalence of, and independent risk factors for various domestic violence categories among married women of reproductive age in southwestern Turkey. METHODS: The present cross-sectional study included 260 randomly selected women registered to a family physician in the district of Gonen, Isparta. During home visits between October 1 and December 31, 2012, the women completed a questionnaire that included between four and eight questions for each violence category (physical, verbal, economic, emotional, and sexual) to assess the lifetime presence of domestic violence. Logistic regression models with backward elimination were constructed to define independent risk factors for domestic violence. RESULTS: In total, 176 (67.7%) women reported any type of domestic violence at least once in their lifetime. Verbal/psychological abuse was the most frequent type (reported by 121 [46.5%] women). Living in a village, young age (19-29 years) of the husband, adolescent age (<19 years) of the husband at marriage, and problem alcohol use or problem gambling in the partner were independent predictors of domestic violence. CONCLUSION: Attention should be given to area of residence, age of both partners at marriage, adolescent marriage, and husband characteristics during screening for domestic violence. PMID- 25113653 TI - Relationship between serum gamma-glutamyltransferase levels and prehypertension in Chinese adults: the cardiometabolic risk in Chinese study. AB - The authors aimed to investigate the relationship between serum gamma glutamyltransferase (GGT) and prehypertension, as well as the modification of other metabolic risk factors in a large cohort of Chinese individuals. The data were collected via a community-based health examination survey in central China. Blood pressure, body mass index (BMI), and levels of GGT, fasting blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid indicators were measured. In total, data from 18,302 patients with available biomarkers were included in the present study. Elevated blood pressure was associated with increased GGT concentration (P<.001). After adjusting for age, sex, BMI, fasting blood glucose, lipid indicators, AST, and family history of hypertension, the association between GGT levels and prehypertension remained significant (P=.021). The adjusted odds ratios (95% confidence interval) for prehypertension across quintiles of GGT level were 1.00, 1.057 (1.012-1.334), 1.068 (0.916-1.254), 1.024 (0.851-1.368), and 1.272 (1.027-1.593), respectively. In stratified analyses, the association between GGT levels and prehypertension was significant in women but was not significant in men. Moreover, additive effect of BMI and age on the effect of GGT levels on prehypertension (both P for interaction <.001) was observed. In summary, GGT levels were positively associated with prehypertension in women, independent of other metabolic factors. Furthermore, BMI and age may amplify the effects of GGT levels on prehypertension. These findings suggest that monitoring the levels of GGT could help in the diagnosis and monitoring of prehypertension. PMID- 25113657 TI - A brief history of cancer: age-old milestones underlying our current knowledge database. AB - This mini-review chronicles the history of cancer ranging from cancerous growths discovered in dinosaur fossils, suggestions of cancer in Ancient Egyptian papyri written in 1500-1600 BC, and the first documented case of human cancer 2,700 years ago, to contributions by pioneers beginning with Hippocrates and ending with the originators of radiation and medical oncology. Fanciful notions that soon fell into oblivion are mentioned such as Paracelsus and van Helmont substituting Galen's black bile by mysterious ens or archeus systems. Likewise, unfortunate episodes such as Virchow claiming Remak's hypotheses as his own remind us that human shortcomings can affect otherwise excellent scientists. However, age-old benchmark observations, hypotheses, and practices of historic and scientific interest are underscored, excerpts included, as precursors of recent discoveries that shaped modern medicine. Examples include: Petit's total mastectomy with excision of axillary glands for breast cancer; a now routine practice, Peyrilhe's ichorous matter a cancer-causing factor he tested for transmissibility one century before Rous confirmed the virus-cancer link, Hill's warning of the dangers of tobacco snuff; heralding today's cancer pandemic caused by smoking, Pott reporting scrotum cancer in chimney sweepers; the first proven occupational cancer, Velpeau's remarkable foresight that a yet unknown subcellular element would have to be discovered in order to define the nature of cancer; a view confirmed by cancer genetics two centuries later, ending with Rontgen and the Curies, and Gilman et al. ushering radiation (1896, 1919) and medical oncology (1942), respectively. PMID- 25113654 TI - Ultrasound imaging of the trapeziometacarpal articular cavity to investigate the presence of intraarticular gas bubbles after chiropractic manipulation. AB - OBJECTIVE: The purpose of this study was to investigate the presence of intraarticular gas bubbles in the trapeziometacarpal joint cavity after chiropractic manipulation with audible cavitation and to assess the state of the gas bubbles after a 20-minute refractory period. METHODS: This investigation included 18 asymptomatic male and female participants between the ages of 21 and 26 years. High-resolution (15 MHz) sonograms of the trapeziometacarpal articular cavity were obtained by an experienced musculoskeletal ultrasonographer at 3 intervals: premanipulation, within 30 seconds postmanipulation, and at 20 minutes postmanipulation. The sonograms were saved as digital copies for subsequent reports that were correlated with reports compiled during dynamic visualization of the articular cavity. Data were extracted from the reports for analysis. RESULTS: The premanipulative sonograms showed that 27.78% of joints contained minute gas bubbles, also known as microcavities, within the synovial fluid before the joint was manipulated. The remaining 72.22% of joints contained no intraarticular microcavities. All of the postmanipulative sonograms revealed numerous large conspicuous gas bubbles within the synovial fluid. The postrefractory sonograms showed that, in 66.66% of the synovial fluid, gas bubbles were still visible, whereas the remaining 33.34% had no presence of gas bubbles or microcavities, and the synovial fluid had returned to its premanipulative state. CONCLUSION: The findings of this study suggest that synovial fluid may contain intraarticular microcavities even before a manipulation is performed. Numerous large intraarticular gas bubbles are formed during manipulation due to cavitation of the synovial fluid and were observed in the absence of an axial distractive load at the time of imaging. In most cases, these gas bubbles remained within the joint for longer than 20 minutes. PMID- 25113655 TI - Paediatric hereditary angioedema: a survey of UK service provision and patient experience. AB - Hereditary angioedema (HAE) is a rare disease characterized by episodes of potentially life-threatening angioedema. For affected children in the United Kingdom, there are relatively few data regarding disease prevalence, service organization and the humanistic burden of the disease. To improve knowledge in these areas, we surveyed major providers of care for children with HAE. A questionnaire was sent to major paediatric centres to determine patient numbers, symptoms, diagnostic difficulties, management and available services. In addition, all patients at a single centre were given a questionnaire to determine the experiences of children and their families. Sixteen of 28 centres responded, caring for a total of 111 UK children. Seven children had experienced life threatening crises. One-third of patients were on long-term prophylactic medication, including C1 inhibitor prophylaxis in four children. Eight centres reported patients who were initially misdiagnosed. Broad differences in management were noted, particularly regarding indications for long-term prophylaxis and treatment monitoring. We also noted substantial variation in the organization of services between centres, including the number of consultants contributing to patient care, the availability of specialist nurses, the availability of home therapy training and the provision of patient information. Ten of 12 patient/carer questionnaires were returned, identifying three common themes: the need to access specialist knowledge, the importance of home therapy and concerns around the direct effect of angioedema on their life. To our knowledge, this study represents the first dedicated survey of paediatric HAE services in the United Kingdom and provides useful information to inform the optimization of services. PMID- 25113658 TI - Phase II drugs currently being investigated for the treatment of hypogonadism. AB - INTRODUCTION: Hypogonadism is the most common endocrine disorder, which affects men of all age groups. Recent shifts in public awareness, increased screening and recognition of symptoms and updated diagnostic criteria have led to an increase in men diagnosed as hypogonadal, including middle-aged and older men who previously would have been considered eugonadal. The increase in testosterone replacement therapy (TRT) has paralleled an increase in advancements of treatment options. Although current therapies are highly efficacious for many men, there remains a need for newer therapies that are more cost-effective, preserve ease of use and administration, mitigate undesirable effects and closely mimic physiological levels of testosterone. AREAS COVERED: In this review, the authors discuss current TRTs and therapies in development for the treatment of hypogonadism. The focus is on therapies under Phase II investigation or those who have recently completed Phase II study. EXPERT OPINION: With several new therapies in development, the authors expect advancements in achieving treatment benchmarks that meet the needs of the individual symptomatic hypogonadal male. Increased public awareness of hypogonadism and TRT has led to a welcomed expansion in the choice of TRT options. These include new delivery systems, formulations, routes of administration and non-testosterone modalities. PMID- 25113659 TI - A simple and sensitive fluorescence based biosensor for the determination of uric acid using H2O2-sensitive quantum dots/dual enzymes. AB - A novel optical detection system consisting of combination of uricase/HRP-CdS quantum dots (QDs) for the determination of uric acid in urine sample is described. The QDs was used as an indicator to reveal fluorescence property of the system resulting from enzymatic reaction of uricase and HRP (horseradish peroxidase), which is involved in oxidizing uric acid to allaintoin and hydrogen peroxide. The hydrogen peroxide produced was able to quench the QDs fluorescence, which was proportional to uric acid concentration. The system demonstrated sufficient activity of uricase and HRP at a ratio of 5U:5U and pH 7.0. The linearity of the system toward uric acid was in the concentration range of 125 1000 uM with detection limit of 125 uM. PMID- 25113660 TI - Examining the link between adolescent brain development and risk taking from a social-developmental perspective (reprinted). AB - The adolescent age period is often characterized as a health paradox because it is a time of extensive increases in physical and mental capabilities, yet overall mortality/morbidity rates increase significantly from childhood to adolescence, often due to preventable causes such as risk taking. Asynchrony in developmental time courses between the affective/approach and cognitive control brain systems, as well as the ongoing maturation of neural connectivity are thought to lead to increased vulnerability for risk taking in adolescence. A critical analysis of the frequency of risk taking behaviors, as well as mortality and morbidity rates across the lifespan, however, challenges the hypothesis that the peak of risk taking occurs in middle adolescence when the asynchrony between the different developmental time courses of the affective/approach and cognitive control systems is the largest. In fact, the highest levels of risk taking behaviors, such as alcohol and drug use, often occur among emerging adults (e.g., university/college students), and highlight the role of the social context in predicting risk taking behavior. Moreover, risk taking is not always unregulated or impulsive. Future research should broaden the scope of risk taking to include risks that are relevant to older adults, such as risky financial investing, gambling, and marital infidelity. In addition, a lifespan perspective, with a focus on how associations between neural systems and behavior are moderated by context and trait-level characteristics, and which includes diverse samples (e.g., divorced individuals), will help to address some important limitations in the adolescent brain development and risk taking literature. PMID- 25113662 TI - Mechanochemical preparation of nanocrystalline BaFCl doped with samarium in the 2+ oxidation state. AB - We report a facile mechanochemical preparation method for nanocrystalline BaFCl doped with samarium in the 2+ oxidation state by ball milling BaCl2, BaF2, and SmI2 under a nitrogen atmosphere. The resulting phosphors were characterized by powder X-ray diffraction; electron microscopy, X-ray photoelectron spectroscopy; and photoluminescence, photoexcitation, cathodoluminescence, and diffuse reflectance spectroscopy. This is the first report of a direct preparation method of Sm(2+) doped alkaline earth fluorohalides at room temperature and points to a significant potential for the preparation of a wide range of related X-ray storage phosphors containing rare earth ions in divalent and trivalent cationic states by mechanochemical methods. PMID- 25113661 TI - Laparoscopic repair of posttraumatic diaphragmatic rupture. Report of three cases. AB - INTRODUCTION: Posttraumatic diaphragmatic rupture (PTDR) is a rare complication of thoracoabdominal injuries. In the emergency phase, it is generally treated via wide laparotomy. The laparoscopic approach is controversial and it is reserved for the chronic type of PTDR. Herein we present three cases of laparoscopic treatment of PTDR, one of which was conducted early after the injury. PRESENTATION OF CASE: The patients' age was 42, 66 and 53 years and the time from the injury until the operation 1 week, 2 months and 4 years, respectively. Hernia involved the left hemidiaphragm in two patients and the right hemidiaphragm in the second patient. Prolapsing viscera were the omentum/stomach/spleen, the small intestine and the omentum/large bowel, respectively. The PTDR was diagnosed right after the injury of the first patient but its treatment was postponed until the fourth day of hospitalization because of severe respiratory distress due to bilateral pneumothorax, flail chest and extended bilateral lung contusions. All patients underwent laparoscopic operation and correction of the hernia with the use of non-absorbable sutures or endoclips in two patients. There were no serious intra- or postoperative complications and the patients were discharged 30, 5, 6 days after the operation. After a period of 1, 8 and 9 years, respectively the patients remain without clinical evidence of recurrence. DISCUSSION: Trauma is the major cause of acquired diaphragmatic hernias. CONCLUSION: Laparoscopy is an attractive approach for the management of chronic PTDR. Moreover, it may offer the benefits of minimally invasive surgery during the acute phase of injury in highly selected patients. PMID- 25113663 TI - Relighting behaviour among cigarette smokers seeking treatment: implications for tobacco treatment and policy. AB - AIMS: During the recent economic downturn, trends towards fewer cigarettes smoked per day have emerged along with the practice of extinguishing and relighting cigarettes. Few studies have characterised factors related to relighting cigarettes and none have explored this behaviour in those seeking tobacco treatment. This study describes treatment-seeking patients who relight cigarettes and examines implications on tobacco policy and treatment. METHODS: Data were collected from a cross-sectional sample of 496 patients at a specialty tobacco treatment programme in New Jersey from 2010 to 2012. RESULTS: Forty-six per cent of the sample reported relighting, and those subjects smoked significantly fewer cigarettes per day (CPD), despite similar levels of dependence and exhaled carbon monoxide (CO) values. In unadjusted analyses, significantly higher rates of relighting were found among females, African-Americans, smokers who had a high school diploma or less, and were unemployed, sick or disabled. Relighting was more prevalent among smokers with higher markers of dependence, menthol smoking and night smoking. In multivariate analyses, markers of dependence and economic factors (employment and education) remained significant. CONCLUSIONS: Characteristics linked to economic factors were related to increased relighting. Implications for tobacco treatment include the impact on pharmacotherapy dosing and counselling interventions. The tobacco control community needs to be aware of this phenomenon. Collecting data on 'smoking sessions per day' might be a more accurate depiction of smoking exposure than CPD. PMID- 25113664 TI - Time to analgesia for care delivered by nurse practitioners in the emergency department - a retrospective chart audit. AB - OBJECTIVES: To evaluate quality of care delivered to patients presenting to the emergency department (ED) with pain and managed by emergency nurse practitioners by: 1 Evaluating time to analgesia from initial presentation 2 Evaluating time from being seen to next analgesia 3 Measuring pain score documentation BACKGROUND: The delivery of quality care in the emergency department (ED) is emerging as one of the most important service indicators being measured by health services. Emergency nurse practitioner services are designed to improve timely, quality care for patients. One of the goals of quality emergency care is the timely and effective delivery of analgesia for patients. Timely analgesia is an important indicator of ED service performance. METHODS: A retrospective explicit chart review of 128 consecutive patients with pain and managed by emergency nurse practitioners was conducted. Data collected included demographics, presenting complaint, pain scores, and time to first dose of analgesia. Patients were identified from the ED patient information system (Cerner log) and data were extracted from electronic medical records. RESULTS: Pain scores were documented in 67 (52.3%; 95% CI: 43.3-61.2) patients. The median time to analgesia from presentation was 60.5 (IQR 30-87) minutes, with 34 (26.6%; 95% CI: 19.1-35.1) patients receiving analgesia within 30 minutes of presentation to hospital. There were 22 (17.2%; 95% CI: 11.1-24.9) patients who received analgesia prior to assessment by a nurse practitioner. Among patients who received analgesia after assessment by a nurse practitioner, the median time to analgesia after assessment was 25 (IQR 12-50) minutes, with 65 (61.3%; 95% CI: 51.4-70.6) patients receiving analgesia within 30 minutes of assessment. CONCLUSIONS: The majority of patients assessed by nurse practitioners received analgesia within 30 minutes after assessment. However, opportunities for substantial improvement in such times along with documentation of pain scores were identified and will be targeted in future research. PMID- 25113665 TI - A new method for modeling coalescent processes with recombination. AB - BACKGROUND: Recombination plays an important role in the maintenance of genetic diversity in many types of organisms, especially diploid eukaryotes. Recombination can be studied and used to map diseases. However, recombination adds a great deal of complexity to the genetic information. This renders estimation of evolutionary parameters more difficult. After the coalescent process was formulated, models capable of describing recombination using graphs, such as ancestral recombination graphs (ARG) were also developed. There are two typical models based on which to simulate ARG: back-in-time model such as ms and spatial model including Wiuf&Hein's, SMC, SMC', and MaCS. RESULTS: In this study, a new method of modeling coalescence with recombination, Spatial Coalescent simulator (SC), was developed, which considerably improved the algorithm described by Wiuf and Hein. The present algorithm constructs ARG spatially along the sequence, but it does not produce any redundant branches which are inevitable in Wiuf and Hein's algorithm. Interestingly, the distribution of ARG generated by the present new algorithm is identical to that generated by a typical back-in time model adopted by ms, an algorithm commonly used to model coalescence. It is here demonstrated that the existing approximate methods such as the sequentially Markov coalescent (SMC), a related method called SMC', and Markovian coalescent simulator (MaCS) can be viewed as special cases of the present method. Using simulation analysis, the time to the most common ancestor (TMRCA) in the local trees of ARGs generated by the present algorithm was found to be closer to that produced by ms than time produced by MaCS. Sample-consistent ARGs can be generated using the present method. This may significantly reduce the computational burden. CONCLUSION: In summary, the present method and algorithm may facilitate the estimation and description of recombination in population genomics and evolutionary biology. PMID- 25113666 TI - The palmar approach for PIP-arthroplasty according to Simmen: results after 8 years follow-up. AB - BACKGROUND: Alloarthroplasty of the proximal interphalangeal joint is indicated for patients with osteoarthritis, an inflammatory disease of the joint. According to the current literature, implants made of silicone are not inferior to newer implants and the complications are well known. Therefore, focus should be shifted to the operative approach to improve the results. METHODS: Eleven silicone arthroplasties in 7 patients with arthritis and 35 silicone arthroplasties in 23 patients with osteoarthritis were reviewed after 15.6 months and after 105.3 months. All implants were inserted using the palmar approach according to Simmen. We compared the pre- and postoperative arc of motion, pain, and strength, and present postoperative complications and satisfaction. RESULTS: Patients with arthritis showed a gain in range of motion of 36 degrees and patients with osteoarthritis of 39 degrees . No implant failure occurred, and one revision was performed,. Average extension lag over all operated joints of patients was 2.8 degrees . No swan-neck deformity or extensor tendon adhesion was observed. There was no significant difference in the postoperative results between patients with osteoarthritis and arthritis or between first and second follow-up. CONCLUSION: Silicone arthroplasty restores the functionality of proximal interphalangeal joints in patients with osteoarthritis and inflammatory joint disease. Using a palmar approach, the surgeon can reach palmar and dorsal osteophytes. The extensor mechanism stays intact reducing the risk for extensor lag and other complications compared to the dorsal approach. The results do not change significantly between 1 and 8 years postoperatively. PMID- 25113667 TI - Bone substitute first or screws first? A biomechanical comparison of two operative techniques for tibial-head depression fractures. AB - BACKGROUND: The aim of this study was to investigate a drillable and injectable bone substitute (calcium phosphate cement) and the operative technique enabled by the drillable option in a new biomechanical fracture model for tibial depression fractures in synthetic bones. MATERIALS AND METHODS: Lateral depression fractures of the tibial plateau (AO 41-B2, Schatzker III) were created in a biomechanical fracture model in three different synthetic bones (Sawbone 3401, Synbone 1110/1116). Reproducible fractures were generated employing Synbone 1110, which exhibited a comparable strength to human osteoporotic bones and was used for the further experiments. After reduction of the fractures, the stabilization was performed with two different operative techniques. In group 1, first an osteosynthesis with four screws was performed and then the metaphyseal defect was filled up with calcium phosphate cement (Norian drillable). In group 2, initially the filling up with Norian drillable was done enabling a complete filling of the defect, followed by placing of the screws. Displacement under cyclic loading with 250 N for 3,000 cycles, stiffness, and maximum load in load-to-failure tests were determined. RESULTS: A comparison of the two operative techniques of stabilization showed a distinctly lower displacement and higher stiffness for group 2 when the defect was filled up first. For the maximum load, no significant differences could be demonstrated. CONCLUSIONS: A complete filling of the defect by first applying the calcium phosphate cement significantly reduces the secondary loss of reduction of the depression fracture fragment under cyclic loading with a clinically relevant partial weight bearing. The beneficial effects of drillable calcium phosphate cement may also be transferable to defects other than tibial-head depression fractures. PMID- 25113669 TI - Alkene carboboration enabled by synergistic catalysis. AB - A synergistic Pd/Cu system for the coupling of alkenes, (Bpin)2 (pin = pinacolate), and aryl/vinyl bromides is disclosed. This method allows for the catalytic generation of secondary Csp(3)-Cu nucleophiles in situ and subsequent Pd-catalyzed cross-coupling. PMID- 25113668 TI - Metabotropic glutamate receptor 1 recycles to the cell surface in protein phosphatase 2A-dependent manner in non-neuronal and neuronal cell lines. AB - Trafficking of G protein-coupled receptors plays a crucial role in controlling the precise signalling of the receptor as well as its proper regulation. Metabotropic glutamate receptor 1 (mGluR1), a G protein-coupled receptor, is a member of the group I mGluR family. mGluR1 plays a critical role in neuronal circuit formation and also in multiple types of synaptic plasticity. This receptor has also been reported to be involved in various neuropsychiatric diseases. Other than the central nervous system, mGluR1 plays crucial roles in various non-neuronal cells like hepatocytes, skin cells, etc. Although it has been reported that mGluR1 gets endocytosed on ligand application, the events after the internalization of the receptor has not been studied. We show here that mGluR1 internalizes on ligand application. Subsequent to endocytosis, majority of the receptors localize at the recycling compartment and no significant presence of the receptor was noticed in the lysosome. Furthermore, mGluR1 returned to the cell membrane subsequent to ligand-mediated internalization. We also show here that the recycling of mGluR1 is dependent on the activity of protein phosphatase 2A. Thus, our data suggest that the ligand-mediated internalized receptors recycle back to the cell surface in protein phosphatase 2A-dependent manner. PMID- 25113671 TI - Investigation of phase diagrams and physical stability of drug-polymer solid dispersions. AB - Solid dispersion technology has been widely explored to improve the solubility and bioavailability of poorly water-soluble compounds. One of the critical drawbacks associated with this technology is the lack of physical stability, i.e. the solid dispersion would undergo recrystallization or phase separation thus limiting a product's shelf life. In the current study, the melting point depression method was utilized to construct a complete phase diagram for felodipine (FEL)-Soluplus(r) (SOL) and ketoconazole (KTZ)-Soluplus(r) (SOL) binary systems, respectively, based on the Flory-Huggins theory. The miscibility or solubility of the two compounds in SOL was also determined. The Flory-Huggins interaction parameter chi values of both systems were calculated as positive at room temperature (25 degrees C), indicating either compound was miscible with SOL. In addition, the glass transition temperatures of both solid dispersion systems were theoretically predicted using three empirical equations and compared with the practical values. Furthermore, the FEL-SOL solid dispersions were subjected to accelerated stability studies for up to 3 months. PMID- 25113672 TI - Complete genome sequence analysis of goatpox virus isolated from China shows high variation. AB - Goatpox virus (GTPV), a member of the Capripoxvirus genus of the Poxviridae family, is the causative agent of variolo caprina (goatpox). GTPV can cause significant economic losses of domestic ruminants in endemic regions and can threaten breeding stocks. In this study, we report on the compilation of the complete genomic sequence of an isolated GTPV field strain FZ (GTPV_FZ). The 150,194bp GTPV genome consists of a central coding region bounded by two identical 2301bp inverted terminal repeats and contains 151 putative genes. Comparative genomic analysis reveals the apparent genetic relationships among Capripoxviruses are close, but sufficient genomic variants in the field isolate strain FZ have been identified to distinguish it from other GTPV strains and other Capripoxvirus species. Phylogenetic analysis based on the p32 and complete GTPV genome can be used to differentiate SPPVs, GTPVs and LSDVs. These data may contribute to the epidemiological study of the Chinese capripoxvirus and help to develop more specific detection methods to distinguish GTPVs, SPPVs and LSDVs. PMID- 25113670 TI - Intrathecal delivery of mesenchymal stromal cells protects the structure of altered perineuronal nets in SOD1 rats and amends the course of ALS. AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder resulting in a lethal outcome. We studied changes in ventral horn perineuronal nets (PNNs) of superoxide dismutase 1 (SOD1) rats during the normal disease course and after the intrathecal application (5 * 10(5) cells) of human bone marrow mesenchymal stromal cells (MSCs) postsymptom manifestation. We found that MSCs ameliorated disease progression, significantly improved motor activity, and prolonged survival. For the first time, we report that SOD1 rats have an abnormal disorganized PNN structure around the spinal motoneurons and give different expression profiles of chondroitin sulfate proteoglycans (CSPGs), such as versican, aggrecan, and phosphacan, but not link protein-1. Additionally, SOD1 rats had different profiles for CSPG gene expression (Versican, Hapln1, Neurocan, and Tenascin-R), whereas Aggrecan and Brevican profiles remained unchanged. The application of MSCs preserved PNN structure, accompanied by better survival of motorneurons. We measured the concentration of cytokines (IL-1alpha, MCP-1, TNF alpha, GM-CSF, IL-4, and IFN-gamma) in the rats' cerebrospinal fluid and found significantly higher concentrations of IL-1alpha and MCP-1. Our results show that PNN and cytokine homeostasis are altered in the SOD1 rat model of ALS. These changes could potentially serve as biological markers for the diagnosis, assessment of treatment efficacy, and prognosis of ALS. We also show that the administration of human MSCs is a safe procedure that delays the loss of motor function and increases the overall survival of symptomatic ALS animals, by remodeling the recipients' pattern of gene expression and having neuroprotective and immunomodulatory effects. PMID- 25113674 TI - Six new species, complementary descriptions and new records from the Neotropical Region of the spider genus Dipoena (Araneae: Theridiidae). AB - The theridiid genus Dipoena Thorell, 1869 is distributed worldwide. Dipoena are recognized by male with carapace often high, cylindrical, with grooves or depression on dorsum; carapace of female rarely modified, sometimes high. In this paper six new species of Dipoena are described from Brazil, one from the state of Mato Grosso do Sul: Dipoena bonitensis new species, three from Sao Paulo: Dipoena cidae new species, Dipoena ericae new species and Dipoena santaritadopassaquatrensis new species and two from Parana: Dipoena guaraquecaba new species and Dipoena fozdoiguacuensis new species, all based on males and females. The males of Dipoena pusilla (Keyserling, 1886); D. peruensis Levi, 1963; D. olivenca Levi, 1963 and D. esra Levi, 1963 and the female of Dipoena niteroi Levi, 1963 are here described and illustrated for the first time. New records from Brazil include Dipoena augara Levi, 1963; D. bryantae Chickering, 1943; D. duodecimpunctata Chickering, 1943; D. isthmia Chickering, 1943; D. kuyuwini Levi, 1963; D. mendoza Levi, 1967; D. puertoricensis Levi, 1963; D. tiro Levi, 1963 and D. trinidensis Levi, 1963; and new records from Bolivia include Dipoena atlantica Chickering, 1943, D. cornuta Chickering, 1943 and D. kuyuwini. New distribution records within Brazil are presented for Dipoena cordiformis Keyserling, 1886; D. hortoni Chickering, 1943; D. ira Levi, 1963; D. militaris Chickering, 1943; D. obscura Keyserling, 1891; D. pumicata (Keyserling, 1886); D. santacatarinae Levi, 1963; D. tingo Levi, 1963 and D. variabilis (Keyserling, 1886). PMID- 25113673 TI - Pheno- and genotyping of Brucella abortus biovar 5 isolated from a water buffalo (Bubalus bubalis) fetus: First case reported in the Americas. AB - An isolate of Brucella spp. from an aborted water buffalo (Bubalus bubalis) fetus was characterized based on its pheno- and genotype. The phenotype was defined by carbon dioxide requirement, hydrogen sulfide production, sensitivity to thionin and basic fuchsin and agglutination with Brucella A and M monospecific antisera. The genotype was based on the amplification of the following genes: bcsp31, omp2ab, and eri and the species-specific localization of the insertion sequence IS711 in the Brucella chromosome via B. abortus-B. melitensis-B. ovis-B. suis (AMOS)-PCR. Unexpectedly, the isolate showed a phenotype different from B. abortus bv 1, the most prevalent strain in cattle in Argentina, and from vaccine strain 19, currently used in bovines and water buffaloes. Genotyping supported the phenotypic results, as the analysis of the omp2ab gene sequence showed an identical pattern to either B. abortus bv 5 or B. melitensis. Finally, the AMOS PCR generated a 1700-bp fragment from the isolate, different than those amplified from B. abortus bv 1 (498bp) and B. melitensis (731bp), confirming the presence of B. abortus bv 5. The OIE/FAO Reference Laboratory for Brucellosis confirmed this typing. This is the first report of B. abortus bv 5 from a water buffalo in the Americas. PMID- 25113675 TI - A taxonomic revision of South African Sharphydrus, with the description of two new species (Coleoptera: Dytiscidae: Bidessini). AB - Sharphydrus Omer-Cooper, 1958 is one of two endemic bidessine genera currently recognised from South Africa. Here Sharphydrus brincki sp. nov. and Sharphydrus kamiesbergensis sp. nov. are described from the Cederberg and Gydopas areas of the Western Cape, and the high Kamiesberg of the Northern Cape respectively, doubling the known species of this genus. It is shown that S. brincki sp. nov. has been included under S. capensis (Omer-Cooper, 1955) in the past, but that these are quite distinct taxa, differing in the extent of their elytral keels and male genitalia. Sharphydrus species are inhabitants of pools in seasonally fluctuating rivers, the new species described here occurring in areas which are somewhat transitional between fynbos and karoo biomes. An updated key is presented to Sharphydrus species, together with data on the distribution and ecology of known species, and a discussion of the status of the genus within the Bidessini. PMID- 25113676 TI - Psorodonotus venosus group (Orthoptera, Tettigoniidae; Tettigoniinae): geometric morphometry revealed two new species in the group. AB - Psorodonotus (Orthoptera, Tettigoniidae) includes 11 species distributed in Caucasus, Anatolia and Balkans. Although its present taxonomy is problematic, mainly three species groups can be distinguished; (i) The Specularis Group, (ii) The Caucasicus Group and (iii) The Venosus Group. Our recent studies on the genus have revealed presence of two new species in the last species group. Morphology of the species group studied both qualitatively and quantitatively using linear metric data of pronotum, tegmina and hind femur, and geometric data of male cerci and ovipositor. Morphological data were accompanied by data obtained from male calling song. Morphological and song data were produced from six different populations from North and Eastern part of Turkey: (1) Hakkari, (2) Tendurek, (3) Giresun, (4) Artvin, (5) Kars and (6) Agri. Qualitative and quantitative morphology, either linear-metric or geometric, suggest last three population as members of the same unit, but each of other three as different units. Song data are also largely in support of the morphological results. Necessary illustrations were provided to document results visually. Following conclusions were made: (1) the Artvin, Kars and Agri populations represent typical P. venosus and the Giresun population P. rugulosus, (2) each of the Hakkari and Tendurek populations represents a new species and P. hakkari sp. n. and P. tendurek sp. n. described by comparing with other members of P. venosus group, (3) P. rugulosus, P. hakkari sp. n. and P. tendurek sp. n. differ from P. venosus mainly by the longer cerci (extend to or beyond end of abdomen) and indistinct tubercles on surface of pronotal disc in female. P. rugulosus and P. tendurek sp. n. are also similar by sharing presence of two loud elements in a syllable (one in P. venosus, song of P. hakkari sp. n. is not available). But, similarities in phenotype are in conflict with relationships suggested by genetic data. PMID- 25113677 TI - Revision of the genus Alkindus Distant (Hemiptera: Heteroptera: Thyreocoridae: Corimelaeninae). AB - The neotropical genus Alkindus Distant is revised based on morphological characters (general morphology, including the external scent efferent system and leg structures, and external genital morphology). The male of Alkindus crassicosta Horvath is here described for the first time. Illustrations, an adapted key to species, and a compiled list of plants associated with both species are provided. Distribution records are expanded to include Guatemala and Brazil (Roraima) for Alkindus atratus Distant and Brazil (Santa Catarina) for A. crassicosta. PMID- 25113678 TI - Two new species of Gaeolaelaps (Acari: Laelapidae) from Iran. AB - This paper reports on two new species of mites of the genus Gaeolaelaps in soil from Iran, G. farajii sp. nov., and G. orbiculatus sp. nov.. A key to the species of Gaeolaelaps with short peritremes is presented. PMID- 25113679 TI - The red-listed species Thamnurgus rossicus in East Europe is a synonym of the rare Central European species, T. petzi (Curculionidae: Scolytinae). AB - The taxonomic status of Thamnurgus rossicus was evaluated with respect to the morphologically similar T. petzi using genetic markers. Nucleotide data from the mitochondrial COI gene revealed 2.4% variation between the European Alps and Russian steppe populations. The two nuclear DNA markers CAD and EF1a were identical across populations. In view of their similar morphology, genetic composition, and the partial overlap in host plant preferences (Ranunculaceae: Aconitum and Delphinium), T. rossicus is placed in synonymy with T. petzi. PMID- 25113680 TI - A new species of the genus Thoracochirus Bernhauer (Coleoptera: Staphylinidae: Osoriinae) from Yunnan, China. AB - Thoracochirus yunxianius sp. nov. is described from Yunnan, China. Color images of the habitus and aedeagus of the new species are included. A key to the genus Thoracochirus of mainland China species is provided. PMID- 25113681 TI - A new species of Labiobaetis Novikova & Kluge, 1987 (Ephemeroptera: Baetidae) from Washington, USA. AB - Labiobaetis sonajuventus n.sp. is described from nymphs collected in a tributary of the Okanogan River in north-central Washington, USA. The new species is distinguished from North American congeners by the well-developed keel between the bases of the antennae, the concave lateral margin of labial palp segment 2, the apically expanded submarginal setae on the labrum, and its western Nearctic distribution. PMID- 25113683 TI - Adults and larvae of two Leucochrysa (Leucochrysa) species (Neuroptera: Chrysopidae): descriptions, biological notes, and relationships. AB - This taxonomic study includes: (i) a redescription of Leucochrysa (Leucochrysa) nigrilabris (Banks) (? and ?), based on the type specimen and new material and (ii) images of the Leucochrysa (L.) insularis (Walker) type, adult color polymorphism, and genital characters (? and ?). For both species, it provides: (iii) descriptions of the larvae, (iv) biological notes, and (v) geographic records. Using the above information, we compare the two species with each other and with other Leucochrysa (Leucochrysa) species that purportedly are closely related. We conclude: First, the larval features of L. (L.) nigrilabris and L. (L.) insularis coincide with those previously described as characteristic of the genus Leucochrysa and its subgenus Leucochrysa. Second, based on their genitalia (? and ?), larval morphology, and biology (e.g., deposition of eggs in clusters), the two species are distinct, but very closely related. And, third, L. (L.) nigrilabris and L. (L.) insularis share several characteristics with the Leucochrysa (L.) "varia-like" species; these include similar adult color polymorphisms and aspects of their larval morphology. However, their genitalia (? and ?) differ significantly from those of the described L. (L.) "varia-like" species, and thus we consider the two sets of species to be distinct. PMID- 25113684 TI - A new genus and species of Discozerconidae (Acari: Mesostigmata) from carabid beetles (Coleoptera: Carabidae) in New Zealand . AB - Berzercon ferdinandi gen. nov., sp. nov. (Acari: Mesostigmata: Discozerconidae) is described from carabid beetles in New Zealand. As in all Discozerconidae, Berzercon has large ventrally-directed opisthogastric suckers. However it is distinctive in its long marginal setae, tripartite gnathotectum, fused palp tibia and tarsus, the female's large dome-shaped genital shield and the male's highly modified hypostomal seta h1. This new species also represents the first Heterozerconina from an insect host. PMID- 25113685 TI - Taxonomic review of the genus Rhinoncomimus (Coleoptera: Curculionidae: Ceutorhynchinae) with description of a new species from Yunnan, China. AB - The genus Rhinoncomimus Wagner, 1940 includes seven species from Eastern Asia. One new species, Rh. continuus sp. nov. from Yunnan, China, is described. Habitus photos, illustrations and descriptions of all species except Rh. rubripes Korotyaev, 2006 (a possible junior synonym of R. niger Chujo and Morimoto, 1959) are provided in detail, as well as key to species and distribution maps. In addition, the host plant of the type species Rh. klapperichi Wagner, 1940, Polygonum hydropiper L. (Polygonaceae) is newly recorded. PMID- 25113686 TI - Paratylenchus shenzhenensis n. sp. (Nematoda: Paratylenchinae) from the rhizosphere soil of Anthurium andraeanum in China. AB - Paratylenchus shenzhenensis n. sp. was collected from the rhizosphere soil of Anthurium andraeanum in Shenzhen, Guangdong Province, China. The new species is characterized by having a female with a small body (249-302 MUm), well developed stylet (17-21 MUm), rounded head with four submedian lobes and lip-region with a slight depression at the oral area, small post-vulval uterine sac with a few vestigial cells; male with body dorsally curved behind the cloacal opening, stylet absent, pharynx degenerate, prominent penial sheath; and juveniles with a stylet. It is morphologically similar to P. minutus. The internal transcribed spacer sequences of ribosomal DNA (ITS-rDNA) of the new species only have 72-73% identity with P. minutus, confirming its status as a separate species. The D2/D3 region of 28S ribosomal DNA (28S rDNA) and 18S small subunit ribosomal DNA (18S rDNA) from P. shenzhenensis n. sp. were also amplified and sequenced in this study. PMID- 25113687 TI - Two new species of the genus Cicadatra Kolenati (Hemiptera: Cicadidae) from Pakistan. AB - Two new species of the genus Cicadatra Kolenati, C. ashrafi sp.n. and C. tandojamensis sp.n. are described from Pakistan. Male genitalia, timbals and opercula are described and illustrated as important diagnostic characters. Host affinity for one species is also provided. A key to the known species of Pakistani Cicadatra is also given. PMID- 25113688 TI - The female of Heteropoda schwalbachorum Jager, 2008 (Araneae: Sparassidae). PMID- 25113690 TI - On the Australian linyphiid spider Alaxchelicera ordinaria Butler, 1932 (Araneae). PMID- 25113689 TI - A simple device to collect, store and study samples of two-dimensional spider webs. PMID- 25113691 TI - The use of the prefix Pan- and other problems in zoological family-series nomenclature. PMID- 25113692 TI - On the identities of Barbus mussullah Sykes and Cyprinus curmuca Hamilton with notes on the status of Gobio canarensis Jerdon (Teleostei: Cyprinidae). AB - The identity and generic placement of Barbus mussullah Sykes, the type species of Hypselobarbus Bleeker, have for long been unclear, variously having been considered a synonym of Cyprinus curmuca Hamilton or a species of Tor Gray or Gonoproktopterus Bleeker. Here, through a re-examination of the original descriptions and the examination of specimens from western peninsular India, we redescribe H. mussullah and show that Hypselobarbus is a valid genus, of which Gonoproktopertus is a junior synonym. Hypselobarbus mussullah is distinguished from all other species of Hypselobarbus by possessing both rostral and maxillary barbels; having the last simple dorsal-fin ray weak and smooth; the lateral line complete, with 41 +1 pored scales; 9/1/4 scales in transverse line between origins of dorsal and pelvic fins; and 51/2 scales between lateral line and anal fin origin. Species of Hypselobarbus are distinguished from other genera of Cyprinidae by possessing long, branched gill rakers and the anal fin distally rounded in adults. Hypselobarbus canarensis was found to be a valid species and H. kurali is considered its synonym. Hypselobarbus canarensis can be distinguished from all congeners by possessing both rostral and maxillary barbels; having the last simple dorsal-fin ray weak and smooth; the lateral line complete, with 40-42+1 pored scales; 1/27-1/28/1/31/2 scales in transverse line from dorsal-fin origin to pelvic-fin origin; 41/2 scales between lateral line and anal-fin origin. Hypselobarbus kolus is considered a synonym of H. curmuca, which is redescribed: it is distinguished from all congeners by possessing maxillary barbels only; the last simple dorsal-fin ray weak and smooth; 41-43+1 lateral line scales; 9-10/1/41/2-5 scales in transverse line between origins of dorsal and pelvic fins; and 51/2-6 scales between lateral line and anal-fin origin. PMID- 25113693 TI - Acanthoplesiops cappuccino, a new species of acanthoclinine fish from the Red Sea (Teleostei: Plesiopidae) . AB - Acanthoplesiops cappuccino is described from the 16.4 mm SL holotype collected from Jeddah, Saudi Arabia, Red Sea. The following combination of characters distinguishes it from congeners: dorsal-fin rays XVIII,4; anal-fin rays VII,4; pectoral-fin rays 18; caudal fin not connected to last rays of dorsal and anal fins by membrane; and caudal peduncle with a pale yellowish brown bar, which extends broadly on to caudal fin. An underwater photo of the anaesthetised holotype is provided, as well as one of the freshly dead holotype and only known specimen of the similar species A. naka. Tables summarizing diagnostic characters of the six known species of Acanthoplesiops are included. congeners by possessing both rostral and maxillary barbels; having the last simple dorsal-fin ray weak and smooth; the lateral line complete, with 40-42+1 pored scales; 1/27 1/28/1/31/2 scales in transverse line from dorsal-fin origin to pelvic-fin origin; 41/2 scales between lateral line and anal-fin origin. Hypselobarbus kolus is considered a synonym of H. curmuca, which is redescribed: it is distinguished from all congeners by possessing maxillary barbels only; the last simple dorsal fin ray weak and smooth; 41-43+1 lateral-line scales; 9-10/1/41/2-5 scales in transverse line between origins of dorsal and pelvic fins; and 51/2-6 scales between lateral line and anal-fin origin. PMID- 25113694 TI - Cambarus (C.) hatfieldi, a new species of crayfish (Decapoda:Cambaridae) from the Tug Fork River Basin of Kentucky, Virginia and West Virginia, USA. AB - Cambarus (Cambarus) hatfieldi is a stream-dwelling crayfish that appears to be endemic to the Tug Fork River system of West Virginia, Virginia, and Kentucky. Within this region, it is prevalent in all major tributaries in the basin as well as the Tug Fork River's mainstem. The new species is morphologically most similar to Cambarus sciotensis and Cambarus angularis. It can be differentiated from C. sciotensis by its squamous, subtrinagular chelae compared to the elongate triangular chelae of C. sciotensis; its shorter palm length/palm depth ratio (1.9) compared to C. sciotensis (2.3); and a smaller areola length/total carapace length ratio (30.4% vs.36.5% respectively). Cambarus hatfieldi can be differentiated from C. angularis by its smaller areola length/total carapace length ratio (30.4% vs. 36.7% respectively); a smaller rostrum width/rostral length ratio (59.4% vs. 67.2% respectively); its rounded abdominal pleura as compared to the subtruncated pleura of C. angularis; the length of the central projection and mesial process of C. hatfieldi which both extend to the margin of the gonopod shaft or slightly beyond the margin compared to the central projection of C. sciotensis and C. angularis where both extend well beyond the margin of the gonopod shaft. PMID- 25113695 TI - An update of the blow flies (Diptera: Calliphoridae) of the Galapagos Islands, and first record of Chrysomya rufifacies (Macquart) from mainland Ecuador. AB - Seven species of Calliphoridae are reported from the Galapagos Islands, Ecuador: Lucilia pionia (Walker), L. setosa (James), L. deceptor (Curran), L. eximia (Wiedemann), Cochliomyia macellaria (Fabricius), Chrysomya albiceps (Wiedemann), and Chrysomya megacephala (Fabricius). Lucilia eximia is newly recorded from the islands. Lucilia sp. near pionia is recorded from the island of Espanola. The distribution and collection records of these species are discussed and listed, and a key to their identification is provided. Chrysomya rufifacies (Macquart) is reported for the first time from mainland Ecuador and the identification of this species is outlined. PMID- 25113696 TI - Terataki, a new genus of Staphylinini (Coleoptera: Staphylinidae: Staphylininae) from South America. AB - A new genus of Xanthopygina is described here as Terataki gen. n. and includes the following species: Te. badiipennis comb. n., Te. caterinoi sp. n., Te. erithracus comb. n. and Te. liliputanum comb. n. Lectotypes are designated for Creophilus badiipennis Nordmann, C. chloris Nordmann, C. erithracus Nordmann and Polyphematiana liliputana Bernhauer. Creophilus chloris is shown to be a junior synonym of C. erithracus and Trigonopselaphus nobilis Wendeler a junior synonym of C. badiipennis. A key and illustrations of structural features are provided for the identification of specimens. PMID- 25113697 TI - The salmon, the lungfish (or the coelacanth) and the cow: a revival? PMID- 25113698 TI - On three monotypic nursery web spider genera from Madagascar with first description of the male of Tallonia picta Simon, 1889 and redescription of the type-species of Paracladycnis Blandin, 1979 and Thalassiopsis Roewer, 1955 (Araneae: Lycosoidea: Pisauridae). PMID- 25113699 TI - The Neotropical chloropine genus Ischnochlorops Paganelli 2002 (Diptera: Chloropidae), with the description of a new species. AB - A new species is described for the Neotropical genus Ischnochlorops Paganelli (Diptera: Chloropidae), so far known only from the type-species, I. trilineatus Paganelli. The type-species is redescribed based on an additional male from the State of Parana. A new species, I. lefevrei sp. nov., from Campos do Jordao, State of Sao Paulo, Brazil, is described. An emended diagnosis is proposed for Ischnochlorops and a key to the species is provided. Photographs of the habitus, head, and wing of both species are provided, as well as drawings of the male terminalia. PMID- 25113700 TI - A new genus and species of Vartini (Hemiptera: Cicadellidae: Deltocephalinae) from Africa. AB - A new genus and species of the leafhopper tribe Vartini are described. Afrovarta angelae gen. & sp. nov. are described based on specimens from Ghana, Cameroon, and Gabon. PMID- 25113701 TI - Morphological and acoustic characterization of Proceratophrys goyana (Lissamphibia: Anura: Odontophrynidae), with the description of a sympatric and related new species. AB - Proceratophrys goyana was until recently the only species of the genus described from central Brazil. In this paper we characterize the adult morphology and advertisement call of this species, based on data collected at its type-locality (Chapada dos Veadeiros, Goias, Brazil). These new data allowed us to recognize a new species of Proceratophrys, sympatric to P. goyana, which is described herein. Proceratophrys goyana is mainly characterized by the male SVL = 38.8-46.5 mm; a well-developed and continuous pair of dorsal sagittal ridges; upper eyelids triangular; developed frontoparietal crests, delimiting a shallow depression between them; overall color pattern browned, with the symmetrical dorsal ridges bordered laterally by dark brown undulations. Proceratophrys rotundipalpebra sp. nov. is characterized by the male SVL = 30.4-39.3 mm; the pair of symmetrical dorsal ridges well-developed anteriorly and somewhat interrupted in the sacral region; upper eyelids short and rounded; frontoparietal crests not well developed; overall color pattern stained by 3-4 tonalities of gray, without a clear background color. The advertisement calls of both species are emitted in a multi-note pattern, each note pulsed, the first and last notes differing from each other and from those amidst the call in temporal features. The description of this new species is another example of the underestimated diversity of Proceratophrys in the Cerrado of central Brazil. PMID- 25113702 TI - Three new species of Proceratophrys Miranda-Ribeiro 1920 from Brazilian Cerrado (Anura, Odontophrynidae). AB - Based on the analyses of specimens collected at several areas in the Cerrado domain from Central Brazil and others housed in scientific collections and on specimens collected at the type-locality, herein we describe three new species belonging to the P. cristiceps group: Proceratophrys bagnoi sp. nov., from UHE Serra da Mesa power plant (13 degrees 49'47.5"S, 48 degrees 19'17"W; 570 m a.s.l.; WGS84 datum), Municipality of Minacu, State of Goias; Proceratophrys branti sp. nov., from Jalapao, Municipality of Mateiros (05o15'25"S, 48o12'00"W; 109 m a.s.l.; WGS84 datum), State of Tocantins; and Proceratophrys dibernardoi sp. nov., Municipality of Mineiros (17o33'52"S, 52o33'20"W; 803 m a.s.l.; WGS84 datum), State of Goias. The diversity of Proceratophrys in Brazilian Cerrado is still underscored and several species will be described in the following years. PMID- 25113703 TI - Ultrastructure and morphometry of eggs of Triatoma rubrovaria (Blanchard, 1843), Triatoma carcavalloi Juberg, Rocha & Lent, 1998 and Triatoma circummaculata (Stal, 1859) (Hemiptera-Reduviidae-Triatominae). AB - This study analyzed the body and the operculum of eggs of Triatoma rubrovaria, T. carcavalloi and T. circummaculata, considered sylvatic species that live in sympatry.Triatoma rubrovaria is currently considered the most important vector of Trypanosoma cruzi in the rural areas of the state of Rio Grande do Sul, followed by T.circummaculata. Significant differences other than morphometry have been observed in the egg structures of the three species using traditional microscopy and scanning electron microscopy. Triatoma circummaculata eggs are smaller than those of T.rubrovaria and T. carcavalloi. The average number of perforations in corionic cells in the egg body is higher for the T. rubrovaria. The average number of perforations in the operculum cell is higher in T. circummaculata. This is the first morpho-structural description of T. carcavalloi eggs. These results widen the concept of these three species and create new subsidies for the entomological monitoring in areas in which these vectors may infest human living quarters. PMID- 25113704 TI - Two new species of Aaptos (Demospongiae, Hadromerida) from Brazil (western Atlantic). AB - Twenty-one species of Aaptos Gray, 1867 are known world-wide, of which only three were reported from Brazil. Two new species of this genus are here described from the Brazilian coast (Potiguar Basin, Northeastern Brazil): A. hajdui sp. nov. and A. potiguarensis sp. nov. Both possess only one category of strongyloxeas and one of styles, although both with wide size variation, suggesting that the diagnosis of the genus should be revised. Previous Brazilian records of A. aaptos have their status re-evaluated here, and only three species of the genus can be considered valid in Brazil: A. glutinans, A. hajdui sp. nov. and A. potiguarensis sp. nov. PMID- 25113705 TI - First zoeal stage of the partner shrimp Periclimenes paivai Chace, with remarks on the genus Periclimenes O.G. Costa (Caridea, Palaemonidae. AB - The morphology of the first zoeal stage of Periclimenes paivai Chace is described and illustrated for the first time. Larvae were obtained from three females with embryos, caught in the type locality (Cananeia, Sao Paulo state, Brazil). The morphological characters are detailed and compared with all previous descriptions of larvae in the genus (P. amethysteus, P. brevicarpalis, P. diversipes, P. pandionis, P. sagittifer and P. soror). The zoeae I of Periclimenes species are very similar, but P. paivai can be separated from the other six species by means of five characteristics: 8 plumose setae on the inner margin of the antennal scale, one spine on the endopod of the maxillule, one cuspidate seta on the basal endite of the maxilulle, one plumose seta on the single coxal endite of the maxilla, and one plumose seta on the endopod of the maxilla. Remarks from a comparative analysis of available descriptions of the genus are furnished. PMID- 25113706 TI - Cliona tumula sp. nov., a conspicuous, massive Symbiodinium-bearing clionaid from the lower Florida Keys (USA)(Demospongiae: Hadromerida: Clionaidae). AB - Cliona tumula sp. nov. is described from the Florida Keys, Florida, USA. The new species is compared to representative Cliona spp. from the Caribbean and Indo Pacific. Cliona tumula sp. nov. is a massive, mound-shaped zooxanthellate clionaid with a central, apical cluster of numerous oscula, slender tylostyles with variable heads and abundant, delicate spirasters with compound spines that can be concentrated at the ends, which in this species can appear as mushroom like caps, with a skeleton in typical clionaid arrangement. It is distinguished from congeners by its epibenthic growth form that extends for 20-40 cm above the substratum, centrally located concentration of oscula, and calcareous fragments obtained from surrounding sediment that C. tumula sp. nov. incorporates in tracts that run through the choanosome perpendicular to the ectosome. This species can be locally abundant in the Florida Keys in patch reefs near sand flats, but may be restricted to the lower keys as it has not been observed on reefs to the east. PMID- 25113707 TI - Three new species of the tribe Meconematini (Orthoptera: Tettigoniidae) from Taiwan. AB - The paper reported three new species from Taiwan, i.e. Xizicus (Eoxizicus) taiwanensis sp. nov., Xizicus (Axizicus) falcata sp. nov. and Decma (Decma) brachyptera sp. nov., supplied the descriptions and illustrations. PMID- 25113708 TI - New species of Fannia Robineau-Desvoidy (Diptera: Fanniidae) from Colombia. AB - Fannia Robineau-Desvoidy is a genus of calyptrate Diptera that comprises 89 Neotropical species, of which only 23 occur in Colombia. Based on male characters (including terminalia), two new species from the Department of Antioquia (Fannia colazorrensis sp. nov. and Fannia laclara sp. nov.) are described. Illustrations of the male are presented. PMID- 25113709 TI - Two new species of Dryophthorinae in the genera Metamasius and Melchus from the Lesser Antilles (Coleoptera: urculionidae). AB - Metamasius planatus and Melchus jessae, are described and illustrated from the Lesser Antilles islands of Dominica and St. Lucia. Metamasius planatus (Dominica) is distinguished by a relatively flat profile and presence of dense, very fine, golden micropilosity covering most of the dorsal surface. Melchus jessae (Dominica and St. Lucia) is the sixth species known in the genus and is distinguished by the cylindrical rostrum (not laterally compressed apically). Information on natural history for both species is limited: some Metamasius planatus and one Melchus jessae were collected in bases of Euterpe globosa fronds. A revised key to genera of Neotropical Litosomini is presented. PMID- 25113710 TI - The genus Colletes (Hymenoptera: Apoidea: Colletidae) in Central Asia . AB - Available information about bees of the genus Colletes in Central Asia is summarized. Eighty species are currently known from this area. Six new species are described: Colletes transitus sp. nov., C. askhabadoides sp. nov., C. kaline sp. nov., C. muellermotzfeldi sp. nov., C. pesenkoi sp. nov., and C. mirabilis sp. nov. Five species are newly recorded from Central Asia: Colletes idoneus Cockerell 1922, C. cunicularius (Linnaeus 1761), C. ebmeri Kuhlmann 2002, C. friesei Cockerell 1918, and C. impunctatus Nylander 1852. The subspecies C. tuberculatus anatolicus Noskiewicz 1959 syn. nov. and C. t. siculus Noskiewicz 1959 syn. nov. are synonymized with C. tuberculatus Morawitz 1894. Lectotypes are designated for Colletes arenarius Morawitz 1876 and C. flavicornis Morawitz 1876. Additionally one new species from Turkey and Iran, Colletes comatoides sp. nov., is here described as new and included due to its close relationship to the Central Asian C. bernadettae Kuhlmann and C. comatus Noskiewicz. PMID- 25113711 TI - Redescription and lectotype designation of the endemic South African mayfly Lestagella penicillata (Barnard, 1932) (Ephemeroptera: Teloganodidae). AB - The imago and nymph of Lestagella penicillata are redescribed based on historic specimens and new material from Table Mountain slopes (Skeleton Gorge and Window Stream), Western Cape, South Africa. A male from Barnard's syntype series is designated as the lectotype. Wear-and-tear of mouthparts, particularly the mandibles, has led to errors in identification of diagnostic characters for the nymphs in earlier publications. Previous descriptions of the mandibles being atrophied, in terms of dentition, are erroneous. The generic diagnosis of Lestagella is modified to account for these errors and intraspecific variability. Adults are distinguished from other Teloganodidae by the combination of a short, detached iMP vein on the forewing, three caudal filaments and gill socket vestiges on segments II - IV. Nymphs are distinguished from other Teloganodidae by a conspicuous head fringe, lamellate gills on abdominal segments II-IV and a dorso-ventrally flattened body. PMID- 25113712 TI - A molecular phylogeny of the African plated lizards, genus Gerrhosaurus Wiegmann, 1828 (Squamata: Gerrhosauridae), with the description of two new genera. AB - We constructed a molecular phylogeny of the African plated lizard family Gerrhosauridae using two mitochondrial markers (ND2, 732 bp; 16S, 576 bp) and one nuclear marker (PRLR, 538 bp). This analysis showed that the subfamily Gerrhosaurinae consists of five major clades which we interpret as representing five genera. The genera Tetradactylus and Cordylosaurus were each recovered as monophyletic, but Gerrhosaurus as currently conceived is paraphyletic, consisting of three distinct genus-level assemblages. The two clades consisting of Gerrhosaurus major Dumeril, 1851 and Gerrhosaurus validus Smith, 1849 are both described here as new genera, namely Broadleysaurus Bates & Tolley gen. nov. and Matobosaurus Bates & Tolley gen. nov., respectively. Two subspecies of 'Gerrhosaurus major' that were historically separated on the basis of differences in colour pattern are not reciprocally monophyletic, so Gerrhosaurus bottegoi Del Prato, 1895 is relegated to the synonomy of Broadleysaurus major (Dumeril, 1851) comb. nov., which is rendered monotypic. Gerrhosaurus validus maltzahni De Grys, 1938 is genetically and morphologically well differentiated from G. v. validus and the two taxa also occur in allopatry. We therefore re-instate the former as Matobosaurus maltzahni (De Grys, 1938) comb. nov., rendering Matobosaurus validus (Smith, 1849) comb. nov. a monotypic species. Our analysis also showed that Gerrhosaurus sensu stricto comprises two major subclades, one consisting of Gerrhosaurus typicus (Smith, 1837) + Gerrhosaurus skoogi Andersson, 1916, and the other containing the remaining species. In this latter subclade we show that west Central African Gerrhosaurus nigrolineatus Hallowell, 1857 is most closely related to Gerrhosaurus auritus Boettger, 1887 rather than to G. nigrolineatus from East and Southern Africa. The west-Central African clade of G. nigrolineatus differs from the East and Southern African clade by a p-distance of 13.0% (ND2) and 6.9% (16S), and can be differentiated morphologically. We accordingly apply the name Gerrhosaurus intermedius Lonnberg, 1907 comb. nov. to populations from Kenya, Uganda, Rwanda, Tanzania, Malawi, Mozambique, Zimbabwe and South Africa previously identified under the name G. nigrolineatus. Our analysis also confirms that Gerrhosaurus bulsi Laurent, 1954 is a distinct species and sister taxon to a clade containing G. nigrolineatus, G. auritus and G. intermedius. The latter four taxa form a closely-related 'G. nigrolineatus species complex' with a widespread distribution in Africa. Most closely related to this complex of species is Gerrhosaurus flavigularis Wiegmann, 1828 which has an extensive range in East and Southern Africa, and displays genetic substructure which requires further investigation. The status of Gerrhosaurus multilineatus Bocage, 1866, and Angolan populations referred to G. nigrolineatus, remains problematic. PMID- 25113713 TI - Review of the Neotropical species of Stauropoctonus Brauns, 1889 (Hymenoptera: Ichneumonidae: Ophioninae). AB - The taxonomy of Neotropical species of Stauropoctonus is reviewed, with redescriptions of S. bicarinatus and S. excarinatus, the description of four new Brazilian species, S. amazonensis sp. n., S. leotacilioi sp. n., S. michelle sp. n., and S. rectus sp. n., and for the first time with a detailed study of the male genitalia of the genus. Additionally, we provide a key to the world Stauropoctonus species. PMID- 25113714 TI - Taxonomic study of the genus Scaphoideus Uhler (Hemiptera, Cicadellidae, Deltocephalinae) from Japan. AB - The Japanese species of the genus Scaphoideus are revised. Eight species are recognized from Japan, including four new species: S. ryukyuensis sp. nov. from the Ryukyus, S. pristiophorus sp. nov. from Honshu and Kyushu, S. aurantius sp. nov. from the Ryukyus and S. brevistylus sp. nov. from Honshu, Kyushu and the Ryukyus. PMID- 25113715 TI - Bird fossils from Ankilitelo Cave: inference about Holocene environmental changes in southwestern Madagascar. AB - The identifications of non-permineralized fossil bird bones recovered from Ankilitelo Cave in southwestern Madagascar are presented. Among the more than 560 elements recovered, 29 different taxa were identified, the vast majority being species that still occur in this region of the island. Eggshell remains from the extinct elephant bird (Family Aepyornithidae) and assigned to Aepyornis sp. were found at the site. Two identified extant taxa, Scopus umbretta and Monias benschi, no longer occur in the area immediately surrounding the cave. The available radiocarbon measurements of collagen from fossil bird bones and avian eggshell carbonate of recovered from the cave range from 13,270 Cal yr BP to modern times. Hence, the presumed ecological shifts that took place resulting in the disappearance or range contractions of these three taxa is within the Holocene and are presumed to be associated with natural climatic change and in more recent centuries associated human pressures. Information is also presented on the origin of guinea fowl (Numida) and inference on the period of colonization of Corvus albus on Madagascar. PMID- 25113716 TI - Revision of the Neotropical genus Alloraphes Franz (Coleoptera: Staphylinidae: Scydmaeninae). AB - The Neotropical genus Alloraphes Franz belonging to the tribe Cyrtoscydmini is revised. Alloraphes is redefined based on a detailed morphological study, and Parastenichnaphes myrmecophilus (Franz) is transferred back to Alloraphes, where it was originally placed. Alloraphes jamaicae Franz, A. peruanus Franz, A. lenkoi Franz, A. yucatani Franz, A. chiapasensis Franz and A. myrmecophilus Franz, stat. rest. are redescribed; A. dentatus sp. n. from Peru and A. peckorum sp. n. from Bolivia are described. Alloraphes magnus Franz and A. bolivarensis Franz are treated as species inquirendae pending further study. The placement of ?Alloraphes magnus, known from a single female only, remains unclear. The type material of A. bolivarensis was not found in the Franz Collection and the original description hardly allows for the species identification. PMID- 25113717 TI - A new species of the genus Pristimantis (Amphibia, Craugastoridae) associated with the moderately elevated massifs of French Guiana. AB - We describe a new Pristimantis from French Guiana, northern South America, which is mainly distinguished from known phenotypically related congeners (i.e. species from the polyphyletic unistrigatus species group) occurring at low and middle elevations in the Guiana Shield by the combination of a distinct tympanum, a lower ratio of tibia vs. hand length, a reddish groin region, and a distinct advertisement call consisting of clusters of generally four short notes. The new species inhabits pristine primary forests on the slopes of isolated massifs reaching more than 400 m elevation, and seems not to occur below ca. 200 m above sea level. Such a sharp altitudinal limit suggests a strong influence of thermal variation on the distribution of the species, and therefore a potential sensitivity to climate change. With only nine isolated populations documented so far, the new species should be prioritized for conservation. Historical climate fluctuations during the Quaternary are likely responsible for the distribution pattern of the new species. PMID- 25113718 TI - The genus Leucophenga (Diptera, Drosophilidae), part III: the interrupta species group from the Oriental region, with morphological and molecular evidence. AB - A new species group, the interrupta group, is established within the genus Leucophenga based on two known and three new species, all of which are endemic to the Oriental region: L. interrupta Duda, 1924, L. neointerrupta Fartyal & Toda, 2005, L. bifurcata sp. nov., L. quadrifurcata sp. nov. and L. retifoliacea sp. nov. A key to the five species of the interrupta group is provided. Sixteen mtDNA COI sequences of the five species are analyzed; the molecular data are used as complementary evidence for the species boundaries defined by the morphological data. PMID- 25113719 TI - WITHDRAWN: The Impact of Skills Training on Cognitive Functioning in Older People with Serious Mental Illness. PMID- 25113721 TI - [Infections due to unusual bacteria and bacterial oncogenesis]. AB - The recovery of an unusual organism in the clinical microbiology laboratory may be an indicator of an immunological abnormality in the patient. For instance, an important relationship between Clostridium septicum and colon carcinoma as well as between leukemia or lymphoma with species frequently considered contaminants (Bacillus spp., Corynebacterium spp.) or others rarely isolated from different contexts (Capnocytophaga spp.) were described. Some bacteria are almost exclusively isolated from AIDS patients (Rhodococcus equi). Campylobacter spp., Aeromonas spp., group G and mitis group streptococci were more frequently isolated in individuals suffering from any type of cancer than in other patients. Furthermore, some other bacteria can be considered markers of an undetected cancer that can be found mostly in neutropenic patients rather than in immunologically normal individuals. Possible mechanisms of bacterial oncogenesis include a modification of the inflammatory response, antigen-derived lymphoproliferation, and induction of hormones that increase epithelial cell proliferation. Typical examples of the above are: gastric adenocarcinoma induced by Helicobacter pylori, the association between group bovis bacteremia and colon carcinoma and the mucosa-associated lymphoid tissue (MALT) related to Helicobacter species (gastric MALT) and Chlamydophila spp. (ocular MALT). Isolation of any of these pathogens should require a thorough search for possible malignant diseases. PMID- 25113720 TI - A Longitudinal Study of the Outcome and Associated Factors of Subsyndromal and Syndromal Depression in Community-Dwelling Older Adults with Schizophrenia Spectrum Disorder. AB - OBJECTIVE: Studies examining depression in older adults with schizophrenia have been limited by cross-sectional data. This study examines longitudinal changes in depression, predictors of depression, and the impact of depression on clinical and psychosocial variables in this population. METHODS: The sample consisted of 104 community-dwelling persons with schizophrenia spectrum disorder aged 55 and over who developed the disorder before age 45. Mean follow-up was 54 months (range: 12-116 months), mean age was 61 years, 55% were men, and 55% were white. Presence of subsyndromal or syndromal depression (SSSD) was defined as scoring >7 on the Center for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: There were no significant differences in SSSD rates between interviews (61% baseline; 54% follow-up); 44% of the sample had SSSD at both assessments, 30% did not have SSSD at either assessment, 16% went from SSSD to nondepression, and 10% went from nondepression to SSSD. Similarly, 20%, 27%, and 53% of the sample exhibited >0.5 effect size increase, decrease, or no change, respectively, in their CES-D scores between assessments. There were two significant time 1 predictors of SSSD at time 2: SSSD and greater number of psychotropic medications. SSSD at time 1 predicted having higher time 2 anxiety scores. CONCLUSION: Persistent ("core") depression occurs in about two-fifths of persons, 30% remain persistently nondepressed, and one-fourth may fluctuate between depression and nondepression. No association was found between depression and most predictor variables. This study supports recent findings that schizophrenia in later life is not a quiescent state or one of affective withdrawal. PMID- 25113723 TI - Preoperative evaluation of the vascular surgery patient. AB - Patients undergoing vascular surgery present a myriad of perioperative challenges due to the complex comorbidities affecting them in conjunction with high-risk surgical procedures. Additionally, advances in endovascular technology have enabled surgical procedures to be performed on patients who would not have been considered surgical candidates in the past. This combination of increasing patient morbidity and evolving surgical technique requires a well-planned preoperative assessment and close communication with surgical and perioperative colleagues. This article outlines an appropriate approach by first considering each organ system, followed by review of considerations unique to various surgical procedures, and then an overall assessment of risk. PMID- 25113724 TI - Optimal perioperative medical management of the vascular surgery patient. AB - Perioperative medical management of patients undergoing vascular surgery can be challenging because they represent the surgical population at highest risk. beta Blockers should be continued perioperatively in patients already taking them preoperatively. Statins may be used in the perioperative period in patients who are not on statin therapy preoperatively. Institutional guidelines should be used to guide insulin replacement. Recent research suggests that measurement of troponins may provide some risk stratification in clinically stable patients following vascular surgery. Multimodal pain therapy including nonopioid strategies is necessary to improve the efficacy of pain relief and decrease the risk of side effects and complications. PMID- 25113725 TI - Regional anesthesia for vascular surgery. AB - Patients presenting for vascular surgery present a challenge to anesthesiologists because of their severe systemic comorbidities. Regional anesthesia has been used as a primary anesthetic technique for many vascular procedures to avoid the cardiovascular and pulmonary perturbations associated with general anesthesia. In this article the use of regional anesthesia for carotid endarterectomy, open and endovascular abdominal aortic aneurysm repair, infrainguinal arterial bypass, lower extremity amputation, and arteriovenous fistula formation is described. A focus is placed on reviewing the literature comparing anesthetic techniques, with brief descriptions of the techniques themselves. PMID- 25113726 TI - Perioperative management of lower extremity revascularization. AB - Patients presenting for lower extremity revascularization often have multiple systemic comorbidities, making them high-risk surgical candidates. Neuraxial anesthesia and general anesthesia are equivocal in their effect on perioperative cardiac morbidity and improved graft patency. Postoperative epidural analgesia may improve perioperative cardiac morbidity. Systemic antithrombotic and anticoagulation therapy is common among this patient population and may affect anesthetic techniques. PMID- 25113727 TI - Intraoperative management of carotid endarterectomy. AB - First reports on surgical treatment of cerebrovascular atherosclerosis date to the early 1950s. With advancements in surgical technique, carotid endarterectomy (CEA) has become the treatment of choice for patients with both symptomatic and asymptomatic severe carotid stenosis. Given the benefits that surgery offers beyond medical management, the number of CEA procedures continues to increase. The intraoperative management of patients undergoing CEA is challenging because of the combination of patient and surgical factors. This article explores and reviews the literature on anesthetic management and considerations of patients undergoing CEA. PMID- 25113728 TI - Perioperative management of combined carotid and coronary artery bypass grafting procedures. AB - The objective of this review is to provide a high level overview on current thinking for treatment of patients with combined carotid and coronary artery disease given that these patients are at higher risk of adverse cardiac events, stroke, and death. This review discusses (1) the current literature addressing perioperative stroke risk in the setting of coronary artery bypass graft, (2) the literature regarding different surgical approaches when both carotid and coronary revascularization are being considered, and (3) the data available to guide optimal management of this complex patient population to minimize complications regardless of the surgical approach taken. PMID- 25113729 TI - Considerations for patients undergoing endovascular abdominal aortic aneurysm repair. AB - Endovascular aneurysm repair has taken over open surgery as the primary strategy for treatment of patients with abdominal and thoracic aneurysms. The minimally invasive nature of these techniques requires alterations in preoperative workup, intraoperative management, and familiarity with unique complications that can occur. Familiarity from the anesthetic standpoint of endovascular techniques, including treatment of patients with fenestrated, chimney, snorkel, and periscope grafts, is necessary for the contemporary cardiac anesthesiologist. PMID- 25113730 TI - Postoperative ICU management of vascular surgery patients. AB - Critical care management of vascular surgical patients poses significant challenges owing to patients' comorbidities and the magnitude of the surgical procedures. The primary goals of the anesthesiologist and intensivist are reestablishing preoperative homeostasis, optimizing hemodynamics until return of normal organ function, and managing postoperative complications promptly and effectively. Postoperative critical care management demands a detailed knowledge of the various vascular surgical procedures and the potential postoperative complications. In this review, the authors describe the postoperative complications related to the major specific vascular surgical procedures and their perioperative management. PMID- 25113732 TI - Vascular anesthesia. Preface. PMID- 25113734 TI - Structure and photoluminescence studies of CeO2.CuAlO2 mixed metal oxide fabricated by co-precipitation method. AB - A novel mixed metal oxide, CeO2.CuAlO2 was fabricated by co-precipitation method in aqueous medium. CeO2.CuAlO2 was characterized by XRD, SEM, EDS, TEM, FTIR and PL spectra. The optical properties of the nanoparticles were studied by photoluminescence (PL) spectra. PL spectra at different excitations were recorded. The composite showed emission in UV, visible and NIR region depending on the excitation wavelength. The special spectral feature observed for this composite is that it showed six emission bands at 364, 409, 434, 448, 465 and 481 nm when excited at 298 nm. The green and red emissions observed at 512 and 669 nm are originated from cubic CeO2 phase when excited at 450 nm. The PL spectra were found to be dependent on excitation wavelength violating Kasha's rule. The X-ray diffraction reveals a cubic CeO2 phase and hexagonal CuAlO2 phase. EDS spectra revealed the presence of cerium (Ce), copper (Cu), aluminum (Al) and oxygen (O) elements. The particle size of the CeO2.CuAlO2 mixed oxide was estimated using Scherrer's formula, which was found to be in the range of 17.2-34.2 nm. The TEM image showed particles are almost uniform size of approximately 15-50 nm with spherical morphology. PMID- 25113733 TI - Continuous dopaminergic stimulation (CDS)-based treatment in Parkinson's disease patients with motor complications: a systematic review and meta-analysis. AB - A systematic review of the literature was conducted to identify randomized trials involving continuous dopaminergic stimulation (CDS) in PD patients with motor complications. Difference between n groups was assessed by partitioning heterogeneity and using the chi2 distribution with n-1 degrees of freedom, where n equals the number of groups. We looked for publication bias using funnel plotting, Egger's test and Begg's test. Twenty Randomized Controlled Trials (RCTs) were included. The results showed that CDS could evidently improve the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (p < 0.0001), part III (P < 0.00001) and UPDRS total score (p < 0.00001). There was also a statistical discrepancy in off time reduction (p < 0.00001) and prolongation of on time (p < 0.00001) by the CDS therapy compared with control groups. Meanwhile, the results of this study showed obvious side effects in the CDS therapy compared with the placebo, especially at the expense of increased dyskinesia (23.4% vs 11.7%). The present study showed that CDS was beneficial in the treatment of PD patients with motor complications. But the incidence of the side events is more common than placebo. PMID- 25113735 TI - Validated spectrofluorimetric method for determination of selected aminoglycosides. AB - New, sensitive, and selective spectrofluorimetric method was developed for determination of three aminoglycoside drugs in different dosage forms, namely; neomycin sulfate (NEO), tobramycin (TOB) and kanamycin sulfate (KAN). The method is based on Hantzsch condensation reaction between the primary amino group of aminoglycosides with acetylacetone and formaldehyde in pH 2.7 yielding highly yellow fluorescent derivatives measured emission (471 nm) and excitation (410 nm) wavelengths. The fluorescence intensity was directly proportional to the concentration over the range 10-60, 40-100 and 5-50 ng/mL for NEO, TOB and KAN respectively. The proposed method was applied successfully for determination of these drugs in their pharmaceutical dosage forms. PMID- 25113737 TI - Switchable regioselectivity in the PIFA-BF3.Et2O mediated oxidative coupling of meso-brominated Ni(II) porphyrin. AB - A simple and efficient method has been developed for the switchable synthesis of directly linked meso-brominated Ni(II) porphyrin dimers through PIFA-BF3.Et2O mediated oxidative coupling. The respective syntheses of meso-meso or meso-beta singly, doubly, and triply linked porphyrin dimers can be easily realized with the same reagent system. PMID- 25113736 TI - Application of central composite design for simultaneous removal of methylene blue and Pb(2+) ions by walnut wood activated carbon. AB - Activated carbon was prepared from walnut wood which was locally available, non toxic, abundant and cheap. This new adsorbent was characterized using BET, FTIR and SEM. Point of zero charge (pHpzc) and oxygen containing functional groups were also determined. The prepared adsorbent was applied for simultaneous removal of Pb(2+) ions and methylene blue (MB) dye from aqueous solution. The prominent effect and interaction of variables such as amount of adsorbent, contact time, concentration of MB and Pb(2+) ions were optimized by central composite design. The equilibrium data obtained at optimum condition were fitted to conventional isotherm models and found that Langmuir model was the best fitted isotherm. Kinetic data were fitted using various models. It was revealed that the adsorption rate follows pseudo-second order kinetic model and intraparticle diffusion model. PMID- 25113738 TI - Synthesis of a poly-pendant 1-D chain based on 'trans-vanadium' bicapped, Keggin type vanadtungstate and its photocatalytic properties. AB - A vanadtungstate cluster-based organic-inorganic hybrid material [NiL4V(IV)W(VI)10W(V)2O40(V(IV)O)2] (1, L = 1,4-bis(imidazol-1-ylmethyl)benzene) was synthesized and characterized by elemental analysis, IR spectra, thermal gravimetric analysis, and single crystal X-ray diffraction analysis. Structural analysis reveals that compound 1 contains a transition metal-centered, bicapped Keggin-type {VW12O40(VO)2} core, connected by nickel linkers into a 1-D chain. These 1D chains interdigitated with each other, achieving an interdigitated 3D supermolecular architecture. Photocatalytic studies indicate that compound 1 exhibits not only active photocatalytic degradation of dye molecules, but also selective photocatalytic activity for degradation of cationic dyes in aqueous solution. Further, this photocatalyst is stable and easily separated from the photocatalytic system for reuse as well. PMID- 25113739 TI - Inverse association between cancer and neurodegenerative disease: review of the epidemiologic and biological evidence. AB - Growing evidence suggests an unusual epidemiologic association between cancer and certain neurological conditions, particularly age-related neurodegenerative diseases. Cancer survivors have a 20-50% lower risk of developing Parkinson's and Alzheimer's disease, and patients with these neurodegenerative conditions have a substantially lower incidence of cancer. We review the epidemiologic evidence for this inverse co-morbidity and show that it is not simply an artifact of survival bias or under-diagnosis. We then review the potential biological explanations for this association, which is intimately linked to the very different nature of dividing cells and neurons. The known genetic and metabolic connections between cancer and neurodegeneration generally fall within two categories. The first includes shared genes and pathways such as Pin1 and the ubiquitin proteasome system that are dysregulated in different directions to cause one disease or the other. The second includes common pathophysiological mechanisms such as mitochondrial dysfunction, oxidative stress and DNA damage that drive both conditions, but with different cellular fates. We discuss examples of these biological links and their implications for developing new approaches to prevention and treatment of both diseases. PMID- 25113740 TI - International recognition for ageing research: John Scott Award-2014 to Leonard Hayflick and Paul Moorhead. PMID- 25113741 TI - Does bird species diversity vary among forest types? A local-scale test in southern Chile. AB - Birds are the most diverse vertebrate group in Chile, characterized by low species turnover at the country-size scale (high alpha but low beta diversities), resembling an island biota. We tested whether this low differentiation is valid at a local scale, among six forest habitat types. We detected 25 bird species; avifauna composition was significantly different among habitat types, with five species accounting for 60% of the dissimilarity. We found a higher level of bird assemblage differentiation across habitats at the local scale than has been found at the country-size scale. Such differentiation might be attributed to structural differences among habitats. PMID- 25113742 TI - Streptococcal pharyngitis in children: to treat or not to treat? AB - Controversy remains about the need for antibiotic therapy of group A streptococcal (GAS) pharyngitis in high-resource settings. Guidelines on the management of GAS pharyngitis differ considerably, especially in children. We performed a literature search on the diagnosis and treatment of GAS pharyngitis in children and compared different guidelines with current epidemiology and the available evidence on management. Some European guidelines only recommend antibiotic treatment in certain high-risk patients, while many other, including all American, still advise antimicrobial treatment for all children with GAS pharyngitis, given the severity and re-emerging incidence of complications. Empirical antimicrobial treatment in children with sore throat and a high clinical suspicion of GAS pharyngitis will still result in significant overtreatment of nonstreptococcal pharyngitis. This is costly and leads to emerging antibiotic resistance. Early differential diagnosis between viral and GAS pharyngitis, by means of a 'rapid antigen detection test' (RADT) and/or a throat culture, is therefore needed if 'pro treatment' guidelines are used. CONCLUSION: Large scale randomized controlled trials are necessary to assess the value of antibiotics for GAS pharyngitis in high-resource countries, in order to achieve uniform and evidence-based guidelines. The severity and the possibly increasing incidence of complications in school-aged children suggests that testing and treating proven GAS pharyngitis can still be beneficial. PMID- 25113743 TI - Inclusion of mobile telephone numbers into an ongoing population health survey in New South Wales, Australia, using an overlapping dual-frame design: impact on the time series. AB - BACKGROUND: Since 1997, the NSW Population Health Survey (NSWPHS) had selected the sample using random digit dialing of landline telephone numbers. When the survey began coverage of the population by landline phone frames was high (96%). As landline coverage in Australia has declined and continues to do so, in 2012, a sample of mobile telephone numbers was added to the survey using an overlapping dual-frame design. Details of the methodology are published elsewhere. This paper discusses the impacts of the sampling frame change on the time series, and provides possible approaches to handling these impacts. METHODS: Prevalence estimates were calculated for type of phone-use, and a range of health indicators. Prevalence ratios (PR) for each of the health indicators were also calculated using Poisson regression analysis with robust variance estimation by type of phone-use. Health estimates for 2012 were compared to 2011. The full time series was examined for selected health indicators. RESULTS: It was estimated from the 2012 NSWPHS that 20.0% of the NSW population were mobile-only phone users. Looking at the full time series for overweight or obese and current smoking if the NSWPHS had continued to be undertaken only using a landline frame, overweight or obese would have been shown to continue to increase and current smoking would have been shown to continue to decrease. However, with the introduction of the overlapping dual-frame design in 2012, overweight or obese increased until 2011 and then decreased in 2012, and current smoking decreased until 2011, and then increased in 2012. Our examination of these time series showed that the changes were a consequence of the sampling frame change and were not real changes. Both the backcasting method and the minimal coverage method could adequately adjust for the design change and allow for the continuation of the time series. CONCLUSIONS: The inclusion of the mobile telephone numbers, through an overlapping dual-frame design, did impact on the time series for some of the health indicators collected through the NSWPHS, but only in that it corrected the estimates that were being calculated from a sample frame that was progressively covering less of the population. PMID- 25113744 TI - Altered phenotype and Stat1 expression in Toll-like receptor 7/8 stimulated monocyte-derived dendritic cells from patients with primary Sjogren's syndrome. AB - INTRODUCTION: Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system, involved in both initiating immune responses and maintaining tolerance. Dysfunctional and via toll-like receptor (TLR) ligands activated DC have been implicated in the development of autoimmune diseases, but their role in the etiology of Sjogren's syndrome, a chronic inflammatory autoimmune disease characterized by progressive mononuclear cell infiltration in the exocrine glands, has not been revealed yet. Therefore, the aim of this study was to investigate phenotype and functional properties of immature and TLR7/8 stimulated monocyte-derived DC (moDC) of patients with primary Sjogren's syndrome (pSS) and compare them to healthy controls. METHODS: The phenotype, apoptosis susceptibility and endocytic capacity of moDC were analyzed by flow cytometry. Secretion of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and multiplex Luminex analyses in moDC cell culture supernatants. The expression of TLR7 was analyzed by flow cytometry and real-time quantitative polymerase chain reaction (qPCR). Expression of Ro/Sjogren's syndrome-associated autoantigen A (Ro52/SSA), interferon regulatory factor 8 (IRF-8), Bim, signal transduction and activators of transcription (Stat) 1, p-Stat1 (Tyrosin 701), p-Stat1 (Serin 727), Stat3, pStat3 (Tyrosin 705) and glyceraldehyde 3-phosphatase dehydrogenase (GAPDH) was measured by Western blotting. Nuclear factor kappa-light-chain enhancer of activated B cells (NF-kappaB) family members were quantified using the ELISA-based TransAM NF-kappaB family kit. RESULTS: We could not detect differences in expression of co-stimulatory molecules and maturation markers such as cluster of differentiation (CD) 86, CD80, CD40 or CD83 on moDC from patients compared to healthy controls. Moreover, we could not observe variations in apoptosis susceptibility, Bim and Ro52/SSA expression and the endocytic capacity of the moDC. However, we found that moDC from pSS patients expressed increased levels of the major histocompatibility complex (MHC) class II molecule human leukocyte antigen (HLA)-DR. We also found significant differences in cytokine production by moDC, where increased interleukin (IL)-12p40 secretion in mature pSS moDC correlated with increased RelB expression. Strikingly, moDC from pSS patients matured for 48 hours with TLR7/8 ligand CL097 expressed significantly less Stat1. CONCLUSION: Our results suggest a role for moDC in the pathogenesis of Sjogren's syndrome. PMID- 25113745 TI - Chikungunya virus was isolated in Thailand, 2010. AB - Chikungunya fever (CHIKF) is an acute febrile illness caused by a mosquito-borne alphavirus, chikungunya virus (CHIKV). This disease re-emerged in Kenya in 2004, and spread to the countries in and around the Indian Ocean. The re-emerging epidemics rapidly spread to regions like India and Southeast Asia, and it was subsequently identified in Europe in 2007, probably as a result of importation of chikungunya cases. On the one hand, chikungunya is one of the neglected diseases and has only attracted strong attention during large outbreaks. In 2008-2009, there was a major outbreak of chikungunya fever in Thailand, resulting in the highest number of infections in any country in the region. However, no update of CHIKV circulating in Thailand has been published since 2009. In this study, we examined the viral growth kinetics and sequences of the structural genes derived from CHIKV clinical isolates obtained from the serum specimens of CHIKF-suspected patients in Central Thailand in 2010. We identified the CHIKV harboring two mutations E1-A226V and E2-I211T, indicating that the East, Central, and South African lineage of CHIKV was continuously circulating as an indigenous population in Thailand. PMID- 25113746 TI - A murine model of neurofibromatosis type 2 that accurately phenocopies human schwannoma formation. AB - Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disorder resulting from germline mutations in the NF2 gene. Bilateral vestibular schwannomas, tumors on cranial nerve VIII, are pathognomonic for NF2 disease. Furthermore, schwannomas also commonly develop in other cranial nerves, dorsal root ganglia and peripheral nerves. These tumors are a major cause of morbidity and mortality, and medical therapies to treat them are limited. Animal models that accurately recapitulate the full anatomical spectrum of human NF2-related schwannomas, including the characteristic functional deficits in hearing and balance associated with cranial nerve VIII tumors, would allow systematic evaluation of experimental therapeutics prior to clinical use. Here, we present a genetically engineered NF2 mouse model generated through excision of the Nf2 gene driven by Cre expression under control of a tissue-restricted 3.9kbPeriostin promoter element. By 10 months of age, 100% of Postn-Cre; Nf2(flox/flox) mice develop spinal, peripheral and cranial nerve tumors histologically identical to human schwannomas. In addition, the development of cranial nerve VIII tumors correlates with functional impairments in hearing and balance, as measured by auditory brainstem response and vestibular testing. Overall, the Postn-Cre; Nf2(flox/flox) tumor model provides a novel tool for future mechanistic and therapeutic studies of NF2-associated schwannomas. PMID- 25113749 TI - Coronary artery disease: Predicting the progression of coronary artery calcification. PMID- 25113747 TI - Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia. AB - Inherited deficiency in the mitochondrial protein frataxin (FXN) causes the rare disease Friedreich's ataxia (FA), for which there is no successful treatment. We identified a redox deficiency in FA cells and used this to model the disease. We screened a 1600-compound library to identify existing drugs, which could be of therapeutic benefit. We identified the topical anesthetic dyclonine as protective. Dyclonine increased FXN transcript and FXN protein dose-dependently in FA cells and brains of animal models. Dyclonine also rescued FXN-dependent enzyme deficiencies in the iron-sulfur enzymes, aconitase and succinate dehydrogenase. Dyclonine induces the Nrf2 [nuclear factor (erythroid-derived 2) like 2] transcription factor, which we show binds an upstream response element in the FXN locus. Additionally, dyclonine also inhibited the activity of histone methyltransferase G9a, known to methylate histone H3K9 to silence FA chromatin. Chronic dosing in a FA mouse model prevented a performance decline in balance beam studies. A human clinical proof-of-concept study was completed in eight FA patients dosed twice daily using a 1% dyclonine rinse for 1 week. Six of the eight patients showed an increase in buccal cell FXN levels, and fold induction was significantly correlated with disease severity. Dyclonine represents a novel therapeutic strategy that can potentially be repurposed for the treatment of FA. PMID- 25113748 TI - An ALS-mutant TDP-43 neurotoxic peptide adopts an anti-parallel beta-structure and induces TDP-43 redistribution. AB - TDP-43 proteinopathies are clinically and genetically heterogeneous diseases that had been considered distinct from classical amyloid diseases. Here, we provide evidence for the structural similarity between TDP-43 peptides and other amyloid proteins. Atomic force microscopy and electron microscopy examination of peptides spanning a previously defined amyloidogenic fragment revealed a minimal core region that forms amyloid fibrils similar to the TDP-43 fibrils detected in FTLD TDP brain tissues. An ALS-mutant A315E amyloidogenic TDP-43 peptide is capable of cross-seeding other TDP-43 peptides and an amyloid-beta peptide. Sequential Nuclear Overhauser Effects and double-quantum-filtered correlation spectroscopy in nuclear magnetic resonance (NMR) analyses of the A315E-mutant TDP-43 peptide indicate that it adopts an anti-parallel beta conformation. When added to cell cultures, the amyloidogenic TDP-43 peptides induce TDP-43 redistribution from the nucleus to the cytoplasm. Neuronal cultures in compartmentalized microfluidic chambers demonstrate that the TDP-43 peptides can be taken up by axons and induce axonotoxicity and neuronal death, thus recapitulating key neuropathological features of TDP-43 proteinopathies. Importantly, a single amino acid change in the amyloidogenic TDP-43 peptide that disrupts fibril formation also eliminates neurotoxicity, supporting that amyloidogenesis is critical for TDP-43 neurotoxicity. PMID- 25113751 TI - Trials of implantable monitoring devices in heart failure: which design is optimal? AB - Implantable monitoring devices have been developed to detect early evidence of heart failure (HF) decompensation, with the hypothesis that early detection might enable clinicians to commence therapy sooner than would otherwise be possible, and potentially to reduce the rate of hospitalization. In addition to the usual challenges inherent to device trials (such as the difficulty of double-blinding and potential for bias), studies of implantable monitoring devices present unique difficulties because they involve assessment of therapeutic end points for diagnostic devices. Problems include the lack of uniform approaches to treatment in study protocols for device alerts or out-of-range values, and the requirement of levels of evidence traditionally associated with therapeutic devices to establish effectiveness and safety. In this Review, the approaches used to deal with these issues are discussed, including the use of objective primary end points with blinded adjudication, identical duration of follow-up and number of encounters for patients in active monitoring and control groups, and treatment recommendations between groups that are consistent with international guidelines. Remote monitoring devices hold promise for reducing the rate of hospitalization among patients with HF. However, optimization of regulatory approaches and clinical trial design is needed to facilitate further evaluation of the effectiveness of combining health information technology and medical devices. PMID- 25113752 TI - Acute improvement of left ventricular relaxation as a predictor of volume reduction after cardiac resynchronization therapy: a pilot study assessing the value of left ventricular hemodynamic parameter. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) improves cardiac function, but CRT recipients with advanced heart failure (HF) do not always respond well. Because the best parameters for the prediction of CRT response are not established, we investigated whether improvement of invasive left ventricular (LV) hemodynamic diastolic parameters could identify CRT responders. METHODS: A total of 34 consecutive patients (age, 69 +/- 9 years; 70% men) who received CRT devices for HF were assessed as to whether acute invasive hemodynamic parameters with and without CRT function could predict LV volume responders. RESULTS: These patients demonstrated an improvement in LV dP/dtmax (11.1 +/- 11.7%), LV dP/dtmin (4.6 +/- 12.1%), and tau (3.7 +/- 11.6%) by biventricular pacing. Nineteen patients (55%) were classified as CRT responders, which was defined by a >15% decrease in LV end-systolic volume (ESV) at the 6-month follow-up evaluation. The area under the receiver operator characteristic curve to detect CRT volume response was 0.93 for the shortening of tau, which was superior to any other hemodynamic parameter. The multivariate analysis revealed that this improvement in tau was the strongest predictive factor for identifying CRT volume responders. Of note, the magnitude of tau shortening during biventricular pacing was significantly correlated with the reduction in LVESV at the 6-month follow-up evaluation. CONCLUSIONS: The extent of acute improvement in LV isovolumic relaxation time, as assessed by tau, was associated with favorable response to CRT. The assessment of invasive diastolic function could provide valuable information about CRT volume response. PMID- 25113750 TI - Global epidemiology of atrial fibrillation. AB - Atrial fibrillation (AF) is a major public health burden worldwide, and its prevalence is set to increase owing to widespread population ageing, especially in rapidly developing countries such as Brazil, China, India, and Indonesia. Despite the availability of epidemiological data on the prevalence of AF in North America and Western Europe, corresponding data are limited in Africa, Asia, and South America. Moreover, other observations suggest that the prevalence of AF might be underestimated-not only in low-income and middle-income countries, but also in their high-income counterparts. Future studies are required to provide precise estimations of the global AF burden, identify important risk factors in various regions worldwide, and take into consideration regional and ethnic variations in AF. Furthermore, in response to the increasing prevalence of AF, additional resources will need to be allocated globally for prevention and treatment of AF and its associated complications. In this Review, we discuss the available data on the global prevalence, risk factors, management, financial costs, and clinical burden of AF, and highlight the current worldwide inadequacy of its treatment. PMID- 25113754 TI - Retrospective propensity score matching and the selection of surgical procedures: how precise can a propensity estimate be? PMID- 25113755 TI - Reply to M. Honda et al. PMID- 25113753 TI - Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. AB - The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials. PMID- 25113757 TI - Targeting inhibitor of apoptosis proteins for cancer therapy: a double-edge sword? PMID- 25113756 TI - Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. AB - PURPOSE: LCL161 antagonizes the function of inhibitor of apoptosis proteins (IAPs), thereby promoting cancer cell death. This first-in-human dose-escalation study assessed the maximum-tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of LCL161 in patients with advanced solid tumors. A second part of the study assessed the relative bioavailability of a tablet versus solution formulation. PATIENTS AND METHODS: LCL161 was administered orally, once weekly, on a 21-day cycle to adult patients with advanced solid tumors by using an adaptive Bayesian logistic regression model with overdose control-guided dose escalation. RESULTS: Fifty-three patients received at least one dose of LCL161 (dose range, 10 to 3,000 mg). LCL161 was well tolerated at doses up to 1,800 mg. Cytokine release syndrome (CRS) was the only dose-limiting toxicity (in three [6%] of 53 patients) and was the most common grades 3 to 4 event (in five [9%] of 53 patients). Vomiting, nausea, asthenia/fatigue, and anorexia were common but not severe. Although the MTD was not formally determined, an 1,800-mg dose was selected in compliance with the protocol for additional study, given the dose limiting CRS at higher doses and pharmacodynamic activity at lower doses. LCL161 was rapidly absorbed, and exposure was generally increased with dose. The tablet formulation of LCL161 was better tolerated than the solution; tablet and solution formulations had similar exposures, and the solution was discontinued. No patient had an objective response. LCL161 induced degradation of cellular IAP1 protein in the blood, skin, and tumor and increased circulating cytokine levels. CONCLUSION: The 1,800-mg dose of LCL161, administered as a single agent once weekly, in tablet formulation is the recommended dose for additional study. This combined dose and formulation was well tolerated and had significant pharmacodynamic activity, which warrants additional investigation. PMID- 25113758 TI - Stereotactic body radiation therapy as a derivative of stereotactic radiosurgery: clinically independent but with enduring common themes. PMID- 25113759 TI - Value: a framework for radiation oncology. AB - In the current health care system, high costs without proportional improvements in quality or outcome have prompted widespread calls for change in how we deliver and pay for care. Value-based health care delivery models have been proposed. Multiple impediments exist to achieving value, including misaligned patient and provider incentives, information asymmetries, convoluted and opaque cost structures, and cultural attitudes toward cancer treatment. Radiation oncology as a specialty has recently become a focus of the value discussion. Escalating costs secondary to rapidly evolving technologies, safety breaches, and variable, nonstandardized structures and processes of delivering care have garnered attention. In response, we present a framework for the value discussion in radiation oncology and identify approaches for attaining value, including economic and structural models, process improvements, outcome measurement, and cost assessment. PMID- 25113760 TI - Patient-reported outcomes and survivorship in radiation oncology: overcoming the cons. AB - PURPOSE: Although patient-reported outcomes (PROs) have become a key component of clinical oncology trials, many challenges exist regarding their optimal application. The goal of this article is to methodically review these barriers and suggest strategies to overcome them. This review will primarily focus on radiation oncology examples, will address issues regarding the "why, how, and what" of PROs, and will provide strategies for difficult problems such as methods for reducing missing data. This review will also address cancer survivorship because it closely relates to PROs. METHODS: Key articles focusing on PROs, quality of life, and survivorship issues in oncology trials are highlighted, with an emphasis on radiation oncology clinical trials. Publications and Web sites of various governmental and regulatory agencies are also reviewed. RESULTS: The study of PROs in clinical oncology trials has become well established. There are guidelines provided by organizations such as the US Food and Drug Administration that clearly indicate the importance of and methodology for studying PROs. Clinical trials in oncology have repeatedly demonstrated the value of studying PROs and suggested ways to overcome some of the key challenges. The Radiation Therapy Oncology Group (RTOG) has led some of these efforts, and their contributions are highlighted. The current state of cancer survivorship guidelines is also discussed. CONCLUSION: The study of PROs presents significant benefits in understanding and treating toxicities and enhancing quality of life; however, challenges remain. Strategies are presented to overcome these hurdles, which will ultimately improve cancer survivorship. PMID- 25113761 TI - Emergence of stereotactic body radiation therapy and its impact on current and future clinical practice. AB - Stereotactic body radiation therapy (SBRT) is generally a tumor-ablative radiation modality using essential technologies capable of accurately and precisely damaging the target with a high dose while geometrically sparing innocent normal tissues. The intent, conduct, and tissue biology are all dramatically distinct from conventionally fractionated radiotherapy such that new understanding is required for its optimization. It is most practical, tolerable, and tumoricidal in its most potent form treating tumors in the lung and liver. However, it is increasingly being used for tumors adjacent to bowels and nervous tissue, albeit with somewhat less ablative potency. Its strengths include high rates of tumor eradication via a noninvasive, convenient outpatient treatment. Its weakness relates to the possibility of causing difficult-to-manage toxicity (eg, ulceration, stenosis, fibrosis, and even necrosis) that may occur considerably later after treatment, particularly in the vicinity of the body's many tubular structures (eg, organ hila, bowel). However, clinical trials in a variety of organs and sites have shown SBRT to result in good outcomes in properly selected patients. Given its short course, lack of need for recovery, and favorable overall toxicity profile, there is great hope that SBRT will find a prominent place in the treatment of metastatic cancer as a consolidative partner with systemic therapy. With considerable published experience, available required technologies and training, and many patients in need of local therapy, SBRT has found a place in the routine cancer-fighting arsenal. PMID- 25113763 TI - Psychosexual functioning among adult female survivors of childhood cancer: a report from the childhood cancer survivor study. AB - PURPOSE: Childhood cancer survivors may be at risk for impaired psychosexual functioning as a direct result of their cancer or its treatments, psychosocial difficulties, and/or diminished quality of life. PATIENTS AND METHODS: Two thousand one hundred seventy-eight female adult survivors of childhood cancer and 408 female siblings from the Childhood Cancer Survivor Study (CCSS) completed a self-report questionnaire about their psychosexual functioning and quality of life. On average, participants were age 29 years (range, 18 to 51 years) at the time of the survey, had been diagnosed with cancer at a median age of 8.5 years (range, 0 to 20) and were most commonly diagnosed with leukemia (33.2%) and Hodgkin lymphoma (15.4%). RESULTS: Multivariable analyses suggested that after controlling for sociodemographic differences, survivors reported significantly lower sexual functioning (mean difference [MnD], -0.2; P = .01), lower sexual interest (MnD, -0.2; P < .01), lower sexual desire (MnD, -0.3; P < .01), lower sexual arousal (MnD, -0.3; P < .01), lower sexual satisfaction (MnD, -0.2; P = .01), and lower sexual activity (MnD, -0.1; P = .02) compared with siblings. Risk factors for poorer psychosexual functioning among survivors included older age at assessment, ovarian failure at a younger age, treatment with cranial radiation, and cancer diagnosis during adolescence. CONCLUSION: Decreased sexual functioning among female survivors of childhood cancers seems to be unrelated to emotional factors and is likely to be an underaddressed issue. Several risk factors among survivors have been identified that assist in defining high-risk subgroups who may benefit from targeted screening and interventions. PMID- 25113764 TI - Frontiers in radiotherapy for early-stage invasive breast cancer. AB - The development of breast-conserving treatment for early-stage breast cancer is one of the most important success stories in radiation oncology in the latter half of the twentieth century. Lumpectomy followed by radiotherapy provides an appealing alternative to mastectomy for many women. In recent years, there has been a shift in clinical investigational focus toward refinements in the methods of delivering adjuvant radiotherapy that provide shorter, more convenient schedules of external-beam radiotherapy and interstitial treatment. Expedited courses of whole-breast treatment have been demonstrated to be equivalent to traditional lengthier courses in terms of tumor control and cosmetic outcome and to provide an opportunity for cost efficiencies. PMID- 25113762 TI - Cranial stereotactic radiosurgery: current status of the initial paradigm shifter. AB - The concept of stereotactic radiosurgery (SRS) was first described by Lars Leksell in 1951. It was proposed as a noninvasive alternative to open neurosurgical approaches to manage a variety of conditions. In the following decades, SRS emerged as a unique discipline involving a collegial partnership among neurosurgeons, radiation oncologists, and medical physicists. SRS relies on the precisely guided delivery of high-dose ionizing radiation to an intracranial target. The focused convergence of multiple beams yields a potent therapeutic effect on the target and a steep dose fall-off to surrounding structures, thereby minimizing the risk of collateral damage. SRS is typically administered in a single session but can be given in as many as five sessions or fractions. By providing an ablative effect noninvasively, SRS has altered the treatment paradigms for benign and malignant intracranial tumors, functional disorders, and vascular malformations. Literature on extensive intracranial radiosurgery has unequivocally demonstrated the favorable benefit-to-risk profile that SRS affords for appropriately selected patients. In a departure from conventional radiotherapeutic strategies, radiosurgical principles have recently been extended to extracranial indications such as lung, spine, and liver tumors. The paradigm shift resulting from radiosurgery continues to alter the landscape of related fields. PMID- 25113766 TI - Enhancing the efficacy of radiation therapy: premises, promises, and practicality. PMID- 25113767 TI - Impact of informative censoring on the Kaplan-Meier estimate of progression-free survival in phase II clinical trials. AB - Informative censoring in a progression-free survival (PFS) analysis arises when patients are censored for initiation of an effective anticancer treatment before the protocol-defined progression, and these patients are at a different risk for treatment failure than those who continue on therapy. This may cause bias in the estimated PFS when using the Kaplan-Meier method for analysis. Although there are several articles that discuss this issue from a theoretical perspective or in randomized phase III studies, there are little data to demonstrate the magnitude of the bias on the estimated quantities from a phase II trial. This article describes the issues by using two oncology phase II trials as examples, evaluates the impact of the bias using simulations, and provides recommendations. The two trials were selected because they demonstrate two different reasons for censoring. Simulations show that the magnitude of the bias depends primarily on the proportion of patients who are informatively censored and secondarily on the hazard ratio between the group of patients who remain on study and the group of patients who are informatively censored. Recommendations include using an alternative end point, which includes inadequate response and initial signs of clinical progression as treatment failure, and a competing risk analysis for studies in which competing events preclude or modify the probability of observing the primary event of interest. If informative censoring cannot be avoided, then all patients should be observed until progression, and sensitivity analyses should be used as appropriate. PMID- 25113765 TI - Radical irradiation of extracranial oligometastases. AB - Advances in radiotherapy planning and delivery have been used to treat patients with limited metastatic disease. With these techniques, high rates of treated metastasis control and low toxicity have been reported. Some patients have long disease-free intervals after radiotherapy similar to those seen after surgical resection. Ongoing studies will determine the benefit of these irradiation techniques to treat limited metastases, identify appropriate candidates, and assist in integrating these treatments into management strategies for specific diseases. PMID- 25113768 TI - Molecular radiobiology: the state of the art. AB - Traditional cytotoxic agents used in cancer therapy were initially discovered based on their ability to kill rapidly dividing cells. The targets of these early generation agents were typically one or more aspects of DNA synthesis or mitosis. Thus, dose-limiting toxicities commonly associated with these agents include GI dysfunction, immunosuppression, and other consequences of injury to normal tissues in which cells are replicating under normal physiologic conditions. Although many of these agents still play an important role in cancer therapy when given concurrently with radiation therapy, the major thrust of radiobiology research in the last two decades has focused on discovering tumor-specific traits that might be exploited for more selective targeting that would enhance the efficacy of radiotherapy with less normal tissue toxicity. These newer generation molecular targeted therapies interfere with the growth of tumor cells by inhibiting genes and their protein products that are needed specifically by the tumor for survival and expansion. These agents can be complementary to radiotherapy, a spatially targeted agent. Although there have been extraordinary technical advances in radiotherapy in recent years, we are reaching the limits of improvements that radiotherapy delivery technology can bring and need different approaches. This review will highlight promising new tumor biology-based targets and other novel strategies to reduce normal tissue injury, increase tumor control, and expand the use of radiotherapy to treat widespread metastatic disease. PMID- 25113769 TI - Nanotechnology in radiation oncology. AB - Nanotechnology, the manipulation of matter on atomic and molecular scales, is a relatively new branch of science. It has already made a significant impact on clinical medicine, especially in oncology. Nanomaterial has several characteristics that are ideal for oncology applications, including preferential accumulation in tumors, low distribution in normal tissues, biodistribution, pharmacokinetics, and clearance, that differ from those of small molecules. Because these properties are also well suited for applications in radiation oncology, nanomaterials have been used in many different areas of radiation oncology for imaging and treatment planning, as well as for radiosensitization to improve the therapeutic ratio. In this article, we review the unique properties of nanomaterials that are favorable for oncology applications and examine the various applications of nanotechnology in radiation oncology. We also discuss the future directions of nanotechnology within the context of radiation oncology. PMID- 25113770 TI - Interaction of radiation therapy with molecular targeted agents. AB - The development of molecular targeted therapeutics in oncology builds on many years of scientific investigation into the cellular mechanics of malignant transformation and progression. The past two decades have brought an accelerating pace to the clinical investigation of new molecular targeted agents, particularly in the setting of metastatic disease. The integration of molecular targeted agents into phase III clinical trial design has lagged in the curative treatment setting, particularly in combination with established therapeutic modalities such as radiation. In this review, we discuss the interaction of radiation and molecular targeted therapeutics. The dynamics of cellular and tumor response to radiation offer unique opportunities for beneficial interplay with molecular targeted agents that may go unrecognized with conventional screening and monotherapy clinical testing of novel agents. By using epidermal growth factor receptor (EGFR) as a primary example, we discuss recent clinical studies that illustrate the potential synergy of molecular targeted agents with radiation and highlight the clinical value of such interactions. For various molecular targeted agents, their greatest clinical impact may rest in combination with radiation, and efforts to facilitate systematic investigation of this approach appear highly warranted. PMID- 25113774 TI - Radiation oncology: a snapshot in time, 2014. PMID- 25113772 TI - Promise and pitfalls of heavy-particle therapy. AB - Proton beam therapy, the most common form of heavy-particle radiation therapy, is not a new invention, but it has gained considerable public attention because of the high cost of installing and operating the rapidly increasing number of treatment centers. This article reviews the physical properties of proton beam therapy and focuses on the up-to-date clinical evidence comparing proton beam therapy with the more standard and widely available radiation therapy treatment alternatives. In a cost-conscious era of health care, the hypothetical benefits of proton beam therapy will have to be supported by demonstrable clinical gains. Proton beam therapy represents, through its scale and its cost, a battleground for the policy debate around managing expensive technology in modern medicine. PMID- 25113773 TI - Role of radiation therapy in palliative care of the patient with cancer. AB - Radiotherapy is a successful, time-efficient, well-tolerated, and cost-effective intervention that is crucial for the appropriate delivery of palliative oncology care. The distinction between curative and palliative goals is blurred in many patients with cancer, requiring that treatments be chosen on the basis of factors related to the patient (ie, poor performance status, advanced age, significant weight loss, severe comorbid disease), the cancer (ie, metastatic disease, aggressive histology), or the treatment (ie, poor response to systemic therapy, previous radiotherapy). Goals may include symptom relief at the site of primary tumor or from metastatic lesions. Attention to a patient's discomfort and transportation limitations requires hypofractionated courses, when feasible. Innovative approaches include rapid response palliative care clinics as well as the formation of palliative radiotherapy specialty services in academic centers. Guidelines are providing better definitions of appropriate palliative radiotherapy interventions, and bone metastases fractionation has become the first radiotherapy quality measure accepted by the National Quality Forum. Further advances in the palliative radiation oncology subspecialty will require integration of education and training between the radiotherapy and palliative care specialties. PMID- 25113775 TI - Simultaneous determination of nine lignans from Schisandra chinensis extract using ultra-performance liquid chromatography with tandem mass spectrometry in rat plasma, urine, and gastrointestinal tract samples: application to the pharmacokinetic study of Schisandra chinensis. AB - The fruit of Schisandra chinensis is a well-known herbal medicine and dietary supplement due to a variety of biological activities including antihepatotoxic and antihyperlipidemic activities. However, the simultaneous validation methodology and pharmacokinetic investigation of nine lignans of S. chinensis extract in biological samples have not been proved yet. Thus, the present study was undertaken to develop the proper sample preparation method and simultaneous analytical method of schisandrol A, gomisin J, schisandrol B, tigloylgomisin H, angeloylgomisin H, schisandrin A, schisandrin B, gomisin N, and schisandrin C in the hexane-soluble extract of S. chinensis to apply for the pharmacokinetic study in rats. All intra- and interprecisions of nine lignans were below 13.7% and accuracies were 85.1-115% and it is enough to evaluate the pharmacokinetic parameters after both intravenous and oral administration of hexane-soluble extract of S. chinensis to rats. PMID- 25113776 TI - Electrical resistivity behaviors of liquid Pb-Sn binary alloy in the presence of ultrasonic field. AB - Electrical resistivity behaviors of liquid Pb-Sn alloys have been investigated in the presence of ultrasonic field. The process demonstrated significantly that electrical resistivity could reveal the precise influence caused by ultrasound. Details revealed by applying the resistivity measuring approach to the liquid Pb Sn alloy show that the short ordered structures in the liquid could be modified by ultrasonic irradiation, and the resistivity approach could have application value in the ultrasonic irradiation process on the specific liquid metals and alloys. PMID- 25113771 TI - Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. AB - PURPOSE: Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response-adapted treatment guided by early interim positron emission tomography (PET)-computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely. METHODS: An imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma. RESULTS: A working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods. CONCLUSION: This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials. PMID- 25113777 TI - N-methyl-trimethylacetamide in thin films displays infrared spectra of pi helices, with visible static and dynamic growth phases, and then a beta-sheet. AB - The simplest (minimal) peptide model is HCONHCH3. An increase in the pi-helix content with increased substitution in the acyl portion suggested the examination of N-methyl-trimethylacetamide) (NMT). NMT displays spectra, in which there is evolution of a set of helices defined by their amide I maxima near 1686 (3(10)), 1655 (first pi), and, most importantly, at 1637 cm(-1) (pi). Expanded thin-film infrared spectroscopy (XTFIS) shows pauses or slow stages, which are identified as static phases followed by dynamic phases with the incremental gain or loss of a helix turn. In addition, absorbance at 1637 cm(-1) suddenly increases at 82.1 s (30% over 0.3 s), indicating a phase change and crystallization of the pi-helix, along with a coincidental decrease in the absorbance for the first pi-helix. A sharp peak occurs at the maximum of the phase change at 82.5 s, representing a pure NMT pi-helix. The spectra then undergo a decreasing general absorption loss over 150 s, with the pi-helix evolving further to an antiparallel beta-sheet fragment. The spectral quality arises from the immobilization of polar molecules on polar surfaces. The crystal structure is that of an antiparallel beta-sheet. PMID- 25113778 TI - Co-inheritance of the rare beta hemoglobin variants Hb Yaounde, Hb Gorwihl and Hb City of Hope with other alterations in globin genes: impact in genetic counseling. AB - PURPOSE: Nearly 1183 different molecular defects of the globin genes leading to hemoglobin variants have been identified (http://globin.bx.psu.edu) over the past decades. The purpose of this study was to report three cases, never described in the literature, of co-inheritance of three beta hemoglobin variants with other alterations in globin genes and to evaluate the clinical significance to conduct an appropriate genetic counseling. PATIENTS AND METHODS: We report the molecular study performed in three probands and their families, sampling during the screening program conducted at the Laboratory for Molecular Prenatal Diagnosis of Hemoglobinopathies at Villa Sofia-Cervello Hospital in Palermo, Italy. RESULTS: This work allowed us to describe the co-inheritance of three rare beta hemoglobin variants with other alterations in globin genes: the beta hemoglobin variant Hb Yaounde [beta134(H12)Val>Ala], found for the first time in combination with alphaalphaalpha(anti3.7) arrangement, and the beta hemoglobin variants Hb Gorwihl [beta5(A2)Pro>Ala] and Hb City of Hope [beta69(E13)Gly>Ser], found both in association with beta(0) -thalassemia. CONCLUSION: The present work emphasizes the importance of a careful evaluation of the hematological data, especially in cases of atypical hematological parameters, to carry out an adequate and complete molecular study and to formulate an appropriate genetic counseling for couples at risk. PMID- 25113779 TI - Scientific and technical data sharing: a trading perspective. AB - It is arguably a precept that the open sharing of data maximises the scientific utility of the research that generated that data. Indeed, progress depends on individual scientists being able to build on the results produced by others. The means to facilitate sharing undoubtedly exist, but various studies have identified reluctance among researchers to share information with their peers, at least until the professional priorities of the original researchers have been accommodated. With a view to encouraging less inhibited collaboration, we appraise the processes of data exchange from the perspective of a trading environment and consider how data exchanges might promote (or perhaps hinder) collaboration in data-rich scientific research disciplines and how such an exchange might be set up. We suggest an exchange with trusted brokers (akin to the commodity markets) as a way to overcome the challenges of the current environment. We conclude by encouraging the scientific and technical community to debate the merits of a trading perspective on data sharing and exchange. PMID- 25113782 TI - Doctor, what does my knee arthroplasty weigh? AB - The aim of this study was to compare the weight of the total knee arthroplasty (TKA) implants and the weight of the natural knee. A prospective study was conducted with two different brands of cemented primary TKA. During the procedure, we collected the removed bone, soft tissues and the post-implantation cement and weighed them all separately at the end. In both groups, the implants plus cement were significantly heavier than the removed bone and soft tissues. The average weight gained was 266.7 +/- 35.1 g for group 1 and 279.1 +/- 48.7 g for group 2. This significant local weight gained after TKA is a new parameter that should be taken into account for further studies and when creating new implants. PMID- 25113781 TI - Cardiorespiratory responses to 6-minute walk test in interstitial lung disease: not always a submaximal test. AB - BACKGROUND: The 6-minute walk test (6 MWT) is used to measure exercise capacity and assess prognosis in interstitial lung disease (ILD). Although the 6 MWT is usually considered to be a test of submaximal exercise capacity in ILD, the physiological load imposed by this test is not well described and 6 MWT outcomes are poorly understood. This study aimed to compare cardiorespiratory responses to 6 MWT and cardiopulmonary exercise test (CPET) in people with ILD. METHODS: 47 participants with ILD (27 idiopathic pulmonary fibrosis (IPF), mean age 71 (SD 12) years, diffusing capacity for carbon monoxide (TLCO) 49(15) %predicted) undertook CPET and 6 MWT on the same day in random order. Oxygen uptake (VO(2)), ventilation (VE) and carbon dioxide production (VCO2) were assessed during each test using a portable metabolic cart. RESULTS: The VO(2)peak during the 6 MWT was lower than during CPET (1.17(0.27) vs 1.30(0.37) L.min-1, p = 0.001), representing an average of 94% (range 62-135%) of CPET VO(2)peak. Achieving a higher percentage of CPET VO(2)peak on 6 MWT was associated with lower TLCO %predicted (r = -0.43, p = 0.003) and more desaturation during walking (r = 0.46, p = 0.01). The VEpeak and VCO(2)peak were significantly lower during 6 MWT than CPET (p < 0.05). However, participants desaturated more during the 6 MWT (86(6)% vs 89(4)%, p < 0.001). The degree of desaturation was not affected by the percent of peak VO2 achieved during the 6 MWT. Responses were similar in the subgroup with IPF. CONCLUSIONS: On average, the 6 MWT elicits a high but submaximal oxygen uptake in people with ILD. However the physiological load varies between individuals, with higher peak VO2 in those with more severe disease that may match or exceed that achieved on CPET. The 6 MWT is not always a test of submaximal exercise capacity in people with ILD. PMID- 25113783 TI - Patient-related predictors of treatment failure after primary total knee arthroplasty for osteoarthritis. AB - The aim was to identify patient-related predictors of treatment failure after primary total knee arthroplasty for osteoarthritis. Treatment failure included surgical revision or clinical failure, which was defined by less than 70 in any score of the Knee Society. Prospective follow-up was performed in 412 consecutive patients with a minimum of 5 years. Multivariate logistic regression analysis revealed that higher Charlson index, worse preoperative Knee Society function, and Western Ontario McMaster University pain component were significantly associated with treatment failure. This study identified clinically important patient-related predictors of treatment failure after TKA, which may be useful preoperatively in identifying patients with risk of failure. PMID- 25113784 TI - Prevalence and predictors of post-operative coronal alignment outliers and their association with the functional outcomes in navigated total knee arthroplasty. AB - We aimed to determine the prevalence and predictors for being an outlier after navigated TKA and asked whether navigated TKAs with perfect coronal alignment have better functional outcomes than those without it. Alignment was measured in 124 patients (191 knees) with navigated TKAs who were available for 1year functional outcome assessment. The outcomes were compared among the 3 subgroups divided by the deviation of mechanical axis from neutral (0 degrees ): the perfect, 0 degrees or within 1 degrees ; the acceptable, 1 degrees -3 degrees ; and the outlier, beyond 3 degrees . The prevalence of outliers was 20.4%, and the severity of preoperative varus deformity was the strongest predictor. Accuracy of coronal alignment in radiographs did not correlate consistently with functional outcomes. PMID- 25113785 TI - Cell blocks in cytopathology: a review of preparative methods, utility in diagnosis and role in ancillary studies. AB - The cell block (CB) is a routine procedure in cytopathology that has gained importance because of its pivotal role in diagnosis and ancillary studies. There is no precise review in the published literature that deals with the various methods of preparation of CB, its utility in diagnosis, immunocytochemistry (ICC) or molecular testing, and its drawbacks. An extensive literature search on CB in cytology using internet search engines was performed for this review employing the following keywords: cell block, cytoblock, cytology, cytopathology, methods, preparation, fixatives, diagnostic yield, ancillary and molecular studies. Ever since its introduction more than a century ago, the CB technique has undergone numerous modifications to improve the quality of the procedure; however, the overall principle remains the same in each method. CBs can be prepared from virtually all varieties of cytological samples. In today's era of personalized medicine, cytological specimens, including CBs, augment the utility of cytological samples in analysing the molecular alterations as effectively as surgical biopsies or resection specimens. With the availability of molecular targeted therapy for many cancers, a large number of recent studies have used cytological material or CBs for molecular characterization. The various techniques of CB preparation with different fixatives, their advantages and limitations, and issues of diagnostic yield are discussed in this review. PMID- 25113786 TI - Comparative effects of biological and chemical dispersants on the bioavailability and toxicity of crude oil to early life stages of marine medaka (Oryzias melastigma). AB - The authors assessed the bioavailability and chronic toxicity of water accommodated fractions of crude oil (WAFs) and 2 dispersants plus dispersed crude oil (chemical dispersant + crude oil [CE-WAF] and biological dispersant + crude oil [BE-WAF]) on the early life stages of marine medaka, Oryzias melastigma. The results showed that the addition of the 2 dispersants caused a 3- and 4-fold increase in concentrations of summed priority polycyclic aromatic hydrocarbons (PAHs) and high-molecular-weight PAHs with 3 or more benzene rings. The chemical and biological dispersants increased the bioavailability (as measured by ethoxyresorufin-O-dethylase activity) of crude oil 6-fold and 3-fold, respectively. Based on nominal concentrations, chronic toxicity (as measured by deformity) in WAFs exhibited a 10-fold increase in CE-WAF and a 3-fold increase in BE-WAF, respectively. When total petroleum hydrocarbon was measured, the differences between WAF and CE-WAF treatments disappeared, and CE-WAF was approximately 10 times more toxic than BE-WAF. Compared with the chemical dispersant, the biological dispersant possibly modified the toxicity of oil hydrocarbons because of the increase in the proportion of 2- and 3-ringed PAHs in water. The chemical and biological dispersants enhanced short-term bioaccumulation and toxicity, through different mechanisms. These properties should be considered in addition to their efficacy in degrading oil when oil spill management strategies are selected. PMID- 25113787 TI - Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease. PMID- 25113788 TI - Reply: Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease. PMID- 25113789 TI - The evolution of primary progressive apraxia of speech. AB - Primary progressive apraxia of speech is a recently described neurodegenerative disorder in which patients present with an isolated apraxia of speech and show focal degeneration of superior premotor cortex. Little is known about how these individuals progress over time, making it difficult to provide prognostic estimates. Thirteen subjects with primary progressive apraxia of speech underwent two serial comprehensive clinical and neuroimaging evaluations 2.4 years apart [median age of onset = 67 years (range: 49-76), seven females]. All underwent detailed speech and language, neurological and neuropsychological assessments, and magnetic resonance imaging, diffusion tensor imaging and (18)F fluorodeoxyglucose positron emission tomography at both baseline and follow-up. Rates of change of whole brain, ventricle, and midbrain volumes were calculated using the boundary-shift integral and atlas-based parcellation, and rates of regional grey matter atrophy were assessed using tensor-based morphometry. White matter tract degeneration was assessed on diffusion-tensor imaging at each time point. Patterns of hypometabolism were assessed at the single subject-level. Neuroimaging findings were compared with a cohort of 20 age, gender, and scan interval matched healthy controls. All subjects developed extrapyramidal signs. In eight subjects the apraxia of speech remained the predominant feature. In the other five there was a striking progression of symptoms that had evolved into a progressive supranuclear palsy-like syndrome; they showed a combination of severe parkinsonism, near mutism, dysphagia with choking, vertical supranuclear gaze palsy or slowing, balance difficulties with falls and urinary incontinence, and one was wheelchair bound. Rates of whole brain atrophy (1.5% per year; controls = 0.4% per year), ventricular expansion (8.0% per year; controls = 3.3% per year) and midbrain atrophy (1.5% per year; controls = 0.1% per year) were elevated (P <= 0.001) in all 13, compared to controls. Increased rates of brain atrophy over time were observed throughout the premotor cortex, as well as prefrontal cortex, motor cortex, basal ganglia and midbrain, while white matter tract degeneration spread into the splenium of the corpus callosum and motor cortex white matter. Hypometabolism progressed over time in almost all subjects. These findings demonstrate that some subjects with primary progressive apraxia of speech will rapidly evolve and develop a devastating progressive supranuclear palsy-like syndrome ~ 5 years after onset, perhaps related to progressive involvement of neocortex, basal ganglia and midbrain. These findings help improve our understanding of primary progressive apraxia of speech and provide some important prognostic guidelines. PMID- 25113791 TI - A novel CDC73 gene mutation in an Italian family with hyperparathyroidism-jaw tumour (HPT-JT) syndrome. AB - PURPOSE: The CDC73 gene, encoding parafibromin, has been identified as a tumour suppressor gene both in hyperparathyroidism-jaw tumour (HPT-JT) syndrome and in sporadic parathyroid carcinoma. While the vast majority of CDC73 mutations affect the N-terminus or the central core of the encoded protein, as yet few mutations have been reported affecting the C-terminus. Here, we report a case (Caucasian female, 28 years) with an invasive ossifying fibroma of the left mandible and hyperparathyroidism (sCa = 16 mg/dl, PTH = 660 pg/mL) due to a parathyroid lesion of 20 mm, hystologically diagnosed as carcinoma. METHODS: The whole CDC73 gene was screened for the presence of mutations by Sanger sequencing. Immunohistochemistry, in vitro functional assays, Western blotting, MTT assays and in-silico modelling were performed to assess the effect of the detected mutation. RESULTS: Sequence analysis of the CDC73 gene in the proband revealed the presence of a novel deletion affecting the C-terminus of the encoded protein (c.1379delT/p.L460Lfs*18). Clinical and genetic analyses of the available relatives led to the identification of three additional carriers, one of whom was also affected by a parathyroid lesion. Immunohistochemistry, Western blotting, MTT and in-silico modelling assays revealed that the deletion leads to down regulation of the mutated protein, most likely through a proteasome-mediated pathway. We also found that the deletion may cause a conformational change in the C-terminus of the protein, possibly affecting its interaction with partner proteins. Finally, we found that the mutant protein enhances cellular growth. CONCLUSIONS: We report a novel mutation in the CDC73 gene that may underlie HPT JT syndrome. This mutation appears to affect the C-terminal moiety of the encoded protein, which is thought to interact with other protein partners. The identification of these partners may be instrumental for our understanding of the CDC73-associated phenotype. PMID- 25113792 TI - Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice. AB - BACKGROUND: The aim of this study was to probe cardiac complications, including heart-rate control, in a mouse model of type-2 diabetes. Heart-rate development in diabetic patients is not straight forward: In general, patients with diabetes have faster heart rates compared to non-diabetic individuals, yet diabetic patients are frequently found among patients treated for slow heart rates. Hence, we hypothesized that sinoatrial node (SAN) dysfunction could contribute to our understanding of the mechanism behind this conundrum and the consequences thereof. METHODS: Cardiac hemodynamic and electrophysiological characteristics were investigated in diabetic db/db and control db/+ mice. RESULTS: We found improved contractile function and impaired filling dynamics of the heart in db/db mice, relative to db/+ controls. Electrophysiologically, we observed comparable heart rates in the two mouse groups, but SAN recovery time was prolonged in diabetic mice. Adrenoreceptor stimulation increased heart rate in all mice and elicited cardiac arrhythmias in db/db mice only. The arrhythmias emanated from the SAN and were characterized by large RR fluctuations. Moreover, nerve density was reduced in the SAN region. CONCLUSIONS: Enhanced systolic function and reduced diastolic function indicates early ventricular remodeling in obese and diabetic mice. They have SAN dysfunction, and adrenoreceptor stimulation triggers cardiac arrhythmia originating in the SAN. Thus, dysfunction of the intrinsic cardiac pacemaker and remodeling of the autonomic nervous system may conspire to increase cardiac mortality in diabetic patients. PMID- 25113795 TI - Contactless conductivity detection for analytical techniques-developments from 2012 to 2014. AB - The review covers the progress of capacitively coupled contactless conductivity detection over the 2 years leading up to mid-2014. During this period many new applications for conventional CE as well as for microchip separation devices have been reported; prominent areas have been clinical, pharmaceutical, forensic, and food analyses. Further progress has been made in the development of field portable instrumentation based on CE with contactless conductivity detection. Several reports concern the combination with sample pretreatment techniques, in particular electrodriven extractions. Accounts of arrays of contactless conductivity detectors have appeared, which have been created for quite different tasks requiring spatially resolved information. The trend of the use of contactless conductivity measurements for applications other than CE has continued. PMID- 25113794 TI - 7T T2*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease. AB - The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(*)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p <= 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. PMID- 25113796 TI - Beta-blockers in cirrhosis and refractory ascites: a retrospective cohort study and review of the literature. AB - OBJECTIVE: It is currently discussed if beta-blockers exert harmful effects and increase mortality in patients with cirrhosis and refractory ascites. In this study, we provide an overview of the available literature in this field in combination with a retrospective analysis of 61 patients with cirrhosis and refractory ascites in a tertiary unit. MATERIAL AND METHODS: We performed a systematic search of literature in May 2014. In addition, 61 patients with cirrhosis and ascites were identified and followed from development of refractory ascites until death or end of follow-up. RESULTS: Fourteen trials (9 trials on propranolol, 1 case-control study and 4 retrospective analyses) were identified. One trial suggested an increased mortality in patients treated with beta-blockers and refractory ascites. The results of the remaining trials were inconclusive. No increase in mortality among beta-blocker-treated patients was found in the present retrospective analysis. CONCLUSIONS: Treatment with beta-blockers may increase mortality in patients with cirrhosis and refractory ascites. However, the current evidence is sparse and high-quality studies are warranted to clarify the matter. PMID- 25113790 TI - Long non-coding RNAs in cancer: implications for personalized therapy. AB - Long non-coding RNAs (lncRNAs, pseudogenes and circRNAs) have recently come into light as powerful players in cancer pathogenesis and it is becoming increasingly clear that they have the potential of greatly contributing to the spread and success of personalized cancer medicine. In this concise review, we briefly introduce these three classes of long non-coding RNAs. We then discuss their applications as diagnostic and prognostic biomarkers. Finally, we describe their appeal as targets and as drugs, while pointing out the limitations that still lie ahead of their definitive entry into clinical practice. PMID- 25113797 TI - Impact of implementation of the Surgical Care Improvement Project and future strategies for improving quality in surgery. AB - BACKGROUND: We present a comprehensive systematic review of the effect of Surgical Care Improvement Project (SCIP) measures on surgical site infections (SSIs) as related to SCIP compliance. DATA SOURCES: A systematic review of the peer-reviewed literature was performed on PubMed, Medline, and Cochrane database group using their own search engines. Keywords used were Surgical Care Improvement Project (SCIP), adherence, compliance, surgical site infection (SSI), infection bundle, antibiotics, perioperative antibiotics, and combinations thereof. Furthermore, reference lists of selected articles were cross-searched for additional literature. Papers published from January 1, 1998 to January 1, 2014 were included. RESULTS: A comprehensive analysis of these data demonstrated an 18% decrease in the odds of developing SSI and a cumulative 4% decrease in SSI. The largest increases in compliance for individual SCIP measures were reported between 2004 and 2006. However, compliance with multiple measures simultaneously had the sharpest increase between 2006 and 2009 without a definitive asymptote ascertained from the current data. CONCLUSIONS: These results represent some positive progress toward the SCIP task force's 2006 goal of a 25% decrease in SSI by 2010. Suggestions for improved future papers in this area were also added. PMID- 25113793 TI - Relationships between default-mode network connectivity, medial temporal lobe structure, and age-related memory deficits. AB - Advanced aging negatively impacts memory performance. Brain aging has been associated with shrinkage in medial temporal lobe structures essential for memory -including hippocampus and entorhinal cortex--and with deficits in default-mode network connectivity. Yet, whether and how these imaging markers are relevant to age-related memory deficits remains a topic of debate. Using a sample of 182 older (age 74.6 +/- 6.2 years) and 66 young (age 22.2 +/- 3.6 years) participants, this study examined relationships among memory performance, hippocampus volume, entorhinal cortex thickness, and default-mode network connectivity across aging. All imaging markers and memory were significantly different between young and older groups. Each imaging marker significantly mediated the relationship between age and memory performance and collectively accounted for most of the variance in age-related memory performance. Within older participants, default-mode connectivity and hippocampus volume were independently associated with memory. Structural equation modeling of cross sectional data within older participants suggest that entorhinal thinning may occur before reduced default-mode connectivity and hippocampal volume loss, which in turn lead to deficits in memory performance. PMID- 25113799 TI - Embryonic aneuploidy: overcoming molecular genetics challenges improves outcomes and changes practice patterns. AB - Since its inception, in vitro fertilization (IVF) has pursued molecular technology to improve patient outcomes, leading to enhanced methods of embryo selection. Comprehensive chromosomal screening (CCS) is a powerful tool that decreases maternal and neonatal morbidity due to multiple gestations by allowing the transfer of fewer embryos while maintaining success rates. To optimize this genetic test, physiological principles limiting the timing and type of cells to be removed had to be realized. Molecular barriers involved in genome amplification and ensuring the accuracy and validity of the CCS platform required a multistep approach to ensure that this technology was not used prematurely. Only after ensuring that the potential for harm was minimized and benefit maximized could clinicians use this technology to improve patient care. PMID- 25113800 TI - Evaluation of tumor response to cytokine-induced killer cells therapy in malignant solid tumors. AB - CIK cells therapy has been evaluated as an adoptive cell immunotherapy for cancer patients, but there still have not been any standardized systems for evaluating the antitumor efficacy yet. The WHO and RECIST criteria have already been established for a few years but not sufficient to fully characterize the activity of immunotherapy. Based on these two criteria, the irRC was proposed for evaluating the efficacy of immunotherapy. A variety of bioassays for immune monitoring including the specific and non-specific methods, have been established. We recommend detect levels of various immunocytes, immune molecules and soluble molecules to find the correlations among them and clinicopathological characteristics to establish criteria for immunological classification. We also recommend a paradigm shift for the oncologists in the evaluation of immune therapies to ensure assessment of activity based on clinically relevant criteria and time points. PMID- 25113802 TI - Carcinoid tumor of the minor duodenal papilla: a rare entity in elderly individuals. PMID- 25113803 TI - High-capacity anode materials for sodium-ion batteries. AB - Na-ion batteries are an attractive alternative to Li-ion batteries for large scale energy storage systems because of their low cost and the abundant Na resources. This Review provides a comprehensive overview of selected anode materials with high reversible capacities that can increase the energy density of Na-ion batteries. Moreover, we discuss the reaction and failure mechanisms of those anode materials with a view to suggesting promising strategies for improving their electrochemical performance. PMID- 25113805 TI - Different regions of bovine deep digital flexor tendon exhibit distinct elastic, but not viscous, mechanical properties under both compression and shear loading. AB - Tendons in different locations function in unique, and at times complex, in vivo loading environments. Specifically, some tendons are subjected to compression, shear and/or torsion in addition to tensile loading, which play an important role in regulating tendon properties. To date, there have been few studies evaluating tendon mechanics when loaded in compression and shear, which are particularly relevant for understanding tendon regions that experience such non-tensile loading during normal physiologic function. The objective of this study was to evaluate mechanical responses of different regions of bovine deep digital flexor tendons (DDFT) under compressive and shear loading, and correlate structural characteristics to functional mechanical properties. Distal and proximal regions of DDFT were evaluated in a custom-made loading system via three-step incremental stress-relaxation tests. A two-relaxation-time solid linear model was used to describe the viscoelastic response. Results showed large differences in the elastic behavior between regions: distal region stresses were 4-5 times larger than proximal region stresses during compression and 2-3 times larger during shear. Surprisingly, the viscous (i.e., relaxation) behavior was not different between regions for either compression or shear. Histological analysis showed that collagen and proteoglycan in the distal region distributed differently from the proximal region. Results demonstrate mechanical differences between two regions of DDFT under compression and shear loading, which are attributed to variations of composition and microstructural organization. These findings deepen our understanding of structure-function relationships of tendon, particularly for tissues adapted to supporting combinations of tension, compression, and shear in physiological loading environments. PMID- 25113804 TI - Docetaxel followed by abiraterone in metastatic castration-resistant prostate cancer: efficacy and predictive parameters in a large single center cohort. AB - PURPOSE: To report the outcome and course of disease in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel followed by abiraterone acetate in a single center. METHODS: In this retrospective observational study, we reviewed the course of disease of all applicable patients with mCRPC treated with docetaxel followed by abiraterone at our center. We analyzed progression-free survival (PFS) of docetaxel and abiraterone treatments. We further searched for predictive factors for the duration of treatment response. RESULTS: Median PFS between initiation of androgen deprivation therapy and the diagnosis of mCRPC was 32 months. Median PFS on docetaxel treatment was 9 months. Median PFS on abiraterone treatment was 11 months. Patients with higher Gleason scores (GS) (8-10) at initial diagnosis had a significantly longer median PFS on docetaxel as compared to patients with GS 6 7, p = 0.01. We demonstrate a significant correlation between the PFS on docetaxel and PFS on abiraterone in the post-docetaxel setting (Kendall tau r = 0.32, p = 0.019) as well as a significant negative correlation between the PSA nadir under abiraterone treatment and the time to progression under abiraterone (Kendall tau r = -0.43, p = 0.007). CONCLUSIONS: High Gleason score appears to be predictive of duration of response to docetaxel. Interestingly, progression-free survival with abiraterone appears to be correlated with the duration of response with docetaxel, whereas PSA decline and low nadir appear to be predictive of response to abiraterone. PMID- 25113806 TI - About the inevitable compromise between spatial resolution and accuracy of strain measurement for bone tissue: a 3D zero-strain study. AB - The accurate measurement of local strain is necessary to study bone mechanics and to validate micro computed tomography (uCT) based finite element (FE) models at the tissue scale. Digital volume correlation (DVC) has been used to provide a volumetric estimation of local strain in trabecular bone sample with a reasonable accuracy. However, nothing has been reported so far for uCT based analysis of cortical bone. The goal of this study was to evaluate accuracy and precision of a deformable registration method for prediction of local zero-strains in bovine cortical and trabecular bone samples. The accuracy and precision were analyzed by comparing scans virtually displaced, repeated scans without any repositioning of the sample in the scanner and repeated scans with repositioning of the samples. The analysis showed that both precision and accuracy errors decrease with increasing the size of the region analyzed, by following power laws. The main source of error was found to be the intrinsic noise of the images compared to the others investigated. The results, once extrapolated for larger regions of interest that are typically used in the literature, were in most cases better than the ones previously reported. For a nodal spacing equal to 50 voxels (498 um), the accuracy and precision ranges were 425-692 uepsilon and 202-394 uepsilon, respectively. In conclusion, it was shown that the proposed method can be used to study the local deformation of cortical and trabecular bone loaded beyond yield, if a sufficiently high nodal spacing is used. PMID- 25113801 TI - Impact of tissue-specific stem cells on lineage-specific differentiation: a focus on the musculoskeletal system. AB - Tissue-specific stem cells are found throughout the body and, with proper intervention and environmental cues, these stem cells exercise their capabilities for differentiation into several lineages to form cartilage, bone, muscle, and adipose tissue in vitro and in vivo. Interestingly, it has been widely demonstrated that they do not differentiate with the same efficacy during lineage specific differentiation studies, as the tissue-specific stem cells are generally more effective when differentiating toward the tissues from which they were derived. This review focuses on four mesodermal lineages for tissue-specific stem cell differentiation: adipogenesis, chondrogenesis, myogenesis, and osteogenesis. It is intended to give insight into current multilineage differentiation and comparative research, highlight and contrast known trends regarding differentiation, and introduce supporting evidence which demonstrates particular tissue-specific stem cells' superiority in lineage-specific differentiation, along with their resident tissue origins and natural roles. In addition, some epigenetic and transcriptomic differences between stem cells which may explain the observed trends are discussed. PMID- 25113807 TI - The role of transmembrane proteins on force transmission in skeletal muscle. AB - Lateral transmission of force from myofibers laterally to the surrounding extracellular matrix (ECM) via the transmembrane proteins between them is impaired in old muscles. Changes in geometrical and mechanical properties of ECM of skeletal muscle do not fully explain the impaired lateral transmission with aging. The objective of this study was to determine the role of transmembrane proteins on force transmission in skeletal muscle. In this study, a 2D finite element model of single muscle fiber composed of myofiber, ECM, and the transmembrane proteins between them was developed to determine how changes in spatial density and mechanical properties of transmembrane proteins affect the force transmission in skeletal muscle. We found that force transmission and stress distribution are not affected by mechanical stiffness of the transmembrane proteins due to its non-linear stress-strain relationship. Results also showed that the muscle fiber with insufficient transmembrane proteins near the end of muscle fiber transmitted less force than that with more proteins does. Higher stress was observed in myofiber, ECM, and proteins in the muscle fiber with fewer proteins. PMID- 25113808 TI - 3D finite element model of the diabetic neuropathic foot: a gait analysis driven approach. AB - Diabetic foot is an invalidating complication of diabetes that can lead to foot ulcers. Three-dimensional (3D) finite element analysis (FEA) allows characterizing the loads developed in the different anatomical structures of the foot in dynamic conditions. The aim of this study was to develop a subject specific 3D foot FE model (FEM) of a diabetic neuropathic (DNS) and a healthy (HS) subject, whose subject specificity can be found in term of foot geometry and boundary conditions. Kinematics, kinetics and plantar pressure (PP) data were extracted from the gait analysis trials of the two subjects with this purpose. The FEM were developed segmenting bones, cartilage and skin from MRI and drawing a horizontal plate as ground support. Materials properties were adopted from previous literature. FE simulations were run with the kinematics and kinetics data of four different phases of the stance phase of gait (heel strike, loading response, midstance and push off). FEMs were then driven by group gait data of 10 neuropathic and 10 healthy subjects. Model validation focused on agreement between FEM-simulated and experimental PP. The peak values and the total distribution of the pressures were compared for this purpose. Results showed that the models were less robust when driven from group data and underestimated the PP in each foot subarea. In particular in the case of the neuropathic subject's model the mean errors between experimental and simulated data were around the 20% of the peak values. This knowledge is crucial in understanding the aetiology of diabetic foot. PMID- 25113809 TI - Regarding: Udeh BL, et al. The 2-year Cost-effectiveness of 3 Options to Treat Lumbar Spinal Stenosis Patients. Pain Pract 2014 Jan 3 [epub ahead of print]. PMID- 25113810 TI - Relationship of CD146 expression to secretion of interleukin (IL)-17, IL-22 and interferon-gamma by CD4(+) T cells in patients with inflammatory arthritis. AB - Expression of the adhesion molecule, CD146/MCAM/MelCAM, on T cells has been associated with recent activation, memory subsets and T helper type 17 (Th17) effector function, and is elevated in inflammatory arthritis. Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA) and spondyloarthritides (SpA). Here, we compared the expression of CD146 on CD4(+) T cells between healthy donors (HD) and patients with RA and SpA [ankylosing spondylitis (AS) or psoriatic arthritis (PsA)] and examined correlations with surface markers and cytokine secretion. Peripheral blood mononuclear cells (PBMC) were obtained from patients and controls, and synovial fluid mononuclear cells (SFMC) from patients. Cytokine production [elicited by phorbol myristate acetate (PMA)/ionomycin] and surface phenotypes were evaluated by flow cytometry. CD146(+) CD4(+) and interleukin (IL)-17(+) CD4(+) T cell frequencies were increased in PBMC of PsA patients, compared with HD, and in SFMC compared with PBMC. CD146(+) CD4(+) T cells were enriched for secretion of IL-17 [alone or with IL-22 or interferon (IFN)-gamma] and for some putative Th17-associated surface markers (CD161 and CCR6), but not others (CD26 and IL-23 receptor). CD4(+) T cells producing IL-22 or IFN-gamma without IL-17 were also present in the CD146(+) subset, although their enrichment was less marked. Moreover, a majority of cells secreting these cytokines lacked CD146. Thus, CD146 is not a sensitive or specific marker of Th17 cells, but rather correlates with heterogeneous cytokine secretion by subsets of CD4(+) helper T cells. PMID- 25113812 TI - Using a thermoluminescent dosimeter to evaluate the location reliability of the highest-skin dose area detected by treatment planning in radiotherapy for breast cancer. AB - Acute skin reaction during adjuvant radiotherapy for breast cancer is an inevitable process, and its severity is related to the skin dose. A high-skin dose area can be speculated based on the isodose distribution shown on a treatment planning. To determine whether treatment planning can reflect high-skin dose location, 80 patients were collected and their skin doses in different areas were measured using a thermoluminescent dosimeter to locate the highest-skin dose area in each patient. We determined whether the skin dose is consistent with the highest-dose area estimated by the treatment planning of the same patient. The chi(2) and Fisher exact tests revealed that these 2 methods yielded more consistent results when the highest-dose spots were located in the axillary and breast areas but not in the inframammary area. We suggest that skin doses shown on the treatment planning might be a reliable and simple alternative method for estimating the highest skin doses in some areas. PMID- 25113813 TI - Dosimetric comparison of intensity-modulated solutions for intact prostate cancer. AB - The purpose of this study is intended to investigate the implementation of a modified class solution for intact prostate intensity-modulated radiation therapy (IMRT). The class solution uses 2 additional optimization structures intended to increase target conformity and decrease unnecessary dose to healthy tissue. A total of 10 randomly selected intact prostate IMRT patients were chosen for this retrospective study. Each of the original IMRT plans was compared with a modified class solution. The class solution implemented 2 additional optimization structures. The 95_OPT was intended to increase target conformity, and the Avoidance_3780 was intended to reduce normal tissue. Each plan was evaluated for minimum, maximum, and mean doses to the target. Additionally, mean normal tissue dose, total monitor units (MUs), and segments were investigated. Conformity index and normal healthy index were also compared. All comparisons were evaluated using a paired t-test using GraphPad software. Evaluations of MUs; segments; minimum, maximum, mean target doses; mean normal tissue dose; and conformity index did not demonstrate a significant difference between the modified class solution and the original plans. However, evaluation of healthy tissue conformity index indicated a significant difference. Overall, 70% of the original plans failed to demonstrate a satisfactory score (< 0.6) of properly sparing normal healthy tissue, whereas 70% of the modified plans exhibited a satisfactory score (> 0.6). Most (90%) of the modified plans demonstrated a greater number of segments than the compared original plan. A modified class solution provides a good starting point for planning intact prostate cancer. The addition of the Avoidance_3780 structure increases the healthy tissue conformity index score. PMID- 25113814 TI - Effect of local heating on postprandial blood glucose excursions using the InsuPad device: results of an outpatient crossover study. AB - The InsuPad is a medical device to accelerate insulin resorption by applying local heat at the insulin injection site. This crossover study examined the impact of the InsuPad use on postprandial glucose excursions under daily life conditions. In 1 study phase, diabetic patients used the InsuPad when injecting bolus insulin before breakfast and dinner and measured their blood glucose 5 times daily (before breakfast, lunch, and dinner and after breakfast and dinner). In the other study phase, blood glucose measurements were maintained without using the InsuPad. The order of the study phases was randomized. Twenty patients with a high insulin demand took part (30% type 1 diabetes, age 53.7 +/- 8.9 years, diabetes duration 14.9 +/- 7.4 years; HbA1c 8.3 +/- 0.8%; total daily insulin demand 0.97 +/- 0.32 IU per kg). Postprandial glucose excursion was reduced by 15.4 mg/dl (95% CI 9.7-21.2 mg/dl; P = .011) after breakfast and dinner if InsuPad was used. The mean blood glucose was lower by 8.8 mg/dl (95% CI 0:3-18:0 mg/dl; P = .099) when using the InsuPad. Safety parameters and the percentage of hypoglycemic (< 60 mg/dl) or hyperglycemic (> 300 mg/dl) blood glucose measurements were not negatively affected by InsuPad use (hypoglycemic values 1.4% vs 1.5%, P = .961; hyperglycemic values 2.6% vs 4.0%, P = .098). Local heating of the insulin injection site by use of the InsuPad device is an effective and safe method to reduce postprandial blood glucose excursions under daily life conditions without negative side effects on the occurrence of low or high blood glucose values. PMID- 25113815 TI - Nitric oxide reactivity of [2Fe-2S] clusters leading to H2S generation. AB - The crosstalk between two biologically important signaling molecules, nitric oxide (NO) and hydrogen sulfide (H2S), proceeds via elusive mechanism(s). Herein we report the formation of H2S by the action of NO on synthetic [2Fe-2S] clusters when the reaction environment is capable of providing a formal H(*) (e(-)/H(+)). Nitrosylation of (NEt4)2[Fe2S2(SPh)4] (1) in the presence of PhSH or (t)Bu3PhOH results in the formation of (NEt4)[Fe(NO)2(SPh)2] (2) and H2S with the concomitant generation of PhSSPh or (t)Bu3PhO(*). The amount of H2S generated is dependent on the electronic environment of the [2Fe-2S] cluster as well as the type of H(*) donor. Employment of clusters with electron-donating groups or H(*) donors from thiols leads to a larger amount of H2S evolution. The 1/NO reaction in the presence of PhSH exhibits biphasic decay kinetics with no deuterium kinetic isotope effect upon PhSD substitution. However, the rates of decay increase significantly with the use of 4-MeO-PhSH or 4-Me-PhSH in place of PhSH. These results provide the first chemical evidence to suggest that [Fe-S] clusters are likely to be a site for the crosstalk between NO and H2S in biology. PMID- 25113816 TI - Determinants of glycaemic control in a practice setting: the role of weight loss and treatment adherence (The DELTA Study). AB - AIMS: Examine the association between weight loss and adherence with glycaemic goal attainment in patients with inadequately controlled T2DM. MATERIALS AND METHODS: Patients >= 18 years with T2DM from a US integrated health system starting a new class of diabetes medication between 11/1/10 and 4/30/11 (index date) with baseline HbA1c >= 7.0% were included in this cohort study. Target HbA1c and weight change were defined at 6-months as HbA1c < 7.0% and >= 3% loss in body weight. Patient-reported medication adherence was assessed per the Medication Adherence Reporting Scale. Structural equation modelling was used to describe simultaneous associations between adherence, weight loss and HbA1c goal attainment. RESULTS: Inclusion criteria were met by 477 patients; mean (SD) age 59.1 (11.6) years; 50.9% were female; 30.4% were treatment naive; baseline HbA1c 8.6% (1.6); weight 102.0 kg (23.0). Most patients (67.9%) reported being adherent to the index diabetes medication. At 6 months mean weight change was -1.3 (5.1) kg (p = 0.39); 28.1% had weight loss of >= 3%. Mean HbA1c change was -1.2% (1.8) (p< 0.001); 42.8% attained HbA1c goal. Adherent patients (OR 1.70; p = 0.02) and diabetes therapies that lead to weight loss (metformin, GLP-1) were associated with weight loss >= 3% (OR 2.96; p< 0.001). Weight loss (OR 3.60; p < 0.001) and adherence (OR 1.59; p < 0.001) were associated with HbA1c goal attainment. CONCLUSIONS: Weight loss >= 3% and medication adherence were associated with HbA1c goal attainment in T2DM; weight loss was a stronger predictor of goal attainment than medication adherence in this study population. It is important to consider weight-effect properties, in addition to patient-centric adherence counselling, when prescribing diabetes therapy. PMID- 25113817 TI - A feature selection method for classification within functional genomics experiments based on the proportional overlapping score. AB - BACKGROUND: Microarray technology, as well as other functional genomics experiments, allow simultaneous measurements of thousands of genes within each sample. Both the prediction accuracy and interpretability of a classifier could be enhanced by performing the classification based only on selected discriminative genes. We propose a statistical method for selecting genes based on overlapping analysis of expression data across classes. This method results in a novel measure, called proportional overlapping score (POS), of a feature's relevance to a classification task. RESULTS: We apply POS, along-with four widely used gene selection methods, to several benchmark gene expression datasets. The experimental results of classification error rates computed using the Random Forest, k Nearest Neighbor and Support Vector Machine classifiers show that POS achieves a better performance. CONCLUSIONS: A novel gene selection method, POS, is proposed. POS analyzes the expressions overlap across classes taking into account the proportions of overlapping samples. It robustly defines a mask for each gene that allows it to minimize the effect of expression outliers. The constructed masks along-with a novel gene score are exploited to produce the selected subset of genes. PMID- 25113818 TI - Effects of skin-to-skin contact and breastfeeding at birth on the incidence of PPH: A physiologically based theory. AB - BACKGROUND: The importance of optimising maternal/baby psychophysiology has been integrated into contemporary midwifery theories but not in the detail required to really understand the underpinning biological basis. METHOD: The functioning of the autonomic nervous system, as it relates to the uterus is reviewed. The physiology of myometrial cell contraction and relaxation is outlined. The main focus is on the factors that affect the availability and uptake of oxytocin and adrenaline/noradrenaline in the myometrial cells. These are the two key neuro hormones, active in the 3rd and 4th stages of labour, that affect uterine contraction and retraction and therefore determine whether the woman will have an atonic PPH or not. DISCUSSION: The discussion explains and predicts the physiological functioning of the uterus during the 3rd and 4th stages of labour when skin-to-skin contact and breastfeeding occurs and when it does not. CONCLUSION: This biologically based theory hypothesises that to achieve and maintain eutony and eulochia, midwives and birthing women should ensure early, prolonged and undisturbed skin-to-skin contact for mother and baby at birth including easy access for spontaneous breastfeeding. PMID- 25113819 TI - Targeting perfectionism in anorexia nervosa using a group-based cognitive behavioural approach: a pilot study. AB - OBJECTIVE: This study aimed to explore whether a six session cognitive behavioural group intervention targeting perfectionism is efficacious in reducing perfectionism in adults with anorexia nervosa in an inpatient setting. METHOD: Adults with anorexia nervosa received a group perfectionism intervention in an inpatient setting. Self-report and patient satisfaction questionnaires were completed at the beginning of the first session and end of the last session. RESULTS: Significant changes of moderate effect size were observed for overall perfectionism, concern over mistakes and personal standards dimensions of perfectionism following participation in the group. These changes were found to be independent of change in body mass index. CONCLUSIONS: A group cognitive behavioural approach appears to be efficacious in reducing perfectionism in adults with anorexia nervosa. PMID- 25113820 TI - Characteristics impacting on session rating of perceived exertion training load in Australian footballers. AB - The relationship between external training load and session rating of perceived exertion (s-RPE) training load and the impact that playing experience, playing position and 2-km time-trial performance had on s-RPE training load were explored. From 39 Australian Football players, 6.9 +/- 4.6 training sessions were analysed, resulting in 270 samples. Microtechnology devices provided external training load (distance, average speed, high-speed running distance, player load (PL) and player loadslow (PLslow)). The external training load measures had moderate to very large associations (r, 95% CI) with s-RPE training load, average speed (0.45, 0.35-0.54), high-speed running distance (0.51, 0.42-0.59), PLslow (0.80, 0.75-0.84), PL (0.86, 0.83-0.89) and distance (0.88, 0.85-0.90). Differences were described using effect sizes (d +/-95% CL). When controlling for external training load, the 4- to 5-year players had higher s-RPE training load than the 0- to 1- (0.44 +/- 0.33) and 2- to 3-year players (0.51 +/- 0.30), ruckmen had moderately higher s-RPE training load than midfielders (0.82 +/- 0.58), and there was a 0.2% increase in s-RPE training load per 1 s increase in time-trial (95% CI: 0.07-0.34). Experience, position and time-trial performance impacted the relationship between external training load and s-RPE training load. This suggests that a given external training load may result in different internal responses between athletes, potentially leaving individuals at risk of overtraining or failing to elicit positive adaptation. It is therefore vital that coaches and trainers give consideration to these mediators of s-RPE training load. PMID- 25113824 TI - Revision of the fish family Kyphosidae (Teleostei: Perciformes). AB - A molecular phylogenetic analysis with complete species sampling of the family Kyphosidae revealed several discrepancies with the current taxonomy. We thus undertook a complete taxonomic revision of all kyphosid genera, i.e. Kyphosus Lacepede, 1801, and the monotypic Hermosilla Jenkins and Evermann, 1889, Sectator Jordan and Evermann, 1903 and Neoscorpis Smith, 1931. Species delimitation was determined on the basis of congruence between (a) monophyletic groupings in the molecular phylogeny, and (b) clusters of morphological variation in type material. Twelve species are supported and redescribed. Both Hermosilla and Sectator are considered junior synonyms of Kyphosus. Kyphosus azureus (Jenkins & Evermann, 1889) and K. ocyurus (Jordan & Gilbert, 1882) are redescribed accordingly. We designate a neotype for Kyphosus cornelii (Whitley, 1944), as the original material is lost, and new material was collected at the type locality for this study to facilitate comparison with other species of Kyphosus. Kyphosus sandwicensis (sensu Sauvage, 1880) was found to be a junior synonym of K. elegans (Peters, 1869). Kyphosus incisor (Cuvier in Cuvier & Valenciennes, 1831) and K. analogus (Gill, 1862) are considered junior synonyms of K. vaigiensis (Quoy & Gaimard, 1825). Kyphosus gallveii (Cunningham, 1910), K. pacificus Sakai and Nakabo, 2004 and K. lutescens (Jordan & Gilbert, 1882) are all considered junior synonyms of K. sectatrix (Linnaeus, 1758). One of the two syntype specimens of K. sectatrix was identified as the holotype of Pimelepterus bosquii (Lacepede, 1802), and proved to be a specimen of K. bigibbus Lacepede, 1801. This specimen is re-assigned as a non-type of K. bigibbus. Full re-descriptions of the following valid species are presented: K. bigibbus, K. cinerascens (Forsskal, 1775), K. cornelii, K. elegans, K. hawaiiensis Sakai and Nakabo, 2004, K. gladius Knudsen and Clements, 2013, K. sydneyanus (Gunther, 1886) and K. vaigiensis, together with a key to the family. The distribution of Kyphosus species is reconsidered based on our taxonomic revision, indicating that four species (K. bigibbus, K. cinerascens, K. sectatrix and K. vaigiensis) occur in both the Atlantic and Indo-Pacific regions. PMID- 25113821 TI - Impact of single-cell genomics and metagenomics on the emerging view of extremophile "microbial dark matter". AB - Despite >130 years of microbial cultivation studies, many microorganisms remain resistant to traditional cultivation approaches, including numerous candidate phyla of bacteria and archaea. Unraveling the mysteries of these candidate phyla is a grand challenge in microbiology and is especially important in habitats where they are abundant, including some extreme environments and low-energy ecosystems. Over the past decade, parallel advances in DNA amplification, DNA sequencing and computing have enabled rapid progress on this problem, particularly through metagenomics and single-cell genomics. Although each approach suffers limitations, metagenomics and single-cell genomics are particularly powerful when combined synergistically. Studies focused on extreme environments have revealed the first substantial genomic information for several candidate phyla, encompassing putative acidophiles (Parvarchaeota), halophiles (Nanohaloarchaeota), thermophiles (Acetothermia, Aigarchaeota, Atribacteria, Calescamantes, Korarchaeota, and Fervidibacteria), and piezophiles (Gracilibacteria). These data have enabled insights into the biology of these organisms, including catabolic and anabolic potential, molecular adaptations to life in extreme environments, unique genomic features such as stop codon reassignments, and predictions about cell ultrastructure. In addition, the rapid expansion of genomic coverage enabled by these studies continues to yield insights into the early diversification of microbial lineages and the relationships within and between the phyla of Bacteria and Archaea. In the next 5 years, the genomic foliage within the tree of life will continue to grow and the study of yet-uncultivated candidate phyla will firmly transition into the post genomic era. PMID- 25113823 TI - Natural anionic polymer acts as highly efficient trypsin inhibitor based on an electrostatic interaction mechanism. AB - Sodium alginate (SA), acting as a trypsin inhibitor by means of electrostatic interaction, is studied. The half-maximal inhibitory concentration (IC50 = 0.05 MUg mL(-1) ) of this natural anionic polymer is about 400 times lower than that of commercial soybean trypsin inhibitor (STI). Unlike the Ca(2+) -deprivation mechanisms, its inhibition may be attributed to preventing the trypsin active site (TAS) from accessing the macromolecular substrates instead of denaturing it. SA is an efficient, innocuous, and cost-effective inhibitory excipient that can be conveniently used in many peptide and protein dosage formulations. PMID- 25113822 TI - Dark matter in archaeal genomes: a rich source of novel mobile elements, defense systems and secretory complexes. AB - Microbial genomes encompass a sizable fraction of poorly characterized, narrowly spread fast-evolving genes. Using sensitive methods for sequences comparison and protein structure prediction, we performed a detailed comparative analysis of clusters of such genes, which we denote "dark matter islands", in archaeal genomes. The dark matter islands comprise up to 20% of archaeal genomes and show remarkable heterogeneity and diversity. Nevertheless, three classes of entities are common in these genomic loci: (a) integrated viral genomes and other mobile elements; (b) defense systems, and (c) secretory and other membrane-associated systems. The dark matter islands in the genome of thermophiles and mesophiles show similar general trends of gene content, but thermophiles are substantially enriched in predicted membrane proteins whereas mesophiles have a greater proportion of recognizable mobile elements. Based on this analysis, we predict the existence of several novel groups of viruses and mobile elements, previously unnoticed variants of CRISPR-Cas immune systems, and new secretory systems that might be involved in stress response, intermicrobial conflicts and biogenesis of novel, uncharacterized membrane structures. PMID- 25113825 TI - Topological defects in cholesteric liquid crystals induced by monolayer domains with orientational chirality. AB - Unless stabilized by colloids or confinement with well-defined boundary conditions, defects in liquid crystals remain elusive short-lived objects that tend to disappear with time to minimize the medium's free energy. In this work we use multimodal three-dimensional imaging to visualize cholesteric director structures to show that self-assembled chiral molecular monolayer domains can stabilize topologically constrained defect configurations when in contact with a cholesteric liquid crystal. The cholesteric liquid crystal, having features of both coarse-grained lamellar and nematic liquid crystal with chiral symmetry breaking, allows us to explore the interplay of chirality and implications of layering on the formed defects and director configurations. PMID- 25113826 TI - Desulfurization of thianthrene by a Gordonia sp. IITR100. AB - Thianthrene (TA) was desulfurized by an isolated strain, Gordonia sp. IITR100. The reaction is accompanied with the formation of TA-sulfoxide, TA-sulfone and 2 phenylsulfanylphenol. The formed 2-phenylsulfanylphenol undergoes further oxidation to o-hydroxyphenyl phenylsulfone that accumulates as an end product. Metabolism of TA to TA-sulfone can also occur by E. coli-DszC i.e. E. coli cells that were harboring the gene coding for the enzyme dibenzothiophene desulfurase C. When presented to E. coli-DszC in a binary combination with dibenzothiophene, TA metabolism was completely inhibited. Metabolism of TA-TA-sulfone by E. coli DszC, as well as the nature of metabolites formed by IITR100, suggests that the desulfurization pathway for TA is similar to that of the thiophenic compounds. This is first report on the desulfurization of thianthrene, and has implications on biodesulfurization when multiple sulfur compounds are present together. PMID- 25113827 TI - [Organ and function preservation in urethral cancer]. AB - Primary urethral carcinomas are rare tumors that can occur both in men and women. Histological patterns of these tumors are mixed, urothelial tumors occur as well as squamous cell tumors or adenocarcinomas.There are different clinical factors that define clinical prognosis, and the 1- and 5-year cancer-free survival is 75% and 54%. Therapy of locally limited disease is surgical resection, and organ preserving treatment is possible if negative frozen sections prove complete surgical resection. However, in men a perineal urethrostomy might be necessary, and in women there is a high risk of urinary incontinence if more than 2 cm of the distal urethra is resected.In case of locally advanced tumors or tumors of the proximal urethra, a radical urethrectomy with supravesical urinrary diversion is necessary. In some cases neoadjuvant (radio-)chemotherapy may be an option. PMID- 25113828 TI - Facile, one-pot solvothermal method to synthesize ultrathin Sb2S3 nanosheets anchored on graphene. AB - Ultrathin, two-dimensional (2D) nanosheets of layered transition-metal chalcogenides are theoretically and technologically intriguing. However, it still remains a great challenge to synthesize ultrathin nanosheets because of the lack of an intrinsic driving force for the anisotropic growth of 2D superposed microstructures. Here we demonstrate, for the first time to our knowledge, the in situ synthesis of large-scale ultrathin Sb2S3 nanosheets on graphene sheets (G) by solvothermal method in a water-ethylene glycol mixed solvent. Owing to the synergetic chemical coupling effects between G and Sb2S3, Sb2S3-G hybrid nanosheets exhibit high catalytic performance for the degradation of methylene blue in the presence of H2O2. Moreover, it was found that the resulting Sb2S3-G shows good electrocatalytic activity towards hydrazine oxidation. This work not only offers a low-cost and high performance alternative technology for synthesizing sheet-like Sb2S3, but also opens the door toward the fabrication of varying types of metal sulfide-graphene nanomaterials that will have wide applications in catalysis, environmental, and new energy fields. PMID- 25113830 TI - External NAD(P)H dehydrogenases in Acanthamoeba castellanii mitochondria. AB - The mitochondrial respiratory chain of plants and some fungi contains multiple rotenone-insensitive NAD(P)H dehydrogenases, of which at least two are located on the outer surface of the inner membrane (i.e., external NADH and external NADPH dehydrogenases). Annotated sequences of the putative alternative NAD(P)H dehydrogenases of the protozoan Acanthamoeba castellanii demonstrated similarity to plant and fungal sequences. We also studied activity of these dehydrogenases in isolated A. castellanii mitochondria. External NADPH oxidation was observed for the first time in protist mitochondria. The coupling parameters were similar for external NADH oxidation and external NADPH oxidation, indicating similar efficiencies of ATP synthesis. Both external NADH oxidation and external NADPH oxidation had an optimal pH of 6.8 independent of relevant ubiquinol-oxidizing pathways, the cytochrome pathway or a GMP-stimulated alternative oxidase. The maximal oxidizing activity with external NADH was almost double that with external NADPH. However, a lower Michaelis constant (K(M)) value for external NADPH oxidation was observed compared to that for external NADH oxidation. Stimulation by Ca(2+) was approximately 10 times higher for external NADPH oxidation, while NADH dehydrogenase(s) appeared to be slightly dependent on Ca(2+). Our results indicate that external NAD(P)H dehydrogenases similar to those in plant and fungal mitochondria function in mitochondria of A. castellanii. PMID- 25113829 TI - The social amoeba Polysphondylium pallidum loses encystation and sporulation, but can still erect fruiting bodies in the absence of cellulose. AB - Amoebas and other freely moving protists differentiate into walled cysts when exposed to stress. As cysts, amoeba pathogens are resistant to biocides, preventing treatment and eradication. Lack of gene modification procedures has left the mechanisms of encystation largely unexplored. Genetically tractable Dictyostelium discoideum amoebas require cellulose synthase for formation of multicellular fructifications with cellulose-rich stalk and spore cells. Amoebas of its distant relative Polysphondylium pallidum (Ppal), can additionally encyst individually in response to stress. Ppal has two cellulose synthase genes, DcsA and DcsB, which we deleted individually and in combination. Dcsa- mutants formed fruiting bodies with normal stalks, but their spore and cyst walls lacked cellulose, which obliterated stress-resistance of spores and rendered cysts entirely non-viable. A dcsa-/dcsb- mutant made no walled spores, stalk cells or cysts, although simple fruiting structures were formed with a droplet of amoeboid cells resting on an sheathed column of decaying cells. DcsB is expressed in prestalk and stalk cells, while DcsA is additionally expressed in spores and cysts. We conclude that cellulose is essential for encystation and that cellulose synthase may be a suitable target for drugs to prevent encystation and render amoeba pathogens susceptible to conventional antibiotics. PMID- 25113831 TI - Molecular revision of the genus Wallaceina. AB - This work is focused on the molecular revision of the genus Wallaceina established in the very twilight of the classical morphotype-based approach to classification of the Trypanosomatidae. The genus was erected due to the presence of a unique variant of endomastigotes. In molecular phylogenetic studies four described species of Wallaceina were shown to be extremely close to each other and to some other undescribed isolates clustered within Leishmaniinae clade, while three recently included species formed a separate clade. Our results of morphological and molecular phylogenetic analyses demonstrated that all Leishmaniinae-bound wallaceinas are just different isolates of the same species that we rename back to Crithidia brevicula Frolov, Malysheva, 1989. To accommodate former Wallaceina spp. phylogenetically distant from the genus Crithidia, we propose a new generic name Wallacemonas Kostygov et Yurchenko, 2014. PMID- 25113832 TI - Associations between body mass and papillary thyroid cancer stage and tumor size: a population-based study. AB - PURPOSE: The incidence of large thyroid tumors has increased over the past decades, suggesting that improved diagnosis is not the only driver of increased thyroid cancer incidence. Obesity has recently been implicated as an independent risk factor for thyroid cancer in specific populations. We aimed to investigate whether thyroid tumor size and advanced stage of diagnosis is associated with the obesity epidemic, for the first time, in a US population-based cohort. METHODS: We leveraged existing data and linked 1,077 papillary thyroid cancer patients from the Nevada Central Cancer Registry to the Department of Motor Vehicle dataset. Tumor size and cancer stage were assessed from cancer registry records, and obesity was obtained using height and weight in the Department of Motor Vehicle records and measured by a body mass index greater than 25 kg/m(2). RESULTS: Crude analysis showed obesity as was associated with tumors larger than 2 cm [odds ratio (OR) 1.50, p = 0.0423] and advanced cancer stage (stage III and IV) (OR 1.40, p = 0.0111). After adjusting for confounders, a significant association was still observed between obesity and tumor larger than 2 cm (OR 1.53, p = 0.0339). A marginally significant association was shown between obesity and advanced cancer stage (OR 1.29, p = 0.0649). CONCLUSION: As thyroid cancer incidence continues to increase, this study's finding that obesity was significantly associated with larger tumor size and marginally significantly associated with advanced tumor stage can help establish new preventative actions and identify new target populations for interventions. PMID- 25113833 TI - Effect of different sulfides on cadmium distribution during sludge combustion based on experimental and thermodynamic calculation approaches. AB - The effects of sulfur compounds on the migration of a semi-volatile heavy metal (cadmium) during sludge incineration were investigated with two methods, i.e., experiments in a tubular furnace reactor and thermodynamic equilibrium calculations. The representative typical sludge with and without the addition of sulfur compounds was incinerated at 850 degrees C. The partitioning of Cd among the solid phase (bottom ash) and gas phase (fly ash and flue gas) was quantified. The results indicate that sulfur compounds in the elemental form and a reduced state could stabilize Cd in the form of CdS, aluminosilicate minerals, and polymetallic sulfides, whereas sulfur in the oxidized forms slightly increases Cd volatilization during incineration. For Cd solidification points, the inhibition effect on the volatilization of Cd is as follows: S > Na2SO4 > Na2S. Chemical equilibrium calculations indicate that sulfur binds with Cd and alters Cd speciation at low temperatures (<950 K). Furthermore, SiO2- and Al2O3-containing minerals can function as sorbents stabilizing Cd as condensed phase solids (CdSiO4 and CdAl2O4) according to the results of equilibrium calculations. These findings provide useful information for understanding the partitioning of Cd and thus facilitate the development of strategies to control Cd volatilization during sludge incineration. PMID- 25113834 TI - In vivo toxicity of orally administrated silicon dioxide nanoparticles in healthy adult mice. AB - The increasing use of silica nanoparticles (SiNPs) in various applications including industrial, agriculture, and medicine has raised concerns about their potential risks to human health. Various nanotoxicity researches have been done on the assessment of SiNPs' toxic effects; however, a few in vivo investigations exist. In this investigation, an in vivo study was done in order to evaluate the oral toxicity of SiNPs. The biochemical levels of 19 different serum parameters were assessed. Moreover, the histopathological changes have been examined as well. We showed that SiNPs with diameters of 10-15 nm in size can cause significant changes in albumin, cholesterol, triglyceride, total protein, urea, HDL, and LDL as well as in alkaline phosphatase and aspartate aminotransferase activity. In addition, histopathological examinations demonstrated that SiNPs have toxic effects on various tissues including liver, kidney, lung, and testis. PMID- 25113835 TI - PEGylated carboxyhemoglobin bovine (SANGUINATE): results of a phase I clinical trial. AB - PEGylated carboxyhemoglobin bovine (SANGUINATE) is a dual action carbon monoxide releasing (CO)/oxygen (O2 ) transfer agent for the treatment of hypoxia. Its components inhibit vasoconstriction, decrease extravasation, limit reactive oxygen species production, enhance blood rheology, and deliver oxygen to the tissues. Animal models of cerebral ischemia, peripheral ischemia, and myocardial ischemia demonstrated SANGUINATE's efficacy in reducing myocardial infarct size, limiting necrosis from cerebral ischemia, and promoting more rapid recovery from hind limb ischemia. In a Phase I trial, three cohorts of eight healthy volunteers received single ascending doses of 80, 120, or 160 mg/kg of SANGUINATE. Two volunteers within each cohort served as a saline control. There were no serious adverse events. Serum haptoglobin decreased, but did not appear to be dose related. The T1/2 was dose dependent and ranged from 7.9 to 13.8 h. In addition to the Phase I trial, SANGUINATE was used under an expanded access emergency Investigational New Drug. SANGUINATE was found to be safe and well tolerated in a Phase I clinical trial, and therefore it will advance into further clinical trials in patients. PMID- 25113836 TI - Mitochondrial dynamics controlled by mitofusins define organelle positioning and movement during mouse oocyte maturation. AB - Mitochondria are abundant in fully grown mammalian oocytes with a unique spherical morphology, but the mechanisms controlling mitochondria behavior are not well understood. Here we describe for the first time the control of mitochondrial behavior in mouse oocytes by a fusion/fission mechanism. Mitofusins (Mfn1 and Mfn2) and OPA1 proteins are required for outer and inner mitochondrial membrane fusion, respectively, whereas Drp1 is the key regulator of mitochondrial fission. We show that mouse oocytes express the Mfn1, Mfn2, Opa1 and Drp1 proteins, both in immature and mature oocytes at similar levels. Overexpression of Mfn1 or Mfn2 causes marked mitochondrial aggregation, particularly in the perinuclear region during meiotic progression. Tracking of mitochondria with chromosomes or endoplasmic reticulum (ER) throughout oocyte maturation demonstrates that Mfn1 and Mfn2-promoted mitochondrial aggregation disturbs the spatiotemporal dynamic of the chromosomes and ER, respectively. Our findings suggest that organelle dynamics are co-ordinately controlled during meiotic division, and an imbalance of mitochondrial fusion/fission leads to disorganization of the organelle compartments. PMID- 25113837 TI - Fluid overload in a South African pediatric intensive care unit. AB - OBJECTIVE: Fluid resuscitation is integral to resuscitation guidelines and critical care. However, fluid overload (FO) yields increased morbidity. METHODS: Prospective observational study of Red Cross War Memorial Children's Hospital pediatric intensive care unit admissions (February to March 2013). FO % = (fluid in minus fluid out) [liters]/weight [kg] * 100%. PRIMARY OUTCOMES: FO >= 10%, 28 day mortality. RESULTS: Median [interquartile range (IQR)] age: 9.5 (2.0-39.0) months, median (IQR) admission weight: 7.9 (3.6-13.7) kg. Median (IQR) FO with admission weight: 3.5 (2.1-4.9)%; three patients had FO >= 10%. The 28 day mortality was 10% (n = 10). Patients who died had higher mean (IQR) FO using admission weight [4.9 (2.9-9.3)% vs. 3.4 (1.9-4.8)%; p = 0.04]. CONCLUSIONS: Low FO >= 10% prevalence with 28 day mortality 10%. Higher FO% with admission weight associated with mortality (p = 0.04). We advocate further investigation of FO% as a simple bedside tool. PMID- 25113838 TI - Drug therapy: keeping rats in the dark sheds light on tamoxifen resistance. PMID- 25113841 TI - Genetics: new molecular classification of gastric adenocarcinoma proposed by The Cancer Genome Atlas. PMID- 25113839 TI - Cancer-related fatigue--mechanisms, risk factors, and treatments. AB - Fatigue is one of the most common adverse effects of cancer that might persist for years after treatment completion in otherwise healthy survivors. Cancer related fatigue causes disruption in all aspects of quality of life and might be a risk factor of reduced survival. The prevalence and course of fatigue in patients with cancer have been well characterized and there is growing understanding of the underlying biological mechanisms. Inflammation seems to have a key role in fatigue before, during, and after cancer-treatment. However, there is a considerable variability in the presentation of cancer-related fatigue, much of which is not explained by disease-related or treatment-related characteristics, suggesting that host factors might be important in the development and persistence of this symptom. Indeed, longitudinal studies have identified genetic, biological, psychosocial, and behavioural risk factors associated with cancer-related fatigue. Although no current gold-standard treatment for fatigue is available, a variety of intervention approaches have shown beneficial effects in randomized controlled trials, including physical activity, psychosocial, mind-body, and pharmacological treatments. This Review describes the mechanisms, risk factors, and possible interventions for cancer related fatigue, focusing on recent longitudinal studies and randomized trials that have targeted fatigued patients. PMID- 25113843 TI - l-carnitine supplementation during vitrification of mouse germinal vesicle stage oocytes and their subsequent in vitro maturation improves meiotic spindle configuration and mitochondrial distribution in metaphase II oocytes. AB - STUDY QUESTION: How does l-carnitine (LC) supplementation during vitrification and in vitro maturation (IVM) of germinal vesicle stage (GV)-oocytes improve the developmental competence of the resultant metaphase II (MII) oocytes? SUMMARY ANSWER: LC supplementation during both vitrification of GV-oocytes and their subsequent IVM improved nuclear maturation as well as meiotic spindle assembly and mitochondrial distribution in MII oocytes. WHAT IS KNOWN ALREADY: Vitrification of GV-oocytes results in a lower success rate of blastocyst development compared with non-vitrified oocytes. LC supplementation during both vitrification and IVM of mouse GV-oocytes significantly improves embryonic development after IVF. STUDY DESIGN, SIZE, DURATION: GV-oocytes were collected from (B6.DBA)F1 and B6 mouse strains and subjected to vitrification and warming with or without 3.72 mM LC supplementation. After IVM with or without LC supplementation, the rate of nuclear maturation and the quality of MII oocytes were evaluated. At least 20 oocytes/group were examined, and each experiment was repeated at least three times. All experiments were conducted during 2013-2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Extrusion of the first polar body in IVM oocytes was observed as an indication of nuclear maturation. Spindle assembly and chromosomal alignment were examined by immunostaining of alpha-tubulin and nuclear staining with 4,6-diamidino-2-phenylindole (DAPI). Mitochondrial distribution and oxidative activity were measured by staining with Mitotracker Green Fluorescence Mitochondria (Mitotracker Green FM) and chloromethyltetramethylrosamine (Mitotracker Orange CMTMRos), respectively. ATP levels were determined by using the Bioluminescent Somatic Cell Assay Kit. MAIN RESULTS AND THE ROLE OF CHANCE: LC supplementation during both vitrification and IVM of GV-oocytes significantly increased the proportions of oocytes with normal MII spindles to the levels comparable with those of non-vitrified oocytes in both mouse strains. While vitrification of GV-oocytes lowered the proportions of MII oocytes with peripherally concentrated mitochondrial distribution compared with non-vitrified oocytes, LC supplementation significantly increased the proportion of such oocytes in the (B6.DBA)F1 strain. LC supplementation decreased the proportion of oocytes with mitochondrial aggregates in both vitrified and non vitrified oocytes in the B6 strain. The oxidative activity of mitochondria was mildly decreased by vitrification and drastically increased by LC supplementation irrespective of vitrification in both mouse strains. No change was found in ATP levels irrespective of vitrification or LC supplementation. Results were considered to be statistically significant at P < 0.05 by either chi(2)- or t test. LIMITATIONS, REASONS FOR CAUTION: It remains to be tested whether beneficial effect of LC supplementation during vitrification and IVM of GV oocytes leads to fetal development and birth of healthy offspring after embryo transfer to surrogate females. WIDER IMPLICATIONS OF THE FINDINGS: This protocol has the potential to improve the quality of vitrified human oocytes and embryos during assisted reproduction treatment. STUDY FUNDING/COMPETING INTEREST: Partially supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant and Mitacs Elevate Postdoctoral Fellowship, Canada. PMID- 25113842 TI - Quantitative multimodality imaging in cancer research and therapy. AB - Advances in hardware and software have enabled the realization of clinically feasible, quantitative multimodality imaging of tissue pathophysiology. Earlier efforts relating to multimodality imaging of cancer have focused on the integration of anatomical and functional characteristics, such as PET-CT and single-photon emission CT (SPECT-CT), whereas more-recent advances and applications have involved the integration of multiple quantitative, functional measurements (for example, multiple PET tracers, varied MRI contrast mechanisms, and PET-MRI), thereby providing a more-comprehensive characterization of the tumour phenotype. The enormous amount of complementary quantitative data generated by such studies is beginning to offer unique insights into opportunities to optimize care for individual patients. Although important technical optimization and improved biological interpretation of multimodality imaging findings are needed, this approach can already be applied informatively in clinical trials of cancer therapeutics using existing tools. These concepts are discussed herein. PMID- 25113845 TI - Quality testing of human albumin by capillary electrophoresis using thermally cross-linked poly(vinyl pyrrolidone)-coated fused-silica capillary. AB - To detect the quality of medicinal human albumin by capillary electrophoresis, we produced a fused-silica capillary coated with thermally cross-linked poly(vinyl pyrrolidone) to prohibit protein adsorption. This type of capillary was easily obtained by injecting an aqueous poly(vinyl pyrrolidone) solution into a fused silica capillary and thermally annealing it at 200 degrees C. Notably, stable and low electro-osmotic flow was obtained in the poly(vinyl pyrrolidone)-coated capillary at pH 2.20-9.00, and the separation of a mixture of four basic proteins indicated that the poly(vinyl pyrrolidone)-coated capillary exhibits excellent repeatability and separation efficiency; moreover, the separation of these four basic proteins could even be achieved at pH 7.00. The protein recovery percentage of human serum albumin in a single-protein solution and a mixed blood proteins solution was determined to be 97.03 and 95.40% in the poly(vinyl pyrrolidone)50-3 (representing the concentration of the capillary-injected poly(vinyl pyrrolidone) aqueous solution, 50 mg/mL, and thermal annealing time, 3 h) capillary, respectively. Based on these results, we used the poly(vinyl pyrrolidone)50-3 coated capillary to quantify the protein content of human albumin, and the results obtained from run to run, day to day and capillary to capillary demonstrated that the coated capillary could be used for quality testing commercially available human albumin. PMID- 25113840 TI - Vessel caliber--a potential MRI biomarker of tumour response in clinical trials. AB - Our understanding of the importance of blood vessels and angiogenesis in cancer has increased considerably over the past decades, and the assessment of tumour vessel calibre and structure has become increasingly important for in vivo monitoring of therapeutic response. The preferred method for in vivo imaging of most solid cancers is MRI, and the concept of vessel-calibre MRI has evolved since its initial inception in the early 1990s. Almost a quarter of a century later, unlike traditional contrast-enhanced MRI techniques, vessel-calibre MRI remains widely inaccessible to the general clinical community. The narrow availability of the technique is, in part, attributable to limited awareness and a lack of imaging standardization. Thus, the role of vessel-calibre MRI in early phase clinical trials remains to be determined. By contrast, regulatory approvals of antiangiogenic agents that are not directly cytotoxic have created an urgent need for clinical trials incorporating advanced imaging analyses, going beyond traditional assessments of tumour volume. To this end, we review the field of vessel-calibre MRI and summarize the emerging evidence supporting the use of this technique to monitor response to anticancer therapy. We also discuss the potential use of this biomarker assessment in clinical imaging trials and highlight relevant avenues for future research. PMID- 25113846 TI - Three dimensional analysis of the composition in solid alloys by variable probe in scanning transmission electron microscopy. AB - This paper reports on a novel approach to quantitatively reconstruct the column by column composition and the 3D distribution of guest atoms inside a host matrix by scanning transmission electron microscopy high angle annular dark field technique. We propose a new mathematical framework that allows to jointly analyze the information from a set of experiments with variable beam convergence and/or defocus. Our scheme allows to reconstruct the atomic distribution along the imaged columns from the measured intensity, for any dependence of the probe intensity on the depth. It is therefore well suited to incorporate channeling effects that are usually neglected in other approaches. As a case study, we focus here on the systematic variation of the beam convergence that permits to set the maximum of the channeling oscillations at different depths. We aim here to define the reliability and the limitation of this technique by the application of the method to accurate dynamic simulations in the case of the InGaN alloy. PMID- 25113844 TI - Transcriptome profiling of CTLs regulated by rapamycin using RNA-Seq. AB - Memory programming of cytotoxic T cells (CTLs) by inflammatory cytokines can be regulated by mammalian target of rapamycin (mTOR). We have shown that inhibition of mTOR during CTL activation leads to the enhancement of memory, but the molecular mechanisms remain largely unknown. Using high-throughput RNA-Seq, we identified genes and functions in mouse CTLs affected by mTOR inhibition through rapamycin. Of the 43,221 identified transcripts, 184 transcripts were differentially expressed after rapamycin treatment, corresponding to 128 annotated genes. Of these genes, 114 were downregulated and only 14 were upregulated. Most importantly, 50 of them are directly related to cell death and survival. In addition, several genes such as CD62L are related to migration. Furthermore, we predicted downregulation of transcriptional regulators based on the total differentially expressed genes, as well as the subset of apoptosis related genes. Quantitative PCR confirmed the differential expressions detected in RNA-Seq. We conclude that the regulatory function of rapamycin may work through inhibition of multiple genes related to apoptosis and migration, which enhance CTL survival into memory. PMID- 25113847 TI - Theoretical modeling of low-energy electronic absorption bands in reduced cobaloximes. AB - The reduced Co(I) states of cobaloximes are powerful nucleophiles that play an important role in the hydrogen-evolving catalytic activity of these species. In this work we analyze the low-energy electronic absorption bands of two cobaloxime systems experimentally and use a variety of density functional theory and molecular orbital ab initio quantum chemical approaches. Overall we find a reasonable qualitative understanding of the electronic excitation spectra of these compounds but show that obtaining quantitative results remains a challenging task. PMID- 25113849 TI - The role of the cytopathologist's interpretation in achieving diagnostic adequacy of head and neck fine needle aspirates. AB - OBJECTIVE: We aimed to assess the potential role of interpretation by cytopathologists on the level of diagnostic adequacy of head and neck fine needle aspirations (FNAs). METHODS: An audit ('first audit') was performed between 1 May 2007 and 30 April 2008 using data from three different hospitals (A, B and C). The specimens were interpreted by two cytopathologists with specific experience in head and neck pathology in hospitals A and B, and by any of the eight cytopathologists (only two of whom were experienced in head and neck cytopathology) in hospital C. Following the analysis of the initial findings, there was a change in practice in hospital C, after which specimens were also read only by two experienced cytopathologists. A new audit ('second audit') was then performed between 20 January 2011 and 20 December 2012 in the same three hospitals. RESULTS: During the first audit, the diagnostic adequacy of FNAs from hospital C was 84.2% compared with 96.6% in hospital A and 97.7% in hospital B (P = 0.000). No significant difference in the diagnostic adequacy rate of the FNAs performed in hospitals A and B was found when comparing the first and second audits. The FNA diagnostic adequacy for hospital C increased significantly in the second relative to the first audit (95.5% versus 84.2%, P = 0.000). CONCLUSIONS: Our study confirms that expert cytology interpretation is important in achieving optimal diagnostic adequacy of head and neck FNAs. PMID- 25113848 TI - Identification of germinal centres in the lymph node of a patient with hyperimmunoglobulin M syndrome associated with congenital rubella. AB - BACKGROUND: The hyper immunoglobulin M syndrome (HIM) associated with congenital rubella infection (rHIM) is an extremely rare disorder, where patients have elevated serum IgM in association with reduced IgG and IgA. We have previously shown that in contrast to X-linked HIM (XHIM), a patient with well-characterised rHIM is able to express functional CD40 ligand, undergo immunoglobulin isotype switching and to generate memory B cells. Here we describe the ultrastructural features of an excised lymph node from this patient. METHODS: An inguinal lymph node was surgically removed and examined histologically as well as by immunohistochemistry. It was then stained with multiple fluorescent dyes to visualize the cellular interactions within the node. Flow cytometry was undertaken on a cellular suspension from the node. FINDINGS: Our patient has normal lymph node architecture by light microscopy. Immunohistochemistry studies showed the presence of scattered germinal centres. Polychromatic immunofluorescence staining showed disruption of the architecture with mostly abnormal germinal centres. A small number of relatively intact germinal centres were identified. Both IgM and IgG bearing cells were identified in germinal centres. INTERPRETATION: In contrast to XHIM where germinal centres are absent, the presence of small numbers of relatively normal germinal centres explain our previous identification of isotype switched memory B cells in rHIM. PMID- 25113850 TI - Diurnal and nocturnal activity budgets of zoo elephants in an outdoor facility. AB - The present study examined the activity budgets of 15 African elephants (1 bull, 6 cows, 2 male juveniles, 2 female juveniles, and 4 male calves) living at the San Diego Zoo Safari Park during the summers of 2010 and 2011. Onsite behavioral data (n = 600 hr) were collected for approximately 12 weeks from 0400 to 0830 and 1100 to 2400 during the 2010 and 2011 summer season. Foraging was the most common behavior state during the day followed by resting, and walking. During the evening hours, the elephants spent majority of their time foraging, resting, and sleeping. The average rate of self-maintenance behavior events (dust, wallow, etc.) increased from 0600 to 0700, 1100 to 1500, and from 1700 to 1900. Positive social behavior events (touch other, play, etc.) remained high from 0500 to 2300, with peaks at 0600, 1300, 1500, and 1900. Negative social events occurred at low rates throughout the day and night, with peaks at 0600, 1900, and 2200. The majority of positive behavior events during the daylight and nighttime hours involved the mother-calf pairs. Furthermore, the calves and juveniles initiated approximately 60% of all social events during the daytime and 57% of all social interactions at night. The results of this study demonstrate the differences between diurnal and nocturnal activity budgets of a multi-age and sex elephant herd in a zoological facility, which highlights the importance of managing elephants to meet their 24 hr behavioral needs. PMID- 25113851 TI - Diagnostic value of the 4Ts score for heparin-induced thrombocytopenia in the critically ill. PMID- 25113852 TI - Finding faces among faces: human faces are located more quickly and accurately than other primate and mammal faces. AB - We tested the specificity of human face search efficiency by examining whether there is a broad window of detection for various face-like stimuli-human and animal faces-or whether own-species faces receive greater attentional allocation. We assessed the strength of the own-species face detection bias by testing whether human faces are located more efficiently than other animal faces, when presented among various other species' faces, in heterogeneous 16-, 36-, and 64 item arrays. Across all array sizes, we found that, controlling for distractor type, human faces were located faster and more accurately than primate and mammal faces, and that, controlling for target type, searches were faster when distractors were human faces compared to animal faces, revealing more efficient processing of human faces regardless of their role as targets or distractors (Experiment 1). Critically, these effects remained when searches were for specific species' faces (human, chimpanzee, otter), ruling out a category-level explanation (Experiment 2). Together, these results suggest that human faces may be processed more efficiently than animal faces, both when task-relevant (targets) and task-irrelevant (distractors), even in direct competition with other faces. These results suggest that there is not a broad window of detection for all face-like patterns but that human adults process own-species' faces more efficiently than other species' faces. Such own-species search efficiencies may arise through experience with own-species faces throughout development or may be privileged early in development, due to the evolutionary importance of conspecifics' faces. PMID- 25113854 TI - Association between non-medical prescription drug use and personality traits among young Swiss men. AB - AIM: To investigate the relationships between six classes of non-medical prescription drug use (NMPDU) and five personality traits. METHODS: Representative baseline data on 5777 Swiss men around 20 years old were taken from the Cohort Study on Substance Use Risk Factors. NMPDU of opioid analgesics, sedatives/sleeping pills, anxiolytics, antidepressants, beta-blockers and stimulants over the previous 12 months was measured. Personality was assessed using the Brief Sensation Seeking Scale; attention deficit-hyperactivity (ADH) using the Adult Attention-Deficit-Hyperactivity Disorder Self-Report Scale; and aggression/hostility, anxiety/neuroticism and sociability using the Zuckerman Kuhlmann Personality Questionnaire. Logistic regression models for each personality trait were fitted, as were seven multiple logistic regression models predicting each NMPDU adjusting for all personality traits and covariates. RESULTS: Around 10.7% of participants reported NMPDU in the last 12 months, with opioid analgesics most prevalent (6.7%), then sedatives/sleeping pills (3.0%), anxiolytics (2.7%), and stimulants (1.9%). Sensation seeking (SS), ADH, aggression/hostility, and anxiety/neuroticism (but not sociability) were significantly positively associated with at least one drug class (OR varied between 1.24, 95%CI: 1.04-1.48 and 1.86, 95%CI: 1.47-2.35). Aggression/hostility, anxiety/neuroticism and ADH were significantly and positively related to almost all NMPDU. Sociability was inversely related to NMPDU of sedatives/sleeping pills and anxiolytics (OR, 0.70; 95%CI: 0.51-0.96 and OR, 0.64; 95%CI: 0.46-0.90, respectively). SS was related only to stimulant use (OR, 1.74; 95%CI: 1.14-2.65). CONCLUSION: People with higher scores for ADH, aggression/hostility and anxiety/neuroticism are at higher risk of NMPDU. Sociability appeared to protect from NMPDU of sedatives/sleeping pills and anxiolytics. PMID- 25113853 TI - Task specificity of attention training: the case of probability cuing. AB - Statistical regularities in our environment enhance perception and modulate the allocation of spatial attention. Surprisingly little is known about how learning induced changes in spatial attention transfer across tasks. In this study, we investigated whether a spatial attentional bias learned in one task transfers to another. Most of the experiments began with a training phase in which a search target was more likely to be located in one quadrant of the screen than in the other quadrants. An attentional bias toward the high-probability quadrant developed during training (probability cuing). In a subsequent, testing phase, the target's location distribution became random. In addition, the training and testing phases were based on different tasks. Probability cuing did not transfer between visual search and a foraging-like task. However, it did transfer between various types of visual search tasks that differed in stimuli and difficulty. These data suggest that different visual search tasks share a common and transferrable learned attentional bias. However, this bias is not shared by high level, decision-making tasks such as foraging. PMID- 25113855 TI - Contemporary sample stacking in analytical electrophoresis. AB - This contribution is a methodological review of the publications about the topic from the last 2 years. Therefore, it is primarily organized according to the methods and procedures used in surveyed papers and the origin and type of sample and specification of analytes form the secondary structure. The introductory part about navigation in the architecture of stacking brings a brief characterization of the various stacking methods, with the description of mutual links to each other and important differences among them. The main body of the article brings a survey of publications organized according to main principles of stacking and then according to the origin and type of the sample. Provided that the paper cited gave explicitly the relevant data, information about the BGE(s) used, procedure, detector employed, and reached LOD and/or concentration effect is given. The papers where the procedure used is a combination of diverse fragments and parts of various stacking techniques are mentioned in a special section on combined techniques. The concluding remarks in the final part of the review evaluate present state of art and the trends of sample stacking in CE. PMID- 25113856 TI - pANCA-vasculitis associated with rectal adenocarcinoma. AB - We report the case of a 69-year-old male patient who was admitted for fever, dry cough, recurrent sinusitis with epistaxis, anorexia with weight loss of 20 kg over a 3-month period, myalgia, and mononeuritis multiplex. He was diagnosed with pANCA/anti-MPO associated vasculitis and rectal adenocarcinoma. The tumor was treated by surgical resection. Recurrence of vasculitis occurred during steroid tapering which prompted us to add Mycophenolate mofetyl. A complete remission was achieved. We conclude that in the present case the vasculitis was an independent disease, not a paraneoplastic phenomenon. We discuss the value of different ANCA serologies for diagnostics and follow-up, the epidemiology of vasculitis associated with malignancy, and the concept of vasculitis as a paraneoplastic syndrome. PMID- 25113857 TI - Silencing the mob: disrupting quorum sensing as a means to fight plant disease. AB - Bacteria are able to sense their population's density through a cell-cell communication system, termed 'quorum sensing' (QS). This system regulates gene expression in response to cell density through the constant production and detection of signalling molecules. These molecules commonly act as auto-inducers through the up-regulation of their own synthesis. Many pathogenic bacteria, including those of plants, rely on this communication system for infection of their hosts. The finding that the countering of QS-disrupting mechanisms exists in many prokaryotic and eukaryotic organisms offers a promising novel method to fight disease. During the last decade, several approaches have been proposed to disrupt QS pathways of phytopathogens, and hence to reduce their virulence. Such studies have had varied success in vivo, but most lend promising support to the idea that QS manipulation could be a potentially effective method to reduce bacterial-mediated plant disease. This review discusses the various QS-disrupting mechanisms found in both bacteria and plants, as well as the different approaches applied artificially to interfere with QS pathways and thus protect plant health. PMID- 25113858 TI - Effect of glucosamine conjugation to zinc(II) complexes of a bis-pyrazole ligand: syntheses, characterization and anticancer activity. AB - The bis(3,5-dimethyl-1H- pyrazol-1yl)acetic acid (bdmpza) ligand was conjugated with tert-butyl-N-(2-aminoethyl) carbonate, methyl-2-amino-4 (methylthio)butanoate and 1,3,4,6-tetra-O-acetyl-beta-d-glucosamine hydrochloride via amide coupling method to form three ligands L1-L3 which were then reacted with Zn(II) salts to form four zinc complexes (1-4). The complexes were characterized by (1)H NMR, (13)C NMR, electrospray ionization mass spectrometry (ESI-MS), FT-IR, CHN analyses. Complexes 1, 2 and 4 were also characterized by single crystal X-ray diffraction. It was found that Zn(II) salts could selectively remove the acetyl group from anomeric position leaving everything else intact. The cytotoxicity studies of the ligand and the complexes showed that the conjugation to acetylated glucosamine enhances cytotoxic ability although the complexes become more hydrophilic. Cytotoxicity studies in human breast adenocarcinoma (MCF-7), human cervical cancer (HeLa WT) and human lung adenocarcinoma (A549) showed that the acetylated glucosamine conjugation to the bis-pyrazole ligated Zn(II) complex led to 2-4 fold increase in cytotoxicity (IC50 values ca. 57-80MUM) against HeLa WT and MCF-7 cell lines. The Zn(II) complex bearing the acetylated glucosamine inhibits the cell cycle in the G2/M phase of MCF-7 cell line. ICP-MS data shows more accumulation of Zn(II) inside the cell upon use of complex 4 as compared to Zn(II) salts or the other presented complexes. Further studies suggest that the mitochondrial transmembrane potential changes in the presence of complex 4 and caspase-7 is activated by Zn(II) salts but the activation is much more by complex 4 and hence there is apoptosis and dose dependent chromatin condensation/nuclear fragmentation as observed by microscopy. PMID- 25113859 TI - CD36 and malaria: friends or foes? A decade of data provides some answers. AB - The past 10 years have generated new insights into the complex interaction between CD36 (cluster of differentiation 36) and malaria. These range from the crystallization of the CD36 homolog, LIMPII (lysosomal integral membrane protein II), permitting modeling of CD36 and its binding to diverse ligands, to cell biology-based studies of CD36 and large population genetic studies assessing the association of CD36 polymorphisms and malarial disease severity. Collectively these lines of evidence indicate that a receptor other than CD36 is associated with severity. CD36 plays an important role in innate immunity and in the phagocytic uptake of multiple pathogens including malaria. CD36 polymorphisms lack association with severity, and isolates that cause severe disease primarily bind to endothelial protein C receptor (EPCR) rather than to CD36. PMID- 25113860 TI - [Cameron ulcers: two clinical presentations of an unusual upper gastrointestinal hemorrhage]. PMID- 25113861 TI - [MALT lymphoma of the gallbladder]. PMID- 25113863 TI - [A trichobezoar causing intestinal obstruction in an adolescent girl]. PMID- 25113862 TI - [Small bowel volvulus: an unusual radiological diagnosis in adults]. PMID- 25113864 TI - Evaluating the physical demands on firefighters using track-type stair descent devices to evacuate mobility-limited occupants from high-rise buildings. AB - The physical demands on firefighting personnel were investigated when using different types of track-type stair descent devices designed for the emergency evacuation of high rise buildings as a function of staircase width and evacuation urgency. Twelve firefighters used five track-type stair descent devices during simulated urgent and non-urgent evacuations. The devices were evaluated under two staircase width conditions (1.12, and 1.32 m), and three devices were also evaluated under a narrower staircase condition (0.91 m). Dependent measures included electromyographic (EMG) data, spine motion, heart rates, Borg Scale ratings, task durations and descent velocities. Stair descent speeds favored the devices that had shorter fore/aft dimensions when moving through the landing. EMG results indicated that there were tradeoffs due to design features, particularly on the landings where the physical demands tended to be greater. On the landings, devices that could be rolled on four wheels reduced the deltoid and bicep activation levels. PMID- 25113865 TI - Surgical management of primary hyperparathyroidism in older adults. AB - OBJECTIVES: To compare the feasibility, safety, and outcome of parathyroidectomy in the management of primary hyperparathyroidism (PHPT) in individuals aged 75 and older with that of those younger than 50. DESIGN: Retrospective chart review. SETTING: Department of Endocrine Surgery, Hospital Paul Desbief (Marseille, France). PARTICIPANTS: Individuals who underwent surgery from June 2005 to February 2013 (N = 526) had a clinical examination and laboratory and imaging assessments to diagnose PHPT. MEASUREMENTS: The clinical and biochemical characteristics and surgery outcomes of individuals younger than 50 (n = 80) were compared with the characteristics and outcomes of those aged 75 and older (n = 89). RESULTS: Most of the participants did not have any specific signs of PHPT, and the diagnosis of PHPT was established in some participants during routine clinical and laboratory examination. Nephrolithiasis and osteitis fibrosa cystica were observed only in the younger group. Urinary calcium decreased with age. Nine participants aged 75 and older did not undergo surgery (four declined, five had medical contraindications). Conventional surgery through transverse cervicotomy was used in the majority of participants. Cure rate was excellent (158/160), with few and reversible minor complications. The coexistence of thyroid lesions was significantly higher in the older (47.5%) than in the younger group (32.3%). Nodules and multinodular goiters were removed in the majority of participants during the parathyroidectomy procedure. CONCLUSION: With the exception of a few cases with severe associated comorbidities, parathyroidectomy is safe and curative and should be considered as first-line choice for older adult with PHPT. PMID- 25113867 TI - [Current recommendations on optic neuritis]. AB - BACKGROUND: The diagnostics and therapy of optic neuritis are complex and require interdisciplinary cooperation. AIM: Compact, up-to-date recommendations for the clinician appear to be desirable. MATERIAL AND METHODS: A selective literature search including the authors' professional experience was carried out. An algorithm for the practical approach to optic neuritis was derived from the best available evidence. RESULTS: Our recommendation distinguishes between compulsory and optional investigations. Differential diagnostic cues with regard to atypical optic neuritis and other optic neuropathies are shown. Standard therapy patterns and means of escalation are suggested. Indications for referral are presented. CONCLUSION: The algorithm suggested in this article provides ophthalmologists with an effective orientation aid for the complete treatment procedure of optic neuritis. PMID- 25113868 TI - Control of the single-molecule magnet behavior of lanthanide-diarylethene photochromic assemblies by irradiation with light. AB - Lanthanide-based extended coordination frameworks showing photocontrolled single molecule magnet (SMM) behavior were prepared by combining highly anisotropic Dy(III) and Ho(III) ions with the carboxylato-functionalized photochromic molecule 1,2-bis(5-carboxyl-2-methyl-3-thienyl)perfluorocyclopentene (H2 dae), which acts as a bridging ligand. As a result, two new compounds of the general formula [{Ln(III) 2 (dae)3 (DMSO)3 (MeOH)}?10 MeOH]n (M=Dy for 1 a and Ho for 2) and two additional pseudo-polymorphs [{Dy(III) 2 (dae)3 (DMSO)3 (H2 O)}?x MeOH]n (1 b) and [{Dy(III) 2 (dae)3 (DMSO)3 (DMSO)}?x MeOH]n (1 c) were obtained. All four compounds have 2D coordination-layer topologies, in which carboxylate bridged Ln2 units are linked together by dae(2-) anions into grid-like frameworks. All four compounds exhibited a strong reversible photochromic response to UV/Vis light. Moreover, both 1 a and 2 show field-induced SMM behavior. The slow magnetic relaxation of 1 a is influenced by the photoisomerization reaction leading to the observation of the cross-effect: photocontrolled SMM behavior. PMID- 25113866 TI - Direct effect of bevacizumab on glioblastoma cell lines in vitro. AB - Bevacizumab is a humanized monoclonal antibody directed against the pro angiogenic factor vascular and endothelial growth factor-A (VEGF-A) used in the treatment of glioblastomas. Although most patients respond initially to this treatment, studies have shown that glioblastomas eventually recur. Several non mutually exclusive theories based on the anti-angiogenic effect of bevacizumab have been proposed to explain these mechanisms of resistance. In this report, we studied whether bevacizumab can act directly on malignant glioblastoma cells. We observe changes in the expression profiles of components of the VEGF/VEGF-R pathway and in the response to a VEGF-A stimulus following bevacizumab treatment. In addition, we show that bevacizumab itself acts on glioblastoma cells by activating the Akt and Erks survival signaling pathways. Bevacizumab also enhances proliferation and invasiveness of glioblastoma cells in hyaluronic acid hydrogel. We propose that the paradoxical effect of bevacizumab on glioblastoma cells could be due to changes in the VEGF-A-dependent autocrine loop as well as in the intracellular survival pathways, leading to the enhancement of tumor aggressiveness. Investigation of how bevacizumab interacts with glioblastoma cells and the resulting downstream signaling pathways will help targeting populations of resistant glioblastoma cells. PMID- 25113869 TI - Outcomes, impact on management, and costs of fungal eye disease consults in a tertiary care setting. AB - OBJECTIVE: To determine the frequency of clinical management changes resulting from inpatient ophthalmic consultations for fungemia and the associated costs. DESIGN: Retrospective case series. PARTICIPANTS: Three hundred forty-eight inpatients at a tertiary care center between 2008 and 2012 with positive fungal blood culture results, 238 of whom underwent an ophthalmologic consultation. METHODS: Inpatient charts of all fungemic patients were reviewed. Costs were standardized to the year 2014. The Student t test was used for all continuous variables and the Pearson chi-square test was used for categorical variables. MAIN OUTCOME MEASURES: Prevalence of ocular involvement, rate of change in clinical management, mortality rate of fungemic patients, and costs of ophthalmic consultation. RESULTS: Twenty-two (9.2%) of 238 consulted patients with fungemia had ocular involvement. Twenty patients had chorioretinitis and 2 had endophthalmitis. Only 9 patients (3.7%) had a change in management because of the ophthalmic consultation. One patient underwent bilateral intravitreal injections. Thirty percent of consulted patients died before discharge or were discharged to hospice. The total cost of new consults was $36 927.54 ($204.19/initial level 5 visit and $138.63/initial level 4). The cost of follow-up visits was $13 655.44 ($104.24/visit). On average, 26.4 patients were evaluated to find 1 patient needing change in management, with an average cost of $5620.33 per change in 1 patient's management. CONCLUSIONS: Clinical management changes resulting from ophthalmic consultation in fungemic patients were uncommon. Associated costs were high for these consults in a patient population with a high mortality rate. Together, these data suggest that the usefulness of routine ophthalmic consultations for all fungemic patients is likely to be low. PMID- 25113871 TI - Comprehensive two-dimensional liquid chromatographic analysis of anthocyanins. AB - Anthocyanins are naturally occurring plant pigments whose accurate analysis is hampered by their complexity and unique chromatographic behaviour associated with on-column conversion reactions. This paper reports the evaluation of off-line comprehensive two-dimensional liquid chromatography (LC*LC) for the analysis of anthocyanins. Hydrophilic interaction chromatography (HILIC) was used in the first dimension in combination with reversed phase liquid chromatography (RP-LC) in the second dimension. For the selective detection of anthocyanins, diode array detection was used, while high resolution quadrupole-time-of-flight mass spectrometry (Q-TOF) was used for compound identification. As application, the HILIC*RP-LC separation of diverse anthocyanins in blueberries, red radish, black beans, red grape skins and red cabbage is demonstrated. Off-line HILIC*RP-LC revealed information which could not be obtained by one-dimensional HPLC methods, while the structured elution order for the anthocyanins simplifies compound identification and facilitates the comparison of anthocyanin content of natural products by means of contour plots. PMID- 25113870 TI - Walking deficits and centrophobism in an alpha-synuclein fly model of Parkinson's disease. AB - Parkinson's disease (PD) is a movement neurodegenerative disorder, characterized by bradykinesia, rigidity and tremor, constituting difficulties in walking and abnormal gait. Previous research shows that Drosophila expressing human alpha synuclein A30P (A30P) develop deficits in geotaxis climbing; however, geotaxis climbing is a different movement modality from walking. Whether A30P flies would exhibit abnormal walking in a horizontal plane, a measure more relevant to PD, is not known. In this study, we characterized A30P fly walking using a high-speed camera and an automatic behavior tracking system. We found that old but not young A30P flies exhibited walking abnormalities, specifically decreased total moving distance, distance per movement, velocity, angular velocity and others, compared with old control flies. Those features match the definition of bradykinesia. Multivariate analysis further suggested a synergistic effect of aging and A30P, resulting in a distinct pattern of walking deficits, as seen in aged A30P flies. Psychiatric problems are common in PD patients with anxiety affecting 40-69% of patients. Central avoidance is one assessment of anxiety in various animal models. We found old but not young A30P flies exhibited increased centrophobism, suggesting possible elevated anxiety. Here, we report the first quantitative measures of walking qualities in a PD fly model and propose an alternative behavior paradigm for evaluating motor functions apart from climbing assay. PMID- 25113872 TI - In situ derivatization combined to automated microextraction by packed sorbents for the determination of chlorophenols in soil samples by gas chromatography mass spectrometry. AB - A method based on the coupling of in situ extraction and derivatization of chlorophenols (CPs) (2-chlorophenol, 4-chloro-3-methylphenol, 2,4-dichlorophenol, and 2,4,6-trichlorophenol) from soils, accomplishing their preconcentration by means of automated microextraction by packed sorbent (MEPS), is proposed. After extraction and acylation of the chlorophenols in aqueous medium, the liquid phase obtained is subjected to the MEPS procedure. The QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) and MEPS techniques were compared and the results confirmed the preconcentration carried out with MEPS. The existence of a matrix effect was checked and the analytical characteristics of the method were determined in a soil sample. The method provided good linearity (from 1 to 12MUgkg(-1)), together with good repeatability and reproducibility values (RSD equal to or less than 10%). The limits of detection were in the 0.118-0.894MUgkg( 1) range. A certified reference material was applied to validate the proposed methodology. PMID- 25113873 TI - Optimum pH for the determination of bisphenols and their corresponding diglycidyl ethers by gas chromatography-mass spectrometry. Migration kinetics of bisphenol A from polycarbonate glasses. AB - This paper presents, on the one hand, the study of the influence of the pH of the medium on the determination of bisphenol F (BPF), bisphenol A (BPA) and their corresponding diglycidyl ethers (BFDGE and BADGE, respectively) by GC-MS after a solid-phase extraction step, using BPA-d16 as internal standard and Parallel Factor Analysis (PARAFAC) decomposition as a multi-way tool for the unequivocal identification and quantification of the four analytes. As the structure of both BFDGE and BADGE has two 2,3-epoxypropoxy groups that can undergo an acid- or base catalyzed ring-opening via nucleophilic substitution reactions, several samples spiked with the four analytes were set to different pH values between 2 and 12. The best results were obtained in the pH region 8-10, being 9 the most suitable value. Coelution of interferents was overcome using the PARAFAC decomposition; otherwise, the presence of some analytes could not have been ensured according to the regulations currently in force. Secondly, the release of BPA from polycarbonate glasses into food simulant D1 (ethanol 50% (v/v)) over time was studied through seven migration tests and the differences found in this migration process with the incubation temperature (50 and 70 degrees C) were evaluated. A nonlinear regression was used to fit the experimental data following an exponential relation between the concentration of BPA transferred from every glass and the respective migration test. None of the quantities of BPA released exceeded the specific migration limit of 0.6mgkg(-1) laid down for this compound in the Commission Regulation (EU) No 10/2011, so the compliance of the glasses evaluated was ensured. The average recovery percentages of the four analytes at a fortification level of 800ngL(-1) ranged from 50.14 to 92.75%. The detection capability (CCbeta) of the method for BPA was 2.60MUgL(-1) for n=2 replicates, with probabilities of false positive and false negative fixed at 0.05. PMID- 25113874 TI - Photoactivated cytotoxicity of ferrocenyl-terpyridine oxovanadium(IV) complexes of curcuminoids. AB - Oxovanadium(IV) complexes, viz. [VO(Fc-tpy)(Curc)](ClO4) (1), [VO(Fc tpy)(bDHC)](ClO4) (2), [VO(Fc-tpy)(bDMC)](ClO4) (3) and [VO(Ph-tpy)(Curc)](ClO4) (4), of 4'-ferrocenyl-2,2':6',2"-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2" terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC) and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo induced DNA cleavage activity and photocytotoxicity in visible light studied. The ferrocenyl complexes 1-3 showed an intense metal-to-ligand charge transfer band near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near 0.65 V and -1.05 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to calf thymus DNA showed significant photocleavage of plasmid DNA in red light of 647 nm forming OH radicals. The complexes showed photocytotoxicity in HeLa and Hep G2 cancer cells in visible light of 400-700 nm with low dark toxicity. ICP-MS and fluorescence microscopic studies exhibited significant cellular uptake of the complexes within 4 h of treatment with complexes. The treatment with complex 1 resulted in the formation of reactive oxygen species inside the HeLa cells which was evidenced from the DCFDA assay. PMID- 25113875 TI - Indole-3-ethylsulfamoylphenylacrylamides: potent histone deacetylase inhibitors with anti-inflammatory activity. AB - A series of 2-methyl-1H-indol-3-ethylsulfamoylphenylacrylamides based on LBH589 PXD101 core have been synthesized and evaluated for their histone deacetylase (HDAC) inhibitory and anti-inflammatory activity. In vitro, compounds 9-12 show 2.6-fold better HDAC inhibition and 3-fold better IL-6 suppression compared to LBH589.HCl (1.HCl). Furthermore, these compounds did not show apparent cell viability suppression on macrophages while in contrast, treatment with 1.HCl resulted in significant reduction in cell viability as demonstrated by an MTT assay. Repressed expression of iNOS, COX-2 and reduced phosphorylation of p65 revealed the inhibitory effect of these analogues on inflammatory mediator release which is related to inhibited NF-KB signals. (N-Hydroxy-3-{3-[2-(2-methyl 1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide) (9), exhibited ability superior to that of 1.HCl, was able to reduce carrageenan-induced acute inflammation in an animal model. Compounds 9-12 have potential anti-inflammatory activity and compound 9 can serve as lead compound for further development. PMID- 25113876 TI - Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds. AB - RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to phthalazine moiety. Similarly, our strategy in this research depends on the interconnection between some sulfa drugs and certain phthalazin-1(2H)-one scaffolds in an attempt to enhance their antibacterial activity. This approach was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through amide linkers 6a, b to produce the target compounds 10a-d and 15a-e, respectively. The antibacterial activity of the newly synthesized compounds showed that all tested compounds have antibacterial activity higher than that of their reference sulfa drugs 1a-c. Compound 10c represented the highest antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and Staphylococcus aureus with MIC = 0.39 MUmol/mL. Moreover, compound 10d displayed excellent antibacterial activity against Gram-negative bacteria Escherichia coli and Salmonella typhimurium with MIC = 0.39 and 0.78 MUmol/mL, respectively. PMID- 25113877 TI - Design, synthesis and biological evaluation of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives as potent anticancer agents. AB - A series of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives were designed, synthesized and evaluated for in vitro anticancer activity against four selected human cancer cell lines (nasopharyngeal neoplasm CNE, liver cancer BEL-7402, gastric cancer MGC-803, lung adenocarcinoma A549). Most of the synthesized compounds exhibit effective cytotoxic activity against the four tested cancer cell lines with the IC50 values at micromolar concentration level. Some preliminary structure-activity relationships were also discussed. In this series of derivatives, compound 3g shows excellent broad spectrum anticancer activity with IC50 values ranging from 3.57 to 20.07 MUM. The in vitro anticancer activity effect and action mechanism of compound 3g on human gastric carcinoma MGC-803 cell were further investigated. The results showed that compound 3g exhibits dose and time-dependent anticancer effects on MGC-803 cells through apoptosis, which might be associated with its decreasing intracellular calcium and the mitochondrial membrane potential. PMID- 25113878 TI - Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents. AB - Cancer multidrug resistance (MDR) is a common cause of treatment failure in cancer patients. Increased expression of permeability glycoprotein (P-gp), which is also known as MDR-1, is the main cause of multidrug resistance. Podophyllotoxin derivatives hold great promise in the battle to overcome multidrug resistance, as they can induce cytotoxicity through multiple mechanisms. Here, we synthesized sixteen novel podophyllotoxin derivatives and evaluated their cytotoxicities in human cancer cell lines, HeLa, K562 and K562/A02. Some of these compounds were more potent than etoposide, a clinically relevant inhibitor of DNA repair enzymes. In particular, compound 5p exhibited the most potent activity toward drug-resistant K562/A02 cells, as it robustly inhibited tumor cell proliferation and induced apoptosis. Furthermore, preliminary investigation suggested that 5p inhibited the expression of MDR-1 in K562/A02 cells more effectively than etoposide. PMID- 25113879 TI - Synthesis and bioevaluation of 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic acids as potent xanthine oxidase inhibitors. AB - A series of 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic acid derivatives (8a-f, 9a-m) were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro. Structure-activity relationship analyses have also been presented. Most of the target compounds exhibited potency levels in the nanomolar range. Compound 9e emerged as the most potent xanthine oxidase inhibitor (IC50 = 5.5 nM) in comparison to febuxostat (IC50 = 18.6 nM). Steady-state kinetics measurements with the bovine milk enzyme indicated a mixed type inhibition with Ki and Ki' values of 0.9 and 2.3 nM, respectively. A molecular modeling study on compounds 9e was performed to gain an insight into its binding mode with xanthine oxidase, and to provide the basis for further structure-guided design of new non purine xanthine oxidase inhibitors related with 2-phenyl-4-methyl-1,3-selenazole 5-carboxylic acid scaffold. PMID- 25113881 TI - Experimental and economical evaluation of bioconversion of forest residues to biogas using organosolv pretreatment. AB - The methane potential of forest residues was compared after applying organic solvent, i.e., acetic acid, ethanol, and methanol pretreatments using batch anaerobic digestion (AD). The pretreatments were performed at 190 degrees C with 50% (V/V) organic solvent for 60 min. The accumulated methane yields after 40 days of AD from pretreated forest residues were between 0.23 and 0.34 m(3) CH4/kg VS, which shows a significant improvement compared to 0.05 m(3) CH4/kg VS, from untreated forest residues. These improvements count up to 50% increase in the methane yields from the pretreated substrates based on expected theoretical yield from carbohydrates. Among the organic solvents, pretreatments with acetic acid and ethanol led to highest methane yields, i.e., over 0.30 m(3) CH4/kg VS. However, techno-economical evaluation showed, pretreatment with methanol was more viable financially. The capital investments of the plant operating 20,000 tons of forest residues varied between 56 and 60 million USD, which could be recovered in less than 8 years of operation. PMID- 25113882 TI - Effect of liquefaction temperature on hydroxyl groups of bio-oil from loblolly pine (Pinus taeda). AB - Loblolly pine was liquefied with ethylene glycol at 100, 150, 200 and 250 degrees C in order to analyze the effect of liquefaction temperature on hydroxyl groups of bio-oil, and to determine the source and variation of hydroxyl groups. The optimum temperature was found to be 150-200 degrees C. Hydroxyl number (OHN) of the bio-oil was ranged from 632 to 1430 mg KOH/g. GC-MS analysis showed that 70-90% of OHN was generated from unreacted EG. (31)P NMR analysis showed that the majority of hydroxyl groups were aliphatic, and none of the bio-oil exhibited any detectable hydroxyl groups from phenolic sources. Finally, it was found that all bio-oils were stable in terms of OHN for 2 months when stored at -10 degrees C. PMID- 25113883 TI - Fast pyrolysis product distribution of biopretreated corn stalk by methanogen. AB - After pretreated by methanogen for 5, 15 and 25 days, corn stalk (CS) were pyrolyzed at 250, 300, 350, 400, 450 and 500 degrees C by Py-GC/MS and product distribution in bio-oil was analyzed. Results indicated that methanogen pretreatment changed considerably the product distribution: the contents of sugar and phenols increased; the contents of linear carbonyls and furans decreased; the contents of linear ketones and linear acids changed slightly. Methanogen pretreatment improved significantly the pyrolysis selectivity of CS to phenols especially 4-VP. At 250 degrees C, the phenols content increased from 42.25% for untreated CS to 79.32% for biopretreated CS for 5 days; the 4-VP content increased from 28.6% to 60.9%. Increasing temperature was contributed to convert more lignin into 4-VP, but decreased its content in bio-oil due to more other chemicals formed. The effects of biopretreatment time on the chemicals contents were insignificant. PMID- 25113884 TI - Cationic polymers for successful flocculation of marine microalgae. AB - Flocculation of microalgae is a promising technique to reduce the costs and energy required for harvesting microalgae. Harvesting marine microalgae requires suitable flocculants to induce the flocculation under marine conditions. This study demonstrates that cationic polymeric flocculants can be used to harvest marine microalgae. Different organic flocculants were tested to flocculate Phaeodactylum tricornutum and Neochloris oleoabundans grown under marine conditions. Addition of 10 ppm of the commercial available flocculants Zetag 7557 and Synthofloc 5080H to P. tricornutum showed a recovery of, respectively, 98% +/ 2.0 and 94% +/- 2.9 after flocculation followed by 2h sedimentation. Using the same flocculants and dosage for harvesting N. oleoabundans resulted in a recovery of 52% +/- 1.5 and 36% +/- 11.3. This study shows that cationic polymeric flocculants are a viable option to pre-concentrate marine cultivated microalgae via flocculation prior to further dewatering. PMID- 25113886 TI - Identification and analysis of ADP-ribosylated proteins. AB - The analysis of ADP-ribosylated proteins is a challenging task, on the one hand because of the diversity of the target proteins and the modification sites, on the other hand because of the particular problems posed by the analysis of ADP ribosylated peptides. ADP-ribosylated proteins can be detected in in vitro experiments after the incorporation of radioactively labeled or chemically modified ADP-ribose. Endogenously ADP-ribosylated proteins may be detected and enriched by antibodies directed against the ADP-ribosyl moiety or by ADP-ribosyl binding macro domains. The determination of the exact attachment site of the modification, which is a prerequisite for the understanding of the specificity of the various ADP-ribosyl transferases and the structural consequences of ADP ribosylation, necessitates the proteolytic cleavage of the proteins. The resulting peptides can afterwards be enriched either by IMAC (using the affinity of the pyrophosphate group for heavy metal ions) or by immobilized boronic acid beads (using the affinity of the vicinal ribose hydroxy groups for boronic acid). The identification of the modified peptides usually requires tandem mass spectrometric measurements. Problems that hamper the mass spectrometric analysis by collision-induced decay (CID) can be circumvented either by the application of different fragmentation techniques (electron transfer or electron capture dissociation; ETD or ECD) or by enzymatic cleavage of the ADP-ribosyl group to ribosyl-phosphate. PMID- 25113887 TI - Will new insights into neural networks help us improve our models of suicidal behavior? PMID- 25113885 TI - Combination of glucosamine and low-dose cyclosporine for atopic dermatitis treatment: a randomized, placebo-controlled, double-blind, parallel clinical trial. AB - Our recent pilot study showed better outcomes using a combination of low-dose cyclosporine and glucosamine than cyclosporine alone in the treatment of atopic dermatitis (AD). Here, a randomized, placebo-controlled, double-blind, parallel designed study was planned to compare the efficacy and safety of low-dose cyclosporine and glucosamine combination to low-dose cyclosporine alone for the treatment of patients with moderate to severe AD. AD patients with a Severity Scoring of Atopic Dermatitis (SCORAD) index >= 30 were randomly assigned in a 1:1 ratio to receive either cyclosporine 2 mg/kg and glucosamine 25 mg/kg (group A) or cyclosporine and placebo (group B) for 8 weeks. SCORAD indices, serum levels of chemokine ligand 17 and interleukin-31, eosinophil counts, and blood cyclosporine levels were examined before and after treatment. The SCORAD indices for group A (n = 19) were significantly reduced after the treatment and a significant correlation between the changes in the SCORAD indices and changes in the serum levels of chemokine ligand 17, but not interleukin-31, was detected. Glucosamine combined with cyclosporine did not increase adverse events and serum cyclosporine levels compared with cyclosporine alone. Therefore, combination of low-dose cyclosporine and glucosamine may be useful to allow the long-term use of cyclosporine in the treatment of patients with moderate to severe AD. PMID- 25113888 TI - Exploring prospective predictors of completed suicides: evidence from the general social survey. AB - BACKGROUND: This study was based on over 30,000 respondents who completed General Social Surveys between 1978 and 2002. AIMS: We approached these respondents prospectively, comparing and contrasting the responses of those who subsequently died by suicide (N = 141) with those who died from all other causes (N = 9,115). METHOD: We employed chi-square and logistic regression analyses of important demographic confounders to test for statistically significant differences between suicide decedents and all other decedents. RESULTS: Suicide decedents died on average 2 years sooner than all other decedents. When covariates of age and gender were applied, suicide decedents exhibited greater acceptance of suicide for dealing with various adverse life circumstances, were more likely to have been the gun owners in their households, lived in regions where gun ownership was more commonplace, and held less strong religious beliefs and less of a belief of an afterlife. CONCLUSION: The observed affinity between attitudes of suicide acceptability and completed suicide suggests a potential for creating a meaningful assessment tool to identify those positioned at the extreme end of the suicide risk continuum. PMID- 25113889 TI - The rate of fatality and demographic characteristics associated with various suicide methods: a community-based study in Northern Taiwan. AB - BACKGROUND: Understanding lethality and risk factors of suicide methods is an initial step in suicide prevention. AIMS: To investigate the fatality rate and demographic characteristics of various suicide methods. METHOD: This study enrolled consecutive individuals with episodes of suicide attempts registered in a surveillance database in a city with a high rate of suicide mortality in Taiwan, from January 1, 2006, to December 31, 2010. In total, 3,089 suicide attempt events (including 2,583 nonfatal suicides and 506 completed suicides) occurred during the study period. RESULTS: Overall, the fatality rate of suicides was 16.4%. Charcoal burning accounted for the most suicide deaths (37.6%), with a fatality rate of 50.1%. Suicide by hanging carried the highest fatality rate (81.2%). Males tended to choose more lethal methods and had higher fatality rates compared with females. Elders and married persons were less likely to attempt suicide by charcoal burning. The case fatality ratio increased along with age among suicide attempts, but not in those using charcoal burning. CONCLUSION: The choice of suicide methods and lethality might be influenced by one's demographic characteristics. RESULTS from this study may provide clues for establishing suicide prevention strategies such as restricting access to common lethal suicide methods in the high-risk group. PMID- 25113890 TI - Shadows from the past: the situated meaning of being suicidal among depressed older people living in the community. AB - BACKGROUND: Most depressed older people in a suicidal state have mixed feelings, where the wish to live and the wish to die wage a battle. AIMS: To explore and describe depressed older people's experiences of being suicidal and their search for meaning. METHOD: Data were collected from 29 participants resident in the Rogaland and Vestfold districts of Norway, by means of individual interviews, after which a thematic analysis was performed. RESULTS: For the participants in this study, the lived experiences of the situated meaning of survival after being suicidal comprised a main theme - "shadows from the past" - and two themes - "feeling that something inside is broken" and "a struggle to catch the light." CONCLUSION: Mental health-care professionals might be able to reduce the risk of suicide and perturbation by helping depressed older people to explore, resolve, and ultimately come to terms with their unresolved historical issues. Additional valuable strategies in primary care settings include encountering patients frequently, monitoring adherence to care plans, and providing support to address the source of emotional pain and distress. PMID- 25113891 TI - Ethnic differences in self-poisoning across South London. AB - BACKGROUND: Self-poisoning (overdose) is the commonest form of self-harm cases presenting to acute secondary care services in the UK, where there has been limited investigation of self-harm in black and minority ethnic communities. London has the UK's most ethnically diverse areas but presents challenges in resident-based data collection due to the large number of hospitals. AIMS: To investigate the rates and characteristics of self-poisoning presentations in two central London boroughs. METHOD: All incident cases of self-poisoning presentations of residents of Lambeth and Southwark were identified over a 12 month period through comprehensive acute and mental health trust data collection systems at multiple hospitals. Analysis was done using STATA 12.1. RESULTS: A rate of 121.4/100,000 was recorded across a population of more than half a million residents. Women exceeded men in all measured ethnic groups. Black women presented 1.5 times more than white women. Gender ratios within ethnicities were marked. Among those aged younger than 24 years, black women were almost 7 times more likely to present than black men were. CONCLUSION: Self-poisoning is the commonest form of self-harm presentation to UK hospitals but population-based rates are rare. These results have implications for formulating and managing risk in clinical services for both minority ethnic women and men. PMID- 25113892 TI - History of suicide attempts in adults with Asperger syndrome. AB - BACKGROUND: Individuals with Asperger syndrome (AS) may be at higher risk for attempting suicide compared to the general population. AIMS: This study examines the issue of suicidality in adults with AS. METHOD: An online survey was completed by 50 adults from across Ontario. The sample was dichotomized into individuals who had attempted suicide (n = 18) and those who had not (n = 32). We examined the relationship between predictor variables and previous attempts, and compared the services that both groups are currently receiving. RESULTS: Over 35% of individuals with AS reported that they had attempted suicide in the past. Individuals who attempted suicide were more likely to have a history of depression and self-reported more severe autism symptomatology. Those with and without a suicidal history did not differ in terms of the services they were currently receiving. This study looks at predictors retrospectively and cannot ascertain how long ago the attempt was made. Although efforts were made to obtain a representative sample, there is the possibility that the individuals surveyed may be more or less distressed than the general population with AS. CONCLUSION: The suicide attempt rate in our sample is much higher than the 4.6% lifetime prevalence seen in the general population. These findings highlight a need for more specialized services to help prevent future attempts and to support this vulnerable group. PMID- 25113893 TI - Lipophilic statin use and suicidal ideation in a sample of adults with mood disorders. AB - BACKGROUND: Mood disorders are associated with a high risk of suicide. Statin therapy has been implicated in this relationship. AIMS: To further clarify reported associations between suicide and cholesterol in mental health conditions, we conducted an analysis of dietary, clinical, and suicidal ideation measures in community-living adults with mood disorders. METHOD: Data were used from a cross-sectional study of a randomly selected community-based sample (> 18 years; n = 97) with verified mood disorders. Dietary (e.g., fat, iron, vitamin intakes), clinical (e.g., current depression and mania symptoms, medications), and sociodemographic (age, sex, and income) measures were analyzed using bivariate statistics and Poisson regression with robust variance. RESULTS: Participants were predominantly female (71.1%) with bipolar disorder (59.8%); almost one-third (28.9%) were taking lipophilic statins. The prevalence of suicidal ideation was more than 2.5 times in those taking statins, PR = 2.59, 95% CI 1.27-5.31, p < .05. The prevalence ratio for suicidal ideation was 1.10, 95% CI 1.06-1.15, p < .001, for each unit increase in mania symptom scores. No associations between suicidal ideation and dietary intake measures were identified. CONCLUSION: Individuals with mood disorders may be susceptible to neuropsychiatric effects of cholesterol-lowering drugs, which warrants further research. PMID- 25113897 TI - Improving prediction of binge episodes by modelling chronicity of dietary restriction. AB - This study evaluates the influences of chronicity of, and time lag between, dietary restriction and binge outcome for predicting binge episode onset. Sixty two women aged 18 to 40 years old completed an online survey at random intervals seven times daily for a 7-day period. Participants self-reported engagement in dietary restriction and/or binging, and temptation to binge. Consecutive instances of reported dietary restriction better predicted subsequent binges than single instances. As the time lag between the first report of dietary restriction and binge onset increased, a clear linear trend emerged, such that the value of restriction for predicting binges increased with the number of consecutive assessments in which they reported dietary restriction. A similar pattern was found when predicting temptation to binge. Present findings suggest that duration of restriction is a crucial determinant of binge onset. These findings have implications for clinical practice by highlighting the time course from dietary restriction to binging. PMID- 25113896 TI - Influence of RNA extraction methods and library selection schemes on RNA-seq data. AB - BACKGROUND: Gene expression analysis by RNA sequencing is now widely used in a number of applications surveying the whole transcriptomes of cells and tissues. The recent introduction of ribosomal RNA depletion protocols, such as RiboZero, has extended the view of the polyadenylated transcriptome to the poly(A)- fraction of the RNA. However, substantial amounts of intronic transcriptional activity has been reported in RiboZero protocols, raising issues regarding their potential nuclear origin and the impact on the actual sequence depth in exonic regions. RESULTS: Using HEK293 human cells as source material, we assessed here the impact of the two commonly used RNA extraction methods and of the library construction protocols (rRNA depletion versus mRNA) on 1) the relative abundance of intronic reads and 2) on the estimation of gene expression values. We benchmarked the rRNA depletion-based sequencing with a specific analysis of the cytoplasmic and nuclear transcriptome fractions, suggesting that the large majority of the intronic reads correspond to unprocessed nuclear transcripts rather than to independent transcriptional units. We show that Qiagen or TRIzol extraction methods retain differentially nuclear RNA species, and that consequently, rRNA depletion-based RNA sequencing protocols are particularly sensitive to the extraction methods. CONCLUSIONS: We could show that the combination of Trizol-based RNA extraction with rRNA depletion sequencing protocols led to the largest fraction of intronic reads, after the sequencing of the nuclear transcriptome. We discuss here the impact of the various strategies on gene expression and alternative splicing estimation measures. Further, we propose guidelines and a double selection strategy for minimizing the expression biases, without loss of information. PMID- 25113899 TI - Temporal trends in non-stricturing and non-penetrating behaviour at diagnosis of Crohn's disease in Orebro, Sweden: a population-based retrospective study. AB - BACKGROUND AND AIM: The incidence of Crohn's disease (CD) is continuing to rise in several countries and in others it appears to have already levelled off after a period of increase. We updated our previous population-based study, by re extraction of all information on patients diagnosed with CD between 1963 and 2010. Our aim was to assess temporal trends in incidence, prevalence and disease phenotype at diagnosis. METHODS: Patients of all ages with a potential diagnosis of CD were identified retrospectively by evaluation of medical notes of all current and previous patients at the colitis clinic, Orebro University Hospital amended by computerised search in the inpatient, outpatient, primary care and histopathological records. Diagnosis was confirmed by subsequent evaluation of medical notes. Disease phenotype was defined according to the Montreal classification. RESULTS: The incidence increased over time, especially among Crohn's disease, A1 and A3. SaTScan model revealed a statistically significant high incidence during 1991-2010 (p=0.0001). The median age at diagnosis increased from 28 (3-79) years to 37 (5-87) years (p=0.0002). The point prevalence increased from 21/10(5) (14-32) in 1965 to 267/10(5) (244-291) in 2010. Non stricturing and non-penetrating disease at diagnosis increased from 12.5% in 1963 1965 to 82.3% in 2006-2010 (p<0.0001). CONCLUSION: The incidence of CD increased over time, although it seemed to be plateauing during the most recent decades. A striking increase in non-stricturing, non-penetrating disease at diagnosis was observed, suggesting earlier diagnosis or phenotypic change. The observed point prevalence in 2010 is among the highest reported. PMID- 25113900 TI - Kinetic analysis of mechanochemical chain scission of linear poly(phthalaldehyde). AB - The kinetics of mechanochemical chain scission of poly(phthalaldehyde) (PPA) are investigated. Ultrasound-induced cavitation is capable of causing chain scission in the PPA backbone that ultimately leads to rapid depolymerization of each resulting polymer fragment when above the polymer's ceiling temperature (Tc ). An interesting feature of the mechanochemical breakdown of PPA is that "half-chain" daughter fragments are not observed, since the depolymerization is rapid following chain scission. These features facilitate the determination of rate constants of activation for multiple molecular weights from a single sonication experiment. Additionally, the degradation kinetics are modified with chain-end trapping agents through variation of the nature and amount of small molecule nucleophile or electrophile. PMID- 25113901 TI - Early bovine embryos regulate oviduct epithelial cell gene expression during in vitro co-culture. AB - In mammals, the oviduct may participate to the regulation of early embryo development. In vitro co-culture of early bovine embryos with bovine oviduct epithelial cells (BOEC) has been largely used to mimic the maternal environment. However, the mechanisms of BOEC action have not been clearly elucidated yet. The aim of this study was to determine the response of BOEC cultures to the presence of developing bovine embryos. A 21,581-element bovine oligonucleotide array was used compare the gene expression profiles of confluent BOEC cultured for 8 days with or without embryos. This study revealed 34 differentially expressed genes (DEG). Of these 34 genes, IFI6, ISG15, MX1, IFI27, IFI44, RSAD2, IFITM1, EPSTI1, USP18, IFIT5, and STAT1 expression increased to the greatest extent due to the presence of embryos with a major impact on antiviral and immune response. Among the mRNAs at least 25 are already described as induced by interferons. In addition, transcript levels of new candidate genes involved in the regulation of transcription, modulation of the maternal immune system and endometrial remodeling were found to be increased. We selected 7 genes and confirmed their differential expression by quantitative RT-PCR. The immunofluorescence imaging of cellular localization of STAT1 protein in BOEC showed a nuclear translocation in the presence of embryos, suggesting the activation of interferon signaling pathway. This first systematic study of BOEC transcriptome changes in response to the presence of embryos in cattle provides some evidences that these cells are able to adapt their transcriptomic profile in response to embryo signaling. PMID- 25113898 TI - Patient and physician views on the quality of care in inflammatory bowel disease: results from SOLUTION-1, a prospective IG-IBD study. AB - INTRODUCTION: Remarkable differences in quality of care (QoC) might be observed in different countries, affecting quality of life of inflammatory bowel disease (IBD) patients. The aim of this study was to assess patient and physician perceptions of the QoC in Italy. METHODS: A multicentre observational study on the quality of care in IBD (SOLUTION-1) was conducted in 36 IG-IBD (Italian Group for Inflammatory Bowel Disease) centres in Italy. The QUOTE-IBD (Quality of Care Through the Patient's Eyes) questionnaire was administered to IBD patients and to the attending physicians. The Quality Impact (QI) score summarises the QUOTE-IBD questionnaire, and a QI >9 is considered satisfactory. RESULTS: Nine-hundred ninety-two patients and 75 physicians completed the QUOTE-IBD questionnaire. The patients scored the domains of competence (9.47 vs. 8.55) and costs (9.54 vs. 8.26) higher that the physicians, while information (9.31 vs. 9.43) and continuity of care (8.40 vs. 9.01) were scored lower. The QI score was rated worse by physicians with less experience (<12 years) with regard to competence (8.0 vs. 9.01), courtesy (8.12 vs. 10.0) and autonomy (8.97 vs. 10.0). Physicians considered the cost domain unsatisfactory. CONCLUSIONS: Healthcare was rated as satisfactory overall for Italian patients and physicians. The physicians underestimate their competence and consider the cost of medical management unsatisfactory. The patients are more critical regarding the continuity of care and information. Country-specific data on QoC allow local governments to allocate resources more effectively. PMID- 25113904 TI - Patchwork structure-function analysis of the Sendai virus matrix protein. AB - Paramyxoviruses contain a bi-lipidic envelope decorated by two transmembrane glycoproteins and carpeted on the inner surface with a layer of matrix proteins (M), thought to bridge the glycoproteins with the viral nucleocapsids. To characterize M structure-function features, a set of M domains were mutated or deleted. The genes encoding these modified M were incorporated into recombinant Sendai viruses and expressed as supplemental proteins. Using a method of integrated suppression complementation system (ISCS), the functions of these M mutants were analyzed in the context of the infection. Cellular membrane association, localization at the cell periphery, nucleocapsid binding, cellular protein interactions and promotion of viral particle formation were characterized in relation with the mutations. At the end, lack of nucleocapsid binding go together with lack of cell surface localization and both features definitely correlate with loss of M global function estimated by viral particle production. PMID- 25113902 TI - Marital conflict in early childhood and adolescent disordered eating: emotional insecurity about the marital relationship as an explanatory mechanism. AB - Disordered eating behaviors, including frequent dieting, unhealthy weight control behaviors (e.g., vomiting and skipping meals for weight loss) and binge eating are prevalent among adolescents. While negative, conflict-ridden family environments have long been implicated as problematic and a contributing factor to the development of disordered eating, few studies have examined the influence of marital conflict exposure in childhood to understand the development of these behaviors in adolescence. The current study investigates the impact of marital conflict, children's emotional insecurity about the marital relationship, and disordered eating behaviors in early adolescence in a prospective, longitudinal study of a community sample of 236 families in Midwest and Northeast regions of the U.S. Full structural mediation analyses utilizing robust latent constructs of marital conflict and emotional insecurity about the marital relationship, support children's emotional insecurity as an explanatory mechanism for the influence of marital conflict on adolescent disordered eating behaviors. Findings are discussed with important implications for the long-term impact of marital conflict and the development of disordered eating in adolescence. PMID- 25113905 TI - Functional characterization of Autographa californica multiple nucleopolyhedrovirus gp16 (ac130). AB - To investigate the function of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) gp16, multiple gp16-knockout and repair mutants were constructed and characterized. No obvious difference in productivity of budded virus, DNA synthesis, late gene expression and morphogenesis was observed between gp16-knockout and repair viruses, but gp16 deletion resulted in six hours of lengthening in ST50 to the third instar Spodoptera exigua larvae in bioassays. GP16 was fractionated mainly in the light membrane fraction, by subcellular fractionation. A GP16-EGFP fusion protein was predominantly localized close around the nuclear membrane in infected cells, being coincident with formation of the vesicles associated with the nuclear membrane, which hosted nucleocapsids released from the nucleus. These data suggest that gp16 is not required for viral replication, but may be involved in membrane trafficking associated with the envelopment/de-envelopment of budded viruses when they cross over the nuclear membrane and pass through cytoplasm. PMID- 25113903 TI - 3,4-methylenedioxymethamphetamine (MDMA--Ecstasy) decreases neutrophil activity through the glucocorticoid pathway and impairs host resistance to Listeria monocytogenes infection in mice. AB - Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine (MDMA) that decreases immunity in animals. The mechanisms that generate such alterations are still controversial. Seven independent pharmacological approaches were performed in mice to identify the possible mechanisms underlying the decrease of neutrophil activity induced by MDMA and the possible effects of MDMA on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg kg(-1)) administration decreases NFkappaB expression in circulating neutrophils. Metyrapone or RU-486 administration prior to MDMA treatment abrogated MDMA effects on neutrophil activity and NFkappaB expression, while 6-OHDA or ICI 118,551 administration did not. As MDMA treatment increased the plasmatic levels of adrenaline and noradrenaline, propranolol pre-treatment effects were also evaluated. Propranolol suppressed both MDMA-induced increase in corticosterone serum levels and its effects on neutrophil activity. In a L. monocytogenes experimental infection context, we showed that MDMA: induced myelosuppression by decreasing granulocyte-macrophage hematopoietic progenitors (CFU-GM) in the bone marrow but increased CFU-GM in the spleen; decreased circulating leukocytes and bone marrow cellularity and increased spleen cellularity; decreased pro inflammatory cytokine (IL-12p70, TNF, IFN-gamma, IL-6) and chemokine (MCP-1) production 24 h after the infection; increased the production of pro-inflammatory cytokines and chemokines 72 h after infection and decreased IL-10 levels at all time points analyzed. It was proposed that MDMA immunosuppressive effects on neutrophil activity and host resistance to L monocytogenes rely on NFkappaB signaling, being mediated by HPA axis activity and corticosterone. PMID- 25113906 TI - The identification and characterization of nucleic acid chaperone activity of human enterovirus 71 nonstructural protein 3AB. AB - Human enterovirus 71 (EV71) belongs to the genus Enterovirus in the family Picornaviridae and has been recognized as one of the most important pathogens that cause emerging infectious disease. Despite of the importance of EV71, the nonstructural protein 3AB from this virus is little understood for its function during EV71 replication. Here we expressed EV71 3AB protein as recombinant protein in a eukaryotic expression system and uncovered that this protein possesses a nucleic acid helix-destabilizing and strand annealing acceleration activity in a dose-dependent manner, indicating that EV71 3AB is a nucleic acid chaperone protein. Moreover, we characterized the RNA chaperone activity of EV71 3AB, and revealed that divalent metal ions, such as Mg(2+) and Zn(2+), were able to inhibit the RNA helix-destabilizing activity of 3AB to different extents. Moreover, we determined that 3B plus the last 7 amino acids at the C-terminal of 3A (termed 3B+7) possess the RNA chaperone activity, and five amino acids, i.e. Lys-80, Phe-82, Phe-85, Tyr-89, and Arg-103, are critical and probably the active sites of 3AB for its RNA chaperone activity. This report reveals that EV71 3AB displays an RNA chaperone activity, adds a new member to the growing list of virus-encoded RNA chaperones, and provides novel knowledge about the virology of EV71. PMID- 25113907 TI - Infectious cDNA clones of the crinivirus Tomato chlorosis virus are competent for systemic plant infection and whitefly-transmission. AB - Tomato chlorosis virus (ToCV) (genus Crinivirus, family Closteroviridae) causes important emergent diseases in tomato and other solanaceous crops. ToCV is not transmitted mechanically and is naturally transmitted by whiteflies. The ToCV genome consists of two molecules of linear, positive-sense RNA encapsidated into long flexuous virions. We present the construction of full-length cDNA clones of the ToCV genome (RNA1 and RNA2) fused to the SP6 RNA polymerase promoter and under the control of the CaMV 35S promoter. RNA1 replicated in the absence of RNA2 in Nicotiana benthamiana and tomato protoplasts after inoculation with cDNA derived in vitro transcripts. Agroinfiltration of RNA1 and RNA2 under the 35S promoter resulted in systemic infection in N. benthamiana plants. In addition, tomato plants were infected by grafting with agroinfected N. benthamiana scions, showing the typical ToCV symptoms. The viral progeny generated in tomato was transmissible by the whitefly Bemisia tabaci. PMID- 25113909 TI - Palmitoylation of the Alphacoronavirus TGEV spike protein S is essential for incorporation into virus-like particles but dispensable for S-M interaction. AB - The spike protein S of coronaviruses contains a highly conserved cytoplasmic cysteine-rich motif adjacent to the transmembrane region. This motif is palmitoylated in the Betacoronaviruses MHV and SARS-CoV. Here, we demonstrate by metabolic labeling with [(3)H]-palmitic acid that the S protein of transmissible gastroenteritis coronavirus (TGEV), an Alphacoronavirus, is palmitoylated as well. This is relevant for TGEV replication as virus growth was compromised by the general palmitoylation inhibitor 2-bromopalmitate. Mutation of individual cysteine clusters in the cysteine-rich motif of S revealed that all cysteines must be replaced to abolish acylation and incorporation of S into virus-like particles (VLP). Conversely, the interaction of S with the M protein, essential for VLP incorporation of S, was not impaired by lack of palmitoylation. Thus, palmitoylation of the S protein of Alphacoronaviruses is dispensable for S-M interaction, but required for the generation of progeny virions. PMID- 25113908 TI - HIV-1 Vpu mediated downregulation of CD155 requires alanine residues 10, 14 and 18 of the transmembrane domain. AB - HIV-1 NL4-3 Vpu induces downregulation of cell surface CD155, a ligand for the DNAM-1 activating receptor of NK and CD8(+) T cells, to evade NK cell mediated immune response. Here we show that the conserved alanine residues at positions 10, 14 and 18 in the TM domain of Vpu are required for the efficient downregulation of cell surface CD155. In contrast, the CK-2 phosphorylation sites and the second alpha-helix in the cytoplasmic Vpu domain have no influence on the surface expression of CD155. Thus, compared to Vpu's effect on CD4, NTB-A and tetherin, the Vpu mediated downregulation of CD155 is an independent Vpu function. We finally show that in contrast to other lentiviral strains, only Vpu and Nef from HIV-1 M NL4-3 potently interfere with CD155 surface expression. Thus, Vpu seems to subvert NK cell responses against HIV-1 infected T cells by modulation of receptors necessary for NK cell activation. PMID- 25113910 TI - 8-Hydroxy-2'-deoxyguanosine as a biomarker of oxidative DNA damage induced by perfluorinated compounds in TK6 cells. AB - 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is the most common biomarker of oxidative DNA damage, it is formed by chemical carcinogens and can be measured in any species. Perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) are suspected genotoxic carcinogens through induction of reactive oxygen species that are responsible for oxidative DNA damage. This study was conducted to investigate the in vitro genotoxicity of PFOA and PFNA in human lymphoblastoid (TK6) cell line. TK6 cells were exposed to PFOA at 0, 125, 250, and 500 ppm and PFNA at 125 and 250 ppm for 2 h. Single cell gel electrophoresis (comet assay) was used to measure DNA damage; at least 50 cells per sample were analyzed using comet Assay Software Project (CASP). 8-OHdG was measured in DNA of exposed cells using high performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS. Results showed that both PFOA and PFNA induced DNA damage indicated by increased tail length (DNA migration). The level of 8-OHdG was increased in a dose-dependent manner in both PFOA and PFNA exposure. We concluded that PFOA and PFNA induced DNA damage and the biomarker of oxidative DNA damage (8-OHdG) could be measured by HPLC-MS/MS. In addition, PFNA produced high level of 8-OHdG at concentrations lower than PFOA, this may indicate that PFNA is more potent genotoxicant for TK6 cells than PFOA. PMID- 25113911 TI - Simultaneous T1 and T2 quantification of the myocardium using cardiac balanced SSFP inversion recovery with interleaved sampling acquisition (CABIRIA). AB - PURPOSE: To develop a novel sequence for simultaneous quantification of T1 and T2 relaxation times in the myocardium based on the transient phase of the balanced steady-state free precession. METHODS: A new prototype sequence, named "cardiac balanced-SSFP inversion recovery with interleaved sampling acquisition" (CABIRIA) was developed based on a single-shot bSSFP readout following an inversion pulse. With this method, T1 and T2 values can be calculated from the analysis of signal evolution. The scan duration for a single slice in vivo was 8 heartbeats, thus feasible in a breath-hold. The sequence was validated both in vitro by comparing it to conventional inversion recovery and multi-echo spin-echo methods and in 5 healthy volunteers by comparing it to the Modified Look-Locker Inversion Recovery (MOLLI) sequence and to a T2 quantification sequence based on multi-T2 -prepared bSSFP. RESULTS: The method showed good agreement with conventional methods for both T1 and T2 measurements (concordance correlation coefficient >= 0.99) in vitro. In healthy volunteers the measured T1 values were 1227 +/- 68 ms and T2 values 37.9 +/- 2.4 ms, with similar inter- and intrasubject variability with respect to existing methods. CONCLUSION: The proposed CABIRIA method enables simultaneous quantification of myocardial T1 and T2 values with good accuracy and precision. PMID- 25113913 TI - A simple and precise diagnostic method for spinal muscular atrophy using a quantitative SNP analysis system. AB - A simple and precise diagnostic method for spinal muscular atrophy (SMA) using high-resolution CE-based single-strand conformation polymorphism (CE-SSCP) was developed in this study. SMA is a common genetic disorder caused by an abnormality in the relative copy numbers of SMN1 and its centromeric copy SMN2, which differ only in two nucleotides, namely at exons 7 and 8. Therefore, the precise discrimination of the differences in sequence as well as their relative quantities is crucial for the diagnosis of SMA. Multiplex ligation-dependent probe amplification and sequence-sensitive DNA separation using hydroxyethyl cellulose and hydroxypropyl cellulose blended polymer matrix are currently the available methods used in the diagnosis of SMA. However, these methods are limited by their extended hybridization step and low resolution. In this study, the simultaneous discrimination of SMN exons 7 and 8 was successfully demonstrated using high-resolution CE-SSCP. Unlike the previously reported alternative method, single base differing amplicons were baseline-separated because of its extraordinary resolution, thus providing accurate and precise quantification of each paralog. PMID- 25113912 TI - Cooperative signaling between homodimers of metabotropic glutamate receptors 1 and 5. AB - Metabotropic glutamate receptors (mGluRs) function as dimers. Recent work suggests that mGluR1 and mGluR5 may physically interact, but the nature and functional consequences of this relationship have not been addressed. In this study, the functional and pharmacological consequences of this interaction were investigated. Using heterologous expression of mGluR cDNA in rat sympathetic neurons from the superior cervical ganglion and inhibition of the native calcium currents as an assay for receptor activation, a functional interdependence between mGluR1 and mGluR5 was demonstrated. In neurons coexpressing these receptors, combining a selective mGluR1 competitive antagonist with either an mGluR1- or mGluR5-selective negative allosteric modulator (NAM) BAY36-7620 [(3aS,6aS)-hexahydro-5-methylene-6a-(2-naphthalenylmethyl)-1H-cyclopenta[c]furan 1-one] or MPEP [2-methyl-6-(phenylethynyl)pyridine hydrochloride], respectively, strongly occluded signaling by both receptors to an approximately equal degree. By contrast, in cells coexpressing mGluR1 and mGluR2, combining the same mGluR1 competitive inhibitor with an mGluR1 or mGluR2 NAM yielded partial and full inhibition of the response, respectively, as expected for independently acting receptors. In neurons expressing mGluR1 and mGluR5, the selective NAMs each strongly inhibited the response to glutamate, suggesting that these receptors do not interact as heterodimers, which would not be inhibited by selective NAMs. Finally, evidence for a similar mGluR1/mGluR5 functional dependence is shown in medium spiny striatal neurons. Together, these data demonstrate cooperative signaling between mGluR1 and mGluR5 in a manner inconsistent with heterodimerization, and thus suggest an interaction between homodimers. PMID- 25113914 TI - ODE/PDE analysis of corneal curvature. AB - The starting point for this paper is a nonlinear, two-point boundary value ordinary differential equation (BVODE) that defines corneal curvature according to a static force balance. A numerical solution to the BVODE is computed by first converting the BVODE to a parabolic partial differential equation (PDE) by adding an initial value (t, pseudo-time) derivative to the BVODE. A numerical solution to the PDE is then computed by the method of lines (MOL) with the calculation proceeding to a sufficiently large value of t such that the derivative in t reduces to essentially zero. The PDE solution at this point is also the solution for the BVODE. This procedure is implemented in R (an open source scientific programming system) and the programming is discussed in some detail. A series approximation to the solution is derived from which an estimate for the rate of convergence is obtained. This is compared to a fitted exponential model. Also, two linear approximations are derived, one of which leads to a closed form solution. Both provide solutions very close to that obtained from the full nonlinear model. An estimate for the cornea radius of curvature is also derived. The paper concludes with a discussion of the features of the solution to the ODE/PDE system. PMID- 25113916 TI - Infants' ability to respond to depth from the retinal size of human faces: comparing monocular and binocular preferential-looking. AB - To examine sensitivity to pictorial depth cues in young infants (4 and 5 months of-age), we compared monocular and binocular preferential looking to a display on which two faces were equidistantly presented and one was larger than the other, depicting depth from the size of human faces. Because human faces vary little in size, the correlation between retinal size and distance can provide depth information. As a result, adults perceive a larger face as closer than a smaller one. Although binocular information for depth provided information that the faces in our display were equidistant, under monocular viewing, no such information was provided. Rather, the size of the faces indicated that one was closer than the other. Infants are known to look longer at apparently closer objects. Therefore, we hypothesized that infants would look longer at a larger face in the monocular than in the binocular condition if they perceived depth from the size of human faces. Because the displays were identical in the two conditions, any difference in looking-behavior between monocular and binocular viewing indicated sensitivity to depth information. Results showed that 5-month-old infants preferred the larger, apparently closer, face in the monocular condition compared to the binocular condition when static displays were presented. In addition, when presented with a dynamic display, 4-month-old infants showed a stronger 'closer' preference in the monocular condition compared to the binocular condition. This was not the case when the faces were inverted. These results suggest that even 4 month-old infants respond to depth information from a depth cue that may require learning, the size of faces. PMID- 25113915 TI - Chronic Delta9-tetrahydrocannabinol administration may not attenuate simian immunodeficiency virus disease progression in female rhesus macaques. AB - Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9 tetrahydrocannabinol; Delta(9)-THC dronabinol). Previously, we demonstrated that chronic Delta(9)-THC administration decreases early mortality in male simian immunodeficiency virus (SIV)-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either Delta(9)-THC (0.18-0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic Delta(9)-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4(+)/CD8(+) ratio, were not altered by Delta(9)-THC compared to control females; however, females that received chronic Delta(9)-THC did not gain as much weight as control animals. In addition, Delta(9)-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4(+) and CD8(+) T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic Delta(9)-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic Delta(9)-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of Delta(9)-THC and other cannabinoids on the HIV disease course and their implications for virus transmission. PMID- 25113918 TI - Thrombotic thrombocytopenic purpura presenting with pathologic fracture: a case report. AB - Thrombotic thrombocytopenic purpura is an acute syndrome with abnormalities in multiple organ systems, which becomes manifest with microangiopathic hemolytic anemia and thrombocytopenia. The hereditary or acquired deficiency of ADAMTS-13 activity leads to an excess of high molecular weight von Willebrand factor multimers in plasma, leading to platelet aggregation and diffuse intravascular thrombus formation, resulting in thrombotic thrombocytopenic purpura. Thrombotic lesions occurring in TTP leads to ischemia and convulsion. Depending on the properties of the bony tissue, fractures are divided into three groups as traumatic, pathological, and stress fractures. A pathologic fracture is a broken bone caused by disease leading to weakness of the bone. This process is most commonly due to osteoporosis, but may also be due to other pathologies such as cancer, infections, inherited bone disorders, or a bone cyst. We herein report a case with a pathologic fracture due to convulsion secondary to thrombotic thrombocytopenic pupura. Thrombotic lesions occurring in TTP may lead to ischemia and convulsion, as in our patient and pathological fractures presented in our case report may occur as a result of severe muscle contractions associated with convulsive activity. Thrombotic thrombocytopenic pupura is a disease that involves many organ systems and thus may have a very wide spectrum of clinical presentations. PMID- 25113917 TI - Maternal prenatal stress and infant regulatory capacity in Mexican Americans. AB - The early postpartum period lays important groundwork for later self-regulation as infants' dispositional traits interact with caregivers' co-regulatory behaviors to produce the earliest forms of self-regulation. Although emerging literature suggests that fetal exposure to maternal stress may be integral in determining child self-regulatory capacity, the complex pathways that characterize these early developmental processes remain unclear. The current study considers these complex, transactional processes in a low income, Mexican American sample. Data were collected from 295 Mexican American infants and their mothers during prenatal, 6- and 12-week postpartum home interviews. Mother reports of stress were obtained prenatally, and mother reports of infant temperament were obtained at 6 weeks. Observer ratings of maternal sensitivity and infant regulatory behaviors were obtained at the 6- and 12-week time points. Study results indicate that prenatal stress predicts higher levels of infant negativity and surgency, both of which directly or interactively predict later engagement in regulatory behaviors. Unexpectedly, prenatal stress also predicted more engagement in orienting, but not self-comforting behaviors. Advancing understandings about the nature of these developmental pathways may have significant implications for targets of early intervention in this high risk population. PMID- 25113919 TI - Response to Dr. Rice M and colleagues on their letter to editor regarding "validation of a non-invasive pulse CO-oximetry based hemoglobin estimation in normal blood donors," Transfusion and Apheresis Science 2013 Nov 4. Accurate enough for the spectrum tested. PMID- 25113920 TI - [Transferable skills of healthcare professionals in providing homecare in chronically ill patients]. AB - AIM: To determine the relevance level of non-technical skills of those professionals dedicated to the healthcare of patients with chronic diseases, from an analysis of home care professionals. DESIGN: Quantitative and qualitative research conducted in 2 phases: 1.st from November 2010 to March 2011 and 2.nd from December 2012 to August 2013. SETTING: Health Region of Barcelona city. PARTICIPANTS: During the 1.st phase, 30 professionals from homecare teams (3 from Primary Care and 3 from Hospitals). In 2.nd phase, 218 professionals from 50 Primary Healthcare Centres and 7 home care programmes. METHOD: Purposive sampling in was used in the1st phase, and randomized sampling in the 2.nd phase. Likert scales and focus group were used. RESULTS: A total of 19 skill categories were identified in the 1.st phase. In the 2.nd phase 3 metacategories were established: comprehensive patient-centered care, interprofessional organization, and inter-health care fields and interpersonal skills. CONCLUSIONS: It is necessary to improve and secure the professionals relationships between levels of healthcare, continuity of healthcare, biopsychosocial model and holistic attention to patients and relatives, looking at emotions, expectations, feelings, beliefs and values. It is essential to design and implement continuing training in transferable skills in every healthcare centre, through active methodologies. PMID- 25113921 TI - [Inappropriate prescribing in polymedicated patients over 64 years-old in primary care]. AB - OBJECTIVE: To describe inappropriate prescribing (IP) in the polymedicated population over 64 years-old in primary care using the STOPP/START criteria. DESIGN: The study design was descriptive, cross-sectional and multicenter. LOCATION: Four urban primary care centers in Barcelona. Participants Patients over 64 years-old with more than 5 prescribed drugs for at least 6 months (n=467). Main measurements Major health problems, chronically prescribed drugs, and percentage of IP using the STOPP/START criteria were studied. Percentage of IP considered as the percentage of patients with at least one STOPP or START non compliance criterion was calculated with a 95%CI. Chi-square was used for statistical analysis. RESULTS: The mean age was 77.3 (+/- 7.0 SD) with a mean of 8.9 (+/- 2.8 SD) prescribed drugs. IP was higher the greater the number of drugs prescribed (p<0,01). 326 patients (76.4% [95%CI: 72.2 to 80.6]) had at least one IP, according to STOPP/START criteria. STOPP IP affected 51.4% of the patients and START IP 53.6%. The most frequent causes of IP were antiplatelet agents, for both over-prescribing (10.2%) and omission (17.9%). Prolonged use of benzodiazepines (6.6%) and duplications (6.4%) followed in prevalence. CONCLUSIONS: IP in polymedicated patients in primary care was very high. IP was similar for drugs that should be withdrawn or started. The most common causes of IP were antiplatelet agents, benzodiazepines and drug duplication. PMID- 25113922 TI - [The adaptation and validation to Spanish of the questionnaire Aid to Capacity Evaluation (ACE), for the assessment of the ability of patients in medical decision-making]. AB - OBJECTIVE: To adapt and validate the Spanish version of the Aid to Capacity Evaluation scale, designed to assess the capacity of the adult in medical decision-making, both in diagnosis and treatment processes. DESIGN: Observational study of prospective validation. SETTING: Primary and hospital care of the basic health area of Jaen. PARTICIPANTS: One hundred twenty-nine patients. MAIN MEASUREMENTS: Questionnaire which included sociodemographic variables, concerning the decision (scope, type of decision, the need for written informed consent), assessment of the capacity to the Aid to Capacity Evaluation scale and other related comorbidity (hearing loss, alcoholism, cognitive level variables with the Mini-Mental State Examination and depression by Goldberg or Yesavage test). RESULTS: The tool is considered viable. The conclusions of the expert panel were favorable. The result of the criteria' validity, comparing the results with the assessment of the experts (forensic and psychiatrist) was very satisfying (P<.001). The intra-observer reliability was low (kappa=0,135). Interobserver reliability remained high (kappa=0.74). The internal consistency was awarded an alpha of Cronbach's 0,645 for the reduced model of 6 items. CONCLUSIONS: The Aid to Capacity Evaluation scale was adapted to Spanish, demonstrating adequate internal consistency and construct validity. Its use in clinical practice could contribute to the identification of patients unable to make a particular medical decision and/or to give an informed consent. PMID- 25113923 TI - Can the therapeutic relationship predict 18 month outcomes for individuals with psychosis? AB - Therapeutic relationships (TRs) are considered a key component of good psychiatric care, yet its association with outcomes for individuals with psychosis remains unclear. Five hundred and sixty-nine service users with psychotic disorders and care coordinators in community settings rated their therapeutic relationship; outcomes were assessed 18 months later. In multivariate analyses, a small but significant association was found between service user ratings and instances of psychiatric hospital admissions, self harm and suicide attempts over an 18 month period. Care coordinator ratings were associated with instances of psychiatric hospital admissions and harm to others over the 18 months and level of functioning at 18 months. The differential findings and small effect size suggests that the therapeutic relationship needs further definition for this patient group in this setting. Nevertheless, clinicians should prioritise interactions that strengthen therapeutic relationships. PMID- 25113924 TI - Prevalence of schizophrenia disability and associated mortality among Chinese men and women. AB - Schizophrenia is a major cause of psychiatric disability in China. In the present study, we estimated total and age-specific prevalence of both schizophrenia disability and associated mortality among Chinese women and men. We further examined whether sex differences in prevalence were attributable to mortality differences between men and women. Data from the Second China National Sample Survey on Disability (2006) and the 2007-2010 follow-up studies were utilized. Possibly psychiatrically disabled individuals were administered the World Health Organization Disability Assessment Schedule, Version II and the ICD-10 Symptom Checklist for Mental Disorders by trained clinical psychiatrists. In total, 0.37% of men and 0.44% of women were living with schizophrenia disability in China. We did not find statistically significant differences in the 4-year cumulative mortality between men and women. Overall standardized mortality ratios for the age groups of 18-29, 30-39, 40-49, 50-59, 60-69, and 70+ years were 120.89, 29.56, 15.06, 9.16, 10.57, and 4.95, respectively. In conclusion, mortality differences between men and women were unlikely to be a major contributor to sex differences in prevalence. Premature death among younger individuals experiencing schizophrenia disability warrants urgent attention. PMID- 25113925 TI - Sweet taste sensitivity is influenced by 5-HTTLPR genotype and affected in seasonal affective disorder. PMID- 25113926 TI - Biogenetic explanations and emotional reactions to people with schizophrenia and major depressive disorder. AB - Using population-based data, the relationship between biogenetic causal beliefs and emotional reactions to persons with schizophrenia or depression was examined. Biogenetic attributions elicited either negative emotions alone or pro-social and negative emotions at the same time. Biogenetic attributions seem not helpful for improving emotional reactions to people with mental disorders. PMID- 25113927 TI - Phosphathiahelicenes: synthesis and uses in enantioselective gold catalysis. AB - Enantiomerically pure thiahelicenes displaying a terminal phosphole unit and a stereogenic phosphorus center have been prepared by oxidative photocyclization of a diaryl-olefin precursor. Starting from one of these phosphathiahelicene oxides, the corresponding trivalent phosphine-Au(I) complex is obtained with complete diastereoselectivity. It affords a new, excellent precatalyst for the enantioselective cycloisomerization of N-tethered enynes (up to 96 % ee). PMID- 25113928 TI - High accuracy NMR chemical shift corrected for bulk magnetization as a tool for structural elucidation of dilutable microemulsions. Part 1 - Proof of concept. AB - In microemulsions, changes in droplet size and shape and possible transformations occur under various conditions. They are difficult to characterize by most analytical tools because of their nano-sized structure and dynamic nature. Several methods are usually combined to obtain reliable information, guiding the scientist in understanding their physical behavior. We felt that there is a need for a technique that complements those in use today in order to provide more information on the microemulsion behavior, mainly as a function of dilution with water. The improvement of NMR chemical shift measurements independent of bulk magnetization effects makes it possible to study the very weak intermolecular chemical shift effects. In the present study, we used NMR high resolution magic angle spinning to measure the chemical shift very accurately, free of bulk magnetization effects. The chemical shift of microemulsion components is measured as a function of the water content in order to validate the method in an interesting and promising, U-type dilutable microemulsion, which had been previously studied by a variety of techniques. Phase transition points of the microemulsion (O/W, bicontinuous, W/O) and changes in droplet shape were successfully detected using high-accuracy chemical shift measurements. We analyzed the results and found them to be compatible with the previous studies, paving the way for high-accuracy chemical shifts to be used for the study of other microemulsion systems. We detected two transition points along the water dilution line of the concentrate (reverse micelles) corresponding to the transition from swollen W/O nano-droplets to bicontinuous to the O/W droplets along with the changes in the droplets' sizes and shapes. The method seems to be in excellent agreement with other previously studied techniques and shows the advantage of this easy and valid technique. PMID- 25113929 TI - Radium isotopes ((226)Ra and (228)Ra) in Na-Cl type groundwaters from Tohoku District (Aomori, Akita and Yamagata Prefectures) in Japan. AB - A total of 28 Na-Cl type groundwater samples were collected from Aomori, Akita and Yamagata Prefectures, in the Tohoku District of Japan, and their radium isotope ((226)Ra and (228)Ra) concentrations were measured along with their chemical components and stable isotope ratios (delta(2)H and delta(18)Os). The (226)Ra concentrations in groundwater samples varied widely, ranging from 8.8 to 1587 mBq kg(-1). These concentrations showed an increasing tendency with the increase of the total dissolved solid (TDS) contents. The (228)Ra/(226)Ra activity ratios were in the range from 0.3 to 4.2, with most data being around 0.5-2. These ratios were within those of (232)Th/(238)U found in granitic and related rocks and so on in Japan, indicating that Ra isotopes mainly ejected into the groundwater by the alpha-recoil process. The relationship between (226)Ra and other parameters suggested that Ra isotopes in groundwater samples in this study were mainly constrained by adsorption-desorption reactions depending on salinity with wide variation. Clear correlation between (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS observed in sulfate-free groundwater samples indicated that Ra isotopes of them were constrained by adsorption-desorption reactions depending on salinity under reducing condition. In contrast, relationship of (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS in sulfate-containing groundwater samples varied widely, and then, removal or enhanced mobility of Ra isotopes of them were observed. PMID- 25113931 TI - In search of next generation antimalarials. AB - Compounds 7-10 displayed potency without any apparent toxicity, in animal models of both relapsing and non-relapsing forms of malaria offering hope of a single molecule that can cure both relapsing and non relapsing forms of malaria. PMID- 25113930 TI - Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a [1,2,4]triazolo[4,3-b]pyridazine scaffold. AB - Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's disease (PD). The most common mutant, G2019S, increases kinase activity, thus LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein disclose the structure, potential ligand-protein binding interactions, and pharmacological profiling of potent and highly selective kinase inhibitors based on a triazolopyridazine chemical scaffold. PMID- 25113932 TI - Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally bioavailable and selective P2Y(12) antagonists for inhibition of platelet aggregation. AB - 2-Phenyl-pyrimidine-4-carboxamide analogs were identified as P2Y12 antagonists. Optimization of the carbon-linked or nitrogen-linked substituent at the 6 position of the pyrimidine ring provided compounds with excellent ex vivo potency in the platelet aggregation assay in human plasma. Compound 23u met the objectives for activity, selectivity and ADMET properties. PMID- 25113934 TI - Discovery of pyrrolo-benzo-1,4-diazines as potent Na(v)1.7 sodium channel blockers. AB - A series of pyrrolo-benzo-1,4-diazine analogs have been synthesized and displayed potent Nav1.7 inhibitory activity and moderate selectivity over Nav1.5. The syntheses, structure-activity relationships, and selected pharmacokinetic data of these analogs are described. Compound 41 displayed anti-nociceptive efficacy in the rat CFA pain model at 100 mpk oral dosing. PMID- 25113933 TI - Oleanolic acid analogs as NO, TNF-alpha and IL-1beta inhibitors: synthesis, biological evaluation and docking studies. AB - A series of oleanolic acid analogs, characterized by structural modifications at position C-3 and C-28 of oleanane skeleton were synthesized and assessed for antiinflammatory potential towards lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophages. Results revealed that all the synthesized analogs of oleanolic acid inhibit NO production with an IC50 of 2.66-41.7 MUM as compared to the specific nitric oxide synthase (NOS) inhibitor, L-NAME (IC50=69.21 and 73.18 MUM on RAW 264.7 and J774A.1 cells, respectively) without affecting the cell viability when tested at their half maximal concentration. The most potent NO inhibitors (2, 8, 9 and 10) at a concentration of 20 MUg/mL also demonstrated mild inhibition (27.9-51.9%) of LPS-induced tumor necrosis factor alpha (TNF alpha) and weak inhibition (11.1-37.5%) towards interleukin 1-beta (IL-1beta) production in both the cells. The present study paves a direction that analogs of oleanolic acid can be employed as a lead in the development of potent NO inhibitors. Molecular docking studies also showed that 10 (with top Goldscore docking pose 19.05) showed similar interaction as that of co-crystallized inhibitor and, thereby, helps to design the potent inhibitors of TNF-alpha. PMID- 25113935 TI - Cellular differentiation assessments by measuring the degree of cellular internalization and membrane adsorption using designed peptides. AB - We demonstrate examples of cellular differentiation assessments, including cellular neurite outgrowth and fat cell maturation, by measuring the degree of membrane adsorption or cellular internalization using designed peptides. Because changes in the cellular membrane and cytosol during differentiation were shown to influence membrane adsorption and cellular internalization, we could successfully evaluate the extent of differentiation simply like stain indicators. PMID- 25113936 TI - Online dietary intake estimation: reproducibility and validity of the Food4Me food frequency questionnaire against a 4-day weighed food record. AB - BACKGROUND: Advances in nutritional assessment are continuing to embrace developments in computer technology. The online Food4Me food frequency questionnaire (FFQ) was created as an electronic system for the collection of nutrient intake data. To ensure its accuracy in assessing both nutrient and food group intake, further validation against data obtained using a reliable, but independent, instrument and assessment of its reproducibility are required. OBJECTIVE: The aim was to assess the reproducibility and validity of the Food4Me FFQ against a 4-day weighed food record (WFR). METHODS: Reproducibility of the Food4Me FFQ was assessed using test-retest methodology by asking participants to complete the FFQ on 2 occasions 4 weeks apart. To assess the validity of the Food4Me FFQ against the 4-day WFR, half the participants were also asked to complete a 4-day WFR 1 week after the first administration of the Food4Me FFQ. Level of agreement between nutrient and food group intakes estimated by the repeated Food4Me FFQ and the Food4Me FFQ and 4-day WFR were evaluated using Bland Altman methodology and classification into quartiles of daily intake. Crude unadjusted correlation coefficients were also calculated for nutrient and food group intakes. RESULTS: In total, 100 people participated in the assessment of reproducibility (mean age 32, SD 12 years), and 49 of these (mean age 27, SD 8 years) also took part in the assessment of validity. Crude unadjusted correlations for repeated Food4Me FFQ ranged from .65 (vitamin D) to .90 (alcohol). The mean cross-classification into "exact agreement plus adjacent" was 92% for both nutrient and food group intakes, and Bland-Altman plots showed good agreement for energy-adjusted macronutrient intakes. Agreement between the Food4Me FFQ and 4-day WFR varied, with crude unadjusted correlations ranging from .23 (vitamin D) to .65 (protein, % total energy) for nutrient intakes and .11 (soups, sauces and miscellaneous foods) to .73 (yogurts) for food group intake. The mean cross-classification into "exact agreement plus adjacent" was 80% and 78% for nutrient and food group intake, respectively. There were no significant differences between energy intakes estimated using the Food4Me FFQ and 4-day WFR, and Bland-Altman plots showed good agreement for both energy and energy controlled nutrient intakes. CONCLUSIONS: The results demonstrate that the online Food4Me FFQ is reproducible for assessing nutrient and food group intake and has moderate agreement with the 4-day WFR for assessing energy and energy-adjusted nutrient intakes. The Food4Me FFQ is a suitable online tool for assessing dietary intake in healthy adults. PMID- 25113939 TI - Estimated life expectancy and risk of death from cancer by quartiles in the older Japanese population: 2010 vital statistics. AB - Data on life expectancies and risk of death from cancer are essential information to have when making informed decisions about cancer screening and treatment options, but has never been presented in a way that is readily available to use for physicians in Japan. We provided estimates of life expectancies and predicted risk of death from seven most common types of cancer (lung, gastric, liver, colon, prostate, breast, and cervical) by quartiles for the older Japanese population above 50 years old, using 2010 life tables and cancer mortality statistics data. We found that there was a large difference in life expectancy between older persons in the upper and lower quartiles. Risk of death from breast cancer was low. By using this data, physicians can more accurately obtain life expectancy estimates by assessing which quartile the patient is most likely to fall under, and help patients make better informed decisions. PMID- 25113940 TI - Epidemiology of childhood leukemia in the presence and absence of Down syndrome. AB - Down syndrome (DS) is a common congenital anomaly, and children with DS have a substantially higher risk of leukemia. Although understanding of genetic and epigenetic changes of childhood leukemia has improved, the causes of childhood leukemia and the potential role of environmental exposures in leukemogenesis remain largely unknown. Although many epidemiologic studies have examined a variety of environmental exposures, ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia. Among suspected risk factors, infections, exposure to pesticides, and extremely low frequency magnetic fields are notable. While there are well-defined differences between leukemia in children with and without DS, studies of risk factors for leukemia among DS children are generally consistent with trends seen among non-DS (NDS) children. We provide background on DS epidemiology and review the similarities and differences in biological and epidemiologic features of leukemia in children with and without DS. We propose that both acute lymphoblastic and acute myeloblastic leukemia among DS children can serve as an informative model for development of childhood leukemia. Further, the high rates of leukemia among DS children make it possible to study this disease using a cohort approach, a powerful method that is unfeasible in the general population due to the rarity of childhood leukemia. PMID- 25113938 TI - Statin use and risk of hepatocellular carcinoma in a U.S. population. AB - PURPOSE: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are medications widely prescribed to reduce cholesterol levels. Observational studies in high-risk populations, mostly in Asia, have suggested that statins are associated with a reduced risk of hepatocellular carcinoma (HCC). The current study sought to evaluate the association of statin use and HCC in a U.S.-based, low-risk, general population. METHODS: A nested case-control study was conducted among members of the Health Alliance Plan HMO of the Henry Ford Health System enrolled between 1999 and 2010. Electronic pharmacy records of statin use were compared among tumor registry-confirmed cases of HCC (n=94) and controls (n=468) matched on age, sex, diagnosis date, and length of HMO enrolment. RESULTS: In multivariate analyses, ever-use of statins was significantly inversely associated with development of HCC (Odds ratio (OR): 0.32, 95%CI: 0.15-0.67). No clear dose response relationship was evident as statin use for <2 years (OR=0.32, 95%CI=0.13 0.83) and >2 years (OR=0.31, 95CI%=0.12-9.81) resulted in very similar ORs. CONCLUSIONS: The use of statins among populations in low-risk HCC areas may be associated with decreased risk of HCC. PMID- 25113942 TI - A practical tool to evaluate dose distributions using radiochromic film in radiation oncology. AB - PURPOSE: Triple channel algorithm and specific procedures make more reliable radiochromic dosimetry for treatment planning verification and quality assurance in radiation therapy. A tool to obtain radiochromic dose distributions and compare them with the ones resulting from a treatment planning system was developed and applied. METHODS: The tool was developed as Microsoft Excel macro; it builds dose calibration curves against net optical density of Gafchromic EBT3 film, produces axial, coronal and sagittal dose maps and allows to evaluate them against dose distributions calculated by the Varian treatment planning system Eclipse using gamma index and gamma angle. RESULTS: The net optical density standard errors of estimate of calibration curves at 6 MV Varian DBX600 linac energy were 0.2%, 0.4% and 0.2% for the red, green and blue channels. Tests of these curves by means of three independent eight dose points measurement series, at 15 MV and 6 MV Varian 2100C linac and at 6 MV DBX600 linac energies, showed less than 2% of dose errors for the red channel and less than 3% for the green channel in the range 100-450 cGy. The comparisons between dose distributions from Gafchromic EBT3 triple channel algorithm and the ones from Eclipse analytic anisotropic algorithm (AAA) showed values of gamma index 95th percentile between 0.6 and 1.0. CONCLUSION: The obtained results encourage the application of this tool in radiation therapy quality assurance. PMID- 25113941 TI - Cell-friendly inverse opal-like hydrogels for a spatially separated co-culture system. AB - Three-dimensional macroporous scaffolds have extensively been studied for cell based tissue engineering but their use is mostly limited to mechanical support for cell adhesion and growth on the surface of macropores. Here, a templated fabrication method is described to prepare cell-friendly inverse opal-like hydrogels (IOHs) allowing both cell encapsulation within the hydrogel matrix and cell seeding on the surface of macropores. Ionically crosslinked alginate microbeads and photocrosslinkable biocompatible polymers are used as a sacrificial template and as a matrix, respectively. The alginate microbeads are easily removed by a chelating agent, with minimal toxicity for the encapsulated cells during template removal. The outer surface of macropores in IOHs can also provide a space for cell adherence. The cells encapsulated or attached in IOHs are able to remain viable and to proliferate over time. The elastic modulus and cell-adhesion properties of IOHs can be easily controlled and tuned. Finally, it is demonstrated that IOH can be used to co-culture two distinct cell populations in different spatial positions. This cell-friendly IOH system provides a 3D scaffold for organizing different cell types in a controllable microenvironment to investigate biological processes such as stem cell niches or tumor microenvironments. PMID- 25113944 TI - Systemic progesterone therapy--oral, vaginal, injections and even transdermal? AB - Several medicinal products containing progesterone are in widespread use orally for protection of the endometrium during concurrent oestrogen treatment, and injections or vaginally for support of luteal function during assisted reproduction. These indications have been established in extensive clinical testing programmes. In addition, the results of recent studies and meta-analyses suggest that vaginal progesterone is an effective method for preventing premature births in singleton pregnancies in women with a shortened cervix. In US, 17alpha hydroxyprogesterone caproate is licensed to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. There is insufficient evidence from scientific studies to substantiate the transdermal application of progesterone. In particular, these preparations should not be used to oppose the effects of oestrogen on the endometrium, because even with low doses of estradiol a reliable progestogenic effect to protect the endometrium has not been proved. On the other hand, the application of transdermal progesterone preparations alone is not known to pose any risks to health. PMID- 25113943 TI - Static and rotational intensity modulated techniques for head-neck cancer radiotherapy: a planning comparison. AB - PURPOSE: To compare helical Tomotherapy (HT), two volumetric-modulated arc techniques and conventional fixed-field intensity modulated techniques (S-IMRT) for head-neck (HN) cancers. METHODS AND MATERIALS: Eighteen HN patients were considered. Four treatment plans were generated for each patient: HT, S-IMRT optimised with Eclipse treatment planning system and two volumetric techniques using Elekta-Oncentra approach (VMAT) and Varian-RapidArc (RA), using two full arcs. All techniques were optimised to simultaneously deliver 66Gy to PTV1 (GTV and enlarged nodes) and 54Gy to PTV2 (subclinical and electively treated nodes). Comparisons were assessed on several dosimetric parameters and, secondarily, on planned MUs and delivery time. RESULTS: Concerning PTV coverage, significantly better results were found for HT and RA. HT significantly improved the target coverage both compared to S-IMRT and VMAT. No significant differences were found between S-IMRT and volumetric techniques in terms of dose homogeneity. For OARs, all the techniques were able to satisfy all hard constraints; significantly better results were found for HT, especially in the intermediate dose range (15 30 Gy). S-IMRT reached a significantly better OARs sparing with respect to VMAT and RA. No significant differences were found for body mean dose, excepting higher values of V5-V10 for HT. A reduction of planned MUs and delivery treatment time was found with volumetric techniques. CONCLUSIONS: The objectives of satisfying target coverage and sparing of critical structures were reached with all techniques. S-IMRT techniques were found more advantageous compared to RA and VMAT for OARs sparing. HT reached the best overall treatment plan quality. PMID- 25113945 TI - Recently targeted kinases and their inhibitors-the path to clinical trials. AB - Protein kinases have emerged as one of the most important drug target families for the treatment of cancer. To date, 28 inhibitors with reported activity versus one or multiple kinases have been approved for clinical use. However, the majority of new clinical trials are focused on new subindications using already approved kinase inhibitors or target well validated kinase targets with novel inhibitors. In contrast, relatively few clinical trials have been initiated using specific inhibitors that inhibit novel kinase targets, despite significant validation efforts in the public domain. Analysis of the target validation history of first in class kinase inhibitors revealed a long delay between initial disease association and development of inhibitors. As part of this analysis, we have investigated which first in class inhibitor that entered phase I clinical trials over the last five years and also considered which research approaches that were used to validate them. PMID- 25113946 TI - Metabolic modeling of spatial heterogeneity of biofilms in microbial fuel cells reveals substrate limitations in electrical current generation. AB - Microbial fuel cells (MFCs) have been proposed as an alternative energy resource for the conversion of organic compounds to electricity. In an MFC, microorganisms such as Geobacter sulfurreducens form an anode-associated biofilm that can completely oxidize organic matter (electron donor) to carbon dioxide with direct electron transfer to the anode (electron acceptor). Mathematical models are useful in analyzing biofilm processes; however, existing models rely on Nernst Monod type expressions, and evaluate extracellular processes separated from the intracellular metabolism of the microorganism. Thus, models that combine both extracellular and intracellular components, while addressing spatial heterogeneity, are essential for improved representation of biofilm processes. The goal of this work is to develop a model that integrates genome-scale metabolic models with the model of biofilm environment. This integrated model shows the variations of electrical current production and biofilm thickness under the presence/absence of NH4 in the bulk solution, and under varying maintenance energy demands. Further, sensitivity analysis suggested that conductivity is not limiting electrical current generation and that increasing cell density can lead to enhanced current generation. In addition, the modeling results also highlight instances such as the transformation into respiring cells, where the mechanism of electrical current generation during biofilm development is not yet clearly understood. PMID- 25113948 TI - Microalgal and cyanobacterial cultivation: the supply of nutrients. AB - Microalgae and cyanobacteria are a promising new source of biomass that may complement agricultural crops to meet the increasing global demand for food, feed, biofuels and chemical production. Microalgae and cyanobacteria cultivation does not interfere directly with food production, but care should be taken to avoid indirect competition for nutrient (fertilizer) supply. Microalgae and cyanobacteria production requires high concentrations of essential nutrients (C,N,P,S,K,Fe, etc.). In the present paper the application of nutrients and their uptake by microalgae and cyanobacteria is reviewed. The main focus is on the three most significant nutrients, i.e. carbon, nitrogen and phosphorus; however other nutrients are also reviewed. Nutrients are generally taken up in the inorganic form, but several organic forms of them are also assimilable. Some nutrients do not display any inhibition effect on microalgal or cyanobacterial growth, while others, such as NO2 or NH3 have detrimental effects when present in high concentrations. Nutrients in the gaseous form, such as CO2 and NO face a major limitation which is related mainly to their mass transfer from the gaseous to the liquid state. Since the cultivation of microalgae and cyanobacteria consumes considerable quantities of nutrients, strategies to improve the nutrient application efficiency are needed. Additionally, a promising strategy to improve microalgal and cyanobacterial production sustainability is the utilization of waste streams by recycling of waste nutrients. However, major constraints of using waste streams are the reduction of the range of the biomass applications due to production of contaminated biomass and the possible low bio-availability of some nutrients. PMID- 25113947 TI - Hybrid ferrihydrite-MF/UF membrane filtration for the simultaneous removal of dissolved organic matter and phosphate. AB - Dissolved organic matter (DOM) and phosphorus promote microbial regrowth in water distribution networks. Ferrihydrite (Fh) has a high adsorption affinity with DOM and phosphate. Hence, a lab-scale unit of the hybrid Fh-MF/UF membrane filtration system was used to evaluate membrane fouling and the removal efficiency of DOM and phosphate. Suwannee River natural organic matter (SRNOM) was used as a surrogate for DOM in natural water. The Fh-membrane system demonstrated removal rates of dissolved organic carbon (DOC), UV254 and phosphate up to 50%, 80% and 90%, respectively, at the Fh dose of 17.5 mg/L. The effect of phosphate on the removal of DOM was different without or with the addition of Fh; namely, phosphate increased the DOM removal without Fh by interacting with the UF membrane made of regenerated cellulose (RC), but phosphate decreased the DOM removal by Fh due to the strong affinity of phosphate with Fh. Size exclusion chromatography revealed that phosphate mainly competed against smaller DOM molecules for Fh adsorption sites. Although the addition of Fh caused only a moderate flux decline with the RC membranes, the deposition of positively charged Fh on the surface of a negatively charged high-flux membrane, i.e., polyethersulfone (PES), caused a rapid decline of the permeation flux. PMID- 25113949 TI - Development of a polydimethylsiloxane-thymol/nitroprusside composite based sensor involving thymol derivatization for ammonium monitoring in water samples. AB - This report describes a polydimethylsiloxane (PDMS)-thymol/nitroprusside delivery composite sensor for direct monitoring of ammonium in environmental water samples. The sensor is based on a PDMS support that contains the Berthelot's reaction reagents. To prepare the PDMS-thymol/nitroprusside composite discs, thymol and nitroprusside have been encapsulated in the PDMS matrix, forming a reagent release support which significantly simplifies the analytical measurements, since it avoids the need to prepare derivatizing reagents and sample handling is reduced to the sampling step. When, the PDMS thymol/nitroprusside composite was introduced in water samples spontaneous release of the chromophore and catalyst was produced, and the derivatization reaction took place to form the indothymol blue. Thus, qualitative analysis of NH4(+) could be carried out by visual inspection, but also, it can be quantified by measuring the absorbance at 690 nm. These portable devices provided good sensitivity (LOD<0.4 mg L(-1)) and reproducibility (RSD <10%) for the rapid detection of ammonium. The PDMS-NH4(+) sensor has been successfully applied to determine ammonium in water samples and in the aqueous extracts of particulate matter PM10 samples. Moreover, the reliability of the method for qualitative analysis has been demonstrated. Finally, the advantages of the PDMS-NH4(+) sensor have been examined by comparing some analytical and complementary characteristics with the properties of well-established ammonium determination methods. PMID- 25113950 TI - Heart rate control with single administration of a long-acting beta-blocker at bedtime before coronary computed tomography angiography. AB - BACKGROUND: Beta-blockers are used to control the heart rate prior to coronary computed tomography (CT) angiography. However, in-hospital administration is time consuming, and it is hard to decrease the heart rate to <60 beats per minute (bpm) when the initial heart rate is increased. In this study, we examined whether the single administration of long-acting beta-blocker at bedtime before angiography is effective for achieving the target heart rate. METHODS AND RESULTS: A total of 314 consecutive patients with a resting heart rate >60bpm who underwent coronary CT angiography were retrospectively collected. Either bisoprolol or atenolol was orally administered the night before to 166 patients (beta group), and no additional medication was administered to the other 148 patients (control group). When the heart rate was >60bpm on arrival, a beta blocker or verapamil was orally administered at the discretion of the physician. Although the baseline heart rate was not significantly different between the groups, the beta-blocker treatment the night before significantly reduced the heart rate compared to control group upon arrival at the hospital and at the time of angiography. The rate of achievement of a heart rate <=60bpm on arrival at the hospital was significantly higher in the beta group, and even after the additional treatment. CONCLUSIONS: Bedtime administration of a long-acting beta blocker the night before coronary CT angiography is an effective option to achieve the target heart rate at the time of examination. PMID- 25113951 TI - Management of ostium secundum atrial septal defect in the era of percutaneous trans-catheter device closure: 7-Year experience at a single institution. AB - OBJECTIVES: This study aimed to review the single institutional experience of the repair of secundum atrial septal defect (ASD) after the initiation of percutaneous trans-catheter device closure, to confirm the current management strategy and outcomes. METHODS: From August 2005 to December 2012, a total of 1026 (659 females, age 27+/-21 years) consecutive patients underwent the repair of ASD. Including eight patients who converted to surgical repair, 317 patients (31%) underwent surgical repair and 709 (69%) underwent trans-catheter device closure. RESULTS: An embolized device into the left atrium was surgically retrieved in one patient soon after trans-catheter device closure without any postoperative complications. The other patient developed left atrium to aorta fistula due to late erosion, and required the removal of implanted device and patch closure of fistula and ASD 3 months after trans-catheter device closure. Whereas serious central nerve system complications occurred in three patients after the surgical repair including a 75-year-old patient with postoperative transient atrial fibrillation who subsequently developed aspiration pneumonia and died; there were no mortalities and no morbidities associated with cranial nerve function after trans-catheter device closure. A number of patients approached through partial sternotomy with limited skin incision have increased per year, and the length of skin incision was 5.1+/-1.2cm in pediatric patients weighing less than 15kg (n=40), 6.9+/-1.9cm in the remaining pediatric patients (n=91), and 10.0+/-2.5cm in young adult females (n=10). CONCLUSION: Percutaneous trans catheter ASD closure was safely performed under the support of a surgical team. The cosmetic outcome of surgical closure is improving after initiation of partial sternotomy via limited skin incision for the pediatric population and young adult females. Prior to the treatment, the physicians must thoroughly inform patients and families of the advantages and disadvantages of both treatment options. PMID- 25113953 TI - Genotyping of exons 1 to 20 in Duchenne muscular dystrophy by universal multiplex PCR and short-end capillary electrophoresis. AB - One rapid CE method was established to diagnose Duchenne muscular dystrophy (DMD). DMD is a severe recessive inherited disorder frequently caused by gene deletions. Among them, exons 1-20 account for nearly 30% of occurrences. In this study, the universal multiplex PCR was used to enhance the fluorescently labeling efficiency, which was performed only by one universal fluorescent primer. After PCR, a short-end injection CE (short-end CE) speeded up the genotyping of the DMD gene. This method involved no extra purification, and was completed within 9 min. The CE conditions contained a polymer solution of 1.5% hydroxylethylcellulose in 1* TBE buffer at 6 kV for separation. This method was applied to test six DMD patients and one healthy male person. The results showed good agreement with those of multiplex ligation-dependent probe amplification. This method can be applied for clinical diagnosis of DMD disease. Accurate diagnosis of the DMD gene is the best way to prevent the disease. PMID- 25113952 TI - Results of catheter ablation of atrial fibrillation in hypertrophied hearts - Comparison between primary and secondary hypertrophy. AB - BACKGROUND AND PURPOSE: Approximately 20-25% of the patients with hypertrophic cardiomyopathy (HCM) develop atrial fibrillation (AF) during the clinical course of the disease, a percentage significantly larger than that of the general population. The purpose of the present study was to report on the procedural results of patients with AF and either primary or secondary left ventricular hypertrophy (LVH). METHODS AND SUBJECTS: Twenty-two consecutive HCM patients (55% male, mean age 57+/-8 years) with symptomatic AF, having undergone AF ablation procedures between September 2009 and July 2012 were compared with respect to procedural outcome and follow-up characteristics with 22 matched controls with secondary cardiac hypertrophy (64% male, 63+/-10 years) from our prospective AF catheter ablation registry. RESULTS AND CONCLUSION: Radiofrequency catheter ablation (RFCA) was successful in restoring long-term sinus rhythm in patients with LVH due to HCM and due to secondary etiology. However, patients with HCM needed more RFCA procedures and frequently additional antiarrhythmic drug therapy in order to maintain sinus rhythm. PMID- 25113954 TI - Two distinct neural mechanisms in early visual cortex determine subsequent visual processing. AB - Neuroscience research has conventionally focused on how the brain processes sensory information, after the information has been received. Recently, increased interest focuses on how the state of the brain upon receiving inputs determines and biases their subsequent processing and interpretation. Here, we investigated such 'pre-stimulus' brain mechanisms and their relevance for objective and subjective visual processing. Using non-invasive focal brain stimulation [transcranial magnetic stimulation (TMS)] we disrupted spontaneous brain state activity within early visual cortex (EVC) before onset of visual stimulation, at two different pre-stimulus-onset-asynchronies (pSOAs). We found that TMS pulses applied to EVC at either 20 msec or 50 msec before onset of a simple orientation stimulus both prevented this stimulus from reaching visual awareness. Interestingly, only the TMS-induced visual suppression following TMS at a pSOA of ?20 msec was retinotopically specific, while TMS at a pSOA of ?50 msec was not. In a second experiment, we used more complex symbolic arrow stimuli, and found TMS-induced suppression only when disrupting EVC at a pSOA of ? ?60 msec, which, in line with Experiment 1, was not retinotopically specific. Despite this topographic unspecificity of the ?50 msec effect, the additional control measurements as well as tracking and removal of eye blinks, suggested that also this effect was not the result of an unspecific artifact, and thus neural in origin. We therefore obtained evidence of two distinct neural mechanisms taking place in EVC, both determining whether or not subsequent visual inputs are successfully processed by the human visual system. PMID- 25113955 TI - Relevance of subcortical visual pathways disruption to visual symptoms in dementia with Lewy bodies. AB - Visual hallucinations represent a core diagnostic criterion for dementia with Lewy bodies (DLB). We hypothesized that thalamic regions, which are critically involved in the modulation of visual transmission, may be differentially disrupted in DLB as compared to Alzheimer's Disease (AD) and that these deficits could relate to visual dysfunction in DLB patients. Magnetic Resonance and Diffusion Tensor Imaging (DTI) were performed with a 3 T scanner on a sample population of 15 DLB patients, 15 AD patients and 13 healthy volunteers. Regional thalamic micro-structural changes were assessed by parcelling the thalamus based on its connectivity to cortex and to amygdala and by measuring the mean diffusivity (MD) in each connectivity-defined sub-region. Micro-structural grey matter damage associated to higher MD values was found bilaterally in DLB compared to controls in the sub-regions projecting from thalamus to prefrontal and parieto-occipital cortices. Right thalamic sub-region projecting to amygdala and left thalamic sub-region projecting to motor cortex were also affected in DLB compared to controls. Higher MD values were found bilaterally in AD compared to controls in the thalamic sub-regions projecting to temporal cortex. Specific comparison between the two forms of dementia found differences: the sub-regions which project from thalamus to parieto-occipital cortex and to amygdala showed higher MD values in DLB compared to AD patients. In DLB patients, correlation analysis showed a significant correlation between NPI hallucinations item scores and MD values in the right thalamic sub-regions projecting to parietal and occipital cortices. The present study demonstrates how thalamic connectivity alterations between higher and lower visual areas may be relevant in explaining visual hallucinations in DLB. PMID- 25113956 TI - Impact of spinal dysraphism on urinary and faecal prognosis in 25 cases of cloacal malformation. AB - OBJECTIVE: Urinary and faecal continence are key challenges goal of cloacal malformation management. Most well-known prognostic factors are the length of common channel (CC) and the presence of a sacral defect, but the impact of associated spinal dysraphism is less well documented. The aim of this study was to investigate the impact of different types of dysraphism on urinary and faecal continence in this patient population. MATERIALS AND METHODS: From 1991 to 2011, charts and office notes of 25 patients with cloacal malformation were retrospectively reviewed. At last clinic visit, urinary and faecal continence status according to Krickenbeck criteria were correlated with the length of CC, the presence of a sacral defect (sacral ratio), and the presence of different types of spinal cord dysraphism using magnetic resonance imaging (MRI) and Fisher's exact test. RESULTS: Mean follow-up was 8 years (4 months-21 years). The sacral ratio was abnormal (below 0.74) in 18 cases out of 25 (72%). MRI review showed normal spinal cord in eight out of 23 cases (Group 1), spinal cord anomaly in 15 out of 23 cases (65%) including nine cases of tethered cord complex (Group 2) and six cases of a short spinal cord (Group 3). While statistical analysis showed a difference regarding urinary prognosis between the groups (p=0.005), no significant difference was found regarding faecal prognosis. None of the six patients with short spinal cord were continent for both urinary and faecal prognosis. CONCLUSIONS: This is the first study, which highlights the impact of different types of spinal dysraphism on functional outcome in patients with cloaca. Short spinal cord seemed to carry the worst prognosis. A prospective study with a larger series is mandatory to confirm these preliminary results. PMID- 25113957 TI - Methodological approaches and magnitude of the clinical unmet need associated with amotivation in mood disorders. AB - BACKGROUND: There is growing research interest in studying motivational deficits in different neuropsychiatric disorders because these symptoms appear to be more common than originally reported and negatively impact long-term functional outcomes. However, there is considerable ambiguity in the terminology used to describe motivational deficits in the scientific literature. For the purposes of this manuscript, the term "amotivation" will be utilised in the context of mood disorders, since this is considered a more inclusive/appropriate term for this patient population. Other challenges impacting the study of amotivation in mood disorders, include: appropriate patient population selection; managing or controlling for potential confounding factors; the lack of gold-standard diagnostic criteria and assessment scales; and determination of the most appropriate study duration. METHODS: This paper summarises the search for a consensus by a group of experts in the optimal approach to studying amotivation in mood disorders. RESULTS: The consensus of this group is that amotivation in mood disorders is a legitimate therapeutic target, given the magnitude of the associated unmet needs, and that proof-of-concept studies should be conducted in order to facilitate subsequent larger investigations. The focus of this manuscript is to consider the study of amotivation, as a residual symptom of major depressive disorder (MDD) or bipolar depression (BD), following adequate treatment with a typical antidepressant or mood stabiliser/antipsychotic, respectively. DISCUSSION: There is a paucity of data studying amotivation in mood disorders. This manuscript provides general guidance on the most appropriate study design(s) and methodology to assess potential therapeutic options for the management of residual amotivation in mood disorders. PMID- 25113959 TI - Obsessive-compulsive symptoms and personal disposition, family coherence and school environment in Chinese adolescents: a resilience approach. AB - BACKGROUND: Risk factors of adolescents with obsessive-compulsive symptoms (OC) have been extensively examined, but protective resilience factors have not been explored, particularly in Chinese adolescents. AIM: This study aimed to investigate the association of resilience factors with the occurrence of OC and its symptoms in Chinese adolescents. METHOD: This study consisted of two phases. The first phase used a cross-sectional design involving a stratified clustered non-clinical sample of 3185 secondary school students. A clinical interview procedure was then employed to diagnose OC in students who had a Leyton Obsessional Inventory 'yes' score of >=15. The second phase used a case-control study design to analyse the relationship between resilience factors and OC in a matched sample of 288 adolescents with diagnosed OC relative to 246 healthy adolescents. RESULTS: Low personal disposition scores in self-fulfilment, flexibility and self-esteem, and low peer relation scores in the school environment were associated with a higher probability of having OC. Canonical correlation analysis indicated that OC symptoms were significantly associated with personal dispositions, poor peer relationships and maladaptive social life, but not to family coherence. LIMITATIONS: The study is not prospective in nature, so the causal relationship between OC occurrence and resilience factors cannot be confirmed. Second, the use of self-report instruments in personal disposition, family coherence, and school environment may be a source of error. CONCLUSIONS: Resilience factors at both the personal disposition and school environment levels are important predictors of OC symptoms and caseness. Future studies using prospective designs are needed to confirm these relationships. PMID- 25113958 TI - "Someone like us": delivering maternal mental health through peers in two South Asian contexts. AB - BACKGROUND: Peer-led psychosocial interventions are one solution to address the great paucity of skilled mental health human resources in South Asia. The aim of this study was to explore peer-delivered care for maternal depression in two diverse contexts in South Asia. METHODS: The study was carried out in the urban setting of Goa, India and rural setting in Rawalpindi, Pakistan. In total, 61 in depth interviews (IDIs) and 3 focus group discussions (FGDs), and 38 IDIs and 10 FGDs, were conducted with multiple stakeholders in urban Goa and rural Rawalpindi respectively. We used the framework approach to analyze data. RESULTS: Peers from the same community were the most preferred delivery agents of a community-based psychosocial intervention in both sites. There were contextual similarities and differences between the two sites. Preferred characteristics among peers included local, middle-aged, educated mothers with similar experiences to participants, good communication skills and a good character. Key differences between the two contexts included a greater emphasis on the peer's family social standing in rural Rawalpindi and financial incentives as motivators for individual peers in urban Goa. LIMITATIONS: Generalizability of our findings is limited to two specific contexts in a vast and diverse region. DISCUSSION: Our study demonstrates that peers have the potential to deliver maternal psychosocial interventions in low-income settings. There are contextual differences in the preferred characteristics and motivators between the sites, and these should be carefully considered in program implementation. PMID- 25113960 TI - Characteristics of deaths by suicide in Northern Ireland from 2005 to 2011 and use of health services prior to death. AB - BACKGROUND: Service presentation may offer an opportunity for intervention prior to suicide. The study aimed to examine the characteristics, disorders and service use profiles of those who had died by suicide in Northern Ireland (NI) from 2005 to 2011. METHODS: An analysis of a database of deaths by suicide and undetermined intent based on data in the NI Coronial files from 2005 to 2011 (N=1667). RESULTS: Males are three times as likely to die by suicide as females and suicide rates similar among those aged 20-60 years. Females have increased service use prior to suicide; males tend to disengage with services prior to death. Females are more likely to have recorded prior attempts, service use, diagnosis and referral. The most common health service used was primary care. LIMITATIONS: Despite the inclusion of undetermined deaths (probable suicides) a proportion of deaths by suicide remain unrecorded as such. Data on marital status and mental and physical disorders were based on information recorded by police officers from relatives, other informants and medical records. The reliability of this data may therefore be questioned. CONCLUSIONS: Primary care has an important role in suicide prevention. Gendered patterns in service use prior to death should be considered in suicide prevention programmes. It is important to strengthen clinicians' knowledge of the manifestations of suicidal ideation in males and ways of encouraging service use in males. The NI population who were exposed to the height of the violence of the conflict appear to be at increased risk of suicide as they age. PMID- 25113961 TI - [Mortality in patients with infective endocarditis treated in 2 different centers with on-site cardiac surgery. Reply]. PMID- 25113962 TI - Anti-lymphoproliferative activity of alpha-2-macroglobulin in the plasma of hibernating 13-lined ground squirrels and woodchucks. AB - Plasma from hibernating (HIB) woodchucks (Marmota monax) or 13-lined ground squirrels (Ictidomys tridecemlineatus) suppressed (3)H-thymidine uptake in mouse spleen cell cultures stimulated with Concanavalin A (ConA); plasma from non hibernating animals were only slightly inhibitory. Maximum inhibition occurred when HIB plasma was added to the cultures prior to ConA. After HPLC size exclusion chromatography of the HIB ground squirrel plasma, a single fraction (fraction-14) demonstrated inhibitory activity. Assay of fraction-14 from 8 HIB squirrels showed inhibition ranging from 13 to 95%; inhibition was correlated to the time the squirrels were exposed to cold prior to hibernation. Western blot analysis showed the factor to be a large molecular weight protein (>300 kDa), and mass spectrometry identified sequences that were 100% homologous with alpha-2 macroglobulin from humans and other species. These findings indicate a hibernation-related protein that may be responsible for immune system down regulation. PMID- 25113963 TI - Pex11a deficiency is associated with a reduced abundance of functional peroxisomes and aggravated renal interstitial lesions. AB - Although proteinuria is known to be associated with the deterioration of chronic kidney disease, the molecular basis of this mechanism is not fully understood. We previously found that Pex11a deficiency was associated with a reduction of functional peroxisomes and impaired fatty acid metabolism in hepatocytes and resulted in steatosis. Proximal tubule cells are rich in peroxisomes. We assessed whether Pex11a deficiency might result in the derangement of peroxisome systems in proximal tubule cells and the aggravation of tubulointerstitial lesions in chronic kidney disease. Histological analyses showed that the number of functional peroxisomes in proximal tubule cells was reduced in Pex11a knockout (Pex11a(-/-)) mice. To clarify whether a decrease in the number of tubular peroxisomes might aggravate interstitial lesions, we assessed 2 models in which proximal tubule cells are overloaded with fatty acids (ie, deoxycorticosterone acetate and salt hypertension and the overload of fatty acid-bound albumin). Deoxycorticosterone acetate -salt-treated Pex11a(-/-) mice exhibited greater interstitial lesions than deoxycorticosterone acetate-salt-treated wild-type mice in terms of tubular lipid accumulation, blood pressure, urinary albumin, urinary N-acetyl-beta-d-glucosaminidase, urinary 8-iso-prostane, and the histological evaluation of fibrosis and inflammation. An overload of fatty acid-bound albumin also resulted in more severe tubulointerstitial lesions in Pex11a(-/-) mice than in wild-type mice. Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, restored the abundance of peroxisomes and reduced the tubulointerstitial lesions induced by deoxycorticosterone acetate-salt hypertension. In conclusion, our results indicate that proximal tubule peroxisomes play an important role in proteinuria-induced interstitial lesions. The activation of tubular peroxisomes might be an excellent therapeutic strategy against chronic kidney disease. PMID- 25113965 TI - If I had resistant hypertension. PMID- 25113966 TI - The influence of speaker and listener variables on intelligibility of dysarthric speech. AB - This study compared changes in speech clarity as a function of speaking context. It is well documented that words produced in sentence contexts yield higher intelligibility than words in isolation for speakers with mild to moderate dysarthria. To tease apart the effect of speaker and listener variables, the current study aimed to quantify differences in word intelligibility by speaking task. Eighteen speakers with dysarthria produced a set of 25 words in isolation and within the context of a sentence. Eighteen listeners heard a randomized sample of the isolated productions, single words extracted from the sentences, and the full unaltered sentences. Listeners transcribed what they heard and rated their confidence. Words produced in isolation were just as intelligible as words produced in sentence context, both of which were more intelligible than extracted words. In other words, speakers reduced articulatory clarity in sentence production compared to isolated productions; listeners were able to cope with this reduction in clarity when they had access to contextual information but not when these cues were removed in the extracted condition. These findings are consistent with Lindblom's hypo-hyperarticulation theory in that adults with dysarthria appear to be modulating articulatory precision based on listener/task variables. This work has implications for clinical practice in that isolated word and sentence production tasks yielded equivalent intelligibility findings. LEARNING OUTCOMES: Readers will recognize that speech intelligibility is influenced by speaker and listener variables and thus the choice of speaking and listening task may yield different results. Commonly held clinical belief is that sentence production tasks yield inflated intelligibility scores but we did not find that in this sample. Findings also indicate that speakers with dysarthria may modulate articulatory clarity in response to listener needs which should be considered in treatment planning. PMID- 25113964 TI - WNK-SPAK-NCC cascade revisited: WNK1 stimulates the activity of the Na-Cl cotransporter via SPAK, an effect antagonized by WNK4. AB - The with-no-lysine (K) kinases, WNK1 and WNK4, are key regulators of blood pressure. Their mutations lead to familial hyperkalemic hypertension (FHHt), associated with an activation of the Na-Cl cotransporter (NCC). Although it is clear that WNK4 mutants activate NCC via Ste20 proline-alanine-rich kinase, the mechanisms responsible for WNK1-related FHHt and alterations in NCC activity are not as clear. We tested whether WNK1 modulates NCC through WNK4, as predicted by some models, by crossing our recently developed WNK1-FHHt mice (WNK1(+/FHHt)) with WNK4(-/-) mice. Surprisingly, the activated NCC, hypertension, and hyperkalemia of WNK1(+/FHHt) mice remain in the absence of WNK4. We demonstrate that WNK1 powerfully stimulates NCC in a WNK4-independent and Ste20 proline alanine-rich kinase-dependent manner. Moreover, WNK4 decreases the WNK1 and WNK3 mediated activation of NCC. Finally, the formation of oligomers of WNK kinases through their C-terminal coiled-coil domain is essential for their activity toward NCC. In conclusion, WNK kinases form a network in which WNK4 associates with WNK1 and WNK3 to regulate NCC. PMID- 25113967 TI - Interactions with John Gurdon--muscle as a mesodermal read-out and the community effect. AB - John Gurdon has made major contributions to developmental biology in addition to his Nobel prize winning work on nuclear reprogramming. With the frog, Xenopus, as a vertebrate model, his work on mesoderm induction led him to identify a community effect required for tissue differentiation after progenitor cells have entered a specific mesodermal programme. It is in the context of this biologically important concept, with myogenesis as an example, that we have had most scientific exchanges. Here I trace my contacts with him, from an interest in histone regulation of gene expression and reprogramming, to myogenic determination factors as markers of early mesodermal induction, to the role of the community effect in the spatiotemporal control of skeletal muscle formation. I also recount some personal anecdotes from encounters in Oxford, Paris and Cambridge, to illustrate my appreciation of him as a scientist and a colleague. PMID- 25113968 TI - Impact of urbanization level on urban air quality: a case of fine particles (PM(2.5)) in Chinese cities. AB - We examined and compared PM2.5 concentrations in urban and the surrounding regions, and further investigated the impact of urbanization on urban PM2.5 concentrations at the Chinese prefectures. Annual PM2.5 concentrations in most prefectures were greater than 10 MUg/m(3), the air quality guideline of the World Health Organization. Those prefectures were mainly distributed along the east coast and southeast of Sichuan province; The urban PM2.5 concentrations ( [Formula: see text] ) in 85 cities were greater than (>10 MUg/m(3)) those in the surrounding area. Those cities were mainly located in the Beijing-Sichuan and Shanghai-Guangxi belts. In addition, [Formula: see text] was less than (<0 MUg/m(3)) that in surrounding areas in only 41 prefectures, which were located in western China or nearby mega cities; Significant positive correlations were found between [Formula: see text] and urban population (R(2) = 0.99, P < 0.05), and between [Formula: see text] and urban second industry fraction (R(2) = 0.71, P < 0.05), suggesting that urbanization had considerable impact on PM2.5 concentrations. PMID- 25113969 TI - Pathological mechanisms underlying aneurysmal subarachnoid haemorrhage and vasospasm. AB - Aneurysmal subarachnoid haemorrhage is a cerebrovascular disease associated with an overall mortality as high as 50%. Delayed ischaemic neurologic deficits are a major contributor to this statistic, as well as the significant morbidity associated with the disease. Studies examining the pathophysiologic events causing these devastating changes in cerebral blood flow have identified several mechanisms which are thought to contribute to the development of delayed ischaemic neurological deficits, perhaps the most damaging of which are increased intracranial pressure and cerebral vasospasm. In addition, the presence of blood in the subarachnoid space can trigger a myriad of reactions resulting in increased capillary permeability, breakdown of the blood-brain barrier, and inflammation in surrounding neural tissue that adds to the devastating effects of haemorrhage. A detailed understanding of the post-haemorrhagic cellular and molecular changes that contribute to the development of cerebral ischaemia and vasospasm is imperative to the formulation of treatment and prevention options for subarachnoid haemorrhage patients. Despite a large body of research within this field, a complete understanding of rupture and vasospasm remains elusive. This study reviews the role of vasoactive substances, such as endothelin-1, as well as the histochemistry and molecular pathology of post-haemorrhage inflammation in the development of vasospasm and cerebral ischaemia. PMID- 25113971 TI - Retraction. The requirements for natural Th17 cell development are distinct from those of conventional Th17 cells. PMID- 25113970 TI - Nfil3 is crucial for development of innate lymphoid cells and host protection against intestinal pathogens. AB - The bZIP transcription factor Nfil3 (also known as E4BP4) is required for the development of natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s). We find that Nfil3 plays a critical role in the development of other mucosal tissue-associated innate lymphocytes. Type 3 ILCs (ILC3s), including lymphoid tissue inducer (LTi)-like cells, are severely diminished in both numbers and function in Nfil3-deficient mice. Using mixed bone marrow chimeric mice, we demonstrate that Nfil3 is critical for normal development of gut-associated ILC3s in a cell-intrinsic manner. Furthermore, Nfil3 deficiency severely compromises intestinal innate immune defense against acute bacterial infection with Citrobacter rodentium and Clostridium difficile. Nfil3 deficiency resulted in a loss of the recently identified ILC precursor, yet conditional ablation of Nfil3 in the NKp46(+) ILC3 subset did not perturb ILC3 numbers, suggesting that Nfil3 is required early during ILC3 development but not for lineage maintenance. Lastly, a marked defect in type 2 ILCs (ILC2s) was also observed in the lungs and visceral adipose tissue of Nfil3-deficient mice, revealing a general requirement for Nfil3 in the development of all ILC lineages. PMID- 25113973 TI - Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection. AB - Regulatory T (T reg) cells are critical for preventing autoimmunity mediated by self-reactive T cells, but their role in modulating immune responses during chronic viral infection is not well defined. To address this question and to investigate a role for T reg cells in exhaustion of virus-specific CD8 T cells, we depleted T reg cells in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). T reg cell ablation resulted in 10-100-fold expansion of functional LCMV-specific CD8 T cells. Rescue of exhausted CD8 T cells was dependent on cognate antigen, B7 costimulation, and conventional CD4 T cells. Despite the striking recovery of LCMV-specific CD8 T cell responses, T reg cell depletion failed to diminish viral load. Interestingly, T reg cell ablation triggered up-regulation of the molecule programmed cell death ligand-1 (PD-L1), which upon binding PD-1 on T cells delivers inhibitory signals. Increased PD-L1 expression was observed especially on LCMV-infected cells, and combining T reg cell depletion with PD-L1 blockade resulted in a significant reduction in viral titers, which was more pronounced than that upon PD-L1 blockade alone. These results suggest that T reg cells effectively maintain CD8 T cell exhaustion, but blockade of the PD-1 inhibitory pathway is critical for elimination of infected cells. PMID- 25113972 TI - Dissecting the complement pathway in hepatic injury and regeneration with a novel protective strategy. AB - Liver resection is commonly performed under ischemic conditions, resulting in two types of insult to the remnant liver: ischemia reperfusion injury (IRI) and loss of liver mass. Complement inhibition is recognized as a potential therapeutic modality for IRI, but early complement activation products are also essential for liver regeneration. We describe a novel site-targeted murine complement inhibitor, CR2-CD59, which specifically inhibits the terminal membrane attack complex (MAC), and we use this protein to investigate the complement-dependent balance between liver injury and regeneration in a clinical setting of pharmacological inhibition. CR2-CD59 did not impact in vivo generation of C3 and C5 activation products but was as effective as the C3 activation inhibitor CR2 Crry at ameliorating hepatic IRI, indicating that the MAC is the principle mediator of hepatic IRI. Furthermore, unlike C3 or C5 inhibition, CR2-CD59 was not only protective but significantly enhanced hepatocyte proliferation after partial hepatectomy, including when combined with ischemia and reperfusion. Remarkably, CR2-CD59 also enhanced regeneration after 90% hepatectomy and improved long-term survival from 0 to 70%. CR2-CD59 functioned by increasing hepatic TNF and IL-6 levels with associated STAT3 and Akt activation, and by preventing mitochondrial depolarization and allowing recovery of ATP stores. PMID- 25113974 TI - Tight regulation of ubiquitin-mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells. AB - Histone ubiquitination at DNA breaks is required for activation of the DNA damage response (DDR) and DNA repair. How the dynamic removal of this modification by deubiquitinating enzymes (DUBs) impacts genome maintenance in vivo is largely unknown. To address this question, we generated mice deficient for Ub-specific protease 3 (USP3; Usp3Delta/Delta), a histone H2A DUB which negatively regulates ubiquitin-dependent DDR signaling. Notably, USP3 deletion increased the levels of histone ubiquitination in adult tissues, reduced the hematopoietic stem cell (HSC) reserves over time, and shortened animal life span. Mechanistically, our data show that USP3 is important in HSC homeostasis, preserving HSC self-renewal, and repopulation potential in vivo and proliferation in vitro. A defective DDR and unresolved spontaneous DNA damage contribute to cell cycle restriction of Usp3Delta/Delta HSCs. Beyond the hematopoietic system, Usp3Delta/Delta animals spontaneously developed tumors, and primary Usp3Delta/Delta cells failed to preserve chromosomal integrity. These findings broadly support the regulation of chromatin ubiquitination as a key pathway in preserving tissue function through modulation of the response to genotoxic stress. PMID- 25113975 TI - Increased severity of respiratory infections associated with elevated anti-LPS IgG2 which inhibits serum bactericidal killing. AB - Although specific antibody induced by pathogens or vaccines is a key component of protection against infectious threats, some viruses, such as dengue, induce antibody that enhances the development of infection. In contrast, antibody dependent enhancement of bacterial infection is largely unrecognized. Here, we demonstrate that in a significant portion of patients with bronchiectasis and Pseudomonas aeruginosa lung infection, antibody can protect the bacterium from complement-mediated killing. Strains that resist antibody-induced, complement mediated killing produce lipopolysaccharide containing O-antigen. The inhibition of antibody-mediated killing is caused by excess production of O-antigen-specific IgG2 antibodies. Depletion of IgG2 to O-antigen restores the ability of sera to kill strains with long-chain O-antigen. Patients with impaired serum-mediated killing of P. aeruginosa by IgG2 have poorer respiratory function than infected patients who do not produce inhibitory antibody. We suggest that excessive binding of IgG2 to O-antigen shields the bacterium from other antibodies that can induce complement-mediated killing of bacteria. As there is significant sharing of O-antigen structure between different Gram-negative bacteria, this IgG2 mediated impairment of killing may operate in other Gram-negative infections. These findings have marked implications for our understanding of protection generated by natural infection and for the design of vaccines, which should avoid inducing such blocking antibodies. PMID- 25113976 TI - Aroclor 1254-induced genotoxicity in male gonads through oxidatively damaged DNA and inhibition of DNA repair gene expression. AB - The present study aimed to examine if multiple exposure to Aroclor 1254, a commercial mixture of polychlorinated biphenyls, had any genotoxic potential on gonads of male mice; moreover, the molecular mechanism(s) underlying this deleterious effects were elucidated. In the standard comet assay, there were significant increases in the incidence of DNA strand breaks in sperm of mice killed after 3 and 24h of last treatment with 4 mg/kg/day Aroclor 1254 for 5 weeks, while no significant difference in the DNA strand breaks was found in mice treatment with 1 and 2 mg/kg/day Aroclor 1254. The same results were also observed with spermatocyte chromosomal analysis as obvious aberrant primary spermatocytes were noted with the highest dose of Aroclor 1254 when testes were examined at 24h after the last exposure. Moreover, digestion with EndoIII resulted in significantly increased levels of DNA damage at 3 and 24h after the last exposure to 2mg/kg/day Aroclor 1254; digestion with Fpg resulted in a significant increase in DNA damage at the 3-h sampling time only as detected by oxidative comet assays. The expression of DNA repair genes p53, PARP1 and BAX were up-regulated in testes of mice killed after 3 and 24h of last administration of 4 mg/kg/day Aroclor 1254. On the other hand, no significant alteration in the expression of XRCC1 gene was observed at both sampling times. It is noteworthy that the expression of OGG1 and APEX1 was significantly decreased at 3h after the last exposure to 4 mg/kg/day Aroclor 1254. On the other hand, only the expression level of APEX1 was recovered at the 24-h sampling times. The unrecovered OGG1 may suggest that inhibition of DNA repair can be considered as a potential mode of action of Aroclor 1254 gonadal toxicity and carcinogenesis. PMID- 25113978 TI - The life cycle and occurrence of Haemaphysalis concinna (Acari: Ixodidae) under field conditions. AB - The life cycle and occurrence of Haemaphysalis concinna were investigated under field conditions from April 2012 to March 2013 in Eerguna National Natural Reserve Area situated on the China-Russia border in Inner Mongolia, China. Under natural conditions, the whole life cycle of H. concinna was allowed to complete in a natural tick habitat. With domestic rabbits supplied as hosts, the seasonal occurrence and behaviors of H. concinna were also observed in the field plot which was chosen in a natural tick habitat from April to October 2012. Results indicated that the durations of the life cycle from unfed adults to the next generation unfed adults of H. concinna ranged from 124 to 186 days (average periods of 153.1 days). The incubation time of eggs ranged from 39 to 57 days (average periods of 41.3 days), which is the longest period among the four developmental stages, followed by the premolt periods for larvae (averaged 37.7 days) and nymphs (averaged 26.0 days). The number of eggs was positively correlated with the weight of engorged females (r=0.8562, p<0.001). Eggs were laid in high amounts in the first week, subsequently, the egg amount declined gradually with small peaks occasionally observed. The female reproductive efficiency index (REI) and reproductive fitness index (RFI) was 6.2 and 4.3, respectively. Observations on the occurrence of H. concinna indicated that, in the confined plot under field conditions, larvae appeared in late May and peaked in early July, and nymphs were active during July and August. Therefore, there was an overlap in the occurrence of larvae and nymphs in both June and July. PMID- 25113977 TI - Blood feeding on large grazers affects the transmission of Borrelia burgdorferi sensu lato by Ixodes ricinus. AB - The presence of Ixodes ricinus and their associated Borrelia infections on large grazers was investigated. Carcases of freshly shot red deer, mouflon and wild boar were examined for the presence of any stage of I. ricinus. Questing ticks were collected from locations where red deer and wild boar are known to occur. Presence of Borrelia burgdorferi s.l. DNA was examined in a fraction of the collected ticks. Larvae, nymphs and adult ticks were found on the three large grazers. Red deer had the highest tick burden, with many of the nymphs and adult females attached for engorgement. Most larvae had not attached. The mean number of ticks on the animals varied from 13 to 67. Ticks were highly aggregated amongst the animals: some animals had no ticks, while others had high numbers. Larvae and nymphs were mostly found on the ears, while adult ticks were attached to the axillae. The Borrelia infection rate of questing nymphs was 8.5%. Unengorged wandering nymphs on deer had a Borrelia infection rate of 12.5%, while only 0.9% of feeding nymphs carried a Borrelia infection. The infection rate of unengorged adult male ticks was 4.5%, and that of feeding female ticks was 0.7%. The data suggest that ticks feeding on red deer and wild boar lose their Borrelia infections. The implications of the results are discussed with respect to Borrelia epidemiology and maintenance of a Borrelia reservoir as well as the role of reproductive hosts for Ixodes ricinus. PMID- 25113979 TI - Genetic variability of Anaplasma phagocytophilum in ticks and voles from Ixodes persulcatus/Ixodes trianguliceps sympatric areas from Western Siberia, Russia. AB - Anaplasma phagocytophilum is a causative agent of granulocytic anaplasmosis in different mammals. The presence of A. phagocytophilum was assayed in Ixodes persulcatus, Ixodes trianguliceps ticks and Myodes spp. voles from two I. persulcatus/I. trianguliceps sympatric areas in the Omsk region (Western Siberia, Russia). In total, A. phagocytophilum was found in 42/108 (38.9%) of vole blood samples, 13/34 (38.2%) of I. trianguliceps ticks removed from voles, 1/12 (8.3%) of I. persulcatus removed from voles, and 18/279 (7.2%) of questing I. persulcatus. GroESL operon sequence analysis of positive samples revealed three distinct A. phagocytophilum genetic groups previously identified in ticks and mammals in Russia. Genetic group 1 was found in 6/36 (16.7%) of sequenced positive blood samples; this group was previously revealed in I. persulcatus and Myodes spp. voles in different regions of Russia. Genetic group 2 was found in 30/36 (83.3%) of sequenced positive blood samples and all positive I. trianguliceps; this group was previously revealed only in Myodes spp. voles and common shrews (Sorex araneus) in I. persulcatus/I. trianguliceps sympatric areas in the Northern Ural. Genetic group 3 was found in all positive questing I. persulcatus and one blood sample; this group was previously revealed in I. persulcatus and Siberian chipmunks (Tamias sibiricus). We suppose that I. trianguliceps is the most probable vector for A. phagocytophilum of group 2. Analysis of the msp4 gene, intergenic region DOV1, and some other genetic loci has shown that isolates from different genetic groups significantly differ in all studied loci and that A. phagocytophilum of group 2 is closely related to A. phagocytophilum isolates revealed in voles and I. trianguliceps in Europe. A. phagocytophilum of groups 1 and 2 are the most similar to each other, while A. phagocytophilum of group 3 clusters with European A. phagocytophilum isolates from I. ricinus and various mammalian species. PMID- 25113980 TI - Seasonal activity patterns of the western black-legged tick, Ixodes pacificus, in relation to onset of human Lyme disease in northwestern California. AB - Seasonal activity patterns of questing western black-legged ticks, Ixodes pacificus were investigated in northwestern California. Adult I. pacificus became active in the fall (late October/early November) and their appearance was associated with the first rain of the season. Following a peak in January, the abundance of adult ticks declined such that they were rare or absent by June/July. The nymphal tick activity season occurred from January through October, and larval activity occurred from April to June, but sometimes extended into October. Thus, potentially infectious ticks (nymphs and adults) present a year-round risk of Lyme disease transmission in northwestern California. The seasonality of Lyme disease cases in humans, based on the onset of erythema migrans, mirrored tick activity patterns and was year-round in cases infected in California. Peak incidence in humans occurs from May through July, and indicates that most disease transmission is from nymphal ticks. This study demonstrates that tick activity patterns are more extended than previously recognized in northwestern California. PMID- 25113981 TI - In vitro isolation and infection intensity of Rickettsia parkeri in Amblyomma triste ticks from the Parana River Delta region, Argentina. AB - In the present study, we report the first in vitro isolation and infection intensity of Rickettsia parkeri in Amblyomma triste ticks from Argentina. No genetic differences in the molecular targets evaluated were found between R. parkeri isolates from Argentina and those R. parkeri isolates reported in Uruguay and Brazil, both obtained from A. triste. Only a minor difference was observed when compared to R. parkeri isolated from Amblyomma maculatum from United States. Moreover, the prevalence of infection by R. parkeri in ticks collected from the vegetation in the Parana Delta was high (20.4%). Interestingly, the distribution of R. parkeri infection intensity observed in A. triste ticks was distinctly bimodal, with approximately 60% of the infected ticks presenting high rickettsial loads (3.8*10(5)-4.5*10(7) ompA copies/tick) and the remainder with low rickettsial levels (5.6*10(1)-6.5*10(3) ompA copies/tick). This bimodality in R. parkeri infection intensity in ticks could determine differences in the severity of the disease, but also be important for the infection dynamics of this pathogen. Further research exploring the distribution of rickettsial infection levels in ticks, as well as its determinants and implications, is warranted. PMID- 25113982 TI - Molecular detection of tick-borne pathogens in Rhipicephalus sanguineus group ticks. AB - The Rhipicephalus sanguineus group includes some of the most widespread dog ticks, whose identification currently represents a difficult task due to the morphological similarities of these ixodid species. Recently, following the morphological and molecular characterization of tick specimens collected from dogs in all continents, Rhipicephalus sanguineus sensu lato (s.l.), Rhipicephalus turanicus and three different operational taxonomic units (namely Rhipicephalus sp. I-III) have been identified. Therefore, a comprehensive molecular study has been herein carried out to detect selected canine vector-borne pathogens (i.e., Anaplasma platys, Cercopithifilaria spp., Ehrlichia canis and Hepatozoon canis) in ticks belonging to the R. sanguineus group. A total of 204 tick specimens from dogs were examined and identified as R. sanguineus s.l. (n=81), R. turanicus (n=17), Rhipicephalus sp. I (n=66), Rhipicephalus sp. II (n=37), and Rhipicephalus sp. III (n=3). PCR assays were performed to detect mitochondrial and ribosomal target genes of Cercopithifilaria spp., A. platys, E. canis and H. canis. Out of 204 specimens examined, 2.5%, 7.4% and 21.6% scored positive to A. platys, H. canis and Cercopithifilaria spp., respectively. In addition, co infections with two pathogens (i.e., Cercopithifilaria bainae and A. platys or H. canis) were detected in four tick specimens. This study suggests a relationship between ticks belonging to the R. sanguineus group and the geographical distribution of A. platys, H. canis and Cercopithifilaria spp. However, the role of each representative tick species within the R. sanguineus group in the transmission of these canine pathogens needs to be further investigated. PMID- 25113983 TI - Differential diagnosis of three common Ixodes spp. ticks infesting songbirds of Western Europe: Ixodes arboricola, I. frontalis and I. ricinus. AB - The three most common Ixodes spp. ticks found on songbirds in Western Europe are Ixodes frontalis, I. arboricola and I. ricinus. As the latter species is a generalist, it shares several avian hosts with the two strictly ornithophilic species. Infestations of the three species can overlap in time and space, implying that tick-borne pathogens maintained by the ornithophilic ticks and their hosts could be bridged by I. ricinus to non-avian hosts. Whereas the endophilic Ixodes arboricola only occurs in cavities, I. frontalis has been collected frequently by flagging methods from understory vegetation, which is also the habitat of the field-dwelling I. ricinus. As the latter two species have rather similar morphological characteristics, they can easily be confused with each other. In this study, we present scanning electron photomicrographs of all developmental stages of I. arboricola and I. frontalis, and provide a differential diagnosis key to distinguish the ornithophilic ticks from I. ricinus. In addition, we interpreted their phylogenetic associations based on mitochondrial 16S rDNA with other Ixodes spp. ticks (I. lividus, I. turdus, I. brunneus, I. vespertilionis, I. trianguliceps, I. hexagonus, I. scapularis). PMID- 25113984 TI - Taxonomic key to nymphs of the genus Amblyomma (Acari: Ixodidae) in Argentina, with description and redescription of the nymphal stage of four Amblyomma species. AB - In the present study, we provide morphological descriptions of the nymph of Amblyomma parvitarsum, A. tonelliae, and redescriptions of A. argentinae and A. sculptum. A taxonomic key, with relevant morphological characters illustrated by scanning electron micrographs, is provided for nymphs of the 24 species of the genus Amblyomma occurring in Argentina. Species included are A. argentinae, A. aureolatum, A. auricularium, A. boeroi, A. brasiliense, A. calcaratum, A. coelebs, A. dissimile, A. dubitatum, A. incisum, A. longirostre, A. neumanni, A. nodosum, A. ovale, A. parvitarsum, A. parvum, A. pseudoconcolor, A. pseudoparvum, A. rotundatum, A. sculptum, A. tigrinum, A. tonelliae, A. triste and A. varium. Principal morphological characters used for discrimination among species are presence/absence of auriculae, cornua and festoons with tubercles, size and shape of spurs of coxa I, margin and punctations of scutum, shape of basis capituli and length of cervical grooves. The geographical distribution of each tick species included in this work is presented and the importance of an accurate determination to species level of the Amblyomma nymphs to make epidemiological inferences is also discussed. PMID- 25113985 TI - Peri-urbanisation, counter-urbanisation, and an extension of residential exposure to ticks: a clue to the trends in Lyme borreliosis incidence in the Czech Republic? AB - The incidence of tick-borne human diseases (TBD) in the Czech Republic (CZ) is on the increase, driven by infections increasingly acquired in residential locations, earlier in spring and later in autumn, and among children and the elderly. To interpret these trends, data on Lyme borreliosis (LB) incidence between 1997 and 2010 were analysed in the context of population migration flows registered in the CZ during the same period. Analysis showed that a migration stream of families with children, and of the elderly, flowed from more urbanized and densely populated localities to those more rural and less populated, where the chance of acquiring LB in the home vicinity was greater than in the urban settings. By contrast, a stream of people in the life phase between early adulthood and family formation flowed reversely, corresponding to a prominent absence of this age category from the patient spectrum. The data further showed that the more the residential exposure became prevalent, the more people were in year-round (rather than in summertime only) contact with ticks, which accounts for an extension of the cases' seasonal distribution as well as for an overall increase in case numbers. Finally, the fact that majority of the urban-to-rural migrants could be categorised as wealthier people could explain the previously noticed lack of low-status people among TBD patients in the CZ. PMID- 25113986 TI - Seasonality of immature stages of Ixodes loricatus (Acari: Ixodidae) in the Parana Delta, Argentina. AB - In this study we analyzed seasonal trends of immature stages of Ixodes loricatus parasitizing Akodon azarae (Sigmodontinae) in a locality of the Parana Delta, Buenos Aires, Argentina. The data encompassed two consecutive years and the analysis included the control of potential confounders using Generalized Linear Mixed Models (GLMM) with a negative binomial response. Larvae had within-year differences in abundance, but the peak months differed drastically between both sampling years, indicating that there was no consistent seasonal pattern. Regarding nymphs, a seasonal pattern was first apparent, but it vanished completely when potential confounders were considered, strongly suggesting that the association with season was spurious and caused by the confounders. Our results showed that the occurrence of immature I. loricatus in its hosts does not follow a distinct seasonal pattern, and highlight the usefulness of controlling for confounding and statistically assessing consistency between years when establishing tick seasonality. PMID- 25113987 TI - Serological evidence of exposure to Ehrlichia canis and Anaplasma phagocytophilum in Central Italian healthy domestic cats. AB - The aim of the present survey was to estimate the seroprevalences of Ehrlichia canis and Anaplasma phagocytophilum in the Central Italian feline population. Serum samples of 560 healthy domestic cats were examined by indirect immunofluorescence assay (IFAT), considering an antibody titre of 1:40 as cut off. Seroprevalences of 6.4% and 4.5% were found for E. canis and A. phagocytophilum, respectively. Adult, mixed breed cats showed seroprevalences higher than younger and purebred subjects, whereas no differences were observed in relation to gender and living conditions. PMID- 25113988 TI - Prevalence of antibodies against tick-borne encephalitis virus in wild game from Saxony, Germany. AB - Tick-borne encephalitis (TBE) is the most important tick-transmitted viral disease in Europe and is caused by the flavivirus TBE-virus (TBEV). In Germany TBE is unevenly distributed with the vast majority of cases occurring in the south in so-called risk areas defined as regions with an incidence of at least 1 case in 100,000 inhabitants. However, in low endemic areas with lesser TBE cases the respective risk assessment is hard to achieve. We therefore intend to use the prevalence of antibodies against TBEV in wildlife to trace TBEV endemic areas as a surrogate marker for the notification of human cases. This study was conducted in Saxony, Germany, where 34 autochthonous cases were reported since 2001, thereby not allowing a geographic allocation within the state. A total of 1,851 sera from wild boar and 35 sera from roe deer from all Saxon districts shot between April 2011 and March 2013 were screened for the presence of antibodies against TBEV. The overall seropositivity for Saxony was 10.5%. Among the wild boar sera, most positive samples could be found in the districts Meibetaen (23%) and Vogtlandkreis (20%) followed by Dresden (18%), Erzgebirgskreis and Gorlitz (both 10%). We conclude that seroprevalence studies in game animals represent a promising surrogate marker and should be considered for future determination of risk areas. Although we are currently unable to explain the discrepancy of the few human cases and the high seroprevalence in some districts, vaccination against TBE should be considered for people planning outdoor activities in Dresden, Meibetaen or Vogtlandkreis. PMID- 25113989 TI - Tick-borne pathogens in ticks collected from breeding and migratory birds in Switzerland. AB - From 2007 to 2010, 4558 migrating and breeding birds of 71 species were caught and examined for ticks in Switzerland. A total of 1205 specimens were collected; all were Ixodes ricinus ticks except one Ixodes frontalis female, which was found on a common chaffinch (Fringilla coelebs) for the first time in Switzerland. Each tick was analysed individually for the presence of Borrelia spp., Rickettsia spp., Anaplasma phagocytophilum and tick-borne encephalitis virus (TBEV). Altogether, 11.4% of birds (22 species) were infested by ticks and 39.8% of them (15 species) were carrying infected ticks. Bird species belonging to the genus Turdus were the most frequently infested with ticks and they were also carrying the most frequently infected ticks. Each tick-borne pathogen for which we tested was identified within the sample of bird-feeding ticks: Borrelia spp. (19.5%) and Rickettsia helvetica (10.5%) were predominantly detected whereas A. phagocytophilum (2%), Rickettsia monacensis (0.4%) and TBEV (0.2%) were only sporadically detected. Among Borrelia infections, B. garinii and B. valaisiana were largely predominant followed by B. afzelii, B. bavariensis, B. miyamotoi and B. burgdorferi ss. Interestingly, Candidatus Neoehrlichia mikurensis was identified in a few ticks (3.3%), mainly from chaffinches. Our study emphasizes the role of birds in the natural cycle of tick-borne pathogens that are of human medical and veterinary relevance in Europe. According to infection detected in larvae feeding on birds we implicate the common blackbird (Turdus merula) and the tree pipit (Anthus trivialis) as reservoir hosts for Borrelia spp., Rickettsia spp. and A. phagocytophilum. PMID- 25113992 TI - Multiple EPS interactions involved in the cohesion and structure of aerobic granules. AB - This study aims to clarify the biochemical nature and interactions of Extracellular Polymeric Substances (EPS) involved in the structure and cohesive properties of aerobic granules. Granules were incubated with selective hydrolytic enzymes or with chemicals and the resistance of digested granules to shear stress was evaluated. After alpha-amylase digestion, the hydrodynamic stress released macro-particles (>315 MUm) while soluble molecules (<1.5 MUm) and micro-particles (1.5-315 MUm) where mainly recovered after savinase and EDTA treatments. These data show that alpha (1-4) glucans and proteins are key polymers for granule cohesion and that divalent cationic bridging is a major aggregative mechanism. On the basis of these experiments and microscopy observations, a model is proposed for the spatial organization of EPS in the granular structure, in which alpha glucans are arranged in a capsular layer surrounding bacterial clusters while anionic proteins constitute the intercellular cement that may reinforce cohesion inside the bacterial clusters. PMID- 25113991 TI - Duodenal luminal nutrient sensing. AB - The gastrointestinal mucosa is exposed to numerous chemical substances and microorganisms, including macronutrients, micronutrients, bacteria, endogenous ions, and proteins. The regulation of mucosal protection, digestion, absorption and motility is signaled in part by luminal solutes. Therefore, luminal chemosensing is an important mechanism enabling the mucosa to monitor luminal conditions, such as pH, ion concentrations, nutrient quantity, and microflora. The duodenal mucosa shares luminal nutrient receptors with lingual taste receptors in order to detect the five basic tastes, in addition to essential nutrients, and unwanted chemicals. The recent 'de-orphanization' of nutrient sensing G protein-coupled receptors provides an essential component of the mechanism by which the mucosa senses luminal nutrients. In this review, we will update the mechanisms of and underlying physiological and pathological roles in luminal nutrient sensing, with a main focus on the duodenal mucosa. PMID- 25113993 TI - Spectrometric characterization of the effluent dissolved organic matter from an anammox reactor shows correlation between the EEM signature and anammox growth. AB - Anaerobic ammonium oxidation (anammox) is a cost-effective process to treat high strength nitrogenous wastewater. Even without organic carbon input, the effluent contains bioproducts from autotrophic and heterotrophic bacteria. In this work, excitation-emission matrix (EEM) fluorescence spectroscopy was used to characterize the effluent dissolved organic matter (EfOM) from an anammox reactor treating synthetic wastewater. Two dominant EEM components were identified as humic acid-like (component 1) and protein-like (component 2) substances with excitation/emission peaks at <240, 355, 420/464 nm and <240, 280, 330/346 nm, respectively. The presence of both compounds in the effluent was tracked during an activity recovery period (nitrogen load increased from 0.2 to 1.3 kg Nm(-3)d( 1)). The effluent concentration of both components increased during this period, indicating correlation between production and bacterial activity. The dynamics of these bioproducts during both substrate consumption and starvation phases was analyzed in batch experiments. Component 1 was only formed during substrate consumption in a rate proportional to ammonium removal and was considered an up take associated product characteristic of anammox activity. The results show that the composition of the EfOM was qualitatively and quantitatively influenced by process performance. Monitoring the EfOM could, therefore, offer a useful approach to assess anammox process performance and must be further explored. PMID- 25113994 TI - Coke dust enhances coke plant wastewater treatment. AB - Coke plant wastewater contain many toxic pollutants. Despite physico-chemical and biological treatment this specific type of wastewater has a significant impact on environment and human health. This article presents results of research on industrial adsorptive coke plant wastewater treatment. As a sorbent the coke dust, dozen times less expensive than pulverized activated carbon, was used. Treatment was conducted in three scenarios: adsorptive after full treatment with coke dust at 15 g L(-1), biological treatment enhanced with coke dust at 0.3-0.5 g L(-1) and addition of coke dust at 0.3 g L(-1) prior to the biological treatment. The enhanced biological treatment proved the most effective. It allowed additional removal of 147-178 mg COD kg(-1) of coke dust. PMID- 25113990 TI - EPICO 2.0 project. Development of educational therapeutic recommendations using the DELPHI technique on invasive candidiasis in critically ill adult patients in special situations. AB - BACKGROUND: Although there has been an improved management of invasive candidiasis in the last decade, still controversial issues remain, especially in different therapeutic critical care scenarios. AIMS: We sought to identify the core clinical knowledge and to achieve high agreement recommendations required to care for critically ill adult patients with invasive candidiasis for antifungal treatment in special situations and different scenarios. METHODS: Second prospective Spanish survey reaching consensus by the DELPHI technique, conducted anonymously by electronic e-mail in the first phase to 23 national multidisciplinary experts in invasive fungal infections from five national scientific societies including intensivists, anesthesiologists, microbiologists, pharmacologists and infectious disease specialists, answering 30 questions prepared by a coordination group after a strict review of literature in the last five years. The educational objectives spanned four categories, including peritoneal candidiasis, immunocompromised patients, special situations, and organ failures. The agreement among panelists in each item should be higher than 75% to be selected. In a second phase, after extracting recommendations from the selected items, a meeting was held with more than 60 specialists in a second round invited to validate the preselected recommendations. MEASUREMENTS AND MAIN RESULTS: In the first phase, 15 recommendations were preselected (peritoneal candidiasis (3), immunocompromised patients (6), special situations (3), and organ failures (3)). After the second round the following 13 were validated: Peritoneal candidiasis (3): Source control and early adequate antifungal treatment is mandatory; empirical antifungal treatment is recommended in secondary nosocomial peritonitis with Candida spp. colonization risk factors and in tertiary peritonitis. Immunocompromised patients (5): consider hepatotoxicity and interactions before starting antifungal treatment with azoles in transplanted patients; treat candidemia in neutropenic adult patients with antifungal drugs at least 14 days after the first blood culture negative and until normalization of neutrophils is achieved. Caspofungin, if needed, is the echinocandin with most scientific evidence to treat candidemia in neutropenic adult patients; caspofungin is also the first choice drug to treat febrile candidemia; in neutropenic patients with candidemia remove catheter. Special situations (2): in moderate hepatocellular failure, patients with invasive candidiasis use echinocandins (preferably low doses of anidulafungin and caspofungin) and try to avoid azoles; in case of possible interactions review all the drugs involved and preferably use anidulafungin. Organ failures (3): echinocandins are the safest antifungal drugs; reconsider the use of azoles in patients under renal replacement therapy; all of the echinocandins to treat patients under continuous renal replacement therapy are accepted and do not require dosage adjustment. CONCLUSIONS: Treatment of invasive candidiasis in ICU patients requires a broad range of knowledge and skills as summarized in our recommendations. These recommendations may help to optimize the therapeutic management of these patients in special situations and different scenarios and improve their outcome based on the DELPHI methodology. PMID- 25113995 TI - Development of aptamer oligonucleotides as anticoagulants and antithrombotics for cardiovascular diseases: current status. AB - Aptamers are short DNA/RNA oligonucleotides selected by a process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) based on affinity for target molecules. Since aptamers have several advantages over monoclonal antibodies, such as high specificity and affinity, flexible modification and stability, and lack of toxicity and immunogenicity, they are promising novel diagnostic and therapeutic agents. In this review, we will describe the development of aptamers against thrombin, von Willebrand factor (vWF), factor IX, and factor XII as potential anticoagulants or antithrombotics for cardiovascular diseases, especially those that have entered clinical trials. PMID- 25114006 TI - LOX-1 and mitochondria: an inflammatory relationship. PMID- 25114007 TI - Press imprint smear: a rapid, simple, and cheap method for the diagnosis of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis. AB - A modified imprint method, Press-Imprint-Smear, was compared with histopathology for the diagnosis of cutaneous leishmaniasis. Amastigotes were seen in 69 (92%) of 75 individuals in one or both assays. The Press-Imprint-Smear was positive in 85.3%, and histopathology was positive in 44%. Press-Imprint-Smear is a rapid and relatively sensitive method for the diagnosis of cutaneous leishmaniasis. PMID- 25113996 TI - CDC42 inhibition suppresses progression of incipient intestinal tumors. AB - Mutations in the APC or beta-catenin genes are well-established initiators of colorectal cancer, yet modifiers that facilitate the survival and progression of nascent tumor cells are not well defined. Using genetic and pharmacologic approaches in mouse colorectal cancer and human colorectal cancer xenograft models, we show that incipient intestinal tumor cells activate CDC42, an APC interacting small GTPase, as a crucial step in malignant progression. In the mouse, Cdc42 ablation attenuated the tumorigenicity of mutant intestinal cells carrying single APC or beta-catenin mutations. Similarly, human colorectal cancer with relatively higher levels of CDC42 activity was particularly sensitive to CDC42 blockade. Mechanistic studies suggested that Cdc42 may be activated at different levels, including at the level of transcriptional activation of the stem cell-enriched Rho family exchange factor Arhgef4. Our results indicate that early-stage mutant intestinal epithelial cells must recruit the pleiotropic functions of Cdc42 for malignant progression, suggesting its relevance as a biomarker and therapeutic target for selective colorectal cancer intervention. PMID- 25114008 TI - Chromosomal rearrangement features of Yersinia pestis strains from natural plague foci in China. AB - The Yersinia pestis chromosome contains a large variety and number of insert sequences that have resulted in frequent chromosome rearrangement events. To identify the chromosomal rearrangement features of Y. pestis strains from five typical plague foci in China and study spontaneous DNA rearrangements potentially stabilized in certain lineages of Y. pestis genomes, we examined the linking mode of locally collinear blocks (LCBs) in 30 Y. pestis strains by a polymerase chain reaction-based method. Our results suggest most strains have relatively stable chromosomal arrangement patterns, and these rearrangement characteristics also have a very close relationship with the geographical origin. In addition, some LCB linking modes are only present in specific strains. We conclude Y. pestis chromosome rearrangement patterns may reflect the genetic features of specific geographical areas and can be applied to distinguish Y. pestis isolates; furthermore, most of the rearrangement events are stable in certain lineages of Y. pestis genomes. PMID- 25114009 TI - Standardization of a TaqMan-based real-time PCR for the detection of Mycobacterium tuberculosis-complex in human sputum. AB - Real-time polymerase chain reaction (qPCR) was optimized for detecting Mycobacterium tuberculosis in sputum. Sputum was collected from patients (N = 112) with suspected pulmonary tuberculosis, tested by smear microscopy, decontaminated, and split into equal aliquots that were cultured in Lowenstein Jensen medium and tested by qPCR for the small mobile genetic element IS6110. The human ERV3 sequence was used as an internal control. 3 of 112 (3%) qPCR failed. For the remaining 109 samples, qPCR diagnosed tuberculosis in 79 of 84 patients with culture-proven tuberculosis, and sensitivity was greater than microscopy (94% versus 76%, respectively, P < 0.05). The qPCR sensitivity was similar (P = 0.9) for smear-positive (94%, 60 of 64) and smear-negative (95%, 19 of 20) samples. The qPCR was negative for 24 of 25 of the sputa with negative microscopy and culture (diagnostic specificity 96%). The qPCR had 99.5% sensitivity and specificity for 211 quality control samples including 84 non-tuberculosis mycobacteria. The qPCR cost ~5US$ per sample and provided same-day results compared with 2-6 weeks for culture. PMID- 25114010 TI - Sperm morphological features associated with chronic Chagas disease in the semen of experimentally infected dogs. AB - The presence of trypanosomatids in the reproductive systems of different mammals (causing genital lesions in the acute stage of the disease) may predispose the animals to low semen quality. However, there are no studies examining the alterations in the sperm morphological features in the chronic stage of Trypanosoma cruzi infection. Knowledge of these aspects is important to understand the other ways of transmission of the Chagas disease. Progressive motility, mass motility, concentration, and sperm morphology of 84 ejaculates of dogs that were chronically infected with T. cruzi were evaluated. Most of the findings were consistent with the reference values and with those obtained from healthy control dogs. The scrotal circumference was not correlated with spermatozoa concentration in the infected animals. In conclusion, the T. cruzi Ninoa (MHOM/MX/1994/Ninoa) strain does not cause significant alterations in the semen quality of dogs experiencing chronic Chagas disease (at concentrations of 5 * 10(4) to 1 * 10(6) parasites per animal). PMID- 25114011 TI - Preliminary study on tubuloglomerular dysfunction and evidence of renal inflammation in patients with visceral leishmaniasis. AB - Visceral leishmaniasis (VL) is a re-emerging zoonosis of worldwide distribution. Monocyte chemotactic protein-1 (MCP-1) and malondialdehyde (MDA) are inflammation biomarkers that have never been investigated in VL. The aim of this study is to investigate the association between renal abnormalities and inflammation biomarkers in VL. This study is a preliminary prospective study with 16 VL adult patients evaluated before treatment compared with a group of 13 healthy volunteers and 5 VL patients evaluated after treatment. Urinary concentration and acidification tests were performed. MCP-1 and MDA were quantified in urine. Urinary concentration deficit was found in all VL patients before (100%) and four VL patients after (80%) treatment. Urinary acidification deficit was found in nine cases before (56.2%) and two cases after (40%) treatment. Urinary MCP-1 (374 +/- 359 versus 42 +/- 29 pg/mg creatinine, P = 0.002) as well as urinary MDA (5.4 +/- 2.6 versus 2.0 +/- 0.8 MUmol/mL) showed significant differences between VL patients and controls. These data show that VL patients present urinary concentration and acidification deficit, which can persist even after specific treatment. Urinary MCP-1 and MDA are elevated in patients with VL, which suggests renal inflammation and incipient renal damage. PMID- 25114012 TI - Bacterial shedding in household contacts of cholera patients in Dhaka, Bangladesh. AB - Multiple Vibrio cholerae infections within the same household are common. Household contacts of patients with cholera were observed with daily clinical assessments and collection of rectal swab cultures for nine days after presentation of the index case. During the follow-up period, 71 (24%) of 294 household contacts developed a positive V. cholerae rectal swab, signifying bacterial shedding. The average length of bacterial shedding was 2.0 days (95% confidence interval 1.7-2.4). However, 16 (5%) of 294 contacts shed V. cholerae for >= 4 days. In a multivariate analysis, malnutrition was predictive of long term shedding (odds ratio = 1.4, 95% confidence interval = 1.3-13, P = 0.02). High rates of V. cholerae infection and bacterial shedding among household contacts of cholera patients represent an opportunity for intervention to reduce V. cholerae transmission. PMID- 25114013 TI - Development of conventional and real-time reverse transcription polymerase chain reaction assays to detect Tembusu virus in Culex tarsalis mosquitoes. AB - Tembusu virus (TMUV) is an important emerging arthropod-borne virus that may cause encephalitis in humans and has been isolated in regions of southeast Asia, including Malaysia, Thailand, and China. Currently, detection and identification of TMUV are limited to research laboratories, because quantitative rapid diagnostic assays for the virus do not exist. We describe the development of sensitive and specific conventional and real-time quantitative reverse transcription polymerase chain reaction assays for detecting TMUV RNA in infected cell culture supernatant and Culex tarsalis mosquitoes. We used this assay to document the replication of TMUV in Cx. tarsalis, where titers increased 1,000 fold 5 days after inoculation. These assays resulted in the detection of virus specific RNA in the presence of copurified mosquito nucleic acids. The use of these rapid diagnostic assays may have future applications for field pathogen surveillance and may assist in early detection, diagnosis, and control of the associated arthropod-borne pathogens. PMID- 25114015 TI - Nitrogen signalling in plant interactions with associative and endophytic diazotrophic bacteria. AB - Some beneficial plant-interacting bacteria can biologically fix N2 to plant available ammonium. Biological nitrogen fixation (BNF) is an important source of nitrogen (N) input in agriculture and represents a promising substitute for chemical N fertilizers. Diazotrophic bacteria have the ability to develop different types of root associations with different plant species. Among the highest rates of BNF are those measured in legumes nodulated by endosymbionts, an already very well documented model of plant-diazotrophic bacterial association. However, it has also been shown that economically important crops, especially monocots, can obtain a substantial part of their N needs from BNF by interacting with associative and endophytic diazotrophic bacteria, that either live near the root surface or endophytically colonize intercellular spaces and vascular tissues of host plants. One of the best reported outcomes of this association is the promotion of plant growth by direct and indirect mechanisms. Besides fixing N, these bacteria can also produce plant growth hormones, and some species are reported to improve nutrient uptake and increase plant tolerance against biotic and abiotic stresses. Thus, this particular type of plant-bacteria association consists of a natural beneficial system to be explored; however, the regulatory mechanisms involved are still not clear. Plant N status might act as a key signal, regulating and integrating various metabolic processes that occur during association with diazotrophic bacteria. This review will focus on the recent progress in understanding plant association with associative and endophytic diazotrophic bacteria, particularly on the knowledge of the N networks involved in BNF and in the promotion of plant growth. PMID- 25114014 TI - Regulation of amino acid metabolic enzymes and transporters in plants. AB - Amino acids play several critical roles in plants, from providing the building blocks of proteins to being essential metabolites interacting with many branches of metabolism. They are also important molecules that shuttle organic nitrogen through the plant. Because of this central role in nitrogen metabolism, amino acid biosynthesis, degradation, and transport are tightly regulated to meet demand in response to nitrogen and carbon availability. While much is known about the feedback regulation of the branched biosynthesis pathways by the amino acids themselves, the regulation mechanisms at the transcriptional, post transcriptional, and protein levels remain to be identified. This review focuses mainly on the current state of our understanding of the regulation of the enzymes and transporters at the transcript level. Current results describing the effect of transcription factors and protein modifications lead to a fragmental picture that hints at multiple, complex levels of regulation that control and coordinate transport and enzyme activities. It also appears that amino acid metabolism, amino acid transport, and stress signal integration can influence each other in a so-far unpredictable fashion. PMID- 25114017 TI - Recent recreational physical activity and breast cancer risk in postmenopausal women in the E3N cohort. AB - BACKGROUND: Physical activity probably protects against the risk of breast cancer after menopause, but questions remain about how rapidly and for how long this protective effect exists. METHODS: We analyzed data from 59,308 postmenopausal women (2,155 incident invasive breast cancers) followed between 1993 and 2005 (8.5 years postmenopause on average) through biennial questionnaires. Multivariable Cox models included time-varying exposure data, using levels of recreational physical activity self-reported in 1993, 1997, and 2002. RESULTS: Women with recent (within the previous 4 years) recreational physical activity levels >=12 metabolic equivalent task-hours (MET-h)/week had a lower risk of invasive breast cancer than women with lower levels [HR, 0.90; 95% confidence interval (CI), 0.82-0.99], with no apparent dose-response relation beyond 12 MET h/week. Associations did not vary significantly across ER/PR subtypes. Risk reductions were of the same magnitude order regardless of weight change, body mass index, waist circumference, or less recent (5-9 years earlier) physical activity levels. Among women with levels of physical activity >=12 MET-h/week 5 to 9 years earlier, those who became less active (<12 MET-h/week) had a significantly increased risk of breast cancer compared with those who did not (HR, 1.16; 95% CI, 1.01-1.35). And, compared with the least active women at both time points, they had no significantly decreased risk of breast cancer (HR, 1.06; 95% CI, 0.87-1.29). CONCLUSIONS: Our results suggest a decrease in risk associated with recent recreational physical activity even of modest levels. IMPACT: Starting or maintaining physical activity after menopause may be beneficial regarding breast cancer risk. PMID- 25114018 TI - Effects of coronary artery bypass grafting surgery on retinal vascular caliber, ocular pulse amplitude and retinal thickness measurements. AB - AIM: The retina and ocular vasculature are vulnerable to alterations in systemic hemodynamics, such as in open heart surgeries. Our aim was to investigate retinal vascular caliber (RVC), ocular pulse amplitude (OPA), peripapillary retinal nerve fiber layer (RNFL) and macular thickness in coronary artery bypass grafting (CABG) surgery patients. METHODS: Twenty-six patients who had a history of CABG surgery and 26 age-sex-matched healthy participants were recruited for this prospective, cross-sectional and comparative study. The RVC, peripapillary RNFL and macular thickness measurements were taken with spectral-domain optical coherence tomography. The OPA, a surrogate of pulsatile ocular blood flow, was measured with the Pascal dynamic contour tonometer. RESULTS: There were no statistically significant differences between the CABG surgery patients and the controls with regard to RVC, OPA, peripapillary RNFL thickness and macular thickness measurements (p>0.05). CONCLUSIONS: CABG surgery does not affect retinal structures and pulsatile ocular blood flow in the long-term follow-up. PMID- 25114019 TI - Is it safe to leave an ECMO circuit primed? AB - Extracorporeal membrane oxygenation (ECMO) is a means of life support for failing patients who require extreme life-saving measures due to failure of their heart, lungs or both organs. In a patient suffering cardiac arrest, the faster circulation via cardiopulmonary resuscitation (CPR) can be instituted the better the outcome is. If an ECMO circuit needs to be built and primed it may add significant minutes to the response time. The purpose of this study is to test for any growth in primed ECMO circuits at given time intervals to prove the safety of leaving an ECMO circuit primed. This, in turn, may lead to decreased response time, with an arrest and the placement of the arresting patient on ECMO. Five ECMO circuits were set up, primed and sampled for bacterial growth at 0, 24, 48 and 72 hours and then at one-week intervals, with an end point of four weeks. No bacterial growth was found at any point during the sampling process. PMID- 25114016 TI - Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 promotes systemic acquired resistance via azelaic acid and its precursor 9-oxo nonanoic acid. AB - Systemic acquired resistance (SAR) is a form of inducible disease resistance that depends on salicylic acid and its upstream regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Although local Arabidopsis thaliana defence responses activated by the Pseudomonas syringae effector protein AvrRpm1 are intact in eds1 mutant plants, SAR signal generation is abolished. Here, the SAR-specific phenotype of the eds1 mutant is utilized to identify metabolites that contribute to SAR. To this end, SAR bioassay-assisted fractionation of extracts from the wild type compared with eds1 mutant plants that conditionally express AvrRpm1 was performed. Using high-performance liquid chromatography followed by mass spectrometry, systemic immunity was associated with the accumulation of 60 metabolites, including the putative SAR signal azelaic acid (AzA) and its precursors 9-hydroperoxy octadecadienoic acid (9-HPOD) and 9-oxo nonanoic acid (ONA). Exogenous ONA induced SAR in systemic untreated leaves when applied at a 4 fold lower concentration than AzA. The data suggest that in planta oxidation of ONA to AzA might be partially responsible for this response and provide further evidence that AzA mobilizes Arabidopsis immunity in a concentration-dependent manner. The AzA fragmentation product pimelic acid did not induce SAR. The results link the C9 lipid peroxidation products ONA and AzA with systemic rather than local resistance and suggest that EDS1 directly or indirectly promotes the accumulation of ONA, AzA, or one or more of their common precursors possibly by activating one or more pathways that either result in the release of these compounds from galactolipids or promote lipid peroxidation. PMID- 25114020 TI - Commentary on: Is it safe to leave an ECMO circuit primed? PMID- 25114021 TI - One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group. AB - BACKGROUND: SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. PATIENTS AND METHODS: In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. RESULTS: At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. CONCLUSIONS: The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option. PMID- 25114022 TI - Phase II study of stereotactic body radiotherapy to primary tumor and metastatic locations in oligometastatic nonsmall-cell lung cancer patients. AB - BACKGROUND: Stereotactic body radiotherapy (SBRT) has emerged as a treatment modality in patients presenting with oligometastatic nonsmall-cell lung cancer (NSCLC). SBRT is used as a local consolidative treatment to metastatic disease sites. The majority of patients included in SBRT trials for oligometastatic NSCLC have controlled primary tumors and brain metastases. PATIENTS AND METHODS: Oligometastatic NSCLC patients with <=5 metastatic lesions were included in a prospective phase II trial to evaluate efficacy and toxicity of SBRT to all disease sites, primary tumor and metastatic locations. SBRT to a dose of 50 Gy in 10 fractions was delivered. Positron emission tomography-computed tomography (PET CT) was carried out at baseline and 3 months after SBRT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST). The progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier method from start of chemotherapy or radiotherapy. Side-effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. RESULTS: Twenty-six patients received SBRT after induction chemotherapy (n = 17) or as a primary treatment (n = 9). Median follow-up was 16.4 months. Overall metabolic response rate was 60% with seven patients (30%) achieving a complete metabolic remission and 7 (30%) a partial metabolic response. Any acute grade 2 toxicity was observed in four patients (15%) and grade 3 pulmonary toxicity in two patients (8%). Median PFS and OS were 11.2 and 23 months. The 1-year PFS and 1-year OS rate were 45% and 67%, respectively. CONCLUSION: SBRT to all disease sites, primary tumor and metastatic locations, in oligometastatic NSCLC patients produced an acceptable median PFS of 11.2 months. PMID- 25114023 TI - Ion conduction and selectivity in acid-sensing ion channel 1. AB - The ability of acid-sensing ion channels (ASICs) to discriminate among cations was assessed based on changes in conductance and reversal potential with ion substitution. Human ASIC1a was expressed in Xenopus laevis oocytes, and acid induced currents were measured using two-electrode voltage clamp. Replacement of extracellular Na(+) with Li(+), K(+), Rb(+), or Cs(+) altered inward conductance and shifted the reversal potentials consistent with a selectivity sequence of Li ~ Na > K > Rb > Cs. Permeability decreased more rapidly than conductance as a function of atomic size, with P(K)/P(Na) = 0.1 and G(K)/G(Na) = 0.7 and P(Rb)/P(Na) = 0.03 and G(Rb)/G(Na) = 0.3. Stimulation of Cl(-) currents when Na(+) was replaced with Ca(2+), Sr(2+), or Ba(2+) indicated a finite permeability to divalent cations. Inward conductance increased with extracellular Na(+) in a hyperbolic manner, consistent with an apparent affinity (K(m)) for Na(+) conduction of 25 mM. Nitrogen-containing cations, including NH4(+), NH3OH(+), and guanidinium, were also permeant. In addition to passing through the channels, guanidinium blocked Na(+) currents, implying competition for a site within the pore. The role of negative charges in an external vestibule of the pore was evaluated using the point mutation D434N. The mutant channel had a decreased single-channel conductance, measured in excised outside-out patches, and a macroscopic slope conductance that increased with hyperpolarization. It had a weakened interaction with Na(+) (K(m) = 72 mM) and a selectivity that was shifted toward larger atomic sizes. We conclude that the selectivity of ASIC1 is based at least in part on interactions with binding sites both within and internal to the outer vestibule. PMID- 25114025 TI - Three-dimensional bioprinting: new horizon for cardiac surgery. PMID- 25114024 TI - Voltage control of Ca2+ permeation through N-type calcium (Ca(V)2.2) channels. AB - Voltage-gated calcium (Ca(V)) channels deliver Ca(2+) to trigger cellular functions ranging from cardiac muscle contraction to neurotransmitter release. The mechanism by which these channels select for Ca(2+) over other cations is thought to involve multiple Ca(2+)-binding sites within the pore. Although the Ca(2+) affinity and cation preference of these sites have been extensively investigated, the effect of voltage on these sites has not received the same attention. We used a neuronal preparation enriched for N-type calcium (Ca(V)2.2) channels to investigate the effect of voltage on Ca(2+) flux. We found that the EC50 for Ca(2+) permeation increases from 13 mM at 0 mV to 240 mM at 60 mV, indicating that, during permeation, Ca(2+) ions sense the electric field. These data were nicely reproduced using a three-binding-site step model. Using roscovitine to slow Ca(V)2.2 channel deactivation, we extended these measurements to voltages <0 mV. Permeation was minimally affected at these hyperpolarized voltages, as was predicted by the model. As an independent test of voltage effects on permeation, we examined the Ca(2+)-Ba(2+) anomalous mole fraction (MF) effect, which was both concentration and voltage dependent. However, the Ca(2+) Ba(2+) anomalous MF data could not be reproduced unless we added a fourth site to our model. Thus, Ca(2+) permeation through Ca(V)2.2 channels may require at least four Ca(2+)-binding sites. Finally, our results suggest that the high affinity of Ca(2+) for the channel helps to enhance Ca(2+) influx at depolarized voltages relative to other ions (e.g., Ba(2+) or Na(+)), whereas the absence of voltage effects at negative potentials prevents Ca(2+) from becoming a channel blocker. Both effects are needed to maximize Ca(2+) influx over the voltages spanned by action potentials. PMID- 25114026 TI - Positive psychological states and health behaviors in acute coronary syndrome patients: A qualitative study. AB - Positive psychological states are linked to superior cardiac outcomes, possibly mediated through increased participation in health behaviors. Trained study staff conducted in-depth semi-structured interviews in the hospital and 3 months later for 34 patients diagnosed with an acute coronary syndrome. These interviews focused on positive psychological states, cardiac health behaviors, and their connection; the interviews were transcribed and independently coded using directed content analysis. Both optimism and positive affect were associated with completion of physical activity and healthy eating in a bidirectional manner. In contrast, gratitude, while common, was infrequently linked to completion of health behaviors. PMID- 25114028 TI - Mode of swine hepatitis E virus infection and replication in primary human hepatocytes. AB - The aim of this study was to investigate the infection and replication of swine derived hepatitis E virus (HEV) in primary cultured human hepatocytes (PHCs). Hepatocytes were cultured from the resected normal livers of patients with metastatic tumours. These cultured hepatocytes were infected with swine-derived genotype 3 or 4 HEV. Viral replication was monitored using reverse transcriptase quantitative PCR. The amount of HEV RNA increased in the culture media and cells following infection. Immunofluorescence staining implied that the spread of HEV infection in hepatocytes was attributed mainly to cell-to-cell transmission via the cell membrane. The sequences of the inoculated and propagated HEV were determined to examine whether sequence variation occurred during infection. Sequence analysis showed that there were no differences between inoculated and propagated HEV, demonstrating that in vitro infection and replication of swine HEV in PHCs occurred without sequence variation. PMID- 25114030 TI - MitraClip procedure for the treatment of a pseudo-cleft in the posterior mitral leaflet. PMID- 25114029 TI - Identification and functional analysis of inter-subunit disulfide bonds of the F protein of Helicoverpa armigera nucleopolyhedrovirus. AB - The major envelope fusion protein F of the budded virus of baculoviruses consists of two disulfide-linked subunits: an N-terminal F2 subunit and a C-terminal, membrane-anchored F1 subunit. There is one cysteine in F2 and there are 15 cysteines in F1, but their role in disulfide linking is largely unknown. In this study, the inter- and intra-subunit disulfide bonds of the Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus (HearNPV) F protein were analysed by site-directed mutagenesis. Results indicated that in a functional F protein, an inter-subunit disulfide bond exists between amino acids C108 (F2) and C241 (F1). When C241 was mutated, an alternative disulfide bond was formed between C108 and C232, rendering F non-functional. No inter-subunit bridge was observed in a double C232/C241 mutant of F1. C403 was not involved in the formation of inter subunit disulfide bonding, but mutation of this amino acid decreased viral infectivity significantly, suggesting that it might be involved in intra-subunit disulfide bonds. The influence of reductant [tris(2-carboxyethyl) phosphine (TCEP)] and free-thiol inhibitors [4-acetamido-4'-maleimidylstilbene 2,2' disulfonic acid (AMS) and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)] on the infectivity of HearNPV was tested. The results indicated that TCEP greatly decreased the infection of HzAm1 cells by HearNPV. In contrast, AMS and DTNB had no inhibitory effect on viral infectivity. The data suggested that free thiol/disulfide isomerization was not likely to play a role in viral entry and infectivity. PMID- 25114027 TI - Translating advances in cardiogenetics into effective clinical practice. AB - In this article we describe a qualitative research study in which we explored individuals' subjective experiences of both genetic testing and cardiogenetic disorders. Using a grounded theory approach, we coded and analyzed interview and focus group transcripts from 50 participants. We found that just under half of the participants who received their diagnosis during the study reported difficulty understanding information about both the purpose of genetic testing and their cardiac disease. A high level of anxiety about genetic testing and cardiac symptoms exacerbated individuals' cognitive confusion. Participants reported both positive and negative interactions with the medical community, depending on health care professionals' knowledge of cardiogenetic disorders. Overall, participants expressed a range of attitudes--positive, negative, and ambivalent--toward genetic testing. We conclude with a discussion of the barriers to achieving effective clinical care for genetic conditions and offer suggestions for improving collaborative decision making between physicians and patients. PMID- 25114031 TI - Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006-2012. AB - BACKGROUND: Reports of acute hepatitis C in young persons in the United States have increased. We examined data from national surveillance and supplemental case follow-up at selected jurisdictions to describe the US epidemiology of hepatitis C virus (HCV) infection among young persons (aged <=30 years). METHODS: We examined trends in incidence of acute hepatitis C among young persons reported to the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state, county, and urbanicity. Sociodemographic and behavioral characteristics of HCV infected young persons newly reported from 2011 to 2012 were analyzed from case interviews and provider follow-up at 6 jurisdictions. RESULTS: From 2006 to 2012, reported incidence of acute hepatitis C increased significantly in young persons 13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P = .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012 than 2006, most noticeably in nonurban counties east of the Mississippi River. Of 1202 newly reported HCV-infected young persons, 52% were female and 85% were white. In 635 interviews, 75% of respondents reported injection drug use. Of respondents reporting drug use, 75% had abused prescription opioids, with first use on average 2.0 years before heroin. CONCLUSIONS: These data indicate an emerging US epidemic of HCV infection among young nonurban persons of predominantly white race. Reported incidence was higher in 2012 than 2006 in at least 30 states, with largest increases in nonurban counties east of the Mississippi River. Prescription opioid abuse at an early age was commonly reported and should be a focus for medical and public health intervention. PMID- 25114033 TI - Editorial commentary: protease inhibitor monotherapy: safe for the CNS in durably suppressed patients? PMID- 25114034 TI - Immunogenic cell death inducers as anticancer agents. PMID- 25114036 TI - Ras in epidermal proliferation. PMID- 25114032 TI - A prospective cohort study of neurocognitive function in aviremic HIV-infected patients treated with 1 or 3 antiretrovirals. AB - BACKGROUND: The evolution of neurocognitive performance in aviremic human immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is unknown. METHODS: We prospectively included aviremic (>=1 year) HIV-positive patients, without concomitant major neurocognitive confounders, currently receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple antiretroviral therapy (ART) (n = 67) for >=1 year. We evaluated neurocognitive function (7 domains) at baseline and after 1 year. We performed analysis of covariance to evaluate if 1 additional year of exposure to monotherapy compared with triple ART had an effect on Global Deficit Score (GDS) changes after adjustment for potential confounders. We also compared the evolution of neurocognitive performance and impairment rates. RESULTS: Intention-to-treat analysis showed that monotherapy did not influence 1-year GDS change after adjustment for significant confounders (age, ethnicity, duration of therapy, hepatitis C virus status, and HOMA-IR index); the adjusted effect was -0.04 (95% confidence interval, -.14 to .05; P = .38). Neurocognitive stability was observed with monotherapy and triple therapy (GDS crude mean change, -0.09 [95% confidence interval, -.16 to -.01] vs -0.08 [-.14 to -.02]), after 1 year of follow-up, similar proportions of patients changed neurocognitive status from impaired to unimpaired (monotherapy, 4 of 18 [22.2%]; triple therapy, 4 of 19 [21.1%]; P = .91) and vice versa (monotherapy, 5 of 44 [10.2%] and triple therapy, 3 of 45 [6.3%]; P = .48). Similar results were observed in an on-treatment analysis and with use of clinical ratings instead of GDS changes. CONCLUSIONS: The number of antiretrovirals included in the ART regimen does not seem to influence the evolution of neurocognitive function in HIV-infected patients with suppressed plasma viremia. PMID- 25114037 TI - Knowledge-based computational models. PMID- 25114035 TI - Targeting lemurs against cancer metastasis. PMID- 25114039 TI - Caspase-2 regulates oncogene-induced senescence. AB - Cellular senescence is activated by numerous cellular insults, in particular those driving cancer formation, resulting in stable proliferation arrest and acquisition of specific features. By self-opposing to oncogenic stimulation, senescence is considered as a failsafe program, allowing, when functional, to inhibit cancers occurrence. Compelling evidences suggest a tumor suppressive activity of caspase-2, eventually independently of its effect on cell death. The original results described here demonstrate that this tumor suppressive activity of caspase-2 is mediated, at least in part, by its pro-senescing activity. Indeed, we have demonstrated in vitro and in vivo that loss of function of caspase-2 allows to escape oncogenic stress induced senescence. These results are discussed in the context of known tumor suppressive activity of caspase-2. PMID- 25114040 TI - Development of a real-time PCR for the detection of pathogenic Leptospira spp. in California sea lions. AB - Several real-time PCR assays are currently used for detection of pathogenic Leptospira spp.; however, few methods have been described for the successful evaluation of clinical urine samples. This study reports a rapid assay for the detection of pathogenic Leptospira spp. in California sea lions Zalophus californianus using real-time PCR with primers and a probe targeting the lipL32 gene. The PCR assay had high analytic sensitivity-the limit of detection was 3 genome copies per PCR volume using L. interrogans serovar Pomona DNA and 100% analytic specificity; it detected all pathogenic leptospiral serovars tested and none of the non-pathogenic Leptospira species (L. biflexa and L. meyeri serovar Semaranga), the intermediate species L. inadai, or the non-Leptospira pathogens tested. Our assay had an amplification efficiency of 1.00. Comparisons between the real-time PCR assay and culture isolation for detection of pathogenic Leptospira spp. in urine and kidney tissue samples from California sea lions showed that samples were more often positive by real-time PCR than by culture methods. Inclusion of an internal amplification control in the real-time PCR assay showed no inhibitory effects in PCR negative samples. These studies indicated that our real-time PCR assay has high analytic sensitivity and specificity for the rapid detection of pathogenic Leptospira species in urine and kidney tissue samples. PMID- 25114038 TI - Tumor suppressor p53 negatively regulates glycolysis stimulated by hypoxia through its target RRAD. AB - Cancer cells display enhanced glycolysis to meet their energetic and biosynthetic demands even under normal oxygen concentrations. Recent studies have revealed that tumor suppressor p53 represses glycolysis under normoxia as a novel mechanism for tumor suppression. As a common microenvironmental stress for tumors, hypoxia drives the metabolic switch from the oxidative phosphorylation to glycolysis, which is crucial for survival and proliferation of cancer cells under hypoxia. The p53's role and mechanism in regulating glycolysis under hypoxia is poorly understood. Here, we found that p53 represses hypoxia-stimulated glycolysis in cancer cells through RRAD, a newly-identified p53 target. RRAD expression is frequently decreased in lung cancer. Ectopic expression of RRAD greatly reduces glycolysis whereas knockdown of RRAD promotes glycolysis in lung cancer cells. Furthermore, RRAD represses glycolysis mainly through inhibition of GLUT1 translocation to the plasma membrane. Under hypoxic conditions, p53 induces RRAD, which in turn inhibits the translocation of GLUT1 and represses glycolysis in lung cancer cells. Blocking RRAD by siRNA greatly abolishes p53's function in repressing glycolysis under hypoxia. Taken together, our results revealed an important role and mechanism of p53 in antagonizing the stimulating effect of hypoxia on glycolysis, which contributes to p53's function in tumor suppression. PMID- 25114041 TI - Benign effect of the fish parasitic isopod Ceratothoa cf. imbricata on Selenotoca multifasciata (Scatophagidae) from Australia. AB - The tongue-biter cymothoid isopod Ceratothoa cf. imbricata is nearly ubiquitous in buccal cavities of the banded scat Selenotoca multifasciata (Scatophagidae) from Waterloo Bay, south-east Queensland. To test whether infestation affects fish growth or condition significantly, we explored parasitism and condition in 122 S. multifasciata specimens. The internal area of the buccal cavity and that occupied by ovigerous female isopods were measured, allowing the relative proportion of free internal area of the buccal cavity (PFIAO) to be calculated. Of 122 fish, 119 (97.5%) were infected; 35.3% had large female isopods, the remaining infections comprised much smaller mancae, juveniles and adult males. Mean intensity of infection was significantly correlated with fish total length (TL). In some fish, the female isopod occupied up to 80% of the buccal cavity area. There was little evidence of attachment damage in the buccal cavity; only 9 of 43 hosts analysed had restricted damage to the tissues at the points of attachment of the female isopod. Condition factor, food intensity index and stomach weight did not differ between fish with and without female C. cf. imbricata. The relative proportion of free internal area of the buccal cavity with respect to the fish total length (PFIAO/TL2 ratio) of fish infected with females correlated with food intensity and condition factor. Although the correlation was significant, the actual effect was not large because more than 70% of these 2 indices was not explained by the PFIAO/TL2 ratio (r2 < 0.3 in both cases). Despite the dramatic appearance of infestations and the high prevalence of C. cf. imbricata in the population, the near-absence of pathological alterations and the limited effect of the isopod on the condition indices and food intensity suggest that this isopod is relatively benign for S. multifasciata. PMID- 25114042 TI - Identification and analysis of three virulence-associated TonB-dependent outer membrane receptors of Pseudomonas fluorescens. AB - Pseudomonas fluorescens is a Gram-negative bacterium that can infect a wide range of farmed fish. However, very little is known about the virulence mechanism of P. fluorescens as a fish pathogen. In this study, we identified and analyzed 3 TonB dependent outer membrane receptors (TDRs) from a pathogenic P. fluorescens strain isolated from fish. In silico analysis revealed that all 3 proteins (named Tdr1 to 3) possess structural domains typical of TDRs. Quantitative real time RT-PCR analysis showed that tdr1, tdr2, and tdr3 expressions were upregulated under iron depleted conditions. Compared to the wild type, mutants defective in tdr1, tdr2, and tdr3 were retarded in growth to different extents. Infection in a turbot Scophthalmus maximus model showed that all 3 mutants were impaired in their ability to desseminate into and colonize host tissues. In addition, the tdr1 and tdr3 mutants exhibited significantly reduced virulence. When used as subunit vaccines, purified recombinant proteins of Tdr1, Tdr2, and, in particular, Tdr3 elicited significant protection in turbot against lethal P. fluorescens challenge. The vaccinated fish produced specific serum antibodies, which, when incubated with P. fluorescens, blocked infection of P. fluorescens in fish cells. Together these results indicate that Tdr1, Tdr2, and Tdr3 are iron-regulated factors that participate in bacterial virulence and induce protective immunity as subunit vaccines. PMID- 25114043 TI - Effects of experimentally induced infections of goldfish Carassius auratus with cyprinid herpesvirus 2 (CyHV-2) at various water temperatures. AB - In this study, we examined the influence of water temperature on the development of herpesviral haematopoietic necrosis (HVHN) in goldfish Carassius auratus after experimentally induced infection with cyprinid herpesvirus 2 (CyHV-2). In Expt 1, Ryukin goldfish were infected with CyHV-2 by intraperitoneal injection and maintained at 4 different water temperatures. Cumulative mortalities of the 15, 20, 25 and 30 degrees C groups were 10, 90, 90 and 60%, respectively. Therefore, the temperature range of 20-25 degrees C is considered highly permissive for HVHN. One of 6 surviving fish of the 15 degrees C group died after a rapid temperature increase to 25 degrees C at 30 d post infection. All 3 Edonishiki goldfish, co-reared with the surviving Ryukin in tanks where the water temperature was increased from 15 to 25 degrees C, died. In Expt 2, Edonishiki goldfish were exposed to CyHV-2 by bath immersion at 13 or 24 degrees C, resulting in cumulative mortalities of 0 and 87%, respectively, at 28 d post exposure. No mortality of the surviving Edonishiki in the 13 degrees C treatment was observed when the water temperature was increased to 24 degrees C. In addition, in Expt 2, no mortality was observed in any Ranchu co-reared with CyHV 2-immersed Edonishiki in the group where water temperature was increased from 13 to 24 degrees C, even after re-immersion challenge with CyHV-2. It is interesting to note that CyHV-2 DNA was detected in the kidneys of 4 of the 5 surviving Ranchu co-reared with the CyHV-2-immersed Edonishiki group where the water temperature was increased from 13 to 24 degrees C. Therefore, it is likely that the surviving Edonishiki of the 13 degrees C group were virus carriers. This study indicates that most fish infected with CyHV-2 at 13-15 degrees C acquire resistance to HVHN, but as carriers they are able to infect naive fish. PMID- 25114044 TI - Rearing practices identified as risk factors for ostreid herpesvirus 1 (OsHV-1) infection in Pacific oyster Crassostrea gigas spat. AB - Early detection of Pacific oyster spat infected with ostreid herpesvirus 1 (OsHV 1) could prevent introduction of OsHV-1-infected individuals into farming areas or onshore rearing facilities, thus reducing the risk of infection of naive oysters in such production systems. Experiments were conducted on several hundred oyster spat provided by producers in order to examine whether early rearing practices could be considered as potential risk factors for (1) OsHV-1 infection as detected by molecular methods and (2) spat mortality experimentally induced through thermal challenge. Spat groups collected on oyster beds and hatchery spat reared in growout areas during summer exhibited higher viral DNA contamination and mortalities during the trial than spat kept in onshore rearing facilities. Quantification of viral DNA before and during the trial showed that infection prevalence and intensity changed over time and revealed latent infection initially unsuspected in 3 of 10 groups. Thermal challenge induced a clear increase in the probability of detecting infected individuals, particularly for groups exhibiting significant prevalence of OsHV-1-contaminated spat prior to the challenge. The use of detection methods are discussed in relation to early rearing practices and disease control strategies. PMID- 25114045 TI - Ameson metacarcini sp. nov. (Microsporidia) infecting the muscles of Dungeness crabs Metacarcinus magister from British Columbia, Canada. AB - The Dungeness crab Metacarcinus magister supports a large and valuable fishery along the west coast of North America. Since 1998, Dungeness crabs exhibiting pink- to orange-colored joints and opaque white musculature have been sporadically observed in low prevalence from the Fraser River delta of British Columbia, Canada. We provide histological, ultrastructural, and molecular evidence that this condition is caused by a new microsporidian parasite. Crabs displaying gross symptoms were confirmed to have heavy infections of ovoid-shaped microsporidian spores (~1.8 * 1.4 um in size) within muscle bundles of the skeletal musculature. The parasite apparently infected the outer periphery of each muscle bundle, and then proliferated into the muscle fibres near the centre of each infected bundle. Light infections were observed in heart tissues, and occasionally spores were observed within the fixed phagocytes lining the blood vessels of the hepatopancreas. Transmission electron microscopy (TEM) revealed multiple life stages of a monokaryotic microsporidian parasite within the sarcoplasm of muscle fibres. Molecular analysis of partial small subunit rRNA sequence data from the new species revealed an affinity to Ameson, a genus of Microsporidia infecting marine crustaceans. Based on morphological and molecular data, the new species is distinct from Nadelspora canceri, a related microsporidian that also infects the muscles of this host. At present, little is known about the distribution, seasonality, and transmission of A. metacarcini in M. magister. PMID- 25114046 TI - Variation in black and white band disease progression in corals of the Gulf of Mannar and Palk Bay, Southeastern India. AB - Information on the progression of coral diseases and transmission to live corals is scarce despite the fact that coral disease poses one of the most lethal threats to the survival of coral reefs. In this study, in situ progression rates of lesions similar to black band disease (BBD) and white band disease (WBD) were measured in different species of corals from the Gulf of Mannar (GoM) and Palk Bay, southeastern India, during the period between January and December of 2009. Maximum progression rates of 3 and 1.6 cm mo-1 for BBD and WBD, respectively, were observed during May, when the temperature exceeded 30 degrees C. The annual progression rate was 10.9 and 4.9 cm yr-1 for BBD at GoM and Palk Bay, respectively. Significant variation in the progression rate (p < 0.001) was observed between months in all the examined species. Significant correlation between temperature and disease progression rates for BBD (R2 = 0.875, p <= 0.001) and WBD (R2 = 0.776, p <= 0.001) was recorded. Rates of disease progression were higher in Palk Bay than in GoM. This could be attributed to the higher temperature coupled with higher anthropogenic activities in Palk Bay. Severe mortality was observed due to both BBD and WBD. No sign of recovery was noticed in the disease-affected colonies at either study site. Anthropogenic activities should be checked, and further research on both the transmission and progression rate and role of the diseases in reef dynamics should be carried out to understand the causal factors in reef degradation and generate a plan to manage the reef properly. PMID- 25114047 TI - Detection of the emerging amphibian pathogens Batrachochytrium dendrobatidis and ranavirus in Russia. AB - In a population of the European common toad Bufo bufo from a rural pond in the region of Lake Glubokoe Regional Reserve in Moscow province, Russia, unexplained mass mortality events involving larvae and metamorphs have been observed over a monitoring period of >20 yr. We tested toads from this and a nearby site for the emerging amphibian pathogens Batrachochytrium dendrobatidis (Bd) and ranavirus (Rv). Both pathogens were detected, and at the rural pond site, with the above noted losses and decline in toad breeding success, 40% of B. bufo metamorphs were Bd positive, 46% were Rv positive and 20% were co-infected with both pathogens. Toad metamorphs from a neighbouring water body were also Bd and Rv positive (25 and 55%, respectively). This is the first confirmation of these pathogens in Russia. Questions remain as to the origins of these pathogens in Russia and their roles in documented mass mortality events. PMID- 25114048 TI - Rrd1p, an RNA polymerase II-specific prolyl isomerase and activator of phosphoprotein phosphatase, promotes transcription independently of rapamycin response. AB - Rrd1p (resistance to rapamycin deletion 1) has been previously implicated in controlling transcription of rapamycin-regulated genes in response to rapamycin treatment. Intriguingly, we show here that Rrd1p associates with the coding sequence of a galactose-inducible and rapamycin non-responsive GAL1 gene, and promotes the association of RNA polymerase II with GAL1 in the absence of rapamycin treatment following transcriptional induction. Consistently, nucleosomal disassembly at GAL1 is impaired in the absence of Rrd1p, and GAL1 transcription is reduced in the Deltarrd1 strain. Likewise, Rrd1p associates with the coding sequences of other rapamycin non-responsive and inducible GAL genes to promote their transcription in the absence of rapamycin treatment. Similarly, inducible, but rapamycin-responsive, non-GAL genes such as CTT1, STL1 and CUP1 are also regulated by Rrd1p. However, transcription of these inducible GAL and non-GAL genes is not altered in the absence of Rrd1p when the steady-state is reached after long transcriptional induction. Consistently, transcription of the constitutively active genes is not changed in the Deltarrd1 strain. Taken together, our results demonstrate a new function of Rrd1p in stimulation of initial rounds of transcription, but not steady-state/constitutive transcription, of both rapamycin-responsive and non-responsive genes independently of rapamycin treatment. PMID- 25114049 TI - Structure and function of TatD exonuclease in DNA repair. AB - TatD is an evolutionarily conserved protein with thousands of homologues in all kingdoms of life. It has been suggested that TatD participates in DNA fragmentation during apoptosis in eukaryotic cells. However, the cellular functions and biochemical properties of TatD in bacterial and non-apoptotic eukaryotic cells remain elusive. Here we show that Escherichia coli TatD is a Mg(2+)-dependent 3'-5' exonuclease that prefers to digest single-stranded DNA and RNA. TatD-knockout cells are less resistant to the DNA damaging agent hydrogen peroxide, and TatD can remove damaged deaminated nucleotides from a DNA chain, suggesting that it may play a role in the H2O2-induced DNA repair. The crystal structure of the apo-form TatD and TatD bound to a single-stranded three nucleotide DNA was determined by X-ray diffraction methods at a resolution of 2.0 and 2.9 A, respectively. TatD has a TIM-barrel fold and the single-stranded DNA is bound at the loop region on the top of the barrel. Mutational studies further identify important conserved metal ion-binding and catalytic residues in the TatD active site for DNA hydrolysis. We thus conclude that TatD is a new class of TIM barrel 3'-5' exonuclease that not only degrades chromosomal DNA during apoptosis but also processes single-stranded DNA during DNA repair. PMID- 25114050 TI - Hydration of protein-RNA recognition sites. AB - We investigate the role of water molecules in 89 protein-RNA complexes taken from the Protein Data Bank. Those with tRNA and single-stranded RNA are less hydrated than with duplex or ribosomal proteins. Protein-RNA interfaces are hydrated less than protein-DNA interfaces, but more than protein-protein interfaces. Majority of the waters at protein-RNA interfaces makes multiple H-bonds; however, a fraction do not make any. Those making H-bonds have preferences for the polar groups of RNA than its partner protein. The spatial distribution of waters makes interfaces with ribosomal proteins and single-stranded RNA relatively 'dry' than interfaces with tRNA and duplex RNA. In contrast to protein-DNA interfaces, mainly due to the presence of the 2'OH, the ribose in protein-RNA interfaces is hydrated more than the phosphate or the bases. The minor groove in protein-RNA interfaces is hydrated more than the major groove, while in protein-DNA interfaces it is reverse. The strands make the highest number of water-mediated H bonds per unit interface area followed by the helices and the non-regular structures. The preserved waters at protein-RNA interfaces make higher number of H-bonds than the other waters. Preserved waters contribute toward the affinity in protein-RNA recognition and should be carefully treated while engineering protein RNA interfaces. PMID- 25114051 TI - Molecular basis for the differential interaction of plant mitochondrial VDAC proteins with tRNAs. AB - In plants, the voltage-dependent anion-selective channel (VDAC) is a major component of a pathway involved in transfer RNA (tRNA) translocation through the mitochondrial outer membrane. However, the way in which VDAC proteins interact with tRNAs is still unknown. Potato mitochondria contain two major mitochondrial VDAC proteins, VDAC34 and VDAC36. These two proteins, composed of a N-terminal alpha-helix and of 19 beta-strands forming a beta-barrel structure, share 75% sequence identity. Here, using both northwestern and gel shift experiments, we report that these two proteins interact differentially with nucleic acids. VDAC34 binds more efficiently with tRNAs or other nucleic acids than VDAC36. To further identify specific features and critical amino acids required for tRNA binding, 21 VDAC34 mutants were constructed and analyzed by northwestern. This allowed us to show that the beta-barrel structure of VDAC34 and the first 50 amino acids that contain the alpha-helix are essential for RNA binding. Altogether the work shows that during evolution, plant mitochondrial VDAC proteins have diverged so as to interact differentially with nucleic acids, and this may reflect their involvement in various specialized biological functions. PMID- 25114052 TI - Quantitative models for accelerated protein dissociation from nucleosomal DNA. AB - Binding of transcription factors to their binding sites in promoter regions is the fundamental event in transcriptional gene regulation. When a transcription factor binding site is located within a nucleosome, the DNA has to partially unwrap from the nucleosome to allow transcription factor binding. This reduces the rate of transcription factor binding and is a known mechanism for regulation of gene expression via chromatin structure. Recently a second mechanism has been reported where transcription factor off-rates are dramatically increased when binding to target sites within the nucleosome. There are two possible explanations for such an increase in off-rate short of an active role of the nucleosome in pushing the transcription factor off the DNA: (i) for dimeric transcription factors the nucleosome can change the equilibrium between monomeric and dimeric binding or (ii) the nucleosome can change the equilibrium between specific and non-specific binding to the DNA. We explicitly model both scenarios and find that dimeric binding can explain a large increase in off-rate while the non-specific binding model cannot be reconciled with the large, experimentally observed increase. Our results suggest a general mechanism how nucleosomes increase transcription factor dissociation to promote exchange of transcription factors and regulate gene expression. PMID- 25114053 TI - Eukaryotic translation initiation factor eIF5 promotes the accuracy of start codon recognition by regulating Pi release and conformational transitions of the preinitiation complex. AB - eIF5 is the GTPase activating protein (GAP) for the eIF2 . GTP . Met-tRNAi (Met) ternary complex with a critical role in initiation codon selection. Previous work suggested that the eIF5 mutation G31R/SUI5 elevates initiation at UUG codons by increasing GAP function. Subsequent work implicated eIF5 in rearrangement of the preinitiation complex (PIC) from an open, scanning conformation to a closed state at AUG codons, from which Pi is released from eIF2 . GDP . Pi. To identify eIF5 functions crucial for accurate initiation, we investigated the consequences of G31R on GTP hydrolysis and Pi release, and the effects of intragenic G31R suppressors on these reactions, and on the partitioning of PICs between open and closed states. eIF5-G31R altered regulation of Pi release, accelerating it at UUG while decreasing it at AUG codons, consistent with its ability to stabilize the closed complex at UUG. Suppressor G62S mitigates both defects of G31R, accounting for its efficient suppression of UUG initiation in G31R,G62S cells; however suppressor M18V impairs GTP hydrolysis with little effect on PIC conformation. The strong defect in GTP hydrolysis conferred by M18V likely explains its broad suppression of Sui(-) mutations in numerous factors. We conclude that both of eIF5's functions, regulating Pi release and stabilizing the closed PIC conformation, contribute to stringent AUG selection in vivo. PMID- 25114054 TI - A statistical model of ChIA-PET data for accurate detection of chromatin 3D interactions. AB - Identification of three-dimensional (3D) interactions between regulatory elements across the genome is crucial to unravel the complex regulatory machinery that orchestrates proliferation and differentiation of cells. ChIA-PET is a novel method to identify such interactions, where physical contacts between regions bound by a specific protein are quantified using next-generation sequencing. However, determining the significance of the observed interaction frequencies in such datasets is challenging, and few methods have been proposed. Despite the fact that regions that are close in linear genomic distance have a much higher tendency to interact by chance, no methods to date are capable of taking such dependency into account. Here, we propose a statistical model taking into account the genomic distance relationship, as well as the general propensity of anchors to be involved in contacts overall. Using both real and simulated data, we show that the previously proposed statistical test, based on Fisher's exact test, leads to invalid results when data are dependent on genomic distance. We also evaluate our method on previously validated cell-line specific and constitutive 3D interactions, and show that relevant interactions are significant, while avoiding over-estimating the significance of short nearby interactions. PMID- 25114055 TI - A combination of computational and experimental approaches identifies DNA sequence constraints associated with target site binding specificity of the transcription factor CSL. AB - Regulation of transcription is fundamental to development and physiology, and occurs through binding of transcription factors to specific DNA sequences in the genome. CSL (CBF1/Suppressor of Hairless/LAG-1), a core component of the Notch signaling pathway, is one such transcription factor that acts in concert with co activators or co-repressors to control the activity of associated target genes. One fundamental question is how CSL can recognize and select among different DNA sequences available in vivo and whether variations between selected sequences can influence its function. We have therefore investigated CSL-DNA recognition using computational approaches to analyze the energetics of CSL bound to different DNAs and tested the in silico predictions with in vitro and in vivo assays. Our results reveal novel aspects of CSL binding that may help explain the range of binding observed in vivo. In addition, using molecular dynamics simulations, we show that domain-domain correlations within CSL differ significantly depending on the DNA sequence bound, suggesting that different DNA sequences may directly influence CSL function. Taken together, our results, based on computational chemistry approaches, provide valuable insights into transcription factor-DNA binding, in this particular case increasing our understanding of CSL-DNA interactions and how these may impact on its transcriptional control. PMID- 25114056 TI - Characterizing RNA ensembles from NMR data with kinematic models. AB - Functional mechanisms of biomolecules often manifest themselves precisely in transient conformational substates. Researchers have long sought to structurally characterize dynamic processes in non-coding RNA, combining experimental data with computer algorithms. However, adequate exploration of conformational space for these highly dynamic molecules, starting from static crystal structures, remains challenging. Here, we report a new conformational sampling procedure, KGSrna, which can efficiently probe the native ensemble of RNA molecules in solution. We found that KGSrna ensembles accurately represent the conformational landscapes of 3D RNA encoded by NMR proton chemical shifts. KGSrna resolves motionally averaged NMR data into structural contributions; when coupled with residual dipolar coupling data, a KGSrna ensemble revealed a previously uncharacterized transient excited state of the HIV-1 trans-activation response element stem-loop. Ensemble-based interpretations of averaged data can aid in formulating and testing dynamic, motion-based hypotheses of functional mechanisms in RNAs with broad implications for RNA engineering and therapeutic intervention. PMID- 25114058 TI - Can we improve the performance and reporting of investigator-initiated clinical trials? Rheumatoid arthritis as an example. AB - Investigator-initiated trials, some of which have been referred to as comparative effectiveness trials, pragmatic trials, or strategy trials, are sometimes considered to be of greater clinical importance than industry-driven trials, because they address important but unresolved clinical questions that differ from the questions asked in industry-driven trials. Regulatory authorities have provided methodological guidance for industry-driven trials for the approval of new treatments, but such guidance is less clear for investigator-initiated trials. The European League Against Rheumatism (EULAR) task force for the update of the recommendations for the management of rheumatoid arthritis has critically looked at the methodological quality and conduct of many investigator-initiated trials, and has identified a number of concerns. In this Viewpoint paper, we highlight commonly encountered issues that are discussed using examples of well known investigator-initiated trials. These issues cover three themes: (1) design choice (superiority vs non-inferiority designs); (2) statistical power and (3) convenience reporting. Since we acknowledge the importance of investigator initiated research, we also propose a shortlist of points-to-consider when designing, performing and reporting investigator-initiated trials. PMID- 25114059 TI - Estimation of heritability of different outcomes for genetic studies of TNFi response in patients with rheumatoid arthritis. AB - OBJECTIVES: Pharmacogenetic studies of tumour necrosis factor inhibitors (TNFi) response in patients with rheumatoid arthritis (RA) have largely relied on the changes in complex disease scores, such as disease activity score 28 (DAS28), as a measure of treatment response. It is expected that genetic architecture of such complex score is heterogeneous and not very suitable for pharmacogenetic studies. We aimed to select the most optimal phenotype for TNFi response using heritability estimates. METHODS: Using two linear mixed-modelling approaches (Bayz and GCTA), we estimated heritability, together with genomic and environmental correlations for the TNFi drug-response phenotype DeltaDAS28 and its separate components: Delta swollen joint count (SJC), Delta tender joint count (TJC), Delta erythrocyte sedimentation rate (ESR) and Delta visual-analogue scale of general health (VAS-GH). For this, we used genome-wide single nucleotide polymorphism (SNP) data from 878 TNFi-treated Dutch patients with RA. Furthermore, a multivariate genome-wide association study (GWAS) approach was implemented, analysing separate DAS28 components simultaneously. RESULTS: The highest heritability estimates were found for DeltaSJC (h(2)gbayz=0.76 and h(2)gGCTA=0.87) and DeltaTJC (h(2)gbayz=0.62 and h(2)gGCTA=0.82); lower heritability was found for DeltaDAS28 (h(2)gbayz=0.59 and h(2)gGCTA=0.71) while estimates for DeltaESR and DeltaVASGH were near or equal to zero. The highest genomic correlations were observed for DeltaSJC and DeltaTJC (0.49), and the highest environmental correlation was seen between DeltaTJC and DeltaVASGH (0.62). The multivariate GWAS did not generate excess of low p values as compared with a univariate analysis of DeltaDAS28. CONCLUSIONS: Our results indicate that multiple SNPs together explain a substantial portion of the variation in change in joint counts in TNFi-treated patients with RA. In conclusion, of the outcomes studied, the joint counts are most suitable for TNFi pharmacogenetics in RA. PMID- 25114061 TI - Development of a patient-reported outcome measure of tophus burden: the Tophus Impact Questionnaire (TIQ-20). AB - BACKGROUND: Tophus burden is currently measured using physical examination and imaging methods. The aim of this study was to develop a patient-reported outcome (PRO) tool to assess tophus burden in people with gout. METHODS: The responses from interviews with 25 people with tophaceous gout were used to generate items for a preliminary PRO tool. Following cognitive testing of each item, a preliminary 34-item questionnaire was administered to 103 people with tophaceous gout. Rasch analysis generated a 20-item Tophus Impact Questionnaire (TIQ-20). Test-retest reproducibility and construct validity of the TIQ-20 were assessed. RESULTS: The TIQ-20 responses fit the Rasch model and demonstrated unidimensionality, adequate precision, absence of differential item functioning and adequate person separation index. The TIQ-20 included items related to pain, activity limitation, footwear modification, participation, psychological impact and healthcare use due to tophi. In the 103 patients with tophaceous gout, floor effects were observed in 4.9% and ceiling effects in 1%. The TIQ-20 test-retest intraclass correlation coefficient was 0.76 (95% CI 0.61 to 0.85). All predicted correlations for construct validity testing were observed, including weak correlation with serum urate concentrations (r<0.30), moderate correlation with subcutaneous tophus count and dual energy CT urate volume (r=0.30-0.50), and stronger correlation with Health Assessment Questionnaire scores (r>0.50). CONCLUSIONS: We have developed a tophus-specific PRO in patients with tophaceous gout. The TIQ-20 demonstrates acceptable psychometric properties. Initial results show internal, face and construct validity, reproducibility and feasibility. Further research is required to determine responsiveness to change. PMID- 25114060 TI - Safety, tolerability and potential efficacy of injection of autologous adipose derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial. AB - BACKGROUND: In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability. METHODS: We did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy. FINDINGS: All enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynaud's phenomenon, finger oedema and quality of life was observed. INTERPRETATION: This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo controlled trial on a larger population. FUNDING: GFRS (Groupe Francophone de Recherche sur la Sclerodermie). CLINICAL TRIALS NUMBER: NCT01813279. PMID- 25114063 TI - Electrogram-gated radiofrequency ablations with duty cycle power delivery negate effects of ablation catheter motion. AB - BACKGROUND: Cardiac and respiratory movements cause catheter instability. Lateral catheter sliding over target endocardial surface can lead to poor tissue contact and unpredictable lesion formation. We describe a novel method of overcoming the effects of lateral catheter sliding movements using an electrogram-gated pulsed power ablation. METHODS AND RESULTS: All ablations were performed on a thermochromic gel myocardial phantom. Ablation settings were randomized to conventional (nongated) 30 W versus electrogram-gated at 20% duty cycle (30 W average power) at 0-, 3-, 6-, and 9-mm lateral sliding distances. Forty-eight radiofrequency ablations were performed. Deeper lesions were created in electrogram-gated versus conventional ablations at 3 mm (4.36+/-0.08 versus 4.05+/-0.17 mm; P=0.009), 6 mm (4.39+/-0.10 versus 3.44+/-0.15 mm; P<0.001), and 9 mm (4.41+/-0.06 versus 2.94+/-0.16 mm; P<<0.001) sliding distances. Electrogram gated ablations created consistent lesions at a quicker rate of growth in depth when compared with conventional ablations (P<0.001). CONCLUSIONS: (1) Lesion depth decreases and length increases in conventional ablations with greater degrees of lateral catheter movements; (2) electrogram-gated pulsed radiofrequency delivery negated the effects from lateral catheter movement by creating consistently deeper lesions irrespective of the degree of catheter movement; and (3) target lesion depths were reached significantly faster in electrogram-gated than in conventional ablations. PMID- 25114064 TI - Deafblindness: a review of the literature. AB - BACKGROUND: Deafblindness or dual sensory loss is a rare condition among young people, but more frequent among older people. Deafblindness is a heterogeneous condition that varies with regard to time of onset and degree of vision and hearing impairment, as well as communication mode, medical aetiology, and number and severity of co-morbidity. METHOD: We conducted a comprehensive review of public health issues related to deafblindness. RESULTS: Deafblindness often lead to barriers in language and communication, access to information and social interaction, which can lead to a number of health-related difficulties. Some of the reported consequences are a higher risk of depression, cognitive decline, developmental disorder in children and psychological distress. CONCLUSIONS: Deafblindness is associated with a number of health-related issues and more knowledge is needed about the impact of dual sensory loss to be able to offer the best support. PMID- 25114062 TI - Adverse remodeling of the electrophysiological response to ischemia-reperfusion in human heart failure is associated with remodeling of metabolic gene expression. AB - BACKGROUND: Ventricular arrhythmias occur more frequently in heart failure during episodes of ischemia-reperfusion although the mechanisms underlying this in humans are unclear. We assessed, in explanted human hearts, the remodeled electrophysiological response to acute ischemia-reperfusion in heart failure and its potential causes, including the remodeling of metabolic gene expression. METHODS AND RESULTS: We optically mapped coronary-perfused left ventricular wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for transplantation (D). Preparations were subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Failing hearts had exaggerated electrophysiological responses to ischemia-reperfusion, with greater action potential duration shortening (P<0.001 at 8-minute ischemia; P=0.001 at 12 minute ischemia) and greater conduction slowing during ischemia, delayed recovery of electric excitability after reperfusion (F, 4.8+/-1.8 versus D, 1.0+/-0 minutes; P<0.05), and incomplete restoration of action potential duration and conduction velocity early after reperfusion. Expression of 46 metabolic genes was probed using custom-designed TaqMan arrays, using extracted RNA from 15 failing and 9 donor hearts. Ten genes important in cardiac metabolism were downregulated in heart failure, with SLC27A4 and KCNJ11 significantly downregulated at a false discovery rate of 0%. CONCLUSIONS: We demonstrate, for the first time in human hearts, that the electrophysiological response to ischemia-reperfusion in heart failure is accelerated during ischemia with slower recovery after reperfusion. This can enhance spatial conduction and repolarization gradients across the ischemic border and increase arrhythmia susceptibility. This adverse response was associated with downregulation of expression of cardiac metabolic genes. PMID- 25114065 TI - A case of community-based fall prevention: Survey of organization and content of minor home help services in Swedish municipalities. AB - BACKGROUND: The aim of this study was to survey minor home help services provided by Swedish municipalities with the main purpose to prevent fall injuries. METHODS: If minor home help services were presented on the homepage of a municipality, an initial telephone contact was taken. Thereafter a questionnaire was administered, including questions about target groups, aim with the services, tasks included, costs and restrictions for users, budget, and experienced gains with the services. Municipalities not providing minor home help services were asked about the reason therefore and if the municipality had previously provided the services Results: The questionnaire response rate was 92%. In 191 of Sweden's 290 municipalities services were provided by, or in cooperation with, the municipality. Reasons for not providing the services were mainly financial and lack of demand. Services were more often provided in larger cities and in municipalities located in populous regions. In some municipalities services were performed by persons with functional disabilities or unemployed persons. CONCLUSIONS: Both providers and users expressed satisfaction with the services aspects expressed were that services lead to greater sense of safety and social gains the effect of the services in terms of fall prevention is yet to be proved with only a small fall-preventive effect services are probably cost-effective improved quality of life, sense of safety, and being able to offer meaningful work to otherwise unemployed persons are important aspects that might in themselves motivate the provision of minor home help services. PMID- 25114066 TI - The association between erectile dysfunction, depressive symptoms and testosterone levels among middle-aged men. AB - AIMS: The aim of this study was to investigate the association between erectile dysfunction and depressive symptoms and testosterone levels among middle-aged men at the community level. METHODS: The study population consisted of 614 men born in 1945 and living in the city of Oulu, Finland. Erectile dysfunction was assessed by the erectile function domain of the International Index of Erectile Function questionnaire and depressive symptoms by the Beck Depression Inventory. Blood samples were collected to measure testosterone and sex hormone-binding globulin level. RESULTS: After adjusting for confounders, erectile dysfunction was statistically significantly associated with depressive symptoms (risk ratio (RR) 1.66, 95% confidence interval (95% CI) 1.29-2.15), as well as with obesity (RR 1.72, 95% CI 1.12-2.62). Neither total nor free testosterone level was associated with erectile dysfunction among our study group. CONCLUSIONS: Depressive symptoms rather than testosterone levels should be taken into consideration while treating middle-aged men with erectile problems at the community level. PMID- 25114067 TI - Divorce and risk of hospital-diagnosed infectious diseases. AB - BACKGROUND: Although, divorce is considered to have a negative impact on morbidity, very little is known concerning exposure to divorce and risk of infectious diseases. We aimed to investigate the association between divorce and subsequent hospital contacts with infectious diseases. METHODS: We performed a nation-wide cohort study, including all Danish men and women (n~5.6 million) alive on the 1 January 1982 or later, and followed them for infectious disease diagnosed in hospital settings from 1982 to 2010. The association between divorce and risk of infectious diseases was evaluated through rate ratios (RRs) comparing incidence rates of infectious diseases between divorced and married pesons. RESULTS: Compared with married persons, divorced persons were overall at a 1.48 fold (RR=1.48 (95% CI: 1.47-1.50)) increased risk of hospital-diagnosed infectious diseases (RR adjusted for sex, age, period, income and education). The risk of infectious diseases was slightly more pronounced for divorced women (RR=1.54 (1.52-1.56)) than divorced men ((RR=1.42 (1.41-1.44)). The increased risk remained almost unchanged even more than 15 years after the divorce. Young age at divorce, short duration of marriage and number of divorces further increased the risk of infectious diseases, whereas number of children at time of divorce had no impact on risk of hospital-diagnosed infectious diseases following the divorce. CONCLUSIONS: Divorce appears to have a moderate but long lasting impact on the risk of infectious diseases the underlying mechanism is unknown but shared risk factors predicting divorce and infectious diseases could contribute to our findings. PMID- 25114069 TI - Inhibition of glutaminyl cyclase ameliorates amyloid pathology in an animal model of Alzheimer's disease via the modulation of gamma-secretase activity. AB - Alzheimer's disease is the most prevalent neurodegenerative disorder, characterized by neurofibrillary tangles, senile plaques, and neuron loss. Amyloid beta peptides are generated from amyloid beta precursor protein by consecutive catalysis by beta and gamma-secretases. Diversely modified forms of A have been N3pE-42 Abeta has received considerable attention as one of the major constituents of the senile plaques of AD brains due to its higher aggregation velocity, stability, and hydrophobicity compared to the full-length A. A previous study suggested that is catalyzed by glutaminyl cyclase (QC) following limited proteolysis of Abeta at the N-terminus. Here, we reveal that decreasing the QC activity via application of a QC inhibitor modulates-gamma-secretase activity, resulting in diminished plaque formation as well as reduced N3pE 42 Abeta aggregates in the subiculum of the 5XFAD mouse model of AD. This study suggests a possible novel mechanism by which QC regulates Abeta formation , namely modulation of gamma-secretase activity. PMID- 25114068 TI - Genetic determinants of disease progression in Alzheimer's disease. AB - There is a strong genetic basis for late-onset Alzheimer's disease (LOAD); thus far 22 genes/loci have been identified that affect the risk of LOAD. However, the relationships among the genetic variations at these loci and clinical progression of the disease have not been fully explored. In the present study, we examined the relationships of 22 known LOAD genes to the progression of AD in 680 AD patients recruited from the University of Pittsburgh Alzheimer's Disease Research Center. Patients were classified as "rapid progressors" if the Mini-Mental State Examination (MMSE) changed >=3 points in 12 months and "slow progressors" if the MMSE changed <=2 points. We also performed a genome-wide association study in this cohort in an effort to identify new loci for AD progression. Association analysis between single nucleotide polymorphisms (SNPs) and the progression status of the AD cases was performed using logistic regression model controlled for age, gender, dementia medication use, psychosis, and hypertension. While no significant association was observed with either APOE*4 (p = 0.94) or APOE*2 (p = 0.33) with AD progression, we found multiple nominally significant associations (p < 0.05) either within or adjacent to seven known LOAD genes (INPP5D, MEF2C, TREM2, EPHA1, PTK2B, FERMT2, and CASS4) that harbor both risk and protective SNPs. Genome-wide association analyses identified four suggestive loci (PAX3, CCRN4L, PIGQ, and ADAM19) at p < 1E-05. Our data suggest that short-term clinical disease progression in AD has a genetic basis. Better understanding of these genetic factors could help to improve clinical trial design and potentially affect the development of disease modifying therapies. PMID- 25114070 TI - Brain changes within the visuo-spatial attentional network in posterior cortical atrophy. AB - Posterior cortical atrophy (PCA) is characterized by basic visual and high order visual-spatial dysfunctions. In this study, we investigated long-distance deafferentation processes within the frontal-parietal-occipital network in ten PCA patients using a MRI-PET combined approach. Objective voxel-based [18F]FDG PET imaging measured metabolic changes in single patients. Comprehensive investigation of diffusion tensor imaging (DTI) metrics and grey-matter density with voxel-based morphometry were obtained in a subgroup of 6 patients. Fractional anisotropy in the superior longitudinal fasciculus correlated with the PET metabolic changes within the inferior parietal and frontal eye field regions. [18F]FDG-PET analysis showed in each PCA case the typical bilateral hypometabolic pattern, involving posterior temporal, parietal, and occipital cortex, with additional hypometabolic foci in the frontal eye fields. Voxel-based morphometry showed right-sided atrophy in the parieto-occipital cortex, as well as a limited temporal involvement. DTI revealed extensive degeneration of the major anterior posterior connecting fiber bundles and of commissural frontal lobe tracts. Microstructural measures in the superior longitudinal fasciculus were correlated with the PET metabolic changes within the inferior parietal and frontal eye field regions. Our results confirmed the predominant occipital-temporal and occipital parietal degeneration in PCA patients. [18F]FDG-PET and DTI-MRI combined approaches revealed neurodegeneration effects well beyond the classical posterior cortical involvement, most likely as a consequence of deafferentation processes within the occipital-parietal-frontal network that could be at the basis of visuo perceptual, visuo-spatial integration and attention deficits in PCA. PMID- 25114071 TI - Classification of non-demented patients attending a memory clinic using the new diagnostic criteria for Alzheimer's disease with disease-related biomarkers. AB - BACKGROUND: New diagnostic criteria for predemential Alzheimer's disease (AD) advocate the use of biomarkers. However, the benefit of using biomarkers has not been clearly demonstrated in clinical practice. OBJECTIVE: To investigate whether a combination of biomarkers may be helpful in classifying a population of non demented patients attending a Memory Clinic. METHODS: Sixty non-demented patients were compared with 31 healthy elderly subjects. All subjects underwent a neuropsychological examination, brain 3T magnetic resonance imaging, [F18] fluorodeoxyglucose and [F18]-flutemetamol positron emission tomography. According to their performance on memory, language, executive, and visuo-spatial domains, the patients were classified as mild cognitive impairment (amnestic, non amnestic, single, or multiple domain) or subjective cognitive impairment. Patients were then classified according to the National Institute on Aging Alzheimer's Association (NIA-AA) criteria, using the normalized mean hippocampal volume (Freesurfer), [F18]-FDG PALZAD, and [F18]-flutemetamol standard uptake value ratio (SUVr) (cut-off at the 10th percentile of controls). The standard of truth was the clinical status at study entry (patient versus control). RESULTS: The sensitivity/specificity of the clinical classification was 65/84%. The NIA-AA criteria were applicable in 85% of patients and 87% of controls. For biomarkers the best sensitivity (72%) at a fixed specificity of 84% was achieved by a combination of the three biomarkers. The clinical diagnosis was reconsidered in more than one third of the patients (42%) as a result of including the biomarker results. CONCLUSIONS: Application of the new NIA-AA AD diagnostic criteria based on biomarkers in an unselected sample of non-demented patients attending a Memory Clinic was useful in allowing for a better classification of the subjects. PMID- 25114072 TI - A candidate plasma protein classifier to identify Alzheimer's disease. AB - Biomarkers currently used in the aid for the diagnosis of Alzheimer's disease (AD) are cerebrospinal fluid (CSF) protein markers and brain neuroimaging markers. These biomarkers, however, either involve semi-invasive procedures or are costly to measure. Thus, AD biomarkers from more easily accessible body fluids, such as plasma, are very enticing. Using an aptamer-based proteomic technology, we profiled 1,129 plasma proteins of AD patients and non-demented control individuals. A 5-protein classifier for AD identification was constructed in the discovery study with excellent 10-fold cross-validation performance (90.1% sensitivity, 84.2% specificity, 87.9% accuracy, and AUC as 0.94). In an independent validation study, the classifier was applied and correctly predicted AD with 100.0% sensitivity, 80.0% specificity, and 90.0% accuracy, matching or outperforming the CSF Abeta42 and tau biomarkers whose performance were assessed in individual-matched CSF samples obtained at the same visit as plasma sample collection. Moreover, the classifier also correctly predicted mild cognitive impairment, an early pre-dementia state of the disease, with 96.7% sensitivity, 80.0% specificity, and 92.5% accuracy. These studies demonstrate that plasma proteins could be used effectively and accurately to contribute to the clinical diagnosis of AD. Although additional and more diverse cohorts are needed for further validation of the robustness, including the support of postmortem diagnosis, the 5-protein classifier appears to be a promising blood test to contribute diagnosis of AD. PMID- 25114073 TI - Increased permeability of the blood-brain barrier and Alzheimer's disease-like alterations in slit-2 transgenic mice. AB - Alzheimer's disease (AD) is a progressive neurological disorder that primarily affects memory, and its prevalence is rising. Increasing evidence suggests that dysfunction of the blood-brain barrier (BBB) may be involved in AD and other neurodegenerative diseases. Herein, we report that the permeability of the BBB is increased and that AD-like alterations are present in Slit-2 overexpressing transgenic mice. We found that behavioral change and the corresponding molecular diagnostic markers of AD, such as hippocampal neuron apoptosis, amyloid-beta (Abeta) protein deposition, and acetylcholinesterase expression, were increased in the Slit-2 transgenic mice. Moreover, the endothelial cells were dysfunctional, the size of the lateral ventricle cavity increased, and the permeability of the BBB increased. Additionally, there was an increased serum level of glutamate indicating that the BBB is related to AD. Finally, histopathological analysis of other organs in the Slit-2 overexpressing mice did not show any marked abnormalities. These findings demonstrate that Slit2 overexpression may be responsible for AD-like alterations and the increased BBB permeability in these mice. Our study provides a potential novel mechanism for the development of AD. PMID- 25114074 TI - Optimizing regions-of-interest composites for capturing treatment effects on brain amyloid in clinical trials. AB - BACKGROUND: Pittsburgh Compound B (PiB) positron emission tomography (PET) neuroimaging is a powerful research tool to characterize amyloid evolution in the brain. Quantification of amyloid load critically depends on (i) the choice of a reference region (RR) and (ii) on the selection of regions of interest (ROIs) to derive the standard uptake value ratios (SUVRs). OBJECTIVE: To evaluate the stability, i.e., negligible amyloid accumulation over time, of different RRs, and the performance of different PiB summary measures defined by selected ROIs and RRs for their sensitivity to detecting longitudinal change in amyloid burden. METHODS: To evaluate RRs, cross-sectional and longitudinal analyses of focal regional and composite measures of amyloid accumulation were carried out on the standardized PiB-PET regional data for cerebellar grey matter (CER), subcortical white matter (SWM), and pons (PON). RRs and candidate composite SUVR measures were further evaluated to select regions and develop novel composites, using standardized 2-year change from baseline. RESULTS: Longitudinal trajectories of PiB4-average of anterior cingulate (ACG), frontal cortex (FRC), parietal cortex, and precuneus-demonstrated marked variability and small change from baseline when normalized to CER, larger changes and less variability when normalized to SWM, which was further enhanced for the composite in PON-normalized settings. Novel composite PiB3, comprised of the average SUVRs of lateral temporal cortex, ACG, and FRC was created. CONCLUSION: PON and SWM appeared to be more stable RRs than the CER. PiB3 showed compelling sample size reduction and gains in power calculations for clinical trials over conventional PiB4 composite. PMID- 25114075 TI - AMPK activation ameliorates Alzheimer's disease-like pathology and spatial memory impairment in a streptozotocin-induced Alzheimer's disease model in rats. AB - Collecting evidence has shown that type 2 diabetes mellitus is a high risk factor of late-onset Alzheimer's disease (AD); the energy metabolic dysfunction is thought to be a convergent point of the two diseases. However, the underlying mechanisms of diabetes-associated AD are still unclear. In the current study, we investigated the roles of AMPK in diabetes-related AD-like pathologic features in models of intracerebroventricular-streptozotocin (ICV-STZ) animals. Rats infused with STZ (3 mg/kg, once) were followed by injection of AICAR (AMPK activator) or vehicle via ICV. We found that the level of p-AMPK (active type of AMPK) and SIRT1 activity were decreased and the level of phosphorylated tau was increased at Ser396 and Thr231 sites in ICV-STZ rats when compared with control rats. Mitochondria from ICV-STZ rats displayed a significant decrease in mitochondrial membrane potential, complex I activity, ATP level, and superoxide dismutase activity as well as an increase of reactive oxygen species production when compared with that from control rats. Meanwhile the number of apoptotic cell confirmed by cleaved caspase-3 (active type of caspase-3) staining was also stronger in ICV-STZ rats than control rats. All pathological changes including biochemistry and cognitive function could be mitigated through rescuing AMPK activity with its specific activator (AICAR) in ICV-STZ rats. Taken together, these results suggested that AMPK activation improves AD-like pathological changes via repairing mitochondrial functions in ICV-STZ rats. PMID- 25114076 TI - Amyloid-beta related memory decline is not associated with subjective or informant rated cognitive impairment in healthy adults. AB - BACKGROUND: The detection of early Alzheimer's disease (AD) can rely on subjective and informant reports of cognitive impairment. However, relationships between subjective cognitive impairment, objectively measured cognitive function, and amyloid-beta (Abeta) biomarkers remain unclear. OBJECTIVE: To determine the extent to which impairment or decline in subjective and informant rated cognitive impairment was associated with memory in healthy older adults with high Abeta. METHODS: Healthy older adults (n = 289) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were studied at baseline. Pittsburgh Compound B was used to determine Abeta status at baseline. At baseline and 18 months assessments, subjective memory impairment was assessed using the Memory Complaint Questionnaire and the Short Form of the Informant Questionnaire on Cognitive Decline in the Elderly. Cognition was measured using the Cogstate Brief Battery. RESULTS: At baseline, there were no differences between low and high Abeta groups in subjective or informant-rated cognitive impairment, depressive and anxiety symptoms, or cognitive function. Longitudinal analyses showed moderate decline in learning and working memory over the 18 months in the high Abeta group. However there was no change over time in subjective or informant rated cognitive impairment, depressive and anxiety symptoms, or cognition in either Abeta group. CONCLUSIONS: Although healthy older adults with high Abeta levels show decline in learning and working memory over 18 months, subjective or informant ratings of cognitive impairment do not change over the same period suggesting subjective cognitive impairment may have limited utility for the very early identification of AD. PMID- 25114077 TI - Default mode network connectivity patterns associated with visual processing at different stages of Parkinson's disease. AB - BACKGROUND: The default mode network (DMN) decreases its activity when switching from a resting state to a cognitive task condition, while activity of the network engaged in the given task increases. Visual processing is typically disturbed in Parkinson's disease dementia (PDD). OBJECTIVE: Using functional MRI, we studied the DMN effective connectivity patterns in PDD as compared with cognitively normal patients with Parkinson's disease (PD) and healthy controls (HC) when switching from baseline to a visual cognitive task condition. METHODS: In all, 14 PDD, 18 PD, and 18 age-matched healthy controls participated in this functional MRI study. We used a psychophysiological interaction analysis with the precuneus (PCu) as a seed. The threshold was set at p(FWE) <0.05. RESULTS: The healthy controls showed greater PCu connectivity with the bilateral middle temporal/middle occipital gyri at baseline than during the task condition. The correlation direction changed from positive to negative. Both PD and PDD showed disturbed DMN connectivity with the brain regions that are involved in bottom-up visual processing. In PD, we also found impaired integration of the areas engaged in the ventral attentional network, which might reflect specific attentional deficits observed during the early course of PD. In mild PDD, we detected increased engagement of areas involved in the dorsal attentional network, which corresponds to increased top-down control in this patient group as compared to the healthy controls. CONCLUSION: Our results show impaired dynamic interplay between large scale brain networks in PD that spread far beyond the motor system. PMID- 25114078 TI - Cholinergic subcortical hyperintensities in Alzheimer's disease patients from the Sunnybrook Dementia Study: relationships with cognitive dysfunction and hippocampal atrophy. AB - BACKGROUND: Subcortical hyperintensities within the cholinergic fiber projections (chSH) on MRI are believed to reflect cerebral small vessel disease (SVD) which may adversely impact cognition. Additionally, hippocampal atrophy represents a commonly used biomarker to support the diagnosis of Alzheimer's disease (AD). OBJECTIVE: To examine potential differences in neuropsychological test performance between AD patients (n = 234) with high and low chSH volumes and whether these differences corresponded to hippocampal atrophy. METHODS: A modified version of Lesion Explorer was used to volumetrically quantify chSH severity. The Sunnybrook Hippocampal Volumetry Tool was applied to obtain hippocampal volumes. Composite z-scores to assess executive, memory, and visuospatial functioning were generated from standardized neuropsychological test performance scores. RESULTS: Inter-method technique validation demonstrated a high degree of correspondence with the Cholinergic Pathways Hyperintensities Scale (n = 40, rho = 0.84, p < 0.001). After adjusting for brain atrophy, disease severity, global SH volumes, and demographic variables, multivariate analyses revealed a significant group difference, with the high chSH group demonstrating poorer memory function compared to the low chSH group (p = 0.03). A significant difference was found between low and high chSH groups in total (p < 0.05) and left (p < 0.01) hippocampal volume. CONCLUSION: These results suggest degradation of the cholinergic projections due to strategic SVD may independently contribute to memory dysfunction and hippocampal atrophy. Future studies examining subcortical vasculopathy in the cholinergic pathways may have implications on the development of therapeutic strategies for dementia and SVD. PMID- 25114079 TI - Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis. AB - BACKGROUND: Research into Ginkgo biloba has been ongoing for many years, while the benefit and adverse effects of Ginkgo biloba extract EGb761 for cognitive impairment and dementia has been discussed controversially. OBJECTIVE: To discuss new evidence on the clinical and adverse effects of standardized Ginkgo biloba extract EGb761 for cognitive impairment and dementia. METHODS: MEDLINE, EMBASE, Cochrane, and other relevant databases were searched in March 2014 for eligible randomized controlled trials of Ginkgo biloba EGb761 therapy in patients with cognitive impairment and dementia. RESULTS: Nine trials met our inclusion criteria. Trials were of 22-26 weeks duration and included 2,561 patients in total. In the meta-analysis, the weighted mean differences in change scores for cognition were in favor of EGb761 compared to placebo (-2.86, 95%CI -3.18; 2.54); the standardized mean differences in change scores for activities in daily living (ADLs) were also in favor of EGb761 compared to placebo (-0.36, 95%CI 0.44; -0.28); Peto OR showed a statistically significant difference from placebo for Clinicians' Global Impression of Change (CGIC) scale (1.88, 95%CI 1.54; 2.29). All these benefits are mainly associated with EGb761 at a dose of 240 mg/day. For subgroup analysis in patients with neuropsychiatric symptoms, 240 mg/day EGb761 improved cognitive function, ADLs, CGIC, and also neuropsychiatric symptoms with statistical superiority than for the whole group. For the Alzheimer's disease subgroup, the main outcomes were almost the same as the whole group of patients with no statistical superiority. Finally, safety data revealed no important safety concerns with EGb761. CONCLUSIONS: EGb761 at 240 mg/day is able to stabilize or slow decline in cognition, function, behavior, and global change at 22-26 weeks in cognitive impairment and dementia, especially for patients with neuropsychiatric symptoms. PMID- 25114081 TI - Transmembrane protein 106B gene (TMEM106B) variability and influence on progranulin plasma levels in patients with Alzheimer's disease. AB - We carried out an association study of transmembrane protein 106B gene (TMEM106B) rs1020004 A/G, rs6966915C/T, and rs1990622 A/G in a population of 656 patients with Alzheimer's disease (AD) and 619 controls, and tested whether the rs1990622 influences plasma progranulin levels. No differences in allele and genotype distribution were observed between cases and controls, even stratifying according to APOE status (p > 0.05). No differences in progranulin plasma levels were found between carriers of the rs1990622 and non-carriers. TMEM106b variability does not influence AD risk or plasma levels. Replication, preferably in a population with pathological confirmation, is required to confirm these results. PMID- 25114082 TI - Characterizing topological patterns in amnestic mild cognitive impairment by quantitative water diffusivity. AB - Mean diffusivity (MD) derived from diffusion tensor imaging has shown its ability to assess the microscopic structural integrity damage of gray matter in amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer's disease (AD). However, little is known about the small world topology networks constructed by cortical MD in cognitive disease. In this work, we measured the cortical MD in the entire brain in patients with aMCI (n = 30) and AD (n = 30) compared with cognitive-normal (CNs) controls (n = 30), and then constructed the cortical diffusivity network by using graph-theoretical analysis. Compared with CNs, patients with aMCI and AD showed abnormal small-world property of cortical diffusivity networks (higher degree of clustering and longer path length), reflecting a less optimal topological organization. Moreover, the mean degree of connections of network in aMCI patients was characterized by lower than CNs but higher than AD. In addition, 11 hub regions were identified by negative correlations between MD and the score of Montreal Cognitive Assessment after multiple regression analysis, including bilateral hippocampi and related limbic system. Among those hub regions, the connectivity of the right olfactory cortex and middle orbital gyrus to the rest of brain regions were disrupted earlier than the other 9 regions in aMCI when compared to CN. In conclusion, the change of cortical diffusivity in topological network organization, mean degree of connections, and disrupted hub regions in aMCI may serve to identify patients in the prodromal stage of AD and reflect microstructural deterioration of neurodegeneration. PMID- 25114080 TI - Overexpression of heme oxygenase 1 causes cognitive decline and affects pathways for tauopathy in mice. AB - The stress protein heme oxygenase-1 (HO-1) is upregulated and co-localizes to pathological features, including tauopathies in the brains of individuals with Alzheimer's disease. However, the relationship between HO-1 and Alzheimer's disease remains unclear. In our previous research, the long-term overexpression of HO-1 was shown to promote tau aggregation by inducing tau phosphorylation in the mouse brain. In this study, we found that the long-term overexpression of HO 1 led to cognitive decline in transgenic mice, as determined by the water maze test, and that HO-1 can affect two pathways for tauopathy. Through one pathway, HO-1 promotes the expression of CDK5 by accumulating reactive oxygen species, which are produced by HO-1 downstream products of iron in neuro2a cell lines and mouse brain. Through the second pathway, HO-1 induces tau truncation at D421 in vivo and in vitro. Clearly, there is a HO-1-dependent mechanism responsible for tau protein phosphorylation and tau truncation in vivo and in vitro. Taken together, our results suggest that HO-1 plays an important role in the disease process of tauopathies in AD. PMID- 25114084 TI - Contributions of a risk assessment approach to the prevention of Alzheimer's disease and dementia. AB - The development and integration of risk assessment and clinical risk management for Alzheimer's disease (AD) and dementia is a rapidly emerging field of research and practice. At present, risk management is the only available approach with potential for a large impact on the projected rates of dementia, given population aging. This review describes six available risk assessment tools, including those developed specifically for AD and those for dementia. These tools differ along several important dimensions, including whether they (a) include clinical measures, (b) require a clinician's ratings, (c) are predominantly self-report, (d) are independently validated, and (e) are available online. A narrative review of recently identified risk factors not included in these instruments is included, indicating future directions for risk assessment. Finally, consideration is given to the prioritization of risk advice according to the ease of risk modification and the potential for synergies among risk factors. PMID- 25114085 TI - Cognitively-based methods of enhancing and maintaining functioning in those at risk of Alzheimer's disease. AB - Projections indicate that the prevalence of Alzheimer's disease (AD) and other dementias will increase two to three fold in the coming decades. As a result, there has been considerable interest in identifying methods that maintain or enhance cognitive functioning in these older adults. Existing pharmacological agents are limited in this respect and disease-modifying agents are years away from being available. Cognitively based interventions (i.e., cognitive training, cognitive rehabilitation) hold particular promise for maximizing patients' functioning, are relatively inexpensive, and have virtually no side effects. Everyday life is complex and multifaceted, which means that a personalized approach is essential for maximizing and prolonging functioning in each patient. Unfortunately, little is known about the factors contributing to such an approach. The current review first identifies several lifestyle factors that have been shown to be neuroprotective as well as risk factors that may ultimately contribute to the efficacy of different cognitive intervention techniques. There is a critical need to understand the conditions under which individual techniques are effective; an issue examined through characteristic examples across the AD spectrum. While limited at this time, there is some evidence of the long-term benefits of cognitive intervention. We conclude by describing several critical areas of investigation and proposing a clinically oriented framework for both furthering cognitive intervention research and providing patient-centered care. PMID- 25114083 TI - A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation. AB - SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic cause of Paget disease of bone and of amyotrophic lateral sclerosis. More recently, SQSTM1 mutations were identified in few families with frontotemporal dementia. We report a new family carrying SQSTM1 mutation and presenting with a clinical phenotype of speech apraxia or atypical behavioral disorders, associated with early visuo-contructional deficits. This study further supports the implication of SQSTM1 in frontotemporal dementia, and enlarges the phenotypic spectrum associated with SQSTM1 mutations. PMID- 25114086 TI - Tofu intake is associated with poor cognitive performance among community dwelling elderly in China. AB - Tofu is a soy product which is commonly consumed in Asian countries, such as China and Indonesia. Several studies found negative associations of high tofu consumption with cognitive function in older Asian populations. However, the effect of tofu on cognitive function remains disputed as it was not found in Western populations. In the present study, the effect of weekly tofu intake on cognitive performance was investigated in an observational cross sectional study of 517 Chinese elderly from Shanghai. Similar to earlier studies, results showed that a higher weekly intake of tofu was associated with worse memory performance using the Hopkins Verbal Learning Test (beta = -0.10, p = 0.01) after controlling for age, gender, education, being vegetarian, and weekly intake of fruit/juice, green vegetables, and orange/red vegetables. Furthermore, among older elderly (>=68 years of age), high tofu intake increased the risk of cognitive impairment indicative of dementia (OR = 1.27, 95% CI = 0.99-1.64, p = 0.04), after adjusting for all covariates. Consumption of meat and green vegetables independently also reduced risk of dementia. To conclude, high intake of tofu was negatively related to cognitive performance among community-dwelling elderly in China. Similar findings were reported in Indonesia and in Japanese Americans in the US. These findings suggest that the effect of tofu on cognition in elderly should be further investigated. PMID- 25114087 TI - The Florence VAS-COG clinic: a model for the care of patients with cognitive and behavioral disturbances consequent to cerebrovascular diseases. AB - BACKGROUND AND OBJECTIVE: Services dedicated to patients with cognitive and behavioral consequences of cerebrovascular diseases are not well established. In this paper, we report on the general organization of such a service (the Florence VAS-COG Clinic) after 9 years of activity, updating a previous work related to the first 5 years. METHODS: The Florence VAS-COG clinic, started in 2006, is an outpatient service dedicated to the assessment and follow-up of patients with cerebrovascular diseases and related cognitive, psychiatric, and behavioral disturbances. The staff involved in the clinic is composed of certified neurologists, one neuropsychologist, and neurology residents. The diagnostic protocol includes detailed personal and family history, general and neurologic examinations, and functional, neuropsychological, and neuroimaging assessment. After this work-up, comprehensive diagnoses are made. RESULTS: From January 2006 to March 2014, 600 patients (mean age 67.3 years +/- 13.9; 52% females) have been evaluated in the clinic. Cognitive impairment, including mild cognitive impairment and dementia, mainly of vascular origin, was the most common (36.4%) diagnostic category, followed by suspected or confirmed familial micro-angiopathy (35.8%). Compared to the first years of activity, we are now facing the need of augmenting the number of visits due to increasing request and to better implement the multidisciplinarity of the team. Efforts are currently directed towards the definition of management protocols in pharmacological and non-pharmacological strategies. CONCLUSIONS: The establishment of a VAS-COG clinic represents an important step for the appreciation of the patient clinical needs and for the implementation of screening, diagnostic, and treatment options in the field of the neuropsychiatric consequences of cerebrovascular diseases. PMID- 25114089 TI - In-house heart-brain clinics to reduce Alzheimer's disease incidence. AB - The incidence rate in Alzheimer's disease (AD) is expected to quadruple worldwide by 2050. To limit this impending socio-medical calamity, a fulcrum change from how AD is presently managed is crucial. The present approach has not averted the stress of AD on medical resources nor reduced the already cost-strained government health care programs. Since substantial evidence indicates that sporadic AD is directly associated with vascular risk factors, a strategic plan is proposed to target this association and markedly reduce the onset of AD. This plan would establish in-house heart-brain clinics devoted to identifying, detecting, and preventing the progression of vascular risk factors that predispose to cognitive impairment and development of AD. The heart-brain clinics would be staffed with a multidisciplinary group of neurologists, psychologists, neuroradiologists, cardiovascular specialists, and technical personnel Their goal would be to apply and interpret non-invasive, cost-effective multidiagnostic testing of heart and brain function in outpatient asymptomatic and symptomatic patients at risk of dementia. Multidiagnostic testing would permit better risk stratification, medical decision-making, and a tailored intervention of patients at-risk of dementia than the present monotherapeutic approach. Personalized intervention, moreover, should achieve better patient compliance and outcome through periodic follow-up visits to the clinics where the medical plan of action could be monitored and modified as needed. Multidisciplinary heart-brain clinics will be costly at first but eventually should become cost-effective while providing an invaluable medical service to an aging population and possibly extending years of full-health lived in those at risk of dementia. PMID- 25114090 TI - The interaction of APOE genotype by age in amnestic mild cognitive impairment: a voxel-based morphometric study. AB - The apolipoprotein E (APOE) gene has been confirmed as the major genetic risk factor for the conversion of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). The present study was to assess whether there was a specific interaction of APOE by the aging process on brain morphology in aMCI. The analysis of gray matter (GM) voxel-based morphometry was performed in 85 aMCI and 100 healthy controls (HC). A significant interaction of APOE genotype by age on GM volume was found in the left calcarine, the left insula, and the left medial frontal gyrus in aMCI. GM volume in aMCI decreased significantly with epsilon 2-carriers < epsilon3/epsilon3 < epsilon4-carriers in above brain regions (except the left insula) while there was only a reduced tendency in HC. The multivariate regression analysis showed the well-known negative relationship for epsilon4-carriers and the positive relationship for epsilon2-carriers (except the left insula), while no correlations were found for epsilon3/epsilon3 between age and GM volumes on above brain regions. Moreover, the reduced GM volumes in the left calcarine and insula correlated with the impairment of visuo-spatial cognition and episodic memory in epsilon4- and epsilon2-carriers but not epsilon3/epsilon3, respectively. These results suggest that the APOE epsilon4 and epsilon2 alleles have the opposing effects on brain morphology across the spectrum of cognitive aging. Moreover, the interaction of APOE by age on brain morphology may accelerate the pathological progression of late-life cognitive decline in aMCI with epsilon4-carriers and delay the possible conversion from aMCI with epsilon2-carriers to AD. PMID- 25114091 TI - PTEN hamartoma tumour syndrome: early tumour development in children. AB - OBJECTIVE: The aim of this study was to report the earliest age of diagnosis of common clinical findings in children with PTEN hamartoma tumour syndrome (PHTS). DESIGN: Medical records of children with PHTS were reviewed; data included growth measurements, presence or absence of specific clinical manifestations and tumours, and documented ages of diagnosis. SETTING: Children with PHTS evaluated at Boston Children's Hospital from 1996 to 2011. PATIENTS: The cohort included 34 children diagnosed with PHTS via genetic testing, under the age of 21 years. Of these, 23 were male and 11 female. The mean age at their last documented clinical evaluation was 13.6 years. The mean follow-up time was 7.5 years. RESULTS: Macrocephaly and developmental/intellectual disability were consistent findings. Pigmented penile macules were noted in all males examined for this finding. Thyroid nodules, found in half the children screened with ultrasound, were diagnosed as early as at 5 years of age. Thyroid carcinoma, identified in 12% of the children in this cohort, was diagnosed as early as at 7 years of age. Other tumours included renal cell carcinoma diagnosed at 11 years of age and granulosa cell tumour of the ovary and colonic ganglioneuroma, each diagnosed at 16 years of age. CONCLUSIONS: Specific clinical findings and tumours are characteristic in children with PHTS. Tumour development occurs in young children with this condition, which necessitates early surveillance, especially of the thyroid. PMID- 25114088 TI - Common mechanisms of Alzheimer's disease and ischemic stroke: the role of protein kinase C in the progression of age-related neurodegeneration. AB - Ischemic stroke and Alzheimer's disease (AD), despite being distinct disease entities, share numerous pathophysiological mechanisms such as those mediated by inflammation, immune exhaustion, and neurovascular unit compromise. An important shared mechanistic link is acute and chronic changes in protein kinase C (PKC) activity. PKC isoforms have widespread functions important for memory, blood brain barrier maintenance, and injury repair that change as the body ages. Disease states accelerate PKC functional modifications. Mutated forms of PKC can contribute to neurodegeneration and cognitive decline. In some cases the PKC isoforms are still functional but are not successfully translocated to appropriate locations within the cell. The deficits in proper PKC translocation worsen stroke outcome and amyloid-beta toxicity. Cross talk between the innate immune system and PKC pathways contribute to the vascular status within the aging brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension disrupt normal communication between the two systems. The focus of this review is to highlight what is known about PKC function, how isoforms of PKC change with age, and what additional alterations are consequences of stroke and AD. The goal is to highlight future therapeutic targets that can be applied to both the treatment and prevention of neurologic disease. Although the pathology of ischemic stroke and AD are different, the similarity in PKC responses warrants further investigation, especially as PKC-dependent events may serve as an important connection linking age-related brain injury. PMID- 25114094 TI - A review of anomalous origination of a coronary artery from an opposite sinus of Valsalva (ACAOS) impact on major adverse cardiovascular events based on coronary computerized tomography angiography: a 6-year single center review. AB - BACKGROUND: Anomalous origination of a coronary artery from an opposite sinus of Valsalva (ACAOS) is a rare finding that is typically found on autopsy in a person with sudden cardiac death or during routine cardiovascular testing. The true prevalence is unknown for this reason. There is also question to the specific anatomy of the anomalies themselves and how best to correct them. METHODS: We performed a retrospective chart review of all coronary computed tomography angiography (CCTA) studies to evaluate the incidence of all-cause mortality, nonfatal myocardial infarction, stroke and late revascularization (>90 days following CCTA) from January 2005 until July 2012. We describe the origin of the artery, its course, slit-like appearance and treatment in this population. RESULTS: We reviewed 1518 CCTA reports and identified 22 patients with ACAOS with an incidence of 1.4% of our original study population over a review period of 6 years with a resultant median follow-up period of 25 months [interquartile range (IQR)25,75 12-34 months]. The indication for CCTA was for chest pain in the majority of patients (73%). We had one patient undergo surgical repair and one with coronary bypass grafting for unrelated symptomatic coronary artery disease. CONCLUSION: ACAOS continues to be a rare but presumed fatal condition in subsets identified to carry high risk features. As the characteristics of the anomalous vessels that increase risk are still debated, over an intermediate to long follow up in a single large center, none of the different anomalous findings with varying degrees of high risk findings were associated with sudden death. PMID- 25114095 TI - A rare cause of cardiogenic shock: variant angina. AB - Variant angina (VA) is a clinical syndrome caused by spontaneous vasospasm of the epicardial coronary artery which is characterized by episodes of angina. Endothelial dysfunction and neurohormonal hyperactivity are important factors in pathogenesis of VA. Although patient prognosis is good, VA may be one of the reasons of sudden cardiac death (SCD) in case of persistent ST segment elevation and malignant arrhythmias. Therefore, early treatment of VA is crucial for prevention of malignant arrhythmias and SCD. In this case report we describe a case of VA presented with cardiogenic shock and malignant ventricular arrhythmia. PMID- 25114092 TI - Direct measurement of the mechanical work during translocation by the ribosome. AB - A detailed understanding of tRNA/mRNA translocation requires measurement of the forces generated by the ribosome during this movement. Such measurements have so far remained elusive and, thus, little is known about the relation between force and translocation and how this reflects on its mechanism and regulation. Here, we address these questions using optical tweezers to follow translation by individual ribosomes along single mRNA molecules, against an applied force. We find that translocation rates depend exponentially on the force, with a characteristic distance close to the one-codon step, ruling out the existence of sub-steps and showing that the ribosome likely functions as a Brownian ratchet. We show that the ribosome generates ~13 pN of force, barely sufficient to unwind the most stable structures in mRNAs, thus providing a basis for their regulatory role. Our assay opens the way to characterizing the ribosome's full mechano chemical cycle. PMID- 25114096 TI - Elucidation of primary metabolic pathways in Aspergillus species: orphaned research in characterizing orphan genes. AB - Primary metabolism affects all phenotypical traits of filamentous fungi. Particular examples include reacting to extracellular stimuli, producing precursor molecules required for cell division and morphological changes as well as providing monomer building blocks for production of secondary metabolites and extracellular enzymes. In this review, all annotated genes from four Aspergillus species have been examined. In this process, it becomes evident that 80-96% of the genes (depending on the species) are still without verified function. A significant proportion of the genes with verified metabolic functions are assigned to secondary or extracellular metabolism, leaving only 2-4% of the annotated genes within primary metabolism. It is clear that primary metabolism has not received the same attention in the post-genomic area as many other research areas--despite its role at the very centre of cellular function. However, several methods can be employed to use the metabolic networks in tandem with comparative genomics to accelerate functional assignment of genes in primary metabolism. In particular, gaps in metabolic pathways can be used to assign functions to orphan genes. In this review, applications of this from the Aspergillus genes will be examined, and it is proposed that, where feasible, this should be a standard part of functional annotation of fungal genomes. PMID- 25114099 TI - Co-author responsibility: Distinguishing between the moral and epistemic aspects of trust. PMID- 25114097 TI - Adipose stromal cells differentiate along a smooth muscle lineage pathway upon endothelial cell contact via induction of activin A. AB - RATIONALE: Adipose stromal cells (ASC) are therapeutically potent progenitor cells that possess properties of pericytes. In vivo, ASC in combination with endothelial cells (EC) establish functional multilayer vessels, in which ASC form the outer vessel layer and differentiate into mural cells. OBJECTIVE: To identify factors responsible for ASC differentiation toward the smooth muscle cell phenotype via interaction with EC. METHODS AND RESULTS: An in vitro model of EC cocultivation with ASC was used, in which EC organized into vascular cords, accompanied by ASC migration toward EC and upregulation of alpha-smooth muscle actin, SM22alpha, and calponin expression. Conditioned media from EC-ASC, but not from EC cultures, induced smooth muscle cell protein expression in ASC monocultures. EC-ASC cocultivation induced marked accumulation of activin A but not transforming growth factor-beta1 in conditioned media. This was attributed to induction of activin A expression in ASC on contact with EC. Although transforming growth factor-beta and activin A were individually sufficient to initiate expression of smooth muscle cell antigens in ASC, only activin A IgG blocked the effect of EC-ASC conditioned media. Although transforming growth factor-beta was able to induce activin A expression in ASC, in cocultures this induction was transforming growth factor-beta independent. In EC-ASC cocultures, activin A IgG or ALK4/5/7 receptor inhibitors blocked expression of alpha-smooth muscle actin in ASC in the absence of direct EC-cord contact, but this inhibition was circumvented in ASC by direct EC contact. CONCLUSIONS: EC initiate a smooth muscle cell differentiation program in adjacent ASC and propagate this differentiation in distant ASC by induction of activin A expression. PMID- 25114098 TI - Epigenetic modification at Notch responsive promoters blunts efficacy of inducing notch pathway reactivation after myocardial infarction. AB - RATIONALE: The Notch pathway plays a key role in stimulating mammalian cardiomyocyte proliferation during development and in the early postnatal life; in adult zebrafish, reactivation of this pathway is also essential to drive cardiac regeneration after injury. OBJECTIVE: We wanted to assess efficacy of Notch pathway stimulation in neonatal and adult hearts as a means to induce cardiac regeneration after myocardial infarction in mice. METHODS AND RESULTS: In early postnatal life, cardiomyocyte exit from the cell cycle was paralleled by decreased Notch signaling and the establishment of a repressive chromatin environment at Notch-responsive genes, characterized by recruitment of the polycomb group enhancer of zeste homolog 2 methyltransferase and the acquisition of the histone 3 Lysine 27 trimethylation histone mark, as detected by chromatin immunoprecipitation. Forced Notch pathway activation by adenoassociated virus gene transfer of activated Notch1 or its ligand Jagged1 expanded the proliferative capacity of neonatal cardiomyocytes; this correlated with increased transcription of Notch target genes and maintenance of an open chromatin conformation at their promoters. The same adenoassociated virus vectors, however, were largely ineffective in stimulating cardiac repair after myocardial infarction in adult mice, despite optimal and long-lasting transgene expression. Analysis of Notch-responsive promoters in adult cardiomyocytes showed marks of repressed chromatin and irreversible CpG DNA methylation. Induction of adult cardiomyocyte re-entry into the cell cycle with microRNAs was independent from Notch pathway reactivation. CONCLUSIONS: Notch pathway activation is crucial in regulating cardiomyocyte proliferation during the early postnatal life, but it is largely ineffective in driving cardiac regeneration in adults, because of permanent epigenetic modification at Notch-responsive promoters. PMID- 25114100 TI - Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid induced leucine zipper expression in dendritic cells. AB - Autoimmune neuroinflammation, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity, is believed to result from immune tolerance dysfunction leading to demyelination and substantial neurodegeneration. We previously showed that CNS restricted expression of hepatocyte growth factor (HGF), a potent neuroprotective factor, reduced CNS inflammation and clinical deficits associated with EAE. In this study, we demonstrate that systemic HGF treatment ameliorates EAE through the development of tolerogenic dendritic cells (DCs) with high expression levels of glucocorticoid-induced leucine zipper (GILZ), a transcriptional repressor of gene expression and a key endogenous regulator of the inflammatory response. RNA interference-directed neutralization of GILZ expression by DCs suppressed the induction of tolerance caused by HGF. Finally, adoptive transfer of HGF-treated DCs from wild-type but not GILZ gene-deficient mice potently mediated functional recovery in recipient mice with established EAE through effective modulation of autoaggressive T cell responses. Altogether, these results show that by inducing GILZ in DCs, HGF reproduces the mechanism of immune regulation induced by potent immunomodulatory factors such as IL-10, TGF-beta1, and glucocorticoids and therefore that HGF therapy may have potential in the treatment of autoimmune dysfunctions. PMID- 25114101 TI - Innate immune cell CD45 regulates lymphopenia-induced T cell proliferation. AB - The leukocyte-specific tyrosine phosphatase, CD45, severely impacts T cell development and activation by modulating TCR signaling. CD45-deficient (CD45KO) mice have reduced peripheral T cell numbers where CD8 T cells are underrepresented. In this article, we show that CD45KO mice are unable to support efficient homeostatic proliferation, affecting CD8 T cells more than CD4 T cells. Using CD45-RAG1 double-deficient (45RAGKO) mice, we show that lymphopenia-induced proliferation (LIP) of CD45-sufficient T cells is defective in a host environment lacking CD45 on innate immune cells. We identify two deficiencies in the 45RAGKO mice that affect LIP. One involves CD11c(+) cells and the second the production of IL-7 by lymphoid stromal cells. CD45KO dendritic cells were not defective in foreign Ag-induced T cell proliferation, yet CD45KO CD11c(+) cells were unable to rescue the spontaneous LIP in the 45RAGKO mice. This was in contrast with the CD45-sufficient CD11c(+) cells that partially rescued this spontaneous proliferation and did so without affecting IL-7 levels. The absence of CD45 also led to reduced IL-7 production by lymphoid stromal cells, suggesting an indirect effect of CD45 on innate immune cells in influencing IL-7 production by lymphoid stromal cells. These findings demonstrate a novel role for CD45 on innate immune cells in promoting lymphopenia-induced T cell proliferation and suggest that innate immune cells may communicate with stromal cells to regulate IL-7 production. PMID- 25114102 TI - Chlamydia trachomatis inhibits inducible NO synthase in human mesenchymal stem cells by stimulating polyamine synthesis. AB - Chlamydia trachomatis is considered the most common agent of sexually transmitted disease worldwide. As an obligate intracellular bacterium, it relies on the host for survival. Production of NO is an effective antimicrobial defense mechanism of the innate immune system. However, whether NO is able to arrest chlamydial growth remains unclear. Similarly, little is known about the mechanisms underlying subversion of cellular innate immunity by C. trachomatis. By analyzing protein and mRNA expression in infected human mesenchymal stem cells, combined with RNA interference and biochemical assays, we observed that infection with C. trachomatis led to downregulated expression of inducible NO synthase (iNOS) in human mesenchymal stem cells in vitro. Furthermore, infection upregulated the expression of the rate-limiting enzyme in the polyamine biosynthetic pathway, ornithine decarboxylase, diverting the iNOS substrate l-arginine toward the synthesis of polyamines. Inhibition of ornithine decarboxylase activity using small interfering RNA or the competitive inhibitor difluoromethylornithine restored iNOS protein expression and activity in infected cells and inhibited chlamydial growth. This inhibition was mediated through tyrosine nitration of chlamydial protein by peroxynitrite, an NO metabolite. Thus, Chlamydia evades innate immunity by inhibiting NO production through induction of the alternative polyamine pathway. PMID- 25114105 TI - The proto-MHC of placozoans, a region specialized in cellular stress and ubiquitination/proteasome pathways. AB - The MHC is a large genetic region controlling Ag processing and recognition by T lymphocytes in vertebrates. Approximately 40% of its genes are implicated in innate or adaptive immunity. A putative proto-MHC exists in the chordate amphioxus and in the fruit fly, indicating that a core MHC region predated the emergence of the adaptive immune system in vertebrates. In this study, we identify a putative proto-MHC with archetypal markers in the most basal branch of Metazoans--the placozoan Trichoplax adhaerens, indicating that the proto-MHC is much older than previously believed--and present in the common ancestor of bilaterians (contains vertebrates) and placozoans. Our evidence for a T. adhaerens proto-MHC was based on macrosynteny and phylogenetic analyses revealing approximately one third of the multiple marker sets within the human MHC-related paralogy groups have unique counterparts in T. adhaerens, consistent with two successive whole genome duplications during early vertebrate evolution. A genetic ontologic analysis of the proto-MHC markers in T. adhaerens was consistent with its involvement in defense, showing proteins implicated in antiviral immunity, stress response, and ubiquitination/proteasome pathway. Proteasome genes psma, psmb, and psmd are present, whereas the typical markers of adaptive immunity, such as MHC class I and II, are absent. Our results suggest that the proto-MHC was involved in intracellular intrinsic immunity and provide insight into the primordial architecture and functional landscape of this region that later in evolution became associated with numerous genes critical for adaptive immunity in vertebrates. PMID- 25114103 TI - Peptidoglycan recognition protein 3 and Nod2 synergistically protect mice from dextran sodium sulfate-induced colitis. AB - Aberrant immune response and changes in the gut microflora are the main causes of inflammatory bowel disease (IBD). Peptidoglycan recognition proteins (Pglyrp1, Pglyrp2, Pglyrp3, and Pglyrp4) are bactericidal innate immunity proteins that maintain normal gut microbiome, protect against experimental colitis, and are associated with IBD in humans. Nucleotide-binding oligomerization domain 2 (Nod2) is an intracellular bacterial sensor and may be required for maintaining normal gut microbiome. Mutations in Nod2 are strongly associated with Crohn's disease, but the causative mechanism is not understood, and the role of Nod2 in ulcerative colitis is not known. Because IBD is likely caused by variable multiple mutations in different individuals, in this study, we examined the combined role of Pglyrp3 and Nod2 in the development of experimental colitis in mice. We demonstrate that a combined deficiency of Pglyrp3 and Nod2 results in higher sensitivity to dextran sodium sulfate-induced colitis compared with a single deficiency. Pglyrp3(-/-)Nod2(-/-) mice had decreased survival and higher loss of body weight, increased intestinal bleeding, higher apoptosis of colonic mucosa, elevated expression of cytokines and chemokines, altered gut microbiome, and increased levels of ATP in the colon. Increased sensitivity to dextran sodium sulfate induced colitis in Pglyrp3(-/-)Nod2(-/-) mice depended on increased apoptosis of intestinal epithelium, changed gut microflora, and elevated ATP. Pglyrp3 deficiency contributed colitis-predisposing intestinal microflora and increased intestinal ATP, whereas Nod2 deficiency contributed higher apoptosis and responsiveness to increased level of ATP. In summary, Pglyrp3 and Nod2 are both required for maintaining gut homeostasis and protection against colitis, but their protective mechanisms differ. PMID- 25114106 TI - 6-Methoxyflavone inhibits NFAT translocation into the nucleus and suppresses T cell activation. AB - NFAT plays a crucial role in the immune system by regulating the transcription of inducible genes during immune responses. In T cells, NFAT proteins govern various cellular events related to T cell development, activation, tolerance induction, and differentiation. We previously reported the NFAT1-dependent enhancer activity of conserved noncoding sequence (CNS)-9, a distal cis-acting element, in the regulation of IL-10 transcription in T cells. In this study, we developed a T cell-based reporter system to identify compounds that modulate the regulatory activity of CNS-9. Among the identified candidates, 6-methoxyflavone (6-MF) significantly inhibited the enhancer activity of CNS-9, thereby reducing IL-10 expression in T cells without affecting cell viability. 6-MF also downregulated the transcription of NFAT1 target genes such as IL-4, IL-13, and IFN-gamma. Treatment of 6-MF inhibited the translocation of NFAT1 into the nucleus, which consequently interrupted NFAT1 binding to the target loci, without affecting the expression or dephosphorylation of NFAT1. Treatment of 6-MF to CD4(+) T cells or B cells isolated from mice with atopic dermatitis significantly reduced disease associated cytokine production, as well as the levels of IgE. In addition, oral administration of 6-MF to atopic dermatitis mice ameliorated disease symptoms by reducing serum IgE levels and infiltrating lymphocytes. Conclusively, our results suggest that 6-MF can be a potential candidate for the development of an effective immunomodulator via the suppression of NFAT-mediated T cell activation. PMID- 25114104 TI - MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite Heligmosomoides polygyrus. AB - Helminth parasites remain one of the most common causes of infections worldwide, yet little is still known about the immune signaling pathways that control their expulsion. C57BL/6 mice are chronically susceptible to infection with the gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we report that C57BL/6 mice lacking the adapter protein MyD88, which mediates signaling by TLRs and IL-1 family members, showed enhanced immunity to H. polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4(+) cells. In addition, MyD88(-/-) mice developed substantial numbers of intestinal granulomas around the site of infection, which were not seen in MyD88-sufficient C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain containing adapter-inducing IFN-beta adapter protein) was also ablated. Mice deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus susceptibility in wild-type mice. To further investigate signaling pathways that are MyD88 dependent, we infected IL-1R1(-/-) mice with H. polygyrus. This genotype displayed heightened granuloma numbers compared with wild-type mice, but without increased parasite expulsion. Thus, the IL-1R-MyD88 pathway is implicated in inhibiting granuloma formation; however, protective immunity in MyD88 deficient mice appears to be granuloma independent. Like IL-1R1(-/-) and MyD88(-/ ) mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1( /-)) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN receptor signaling may provide pathways to impede granuloma formation in vivo, but additional MyD88-mediated signals are associated with inhibition of protective immunity in susceptible C57BL/6 mice. PMID- 25114107 TI - Prevention of neutrophil extravasation by alpha2-adrenoceptor-mediated endothelial stabilization. AB - Adrenergic receptors are expressed on the surface of inflammation-mediating cells, but their potential role in the regulation of the inflammatory response is still poorly understood. The objectives of this work were to study the effects of alpha2-adrenergic agonists on the inflammatory response in vivo and to determine their mechanism of action. In two mouse models of inflammation, zymosan air pouch and thioglycolate-induced peritonitis models, the i.m. treatment with xylazine or UK14304, two alpha2-adrenergic agonists, reduced neutrophil migration by 60%. The alpha2-adrenergic antagonist RX821002 abrogated this effect. In flow cytometry experiments, the basal surface expression of L-selectin and CD11b was modified neither in murine nor in human neutrophils upon alpha2-agonist treatment. Similar experiments in HUVEC showed that UK14304 prevented the activation-dependent upregulation of ICAM-1. In contrast, UK14304 augmented electrical resistance and reduced macromolecular transport through a confluent HUVEC monolayer. In flow chamber experiments, under postcapillary venule-like flow conditions, the pretreatment of HUVECs, but not neutrophils, with alpha2-agonists decreased transendothelial migration, without affecting neutrophil rolling. Interestingly, alpha2-agonists prevented the TNF-alpha-mediated decrease in expression of the adherens junctional molecules, VE-cadherin, beta-catenin, and plakoglobin, and reduced the ICAM-1-mediated phosphorylation of VE-cadherin by immunofluorescence and confocal analysis and Western blot analysis, respectively. These findings indicate that alpha2-adrenoceptors trigger signals that protect the integrity of endothelial adherens junctions during the inflammatory response, thus pointing at the vascular endothelium as a therapeutic target for the management of inflammatory processes in humans. PMID- 25114108 TI - Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen. AB - The yeast phase of Histoplasma capsulatum is the virulent form of this thermally dimorphic fungal pathogen. Among the secreted proteome of Histoplasma, culture filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis. We have generated three monoclonal antibodies as tools for characterization and detection of Cfp4 and determined the epitope each recognizes. Through site directed mutagenesis of Cfp4, we identified three asparagines that function as the principal sites of N-linked glycan modification. To test the function of Cfp4 in Histoplasma pathogenesis, we generated Cfp4-deficient strains by insertional mutagenesis and by RNA interference. Cfp4-deficient strains are not attenuated in virulence in human macrophages or during lung infection in a murine model of histoplasmosis. Coinfection of differentially marked Cfp4-producing and Cfp4 deficient strains demonstrates that production of Cfp4 does not confer a fitness advantage to Histoplasma yeasts during murine lung infection. Despite no apparent role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast cells is consistent across clinical and laboratory isolates of the North American type 1 and type 2 phylogenetic groups as well as a strain from Panama. In addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming Cfp4 production during infection of human hosts. These results suggest the potential utility of Cfp4 as a diagnostic exoantigen for histoplasmosis. PMID- 25114111 TI - Tick passage results in enhanced attenuation of Babesia bovis. AB - Serial blood passage of virulent Babesia bovis in splenectomized cattle results in attenuated derivatives that do not cause neurologic disease. Tick transmissibility can be lost with attenuation, but when retained, attenuated B. bovis can revert to virulence following tick passage. This study provides data showing that tick passage of the partially attenuated B. bovis T2Bo derivative strain further decreased virulence compared with intravenous inoculation of the same strain in infected animals. Ticks that acquired virulent or attenuated parasites by feeding on infected cattle were transmission fed on naive, splenectomized animals. While there was no significant difference between groups in the number of parasites in the midgut, hemolymph, or eggs of replete female ticks after acquisition feeding, animals infected with the attenuated parasites after tick transmission showed no clinical signs of babesiosis, unlike those receiving intravenous challenge with the same attenuated strain prior to tick passage. Additionally, there were significantly fewer parasites in blood and tissues of animals infected with tick-passaged attenuated parasites. Sequencing analysis of select B. bovis genes before and after tick passage showed significant differences in parasite genotypes in both peripheral blood and cerebral samples. These results provide evidence that not only is tick transmissibility retained by the attenuated T2Bo strain, but also it results in enhanced attenuation and is accompanied by expansion of parasite subpopulations during tick passage that may be associated with the change in disease phenotype. PMID- 25114110 TI - Masking of beta(1-3)-glucan in the cell wall of Candida albicans from detection by innate immune cells depends on phosphatidylserine. AB - The virulence of Candida albicans in a mouse model of invasive candidiasis is dependent on the phospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE). Disruption of the PS synthase gene CHO1 (i.e., cho1Delta/Delta) eliminates PS and blocks the de novo pathway for PE biosynthesis. In addition, the cho1Delta/Delta mutant's ability to cause invasive disease is severely compromised. The cho1Delta/Delta mutant also exhibits cell wall defects, and in this study, it was determined that loss of PS results in decreased masking of cell wall beta(1-3)-glucan from the immune system. In wild type C. albicans, the outer mannan layer of the wall masks the inner layer of beta(1-3)-glucan from exposure and detection by innate immune effector molecules like the C-type signaling lectin Dectin-1, which is found on macrophages, neutrophils, and dendritic cells. The cho1Delta/Delta mutant exhibits increases in exposure of beta(1-3)-glucan, which leads to greater binding by Dectin-1 in both yeast and hyphal forms. The unmasking of beta(1-3)-glucan also results in increased elicitation of TNF-alpha from macrophages in a Dectin-1-dependent manner. The role of phospholipids in fungal pathogenesis is an emerging field, and this is the first study showing that loss of PS in C. albicans results in decreased masking of beta(1-3)-glucan, which may contribute to our understanding of fungus-host interactions. PMID- 25114109 TI - LcrV delivered via type III secretion system of live attenuated Yersinia pseudotuberculosis enhances immunogenicity against pneumonic plague. AB - Here, we constructed a Yersinia pseudotuberculosis mutant strain with arabinose dependent regulated and delayed shutoff of crp expression (araC P(BAD) crp) and replacement of the msbB gene with the Escherichia coli msbB gene to attenuate it. Then, we inserted the asd mutation into this construction to form chi10057 [Deltaasd-206 DeltamsbB868::P(msbB) msbB(EC) DeltaP(crp21)::TT araC P(BAD) crp] for use with a balanced-lethal Asd-positive (Asd(+)) plasmid to facilitate antigen synthesis. A hybrid protein composed of YopE (amino acids [aa]1 to 138) fused with full-length LcrV (YopE(Nt138)-LcrV) was synthesized in chi10057 harboring an Asd(+) plasmid (pYA5199, yopE(Nt138)-lcrV) and could be secreted through a type III secretion system (T3SS) in vitro and in vivo. Animal studies indicated that mice orally immunized with chi10057(pYA5199) developed titers of IgG response to whole-cell lysates of Y. pestis (YpL) and subunit LcrV similar to those seen with chi10057(pYA3332) (chi10057 plus an empty plasmid). However, only immunization of mice with chi10057(pYA5199) resulted in a significant secretory IgA response to LcrV. chi10057(pYA5199) induced a higher level of protection (80% survival) against intranasal (i.n.) challenge with ~240 median lethal doses (LD50) (2.4 * 10(4) CFU) of Y. pestis KIM6+(pCD1Ap) than chi10057(pYA3332) (40% survival). Splenocytes from mice vaccinated with chi10057(pYA5199) produced significant levels of gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-17 (IL-17) after restimulation with LcrV and YpL antigens. Our results suggest that it is possible to use an attenuated Y. pseudotuberculosis strain delivering the LcrV antigen via the T3SS as a potential vaccine candidate against pneumonic plague. PMID- 25114112 TI - The serine/threonine kinase STK11 promotes Shigella flexneri dissemination through establishment of cell-cell contacts competent for tyrosine kinase signaling. AB - Shigella flexneri is an intracellular pathogen that disseminates in the intestinal epithelium by displaying actin-based motility. We found that although S. flexneri displayed comparable actin-based motilities in the cytosols of HeLa229 and HT-29 epithelial cell lines, the overall dissemination process was much more efficient in HT-29 cells. Time-lapse microscopy demonstrated that as motile bacteria reached the cell cortex in HT-29 cells, they formed membrane protrusions that resolved into vacuoles, from which the bacteria escaped and gained access to the cytosol of adjacent cells. In HeLa229 cells, S. flexneri also formed membrane protrusions that extended into adjacent cells, but the protrusions rarely resolved into vacuoles. Instead, the formed protrusions collapsed and retracted, bringing the bacteria back to the cytosol of the primary infected cells. Silencing the serine/threonine kinase STK11 (also known as LKB1) in HT-29 cells decreased the efficiency of protrusion resolution into vacuoles. Conversely, expressing STK11 in HeLa229 cells, which lack the STK11 locus, dramatically increased the efficiency of protrusion resolution into vacuoles. S. flexneri dissemination in HT-29 cells led to the local phosphorylation of tyrosine residues in protrusions, a signaling event that was not observed in HeLa229 cells but was restored in STK11-expressing HeLa229 cells. Treatment of HT 29 cells with the tyrosine kinase inhibitor imatinib abrogated tyrosine kinase signaling in protrusions, which correlated with a severe decrease in the efficiency of protrusion resolution into vacuoles. We suggest that the formation of STK11-dependent lateral cell-cell contacts competent for tyrosine kinase signaling promotes S. flexneri dissemination in epithelial cells. PMID- 25114113 TI - Epithelial innate immune response to Acinetobacter baumannii challenge. AB - Currently, Acinetobacter baumannii is recognized as one of the major pathogens seriously threatening our health care delivery system. Aspects of the innate immune response to A. baumannii infection are not yet well understood. Human beta defensins (hBDs) are epithelial cell-derived cationic antimicrobial peptides (AMPs) that also function to bridge the innate and adaptive immune system. We tested the induction of hBD-2 and -3 by A. baumannii on primary oral and skin epithelial cells and found that A. baumannii induces hBD-3 transcripts to a greater extent than it induces hBD-2 transcripts on both types of cells. In addition, we found that A. baumannii is susceptible to hBD-2 and -3 killing at submicromolar concentrations. Moreover, hBD-3 induction by A. baumannii was found to be dependent on epidermal growth factor receptor (EGFR) signaling. Inhibition of mitogen-activated protein kinase resulted in reduced expression of both hBD-2 and -3. Lastly, a disintegrin and metalloprotease 17 (ADAM17; also known as TACE) was found to be critical for hBD-3 induction, while ADAM10 and dual oxidase 1 (Duox1) were not required for hBD-3 induction. Induction of AMPs is an important component of innate sensing of pathogens and may play an important role in triggering systemic immune responses to A. baumannii infection. Further studies on the interactions between epithelial cells and A. baumannii will help us understand early stages of infection and may shed light on why some individuals are more vulnerable to A. baumannii infection. PMID- 25114114 TI - BDCA1-positive dendritic cells (DCs) represent a unique human myeloid DC subset that induces innate and adaptive immune responses to Staphylococcus aureus Infection. AB - Staphylococcus aureus bloodstream infection (bacteremia) is a major cause of morbidity and mortality and places substantial cost burdens on health care systems. The role of peripheral blood dendritic cells (PBDCs) in the immune responses against S. aureus infection has not been well characterized. In this study, we demonstrated that BDCA1(+) myeloid DCs (mDCs) represent a unique PBDC subset that can induce immune responses against S. aureus infection. BDCA1(+) mDCs could engulf S. aureus and strongly upregulated the expression of costimulatory molecules and production of proinflammatory cytokines. Furthermore, BDCA1(+) mDCs expressed high levels of major histocompatibility complex (MHC) class I and II molecules in response to S. aureus and greatly promoted proliferation and gamma interferon (IFN-gamma) production in CD4 and CD8 T cells. Moreover, BDCA1(+) mDCs expressed higher levels of Toll-like receptor 2 (TLR-2) and scavenger receptor A (SR-A) than those on CD16(+) and BDCA3(+) mDCs, and these two receptors were both required for the recognition of S. aureus and the subsequent activation of BDCA1(+) mDCs. Finally, BDCA1(+) mDC-mediated immune responses against S. aureus were dependent on MyD88 signaling pathways. These results demonstrate that human BDCA1(+) mDCs represent a unique subset of mDCs that can respond to S. aureus to undergo maturation and activation and to induce Th1 and Tc1 immune responses. PMID- 25114116 TI - Blockade of indoleamine 2,3-dioxygenase reduces mortality from peritonitis and sepsis in mice by regulating functions of CD11b+ peritoneal cells. AB - Indoleamine 2,3-dioxygenase-1 (Ido), which catalyzes the first and limiting step of tryptophan catabolism, has been implicated in immune tolerance. However, the roles of Ido in systemic bacterial infection are complicated and remain controversial. To explore this issue, we examined the roles of Ido in bacterial peritonitis and sepsis after cecal ligation and puncture (CLP) in mice by using the Ido inhibitor 1-methyl-d,l-tryptophan (1-MT), by comparing Ido(+/+) and Ido( /-) mice, or by using chimeric mice in which Ido in the bone marrow-derived cells was deficient. Ido expression in the peritoneal CD11b(+) cells and its metabolite l-kynurenine in the serum were increased after CLP. 1-MT treatment or Ido deficiency, especially in bone marrow-derived cells, reduced mortality after CLP. Compared to Ido(+/+) mice, Ido(-/-) mice showed increased recruitment of neutrophils and mononuclear cells into the peritoneal cavity and a decreased bacterial count in the blood accompanied by increased CXCL-2 and CXCL-1 mRNA in the peritoneal cells. Ido has an inhibitory effect on LPS-induced CXCL-2 and CXCL 1 production in cultured peritoneal cells. These findings indicate that inhibition of Ido reduces mortality from peritonitis and sepsis after CLP via recruitment of neutrophils and mononuclear cells by chemokine production in peritoneal CD11b(+) cells. Thus, blockade of Ido plays a beneficial role in host protection during bacterial peritonitis and sepsis. PMID- 25114115 TI - New insights into the antimicrobial effect of mast cells against Enterococcus faecalis. AB - Enterococcus faecalis has emerged as an important cause of life-threatening multidrug-resistant bacterial infections in the hospital setting. The pathogenesis of enterococcal infections has remained a relatively neglected field despite their obvious clinical relevance. The objective of this study was to characterize the interactions between mast cells (MCs), an innate immune cell population abundant in the intestinal lamina propria, and E. faecalis. This study was conducted with primary bone marrow-derived murine MCs. The results demonstrated that MCs exerted an antimicrobial effect against E. faecalis that was mediated both by degranulation, with the concomitant discharge of the antimicrobial effectors contained in the granules, and by the release of extracellular traps, in which E. faecalis was snared and killed. In particular, the cathelicidin LL-37 released by the MCs had potent antimicrobial effect against E. faecalis. We also investigated the specific receptors involved in the recognition of E. faecalis by MCs. We found that Toll-like receptors (TLRs) are critically involved in the MC recognition of E. faecalis, since MCs deficient in the expression of MyD88, an adaptor molecule required for signaling by most TLRs, were significantly impaired in their capacity to degranulate, to reduce E. faecalis growth as well as to release tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) after encountering this pathogen. Furthermore, TLR2 was identified as the most prominent TLR involved in the recognition of E. faecalis by MCs. The results of this study indicate that MCs may be important contributors to the host innate immune defenses against E. faecalis. PMID- 25114117 TI - The interleukin-1beta/CXCL1/2/neutrophil axis mediates host protection against group B streptococcal infection. AB - Previous studies have indicated that group B streptococcus (GBS), a frequent human pathogen, potently induces the release of interleukin-1beta (IL-1beta), an important mediator of inflammatory responses. Since little is known about the role of this cytokine in GBS disease, we analyzed the outcome of infection in IL 1beta-deficient mice. These animals were markedly sensitive to GBS infection, with most of them dying under challenge conditions that caused no deaths in wild type control mice. Lethality was due to the inability of the IL-1beta-deficient mice to control local GBS replication and dissemination to target organs, such as the brain and the kidneys. Moreover, in a model of inflammation induced by the intraperitoneal injection of killed GBS, a lack of IL-1beta was associated with selective impairment in the production of the neutrophil chemokines CXCL1 and CXCL2 and in neutrophil recruitment to the peritoneal cavity. Decreased blood neutrophil counts and impaired neutrophil recruitment to the brain and kidneys were also observed during GBS infection in IL-1beta-deficient mice concomitantly with a reduction in CXCL1 and CXCL2 tissue levels. Notably, the hypersusceptibility to GBS infection observed in the immune-deficient animals was recapitulated by neutrophil depletion with anti-Gr1 antibodies. Collectively, our data identify a cytokine circuit that involves IL-1beta-induced production of CXCL1 and CXCL2 and leads the recruitment of neutrophils to GBS infection sites. Moreover, our data point to an essential role of these cells in controlling the progression and outcome of GBS disease. PMID- 25114119 TI - Characterization of a lipopolysaccharide-targeted monoclonal antibody and its variable fragments as candidates for prophylaxis against the obligate intracellular bacterial pathogen Coxiella burnetii. AB - Our previous study demonstrated that treatment of Coxiella burnetii with the phase I lipopolysaccharide (PI-LPS)-targeted monoclonal antibody (MAb) 1E4 significantly inhibited C. burnetii infection in mice, suggesting that 1E4 is a protective MAb. To determine whether passive transfer of antibodies (Abs) can provide protection against C. burnetii natural infection, we examined if passive transfer of 1E4 would protect SCID mice against C. burnetii aerosol infection. The results indicated that 1E4 conferred significant protection against aerosolized C. burnetii, suggesting that 1E4 may be useful for preventing C. burnetii natural infection. To further understand the mechanisms of 1E4-mediated protection and to test the possibility of using humanized 1E4 to prevent C. burnetii infection, we examined whether the Fab fragment of 1E4 (Fab1E4), a recombinant murine single-chain variable fragment (muscFv1E4), and a humanized single-chain variable fragment (huscFv1E4) retained the ability of 1E4 to inhibit C. burnetii infection. The results indicated that Fab1E4, muscFv1E4, and huscFv1E4 were able to inhibit C. burnetii infection in mice but that their ability to inhibit C. burnetii infection was lower than that of 1E4. In addition, treatment of C. burnetii with Fab1E4, muscFv1E4, or huscFv1E4 can block C. burnetii infection of macrophages. Interestingly, treatment of C. burnetii with huscFv1E4 can significantly reduce C. burnetii infectivity in human macrophages. This report provides the first evidence to demonstrate that the humanized variable fragments of an LPS-specific MAb can neutralize C. burnetii infection and appears to be a promising step toward the potential use of a humanized MAb as emergency prophylaxis against C. burnetii exposure. PMID- 25114121 TI - Human monocyte subsets at homeostasis and their perturbation in numbers and function in filarial infection. AB - To characterize the function and plasticity of the major human circulating monocyte populations and to explore their role in systemic helminth infection, highly purified (by flow-based sorting) human monocyte subsets (CD14(hi)/CD16(neg) [classical], CD14(+ or hi)/CD16(med) [intermediate], and CD14(neg)/CD16(hi) [nonclassical]) were examined at homeostasis and after activation. Among these three subsets the classical and intermediate subsets were found to be the major sources of inflammatory and regulatory cytokines, as well as cytokines/chemokines associated with alternative activation, whereas the nonclassical and classical populations demonstrated an ability to transmigrate through endothelial monolayers. Moreover, it was primarily the classical subset that was the most efficient in promoting autologous T cell proliferation. The distribution of these subsets changed in the context of a systemic helminth (Wuchereria bancrofti) infection such that patent infection altered the frequency and distribution of these monocyte subsets with the nonclassical monocytes being expanded (almost 2-fold) in filarial infection. To understand further the filarial/monocyte interface, in vitro modeling demonstrated that the classical subset internalized filarial antigens more efficiently than the other two subsets but that the parasite-driven regulatory cytokine interleukin-10 was exclusively coming from the intermediate subset. Our data suggest that monocyte subsets have a differential function at homeostasis and in response to helminth parasites. PMID- 25114118 TI - Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. AB - Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also observed in vitro, where this limitation was alleviated in the presence of the alternative electron acceptor nitrate. The finding that P. aeruginosa growth patterns correlate with the number of surrounding PMNs points to a bacteriostatic effect by PMNs via their strong O2 consumption, which slows the growth of P. aeruginosa in infected CF lungs. In support of this, the growth of P. aeruginosa was significantly higher in the respiratory airways than in the conducting airways of mice. These results indicate a complex host-pathogen interaction in chronic P. aeruginosa infection of the CF lung whereby PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration. PMID- 25114120 TI - Bacterial heterogeneity is a requirement for host superinfection by the Lyme disease spirochete. AB - In nature, mixed Borrelia burgdorferi infections are common and possibly can be acquired by either superinfection or coinfection. Superinfection by heterologous B. burgdorferi strains has been established experimentally, although the ability of homologous B. burgdorferi clones to superinfect a host has not been studied in detail. Information regarding any potential immune barriers to secondary infection also currently is unavailable. In the present study, the ability to superinfect various mouse models by homologous wild-type clones was examined and compared to superinfection by heterologous strains. To assess the ability of homologous B. burgdorferi clones to successfully superinfect a mouse host, primary- and secondary-infecting spirochetes were recovered via in vitro cultivation of collected blood or tissue samples. This was accomplished by generating two different antibiotic-resistant versions of the wild-type B31-A3 clone in order to distinguish superinfecting B. burgdorferi from primary infecting spirochetes. The data demonstrate an inability of homologous B. burgdorferi to superinfect immunocompetent mice as opposed to heterologous strains. Attempts to superinfect different types of immunodeficient mice with homologous B. burgdorferi indicate that the murine innate immune system represents a major barrier to intrastrain superinfection. Consequently, the possibility of innate immunity as a driving force for B. burgdorferi heterogeneity during the enzootic cycle is discussed. PMID- 25114123 TI - Fixed versus removable orthodontic appliances to correct anterior crossbite in the mixed dentition--a randomized controlled trial. AB - OBJECTIVE: To compare the effectiveness of fixed and removable orthodontic appliances in correcting anterior crossbite with functional shift in the mixed dentition. SUBJECTS AND METHODS: Consecutive recruitment of 64 patients who met the following inclusion criteria: early to late mixed dentition, anterior crossbite with functional shift, moderate space deficiency in the maxilla, i.e. up to 4mm, a non-extraction treatment plan, the ANB angle > 0 degree, and no previous orthodontic treatment. Sixty-two patients agreed to participate. The study was designed as a randomized controlled trial with two parallel arms. After written consent was obtained, the patients were randomized, in blocks of 10, for treatment either with a removable appliance with protruding springs or a fixed appliance with multi-brackets. The main outcome measures assessed were success rate, duration of treatment, and changes in overjet, overbite, and arch length. The results were also analysed on an intention-to-treat basis. RESULTS: The crossbite was successfully corrected in all patients in the fixed appliance group and all except one in the removable appliance group. The average duration of treatment was significantly less, 1.4 months, for the fixed appliance group (P < 0.05). There were significant increases in arch length and overjet in both treatment groups, but significantly more in the fixed appliance group (P < 0.05 and P < 0.01). CONCLUSION: Anterior crossbite with functional shift in the mixed dentition can be successfully corrected by either fixed or removable appliance therapy in a short-term perspective. PMID- 25114124 TI - Alveolar bone mapping in subjects with different vertical facial dimensions. AB - OBJECTIVE: The purpose of this study was to investigate differences in alveolar and skeletal dimensions among subjects with different vertical facial dimensions using cone beam computed tomography (CBCT). To date, this is the first study that investigates the relationship between facial type and posterior alveolar thickness in both maxilla and mandible, using CBCT data. MATERIALS AND METHODS: From a sample of 152 CBCT scans, 45 scans were selected to be included in the study. CBCT-synthesized lateral cephalograms were used to categorize subjects into three groups based on their vertical skeletal pattern. Using iCATVisionTM software, measurements of alveolar height and thickness were carried out in the entire tooth-bearing region. In addition, AutoCADTM software was used to carry out measurements for the anatomical limitation to labio-lingual incisor movement. Kruskal-Wallis and Mann-Whitney U-tests with the Bonferroni adjustment were done for statistical analyses. RESULTS: Compared to the other two groups, high-angle group had larger anterior dentoalveolar height with no significant differences in alveolar height posteriorly, in both the maxilla and mandible. Furthermore, high angle group presented thinner alveolus anteriorly in the maxilla and at almost all sites in the mandible. Low-angle group had higher mean values for some measurements of the anatomical limitation to labio-lingual incisor movement for all upper and lower incisors. LIMITATIONS: Inherent limitations of CBCT scanning as related to physical spatial resolution of the image and limitations posed by the study sample size should be considered. CONCLUSIONS: There is a statistically significant relationship between facial type and alveolar height and thickness. High-angle subjects can be at increased risk of moving incisors beyond alveolar bone support when subjected to marked antero-posterior incisor movement. PMID- 25114122 TI - Role of pathogen-derived cell wall carbohydrates and prostaglandin E2 in immune response and suppression of fish immunity by the oomycete Saprolegnia parasitica. AB - Saprolegnia parasitica is a freshwater oomycete that is capable of infecting several species of fin fish. Saprolegniosis, the disease caused by this microbe, has a substantial impact on Atlantic salmon aquaculture. No sustainable treatment against saprolegniosis is available, and little is known regarding the host response. In this study, we examined the immune response of Atlantic salmon to S. parasitica infection and to its cell wall carbohydrates. Saprolegnia triggers a strong inflammatory response in its host (i.e., induction of interleukin-1beta1 [IL-1beta1], IL-6, and tumor necrosis factor alpha), while severely suppressing the expression of genes associated with adaptive immunity in fish, through downregulation of T-helper cell cytokines, antigen presentation machinery, and immunoglobulins. Oomycete cell wall carbohydrates were recognized by fish leukocytes, triggering upregulation of genes involved in the inflammatory response, similar to what is observed during infection. Our data suggest that S. parasitica is capable of producing prostaglandin [corrected] E2 (PGE2) in vitro, a metabolite not previously shown to be produced by oomycetes, and two proteins with homology to vertebrate enzymes known to play a role in prostaglandin biosynthesis have been identified in the oomycete genome. Exogenous PGE2 was shown to increase the inflammatory response in fish leukocytes incubated with cell wall carbohydrates while suppressing genes involved in cellular immunity (gamma interferon [IFN-gamma] and the IFN-gamma-inducible protein [gamma-IP]). Inhibition of S. parasitica zoospore germination and mycelial growth by two cyclooxygenase inhibitors (aspirin and indomethacin) also suggests that prostaglandins may be involved in oomycete development. PMID- 25114125 TI - Does coronary endarterectomy technique affect surgical outcome when combined with coronary artery bypass grafting? AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether open coronary endarterectomy (CE) and coronary artery bypass grafting (CABG) compares favourably with closed endarterectomy and CABG in the myocardial revascularization of patients presenting with diffuse coronary artery disease (DCAD). One hundred and fifty five articles were identified by a systematic search, of which 10 best answered the clinical question incorporating a total of 1203 patients (915 open-CE, 288 closed-CE). All were observational studies. Two were comparative and the remaining eight were case series. The authors, journal, date, country of publication, patient group, study type, relevant outcomes and results were recorded. The open technique involved removal of atheroma under direct vision through an arteriotomy along the length of diffusely stenotic artery, whereas the closed technique involved a smaller arteriotomy and removal via traction on the proximal plaque. The overall postoperative mortality rate associated with open-CE ranged from 2.3 to 10.5%. Both comparative studies demonstrated at least equivalent 30-day mortality between open-CE and closed-CE. Notably, the four studies with highest overall postoperative mortality used a saphenous vein (SV) graft in the majority of patients. Furthermore, two-vessel CE was associated with higher mortality rates. Among these best evidence series, the overall incidence rate of postoperative myocardial infarction (MI) was 7.3% (88/1203). Whether open CE or the use of internal thoracic artery (ITA) conduit over SV affects postoperative MI rates remains inconclusive. Mid-term and long-term graft patency, and 3-, 4- and 5-year survival rates are all improved when open-CE is combined with the ITA bypass conduit, when compared with closed-CE or open-CE using another conduit. In summary, open-CE with CABG in the setting of DCAD may carry lower 30-day mortality than closed-CE with CABG. Utilization of ITA appears to improve mortality, whereas the SV conduit and multivessel CE may worsen clinical outcome. Furthermore, the ITA may also improve graft patency when combined with open-CE. There is currently insufficient evidence to determine the effect of open-CE on MI incidence. Future large, prospective studies are now required with defined subgroups, stratifying technique, number and territory of the endarterectomy and conduit type in order to determine the patients in whom open-CE may confer the greatest benefit. PMID- 25114126 TI - Identification of Acinetobacter baumannii serum-associated antibiotic efflux pump inhibitors. AB - Adaptive antibiotic resistance is a newly described phenomenon by which Acinetobacter baumannii induces efflux pump activity in response to host associated environmental cues that may, in part, account for antibiotic treatment failures against clinically defined susceptible strains. To that end, during adaptation to growth in human serum, the organism induces approximately 22 putative efflux-associated genes and displays efflux-mediated minocycline tolerance at antibiotic concentrations corresponding to patient serum levels. Here, we show that in addition to minocycline, growth in human serum elicits A. baumannii efflux-mediated tolerance to the antibiotics ciprofloxacin, meropenem, tetracycline, and tigecycline. Moreover, using a whole-cell high-throughput screen and secondary assays, we identified novel serum-associated antibiotic efflux inhibitors that potentiated the activities of antibiotics toward serum grown A. baumannii. Two compounds, Acinetobacter baumannii efflux pump inhibitor 1 (ABEPI1) [(E)-4-((4-chlorobenzylidene)amino)benezenesulfonamide] and ABEPI2 [N tert-butyl-2-(1-tert-butyltetrazol-5-yl)sulfanylacetamide], were shown to lead to minocycline accumulation within A. baumannii during serum growth and inhibit the efflux potential of the organism. While both compounds also inhibited the antibiotic efflux properties of the bacterial pathogen Pseudomonas aeruginosa, they did not display significant cytotoxicity toward human cells or mammalian Ca(2+) channel inhibitory effects, suggesting that ABEPI1 and ABEPI2 represent promising structural scaffolds for the development of new classes of bacterial antibiotic efflux pump inhibitors that can be used to potentiate the activities of current and future antibiotics for the therapeutic intervention of Gram negative bacterial infections. PMID- 25114127 TI - A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel antimalarial Spiroindolone KAE609 (Cipargamin) to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers. AB - This first-in-human randomized, double-blind, placebo-controlled, ascending single and -multiple oral dose study was designed to evaluate the safety, tolerability, and pharmacokinetics in healthy volunteers of KAE609 (cipargamin; formerly NITD609), a spiroindolone now in trials for malaria treatment. It was studied in single-dose cohorts (1 to 300 mg, including one 30-mg food effect cohort) with 4 to 10 subjects in each cohort and in multiple-dose cohorts (10 to 150 mg once daily for 3 days) with 8 subjects in each cohort. The follow-up period was 6 to 8 days post-last dose. Safety and pharmacokinetics were assessed at scheduled time points during the study. Systemic exposure in terms of the area under the concentration-time curve from 0 h extrapolated to infinity (AUC0 infinity) increased in a dose-proportional manner over the dose range of 1 to 300 mg. The AUC from time zero to the time of the last quantifiable concentration (AUClast) and the maximum concentration of drug in plasma (Cmax) also increased in an approximately dose-proportional manner. When administered daily for 3 days, the accumulation ratio on day 3 (the AUC from time zero to 24 h postdosing [AUC0 24] on day 3/AUC0-24 on day 1) was in the range of 1.5 to 2 in the studied dose range (10 to 150 mg) and was consistent with an elimination half-life of around 24 h. Urine analysis for unchanged KAE609 revealed negligible amounts (<=0.01%) were excreted renally. The high fat food intake did not affect the extent of KAE609 absorption (AUC); however, the Cmax was reduced by around 27%. KAE609 was tolerated in this study, with transient gastrointestinal and genitourinary adverse events of mild to moderate intensity (semen discoloration, diarrhea, nausea and abdominal discomfort, dizziness and headache, catheter site hematoma). Gastrointestinal and genitourinary adverse events increased with rising doses. PMID- 25114128 TI - Ascorbate peroxidase, a key molecule regulating amphotericin B resistance in clinical isolates of Leishmania donovani. AB - Amphotericin B (AmB), a polyene macrolide, is now a first-line treatment of visceral leishmaniasis cases refractory to antimonials in India. AmB relapse cases and the emergence of secondary resistance have now been reported. To understand the mechanism of AmB, differentially expressed genes in AmB resistance strains were identified by a DNA microarray and real-time reverse transcriptase PCR (RT-PCR) approach. Of the many genes functionally overexpressed in the presence of AmB, the ascorbate peroxidase gene from a resistant Leishmania donovani strain (LdAPx gene) was selected because the gene is present only in Leishmania, not in humans. Apoptosis-like cell death after exposure to AmB was investigated in a wild-type (WT) strain in which the LdAPx gene was overexpressed and in AmB-sensitive and -resistant strains. A higher percentage of apoptosis like cell death after AmB treatment was noticed in the sensitive strain than in both the resistant isolate and the strain sensitive to LdAPx overexpression. This event is preceded by AmB-induced formation of reactive oxygen species and elevation of the cytosolic calcium level. Enhanced cytosolic calcium was found to be responsible for depolarization of the mitochondrial membrane potential and the release of cytochrome c (Cyt c) into the cytosol. The redox behavior of Cyt c showed that it has a role in the regulation of apoptosis-like cell death by activating metacaspase- and caspase-like proteins and causing concomitant nuclear alterations, as determined by terminal deoxynucleotidyltransferase-mediated dUTP biotin nick end labeling (TUNEL) and DNA fragmentation in the resistant strain. The present study suggests that constitutive overexpression of LdAPx in the L. donovani AmB-resistant strain prevents cells from the deleterious effect of oxidative stress, i.e., mitochondrial dysfunction and cellular death induced by AmB. PMID- 25114129 TI - Resveratrol is active against Leishmania amazonensis: in vitro effect of its association with Amphotericin B. AB - Resveratrol is a polyphenol found in black grapes and red wine and has many biological activities. In this study, we evaluated the effect of resveratrol alone and in association with amphotericin B (AMB) against Leishmania amazonensis. Our results demonstrate that resveratrol possesses both antipromastigote and antiamastigote effects, with 50% inhibitory concentrations (IC50s) of 27 and 42 MUM, respectively. The association of resveratrol with AMB showed synergy for L. amazonensis amastigotes, as demonstrated by the mean sums of fractional inhibitory index concentration (mean SigmaFIC) of 0.483, although for promastigotes, this association was indifferent. Treatment with resveratrol increased the percentage of promastigotes in the sub-G0/G1 phase of the cell cycle, reduced the mitochondrial potential, and showed an elevated choline peak and CH2-to-CH3 ratio in the nuclear magnetic resonance (NMR) spectroscopy analysis; all these features indicate parasite death. Resveratrol also decreased the activity of the enzyme arginase in uninfected and infected macrophages with and without stimulation with interleukin-4 (IL-4), also implicating arginase inhibition in parasite death. The anti-Leishmania effect of resveratrol and its potential synergistic association with AMB indicate that these compounds should be subjected to further studies of drug association therapy in vivo. PMID- 25114130 TI - Combination of the CCL5-derived peptide R4.0 with different HIV-1 blockers reveals wide target compatibility and synergic cobinding to CCR5. AB - R4.0, a synthetic CCL5/RANTES-derived peptide, exerts potent anti-HIV-1 activity via its nonactivating interaction with CCR5, the major HIV-1 coreceptor. CCR5 chronic activation may promote undesirable inflammatory effects and enhance viral infection; thus, receptor antagonism is a necessary requisite. HIV-1 gp120, CCL5, and maraviroc dock on CCR5 by sharing two receptor sites: the N terminus and the second extracellular loop. In combination studies, R4.0, CCL5, and maraviroc exhibited concomitant interactions with CCR5 and promoted synergic inhibition of HIV-1 in acute-infection assays. Furthermore, various degrees of additive/synergic HIV-1 inhibition were observed when R4.0 was tested in combination with drugs and lead compounds directed toward different viral targets (gp120, gp41, reverse transcriptase, and protease). In combination with tenofovir, R4.0 provides cross-clade synergic inhibition of primary HIV-1 isolates. Remarkably, an in vitro-generated maraviroc-resistant R5 HIV-1 strain was inhibited by R4.0 comparably to the wild-type strain, suggesting the presence of viral resistance barriers similar to those reported for CCL5. Overall, R4.0 appears to be a promising lead peptide with potential for combination in anti-HIV 1 therapy and in microbicide development to prevent sexual HIV-1 transmission. PMID- 25114131 TI - Chloroquine has a cytotoxic effect on Acanthamoeba encystation through modulation of autophagy. AB - Encystation of Acanthamoeba castellanii is associated with resistance to chemotherapeutic agents. Blocking the encystation process could potentiate the efficacy of chemotherapeutic agents and biocides. During encystation, autophagy is highly stimulated and required for proper encystation of Acanthamoeba. In this study, the cytotoxic effect of chloroquine, a well-known autophagy-inhibitory drug, was tested in A. castellanii. Chloroquine was able to selectively reduce cell survival during the encystation of A. castellanii. However, A. castellanii trophozoites and mature cysts were resistant to chloroquine. Chloroquine treatment led to an increase in the number and size of lysosomes in encysting cells. Moreover, chloroquine inhibited the degradation of long-lived proteins in the encysting cells. Decreased autophagic flux, indicated by an increased number of lysosomes and decreased degradation of long-lived proteins, may be the mechanism by which cell death is induced by chloroquine in encysting Acanthamoeba. These results suggest a potential novel therapeutic application of chloroquine as an anti-Acanthamoeba drug. Our findings also suggest that targeting autophagy could be a therapeutic strategy against Acanthamoeba infection. PMID- 25114132 TI - Pharmacokinetics of para-aminosalicylic acid in HIV-uninfected and HIV-coinfected tuberculosis patients receiving antiretroviral therapy, managed for multidrug resistant and extensively drug-resistant tuberculosis. AB - The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis prompted the reintroduction of para-aminosalicylic acid (PAS) to protect companion anti-tuberculosis drugs from additional acquired resistance. In sub-Saharan Africa, MDR/XDR tuberculosis with HIV coinfection is common, and concurrent treatment of HIV infection and MDR/XDR tuberculosis is required. Out of necessity, patients receive multiple drugs, and PAS therapy is frequent; however, neither potential drug interactions nor the effects of HIV infection are known. Potential drug-drug interaction with PAS and the effect of HIV infection was examined in 73 pulmonary tuberculosis patients; 22 (30.1%) were HIV coinfected. Forty-one pulmonary MDR or XDR tuberculosis patients received 4 g PAS twice daily, and in a second crossover study, another 32 patients were randomized, receiving 4 g PAS twice daily or 8 g PAS once daily. A PAS population pharmacokinetic model in two dosing regimens was developed; potential covariates affecting its pharmacokinetics were examined, and Monte Carlo simulations were conducted evaluating the pharmacokinetic-pharmacodynamic index. The probability of target attainment (PTA) to maintain PAS levels above MIC during the dosing interval was estimated by simulation of once-, twice-, and thrice-daily dosing regimens not exceeding 12 g daily. Concurrent efavirenz (EFV) medication resulted in a 52% increase in PAS clearance and a corresponding >30% reduction in mean PAS area under the concentration curve in 19 of 22 HIV-M. tuberculosis-coinfected patients. Current practice recommends maintenance of PAS concentrations at >=1 MUg/ml (the MIC of M. tuberculosis), but the model predicts that at only a minimum dose of 4 g twice daily can this PTA be achieved in at least 90% of the population, whether or not EFV is concomitantly administered. Once-daily dosing of 12 g PAS will not provide PAS concentrations exceeding the MIC over the entire dosing interval if coadministered with EFV, while 4 g twice daily ensures concentrations exceeding MIC over the entire dosing interval, even in HIV infected patients who received EFV. PMID- 25114133 TI - Molecular mechanism of MBX2319 inhibition of Escherichia coli AcrB multidrug efflux pump and comparison with other inhibitors. AB - Efflux pumps of the resistance nodulation division (RND) superfamily, such as AcrB, make a major contribution to multidrug resistance in Gram-negative bacteria. The development of inhibitors of the RND pumps would improve the efficacy of current and next-generation antibiotics. To date, however, only one inhibitor has been cocrystallized with AcrB. Thus, in silico structure-based analysis is essential for elucidating the interaction between other inhibitors and the efflux pumps. In this work, we used computer docking and molecular dynamics simulations to study the interaction between AcrB and the compound MBX2319, a novel pyranopyridine efflux pump inhibitor with potent activity against RND efflux pumps of Enterobacteriaceae species, as well as other known inhibitors (D13-9001, 1-[1-naphthylmethyl]-piperazine, and phenylalanylarginine beta-naphthylamide) and the binding of doxorubicin to the efflux-defective F610A variant of AcrB. We also analyzed the binding of a substrate, minocycline, for comparison. Our results show that MBX2319 binds very tightly to the lower part of the distal pocket in the B protomer of AcrB, strongly interacting with the phenylalanines lining the hydrophobic trap, where the hydrophobic portion of D13 9001 was found to bind by X-ray crystallography. Additionally, MBX2319 binds to AcrB in a manner that is similar to the way in which doxorubicin binds to the F610A variant of AcrB. In contrast, 1-(1-naphthylmethyl)-piperazine and phenylalanylarginine-beta-naphthylamide appear to bind to somewhat different areas of the distal pocket in the B protomer of AcrB than does MBX2319. However, all inhibitors (except D13-9001) appear to distort the structure of the distal pocket, impairing the proper binding of substrates. PMID- 25114134 TI - UDP-N-acetylmuramic acid l-alanine ligase (MurC) inhibition in a tolC mutant Escherichia coli strain leads to cell death. AB - The Mur ligases play an essential role in the biosynthesis of bacterial peptidoglycan and hence are attractive antibacterial targets. A screen of the AstraZeneca compound library led to the identification of compound A, a pyrazolopyrimidine, as a potent inhibitor of Escherichia coli and Pseudomonas aeruginosa MurC. However, cellular activity against E. coli or P. aeruginosa was not observed. Compound A was active against efflux pump mutants of both strains. Experiments using an E. coli tolC mutant revealed accumulation of the MurC substrate and a decrease in the level of product upon treatment with compound A ,: indicating inhibition of MurC enzyme in these cells. Such a modulation was not observed in the E. coli wild-type cells. Further, overexpression of MurC in the E. coli tolC mutant led to an increase in the compound A MIC by >=16-fold, establishing a correlation between MurC inhibition and cellular activity. In addition, estimation of the intracellular compound A level showed an accumulation of the compound over time in the tolC mutant strain. A significant compound A level was not detected in the wild-type E. coli strain even upon treatment with high concentrations of the compound. Therefore, the lack of MIC and absence of MurC inhibition in wild-type E. coli were possibly due to suboptimal compound concentration as a consequence of a high efflux level and/or poor permeativity of compound A. PMID- 25114135 TI - A clinical adverse drug reaction prediction model for patients with chagas disease treated with benznidazole. AB - Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease, and the evidence supporting the benefits of BZN use during the chronic phase of the disease will favor its use in millions of individuals. However, more than 30% of patients treated with BZN may suffer adverse drug reactions (ADRs), and the development of tools to identify those patients at risk is highly desirable. In the present study, we aimed to identify predictive factors for ADRs in Chagas disease patients treated with BZN. Among 195 patients included in the study, 48.7% experienced ADRs and 31.3% had ADRs that caused BZN treatment discontinuation. Overall ADRs and ADRs that caused BZN treatment discontinuation were more common among women and in those who graduated from elementary school. Overall ADRs were also less frequent among black individuals. Based on logistic regression analysis, female sex (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.5 to 5.4), graduation from elementary school (OR, 2.0; 95% CI, 1.1 to 3.8), and white (OR, 5.0; 95% CI, 1.0 to 24.1) and mulatto (OR, 5.6; 95% CI, 1.1 to 28.7) races were considered to predict overall ADRs, and female sex (OR, 2.3; 95% CI, 1.2 to 4.3) was considered to predict ADRs that caused BZN treatment discontinuation. Graduation from elementary school also presented a tendency to predict ADRs that caused BZN treatment discontinuation (OR, 1.8; 95% CI, 0.9 to 3.6). The logistic regression (LR) models to predict ADRs to BZN described in this study may become important tools to minimize ADRs and improve patients' compliance and thus assist physicians treating patients with Chagas disease with BZN. PMID- 25114136 TI - Emergence of KPC-2-Producing Salmonella enterica Serotype Schwarzengrund in Argentina. PMID- 25114137 TI - Overproduction of Ristomycin A by activation of a silent gene cluster in Amycolatopsis japonicum MG417-CF17. AB - The emergence of antibiotic-resistant pathogenic bacteria within the last decades is one reason for the urgent need for new antibacterial agents. A strategy to discover new anti-infective compounds is the evaluation of the genetic capacity of secondary metabolite producers and the activation of cryptic gene clusters (genome mining). One genus known for its potential to synthesize medically important products is Amycolatopsis. However, Amycolatopsis japonicum does not produce an antibiotic under standard laboratory conditions. In contrast to most Amycolatopsis strains, A. japonicum is genetically tractable with different methods. In order to activate a possible silent glycopeptide cluster, we introduced a gene encoding the transcriptional activator of balhimycin biosynthesis, the bbr gene from Amycolatopsis balhimycina (bbrAba), into A. japonicum. This resulted in the production of an antibiotically active compound. Following whole-genome sequencing of A. japonicum, 29 cryptic gene clusters were identified by genome mining. One of these gene clusters is a putative glycopeptide biosynthesis gene cluster. Using bioinformatic tools, ristomycin (syn. ristocetin), a type III glycopeptide, which has antibacterial activity and which is used for the diagnosis of von Willebrand disease and Bernard-Soulier syndrome, was deduced as a possible product of the gene cluster. Chemical analyses by high-performance liquid chromatography and mass spectrometry (HPLC MS), tandem mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) spectroscopy confirmed the in silico prediction that the recombinant A. japonicum/pRM4-bbrAba synthesizes ristomycin A. PMID- 25114139 TI - resistome analysis of Enterobacter cloacae CY01, an extensively drug-resistant strain producing VIM-1 metallo-beta-lactamase from China. AB - Resistome analysis of clinical VIM-1-producing Enterobacter cloacae strain CY01 from China revealed the presence of multiple resistance determinants. Two resistance plasmids were identified in CY01. The pCY-VIM plasmid was 14 kb in size and possessed a replicase gene (repA), a gene cluster encoding the partitioning function (parABC), and a carbapenemase gene (blaVIM-1). Another 5.9 kb plasmid, pCY-MdT, with an aac(6')-Ib gene, was very closely related (13 nucleotide differences) to pMdT1, a ColE1 plasmid carrying aac(6')-Ib-cr4. PMID- 25114138 TI - Antimalarial activity of the myxobacterial macrolide chlorotonil a. AB - Myxobacteria are Gram-negative soil-dwelling bacteria belonging to the phylum Proteobacteria. They are a rich source of promising compounds for clinical application, such as epothilones for cancer therapy and several new antibiotics. In the course of a bioactivity screening program of secondary metabolites produced by Sorangium cellulosum strains, the macrolide chlorotonil A was found to exhibit promising antimalarial activity. Subsequently, we evaluated chlorotonil A against Plasmodium falciparum laboratory strains and clinical isolates from Gabon. Chlorotonil A was highly active, with a 50% inhibitory concentration between 4 and 32 nM; additionally, no correlations between the activities of chlorotonil A and artesunate (rho, 0.208) or chloroquine (rho, 0.046) were observed. Per os treatment of Plasmodium berghei-infected mice with four doses of as little as 36 mg of chlorotonil A per kg of body weight led to the suppression of parasitemia with no obvious signs of toxicity. Chlorotonil A acts against all stages of intraerythrocytic parasite development, including ring stage parasites and stage IV to V gametocytes, and it requires only a very short exposure to the parasite to exert its antimalarial action. Conclusively, chlorotonil A has an exceptional and unprecedented profile of action and represents an urgently required novel antimalarial chemical scaffold. Therefore, we propose it as a lead structure for further development as an antimalarial chemotherapeutic. PMID- 25114140 TI - Impact of lopinavir-ritonavir or nevirapine on bedaquiline exposures and potential implications for patients with tuberculosis-HIV coinfection. AB - Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patients are available. Plasma concentrations of bedaquiline and its M2 metabolite after single doses were obtained from interaction studies with nevirapine or LPV/r in healthy volunteers. The antiretrovirals' effects on bedaquiline and M2 pharmacokinetics were assessed by nonlinear mixed-effects modeling. Potential dose adjustments were evaluated with simulations. No significant effects of nevirapine on bedaquiline pharmacokinetics were identified. LPV/r decreased bedaquiline and M2 clearances to 35% (relative standard error [RSE], 9.2%) and 58% (RSE, 8.4%), respectively, of those without comedication. As almost 3-fold (bedaquiline) and 2-fold (M2) increases in exposures during chronic treatment with LPV/r are expected, dose adjustments are suggested for evaluation. Efficacious, safe bedaquiline dosing for MDR-TB patients receiving antiretrovirals is important. Modeling results suggest that bedaquiline can be coadministered with nevirapine without dose adjustments. The predicted elevation of bedaquiline and M2 levels during LPV/r coadministration may be a safety concern, and careful monitoring is recommended. Further data are being collected in coinfected patients to determine whether dose adjustments are needed. (These studies have been registered at ClinicalTrials.gov under registration numbers NCT00828529 [study C110] and NCT00910806 [study C117].). PMID- 25114141 TI - In vitro susceptibility of Plasmodium vivax to antimalarials in Colombia. AB - The in vitro susceptibilities of 30 isolates of Plasmodium vivax to a number of antimalarials (chloroquine [CQ], mefloquine, amodiaquine, quinine, and artesunate [AS]) were evaluated. The isolates came from the region of Uraba in Colombia, in which malaria is endemic, and were evaluated by the schizont maturation test. The 50% inhibitory concentration (IC50) was 0.6 nM (95% confidence interval [CI], 0.3 to 1.0 nM) for artesunate, 8.5 nM (95% CI, 5.6 to 13.0 nM) for amodiaquine, 23.3 nM (95% CI, 12.4 to 44.1 nM) for chloroquine, 55.6 nM (95% CI, 36.8 to 84.1 nM) for mefloquine, and 115.3 nM (95% CI, 57.7 to 230.5 nM) for quinine. The isolates were classified according to whether the initial parasites were mature or immature trophozoites (Tfz). It was found that the IC50s for chloroquine and artesunate were significantly different in the two aforementioned groups (P < 0.001). The IC50s of CQ and AS were higher in the isolates from mature Tfz (CQ, 39.3 nM versus 17 nM; AS, 1.4 nM versus 0.3 nM), and 10% of the isolates showed lower susceptibilities to one of the antimalarial drugs, 13.3% to two antimalarial drugs, and 3.3% to more than three antimalarial drugs. It should be highlighted that despite the extensive use of chloroquine in Colombia, P. vivax continues to be susceptible to antimalarials. This is the first report, to our knowledge, showing in vitro susceptibilities of P. vivax isolates to antimalarials in Colombia. PMID- 25114144 TI - Death of an alienist: Louis-Victor Marce's final year. AB - The cause of death, at the age of 37, of Louis-Victor Marce (1828-64), one of the most innovative alienists of the nineteenth century, was concealed by his contemporaries and colleagues. Recently it has been discovered that he committed suicide, but the circumstances and reasons for this were unknown. Information has now been found about his family, the events of the last year of his life and an unprecedented correspondence from his father-in-law, the chemist and academician Jules Pelouze, describing Marce's condition during the last month of his life. All of these point towards a diagnosis of melancholy, for which none of the appropriate measures were taken, probably as a result of the ailing Marce's social situation. PMID- 25114142 TI - Comparison of the antibiotic activities of Daptomycin, Vancomycin, and the investigational Fluoroquinolone Delafloxacin against biofilms from Staphylococcus aureus clinical isolates. AB - Biofilm-related infections remain a scourge. In an in vitro model of biofilms using Staphylococcus aureus reference strains, delafloxacin and daptomycin were found to be the most active among the antibiotics from 8 different pharmacological classes (J. Bauer, W. Siala, P. M. Tulkens, and F. Van Bambeke, Antimicrob. Agents Chemother. 57:2726-2737, 2013, doi:10.1128/AAC.00181-13). In this study, we compared delafloxacin to daptomycin and vancomycin using biofilms produced by 7 clinical strains (S. aureus epidemic clones CC5 and CC8) in order to rationalize the differences observed between the antibiotics and strains. The effects of the antibiotics on bacterial viability (resazurin reduction assay) and biomass (crystal violet staining) were measured and correlated with the proportion of polysaccharides in the matrix, the local microenvironmental pH (micro-pH), and the antibiotic penetration in the biofilm. At clinically meaningful concentrations, delafloxacin, daptomycin, and vancomycin caused a >=25% reduction in viability against the biofilms formed by 5, 4, and 3 strains, respectively. The antibiotic penetration within the biofilms ranged from 0.6 to 52% for delafloxacin, 0.2 to 10% for daptomycin, and 0.2 to 1% for vancomycin; for delafloxacin, this was inversely related to the polysaccharide proportion in the matrix. Six biofilms were acidic, explaining the high potency of delafloxacin (lower MICs at acidic pH). Norspermidine and norspermine (disassembling the biofilm matrix) drastically increased delafloxacin potency and efficacy (50% reduction in viability for 6 biofilms at clinically meaningful concentrations) in direct correlation with its increased penetration within the biofilm, while they only modestly improved daptomycin efficacy (50% reduction in viability for 2 biofilms) and penetration, and they showed marginal effects with vancomycin. Delafloxacin potency and efficacy against biofilms are benefited by its penetration into the matrix and the local acidic micro-pH. PMID- 25114145 TI - 'The world is full of big bad wolves': investigating the experimental therapeutic spaces of R.D. Laing and Aaron Esterson. AB - In conjunction with the recent critical assessments of the life and work of R.D. Laing, this paper seeks to demonstrate what is revealed when Laing's work on families and created spaces of mental health care are examined through a geographical lens. The paper begins with an exploration of Laing's time at the Tavistock Clinic in London during the 1960s, and of the co-authored text with Aaron Esterson entitled, Sanity, Madness and the Family (1964). The study then seeks to demonstrate the importance Laing and his colleague placed on the time space situatedness of patients and their worlds. Finally, an account is provided of Laing's and Esterson's spatial thinking in relation to their creation of both real and imagined spaces of therapeutic care. PMID- 25114143 TI - Evolution of oseltamivir resistance mutations in Influenza A(H1N1) and A(H3N2) viruses during selection in experimentally infected mice. AB - The evolution of oseltamivir resistance mutations during selection through serial passages in animals is still poorly described. Herein, we assessed the evolution of neuraminidase (NA) and hemagglutinin (HA) genes of influenza A/WSN/33 (H1N1) and A/Victoria/3/75 (H3N2) viruses recovered from the lungs of experimentally infected BALB/c mice receiving suboptimal doses (0.05 and 1 mg/kg of body weight/day) of oseltamivir over two generations. The traditional phenotypic and genotypic methods as well as deep-sequencing analysis were used to characterize the potential selection of mutations and population dynamics of oseltamivir resistant variants. No oseltamivir-resistant NA or HA changes were detected in the recovered A/WSN/33 viruses. However, we observed a positive selection of the I222T NA substitution in the recovered A/Victoria/3/75 viruses, with a frequency increasing over time and with an oseltamivir concentration from 4% in the initial pretherapy inoculum up to 28% after two lung passages. Although the presence of mixed I222T viral populations in mouse lungs only led to a minimal increase in oseltamivir 50% enzyme-inhibitory concentrations (IC50s) (by a mean of 5.7-fold) compared to that of the baseline virus, the expressed recombinant A/Victoria/3/75 I222T NA protein displayed a 16-fold increase in the oseltamivir IC50 level compared to that of the recombinant wild type (WT). In conclusion, the combination of serial in vivo passages under neuraminidase inhibitor (NAI) pressure and temporal deep-sequencing analysis enabled, for the first time, the identification and selection of the oseltamivir-resistant I222T NA mutation in an influenza H3N2 virus. Additional in vivo selection experiments with other antivirals and drug combinations might provide important information on the evolution of antiviral resistance in influenza viruses. PMID- 25114147 TI - Karl Jaspers on the disease entity: Kantian ideas and Weberian ideal types. AB - Jaspers' nosology is indebted to Immanuel Kant's theory of knowledge. He drew the distinction of form and content from the Transcendental Analytic of Kant's Critique of Pure Reason. The distinction is universal to all knowledge, including psychopathology. Individual experience is constituted by a form or category of the Understanding to give a determinate or knowable object classified into the generic type of a real disease entity. The application of form and content is limited by the boundaries of experience. Beyond this boundary are wholes whose conception requires Ideas of reason drawn from the Transcendental Dialectic. Wholes are regulated by Ideas of reason to give an object or schema of the Idea collected into ideal types of an ideal typical disease entity. Jaspers drew ideal types from Max Weber's social theory. He anticipated that, as knowledge advanced, ideal typical disease entities would become real disease entities. By 1920, this had been the destiny of general paralysis as knowledge of its neuropathology, serology and microbiology emerged. As he presented the final edition of General Psychopathology in 1946, Jaspers was anticipating the transition of schizophrenia from ideal typical to real disease entity. Almost 70 years later, with knowledge of its aetiology still unclear, schizophrenia remains marooned as an ideal typical disease entity - still awaiting that crucial advance! PMID- 25114146 TI - From paranoia querulans to vexatious litigants: a short study on madness between psychiatry and the law. Part 1. AB - The first part of this two-part paper presents a comparative history of paranoia querulans, also known as litigants' delusion, in German-speaking countries and France from the nineteenth century onwards. We first focus on two classic literary works which describe litigious behaviours that were later pathologized, then give an insight into the history of Querulantenwahn (litigants' delusion), a term coined in 1857 by Johann Ludwig Casper and adopted by German-speaking psychiatrists and forensic experts. The last section is devoted to its French equivalent, the delusion of the litigious persecuted-persecutors. We show how this category, widely popular among French fin-de-siecle alienists, was replaced by another: the delusion of revendication (litigious subtype). The history of the vexatious litigants in the English-speaking world will be explored in the Part 2. PMID- 25114149 TI - From the Netherlands to Japan: communicating psychiatric practice in the 1830s. AB - This article explores an example of the transmission of Dutch psychiatric knowledge to Japan in the Edo period (1600-1868), through the translation of a case study first published by Schroeder van der Kolk in 1826. The translation appeared in an innovative new journal of Western medicine edited by the Japanese rangaku (Dutch-learning) scholar, Mitsukuri Genpo. The case study describes the symptoms and treatment of a woman who experienced delusions following an ear infection, in terms largely familiar to the Japanese doctors of the time. This translation provides opportunities to consider the globalization and localization of psychiatric knowledge, the medicalization of mental health care in Japan, and the growing interest in Western psychiatry before its official introduction to Japan after 1868. PMID- 25114148 TI - Demonic possession and the historical construction of melancholy and hysteria. AB - Contrary to the often-voiced opinion that the birth of modern psychiatry should be regarded as a victory of enlightened science and rationality over outdated religious beliefs and ecclesiastical authority, it is argued in this article that the emergence of medical and psychiatric approaches to pathology in modernity takes place in the context of intensified religious life and mutual rivalry between the various religious denominations. Notably the two main types of demonological possession appearing in the context of Protestant and Catholic religious life, theological reflections and pastoral practices play a major role in the conceptualizations of melancholy and hysteria. The heritage of this can be viewed in the works of psychiatrists such as Charcot and Kraepelin, and also in Freud's psychoanalysis. PMID- 25114150 TI - J.H. Pons on 'Sympathetic insanity': With an introduction by GE Berrios. AB - The ancient concept of 'sympathy' originally referred to a putative affinity or force that linked all natural objects together. This notion was later used to explain the manner in which human beings related and felt for each other. A large literature exists on both the physical and psychological definitions of sympathy. Until the nineteenth century the conceptual apparatus of medicine preserved the view that the organs of the human body had a sympathetic affinity for each other. In addition to these 'physiological' (normal) sympathies there were morbid ones which explained the existence of various diseases. A morbid sympathy link also explained the fact that insanity followed the development of pathological changes in the liver, spleen, stomach and other bodily organs. These cases were classified as 'sympathetic insanities'. After the 1880s, the sympathy narrative was gradually replaced by physiological, endocrinological and psychodynamic explanations. The clinical states involved, however, are often observed in hospital practice and constitute the metier of 'consultation-liaison psychiatry'. Hence, it is surprising that historical work on the development of this discipline has persistently ignored the concept of 'sympathetic insanity'. PMID- 25114157 TI - Minicystis rosea gen. nov., sp. nov., a polyunsaturated fatty acid-rich and steroid-producing soil myxobacterium. AB - A bacterial strain designated SBNa008(T) was isolated from a Philippine soil sample. It exhibited the general characteristics associated with myxobacteria, such as swarming of Gram-negative vegetative rod cells, fruiting body and myxospore formation and predatory behaviour in lysing micro-organisms. The novel strain was characterized as mesophilic, chemoheterotrophic and aerobic. The major fatty acids were C(20:4)omega6,9,12,15 all cis (arachidonic acid), iso-C(15 : 0), C(17 : 1) 2-OH and iso-C(15 : 0) dimethylacetal. Interestingly, SBNa008(T) contained diverse fatty acids belonging to the commercially valuable polyunsaturated omega-6 and omega-3 families, and a highly conjugated dihydroxylated C28 steroid. The G+C content of the genomic DNA was 67.3 mol%. The 16S rRNA gene sequence revealed 95-96% similarity to sequences derived from clones of uncultured bacteria and 94-95% similarity to cultured members of the suborder Sorangiineae. Phylogenetic analysis revealed that strain SBNa008(T) formed a novel lineage in the suborder Sorangiineae. Based on a polyphasic taxonomic characterization, we propose that strain SBNa008(T) represents a novel genus and species, Minicystis rosea gen. nov., sp. nov. The type strain of Minicystis rosea is SBNa008(T) ( =DSM 24000(T) =NCCB 100349(T)). PMID- 25114159 TI - Demographic evidence of sex differences in vulnerability to infectious diseases. PMID- 25114158 TI - Mesoflavibacter sabulilitoris sp. nov., isolated from seashore sand. AB - A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated, gliding and rod-shaped bacterial strain, designated GJMS-9(T), was isolated from seashore sand collected at Geoje island in the South Sea, South Korea. Strain GJMS-9(T) grew optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 2.0% (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences revealed that strain GJMS-9(T) clustered with the type strain of Mesoflavibacter zeaxanthinifaciens, showing the highest sequence similarity of 99.1%. Strain GJMS-9(T) exhibited 16S rRNA gene sequence similarity of 96.5% to the type strain of Mesoflavibacter aestuarii and of less than 96.1% to the type strains of other recognized species. Strain GJMS-9(T) contained MK-6 as the only menaquinone and iso-C(15:1) G, iso C(16:0) 3-OH, iso-C(15:0) and iso-C(17:0) 3-OH as the major fatty acids. The polar lipid profile of strain GJMS-9(T) containing phosphatidylethanolamine, one unidentified lipid and one unidentified glycolipid as major components was similar to that of the type strain of M. zeaxanthinifaciens. The DNA G+C content of strain GJMS-9(T) was 32.2 mol% and its DNA-DNA relatedness with M. zeaxanthinifaciens DSM 18436(T) was 38 +/- 6.1%. The differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, revealed that strain GJMS-9(T) is separated from other species of the genus Mesoflavibacter. On the basis of the data presented, strain GJMS-9(T) is considered to represent a novel species of the genus Mesoflavibacter, for which the name Mesoflavibacter sabulilitoris sp. nov. is proposed. The type strain is GJMS-9(T) ( =KCTC 42117(T) =CECT 8597(T)). PMID- 25114160 TI - A multi-host approach for the systematic analysis of virulence factors in Cryptococcus neoformans. AB - A multi-host approach was followed to screen a library of 1201 signature-tagged deletion strains of Cryptococcus neoformans mutants to identify previously unknown virulence factors. The primary screen was performed using a Caenorhabditis elegans-C. neoformans infection assay. The hits among these strains were reconfirmed as less virulent than the wild type in the insect Galleria mellonella-C. neoformans infection assay. After this 2-stage screen, and to prioritize hits, we performed serial evaluations of the selected strains, using the C. elegans model. All hit strains identified through these studies were validated in a murine model of systemic cryptococcosis. Twelve strains were identified through a stepwise screening assay. Among them, 4 (CSN1201, SRE1, RDI1, and YLR243W) were previously discovered, providing proof of principle for this approach, while the role of the remaining 8 genes (CKS101, CNC5600, YOL003C, CND1850, MLH3, HAP502, MSL5, and CNA2580) were not previously described in cryptococcal virulence. The multi-host approach is an efficient method of studying the pathogenesis of C. neoformans. We used diverse model hosts, C. elegans, G. mellonella, and mice, with physiological differences and identified 12 genes associated with mammalian infection. Our approach may be suitable for large pathogenesis screens. PMID- 25114161 TI - Appropriateness of clopidogrel use according to current recommendations. AB - BACKGROUND: Clopidogrel is widely used in cardiovascular prevention. However, the prescription of clopidogrel in clinical practice does not match the recommendations concerning its indication and treatment duration. OBJECTIVE: To assess the appropriateness of clopidogrel prescription according to the accepted indications. METHODS: We undertook a retrospective observational analytical audit of the electronic clinical records in the region of Valencia, Spain (5 million inhabitants), selecting those patients on treatment with clopidogrel between 2007 and 2010. The primary outcome measure was the duration of the treatment. RESULTS: A total of 45721 patients started clopidogrel treatment during the study period. Treatment was for cardiologic disorders (CD) in 56.85% of the patients, neurologic disorders (ND) in 37.06% and peripheral arterial disease in 6.08%. Treatment duration was longer than that expected from clinical recommendations in 38.8% of the CD patients and 87.8% of the ND patients. The estimated avoidable cost ranged from 2 to 4.4 million Euros per year, according to whether a cheaper generic clopidogrel or a more expensive version was considered. CONCLUSIONS: Almost 40% of the cardiologic patients and 90% of the neurologic patients received excess treatment. Adjustment of treatment duration to international recommendations would result in savings of between 80.1 and 176.3 Euros per year and per patient treated. PMID- 25114163 TI - Initiation of rilpivirine, tenofovir and emtricitabine (RPV/TDF/FTC) regimen in 363 patients with virological vigilance assessment in 'real life'. AB - OBJECTIVES: To study the single-tablet regimen (STR) combination rilpivirine/tenofovir/emtricitabine (RPV/TDF/FTC) as soon as it became available. We describe a 14 month follow-up in a real clinical setting with a focus on resistance to RPV/TDF/FTC and polymorphisms associated with these drugs. METHODS: We estimated drug resistance at STR baseline by combining all available resistance tests, resulting in a cumulative virtual genotype. Physicians were advised of current or archived resistance mutations for the three drugs. Virological response was analysed according to resistance genotype at baseline. RESULTS: Three hundred and sixty-three patients received RPV/TDF/FTC; 79% had received previous treatment and RPV/TDF/FTC was the result of a switch of one drug to rilpivirine in two-thirds of cases. The cumulative genotype showed 4% of rilpivirine resistance mutations at baseline and 16% of polymorphisms concerning non-nucleoside reverse transcriptase inhibitors (NNRTIs). With a median duration of STR of 8 months, 78% of patients with these polymorphisms were virologically suppressed compared with 96% with wild-type genotypes. Five genotypes were determined during the follow-up, revealing three rilpivirine resistance associated mutations: E138Q/Y181I, M230L and K101P (potentially with a K101Q intermediate). CONCLUSIONS: This observational study reflects routine clinical practice and the relevance of virological advice. It also confirms the efficacy of this STR (RPV/TDF/FTC) for naive and virologically suppressed pretreated patients with a low prevalence of virological failure and resistance if the cumulative baseline genotype is free of resistance to NNRTIs and/or polymorphisms associated with NNRTIs. PMID- 25114162 TI - HMBPP-deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vgamma2Vdelta2 T cells. AB - Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vgamma2Vdelta2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vgamma2Vdelta2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria DeltaactA prfA* and HMBPP-deficient Listeria DeltaactA DeltaGCPE: prfA* mutant. The HMBPP-deficient DeltaGCPE: mutant shows lower ability to expand Vgamma2Vdelta2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vgamma2Vdelta2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vgamma2Vdelta2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP deficient listeria differentiated fewer Vgamma2Vdelta2 T effector cells capable of coproducing IFN-gamma and TNF-alpha and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vgamma2Vdelta2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vgamma2Vdelta2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention. PMID- 25114164 TI - Antibiotic prophylaxis for transrectal prostate biopsy-a new strategy. AB - BACKGROUND: Fluoroquinolones are extensively used as prophylaxis for transrectal ultrasound-guided biopsy of the prostate (TRUBP). Emerging fluoroquinolone resistance and selection of multiresistant organisms warrant new prophylactic strategies. Pivmecillinam and amoxicillin/clavulanic acid have mutual synergistic activity and the combination of these agents has a broad coverage of the majority of microorganisms causing infectious complications after TRUBP and may be a valuable future prophylactic regimen. PATIENTS AND METHODS: This was a retrospective cohort study of 2624 men that underwent TRUBP at a Danish university hospital. The patients were divided into three groups. Group 1 (n = 1220) received ciprofloxacin before TRUBP, Group 2 (n = 240) received a combination of pivmecillinam and amoxicillin/clavulanic acid before TRUBP and Group 3 (n = 1161) received an extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid before and for 2 days after TRUBP. RESULTS: One hundred and ten out of 148 (74.3%) post-TRUBP infections were caused by Escherichia coli, Klebsiella pneumoniae or Enterococcus faecalis. Group 3 with the extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid had a significantly lower rate of bacteraemia (0.9%) as compared with Group 1 (1.8%) and Group 2 (3.7%). A significant fall in the proportion of ESBL-producing Enterobacteriaceae was observed from the period when ciprofloxacin was used as prophylaxis (8.1%) compared with the subsequent period when pivmecillinam and amoxicillin/clavulanic acid was used (5.9%). CONCLUSIONS: The combination of pivmecillinam and amoxicillin/clavulanic acid is an attractive prophylaxis for TRUBP from a clinical, bacteriological and ecological point of view as compared with ciprofloxacin. PMID- 25114165 TI - Kinetics of recA and recX induction in drug-susceptible and MDR clinical strains of Mycobacterium tuberculosis. AB - OBJECTIVES: To investigate and compare the expression of recA and recX, components of the SOS pathway, following rifampicin treatment in drug-susceptible and MDR clinical strains of Mycobacterium tuberculosis. METHODS: Strains (M. tuberculosis and Mycobacterium smegmatis) were subjected to rifampicin- and mitomycin-induced stress for 36 h followed by RNA extraction. recA and recX in the RNA extract were estimated using qRT-PCR. RESULTS: The MDR clinical strain induced faster (24 h) and higher (7-fold) levels of recA as compared with the drug-susceptible strain (36 h) in response to rifampicin. recX levels were found to rise with an increase in levels of recA; however, the levels were relatively higher than recA. CONCLUSIONS: Drug-susceptible and MDR strains have different kinetics of induction of DNA repair. PMID- 25114166 TI - Proteus genomic island 1 (PGI1), a new resistance genomic island from two Proteus mirabilis French clinical isolates. AB - OBJECTIVES: To analyse the genetic environment of the antibiotic resistance genes in two clinical Proteus mirabilis isolates resistant to multiple antibiotics. METHODS: PCR, gene walking and whole-genome sequencing were used to determine the sequence of the resistance regions, the surrounding genetic structure and the flanking chromosomal regions. RESULTS: A genomic island of 81.1 kb named Proteus genomic island 1 (PGI1) located at the 3'-end of trmE (formerly known as thdF) was characterized. The large MDR region of PGI1 (55.4 kb) included a class 1 integron (aadB and aadA2) and regions deriving from several transposons: Tn2 (blaTEM-135), Tn21, Tn6020-like transposon (aphA1b), a hybrid Tn502/Tn5053 transposon, Tn501, a hybrid Tn1696/Tn1721 transposon [tetA(A)] carrying a class 1 integron (aadA1) and Tn5393 (strA and strB). Several ISs were also present (IS4321, IS1R and IS26). The PGI1 backbone (25.7 kb) was identical to that identified in Salmonella Heidelberg SL476 and shared some identity with the Salmonella genomic island 1 (SGI1) backbone. An IS26-mediated recombination event caused the division of the MDR region into two parts separated by a large chromosomal DNA fragment of 197 kb, the right end of PGI1 and this chromosomal sequence being in inverse orientation. CONCLUSIONS: PGI1 is a new resistance genomic island from P. mirabilis belonging to the same island family as SGI1. The role of PGI1 in the spread of antimicrobial resistance genes among Enterobacteriaceae of medical importance needs to be evaluated. PMID- 25114167 TI - Pharmacokinetics of oral isavuconazole in a patient after Roux-en-Y gastric bypass surgery. PMID- 25114168 TI - A multisystem investigation of raltegravir association with intestinal tissue: implications for pre-exposure prophylaxis and eradication. AB - OBJECTIVES: Recent clinical data have suggested high raltegravir concentrations in gut tissue after oral administration, with implications for treatment and prevention. We have used in silico, in vitro, ex vivo and in vivo models to further investigate the accumulation of raltegravir in gut tissue. METHODS: Affinity of raltegravir for gut tissue was assessed in silico (Poulin-Theil method), in vitro (Caco-2 accumulation) and ex vivo (rat intestine) and compared with the lipophilic drug lopinavir. Finally, raltegravir concentrations in plasma, gut contents, small intestine and large intestine were determined after oral dosing to Wistar rats 1 and 4 h post-dose. Samples were analysed using LC MS/MS and scintillation counting. RESULTS: Gut tissue accumulation of raltegravir was less than for lopinavir in silico, in vitro and ex vivo (P < 0.05). After oral administration to rats, raltegravir concentrations 4 h post-dose were lower in plasma (0.05 MUM) compared with small intestine (0.47 MUM, P = 0.06) and large intestine (1.36 MUM, P < 0.05). However, raltegravir concentrations in the contents of both small intestine (4.0 MUM) and large intestine (40.6 MUM) were also high. CONCLUSIONS: In silico, in vitro and ex vivo data suggest low raltegravir accumulation in intestinal tissue. In contrast, in vivo animal data suggest raltegravir concentrates in intestinal tissue even when plasma concentrations are minimal. However, high raltegravir concentrations in gut contents are the likely driving factor behind this observation, rather than blood to-tissue drug distribution. The methods described can be combined with clinical investigations to provide a complete strategy for selection of drugs with high gut accumulation. PMID- 25114169 TI - Separation and quantification of 2-acyl-1-lysophospholipids and 1-acyl-2 lysophospholipids in biological samples by LC-MS/MS. AB - Lysophospholipids (LysoGPs) serve as lipid mediators and precursors for synthesis of diacyl phospholipids (GPs). LysoGPs detected in cells have various acyl chains attached at either the sn-1 or sn-2 position of the glycerol backbone. In general, acyl chains at the sn-2 position of 2-acyl-1-LysoGPs readily move to the sn-1 position, generating 1-acyl-2-lyso isomers by a nonenzymatic reaction called intra-molecular acyl migration, which has hampered the detection of 2-acyl-1 LysoGPs in biological samples. In this study, we developed a simple and versatile method to separate and quantify 2-acyl-1- and 1-acyl-2-LysoGPs. The main point of the method was to extract LysoGPs at pH 4 and 4 degrees C, conditions that were found to completely eliminate the intra-molecular acyl migration. Under the present conditions, the relative amounts of 2-acyl-1-LysoGPs and 1-acyl-2-LysoGPs did not change at least for 1 week. Further, in LysoGPs extracted from cells and tissues under the present conditions, most of the saturated fatty acids (16:0 and 18:0) were found in the sn-1 position of LysoGPs, while most of the PUFAs (18:2, 20:4, 22:6) were found in the sn-2 position. Thus the method can be used to elucidate the in vivo role of 2-acyl-1-LysoGPs. PMID- 25114170 TI - Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver. AB - Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed in highly oxi-dative tissues and is poised to modulate mitochondrial FA oxidation (FAO), yet its biological role is unknown. Using a model of adenoviral Acot2 overexpression in mouse liver (Ad-Acot2), we show that Acot2 increases the utilization of FA substrate during the daytime in ad libitum-fed mice, but the nighttime switch to carbohydrate oxidation is similar to control mice. In further support of elevated FAO in Acot2 liver, daytime serum ketones were higher in Ad Acot2 mice, and overnight fasting led to minimal hepatic steatosis as compared with control mice. In liver mitochondria from Ad-Acot2 mice, phosphorylating O2 consumption was higher with lipid substrate, but not with nonlipid substrate. This increase depended on whether FA could be activated on the outer mitochondrial membrane, suggesting that the FA released by Acot2 could be effluxed from mitochondria then taken back up again for oxidation. This circuit would prevent the build-up of inhibitory long-chain fatty acyl-CoA esters. Altogether, our findings indicate that Acot2 can enhance FAO, possibly by mitigating the accumulation of FAO intermediates within the mitochondrial matrix. PMID- 25114173 TI - A reciprocal antagonism between miR-376c and TGF-beta signaling regulates neural differentiation of human pluripotent stem cells. AB - Differentiation of neural lineages from human pluripotent stem cells (hPSCs) raises the hope of generating functional cells for the treatment of neural diseases. However, current protocols for differentiating hPSCs into neural lineages remain inefficient and largely variable between different hPSC lines. We report that microRNA 376c (miR-376c) significantly enhanced neural differentiation of hPSCs in a defined condition by suppressing SMAD4, the co-SMAD for TGF-beta signaling. Downstream, SMAD4 directly bound and suppressed PAX6, the critical neural lineage specification factor. Interestingly, we also found that SMAD4 binds and suppresses miR-376c clusters in undifferentiated hESCs. In summary, our findings revealed a reciprocal antagonism between miR-376c and SMAD signaling that regulates cell fate during human neural differentiation. PMID- 25114171 TI - Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity. AB - Adipogenesis plays a critical role in the initiation and progression of obesity. Although cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have emerged as a potential therapeutic target for cardiometabolic disease, the functional contribution of EETs to adipogenesis and the pathogenesis of obesity remain poorly understood. Our studies demonstrated that induction of adipogenesis in differentiated 3T3-L1 cells (in vitro) and obesity-associated adipose expansion in high-fat diet (HFD)-fed mice (in vivo) significantly dysregulate the CYP epoxygenase pathway and evoke a marked suppression of adipose-derived EET levels. Subsequent in vitro experiments demonstrated that exogenous EET analog administration elicits potent anti-adipogenic effects via inhibition of the early phase of adipogenesis. Furthermore, EET analog administration to mice significantly mitigated HFD-induced weight gain, adipose tissue expansion, pro adipogenic gene expression, and glucose intolerance. Collectively, these findings suggest that suppression of EET bioavailability in adipose tissue is a key pathological consequence of obesity, and strategies that promote the protective effects of EETs in adipose tissue offer enormous therapeutic potential for obesity and its downstream pathological consequences. PMID- 25114174 TI - Exploration of salivary proteins in buffalo: an approach to find marker proteins for estrus. AB - Saliva is considered as the best source of biological material for biomarker discovery studies since it is noninvasive in comparison to other body sources. Usually buffalo cannot precisely express estrus signals. Hence, there is a need for concise methods to detect the time of estrus to ensure the success of artificial insemination. Therefore, we have established a reference proteome map on the whole saliva of buffalo during their estrous cycle with special reference to estrus. Nearly 12 bands have been observed using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of whole saliva. Collectively, 179 proteins are identified with respect to different phases of the estrous cycle using mass spectrometry. On the whole, 37 proteins are exclusively expressed in the estrus phase, which include beta-enolase, Toll-like receptor (TLR) 4, clusterin, lactoperoxidase, serotransferrin, TGM3, UBA6, and transducin. Among the proteins, beta-enolase and TLR 4 were validated, and their specific expression was found during estrus as compared to other phases using immunoblot. The functional annotation reveals many as binding proteins in the estrus saliva when compared to the other phases. The present findings conclude that the proteomic approach adopted to identify the proteins from buffalo saliva around the estrous cycle may provide a new tool for screening the estrus phase. The results further conclude that the specific expression of beta-enolase and TLR 4 can be taken as the indicator of estrus in buffalo. PMID- 25114172 TI - Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells. AB - Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high arachidonic acid (AA) content. Here, we investigated the functional role of adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as substrate for eicosanoid generation by activated human primary MCs in culture. Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in LDs. IgE-dependent activation of MCs triggered the secretion of the two major eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate release of PGD2 from the activated MCs was solely dependent on cyclooxygenase (COX) 1, while during the delayed phase of lipid mediator production, the inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced MCs were activated, the secretion of both PGD2 and LTC4 was significantly reduced. Interestingly, the inhibitory effect on the release of LTC4 was even more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A2-silenced MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC LDs and define ATGL as a novel regulator of the substrate availability of AA for eicosanoid generation upon MC activation. PMID- 25114175 TI - Structure of Toxoplasma gondii coronin, an actin-binding protein that relocalizes to the posterior pole of invasive parasites and contributes to invasion and egress. AB - Coronins are involved in the regulation of actin dynamics in a multifaceted way, participating in cell migration and vesicular trafficking. Apicomplexan parasites, which exhibit an actin-dependent gliding motility that is essential for traversal through tissues, as well as invasion of and egress from host cells, express only a single coronin, whereas higher eukaryotes possess several isoforms. We set out to characterize the 3-D structure, biochemical function, subcellular localization, and genetic ablation of Toxoplasma gondii coronin (TgCOR), to shed light on its biological role. A combination of X-ray crystallography, small-angle scattering of X-rays, and light scattering revealed the atomic structure of the conserved WD40 domain and the dimeric arrangement of the full-length protein. TgCOR binds to F-actin and increases the rate and extent of actin polymerization. In vivo, TgCOR relocalizes transiently to the posterior pole of motile and invading parasites, independent of actin dynamics, but concomitant to microneme secretory organelle discharge. TgCOR contributes to, but is not essential for, invasion and egress. Taken together, our data point toward a role for TgCOR in stabilizing newly formed, short filaments and F-actin cross linking, as well as functions linked to endocytosis and recycling of membranes. PMID- 25114176 TI - TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel. AB - Transient receptor potential (TRP) channels, a superfamily of ion channels, can be divided into 7 subfamilies, including TRPV, TRPC, TRPP, and 4 others. Functional TRP channels are tetrameric complexes consisting of 4 pore-forming subunits. The purpose of this study was to explore the heteromerization of TRP subunits crossing different TRP subfamilies. Two-step coimmunoprecipitation (co IP) and fluorescence resonance energy transfer (FRET) were used to determine the interaction of the different TRP subunits. Patch-clamp and cytosolic Ca(2+) measurements were used to determine the functional role of the ion channels in flow conditions. The analysis demonstrated the formation of a heteromeric TRPV4 C1-P2 complex in primary cultured rat mesenteric artery endothelial cells (MAECs) and HEK293 cells that were cotransfected with TRPV4, TRPC1, and TRPP2. In functional experiments, pore-dead mutants for each of these 3 TRP isoforms nearly abolished the flow-induced cation currents and Ca(2+) increase, suggesting that all 3 TRPs contribute to the ion permeation pore of the channels. We identified the first heteromeric TRP channels composed of subunits from 3 different TRP subfamilies. Functionally, this heteromeric TRPV4-C1-P2 channel mediates the flow induced Ca(2+) increase in native vascular endothelial cells. PMID- 25114177 TI - A novel CRIg-targeted complement inhibitor protects cells from complement damage. AB - The inappropriate activation of complement may contribute to various immune diseases. The alternative pathway (AP) predominates during complement activation regardless of the initiating pathways. Hence, the main AP regulator factor H (FH) holds great potential as an attractive therapeutic intervention. In addition, complement receptor of the immunoglobulin superfamily (CRIg) has been demonstrated to inhibit AP and, more notably, still specifically binds to C3b/iC3b. We thus developed novel CRIg-targeted complement inhibitors by connecting the functional domains of CRIg and FH, which we termed CRIg-FH and CRIg-L-FH. CRIg-L-FH, slightly more potent than CRIg-FH, considerably inhibited both AP- and also classical pathway (CP)-mediated hemolysis and successfully eliminated the deposition of C3b/iC3b. Kinetic analysis further revealed that the binding affinity constant (KD) of CRIg/FH was in the micromolar range, consistent with its long-lasting binding to complement-attacked cells. CRIg-L-FH efficiently protected aberrant erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH) from AP- and CP-mediated complement damage (IC50 was 22.43 and 64.69 nM, respectively). Moreover, CRIg-L-FH was found to inhibit complement activation induced by the anti-Thy1 antibody in a mesangioproliferative glomerulonephritis (MPGN) rat model. Hence, CRIg-L-FH protects glomerular mesangial cells (GMCs) from complement-mediated injury and proliferative lesions. These findings strongly suggest that CRIg/FH is a potential therapeutic drug candidate for a range of complement-mediated diseases. PMID- 25114178 TI - An intracellular antifreeze protein from an Antarctic microalga that responds to various environmental stresses. AB - The structure and function of the Antarctic marine diatom Chaetoceros neogracile antifreeze protein (Cn-AFP), as well as its expression levels and characteristics of the ice-binding site, were analyzed in the present study. In silico analysis revealed that the Cn-AFP promoter contains both light- and temperature-responsive elements. Northern and Western blot analyses demonstrated that both Cn-AFP transcript and protein expression were strongly and rapidly stimulated by freezing, as well as temperature and high light stress. Immunogold labeling revealed that Cn-AFP is preferentially localized to the intracellular space near the chloroplast membrane. Recombinant Cn-AFP had clear antifreeze activity. Protein-folding simulation was used to predict the putative ice-binding sites in Cn-AFP, and site-directed mutagenesis of the Cn-AFP b-face confirmed their identification. PMID- 25114179 TI - Functional and structural characterization of the kinase insert and the carboxy terminal domain in VEGF receptor 2 activation. AB - Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development and homeostasis. VEGF receptor 2 (VEGFR-2) is the major receptor involved in vasculogenesis and angiogenesis and regulates endothelial cell survival, migration, and mitogenesis. Ligand-mediated receptor dimerization instigates transmembrane signaling, thereby promoting activation of the intracellular kinase domain. The intracellular part of the receptor comprises the juxtamembrane domain, the catalytic kinase domain, the kinase insert domain (KID), and the carboxy terminal domain (CD). Here we show that the CD inhibits VEGFR-2 activity in the absence of ligand, whereas the KID, particularly a tyrosine residue in this domain (Y951), is indispensable for downstream signaling by the activated kinase. Because of the lack of crystallographic data for the complete kinase domain, we applied size-exclusion chromatography, multiangle laser scattering, analytical ultracentrifugation, and small-angle X-ray scattering to build and functionally validate structural models. Our data show substantial conformational changes of the kinase when it is switched from the inactive, unphosphorylated state to the active, phosphorylated state. Finally, we structurally characterized recombinantly produced protein complexes between VEGFR 2 and T cell-specific adapter protein, a molecule involved in downstream signaling by VEGFR-2. PMID- 25114180 TI - Inducible factors with antimicrobial activity after immune challenge in the haemolymph of Red Palm Weevil (Insecta). AB - Insects are capable of innate immune responses elicited after microbial infection. In this process, the receptor-mediated recognition of foreign bodies and the subsequent activation of immunocompetent cells lead to the synthesis ex novo of a peptide pool with antimicrobial activity. We investigated the inducible immune response of a coleopteran, Rhynchophorus ferrugineus, challenged with both Gram-negative and Gram-positive bacteria. After immunization, we evaluated the presence of antimicrobial peptides using either biochemical analyses or microbiological techniques. The antimicrobial properties of the newly synthesized protein pool, detectable in haemolymph fractions of low molecular mass, showed strong antibacterial activity against various bacterial strains (Escherichia coli, Pseudomonas sp. OX1, Bacillus subtilis and Micrococcus luteus). In addition to the preliminary study of the mechanism of action of the pool of antimicrobial peptides, we also investigated its effects on bacterial cell walls by means of fluorescence microscopy and scanning electron microscopy. The data suggest that the main effects seem to be directed at destabilizing and damaging the bacterial wall. This study provides data that help us to understand some aspects of the inducible innate immunity in a system model that lacks anticipatory responses. However, the weevil has finely tuned its defensive strategies to counteract effectively microbial infection. PMID- 25114181 TI - The IOC Centres of Excellence bring prevention to sports medicine. AB - The protection of an athlete's health and preventing injuries and illnesses in sport are top priorities for the IOC and its Medical Commission. The IOC therefore partners with selected research centres around the world and supports research in the field of sports medicine. This has enabled the IOC to develop an international network of expert scientists and clinicians in sports injury and disease prevention research. The IOC wants to promote injury and disease prevention and the improvement of physical health of the athlete by: (1) establishing long-term research programmes on injury and disease prevention (including studies on basic epidemiology, risk factors, injury mechanisms and intervention), (2) fostering collaborative relationships with individuals, institutions and organisations to improve athletes' health, (3) implementing and collaborating with applied, ongoing and novel research and development within the framework and long-term strategy of the IOC and (4) setting up knowledge translation mechanisms to share scientific research results with the field throughout the Olympic Movement and sports community and converting these results into concrete actions to protect the health of the athletes. In 2009, the IOC also identified four research centres that had an established track record in research, educational and clinical activities to achieve these ambitions: (1) the Australian Centre for Research into Injury in Sport and its Prevention (ACRISP), Australia; (2) the Sport Injury Prevention Research Centre (SIPRC), Canada; (3) the Clinical Sport and Exercise Medicine Research (CSEM), South Africa and (4) the Oslo Sports Trauma Research Center (OSTRC), Norway. This paper highlights the work carried out by these four IOC Centres of Excellence over the past 6 years and their contribution to the world of sports medicine. PMID- 25114183 TI - Republished research: Impact of autologous blood injections in treatment of mid portion Achilles tendinopathy: double blind randomised controlled trial. AB - STUDY QUESTION: Do peritendinous autologous blood injections improve pain and function in people with mid-portion Achilles tendinopathy? SUMMARY ANSWER: The administration of two unguided peritendinous autologous blood injections one month apart, in addition to a standardised eccentric training programme, provides no additional benefit in the treatment of mid-portion Achilles tendinopathy. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Several studies have suggested that injection of autologous blood can help in the treatment of various tendinopathies. There is a lack of high quality evidence showing relevant benefit for autologous blood injections, particularly in the management of mid-portion Achilles tendinopathy. We found no additional reduction in pain or improvement in function when these injections were combined with an eccentric calf training programme. PMID- 25114184 TI - Extensive blueberry muffin rash in a neonate. PMID- 25114185 TI - The current status of neonatal organ donation in the UK. PMID- 25114187 TI - Varicose veins. PMID- 25114186 TI - Novel wireless devices for cardiac monitoring. PMID- 25114188 TI - ECG Response: August 12, 2014. PMID- 25114190 TI - Pseudo-pre-excitation unraveled down to its core. PMID- 25114189 TI - Left ventricular hypertrophy in a runner: things are not always what they seem. PMID- 25114191 TI - Cardiology patient page. Varicose veins. PMID- 25114192 TI - Letter by Takahashi regarding article "targeting interleukin-1 in heart disease". PMID- 25114193 TI - Response to letter regarding article, "targeting interleukin-1 in heart disease". PMID- 25114197 TI - Neurology in Africa. PMID- 25114196 TI - In vitro and in vivo evaluation of a novel collagen/cellulose nanocrystals scaffold for achieving the sustained release of basic fibroblast growth factor. AB - Tissue-engineered dermis is thought to be the best treatment for skin defects; however, slow vascularization of these biomaterial scaffolds limits their clinical application. Exogenous administration of angiogenic growth factors is highly desirable for tissue regeneration. In this study, biodegradable gelatin microspheres (GMs) containing basic fibroblast growth factor (bFGF) were fabricated and incorporated into a porous collagen/cellulose nanocrystals (CNCs) scaffold, as a platform for long-term release and consequent angiogenic boosting. The physicochemical properties of these scaffolds were examined and the in vitro release pattern of bFGF from scaffolds was measured by ELISA. Collagen/CNCs scaffolds with and without bFGF-GMs were incubated with human umbilical vein endothelial cells for 1 week, results showed that the scaffolds with bFGF-GMs significantly augmented cell proliferation. Then, four different groups of scaffolds were implanted subcutaneously into Sprague-Dawley rats to study angiogenesis in vivo via macroscopic observation, and hematoxylin and eosin and immunohistochemical staining. The results suggested that the collagen/CNCs/bFGF GMs scaffolds had a significantly higher number of newly formed and mature blood vessels, and the fastest degradation rate. This study demonstrated that collagen/CNCs/bFGF-GMs scaffolds have great potential in skin tissue engineering. PMID- 25114198 TI - Inflammatory neurologic disease in sub-Saharan Africa. PMID- 25114199 TI - Prune belly and schizencephaly. PMID- 25114200 TI - Wrong side dilated pupil. PMID- 25114201 TI - Clinical Reasoning: An unusual cause of transverse myelitis? PMID- 25114203 TI - Clinical Reasoning: A 38-year-old woman with childhood-onset weakness. PMID- 25114204 TI - Teaching NeuroImages: Infantile herpes simplex encephalitis. PMID- 25114205 TI - Teaching NeuroImages: Ocular bruit in carotid-cavernous sinus fistula. PMID- 25114206 TI - Recent research on the growth plate: Advances in fibroblast growth factor signaling in growth plate development and disorders. AB - Skeletons are formed through two distinct developmental actions, intramembranous ossification and endochondral ossification. During embryonic development, most bone is formed by endochondral ossification. The growth plate is the developmental center for endochondral ossification. Multiple signaling pathways participate in the regulation of endochondral ossification. Fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling has been found to play a vital role in the development and maintenance of growth plates. Missense mutations in FGFs and FGFRs can cause multiple genetic skeletal diseases with disordered endochondral ossification. Clarifying the molecular mechanisms of FGFs/FGFRs signaling in skeletal development and genetic skeletal diseases will have implications for the development of therapies for FGF-signaling-related skeletal dysplasias and growth plate injuries. In this review, we summarize the recent advances in elucidating the role of FGFs/FGFRs signaling in growth plate development, genetic skeletal disorders, and the promising therapies for those genetic skeletal diseases resulting from FGFs/FGFRs dysfunction. Finally, we also examine the potential important research in this field in the future. PMID- 25114207 TI - Recent research on the growth plate: Mechanisms for growth plate injury repair and potential cell-based therapies for regeneration. AB - Injuries to the growth plate cartilage often lead to bony repair, resulting in bone growth defects such as limb length discrepancy and angulation deformity in children. Currently utilised corrective surgeries are highly invasive and limited in their effectiveness, and there are no known biological therapies to induce cartilage regeneration and prevent the undesirable bony repair. In the last 2 decades, studies have investigated the cellular and molecular events that lead to bony repair at the injured growth plate including the identification of the four phases of injury repair responses (inflammatory, fibrogenic, osteogenic and remodelling), the important role of inflammatory cytokine tumour necrosis factor alpha in regulating downstream repair responses, the role of chemotactic and mitogenic platelet-derived growth factor in the fibrogenic response, the involvement and roles of bone morphogenic protein and Wnt/B-catenin signalling pathways, as well as vascular endothelial growth factor-based angiogenesis during the osteogenic response. These new findings could potentially lead to identification of new targets for developing a future biological therapy. In addition, recent advances in cartilage tissue engineering highlight the promising potential for utilising multipotent mesenchymal stem cells (MSCs) for inducing regeneration of injured growth plate cartilage. This review aims to summarise current understanding of the mechanisms for growth plate injury repair and discuss some progress, potential and challenges of MSC-based therapies to induce growth plate cartilage regeneration in combination with chemotactic and chondrogenic growth factors and supporting scaffolds. PMID- 25114208 TI - Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. PMID- 25114209 TI - Murine CD27(-) Vgamma6(+) gammadelta T cells producing IL-17A promote ovarian cancer growth via mobilization of protumor small peritoneal macrophages. AB - Cancer-associated inflammation mobilizes a variety of leukocyte populations that can inhibit or enhance tumor cell growth in situ. These subsets include gammadelta T cells, which can infiltrate tumors and typically provide large amounts of antitumor cytokines, such as IFN-gamma. By contrast, we report here that in a well-established transplantable (ID8 cell line) model of peritoneal/ovarian cancer, gammadelta T cells promote tumor cell growth. gammadelta T cells accumulated in the peritoneal cavity in response to tumor challenge and could be visualized within solid tumor foci. Functional characterization of tumor-associated gammadelta T cells revealed preferential production of interleukin-17A (IL-17), rather than IFN-gamma. Consistent with this finding, both T cell receptor (TCR)delta-deficient and IL-17-deficient mice displayed reduced ID8 tumor growth compared with wild-type animals. IL-17 production by gammadelta T cells in the tumor environment was essentially restricted to a highly proliferative CD27((-)) subset that expressed Vgamma6 instead of the more common Vgamma1 and Vgamma4 TCR chains. The preferential expansion of IL-17-secreting CD27((-)) Vgamma6((+)) gammadelta T cells associated with the selective mobilization of unconventional small peritoneal macrophages (SPMs) that, in comparison with large peritoneal macrophages, were enriched for IL-17 receptor A, and for protumor and proangiogenic molecular mediators, which were up-regulated by IL-17. Importantly, SPMs were uniquely and directly capable of promoting ovarian cancer cell proliferation. Collectively, this work identifies an IL-17-dependent lymphoid/myeloid cross-talk involving gammadelta T cells and SPMs that promotes tumor cell growth and thus counteracts cancer immunosurveillance. PMID- 25114212 TI - Modeling morphological diversity in the oldest large multicellular organisms. PMID- 25114210 TI - Characterizing the proton loading site in cytochrome c oxidase. AB - Cytochrome c oxidase (CcO) uses the energy released by reduction of O2 to H2O to drive eight charges from the high pH to low pH side of the membrane, increasing the electrochemical gradient. Four electrons and protons are used for chemistry, while four more protons are pumped. Proton pumping requires that residues on a pathway change proton affinity through the reaction cycle to load and then release protons. The protonation states of all residues in CcO are determined in MultiConformational Continuum Electrostatics simulations with the protonation and redox states of heme a, a3, Cu(B), Y288, and E286 used to define the catalytic cycle. One proton is found to be loaded and released from residues identified as the proton loading site (PLS) on the P-side of the protein in each of the four CcO redox states. Thus, the same proton pumping mechanism can be used each time CcO is reduced. Calculations with structures of Rhodobacter sphaeroides, Paracoccus denitrificans, and bovine CcO derived by crystallography and molecular dynamics show the PLS functions similarly in different CcO species. The PLS is a cluster rather than a single residue, as different structures show 1-4 residues load and release protons. However, the proton affinity of the heme a3 propionic acids primarily determines the number of protons loaded into the PLS; if their proton affinity is too low, less than one proton is loaded. PMID- 25114211 TI - Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. AB - SUMOylation is an essential ubiquitin-like modification involved in important biological processes in eukaryotic cells. Identification of small ubiquitin related modifier (SUMO)-conjugated residues in proteins is critical for understanding the role of SUMOylation but remains experimentally challenging. We have set up a powerful and high-throughput method combining quantitative proteomics and peptide immunocapture to map SUMOylation sites and have analyzed changes in SUMOylation in response to stimuli. With this technique we identified 295 SUMO1 and 167 SUMO2 sites on endogenous substrates of human cells. We further used this strategy to characterize changes in SUMOylation induced by listeriolysin O, a bacterial toxin that impairs the host cell SUMOylation machinery, and identified several classes of host proteins specifically deSUMOylated in response to this toxin. Our approach constitutes an unprecedented tool, broadly applicable to various SUMO-regulated cellular processes in health and disease. PMID- 25114213 TI - Vectored antibody gene delivery protects against Plasmodium falciparum sporozoite challenge in mice. AB - Malaria caused by Plasmodium falciparum kills nearly one million children each year and imposes crippling economic burdens on families and nations worldwide. No licensed vaccine exists, but infection can be prevented by antibodies against the circumsporozoite protein (CSP), the major surface protein of sporozoites, the form of the parasite injected by mosquitoes. We have used vectored immunoprophylaxis (VIP), an adeno-associated virus-based technology, to introduce preformed antibody genes encoding anti-P. falciparum CSP mAb into mice. VIP vector-transduced mice exhibited long-lived mAb expression at up to 1,200 ug/mL in serum, and up to 70% were protected from both i.v. and mosquito bite challenge with transgenic Plasmodium berghei rodent sporozoites that incorporate the P. falciparum target of the mAb in their CSP. Serum antibody levels and protection from mosquito bite challenge were dependent on the dose of the VIP vector. All individual mice expressing CSP-specific mAb 2A10 at 1 mg/mL or more were completely protected, suggesting that in this model system, exceeding that threshold results in consistent sterile protection. Our results demonstrate the potential of VIP as a path toward the elusive goal of immunization against malaria. PMID- 25114214 TI - Rare earth elements activate endocytosis in plant cells. AB - It has long been observed that rare earth elements (REEs) regulate multiple facets of plant growth and development. However, the underlying mechanisms remain largely unclear. Here, using electron microscopic autoradiography, we show the life cycle of a light REE (lanthanum) and a heavy REE (terbium) in horseradish leaf cells. Our data indicate that REEs were first anchored on the plasma membrane in the form of nanoscale particles, and then entered the cells by endocytosis. Consistently, REEs activated endocytosis in plant cells, which may be the cellular basis of REE actions in plants. Moreover, we discovered that a portion of REEs was successively released into the cytoplasm, self-assembled to form nanoscale clusters, and finally deposited in horseradish leaf cells. Taken together, our data reveal the life cycle of REEs and their cellular behaviors in plant cells, which shed light on the cellular mechanisms of REE actions in living organisms. PMID- 25114215 TI - Wnt ligand/Frizzled 2 receptor signaling regulates tube shape and branch-point formation in the lung through control of epithelial cell shape. AB - Changing the morphology of a simple epithelial tube to form a highly ramified branching network requires changes in cell behavior that lead to tissue-wide changes in organ shape. How epithelial cells in branched organs modulate their shape and behavior to promote bending and sculpting of the epithelial sheet is not well understood, and the mechanisms underlying this process remain obscure. We show that the Wnt receptor Frizzled 2 (Fzd2) is required for domain branch formation during the initial establishment of the respiratory tree. Live imaging and transcriptome analysis of lung-branching morphogenesis demonstrate that Fzd2 promotes changes in epithelial cell length and shape. These changes in cell morphology deform the developing epithelial tube to generate and maintain new domain branches. Fzd2 controls branch formation and the shape of the epithelial tube by regulating Rho signaling and by the localization of phospho-myosin light chain 2, in turn controlling the changes in the shape of epithelial cells during morphogenesis. This study demonstrates the importance of Wnt/Fzd2 signaling in promoting and maintaining changes in epithelial cell shape that affect development of a branching network. PMID- 25114217 TI - Natural selection drives the evolution of ant life cycles. AB - The genetic origin of advanced social organization has long been one of the outstanding problems of evolutionary biology. Here we present an analysis of the major steps in ant evolution, based for the first time, to our knowledge, on combined recent advances in paleontology, phylogeny, and the study of contemporary life histories. We provide evidence of the causal forces of natural selection shaping several key phenomena: (i) the relative lateness and rarity in geological time of the emergence of eusociality in ants and other animal phylads; (ii) the prevalence of monogamy at the time of evolutionary origin; and (iii) the female-biased sex allocation observed in many ant species. We argue that a clear understanding of the evolution of social insects can emerge if, in addition to relatedness-based arguments, we take into account key factors of natural history and study how natural selection acts on alleles that modify social behavior. PMID- 25114216 TI - Enhanced killing of antibiotic-resistant bacteria enabled by massively parallel combinatorial genetics. AB - New therapeutic strategies are needed to treat infections caused by drug resistant bacteria, which constitute a major growing threat to human health. Here, we use a high-throughput technology to identify combinatorial genetic perturbations that can enhance the killing of drug-resistant bacteria with antibiotic treatment. This strategy, Combinatorial Genetics En Masse (CombiGEM), enables the rapid generation of high-order barcoded combinations of genetic elements for high-throughput multiplexed characterization based on next generation sequencing. We created ~ 34,000 pairwise combinations of Escherichia coli transcription factor (TF) overexpression constructs. Using Illumina sequencing, we identified diverse perturbations in antibiotic-resistance phenotypes against carbapenem-resistant Enterobacteriaceae. Specifically, we found multiple TF combinations that potentiated antibiotic killing by up to 10(6) fold and delivered these combinations via phagemids to increase the killing of highly drug-resistant E. coli harboring New Delhi metallo-beta-lactamase-1. Moreover, we constructed libraries of three-wise combinations of transcription factors with >4 million unique members and demonstrated that these could be tracked via next-generation sequencing. We envision that CombiGEM could be extended to other model organisms, disease models, and phenotypes, where it could accelerate massively parallel combinatorial genetics studies for a broad range of biomedical and biotechnology applications, including the treatment of antibiotic resistant infections. PMID- 25114219 TI - Demography, not inheritance, drives phenotypic change in hunted bighorn sheep. AB - Selective harvest, such as trophy hunting, can shift the distribution of a quantitative character such as body size. If the targeted character is heritable, then there will be an evolutionary response to selection, and where the trait is not, then any response will be plastic or demographic. Identifying the relative contributions of these different mechanisms is a major challenge in wildlife conservation. New mathematical approaches can provide insight not previously available. Here we develop a size- and age-based two-sex integral projection model based on individual-based data from a long-term study of hunted bighorn sheep (Ovis canadensis) at Ram Mountain, Canada. We simulate the effect of trophy hunting on body size and find that the inheritance of body mass is weak and that any perceived decline in body mass of the bighorn population is largely attributable to demographic change and environmental factors. To our knowledge, this work provides the first use of two-sex integral projection models to investigate the potential eco-evolutionary consequences of selective harvest. PMID- 25114218 TI - Primary cilia are required in a unique subpopulation of neural progenitors. AB - The apical domain of embryonic (radial glia) and adult (B1 cells) neural stem cells (NSCs) contains a primary cilium. This organelle has been suggested to function as an antenna for the detection of morphogens or growth factors. In particular, primary cilia are essential for Hedgehog (Hh) signaling, which plays key roles in brain development. Their unique location facing the ventricular lumen suggests that primary cilia in NSCs could play an important role in reception of signals within the cerebrospinal fluid. Surprisingly, ablation of primary cilia using conditional alleles for genes essential for intraflagellar transport [kinesin family member 3A (Kif3a) and intraflagellar transport 88 (Ift88)] and Cre drivers that are activated at early [Nestin; embryonic day 10.5 (E10.5)] and late [human glial fibrillary acidic protein (hGFAP); E13.5] stages of mouse neural development resulted in no apparent developmental defects. Neurogenesis in the ventricular-subventricular zone (V-SVZ) shortly after birth was also largely unaffected, except for a restricted ventral domain previously known to be regulated by Hh signaling. However, Kif3a and Ift88 genetic ablation also disrupts ependymal cilia, resulting in hydrocephalus by postnatal day 4. To directly study the role of B1 cells' primary cilia without the confounding effects of hydrocephalus, we stereotaxically targeted elimination of Kif3a from a subpopulation of radial glia, which resulted in ablation of primary cilia in a subset of B1 cells. Again, this experiment resulted in decreased neurogenesis only in the ventral V-SVZ. Primary cilia ablation led to disruption of Hh signaling in this subdomain. We conclude that primary cilia are required in a specific Hh-regulated subregion of the postnatal V-SVZ. PMID- 25114220 TI - Autophagy protects C. elegans against necrosis during Pseudomonas aeruginosa infection. AB - Autophagy, a conserved pathway that delivers intracellular materials into lysosomes for degradation, is involved in development, aging, and a variety of diseases. Accumulating evidence demonstrates that autophagy plays a protective role against infectious diseases by diminishing intracellular pathogens, including bacteria, viruses, and parasites. However, the mechanism by which autophagy regulates innate immunity remains largely unknown. Here, we show that autophagy is involved in host defense against a pathogenic bacterium Pseudomonas aeruginosa in the metazoan Caenorhabditis elegans. P. aeruginosa infection induces autophagy via a conserved extracellular signal-regulated kinase (ERK). Intriguingly, impairment of autophagy does not influence the intestinal accumulation of P. aeruginosa, but instead induces intestinal necrosis. Inhibition of necrosis results in the survival of autophagy-deficient worms after P. aeruginosa infection. These findings reveal a previously unidentified role for autophagy in protection against necrosis triggered by pathogenic bacteria in C. elegans and implicate that such a function of autophagy may be conserved through the inflammatory response in diverse organisms. PMID- 25114221 TI - Inhibitor of MYC identified in a Krohnke pyridine library. AB - In a fluorescence polarization screen for the MYC-MAX interaction, we have identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Krohnke pyridine library. The Kd of KJ-Pyr-9 for MYC in vitro is 6.5 +/- 1.0 nM, as determined by backscattering interferometry; KJ-Pyr-9 also interferes with MYC MAX complex formation in the cell, as shown in a protein fragment complementation assay. KJ-Pyr-9 specifically inhibits MYC-induced oncogenic transformation in cell culture; it has no or only weak effects on the oncogenic activity of several unrelated oncoproteins. KJ-Pyr-9 preferentially interferes with the proliferation of MYC-overexpressing human and avian cells and specifically reduces the MYC driven transcriptional signature. In vivo, KJ-Pyr-9 effectively blocks the growth of a xenotransplant of MYC-amplified human cancer cells. PMID- 25114222 TI - Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia-cell cycle dual reporter. AB - Although aerobic glycolysis provides an advantage in the hypoxic tumor microenvironment, some cancer cells can also respire via oxidative phosphorylation. These respiring ("non-Warburg") cells were previously thought not to play a key role in tumorigenesis and thus fell from favor in the literature. We sought to determine whether subpopulations of hypoxic cancer cells have different metabolic phenotypes and gene-expression profiles that could influence tumorigenicity and therapeutic response, and we therefore developed a dual fluorescent protein reporter, HypoxCR, that detects hypoxic [hypoxia inducible factor (HIF) active] and/or cycling cells. Using HEK293T cells as a model, we identified four distinct hypoxic cell populations by flow cytometry. The non-HIF/noncycling cell population expressed a unique set of genes involved in mitochondrial function. Relative to the other subpopulations, these hypoxic "non-Warburg" cells had highest oxygen consumption rates and mitochondrial capacity consistent with increased mitochondrial respiration. We found that these respiring cells were unexpectedly tumorigenic, suggesting that continued respiration under limiting oxygen conditions may be required for tumorigenicity. PMID- 25114224 TI - Predicting hybrid performance in rice using genomic best linear unbiased prediction. AB - Genomic selection is an upgrading form of marker-assisted selection for quantitative traits, and it differs from the traditional marker-assisted selection in that markers in the entire genome are used to predict genetic values and the QTL detection step is skipped. Genomic selection holds the promise to be more efficient than the traditional marker-assisted selection for traits controlled by polygenes. Genomic selection for pure breed improvement is based on marker information and thus leads to cost-saving due to early selection before phenotypes are measured. When applied to hybrid breeding, genomic selection is anticipated to be even more efficient because genotypes of hybrids are predetermined by their inbred parents. Hybrid breeding has been an important tool to increase crop productivity. Here we proposed and applied an advanced method to predict hybrid performance, in which a subset of all potential hybrids is used as a training sample to predict trait values of all potential hybrids. The method is called genomic best linear unbiased prediction. The technology applied to hybrids is called genomic hybrid breeding. We used 278 randomly selected hybrids derived from 210 recombinant inbred lines of rice as a training sample and predicted all 21,945 potential hybrids. The average yield of top 100 selection shows a 16% increase compared with the average yield of all potential hybrids. The new strategy of marker-guided prediction of hybrid yields serves as a proof of concept for a new technology that may potentially revolutionize hybrid breeding. PMID- 25114225 TI - Drought stress variability in ancient Near Eastern agricultural systems evidenced by delta13C in barley grain. AB - The collapse and resilience of political systems in the ancient Near East and their relationship with agricultural development have been of wide interest in archaeology and anthropology. Despite attempts to link the archaeological evidence to local paleoclimate data, the precise role of environmental conditions in ancient agricultural production remains poorly understood. Recently, stable isotope analysis has been used for reconstructing site-specific ancient growing conditions for crop species in semiarid and arid landscapes. To open the discussion of the role of regional diversity in past agricultural production as a factor in societal development, we present 1.037 new stable carbon isotope measurements from 33 archaeological sites and modern fields in the geographic area of the Fertile Crescent, spanning the Aceramic Neolithic [10,000 calibrated years (cal) B.C.] to the later Iron Age (500 cal B.C.), alongside modern data from 13 locations. Our data show that drought stress was an issue in many agricultural settlements in the ancient Near East, particularly in correlation with the major Holocene climatic fluctuations, but its regional impact was diverse and influenced by geographic factors. Although cereals growing in the coastal areas of the northern Levant were relatively unaffected by Holocene climatic fluctuations, farmers of regions further inland had to apply irrigation to cope with increased water stress. However, inland agricultural strategies showed a high degree of variability. Our findings suggest that regional differences in climatic effects led to diversified strategies in ancient subsistence and economy even within spatially limited cultural units. PMID- 25114223 TI - Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells. AB - Genetic alterations that reduce the function of the immunoregulatory cytokine IL 10 contribute to colitis in mouse and man. Myeloid cells such as macrophages (MPhis) and dendritic cells (DCs) play an essential role in determining the relative abundance of IL-10 versus inflammatory cytokines in the gut. As such, using small molecules to boost IL-10 production by DCs-MPhis represents a promising approach to increase levels of this cytokine specifically in gut tissues. Toward this end, we screened a library of well-annotated kinase inhibitors for compounds that enhance production of IL-10 by murine bone-marrow derived DCs stimulated with the yeast cell wall preparation zymosan. This approach identified a number of kinase inhibitors that robustly up-regulate IL-10 production including the Food and Drug Administration (FDA)-approved drugs dasatinib, bosutinib, and saracatinib that target ABL, SRC-family, and numerous other kinases. Correlating the kinase selectivity profiles of the active compounds with their effect on IL-10 production suggests that inhibition of salt inducible kinases (SIKs) mediates the observed IL-10 increase. This was confirmed using the SIK-targeting inhibitor HG-9-91-01 and a series of structural analogs. The stimulatory effect of SIK inhibition on IL-10 is also associated with decreased production of the proinflammatory cytokines IL-1beta, IL-6, IL-12, and TNF-alpha, and these coordinated effects are observed in human DCs-MPhis and anti inflammatory CD11c(+) CX3CR1(hi) cells isolated from murine gut tissue. Collectively, these studies demonstrate that SIK inhibition promotes an anti inflammatory phenotype in activated myeloid cells marked by robust IL-10 production and establish these effects as a previously unidentified activity associated with several FDA-approved multikinase inhibitors. PMID- 25114226 TI - MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma. AB - Glioblastomas (GBMs) diffusely infiltrate the brain, making complete removal by surgical resection impossible. The mixture of neoplastic and nonneoplastic cells that remain after surgery form the biological context for adjuvant therapeutic intervention and recurrence. We performed RNA-sequencing (RNA-seq) and histological analysis on radiographically guided biopsies taken from different regions of GBM and showed that the tissue contained within the contrast-enhancing (CE) core of tumors have different cellular and molecular compositions compared with tissue from the nonenhancing (NE) margins of tumors. Comparisons with the The Cancer Genome Atlas dataset showed that the samples from CE regions resembled the proneural, classical, or mesenchymal subtypes of GBM, whereas the samples from the NE regions predominantly resembled the neural subtype. Computational deconvolution of the RNA-seq data revealed that contributions from nonneoplastic brain cells significantly influence the expression pattern in the NE samples. Gene ontology analysis showed that the cell type-specific expression patterns were functionally distinct and highly enriched in genes associated with the corresponding cell phenotypes. Comparing the RNA-seq data from the GBM samples to that of nonneoplastic brain revealed that the differentially expressed genes are distributed across multiple cell types. Notably, the patterns of cell type specific alterations varied between the different GBM subtypes: the NE regions of proneural tumors were enriched in oligodendrocyte progenitor genes, whereas the NE regions of mesenchymal GBM were enriched in astrocytic and microglial genes. These subtype-specific patterns provide new insights into molecular and cellular composition of the infiltrative margins of GBM. PMID- 25114228 TI - Synchronization in human musical rhythms and mutually interacting complex systems. AB - Though the music produced by an ensemble is influenced by multiple factors, including musical genre, musician skill, and individual interpretation, rhythmic synchronization is at the foundation of musical interaction. Here, we study the statistical nature of the mutual interaction between two humans synchronizing rhythms. We find that the interbeat intervals of both laypeople and professional musicians exhibit scale-free (power law) cross-correlations. Surprisingly, the next beat to be played by one person is dependent on the entire history of the other person's interbeat intervals on timescales up to several minutes. To understand this finding, we propose a general stochastic model for mutually interacting complex systems, which suggests a physiologically motivated explanation for the occurrence of scale-free cross-correlations. We show that the observed long-term memory phenomenon in rhythmic synchronization can be imitated by fractal coupling of separately recorded or synthesized audio tracks and thus applied in electronic music. Though this study provides an understanding of fundamental characteristics of timing and synchronization at the interbrain level, the mutually interacting complex systems model may also be applied to study the dynamics of other complex systems where scale-free cross-correlations have been observed, including econophysics, physiological time series, and collective behavior of animal flocks. PMID- 25114227 TI - Nicotinic and muscarinic agonists and acetylcholinesterase inhibitors stimulate a common pathway to enhance GluN2B-NMDAR responses. AB - Nicotinic and muscarinic ACh receptor agonists and acetylcholinesterase inhibitors (AChEIs) can enhance cognitive function. However, it is unknown whether a common signaling pathway is involved in the effect. Here, we show that in vivo administration of nicotine, AChEIs, and an m1 muscarinic (m1) agonist increase glutamate receptor, ionotropic, N-methyl D-aspartate 2B (GluN2B) containing NMDA receptor (NR2B-NMDAR) responses, a necessary component in memory formation, in hippocampal CA1 pyramidal cells, and that coadministration of the m1 antagonist pirenzepine prevents the effect of cholinergic drugs. These observations suggest that the effect of nicotine is secondary to increased release of ACh via the activation of nicotinic ACh receptors (nAChRs) and involves m1 receptor activation through ACh. In vitro activation of m1 receptors causes the selective enhancement of NR2B-NMDAR responses in CA1 pyramidal cells, and in vivo exposure to cholinergic drugs occludes the in vitro effect. Furthermore, in vivo exposure to cholinergic drugs suppresses the potentiating effect of Src on NMDAR responses in vitro. These results suggest that exposure to cholinergic drugs maximally stimulates the m1/guanine nucleotide-binding protein subunit alpha q/PKC/proline-rich tyrosine kinase 2/Src signaling pathway for the potentiation of NMDAR responses in vivo, occluding the in vitro effects of m1 activation and Src. Thus, our results indicate not only that nAChRs, ACh, and m1 receptors are on the same pathway involving Src signaling but also that NR2B NMDARs are a point of convergence of cholinergic and glutamatergic pathways involved in learning and memory. PMID- 25114229 TI - Profile of Alexander D. Johnson. PMID- 25114231 TI - Single-shot stand-off chemical identification of powders using random Raman lasing. AB - The task of identifying explosives, hazardous chemicals, and biological materials from a safe distance is the subject we consider. Much of the prior work on stand off spectroscopy using light has been devoted to generating a backward propagating beam of light that can be used drive further spectroscopic processes. The discovery of random lasing and, more recently, random Raman lasing provide a mechanism for remotely generating copious amounts of chemically specific Raman scattered light. The bright nature of random Raman lasing renders directionality unnecessary, allowing for the detection and identification of chemicals from large distances in real time. In this article, the single-shot remote identification of chemicals at kilometer-scale distances is experimentally demonstrated using random Raman lasing. PMID- 25114230 TI - Interleukin-1 deficiency prolongs ovarian lifespan in mice. AB - Oocyte endowment dwindles away during prepubertal and adult life until menopause occurs, and apoptosis has been identified as a central mechanism responsible for oocyte elimination. A few recent reports suggest that uncontrolled inflammation may adversely affect ovarian reserve. We tested the possible role of the proinflammatory cytokine IL-1 in the age-related exhaustion of ovarian reserve using IL-1alpha and IL-1beta-KO mice. IL-1alpha-KO mice showed a substantially higher pregnancy rate and litter size compared with WT mice at advanced age. The number of secondary and antral follicles was significantly higher in 2.5-mo-old IL-1alpha-KO ovaries compared with WT ovaries. Serum anti-Mullerian hormone, a putative marker of ovarian reserve, was markedly higher in IL-1alpha-KO mice from 2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1beta KO mice displayed a comparable but more subtle prolongation of ovarian lifespan compared with IL-1alpha-KO mice. The protein and mRNA of both IL-1alpha and IL 1beta mice were localized within the developing follicles (oocytes and granulosa cells), and their ovarian mRNA levels increased with age. Molecular analysis revealed decreased apoptotic signaling [higher B-cell lymphoma 2 (BCL-2) and lower BCL-2-associated X protein levels], along with a marked attenuation in the expression of genes coding for the proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha in ovaries of IL-1alpha-KO mice compared with WT mice. Taken together, IL-1 emerges as an important participant in the age-related exhaustion of ovarian reserve in mice, possibly by enhancing the expression of inflammatory genes and promoting apoptotic pathways. PMID- 25114232 TI - EFA6 controls Arf1 and Arf6 activation through a negative feedback loop. AB - Guanine nucleotide exchange factors (GEFs) of the exchange factor for Arf6 (EFA6), brefeldin A-resistant Arf guanine nucleotide exchange factor (BRAG), and cytohesin subfamilies activate small GTPases of the Arf family in endocytic events. These ArfGEFs carry a pleckstrin homology (PH) domain in tandem with their catalytic Sec7 domain, which is autoinhibitory and supports a positive feedback loop in cytohesins but not in BRAGs, and has an as-yet unknown role in EFA6 regulation. In this study, we analyzed how EFA6A is regulated by its PH and C terminus (Ct) domains by reconstituting its GDP/GTP exchange activity on membranes. We found that EFA6 has a previously unappreciated high efficiency toward Arf1 on membranes and that, similar to BRAGs, its PH domain is not autoinhibitory and strongly potentiates nucleotide exchange on anionic liposomes. However, in striking contrast to both cytohesins and BRAGs, EFA6 is regulated by a negative feedback loop, which is mediated by an allosteric interaction of Arf6 GTP with the PH-Ct domain of EFA6 and monitors the activation of Arf1 and Arf6 differentially. These observations reveal that EFA6, BRAG, and cytohesins have unanticipated commonalities associated with divergent regulatory regimes. An important implication is that EFA6 and cytohesins may combine in a mixed negative positive feedback loop. By allowing EFA6 to sustain a pool of dormant Arf6-GTP, such a circuit would fulfill the absolute requirement of cytohesins for activation by Arf-GTP before amplification of their GEF activity by their positive feedback loop. PMID- 25114233 TI - Microbial-induced meprin beta cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus. AB - The mucus that covers and protects the epithelium of the intestine is built around its major structural component, the gel-forming MUC2 mucin. The gel forming mucins have traditionally been assumed to be secreted as nonattached. The colon has a two-layered mucus system where the inner mucus is attached to the epithelium, whereas the small intestine normally has a nonattached mucus. However, the mucus of the small intestine of meprin beta-deficient mice was now found to be attached. Meprin beta is an endogenous zinc-dependent metalloprotease now shown to cleave the N-terminal region of the MUC2 mucin at two specific sites. When recombinant meprin beta was added to the attached mucus of meprin beta-deficient mice, the mucus was detached from the epithelium. Similar to meprin beta-deficient mice, germ-free mice have attached mucus as they did not shed the membrane-anchored meprin beta into the luminal mucus. The ileal mucus of cystic fibrosis (CF) mice with a nonfunctional cystic fibrosis transmembrane conductance regulator (CFTR) channel was recently shown to be attached to the epithelium. Addition of recombinant meprin beta to CF mucus did not release the mucus, but further addition of bicarbonate rendered the CF mucus normal, suggesting that MUC2 unfolding exposed the meprin beta cleavage sites. Mucus is thus secreted attached to the goblet cells and requires an enzyme, meprin beta in the small intestine, to be detached and released into the intestinal lumen. This process regulates mucus properties, can be triggered by bacterial contact, and is nonfunctional in CF due to poor mucin unfolding. PMID- 25114234 TI - Bioengineered functional brain-like cortical tissue. AB - The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury. PMID- 25114237 TI - Fair sampling perspective on an apparent violation of duality. AB - In the event in which a quantum mechanical particle can pass from an initial state to a final state along two possible paths, the duality principle states that "the simultaneous observation of wave and particle behavior is prohibited" [Scully MO, Englert B-G, Walther H (1991) Nature 351:111-116]. Whereas wave behavior is associated with the observation of interference fringes, particle behavior generally corresponds to the acquisition of which-path information by means of coupling the paths to a measuring device or part of their environment. In this paper, we show how the consequences of duality change when allowing for biased sampling, that is, postselected measurements on specific degrees of freedom of the environment of the two-path state. Our work gives insight into a possible mechanism for obtaining simultaneous high which-path information and high-visibility fringes in a single experiment. Further, our results introduce previously unidentified avenues for experimental tests of duality. PMID- 25114236 TI - Marine ammonia-oxidizing archaeal isolates display obligate mixotrophy and wide ecotypic variation. AB - Ammonia-oxidizing archaea (AOA) are now implicated in exerting significant control over the form and availability of reactive nitrogen species in marine environments. Detailed studies of specific metabolic traits and physicochemical factors controlling their activities and distribution have not been well constrained in part due to the scarcity of isolated AOA strains. Here, we report the isolation of two new coastal marine AOA, strains PS0 and HCA1. Comparison of the new strains to Nitrosopumilus maritimus strain SCM1, the only marine AOA in pure culture thus far, demonstrated distinct adaptations to pH, salinity, organic carbon, temperature, and light. Strain PS0 sustained nearly 80% of ammonia oxidation activity at a pH as low as 5.9, indicating that coastal strains may be less sensitive to the ongoing reduction in ocean pH. Notably, the two novel isolates are obligate mixotrophs that rely on uptake and assimilation of organic carbon compounds, suggesting a direct coupling between chemolithotrophy and organic matter assimilation in marine food webs. All three isolates showed only minor photoinhibition at 15 uE ? m(-2) ? s(-1) and rapid recovery of ammonia oxidation in the dark, consistent with an AOA contribution to the primary nitrite maximum and the plausibility of a diurnal cycle of archaeal ammonia oxidation activity in the euphotic zone. Together, these findings highlight an unexpected adaptive capacity within closely related marine group I Archaea and provide new understanding of the physiological basis of the remarkable ecological success reflected by their generally high abundance in marine environments. PMID- 25114235 TI - Small RNA combination therapy for lung cancer. AB - MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but their effective delivery to most solid tumors has been difficult. Here, we show that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically engineered mouse model of lung cancer based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a levels in lung tumors, specifically down-regulated miR-34a target genes, and slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene expression and MAPK signaling, increased apoptosis, and inhibited tumor growth. The combination of miR-34a and siRNA targeting Kras improved therapeutic responses over those observed with either small RNA alone, leading to tumor regression. Furthermore, nanoparticle-mediated small RNA delivery plus conventional, cisplatin-based chemotherapy prolonged survival in this model compared with chemotherapy alone. These findings demonstrate that RNA combination therapy is possible in an autochthonous model of lung cancer and provide preclinical support for the use of small RNA therapies in patients who have cancer. PMID- 25114238 TI - Collective credit allocation in science. AB - Collaboration among researchers is an essential component of the modern scientific enterprise, playing a particularly important role in multidisciplinary research. However, we continue to wrestle with allocating credit to the coauthors of publications with multiple authors, because the relative contribution of each author is difficult to determine. At the same time, the scientific community runs an informal field-dependent credit allocation process that assigns credit in a collective fashion to each work. Here we develop a credit allocation algorithm that captures the coauthors' contribution to a publication as perceived by the scientific community, reproducing the informal collective credit allocation of science. We validate the method by identifying the authors of Nobel-winning papers that are credited for the discovery, independent of their positions in the author list. The method can also compare the relative impact of researchers working in the same field, even if they did not publish together. The ability to accurately measure the relative credit of researchers could affect many aspects of credit allocation in science, potentially impacting hiring, funding, and promotion decisions. PMID- 25114239 TI - Hybrid biosynthetic gene therapy vector development and dual engineering capacity. AB - Genetic vaccines offer a treatment opportunity based upon successful gene delivery to specific immune cell modulators. Driving the process is the vector chosen for gene cargo packaging and subsequent delivery to antigen-presenting cells (APCs) capable of triggering an immune cascade. As such, the delivery process must successfully navigate a series of requirements and obstacles associated with the chosen vector and target cell. In this work, we present the development and assessment of a hybrid gene delivery vector containing biological and biomaterial components. Each component was chosen to design and engineer gene delivery separately in a complimentary and fundamentally distinct fashion. A bacterial (Escherichia coli) inner core and a biomaterial [poly(beta-amino ester)]-coated outer surface allowed the simultaneous application of molecular biology and polymer chemistry to address barriers associated with APC gene delivery, which include cellular uptake and internalization, phagosomal escape, and intracellular cargo concentration. The approach combined and synergized normally disparate vector properties and tools, resulting in increased in vitro gene delivery beyond individual vector components or commercially available transfection agents. Furthermore, the hybrid device demonstrated a strong, efficient, and safe in vivo humoral immune response compared with traditional forms of antigen delivery. In summary, the flexibility, diversity, and potential of the hybrid design were developed and featured in this work as a platform for multivariate engineering at the vector and cellular scales for new applications in gene delivery immunotherapy. PMID- 25114240 TI - A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs. AB - The recent success of antibody-drug conjugates (ADCs) in the treatment of cancer has led to a revived interest in microtubule-destabilizing agents. Here, we determined the high-resolution crystal structure of the complex between tubulin and maytansine, which is part of an ADC that is approved by the US Food and Drug Administration (FDA) for the treatment of advanced breast cancer. We found that the drug binds to a site on beta-tubulin that is distinct from the vinca domain and that blocks the formation of longitudinal tubulin interactions in microtubules. We also solved crystal structures of tubulin in complex with both a variant of rhizoxin and the phase 1 drug PM060184. Consistent with biochemical and mutagenesis data, we found that the two compounds bound to the same site as maytansine and that the structures revealed a common pharmacophore for the three ligands. Our results delineate a distinct molecular mechanism of action for the inhibition of microtubule assembly by clinically relevant agents. They further provide a structural basis for the rational design of potent microtubule destabilizing agents, thus opening opportunities for the development of next generation ADCs for the treatment of cancer. PMID- 25114241 TI - Nucleoprotein architectures regulating the directionality of viral integration and excision. AB - The virally encoded site-specific recombinase Int collaborates with its accessory DNA bending proteins IHF, Xis, and Fis to assemble two distinct, very large, nucleoprotein complexes that carry out either integrative or excisive recombination along regulated and essentially unidirectional pathways. The core of each complex consists of a tetramer of Integrase protein (Int), which is a heterobivalent DNA binding protein that binds and bridges a core-type DNA site (where strand cleavage and ligation are executed), and a distal arm-type site, that is brought within range by one or more DNA bending proteins. The recent determination of the patterns of these Int bridges has made it possible to think realistically about the global architecture of the recombinogenic complexes. Here, we combined the previously determined Int bridging patterns with in-gel FRET experiments and in silico modeling to characterize and differentiate the two 400-kDa multiprotein Holiday junction recombination intermediates formed during lambda integration and excision. The results lead to architectural models that explain how integration and excision are regulated in lambda site-specific recombination. Our confidence in the basic features of these architectures is based on the redundancy and self-consistency of the underlying data from two very different experimental approaches to establish bridging interactions, a set of strategic intracomplex distances from FRET experiments, and the model's ability to explain key aspects of the integrative and excisive recombination pathways, such as topological changes, the mechanism of capturing attB, and the features of asymmetry and flexibility within the complexes. PMID- 25114242 TI - Coevolutionary information, protein folding landscapes, and the thermodynamics of natural selection. AB - The energy landscape used by nature over evolutionary timescales to select protein sequences is essentially the same as the one that folds these sequences into functioning proteins, sometimes in microseconds. We show that genomic data, physical coarse-grained free energy functions, and family-specific information theoretic models can be combined to give consistent estimates of energy landscape characteristics of natural proteins. One such characteristic is the effective temperature T(sel) at which these foldable sequences have been selected in sequence space by evolution. T(sel) quantifies the importance of folded-state energetics and structural specificity for molecular evolution. Across all protein families studied, our estimates for T(sel) are well below the experimental folding temperatures, indicating that the energy landscapes of natural foldable proteins are strongly funneled toward the native state. PMID- 25114244 TI - Dopamine challenge reveals neuroadaptive changes in marijuana abusers. PMID- 25114245 TI - Quasi-resonant circulation regimes and hemispheric synchronization of extreme weather in boreal summer. AB - The recent decade has seen an exceptional number of high-impact summer extremes in the Northern Hemisphere midlatitudes. Many of these events were associated with anomalous jet stream circulation patterns characterized by persistent high amplitude quasi-stationary Rossby waves. Two mechanisms have recently been proposed that could provoke such patterns: (i) a weakening of the zonal mean jets and (ii) an amplification of quasi-stationary waves by resonance between free and forced waves in midlatitude waveguides. Based upon spectral analysis of the midtroposphere wind field, we show that the persistent jet stream patterns were, in the first place, due to an amplification of quasi-stationary waves with zonal wave numbers 6-8. However, we also detect a weakening of the zonal mean jet during these events; thus both mechanisms appear to be important. Furthermore, we demonstrate that the anomalous circulation regimes lead to persistent surface weather conditions and therefore to midlatitude synchronization of extreme heat and rainfall events on monthly timescales. The recent cluster of resonance events has resulted in a statistically significant increase in the frequency of high amplitude quasi-stationary waves of wave numbers 7 and 8 in July and August. We show that this is a robust finding that holds for different pressure levels and reanalysis products. We argue that recent rapid warming in the Arctic and associated changes in the zonal mean zonal wind have created favorable conditions for double jet formation in the extratropics, which promotes the development of resonant flow regimes. PMID- 25114243 TI - Structural basis for the recruitment and activation of the Legionella phospholipase VipD by the host GTPase Rab5. AB - A challenge for microbial pathogens is to assure that their translocated effector proteins target only the correct host cell compartment during infection. The Legionella pneumophila effector vacuolar protein sorting inhibitor protein D (VipD) localizes to early endosomal membranes and alters their lipid and protein composition, thereby protecting the pathogen from endosomal fusion. This process requires the phospholipase A1 (PLA1) activity of VipD that is triggered specifically on VipD binding to the host cell GTPase Rab5, a key regulator of endosomes. Here, we present the crystal structure of VipD in complex with constitutively active Rab5 and reveal the molecular mechanism underlying PLA1 activation. An active site-obstructing loop that originates from the C-terminal domain of VipD is repositioned on Rab5 binding, thereby exposing the catalytic pocket within the N-terminal PLA1 domain. Substitution of amino acid residues located within the VipD-Rab5 interface prevented Rab5 binding and PLA1 activation and caused a failure of VipD mutant proteins to target to Rab5-enriched endosomal structures within cells. Experimental and computational analyses confirmed an extended VipD-binding interface on Rab5, explaining why this L. pneumophila effector can compete with cellular ligands for Rab5 binding. Together, our data explain how the catalytic activity of a microbial effector can be precisely linked to its subcellular localization. PMID- 25114246 TI - A cellular solution to an information-processing problem. AB - Signaling receptors on the cell surface are mobile and have evolved to efficiently sense and process mechanical or chemical information. We pose the problem of identifying the optimal strategy for placing a collection of distributed and mobile sensors to faithfully estimate a signal that varies in space and time. The optimal strategy has to balance two opposing objectives: the need to locally assemble sensors to reduce estimation noise and the need to spread them to reduce spatial error. This results in a phase transition in the space of strategies as a function of sensor density and efficiency. We show that these optimal strategies have been arrived at multiple times in diverse cell biology contexts, including the stationary lattice architecture of receptors on the bacterial cell surface and the active clustering of cell-surface signaling receptors in metazoan cells. PMID- 25114247 TI - Mapping the lambda Integrase bridges in the nucleoprotein Holliday junction intermediates of viral integrative and excisive recombination. AB - The site-specific recombinase encoded by bacteriophage lambda [lambda Integrase (Int)] is responsible for integrating and excising the viral chromosome into and out of the chromosome of its Escherichia coli host. In contrast to the other well studied and highly exploited tyrosine recombinase family members, such as Cre and Flp, Int carries out a reaction that is highly directional, tightly regulated, and depends on an ensemble of accessory DNA bending proteins acting on 240 bp of DNA encoding 16 protein binding sites. This additional complexity enables two pathways, integrative and excisive recombination, whose opposite, and effectively irreversible, directions are dictated by different physiological and environmental signals. Int recombinase is a heterobivalent DNA binding protein that binds via its small amino-terminal domain to high affinity arm-type DNA sites and via its large, compound carboxyl-terminal domain to core-type DNA sites, where DNA cleavage and ligation are executed. Each of the four Int protomers, within a multiprotein 400-kDa recombinogenic complex, is thought to bind and, with the aid of DNA bending proteins, bridge one arm- and one core-type DNA site. Despite a wealth of genetic, biochemical, and functional information generated by many laboratories over the last 50 y, it has not been possible to decipher the patterns of Int bridges, an essential step in understanding the architectures responsible for regulated directionality of recombination. We used site-directed chemical cross-linking of Int in trapped Holliday junction recombination intermediates and recombination reactions with chimeric recombinases, to identify the unique and monogamous patterns of Int bridges for integrative and excisive recombination. PMID- 25114249 TI - Electron spin changes during general anesthesia in Drosophila. AB - We show that the general anesthetics xenon, sulfur hexafluoride, nitrous oxide, and chloroform cause rapid increases of different magnitude and time course in the electron spin content of Drosophila. With the exception of CHCl3, these changes are reversible. Anesthetic-resistant mutant strains of Drosophila exhibit a different pattern of spin responses to anesthetic. In two such mutants, the spin response to CHCl3 is absent. We propose that these spin changes are caused by perturbation of the electronic structure of proteins by general anesthetics. Using density functional theory, we show that general anesthetics perturb and extend the highest occupied molecular orbital of a nine-residue alpha-helix. The calculated perturbations are qualitatively in accord with the Meyer-Overton relationship and some of its exceptions. We conclude that there may be a connection between spin, electron currents in cells, and the functioning of the nervous system. PMID- 25114248 TI - Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma. AB - Remnants of ancient transposable elements (TEs) are abundant in mammalian genomes. These sequences harbor multiple regulatory motifs and hence are capable of influencing expression of host genes. In response to environmental changes, TEs are known to be released from epigenetic repression and to become transcriptionally active. Such activation could also lead to lineage inappropriate activation of oncogenes, as one study described in Hodgkin lymphoma. However, little further evidence for this mechanism in other cancers has been reported. Here, we reanalyzed whole transcriptome data from a large cohort of patients with diffuse large B-cell lymphoma (DLBCL) compared with normal B-cell centroblasts to detect genes ectopically expressed through activation of TE promoters. We have identified 98 such TE-gene chimeric transcripts that were exclusively expressed in primary DLBCL cases and confirmed several in DLBCL-derived cell lines. We further characterized a TE-gene chimeric transcript involving a fatty acid-binding protein gene (LTR2-FABP7), normally expressed in brain, that was ectopically expressed in a subset of DLBCL patients through the use of an endogenous retroviral LTR promoter of the LTR2 family. The LTR2-FABP7 chimeric transcript encodes a novel chimeric isoform of the protein with characteristics distinct from native FABP7. In vitro studies reveal a dependency for DLBCL cell line proliferation and growth on LTR2-FABP7 chimeric protein expression. Taken together, these data demonstrate the significance of TEs as regulators of aberrant gene expression in cancer and suggest that LTR2 FABP7 may contribute to the pathogenesis of DLBCL in a subgroup of patients. PMID- 25114250 TI - Chaperone-enhanced purification of unconventional myosin 15, a molecular motor specialized for stereocilia protein trafficking. AB - Unconventional myosin 15 is a molecular motor expressed in inner ear hair cells that transports protein cargos within developing mechanosensory stereocilia. Mutations of myosin 15 cause profound hearing loss in humans and mice; however, the properties of this motor and its regulation within the stereocilia organelle are unknown. To address these questions, we expressed a subfragment 1-like (S1) truncation of mouse myosin 15, comprising the predicted motor domain plus three light-chain binding sites. Following unsuccessful attempts to express functional myosin 15-S1 using the Spodoptera frugiperda (Sf9)-baculovirus system, we discovered that coexpression of the muscle-myosin-specific chaperone UNC45B, in addition to the chaperone heat-shock protein 90 (HSP90) significantly increased the yield of functional protein. Surprisingly, myosin 15-S1 did not bind calmodulin with high affinity. Instead, the IQ domains bound essential and regulatory light chains that are normally associated with class II myosins. We show that myosin 15-S1 is a barbed-end-directed motor that moves actin filaments in a gliding assay (~ 430 nm . s(-1) at 30 degrees C), using a power stroke of 7.9 nm. The maximum ATPase rate (k(cat) ~ 6 s(-1)) was similar to the actin detachment rate (k(det) = 6.2 s(-1)) determined in single molecule optical trapping experiments, indicating that myosin 15-S1 was rate limited by transit through strongly actin-bound states, similar to other processive myosin motors. Our data further indicate that in addition to folding muscle myosin, UNC45B facilitates maturation of an unconventional myosin. We speculate that chaperone coexpression may be a simple method to optimize the purification of other myosin motors from Sf9 insect cells. PMID- 25114251 TI - DELAY OF GERMINATION 1 mediates a conserved coat-dormancy mechanism for the temperature- and gibberellin-dependent control of seed germination. AB - Seed germination is an important life-cycle transition because it determines subsequent plant survival and reproductive success. To detect optimal spatiotemporal conditions for germination, seeds act as sophisticated environmental sensors integrating information such as ambient temperature. Here we show that the delay of germination 1 (DOG1) gene, known for providing dormancy adaptation to distinct environments, determines the optimal temperature for seed germination. By reciprocal gene-swapping experiments between Brassicaceae species we show that the DOG1-mediated dormancy mechanism is conserved. Biomechanical analyses show that this mechanism regulates the material properties of the endosperm, a seed tissue layer acting as germination barrier to control coat dormancy. We found that DOG1 inhibits the expression of gibberellin (GA) regulated genes encoding cell-wall remodeling proteins in a temperature-dependent manner. Furthermore we demonstrate that DOG1 causes temperature-dependent alterations in the seed GA metabolism. These alterations in hormone metabolism are brought about by the temperature-dependent differential expression of genes encoding key enzymes of the GA biosynthetic pathway. These effects of DOG1 lead to a temperature-dependent control of endosperm weakening and determine the optimal temperature for germination. The conserved DOG1-mediated coat-dormancy mechanism provides a highly adaptable temperature-sensing mechanism to control the timing of germination. PMID- 25114253 TI - The Holocene temperature conundrum. AB - A recent temperature reconstruction of global annual temperature shows Early Holocene warmth followed by a cooling trend through the Middle to Late Holocene [Marcott SA, et al., 2013, Science 339(6124):1198-1201]. This global cooling is puzzling because it is opposite from the expected and simulated global warming trend due to the retreating ice sheets and rising atmospheric greenhouse gases. Our critical reexamination of this contradiction between the reconstructed cooling and the simulated warming points to potentially significant biases in both the seasonality of the proxy reconstruction and the climate sensitivity of current climate models. PMID- 25114254 TI - Global agriculture and carbon trade-offs. AB - Feeding a growing and increasingly affluent world will require expanded agricultural production, which may require converting grasslands and forests into cropland. Such conversions can reduce carbon storage, habitat provision, and other ecosystem services, presenting difficult societal trade-offs. In this paper, we use spatially explicit data on agricultural productivity and carbon storage in a global analysis to find where agricultural extensification should occur to meet growing demand while minimizing carbon emissions from land use change. Selective extensification saves ~ 6 billion metric tons of carbon compared with a business-as-usual approach, with a value of approximately $1 trillion (2012 US dollars) using recent estimates of the social cost of carbon. This type of spatially explicit geospatial analysis can be expanded to include other ecosystem services and other industries to analyze how to minimize conflicts between economic development and environmental sustainability. PMID- 25114252 TI - Native microbiome impedes vertical transmission of Wolbachia in Anopheles mosquitoes. AB - Over evolutionary time, Wolbachia has been repeatedly transferred between host species contributing to the widespread distribution of the symbiont in arthropods. For novel infections to be maintained, Wolbachia must infect the female germ line after being acquired by horizontal transfer. Although mechanistic examples of horizontal transfer exist, there is a poor understanding of factors that lead to successful vertical maintenance of the acquired infection. Using Anopheles mosquitoes (which are naturally uninfected by Wolbachia) we demonstrate that the native mosquito microbiota is a major barrier to vertical transmission of a horizontally acquired Wolbachia infection. After injection into adult Anopheles gambiae, some strains of Wolbachia invade the germ line, but are poorly transmitted to the next generation. In Anopheles stephensi, Wolbachia infection elicited massive blood meal-induced mortality, preventing development of progeny. Manipulation of the mosquito microbiota by antibiotic treatment resulted in perfect maternal transmission at significantly elevated titers of the wAlbB Wolbachia strain in A. gambiae, and alleviated blood meal induced mortality in A. stephensi enabling production of Wolbachia-infected offspring. Microbiome analysis using high-throughput sequencing identified that the bacterium Asaia was significantly reduced by antibiotic treatment in both mosquito species. Supplementation of an antibiotic-resistant mutant of Asaia to antibiotic-treated mosquitoes completely inhibited Wolbachia transmission and partly contributed to blood meal-induced mortality. These data suggest that the components of the native mosquito microbiota can impede Wolbachia transmission in Anopheles. Incompatibility between the microbiota and Wolbachia may in part explain why some hosts are uninfected by this endosymbiont in nature. PMID- 25114255 TI - Fractal branching organizations of Ediacaran rangeomorph fronds reveal a lost Proterozoic body plan. AB - The branching morphology of Ediacaran rangeomorph fronds has no exact counterpart in other complex macroorganisms. As such, these fossils pose major questions as to growth patterns, functional morphology, modes of feeding, and adaptive optimality. Here, using parametric Lindenmayer systems, a formal model of rangeomorph morphologies reveals a fractal body plan characterized by self similar, axial, apical, alternate branching. Consequent morphological reconstruction for 11 taxa demonstrates an adaptive radiation based on 3D space filling strategies. The fractal body plan of rangeomorphs is shown to maximize surface area, consistent with diffusive nutrient uptake from the water column (osmotrophy). The enigmas of rangeomorph morphology, evolution, and extinction are resolved by the realization that they were adaptively optimized for unique ecological and geochemical conditions in the late Proterozoic. Changes in ocean conditions associated with the Cambrian explosion sealed their fate. PMID- 25114258 TI - Retraction for Schlaberg et al., XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors. PMID- 25114256 TI - The human dynamic clamp as a paradigm for social interaction. AB - Social neuroscience has called for new experimental paradigms aimed toward real time interactions. A distinctive feature of interactions is mutual information exchange: One member of a pair changes in response to the other while simultaneously producing actions that alter the other. Combining mathematical and neurophysiological methods, we introduce a paradigm called the human dynamic clamp (HDC), to directly manipulate the interaction or coupling between a human and a surrogate constructed to behave like a human. Inspired by the dynamic clamp used so productively in cellular neuroscience, the HDC allows a person to interact in real time with a virtual partner itself driven by well-established models of coordination dynamics. People coordinate hand movements with the visually observed movements of a virtual hand, the parameters of which depend on input from the subject's own movements. We demonstrate that HDC can be extended to cover a broad repertoire of human behavior, including rhythmic and discrete movements, adaptation to changes of pacing, and behavioral skill learning as specified by a virtual "teacher." We propose HDC as a general paradigm, best implemented when empirically verified theoretical or mathematical models have been developed in a particular scientific field. The HDC paradigm is powerful because it provides an opportunity to explore parameter ranges and perturbations that are not easily accessible in ordinary human interactions. The HDC not only enables to test the veracity of theoretical models, it also illuminates features that are not always apparent in real-time human social interactions and the brain correlates thereof. PMID- 25114257 TI - Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to human transmission of MERS coronavirus. AB - Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes ~ 36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5. We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikes' capability to adapt to human cells for cross species transmissions. PMID- 25114259 TI - Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2. AB - The tip link protein protocadherin 15 (PCDH15) is a central component of the mechanotransduction complex in auditory and vestibular hair cells. PCDH15 is hypothesized to relay external forces to the mechanically gated channel located near its cytoplasmic C terminus. How PCDH15 is coupled to the transduction machinery is not clear. Using a membrane-based two-hybrid screen to identify proteins that bind to PCDH15, we detected an interaction between zebrafish Pcdh15a and an N-terminal fragment of transmembrane channel-like 2a (Tmc2a). Tmc2a is an ortholog of mammalian TMC2, which along with TMC1 has been implicated in mechanotransduction in mammalian hair cells. Using the above-mentioned two hybrid assay, we found that zebrafish Tmc1 and Tmc2a can interact with the CD1 or CD3 cytoplasmic domain isoforms of Pcdh15a, and this interaction depends on the common region shared between the two Pcdh15 isoforms. Moreover, an interaction between mouse PCDH15-CD3 and TMC1 or TMC2 was observed in both yeast two-hybrid assays and coimmunoprecipitation experiments. To determine whether the Pcdh15-Tmc interaction is relevant to mechanotransduction in vivo, we overexpressed N terminal fragments of Tmc2a in zebrafish hair cells. Overexpression of the Tmc2a N terminus results in mislocalization of Pcdh15a within hair bundles, together with a significant decrease in mechanosensitive responses, suggesting that a Pcdh15a-Tmc complex is critical for mechanotransduction. Together, these results identify an evolutionarily conserved association between the fish and mouse orthologs of PCDH15 and TMC1 and TMC2, supporting the notion that TMCs are key components of the transduction complex in hair cells. PMID- 25114261 TI - Patterned progression of bacterial populations in the premature infant gut. AB - In the weeks after birth, the gut acquires a nascent microbiome, and starts its transition to bacterial population equilibrium. This early-in-life microbial population quite likely influences later-in-life host biology. However, we know little about the governance of community development: does the gut serve as a passive incubator where the first organisms randomly encountered gain entry and predominate, or is there an orderly progression of members joining the community of bacteria? We used fine interval enumeration of microbes in stools from multiple subjects to answer this question. We demonstrate via 16S rRNA gene pyrosequencing of 922 specimens from 58 subjects that the gut microbiota of premature infants residing in a tightly controlled microbial environment progresses through a choreographed succession of bacterial classes from Bacilli to Gammaproteobacteria to Clostridia, interrupted by abrupt population changes. As infants approach 33-36 wk postconceptional age (corresponding to the third to the twelfth weeks of life depending on gestational age at birth), the gut is well colonized by anaerobes. Antibiotics, vaginal vs. Caesarian birth, diet, and age of the infants when sampled influence the pace, but not the sequence, of progression. Our results suggest that in infants in a microbiologically constrained ecosphere of a neonatal intensive care unit, gut bacterial communities have an overall nonrandom assembly that is punctuated by microbial population abruptions. The possibility that the pace of this assembly depends more on host biology (chiefly gestational age at birth) than identifiable exogenous factors warrants further consideration. PMID- 25114263 TI - Targeted correction of RUNX1 mutation in FPD patient-specific induced pluripotent stem cells rescues megakaryopoietic defects. AB - Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) is an autosomal dominant disease of the hematopoietic system that is caused by heterozygous mutations in RUNX1. FPD/AML patients have a bleeding disorder characterized by thrombocytopenia with reduced platelet numbers and functions, and a tendency to develop AML. No suitable animal models exist for FPD/AML, as Runx11/2 mice and zebra fish do not develop bleeding disorders or leukemia. Here we derived induced pluripotent stem cells (iPSCs) from 2 patients in a family with FPD/AML, and found that the FPD iPSCs display defects in megakaryocytic differentiation in vitro. We corrected the RUNX1 mutation in 1 FPD iPSC line through gene targeting, which led to normalization of megakaryopoiesis of the iPSCs in culture. Our results demonstrate successful in vitro modeling of FPD with patient-specific iPSCs and confirm that RUNX1 mutations are responsible for megakaryopoietic defects in FPD patients. PMID- 25114262 TI - Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes. AB - Delineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., "PTSD like") and resilient (i.e., minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between tissue overlap (4-21%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factors were first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associated with individual differences when using the most stringent statistical threshold. Corticosterone treatment 1 h after PSS-exposure prevented anxiety and hyperarousal 7 d later in both sexes, confirming the GR involvement in the PSS behavioral response. In conclusion, genes and pathways associated with extreme differences in the traumatic stress behavioral response can be distinguished from those associated with trauma exposure. Blood-based biomarkers can predict aspects of brain signaling. GR signaling is a convergent signaling pathway, associated with trauma-related individual differences in both sexes. PMID- 25114264 TI - Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-beta. AB - The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Here we report that thymic stromal lymphopoietin (TSLP), a keratinocyte-derived cytokine involved in epithelial inflammation, cooperates with transforming growth factor (TGF)-beta for the generation of LCs. We show that primary human blood BDCA-1(+), but not BDCA-3(+), dendritic cells (DCs) stimulated with TSLP and TGF-beta harbor a typical CD1a(+)Langerin(+) LC phenotype. Electron microscopy established the presence of Birbeck granules, an intracellular organelle specific to LCs. LC differentiation was not observed from tonsil BDCA-1(+) and BDCA-3(+) subsets. TSLP + TGF-beta LCs had a mature phenotype with high surface levels of CD80, CD86, and CD40. They induced a potent CD4(+) T-helper (Th) cell expansion and differentiation into Th2 cells with increased production of tumor necrosis factor-alpha and interleukin-6 compared with CD34-derived LCs. Our findings establish a novel LC differentiation pathway from BDCA-1(+) blood DCs with potential implications in epithelial inflammation. Therapeutic targeting of TSLP may interfere with tissue LC repopulation from circulating precursors. PMID- 25114265 TI - "Pictures don't lie, seeing is believing": exploring attitudes to the introduction of pictorial warnings on cigarette packs in Ghana. AB - PURPOSE: To compare perceptions of text and pictorial warning labels on cigarette packs among Ghanaian smokers and nonsmokers and to explore their views on the introduction of pictorial warnings in Ghana. METHODS: Qualitative study involving 12 focus group discussions with 50 smokers and 35 nonsmokers aged 15 years and older in Kumasi, Ghana. Semistructured discussion guides along with visual discussant aids were used to explore the perception, acceptance, and potential use of pictorial warning labels in Ghana. RESULTS: Health warnings combining text and a picture were perceived by both smokers and nonsmokers to communicate health messages more effectively than text-only or picture-only warnings. The effect of text-only warnings was considered limited by low levels of literacy and by the common practice of single stick sales rather than sales of packs. Of the 6 health warnings tested, lung cancer, blindness, stroke, and throat/mouth cancer messages were perceived to have the most impact on smoking behavior, including uptake and quit attempts. CONCLUSIONS: Warning labels combining pictures and text have the potential to reduce smoking uptake, increase quit attempts, and reduce smoking appeal among smokers and nonsmokers in Ghana. Measures to prevent single stick sales, or to promote health messages to purchasers of single sticks, are required. PMID- 25114266 TI - Necrotizing fasciitis of the hand and wrist due to Prevotella bivia. PMID- 25114267 TI - An adjustable device to keep the thumb in opposition and prevent adduction contracture after surgery or injury. PMID- 25114268 TI - Read-back improves information transfer in simulated clinical crises. AB - BACKGROUND: Safe and effective healthcare is frustrated by failures in communication. Repeating back important information (read-back) is thought to enhance the effectiveness of communication across many industries. However, formal communication protocols are uncommon in healthcare teams. AIMS: We aimed to quantify the effect of read-back on the transfer of information between members of a healthcare team during a simulated clinical crisis. We hypothesised that reading back information provided by other team members would result in better knowledge of that information by the receiver than verbal response without read-back or no verbal response. METHOD: Postanaesthesia care unit nurses and anaesthetic assistants were given clinically relevant items of information at the start of 88 simulations. A clinical crisis prompted calling an anaesthetist, with no prior knowledge of the patient. Using video recordings of the simulations, we noted each time a piece of information was mentioned to the anaesthetist. Their response was coded as read-back, verbal response without read-back or no verbal response. RESULTS: If the anaesthetists read back the item of information, or otherwise verbally responded, they were, respectively, 8.27 (p<0.001) or 3.16 (p=0.03) times more likely to know the information compared with no verbal response. CONCLUSIONS: Our results suggest that training healthcare teams to use read-back techniques could increase information transfer between team members with the potential for improved patient safety. More work is needed to confirm these findings. PMID- 25114269 TI - Biomarkers of susceptibility to chemical carcinogens: the example of non-Hodgkin lymphomas. AB - BACKGROUND: Genetic susceptibly to suspected chemical and environmental carcinogens may modify the response to exposure. The aim of this review was to explore the issues involved in the study of gene-environment interactions, and to consider the use of susceptibility biomarkers in cancer epidemiology, using non Hodgkin lymphoma (NHL) as an example. SOURCES OF DATA: PubMed, EMBASE and Web of Science were searched for peer-reviewed articles considering biomarkers of susceptibility to chemical, agricultural and industrial carcinogens in the aetiology of NHL. AREAS OF AGREEMENT: The results suggest a modifying role for genetic susceptibility to a number of occupational and environmental exposures including organochlorines, chlorinated solvents, chlordanes and benzene in the aetiology of NHL. The potential importance of these gene-environment interactions in NHL may help to explain the lack of definitive carcinogens identified to date for this malignancy. AREAS OF CONTROVERSY: Although a large number of genetic variants and gene-environment interactions have been explored for NHL, to date replication is lacking and therefore the findings remain to be validated. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: These findings highlight the need for novel standardized methodologies in the study of genetic susceptibility to chemical carcinogens. PMID- 25114270 TI - Police exposure to infectious agents: an audit of protective policies. AB - BACKGROUND: As first responders, police officers may be exposed to infectious agents such as hepatitis viruses and human immunodeficiency virus. Their risk of infection by these viruses can be reduced with training, monitoring and, with some viruses, vaccination. AIMS: To examine infection prevention policies and practices among police departments and determine provision of vaccination and infection prevention education programmes. METHODS: A questionnaire sent to all police departments in five counties of south-eastern Pennsylvania to capture information about department size, immunization policies and practices, record keeping, infection prevention education and monitoring of exposures. RESULTS: Ninety-six of 168 departments responded (57%). Among these, policies requiring pre-employment physical examinations were almost universal (95%). Vaccination policies were less common with <15% requiring and 50% recommending hepatitis, tetanus or influenza vaccination for officers. Few departments took action to provide (2%) or cover the cost (21%) of vaccination. Fewer than 12% maintained vaccination records. Education about the risk of infectious agents was offered by 60% of the responding departments, but often just once at the start of employment. Fewer than half of the departments had systems to collect exposure information. CONCLUSIONS: Police departments have opportunities to improve policies and practices for infection prevention and control. Accurate documentation of vaccination status is essential to ensure provision of appropriate post-exposure assessment and treatment. Better reporting of exposure will improve understanding of the infection transmission risk, enhancing the ability to offer targeted education and services to officers. PMID- 25114271 TI - Re: Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication. PMID- 25114272 TI - Response. PMID- 25114273 TI - Clinical genomics: when whole genome sequencing is like a whole-body CT scan. PMID- 25114274 TI - Improving the 510(k) FDA process for cardiac troponin assays: in search of common ground. PMID- 25114275 TI - EMA's proposal to vet drug research that uses its data is "outdated," say critics. PMID- 25114276 TI - Response. PMID- 25114277 TI - Commentary on the 2014 BP guidelines from the panel appointed to the Eighth Joint National Committee (JNC 8). AB - The recently published article "2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8)" (James et al., JAMA 311: 507-520, 2014) has generated considerable controversy. In this commentary, we evaluate the document and compare the recommendations contained within it with those of the JNC 7 and other national and international guidelines. The evidence quality rating approach followed by the article "2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee (JNC 8)" (James et al., JAMA 311: 507-520, 2014) disqualified nearly 98% of previous studies from review; as a result, some of the key recommendations were on the basis of expert opinion alone. We are especially concerned that the recommendation to raise the systolic/diastolic BP levels at which treatment is initiated to >=150/>=90 mmHg in adults>=60 years old may affect cardiovascular and renal health in these patients. Additionally, we recommend that hypertension guidelines should be updated every 3-4 years with a fresh approach to the definition of target BP levels, the use of modern technology in the diagnosis of hypertension, and the treatment of hypertension in special populations not addressed in earlier guidelines. PMID- 25114279 TI - Intrapleural lipoma mimicking a lung cancer. PMID- 25114280 TI - Bell's sign with lagophthalmos in leprosy. PMID- 25114281 TI - Periprocedural stroke presenting as isolated unilateral internuclear ophthalmoplegia. PMID- 25114278 TI - Genetic regulation of Zfp30, CXCL1, and neutrophilic inflammation in murine lung. AB - Allergic asthma is a complex disease characterized in part by granulocytic inflammation of the airways. In addition to eosinophils, neutrophils (PMN) are also present, particularly in cases of severe asthma. We sought to identify the genetic determinants of neutrophilic inflammation in a mouse model of house dust mite (HDM)-induced asthma. We applied an HDM model of allergic asthma to the eight founder strains of the Collaborative Cross (CC) and 151 incipient lines of the CC (preCC). Lung lavage fluid was analyzed for PMN count and the concentration of CXCL1, a hallmark PMN chemokine. PMN and CXCL1 were strongly correlated in preCC mice. We used quantitative trait locus (QTL) mapping to identify three variants affecting PMN, one of which colocalized with a QTL for CXCL1 on chromosome (Chr) 7. We used lung eQTL data to implicate a variant in the gene Zfp30 in the CXCL1/PMN response. This genetic variant regulates both CXCL1 and PMN by altering Zfp30 expression, and we model the relationships between the QTL and these three endophenotypes. We show that Zfp30 is expressed in airway epithelia in the normal mouse lung and that altering Zfp30 expression in vitro affects CXCL1 responses to an immune stimulus. Our results provide strong evidence that Zfp30 is a novel regulator of neutrophilic airway inflammation. PMID- 25114282 TI - Scleroderma and breast implants. PMID- 25114283 TI - Thromboembolic complications in the nephrotic syndrome. PMID- 25114284 TI - Seeking a better (residency) match. PMID- 25114285 TI - Metal water bottle causing tongue entrapment in a child. PMID- 25114286 TI - Health technology assessment: the journey continues. PMID- 25114288 TI - Inguinal hernia in a 55-year-old man. PMID- 25114289 TI - Exercise prescriptions endorsed. PMID- 25114290 TI - Medicare on trial. PMID- 25114293 TI - Triggering receptor expressed on myeloid cells 2 (TREM2) promotes adipogenesis and diet-induced obesity. AB - Triggering receptor expressed on myeloid cells 2 (TREM2) is known to be involved in the anti-inflammatory response and osteoclast development. However, the role of TREM2 in adipogenesis or obesity has not yet been defined. The effect of TREM2 on adipogenesis and obesity was investigated in TREM2 transgenic (TG) mice on a high-fat diet (HFD). To block TREM2 signaling, a neutralizing fusion protein specific for TREM2 (TREM2-Ig) was used. TG mice were much more obese than wild type mice after feeding with an HFD, independent of the quantity of food intake. These HFD-fed TG mice manifested adipocyte hypertrophy, glucose and insulin resistance, and hepatic steatosis. The expression of adipogenic regulator genes, such as peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding protein alpha, was markedly increased in HFD-fed TG mice. Additionally, HFD-fed TG mice exhibited decreased Wnt10b expression and increased GSK-3beta (glycogen synthase kinase-3beta)-mediated beta-catenin phosphorylation. In contrast, the blockade of TREM2 signaling using TREM2-Ig resulted in the inhibition of adipocyte differentiation in vitro and a reduction in body weight in vivo by downregulating the expression of adipogenic regulators. Our data demonstrate that TREM2 promotes adipogenesis and diet-induced obesity by upregulating adipogenic regulators in conjunction with inhibiting the Wnt10b/beta catenin signaling pathway. PMID- 25114291 TI - Generation of catalytic human Ago4 identifies structural elements important for RNA cleavage. AB - Argonaute proteins bind small RNAs and mediate cleavage of complementary target RNAs. The human Argonaute protein Ago4 is catalytically inactive, although it is highly similar to catalytic Ago2. Here, we have generated Ago2-Ago4 chimeras and analyzed their cleavage activity in vitro. We identify several specific features that inactivate Ago4: the catalytic center, short sequence elements in the N terminal domain, and an Ago4-specific insertion in the catalytic domain. In addition, we show that Ago2-mediated cleavage of the noncanonical miR-451 precursor can be carried out by any catalytic human Ago protein. Finally, phylogenetic analyses establish evolutionary distances between the Ago proteins. Interestingly, these distances do not fully correlate with the structural changes inactivating them, suggesting functional adaptations of individual human Ago proteins. PMID- 25114292 TI - Clinical and molecular characterization of a novel PLIN1 frameshift mutation identified in patients with familial partial lipodystrophy. AB - Perilipin 1 is a lipid droplet coat protein predominantly expressed in adipocytes, where it inhibits basal and facilitates stimulated lipolysis. Loss-of function mutations in the PLIN1 gene were recently reported in patients with a novel subtype of familial partial lipodystrophy, designated as FPLD4. We now report the identification and characterization of a novel heterozygous frameshift mutation affecting the carboxy-terminus (439fs) of perilipin 1 in two unrelated families. The mutation cosegregated with a similar phenotype including partial lipodystrophy, severe insulin resistance and type 2 diabetes, extreme hypertriglyceridemia, and nonalcoholic fatty liver disease in both families. Poor metabolic control despite maximal medical therapy prompted two patients to undergo bariatric surgery, with remarkably beneficial consequences. Functional studies indicated that expression levels of the mutant protein were lower than wild-type protein, and in stably transfected preadipocytes the mutant protein was associated with smaller lipid droplets. Interestingly, unlike the previously reported 398 and 404 frameshift mutants, this variant binds and stabilizes ABHD5 expression but still fails to inhibit basal lipolysis as effectively as wild-type perilipin 1. Collectively, these findings highlight the physiological need for exquisite regulation of neutral lipid storage within adipocyte lipid droplets, as well as the possible metabolic benefits of bariatric surgery in this serious disease. PMID- 25114295 TI - GLP-1 and exendin-4 transiently enhance GABAA receptor-mediated synaptic and tonic currents in rat hippocampal CA3 pyramidal neurons. AB - Glucagon-like peptide-1 (GLP-1) is a hormone that stimulates insulin secretion. Receptors for GLP-1 are also found in the brain, including the hippocampus, the center for memory and learning. Diabetes is a risk factor for decreased memory functions. We studied effects of GLP-1 and exendin-4, a GLP-1 receptor agonist, on gamma-aminobutyric acid (GABA) signaling in hippocampal CA3 pyramidal neurons. GABA is the main inhibitory neurotransmitter and decreases neuronal excitability. GLP-1 (0.01-1 nmol/L) transiently enhanced synaptic and tonic currents, and the effects were blocked by exendin (9-39). Ten pmol/L GLP-1 increased both the spontaneous inhibitory postsynaptic current (sIPSC) amplitudes and frequency by a factor of 1.8. In 0.1, 1 nmol/L GLP-1 or 10, 50, or 100 nmol/L exendin-4, only the sIPSC frequency increased. The tonic current was enhanced by 0.01-1 nmol/L GLP-1 and by 0.5-100 nmol/L exendin-4. When action potentials were inhibited by tetrodotoxin (TTX), inhibitory postsynaptic currents decreased and currents were no longer potentiated by GLP-1 or exendin-4. In contrast, although the tonic current decreased in TTX, it was still enhanced by GLP-1 or exendin-4. The results demonstrate GLP-1 receptor regulation of hippocampal function and are consistent with GLP-1 receptor agonists enhancing GABAA signaling by pre- and postsynaptic mechanisms. PMID- 25114294 TI - Perifornical hypothalamic orexin and serotonin modulate the counterregulatory response to hypoglycemic and glucoprivic stimuli. AB - Previous reports suggested an important role for serotonin (5-hydroxytryptamine [5-HT]) in enhancing the counterregulatory response (CRR) to hypoglycemia. To elucidate the sites of action mediating this effect, we initially found that insulin-induced hypoglycemia stimulates 5-HT release in widespread forebrain regions, including the perifornical hypothalamus (PFH; 30%), ventromedial hypothalamus (34%), paraventricular hypothalamus (34%), paraventricular thalamic nucleus (64%), and cerebral cortex (63%). Of these, we focused on the PFH because of its known modulation of diverse neurohumoral and behavioral responses. In awake, behaving rats, bilateral PFH glucoprivation with 5-thioglucose stimulated adrenal medullary epinephrine (Epi) release (3,153%) and feeding (400%), while clamping PFH glucose at postprandial brain levels blunted the Epi response to hypoglycemia by 30%. The PFH contained both glucose-excited (GE) and glucose inhibited (GI) neurons; GE neurons were primarily excited, while GI neurons were equally excited or inhibited by 5-HT at hypoglycemic glucose levels in vitro. Also, 5-HT stimulated lactate production by cultured hypothalamic astrocytes. Depleting PFH 5-HT blunted the Epi (but not feeding) response to focal PFH (69%) and systemic glucoprivation (39%), while increasing PFH 5-HT levels amplified the Epi response to hypoglycemia by 32%. Finally, the orexin 1 receptor antagonist SB334867A attenuated both the Epi (65%) and feeding (47%) responses to focal PFH glucoprivation. Thus we have identified the PFH as a glucoregulatory region where both 5-HT and orexin modulate the CRR and feeding responses to glucoprivation. PMID- 25114296 TI - Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). AB - OBJECTIVE: Insulin degludec/liraglutide (IDegLira) is a novel combination of insulin degludec (IDeg) and liraglutide. This trial investigated the contribution of the liraglutide component of IDegLira versus IDeg alone on efficacy and safety in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a 26-week, double-blind trial, patients with type 2 diabetes (A1C 7.5-10.0% [58-86 mmol/mol]) on basal insulin (20-40 units) and metformin with or without sulfonylurea/glinides were randomized (1:1) to once-daily IDegLira + metformin or IDeg + metformin with titration aiming for fasting plasma glucose between 4 and 5 mmol/L. Maximum allowed doses were 50 dose steps (equal to 50 units IDeg plus 1.8 mg liraglutide) and 50 units for IDeg. The primary end point was change in A1C from baseline. RESULTS: A total of 413 patients were randomized (mean A1C 8.8% [73 mmol/mol]; BMI 33.7 kg/m2). IDeg dose, alone or as part of IDegLira, was equivalent (45 units). A1C decreased by 1.9% (21 mmol/mol) with IDegLira and by 0.9% (10 mmol/mol) with IDeg (estimated treatment difference -1.1% [95% CI -1.3, 0.8], -12 mmol/mol [95% CI -14, -9; P < 0.0001). Mean weight reduction with IDegLira was 2.7 kg vs. no weight change with IDeg, P < 0.0001. Hypoglycemia incidence was comparable (24% for IDegLira vs. 25% for IDeg). Overall adverse events were similar, and incidence of nausea was low in both groups (IDegLira 6.5% vs. IDeg 3.5%). CONCLUSIONS: IDegLira achieved glycemic control superior to that of IDeg at equivalent insulin doses without higher risk of hypoglycemia and with the benefit of weight loss. These findings establish the efficacy and safety of IDegLira and the distinct contribution of the liraglutide component. PMID- 25114298 TI - At 15 years of follow-up, bariatric surgery, especially when performed within the first year, is associated with diabetes remission and reduced incidence of microvascular and macrovascular complications. PMID- 25114299 TI - Self-harm in young people. AB - Self-harm is a common problem among young people with many presenting to clinical services via general hospitals, but many more do not come to the attention of clinical services at all. Self-harm is strongly associated with completed suicide so it is extremely important that patients are assessed and treated for this problem effectively. Despite the scale of the problem in young people, there is a very limited evidence base on what interventions may help them to recover from self-harm. The evidence is discussed here and some recommendations are made about how to engage clinically with young people who self-harm from assessment to therapeutic intervention. PMID- 25114300 TI - Cumulative adversity in early childhood is associated with increased BMI and behavioural problems. AB - Implications for practice and research: Mental health problems and obesity are significant outcomes for children experiencing adversity in early life. Behavioural outcomes and body mass index (BMI) are more consistently reported for children experiencing adversity in early life compared with blood pressure (BP). Incomplete data due to drop out over time and a reliance on parental reporting are challenges for large longitudinal studies; future research directions include balancing and testing such investigations with smaller in-depth studies. PMID- 25114301 TI - New approaches to the Moon's isotopic crisis. AB - Recent comparisons of the isotopic compositions of the Earth and the Moon show that, unlike nearly every other body known in the Solar System, our satellite's isotopic ratios are nearly identical to the Earth's for nearly every isotopic system. The Moon's chemical make-up, however, differs from the Earth's in its low volatile content and perhaps in the elevated abundance of oxidized iron. This surprising situation is not readily explained by current impact models of the Moon's origin and offers a major clue to the Moon's formation, if we only could understand it properly. Current ideas to explain this similarity range from assuming an impactor with the same isotopic composition as the Earth to postulating a pure ice impactor that completely vaporized upon impact. Several recent proposals follow from the suggestion that the Earth-Moon system may have lost a great deal of angular momentum during early resonant interactions. The isotopic constraint may be the most stringent test yet for theories of the Moon's origin. PMID- 25114302 TI - Lunar-forming impacts: processes and alternatives. AB - The formation of a protolunar disc by a giant impact with the early Earth is discussed, focusing on two classes of impacts: (i) canonical impacts, in which a Mars-sized impactor produces a planet-disc system whose angular momentum is comparable to that in the current Earth and Moon, and (ii) high-angular-momentum impacts, which produce a system whose angular momentum is approximately a factor of 2 larger than that in the current Earth and Moon. In (i), the disc originates primarily from impactor-derived material and thus is expected to have an initial composition distinct from that of the Earth's mantle. In (ii), a hotter, more compact initial disc is produced with a silicate composition that can be nearly identical to that of the silicate Earth. Both scenarios require subsequent processes for consistency with the current Earth and Moon: disc-planet compositional equilibration in the case of (i), or large-scale angular momentum loss during capture of the newly formed Moon into the evection resonance with the Sun in the case of (ii). PMID- 25114303 TI - Terrestrial aftermath of the Moon-forming impact. AB - Much of the Earth's mantle was melted in the Moon-forming impact. Gases that were not partially soluble in the melt, such as water and CO2, formed a thick, deep atmosphere surrounding the post-impact Earth. This atmosphere was opaque to thermal radiation, allowing heat to escape to space only at the runaway greenhouse threshold of approximately 100 W m(-2). The duration of this runaway greenhouse stage was limited to approximately 10 Myr by the internal energy and tidal heating, ending with a partially crystalline uppermost mantle and a solid deep mantle. At this point, the crust was able to cool efficiently and solidified at the surface. After the condensation of the water ocean, approximately 100 bar of CO2 remained in the atmosphere, creating a solar-heated greenhouse, while the surface cooled to approximately 500 K. Almost all this CO2 had to be sequestered by subduction into the mantle by 3.8 Ga, when the geological record indicates the presence of life and hence a habitable environment. The deep CO2 sequestration into the mantle could be explained by a rapid subduction of the old oceanic crust, such that the top of the crust would remain cold and retain its CO2. Kinematically, these episodes would be required to have both fast subduction (and hence seafloor spreading) and old crust. Hadean oceanic crust that formed from hot mantle would have been thicker than modern crust, and therefore only old crust underlain by cool mantle lithosphere could subduct. Once subduction started, the basaltic crust would turn into dense eclogite, increasing the rate of subduction. The rapid subduction would stop when the young partially frozen crust from the rapidly spreading ridge entered the subduction zone. PMID- 25114304 TI - Lunar and terrestrial planet formation in the Grand Tack scenario. AB - We present conclusions from a large number of N-body simulations of the giant impact phase of terrestrial planet formation. We focus on new results obtained from the recently proposed Grand Tack model, which couples the gas-driven migration of giant planets to the accretion of the terrestrial planets. The giant impact phase follows the oligarchic growth phase, which builds a bi-modal mass distribution within the disc of embryos and planetesimals. By varying the ratio of the total mass in the embryo population to the total mass in the planetesimal population and the mass of the individual embryos, we explore how different disc conditions control the final planets. The total mass ratio of embryos to planetesimals controls the timing of the last giant (Moon-forming) impact and its violence. The initial embryo mass sets the size of the lunar impactor and the growth rate of Mars. After comparing our simulated outcomes with the actual orbits of the terrestrial planets (angular momentum deficit, mass concentration) and taking into account independent geochemical constraints on the mass accreted by the Earth after the Moon-forming event and on the time scale for the growth of Mars, we conclude that the protoplanetary disc at the beginning of the giant impact phase must have had most of its mass in Mars-sized embryos and only a small fraction of the total disc mass in the planetesimal population. From this, we infer that the Moon-forming event occurred between approximately 60 and approximately 130 Myr after the formation of the first solids and was caused most likely by an object with a mass similar to that of Mars. PMID- 25114305 TI - Rb-Sr, Sm-Nd and Lu-Hf isotope systematics of the lunar Mg-suite: the age of the lunar crust and its relation to the time of Moon formation. AB - New Rb-Sr, (146,147)Sm-(142,143)Nd and Lu-Hf isotopic analyses of Mg-suite lunar crustal rocks 67667, 76335, 77215 and 78238, including an internal isochron for norite 77215, were undertaken to better define the time and duration of lunar crust formation and the history of the source materials of the Mg-suite. Isochron ages determined in this study for 77215 are: Rb-Sr=4450+/-270 Ma, (147)Sm (143)Nd=4283+/-23 Ma and Lu-Hf=4421+/-68 Ma. The data define an initial (146)Sm/(144)Sm ratio of 0.00193+/-0.00092 corresponding to ages between 4348 and 4413 Ma depending on the half-life and initial abundance used for (146)Sm. The initial Nd and Hf isotopic compositions of all samples indicate a source region with slight enrichment in the incompatible elements in accord with previous suggestions that the Mg-suite crustal rocks contain a component of KREEP. The Sm/Nd-(142)Nd/(144)Nd correlation shown by both ferroan anorthosite and Mg-suite rocks is coincident with the trend defined by mare and KREEP basalts, the slope of which corresponds to ages between 4.35 and 4.45 Ga. These data, along with similar ages for various early Earth differentiation events, are in accord with the model of lunar formation via giant impact into Earth at ca 4.4 Ga. PMID- 25114306 TI - Isotopes as tracers of the sources of the lunar material and processes of lunar origin. AB - Ever since the Apollo programme, isotopic abundances have been used as tracers to study lunar formation, in particular to study the sources of the lunar material. In the past decade, increasingly precise isotopic data have been reported that give strong indications that the Moon and the Earth's mantle have a common heritage. To reconcile these observations with the origin of the Moon via the collision of two distinct planetary bodies, it has been proposed (i) that the Earth-Moon system underwent convective mixing into a single isotopic reservoir during the approximately 10(3) year molten disc epoch after the giant impact but before lunar accretion, or (ii) that a high angular momentum impact injected a silicate disc into orbit sourced directly from the mantle of the proto-Earth and the impacting planet in the right proportions to match the isotopic observations. Recently, it has also become recognized that liquid-vapour fractionation in the energetic aftermath of the giant impact is capable of generating measurable mass dependent isotopic offsets between the silicate Earth and Moon, rendering isotopic measurements sensitive not only to the sources of the lunar material, but also to the processes accompanying lunar origin. Here, we review the isotopic evidence that the silicate-Earth-Moon system represents a single planetary reservoir. We then discuss the development of new isotopic tracers sensitive to processes in the melt-vapour lunar disc and how theoretical calculations of their behaviour and sample observations can constrain scenarios of post-impact evolution in the earliest history of the Earth-Moon system. PMID- 25114307 TI - Accretion of the Moon from non-canonical discs. AB - Impacts that leave the Earth-Moon system with a large excess in angular momentum have recently been advocated as a means of generating a protolunar disc with a composition that is nearly identical to that of the Earth's mantle. We here investigate the accretion of the Moon from discs generated by such 'non canonical' impacts, which are typically more compact than discs produced by canonical impacts and have a higher fraction of their mass initially located inside the Roche limit. Our model predicts a similar overall accretional history for both canonical and non-canonical discs, with the Moon forming in three consecutive steps over hundreds of years. However, we find that, to yield a lunar mass Moon, the more compact non-canonical discs must initially be more massive than implied by prior estimates, and only a few of the discs produced by impact simulations to date appear to meet this condition. Non-canonical impacts require that capture of the Moon into the evection resonance with the Sun reduced the Earth-Moon angular momentum by a factor of 2 or more. We find that the Moon's semi-major axis at the end of its accretion is approximately 7R?, which is comparable to the location of the evection resonance for a post-impact Earth with a 2.5 h rotation period in the absence of a disc. Thus, the dynamics of the Moon's assembly may directly affect its ability to be captured into the resonance. PMID- 25114297 TI - Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. PMID- 25114309 TI - Lunar bulk chemical composition: a post-Gravity Recovery and Interior Laboratory reassessment. AB - New estimates of the thickness of the lunar highlands crust based on data from the Gravity Recovery and Interior Laboratory mission, allow us to reassess the abundances of refractory elements in the Moon. Previous estimates of the Moon fall into two distinct groups: earthlike and a 50% enrichment in the Moon compared with the Earth. Revised crustal thicknesses and compositional information from remote sensing and lunar samples indicate that the crust contributes 1.13-1.85 wt% Al2O3 to the bulk Moon abundance. Mare basalt Al2O3 concentrations (8-10 wt%) and Al2O3 partitioning behaviour between melt and pyroxene during partial melting indicate mantle Al2O3 concentration in the range 1.3-3.1 wt%, depending on the relative amounts of pyroxene and olivine. Using crustal and mantle mass fractions, we show that that the Moon and the Earth most likely have the same (within 20%) concentrations of refractory elements. This allows us to use correlations between pairs of refractory and volatile elements to confirm that lunar abundances of moderately volatile elements such as K, Rb and Cs are depleted by 75% in the Moon compared with the Earth and that highly volatile elements, such as Tl and Cd, are depleted by 99%. The earthlike refractory abundances and depleted volatile abundances are strong constraints on lunar formation processes. PMID- 25114308 TI - Understanding the origin and evolution of water in the Moon through lunar sample studies. AB - A paradigm shift has recently occurred in our knowledge and understanding of water in the lunar interior. This has transpired principally through continued analysis of returned lunar samples using modern analytical instrumentation. While these recent studies have undoubtedly measured indigenous water in lunar samples they have also highlighted our current limitations and some future challenges that need to be overcome in order to fully understand the origin, distribution and evolution of water in the lunar interior. Another exciting recent development in the field of lunar science has been the unambiguous detection of water or water ice on the surface of the Moon through instruments flown on a number of orbiting spacecraft missions. Considered together, sample-based studies and those from orbit strongly suggest that the Moon is not an anhydrous planetary body, as previously believed. New observations and measurements support the possibility of a wet lunar interior and the presence of distinct reservoirs of water on the lunar surface. Furthermore, an approach combining measurements of water abundance in lunar samples and its hydrogen isotopic composition has proved to be of vital importance to fingerprint and elucidate processes and source(s) involved in giving rise to the lunar water inventory. A number of sources are likely to have contributed to the water inventory of the Moon ranging from primordial water to meteorite-derived water ice through to the water formed during the reaction of solar wind hydrogen with the lunar soil. Perhaps two of the most striking findings from these recent studies are the revelation that at least some portions of the lunar interior are as water-rich as some Mid-Ocean Ridge Basalt source regions on Earth and that the water in the Earth and the Moon probably share a common origin. PMID- 25114310 TI - Contraction or expansion of the Moon's crust during magma ocean freezing? AB - The lack of contraction features on the Moon has been used to argue that the Moon underwent limited secular cooling, and thus had a relatively cool initial state. A cool early state in turn limits the depth of the lunar magma ocean. Recent GRAIL gravity measurements, however, suggest that dikes were emplaced in the lower crust, requiring global lunar expansion. Starting from the magma ocean state, we show that solidification of the lunar magma ocean would most likely result in expansion of the young lunar crust, and that viscous relaxation of the crust would prevent early tectonic features of contraction or expansion from being recorded permanently. The most likely process for creating the expansion recorded by the dikes is melting during cumulate overturn of the newly solidified lunar mantle. PMID- 25114311 TI - Evaporative fractionation of volatile stable isotopes and their bearing on the origin of the Moon. AB - The Moon is depleted in volatile elements relative to the Earth and Mars. Low abundances of volatile elements, fractionated stable isotope ratios of S, Cl, K and Zn, high MU ((238)U/(204)Pb) and long-term Rb/Sr depletion are distinguishing features of the Moon, relative to the Earth. These geochemical characteristics indicate both inheritance of volatile-depleted materials that formed the Moon and planets and subsequent evaporative loss of volatile elements that occurred during lunar formation and differentiation. Models of volatile loss through localized eruptive degassing are not consistent with the available S, Cl, Zn and K isotopes and abundance data for the Moon. The most probable cause of volatile depletion is global-scale evaporation resulting from a giant impact or a magma ocean phase where inefficient volatile loss during magmatic convection led to the present distribution of volatile elements within mantle and crustal reservoirs. Problems exist for models of planetary volatile depletion following giant impact. Most critically, in this model, the volatile loss requires preferential delivery and retention of late-accreted volatiles to the Earth compared with the Moon. Different proportions of late-accreted mass are computed to explain present-day distributions of volatile and moderately volatile elements (e.g. Pb, Zn; 5 to >10%) relative to highly siderophile elements (approx. 0.5%) for the Earth. Models of early magma ocean phases may be more effective in explaining the volatile loss. Basaltic materials (e.g. eucrites and angrites) from highly differentiated airless asteroids are volatile-depleted, like the Moon, whereas the Earth and Mars have proportionally greater volatile contents. Parent-body size and the existence of early atmospheres are therefore likely to represent fundamental controls on planetary volatile retention or loss. PMID- 25114312 TI - Heterogeneity in lunar anorthosite meteorites: implications for the lunar magma ocean model. AB - The lunar magma ocean model is a well-established theory of the early evolution of the Moon. By this model, the Moon was initially largely molten and the anorthositic crust that now covers much of the lunar surface directly crystallized from this enormous magma source. We are undertaking a study of the geochemical characteristics of anorthosites from lunar meteorites to test this model. Rare earth and other element abundances have been measured in situ in relict anorthosite clasts from two feldspathic lunar meteorites: Dhofar 908 and Dhofar 081. The rare earth elements were present in abundances of approximately 0.1 to approximately 10* chondritic (CI) abundance. Every plagioclase exhibited a positive Eu-anomaly, with Eu abundances of up to approximately 20*CI. Calculations of the melt in equilibrium with anorthite show that it apparently crystallized from a magma that was unfractionated with respect to rare earth elements and ranged in abundance from 8 to 80*CI. Comparisons of our data with other lunar meteorites and Apollo samples suggest that there is notable heterogeneity in the trace element abundances of lunar anorthosites, suggesting these samples did not all crystallize from a common magma source. Compositional and isotopic data from other authors also suggest that lunar anorthosites are chemically heterogeneous and have a wide range of ages. These observations may support other models of crust formation on the Moon or suggest that there are complexities in the lunar magma ocean scenario to allow for multiple generations of anorthosite formation. PMID- 25114313 TI - Siderophile element constraints on the origin of the Moon. AB - Discovery of small enrichments in (182)W/(184)W in some Archaean rocks, relative to modern mantle, suggests both exogeneous and endogenous modifications to highly siderophile element (HSE) and moderately siderophile element abundances in the terrestrial mantle. Collectively, these isotopic enrichments suggest the formation of chemically fractionated reservoirs in the terrestrial mantle that survived the putative Moon-forming giant impact, and also provide support for the late accretion hypothesis. The lunar mantle sources of volcanic glasses and basalts were depleted in HSEs relative to the terrestrial mantle by at least a factor of 20. The most likely explanations for the disparity between the Earth and Moon are either that the Moon received a disproportionately lower share of late accreted materials than the Earth, such as may have resulted from stochastic late accretion, or the major phase of late accretion occurred prior to the Moon forming event, and the putative giant impact led to little drawdown of HSEs to the Earth's core. High precision determination of the (182)W isotopic composition of the Moon can help to resolve this issue. PMID- 25114314 TI - On the evolution of the protolunar disc. AB - The structure and viscous evolution of a post-impact, protolunar disc is examined. The equations for a silicate disc in two-phase (vapour-liquid) equilibrium are employed to derive an analytical solution to vertical structure. Both a vertically mixed phase disc and a stratified disc, where a magma layer exists in the mid-plane surrounded by a vapour reservoir, are considered. The former largely reproduces the low gas mass fraction, x?1, profiles of the disc described in earlier literature that proposed that the disc would hover on the brink of gravitational instability. In the latter, the vapour layer has x~1 and is generally gravitationally stable, while the magma layer is vigorously unstable. The viscous evolution of the stratified model is then explored. Initially, the disc quickly settles to a quasi-steady state with a vapour reservoir containing the majority of the disc mass. The magma layer viscously spreads on a time scale of approximately 3-4 years, during which vapour continuously condenses into droplets that settle to the mid-plane, maintaining the magma surface density in spite of disc spreading. Material flowing inwards is accreted by the Earth; material flowing outwards past the Roche boundary can become incorporated into accreting moonlets. This evolution persists until the vapour reservoir is depleted in approximately 50-100 years, depending on its initial mass. PMID- 25114315 TI - The giant impact hypothesis: past, present (and future?). AB - At the request of editors, this paper offers a historical review of early work on the giant impact hypothesis, as well as comments on new data. The author hereby claims (whether believable or not) that his interest is to move towards a correct model of lunar origin, not to defend a possibly incorrect idea, just because of being a co-author of a relevant early paper. Nonetheless, the 1974 giant impact hypothesis appears still to be viable. PMID- 25114317 TI - The iodine-plutonium-xenon age of the Moon-Earth system revisited. AB - Iodine-plutonium-xenon isotope systematics have been used to re-evaluate time constraints on the early evolution of the Earth-atmosphere system and, by inference, on the Moon-forming event. Two extinct radionuclides ((129)I, T1/2=15.6 Ma and (244)Pu, T1/2=80 Ma) have produced radiogenic (129)Xe and fissiogenic (131-136)Xe, respectively, within the Earth, the related isotope fingerprints of which are seen in the compositions of mantle and atmospheric Xe. Recent studies of Archaean rocks suggest that xenon atoms have been lost from the Earth's atmosphere and isotopically fractionated during long periods of geological time, until at least the end of the Archaean eon. Here, we build a model that takes into account these results. Correction for Xe loss permits the computation of new closure ages for the Earth's atmosphere that are in agreement with those computed for mantle Xe. The corrected Xe formation interval for the Earth-atmosphere system is [Formula: see text] Ma after the beginning of Solar System formation. This time interval may represent a lower limit for the age of the Moon-forming impact. PMID- 25114316 TI - Geochemical arguments for an Earth-like Moon-forming impactor. AB - Geochemical evidence suggests that the material accreted by the Earth did not change in nature during Earth's accretion, presumably because the inner protoplanetary disc had uniform isotopic composition similar to enstatite chondrites, aubrites and ungrouped achondrite NWA 5363/5400. Enstatite meteorites and the Earth were derived from the same nebular reservoir but diverged in their chemical evolutions, so no chondrite sample in meteorite collections is representative of the Earth's building blocks. The similarity in isotopic composition (Delta(17)O, epsilon(50)Ti and epsilon(54)Cr) between lunar and terrestrial rocks is explained by the fact that the Moon-forming impactor came from the same region of the disc as other Earth-forming embryos, and therefore was similar in isotopic composition to the Earth. The heavy delta(30)Si values of the silicate Earth and the Moon relative to known chondrites may be due to fractionation in the solar nebula/protoplanetary disc rather than partitioning of silicon in Earth's core. An inversion method is presented to calculate the Hf/W ratios and epsilon(182)W values of the proto-Earth and impactor mantles for a given Moon-forming impact scenario. The similarity in tungsten isotopic composition between lunar and terrestrial rocks is a coincidence that can be explained in a canonical giant impact scenario if an early formed embryo (two stage model age of 10-20 Myr) collided with the proto-Earth formed over a more protracted accretion history (two-stage model age of 30-40 Myr). PMID- 25114319 TI - The origin of the Moon. Preface. PMID- 25114318 TI - Lunar exploration: opening a window into the history and evolution of the inner Solar System. AB - The lunar geological record contains a rich archive of the history of the inner Solar System, including information relevant to understanding the origin and evolution of the Earth-Moon system, the geological evolution of rocky planets, and our local cosmic environment. This paper provides a brief review of lunar exploration to-date and describes how future exploration initiatives will further advance our understanding of the origin and evolution of the Moon, the Earth-Moon system and of the Solar System more generally. It is concluded that further advances will require the placing of new scientific instruments on, and the return of additional samples from, the lunar surface. Some of these scientific objectives can be achieved robotically, for example by in situ geochemical and geophysical measurements and through carefully targeted sample return missions. However, in the longer term, we argue that lunar science would greatly benefit from renewed human operations on the surface of the Moon, such as would be facilitated by implementing the recently proposed Global Exploration Roadmap. PMID- 25114320 TI - Shortening the culture time in cytogenetic dosimetry using PCC-R assay. AB - The fast assessment of the dose received by exposed persons is crucial in radiological accidents, so the 48 h of cell culture in conventional cytogenetic dosimetry in addition to some limitations after high doses becomes a disadvantage. The premature chromosome condensation (PCC) assay permits to analyse enough cells after high radiation exposure, and the score of PCC-R may reduce the culture time up to 40-42 h. Peripheral whole-blood samples were exposed to 1-10 Gy of gamma radiation and cultured during 40 and 42 h. No statistical difference between frequencies was obtained between 40, 42 and 48 h of culture time, and PCC index decreased with the increase of the dose and increased with the culture time. The protocol proposed allows reduce the culture time down to 40 or 42 h when using the PCC-R assay with adequate precision in dose estimation. PMID- 25114322 TI - Verified clinical failure with cefotaxime 1g for treatment of gonorrhoea in the Netherlands: a case report. AB - We describe the first case of treatment failure of gonorrhoea with a third generation cephalosporin, cefotaxime 1g intramuscularly, in the Netherlands. The case was from a high-frequency transmitting population (men having sex with men) and was caused by the internationally spreading multidrug-resistant gonococcal NG MAST ST1407 clone. The patient was clinically cured after treatment with ceftriaxone 500 mg intramuscularly and this is the only third generation cephalosporin that should be used for first-line empiric treatment of gonorrhoea. Increased awareness of failures with third generation cephalosporins, enhanced monitoring and appropriate verification of treatment failures including more frequent test-of-cures, and strict adherence to regularly updated treatment guidelines are essential globally. PMID- 25114321 TI - Conformance of mean glandular dose from phantom and patient data in mammography. AB - In mammography dosimetry, phantoms are often used to represent breast tissue. The conformance of phantom- and patient-based mean glandular dose (MGD) estimates was evaluated mainly from the aspect of diagnostic reference levels. Patient and phantom exposure data were collected for eight diagnostic and three screening mammography devices. More extensive assessments were performed for two devices. The average breast thickness was close to the nationally used reference of 50 mm in diagnostic (50 mm, SD = 13 mm, n = 5342) and screening (47 mm, SD = 13 mm, n = 395) examinations. The average MGD for all breasts differed by 2% from the MGD determined for breasts in the limited compressed thickness range of 40-60 mm. The difference between phantom- and patient-based MGD estimations was up to 30%. Therefore, phantom measurements cannot replace patient dose data in MGD determination. PMID- 25114323 TI - Embolized ductus device extraction and associated iliofemoral artery repair. AB - Less-invasive methods for nonsurgical closure of a patent ductus arteriosus have gained popularity as first-line therapy. An 11-year-old girl underwent percutaneous patent ductus arteriosus closure with a device. The device embolized into the descending aorta. An attempt at catheter retrieval was complicated by iliofemoral arterial injury. Subsequent device extraction was performed with repair of the arterial injury using a tube graft. PMID- 25114324 TI - Is serotonin a valuable parameter in peripheral arterial disease? AB - OBJECTIVE: In this study, we aimed to evaluate the relationship of serum serotonin levels, which are supposed to affect vascular function, to peripheral arterial disease. METHODS: This prospective study was performed in 70 patients (57 males, 13 females; mean age 67 +/- 13 years) with peripheral arterial disease scheduled for surgery and 70 controls (52 males, 18 females; mean age 58 +/- 12 years). RESULTS: The rates of diabetes mellitus and hypertension and the fasting glucose levels were significantly higher in the peripheral arterial disease group (p = 0.001). Total, low-density, and high-density cholesterol, triglycerides, urea, and creatinine levels, and the smoking rate were similar in both groups (p > 0.05). The serotonin levels were significantly higher in patients with peripheral vascular disease scheduled for surgery compared to the control group (p = 0.024). CONCLUSION: The plasma serotonin level is an important parameter in peripheral arterial disease. PMID- 25114325 TI - Omento-myoplasty for postpneumonectomy empyema. PMID- 25114326 TI - Posterior leaflet segment 2 plication in ischemic mitral regurgitation repair. AB - AIM: To evaluate the medium-term results of plication of posterior leaflet segment 2 in addition to ring annuloplasty in patients with functional ischemic mitral regurgitation. METHODS: The study included 136 patients who underwent mitral valve repair with plication of posterior leaflet segment 2 for ischemic mitral regurgitation between 2004 and 2012. The direction and correlation of left ventricle sphericity and tethering area were established by Pearson correlation analysis in patients with or without recurrent mitral regurgitation in the medium term. RESULTS: Medium-term survival was 91.9% and freedom from moderate or severe mitral regurgitation was 89.6%. In medium-term follow-up, transthoracic echocardiography found a significant decrease in tethering area, coaptation height, and distance between the commissures compared to the pre-surgery values (p = 0.0001 in all). The distance between the papillary muscles was reduced compared to the pre-surgery period but it was not significant (p = 0.204). Pearson correlation analysis found no significant correlation between the tethering area and left ventricle sphericity in patients without recurrent mitral regurgitation (r = 0.15, p = 0.36), a highly positive correlation (r = 0.44, p < 0.001) in patients with mild recurrent mitral regurgitation, and a moderately positive correlation (r = 0.71, p < 0.01) in patients with moderate or severe recurrent mitral regurgitation. CONCLUSIONS: The tethering area, coaptation height, and distance between the commissures decreased significantly, thus posterior leaflet segment 2 plication in addition to ring annuloplasty may be the optional procedure to ensure freedom from moderate or severe mitral regurgitation. PMID- 25114327 TI - Serial hemodynamic measurements in post-cardiac arrest cardiogenic shock treated with therapeutic hypothermia. AB - AIMS: Mortality from cardiogenic shock complicating acute myocardial infarction (MI) remains high despite contemporary treatment. Therapeutic Hypothermia (TH) offers cardiovascular and systemic effects that may prove beneficial in this population, however, current data are limited. This study sought to evaluate the effect of therapeutic hypothermia on serial hemodynamics obtained in subjects with post-cardiac arrest cardiogenic shock. METHODS: We analyzed serial hemodynamics of 14 consecutive patients with cardiogenic shock after cardiac arrest treated with TH. Study inclusion required baseline hemodynamics obtained prior to initiation of TH confirming cardiogenic shock defined as cardiac index <=2.2 L/min/m(2) with a systolic blood pressure of <=90 mmHg, a vasopressor requirement, or need for mechanical circulatory support. RESULTS: In our 14 patients, the mean age was 58 +/- 13.1 years, mean ejection fraction was 21 +/- 8%, six had an acute MI, 12 required vasopressors, and 10 required mechanical support prior to initiation of TH. When compared to baseline, patients had significant improvements in Fick cardiac index, mixed venous O2 saturations, and serum lactate concentrations while heart rate was reduced following initiation of TH. There was no significant change in mean arterial pressure, however vasopressor requirement was reduced. CONCLUSIONS: In patients with cardiogenic shock following cardiac arrest, initiation of TH was associated with favorable changes in invasive hemodynamics suggesting safety in this population. Given potential for favorable hemodynamic and systemic effects of TH in cardiogenic shock, further prospective study of TH as a potentially novel adjunctive therapy to early reperfusion in post-MI cardiogenic shock should be considered. PMID- 25114328 TI - Impact of out-of-hospital cardiac arrest due to ventricular fibrillation in patients with ST-elevation myocardial infarction admitted for primary percutaneous coronary intervention: Impact of ventricular fibrillation in STEMI patients. AB - OBJECTIVE: Pre-hospital life-threatening ventricular tachycardia/fibrillation (VT/VF) is relatively common in the acute phase of ST-elevation myocardial infarction (STEMI). We evaluated the prognostic impact of out-of-hospital cardiac arrest (OHCA) due to VT/VF in non-selected patients with STEMI admitted for primary percutaneous coronary intervention (PCI). METHODS: Prospective hospital registry was used to collect data of consecutive STEMI patients admitted to our hospital between 2005 and 2010. Patients with OHCA were identified from this registry, and their medical records were reviewed. RESULTS: During the study period, 4653 patients were admitted with STEMI. Data regarding OHCA due to VT/VF was available in 4643 patients (99.8%). A total of 326 patients (7.0%) had OHCA due to VT/VF. Patients with OHCA were younger (60.3 +/- 11.8 vs. 64.1 +/- 12.9 year, p<0.001), less often had diabetes (5.2% vs. 12.4%, p<0.001) but more often presented with signs of heart failure (Killip class >1:17.5% vs. 7.7%, p<0.001) and cardiogenic shock (29.6% vs. 2.5%, p<0.001). Coronary angiography was performed in 97.5% of the patients. Coronary angiography and primary PCI were performed equally in both groups. In patients with OHCA, the left main artery (2.3% vs. 1.0%, p=0.04) and LAD (49.2% vs. 41.2%, p=0.01) were more often the culprit artery. In-hospital mortality was significantly higher among patients with OHCA (13.80% vs. 3.4%, p<0.001). However, in patients who were discharged alive from the hospital, the one-year mortality and the combined incidence of death and appropriate ICD therapy were similar in patients with and without OHCA. CONCLUSION: In a large non-selected STEMI patient population admitted for primary PCI, OHCA due to VT/VF was associated with higher in-hospital mortality but did not affect the long-term prognosis. PMID- 25114329 TI - Excellence in acute cardiac care: an overview of the seminar proceedings. PMID- 25114330 TI - Non-contact multi-particle annular patterning and manipulation with ultrasound microbeam. AB - Multiparticle-trapping offers diverse opportunities and applications in biotechnology. It can be applied to creating various functional materials or organizing reactive particles. In this paper, we demonstrate that it is possible to trap and manipulate multi-particles in an annular pattern with a 24 MHz focused ring-type single element ultrasound transducer. Acoustic ring trap can be useful in undertaking biotropism studies due to an equal-distance condition from the center. Also, this ring trap could serve as a force shield to protect analysis area from other cells. The experimental results showed the capability of the proposed method as a multi-cell manipulator in formatting specific patterns of small cells like sperms. PMID- 25114331 TI - Determination of full set material constants of [011]c poled 0.72Pb(Mg1/3Nb2/3)O3 0.28PbTiO3 single crystal from one sample. AB - 0.72Pb(Mg1/3Nb2/3)O3-0.28PbTiO3 single crystals poled along [011]c have macroscopic orthorhombic mm2 symmetry. There are total 17 independent material coefficients for this symmetry so that the determination of self-consistent full matrix data is extremely difficult because many samples are needed and there is a large property variation from sample to sample. To overcome this self-consistency difficulty, we have developed a combined ultrasonic pulse-echo and impedance spectroscopy method, which can extract all coefficients from only one small sample. This method is especially useful for piezoelectric materials whose properties are strongly dependent on geometry and for crystals with only limited size available. PMID- 25114332 TI - Synthesis of mono-dispersed nanofluids using solution plasma. AB - Small-sized and well-dispersed gold nanoparticles (NPs) for nanofluidics have been synthesized by electrical discharge in liquid environment using termed solution plasma processing (SPP). Electrons and the hydrogen radicals are reducing the gold ions to the neutral form in plasma gas phase and liquid phase, respectively. The gold NPs have the smallest diameter of 4.9 nm when the solution temperature was kept at 20 degrees C. Nucleation and growth theory describe the evolution of the NP diameter right after the reduction reaction in function of the system temperature, NP surface energy, dispersion energy barrier, and nucleation rate. Negative charges on the NPs surface during and after SPP generate repulsive forces among the NPs avoiding their agglomeration in solution. Increasing the average energy in the SPP determines a decrease of the zeta potential and an increase of the NPs diameter. An important enhancement of the thermal conductivity of 9.4% was measured for the synthesized nanofluids containing NPs with the smallest size. PMID- 25114333 TI - Significance of coarse cereals in health and nutrition: a review. AB - This review assesses the nutritional attributes of coarse cereals and also their utilization as food and as formulated foods. These cereals are laden with phytochemicals including phenolic acids, tannins, anthocyanins, phytosterols, avenenathramides and policosanols. They possess high antioxidant properties in vitro than staple cereals and fruits by different purported pathways. There are also some anti-nutritional factors that may be reduced by certain processing treatments. Several epidemiological studies show that these cereals are helpful in reducing several kinds of chronic diseases like cancers, cardiovascular diseases, type II diabetes and various gastrointestinal disorders. Being coarse in nature, they cannot replace our staple cereals, but can be used in different proportions with rice and wheat to formulate various nutritional products. They can be used to make porridges, biscuits, cakes, cookies, tortillas, bread, probiotic drinks, ladoo, ghatta, flakes and several fermented foods. The coarse cereals also have good potential in manufacturing bioethanol, paper, oil and biofilms. PMID- 25114334 TI - Nutritional quality of fresh and heated Aleppo pine (Pinus halepensis Mill.) seed oil: trans-fatty acid isomers profiles and antioxidant properties. AB - Numerous studies have focused on trans fatty acids (TFA) technologically produced by partial hydrogenation of oils. However, TFA can also be present in fresh oils. For this reason, cis fatty acid (CFA), TFA and conjugated linoleic acid (CLA) of fresh and heated Aleppo pine seed oil (APSO) at frying temperature (180 degrees C) were evaluated and correlated with the antioxidant characteristics. Results showed that fresh APSO had a low oleic/linoleic ratio O/L (0.4). Total TFA in fresh APSO reached 1%. The predominant TFA was 18:2 n-6 (t9, t12) in both fresh and heated APSO. Individual TFA increased with significant differences (p < 0.05) with heating time. CLA occurred after 4 h and significantly increased (p < 0.05) accounting 10% of total TFA after 10 h. Total TFA are negatively correlated with alpha-tocopherol, gamma-tocopherol (p < 0.05) and carotenoids (p < 0.01) and positively correlated with remaining DPPH. Oil stability index (OSI) showed significant negative correlation with TFA (r = -0.925; p = 0.008). A principal component analysis (PCA) showed a clear discrimination between fresh and heated oils. Temperature, heating time, unsaturation degree and antioxidants are combined factors which significantly affect the isomerization rate and nutritional quality of APSO. PMID- 25114335 TI - Characterization and storage stability of the extract of Thai mango (Mangifera indica Linn. Cultivar Chok-Anan) seed kernels. AB - Qualitative analysis of hydrolysable extract from mango (Mangifera indica Linn. cultivar Chok-Anan) seed kernel was performed by means of reversed phase high performance liquid chromatography coupled to diode array detection and electrospray ionization mass spectrometry (RPHPLC-DAD-ESI-MS). The main phenolic compound was identified as methyl gallate by comparing their retention time, UV vis absorption spectra and mass spectra with a reference standard. Quantification of phenolic compounds was performed by HPLC-DAD, which revealed that the extract contained total phenolics at a concentration of 194.1 mg GAE/g dry weight of mango seed kernel (MSK), of which 85.7% was identified as methyl gallate. In addition, the antioxidant activities of the extract and the main compound were assessed by the 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3 ethylbenzothiazoline-6-sulfonic acid) assays, by the ferric thiocyanate method and by an assay of metal chelating activity. Tyrosinase inhibition was also investigated. Furthermore, the antioxidant capacity and the total phenolic content of MSK extract stored in a plastic (polyethylene) PE bag decreased during storage at freezing (-20 degrees C), refrigerated (7 degrees C) and room (28-32 degrees C) temperature for 182 days. The loss of antioxidant capacity and total phenolic content increased at higher storage temperatures for more than 182 days. PMID- 25114336 TI - Modification of wheat starch with succinic acid/acetanhydride and azelaic acid/acetanhydride mixtures. II. Chemical and physical properties. AB - The aim of this research was to investigate the influence of modification with succinic acid/acetanhydride and azelaic acid/acetanhydride mixtures on chemical and physical properties of wheat starch. Starch was isolated from two wheat varieties and modified with mixtures of succinic acid and acetanhydride and azelaic acid and acetanhydride in 4, 6 and 8% (w/w). Total starch content, resistant starch content, degree of modification, changes in FT-IR spectra, colour, gel texture and freeze-thaw stability were determined. Results showed that resistant starch content increased by both investigated modifications, and degree of modification increased proportionally to amount of reagents used. FT-IR analysis of modified starches showed peak around 1,740 cm(-1), characteristic for carbonyl group of ester. Total colour difference caused by modifications was detectable by trained people. Adhesiveness significantly increased, while freeze thaw stability decreased by both investigated modifications. PMID- 25114337 TI - Chemical composition, molecular weight distribution, secondary structure and effect of NaCl on functional properties of walnut (Juglans regia L) protein isolates and concentrates. AB - Chemical composition, molecular weight distribution, secondary structure and effect of sodium chloride concentration on functional properties of walnut protein isolates, concentrates and defatted walnut flour were study. Compared with walnut protein concentrates (75.6%) and defatted walnut flour (52.5%), walnut protein isolates contain a relatively high amount of protein (90.5%). The yield of walnut protein isolates and concentrates was 43.2% and 76.6%, respectively. In molecular weight distribution study, Walnut protein isolates showed one peak with molecular weight of 106.33 KDa (100%) and walnut protein concentrates showed four peaks with molecular weight of 16,725 KDa (0.8%),104.943 KDa(63.9%), 7.3 KDa (11.4%), 2.6 KDa (23.9%). The secondary structure of walnut protein isolates was similar to that of walnut protein concentrates, but was differ from that of defatted walnut flour. The addition of sodium chloride (0 ~ 1 M) could improve the functionality of walnut protein concentrates, isolates and defatted walnut flour. The maximum solubility, water absorption capacity, emulsifying properties and foaming properties of walnut protein isolates, concentrates and defatted walnut flour were at sodium chloride solutions of 1.0 M, 0.6 M, 0.4 M, 0.6 M, respectively. The solubility of walnut protein concentrates (32.5%) in distilled water with 0 M sodium chloride was lower than that of walnut protein isolates (35.2%). The maximum solubility of walnut protein isolates, concentrates and defatted walnut flour in solution were 36.8%, 33.7% and 9.6% at 1.0 M sodium chloride solutions, respectively. As compared with other vegetable proteins, walnut protein isolates and concentrates exhibited better emulsifying properties and foam stability. PMID- 25114338 TI - Important nutritional constituents, flavour components, antioxidant and antibacterial properties of Pleurotus sajor-caju. AB - Oyster mushroom (Pleurotus sajor-caju) cultivated in the laboratory was studied for nutritional constituents, flavor components, antioxidant and antibacterial properties. Nutritional constituents estimated per 100 g dry weight (d.w.) include protein (29.3 g), carbohydrate (62.97 g), crude fat (0.91 g), ash (6.82 g) and crude fiber (12.3 g). Energy value of this mushroom was about 297.5 kcal/100 g d.w. Major mineral components estimated include Ca, Fe, and Mg with highest level of 505.0, 109.5 and 108.7 mg/100 g respectively. Methanolic extract containing significant amounts of phenols and flavonoids showed free radical scavenging potential and antibacterial activities against various spp. of Gram positive and Gram negative bacteria. Compounds responsible for antibacterial activities analyzed by GC-MS include beta- Sistosterol, Cholestanol, 1,5 Dibenzoylnaphthalene and 1,2-Benzenedicarboxylic acid. Flavor components extracted by hot extraction method were found to be higher in number and concentration than the cold extraction method. The characteristic flavor component of mushroom i.e. 1-Octen-3-ol was better extracted by hot than the cold. PMID- 25114339 TI - Efficacy of pink guava pulp as an antioxidant in raw pork emulsion. AB - Lipid oxidation-induced quality problems can be minimized with the use of natural antioxidants. The antioxidant potential of pink guava pulp (PGP) was evaluated at different levels (0%; C, 5.0%; T-1, 7.5%; T-2 and 10.0%; T-3) in the raw pork emulsion during refrigerated storage of 9 days under aerobic packaging. Lycopene and beta-carotene contents increased (P < 0.05) with PGP levels. The redness (a*) increased (P < 0.05), whereas L*decreased (P < 0.05) with the incorporation of PGP. The visual colour and odour scores were greater (P < 0.05) in PGP-treated products than control. Percent metmyoglobin formation was greater (P < 0.05) in the control than PGP-treated products, and increased (P < 0.05) during storage in all the treatments. Overall, peroxide value, thiobarbituric acid reactive substances and free fatty acid values were lower (P < 0.05) in PGP-treated raw emulsion than control throughout storage period. Our results indicated that pink guava pulp can be utilized as antioxidants in raw pork products to minimize lipid oxidation, off-odour development, and surface discolouration. PMID- 25114340 TI - Optimization of ingredients for noodle preparation using response surface methodology. AB - In the present investigation, the composite flour combinations using whole wheat flour (X1), tapioca flour (X2) and defatted soy flour (X3) for the noodle preparation were made through central composite rotatable design (CCRD). The analyzed responses were bulk density (BD), proximate composition, water uptake ratio (WUR), cooking volume expansion (VE), water absorption capacity (WAC), swelling capacity (SC), gruel solid loss (GSL), and sensory characteristics. A second order quadratic polynomial equation was fitted to the data of all responses for prediction. The maximum protein content of 16 g% was achieved by the combination of 75.54 g of whole wheat flour, 10 g of tapioca flour and 19.78 g of defatted soy flour. Since the inclusion of defatted soy flour >10 g resulted negative influence on good quality determining responses, the Chinese salted noodles of excellent quality with maximum WAC, WUR, VE, SC, protein, carbohydrate, ash and minimum GSL, BD, fat, moisture could be made from ratio of combination of three independent variables at 77.33 g (X1): 22.19 g (X2): 8.92 g (X3) respectively. The cost of production per kg of noodles with optimum level of ingredient was Rs.75.50/-. PMID- 25114341 TI - Study of chemical properties and evaluation of collagen in mantle, epidermal connective tissue and tentacle of Indian Squid, Loligo duvauceli Orbigny. AB - The chemical composition and evaluation of Indian squid (Loligo duvauceli) mantle, epidermal connective tissue and tentacle is investigated in this current study. It is observed that squid mantle contains 22.2% total protein; 63.5% of the total protein is myofibrillar protein. The unique property of squid myofibrillar protein is its water solubility. Squid mantle contains 12.0% total collagen. Epidermal connective tissue has highest amounts of total collagen (17.8%). SDS-PAGE of total collagen identified high molecular weight alpha-, beta and gamma- sub-chains. Amino acid profile analysis indicates that mantle and tentacle contain essential amino acids. Arginine forms a major portion of mantle collagen (272.5 g/100 g N). Isoleucine, glutamic acid and lysine are other amino acids that are found in significantly high amounts in the mantle. Sulphur containing cystine is deficit in mantle collagen. Papain digest of mantle and epidermal connective tissue is rich in uronic acid, while papain digest, collagenase digest and urea digest of epidermal connective tissue has significant amounts of sialic acid (25.2, 33.2 and 99.8 MUmol /100 g, respectively). PAS staining of papain digest, collagenase digest and urea digest also identify the association of hexoses with low molecular weight collagen fragments. Histochemical sectioning also emphasized the localized distribution of collagen in epidermal and dermal region and very sparse fibres traverse the myotome bundles. PMID- 25114342 TI - Suitability of spring wheat varieties for the production of best quality pizza. AB - The selection of appropriate wheat cultivars is an imperative issue in product development and realization. The nutritional profiling of plants and their cultivars along with their suitability for development of specific products is of considerable interests for multi-national food chains. In this project, Pizza-Hut Pakistan provided funds for the selection of suitable newly developed Pakistani spring variety for pizza production. In this regard, the recent varieties were selected and evaluated for nutritional and functional properties for pizza production. Additionally, emphasis has been paid to assess all varieties for their physico-chemical attributes, rheological parameters and mineral content. Furthermore, pizza prepared from respective flour samples were further evaluated for sensory attributes Results showed that Anmool, Abadgar, Imdad, SKD-1, Shafaq and Moomal have higher values for protein, gluten content, pelshenke value and SDS sedimentation and these were relatively better in studied parameters as compared to other varieties although which were considered best for good quality pizza production. TD-1 got significantly highest score for flavor of pizza and lowest score was observed from wheat variety Kiran. Moreover, it is concluded from current study that all wheat varieties except TJ-83 and Kiran exhibited better results for flavor. PMID- 25114343 TI - Quality indices of the set-yoghurt prepared from bovine milk treated with horseradish peroxidase. AB - Horseradish peroxidase (HRP, EC 1.11.1.7) was applied to treat whole bovine milk in the presence or absence of ferulic acid (FA). The treated milk exhibited different rheological properties from the control milk, and was used to prepare set-yoghurt with commercial direct vat set starter. Some chemical, textural and rheological properties of the yoghurt prepared were measured and compared. Compared to that prepared with the control milk, the yoghurt prepared with the HRP- or HRP and FA-treated bovine milk exhibited an increased hardness and adhesiveness, lower syneresis extent, higher apparent viscosity, and higher storage modulus and viscous modulus. Observation of the microstructure of the yoghurt samples under scanning electron microscopy illustrated that HRP treatment of bovine milk led to the prepared yoghurt a more compact and uniform structure. The results in the present work stated that treatment of bovine milk with HRP in the presence of ferulic acid could be applied to improve the quality of set yoghurt. PMID- 25114344 TI - In vitro free radical scavenging and DNA damage protective property of Coriandrum sativum L. leaves extract. AB - Coriandrum sativum L. (coriander), an everyday spice in the Indian kitchen is known to add flavor to the cuisine. It is an annual herb belonging to the Apiaceae (Umbellifera) family. The hydro-alcohol extract of Coriandrum sativum L. at the dose of 1 mg/ml was subjected to a series of in vitro assays viz. 2, 2'- diphenyl-1-picrylhydrazyl, lipid peroxidation by thiobarbituric acid, reducing power and nitric oxide (NO) radical scavenging in order to study its antioxidant efficacy in detail. The amount of flavonoids in 70% ethanol extract was found to be 44.5 MUg and that of the total phenols was 133.74 MUg gallic acid equivalents per mg extract. The extracts of the leaves showed metal chelating power, with IC50 values, 368.12 MUg/ml where as that of standard EDTA was 26.7 MUg/ml. The IC50 values for 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid radical scavenging was 222 MUg/ml where as that of standard ascorbic acid was 22.6 MUg/ml. The NO scavenging activity of the extract of the leaves showed IC50 value of 815.6 MUg/ml; at the same time the standard BHA had 49.1 MUg/ml. All the plant extracts provided DNA damage protection; however, the protection provided at the dose of 8 MUg/ml was comparable to that of standard gallic acid. The Coriandrum sativum leaf extract was able to prevent in vitro lipid peroxidation with IC50 values; 589.6 MUg/ml where as that of standard BHA was 16.3 MUg/ml. Our results also showed significant ferric reducing power indicating the hydrogen donating ability of the extract. This study indicated the potential of the leaf extract as a source of natural antioxidants or nutraceuticals that could be of use in food industry with potential application to reduce oxidative stress in living system. PMID- 25114345 TI - Drying kinetics and physico-chemical characteristics of Osmo- dehydrated Mango, Guava and Aonla under different drying conditions. AB - Mango (Mangiferra indica L), guava (Psiduim guajava L.) slices and aonla (Emblica officinalis L) segments were osmo-dried under four different dying conditions viz., cabinet drier (CD), vacuum oven drier (VOD), low temperature drier (LTD) and solar drier (SD) to evaluate the best drying condition for the fruits. It was found that vacuum oven drying was superior to other mode of drying as it holds maximum nutrients like acidity, ascorbic acid, sugar and water removal and moisture ratio of products. It was found through regression analysis that drying ratio and rehydration ratio was also superior in vacuum drying followed by cabinet drying. In addition, descriptive analysis on sensory score was also found best with vacuum drying while the Non-enzymatic browning (NEB), which is undesirable character on dried product, was more with solar drier. PMID- 25114346 TI - Antioxidant potential of thuja (Thuja occidentalis) cones and peach (Prunus persia) seeds in raw chicken ground meat during refrigerated (4 +/- 1 degrees C) storage. AB - The antioxidant activity of thuja (Thuja occidentalis) cones extract (TCE) and peach (Prunus armeniaca) seeds extract (PSE) were estimated by DPPH free radical scavenging activity method. Total phenolics, total flavonoids and reducing power were also estimated in these extracts. Antioxidant potential of these by products was also evaluated in raw chicken ground meat (GM) during refrigerated (4 +/- 1 degrees C) storage. Total phenolics in TCE and PSE were 7.80 +/- 0.04 and 1.92 +/ 0.04 mg TAE/gdw respectively. Both extract also showed remarkable DPPH radical scavenging activity (25.52 +/- 1.92% and 24.99 +/- 0.32%). The reducing powerOD700 was observed more in TCE as compared to PSE (3.32 +/- 0.01 and 0.49 +/ 0.01). Total flavonoids contents were 7.48 +/- 0.02 and 0.85 +/- 0.01 mg CE/gdw respectively. Addition of these extract significantly (P < 0.01) affected cooking losses and WHC of GM. During refrigerated storage (4 degrees C) the TBARS values at 8 d were significantly (P < 0.01) more in control than TCE and PSE treated groups. PMID- 25114347 TI - Effects of gamma irradiation and/or cooking on nutritional quality of faba bean (Vicia faba L.) cultivars seeds. AB - The effect of gamma irradiation (0.5 and 1.0 kGy) and/or cooking on the proximate composition, mineral content, tannin content, phytic acid content and the in vitro protein digestibility (IVPD) of two Sudanese faba bean cultivars (BB7-S1 and SH-S2) was investigated in the present study. The results obtained revealed that gamma irradiation and/or cooking treatments have slight effect in chemical composition and mineral content, while they caused significant (P <= 0.05) reduction on tannin content for both cultivars. Cooking of faba bean seeds also insignificantly (P <= 0.05) reduced phytic acid content for both cultivars, while irradiation process and/or cooking had fluctuated effect. For both cultivars, irradiation of seeds and/or cooking increased the in vitro protein digestibility (IVPD), with maximum value of IVPD (79.97%) obtained for cultivar BB7-S1. The results indicate that the treatments used in this study might improve the nutritive quality of faba bean seed due to reduction in antinutritional factors with a concomitant increase in IVPD. PMID- 25114348 TI - Quality of osmotically pre-treated and vacuum dried pineapple cubes on storage as influenced by type of solutes and packaging materials. AB - The quality and stability of osmotically pre-treated and subsequently vacuum dried pineapple cubes using three different solutes and packed in three different types of packaging materials on storage was evaluated. The experiment was laid out in completely randomized block design with two factors and three replications for each treatment. Treatment combinations were considered as one factor and storage interval as another factor. Pineapple cubes stored in glass bottle showed very little percentage variation in moisture content due to its high moisture barrier properties. In all treatment combination, acidity values were invariably found to increase as the storage progressed. For all three different osmotic treatments, HDPE pouch packet always showed highest acidity followed by PVDC pouch. Again among three solutes under consideration, invert sugar recorded a rapid increase in acidity than other solutes. In pineapple cubes osmotically treated with sucrose solution, the rates of decrease of total sugar content were lower than that of invert sugar and sorbitol treated pineapple cubes. The percentage decrease of total sugar content was highest when the osmotically dehydrated pineapple cubes were packed in HDPE pouch and it was least in glass bottles. There was a gradual decrease in ascorbic acid content with the extension of storage period and this decrease was statistically significant at all storage intervals up to six-month. Lowest value of ascorbic acid content (15.210 mg per 100 g initial solid) was recorded in invert sugar treated pineapple cube packed in HDPE pouch after 6 months of storage. PMID- 25114349 TI - Synbiotic yogurt-ice cream produced via incorporation of microencapsulated lactobacillus acidophilus (la-5) and fructooligosaccharide. AB - Yogurt-ice cream is a nutritious product with a refreshing taste and durability profoundly longer than that of yogurt. The probiotic Lactobacillus acidophilus (La-5) cells either in free or encapsulated form were incorporated into yog-ice cream and their survivability were studied. Fructooligosaccharide (FOS) as a prebiotic compound at three levels (0, 4 & 8 % w/w) was added to yogurt-ice cream mix and its effects on some chemical properties, overrun and firmness of product were evaluated. The higher the incorporated FOS concentration, the lower were the pH value and higher the total solid content of treatments. FOS incorporation (8 %) significantly increased the overrun of treatments and reduced their firmness. The viable counts of free probiotics decreased from ~9.55 to ~7.3 log cfu/g after 60 days of frozen storage while that of encapsulated cells merely decreased less than 1 log cycle. Encapsulation with alginate microbeads protected the probiotic cells against injuries in the freezing stage as well as, during frozen storage. PMID- 25114350 TI - Homogenate extraction of gardenia yellow pigment from Gardenia Jasminoides Ellis fruit using response surface methodology. AB - Homogenate extraction technology was developed for extraction of gardenia yellow pigment from Gardenia jasminoides Ellis fruit. The operating parameters affecting the color value of gardenia yellow pigment were studied on the basis of a Box Behnken design and response surface methodology. Results showed that the optimum extraction conditions were as follows: extraction time 41 s, ethanol concentration 50 %, ratio of liquid to material 15:1 (mL:g) and particle size 1.7 mm. Under the optimum condition, the experimental color value was 52.37 g(-1), which was in keeping with the predicted one. Compared with the heat extraction method, the color value of gardenia yellow pigment of homogenate extraction was higher and the extraction time was shorter. Homogenate extraction method is an ideal means for extraction of gardenia yellow pigment from Gardenia jasminoides Ellis fruit. PMID- 25114351 TI - Effect of different preservative treatments on the shelf-life of sorghum malt based fermented milk beverage. AB - Studies were conducted to extend the shelf life of sorghum based fermented milk beverage (referred to SSL) developed at our Institute. In the first approach preservatives namely nisin (N) @ 400RU/ml, MicroGARD (M) @ (1%), potassium sorbate (PS) @ (0.15%) were added to the beverage before packaging and in the second approach thermization (65 degrees C/5 min) of the packaged samples containing above mentioned preservatives was adopted. The shelf life was assessed on the basis of sensory, physico-chemical and microbiological parameters. Total plate count and lactic acid bacterial count increased till 7th day of storage and afterwards decreased significantly (p < 0.01). Yeasts and molds count increased significantly (p < 0.01) throughout the storage period and the rate of increase was lowest in samples containing PS. Samples containing PS, N and M were found sensorily acceptable up to 35, 28 and 21 days, respectively. Though the thermization treatment helped in improving the microbiological and chemical quality of the beverage, the sensory and physical quality was adversely affected. Addition of PS without thermization was found to be the best preservation technique for enhancing the shelf life of SSL at refrigeration conditions. PMID- 25114352 TI - Effect of cheese as a fat replacer in fermented sausage. AB - The effects of beef fat substitution with kashar cheese were studied in traditional Turkish fermented sausage; sucuk. Six sucuk formulations were prepared by replacing 0, 10, 20, 30, 40 and 50% of beef fat was substituted with kashar cheese. The fat substitution of fat with kashar cheese decreased fat content and increased protein content of the product that affected the chemical, physical and sensorial characteristics of products. Saturated fatty acid content increased and unsaturated, mono-unsaturated and poly-unsaturated fatty acids amount were decreased as the cheese amount increased. The formulation with 10% substitution of beef fat with cheese took the best sensory overall acceptability scores followed by 20% and control groups. PMID- 25114353 TI - Extracellular chitin deacetylase production in solid state fermentation by native soil isolates of Penicillium monoverticillium and Fusarium oxysporum. AB - Extracellular chitin deacetylase production by native soil isolates of Penicillium monoverticillium CFR 2 and Fusarium oxysporum CFR 8 in solid state fermentation (SSF) using commercial wheat bran (CWB) and shrimp processing by products (SPP) as solid substrate has been studied. P. monoverticillium produced maximum chitin deacetylase activity of 547.7 +/- 45 and 390.2 +/- 31 units/g initial dry substrate (U/g IDS) at 96 h of incubation in CWB and SPP media, respectively. While, F. oxysporum produced maximum chitin deacetylase activity of 306.4 +/- 22 U/g IDS at 72 h of incubation in CWB medium and 220.1 +/- 20 U/g IDS at 120 h of incubation in SPP medium. Along with chitin deacetylase, P. monoverticillium and F. oxysporum produced other chitin degrading enzymes such as endo-chitinase and beta-N-acetylhexosaminidase. P. monoverticillium produced maximum activity (U/g IDS) of endo-chitinase 4.6 +/- 0.20 at 120 h incubation and beta-N-acetylhexosaminidase 82.6 +/- 03 at 120 h incubation in CWB medium. While, F. oxysporum produced maximum activity (U/g IDS) of endo-chitinase 7.8 +/- 0.20 at 144 h incubation and beta-N-acetylhexosaminidase 38.3 +/- 02 at 120 h incubation in CWB medium. Production of extracellular chitin deacetylase by P. monoverticillium CFR 2 and F. oxysporum CFR 8 in SSF is being reported for the first time. PMID- 25114355 TI - Combined effect of ohmic heating and enzyme assisted aqueous extraction process on soy oil recovery. AB - This research describes a new technological process for soybean oil extraction. The process deals with the combined effect of ohmic heating and enzyme assisted aqueous oil extraction process (EAEP) on enhancement of oil recovery from soybean seed. The experimental process consisted of following basic steps, namely, dehulling, wet grinding, enzymatic treatment, ohmic heating, aqueous extraction and centrifugation. The effect of ohmic heating parameters namely electric field strength (EFS), end point temperature (EPT) and holding time (HT) on aqueous oil extraction process were investigated. Three levels of electric field strength (i.e. OH600V, OH750V and OH900V), 3 levels of end point temperature (i.e. 70, 80 and 90 degrees C) and 3 levels of holding time (i.e. 0, 5 and 10 min.) were taken as independent variables using full factorial design. Percentage oil recovery from soybean by EAEP alone and EAEP coupled with ohmic heating were 53.12 % and 56.86 % to 73 % respectively. The maximum oil recovery (73 %) was obtained when the sample was heated and maintained at 90 degrees C using electric field strength of OH600V for a holding time of 10 min. The free fatty acid (FFA) of the extracted oil (i.e. in range of 0.97 to 1.29 %) was within the acceptable limit of 3 % (oleic acid) and 0.5-3 % prescribed respectively by PFA and BIS. PMID- 25114354 TI - Optimization of enzymatic hydrolysis of guar gum using response surface methodology. AB - Guar gum is a polysaccharide obtained from guar seed endosperm portion. Enzymatically hydrolyzed guar gum is low in viscosity and has several health benefits as dietary fiber. In this study, response surface methodology was used to determine the optimum conditions for hydrolysis that give minimum viscosity of guar gum. Central composite was employed to investigate the effects of pH (3-7), temperature (20-60 degrees C), reaction time (1-5 h) and cellulase concentration (0.25-1.25 mg/g) on viscosity during enzymatic hydrolysis of guar (Cyamopsis tetragonolobus) gum. A second order polynomial model was developed for viscosity using regression analysis. Results revealed statistical significance of model as evidenced from high value of coefficient of determination (R(2) = 0.9472) and P < 0.05. Viscosity was primarily affected by cellulase concentration, pH and hydrolysis time. Maximum viscosity reduction was obtained when pH, temperature, hydrolysis time and cellulase concentration were 6, 50 degrees C, 4 h and 1.00 mg/g, respectively. The study is important in optimizing the enzymatic process for hydrolysis of guar gum as potential source of soluble dietary fiber for human health benefits. PMID- 25114356 TI - Effect of partial replacement of sugar with stevia on the quality of kulfi. AB - Stevia is a natural sweetener obtained from the leaf of Stevia rebaudiana plant. Its refined extract powder is 130-300 times sweeter than sucrose. Besides, it prevents diabetes, decreases weight, prevents tooth decay, increases digestion etc. Dietetic kulfi was produced, in which 50, 60 and 70% sugar was replaced with 0.05, 0.06 and 0.07% refined stevia extract powder respectively. At higher levels of sugar replacement there was a significant decrease in specific gravity, melting rate, carbohydrate percentage and total calorie content and a significant increase in freezing point, hardness and fat, protein, ash and moisture percentage. Kulfi prepared by replacing half the sugar content with stevia was adjudged on par with the control in sensory characteristics. Above 50% sugar replacement resulted in bitterness, lack of brownish appearance and presence of icy texture. PMID- 25114358 TI - Development of post-harvest protocol of okra for export marketing. AB - The study was carried out on the harvesting and handling methods of okra with the objective to maintain the best quality of pods from harvesting to end consumer especially for export marketing. For that purpose okra cv. 'Punjab-8' pods were harvested with minimum handling (least injuries to the pubescence on the ridges of pod) and normal handling (no safety taken to prevent injuries on pods). Pods were precooled at 15 +/- 1oC, 90-95% RH; jumble packed in the CFB boxes of 2.0 Kg capacity and than stored at 8 +/- 1oC, 90-95% RH. The quality parameters of okra namely texture, chlorophyll content, physiological loss in weight, rotting percentage and general appearance were studied. The pods harvested with minimum handling and field packaging can retain their green colour, crisp texture (maximum force to puncture pod = 500.2 g) with minimum rotting (3.0%) and physiological loss in weight (15.8%) and good appearance upto 13 days of cold storage whereas normal handled pods can be stored upto 5 days at 8 +/- 1oC, 90 95% RH and thereafter lost their general appearance on the 7th day of storage and were discarded. Therefore, in order to maintain high quality of okra from harvesting to the final destination (consumer), the okra pods should be harvested with minimum handling followed by field packaging in CFB boxes. PMID- 25114357 TI - Minerals and antinutrients profile of rabadi after different traditional preparation methods. AB - Rabadi is a cereal and buttermilk based traditional fermented recipe of western region of India. There are many traditional preparation methods, which may alter biochemical composition of rabadi, therefore, in the present study, role of traditional processings (cooking, fermentation, dehulling, utensil, preparation methods and cereals) on minerals and antinutrients of pearl millet, wheat flour and refined wheat flour rabadi was investigated on fresh weight basis. Results showed that the process of cooking and fermentation enhanced minerals (Ca, Fe and P) in all types of rabadi samples at different levels of significance, while antinutrients (phytic acid, total phenols and oxalates) reflected a declining trend. Intercomparison of different types of rabadies exhibited that fermented- cooked -fermented samples were better than cooked -fermented rabadies. Dehulling caused a loss of minerals, but antinutrients were also degraded after dehulling; therefore dehulled sample showed very good nutritional profile after fermentation. Earthen pot rabadi samples presented better biochemical composition than rabadies prepared in steel pot. Intercomparison of different cereals based rabadies reflected superior position of fermented -cooked- fermented pearl millet flour rabadi than cooked- fermented pearl millet flour rabadi, wheat and refined wheat flour rabadi samples. PMID- 25114359 TI - Antioxidant and antiplatlet aggregation properties of bark extracts of Garcinia pedunculata and Garcinia cowa. AB - The bark extracts of Garcinia pedunculata and Garcinia cowa, which are abundant in the Northeastern regions of India, were screened for their antioxidant and in vitro antiplatelet aggregating activities. By beta-carotene linoleate model for antioxidant assay, acetone extract of G. pedunculata and hexane extracts of G. cowa exhibited higher antioxidant activity (86.47 and 66.94 % respectively, at 25 ppm) than other extracts. Similar pattern was observed for superoxide radical scavenging method for antioxidant assay. The ethyl acetate extract of G. pedunculata and hexane extract of G. cowa exhibited higher antiplatelet aggregation capacity towards ADP induced platelet aggregation (IC50 0.16 and 0.43 ug, respectively) than other extracts. PMID- 25114360 TI - Hepatitis A virus in West Africa: Is an epidemiological transition beginning? AB - BACKGROUND: Studies of hepatitis A virus (HAV) seroprevalence in sub-Saharan Africa have generally found very high anti-HAV IgG seroprevalence rates, but economic development and improved drinking water access may be contributing to decreasing incidence. MATERIALS AND METHODS: This review evaluates all 19 articles that have been published on HAV epidemiology in West Africa. RESULTS: Nearly all studies conducted before 1990 found that the majority of preschool aged children had already developed immunity due to prior infection. However, several recent studies have observed that the age at midpoint of population immunity in some urban populations has shifted to school-aged children. CONCLUSION: There is preliminary evidence that some West-African countries are beginning the transition towards lower hepatitis A endemicity levels. Additional studies of child seroprevalence rates in diverse parts of West Africa are required in order to clarify the extent to which an early transition may be occurring. PMID- 25114361 TI - Comparison of values of traditionally measured venous bicarbonate with calculated arterial bicarbonate in intensive care unit patients of a hospital in a third world country. AB - BACKGROUND: Measurement of serum or plasma bicarbonate (HCO3 (-)) from a sample of peripheral venous blood is routinely practiced in hospital patient managements. HCO3 (-) status can also be obtained by a simple calculation during blood gas analysis requiring arterial blood as sample which is cumbersome for both patient and doctor. This study compared the measured bicarbonate levels with calculated arterial values in intensive care unit (ICU) patients to determine whether traditionally measured venous HCO3 (-) and calculated HCO3 (-) values [from arterial blood gas (ABG) analyzers] can be used interchangeably. MATERIALS AND METHODS: This prospective study was carried out at a tertiary care teaching hospital in Dhaka, the capital of Bangladesh. A total of 56 adult patients with diverse medical conditions, presenting at the ICU of the health centre were enrolled in this study when deemed by the treating physician to have an ABG analysis. Arterial and venous samples were taken as close in time as possible for gas analysis and routine blood tests. RESULTS: The HCO3 (-) levels from ABG and traditionally measured serum showed acceptably narrow 95% limits of agreement using the Bland-Altman method. CONCLUSIONS: More widely prescribed venous HCO3 ( ) measurements can also be a useful substitute for an expensive ABG analyzer in resource-constrained health care sectors when required. However, accuracy of venous blood in assessment of additional ABG parameters is yet to be discovered. PMID- 25114362 TI - Is total lymphocyte count a predictor for CD4 cell count in initiation antiretroviral therapy in HIV-infected patients? AB - BACKGROUND: Since laboratory assessments of HIV-infected patients by flow cytometric methods are expensive and unavailable in resource-limited countries, total lymphocyte count by haematology cell counter is supposed to be a suitable surrogate marker to initiate and monitor course of the disease in these patients. The aim of this study was to evaluate the utility of total lymphocyte count as a surrogate marker for CD4 count in HIV-infected patients. PATIENTS AND METHODS: In a prospective study 560 HIV-positive individuals evaluated for total and CD4 lymphocyte count. For correlation between CD4 count and total lymphocyte count, haemoglobin and haematocrit we defined cut-off values as 200 cell/MUl, 1200 cell/MUl, 12 gr/dl and 30%, respectively, and compared CD4 count with each parameter separately. Positive predictive value, negative predictive value, sensitivity and specificity of varying total lymphocyte count cutoffs were computed for CD4 count <= 200 cell/MUl and <= 350 cell/MUl. RESULTS: Strong degree of correlation was noted between CD4 and total lymphocyte count (r: 0.610, P < 0.001). Mean and standard deviation of total lymphocyte count, haemoglobin and haematocrit in relation to CD4 count were calculated which indicated significant correlation between these variables. Kappa coefficient for agreement was also calculated which showed fair correlation between CD4 200 cell/MUl and total lymphocyte count 1200 cell/MUl (0.35). CONCLUSION: This study reveals that despite low sensitivity and specificity of total lymphocyte count as a surrogate marker for CD4, total lymphocyte count is of great importance and benefit in resource-limited settings. PMID- 25114363 TI - Acceptability of HIV/AIDS testing among pre-marital couples in Iran (2012). AB - BACKGROUND: Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) is a lifestyle-related disease. This disease is transmitted through unprotected sex, contaminated needles, infected blood transfusion and from mother to child during pregnancy and delivery. Prevention of infection with HIV, mainly through safe sex and needle exchange programmes is a solution to prevent the spread of the disease. Knowledge about HIV state helps to prevent and subsequently reduce the harm to the later generation. The purpose of this study was to assess the willingness rate of couples referred to the family regulation pre-marital counselling centre for performing HIV test before marriage in Yazd. PATIENTS AND METHODS: In this descriptive study, a simple random sampling was done among people referred to Akbari clinic. The couples were 1000 men and 1000 women referred to the premarital counselling centre for pre-marital HIV testing in Yazd in the year 2012. They were in situations of pregnancy, delivery or nursing and milking. The data were analyzed using Statistical Package for the Social Sciences (SPSS) software and chi-square statistical test. RESULTS: There was a significant statistical difference between the age groups about willingness for HIV testing before marriage (P < 0.001) and also positive comments about HIV testing in asymptomatic individuals (P < 0.001). This study also proved a significant statistical difference between the two gender groups about willingness to marry after HIV positive test of their wives. CONCLUSION: The willingness rate of couples to undergo HIV testing before marriage was significant. Therefore, HIV testing before marriage as a routine test was suggested. PMID- 25114364 TI - Nodal vascularity as an indicator of cervicofacial metastasis in oral cancer: A Doppler sonographic study. AB - BACKGROUND: The objective of this study was to assess nodal vascularity by Doppler sonography and to find out the correlation between clinical and various Doppler sonographic features for the detection of the metastatic nodes in oral cancer patients. PATIENTS AND METHODS: A total number of 55 patients of histopathologically proven oral cancer presenting with enlarged superficial cervicofacial lymph nodes were included in the study. Patients were subjected to clinical examination according to a specially designed proforma and the TNM staging was done. If more than one enlarged nodes were present, then the node with the largest diameter was chosen for further Doppler ultrasonographic examination followed by fine needle aspiration cytology test of the same node. RESULTS: Correlations of patterns of color Doppler flow signals with cytological diagnosis showed that central type of vascular pattern was statistically significant parameter for benign lymph nodes and peripheral type of vascularity was highly significant parameter for malignant lymphadenopathy. It was found that the cut-off value of resistive index 0.6 was statistically significant in the assessment of metastatic node (P < 0.01) with a sensitivity of 45.5% and specificity of 93.9%. On comparison of the clinical features (TNM staging) with Doppler sonographic features, it was found that the characteristic features suggestive of malignant lymph nodes on Doppler sonography such as peripheral blood flow and high resistive index were more consistently and frequently associated with the higher sub-stages of T3 and T4 and N2b and N2c of TNM staging system. CONCLUSION: Nodal vascularity may be used to differentiate benign from malignant lymphadenopathy. Proper judicious use of non-invasive color Doppler ultrasonographic examination provides an opportunity to eliminate the need for biopsy in reactive nodes and provide treatment in a more precise manner. PMID- 25114365 TI - Respiratory symptom, lung function and exhaled carbon monoxide among a sample of traffic workers in Lagos, Nigeria: A pilot survey. AB - BACKGROUND: Traffic-related air pollution (TRAP) is a major source of air pollution but the impact on health in Nigeria is not well described. PATIENTS AND METHODS: A descriptive cross-sectional study of road traffic workers and university students in Lagos. Eligible, accessible and willing participants were included in the sample. Respiratory symptoms and anthropometry were obtained from all the participants using an adapted Medical Research Council (MRC) questionnaire and they all did a spirometry test and exhaled carbon monoxide (CO) test. RESULTS: Fifty-nine individuals participated with complete data, including 47 traffic policemen and 12 students who acted as controls. The mean age (SD) was 35.1 (8.0) and 35.4 years (6.3) for the traffic workers and students, respectively. All the respondents were men. The mean (SD) duration of occupation as a traffic policeman was 4.4 (4.4) and a median of 4 years (range 1-25). There was no significant difference in the presentation of respiratory and non respiratory symptoms between the two groups. Compared with the students, the traffic workers had higher age, height and sex adjusted forced expiratory volume in one second and forced vital capacity. Traffic policemen had significantly higher levels of exhaled CO than the students (1.18 vs 0.73 ppm, P < 0.006). CONCLUSION: There is a high prevalence of respiratory symptoms in both traffic policemen and non-traffic residents of Lagos metropolis, indicating widespread pollution. PMID- 25114366 TI - Objective structured clinical examination vs traditional clinical examination: An evaluation of students' perception and preference in a Nigerian medical school. AB - BACKGROUND: Method of testing clinical competence of medical students in this setting has been controversial. This report evaluates the perceptions and preferences of 5(th) and 6(th) year medical students about traditional clinical examination (TCE) and objective structured clinical examination (OSCE). MATERIALS AND METHODS: A cross-sectional study using a structured questionnaire, administered to 156 students, who had been previously exposed to TCE and OSCE. RESULTS: There were 110 (70.5%) males and 46 (29.5%) females, with median age group of 26-30 years. One hundred and thirty-one respondents (84%) felt TCE is more difficult and 20 (12.8%) felt OSCE was more difficult. One hundred and forty two (91%) felt OSCE was easier to pass, 8 (5.1%) felt TCE was easier to pass and 6 (3.8%) were undecided. Majority of the 5(th) and 6(th) year students (95.5% and 100%, respectively) preferred OSCE for assessment. In relation to validity and reliability of OSCE, 124 (79.5%) of all the students felt it provides a true measure of essential clinical skills, 130 (83.3%) felt its scores are standardised, 143 (91.7%) felt it is a practical and useful experience and 135 (86.5%) felt students' personality, ethnicity and gender will not affect OSCE scores. Overall, there were no significant differences in preference and perceptions between 5(th) and 6(th) year students and between males and females. CONCLUSION: Students preferred OSCE as method of assessing clinical competence and considered it a more valid and reliable method of examination. PMID- 25114367 TI - Age-predicted vs. measured maximal heart rate in young team sport athletes. AB - BACKGROUND: Although maximal heart rate (HR)max is used widely to assess exercise intensity in sport training and particularly in various team sports, there are limited data with regards to the use of age-based prediction equations of HRmax in sport populations. The aim of this study was to compare the measured-HRmax with three prediction equations (Fox-HRmax = 220-age and Tanaka-HRmax = 208 0.7*age and Nikolaidis-HRmax = 223-1.44*age) in young team sport athletes. MATERIALS AND METHODS: Athletes of soccer, futsal, basketball and water polo, classified into three age groups (u-12, 9-12 years, n = 50; u-15, 12-15 years, n = 40; u-18, 15-18 years, n = 57), all members of competitive clubs, voluntarily performed a graded exercise field test (20 m shuttle run endurance test) to assess HRmax. RESULTS: Fox-HRmax and Nikolaidis-HRmax overestimated measured HRmax, while Tanaka-HRmax underestimated it (P < 0.001). However, this trend was not consistent when examining each group separately; measured-HRmax was similar with Tanaka-HRmax in u-12 and u-15, while it was similar with Nikolaidis-HRmax in u-18. CONCLUSION: The results of this study failed to validate two widely used and one recently developed prediction equations in a large sample of young athletes, indicating the need for specific equation in different age groups. Therefore, coaches and fitness trainers should prefer Tanaka-HRmax when desiring to avoid overtraining, while Fox-HRmax and Nikolaidis-HRmax should be their choice in order to ensure adequate exercise intensity. PMID- 25114368 TI - The diagnostic value of cervicovaginal and serum ferritin levels in midgestation time to predict spontaneous preterm delivery. AB - BACKGROUND: The aim of this study was to determine diagnostic value of cervicovaginal ferretin and serum ferretin levels at midgestation time in predicting preterm delivery in singleton pregnancies. PATIENTS AND METHODS: A diagnostic test study through a prospective cohort design was carried out on 300 singleton pregnant women in 2012. A blood sample was obtained from all the patients within 22-24 gestational weeks for laboratory assessment of serum ferretin, and cervicovaginal sample was also taken to assess cervicovaginal ferritin level. Ferritin levels were compared between term and preterm deliveries at 37, 34 and 32 weeks of gestation. Receiver operating characteristics (ROC) curves were plotted to assess the diagnostic test values. RESULTS: Mean serum ferritin level was 55.38 [standard deviation (SD 23.8)] ng/mL in term deliveries versus a mean of 91.27 (SD 25.2) ng/mL in preterm deliveries, which showed a statistically significant difference (P < 0.001). The ferritin levels in cervicovaginal term delivery group had mean of 11.29 (SD 16.2) ng/mL compared with a mean of 21.95 (SD 10.1) ng/mL among those with preterm delivery before 37 weeks of gestational age(P < 0.001). The cervicovaginal ferritin level had a moderate to good diagnostic value with an area under curve being above 0.8 for all assessments. The serum ferritin level had a moderate to good diagnostic value with an area under curve being above 0.8 for all assessments. In both tests, its diagnostic value was higher for predicting preterm delivery at earlier gestational age. CONCLUSIONS: The results of this study indicate that high levels of serum and cervicovaginal ferritin in singleton pregnancies may alert the clinician of the risk of preterm delivery. Serum and cervicovaginal ferritin measurement at midgestation may be used as a predictive scale for preterm delivery in singleton pregnancies. PMID- 25114369 TI - Risk factors and drug-resistance patterns among pulmonary tuberculosis patients in northern Karnataka region, India. AB - BACKGROUND: India is one of the high tuberculosis (TB)-burden countries in the world. Resistance to anti-tuberculosis (anti-TB) drugs has already become an important and alarming threat in most of the regions worldwide. India ranks second in the world in harbouring multi-drug resistant cases (MDRTB). Prevalence of MDR-TB mirrors the functional state and efficacy of TB control programmes and realistic attitude of the community towards implementation of such programmes. The most important risk factor in the development of MDRTB is improper implementation in the guidelines in the management of TB, and high rate of defaults on the part of the patients. The study was carried out to evaluate the drug resistance pattern to first line anti-TB drugs in Northern Karnataka region, India. MATERIALS AND METHODS: A prospective study was conducted at J. N. Medical College and its associated Hospitals, Belgaum. Between January 2011 and December 2012, 150 sputum samples of suspected pulmonary TB patients based on the history were examined for the AFB culture by Lowenstein-Jensen (LJ) culture technique. A total of two early morning samples were collected for the smear [Ziehl-Neelsen (ZN) staining] and culture methods. It was observed that ZN staining for AFB was positive in 113 patients (75%), while AFB culture by LJ medium yielded growth in 66 cases (44%). Thus, a total of 66 AFB culture-positive samples by LJ medium were subjected for AFB drug-sensitivity testing (DST). DST was done for Isoniazid (INH), Rifampicin (RIF), Pyrazinamide (PZA), Ethambutol (EMB) and Streptomycin (SM) after isolation by using the resistance proportion method. RESULTS: A total of 66 AFB culture-positive specimens, 20 (30.3%) cases were sensitive to all the five drugs while 46 (69.7%) cases showed resistance to one or more drugs. Among these, the resistance to rifampicin was highest (80.4%), while resistance to isoniazid, pyrazinamide, ethambutol and streptomycin were observed to be 60%, 58.7%, 52.1% and 63%, respectively. It was also observed that, resistance to all five drugs was highest (39.18%). MDR isolates were obtained in 52.2% of the cases. Illiteracy, low socio-economic status, previous history of TB and alcoholism were found to have statistically significant association for the development of MDR. CONCLUSIONS: The prevalence of drug resistance in the present study was observed to be 69.7%. More than half of the cases were multi-drug resistant. The most common resistant pattern observed in this study was resistance to all the first-line drugs. Therefore, during initiation of new case proper explaining and completion of the treatment is very important to avoid the development of future drug resistance in the society. PMID- 25114370 TI - Early outcome of incisional hernia repair using polypropylene mesh: A preliminary report. AB - BACKGROUND: The use of prosthetics for open repair of incisional hernia is very recent in our practice. We highlight our experience repairing incisional hernias with polypropylene mesh. PATIENTS AND METHODS: Patients presenting with incisional hernia >5 cm in length or width received open polypropylene mesh repair and were followed for two years. Data obtained included age, sex, primary surgery causing the hernia, the length of the fascial defect and previous attempts at repair. Post-operative wound complications were recorded. The integrity of the scar and patient satisfaction or concerns with the repair was assessed at each visit. RESULTS: Nineteen females with a mean age of 35 years (range 30-54) underwent repair; most arising from obstetric or gynaecological procedures. Sixteen (82.2%) had midline, 2 (10.5) transverse and 1 (5.3) Pfannenstiel scars. One patient had no previous repair (R0), 7 had undergone one repair (R1), 9 had undergone two repairs (R2) and 1 had three previous repairs (R3). The length of fascial defects ranged from 8 to 18 cm and seroma collection and stitch sinus were the common problems encountered. Two (10.5%) recurrences were recorded in two years. CONCLUSION: Open mesh repair of incisional hernia carries a low risk of infection and recurrence in two years. PMID- 25114371 TI - Accuracy of subjective assessment of fever by Nigerian mothers in under-5 children. AB - BACKGROUND: Many mothers still rely on palpation to determine if their children have fever at home before deciding to seek medical attention or administer self medications. This study was carried out to determine the accuracy of subjective assessment of fever by Nigerian mothers in Under-5 Children. PATIENTS AND METHODS: Each eligible child had a tactile assessment of fever by the mother after which the axillary temperature was measured. Statistical analysis was done using SPSS version 19 (IBM Inc. Chicago Illinois, USA, 2010). RESULT: A total of 113 mother/child pairs participated in the study. Palpation overestimates fever by 24.6%. Irrespective of the surface of the hand used for palpation, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of tactile assessment were 82.4%, 37.1%, 51.9% and 71.9%, respectively. The use of the palmer surface of the hand had a better sensitivity (95.2%) than the dorsum of the hand (69.2%). The use of multiple sites had better sensitivity (86.7%) than the use of single site (76.2%). CONCLUSION: Tactile assessment of childhood fevers by mothers is still a relevant screening tool for the presence or absence fever. Palpation with the palmer surface of the hand using multiple sites improves the reliability of tactile assessment of fever. PMID- 25114372 TI - Post-graduate surgical training in Nigeria: The trainees' perspective. AB - BACKGROUND: Quality surgical training is crucial to meeting manpower needs and creating a vibrant healthcare delivery. Feedback from trainees provides insight to understanding training challenges and needs to improve the programme. The objective of this study was to determine the challenges faced by surgical trainees and their perception of their training in Nigeria. MATERIALS AND METHODS: A questionnaire survey of trainees in 16 academic surgical training centres in Nigeria between September and December 2012. RESULTS: Of 235 respondents, 227 were males (96.6%) and 8 females (3.4%) with mean age of 33.9 years. A significant proportion (62.3%) of the respondents believed that the volume and diversities of surgical cases managed during their training were sufficient; however, 53.9% were less satisfied with their operative experience. Majority (71.8%) of the respondents felt "supported" by their trainers but they also believed that the training was skewed towards service provision. They were not actively involved in research due to lack of funds in 77.7%, lack of time/motivation in 15.8%, indifference in 11.8% and poor knowledge of research methods in 9.2%. Inadequate training facilities (50.7%), poor welfare (67.2%), inadequate sponsorship (65.9%) and poor remuneration (88.3%) were identified among their challenges. On the whole, majority (62.3%) believed that their training would adequately prepare them to function independently. CONCLUSION: Surgical residents in Nigeria face a variety of challenges. Based on our findings, a training that tracks and keeps trend with global changes through a higher investment in surgical training, improved facilities and residents' well being from both the teaching authorities and government will more likely improve the quality of training. PMID- 25114373 TI - Comparison effect of intravenous tranexamic acid and misoprostol for postpartum haemorrhage. AB - BACKGROUND: Postpartum haemorrhage (PPH) is the third-most common cause of maternal death in the United States and it is still the first prevalent cause of maternal death in developing countries. Active prevention of haemorrhage with an uterotonic or other new drugs leads to a decrease in postpartum vaginal haemorrhage. The aim of this study was to compare anti-haemorrhagic effect of Tranexamic acid (TXA) and Misoprostol for PPH. PATIENTS AND METHODS: In a double blinded randomised control clinical trial, 200 women were included after Caesarean or natural vaginal delivery with abnormal PPH. They were divided into two equal intervention and control groups. Effect of intravenous TXA and Misoprostol for postpartum haemorrhage was examined. RESULTS: The mean age of patients was 26.7 +/- 6.5 years which ranged from 14 to 43 years. The sonographic gestational age in the group treated with TXA was 37.7 +/- 3.4 weeks and it was 37.4 +/- 3.3 weeks for the other group (P = 0.44). The haemorrhage in the TXA and Misoprostol groups was 1.2 +/- 0.33 litres and 1.18 +/- 0.47 litres, respectively (P = 0.79). The haemoglobin levels after 6-12 hours of labour, in TXA group was more than that of the Misoprostol group, but this difference was not statistically significant (P = 0.22 and P = 0.21, respectively). CONCLUSION: Regarding to the superior results in Misoprostol group in one hand and lack of significant differences between two groups in haemorrhage during labour, post partum haemoglobin level and discharge haemoglobin level, we can state that Misoprostol has no specific preferences to TXA, but more studies with greater population are needed. PMID- 25114374 TI - Cardiac left ventricular thrombus in protein C deficiency. AB - We report an exceptional case of, 33-year-old woman presenting with, dyspnoea and chest pain, Cardio respiratory sign and symptom related to diastolic dysfunction caused by mass effect of thrombosis on diastolic filling of left ventricule (LV). The common aetiologies of these devastating complication results in thrombophillia diagnosis, and echocardioghraphy showed a large mass in left ventricular cavity. In laboratory exam, protein C-S deficiency was confirmed however, others related test of thrombophillia were negative. The patient underwent cardiopulmonary bypass with thrombosis extraction and her sign and symptom, recovered uneventfully. This case report illustrates an exceedingly rare case of thrombophilia-induced left ventricular clot formation. PMID- 25114375 TI - Coronary artery spasm: An often overlooked diagnosis. AB - Coronary vasospasm can lead to myocardial injury and even sudden cardiac death. It has generally been overlooked as a diagnosis since atherosclerosis is a more common cause of acute coronary syndromes and because of the dilemma involved in its diagnosis. A middle-aged man with a history of smoking and cocaine use presented to the emergency department with left-sided arm/chest discomfort and diaphoresis. The electrocardiogram showed anterior ST elevation and hyper-acute T waves, which completely resolved shortly after sublingual nitroglycerin was administered. Subsequent angiogram revealed a 70% focal stenosis in the mid-left anterior descending artery. Coronary vasospasm occurs more commonly in arteries with underlying atheromatous disease, although normal vessels are not excluded. Cigarette smoking and cocaine use are among the major culprits that have been implicated as risk factors for the occurrence of coronary vasospasm. Eventually, the patient had percutaneous coronary intervention of his left-anterior descending artery and remained asymptomatic. PMID- 25114376 TI - See-saw pattern in ventilator graphic: Is there any story behind? AB - The importance of ventilator graphics cannot be over emphasized that provide the useful information about airway, ventilation, compliance and lung mechanics. Some bizarre forms of graphics are usually overlooked in view of artifacts, but sometimes these tracings may in fact predict some relevant information. PMID- 25114377 TI - Study of the correlations among some parameters of the oxidative status, gelatinases, and their inhibitors in a group of subjects with metabolic syndrome. AB - Our aim was to examine some parameters of oxidative status, gelatinases, and their inhibitors and to evaluate their interrelationships in subjects with metabolic syndrome (MS). We enrolled 65 MS subjects, subdivided according to the presence or not of diabetes mellitus. We examined lipid peroxidation (expressed as thiobarbituric acid reacting substances, TBARS), protein oxidation (expressed as carbonyl groups), nitric oxide metabolites (NO x ), total antioxidant status (TAS), MMP-2, MMP-9, TIMP-1, and TIMP-2. We found that MS subjects, diabetics and nondiabetics, showed an increase in TBARS, PC, and NO x . A significant decrease in TAS was observed only in nondiabetic MS subjects in comparison with diabetic MS subjects. We observed increased concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2, higher in diabetic subjects. Our data showed a positive correlation between TAS and MMP-2, TAS and MMP-9, and TAS and MMP-9/TIMP-1 and a negative correlation between TBARS and MMP-2 in diabetic MS subjects in the entire group. In MS subjects a prooxidant status and increased levels of gelatinases and their inhibitors are evident although the correlations between oxidative stress and MMPs or TIMPs are controversial and need further investigation. PMID- 25114378 TI - Overexpression and selectively regulatory roles of IL-23/IL-17 axis in the lesions of oral lichen planus. AB - Interleukin- (IL-) 23/IL-17 axis is a newly discovered proinflammatory signaling pathway and has been implicated in the pathogenesis of many chronic inflammatory and immune disorders. Here we investigated whether the IL-23/IL-17 axis was present and functional in the lesions of oral lichen planus (OLP), a chronic inflammatory disease affecting the oral mucosa. Using immunohistochemistry and quantitative PCR, we found that the subunits of IL-23 and IL-17 were overexpressed in OLP lesions than in normal oral mucosa tissues. In addition, the expressions of IL-23 and IL-17 are positively correlated in reticular OLP tissues. Results from in vitro studies revealed that exogenous IL-23 could increase the percentage of Th17 cells and IL-17 production in the CD4+T cells from reticular OLP patients. Furthermore, we also found that exogenous IL-17 could significantly enhance the mRNA expressions of beta-defensin-2, -3, CCL-20, IL-8, and TNF-alpha, but not beta-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6 in human oral keratinocytes. Taken together, our results revealed an overexpression pattern and selectively regulatory roles of IL-23/IL-17 axis in the OLP lesions, suggesting that it may be a pivotal regulatory pathway in the complex immune network of OLP lesions. PMID- 25114382 TI - Guest editorial. PMID- 25114381 TI - Pursuing a radiology career: Private practice or academic ? PMID- 25114379 TI - Overexpression of receptor for advanced glycation end products and high-mobility group box 1 in human dental pulp inflammation. AB - High mobility group box 1 (HMGB1), a nonhistone DNA-binding protein, is released into the extracellular space and promotes inflammation. HMGB1 binds to related cell signaling transduction receptors, including receptor for advanced glycation end products (RAGE), which actively participate in vascular and inflammatory diseases. The aim of this study was to examine whether RAGE and HMGB1 are involved in the pathogenesis of pulpitis and investigate the effect of Prevotella intermedia (P. intermedia) lipopolysaccharide (LPS) on RAGE and HMGB1 expression in odontoblast-like cells (OLC-1). RAGE and HMGB1 expression levels in clinically inflamed dental pulp were higher than those in healthy dental pulp. Upregulated expression of RAGE was observed in odontoblasts, stromal pulp fibroblasts-like cells, and endothelial-like cell lining human pulpitis tissue. Strong cytoplasmic HMGB1 immunoreactivity was noted in odontoblasts, whereas nuclear HMGB1 immunoreactivity was seen in stromal pulp fibroblasts-like cells in human pulpitis tissue. LPS stimulated OLC-1 cells produced HMGB1 in a dose-dependent manner through RAGE. HMGB1 translocation towards the cytoplasm and secretion from OLC-1 in response to LPS was inhibited by TPCA-1, an inhibitor of NF-kappaB activation. These findings suggest that RAGE and HMGB1 play an important role in the pulpal immune response to oral bacterial infection. PMID- 25114380 TI - Impaired resolution of inflammation in the Endoglin heterozygous mouse model of chronic colitis. AB - Endoglin is a coreceptor of the TGF-beta superfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated that Endoglin heterozygous (Eng (+/-)) mice subjected to dextran sulfate sodium (DSS) developed persistent gut inflammation and pathological angiogenesis. We now report that colitic Eng (+/-) mice have low colonic levels of active TGF-beta1, which was associated with reduced expression of thrombospondin-1, an angiostatic factor known to activate TGF-beta1. We also demonstrate dysregulated expression of BMPER and follistatin, which are extracellular regulators of the TGF-beta superfamily that modulate angiogenesis and inflammation. Heightened colonic levels of the neutrophil chemoattractant and proangiogenic factor, CXCL1, were also observed in DSS-treated Eng (+/-) mice. Interestingly, despite increased macrophage and neutrophil infiltration, a gut specific reduction in expression of the key phagocytic respiratory burst enzymes, NADPH oxidase 2 (Nox-2) and myeloperoxidase, was seen in Eng (+/-) mice undergoing persistent inflammation. Taken together, these findings suggest that endoglin is required for TGF-beta superfamily mediated resolution of inflammation and fully functional myeloid cells. PMID- 25114383 TI - Role of MR spectroscopy in musculoskeletal imaging. AB - Magnetic resonance spectroscopy (MRS) is an imaging approach that allows for the noninvasive molecular characterization of a region of interest. By detecting signals of water, lipids, and other metabolites, MRS can provide metabolic information for lesion characterization and assessment of treatment response. Although MRS has been routinely used in the brain, clinical applications within the musculoskeletal system have only more recently emerged. The aim of this article is to review the technical considerations for performing MRS in the musculoskeletal system, focusing on proton MRS, and to discuss its potential roles in musculoskeletal tumor imaging and the assessment of muscle physiology and disease. PMID- 25114384 TI - Peripheral nerve injury grading simplified on MR neurography: As referenced to Seddon and Sunderland classifications. AB - The Seddon and Sunderland classifications have been used by physicians for peripheral nerve injury grading and treatment. While Seddon classification is simpler to follow and more relevant to electrophysiologists, the Sunderland grading is more often used by surgeons to decide when and how to intervene. With increasing availability of high-resolution and high soft-tissue contrast imaging provided by MR neurography, the surgical treatment can be guided following the above-described grading systems. The article discusses peripheral nerve anatomy, pathophysiology of nerve injury, traditional grading systems for classifying the severity of nerve injury, and the role of MR neurography in this domain, with respective clinical and surgical correlations, as one follows the anatomic paths of various nerve injury grading systems. PMID- 25114385 TI - Bone tumor mimickers: A pictorial essay. AB - Focal lesions in bone are very common and many of these lesions are not bone tumors. These bone tumor mimickers can include numerous normal anatomic variants and non-neoplastic processes. Many of these tumor mimickers can be left alone, while others can be due to a significant disease process. It is important for the radiologist and clinician to be aware of these bone tumor mimickers and understand the characteristic features which allow discrimination between them and true neoplasms in order to avoid unnecessary additional workup. Knowing which lesions to leave alone or which ones require workup can prevent misdiagnosis and reduce patient anxiety. PMID- 25114386 TI - Imaging of articular cartilage. AB - We tried to review the role of magnetic resonance imaging (MRI) in understanding microscopic and morphologic structure of the articular cartilage. The optimal protocols and available spin-echo sequences in present day practice are reviewed in context of common pathologies of articular cartilage. The future trends of articular cartilage imaging have been discussed with their appropriateness. In diarthrodial joints of the body, articular cartilage is functionally very important. It is frequently exposed to trauma, degeneration, and repetitive wear and tear. MRI has played a vital role in evaluation of articular cartilage. With the availability of advanced repair surgeries for cartilage lesions, there has been an increased demand for improved cartilage imaging techniques. Recent advances in imaging strategies for native and postoperative articular cartilage open up an entirely new approach in management of cartilage-related pathologies. PMID- 25114388 TI - Role of ultrasound in evaluation of peripheral nerves. AB - Ultrasonography (USG) is an excellent cost-effective modality in imaging of peripheral nerves. With the newer high-frequency probes with different footprints which allow high-resolution imaging at relatively superficial location, USG can detect and evaluate traumatic, inflammatory, infective, neoplastic, and compressive pathologies of the peripheral nerves. This article describes the technique for evaluation of nerves by USG as well as the USG appearances of normal and diseased peripheral nerves. PMID- 25114387 TI - Imaging of cartilage repair procedures. AB - The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts. PMID- 25114389 TI - Comparison of conventional MRI and MR arthrography in the evaluation wrist ligament tears: A preliminary experience. AB - AIMS: To compare conventional magnetic resonance imaging (MRI) and direct magnetic resonance (MR) arthrography in the evaluation of triangular fibrocartilage complex (TFCC) and intrinsic wrist ligament tears. MATERIALS AND METHODS: T1-weighted, fat suppressed (FS) proton density plus T2-weighted (FS PD/T2), 3D multiple-echo data image combination (MEDIC) sequences and direct MR arthrography were performed in 53 patients with wrist pain. Images were evaluated for the presence and location of TFCC, scapholunate ligament (SLL) and lunatotriquetral ligament (LTL) tears, and imaging findings were compared with operative findings in 16 patients who underwent arthroscopy or open surgery (gold standard). RESULTS: SIXTEEN PATIENTS UNDERWENT ARTHROSCOPY/OPEN SURGERY: 12 TFCC tears were detected arthroscopically out of which 9 were detected on FS PD/T2 sequence, 10 on MEDIC sequence, and all 12 were detected on MR arthrography. The sensitivities of FS PD/T2, MEDIC sequences, and MR arthrography in the detection of TFCC tears were 75%, 83.3%, and 100%, respectively. Out of the eight arthroscopically confirmed SLL tears, three tears were detected on FS PD/T2 sequence, five on MEDIC sequence, and all eight were visualized on MR arthrography. The sensitivities of FS PD/T2, MEDIC sequences, and MR arthrography in detecting SLL tears were 37.5%, 62.5%, and 100%, respectively. One arthroscopically confirmed LTL tear was diagnosed on FS PD/T2 sequence, three on MEDIC sequence, and all five arthroscopically confirmed LTL tears were detected with MR arthrography. The sensitivities of PD, MEDIC sequences, and MR arthrography in detecting LTL tears were 20%, 40%, and 100%, respectively. CONCLUSIONS: MR arthrography is the most sensitive and specific imaging modality for the evaluation of wrist ligament tears. PMID- 25114390 TI - Bilateral congenital absence of flexor pollicis longus with thumb hypoplasia and thenar atrophy. AB - Congenital absence of flexor pollicis longus with or without associated anomalies of thenar muscles and thumb is of rare occurrence. Inability to flex the interphalangeal joint of the thumb and absent dorsal wrinkles and flexion creases of the thumb are important clues to the diagnosis. Routine radiography and cross sectional imaging help to confirm and document the condition. This article presents an extremely rare case of bilateral congenital absence of flexor pollicis longus tendon with thumb hypoplasia and thenar atrophy. PMID- 25114391 TI - Seronegative spondyloarthropathy-related sacroiliitis: CT, MRI features and differentials. AB - Seronegative spondyloarthropathy is a group of chronic inflammatory rheumatic diseases that predominantly affect the axial skeleton. Involvement of sacroiliac joint is considered a hallmark for diagnosis of seronegative spondyloarthropathy and is usually the first manifestation of this condition. It is essential for the radiologist to know the computed tomography (CT) and magnetic resonance imaging (MRI) features of spondyloarthropathy-related sacroiliitis as imaging plays an important role in diagnosis and evaluation of response to treatment. We present a pictorial essay of CT and MRI imaging findings in seronegative spondyloarthropathy-related sacroiliitis in various stages and highlight common differentials that need to be considered. PMID- 25114393 TI - Morel-Lavallee lesion: A closed degloving injury that requires real attention. AB - Morel-Lavallee lesions are post-traumatic, closed degloving injuries occurring deep to subcutaneous plane due to disruption of capillaries resulting in an effusion containing hemolymph and necrotic fat. Magnetic resonance imaging (MRI) is the modality of choice in the evaluation of Morel-Lavallee lesion. Early diagnosis and management is essential as any delay in diagnosis or missed lesion will lead to the effusion becoming infected or leading to extensive skin necrosis. PMID- 25114392 TI - Bone marrow lesions: A systematic diagnostic approach. AB - Bone marrow lesions on magnetic resonance (MR) imaging are common and may be seen with various pathologies. The authors outline a systematic diagnostic approach with proposed categorization of various etiologies of bone marrow lesions. Utilization of typical imaging features on conventional MR imaging techniques and other problem-solving techniques, such as chemical shift imaging and diffusion weighted imaging (DWI), to achieve accurate final diagnosis has been highlighted. PMID- 25114394 TI - MRI imaging of displaced meniscal tears: Report of a case highlighting new potential pitfalls of the MRI signs. AB - Magnetic resonance imaging (MRI) has been found to be an excellent imaging tool for meniscal injuries. Various MRI signs have been described to detect displaced meniscal injuries, specifically the bucket-handle tears. Although these signs are quite helpful in diagnosing meniscal tears, various pitfalls have also been reported for these signs. Double anterior cruciate ligament (ACL) sign refers to presence of a linear hypointense soft tissue anterior to the ACL, which represented the flipped bucket-handle tear of the meniscus. Disproportional posterior horn and flipped meniscus signs represent asymmetrically thickened horns of the menisci due to overlying displaced meniscal fragments. We report a case wherein MRI of the knee showed tear and displacement of the medial patellofemoral ligament (MPFL) and vastus medialis complex, medial collateral ligament (MCL), and posterior cruciate ligament (PCL) mimicking these signs. To our knowledge, internally displaced MPFL and MCLs have not been described as mimics for displaced meniscal fragments. PMID- 25114395 TI - Antral follicle count in normal (fertility-proven) and infertile Indian women. AB - BACKGROUND: Antral follicle count (AFC) has been labeled as the most accurate biomarker to assess female fecundity. Unfortunately, no baseline Indian data exists, and we continue using surrogate values from the Western literature (inferred from studies on women, grossly different than Indian women in morphology and genetic makeup). AIMS: (1) To establish the role of AFC as a function of ovarian reserve in fertility-proven and in subfertile Indian women. (2) To establish baseline cut-off AFC values for Indian women. SETTINGS AND DESIGN: Prospective observational case-control study. MATERIALS AND METHODS: Thirty patients undergoing workup for infertility were included and compared to equal number of controls (women with proven fertility). The basal ovarian volume and AFC were measured by endovaginal. USG the relevant clinical data and hormonal assays were charted for every patient. STATISTICAL ANALYSIS USED: SPSS platform was used to perform the Student's t-test and Mann-Whitney U-test for intergroup comparisons. Correlations were determined by Pearson's ranked correlation coefficient. RESULTS: Regression analysis revealed the highest correlation of AFC and age in fertile and infertile patients with difference in mean AFC of both the groups. Comparison of the data recorded for cases and controls showed no significant difference in the mean ovarian volume. CONCLUSIONS: AFC has the closest association with chronological age in normal and infertile Indian women. The same is lower in infertile women than in matched controls. Baseline and cut off values in Indian women are lower than that mentioned in the Western literature. PMID- 25114396 TI - Transient angioedema of small bowel secondary to intravenous iodinated contrast medium. AB - We report the clinical details and imaging findings of a case of transient angioedema of the small bowel following intravenous administration of non-ionic iodinated contrast material in a 17 year old female with no predisposing risk factors. Findings included long segment, symmetric, circumferential, low-density, bowel wall thickening involving the duodenum, jejunum, and most of the ileum on computed tomography scan obtained at 7 min following intravenous contrast material injection. This entity is self-limiting with a favourable clinical outcome and requires no specific treatment but only aggressive clinical monitoring. PMID- 25114397 TI - Imaging in emphysematous epididymo-orchitis: A rare cause of acute scrotum. AB - Emphysematous epididymo-orchitis is an uncommon, acute inflammatory process of epididymis and testis characterized by the presence of air within the tissue. Patient presents with fever, acute pain, swelling and tenderness in the scrotum. Imaging is needed for rapid accurate diagnosis and to differentiate it from other causes of acute scrotum such as testicular torsion. We report a case of emphysematous epididymo-orchitis with imaging findings on plain radiography, ultrasound, CT and MRI and a brief review of the literature. PMID- 25114398 TI - Prevalence of bombay group blood in southern bengal population. PMID- 25114399 TI - Primary hepatic lymphoma: dilemmas in diagnostic approach and therapeutic management. AB - Primary hepatic lymphoma (PHL) is a very rare malignancy and is characterized by liver involvement at presentation with no affectation of the spleen, lymph nodes, peripheral blood, bone marrow, or other tissues until at least 6 months after diagnosis. PHL should be considered in the differential diagnosis in a patient with space-occupying liver lesions and normal levels of alpha-fetoprotein and CEA. A computed tomography (CT) scan is the commonly used modality for staging lymphomas. The widespread use of positron emission tomography/CT results in the improvement in the accuracy of detecting the extent of disease, response evaluation, and prognostication. The liver biopsy, due to its pleomorphic appearances in the needle biopsy specimen, can be very challenging. Current literature favors the combination of chemotherapy as the frontline treatment for its least invasiveness and improved survival. Favorable prognosis of PHL can be obtained by early surgery combined with chemotherapy in strictly selected patients. However, the optimal therapy is still unclear and the outcomes are uncertain. PMID- 25114400 TI - Blood substitutes: possibilities with nanotechnology. AB - Nanotechnology deals with molecules in the nanometer (10(-9)) range and is currently being used successfully in the field of medicine. Nanotechnology has important implications in nearly all the branches of medicine and it has all the capabilities to revolutionize the vast field of medicine in future. Nanotechnological advancements have been used for the preparation of artificial hemoglobin. It is formed by assembling the hemoglobin molecules into a soluble complex. A recent approach includes the assembling of this artificial hemoglobin with enzymes such as catalase and superoxide dismutase into a nano-complex. This complex acts as an oxygen carrier as well as an antioxidant in conditions with ischemia-reperfusion injuries. PMID- 25114401 TI - Ocular adnexal lymphomas: report of 2 cases of mantle cell lymphomas and short review of literature. AB - Mantle cell lymphoma in ocular region is a rare phenomenon which can be either primary or secondary. Most of these cases are usually diagnosed after excisional biopsy of the involved area with first visit being in the Ophthalmology OPD. We share our experience of two such cases being referred from Ophthalmology OPD. 1st case is about a 52-year-old man who came for complaints of redness of left eye with excessive lacrimation. Examination revealed congestion of left temporal bulbar conjunctiva and a small pinkish outgrowth 2 * 2 cm adherent to temporal bulbar conjunctiva. 2nd case is a 55-year-old gentlemen who presented with complaints for 8 months duration of swelling left eyelid. Excisional biopsy and histopathological examination in both the cases were done to confirm the diagnosis. CECT head and neck were done at baseline and during follow up. These cases are being presented due to the rarity and dramatic response to chemotherapy. PMID- 25114402 TI - Platelet storage media change the expression characteristics of the platelet derived microparticles. AB - Activated platelets shed microparticles in vivo and definitely in vitro upon aging under storage. Studies about the platelet-derived microparticles (PMPs) produced in different storage media of PC were very limited. The aim of this research was to compare some surface molecules of these microvesicles in dissimilar microenvironments; plasma and the candidate medium for the platelet concentrate, Composol. Thirty units of PCs were prepared from Iranian Blood Transfusion Organization. Each unit was divided into two portions. In one of the portions, plasma was replaced with Composol using a connecting device instrument. MPs were isolated from PC and the levels of PS exposure (the annexin-binding capacity) and binding to vWF were surveyed on their surface using ELISA and flow cytometry techniques. The levels of PS exposure were increased on MPs during 7 days storage in the both media but the differences were not significant (P value >0.05). In addition, binding of PMP to vWF was declined during storage. The binding capabilities of PMP were significantly higher in Composol than that of plasma at the day 4 or 7 of storage (P value = 001). It seemed that the binding of PMPs to vWF was affected from the storage media of PC (plasma and Composol) but PS exposure was not affected from the type of storage media. PMID- 25114403 TI - Blood transfusion practice in obstetric and gynecology: impact of educational programs to create awareness for judicious use of blood components. AB - The study presents the data analysis (1) To find out the trend of blood component use during the period 2003-2010 and to determine impact of component awareness programs on reduction in whole blood (WB) and single unit transfusions. (2) To determine Hb trigger. The details about blood units issued were entered in the integrated blood bank management software as well as in Microsoft Excel. The data of 4,838 cases of pregnancy anemia; 2,244 receiving blood for obstetric (Ob) hemorrhage including 270 cases of disseminated intravascular coagulation; 1,413 women having Gynecological (Gy) bleeding; 911 Ob, 2,032 Gy and 740 surgeries for Gy malignancy were analyzed. During the years 2003-2010 there was gradual increase in component utilization for pregnancy anemia, Ob/Gy surgeries and Ob/Gy bleeding and significant reduction in WB transfusions due to component awareness programs. But single unit transfusions showed comparatively lower trend of reduction. The mean Hb was 6.4 g/dL for pregnancy anemia, 8.1 g/dL for surgeries and 7.3 g/dL for Ob/Gy bleeding. PMID- 25114404 TI - Hairy cell leukemia: clinicopathological and immunophenotypic study. AB - Hairy cell leukemia (HCL) is a rare neoplasm of mature small B lymphoid cells with characteristic circumferential 'hairy projections' involving the peripheral blood, bone marrow and splenic red pulp. With the advent of immunophenotyping and newer treatment modalities, prolonged remission can be achieved after a definitive diagnosis. Due to the rarity of this condition and presence of only a few case series from India, this work was undertaken. The aim was to study the clinico-pathologic and immunophenotypic features of all cases diagnosed as hairy cell leukemia. The cases were retrieved from Hematopathology records, between 1991 and 2012. The complete clinical details, investigations, treatment and follow-up were obtained from Medical Oncology records. The peripheral blood picture, bone marrow cytology and trephine sections along with special stains were reviewed. There were 12 cases of HCL during the study period with a M:F ratio of 11:1. Of these, ten were diagnosed as classical HCL and two as variant HCL. The most common clinical manifestations were fever, easy fatigability and weakness. Splenomegaly was present in 81.8 % cases. Though all the patients showed some form of cytopenia, there were three (25 %) patients with leucocytosis. The smears from all patients showed atypical lymphoid cells with circumferential hairy projections. TRAP was positive in 9 patients (81.8 %). Immunophenotyping was done in six cases, four were confirmed as HCL and two were diagnosed as HCL-v. The patients treated with Cladribine generally had a good response. The characteristic morphology of the hairy cells; along with correlation with the clinical features, TRAP positivity and immunophenotyping by flow cytometry is essential for diagnosis. Treatment response with Cladribine is good and has prolonged remission rates. PMID- 25114405 TI - Frequency of alloantibodies among chronic renal failure patients in red sea state. AB - Chronic renal failure patients need regular blood transfusion support to treat anemia and the development of erythrocyte alloantibodies complicates transfusion therapy. The aim of this study was to determine the frequency and specificity of alloantibodies against red cell antigens in CRF patients. This was a descriptive cross-sectional study done in the blood bank, Port Sudan, during the period of May-September 2012. A total of 84 patients (58 male and 26 female) with CRF who received at least one unit of RBC matched for ABO & Rh(D) antigens only were enrolled. Sera were screened for the presence of alloantibody by antibody screening test. The positive samples were subjected for antibody identification. The incidence of alloantibody among CRF patients was 13.1 % and the most common alloantibodies were Anti-c (27.3 %), anti-C (18.2 %), and anti-K (18.2 %). The risk of alloimmunization among CRF patients was 4.8 % with the frequency of 13.1 % and Anti-c being the commonest alloantibodies identified. PMID- 25114406 TI - Epstein-Barr Viral Load is Associated to Response in AIDS-Related Lymphomas. AB - AIDS-related lymphoma (ARL) development is associated to immunodeficiency state with proliferation of B-cells driven by HIV itself and EBV infection. However, Epstein-Barr DNA is not detected in malignant cells of all ARL subtypes. A prospective and controlled study to analyze EBV viral load (VL) in plasma and peripheral blood mononuclear cells (PBMC) of ARL patients was performed to analyze if Epstein-Barr VL could be related to response in these patients. Fifteen patients with ARL were included in this study with measurement of EBV VL at three different periods of time: at lymphoma diagnosis, upon completion of chemotherapy, and 3 months after. Two control groups composed by HIV-negative and HIV-positive patients were also evaluated for EBV VL comparison. In situ hybridization for EBER was performed on diagnostic samples of all ARL patients. Median EBV VL in PBMC and plasma had a significant decrease (p = 0.022 and p = 0.003, respectively) after ARL treatment. EBER was positive in 7 (46.7 %) cases. Median EBV VL in PBMC before lymphoma treatment in patients positive for EBER was significantly higher compared to EBER negative cases (p = 0.041). Reduction of EBV viral load during treatment of lymphoma could be predictive of response. EBER expression was associated to advanced stages of disease and worse immune status. Our study suggests that measurement of EBV VL during ARL treatment could be used as a marker for response, but further studies are needed to validate this association. PMID- 25114407 TI - Pleural effusion as an unusual initial presentation of acute myeloid leukemia. AB - Pleural effusions in acute myeloid leukemia (AML) can have wide differential diagnosis, however AML presenting as pleural effusion with leukemic infiltration is rarely documented. A 22 year old male presented with pleural effusion for 3 months and subsequently diagnosed as AML M2, which prompted us for this communication. PMID- 25114408 TI - Rare case of acquired haemophilia and lupus anticoagulant. AB - Acquired haemophilia or factor VIII (FVIII) deficiency, caused by FVIII inhibitor antibodies, is a very rare condition that commonly results in severe haemorrhagic complications. We report a case of acquired haemophilia presenting with multiple bluish patches affecting face, neck, upper & lower limbs, history of gum bleeding and left knee haemarthrosis. The patient was found to have acquired FVIII inhibitor and lupus anticoagulant (LAC). The simultaneous presence of LAC and FVIII inhibitor is exceedingly rare. The differentiation between these two conditions is crucial, because both result in a prolongation of the activated partial thromboplastin time test, which does not correct when mixed with the plasma of a normal control; however, the clinical manifestations range from thrombosis in the presence of LAC to massive haemorrhage with FVIII inhibitors. PMID- 25114409 TI - Pseudo chediak-higashi granules in acute lymphoblastic leukemia: a rare entity. AB - Pseudo-Chediak-Highashi granules are giant cytoplasmic inclusions commonly encountered in myeloblasts or other myeloid precursors in acute myeloid leukemia and myelodysplastic syndromes. They derive their name from the inherited Chediak Higashi syndrome that presents with oculocutaneous albinism, chronic infections and platelet dense granule deficiency. We report possibly the third case in world literature where these granules were seen in the blast cells of acute lymphoblastic leukemia in a 15-year-old male. PMID- 25114410 TI - Hemophagocytic lymphohistiocytosis. AB - Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder characterized by uncontrolled inflammation due to defective immune response. It may be familial or acquired, but both share a common feature of threatening the life of a patient and may lead to death unless treated by appropriate treatment. Here in we report a case of adult HLH. PMID- 25114411 TI - A rare case of anti-jk3 antibody detected on pre-transfusion investigation. AB - We report a 47-year-old Malay lady, para 4 + 1, with known medical history of hypertension whom presented at Emergency Department with severe anaemia, most likely secondary to menorrhagia caused by uterine fibroids. Her haemoglobin was 5.5 g/dl and she was transfused with three units of packed cell without any adverse reaction, her haemoglobin level increased to 9.8 g/dl. She was then planned for total abdominal hysterectomy and bilateral salpingo-oophorectomy later. Four months later when she came for the elective surgery, her pre transfusion investigations showed blood group as B Rh D positive, with a probable R1R1 phenotype. Her antibody screening was positive in all the three panel cells. Further testings showed a negative Direct Coomb's test and negative autocontrol, antibody identification showed pan-agglutination reaction on all 11 panel cells with enzyme enhancement. Patient's red cell phenotype was Jk(a-b-). Anti-Jk3 was suspected and further confirmed in the reference laboratory by phenotyping as well as negative urea lysis test. This case report highlights an extremely rare but clinically significant anti-JK3 antibody detected during pretransfusion testing. This phenotype is rare in the white population, more commonly seen in various polynesians. Increased awareness among the blood bank personnel regarding the variability of the blood group phenotype and the capricious nature of the Kidd antibodies may contribute to the better management of these patients. PMID- 25114412 TI - Chronic idiopathic non-cirrhotic portal vein thrombosis treated with a mesocaval shunt procedure and anticoagulation. AB - Portal vein thrombosis (PVT) was first reported in 1868 by Balfour and Stewart and is a medical condition in which the lumen of the portal vein is completely or partially obstructed due to the presence of a thrombus [1]. Inherited (Factor V Leiden and Prothrombin gene mutation G201210A, Protein C, S and Anti thrombin III deficiency) and acquired thrombophilias (Lupus Anticoagulant, myeloproliferative diseases, malignancy, surgery and trauma) account for majority of the cases of PVT. PMID- 25114413 TI - Platelet satellitism: a rare, interesting, in vitro phenomenon. AB - Platelet satellitism is a unique, uncommon, in vitro phenomenon seen in peripheral blood smears prepared from EDTA-mixed blood. This is seen in the form of platelets adhering to polymorphonuclear leucocytes imparting a rosette-like appearance. There is no definite causal association with any disease. The cause may be immunological or non-immunological. Severe rosetting may lead to a misdiagnosis of thrombocytopenia unless peripheral smears are examined. Here, we describe a case of incidentally detected platelet satellitism in a healthy 48 year old male subject during a routine check-up. PMID- 25114414 TI - Fascia lata allograft bridging of a rotator cuff tear in a rabbit animal model. AB - PURPOSE: Despite advances in surgical treatment options, large rotator cuff (r-c) tears still represent a challenge for orthopedic surgeons. The purpose of this study was to evaluate the temporary and spatial histological incorporation of fascia lata allografts, used for bridging artificially created defects of the r c. MATERIALS AND METHODS: Seventy-two rabbits were divided into two groups and a supraspinatus tendinous defect was created. Half of the rabbit population underwent repair only, while in the other half, the defect was bridged utilizing fascia lata allograft. The animals were euthanized at 2, 4, and 6 weeks postoperative. Half of the specimens were evaluated histologically and the other half underwent mechanical testing. RESULTS: There was an increased remodeling activity, fibroblastic in growth and strong presence of collagen fibers observed at 6 weeks on both groups. A gradually increasing mechanical strength was noticed by week 6 and increased toughness was also found at the same time period. There was no significant difference observed between the two groups regarding their histological and mechanical properties. CONCLUSIONS: In the difficult scenario of a large irreparable tear where the simple suture of the remaining r-c is impossible, allograft bridging, could be used with satisfactory results. CLINICAL RELEVANCE: Treatment Study, Level 1. PMID- 25114415 TI - Complications after subpectoral biceps tenodesis using a dual suture anchor technique. AB - PURPOSE: A variety of fixation techniques for subpectoral biceps tenodeses have been described including interference screw and suture anchor fixation. Biomechanical data suggests that dual suture anchor fixation has equivalent strength compared to interference screw fixation. The purpose of the study is to determine the early complication rate after subpectoral biceps tenodesis utilizing a dual suture anchor technique. MATERIALS AND METHODS: A total of 103 open subpectoral biceps tenodeses were performed over a 3-year period using a dual suture anchor technique. There were 72 male and 31 female shoulders. The average age at the time of tenodesis was 45.5 years. 41 patients had a minimum of 6 months clinical follow-up (range, 6 to 45 months). The tenodesis was performed for biceps tendonitis, superior labral tears, biceps tendon subluxation, biceps tendon partial tears, and revisions of prior tenodeses. RESULTS: There were a total of 7 complications (7%) in the entire group. There were 4 superficial wound infections (4%). There were 2 temporary nerve palsies (2%) resulting from the interscalene block. One patient had persistent numbness of the ear and a second patient had a temporary phrenic nerve palsy resulting in respiratory dysfunction and hospital admission. One patient developed a pulmonary embolism requiring hospital admission and anticoagulation. There were no hematomas, wound dehiscences, peripheral nerve injuries, or ruptures. In the sub-group of patients with a minimum of 6 months clinical follow-up, the only complication was a single wound infection treated with oral antibiotics. CONCLUSIONS: Subpectoral biceps tenodesis utilizing a dual suture anchor technique has a low early complication rate with no ruptures or deep infections. The complication rate is comparable to those previously reported for interference screw subpectoral tenodesis and should be considered as a reasonable alternative to interference screw fixation. LEVEL OF EVIDENCE: Level IV-Retrospective Case Series. PMID- 25114416 TI - Sudden severe postoperative dyspnea following shoulder surgery: Remember inadvertent phrenic nerve block due to interscalene brachial plexus block. AB - Advanced imaging techniques, improved operative techniques, and instrumentation combined with better patient awareness and expectations have resulted in an exponential increase in upper limb surgical procedures during recent times. Surgical teams expect superior analgesia and regional blocks have matched these expectations quite often resulting in improved patient satisfaction and early rehabilitation to achieve best results. Ultrasound-guided interscalene brachial plexus block (ISB) is commonly used to provide analgesia for procedures involving shoulder girdle. We report a case of symptomatic hemi-diaphragmatic paresis (HDP) due to the phrenic nerve block following ISB for arthroscopic sub-acromial decompression of the shoulder presenting as severe postoperative dyspnea. There is strong evidence of HDP following ISB in anesthetic literature, but not reported in related surgical specialties such as orthopedics. We wish to inform upper-limb surgeons and educate junior doctors and other ancillary staff working in upper-limb units to be aware of this serious but reversible complication. PMID- 25114417 TI - Osteochondral humeral head fracture after posterior shoulder subluxation: A case report. AB - Traumatic posterior shoulder subluxations are rare entities which require clinical suspicion upon presentation. Although literature presents many sequels of posterior shoulder subluxations, we have not come across any shearing type osteochondral fracture in the literature. In this case report we present diagnosis, treatment and follow-up results of this rare fracture in a 26-year-old male following a fall from a motorcycle. PMID- 25114418 TI - An unusual cause of mass in the shoulder: A primary hydatid cyst. AB - A hydatid cyst is a zoonotic infection which may affect any organ and tissue, particularly the liver and the lung. Primary muscular hydatid cysts comprise less than 0.7-3% of the cases. The hydatid cysts must be kept in mind to avoid a diagnostic puncture in cystic lesions to avoid the spreading of the disease. In this case report, we present an exceptionally rare case with an unusual localization of a primary hydatid cyst in the left deltoid muscle. PMID- 25114419 TI - Myositis ossificans of the humeral insertion of pectoralis major. AB - We report on a rare case of myositis ossificans of the humeral insertion of pectoralis major muscle following a single episode of trauma which, to our knowledge, has not previously been documented. PMID- 25114420 TI - What's new in emergencies, trauma, and shock? Heparin in severe traumatic brain injury: Beyond venous thromboembolism prevention? PMID- 25114421 TI - Early initiation of prophylactic heparin in severe traumatic brain injury is associated with accelerated improvement on brain imaging. AB - BACKGROUND: Venous thromboembolic prophylaxis (VTEp) is often delayed following traumatic brain injury (TBI), yet animal data suggest that it may reduce cerebral inflammation and improve cognitive recovery. We hypothesized that earlier VTEp initiation in severe TBI patients would result in more rapid neurologic recovery and reduced progression of brain injury on radiologic imaging. STUDY DESIGN: Medical charts of severe TBI patients admitted to a level 1 trauma center in 2009 2010 were queried for admission Glasgow Coma Scale (GCS), head Abbreviated Injury Scale, Injury Severity Score (ISS), osmotherapy use, emergency neurosurgery, and delay to VTEp initiation. Progression (+1 = better, 0 = no change, -1 = worse) of brain injury on head CTs and neurologic exam (by bedside MD, nurse) was collected from patient charts. Head CT scan Marshall scores were calculated from the initial head CT results. RESULTS: A total of 22, 34, and 19 patients received VTEp at early (<3 days), intermediate (3-5 days), and late (>5 days) time intervals, respectively. Clinical and radiologic brain injury characteristics on admission were similar among the three groups (P > 0.05), but ISS was greatest in the early group (P < 0.05). Initial head CT Marshall scores were similar in early and late groups. The slowest progression of brain injury on repeated head CT scans was in the early VTEp group up to 10 days after admission. CONCLUSION: Early initiation of prophylactic heparin in severe TBI is not associated with deterioration neurologic exam and may result in less progression of injury on brain imaging. Possible neuroprotective effects of heparin in humans need further investigation. PMID- 25114422 TI - Acute Flaccid paralysis in adults: Our experience. AB - Acute flaccid paralysis (AFP) is a complex clinical syndrome with a broad array of potential etiologies that vary with age. We present our experience of acute onset lower motor neuron paralysis. MATERIALS AND METHODS: One hundred and thirty three consecutive adult patients presenting with weakness of duration less than four weeks over 12 months period were enrolled. Detailed history, clinical examination, and relevant investigations according to a pre-defined diagnostic algorithm were carried out. The patients were followed through their hospital stay till discharge or death. RESULTS: The mean age was 33.27 (range 13-89) years with male preponderance (67.7%). The most common etiology was neuroparalytic snake envenomation (51.9%), followed by Guillain Barre syndrome (33.1%), constituting 85% of all patients. Hypokalemic paralysis (7.5%) and acute intermittent porphyria (4.5%) were the other important conditions. We did not encounter any case of acute polio mylitis in adults. In-hospital mortality due to respiratory paralysis was 9%. CONCLUSION: Neuroparalytic snakebite and Guillain Barre syndrome were the most common causes of acute flaccid paralysis in adults in our study. PMID- 25114423 TI - Ultrasound: A novel tool for airway imaging. AB - CONTEXT: The scope of ultrasound is emerging in medical science, particularly outside traditional areas of radiology practice. AIMS: We designed this study to evaluate feasibility of bedside sonography as a tool for airway assessment and to describe sonographic anatomy of airway. SETTINGS AND DESIGN: A prospective, clinical study. MATERIALS AND METHODS: We included 100 adult, healthy volunteers of either sex to undergo airway imaging systemically starting from floor of the mouth to the sternal notch in anterior aspect of neck by sonography. RESULTS: We could visualize mandible and hyoid bone as a bright hyperechoic structure with hypoechoic acoustic shadow underneath. Epiglottis, thyroid cartilage, cricoid cartilage, and tracheal rings appeared hypoechoic. Vocal cords were visualized through thyroid cartilage. Interface between air and mucosa lining the airway produced a bright hyperechoic linear appearance. Artifacts created by intraluminal air prevented visualization of posterior pharynx, posterior commissure, and posterior wall of trachea. CONCLUSIONS: Ultrasound is safe, quick, noninvasive, repeatable, and bedside tool to assess the airway and can provide real-time dynamic images relevant for several aspects of airway management. PMID- 25114424 TI - Arrival time pattern and waiting time distribution of patients in the emergency outpatient department of a tertiary level health care institution of North India. AB - BACKGROUND: Emergency Department (ED) of tertiary health care institute in India is mostly overcrowded, over utilized and inappropriately staffed. The challenges of overcrowded EDs and ill-managed patient flow and admission processes result in excessively long waits for patients. AIM: The objective of the present study was to analyze the patient flow system by assessing the arrival and waiting time distribution of patients in an Emergency out Patient Department (EOPD). MATERIALS AND METHODS: This short cross-sectional descriptive study was conducted in the EOPD of a Tertiary level health care Institution in North India in the month of May, 2011. The data was obtained from 591 patients, who were present in the EOPD during the month of May, 2011. The waiting time, inter arrival time between two consecutive patients were calculated in addition to the daily census data (discharge rate, admission rate and transfer out rates etc.) of the emergency. RESULTS: Arrival time pattern of patients in the EOPD was highly stochastic with the peak arrival hours to be 9.00-12.00 h in which around 26.3% patients arrived in the EOPD. The primary waiting areas of patients included patients under observation (29.6%); waiting for routine diagnostic tests (16.4%) and waiting for discharge (14.6%). Around 71% patients were waiting due to reasons within emergency complex. CONCLUSION: The patient flow of the ED could only be addressed by multifaceted, multidisciplinary and hospital wide approach. PMID- 25114425 TI - Awareness about basic life support and emergency medical services and its associated factors among students in a tertiary care hospital in South India. AB - BACKGROUND: The knowledge and skills about the basic life support (BLS) and the advanced life support are the most important determining factors of the cardiopulmonary resuscitation (CPR) success rates. OBJECTIVES: To determine the level of awareness on BLS and skills among undergraduate and postgraduate students of medical and dental profession, as well as nursing students and interns in a tertiary care hospital. MATERIALS AND METHODS: This descriptive cross-sectional study was conducted in a tertiary care hospital in South India. The awareness level on BLS and factors associated which include age, sex, level of training (undergraduate, internship, and postgraduate groups), course of study (nursing, dental, and medical groups), and previous exposure to BLS were assessed by using a structured questionnaire. The association of these variables with awareness level was assessed by independent t test, analysis of variance, and linear regression analysis. RESULTS: Among 520 study subjects, 229 were students, 171 were interns, and 120 were postgraduate students. The overall mean score of awareness was 4.16 +/- 1.40 (score range: 0-10). Age, sex, level of training, course of study, and previous exposure to BLS were significantly associated with awareness level in univariate analysis (P < 0.05). Linear regression model also showed that all the above variables were significantly associated with awareness level (P < 0.05). About 322 (61.9%) subjects attributed lack of awareness about BLS to lack of available professional training. About 479 (92.1%) responded that BLS training should be a part of medical curriculum. CONCLUSION: Awareness level on BLS is below average indicating the importance of professional training at all levels in a tertiary care health institution. PMID- 25114426 TI - Management of isolated sternal fractures using a practical algorithm. AB - BACKGROUND: The implementation of seat belt legislation has led to an increase in the frequency of isolated sternal fractures (ISFs) in motor vehicle crash. AIMS: We reviewed retrospectively the medical records of our tertiary center in order to find out the frequency of ISFs, review our experience in their management, and define the mean length of hospitalization. MATERIALS AND METHODS: From January 2008 to April 2012, 64 patients were admitted to the accident and emergency department of the University Hospital of Larissa, Greece, suffering from sternal fractures (SFs). Of these 64 patients, 45 had sustained ISF, while the remaining 19 had SF and additional injuries (intrathoracic and extrathoracic). The files of these 45 patients were further investigating as concerning the mechanism of injury, hospitalization days, morbidity, and mortality. RESULTS: All the patients had been involved in motor vehicle crashes and most of them were wearing seat belts during the accident (91%). The hospital length of stay (LOS) was 1.85 +/- 1.67. All the patients had upon admission chest radiograms, serial electrocardiographs (ECGs), echocardiograms, and cardiac enzyme levels. Two patients had abnormal ECG and abnormal cardiac enzymes which contributed in prolonged hospitalization. However, there was no incidence of cardiac complications or deaths. CONCLUSIONS: ISFs, with normal electrocardiogram, cardiac enzymes, and chest X-ray in the absence of complications, require no further investigation. PMID- 25114427 TI - Epidemiology of trauma in an acute care hospital in Singapore. AB - BACKGROUND: Trauma injury is the leading cause of mortality and hospitalization worldwide and the leading cause of potential years of productive life lost. Patients with multiple injuries are prevalent, increasing the complexity of trauma care and treatment. Better understanding of the nature of trauma risk and outcome could lead to more effective prevention and treatment strategies. MATERIALS AND METHODS: A retrospective review of 1178 trauma patients with Injury Severity Score (ISS) >= 9, who were admitted to the Acute and Emergency Care of an acute care hospital between January 2011 and December 2012. The statistical analysis included calculation of percentages and proportions and application of test of significance using Pearson's chi-square test or Fisher's exact test where appropriate. RESULTS: Over the study period, 1178 patients were evaluated, 815 (69.2%) males and 363 (30.8%) females. The mean age of patients was 52.08 +/- 21.83 (range 5-100) years. Falls (604; 51.3%) and road traffic accidents (465; 39.5%) were the two most common mechanisms of injury. Based on the three most common mechanisms of injury, i.e. fall on the same level, fall from height, and road traffic accident, the head region (484; 45.40%) was the most commonly injured in the body, followed by lower limbs (377; 35.37%) and thorax (299; 28.05%). CONCLUSION: Fall was the leading cause of injury among the elderly population with road traffic injuries being the leading cause among the younger group. There is a need to address the issues of injury control and prevention in these areas. PMID- 25114428 TI - Occupational health surveillance: Pulmonary function testing in emergency responders. AB - Emergency responders may be exposed to a variety of fumes, gases, and particulates during the course of their job that can affect pulmonary function (PF) and require the use of respiratory protection. This investigation used occupational health monitoring examination data to characterize PF in a population currently employed as emergency responders. PF tests for workers who required health examinations to ensure fitness for continued respirator use were compared to the National Health and Nutrition Examination Survey (NHANES) III Raw Spirometry database to determine if decreased PF was associated with employment as an emergency responder. The results of this research indicated that the emergency responders experienced a modest, but statistically significant, increase in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) mean values over the NHANES III population in both total and stratified analyses, including stratification by age, gender, height, and smoking history. Results are likely due to a combination of effectively controlled exposures in the workplace, and the healthy worker effect among long-term workers. PF testing required by the Occupational and Safety Health Administration (OSHA) has substantial utility for conducting occupational surveillance at the population level. In this investigation, we were able to quickly evaluate if abnormal PF existed in an industrial sector known to have exposures that, when uncontrolled, can lead to PF impairment. PMID- 25114429 TI - Procedural sedation for pediatric patients in the emergency department at King Khalid University Hospital, Riyadh, K.S.A. AB - Procedural sedation and analgesia (PSA) has become the standard of care for diagnostic and therapeutic procedures undertaken in the Emergency Department (ED). In the Pediatric Emergency Department (PED) of King Khalid University Hospital (KKUH), which is a major teaching hospital in Riyadh Kingdom of Saudi Arabia we developed a standard protocol for PSA since 2005. The aim of this article is to report the experience at KKUH in pediatric PSA. OBJECTIVES: To report the experience at KKUH in pediatric PSA. OBJECTIVES: To report the experience at KKUH in pediatric PSA. MATERIALS AND METHODS: Retrospective cross sectional study of all cases who underwent PSA for painful procedures in Pediatric Emergency at KKUH from December 2005 to July 2008. RESULTS: A total of 183 patients were reviewed. 179 patients were analyzed. Age ranges from 4 months to 13 years (mean 6 years). Nearly 66% were male. Ketamine was the most commonly used drug. Reduction of fracture/dislocation was the most common indication for sedation. Adverse events were identified in only 5.6% of patients. Vomiting was the most common recorded side-effect. The length of stay in the ED was ranging from 28 to 320 min (mean 111 min). CONCLUSION: Intravenous Ketamine is a consistently effective method of producing a rapid, brief period of adequate sedation and analgesia in children in the ED with no major side-effects noted in our experience. PMID- 25114430 TI - Effects of aminoguanidine, a potent nitric oxide synthase inhibitor, on myocardial and organ structure in a rat model of hemorrhagic shock. AB - BACKGROUND: Nitric oxide (NO) has been shown to increase following hemorrhagic shock (HS). Peroxynitrite is produced by the reaction of NO with reactive oxygen species, leads to nitrosative stress mediated organ injury. We examined the protective effects of a potent inhibitor of NO synthase, aminoguanidine (AG), on myocardial and multiple organ structure in a rat model of HS. MATERIALS AND METHODS: Male Sprague Dawley rats (300-350 g) were assigned to 3 experimental groups (n = 6 per group): (1) Normotensive rats (N), (2) HS rats and (3) HS rats treated with AG (HS-AG). Rats were hemorrhaged over 60 min to reach a mean arterial blood pressure of 40 mmHg. Rats were treated with 1 ml of 60 mg/kg AG intra-arterially after 60 min HS. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30 min to restore normo-tension. Biopsy samples were taken for light and electron microscopy. RESULTS: Histological examination of hemorrhagic shocked untreated rats revealed structural damage. Less histological damage was observed in multiple organs in AG-treated rats. AG treatment decreased the number of inflammatory cells and mitochondrial swollen in myocardial cells. CONCLUSION: AG treatment reduced microscopic damage and injury in multiple organs in a HS model in rats. PMID- 25114431 TI - The 2014 Academic College of Emergency Experts in India's Education Development Committee (EDC) White Paper on establishing an academic department of Emergency Medicine in India - Guidelines for Staffing, Infrastructure, Resources, Curriculum and Training. AB - Emergency medicine services and training in Emergency Medicine (EM) has developed to a large extent in developed countries but its establishment is far from optimal in developing countries. In India, Medical Council of India (MCI) has taken great steps by notifying EM as a separate specialty and so far 20 medical colleges have already initiated 3-year training program in EM. However, there has been shortage of trained faculty, and ambiguity regarding curriculum, rotation policy, infrastructure, teachers' eligibility qualifications and scheme of examination. Academic College of Emergency Experts in India (ACEE-India) has been a powerful advocate for developing Academic EM in India. The ACEE's Education Development Committee (EDC) was created to chalk out guidelines for staffing, infrastructure, resources, curriculum, and training which may be of help to the MCI and the National Board of Examinations (NBE) to set standards for starting 3 year training program in EM and develop the departments of EM as centers of quality education, research, and treatment across India. This paper has made an attempt to give recommendations so as to provide a uniform framework to the institutions, thus guiding them towards establishing an academic Department of EM for starting the 3-year training program in the specialty of EM. PMID- 25114432 TI - Establishing consensus on the definition of an isolated hip fracture for trauma system performance evaluation: A systematic review. AB - BACKGROUND: Risk-adjusted mortality is widely used to benchmark trauma center care. Patients presenting with isolated hip fractures (IHFs) are usually excluded from these evaluations. However, there is no standardized definition of an IHF. We aimed to evaluate whether there is consensus on the definition of an IHF used as an exclusion criterion in studies evaluating the performance of trauma centers in terms of mortality. MATERIALS AND METHODS: We conducted a systematic review of observational studies. We searched the electronic databases MEDLINE, EMBASE, BIOSIS, The Cochrane Library, CINAHL, TRIP Database, and PROQUEST for cohort studies that presented data on mortality to assess the performance of trauma centers and excluded IHF. A standardized, piloted data abstraction form was used to extract data on study settings, IHF definitions and methodological quality of included studies. Consensus was considered to be reached if more than 50% of studies used the same definition of IHF. RESULTS: We identified 8,506 studies of which 11 were eligible for inclusion. Only two studies (18%) used the same definition of an IHF. Three (27%) used a definition based on Abbreviated Injury Scale (AIS) Codes and five (45%) on International Classification of Diseases (ICD) codes. Four (36%) studies had inclusion criteria based on age, five (45%) on secondary injuries, and four (36%) on the mechanism of injury. Eight studies (73%) had good overall methodological quality. CONCLUSIONS: We observed important heterogeneity in the definition of an IHF used as an exclusion criterion in studies evaluating the performance of trauma centers. Consensus on a standardized definition is needed to improve the validity of evaluations of the quality of trauma care. PMID- 25114434 TI - Newer nonconventional modes of mechanical ventilation. AB - The conventional modes of ventilation suffer many limitations. Although they are popularly used and are well-understood, often they fail to match the patient based requirements. Over the years, many small modifications in ventilators have been incorporated to improve patient outcome. The ventilators of newer generation respond to patient's demands by additional feedback systems. In this review, we discuss the popular newer modes of ventilation that have been accepted in to clinical practice. Various intensive care units over the world have found these modes to improve patient ventilator synchrony, decrease ventilator days and improve patient safety. The various modes discusses in this review are: Dual control modes (volume assured pressure support, volume support), Adaptive support ventilation, proportional assist ventilation, mandatory minute ventilation, Bi level airway pressure release ventilation, (BiPAP), neurally adjusted ventilatory assist and NeoGanesh. Their working principles with their advantages and clinical limitations are discussed in brief. PMID- 25114433 TI - Surgical management in treatment of Jehovah's witness in trauma surgery in Indian subcontinent. AB - The Jehovah's Witness religion is a Christian movement, founded in the US in the 1870s, with 7 million followers worldwide with only 0.002% in India. There is minimal to complete absence of awareness about the existence of this community in our society. Astonishing is that fact that among medical professionals, there is almost no awareness about this unique population, regarding the fact that they completely refuse of blood transfusion even if it leads to their death. This is integral to their faith. Besides legal and ethical issues in treating these group of patients, the biggest challenge exist even in the western world is their management in trauma scenario where few options exist. We have discussed the issues and recommendations in management in trauma scenario in our Indian subcontinent. PMID- 25114436 TI - Operative management of splenic injury in a patient with proteus syndrome. AB - A 20-year-old female with Proteus syndrome sustained splenic injury after fall from a bike. She was initially managed non-operatively at a different hospital for three days and was then referred to our level I trauma center in view of increasing abdominal pain and distention. On admission in the Emergency Department (ED), her pulse rate was 120 per minute and blood pressure was 108/68 mm Hg. Clinical examination showed a distended abdomen with left hypochondrial pain. Ultrasonogram (USG) and Computed Tomography (CT) of the abdomen showed splenomegaly and grade III splenic injury with significant hemoperitoneum. Her hemoglobin was 2.9 g/dl with packed cell volume (PCV) of 12%. In view of low hemoglobin and possibility of pathologic spleen, splenectomy was done. Microscopic examination of the spleen showed hemangiolymphangioma. The patient was discharged on the 5(th) post-operative day and is doing well at 6 months of follow-up. PMID- 25114435 TI - The therapeutic challenges of degloving soft-tissue injuries. AB - BACKGROUND: Degloving soft-tissue injuries are serious and debilitating conditions. Deciding on the most appropriate treatment is often difficult. However, their impact on patients' outcomes is frequently underestimated. OBJECTIVES: We aimed to study the incidence, clinical presentation, management and outcome of degloving soft-tissue injuries. MATERIALS AND METHODS: We conducted a narrative traditional review using the key words; degloving injury and soft-tissue injuries through search engines PubMed, Science Direct, and Scopus. RESULTS: There are several therapeutic options for treating degloving soft-tissue injuries; however, no evidence-based guidelines have been published on how to manage degloving soft-tissue injuries, although numerous articles outline the management of such injuries. CONCLUSION: Degloving soft-tissue injuries are underreported and potentially devastating. They require early recognition, and early management. A multidisciplinary approach is usually needed to ensure the effective rehabilitation of these patients. PMID- 25114437 TI - Bedside ultrasound diagnosis of intracardiac paperclip. AB - Penetrating cardiac injuries are rarely reported in the literature. Foreign bodies are rarely seen in the heart and most patients with penetrating cardiac injuries die from hemorragic or pericardial tamponade before arriving at the hospital. Bedside ultrasonography is a highly valuable and readily learned tool that has expanded rapidly since its introduction more than 20 years ago. Our case was a 23-year-old convict brought to the emergency department (ED) with a history of continuous chest pain in the upper area of the left side of the chest for one week. Focused Cardiac Sonography (FOCUS) which was performed by emergency physician showed a strong echogenic linear structure with comet tail artifact, free floating in the mid-segment of the left ventricule. Exact localizations of the paperclips within the chest was obtained with multidetector computed tomography and one of them was seen in the left ventricular cavity. FOCUS plays a crucial role in these patients by diagnosing the injury and detecting the complications in emergency department. PMID- 25114438 TI - A patient fatality following the ingestion of a small amount of chlorfenapyr. AB - Chlorfenapyr has been used worldwide for agricultural pest control since 1995. Despite its widespread use, acute human poisoning data are insufficient; only a small number of fatalities from chlorfenapyr poisoning have been reported. The signs and symptoms of chlorfenapyr toxicity include nausea, vomiting, fever, rhabdomyolysis, among others. In addition, central nervous system effects in association with delayed toxicity have also been observed. Here, we detail a fatality resulting from delayed chlorfenapyr toxicity following the ingestion of a small amount of pesticide. PMID- 25114439 TI - Recurrent posterior reversible encephalopathy syndrome of the brainstem in a hypertensive patient with end-stage renal disease. AB - A 59-year-old man with end-stage renal disease was brought to our emergency department with complaints of headache, nausea, dysarthria, tic, and weakness involving the bilateral arms and legs. He had the similar episode 4 month before, when he was treated elsewhere. The patient had received hemodialysis three times per week. His medications included for hypertension. On examination at his arrival, he was alert with reduced concentration and incoherent thoughts. The blood pressure was 181/87 mmHg and other vital signs were normal. Neurological findings showed slight dysarthria and slow movements but no other abnormalities. Laboratory data showed increased serum creatinine and potassium presumably for a session of periodical hemodialysis but normal sodium concentration. His cerebrospinal fluid examination was normal. We treated him by hemodialysis. Diagnosis of PRES was most likely because of the clinical features and the MRI findings. His symptoms had disappeared immediately and completely after we controlled high blood pressure. MRI on 13 days after admission showed the improvement of the abnormal findings. Although the pathophysiology of PRES is incompletely understood, renal failure was known as one of the risk factors. A relative lack of sympathetic innervation of posterior circulation could not protect the area when severe hypertension makes auto-regulatory control collapsed. However, PRES of the brainstem is uncommon although the posterior circulation involves it. Because control of his hypertension was not appropriate in the outpatient settings before this event, it could have contributed to the recurrence in this patient. PMID- 25114440 TI - Acute aortic dissection is independent of weather conditions but statistically correlates with day of the week. PMID- 25114441 TI - Emergency hepatic artery embolization in a patient with post-traumatic ruptured hepatic artery pseudoaneurysm. PMID- 25114442 TI - A case of transient left bundle branch block after a cervical wound. PMID- 25114443 TI - Hair today, gone tomorrow. PMID- 25114444 TI - A review of psychiatric disorders comorbidities in patients with alopecia areata. AB - This is a review of psychiatric problems in patients with alopecia areata (AA). The electronic database of MedLine/PubMed was searched using the determined keywords. The rate of depression in children and adolescents with AA is up to 50%. Stressful life events are associated with AA. A rate of 39% for generalized anxiety disorders was reported. AA is highly associated with obsessive compulsive disorder (35.7%) in children and adolescents. Schizophrenia tended to be less seen in AA patients. PMID- 25114445 TI - Association between androgenetic alopecia and coronary artery disease in young male patients. AB - BACKGROUND: Several studies have demonstrated an association between androgenetic alopecia (AGA) and cardiovascular disease. Still controversies exist regarding the association. Are they truly associated? OBJECTIVE: The purpose of the present study was to assess the prevalence of AGA and establish its association in young (<45 years) Asian Indian Gujarati male patients having coronary artery disease (CAD). MATERIALS AND METHODS: Case-control prospective multicentric study was carried out on 424 men. Case group consisted of 212 male subjects having CAD (Group 1) and another 212, either sibling or first degree male relative of the case subjects (having no evidence of CAD) were considered as the control group (Group 2). Age, total cholesterol, incidence of diabetes mellitus, and hypertension were similar in both groups. The degree of alopecia was assessed using the Norwood-Hamilton scale for men. Statistical analysis was performed using Chi-square test. RESULTS: AGA was found in 80 (37.73%) young CAD patients (Group 1), whereas 44 (20.7%) of patients had alopecia in the control group (Group 2). There was statistically significant association between male AGA and CAD (P = 0.001). Odds ratio was 2.70 (95% confidence interval [CI], 1.72 +/- 4.26). Statistically significant association was found between high grade baldness (Grades IV-VII) and CAD in young men (P < 0.05). Odds ratio = 2.36 (95% CI, 1.108 +/- 5.033). There is statistically significant association of AGA in young Asian Gujarati male with CAD and the prevalence of AGA in young CAD patient is 37.73%. CONCLUSION: This study implies early onset AGA in male is independently associated with CAD, though mechanisms need to be investigated. PMID- 25114446 TI - Quality of life in alopecia areata: a case-control study. AB - BACKGROUND: Although alopecia areata (AA) is typically seen by medical staff as a benign, not life-threatening cosmetic disease, some studies have found significant impairment in quality of life (QL) in AA patients. There are no studies that assess QL in Brazilian AA patients. OBJECTIVES: To evaluate QL in AA patients, using the 36-item Short-Form Health Survey (SF-36). The most affected SF-36 dimensions were compared to two culturally different AA QL studies. MATERIALS AND METHODS: We performed a case-control study with 37 AA patients and 49 age- and sex-matched volunteer blood donors. The results of a Turkish and a French study were compared to our results. RESULTS: The dimensions social functioning (P = 0,001), role emotional (P = 0,019), and mental health (P = 0,000) scored statistically lower in the AA group in relation to controls, suggesting a worse QL. Incomparison to the Turkish and French studies, we found: (1) On the dimension role emotional, QL was equally impaired; (2) on the dimension social functioning, it was not different than the Turkish study; (3) social life of French AA patients was more affected; and (4) vitality and mental health dimensions were significantly more affected in French and Turkish patients. CONCLUSIONS: Impairment in QL in AA patients affected psychological, emotional, and social aspects of theirlives. Despite the scores of SF-36 dimensions varied significantly among different cultural groups, impairment of QL was found in all three studies; thus, we can suppose that these findings are not linked to a specific culture. PMID- 25114447 TI - 'Ho-ver'ing Over Alopecia Areata: Histopathological Study of 50 Cases. AB - BACKGROUND: Different studies have been done on this topic, most of the older studies on the vertical section confirm that peribulbar infiltrate is an important finding, however the newer studies on the horizontal section, mention decreased anagen to telogen ratio, decreased terminal to vellus hair ratio and a decreased follicular count. These studies on horizontal (transverse sections) have shown that transverse sectioning is superior and more diagnostic in studying alopecias. However, these studies are based on multiple cut sections, because in a single cut section, we may miss a few hair bulbs above or below, depending on where the section is taken. Hence this makes it a time consuming, technically challenging and expensive procedure. OBJECTIVES: 1. To compare the histopathological features of single vertical section versus a single horizontal section cut in the reticular dermis. 2. To determine if a single horizontal section is sufficient to report a biopsy of alopecia areata compared to multiple sections. MATERIALS AND METHODS: To compare the findings, in 50 patients with localized alopecia areata, 25 sectioned horizontally and 25 vertically, single section. Only three of the common findings, peribulbar infiltrate, intrabulbar infiltrate and perifollicular microscarring was considered and reported. RESULTS: Once the anagen to telogen ratio is excluded from the comparison, diagnosis made on the basis of a single horizontal section is considered sufficient to give us an aid toward the prognosis. PMID- 25114448 TI - Trichofolliculoma presenting as lobulated mass: a rare presentation. AB - Trichofolliculoma represents abortive differentiation of pluripotent skin cells toward hair follicles. We present a case of an adult female with lobulated mass involving the tip and dorsum of the nose for the last 15 years. The systemic and radiological examinations were noncontributory. The clinical diagnosis was thought to be dermoid cyst. The fine-needle aspiration cytology of the lobulated mass was performed, and the cytology smears showed anucleate squames admixed with sebaceous cells. The possibility of a benign skin adnexal lesion was suggested. The biopsy was done, and the final diagnosis of trichofolliculoma was made. The wide local excision of the mass was performed, and no recurrence was noted during the follow-up of 1 year. PMID- 25114449 TI - Three different dermoscopic view of three new cases with pilomatrixoma. AB - Pilomatrixoma is a benign soft tissue neoplasm originated from follicular matrix of hair and is also known as Malherbe's calcified epithelioma. Some lesions are located on the skin and are usually misdiagnosed. A small number of patients had been dermoscopically examined. In this article, three patients of pilomatrixoma who had three different dermoscopic views were evaluated and discussed in concordance with the literature. PMID- 25114450 TI - Trichomegaly of eyelashes after treatment with erlotinib in carcinoma pancreas. AB - Epidermal growth factor receptor (EGFR) inhibitors have been widely used for the treatment of epithelial malignancies. A wide spectrum of skin toxicities have been described in patients receiving EGFR inhibitors. Trichomegaly, especially of the eyelashes is a rare side effect of this therapy. We report a case of trichomegaly of eyelashes in a 39-year-old male, a case of carcinoma pancreas. This side-effect of these medications gives prospects as a therapy to stimulate the growth of hair. PMID- 25114451 TI - The action of prostaglandins on ciliary hypertrichosis: a case report of pachydermoperiostosis. AB - Pachydermoperiostosis or primary hypertropic osteoarthropathy is a rare hereditary disorder that was first described in 1868. It is characterized by digital clubbing, pachydermia (thickening of the facial skin and/or scalp), and periostosis (swelling of periarticular tissue and subperiosteal new bone formation). We report a case of a patient with the complete form of the disease, and with a unique appearance of the hair shaft and eyelashes. The authors propose a possible mechanism to justify the abnormalities observed in the patient's hair shafts regarding the metabolism of prostaglandins and its relationship with the hair follicle physiological cycle. PMID- 25114453 TI - Trichonodosis. AB - Trichonodosis is characterized by knotted hair on the distal portion of the hair shaft. This may be spontaneous or secondary to mechanical factors like vigorous scratching or combing the hair. We report a case of spontaneous trichonodosis with abnormal scalp and body hair. PMID- 25114454 TI - Diode Laser: Permanent hair "Reduction" Not "Removal". PMID- 25114452 TI - Primary idiopathic pseudopelade of brocq: five case reports. AB - Pseudopelade of Brocq (PPB) is a rare, idiopathic self-limiting hair disorder resulting in progressive cicatricial alopecia primarily involving the parietal scalp and vertex. The general pathogenesis of scarring alopecias has been focused on theories of stem cell failure and sebaceous gland destruction. Acquired immunity, Borrelia infection and senescence of follicular stem cell reservoir plays suspected role. It classically presents as porcelain white hypopigmented and slightly depressed atrophic plaque. There is no standard treatment for PPB. Here, we present five cases which were labeled as primary idiopathic PPB, as on histopathology no specific changes of any cicatricial alopecia were seen. PMID- 25114455 TI - Is there sufficient research data to use platelet-rich plasma in dermatology? PMID- 25114456 TI - Trichotillomania associated with bipolar disorder and obsessive compulsive disorder: pathoplasty or comorbidity? PMID- 25114457 TI - Editorial. PMID- 25114458 TI - Oral Cavity Cancers -Level v Metastasis. PMID- 25114459 TI - Ultrasonic shears versus electrocautery in axillary dissection for breast cancer a randomized controlled trial. AB - Theoretical advantages of use of Ultrasonic shears include less tissue damage and better sealing of lymphatic vessels. This may play a role in reducing prolonged drainage following axillary dissection for breast cancer. We conducted a prospective randomized controlled study to evaluate efficacy of ultrasonic shears over cautery for axillary dissection. Between April 2011 and April 2013, 92 patients were randomized to undergo axillary dissection with either ultrasonic shears (n = 46) or electrocautery (n = 46). Primary endpoints were time till drain removal and cumulative axillary drainage. Categorical data were compared by Pearson's chi-squared test. Continuous variables were compared by Independent t test or Mann Whitney U test. Data was analyzed using SPSS version 18.0. Both groups were comparable with respect to clinical and pathologic characteristics. Clinical characteristics of mean age, body mass index, side of tumor, neoadjuvant chemotherapy, and type of surgery (breast conservation or mastectomy) were similar. Pathologic variables (weight of specimen, number of lymph nodes harvested, pathologic T and N status, as well as grade of tumor) were also comparable among the two groups. There was no statistically significant difference in either primary endpoint of time till drain removal (15 vs. 14.5 days, p = 0.73) or cumulative axillary drainage (1,260 vs. 1,086.5 ml, p = 0.79). Patient and disease characteristics among the two groups were similar. But, there was no difference in either primary endpoint of cumulative axillary drainage or time to drain removal. We conclude that there is no advantage to use of ultrasonic shears over cautery in reducing drainage following axillary dissection for breast cancer. PMID- 25114460 TI - Role of frozen section in intraoperative assessment of ovarian masses: a tertiary oncology center experience. AB - Surgical management of ovarian lesions vary considerably depending on the nature of the lesion. As the preoperative imaging and serum tumor marker levels are of limited value in the proper categorization of ovarian lesions, intraoperative pathological assessment is commonly requested for a primary diagnosis. Aim of the study is to assess the accuracy of the frozen section in the diagnosis of ovarian masses in our center and to analyze the causes of diagnostic discrepancies. In this retrospective study, frozen section diagnosis of 233 cases of ovarian masses was compared with the permanent section diagnosis. The overall accuracy of frozen section was 91.85 %. The sensitivity of frozen section diagnosis for benign, borderline and malignant tumors was 99.2, 88.46 and 82.95 % respectively. The corresponding specificity was 96.5, 93.23 and 99.3 %. There were 19 discordant cases including 18 false negative cases and one false positive case. Frozen section is an important diagnostic tool to determine the nature of ovarian masses. Careful macroscopic examination, evaluation of multiple sections along with clinical and radiological findings helps to reduce false positive and false negative results. Frozen section examination has limitations especially in cases of borderline tumors. This modality is most effective when the pathologist and surgeon are aware of the advantages and limitations. PMID- 25114461 TI - Cervical node metastasis in T1 squamous cell carcinoma of oral tongue- pattern and the predictive factors. AB - BACKGROUND: The squamous cell carcinoma (SCC) of the oral tongue is a common cancer in India. Elective lymphadenectomy is generally performed in all patients with T2-T4 tumors. In this study we have tried to analyze the pattern and risk factors associated with lymph node metastasis in T1 tongue cancers. METHODS: A retrospective review of the records of 57 patients undergoing surgery for treatment of T1 sqamous cell carcinoma of oral tongue was carried out. The clinicopatological features of the tumor, pattern of nodal metastasis and the risk factors associated with lymph node metastasis were studied. RESULTS: Totally 57 patients with T1 tumor underwent excision of the primary and modified neck dissection (MND). Lymph node metastasis was found in 36.8 % of the patients. Level I to Level II was the commonest site of metastasis. Skip metastasis at level III and IV was found in 8.5 % of the patients and isolated skip metastasis at level IV in 1.5 % of the patients. The risk factors associated with the lymph node metastasis on univariete analysis were; higher grade, tumor size >1 cm and tumor thickness >3 mm. On multivariate analysis only the tumor thickness was found to be a risk factor for the lymph node metastasis (hazard ratio of 21.59). CONCLUSIONS: T1 sqamous cell carcinoma of tongue is associated with a high incidence of lymph node metastasis. Elective neck dissection should be considered in all patients with tumors more than 3 mm in thickness. PMID- 25114463 TI - Clinical Outcomes in the Google Era: The PB Desai Oration, ASICON 2013. AB - This article is based upon the PB Desai Oration which was given by the author in Ahmedabad on 28th December 2013 at the National Congress of the Association of Surgeons of India at the invitation of the Executive Board of the Indian Association for Surgical Oncology. PMID- 25114462 TI - The risk and pattern of pelvic and para aortic lymph nodal metastasis in patients with intermediate and high risk endometrial cancer. AB - There is a continuous debate about the extent and prognostic value of retroperitoneal lymphadenectomy in endometrial cancer. Systematic pelvic and para aortic lymphadenectomy in endometrial cancer provides a more accurate assessment of neoplastic spread and may help in better individualization of patients for adjuvant therapy. To evaluate the risk and pattern of retroperitoneal lymph nodes metastasis in patients with endometrial cancers having intermediate and high risk factors for nodal metastasis and recurrence. We conducted a prospective nonrandomized study of 62 cases of high risk endometrial cancers examined and treated at our regional cancer institute between the years 2008 and 2012. The inclusion criteria: The intermediate risk; all patients having grade 3 or undifferentiated adenocarcinomas with less than half MI and the grade 1, 2 tumors having more than half MI with tumor size >2 cm. The high risk group; all the patients having grade 3 or undifferentiated adenocarcinomas with more than half MI, the grade 1, 2 tumors with lymph vascular space invasion (LVSI) or cervical stromal invasion as depicted by pre-operative MRI. The type 2 histology uterine papillary serous, clear cell and squamous cell carcinomas. The patients staging was carried out according to the classification established by the FIGO for endometrial cancer in 2009. The Chi-square test was used to analyze the correlation between tumor grade, myometrial invasion, size of the lesion and lymph nodes metastasis and Fisher's correction done whenever the frequency distribution was less than five. The patients mean age was 58.3 (range 31 to 76 years). A total of 118 endometrial cancer patients were treated during the study period. The 56 (47.5 %) patients belonged to low risk and 62 (52.5 %) patients belonged to high risk endometrial cancers. The 52 of 62 cases were eligible for the analysis. The 10 patients' were excluded from further analysis as the post operative specimens final histopathologic examinations in nine cases revealed carcinosarcoma uterus and one case with yolk sac tumor of endometrium. The total 17(32.7 %) of 52 cases had retroperitoneal nodes metastasis; nine of 17 (52.9 %) in this group had both pelvic and para-aortic lymph nodal metastasis and one of 17 (5.9 %) had isolated para-aortic lymph nodal metastasis. The high grade tumors (grade 3) revealed 41.4 % pelvic and 20.7 % para-aortic lymph nodes metastasis and there was statistically significant higher nodal metastasis in both pelvic and para-aortic lymph nodes with increasing depth of myometrial invasion (P = 0.0119 and P = 0.0001) and increasing size of the lesion. (P = 0.04 and P = 0.0501). The intermediate and high risk endometrial cancer is associated with greater degree of lymph node metastasis. A complete surgical staging which involves extrafascial hysterectomy or a type 3 radical hysterectomy when there is a cervical involvement, along with bilateral salphingo-oophorectomy, pelvic, para aortic lymphadenectomy and an omentectomy when indicated as in the present study, is a valuable modality of treatment in intermediate and high risk cases of endometrial cancers for determining the prognosis and appropriate categorization of these women for adjuvant therapy. It is also possible to achieve a complete surgical staging in these groups of women with acceptable morbidity when performed by a trained gynaecologic oncologist. PMID- 25114464 TI - Xeroderma pigmentosum: clinicopathological review of the multiple oculocutaneous malignancies and complications. AB - Multiple oculo-cutaneous malignancies are a common manifestation on sun-exposed facial areas in patients with Xeroderma pigmentosum (XP). Commonly seen are the basal cell carcinoma and the squamous cell carcinomas which manifest in the early first decade in contrast to fifth and sixth decade in the general population. XP manifests as photosensitivity, hyperpigmentation, premature skin aging and malignant changes like squamous cell carcinoma, basal cell carcinoma, fibrosarcoma and rarely malignant melanoma as well as internal malignancies. We report 11 cases of Xeroderma pigmentosa managed in our institute which included sex males and five females. All had photosensitivity, hyperpigmentation and consanguinity with facial malignant lesions like SCC and BCC. Ocular signs of photophobia and excessive lacrimation was seen in all the cases while blurring of vision due to corneal clouding, corneal injection, pterygium and limbal SCC were seen in 5 cases. SCC of the lids were seen in 7 cases while BCC seen in 8 cases and limbal and conjunctival SCC seen in one case. All were managed with excision while one case of melanoma with neck secondaries needed radical neck dissection while the other orbital exenteration. Oculo-cutaneous malignancies occur in the sun exposed areas so patients are advised regular follow up with speciality care. Awareness about the rare condition and importance of early detection and prevention of UV rays induced skin damage should be propagated. The disease is ultimately fatal, life can be prolonged by simple preventive measures to minimize sun exposure and early detection of the skin lesions and management. PMID- 25114465 TI - Virtual reality surgical simulators- a prerequisite for robotic surgery. AB - The field of computer assisted minimally invasive surgery is rapidly expanding worldwide, including in India. With more hospitals in India contemplating the acquisition of a robotic platform, training of robotic surgeons is becoming essential. Virtual reality simulators can be used for surgeons to become acquainted with the robotic console prior to live surgery. Our aim was to evaluate the amount of simulator training required before a surgeon first operates on the da Vinci(r) Surgical System. Simulations were conducted on the Intuitive Surgical's da Vinci(r) Robot Skill Simulator using the software obtained from Mimic Technologies. Participants included attending staff surgeons experienced in robotic surgery and novices. A set of seven activities were chosen for each participant. Based on the mean exercise score from the first attempt, staff surgeons outperformed the novices in all exercises. However, the difference in score between the staff and the novices decreased after the participants repeated the exercises and by the sixth attempt most of the novices obtained similar scores to the staff, suggesting that this might be at present the minimum set of repetitions indicated (or required) prior to performing life robotic surgery. PMID- 25114466 TI - Chondroradionecrosis of larynx a delayed complication of radiotherapy: management and review of literature. AB - Background/objectives Chondroradionecrosis (CRN) of the larynx is a rare and grave complication of radiotherapy which can be fatal if not managed aggressively. A recent trend towards organ preservation protocols towards even advanced stage laryngeal malignancies and with further advances in terms of technology and safety radiation as external beam and intensity modulated varieties are preferred for certain stages of squamous cell carcinomas. Materials and methods We are reporting a series of 4 cases of CRN of the larynx treated in our hospital with 3 cases of stage III carcinoma glottis and one stage III carcinoma supraglottis with no nodal metastasis. One glottis cancer had 2 sittings of laser microlaryngeal excision earlier. All were in grade 4 CRN and one improved with medical line and HBO and the other 3 progressed and salvage laryngectomy and pectoralis major myocutaneous flap to cover the fistulous skin defect was grafted. CONCLUSION: Laryngeal CRN being a rare and intensely morbid complication of radiotherapy should be suspected and diagnosed at the earliest by endoscopic and imaging methods. Disease progression and chances of tumor recurrence should be followed up with PET CT and a call on salvage laryngectomy with repair of the anterior neck defects with non irradiated musculocutaneous flaps or vascularised tissue transfer should be promptly taken. PMID- 25114468 TI - Intussusception of a small bowel large B-cell lymphoma. AB - Gastrointestinal tumors can rarely cause intestinal intussusception. Herein, we describe a 74 year-old male with a presumed diagnosis of Crohn's disease who presented with persistent symptoms refractory to medical management. Radiography demonstrated small bowel intussusception into the cecum. Lower endoscopy with biopsy diagnosed small bowel large Bcell lymphoma. Management included laparoscopic ileocecectomy and adjuvant R-CHOP chemotherapy. Long term outcomes of small bowel large B-cell lymphoma are related to disease stage at diagnosis, and average close to 75 %. PMID- 25114469 TI - p53: Revealing the Unusual Suspect: a Study and Field Cancerization Minireview. PMID- 25114467 TI - Chemotherapy and targeted therapy for gall bladder cancer. AB - Gall bladder cancer is a common cancer in the Ganges belt of North-eastern India. In view of incidental diagnosis of gall bladder cancer by physicians and surgeons, the treatment is not optimised. Most patients present in advanced stages and surgery remains the only option to cure. This review highlights the current evidence in advances in systemic therapy of gall bladder cancer. PMID- 25114470 TI - The aesthetic and oncological challenges in the management of an atypical nodular hidradenoma of the pinna. AB - Nodular hidradenomas are benign adenomatous tumours of sweat gland origin, which commonly arise from the skin of the head, neck and extremities. Some of these benign appearing lesions exhibit aggressive clinical behaviour with rapid growth, pigmentation and ulceration. These tumors are designated as "atypical nodular hidradenomas" and are known to histologically possess some focal atypical features i.e. nuclear pleomorphism, focal necrosis or prominent mitotic activity. Nodular hidradenomas involving the pinna are rare and to the best of our knowledge there have been no prior reports in the English language literature. We describe a unique case of a 45-year-old woman with an atypical nodular hidradenoma of the left pinna and discuss the aesthetic and the oncological issues pertaining to the reconstruction of the pinna. PMID- 25114471 TI - Pleomorphic adenoma of breast-a case report and review of literature. AB - Pleomorphic adenoma (PA) is a rare benign tumour of the breast. However inadequate surgery of this tumour, which is notorious for its pseudopod like extension into adjacent tissue, results in recurrence. We report a case of pleomorphic adenoma of the breast that has been excised at a local hospital and then referred to a tertiary care hospital for definite management. The diagnostic dilemmas and optimal management, of such cases where dependable pathology report and details of primary surgery are often not available, are discussed. PMID- 25114472 TI - Primary angiosarcoma of breast: a case report. AB - Primary breast sarcomas are rare entities. These malignant tumors originate from mesenchymal glandular breast tissue and account for <1 % of all breast cancer cases. Angiosarcomas are rare malignant tumors that arise from endothelial cells lining vascular channels. Most angiosarcomas are secondary to radiotherapy treatments for breast cancer or to an arm lymphoedema subsequent to a modified radical mastectomy. Primary angiosarcomas are rare and account for 0.04 % of all malignant breast tumors. PMID- 25114473 TI - Aneurysmal bone cyst of medial end of clavicle in a child, a rare case report. AB - Aneurysmal bone cyst is a locally aggressive benign tumor accounting for 3 % of all benign bone tumors. It most commonly arises from ends of long bones and relatively rare in flat bones. Clavicle is a very rare site for bone tumors with secondaries more common than primaries. Very few cases of aneurysmal bone cyst have been reported in literature. We hereby report interesting and a rare case of aneurysmal bone cyst of medial end of clavicle in a eight year old lady which was treated with extended curettage and calcium sulfate bone grafting. PMID- 25114474 TI - Steatohepatitic hepatocellular carcinoma-a case report with literature review. AB - We report a case of a 65 year old male who presented with complaints of pain right upper abdomen for past 3 months. He was a known diabetic and hypertensive. On evaluation he was found to have space occupying lesion in the right lobe of the liver. USG Guided FNC done showed a Hepatocellular Carcinoma with predominant steatosis. He underwent Right Hepetectomy for the same and Histopathological examination revealed a Steatohepatitic Hepatocellular Carcinoma with background liver showing minimal steatosis and no significant fibrosis. This case is reported to provide better insight into the understanding of pathophysiology of metabolic syndrome as an etiological agent for development of HCC. PMID- 25114475 TI - Right hepatectomy in icteric type hepatocellular carcinoma-report of a case and literature review. PMID- 25114476 TI - Recent research about mild cognitive impairment in China. AB - The rapid aging of the Chinese population has spurred interest in research about the cause and prevention of dementia and its precursor, mild cognitive impairment (MCI). This review summarizes the last decade of research in China about MCI. Extensive research about the epidemiology, neuropsychological characteristics, diagnosis, genetic etiology, neuroimaging and electrophysiological changes, and treatment of MCI has provided some new insights but few breakthroughs. Further advances in the prevention and treatment of MCI will require a greater emphasis on multi-disciplinary prospective studies with large, representative samples that use standardized methods to assess and monitor changes in cognitive functioning over time. PMID- 25114477 TI - Randomized controlled trial of four protocols of repetitive transcranial magnetic stimulation for treating the negative symptoms of schizophrenia. AB - BACKGROUND: The negative symptoms of schizophrenia are not effectively treated with antipsychotic medications. Repetitive transcranial magnetic stimulation (rTMS) is an alternative approach that may be more effective in treating negative symptoms, but there has been little research comparing the effectiveness of different rTMS stimulation protocols. OBJECTIVE: Compare the effect of four different rTMS protocols in the treatment of the negative symptoms of schizophrenia. METHODS: Ninety-six patients with schizophrenia who had prominent negative symptoms were randomly assigned to four treatment groups: 10 Hz, 20 Hz, theta burst stimulation (TBS), and mock rTMS (i.e., the control group). In the first three groups, the left dorsolateral prefrontal cortex was stimulated at 80% of the motor threshold five times per week for four weeks. Before and after the treatment, evaluators who were blind to the group assignment of patients administered the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS) and the Treatment Emergent Symptom Scale (TESS). RESULTS: Three of the 96 patients dropped out during the trial (two from the control group and one from the 20 Hz group). Compared to the control group, after 4 weeks of rTMS treatment all three treatment groups had lower scores on the PANSS negative symptom subscale, the PANSS general psychopathology subscale, and the SANS. The TBS group had significantly larger reductions in these scores than the 10 Hz group and the 20 Hz group, but there were no significant differences between the 10 Hz and 20 Hz groups. There were no pre- versus post treatment differences in the PANSS positive symptom subscale scores between the four groups. No serious adverse events occurred and there were no statistically significant differences in the TESS scores across the four groups. CONCLUSIONS: We find that rTMS, particularly the TBS stimulation protocol for rTMS, is a safe and effective treatment method for patients with schizophrenia who have prominent negative symptoms. Longitudinal studies with large samples are needed to optimize the rTMS treatment, to identify the stimulation protocol, duration, intensity and treatment interval that provides the best therapeutic result at the lowest risk to the patient. PMID- 25114478 TI - Cross-sectional survey of the relationship of symptomatology, disability and family burden among patients with schizophrenia in Sichuan, China. AB - BACKGROUND: Schizophrenia is a chronic condition that leads to high rates of disability and high levels of family burden but the interactive relationship between these variables remains unclear, particularly in low- and middle-income countries where the vast majority of patients live with their families. AIM: Assess the symptom severity, level of disability, and family burden among clinically stable outpatients with schizophrenia in Sichuan, China. METHODS: A total of 101 clinically stable outpatients with schizophrenia who had a median duration of illness of five years were assessed using the World Health Organization Disability Assessment Scale 2.0 (WHODAS II), the Positive and Negative Syndrome Scale (PANSS) and the Family Adaptation, Partnership, Growth, Affection and Resolve Index scale (APGAR); and their caregivers were surveyed using the Family Burden Interview Schedule (FBIS). RESULTS: Among the 101 patients, 92 lived with their immediate family members, 74 had clinically significant disability, and 73 were unemployed. The level of disability was associated with the severity of symptoms (r=0.50, p<0.001), duration of illnesses (r=0.22, p=0.028), age of onset (r=-0.22, p=0.024) and patients' level of satisfaction with family support (r=-0.30, p=0.020). Disability was also associated with the overall level of family burden (r=0.40, p<0.001), and with several subtypes of family burden: financial burden (r=0.21, p=0.040), the degree of disruption in family routines (r=0.33, p=0.001), the effect on family leisure activities (r=0.31, p=0.001) and the quality of family interactions (r=0.43, p< 0.001). Four variables remained significantly associated with the level of disability in the stepwise multivariate linear regression: duration of illness, severity of symptoms, patient satisfaction with family support, and the overall burden of the illness on the family. CONCLUSIONS: Even after adjusting for the severity of patients' symptoms, patient disability is independently associated with family burden. This highlights the importance of targeting both symptoms and disability in treatment strategies for this severe, often lifelong, condition. In countries like China where most individuals with schizophrenia live with their families, family burden is an important component of the impact of the illness on the community that should be included in measures of the relative social and economic importance of the condition. PMID- 25114479 TI - Five-year follow-up study of multi-domain cognitive training for healthy elderly community members. AB - BACKGROUND: Cognitive training, a safe non-pharmacological intervention, may help mitigate cognitive decline and prevent the development of dementia in elderly individuals. OBJECTIVE: Evaluate the long-term effects of cognitive training among healthy elderly community members. METHODS: Healthy individuals 70 years of age or older from one urban community in Shanghai were screened and the 151 individuals who met inclusion criteria were assigned either to an intervention group (n=90) or a control group (n=61). The intervention involved twice-weekly training in reasoning, memory, and strategy that continued for 12 weeks (a total of 24 sessions). Participants were assessed at baseline and at 12 weeks, and 5 years after enrollment using the Chinese versions of the Neuropsychological Test Battery for Elderly persons (NTBE), the Stroop Color-Word Test, and a general health questionnaire. RESULTS: Forty-nine (54%) intervention group subjects and 33 (54%) control group subjects completed the 5-year follow-up. There were few differences in the baseline neurocognitive measures of those who did and did not complete the 5-year follow-up, and there were few differences between those who dropped out of the intervention group compared to those who dropped out of the control group. At the 5-year follow-up, individuals in the intervention group performed better than those in the control group on only 5 measures (in the Trails Making A Test and the Cancellation Test 3) of the 61 measures assessed by NTBE and the Stroop tests, but none of these differences met the pre-determined required level of statistical significance (p=0.0008). CONCLUSION: We do not confirm the results of previous studies that report long-term benefits of brief cognitive training courses for elderly community residents. Our failure to identify differences in cognitive functioning five years after cognitive training is not likely due to differential dropout between the intervention and control groups but may be related to the relatively small sample and the large number of measures being assessed. Future intervention studies for cognitive training in the elderly should be hypothesis driven (i.e., focused on a single outcome measure of interest), use much larger samples, and include regular booster sessions as part of the cognitive training package. PMID- 25114481 TI - Challenges in the diagnosis and treatment of transsexualism in contemporary China. PMID- 25114480 TI - Duration of untreated psychosis and clinical outcomes of first-episode schizophrenia: a 4-year follow-up study. AB - BACKGROUND: The relationship between the duration of untreated psychosis and long term clinical outcomes remains uncertain. OBJECTIVE: Prospectively assess the relationship of the duration of untreated psychosis on clinical outcomes in a sample of individuals with first-onset schizophrenia treated at the Pudong Mental Health Center from January 2007 to December 2008. METHODS: Information about general health, psychotic symptoms and social functioning were collected using the Brief Psychiatric Rating Scale (BPRS), Treatment Emergent Symptom Scale (TESS), Morningside Rehabilitation Status Scale (MRSS), and Social Disability Screening Schedule (SDSS) at baseline and in June 2010 and June 2012. RESULTS: The 43 individuals with first-episode schizophrenia participating in the study were divided into short (<24 weeks) and long (>24weeks) duration of untreated psychosis (DUP) groups. The mean (sd) duration of follow-up was 1197 (401) days in the short DUP group and 1412 (306) days in the long DUP group (t=9.98, p=0.055). Despite less prominent psychotic symptoms at the time of first diagnosis among patients who had a long DUP compared to those with a short DUP (BPRS mean scores, 42.5 [8.4] v. 50.0 [10.6], t=2.42, p=0.0210) and a similar number of clinical relapses (based on positive symptoms assessed by the BPRS), patients with a long DUP were more likely to require hospitalization at the time of first diagnosis (52% [11/21] v. 9% [2/22], chi(2) =9.55, p=0.002) and more likely to require re-hospitalization during the first two years of treatment (67% [14/21] v. 32% [7/22], chi(2) =5.22, p=0.022). Moreover, after four years of routine treatment, despite a similar severity of positive symptoms, patients who had had a long DUP prior to initiating treatment had significantly poorer social functioning than those who had had a short DUP (SDSS mean scores, 7.0 [5.2] v. 3.4 [4.9], t=2.20, p=0.035). CONCLUSIONS: These findings show that despite having a similar level of psychotic symptoms - as measured by the BPRS - compared to patients with a short DUP, patients with schizophrenia who have a long DUP prior to initial treatment have poorer long-term social functioning. This confirms the clinical importance of the early recognition and treatment of individuals with chronic psychotic conditions. PMID- 25114482 TI - Case report of refractory tardive dystonia induced by olanzapine. AB - SUMMARY: Tardive dystonia (TDt), a cluster of extrapyramidal symptoms that are caused by long-term use of antipsychotic medication, is characterized by difficulty in autonomic movements of skeletal (voluntary) muscles and consequent deformations of the body. TDt is rarely seen among patients taking olanzapine, but olanzapine was the precipitating antipsychotic medication in this 22-year old male patient with schizophrenia who developed lip puckering, persistent involuntary torticollis, muscular pain, axial dystonia and unstable gait after taking a standard dose of olanzapine regularly for about one year. His symptoms did not resolve after his olanzapine was stopped. Four months of treatment with clozapine combined with magnesium valproate, vitamin E, tiapride, and lorazepam did not lead to any improvement in the dystonia. PMID- 25114484 TI - Report on the Shanghai Conference of the ICD-11 Field Studies Coordinating Group. PMID- 25114483 TI - Establishing a data monitoring committee for clinical trials. AB - SUMMARY: A data monitoring committee (DMC) is a group of clinicians and biostatisticians appointed by study sponsors who provide independent assessment of the safety, scientific validity and integrity of clinical trials. In the United States, the Food and Drug Administration requires the formation of DMC in all trials that assess new interventions. DMC are also strongly recommended in other clinical studies that have substantial safety issues, that have double blind treatment assignment or that are expected to have a major impact on clinical practice. They are important in clinical research in psychiatry because they provide an added layer of protection for the vulnerable populations that are often enrolled in such studies. This report describes the role, formation and operation of DMC. PMID- 25114485 TI - Neuroimaging studies of depressive disorders in China since 2000. AB - SUMMARY: This paper reviews neuroimaging studies of depressive disorders conducted in Chinese populations since 2000. Both cross-sectional and longitudinal studies using structural and functional imaging techniques have compared different types of depressed individuals, with and without specific genotypes, and the characteristics of depressed individuals before and after treatment with antidepressants. Many of the findings are unstable - probably because most of the studies are underpowered - but there have been some important contributions to the international literature. Future studies in China need to use standardized methods, longitudinal designs, and joint application of both structural and functional MRI. PMID- 25114487 TI - Changes in behavior and in brain glucose metabolism in rats after nine weeks on a high fat diet: a randomized controlled trial. AB - BACKGROUND: A high-fat diet (HFD) is a well-known risk factor for cardio cerebrovascular disease but the relationship between a HFD and depressive symptoms remains unknown. OBJECTIVE: Compare changes in behavioral and measures of brain glucose metabolism in rats fed a HFD to those of rats fed a standard diet. METHODS: Twenty male Sprague-Dawley rats were randomly assigned to a study group (n=10) that received a high fat diet for 9 weeks or a control group (n=10) that received a standard diet for 9 weeks. At baseline and at the end of the 9 week trial assessments included body weight, serum lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), the sucrose preference test, and the open field test. The rate of brain glucose metabolism in different brain regions (assessed using micro positron emission tomography) at the end of the trial was also compared between the two groups of rats. RESULTS: Nine weeks of a HFD in rats resulted in the expected increase in weight and changes in serum lipid levels, but it was also associated with a decreased preference for sucrose (which may be due to a loss of interest in pleasurable activities), increased weight-adjusted water intake, and a significant deactivation of the right thalamus and right striatum (based on decreased rates of glucose metabolism). In the HFD group the magnitude of the drop in the sucrose preference was strongly correlated to the magnitude of the deactivation of the right thalamus (r=0.78) and the right striatum (r=0.81). CONCLUSIONS: These findings support hypotheses about the role of a HFD in the causal pathway for depressive symptoms. Further work is needed to clarify the underling mechanism, but it appears that the interaction between the content of the diet and the limbic system-striatum-thalamus circuit plays a role in both eating behavior and depressive symptoms. PMID- 25114486 TI - Two-year prospective case-controlled study of a case management program for community-dwelling individuals with schizophrenia. AB - BACKGROUND: A community-based rehabilitation program is an essential element of the comprehensive treatment of individuals with schizophrenia. OBJECTIVE: Assess the long-term effects of a community-based case management program for providing rehabilitations services to individuals with schizophrenia. METHODS: A total of 730 community-residing participants who met ICD-10 diagnostic criteriafor schizophrenia were enrolled, 380 in the case management group and 350 in the control group from two districts in Shanghai. Case management involved monthly training visits with patients and their co-resident family members that focused on encouraging medication adherence. Participants were assessed every three months for 24 months with the Camberwell Assessment of Need (CAN), Positive and Negative Syndrome Scale (PANSS), WHO-Disability Assessment Scale (WHO-DAS), and the Quality of Life Scale (QOLS). Level of discomfort due to side-effects was also assessed every three months. Individuals who discontinued their antipsychotic medication without physician approval for one month or longer at any time during follow-up were classified as 'self-determined medication discontinuation'. RESULTS: Compared to the treatment as usual group (i.e., follow up management every 3 months), by the end of the two-year follow-up those who participated in the case management program had significantly lower rates of medication discontinuation, significantly less severe negative symptoms, lower relapse rates and lower rehospitalization rates. Other factors that had an independent effect on discontinuation of medication included educational level (those with more education had higher discontinuation rates), lack of family supervision of medication, higher dosages of medication, and greater medication related discomfort. CONCLUSIONS: Case management is a feasible and effective long term method for improving the rehabilitation outcomes of community residents with schizophrenia. Our results highlight the need to involve family members in the management of patients' medication, to use the minimum effective dosage of medication, and to aggressively manage all side-effects. PMID- 25114488 TI - Retrospective assessment of factors associated with readmission in a large psychiatric hospital in Guangzhou, China. AB - BACKGROUND: Most psychiatric inpatients in China are involuntarily admitted by their families, resulting in relatively long admissions and relatively low readmission rates. However, this pattern may change after implementation of China's new national mental health law (promulgated in 2013), which restricts involuntary psychiatric admissions to the small proportion of mentally ill individuals who are a danger to self or others. AIM: Assess the factors associated with readmission rates of psychiatric inpatients in Guangzhou, China. METHODS: A retrospective analysis of data from the Guangzhou Psychiatric Hospital, one of the largest psychiatric hospitals in China, used Cox regression models to evaluate the relationship between age, gender, diagnosis, marital status, employment status, relationship with the primary caregiver, type of medical insurance, length of stay of the index admission, and the number of previous admissions to estimate the risk of readmission over the year following discharge. Multivariate regression is used to assess factors associated with the total time of readmission during the year of follow-up. RESULTS: Among 3455 patients admitted from 1 January 2011 to 31 December 2012 who had a mean (sd) length of stay of 65.7 (66.3) days, 476 (13.8%) were readmitted one or more times within one year of discharge. After considering all potential predictors of readmission in a multivariate survival analysis, the number of previous hospitalizations prior to the index admission was the only statistically significant predictor of readmission. The only factor that was significantly related to the total time of readmission was the duration of the index admission. CONCLUSION: Shorter length of stay was not associated with increased readmission rates in patients admitted to a large public psychiatric hospital in southern China. This suggests that the expected decrease in the length of psychiatric inpatient admissions that is likely to occur when, based on China's new regulations, most patients are admitted voluntarily may not lead to increased rates of readmission. Prospective studies with a more comprehensive set of outcome measures (including patient functioning, medication adherence, and family burden) are needed to monitor the effect of the law on patients and on the distribution of mental health services. PMID- 25114489 TI - Retrospective assessment of the prevalence of cardiovascular risk factors among homeless individuals with schizophrenia in Shanghai. AB - BACKGROUND: Cardiovascular diseases are increasingly important in China, but the prevalence of risk factors for cardiovascular diseases in the indigent mentally ill are unknown. AIM: Assess the prevalence of four key risk factors for cardiovascular disease -- hypertension, hyperglycemia, hyperlipidemia and smoking - among homeless patients with schizophrenia and identify factors associated with the presence of these risk factors. METHODS: We reviewed medical charts of 181 homeless and 181 non-homeless patients with schizophrenia or schizophreniform disorder admitted to the Shanghai Jiading Mental Health Center between May 2007 and April 2013. Demographic characteristics and risk factors of cardiovascular events were compared between the two groups. Logistic regression models identified the factors that were associated with the presence of one or more of the four risk factors. RESULTS: The prevalence of hypertension and hyperlipidemia were 19 to 20% in both males and females in the two groups; these rates are similar to those reported in the general population. The prevalence of hyperglycemia ranged from 11 to 15% among males and females in the two groups. Smoking was highly prevalent in male patients (82% in homeless males and 78% in non-homeless males) but, like in China generally, much less prevalent in female patients (7% in homeless females and 5% in non-homeless females). The logistic regression analysis found that male gender, older age, and urban (vs. rural) residence were independently associated with the presence of one or more of the four cardiovascular risk factors. Homelessness was not associated with the presence of cardiovascular risk factors. CONCLUSION: This study is the first known report on cardiovascular risk factors among homeless mentally ill in China. The study did not assess several important factors (such as the type, dose and duration of use of antipsychotic medication) but it was, nevertheless, able to show that, unlike in high-income countries, homelessness is not related to elevated risk of cardiovascular disease in Chinese individuals with mental illnesses. Prospective studies with the growing number of homeless individuals in China will be needed to get a clearer picture of the best ways to provide them with the health care services they need. PMID- 25114491 TI - Opportunities and challenges for promoting psychotherapy in contemporary China. AB - China's first mental health law, which went into effect last year, envisages a world in which psychotherapy is an integral part of all levels of medical care. There are many obstacles to achieving this goal. The new law empowers psychiatrists to provide psychotherapy but few of them have the time or inclination to do so because of the lower incomes generated by non-biological treatments. Trained clinical psychologists are in very short supply partly because of the lack of supervised training opportunities and partly because the current medical system - and the new mental health law - does not empower them to diagnose or treat patients without the direct supervision of a physician. Achieving the laudable goals of the new law will require substantial changes in the regulations and, perhaps more importantly, in attitudes about the role and status of psychologists within the medical care delivery system. PMID- 25114492 TI - Case report of comorbid alcohol-induced psychotic disorder and Madelung's disease. AB - Madelung's disease, also known as benign symmetric lipomatosis (BSL), multiple symmetric lipomatosis (MSL), fatty neck syndrome or Launois-Bensaude syndrome, is a rare disease characterized by the presence of multiple, symmetric, loose adipose tissues distributed around the neck, occipitalis, shoulder, back or chest. The fat masses are non-encapsulated and therefore can move freely between adjacent areas. This disease is most commonly seen among middle-aged Caucasian men of Mediterranean origins; it is rarely reported in Asia. Among individuals with Madelung's syndrome, 60 to 90% have a history of chronic alcohol abuse. We report a case of a 51-year-old Chinese man with a history of alcohol use disorder who had fat masses in his neck which gradually enlarged over a period of three years. Based on the case history and the results of physical examination, neck CT and other routine tests, he was diagnosed with Madelung's syndrome. PMID- 25114494 TI - Item response theory for measurement validity. AB - Item response theory (IRT) is an important method of assessing the validity of measurement scales that is underutilized in the field of psychiatry. IRT describes the relationship between a latent trait (e.g., the construct that the scale proposes to assess), the properties of the items in the scale, and respondents' answers to the individual items. This paper introduces the basic premise, assumptions, and methods of IRT. To help explain these concepts we generate a hypothetical scale using three items from a modified, binary (yes/no) response version of the Center for Epidemiological Studies-Depression scale that was administered to 19,399 respondents. We first conducted a factor analysis to confirm the unidimensionality of the three items and then proceeded with Mplus software to construct the 2-Parameter Logic (2-PL) IRT model of the data, a method which allows for estimates of both item discrimination and item difficulty. The utility of this information both for clinical purposes and for scale construction purposes is discussed. PMID- 25114493 TI - Use of diplotypes - matched haplotype pairs from homologous chromosomes - in gene disease association studies. AB - Alleles, genotypes and haplotypes (combinations of alleles) have been widely used in gene-disease association studies. More recently, association studies using diplotypes (haplotype pairs on homologous chromosomes) have become increasingly common. This article reviews the rationale of the four types of association analyses and discusses the situations in which diplotype-based analyses are more powerful than the other types of association analyses. Haplotype-based association analyses are more powerful than allele-based association analyses, and diplotype-based association analyses are more powerful than genotype-based analyses. In circumstances where there are no interaction effects between markers and where the criteria for Hardy-Weinberg Equilibrium (HWE) are met, the larger sample size and smaller degrees of freedom of allele-based and haplotype-based association analyses make them more powerful than genotype-based and diplotype based association analyses, respectively. However, under certain circumstances diplotype-based analyses are more powerful than haplotype-based analysis. PMID- 25114495 TI - Customized epithelial debridement for thin ectatic corneas undergoing corneal cross-linking: epithelial island cross-linking technique. AB - Thin corneas with a minimum corneal thickness less than 400 MUm after epithelial removal represent a contraindication to standard epithelium-off cross-linking (CXL) treatment due to a significant endothelial cell density decrease and potentiality of permanent haze development. Preoperative swelling of the cornea with hypoosmolar riboflavin solutions broadens the spectrum of CXL indications to thin corneas. However the iatrogenic swelling effect might not be durable throughout the CXL procedure increasing the risk of postoperative complications. The transepithelial CXL technique proposed for thin corneas demonstrated poor clinical results and mid- to long-term keratoconus instability. The epithelial island CXL technique with customized pachymetry-guided epithelial debridement was evaluated by means of in vivo laser scanning confocal microscopy, corneal topography, and clinical examination in a 1-year follow-up, in order to assess if it may be considered an alternative surgical option for keratoconic patients with thin corneas undergoing corneal collagen CXL. According to our clinical and in vivo micro-morphological results the technique results safe, and efficacious in stabilizing progressive keratoconus and may be considered a valid option in the treatment of thin ectatic corneas alone or in combination with hypoosmolar or dextran-free riboflavin solutions. PMID- 25114496 TI - Grader agreement, and sensitivity and specificity of digital photography in a community optometry-based diabetic eye screening program. AB - BACKGROUND: Digital retinal photography with mydriasis is the preferred modality for diabetes eye screening. The purpose of this study was to evaluate agreement in grading levels between primary and secondary graders and to calculate their sensitivity and specificity for identifying sight-threatening disease in an optometry-based retinopathy screening program. METHODS: This was a retrospective study using data from 8,977 patients registered in the North Nottinghamshire retinal screening program. In all cases, the ophthalmology diagnosis was used as the arbitrator and considered to be the gold standard. Kappa statistics were used to evaluate the level of agreement between graders. RESULTS: Agreement between primary and secondary graders was 51.4% and 79.7% for detecting no retinopathy (R0) and background retinopathy (R1), respectively. For preproliferative (R2) and proliferative retinopathy (R3) at primary grading, agreement between the primary and secondary grader was 100%. Where there was disagreement between the primary and secondary grader for R1, only 2.6% (n=41) were upgraded by an ophthalmologist. The sensitivity and specificity for detecting R3 was 78.2% and 98.1%, respectively. None of the patients upgraded from any level of retinopathy to R3 required photocoagulation therapy. The observed kappa between the primary and secondary grader was 0.3223 (95% confidence interval 0.2937-0.3509), ie, fair agreement, and between the primary grader and ophthalmology for R3 was 0.5667 (95% confidence interval 0.4557-0.6123), ie, moderate agreement. CONCLUSION: These data provide information on the safety of a community optometry-based retinal screening program for screening as a primary and as a secondary grader. The level of agreement between the primary and secondary grader at a higher level of retinopathy (R2 and R3) was 100%. Sensitivity and specificity for R3 were 78.2% and 98.1%, respectively. None of the false-negative results required photocoagulation therapy. PMID- 25114497 TI - Intermittent acute angle closure glaucoma and chronic angle closure following topiramate use with plateau iris configuration. AB - This is a case report describing recurrent intermittent acute angle closure episodes in the setting of topiramate use in a female suffering from migraines. Despite laser peripheral iridotomy placement for the pupillary block component, and the discontinuation of topiramate, the acute angle closure did not resolve in the left eye with chronic angle closure and the patient required urgent trabeculectomy. The right eye responded to laser peripheral iridotomy immediately and further improved after the cessation of topiramate. While secondary angle closure glaucoma due to topiramate use has been widely reported, its effects in patients with underlying primary angle closure glaucoma have not been discussed. Our report highlights the importance of recognizing the often multifactorial etiology of angle closure glaucoma to help guide clinical management. PMID- 25114498 TI - Learning curve of sutureless transconjunctival 20-gauge vitrectomy. AB - BACKGROUND: To report the learning curve of transition from 20-gauge (20 G) conventional vitrectomy to a 20 G sutureless vitrectomy technique. MATERIALS AND METHODS: This is a retrospective descriptive case study of 32 eyes from 32 consecutive patients who underwent sutureless 20 G pars plana vitrectomy. A 20 G microvitreoretinal blade was introduced, beveled transconjunctivally, slowly, parallel with the limbus, creating a conjunctivoscleral tunnel incision. Study participants were divided into three groups, and surgical time, induced astigmatism, and complications were compared. RESULTS: Of 32 consecutive patients, there was no significant difference in induced astigmatism or maneuvering between the early learning curve and other groups. The true learning curve was the first three patients. There were three cases where suturing the sclerotomy was necessary: one port in each case, three of 32 cases (9.3%), or three of 96 ports (2.9%). CONCLUSION: There were no significant difficulties in surgical maneuvers while performing 20 g sutureless vitrectomy. PMID- 25114500 TI - A case of retinopathy of prematurity treated by pattern scan laser photocoagulation. AB - We experienced a case of retinopathy of prematurity that was successfully treated with pattern scan laser. Pattern scan laser treatment should be considered as one treatment option for Retinopathy of Prematurity. PMID- 25114499 TI - Relative sensitivity and specificity of 10-2 visual fields, multifocal electroretinography, and spectral domain optical coherence tomography in detecting hydroxychloroquine and chloroquine retinopathy. AB - BACKGROUND: The purpose of this study was to determine the relative sensitivity and specificity of 10-2 visual fields (10-2 VFs), multifocal electroretinography (mfERG), and spectral domain optical coherence tomography (SD-OCT) in detecting hydroxychloroquine retinopathy. METHODS: A total of 121 patients taking hydroxychloroquine (n=119) or chloroquine (n=2) with 10-2 VF, mfERG, and SD-OCT tests were retrospectively reviewed. Rates of test abnormality were determined. RESULTS: Retinopathy was present in 14 and absent in 107. Eleven of 14 (78.6%) patients with retinopathy were overdosed. Twelve (85.7%) had cumulative dosing greater than 1,000 g. The sensitivities of 10-2 VF, mfERG, and SD-OCT in detecting retinopathy were 85.7%, 92.9%, and 78.6%, respectively. The specificities of 10-2 VF, mfERG, and SD-OCT in detecting retinopathy were 92.5%, 86.9%, and 98.1%, respectively. Positive predictive values of 10-2 VF, mfERG, and SD-OCT in detecting retinopathy were less than 30% for all estimates of hydroxychloroquine retinopathy prevalence. Negative predictive values were >99% for all tests. CONCLUSION: Based on published estimates of hydroxychloroquine retinopathy prevalence, all three tests are most reliable when negative, allowing confident exclusion of retinopathy in patients taking <=6.5 mg/kg/day. Each test is less useful in allowing a confident diagnosis of retinopathy when positive, especially in patients taking <=6.5 mg/kg/day. PMID- 25114501 TI - Comparison of Optomap ultrawide-field imaging versus slit-lamp biomicroscopy for assessment of diabetic retinopathy in a real-life clinic. AB - PURPOSE: We aimed to assess the agreement between clinical assessment of diabetic retinopathy and Optomap ultrawide-field imaging (UWFI) in a real-life clinic setting. METHODS: Structured examination findings, from diabetic patients attending routine medical retina clinics in July 2011, were retrospectively compared with the grade obtained from Optomap UWFI images, graded independently by two ophthalmologists, taken at the same visit. RESULTS: A total of 84 eyes (42 patients) were examined, and 74 eyes (37 patients) were suitable for analysis. The hospital Eye Service slit-lamp biomicroscopy grades for retinopathy were: no diabetic retinopathy in zero eyes; background retinopathy in 21 eyes; preproliferative retinopathy in 34 eyes; and proliferative retinopathy in 19 eyes. For retinopathy, the agreement between the Optomap UWFI and clinical grading was moderate for both graders (kappa=0.57 and kappa=0.63), and there was almost perfect agreement between the two graders (kappa=0.92). The clinical grades for the presence of photocoagulation scars were: no photocoagulation scars in 46 eyes and photocoagulation scars visible in 28 eyes, indicating substantial agreement between the Optomap UWFI and clinical grading for both graders (kappa=0.73 and kappa=0.64). There were two instances where proliferative retinopathy was documented clinically but graded as preproliferative by both graders of Optomap UWFI. These were investigated, and neither patient required treatment, ie, the difference in retinopathy grade would not have affected the patient outcomes. CONCLUSION: This study demonstrated moderate agreement between Optomap UWFI and hospital slit-lamp biomicroscopy grading of patients' retinopathy in a real-life medical retina clinic setting. The authors believe that Optomap UWFI is, not only a very useful adjunct to clinical examination in terms of detection and recording of retinopathy, but also, could have a role in standalone "virtual" clinics. PMID- 25114502 TI - Artificial tears potpourri: a literature review. AB - Numerous brands and types of artificial tears are available on the market for the treatment of dysfunctional tear syndrome. Past literature has focused on comparing the components of these products on patient's clinical improvement. The wide array of products on the market presents challenges to both clinicians and patients when trying to choose between available tear replacement therapies. Different formulations affect patients based on etiology and severity of disease. In order to provide an unbiased comparison between available tear replacement therapies, we conducted a literature review of existing studies and National Institutes of Health clinical trials on commercially available, brand name artificial tears. Outcomes evaluated in each study, as well as the percent of patients showing clinical and symptomatic improvement, were analyzed. Fifty-one studies evaluating different brands of artificial tears, and their efficacy were identified. Out of the 51 studies, 18 were comparison studies testing brand name artificial tears directly against each other. Nearly all formulations of artificial tears provided significant benefit to patients with dysfunctional tear syndrome, but some proved superior to others. From the study data, a recommended treatment flowchart was derived. PMID- 25114503 TI - Apoptosis and the FLIP and NF-kappa B proteins as pharmacodynamic criteria for biosimilar TNF-alpha antagonists. AB - Various criteria are necessary to assess the efficacy and safety of biological medications in order to grant companies the right to register these medications with the appropriate bodies that regulate their sale. The imminent expiration of the patents on reference biological products which block the cytokine TNF-alpha (tumor necrosis factor-alpha) raises the possibility of bringing so-called biosimilars to the market (similar to the biologicals of reference products). This occurrence is inevitable, but criteria to adequately evaluate these medications are now needed. Even among controversy, there is a demand from publications correlating the pro-apoptotic mechanism of the original TNF-alpha antagonists (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol) in the treatment of rheumatoid arthritis and other diseases. In this article, the authors discuss the possibility of utilizing the pro-apoptotic effect correlated with the regulation of the anti-apoptotic proteins FLIP and NF kappaB as new criteria for analyzing the pharmacodynamics of possible biosimilar TNF-alpha antagonists which should be submitted to regulatory agencies for evaluation. PMID- 25114504 TI - The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences. AB - Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug-fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug-fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid. PMID- 25114505 TI - Pustular drug eruption due to Panax notoginseng saponins. AB - Panax notoginseng saponins (PNS) are a patented product in the People's Republic of China, and have extensive effects on the cardiovascular system. Here we report on four elderly patients (one male and three female) with drug eruption induced by PNS injection. All developed a sudden skin rash with pruritus from head to foot, and subsequently accepted hospitalization. In each case, PNS had been used for less than 1 week before appearance of the rash. No specific short-term medications or changes in diet or exposure to environmental factors immediately prior to appearance of the rash were identified. These four patients had some interesting features in common, ie, pustules, fever, and elevated circulating neutrophil counts, which required high-dose, long-term glucocorticoid therapy. To our knowledge, this is the first report of pustular drug eruption induced by PNS and provides a useful reference and warning for clinicians. PMID- 25114506 TI - Evaluation of the biological activity of novel monocationic fluoroaryl-2,2' bichalcophenes and their analogues. AB - A series of bichalcophene fluorobenzamidines 5a-e was synthesized from the corresponding mononitriles 4a-e via a direct reaction with lithium bis(trimethylsilyl)amide LiN(TMS)2 followed by de-protection with ethanolic HCl (gas). Bichalcophene fluorobenzonitriles 4a-e were prepared adopting a Stille coupling reaction between the bromo compounds 3a-c and 2-(tri-n butylstannyl)furan or analogues. As an approach to drug discovery, the structure antimutagenicity relationship of novel fluoroarylbichalcophenes was examined using the Ames Salmonella/microsomal assay. At nontoxic concentrations (10 and 20 MUM), all derivatives alone or in combination with sodium azide (NaN3; 2 MUg/plate) or benzo[a]pyrene (B[a]P; 20 MUM) in the presence of S9 mix were not mutagenic. The fluoroaryl derivatives significantly reduced the NaN3-induced and B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions. The recorded antimutagenic activity of fluoroaryl derivatives varied depending on the kind of mutagen and the exposure regimen. Monocationic fluoroarylbichalcophenes were superior to the corresponding mononitriles in reducing B[a]P-induced mutagenicity. Nevertheless, mononitriles were more active against NaN3, especially at low concentrations and under pre-exposure treatments. The antimutagenic activity was congruent with a high antioxidant activity that could promote the DNA repair system. The fluorine substitution changed the antimutagenic signature of bichalcophenes. Some of these compounds could be selected for further anticancer studies. PMID- 25114507 TI - Novel artificial cell microencapsulation of a complex gliclazide-deoxycholic bile acid formulation: a characterization study. AB - Gliclazide (G) is an antidiabetic drug commonly used in type 2 diabetes. It has extrapancreatic hypoglycemic effects, which makes it a good candidate in type 1 diabetes (T1D). In previous studies, we have shown that a gliclazide-bile acid mixture exerted a hypoglycemic effect in a rat model of T1D. We have also shown that a gliclazide-deoxycholic acid (G-DCA) mixture resulted in better G permeation in vivo, but did not produce a hypoglycemic effect. In this study, we aimed to develop a novel microencapsulated formulation of G-DCA with uniform structure, which has the potential to enhance G pharmacokinetic and pharmacodynamic effects in our rat model of T1D. We also aimed to examine the effect that DCA will have when formulated with our new G microcapsules, in terms of morphology, structure, and excipients' compatibility. Microencapsulation was carried out using the Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) at a ratio of 1:30, and G-DCA-SA (test) at a ratio of 1:3:30. Complete characterization of microcapsules was carried out. The new G-DCA-SA formulation was further optimized by the addition of DCA, exhibiting pseudoplastic-thixotropic rheological characteristics. The size of microcapsules remained similar after DCA addition, and these microcapsules showed no chemical interactions between the excipients. This was supported further by the spectral and microscopy studies, suggesting microcapsule stability. The new microencapsulated formulation has good structural properties and may be useful for the oral delivery of G in T1D. PMID- 25114509 TI - Antimycobacterial, antimicrobial, and biocompatibility properties of para aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites. AB - The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS Zn/Al LDH nanocomposites to treat tuberculosis. PMID- 25114508 TI - Potential roles of GPR120 and its agonists in the management of diabetes. AB - Free fatty acids (FFAs) serve not only as nutrients that provide energy but also as extracellular signaling molecules that manipulate intracellular physiological events through FFA receptors (FFARs) such as FFAR4. FFAR4 is also known as G protein coupled receptor 120 (GPR120). The main role of GPR120 is to elicit FFA regulation on metabolism homeostasis. GPR120 agonism correlates with prevention of the occurrence and development of metabolic disorders such as obesity and diabetes. GPR120 activation directly or indirectly inhibits inflammation, modulates hormone secretion from the gastrointestinal tract and pancreas, and regulates lipid and/or glucose metabolism in adipose, liver, and muscle tissues, which may help prevent obesity and diabetes. This review summarizes recent advances in physiological roles of GPR120 in preventing insulin resistance and protecting pancreatic islet function, and examines how resident GPR120 in the pancreas may be involved in modulating pancreatic islet function. PMID- 25114511 TI - Health state utilities associated with adult attention-deficit/hyperactivity disorder. AB - OBJECTIVES: With growing awareness of the importance of adult attention deficit/hyperactivity disorder (ADHD) treatment, cost-effectiveness analyses, including utilities, are needed to compare the value of treatment options. Although utilities have been reported for childhood ADHD, little is known about utilities representing adult ADHD. Therefore, the purpose of this study was to estimate utilities associated with adult ADHD. METHODS: Health-state descriptions of adult ADHD were drafted based on literature review, interviews with four clinicians, and clinical trial data. Health states were revised based on a pilot study with 26 participants. Final health states were rated in time trade-off interviews with general population respondents in London and Edinburgh, UK. RESULTS: A total of 158 participants completed interviews (mean age =47.0 years; 49.4% female; Edinburgh =80 participants). Mean (standard deviation [SD]) utilities were 0.82 (0.17), 0.68 (0.28), and 0.67 (0.28) for health states describing treatment responders (health state A), nonresponders (health state B), and untreated patients (health state C), respectively. Most participants rated health state A as preferable to B (n=92; 58.2%) and C (n=97; 61.4%). The majority rated B and C as equal (n=125; 79.1%). Paired Student's t-tests found that A had a significantly greater mean utility than B (t=10.0; P<0.0001) and C (t=10.2; P<0.0001). CONCLUSION: The current study provides utilities that may be used in cost-utility models of treatment for adult ADHD. Results reflected clear differences between health states representing treatment responders and nonresponders/untreated patients. Current utilities were comparable to those previously reported for childhood ADHD. PMID- 25114510 TI - Clinical utility of erlotinib for the treatment of non-small-cell lung cancer in Japanese patients: current evidence. AB - Gefitinib, an epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI), has been approved in Japan for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) based on Phase II clinical trials since 2002. Erlotinib, another EGFR-TKI, was also approved a few years thereafter. In 2004, activating mutations in the EGFR gene were discovered to be a predictive biomarker for EGFR TKI treatment, and gefitinib, which is not effective for patients with EGFR wild type NSCLC, has since been used only in patients with EGFR-mutated NSCLC. In contrast, erlotinib is potentially effective for the treatment of EGFR wild-type NSCLC. Similar to gefitinib, erlotinib is also effective for EGFR-mutated NSCLC and has been used as an initial treatment for patients with advanced EGFR-mutated NSCLC. Both gefitinib and erlotinib can be used in a Japanese clinical setting. The approved daily dose of erlotinib (150 mg) is equal to the maximum tolerated dose of erlotinib. In contrast, the daily dose of gefitinib has been set at 250 mg, which is approximately one-third of the maximum tolerated dose of gefitinib. Accordingly, a higher serum concentration can be achieved using erlotinib, compared with gefitinib. This advantage can be applied to the treatment of central nervous system metastases (brain metastasis and carcinomatous meningitis), the treatment of which is complicated by the difficulty drugs have penetrating the blood-brain barrier. Although patients with EGFR-mutated NSCLC respond dramatically to EGFR-TKIs, some patients have a poor response and the majority eventually undergo disease progression. To overcome such resistance, several novel treatment strategies, such as combination therapy and next generation EGFR-TKIs, have been attempted. PMID- 25114513 TI - Medication adherence: process for implementation. AB - Improving medication adherence is a critically important, but often enigmatic objective of patients, providers, and the overall health care system. Increasing medication adherence has the potential to reduce health care costs while improving care quality, patient satisfaction and health outcomes. While there are a number of papers that describe the benefits of medication adherence in terms of cost, safety, outcomes, or quality of life, there are limited reviews that consider how best to seamlessly integrate tools and processes directed at improving medication adherence. We will address processes for implementing medication adherence interventions with the goal of better informing providers and health care systems regarding the safe and effective use of medications. PMID- 25114512 TI - What puts heart failure patients at risk for poor medication adherence? AB - BACKGROUND: Medication nonadherence is a major cause of hospitalization in patients with heart failure (HF), which contributes enormously to health care costs. We previously found, using the World Health Organization adherence dimensions, that condition and patient level factors predicted nonadherence in HF. In this study, we assessed a wider variety of condition and patient factors and interactions to improve our ability to identify those at risk for hospitalization. MATERIALS AND METHODS: Medication adherence was measured electronically over the course of 6 months, using the Medication Event Monitoring System (MEMS). A total of 242 HF patients completed the study, and usable MEMS data were available for 218 (90.1%). Participants were primarily white (68.3%), male (64.2%), and retired (44.5%). Education ranged from 8-29 years (mean, 14.0 years; standard deviation, 2.9 years). Ages ranged from 30-89 years (mean, 62.8 years; standard deviation, 11.6 years). Analyses used adaptive methods based on heuristic searches controlled by cross-validation scores. First, individual patient adherence patterns over time were used to categorize patients in poor versus better adherence types. Then, risk factors for poor adherence were identified. Finally, an effective model for predicting poor adherence was identified based on identified risk factors and possible pairwise interactions between them. RESULTS: A total of 63 (28.9%) patients had poor adherence. Three interaction risk factors for poor adherence were identified: a higher number of comorbid conditions with a higher total number of daily medicines, older age with poorer global sleep quality, and fewer months since diagnosis of HF with poorer global sleep quality. Patients had between zero and three risk factors. The odds for poor adherence increased by 2.6 times with a unit increase in the number of risk factors (odds ratio, 2.62; 95% confidence interval, 1.78-3.86; P<0.001). CONCLUSION: Newly diagnosed, older HF patients with comorbid conditions, polypharmacy, and poor sleep are at risk for poor medication adherence. Interventions addressing these specific barriers are needed. PMID- 25114514 TI - Use of family member-based supervision in the management of patients with hypertension in rural China. AB - Medication nonadherence is a major problem in the management of hypertension. The aim of this study was to develop a family member-based supportive therapy for patients with hypertension to provide an affordable way to access essential health services and to ensure adequate control of blood pressure. This study applied a mixed methods approach using qualitative and quantitative study designs in Yangzhong County, a rural area in the People's Republic of China. Findings from indepth interviews demonstrated that the limited effects of traditional health education, a lack of professional advice regarding antihypertensive treatment, and age were related to a patient's adherence with regular blood pressure measurement and taking medication. We also performed a quantitative study, selecting two villages in Yangzhong County as study sites. A total of 188 patients with hypertension were invited to participate in a 6-month family member based intervention trial. The primary outcomes were the acceptability and feasibility of the intervention strategy. Secondary outcomes included medication adherence and changes in blood pressure. More than 75% of patients expressed a wish for external reminders, and 93.5% responded that they would accept the family member-based supervision. The patients preferred their spouse or a child as the supervisor. After the 6-month intervention, the proportion of patients with uncontrolled blood pressure decreased from 87.2% to 45.7%. This pilot study shows that external supervision by family members is acceptable and feasible for patients with hypertension; it also shows favorable effects with regard to improved treatment adherence and blood pressure control. Future randomized controlled trials with modified intervention measures are needed to validate this finding. PMID- 25114515 TI - Peer-driven contraceptive choices and preferences for contraceptive methods among students of tertiary educational institutions in Enugu, Nigeria. AB - PURPOSE: To describe the methods preferred for contraception, evaluate preferences and adherence to modern contraceptive methods, and determine the factors associated with contraceptive choices among tertiary students in South East Nigeria. METHODS: A questionnaire-based cross-sectional study of sexual habits, knowledge of contraceptive methods, and patterns of contraceptive choices among a pooled sample of unmarried students from the three largest tertiary educational institutions in Enugu city, Nigeria was done. Statistical analysis involved descriptive and inferential statistics at the 95% level of confidence. RESULTS: A total of 313 unmarried students were studied (194 males; 119 females). Their mean age was 22.5+/-5.1 years. Over 98% of males and 85% of females made their contraceptive choices based on information from peers. Preferences for contraceptive methods among female students were 49.2% for traditional methods of contraception, 28% for modern methods, 10% for nonpharmacological agents, and 8% for off-label drugs. Adherence to modern contraceptives among female students was 35%. Among male students, the preference for the male condom was 45.2% and the adherence to condom use was 21.7%. Multivariate analysis showed that receiving information from health personnel/media/workshops (odds ratio 9.54, 95% confidence interval 3.5-26.3), health science-related course of study (odds ratio 3.5, 95% confidence interval 1.3-9.6), and previous sexual exposure prior to university admission (odds ratio 3.48, 95% confidence interval 1.5-8.0) all increased the likelihood of adherence to modern contraceptive methods. CONCLUSION: An overwhelming reliance on peers for contraceptive information in the context of poor knowledge of modern methods of contraception among young people could have contributed to the low preferences and adherence to modern contraceptive methods among students in tertiary educational institutions. Programs to reduce risky sexual behavior among these students may need to focus on increasing the content and adequacy of contraceptive information held by people through regular health worker-led, on-campus workshops. PMID- 25114516 TI - Relationship between cognitive impairment and apparent diffusion coefficient values from magnetic resonance-diffusion weighted imaging in elderly hypertensive patients. AB - BACKGROUND: The purpose of this study was to determine a new method for the early diagnosis and assessment of mild cognitive impairment in elderly individuals with hypertension. Elderly hypertensive patients with cognitive impairment were assessed by the Montreal Cognitive Assessment (MoCA) and Clinical Dementia Rating Assessment (CDR). Cognitive results were compared to apparent diffusion coefficient (ADC) values from magnetic resonance-diffusion weighted imaging. METHODS: A total of 191 patients were categorized into four groups: a control group (normal cognition and no hypertension; n=20); a normal group (hypertension and normal cognition; n=33); an mild cognitive impairment group (n=80); and a vascular dementia group (n=58). The MoCA and CDR tests were used to determine cognition. ADC values in eight brain regions were calculated with magnetic resonance-diffusion weighted imaging. Other characteristics were evaluated, eg, blood pressure, MoCA, and CDR scores, and the comparisons of the four groups were made. RESULTS: The MoCA and CDR scores differed among the four groups (P<0.001). Systolic and diastolic blood pressure values increased as cognitive function declined (P<0.001). Cognitive function declined as ADC values increased, and they differed between elderly people with and without hypertension (P<0.001). Among elderly hypertensive participants, ADC values were significantly increased in the cortex and hippocampus. CONCLUSION: The MoCA and CDR tests were sufficiently sensitive to evaluate cognition. Blood pressure was closely related to cognition, as well as to functional and structural changes in the brain. These alterations were evidenced through changes in the ADC values and were most obvious in the cortex and hippocampus. Greater cognitive decline was observed in elderly participants with hypertension compared to those without. As hypertensive stage increased, greater ADC values were observed. PMID- 25114517 TI - Subjective well-being in Swedish active seniors and its relationship with physical activity and commonly available biomarkers. AB - BACKGROUND: Physical activity is claimed to be related to well-being and to a lower risk of cardiovascular disease. Therefore, the possible associations of well-being with physical activity and biomarkers of somatic health were studied in a sample of Swedish active seniors to determine the strength of these associations. METHODS: Three hundred and eighty-nine community-dwelling senior citizens (127 men and 262 women) of mean age 74 +/- 5 years were recruited for this cross-sectional population study. Serum samples were analyzed for lipoproteins and markers of inflammation. The Psychological General Well-Being (PGWB) index was used to measure subjective well-being. Physical activity was assessed by the International Physical Activity Questionnaire modified for the elderly. RESULTS: More than 50% of men and women rated their physical activity as high; in the women, there was a significant difference between the age groups (younger and older than the median age [median =74.1 years], respectively). The mean PGWB index indicates a high degree of subjective well-being in this group of Swedish seniors. Of the PGWB subdimensions, general health had the strongest positive relationship with physical activity (r (2)=5.4%). For the subdimensions of depressed mood, positive well-being, vitality, and PGWB index, physical activity had an r (2) <= 4%, while the contributions of sex, age, and biomarkers were minor. CONCLUSION: We have estimated the contribution of physical activity to the variance of subjective well-being in active seniors. Physical activity appears to play a greater role as a determinant of subjective well-being than do biomarkers of somatic health, especially in females, but most of the variance remained unaccounted for by the studied variables. PMID- 25114518 TI - Percutaneous coronary intervention in the elderly with ST-segment elevation myocardial infarction. AB - As a result of increased life expectancy, octogenarians constitute an increasing proportion of patients admitted to hospital for ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention is currently the treatment of choice for octogenarians presenting with STEMI. The recent literature on this topic has yielded controversial results, even though advances in drug-eluting stents and new types of antithrombotic agents are improving the management of STEMI and postoperative care. In this paper, we review the current status of percutaneous coronary intervention in the elderly with STEMI, including the reasons for their high mortality and morbidity, predictors of mortality, and strategies to improve outcomes. PMID- 25114519 TI - Interleukin-6 and interleukin-8 blood levels' poor association with the severity and clinical profile of ex-smokers with COPD. AB - BACKGROUND: The role of interleukins in the severity and clinical profile of chronic obstructive pulmonary disease (COPD) is not known, but evidence supports the contribution of systemic inflammation to disease pathophysiology. This study evaluated the relationship of serum biomarkers to the severity and clinical parameters of COPD. METHODS AND FINDINGS: Serum levels of high-sensitivity C reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured in 50 patients with stable COPD and in 16 controls. The levels of these biomarkers were compared with parameters of severity, such as the grading of flow obstruction using the recommendations of the Global initiative for chronic Obstructive Lung Disease, the BMI (body mass index), obstruction, dyspnea, exercise capacity (health index) index, the number of exacerbations within the last year, and peripheral oxygen saturation after the six-minute walk test, and with clinical parameters, such as bronchitis and non-bronchitis phenotypes, the number of associated comorbidities, and the smoking burden. COPD patients exhibited higher levels of IL-6 and IL-8 compared to the control group. Higher levels of IL-6 occurred in COPD groups with body mass index <21 kg/m(2), with more than two exacerbations in the past year, with a higher smoking burden, and with bronchitis. The increase in serum IL-8 was found only in the group with the highest number of exacerbations within the previous year. CONCLUSION: Increased IL-6 was mainly associated with smoking burden, in patients who had smoked for more than 30 pack-years and exhibited a bronchitis phenotype. No direct association was observed for both IL-6 and IL-8 blood levels with the severity of COPD in ex-smokers. PMID- 25114520 TI - Pulmonary function impairment in patients with combined pulmonary fibrosis and emphysema with and without airflow obstruction. AB - BACKGROUND: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is a recently described entity associating upper-lobe emphysema and lower-lobe fibrosis. We sought to evaluate differences in pulmonary function between CPFE patients with and without airflow obstruction. SUBJECTS AND METHODS: Thirty-one CPFE patients were divided into two groups according to the presence or absence of irreversible airflow obstruction based on spirometry (forced expiratory volume in 1 second/forced vital capacity <70% following inhalation of a beta2-agonist) as follows: CPFE patients with airflow obstruction (CPFE OB(+) group, n=11), and CPFE patients without airflow obstruction (CPFE OB(-) group, n=20). Pulmonary function, including respiratory impedance evaluated using impulse oscillometry and dynamic hyperinflation following metronome-paced incremental hyperventilation, was retrospectively analyzed in comparison with that observed in 49 chronic obstructive pulmonary disease (COPD) patients (n=49). RESULTS: In imaging findings, low-attenuation-area scores on chest high-resolution computed tomography, representing the degree of emphysema, were significantly lower in the CPFE OB(-) group than in the CPFE OB(+) and COPD groups. In contrast, the severity of pulmonary fibrosis was greater in the CPFE OB(-) group than in the CPFE OB(+) group. In pulmonary function, lung hyperinflation was not apparent in the CPFE OB(-) group. Impairment of diffusion capacity was severe in both the CPFE OB(-) and CPFE OB(+) groups. Impulse oscillometry showed that respiratory resistance was not apparent in the CPFE OB(-) group compared with the COPD group, and that easy collapsibility of small airways during expiration of tidal breath was not apparent in the CPFE OB(+) group compared with the COPD group. Dynamic hyperinflation following metronome-paced incremental hyperventilation was significantly greater in the COPD group than in the CPFE OB(-) group, and also tended to be greater in the CPFE OB(+) group than in the CPFE OB(-) group. CONCLUSION: The mechanisms underlying impairment of physiological function may differ among CPFE OB(+) patients, CPFE OB(-) patients, and COPD patients. CPFE is a heterogeneous disease, and may have distinct phenotypes physiologically and radiologically. PMID- 25114521 TI - Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol. AB - PURPOSE: In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD), an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted. METHODS: A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol. Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, St George's Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations. RESULTS: Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol). Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD. Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials. When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters), the following mean differences (95% confidence interval) were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, -0.005 (-0.077 to 0.067), and indacaterol 150 mcg versus olodaterol 5 mcg, 0.020 (-0.036 to 0.077); trials with concomitant tiotropium: indacaterol 150 mcg versus olodaterol 5 mcg, 0.000 (-0.043 to 0.042). In sensitivity analyses of the full network, results for change from baseline in trough FEV1 favored indacaterol, but this dataset suffered from trial design heterogeneity. For the other endpoints investigated, no statistically significant differences were found when analyzed in the full network. CONCLUSION: When compared under similar trial conditions, olodaterol and indacaterol have similar efficacy in patients with COPD. This research highlights the importance of considering the concomitant COPD medication when evaluating treatment effects in COPD. PMID- 25114522 TI - Self-assembled nanoparticles based on the c(RGDfk) peptide for the delivery of siRNA targeting the VEGFR2 gene for tumor therapy. AB - The clinical application of small interfering RNA (siRNA) has been restricted by their poor intracellular uptake, low serum stability, and inability to target specific cells. During the last several decades, a great deal of effort has been devoted to exploring materials for siRNA delivery. In this study, biodegradable, tumor-targeted, self-assembled peptide nanoparticles consisting of cyclo(Arg-Gly Asp-d-Phe-Lys)-8-amino-3,6-dioxaoctanoic acid-beta-maleimidopropionic acid (hereafter referred to as RPM) were found to be an effective siRNA carrier both in vitro and in vivo. The nanoparticles were characterized based on transmission electron microscopy, circular dichroism spectra, and dynamic light scattering. In vitro analyses showed that the RPM/VEGFR2-siRNA exhibited negligible cytotoxicity and induced effective gene silencing. Delivery of the RPM/VEGFR2 (zebrafish) siRNA into zebrafish embryos resulted in inhibition of neovascularization. Administration of RPM/VEGFR2 (mouse)-siRNA to tumor-bearing nude mice led to a significant inhibition of tumor growth, a marked reduction of vessels, and a down regulation of VEGFR2 (messenger RNA and protein) in tumor tissue. Furthermore, the levels of IFN-alpha, IFN-gamma, IL-12, and IL-6 in mouse serum, assayed via enzyme-linked immunosorbent assay, did not indicate any immunogenicity of the RPM/VEGFR2 (mouse)-siRNA in vivo. In conclusion, RPM may provide a safe and effective delivery vector for the clinical application of siRNAs in tumor therapy. PMID- 25114524 TI - Investigation of the mechanism of enhanced skin penetration by ultradeformable liposomes. AB - This study aimed to determine the mechanism by which ultradeformable liposomes (ULs) with terpenes enhance skin penetration for transdermal drug delivery of fluorescein sodium, using transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Skin treated with ULs containing d-limonene, obtained from in vitro skin penetration studies, was examined via TEM to investigate the effect of ULs on ultrastructural changes of the skin, and to evaluate the mechanism by which ULs enhance skin penetration. The receiver medium collected was analyzed by TEM and CLSM to evaluate the mechanism of the drug carrier system. Our findings revealed that ULs could enhance penetration by denaturing intracellular keratin, degrading corneodesmosomes, and disrupting the intercellular lipid arrangement in the stratum corneum. As inferred from the presence of intact vesicles in the receiver medium, ULs are also able to act as a drug carrier system. CLSM images showed that intact vesicles of ULs might penetrate the skin via a transappendageal pathway, potentially a major route of skin penetration. PMID- 25114523 TI - Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes. AB - Since the availability of recombinant human growth hormone (rhGH) enabled the application of human growth hormone both in clinical and research use in the 1980s, millions of patients were prescribed a daily injection of rhGH, but noncompliance rates were high. To address the problem of noncompliance, numerous studies have been carried out, involving: sustained-release preparations, prolonged half-life derivatives, new injectors that cause less pain, and other noninvasive delivery methods such as intranasal, pulmonary and transdermal deliveries. Some accomplishments have been made and launched already, such as the Nutropin Depot microsphere and injectors (Zomajet, Serojet, and NordiFlex). Here, we provide a review of the different technologies and illustrate the key points of these studies to achieve an improved rhGH product. PMID- 25114525 TI - Antibacterial properties of silver nanoparticles synthesized using Pulicaria glutinosa plant extract as a green bioreductant. AB - The antibacterial properties of nanoparticles (NPs) can be significantly enhanced by increasing the wettability or solubility of NPs in aqueous medium. In this study, we investigated the effects of the stabilizing agent on the solubility of silver NPs and its subsequent effect on their antimicrobial activities. Silver NPs were prepared using an aqueous solution of Pulicaria glutinosa plant extract as bioreductant. The solution also acts as a capping ligand. During this study, the antimicrobial activities of silver NPs, as well as the plant extract alone, were tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Micrococcus luteus. Silver NPs were prepared with various concentrations of the plant extract to study its effect on antimicrobial activity. Interestingly, various concentrations of P. glutinosa extract did not show any effect on the growth of tested bacteria; however, a significant effect on the antimicrobial property of plant extract capped silver NPs (Ag-NPs-PE) was observed. For instance, the half maximal inhibitory concentration values were found to decrease (from 4% to 21%) with the increasing concentrations of plant extract used for the synthesis of Ag-NPs-PE. These results clearly indicate that the addition of P. glutinosa extracts enhances the solubility of Ag-NPs-PE and, hence, increases their toxicity against the tested microorganisms. PMID- 25114526 TI - High gene delivery efficiency of alkylated low-molecular-weight polyethylenimine through gemini surfactant-like effect. AB - To our knowledge, the mechanism underlying the high transfection efficiency of alkylated low-molecular-weight polyethylenimine (PEI) is not yet well understood. In this work, we grafted branched PEI (molecular weight of 1,800 Da; bPEI1800) with lauryl chains (C12), and found that bPEI1800-C12 was structurally similar to gemini surfactant and could similarly assemble into micelle-like particles. Stability, cellular uptake, and lysosome escape ability of bPEI1800-C12/DNA polyplexes were all greatly enhanced after C12 grafting. bPEI1800-C12/DNA polyplexes exhibited significantly higher transfection efficiency than Lipofectamine 2000 in the presence of serum. Bioluminescence imaging showed that systemic injection of bPEI1800-C12/DNA polyplexes resulted in intensive luciferase expression in vivo and bioluminescence signals that could be detected even in the head. Altogether, the high transfection efficacy of bPEI1800-C12 was because bPEI1800-C12, being an analog of gemini surfactant, facilitated lysosome escape and induced the coil-globule transition of DNA to assemble into a highly organized micelle-like structure that showed high stability. PMID- 25114527 TI - Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy. AB - The potential of boron-containing lipids with three different structures, which were intended for use in boron neutron capture therapy, was investigated. All three types of boron lipids contained the anionic dodecaborate cluster as the headgroup. Their effects on two different tumor models in mice following intravenous injection were tested; for this, liposomes with boron lipid, distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing a polyethylene glycol lipid for steric protection, were administered intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell carcinoma and BALB/c mice for CT26/WT colon carcinoma). With the exception of one lipid (B-THF-14), the lipids were well tolerated, and no other animal was lost due to systemic toxicity. The lipid which led to death was not found to be much more toxic in cell culture than the other boron lipids. All of the lipids that were well tolerated showed hemorrhage in both tumor models within a few hours after administration. The hemorrhage could be seen by in vivo magnetic resonance and histology, and was found to occur within a few hours. The degree of hemorrhage depended on the amount of boron administered and on the tumor model. The observed unwanted effect of the lipids precludes their use in boron neutron capture therapy. PMID- 25114528 TI - Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides. AB - Self-administered topical microbicides or oral preexposure prophylaxis could be very helpful tools for all risk groups to decrease the human immunodeficiency virus (HIV)-1 infection rates. Up until now, antiretrovirals (ARVs) have been the most advanced microbicide candidates. Nevertheless, the majority of clinical trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane dendrimers, have been shown to be safe and effective compounds against HIV with great potential as topical microbicides. In addition, because most of the attempts to develop effective topical microbicides were unsuccessful, combinatorial strategies could be a valid approach when designing new microbicides. We evaluated various combinations of anionic carbosilane dendrimers with sulfated (G3-S16) and naphthyl sulfonated (G2-NF16) ended groups with different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed a synergistic or additive activity profile with zidovudine, efavirenz, and tenofovir in the majority of the combinations tested against the X4 and R5 tropic HIV-1 in cell lines, as well as in human primary cells. Therefore, the combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral potency of the individual compounds, and our findings support further clinical research on combinational approaches as potential microbicides to block the sexual transmission of HIV-1. PMID- 25114531 TI - Perspectives on perceived stigma and self-stigma in adult male patients with depression. AB - There are two principal types of stigma in mental illness, ie, "public stigma" and "self-stigma". Public stigma is the perception held by others that the mentally ill individual is socially undesirable. Stigmatized persons may internalize perceived prejudices and develop negative feelings about themselves. The result of this process is "self-stigma". Stigma has emerged as an important barrier to the treatment of depression and other mental illnesses. Gender and race are related to stigma. Among depressed patients, males and African-Americans have higher levels of self-stigma than females and Caucasians. Perceived stigma and self-stigma affect willingness to seek help in both genders and races. African-Americans demonstrate a less positive attitude towards mental health treatments than Caucasians. Religious beliefs play a role in their coping with mental illness. Certain prejudicial beliefs about mental illness are shared globally. Structural modeling indicates that conformity to dominant masculine gender norms ("boys don't cry") leads to self-stigmatization in depressed men who feel that they should be able to cope with their illness without professional help. These findings suggest that targeting men's feelings about their depression and other mental health problems could be a more successful approach to change help-seeking attitudes than trying to change those attitudes directly. Further, the inhibitory effect of traditional masculine gender norms on help-seeking can be overcome if depressed men feel that a genuine connection leading to mutual understanding has been established with a health care professional. PMID- 25114529 TI - 2'-(2-bromohexadecanoyl)-paclitaxel conjugate nanoparticles for the treatment of non-small cell lung cancer in an orthotopic xenograft mouse model. AB - A nanoparticle (NP) formulation with 2'-(2-bromohexadecanoyl)-paclitaxel (Br-16 PX) conjugate was developed in these studies for the treatment of non-small cell lung cancer (NSCLC). The lipophilic paclitaxel conjugate Br-C16-PX was synthesized and incorporated into lipid NPs where the 16-carbon chain enhanced drug entrapment in the drug delivery system and improved in vivo pharmacokinetics. The electron-withdrawing bromine group was used to facilitate the conversion of Br-C16-PX to paclitaxel at the tumor site. The developed system was evaluated in luciferase-expressing A549 cells in vitro and in an orthotopic NSCLC mouse model. The results demonstrated that the Br-C16-PX NPs had a higher maximum tolerated dose (75 mg/kg) than Taxol (19 mg/kg) and provided significantly longer median survival (88 days versus 70 days, P<0.05) in the orthotopic NSCLC model. An improved pharmacokinetic profile was observed for the Br-C16-PX NPs at 75 mg/kg compared to Taxol at 19 mg/kg. The area under the concentration versus time curve (AUC)0-96 h of Br-C16-PX from the NPs was 91.7 fold and 49.6-fold greater than Taxol in plasma and tumor-bearing lungs, respectively, which provided sustained drug exposure and higher antitumor efficacy in the NP-treated group. PMID- 25114532 TI - Caregiver burden and coping strategies in caregivers of patients with Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease (AD) causes considerable distress in caregivers who are continuously required to deal with requests from patients. Coping strategies play a fundamental role in modulating the psychologic impact of the disease, although their role is still debated. The present study aims to evaluate the burden and anxiety experienced by caregivers, the effectiveness of adopted coping strategies, and their relationships with burden and anxiety. METHODS: Eighty-six caregivers received the Caregiver Burden Inventory (CBI) and the State Trait Anxiety Inventory (STAI Y-1 and Y-2). The coping strategies were assessed by means of the Coping Inventory for Stressful Situations (CISS), according to the model proposed by Endler and Parker in 1990. RESULTS: The CBI scores (overall and single sections) were extremely high and correlated with dementia severity. Women, as well as older caregivers, showed higher scores. The trait anxiety (STAI Y-2) correlated with the CBI overall score. The CISS showed that caregivers mainly adopted task-focused strategies. Women mainly adopted emotion-focused strategies and this style was related to a higher level of distress. CONCLUSION: AD is associated with high distress among caregivers. The burden strongly correlates with dementia severity and is higher in women and in elderly subjects. Chronic anxiety affects caregivers who mainly rely on emotion-oriented coping strategies. The findings suggest providing support to families of patients with AD through tailored strategies aimed to reshape the dysfunctional coping styles. PMID- 25114533 TI - The relationship between insight and subjective experience in schizophrenia. AB - OBJECTIVES: To examine the relationship between level of insight and various subjective experiences for patients with schizophrenia. MATERIALS AND METHODS: Seventy-four patients with schizophrenia who were discharged from our hospital were evaluated. The level of insight into their illness and various subjective experiences were evaluated at discharge. We used the Scale to Assess Unawareness of Mental Disorder (SUMD) for evaluation of insight. In addition, five different rating scales were used to evaluate subjective experiences: Subjective Experience of Deficits in Schizophrenia (SEDS), Subjective Well-being under Neuroleptic drug treatment Short form (SWNS), Schizophrenia Quality of Life Scale (SQLS), Beck Depression Inventory (BDI), and the Drug Attitude Inventory (DAI)-30. RESULTS: The SWNS and the scores for awareness of mental disorder and awareness of the social consequences of mental disorder on SUMD showed a weak positive correlation. The DAI-30 showed a significant negative correlation with most general items on SUMD and a negative correlation between the subscale scores for the awareness and attribution of past symptoms. SEDS, SWNS, SQLS, and the BDI significantly correlated with the subscale scores for awareness of current symptoms on SUMD, and weakly correlated with the subscale scores for attribution of current negative symptoms. CONCLUSION: Awareness of subjective distress was related to awareness of having a mental disorder. Feeling subjective distress was related to awareness of current symptoms, as well as to the ability to attribute current negative symptoms to a mental disorder. Positive attitudes toward medication correlated with better general insight into the illness. PMID- 25114534 TI - Sleep quality changes in insomniacs and non-insomniacs after acute altitude exposure and its relationship with acute mountain sickness. AB - OBJECTIVE: We aimed to observe the changes in subjective sleep quality among insomniacs and non-insomniacs after acute ascending to 3,700 m and its possible relationship with acute mountain sickness (AMS). METHODS: A total of 600 adult men were recruited. Subjects' subjective sleep quality was evaluated by the Athens Insomnia Scale. AMS was assessed using the Lake Louise scoring system. Arterial oxygen saturation was measured. RESULTS: Despite insomnia resolution in only a few subjects, the prevalence of insomnia among insomniacs remained stable at 90% after rapid ascent to 3,700 m. However, among non-insomniacs, the prevalence of insomnia sharply increased to 32.13% in the first day of altitude exposure and progressively reduced to 4.26% by the 60th day of altitude stay. Moreover, the prevalences of insomnia symptoms decreased more markedly from day 1 to day 60 at 3,700 m among non-insomniacs than among insomniacs. At 3,700 m, the prevalence of AMS among insomniacs was 79.01%, 60.49%, and 32.10% on the first, third, and seventh days, respectively, which was significantly higher than that among non-insomniacs. Multivariate regression revealed that elevated Athens Insomnia Scale scores are an independent risk factor for AMS (adjusted odds ratio 1.388, 95% confidence interval: 1.314-1.464, P<0.001), whereas high arterial oxygen saturation and long duration of altitude exposure are protective factors against AMS. CONCLUSION: Our results suggest that the effect of high-altitude exposure on subjective sleep quality is more marked, but disappears more quickly, among non-insomniacs than among insomniacs, whereas AMS is especially common among insomniacs. Moreover, poor subjective sleep quality is a risk factor for AMS. PMID- 25114535 TI - Determinants of decision-to-intervention time in the management and therapeutic outcome of emergency gynecological surgeries in south east Nigeria. AB - BACKGROUND: Prompt and timely response in the management of gynecological surgical cases can significantly affect the therapeutic surgical outcome of patients in emergency situations. The aim of this study was to evaluate the decision-to-intervention time (DIT), its determinants, and the significance in the therapeutic outcome of emergency gynecological surgeries managed at a federal teaching hospital in south east Nigeria over an 18-month period. METHODS: This was a prospective descriptive study of 105 emergency gynecological cases managed at a federal teaching hospital over an 18-month period. Patients were recruited at the point of admission and followed up until discharge for outcome. Data were abstracted with a data entry pro forma and then analyzed with the Epi InfoTM statistical software version 7.0. RESULTS: The incidence of gynecological surgical emergencies was 5.1% of the total gynecological cases managed during the study period. The mean DIT was 4.25 (range 1.45-5.50) hours with delay in intervention, mainly due to delays in securing blood/blood products and other materials for resuscitation (46.7%) and a lack of finance (15.2%). Six maternal deaths were recorded, giving a case fatality ratio of 5.7%, while the commonest maternal complications associated with the delays were hemorrhage (61.9%) and the need for blood transfusion (57.1%), respectively. The risk ratio of losing >=1,000 mL of blood, anemia, hemorrhagic shock, and wound infection in those with DIT >=120 minutes was statistically greater and significant at 95% confidence interval. CONCLUSION: Inadequacies in health care services and policies due to poor infrastructure, organizational framework, and financing were the major determinants of the prolonged DIT and therapeutic outcomes. PMID- 25114537 TI - New drugs to treat multidrug-resistant tuberculosis: the case for bedaquiline. AB - Mycobacterium tuberculosis develops spontaneous resistance mutants to virtually every drug in use. Courses of therapy select for these mutants and drug-resistant organisms emerge. The development of drug-resistant organisms has reached the point that drug resistance now threatens to undermine global success against tuberculosis (TB). New drugs are needed. The last new class of drugs specifically developed for treatment of TB was the rifamycins over 40 years ago. New funding sources and the development of product development partnerships have energized the TB drug development effort. There are now more TB drugs in development than at any time in the past. The first of these drugs to be developed and marketed was bedaquiline. Bedaquiline has an entirely novel mechanism of action and so should be active against otherwise highly resistant organisms. It acts on the transmembrane component of adenosine triphosphate synthase and acts by preventing electron transport. This raises the exciting possibility that bedaquiline may be active against less metabolically active organisms. Drug-drug interactions between rifamycins and the cytochrome P450-3A system will limit bedaquiline's utility and create complexity in treatment regimens. In clinical trials, treatment with bedaquiline added to a background multidrug-resistant TB regimen was associated with earlier culture conversion and higher cure rates, but there were unexplained excess deaths in the bedaquiline arms of these trials. Food and Drug Administration approved bedaquiline for the treatment of multidrug-resistant TB when an effective treatment regimen cannot otherwise be provided. They required a black box warning about excess deaths and require that a phase III trial be completed. A planned Phase III trial is being reorganized. While bedaquiline is an exciting drug and marks a dramatic moment in the history of TB treatment, its ultimate place in the anti-TB drug armamentarium is unclear pending the Phase III trial and the development of other new drugs that are in the pipeline. PMID- 25114538 TI - Process of implementing collaborative care and its impacts on the provision of care and rehabilitation services to patients with a moderate or severe traumatic brain injury. AB - OBJECTIVE: The introduction of new services in a rehabilitation center is a unique opportunity to introduce a new model of care and services between two institutions. A hospital and a rehabilitation center experienced a clinical management model inspired by an American approach - collaborative care. The purpose of this study was to describe the implementation of this approach and to provide a perception of the quality of care and services provided to patients with moderate or severe traumatic brain injury and to their caregivers. MATERIALS AND METHODS: In this qualitative study, individual semistructured interviews were conducted with patients and their caregivers in the hospital and rehabilitation center where the patients were treated. Individual semistructured interviews were conducted with administrators, and two focus groups were held with clinicians before and after the implementation. RESULTS AND CONCLUSION: Ten days' waiting time were saved with the collaborative approach. Implementing the collaborative care approach has been found to have several benefits, including improved communication, coordination of services between institutions, and better preparation, awareness, and involvement of patients and their families. Administrators, clinicians, patients, and caregivers expressed their opinions on the organization of care and services, the needs and expectations of patients and their caregivers, their participation in terms of roles and responsibilities, their perception of continuity of care, their satisfaction with the care process, and their suggestions for improvements. PMID- 25114536 TI - Optimal management of renal artery fibromuscular dysplasia. AB - Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory angiopathy of unknown cause affecting medium-sized (most commonly renal) arteries and causing renovascular hypertension. The most common medial multifocal type of FMD (with the "string of beads" appearance) is more than four times more prevalent in females than in males. FMD accounts for up to 10% of cases of renovascular hypertension. Compared with patients with atherosclerotic renal artery stenosis, patients with FMD are younger, have fewer risk factors for atherosclerosis, and a lower occurrence of atherosclerosis in other vessels. The etiology is multifactorial, including vessel wall ischemia and smoking, as well as hormonal and genetic factors. Intra-arterial digital subtraction angiography is still the gold standard for exclusion or confirmation of renal artery stenosis caused by FMD, at least in young patients, who more often have lesions in branches of the renal artery. For FMD patients with atherosclerosis and those who are older (>50 55 years), significant renal artery stenosis may be confirmed or excluded with ultrasonography. The FMD lesion is typically truncal or distal, whereas atherosclerotic lesions are more often proximal or ostial. Treatment options are medical, endovascular (percutaneous transluminal renal angioplasty [PTRA]), and surgical. Invasive treatment should be considered when hypertension cannot be controlled with antihypertensive drugs and in patients with impaired renal function or ischemic nephropathy. PTRA has become the treatment of choice and normally yields good results, especially in unifocal disease and young patients. Pressure gradients are normally completely abolished, and there is no indication for stent placement. Surgical revascularization is indicated after PTRA complications; thrombosis, perforation, progressive dissection, repeated PTRA failure or restenosis. Centralization of handling is recommended. PMID- 25114541 TI - Mathematical Modeling and Data Analysis of NMR Experiments using Hyperpolarized (13)C Metabolites. AB - Rapid-dissolution dynamic nuclear polarization (DNP) has made significant impact in the characterization and understanding of metabolism that occurs on the sub minute timescale in several diseases. While significant efforts have been made in developing applications, and in designing rapid-imaging radiofrequency (RF) and magnetic field gradient pulse sequences, very few groups have worked on implementing realistic mathematical/kinetic/relaxation models to fit the emergent data. The critical aspects to consider when modeling DNP experiments depend on both nuclear magnetic resonance (NMR) and (bio)chemical kinetics. The former constraints are due to the relaxation of the NMR signal and the application of 'read' RF pulses, while the kinetic constraints include the total amount of each molecular species present. We describe the model-design strategy we have used to fit and interpret our DNP results. To our knowledge, this is the first report on a systematic analysis of DNP data. PMID- 25114540 TI - Safety and efficacy of gadobutrol-enhanced MRI in patients aged under 2 years-a single-center, observational study. AB - Gadobutrol is a 1-molar gadolinium-based contrast agent with well-characterized safety and efficacy for magnetic resonance imaging (MRI) in adults and children >= 2 years old. This observational study assessed gadobutrol-enhanced MRI in children < 2 years of age. Sixty infants (mean age 11.1 months) underwent MRI using gadobutrol at standard dose of 0.1 mL/kg (0.1 mmol/kg) body weight. MRI examinations included brain, spine, and neck (n = 24), subcutaneous soft tissues (n = 14), chest, abdomen, and pelvis (n = 12), musculoskeletal system (n = 7) and vascular system (n = 3). No patients experienced adverse events related to gadobutrol injection. In 57 patients with confirmed diagnoses, gadobutrol enhanced MRI provided findings consistent with confirmed pathologies. This study indicates that gadobutrol at a standard dose for MRI is safe in patients aged < 2 years and provides diagnostic information for multiple pathologies. PMID- 25114539 TI - Design, implementation, and evaluation of a pediatric and adolescent type 2 diabetes management program at a tertiary pediatric center. AB - Global rates of type 2 diabetes in children and adolescents have increased significantly over the past three decades. Type 2 diabetes is a relatively new disease in this age group, and there is a dearth of information about how to structure treatment programs to manage its comorbidities and complications. In this paper, we describe the design and implementation of a personalized multidisciplinary, family-centered, pediatric and adolescent type 2 diabetes program at a tertiary pediatric center in Hamilton, Ontario, Canada. We report the process of designing and implementing such a program, and show that this multidisciplinary program led to improvement in glycated hemoglobin (n=17, 8% at baseline versus 6.4% at 1 year, 95% confidence interval (0.1-0.28), P-value <0.0001) and stabilized body mass index, with lowered C-peptide and no change in fitness or metabolic biomarkers of lipid metabolism and liver function. As type 2 diabetes becomes more prevalent in youth, the need for programs that successfully address the complex nature of this disease is central to its management and to mitigate its long-term adverse outcomes. PMID- 25114542 TI - Effect of object orientation angle on t2* image and reconstructed magnetic susceptibility: numerical simulations. AB - The magnetic field resulting from material magnetization in magnetic resonance imaging (MRI) has an object orientation effect, which produces an orientation dependence for acquired T2* images. On one hand, the orientation effect can be exploited for object anisotropy investigation (via multi-angle imaging); on the other hand, it is desirable to remove the orientation dependence using magnetic susceptibility reconstruction. In this report, we design a stick-star digital phantom to simulate multiple orientations of a stick-like object and use it to conduct various numerical simulations. Our simulations show that the object orientation effect is not propagated to the reconstructed magnetic susceptibility distribution. This suggests that accurate susceptibility reconstruction methods should be largely orientation independent. PMID- 25114544 TI - MR Spectroscopic Imaging of Peripheral Zone in Prostate Cancer Using a 3T MRI Scanner: Endorectal versus External Phased Array Coils. AB - Magnetic resonance spectroscopic imaging (MRSI) detects alterations in major prostate metabolites, such as citrate (Cit), creatine (Cr), and choline (Ch). We evaluated the sensitivity and accuracy of three-dimensional MRSI of prostate using an endorectal compared to an external phased array "receive" coil on a 3T MRI scanner. Eighteen patients with prostate cancer (PCa) who underwent endorectal MR imaging and proton (1H) MRSI were included in this study. Immediately after the endorectal MRSI scan, the PCa patients were scanned with the external phased array coil. The endorectal coil-detected metabolite ratio [(Ch+Cr)/Cit] was significantly higher in cancer locations (1.667 +/- 0.663) compared to non-cancer locations (0.978 +/- 0.420) (P < 0.001). Similarly, for the external phased array, the ratio was significantly higher in cancer locations (1.070 +/- 0.525) compared to non-cancer locations (0.521 +/- 0.310) (P < 0.001). The sensitivity and accuracy of cancer detection were 81% and 78% using the endorectal 'receive' coil, and 69% and 75%, respectively using the external phased array 'receive' coil. PMID- 25114545 TI - Understanding the morphological mismatch between magnetic susceptibility source and t2* image. AB - BACKGROUND AND PURPOSE: Recent research has shown that a T2* image (either magnitude or phase) is not identical to the internal spatial distribution of a magnetic susceptibility (chi) source. In this paper, we examine the reasons behind these differences by looking into the insights of T2*-weighted magnetic resonance imaging (T2*MRI) and provide numerical characterizations of the source/image mismatches by numerical simulations. METHODS: For numerical simulations of T2*MRI, we predefine a 3D chi source and calculate the complex valued T2* image by intravoxel dephasing in presence and absence of diffusion. We propose an empirical alpha-power model to describe the overall source/image transformation. For a Gaussian-shaped chi source, we numerically characterize the source/image morphological mismatch in terms of spatial correlation and FWHM (full width at half maximum). RESULTS: In theory, we show that the chi-induced fieldmap is morphologically different from the chi source due to dipole effect, and the T2* magnitude image is related to the fieldmap by a quadratic transformation in the small phase angle regime, which imposes an additional morphological change. The numerical simulations with a Gaussian-shaped chi source show that a T2* magnitude image may suffer an overall source/image morphological shrinkage of 20% to 25% and that the T2* phase image is almost identical to the fieldmap thus maintaining a morphological mismatch from the chi source due to dipole effect. CONCLUSION: The morphological mismatch between a bulk chi source and its T2* image is caused by the 3D convolution during tissue magnetization (dipole effect), the nonlinearity of the T2* magnitude and phase calculation, and the spin diffusion effect. In the small phase angle regime, the T2* magnitude exhibits an overall morphological shrinkage, and the T2* phase image suffers a dipole effect but maintains the chi-induced fieldmap morphology. PMID- 25114546 TI - Magnetic Resonance Imaging-derived Flow Parameters for the Analysis of Cardiovascular Diseases and Drug Development. AB - Nuclear magnetic resonance (NMR) allows for fast, accurate and noninvasive measurement of fluid flow in restricted and non-restricted media. The results of such measurements may be possible for a very small B 0 field and can be enhanced through detailed examination of generating functions that may arise from polynomial solutions of NMR flow equations in terms of Legendre polynomials and Boubaker polynomials. The generating functions of these polynomials can present an array of interesting possibilities that may be useful for understanding the basic physics of extracting relevant NMR flow information from which various hemodynamic problems can be carefully studied. Specifically, these results may be used to develop effective drugs for cardiovascular-related diseases. PMID- 25114543 TI - Magnetic resonance in the detection of breast cancers of different histological types. AB - Breast cancer incidence is increasing worldwide. Early detection is critical for long-term patient survival, as is monitoring responses to chemotherapy for management of the disease. Magnetic resonance imaging and spectroscopy (MRI/MRS) has gained in importance in the last decade for the diagnosis and monitoring of breast cancer therapy. The sensitivity of MRI/MRS for anatomical delineation is very high and the consensus is that MRI is more sensitive in detection than x-ray mammography. Advantages of MRS include delivery of biochemical information about tumor metabolism, which can potentially assist in the staging of cancers and monitoring responses to treatment. The roles of MRS and MRI in screening and monitoring responses to treatment of breast cancer are reviewed here. We rationalize how it is that different histological types of breast cancer are differentially detected and characterized by MR methods. PMID- 25114548 TI - Measuring restriction sizes using diffusion weighted magnetic resonance imaging: a review. AB - This article reviews a new concept in magnetic resonance as applied to cellular and biological systems. Diffusion weighted magnetic resonance imaging can be used to infer information about restriction sizes of samples being measured. The measurements rely on the apparent diffusion coefficient changing with diffusion times as measurements move from restricted to free diffusion regimes. Pulsed gradient spin echo (PGSE) measurements are limited in the ability to shorten diffusion times and thus are limited in restriction sizes which can be probed. Oscillating gradient spin echo (OGSE) measurements could provide shorter diffusion times so smaller restriction sizes could be probed. PMID- 25114547 TI - Contrast-enhanced magnetic resonance imaging in pediatric patients: review and recommendations for current practice. AB - Magnetic resonance imaging (MRI), frequently with contrast enhancement, is the preferred imaging modality for many indications in children. Practice varies widely between centers, reflecting the rapid pace of change and the need for further research. Guide-line changes, for example on contrast-medium choice, require continued practice reappraisal. This article reviews recent developments in pediatric contrast-enhanced MRI and offers recommendations on current best practice. Nine leading pediatric radiologists from internationally recognized radiology centers convened at a consensus meeting in Bordeaux, France, to discuss applications of contrast-enhanced MRI across a range of indications in children. Review of the literature indicated that few published data provide guidance on best practice in pediatric MRI. Discussion among the experts concluded that MRI is preferred over ionizing-radiation modalities for many indications, with advantages in safety and efficacy. Awareness of age-specific adaptations in MRI technique can optimize image quality. Gadolinium-based contrast media are recommended for enhancing imaging quality. The choice of most appropriate contrast medium should be based on criteria of safety, tolerability, and efficacy, characterized in age-specific clinical trials and personal experience. PMID- 25114552 TI - Chemo-enzymatic synthesis of glycolyl-ester-linked taxol-monosaccharide conjugate and its drug delivery system using hepatitis B virus envelope L bio-nanocapsules. AB - Chemo-enzymatic synthesis of glycolyl-ester-linked taxol-glucose conjugate, ie, 7 glycolyltaxol 2"-O-alpha-D-glucoside, was achieved by using alpha-glucosidase as a biocatalyst. The water-solubility of 7-glycolyltaxol 2"-O-alpha-D-glucoside (21 MUM) was 53 fold higher than that of taxol. The hepatitis B virus envelope L particles (bio-nanocapsules) are effective for delivering 7-glycolyltaxol 2"-O alpha-D-glucoside to human hepatocellular carcinoma NuE cells. PMID- 25114549 TI - MRS-based Metabolomics in Cancer Research. AB - Metabolomics is a relatively new technique that is gaining importance very rapidly. MRS-based metabolomics, in particular, is becoming a useful tool in the study of body fluids, tissue biopsies and whole organisms. Advances in analytical techniques and data analysis methods have opened a new opportunity for such technology to contribute in the field of diagnostics. In the MRS approach to the diagnosis of disease, it is important that the analysis utilizes all the essential information in the spectra, is robust, and is non-subjective. Although some of the data analytic methods widely used in chemical and biological sciences are sketched, a more extensive discussion is given of a 5-stage Statistical Classification Strategy. This proposes powerful feature selection methods, based on, for example, genetic algorithms and novel projection techniques. The applications of MRS-based metabolomics in breast cancer, prostate cancer, colorectal cancer, pancreatic cancer, hepatobiliary cancers, gastric cancer, and brain cancer have been reviewed. While the majority of these applications relate to body fluids and tissue biopsies, some in vivo applications have also been included. It should be emphasized that the number of subjects studied must be sufficiently large to ensure a robust diagnostic classification. Before MRS-based metabolomics can become a widely used clinical tool, however, certain challenges need to be overcome. These include manufacturing user-friendly commercial instruments with all the essential features, and educating physicians and medical technologists in the acquisition, analysis, and interpretation of metabolomics data. PMID- 25114550 TI - In vivo monitoring of natural killer cell trafficking during tumor immunotherapy. AB - Natural killer (NK) cells are a crucial part of the innate immune system and play critical roles in host anti-viral, anti-microbial, and antitumor responses. The elucidation of NK cell biology and their therapeutic use are actively being pursued with 200 clinical trials currently underway. In this review, we outline the role of NK cells in cancer immunotherapies and summarize current noninvasive imaging technologies used to track NK cells in vivo to investigate mechanisms of action, develop new therapies, and evaluate efficacy of adoptive transfer. PMID- 25114554 TI - Plant-based Paste Fermented by Lactic Acid Bacteria and Yeast: Functional Analysis and Possibility of Application to Functional Foods. AB - A plant-based paste fermented by lactic acid bacteria and yeast (fermented paste) was made from various plant materials. The paste was made of fermented food by applying traditional food-preservation techniques, that is, fermentation and sugaring. The fermented paste contained major nutrients (carbohydrates, proteins, and lipids), 18 kinds of amino acids, and vitamins (vitamin A, B1, B2, B6, B12, E, K, niacin, biotin, pantothenic acid, and folic acid). It contained five kinds of organic acids, and a large amount of dietary fiber and plant phytochemicals. Sucrose from brown sugar, used as a material, was completely resolved into glucose and fructose. Some physiological functions of the fermented paste were examined in vitro. It was demonstrated that the paste possessed antioxidant, antihypertensive, antibacterial, anti-inflammatory, anti-allergy and anti tyrosinase activities in vitro. It was thought that the fermented paste would be a helpful functional food with various nutrients to help prevent lifestyle diseases. PMID- 25114551 TI - Dying for Good: Virus-Bacterium Biofilm Co-evolution Enhances Environmental Fitness. AB - Commonly used in biotechnology applications, filamentous M13 phage are non-lytic viruses that infect E. coli and other bacteria, with the potential to promote horizontal gene transfer in natural populations with synthetic biology implications for engineering community systems. Using the E. coli strain TG1, we have investigated how a selective pressure involving elevated levels of toxic chromate, mimicking that found in some superfund sites, alters population dynamics following infection with either wild-type M13 phage or an M13-phage encoding a chromate reductase (Gh-ChrR) capable of the reductive immobilization of chromate (ie, M13-phageGh-ChrR). In the absence of a selective pressure, M13 phage infection results in a reduction in bacterial growth rate; in comparison, in the presence of chromate there are substantial increases in both cellular killing and biomass formation following infection of E. coli strain TG1with M13 phageGh-ChrR that is dependent on chromate-reductase activity. These results are discussed in terms of community structures that facilitate lateral gene transfer of beneficial traits that enhance phage replication, infectivity, and stability against environmental change. PMID- 25114553 TI - Chemo-enzymatic synthesis of ester-linked 2-phenylindole-3-carboxaldehyde monosaccharide conjugate as potential prodrug. AB - Chemo-enzymatic synthesis of ester-linked 2-phenylindole-3-carboxaldehyde-glucose conjugate (2-phenylindole-3-carboxyl-10"-O-beta-D-glucosyl ester) was achieved by using plant cell cultures as biocatalysts. The anticancer agent, 2-phenylindole-3 carboxaldehyde, induced apoptosis in cells, whereas 2-phenylindole-3-carboxyl-10" O-beta-D-glucosyl ester showed no cytotoxicity and induced no apoptosis. PMID- 25114555 TI - The impact of a diabetes self-management education program provided through a telemedicine link to rural california health care clinics. AB - BACKGROUND: This project investigated the impact of a DM self-management education program provided through a telemedicine link at nine rural health clinics in Northern California. METHODS: Two hundred thirty nine patients were provided with a single 2-hour class on DM delivered through a live televideo connection. Patients provided pre-intervention information on: demographics and overall health, self-care behaviors, and knowledge about DM. All participants completed a post-education survey on knowledge and self-care behaviors. RESULTS: There was a significant decrease in the number of patients who felt overwhelmed with their DM; pre-intervention 18.8%; post-intervention 5.4% (P < 0.0001). Patients increased the number of days they exercised; pre-intervention 3.4 days; post-intervention 3.9 days (P = 0.02). Patients increased the number of days they checked their feet; pre-intervention 4.2 days; post-intervention 5.6 days (P < 0.01). Knowledge about DM improved over the study period (P < 0.01). CONCLUSIONS: A single 2-hour class on DM administered through a telemedicine link to patients in rural health clinics resulted in feeling less overwhelmed, more knowledgeable about DM, and demonstrated an increase in self-care behavior; ie, exercise and foot care. PMID- 25114556 TI - Quality of health assistants in primary health centres in rural maharashtra, India. AB - INTRODUCTION: Health assistants are important functionaries of the primary health care system in India. Their role is supervision of field-based services among other things. A quality assurance mechanism for these health assistants is lacking. The present study was undertaken with the objectives of developing a tool to assess the quality of health assistants in primary health centres (PHCs) and to assess their quality using this tool. METHODOLOGY: Health assistants from three PHCs in the Wardha district of India were observed for a year using a tool developed from primary health care management Aavancement program modules. Data was collected by direct observation, interview, and review of records for quality of activities. RESULTS: Staff strength of health assistants was 87.5%. None of the health assistants were clear about their job descriptions. A supervisory schedule for providing supportive supervision to auxiliary nurse midwives (ANMs) was absent; most field activities pertaining to maternal and child health received poor focus. Monthly meetings lacked a clear agenda, and comments on quality improvement of services provided by the ANMs were missing. CONCLUSION: Continuous training with sensitization on quality issues is required to improve the unsatisfactory quality. PMID- 25114558 TI - Management options for patients with chronic back pain without an etiology. AB - The treatment and management of low back pain is complex when there is no specific etiology such as cancer, fracture, or herniated disc. An organized approach to management that follows evidence based guidelines will facilitate care in a problem that reflects a lifetime prevalence of over 70 percent. The purpose of this review is to present a guideline to care for a common disabling process with a very heterogeneous etiology. PMID- 25114559 TI - Narcotics in rheumatology. AB - Patients with rheumatic conditions often suffer from related chronic pain. When first-line traditional medications such as acetaminophen and anti-inflammatory medications do not suffice, then other options are needed. The traditional medications may ultimately not provide sufficient pain relief, or alternatively, they can pose as a contraindication due to underlying hypertension, renal, and/or hepatic disease. Therefore, narcotics are an alluring alternative, which if used in a multidisciplinary and systematic approach to the patient, can prove to be quite beneficial in the lives of these patients. PMID- 25114557 TI - Behavioral lifestyle intervention in the treatment of obesity. AB - This article provides an overview of research regarding adult behavioral lifestyle intervention for obesity treatment. We first describe two trials using a behavioral lifestyle intervention to induce weight loss in adults, the Diabetes Prevention Program (DPP) and the Look AHEAD (Action for Health in Diabetes) trial. We then review the three main components of a behavioral lifestyle intervention program: behavior therapy, an energy- and fat-restricted diet, and a moderate- to vigorous-intensity physical activity prescription. Research regarding the influence of dietary prescriptions focusing on macronutrient composition, meal replacements, and more novel dietary approaches (such as reducing dietary variety and energy density) on weight loss is examined. Methods to assist with meeting physical activity goals, such as shortening exercise bouts, using a pedometer, and having access to exercise equipment within the home, are reviewed. To assist with improving weight loss outcomes, broadening activity goals to include resistance training and a reduction in sedentary behavior are considered. To increase the accessibility of behavioral lifestyle interventions to treat obesity in the broader population, translation of efficacious interventions such as the DPP, must be undertaken. Translational studies have successfully altered the DPP to reduce treatment intensity and/or used alternative modalities to implement the DPP in primary care, worksite, and church settings; several examples are provided. The use of new methodologies or technologies that provide individualized treatment and real-time feedback, and which may further enhance weight loss in behavioral lifestyle interventions, is also discussed. PMID- 25114561 TI - Patient-Reported Outcomes (PROs) and Patient-Reported Outcome Measures (PROMs). AB - In recent years, there has been an increased focus on placing patients at the center of health care research and evaluating clinical care in order to improve their experience and ensure that research is both robust and of maximum value for the use of medicinal products, therapy, or health services. This paper provides an overview of patients' involvement in clinical research and service evaluation along with its benefits and limitations. We describe and discuss patient-reported outcomes (PROs) and patient-reported outcome measures (PROMs), including the trends in current research. Both the patient-reported experiences measures (PREMs) and patient and public involvement (PPI) initiative for including patients in the research processes are also outlined. PROs provide reports from patients about their own health, quality of life, or functional status associated with the health care or treatment they have received. PROMs are tools and/or instruments used to report PROs. Patient report experiences through the use of PREMs, such as satisfaction scales, providing insight into the patients' experience with their care or a health service. There is increasing international attention regarding the use of PREMS as a quality indicator of patient care and safety. This reflects the ongoing health service commitment of involving patients and the public within the wider context of the development and evaluation of health care service delivery and quality improvement. PMID- 25114562 TI - Age-friendly primary health care: an assessment of current service provision for older adults in Hong Kong. AB - There has been no study evaluating whether primary care services are sufficiently oriented towards the older population in Hong Kong, particularly those with increasing frailty. Since primary care is a key first interface in promotion and maintenance of health in older people, an assessment of the age-friendliness of service provisions is of critical importance in optimizing the health of aging populations. The age-friendliness of primary care services for older people was assessed using focus groups of elderly people and also of service providers who care for them. Discussion content was based on the WHO guidelines for age friendly primary care in the following areas: Information, education and training, community-based health care management systems, and the physical environment. Desirable improvements were identified in all domains. The findings underscore the need for wider dissemination of health care needs of older people in the primary care setting. PMID- 25114560 TI - Reducing the risk of harm from medication errors in children. AB - MEDICATION ERRORS AFFECT THE PEDIATRIC AGE GROUP IN ALL SETTINGS: outpatient, inpatient, emergency department, and at home. Children may be at special risk due to size and physiologic variability, limited communication ability, and treatment by nonpediatric health care providers. Those with chronic illnesses and on multiple medications may be at higher risk of experiencing adverse drug events. Some strategies that have been employed to reduce harm from pediatric medication errors include e-prescribing and computerized provider order entry with decision support, medication reconciliation, barcode systems, clinical pharmacists in medical settings, medical staff training, package changes to reduce look alike/sound-alike confusion, standardization of labeling and measurement devices for home administration, and quality improvement interventions to promote nonpunitive reporting of medication errors coupled with changes in systems and cultures. Future research is needed to measure the effectiveness of these preventive strategies. PMID- 25114563 TI - Behavioral interventions associated with smoking cessation in the treatment of tobacco use. AB - Tobacco smoke is the leading cause of preventable premature death worldwide. While the majority of smokers would like to stop, the habitual and addictive nature of smoking makes cessation difficult. Clinical guidelines suggest that smoking cessation interventions should include both behavioural support and pharmacotherapy (e.g. nicotine replacement therapy). This commentary paper focuses on the important role of behavioural interventions in encouraging and supporting smoking cessation attempts. Recent developments in the field are discussed, including 'cut-down to quit', the behaviour change techniques taxonomy (BCTT) and very brief advice (VBA) on smoking. The paper concludes with a discussion of the important role that health professionals can and should play in the delivery of smoking cessation interventions. PMID- 25114564 TI - Maintaining a Sufficient and Quality Physician Workforce: The Role of For-profit Medical Schools. AB - Currently, in the United States there is a significant physician workforce shortage. This problem is likely to persist as there is no quick solution. The nature of this shortage is complex and involves factors such as an absolute physician shortage, as well as physician shortages in primary care and certain specialty care areas. In addition, there is a misdistribution of physicians to medically underserved areas and populations. The medical education system trains medical school graduates that eventually feed the physician workforce. However, several factors are in place which ultimately limits the effectiveness of this system in providing an appropriate workforce to meet the population demands. For profit medical schools have been in existence in and around the continental US for many years and some authors have suggested that they may be a major contributor to the physician workforce shortage. There is currently one for profit medical school in the US, however the majority exist in the Caribbean. The enrollment in and number of these schools have grown to partially meet the ever growing demand for an increase in medical school graduates and they continue to provide a large number of graduates who return to the US for postgraduate medical training and, ultimately, increase the physician workforce. The question is whether this source will benefit the workforce quality and quantity needs of our growing and aging population. PMID- 25114565 TI - Adolescent sleep and cellular phone use: recent trends and implications for research. AB - Adolescent sleep needs range from 8.5-10 hours per night, with older adolescents requiring less sleep than younger adolescents. On average, however, American adolescents receive between 7.5-8.5 hours of sleep per night, with many sleeping fewer than 6.5 hours on school nights. Cellular phone use is emerging as an important factor that interferes with both sleep quality and quantity, particularly as smartphones become more widely available to teens. This review paper has three objectives. First, we will describe adolescent sleep patterns and the effects of sleep deprivation on adolescent physical and mental health. Second, we will describe current trends in technology use among adolescents, making associations to how technology impacts sleep. Lastly, we will discuss some of the methodological barriers of conducting sleep and technology research with adolescents and young adults and offer suggestions for overcoming those barriers. We will also discuss implications for healthcare providers. PMID- 25114566 TI - The function of a medical director in healthcare institutions: a master or a servant. AB - The function of a medical director is presented along with features of efficiency and deficiencies from the perspective of healthcare system improvement. A MEDLINE/Pubmed research was performed using the terms "medical director" and "director", and 50 relevant articles were selected. Institutional healthcare quality is closely related to the medical director efficiency and deficiency, and a critical discussion of his or her function is presented along with a focus on the institutional policies, protocols, and procedures. The relationship between the medical director and the executive director is essential in order to implement a successful healthcare program, particularly in private facilities. Issues related to professionalism, fairness, medical records, quality of care, patient satisfaction, medical teaching, and malpractice are discussed from the perspective of institutional development and improvement strategies. In summary, the medical director must be a servant to the institutional constitution and to his or her job description; when his or her function is fully implemented, he or she may represent a local health governor or master, ensuring supervision and improvement of the institutional healthcare system. PMID- 25114567 TI - Use of GIS Mapping as a Public Health Tool-From Cholera to Cancer. AB - The field of medical geographic information systems (Medical GIS) has become extremely useful in understanding the bigger picture of public health. The discipline holds a substantial capacity to understand not only differences, but also similarities in population health all over the world. The main goal of marrying the disciplines of medical geography, public health and informatics is to understand how countless health issues impact populations, and the trends by which these populations are affected. From the 1990s to today, this practical approach has become a valued and progressive system in analyzing medical and epidemiological phenomena ranging from cholera to cancer. The instruments supporting this field include geographic information systems (GIS), disease surveillance, big data, and analytical approaches like the Geographical Analysis Machine (GAM), Dynamic Continuous Area Space Time Analysis (DYCAST), cellular automata, agent-based modeling, spatial statistics and self-organizing maps. The positive effects on disease mapping have proven to be tremendous as these instruments continue to have a great impact on the mission to improve worldwide health care. While traditional uses of GIS in public health are static and lacking real-time components, implementing a space-time animation in these instruments will be monumental as technology and data continue to grow. PMID- 25114569 TI - A Group Interview Regarding Disaster Preparedness for Food Assistance in a University that Offers a Training Course for Registered Dietitians. AB - Mass care feeding for disaster evacuees is an important component of public health preparedness. If universities that offer a training course for registered dietitians could provide food assistance to the evacuated people in their campus, it could contribute to maintain their health. Many universities are expected to become a base of support activities for people affected by disaster. This study aimed to reveal disaster preparedness in a university that offers a training course for registered dietitians, from the aspect of provision of mass care feeding. As Japan has 124 universities that offer such training courses, this case study could serve as a useful reference for them and contribute to the improvement of health of the affected people. A group interview was conducted in University A in 2012. The participants included two faculty members in the course, a vice president, a staff member, and a faculty member in charge of disaster preparedness and response. Stockpiled foods were limited to dry bread and pre-processed rice. No alternative heat sources were stored. It was concluded that to provide nutrients other than carbohydrate, hot meals should be served for the evacuees. Additionally, it would be difficult to provide meal service when the essential utilities such as gas and electricity are disrupted. PMID- 25114568 TI - Quality of care and quality of life: convergence or divergence? AB - The aim of this study was to explore the impact of quality of care (QoC) on patients' quality of life (QoL). In a cross-sectional study, two domains of QoC and the World Health Organization Quality of Life-Bref questionnaire were combined to collect data from 1,059 pre-discharge patients in four accredited hospitals (ACCHs) and four non-accredited hospitals (NACCHs) in Saudi Arabia. Health and well-being are often restricted to the characterization of sensory qualities in certain settings such as unrestricted access to healthcare, effective treatment, and social welfare. The patients admitted to tertiary health care facilities are generally able to present themselves with a holistic approach as to how they experience the impact of health policy. The statistical results indicated that patients reported a very limited correlation between QoC and QoL in both settings. The model established a positive, but ultimately weak and insignificant, association between QoC (access and effective treatment) and QoL (r = 0.349, P = 0.000; r = 0.161, P = 0.000, respectively). Even though the two settings are theoretically different in terms of being able to conceptualize, adopt, and implement QoC, the outcomes from both settings demonstrated insignificant relationships with QoL as the results were quite similar. Though modern medicine has substantially improved QoL around the world, this paper proposes that health accreditation has a very limited impact on improving QoL. This paper raises awareness of this topic with multiple healthcare professionals who are interested in correlating QoC and QoL. Hopefully, it will stimulate further research from other professional groups that have new and different perspectives. Addressing a transitional health care system that is in the process of endorsing accreditation, investigating the experience of tertiary cases, and analyzing deviated data may limit the generalization of this study. Global interest in applying public health policy underlines the impact of such process on patients' outcomes. As QoC accreditation does not automatically produce improved QoL outcomes, the proposed study encourages further investigation of the value of health accreditation on personal and social well-being. PMID- 25114570 TI - Anonymity: an impediment to performance in healthcare. AB - Many teaching hospitals employ a care team structure composed of a broad range of healthcare providers with different skill sets. Each member of this team has a distinct role and a different level of training ranging from attending physician to resident, intern, and medical student. Often times, these different roles lead to greater complexity and confusion for both patients and nursing staff. It has been demonstrated that patients have a great degree of difficulty in identifying members of their care team. This anonymity also exists between nursing staff and other care providers. In order to better understand the magnitude of anonymity within the teaching hospital, a ten-question survey was sent to nurses across three different departments. Results from this survey demonstrated that 71% of nurses are "Always" or "Often" able to identify which care team is responsible for their patients, while 79% of nurses reported that they either "Often" or "Sometimes" page a provider who is not currently caring for a given patient. Furthermore, 33% of nurses felt that they were either "Rarely" or "Never" able to recognize, by face and name, attending level providers. Residents were "Rarely" or "Never" recognized by face and name 37% of the time, and interns 42% of the time. Contacting the wrong provider repeatedly leads to de facto delays in medication, therapy, and diagnosis. Additionally, these unnecessary interruptions slow workflow for both nurses and members of the care team, making hospital care less efficient and safe overall. Technological systems should focus on reducing anonymity within the hospital in order to enhance healthcare delivery. PMID- 25114571 TI - Ambulatory and Hospital-based Quality Improvement Methods in Israel. AB - This review article compares ambulatory and hospital-based quality improvement methods in Israel. Data were collected from: reports of the National Program for Quality Indicators in community, the National Program for Quality Indicators in Hospitals, and from the Organization for Economic Cooperation and Development (OECD) Reviews of Health Care Quality. PMID- 25114572 TI - Prognostic significance of thymidylate synthase in postoperative non-small cell lung cancer patients. AB - The aim of the present study was to investigate the clinicopathologic/prognostic significance of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), and thymidine phosphorylase (TP) proteins in postoperative non-small cell lung cancer (NSCLC) patients. Microarray slides from a set of 178 NSCLC patients were used for the detection of TS, OPRT, and TP expression by immunohistochemistry. The correlation between clinicopathologic factors and protein expression of three proteins was analyzed. Ninety seven carcinomas (57.4%) were TS-positive, 90 carcinomas (53.9%) were OPRT-positive, and 102 carcinomas (69.4%) were TP-positive. Compared with the TS-positive patients, the overall survival (OS) was significantly lower in the TS-negative patients (hazard ratio [HR] =1.766, 95% confidence interval [CI] =1.212-2.573, P=0.003). Significant differences between TS-positive and TS-negative patients was also observed in the following stratified analyses: 1) adenocarcinoma subgroup (HR =2.079, 95% CI =1.235-3.500, P=0.006); 2) less than 60-year-old subgroup (HR =1.890, 95% CI =1.061-3.366, P=0.031); 3) stage II/III subgroup (HR =1.594, 95% CI =1.036-2.453, P=0.034); and 4) surgery plus adjuvant therapy subgroup (HR =1.976, 95% CI =1.226-3.185, P=0.005). However, the OS was not significantly correlated with OPRT or TP protein expression. This study demonstrates that the TS level in tumor tissues may be a useful marker to predict the postoperative OS in NSCLC patients. PMID- 25114574 TI - Paclitaxel- and/or cisplatin-induced ocular neurotoxicity: a case report and literature review. AB - Paclitaxel (PTX) and/or cisplatin (CDDP), as important cytotoxic anti-cancer agents, are widely used to treat various solid tumors. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity is also occasionally reported. A patient diagnosed with nasopharyngeal cancer suffering acute ocular neurotoxicity 10 days after paclitaxel and CDDP administration at the recommended dose is described in the present case report, and PTX- and/or CDDP-induced ocular neurotoxicity are summarized according to previous reports. Possible mechanisms and the potential diagnostic, therapeutic and predictive strategies of PTX- and/or CDDP-induced ocular neurotoxicity are reviewed, to help the oncologist to take the infrequent toxicity of cytotoxic drugs into account and improve patient safety during anti-cancer therapy. PMID- 25114573 TI - PD-1 as an emerging therapeutic target in renal cell carcinoma: current evidence. AB - Renal cell carcinoma (RCC) is the most common primary malignant tumor of the kidney in adults, representing approximately 4% of all adult cancers in the United States. Metastatic RCC is poorly responsive to conventional cytotoxic chemotherapies but can be sensitive to T-cell-directed immunotherapies such as interferon-alpha or interleukin-2. Despite recent progress in the application of antiangiogenic "targeted therapies" for metastatic RCC, high-dose interleukin-2 remains an appropriate first-line therapy for select patients and is associated with durable complete remissions in a small fraction of treated patients. Thus, advanced RCC provides a unique opportunity to investigate the requirements for effective antitumor immunotherapy. Accumulating evidence suggests that resistance mechanisms exploited by RCC and other tumor types may play a dominant role in limiting the effectiveness of tumor-reactive adaptive immune responses. Expression of the inhibitory coreceptor programmed cell death-1 (PD-1) on tumor infiltrating lymphocytes within RCC tumors, as well as the expression of the PD-1 ligand (PD-L1) on RCC tumor cells, are strong negative prognostic markers for disease-specific death in RCC patients. Monoclonal antibodies targeting either PD 1 or PD-L1 have now entered clinic trials and have demonstrated promising antitumor effects for refractory metastatic RCC. This review summarizes the results of published and reported studies of PD-1- and PD-L1-targeted therapies enrolling patients with advanced RCC, focusing on key safety, toxicity, and efficacy end points. Prospects for advanced phase clinical testing and novel therapy combinations with PD-1- and PD-L1-targeted agents are discussed. PMID- 25114576 TI - Prevalence of metabolic syndrome and its components based on a harmonious definition among adults in Morocco. AB - PURPOSE: Metabolic syndrome is a cluster of risk factors for diabetes and cardiovascular diseases that includes central obesity, hypertension, glucose intolerance, high triglyceride, and low high-density lipoprotein cholesterol. Its prevalence is rapidly increasing worldwide. This study aimed to estimate the prevalence of metabolic syndrome and associated risk factors in a representative sample of Morocco adults using the 2009 joint interim statement definition. PATIENTS AND METHODS: We analyzed data of 820 patients aged 19 years and older. For metabolic syndrome diagnosis, we used the criteria of the recently published joint interim statement (2009). RESULTS: The prevalence of metabolic syndrome is 35.73% among all adults, 18.56% among men, and 40.12% among women. Prevalence increased with age, peaking among those aged 50-59 years. The most common abnormality highlights abdominal obesity (49.15%). Also, half of patients have one or two risk factors for developing this syndrome. CONCLUSION: The prevalence of metabolic syndrome and associated risk factors is high among adults in Morocco, especially in women. The most prevalent component of metabolic syndrome in our population was abdominal obesity. PMID- 25114575 TI - Lapatinib for the treatment of breast cancer in the People's Republic of China. AB - Lapatinib is an oral, small-molecule, reversible inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor-2 (HER2) tyrosine kinases. In March 2007, the US Food and Drug Administration approved lapatinib for use in combination with capecitabine for the treatment of women with HER2-overexpressing, advanced or metastatic breast cancer. This review discusses the available information of lapatinib in Chinese breast cancer patients, focusing on its effectiveness and clinical application against advanced or metastatic breast cancer. In pivotal phase III trials, a combination of lapatinib and capecitabine significantly decreased the risk of disease progression compared to capecitabine alone in women with HER2-positive advanced or metastatic breast cancer. Other trials were used to evaluate lapatinib in combination with hormone therapy, in combination with trastuzumab, and as an adjunct to adjuvant therapy for early-stage disease. Preclinical data have revealed that lapatinib is active in trastuzumab-resistant cell lines as well as synergistic with trastuzumab. In clinical trials, lapatinib has not been associated with serious or symptomatic cardiotoxicity. Further, it can cross the blood-brain barrier and may therefore have a role in preventing cancer progression in the central nervous system. Thus, lapatinib warrants further evaluation in HER2-positive metastatic and early-stage breast cancer patients. PMID- 25114577 TI - Elevated body mass index as a risk factor for chronic kidney disease: current perspectives. AB - Chronic kidney disease (CKD) is defined by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative as the presence of reduced kidney function or kidney damage for a period of 3 months or greater. Obesity is considered a risk factor for CKD development, but its precise role in contributing to CKD and end stage kidney disease is not fully elucidated. In this narrative review, the objectives are to describe the pathogenesis of CKD in obesity, including the impact of altered adipokine secretion in obesity and CKD, and to provide an overview of the clinical studies assessing the risk of obesity and CKD development. PMID- 25114579 TI - Partners of patients with inflammatory bowel disease: how important is their support? AB - BACKGROUND: Chronic inflammatory bowel disease (IBD) causes significant distress for patients and their families. Data assessing the need of these patients for support and sharing with their partners are scarce. The aim of this study was to assess patients' views regarding sharing of information with their partners. METHODS: Ambulatory IBD patients treated at the Chaim Sheba Medical Center between January 2011 and January 2013 were asked to complete an anonymous questionnaire. Patients who had a stable partner and completed more than 95% of the questionnaire were included. RESULTS: Of 134 patients who agreed to complete the questionnaire, 101 met the inclusion criteria, 53 were men (mean age 45+/-15 years), and 50% had academic education. Only 42% of patients reported that their partner accompanied them to the doctor. However, 93% shared health problems with their partner, 64% would have liked their partner to receive more medical information, and 70% would like their partner to be more involved. The majority (88%) believed that more partner involvement could help them deal better with the disease, and 70% thought that support groups for partners should be established. No association was found between patients' demographic data and their answers. Patients who felt that partner involvement could help them to deal with the disease tended to share medical information with their partners and wanted them to be more involved in health care decision-making (P<0.001). CONCLUSION: Most IBD patients in our study wanted their partner to be more involved with their health problems, and believed that greater partner involvement could help them deal better with their disease. Therefore, more attention should be focused on gaining better cooperation from patients' families. PMID- 25114578 TI - Is adherence a relevant issue in the self-management education of diabetes? A mixed narrative review. AB - While therapeutic patient education is now recognized as essential for optimizing the control of chronic diseases and patient well-being, adherence to treatment and medical recommendations is still a matter of debate. In type 2 diabetes, the nonadherence to therapy, estimated at more than 40%, is perceived as a barrier for improving the prognosis despite recent therapeutic advances. Interventional studies have barely begun to demonstrate the effectiveness of technical and behavioral actions. The aim of this review is to question the concept of adherence in terms of therapeutic education based on quantitative and qualitative data. The research on therapeutic education has shown the effectiveness of structured actions in type 2 diabetes, but adherence is rarely an end point in randomized trials. A positive but inconsistent or moderate effect of education actions on adherence has been shown in heterogeneous studies of varying quality. Program types, outlines, theoretical bases, and curricula to set up for action effectiveness are still being discussed. Qualitative studies, including sociological studies, provide a useful and constructive focus on this perspective. Adherence is a soft and flexible tool available to the patient in his/her singular chronic disease trajectory, and as such, integrates into individual therapeutic strategies, including socio-cultural interactions, beyond the medical explanation of the disease and the patient. Four key elements for the development of structured therapeutic education are discussed: 1) the access to health literacy, 2) the contextualization of education activities, 3) the long term chronic dimension of self-management, and 4) the organizational aspects of health and care. Rather than focusing the objective on behavioral changes, structured therapeutic education actions should attempt to provide tools and resources aimed at helping individuals to manage their disease in their own context on a long-term basis, by developing health literacy and relational and organizational aspects of the health professionals and system. PMID- 25114580 TI - Improving the prognosis of nephropathic cystinosis. AB - Cystinosis is an autosomal recessive inherited lysosomal storage disease. It is characterized by generalized proximal tubular dysfunction known as renal Fanconi syndrome and causes end-stage renal disease by the age of about 10 years if left untreated. Extrarenal organs are also affected, including the thyroid gland, gonads, pancreas, liver, muscle, and brain. Treatment consists of administration of cysteamine, resulting in depletion of cystine that is trapped inside the lysosomes. Since cysteamine has a short half-life, it should be administered every 6 hours. Recently, a new delayed-release formulation was marketed, that should be administered every 12 hours. The first studies comparing both cysteamine formulations show comparable results regarding white blood cell cystine depletion (which serves as a measure for cystine accumulation in the body), while a slightly lower daily dose of cysteamine can be used. PMID- 25114581 TI - CYP19A1 single nucleotide polymorphism associations with CYP19A1, NFkappaB1, and IL6 gene expression in human normal colon and normal liver samples. AB - BACKGROUND: Estrogen is known to decrease the risk of colon cancer in postmenopausal women, and may exert its actions by decreasing interleukin-6 (IL6) production via stabilization of the transcription factor nuclear factor kappa light-chain-enhancer of activated B cells (NFkappaB). Estrogens are biosynthesized by CYP19A1 (aromatase), so it is possible that genetic variations in CYP19A1 influences the risk of colon cancer by altering expression of CYP19A1. Further, studies on gene-gene interactions suggest that single nucleotide polymorphisms in one gene may affect expression of other genes. The current study aims to explore the role of CYP19A1 single nucleotide polymorphisms on CYP19A1, NFkappaB1 and IL6 gene expression. METHODS: Phenotype-genotype associations, cross-associations between genes, and haplotype analyses were performed in both normal human colon (n=82) and liver (n=238) samples. RESULTS: CYP19A1 rs10459592, rs1961177, and rs6493497 were associated with CYP19A1 expression in colon samples (P=0.042, P=0.041, and P=0.013, respectively). CYP19A1 single nucleotide polymorphisms (rs12908960, rs730154, rs8025191, and rs17523880) were correlated with NFkappaB1 expression (P=0.047, P=0.04, P=0.05, and P=0.03, respectively), and CYP19A1 rs11856927, rs2470152, and rs2470144 (P=0.049, P=0.025, P=0.047, respectively) were associated with IL6 expression in the colon. While rs730154 and rs17523880 could not be analyzed in the liver samples, none of the other associations with the colon were replicated in the liver samples. Haplotype analysis revealed three separate haplotypes of the CYP19A1 single nucleotide polymorphism that were significantly associated with CYP19A1, NFkappaB1, and IL6 gene expression. CONCLUSION: CYP19A1 single nucleotide polymorphisms are associated not only with CYP19A1 expression but also with NFkappaB1 and IL6 expression. These data demonstrate the possible functional consequences of genetic variation within the CYP19A1 gene on other genes in a biologically plausible pathway. PMID- 25114583 TI - An infant with poor weight gain and hypochloremic metabolic alkalosis: a case report. AB - Bartter syndrome is an autosomal recessive disease manifested by a defect in chloride transport in the thick loop of Henle, with different genetic origins and molecular pathophysiology. Children with Bartter syndrome generally present in early infancy with persistent polyuria and associated dehydration, electrolyte imbalance, and failure to thrive. Although early diagnosis and appropriate treatment of Bartter syndrome may improve the outcome, some children will progress to renal failure. We report a case of an 8-week-old infant who was admitted for electrolyte imbalance and failure to thrive. Laboratory studies revealed hypochloremic metabolic alkalosis with severe hypokalemia. Health care providers should consider Bartter syndrome when excessive chloride losses appear to be renal in origin and the patient has normal blood pressure and high levels of serum renin and aldosterone. Treatments, including indomethacin, spironolactone, and aggressive fluid and electrolyte replacement, may prevent renal failure in children with Bartter syndrome. Molecular genetics studies are indicated to identify the primary genetic defect. PMID- 25114584 TI - An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. AB - PURPOSE: Studies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4-17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure. PATIENTS AND METHODS: This was a 53-week, multicenter, open-label trial of pregabalin (150-600 mg/day) in Japanese patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke. RESULTS: A total of 103 patients received pregabalin (post stroke =60; spinal cord injury =38; and multiple sclerosis =5). A majority of patients (87.4%) experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1%) or moderate (9.2%) in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS), and present pain intensity scores on the Short Form McGill Pain Questionnaire (SF-MPQ) and ten-item modified Brief Pain Inventory (mBPI-10) total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were -20.1 and -1.4, respectively. CONCLUSION: These findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in patients with chronic central neuropathic pain. PMID- 25114582 TI - MicroRNA binding site polymorphisms as biomarkers in cancer management and research. AB - MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression. They have been implicated in a broad range of biological processes, and miRNA-related genetic alterations probably underlie several human diseases. Single nucleotide polymorphisms of transcripts may modulate the posttranscriptional regulation of gene expression by miRNAs and explain interindividual variability in cancer risk and in chemotherapy response. On the basis of recent association studies published in the literature, the present review mainly summarizes the potential role of miRNAs as molecular biomarkers for disease susceptibility, diagnosis, prognosis, and drug-response prediction in tumors. Many clues suggest a role for polymorphisms within the 3' untranslated regions of KRAS rs61764370, SET8 rs16917496, and MDM4 rs4245739 as SNPs in miRNA binding sites highly promising in the biology of human cancer. However, more studies are needed to better characterize the composite spectrum of genetic determinants for future use of markers in risk prediction and clinical management of diseases, heading toward personalized medicine. PMID- 25114585 TI - Challenges in the development of future treatments for breast cancer stem cells. AB - The recurrence of tumors after years of disease-free survival has spurred interest in the concept that cancers may have a stem cell basis. Current speculation holds that as few as 0.1% of the tumor mass may be chemoresistant and radioresistant, harboring stem-like properties that drive tumor survival, development, and metastasis. There are intense investigations to characterize cancer stem cells on the basis of self-renewal and multi-lineage differentiation. Thus far, no successful targeted therapies have been developed and reached the clinic, but as these cells are isolated and characterized, insights may be unraveled. In this review, we discuss the controversy over the origins of the cancer stem cell hypothesis and the unforeseen factors that may facilitate breast cancer stem cell survival and metastasis. We discuss the role of tumor microenvironment, including carcinoma-associated fibroblasts, epigenetic factors, and the Th1/Th2 balance, in supporting breast cancer stem cells. In addition, we have incorporated ideas on the epithelial-to-mesenchymal transition in metastatic dissemination of epithelial malignancies. This area is relevant since breast cancer stem cells have been suggested to revert to a mesenchymal phenotype during the progression of cancer. Finally we discuss prospects of developing targeted therapy including novel treatment modalities such as oncolytic viral therapy, differentiation therapy, and nanotechnology. PMID- 25114588 TI - Role of trastuzumab emtansine in the treatment of HER2-positive breast cancer. AB - Trastuzumab is a monoclonal antibody that is used in the treatment of breast cancer. Trastuzumab targets the human epidermal growth factor receptor 2 (HER2) receptor on breast cancer cells that express this tyrosine kinase receptor. These cancers are referred to as HER2-positive breast cancer. The original studies of trastuzumab showed improved survival in metastatic breast cancer; however, resistance often develops. In the adjuvant setting, women often progress despite therapy that includes trastuzumab. Antibody-drug conjugates are a new class of powerful drugs designed to target high-dose chemotherapy directly to the cancer cells. Trastuzumab emtansine is one of these antibody-drug conjugates and was the first Food and Drug Administration approved drug for a solid tumor. Emtansine is a potent antimicrotubule agent. Trastuzumab is used to target this potent chemotherapy agent directly to the HER2-expressing cancer cells. This review article will summarize the evidence from the preclinical studies, summarize evidence from the clinical trials, discuss current clinical trials, discuss current approval of trastuzumab emtansine, and discuss future directions of research. PMID- 25114587 TI - Preserving fertility in patients undergoing treatment for breast cancer: current perspectives. AB - Invasive breast cancer (BC) is the most frequent cancer of young women. Considering the trend toward postponing childbearing until the later reproductive years, the number of childless women at diagnosis of BC will continue to increase. The American Society of Clinical Oncology and the American Society for Reproductive Medicine have recommended that the impact of cancer treatments on fertility should be addressed with all cancer patients of reproductive age and that options for fertility preservation, such as cryopreservation of embryos and oocytes, ovarian tissue, in vitro maturation of immature oocytes, and ovarian suppression with gonadotropin-releasing hormone analogs, should be discussed routinely. To optimally counsel patients on how to best weigh the risks and benefits of fertility preservation, both the health care provider and the patient must know about the options, their risks, and their likelihood of success. The aim of this review is to summarize current knowledge on fertility preservation options for young BC patients, surrogates of ovarian function, psychosocial aspects of infertility after cancer treatment, women's attitudes towards childbearing after cancer treatment, and health care providers' attitudes towards fertility preservation. PMID- 25114589 TI - Barrier protective use of skin care to prevent chemotherapy-induced cutaneous symptoms and to maintain quality of life in patients with breast cancer. AB - PURPOSE: Chemotherapy with anthracyclines, taxanes, or alkylating agents often causes cutaneous side effects. Nonspecific inhibition of the proliferative activity of keratinocytes has antidifferentiation effects that lead to defects in the barrier function and, thus, to dry, itchy, and irritable skin. These cutaneous symptoms reduce the quality of life of the patients considerably. Conditioning with topical application of niacinamide uses the cytoprotective and barrier stabilizing effect of vitamin B3. PATIENTS AND METHODS: A multicenter randomized crossover study investigated the influence of the test preparation on the quality of life compared to standard care for 73 patients with breast cancer undergoing adjuvant or neoadjuvant cytostatic therapy. Primary target parameter was the Dermatology Life Quality Index with its respective subscales after 6 weeks of a twice-daily application of the respective preparations. Additionally, specific symptoms such as pruritus, dryness, and irritability have been assessed using visual analog scales. RESULTS: Regarding the total score of the Dermatology Life Quality Index, no relevant differences could be observed. However, the results for the "symptoms and feelings" subscale show a significant advantage in favor of the test preparation. Significant superiority of the test preparation could also be observed in the secondary target parameters, the visual analog scales (P<0.05). CONCLUSION: The results show for the first time a significant superiority of prophylactic application of niacinamide for maintaining quality of life while undergoing cytostatic treatment. PMID- 25114586 TI - Candidate prognostic markers in breast cancer: focus on extracellular proteases and their inhibitors. AB - The extracellular matrix (ECM) is the complex network of proteins that surrounds cells in multicellular organisms. Due to its diverse nature and composition, the ECM has a multifaceted role in both normal tissue homeostasis and pathophysiology. It provides structural support, segregates tissues from one another, and regulates intercellular communication. Furthermore, the ECM sequesters a wide range of growth factors and cytokines that may be released upon specific and well-coordinated cues. Regulation of the ECM is performed by the extracellular proteases, which are tasked with cleaving and remodeling this intricate and diverse protein matrix. Accordingly, extracellular proteases are differentially expressed in various tissue types and in many diseases such as cancer. In fact, metastatic dissemination of tumor cells requires degradation of extracellular matrices by several families of proteases, including metalloproteinases and serine proteases, among others. Extracellular proteases are emerging as strong candidate cancer biomarkers for aiding and predicting patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in animal models of metastasis has shown impressive therapeutic effects. As such, many of these proteolytic inhibitors are currently in various phases of clinical investigation. In addition to direct approaches, aberrant expression of extracellular proteases in disease states may also facilitate the selective delivery of other therapeutic or imaging agents. Herein, we outline extracellular proteases that are either bona fide or probable prognostic markers in breast cancer. Furthermore, using existing patient data and multiple robust statistical analyses, we highlight several extracellular proteases and associated inhibitors (eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical biomarkers. With the recent advances in high-throughput technology and targeted therapies, the incorporation of extracellular protease status in breast cancer patient management may have a profound effect on improving outcomes in this deadly disease. PMID- 25114590 TI - The epidemiology of Sjogren's syndrome. AB - Sjogren's syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. It can present as an entity by itself, primary Sjogren's syndrome (pSS), or in addition to another autoimmune disease, secondary Sjogren's syndrome (sSS). pSS has a strong female propensity and is more prevalent in Caucasian women, with the mean age of onset usually in the 4th to 5th decade. Clinical presentation varies from mild symptoms, such as classic sicca symptoms of dry eyes and dry mouth, keratoconjunctivitis sicca, and xerostomia, to severe systemic symptoms, involving multiple organ systems. Furthermore, a range of autoantibodies can be present in Sjogren's syndrome (anti SSA/Ro and anti-SSB/La antibodies, rheumatoid factor, cryoglobulins, antinuclear antibodies), complicating the presentation. The heterogeneity of signs and symptoms has led to the development of multiple classification criteria. However, there is no accepted universal classification criterion for the diagnosis of Sjogren's syndrome. There are a limited number of studies that have been published on the epidemiology of Sjogren's syndrome, and the incidence and prevalence of the disease varies according to the classification criteria used. The data is further confounded by selection bias and misclassification bias, making it difficult for interpretation. The aim of this review is to understand the reported incidence and prevalence on pSS and sSS, the frequency of autoantibodies, and the risk of malignancy, which has been associated with pSS, taking into account the different classification criteria used. PMID- 25114591 TI - A comparison of the treatment effects of the Forsus Fatigue Resistance Device and the Twin Block appliance in patients with class II malocclusions. AB - OBJECTIVES: We evaluated the skeletal and dentoalveolar effects of the Forsus Fatigue Resistance Device (FRD) and the Twin Block appliance (TB) in comparison with nontreated controls in the treatment of patients with class II division 1 malocclusion. MATERIALS AND METHODS: THIS RETROSPECTIVE STUDY INCLUDED THREE GROUPS: TB (n=37; mean age, 11.2 years), FRD (n=30; mean age, 12.9 years), and controls (n=25; mean age, 12.6 years). Lateral cephalograms were evaluated at T1 (pretreatment) and at T2 (postappliance removal/equivalent time frame in controls). Cephalometric changes were evaluated using the Clark analysis, including 27 measurements. RESULTS: Sagittal correction of class II malocclusion appeared to be mainly achieved by dentoalveolar changes in the FRD group. The TB was able to induce both skeletal and dentoalveolar changes. A favorable influence on facial convexity was achieved by both groups. Significant upper incisor retroclination occurred with the TB (-12.42 degrees ), whereas only -4 degrees was observed in the FRD group. The lower incisors proclined more in the FRD group than the TB group. Incisor overjet reduction was 62% in the TB group versus 56% in the FRD group. Molar relation was corrected in both functional groups, resulting in a class I relation, although no change appeared in the control sample. CONCLUSION: Both appliances were effective in correcting the class II malocclusion. Both the FRD and the TB induced significant maxillary and mandibular dentoalveolar changes; skeletal changes were induced by TB but not FRD therapy. PMID- 25114592 TI - Arguments for and against HIV self-testing. AB - Approximately 60% of human immunodeficiency virus (HIV)-infected individuals are unaware of their infection, and stigma and discrimination continue to threaten acceptance of HIV testing services worldwide. Self-testing for HIV has garnered controversy for years and the debate reignited with the approval of a point-of care test for over-the-counter sale in the US in 2012. Here, we present arguments for and against HIV self-testing. The case in support of HIV self-testing contends that: the modality is highly acceptable, especially among the most at risk individuals; self-testing empowers users, thus helping to normalize testing; and mutual partner testing has the potential to increase awareness of risk and avert condomless sex between discordant partners. Arguments against HIV self testing include: cost limits access to those who need testing most; false negative results, especially during the window period, may lead to false reassurance and could promote sex between discordant partners at the time of highest infectivity; opportunities for counseling, linkage to care, and diagnosis of other sexually transmitted infections may be missed; and self-testing leads to potential for coercion between partners. Research is needed to better define the risks of self-testing, especially as performance of the assays improves, and to delineate the benefits of programs designed to improve access to self-test kits, because this testing modality has numerous potential advantages and drawbacks. PMID- 25114593 TI - Risk management of seasonal influenza during pregnancy: current perspectives. AB - Influenza poses unique risks to pregnant women, who are particularly susceptible to morbidity and mortality. Historically, pregnant women have been overrepresented among patients with severe illness and complications from influenza, and have been more likely to require hospitalization and intensive care unit admission. An increased risk of adverse outcomes is also present for fetuses/neonates born to women affected by influenza during pregnancy. These risks to mothers and babies have been observed during both nonpandemic and pandemic influenza seasons. During the H1N1 influenza pandemic of 2009-2010, pregnant women were more likely to be hospitalized or admitted to intensive care units, and were at higher risk of death compared to nonpregnant adults. Vaccination remains the most effective intervention to prevent severe illness, and antiviral medications are an important adjunct to ameliorate disease when it occurs. Unfortunately, despite national guidelines recommending universal vaccination for women who are pregnant during influenza season, actual vaccination rates do not achieve desired targets among pregnant women. Pregnant women are also sometimes reluctant to use antiviral medications during pregnancy. Some of the barriers to use of vaccines and medications during pregnancy are a lack of knowledge of recommendations and of safety data. By improving knowledge and understanding of influenza and vaccination recommendations, vaccine acceptance rates among pregnant women can be improved. Currently, the appropriate use of vaccination and antiviral medications is the best line of defense against influenza and its sequelae among pregnant women, and strategies to increase acceptance are crucial. This article will review the importance of influenza in pregnancy, and discuss vaccination and antiviral medications for pregnant women. PMID- 25114595 TI - Correlation between MRI results and intraoperative findings in patients with silicone breast implants. AB - BACKGROUND: Silicone gel breast implants may silently rupture without detection. This has been the main reason for magnetic resonance imaging (MRI) of the augmented or reconstructed breast. The aim of the present study was to investigate the accuracy of MRI for implant rupture. METHODS: Fifty consecutive patients with 85 silicone gel implants were included in the study. The mean age of the patients was 51 (range 21-72) years, with a mean duration of implantation of 3.8 (range 1-28) years. All patients underwent clinical examination and breast MRI. Intraoperative implant rupture was diagnosed by the operating surgeon. RESULTS: Nineteen of the 50 patients suffered from clinical symptoms. An implant rupture was diagnosed by MRI in 22 of 85 implants (26%). In seven of 17 removed implants (41%), the intraoperative diagnosis corresponded with the positive MRI result. However, only 57% of these patients were symptomatic. Ultrasound imaging of the harvested implants showed signs of interrupted inner layers of the implant despite integrity of the outer shell. By microsurgical separation of the different layers of the implant shell, we were able to reproduce this phenomenon and to produce signs of implant rupture on MRI. CONCLUSION: Our results show that rupture of only the inner layers of the implant shell with integrity of the outer shell leads to a misdiagnosis on MRI. Correlation with clinical symptoms and the specific wishes of the patient should guide the indication for implant removal. PMID- 25114596 TI - Idiopathic CD4+ lymphocytopenia in Hispanic male: case report and literature review. AB - INTRODUCTION: Idiopathic cluster of differentiation 4 (CD4+) T-cell lymphocytopenia (ICL) is a rare non human immunodeficiency virus (HIV)-related syndrome with unclear natural history and prognosis that was first reported and defined in 1992. ICL has been observed in patients after the onset of an opportunistic infection without known immunosuppression. CASE PRESENTATION: A 20 year-old Hispanic male patient without significant past medical history presented with progressive shortness of breath and cough for 3 weeks. Chest computed tomography showed bilateral cavitary lesions in the upper lung lobes. The HIV rapid screening test as well as the sputum acid-fast bacilli test were both positive. The patient was started on antituberculosis therapy. The CD4 count was noticed to be low. However, the HIV Western blot test was negative, and the HIV viral load was within normal limit. Further radiologic studies, hemato-oncologic, and autoimmune workups were normal. The patient was discharged on the treatment for tuberculosis. Follow-up after 8 weeks revealed a persistent low CD4+ count, and the repeated HIV tests were negative. CONCLUSION: The clinical features of ICL range from an asymptomatic condition to life-threatening complications that imitate the clinical course of HIV-infected patients. The differential diagnosis in adults comprises primarily HIV infection and other diseases or drug side effects. ICL is very rare and should be considered in the absence of any defined immunodeficiency or therapy associated with depressed levels of CD4+ T-cells. Early detection and recognition of the disease allow purposeful and systemic treatment approach and screening for the affected patients. PMID- 25114594 TI - Preserving fertility in young patients with endometrial cancer: current perspectives. AB - Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and affects predominantly postmenopausal women. It is estimated, however, that 15%-25% of women will be diagnosed before menopause. As more women choose to defer childbearing until later in life, the feasibility and safety of fertility-sparing EC management have been increasingly studied. Definitive treatment of total hysterectomy and bilateral salpingo-oophorectomy precludes future fertility and may thus be undesirable by women who wish to maintain their reproductive potential. However, the consideration of conservative management carries the oncologic risks of unstaged EC and the risk of missing a synchronous ovarian cancer. It is further complicated by the lack of consensus regarding the initial assessment, treatment, and surveillance. Conservative treatment with progestins has been shown to be a feasible and safe fertility-sparing approach for women with low grade, early stage EC with no myometrial invasion. The two most commonly adopted regimens are medroxyprogesterone acetate at 500-600 mg daily and megestrol acetate at 160 mg daily for a minimum of 6-9 months, with initial response rates commonly reported between 60% and 80% and recurrence rates between 25% and 40%. Photodynamic therapy and hysteroscopic EC excision have recently been reported as alternative approaches to progestin therapy alone. However, limited efficacy and safety data exist. Live birth rates after progestin therapy have typically been reported around 30%; however, when focusing only on those who do pursue fertility after successful treatment, the live birth rates were found to be higher than 60%. Assisted reproductive technology has been associated with a higher live birth rate compared with spontaneous conception, most likely reflecting the presence of infertility at baseline. Close follow-up is of paramount importance, and definitive treatment after completion of childbearing is advised. PMID- 25114597 TI - Differential renal adverse effects of ibuprofen and indomethacin in preterm infants: a review. AB - OBJECTIVE: The objective of this study was to evaluate the extent of renal adverse effects caused by ibuprofen or indomethacin in order to choose the safer drug to administer to preterm infants. METHODS: THE FOLLOWING THREE PARAMETERS OF RENAL FUNCTION WERE TAKEN INTO CONSIDERATION: 1) the urine output; 2) the serum creatinine concentration; and 3) the frequency of oliguria. The bibliographic search was performed using PubMed and Embase databases as search engines. RESULTS: Urine output ranged from 3.5+/-1.2 to 4.0+/-1.4 mL/kg/h after ibuprofen treatment, and from 2.8+/-1.1 to 3.6+/-1.4 mL/kg/h after indomethacin treatment. The values for ibuprofen are significantly (P<0.05) higher than those for indomethacin. The serum creatinine concentrations ranged from 0.98+/-0.24 to 1.48+/-0.2 mg/dL after ibuprofen treatment, and from 1.06+/-0.24 and 2.03+/-2.10 mg/dL after indomethacin treatment. The values for ibuprofen are significantly (P<0.05) lower than those for indomethacin. The frequency of oliguria ranged from 1.0% to 9.6% (ibuprofen) and from 14.8% to 40.0% (indomethacin), and was significantly lower following ibuprofen than indomethacin administration. In infants with body weight lower than 1,000 g, oliguria appeared in 5% (ibuprofen) and 40% (indomethacin; P=0.02). CONCLUSION: Indomethacin is associated with more severe renal adverse effects than ibuprofen. Ibuprofen is less nephrotoxic than indomethacin and should be used to treat patent ductus arteriosus in preterm infants. Immaturity increases the frequency of adverse effects of indomethacin. PMID- 25114598 TI - Evaluation of the angled Episcissors-60((r)) episiotomy scissors in spontaneous vaginal deliveries. AB - BACKGROUND: Obstetric anal sphincter injuries (OASIs) are the leading cause of anal incontinence in women. Episiotomies with a postdelivery suture angle of less than 30 degrees to the midline are more likely to injure the anal sphincter directly, while those with a suture angle of more than 60 degrees are associated with increased incidence of OASIs, as they do not relieve the pressure on the perineum. A safe zone of 40 degrees -60 degrees has been proposed. Recently, two new types of episiotomy scissors (Episcissors-60((r)) Straight version and angled version) were introduced to ensure a standardized cutting angle of 60 degrees to the midline. We audited our results with the angled Episcissors-60 in spontaneous vaginal deliveries. MATERIALS AND METHODS: Consecutive patients delivering in two private maternity hospitals in Thane, India undergoing clinically indicated episiotomies were included. Only patients delivering spontaneously were included. The scissors were introduced vaginally at crowning, and aligned to orient the guide limb vertically from the posterior fourchette to the anus. While a single cut was preferred, a stagger cut was needed for some women. Postdelivery angles were measured by placing a protractor transparency on the perineum after delivery and marking the angle with an indelible ink pen. Per rectal examination was performed prior to suturing to detect OASIs. RESULTS: A total of 25 women underwent clinically indicated episiotomies. Of these, 16 women were nulliparous, eight women were para 1, and one woman was a para 2. One woman had a vaginal breech delivery (para 2), and the rest were cephalic vertex deliveries. The average age was 27 (range 20-35) years. The median birth weight was 2,800 g (standard deviation 312 g, interquartile range 2,500-3,000 g). The median postdelivery suture angle of the episiotomy was 50 degrees (standard deviation 3.5 degrees , interquartile range 48 degrees -54 degrees , range 45 degrees -55 degrees ). No cases of OASI were detected in this series. CONCLUSION: The Episcissors-60 angled version demonstrated a postdelivery suture angle of 50 degrees in a cohort of Indian women undergoing spontaneous vaginal deliveries. PMID- 25114599 TI - Laser speckle contrast imaging for intraoperative assessment of liver microcirculation: a clinical pilot study. AB - BACKGROUND: Liver microcirculation can be affected by a wide variety of causes relevant to liver transplantation and resectional surgery. Intraoperative assessment of the microcirculation could possibly predict postoperative outcome. The present pilot study introduces laser speckle contrast imaging (LSCI) as a new clinical method for assessing liver microcirculation. METHODS: LSCI measurements of liver microcirculation were performed on ten patients undergoing liver resection. Measurements were made during apnea with and without liver blood inflow occlusion. Hepatic blood flow was assessed by subtracting zero inflow signal from the total signal. Zero inflow signal was obtained after hepatic artery and portal vein occlusion. Perfusion was expressed in laser speckle perfusion units, and intraindividual and interindividual variability in liver perfusion was investigated using the coefficient of variability. RESULTS: Hepatic microcirculation measurements were successfully made in all patients resulting in analyzable speckle contrast images. Mean hepatic blood flow was 410+/-36 laser speckle perfusion units. Zero inflow signal amounted to 40%+/-4% of the total signal. Intraindividual and interindividual coefficients of variability in liver perfusion were 25% and 28%, respectively. CONCLUSION: Under the conditions of this pilot study, LSCI allows rapid noncontact measurements of hepatic blood perfusion over wide areas. More studies are needed on methods of handling movement artifacts. PMID- 25114600 TI - Sealing vessels up to 7 mm in diameter solely with ultrasonic technology. AB - INTRODUCTION: Ultrasonic energy is a mainstay in the armamentarium of surgeons, providing multifunctionality, precision, and control when dissecting and sealing vessels up to 5 mm in diameter. Historically, the inability to seal vessels in the 5-7 mm range has been perceived as an inherent limitation of ultrasonic technology. The purpose of this study was to evaluate sealing of vessels up to 7 mm in diameter with an ultrasonic device that modulates energy delivery during the sealing period. METHODS: In ex vivo benchtop and in vivo acute and survival preclinical models, a new ultrasonic device, Harmonic ACE((r))+7 Shears (Harmonic 7), was compared with advanced bipolar devices in sealing vessels 1-7 mm in diameter with respect of burst pressure, seal reliability, and seal durability. Lateral thermal damage and transection time were also evaluated. RESULTS: Ex vivo tests of Harmonic 7 demonstrated significantly greater median burst pressures than an advanced bipolar device both for vessels <5 mm in diameter (1,078 mmHg and 836 mmHg, respectively, P=0.046) and for those in the range of 5-7 mm (1,419 mmHg and 591 mmHg, P<0.001). In vivo tests in porcine and caprine models demonstrated similar rates of hemostasis between Harmonic 7 and advanced bipolar devices, with high success rates at initial transection and seal durability of 100% after a 30-day survival period. CONCLUSION: Sealing 5-7 mm vessels is not a limitation of the type of energy used but of how energy is delivered to tissue. These studies document the ability of ultrasonic energy alone to reliably seal large vessels 5-7 mm in diameter, with significantly greater burst pressure observed in in vitro studies than those observed with an advanced bipolar technology when energy delivery is modulated during the sealing cycle. Furthermore, the seals created in 5-7 mm vessels are shown to be reliable and durable in in vivo preclinical studies. PMID- 25114603 TI - Transarterial chemoembolization using iodized oil for unresectable hepatocellular carcinoma: perspective from multistep hepatocarcinogenesis. AB - Transarterial chemoembolization (TACE) using iodized oil (Lipiodol((r))) (Lp TACE) as a carrier of chemotherapeutic agents has been routinely performed to control hepatocellular carcinomas (HCC) in Japan, and its use has yielded fairly beneficial therapeutic results. Lipiodol is thought to pass through the tumor sinusoids of HCC and reach the outflow drainage areas, namely, the portal venous side of the tumor. By doing this, Lipiodol blocks not only the tumor's arterial inflow but also its portal venous outflow, providing sufficient ischemic effects. It is known that the inflow blood system, tumor sinusoids, and outflow blood system change drastically during the process of multistep hepatocarcinogenesis; thus, it is reasonable to postulate that the distribution of Lipiodol and the subsequent therapeutic effect of Lp-TACE may also change during that process. Arterial inflow to HCC is highest for moderately differentiated HCC (mHCC) and is relatively low in well or poorly differentiated HCC (wHCC and pHCC, respectively). It has been suggested that the metabolic state of wHCC and mHCC is aerobic, while that of pHCC is anaerobic. The tumor sinusoids in wHCC and mHCC are small in size and large in number, while those in pHCC are large in size and small in number. This finding results in a greater chance of tumor cell exposure to chemotherapeutic agents in the former and a lesser chance in the latter. The outflow tract, namely, the drainage system via the residual portal venous branches within the pseudocapsule, is more complete in mHCC and pHCC and less so in wHCC. Considering all of these components of HCC of different histological grades, Lp-TACE should have the greatest effect on mHCC and a relatively low effect on wHCC and pHCC. To achieve consistently high therapeutic results, it is important to consider these components, which affect the sensitivity of HCC to Lp TACE, to maximize both the chemotherapeutic and ischemic effects of this therapy. PMID- 25114602 TI - Ending hepatitis C in the United States: the role of screening. AB - The US faces at least two distinct epidemics of hepatitis C virus infection (HCV), and due largely to revised screening recommendations and novel therapeutic agents, corresponding opportunities. As only 49%-75% of HCV-infected persons in the US are aware of their infection, any chance of addressing HCV in the US is dependent upon screening to identify undiagnosed infections. Most HCV in the US consists of longstanding infections among persons born during 1945-1965 who are suffering escalating rates of liver-related morbidity and mortality. Mathematical modeling supports aggressive action to reach and treat these persons to minimize the subsequent burden of advanced liver disease on patients and the health care system. Incident infection is primarily among persons who inject drugs, less than 10% of whom have been treated for HCV. Expanded screening and treatment of active persons who inject drugs raises the prospect of utilizing "treatment as prevention" to stem the tide of incident HCV infections in this population. HIV positive men who have sex with men (MSM) represent a population at risk for sexually transmitted HCV who may also benefit from adjusted screening guidelines to identify both acute and chronic infections. Prisoners also represent a critical population for aggressive screening and treatment. Finally, the two stage testing algorithm for HCV diagnosis is problematic and difficult for patients and providers to navigate. While emerging therapeutics raise the prospect of reducing HCV-related morbidity and mortality, as well as eliminating new infections, major barriers remain with regard to identifying infections, improving access to treatment, and ensuring payer coverage of costly new therapeutic regimens. PMID- 25114601 TI - Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents. AB - Hepatitis C virus (HCV) has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world's population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL28B) gene and natural clearance of HCV infection or after PEGylated interferon alpha and ribavirin treatment with and without direct antiviral agents. This paper synthesizes the recent advances in the pharmacogenetics of HCV infection in the era of triple therapies. PMID- 25114604 TI - Transtendon rotator-cuff repair of partial-thickness articular surface tears can lead to medial rotator-cuff failure. AB - PURPOSE: The purpose of this study was to evaluate clinical and anatomic outcomes of patients following transtendon rotator-cuff repair of partial articular supraspinatus tendon avulsion (PASTA) lesions. PATIENTS AND METHODS: Patients in the senior author's practice who had isolated PASTA lesions treated by transtendon rotator-cuff repair were included (n=8) and retrospectively reviewed. All patients were evaluated preoperatively and at a mean of 21.2 months (+/-9.7 months) postoperatively using standardized clinical evaluation (physical exam, American Shoulder and Elbow Surgeons, and Simple Shoulder Test). All patients underwent postoperative imaging with a magnetic resonance imaging arthrogram. RESULTS: There was a significant improvement in American Shoulder and Elbow Surgeons (42.7+/-17.5 to 86.9+/-25.2) and Simple Shoulder Test (4.6+/-3.2 to 10.1+/-3.8) scores from pre- to postoperative, respectively. Postoperative imaging demonstrated full-thickness medial cuff tearing in seven patients, and one patient with a persistent partial articular surface defect. CONCLUSION: Transtendon repair of PASTA lesions may lead to improvements in clinical outcome. However, postoperative imaging demonstrated a high incidence of full-thickness rotator-cuff defects following repair. PMID- 25114605 TI - Sex difference in top performers from Ironman to double deca iron ultra triathlon. AB - This study investigated changes in performance and sex difference in top performers for ultra-triathlon races held between 1978 and 2013 from Ironman (3.8 km swim, 180 km cycle, and 42 km run) to double deca iron ultra-triathlon distance (76 km swim, 3,600 km cycle, and 844 km run). The fastest men ever were faster than the fastest women ever for split and overall race times, with the exception of the swimming split in the quintuple iron ultra-triathlon (19 km swim, 900 km cycle, and 210.1 km run). Correlation analyses showed an increase in sex difference with increasing length of race distance for swimming (r (2)=0.67, P=0.023), running (r (2)=0.77, P=0.009), and overall race time (r (2)=0.77, P=0.0087), but not for cycling (r (2)=0.26, P=0.23). For the annual top performers, split and overall race times decreased across years nonlinearly in female and male Ironman triathletes. For longer distances, cycling split times decreased linearly in male triple iron ultra-triathletes, and running split times decreased linearly in male double iron ultra-triathletes but increased linearly in female triple and quintuple iron ultra-triathletes. Overall race times increased nonlinearly in female triple and male quintuple iron ultra-triathletes. The sex difference decreased nonlinearly in swimming, running, and overall race time in Ironman triathletes but increased linearly in cycling and running and nonlinearly in overall race time in triple iron ultra-triathletes. These findings suggest that women reduced the sex difference nonlinearly in shorter ultra triathlon distances (ie, Ironman), but for longer distances than the Ironman, the sex difference increased or remained unchanged across years. It seems very unlikely that female top performers will ever outrun male top performers in ultratriathlons. The nonlinear change in speed and sex difference in Ironman triathlon suggests that female and male Ironman triathletes have reached their limits in performance. PMID- 25114606 TI - Weight status and the perception of body image in men. AB - Understanding the role of body size in relation to the accuracy of body image perception in men is an important topic because of the implications for avoiding and treating obesity, and it may serve as a potential diagnostic criterion for eating disorders. The early research on this topic produced mixed findings. About one-half of the early studies showed that obese men overestimated their body size, with the remaining half providing accurate estimates. Later, improvements in research technology and methodology provided a clearer indication of the role of weight status in body image perception. Research in our laboratory has also produced diverse findings, including that obese subjects sometimes overestimate their body size. However, when examining our findings across several studies, obese subjects had about the same level of accuracy in estimating their body size as normal-weight subjects. Studies in our laboratory also permitted the separation of sensory and nonsensory factors in body image perception. In all but one instance, no differences were found overall between the ability of obese and normal-weight subjects to detect overall changes in body size. Importantly, however, obese subjects are better at detecting changes in their body size when the image is distorted to be too thin as compared to too wide. Both obese and normal-weight men require about a 3%-7% change in the width of their body size in order to detect the change reliably. Correlations between a range of body mass index values and body size estimation accuracy indicated no relationship between these variables. Numerous studies in other laboratories asked men to place their body size into discrete categorizes, ranging from thin to obese. Researchers found that overweight and obese men underestimate their weight status, and that men are less accurate in their categorizations than are women. Cultural influences have been found to be important, with body size underestimations occurring in cultures where a larger body is found to be desirable. Methodological issues are reviewed with recommendations for future studies. PMID- 25114609 TI - Examining the relationship between ethnicity and the use of drug-related services: an ethnographic study of Nepali drug users in Hong Kong. AB - A recent survey has shown that Nepali drug users in Hong Kong tend to have a low rate of usage of day-care and residential rehabilitation services, but a high rate of usage of methadone services. Little is known about the reasons behind such a pattern. Therefore, in this study, a 12-month ethnographic examination has been implemented in three sites, including a day-care center, residential rehabilitation center, and methadone clinic, to explore the experiences of 20 Nepali drug users in their use of drug-related services in Hong Kong and to examine the relationship between ethnicity and the use of drug-related services. The result shows that the reason for this pattern of service use is related to the approach of the services and the cultural perception of the service providers about the service users. The day-care and residential rehabilitation services emphasize an integrated approach, but the staff tend to overlook the heterogeneity of their clients, for example, the differences in caste and sex, and fail to provide suitable services to them, whereas the methadone service follows a biomedical model, which seldom addresses the social characteristics of the service users, which in turn minimizes the opportunity for misunderstandings between the staff and the clients. This research shows that ethnicity is a significant factor in drug treatment and that culture-specific treatment that takes into consideration the treatment approach and the heterogeneity of the clients is strongly needed. PMID- 25114610 TI - Program- and service-level costs of seven screening, brief intervention, and referral to treatment programs. AB - This paper examines the costs of delivering screening, brief intervention, and referral to treatment (SBIRT) services within the first seven demonstration programs funded by the US Substance Abuse and Mental Health Services Administration. Service-level costs were estimated and compared across implementation model (contracted specialist, inhouse specialist, inhouse generalist) and service delivery setting (emergency department, hospital inpatient, outpatient). Program-level costs were estimated and compared across grantee recipient programs. Service-level data were collected through timed observations of SBIRT service delivery. Program-level data were collected during key informant interviews using structured cost interview guides. At the service level, support activities that occur before or after engaging the patient comprise a considerable portion of the cost of delivering SBIRT services, especially short duration services. At the program level, average costs decreased as more patients were screened. Comparing across program and service levels, the average annual operating costs calculated at the program level often exceeded the cost of actual service delivery. Provider time spent in support of service provision may comprise a large share of the costs in some cases because of potentially substantial fixed and quasifixed costs associated with program operation. The cost structure of screening, brief intervention, and referral to treatment is complex and discontinuous of patient flow, causing annual operating costs to exceed the costs of actual service provision for some settings and implementation models. PMID- 25114607 TI - The role of the monoamine oxidase A gene in moderating the response to adversity and associated antisocial behavior: a review. AB - Hereditary factors are increasingly attracting the interest of behavioral scientists and practitioners. Our aim in the present article is to introduce some state-of-the-art topics in behavioral genetics, as well as selected findings in the field, in order to illustrate how genetic makeup can modulate the impact of environmental factors. We focus on the most-studied polymorphism to date for antisocial responses to adversity: the monoamine oxidase A gene. Advances, caveats, and promises of current research are reviewed. We also discuss implications for the use of genetic information in applied settings. PMID- 25114611 TI - Expanding the National Drug Abuse Treatment Clinical Trials Network to address the management of substance use disorders in general medical settings. AB - The Patient Protection and Affordable Care Act (2010) and the Mental Health Parity and Addiction Equity Act (2008) expand substance use disorder (SUD) care services in the USA into general medical settings. Care offered in these settings will engage substance-using patients in an integrated and patient-centered environment that addresses physical and mental health comorbidities and follows a chronic care model. This expansion of SUD services presents a great need for evidence-based practices useful in general medical settings, and reveals several research gaps to be addressed. The National Drug Abuse Treatment Clinical Trials Network of the National Institute on Drug Abuse can serve an important role in this endeavor. High-priority research gaps are highlighted in this commentary. A discussion follows on how the National Drug Abuse Treatment Clinical Trials Network can transform to address changing patterns in SUD care to efficiently generate evidence to guide SUD treatment practice within the context of recent US health care legislation. PMID- 25114613 TI - Back from the brink - a note of thanks. PMID- 25114612 TI - Patient registries for substance use disorders. AB - This commentary discusses the need for developing patient registries of substance use disorders (SUD) in general medical settings. A patient registry is a tool that documents the natural history of target diseases. Clinicians and researchers use registries to monitor patient comorbidities, care procedures and processes, and treatment effectiveness for the purpose of improving care quality. Enactments of the Affordable Care Act 2010 and the Mental Health Parity and Addiction Equity Act 2008 open opportunities for many substance users to receive treatment services in general medical settings. An increased number of patients with a wide spectrum of SUD will initially receive services with a chronic disease management approach in primary care. The establishment of computer-based SUD patient registries can be assisted by wide adoption of electronic health record systems. The linkage of SUD patient registries with electronic health record systems can facilitate the advancement of SUD treatment research efforts and improve patient care. PMID- 25114614 TI - Pediatric facial transplantation: Ethical considerations. AB - Facial transplantation is becoming increasingly accepted as a method of reconstructing otherwise unreconstructable adult faces. As this modality is made more available, we must turn our attention to pediatric patients who may benefit from facial transplantation. In the current article, the authors present and briefly examine the most pressing ethical challenges posed by the possibility of performing facial transplantation on pediatric patients. Furthermore, they issue a call for a policy statement on pediatric facial transplantation. The present article may serve as a first step in that direction, highlighting ethical issues that would need to be considered in the creation of such a statement. PMID- 25114615 TI - Tracking the aesthetic outcomes of prosthetic breast reconstructions that have complications. AB - BACKGROUND: Aesthetic results following breast reconstruction have been shown to be a major contributor to patient satisfaction. While many presume that complications after reconstruction impact final aesthetic results, little data exist to substantiate this putative relationship. OBJECTIVE: To track and evaluate aesthetic outcomes following implant reconstructions with complications. METHODS: A chart review was conducted on a series of consecutive expander-implant breast reconstructions performed by the senior author between 2004 and 2012. Included patients completed their prosthetic reconstruction or converted to autologous methods and had a minimum follow-up period of 130 days. Four blinded members of the division of plastic surgery independently rated postoperative anterior photographs of patients' breasts using a validated scoring scale with respect to five distinct aesthetic domains: breast mound volume, contour, placement, scarring and inframammary fold. RESULTS: Of the 172 patients who met the inclusion criteria, 36 experienced a complication. The tissue expander in one half of these patients was salvaged and the remaining patients converted to autologous reconstruction. The average aesthetic scores for each domain did not differ significantly between patients who experienced a complication and retained their expander and those who did not experience a complication. Patients who converted to autologous tissue reconstruction after experiencing a complication had the highest aesthetic scores. DISCUSSION: The ability to obtain aesthetic results following a complication that were not statistically different from results in those without complications may reflect the surgeon's refined attempt to salvage the initial implant reconstruction; in other circumstances, the improved cosmesis was achieved through conversion to an autologous tissue-based method. CONCLUSION: The present study quantitatively assessed the impact of complications on aesthetic outcomes following implant breast reconstruction. Continuance of prosthetic reconstruction and conversion to autologous reconstruction serve as viable options to obtain adequate aesthetic scores following a complication. Information gained from the present analysis will help manage patient expectations. PMID- 25114616 TI - Are online learning modules an effective way to deliver hand trauma management continuing medical education to emergency physicians? AB - BACKGROUND: The enormity of modern medical knowledge and the rapidity of change have created increased need for ongoing or continuing medical education (CME) for physicians. Online CME is attractive for its availability at any time and any place, low cost and potentially increased effectiveness compared with traditional face-to-face delivery. OBJECTIVE: To determine whether online CME modules are an effective method for delivering plastic surgery CME to primary care physicians. METHODS: A needs assessment survey was conducted among all emergency and family physicians in Nova Scotia. Results indicated that this type of program was appealing, and that hand trauma related topics were most desired for CME. 7 Lesson Builder (SoftChalk LLC, www.softchalk.com) was used to construct a multimedia e-learning module that was distributed along with a pretest, post-test and feedback questionnaire. Quantitative (pre- and post-test scores) and qualitative (feedback responses) data were analyzed. RESULTS: The 32 participants who completed the study indicated that it was a positive and enjoyable experience, and that there was a need for more resources like this. Compared with pretest scores, there was a significant gain in knowledge following completion of the module (P=0.001). CONCLUSION: The present study demonstrated that an e learning format is attractive for this population and effective in increasing knowledge. This positive outcome will lead to development of additional modules. PMID- 25114617 TI - Early outcomes of arthroplasty of the first carpometacarpal joint using pyrocarbon spherical implants. AB - The first carpometacarpal joint (CMC) is the most common hand joint to develop osteoarthritis. A survey found that many hand surgeons have revisited implant arthroplasty because it preserves critical structures. However, there is currently no implant with an ideal design and material composition. The present study was the first to use and evaluate early outcomes of pyrocarbon spherical implants for arthroplasty of the first CMC in patients with Eaton-Littler stage II and III osteoarthritis. A single surgeon performed 24 arthroplasties (23 patients [20 women, three men] with a mean age of 56 years [range 46 to 75 years]) of the first CMC (nine right hands and 15 left hands) using pyrocarbon spherical implants from May 2010 to April 2013. All patients failed conservative management. At a mean (+/- SD) of 18.5+/-11.16 months postoperatively (range 4.3 to 38.9 months), the mean Kapandji score was 8.8 of 10 (range 7 to 10), the average pre- and postoperative values on the visual pain scale were 8.96+/-0.64 of 10 (range 8 to 10) and 1.13+/-1.22 of 10 (range 0 to 4), respectively. All patients were either very satisfied (score = 5) or satisfied (score = 4) with the procedure, with a mean satisfaction score of 4.76+/-0.44 of 5.00 (range 4 to 5). The mean postoperative Disabilities of the Arm, Shoulder and Hand (DASH) score was 11.79+/-14.29 (range 0 to 49.17). The most recent radiographic evaluations confirmed that all implants were stable with no erosion of nearby cancellous bone. There were no implant subluxations, dislocations or revisions. Early outcomes show promising results and support continued use of this implant for arthroplasty. However, longer-term follow-up will be needed to confirm these results. PMID- 25114618 TI - Testing the effects of long-acting steroids in edema and ecchymosis after closed rhinoplasty. AB - BACKGROUND: Steroids have proven to be of some benefit in rhinoplasty edema and ecchymosis when administered at a high and repeated dose. OBJECTIVE: To evaluate the effects of single-dose, long-acting intramuscular steroids on postoperative edema and ecchymosis after closed rhinoplasty with osteotomies compared with placebo. METHODS: A randomized, double-blinded, placebo-controlled trial was performed. Fifty-four patients were randomly assigned to two groups: 28 received a single dose of long-acting dexamethasone (mean [+/- SD] dose 16+/-4 mg) immediately before anesthetic induction; the remaining 26 received an intramuscular injection of saline solution. The same surgeon performed all surgeries, with patients under general anesthesia. Acetaminophen was the only analgesic used to control postoperative pain. High-resolution digital photographs were taken on postoperative days 1, 3, 7 and 14. Scoring was performed separately for eyelid swelling and ecchymosis by an independent observer using a graded scale (0 to 5) for edema and a scoring system (0 to 13) for ecchymosis. RESULTS: No statistically significant differences in terms of age, sex or amount of bleeding during surgery were found between the two groups. No statistically significant difference was observed in the decrease of both ecchymosis and edema between placebo and high-dose, long-acting dexamethasone. A statistically significant difference in operation time was found, favouring the steroid group. No severe complications were observed due to steroid use. DISCUSSION: Osteotomies are basically a form of (controlled) trauma, with considerable disruption of the abundant blood vessels in this facial region and, therefore, are associated with with undesirable effects. A recent meta-analysis failed to show benefits of the use of steroids after postoperative day 3. Only a trend toward reduction in edema and ecchymosis with the use of long-acting steroids compared with placebo was demonstrated in the present study. CONCLUSION: There was no benefit in administering single-dose, long-acting steroids in patients undergoing closed rhinoplasty with osteotomies. PMID- 25114619 TI - The unfunded costs incurred by patients accessing plastic surgical care in Northern Saskatchewan. AB - The Canadian health care system was designed to ensure that all Canadian citizens would receive equal access to health care. However, in rural areas of Canada, patients are required to travel long distances and pay significant out-of-pocket expenses to access health care. The present study attempted to quantify the added out-of-pocket costs that rural Saskatchewan residents must pay to receive plastic surgical specialist care compared with urban residents of Saskatoon. A cost analysis was performed to generate a numerical value that would represent a minimum cost for patients travelling from three different locations within the province. The cost analysis performed in the present study approximated that the unfunded costs for common plastic surgical procedures are, at a minimum, 30 times greater for rural patients in La Ronge compared with their urban counterparts in Saskatoon. The fundamental principle of the Canadian health care system is equal access to necessary health care for all Canadians. Despite this, inequalities persist. The present cost-analysis study demonstrated that the unfunded (out-of pocket) expenses for rural Saskatchewan patients seeking plastic surgical treatment is significantly higher than for their urban counterparts. These unfunded costs represent a significant barrier to health care access in Canada and serve to propagate inequalities in the nation's heath care system. PMID- 25114620 TI - Meta-analysis of antibiotic prophylaxis in breast reduction surgery. AB - BACKGROUND: Breast reduction surgery is a very common procedure; however, there is still no consensus as to whether antibiotics should be used perioperatively. OBJECTIVE: To review the world literature and perform a meta-analysis of studies comparing wound infection rates with antibiotic use in breast reduction surgery. METHODS: A literature search was performed using the MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Database of Clinical Trials, Embase and CINAHL databases. Subject headings and relevant subheadings for "Breast", "Breast Reduction", "Reduction Mammaplasty", "Mammaplasty" were combined with "Antibiotics" and "Antibacterial Agents". The list of titles was assessed by the study's authors and abstracts were reviewed. All relevant articles were then independently reviewed by the two primary authors, and Jadad scoring was used to assess the quality of the included articles. RESULTS: From the original search, three randomized controlled trials were included in the meta-analysis of preoperative antibiotics. The meta-analysis revealed a 75% reduction in wound infections with preoperative antibiotics (OR 0.25 [95% CI 0.09 to 0.72]). Because only one randomized controlled trial analyzed postoperative antibiotics, no meta analysis could be performed. CONCLUSIONS: Preoperative antibiotics should routinely be used before breast reduction surgery. The use of postoperative antibiotics remains controversial. Additional randomized studies investigating postoperative antibiotics are needed. PMID- 25114621 TI - A review of hydrofluoric acid burn management. AB - Hydrofluoric acid (HF) causes a unique chemical burn. Much of the current treatment knowledge of HF burns is derived from case reports, small case series, animal studies and anecdotal evidence. The management can be challenging because clinical presentation and severity of these burns vary widely. Plastic surgeons managing burn patients must have a basic understanding of the pathophysiology, the range of severity in presentation and the current treatment options available for HF burns. The present article reviews the current understanding of the pathophysiology and systemic effects associated with severe HF burns. Furthermore, it distinguishes between minor and life-threatening HF burns and describes several of the basic techniques that are available to treat patients with HF burns. PMID- 25114622 TI - Inpatient silver sulphadiazine versus outpatient nanocrystalline silver models of care for pediatric scald burns: A value analysis. AB - BACKGROUND/OBJECTIVE: Scalds represent the most frequent pediatric burn injury. Inpatient nonsurgical wound management of small or medium-size burns (<20% total body surface area) represents a significant proportion of the cost of care, with nanocrystalline silver (NCS) and silver sulphadiazine (SSD) among the most commonly used dressings. Although several articles have described healing outcomes using these dressings, there are few concurrent economic analyses. To analyze overall health care value (outcomes/cost) in burns not requiring surgery, the authors compared management of scald burns with NCS versus SSD from both a quality perspective and using bottom-up microcosting to determine which dressing option optimizes health care value. METHODS: A value analysis was performed. Published studies investigating NCS and/or SSD in the treatment of pediatric burns over the past 25 years were analyzed. Healing time, hospital duration and frequency of dressings were chosen as quality metrics. A bottom-up microcosting analysis was performed to estimate costs associated with the two dressing options. RESULTS: Over the 25-year period, 356 studies investigated the use of SSD in burns, while 55 studies evaluated the use of NCS. Mean age and burn size were equivalent. Mean time to healing was 14.9 days for NCS and 17.2 days for SSD. The mean duration of hospital stay was 14.9 days for SSD and 5.9 days for NCS. Dressings were performed twice per week for NCS, and once or twice per day for SSD. The mean total cost per patient to the health care system was estimated to be $61,140 for SSD and $17,220 for NCS. CONCLUSION: Published outcomes of healing time are equivalent or slightly better using NCS over SSD for pediatric scalds. The financial model illustrated a potential significant cost saving with NCS, primarily as a result of an outpatient model of care. Overall health care value is optimized using NCS for pediatric scalds. PMID- 25114625 TI - Oral exam. PMID- 25114626 TI - The instruments of debt. PMID- 25114624 TI - Is routine pathological evaluation of tissue from gynecomastia necessary? A 15 year retrospective pathological and literature review. AB - OBJECTIVE: To reconsider the routine plastic surgical practice of requesting histopathological evaluation of tissue from gynecomastia. METHOD: The present study was a retrospective histopathological review (15-year period [1996 to 2012]) involving gynecomastia tissue samples received at the pathology laboratory in the Saskatoon Health Region (Saskatchewan). The Laboratory Information System (LIS) identified all specimens using the key search words "gynecomastia", "gynaecomastia", "gynecomazia" and "gynaecomazia". A literature review to identify all cases of incidentally discovered malignancies in gynecomastia tissue specimens over a 15-year period (1996 to present) was undertaken. RESULTS: The 15 year LIS search detected a total of 452 patients that included two cases of pseudogynecomastia (0.4%). Patients' age ranged from five to 92 years and 43% of the cases were bilateral (28% left sided, 29% right sided). The weight of the specimens received ranged from 0.2 g to 1147.2 g. All cases showed no significant histopathological concerns. The number of tissue blocks sampled ranged from one to 42, averaging four blocks/case (approximately $105/case), resulting in a cost of approximately $3,200/year, with a 15-year expenditure of approximately $48,000. The literature review identified a total of 15 incidental findings: ductal carcinoma in situ (12 cases), atypical ductal hyperplasia (two cases) and infiltrating ductal carcinoma (one case). CONCLUSIONS: In the context of evidence based literature, and because no significant pathological findings were detected in this particular cohort of 452 cases with 2178 slides, the authors believe it is time to re-evaluate whether routine histopathological examination of tissue from gynecomastia remains necessary. The current climate of health care budget fiscal restraints warrants reassessment of the current policies and practices of sending tissue samples of gynecomastia incurring negative productivity costs on routine histopathological examination. PMID- 25114623 TI - Breast reconstruction following prophylactic or therapeutic mastectomy for breast cancer: Recommendations from an evidence-based provincial guideline. AB - The side effects of mastectomy can be significant. Breast reconstruction may alleviate some distress; however, there are currently no provincial recommendations regarding the integration of reconstruction with breast cancer therapy. The purpose of the present article is to provide evidence-based strategies for the management of patients who are candidates for reconstruction. A systematic review of meta-analyses, guidelines, clinical trials and comparative studies published between 1980 and 2013 was conducted using the PubMed and EMBASE databases. Reference lists of publications were manually searched for additional literature. The National Guidelines Clearinghouse and SAGE directory, as well as guideline developers' websites, were also searched. Recommendations were developed based on the available evidence. Reconstruction consultation should be made available for patients undergoing mastectomy. Tumour characteristics, cancer therapy, patient comorbidities, body habitus and smoking history may affect reconstruction outcomes. Although immediate reconstruction should be considered whenever possible, delayed reconstruction is acceptable when immediate is not available or appropriate. The integration of reconstruction and postmastectomy radiotherapy should be addressed in a multidisciplinary setting. The decision as to which type of procedure to perform (autologous or alloplastic with or without acellular dermal matrices) should be left to the discretion of the surgeons and the patient after providing counselling. Skin-sparing mastectomy is safe and appropriate. Nipple-sparing is generally not recommended for patients with malignancy, but could be considered for carefully selected patients. Immediate reconstruction requires resources to coordinate operating room time between the general and plastic surgeons, to provide supplies including acellular dermal matrices, and to develop the infrastructure needed to facilitate multidisciplinary discussions. PMID- 25114627 TI - Development of positive antinuclear antibodies and rheumatoid factor in systemic juvenile idiopathic arthritis points toward an autoimmune phenotype later in the disease course. AB - BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is commonly considered an autoinflammatory disease. However, sJIA patients may develop aggressive arthritis without systemic inflammation later in the disease, resembling an autoimmune phenotype similar to other subtypes of JIA. The objective of this study was to determine whether antinuclear antibodies (ANA) and rheumatoid factor (RF) will develop in patients with sJIA over the course of the disease. FINDINGS: A single center sample of sJIA patients with follow-up of more than one year was obtained. A retrospective chart survey was used to extract demographic and clinical data as well as presence and titers of ANA and RF at diagnosis and during follow-up. 32 patients were included in the study, with a median age of 4.2 years and median follow-up of 6.0 years. 8/32 patients had ANA titers >= 1:80 at diagnosis, with 22/32 patients showing rising ANA titers with titers >= 1:80 at last follow-up (p =0.001). 10/32 patients had a positive RF at least once during follow-up, compared to 0/32 at diagnosis (p = 0.001). In 5/10 patients, positive RF was documented at least twice, more than twelve weeks apart. Patients treated with TNF antagonists were not significantly more likely to develop positive ANA titers (p = 0.425) or positive RF (p = 0.703). CONCLUSIONS: Patients with sJIA developed increased ANA titers and positive RF over the course of the disease, independent of treatment with TNF antagonists. This might point towards an autoimmune, rather than an autoinflammatory phenotype later in the course of sJIA. PMID- 25114628 TI - Regorafenib: an evidence-based review of its potential in patients with advanced liver cancer. AB - Hepatocellular carcinoma (HCC) is the second-most common cause of cancer-related death in the world. In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options. Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC. Over the last 5 years, several other medications have been tested in Phase III trials. However, they have not shown any added benefit over sorafenib. Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models. After its safety and pharmacological properties was studied in Phase I trials, a Phase II study evaluating the role of Regorafenib in patients with advanced HCC who progressed on sorafenib therapy demonstrated efficacy and a manageable safety profile. A Phase III trial is ongoing, and its result will help us better evaluate the role of Regorafenib in patients with advanced HCC. PMID- 25114629 TI - Structural damage of chicken red blood cells exposed to platinum nanoparticles and cisplatin. AB - Side effects and resistance of cancer cells to cisplatin are major drawbacks to its application, and recently, the possibility of replacing cisplatin with nanocompounds has been considered. Most chemotherapeutic agents are administered intravenously, and comparisons between the interactions of platinum nanoparticles (NP-Pt) and cisplatin with blood compartments are important for future applications. This study investigated structural damage, cell membrane deformation and haemolysis of chicken embryo red blood cells (RBC) after treatment with cisplatin and NP-Pt. Cisplatin (4 MUg/ml) and NP-Pt (2,6 MUg/ml), when incubated with chicken embryo RBC, were detrimental to cell structure and induced haemolysis. The level of haemolytic injury was increased after cisplatin and NP-Pt treatments compared to the control group. Treatment with cisplatin caused structural damage to cell membranes and the appearance of keratocytes, while NP-Pt caused cell membrane deformations (discoid shape of cells was lost) and the formation of knizocytes and echinocytes. This work demonstrated that NP Pt have potential applications in anticancer therapy, but potential toxic side effects must be explored in future preclinical research. PMID- 25114630 TI - Synthesis of mixed-sequence oligonucleotides on mesoporous silicon: chemical strategies and material stability. AB - Rapid screening tests in medical diagnostic and environmental analysis are often based on oligonucleotide biochips. In this paper, we studied the stability of functionalized mesoporous silicon supports in the solid-phase synthesis of oligonucleotides, exploiting several chemical procedures. A 19-mer mixed sequence has been successfully synthesized on aminosilane-modified porous silicon photonic structures. The process and the materials have been characterized by optical reflectivity, atomic force microscopy and high-performance liquid chromatography. PMID- 25114631 TI - Thermal conductivity of highly porous Si in the temperature range 4.2 to 20 K. AB - We report on experimental results of the thermal conductivity k of highly porous Si in the temperature range 4.2 to 20 K, obtained using the direct current (dc) method combined with thermal finite element simulations. The reported results are the first in the literature for this temperature range. It was found that porous Si thermal conductivity at these temperatures shows a plateau-like temperature dependence similar to that obtained in glasses, with a constant k value as low as 0.04 W/m.K. This behavior is attributed to the presence of a majority of non propagating vibrational modes, resulting from the nanoscale fractal structure of the material. By examining the fractal geometry of porous Si and its fractal dimensionality, which was smaller than two for the specific porous Si material used, we propose that a band of fractons (the localized vibrational excitations of a fractal lattice) is responsible for the observed plateau. The above results complement previous results by the authors in the temperature range 20 to 350 K. In this temperature range, a monotonic increase of k with temperature is observed, fitted with simplified classical models. The extremely low thermal conductivity of porous Si, especially at cryogenic temperatures, makes this material an excellent substrate for Si-integrated microcooling devices (micro coldplate). PACS: 61.43.-j; 63.22.-m; 65.8.-g. PMID- 25114632 TI - Efficiency enhancement of non-selenized Cu(In,Ga)Se2 solar cells employing scalable low-cost antireflective coating. AB - In this study, a non-selenized CuInGaSe2 (CIGS) solar device with textured zinc oxide (ZnO) antireflection coatings was studied. The ZnO nanostructure was fabricated by a low-temperature aqueous solution deposition method. With controlling the morphology of the solution-grown tapered ZnO nanorod coatings, the average reflectance of the CIGS solar device decreased from 8.6% to 2.1%, and the energy conversion efficiency increased from 9.1% to 11.1%. The performance improvement in the CuInGaSe2 thin-film solar cell was well explained due to the gradual increase of the refractive index between air and the top electrode of solar cell device by the insertion of the ZnO nanostructure. The results demonstrate a potential application of the ZnO nanostructure array for efficient solar device technology. PMID- 25114634 TI - Growth of arrays of oriented epitaxial platinum nanoparticles with controlled size and shape by natural colloidal lithography. AB - We developed a method for production of arrays of platinum nanocrystals of controlled size and shape using templates from ordered silica bead monolayers. Silica beads with nominal sizes of 150 and 450 nm were self-assembled into monolayers over strontium titanate single crystal substrates. The monolayers were used as shadow masks for platinum metal deposition on the substrate using the three-step evaporation technique. Produced arrays of epitaxial platinum islands were transformed into nanocrystals by annealing in a quartz tube in nitrogen flow. The shape of particles is determined by the substrate crystallography, while the size of the particles and their spacing are controlled by the size of the silica beads in the monolayer mask. As a proof of concept, arrays of platinum nanocrystals of cubooctahedral shape were prepared on (100) strontium titanate substrates. The nanocrystal arrays were characterized by atomic force microscopy, scanning electron microscopy, and synchrotron X-ray diffraction techniques. PMID- 25114633 TI - Nitric oxide-releasing porous silicon nanoparticles. AB - In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment. PMID- 25114636 TI - Magnetic field dependence of singlet oxygen generation by nanoporous silicon. AB - Energy transfer from photoexcited excitons localized in silicon nanoparticles to adsorbed oxygen molecules excites them to the reactive singlet spin state. This process has been studied experimentally as a function of nanoparticle size and applied external magnetic field as a test of the accepted understanding of this process in terms of the exchange coupling between the nano-Si exciton and the adsorbed O2 molecules. PMID- 25114635 TI - Preparation and nanoencapsulation of l-asparaginase II in chitosan tripolyphosphate nanoparticles and in vitro release study. AB - This paper describes the production, purification, and immobilization of l asparaginase II (ASNase II) in chitosan nanoparticles (CSNPs). ASNase II is an effective antineoplastic agent, used in the acute lymphoblastic leukemia chemotherapy. Cloned ASNase II gene (ansB) in pAED4 plasmid was transformed into Escherichia coli BL21pLysS (DE3) competent cells and expressed under optimal conditions. The lyophilized enzyme was loaded into CSNPs by ionotropic gelation method. In order to get optimal entrapment efficiency, CSNP preparation, chitosan/tripolyphosphate (CS/TPP) ratio, and protein loading were investigated. ASNase II loading into CSNPs was confirmed by Fourier transform infrared (FTIR) spectroscopy, and morphological observation was carried out by transmission electron microscopy. Three absolute CS/TPP ratios were studied. Entrapment efficiency and loading capacity increased with increasing CS and TPP concentration. The best ratio was applied for obtaining optimal ASNase II-loaded CSNPs with the highest entrapment efficiency. Size, zeta potential, entrapment efficiency, and loading capacity of the optimal ASNase II-CSNPs were 340 +/- 12 nm, 21.2 +/- 3 mV, 76.2% and 47.6%, respectively. The immobilized enzyme showed an increased in vitro half-life in comparison with the free enzyme. The pH and thermostability of the immobilized enzyme was comparable with the free enzyme. This study leads to a better understanding of how to prepare CSNPs, how to achieve high encapsulation efficiency for a high molecular weight protein, and how to prolong the release of protein from CSNPs. A conceptual understanding of biological responses to ASNase II-loaded CSNPs is needed for the development of novel methods of drug delivery. PMID- 25114637 TI - Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear. AB - Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders. PMID- 25114638 TI - Fabrication and sensing behavior of one-dimensional ZnO-Zn2GeO4 heterostructures. AB - Well-crystalline one-dimensional ZnO-Zn2GeO4 (ZGO) heterostructures were successfully synthesized using a high-temperature solid-state reaction between the ZnO and Ge layers of ZnO-Ge core-shell nanostructures. The polycrystalline ZGO crystallites had a thickness in the range of 17 to 26 nm. The high temperature solid-state reaction induced grooves and crystal defects on the surfaces of the ZGO crystallites. The sensors made from the ZnO-ZGO heterostructures exhibited a marked photocurrent response to UV light at room temperature and a gas sensing response to acetone gas at 325 degrees C. The observed sensing properties are attributed to the rugged surface of the ZGO heterointerfaces between ZnO and ZGO, surface crystal defects of ZGO, and cross linked contact regions of ZnO-ZGO. PMID- 25114639 TI - Controlled atom transfer radical polymerization of MMA onto the surface of high density functionalized graphene oxide. AB - We report on the grafting of poly(methyl methacrylate) (PMMA) onto the surface of high-density functionalized graphene oxides (GO) through controlled radical polymerization (CRP). To increase the density of surface grafting, GO was first diazotized (DGO), followed by esterification with 2-bromoisobutyryl bromide, which resulted in an atom transfer radical polymerization (ATRP) initiator functionalized DGO-Br. The functionalized DGO-Br was characterized by X-ray photoelectron spectroscopy (XPS), Raman, and XRD patterns. PMMA chains were then grafted onto the DGO-Br surface through a 'grafting from' technique using ATRP. Gel permeation chromatography (GPC) results revealed that polymerization of methyl methacrylate (MMA) follows CRP. Thermal studies show that the resulting graphene-PMMA nanocomposites have higher thermal stability and glass transition temperatures (T g) than those of pristine PMMA. PMID- 25114640 TI - Size evolution of ion beam synthesized Pb nanoparticles in Al. AB - The size evolution of Pb nanoparticles (NPs) synthesized by ion implantation in an epitaxial Al film has been experimentally investigated. The average radius R of Pb NPs was determined as a function of implantation fluence f. The R(f) data were analyzed using various growth models. Our observations suggest that the size evolution of Pb NPs is controlled by the diffusion-limited growth kinetics (R (2)?f). With increasing implantation current density, the diffusion coefficient of Pb atoms in Al is evident to be enhanced. By a comparative analysis of the R(f) data, values of the diffusion coefficient of Pb in Al were obtained. PMID- 25114641 TI - Low-temperature growth of highly crystalline beta-Ga2O3 nanowires by solid-source chemical vapor deposition. AB - Growing Ga2O3 dielectric materials at a moderately low temperature is important for the further development of high-mobility III-V semiconductor-based nanoelectronics. Here, beta-Ga2O3 nanowires are successfully synthesized at a relatively low temperature of 610 degrees C by solid-source chemical vapor deposition employing GaAs powders as the source material, which is in a distinct contrast to the typical synthesis temperature of above 1,000 degrees C as reported by other methods. In this work, the prepared beta-Ga2O3 nanowires are mainly composed of Ga and O elements with an atomic ratio of approximately 2:3. Importantly, they are highly crystalline in the monoclinic structure with varied growth orientations in low-index planes. The bandgap of the beta-Ga2O3 nanowires is determined to be 251 nm (approximately 4.94 eV), in good accordance with the literature. Also, electrical characterization reveals that the individual nanowire has a resistivity of up to 8.5 * 10(7) Omega cm, when fabricated in the configuration of parallel arrays, further indicating the promise of growing these highly insulating Ga2O3 materials in this III-V nanowire-compatible growth condition. PACS: 77.55.D; 61.46.Km; 78.40.Fy. PMID- 25114643 TI - Tailoring the grooved texture of electrospun polystyrene nanofibers by controlling the solvent system and relative humidity. AB - In this study, we have successfully fabricated electrospun polystyrene (PS) nanofibers having a diameter of 326 +/- 50 nm with a parallel grooved texture using a mixed solvent of tetrahydrofuran (THF) and N,N-dimethylformamide (DMF). We discovered that solvent system, solution concentration, and relative humidity were the three key factors to the formation of grooved texture and the diameter of nanofibers. We demonstrated that grooved nanofibers with desired properties (e.g., different numbers of grooves, widths between two adjacent grooves, and depths of grooves) could be electrospun under certain conditions. When THF/DMF ratio was higher than 2:1, the formation mechanism of single grooved texture should be attributed to the formation of voids on the jet surface at the early stage of electrospinning and subsequent elongation and solidification of the voids into a line surface structure. When THF/DMF ratio was 1:1, the formation mechanism of grooved texture should be ascribed to the formation of wrinkled surface on the jet surface at the early stage of electrospinning and subsequent elongation into a grooved texture. Such findings can serve as guidelines for the preparation of grooved nanofibers with desired secondary morphology. PMID- 25114642 TI - Graphene as a transparent conducting and surface field layer in planar Si solar cells. AB - This work presents an experimental and finite difference time domain (FDTD) simulation-based study on the application of graphene as a transparent conducting layer on a planar and untextured crystalline p-n silicon solar cell. A high quality monolayer graphene with 97% transparency and 350 Omega/? sheet resistance grown by atmospheric pressure chemical vapor deposition method was transferred onto planar Si cells. An increase in efficiency from 5.38% to 7.85% was observed upon deposition of graphene onto Si cells, which further increases to 8.94% upon SiO2 deposition onto the graphene/Si structure. A large increase in photon conversion efficiency as a result of graphene deposition shows that the electronic interaction and the presence of an electric field at the graphene/Si interface together play an important role in this improvement and additionally lead to a reduction in series resistance due to the conducting nature of graphene. PMID- 25114644 TI - Well-ordered polymer nano-fibers with self-cleaning property by disturbing crystallization process. AB - Bionic self-cleaning surfaces with well-ordered polymer nano-fibers are firstly fabricated by disturbing crystallization during one-step coating-curing process. Orderly thin (100 nm) and long (5-10 MUm) polymer nano-fibers with a certain direction are fabricated by external macroscopic force (F blow) interference introduced by H2 gas flow, leading to superior superhydrophobicity with a water contact angle (WCA) of 170 degrees and a water sliding angle (WSA) of 0-1 degrees . In contrast, nano-wires and nano-bridges (1-8 MUm in length/10-80 nm in width) are generated by "spinning/stretching" under internal microscopic force (F T) interference due to significant temperature difference in the non-uniform cooling medium. The findings provide a novel theoretical basis for controllable polymer "bionic lotus" surface and will further promote practical application in many engineering fields such as drag-reduction and anti-icing. PMID- 25114645 TI - Nylon 6 electrospun nanofibers mat as effective sorbent for the removal of estrogens: kinetic and thermodynamic studies. AB - Nylon 6 electrospun nanofibers mat was prepared via electrospinning for the removal of three estrogens, namely, diethylstilbestrol (DES), dienestrol (DS), and hexestrol (HEX) from aqueous solution. Static adsorption as well as the dynamic adsorption was evaluated by means of batch and dynamic disk flow mode, respectively. The kinetic study indicated that the adsorption of the target compounds could be well fitted by the pseudo-second-order equation, suggesting the intra-particle/membrane diffusion process as the rate-limiting step of the adsorption process. The adsorption equilibrium data were all fitted well to the Freundlich isotherm models, with a maximum adsorption capacity values in the range of 97.71 to 208.95 mg/g, which can be compared to or moderately higher than other sorbents published in the literatures. The dynamic disk mode studies indicated that the mean removal yields of three model estrogens were over 95% with a notable smaller amount of adsorbent (4 mg). Thermodynamic study revealed that the adsorption process was exothermic and spontaneous in nature. Desorption results showed that the adsorption capacity can remain up to 80% after seven times usage. It was suggested that Nylon 6 electrospun nanofibers mat has great potential as a novel effective sorbent material for estrogens removal. PMID- 25114646 TI - Redistribution of elements of metals in plant tissues under treatment by non ionic colloidal solution of biogenic metal nanoparticles. AB - The content of metal elements in plant tissues of 10-day wheat seedlings after seed pre-treatment and foliar treatment with non-ionic colloidal solution of metal nanoparticles (Fe, Mn, Cu, Zn) was determined by an atomic absorption spectrometer. It was shown that metal nanoparticles due to their physical properties (nanoscale and uncharged state) were capable of penetrating rapidly into plant cells and optimizing plant metabolic processes at the early stages of growth and development. PMID- 25114647 TI - The obtaining of high-density specimens and analysis of mechanical strength characteristics of a composite based on ZrO2-WC nanopowders. AB - The structures, processes of shrinkage, and phase composition of the compact system ZrO2-WC, obtained by hot pressing with the transmission of high current, are considered in the article. We found that as a result of compaction, the ZrO2 WC-ceramics have uniform density distribution, with the following optimal mode consolidation values T = 1,350 degrees C, P = 30 MPa and t = 2 min. These conditions allow us to achieve the best combination of ceramic properties by criteria density and strength. PMID- 25114648 TI - Scandium effect on the luminescence of Er-Sc silicates prepared from multi nanolayer films. AB - Polycrystalline Er-Sc silicates (Er x Sc2-x Si2O7 and Er x Sc2-x SiO5) were fabricated using multilayer nanostructured films of Er2O3/SiO2/Sc2O3 deposited on SiO2/Si substrates by RF sputtering and thermal annealing at high temperature. The films were characterized by synchrotron radiation grazing incidence X-ray diffraction, cross-sectional transmission electron microscopy, energy-dispersive X-ray spectroscopy, and micro-photoluminescence measurements. The Er-Sc silicate phase Er x Sc2-x Si2O7 is the dominant film, and Er and Sc are homogeneously distributed after thermal treatment because of the excess of oxygen from SiO2 interlayers. The Er concentration of 6.7 * 10(21) atoms/cm(3) was achieved due to the presence of Sc that dilutes the Er concentration and generates concentration quenching. During silicate formation, the erbium diffusion coefficient in the silicate phase is estimated to be 1 * 10(-15) cm(2)/s at 1,250 degrees C. The dominant Er x Sc2 - x Si2O7 layer shows a room-temperature photoluminescence peak at 1,537 nm with the full width at half maximum (FWHM) of 1.6 nm. The peak emission shift compared to that of the Y-Er silicate (where Y and Er have almost the same ionic radii) and the narrow FWHM are due to the small ionic radii of Sc(3+) which enhance the crystal field strength affecting the optical properties of Er(3+) ions located at the well-defined lattice sites of the Sc silicate. The Er-Sc silicate with narrow FWHM opens a promising way to prepare photonic crystal light-emitting devices. PMID- 25114649 TI - Beneficial defects: exploiting the intrinsic polishing-induced wafer roughness for the catalyst-free growth of Ge in-plane nanowires. AB - We outline a metal-free fabrication route of in-plane Ge nanowires on Ge(001) substrates. By positively exploiting the polishing-induced defects of standard quality commercial Ge(001) wafers, micrometer-length wires are grown by physical vapor deposition in ultra-high-vacuum environment. The shape of the wires can be tailored by the epitaxial strain induced by subsequent Si deposition, determining a progressive transformation of the wires in SiGe faceted quantum dots. This shape transition is described by finite element simulations of continuous elasticity and gives hints on the equilibrium shape of nanocrystals in the presence of tensile epitaxial strain. PACS: 81.07.Gf; 68.35.bg; 68.35.bj; 62.23.Eg. PMID- 25114650 TI - Complex microstructures of ABC triblock copolymer thin films directed by polymer brushes based on self-consistent field theory. AB - The morphology and the phase diagram of ABC triblock copolymer thin film directed by polymer brushes are investigated by the self-consistent field theory in three dimensions. The polymer brushes coated on the substrate can be used as a good soft template to tailor the morphology of the block copolymer thin films compared with those on the hard substrates. The polymer brush is identical with the middle block B. By continuously changing the composition of the block copolymer, the phase diagrams are constructed for three cases with the fixed film thickness and the brush density: identical interaction parameters, frustrated and non frustrated cases. Some ordered complex morphologies are observed: parallel lamellar phase with hexagonally packed pores at surfaces (LAM3 (ll) -HFs), perpendicular lamellar phase with cylinders at the interface (LAM(?)-CI), and perpendicular hexagonally packed cylinders phase with rings at the interface (C2 (?)-RI). A desired direction (perpendicular or parallel to the coated surfaces) of lamellar phases or cylindrical phases can be obtained by varying the composition and the interactions between different blocks. The phase diagram of ABC triblock copolymer thin film wetted between the polymer brush-coated surfaces is very useful in designing the directed pattern of ABC triblock copolymer thin film. PMID- 25114651 TI - Low-cost carbon-silicon nanocomposite anodes for lithium ion batteries. AB - The specific energy of the existing lithium ion battery cells is limited because intercalation electrodes made of activated carbon (AC) materials have limited lithium ion storage capacities. Carbon nanotubes, graphene, and carbon nanofibers are the most sought alternatives to replace AC materials but their synthesis cost makes them highly prohibitive. Silicon has recently emerged as a strong candidate to replace existing graphite anodes due to its inherently large specific capacity and low working potential. However, pure silicon electrodes have shown poor mechanical integrity due to the dramatic expansion of the material during battery operation. This results in high irreversible capacity and short cycle life. We report on the synthesis and use of carbon and hybrid carbon-silicon nanostructures made by a simplified thermo-mechanical milling process to produce low-cost high-energy lithium ion battery anodes. Our work is based on an abundant, cost-effective, and easy-to-launch source of carbon soot having amorphous nature in combination with scrap silicon with crystalline nature. The carbon soot is transformed in situ into graphene and graphitic carbon during mechanical milling leading to superior elastic properties. Micro-Raman mapping shows a well-dispersed microstructure for both carbon and silicon. The fabricated composites are used for battery anodes, and the results are compared with commercial anodes from MTI Corporation. The anodes are integrated in batteries and tested; the results are compared to those seen in commercial batteries. For quick laboratory assessment, all electrochemical cells were fabricated under available environment conditions and they were tested at room temperature. Initial electrochemical analysis results on specific capacity, efficiency, and cyclability in comparison to currently available AC counterpart are promising to advance cost-effective commercial lithium ion battery technology. The electrochemical performance observed for carbon soot material is very interesting given the fact that its production cost is away cheaper than activated carbon. The cost of activated carbon is about $15/kg whereas the cost to manufacture carbon soot as a by-product from large-scale milling of abundant graphite is about $1/kg. Additionally, here, we propose a method that is environmentally friendly with strong potential for industrialization. PMID- 25114652 TI - Large-diameter titanium dioxide nanotube arrays as a scattering layer for high efficiency dye-sensitized solar cell. AB - Large-sized titanium dioxide (TiO2) nanotube arrays with an outer diameter of approximately 500 nm have been successfully synthesized by potentiostatic anodization at 180 V in a used electrolyte with the addition of 1.5 M lactic acid. It is found that the synthesized large-diameter TiO2 nanotube array shows a superior light scattering ability, which can be used as a light scattering layer to significantly enhance the efficiency of TiO2 nanoparticle-based dye-sensitized solar cells from 5.18% to 6.15%. The remarkable light scattering ability makes the large-diameter TiO2 nanotube array a promising candidate for light management in dye-sensitized solar cells (DSSCs). PMID- 25114653 TI - Validation of a Janus role of methotrexate-based PEGylated chitosan nanoparticles in vitro. AB - Recently, methotrexate (MTX) has been used to target to folate (FA) receptor overexpressing cancer cells for targeted drug delivery. However, the systematic evaluation of MTX as a Janus-like agent has not been reported before. Here, we explored the validity of using MTX playing an early-phase cancer-specific targeting ligand cooperated with a late-phase therapeutic anticancer agent based on the PEGylated chitosan (CS) nanoparticles (NPs) as drug carriers. Some advantages of these nanoscaled drug delivery systems are as follows: (1) the NPs can ensure minimal premature release of MTX at off-target site to reduce the side effects to normal tissue; (2) MTX can function as a targeting ligand at target site prior to cellular uptake; and (3) once internalized by the target cell, the NPs can function as a prodrug formulation, releasing biologically active MTX inside the cells. The (MTX + PEG)-CS-NPs presented a sustained/proteases-mediated drug release. More importantly, compared with the PEG-CS-NPs and (FA + PEG)-CS NPs, the (MTX + PEG)-CS-NPs showed a greater cellular uptake. Furthermore, the (MTX + PEG)-CS-NPs demonstrated a superior cytotoxicity compare to the free MTX. Our findings therefore validated that the MTX-loaded PEGylated CS-NPs can simultaneously target and treat FA receptor-overexpressing cancer cells. PMID- 25114654 TI - Internal resistor of multi-functional tunnel barrier for selectivity and switching uniformity in resistive random access memory. AB - In this research, we analyzed the multi-functional role of a tunnel barrier that can be integrated in devices. This tunnel barrier, acting as an internal resistor, changes its resistance with applied bias. Therefore, the current flow in the devices can be controlled by a tunneling mechanism that modifies the tunnel barrier thickness for non-linearity and switching uniformity of devices. When a device is in a low-resistance state, the tunnel barrier controls the current behavior of the device because most of the bias is applied to the tunnel barrier owing to its higher resistance. Furthermore, the tunnel barrier induces uniform filament formation during set operation with the tunnel barrier controlling the current flow. PMID- 25114655 TI - Green synthesis of protein capped silver nanoparticles from phytopathogenic fungus Macrophomina phaseolina (Tassi) Goid with antimicrobial properties against multidrug-resistant bacteria. AB - In recent years, green synthesis of nanoparticles, i.e., synthesizing nanoparticles using biological sources like bacteria, algae, fungus, or plant extracts have attracted much attention due to its environment-friendly and economic aspects. The present study demonstrates an eco-friendly and low-cost method of biosynthesis of silver nanoparticles using cell-free filtrate of phytopathogenic fungus Macrophomina phaseolina. UV-visible spectrum showed a peak at 450 nm corresponding to the plasmon absorbance of silver nanoparticles. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and transmission electron microscopy (TEM) revealed the presence of spherical silver nanoparticles of the size range 5 to 40 nm, most of these being 16 to 20 nm in diameter. X-ray diffraction (XRD) spectrum of the nanoparticles exhibited 2theta values corresponding to silver nanoparticles. These nanoparticles were found to be naturally protein coated. SDS-PAGE analysis showed the presence of an 85-kDa protein band responsible for capping and stabilization of the silver nanoparticles. Antimicrobial activities of the silver nanoparticles against human as well as plant pathogenic multidrug-resistant bacteria were assayed. The particles showed inhibitory effect on the growth kinetics of human and plant bacteria. Furthermore, the genotoxic potential of the silver nanoparticles with increasing concentrations was evaluated by DNA fragmentation studies using plasmid DNA. PMID- 25114656 TI - Van der Waals epitaxy and characterization of hexagonal boron nitride nanosheets on graphene. AB - Graphene is highly sensitive to environmental influences, and thus, it is worthwhile to deposit protective layers on graphene without impairing its excellent properties. Hexagonal boron nitride (h-BN), a well-known dielectric material, may afford the necessary protection. In this research, we demonstrated the van der Waals epitaxy of h-BN nanosheets on mechanically exfoliated graphene by chemical vapor deposition, using borazine as the precursor to h-BN. The h-BN nanosheets had a triangular morphology on a narrow graphene belt but a polygonal morphology on a larger graphene film. The h-BN nanosheets on graphene were highly crystalline, except for various in-plane lattice orientations. Interestingly, the h-BN nanosheets preferred to grow on graphene than on SiO2/Si under the chosen experimental conditions, and this selective growth spoke of potential promise for application to the preparation of graphene/h-BN superlattice structures fabricated on SiO2/Si. PMID- 25114657 TI - Facile synthesis and electrochemical performances of hollow graphene spheres as anode material for lithium-ion batteries. AB - The hollow graphene oxide spheres have been successfully fabricated from graphene oxide nanosheets utilizing a water-in-oil emulsion technique, which were prepared from natural flake graphite by oxidation and ultrasonic treatment. The hollow graphene oxide spheres were reduced to hollow graphene spheres at 500 degrees C for 3 h under an atmosphere of Ar(95%)/H2(5%). The first reversible specific capacity of the hollow graphene spheres was as high as 903 mAh g(-1) at a current density of 50 mAh g(-1). Even at a high current density of 500 mAh g(-1), the reversible specific capacity remained at 502 mAh g(-1). After 60 cycles, the reversible capacity was still kept at 652 mAh g(-1) at the current density of 50 mAh g(-1). These results indicate that the prepared hollow graphene spheres possess excellent electrochemical performances for lithium storage. The high rate performance of hollow graphene spheres thanks to the hollow structure, thin and porous shells consisting of graphene sheets. PACS: 81.05.ue; 61.48.Gh; 72.80.Vp. PMID- 25114658 TI - Current-voltage characteristics of nanoplatelet-based conductive nanocomposites. AB - In this study, a numerical modeling approach was used to investigate the current voltage behavior of conductive nanoplatelet-based nanocomposites. A three dimensional continuum Monte Carlo model was employed to randomly disperse the nanoplatelets in a cubic representative volume element. A nonlinear finite element-based model was developed to evaluate the electrical behavior of the nanocomposite for different levels of the applied electric field. Also, the effect of filler loading on nonlinear conductivity behavior of nanocomposites was investigated. The validity of the developed model was verified through qualitative comparison of the simulation results with results obtained from experimental works. PMID- 25114659 TI - Conductance modulation of charged lipid bilayer using electrolyte-gated graphene field effect transistor. AB - Graphene is an attention-grabbing material in electronics, physics, chemistry, and even biology because of its unique properties such as high surface-area-to volume ratio. Also, the ability of graphene-based materials to continuously tune charge carriers from holes to electrons makes them promising for biological applications, especially in lipid bilayer-based sensors. Furthermore, changes in charged lipid membrane properties can be electrically detected by a graphene based electrolyte-gated graphene field effect transistor (GFET). In this paper, a monolayer graphene-based GFET with a focus on the conductance variation caused by membrane electric charges and thickness is studied. Monolayer graphene conductance as an electrical detection platform is suggested for neutral, negative, and positive electric-charged membrane. The electric charge and thickness of the lipid bilayer (Q LP and L LP) as a function of carrier density are proposed, and the control parameters are defined. Finally, the proposed analytical model is compared with experimental data which indicates good overall agreement. PMID- 25114660 TI - Controlled nanodot fabrication by rippling polycarbonate surface using an AFM diamond tip. AB - The single scratching test of polymer polycarbonate (PC) sample surface using an atomic force microscope (AFM) diamond tip for fabricating ripple patterns has been studied with the focus on the evaluation of the effect of the tip scratching angle on the pattern formation. The experimental results indicated that the different oriented ripples can be easily machined by controlling the scratching angles of the AFM. And, the effects of the normal load and the feed on the ripples formation and their periods were also studied. Based on the ripple pattern formation, we firstly proposed a two-step scratching method to fabricate controllable and oriented complex three-dimensional (3D) nanodot arrays. These typical ripple formations can be described via a stick-slip and crack formation process. PMID- 25114661 TI - Electrical behavior and positive temperature coefficient effect of graphene/polyvinylidene fluoride composites containing silver nanowires. AB - Polyvinylidene fluoride (PVDF) composites filled with in situ thermally reduced graphene oxide (TRG) and silver nanowire (AgNW) were prepared using solution mixing followed by coagulation and thermal hot pressing. Binary TRG/PVDF nanocomposites exhibited small percolation threshold of 0.12 vol % and low electrical conductivity of approximately 10(-7) S/cm. Hybridization of TRGs with AgNWs led to a significant improvement in electrical conductivity due to their synergistic effect in conductivity. The bulk conductivity of hybrids was higher than a combined total conductivity of TRG/PVDF and AgNW/PVDF composites at the same filler loading. Furthermore, the resistivity of hybrid composites increased with increasing temperature, giving rise to a positive temperature coefficient (PTC) effect at the melting temperature of PVDF. The 0.04 vol % TRG/1 vol % AgNW/PVDF hybrid exhibited pronounced PTC behavior, rendering this composite an attractive material for making current limiting devices and temperature sensors. PMID- 25114663 TI - Integration of care systems in Portugal: anatomy of recent reforms. AB - BACKGROUND: Integrated care is increasingly present in the agenda of policy makers, health professionals and researchers as a way to improve care services in relation to access, quality, user satisfaction and efficiency. These are overarching objectives of most sectoral reforms. However, health care and social care services and systems are more and more dependent on the performance of each other, imposing the logic of network. Demographic, epidemiologic and cultural changes result in pressure to increase efficiency and efficacy of services and organisations in both sectors and that is why integrated care has become so relevant in the last years. METHODS: We first used concept maps to organise and systematise information that we had gathered through deep literature review in order to set a framework where to base the subsequent work. Then, we interviewed informants at several levels of the health and social care systems and we built a list of major recent reforms addressing integrated care in Portugal. In a third step, we conducted two independent focus groups where those reforms were discussed and evaluated within the context of the concepts and frameworks identified from the literature. Results were confronted and reconciled, giving place to a list of requisites and guidelines that oriented further search for documentation on those reforms. RESULTS: Several important health reforms are in course in primary and hospital care in Portugal, while a so-called third level of care has been introduced with the launch of the National Network of Long-Term Integrated Care (RNCCI - Rede Nacional de Cuidados Continuados Integrados). The social care sector has itself been a subject of alternative models springing from opposite political orientations. All these changes are having repercussions on the way the systems work with each other as they are leading to ongoing and ill evaluated reformulations on the way they are governed, financed, structured and operated. CONCLUSIONS: Care integration is not absent from policy-making and implementation endeavour in Portugal. However, recurrent issues seem to be consistently hampering the efforts regarding the integration of care in the country. It is urgent to assess current situation as experienced by those closely involved and directly affected. PMID- 25114662 TI - Validation of a blood protein signature for non-small cell lung cancer. AB - BACKGROUND: CT screening for lung cancer is effective in reducing mortality, but there are areas of concern, including a positive predictive value of 4% and development of interval cancers. A blood test that could manage these limitations would be useful, but development of such tests has been impaired by variations in blood collection that may lead to poor reproducibility across populations. RESULTS: Blood-based proteomic profiles were generated with SOMAscan technology, which measured 1033 proteins. First, preanalytic variability was evaluated with Sample Mapping Vectors (SMV), which are panels of proteins that detect confounders in protein levels related to sample collection. A subset of well collected serum samples not influenced by preanalytic variability was selected for discovery of lung cancer biomarkers. The impact of sample collection variation on these candidate markers was tested in the subset of samples with higher SMV scores so that the most robust markers could be used to create disease classifiers. The discovery sample set (n = 363) was from a multi-center study of 94 non-small cell lung cancer (NSCLC) cases and 269 long-term smokers and benign pulmonary nodule controls. The analysis resulted in a 7-marker panel with an AUC of 0.85 for all cases (68% adenocarcinoma, 32% squamous) and an AUC of 0.93 for squamous cell carcinoma in particular. This panel was validated by making blinded predictions in two independent cohorts (n = 138 in the first validation and n = 135 in the second). The model was recalibrated for a panel format prior to unblinding the second cohort. The AUCs overall were 0.81 and 0.77, and for squamous cell tumors alone were 0.89 and 0.87. The estimated negative predictive value for a 15% disease prevalence was 93% overall and 99% for squamous lung tumors. The proteins in the classifier function in destruction of the extracellular matrix, metabolic homeostasis and inflammation. CONCLUSIONS: Selecting biomarkers resistant to sample processing variation led to robust lung cancer biomarkers that performed consistently in independent validations. They form a sensitive signature for detection of lung cancer, especially squamous cell histology. This non-invasive test could be used to improve the positive predictive value of CT screening, with the potential to avoid invasive evaluation of nonmalignant pulmonary nodules. PMID- 25114664 TI - Do telemonitoring projects of heart failure fit the Chronic Care Model? AB - This study describes the characteristics of extramural and transmural telemonitoring projects on chronic heart failure in Belgium. It describes to what extent these telemonitoring projects coincide with the Chronic Care Model of Wagner. BACKGROUND: The Chronic Care Model describes essential components for high-quality health care. Telemonitoring can be used to optimise home care for chronic heart failure. It provides a potential prospective to change the current care organisation. METHODS: This qualitative study describes seven non-invasive home-care telemonitoring projects in patients with heart failure in Belgium. A qualitative design, including interviews and literature review, was used to describe the correspondence of these home-care telemonitoring projects with the dimensions of the Chronic Care Model. RESULTS: The projects were situated in primary and secondary health care. Their primary goal was to reduce the number of readmissions for chronic heart failure. None of these projects succeeded in a final implementation of telemonitoring in home care after the pilot phase. Not all the projects were initiated to accomplish all of the dimensions of the Chronic Care Model. A central role for the patient was sparse. CONCLUSION: Limited financial resources hampered continuation after the pilot phase. Cooperation and coordination in telemonitoring appears to be major barriers but are, within primary care as well as between the lines of care, important links in follow-up. This discrepancy can be prohibitive for deployment of good chronic care. Chronic Care Model is recommended as basis for future. PMID- 25114665 TI - Identification of mechanisms enabling integrated care for patients with chronic diseases: a literature review. AB - INTRODUCTION: Notwithstanding care for chronically ill patients requires a shift towards care that is well coordinated and focused on prevention and self-care, the concept of integrated care lacks specificity and clarity. This article presents a literature review to identify mechanisms for achieving integrated care objectives. THEORY AND METHODS: Existing models often present a large variety of dimensions, archetypes and categories of integration without specifying them. Models and programmes describing integrated care for chronic diseases were reviewed. Data were extracted related to objectives and clusters of mechanisms of integration. RESULTS: Thirty-four studies presented four objectives: functional, organisational, professional and service integration. We categorised approaches and interventions to achieve these objectives by strategy and clusters of 'mechanisms of integration': degree, patient centredness and normative aspects. CONCLUSIONS AND DISCUSSION: The clarification of mechanisms to achieve objectives of integrated care as presented may be used as starting point for the development and refinement of integrated care programmes, including methodological grounding of their evaluation. Given that most studies reviewed lack both empirical data and descriptions of the methods used, future research needs to close these gaps. Validation of the findings by a large panel of experts is suggested as recommendation to work towards a grounded framework. PMID- 25114666 TI - A neuropsychiatric complication of oligomenorrhea according to iranian traditional medicine. AB - Oligomenorrhea, a prevalent disease with serious complications, has been declared in the Avicenna traditional medicine in detail. Avicenna in his famous book, Cannon of Medicine, presents a syndrome termed 'uterine strangulation', as a complication of menstrual bleeding cessation and lack of sexual satisfaction. We have explained this syndrome from both traditional and conventional medicine viewpoints to propose a new hypothesis for diagnosis and treatment of women with oligomenorrhea and systemic signs/symptoms admitting to clinics for further evaluation. This hypothesis definitely needs to be further assessed and confirmed by strong clinical trials. PMID- 25114667 TI - Evaluating the effects of Escanbil (Calligonum) extract on the expression level of Catsper gene variants and sperm motility in aging male mice. AB - BACKGROUND: Catsper proteins are responsible for entering Ca(2+) to the cell and play an important role in sperm motility and male fertility. Antioxidants are vital for sperm motility too. Escanbil (Calligonum) extract possess some of the important antioxidant like Catechin and Quercetin. OBJECTIVE: Here we investigated the effects of Escanbil (Calligonum) extract on the sperm parameters and the expressing of Catsper gene in aging male mice. MATERIALS AND METHODS: In this animal study, firstly, dose response was performed by using these three doses of Escanbil (Calligonum) (10, 30 and 50 mg/kg). 5 mice in each group were considered and Intra Peritoneal injection was done for 5 weeks. the sperm parameters analyzed and dUTP nick end labeling (TUNEL )staining was done. 30 mg/kg dose was considered as optimum dose. Secondly: fifteen aging male mice (11 13 months) were divided into three groups: control, sham and experiment. The experiments were injected Intra peritonealy with Escanbil (Calligonum) extract (30mg/kg) weekly for up to 5 weeks. The sham group was injected Intra Peritoneal (DMSO). Sperm parameters were analyzed. Expression of Catsper genes was analyzed by Real time PCR. RESULTS: Our results showed that after Escanbil (Calligonum) treatment (30 mg/kg), the sperm parameters were improved in experimental group (p<0.05). Our data showed that there was a statistical significance difference between the expressions of Catsper 2, 4 in aging experiment group comparison with aging control group (p<0.05). CONCLUSION: We investigated that the Escanbil (Calligonum) extract (30 mg/kg) can improve sperm parameters and change the expression of Catsper genes in aging male mice. This herbal extract can be used as an antioxidant component for clinical usages. PMID- 25114668 TI - Recurrent IVF failure and hereditary thrombophilia. AB - BACKGROUND: The largest percentage of failed invitro fertilization (IVF (cycles, are due to lack of implantation. As hereditary thrombophilia can cause in placentation failure, it may have a role in recurrent IVF failure. OBJECTIVE: Aim of this case-control study was to determine whether hereditary thrombophilia is more prevalent in women with recurrent IVF failures. MATERIALS AND METHODS: Case group comprised 96 infertile women, with a history of recurrent IVF failure. Control group was comprised of 95 healthy women with proven fertility who had conceived spontaneously. All participants were assessed for the presence of inherited thrombophilias including: factor V Leiden, methilen tetrahydrofolate reductase (MTHFR) mutation, prothrombin mutation, homocystein level, protein S and C deficiency, antithrombin III (AT-III) deficiency and plasminogen activator inhibitor-1 (PAI-1) mutation. Presence of thrombophilia was compared between groups. RESULTS: Having at least one thrombophilia known as a risk factor for recurrent IVF failure (95% CI=1.74-5.70, OR=3.15, p=0.00). Mutation of factor V Leiden (95% CI=1.26-10.27, OR=3.06, P=0.01) and homozygote form of MTHFR mutation (95% CI=1.55-97.86, OR=12.33, p=0.05) were also risk factors for recurrent IVF failure. However, we could not find significant difference in other inherited thrombophilia's. CONCLUSION: Inherited thrombophilia is more prevalent in women with recurrent IVF failure compared with healthy women. Having at least one thrombophilia, mutation of factor V Leiden and homozygote form of MTHFR mutation were risk factors for recurrent IVF failure. PMID- 25114670 TI - Subclinical hypothyroidism and insulin resistance in polycystic ovary syndrome: is there a relationship? AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common hyperandrogenic disorder among women and is often defined as hyperandrogenic syndrome. These patients are at risk for oligo/amenorrhea, chronic anovulation, infertility, obesity, spontaneous abortion, insulin resistance, hyperinsulinemia and metabolic syndrome. Thyroid disorders especially hypothyroidism is more common in these people. In PCOS patients, subclinical hypothyroidism may aggravate insulin resistance. OBJECTIVE: The goal was to find any relationship between subclinical hypothyroidism and insulin resistance in PCOS patients. MATERIALS AND METHODS: In this prospective cross sectional study we included all PCOS patients coming to infertility clinic of Taleghani Hospital in 2010-2012 who had the criteria of Rotterdam for PCOS. Then the clinical examination was done for them and height, weight, body mass index and lab data were measured including thyroid hormone and biochemical profile. The data were analyzed by SPSS software version 20. RESULTS: Among 75 PCOS patients, 19 (25.5%) had subclinical hypothyroidism and 56 patients (74.4%) were euthyroid. The prevalence of insulin resistance was 22.7% and 77.3% of patients had no insulin resistance were normal. CONCLUSION: We could find no relationship between insulin resistance and subclinical hypothyroidism in PCOS patients. PMID- 25114669 TI - Emotional experiences in surrogate mothers: A qualitative study. AB - BACKGROUND: Surrogacy is one of the new techniques of assisted reproduction technology in which a woman carries and bears a child for another woman. In Iran, many Shia clerics and jurists considered it permissible so there is no religious prohibition for it. In addition to the risk of physical complications for complete surrogate mothers, the possibility of psychological complications resulted from emotional attachment to a living creature in the surrogate mother as another injury requires counseling and assessment prior to acceptance by infertile couples and complete surrogate mothers. OBJECTIVE: The purpose of this study was to assess the emotional experiences of surrogate mothers. MATERIALS AND METHODS: This was a qualitative, phenomenological study. We selected eight complete surrogate mothers in Isfahan. We used convenient sampling method and in depth interview to collect the information. The data analysis was fulfilled via Colaizzi's seven-stage method. Reliability and validity study of the roots in the four-axis was done. RESULTS: The findings of these interviews were classified into two main themes and four sub themes: acquired experiences in pregnancy (feelings toward pregnancy, relationship with family, relatives and commissioning couple) and consequences of surrogacy (complications of pregnancy, religious and financial problems of surrogacy). CONCLUSION: Surrogacy pregnancy should be considered as high-risk emotional experience because many of surrogate mothers may face negative experiences. Therefore, it is recommended that surrogates should receive professional counseling prior to, during and following pregnancy. PMID- 25114671 TI - Diagnostic value of gastric shake test for hyaline membrane disease in preterm infant. AB - BACKGROUND: Hyaline membrane disease (HMD) has remained a common neonatal problem and is a cause of morbidity in infants. The shake test can be used to assess whether surfactant is present in the infant's lungs at birth. OBJECTIVE: The goal of this study was to determine the usefulness and accuracy of gastric aspirate shake test for the diagnosis of two HMD. MATERIALS AND METHODS: This was a diagnostic accuracy study carried out on 49 preterm infant born at Shahid Sadoughi hospital in 2012 (25 newborns without pulmonary diseases and 24 newborns with HMD). Shortly after birth, the shake test was performed using gastric fluid. The results of the shake test were correlated with definitive diagnosis of HMD. RESULTS: All infants who developed HMD had negative test results. In 23 of 25 infants with no respiratory distress, the test was positive. Our findings indicated that the gastric aspirate shake test has 100% sensitivity, 92% specificity, a 92.3% predictive value for surfactant deficiency, and 100% predictive value for surfactant sufficiency. CONCLUSION: According to this study gastric shake test (GST) is a reliable test and is a simple procedure to identify those neonates who will develop respiratory distress syndrome (RDS) and therefore to decide prophylactic exogenous surfactant replacement. PMID- 25114672 TI - Ovarian stimulation medications and patients' responses as prognostic factors in IUI-treated infertile Saudi patients. AB - BACKGROUND: Intrauterine Insemination (IUI) remains the first thought of infertility treatment. OBJECTIVE: To compare the stimulation effects and Pregnancy rate (PR) outcomes of two ovulation induction (OI) medications, human derived menopausal gonadotrophins (hMGH), Merional (MER), and recombinant follicular stimulating hormone (rFSH), Puregon (PUR), in a cohort of Saudi infertile patients, for better predictability of treatment results. MATERIALS AND METHODS: During a 24-month period, 296 women underwent IUI single treatments. PR's were correlated with the type of stimulation medication that were prospectively and randomly assigned to each patient, and with the number and size of maturing follicles detected on the hCG injection day. RESULTS: MER and PUR needed comparable number of days (9.26+/-4.74 and 9.73+/-6.27 respectively) before follicles were ready for IUI, although the average amount used from MER, 1199.90 IU, was about double that was used from PUR, 621.08 IU. The overall PR in case of PUR however was nearly double that of MER, 13.28% and 7.14% respectively. The best PR, 16.22%, occurred when the follicles matured within 12-13 days. Three follicles of at least 15-mm diameter on the hCG day had better PR's than one or two, however when the follicles' diameters were at least 18-mm, PR was significantly higher, (p=0.013). CONCLUSION: MER and PUR had comparable stimulation effects; however PUR had noticeably higher PR. The best PR occurred when the follicles matured within 12-13 days. PR in case of three maturing follicles on the hCG day was better than only one or two, and significantly better when their diameters were at least 18 mm. PMID- 25114673 TI - INSR gene variation is associated with decreased insulin sensitivity in Iraqi women with PCOs. AB - BACKGROUND: Polycystic ovarian syndrome (PCOS) is a complex, heterogeneous disorder of uncertain etiology with strong genetic background. Insulin resistance is present in the majority of PCOS cases with linkage and association between single nucleotide polymorphisms of insulin receptor (INSR) gene and PCOS. OBJECTIVE: To examine whether the exon 17 of INSR gene contributes to genetic susceptibility to PCOS in Iraqi women and its effects on glucose tolerance test and lipid profile. MATERIALS AND METHODS: Sixty-five healthy Iraqi women and eighty-four infertile women with PCOS, divided into two subgroups depending on the BMI were studied. Restriction fragment length polymorphism (RFLP-PCR) analysis was performed to determine the genotypes for the His 1058 C/T polymorphism at the tyrosine kinase domain in the INSR gene. Clinical, anthropometric and biochemical parameters were also estimated. RESULTS: The C/T polymorphism at His 1058 in exon 17 of INSR was associated with PCOS (obese and non-obese). CC genotype frequency was higher in PCOS patients whereas TT genotype was higher in control women. Those with CC genotype had higher BMI, GTT and lipid profile than those with TT genotype. CONCLUSION: An association of C/T polymorphism at His1058 of INSR with PCOS in Iraqi women was observed. Its association with indices of insulin resistance and dyslipidemia were also noticed. PMID- 25114674 TI - Prevalence of Trichomonas vaginalis infection in Kashan city, Iran (2012-2013). AB - BACKGROUND: Trichomonas vaginalis infection is one of the most common sexually transmitted diseases in humans. T.vaginalis is a parasitic protozoan with a predilection for human urogenital tract and causative agent for vaginitis, cervicitis and urethritis in females. T.vaginalis infection is associated with risk of Human Immunodeficiency Virus infectivity and pregnancy complication. OBJECTIVE: In this study, the prevalence of T.vaginalis in individuals who referred to public health units in Kashan city, Iran was investigated. MATERIALS AND METHODS: This study was conducted on 970 women and 235 men who referred to 5 government health centers in Kashan, Iran during October 2012 to August 2013. Demographic information was collected as per the study protocol. Vaginal discharges and urine samples were obtained and examined by Trypticase-Yeast Extract Maltose (TYM) culture medium and wet-mount methods. The prevalence of T. vaginalis was determined using culture based method and wet-mount examinations. RESULTS: The overall prevalence of trichomonal infection was 2% (95% CI, 2+/ 0.08). The age of infected individual was 33.7+/-9.4 years. All of those infected, were married housewives and 58.3% of them had primary school education. No statistical correlation was observed between clinical manifestations and parasitological results (p=0.8). CONCLUSION: This study showed a relatively low prevalence of T.vaginalis infection in the study population. Since the clinical signs of trichomoniasis are the same of other Sexually Transmitted Diseases (STDs), confirmatory laboratory tests are necessary. Due to adverse outcomes of disease, there is a great need for public education regarding implementation of personal hygienic measures and prevention of inappropriate sexual contacts. PMID- 25114675 TI - Evaluation of clinical factors influencing pregnancy rate in frozen embryo transfer. AB - BACKGROUND: Frozen embryo transfer (FET) is one of the most important supplementary procedures in the treatment of infertile couples. While general information concerning the outcome of fresh embryo transfer has been documented, paucity of investigations has addressed the clinical factors influenced on pregnancy rates in FET. OBJECTIVE: In this study, we performed a retrospective analysis of clinical factors that potentially influence the outcome of FET. MATERIALS AND METHODS: We reviewed the data from 372 women who were subjected to FET registered from April 2009-2011 at the Research and clinical center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Baseline data and pregnancy rate were collected. The data were analyzed statistically using the Kolmogorov Smirnov, and Mann-Whitney tests. RESULTS: The clinical pregnancy rate was 57.7 and 29.2% in women <35 years old, and women >35 years old, respectively (p<0.0001). Clinical pregnancy rates in women with FSH <10 IU/ml, and FSH >10 IU/ml were 56.3% and 17.5 %, respectively (p<0.0001). Whereas the other clinical parameters consist of reason of fetus freezing, primary IVF protocol, IVF procedure, endometrial thickness, treatment duration to fetal transfer found to be unrelated to FET outcomes (p>0.05). CONCLUSION: Female age and basal FSH level are the most important factors influencing the clinical pregnancy rate following FET. PMID- 25114676 TI - Feature and score fusion based multiple classifier selection for iris recognition. AB - The aim of this work is to propose a new feature and score fusion based iris recognition approach where voting method on Multiple Classifier Selection technique has been applied. Four Discrete Hidden Markov Model classifiers output, that is, left iris based unimodal system, right iris based unimodal system, left right iris feature fusion based multimodal system, and left-right iris likelihood ratio score fusion based multimodal system, is combined using voting method to achieve the final recognition result. CASIA-IrisV4 database has been used to measure the performance of the proposed system with various dimensions. Experimental results show the versatility of the proposed system of four different classifiers with various dimensions. Finally, recognition accuracy of the proposed system has been compared with existing N hamming distance score fusion approach proposed by Ma et al., log-likelihood ratio score fusion approach proposed by Schmid et al., and single level feature fusion approach proposed by Hollingsworth et al. PMID- 25114677 TI - IL1RN and KRT13 Expression in Bladder Cancer: Association with Pathologic Characteristics and Smoking Status. AB - Purpose. To validate microarray data on cytokeratin 13 (KRT13) and interleukin-1 receptor antagonist (IL1RN) expression in urothelial carcinoma of the urinary bladder (UCB) and to correlate our findings with pathologic characteristics and tobacco smoking. Methods. UCB tissue samples (n = 109) and control samples (n = 14) were obtained from transurethral resection and radical cystectomy specimens. Immunohistochemical staining of KRT13 and IL1RN was performed and semiquantitative expression scores were assessed. Smoking status was evaluated using a standardized questionnaire. Expression scores were correlated with pathologic characteristics (tumor stage and grade) and with smoking status. Results. Loss of KRT13 and IL1RN expression was observed in UCB tissue samples when compared to controls (P = 0.007, P = 0.008) in which KRT13 and IL1RN expression were high. IL1RN expression was significantly reduced in muscle invasive tumors (P = 0.003). In tissue samples of current smokers, a significant downregulation of IL1RN was found when compared to never smokers (P = 0.013). Conclusion. Decreased expressions of KRT13 and IL1RN are common features of UCB and are associated with aggressive disease. Tobacco smoking may enhance the loss of IL1RN, indicating an overweight of proinflammatory mediators involved in UCB progression. Further validation of the influence of smoking on IL1RN expression is warranted. PMID- 25114678 TI - Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus. AB - The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP 1beta), dipeptidyl peptidase-IV (DPP-IV), aldose reductase (AR), and insulin receptor (IR) with help of docking software Molegro virtual docker (MVD). From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications. PMID- 25114679 TI - The Association between IGF-1 Polymorphisms, IGF-1 Serum Levels, and Cognitive Functions in Healthy Adults: The Amsterdam Growth and Health Longitudinal Study. AB - Several studies have demonstrated an association between polymorphisms in the insulin-like growth factor-1 (IGF-1) gene and IGF-1 serum levels. IGF-1 levels have been associated with cognitive functioning in older persons and growth hormone deficient patients. The present study investigates whether IGF-1 polymorphisms, IGF-1 levels, and cognition are interconnected in healthy adults. Data of 277 participants (mean age: 42.4 years) of the Amsterdam Growth and Health Longitudinal Study on IGF-1 promoter polymorphisms, IGF-1 serum level, spatial working memory (SWM), paired associate learning (PAL), and IQ tests were analyzed. (M)ANOVAs were applied to confirm the associations between IGF-1 polymorphisms and IGF-1 levels and between IGF-1 levels and cognition. Three groups were distinguished based on specific IGF-1 polymorphism alleles: a homozygote 192 bp/192 bp genotype, a heterozygote 192 bp/x genotype, and a noncarrier x/x genotype. Although different IGF-1 levels were found for the three genotypes, performance on all cognitive tasks and IQ measures was similar. Despite the associations between IGF-1 polymorphisms and IGF-1 levels, no association was found between cognition and IGF-1 levels. It seems that IGF-1 does not play a role in the cognitive performance of healthy middle-aged adults. Possible, IGF-1 fulfills a more developmental and protective role in cognition which becomes apparent during childhood, old-age, or disease. PMID- 25114681 TI - Response to initial therapy of differentiated thyroid cancer predicts the long term outcome better than classical risk stratification systems. AB - Objective. Although differentiated thyroid cancer (DTC) usually has an indolent course, some cases show a poor prognosis; therefore, risk stratification is required. The objective of this study is to compare the predictive ability of classical risk stratification systems proposed by the European Thyroid Association (ETA) and American Thyroid Association (ATA) with the system proposed by Tuttle et al. in 2010, based on the response to initial therapy (RIT). Methods. We retrospectively reviewed 176 cases of DTC with a median follow-up period of 7.0 years. Each patient was stratified using ETA, ATA, and RIT systems. Negative predictive value (NPV) and positive predictive value (PPV) were determined. The area under receiver operating characteristic (ROC) curve was calculated in order to compare the predictive ability. Results. RIT showed a NPV of 97.7%, better than NPV of ETA and ATA systems (93.9% and 94.9%, resp.). ETA and ATA systems showed poor PPV (40.3% and 41%, resp.), while RIT showed a PPV of 70.8%. The area under ROC curve was 0.7535 for ETA, 0.7876 for ATA, and 0.9112 for RIT, showing statistical significant differences (P < 0.05). Conclusions. RIT predicts the long-term outcome of DTC better than ETA/ATA systems, becoming a useful system to adapt management strategies. PMID- 25114680 TI - ATP Synthase beta-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level. AB - HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase beta-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase beta-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase beta-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of beta-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL HDL uptake in primary hepatocytes. In response to hepatic overexpression of beta chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase beta-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C. PMID- 25114682 TI - Body Mass Index Is Associated with Hypercholesterolemia following Thyroid Hormone Withdrawal in Thyroidectomized Patients. AB - Thyroid hormone withdrawal (THW) for postoperative radioiodine adjuvant therapy or diagnostic radioiodine whole body scan in patients with differentiated thyroid cancers results in acute thyroid hormone deficiency and abnormal lipid profiles. To better clarify the clinical pattern of dyslipidemia occurring after THW, we retrospectively analyzed the association between serum total cholesterol level after THW and various clinical factors in a total of 61 patients who underwent total thyroidectomy due to papillary thyroid cancers from January 2010 to March 2012, in Severance Hospital, Seoul, Korea. Preoperative baseline total cholesterol was significantly correlated with post-THW total cholesterol level; however, age, gender, or elevated TSH level after THW itself was not correlated with post-THW total cholesterol level. A significant correlation between preoperative measured BMI and post-THW total cholesterol level was found (r = 0.263, P = 0.041). In multiple logistic analysis, BMI was an independent determining factor of post-THW total cholesterol level (P = 0.012). PMID- 25114683 TI - Computer-based diagnostic expert systems in rheumatology: where do we stand in 2014? AB - Background. The early detection of rheumatic diseases and the treatment to target have become of utmost importance to control the disease and improve its prognosis. However, establishing a diagnosis in early stages is challenging as many diseases initially present with similar symptoms and signs. Expert systems are computer programs designed to support the human decision making and have been developed in almost every field of medicine. Methods. This review focuses on the developments in the field of rheumatology to give a comprehensive insight. Medline, Embase, and Cochrane Library were searched. Results. Reports of 25 expert systems with different design and field of application were found. The performance of 19 of the identified expert systems was evaluated. The proportion of correctly diagnosed cases was between 43.1 and 99.9%. Sensitivity and specificity ranged from 62 to 100 and 88 to 98%, respectively. Conclusions. Promising diagnostic expert systems with moderate to excellent performance were identified. The validation process was in general underappreciated. None of the systems, however, seemed to have succeeded in daily practice. This review identifies optimal characteristics to increase the survival rate of expert systems and may serve as valuable information for future developments in the field. PMID- 25114685 TI - Postpartum ovarian vein and inferior vena cava thrombosis. AB - Postpartum ovarian vein thrombosis (POVT), which generally occurs 2-15 days postpartum, is a rare complication. It can be confused with acute appendicitis, pelvic infection, ovarian torsion, tubo-ovarian abscess, and pyelonephritis. It is associated with morbidity and mortality. Here, we present a patient with postpartum OVT and IVC diagnosed by US and CT findings. She was treated successfully with no further need for any interventional procedures. PMID- 25114684 TI - HBV Reactivation in Patients Treated with Antitumor Necrosis Factor-Alpha (TNF alpha) Agents for Rheumatic and Dermatologic Conditions: A Systematic Review and Meta-Analysis. AB - Introduction. Antitumor necrosis factor-alpha (TNF-alpha) agents are widely used for treatment of rheumatic and dermatological diseases. We conducted the systematic review and meta-analysis to assess the prevalence of HBV reactivation among patients treated with anti-TNF-alpha. Methods and Findings. A comprehensive literature search of MEDLINE, Scopus, and ISI Web of Knowledge databases was conducted. From 21 studies included in the systematic review, 9 included patients with occult chronic HBV infection and 6 included patients with overt infection while 6 addressed both groups. Based on 10 studies eligible for meta-analysis we report pooled estimate of HBV reactivation of 4.2% (95% CI: 1.4-8.2%, I (2): 74.7%). The pooled prevalence of reactivation was 3.0% (95% CI: 0.6-7.2, I (2): 77.1%) for patients with occult infection, and 15.4% (95% CI: 1.2-41.2%, I (2): 79.9%) for overt infection. The prevalence of reactivation was 3.9% (95% CI: 1.1 8.4%, I (2): 51.1%) for treatment with etanercept and 4.6% (95% CI: 0.5-12.5%, I (2): 28.7%) for adalimumab. For subgroup of patients without any antiviral prophylaxis the pooled reactivation was 4.0% (95% CI: 1.2-8.3%, I (2): 75.6%). Conclusion. Although HBV reactivation rate is relatively low in patients treated with anti-TNF-alpha for rheumatic and dermatological conditions, the antiviral prophylaxis would be recommended in patients with overt chronic HBV infection. PMID- 25114687 TI - Giant solitary fibrous tumor of the parotid gland. AB - Solitary fibrous tumors (SFTs) are rare tumors that are mostly found arising from the pleura. SFT of the parotid gland is a rare tumor; only a few cases have been described in the literature. SFTs are benign in most cases. Clinically, SFTs usually manifest as well circumscribed, slow-growing, smooth, and painless masses. CT-Scan and MRI are the most sensitive imaging procedures used. The treatment of choice is complete surgical excision of the lesion. Since recurrence and metastasis can take place after several years, a lifelong clinical and imaging regular follow-up is compulsory. In this paper, we describe the diagnostic and therapeutic challenges of the up-to-now biggest parotid SFT. The clinical presentation, surgical management, and pathological and immunohistochemistry findings are described. PMID- 25114686 TI - Wolff-Parkinson-white syndrome mimics a conduction disease. AB - Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a "false positive" of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope. PMID- 25114688 TI - Clinical presentation and magnetic resonance findings in sellar tuberculomas. AB - Background and Importance. Sellar tuberculomas are extremely rare lesions with nonspecific clinical manifestations. The tuberculous infection of the pituitary gland and sellar region is characterized by the presence of an acute or chronic inflammatory reaction and may occur in the absence of systemic tuberculosis. The diagnosis is difficult prior to the surgery. An adequate diagnostic and antituberculous drugs usually result in a good outcome. Clinical Presentation. We report four cases of sellar tuberculoma, 3/1 female/male, age range: 50-57 years. All patients had visual disturbances and low levels of cortisol. Conclusion. The clinical diagnosis of sellar tuberculoma is a challenge and should be suspected when a sellar lesion shows abnormal enhancement pattern and stalk involvement, and absence of signal suppression in FLAIR. PMID- 25114689 TI - Comprehensive understanding of atrial septal defects by imaging studies for successful transcatheter closure. AB - Transcatheter closure of atrial septal defects has become a popular procedure. The availability of a preprocedural imaging study is crucial for a safe and successful closure. Both the anatomy and morphology of the defect should be precisely evaluated before the procedure. Three-dimensional (3D) echocardiography and cardiac computed tomography are helpful for understanding the morphology of a defect, which is important because different defect morphologies could variously impact the results. During the procedure, real-time 3D echocardiography can be used to guide an accurate closure. The safety and efficiency of transcatheter closures of atrial septal defects could be improved through the use of detailed imaging studies. PMID- 25114691 TI - Prader-Willi syndrome: a single center's experience in Korea. AB - PURPOSE: Prader-Willi syndrome (PWS) is a complex genetic disorder that results from the lack of paternally expressed genes in the chromosome 15q11-q13 region. This study was performed to delineate the clinical features of PWS infants and toddlers and the effects of two-year growth hormone (GH) treatment according to gender and age at the start of treatment. METHODS: The clinical characteristics and the results of the GH treatment were reviewed retrospectively for 30 PWS patients diagnosed by molecular genetic testing and clinical manifestations. RESULTS: The mean age at diagnosis with PWS was 13.7 months (2-47 months of age). All patients showed the characteristics of facial dysmorphism, including brown hair and almond-shaped eyes. Most patients showed developmental delays/mental retardation (93.3%), cryptorchidism (75%), feeding problems in infancy (73.3%), and neonatal or infantile hypotonia (66.7%). Among 30 patients, 14 PWS infants and toddlers had been treated with GH for more than two years. Two years of GH treatment resulted in an improvement in head circumference-standard deviation score (HC-SDS), body weight-SDS, insulin-like growth factor-1 (IGF-1) SDS, IGF binding protein-3 (IGFBP-3) SDS, lean body mass, and bone mineral content, especially in IGFBP-3 SDS and motor development in PWS patients younger than two years of age. There was significant increase in IGF-1 SDS and IGFBP-3 SDS among male PWS patients after GH treatment. CONCLUSION: Our study showed increases in IGFBP-3 SDS and an improvement in motor development among individuals under two years of age after GH treatment, and significant difference in IGF-1 SDS and IGFBP-3 SDS by gender. PMID- 25114690 TI - Benign convulsion with mild gastroenteritis. AB - Benign convulsion with mild gastroenteritis (CwG) is a type of afebrile seizure that occurs in children. CwG is defined as a convulsion in a previously healthy child with no known central nervous system infection or encephalopathy, accompanying mild diarrhea without fever, electrolyte imbalance, or moderate to severe dehydration. Convulsions in CwG are characterized by multiple brief episodes of generalized or focal seizures. Although the etiology and pathophysiology have yet to be fully explained, many pathogenic mechanisms have been proposed including the possibility of direct invasion of the central nervous system by a gastrointestinal virus such as rotavirus or the possibility of indirect influence by the production and effects of certain mediators. The electroencephalogram findings are benign and long-term antiepileptic treatment is typically not required. Long-term prognosis has been favorable with normal psychomotor development. This review provides a general overview of CwG with the goal of allowing physicians practicing in the field of pediatrics to better recognize this unique entity and, ultimately, to minimize unnecessary evaluation and treatment. PMID- 25114692 TI - Prevalence of restless legs syndrome and sleep problems in Korean children and adolescents with attention deficit hyperactivity disorder: a single institution study. AB - PURPOSE: Attention deficit hyperactivity disorder (ADHD) is a common disorder in school-aged children. Patients with restless legs syndrome (RLS) often present with ADHD symptoms and vice versa. This study was the first to attempt to identify the prevalence of RLS and sleep problems in children with ADHD in Korea. METHODS: Patients diagnosed with ADHD were asked to complete a sleep questionnaire. The sleep questionnaire included items to help identify the presence of four typical symptoms that are used as diagnostic criteria for RLS. RESULTS: A total of 56 patients, including 51 boys and 5 girls (mean age, 10.7 years old) participated. Of these, 24 complained of pain, discomfort, or an unpleasant sensation in the legs. Based on the RLS diagnostic criteria, 2 patients were diagnosed with definite RLS and 4 with probable RLS. There were no significant differences in age, medication dosage, or neuropsychological test scores between the patients with and without RLS symptoms. CONCLUSION: Approximately 42.9% of patients with ADHD presented with RLS symptoms and 7.1% of these were diagnosed with RLS. Patients with ADHD also experienced various other sleep disorders. Thus, appropriate assessment and treatment for sleep disorders in patients with ADHD is essential. PMID- 25114693 TI - Articulation error of children with adenoid hypertrophy. AB - PURPOSE: Adenoid hypertrophy is a physical alteration that may affect speech, and a speech disorder can have other negative effects on a child's life. Airway obstruction leads to constricted oral breathing and causes postural alterations of several oro-facial structures, including the mouth, tongue, and hyoid bone. The postural modifications may affect several aspects of speech production. METHODS: In this study, we compared articulation errors in 19 children with adenoid hypertrophy (subject group) to those of 33 children with functional articulation disorders independent of anatomical problems (control group). RESULTS: The mean age of the subject group was significantly higher (P=0.016). Substitution was more frequent in the subject group (P=0.003; odds ratio [OR], 1.80; 95% confidence interval [CI], 1.23-2.62), while omission was less frequent (P<0.001; OR, 0.43; 95% CI, 0.27-0.67). Articulation errors were significantly less frequent in the palatal affricative in the subject group (P=0.047; OR, 0.25; 95% CI, 0.07-0.92). The number of articulation errors in other consonants was not different between the two groups. Nasalization and aspiration were significantly more frequent in the subject group (P=0.007 and 0.014; OR, 14.77 and 0.014; 95% CI, [1.62-135.04] and NA, respectively). Otherwise, there were no differences between the two groups. CONCLUSION: We identified the characteristics of articulation errors in children with adenoid hypertrophy, but our data did not show the relationship between adenoid hypertrophy and oral motor function that has been observed in previous studies. The association between adenoid hypertrophy and oral motor function remains doubtful. PMID- 25114694 TI - Asymptomatic maternal 3-methylcrotonylglycinuria detected by her unaffected baby's neonatal screening test. AB - 3-methylcrotonyl-coenzyme A carboxylase (3MCC) deficiency is an autosomal recessive disorder in which leucine catabolism is hampered, leading to increased urinary excretion of 3-methylcrotonylglycine. In addition, 3 hydroxyisovalerylcarnitine levels increase in the blood, and the elevated levels form the basis of neonatal screening. 3MCC deficiency symptoms are variable, ranging from neonatal onset with severe neurological abnormality to a normal, asymptomatic phenotype. Although 3MCC deficiency was previously considered to be rare, it has been found to be one of the most common metabolic disorders in newborns after the neonatal screening test using tandem mass spectrometry was introduced. Additionally, asymptomatic 3MCC deficient mothers have been identified due to abnormal results of unaffected baby's neonatal screening test. Some of the 3MCC-deficient mothers show symptoms such as fatigue, myopathy, or metabolic crisis with febrile illnesses. In the current study, we identified an asymptomatic 3MCC deficient mother when she showed abnormal results during a neonatal screening test of a healthy infant. PMID- 25114695 TI - Atypical teratoid rhabdoid brain tumor in an infant with ring chromosome 22. AB - Reports of constitutional ring chromosome 22, r(22) are rare. Individuals with r(22) present similar features as those with the 22q13 deletion syndrome. The instability in the ring chromosome contributes to the development of variable phenotypes. Central nervous system (CNS) atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant tumors, primarily occurring in young children below 3 years of age. The majority of ATRT cases display genetic alterations of SMARCB1 (INI1/hSNF5), a tumor suppressor gene located on 22q11.2. The coexistence of a CNS ATRT in a child with a r(22) is rare. We present a case of a 4-month-old boy with 46,XY,r(22)(p13q13.3), generalized hypotonia and delayed development. High-resolution microarray analysis revealed a 3.5-Mb deletion at 22q13.31q13.33. At 11 months, the patient had an ATRT (5.6 cm*5.0 cm*7.6 cm) in the cerebellar vermis, which was detected in the brain via magnetic resonance imaging. PMID- 25114696 TI - Diagnosis of pulmonary tuberculosis and nontuberculous mycobacterial lung disease in Korea. AB - The recovery of nontuberculous mycobacteria (NTM) from respiratory specimens and the number of patients with NTM lung disease have been rapidly increasing in Korea. An early differential diagnosis of NTM lung disease from pulmonary tuberculosis (TB) is important, as the therapeutic regimen differs from that of pulmonary TB, and it is not necessary to track the contacts of patients with NTM lung disease. However, differentiating NTM lung disease from pulmonary TB remains difficult, because the clinical presentations of the two diseases are similar and a definite diagnosis of NTM lung disease based on sputum culture takes time. This review focuses on the changing epidemiology, clinical and radiographic manifestation, and laboratory diagnosis of pulmonary TB and NTM lung disease in Korea. PMID- 25114697 TI - Clinical year in review 2014: critical care medicine. AB - Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units. In 2002, the guideline titled "Surviving Sepsis Campaign" was published by American and European Critical Care Medicine to decrease the mortality of severe sepsis and septic shock patients, which has been the basis of the treatment for those patients. After the first revised guidelines were published on 2008, the most current version was published in 2013 based on the updated literature of until fall 2012. Other important revised guidelines in critical care field such as 'Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit' were revised in 2013. This article will review the revised guidelines and several additional interesting published papers of until March 2014, including the part of ventilator-induced lung injury and the preventive strategies. PMID- 25114698 TI - Outcomes of second-line chemotherapy for advanced non-small cell lung cancer in one institution. AB - BACKGROUND: This study analyzed the negative prognostic factors in patients who received second-line chemotherapy for advanced inoperable non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed the records of 137 patients with inoperable stage III-IV NSCLC who received second-line chemotherapy. The effects of clinical parameters on survival were analyzed and the hazard ratios (HR) for mortality were identified by a Cox regression analysis. RESULTS: Sex, age older than 65 years, smoking history, cell type, T-stage, best response to first-line chemotherapy and first-line chemotherapy regimen were significant negative predictors in univariate analysis. The multivariate analysis showed that patients older than 65 years (HR, 1.530; 95% confidence interval [CI], 1.020 2.297), advanced T stage (T4 vs. T1; HR, 2.273; 95% CI, 1.010-5.114) and non responders who showed progression with first-line chemotherapy (HR, 1.530; 95% CI, 1.063-2.203) had higher HR for death. CONCLUSION: The age factor, T stage and responsiveness to first-line chemotherapy were important factors in predicting the outcome of patients with advanced NSCLC who received second-line chemotherapy. The results may help to predict outcomes for these patients in the future. PMID- 25114699 TI - Annual Change in Pulmonary Function and Clinical Characteristics of Combined Pulmonary Fibrosis and Emphysema and Idiopathic Pulmonary Fibrosis: Over a 3-Year Follow-up. AB - BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) have different pulmonary function tests (PFTs) and outcomes than idiopathic pulmonary fibrosis (IPF). The intention of this study was to identify unknown differences between CPFE and IPF by a retrospective comparison of clinical data including baseline and annual changes in pulmonary function, comorbidities, laboratory findings, clinical characteristics and cause of hospitalization. METHODS: This study retrospectively enrolled patients with CPFE and IPF who had undergone PFTs once or several times per year during a follow-up period of three years. Baseline clinical characteristics and the annual changes in the pulmonary function during the follow-up period were compared between 26 with CPFE and 42 patients with IPF. RESULTS: The baseline ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC%) in patients with CPFE was lower than that in patients with IPF (78.6+/-1.7 vs. 82.9+/-1.1, p=0.041). The annual decrease in FEV1/FVC in the CPFE was significantly higher than in the IPF. The annual decreases in diffusion capacity of carbon monoxide and FVC showed no significant differences between the two groups. The symptom durations of cough and sputum were in the CPFE significantly lower than in the IPF. The serum erythrocyte sedimentation rate level at the acute stage was significantly higher than in the IPF. There were no significant differences in the hospitalization rate and pneumonia was the most common cause of hospitalization in both study groups. CONCLUSION: The annual decrease of FEV1/FVC was in patients with CPFE significantly higher than in the patients with IPF. PMID- 25114700 TI - Takotsubo cardiomyopathy caused by pulmonary tuberculosis: a case report. AB - Takotsubo cardiomyopathy (TTC) is defined as a reversible, acute ventricular dysfunction without any evidence of coronary artery obstruction. There have been reports of TTC caused by emotional or physical stress, drug use, hormone imbalance, or medical conditions such as pulmonary disease, sepsis, and trauma, but a relationship between TTC and pulmonary tuberculosis has not previously been reported. From our knowledge, this is the first report of TTC caused by pulmonary tuberculosis. PMID- 25114701 TI - A case of invasive pulmonary aspergillosis with direct invasion of the mediastinum and the left atrium in an immunocompetent patient. AB - We report a case of invasive pulmonary aspergillosis invading the mediastinum and the left atrium. A 70-year-old woman was hospitalized for dyspnea. She had been well controlled for her diabetes mellitus and hypertension. The chest X-ray disclosed mediastinal widening, and the computed tomography scan of the chest showed that there was a large mediastinal mass and this lesion extended into the left atrium and right bronchus. The cardiac echocardiography showed that a huge mediastinal cystic mass compressed in the right atrium and a hyperechoic polypoid lesion in the left. The pathology from the bronchoscopic biopsy observed abundant fungal hyphae which was stained with periodic acid-Schiff and Gomori's methenamine silver. Despite the treatment with antifungal agents, she died from cardiac tamponade after three months. Invasive pulmonary aspergillosis, which involves the mediastinum and the heart, is very rare in immunocompetent patients. PMID- 25114702 TI - Multiple hypercoagulability disorders at presentation of non-small-cell lung cancer. AB - Hypercoagulability disorders are commonly encountered in clinical situations in patients with a variety of cancers. However, several hypercoagulability disorders presenting as first symptoms or signs in cancer patients have rarely been reported. We herein described a case of a woman with adenocarcinoma of the lung presenting with deep vein thrombosis, nonbacterial thrombotic endocarditis, recurrent cerebral embolic infarction, and heart failure. PMID- 25114703 TI - A case of lung carcinoma with rhabdoid phenotype mimicking an aspergilloma in patient with recurrent hemoptysis. AB - Malignant rhabdoid tumor was first discovered in the kidney, and rhabdoid tumor of the lung was first reported in 1995. These were included as the variants of large-cell carcinoma, according to the 1999 World Health Organization classification of lung tumors. The rhabdoid tumor of the lung exhibits aggressive biological behavior and has a poor prognosis, and only a few reports of this tumor exist. We report a case of lung carcinoma with a rhabdoid phenotype, initially misdiagnosed as an aspergilloma, in a 48-year-old man who presented with recurrent hemoptysis. The chest computed tomography scans showed a huge consolidative lesion with an air crescent sign in the left upper lung and no contrast-enhancing lesion. An aspergilloma was diagnosed by the radiologist. However, after surgical excision and pathological examination, rhabdoid carcinoma was diagnosed. A surgical resection helps to make it possible to pathologically distinguish a malignancy from an aspergilloma. PMID- 25114705 TI - Analgesia Synergism of Essential Oil from Pericarp of Zanthoxylum schinifolium and Verapamil. AB - Objective. To evaluate the synergistic analgesic effect of essential oil of Zanthoxylum schinifolium Sieb. et Zucc. (EOZ) and verapamil (Ver). Method. The qualitative and quantitative composition of EOZ were determined with gas chromatography/Mass spectrometer. The interaction between EOZ and Ver in antinociceptive activity was evaluated by using acetic acid-induced writhing, hot plate, and tail flick tests in mice and in isolated toad sciatic nerve test. Results. Linalool, limonene, and sabinene are the major components of EOZ. EOZ (middle-dose: 40 mg.kg(-1), high-dose: 80 mg.kg(-1)) and EOZ + Ver (Each dose group) have remarkable analgesic effects on pain in mice induced by acetic acid induced writhing, hot plate, and tail flick tests. Low-dose EOZ (20 mg.kg(-1)) had no analgesic action, but when it is combined with Ver it has shown significant antinociception. Verapamil has a faint analgesic effect but was not able to inhibit action potential transmission in toad sciatic nerve. EOZ (0.2%) and EOZ + Ver (0.2% + 0.05%) also inhibited action potential transmission in toad sciatic nerve. Combination of EOZ with Ver had a greater analgesic effect and inhibition of nerve action potential transmission compared to its components EOZ and Ver. Conclusion. The combination of EOZ with Ver produces a synergistic analgesic effect. PMID- 25114704 TI - Miniscalpel-Needle versus Steroid Injection for Plantar Fasciitis: A Randomized Controlled Trial with a 12-Month Follow-Up. AB - Plantar fasciitis is the most common cause of heel pain in adults. A novel alternative medical instrument, the miniscalpel-needle (MSN), which is based on an acupuncture needle, has been recently developed in China. The objective of this study was to evaluate the effectiveness of the MSN release treatment versus that of traditional steroid injection for plantar fasciitis. Patients with plantar fasciitis were randomly assigned to 2 groups and followed up for 12 months, with 29 receiving MSN treatment and 25 receiving steroid injection treatment. The results showed that visual analog scale scores for morning pain, active pain, and overall heel pain all were decreased significantly in the MSN group from 1 to 12 months after treatment. In contrast, treatment with steroid injection showed a significant effect only at the 1-month follow-up but not at 6 or 12 months after treatment. Moreover, the MSN group achieved more rapid and sustained improvements than the steroid group throughout the duration of this study. No severe side effects were observed with MSN treatment. Our data suggest that the MSN release treatment is safe and has a significant benefit for plantar fasciitis compared to steroid injection. PMID- 25114706 TI - The Comparative Study on Expression of SIRT1 Signal Transduction by Xuefuzhuyu Capsule. AB - The Xuefuzhuyu capsule (XFZY) is widely used for the treatment of ischemic heart disease (IHD) in China. We previously demonstrated that XFZY could reduce apoptosis in Sprague-Dawley rat cardiomyocytes with the similar effect of resveratrol (Res) Hori et al. (2013), although its molecular mechanism underlying this protective effect is still unclear. Silent information regulator of transcription 1 (SIRT1) had been demonstrated to be responsible for cardioprotection against ischemia-reperfusion injury via long-term transcriptionally regulatory mechanism Braunersreuther and Jaquet (2012). Therefore, in the present study, we aimed to test if XFZY might contribute to the protection of ischemic myocardial cells induced by ischemia through SIRT1 mediated signal transduction pathway by using electron micrograph, RT-PCR assay, and western-blot test. All the result showed that the target genes of SIRT1 pathway including P53, NF-kB, FOXO1, FOXO3, and FOXO4 were significantly downregulated to SIRT1, suggesting that apoptosis pathway might transcriptionally be regulated to SIRT1. In addition, the expression level of SIRT1 was significantly increased by XFZ, it might prove that SIRT1 is the target of XFZY working on ischemia heart disease. Our findings supported that XFZY might function to protect myocardial cells and reduce myocardial injury though SIRT1 signaling pathway and has the same pharmacological effect with Res. PMID- 25114707 TI - Acupuncture and depth: future direction for acupuncture research. AB - The research on acupuncture has increased steadily over the years and regular review and revision of the direction of future acupuncture research are necessary. This paper aims to review and explore the significance of acupuncture depth in modern acupuncture research. Searches conducted in Science Direct and China National Knowledge Infrastructure (CNKI) databases reflected a lack of focus on depth of acupuncture. We propose that the research trends of acupuncture should progress to the depth of insertion. It is suggested that future acupuncture research, especially randomized controlled trials (RCTs), should take into consideration the depth of insertion. Comparison between databases using different language of medium suggests the need for international collaboration of researchers from the same field. It is also crucial to inherit and innovate traditional medicine (TM) through modern technology. The use of bibliometric method is also suitable for development of TM research trends. Acupuncture and depth should be considered as one of the future directions of acupuncture research. PMID- 25114708 TI - Identification of chinese herbal medicines from zingiberaceae family using feature extraction and cascade classifier based on response signals from e-nose. AB - Identification of Chinese herbal medicines (CHMs) by human experience is often inaccurate because individual ability and external factors may influence the outcome. However, it might be promising to employ an electronic nose (E-nose) to identify them. This paper presents a rapid and reliable method for identification of ten different species of CHMs from Zingiberaceae family based on their response signals from E-nose. Ten Zingiberaceae CHMs were measured and their maximum response values were analyzed by principal component analysis (PCA). Result shows that E Zhu (Curcuma phaeocaulis Val.) and Yi Zhi (Alpinia oxyphylla Miq.) could not be distinguished completely by PCA. Two solutions were proposed: (i) using BestFirst+CfsSubsetEval (BC) method to extract more discriminative features to select sensors with higher contribution rate and remove the redundant signals; (ii) employing a novel cascade classifier with two stages to enhance the distinguishing-positive rate (DPR). Based on these strategies, six features were extracted and used in different stages of the cascade classifier with higher DPRs. PMID- 25114709 TI - Effects of young barley leaf powder on gastrointestinal functions in rats and its efficacy-related physicochemical properties. AB - Young barley leaf is consumed as a popular green-colored drink, which is named "Aojiru" in Japan. In the present study, we examined effects of young barley leaf powder (BL) on gastrointestinal transit time (GTT) and fecal moisture and weight in comparison with wheat bran (WB) in male Sprague-Dawley rats. In addition, an attempt was made to identify BL components responsible for these effects by using various fractions of BL. Additionally, we examined the water-holding capacity and setting volume of BL in vitro. We also examined the granular structures of BL with a scanning electron microscope. As a result, BL supplementation in the diet increased the fecal weight and shortened GTT. Our results demonstrate that the active component responsible for the effect on increasing the fecal volume in BL is the water-insoluble dietary fiber fraction and that this effect is thought to be caused by stimulation of the gut tract by the pH lowering. Furthermore, the high laxative action of BL was thought to be ascribable to the high water-holding capacity due to the complicated structures of BL. PMID- 25114710 TI - Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle. AB - BACKGROUND: Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain. METHODS: C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro. RESULTS: Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid beta oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1alpha expression in the skeletal muscle. CONCLUSIONS: Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders. PMID- 25114711 TI - Three-graded stratification of carbohydrate restriction by level of baseline hemoglobin A1c for type 2 diabetes patients with a moderate low-carbohydrate diet. AB - BACKGROUND: A moderate low-carbohydrate diet has been receiving attention in the dietary management of type 2 diabetes (T2DM). A fundamental issue has still to be addressed; how much carbohydrate delta-reduction (Deltacarbohydrate) from baseline would be necessary to achieve a certain decrease in hemoglobin A1c (HbA1c) levels. OBJECTIVE: We investigated the effects of three-graded stratification of carbohydrate restriction by patient baseline HbA1c levels on glycemic control and effects of Deltacarbohydrate on decreases in HbA1c levels (DeltaHbA1c) in each group. RESEARCH DESIGN AND METHODS: We treated 122 outpatients with T2DM by three-graded carbohydrate restriction according to baseline HbA1c levels (<= 7.4% for Group 1, 7.5%-8.9% for Group 2 and >= 9.0% for Group 3) and assessed their HbA1c levels, doses of anti-diabetic drugs and macronutrient intakes over 6 months. RESULTS: At baseline, the mean HbA1c level and carbohydrate intake were 6.9 +/- 0.4% and 252 +/- 59 g/day for Group 1 (n = 55), 8.1 +/- 0.4% and 282 +/- 85 g/day for Group 2 (n = 41) and 10.6 +/- 1.4% and 309 +/- 88 g/day for Group 3 (n = 26). Following three-graded carbohydrate restriction for 6 months significantly decreased mean carbohydrate intake (g/day) and HbA1c levels for all patients, from 274 +/- 78 to 168 +/- 52 g and from 8.1 +/- 1.6 to 7.1 +/- 0.9% (n = 122, P < 0.001 for both) and anti-diabetic drugs could be tapered. DeltaHbA1c and Deltacarbohydrate were -0.4 +/- 0.4% and -74 +/- 69 g/day for Group 1, -0.6 +/- 0.9% and -117 +/- 78 g/day for Group 2 and -3.1 +/ 1.4% and -156 +/- 74 g/day for Group 3. Linear regression analysis showed that the greater the carbohydrate intake, the greater the HbA1c levels at baseline (P = 0.001). Also, the greater the reduction in carbohydrate intake (g/day), the greater the decrease in HbA1c levels (P < 0.001), but DeltaHbA1c was not significantly influenced by changes in other macronutrient intakes (g/day). CONCLUSIONS: Three-graded stratification of carbohydrate restriction according to baseline HbA1c levels may provide T2DM patients with optimal objectives for carbohydrate restriction and prevent restriction from being unnecessarily strict. PMID- 25114712 TI - A novel cost effective and high-throughput isolation and identification method for marine microalgae. AB - BACKGROUND: Marine microalgae are of major ecologic and emerging economic importance. Biotechnological screening schemes of microalgae for specific traits and laboratory experiments to advance our knowledge on algal biology and evolution strongly benefit from culture collections reflecting a maximum of the natural inter- and intraspecific diversity. However, standard procedures for strain isolation and identification, namely DNA extraction, purification, amplification, sequencing and taxonomic identification still include considerable constraints increasing the time required to establish new cultures. RESULTS: In this study, we report a cost effective and high-throughput isolation and identification method for marine microalgae. The throughput was increased by applying strain isolation on plates and taxonomic identification by direct PCR (dPCR) of phylogenetic marker genes in combination with a novel sequencing electropherogram based screening method to assess the taxonomic diversity and identity of the isolated cultures. For validation of the effectiveness of this approach, we isolated and identified a range of unialgal cultures from natural phytoplankton communities sampled in the Arctic Ocean. These cultures include the isolate of a novel marine Chlorophyceae strain among several different diatoms. CONCLUSIONS: We provide an efficient and effective approach leading from natural phytoplankton communities to isolated and taxonomically identified algal strains in only a few weeks. Validated with sensitive Arctic phytoplankton, this approach overcomes the constraints of standard molecular characterisation and establishment of unialgal cultures. PMID- 25114713 TI - Predicting tooth surface loss using genetic algorithms-optimized artificial neural networks. AB - Our aim was to predict tooth surface loss in individuals without the need to conduct clinical examinations. Artificial neural networks (ANNs) were used to construct a mathematical model. Input data consisted of age, smoker status, type of tooth brush, brushing, and consumption of pickled food, fizzy drinks, orange, apple, lemon, and dried seeds. Output data were the sum of tooth surface loss scores for selected teeth. The optimized constructed ANN consisted of 2-layer network with 15 neurons in the first layer and one neuron in the second layer. The data of 46 subjects were used to build the model, while the data of 15 subjects were used to test the model. Accepting an error of +/-5 scores for all chosen teeth, the accuracy of the network becomes more than 80%. In conclusion, this study shows that modeling tooth surface loss using ANNs is possible and can be achieved with a high degree of accuracy. PMID- 25114714 TI - RNA-RNA interaction prediction using genetic algorithm. AB - BACKGROUND: RNA-RNA interaction plays an important role in the regulation of gene expression and cell development. In this process, an RNA molecule prohibits the translation of another RNA molecule by establishing stable interactions with it. In the RNA-RNA interaction prediction problem, two RNA sequences are given as inputs and the goal is to find the optimal secondary structure of two RNAs and between them. Some different algorithms have been proposed to predict RNA-RNA interaction structure. However, most of them suffer from high computational time. RESULTS: In this paper, we introduce a novel genetic algorithm called GRNAs to predict the RNA-RNA interaction. The proposed algorithm is performed on some standard datasets with appropriate accuracy and lower time complexity in comparison to the other state-of-the-art algorithms. In the proposed algorithm, each individual is a secondary structure of two interacting RNAs. The minimum free energy is considered as a fitness function for each individual. In each generation, the algorithm is converged to find the optimal secondary structure (minimum free energy structure) of two interacting RNAs by using crossover and mutation operations. CONCLUSIONS: This algorithm is properly employed for joint secondary structure prediction. The results achieved on a set of known interacting RNA pairs are compared with the other related algorithms and the effectiveness and validity of the proposed algorithm have been demonstrated. It has been shown that time complexity of the algorithm in each iteration is as efficient as the other approaches. PMID- 25114716 TI - How can a change in the operating system of the mental health review board promote the discharge of long-term hospitalized psychiatric patients? A case study of Seoul city. AB - BACKGROUND: One of the most typical and chronic problem in Korean mental health system is the prolonged length of hospital stay. In contrast to there are many components which leads to long length of stay of psychiatric patients in Korean situation such as low and fixed medical fee for psychiatric inpatient treatment, shortage of community resources, lack of care-givers' awareness and so on, there are just few mechanisms to handle this issue such as Mental Health Review Board (MHRB) which is based on Mental Health Act since 1995. However, the discharge order rate was very low and there community care system after discharge order is still very weak. CASE DESCRIPTION: The Korean government has revised the Mental Health Act in 2008 and changed the operating principals of the MHRB from a regional level to a local level to strengthen the function of MHRB. However, the discharge order rate versus the whole evaluation requests still remains at a very low level or less than 5%. And it is still very difficult to execute a discharge order against a patient whose symptoms and conditions become psychiatrically stabilized enough for discharge, due to a shortage of community care facilities and a lack of social support system. These results are exactly same with former studies. DISCUSSION: Any policies to promote psychiatric discharge including MHRB are needed to take the comprehensive factors into consideration, such as payment program, community infrastructure, increasing care-givers' acceptance and so on. CONCLUSION: Despite of the political trial of Korean government to reduce length of stay of chronic psychiatric patients, it was not successful. Still it had failed to propose a detailed policy measure in terms of the above-mentioned prerequisites. Therefore, new system and program developments including reform of payment system which reflect prior studies' recommendations are essential. PMID- 25114717 TI - Clinical and epidemiological profile of cases of deaths from stomach cancer in the National Cancer Institute, Brazil. AB - INTRODUCTION: Stomach cancer is the third most common cause of death worldwide, mainly affecting people with low socioeconomic status. In Brazil, we expect 20,390 new cases of stomach cancer in 2014, in both sexes, and according to the proportional distribution of the ten most prevalent types of cancer (except non melanoma skin cancer) expected for 2014, this type of cancer was estimated to be the fourth most common in men and sixth in women. AIM: To investigate and analyse the clinical and epidemiological profile of deaths caused by stomach adenocarcinoma in patients enrolled in the National Cancer Institute, Brazil. METHODS: Cross-sectional study, with samples which consisted of data from the medical records of deaths from stomach cancer, enrolled in the period from 1 February 2009 to 31 March 2012 and who had died as of 30 April 2012. STATISTICAL ANALYSIS USED: The Epi Info (r), version 7. RESULTS: We included 264 cases, mostly male. The mean age was 61.7 years. They were smokers, drinkers, white, and married, with elementary education and an income of one minimum salary. They had advanced stage disease (E IV), with symptoms characteristic of this phase, and the majority died within six months. CONCLUSION: The findings are similar to other studies. The advanced stage of the disease at the time of admission of the patients reflects the difficulty for users of the Unified Health System to access early diagnosis, demonstrating the need for efforts to identify groups and risk factors for the development of gastric cancer. Training of health professionals will facilitate planning and implementation of programmes for the prevention and control of disease, considering socioeconomic conditions, as seen in the sample, which is common among most users. PMID- 25114718 TI - Sympathetic nervous system alterations with HER2+ antagonism: an early marker of cardiac dysfunction with breast cancer treatment? AB - BACKGROUND: HER2 antagonists (anti-HER2; e.g., trastuzumab and lapatinib) are effective in treating an aggressive form of breast cancer (BC), but can cause cardiotoxicity due to the disruption in neuregulin (NRG)/HER2+ ligand receptor signalling. The recent data show that NRG-HER2 receptors located in the medulla oblongata are important regulators of vasomotor tone. Disrupting the NRG-HER2 signalling in mouse medulla results in increased sympathetic nerve output and blood pressure. We hypothesized that anti-HER2 agents would cause increased sympathetic tone with changes in plasma catecholamines and NRG. METHODS: In 15 newly diagnosed HER2+ BC patients receiving anti-HER2 agents, vital signs were measured along with supine plasma epinephrine (EPI), norepinephrine (NE), and NRG at baseline and three months. Serial echocardiography was performed. RESULTS: With three months of anti-HER2 treatment, NE increased (2.334 +/- 1.294 nmol/L vs. 3.262 +/- 2.103 nmol/L; p = 0.004) and NRG decreased (12.7+/-15.7 ng/ml vs. 10.9 +/- 13.3 ng/ml; p = 0.036) with a corresponding increase in systolic blood pressure (110 +/- 10 mmHg vs. 120 +/- 16 mmHg, p = 0.049) and diastolic blood pressure (67 +/- 14 vs. 77 +/- 10, p = 0.009). There was no change, however, in EPI (0.183 +/- 0.151 nmol/L vs. 0.159 +/- 0.174 nmol/L; p = 0.519) or heart rate (73 +/- 12 bpm vs. 77 +/- 10 bpm, p = 0.146). Left ventricular ejection function declined over the follow-up period (baseline 63 +/- 6% vs. follow-up 56 +/- 5%). CONCLUSIONS: Anti-HER2 treatment results in increased NE, blood pressure, and decreased NRG; this suggests that the inhibition of NRGHER2 signalling leads to increased sympathoneural tone. Larger studies are needed to determine if these observations have prognostic value and may be offset with medical interventions, such as beta-blockers. CLINICAL TRIAL REGISTRATION: The study was registered with www.clinicaltrials.gov (NCT00875238). PMID- 25114715 TI - Diagnosis and treatment of perforated or bleeding peptic ulcers: 2013 WSES position paper. PMID- 25114719 TI - Spindle cell carcinoma of the tongue: a rare variant of squamous cell carcinoma. AB - Spindle cell carcinoma (SpCC), a rare, aggressive variant of squamous cell carcinoma (SCC), is characterised by proliferation of epithelial and mesenchymal components. It is important to diagnose this variant of SCC, because of its tendency to recur and early metastasis. It accounts for 1% of all tumours in the oral cavity. In this paper, we have reported a case of SpCC of the tongue in a 65 year-old male who presented with a polypoidal growth over the lateral border of his tongue with a short history of one month. Immunohistochemical expression of cytokeratin was strongly positive in the epithelial component and focally in the spindle cell component. The spindle cell component showed a strong positivity for vimentin. PMID- 25114720 TI - Clinicopathologic subtypes and compromise of lymph nodes in patients with breast cancer. AB - Breast cancer (BC) is currently a heterogeneous disease with variations in clinical behaviour. Classification according to subtypes has allowed progress in the individualisation of treatment. The objective of this study is to evaluate the risk of axillary node compromise in patients with BC, according to clinicopathologic subtypes. Materials and methods are a retrospective, descriptive-analytical study. All patients that had undergone surgery for invasive BC were included, with the study of sentinel lymph nodes (SLNs) at Hospital Clinico de la Pontificia Universidad Catolica, between May 1999 and December 2012. The results showed 632 patients fulfilled the inclusion criteria, with the median age being 55 years (range: 28-95), and 559 (88.4%) patients presented with estrogen receptor and/or progesterone receptor positive tumours. Luminal A: 246 patients (38.9%), luminal B: 243 (38.4%), luminal not otherwise specified: 70 (11.1%) triple negative (TN): 60 (9.5%) and over expression of epidermal growth factor type 2 receptor (HER2 positive): 13 (2.1%). Luminal tumours displayed a greater risk of metastasis in the SLNs, but this difference was not statistically significant (p = 0.67). TN and HER2 positive tumours presented the greatest proportion of metastatic compromise in non-sentinel lymph nodes (non-SLNs) (57.1% and 50%, respectively). The presence of macrometastasis (MAM) in the SLN was associated with a greater risk of compromise of the non-SLN. CONCLUSIONS: Luminal tumours are the most frequent and present a greater proportion of axillary lymph node compromise, without being statistically significant. TN and HER2 positive tumours tend to have a higher axillary compromise; however, this was not statistically significant in either. Only the presence of MAM in SLNs displayed a statistically significantly association in the compromise of non-SLNs. PMID- 25114721 TI - Anaplastic thyroid cancer: multimodal treatment results. AB - BACKGROUND: Anaplastic thyroid cancer is a rare and lethal disease. It accounts for 1-2% of thyroid malignancies, but specific mortality is higher than 90%. It is an aggressive locoregional disease with a high metastatic capacity. There is no agreement with regards to the best treatment. We analysed the results of treatment in a mestizo population treated in the National Cancer Institute (Mexico). METHODS: We reviewed 1,581 files of thyroid carcinomas; of these, 29 (1.83%) had anaplastic thyroid carcinoma. Demographic variables, clinical manifestations, tumour characteristics, and treatments were analysed. RESULTS: The median age was 64.5 +/- 13.2 years. Females were more affected (female/male ratio: 2.6:1); 21 cases occurred in women (72.4%), and eight in males (27.6%). The most common manifestations were neck enlargement (93.10%) and hoarseness (71.31%). The median tumour size was 8 cm (range: 4-20 cm). The percentage of cases which presented in clinical stage IVA was 10.3%, with 62.1% presenting in clinical stage IVb and 27.6% presenting in clinical stage VIc. Complete resection (R0) (p = 0.05), radiation doses of higher than 33.1 Gy (p = 0.04), and multimodal therapy were associated with better survival. Surgery plus radiotherapy with or without systemic treatment (p = 0.006). The median overall survival was 119 days (IC 95%, 36.3-201.6). Six-month, one-year and two-year survival was 37.9%, 21% and 13%, respectively. CONCLUSION: Complete surgical resection is associated with better survival but is very difficult to achieve due to aggressive biological behaviour. Multimodal therapy is associated with better survival and a better quality of life. There is a need for more effective systemic treatments as extensive surgical resections have little overall benefit in highly invasive and metastatic disease. PMID- 25114723 TI - NHS reforms in England: the implications for chemotherapy commissioning. AB - For oncology, one of the biggest effects of the reforms to the National Health Service (NHS) in England has been the designation of systemic anticancer treatments (other than hormonal agents) as a specialised service. This means that all decisions regarding the commissioning of chemotherapy are made at the national level via NHS England (NHSE), under expert guidance from the Chemotherapy Clinical Reference Group (CRG). Commissioning decisions will be based on several factors, not only clinical efficacy and cost/affordability, but also the 'added value' that a new treatment may offer in terms of patient outcomes, resource utilisation, and/or wider benefits to society. Oncology health care professionals (HCPs) are in a position to affect cancer commissioning decisions in the reformed NHS, not only the small number who are members of the Chemotherapy CRG, but also as advisors to the Chemotherapy CRG via disease specific consensus work, and through participation in the collection and reporting of real-life data on patient outcomes. With the emerging emphasis on both consensus work and outcomes data, a step change can also be expected in the relationship between HCPs and the pharmaceutical industry, including a strengthened role for non-promotional education, support for forums and consensus groups, and facilitation of the development, collection, and dissemination of findings from real-life practice. In addition, there will be an onus on the pharmaceutical industry to provide information on the implications that new products may have for service delivery and capacity and for meeting patients' and society's expectations. This information will need to be developed and delivered in a timely way, well in advance of the launch of a new product. PMID- 25114724 TI - Watching as an ordinary affect: Care and mothers' preemption of injury in child supervision. AB - As unintentional injuries continue to be the leading cause of hospitalization and death for toddlers between the ages of 1 and 4, the Centers for Disease Control has argued that child supervision is a key factor in reducing these injuries and fatalities. This article focuses on the affective relationships in the concept of supervision and practice of watching as an injury prevention method. Three parts frame our argument. First, we describe how watching is an ordinary affect. Second, as part of the ethos of caring, watching is embedded in a temporal frame of anticipation and gives rise to an affectsphere of watching and to a parents' subjectivity as 'good' or 'bad' supervisors. Third, these affective relationships generate seemingly contradictory outcomes wherein children are expected to gain independence and experience injury. The affective qualities of watching provide a critique of the individualizing forces of supervision and an analysis of subjectivities generated by gender and class. PMID- 25114722 TI - Neuroendocrine carcinoma of the cervix presenting as intractable hyponatremic seizures due to paraneoplastic SIADH-a rare case report and brief review of the literature. AB - Herein is presented an interesting case of small-cell neuroendocrine carcinoma of the cervix which initially manifests as seizures due to hyponatremia caused by paraneoplastic syndrome of inappropriate anti diuretic hormone (SIADH). Awareness of a paraneoplastic syndrome at presentation can lead to early diagnosis and early initiation of treatment. The management is also unique in that it combines treating the paraneoplastic aspects as well as targeting the tumour itself. Multimodality treatment gives the best outcome in this aggressive tumour. PMID- 25114725 TI - Use of diagnostic imaging in the evaluation of gastrointestinal tract duplications. AB - BACKGROUND: Gastrointestinal tract duplication is a rare malformation associated with the presence of additional segment of the fetal gut. The aim of this study was to retrospectively review clinical features and imaging findings in intraoperatively confirmed cases of gastrointestinal tract duplication in children. MATERIAL/METHODS: The analysis included own material from the years 2002-2012. The analyzed group included 14 children, among them 8 boys and 6 girls. The youngest patient was diagnosed at the age of three weeks, and the oldest at 12 years of age. RESULTS: The duplication cysts were identified in the esophagus (n=2), stomach (n=5), duodenum (n=1), terminal ileum (n=5), and rectum (n=1). In four cases, the duplication coexisted with other anomalies, such as patent urachus, Meckel's diverticulum, mesenteric cyst, and accessory pancreas. Clinical manifestation of gastrointestinal duplication cysts was variable, and some of them were detected accidently. Thin- or thick-walled cystic structures adjacent to the wall of neighboring gastrointestinal segment were documented on diagnostic imaging. CONCLUSIONS: Ultrasound and computed tomography are the methods of choice in the evaluation of gastrointestinal duplication cysts. Apart from the diagnosis of the duplication cyst, an important issue is the detection of concomitant developmental pathologies, including pancreatic heterotopy. PMID- 25114726 TI - Effect of a short time concentric versus eccentric training program on electromyography activity and peak torque of quadriceps. AB - The purpose of this study was to examine the effect of an 8-week concentric (CON) versus eccentric (ECC) isokinetic training program on the electromyography (EMG) signal amplitude of vastus medialis (VM), vastus lateralis (VL) and rectus femoris (RF). Also, the isometric (ISO) and dynamic maximum strength of the knee extensors were assessed. Eighteen physically healthy male subjects (age 22 +/- 1 years, body height 177 +/- 4 cm, body mass 73 +/- 7 kg) performed four weeks of unilateral CON isokinetic training for the quadriceps of the dominant leg on a REV9000 dynamometer. At the end of the fourth week, the sample was divided into two groups, with one group performing additional four weeks of unilateral ECC training and the other continuing with CON training. The training sessions consisted of three sets of ten maximal repetitions at a velocity of 60os-1, three days per week for eight weeks. The results showed that CON and ECC groups improved the peak torque in all types of contractions. Also, both groups presented increases in the avgEMG for VL, VM and RF. The present investigation showed that CON training elicited increases of the ISO peak torque and VM avgEMG in the CON contraction. Additionally, significant gains were reported after the ECC training on the VM avgEMG in all contractions and RM avgEMG in CON contraction. PMID- 25114727 TI - Lower Extremity Muscle Activity During a Women's Overhand Lacrosse Shot. AB - The purpose of this study was to describe lower extremity muscle activity during the lacrosse shot. Participants (n=5 females, age 22+/-2 years, body height 162.6+/-15.2 cm, body mass 63.7+/-23.6 kg) were free from injury and had at least one year of lacrosse experience. The lead leg was instrumented with electromyography (EMG) leads to measure muscle activity of the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and medial gastrocnemius (GA). Participants completed five trials of a warm-up speed shot (Slow) and a game speed shot (Fast). Video analysis was used to identify the discrete events defining specific movement phases. Full-wave rectified data were averaged per muscle per phase (Crank Back Minor, Crank Back Major, Stick Acceleration, Stick Deceleration). Average EMG per muscle was analyzed using a 4 (Phase) * 2 (Speed) ANOVA. BF was greater during Fast vs. Slow for all phases (p<0.05), while TA was not influenced by either Phase or Speed (p>0.05). RF and GA were each influenced by the interaction of Phase and Speed (p<0.05) with GA being greater during Fast vs. Slow shots during all phases and RF greater during Crank Back Minor and Major as well as Stick Deceleration (p<0.05) but only tended to be greater during Stick Acceleration (p=0.076) for Fast vs. Slow. The greater muscle activity (BF, RF, GA) during Fast vs. Slow shots may have been related to a faster approach speed and/or need to create a stiff lower extremity to allow for faster upper extremity movements. PMID- 25114728 TI - Neuromuscular responses of elite skaters during different roller figure skating jumps. AB - This study aimed to describe the neuromuscular activity of elite athletes who performed various roller figure skating jumps, to determine whether the muscle activation is greater during jumps with more rotations and in which phase the muscles are more active. This study also aimed to analyze if there is any difference in the muscle activity pattern between female and male skaters. Four elite skaters were evaluated, and each participated in two experimental sessions. During the first session, anthropometric data were collected, and the consent forms were signed. For the second session, neuromuscular data were collected during jumps, which were performed with skates at a rink. The following four roller figure skating jumps were evaluated: single Axel, double Axel, double Mapes and triple Mapes. The neuromuscular activity of the following seven muscles was obtained with an electromyograph which was fixed to the waist of each skater with a strap: biceps femoris, lateral gastrocnemius, tibialis anterior, rectus femoris, vastus lateralis, vastus medialis and gluteus maximus. The signal was transmitted wirelessly to a laptop. During the roller figure skating jumps, the lateral gastrocnemius, rectus femoris, vastus lateralis, biceps femoris and gluteus maximus, showed more activation during the jumps with more rotations, and the activation mainly occurred during the propulsion and flight phases. Female skaters demonstrated higher muscle activities in tibialis anterior, vastus lateralis, vastus medialis and gluteus maximus during the landing phase of the triple Mapes, when compared to their male counterparts. The results obtained in this study should be considered when planning training programs with specific exercises that closely resemble the roller figure skating jumps. This may be important for the success of elite skaters in competitions. PMID- 25114729 TI - Comparison of static balance and the role of vision in elite athletes. AB - When prescribing balance exercises to athletes in different sports, it may be important to recognize performance variations. Indeed, how athletes from different sports perform on balance tests is not well understood. The goal of the present study was to compare static balance and the role of vision among elite sprinters, jumpers and rugby players. The modified clinical test of sensory interaction on balance (mCTSIB) was used to assess the velocity of the center-of pressure (CoP) on a force platform during a 30 s bipedal quiet standing posture in 4 conditions: firm surface with opened and closed eyes, foam surface with opened and closed eyes. Three-factor ANOVA indicated a significant main effect for groups (F=21.69, df=2, p<0.001, eta(2) = 0.34). Significant main effect of vision (F=43.20, df=1, p<0.001, eta(2) = 0.34) and surface (F=193.41, df=1, p<0.001, eta(2) = 0.70) as well as an interaction between vision (eyes open, eyes closed) and surface (firm and foam) (F=21.79, df=1, p=0.001) were reported in all groups. The subsequent Bonferroni-Dunn post hoc test indicated that rugby players displayed better static balance than sprinters and jumpers (p=0.001). The comparison of sprinters and jumpers did not reveal significant differences (p>0.05). The nature of the sport practiced and the absence of visual control are linked to modify static balance in elite athletes. Coaches and strength and conditioning professionals are recommended to use a variety of exercises to improve balance, including both exercises with opened and closed eyes on progressively challenging surfaces in order to make decisions about tasks and sensory availability during assessment and training. PMID- 25114730 TI - Effect of training mode on post-exercise heart rate recovery of trained cyclists. AB - The sympathetic nervous system dominates the regulation of body functions during exercise. Therefore after exercise, the sympathetic nervous system withdraws and the parasympathetic nervous system helps the body return to a resting state. In the examination of this relationship, the purpose of this study was to compare recovery heart rates (HR) of anaerobically versus aerobically trained cyclists. With all values given as means +/- SD, anaerobically trained track cyclists (n=10, age=25.9 +/- 6.0 yrs, body mass=82.7 +/- 7.1 kg, body fat=10.0 +/- 6.3%) and aerobically trained road cyclists (n=15, age=39.9 +/- 8.5 yrs, body mass=75.3 +/- 9.9 kg, body fat=13.1 +/- 4.5%) underwent a maximal oxygen uptake test. Heart rate recovery was examined on a relative basis using heart rate reserve as well as the absolute difference between maximum HR and each of two recovery HRs. The post-exercise change in HR at minute one for the track cyclists and road cyclists respectively were 22 +/- 8 bpm and 25 +/- 12 bpm. At minute two, the mean drop for track cyclists was significantly (p<0.05) greater than the road cyclists (52 +/- 15 bpm and 64 +/- 11 bpm). Training mode showed statistically significant effects on the speed of heart rate recovery in trained cyclists. Greater variability in recovery heart rate at minute two versus minute one suggests that the heart rate should be monitored longer than one minute of recovery for a better analysis of post-exercise autonomic shift. PMID- 25114731 TI - The kinematic control during the backward gait and knee proprioception: insights from lesions of the anterior cruciate ligament. AB - An already existing large volume of work on kinematics documents a reduction of step length during unusual gaits, such as backward walking. This is mainly explained in terms of modifications of some biomechanical properties. In the present study, we propose that the proprioceptive information from the knee may be involved in this change of motor strategy. Specifically, we show that a non automated condition such as backward walking can elicit different motor strategies in subjects with reduced proprioceptive feedback after anterior cruciate ligament lesion (ACL). For this purpose, the kinematic parameters during forward and backward walking in subjects with ACL deficit were compared to two control groups: a group with intact ACL and a group with surgically reconstructed ACL. The knee proprioception was tested measuring the threshold for detection of passive knee motion. Subjects were asked to walk on a level treadmill at five different velocities (1-5km/h) in forward and backward direction, thereby calculating the cadence and step length. Results showed that forward walking parameters were largely unaffected in subjects with ACL damage. However, they failed to reduce step length during backward walking, a correction that was normally observed in all control subjects and in subjects with normal proprioceptive feedback after ACL reconstruction. The main result of the present study is that knee proprioception is an important signal used by the brain to reduce step length during the backward gait. This can have a significant impact on clinical evaluation and rehabilitation. PMID- 25114732 TI - Effectiveness of Selected Fitness Exercises on Stress of Femoral Neck using Musculoskeletal Dynamics Simulations and Finite Element Model. AB - The purpose of the study was to establish a dynamics model and a three dimensional (3D) finite element model to analyze loading characteristics of femoral neck during walking, squat, single-leg standing, and forward and lateral lunges. One male volunteer performed three trials of the five movements. The 3D kinematic data were captured and imported into the LifeMOD to establish a musculoskeletal dynamics model to obtain joint reaction and muscle forces of iliacus, gluteus medius, gluteus maximus, psoas major and adductor magnus. The loading data LfeMOD were imported and transformed into a hip finite-element model. The results of the finite element femur model showed that stress was localized along the compression arc and the tension arc. In addition, the trabecular bone and tension lines of the Ward's triangle also demonstrated high stress. The compact bone received the greatest peak stress in the forward lunge and the least stress in the squat. However, the spongy bone in the femoral neck region had the greatest stress during the walk and the least stress in the squat. The results from this study indicate that the forward lunge may be an effective method to prevent femoral neck fractures. Walking is another effective and simple method that may improve bone mass of the Ward's triangle and prevent osteoporosis and femoral neck fracture. PMID- 25114733 TI - Effects of regular physical exercises in the water on the metabolic profile of women with abdominal obesity. AB - Recreational physical exercise in the water is predominantly based on aerobic metabolism. Since it involves both carbohydrate and lipid sources of energy, aqua aerobics has a beneficial effect on metabolism of these substrates. The aim of the study was to assess the impact of a 3 month aqua aerobics training program on the metabolic profile of women with abdominal obesity. The study sample comprised 32 women aged 41-72 years. Somatic characteristics and variables characterizing carbohydrate and lipid metabolism were measured before the commencement and after the completion of the training program. During the 2nd measurement all mean anthropometric variables were found to be significantly lower (p<=0.01). In the blood lipid profile, the concentrations of total cholesterol, LDL-cholesterol and HOMAIR were significantly lower (p<0.01). Furthermore, the levels of fasting triglycerides, glucose and insulin were reduced significantly (p<=0.05) after the training program. The aqua aerobics program contributed to positive changes in lipid metabolism, anthropometric variables, as well as the fasting insulin, glucose levels and insulin resistance index in women with abdominal obesity. PMID- 25114734 TI - Multi-Stage 20-m Shuttle Run Fitness Test, Maximal Oxygen Uptake and Velocity at Maximal Oxygen Uptake. AB - The multi-stage 20-m shuttle run fitness test (20mMSFT) is a popular field test which is widely used to measure aerobic fitness by predicting maximum oxygen uptake (VO2max) and performance. However, the velocity at which VO2max occurs (vVO2max) is a better indicator of performance than VO2max, and can be used to explain inter-individual differences in performance that VO2max cannot. It has been reported as a better predictor for running performance and it can be used to monitor athletes' training for predicting optimal training intensity. This study investigated the validity and suitability of predicting VO2max and vVO2max of adult subjects on the basis of the performance of the 20mMST. Forty eight (25 male and 23 female) physical education students performed, in random order, a laboratory based continuous horizontal treadmill test to determine VO2max, vVO2max and a 20mMST, with an interval of 3 days between each test. The results revealed significant correlations between the number of shuttles in the 20mMSFT and directly determined VO2max (r = 0.87, p<0.05) and vVO2max (r = 0.93, p<0.05). The equation for prediction of VO2max was y = 0.0276x + 27.504, whereas for vVO2max it was y = 0.0937x + 6.890. It can be concluded that the 20mMSFT can accurately predict VO2max and vVO2max and this field test can provide useful information regarding aerobic fitness of adults. The predicted vVO2max can be used in monitoring athletes, especially in determining optimal training intensity. PMID- 25114735 TI - The effect of a single session of whole-body vibration training in recreationally active men on the excitability of the central and peripheral nervous system. AB - Vibration training has become a popular method used in professional sports and recreation. In this study, we examined the effect of whole-body vibration training on the central nervous system and muscle excitability in a group of 28 active men. Subjects were assigned randomly to one of two experimental groups with different variables of vibrations. The chronaximetry method was used to evaluate the effect of a single session of whole-body vibration training on the excitability of the rectus femoris and brachioradialis muscles. The examination of the fusing and flickering frequencies of the light stimulus was performed. An increase in the excitability of the quadriceps femoris muscle due to low intensity vibrations (20 Hz frequency, 2 mm amplitude) was noted, and a return to the initial values was observed 30 min after the application of vibration. High intensity vibrations (60 Hz frequency, 4 mm amplitude) caused elongations of the chronaxy time; however, these differences were not statistically significant. Neither a low intensity vibration amplitude of 2 mm (frequency of 20 Hz) nor a high intensity vibration amplitude of 4 mm (frequency of 60 Hz) caused a change in the excitability of the central nervous system, as revealed by the average frequency of the fusing and flickering of the light stimulus. A single session of high intensity whole-body vibration did not significantly decrease the excitability of the peripheral nervous system while the central nervous system did not seem to be affected. PMID- 25114736 TI - Insights into Supplements with Tribulus Terrestris used by Athletes. AB - Herbal and nutritional supplements are more and more popular in the western population. One of them is an extract of an exotic plant, named Tribulus terrestris (TT). TT is a component of several supplements that are available over the-counter and widely recommended, generally as enhancers of human vitality. TT is touted as a testosterone booster and remedy for impaired erectile function; therefore, it is targeted at physically active men, including male athletes. Based on the scientific literature describing the results of clinical trials, this review attempted to verify information on marketing TT with particular reference to the needs of athletes. It was found that there are few reliable data on the usefulness of TT in competitive sport. In humans, a TT extract used alone without additional components does not improve androgenic status or physical performance among athletes. The results of a few studies have showed that the combination of TT with other pharmacological components increases testosterone levels, but it was not discovered which components of the mixture contributed to that effect. TT contains several organic compounds including alkaloids and steroidal glycosides, of which pharmacological action in humans is not completely explained. One anti-doping study reported an incident with a TT supplement contaminated by a banned steroid. Toxicological studies regarding TT have been carried out on animals only, however, one accidental poisoning of a man was described. The Australian Institute of Sport does not recommend athletes' usage of TT. So far, the published data concerning TT do not provide strong evidence for either usefulness or safe usage in sport. PMID- 25114737 TI - Changes in urinary 8-hydroxydeoxyguanosine levels during heptathlon race in professional female athletes. AB - Acute strenuous exercise can induce a state of oxidative stress affecting the involved muscles. Heptathlon is a multi-event exercise of two days duration and can be considered an acute, intensive endurance exercise. The purpose of this study is to compare the oxidative stress response to heptathlon events day by day and to determine the impact of this type of exercise on oxidative stress biomarkers. The study subjects included eight heptathlon athletes who participated in the National First Class Republic competition in Egypt (October 19-21, 2011). Blood samples were collected at rest after exercise for two successive days and analyzed for malondialdehyde (MDA). Morning urine samples were collected one hour after exercise for each day and were analyzed for 8 hydroxydeoxyguanosine (8-OHdG). Results revealed a significant increase (p<0.05) in both plasma MDA and urine 8-OHdG levels after exercise regardless of the day. We concluded that exercise generates higher MDA levels compared to DNA strand breaks and oxidative DNA damage in athletes with antioxidant supplementation. PMID- 25114738 TI - Effect of number of touches and exercise duration on the kinematic profile and heart rate response during small-sided games in soccer. AB - This study aimed to examine the effect of exercise duration and the number of touches allowed during possession on time-motion characteristics and the physiological responses of soccer players in 6 vs. 6 small-sided games (SSGs) lasting 12 minutes. The analysis divided each game into two 6-min periods and we compared two formats: free play (SSGFP) vs. a maximum of two touches per individual possession (SSG2T). Participants were 12 semi-professional players (age: 22.7+/-4.3 years; body height: 177.5+/-4.9 cm; body mass: 74.9+/-6.3 kg) and the following variables were measured by means of heart rate monitors and GPS devices: mean heart rate (HRmean), time spent in each exercise intensity zone, total distance covered, total distance covered in different speed zones, number of accelerations at different intensities, maximum speed reached, player load, and the work-to-rest ratio. The results showed that in SSGFP there was a decrease in the intensity of physical parameters during the second 6-min period (6-12 min), whereas this decrease was not observed when a maximum of two touches per individual possession was allowed. During the second period (6-12 min) of SSG2T there was an increase in HRmean and in the time spent in high exercise intensity zones, but these differences were not observed in SSGFP. The value of these findings for soccer coaches is that they illustrate how different technical, tactical or conditioning objectives could be addressed by altering the length and format of the SSG used in training. PMID- 25114739 TI - Effects of Strength Training Combined with Specific Plyometric exercises on body composition, vertical jump height and lower limb strength development in elite male handball players: a case study. AB - The purpose of the present study was to identify the effects of a strength training program combined with specific plyometric exercises on body composition, vertical jump (VJ) height and strength development of lower limbs in elite male handball players. A 12-week program with combined strength and specific plyometric exercises was carried out for 7 weeks. Twelve elite male handball players (age: 21.6 +/- 1.73) competing in the Portuguese Major League participated in the study. Besides the anthropometric measurements, several standardized jump tests were applied to assess VJ performance together with the strength development of the lower limbs in an isokinetic setting. No significant changes were found in body circumferences and diameters. Body fat content and fat mass decreased by 16.4 and 15.7% respectively, while lean body mass increased by 2.1%. Despite small significance, there was in fact an increase in squat jump (SJ), counter movement jump (CMJ) and 40 consecutive jumps after the training period (6.1, 3.8 and 6.8%, respectively). After the applied protocol, peak torque increased in lower limb extension and flexion in the majority of the movements assessed at 90os-1. Consequently, it is possible to conclude that combining general strength-training with plyometric exercises can not only increase lower limb strength and improve VJ performance but also reduce body fat content. PMID- 25114740 TI - Prediction of rowing ergometer performance from functional anaerobic power, strength and anthropometric components. AB - The aim of this research was to develop different regression models to predict 2000 m rowing ergometer performance with the use of anthropometric, anaerobic and strength variables and to determine how precisely the prediction models constituted by different variables predict performance, when conducted together in the same equation or individually. 38 male collegiate rowers (20.17 +/- 1.22 years) participated in this study. Anthropometric, strength, 2000 m maximal rowing ergometer and rowing anaerobic power tests were applied. Multiple linear regression procedures were employed in SPSS 16 to constitute five different regression formulas using a different group of variables. The reliability of the regression models was expressed by R2 and the standard error of estimate (SEE). Relationships of all parameters with performance were investigated through Pearson correlation coefficients. The prediction model using a combination of anaerobic, strength and anthropometric variables was found to be the most reliable equation to predict 2000 m rowing ergometer performance (R2 = 0.92, SEE= 3.11 s). Besides, the equation that used rowing anaerobic and strength test results also provided a reliable prediction (R2 = 0.85, SEE= 4.27 s). As a conclusion, it seems clear that physiological determinants which are affected by anaerobic energy pathways should also get involved in the processes and models used for performance prediction and talent identification in rowing. PMID- 25114741 TI - The impact of immediate verbal feedback on the improvement of swimming technique. AB - The present research attempts to ascertain the impact of immediate verbal feedback (IVF) on modifications of stroke length (SL). In all swimming styles, stroke length is considered an essential kinematic parameter of the swimming cycle. It is important for swimming mechanics and energetics. If SL shortens while the stroke rate (SR) remains unchanged or decreases, the temporal-spatial structure of swimming is considered erroneous. It results in a lower swimming velocity. Our research included 64 subjects, who were divided into two groups: the experimental - E (n=32) and the control - C (n=32) groups. A pretest and a post-test were conducted. The subjects swam the front crawl over the test distance of 25m at Vmax. Only the E group subjects were provided with IVF aiming to increase their SL. All tests were filmed by two cameras (50 samples*s-1). The kinematic parameters of the swimming cycle were analyzed using the SIMI Reality Motion Systems 2D software (SIMI Reality Motion Systems 2D GmbH, Germany). The movement analysis allowed to determine the average horizontal swimming velocity over 15 meters. The repeated measures analysis of variance ANOVA with a post-hoc Tukey range test demonstrated statistically significant (p<0.05) differences between the two groups in terms of SL and swimming velocity. IVF brought about a 6.93% (Simi method) and a 5.09% (Hay method) increase in SL, as well as a 2.92% increase in swimming velocity. PMID- 25114742 TI - Reliability of tethered swimming evaluation in age group swimmers. AB - The aim of the present study was to examine the reliability of tethered swimming in the evaluation of age group swimmers. The sample was composed of 8 male national level swimmers with at least 4 years of experience in competitive swimming. Each swimmer performed two 30 second maximal intensity tethered swimming tests, on separate days. Individual force-time curves were registered to assess maximum force, mean force and the mean impulse of force. Both consistency and reliability were very strong, with Cronbach's Alpha values ranging from 0.970 to 0.995. All the applied metrics presented a very high agreement between tests, with the mean impulse of force presenting the highest. These results indicate that tethered swimming can be used to evaluate age group swimmers. Furthermore, better comprehension of the swimmers ability to effectively exert force in the water can be obtained using the impulse of force. PMID- 25114744 TI - Game-Related Volleyball Skills that Influence Victory. AB - The aim of the present study was to identify the volleyball skills that discriminate in favour of victory. Twenty-four games (n=24) from the Senior Men's Volleyball World Championship played in Italy in 2010 were chosen and analyzed with Data Volley software. The discriminating function was used to identify the discriminating variables, using a canonical structuring coefficient of |SC| >= .30. The results suggest that service points, reception errors, and blocking errors were the discriminating variables that identify the final outcome of the match (victory/defeat). Moreover, successful service points were the major variable most likely associated with match success (victory). In this sense, increasing the effectiveness of service should be a top priority in coaching elite volleyball teams. PMID- 25114743 TI - Effects of high-intensity blood flow restriction exercise on muscle fatigue. AB - Strength training combined with blood flow restriction (BFR) have been used to improve the levels of muscle adaptation. The aim of this paper was to investigate the acute effect of high intensity squats with and without blood flow restriction on muscular fatigue levels. Twelve athletes (aged 25.95 +/- 0.84 years) were randomized into two groups: without Blood Flow Restriction (NFR, n = 6) and With Blood Flow Restriction (WFR, n = 6) that performed a series of free weight squats with 80% 1-RM until concentric failure. The strength of the quadriceps extensors was assessed in a maximum voluntary isometric contraction integrated to signals from the surface electromyogram. The average frequency showed significant reductions in the WFR group for the vastus lateralis and vastus medialis muscles, and intergroup only for the vastus medialis. In conclusion, a set of squats at high intensity with BFR could compromise muscle strength immediately after exercise, however, differences were not significant between groups. PMID- 25114745 TI - The reliability of a functional agility test for water polo. AB - Few functional agility tests for water polo take into consideration its specific characteristics. The preliminary objective of this study was to evaluate the reliability of an agility test for water polo players. Fifteen players (16.3 +/- 1.8 years old) with a minimum of two years of competitive experience were evaluated. A Functional Test for Agility Performance (FTAP) was designed to represent the context of this sport. Several trials were performed to familiarize the athlete with the movement. Two experienced coaches measured three repetitions of the FTAP. Descriptive statistics, repeated measures analysis of variance (ANOVA), 95% limit of agreement (LOA), intraclass correlation coefficient (ICC) and standard error of measurements (SEM) were used for data analysis. It was considered that certain criteria of reliability measures were met. There was no significant difference between the repetitions, which may be explained by an effect of the evaluator, the ability of the players or fatigue (p > 0.05). The ICC average from evaluators was high (0.88). The SEM varied between 0.13 s and 0.49 s. The CV average considering each individual was near 6-7%. These values depended on the condition of measurement. As the FTAP contains some characteristics that create a degree of unpredictability, the same athlete may reach different performance results, increasing variability. An adjustment in the sample, familiarization and careful selection of subjects help to improve this situation and enhance the reliability of the indicators. PMID- 25114746 TI - Comparing Tactical Behaviour of Soccer Players in 3 vs. 3 and 6 vs. 6 Small-Sided Games. AB - The present study aimed to compare players' tactical behaviour in 3 vs. 3 and 6 vs. 6 soccer small-sided games (SSGs). The sample comprised 3,482 tactical actions performed by 18 U-11 youth soccer players from a Portuguese club, in 3 vs. 3 and 6 vs. 6 SSGs. All participants played eight minutes in both situations and field size was adapted according to the number of players involved (30 m * 19.5 m for 3 vs. 3 and 60 m * 39 m for 6 vs. 6). The System of Tactical Assessment in Soccer (FUT-SAT) was used for data collection and analyses. Descriptive analysis was conducted to verify frequencies and percentages of the variables assessed. The chi-squared (chi(2)) test was performed to compare the frequencies of the variables between 3 vs. 3 and 6 vs. 6 SSGs and Standardized Residuals (e) were used to examine the influence of the frequency of one or more variables within 3 vs. 3 and 6 vs. 6 SSGs. Data treatment was performed through SPSS for Windows(r), version 18.0. Results indicated that players displayed safer behaviours in 6 vs. 6 SSG and more aggressive behaviours in 3 vs. 3 SSG. Findings can aid coaches and teachers to develop different players' tactical skills according to the chosen SSG (3 vs. 3 or 6 vs. 6) form. PMID- 25114747 TI - Effects of Match Location, Match Status and Quality of Opposition on Regaining Possession in UEFA Champions League. AB - The present study aimed to examine the independent and interactive effects of match location, match status, and quality of opposition on regaining possession, analysed by the type and zone of ball recovery, in matches played in the 2011 2012 UEFA Champions League. Twenty-eight matches of the knockout phase were evaluated post-event using a computerized notational analysis system. Multinomial logistic regression analysis was applied to identify the effects of the previously mentioned situational variables on ball recovery type and zone. Match status and quality of opposition main effects were observed for both dependent variables, while main effects of match location were only evident for ball recovery zone. Additionally, the interactions Match location (*) Quality of opposition and Match status (*) Quality of opposition were significant for both type and zone of ball recovery. Better teams employed more proactive defensive strategies, since, even when winning, they tried to sustain their defensive success on actions that aimed to gain the ball from the opponents. Results emphasized the tendency for home and losing teams to defend in more advanced pitch zones. Better-ranked teams were also more effective than worse-ranked teams in applying defensive pressure in more advanced pitch positions. The findings of the study suggest that the defensive strategies used by better teams imply more intense and organized collective processes in order to recover the ball directly from the opposing team. Furthermore, defending away from own goal and near the opponent's one seems to be associated with success in elite soccer. PMID- 25114748 TI - The examination of different tests for the evaluation of the efficiency of the eggbeater kicks. AB - The eggbeater kick presents an important basic technical skill in water polo. The aim of this study was to examine some different tests in order to recommend the best ones for the evaluation of the eggbeater kick. Twenty eight young male water polo players performed one test (squat jump) on land and ten tests in water: tethered swimming with legs only, using alternating and simultaneous eggbeater kicks, jumps out of water from basic and vertical (arms vertically above the head) position, water start and swimming two meters and swimming horizontally with legs only five meters with a flying start. The differences between tests were checked by executing dependent t-tests, while Pearson's correlation coefficients were calculated to evaluate the correlation between different parameters. Results showed that when performing alternate eggbeater kicks greater average forces were produced by the water polo players when compared to consecutive simultaneous eggbeater kicks. However, a short time maximal acceleration of the body in the vertical and horizontal plane was greater when the single simultaneous kick was performed. It was determined that horizontal swimming using legs only and a squat jump were less useful for the evaluation of the eggbeater kick. Therefore, the recommendation was to measure the average force of successive alternating eggbeater kicks, the height of the jump out of the water from the basic position and the water start and swim over a distance of 2 meters. PMID- 25114749 TI - Isokinetic leg strength and power in elite handball players. AB - Isokinetic strength evaluation of the knee flexion and extension in concentric mode of contraction is an important part of the comprehensive evaluation of athletes. The aims of this study were to evaluate the isokinetic knee peak torque in both the extension and flexion movement in the dominant and non-dominant leg, and the relationship with jumping performance. Twelve elite male handball players from the top Spanish handball division voluntary participated in the study (age 27.68 +/- 4.12 years; body mass 92.89 +/- 12.34 kg; body height 1.90 +/- 0.05 m). The knee extensor and flexor muscle peak torque of each leg were concentrically measured at 60o/s and 180o/s with an isokinetic dynamometer. The Squat Jump and Countermovement Jump were performed on a force platform to determine power and vertical jump height. Non-significant differences were observed between legs in the isokinetic knee extension (dominant= 2.91 +/- 0.53 Nm/kg vs non-dominant = 2.70 +/- 0.47 Nm/kg at 60o/s; dominant = 1.90 +/- 0.31 Nm/kg vs non-dominant = 1.83 +/- 0.29 Nm/kg at 180o/s) and flexion peak torques (dominant = 1.76 +/- 0.29 Nm/kg vs non-dominant = 1.72 +/- 0.39 Nm/kg at 60o/s; dominant = 1.30 +/- 0.23 Nm/kg vs non-dominant = 1.27 +/- 0.35 Nm/kg at 180o/s). Low and non-significant correlation coefficients were found between the isokinetic peak torques and vertical jumping performance (SJ = 31.21 +/- 4.32 cm; CMJ = 35.89 +/- 4.20 cm). Similar isokinetic strength was observed between the legs; therefore, no relationship was found between the isokinetic knee flexion and extension peak torques as well as vertical jumping performance in elite handball players. PMID- 25114750 TI - Fitness profiles of elite portuguese rugby union players. AB - The aim of this study was to describe the fitness profiles of senior elite Portuguese rugby players. Forty-six senior Portuguese rugby players, classified as backs (n=22; age 26.2+/-2.8) and forwards (n=24; age 26.7+/-2.9) were assessed during physical testing sessions carried out for the Portuguese National rugby team. The body composition, maximum strength and anaerobic capacity of players are hypothesized to be important physical characteristics as successful performance in rugby is predicated on the ability to undertake skilled behaviours both quickly and whilst withstanding large forces when in contact situations. No absolute differences were found between the backs and forwards for the speed performance variables although positional differences were found across all speeds when assessed relative to body mass since the forwards were significantly heavier. Coaches and the management team can use this information for monitoring progressive improvements in the physiological capacities of rugby players. These physical characteristics of elite rugby players provide normative profiles for specific positions and should form the basis of developmental programmes for adolescents. PMID- 25114751 TI - Physical Fitness Differences between Freestyle and Greco-Roman Junior Wrestlers. AB - The aim of the present study was to examine physical fitness differences between Freestyle and Greco-Roman junior wrestlers. One hundred twenty-six junior wrestlers, comprising 70 Freestyle and 56 Greco-Roman wrestlers, participated in this study. The somatic and physical fitness profile included body mass, body height, body mass index, body composition, flexibility, maximal anaerobic power of the legs and arms, aerobic endurance, hand grip strength, leg and back strength, and speed. No significant differences were found in the anthropometric and physical features between Freestyle and Greco-Roman wrestlers. The Greco Roman wrestlers had a significantly higher level of relative leg power, peak arm power, relative peak arm power, and relative average arm power than Freestyle wrestlers (p < 0.05). Greco-Roman wrestlers were significantly faster, had better agility, and had a greater level of leg strength than Freestyle wrestlers, but Freestyle wrestlers were more flexible than Greco-Roman wrestlers (p < 0.05). Discriminant function analysis indicated that peak arm power, agility, speed, and flexibility were selective factors for the differences between Freestyle and Greco-Roman wrestlers. In conclusion, the present study indicates that the differences between these wrestling styles promote physical fitness differences in elite wrestlers. The results reflect specific features of each wrestling style. PMID- 25114752 TI - Knowledge of errors in the teaching-learning process of judo-techniques: osoto guruma as a case study. AB - The aim of this article was to suggest some changes in the teaching-learning process methodology of the judo osoto-guruma technique, establishing the action sequences and the most frequent technical errors committed when performing them. The study was carried out with the participation of 45 students with no experience regarding the fundamentals of judo (21 men and 24 women; age=24.02+/ 3.98 years old) from the Bachelor of Science of Physical Activity and Sport Science at the University of Vigo. The proceeding consisted of a systematic observation of a video recording registered during the technique execution. Data obtained were analyzed by means of descriptive statistics and sequential analysis of T-Patterns (obtained with THEME v.5. Software), identifying: a) the presence of typical inaccuracies during the technique performance; b) a number of chained errors affecting body balance, the position of the supporting foot, the blocking action and the final action of the arms. Findings allowed to suggest some motor tasks to correct the identified inaccuracies, the proper sequential actions to make the execution more effective and some recommendations for the use of feedback. Moreover, these findings could be useful for other professionals in order to correct the key technical errors and prevent diverse injuries. PMID- 25114753 TI - Transference of traditional versus complex strength and power training to sprint performance. AB - The purpose of this study was to determine the effects of two different strength power training models on sprint performance. Forty-eight soldiers of the Brazilian brigade of special operations with at least one year of army training experience were divided into a control group (CG: n = 15, age: 20.2 +/- 0.7 years, body height: 1.74 +/- 0.06 m, and body mass: 66.7 +/- 9.8 kg), a traditional training group (TT: n = 18, age: 20.1 +/- 0.7 years, body height: 1.71 +/- 0.05 m, and body mass: 64.2 +/- 4.7 kg), and a complex training group (CT: n = 15, age: 20.3 +/- 0.8 years, body height: 1.71 +/- 0.07 m; and body mass: 64.0 +/- 8.8 kg). Maximum strength (25% and 26%), CMJ height (36% and 39%), mean power (30% and 35%) and mean propulsive power (22% and 28%) in the loaded jump squat exercise, and 20-m sprint speed (16% and 14%) increased significantly (p<=0.05) following the TT and CT, respectively. However, the transfer effect coefficients (TEC) of strength and power performances to 20-m sprint performance following the TT were greater than the CT throughout the 9-week training period. Our data suggest that TT is more effective than CT to improve sprint performance in moderately trained subjects. PMID- 25114755 TI - Contemporary transcatheter interventions in adult congenital heart disease. PMID- 25114756 TI - Developing tools to measure quality in congenital catheterization and interventions: the congenital cardiac catheterization project on outcomes (C3PO). AB - The broad range of relatively rare procedures performed in pediatric cardiac catheterization laboratories has made the standardization of care and risk assessment in the field statistically quite problematic. However, with the growing number of patients who undergo cardiac catheterization, it has become imperative that the cardiology community overcomes these challenges to study patient outcomes. The Congenital Cardiac Catheterization Project on Outcomes was able to develop benchmarks, tools for measurement, and risk adjustment methods while exploring procedural efficacy. Based on the success of these efforts, the collaborative is pursuing a follow-up project, the Congenital Cardiac Catheterization Project on Outcomes-Quality Improvement, aimed at improving the outcomes for all patients undergoing catheterization for congenital heart disease by reducing radiation exposure. PMID- 25114758 TI - Stem cell therapies in patients with single ventricle physiology. AB - Single ventricle physiology, especially hypoplastic left heart syndrome, is one of the most high-risk lesions in children with congenital heart disease, and the ensuing heart failure remains as a major problem related to adverse outcomes in these patients. The field of stem cell therapy for heart failure has shown striking advances during the past 10 years, and many clinical trials using stem cell technologies have been conducted in adults, which suggest that stem cell therapy is associated with long-term improvement in cardiac function. Cardiac progenitor cells have recently been discovered, and their strong regenerative ability has been demonstrated in several studies. Although no large clinical trials have been performed in the field of congenital heart disease, recent investigations indicate that stem cell therapy may hold great potential to treat children with cardiac defects. PMID- 25114759 TI - Intravascular stent therapy for coarctation of the aorta. AB - Intravascular stent therapy is considered a primary therapeutic option for most adults and adolescents with coarctation of the aorta. This review highlights the indications, technical considerations, procedural aspects, and limited long-term outcome data when using this intervention. Stent technology has continued to evolve with potential for further modifications since its inception in the early 1990s. The best therapeutic approach, e.g., stenting versus surgery, in the treatment of native coarctation continues to be debated due to the paucity of long-term clinical and imaging data in both groups. PMID- 25114757 TI - Multimodality 3-dimensional image integration for congenital cardiac catheterization. AB - Cardiac catheterization procedures for patients with congenital and structural heart disease are becoming more complex. New imaging strategies involving integration of 3-dimensional images from rotational angiography, magnetic resonance imaging (MRI), computerized tomography (CT), and transesophageal echocardiography (TEE) are employed to facilitate these procedures. We discuss the current use of these new 3D imaging technologies and their advantages and challenges when used to guide complex diagnostic and interventional catheterization procedures in patients with congenital heart disease. PMID- 25114760 TI - Hybrid interventional procedures in congenital heart disease. AB - The evolution of congenital cardiac surgery has seen significant innovative advances in collaborative efforts between congenital cardiac surgeons and interventionalists to provide the least invasive intervention with the greatest hemodynamic benefit for patients with congenital heart disease. This review looks at how this collaborative approach has evolved and is being applied to treat a number of congenital conditions across the age ranges. PMID- 25114761 TI - Modern medical management of acute ischemic stroke. AB - The modern management of patients with ischemic stroke begins by having a system in place that organizes the provision of preventive, acute treatment, and rehabilitative services. In the acute setting, initial evaluation is aimed at rapidly establishing a diagnosis by excluding stroke mimics, distinguishing between ischemic and hemorrhagic strokes, and determining if the patient is a candidate for treatment with intravenous tissue plasminogen activator (IV-tPA, alteplase). In some centers, select patients who do not qualify for administration of IV-tPA may be considered for endovascular intervention. General measures include the use of platelet antiaggregants, treatment of fever, blood pressure management, and continuation of statins if the patient has already been taking them. Post-acute evaluation and management is aimed at secondary prevention and optimizing recovery, including recognition and treatment of post stroke depression. PMID- 25114762 TI - Modern interventional management of stroke. AB - Acute ischemic stroke continues to be one of the leading causes of disability and death and is a financial burden to an already taxed health care system. Much research and investigation has been carried out over the past decade on various recanalization devices aimed at restoring cerebral blood flow. Despite the rapidly improving technical abilities of these devices, it has been difficult to demonstrate corresponding improved clinical outcomes. This article will describe the application of the most recent generation of these devices and briefly discuss the ongoing discrepancy between these technical achievements and stroke outcomes. PMID- 25114764 TI - Case report: incidental finding of a giant cardiac mass. AB - Coronary artery fistula (CAF) is a rare anomalous connection between a coronary artery and another coronary artery, major vessel, or cardiac chamber. Prevalence of CAF is reportedly 1% to 2% in patients who undergo coronary angiography.1 One of the most common complications of CAF is formation of a coronary artery aneurysm (CAA). A study conducted by Said and colleagues in 1995 found that CAA formation was present in 26% of patients who had proven CAF by way of angiography.2 Although a precise definition of the term "giant" CAA is still lacking, it generally refers to a dilatation that exceeds the reference vessel diameter by four times.3 We report an interesting case of a 38-year-old patient who was incidentally found to have a presumed large right ventricular aneurysm, which after an open-heart surgery was identified as a CAF with formation of an unruptured giant CAA. PMID- 25114763 TI - Comparison of dexmedetomidine versus propofol for sedation in mechanically ventilated patients after cardiovascular surgery. AB - Many cardiovascular surgeries are fast-tracked to extubation and require short term sedation. Dexmedetomidine and propofol have very different mechanisms of action and pharmacokinetic profiles that make them attractive sedative agents in this patient population. Recently, there has been increased use of dexmedetomidine in the intensive care unit (ICU), but few studies exist or have been published directly comparing both agents in this setting. We conducted a retrospective cohort study with patients admitted to the ICU after cardiovascular surgery from January through June 2011. Adult patients who underwent coronary artery bypass and/or cardiac valve surgery received either dexmedetomidine or propofol continuous infusion for short-term sedation after cardiovascular surgery. The primary end point was time (hours) on mechanical ventilation after surgery. Secondary end points included ICU length of stay (LOS), hospital LOS, incidence of delirium, and requirement of a second sedative agent. A total of 352 patients met study inclusion criteria, with 33 enrolled in the dexmedetomidine group and 319 in the propofol group. Time on mechanical ventilation was shorter in the dexmedetomidine group (7.4 hours vs. 12.9 hours, P = .042). No difference was seen in ICU or hospital LOS. The need for a second sedative agent to achieve optimal sedation (24% vs. 27%, P = .737) and incidence of delirium (9% vs. 7.5%, P = .747) were similar between both groups. Sedation with dexmedetomidine resulted in a significant reduction in time on mechanical ventilation. However, no difference was seen in ICU or hospital LOS, incidence of delirium, or mortality. PMID- 25114765 TI - Case report: single coronary artery with ischemia and sudden cardiac arrest. AB - Single coronary artery (SCA) is a very rare finding. Although most cases of SCA are found incidentally on coronary angiography, it can potentially lead to different clinical repercussions.1, 2 Herein we describe a patient with SCA who had unstable angina with subsequent sudden cardiac arrest, and we provide a brief review of the recent literature. PMID- 25114767 TI - Museum of TMH multimodality imaging center: ruptured sinus of valsalva aneurysm with an odd presentation. PMID- 25114766 TI - Case report: cardiac tamponade resembling an acute myocardial infarction as the initial manifestation of metastatic pericardial adenocarcinoma. AB - Pericardial malignancies are uncommon, usually metastatic, linked to terminal oncology patients, and rarely diagnosed premortem. A very small number of patients will develop signs and symptoms of malignant pericardial effusion as initial clinical manifestation of neoplastic disease. Among these patients, a minority will progress to a life-threatening cardiac tamponade. It is exceedingly rare for a cardiac tamponade to be the unveiling clinical manifestation of an unknown malignancy, either primary or metastatic to pericardium. We present the case of a 50-year-old male who was admitted to the emergency department with an acute myocardial infarction diagnosis that turned out to be a cardiac tamponade of unknown etiology. Further studies revealed a metastatic pericardial adenocarcinoma with secondary cardiac tamponade. We encourage considering malignancies metastatic to pericardium as probable etiology for large pericardial effusions and cardiac tamponade of unknown etiology. PMID- 25114768 TI - Museum of TMH multimodality imaging center: cardiac amyloidosis. PMID- 25114769 TI - Points to remember: frequently encountered urologic problems after cardiovascular surgery. PMID- 25114774 TI - On being a doctor: ask, why? PMID- 25114776 TI - 5-(Methylthio)tetrazoles as Versatile Synthons in the Stereoselective Synthesis of Polycyclic Pyrazolines via Photoinduced Intramolecular Nitrile Imine-Alkene 1,3-Dipolar Cycloaddition. AB - A key thioether substituent in readily accessible 2-alkyl-5 (methylthio)tetrazoles enables facile photoinduced denitrogenation and intramolecular nitrile imine 1,3-dipolar cycloaddition to afford a wide range of polycyclic pyrazoline products with excellent diastereoselectivity. The methylthio group red-shifts the UV absorbance of the tetrazole, obviating the requirement in all previous substrate systems for at least one aryl substituent, and can subsequently be converted into a variety of other functionalities. This synthetic platform has been applied to the concise total syntheses of the alkaloid natural products (+/-)-newbouldine and withasomnine. PMID- 25114777 TI - A study on drug-drug interactions through prescription analysis in a South Indian teaching hospital. AB - OBJECTIVE: The objective of this study was to assess the drug-drug interactions (DDIs) through prescription analysis among the inpatients of a South Indian teaching hospital. METHODS: The study was a prospective observational prescription analysis conducted for a period of 6 months, from October 2010 to March 2011. The prescriptions having two or more drugs and where a DDI was suspected were selected by the physician in charge of the ward. The drugs in the prescription were then entered into the drug interaction checker software. The DDIs were classified based on the mechanism of interactions, severity of interactions, relation to the number of drugs prescribed, and disease conditions were also determined. RESULTS: A total of 204 prescriptions were analyzed, of which 186 prescriptions had 856 DDIs. Most of the DDIs were pharmacokinetic drug interactions (42%) followed by unknown mechanisms (34%) and pharmacodynamic mechanisms (24%). The study findings showed that the prescriptions for cardiovascular with respiratory disease conditions had the greatest number of drug interactions on average. A severity assessment showed that majority of the DDIs were moderate (70%) followed by minor (28%). The study results showed that as the number of drugs increases in a prescription, the number of DDIs also increases. The interventions determined showed that dosage adjustment (12%) was to be followed in most of the DDIs. CONCLUSION: This study assists in understanding the factors associated with DDIs that can help in safe and effective use of drugs in the future. PMID- 25114775 TI - SOX2 and cancer: current research and its implications in the clinic. AB - SOX2 is a gene that encodes for a transcription factor belonging to the SOX gene family and contains a high-mobility group (HMG) domain, which permits highly specific DNA binding. Consequently, SOX2 functions as an activator or suppressor of gene transcription. SOX2 has been described as an essential embryonic stem cell gene and moreover, a necessary factor for induced cellular reprogramming. SOX2 research has only recently switched focus from embryogenesis and development to SOX2's function in disease. Particularly, the role of SOX2 in cancer pathogenesis has become of interest in the field. To date, studies have shown SOX2 to be amplified in various cancer types and affect cancer cell physiology via involvement in complicated cell signaling and protein-protein interactions. Recent reviews in this field have highlighted SOX2 in mammalian physiology, development and pathology. In this review, we comprehensively compile what is known to date about SOX2's involvement in cancer biology, focusing on the most recent findings in the fields of cellular signaling and cancer stem cells. Lastly, we underscore the role of SOX2 in the clinic and highlight new findings, which may provide novel clinical applications for SOX2 as a prognostic marker, indicator of metastasis, biomarker or potential therapeutic target in some cancer types. PMID- 25114778 TI - Drug-related falls in older patients: implicated drugs, consequences, and possible prevention strategies. AB - Falls are the leading cause of injuries among older adults, aged 65 years and older. Furthermore, falls are an increasing public health problem because of ageing populations worldwide due to an increase in the number of older adults, and an increase in life expectancy. Numerous studies have identified risk factors and investigated possible strategies to prevent (recurrent) falls in community dwelling older people and those living in long-term care facilities. Several types of drugs have been associated with an increased fall risk. Since drugs are a modifiable risk factor, periodic drug review among older adults should be incorporated in a fall prevention programme. PMID- 25114779 TI - Safety of antiobesity drugs. AB - Obesity is a major health problem worldwide. Although diet and physical activity are crucial in the management of obesity, the long-term success rate is low. Therefore antiobesity drugs are of great interest, especially when lifestyle modification has failed. As obesity is not an immediate life-threatening disease, these drugs are required to be safe. Antiobesity drugs that have been developed so far have limited efficacies and considerable adverse effects affecting tolerability and safety. Therefore, most antiobesity drugs have been withdrawn. Fenfluramine and dexfenfluramine were withdrawn because of the potential damage to heart valves. Sibutramine was associated with an increase in major adverse cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial and it was withdrawn from the market in 2010. Rimonabant was withdrawn because of significant psychiatric adverse effects. Orlistat was approved in Europe and the United States for long-term treatment of obesity, but many patients cannot tolerate its gastrointestinal side effects. Phentermine and diethylpropion can only be used for less than 12 weeks because the long-term safety of these drugs is unknown. Ephedrine and caffeine are natural substances but the effects on weight reduction are modest. As a result there is a huge unmet need for effective and safe antiobesity drugs. Recently lorcaserin and topiramate plus phentermine have been approved for the treatment of obesity but long-term safety data are lacking. PMID- 25114782 TI - Monitoring product safety in the postmarketing environment. AB - The safety profile of a medicinal product may change in the postmarketing environment. Safety issues not identified in clinical development may be seen and need to be evaluated. Methods of evaluating spontaneous adverse experience reports and identifying new safety risks include a review of individual reports, a review of a frequency distribution of a list of the adverse experiences, the development and analysis of a case series, and various ways of examining the database for signals of disproportionality, which may suggest a possible association. Regulatory agencies monitor product safety through a variety of mechanisms including signal detection of the adverse experience safety reports in databases and by requiring and monitoring risk management plans, periodic safety update reports and postauthorization safety studies. The United States Food and Drug Administration is working with public, academic and private entities to develop methods for using large electronic databases to actively monitor product safety. Important identified risks will have to be evaluated through observational studies and registries. PMID- 25114780 TI - Selective serotonin reuptake inhibitors and torsade de pointes: new concepts and new directions derived from a systematic review of case reports. AB - OBJECTIVE: In the light of the recent United States Food and Drug Administration (FDA) warning to clinicians on using previously approved doses of citalopram because of the purported higher risk of torsade de pointes (TdP), we pursued the broader question: are selective serotonin reuptake inhibitor (SSRI) antidepressant agents as a group unsafe because they might induce QTc interval prolongation and TdP? METHOD: We reviewed the literature and found only 15 case reports (6 of fluoxetine, 1 of sertraline and 8 of citalopram) of SSRI-associated QTc interval prolongation linking to TdP. RESULTS: A total of 13 cases contained sufficient information for analysis. In the setting of TdP, QTc interval prolongation does not clearly relate to SSRI dose. CONCLUSION: Applying conventional statistics as the FDA does may not be the best tool to study this phenomenon because SSRI-associated TdP is a very rare event and hence best understood as an 'extreme outlier'. Despite the limitations inherent in case report material, case reports on drug-associated QTc interval prolongation and TdP provide valuable information that should be considered along with other sources of information for clinical guidance. PMID- 25114783 TI - Preparing for safety issues following drug approval: pre-approval risk management considerations. AB - Risk management plans and risk minimization plans as well as postapproval commitment studies are based on risks identified pre-approval that need to be further characterized or minimized in the postmarketing environment. Although the implementation of these activities are conducted in the postapproval arena, the design of the plans and studies as well as the development of effective postapproval tools and mitigation strategies should be carried out pre-approval. The pre-approval period also provides the opportunity to fully understand the treatment population that is included in the clinical trial program and to determine how the target population for the drug after approval may differ from the clinical trial patient population. When regulators or sponsors have expressed concerns about safety issues identified during clinical development, the result may be a postapproval commitment in the form of a registry or an observational safety study or, in the US, a Risk Evaluation and Mitigation Strategy (REMS) as a condition of approval. Specific examples are given for risk mitigation activities that can be conducted pre-approval. PMID- 25114781 TI - Calcium supplements and cardiovascular risk: 5 years on. AB - Calcium supplements have been widely used by older men and women. However, in little more than a decade, authoritative recommendations have changed from encouraging the widespread use of calcium supplements to stating that they should not be used for primary prevention of fractures. This substantial shift in recommendations has occurred as a result of accumulated evidence of marginal antifracture efficacy, and important adverse effects from large randomized controlled trials of calcium or coadministered calcium and vitamin D supplements. In this review, we discuss this evidence, with a particular focus on increased cardiovascular risk with calcium supplements, which we first described 5 years ago. Calcium supplements with or without vitamin D marginally reduce total fractures but do not prevent hip fractures in community-dwelling individuals. They also cause kidney stones, acute gastrointestinal events, and increase the risk of myocardial infarction and stroke. Any benefit of calcium supplements on preventing fracture is outweighed by increased cardiovascular events. While there is little evidence to suggest that dietary calcium intake is associated with cardiovascular risk, there is also little evidence that it is associated with fracture risk. Therefore, for the majority of people, dietary calcium intake does not require close scrutiny. Because of the unfavorable risk/benefit profile, widespread prescribing of calcium supplements to prevent fractures should be abandoned. Patients at high risk of fracture should be encouraged to take agents with proven efficacy in preventing vertebral and nonvertebral fractures. PMID- 25114784 TI - Associations between different measures of anticholinergic drug exposure and Barthel Index in older hospitalized patients. AB - OBJECTIVE: To compare associations between four measures of anticholinergic exposure (anticholinergic risk scale, ARS; anticholinergic drug burden, DBAC; number and use versus no use of anticholinergic drugs), Barthel Index (BI, physical function) and Abbreviated Mental Test (AMT, cognitive function) on admission in older hospitalized patients. METHODS: Prospective observational study of a consecutive series of 271 older patients (age 83 +/- 7 years) from community-dwelling and institutionalized settings, admitted to an acute geriatric admission unit between 28 September 2011 and 18 December 2011. The main outcome measures were BI quartiles (primary outcome) and AMT (secondary outcome) on admission. RESULTS: Anticholinergic prevalence was 47%. Multinomial logistic regression showed higher DBAC was associated with a greater risk of being in the lower BI quartiles versus highest BI quartile (Q4). This risk was significant for Q3 (p = 0.04) and Q2 (p = 0.02) but not for Q1 (p = 0.06). A greater number of anticholinergic drugs was associated with a higher risk of being in Q2 (p = 0.02). This risk was not significant for either Q3 (p = 0.10) or Q1 (p = 0.06). No significant associations were observed either with use of anticholinergic medication or with ARS and BI quartiles. AMT did not show independent associations with any of the four measures of anticholinergic exposure. CONCLUSION: In older hospitalized patients, DBAC and some crude measures of anticholinergic exposure, but not ARS, showed independent associations with lower BI, but not AMT. These results highlight differences between various measures of anticholinergic drug exposure when studying their associations with functional status. PMID- 25114785 TI - The risk of cutaneous adverse reactions among patients with the HLA-A* 31:01 allele who are given carbamazepine, oxcarbazepine or eslicarbazepine: a perspective review. AB - Carbamazepine is a drug that is widely used for the treatment of epilepsy, trigeminal neuralgia and bipolar disorder. This drug is also known to cause cutaneous adverse drug reactions (cADRs) in up to 10% of patients. The recent progress in pharmacogenetics has revealed that human leukocyte antigen (HLA) genotypes are associated with a susceptibility to the cADRs caused by particular drugs. For carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis, very strong associations with HLA-B*15:02 have been found mainly in patients of Southeastern Asian origin. In some countries, prescreening HLA B*15:02 allele has already been put to practical use as a biomarker to avoid the life-threatening adverse drug reactions. In this review, another risk factor for carbamazepine-induced cADRs is discussed, namely HLA-A*31:01. We compare the strength of the association between HLA-A*31:01 and carbamazepine-induced cADRs based on reports for various ethnic populations; discuss the difference between the HLA-A*31:01 and HLA-B*15:02 biomarkers and the usefulness of prescreening HLA A*31:01 to detect patients at high risk for carbamazepine-induced cADRs; and refer to points that remain to be resolved. PMID- 25114786 TI - Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma. AB - The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration. PMID- 25114787 TI - Evaluation of side effects of radiofrequency capacitive hyperthermia with magnetite on the blood vessel walls of tumor metastatic lesion surrounding the abdominal large vessels: an agar phantom study. AB - BACKGROUND: Magnetite used in an 8-MHz radiofrequency (RF) capacitive heating device can increase the temperature of a specific site up to 45 degrees C. When treating a metastatic lesion around large abdominal vessels via hyperthermia with magnetite, heating-induced adverse effects on these vessels need to be considered. Therefore, this study examined hyperthermia-induced damage to blood vessel walls in vitro. METHODS: A large agar phantom with a circulatory system consisting of a swine artery and vein connected to a peristaltic pump was prepared. The blood vessels were placed on the magnetite-containing agar piece. Heating was continued for 30 min at 45 degrees C. After heating, a histological study for injury to the blood vessels was performed. RESULTS: The inner membrane temperature did not reach 45 degrees C due to the cooling effect of the blood flow. In the heated vessels, vascular wall collagen degenerated and smooth muscle cells were narrowed; however, no serious changes were noted in the vascular endothelial cells or vascular wall elastic fibers. The heated vessel wall was not severely damaged; this was attributed to cooling by the blood flow. CONCLUSIONS: Our findings indicate that RF capacitive heating therapy with magnetite may be used for metastatic lesions without injuring the surrounding large abdominal vessels. PMID- 25114788 TI - Active video gaming in patients with renal transplant: a pilot study. AB - BACKGROUND: Patients with renal transplant are at higher risk of mortality from cardiovascular disease (CVD) compared with the general population. Physical activity has been shown to reduce the risk of CVD mortality in these patients. Unfortunately, barriers such as the harsh Canadian climate prevent patients from engaging in and harvesting the health benefits of physical activity. This pilot study explored active video gaming (AVG) as a way for patients with renal transplant to obtain physical activity and examined its effect on their functional status and quality of life (QOL). MAIN TEXT: We recruited nine patients for an 8-week prospective pilot study. All patients received a Microsoft Xbox 360TM video gaming console, a Microsoft KinectTM sensor, and the video game Your Shape Fitness Evolved 2012. Assessment of each participant before and after the intervention included blood pressure measures, a 6-minute walk test, and the Godin Leisure Time Questionnaire (GLTQ). We analyzed all nine patients at the end of the 8-week study period, and found no changes in blood pressure or GLTQ scores. However, there was a significant increase in the 6-minute walk distance (P = 0.022), which represented a consistent increase for most patients (correlation = 0.977). In addition, participants over the age of 45 years (n = 4) were more likely to use the AVG system (P = 0.042). CONCLUSION: AVG has the potential to improve the functional status in patients with renal transplant. Further research is required to corroborate the full health benefits of AVG in this patient population. PMID- 25114789 TI - The efficacy and safety of pramipexole ER versus IR in Chinese patients with Parkinson's disease: a randomized, double-blind, double-dummy, parallel-group study. AB - OBJECTIVE: To evaluate the non-inferiority of pramipexole extended-release (ER) versus immediate-release (IR) in Chinese patients with Parkinson's disease (PD) in a double-blind, randomized, parallel-group study. METHODS: Subjects were Chinese patients with idiopathic PD with diagnosis >= 2 years prior to trial, age >= 30 years old at diagnosis, and Modified Hoehn and Yahr score 2-4 during 'on' time. Subjects received treatment with pramipexole ER (n=234) or IR (n=239). Non inferiority was based on the primary endpoint, the change from baseline to end of maintenance (week 18) in the UPDRS (Parts II + III) total score. RESULTS: For the primary endpoint, the adjusted mean changes (standard error) of UPDRS Parts II + III at week 18 were -13.81 (0.655) and -13.05 (0.643) for ER and IR formulations, respectively, using ANCOVA adjusted for treatment and centre (fixed effect) and baseline (covariate). The adjusted mean between group difference was 0.8 for the 2-sided 95% CI (-1.047, 2.566). Since the lower limit of the 2-sided 95% CI ( 1.047) for treatment difference was higher than the non-inferiority margin of -4, non-inferiority between pramipexole ER and IR was demonstrated. The incidence of adverse events (AEs) was 68.8% in the ER arm and 73.6% in the IR arm with few severe AEs (ER: 2.1%; IR: 3.8%). CONCLUSION: Based on the UPDRS II + III score, pramipexole ER was non-inferior to pramipexole IR. The safety profiles of pramipexole ER and IR were similar. These results were based on comparable mean daily doses and durations of treatment for both formulations. PMID- 25114790 TI - Measles-mumps-rubella vaccination timing and autism among young African American boys: a reanalysis of CDC data. AB - BACKGROUND: A significant number of children diagnosed with autism spectrum disorder suffer a loss of previously-acquired skills, suggesting neurodegeneration or a type of progressive encephalopathy with an etiological basis occurring after birth. The purpose of this study is to investigate the effectof the age at which children got their first Measles-Mumps-Rubella (MMR) vaccine on autism incidence. This is a reanalysis of the data set, obtained from the U.S. Centers for Disease Control and Protection (CDC), used for the Destefano et al. 2004 publication on the timing of the first MMR vaccine and autism diagnoses. METHODS: The author embarked on the present study to evaluate whether a relationship exists between child age when the first MMR vaccine was administered among cases diagnosed with autism and controls born between 1986 through 1993 among school children in metropolitan Atlanta. The Pearson's chi squared method was used to assess relative risks of receiving an autism diagnosis within the total cohort as well as among different race and gender categories. RESULTS: When comparing cases and controls receiving their first MMR vaccine before and after 36 months of age, there was a statistically significant increase in autism cases specifically among African American males who received the first MMR prior to 36 months of age. Relative risks for males in general and African American males were 1.69 (p=0.0138) and 3.36 (p=0.0019), respectively. Additionally, African American males showed an odds ratio of 1.73 (p=0.0200) for autism cases in children receiving their first MMR vaccine prior to 24 months of age versus 24 months of age and thereafter. CONCLUSIONS: The present study provides new epidemiologic evidence showing that African American males receiving the MMR vaccine prior to 24 months of age or 36 months of age are more likely to receive an autism diagnosis. PMID- 25114791 TI - A review of the use of health examination data from the Health Survey for England in government policy development and implementation. AB - BACKGROUND: Information is needed at all stages of the policy making process. The Health Survey for England (HSE) is an annual cross-sectional health examination survey of the non-institutionalised general population in England. It was originally set up to inform national policy making and monitoring by the Department of Health. This paper examines how the nurse collected physical and biological measurement data from the HSE have been essential or useful for identification of a health issue amenable to policy intervention; initiation, development or implementation of a strategy; choice and monitoring of targets; or assessment and evaluation of policies. METHODS: Specific examples of use of HSE data were identified through interviews with senior members of staff at the Department of Health and the Health and Social Care Information Centre. Policy documents mentioned by interviewees were retrieved for review, and reference lists of associated policy documents checked. Systematic searches of Chief Medical Officer Reports, Government 'Command Papers', and clinical guidance documents were also undertaken. RESULTS: HSE examination data have been used at all stages of the policy making process. Data have been used to identify an issue amenable to policy-intervention (e.g. quantifying prevalence of undiagnosed chronic kidney disease), in strategy development (in models to inform chronic respiratory disease policy), for target setting and monitoring (the 1992 blood pressure target) and in evaluation of health policy (the effect of the smoking ban on second hand smoke exposure). CONCLUSIONS: A health examination survey is a useful part of a national health information system. PMID- 25114792 TI - Factors associated with data quality in the routine health information system of Benin. AB - BACKGROUND: Routine health information systems (RHIS) are crucial to the acquisition of data for health sector planning. In developing countries, the insufficient quality of the data produced by these systems limits their usefulness in regards to decision-making. The aim of this study was to identify the factors associated with poor data quality in the RHIS in Benin. METHODS: This cross-sectional descriptive and analytical study included health workers who were responsible for data collection in public and private health centers. The technique and tools used were an interview with a self-administered questionnaire. The dependent variable was the quality of the data. The independent variables were socio-demographic and work-related characteristics, personal and work-related resources, and the perception of the technical factors. The quality of the data was assessed using the Lot Quality Assurance Sampling method. We used survival analysis with univariate proportional hazards (PH) Cox models to derive hazards ratios (HR) and their 95% confidence intervals (95% CI). Focus group data were evaluated with a content analysis. RESULTS: A significant link was found between data quality and level of responsibility (p = 0.011), sector of employment (p = 0.007), RHIS training (p = 0.026), level of work engagement (p < 0.001), and the level of perceived self-efficacy (p = 0.03). The focus groups confirmed a positive relationship with organizational factors such as the availability of resources, supervision, and the perceived complexity of the technical factors. CONCLUSION: This exploratory study identified several factors associated with the quality of the data in the RHIS in Benin. The results could provide strategic decision support in improving the system's performance. PMID- 25114794 TI - Community based interventions for the prevention and control of Non-Helmintic NTD. AB - In this paper, we aim to systematically analyze the effectiveness of community based interventions (CBI) for the prevention and control of non-helminthic diseases including dengue, trypanosomiasis, chagas, leishmaniasis, buruli ulcer, leprosy and trachoma. We systematically reviewed literature published up to May 2013 and included 62 studies in this review. Findings from our review suggest that CBI including insecticide spraying; insecticide treated bednets and curtains; community education and cleanliness campaigns; chemoprophylaxis through mass drug administration; and treatment have the potential to reduce the incidence and burden of non-helminthic diseases. Lack of data limited the subgroup analysis for integrated and non-integrated delivery strategies however, qualitative synthesis suggest that integrated delivery is more effective when compared to vertical interventions; however, such integration was possible only because of the existing vertical vector control programs. Community delivered interventions have the potential to achieve wider coverage and sustained community acceptance. Eradicating these diseases will require a multipronged approach including drug administration, health education, vector control and clean water and sanitation facilities. This would require high level governmental commitment along with strong partnerships among major stakeholders. PMID- 25114793 TI - Community-based interventions for the prevention and control of helmintic neglected tropical diseases. AB - In this paper, we aim to systematically analyze the effectiveness of community based interventions (CBIs) for the prevention and control of helminthiasis including soil-transmitted helminthiasis (STH) (ascariasis, hookworms, and trichuriasis), lymphatic filariasis, onchocerciasis, dracunculiasis, and schistosomiasis. We systematically reviewed literature published before May 2013 and included 32 studies in this review. Findings from the meta-analysis suggest that CBIs are effective in reducing the prevalence of STH (RR: 0.45, 95% CI: 0.38, 0.54), schistosomiasis (RR: 0.40, 95% CI: 0.33, 0.50), and STH intensity (SMD: -3.16, 95 CI: -4.28, -2.04). They are also effective in improving mean hemoglobin (SMD: 0.34, 95% CI: 0.20, 0.47) and reducing anemia prevalence (RR: 0.90, 95% CI: 0.85, 0.96). However, it did not have any impact on ferritin, height, weight, low birth weight (LBW), or stillbirths. School-based delivery significantly reduced STH (RR: 0.49, 95% CI: 0.39, 0.63) and schistosomiasis prevalence (RR: 0.50, 95% CI: 0.33, 0.75), STH intensity (SMD: -0.22, 95% CI: 0.26, -0.17), and anemia prevalence (RR: 0.87, 95% CI: 0.81, 0.94). It also improved mean hemoglobin (SMD: 0.24, 95% CI: 0.16, 0.32). We did not find any conclusive evidence from the quantitative synthesis on the relative effectiveness of integrated and non-integrated delivery strategies due to the limited data available for each subgroup. However, the qualitative synthesis from the included studies supports community-based delivery strategies and suggests that integrated prevention and control measures are more effective in achieving greater coverage compared to the routine vertical delivery, albeit it requires an existing strong healthcare infrastructure. Current evidence suggests that effective community based strategies exist and deliver a range of preventive, promotive, and therapeutic interventions to combat helminthic neglected tropical diseases (NTDs). However, there is a need to implement and evaluate efficient integrated programs with the existing disease control programs on a larger scale throughout resource-limited regions especially to reach the unreachable. PMID- 25114796 TI - Biomineralized matrix-assisted osteogenic differentiation of human embryonic stem cells. AB - The physical and chemical properties of a matrix play an important role in determining various cellular behaviors, including lineage specificity. We demonstrate that the differentiation commitment of human embryonic stem cells (hESCs), both in vitro and in vivo, can be solely achieved through synthetic biomaterials. hESCs were cultured using mineralized synthetic matrices mimicking a calcium phosphate (CaP)-rich bone environment differentiated into osteoblasts in the absence of any osteogenic inducing supplements. When implanted in vivo, these hESC-laden mineralized matrices contributed to ectopic bone tissue formation. In contrast, cells within the corresponding non-mineralized matrices underwent either osteogenic or adipogenic fate depending upon the local cues present in the microenvironment. To our knowledge, this is the first demonstration where synthetic matrices are shown to induce terminal cell fate specification of hESCs exclusively by biomaterial-based cues both in vitro and in vivo. Technologies that utilize tissue specific cell-matrix interactions to control stem cell fate could be a powerful tool in regenerative medicine. Such approaches can be used as a tool to advance our basic understanding and assess the translational potential of stem cells. PMID- 25114795 TI - Impact of community-based interventions for the prevention and control of malaria on intervention coverage and health outcomes for the prevention and control of malaria. AB - In this paper, we aim to evaluate the effectiveness of community-based interventions (CBIs) for the prevention and management of malaria. We conducted a systematic review and identified 42 studies for inclusion. Twenty-five of the included studies evaluated the impact of the community-based distribution of insecticide-treated nets (ITNs), indoor residual spraying (IRS), or impregnated bed sheets; 14 studies evaluated intermittent preventive therapy (IPT) delivered in community settings; two studies focused on community-based education for malaria prevention; and one study evaluated environmental management through drain cleaning. Our analysis suggests that, overall, the community-based delivery of interventions to prevent and control malaria resulted in a significant increase in ITNs ownership (RR: 2.16, 95% CI: 1.86, 2.52) and usage (RR: 1.77, 95% CI: 1.48, 2.11). However, usage of ITNs was limited to two-thirds of the population who owned them. Community-based strategies also led to a significant decrease in parasitemia (RR: 0.56, 95% CI: 0.42, 0.74), malaria prevalence (RR: 0.46, 95% CI: 0.29, 0.73), malaria incidence (RR: 0.70, 95% CI: 0.54, 0.90), and anemia prevalence (RR: 0.79, 95% CI: 0.64, 0.97). We found a non-significant impact on splenomegaly, birth outcomes (low birth weight, prematurity, stillbirth/miscarriage), anthropometric measures (stunting, wasting, and underweight), and mortality (all-cause and malaria-specific). The subgroup analysis suggested that community-based distribution of ITNs, impregnated bed sheets and IRS, and IPT are effective strategies. Qualitative synthesis suggests that high coverage could be achieved at a lower cost with the integration of CBIs with existing antenatal care and immunization campaigns. Community-based delivery of interventions to prevent and control malaria are effective strategies to improve coverage and access and reduce malaria burden, however, efforts should also be concerted to prevent over diagnosis and drug resistance. PMID- 25114797 TI - Rapid clearance of epigenetic protein reporters from wound edge cells in Drosophila larvae does not depend on the JNK or PDGFR/VEGFR signaling pathways. AB - The drastic cellular changes required for epidermal cells to dedifferentiate and become motile during wound closure are accompanied by changes in gene transcription, suggesting corresponding alterations in chromatin. However, the epigenetic changes that underlie wound-induced transcriptional programs remain poorly understood partly because a comprehensive study of epigenetic factor expression during wound healing has not been practical. To determine which chromatin modifying factors might contribute to wound healing, we screened publicly available fluorescently-tagged reporter lines in Drosophila for altered expression at the wound periphery during healing. Thirteen reporters tagging seven different proteins showed strongly diminished expression at the wound edge. Three downregulated proteins, Osa, Kismet, and Spt6, are generally associated with active chromatin, while four others, Sin3A, Sap130, Mi-2, and Mip120, are associated with repressed chromatin. In all cases reporter down regulation was independent of the Jun N-terminal Kinase and Pvr pathways, suggesting that novel signals control reporter clearance. Taken together, our results suggest that clearance of chromatin modifying factors may enable wound edge cells to rapidly and comprehensively change their transcriptional state following tissue damage. PMID- 25114798 TI - Donor Heart Utilization following Cardiopulmonary Arrest and Resuscitation: Influence of Donor Characteristics and Wait Times in Transplant Regions. AB - Background. Procurement of hearts from cardiopulmonary arrest and resuscitated (CPR) donors for transplantation is suboptimal. We studied the influences of donor factors and regional wait times on CPR donor heart utilization. Methods. From UNOS database (1998 to 2012), we identified 44,744 heart donors, of which 4,964 (11%) received CPR. Based on procurement of heart for transplantation, CPR donors were divided into hearts procured (HP) and hearts not procured (HNP) groups. Logistic regression analysis was used to identify predictors of heart procurement. Results. Of the 4,964 CPR donors, 1,427 (28.8%) were in the HP group. Donor characteristics that favored heart procurement include younger age (25.5 +/- 15 yrs versus 39 +/- 18 yrs, P <= 0.0001), male gender (34% versus 23%, P <= 0.0001), shorter CPR duration (<15 min versus >30 min, P <= 0.0001), and head trauma (60% versus 15%). Among the 11 UNOS regions, the highest procurement was in Region 1 (37%) and the lowest in Region 3 (24%). Regional transplant volumes and median waiting times did not influence heart procurement rates. Conclusions. Only 28.8% of CPR donor hearts were procured for transplantation. Factors favoring heart procurement include younger age, male gender, short CPR duration, and traumatic head injury. Heart procurement varied by region but not by transplant volumes or wait times. PMID- 25114799 TI - Intravitreal bevacizumab alone or combined with macular laser photocoagulation for recurrent or persistent macular edema secondary to branch retinal vein occlusion. AB - Background. To evaluate the efficacy of intravitreal bevacizumab (IVB) injection with or without macular laser photocoagulation (MLP) for recurrent or persistent macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods. Thirty-four eyes underwent IVB injection for ME secondary to BRVO as a primary treatment. Twenty of the 34 eyes experienced recurrent or persistent ME after the first IVB. Nine of the 20 eyes (Group 1) were retreated with IVB combined with MLP. The remaining 11 eyes (Group 2) were retreated with IVB alone. Results. In Group 1, the postoperative best corrected visual acuity (BCVA) improved compared with the preoperative value at all follow-up visits, although no statistically significant improvement was observed at 6 months. In contrast, BCVA significantly improved from 0.53 to 0.40 at 6 months (P < 0.05) in Group 2. Conclusion. Combined therapy tended to have a smaller effect on visual acuity compared with IVB monotherapy. PMID- 25114800 TI - The trajectory and the related physical and social determinants of body mass index in elementary school children: results from the child and adolescent behaviors in long-term evolution study. AB - This study explored developmental trajectory patterns of BMI and associated factors. Participants included 1,609 students who were followed from age 7 to 12 years. Data collection involved annual self-administered questionnaires and records of height and weight. An ecological model was used to identify the factors associated with BMI trajectories. Group-based trajectory models and multinomial logit models were used in the statistical analysis. There were gender differences in BMI trajectories. Among boys, four BMI trajectories were normal or slightly underweight, persistently normal weight, overweight becoming obese, and persistently obese. Among girls, four BMI trajectories were persistently slightly underweight, persistently normal weight, persistently overweight, and persistently obese. The mean BMI in each trajectory group demonstrated an upward trend over time. In boys, BMI trajectories were significantly associated with after-school exercise, academic performance, family interactions, overweight parents, and father's education level. In girls, BMI trajectories were significantly associated with television viewing or computer use, family interactions, peer interactions, and overweight parents. Children under age 7 years who are already overweight or obese are an important target for interventions. The different factors associated with BMI trajectories can be used for targeting high risk groups. PMID- 25114802 TI - Biologic collagen cylinder with skate flap technique for nipple reconstruction. AB - A surgical technique using local tissue skate flaps combined with cylinders made from a naturally derived biomaterial has been used effectively for nipple reconstruction. A retrospective review of patients who underwent nipple reconstruction using this technique was performed. Comorbidities and type of breast reconstruction were collected. Outcome evaluation included complications, surgical revisions, and nipple projection. There were 115 skate flap reconstructions performed in 83 patients between July 2009 and January 2013. Patients ranged from 32 to 73 years old. Average body mass index was 28.0. The most common comorbidities were hypertension (39.8%) and smoking (16.9%). After breast reconstruction, 68.7% of the patients underwent chemotherapy and 20.5% underwent radiation. Seventy-one patients had immediate breast reconstruction with expanders and 12 had delayed reconstruction. The only reported complications were extrusions (3.5%). Six nipples (5.2%) in 5 patients required surgical revision due to loss of projection; two patients had minor loss of projection but did not require surgical revision. Nipple projection at time of surgery ranged from 6 to 7 mm and average projection at 6 months was 3-5 mm. A surgical technique for nipple reconstruction using a skate flap with a graft material is described. Complications are infrequent and short-term projection measurements are encouraging. PMID- 25114801 TI - Exploration of the Effect of Tobacco Smoking on Metabolic Measures in Young People Living with HIV. AB - We conducted cross-sectional, multicenter studies in HIV-positive young women and men to assess metabolic and morphologic complications from tobacco smoking in 372 behaviorally infected HIV-positive youth, aged 14-25 years. Measurements included self-reported tobacco use, fasting lipids, glucose, fat distribution, and bone mineral density (BMD; dual-energy X-ray absorptiometry scans). Overall, 144 (38.7%) self-reported smoking tobacco and 69 (47.9%) of these reported smoking greater than five cigarettes per day. Smokers versus nonsmokers had lower mean total cholesterol (146.0 versus 156.1 mg/dL; P < 0.01) and lower mean total body fat percent (24.1% versus 27.2%, P = 0.03). There was no difference between smokers and nonsmokers in fasting glucose or BMD. There appear to be only minimal effects from tobacco smoking on markers of cardiac risk and bone health in this population of HIV-positive youth. While these smokers may not have had sufficient exposure to tobacco to detect changes in the outcome measures, given the long term risks associated with smoking and HIV, it is critical that we encourage HIV positive youth smokers to quit before the deleterious effects become apparent. PMID- 25114803 TI - Tsc2 Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during Gestational Immune Activation. AB - Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of syndromic autism, such as autism associated with tuberous sclerosis, a genetic disorder caused by heterozygous TSC1 or TSC2 mutations. Environmental risk factors, such as gestational viral infections, may, in some cases, also contribute to the pathogenesis of autism and related neuropsychiatric disorders. We have recently found that a heterozygous Tsc2 mutation and the poly I:C model of maternal immune activation (MIA) interactively perturb fetal development and adult social behavior in mice, suggesting that these factors converge on shared pathways. TSC/mTOR signaling plays an important role in the modulation of immune responses, raising the possibility that the damage caused by MIA was greater in Tsc2(+/-) than in wildtype fetuses because of an exacerbated immune response in the mutants. Here, cytokine antibody arrays were employed to measure relative cytokine abundances in the fetal brain and the placenta during MIA. Cytokines were induced by gestational poly I:C but there was no obvious modulatory effect of Tsc2 haploinsufficiency. The data indicate that cytokine exposure during MIA is comparable in Tsc2 haploinsufficient and wildtype control fetuses, suggesting that downstream molecular and cellular processes may account for the interactive effects of Tsc2 haploinsufficiency and MIA. PMID- 25114804 TI - Lifestyle and Dietary Behaviors among Saudi Preschool Children Attending Primary Health Care Centers, Eastern Saudi Arabia. AB - Objective. To study life styles and dietary behaviors among Saudi preschool children (1-5 years) attending primary health care centers (PHCCs) in Dammam and Qatif areas, eastern province, Saudi Arabia. Material and Methods. Cross sectional study. Data were collected using structured, interviewer-filled questionnaire. Children and their mothers were encountered during their well-baby clinic visits. A total number of 300 preschool children and their mothers were interviewed during study period. Results. Unsatisfactory areas include smoking fathers (32%), smoking in front of children (11.3%), overweight and obesity among mothers (60.3%), noncompliance using seat belts for both parents (56.3%) and children (68%), children watching television (T.V) more than 2 hours (50%), adherence to exclusive breast feeding (only 20.7%), and late solid food introduction (65.3%). Frequent intake of unhealthy food items was 26%, 25%, and 24% for pizza, burger, and soft drinks. Unfortunately frequent intake of the following unhealthy food items was high: biscuits, deserts/chocolates, and chips which was 78%, 67%, and 72%, respectively. Conclusion. This study provides benchmark about the current situation. It provides health care workers and decision makers with important information that may help to improve health services. PMID- 25114805 TI - Emergency sonography AIDS diagnostic accuracy of torso injuries: a study in a resource limited setting. AB - Introduction. Clinical evaluation of patients with torso trauma is often a diagnostic challenge. Extended focused assessment with sonography for trauma (EFAST) is an emergency ultrasound scan that adds to the evaluation of intrathoracic abdominal and pericardial cavities done in FAST (focused assessment with sonography for trauma). Objective. This study compares EFAST (the index test) with the routine standard of care (SoC) investigations (the standard reference test) for torso trauma injuries. Methods. A cross-sectional descriptive study was conducted over a 3-month period. Eligible patients underwent EFAST scanning and the SoC assessment. The diagnostic accuracy of EFAST was calculated using sensitivity and specificity scores. Results. We recruited 197 patients; the M : F ratio was 5 : 1, with mean age of 27 years (SD 11). The sensitivity of EFAST was 100%, the specificity was 97%, the PPV was 87%, and the NPV was 100%. It took 5 minutes on average to complete an EFAST scan. 168 (85%) patients were EFAST-scanned. Most patients (82) (48%) were discharged on the same day of hospitalization, while 7 (4%) were still at the hospital after two weeks. The mortality rate was 18 (9%). Conclusion. EFAST is a reliable method of diagnosing torso injuries in a resource limited context. PMID- 25114807 TI - Failure of ketamine anesthesia in a patient with lamotrigine overdose. AB - Introduction. It is important to know which clinical situations prevent ketamine from working. Case Report. We present the case of the psychiatric inpatient who was admitted to our emergency department after ingesting a toxic dose of lamotrigine, unknown at that time. On admission, she was clearly in distress, displaying extreme agitation and violent ataxic movements. We opted to achieve sedation using intravenous ketamine boluses. Unexpectedly, after being injected with a total of 250 mg ketamine, our patient displayed no signs of dissociative anaesthesia. Discussion. There was no apparent reason for why ketamine failed, but an interaction between lamotrigine and ketamine was suspected. A literature search was performed. Very few articles describe interactions between lamotrigine and ketamine. Experimental studies, however, demonstrate how lamotrigine attenuates the neuropsychiatric effects of ketamine. Ketamine is classically described as an NMDA antagonist. Ketamine's dissociative effects, however, are thought to be mediated by increased glutamate release via a pathway not dependent on NMDA receptors. Lamotrigine, on the other hand, is known to reduce cortical glutamate release. Conclusion. Lamotrigine reduces the glutamate release needed to mediate ketamine's dissociative anaesthesia. This is important knowledge for anaesthesiologists in the emergency room where ketamine is often administered to unstable patients. PMID- 25114806 TI - Combination of acellular nerve graft and schwann cells-like cells for rat sciatic nerve regeneration. AB - OBJECTIVE: To investigate the effect of tissue engineering nerve on repair of rat sciatic nerve defect. METHODS: Forty-five rats with defective sciatic nerve were randomly divided into three groups. Rats in group A were repaired by acellular nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In group C, rats were repaired by autogenous nerve grafts. After six and twelve weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP), histological and transmission electron microscope observation, recovery ratio of wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number, nerve fiber diameter, and thickness of the myelin sheath were measured to assess the effect. RESULTS: After six and twelve weeks, the recovery ratio of SFI and wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated nerve fibers in groups B and C were superior to that of group A (P < 0.05), and the difference between groups B and C was not statistically significant (P > 0.05). CONCLUSION: The tissue engineering nerve composed of acellular allogenic nerve scaffold and Schwann cells-like cells can effectively repair the nerve defect in rats and its effect was similar to that of the autogenous nerve grafts. PMID- 25114808 TI - CTCFL (BORIS) mRNA Expression in a Peripheral Giant Cell Granuloma of the Oral Cavity. AB - Peripheral giant cell granuloma (PGCG) is a relatively common benign reactive lesion of the oral cavity which can occur at any age. CTCFL/BORIS (CTCF like/Brother of the Regulator of Imprinted Sites) and CTCF (CCCTC-binding factor) are paralogous genes with an important role in the regulation of gene expression, genomic imprinting, and nuclear chromatin insulators regulation. BORIS expression promotes cell immortalization and growth while CTCF has tumor suppressor activity; the expression pattern may reflect the reverse transcription silencing of BORIS. The aim of this work was to describe a histopathological and molecular approach of an 8-year-old pediatric male patient with PGCG diagnosis. It was observed that the PGCG under study expressed CTCF as well as BORIS mRNAs alongside with the housekeeping gene GAPDH, which may be related to possible genetic and epigenetic changes in normal cells of oral cavity. PMID- 25114809 TI - Odontogenic keratocyst mimicking paradental cyst. AB - Objective. The aim of this paper is to present an uncommon clinical and radiographic aspect of odontogenic keratocyst (OKC) mimicking paradental cyst. Methods. A 32-year-old female patient showed a well-delimited radiolucent lesion connected with the root of the left third molar with close anatomical relationship with the mandibular canal. The clinical, radiographic, and anamnestic features lead us to diagnose a paradental cyst that was treated by enucleation after extraction of the partially impacted tooth. Results. Histological analysis showed typical histological features of PKC such as the presence of a lining of stratified squamous epithelium with a well-defined basal layer of palisading columnar of cuboidal cells. Conclusion. Initial X-ray analysis and the position of the lesion related to the third mandibular tooth caused us to mistakenly diagnose a paradental cyst. We were only able to identify the cyst as an PKC rather than a paradental cyst after histological analysis. PMID- 25114810 TI - Acute Testicular Ischemia following Endovascular Abdominal Aortic Aneurysm Repair Identified in the Emergency Department. AB - Endovascular aneurysm repair (EVAR) is perhaps the most widely utilized surgical procedure for patients with large abdominal aortic aneurysms. This procedure is minimally invasive and reduces inpatient hospitalization requirements. The case involves a 72-year-old male who presented to the emergency department with right testicular ischemia two days following EVAR. Given the minimal inpatient hospitalization associated with this procedure, emergency physicians are likely to encounter associated complications. Ischemic and thromboembolic events following EVAR are extremely rare but require prompt vascular surgery intervention to minimize morbidity and mortality. PMID- 25114812 TI - Long-Term Follow-Up of a Child with Autoimmune Thyroiditis and Recurrent Hyperthyroidism in the Absence of TSH Receptor Antibodies. AB - Hashitoxicosis is an initial, transient, hyperthyroid phase that rarely affects patients with Hashimoto thyroiditis. We present here an unusual case of a child with Hashimoto thyroiditis and recurrent hyperthyroidism. A 4 yr 6/12 old male was diagnosed by us with autoimmune subclinical hypothyroidism (normal free T4, slightly elevated TSH, and elevated TG antibody titer). Two years and 6/12 later he experienced increased appetite and poor weight gain; a laboratory evaluation revealed suppressed TSH, elevated free T4, and normal TSI titer. In addition, an I(123) thyroid uptake was borderline-low. A month later, the free T4 had normalized. After remaining asymptomatic for 3 years, the patient presented again with increased appetite, and he was found with low TSH and high free T4. Within the following 3 months, his free T4 and TSH normalized. At his most recent evaluation, his TSH was normal and the free T4 was borderline-high; the TG antibody titer was still elevated and the TSI titer was negative. To our knowledge, this is the first patient reported with Hashimoto thyroiditis and recurrent hyperthyroidism. This case exemplifies the variability of the manifestations and natural history of Hashimoto thyroiditis and supports the need for a long-term evaluation of patients with autoimmune thyroid disease. PMID- 25114811 TI - Pneumomediastinum in blunt chest trauma: a case report and review of the literature. AB - Blunt trauma is the most common mechanism of injury in patients with pneumomediastinum and may occur in up to 10% of patients with severe blunt thoracic and cervical trauma. In this case report we present a 24-year-old man with pneumomediastinum due to blunt chest trauma after jumping from a bridge into a river. He complained of persistent retrosternal pain with exacerbation during deep inspiration. Physical examination showed only a slight tenderness of the sternum and the extended Focused Assessment with Sonography for Trauma (e-FAST) was normal. Pneumomediastinum was suspected by chest X-ray and confirmed by computed tomography, which showed a lung contusion as probable cause of the pneumomediastinum due to the "Mackling effect." Sonographic findings consistent with pneumomediastinum, like the "air gap" sign, are helpful for quick bedside diagnosis, but the diagnostic criteria are not yet as well established as for pneumothorax. This present case shows that despite minimal findings in physical examination and a normal e-FAST a pneumomediastinum is still possible in a patient with chest pain after blunt chest trauma. Therefore, pneumomediastinum should always be considered to prevent missing major aerodigestive injuries, which can be associated with a high mortality rate. PMID- 25114813 TI - Novel Mutation in the PKHD1 Gene Diagnosed Prenatally in a Fetus with Autosomal Recessive Polycystic Kidney Disease. AB - We report a 29-year-old gravida 2, para 0100, who presented at 19 weeks and 4 days of gestation for ultrasound to assess fetal anatomy. Routine midtrimester fetal anatomy ultrasound revealed enlarged, hyperechoic fetal kidneys and normal amniotic fluid index. Follow-up ultrasound at 23 weeks and 5 days revealed persistently enlarged, hyperechoic fetal kidneys. Progressive oligohydramnios was not evident until 29 weeks of gestation, with anhydramnios noted by 35 weeks of gestation. Amniocentesis was performed for karyotype and to search for mutations in the PKHD1 for the presumptive diagnosis of autosomal recessive polycystic kidney disease (ARPKD). In our patient, a maternally inherited, previously reported pathogenic missense mutation in the PKHD1 gene, c.10444C>T, was identified. A second, previously unreported de novo mutation, c.5909-2delA, was also identified. This mutation affects the canonical splice site and is most likely pathogenic. Our case highlights PKHD1 allelic heterogeneity and the importance of genetic testing in the prenatal setting where many other genetic etiologies can phenocopy ARPKD. PMID- 25114814 TI - Failure of Recombinant Activated Factor VII in Treatment of Diffuse Alveolar Hemorrhage due to Cryoglobulinemic Vasculitis. AB - Diffuse alveolar hemorrhage (DAH) is a serious complication of the small vessel vasculitis syndromes and carries a high mortality. Recombinant activated factor VII (rFVIIa) is used to treat bleeding in patients with hemophilia and antibodies to factor VIII or IX. It is increasingly being used in life-threatening hemorrhage in a variety of other settings in which conventional therapy is unsuccessful. Randomized controlled trials of rFVIIa in DAH are lacking. However, several case reports have described a complete or sustained control of DAH using rFVIIa after patients failed to respond to medical treatment. There are no case reports in the literature describing the use or the failure of rFVIIa in DAH associated with cryoglobulinemic vasculitis. We here report the failure of rFVIIa to control DAH in a patient with CD5+ B-cell non-Hodgkin's lymphoma and cryoglobulinemic vasculitis. PMID- 25114815 TI - Disseminated abdominal hydatidosis: a rare presentation of common infectious disease. AB - Hydatid disease is one of the most geographically widespread zoonoses with substantial disease burden. In this report we are discussing an unusual case of intra-abdominal HD that was ongoing for 22 years despite two surgical interventions. Significant symptomatic relief was achieved within the first two months of combination therapy with albendazole and praziquantel. HD is still of public health concern in the Middle East that needs optimized care. PMID- 25114816 TI - Chryseobacterium indologenes Septicemia in an Infant. AB - Chryseobacterium indologenes is a rare cause of infection in children. The organism causes infections mostly in hospitalised patients with severe underlying diseases. The choice of an effective drug for the treatment of infections due to C. indologenes is difficult as the organism has a limited spectrum of antimicrobial sensitivity. We present a case of nosocomial septicemia caused by C. indologenes in an infant with congenital heart disease who was successfully treated with trimethoprim sulfamethoxazole and also reviewed fourteen additional cases of C. indologenes infections reported in the English literature in this report. PMID- 25114817 TI - Subphrenic abscess as a complication of hemodialysis catheter-related infection. AB - We describe an unusual case of subphrenic abscess complicating a central venous catheter infection caused by Pseudomonas aeruginosa in a 59-year-old woman undergoing hemodialysis. The diagnosis was made through computed tomography, and Pseudomonas aeruginosa was isolated from the purulent drainage of the subphrenic abscess, the catheter tip and exit site, and the blood culture samples. A transesophageal echocardiography showed a large tubular thrombus in superior vena cava, extending to the right atrium, but no evidence of endocarditis or other metastatic infectious foci. Catheter removal, percutaneous abscess drainage, anticoagulation, and antibiotics resulted in a favourable outcome. PMID- 25114818 TI - Concurrent Malignant Solitary Fibrous Tumor Arising from the Omentum and Grade 3 Endometrial Endometrioid Adenocarcinoma of the Uterus with p53 Immunoreactivity. AB - A malignant solitary fibrous tumor arising from the omentum is extremely rare. To our knowledge, this is the first case of a malignant solitary fibrous omentum tumor coexisting with uterine corpus cancer. A 62-year-old woman presented to our hospital with vaginal discharge. Endometrioid adenocarcinoma was diagnosed by endometrial curettage. In addition, a solid tumor in front of the uterus was detected following computed tomography and/or magnetic resonance imaging, which was suspected to be a primary (or secondary) malignant tumor arising from the omentum. Hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymphadenectomy were performed. A malignant solitary fibrous tumor of the omentum and grade 3 endometrioid adenocarcinoma of the uterus were diagnosed by pathohistological analysis. Interestingly, the tumor cells were immunoreactive for p53. Adjuvant chemotherapy was administered for the uterine corpus cancer and the patient remains healthy 48 months after the surgery. These tumors may have become malignant due to the presence of p53 mutations. PMID- 25114819 TI - Spontaneous Hemoperitoneum due to Rupture of Uterine Varicose Veins during Labor Successfully Treated by Percutaneous Embolization. AB - Hemoperitoneum during pregnancy is a rare but potentially lethal clinical condition. Improvements in antenatal and intrapartum care, especially in surgical and anesthetic techniques, have reduced maternal mortality; perinatal mortality remains very high (31%). Treatment is based on the systemic correction of hypovolemia and immediate surgery via laparotomy or laparoscopy in cases in the first trimester of pregnancy for hemostatic purposes. Sometimes, hysterectomy is needed. A 35-year-old Asiatic primigravid woman at 37 weeks' gestation with otherwise uneventful pregnancy came to the hospital referring abrupt-onset lumbar and abdominal pain. A bleeding uterine superficial varicocele of about 7 cm was found on the left uterine horn during Caesarean section. Interventional radiologic embolization of both uterine arteries was successfully performed. Posterior evolution of the patient was favorable. Percutaneous vascular embolization of the uterine arteries is an effective alternative treatment for many obstetrical and gynecological causes of bleeding. The main advantage of this technique is the low rate of serious complications and the preservation of reproductive function. To our knowledge, this is the first case of spontaneous intrapartum hemoperitoneum treated with this technique. An early diagnosis and a rapid indication of this therapeutic option are essential. Hemodynamic stability is needed to decide this conservative management. PMID- 25114820 TI - Retracted: Intravenous leiomyoma with extension to the heart: a case report and review of the literature. PMID- 25114821 TI - Malignant mesenteric perivascular epithelioid cell neoplasm presenting as an intra-abdominal fistula in a 49-year-old female. AB - Perivascular epithelioid cell tumors are rare mesenchymal tumors arising from histologically and immunohistochemically distinctive perivascular epithelioid cells that express both myogenic and melanocytic markers. These tumors are known to arise from different organs in the body and usually have an unpredictable clinical course. We report a case of a 49-year-old female who presented with diffuse abdominal pain, fever, chills, and nonbilious vomiting for a day. Work-up revealed a mesenteric mass measuring 13.5 * 7.7 * 9.5 cm, arising in the mesentery of the hepatic flexure, with adjacent gas suggestive of fistularization into the right colon. An exploratory laparotomy with resection of the mesenteric mass was performed, and the initial histopathology results were compatible with either an adenocarcinoma or a sarcoma; however, because of poor differentiation it was difficult to make a definitive diagnosis. However, final histopathology results revealed a malignant perivascular epithelioid cell tumor (with reservation that a S100 negative metastatic melanoma must be excluded clinically). Following surgery the patient was started on everolimus, an m-TOR inhibitor, and has shown good response to this medication. PMID- 25114822 TI - Bioabsorbable suture anchor migration to the acromioclavicular joint: how far can these implants go? AB - Few complications regarding the use of bioabsorbable suture anchors in the shoulder have been reported. What motivated this case report was the unusual location of the anchor, found in the acromioclavicular joint which, to our knowledge, has never been reported so far. A 53-year old male with previous rotator cuff (RC) repair using bioabsorbable suture anchors presented with pain and weakness after 2 years of surgery. A suspicion of retear of the RC led to request of a magnetic resonance image, in which the implant was found located in the acromioclavicular joint. The complications reported with the use of metallic implants around the shoulder led to the development of bioabsorbable anchors. Advantages are their absorption over time, minimizing the risk of migration or interference with revision surgery, less artifacts with magnetic resonance imaging, and tendon-to-bone repair strength similar to metallic anchors. Since the use of bioabsorbable suture anchors is increasing, it is important to know the possible complications associated with these devices. PMID- 25114823 TI - Solitary fibrous tumor of the lumbar spine: the great mimicker-report of the fifth case. AB - Solitary fibrous tumor (SFT) is a rare neoplasm occurring in the central nervous system. It rarely occurs in the spine. This paper reports the fifth case of SFT in a 34-year-old female and focusses on differential diagnosis and importance of surgical treatment. PMID- 25114824 TI - Invasive mucinous adenocarcinoma associated with adjacent sessile serrated lesion of the appendix vermiform: a case report. AB - Although the definition of sessile serrated lesion (SSL) of colon is controversial and the risk of progression to malignancy is also under investigation at present, SSL is generally described as a polyp characterized by a serrated architecture. It is estimated to represent a feature of a new cancerization pathway, coined "serrated neoplasia pathway," particularly in right sided colon adenocarcinomas. On the other hand, in appendix, the role of this pathway remains uncertain, probably because very few cases of appendiceal adenocarcinoma associated with SSL were reported, and furthermore, immunohistochemical examination was rarely carried out. We herein report an interesting case of invasive appendiceal mucinous adenocarcinoma exhibiting SSL, which was pathologically estimated as a potential precursor lesion, and performed representative immunohistochemistry for both the mucinous adenocarcinoma and SSL in the same specimen. To further elucidate the progression of the appendiceal carcinoma from SSL, both an adequate sectioning of the lesion and systematic immunohistochemical examination of a large number of appendiceal carcinoma cases containing adjacent SSL would be required. PMID- 25114825 TI - Perilobar nephroblastomatosis: natural history and management. AB - Nephroblastomatosis (NB) has been considered as a precursor of Wilms tumor (WT). The natural history of NB seems to present significant variation as some lesions may regress spontaneously, while others may grow and expand or relapse and develop into WT later in childhood. Although, most investigators suggest adjutant chemotherapy, the effect and duration of treatment are not well established. Children with diffuse perilobar NB, Beckwith-Wiedemann syndrome, and hemihypertrophy seem to particularly benefit from treatment. We discuss our experience on two cases of NB and we review the literature for the management of this rare condition. PMID- 25114826 TI - Immunosuppressant-associated neurotoxicity responding to olanzapine. AB - Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance. PMID- 25114827 TI - Treatment of anxiety and depression in a patient with brugada syndrome. AB - Background. Brugada syndrome is rare and has been a clinically diagnosable entity since 1992. Its clinical manifestations are highly variable, and while some patients remain asymptomatic, others endure sudden cardiac death. Initial presenting symptoms may include palpitations, seizures, syncope, and nocturnal agonal respiration. The diagnosis of Brugada syndrome relies on both clinical findings and characteristic ECG patterns that occur spontaneously or are induced by usage of sodium-channel blocking agents. Aims of Case Report. Many psychiatrists may be unaware of the possibility of medical cocontributing etiologies to physical symptoms of anxiety and depression. We present a case of a patient who was treated psychiatrically for anxiety and panic attacks and who was subsequently diagnosed with Brugada syndrome and treated medically with an implantable cardioverter defibrillator (ICD), the only treatment option demonstrated to be effective. Her psychiatric symptoms predated her diagnosis of Brugada syndrome by at least fifteen years. Conclusion. The patient's eventual diagnosis of Brugada syndrome altered the course of her psychopharmacologic medication management and illustrates the utility of a psychosomatic approach to psychiatric symptom management. PMID- 25114828 TI - Response to rituximab in a case of lupus associated digital ischemia. AB - We report the case of a 38-year-old female patient with systemic lupus erythematosus (SLE) and Jaccoud arthritis (JA) that sequentially developed digital ischemic lesions of the hands. In spite of follow-up treatment with glucocorticoids, immunosuppressant, antiaggregant, and potent vasodilatator agents, a serious progression to digital gangrene over a one-month period was observed. Surprisingly, her nonhealing digital lesions improved after two cycles of rituximab (RTX) administration. PMID- 25114830 TI - Notch and TGFbeta: Functional partners facilitating tumor progression. AB - Cell signals integral to the tumor microenvironment influence cancer progression. Tumor-associated myeloid cells secrete pro-tumorigenic agents including, but not limited to, the potent cytokine transforming growth factor beta (TGFbeta). We have discovered a network of extrinsic signals including delta-like 4 (Dll4), Notch and TGFbeta, linking malignant cells and tumor-infiltrating myeloid cells, a nexus portending a clinically-relevant anticancer treatment. PMID- 25114829 TI - The methodological quality of animal research in critical care: the public face of science. AB - BACKGROUND: Animal research (AR) findings often do not translate to humans; one potential reason is the poor methodological quality of AR. We aimed to determine this quality of AR reported in critical care journals. METHODS: All AR published from January to June 2012 in three high-impact critical care journals were reviewed. A case report form and instruction manual with clear definitions were created, based on published recommendations, including the ARRIVE guidelines. Data were analyzed with descriptive statistics. RESULTS: Seventy-seven AR publications were reviewed. Our primary outcome (animal strain, sex, and weight or age described) was reported in 52 (68%; 95% confidence interval, 56% to 77%). Of the 77 publications, 47 (61%) reported randomization; of these, 3 (6%) reported allocation concealment, and 1 (2%) the randomization procedure. Of the 77 publications, 31 (40%) reported some type of blinding; of these, disease induction (2, 7%), intervention (7, 23%), and/or subjective outcomes (17, 55%) were blinded. A sample size calculation was reported in 4/77 (5%). Animal numbers were missing in the Methods section in 16 (21%) publications; when stated, the median was 32 (range 6 to 320; interquartile range, 21 to 70). Extra animals used were mentioned in the Results section in 31 (40%) publications; this number was unclear in 23 (74%), and >100 for 12 (16%). When reporting most outcomes, numbers with denominators were given in 35 (45%), with no unaccounted numbers in 24 (31%), and no animals excluded from analysis in 20 (26%). Most (49, 64%) studies reported >40, and another 19 (25%) reported 21 to 40 statistical comparisons. Internal validity limitations were discussed in 7 (9%), and external validity (to humans) discussed in 71 (92%), most with no (30, 42%) or only a vague (9, 13%) limitation to this external validity mentioned. CONCLUSIONS: The reported methodological quality of AR was poor. Unless the quality of AR significantly improves, the practice may be in serious jeopardy of losing public support. PMID- 25114831 TI - Tumor-associated autoantibodies correlate with poor outcome in prostate cancer patients treated with androgen deprivation and external beam radiation therapy. AB - Standard cancer treatments trigger immune responses that may influence tumor control. The nature of these responses varies depending on the tumor and the treatment modality. We previously reported that radiation and androgen deprivation therapy (ADT) induce tumor-associated autoantibody responses in prostate cancer patients. This follow-up analysis was conducted to assess the relationship between autoantibody responses and clinical outcome. Patients with non-metastatic prostate cancer received external beam radiation therapy (EBRT) plus neoadjuvant and concurrent androgen deprivation. Treatment-induced autoantibodies were detected in almost a third of patients receiving combinatorial ADT and EBRT. Unexpectedly, patients that developed autoantibody responses to tumor antigens had a significantly lower 5-year biochemical failure free survival (BFFS) than patients that did not develop an autoantibody response. Thus, tumor-reactive autoantibodies may be associated with increased risk of biochemical failure and immunomodulation to prevent autoantibody development may improve BFFS for select, high-risk prostate cancer patients receiving both ADT and EBRT. PMID- 25114833 TI - Targeting COX-2 abrogates mammary tumorigenesis: Breaking cancer-associated suppression of immunosurveillance. AB - Three studies addressed the role of cyclooxygenase-2 (COX-2) in mammary tumorigenesis using epithelial and macrophage COX-2 knockout mice. Deletion of COX-2 in either cell restored, at least partially, tumor immunosurveillance either by changing macrophage function to offset pro-tumor effects, or by attracting more cytotoxic T lymphocytes and natural killer cells to the tumor. These studies suggest benefits from targeted COX-2 selective inhibition in combination with immunotherapies. PMID- 25114832 TI - STING-dependent cytosolic DNA sensor pathways regulate NKG2D ligand expression. AB - The DNA damage response (DDR) upregulates the expression of NKG2D ligands (NKG2DLs).1,2 We have recently reported that the DDR also induces the presence of cytosolic DNA in B-cell lymphoma cells, which leads to the activation of STING dependent cytosolic DNA sensor pathways and the expression of RAE-1 ligands for NKG2D.3. PMID- 25114834 TI - Linking tumor hypoxia with VEGFR2 signaling and compensatory angiogenesis: Glycans make the difference. AB - Although blocking vascular endothelial growth factor (VEGF) signaling is clinically beneficial in certain cancers, tumor regrowth in treated patients suggests that compensatory angiogenic programs may limit the efficacy of anti VEGF treatment. We found that association of galectin-1 with complex N-glycans on VEGFR2 links tumor hypoxia to VEGFR2 signaling and preserves angiogenesis in response to VEGF blockade. PMID- 25114835 TI - The fatal alliance of cancer and T cells: How pancreatic tumor cells gather immunosuppressive T cells. AB - Immune evasion is a hallmark of cancer. We recently identified the adhesion molecule L1CAM as biomarker of pancreatic ductal adenocarcinoma (PDAC) associated with poor prognosis. During inflammation-associated carcinogenesis, L1CAM drives the enrichment of highly immunosuppressive CD4+CD25-CD69+ T cells. Thus, L1CAM may serve as a target in immunomodulatory therapy for PDAC. PMID- 25114836 TI - Adaptation and fatigue model for neuron networks and large time asymptotics in a nonlinear fragmentation equation. AB - Motivated by a model for neural networks with adaptation and fatigue, we study a conservative fragmentation equation that describes the density probability of neurons with an elapsed time s after its last discharge. In the linear setting, we extend an argument by Laurencot and Perthame to prove exponential decay to the steady state. This extension allows us to handle coefficients that have a large variation rather than constant coefficients. In another extension of the argument, we treat a weakly nonlinear case and prove total desynchronization in the network. For greater nonlinearities, we present a numerical study of the impact of the fragmentation term on the appearance of synchronization of neurons in the network using two "extreme" cases. Mathematics Subject Classification (2000)2010: 35B40, 35F20, 35R09, 92B20. PMID- 25114838 TI - Towards optimal treatment of ductal carcinoma in situ. AB - Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer with a variable biological behavior which is difficult to accurately predict using the current clinico-pathological parameters. Randomized controlled trials have demonstrated that adjuvant radiotherapy (RT) reduces the risk of local recurrence after adequate local excision of DCIS. Tamoxifen may be considered as an adjuvant endocrine treatment in patients with high risk estrogen receptor positive disease. There is however a growing consensus that RT can be safely omitted in a subgroup of patients with favorable biological features in order to avoid overtreatment. The sentinel node biopsy is not routinely indicated but should be considered in women undergoing mastectomy for DCIS. The discovery of molecular signatures that accurately predict the biological behavior of this common malignancy will facilitate a personalized treatment approach in the future. PMID- 25114837 TI - Free radical derivatives formed from cyclooxygenase-catalyzed dihomo-gamma linolenic acid peroxidation can attenuate colon cancer cell growth and enhance 5 fluorouracil's cytotoxicity. AB - Dihomo-gamma-linolenic acid (DGLA) and its downstream fatty acid arachidonic acid (AA) are both nutritionally important omega-6 polyunsaturated fatty acids (omega 6s). Evidence shows that, via COX-mediated peroxidation, DGLA and its metabolites (1-series prostaglandins) are associated with anti-tumor activity, while AA and its metabolites (2-series prostaglandins) could be tightly implicated in various cancer diseases. However, it still remains a mystery why DGLA and AA possess contrasting bioactivities. Our previous studies showed that DGLA could go through an exclusive C-8 oxygenation pathway during COX-catalyzed lipid peroxidation in addition to a C-15 oxygenation pathway shared by both DGLA and AA, and that the exclusive C-8 oxygenation could lead to the production of distinct DGLA's free radical derivatives that may be correlated with DGLA's anti-proliferation activity. In the present work, we further investigate the anti-cancer effect of DGLA's free radical derivatives and their associated molecular mechanisms. Our study shows that the exclusive DGLA's free radical derivatives from C-8 oxygenation lead to cell growth inhibition, cell cycle arrest and apoptosis in the human colon cancer cell line HCA-7 colony 29, probably by up-regulating the cancer suppressor p53 and the cell cycle inhibitor p27. In addition, these exclusive radical derivatives were also able to enhance the efficacy of 5 Fluorouracil (5-FU), a widely used chemo-drug for colon cancer. For the first time, we show how DGLA's radical pathway and metabolites are associated with DGLA's anti-cancer activities and able to sensitize colon cancer cells to chemo drugs such as 5-FU. Our findings could be used to guide future development of a combined chemotherapy and dietary care strategy for colon cancer treatment. PMID- 25114841 TI - Breast cancer-related lymphedema: Symptoms, diagnosis, risk reduction, and management. AB - The global burden of breast cancer continues to increase largely because of the aging and growth of the world population. More than 1.38 million women worldwide were estimated to be diagnosed with breast cancer in 2008, accounting for 23% of all diagnosed cancers in women. Given that the 5-year survival rate for breast cancer is now 90%, experiencing breast cancer is ultimately about quality of life. Women treated for breast cancer are facing a life-time risk of developing lymphedema, a chronic condition that occurs in up to 40% of this population and negatively affects breast cancer survivors' quality of life. This review offers an insightful understanding of the condition by providing clinically relevant and evidence based knowledge regarding lymphedema symptoms, diagnosis, risk reduction, and management with the intent to inform health care professionals so that they might be better equipped to care for patients. PMID- 25114840 TI - Targeting autophagy in breast cancer. AB - Macroautophagy (referred to as autophagy here) is an intracellular degradation pathway enhanced in response to a variety of stresses and in response to nutrient deprivation. This process provides the cell with nutrients and energy by degrading aggregated and damaged proteins as well as compromised organelles. Since autophagy has been linked to diverse diseases including cancer, it has recently become a very interesting target in breast cancer treatment. Indeed, current clinical trials are trying to use chloroquine or hydroxychloroquine, alone or in combination with other drugs to inhibit autophagy during breast cancer therapy since chemotherapy and radiation, regimens that are used to treat breast cancer, are known to induce autophagy in cancer cells. Importantly, in breast cancer, autophagy has been involved in the development of resistance to chemotherapy and to anti-estrogens. Moreover, a close relationship has recently been described between autophagy and the HER2 receptor. Here, we discuss some of the recent findings relating autophagy and cancer with a particular focus on breast cancer therapy. PMID- 25114843 TI - Diagnosis and surgical management of breast cancer metastatic to the spine. AB - Breast cancer is the most common malignancy and the second leading cause of death in Western women. Breast cancer most commonly metastasizes to the bone and has a particular affinity with the spine, accounting for 2/3 of osseous metastases discovered. With significant improvements in cancer therapies, the number of patients at risk for symptomatic spinal metastases is likely to increase. Patients may suffer from intractable pain and neurological dysfunction, negatively influencing their quality of life. Timely diagnosis of patients is crucial and has been aided by several breakthrough advances in imaging techniques which aid in detection, staging, and follow-up of bone metastases. Breast metastases are usually responsive to hormonal therapy and pharmacologic interventions, but skeletal metastases often require surgical intervention. The treatments are palliative but goals include the preserving or restoring neurologic function, ensuring spinal stability, and relieving pain. Advances in surgical techniques and instrumentation have allowed more effective decompression and stabilization of the spine, and with the support of recent evidence the trend has shifted towards using more advanced surgical options in appropriately selected patients. In this review, the clinical presentation, diagnosis, patient selection, and surgical management of breast cancer metastatic to the spine are discussed. PMID- 25114842 TI - Mechanisms and therapeutic advances in the management of endocrine-resistant breast cancer. AB - The estrogen receptor (ER) pathway plays a critical role in breast cancer development and progression. Endocrine therapy targeting estrogen action is the most important systemic therapy for ER positive breast cancer. However its efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible for endocrine resistance include deregulation of the ER pathway itself, including loss of ER expression, post-translational modification of ER, deregulation of ER co-activators; increased receptor tyrosine kinase signaling leading to activation of various intracellular pathways involved in signal transduction, proliferation and cell survival, including growth factor receptor tyrosine kinases human epidermal growth factor receptor-2, epidermal growth factor receptor, PI3K/AKT/mammalian target of rapamycin (mTOR), Mitogen activated kinase (MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1 receptor; alterations in cell cycle and apoptotic machinery; Epigenetic modification including dysregulation of DNA methylation, histone modification, and nucleosome remodeling; and altered expression of specific microRNAs. Functional genomics has helped us identify a catalog of genetic and epigenetic alterations that may be exploited as potential therapeutic targets and biomarkers of response. New treatment combinations targeting ER and such oncogenic signaling pathways which block the crosstalk between these pathways have been proven effective in preclinical models. Results of recent clinical studies suggest that subsets of patients benefit from the combination of inhibitor targeting certain oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the mTOR signaling pathway, a key component implicated in mediating multiple signaling cascades, offers a promising approach to restore sensitivity to endocrine therapy in breast cancer. We systematically reviewed important publications cited in PubMed, recent abstracts from ASCO annual meetings and San Antonio Breast Cancer Symposium, and relevant trials registered at ClinicalTrials.gov. We present the molecular mechanisms contributing to endocrine resistance, in particular focusing on the biological rationale for the clinical development of novel targeted agents in endocrine resistant breast cancer. We summarize clinical trials utilizing novel strategies to overcome therapeutic resistance, highlighting the need to better identify the appropriate patients whose diseases are most likely to benefit from these specific strategies. PMID- 25114844 TI - Weight gain following breast cancer diagnosis: Implication and proposed mechanisms. AB - Weight gain occurs in the majority of women following breast cancer treatment. An overview of studies describing weight gain amongst women treated with early to modern chemotherapy regimens is included. Populations at higher risk include women who are younger, closer to ideal body weight and who have been treated with chemotherapy. Weight gain ranges between 1 to 5 kg, and may be associated with change in body composition with gain in fat mass and loss in lean body mass. Women are unlikely to return to pre-diagnosis weight. Possible mechanisms including inactivity and metabolic changes are explored. Potential interventions are reviewed including exercise, dietary changes and pharmacologic agents. Although breast cancer prognosis does not appear to be significantly impacted, weight gain has negative consequences on quality of life and overall health. Future studies should explore change in body composition, metabolism and insulin resistance. Avoiding weight gain in breast cancer survivors following initial diagnosis and treatment should be encouraged. PMID- 25114839 TI - Paraneoplastic syndromes associated with lung cancer. AB - Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or tissue damage at locations remote from the site of the primary tumor or metastases. Paraneoplastic syndromes associated with lung cancer can impair various organ functions and include neurologic, endocrine, dermatologic, rheumatologic, hematologic, and ophthalmological syndromes, as well as glomerulopathy and coagulopathy (Trousseau's syndrome). The histological type of lung cancer is generally dependent on the associated syndrome, the two most common of which are humoral hypercalcemia of malignancy in squamous cell carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in small cell lung cancer. The symptoms often precede the diagnosis of the associated lung cancer, especially when the symptoms are neurologic or dermatologic. The proposed mechanisms of paraneoplastic processes include the aberrant release of humoral mediators, such as hormones and hormone-like peptides, cytokines, and antibodies. Treating the underlying cancer is generally the most effective therapy for paraneoplastic syndromes, and treatment soon after symptom onset appears to offer the best potential for symptom improvement. In this article, we review the diagnosis, potential mechanisms, and treatments of a wide variety of paraneoplastic syndromes associated with lung cancer. PMID- 25114845 TI - Pathogenesis, prevention, diagnosis and treatment of breast cancer. AB - Breast cancer is the most common cancer affecting women worldwide. Prediction models stratify a woman's risk for developing cancer and can guide screening recommendations based on the presence of known and quantifiable hormonal, environmental, personal, or genetic risk factors. Mammography remains the mainstay breast cancer screening and detection but magnetic resonance imaging and ultrasound have become useful diagnostic adjuncts in select patient populations. The management of breast cancer has seen much refinement with increased specialization and collaboration with multidisciplinary teams that include surgeons, oncologists, radiation oncologists, nurses, geneticist, reconstructive surgeons and patients. Evidence supports a less invasive surgical approach to the staging and management of the axilla in select patients. In the era of patient/tumor specific management, the advent of molecular and genomic profiling is a paradigm shift in the treatment of a biologically heterogenous disease. PMID- 25114846 TI - Evolution of breast cancer therapeutics: Breast tumour kinase's role in breast cancer and hope for breast tumour kinase targeted therapy. AB - There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients' overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase (Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current "state of play" with respect to targeted therapy for breast cancer, as well as discussing Brk's role in the processes underlying tumour development and metastasis and its potential as a therapeutic target in breast cancer. PMID- 25114847 TI - Epithelial-mesenchymal transition transcription factors and miRNAs: "Plastic surgeons" of breast cancer. AB - Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelial-mesenchymal transition (EMT) programs in order to give cells pluripotency, leading to a stemness-like phenotype. A complete EMT would be a dead end program that would render cells unable to fully metastasize to distant organs. Evoking the EMT-mesenchymal-to-epithelial transition (MET) cascade promotes successful colonization of distal target tissues. It is unlikely that direct reprogramming or trans-differentiation without passing through a pluripotent stage would be the preferred mechanism during tumor progression. This review focuses on key EMT transcriptional regulators, EMT-transcription factors involved in EMT (TFs) and the miRNA pathway, which are deregulated in breast cancer, and discusses their implications in cancer cell plasticity. Cross regulation between EMT-TFs and miRNAs, where miRNAs act as co-repressors or co activators, appears to be a pivotal mechanism for breast cancer cells to acquire a stem cell-like state, which is implicated both in breast metastases and tumor recurrence. As a master regulator of miRNA biogenesis, the ribonuclease type III endonuclease Dicer plays a central role in EMT-TFs/miRNAs regulating networks. All these EMT-MET key regulators represent valuable new prognostic and predictive markers for breast cancer as well as promising new targets for drug-resistant breast cancers. PMID- 25114848 TI - Regulation of the mRNA half-life in breast cancer. AB - The control of the half-life of mRNA plays a central role in normal development and in disease progression. Several pathological conditions, such as breast cancer, correlate with deregulation of the half-life of mRNA encoding growth factors, oncogenes, cell cycle regulators and inflammatory cytokines that participate in cancer. Substantial stability means that a mRNA will be available for translation for a longer time, resulting in high levels of protein gene products, which may lead to prolonged responses that subsequently result in over production of cellular mediators that participate in cancer. The stability of these mRNA is regulated at the 3'UTR level by different mechanisms involving mRNA binding proteins, micro-RNA, long non-coding RNA and alternative polyadenylation. All these events are tightly inter-connected to each other and lead to steady state levels of target mRNAs. Compelling evidence also suggests that both mRNA binding proteins and regulatory RNAs which participate to mRNA half-life regulation may be useful prognostic markers in breast cancers, pointing to a potential therapeutic approach to treatment of patients with these tumors. In this review, we summarize the main mechanisms involved in the regulation of mRNA decay and discuss the possibility of its implication in breast cancer aggressiveness and the efficacy of targeted therapy. PMID- 25114849 TI - Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets. AB - Metastatic occurrence is the principal cause of death in breast cancer patients. The high osteotropism makes breast cancer the most common primary tumor type associated with metastatic bone disease. The peculiar clinical aspects associated with metastases limited to the skeletal system suggest considering these cases as a distinctive subset of metastatic patients with a better prognosis. Because bone is frequently the first metastatic site in disease relapse, it is feasible that the next improvement in therapeutic options for bone metastatic disease could be associated with an improvement of survival expectation and quality of life in breast cancer patients. Study of the molecular basis of bone remodeling and breast cancer osteotropism has allowed identification of several therapeutic candidates involved in formation and progression of bone metastases. These targets are frequently the determinants of positive feedback between the tumor and bone cells whose clinical outcome is osteolytic lesions. In this review, we discuss the physiopathologic features underlying targeted therapeutic strategies aimed at interfering with the aberrant bone remodeling associated with breast cancer metastases. PMID- 25114850 TI - Effects of psoralens as anti-tumoral agents in breast cancer cells. AB - This review examines the biological properties of coumarins, widely distributed at the highest levels in the fruit, followed by the roots, stems and leaves, by considering their beneficial effects in the prevention of some diseases and as anti-cancer agents. These compounds are well known photosensitizing drugs which have been used as pharmaceuticals for a broad number of therapeutic applications requiring cell division inhibitors. Despite this, even in the absence of ultraviolet rays they are active. The current paper mainly focuses on the effects of psoralens on human breast cancer as they are able to influence many aspects of cell behavior, such as cell growth, survival and apoptosis. In addition, analytical and pharmacological data have demonstrated that psoralens antagonize some metabolizing enzymes, affect estrogen receptor stability and counteract cell invasiveness as well as cancer drug resistance. The scientific findings summarized highlight the pleiotropic functions of phytochemical drugs, given that recently their target signals and how these are modified in the cells have been identified. The encouraging results in this field suggest that multiple modulating strategies based on coumarin drugs in combination with canonical chemotherapeutic agents or radiotherapy could be a useful approach to address the treatment of many types of cancer. PMID- 25114852 TI - Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with tamoxifen. AB - Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is one of the most frequent alleles associated with loss of enzymatic activity. The incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is present in up to 90% of all poor metabolizers within the Caucasian population. The hypothesis under question is whether the presence of one or two non functioning (null) alleles predicts an inferior outcome in postmenopausal women with breast cancer receiving adjuvant treatment with tamoxifen. The numerous existing studies investigating the association of CYP2D6 with treatment failure in breast cancer are inconsistent and give rather conflicting results. Currently, routine CYP2D6 testing among women with breast cancer is not recommended and the significance of CYP2D6 phenotype in decision making regarding the administration of tamoxifen is unclear. The present study summarizes current literature regarding clinical studies on CYP2D6*4, particularly in terms of response to tamoxifen therapy and breast cancer outcome. PMID- 25114851 TI - Main controversies in breast cancer. AB - In this article, we have reviewed available evidence for diagnosis, treatment, and follow-up in female breast cancer (BC). Into daily clinical practice some controversies are occurred. Especially, in the diagnosis field, despite the fact that the optimal age in which screening mammography should start is a subject of intense controversy, there is a shift toward the beginning at the age of 40 although it is suggested that the net benefit is small for women aged 40 to 49 years. In addition, a promising tool in BC screening seems to be breast tomosynthesis. Other tools such as 3D ultrasound and shear wave elastography (SWE) are full of optimism in BC screening although ultrasonography is not yet a first-line screening method and there is insufficient evidence to recommend the systemic use of the SWE for BC screening. As for breast magnetic resonance imaging (MRI), even if it is useful in BC detection in women who have a strong family history of BC, it is not generally recommended as a screening tool. Moreover, based on the lack of randomized clinical trials showing a benefit of presurgical breast MRI in overall survival, it's integration into breast surgical operations remains debatable. Interestingly, in contrast to fine needle aspiration, core biopsy has gained popularity in presurgical diagnosis. Furthermore, after conservative surgery in patients with positive sentinel lymph nodes, the recent tendency is the shift from axillary dissection to axillary conserving strategies. While the accuracy of sentinel lymph node after neoadjuvant chemotherapy and second BC surgery remains controversial, more time is needed for evaluation and for determining the optimal interval between the two surgeries. Additionally, in the decision between immediate or delayed breast reconstruction, there is a tendency in the immediate use. In the prevention of BC, the controversial issue between tamoxifen and raloxifene becomes clear with raloxifene be more profitable through the toxicities of tamoxifen. However, the prevention of bone metastasis with bisphosphonates is still conflicting. Last but not least, in the follow-up of BC survivors, mammography, history and physical examination are the means of an early detection of BC recurrence. ed. PMID- 25114853 TI - Significance of immunohistochemistry in breast cancer. AB - The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with (breast) cancer. The advent of molecular technology has incorporated new biomarkers along with immunohistochemical and serum biomarkers. Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently, and both as prognostic and predictive factors. Steroid hormone receptors, markers of tumour proliferation, and factors involved in angiogenesis and apoptosis are of scientific interest. In this review we will provide information on the immunohistochemical markers used in the management of breast cancer patients using available data from the literature. We consider the utility of established immunohistochemical markers, and discuss the challenges involved in integrating novel molecular markers into clinical practice. PMID- 25114854 TI - Toremifene in the treatment of breast cancer. AB - Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier (SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase III trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events and it has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits. PMID- 25114855 TI - Exercise in patients coping with breast cancer: An overview. AB - Breast cancer is the most common type of cancer in women, but fortunately has high survival rates. Many studies have been performed to investigate the effects of exercise in patients diagnosed with breast cancer. There is evidence that exercise after the diagnosis of breast cancer improves mortality, morbidity, health related quality of life, fatigue, physical functioning, muscle strength, and emotional wellbeing. Based on scientific data, breast cancer patients should be recommended to participate in rehabilitation programs including aerobic and strength training. The aim of this article is to review the recently published data on the effect of exercise in patients with breast cancer in order to present the current perspective on the topic. PMID- 25114856 TI - Biological subtypes of breast cancer: Prognostic and therapeutic implications. AB - Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors. PMID- 25114857 TI - Current role of modern radiotherapy techniques in the management of breast cancer. AB - Breast cancer is the most common type of malignancy in females. Advances in systemic therapies and radiotherapy (RT) provided long survival rates in breast cancer patients. RT has a major role in the management of breast cancer. During the past 15 years several developments took place in the field of imaging and irradiation techniques, intensity modulated RT, hypofractionation and partial breast irradiation. Currently, improvements in the RT technology allow us a subsequent decrease in the treatment-related complications such as fibrosis and long-term cardiac toxicity while improving the loco-regional control rates and cosmetic results. Thus, it is crucial that modern radiotherapy techniques should be carried out with maximum care and efficiency. Several randomized trials provided evidence for the feasibility of modern radiotherapy techniques in the management of breast cancer. However, the role of modern radiotherapy techniques in the management of breast cancer will continue to be defined by the mature results of randomized trials. Current review will provide an up-to-date evidence based data on the role of modern radiotherapy techniques in the management of breast cancer. PMID- 25114858 TI - Therapeutic options for HER-2 positive breast cancer: Perspectives and future directions. AB - During the last 15 years we have witnessed an unprecedented expansion in the drugs developed to target human epidermal growth factor receptor-2 (HER-2) positive breast cancer. Trastuzumab, pertuzumab, ado-trastuzumab emtansine and lapatinib are currently food and drug administration (FDA)-approved for the treatment of breast cancer patients with HER-2 over-expressed. However, given the amount of information gathered from years of uninterrupted clinical research, it is essential to have periodic updates that succinctly recapitulate what we have learnt over these last years and help us to apply that information in our daily practice. This review will pursue that objective. We will summarize the most relevant and updated information related to the state of the art management of HER-2 positive breast cancer in all the clinical scenarios including the adjuvant, neoadjuvant and metastatic settings. But we will also critically appraise that literature in order to highlight some key clinical concepts that should not be overlooked. Lastly, this review will also point out some of the most promising strategies that are currently being tested and may soon become available. PMID- 25114859 TI - Modification in the diet can induce beneficial effects against breast cancer. AB - The population tends to consume foods that in addition to their nutritional values can offer some benefits to their health. There are many epidemiological evidences and research studies in animal models suggesting that diet plays an important role in breast cancer prevention or progression. This review summarized some of the relevant researches about nutrition and cancer during the last years, especially in breast cancer. The analysis of probiotics and fermented products containing lactic acid bacteria in cancer prevention and/or treatment was especially discussed. It was observed that a balance of fatty acids similar to those of traditional Mediterranean diet, the consumption of fruits and vegetables, dietary fiber intake, vitamin supplementation are, along with the intake of probiotic products, the most extensively studied by the negative association to breast cancer risk. The consumption of probiotics and fermented products containing lactic acid bacteria was associated to reduce breast cancer risk in some epidemiological studies. The use of animal models showed the modulation of the host's immune response as one of the important effects associated to the benefices observed with most probiotics. However; future assays in human are very important before the medical community can accept the addition of probiotic or fermented milks containing lactic acid bacteria as supplements for cancer patients. PMID- 25114860 TI - Challenges to the early diagnosis and treatment of breast cancer in developing countries. AB - This critical review of the literature assembles and compares available data on breast cancer clinical stage, time intervals to care, and access barriers in different countries. It provides evidence that while more than 70% of breast cancer patients in most high-income countries are diagnosed in stages I and II, only 20%-50% patients in the majority of low- and middle-income countries are diagnosed in these earlier stages. Most studies in the developed world show an association between an advanced clinical stage of breast cancer and delays greater than three months between symptom discovery and treatment start. The evidence assembled in this review shows that the median of this interval is 30-48 d in high-income countries but 3-8 mo in low- and middle-income countries. The longest delays occur between the first medical consultation and the beginning of treatment, known as the provider interval. The little available evidence suggests that access barriers and quality deficiencies in cancer care are determinants of provider delay in low- and middle-income countries. Research on specific access barriers and deficiencies in quality of care for the early diagnosis and treatment of breast cancer is practically non-existent in these countries, where it is the most needed for the design of cost-effective public policies that strengthen health systems to tackle this expensive and deadly disease. PMID- 25114861 TI - Immediate nipple-areola-sparing mastectomy reconstruction: An update on oncological and reconstruction techniques. AB - Nipple-sparing mastectomy (NSM) is a safe technique in patients who are candidates for conservation breast surgery. However, there is worry concerning its oncological safety and surgical outcome in terms of postoperative complications. The authors reviewed the literature to evaluate the oncological safety, patient selection, surgical techniques, and also to identify the factors influencing postoperative outcome and complication rates. Patient selection and safety related to NSM are based on oncological and anatomical parameters. Among the main criteria, the oncological aspects include the clinical stage of breast cancer, tumor characteristics and location including small, peripherally located tumors, without multicentricity, or for prophylactic mastectomy. Surgical success depends on coordinated planning with the oncological surgeon and careful preoperative and intraoperative management. In general, the NSM reconstruction is related to autologous and alloplastic techniques and sometimes include contra lateral breast surgery. Choice of reconstructive technique following NSM requires accurate consideration of various patient related factors, including: breast volume, degree of ptosis, areola size, clinical factors, and surgeon's experience. In addition, tumor related factors include dimension, location and proximity to the nipple-areola complex. Regardless of the fact that there is no unanimity concerning the appropriate technique, the criteria are determined by the surgeon's experience and the anatomical aspects of the breast. The positive aspects of the technique utilized should include low interference with the oncological treatment, reproducibility, and long-term results. Selected patients can have safe outcomes and therefore this may be a feasible option for early breast cancer management. However, available data demonstrates that NSM can be safely performed for breast cancer treatment in selected cases. Additional studies and longer follow-up are necessary to define consistent selection criteria for NSM. PMID- 25114862 TI - Pattern response of dendritic cells in the tumor microenvironment and breast cancer. AB - Breast cancer (BC) is the most common malignant neoplasm and the cause of death by cancer among women worldwide. Its development, including malignancy grade and patient prognosis, is influenced by various mutations that occur in the tumor cell and by the immune system's status, which has a direct influence on the tumor microenvironment and, consequently, on interactions with non-tumor cells involved in the immunological response. Among the immune response cells, dendritic cells (DCs) play a key role in the induction and maintenance of anti-tumor responses owing to their unique abilities for antigen cross-presentation and promotion of the activation of specific lymphocytes that target neoplasic cells. However, the tumor microenvironment can polarize DCs, transforming them into immunosuppressive regulatory DCs, a tolerogenic phenotype which limits the activity of effector T cells and supports tumor growth and progression. Various factors and signaling pathways have been implicated in the immunosuppressive functioning of DCs in cancer, and researchers are working on resolving processes that can circumvent tumor escape and developing viable therapeutic interventions to prevent or reverse the expression of immunosuppressive DCs in the tumor microenvironment. A better understanding of the pattern of DC response in patients with BC is fundamental to the development of specific therapeutic approaches to enable DCs to function properly. Various studies examining DCs immunotherapy have demonstrated its great potential for inducing immune responses to specific antigens and thereby reversing immunosuppression and related to clinical response in patients with BC. DC-based immunotherapy research has led to immense scientific advances, both in our understanding of the anti-tumor immune response and for the treatment of these patients. PMID- 25114863 TI - Triiodothyronine and breast cancer. AB - The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol (E2) in particular is known to be an important cause for the development and progression of BC. The proliferative effect of T3 has been demonstrated in various types of cancer. In BC cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the development and progression of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of BC, studies show that thyroid status may influence the development of tumor, proliferation and metastasis. PMID- 25114864 TI - Preventing breast cancer in LMICs via screening and/or early detection: The real and the surreal. AB - To review the present status of breast cancer (BC) screening/early detection in low- and middle-income countries (LMICs) and identify the way forward, an open focused search for articles was undertaken in PubMed, Google Scholar and Google, and using a snowball technique, further articles were obtained from the reference list of initial search results. In addition, a query was put up on ResearchGate to obtain more references and find out the general opinion of experts on the topic. Experts were also personally contacted for their opinion. Breast cancer (BC) is the most common cancer in women in the world. The rise in incidence is highest in LMICs where the incidence has often been much lower than high-income countries. In spite of more women dying of cancer than pregnancy or childbirth related causes in LMICs, most of the focus and resources are devoted to maternal health. Also, the majority of women in LMICs present at late stages to a hospital to initiate treatment. A number of trials have been conducted in various LMICs regarding the use of clinical breast examination and mammography in various combinations to understand the best ways of implementing a population level screening/early detection of BC; nevertheless, more research in this area is badly needed for different LMIC specific contexts. Notably, very few LMICs have national level programs for BC prevention via screening/early detection and even stage reduction is not on the public health agenda. This is in addition to other barriers such as lack of awareness among women regarding BC and the presence of stigma, inappropriate attitudes and lack of following proper screening behavior, such as conducting breast self-examinations. The above is mixed with the apathy and lack of awareness of policy makers regarding the fact that BC prevention is much more cost-effective and humane than BC treatment. Implementation of population level programs for screening/early detection of BC, along with use of ways to improve awareness of women regarding BC, can prove critical in stemming the increasing burden of BC in LMICs. Use of newer modalities such as ultrasonography which is more suited to LMIC populations and use of mHealth for awareness creation and increasing screening compliance are much needed extra additions to the overall agenda of LMICs in preventing BC. PMID- 25114866 TI - Adjuvant chemotherapy in breast cancer: To use or not to use, the anthracyclines. AB - Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclines in the adjuvant setting for patients with breast cancer. We consulted PubMed, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review. PMID- 25114867 TI - Inflammatory breast cancer clusters: A hypothesis. AB - Cancer clusters have long been a focus of interest because of the possibility of identifying etiologic agents. Only on rare occasions, however, have such cluster investigations been successful. One major difficulty in cluster investigations, particularly in the area of breast cancer, is the long latent period. There have been a number of publications providing a discouraging picture regarding cancer cluster investigations. The possibility of learning from a cluster investigation, however, is greatly increased if the cancer involved is relatively rare and if it has a short latent period. Inflammatory breast cancer (IBC) fits these criteria and is worth pursuing because of the strong evidence that environmental factors play a major role. In this report we describe our experience with several clusters and the lessons learned which are now being utilized to improve investigation of future IBC clusters. The first IBC cluster that we evaluated was in 2000, when we were asked to investigate an apparent cluster of IBC in Castro Valley, California where three women in an office setting of 24 people were diagnosed with IBC in a ten month period from May 1999 to March 2000. Our investigation of this striking cluster did not yield a specific trigger for this cluster but it did indicate that the women involved all had at least two IBC risk factors that may well have made them susceptible to getting IBC. We are now investigating another apparent cluster in Texas and are aware of several others requiring careful consideration. We see a need for a consistent protocol for the evaluation of IBC clusters focusing on the laboratory investigation of environmental triggers, primarily infectious agents and chemical carcinogens. PMID- 25114868 TI - Pleomorphic lobular carcinoma in situ of the breast: Can the evidence guide practice? AB - The clinical significance of pleomorphic lobular carcinoma in situ (PLCIS) is a subject of controversy. As a consequence, there is a risk of providing inconsistent management to patients presenting with PLCIS. This review aims to establish whether the current guidelines for the management of PLCIS are consistent with current evidence. A systematic electronic search was performed to identify all English language articles regarding PLCIS management. The data was analysed, specifically looking at: incidence of concurrent disease, recurrence rates, long-term prognosis and PLCIS management. A search was also performed for PLCIS management guidelines for the United Kingdom, United States, Canada, Australia, Germany and pan-European. The results of the evidence analyses were compared to the guidelines in order to establish whether the recommended management is consistent with the published evidence. Nine studies (level 3-4 evidence), involving a total of 176 patients and five management guidelines (from United Kingdom, United States, Australia and pan-European) were included in the review. From the evidence, 46 of 93 (49%) patients were found to have PLCIS with concurrent invasive disease on excision specimen analysis. Regarding recurrence rates, 11 of 117 (9.4%) patients developed a recurrence of PLCIS. There were no instances of invasive disease or ductal carcinoma in situ (DCIS) on recurrence histology. There were no studies assessing long-term outcomes in PLCIS cases. With regards to the management guidelines, the Association of Breast Surgery (United Kingdom) and the National Breast and Ovarian Cancer Care (Australia) do not mention PLCIS. The National Comprehensive Cancer Network (United States) suggest considering excision of PLCIS with negative margins. The NHS Breast Screening Programme (United Kingdom) and the European Society of Medical Oncology (pan-European) recommend PLCIS should be treated as with DCIS. We conclude that high quality evidence to inform guidance is lacking, thus recommendations are relatively vague. However, based on the available evidence, it would seem prudent to treat PLCIS in a similar manner to DCIS. PMID- 25114865 TI - Green tea compounds in breast cancer prevention and treatment. AB - Breast cancer is the most common cancer among women. In recent years, many in vitro and in vivo studies indicate that green tea possesses anti-cancer effects. The epidemiological studies, however, have produced inconclusive results in humans. Likewise, results from animal models about the preventive or therapeutic effects of green tea components are inconclusive. The mechanisms by which green tea intake may influence the risk of breast cancer in humans remain elusive mechanisms by which green tea intake may influence. Here, we review recent studies of green tea polyphenols and their applications in the prevention and treatment of breast cancer. Furthermore, we discuss the effect of green tea components on breast cancer by reviewing epidemiological studies, animal model studies and clinical trials. At last, we discuss the mechanisms by which green tea components suppress the development and recurrence of breast cancer. A better understanding of the mechanisms will improve the utilization of green tea in breast cancer prevention and therapy and pave the way to novel prevention and treatment strategies for breast cancer. PMID- 25114870 TI - Subclinical hypothyroidism and pregnancy: the intersection of science, the art of medicine, and public health policy. PMID- 25114869 TI - Is exercise ignored in palliative cancer patients? AB - Exercise and rehabilitation approaches in palliative care programs for cancer patients affect patients' symptoms, physical functioning, muscle strength, emotional wellbeing, psychological symptoms, functional capacities, quality of life, mortality and morbidity positively. Based on scientific data, palliative cancer patients should be recommended to participate in exercise programs. There is no standard approach to recipe an exercise regimen for a palliative cancer survivor. Studies for demonstrating the positive effects of exercising in palliative care patients are increasing in number day by day. At this point, increasing awareness about exercising in the entire team monitoring the patient and our efforts in this matter seems to be very important. PMID- 25114872 TI - Historical note: many steps led to the 'discovery' of thyroid-stimulating hormone. AB - Finding thyroid-stimulating hormone was a process rather than a circumscribed event, and many talented persons participated over many years. Key early participants were Bennet M. Allen and Philip E. Smith who had the misfortune just prior to World War I of independently and simultaneously starting very similar experiments with tadpoles. This led to a series of back and forth publications attempting to establish priority for finding evidence of a thyrotropic factor in the anterior pituitary. Decades of work by others would be required before sophisticated biochemical techniques would bring us to our modern understanding. PMID- 25114873 TI - The TRHR Gene Is Associated with Hypothalamo-Pituitary Sensitivity to Levothyroxine. AB - BACKGROUND: Thyroidectomized patients need variable doses of levothyroxine (LT4) to obtain target thyroid-stimulating hormone (TSH) levels. Individual feedback set-points have been hypothesized and the influence of several genes in the regulation of the pituitary-thyroid axis has been demonstrated. OBJECTIVES: We hypothesized that genetic variants of the TRHR gene could be associated with a different hypothalamo-pituitary sensitivity to thyroid hormone feedback. METHODS: We retrospectively analyzed 84 thyroidectomized patients with no residual thyroid function and undetectable thyroglobulin levels. Patients were evaluated under LT4 resulting in TSH levels detectable but <0.5 MUIU/ml. The two SNPs rs3134105 and rs3110040 were identified as informative markers of the TRHR gene. Genotyping was performed using high-resolution melting technology. Genotype distribution was compared between the patients and 99 euthyroid controls. RESULTS: The selected SNPs were in linkage disequilibrium and only rs3134105 was further considered. A significant difference between the three possible genotypes for rs3134105 was found for TSH (p = 0.04) and free thyroxine (fT4)/TSH ratio (p = 0.02). Moreover, despite similar serum concentrations of free triiodothyronine (fT3) and fT4, carriers of at least one A allele of rs3134105 had significantly lower serum TSH levels (p = 0.01) as well as higher fT3/TSH (p = 0.01) and fT4/TSH ratios (p < 0.01). CONCLUSIONS: We demonstrated an association between serum TSH levels and discrete alleles of the TRHR gene in totally thyroidectomized patients under LT4 therapy. Therefore, the TRHR gene seems to be a determinant of hypothalamo pituitary sensitivity to LT4. PMID- 25114871 TI - 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. AB - This guideline has been produced as the official statement of the European Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the pregnancy-related reference range with a normal serum thyroxine concentration. Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile of the pregnancy-related reference range with a normal TSH level) is also recognized in pregnancy. In the majority of SCH the cause is autoimmune thyroiditis but may also be due to iodine deficiency. The cause of isolated hypothyroxinaemia is usually not apparent, but iodine deficiency may be a factor. SCH and isolated hypothyroxinaemia are both associated with adverse obstetric outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in isolated hypothyroxinaemia. SCH and isolated hypothyroxinaemia are both associated with neuro-intellectual impairment of the child, but there is no evidence that maternal levothyroxine therapy improves this outcome. Targeted antenatal screening for thyroid function will miss a substantial percentage of women with thyroid dysfunction. In children SCH (serum TSH concentration >5.5-10 mU/l) normalizes in >70% and persists in the majority of the remaining patients over the subsequent 5 years, but rarely worsens. There is a lack of studies examining the impact of SCH on the neuropsychological development of children under the age of 3 years. In older children, the evidence for an association between SCH and impaired neuropsychological development is inconsistent. Good quality studies examining the effect of treatment of SCH in children are lacking. PMID- 25114876 TI - Recombinant human thyrotropin use resulting in ovarian hyperstimulation: an unusual side effect. AB - A 43-year-old female was administered recombinant human thyrotropin-alpha (Thyrogen(r); Genzyme Corp., Cambridge, Mass., USA) before a fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan as part of an evaluation of thyroid cancer recurrence. She was administered two doses of Thyrogen only 4 weeks before for stimulated thyroglobulin measurement. The PET/CT scan demonstrated enlarged ovaries which on subsequent conservative follow-up resolved. This transient hyperstimulated state of the ovaries was presumed to be related to Thyrogen injections received twice within a space of a month. Thyrogen is being increasingly used for raising the level of thyroid-stimulating hormone (TSH), besides thyroid hormone withdrawal for suspected recurrence of differentiated thyroid carcinoma. Ovarian hyperstimulation has been reported as an iatrogenic complication for in vitro fertilization with the presence of human chorionic gonadotropin being invariably associated. Transient gestational thyrotoxicosis has been reported to be related to promiscuous activation of the thyrotropin receptor by chorionic gonadotropin. In our case it is possible that due to the promiscuous stimulation, thyrotropin caused a follicle-stimulating hormone (FSH)-like action resulting in ovarian hyperstimulation. The reason behind this could be the shared sequence identity of the hormone-binding domains of TSH and FSH receptors, or some mutation in the FSH receptor. In conclusion, our case highlights a potential side effect of administering Thyrogen in females of the reproductive age group. PMID- 25114874 TI - A Progress Report of the IFCC Committee for Standardization of Thyroid Function Tests. AB - BACKGROUND: The IFCC Committee for Standardization of Thyroid Function Tests aims at equivalence of laboratory test results for free thyroxine (FT4) and thyrotropin (TSH). OBJECTIVES: This report describes the phase III method comparison study with clinical samples representing a broad spectrum of thyroid disease. The objective was to expand the feasibility work and explore the impact of standardization/harmonization in the clinically relevant concentration range. METHODS: Two sets of serum samples (74 for FT4, 94 for TSH) were obtained in a clinical setting. Eight manufacturers participated in the study (with 13 FT4 and 14 TSH assays). Targets for FT4 were set by the international conventional reference measurement procedure of the IFCC; those for TSH were based on the all procedure trimmed mean. The manufacturers recalibrated their assays against these targets. RESULTS: All FT4 assays were negatively biased in the mid- to high concentration range, with a maximum interassay discrepancy of approximately 30%. However, in the low range, the maximum deviation was approximately 90%. For TSH, interassay comparability was reasonable in the mid-concentration range, but worse in the pathophysiological ranges. Recalibration was able to eliminate the interassay differences, so that the remaining dispersion of the data was nearly entirely due to within-assay random error components. The impact of recalibration on the numerical results was particularly high for FT4. CONCLUSIONS: Standardization and harmonization of FT4 and TSH measurements is feasible from a technical point of view. Because of the impact on the numerical values, the implementation needs careful preparation with the stakeholders. PMID- 25114877 TI - Simple core-needle biopsy for thyroid nodule, complicated tinnitus. AB - BACKGROUND: Fine-needle aspiration is the procedure of choice for evaluating thyroid nodules. Core-needle biopsy (CNB) is not included in the American Thyroid Association recommendations for evaluating such nodules. CNB complications are classically bleeding and hematomas. To our knowledge, no case of arteriovenous fistula (AVF) secondary to a CNB has been reported, nor has any case of tinnitus secondary to a post-CNB AVF. OBJECTIVES: To make the clinician aware of possible vascular complications caused by CNB and the possibility of difficult pathology reading caused by previous CNB. METHODS: A 44-year-old female is described who was referred to our tertiary care center for left-sided pulsatile tinnitus. She did report having had a CNB right before the tinnitus appeared. Conventional angiography demonstrated a focal AVF originating from the left vertebral artery, with reflux to the left vertebral venous plexus. A 6-mm stent was placed over the site of the fistula via an endovascular approach, which solved both the radiological and clinical documented problems. Moreover, CNB greatly complicated pathology reading once total thyroidectomy was later performed. The suspected area of invasion was an artifact due to the previous biopsies. CONCLUSION: Although many authors recommend a CNB as an alternative modality in cases of inconclusive cytology with fine-needle aspiration, it is not in the American Thyroid Association recommendations. In cases of iatrogenic AVFs caused by a CNB, angiography is recommended both as a diagnostic and therapeutic modality. Stenting the fistula with an endoprosthesis can correct the problem immediately. PMID- 25114875 TI - Development and application of a novel sensitive immunometric assay for calcitonin in a large cohort of patients with medullary and differentiated thyroid cancer, thyroid nodules, and autoimmune thyroid diseases. AB - BACKGROUND: Serum calcitonin (sCT) is a useful biomarker for medullary thyroid cancer (MTC). Consensus has not been reached concerning sCT measurements in the evaluation of nodular thyroid disease (NTD). OBJECTIVE AND METHODS: We developed a new immunofluorometric assay for sCT and have validated it in samples from 794 patients [203 with MTC, 205 with autoimmune thyroid disease (ATD), 248 with NTD, 80 with differentiated thyroid cancer (DTC) 'free of disease', 58 with chronic renal failure (CRF)] and 178 normal individuals, including samples after pentagastrin tests and samples from the washout of 92 FNA procedures in patients with NTD or MTC. We also compared some samples from patients with low or high calcitonin levels using both this assay and the Nichols Institute Diagnostics (NID) assay. RESULTS: The assay's analytical sensitivity was 1.0 pg/ml. Considering MTC patients prior to surgery, the cut-off values for the 95% reference range were 11.1 pg/ml for males and 5.5 pg/ml for females and employing the ROC curve were 18.4 pg/ml for males and 7.8 pg/ml for females. sCT in patients with MTC was strongly correlated with disease status. Patients with NTD and ATD did not present false-positive results. sCT measurements were significantly correlated with age (excluding MTC and CRF). The NID test had a strong correlation with our assay. A hook effect was observed only with concentrations >200,000 pg/ml. CONCLUSIONS: We developed a novel sCT assay and validated it in healthy subjects, as well as in a large cohort of patients with MTC, NTD, ATD, DTC, and CRF. PMID- 25114878 TI - Iodophilic synchronous phalangeal and choroidal metastasis from follicular thyroid carcinoma: a case report and review. AB - BACKGROUND: Follicular thyroid cancers constitute 15-20% of all thyroid tumors. The usual mode of dissemination is via the hematogenous route. The most common sites of distant metastasis are to the lungs and bones. OBJECTIVE: A case is presented to demonstrate the unusual presentation of follicular cancer with synchronous digital (distal phalanx of the little finger) and choroidal metastasis that was responsive to radioiodine treatment. CASE REPORT: A 54-year old female presented with swelling over the terminal part of the left little finger with thyromegaly. Investigations revealed metastasis from follicular thyroid cancer to the little finger along with pulmonary metastases. She underwent total thyroidectomy with central compartment clearance followed by (131)I therapy. Subsequent follow-up demonstrated complete regression of the digital metastasis and partial regression of the choroidal metastasis which was evaluated after the radioiodine scan that picked up the choroidal metastasis. CONCLUSION: Follicular thyroid cancers can rarely spread to unusual sites like the digits and choroid. This report highlights the synchronous presentation of digital and choroidal metastasis which responded to (131)I therapy. PMID- 25114879 TI - The Dilemma of Treating Subclinical Hypothyroidism: Risk that Current Guidelines Do More Harm than Good. PMID- 25114880 TI - Reply on the Letter by Stott et al. 'The Dilemma of Treating Subclinical Hypothyroidism: Risk that Current Guidelines Do More Harm than Good'. PMID- 25114881 TI - Letter regarding the Paper by Pearce et al. Entitled '2013 ETA Guideline: Management of Subclinical Hypothyroidism'. PMID- 25114882 TI - Diabetic foot risk factors in type 2 diabetes patients: a cross-sectional case control study. AB - BACKGROUND: Diabetic foot is a serious condition in patients with a long lasting diabetes mellitus. Diabetic foot treated improperly may lead not only to delayed ulceration healing, generalized inflammation, unnecessary surgical intervention, but also to the lower limb amputation. The aim of this study was to compare diabetic foot risk factors in population with type 2 diabetes and risk factors for diabetes in healthy subjects. METHODS: The study included 900 subjects: 145 with diabetic foot, 293 with type 2 diabetes without diabetic foot and 462 healthy controls matched in terms of mean age, gender structure and cardiovascular diseases absence. Study was conducted in Gastroenterology and Metabolic Diseases Department, Medical University of Warsaw, Poland. In statistical analysis a logistic regression model, U Mann-Whitney's and t-Student test were used. RESULTS: The binomial logit models analysis showed that the risk of diabetic foot in patients with type 2 diabetes was decreased by patient's age (odds ratio [OR] = 0.94; 95% confidence interval [CI]: 0.92-0.96; p = 0.00001) and hyperlipidaemia (OR = 0.54; 95% CI: 0.36-0.81; p = 0.01). In contrast, male gender (OR = 2.83; 95% CI: 1.86-4.28; p = 0.00001) diabetes duration (OR = 1.04; 95% CI: 1.03-1.06; p = 0.0003), weight (OR = 1.04; 95% CI: 1.03-1.06; p = 0.00001), height (OR = 1.08; 95% CI: 1.05-1.11; p = 0.00001) and waist circumference (OR = 1.028; 95% CI: 1.007-1.050; p = 0.006) increase the risk of diabetic foot. The onset of type 2 diabetes in healthy subjects was increased by weight (OR = 1.035; 95% CI: 1.024-1.046; p = 0.00001), WC (OR = 1.075; 95% CI: 1.055-1.096; p = 00001), hip circumference (OR = 1.03; 95% CI: 1.01-1.05; p = 0.005), overweight defined with body mass index (BMI) above 24,9 kg/m(2) (OR = 2.49; 95% CI: 1.77-3.51; p = 0.00001) and hyperlipidaemia (OR = 3.53; 95% CI: 2.57-4.84; p = 0.00001). CONCLUSIONS: Risk factors for Type 2 diabetes and diabetic foot are only partially common. Study proved that patients who are prone to developing diabetic foot experience different risk factors than patients who are at risk of diabetes. Identification of relationship between diabetic foot and diabetes risk factors in appropriate groups may help clinicians to focus on certain factors in diabetic foot prevention. PMID- 25114883 TI - Effects of glucose concentration in the medium on rat hepatocyte culture. AB - PURPOSE: To determine the optimum culture conditions by investigating isolated rat hepatocytes cultured in medium containing different glucose concentrations. METHODS: Hepatocytes were isolated from rats using a two-step perfusion technique and divided into the following two groups cultured in medium containing different glucose concentrations: (1) low-glucose group and (2) high-glucose group. Total cell count and viability of cultured rat hepatocytes and liver function parameters (i.e., concentrations of albumin, ammonia, and urea in the culture medium) were measured. The morphology of cultured rat hepatocytes was examined by staining with hematoxylin and eosin, and albumin receptor expression was confirmed by immunofluorescence. RESULTS: Total cell count and viability showed smaller increases in the low-glucose group than the high-glucose group, although the difference was not statistically significant (P = 0.112 and P = 0.147, respectively). The levels of albumin (P = 0.943), ammonia (P = 0.744), and urea (P = 0.709) were not significantly different between the two groups. In both groups, the function of cultured hepatocytes decreased significantly over time. The morphology of hepatocytes was well maintained in both groups at 3 days. On day 7, the cytoplasm was transformed into a spindle shape. On day 10, these changes were exaggerated, and were more prominent in the high-glucose group. CONCLUSION: Morphological assessment indicated that low-glucose culture medium is better than high-glucose culture medium for culturing of hepatocytes, although there was not significantly different in functional assessment. The cultured hepatocytes with low-glucose culture medium could be maintained for 7 days. PMID- 25114884 TI - Long-term outcomes of intraoperative and perioperative albendazole treatment in hepatic hydatidosis: single center experience. AB - PURPOSE: The aim of this study was to evaluate long-term outcome of the intraoperative and perioperative albendazole (ALB) treatment on the recurrence and/or secondary hydatidosis. METHODS: One hundred and one patients with hepatic hydatidosis were treated intraoperatively and perioperatively with ALB, in addition to surgery. Perioperative ALB treatment was given in a dose of 12-15 mg/kg/day. The ALB treatment was started 13.27 +/- 14.34 days before the surgery, and it was continued for 4.39 +/- 3.11 months postoperatively. A total of 1.7 ug/mL of ALB solution was used as a protoscolidal agent. The follow-up period was 134.55 +/- 51.56 months. RESULTS: Four patients died, with only one death was secondary to hydatid disease (cerebral eccinococcus). There was only one recurrence (1%) of hepatic hydatidosis. Early and late morbidity rates were 8.91% and 7.92%, respectively. CONCLUSION: Our results suggest that intraoperative and perioperative ALB is effective for the prevention of hepatic hydatidosis recurrence and/or secondary hydatidosis. PMID- 25114885 TI - Rationale and surgical technique of laparoscopic left lateral sectionectomy using endoscopic staples. AB - PURPOSE: Laparoscopic left lateral sectionectomy (LLLS) has been widely accepted due to benefits of minimally invasive surgery. Some surgeons prefer to isolate glissonian pedicles to segments II and III and to control individual pedicles with surgical clips, whereas opt like to control glissonian pedicles simultaneously using endoscopic stapling devices. The aim of this study was to find the rationale of LLLS using endoscopic staples. METHODS: We retrospectively analyzed and compared the clinical outcomes (operation time, drainage length, transfusion, hospital stay, and complication rate) of 35 patients that underwent LLLS between April 2004 and February 2012. Patients were dichotomized by surgical technique based on whether glissonian pedicles were isolated and controlled (the individual group, n = 21) or controlled using endoscopic staples at once (the batch group, n = 14). RESULTS: Mean operation time was 265.3 +/- 21.3 minutes (mean +/- standard deviation) in the individual group and 170 +/- 22.9 minutes in the batch group. Operation time in the batch group was significantly shorter than the individual group (P = 0.007). Mean drainage length was 4.8 +/- 1.6 and 2.6 +/ 1.5 days in the individual and the batch group. There was significantly shorter in the batch group, also (P = 0.006). No transfusion was required in the batch group, but 4 patients in the individual group needed transfusion. Mean hospital stay was 10.7 +/- 1.1 and 9.4 +/- 0.8 days in the individual and the batch groups (P = 0.460). There were no significant complications or mortality in both groups. CONCLUSION: LLLS using endoscopic staples (batch group) was found to be an easier and safer technique without morbidity or mortality. PMID- 25114886 TI - A comparison between surgical resection and radiofrequency ablation in the treatment of hepatocellular carcinoma. AB - PURPOSE: The aim of this study was to compare the therapeutic effects of radiofrequency ablation (RFA) and hepatic resection (HR) with regards to procedural morbidity, mortality, overall survival (OS) and disease-free survival (DFS) rates in hepatocellular carcinoma (HCC) patients. METHODS: Retrospective studies were performed based on the medical records of 129 patients who underwent curative HR, and 57 who patients received RFA for HCC, between 2005 and 2009. The inclusion criteria of HCC were the presence of three or fewer nodules 3 cm or less in diameter or a single nodule of 5 cm or less. RESULTS: The 1-, 3- and 5 year OS rates in the HR group were 91.3%, 78.8%, and 64.9%, compared to 94.4%, 74.0%, and 74.0% in the RFA group, with no significant difference between the two groups (P = 0.725). The estimated 1- and 3-year DFS rates were 70.0% and 53.0% in the HR group and 65.2% and 24.7% in the RFA group, respectively. The DFS rates of HR group were significantly higher than RFA group (P = 0.015). Multivariate analysis identified that recurrence (P = 0.036) and portal hypertension (P = 0.036) were associated with OS and that portal hypertension (P = 0.048) and increased serum alpha-FP (P = 0.008) were the factors significantly associated with DFS. CONCLUSION: HCC within Milan criteria should consider hepatectomy as the primary treatment if the patient's liver function and general conditions are good enough to undergo surgical operation. But in that RFA revealed similar overall survival to HR, RFA can be an alternative therapy for patients who are eligible for surgical resection. PMID- 25114887 TI - Four-channel single incision laparoscopic cholecystectomy using a snake retractor: comparison between 3- and 4-channel SILC 4-channel single incision cholecystectomy. AB - PURPOSE: Single incision laparoscopic cholecystectomy (SILC) is a widely used method of performing cholecystectomy. A common technique used in SILC is a 3 channel method. However, exposure of Calot's triangle is limited in conventional 3-channel SILC. Therefore, we herein report the adequacy and feasibility of 4 channel SILC using a snake retractor. METHODS: Four hundred and fifteen SILC cases were performed between April 2010 and February 2013. We performed 326 SILC cases between April 2010 and September 2012 using the 3-channel method. We introduced a snake retractor for liver traction in October 2012, and 89 cases of 4-channel SILC using snake retractor have been performed since. RESULTS: Thirty patients (9.2%) in the 3-channel SILC group, and 23 patients (25.8%) in the 4 channel SILC group, were treated with percutaneous transhepatic gallbladder drainage insertion because of acute inflammation of the gallbladder (GB) before operation (P < 0.001). The mean operating time was 53.0 +/- 25.8 minutes in the 3 channel SILC group and 51.9 +/- 18.6 minutes in the 4-channel SILC group (P = 0.709). In the 3-channel SILC group, mean hospital stay was 3.0 +/- 3.3 days whereas it was 2.6 +/- 0.9 days in the 4-channel SILC group (P = 0.043). There were a total 9 cases (2.1%) of additional port usages, 6 cases (1.8%) in the 3 channel SILC group and 3 cases (3.4%) in the 4-channel SILC group (P = 0.411), due to cystic artery bleeding and bile leakage from gallbladder bed, but there were no open conversions. CONCLUSION: Benign diseases of the GB can be operated on using SILC with the 4-channel method using a snake retractor. PMID- 25114888 TI - Role of resection for Bismuth type IV hilar cholangiocarcinoma and analysis of determining factors for curative resection. AB - PURPOSE: Extended liver resection may provide long-term survival in selected patients with Bismuth type IV hilar cholangiocarcinoma (HCCA). The purpose of this study was to identify anatomical factors that predict curative-intended resection. METHODS: Thirty-three of 159 patients with Bismuth type IV HCCA underwent major hepato-biliary resection with curative intent (CIR) between 2000 and 2010. Disease extent and anatomical variations were analyzed as factors enabling CIR. RESULTS: CIR ratio with hilar trifurcation bile duct variation (13/16) was significantly higher than that with other bile duct variation types (18/25). Hilum to left second bile duct confluence and tumor infiltration over left second bile duct confluence lengths in right-sided CIR were significantly shorter than those lengths in left-sided CIR (10.8 +/- 4.9 and 2.7 +/- 0.8 mm vs. 16.5 +/- 8.4 and 7.0 +/- 5.3 mm, respectively). Left-sided CIR patients had a marginally higher proportion of tumors invading <=5 mm over the right second confluence than that in right-sided CIR patients (13/17 vs. 6/16; P = 0.061). The 3-year survival rate after CIR (28%) was significantly higher than after non-CIR (6.1%). CONCLUSION: We recommend the criteria of CIR as bile duct variation type, length of hilum to contralateral second bile duct confluence, and extent of tumor infiltration over the second confluence for Bismuth type IV HCCA. PMID- 25114889 TI - Pancreaticoduodenectomy for secondary periampullary cancer following extrahepatic bile duct cancer resection. AB - PURPOSE: This study addressed the feasibility and effect of surgical treatment of metachronous periampullary carcinoma after resection of the primary extrahepatic bile duct cancer. The performance of this secondary curative surgery is not well documented. METHODS: We reviewed, retrospectively, the medical records of 10 patients who underwent pancreaticoduodenectomy (PD) for secondary periampullary cancer following extrahepatic bileduct cancer resection from 1995 to 2011. RESULTS: The mean age of the 10 patients at the second operation was 61 years (range, 45-70 years). The primary cancers were 7 hilar cholangiocarcinomas, 2 middle common bile duct cancers, and one cystic duct cancer. The secondary cancers were 8 distal common bile duct cancers and 2 carcinomas of the ampulla of Vater. The second operations were 6 Whipple procedures and 4 pylorus-preserving pancreaticoduodenectomies. The mean interval between primary treatment and metachronous periampullary cancer was 20.6 months (range, 3.4-36.6 months). The distal resection margin after primary resection was positive for high grade dysplasia in one patient. Metachronous tumor was confirmed by periampullary pathology in all cases. Four of the 10 patients had delayed gastric emptying (n = 2) or pancreatic fistula (n = 2) after reoperation. There were no perioperative deaths. Median survival after PD was 44.6 months (range, 8.5-120.5 months). CONCLUSION: Based on the postoperative survival rate, PD may provide an acceptable protocol for resection in patients with metachronous periampullary cancer after resection of the extrahepatic bile duct cancer. PMID- 25114890 TI - Extremely rare case of extrahepatic duct phytobezoar treated with intraoperative transenteral endoscopy. AB - Phytobezoar is a rare cause of gastro-intestinal tract obstruction. Common sites of phytobezoar are the stomach and small bowel. Naturally, extrahepatic duct phytobezoar is near impossible due to anatomical structure and location such as ampulla of vater, common bile duct and bifurcation of bile duct. Here, we present an extremely rare case of extrahepatic duct phytobezoar that resulted in abdominal pain. We successfully treated the case with extraoperative transenteral endoscopic removal of phytobezoar. For its great rarity and particular treatment approach, we report this case with review of literature. PMID- 25114891 TI - Acute cholecystitis associated with Clonorchis sinensis infection. AB - Clonorchis sinensis is one of the most common causes of trematodiasis that is caused by the ingestion of raw fish contaminated with infective cysts. The adult flukes are predominantly present in the intrahepatic bile ducts, but occasionally they may be found in the pancreatic duct and extrahepatic bile ducts. The clinical manifestations depend on the number of flukes, the period of infestation, and complications such as pericholangitic abscess, cholangitis, bile duct stones, and cholangiocarcinoma. However, primary acute cholecystitis associated with C. sinensis infection is extremely rare. Herein, we report on a case of primary acute cholecystitis associated with C. sinensis infection. PMID- 25114892 TI - Salvage dual graft living donor liver transplantation after major hepatectomy. AB - Salvage living donor liver transplantation (LDLT) after major hepatectomy has been considered a challenging procedure due to operative complexity. We report a successful case of salvage dual graft LDLT after right hepatectomy. A 48-year-old male was transferred to Daegu Catholic University Medical Center because of duodenal variceal bleeding. He underwent right hepatectomy due to hepatocellular carcinoma four years prior. We performed LDLT with dual graft from his wife and sister. During operation, portal vein anastomosis of the right lobe graft was performed using an interposing cadaveric iliac vein graft and the right gastroepiploic artery was anastomosed to the hepatic artery of the left lobe graft. Adequate graft inflow was demonstrated by postoperative imaging studies. He has been doing well with normal graft function for 31 months. Salvage dual graft LDLT could be undertaken successfully in patients with prior major hepatectomy under accurate preoperative planning and proper surgical techniques. PMID- 25114894 TI - Trends in the incidence of human papillomavirus-related noncervical and cervical cancers in Alberta, Canada: a population-based study. AB - INTRODUCTION: Recent epidemiologic studies have suggested that the incidence of noncervical cancers associated with human papillomavirus (HPV) is increasing. We assessed temporal, age-specific and sex-specific changes in the incidence of HPV associated cancers in a population-based study. METHODS: We used the Alberta Cancer Registry, a registry of all cancers diagnosed in the province of Alberta, Canada, to identify patients with cancers of the oropharynx, cervix, vulva, vagina, anus and penis (cancers associated with HPV) between Jan. 1, 1975, and Dec. 31, 2009. We estimated the age-standardized incidence of each cancer by sex- and age-specific group and assessed the annual percentage change using joinpoint regression. RESULTS: The age-standardized incidence of oropharyngeal cancers increased for each 5-year interval of the study period among men (annual percentage change 3.4, p < 0.001) and women (annual percentage change 1.5, p = 0.009). For anal cancers, the age-standardized rates increased among women (annual percentage change 2.2, p < 0.001) and men (annual percentage change 1.8, p = 0.008). The age-standardized incidence of cervical cancer increased with age, reaching an annual percentage change of -3.5 among women aged 75-84 years (p = 0.04). The rates of other HPV-associated cancers (vulvar, vaginal and penile) showed little change. INTERPRETATION: Our findings showed increases in the incidence of the HPV-associated cancers of the oropharynx and anus among men and women, and increases in cervical cancer among younger women. The incidence of HPV related cancers in younger age groups should continue to be monitored. Programs to prevent HPV infection, such as vaccination, should be considered for males as well as females. PMID- 25114895 TI - Expression of pain among Mi'kmaq children in one Atlantic Canadian community: a qualitative study. AB - BACKGROUND: First Nation children have the highest rates of pain-related conditions among Canadian children, yet there is little research on how this population expresses its pain or how and whether the pain is successfully treated. The aim of this study was to understand how Mi'kmaq children express pain and how others interpret it. METHODS: We conducted a qualitative ethnographic study in a large Canadian Mi'kmaq community using interviews and conversation sessions. Participants included children and youth (n = 76), parents (n = 12) teachers (n = 7), elders (n = 6) and health care professionals (n = 13). RESULTS: Interpretive descriptive analysis was used and themes regarding pain expression, care seeking and pain management were identified. Pain expression included stoicism and hiding behaviour, and, when pain was discussed, it was via storytelling and descriptive language, such as similes. Participants reported feeling unheard, stereotyped and frustrated when they sought pain care. Frustration led to avoidance of seeking further care, perceptions of racism and repeat visits because of unsuccessful previous treatment. Participants voiced concerns about the utility of the numeric and faces pain scales to describe pain meaningfully. Positive encounters occurred when participants felt respected and heard. INTERPRETATION: Mi'kmaq children are stoic and often hide their pain. Community members feel frustrated and discriminated against when their pain is not identified, and conventional pain assessment tools may not be useful. If clinicians consider cultural context, build trust and allow for additional time to assess pain via storytelling or word descriptions as well as a family-centred approach, better pain care may occur. PMID- 25114897 TI - The construct validity and reliability of an assessment tool for competency in cochlear implant surgery. AB - INTRODUCTION: We introduce a rating tool that objectively evaluates the skills of surgical trainees performing cochlear implant surgery. METHODS: Seven residents and seven experts performed cochlear implant surgery sessions from mastoidectomy to cochleostomy on a standardized virtual reality temporal bone. A total of twenty-eight assessment videos were recorded and two consultant otolaryngologists evaluated the performance of each participant using these videos. RESULTS: Interrater reliability was calculated using the intraclass correlation coefficient for both the global and checklist components of the assessment instrument. The overall agreement was high. The construct validity of this instrument was strongly supported by the significantly higher scores in the expert group for both components. CONCLUSION: Our results indicate that the proposed assessment tool for cochlear implant surgery is reliable, accurate, and easy to use. This instrument can thus be used to provide objective feedback on overall and task-specific competency in cochlear implantation. PMID- 25114896 TI - Unique pattern of component gene disruption in the NRF2 inhibitor KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex in serous ovarian cancer. AB - The NFE2-related factor 2 (NRF2) pathway is critical to initiate responses to oxidative stress; however, constitutive activation occurs in different cancer types, including serous ovarian carcinomas (OVCA). The KEAP1/CUL3/RBX1 E3 ubiquitin ligase complex is a regulator of NRF2 levels. Hence, we investigated the DNA-level mechanisms affecting these genes in OVCA. DNA copy-number loss (CNL), promoter hypermethylation, mRNA expression, and sequence mutation for KEAP1, CUL3, and RBX1 were assessed in a cohort of 568 OVCA from The Cancer Genome Atlas. Almost 90% of cases exhibited loss-of-function alterations in any components of the NRF2 inhibitory complex. CNL is the most prominent mechanism of component disruption, with RBX1 being the most frequently disrupted component. These alterations were associated with reduced mRNA expression of complex components, and NRF2 target gene expression was positively enriched in 90% of samples harboring altered complex components. Disruption occurs through a unique DNA-level alteration pattern in OVCA. We conclude that a remarkably high frequency of DNA and mRNA alterations affects components of the KEAP1/CUL3/RBX1 complex, through a unique pattern of genetic mechanisms. Together, these results suggest a key role for the KEAP1/CUL3/RBX1 complex and NRF2 pathway deregulation in OVCA. PMID- 25114898 TI - Improvement of oxidative and metabolic parameters by cellfood administration in patients affected by neurodegenerative diseases on chelation treatment. AB - OBJECTIVE: This prospective pilot study aimed at evaluating the effects of therapy with antioxidant compounds (Cellfood, and other antioxidants) on patients affected by neurodegenerative diseases (ND), who displayed toxic metal burden and were subjected to chelation treatment with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA or EDTA). METHODS: Two groups of subjects were studied: (a) 39 patients affected by ND and (b) 11 subjects unaffected by ND (controls). The following blood parameters were analyzed before and after three months' treatment with chelation+Cellfood or chelation+other antioxidants: oxidative status (reactive oxygen species, ROS; total antioxidant capacity, TAC; oxidized LDL, oxLDL; glutathione), homocysteine, vitamin B12, and folate. RESULTS: After 3-months' chelation+Cellfood administration oxLDL decreased, ROS levels were significantly lower, and TAC and glutathione levels were significantly higher than after chelation+other antioxidants treatment, both in ND patients and in controls. Moreover, homocysteine metabolism had also improved in both groups. CONCLUSIONS: Chelation+Cellfood treatment was more efficient than chelation+other antioxidants improving oxidative status and homocysteine metabolism significantly in ND patients and controls. Although limited to a small number of cases, this study showed how helpful antioxidant treatment with Cellfood was in improving the subjects' metabolic conditions. PMID- 25114899 TI - Sensitization of cancer cells through reduction of total Akt and downregulation of salinomycin-induced pAkt, pGSk3beta, pTSC2, and p4EBP1 by cotreatment with MK 2206. AB - MK-2206 is an inhibitor of Akt activation. It has been investigated as an anticancer drug in clinical trials assessing the potential of pAkt targeting therapy. The purpose of this study was to identify conditions that increase the sensitivity of cancer cells to MK-2206. We found that the treatment of cancer cells with a high concentration of salinomycin (Sal) reduced total Akt protein levels but increased activated Akt levels. When cancer cells were cotreated with MK-2206 and Sal, both pAkt and total Akt levels were reduced. Using microscopic observation, an assessment of cleaved PARP, FACS analysis of pre-G1 region, and Hoechst staining, we found that Sal increased apoptosis of MK-2206-treated cancer cells. These results suggest that cotreatment with MK-2206 and Sal sensitizes cancer cells via reduction of both pAkt and total Akt. Furthermore, cotreatment of cancer cells with Sal and MK-2206 reduced pp70S6K, pmTOR, and pPDK1 levels. In addition, Sal-induced activation of GSK3beta, TSC2, and 4EBP1 was abolished by MK 2206 cotreatment. These results suggest that cotreatment using MK-2206 and Sal could be used as a therapeutic method to sensitize cancer cells through targeting of the PI3K/Akt/mTOR pathway. Our findings may contribute to the development of MK-2206-based sensitization therapies for cancer patients. PMID- 25114901 TI - Aromatherapy: does it help to relieve pain, depression, anxiety, and stress in community-dwelling older persons? AB - To examine the effectiveness of an aromatherapy programme for older persons with chronic pain. The community-dwelling elderly people who participated in this study underwent a four-week aromatherapy programme or were assigned to the control group, which did not receive any interventions. Their levels of pain, depression, anxiety, and stress were collected at the baseline and at the postintervention assessment after the conclusion of the four-week programme. Eighty-two participants took part in the study. Forty-four participants (37 females, 7 males) were in the intervention group and 38 participants (30 females, 8 males) were in the control group. The pain scores were 4.75 (SD 2.32) on a 10 point scale for the intervention group and 5.24 (SD 2.14) for the control group before the programme. There was a slight reduction in the pain score of the intervention group. No significant differences were found in the same-group and between-group comparisons for the baseline and postintervention assessments. The depression, anxiety, and stress scores for the intervention group before the programme were 11.18 (SD 6.18), 9.64 (SD 7.05), and 12.91 (SD 7.70), respectively. A significant reduction in negative emotions was found in the intervention group (P<0.05). The aromatherapy programme can be an effective tool to reduce pain, depression, anxiety, and stress levels among community-dwelling older adults. PMID- 25114900 TI - Novel resveratrol and 5-fluorouracil coencapsulated in PEGylated nanoliposomes improve chemotherapeutic efficacy of combination against head and neck squamous cell carcinoma. AB - Increasing consumption of tobacco and alcohol has led to a steady increase in the incidence of head and neck cancers in Asia. The drawbacks associated with the existing chemotherapeutic and surgical interventions have necessitated the development of a safer alternative for therapy of head and neck cancers. In this study we have explored the synergistic therapeutic potential of a phytochemical and chemotherapeutic agent using PEGylated liposomes as a delivery vehicle. Resveratrol and 5-fluorouracil were successfully coencapsulated in a single PEGylated nanoliposome. The thermal analysis and the nuclear magnetic resonance results revealed that resveratrol localized near the glycerol backbone of the liposomal membrane while 5-fluorouracil localized closer to the phosphate moiety, which influenced the release kinetics of both drugs. The nanoformulation was tested in vitro on a head and neck cancer cell line NT8e and was found to exhibit a GI50 similar to that of free 5-fluorouracil. Further, gene expression studies showed that the combination of resveratrol and 5-fluorouracil exhibited different effects on different genes that may influence the net antagonistic effect. The coencapsulation of resveratrol and 5-fluorouracil in a liposomal nanocarrier improved the cytotoxicity in comparison with the free drug combination when tested in vitro. PMID- 25114903 TI - miRSeq: a user-friendly standalone toolkit for sequencing quality evaluation and miRNA profiling. AB - MicroRNAs (miRNAs) present diverse regulatory functions in a wide range of biological activities. Studies on miRNA functions generally depend on determining miRNA expression profiles between libraries by using a next-generation sequencing (NGS) platform. Currently, several online web services are developed to provide small RNA NGS data analysis. However, the submission of large amounts of NGS data, conversion of data format, and limited availability of species bring problems. In this study, we developed miRSeq to provide alternatives. To test the performance, we had small RNA NGS data from four species, including human, rat, fly, and nematode, analyzed with miRSeq. The alignments results indicate that miRSeq can precisely evaluate the sequencing quality of samples regarding percentage of self-ligation read, read length distribution, and read category. miRSeq is a user-friendly standalone toolkit featuring a graphical user interface (GUI). After a simple installation, users can easily operate miRSeq on a PC or laptop by using a mouse. Within minutes, miRSeq yields useful miRNA data, including miRNA expression profiles, 3' end modification patterns, and isomiR forms. Moreover, miRSeq supports the analysis of up to 105 animal species, providing higher flexibility. PMID- 25114902 TI - Comparison of the Freiburg and Charlson comorbidity indices in predicting overall survival in elderly patients with newly diagnosed multiple myeloma. AB - Multiple myeloma occurs primarily in elderly patients. Considering the high prevalence of comorbidities, comorbidity is an important issue for the management of myeloma. However, the impact of comorbidity on clinical outcomes has not been fully investigated. We retrospectively analyzed patients with newly diagnosed myeloma. Comorbidities were assessed based on the Charlson comorbidity index (CCI) and the Freiburg comorbidity index (FCI). The CCI is a summary measure of 19 comorbid conditions. FCI is determined by performance status, renal impairment, and lung disease. This study included 127 patients with a median age of 71 years. Approximately half of the patients had additional disorders at the time of diagnosis, and diabetes mellitus was the most frequent diagnosis (18.9%). The most significant factors for prognosis among patient-related conditions were a history of solid cancer and performance status (ECOG>=2). The FCI score was divided into 3 groups (0, 1, and 2-3), and the CCI score was divided into 2 groups (2-3 and >=4). FCI was a strong prognostic tool for OS (P>0.001) and predicted clinical outcome better than CCI (P=0.059). In conclusion, FCI was more useful than CCI in predicting overall survival in elderly patients with myeloma. PMID- 25114904 TI - A simple model to assess the probability of invasion in ductal carcinoma in situ of the breast diagnosed by needle biopsy. AB - OBJECTIVES: The aim of the study was to develop a clinical prediction model for assessing the probability of having invasive cancer in the definitive surgical resection specimen in patients with biopsy diagnosis of ductal carcinoma in situ (DCIS) of the breast, to facilitate decision making regarding axillary surgery. METHODS: In 349 women with DCIS, predictors of invasion in the definitive resection specimen were identified. A model to predict the probability of invasion was developed and subsequently simplified to divide patients into two risk categories. The model's performance was validated on another patient population. RESULTS: Multivariate logistic regression revealed four independent predictors of invasion: (i) suspicious (micro)invasion in the biopsy specimen; (ii) visibility of the lesion on ultrasonography; (iii) size of the lesion on mammography>30 mm; (iv) clinical palpability of the lesion. The actual frequency of invasion in the high-risk patient group in the test and validation population was 52.6% and 48.3%, respectively; in the low-risk group it was 16.8% and 7.1%, respectively. CONCLUSION: The model proved to have good performance. In patients with a low probability of invasion, an axillary procedure can be omitted without a substantial risk of additional surgery. PMID- 25114905 TI - Therapeutic potential of tacrolimus on acute myocardial infarction in minipigs: analysis with serial cardiac magnetic resonance and changes at histological and protein levels. AB - This study investigates the therapeutic potential of intracoronary tacrolimus against acute myocardial infarction (AMI) in minipigs with serial cardiac magnetic resonance (CMR) and changes at histological and protein levels. Twelve minipigs subjected to permanent left anterior descending artery ligation were randomized as tac-treated group (n=6, with intracoronary tacrolimus treatment) and controls (n=6). CMR with cine and late gadolinium enhancement (LGE) studies were performed on postoperative days 2, 5, and 21. There were no significant differences in left ventricular function (LVF), contractility, and LGE between the two groups on day 2. On day 5, the tac-treated group showed a significantly higher ejection fraction, smaller infarct, and lower day-5/day-2 infarct ratio than controls. On day 21, the controls demonstrated further deterioration of LVF and infarct. Contrastingly, the tac-treated animals demonstrated preservation of LVF, contractility, significantly smaller infarct, and lower day-21/day-2 infarct ratios compared with those on day 5 and controls. The in vivo CMR results were correlated with in vitro findings on histology, immunostaining, and Western blotting which revealed significantly less fibrosis, higher vascularities, less CD68+ and CD40+ inflammatory cells, lower expressions of inflammatory (MMP-9, NF kappaB, and TNF-alpha), and apoptotic (Bax, Caspase-3, c-PARP) biomarkers, respectively, in tac-treated AMI minipigs than controls. PMID- 25114906 TI - Therapeutic efficacy of vitamin E delta-tocotrienol in collagen-induced rat model of arthritis. AB - Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease primarily involving inflammation of the joints. Although the management of the disease has advanced significantly in the past three decades, there is still no cure for RA. The aim of this study was to determine the therapeutic efficacy of delta tocotrienol, in the rat model of collagen-induced arthritis (CIA). Arthritis was induced by intradermal injection of collagen type II emulsified in complete Freund's adjuvant. CIA rats were orally treated with delta-tocotrienol (10 mg/kg) or glucosamine hydrochloride (300 mg/kg) from day 25 to 50. Efficacy was assessed based on the ability to reduce paw edema, histopathological changes, suppression of collagen-specific T-cells, and a reduction in C-reactive protein (CRP) levels. It was established that delta-tocotrienol had the most significant impact in lowering paw edema when compared to glucosamine treatment. Paw edema changes correlated well with histopathological analysis where there was a significant reversal of changes in groups treated with delta-tocotrienol. The results suggest that delta-tocotrienol is efficient in amelioration of collagen-induced arthritis. Vitamin E delta-tocotrienol may be of therapeutic value against rheumatoid arthritis. PMID- 25114907 TI - The effectiveness of functional electrical stimulation based on a normal gait pattern on subjects with early stroke: a randomized controlled trial. AB - OBJECTIVE: To investigate the effectiveness of four-channel FES based on a normal gait pattern on improving functional ability in subjects early after ischemic stroke. METHODS: Forty-five subjects were randomly assigned into a four-channel FES group (n=16), a placebo group (n=15), or a dual-channel group (n=14). Stimulation lasted for 30 min in each session with 1 session/day, 5 days a week for 3 weeks. All subjects were assessed at baseline, at 3 weeks of treatment, and at 3 months after the treatment had finished. The assessments included Fugl-Meyer Assessment (FMA), the Postural Assessment Scale for Stroke Patients (PASS), Berg Balance Scale (BBS), Functional Ambulation Category (FAC), and the Modified Barthel Index (MBI). RESULTS: All 3 groups demonstrated significant improvements in all outcome measurements from pre- to posttreatment and further gains at followup. The score of FMA and MBI improved significantly in the four-channel group at the end of the 3 weeks of training. And the scores of PASS, BBS, MBI, and FAC in the four-channel group were significantly higher than those of the placebo group. CONCLUSIONS: This study indicated that four-channel FES can improve motor function, balance, walking ability, and performance of activities of daily living in subjects with early ischemic stroke. PMID- 25114908 TI - The protective effect of Agaricus blazei Murrill, submerged culture using the optimized medium composition, on alcohol-induced liver injury. AB - Agaricus blazei Murrill (ABM), an edible mushroom native to Brazil, is widely used for nonprescript and medicinal purposes. Alcohol liver disease (ALD) is considered as a leading cause for a liver injury in modern dietary life, which can be developed by a prolonged or large intake of alcohol. In this study, the medium composition of ABM was optimized using response surface methodology for maximum mycelial biomass and extracellular polysaccharide (EPS) production. The model predicts to gain a maximal mycelial biomass and extracellular polysaccharide at 1.047 g/100 mL, and 0.367 g/100 mL, respectively, when the potato is 29.88 g/100 mL, the glucose is 1.01 g/100 mL, and the bran is 1.02 g/100 mL. The verified experiments showed that the model was significantly consistent with the model prediction and that the trends of mycelial biomass and extracellular polysaccharide were predicted by artificial neural network. After that, the optimized medium was used for the submerged culture of ABM. Then, alcohol-induced liver injury in mice model was used to examine the protective effect of ABM cultured using the optimized medium on the liver. And the hepatic histopathological observations showed that ABM had a relatively significant role in mice model, which had alcoholic liver damage. PMID- 25114910 TI - Phylogenetic and in silico functional analyses of thermostable-direct hemolysin and tdh-related encoding genes in Vibrio parahaemolyticus and other Gram-negative bacteria. AB - Emergence and spread of pandemic strains of Vibrio parahaemolyticus have drawn attention to make detailed study on their genomes. The pathogenicity of V. parahaemolyticus has been associated with thermostable-direct hemolysin (TDH) and/or TDH-related hemolysin (TRH). The present study evaluated characteristics of tdh and trh genes, considering the phylogenetic and in silico functional features of V. parahaemolyticus and other bacteria. Fifty-two tdh and trh genes submitted to the GenBank were analyzed for sequence similarity. The promoter sequences of these genes were also analyzed from transcription start point to -35 regions and correlated with amino acid substitution within the coding regions. The phylogenetic analysis revealed that tdh and trh are highly distinct and also differ within the V. parahaemolyticus strains that were isolated from different geographical regions. Promoter sequence analysis revealed nucleotide substitutions and deletions at -18 and -19 positions among the pandemic, prepandemic, and nonpandemic tdh sequences. Many amino acid substitutions were also found within the signal peptide and also in the matured protein region of several TDH proteins as compared to TDH-S protein of pandemic V. parahaemolyticus. Experimental evidences are needed to recognize the importance of substitutions and deletions in the tdh and trh genes. PMID- 25114909 TI - Heavy silicone oil and intraocular inflammation. AB - In the past two decades, many advances have been made in vitrectomy instrumentation, surgical techniques, and the use of different tamponade agents. These agents serve close retinal breaks, confine eventual retinal redetachment, and prevent proliferative vitreoretinopathy (PVR). Long-acting gases and silicone oil are effective internal tamponade agents; however, because their specific gravity is lower than that of the vitreous fluid, they may provide adequate support for the superior retina but lack efficacy for the inferior retina, especially when the fill is subtotal. Thus, a specific role may exist for an internal tamponade agent with a higher specific gravity, such as heavy silicone oils (HSOs), Densiron 68, Oxane HD, HWS 45-300, HWS 46-3000, and HeavySil. Some clinical evidence seems to presume that heavy tamponades are more prone to intraocular inflammation than standard silicone if they remain in the eye for several months. In this review, we discuss the fundamental clinical and biochemical/molecular mechanisms involved in the inflammatory response after the use of heavy tamponade: toxicity due to impurities or instability of the agent, direct toxicity and immunogenicity, oil emulsification, and mechanical injury due to gravity. The physical and chemical properties of various HSOs and their efficacy and safety profiles are also described. PMID- 25114911 TI - Epigenetic silencing of CXCR4 promotes loss of cell adhesion in cervical cancer. AB - In the network of chemokine signaling pathways, recent reports have described the SDF-1alpha/CXCR4 axis and its role in cancer progression and metastasis. Interestingly, we found downregulation of CXCR4 at both transcript and protein level in cervical cancer cell lines and primary tumors. We also found CXCR4 promoter hypermethylation in cervical cancer cell lines and primary biopsy samples. DNA hypomethylating drug 5-AZA-2'-deoxycytidine and histone deacetylase inhibitor Trichostatin A treatments in cell lines reactivate both CXCR4 transcription and protein expression. Cell adhesion assay demonstrated that autocrine SDF-1alpha promotes the loss of cell adhesion while paracrine SDF 1alpha predominantly protects the normal cervical cells from loss of cell adhesion. Cervical cancer cell line C-33A having increased expression of CXCR4 after TSA treatment showed increased cell adhesion by paracrine source of SDF 1alpha in comparison to untreated C-33A. These findings demonstrate the first evidence that epigenetic silencing of CXCR4 makes the cells inefficient to respond to the paracrine source of SDF-1alpha leading to loss of cell adhesion, one of the key events in metastases and progression of the disease. Our results provide novel insight of SDF-1alpha/CXCR4 signaling in tumor microenvironment which may be promising to further delineate molecular mechanism of cervical carcinogenesis. PMID- 25114912 TI - Modulation of circulating macrophage migration inhibitory factor in the elderly. AB - Aging increases the risk for cardiovascular morbidity and mortality. Chronic low grade inflammation deteriorates vascular function, increases age-related vascular stiffness, and affects hemodynamics. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) is a major mediator of atherosclerosis. Plasma MIF levels are associated with arterial stiffness, a hallmark of vascular aging. Preclinical studies show that blockade of MIF leads to atherosclerotic plaque regression. Nutritional approaches provide opportunities to counteract age related inflammation. Following a chronic dietary supplementation with the micronutrient nitrate has been demonstrated to improve vascular stiffness. Whether dietary nitrate affects circulating MIF levels is not known. In a randomized placebo-controlled, double-blinded study, elderly subjects received a dietary nitrate supplementation for 4 weeks. Dietary nitrate led to a decrease in plasma MIF levels in the elderly and to an improvement in vascular functions. This was associated with a reduction in central systolic blood pressure. Our data show that supplementation with dietary nitrate is associated with a reduction of circulating MIF levels along with an improvement in vascular function. This supports the concept of dietary approaches to modulate age-related changes of vascular functions. PMID- 25114915 TI - Molecular image-guided theranostic and personalized medicine 2013. PMID- 25114913 TI - Profiling of biomarkers for the exposure of polycyclic aromatic hydrocarbons: lamin-A/C isoform 3, poly[ADP-ribose] polymerase 1, and mitochondria copy number are identified as universal biomarkers. AB - This study investigated the profiling of polycyclic aromatic hydrocarbon- (PAH-) induced genotoxicity in cell lines and zebrafish. Each type of cells displayed different proportionality of apoptosis. Mitochondrial DNA (mtDNA) copy number was dramatically elevated after 5-day treatment of fluoranthene and pyrene. The notable deregulated proteins for PAHs exposure were displayed as follows: lamin A/C isoform 3 and annexin A1 for benzopyrene; lamin-A/C isoform 3 and DNA topoisomerase 2-alpha for pentacene; poly[ADP-ribose] polymerase 1 (PARP-1) for fluoranthene; and talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them, lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein expression study. Obvious morphological abnormalities including curved backbone and cardiomegaly in zebrafish were observed in the 54 hpf with more than 400 nM of benzopyrene. In conclusion, the change of mitochondrial genome (increased mtDNA copy number) was closely associated with PAH exposure in cell lines and mesenchymal stem cells. Lamin-A/C isoform 3, talin-1, and annexin A1 were identified as universal biomarkers for PAHs exposure. Zebrafish, specifically at embryo stage, showed suitable in vivo model for monitoring PAHs exposure to hematopoietic tissue and other organs. PMID- 25114916 TI - Physiological and behavioral stress and anxiety in children with autism spectrum disorders during routine oral care. AB - BACKGROUND: Children with autism spectrum disorders (ASD) commonly exhibit uncooperative behaviors which impede oral care. Previous studies have utilized dentist-report measures of uncooperative behaviors in children with ASD but none have utilized an objective measure of children's behavior or a physiological measure of distress. This study investigated behavioral and physiological distress in children with ASD during routine oral care and examined factors associated with this distress. METHODS: Participants were 44 children (n=22 typical, n=22 ASD) aged 6-12 receiving routine dental cleanings. Behavioral and physiological measures of stress and anxiety were collected during dental cleanings. RESULTS: Children with ASD exhibited greater distress, compared to the typical group, on dentist-report and researcher-coded measures of overt distress behaviors and on physiological measures. Correlations between physiological and behavioral measures of distress were found in the ASD but not in the typical group. Behavioral distress was correlated with age in the typical group and with expressive communication ability and sensory processing difficulties in the ASD group; physiological distress was correlated with parent-report of anxiety in the typical group and sensory processing difficulties in the ASD group. CONCLUSIONS: Novel strategies may be required to decrease behavioral and physiological distress in children with ASD in the dental clinic. PMID- 25114914 TI - Antidiabetic effect of Sida cordata in alloxan induced diabetic rats. AB - Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties. PMID- 25114918 TI - Comparative study of corneal endothelial cell damage after femtosecond laser assisted deep stromal dissection. AB - PURPOSE: To find a relatively safe designed stromal bed thickness to avoid endothelial damage for lamellar keratoplasty with an Allegretto Wavelight FS200 femtosecond laser. METHODS: Twelve rabbits were randomly divided into 50 MUm and 150 MUm groups according to the anticipated residue stromal bed thickness preparation with a femtosecond laser. Six rabbits without laser cutting were used as a control group. Central endothelial images were analyzed with in vivo confocal microscopy and scanning electron microscopy. The apoptosis of endothelium was evaluated with Hoechst 33342 staining and a TUNEL assay. RESULTS: The endothelium of the 50 MUm group had extensive injuries upon in vivo confocal and scanning electron microscopic observation, and minor injuries were observed in the 150 MUm group. Moreover, more apoptotic cells were observed in the 50 MUm group. CONCLUSIONS: When using a FS200 femtosecond laser assisted anterior lamellar keratoplasty, there was minor endothelium damage with a 150 MUm stromal bed, and a more than 150 MUm thickness stromal bed design may prevent the damage of corneal endothelium. PMID- 25114919 TI - Advances in miniaturized instruments for genomics. AB - In recent years, a lot of demonstrations of the miniaturized instruments were reported for genomic applications. They provided the advantages of miniaturization, automation, sensitivity, and specificity for the development of point-of-care diagnostics. The aim of this paper is to report on recent developments on miniaturized instruments for genomic applications. Based on the mature development of microfabrication, microfluidic systems have been demonstrated for various genomic detections. Since one of the objectives of miniaturized instruments is for the development of point-of-care device, impedimetric detection is found to be a promising technique for this purpose. An in-depth discussion of the impedimetric circuits and systems will be included to provide total consideration of the miniaturized instruments and their potential application towards real-time portable imaging in the "-omics" era. The current excellent demonstrations suggest a solid foundation for the development of practical and widespread point-of-care genomic diagnostic devices. PMID- 25114917 TI - Gambling disorder during dopamine replacement treatment in Parkinson's disease: a comprehensive review. AB - Gambling Disorder (GD) is characterized by "the failure to resist gambling impulses despite severe personal, family or occupational consequences". In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM V), GD replaces the DSM-IV diagnosis of Pathological Gambling (PG). GD estimated prevalence ranges between 0.4% and 3.4% within the adult population and it seems to be more common in patients with Parkinson's disease (PD). In this population, GD recently has become more widely recognized as a possible complication of dopamine agonist (DA) therapy. This association has aroused great interest for the dramatic impact GD has on patients' quality of life. Management of PG in patients with PD could be demanding. It is based on patient and caregiver education, modification of dopamine replacement therapy, and in some cases psychoactive drug administration. In this review article, the authors provide an overview of GD pathogenesis during DA therapy as well as a summary of available treatment options. PMID- 25114920 TI - Exopolysaccharide from Ganoderma applanatum as a promising bioactive compound with cytostatic and antibacterial properties. AB - A new exopolysaccharide preparation isolated from stationary cultures of the white rot fungus Ganoderma applanatum (GpEPS) was tested in terms of its bioactive properties including its cytotoxic and immunostimulatory effect. The results indicate that the tested GpEPS (at concentrations above 22.85 ug/mL and 228.5 ug/mL) may exhibit selective activity against tumor cells (cell lines SiHa) and stimulate production of TNF-alpha THP-1-derived macrophages at the level of 752.17 pg/mL. The GpEPS showed antibacterial properties against Staphyloccoccus aureus and a toxic effect against Vibrio fischeri cells (82.8% cell damage). High cholesterol-binding capacity and triglycerides-binding capacity (57.9% and 41.6% after 24 h of incubation with the tested substances, resp.) were also detected for the investigated samples of GpEPS. PMID- 25114922 TI - Modelling the aggregation process of cellular slime mold by the chemical attraction. AB - We put into exercise a comparatively innovative analytical modus operandi, the homotopy decomposition method (HDM), for solving a system of nonlinear partial differential equations arising in an attractor one-dimensional Keller-Segel dynamics system. Numerical solutions are given and some properties show evidence of biologically practical reliance on the parameter values. The reliability of HDM and the reduction in computations give HDM a wider applicability. PMID- 25114921 TI - Development of new method for simultaneous analysis of piracetam and levetiracetam in pharmaceuticals and biological fluids: application in stability studies. AB - RP-HPLC ultraviolet detection simultaneous quantification of piracetam and levetiracetam has been developed and validated. The chromatography was obtained on a Nucleosil C18 column of 25 cm*0.46 cm, 10 MUm, dimension. The mobile phase was a (70:30 v/v) mixture of 0.1 g/L of triethylamine and acetonitrile. Smooth flow of mobile phase at 1 mL/min was set and 205 nm wavelength was selected. Results were evaluated through statistical parameters which qualify the method reproducibility and selectivity for the quantification of piracetam, levetiracetam, and their impurities hence proving stability-indicating properties. The proposed method is significantly important, permitting the separation of the main constituent piracetam from levetiracetam. Linear behavior was observed between 20 ng/mL and 10,000 ng/mL for both drugs. The proposed method was checked in bulk drugs, dosage formulations, physiological condition, and clinical investigations and excellent outcome was witnessed. PMID- 25114923 TI - Biomechanics of interspinous devices. AB - A number of interspinous devices (ISD) have been introduced in the lumbar spine implant market. Unfortunately, the use of these devices often is not associated with real comprehension of their biomechanical role. The aim of this paper is to review the biomechanical studies about interspinous devices available in the literature to allow the reader a better comprehension of the effects of these devices on the treated segment and on the adjacent segments of the spine. For this reason, our analysis will be limited to the interspinous devices that have biomechanical studies published in the literature. PMID- 25114924 TI - The trend in distribution of Q223R mutation of leptin receptor gene in amoebic liver abscess patients from North India: a prospective study. AB - Host genetic susceptibility is an important risk factor in infectious diseases. We explored the distribution of Q223R mutation in leptin receptor gene of amoebic liver abscess (ALA) patients of North India. A total of 55 ALA samples along with 102 controls were subjected to PCR-RFLP analysis. The frequency of allele "G" (coding for arginine) was in general high in Indian population irrespective of the disease. Our results of Fisher exact test shows that heterozygous mutant (QQ versus QR, P=0.049) and homozygous mutant (QQ versus RR, P=0.004) were significantly associated with amoebic liver abscess when compared with homozygous wild (QQ). PMID- 25114925 TI - Automated tissue classification framework for reproducible chronic wound assessment. AB - The aim of this paper was to develop a computer assisted tissue classification (granulation, necrotic, and slough) scheme for chronic wound (CW) evaluation using medical image processing and statistical machine learning techniques. The red-green-blue (RGB) wound images grabbed by normal digital camera were first transformed into HSI (hue, saturation, and intensity) color space and subsequently the "S" component of HSI color channels was selected as it provided higher contrast. Wound areas from 6 different types of CW were segmented from whole images using fuzzy divergence based thresholding by minimizing edge ambiguity. A set of color and textural features describing granulation, necrotic, and slough tissues in the segmented wound area were extracted using various mathematical techniques. Finally, statistical learning algorithms, namely, Bayesian classification and support vector machine (SVM), were trained and tested for wound tissue classification in different CW images. The performance of the wound area segmentation protocol was further validated by ground truth images labeled by clinical experts. It was observed that SVM with 3rd order polynomial kernel provided the highest accuracies, that is, 86.94%, 90.47%, and 75.53%, for classifying granulation, slough, and necrotic tissues, respectively. The proposed automated tissue classification technique achieved the highest overall accuracy, that is, 87.61%, with highest kappa statistic value (0.793). PMID- 25114926 TI - GABAB receptors expressed in human aortic endothelial cells mediate intracellular calcium concentration regulation and endothelial nitric oxide synthase translocation. AB - GABAB receptors regulate the intracellular Ca2+ concentration ([Ca2+]i) in a number of cells (e.g., retina, airway epithelium and smooth muscle), but whether they are expressed in vascular endothelial cells and similarly regulate the [Ca2+]i is not known. The purpose of this study was to investigate the expression of GABAB receptors, a subclass of receptors to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), in cultured human aortic endothelial cells (HAECs), and to explore if altering receptor activation modified [Ca2+]i and endothelial nitric oxide synthase (eNOS) translocation. Real-time PCR, western blots and immunofluorescence were used to determine the expression of GABAB1 and GABAB2 in cultured HAECs. The effects of GABAB receptors on [Ca2+]i in cultured HAECs were demonstrated using fluo-3. The influence of GABAB receptors on eNOS translocation was assessed by immunocytochemistry. Both GABAB1 and GABAB2 mRNA and protein were expressed in cultured HAECs, and the GABAB1 and GABAB2 proteins were colocated in the cell membrane and cytoplasm. One hundred MUM baclofen caused a transient increase of [Ca2+]i and eNOS translocation in cultured HAECs, and the effects were attenuated by pretreatment with the selective GABAB receptor antagonists CGP46381 and CGP55845. GABAB receptors are expressed in HAECs and regulate the [Ca2+]i and eNOS translocation. Cultures of HAECs may be a useful in vitro model for the study of GABAB receptors and vascular biology. PMID- 25114927 TI - Butylidenephthalide blocks potassium channels and enhances basal tension in isolated guinea-pig trachea. AB - Butylidenephthalide (Bdph, 30~300 MUM), a constituent of Ligusticum chuanxiong Hort., significantly enhanced tension in isolated guinea-pig trachea. In this study, we investigate the mechanism(s) of Bdph-induced contraction in the tissue. Isolated trachea was bathed in 5 mL of Krebs solution containing indomethacin (3 MUM), and its tension changes were isometrically recorded. Cromakalim (3 MUM), an ATP-dependent K+ channel opener, significantly antagonized the Bdph-induced enhancement of baseline tension. Bdph (300 MUM) also significantly antagonized cromakalim-induced relaxation. Bdph (300 MUM) did not significantly influence the antagonistic effects of glibenclamide (GBC, 1 MUM) and tetraethylammonium (TEA, 8 mM) against the cromakalim-induced relaxation. However, Bdph (300 MUM) and 4 aminopiridine (4-AP, 5 mM), a blocker of K v 1 family of K+ channels, in combination significantly rightward shifted the log concentration-relaxation curve of cromakalim. The antagonistic effect of the combination almost equals the sum of the individual effects of Bdph and 4-AP, suggesting that the antagonistic mechanism of Bdph may be similar to that of 4-AP. All calcium channel blockers influenced neither the baseline tension nor antagonistic effect of Bdph against cromakalim. In conclusion, Bdph may be similar to 4-AP, a blocker of K v 1 family of K+ channels, to enhance the baseline tension of guinea-pig trachea. PMID- 25114928 TI - Geodermatophilus poikilotrophi sp. nov.: a multitolerant actinomycete isolated from dolomitic marble. AB - A novel Gram-reaction-positive, aerobic actinobacterium, tolerant to mitomycin C, heavy metals, metalloids, hydrogen peroxide, desiccation, and ionizing- and UV radiation, designated G18T, was isolated from dolomitic marble collected from outcrops in Samara (Namibia). The growth range was 15-35 degrees C, at pH 5.5-9.5 and in presence of 1% NaCl, forming greenish-black coloured colonies on GYM Streptomyces agar. Chemotaxonomic and molecular characteristics of the isolate matched those described for other representatives of the genus Geodermatophilus. The peptidoglycan contained meso-diaminopimelic acid as diagnostic diaminoacid. The main phospholipids were phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, and small amount of diphosphatidylglycerol. MK-9(H4) was the dominant menaquinone and galactose was detected as diagnostic sugar. The major cellular fatty acids were branched-chain saturated acids iso-C16:0 and iso C15:0 and the unsaturated C17:1 omega8c and C16:1 omega7c. The 16S rRNA gene showed 97.4-99.1% sequence identity with the other representatives of genus Geodermatophilus. Based on phenotypic results and 16S rRNA gene sequence analysis, strain G18T is proposed to represent a novel species, Geodermatophilus poikilotrophi. Type strain is G18T (=DSM 44209T=CCUG 63018T). The INSDC accession number is HF970583. The novel R software package lethal was used to compute the lethal doses with confidence intervals resulting from tolerance experiments. PMID- 25114929 TI - Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus. AB - Diabetic encephalopathy is one of the severe complications in patients with diabetes mellitus. Findings indicate that saffron extract has antioxidant properties but its underlying beneficial effects on diabetic encephalopathy were unclear. In the present study, the protective activities of saffron were evaluated in diabetic encephalopathy. Saffron at 40 and 80 mg/kg significantly increased body weight and serum TNF-alpha and decreased blood glucose levels, glycosylated serum proteins, and serum advanced glycation endproducts (AGEs) levels. Furthermore, significant increase in HDL and decrease (P<0.05) in cholesterol, triglyceride, and LDL were observed after 28 days of treatment. At the end of experiments, the hippocampus tissue was used for determination of glutathione content (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. Furthermore, saffron significantly increased GSH, SOD, and CAT but remarkably decreased cognitive deficit, serum TNF-alpha, and induced nitric oxide synthase (iNOS) activity in hippocampus tissue. Our findings indicated that saffron extract may reduce hyperglycemia and hyperlipidemia risk and also reduce the oxidative stress in diabetic encephalopathy rats. This study suggested that saffron extract might be a promising candidate for the improvement of chemically induced diabetes and its complications. PMID- 25114930 TI - Acetylated hyaluronic acid: enhanced bioavailability and biological studies. AB - Hyaluronic acid (HA), a macropolysaccharidic component of the extracellular matrix, is common to most species and it is found in many sites of the human body, including skin and soft tissue. Not only does HA play a variety of roles in physiologic and in pathologic events, but it also has been extensively employed in cosmetic and skin-care products as drug delivery agent or for several biomedical applications. The most important limitations of HA are due to its short half-life and quick degradation in vivo and its consequently poor bioavailability. In the aim to overcome these difficulties, HA is generally subjected to several chemical changes. In this paper we obtained an acetylated form of HA with increased bioavailability with respect to the HA free form. Furthermore, an improved radical scavenging and anti-inflammatory activity has been evidenced, respectively, on ABTS radical cation and murine monocyte/macrophage cell lines (J774.A1). PMID- 25114931 TI - Integrated analysis identifies interaction patterns between small molecules and pathways. AB - Previous studies have indicated that the downstream proteins in a key pathway can be potential drug targets and that the pathway can play an important role in the action of drugs. So pathways could be considered as targets of small molecules. A link map between small molecules and pathways was constructed using gene expression profile, pathways, and gene expression of cancer cell line intervened by small molecules and then we analysed the topological characteristics of the link map. Three link patterns were identified based on different drug discovery implications for breast, liver, and lung cancer. Furthermore, molecules that significantly targeted the same pathways tended to treat the same diseases. These results can provide a valuable reference for identifying drug candidates and targets in molecularly targeted therapy. PMID- 25114933 TI - Solid-nanoemulsion preconcentrate for oral delivery of paclitaxel: formulation design, biodistribution, and gamma scintigraphy imaging. AB - Aim of present study was to develop a solid nanoemulsion preconcentrate of paclitaxel (PAC) using oil [propylene glycol monocaprylate/glycerol monooleate, 4:1 w/w], surfactant [polyoxyethylene 20 sorbitan monooleate/polyoxyl 15 hydroxystearate, 1:1 w/w], and cosurfactant [diethylene glycol monoethyl ether/polyethylene glycol 300, 1:1 w/w] to form stable nanocarrier. The prepared formulation was characterized for droplet size, polydispersity index, and zeta potential. Transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to assess surface morphology and drug encapsulation and its integrity. Cumulative drug release of prepared formulation through dialysis bag and permeability coefficient through everted gut sac were found to be remarkably higher than the pure drug suspension and commercial intravenous product (Intaxel), respectively. Solid nanoemulsion preconcentrate of PAC exhibited strong inhibitory effect on proliferation of MCF-7 cells in MTT assay. In vivo systemic exposure of prepared formulation through oral administration was comparable to that of Intaxel in gamma scintigraphy imaging. Our findings suggest that the prepared solid nanoemulsion preconcentrate can be used as an effective oral solid dosage form to improve dissolution and bioavailability of PAC. PMID- 25114935 TI - Evaluation of medicine prescription pattern using World Health Organization prescribing indicators in Iran: A cross-sectional study. AB - OBJECTIVE: The objective was to quantify the specialists' prescription pattern in Iran and to point out the prescribing behavioral differences among several specialties. METHODS: A retrospective cross-sectional study was carried out on the claim data. National prescription data were obtained on the basis of the claims that the pharmacies submitted to the insurers during 1 year period of the study. More than 85 million prescriptions were analyzed using "Rx-Analyst" software that is designed and applied by National Committee of Rational Use of Medicines in Iran. Specified medical specialties were considered and the World Health Organization prescription indicators were used to evaluate the physicians' prescribing behavior. FINDINGS: Average items per prescription were ranged from 3.68 in cardiologists' to 2.06 in dermatologists' prescriptions. The highest and the lowest mean price were belonged to neurologists' and ophthalmologists' prescriptions, respectively. In addition, 45% of patients received antibiotics, 41% of patients received injectable form of drugs, and 23% received corticosteroids. A high tendency toward prescribing corticosteroids and antibiotics as well as an injectable form of medicines was observed among general physicians. CONCLUSION: There is an inevitable need to improve prescription habits among different specialties, especially among general practitioners. This causes the policymakers to put more emphasis on priorities such as continuous education. PMID- 25114934 TI - Simultaneous detection and differentiation of highly virulent and classical Chinese-type isolation of PRRSV by real-time RT-PCR. AB - Porcine reproductive and respiratory syndrome (PRRS) is a leading disease in pig industry worldwide and can result in serious economic losses each year. The PRRS epidemic situation in China has been very complicated since the unprecedented large-scale highly pathogenic PRRS (HP-PRRS) outbreaks in 2006. And now the HP PRRS virus (HP-PRRSV) and classical North American type PRRSV strains have coexisted in China. Rapid differential detection of the two strains of PRRSV is very important for effective PRRS control. The real-time RT-PCR for simultaneous detection and differentiation of HP-PRRSV and PRRSV by using both SYBR Green and TaqMan probes was developed and validated. Both assays can be used for rapid detection and strain-specific identification of HP-PRRSV and PRRSV. However, the TaqMan probe method had the highest detection rate whereas the conventional RT PCR was the lowest. The real-time RT-PCR developed based on SYBR Green and TaqMan probe could be used for simultaneous detection and differentiation of HP-PRRSV and PRRSV in China, which will benefit much the PRRS control and research. PMID- 25114936 TI - Identification and management of adverse effects of antipsychotics in a tertiary care teaching hospital. AB - OBJECTIVE: Antipsychotics have revolutionized psychiatry by allowing significant numbers of patients in long-term hospital settings to be discharged and successfully maintained in the community. However, these medications are also associated with a range of adverse events ranging from mostly annoying to rarely dangerous. This study is carried out to identify the adverse drug reactions (ADRs) to antipsychotics and its management in psychiatric patients. METHODS: Prospective interventional study was conducted in the psychiatric unit of a tertiary care hospital. Patients of any age and either sex prescribed with at least one antipsychotic were included and monitored for ADRs. FINDINGS: Among the 517 patients receiving antipsychotics, a total of 289 ADRs were identified from 217 patients at an overall incidence rate of 41.97%. Sixty-seven different kinds of ADRs were observed in the study patients. Central and peripheral nervous system was the most commonly affected system organ class (n = 59) and weight gain (n = 30) was the most commonly observed ADR. Olanzapine was most commonly implicated in reported ADRs (n = 92) followed by risperidone (n = 59). Of the 289 ADRs, 80% required interventions including cessation of drug and/or specific/symptomatic/nonpharmacological treatment. CONCLUSION: This post marketing surveillance study provides a representative data of the ADR profile of the antipsychotics likely to be encountered in psychiatric patients in an Indian tertiary care hospital. PMID- 25114932 TI - Clinical study of nasopharyngeal carcinoma treated by helical tomotherapy in China: 5-year outcomes. AB - BACKGROUND: To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT). METHODS: Between September 2007 and August 2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients were treated with radiation therapy as single modality, 129 with additional cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy. RESULTS: Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and greater toxicities were rarely noted. The median followup was 32 (3-38) months. The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%, 98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression analysis showed that age and T stage were independent predictors for 3-year OS. CONCLUSIONS: Helical tomotherapy for NPC patients achieved excellent 3-year locoregional control, distant metastasis-free survival, and overall survival, with relatively minor acute and late toxicities. Age and T stage were the main prognosis factors. PMID- 25114937 TI - Education alone is not enough in ventilator associated pneumonia care bundle compliance. AB - OBJECTIVE: Ventilator-associated pneumonia (VAP) described as a secondary and preventable consequence in mechanically ventilated patients, emerges 48 h or more after patients intubation. Considering the high morbidity and mortality rate of VAP and the fact that VAP is preventable, it seemed necessary to evaluate care bundle compliance rate and effect of education on its improvement. METHODS: This observational study was conducted on 10 Intensive Care Units (ICUs) of four university affiliated hospitals in three steps. In the first step, VAP care bundle compliance including head of bed (HOB) elevation, endotracheal cuff pressure (ETCP), mouthwash time, utilizing close suction systems, subglottic secretion drainage, type of suction package, and hand wash before suctioning was evaluated. In the second and third steps, ICU staffs were trained and its effect on VAP care bundle compliance was investigated. Finally, an inquiry from nurses was conducted to evaluate the obtained results. FINDINGS: A total of 552 checklists consisting of 294 observations in the pre-education group and 258 observations in the posteducation group were filled. Mean VAP care bundle compliance in pre-education and posteducation stages was 36.5% and 41.2%, respectively (P > 0.05). Except for patients' mouth washing, there were no improvement in HOB elevation (>30 degrees ), hand washing and ETCP after education. Based on the results of questionnaire received from nurses at the end of study, more than 90% of nurses believed that lack of rigid monitoring of VAP care bundle is a main reason of low adherence for VAP care bundle compliance. CONCLUSION: The adherence to VAP care bundle was inappropriate. Education seems to be ineffective on improving VAP care bundle compliance. Frequent recall of the necessity of the VAP care bundle and the continuous supervision of ICU staffs is highly recommended. PMID- 25114938 TI - Assessing health conditions and medication use among the homeless community in Long Beach, California. AB - OBJECTIVE: Persons experiencing homelessness are a vulnerable population and are at increased risk for morbidity and all-cause mortality compared to the general population. This study sought to evaluate medication use, regular physician visits, and identify health conditions among the homeless population of Long Beach, California. METHODS: Two "brown bag" medication review events were held at homeless shelters in the Long Beach area. Demographic information, medication use, and comorbid disease states were obtained through surveys. FINDINGS: Three fourths of the cohort (95 participants) consisted of males, and the average age of participants was 48 years. Psychiatric disorders and cardiovascular disease were the most common disease states reported at 32% and 46%, respectively and so were medications used in treating these chronic diseases. Medication adherence was found to be a significant problem in this population, where more than 30% of patients were nonadherent to medications for chronic diseases. Furthermore, foot problems, hearing and vision difficulties constitute the most commonly overlooked health problems within the homeless population. CONCLUSION: Based on this and other similar finding, we must accept that the homeless represent a vulnerable population, and that because of this fact, more programs should be focused at improving availability and access to health care among the homeless. Regarding the high number of reported health problems in the study, more studies are needed and more studies should incorporate screening for foot, hearing, and vision issues, both to increase awareness and to provide an opportunity for devising possible solutions to these highly preventable conditions. PMID- 25114939 TI - Adherence to American society of health-system pharmacists surgical antibiotic prophylaxis guidelines in a teaching hospital. AB - OBJECTIVE: Surgical site infections are the second most common type of adverse events occurring in hospitalized patients, whereas an estimated 40-60% of these infections are thought to be preventable. Choice of regimen, administration timing or duration of antibiotic prophylaxis is reported to be inappropriate in approximately 25-50% of cases. We tried to evaluate an antibiotic administration pattern for surgical antibiotic prophylaxis in a teaching hospital. METHODS: This study was conducted at the general surgery and orthopedic wards of a teaching hospital affiliated with Mazandaran University of Medical Sciences. The medical records of admitted patients who underwent different surgical procedures were reviewed. Compliance was assessed with the recommendations of the American Society of Health-System Pharmacists' guidelines for every aspect of antibiotic prophylaxis. All data were coded and analyzed by SPSS16 software using Student's t-test and Chi-square test. FINDINGS: During 1 year, 759 patients who underwent different surgeries were included in the study. Mean age of patients was 32.02 +/ 18.79 years. Hand and foot fractures repair were the most frequent surgery types. About 56.4% of administered prophylactic antibiotics were in accordance with the American Society of Health System Pharmacists (ASHP) guidelines regarding prophylaxis indication. The most commonly antibiotic used was cefazolin and antibiotic choices were appropriate in 104 of 168 surgical procedures (62%). Gentamicin, metronidazole and ceftriaxone were the most frequently antibiotics that used inappropriately. Only in 100 of 168 procedures, duration was concordant with the ASHP guideline, whereas in 68 procedures, duration was longer than recommended time. In 98 procedures, the dose was lower and in one procedure, it was higher than recommended doses. CONCLUSION: Although such guidelines have been in place for many years, studies showed that much inappropriate antibiotic use as prophylaxis and poor adherence to guidelines are still major issues. It is essential for surgeons to be aware to consider the best antibiotic choices, dose and duration based on reliable guidelines for antibiotic prophylaxis. PMID- 25114940 TI - Efficacy of a local-drug delivery gel containing extracts of Quercus brantii and Coriandrum sativum as an adjunct to scaling and root planing in moderate chronic periodontitis patients. AB - OBJECTIVE: Recent advances in the field of alternative medicine introduced various herbal products for the treatment of periodontitis. The purpose of this study was to evaluate the effects of combined extracts from Quercus brantii and Coriandrum sativum on periodontal indices in adult periodontitis patients. METHODS: In this randomized, double-blinded clinical trial, performed in Isfahan Dental School in 2012, a new herbal medicament containing combined extracts from Q. brantii and C. sativum was formulated in the gel form for subgingival application. Following scaling and root planing (SRP), both herbal and placebo gels were delivered at the experimental and control sites, respectively. Periodontal pocket depth, clinical attachment level, papilla bleeding index, and plaque index were measured at baseline, 1 month and 3 months later. Both intra and inter-groups changes were registered. The obtained data were analyzed by SPSS software, using repeated measure analysis of variance, paired t-test, Mann Whitney, Friedman, and Wilcoxon tests. Differences with P < 0.05 were considered to be significant. FINDINGS: Both groups indicated statistically significant improvements in the periodontal indices (P < 0.05), but there were no significant differences between two study groups with this regard. CONCLUSION: The herbal gel does not have considerable advantages over SRP alone as an adjunct in periodontal treatment. PMID- 25114941 TI - Ceftriaxone induced drug rash with eosinophilia and systemic symptoms. AB - Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a drug reaction commonly occurring in association with aromatic anticonvulsants and allopurinol. It is characterized by triad of fever, skin eruption, and systemic involvement. DRESS is rare with beta-lactam antibiotics and even rarer with ceftriaxone. We describe a case of pneumonia who developed ceftriaxone-induced rash, bicytopenia, eosinophilia, transaminitis and was eventually diagnosed and managed successfully as a case of DRESS. PMID- 25114942 TI - Nudging by shaming, shaming by nudging. PMID- 25114943 TI - Harnessing the potential to quantify public preferences for healthcare priorities through citizens' juries. AB - Despite progress towards greater public engagement, questions about the optimal approach to access public preferences remain unanswered. We review two increasingly popular methods for engaging the public in healthcare priority setting and determining their preferences; the Citizens' Jury (CJ) and Discrete Choice Experiment (DCE). We discuss the theoretical framework from which each method is derived, its application in healthcare, and critique the information it can provide for decision-makers. We conclude that combining deliberation of an informed public via CJs and quantification of preferences using DCE methods, whilst it remains to be tested as an approach to engaging the public in priority setting, could potentially achieve much richer information than the application of either method in isolation. PMID- 25114944 TI - Factors affecting the technical efficiency of health systems: A case study of Economic Cooperation Organization (ECO) countries (2004-10). AB - BACKGROUND: Improving efficiency of health sector is of particular importance in all countries. To reach this end, it is paramount to measure the efficiency. On the other hand, there are many factors that affect the efficiency of health systems. This study aimed to measure the Technical Efficiency (TE) of health systems in Economic Cooperation Organization (ECO) countries during 2004-10 and to determine the factors affecting their TE. METHODS: This was a descriptive analytical and panel study. The required data were gathered using library and field studies, available statistics and international websites through completing data collection forms. In this study, the TE of health systems in 10 ECO countries was measured using their available data and Data Envelopment Analysis (DEA) through two approaches. The first approach used GDP per capita, education and smoking as its inputs and life expectancy and infant mortality rates as the outputs. The second approach, also, used the health expenditures per capita, the number of physicians per thousand people, and the number of hospital beds per thousand people as its inputs and life expectancy and under-5 mortality rates as the outputs. Then, the factors affecting the TE of health systems were determined using the panel data logit model. Excel 2010, Win4Deap 1.1.2 and Stata 11.0 were used to analyze the collected data. RESULTS: According to the first approach, the mean TE of health systems was 0.497 and based on the second one it was 0.563. Turkey and Turkmenistan had, respectively, the highest and lowest mean of efficiency. Also, the results of panel data logit model showed that only GDP per capita and health expenditures per capita had significant relationships with the TE of health systems. CONCLUSION: In order to maximize the TE of health systems, health policy-makers should pay special attention to the proper use of healthcare resources according to the people's needs, the appropriate management of the health system resources, allocating adequate budgets to the health sector, establishing an appropriate referral system to provide better public access to health services according to their income and needs, among many others. PMID- 25114945 TI - Prevalence and determinants of under-nutrition among children under six: a cross sectional survey in Fars province, Iran. AB - BACKGROUND: Childhood malnutrition as a major public health problem among children in developing countries can affect physical and intellectual growth and is also considered as a main cause of child morbidity and mortality. The objective of this study was to estimate the prevalence of under-nutrition and identify determinants of malnutrition among children under 6 years of age in Fars province, Iran. METHODS: This survey was conducted by house to house visit through multi-stage sampling in 30 cities of Fars province, during December 2012 to January 2013. A total of 15408 children, aged 0-6 years old, were studied for nutritional assessment in terms of underweight, stunting, and wasting. Also, socio-demographic measures were obtained from structured questionnaire. Backward stepwise logistic regression was used to relate underlying factors to the odds of under-nutrition indices. RESULTS: The rates of stunting, underweight, and wasting were 9.53, 9.66, and 8.19%, respectively. Male children were more stunted compared to females (OR= 1.41, CI: 1.26-1.58). Also, stunting was significantly associated with lower family income (OR= 3.21, CI: 1.17-8.85) and lower maternal education (OR= 0.80, CI: 0.64-0.98). Living in urban areas, and poor water supply were identified as significant risk factors of all three types of childhood under nutrition. Moreover, Khamse and Arab ethnic groups were more vulnerable to under nutrition. There was a suggestion that non-access to health services were associated with wasting (OR= 1.87, CI: 1.39-2.52) and also large family size was related to underweight (OR= 1.35, CI: 1.10-1.65). CONCLUSION: The prevalence of under-nutrition in the study population was categorized in low levels. However, planning the public preventive strategies can help to control childhood under nutrition according to underlying factors of malnutrition in the study population including gender, settlement area, family size, ethnicity, family income, maternal education, health services, and also safe water supply. PMID- 25114946 TI - Factors influencing healthcare service quality. AB - BACKGROUND: The main purpose of this study was to identify factors that influence healthcare quality in the Iranian context. METHODS: Exploratory in-depth individual and focus group interviews were conducted with 222 healthcare stakeholders including healthcare providers, managers, policy-makers, and payers to identify factors affecting the quality of healthcare services provided in Iranian healthcare organisations. RESULTS: Quality in healthcare is a production of cooperation between the patient and the healthcare provider in a supportive environment. Personal factors of the provider and the patient, and factors pertaining to the healthcare organisation, healthcare system, and the broader environment affect healthcare service quality. Healthcare quality can be improved by supportive visionary leadership, proper planning, education and training, availability of resources, effective management of resources, employees and processes, and collaboration and cooperation among providers. CONCLUSION: This article contributes to healthcare theory and practice by developing a conceptual framework that provides policy-makers and managers a practical understanding of factors that affect healthcare service quality. PMID- 25114947 TI - Technical efficiency of teaching hospitals in Iran: the use of Stochastic Frontier Analysis, 1999-2011. AB - BACKGROUND: Hospitals are highly resource-dependent settings, which spend a large proportion of healthcare financial resources. The analysis of hospital efficiency can provide insight into how scarce resources are used to create health values. This study examines the Technical Efficiency (TE) of 12 teaching hospitals affiliated with Tehran University of Medical Sciences (TUMS) between 1999 and 2011. METHODS: The Stochastic Frontier Analysis (SFA) method was applied to estimate the efficiency of TUMS hospitals. A best function, referred to as output and input parameters, was calculated for the hospitals. Number of medical doctors, nurses, and other personnel, active beds, and outpatient admissions were considered as the input variables and number of inpatient admissions as an output variable. RESULTS: The mean level of TE was 59% (ranging from 22 to 81%). During the study period the efficiency increased from 61 to 71%. Outpatient admission, other personnel and medical doctors significantly and positively affected the production (P< 0.05). Concerning the Constant Return to Scale (CRS), an optimal production scale was found, implying that the productions of the hospitals were approximately constant. CONCLUSION: Findings of this study show a remarkable waste of resources in the TUMS hospital during the decade considered. This warrants policy-makers and top management in TUMS to consider steps to improve the financial management of the university hospitals. PMID- 25114948 TI - Addressing diabetes at the crossroads of global pandemic and regional culture: Comment on "The curse of wealth - Middle Eastern countries need to address the rapidly rising burden of diabetes". AB - As diabetes and obesity rates continue to climb at astronomical rates in the Middle East, future generations are at an even greater risk for diabetes and the associated complications. Many factors are at play and it is clear that creative solutions are needed to retool provider resources in the Middle East towards prevention of diabetes and its complications while leveraging technology to maximize outreach within the accepted cultural norms. Only by building the capacity to address the current diabetes burden as well focusing on prevention for the future, can Middle East countries create a strong infrastructure for a successful future. PMID- 25114949 TI - Global health politics: neither solidarity nor policy: Comment on "Globalization and the diffusion of ideas: why we should acknowledge the roots of mainstream ideas in global health". AB - The global health agenda has been dominating the current global health policy debate. Furthermore, it has compelled countries to embrace strategies for tackling health inequalities in a wide range of public health areas. The article by Robert and colleagues highlights that although globalization has increased opportunities to share and spread ideas, there is still great asymmetry of power according to the countries' economic and political development. It also emphasizes how policy diffusion from High Income Countries (HICs) to Low- and Middle-Income Countries (LMICs) have had flaws at understanding their political, economic, and cultural backgrounds while they are pursuing knowledge translation. Achieving a fair global health policy diffusion of ideas would imply a call for a renewal on political elites worldwide at coping global health politics. Accordingly, moving towards fairness in disseminating global health ideas should be driven by politics not only as one of the social determinants of health, but the main determinant of health and well-being among-and within-societies. PMID- 25114950 TI - The search for underlying principles of health impact assessment: progress and prospects: Comment on "Investigating underlying principles to guide health impact assessment". AB - Health Impact Assessment (HIA) is a relatively young field of endeavour, and hence, future progress will depend on the planning, implementation and rigorous evaluation of additional HIAs of projects, programmes and policies the world over. In the June 2014 issue of the International Journal of Health Policy and Management, Fakhri and colleagues investigated underlying principles of HIA through a comprehensive review of the literature and expert consultation. With an emphasis on the Islamic Republic of Iran, the authors identified multiple issues that are relevant for guiding HIA practice. At the same time, the study unravelled current shortcomings in the understanding and definition of HIA principles and best practice at national, regional, and global levels. In this commentary we scrutinise the research presented, highlight strengths and limitations, and discuss the findings in the context of other recent attempts to guide HIA. PMID- 25114951 TI - Global health diplomacy: a 'Deus ex Machina' for international development and relations: Comment on "A Ghost in the Machine? Politics in Global Health Policy". PMID- 25114953 TI - Gas production strategy of underground coal gasification based on multiple gas sources. AB - To lower stability requirement of gas production in UCG (underground coal gasification), create better space and opportunities of development for UCG, an emerging sunrise industry, in its initial stage, and reduce the emission of blast furnace gas, converter gas, and coke oven gas, this paper, for the first time, puts forward a new mode of utilization of multiple gas sources mainly including ground gasifier gas, UCG gas, blast furnace gas, converter gas, and coke oven gas and the new mode was demonstrated by field tests. According to the field tests, the existing power generation technology can fully adapt to situation of high hydrogen, low calorific value, and gas output fluctuation in the gas production in UCG in multiple-gas-sources power generation; there are large fluctuations and air can serve as a gasifying agent; the gas production of UCG in the mode of both power and methanol based on multiple gas sources has a strict requirement for stability. It was demonstrated by the field tests that the fluctuations in gas production in UCG can be well monitored through a quality control chart method. PMID- 25114954 TI - Free convection nanofluid flow in the stagnation-point region of a three dimensional body. AB - Analytical results are presented for a steady three-dimensional free convection flow in the stagnation point region over a general curved isothermal surface placed in a nanofluid. The momentum equations in x- and y-directions, energy balance equation, and nanoparticle concentration equation are reduced to a set of four fully coupled nonlinear differential equations under appropriate similarity transformations. The well known technique optimal homotopy analysis method (OHAM) is used to obtain the exact solution explicitly, whose convergence is then checked in detail. Besides, the effects of the physical parameters, such as the Lewis number, the Brownian motion parameter, the thermophoresis parameter, and the buoyancy ratio on the profiles of velocities, temperature, and concentration, are studied and discussed. Furthermore the local skin friction coefficients in x- and y-directions, the local Nusselt number, and the local Sherwood number are examined for various values of the physical parameters. PMID- 25114952 TI - Andrographolide inhibits nuclear factor-kappaB activation through JNK-Akt-p65 signaling cascade in tumor necrosis factor-alpha-stimulated vascular smooth muscle cells. AB - Critical vascular inflammation leads to vascular dysfunction and cardiovascular diseases, including abdominal aortic aneurysms, hypertension, and atherosclerosis. Andrographolide is the most active and critical constituent isolated from the leaves of Andrographis paniculata, a herbal medicine widely used for treating anti-inflammation in Asia. In this study, we investigated the mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-alpha (TNF-alpha). Treating TNF-alpha-stimulated VSMCs with andrographolide suppressed the expression of inducible nitric oxide synthase in a concentration-dependent manner. A reduction in TNF-alpha-induced c-Jun N-terminal kinase (JNK), Akt, and p65 phosphorylation was observed in andrographolide-treated VSMCs. However, andrographolide affected neither IkappaBalpha degradation nor p38 mitogen activated protein kinase or extracellular signal-regulated kinase 1/2 phosphorylation under these conditions. Both treatment with LY294002, a phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK inhibitor, markedly reversed the andrographolide-mediated inhibition of p65 phosphorylation. In addition, LY294002 and SP600125 both diminished Akt phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These results collectively suggest that therapeutic interventions using andrographolide can benefit the treatment of vascular inflammatory diseases, and andrographolide mediated inhibition of NF-kappaB activity in TNF-alpha-stimulated VSMCs occurs through the JNK-Akt-p65 signaling cascade, an IkappaBalpha-independent mechanism. PMID- 25114955 TI - Moving object localization using optical flow for pedestrian detection from a moving vehicle. AB - This paper presents a pedestrian detection method from a moving vehicle using optical flows and histogram of oriented gradients (HOG). A moving object is extracted from the relative motion by segmenting the region representing the same optical flows after compensating the egomotion of the camera. To obtain the optical flow, two consecutive images are divided into grid cells 14 * 14 pixels; then each cell is tracked in the current frame to find corresponding cell in the next frame. Using at least three corresponding cells, affine transformation is performed according to each corresponding cell in the consecutive images, so that conformed optical flows are extracted. The regions of moving object are detected as transformed objects, which are different from the previously registered background. Morphological process is applied to get the candidate human regions. In order to recognize the object, the HOG features are extracted on the candidate region and classified using linear support vector machine (SVM). The HOG feature vectors are used as input of linear SVM to classify the given input into pedestrian/nonpedestrian. The proposed method was tested in a moving vehicle and also confirmed through experiments using pedestrian dataset. It shows a significant improvement compared with original HOG using ETHZ pedestrian dataset. PMID- 25114956 TI - Changes in stream peak flow and regulation in Naoli River watershed as a result of wetland loss. AB - Hydrology helps determine the character of wetlands; wetlands, in turn, regulate water flow, which influences regional hydrology. To understand these dynamics, we studied the Naoli basin where, from 1954 to 2005, intensive marshland cultivation took place, and the watershed's wetland area declined from 94.4 * 10(4)ha to 17.8 * 10(4)ha. More than 80% of the wetland area loss was due to conversion to farmland, especially from 1976 to 1986. The processes of transforming wetlands to cultivated land in the whole Naoli basin and subbasins can be described using a first order exponential decay model. To quantify the effects of wetlands cultivation, we analyzed daily rainfall and streamflow data measured from 1955 to 2005 at two stations (Baoqing Station and Caizuizi Station). We defined a streamflow regulation index (SRI) and applied a Mann-Kendall-Sneyers test to further analyze the data. As the wetland area decreased, the peak streamflow at the Caizuizi station increased, and less precipitation generated heavier peak flows, as the runoff was faster than before. The SRI from 1959 to 2005 showed an increasing trend; the SRI rate of increase was 0.05/10a, demonstrating that the watershed's regulation of streamflow regulation was declined as the wetlands disappeared. PMID- 25114957 TI - Fractal analysis of laplacian pyramidal filters applied to segmentation of soil images. AB - The laplacian pyramid is a well-known technique for image processing in which local operators of many scales, but identical shape, serve as the basis functions. The required properties to the pyramidal filter produce a family of filters, which is unipara metrical in the case of the classical problem, when the length of the filter is 5. We pay attention to gaussian and fractal behaviour of these basis functions (or filters), and we determine the gaussian and fractal ranges in the case of single parameter a. These fractal filters loose less energy in every step of the laplacian pyramid, and we apply this property to get threshold values for segmenting soil images, and then evaluate their porosity. Also, we evaluate our results by comparing them with the Otsu algorithm threshold values, and conclude that our algorithm produce reliable test results. PMID- 25114958 TI - Real-time safety risk assessment based on a real-time location system for hydropower construction sites. AB - The concern for workers' safety in construction industry is reflected in many studies focusing on static safety risk identification and assessment. However, studies on real-time safety risk assessment aimed at reducing uncertainty and supporting quick response are rare. A method for real-time safety risk assessment (RTSRA) to implement a dynamic evaluation of worker safety states on construction site has been proposed in this paper. The method provides construction managers who are in charge of safety with more abundant information to reduce the uncertainty of the site. A quantitative calculation formula, integrating the influence of static and dynamic hazards and that of safety supervisors, is established to link the safety risk of workers with the locations of on-site assets. By employing the hidden Markov model (HMM), the RTSRA provides a mechanism for processing location data provided by the real-time location system (RTLS) and analyzing the probability distributions of different states in terms of false positives and negatives. Simulation analysis demonstrated the logic of the proposed method and how it works. Application case shows that the proposed RTSRA is both feasible and effective in managing construction project safety concerns. PMID- 25114959 TI - A high-speed and low-offset dynamic latch comparator. AB - Circuit intricacy, speed, low-offset voltage, and resolution are essential factors for high-speed applications like analog-to-digital converters (ADCs). The comparator circuit with preamplifier increases the power dissipation, as it requires higher amount of currents than the latch circuitry. In this research, a novel topology of dynamic latch comparator is illustrated, which is able to provide high speed, low offset, and high resolution. Moreover, the circuit is able to reduce the power dissipation as the topology is based on latch circuitry. The cross-coupled circuit mechanism with the regenerative latch is employed for enhancing the dynamic latch comparator performance. In addition, input-tracking phase is used to reduce the offset voltage. The Monte-Carlo simulation results for the designed comparator in 0.18 MUm CMOS process show that the equivalent input-referred offset voltage is 720 MUV with 3.44 mV standard deviation. The simulated result shows that the designed comparator has 8-bit resolution and dissipates 158.5 MUW of power under 1.8 V supply while operating with a clock frequency of 50 MHz. In addition, the proposed dynamic latch comparator has a layout size of 148.80 MUm * 59.70 MUm. PMID- 25114960 TI - Cytotoxic activities of flavonoids from Centaurea scoparia. AB - Phytochemical studies on the ethanolic extract of the aerial parts of Centaurea scoparia led to the isolation of two new flavonoids, 3',4'-dihydroxy-(3'',4'' dihydro-3''-hydroxy-4''-acetoxy)-2'',2''-dimethylpyrano-(5'',6'':7,8)-flavone-3-O beta -D-glucopyranoside (1) and 3,3',4'-trihydroxy-(3'',4''-dihydro-3'',4'' dihydroxy)-2'',2''-dimethylpyrano-(5'',6'':7,8)-flavone (2), along with eight known flavonoids isolated for the first time from this plant, cynaroside (3), Apigetrin (4), centaureidin (5), oroxylin A (6), 5,7-dihydroxy-3',4',5' trimethoxyflavone (7), atalantoflavone (8), 5-hydroxy-3',4',8-trimethoxy-2'',2'' dimethylpyrano (5'',6'':6,7)-flavone (9), and 3',4',5,8-tetramethoxy-2'',2'' dimethylpyrano (5'',6'':6,7)-flavone (10). The structures of the isolated compounds were elucidated by means of spectroscopic tools including 1D and 2D NMR, UV, IR, and mass spectroscopy. Cytotoxic activities of the isolated compounds were evaluated against human cervical carcinoma HeLa, human hepatocellular carcinoma HepG2, and human breast carcinoma MCF-7. Compound 2 was the most potent cytotoxic agent against HeLa cells with an IC50 0.079 MUM. PMID- 25114961 TI - Research on radiation characteristic of plasma antenna through FDTD method. AB - The radiation characteristic of plasma antenna is investigated by using the finite-difference time-domain (FDTD) approach in this paper. Through using FDTD method, we study the propagation of electromagnetic wave in free space in stretched coordinate. And the iterative equations of Maxwell equation are derived. In order to validate the correctness of this method, we simulate the process of electromagnetic wave propagating in free space. Results show that electromagnetic wave spreads out around the signal source and can be absorbed by the perfectly matched layer (PML). Otherwise, we study the propagation of electromagnetic wave in plasma by using the Boltzmann-Maxwell theory. In order to verify this theory, the whole process of electromagnetic wave propagating in plasma under one-dimension case is simulated. Results show that Boltzmann-Maxwell theory can be used to explain the phenomenon of electromagnetic wave propagating in plasma. Finally, the two-dimensional simulation model of plasma antenna is established under the cylindrical coordinate. And the near-field and far-field radiation pattern of plasma antenna are obtained. The experiments show that the variation of electron density can introduce the change of radiation characteristic. PMID- 25114962 TI - Toughness condition for a graph to be a fractional (g, f, n)-critical deleted graph. AB - A graph G is called a fractional (g, f)-deleted graph if G - {e} admits a fractional (g, f)-factor for any e ? E(G). A graph G is called a fractional (g, f, n)-critical deleted graph if, after deleting any n vertices from G, the resulting graph is still a fractional (g, f)-deleted graph. The toughness, as the parameter for measuring the vulnerability of communication networks, has received significant attention in computer science. In this paper, we present the relationship between toughness and fractional (g, f, n)-critical deleted graphs. It is determined that G is fractional (g, f, n)-critical deleted if t(G) >= ((b (2) - 1 + bn)/a). PMID- 25114963 TI - Riemann boundary value problem for triharmonic equation in higher space. AB - We mainly deal with the boundary value problem for triharmonic function with value in a universal Clifford algebra: Delta(3)[u](x) = 0, x ? R (n)??Omega, u (+)(x) = u (-)(x)G(x) + g(x), x ? ?Omega, (D (j) u)(+)(x) = (D (j) u)(-)(x)A j + f j (x), x ? ?Omega, u(infinity) = 0, where (j = 1,..., 5) ?Omega is a Lyapunov surface in R (n) , D = ? k=1 (n) e k (?/?x k) is the Dirac operator, and u(x) = ? A e A u A (x) are unknown functions with values in a universal Clifford algebra Cl(V n,n). Under some hypotheses, it is proved that the boundary value problem has a unique solution. PMID- 25114965 TI - A novel clustering algorithm for mobile ad hoc networks based on determination of virtual links' weight to increase network stability. AB - The stability of clusters is a serious issue in mobile ad hoc networks. Low stability of clusters may lead to rapid failure of clusters, high energy consumption for reclustering, and decrease in the overall network stability in mobile ad hoc network. In order to improve the stability of clusters, weight based clustering algorithms are utilized. However, these algorithms only use limited features of the nodes. Thus, they decrease the weight accuracy in determining node's competency and lead to incorrect selection of cluster heads. A new weight-based algorithm presented in this paper not only determines node's weight using its own features, but also considers the direct effect of feature of adjacent nodes. It determines the weight of virtual links between nodes and the effect of the weights on determining node's final weight. By using this strategy, the highest weight is assigned to the best choices for being the cluster heads and the accuracy of nodes selection increases. The performance of new algorithm is analyzed by using computer simulation. The results show that produced clusters have longer lifetime and higher stability. Mathematical simulation shows that this algorithm has high availability in case of failure. PMID- 25114964 TI - Forest fire smoke layers observed in the free troposphere over Portugal with a multiwavelength Raman lidar: optical and microphysical properties. AB - Vertically resolved optical and microphysical properties of biomass burning aerosols, measured in 2011 with a multiwavelength Raman lidar, are presented. The transportation time, within 1-2 days (or less), pointed towards the presence of relatively fresh smoke particles over the site. Some strong layers aloft were observed with particle backscatter and extinction coefficients (at 355 nm) greater than 5 Mm(-1)sr(-1) and close to 300 Mm(-1), respectively. The particle intensive optical properties showed features different from the ones reported for aged smoke, but rather consistent with fresh smoke. The Angstrom exponents were generally high, mainly above 1.4, indicating a dominating accumulation mode. Weak depolarization values, as shown by the small depolarization ratio of 5% or lower, were measured. Furthermore, the lidar ratio presented no clear wavelength dependency. The inversion of the lidar signals provided a set of microphysical properties including particle effective radius below 0.2 MUm, which is less than values previously observed for aged smoke particles. Real and imaginary parts of refractive index of about 1.5-1.6 and 0.02i, respectively, were derived. The single scattering albedo was in the range between 0.85 and 0.93; these last two quantities indicate the nonnegligible absorbing characteristics of the observed particles. PMID- 25114966 TI - Combining digital watermarking and fingerprinting techniques to identify copyrights for color images. AB - This paper presents a copyright identification scheme for color images that takes advantage of the complementary nature of watermarking and fingerprinting. It utilizes an authentication logo and the extracted features of the host image to generate a fingerprint, which is then stored in a database and also embedded in the host image to produce a watermarked image. When a dispute over the copyright of a suspect image occurs, the image is first processed by watermarking. If the watermark can be retrieved from the suspect image, the copyright can then be confirmed; otherwise, the watermark then serves as the fingerprint and is processed by fingerprinting. If a match in the fingerprint database is found, then the suspect image will be considered a duplicated one. Because the proposed scheme utilizes both watermarking and fingerprinting, it is more robust than those that only adopt watermarking, and it can also obtain the preliminary result more quickly than those that only utilize fingerprinting. The experimental results show that when the watermarked image suffers slight attacks, watermarking alone is enough to identify the copyright. The results also show that when the watermarked image suffers heavy attacks that render watermarking incompetent, fingerprinting can successfully identify the copyright, hence demonstrating the effectiveness of the proposed scheme. PMID- 25114967 TI - A procedure for extending input selection algorithms to low quality data in modelling problems with application to the automatic grading of uploaded assignments. AB - When selecting relevant inputs in modeling problems with low quality data, the ranking of the most informative inputs is also uncertain. In this paper, this issue is addressed through a new procedure that allows the extending of different crisp feature selection algorithms to vague data. The partial knowledge about the ordinal of each feature is modelled by means of a possibility distribution, and a ranking is hereby applied to sort these distributions. It will be shown that this technique makes the most use of the available information in some vague datasets. The approach is demonstrated in a real-world application. In the context of massive online computer science courses, methods are sought for automatically providing the student with a qualification through code metrics. Feature selection methods are used to find the metrics involved in the most meaningful predictions. In this study, 800 source code files, collected and revised by the authors in classroom Computer Science lectures taught between 2013 and 2014, are analyzed with the proposed technique, and the most relevant metrics for the automatic grading task are discussed. PMID- 25114969 TI - SER performance of enhanced spatial multiplexing codes with ZF/MRC receiver in time-varying Rayleigh fading channels. AB - We propose enhanced spatial multiplexing codes (E-SMCs) to enable various encoding rates. The symbol error rate (SER) performance of the E-SMC is investigated when zero-forcing (ZF) and maximal-ratio combining (MRC) techniques are used at a receiver. The proposed E-SMC allows a transmitted symbol to be repeated over time to achieve further diversity gain at the cost of the encoding rate. With the spatial correlation between transmit antennas, SER equations for M ary QAM and PSK constellations are derived by using a moment generating function (MGF) approximation of a signal-to-noise ratio (SNR), based on the assumption of independent zero-forced SNRs. Analytic and simulated results are compared for time-varying and spatially correlated Rayleigh fading channels that are modelled as first-order Markovian channels. Furthermore, we can find an optimal block length for the E-SMC that meets a required SER. PMID- 25114968 TI - Exploring a QoS driven scheduling approach for peer-to-peer live streaming systems with network coding. AB - Most large-scale peer-to-peer (P2P) live streaming systems use mesh to organize peers and leverage pull scheduling to transmit packets for providing robustness in dynamic environment. The pull scheduling brings large packet delay. Network coding makes the push scheduling feasible in mesh P2P live streaming and improves the efficiency. However, it may also introduce some extra delays and coding computational overhead. To improve the packet delay, streaming quality, and coding overhead, in this paper are as follows. we propose a QoS driven push scheduling approach. The main contributions of this paper are: (i) We introduce a new network coding method to increase the content diversity and reduce the complexity of scheduling; (ii) we formulate the push scheduling as an optimization problem and transform it to a min-cost flow problem for solving it in polynomial time; (iii) we propose a push scheduling algorithm to reduce the coding overhead and do extensive experiments to validate the effectiveness of our approach. Compared with previous approaches, the simulation results demonstrate that packet delay, continuity index, and coding ratio of our system can be significantly improved, especially in dynamic environments. PMID- 25114971 TI - Combinatorial efficiency evaluation: the knapsack problem in data envelopment analysis. AB - The traditional data envelopment analysis (DEA) literatures generally concentrated on the efficiency evaluation of single decision making unit (DMU). However, in many practical problems, the decision makers are required to choose a number of DMUs instead of a single one from the DMUs set. Therefore, it is necessary to study the combinatorial efficiency evaluation problem which can be illustrated as a knapsack problem naturally. It is indicated that the basic model proposed by Cook and Green may have some drawbacks and a modified model, which is combined with the super efficiency model, is proposed in this paper. What is more, our proposed model is more persuasive to the decision makers because it is able to provide a unique best combination of DMUs. An adapted local search algorithm is developed as a solver of this problem. Finally, numerical examples are provided to examine the validity of our proposed model and the adapted local search algorithm. PMID- 25114973 TI - Potential rainwater harvesting improvement using advanced remote sensing applications. AB - The amount of water on earth is the same and only the distribution and the reallocation of water forms are altered in both time and space. To improve the rainwater harvesting a better understanding of the hydrological cycle is mandatory. Clouds are major component of the hydrological cycle; therefore, clouds distribution is the keystone of better rainwater harvesting. Remote sensing technology has shown robust capabilities in resolving challenges of water resource management in arid environments. Soil moisture content and cloud average distribution are essential remote sensing applications in extracting information of geophysical, geomorphological, and meteorological interest from satellite images. Current research study aimed to map the soil moisture content using recent Landsat 8 images and to map cloud average distribution of the corresponding area using 59 MERIS satellite imageries collected from January 2006 to October 2011. Cloud average distribution map shows specific location in the study area where it is always cloudy all the year and the site corresponding soil moisture content map came in agreement with cloud distribution. The overlay of the two previously mentioned maps over the geological map of the study area shows potential locations for better rainwater harvesting. PMID- 25114970 TI - The p85 regulatory subunit of PI3K mediates cAMP-PKA and insulin biological effects on MCF-7 cell growth and motility. AB - Recent studies have shown that hyperinsulinemia may increase the cancer risk. Moreover, many tumors demonstrate an increased activation of IR signaling pathways. Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action. In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes, insulin-mediated PI3K activation regulates cell survival, growth, and motility. Although the involvement of the regulatory subunit of PI3K (p85alpha (PI3K)) in insulin signal transduction has been extensively studied, the function of its N terminus remains elusive. It has been identified as a serine (S83) in the p85alpha (PI3K) that is phosphorylated by protein kinase A (PKA). To determine the molecular mechanism linking PKA to insulin-mediated PI3K activation, we used p85alpha (PI3K) mutated forms to prevent phosphorylation (p85A) or to mimic the phosphorylated residue (p85D). We demonstrated that phosphorylation of p85alpha (PI3K)S83 modulates the formation of the p85alpha (PI3K)/IRS-1 complex and its subcellular localization influencing the kinetics of the insulin signaling both on MAPK-ERK and AKT pathways. Furthermore, the p85alpha (PI3K)S83 phosphorylation plays a central role in the control of insulin-mediated cell proliferation, cell migration, and adhesion. This study highlights the p85alpha (PI3K)S83 role as a key regulator of cell proliferation and motility induced by insulin in MCF-7 cells breast cancer model. PMID- 25114972 TI - Service life assessment of historical building envelopes constructed using different types of sandstone: a computational analysis based on experimental input data. AB - Service life assessment of three historical building envelopes constructed using different types of sandstone is presented. At first, experimental measurements of material parameters of sandstones are performed to provide the necessary input data for a subsequent computational analysis. In the second step, the moisture and temperature fields across the studied envelopes are calculated for a representative period of time. The computations are performed using dynamic climatic data as the boundary conditions on the exterior side of building envelope. The climatic data for three characteristic localities are experimentally determined by the Czech Hydrometeorological Institute and contain hourly values of temperature, relative humidity, rainfalls, wind velocity and direction, and sun radiation. Using the measured durability properties of the analyzed sandstones and the calculated numbers of freeze/thaw cycles under different climatic conditions, the service life of the investigated building envelopes is assessed. The obtained results show that the climatic conditions can play a very significant role in the service life assessment of historical buildings, even in the conditions of such a small country as the Czech Republic. In addition, the investigations reveal the importance of the material characteristics of sandstones, in particular the hygric properties, on their service life in a structure. PMID- 25114975 TI - Security techniques for prevention of rank manipulation in social tagging services including robotic domains. AB - With smartphone distribution becoming common and robotic applications on the rise, social tagging services for various applications including robotic domains have advanced significantly. Though social tagging plays an important role when users are finding the exact information through web search, reliability and semantic relation between web contents and tags are not considered. Spams are making ill use of this aspect and put irrelevant tags deliberately on contents and induce users to advertise contents when they click items of search results. Therefore, this study proposes a detection method for tag-ranking manipulation to solve the problem of the existing methods which cannot guarantee the reliability of tagging. Similarity is measured for ranking the grade of registered tag on the contents, and weighted values of each tag are measured by means of synonym relevance, frequency, and semantic distances between tags. Lastly, experimental evaluation results are provided and its efficiency and accuracy are verified through them. PMID- 25114974 TI - Expression of a splice variant of CYP26B1 in betel quid-related oral cancer. AB - Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1 carcinogen that exhibits the potential to induce adverse health effects. Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the development of oral pharyngeal cancers. We investigated whether a splice variant of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell viability in a dose-dependent manner. In vitro and in vivo studies were conducted to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice variant exhibited lower expression than did full-length CYP26B1 in the human gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1 splice variant was observed in human oral cancer tissue compared with adjacent normal tissue, and increased expression was observed in patients at a late tumor stage. Our results suggested that the CYP26B1 splice variant is associated with the occurrence of BQ-related oral cancer. PMID- 25114977 TI - An efficient image compressor for charge coupled devices camera. AB - Recently, the discrete wavelet transforms- (DWT-) based compressor, such as JPEG2000 and CCSDS-IDC, is widely seen as the state of the art compression scheme for charge coupled devices (CCD) camera. However, CCD images project on the DWT basis to produce a large number of large amplitude high-frequency coefficients because these images have a large number of complex texture and contour information, which are disadvantage for the later coding. In this paper, we proposed a low-complexity posttransform coupled with compressing sensing (PT-CS) compression approach for remote sensing image. First, the DWT is applied to the remote sensing image. Then, a pair base posttransform is applied to the DWT coefficients. The pair base are DCT base and Hadamard base, which can be used on the high and low bit-rate, respectively. The best posttransform is selected by the l p -norm-based approach. The posttransform is considered as the sparse representation stage of CS. The posttransform coefficients are resampled by sensing measurement matrix. Experimental results on on-board CCD camera images show that the proposed approach significantly outperforms the CCSDS-IDC-based coder, and its performance is comparable to that of the JPEG2000 at low bit rate and it does not have the high excessive implementation complexity of JPEG2000. PMID- 25114976 TI - 3D analysis of D-RaCe and self-adjusting file in removing filling materials from curved root canals instrumented and filled with different techniques. AB - The aim of this study was to compare the efficacy of D-RaCe files and a self adjusting file (SAF) system in removing filling material from curved root canals instrumented and filled with different techniques by using microcomputed tomography (micro-CT). The mesial roots of 20 extracted mandibular first molars were used. Root canals (mesiobuccal and mesiolingual) were instrumented with SAF or Revo-S. The canals were then filled with gutta-percha and AH Plus sealer using cold lateral compaction or thermoplasticized injectable techniques. The root fillings were first removed with D-RaCe (Step 1), followed by Step 2, in which a SAF system was used to remove the residual fillings in all groups. Micro-CT scans were used to measure the volume of residual filling after root canal filling, reinstrumentation with D-RaCe (Step 1), and reinstrumentation with SAF (Step 2). Data were analyzed using Wilcoxon and Kruskal-Wallis tests. There were no statistically significant differences between filling techniques in the canals instrumented with SAF (P = 0.292) and Revo-S (P = 0.306). The amount of remaining filling material was similar in all groups (P = 0.363); all of the instrumentation techniques left filling residue inside the canals. However, the additional use of SAF was more effective than using D-RaCe alone. PMID- 25114978 TI - Density-based penalty parameter optimization on C-SVM. AB - The support vector machine (SVM) is one of the most widely used approaches for data classification and regression. SVM achieves the largest distance between the positive and negative support vectors, which neglects the remote instances away from the SVM interface. In order to avoid a position change of the SVM interface as the result of an error system outlier, C-SVM was implemented to decrease the influences of the system's outliers. Traditional C-SVM holds a uniform parameter C for both positive and negative instances; however, according to the different number proportions and the data distribution, positive and negative instances should be set with different weights for the penalty parameter of the error terms. Therefore, in this paper, we propose density-based penalty parameter optimization of C-SVM. The experiential results indicated that our proposed algorithm has outstanding performance with respect to both precision and recall. PMID- 25114979 TI - The axioms independence of pseudo-weak-R0 algebras and filters. AB - The most simplified axiom systems of pseudo-weak-R0 algebras and pseudo-R0 algebras are obtained, and the mutually independence of axioms is proved. We introduce the notions of filters and normal filters in pseudo-weak-R0 algebras. The structures and properties of the generated filters and generated normal filters in pseudo-weak-R0 algebras are obtained. These can be seen as noncommutative generalizations of the corresponding ones in weak-R0 algebras. PMID- 25114980 TI - Identification of the causative disease of intermittent claudication through walking motion analysis: feature analysis and differentiation. AB - Intermittent claudication is a walking symptom. Patients with intermittent claudication experience lower limb pain after walking for a short time. However, rest relieves the pain and allows the patient to walk again. Unfortunately, this symptom predominantly arises from not 1 but 2 different diseases: LSS (lumber spinal canal stenosis) and PAD (peripheral arterial disease). Patients with LSS can be subdivided by the affected vertebra into 2 main groups: L4 and L5. It is clinically very important to determine whether patients with intermittent claudication suffer from PAD, L4, or L5. This paper presents a novel SVM- (support vector machine-) based methodology for such discrimination/differentiation using minimally required data, simple walking motion data in the sagittal plane. We constructed a simple walking measurement system that is easy to set up and calibrate and suitable for use by nonspecialists in small spaces. We analyzed the obtained gait patterns and derived input parameters for SVM that are also visually detectable and medically meaningful/consistent differentiation features. We present a differentiation methodology utilizing an SVM classifier. Leave-one-out cross-validation of differentiation/classification by this method yielded a total accuracy of 83%. PMID- 25114981 TI - Models for 31-mode PVDF energy harvester for wearable applications. AB - Currently, wearable electronics are increasingly widely used, leading to an increasing need of portable power supply. As a clean and renewable power source, piezoelectric energy harvester can transfer mechanical energy into electric energy directly, and the energy harvester based on polyvinylidene difluoride (PVDF) operating in 31-mode is appropriate to harvest energy from human motion. This paper established a series of theoretical models to predict the performance of 31-mode PVDF energy harvester. Among them, the energy storage one can predict the collected energy accurately during the operation of the harvester. Based on theoretical study and experiments investigation, two approaches to improve the energy harvesting performance have been found. Furthermore, experiment results demonstrate the high accuracies of the models, which are better than 95%. PMID- 25114982 TI - Skin cancer by state and territory. AB - There is a paucity of Australian state-based data on the incidence of non melanoma skin cancer (NMSC). Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin are not notifiable diseases and are not collected by the state and territory cancer registries. In a 2002 survey, the Australian age standardised incidence per 100,000 persons for NMSC was 1170 (BCC 884, SCC 387), with a higher incidence in the northern latitudes. PMID- 25114983 TI - The role of risk tools in diagnosing cancer in primary care. AB - BACKGROUND: Diagnosing cancer on the basis of a patient's symptoms and risk factors is a core role for general practice. Equally, as part of a cost-effective health system, GPs should avoid over-investigation or referral of patients who are very unlikely to have cancer. Diagnosing cancer in primary care is not straightforward because many of the symptoms of cancer have more common benign causes. OBJECTIVE: The aim of this article is to review the use of risk tools for diagnosing cancer in primary care. DISCUSSION: Certain cancers, such as lung, pancreas, ovary and myeloma, are particularly challenging to diagnose early. National guidelines exist to support identification of patients who are more likely to have an undiagnosed cancer but these list single symptoms as so-called 'red flags'. Validated risk tools, developed in general practice, exist that predict cancer diagnosis on the basis of patterns of symptoms and risk factors. These tools might prove useful in supporting cancer diagnosis in general practice and also reducing investigation of patients at very low risk of cancer. PMID- 25114984 TI - End-of-life care for patients with cancer. AB - BACKGROUND: End-of-life care is a core role of general practice. Patients with disseminated cancer have rapidly escalating needs at the end of life that are usually predictable and, therefore, planning for future needs is possible. Care planning and working with specialist palliative care colleagues improves patient outcomes. OBJECTIVE: The aim of this article is to provide an overview of end-of life care for patients with cancer, including evidence supporting the involvement of general practitioners (GPs). DISCUSSION: Care planning is predicated on understanding the patient's wishes about how care should be conducted and ensuring the plan conforms to these wishes. Not all GPs are willing to undertake palliative care, often because of a sense of inadequate knowledge, confidence and support. The more palliative care is undertaken, however, the more confident practitioners feel. Therefore, starting to treat end-of-life patients early in a GP's career is important, and making use of the considerable resources available will assist in building knowledge and confidence. Systematically caring for carers might be a way of introducing GPs to the care of patients with cancer at the end of life. PMID- 25114985 TI - Cancer survivorship--the role of the GP. AB - BACKGROUND: Improvements in cancer detection, treatment and an ageing population mean that there are increasing numbers of people living with and beyond cancer. Current hospital-centred models of cancer follow-up have tended to focus on detection of cancer recurrence, which may result in significant unmet needs, particularly psychosocial needs. OBJECTIVE: This paper discusses the evidence from previous studies of primary care involvement in cancer survivorship and key areas to consider in the follow-up care for common cancers. DISCUSSION: General practice has an important role in the holistic care of cancer survivors and could take on an expanded role in cancer follow-up. PMID- 25114986 TI - Advance care planning. AB - BACKGROUND: Good Medical Practice: A Code of Conduct for Doctors in Australia states that in caring for patients towards the end of their life, good medical practice involves facilitating advance care planning. OBJECTIVE: This article discusses the role of advance care planning in end-of-life care, with an emphasis on the ethical and legal framework for advance care directives. DISCUSSION: There has been an increased focus on advanced care planning and advance care directives in Australia, partly driven by the ageing population and technological advances, as well as the principle of patient-centred care. General practitioners have an important role in initiating and facilitating advance care planning. PMID- 25114987 TI - Back pain in a cancer patient: a case study. PMID- 25114988 TI - 'Help us, she's fading away': How to manage the patient with anorexia nervosa. AB - BACKGROUND: Although integral to the early detection and treatment of anorexia nervosa, there is a paucity of clear guidance available for general practitioners (GPs). This paper attempts to bridge the gap between the specialist and generalist literature to assist the busy GP feel confident in identifying and managing these patients. OBJECTIVE: On reading this article it is anticipated the GP will feel well equipped to screen for and provide ongoing treatment to patients who pre-sent with eating disorders, particularly anorexia nervosa. This paper provides guidance for the identification and ongoing management of patients with anorexia nervosa, and supporting their carers. DISCUSSION: People affected by eating disorders, particularly anorexia nervosa, may deny having a problem, minimise their symptoms and resist treatment yet engage partially with their GP throughout the course of their illness. There are well-validated, quick screening tools that the non-specialist can use to identify patients at high risk of having an eating disorder. PMID- 25114989 TI - GP pain management: what are the 'Ps' and 'As' of pain management? AB - BACKGROUND: Pain is one common reason for clinical encounters in primary care. The complex nature of chronic pain syndromes can make assessment and management daunting at times. OBJECTIVE: This article presents an easy scheme to help general practitioners efficiently assess, manage and review/follow up patients with chronic pain. DISCUSSION: The mnemonic presented for assessment is the '4Ps' (pain, other pathology/past medical history, performance/function and psychological/psychiatric status). For management, we can also use '4Ps' (physical, psychological, pharmacological and procedural) and for review there are the '6As' (activities, analgesia, adverse effects, aberrance behaviours, affects and adequate documentation). PMID- 25114990 TI - Exercise in pregnancy. AB - BACKGROUND: Exercise is an inconsistently managed area in the health of expectant mothers. It is an area where family doctors have an opportunity to be well informed and willing to give advice. OBJECTIVE: To provide simple advice on safe exercise practice in pregnancy. DISCUSSION: Exercise in pregnancy has multiple benefits for the mother, including reduced risk of mental health problems, diabetes and hypertension, and faster recovery after delivery. There are no proven risks to the fetus if practiced safely. Understanding the physiological changes of pregnancy and the possible complications of high-intensity or contact sport is important but in general, moderate levels of exercise 3-4 times per week is safe for both mother and baby in low-risk pregnancies. PMID- 25114991 TI - Periorbital oedema after dental extraction: a case study. PMID- 25114992 TI - A heavy burden: remaining vigilant with herbal remedies. PMID- 25114993 TI - Ulcerated upper lip tumour: diagnostic procedure. AB - A Mediterranean Spanish woman, aged 56 years and in good health, presented with a nodule above her upper lip, which had rapidly evolved to central ulceration with crusting. As part of the work-up, samples were taken for microbiological and histopathological investigation. At the follow-up appointment the lesion had almost disappeared and a small fibrotic area of scarring remained. The diagnostic procedure to distinguish between localised cutaneous leishmaniasis and keratoacanthoma, both characterised by rapidly growing nodules on the face, is presented in this case-based article. PMID- 25114994 TI - Self-reported access to and quality of healthcare for diabetes: do the severely obese experience equal access? AB - BACKGROUND: Given reported pejorative views that health professionals have about patients who are severely obese, we examined the self-reported views of the quality and availability of diabetes care from the perspective of adults with type 2 diabetes (T2DM), stratified by body mass index (BMI). METHODS: 1795 respondents to the Diabetes MILES - Australia national survey had T2DM. Of these, 530 (30%) were severely obese (BMI >=35 kg/m2) and these participants were matched with 530 controls (BMI <35 kg/m2). Data regarding participants' self reported interactions with health practitioners and services were compared. RESULTS: Over 70% of participants reported that their general practitioner was the professional they relied on most for diabetes care. There were no between group differences in patient-reported availability of health services, quality of interaction with health practitioners, resources and support for self-management, or access to almost all diabetes services. DISCUSSION: Participants who were severely obese did not generally report greater difficulty in accessing diabetes care. PMID- 25114995 TI - Predicting recovery from whiplash injury in the primary care setting. AB - BACKGROUND: The effect of expectation of recovery on the recovery rate of whiplash patients in the primary care setting is not known. METHODS: Whiplash patients were assessed in a primary care setting within 1 week of their collision for their expectations of recovery and were re-examined 3 months later for recovery. RESULTS: Initial expectations of recovery predicted recovery. According to adjusted odds ratios, subjects who expected 'to get better slowly' had a recovery rate that was nearly 1.9 times that of subjects with poor recovery expectations. Subjects who expected 'to get better soon' had a recovery rate that was 2.6 times greater than either of those with poor recovery expectations. DISCUSSION: In the primary care setting, asking patients with whiplash about their expectations of recovery is a useful predictor of their outcome. PMID- 25114996 TI - Outpatient alcohol withdrawal management for Aboriginal and Torres Strait Islander peoples. AB - BACKGROUND: There is concern from within Aboriginal and Torres Strait Islander communities about the lack of access to alcohol withdrawal management ('detox') services. Outpatient detox is described within national Australian guidelines as a safe option for selected drinkers. However, uncertainly exists as to how suited Aboriginal and Torres Strait Islander peoples are to this approach. ? METHODS: Consultations were conducted with stakeholders of four health services providing outpatient detox for Aboriginal and Torres Strait Islander peoples in NSW. Thematic analysis was performed to determine elements perceived as important for success. RESULTS: Key themes that emerged were individual engagement, flexibility, assessment of suitability, Aboriginal staff and community engagement, practical support, counselling, staff education and support, coping with relapse and contingency planning. ? DISCUSSION: There is a need to improve access to alcohol detox services for Aboriginal and Torres Strait Islander peoples. The outpatient setting seems to be a feasible and safe environment to provide this kind of service for selected drinkers. PMID- 25114997 TI - Misoprostol for post-partum haemorrhage in the Australian bush. AB - Obstetric haemorrhage, particularly post-partum haemorrhage has been noted to be the third most common direct cause of maternal deaths. According to the Australian Institute of Health and Welfare (AIHW), bleeding contributed up to 14% of maternal deaths caused by obstetric complications between the years 2003 and 2005. PMID- 25114998 TI - The importance of LPNs. PMID- 25114999 TI - Author's response. PMID- 25115001 TI - WHO and partners launch Ebola response plan. PMID- 25115000 TI - Reply to Lopez et al.: Consumption-based accounting helps mitigate global air pollution. PMID- 25115002 TI - Multiple crises overwhelm emergency food relief agencies. PMID- 25115003 TI - Funding: Wellcome Trust selects sustainable health projects. PMID- 25115004 TI - Jeannie Isabelle Rosoff. PMID- 25115006 TI - Biotechnology of food additives. Preface. PMID- 25115005 TI - Studies of local structural distortions in strained ultrathin BaTiO3 films using scanning transmission electron microscopy. AB - Ultrathin ferroelectric heterostructures (SrTiO3/BaTiO3/BaRuO3/SrRuO3) were studied by scanning transmission electron microscopy (STEM) in terms of structural distortions and atomic displacements. The TiO2-termination at the top interface of the BaTiO3 layer was changed into a BaO-termination by adding an additional BaRuO3 layer. High-angle annular dark-field (HAADF) imaging by aberration-corrected STEM revealed that an artificially introduced BaO termination can be achieved by this interface engineering. By using fast sequential imaging and frame-by-frame drift correction, the effect of the specimen drift was significantly reduced and the signal-to-noise ratio of the HAADF images was improved. Thus, a quantitative analysis of the HAADF images was feasible, and an in-plane and out-of-plane lattice spacing of the BaTiO3 layer of 3.90 and 4.22 A were determined. A 25 pm shift of the Ti columns from the center of the unit cell of BaTiO3 along the c-axis was observed. By spatially resolved electron energy-loss spectroscopy studies, a reduction of the crystal field splitting (CFS, DeltaL3=1.93 eV) and an asymmetric broadening of the eg peak were observed in the BaTiO3 film. These results verify the presence of a ferroelectric polarization in the ultrathin BaTiO3 film. PMID- 25115007 TI - Hellbender genome sequences shed light on genomic expansion at the base of crown salamanders. AB - Among animals, genome sizes range from 20 Mb to 130 Gb, with 380-fold variation across vertebrates. Most of the largest vertebrate genomes are found in salamanders, an amphibian clade of 660 species. Thus, salamanders are an important system for studying causes and consequences of genomic gigantism. Previously, we showed that plethodontid salamander genomes accumulate higher levels of long terminal repeat (LTR) retrotransposons than do other vertebrates, although the evolutionary origins of such sequences remained unexplored. We also showed that some salamanders in the family Plethodontidae have relatively slow rates of DNA loss through small insertions and deletions. Here, we present new data from Cryptobranchus alleganiensis, the hellbender. Cryptobranchus and Plethodontidae span the basal phylogenetic split within salamanders; thus, analyses incorporating these taxa can shed light on the genome of the ancestral crown salamander lineage, which underwent expansion. We show that high levels of LTR retrotransposons likely characterize all crown salamanders, suggesting that disproportionate expansion of this transposable element (TE) class contributed to genomic expansion. Phylogenetic and age distribution analyses of salamander LTR retrotransposons indicate that salamanders' high TE levels reflect persistence and diversification of ancestral TEs rather than horizontal transfer events. Finally, we show that relatively slow DNA loss rates through small indels likely characterize all crown salamanders, suggesting that a decreased DNA loss rate contributed to genomic expansion at the clade's base. Our identification of shared genomic features across phylogenetically distant salamanders is a first step toward identifying the evolutionary processes underlying accumulation and persistence of high levels of repetitive sequence in salamander genomes. PMID- 25115008 TI - Frequent changes in expression profile and accelerated sequence evolution of duplicated imprinted genes in arabidopsis. AB - Eukaryotic genomes have large numbers of duplicated genes that can evolve new functions or expression patterns by changes in coding and regulatory sequences, referred to as neofunctionalization. In flowering plants, some duplicated genes are imprinted in the endosperm, where only one allele is expressed depending on its parental origin. We found that 125 imprinted genes in Arabidopsis arose from gene duplication events during the evolution of the Brassicales. Analyses of 46 gene pairs duplicated by an ancient whole-genome duplication (alpha WGD) indicated that many imprinted genes show an accelerated rate of amino acid changes compared with their paralogs. Analyses of microarray expression data from 63 organ types and developmental stages indicated that many imprinted genes have expression patterns restricted to flowers and/or seeds in contrast to their broadly expressed paralogs. Assays of expression in orthologs from outgroup species revealed that some imprinted genes have acquired an organ-specific expression pattern restricted to flowers and/or seeds. The changes in expression pattern and the accelerated sequence evolution in the imprinted genes suggest that some of them may have undergone neofunctionalization. The imprinted genes MPC, HOMEODOMAIN GLABROUS6 (HDG6), and HDG3 are particularly interesting cases that have different functions from their paralogs. This study indicates that a large number of imprinted genes in Arabidopsis are evolutionarily recent duplicates and that many of them show changes in expression profiles and accelerated sequence evolution. Acquisition of imprinting is a mode of duplicate gene divergence in plants that is more common than previously thought. PMID- 25115009 TI - The effects of microsatellite selection on linked sequence diversity. AB - The genome-wide scan for selection is an important method for identifying loci involved in adaptive evolution. However, theory that underlies standard scans for selection assumes a simple mutation model. In particular, recurrent mutation of the selective target is not considered. Although this assumption is reasonable for single-nucleotide variants (SNVs), a microsatellite targeted by selection will reliably violate this assumption due to high mutation rate. Moreover, the mutation rate of microsatellites is generally high enough to ensure that recurrent mutation is pervasive rather than occasional. It is therefore unclear if positive selection targeting microsatellites can be detected using standard scanning statistics. Examples of functional variation at microsatellites underscore the significance of understanding the genomic effects of microsatellite selection. Here, we investigate the joint effects of selection and complex mutation on linked sequence diversity, comparing simulations of microsatellite selection and SNV-based selective sweeps. We find that selection on microsatellites is generally difficult to detect using popular summaries of the site frequency spectrum, and, under certain conditions, using popular methods such as the integrated haplotype statistic and SweepFinder. However, comparisons of the number of haplotypes (K) and segregating sites (S) often provide considerable power to detect selection on microsatellites. We apply this knowledge to a scan of autosomes in the human CEU population (CEPH population sampled from Utah). In addition to the most commonly reported targets of selection in European populations, we identify numerous novel genomic regions that bear highly anomalous haplotype configurations. Using one of these regions intron 1 of MAGI2-as an example, we show that the anomalous configuration is coincident with a perfect CA repeat of length 22. We conclude that standard genome-wide scans will commonly fail to detect mutationally complex targets of selection but that comparisons of K and S will, in many cases, facilitate their identification. PMID- 25115010 TI - Evolutionary dynamics of the mitochondrial genome in the evaniomorpha (hymenoptera)-a group with an intermediate rate of gene rearrangement. AB - We determined the complete mitochondrial (mt) genomes of three evaniomorph species, Ceraphron sp. (Ceraphronoidea), Gasteruption sp. (Evanioidea), and Orthogonalys pulchella (Trigonalyoidea) as well as the nearly complete mt genome from another evaniomorph species, Megalyra sp. (Megalyroidea). Each of them possesses dramatic gene rearrangements, including protein-coding or rRNA genes. Gene inversions were identified in all of these mt genomes; for example, the two rRNA genes have inverted and moved into the nad2-cox1 junction in the Megalyra sp. mt genome. In addition, we found two copies of a 10-bp complementary repeat at the beginning of rrnS and at the end of trnL(2) in the Gasteruption sp. mt genome, consistent with recombination as the possible mechanism for gene inversion and long-range movement. Although each of the genomes contains a number of repeats of varying size, there was no consistent association of the size or number of repeats with the extent or type of gene rearrangement. The breakpoint distance analysis showed the Evaniomorpha has an intermediate rate of gene rearrangement. Sequence-based phylogenetic analyses of 13 protein-coding and 2 rRNA genes in 22 hymenopteran taxa recovered a paraphyletic Evaniomorpha with the Aculeata nested within it. Within the Evaniomorpha, our analyses confirmed the Trigonalyoidea + Megalyroidea as the sister group to the Aculeata and recovered a novel clade, Ceraphronoidea + Evanioidea. In contrast to previous hymenopteran phylogenetic studies, the internal relationships of the Evaniomorpha were highly supported and robust to the variation of alignment approach and phylogenetic inference approach. PMID- 25115011 TI - Small but powerful, the primary endosymbiont of moss bugs, Candidatus Evansia muelleri, holds a reduced genome with large biosynthetic capabilities. AB - Moss bugs (Coleorrhyncha: Peloridiidae) are members of the order Hemiptera, and like many hemipterans, they have symbiotic associations with intracellular bacteria to fulfill nutritional requirements resulting from their unbalanced diet. The primary endosymbiont of the moss bugs, Candidatus Evansia muelleri, is phylogenetically related to Candidatus Carsonella ruddii and Candidatus Portiera aleyrodidarum, primary endosymbionts of psyllids and whiteflies, respectively. In this work, we report the genome of Candidatus Evansia muelleri Xc1 from Xenophyes cascus, which is the only obligate endosymbiont present in the association. This endosymbiont possesses an extremely reduced genome similar to Carsonella and Portiera. It has crossed the borderline to be considered as an autonomous cell, requiring the support of the insect host for some housekeeping cell functions. Interestingly, in spite of its small genome size, Evansia maintains enriched amino acid (complete or partial pathways for ten essential and six nonessential amino acids) and sulfur metabolisms, probably related to the poor diet of the insect, based on bryophytes, which contains very low levels of nitrogenous and sulfur compounds. Several facts, including the congruence of host (moss bugs, whiteflies, and psyllids) and endosymbiont phylogenies and the retention of the same ribosomal RNA operon during genome reduction in Evansia, Portiera, and Carsonella, suggest the existence of an ancient endosymbiotic Halomonadaceae clade associated with Hemiptera. Three possible scenarios for the origin of these three primary endosymbiont genera are proposed and discussed. PMID- 25115013 TI - Author response. PMID- 25115014 TI - Retraction. "Haemodynamic derangement in human immunodeficiency virus-infected patients with hepatitis C virus-related cirrhosis: the role of bacterial translocation". PMID- 25115012 TI - The molecular evolution of the Qo motif. AB - Quinol oxidation in the catalytic quinol oxidation site (Q(o) site) of cytochrome (cyt) bc(1) complexes is the key step of the Q cycle mechanism, which laid the ground for Mitchell's chemiosmotic theory of energy conversion. Bifurcated electron transfer upon quinol oxidation enables proton uptake and release on opposite membrane sides, thus generating a proton gradient that fuels ATP synthesis in cellular respiration and photosynthesis. The Q(o) site architecture formed by cyt b and Rieske iron-sulfur protein (ISP) impedes harmful bypass reactions. Catalytic importance is assigned to four residues of cyt b formerly described as PEWY motif in the context of mitochondrial complexes, which we now denominate Q(o) motif as comprehensive evolutionary sequence analysis of cyt b shows substantial natural variance of the motif with phylogenetically specific patterns. In particular, the Q(o) motif is identified as PEWY in mitochondria, alpha- and epsilon-Proteobacteria, Aquificae, Chlorobi, Cyanobacteria, and chloroplasts. PDWY is present in Gram-positive bacteria, Deinococcus-Thermus and haloarchaea, and PVWY in beta- and gamma-Proteobacteria. PPWF only exists in Archaea. Distinct patterns for acidophilic organisms indicate environment specific adaptations. Importantly, the presence of PDWY and PEWY is correlated with the redox potential of Rieske ISP and quinone species. We propose that during evolution from low to high potential electron-transfer systems in the emerging oxygenic atmosphere, cyt bc(1) complexes with PEWY as Q(o) motif prevailed to efficiently use high potential ubiquinone as substrate, whereas cyt b with PDWY operate best with low potential Rieske ISP and menaquinone, with the latter being the likely composition of the ancestral cyt bc(1) complex. PMID- 25115015 TI - Chronic ulceration of tongue. Histoplasmosis. PMID- 25115016 TI - Newborn skin care guidelines, third edition. PMID- 25115018 TI - Mentoring: have you thought of a formal program? PMID- 25115019 TI - PED virus reinfecting U.S. herds. Virus estimated to have killed 7 million-plus pigs. PMID- 25115020 TI - Agreement will reduce access to some rodenticides. PMID- 25115021 TI - Help line getting more calls about bromethalin. PMID- 25115022 TI - Editorial. PMID- 25115023 TI - SENTIERI Project: Introduction. PMID- 25115024 TI - [Psychopathological mechanisms of childhood trauma]. PMID- 25115025 TI - [What is the present appropriate treatment for renal denervation hypertension?]. PMID- 25115026 TI - [Heat and criticism of mothers and behavioral problems in children with ADHD]. PMID- 25115027 TI - Findings of research misconduct. PMID- 25115028 TI - Findings of research misconduct. PMID- 25115030 TI - Findings of Research Misconduct. PMID- 25115029 TI - Findings of research misconduct. PMID- 25115031 TI - Long-term and trans-generational effects of neonatal experience on sheep behaviour. AB - Early life experiences can have profound long-term, and sometimes transgenerational, effects on individual phenotypes. However, there is a relative paucity of knowledge about effects on pain sensitivity, even though these may impact on an individual's health and welfare, particularly in farm animals exposed to painful husbandry procedures. Here, we tested in sheep whether neonatal painful and non-painful challenges can alter pain sensitivity in adult life, and also in the next generation. Ewes exposed to tail-docking or a simulated mild infection (lipopolysaccharide (LPS)) on days 3-4 of life showed higher levels of pain-related behaviour when giving birth as adults compared with control animals. LPS-treated ewes also gave birth to lambs who showed decreased pain sensitivity in standardized tests during days 2-3 of life. Our results demonstrate long-term and trans-generational effects of neonatal experience on pain responses in a commercially important species and suggest that variations in early life management can have important implications for animal health and welfare. PMID- 25115032 TI - Ectomycorrhizal fungi and past high CO2 atmospheres enhance mineral weathering through increased below-ground carbon-energy fluxes. AB - Field studies indicate an intensification of mineral weathering with advancement from arbuscular mycorrhizal (AM) to later-evolving ectomycorrhizal (EM) fungal partners of gymnosperm and angiosperm trees. We test the hypothesis that this intensification is driven by increasing photosynthate carbon allocation to mycorrhizal mycelial networks using 14CO2-tracer experiments with representative tree-fungus mycorrhizal partnerships. Trees were grown in either a simulated past CO2 atmosphere (1500 ppm)-under which EM fungi evolved-or near-current CO2 (450 ppm). We report a direct linkage between photosynthate-energy fluxes from trees to EM and AM mycorrhizal mycelium and rates of calcium silicate weathering. Calcium dissolution rates halved for both AM and EM trees as CO2 fell from 1500 to 450 ppm, but silicate weathering by AM trees at high CO2 approached rates for EM trees at near-current CO2. Our findings provide mechanistic insights into the involvement of EM-associating forest trees in strengthening biological feedbacks on the geochemical carbon cycle that regulate atmospheric CO2 over millions of years. PMID- 25115033 TI - Rodents of the Caribbean: origin and diversification of hutias unravelled by next generation museomics. AB - The Capromyidae (hutias) are endemic rodents of the Caribbean and represent a model of dispersal for non-flying mammals in the Greater Antilles. This family has experienced severe extinctions during the Holocene and its phylogenetic affinities with respect to other caviomorph relatives are still debated as morphological and molecular data disagree. We used target enrichment and next generation sequencing of mitochondrial and nuclear genes to infer the phylogenetic relationships of hutias, estimate their divergence ages, and understand their mode of dispersal in the Greater Antilles.We found that Capromyidae are nested within Echimyidae (spiny rats) and should be considered a subfamily thereof. We estimated that the split between hutias and Atlantic Forest spiny rats occurred 16.5 (14.8-18.2) million years ago (Ma), which is more recent than the GAARlandia land bridge hypothesis (34-35 Ma). This would suggest that during the Early Miocene, an echimyid-like ancestor colonized the Greater Antilles from an eastern South American source population via rafting. The basal divergence of the Hispaniolan Plagiodontia provides further support for a vicariant separation between Hispaniolan and western islands (Bahamas, Cuba, Jamaica) hutias. Recent divergences among these western hutias suggest Plio Pleistocene dispersal waves associated with glacial cycles. PMID- 25115034 TI - Implementing the Affordable Care Act: state action on quality improvement in state-based marketplaces. AB - Under the Affordable Care Act, the health insurance marketplaces can encourage improvements in health care quality by: allowing consumers to compare plans based on quality and value, setting common quality improvement requirements for qualified health plans, and collecting quality and cost data to inform improvements. This issue brief reviews actions taken by state-based marketplaces to improve health care quality in three areas: 1) using selective contracting to drive quality and delivery system reforms; 2) informing consumers about plan quality; and 3) collecting data to inform quality improvement. Thirteen state based marketplaces took action to promote quality improvement and delivery system reforms through their marketplaces in 2014. Although technical and operational challenges remain, marketplaces have the potential to drive systemwide changes in health care delivery. PMID- 25115035 TI - Caring for high-need, high-cost patients: what makes for a successful care management program? AB - Provider groups taking on risk for the overall costs of care in accountable care organizations are developing care management programs to improve care and thereby control costs. Many such programs target "high-need, high-cost" patients: those with multiple or complex conditions, often combined with behavioral health problems or socioeconomic challenges. In this study we compared the operational approaches of 18 successful complex care management programs in order to offer guidance to providers, payers, and policymakers on best practices for complex care management. We found that effective programs customize their approach to their local contexts and caseloads; use a combination of qualitative and quantitative methods to identify patients; consider care coordination one of their key roles; focus on building trusting relationships with patients as well as their primary care providers; match team composition and interventions to patient needs; offer specialized training for team members; and use technology to bolster their efforts. PMID- 25115036 TI - A review of avian probiotics. AB - Probiotics have been used in poultry for decades and have become common in the pet bird industry. Desirable characteristics of probiotic organisms are that they are nonpathogenic, have the ability to adhere to intestinal epithelial cells, have the ability to colonize and reproduce in the host, have the ability to be host-specific, survive transit through the gastrointestinal tract and exposure to stomach acid and bile, produce metabolites that inhibit or kill pathogenic bacteria, modulate gastrointestinal immune responses, and survive processing and storage. Purported benefits in birds are disease prevention and promotion of growth. Recommendations for use in avian species are for periodic use to replenish normal flora, use after antibiotic therapy to reestablish normal flora, and use during periods of stress to counter effects of immunosuppression. PMID- 25115037 TI - Pharmacokinetics of single oral dose of pimobendan in Hispaniolan Amazon parrots (Amazona ventralis). AB - Pimobendan is a phosphodiesterase (PDE) inhibitor and calcium sensitizer with inotropic, lusitropic, and rasodilator properties used in the treatment of congestive heart failure. The mechanism of action is by inhibition of PDE III and V and by increasing intracellular calcium sensitivity in the cardiac myocardium. Pharmacokinetic and pharmacodynamic studies have been published in humans, dogs, and cats, but there are no studies in avian species. Pimobendan has been used in birds at the empirical dosage of 0.25 mg/kg q12h. To determine the pharmacokinetic parameters of pimobendan in Hispaniolan Amazon parrots (Amazona ventralis), 3 pilot studies with 2 birds, each receiving 1, 3, and 10 mg/kg PO, provided the basis for the pivotal trials with 6 birds, each receiving 10 mg/kg PO using 2 different suspensions. Blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 18 hours after drug administration. Plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (HPLC/MS) by use of electrospray ionization. Because of the erratic and low concentrations of pimobendan, pharmacokinetic parameters were calculated using naive averaged analysis. Plasma concentrations after commercial pimobendan tablet suspension at 10 mg/kg reached a Cmax of 8.26 ng/mL at 3 hours with a terminal half-life of 2.1 hours, while concentrations after the bulk chemical suspension reached a Cmax of 1.28 ng/mL at 12 hours and had a terminal half-life of 2.3 hours. Further studies evaluating the effect of oral pimobendan in parrots are needed. PMID- 25115038 TI - Inhibition of the reproductive system by deslorelin in male and female pigeons (Columba livia). AB - Veterinary practitioners frequently encounter disorders of the reproductive system in avian patients. Management of these disorders relies on manipulating reproduction by modifying the environment, diet, and social interactions, and by the use of pharmacologic agents and surgery, with varying levels of success and side effects. An alternative is to use the gonadotropin-releasing hormone (GnRH) agonist deslorelin to suppress the pituitary-gonadal axis. To determine the efficacy of deslorelin in domestic pigeons (Columba livia), male (n = 10) and female (n = 10) birds each were implanted intramuscularly with a single long acting implant containing 4.7 mg deslorelin. Untreated males (n = 11) and females (n = 10) were used as controls. The baseline serum concentration of luteinizing hormone (LH) was assayed at 7, 28, 56, and 84 days after treatment, and egg production was recorded weekly. In females, deslorelin administration significantly reduced serum LH concentrations compared to pretreatment levels at 7, 28, 56, and 84 days (P < .05). In males, deslorelin significantly reduced LH concentrations at 7, 28, and 56 days (P < .05). Female birds treated with deslorelin laid significantly fewer eggs over the course of the study (mean = 1.46, SEM = 0.84) compared with controls (mean = 5.54, SEM = 0.88). Deslorelin treatment had no discernible effect on body weight. Deslorelin is effective for controlling egg laying in female pigeons for at least 49 days, but further research is required to determine the effects on male fertility and the duration of action in both sexes. PMID- 25115040 TI - Reference intervals, longitudinal analyses, and index of individuality of commonly measured laboratory variables in captive bald eagles (Haliaeetus leucocephalus). AB - The objectives of this study were to determine reference intervals, perform longitudinal analyses, and determine the index of individuality (IoI) of 8 hematologic, and 13 biochemical and electrophoretic variables for a group of captive bald eagles (Haliaeetus leucocephalus). Reference intervals were determined from blood samples collected during annual wellness examinations for 41 eagles (23 male and 18 female) with ages ranging between 6 and 43 years (18.7 +/- 7.4, mean +/- SD) at the time of sample collection. Longitudinal analyses and IoI were determined for measured hematologic, biochemical, and protein electrophoretic variables, both individually and as a group, for a subset of 16 eagles (10 male and 6 female) during a 12-year period. This smaller group of eagles ranged in age between 2 and 20 years at the start of the study period, and between 14 and 32 years (21.9 +/- 5.0, mean +/- SD) at the end of the study period. Significant increases with age within the group of 16 eagles were observed only for red blood cells, percent heterophils, total protein, and beta globulin protein fraction, while albumin:globulin decreased significantly with age. A low IoI (> or = 1.4) was determined for all hematologic and biochemical variables except gamma globulins, which had high IoI (< or = 0.6) for 3 individuals within the subset of 16. PMID- 25115039 TI - Nonmedical factors associated with feather picking in pet psittacine birds. AB - A nested case-control study was performed to determine nonmedical risk factors associated with feather picking in psittacine birds. Forty-two case birds, reported by their owners to pick their feathers, and 126 unaffected birds were compared. The odds of feather picking were higher in 2 species categories, African grey parrots (Psitticus erithacus, adjusted odds ratio [ORadj = 8.4, P < .001) and cockatoos (Cacatua species, ORadj = 12.7, P < .001). The odds of feather picking also were higher for birds that were out of their cages more than 8 hours per day (ORadj = 7.4, P < .001) and for birds that had been taken in by the owner as a "rescue" (ORadj = 4.7, P < .01). The odds of feather picking decreased by almost 90% (ORadj = 0.1, P < .005) for birds that interacted with people at least 4 hours a day. These findings identify characteristics that practitioners may want to include when asking bird owners about behavioral history and may be useful in focusing future research regarding this behavior. PMID- 25115041 TI - American kestrel (Falco spaverius) fledgling with severe bilateral periorbital swelling and infection with Mycoplasma buteonis, Avibacterium (Pasteurella) gallinarum, and Staphylococcus pasteuri. AB - Abstract: A female American kestrel (Falco spaverius) fledgling was found on the ground with a suspected trauma to the right eye and open-mouth breathing. During the first 2 days of hospitalization, the bird developed severe bilateral periorbital cellulitis, blepharoedema, and sinusitis. The periocular tissues of the right globe were devitalized and communicated with a fistula at the commissure of the right side of the beak. The blepharoedema of the left eye was aspirated and yielded a dark colored malodorous fluid, which was submitted for aerobic bacterial and Mycoplasma cultures. Results showed a mixed infection with Mycoplasma buteonis, Avibacterium gallinarum, and Staphylococcus pasteuri, all of which are not commonly isolated from birds of prey. With antimicrobial therapy, supportive care, and surgical debridement of the right periocular necrotic tissues and adhesed phthisical globe, the kestrel recovered from this severe mixed upper respiratory infection. PMID- 25115042 TI - Central vestibular disease in a blue and gold macaw (Ara ararauna) with cerebral infarction and hemorrhage. AB - A 24-year-old female blue and gold macaw (Ara ararauna) was presented for an acute onset of left head tilt. On examination, the macaw was dehydrated and had a 120-degree left head tilt, decreased proprioception of the left pelvic limb, and intermittent vertical nystagmus. Results of hematologic testing and biochemical analysis revealed severe leukocytosis with lymphopenia and heterophilia and a high uric acid concentration. Radiographs showed bilateral intertarsal joint osteoarthritis and a healed ulnar fracture. Magnetic resonance imaging of the brain revealed focal T2 and fluid-attenuated inversion recovery hyperintense lesions in the right cerebral hemisphere and in the midbrain. The midbrain lesion showed susceptibility artifact on the T2* sequence, suggesting hemorrhage. In the T2* sequence, iron accumulation (as seen with hemorrhage) distorts the magnetic signal, resulting in the production of a susceptibility artifact, which can then be visualized as a region of hypointensity. The bird was hospitalized but died despite intensive care. Necropsy revealed multiple cerebral vascular lesions including an acute cerebral infarct, a ruptured midbrain aneurysm, and multifocal systemic atherosclerosis. To our knowledge, this is the first report of a cerebral aneurysm in a bird. This report correlates the clinical presentation, imaging, and histopathologic findings in a macaw with central vestibular disease and demonstrates how advanced imaging techniques can identify hemorrhagic lesions through the T2* sequence. PMID- 25115044 TI - The "original" AAV: the founding of the Association of Avian Veterinarians. PMID- 25115043 TI - Nasal adenocarcinoma and secondary chronic sinusitis in a hyacinth macaw (Anodorhynchus hyacinthinus). AB - An adult male hyacinth macaw (Anodorhynchus hyacinthinus) that presented for acute onset nasal discharge and dyspnea had purulent discharge from the right naris and serosanguineous discharge from the left naris on physical examination. Results of a complete blood count revealed severe leukocytosis with a mature heterophilia. Computed tomography scans showed a large amount of soft-tissue attenuating material within the infraorbital sinus and associated diverticula. Aerobic culture results of the nasal discharge showed a mixed population of Staphylococcus intermedius and Pasteurella species, including Pasteurella pneumotropica; all isolated bacteria were susceptible to enrofloxacin. Clinical signs did not resolve over the course of 9 weeks of antibiotic treatment. The macaw died after cardiopulmonary arrest while hospitalized. At necropsy, a 2 x 2 x 3-cm firm, tan, friable, space-occupying mass surrounded by a thick exudate was present in the left preorbital diverticulum of the infraorbital sinus. The cranioventral one-third of the trachea contained a 4 x 0.5-cm white-yellow plaque. On histologic examination, the sinus mass was diagnosed as a nasal adenocarcinoma, and the tracheal plaque was caused by fungal infection, most likely with an Aspergillus species. PMID- 25115046 TI - New veterinary graduates: spreading their wings and exploring career paths in avian and exotic animal medicine. PMID- 25115045 TI - Tracking migrations of yellow-billed loons (Gavia adamsii) from the Canadian arctic. AB - Because the population of yellow-billed loons (Gavia adamsii) is declining, satellite telemetry was used to learn more about the needs of this species and the interdependencies of various populations that breed in isolated regions. In July 2013, the author accompanied a team of biologists to Victoria Island in the Canadian Arctic to surgically implant satellite transmitters in 14 yellow-billed loons. This article chronicles the trip with the objective of connecting the reader with the loons and the interesting people that strive to conserve them. PMID- 25115047 TI - Rectal adenocarcinoma. PMID- 25115048 TI - Measuring and reporting service efficiency and effectiveness. PMID- 25115049 TI - Universal Health Coverage Scheme impact on well-being in rural Thailand. AB - PURPOSE: The purpose of this paper is to investigate the extent to which the Thai Universal Healthcare Insurance Coverage Scheme (UC) has contributed to villagers' well-being in the northeast of Thailand. Public opinion polls specifically advocate the schemes are used to justify its ongoing political support. However, the question still remains as to whether it has made a difference in the lives of poorer rural people. DESIGN/METHODOLOGY/APPROACH: A multi-methods approach and a well-being focused evaluation (WFE) approach are used to understand villagers' experiences of having and using the scheme and investigate the villagers' satisfaction with the scheme and how this satisfaction has contributed to their life as a whole. FINDINGS: It is found that the scheme had made a valuable contribution to improving perceived wellbeing amongst villagers. Apart from the direct benefits of having that healthcare when needed, there is also the indirect benefit of increasing villagers' sense of security that healthcare will be accessible if required. RESEARCH LIMITATIONS/IMPLICATIONS: There are still pertinent issues for policy consideration; for example, almost 31 per cent of the villagers with the card have never used it. Approximately 22 per cent of people using the card reported dissatisfactions. Although healthcare direct-costs were now more affordable, a range of opportunity costs, geographic, social, cultural and other factors still need to be factored into further policy and service development to make the scheme more equitable and effective. ORIGINALITY/VALUE: The study proposes "WFE", a new evaluation approach. WFE may also be applied to other forms of social policy particularly concerning the impact of its policy on people's well-being. PMID- 25115050 TI - Differences in quality of life between pediatric sickle cell patients who used hydroxyurea and those who did not. AB - PURPOSE: The purpose of this paper is to examine the differences in quality of life (QoL) between two groups of pediatric sickle cell patients: those who used hydroxyurea and those who chose not to use the medication to treat sickle cell disease. DESIGN/METHODOLOGY/APPROACH: The study was a quantitative, non randomized, cross-sectional, comparative study. In total, 100 children ages seven to 17 participated in the study. Parents of the patients completed a demographic questionnaire while the participants completed the Pediatric Quality of Life Inventory (Peds QoL) and Sickle Cell Disease Quality of Life Inventory (SCD QoL). FINDINGS: The Ped QoL regression analysis revealed that hydroxyurea use and parental marital status accounted for a significant proportion of the variance in Ped QoL. The SCD QoL regression analysis also revealed that hydroxyurea and age accounted for a significant proportion of the variance in SCD QoL. Finally, the regression analysis revealed that SCD, parental marital status, parental income, sex, age, race and number of siblings did not account for a significant proportion of the variance in SCD crises per year. ORIGINALITY/VALUE: This paper proved a need to study the differences in QoL between those pediatric patients who used hydroxyurea and those who did not use the medication. PMID- 25115051 TI - Illusion or delusion--Lean management in the health sector. AB - PURPOSE: There has been considerable interest in the implementation of practices imported from manufacturing into healthcare as a solution to rising healthcare spending and disappointing patient safety indicators. One approach that has attracted particular interest is Lean management and the purpose of this paper is to engage with this topic. DESIGN/METHODOLOGY/APPROACH: Secondary research. FINDINGS: Despite widespread enthusiasm about the potential of Lean management processes, evidence about its contribution to higher organisational performance remains inconsistent. RESEARCH LIMITATIONS/IMPLICATIONS: This paper engages with the major Lean concepts of operations management and human resource management, including just-in-time, total quality management, total productive maintenance and does not engage in-depth with concepts related to employee empowerment, and training PRACTICAL IMPLICATIONS: This paper contributes to the organisational management literature in healthcare by showing that although Lean management seems to have the potential to improve organisational performance it is far from a panacea against under performing hospitals. SOCIAL IMPLICATIONS: It informs policy making by suggesting that a progressive managerial philosophy has a stronger impact on healthcare performance than the adoption of practices from any particular managerial approach. ORIGINALITY/VALUE: This paper provides a critical evaluation of the impact of Lean practices in informing healthcare policy. The paper contributes to the organisational management literature in healthcare by showing that even though Lean management in healthcare appears to have the potential to improve organisational performance; there remain problems with its application. PMID- 25115052 TI - An integrated approach for prioritized process improvement. AB - PURPOSE: The purpose of this paper is to propose an integrated framework to simultaneously identify and improve healthcare processes that are important from the healthcare provider's and patient's perspectives. DESIGN/METHODOLOGY/APPROACH: A modified quality function deployment (QFD) chart is introduced to the field of healthcare quality assurance. A healthcare service example is used to demonstrate the utility of the proposed chart. FINDINGS: The proposed framework is versatile and can be used in a wide variety of healthcare quality improvement contexts, wherein, two different perspectives are needed to be considered for identifying and improving critical healthcare processes. PRACTICAL IMPLICATIONS: The modified QFD chart used in conjunction with the stacked Pareto chart will facilitate the identification of key performance metrics from the patient's and the hospital's perspectives. Subsequently, the chief contributory factors at different levels are identified in a very efficient manner. ORIGINALITY/VALUE: Healthcare quality improvement professionals will be able to use the proposed modified QFD chart in association with stacked Pareto chart for effective quality assurance. PMID- 25115053 TI - Regulating healthcare complaints: a literature review. AB - PURPOSE: The purpose of this paper is to explore approaches to the regulation of healthcare complaints and disciplinary processes. DESIGN/METHODOLOGY/APPROACH: A literature review was conducted across Medline, Sociological Abstracts, Web of Science, Google Scholar and the health, law and social sciences collections of Informit, using terms tapping both the complaints process and regulation generally. FINDINGS: A total of 118 papers dealing with regulation of health complaints or disciplinary proceedings were located. The review reveals a shift away from self-regulation towards greater external oversight, including innovative regulatory approaches including "networked governance and flexible or "responsive" regulation. It reports growing interest in adoption of strategic and responsive approaches to health complaints governance, by rejecting traditional legal forms in favor of more strategic and responsive forms, taking account of the complexity of adverse health events by tailoring responses to individual circumstances of complainants and their local environments. ORIGINALITY/VALUE: The challenge of how to collect and harness complaints data to improve the quality of healthcare at a systemic level warrants further research. Scope also exists for researching health complaints commissions and other "meta-regulatory" bodies to explore how to make these processes fairer and better able to meet the complex needs of complainants, health professionals, health services and society. PMID- 25115054 TI - College clinic service quality and patient satisfaction. AB - PURPOSE: The purpose of this paper is to identify the service quality dimensions that play an important role in patient satisfaction in campus clinics in Delhi; assess student satisfaction with service; and suggests ways to improve areas of dissatisfaction. DESIGN/METHODOLOGY/APPROACH: A questionnaire was distributed to students who had completed at least two consultations at the college clinic. Convenience sampling was used to approach respondents. The questionnaire uses modified SERVQUAL and other instruments, including original dimensions and those constructed through detailed discussions. Factor analyses, reliability tests and the Kaiser-Meyer-Olkin measure of sampling adequacy were conducted. The final sample had a total of 445 respondents. FINDINGS: After factor analysis, the authors found that the dimensions affecting patient satisfaction are: staff professionalism; clinic staff reliability; clinic accessibility and basic facilities; tangibles; cleanliness; awareness of the clinic/diseases and how clinic staff deals with emergencies. Most students were satisfied with the professionalism of the clinic staff. More than 70 percent of the respondents reported that the clinic staff paid good attention to them. The campus clinic was deemed reliable by more than 50 percent of respondents. The students found the clinic's location convenient, with more than 50 percent supporting its location. However, there was dissatisfaction among the students regarding the tangibles of the clinic, with more than 50 percent favoring upgrading. There was satisfaction among the respondents regarding the availability of the doctor after clinic hours, but contact details for the clinic staff were not easily accessible on campus. More than 60 percent of respondents were satisfied with the cleanliness of the campus clinic. More than 50 percent felt that the campus clinic was not equipped to deal with emergencies efficiently. At the same time, 90 percent of respondents reported the availability of referral facilities in case of emergencies. ORIGINALITY/VALUE: The authors believe that this is the first study conducted to assess patient satisfaction in the campus clinics of engineering institutes in Delhi region. This paper provides valuable information to college clinic administrators. PMID- 25115055 TI - Medical record-keeping and patient perception of hospital care quality. AB - PURPOSE: Medical record represents the main information support used by healthcare providers. The purpose of this paper is to examine whether patient perception of hospital care quality related to compliance with medical-record keeping. DESIGN/METHODOLOGY/APPROACH: The authors merged the original data collected as part of a nationwide audit of medical records with overall and subscale perception scores (range 0-100, with higher scores denoting better rating) computed for 191 respondents to a cross-sectional survey of patients discharged from a university hospital. FINDINGS: The median overall patient perception score was 77 (25th-75th percentiles, 68-87) and differed according to the presence of discharge summary completed within eight days of discharge (81 v. 75, p = 0.03 after adjusting for baseline patient and hospital stay characteristics). No independent associations were found between patient perception scores and the documentation of pain assessment and nutritional disorder screening. Yet, medical record-keeping quality was independently associated with higher patient perception scores for the nurses' interpersonal and technical skills component. RESEARCH LIMITATIONS/IMPLICATIONS: First, this was a single-center study conducted in a large full-teaching hospital and the findings may not apply to other facilities. Second, the analysis might be underpowered to detect small but clinically significant differences in patient perception scores according to compliance with recording standards. Third, the authors could not investigate whether electronic medical record contributed to better compliance with recording standards and eventually higher patient perception scores. PRACTICAL IMPLICATIONS: Because of the potential consequences of poor recording for patient safety, further efforts are warranted to improve the accuracy and completeness of documentation in medical records. ORIGINALITY/VALUE: A modest relationship exists between the quality of medical record keeping and patient perception of hospital care. PMID- 25115056 TI - Essentials of total quality management: a meta-analysis. AB - PURPOSE: The purpose of this paper is to identify critical successful factors for Total Quality Management (TQM) implementation. DESIGN/METHODOLOGY/APPROACH: A literature review was conducted to explore the critical successful factors for TQM implementation between 1980 and 2010. FINDINGS: A successful TQM implementation need sufficient education and training, supportive leadership, consistent support of top management, customer focus, employee involvement, process management and continuous improvement of processes. RESEARCH LIMITATIONS/IMPLICATIONS: The review was limited to articles written in English language during the past 30 years. PRACTICAL IMPLICATIONS: From a practical point of view, the findings of this paper provide managers with a practical understanding of the factors that are likely to facilitate TQM implementation in organisations. ORIGINALITY/VALUE: Understanding the factors that are likely to promote TQM implementation would enable managers to develop more effective strategies that will enhance the chances of achieving business excellence. PMID- 25115057 TI - The role of toll-like receptor agonists in the immunotherapy of leishmaniosis. An update and proposal for a new form of anti-leishmanial therapy. AB - The use of toll-like receptor agonists in immunotherapy is a new approach in the prevention of immunosuppression during fatal Leishmania parasite infection. The objective of such immunotherapy is to activate specific cell-mediated immune responses, macrophage activation and antigen-responsive inflammation, to kill intracellular amastigotes. Toll-like receptor agonist-based treatment in immunocompetent hosts can be effective either by selective use of the agonists alone or in combination with the anti-leishmanial drug stibanate. Recent investigations suggest that toll-like receptor signal pathways constitute a possible new mode of anti-leishmanial treatment. This article describes the prospect of toll-like receptor - mediated signal pathways in the immunotherapy of cutaneous and visceral leishmaniosis, as well as post kala-azar dermal leishmaniosis (PKADL), a skin-sequel of visceral infection. Suitable synthetic agonists need to be developed for toll-like receptors to overcome immunosuppression. PMID- 25115058 TI - Toxoplasma gondii and the host cells. AB - The protozoan Toxoplasma gondii, described by Nicolle and Manceaux in 1908, is a ubiquitous and cosmopolitan parasite that infects a wide range of mammal and bird species with high prevalence. The biological success of T. gondii is associated with the formation of a specific relationship between the parasite and host cells leading to the establishment of a latent, chronic infection. During primary infection, acquired mostly by the oral route, the quickly multiplying tachyzoites disseminate through the body crossing several structural-functional barriers as blood-brain or blood-retina, then they transform into dormant bradyzoites which, enclosed in tissue cysts, occupy preferentially the brain, skeletal muscle and eye. Although T. gondii is able to infect all kinds of nucleated cells, it uses strictly defined host cells, dependent on the life-cycle phase and infection stage. The article discusses selected aspects of the parasite passing via the host body barriers as well as particular role of dendritic cells and skeletal muscle cells, used by the parasite as an very effective vehicle to disseminate throughout the host body or the site of long-term T. gondii persistence, respectively. PMID- 25115059 TI - Hirudotherapy in veterinary medicine. AB - The saliva of medicinal leeches, e.g., Hirudo medicinalis and Hirudo verbana commonly used in hirudotherapy, contains more than 100 bioactive substances with various therapeutic effects, including anticoagulant, vasodilator, thrombolytic, anti-inflammatory and anaesthetic properties. Recently, leeches have been used very successfully in veterinary medicine to treat many diseases of animals, especially dogs, cats and horses. The most common indications for the use of leeches are hip and elbow dysplasia, acute and chronic arthritis, diseases associated with inflammation of tendons, ligaments, and fascia, diseases of the vertebrae and the treatment of scars. Leech therapy is a painless procedure which takes an average of 30 to 120 minutes, the time being dependent on the size of the animal. All leeches used in medical procedures should originate only from certified biofarms. The maintenance of sterile conditions for the culture, transport and storage of medical leeches is very important to protect animals from microbial infections. Hirudotherapy is successfully used in veterinary medicine, especially when traditional treatment is not effective, the effects of treatment are too slow, or after surgery, when the tissues may be threatened by venous congestion. PMID- 25115060 TI - Occurrence of coccidia infection in pigeons in amateur husbandry. Diagnosis and prevention. AB - Coccidiosis caused by Eimeria spp. is a common parasitic disease posing a serious problem in pigeon keeping. The aim of the study was to determine the species composition, the degree of coccidia infection and the effect of the coccidiostat used in the course of the disease in two pigeon lofts located in the West Pomerania province. The material for the study came from 180 birds. A total of 330 faecal samples were investigated with two methods: Willis-Schlaafs (qualitative) and McMaster's (quantitative). The pigeons were given the Baycox (Bayer) coccidiostat with toltrazuril as an active substance. The medicament was administered for two days at a dose of 20 mg/kg body weight at three-day intervals. Three species of protozoa were isolated: Eimeria labbeana, E. columbarum, E. columbae, and the infections were mixed. The occurrence of E. labbeana was most commonly reported, which was shown, depending on the pigeon loft and the age of the birds, in 89-93% of young pigeons and in 63-55% of adults. The species E. columbarum and E. columbae were found less frequently. Baycox coccidiostat proved to be highly effective against coccidiosis in pigeons and may also be used in prophylaxis. PMID- 25115062 TI - Chigger mites (Actinotrichida: Parasitengona, Trombiculidae) of Poland. An updated distribution and hosts. AB - The existing body of knowledge regarding the Trombiculidae of Poland is summarized and supplemented with the results of our recent studies. Although around 3000 nominal species are known worldwide, only 18 have been recorded in Poland. Due to the medical and veterinary importance of parasitic larvae, and the complex life cycle which presents difficulties in finding habitats occupied by postlarval forms, most species have been described exclusively from their larvae. This review provides updated information on the host spectrum and distribution of all the trombiculid species hitherto recorded in Poland, supplemented with data on their general distribution and biology. PMID- 25115061 TI - Study on the occurrence of tick-borne encephalitis virus RNA in European bison (Bison bonasus) eliminated at Bialowieza Primeval Forest (north-eastern Poland) in 2005-2009. AB - Tick-borne encephalitis virus (TBEV) (Flaviviridae, Flavivirus) is an arthropod borne virus, an etiologic agent of tick-borne encephalitis (TBE), an infection involving the central nervous system. The disease is endemic in a large region in Eurasia where it is transmitted mainly by Ixodes ricinus in Europe and I. persulcatus ticks in Asia. This is the most important tick-transmitted arbovirus of human pathogenicity in Europe. The Bialowieza Primeval Forest is a well-known endemic focus of tick-borne encephalitis. The aim of this study was to identify the prevalence of tickborne encephalitis virus (TBEV) in European bison, the important hosts of ticks in the Bialowieza Primeval Forest. In the years 2005 2009, 95 blood samples were collected from European bison and examined for the presence of TBEV using nRT-PCR method. No positive results were obtained. For better understanding of TBEV vertebrate reservoir hosts in Poland, further investigations are needed. PMID- 25115063 TI - A comparison of FLOTAC and CFF techniques in detecting gastrointestinal parasites in water buffaloes (Bubalus bubalis). AB - The objective of the study was to compare the usefulness of FLOTAC and centrifugal fecal flotation (CFF) techniques. More specifically, the taxonomic classes (Nematoda and Cestoda) of endoparasites present in fecal samples of buffaloes are identified, the sensitivity and specificity of FLOTAC relative to CFF are calculated, and the agreement of both techniques is evaluated using Kappa statistics. Fresh fecal samples from 220 buffaloes in 10 municipalities were collected. Sheather's sugar was used as a flotation solution for both the FLOTAC and CFF techniques. Of the 220 animals, 109 samples were nematode positive and 111 samples were nematode negative according to the FLOTAC technique, while 74 were found to be positive and 146 negative according to the CFF technique. No cestodes were detected by either technique. The calculated sensitivity for FLOTAC is 89.19% and its specificity is 70.55%. Kappa statistics revealed moderate agreement (k = 0.535) between the two techniques in detecting nematodes. The prevalence observed based on FLOTAC and CFF test were 49.54% (109/220; 95% CI: 47.75-56.34) and 33.64% (72/220; 95% CI: 27.42-40.3), respectively. PMID- 25115065 TI - Professor James Harlan Steele, DVM (1913-2013). Obituary. PMID- 25115064 TI - Histopathological diagnosis in parasitic diseases. AB - Histopathological research is very important in diagnosing human and animal diseases. Detection of histopathological changes during certain parasitic invasions is particularly important for differential diagnosis and often confirms the presence of parasitic diseases. Such studies allow also to conclude on the primary cause of the disease. PMID- 25115067 TI - Improved synthesis of (+/-)-trichodiene--a volatile marker for trichothecene mycotoxins. AB - Trichodiene is the first and only volatile intermediate in the biosynthesis of Fusarium mycotoxins and its detection in the gas-phase might therefore be of potential interest as a marker for food safety analysis. We herein present an improved diastereoselective synthesis of trichodiene which can be used as an analytical standard for a headspace gas chromatography / mass spectrometry method to be developed. PMID- 25115066 TI - A new source of (R)-limonene and rotundifolone from leaves of Lippia pedunculosa (verbenaceae) and their trypanocidal properties. AB - Investigation by GC-FID and GC-MS of the essential oil (LPOE) from the leaves of Lippia pedunculosa revealed, as the major compounds, the monoterpenes rotundifolone (71.7%) and (R)-limonene (21.8%). These two compounds and the minor constituent piperitenone (1.2%) were also isolated from the leaves and identified by spectrometric analysis. LPOE and isolated compounds were evaluated for their trypanocidal activity against epimastigote and trypomastigote forms of Trypanosoma cruzi. Significant results with IC50 values lower than 34.0 microg.mL(-1) were observed against these forms of T. cruzi for LPOE and isolated compounds. Rotundifolone was the most active compound with an ICso lower than 10.0 ig.mL"' for both forms of T. cruzi. The effects of LPOE and isolated compounds were also evaluated in cultures of macrophages infected with T. cruzi. Treatment with (R)-limonene and rotundifolone caused a moderate reduction in the percentage of macrophages infected by T. cruzi and in the number of intracellular parasites at concentrations non-toxic to macrophages. PMID- 25115068 TI - Synthesis and insecticidal activities of novel nitrogenous derivatives of celangulin-V. AB - In order to develop new biorational pesticides and clarify the potential structural factors needed for the biological activity of celangulin-V analogues, thirty novel nitrogenous derivatives were designed and synthesized. The single crystal structure of celangulin-V is reported for the first time and provides a more accurate structure than that previously reported. The structures of all the new derivatives were confirmed by either NMR or ESI-MSn analysis. Insecticidal activities of these compounds were tested against the third-instar larvae of Mythimna separata. One derivative (1-6) showed higher insecticidal activity than celangulin-V, with a KD50 of 231.2 microg.g(-1), while two compounds (2-13 and 2 14) exhibited lower insecticidal activities; the others revealed no activity at a concentration of 20 mg mL(-1). The results support the view that celangulin-V has the potential to be a lead structure of semi-synthetic green insecticides. PMID- 25115069 TI - An easy way to pyrimidine based nucleoterpenes. AB - The direct synthesis of N3 substituted pyrimidine nucleoterpenes from uridine, thymidine, and inosine with C5, C10, and C15 side chains and using DBU as the base is described. In all cases the reaction proceeded smoothly in very good yields (85-99%) affording selectively N3 substituted adducts. PMID- 25115070 TI - Diastereoselective addition of diazomethane to zaluzanin A. AB - The diastereoselectivity of diazomethane addition to the conjugated double bond of alpha,beta-unsaturated sesquiterpene lactones was explored using zaluzanin A (1) as a model. Thus, the absolute configuration of 1 was assured by X-ray diffraction analysis including evaluation of Flack and Hooft parameters, and by vibrational circular dichroism spectroscopy of its diacetyl derivative 2, while the absolute configuration of the diazomethane addition product, zaluzanin A pyrazoline (3), was determined by evaluation of the 1H NMR chemical shift changes with respect to 1, and confirmed by X-ray diffraction analysis, again including evaluation of Flack and Hooft parameters. PMID- 25115071 TI - Tauroarenarones A and B, new taurine-containing meroterpenoids from the marine sponge Dysidea sp. AB - Two new taurine-containing meroterpenoids, both arenarone derivatives, tauroarenarone A (1) and tauroarenarone B (2), have been isolated from the Australian marine sponge Dysidea sp. Their structures were established from NMR spectroscopic data. PMID- 25115073 TI - Scalarane sesterterpenes from the Paracel Islands marine sponge Hyrtios sp. AB - A new scalarane sesterterpene, sesterstamide (1), together with four known sesterterpenes (2-5), were isolated from the Paracel Islands marine sponge Hyrtios sp. The chemical structures were established on the basis of spectroscopic analysis and comparison with known compounds. The cytotoxic and antileishmanial activities of the isolated compounds were also evaluated. PMID- 25115074 TI - Novel cucurbitane triterpenoids and anti-cholinesterase activities of constituents from Momordica charantia L. AB - The C-19 epimers of 5beta,19-epoxycucurbita-6,23(E),25(26)-triene-3f,19-diol (1) and 5/,19-epoxy-25-methoxycucurbita-6,23-diene-3beta,19-diol (2) along with (19R,23E)-5beta,19-epoxy-19-methoxycucurbita-6,23,25-trien-3beta-ol (3), (23E) 5beta,19-epoxycucurbita-6,23-diene-3beta,25-diol (4), ligballinol (5), charantin (6) and momordicoside K(7) were isolated from the green fruits of Momordica charantia. The (S)-epimers of 1 and 2 are the first reports in nature. The acetyl and butyryl-cholinesterase inhibitory activities of the isolated compounds were evaluated, and 5 showed the highest activity of these compounds against butyrylcholinesterase (IC50 = 32.20 microM) with a reversible and non-competitive inhibition mode. PMID- 25115072 TI - Stereo and regioselective microbial reduction of the clerodane diterpene 3,12 dioxo-15,16-epoxy-4-hydroxycleroda-13(16),14-diene. AB - The biotransformation of the clerodane diterpene, 3,12-dioxo-15,16-epoxy-4 hydroxy-cleroda-13(16),14-diene (1), obtained from Croton micans var. argyroglossum (Baill.) Mill., was investigated for the first time. Whole cells of Cunninghamella echinulata and Rhizopus stolonifer were used as enzymatic systems, and with both fungi the only biotransformation product obtained was the new ent neo-clerodane diterpene (3R,4S,5S,8S,9R,10S)-3,4-dihydroxy-15,16-epoxy-12-oxo cleroda-13(16),14-diene (2a). The absolute stereochemistry of 2a was inferred by comparison of its optical rotation with those of the chemical reduction product of 1 and its quasienantiomer 2c. PMID- 25115075 TI - Immunomodulatory action of triterpene glycosides isolated from the sea cucumber Actinocucumis typica. Structure-activity relationships. AB - Stimulation of lysosomal activity and ROS formation in mouse peritoneal macrophages by five triterpene glycosides, typicosides A1 (1), A2 (2), B1 (3), C1 (4) and C2 (5) has been studied and compared with their cytotoxic activities. Glycosides 1-3 possess moderate activities, but the most cytotoxic glycoside 5 is not active. Typicoside C1 (4), with low toxicity, was proved to be the most active concerning stimulation of ROS formation. This is the first example of a triterpene glycoside from sea cucumbers with low cytotoxicity, but which demonstrates a strong immunostimulatory effect on mouse peritoneal macrophages in vitro. PMID- 25115076 TI - Chromatographic fingerprint combined with content of asperosaponin VI and antioxidant activity for quality evaluation of wine-fried Dipsaci Radix. AB - Dipsaci Radix, the dry root of Dipsacusasper Wall. ex Henry, is a commonly used traditional Chinese medicine (TCM). A novel comprehensive method was proposed for quality evaluation of wine-fried Dipsaci Radix by an integrated data including three aspects of information: high performance liquid chromatography (HPLC) fingerprint, asperosaponin VI content and antioxidant activity (AA). Various indicators including fingerprint similarity, asperosaponin VI content and AA were respectively employed for quality assessment of processed Dipsaci Radix samples. Results showed that considerable differences existed in quality of processed samples with different processing conditions according to three indicators. Among the factors affecting quality of wine-fried Dipsaci Radix, heating temperature was the most influential factor based on analysis of variance (ANOVA), and should be cautiously controlled. The three evaluation indicators respectively used for optimization of processing technology suggested different optimal conditions of wine-frying. Therefore, a combined indicator based on three evaluation indicators was used for determination of optimal processing condition. Multivariate statistical methods such as Hierarchical Clustering Analysis (HCA) and Principal Components Analysis (PCA) were both employed to classify the processed samples for quality evaluation. To more comprehensively evaluate the quality of wine fried Dipsaci Radix, HPLC fingerprint combined with content of asperosaponin VI and AA may be a reasonable and practical approach. PMID- 25115078 TI - Ring A conformation of aconine and pseudaconine in CDCl3. AB - On the basis of intensive interpretation of the 1H NMR spectroscopic data, the ring A conformation of aconine (1) was speculated as twist boat in CDCl3, and as chair or twist boat in acetone-d6 and pyridine-d5. The ring A of pseudaconine (2) adopts the chair conformation in CDCl3, acetone-d6, and pyridine-ds. Accordingly, the boat conformation of ring A in these two diterpenoid alkaloids in CDCl3 reported in the literature [1] should be revised. The difference in 13C NMR data for the same compound (1 or 2) in two different solvents (CDCl3, pyridine-d5) can be attributed to solvent effects. PMID- 25115077 TI - Morphological, chemical and molecular characterization of Centella asiatica germplasms for commercial cultivation in the Indo-Gangetic plains. AB - Centella asiatica germplasm collected from north, north-eastern and southern parts of India was compared for biomass and centellosides productivity under uniform agro-climatic conditions of the Indo-Gangetic plains at Lucknow. The highest biomass accumulation (411.9 g FW/m2 area) was recorded in accession A from north India, followed by 284.0, 135.7 and 29.2 g FW/m2 in accessions M, B and E from southern, eastern and north-eastern regions, respectively. Accession M possessed the highest asiaticoside content (52.1 mg/gDW) that was 1.58, 2.34 and 21.7 folds more than accessions A, B and E, respectively. The madecassoside level in leaves of accessions B and M was comparable (28.9 and 25.7 mg/gDW) and two folds more than accession A (13.9 mg/gDW). The madecassic and asiatic acid content in leaf tissue of all four accessions remained low in Lucknow. Amplified fragment length polymorphism (AFLP) analysis with 23 primers yielded 696 fragments, 563 of which were polymorphic. Accession M out-grouped with genetic dissimilarity indices of 83, 85 and 95% from accessions A, E and B, respectively. Commercial cultivation of accessions M and A through a four months growth cycle (June to September) in agro-climatic conditions of the Indo-Gangetic plains is suggested. PMID- 25115079 TI - Revised NMR data for 9-O-demethylgalanthine: an alkaloid from Zephyranthes robusta (Amaryllidaceae) and its biological activity. AB - Ongoing studies of Zephyranthes robusta resulted in the isolation of the lycorine type alkaloid previously called carinatine and 10-O-demethylgalanthine. The NMR data given previously for this compound were revised and completed by two dimensional 1H-1H and 1H-13C chemical shift correlation experiments. The name of the isolated compound was corrected to 9-O-demethylgalanthine in accordance with the currently used system of numbering of lycorine-type alkaloids. 9-O Demethylgalanthine and galanthine, a previously isolated alkaloid from Z robusta, were inactive in acetylcholinesterase/butyrylcholinesterase assays (IC50 > 500 microM), but showed important prolyl oligopeptidase inhibition activity. PMID- 25115080 TI - Structure revision of N-mercapto-4-formylcarbostyril produced by Pseudomonas fluorescens G308 to 2-(2-hydroxyphenyl)thiazole-4-carbaldehyde [aeruginaldehyde]. AB - An antibiotic substance isolated from Pseudomonas fluorescens strain G308 was earlier assigned the structure of N-mercapto-4-formylcarbostyril, but computational predictions of the 1H and 13C NMR magnetic shielding tensors show this structure to be incompatible with the published spectroscopic data. The same is true for six quinoline derivatives related to N-mercapto-4-formylcarbostyril by permutation of the O and S atoms. In contrast, 2-(2-hydroxyphenyl)thiazole-4 carbaldehyde [aeruginaldehyde], isolated from Pseudomonas protegens Pf-5, together with the reduced derivative aeruginol, displays spectroscopic data identical with those of the alleged carbostyril derivative. In addition, the published 1H and 13C NMR data are in agreement with those calculated for aeruginaldehyde. We propose that aeruginaldehyde and aeruginol originate from the non-ribosomal peptide synthetase enzymes involved in the siderophores enantio pyochelin (or pyochelin) biosynthetic pathways. PMID- 25115081 TI - Accumulation and function of trigonelline in non-leguminous plants. AB - As part of our studies of the occurrence, biosynthesis, function and human use of trigonelline, we looked at trigonelline-accumulating plant species and at the distribution of trigonelline in different organs of trigonelline-accumulating non leguminous plants. There are many trigonelline-synthesizing plant species, but apart from legume seeds only a few species accumulate high concentrations of trigonelline. We have found only three species that accumulate high levels of trigonelline: Murraya paniculata (orange jessamine), Coffea arabica (coffee) and Mirabilisjalapa (four o'clock flower). Trigonelline was found in all parts of Murraya paniculata seedlings at 4-13 micromol/g fresh weight; more than 70% was distributed in the leaves. In the coffee plant, trigonelline was found in all organs, and the concentrations in the upper stems, including tips (48 micromol/g FW) and seeds (26 micromol/g FW), were higher than in other organs. In Mirabilis jalapa plants, trigonelline was found in leaves, stems, flowers, roots and seeds; the concentration varied from 0.3 to 13 micromol/g FW and was generally higher in young tissues than in mature tissues, except for seeds. Exogenously supplied nicotinamide increases the trigonelline content. The in planta role of trigonelline and the possible use oftrigonelline-accumulating plants in herbal medicine are discussed. PMID- 25115082 TI - Metabolites of the endophytic fungus Penicillium sp. FJ-1 of Acanthus ilicifolius. AB - Two new compounds, named as (2R,3S)-pinobanksin-3-cinnamate (1), and 15alpha hydroxy-(22E,24R)-ergosta-3,5,8(14),22-tetraen-7-one (2), were isolated from the endophytic fungus Penicillium sp. FJ-1 of Acanthus ilicifolius Linn. Their structures were elucidated on the basis of spectroscopic analysis. Additionally, compound 1 exhibited potent neuroprotective effects on corticosterone-damaged PC12 cells, and compound 2 showed potent cytotoxicity on glioma cell lines. PMID- 25115083 TI - Overexpression of cinnamate 4-hydroxylase and 4-coumaroyl CoA ligase prompted flavone accumulation in Scutellaria baicalensis hairy roots. AB - Scutellaria baicalensis Georgi, a species of the Lamiaceae family, is considered as one of the 50 fundamental herbs used in traditional Chinese medicine. In order to enhance flavone (baicalein, baicalin, and wogonin) content in S. baicalensis roots, we overexpressed a single gene of cinnamate 4-hydroxylase (C4H) and 4 coumaroyl coenzyme A ligase (4CL) using an Agrobacterium rhizogenes-mediated system. SbC4H- and Sb4CL-overexpressed hairy root lines enhanced the transcript levels of SbC4H and Sb4CL compared with those in the control and also increased flavones contents by approximately 3- and 2.5-fold, respectively. We successfully engineered the flavone biosynthesis pathway for the production of beneficial flavones in S baicalensis hairy roots. The importance of upstream gene C4H and 4CL in flavone biosynthesis and the efficiency of metabolic engineering in promoting flavone biosynthesis in S. baicalensis hairy roots have been indicated in this study. PMID- 25115084 TI - New isoflavone glycosides from the stems of Dalbergia vietnamensis. AB - Two new isoflavone glycosides, dalspinosin 7-O-beta-D-apiofuranosyl-(1-->6)-beta D-glucopyranoside (1) and caviunin 7-O-(5-O-trans-p-coumaroyl)-beta-D apiofuranosyl-(1-->6)-beta-D-glucopyranoside (2), and two known compounds, caviunin 7-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (3) and caviunin (4) were isolated from the stems of Dalbergia vietnamensis. Their structures were determined by the combination of spectroscopic and chemical methods, including 1D and 2D-NMR spectroscopy, as well as by comparing with the NMR data reported in the literature. PMID- 25115085 TI - A characterization of content, composition and scavenging capacity of phenolic compounds in parsnip roots of various weight. AB - The contents, composition and radical scavenging capacity of phenolic compounds from parsnips of various root weights grown in Serbia were examined. The content of phenolic compounds depended on root size, and the highest content was in the group where the samples with the lowest root size were grouped. The content of phenolic compounds varied from 109.7 to 125.3 micromol of chlorogenic acid per g dry extract, i.e.5470.8 to 6245.1 mg per kg fresh weight. Among the identified compounds were quercetin, kaempferol, apigenin and genkwanin glucosides and hydroxycinnamic and caffeoylshikimic acids. The highest antioxidant capacity was found for the group with the lowest root weight; the IC50 values ranged from 1.59 to 2.49 mg mL(-1). There was positive correlation between the total phenolic content and scavenging capacity, and the kaempferol glucosides content could be an indicator of DPPH scavenging capacity of parsnip roots. PMID- 25115086 TI - Variability of procyanidin type A- and -B trimers content in aerial parts of some Vaccinium species and cultivars. AB - Based on the ethnopharmacological data showing that either wild bilberry leaves or whole aerial parts of the plants have been used as antidiabetic drugs, it can be hypothesized that the controversial results of various clinical and animal investigations may be caused by different contents of the active principles in different aerial parts of the bilberry/blueberry (Vaccinium spp.) plants, as well as by their geographical and seasonal variability. The aim of this study was to compare the content of procyanidin type A- and -B trimers in different parts of wild bilberry (Vaccinium myrtillus L.) and northern highbush blueberry (V. corymbosum L.) cultivars. Stems (60 samples) and leaves (30 samples) of wild bilberries and northern highbush blueberry cultivars 'Ama' and 'North Blue' were collected at different locations in Estonia around the year, and analyzed for the concentration of the target polyphenols by HPLC-MS/MS. The highest content of type A doubly linked trimer, a known antidiabetic substance, was established in the stems of V. myrtillus. These contained up to 100 times more of the active substance than the leaves of V. myrtillus and at least 1000 times more than the leaves of V. corymbosum, whereas the seasonal/geographical variation was nearly tenfold. We suggest using stems of V. myrtillus for future animal and clinical investigations of bilberry preparations against diabetes. PMID- 25115087 TI - Three new isoflavonoids from Erythrina caffra. AB - Three new isoflavonoids, 5,7-dihydroxy-2',4'-dimethoxy-5'-(3-methylbut-2-enyl) isoflavanone (erycaffra A) (1), 5,7-dihydroxy-2',4'-dimethoxy-5'-(2-hydroxy-3 methylbut-3-enyl)isoflavanone (erycaffra B) (2), and 5,7-dihydroxy-6,8-di-(2 hydroxy-3-methylbut-3-enyl)isoflavone (erycaffra C) (3), were isolated from the stem bark of E. caffra Thunb., along with eight known compounds, namely, alpinumisoflavone (4), isoerysenegalensein E (5), beta-amyrin (6), oleanolic acid (7), octacosyl-E-ferulate (8), triacontyl-4-hydroxycinnamate (9), n-tetracosyl p coumarate (10) and octacosan-1-ol (11). The structures were determined on the basis of spectroscopic (1D, 2D-NMR) and MS data and by comparison with literature values. PMID- 25115088 TI - Bijayasaline: a new C-glucosyl-alpha-hydroxydihydrochalcone from the heartwood of Bijayasal (Pterocarpus marsupium). AB - A new C-glucosyl-alpha-hydroxydihydrochalcone derivative, (aS)-3'-C-ff glucopyranosyl-a,3,4,2'4'-pentahydroxydihydrochalcone, named as bijayasaline (1) was isolated from the heartwood of Bijayasal (Pterocarpus marsupium) and characterized on the basis of NMR and circular dichroism (CD) spectral data. Bijayasaline (1) showed potent DPPH free radical scavenging activity. PMID- 25115089 TI - Nelumal A, the active principle of Ligularia nelumbifolia, is a novel aromatase inhibitor. AB - Nelumal A, the active principle of Ligularia nelumbifolia was preliminarily tested as an aromatase inhibitors in HEK293 cells transfected with aromatase cDNA and using anastrazole as the reference drug. This screening revealed that it showed an appreciable level of inhibition. Subsequent experiments aimed to evaluate the aromatase activity and expression in KGN cells confirmed that the title natural product, after an incubation of 48 h, compared favourably with anastrazole (1 microM) in the concentration range 10-30 microM. Moreover, nelumal A (30 microM) abolished the aromatase mRNA expression in the same cell line. PMID- 25115090 TI - Chemical constituents of Dendrobium venustum and their antimalarial and anti herpetic properties. AB - A MeOH extract from the whole plant Dendrobium venustum exhibited significant antimalarial and anti-herpetic activities. Bioassay-guided isolation of the plant extract resulted in the isolation of seven known phenolic compounds. Densiflorol B (3) and phoyunnanin E (6) showed the strongest antimalarial activity and a high selectivity index, whereas gigantol (2), batatasin III (5) and phoyunnanin C (7) exhibited moderate activity. Compounds 2 and 5 also showed weak activity against the Herpes simplex virus. This study is the first report on the chemical and biological activities of D. venustum. PMID- 25115091 TI - HPLC-pDA simultaneous determination and protective effect of Anemarrhena asphodeloides against acute renal failure. AB - We investigated the protective effects against acute renal failure (ARF) of Anemarrhena asphodeloides (AA) and performed simultaneous analysis of three compounds, neomangiferin (1), mangiferin (2), and isomangiferin (3) in AA using a high-performance liquid chromatography-photodiode array. To measure the protective effect of ARF, the levels of reactive oxygen species (ROS) and glutathione depletion were determined using a kit. HPLC analysis was performed using a Gemini Cia column at 40 degrees C. The mobile phase used gradient elution with 1.0% (v/v) aqueous acetic acid (A) and 1.0% (v/v) acetic acid in acetonitrile (B). The flow rate was 1.0 mL/min. In our assay, AA extract inhibits cisplatin-induced production of intracellular ROS. Pre-incubation of AA extracts (10-200 microg/mL) markedly maintained cell viability compared with controls in the noncisplatin-treated cells. Calibration curves of all compounds showed good linearity (r2 > or = 0.9992). Recoveries of the three compounds were 98.9-103.4%. The relative standard deviations of intra- and inter-day precision were 0.07 1.73% and 0.12-1.49%, respectively. The amounts of the three components were 1.22 20.63 mg/g. The AA extract has potential as a therapeutic agent for treatment of ARF. In addition, the established method will help to improve quality control of AA. PMID- 25115092 TI - New rocaglamide derivatives from Vietnamese Aglaia species. AB - Phytochemical analysis of the leaves of different Aglaia species collected in Vietnam yielded eight rocaglamide derivatives, which are responsible for the strong insecticidal activity against Spodoptera littoralis, including rocaglamide A (1), rocaglamide 1 (2), rocaglamide W (3), rocaglamide AB (4), rocaglamide J (5), rocaglaol (6), rocaglamide S (7) and the new rocaglamide AY (8). The structures of these compounds were elucidated through extensive 1D and 2D NMR spectroscopy and analysis of their mass spectrometric (ESI-MS) and HRESIMS data. PMID- 25115093 TI - Oxirapentyns A, B and E from the marine-derived strain of Isaria felina KMM 4639 as stimulators of initial stages of development of agricultural plants. AB - Oxirapentyn A (1), oxirapentyn B (2), and oxirapentyn E (3) were examined for their ability to stimulate growth of seedling roots of barley (Hordeum vulgare L.), buckwheat (Fagopyrum esculentum Moench), corn (Zea mays L.), soy {Glycine max (L.) Merr.}, and wheat (Triticum aestivum L.). It was shown that the stimulatory effects depend on the chemical structure of the oxirapentyns and on the plant species. Compounds 1, and 2 are efficient for growth of seedling roots of barley, and wheat, whereas compound 3, at different concentrations, stimulates growth of seedling roots of maize, soy, and wheat. These compounds can be recommended for field study as plant growth stimulators. PMID- 25115094 TI - Concerning the structure of islandoquinone isolated from the lichen Cetraria islandica. AB - An investigation of the oxidative coupling products of some substituted hydroxynaphthazarins led to a revision of the proposed structure of islandoquinone, previously isolated from the lichen Cetraria islandica, and yielding (7aS*, 13aS*)-6,7a-diethyl-2,5,9,11,12,13a-hexahydroxy-7, 4 dioxabenzo[a]tetracene-1,4,8,13(7aH, 13aH)-tetraone through X-ray diffraction analysis of its 2,11-dimethyl ether. PMID- 25115096 TI - Possible role of fat tissue in the pharmacokinetics of Dodeca-2E,4E,8Z,10E/Z tetraenoic acid isobutylamides after oral administration of Echinacea angustifolia extract in rats. AB - Alkamides are one of the most important constituents of lipophilic extracts of Echinacea angustifolia roots. These compounds play an important role in the versatile pharmacological actions of this plant. The present study aimed to compare the concentrations of isomeric dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides (DTAI) in brain and periepididymal fat tissues and blood plasma of rats. Thirty, 60, 240 and 720 min after the oral administration of E. angustifolia root extract, tissue and plasma concentrations were determined by reversed-phase HPLC with ESI-MS/MS detection. The calculated terminal t1/2 of the mixture of DTAI was 8.28 h, which indicates a relatively slow elimination. In the 0.5-4 h period the brain/plasma and fat/plasma concentration ratios were continuously above 3 and 18, respectively, followed by equilibrium at 12 h. Our results indicate substantial accumulation of alkamides in lipid-rich tissues, which presumably contributes to a maintained pharmacological action. PMID- 25115095 TI - Methodology for porphyrin isolation by high-performance countercurrent chromatography. AB - Countercurrent chromatography is a versatile technique for the isolation of a wide variety of plant substances. However, little attention has been devoted to the application of this technique for the isolation of porphyrins. This class of compounds are of great importance in the medical area and in photocatalysis due to their heterocyclic structure, composed of four modified pyrrol subunits interconnected on their a carbon atoms by methinic bridges. The methanol extract of Gallesia integrifolia was partitioned using different solvents; the dichloromethane fraction was then submitted to countercurrent chromatography. The solvent system composed of n-hexane, ethyl acetate, methanol, and water (1:2.5:2.5:1) was chosen to perform the chromatographic analysis due to the enhanced solubility and the best distribution coefficients of the target compounds. Two porphyrins were isolated by this method and identified as 13(2) hydroxypheophorbide a methyl ester and pheophorbide a, methyl ester. The solvent system proposed provided good distribution coefficients for both substances (1.27 and 1.87, respectively), and a high resolution factor. PMID- 25115097 TI - Ascidian tunicate extracts attenuate rheumatoid arthritis in a collagen-induced murine model. AB - Murine rheumatoid arthritis models are often used to investigate the potential therapeutic effects of candidate drugs. The present study has been conducted in order to investigate the therapeutic efficacy of ascidian tunicate extracts in a collagen-induced arthritis DBA1/J mice model. Four types of formulas, ascidian tunicate extracts (ATE), crude ascidian tunicate glycans (ATEC), ascidian tunicate extracts with licorice extracts (ATEL), and crude ascidian tunicate glycans with licorice extracts (ATECL) were orally administered into DBA/1J mice for 3 weeks and paw edema and thickness were evaluated. Changes in inflammatory proteins and cytokines levels were monitored in hind leg tissues by Western blot and quantitative PCR analysis. The oral administration of ascidian tunicate extracts alleviated paw edema and improved the histological hind leg cartilage status. The extracts also reduced the matrix metalloproteinase-9 (MMP-9) protein and prostaglandin E synthase (PGES) levels. In addition, the extracts-treated groups showed increased interleukin-10 (IL-10) levels compared with the non treated group. These findings suggest that orally administered ascidian tunicate extracts might have potential therapeutic effects for the treatment of rheumatoid arthritis. PMID- 25115098 TI - Dialyzable leukocyte extracts activate TLR-2 on monocytes. AB - Dialyzable leukocyte extracts (DLE) transfer specific cell-mediated immune responses from sensitized donors to non-immune recipients. In addition, DLE have several immunomodulatory effects and are used for the treatment of several infectious and non-infectious diseases. Previous studies showed that human DLE obtained from virus-infected leukocytes and bovine DLE decrease the production of the pro-inflammatory cytokine TNF-alpha in response to bacterial lipopolysaccharide, in vitro and in vivo. In the present work, we inquire as to whether DLE from uninfected human leukocytes have the ability to regulate cytokine production in peripheral blood mononuclear cells (PBMC) in vitro. We observed that PBMC from healthy individuals were able to produce TNF-alpha, IL-12 and IL-10 after stimulation with DLE. Moreover, we identified monocytes as the main cell population that produced TNF-alpha after DLE stimulation. Interestingly, we found that DLE contain unidentified ligands that activate Toll like receptor (TLR)-2. Finally, we observed that DLE directly activated monocytes through TLR-2. These results reveal a new biological activity of DLE, and suggest that part of the immunomodulatory properties of DLE could be attributed to TLR-2 activation on monocytes and to the induction of a pro-inflammatory environment that is crucial for control of infectious diseases. PMID- 25115099 TI - The volatile constituents of Parquetina nigrescens from southwestern Nigeria. AB - The leaf essential oil of Parquetina nigrescens collected from Badary, Nigeria, was obtained by hydrodistillation and analyzed by gas chromatography - mass spectrometry. The essential oil had a simple composition with only five identified components. The oil was dominated by citral (35.0% neral and 53.7% geranial). The high concentration of citral in the essential oil likely contributes to the ethnomedicinal utility and bioactivities associated with this medicinal plant. PMID- 25115100 TI - Seasonal variations in the composition of the essential oils of Lavandula angustifolia (Lamiacae). AB - Seasonal variations in the composition of the essential oils obtained from the same individual (of the same genotype) of Lavandula angustifolia cultivated in Belgrade were determined by GC and GC/MS. The main constituents were 1,8-cineole (7.1-48.4%), linalool (0.1-38.7%), bomeol (10.9-27.7%), beta-phellandrene (0.5 21.2%) and camphor (1.5-15.8%). Cluster analysis showed that the 21 samples collected each month during the vegetation cycle were separable into three main clades with different compositions of essential oils. In the shoots with flowers, inflorescences and fruits of clade I, linalool is dominant, in the young leaves before flowering and old leaves of clade II, 1,8-cineole is dominant. In the young and incompletely developed leaves of clade III, beta-phellandrene is dominant. The composition of the essential oils of lavender depended on the plant part and the stage of development. PMID- 25115101 TI - Chemical composition and antimicrobial activity of the essential oil from Allium hookeri consumed in Xishuangbanna, southwest China. AB - The essential oil from the rhizomes of Allium hookeri Thwaites, obtained by simultaneous distillation extraction, was analyzed by GC-MS. Di-2-propenyl trisulfide (31.8%), diallyl disulfide (28.4%), and dipropyl trisulfide (8.4%) were the main constituents among the thirteen identified components. The essential oil showed strong activity against Aspergillus fumigatus and Candida albicans with MIC (the minimal inhibitory concentration) and MBC (minimal bactericidal concentration) values ranging from 32-64 microg/mL. These results suggest that the essential oil from the rhizomes of A. hookeri could be used as a potential antimicrobial ingredient in the food industry. PMID- 25115102 TI - Chemical composition, and cytotoxic, antioxidant and antibacterial activities of the essential oil from ginseng leaves. AB - Panax ginseng C.A.Meyer is one of the most valuable traditional Chinese medicines. In this study, the essential oil of ginseng leaves (EOGL), collected using hydrodistillation and analyzed by GC/MS, contained a complex mixture of aliphatic (69.0%), terpenoid (21.5%) and aromatic compounds (2.4%). Among 54 components identified, the major ones were palmitic acid (36.1%), beta-farnesene (15.4%), linoleic acid (9.8%) and phytol (5.6%). In the cytotoxicity study, EOGL exhibited obvious cytotoxic activities against different cancer cell lines, including Hela, A549, ZR-75-1, HT-29, SGC7901 and B16 cells. Furthermore, Annexin V-FITC/PI staining assay indicated that EOGL can induce late apoptosis of ZR-75-1 cells, and the percentage of apoptotic cells increased in a concentration dependent manner (0.9% to 5.6% and 67.4%). In addition to this, we also found that EOGL exhibited weak DPPH radical scavenging (12.0 +/- 0.4 mg/mL) and ABTS radical scavenging activities (1.6 +/- 0.1 mg/mL), and showed antibacterial activity against the Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and the Gram-negative bacterium, Escherichia coli. The data suggest that EOGL, which possesses important biological activities, especially significant anticancer activity, could be a potential medicinal resource. PMID- 25115103 TI - Essential oil from leaves of Liquidambar formosana ameliorates inflammatory response in lipopolysaccharide-activated mouse macrophages. AB - The essential oil from Liquidambar formosana leaves (EOLF) was demonstrated to exhibit anti-inflammatory activity in mouse macrophages. EOLF reduced nitrite oxide generation, secretion levels of tumor necrosis factor-alpha and interleukin 6, and expression levels of prointerleukin-beta, inducible nitric oxide synthase, and cyclooxygenase-2 in lipopolysaccharide (LPS)-activated mouse macrophages. EOLF also reduced NLRP3 inflammasome-derived interleukin-1beta secretion. The underlying mechanisms for the EOLF-mediated anti-inflammatory activity were (1) reduction of LPS-induced reactive oxygen species generation; (2) reduction of LPS induced activation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38 MAP kinase; (3) reduction of LPS-induced nuclear factor-kappaBeta activation. Furthermore, 25 compounds were identified in the EOLF using GC-FID and GC-MS and the major compounds were terpinen-4-ol (32.0%), beta-pinene (18.0%), gamma-terpinene (13.8%), and alpha-terpinene (9.7%). We found that LPS induced nitrite oxide generation was inhibited significantly by terpinen-4-ol. Our results indicated that EOLF has anti-inflammatory activity and may provide a molecular rationale for future therapeutic interventions in immune modulation. PMID- 25115104 TI - Accumulation of silicon in cacti native to the United States: characterization of silica bodies and cyclic oligosiloxanes in Stenocereus thurberi, Opuntia littoralis, Opuntia ficus-indica, and Opuntia stricta. AB - Four different cactus species growing in the United States, Stenocereus thurberi growing in Organ Pipe Cactus National Monument, Arizona, Opuntia littoralis and Opuntia ficus-indica, growing on Santa Catalina Island, California, and Opuntia stricta, growing in northern Alabama, were examined for the presence of silica bodies (opaline phytoliths). Silica bodies were found in all four of these cactus species, parallelepiped-shaped crystals in S. thurberi, and starburst-shaped crystalline structures in the three Opuntia species. In addition, the essential oils of the four cactus species were obtained by hydrodistillation and analyzed by gas chromatography - mass spectrometry. To our surprise, S. thurberi, O. littoralis, and O. ficus-indica (but not O. stricta) essential oils contained cyclic oligosiloxanes. To our knowledge, cyclic oligosiloxanes have not been previously found as essential oil components. PMID- 25115105 TI - A phytochemical, pharmacological and clinical profile of Paederia foetida and P. scandens. AB - Paederia foetida and P. scandens are two important and well explored Paederia species (Rubiaceae). P. foetida, which grows mainly in China, Bangladesh, India and Mauritius, has been used in folk medicine for the treatment of inflammation, piles, and diarrhea, while P. scandens is used to treat aches, jaundice, dysentery and dyspepsia as a folk medicine in the southern region of China, Vietnam, India and Japan. This review covers the comprehensive knowledge of the traditional medicinal uses, phytochemistry, pharmacology, toxicology and clinical studies of P. foetida and P. scandens. Phytochemical studies revealed the presence of iridoids, flavonoids, volatile oil, and other metabolites in these two species, which possess versatile bioactivities like antinociceptive, anti inflammatory, antidiarrheal, antitussive and antitumor activities. An injection developed from P. scandens has been clinically used as an analgesic drug. P. foetida and P. scandens have emerged as a good source of traditional medicines. Available scientific references reveal that the biological properties of these two Paederia species have been evaluated by modem pharmacological studies. However, bioguided isolation of active constituent responsible for the medical uses, as well as study of their structure-activity relationship and mode of actions, is urgently needed. PMID- 25115106 TI - The oral microbiome in dental caries. AB - Dental caries is one of the most common chronic and multifactorial diseases affecting the human population. The appearance of a caries lesion is determined by the coexistence of three main factors: acidogenic and acidophilic microorganisms, carbohydrates derived from the diet, and host factors. Socio economic and behavioral factors also play an important role in the etiology of the disease. Caries develops as a result of an ecological imbalance in the stable oral microbiom. Oral microorganisms form dental plaque on the surfaces of teeth, which is the cause of the caries process, and shows features of the classic biofilm. Biofilm formation appears to be influenced by large scale changes in protein expression over time and under genetic control Cariogenic microorganisms produce lactic, formic, acetic and propionic acids, which are a product of carbohydrate metabolism. Their presence causes a decrease in pH level below 5.5, resulting in demineralization of enamel hydroxyapatite crystals and proteolytic breakdown of the structure of tooth hard tissues. Streptococcus mutans, other streptococci of the so-called non-mutans streptococci group, Actinomyces and Lactobacillus play a key role in this process. Dental biofilm is a dynamic, constantly active metabolically structure. The alternating processes of decrease and increase of biofilm pH occur, which are followed by the respective processes of de- and remineralisation of the tooth surface. In healthy conditions, these processes are in balance and no permanent damage to the tooth enamel surface occurs. PMID- 25115108 TI - Modular genetic architecture of the toxigenic plasmid pIS56-63 harboring cry1Ab21 in Bacillus thuringiensis subsp. thuringiensis strain IS5056. AB - Bacillus thuringiensis subsp. thuringiensis IS5056, a strain highly toxic to Trichoplusia ni larvae, produces the newly described Cry1Ab21 delta-endotoxin encoded by a gene located in the 63.8 kb pIS56-63 plasmid. In this report we present the structure and functional similarity of this plasmid to other B. thuringiensis large toxigenic plasmids with particular interest focused on its modular architecture. The 61 open reading frames (ORFs) of the plasmid made four functional modules: (i) M1-mic, the mobile insertion cassette harboring cry1Ab21; (ii) M2-tra, the putative conjugative element; (iii) M3-reg, regulation sequence; and (iv) M4-rep, the ori44 replicon. These modules display similarity to corresponding sequences in distinct B. thuringiensis plasmids, but, in general, not to plasmid of other Bacillus cereus sensu lato. The nucleotide sequence and organization of genes in pIS56-63 were highly similar (80-100%) to those in pHT73 of B. thuringiensis HT73, and in p03 of B. thuringiensis HD771, particularly within the M3-reg and M4-rep modules, and slightly less in M2-tra, the latter of which is composed of two segments exhibiting homology to sequences in pBMB28, pAH187_45, pCT83, and pIS56-85 or to pCT72, pBMB67, p04, and pIS56-68. The tetrapartite structure of the toxigenic pIS56-63 plasmid strongly suggests that its hybrid nature is a result of recombination of various genetic elements originating from different extrachromosomal and chromosomal sources in B. thuringiensis. The presence of cry1Ab21 in the mobile cassette suggests that its occurrence on pIS56-63 resulted from recombination and transposition events during the evolution of the plasmid. PMID- 25115107 TI - Bacteriophages as an alternative strategy for fighting biofilm development. AB - The ability of microbes to form biofilms is an important element of their pathogenicity, and biofilm formation is a serious challenge for today's medicine. Fighting the clinical complications associated with biofilm formation is very difficult and linked to a high risk of failure, especially in a time of increasing bacterial resistance to antibiotics. Bacterial species most commonly isolated from biofilms include coagulase-negative staphylococci, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. The frequent failure of antibiotic therapy led researchers to look for alternative methods and experiment with the use of antibacterial factors with a mechanism of action different from that of antibiotics. Experimental studies with bacteriophages and mixtures thereof, expressing lytic properties against numerous biofilm-forming bacterial species showed that bacteriophages may both prevent biofilm formation and contribute to eradication of biofilm bacteria. A specific role is played here by phage depolymerases, which facilitate the degradation of extracellular polymeric substances (EPS) and thus the permeation of bacteriophages into deeper biofilm layers and lysis of the susceptible bacterial cells. Much hope is placed in genetic modifications of bacteriophages that would allow the equipping bacteriophages with the function of depolymerase synthesis. The use of phage cocktails prevents the development of phage-resistant bacteria. PMID- 25115109 TI - Identification of genomic heterogeneity among Lactococcus lactis strains by plasmid profiling, PFGE and 16S rDNA sequence analysis. AB - Lactococcus lactis strains are used commonly as starters, which contribute to desirable flavour and texture properties known as strain-specific, in dairy industry. Genomic heterogeneity of 30 L. lactis strains originating from Turkey and characterized phenotypically were investigated in this study. Plasmid profiling, PFGE and 16S rDNA sequence analyses were performed to determine the genetic variability of strains. High degree of heterogeneity was detected among the L. lactis strains. Plasmid profiles of strains showed that compared to the plasmid free control strains, namely; L. lactis subsp. lactis IL1403 and L. lactis subsp. cremoris MG1614, all tested strains carried one to ten plasmids with molecular size ranging from 1.5 to 41.5kb. The fingerprints of strains obtained by PFGE from digestion with ApaI, SmaI and I-CeuI restriction endonucleases of chromosomal DNA's were compared with each other. All strains out of four were grouped into a large cluster A with at least 44% similarity level. The other four strains formed a minor duster B, distinctively different from major cluster A. PFGE results were confirmed by 16S rDNA sequence analysis and strains included in cluster B were identified as members of different species. These results suggested that morphologic and biochemical methods should be verified by reliable molecular approaches for the purpose of strain typing. Also, PFGE was found suitable to determine genomic differentiations among inter- and intra species. PMID- 25115111 TI - Clinical and microbiological evaluation of biofilm-gingival interface classification in patients with generalized forms of periodontitis. AB - STUDY OBJECTIVE: In 2008 a new division of periodontal diseases based on the concept of biofilm-gingival interface (BGI), was presented. The aim of this study was to assess whether the proposed BGI categories could be useful in diagnosing patients with generalized forms of both aggressive (gAP) and chronic (gCP) periodontitis. DESIGN AND KEY METHODS: The study group consisted of 40 individuals (17 with gAP and 23 with gCP). All patients were divided into three groups according to the BGI scale: 4 patients with P1 (pockets deeper than 4 mms with bleeding index below 10%), 20 individuals with P2 (pockets deeper than 4 mms with bleeding index 10-50%) and 16 individuals with P3 (pockets deeper than 4 mms with bleeding index above 50%). The presence of bacteria in subgingival plaque was analyzed using the polymerase chain reaction method. RESULTS: Statistically significant differences with respect to all parameters measured were found when patients were grouped according to the BGI scale--they were higher in P3 group. In gAP group A. actinomycetemcomitans and C. rectus were found in a higher numbers. No such differences were observed between P2 and P3 groups. CONCLUSIONS: The BGI scale seems to be helpful in effective and quick classifying of patients into adequate clinical subgroups. PMID- 25115110 TI - Detection of sulfonamide resistance genes via in situ PCR-FISH. AB - Due to the rising use of antibiotics and as a consequence of their concentration in the environment an increasing number of antibiotic resistant bacteria is observed. The phenomenon has a hazardous impact on human and animal life. Sulfamethoxazole is one of the sulfonamides commonly detected in surface waters and soil. The aim of the study was to detect sulfamethoxazole resistance genes in activated sludge biocenosis by use of in situ PCR and/or hybridization. So far no FISH probes for the detection of SMX resistance genes have been described in the literature. We have tested common PCR primers used for SMX resistance genes detection as FISH probes as well as a combination of in situ PCR and FISH. Despite the presence of SMX resistance genes in activated sludge confirmed via traditional PCR, the detection of the genes via microscopic visualization failed. PMID- 25115112 TI - Microarray analysis of retroviral restriction factor gene expression in response to porcine endogenous retrovirus infection. AB - Microarray analysis has been used for screening genes involved in specific biological processes. Many studies have shown that restriction factors may play an important role in xenotransplantation safety, but it is still unclear whether porcine endogenous retroviruses (PERVs) may be inhibited by these factors. Therefore, the present study focused on the microarray analysis retroviral restriction factors gene expression in normal human dermal fibroblasts (NHDFs) in response to PERVs. PERV infectivity was analyzed using a co-culture system of NHDFs and porcine kidney epithelial cells (PK15 cell line). Detection of the copy number of PERV A, PERV B DNA and PERV A, PERV B RNA was performed using real-time Q-PCR and QRT-PCR. The expression of retroviral restriction factor genes was compared between PERV-infected and uninfected NHDF cells using oligonucleotide microarray. The up-regulated transcripts were recorded for two differentially expressed genes (TRIM1, TRIM16) with the use of GeneSpring platform and Significance Analysis of Microarrays. In conclusion, our results suggest that the TRIM family may play an important role in innate immunity to PERV infection. These results can allow a better understanding of restriction mechanism of PERV infection and probably design molecularly targeted therapies in the future. Moreover, knowledge of retroviral restriction factor gene expression in human cells may help to uncover strategies for determining their exact function. Microarray analyses seem to be promising in biological and biomedical studies, however, these results should be further confirmed by research conducted at the protein level. PMID- 25115113 TI - Molecular analysis of JC polyomavirus genotypes circulating among tribal populations of North-Eastern West Bengal, India. AB - There is a resurgence of interest in the study of occurrence, genotype and pathogenic associations of human Polyomaviruses in recent years. In the present study, we have ascertained the presence of human Polyomavirus JC (JCV) in the urine and peripheral blood leukocytes of tribal populations, for the first time in the North-Eastern part of West Bengal State of India. We have also characterized the prevalent genotypes of the non-coding controlregions (NCCRs) of these natural isolates. The result suggests a high incidence of JCV reactivation in the populations assayed. Approximately 25% of the non-immunocompromized tribal men and women, tested positive based on polymerase chain reaction (PCR) analysis, and these results were further confirmed by sequencing of PCR products. Pairwise sequence comparison and alignment of the NCCR sequence of these Indian strains appeared to be comparable and related to the archetypal JCV (CY) and the Tibetan LH3 strains, with some alterations in few key positions. The sequence analyses were done with regard to transcription factor binding to DNA sequence elements of endemic JCV NCCRs. PMID- 25115114 TI - Response of viral specific CD4 T cells to in vitro stimulation with vaccine and wild measles virus strains in vaccinated and naturally infected subjects. AB - With the implementation of the WHO strategic plan for the elimination of measles, the number of measles cases in European Region has decreased. However, outbreaks are still observed. Although most measles cases affect unvaccinated individuals, cases with vaccinated persons are also reported. Furthermore, it was described that a high percentage of young people in Poland exhibit no presence of anti-MeV IgG despite the high level of vaccination covering no less than 97% of the Polish population. Strong evidence exists that immunity to measles is complex and depends on both the humoral and cellular response and although antibodies have been used as correlates of immunity, it is increasingly being considered that antibody-based definitions of vaccine success or failure may be incomplete. Here, we investigated immunity to measles as the reactivity of CD4 T cells to stimulation with vaccine as well as wild strains of measles virus (MeV) isolated in Poland, in young vaccinated persons and subjects infected naturally. Evidence for the presence of MeV-specific memory cells years after infection or vaccination was found, however the cells ofvaccinees and naturally infected subjects reacted differently in contact with wild and vaccine MeV strains. Furthermore, the presence of a significant proportion of non-responder vaccinees was observed. In conclusion, our results may have implications for studies on the monitoring of the complexity of post-vaccine immune response. PMID- 25115116 TI - Trends in antifungal susceptibility of Candida species--one year observation. AB - In the past years opportunistic fungal infections have seriously increased, mainly in immunocompromised patients. The aim of the study was to determine the prevalence of yeast-like fungi in invasive candidiasis and to estimate its susceptibility to chosen antifungal agents. One hundred and sixty strains of yeast-like fungi were cultured from various clinical material: samples from lower respiratory tract, blood, the peritoneal cavity and others. The susceptibility tests were established according to the quantitative E-test method. The Candida genus represented the main etiological factor of invasive candidiasis. The predominant species were: C. glabrata (71/160), C. albicans (34/160), C. krusei (17/160), C. tropicalis (14/160). All tested strains were the most resistant to itraconazole. Candida glabrata presented the 100% susceptibility to amphotericin B and caspofungin and was the least susceptible to itraconazole, posaconazole and voriconazole. Candida albicans was the most susceptible species to all antymicotics. PMID- 25115115 TI - Effects of cryopreservation at -80 degrees C on the formulation and pathogenicity of the obligate aphid pathogen Pandora nouryi. AB - Cryopreservation at -80 degrees C is an alternative to liquid nitrogen storage for Entomophthorales. However, detailed studies about its effects on fungal pathogenicity and formulation are very limited. In the present study, the obligate aphid pathogen Pandora nouryi was formulated as mycelia grown on millet gel granules after preservation as primary spores at -80 degrees C for 3-18 months, although its ability to produce infectious conidia gradually diminished. The sporulation capacity of this granular formulation was reduced to 18.5 x 10(4) conidia/mg after 18 months of storage, which was still higher than that of mycotized aphids. The half-decline time of sporulation capacity was computed as 13.6 months. The infectivity to the green peach aphid Myzus persicae had no significant decline in 12 months. The ability to yield resting spores within host carcasses remained unchanged, and the probability of resting spore formation increased with the conidial concentrations that infect aphids. Therefore, cryopreservation at -80 degrees C exerted a marginal impact on formulation and pathogenicity of P. nouryi and can substitute for costly liquid nitrogen storage in routine laboratory studies. The potential of the formulation in aphid biocontrol can be maintained although there is a risk of losing fungal sporulation ability in long-term preservation. PMID- 25115117 TI - Vasculitis and anaphylactoid shock induced in mice by cell wall extract of the fungus Candida metapsilosis. AB - To investigate whether cell wall mannan from Candida metapsilosis induces vasculitis similar to that in Kawasaki syndrome and anaphylactoid shock in mice, we examined the pathogenic effects of C. metapsilosis cell wall extracts. Our results show that intraperitoneal injection of cell wall extracts induced severe coronary arteritis, and intravenous injection induced acute anaphylactoid shock similar to extracts from Candida albicans (C. albicans). Structural analysis of cell wall mannan from C. metapsilosis using NMR spectroscopy showed it to contain only a-mannan, indicating that a-mannan might be contributing to Candida pathogenicity by inducing coronary arteritis and acute shock. PMID- 25115118 TI - Dibasic esters of ortho-/meta-alkoxyphenylcarbamic acid containing 1 dipropylamino-3-piperidinopropan-1-yl and their antimicrobial activity. AB - In Europe, the presence of microorganisms that have become resistant to antimicrobials as the most significant disease threat has remained. The aim of the current research was to screen the in vitro susceptibility of Staphylococcus aureus, Escherichia coli and Candida albicans to the series of dibasic esters of ortho-/meta-alkoxyphenylcarbamic acid previously known for their local anaesthetic effectiveness and to contribute for the structure - antimicrobial potency relationships study within that class of the compounds. The antimicrobial activity investigation involved determination of the minimum inhibitory concentration (MIC) by applying the microdilution method; quantitative screening was performed on a blood agar (S. aureus), Endo agar (E. coli) or on Sabouraud's agar (C. albicans). The activity against all the microorganisms tested was primarily influenced by the position of alkoxy side chain attached to lipophilic aromatic ring and by its length as well. Inspected meta-alkoxy substituted derivatives have shown higher efficiency against all chosen microorganisms than their ortho-alkoxy positional isomers. The most promising results were observed when investigating the activity of meta-alkoxy substituted molecules against E. coli with the estimated MICs in the range of 12-49 microg/ml. Furthermore, such potency was found to be quasi parabolically dependent on alkoxy chain length achieving a maximum for meta-hexyloxy derivative which has shown MIC= 12 microg/ml. Considered compound was also regarded as the most effective against S. aureus with MIC = 98 microg/ml. Evaluating the potency against C. albicans, it was revealed that no molecule within the tested set displayed MIC < 100 microg/ml. PMID- 25115119 TI - Evaluation of the microbiological quality of conventional and organic leafy greens at the time of purchase from retail markets in Alexandria, Egypt. AB - This is a pioneer study in Egypt that provides some assessment of the microbiological quality of conventional and organic leafy green vegetables that constitute an essential component of the Egyptians' daily diet. A total of 380 samples of unpackaged whole conventional and 84 packaged whole organic leafy greens were collected from retail markets in Alexandria, and analyzed for total aerobic mesophilic count (AMC) and total E. coli count (ECC) using the standard spread plate method. Mean AMC values for organic samples were statistically less (p < 0.05) than those of the corresponding conventional samples. Conventional radish and organic parsley samples had the highest AMC of 7.17 and 7.68 log CFU/g respectively, while conventional green cabbage and organic basil had the lowest AMC of 3.63 and 3.23 log CFU/g respectively. The presence of E. coli in 100% of the studied leafy greens was indicative of potential fecal contamination, in view of open and unhygienic environmental and unsanitary handling conditions, as leafy green items are available for sale by street-vendors. Unsatisfactory AMC and ECC levels encountered in the studied samples, warrant future investigations to determine the potential prevalence of foodborne pathogens, and to identify sources of dominating microorganisms, which could make a contribution to the field of food safety PMID- 25115120 TI - Definitive assignment by multigenome analysis of the gammaproteobacterial genus Thermithiobacillus to the class Acidithiobacillia. AB - The class Acidithiobacillia was established using multiprotein phylogenetic analysis of all the available genomes of the genus Acidithiobacillus (comprising Family I, the Acidithiobacillaceae, of the Acidithiobacillales, the order created for Bergey's Manual of Systematic Bacteriology), and for representative genomes of all available bacterial orders. The Acidithiobacillales contain a second family, the Thermithiobacillaceae, represented by Thermithiobacillus tepidarius, and created on the basis of nearest neighbour 16S ribosomal RNA gene sequence similarities. This could not be included in the original multiprotein analysis as no genome sequence for Thermithio bacillus was available. The publication of the genome sequence of Thermithiobacillus tepidarius in 2013 has enabled phylogenetic assessment of this organism by comparative multigenome analysis. This shows definitively that Thermithiobacillus is a member of the class Acidithiobacillia, distinct from the Acidithiobacillus genus, and confirms it to represent a second family within the Acidithiobacillia. PMID- 25115121 TI - Alternative genotyping of drug-resistant Mycobacterium tuberculosis strains. AB - The aim of the present research was to study the capability of a genotyping method for M. tuberculosis through detection of six VNTR-loci (MIRU10, MIRU26, MIRU31, MIRU39, MIRU40, ETR-A). Loci MIRU10, MIRU26, MIRU40 and ETR-A have exhibited high polymorphism in group non-Beijing, while loci MIRU26 and MIRU31 - in the Beijing family. A combined detection of all six loci for fingerprinting of the isolates both from Beijing and non-Beijing was highly effective (Hunter Gaston index was 0.88 and 0.93 correspondently), especially in areas with limited financial resources and high prevalence of multidrug resistant M. tuberculosis strains. PMID- 25115122 TI - Optimization of culture conditions for exopolysaccharide production by a probiotic strain of Lactobacillus rhamnosus E/N. AB - The effects of culture conditions on exopolysaccharides (EPS) production by a probiotic Lb. rhamnosus E/N have been studied using the Plackett-Burman design. Process optimization was performed in stationary cultures to maximize the production of EPS. In order to verify the optimal conditions, an analysis was performed of EPS production in fermentation culture. Batch fermentation was carried out at working volume of 2.51. The optimal temperature, pH, carbon source, and nitrogen source conditions were 37 degrees C, pH 5.0, galactose, and yeast extract, respectively. EPS production was improved by 210.28 mg/l in stationary cultures compared to 134.2 mg/l in a control grown on commercial MRS medium. The fermentor experiment showed the possibility of increasing EPS biosynthesis by 175.8%. Our results clearly demonstrate that in the case of Lb. rhamnosus E/N specific culture conditions can enhance EPS production for possible application in the industry. PMID- 25115123 TI - Critically appraised topics. 1.5-2 mm of coronal dentin needed for crown buildup UT CAT #2439. PMID- 25115125 TI - Why would you want to weight? PMID- 25115124 TI - Oral and maxillofacial pathology. Case of the month. Myeloid sarcoma with monocytic differentiation. PMID- 25115126 TI - Oral cancer. PMID- 25115127 TI - Routine oral cancer screenings by primary care providers. PMID- 25115128 TI - Oral cancer screening for asymptomatic adults: do the United States Preventive Services Task Force draft guidelines miss the proverbial forest for the trees? PMID- 25115129 TI - Human papillomavirus: the fundamentals of HPV for oral health care providers. AB - Human papillomavirus (HPV) has become widely known as the causative agent of cervical cancer and some oropharyngeal cancers. The development of HPV vaccines has further piqued public interest. As a result, dentists will have increasing numbers of patients who will inquire about oral HPV infection and its prevention by means of vaccination. Dental professionals must be informed. This review provides an overview of HPV, its association with HIV and oropharyngeal cancer, and information on HPV vaccinations. PMID- 25115130 TI - Prevalence of HPV associated oropharyngeal cancer among south Texans. AB - The goal of this study was to begin to assess the prevalence of oropharyngeal cancer among all oral cancers and thus the potential role of human papillomavirus (HPV) in this disease in the south Texas Region served by the University of Texas Health Science Center at San Antonio (UTHSCSA), and University Health System (UHS) in San Antonio, Texas. This health system represents the largest catchment area for oral cancer serving the south Texas populations, extending from the U.S. Mexico border, north to Williamson County, west to Eagle Pass, and east to Gonzales County. With the move towards electronic medical records (EMR) nationwide, our team conducted a feasibility study to answer this question utilizing electronic record coding data across both local networks. PMID- 25115131 TI - Traits of practices with highy-effective periodontal protocols. PMID- 25115133 TI - Rapid electrochemical reduction of Ni(II) generates reactive monolayers for conjugated polymer brushes in one step. AB - This article reports the development of a robust, one-step electrochemical technique to generate surface-bound conjugated polymers. The electrochemical reduction of arene diazonium salts at the surface of a gold electrode is used to generate tethered bromobenzene monolayers quickly. The oxidative addition of reactive Ni(0) across the aryl halide bond is achieved in situ through a concerted electrochemical reduction of Ni(dppp)Cl2. This technique limits the diffusion of Ni(0) species away from the surface and overcomes the need for solution deposition techniques which often require multiple steps that result in a loss of surface coverage. With this electrochemical technique, the formation of the reactive monolayer resulted in a surface coverage of 1.29 * 10(14) molecules/cm(2), which is a 6-fold increase over previously reported results using solution deposition techniques. PMID- 25115132 TI - Ameliorative effects of Monascus pilosus-fermented black soybean (Glycine max L. Merrill) on high-fat diet-induced obesity. AB - The purpose of this study was to examine the antiobesity effects of Monascus pilosus-fermented black soybean (F-BS) in C57BL/6 mice with high-fat diet (HFD) induced obesity. F-BS (oral, 0.5 and 1.0 g/kg per body weight, twice per day) ameliorated obesity by reducing body and liver weight increases, and regulating blood glucose and cholesterol levels in C57BL/6 mice fed a control or HFD with oral administration of F-BS for 12 weeks. F-BS suppressed the growth of epididymal, retroperitoneal, and perirenal fat pads by preventing increases in the adipocyte size. Moreover, the levels of blood glucose, total cholesterol, and leptin were significantly lowered by F-BS administration in a dose-dependent manner. These results indicated that F-BS is a beneficial food supplement for preventing obesity, controlling blood glucose, and lowering cholesterol. Future research strategies should address the mechanisms that selectively regulate obesity, including hyperglycemia and hypercholesterolemia. PMID- 25115134 TI - Influences of motivational contexts on prescription drug misuse and related drug problems. AB - Prescription drug misuse has emerged as a significant problem among young adults. While the effects of motivational contexts have been demonstrated for illicit drugs, the role of motivational contexts in prescription drug misuse remains understudied. Using data from 400 young adults recruited via time-space sampling, we examined the role of motivational contexts in the frequency of misuse of three prescription drug types as well as drug-related problems and symptoms of dependency. Both negative and positive motivations to use drugs are associated with increases in prescription drug misuse frequency. Only negative motivations are associated directly with drug problems and drug dependence, as well as indirectly via prescription pain killer misuse. Addressing positive and negative motivational contexts of prescription drug misuse may not only provide a means to reduce misuse and implement harm reduction measures, but may also inform the content of treatment plans for young adults with prescription drug misuse problems. PMID- 25115135 TI - Denial of urinalysis-confirmed opioid use in prescription opioid dependence. AB - Although research has generally supported the validity of substance use self reports, some patients deny urine-verified substance use. We examined the prevalence and patterns of denying urinalysis-confirmed opioid use in a sample of prescription opioid dependent patients. We also identified characteristics associated with denial in this population of increasing public health concern. Opioid use self-reports were compared with weekly urinalysis results in a 12-week multi-site treatment study for prescription opioid dependence. Among those who used opioids during the trial (n=246/360), 44.3% (n=109) denied urinalysis confirmed opioid use, although usually only once (78%). Overall, 22.9% of opioid positive urine tests (149/650) were denied on self-report. Multivariable analysis found that initially using opioids to relieve pain was associated with denying opioid use. These findings support the use of both self-reports and urine testing in treating prescription opioid dependence. PMID- 25115137 TI - Germany: Health system review. AB - This analysis of the German health system reviews recent developments in organization and governance, health financing, health care provision, health reforms and health system performance. In the German health care system, decision making powers are traditionally shared between national (federal) and state (Land) levels, with much power delegated to self-governing bodies. It provides universal coverage for a wide range of benefits. Since 2009, health insurance has been mandatory for all citizens and permanent residents, through either statutory or private health insurance. A total of 70 million people or 85% of the population are covered by statutory health insurance in one of 132 sickness funds in early 2014. Another 11% are covered by substitutive private health insurance. Characteristics of the system are free choice of providers and unrestricted access to all care levels. A key feature of the health care delivery system in Germany is the clear institutional separation between public health services, ambulatory care and hospital (inpatient) care. This has increasingly been perceived as a barrier to change and so provisions for integrated care are being introduced with the aim of improving cooperation between ambulatory physicians and hospitals. Germany invests a substantial amount of its resources on health care: 11.4% of gross domestic product in 2012, which is one of the highest levels in the European Union. In international terms, the German health care system has a generous benefit basket, one of the highest levels of capacity as well as relatively low cost-sharing. However, the German health care system still needs improvement in some areas, such as the quality of care. In addition, the division into statutory and private health insurance remains one of the largest challenges for the German health care system, as it leads to inequalities. PMID- 25115138 TI - Analysis of the Kenyan distance-running phenomenon. AB - PURPOSE: To investigate the ethnicity of Kenya's most successful international runners, tracking their evolution over the period of their international emergence and current dominance. METHODS: The authors analyzed male track distance events from 800m upwards from all the major global athletics championships from 1964 to 2013, and the annual Top-25 world marathon performances since 1990. RESULTS: The percentage of top-25 marathon performances and medals won by Kenyan and Kalenjin runners have increased over time with Nandi subtribe outperforming the rest of the world outside Africa (r > .70, large effect). However, Europe, North America, Oceania, Asia, and South America decreased over time in top marathon performances and track medals won (r > .70, large effect). The tribe and subtribe distribution was different in the marathon than in the track: Maasais were more likely to feature in medals won in shorter track events than in the top 25 of the world marathon rankings (risk ratio [RR] = 9.67, very large effect). This was also the case for Marakwets (RR = 6.44, very large effect) and Pokots (RR = 4.83, large effect). On the other hand, Keiyos, Kikuyus, Kipsigis, Sabaots, and Tugens were more likely to succeed in the marathon than in shorter track events (RR > 2.0, moderate effect). CONCLUSION: These data emphasize that the previously documented emergence of African distance runners is primarily a Kenyan phenomenon, driven by the Kalenjin tribe and in particular the Nandi subtribe. This supports the complex interaction between genotype, phenotype, and socioeconomic factors driving the remarkable dominance of Kenyan distance runners. PMID- 25115136 TI - Web-based training for primary care providers on screening, brief intervention, and referral to treatment (SBIRT) for alcohol, tobacco, and other drugs. AB - This project evaluated a Web-based multimedia training for primary care providers in screening, brief intervention, and referral to treatment (SBIRT) for unhealthy use of alcohol, tobacco, and other drugs. Physicians (n = 37), physician assistants (n = 35), and nurse practitioners (n = 20) were recruited nationally by email and randomly assigned to online access to either the multimedia training or comparable reading materials. At baseline, compared to non-physicians, physicians reported lower self-efficacy for counseling patients regarding substance use and doing so less frequently. All provider types in both conditions showed significant increases in SBIRT-related knowledge, self-efficacy, and clinical practices. Although the multimedia training was not superior to the reading materials with regard to these outcomes, the multimedia training was more likely to be completed and rated more favorably. Findings indicate that SBIRT training does not have to be elaborate to be effective. However, multimedia training may be more appealing to the target audiences. PMID- 25115139 TI - Croatia: health system review. AB - Croatia is a small central European country on the Balkan peninsula, with a population of approximately 4.3 million and a gross domestic product (GDP) of 62% of the European Union (EU) average (expressed in purchasing power parity; PPP) in 2012. On 1 July 2013, Croatia became the 28th Member State of the EU. Life expectancy at birth has been increasing steadily in Croatia (with a small decline in the years following the 1991 to 1995 War of Independence) but is still lower than the EU average. Prevalence of overweight and obesity in the population has increased during recent years and trends in physical inactivity are alarming. The Croatian Health Insurance Fund (CHIF), established in 1993, is the sole insurer in the mandatory health insurance (MHI) system that provides universal health coverage to the whole population. The ownership of secondary health care facilities is distributed between the State and the counties. The financial position of public hospitals is weak and recent reforms were aimed at improving this. The introduction of concessions in 2009 (public private partnerships whereby county governments organize tenders for the provision of specific primary health care services) allowed the counties to play a more active role in the organization, coordination and management of primary health care; most primary care practices have been privatized. The proportion of GDP spent on health by the Croatian government remains relatively low compared to western Europe, as does the per capita health expenditure. Although the share of public expenditure as a proportion of total health expenditure (THE) has been decreasing, at around 82% it is still relatively high, even by European standards. The main source of the CHIFs revenue is compulsory health insurance contributions, accounting for 76% of the total revenues of the CHIF, although only about a third of the population (active workers) is liable to pay full health care contributions. Although the breadth and scope of the MHI scheme are broad, patients must pay towards the costs of many goods and services, and the right to free health care services has been systematically reduced since 2003, although with exemptions for vulnerable population groups. Configuration of capital and human resources in the health care sector could be improved: for example, homes for the elderly and infirm persons operate close to maximum capacity; psychiatric care in the community is not well developed; and there are shortages of certain categories of medical professionals, including geographical imbalances. Little research is available on the policy process of health care reforms in Croatia. However, it seems that reforms often lack strategic foundations and or projections that could be analysed and scrutinized by the public, and evaluation of reform outcomes is lacking. The overall performance of the health care system seems to be good, given the amount of resources available. However, there is a lack of data to assess it properly. PMID- 25115140 TI - Major complications of cryoballoon catheter ablation for atrial fibrillation and their management. AB - Atrial fibrillation (AF) is the most common symptomatic and sustained cardiac arrhythmia. It affects approximately 2-3 million people in the USA alone with an increased incidence and prevalence worldwide. It is associated, in addition to worsening quality of life, with increased morbidity and mortality especially in poorly controlled AF, affecting mostly those older than 65 years of age. Radiofrequency ablation was found to be a good strategy for focal isolation of pulmonary veins triggering from the vulnerable atrial substrate but is a time consuming procedure and carries the risk of multiple complications like tamponade which could be fatal, atrioesophageal fistula and local thrombus formation at the site of ablation. Cryoballoon ablation with pulmonary vein isolation has emerged in the past few years as a breakthrough novel technology for the treatment of drug-refractory AF. It is a relatively simple alternative for point-by-point radiofrequency ablation of paroxysmal AF and is associated with fewer incidences of fatal complications such as cardiac perforation. As experience with this new tool accumulates, the field faces new challenges in the form of rare compilations including gastroparesis, phrenic nerve palsy, atrioesophageal fistula, pulmonary vein stenosis, thromboembolism pericardial effusion, and tamponade. PMID- 25115142 TI - Monitoring neuromuscular fatigue in team-sport athletes using a cycle-ergometer test. AB - PURPOSE: To compare a novel sprint test on a cycle ergometer with a countermovement-jump (CMJ) test for monitoring neuromuscular fatigue after Australian rules football match play. METHODS: Twelve elite under-18 Australian rules football players (mean +/- SD age 17.5 +/- 0.6 y, stature 184.7 +/- 8.8 cm, body mass 75.3 +/- 7.8 kg) from an Australian Football League club's Academy program performed a short sprint test on a cycle ergometer along with a single CMJ test 1 h prematch and 1, 24, and 48 h postmatch. The cycle-ergometer sprint test involved a standardized warm-up, a maximal 6-s sprint, a 1-min active recovery, and a 2nd maximal 6-s sprint, with the highest power output of the 2 sprints recorded as peak power (PP). RESULTS: There were small to moderate differences between postmatch changes in cycle-ergometer PP and CMJ PP at 1 (ES = 0.49), 24 (ES = -0.85), and 48 h postmatch (ES = 0.44). There was a substantial reduction in cycle-ergometer PP at 24 h postmatch (ES = -0.40) compared with 1 h prematch. CONCLUSIONS: The cycle-ergometer sprint test described in this study offers a novel method of neuromuscular-fatigue monitoring in team-sport athletes and specifically quantifies the concentric component of the fatigue-induced decrement of force production in muscle, which may be overlooked by a CMJ test. PMID- 25115141 TI - [Septic arthritis in adults]. AB - Septic arthritis is a true rheumatological emergency requiring immediate and thoughtful effort for rapid diagnosis establishment and treatment initiation. Children and elderly persons as well as immunocompromised individuals, patients with pre-existing joint damage and with inflammatory rheumatic joint diseases are preferentially affected. Bacteremia, joint surgery and intra-articular injections pose risk situations for the development of joint infections. The most frequent causative organism is Staphylococcus aureus but other relevant pathogens include coagulase-negative staphylococci, streptococci and mycobacteria. Synovial fluid analysis (e.g. appearance, cell count and microbiological examination) is the most important step to establish the diagnosis. The two main components of therapy consist of joint drainage and antibiotic treatment. The approach to periprosthetic joint infections depends on the duration of symptoms, causative organism and individual factors. PMID- 25115143 TI - Increased aggression, improved spatial memory, and reduced anxiety-like behaviour in adult male mice exposed to fluoxetine early in life. AB - RATIONALE: Fluoxetine (Flx; brand names Prozac, Sarafem, Rapiflux), a selective serotonin reuptake inhibitor, is prescribed for the treatment of depression in pregnant women; however, this commonly prescribed medication could affect fetal brain development as Flx crosses the placenta. The available data concerning the anatomical and behavioural consequences of perinatal exposure to Flx during early development on adult behaviour are limited and often contradictory. OBJECTIVES: To further delineate the long-term behavioural effects of altering 5-HT during development, we examined the effects of perinatal Flx exposure on the behaviour of male mice as adults. METHODS: Dams were treated with approximately 25 mg/kg/day of Flx from embryonic day 15 to postnatal day 12, and the behaviour of the adult offspring was assessed. RESULTS: We found that perinatal Flx exposure leads to increased aggression, improved spatial memory, and reduced anxiety-like behaviour. This exposure did not cause memory deficits, changes in sensory processing, or changes in gross motor function. CONCLUSIONS: Our results suggest that while perinatal exposure to Flx may have long-term effects on adult behaviour, these effects appear limited and not necessarily detrimental. PMID- 25115146 TI - Assessment and monitoring of ballistic and maximal upper-body strength qualities in athletes. AB - PURPOSE: To evaluate whether the dynamic strength index (DSI: ballistic peak force/isometric peak force) could be effectively used to guide specific training interventions and detect training-induced changes in maximal and ballistic strength. METHODS: Twenty-four elite male athletes were assessed in the isometric bench press and a 45% 1-repetition-maximum (1RM) ballistic bench throw using a force plate and linear position transducer. The DSI was calculated using the peak force values obtained during the ballistic bench throw and isometric bench press. Athletes were then allocated into 2 groups as matched pairs based on their DSI and strength in the 1RM bench press. Over the 5 wk of training, athletes performed either high-load (80-100% 1RM) bench press or moderate-load (40-55% 1RM) ballistic bench throws. RESULTS: The DSI was sensitive to disparate training methods, with the bench-press group increasing isometric bench-press peak force (P=.035, 91% likely), and the ballistic-bench-throw group increasing bench-throw peak force to a greater extent (P<=.001, 83% likely). A significant increase (P<=.001, 93% likely) in the DSI was observed for both groups. CONCLUSIONS: The DSI can be used to guide specific training interventions and can detect training induced changes in isometric bench-press and ballistic bench-throw peak force over periods as short as 5 wk. PMID- 25115145 TI - The European Medicines Agency approval of ingenol mebutate (Picato) for the cutaneous treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in adults: summary of the scientific assessment of the Committee for Medicinal Products for Human Use (CHMP). AB - BACKGROUND: The European Commission has recently issued a marketing authorisation valid throughout the European Union for ingenol mebutate (Picato) in the cutaneous treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in adults. OBJECTIVES: The objective of this paper is to summarise the scientific review of the application leading to regulatory approval in the EU. The full scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (www.ema.europa.eu). MATERIAL & METHODS: The application was supported by 25 clinical studies, of which 18 were performed in patients with actinic keratosis. RESULTS: The active substance is a pure ingenol angelate obtained from the aerial parts of the plant species Euphorbia peplus by extraction and purification. One tube of ingenol mebutate 150 mcg/g gel or 500 mcg/g gel should be applied once daily to the affected area for 3 or 2 consecutive days on the 'face and scalp' or 'trunk and extremities', respectively. Complete response rate is 42.2% on the 'face and scalp' and 34.1% on the 'trunk and extremities'. The most common side effects are local skin responses including erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation and erosion/ulceration at the application site. CONCLUSIONS: The benefits of ingenol mebutate are its ability to improve the complete response rate of actinic keratosis, the short duration of treatment and the ease of self-application. PMID- 25115147 TI - Association between drinking goal and alcohol use one year after residential treatment: a multicenter study. AB - This study examined whether patients' drinking goals at admission to and discharge from 12 residential alcohol use disorder treatment programs were associated with alcohol-related outcomes at 1-year follow-up. Detoxified patients (N = 289) completed assessments at admission, after treatment, and at 1-year follow-up. Drinking goals of abstinence, conditional abstinence (in principle abstinence but potential occurrence of lapses or drinking, when urges are strong), and controlled drinking changed during treatment and predicted the 1 year follow-up outcomes (abstinence, number of standard drinks, and number of days to the first alcohol use). Goals at discharge had a better predictive value. The goal of abstinence at discharge had better outcomes than conditional abstinence; the poorest had controlled drinking. PMID- 25115148 TI - Defining and evaluating the umbrella species concept for conserving and restoring landscape connectivity. AB - Conserving or restoring landscape connectivity between patches of breeding habitat is a common strategy to protect threatened species from habitat fragmentation. By managing connectivity for some species, usually charismatic vertebrates, it is often assumed that these species will serve as conservation umbrellas for other species. We tested this assumption by developing a quantitative method to measure overlap in dispersal habitat of 3 threatened species-a bird (the umbrella), a butterfly, and a frog-inhabiting the same fragmented landscape. Dispersal habitat was determined with Circuitscape, which was parameterized with movement data collected for each species. Despite differences in natural history and breeding habitat, we found substantial overlap in the spatial distributions of areas important for dispersal of this suite of taxa. However, the intuitive umbrella species (the bird) did not have the highest overlap with other species in terms of the areas that supported connectivity. Nevertheless, we contend that when there are no irreconcilable differences between the dispersal habitats of species that cohabitate on the landscape, managing for umbrella species can help conserve or restore connectivity simultaneously for multiple threatened species with different habitat requirements. PMID- 25115150 TI - Overview of nongynecological samples prepared with liquid-based cytology medium. AB - OBJECTIVE: Liquid-based cytology of nongynecological specimens is commonly used in cytology laboratories throughout the world and various processing methods, such as ThinPrep and SurePath, have been reported. The cytological features and performance of liquid-based cytology for various cytology specimens, including body cavity fluids, urine, brushing specimens and fine-needle aspiration of various lesions, were reviewed and compared with the experience of our laboratory and the literature published in PubMed. STUDY DESIGN: The parameters for the evaluation of liquid-based cytology and conventional smears were described in the various types of specimens. Criteria for the interpretation of nongynecological liquid-based cytology were highlighted to show differences in cell morphology, background and artifacts. RESULTS: The interpretation requires familiarity with the appearance of liquid-based cytology in the various types of preparations to avoid misdiagnosis. CONCLUSIONS: Cell blocks can be prepared with specimens preserved in a liquid-based cytology medium and immunocytochemical stains and molecular testing can be successfully performed. These are important adjuncts in order to reach a definitive diagnosis. PMID- 25115153 TI - Current concepts in cartilage management and rehabilitation. PMID- 25115149 TI - Systematic review: the combined surgical and medical treatment of fistulising perianal Crohn's disease. AB - BACKGROUND: The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required. AIM: To review systematically the literature to assess fistula healing rates with medical treatment (anti-TNF-alpha therapies +/- immunomodulators) or surgical treatment alone, compared with combined medical and surgical treatment in fistulising perianal Crohn's disease (CD). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Two independent reviewers searched the literature. RESULTS: Twenty-four articles were included. The total population was 1139 patients; 460 (40%) received single treatment with either medical or surgical therapy, and 679 (60%) received combined medical and surgical therapy. Eight studies compared single and combination therapy, with a total population of 797 patients (single therapy: n = 448, combination therapy: n = 349). In the single therapy group, 191/448 were in complete remission (43%). This was lower than the healing rate of the combination therapy group 180/349 (52%). No response to therapy was noted in 34% (153/448) of the single therapy group compared with 23% (80/349) of the combination group. CONCLUSIONS: Combined surgical and medical (anti-TNF-alpha +/- immunomodulators) therapy may have additional beneficial effects on perianal fistula healing in patients with Crohn's disease, compared with surgery or medical therapy alone. A well-designed Crohn's perianal fistula clinical trial is required in a multidisciplinary medical and surgical setting, with clearly defined end points of clinical (and likely patient reported outcomes) and radiological healing. PMID- 25115151 TI - Serum salusin-alpha and salusin-beta levels in patients with Behcet's disease. AB - BACKGROUND: Behcet's disease (BD) is a chronic, relapsing, systemic vasculitis of unknown etiology. There is an increased predisposition to insulin resistance and metabolic syndrome (MetS) in BD patients. OBJECTIVE: The aim of this study was to determine serum salusin-alpha and salusin-beta levels in BD patients and healthy controls and to investigate their association with MetS. PATIENTS AND METHODS: Twenty-five BD patients and 25 healthy controls were included in the study. Salusin-alpha and salusin-beta levels were measured in blood samples using ELISA. In addition, BD patients and healthy controls were evaluated in terms of MetS. RESULTS: The mean serum salusin-alpha level in BD patients was significantly lower compared to healthy controls (p = 0.03), whereas the mean serum salusin beta level in BD patients was significantly higher compared to healthy controls (p = 0.03). The mean serum salusin-alpha level was significantly lower in BD patients with MetS compared to BD patients without MetS (p = 0.04). CONCLUSIONS: Serum salusin-alpha level (an anti-atherogenic molecule) was lower, while serum salusin-beta level (a pro-atherogenic molecule) was higher in BD patients. We consider that the decrease in salusin-alpha and the increase in salusin-beta levels contribute to the development of MetS. PMID- 25115154 TI - A systematic review of reporting of rehabilitation in articular-cartilage-repair studies of third-generation autologous chondrocyte implantation in the knee. AB - CONTEXT: Autologous chondrocyte implantation (ACI) is a tissue-engineered surgical technique initially developed for articular cartilage repair of isolated chondral lesions of the knee. Third-generation techniques (ACI3) are now available that deliver autologous cultured chondrocytes into the defect using cell scaffolds. The successful outcomes of these techniques have some dependency on presurgical and postsurgical patient rehabilitation. OBJECTIVES: To determine if the standard of reporting for rehabilitation has improved in ACI3 studies; previous reviews in this field recommended describing the detail of this rehabilitation and patient compliance as integral elements. EVIDENCE ACQUISITION: A computerized search was performed in March 2013. Criteria for inclusion were any studies that evaluated or described the process of ACI3 in the knee and subsequent rehabilitation. The modified Coleman Methodology Score (CMS) was used to rate the standard of reporting of rehabilitation and surgical procedures; review articles were also evaluated for quality using the Strength of Recommendation Taxonomy (SORT). Mean scores, odds ratios, 95% confidence intervals, and Mann-Whitney U statistics were calculated. EVIDENCE SYNTHESIS: An improvement in mean CMS was seen compared with previous reviews, but rehabilitation reporting scores were lower than their surgical equivalent; significant association was seen between studies with rehabilitator involvement and high scores in the individual CMS rehabilitation element. Predominant SORT scores of 2A indicated medium strength of recommendation. CONCLUSIONS: The CMS provides a general overview of methodological quality, but a more specialized tool to report on the quantitative and qualitative aspects of the rehabilitation process would help raise the standards. It is recommended that rehabilitation therapists be included as key members of research teams and be involved in the design, implementation, and reporting of future studies. PMID- 25115156 TI - Management of osteochondritis dissecans of the knee. AB - The etiology of osteochondritis dissecans is hypothesized as repetitive microtrauma, resulting in an interruption of blood supply. Due to the location of the most common lesions on the medial femoral condyle, impingement of either the medial tibial spine or inferior pole of the patella against the adjacent medial femur may be responsible. It is much more common in athletic males than other groups. This article reviews the current treatment options for lesions around the knee. PMID- 25115157 TI - The progression of isokinetic knee strength after matrix-induced autologous chondrocyte implantation: implications for rehabilitation and return to activity. AB - CONTEXT: Matrix-induced autologous chondrocyte implantation (MACI) is an established technique for the repair of knee chondral defects. Despite the reported clinical improvement in knee pain and symptoms, little is known on the recovery of knee strength and its return to an appropriate level compared with the unaffected limb. OBJECTIVE: To investigate the progression of isokinetic knee strength and limb symmetry after MACI. DESIGN: Prospective cohort. SETTING: Private functional rehabilitation facility. PATIENTS: 58 patients treated with MACI for full-thickness cartilage defects to the femoral condyles. INTERVENTION: MACI and a standardized rehabilitation protocol. MAIN OUTCOME MEASURES: Preoperatively and at 1, 2, and 5 y postsurgery, patients underwent a 3 repetition-maximum straight-leg raise test, as well as assessment of isokinetic knee-flexor and -extensor torque and hamstring:quadriceps (H:Q) ratios. Correlation analysis investigated the association between strength and pain, demographics, defect, and surgery characteristics. Linear-regression analysis estimated differences in strength measures between the operated and nonoperated limbs, as well as Limb Symmetry Indexes (LSI) over time. RESULTS: Peak knee extension torque improved significantly over time for both limbs but was significantly lower on the operated limb preoperatively and at 1, 2, and 5 y. Mean LSIs of 77.0%, 83.0%, and 86.5% were observed at 1, 2, and 5 y, respectively, while 53.4-72.4% of patients demonstrated an LSI < or = 90% across the postoperative timeline. Peak knee-flexion torque was significantly lower on the operated limb preoperatively and at 1 year. H:Q ratios were significantly higher on the operated limb at all time points. CONCLUSIONS: While peak knee flexion and hip-flexor strength were within normal limits, the majority of patients in this study still demonstrated an LSI for peak knee-extensor strength < or = 90%, even at 5 y. It is unknown how this prolonged knee-extensor deficit may affect long-term graft outcome and risk of reinjury after return to activity. PMID- 25115158 TI - Quadriceps femoris strength and sagittal-plane knee biomechanics during stair ascent in individuals with articular cartilage defects in the knee. AB - CONTEXT: Few objective data are available regarding strength and movement patterns in individuals with articular cartilage defects (ACDs) of the knee. OBJECTIVES: To test the following hypotheses: (1) The involved limb of individuals with ACDs would demonstrate lower peak knee-flexion angle, peak internal knee-extension moment, and peak vertical ground-reaction force (vGRF) than the contralateral limb and healthy controls. (2) On the involved limb of individuals with ACDs, quadriceps femoris strength would positively correlate with peak knee-flexion angle, peak internal knee-extension moment, and peak vGRF. DESIGN: Cross-sectional. SETTING: Biomechanics research laboratory. PARTICIPANTS: 11 individuals with ACDs in the knee who were eligible for surgical cartilage restoration and 10 healthy controls. METHODS: Quadriceps femoris strength was quantified as peak isometric knee-extension torque via an isokinetic dynamometer. Sagittal-plane knee kinematics and kinetics were measured during the stance phase of stair ascent with 3-dimensional motion analysis. MAIN OUTCOME MEASURES: Quadriceps strength and knee biomechanics during stair ascent were compared between the involved and contralateral limbs of participants with ACD (paired t tests) and with a control group (independent-samples t tests). Pearson correlations evaluated relationships between strength and stair-ascent biomechanics. RESULTS: Lower quadriceps strength and peak internal knee-extension moments were observed in the involved limb than in the contralateral limb (P < .01) and the control group (P < .01). For the involved limb of the ACD group, quadriceps femoris strength was strongly correlated (r = .847) with involved-limb peak internal knee-extension moment and inversely correlated (r = -.635) with contralateral peak vGRF. CONCLUSIONS: Individuals with ACDs demonstrated deficits in quadriceps femoris strength with associated alterations in movement patterns during stair ascent. The results of this study are not comprehensive; further research is needed to understand the physiological characteristics, activity performance, and movement quality in this population. PMID- 25115160 TI - Training recruiters to randomized trials to facilitate recruitment and informed consent by exploring patients' treatment preferences. AB - BACKGROUND: Patients' treatment preferences are often cited as barriers to recruitment in randomized controlled trials (RCTs). We investigated how RCT recruiters reacted to patients' treatment preferences and identified key strategies to improve informed decision-making and trial recruitment. METHODS: Audio-recordings of 103 RCT recruitment appointments with 96 participants in three UK multicenter pragmatic RCTs were analyzed using content and thematic analysis. Recruiters' responses to expressed treatment preferences were assessed in one RCT (ProtecT - Prostate testing for cancer and Treatment) in which training on exploring preferences had been given, and compared with two other RCTs where this specific training had not been given. RESULTS: Recruiters elicited treatment preferences similarly in all RCTs but responses to expressed preferences differed substantially. In the ProtecT RCT, patients' preferences were not accepted at face value but were explored and discussed at length in three key ways: eliciting and acknowledging the preference rationale, balancing treatment views, and emphasizing the need to keep an open mind and consider all treatments. By exploring preferences, recruiters enabled participants to become clearer about whether their views were robust enough to be sustained or were sufficiently weak that participation in the RCT became possible. Conversely, in the other RCTs, treatment preferences were often readily accepted without further discussion or understanding the reasoning behind them, suggesting that patients were not given the opportunity to fully consider all treatments and trial participation. CONCLUSIONS: Recruiters can be trained to elicit and address patients' treatment preferences, enabling those who may not have considered trial participation to do so. Without specific guidance, some RCT recruiters are likely to accept initial preferences at face value, missing opportunities to promote more informed decision-making. Training interventions for recruiters that incorporate key strategies to manage treatment preferences, as in the ProtecT study, are required to facilitate recruitment and informed consent. TRIAL REGISTRATION: ProtecT RCT: Current Controlled Trials ISRCTN20141297. The other two trials are registered but have asked to be anonymized. PMID- 25115162 TI - The renin-angiotensin system: a possible contributor to migraine pathogenesis and prophylaxis. AB - The presence of a tissue-based renin-angiotensin system, independent of the systemic one, has been identified in several organs including the brain. Experimental models have suggested the involvement of the renin-angiotensin system in neurogenic inflammation, susceptibility to oxidative stress, endothelial dysfunction, and neuromodulation of nociceptive transmission, thus potentially contributing to the pathogenesis of migraine. Genetic factors that increase susceptibility to migraine may include angiotensin-converting enzyme polymorphism, although available data are controversial. Clinical studies have suggested that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be effective in migraine prophylaxis. However, further research should clarify whether the postulated preventive effect is attributable to a pharmacological action over and above the antihypertensive effect and should test their tolerability in subjects with normal blood pressure values. In patients with contraindications or not responding to conventional prophylactic drugs and in patients with comorbid arterial hypertension, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be used for migraine prophylaxis. PMID- 25115161 TI - Pigmentation in Drosophila melanogaster reaches its maximum in Ethiopia and correlates most strongly with ultra-violet radiation in sub-Saharan Africa. AB - BACKGROUND: Pigmentation has a long history of investigation in evolutionary biology. In Drosophila melanogaster, latitudinal and altitudinal clines have been found but their underlying causes remain unclear. Moreover, most studies were conducted on cosmopolitan populations which have a relatively low level of genetic structure and diversity compared to sub-Saharan African populations. We investigated: 1) the correlation between pigmentation traits within and between the thorax and the fourth abdominal segment, and 2) their associations with different geographical and ecological variables, using 710 lines belonging to 30 sub-Saharan and cosmopolitan populations. RESULTS: Pigmentation clines substantially differed between sub-Saharan and cosmopolitan populations. While positive correlations with latitude have previously been described in Europe, India and Australia, in agreement with Bogert's rule or the thermal melanism hypothesis, we found a significant negative correlation in Africa. This correlation persisted even after correction for altitude, which in its turn showed a positive correlation with pigmentation independently from latitude. More importantly, we found that thoracic pigmentation reaches its maximal values in this species in high-altitude populations of Ethiopia (1,600-3,100 m). Ethiopian flies have a diffuse wide thoracic trident making the mesonotum and the head almost black, a phenotype that is absent from all other sub-Saharan or cosmopolitan populations including high-altitude flies from Peru (~3,400 m). Ecological analyses indicated that the variable most predictive of pigmentation in Africa, especially for the thorax, was ultra-violet (UV) intensity, consistent with the so-called Gloger's rule invoking a role of melanin in UV protection. CONCLUSION: Our data suggest that different environmental factors may shape clinal variation in tropical and temperate regions, and may lead to the evolution of different degrees of melanism in different high altitude populations in the tropics. PMID- 25115164 TI - Effect of multivitamin versus multivitamin-mineral supplementation on metabolic profiles and biomarkers of oxidative stress in pregnant women: a double-blind randomized clinical trial. AB - Abstract Objective: This study was designed to determine the favorable effects of received multivitamin versus multivitamin-mineral supplements on metabolic profiles and biomarkers of oxidative stress among Iranian pregnant women. Methods: This double-blind randomized-controlled clinical trial was conducted among 70 pregnant women, primigravida, aged 18-35 years old between 16 and 37 weeks gestation. Subjects were randomly assigned to receive either the multivitamin (n = 35) or multivitamin-mineral supplements (n = 35) for 20 weeks. Fasting blood samples were taken at baseline and after a 20-week intervention to measure lipid profiles and biomarkers of oxidative stress. Results: After 20 weeks of intervention, multivitamin-mineral supplementation resulted in a significant difference on serum triglycerides levels (changes from baseline in multivitamin-mineral group: +6.1 versus in multivitamin group: +45.9 mg/dl, p = 0.04) compared with the multivitamin group. In addition, increased concentrations of serum HDL-cholesterol (changes from baseline in multivitamin-mineral group: +0.1 versus in multivitamin group: -7.4 mg/dl, p = 0.02) and total glutathione (GSH) levels (changes from baseline in multivitamin-mineral group: +151.09 versus in multivitamin group: -116.21 umol/l, p = 0.003) were also seen in the multivitamin-mineral group compared with the multivitamin group. Conclusion: Supplementation of multivitamin-mineral compared to multivitamin supplementation for 20 weeks during pregnancy had beneficial effects on triglycerides, HDL cholesterol and GSH levels. PMID- 25115165 TI - Nutritional practice effectiveness to achieve adequate plasma vitamin A, E and D during the early postnatal life in Tunisian very low birth weight infants. AB - Abstract Objective: To look at changes in plasma vitamin A, E and D concentrations during the early postnatal life and to study their link with growth and mortality in Tunisian very low birth weight (VLBW) infants. Patients and methods: A cohort of 607 VLBW infants had been followed from birth until hospital discharge or death. Blood was collected at birth, at time of maximal weight loss and at time of recovering birth weight. Retinol and alpha-tocopherol were analyzed using HPLC and 25 hydroxy vitamin D using radioimmunoassay. Results: Vitamin A, D and E deficiencies were very common at birth (75.9%, 74.1% and 65.2%, respectively). The prevalence's have decreased throughout hospital stay, but remained high at time of recovering birth weight (59.4%, 31.2% and 28.8%, respectively). Vitamin A deficiency was associated with longer hospital stay [OR (95% CI), 1.66 (1.03-2.93)] and vitamin E deficiency was associated with increased neonatal mortality [1.44 (1.01-2.23)]. Conclusions: Current nutritional practices are ineffective to achieve adequate vitamins A, E and D status in Tunisian VLBW infants during the early postnatal life and should be revised. Further work is needed to establish recommended doses of vitamins supplements in these preterm infants. PMID- 25115166 TI - Randomized trial of intensive motivational interviewing for methamphetamine dependence. AB - An intensive, 9-session motivational interviewing (IMI) intervention was assessed using a randomized clinical trial of 217 methamphetamine (MA) dependent individuals. Intensive motivational interviewing (IMI) was compared with a single standard session of MI (SMI) combined with eight nutrition education sessions. Interventions were delivered weekly over 2 months. All study participants also received standard outpatient group treatment three times per week. Both study groups showed significant decreases in MA use and Addiction Severity Index drug scores, but there were no significant differences between the two groups. However, reductions in Addiction Severity Index psychiatric severity scores and days of psychiatric problems during the past 30 days were found for clients in the IMI group but not the SMI group. SMI may be equally beneficial to IMI in reducing MA use and problem severity, but IMI may help alleviate co-occurring psychiatric problems that are unaffected by shorter MI interventions. Additional studies are needed to assess the problems, populations, and contexts for which IMI is effective. PMID- 25115167 TI - Laparoscopic versus open partial nephrectomy for multilocular cystic renal cell carcinoma: a direct comparison based on single-center experience. AB - OBJECTIVES: To compare the treatment of laparoscopic (LPN) versus open partial nephrectomy (OPN) in patients with multilocular cystic renal cell carcinoma (MCRCC). METHODS: Thirty-seven patients diagnosed with MCRCC were reviewed retrospectively between January 2007 and January 2013 at our institution. They were divided into two groups: group 1 (LPN) consisted of 19 patients (51.4%) and group 2 (OPN) of 18 patients (48.6%). RENAL and the Preoperative Aspects and Dimensions Used for an Anatomical classification were applied to predict perioperative complications, which were graded based on the Clavien-Dindo classification. RESULTS: The two groups were comparable with regard to all of the patients' baseline characteristics. In group 1, the mean operative time was 142.1 min, including the mean warm ischemia time (WIT) of 32.6 min; the mean estimated blood loss (EBL) was 96.1 ml, the mean retroperitoneal drainage lasted 3.6 days, and the mean postoperative hospital stay was 5.3 days. In group 2, the figures were 126.6 and 23.5 min, 223.3 ml, and 4.6 and 8.7 days, respectively. The differences in WIT, EBL, drainage days and hospitalization were statistically significant between both groups (p < 0.05). No recurrence or new lesions occurred in these patients during a mean follow-up of 37.8 months. CONCLUSIONS: Our single center experience suggests that although it remains technically complex, demanding and challenging for MCRCC, LPN can still induce favorable perioperative results and survival rates in MCRCC are comparable with OPN. PMID- 25115163 TI - Maternal plasma fetuin-A concentration is lower in patients who subsequently developed preterm preeclampsia than in uncomplicated pregnancy: a longitudinal study. AB - Objective: Fetuin-A is a negative acute phase protein reactant that acts as a mediator for lipotoxicity, leading to insulin resistance. Intravascular inflammation and insulin resistance have been implicated in the mechanisms of disease responsible for preeclampsia (PE). Maternal plasma concentrations of fetuin-A at the time of diagnosis of preterm PE are lower than in control patients with a normal pregnancy outcome. However, it is unknown if the changes in maternal plasma fetuin-A concentrations precede the clinical diagnosis of the disease. We conducted a longitudinal study to determine whether patients who subsequently developed PE had a different profile of maternal plasma concentrations of fetuin-A as a function of gestational age (GA) than those with uncomplicated pregnancies. Methods: A longitudinal case-control study was performed and included 200 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered appropriate for gestational age (AGA) neonates (n = 160); and (2) patients who subsequently developed PE (n = 40). Longitudinal samples were collected at each prenatal visit and scheduled at 4-week intervals from the first or early second trimester until delivery. Plasma fetuin-A concentrations were determined by ELISA. Analysis was performed using mixed-effects models. Results: The profiles of maternal plasma concentrations of fetuin-A differ between PE and uncomplicated pregnancies. Forward analysis indicated that the rate of increase of plasma fetuin-A concentration in patients who subsequently developed PE was lower at the beginning of pregnancy (p = 0.001), yet increased faster mid-pregnancy (p = 0.0017) and reached the same concentration level as controls by 26 weeks. The rate of decrease was higher towards the end of pregnancy in patients with PE than in uncomplicated pregnancies (p = 0.002). The mean maternal plasma fetuin-A concentration was significantly lower in patients with preterm PE at the time of clinical diagnosis than in women with uncomplicated pregnancies (p < 0.05). In contrast, there were no significant differences in maternal plasma fetuin-A concentration in patients who developed PE at term. Conclusions: (1) The profile of maternal plasma concentrations of fetuin-A over time (GA) in patients who develop PE is different from that of normal pregnant women; (2) the rate of change of maternal plasma concentrations of fetuin-A is positive (increases over time) in the midtrimester of normal pregnancy, and negative (decreases over time) in patients who subsequently develop PE; (3) at the time of diagnosis, the maternal plasma fetuin A concentration is lower in patients with preterm PE than in those with a normal pregnancy outcome; however, such differences were not demonstrable in patients with term PE. PMID- 25115169 TI - Left ventricular pacing in neonates and infants with isolated congenital complete or advanced atrioventricular block: short- and medium-term outcome. AB - AIMS: Right ventricular (RV) pacing may induce left ventricular (LV) dysfunction: neonates and infants with isolated congenital complete/advanced atrioventricular block (CCAVB) are at high risk of developing RV pacing-induced LV dyssynchrony, remodelling, and dysfunction. We prospectively investigated whether LV pacing results in normal LV function and good clinical status in the short/medium term. METHODS AND RESULTS: In this single-centre, prospective study, 10 consecutive patients with CCAVB (median age 4 months, range: 0.1-16) underwent pacemaker implantation (4 VVIR, 6 DDD) using epicardial leads (on the LV apex in 8, on the LV free wall in 2). Data were collected at implantation and at 1- and 12-month follow-up. Echocardiographic evaluation included two-dimensional/three dimensional assessment of LV dimensions, function (ejection fraction, EF), and ventricular synchrony (interventricular and intraventricular dyssynchrony). Prior to pacemaker implantation, EF was normal in six patients, 50% in two, <=40% in two. All patients showed good clinical status and normal LV dimensions at follow up. Patients with LV dilatation and impaired EF at implantation showed LV reverse remodelling and enhanced LV function. Normal LV function and synchrony were observed in most patients (one patient with EF 53% and three patients with mild dyssynchrony at 12-month follow-up). Paced QRS complex tended to be wider than native QRS complexes (P = 0.07); QTc duration of paced complexes was within normal limits or only slightly prolonged, without significant differences compared with QTc interval of native complexes. CONCLUSION: At short- and medium term follow-up, LV pacing results in satisfactory LV electromechanical function and synchrony in neonates and infants with CCAVB. PMID- 25115170 TI - A descriptive study of elderly patients with dementia who died wandering outdoors in Kochi Prefecture, Japan. AB - This was a descriptive study of elderly persons with dementia who were found dead after becoming lost in the community. Nineteen forensic autopsy cases were performed at Kochi Medical School, Japan. The mean age of the patients (9 males and 10 females) was 82.1 +/- 6.6 years. Causes of death were drowning (n = 8), trauma (n = 5), hypothermia (n = 2), and debilitation possibly due to fatigue (n = 1) or were unknown (n = 3). Thirteen (68%) individuals had been reported missing, most at least 6 hours after they had left. They moved on foot (n = 14), by car (n = 3), or by bicycle (n = 2). Distances from residences to spots of death ranged from 20 to 5800 m for 11 patients on foot. In 8 cases, it was less than 500 m. The study has potential implications for enabling their early discovery and protection. PMID- 25115168 TI - Peri-procedural interrupted oral anticoagulation for atrial fibrillation ablation: comparison of aspirin, warfarin, dabigatran, and rivaroxaban. AB - AIMS: Atrial fibrillation ablation requires peri-procedural oral anticoagulation (OAC) to prevent thromboembolic events. There are several options for OAC. We evaluate peri-procedural AF ablation complications using a variety of peri procedural OACs. METHODS AND RESULTS: We examined peri-procedural OAC and groin, bleeding, and thromboembolic complications for 2334 consecutive AF ablations using open irrigated-tip radiofrequency (RF) catheters. Pre-ablation OAC was warfarin in 1113 (47.7%), dabigatran 426 (18.3%), rivaroxaban 187 (8.0%), aspirin 472 (20.2%), and none 136 (5.8%). Oral anticoagulation was always interrupted and intraprocedural anticoagulation was unfractionated heparin (activated clotting time, ACT = 237 +/- 26 s). Pre- and post-OAC drugs were the same for 1591 (68.2%) and were different for 743 (31.8%). Following ablation, 693 (29.7%) were treated with dabigatran and 291 (12.5%) were treated with rivaroxaban. There were no problems changing from one OAC pre-ablation to another post-ablation. Complications included 12 (0.51%) pericardial tamponades [no differences for dabigatran (P = 0.457) or rivaroxaban (P = 0.163) compared with warfarin], 12 (0.51%) groin complications [no differences for rivaroxaban (P = 0.709) and fewer for dabigatran (P = 0.041) compared with warfarin]. Only 5 of 2334 (0.21%) required blood transfusions. There were two strokes (0.086%) and no transient ischaemic attacks (TIAs) in the first 48 h post-ablation. Three additional strokes (0.13%), and two TIAs (0.086%) occurred from 48 h to 30 days. Only one stroke had a residual deficit. Compared with warfarin, the neurologic event rate was not different for dabigatran (P = 0.684) or rivaroxaban (P = 0.612). CONCLUSION: Using interrupted OAC, low target intraprocedural ACT, and irrigated tip RF, the rate of peri-procedural groin, haemorrhagic, and thromboembolic complications was extremely low. There were only minimal differences between OACs. Low-risk patients may remain on aspirin/no OAC pre-ablation. There are no problems changing from one OAC pre-ablation to another post-ablation. PMID- 25115171 TI - Interaction of anionic phenylene ethynylene polymers with lipids: from membrane embedding to liposome fusion. AB - Here we report spectroscopic studies on the interaction of negatively charged, amphiphilic polyphenylene ethynylene (PPE) polymers with liposomes prepared either from negative, positive or zwitterionic lipids. Emission spectra of PPEs of 7 and 49 average repeat units bearing carboxylate terminated side chains showed that the polymer embeds within positively charged lipids where it exists as free chains. No interaction was observed between PPEs and negatively charged lipids. Here the polymer remained aggregated giving rise to broad emission spectra characteristic of the aggregate species. In zwitterionic lipids, we observed that the majority of the polymer remained aggregated yet a small fraction readily embedded within the membrane. Titration experiments revealed that saturation of zwitterionic lipids with polymer typically occurred at a polymer repeat unit to lipid mole ratio close to 0.05. No further membrane embedding was observed above that point. For liposomes prepared from positively charged lipids, saturation was observed at a PPE repeat unit to lipid mole ratio of ~0.1 and liposome precipitation was observed above this point. FRET studies showed that precipitation was preceded by lipid mixing and liposome fusion induced by the PPEs. This behavior was prominent for the longer polymer and negligible for the shorter polymer at a repeat unit to lipid mole ratio of 0.05. We postulate that fusion is the consequence of membrane destabilization whereby the longer polymer gives rise to more extensive membrane deformation than the shorter polymer. PMID- 25115173 TI - Anesthesia-induced epilepsy: causes and treatment. AB - Epilepsy is a type of chronic brain disease that results from an abnormally high synchronization of neuronal discharge. The typical clinical features of epilepsy are paroxysms and transient and stereotyped brain dysfunction. Many cases of epileptic seizures occurring during anesthesia have been reportedx. Recently, risk assessment of epileptic seizures during surgery and anesthesia has gained increasing attention. In this review, we systematically summarize the influence of anesthesia on epileptic seizures; the types, durations and frequencies of seizures related to anesthesia; and the epidemiology, prevention, treatment and prognosis of epilepsy. We also explore the possible mechanism of epilepsy and provide guidance for anesthesia during surgeries. PMID- 25115172 TI - Reassessing the approach to informed consent: the case of unrelated hematopoietic stem cell transplantation in adult thalassemia patients. AB - INTRODUCTION: The informed consent process is the legal embodiment of the fundamental right of the individual to make decisions affecting his or her health., and the patient's permission is a crucial form of respect of freedom and dignity, it becomes extremely important to enhance the patient's understanding and recall of the information given by the physician. This statement acquires additional weight when the medical treatment proposed can potentially be detrimental or even fatal. This is the case of thalassemia patients pertaining to class 3 of the Pesaro classification where Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment. Unfortunately, this kind of intervention is burdened by an elevated transplantation-related mortality risk (TRM: all deaths considered related to transplantation), equal to 30% according to published reports. In thalassemia, the role of the patient in the informed consent process leading up to HSCT has not been fully investigated. This study investigated the hypothesis that information provided by physicians in the medical scenario of HSCT is not fully understood by patients and that misunderstanding and communication biases may affect the clinical decision-making process. METHODS: A questionnaire was either mailed or given personally to 25 patients. A second questionnaire was administered to the 12 physicians attending the patients enrolled in this study. Descriptive statistics were used to evaluate the communication factors. RESULTS: The results pointed out the difference between the risks communicated by physicians and the risks perceived by patients. Besides the study highlighted the mortality risk considered to be acceptable by patients and that considered to be acceptable by physicians. CONCLUSIONS: Several solutions have been suggested to reduce the gap between communicated and perceived data. A multi-disciplinary approach may possibly help to attenuate some aspects of communication bias. Several tools have also been proposed to fill or to attenuate the gap between communicated and perceived data. But the most important tool is the ability of the physician to comprehend the right place of conscious consent in the relationship with the patient. PMID- 25115175 TI - NBOMe designer drug exposures reported to Texas poison centers. AB - Use of 2-methoxybenzyl analogues of 2C-X phenethylamines (NBOMe) is increasing in the United States. Twenty-five NBOMe exposures reported to Texas poison centers during 2012-2013 were identified; 76% involved 25I-NBOMe, 12% involved 25C-NBOMe, and 12% involved an unknown NBOMe. Eighty-eight percent of the patients were men; mean age was 17 years (range, 14-25 years). The exposure route was 72% from ingestion alone, 12% from inhalation alone, 4% from ingestion and inhalation, and 12% from an unknown route. The most common clinical effects were tachycardia (52%), agitation (48%), hallucinations (32%), hypertension (32%), confusion (24%), and mydriasis (20%). Two patients died. PMID- 25115174 TI - Limited role for ASC and NLRP3 during in vivo Salmonella Typhimurium infection. AB - BACKGROUND: The inflammasome is an intracellular protein complex triggered by exposure to intracellular pathogens, its components or other endogenous proteins. It leads to the activation of and subsequent release of proinflammatory cytokines such as IL-1beta and IL-18. S. Typhimurium is a Gram-negative intracellular bacterium, which is known to trigger inflammasome assembly via recognition by the cytosolic receptors, NLRP3 and NLRC4 (which act via the adaptor protein, ASC) to induce cell death and cytokine release. We sought to characterize the role of ASC and NLRP3 in two different murine models (typhoid and colitis) of systemic Salmonella infection. RESULTS: Release of the inflammasome cytokine IL-18 was hampered in Asc-/- but not Nlrp3-/- mice (background C57BL/6) during S. Typhimurium infection. Unexpectedly, neither ASC nor NLRP3 played a significant role in host defense against S. Typhimurium infection, as reflected by equal bacterial counts in WT, Asc-/- and Nlrp3-/- mice at all time points, in both the typhoid and colitis models. Proinflammatory cytokine levels (TNF-alpha, IL-6) and the extent of hepatic and splenic pathology did not differ between groups in the typhoid model. In the colitis model small differences were seen with regard to splenic and hepatic inflammation, although this was IL-18 independent. CONCLUSIONS: IL-18 release was reduced in Asc-/- but not Nlrp3-/- mice during S. Typhimurium infection. Despite this reduction, bacterial counts, cytokine levels and histological inflammation did not differ between wild-type and knockout mice in either model. Our results reveal a limited role for ASC and NLRP3 during in vivo S. Typhimurium infection despite its role in cytokine maturation. PMID- 25115176 TI - When early life growth restriction in rats is followed by attenuated postnatal growth: effects on cardiac function in adulthood. AB - PURPOSE: Epidemiological and experimental studies demonstrate that intrauterine growth restriction (IUGR) followed by accelerated postnatal growth leads to increased risk of developing cardiac disease in adulthood. The aim of this study was to examine the effect of early life growth restriction on cardiac structure and function in young adult rats. METHODS: IUGR was induced in Wistar Kyoto dams through administration of a low protein diet (LPD; 8.7% casein) during pregnancy and lactation; controls received a normal protein diet (NPD; 20% casein). Cardiac function and structure were assessed in female NPD (n = 7) and LPD (n = 7) offspring at 18 weeks of age by echocardiography and pressure-volume techniques, and systolic blood pressure by tail-cuff sphygmomanometry. RESULTS: LPD offspring remained significantly smaller throughout life compared to controls. There were no differences in the levels of systolic blood pressure, left ventricular cardiac dimensions, heart rate, ejection fraction and fractional shortening of the cardiac muscle between the investigated groups. Aortic peak systolic velocity was significantly reduced in the LPD group (P = 0.02). CONCLUSION: Our findings support the idea that the programming of adult cardiovascular disease can be prevented or delayed in IUGR offspring when postnatal growth trajectory resembles that of in utero. PMID- 25115178 TI - The ADO index as a predictor of two-year mortality in general practice-based chronic obstructive pulmonary disease cohorts. AB - BACKGROUND: Existing prediction models for mortality in chronic obstructive pulmonary disease (COPD) patients have not yet been validated in primary care, which is where the majority of patients receive care. OBJECTIVES: Our aim was to validate the ADO (age, dyspnoea, airflow obstruction) index as a predictor of 2 year mortality in 2 general practice-based COPD cohorts. METHODS: Six hundred and forty-six patients with COPD with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV were enrolled by their general practitioners and followed for 2 years. The ADO regression equation was used to predict a 2-year risk of all-cause mortality in each patient and this risk was compared with the observed 2-year mortality. Discrimination and calibration were assessed as well as the strength of association between the 15-point ADO score and the observed 2 year all-cause mortality. RESULTS: Fifty-two (8.1%) patients died during the 2 year follow-up period. Discrimination with the ADO index was excellent with an area under the curve of 0.78 [95% confidence interval (CI) 0.71-0.84]. Overall, the predicted and observed risks matched well and visual inspection revealed no important differences between them across 10 risk classes (p = 0.68). The odds ratio for death per point increase according to the ADO index was 1.50 (95% CI 1.31-1.71). CONCLUSIONS: The ADO index showed excellent prediction properties in an out-of-population validation carried out in COPD patients from primary care settings. PMID- 25115179 TI - Probing anisotropic surface properties and interaction forces of chrysotile rods by atomic force microscopy and rheology. AB - Understanding the surface properties and interactions of nonspherical particles is of both fundamental and practical importance in the rheology of complex fluids in various engineering applications. In this work, natural chrysotile, a phyllosilicate composed of 1:1 stacked silica and brucite layers which coil into cylindrical structure, was chosen as a model rod-shaped particle. The interactions of chrysotile brucite-like basal or bilayered edge planes and a silicon nitride tip were measured using an atomic force microscope (AFM). The force-distance profiles were fitted using the classical Derjaguin-Landau-Verwey Overbeek (DLVO) theory, which demonstrates anisotropic and pH-dependent surface charge properties of brucite-like basal plane and bilayered edge surface. The points of zero charge (PZC) of the basal and edge planes were estimated to be around pH 10-11 and 6-7, respectively. Rheology measurements of 7 vol % chrysotile (with an aspect ratio of 14.5) in 10 mM NaCl solution showed pH dependent yield stress with a local maximum around pH 7-9, which falls between the two PZC values of the edge and basal planes of the rod particles. On the basis of the surface potentials of the edge and basal planes obtained from AFM measurements, theoretical analysis of the surface interactions of edge-edge, basal-edge, and basal-basal planes of the chrysotile rods suggests the yield stress maximum observed could be mainly attributed to the basal-edge attractions. Our results indicate that the anisotropic surface properties (e.g., charges) of chrysotile rods play an important role in the particle-particle interaction and rheological behavior, which also provides insight into the basic understanding of the colloidal interactions and rheology of nonspherical particles. PMID- 25115177 TI - Short- and long-term effects of a maternal low-energy diet ad libitum during gestation and/or lactation on physiological parameters of mothers and male offspring. AB - PURPOSE: To investigate the short- and long-term effects of a maternal low-energy diet ad libitum during gestation and/or lactation on mothers and their offspring. METHODS: Male Wistar rats were divided into four groups according to their mother's diet: control [C (19.0% protein, 63.0% carbohydrates and 18.0% lipids, total energetic value (TEV) = 3.5 kcal/g) during gestation and lactation], low energy diet (18% protein, 64% carbohydrates and 18% lipids, TEV = 2.3 kcal/g) during gestation (LE-G), low-energy diet during lactation (LE-L) and low-energy diet during gestation and lactation (LE-GL). Additional crude fibers (10% more purified cellulose and soluble fiber) and water (approximately 30% greater moisture) were added to the LE diet to decrease TEV. Mother's body weight, food intake and energy intake were recorded daily. Birth weight, growth rate, ontogeny of reflexes, physical features and biochemical parameters at 150 days old were evaluated in male offspring. RESULTS: Maternal low-energy diet during gestation did not affect maternal body weight and food intake. Physical features did not change but reflex ontogeny was delayed in pups from LE dams. LE-G offspring recovered body size (weight and length) while animals LE-L and LE-GL recovered their body length but remained lighter until adult life even with no change of food intake. LE-G and LE-GL showed lower plasma triglycerides and very-low density-lipoprotein cholesterol (VLDL). LE-L offspring showed hypertriglyceridemia, high VLDL-c and reduced glycaemia. CONCLUSION: Maternal low energy diet shows discernible short- and long-term effects on offspring, and this is dependent on the time of perinatal period. PMID- 25115180 TI - Light and chemical control of neuronal circuits: possible applications in neurotherapy. AB - Millions of people worldwide suffer from diseases that result from a failure of central pathways to regulate behavioral and physiological processes. Advances in genetics and pharmacology have already allowed us to appreciate that rather than this dysregulation being systemic throughout the brain, it is usually rooted in specific subsets of dysfunctional cells within discrete neurological circuits. This article discusses the advent of opto- and chemogenetic tools and how they are providing the means to dissect these circuits with a degree of temporal and spatial sensitivity not previously possible. We also highlight the potential applications for treating disease and the key developments likely to have the greatest impact over the next 5 years. PMID- 25115181 TI - Down-regulation of BTG1 by miR-454-3p enhances cellular radiosensitivity in renal carcinoma cells. AB - BACKGROUND: B cell translocation gene 1 (BTG1) has long been recognized as a tumor suppressor gene. Recent reports demonstrated that BTG1 plays an important role in progression of cell cycle and is involved in cellular response to stressors. However, the microRNAs mediated regulatory mechanism of BTG1 expression has not been reported so far. MicroRNAs can effectively influence tumor radiosensitivity by preventing cell cycle progression, resulting in enhancement of the cytotoxicity of radiotherapy efficacy. This study aimed to demonstrating the effects of microRNAs on the BTG1 expression and cellular radiosensitivity. METHODS: The human renal carcinoma 786-O cells were treated with 5 Gy of X-rays. Expressions of BTG1 gene and miR-454-3p, which was predicted to target BTG1 by software algorithm, were analyzed by quantitative polymerase chain reaction. Protein expressions were assessed by Western blot. Luciferase assays were used to quantify the interaction between BTG1 3'-untranslated region (3'-UTR) and miR-454-3p. The radiosensitivity was quantified by the assay of cell viability, colony formation and caspase-3 activity. RESULTS: The expression of the BTG1 gene in 786-O cells was significantly elevated after treatments with X ray irradiation, DMSO, or serum starvation. The up-regulation of BTG1 after irradiation reduced cellular radiosensitivity as demonstrated by the enhanced cell viability and colony formation, as well as the repressed caspase-3 activity. In comparison, knock down of BTG1 by siRNA led to significantly enhanced cellular radiosensitivity. It was found that miR-454-3p can regulate the expression of BTG1 through a direct interaction with the 3'-UTR of BTG1 mRNA. Decreasing of its expression level correlates well with BTG1 up-regulation during X-ray irradiation. Particularly, we observed that over-expression of miR-454-3p by transfection inhibited the BTG1 expression and enhanced the radiosensitivity. In addition, cell cycle analysis showed that over-expression of miR-454-3p shifted the cell cycle arrest from G2/M phase to S phase. CONCLUSIONS: Our results indicate that BTG1 is a direct target of miR-454-3p. Down-regulation of BTG1 by miR-454-3p renders tumor cells sensitive to radiation. These results may shed light on the potential application in tumor radiotherapy. PMID- 25115183 TI - Getting higher: co-occurring drug use among marijuana-using emerging adults. AB - The most widely used illicit drug in the United States continues to be marijuana, and its use among emerging adults continues to increase. Marijuana use can result in a range of negative consequences and has been associated with other drug use in adolescents and emerging adults. This study examined the relationship between marijuana use frequency and the use of six other drug classes (opiates, cocaine, stimulants, hallucinogens, inhalants, and sleep medications) among emerging adults. A cross-sectional interview design was used with a community sample of 1,075 emerging adults in the northeastern United States. Using logistic regression analysis controlling for age, ethnicity, gender, and frequency of binge alcohol, daily marijuana use was found to be associated with a significant increase in the expected odds of opiate, cocaine, stimulant, hallucinogen, inhalant, and tobacco use. The findings identify a subgroup of emerging adult marijuana users-those who use daily-that may be vulnerable to additional negative consequences associated with polysubstance use. PMID- 25115182 TI - Alternative splicing in osteoclasts and Paget's disease of bone. AB - BACKGROUND: Mutations in the SQSTM1/p62 gene have been reported in Paget's disease of bone (PDB), but they are not sufficient to induce the pagetic osteoclast (OC) phenotype. We hypothesized that specific RNA isoforms of OC related genes may contribute to the overactivity of pagetic OCs, along with other genetic predisposing factors. METHODS: Alternative splicing (AS) events were studied using a PCR-based screening strategy in OC cultures from 29 patients with PDB and 26 healthy donors (HD), all genotyped for the p62P392L mutation. Primer pairs targeting 5223 characterized AS events were used to analyze relative isoform ratios on pooled cDNA from samples of the four groups (PDB, PDBP392L, HD, HDP392L). Of the 1056 active AS events detected in the screening analysis, 192 were re-analyzed on non-amplified cDNA from each subject of the whole cohort. RESULTS: This analysis led to the identification of six AS events significantly associated with PDB, but none with p62P392L. The corresponding genes included LGALS8, RHOT1, CASC4, USP4, TBC1D25, and PIDD. In addition, RHOT1 and LGALS8 genes were upregulated in pagetic OCs, as were CASC4 and RHOT1 genes in the presence of p62P392L. Finally, we showed that the proteins encoded by LGALS8, RHOT1, USP4, TBC1D25, and PIDD were expressed in human OCs. CONCLUSION: This study allowed the identification of hitherto unknown players in OC biology, and our findings of a differential AS in pagetic OCs may generate new concepts in the pathogenesis of PDB. PMID- 25115185 TI - Spreading and arrest of a molten liquid on cold substrates. AB - Understanding the spreading and solidification of liquids on cold solid surfaces is a problem of fundamental importance and general utility. The physics of nonisothermal spreading followed by phase change is still a mystery. The present work focuses on the dynamics and thermal characteristics of liquid drop spreading and their subsequent arrest due to freezing. The spreading of liquid is recorded, and the evolution of the liquid spreading diameter and liquid-solid contact angle is measured from the recordings of a high-speed digital camera. After the initiation of solidification, the liquid drops are pinned to the substrate, showing fixed footprints and contact angles. A physical hypothesis using scaling is provided to explain the relationship between the arrested base diameter (D*) and arrested contact angle (theta*) with respect to the Stefan number (Ste). The experimental observations of solidified drops on cold substrates corroborate the derived physical theory. PMID- 25115187 TI - Identifying correlates of success and failure of native freshwater fish reintroductions. AB - Reintroduction of imperiled native freshwater fish is becoming an increasingly important conservation tool amidst persistent anthropogenic pressures and new threats related to climate change. We summarized trends in native fish reintroductions in the current literature, identified predictors of reintroduction outcome, and devised recommendations for managers attempting future native fish reintroductions. We constructed random forest classifications using data from 260 published case studies of native fish reintroductions to estimate the effectiveness of variables in predicting reintroduction outcome. The outcome of each case was assigned as a success or failure on the basis of the author's perception of the outcome and on whether or not survival, spawning, or recruitment were documented during post-reintroduction monitoring. Inadequately addressing the initial cause of decline was the best predictor of reintroduction failure. Variables associated with habitat (e.g., water quality, prey availability) were also good predictors of reintroduction outcomes, followed by variables associated with stocking (e.g., genetic diversity of stock source, duration of stocking event). Consideration of these variables by managers during the planning process may increase the likelihood for successful outcomes in future reintroduction attempts of native freshwater fish. PMID- 25115184 TI - S-nitrosation of mitochondrial connexin 43 regulates mitochondrial function. AB - S-nitrosation (SNO) of connexin 43 (Cx43)-formed channels modifies dye uptake in astrocytes and gap junctional communication in endothelial cells. Apart from forming channels at the plasma membrane of several cell types, Cx43 is also located at the inner membrane of myocardial subsarcolemmal mitochondria (SSM), but not in interfibrillar mitochondria (IFM). The absence or pharmacological blockade of mitochondrial Cx43 (mtCx43) reduces dye and potassium uptake. Lack of mtCx43 is associated with loss of endogenous cardioprotection by ischemic preconditioning (IPC), which is mediated by formation of reactive oxygen species (ROS). Whether or not mitochondrial Lucifer Yellow (LY), ion uptake, or ROS generation are affected by SNO of mtCx43 and whether or not cardioprotective interventions affect SNO of mtCx43 remains unknown. In SSM from rat hearts, application of NO donors (48 nmol to 1 mmol) increased LY uptake (0.5 mmol SNAP 38.4 +/- 7.1 %, p < 0.05; 1 mmol GSNO 28.1 +/- 7.4 %, p < 0.05) and the refilling rate of potassium (SNAP 227.9 +/- 30.1 %, p < 0.05; GSNO 122.6 +/- 28.1 %, p < 0.05). These effects were absent following blockade of Cx43 hemichannels by carbenoxolone as well as in IFM lacking Cx43. Unlike potassium, the sodium permeability was not affected by application of NO. Furthermore, mitochondrial ROS formation was increased following NO application compared to control SSM (0.5 mmol SNAP 22.9 +/- 1.8 %, p < 0.05; 1 mmol GSNO 40.6 +/- 7.1 %, p < 0.05), but decreased in NO treated IFM compared to control (0.5 mmol SNAP 14.4 +/- 4 %, p < 0.05; 1 mmol GSNO 13.8 +/- 4 %, p < 0.05). NO donor administration to isolated SSM increased SNO of mtCx43 by 109.2 +/- 15.8 %. Nitrite application (48 nmol) to mice was also associated with elevated SNO of mtCx43 by 59.3 +/- 18.2 % (p < 0.05). IPC by four cycles of 5 min of ischemia and 5 min of reperfusion increased SNO of mtCx43 by 41.6 +/- 1.7 % (p < 0.05) when compared to control perfused rat hearts. These data suggest that SNO of mtCx43 increases mitochondrial permeability, especially for potassium and leads to increased ROS formation. The increased amount of SNO mtCx43 by IPC or nitrite administration may link NO and Cx43 in the signal transduction cascade of cardioprotective interventions. PMID- 25115186 TI - Motivationally significant self-control: enhanced action withholding involves the right inferior frontal junction. AB - In everyday life, people use self-control to withhold actions. This ability is particularly important when the consequences of action withholding have an impact on the individual's well-being. Despite its importance, it is unclear as to how the neural nodes implicated in action withholding contribute to this real-world type of self-control. By modifying an action withholding paradigm, the go/no-go task, we examined how the brain exerts self-control during a scenario in which the implications of withholding an action are meaningful and motivationally significant. A successfully withheld response contributed to long-term monetary rewards, whereas failure to withhold a response incurred an immediate monetary punishment. Compared with neutral action withholding, participants significantly improved their performance when these contingencies were applied. Crucially, although the right IFG and pre-SMA were found to promote overall action withholding, the enhancement in behavioral performance relative to a neutral condition was only reflected by a physiological change in a region encompassing the right inferior frontal junction and precentral gyrus. We speculate that the ability to flexibly modulate attention to goal-relevant stimuli is crucial to enhanced, motivationally driven action withholding and that this ability is subserved by the right inferior frontal junction. These findings suggest that control-modulating factors, rather than action withholding processes per se, can be critical to improving motivationally significant action withholding outcomes. PMID- 25115188 TI - Accuracy of cytotechnologist evaluation of specimen adequacy and screening interpretation of malignancy in fine-needle aspiration of the liver. AB - OBJECTIVE: To evaluate the performance of cytotechnologists in assessing the adequacy and accuracy of the preliminary diagnosis for fine-needle aspirates of the liver. STUDY DESIGN: We retrospectively analyzed 10 years of data and found 589 cases of ultrasound-guided fine-needle aspiration (FNA) of the liver with on site evaluation of adequacy (OSEA). All the OSEA were performed by the cytopathologist because OSEA of liver FNA is not performed by cytotechnologists at our institution at present. After OSEA, the material was seen by cytotechnologists who rendered an adequacy assessment and preliminary diagnosis. We calculated the adequacy and accuracy statistics and compared the performance of the cytotechnologists with the OSEA and final interpretation. RESULTS: There was no statistically significant difference in adequacy downgrade rate for cytotechnologist versus cytopathologist assessment during the study period (5 vs. 3%, p = 0.06). A total agreement of 88% was noted in overall diagnosis with 97% agreement in malignant cases. CONCLUSION: Cytotechnologists assess the adequacy of liver FNA accurately and there is therefore potential for them to perform OSEA for liver FNA. PMID- 25115191 TI - Towards developing biomarkers for glioblastoma multiforme: a proteomics view. AB - Glioblastoma multiforme (GBM) is one of the most aggressive and lethal forms of the primary brain tumors. With predominance of tumor heterogeneity and emergence of new subtypes, new approaches are needed to develop tissue-based markers for tumor typing or circulatory markers to serve as blood-based assays. Multi-omics data integration for GBM tissues would offer new insights on the molecular view of GBM pathogenesis useful to identify biomarker panels. On the other hand, mapping differentially expressed tissue proteins for their secretory potential through bioinformatics analysis or analysis of the tumor cell secretome or tumor exosomes would enhance our understanding of the tumor microenvironment and prospects for targeting circulatory biomarkers. In this review, the authors first present potential biomarker candidates for GBM that have been reported and then focus on plausible pipelines for multi-omic data integration to identify additional, high-confidence molecular panels for clinical applications in GBM. PMID- 25115189 TI - The bidirectional tumor--mesenchymal stromal cell interaction promotes the progression of head and neck cancer. AB - INTRODUCTION: Mesenchymal stromal cells (MSC) are an integral cellular component of the tumor microenvironment. Nevertheless, very little is known about MSC originating from human malignant tissue and modulation of these cells by tumor derived factors. The aim of this study was to isolate and characterize MSC from head and neck squamous cell carcinoma (HNSCC) and to investigate their interaction with tumor cells. METHODS: MSC were isolated from tumor tissues of HNSCC patients during routine oncological surgery. Immunophenotyping, immunofluorescence and in vitro differentiation were performed to determine whether the isolated cells met the consensus criteria for MSC. The cytokine profile of tumor-derived MSC was determined by enzyme-linked immunosorbent assay (ELISA). Activation of MSC by tumor-conditioned media was assessed by measuring cytokine release and expression of CD54. The impact of MSC on tumor growth in vivo was analyzed in a HNSCC xenograft model. RESULTS: Cells isolated from HNSCC tissue met the consensus criteria for MSC. Tumor-derived MSC constitutively produced high amounts of interleukin (IL)-6, IL-8 and stromal cell-derived factor (SDF)-1alpha. HNSCC-derived factors activated MSC and enhanced secretion of IL-8 and expression of CD54. Furthermore, MSC provided stromal support for human HNSCC cell lines in vivo and enhanced their growth in a murine xenograft model. CONCLUSIONS: This is the first study to isolate and characterize MSC from malignant tissues of patients with HNSCC. We observed cross-talk of stromal cells and tumor cells resulting in enhanced growth of HNSCC in vivo. PMID- 25115193 TI - Systematic Review of the Manifestations of Congenital Rubella Syndrome in Infants and Characterization of Disability-Adjusted Life Years (DALYs). AB - Congenital rubella syndrome (CRS) continues to cause disability among unvaccinated populations in countries with no or insufficient rubella vaccine coverage to prevent transmission. We systematically reviewed the literature on birth outcomes associated with CRS to estimate the duration, severity, and frequency of combinations of morbidities. We searched PubMed, the Science Citation Index, and references from relevant articles for studies in English with primary data on the frequency of CRS manifestations for >=20 cases and identified 65 studies representing 66 study populations that met our inclusion criteria. We abstracted available data on CRS cases with one or more hearing, heart, and/or eye defect following maternal rubella infection during the period of 0-20 weeks since the last menstrual period. We assessed the quality and weight of the available evidence using a modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Most of the evidence originates from studies in developed countries of cohorts of infants identified with CRS in the 1960s and 1970s, prior to the development of standardized definitions for CRS and widespread use of vaccine. We developed estimates of undiscounted disability adjusted life years (DALYs) lost per CRS case for countries of different income levels. The estimates ranged from approximately 19 to 39 for high-income countries assuming optimal treatment and from approximately 29 to 39 DALYs lost per CRS case in low- and lower- middle-income countries assuming minimal treatment, with the lower bound based on 2010 general global burden of disease disability weights and the upper bound based on 1990 age-specific and treatment specific global burden of disease disability weights. Policymakers and analysts should appreciate the significant burden of disability caused by CRS as they evaluate opportunities to manage rubella. PMID- 25115192 TI - Gene signatures ESC, MYC and ERG-fusion are early markers of a potentially dangerous subtype of prostate cancer. AB - BACKGROUND: Good prognostic tools for predicting disease progression in early stage prostate cancer (PCa) are still missing. Detection of molecular subtypes, for instance by using microarray gene technology, can give new prognostic information which can assist personalized treatment planning. The detection of new subtypes with validation across additional and larger patient cohorts is important for bringing a potential prognostic tool into the clinic. METHODS: We used fresh frozen prostatectomy tissue of high molecular quality to further explore four molecular subtype signatures of PCa based on Gene Set Enrichment Analysis (GSEA) of 15 selected gene sets published in a previous study. For this analysis we used a statistical test of dependent correlations to compare reference signatures to signatures in new normal and PCa samples, and also explore signatures within and between sample subgroups in the new samples. RESULTS: An important finding was the consistent signatures observed for samples from the same patient independent of Gleason score. This proves that the signatures are robust and can surpass a normally high tumor heterogeneity within each patient. Our data did not distinguish between four different subtypes of PCa as previously published, but rather highlighted two groups of samples which could be related to good and poor prognosis based on survival data from the previous study.The poor prognosis group highlighted a set of samples characterized by enrichment of ESC, ERG-fusion and MYC + rich signatures in patients diagnosed with low Gleason score,. The other group consisted of PCa samples showing good prognosis as well as normal samples. Accounting for sample composition (the amount of benign structures such as stroma and epithelial cells in addition to the cancer component) was important to improve subtype assignments and should also be considered in future studies. CONCLUSION: Our study validates a previous molecular subtyping of PCa in a new patient cohort, and identifies a subgroup of PCa samples highly interesting for detecting high risk PCa at an early stage. The importance of taking sample tissue composition into account when assigning subtype is emphasized. PMID- 25115197 TI - Do palliative care interventions reduce emergency department visits among patients with cancer at the end of life? A systematic review. AB - BACKGROUND: Frequent emergency department (ED) visits are an indicator of poor quality of cancer care. Coordination of care through the use of palliative care teams may limit aggressive care and improve outcomes for patients with cancer at the end of life. OBJECTIVES: To systematically review the literature to determine whether palliative care interventions implemented in the hospital, home, or outpatient clinic are more effective than usual care in reducing ED visits among patients with cancer at the end of life. ELIGIBILITY CRITERIA: PubMed, EMBASE, and CINAHL databases were searched from database inception to May 7, 2014. Only randomized/non-randomized controlled trials (RCTs) and observational studies examining the effect of palliative care interventions on ED visits among adult patients with cancer with advanced disease were considered. DATA EXTRACTION AND DATA SYNTHESIS: Data were abstracted from the articles that met all the inclusion criteria. A second reviewer independently abstracted data from 2 articles and discrepancies were resolved. From 464 abstracts, 2 RCTs, 10 observational studies, and 1 non-RCT/quasi-experimental study were included. Overall there is limited evidence to support the use of palliative care interventions to reduce ED visits, although studies examining effect of hospice care and those conducted outside of the United States reported a statistically significant reduction in ED visits. CONCLUSIONS: Evidence regarding whether palliative care interventions implemented in the hospital, home or outpatient clinic are more effective than usual care at reducing ED visits is not strongly substantiated based on the literature reviewed. Improvements in the quality of reporting for studies examining the effect of palliative care interventions on ED use are needed. PMID- 25115194 TI - Survival rate of etanercept for psoriasis in real life: a multicentre observational study. PMID- 25115195 TI - Bridging the gap: Lessons we have learnt from the merging of psychology and psychiatry for the optimisation of treatments for emotional disorders. AB - In recent years the gap between psychological and psychiatric research and practice has lessened. In turn, greater attention has been paid toward how psychological and pharmacological treatments interact. Unfortunately, the majority of research has indicated no additive effect of anxiolytics and antidepressants when combined with psychological treatments, and in many cases pharmacological treatments attenuate the effectiveness of psychological treatments. However, as psychology and psychiatry have come closer together, research has started to investigate the neural and molecular mechanisms underlying psychological treatments. Such research has utilised preclinical models of psychological treatments, such as fear extinction, in both rodents and humans to determine multiple neural and molecular changes that may be responsible for the long-term cognitive and behavioural changes that psychological treatments induce. Currently, researchers are attempting to identify pharmacological agents that directly augment these neural/molecular changes, and which may be more effective adjuncts to psychological treatments than traditional anxiolytics and antidepressants. In this review we describe the research that has led to this new wave of thinking about combined psychological/pharmacological treatments. We also argue that an increased emphasis on identifying individual difference factors that predict the effectiveness of pharmacological adjuncts is critical in facilitating the translation of this preclinical research into clinical practice. PMID- 25115198 TI - From crab shells to smart systems: chitosan-alkylethoxy carboxylate complexes. AB - In this work, self-assembly of alkyl ethylene oxide carboxylates and the biopolymer chitosan into supramolecular structures with various shapes is presented. Our investigations were done at pH 4.0, where the chitosan is almost fully charged and the surfactants are partially deprotonated. By changing the alkyl chain length and the number of ethylenoxide units very different water soluble complexes can be obtained, ranging from globular micelles incorporated in a chitosan network to formation of ordered multiwalled vesicles. The structural characteristics of these complexes can be finely controlled by the mixing ratio of chitosan and surfactant, i.e., simply by the solutions composition. For instance, the vesicle wall thickness can be varied between 5 and 50 nm just by varying the mixing ratio. Accordingly, we expect this system to be an outstanding carrier for hydrophilic compounds with tunable release time option. Moreover, an easy route for preparation of chitosan-based complexes in the solid state with controlled mesoscopic order is presented. This work opens the way to prepare biofriendly materials on the basis of chitosan and mild anionic surfactants which are rather versatile with respect to their structure and properties, allowing for preparation of complexes with highly variable structures in both aqueous and solid phase. Formation of such different structures can be exploited for preparation of carriers, which are able to transport hydrophilic as well as hydrophobic molecules. Furthermore, as chitosan is well known to exhibit antibacterial and anti-inflammatory properties, different applications of these complexes can be indicated, i.e., as drug delivery systems or as coatings for medical implants. PMID- 25115199 TI - Psychosocial correlates of adolescent cannabis use: data from the Italian subsample of the second International Self-Reported Delinquency study. AB - To provide a comprehensive picture of the whole spectrum of psychosocial factors potentially associated with adolescent cannabis use, bivariate and multivariate analyses were used to assess a variety of social, demographic, psychological, and behavioral correlates of last-month cannabis use and age of first use among 6,838 students. Results showed that only family problems, alcohol and/or other drug use/misuse, deviant behavior, and victimization were independently associated with either recent cannabis use or early onset of cannabis use when multiple, interacting factors were considered. Certain family and behavioral factors might be more important than other psychosocial correlates of adolescent cannabis use. PMID- 25115200 TI - Associations between follow-up screening after gestational diabetes and early detection of diabetes--a register based study. AB - BACKGROUND: Women whose pregnancy was complicated by gestational diabetes have a 7-fold higher risk of developing diabetes, primarily type 2. Early detection can prevent or delay the onset of late complications, for which follow-up screening is important. This study investigated the extent of participation in follow-up screening and the possible consequences of nonattendance in the Region of North Jutland, Denmark. METHOD: In Danish national registers covering the years 1994 2011 we identified 2171 birthing women whose pregnancy was complicated by first time gestational diabetes. Control visits to general practitioners and biochemical departments after giving birth were charted. Following national guidelines we defined four intervals for assessment of participation in follow-up screening. Diagnosis of diabetes or treatment with glucose-lowering agents after giving birth were also identified. Participation in follow-up screening and risk of diabetes was calculated. Time to obtaining diagnosis of diabetes or initiating treatment was analysed by Cox regression models. All models were adjusted for age, ethnicity and income. RESULTS: High attendance was found during the first control interval, after which attendance decreased with time after giving birth for both controls at general practitioners and biochemical departments. All differences in proportions were statistically significant. Women attending controls at general practitioners had a significantly higher risk of diabetes diagnosis and treatment after gestational diabetes than women not attending. The results for women attending testing at biochemical departments also showed an increased risk of initiation of treatment. Women attending at least one general practitioners control had a significantly higher risk of early diabetes diagnosis or treatment. Time to initiation of treatment was significantly higher for testing at biochemical departments. Women with high incomes had a significantly lower risk of diabetes diagnosis or initiation of treatment compared to low income women. CONCLUSION: Participation in follow-up screening after gestational diabetes is low in the North Denmark Region. Follow-up screening ensures early detection of diabetes and initiation of treatment. Our results emphasize the importance of development of interventions to improve early detection and prevention of diabetes after gestational diabetes. PMID- 25115201 TI - The p-EVES study design and methodology: a randomised controlled trial to compare portable electronic vision enhancement systems (p-EVES) to optical magnifiers for near vision activities in visual impairment. AB - PURPOSE: To describe the study design and methodology for the p-EVES study, a trial designed to determine the effectiveness, cost-effectiveness and acceptability of portable Electronic Vision Enhancement System (p-EVES) devices and conventional optical low vision aids (LVAs) for near tasks in people with low vision. METHODS: The p-EVES study is a prospective two-arm randomised cross-over trial to test the hypothesis that, in comparison to optical LVAs, p-EVES can be: used for longer duration; used for a wider range of tasks than a single optical LVA and/or enable users to do tasks that they were not able to do with optical LVAs; allow faster performance of instrumental activities of daily living; and allow faster reading. A total of 100 adult participants with visual impairment are currently being recruited from Manchester Royal Eye Hospital and randomised into either Group 1 (receiving the two interventions A and B in the order AB), or Group 2 (receiving the two interventions in the order BA). Intervention A is a 2 month period with conventional optical LVAs and a p-EVES device, and intervention B is a 2-month period with conventional optical LVAs only. RESULTS: The study adopts a mixed methods approach encompassing a broad range of outcome measures. The results will be obtained from the following primary outcome measures: Manchester Low Vision Questionnaire, capturing device 'usage' data (which devices are used, number of times, for what purposes, and for how long) and the MNRead test, measuring threshold print size, critical print size, and acuity reserve in addition to reading speed at high (~90%) contrast. Results will also be obtained from a series of secondary outcome measures which include: assessment of timed instrumental activities of daily living and a 'near vision' visual functioning questionnaire. A companion qualitative study will permit comparison of results on how, where, and under what circumstances, p-EVES devices and LVAs are used in daily life. A health economic evaluation will provide results on: the incremental cost-effectiveness of p-EVES compared to optical magnifiers; cost-effectiveness; and cost-utility. CONCLUSIONS: The evidence base in low vision rehabilitation is modest and further high quality clinical trials are required to inform decisions on healthcare provision. The p-EVES study findings are anticipated to contribute to this broader evidence requirement, with the methodological issues evident here being relevant to other trials within the field. PMID- 25115203 TI - Porokeratoses: an update of clinical, aetiopathogenic and therapeutic features. AB - Porokeratoses represent a group of uncommon, acquired or hereditary dermatoses, due to a keratinization disorder whose origin is still unclear; they could be due to the expansion of a clone of abnormal epidermal keratinocytes. Several clinical forms exist, of which the most common is disseminated superficial actinic porokeratosis; other forms include Mibelli, disseminated superficial, linear, palmoplantaris punctata and palmaris, plantaris et disseminata. These may coexist in the same patient or in different members of the same family. Porokeratoses manifest clinically with annular or linear, well-circumscribed keratotic plaques and share a common histological hallmark, the cornoid lamella, a vertical stack of parakeratotic corneocytes within the horny layer resting on a shallow depression of the underlying epidermis. Porokeratoses may be seen in the setting of various immunodeficiencies, namely in organ-transplant recipients, in whom the course of the disease may parallel the degree of immunosuppression. The overall prognosis of porokeratoses is favourable but is shadowed by the possibility of malignant transformation of the lesions (usually into squamous cell carcinoma); this happens in less than 10% of cases but may prove fatal. Although several surgical or medical (local or systemic) treatments have been tried, none of them has shown consistent and long-term efficacy. PMID- 25115204 TI - [Predicting chance of disease: calculation using prediction rules]. AB - A prediction rule is a statistical model that can be used to predict the presence or absence of a disease based on a limited number of tests or predictive factors. One of the mathematical methods used to formulate prediction rules is a logistic regression analysis of patient data. The discriminatory power of a model is visualizable using box-whisker plots and ROC curves; calibration plots show the match between the predicted chance and the observed frequency of a disease. These graphs are used to assess whether a model adequately reproduces reality. On publication of prediction rules it is important that the regression function is written out and that the chances of a disease on the basis of diagnostic scores are displayed in a histogram. For the practical significance of the model, it is also important to know how often the predicted low, medium or high probabilities of a disease do actually occur in comparison with the advance chance of occurrence. PMID- 25115202 TI - Genetic network identifies novel pathways contributing to atherosclerosis susceptibility in the innominate artery. AB - BACKGROUND: Atherosclerosis, the underlying cause of cardiovascular disease, results from both genetic and environmental factors. METHODS: In the current study we take a systems-based approach using weighted gene co-expression analysis to identify a candidate pathway of genes related to atherosclerosis. Bioinformatic analyses are performed to identify candidate genes and interactions and several novel genes are characterized using in-vitro studies. RESULTS: We identify 1 coexpression module associated with innominate artery atherosclerosis that is also enriched for inflammatory and macrophage gene signatures. Using a series of bioinformatics analysis, we further prioritize the genes in this pathway and identify Cd44 as a critical mediator of the atherosclerosis. We validate our predictions generated by the network analysis using Cd44 knockout mice. CONCLUSION: These results indicate that alterations in Cd44 expression mediate inflammation through a complex transcriptional network involving a number of previously uncharacterized genes. PMID- 25115205 TI - [Combination of exemestane and everolimus may produce toxic side effects: a new treatment option for metastatic hormone-sensitive breast cancer]. AB - The combination of exemestane and everolimus is a new treatment option for metastatic hormone-sensitive breast cancer. This treatment is used after progression on non-steroidal aromatase inhibitors. The treatment is generally well tolerated, but sometimes leads to minor or even serious side effects. It is important to be aware of these side effects and to treat them. We describe two patients who had to cope with various forms of toxicity: a 73-year-old woman with aphthous mouth lesions and a 49-year-old woman with pneumonitis. We then discuss the efficacy of the combination exemestane and everolimus and its positioning in the treatment of metastatic hormone-sensitive breast cancer. Finally, some common and some potentially serious side effects will be discussed, along with recommendations for their management and indications for distinguishing side effects from disease progression. PMID- 25115206 TI - [Hyperglycaemia during treatment with everolimus]. AB - BACKGROUND: Everolimus is an orally administered anti-cancer drug that inhibits the mammalian target of rapamycin (mTOR) signal transduction route. Use of everolimus may be associated with insulin resistance, manifesting in impaired glucose tolerance or hyperglycaemia. CASE DESCRIPTION: A 74-year-old female patient with a locally recurrent breast cancer developed hyperglycaemia, which started 2 weeks after the initiation of treatment with everolimus 10 mg once daily. Metformin and insulin were administered to restore normoglycaemia. CONCLUSION: At the initiation of treatment with an mTOR inhibitor such as everolimus the treating physician should be aware of the occurrence of hyperglycaemia. Metformin is then the medicine of first choice. PMID- 25115207 TI - [Glossopharyngeal neuralgia and syncope]. AB - BACKGROUND: The causes of neuralgia are usually not known, but the condition can be caused by an underlying condition. CASE DESCRIPTION: A 58-year-old man presented at the accident and emergency department with a 6-week history of continuous nagging pain in the region of his right ear, extending to the lower jaw and the right side of his neck; this worsened in progressive attacks, which were sometimes followed by non-rotatory dizziness and loss of consciousness. This clinical picture lead us to suspect glossopharyngeal neuralgia (GPN) because of the distribution of the pain and the secondary syncope, but the continuous nature of the pain was atypical and a reason for further investigation. This revealed metastatic parotid gland carcinoma with compression of the right glossopharyngeal nerve. Following palliative radiotherapy, the pain improved and there were no further episodes of loss of consciousness. CONCLUSION: When GPN is suspected and there is continuous pain, or neurological investigations reveal abnormalities, an underlying condition should be considered and additional investigations should be carried out. PMID- 25115208 TI - [The treatment of drooling in children]. AB - Undesirable drooling in children is an underexposed problem and difficult to treat, although there are multiple treatment options. A multidisciplinary approach is preferable for the examination and treatment of patients with drooling. The injection of botulinum toxin is the most frequently performed treatment for children who drool, but the effects are temporary. If drooling persists despite conservative treatment, surgical interventions performed by an otolaryngologist may be considered and may offer a more definitive solution. PMID- 25115209 TI - [Treatment of children with intestinal failure: intestinal rehabilitation, home parenteral nutrition or small intestine transplantation?]. AB - Intestinal failure is characterised by inadequate absorption of food or fluids, which is caused by insufficient bowel surface area or functioning. Children with chronic intestinal failure are dependent on parenteral nutrition (PN), which can be provided at home (HPN). In the Netherlands, HPN for children is coordinated by special HPN and intestinal failure teams from the Emma Children's Hospital, the Erasmus MC-Sophia Children's Hospital and the Radboud University Medical Center. HPN is the treatment of choice for children with chronic intestinal failure. Small intestine transplantation is only justified if HPN fails because complications arise; this procedure is carried out at the University Medical Center in Groningen. In addition to medical complications, HPN has psychosocial implications both for the children and their parents. Systematic attention to these can be provided by the 'Quality of Life in Clinical Practice' method, which also enables collection of data relevant for research purposes. PMID- 25115211 TI - [Thrombolysis not always necessary in patients with acute pulmonary embolism]. AB - International guidelines suggest that patients presenting with acute pulmonary embolism should be given routine thrombolysis on top of heparin. There is debate as to whether patients with acute pulmonary embolism who present in a haemodynamically stable condition, yet have signs of right ventricular dysfunction and increased troponin, actually need thrombolytic therapy. The results of the Pulmonary Embolism Thrombolysis study (PEITHO) show that in this particular patient group routine thrombolysis led to less haemodynamic decompensation or collapse, but that this advantage came with significantly higher incidences of haemorrhagic stroke and major extracranial bleeding. These results argue against routine thrombolysis in these patients. It is recommended that anticoagulation with heparin and vitamin K antagonists be given and patients be carefully monitored in hospital, particularly during the first three days. PMID- 25115212 TI - [Expensive new drugs for treating cancer: a dilemma]. AB - The number of new cancer patients in the Netherlands is increasing annually: there were approximately 100,000 new cases in 2010 and there will be more than 120,000 in 2020. The number of systemic therapies available for these patients is growing rapidly, and spending on anticancer drug doubled within ten years, to EUR 733 m in 2013. During the past few years the amount spent on new targeted drugs was compensated by the expiration of patents for frequently used cytostatics such as paclitaxel, docetaxel, gemcitabin, oxaliplatin and irinotecan. Immunotherapy is now available for patients with metastatic melanoma and the new 'checkpoint inhibitors' look promising for other cancers, including lung cancer, renal cell cancer, and bladder cancer. These drugs, as well as the numerous new targeted agents, are very expensive. The price for 4 cycles of ipilimumab for a patient with metastatic melanoma is approximately EUR 80,000. A special committee of the Dutch Cancer Society (KWF) released a report on the increasing costs of anticancer treatments and gave recommendations concerning how to address this issue. First of all, cost savings have to be achieved by lowering the price of the innovative drugs. The search for companion diagnostics should be encouraged, in order to avoid unnecessary drug administration. And, if these measures are not sufficient, the government should consider determining a price-ceiling for these treatments. A differentiation between treatments with curative intention or long term survival benefits and those which only have marginal effects, would appear to be logical. PMID- 25115213 TI - Value of clinical and laboratory inflammation factors in the postoperative period after laparoscopic urogynecological surgery. AB - BACKGROUND/AIMS: Leukocytes and C-reactive protein (CRP) levels are often used to detect infections. The aim of this study was to evaluate the diagnostic and screening validity of leukocytes and CRP levels as well as body temperature >38 degrees C to predict infections after laparoscopic sacrocolpopexy. METHODS: The study included 287 patients suffering from genital prolapse higher than POP-Q I. In addition to the sacrocolpopexy, a laparoscopic supracervical hysterectomy was performed in cases of preexisting uterus (n = 171). Leukocytes and CRP levels were analyzed preoperatively and 4 days after surgery. Early and late onset of infections was documented. RESULTS: Urinary tract infection was identified as the most frequent early postoperative complication (11.4%). Early wound infections were found in 2.8% of the patients (8/287). Late onset of infections was found in 1% of patients (3/287). Areas under ROC curves were low for both leukocytes (0.52, 95% CI: 0.37-0.66) and CRP levels (0.60, 95% CI: 0.44-0.77). CONCLUSION: Our findings question the benefit of routine determination of leukocytes and CRP levels 4 days after surgery. The sensitivity and specificity of leukocytes and CRP levels are probably more significant after normalization of the initial tissue response (days 8-10). PMID- 25115214 TI - Foreword. Pertussis vaccines. PMID- 25115215 TI - Impact of coronary artery disease on left ventricular ejection fraction recovery following transcatheter aortic valve implantation. AB - OBJECTIVES: The objective of the present study was to assess if the presence and severity of CAD is associated with decreased LVEF recovery after TAVI. BACKGROUND: Coronary artery disease (CAD) and low left ventricular ejection fraction (LVEF) are common findings in patients undergoing transcatheter aortic valve implantation (TAVI). The impact of CAD on LVEF recovery after TAVI has not been specifically evaluated. METHODS: All patients with LVEF<=50% who underwent TAVI between March 2006 and May 2012 were included in the study. The presence and severity of coronary artery disease was measured using the Duke Myocardial Jeopardy Score (DMJS). A DMJS = 0 corresponds to patients without CAD or complete revascularization and a DMJS > 0 to those with incomplete revascularization. LVEF recovery was assessed by transthoracic echocardiography, measuring the change in LVEF from baseline to 3-months post-TAVI. Myocardial viability was evaluated in a subgroup of patients using cardiac magnetic resonance (CMR) imaging pre-TAVI. RESULTS: Fifty-six patients were included in the study. Twenty-eight patients (50%) had a DMJS > 0. At 3 months, patients with incomplete revascularization (DMJS > 0) demonstrated less LVEF recovery post-TAVI (2.0 +/- 9.2% versus 11.7 +/ 8.9% if DMJS = 0; P = 0.001). On multivariate analysis, DMJS and presence of significant delayed-enhancement were found to be independent predictors of LVEF recovery. Patients with incomplete revascularization exhibited a worse prognosis with higher mortality at 30-days (22.2% versus 0% if DMJS = 0; P = 0.010) and 1 year (25.9% versus 3.5% if DMJS = 0; P = 0.019). CONCLUSIONS: The present study demonstrates an independent association between incomplete revascularization and decreased LVEF recovery in patients with left ventricular dysfunction undergoing TAVI for severe aortic stenosis. PMID- 25115217 TI - Complete penoscrotal transposition: case report and review of the literature. AB - Penoscrotal transposition is a rare congenital abnormality. We report a case presenting prenatally with ambiguous genitalia and renal anomaly on obstetric ultrasound and fetal MRI and discuss the postnatal examination and autopsy findings. We present a review of the literature, including associated gene abnormalities. PMID- 25115216 TI - Nitinol-based nanotubular coatings for the modulation of human vascular cell function. AB - In this study, we describe the synthesis of an upright nanotubular coating with discrete, exposed nanotubes on top of superelastic Nitinol via anodization and characterization of the surface elemental composition and nickel release rates. We demonstrate, for the first time, that this coating could improve re endothelialization by increasing the cell spreading and migration of primary human aortic endothelial cells on Nitinol. We also show the potential for reducing neointimal hyperplasia by decreasing the proliferation and expression of collagen I and MMP-2 in primary human aortic smooth muscle cells (HASMC). Furthermore, we did not observe the nanotubular surface to induce inflammation through ICAM-1 expression in HASMC as compared to the flat control. This coating could be used to improve Nitinol stents by reducing restenosis rates and, given the extensive use of Nitinol in other implantable devices, act as a generalized coating strategy for other medical devices. PMID- 25115218 TI - Barriers to employment of African American professionals in hospice: a qualitative study with African American social work students. AB - A major barrier to African American hospice utilization is the lack of African American hospice professionals. This qualitative study with 10 female African American social work students in a Midwestern university explored whether the participants were interested in hospice employment. Results provided information about reasons for the overall lack of diversity in hospice, reasons for the lack of African American staff in hospice, reasons for the lack of African American patients in hospice, and avenues toward knowledge about hospice by African American professionals. Barriers to African American employment included a lack of hospice content in social work education, differences between African American cultural and religious beliefs and hospice philosophy, and that the lack of African American hospice patients resulted in a lack of desire for employment in hospice. Strategies for recruiting and retaining African American hospice social workers are proposed. PMID- 25115219 TI - Enhancing the interaction between annexin-1 and formyl peptide receptors regulates microglial activation to protect neurons from ischemia-like injury. AB - As the immune cells of the brain, microglia are crucial for the maintenance of brain function. The aims of the present study were to determine whether and how annexin-1 is able to affect microglial phenotype and migration in the lesion microenvironment. In the current experiment, we enhanced the interaction between annexin-1 and formyl peptide receptors in microglia and analyzed the function. We found that annexin-1 could polarize microglia to a beneficial phenotype and promote microglial migration to protect neurons from ischemia-like injury, and the annexin-1-mediated neuroprotective effect was dependent on the release of glutamate and ATP from the injured neurons. PMID- 25115220 TI - Is physician awareness of impending death in hospital related to better communication and medical care? AB - BACKGROUND: In hospitals, where care is focused on cure and life prolongation, impending death is often recognized too late. Physician awareness of impending death is a prerequisite for communication with patients and relatives about dying in hospital and providing care that adequately addresses patients' needs. OBJECTIVE: To examine to what extent physicians are aware of the impending death of their dying patients and if awareness is related with communication and medical care, with quality of life in the last 3 days and quality of dying. DESIGN: Retrospective survey among hospital physicians after patient deaths. SETTING/SUBJECTS: Patients who died between June 2009 and February 2011 at Erasmus University Medical Center (Rotterdam, The Netherlands). MEASUREMENTS: Physician self-reported awareness of impending death, communication with patients and relatives, medical care, quality of life in the last 3 days, and quality of dying. RESULTS: The response rate was 44% (n=228). Physicians reported that they had been aware of the impending death in 67% of their dying patients. If they had been aware, discussing death with patients and relatives was more likely, as well as changing the treatment goal into comfort care or withholding treatment and prescribing opioids in the last 3 days of life. When physicians had been aware of impending death, they rated the quality of dying higher. CONCLUSIONS: In two thirds of deaths, hospital physicians had been aware of impending death of their dying patients. Physician awareness was related with more communication and more appropriate care in the last days of life. PMID- 25115221 TI - Levels of stigma among community mental health staff in Guangzhou, China. AB - BACKGROUND: Stigma and discrimination are widely experienced by people with mental illness, even in healthcare settings. The purposes of this study were to assess mental health stigma among community mental health staff in Guangzhou, China and in doing so also to assess the psychometric properties of the Reported and Intended Behaviour Scale (RIBS) - Chinese version. METHODS: A cross-sectional survey was undertaken among 214 community mental health staff in Guangzhou from September to November, 2013. The Mental Health Knowledge Schedule (MAKS) and RIBS were administered together with the Mental Illness: Clinicians' Attitudes Scale (MICA) to evaluate staff stigma from the perspective of knowledge, attitudes and behaviour. RESULTS: The total scores of RIBS, MAKS and MICA were (11.97 +/- 3.41), (16.80 +/- 5.39) and (51.69 +/- 6.94) respectively. Female staff members were more willing to contact people with mental illness than males (t(212) = 2.85,P = 0.005) and had more knowledge about mental illness (t(212) = -2.28,P = 0.024). The Chinese version of RIBS had good internal consistency (alpha = 0.82), test-retest reliability (r = 0.68,P < 0.001) and adequate convergent validity, as indicated by a significant negative correlation with the Chinese version of MICA(r = -0.43, P < 0.001). CONCLUSIONS: Our results show relatively high levels of stigma toward people with mental illness among community mental health staff in Guangzhou, China. There are slightly gender differences in discriminatory behaviours and stigma related knowledge of mental illness among community mental health staff, with female staff in general less stigmatising. Accordingly, anti stigma programmes should be established among healthcare staff. In addition, the Chinese version of RIBS is a reliable, valid and acceptable measure which can be used to assess the willingness of participants to contact people with mental illness in future anti-stigma campaigns. PMID- 25115223 TI - Tetramine poisoning in China: changes over a decade viewed through the media's eye. AB - BACKGROUND: Tetramine, or tetramethylenedisulfotetramine, is an internationally banned compound that had been used primarily as a rodenticide. Despite its regulatory status, there are widespread reports of its intentional use in human poisonings, primarily in China, and often in mass poisonings. Enhanced governmental regulations were implemented in 2003 to further reduce the availability of tetramine, though the effects of these regulations, and the current use of tetramine, remains unknown. METHODS: Reports from the website of the China News Agency were collected from 2000 to 2012. Details such as the location, date, and intent of the events were compared before and after the regulations were implemented. RESULTS: There were a total of 148 events during the study period (95 from 2000 to 2003, and 53 after 2003). There were a total of 3526 victims, including 225 fatalities. The majority of the events were homicidal/terroristic in nature. The incidence of events fell after 2006. More poisoning events occurred in central China, such as Henan and Jiangsu province, and an increase was noted in April and September. CONCLUSION: Tetramine poisoning events, as reported in the national Chinese media, fell after the implementation of strict regulation on tetramine. The causal relationship is not known. PMID- 25115222 TI - Pelger-Huet anomaly in a cat. AB - A 14-year-old, spayed female Domestic Shorthair cat was referred to the Purdue University Veterinary Teaching Hospital (PUVTH) for iodine 131 treatment of hyperthyroidism. Upon arrival, a biochemistry profile and a CBC were performed. Approximately 50% of the neutrophils and all the eosinophils observed were hyposegmented with a mature, condensed chromatin pattern. Nuclei had a band to "dumbbell" shape, and rarely a round shape, suggesting a Pelger-Huet anomaly or a pseudo Pelger-Huet. Based on both a negative FeLV and FIV tests, the absence of any clinical signs to support an inflammatory process, and the persistence of this granulocytic morphology 6 months after its previous admission to the PUVTH, a diagnosis of Pelger-Huet anomaly was established in this cat. PMID- 25115224 TI - Narcotics anonymous: a comparison of military veterans and non-veterans. AB - Substance use disorder, which is often comorbid with post-traumatic stress disorder (PTSD), is a problem confronted by many veterans. To determine the potential utility of Narcotics Anonymous (NA) for veterans, 508 NA attendees were studied. Veterans (n = 172) were more likely to have been referred by a professional than were non-veterans (77% vs. 27%, respectively); 70% had been hospitalized for alcohol or drug problems, and 51% had been treated for non substance psychological problems. The 70% of veterans who reported at least 1 of 3 service-related stressful experiences were more likely to report PTSD-related symptoms. NA can serve as a recovery resource for certain veterans with substance use disorders, with or without PTSD. PMID- 25115225 TI - Left atrial metastasis of renal cell carcinoma: a case report and review of the literature. AB - BACKGROUND: Cardiac metastasis of renal cell carcinoma is an exceptional event, particularly when there is lack of inferior vena cava involvement. Indeed, only a few cases have been reported worldwide thus far. Moreover, discussion of treatment and follow-up strategies for cardiac metastasis of renal cell carcinoma is important because of the high risk of sudden death. CASE PRESENTATION: We report the case of a 75-year-old Japanese man with metastatic tumor in the left atrium from renal cell carcinoma. He had a history of right renal cell carcinoma, for which he had undergone hand-assisted laparoscopic nephrectomy. Lung and bone metastases were detected after nephrectomy, and treatment with interferon-alpha was initiated. After disease progression, he was treated concurrently with targeted molecular therapy and radiotherapy for bone metastasis. After these therapies, a 42 * 24 mm mass was found on transthoracic echocardiography in left atrium without involvement of the right atrium or inferior vena cava. The provisional diagnosis was metastatic mass or myxoma, and surgical resection was performed. Histopathological examination led to a final diagnosis of metastatic tumor from clear cell renal cell carcinoma. CONCLUSION: Cardiac metastasis, metastasis to the left atrium in particular, is rare in patients with renal cell carcinoma. In our study, surgery of the cardiac mass was effective to avoid sudden death and quality of life decline resulting from heart failure. We describe this case and review cardiac metastasis of renal cell carcinoma. PMID- 25115226 TI - Influence of genetic factors on the ephedrine alkaloid composition ratio of Ephedra plants. AB - We investigated the ephedrine alkaloid [(-)-ephedrine and (+)-pseudoephedrine] composition ratio of a crude Chinese herbal drug described in the Japanese Pharmacopoeia 'Ephedra herb (Chinese name: Mahuang)'. There were marked changes in the alkaloid composition ratio of wild plants in areas where both male and female clusters coexisted. However, in genetically homogeneous areas with the growth of male or female clusters alone, all of the coefficients of the regression lines were positive, but each gradient varied. This suggests that the alkaloid composition ratio has a clear tendency in each individual. Based on this, we cultivated individuals for vegetative propagation, and evaluated the alkaloid content ratio. Those propagated by separating the roots showed a specific tendency regardless of the cultivation area (Wakayama, Tanegashima). Those propagated by separating the herbaceous stem showed a specific tendency regardless of the soil or harvest time. In addition, we surveyed the (-) ephedrine content ratio of 3- to 6-year-old strains. There was a high positive correlation coefficient between the previous and subsequent years. These findings suggest that the ephedrine alkaloid composition ratio of Ephedra herb depends on genetic factors, but not on environmental factors or the growth period. PMID- 25115227 TI - Identification of marker compounds for Japanese Pharmacopoeia non-conforming jujube seeds from Myanmar. AB - Jujube seed is a crude drug defined as the seed of Ziziphus jujuba Miller var. spinosa Hu ex H.F. Chou (Rhamnaceae) in the Japanese Pharmacopoeia (JP). Most of the jujube seed in the Japanese markets is imported from China, with the rest obtained from other Asian countries. Here we confirmed the botanical origins of jujube seeds from both China and Myanmar by a DNA sequencing analysis. We found that the botanical origins of the crude drugs from China and Myanmar were Z. jujuba and Z. mauritiana, respectively. Although the jujube seed from China conforms to the JP, that from Myanmar does not. A method for discriminating jujube seeds from China and Myanmar using a chemical approach is thus desirable, and here we sought to identify a compound specific to Z. jujuba. Jujuboside A (1) was identified as a compound specific to Z. jujuba. To establish a purity test of Jujube Seed in the JP against Z. mauritiana, we fractionated the extract of Z. mauritiana seeds and identified frangufoline (2) and oleanolic acid (4) as the marker compounds specific to Z. mauritiana. Thin-layer chromatography (TLC) and gas chromatography-mass spectrometry analyses revealed that the latter compound was useful for testing by TLC analysis. The established TLC conditions were as follows: chromatographic support, silica gel; developing solvent, n hexane:EtOAc:HCOOH = 10:5:1; developing length, 7 cm; visualization, diluted sulfuric acid; R f value, 0.43 (oleanolic acid). PMID- 25115228 TI - FERTILITY INTENTIONS AND EARLY LIFE HEALTH STRESS AMONG WOMEN IN EIGHT INDIAN CITIES: TESTING THE REPRODUCTIVE ACCELERATION HYPOTHESIS. AB - In life history theory, early life adversity is associated with an accelerated reproductive tempo. In harsh and unpredictable conditions in developing societies fertility is generally higher and the reproductive tempo faster than in more secure environments. This paper examines whether differences in female anthropometry, particularly adult height, are associated with fertility intentions of women in urban environments in India. The study population consists of women aged 15-29 (N=4485) in slums and non-slums of eight Indian cities in the National Family Health Survey (NFHS) of 2005-2006. Adult height is taken as a proxy for early childhood health and nutritional condition. Fertility intentions are examined by using two variables: the desire to have a child or another child, and to have it relatively soon, as indicative of accelerated reproductive scheduling. Evidence supporting the acceleration hypothesis is found in two urban frames out of 26 examined in a two-staged multinomial logistic model. In three cases, the relationship between fertility intentions and height is the opposite than expected by the acceleration hypothesis: taller women have a higher predictive probability of desiring a(nother) child and/or narrower birth spacing. Potential explanations for the partly contradictory relationship between the childhood health indicator and fertility intentions are discussed. PMID- 25115231 TI - Experience using a rapid assay for aneuploidy and microdeletion/microduplication detection in over 2,900 prenatal specimens. AB - BACKGROUND: While microarray testing can identify chromosomal abnormalities missed by karyotyping, its prenatal use is often avoided in low-risk pregnancies due to the possible identification of variants of uncertain significance (VOUS). METHODS: We tested 2,970 prenatal samples of all referral indications using a rapid BACs-on-Beads-based assay with probes for sex chromosomes, common autosomal aneuploidies, and 20 microdeletion/microduplication syndromes, designed as an alternative to microarray in low-risk pregnancies and an alternative to rapid aneuploidy testing in pregnancies also undergoing microarray analysis. RESULTS: Interpretable results were obtained in 2,940 cases (99.0%), with 89% receiving results in 1 day. Aneuploidies were detected in 7.3% and partial chromosome abnormalities in 0.45% (n = 13), including 5 referred for maternal age, abnormal maternal serum screen, or isolated ultrasound markers. The added detection above karyotype was 1 in 745 in lower-risk cases with normal ultrasounds or isolated ultrasound markers/increased nuchal measurements and 1 in 165 for fetuses with structural/growth abnormalities. Neither false negatives nor false positives were found within test limitations. Female polyploidy could not be detected, while polyploidies with Y chromosomes were suspected and confirmed through additional analysis. CONCLUSION: When combined with karyotyping, this assay provides increased interrogation of specific chromosomal regions, while limiting VOUS identification. PMID- 25115230 TI - Clinical evaluation of resin-based composites in posterior restorations: a 3-year study. AB - OBJECTIVES: The aim of this study was to evaluate the clinical performance of a nanohybrid and a microhybrid composite in class I and II restorations after 3 years. SUBJECTS AND METHODS: A total of 82 class I and class II restorations were performed in 31 patients (10 males and 21 females) using Grandio and QuiXfil with self-etch adhesives (Futurabond and Xeno III). The restorations were clinically evaluated by 2 operators 1 week after placement (baseline) and at 6 months and 1, 2, and 3 years using modified United States Public Health Service (USPHS) criteria. At the 3-year follow-up, 62 class I and class II cavities were reevaluated in 23 patients (7 males and 16 females). Statistical analysis was performed using Pearson's chi(2) and Fisher's exact tests (p < 0.05). RESULTS: At the 6-month follow-up, all restorations received Alfa scores with respect to each evaluation criterion. At the 1-year follow-up, 2 QuiXfil restorations had to be replaced and Grandio restorations started to deteriorate in terms of marginal adaptation. At the end of 2 years, 9 Grandio restorations showed significant deterioration of the surface properties, demonstrating Bravo scores. At the end of 3 years, no significant differences were observed regarding color match, marginal adaptation, secondary caries, marginal discoloration, and anatomic form loss between the evaluated materials in 25 class I and 37 class II restorations. At the 3-year follow-up, Grandio restorations had 21% Bravo scores and showed significant deterioration of the surface properties, which were still clinically acceptable according to USPHS criteria. Three QuiXfil and 1 Grandio restorations were replaced because of secondary caries and loss of retention. CONCLUSIONS: Both the nanohybrid (Grandio) and the microhybrid (QuiXfil) composites were clinically functional after 3 years. PMID- 25115232 TI - Systematic review of proximal femoral arthroplasty for non-neoplastic conditions. AB - Proximal femoral arthroplasty (PFA) is an established treatment modality following oncological resection. Increasingly, these prostheses are being used for non-neoplastic conditions such as fractures and bone loss associated with septic or aseptic loosening. We performed a systematic review of the literature to determine the failure rates, mortality rates and hip outcome scores when PFAs were used in non-neoplastic conditions. There were 14 studies with an average follow-up of 3.8 years (range 0-14 years) describing 356 PFAs. Re-operation for any reason occurred in 23.8% (85/356) of cases. The most common complications were dislocation (15.7%) and infection (7.6%). The mortality rate ranged from 0% to 40%. PFA provides an acceptable surgical solution when confronted with massive bone loss, but it has a high re-operation rate for dislocation and infection. PMID- 25115233 TI - RDOS-family: a guided learning tool for layperson assessment of respiratory distress. PMID- 25115235 TI - Locked tension band wiring using ring pins for patellar fractures: a method of minimising implant migration. AB - BACKGROUND: A modified K-wire attached with ring (ring pin) was used to treat a displaced patellar fracture, and the ring pin was locked with tension band wiring. The purpose of this study was to evaluate the surgical outcome of this method with respect to its procedural safety. METHODS: The authors retrospectively reviewed 36 patients treated for a displaced patellar fracture and assessed bone union, fixation failure, postoperative pain, range of motion, and incidence of hardware removal. Clinical outcome was evaluated using the Bostman scoring system. The mean follow-up period was 27 (range 13-47) months. RESULTS: Bony union was achieved in all patients. No fixation failure and pin migration were detected. Hardware was removed in three cases (8.3 %). Reasons for removal were pain in one case and vague discomfort in two cases. The average Bostman scores at 12 months postoperatively were 29.6, with 34 (94.4 %) patients graded as excellent. The average active flexion of the knee joint was 130.4 degrees (range 125 degrees -150 degrees ), with an average flexion contracture of 3 degrees (range 0 degrees -10 degrees ). CONCLUSIONS: This implant could facilitate satisfactory fixation, restore the integrity of the extensor mechanism, and reduce the possibility of implant migration and implant-related discomfort. PMID- 25115234 TI - The risk of second primary malignancy is increased in differentiated thyroid cancer patients with a cumulative (131)I dose over 37 GBq. AB - BACKGROUND: The aim of this study was to investigate the risk factors for second primary malignancy (SPM) diagnosed after differentiated thyroid cancer (DTC). METHODS: A total of 2468 DTC patients who underwent thyroidectomy were reviewed. SPM was defined as a non-thyroidal malignancy, diagnosed at least 1 year after the diagnosis of thyroid cancer. Patients were divided into five groups according to cumulative (131)I dose: very high-activity (>= 37.0 GBq), high-activity (22.3 36.9 GBq), intermediate-activity (5.56-22.2 GBq), low-activity (1.1-5.55 GBq) and no RAI. RESULTS: Among the 2468 patients, 61 (2.5%) had SPMs during 7.0 (1.0 33.0) years of median follow-up. Age above 40 years, male sex and very high activity RAI were independent risk factors for the development of SPM. SPM related mortality was highest in the very high-activity group, while DTC-related mortality was highest in the high-activity group. The overall mortality both from SPM and DTC was highest in the high-activity group. CONCLUSION: A cumulative (131)I dose <37.0 GBq did not increase the risk of SPM. A cumulative (131) I dose >= 37.0 GBq increased the risk of SPM and SPM-related mortality and decreased the DTC-specific mortality, resulting in a similar all-cause mortality compared with the low-activity RAI group. Using repeated high-dose RAI for treating RAI responsive but persistent DTC patients needs careful consideration of the individual benefits from RAI vs the risk of developing SPM. PMID- 25115236 TI - Diffusion and diversion of suboxone: an exploration of illicit street opioid selling. AB - Interviews with fourteen opioid retail pill sellers provides an exploration into the diversion and diffusion of Suboxone to recreational ("week-end warriors") drug users. The use of social media and electronic devices enables the diffusion of Suboxone to dependent and non-dependent opiate/opioid drug abusers. Overprescribing by physicians and prescribing in drug treatment settings fuels the diversion of Suboxone. The diversion and the diffusion of Suboxone have the potential to delay entrance into drug treatment and promote the misuse of the drug by both dependent opiate/opioid drug abusers and recreational users. The dilemma posed by Suboxone maintenance treatment will not be easily addressed or mitigated in the near future. PMID- 25115238 TI - Unmet needs in the treatment of psoriasis. AB - Biologics have greatly improved the treatment of moderate-to-severe plaque psoriasis, as most patients are now able to achieve an initial improvement of 75% in the Psoriasis Area and Severity Index. However, only ~20%-57% reach a 90% improvement in this measurement and responses may be lost over time. In addition, there are potential safety issues as TNF-inhibitor biologics have been associated with infections or non-melanoma skin malignancies. Here we review unmet needs with current therapies for psoriasis. We researched the medical literature to discuss new therapies in development and assess their potential to meet these needs. Several new classes of anti-psoriatic drugs are currently undergoing clinical development and potential improvements with these new therapies include attaining earlier and higher-level responses that are durable, more specific targeting of cytokines involved directly in psoriatic inflammation, and new therapies offering convenient administration. Additionally, based on results from clinical trials evaluating these new agents, it may be possible to find predictive markers that identify patients best treated with certain drug classes, those prone to lose treatment responses and patients who can discontinue treatment and remain in remission. It remains to be determined whether the promising results seen in early studies of therapies in development for psoriasis will translate into actual improvements over currently available treatment options. PMID- 25115237 TI - Brachyury cooperates with Wnt/beta-catenin signalling to elicit primitive-streak like behaviour in differentiating mouse embryonic stem cells. AB - BACKGROUND: The formation of the primitive streak is the first visible sign of gastrulation, the process by which the three germ layers are formed from a single epithelium during early development. Embryonic stem cells (ESCs) provide a good system for understanding the molecular and cellular events associated with these processes. Previous work, both in embryos and in culture, has shown how converging signals from both nodal/TGFbetaR and Wnt/beta-catenin signalling pathways specify cells to adopt a primitive-streak-like fate and direct them to undertake an epithelial-to-mesenchymal transition (EMT). However, many of these approaches have relied on genetic analyses without taking into account the temporal progression of events within single cells. In addition, it is still unclear to what extent events in the embryo are able to be reproduced in culture. RESULTS: Here, we combine flow cytometry and a quantitative live single-cell imaging approach to demonstrate how the controlled differentiation of mouse ESCs towards a primitive streak fate in culture results in cells displaying many of the characteristics observed during early mouse development including transient brachyury expression, EMT and increased motility. We also find that the EMT initiates the process, and this is both fuelled and terminated by the action of brachyury, whose expression is dependent on the EMT and beta-catenin activity. CONCLUSIONS: As a consequence of our analysis, we propose that a major output of brachyury expression is in controlling the velocity of the cells that are transiting out of the primitive streak. PMID- 25115240 TI - Melomics music medicine (M3) to lessen pain perception during pediatric prick test procedure. PMID- 25115239 TI - Retrospective observational study of diagnostic accuracy of the Xpert(r) MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis. AB - BACKGROUND: Fiberoptic bronchoscopy (FOB) is a useful diagnosis tool in low burden countries for patients with suspected pulmonary tuberculosis (TB) who are smear-negative or sputum-scarce. This study sought to determine the accuracy of the Xpert(r) MTB/RIF (XP) assay using FOB samples. METHODS: We retrospectively reviewed clinical, radiological, and microbiological characteristics of 175 TB suspected patients requiring diagnostic FOB (bronchial aspirate or bronchoalveolar lavage) with XP assay. Polymerase chain reaction (PCR) and smear microscopy (SM) performances were first compared to culture, then to the final diagnosis, established based on clinical or radiological evolution when cultures were negative. RESULTS: Of the total 162 included patients, 30 (18.5%) had a final diagnosis of pulmonary TB, with positive cultures reported in 23. As compared to culture, sensitivity and specificity values were 80.0% and 98.6% for the XP assay, and 25.0% and 95.8% for SM, respectively. As compared to final diagnosis, the corresponding performance values were 60.0% and 100.0% for the XP assay, and 16.7% and 95.5% for SM, respectively. The sensitivity of the XP assay was significantly higher than that of SM in both cases (p=0.003 and p=0.001). Concerning the final diagnosis, both XP assay and culture sensitivities were similar (60% vs. 66.7%). PCR assay enabled pulmonary TB to be diagnosed earlier in 13 more cases, compared to SM. CONCLUSION: Our study has confirmed the clinical benefits provided by XP assay compared to SM for the early diagnosis of suspected pulmonary TB cases requiring FOB, on per procedure samples, especially in a low TB-burden country. PMID- 25115241 TI - Selective-area epitaxy of pure wurtzite InP nanowires: high quantum efficiency and room-temperature lasing. AB - We report the growth of stacking-fault-free and taper-free wurtzite InP nanowires with diameters ranging from 80 to 600 nm using selective-area metal-organic vapor phase epitaxy and experimentally determine a quantum efficiency of ~50%, which is on par with InP epilayers. We also demonstrate room-temperature, photonic mode lasing from these nanowires. Their excellent structural and optical quality opens up new possibilities for both fundamental quantum optics and optoelectronic devices. PMID- 25115242 TI - Conjugative transfer of ICESde3396 between three beta-hemolytic streptococcal species. AB - BACKGROUND: Integrative conjugative elements (ICEs) are mobile genetic elements (MGEs) that possess all genes necessary for excision, transfer and integration into recipient genome. They also carry accessory genes that impart new phenotypic features to recipient strains. ICEs therefore play an important role in genomic plasticity and population structure. We previously characterised ICESde3396, the first ICE identified in the beta-hemolytic Streptococcus dysgalactiae subsp equisimilis (SDSE) and demonstrated its transfer to single isolates of Streptococcus pyogenes (group A streptococcus, GAS) and Streptococcus agalactiae (group B streptococcus, GBS). While molecular studies found the ICE in multiple SDSE and GBS isolates, it was absent in all GAS isolates examined. RESULTS: Here we demonstrate that ICESde3396:km is transferable from SDSE to multiple SDSE, GAS and GBS isolates. However not all strains of these species were successful recipients under the same growth conditions. To address the role that host factors may have in conjugation we also undertook conjugation experiments in the presence of A549 epithelial cells and DMEM. While Horizontal Gene Transfer (HGT) occurred, conjugation efficiencies were no greater than when similar experiments were conducted in DMEM. Additionally transfer to GAS NS235 was successful in the presence of DMEM but not in Todd Hewitt Broth suggesting that nutritional factors may also influence HGT. The GAS and GBS transconjugants produced in this study are also able to act as donors of the ICE. CONCLUSION: We conclude that ICEs are major sources of interspecies HGT between beta-hemolytic streptococci, and by introducing accessory genes imparting novel phenotypic characteristics, have the potential to alter the population structure of these species. PMID- 25115243 TI - Antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children and adolescents: a systematic review protocol. AB - BACKGROUND: Abacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases. METHODS: We plan to do a systematic review to evaluate the antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children aged between 3 months and 18 years, compared with other NRTIs. We will search Scopus, Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science databases for eligible studies regardless of language or publication status. We will check the reference lists of included studies, search relevant conference proceedings, email the authors of included studies and also look for unpublished and ongoing trials in prospective clinical trial registries. Two authors will independently screen search outputs, select studies, extract data and assess the risk of bias in included studies. All disagreements will be resolved by discussion and consensus. Where data allow, we will conduct meta-analysis for similar types of participants, study designs, interventions, and outcome measures. If the results are statistically homogeneous, we will use the fixed effect model; otherwise, we will use the random-effects model and explore the reasons for heterogeneity using subgroup analyses. Heterogeneity will be assessed with the Chi-squared test and quantified with the I-squared statistic. DISCUSSION: The findings will be useful to policy makers and programme managers to inform treatment and management of HIV in children and adolescents and to point out research gaps for future research. TRIAL REGISTRATION: This review is registered with PROSPERO, registration number CRD42014009157. PMID- 25115244 TI - Microvolt T-wave alternans profile in patients with pulmonary arterial hypertension. PMID- 25115245 TI - Personalized CHF treatment: PCT to guide therapy in heart failure patients. AB - Sorting out the etiology of dyspnea in patients with a history of heart failure is not always straightforward. Although an acute heart failure exacerbation would seem to be easy to distinguish from an acute respiratory illness, data from objective clinical studies has shown otherwise. Procalcitonin (PCT), a biomarker that rises in the setting of bacterial infection, carries great potential for guiding the diagnosis and treatment of heart failure patients with possible acute respiratory infection. In this issue of the International Journal of Cardiology, Kutz et al. demonstrated that patients with a history of heart failure and suspected lower respiratory tract infection experienced reduced antibiotic duration and superior outcomes with PCT-guided therapy. The results in this subset of heart failure patients from the ProHOSP study were consistent with the results seen in the overall study population. This study points to the need for a randomized controlled trial in a broader population of heart failure patients with acute dyspnea, to further define the prominent role that PCT can play in more personalized medical treatments that can improve patient outcomes. PMID- 25115246 TI - Effects of OX40-OX40 ligand interaction on the levels of ROS and Cyclophilin A in C57BL/6J mice atherogenesis. AB - BACKGROUND: An increasing amount of evidence shows that the OX40-OX40L interaction serves an important function in atherosclerosis. However, the mechanism of the OX40 signaling pathway remains unclear. This study investigates the effect of OX40-OX40L interaction on the levels of intracellular reactive oxygen species (ROS) and the secretion of Cyclophilin A (CyPA) in C57BL/6J mice atherogenesis. METHODS: The atherosclerotic plaque model was established by placing a rapid perivascular carotid collar on C57BL/6J mice fed with a western type diet. In vivo, the expressions of CyPA in mouse plaque and lymphocytes were detected by immunohistochemical and Western blot analyses, respectively. In vitro, the expression of CyPA protein in cultured lymphocytes of C57BL/6J mice was assessed by using Western blot analysis. The level of ROS was detected through flow cytometry. RESULTS: CyPA expression was significantly increased in the atherosclerotic lesions and lymphocytes from C57BL/6J mice. The ROS levels in OX40(+)-lymphocytes were increased in vitro and in vivo. After stimulating the OX40-OX40L interaction, the ROS and CyPA levels in lymphocytes were obviously increased in vitro, whereas anti-OX40L mAb significantly down-regulated the anti OX40 mAb-induced ROS generation and inhibited CyPA secretion in lymphocytes. CONCLUSION: The OX40-OX40L interaction up-regulates intracellular levels of ROS in C57BL/6J mice and increases CyPA secretion in lymphocytes. Increased CyPA secretion may serve an important function in atherosclerotic plaque formation. PMID- 25115247 TI - The value of CHADS2 score in predicting new-onset atrial fibrillation in Chinese patients with acute myocardial infarction. PMID- 25115248 TI - Bioabsorbable stent thrombosis Quo Vadis: is Kounis syndrome still present? PMID- 25115249 TI - Albumin may prevent hypertension by inhibiting renin angiotensin aldosterone system. PMID- 25115250 TI - Maternal NT-proBNP in chronic hypertensive pregnancies and superimposed preeclampsia. PMID- 25115251 TI - QRS fragmentation and epsilon waves in Fontaine leads in arrhythmogenic right ventricular cardiomyopathy: re: "The use of fontaine leads in the diagnosis of arrhythmogenic right ventricular dysplasia" and "Arrhythmogenic right ventricular cardiomyopathy: contribution of different electrocardiographic techniques". PMID- 25115252 TI - Out-of-hospital versus in-hospital Takotsubo cardiomyopathy: analysis of 3719 patients in the Diagnosis Procedure Combination database in Japan. AB - BACKGROUND: Although Takotsubo cardiomyopathy (TC) generally occurs after a stressful event out-of-hospital, it occasionally occurs secondary to acute medical illness after hospital admission. No study has examined and compared patient backgrounds and in-hospital outcomes between patients with out-of hospital TC and those with in-hospital TC. METHODS AND RESULTS: Using the Diagnosis Procedure Combination inpatient database in Japan, we identified 3719 eligible patients with a diagnosis of TC who underwent coronary angiography without any revascularization procedure between 2010 and 2013, including 419 patients with in-hospital TC and 3300 patients with out-of-hospital TC. There was no significant difference in age between those with in-hospital TC and those with out-of-hospital TC (74.2 +/- 10.9 years versus 73.4 +/- 11.3 years, p=0.211). Patients with in-hospital TC had a higher proportion of males than out-of hospital TC patients (31.3% versus 21.3%, p<0.001). Patients with in-hospital TC had significantly higher proportions of several chronic comorbidities and acute medical illnesses. In-hospital mortality was significantly higher in patients with in-hospital TC than in patients with out-of-hospital TC (17.9% versus 5.4%, p<0.001). In the multivariable logistic regression analysis, in-hospital TC was significantly associated with higher in-hospital mortality (adjusted odds ratio 2.02; 95% confidence interval, 1.43 to 2.85; p<0.001), even after adjustment for patient backgrounds. Malignancy, chronic liver disease, rheumatic disease, sepsis, pneumonia, cerebrovascular diseases, acute renal failure, and acute gastrointestinal diseases were also significantly associated with higher in hospital mortality. CONCLUSIONS: In-hospital TC was associated with more severe clinical background and poorer short-term prognosis than out-of-hospital TC. PMID- 25115253 TI - Evaluation of the clinical use of midregional pro-atrial natriuretic peptide (MR proANP) in comparison to N-terminal pro-B-type natriuretic peptide (NT-proBNP) for risk stratification in patients with light-chain amyloidosis. PMID- 25115254 TI - The relationship between epicardial fat thickness and arterial stiffness; role of antihypertensive drugs and statins. PMID- 25115255 TI - Renal denervation: does prior renal stenting really matter? PMID- 25115257 TI - Air pollution and the risk of stroke by meta-analysis. PMID- 25115256 TI - Extreme bradycardia associated with nebivolol therapy. PMID- 25115258 TI - Rates of aldosterone antagonist use after myocardial infarction remain poor over time among guideline eligible patients. PMID- 25115259 TI - Ambulatory blood pressure may be designed as the primary efficacy outcome in clinical trials on renal denervation. PMID- 25115260 TI - Reversible attenuation of the amplitude of the electrocardiogram QRS complexes in a patient with Takotsubo syndrome: a quantitative analysis. PMID- 25115261 TI - Fibrinolysis in intermediate risk pulmonary embolism: too much risk for too little reward? PMID- 25115262 TI - Blood pressure components and stroke in Inner Mongolians--a prospective cohort study. PMID- 25115263 TI - Elevated concentrations of high-density lipoprotein cholesterol and cardiovascular risk paradox in patients with coronary heart disease and the equivalents. PMID- 25115265 TI - FGF23 and risk of all-cause mortality and cardiovascular events: a meta-analysis of prospective cohort studies. PMID- 25115264 TI - Coronary artery fistula: comparison of diagnostic accuracy by echocardiography versus coronary arteriography and surgery in 63 patients studied between 2002 and 2012 in a single medical center in China. AB - BACKGROUND: Coronary artery fistula (CAF) is a rare congenital anomaly, which is conventionally diagnosed by coronary arteriography; however, the relation of the coronary artery fistulas to other structures, their origin and course may not be always apparent. METHODS: The echocardiograms of 63 patients with coronary artery fistulas, who had undergone coronary arteriography and/or surgery from June 2002 to December 2012 at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, were analyzed retrospectively, and the results were compared with findings by coronary arteriography and at surgery. RESULTS: Right CAFs were detected in 33 of the 63 patients (52.4%); 11 had drainage to the right atrium, 10 to the right ventricle, 2 to the left ventricle, 9 to the main pulmonary artery, and 1 to the coronary sinus. Left CAFs were detected in 29 patients (46.0%); 6 had drainage to the right atrium, 12 to the right ventricle, 1 to the left atrium, 2 to the left ventricle, 7 to the main pulmonary artery, and 1 to the coronary sinus. One patient (1.6%) had the origin of the fistula in both coronary arteries. The entry point of the fistula was most often a single orifice (96.8%) and rarely multi-orificial (3.2%). 57 patients (90.5%) had isolated coronary fistulas (90.5%); 6 patients (9.5%) had other congenital cardiac malformations. The ultrasonic diagnosis of 60 patients was in line with findings at surgery and/or coronary arteriography. The diagnostic accuracy rate for coronary artery fistula was 95.2%. Preoperative transthoracic echocardiography missed the diagnosis of coronary artery fistula in three patients (4.8%). There is no difference (P>0.05) in diagnostic accuracy between echocardiography and coronary arteriography and/or surgery. CONCLUSIONS: Transthoracic echocardiography, in comparison with coronary arteriography and/or surgery, is much simpler, easier, less expensive, safer, readily repeatable, and more convenient with equal accuracy, and should be the first-line method for the diagnosis of congenital coronary artery fistula. PMID- 25115266 TI - Comparison of pooled cohort risk equations and Framingham risk score for metabolic syndrome in a Korean community-based population. PMID- 25115267 TI - Pitavastatin decreases serum LOX-1 ligand levels and MT1-MMP expression in CD14 positive mononuclear cells in hypercholesterolemic patients. PMID- 25115268 TI - Non-culprit coronary vasospasm in a woman affected by Churg-Strauss syndrome presenting with ST-elevation myocardial infarction. PMID- 25115269 TI - SYNTAX-score based assessment of appropriate candidates for percutaneous coronary intervention among patients with chronic total occlusion. PMID- 25115270 TI - Multiplane spectroscopic whole-body photoacoustic imaging of small animals in vivo. AB - We have successfully developed a multiscale acoustic-resolution photoacoustic tomography system in a single imaging platform. By switching between ultrasound transducers (center frequencies 5 and 40 MHz) and optical condensers, we have photoacoustically imaged microvasculatures of small animals in vivo at different scales. Further, we have extended the field of view of our imaging system to entire bodies of small animals. At different imaging planes, we have noninvasively imaged the major blood vessels (e.g., descending aorta, intercostal vessels, cephalic vessels, brachial vessels, femoral vessels, popliteal vessels, lateral marginal vessels, cranial mesenteric vessels, mammalian vessels, carotid artery, jugular vein, subclavian vessels, iliac vessels, and caudal vessels) as well as intact internal organs (e.g., spleen, liver, kidney, intestine, cecum, and spinal cord) of the animals in vivo. The spectroscopic whole-body photoacoustic imaging clearly reveals the spectral responses of the internal structures. Similar to other existing preclinical whole-body imaging systems, this whole-body photoacoustic tomography can be a useful tool for small-animal research. PMID- 25115271 TI - Perceptions and attitudes of pharmacy students towards volunteering at health promotional programs: a cross-sectional study from Malaysia. AB - The present study aims to explore the perceptions and understanding of future pharmacists towards volunteerism in health promotional activities. The study was designed as a cross sectional, descriptive survey. All pharmacy undergraduates (n = 293) from the first, second and third professional years enrolled at the School of Pharmaceutical Sciences, Universiti Sains Malaysia were targeted for the study. A pre validated, 15-itemed questionnaire was used for data collection and was analysed by using SPSS. Dichotomous groups were compared with Mann-Whitney U test. The Jonckheere-Terpstra test was used to evaluate the trend of association. Where significant associations were reported, effect size was calculated by using Kendall tau correlation coefficient. p value of <0.05 was considered to be of statistical significance. Out of 200 respondents, 185 completed the study with a response rate of 92.5 %. Agreement with mandatory status of volunteerism at community services was significant with gender (p = 0.003) and year of study (p = 0.045). Confidence in performing health promotional activities (p = 0.001, tau = 0.155) and needed communication skills during health promotional activities (p = 0.022, tau = 0.322) were also significantly associated with year of study with a moderate positive trend from junior to senior classes. Although pharmacy undergraduates showed positive interest and will to volunteer at the health promotional programs, certain issues were also highlighted. Therefore, in order to address these challenges, pharmacy curriculum needs to include a greater emphasis on role of pharmacists in public health. This can be achieved by having a dedicated core course as part of pharmacy curriculum. PMID- 25115272 TI - Spontaneous Nephrocutaneous Fistula: A Case Report, Update of the Literature and Management Algorithm. AB - AIMS: Spontaneous nephrocutaneous fistula (NCF) is a rare and severe condition. The aim of this study was to update the data of the literature about this disease and, reporting and considering also our experience in 1 case of NCF, to make a new clinical algorithm. METHODS: This study was done with a review of all the literature and a comparison with our experience. RESULTS: The characteristic sign of spontaneous NCF is a flank sinus discharging material. Physical examination and computed tomography usually lead to the diagnosis. The main predisposing factors are renal stones/staghorn calculi, xanthogranulomatous pyelonephritis and renal tuberculosis. In the vast majority of the cases kidneys are poorly functioning or nonfunctioning. Surgical approach is the common management and usually consists of open nephrectomy. We create a clinical management algorithm obtained by a review of the literature and our experience with spontaneous NCF. CONCLUSIONS: Spontaneous NCF represents a very serious renal disease leading to loss of the kidney in the vast majority of cases. We propose a revised and user friendly clinical diagnostic-therapeutic algorithm for spontaneous NCF based on the worldwide literature. PMID- 25115274 TI - Cancer survivorship and palliative care? PMID- 25115273 TI - Maternal organ donation and acute injuries in surviving children. AB - PURPOSE: The purpose of this study is to test whether maternal deceased organ donation is associated with rates of subsequent acute injuries among surviving children after their mother's death. METHODS: This is a longitudinal cohort analysis of children linked to mothers who died of a catastrophic brain event in Ontario, Canada, between April 1988 and March 2012. Surviving children were distinguished by whether their mother was an organ donor after death. The primary outcome was an acute injury event in surviving children during the year after their mother's death. RESULTS: Surviving children (n=454) had a total of 293 injury events during the year after their mother's death, equivalent to an average of 65 events per 100 children per year and a significant difference comparing children of mothers who were organ donors to children of mothers who were not organ donors (21 vs 82, P<.001). This difference in subsequent injury rates between groups was equal to a 76% relative reduction in risk (95% confidence interval, 62%-85%). CONCLUSIONS: Deceased organ donation was associated with a reduction in excess acute injuries among surviving children after their mother's death. An awareness of this positive association provides some reassurance about deceased organ donation programs. PMID- 25115275 TI - Reproductive pattern of Cuban women living in the municipality of Plaza de la Revolucion, Havana, Cuba. AB - This paper assesses the reproductive and abortion patterns of women living in Plaza de la Revolucion, a municipality of Havana, Cuba, by studying the factors influencing birth and abortion rates. Socio-demographic data and female reproductive histories were collected in a survey of 1200 post-menopausal women living in the municipality. Average ages at menarche and at menopause were 12.71 and 48.39 years, respectively, thus yielding a potential long reproductive period of 35.68 years, indicating high fertility. Although the mean pregnancy rate was 3.81 pregnancies per woman, the live birth rate at time of delivery was only 1.89 due to the high rate of abortions: 40% of all pregnancies were voluntarily interrupted. Among the biological and socio-cultural variables that were found to influence the rate of live births were those related marriage pattern, especially age at first union. Demographic variables such as pregnancy order, maternal age and marital status were the main determinants of the abortion pattern, with abortion being used as a method of birth control in order to obtain the desired family size, and most women (75.2%) using contraceptives. PMID- 25115276 TI - Better late than never: the perceived benefits of smoking cessation among women in late midlife. AB - The current study examined the association of smoking cessation (>=1 year without relapse) and self-reported psychosocial and physical outcomes among a community sample of women (N = 195; mean age = 63.7 years, SD = 5.7 years). Data were collected in 1985-1986 and 2009. Successful smoking cessation for >=1 year was significantly associated with each of the outcome measures (e.g., less financial stress [adjusted odds ratio (AOR) = 0.50; 95% confidence interval (CI) = 0.25 1.00, P< 0.05), less life dissatisfaction (AOR = 0.51, 95% CI = 0.24-1.09, P< 0.05). Findings suggest that older women should be included in smoking cessation programs, and the important benefits of quitting should be used to encourage cessation. PMID- 25115277 TI - The impact of maternal obesity, age, pre-eclampsia and insulin dependent diabetes on severe maternal morbidity by mode of delivery-a register-based cohort study. AB - PURPOSE: To determine the rate of severe maternal morbidity related to delivery by delivery mode and to assess if the impact of studied risk factors varies by delivery mode. METHODS: A register-based study including all women having singleton delivery in Finland in 2007-2011, n = 292,253, data derived from the Finnish Medical Birth Registry and Hospital Discharge Registry. Diagnoses and interventions indicating a severe maternal complication were searched and the mode of delivery was assessed by data linkage. The impact of obesity, maternal age 35 years or more, pre-eclampsia and insulin dependent diabetes on severe maternal morbidity (all severe complications, severe infections and severe) was studied in each mode of delivery and calculated as Odds ratios. RESULTS: The overall incidence of severe complications was 12.8/1,000 deliveries. The total complication rate was lowest in vaginal deliveries (VD) in all risk groups. Obesity increased the risk for all severe complications and severe infections in the total population, but not significantly in specific delivery modes. Age increased the risk of hemorrhage in VD. Pre-eclampsia increased the risk for hemorrhage in all deliveries except elective CS. In women with pre-eclampsia, overall morbidity was similar in VD, attempted VD and elective CS. The presence of any studied risk factor increased the risk for complications within the risk groups by the high proportion of emergency CS performed. CONCLUSIONS: An attempt of VD is the safest way to deliver even for high-risk women with the exception of women with pre-eclampsia, who had a similar risk in an attempt of VD and elective CS. PMID- 25115278 TI - Anti-tumour activity of phosphoinositide-3-kinase antagonist AEZS-126 in models of ovarian cancer. AB - PURPOSE: Platinum resistance is the most crucial problem for treatment of ovarian cancer. There is a clinical need for new treatment strategies which overcome platinum resistance. Recently high level of AKT was shown to be involved in platinum resistance and furthermore in resistance against Natural-killer (NK) cell mediated killing in ovarian cancer. METHODS: Here, we investigate the ability of the PI3K/AKT inhibitor AEZS-126 alone and in combination with rapamycin to selectively target ovarian cancer cell proliferation and survival in vitro by MTT-assays and FACS based analysis. Furthermore the mechanism of cytotoxicity is analysed by FACS based assays. The NK-killing efficiency of ovarian cancer cells with and without pre-treatment with AEZS-126 was analysed. RESULTS: AEZS-126 showed good anti-tumour activity in in vitro models of ovarian cancer. Main mechanism of cytotoxicity seems to be necroptosis which could be abrogated by co-incubation with necrostatin-1. Furthermore pre-treatment of platinum resistant cells with AEZS-126 resulted in an increased accessibility of these tumour cells for killing by NK-cells. CONCLUSION: We demonstrated the highly efficient anti-tumour activity of AEZS-126 in in vitro models of ovarian cancer. Due to the good anti-tumour activity and the expected increase in NK-cell mediated killing even of platinum resistant tumour cells, AEZS-126 seems to be a promising candidate for clinical testing in ovarian cancer. PMID- 25115279 TI - Slow-freezing versus vitrification for human ovarian tissue cryopreservation. AB - PURPOSE: Ovarian tissue can be cryopreserved prior to chemotherapy using either the slow-freezing or the vitrification method; however, the data on the equality of the procedures are still conflicting. In this study, a comparison of the cryo damage of human ovarian tissue induced by either vitrification or slow-freezing was performed. METHODS: Ovarian tissue from 23 pre-menopausal patients was cryopreserved with either slow-freezing or vitrification. After thawing/warming, the tissue was histologically and immunohistochemically analyzed and cultured in vitro. During tissue culture the estradiol release was assessed. RESULTS: No significant difference was found in the proportion of high-quality follicles after thawing/warming in the slow-freezing and vitrification group, respectively (72.7 versus 66.7 %, p = 0.733). Estradiol secretion by the ovarian tissue was similar between groups during 18 days in vitro culture (area-under-the-curve 5,411 versus 13,102, p = 0.11). Addition of Sphingosine-1-Phosphate or Activin A to the culture medium did not alter estradiol release in both groups. The proportion of Activated Caspase-3 or 'Proliferating-Cell-Nuclear-Antigen' positive follicles at the end of the culture period was similar between slow freezing and vitrification. CONCLUSION(S): Slow-freezing and vitrification result in similar morphological integrity after cryopreservation, a similar estradiol release in culture, and similar rates of follicular proliferation and apoptosis after culture. PMID- 25115280 TI - Molecular analysis of miscarriage products using multiplex ligation-dependent probe amplification (MLPA): alternative to conventional karyotype analysis. AB - PURPOSE: The present study aims to evaluate whether multiplex ligation-dependent probe amplification (MLPA) technique with subtelomeric probes is to be an alternative method of routine G-banding chromosome analysis from pregnancy loss. METHODS: A review of 5 years (from 2005 to 2009) of karyotype for products of conception (POCs) was carried out. From June 2010 to June 2012, MLPA was performed in parallel with karyotype analysis on 347 miscarriages. Karyotyped miscarriages served as controls in this blinded study. Abnormal results were confirmed by fluorescence in situ hybridization. RESULTS: A review of 5 years of karyotype results for POCs indicated that 11.46 % of cases failed to karyotyping. In the study periods, MLPA results were successfully obtained from all cases including 51 (14.7 %) culture failed cases, chromosomal abnormalities were detected in 27 (52.9 %) of cases which failed to grow or could not be cultivated. It took 3 weeks by conventional karyotyping, but it required at least 24 h and at most a week by MLPA from tissue sampling to final reporting. 47 cases showed discordant results between karyotyping and MLPA because of maternal cell contamination, polyploidy, mosaicism, or balanced translocation. CONCLUSIONS: MLPA technique is relatively low cost, less labor intensive and reduces waiting time with high accuracy compared with conventional cytogenetic analysis. Therefore, MLPA can be the first approach for chromosome analysis from pregnancy loss. PMID- 25115281 TI - Cotyledonoid dissecting leiomyoma of the uterus: report of two cases. AB - BACKGROUND: Cotyledonoid dissecting leiomyoma (Sternberg tumor) is a rare variant of the uterine smooth muscle tumor. Although this tumor is a benign tumor clinically and pathologically, the appearance and growth pattern is unusual, so it may be misdiagnosed as malignancy. CASE REPORTS: We report two cases of cotyledonoid dissecting leiomyoma of the uterus that occurred in two 44- and 31 year-old women, respectively. Total hysterectomy and bilateral salpingo oophorectomy were performed in one of the patients, and myomectomy was done in the other one. Macroscopically, both tumors were grape-like exophytic masses resembling placental tissue. The patients were well after surgery, and one patient gave birth. To our knowledge, this is the first case report of a successful delivery after myomectomy of this tumor. CONCLUSION: To prevent aggressive surgery it is important to recognize that this tumor is a benign and unusual appearing variant of leiomyoma. A fertility-sparing surgical procedure should be considered if the patient wishes to preserve her fertility. PMID- 25115282 TI - Stage IIIC endometrial cancer: the need for novel subgrouping according to the ratio of metastatic lymph nodes. AB - INTRODUCTION: The survival rates in endometrial cancer (EC) patients with lymph node (LN) metastasis vary greatly. Many other factors may have impact on the prognosis within this special group. The purpose of this study was to determine factors predicting the progression or death in patients with stage IIIC EC. MATERIALS AND METHODS: A single tertiary center, retrospective analysis was conducted in a total of 38 consecutive patients who surgically treated for EC between January 2005 and January 2013. The primary endpoint was the determination of factors predicting the progression, recurrence, or death of any cause. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: The median age at diagnosis was 64 years, and the median follow-up time was 32.50 months (95 % CI 28.75-40.56). The median number of metastatic positive LNs (pelvic and/or paraaortic) was 2, and the LN ratio, expressed as the percentage of positive nodes to total LNs identified, was 6.3 %. The LN ratio (>= 6.5 %) was the only independent parameter for progression or death in multiple logistic regression analysis. Patients were stratified according to the LN ratio (<6.5 vs. >= 6.5 %) for survival comparisons. The estimated 32-month PFS rates were 90 and 64.8 %, respectively [HR (95 % CI) = 5.07 (1.05-24.56), P = 0.025]. However, the estimated 32-month OS rates were comparable (94.1 vs. 94.1 %), [HR (95 % CI) = 4.26 (0.44-41.30), P = 0.21]. DISCUSSION: The stratification of patients with stage IIIC disease according to the LN ratio may allow better identification of prognostic information and selection of individualized patient tailored adjuvant treatment modalities. PMID- 25115284 TI - Integrated computational materials discovery of silver doped tin sulfide as a thermoelectric material. AB - Accelerating the discovery of new materials is crucial for realizing the vision of need-driven materials development. In the present study we employ an integrated computational and experimental approach to search for new thermoelectric materials. High-throughput first principles calculations of thermoelectric transport coefficients are used to screen sulfide compounds conforming to the boundary conditions of abundant and innocuous components. A further computational screening step of substitutional defects is introduced, whereby SnS doped with monovalent cations is identified as having favorable transport properties. By silver doping of SnS under S-rich conditions an electric conductivity more than an order of magnitude higher than reported previously is realized. The obtained thermoelectric power-factor at room temperature is comparable to the state of the art for thermoelectric materials based on earth abundant, non-toxic elements. The high-throughput screening of extrinsic defects solves a long standing bottleneck in search of new thermoelectric materials. We show how the intrinsic carrier concentration in the low-temperature phase of SnSe is two orders of magnitude higher than in SnS. We furthermore find that the carrier concentration in SnSe can still be further optimized by silver doping. PMID- 25115283 TI - Comparative studies using the Morris water maze to assess spatial memory deficits in two transgenic mouse models of Alzheimer's disease. AB - Evaluation of the efficacy of novel therapeutics for potential treatment of Alzheimer's disease (AD) requires an animal model that develops age-related cognitive deficits reproducibly between independent groups of investigators. Herein we assessed comparative temporal changes in spatial memory function in two commercially available transgenic mouse models of AD using the Morris water maze (MWM), incorporating both visible and hidden platform training. Individual cohorts of cDNA-based 'line 85'-derived double-transgenic mice coexpressing the 'Swedish' mutation of amyloid precursor protein (APPSwe) and the presenillin 1 (PS1) 'dE9' mutation were assessed in the MWM at mean ages of 3.6, 9.3 and 14.8 months. We found significant deficits in spatial memory retention in APPSwe/PS1dE9 mice aged 3.6 months and robust deficits in spatial memory acquisition and retention in APPSwe/PS1dE9 mice aged 9.3 months, with a further significant decline by age 14.8 months. beta-Amyloid deposits were present in brain sections by 7.25 months of age. In contrast, MWM studies with individual cohorts (aged 4-21 months) of single-transgenic genomic-based APPSwe mice expressing APPSwe on a yeast artificial chromosomal (YAC) construct showed no significant deficits in spatial memory acquisition until 21 months of age. There were no significant deficits in spatial memory retention up to 21 months of age and beta-amyloid deposits were not present in brain sections up to 24 months of age. These data, generated using comprehensive study designs, show that APPSwe/PS1dE9 but not APPSwe YAC mice appear to provide a suitably robust model of AD for efficacy assessment of novel AD treatments in development. PMID- 25115285 TI - In vivo assessment of the effect of a cream containing Avena Rhealba((r)) extract and hyaluronic acid on the restoration of the skin barrier in de-epidermised skin produced with an erbium-YAG laser. AB - Wound healing studies require standardised methods for evaluating wounding and skin repair. Our study aimed to demonstrate the suitability of the erbium-YAG (Er YAG) laser method to produce reliable epidermal lesions for evaluation of different skin repair creams. Skin de-epidermised by Er-YAG laser (four uniform epidermal ablations, area 8 * 8mm, in 21 healthy subjects) was treated with a product (A) containing Avena Rhealba((r)) extract and hyaluronic acid and assessed for epidermal regeneration and barrier restoration. This treatment was compared to two reference products (B) and (C) and an untreated control. Over 22 days of treatment, double-blind measurements of wound characteristics were made for instrumental (wound surface area, barrier restoration, 3D skin topography) and clinical evaluation (lesion quality and tolerance). Tested product (A) resulted in a shorter time (9 days) and faster rate of wound closure than product C (12 days) and the untreated zone (16 days). Results for products (A) and (B) were similar. Clinical evaluation of lesion quality showed the same trends as the wound area/closure parameter. Barrier recovery assessments revealed that all three products showed a similar rate of decreasing Transepidermal Water Loss (TEWL), which was significantly faster than the rate for the control. In conclusion, the laser-induced epidermal wound model provided standardised lesions, enabling discrimination between different topical skin repair products. PMID- 25115287 TI - Length scaling of carbon nanotube electric and photo diodes down to sub-50 nm. AB - Carbon nanotubes (CNTs) are promising candidates for future optoelectronics and logic circuits.1-3 Sub-10 nm channel length CNT transistors have been demonstrated with superb performance.4 Yet, the scaling of CNT p-n diodes or photodiodes, basic elements for most optoelectronic devices, is held back on a scale of micrometers.5-8 Here, we demonstrate that CNT diodes fabricated via a dopant-free technique show good rectifying characteristics and photovoltaic response even when the channel length is scaled to sub-50 nm. By making a trade off between performance and size, a diode with both channel length and contact width around 100 nm, fabricated on a CNT with a small diameter (d ~ 1.2 nm), shows a photovoltage of 0.24 V and a fill factor of up to 60%. Study on the dependence of turn-on voltage on scaled channel length reveals transferred charges induced potential barrier at the contact in long channel diodes and the effect of self-adjusting charge distribution. This effect could be utilized for realizing stable and high performance sub-100 nm pitch CNT diodes. As elementary building blocks, such tiny electric and photodiodes could be used in nanoscale rectifiers, photodetectors, light sources, and high-efficiency photovoltaic devices. PMID- 25115286 TI - Determinants of outcome of solitary fibrous tumors of the pleura: an observational cohort study. AB - BACKGROUND: Solitary fibrous tumors of the pleura (SFTP) are rare and their long term outcome is difficult to predict, as there are insufficient data which allow accurate characterization of the malignant variant. Thus the aim of this study was to describe the outcome and possible determinants of malignant behavior of SFTPs. METHODS: Data were collected retrospectively from medical records of patients treated at the University Hospital Zurich from 1992 to 2012. Kaplan Meier and Cox regression analysis were performed to define disease-free survival time (defined as survival without tumor-recurrence or tumor-related death) using the classical histo-morphological criteria (tumor size, localization, pedunculation, tumor necrosis or hemorrhage, mitotic activity and nuclear pleomorphism) and immunohistochemical parameters. RESULTS: 42 patients (20 males) with SFTP (median (IQR) age 62 (56-71) years) could be identified. SFTP were associated with symptoms in 50% of all cases. Complete resection was achieved by video-assisted thoracic surgery or thoracotomy in 20 and 22 patients, respectively. Three SFTP-related deaths (7.1%) and four tumor recurrences (9.5%) were observed. Mean disease-free survival time was 136.2 (+/- 13.1) months, and 2 , 5- and 10-year disease-free survival was 91%, 84%, and 67%, respectively. Mean disease-free survival inversely correlated with the mean tumor diameter, number of mitotic figures and proliferation rate (Ki-67 expression). Other criteria (tumor necrosis, atypical localization, sessile tumor, and pleomorphism) were not statistically significant prognostic parameters. CONCLUSIONS: Patients with large SFTP with a high mitotic index and high proliferation rate should be followed-up closely and over a prolonged time period in order to recognize recurrence of the SFTP early and at a treatable stage. Future research on this topic should focus on the prognostic role of immunohistochemistry including Ki-67 expression and molecular parameters. PMID- 25115288 TI - Characterization of 19 new microsatellite loci for the Omani barb Garra barreimiae from 454 sequences. AB - BACKGROUND: Garra barreimiae is a cyprinid fish from the southeastern Arabian Peninsula, which inhabits regularly desiccating wadis and survives in isolated ponds or underground. In 1984 a cave-dwelling population was found in the Al Hoota cave system and previous genetic analyses revealed some differentiation with limited gene flow between the surface populations and the cave population. Since no suitable markers are available for evaluation of gene flow between the cave population and the adjacent surface populations, we focused on designing and establishing novel microsatellite markers from next generation sequencing data. FINDINGS: 19 microsatellite markers containing di- and tetranucleotide simple sequence repeats were developed from 454 sequences. Forty-four individuals from two surface populations (Wadi Al Falahi and Misfat Al Abriyeen) of G. barreimiae (sampling permission number 13/2012, export permission number 29/2012) were used for analyses and characterization of the loci. On average, the number of alleles per locus is 7.6 (range: 2-20). Two markers displayed indication of linkage disequilibrium in both populations (DL6X, 9XNC). Significant deviation from Hardy Weinberg equilibrium was observed at four loci in the Misfat Al Abriyeen population (2PUM, 88CM, 1EHE, 3Z7M) and at two loci in the Wadi Al Falahi population (QLIM, 3 N43). Three of the microsatellite loci were significant for null alleles in one of the two populations (Misfat Al Abriyeen: CJHG; Wadi Al Falahi: PH8A, 3ROZ). Expected and observed heterozygosities ranged from 0 to 95.0% respectively from 0 to 95.8% (Wadi Al Falahi) and from 0 to 89.1% respectively from 0 to 95.0% (Misfat Al Abriyeen). Fourteen of these markers were successfully cross-amplified in G. rufa. CONCLUSION: This 19 microsatellite loci provide a useful tool to understand the structure and genetic differences of populations. Moreover, these markers will help to evaluate species delimitation in G. barreimiae and potentially even in related species. PMID- 25115290 TI - Ethnic Minority Status and Body Image Dissatisfaction: A Scoping Review of the Child and Adolescent Literature. AB - To systematically summarize the literature examining ethnic minority status and body image dissatisfaction (BID) among children and adolescents living in Canada and the United States. Literature was identified by entering search terms into six electronic databases and through an electronic hand search of key research journals. Eligible sources were those published between 1946 and November 2012, conducted within Canada or the United States, included ethnic minority children or adolescents (<19 years), and measured BID through self-report. Synthesis of the sources followed the principles of thematic and content analysis (Vaismoradi et al. in Nurs Health Sci 15:398-405, 2013). A total of 33 sources were included in our scoping synthesis; spanning from 1991 to 2011. No results emerged from Canada. Evidence from the United States is equivocal. The literature is plagued by inconsistent nomenclature and inadequate attention to issues of measurement, sex and gender. A more robust evidence-base requires advanced methods to examine the intersection of ethnicity, sex and gender on BID among children and adolescents. PMID- 25115291 TI - The Impact of Healthcare Access on Knowledge and Willingness for HIV Testing in Chinese Female Entertainment Workers. AB - Chinese female entertainment workers are at high risk for HIV. We assessed the impact of healthcare access on HIV knowledge, condom use, and their willingness to receive HIV testing. We surveyed 257 entertainment workers in a cross sectional study. Demographic, knowledge, and behavioral risk factors were examined. Of 257 women, 107 (42.1%) reported inconsistent condom use. Only 9% had prior HIV testing. Their HIV knowledge was generally poor. Having access to healthcare, being able to obtain condoms, and managers providing health information were associated with consistent condom use (all P < 0.01). Having access to healthcare was related to previous HIV testing (P < 0.01). Our study showed that having a doctor and access to healthcare had positive effects on HIV knowledge and likelihood of condom use and previous HIV testing. Chinese medical providers can play a significant role in encouraging HIV testing and outreach in migrant women employed at entertainment venues. PMID- 25115292 TI - Extrusion of the medial meniscus in knee osteoarthritis assessed with a rotating clino-orthostatic permanent-magnet MRI scanner. AB - PURPOSE: The objectives of this study were to assess the influence of weight bearing on tibiofemoral osteoarthritis, including medial meniscal extrusion, by using a low-field (0.25 T) rotating clino-orthostatic permanent-magnet magnetic resonance (MR) scanner, and to analyse correlations of medial meniscal extrusion with the patient's Kellgren-Lawrence score, body mass index, and all the osteoarthritis features of the WORMS scoring system. MATERIALS AND METHODS: Twenty-six patients (69.2% women and 30.8% men; mean age 67 +/- 9.7 years) with medial tibiofemoral knee osteoarthritis were prospectively enrolled and MR sequences were acquired in both clino- and orthostatic position. MR images were assessed by two independent radiologists, according to the WORMS scale. Medial meniscal extrusion was measured and its clino-orthostatic difference (?MME) was calculated. RESULTS: Intra- and inter-observer agreement of the WORMS Global Score readings was high by Cohen's K test (>0.81). No significant clino orthostatic changes in the scoring parameters of the medial tibiofemoral joint were shown by Wilcoxon's test. Medial meniscal extrusion measured on orthostatic images was significantly higher than that measured in clinostatic position (p < 0.0001). At univariate analysis, the Kellgren-Lawrence score, WORMS Global Score, cartilage loss, meniscal damage, and osteophytes were significantly correlated to ?MME (p < 0.005). Using a multiple regression model, tibiofemoral cartilage loss was found to correlate independently with ?MME (p = 0.0499). CONCLUSIONS: Medial meniscal extrusion, evaluated with an open-configuration, rotating MR scanner, increased from the clinostatic to the orthostatic position. ?MME, a new meniscal parameter, correlated with several important features of medial tibiofemoral osteoarthritis. PMID- 25115289 TI - Seeing the forests and the trees--innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol. AB - BACKGROUND: To improve quality of care and patient outcomes, health system decision-makers need to identify and implement effective interventions. An increasing number of systematic reviews document the effects of quality improvement programs to assist decision-makers in developing new initiatives. However, limitations in the reporting of primary studies and current meta analysis methods (including approaches for exploring heterogeneity) reduce the utility of existing syntheses for health system decision-makers. This study will explore the role of innovative meta-analysis approaches and the added value of enriched and updated data for increasing the utility of systematic reviews of complex interventions. METHODS/DESIGN: We will use the dataset from our recent systematic review of 142 randomized trials of diabetes quality improvement programs to evaluate novel approaches for exploring heterogeneity. These will include exploratory methods, such as multivariate meta-regression analyses and all-subsets combinatorial meta-analysis. We will then update our systematic review to include new trials and enrich the dataset by surveying authors of all included trials. In doing so, we will explore the impact of variables not, reported in previous publications, such as details of study context, on the effectiveness of the intervention. We will use innovative analytical methods on the enriched and updated dataset to identify key success factors in the implementation of quality improvement interventions for diabetes. Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results. DISCUSSION: This study will inform future systematic reviews of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta-analysis. It will also result in an updated comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42013005165. PMID- 25115293 TI - Nuclear medicine and the emergency department patient: an illustrative case-based approach. AB - Radiologists are familiar with the use of radiographs, computed tomography, magnetic resonance imaging and ultrasound in the acute clinical setting. However, there are some specific clinical scenarios which may be found in nuclear medicine imaging problem-solving tools. These clinical scenarios and imaging techniques are less frequent, and the referring clinician from the emergency department may not consider these alternatives. It is important for the radiologist to be aware of these techniques to be able to guide the clinician to use those tools, which may result in optimal patient care. In this article, we will discuss those nuclear medicine studies which have application in the setting of an emergency radiology practice. PMID- 25115294 TI - Diaphragmatic injuries: why do we struggle to detect them? AB - Diaphragmatic injury is an uncommon traumatic condition. It can be easily missed due to a lack of awareness by both clinicians and radiologists. A high index of suspicion is required for the establishment of an early diagnosis and prevention of life-threatening complications. Multidetector computed tomography (MDCT) is the modality of choice for the detection of diaphragmatic injury. In this review article, we illustrate the MDCT appearance of blunt and penetrating diaphragmatic injuries and emphasize the role of the emergency radiologist in detecting these entities. PMID- 25115296 TI - Our experience with retroperitoneal laparoendoscopic single-site ureterolithotomy. AB - AIM: To report our experience with retroperitoneal laparoendoscopic single-site (LESS) ureterolithotomy for the management of large proximal ureteral stones. PATIENTS AND METHODS: From July 2011 to April 2012, 20 patients underwent retroperitoneal LESS ureterolithotomy. The indications for the operation were impacted upper ureteral stones larger than 15 mm. A reusable elastic single-port device with 3 working channels was inserted through the 2.5-cm incision at the midpoint between the costal arch and iliac crest on the mid-axillary line. A rigid 10-mm 30 degrees extra-long laparoscope was introduced for monitoring, and a combination of lengthened pre-bent and conventional laparoscopic instruments was used for handling. The surgical procedure was similar to conventional retroperitoneal laparoscopic ureterolithotomy. RESULTS: Retroperitoneal LESS ureterolithotomy was completed in all of the patients. The mean stone size was 18.8 mm (range 16-28). The mean operative time was 108 min (range 75-140). Significant bleeding was not observed, and no major intraoperative complications occurred in any of the patients. The mean hospital stay was 4.4 days (range 3-7). CONCLUSIONS: Retroperitoneal LESS ureterolithotomy, using a reusable elastic single-port device, is technically feasible and safe, and the combination of conventional and pre-bent laparoscopic instruments represents an attractive option for retroperitoneal LESS. PMID- 25115297 TI - Soluble CD138/Syndecan-1 Increases in the Sera of Patients with Moderately Differentiated Bladder Cancer. AB - BACKGROUND: CD138/Syndecan-1 (Sdc-1) is expressed on the tumor and stromal cells of invasive bladder carcinoma. CD138/Sdc-1 shedding from the cell surface is associated with the invasive phenotype in lung and breast cancers. PATIENTS AND METHODS: Soluble CD138/Sdc-1 was measured in the sera of 86 bladder cancer patients and 57 healthy individuals by a commercial ELISA assay. RESULTS: Soluble Sdc-1 was increased in the sera of patients with bladder cancer (138.42 +/- 81.85 vs. 86.48 +/- 82.58 ng/ml, p = 0.0003). Patients aged over 70 years had higher levels of CD138/Sdc-1 in their sera (159.7 +/- 15.77 vs. 124.5 +/- 9.99 ng/ml, p = 0.025), and soluble Sdc-1 levels were higher in the sera of patients with moderately differentiated tumors compared to poorly differentiated ones (170.47 +/- 85.06 vs. 101.79 +/- 68.24 ng/ml, p = 0.01). The soluble Sdc-1 level was higher in muscle-invasive (154.45 +/- 83.60 vs. 89.9 +/- 55.02 ng/ml) but not lymphatic-invasive (106.25 +/- 52.10 vs. 123.43 +/- 63.76 ng/ml) tumors (p = 0.027 and 0.45, respectively). A non-significant trend of soluble Sdc-1 increase in the sera of male patients compared to female patients was observed (145.38 +/- 85.47 vs. 110.20 +/- 59.04 ng/ml, p = 0.054). CONCLUSION: The elevated levels of soluble CD138/Sdc-1 in older bladder cancer patients and those with muscular invasion sheds some light on the mechanisms of the disease invasion. PMID- 25115298 TI - EFA6B antagonizes breast cancer. AB - One of the earliest events in epithelial carcinogenesis is the dissolution of tight junctions and cell polarity signals that are essential for normal epithelial barrier function. Here, we report that EFA6B, a guanine nucleotide exchange factor for the Ras superfamily protein Arf6 that helps assemble and stabilize tight junction, is required to maintain apico-basal cell polarity and mesenchymal phenotypes in mammary epithelial cells. In organotypic three dimensional cell cultures, endogenous levels of EFA6B were critical to determine epithelial-mesenchymal status. EFA6B downregulation correlated with a mesenchymal phenotype and ectopic expression of EFA6B hampered TGFbeta-induced epithelial-to mesenchymal transition (EMT). Transcriptomic and immunohistochemical analyses of human breast tumors revealed that the reduced expression of EFA6B was associated with loss of tight junction components and with increased signatures of EMT, cancer stemness, and poor prognosis. Accordingly, tumors with low levels of EFA6B were enriched in the aggressive triple-negative and claudin-low breast cancer subtypes. Our results identify EFA6B as a novel antagonist in breast cancer and they point to its regulatory and signaling pathways as rational therapeutic targets in aggressive forms of this disease. PMID- 25115299 TI - GBV-C infection and risk of NHL among U.S. adults. AB - Some retrospective studies suggest an association between infection with GB virus C (GBV-C) and non-Hodgkin lymphoma (NHL). We evaluated this association prospectively in a nested case-control study within the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Cases (N = 658) and controls (N = 1,316) were individually matched by age, sex, race/ethnicity, timing of study entry, and sample selection. Prediagnostic PLCO serum samples were tested for GBV-C RNA (as a measure of active infection) and E2 antibody (active or resolved infection). Logistic regression was used to estimate odds ratios (OR) for the association between GBV-C and NHL overall and NHL subtypes. Twelve cases (1.8%) and seven controls (0.5%) were GBV-C RNA-positive. GBV-C RNA positivity was associated with NHL overall [OR, 3.43; 95% confidence interval (CI), 1.35-8.71] and, based on small numbers, diffuse large B-cell lymphoma (OR, 5.31; 95% CI, 1.54-18.36). The association with NHL persisted when the interval between testing and selection was greater than 4 years (OR, 6.00; 95% CI, 1.21 29.73). In contrast, E2 antibody positivity was not associated with NHL risk (OR, 1.08; 95% CI, 0.74-1.58). Our study demonstrates that GBV-C infection precedes development of NHL. GBV-C infection may play an etiologic role in a small proportion of NHL cases, perhaps by causing chronic immune stimulation or impaired immunosurveillance. PMID- 25115295 TI - Bowel intussusceptions in adults: the role of imaging. AB - Intestinal intussusception in adults is a rare condition, accounting for about 0.003-0.02% of all hospital admissions. This condition in adults represents only 5% of all cases of intussusceptions and is different from paediatric intussusception, which is usually idiopathic. In contrast, almost 90% of cases in adults are secondary to various pathologies that serve as a lead point, such as polyps, Meckel's diverticulum, colonic diverticulum, or malignant or benign neoplasm. The aim of the present study was to assess the capabilities of multislice computed tomography (MSCT) in the diagnosis and correct characterisation of intussusception, especially in distinguishing between intussusceptions with a lead point and those without. Indeed, although the MSCT findings that help to differentiate between lead point and non-lead point intussusceptions have not been well studied, abdominal MSCT remains the most sensitive radiological tool to confirm bowel intussusceptions. Moreover, differentiating intussusceptions with a lead point condition from those without is crucial for directing the patient towards the most appropriate treatment, avoiding surgery when not necessary. PMID- 25115302 TI - Defining "serious illness". PMID- 25115301 TI - Gangliosides drive the tumor infiltration and function of myeloid-derived suppressor cells. AB - Although it is now widely appreciated that antitumor immunity is critical to impede tumor growth and progression, there remain significant gaps in knowledge about the mechanisms used by tumors to escape immune control. In tumor cells, we hypothesized that one mechanism of immune escape used by tumors involves the synthesis and extracellular shedding of gangliosides, a class of biologically active cell surface glycosphingolipids with known immunosuppressive properties. In this study, we report that tumor cells engineered to be ganglioside deficient exhibit impaired tumorigenicity, supporting a link between ganglioside-dependent immune escape and tumor outgrowth. Notably, we documented a dramatic reduction in the numbers and function of tumor-infiltrating myeloid-derived suppressor cells (MDSC) in ganglioside-deficient tumors, in contrast with the large MDSC infiltrates seen in ganglioside-rich littermate control tumors. Transient ganglioside reconstitution of the tumor cell inoculum was sufficient to increase MDSC infiltration, supporting a direct connection between ganglioside production by tumor cells and the recruitment of immunosuppressive MDSC into the tumor microenvironment. Our results reveal a novel mechanism of immune escape that supports tumor growth, with broad implications given that many human tumors produce and shed high levels of gangliosides. PMID- 25115300 TI - BRG1/SMARCA4 inactivation promotes non-small cell lung cancer aggressiveness by altering chromatin organization. AB - SWI/SNF chromatin remodeling complexes regulate critical cellular processes, including cell-cycle control, programmed cell death, differentiation, genomic instability, and DNA repair. Inactivation of this class of chromatin remodeling complex has been associated with a variety of malignancies, including lung, ovarian, renal, liver, and pediatric cancers. In particular, approximately 10% of primary human lung non-small cell lung cancers (NSCLC) display attenuations in the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1 attenuation in NSCLC development, we examined the effect of BRG1 silencing in primary and established human NSCLC cells. BRG1 loss altered cellular morphology and increased tumorigenic potential. Gene expression analyses showed reduced expression of genes known to be associated with progression of human NSCLC. We demonstrated that BRG1 losses in NSCLC cells were associated with variations in chromatin structure, including differences in nucleosome positioning and occupancy surrounding transcriptional start sites of disease-relevant genes. Our results offer direct evidence that BRG1 attenuation contributes to NSCLC aggressiveness by altering nucleosome positioning at a wide range of genes, including key cancer-associated genes. PMID- 25115303 TI - Drug resistance is conferred on the model yeast Saccharomyces cerevisiae by expression of full-length melanoma-associated human ATP-binding cassette transporter ABCB5. AB - ABCB5, an ATP-binding cassette (ABC) transporter, is highly expressed in melanoma cells, and may contribute to the extreme resistance of melanomas to chemotherapy by efflux of anti-cancer drugs. Our goal was to determine whether we could functionally express human ABCB5 in the model yeast Saccharomyces cerevisiae, in order to demonstrate an efflux function for ABCB5 in the absence of background pump activity from other human transporters. Heterologous expression would also facilitate drug discovery for this important target. DNAs encoding ABCB5 sequences were cloned into the chromosomal PDR5 locus of a S. cerevisiae strain in which seven endogenous ABC transporters have been deleted. Protein expression in the yeast cells was monitored by immunodetection using both a specific anti ABCB5 antibody and a cross-reactive anti-ABCB1 antibody. ABCB5 function in recombinant yeast cells was measured by determining whether the cells possessed increased resistance to known pump substrates, compared to the host yeast strain, in assays of yeast growth. Three ABCB5 constructs were made in yeast. One was derived from the ABCB5-beta mRNA, which is highly expressed in human tissues but is a truncation of a canonical full-size ABC transporter. Two constructs contained full-length ABCB5 sequences: either a native sequence from cDNA or a synthetic sequence codon-harmonized for S. cerevisiae. Expression of all three constructs in yeast was confirmed by immunodetection. Expression of the codon harmonized full-length ABCB5 DNA conferred increased resistance, relative to the host yeast strain, to the putative substrates rhodamine 123, daunorubicin, tetramethylrhodamine, FK506, or clorgyline. We conclude that full-length ABCB5 can be functionally expressed in S. cerevisiae and confers drug resistance. PMID- 25115304 TI - Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. AB - BACKGROUND: Monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) prolong survival in metastatic colorectal cancer (mCRC) Kirsten rat sarcoma viral oncogene (KRAS) exon 2 wild-type tumors. Recent evidence has suggested that other RAS mutations (in exons 3 and 4 of KRAS and exons 2, 3 and 4 of a related gene, NRAS) may also be predictive of resistance. METHODS: Systematic review and meta-analysis of randomized, controlled trials (RCTs) evaluating anti-EGFR mAbs that have assessed tumors for new RAS mutations. Tumors with the new RAS mutations were compared with both tumors without any RAS mutations and tumors with KRAS exon 2 mutations with respect to anti-EGFR treatment progression-free survival (PFS) and overall survival (OS) benefit. RESULTS: Nine RCTs comprising a total of 5948 participants evaluated for both KRAS exon 2 and new RAS mutations met the inclusion criteria. Approximately 20% of KRAS exon 2 wild-type tumors harbored one of the new RAS mutations. Tumors without any RAS mutations (either KRAS exon 2 or new RAS mutations) were found to have significantly superior anti-EGFR mAb PFS (P < 0.001) and OS (P = 0.008) treatment effect compared with tumors with any of the new RAS mutations. No difference in PFS or OS benefit was evident between tumors with KRAS exon 2 mutations and tumors with the new RAS mutations. Results were consistent between different anti-EGFR agents, lines of therapy and chemotherapy partners. Anti-EGFR mAb therapy significantly improved both PFS {hazard ratio 0.62 [95% confidence interval (CI) 0.50-0.76]} and OS [hazard ratio 0.87 (95% CI 0.77-0.99)] for tumors without any RAS mutations. No PFS or OS benefit was evident with use of anti-EGFR mAbs for tumors harboring any RAS mutation (P > 0.05). CONCLUSION: Tumors harboring one of the new RAS mutations are unlikely to significantly benefit from anti-EGFR mAb therapy in mCRC. PMID- 25115305 TI - Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 25115306 TI - Effectiveness of 3 T PROPELLER DUO diffusion-weighted MRI in differentiating sinonasal lymphomas and carcinomas. AB - AIM: To evaluate the value of 3 T Periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) DUO diffusion-weighted MRI (DW-MRI) in differentiating sinonasal lymphomas from carcinomas. MATERIALS AND METHODS: PROPELLER DUO DW-MRI was performed in 23 patients with sinonasal lymphomas and 28 patients with carcinomas histologically confirmed at 3 T MRI. Apparent diffusion coefficients (ADCs) were obtained with two different b-values (b = 0 and 700 s/mm(2), b = 0 and 1000 s/mm(2)) and two different regions of interest (ROIs) sampling strategies [whole section (WS), partial section (PS)], respectively. Difference in ADCs between sinonasal lymphomas and carcinomas was evaluated using the independent samples t-test or Mann-Whitney U-test. The utility of ADC thresholds for discriminating between them was evaluated by receiver operating characteristic analysis. RESULTS: ADCs of sinonasal lymphomas (WS ADCb0,700, 0.838 * 10(-3) mm(2)/s) were significantly (p < 0.001) lower than those of carcinomas (WS ADCb0,700, 1.396 * 10(-3) mm(2)/s). Using a WS ADC b0,700 value of 1.040 * 10(-3) mm(2)/s as the threshold value effectively differentiated sinonasal lymphomas from carcinomas with 100% sensitivity, 82.1% specificity, and 82.1% positive and 100% negative predictive values and 90.2% accuracy (b = 0, 700 s/mm(2)). There was no significant difference in diagnostic ability between different b-values settings (p > 0.05) and different sampling strategies of ROIs (p > 0.05), respectively. Additionally, there was significant differences in the ADCs between diffuse large B-cell lymphomas and natural killer (NK)/T-cell lymphomas (p < 0.05). CONCLUSION: PROPELLER DUO DW-MRI can effectively differentiate sinonasal lymphomas from carcinomas. PMID- 25115307 TI - Re: Are radiologists the contemporary anatomists? PMID- 25115310 TI - Revealing the substrate origin of the linear dispersion of silicene/Ag(111). AB - The band structure of the recently synthesized (3 * 3) silicene monolayer on (4 * 4) Ag(111) is investigated using density functional theory. A k-projection technique that includes the k?-dependence of the surface bands is used to separate the contributions arising from the silicene and the substrate, allowing a consistent comparison between the calculations and the angle-resolved photoemission experiments. Our calculations not only reproduce the observed gap and linear dispersion across the K point of (1 * 1) silicene but also demonstrate that these originate from the k?-dependence of Ag(111) substrate states (modified by interactions with the silicene) and not from a Dirac state. PMID- 25115309 TI - Pharmacological actions of thymol and an analogue at GABAB autoreceptors. AB - GABAB autoreceptors inhibit release of GABA from GABAergic nerve terminals. Agonists of these receptors (e.g. baclofen) inhibit, whereas antagonists (e.g. (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; Sch 50911) enhance release of the transmitter. The actions of thymol (2-isopropyl-5-methylphenol) and the structurally related compound 2-tert-butyl-4-methylphenol, (4MP) on the release of [(3) H]-GABA were examined in rat neocortical slices where the GABAergic nerves had been preloaded with [(3) H]-GABA and subsequently stimulated electrically on two occasions (S1 and S2 ). Test agents, baclofen and Sch 50911 were added to the superfusion medium prior to the second period of stimulation (S2 ). Stimulation-induced overflow (SIO) of [(3) H]-GABA as a consequence of these stimulations (SIO1 and SIO2 ) were calculated and the effects of agents determined by comparing the SIO2 /SIO1 ratio in the presence of each agent with that in control tissue. Thymol potentiated the release of [(3) H]-GABA (EC50 170 MUmol/L), an action reversed by baclofen (2 MUmol/L). Baclofen alone had little effect on GABA release. Release of [(3) H]-GABA was inhibited by 4MP (IC50 3 MUmol/L) and this effect was blocked by Sch 50911 (10 MUmol/L). Alone, Sch 50911 markedly potentiated the release of GABA. These results imply that 4MP is an agonist of GABAB autoreceptors; however, further studies are needed to confirm that thymol is indeed a GABAB autoreceptor antagonist. Of interest are structural differences in these agents. Thymol has a propyl group in the ortho position relative to the phenolic hydroxyl, whereas in 4MP this is a butyl group and the methyl group moves from position 5 to 4. Whether one or both of these changes was responsible for the above actions is unknown. PMID- 25115308 TI - Neck-specific training with a cognitive behavioural approach compared with prescribed physical activity in patients with cervical radiculopathy: a protocol of a prospective randomised clinical trial. AB - BACKGROUND: Patients with cervical radiculopathy often have neck- and arm pain, neurological changes, activity limitations and difficulties in returning to work. Most patients are not candidates for surgery but are often treated with different conservative approaches and may be sick-listed for long periods. The purpose of the current study is to compare the effectiveness of neck-specific training versus prescribed physical activity. METHODS/DESIGN: The current protocol is a two armed intervention randomised clinical trial comparing the outcomes of patients receiving neck specific training or prescribed physical activity. A total of 144 patients with cervical radiculopathy will be randomly allocated to either of the two interventions. The interventions will be delivered by experienced physiotherapists and last 14 weeks. The primary outcome variable is neck- and arm pain intensity measured with a Visual Analogue Scale accompanied with secondary outcome measures of impairments and subjective health measurements collected before intervention and at 3, 6, 12 and 24 months after base-line assessment. DISCUSSION: We anticipate that the results of this study will provide evidence to support recommendations as to the effectiveness of conservative interventions for patients with cervical radiculopathy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01831271. PMID- 25115311 TI - Educational intervention to improve the health outcomes of children with sickle cell disease. AB - INTRODUCTION: Although sickle cell disease (SCD) is the most common single gene disorder worldwide, caregivers of children do not have adequate knowledge about the illness and its management. The purpose of this study was to assess the efficacy of education along with tailored written materials in changing the behaviors of caregivers to help them provide better care for children with SCD. METHODS: A preintervention and postintervention quasi-experimental design was used. A convenience sample of 43 caregivers of 57 children were asked to complete a questionnaire related to their knowledge of SCD before and after educational sessions. The educational sessions (the intervention) were provided to caregivers at the Children's Cancer Center in Lebanon by one registered nurse, one certified pediatric nurse practitioner, and one pediatric hematologist. Emergency department (ED) visits and hospitalizations were compared 2 months before and 2 months after the intervention. RESULTS: A statistically significant increase was found in the knowledge of caregivers about the cause, symptoms, and management of the disease. A statistically significant decrease occurred in the number of hospitalizations before and after the intervention but not in the number of visits to the ED. Multiple regression analysis found that none of the background variables were related to knowledge, ED visits, or hospitalizations. CLINICAL IMPLICATIONS: Education and written materials written in a simple language that is understood by 5th-graders were beneficial in improving the knowledge of caregivers and in decreasing the number of hospitalizations of children with SCD. PMID- 25115312 TI - Adolescent with Fever, hypotension, and respiratory distress. PMID- 25115313 TI - Role of near-infrared fluorescence imaging in head and neck cancer surgery: from animal models to humans. AB - Complete resection of head and neck cancers with negative surgical margins improves the prognosis of the disease and decreases the recurrence rate. Near infrared fluorescence-guided surgery of head and neck cancer is a rapidly evolving field that represents an invaluable tool for tumor detection and resection. Here, we present a literature review of the principles of near infrared fluorescence imaging and its use in head and neck cancer surgery. We discuss important studies in both animal models and humans that have been carried out up to this point. We also outline the important fluorescent molecules and devices used in head and neck fluorescence imaging-guided surgery. Although near infrared fluorescence-guided surgery for head and neck cancers showed efficacy in animal models, its use in humans is limited by the small number of fluorescent probes that are approved for clinical use. However, it is considered as a novel surgical aid that helps delineate tumor margins preoperatively and could spare patients from the added morbidity that is associated with additional surgery or chemoradiation. In addition, it is a useful tool to detect sentinel lymph nodes as well as metastatic lymph nodes. PMID- 25115314 TI - Association between sudden sensorineural hearing loss and anxiety disorder: a population-based study. AB - Anxiety disorder (AD) is commonly associated with a number of physical illnesses. No previous study has investigated the association between AD and sudden sensorineural hearing loss (SSNHL). In this study, we investigated the association between prior AD and SSNHL using a population-based dataset in Taiwan. Sampled subjects of this case-control study were retrieved from the Taiwan "Longitudinal Health Insurance Database". We identified 3,522 patients who had a diagnosis of SSNHL as cases and 10,566 age- and gender-matched subjects without SSNHL as controls. A conditional logistic regression was used to calculate the odds ratio (OR) for having previously been diagnosed with AD between cases and controls. We found that of 14,088 patients, 13.4% had a prior AD diagnosis, 17.8 and 11.9% for the SSNHL group and controls, respectively. After adjusting for patient socioeconomic characteristics and comorbid medical disorders, SSNHL patients were more likely to have prior AD than the controls (OR 1.49, 95% confidence interval (CI) 1.34-1.66, p < 0.001). Furthermore, we found that the significant relationship between SSNHL and prior AD decreased with age. The relationship was the most pronounced among those aged <=44 years, with an adjusted OR of 1.86 (95% CI 1.48-2.33, p < 0.001) for cases compared to controls. We concluded that patients with SSNHL had a higher proportion of prior AD than non-SSNHL-diagnosed controls. Further study is needed to confirm our findings and explore the underlying pathomechanisms. PMID- 25115315 TI - Orbital compartment: effects of emergent canthotomy and cantholysis. AB - The objective of this study was to determine the effect of orbital decompression procedures on the intraocular pressure (IOP). The orbital compartment syndrome represents an emergency situation. Due to the elevated IOP vision loss may ensue. Several maneuvers including lateral canthotomy are discussed to reduce the IOP. Eight orbits were studied in a fresh frozen cadaveric model (4 specimens). Intraorbital volume was determined by CT volumetry. An orbital compartment syndrome was simulated by injecting viscous material into the orbit. Injected volumes were documented and lateral canthotomy, cantholysis, inferior and superior septolysis were performed. IOP and exophthalmometric measurements were obtained after each intervention. Controlled elevation of IOP was achieved in all specimens. IOP was partially reduced after performing a lateral canthotomy in eight orbits. IOP was significantly and sufficiently decreased under 20 mmHg by inferior cantholysis in seven orbits. An additional superior cantholysis was necessary in two orbits to achieve a complete decompression. Inferior or superior septolysis were not needed to further reduce the IOP. Lateral canthotomy must be followed by an inferior cantholysis to successfully decompress an orbital compartment syndrome in the majority of cases. Occasionally, superior cantholysis may generate additional benefit. Additional inferior and superior septolysis were not shown to provide a beneficial effect when performed after canthotomy and cantholysis. PMID- 25115317 TI - Early dermoscopic detection of lentigo maligna within a lesion of pigmented contact dermatitis. PMID- 25115316 TI - Steroids and antihistamines synergize to inhibit rat's airway smooth muscle contractility. AB - Both glucocorticoids and H1-antihistamines were widely used on patients with allergic rhinitis (AR) and obstructive airway diseases. However, their direct effects on airway smooth muscle were not fully explored. In this study, we tested the effectiveness of prednisolone (Kidsolone) and levocetirizine (Xyzal) on isolated rat trachea submersed in Kreb's solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following assessments of the drug were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10(-6) M methacholine; (3) effect of the drug on electrical field stimulation (EFS) induced tracheal smooth muscle contractions. The result revealed sole use of Kidsolone or Xyzal elicited no significant effect or only a little relaxation response on tracheal tension after methacholine treatment. The tension was 90.5 +/- 7.5 and 99.5 +/- 0.8 % at 10(-4) M for Xyzal and 10(-5) M for Kidsolone, respectively. However, a dramatically spasmolytic effect was observed after co-administration of Kidsolone and Xyzal and the tension dropped to 67.5 +/- 13.6 %, with statistical significance (p < 0.05). As for EFS-induced contractions, Kidsolone had no direct effect but Xyzal could inhibit it, with increasing basal tension. In conclusion, using glucocorticoids alone had no spasmolytic effect but they can be synergized with antihistamines to dramatically relax the trachea smooth muscle within minutes. Therefore, for AR patients with acute asthma attack, combined use of those two drugs is recommended. PMID- 25115318 TI - Substance abuse-specific knowledge transfer or loss? Treatment program turnover versus professional turnover among substance abuse clinicians. AB - This longitudinal study investigated the extent to which substance abuse (SA) clinician turnover is associated with SA-specific knowledge loss due to change in professions (professional turnover) versus SA-specific knowledge transfer due to movement from one SA clinical setting to another (treatment program turnover). For this study, clinicians had to have voluntarily left their current treatment program. Eligible clinicians completed a quantitative survey while employed and a qualitative post-employment exit interview 1 year later. Compared to those that exited the SA profession (n = 99), clinicians who changed treatment programs (n = 120) had greater SA-specific formal knowledge and were more likely to be personally in recovery. No differences were found between the two groups in terms of SA-specific practical knowledge. PMID- 25115320 TI - Response to chemotherapy, reexposure to crizotinib and treatment with a novel ALK inhibitor in a patient with acquired crizotinib resistance. AB - The treatment of advanced non-small cell lung cancer (NSCLC) has dramatically changed over the last decade. It has developed from an unspecific approach based on platinum doublet chemotherapy to a personalized, molecularly targeted therapy. Crizotinib is a new tyrosine kinase inhibitor approved for the treatment of NSCLC with gene rearrangement of EML4 and ALK. Despite good initial responses, patients treated with crizotinib relapse after an average of 10 months. In this case report, we present a patient with acquired crizotinib resistance whose adenocarcinoma responded to a second course of crizotinib following a drug holiday and chemotherapy with pemetrexed. This is the second case report to suggest that retreatment with crizotinib is an option for patients with initial benefit from ALK inhibition. PMID- 25115319 TI - Pregnancy outcomes and birth defects from an antiretroviral drug safety study of women in South Africa and Zambia. AB - OBJECTIVE: To evaluate the safety of combination antiretroviral therapy (ART) in conception and pregnancy in different health systems. DESIGN: A pilot ART registry to measure the prevalence of birth defects and adverse pregnancy outcomes in South Africa and Zambia. METHODS: HIV-infected pregnant women on ART prior to conception were enrolled until delivery, and their infants were followed until 1 year old. RESULTS: Between October 2010 and April 2011, 600 women were enrolled. The median CD4 cell count at study enrollment was lower in South Africa than Zambia (320 vs. 430 cells/MUl; P < 0.01). The most common antiretroviral drugs at the time of conception included stavudine, lamivudine, and nevirapine. There were 16 abortions (2.7%), one ectopic pregnancy (0.2%), 12 (2.0%) stillbirths, and 571 (95.2%) live infants. Deliveries were more often preterm (29.7 vs. 18.4%; P = 0.01) and the infants had lower birth weights (2900 vs. 2995 g; P = 0.11) in Zambia compared to South Africa. Thirty-six infants had birth defects: 13 major and 23 minor. There were more major anomalies detected in South Africa and more minor ones in Zambia. No neonatal deaths were attributed to congenital birth defects. CONCLUSIONS: An Africa-specific, multi-site antiretroviral drug safety registry for pregnant women is feasible. Different prevalence for preterm delivery, delivery mode, and birth defect types between women on preconception ART in South Africa and Zambia highlight the potential impact of health systems on pregnancy outcomes. As countries establish ART drug safety registries, documenting health facility limitations may be as essential as the specific ART details. PMID- 25115321 TI - Long-term psychosocial impact of otoplasty performed on children with prominent ears. AB - OBJECTIVES: To investigate the psychosocial impact of prominent ears on children, and evaluate the outcomes of otoplasty two years after surgery, using the Child Behavior Checklist to comparatively evaluate patients' psychosocial profiles. METHOD AND RESULTS: A total of 198 otoplasty procedures were performed in 107 patients (85 per cent bilateral procedures). Otoplasty was performed solely in 86 patients and concurrently with other procedures in 21 patients. All children who underwent surgery obtained good post-operative results, with satisfactory correction of the deformity reported by the patients and their parents or guardians. There were statistically significant decreases in Child Behavior Checklist scores in the domains of: anxiety and depression (p = 0.028), social problems (p = 0.018), difficulties in thinking (p = 0.012), total behavioural problems (p = 0.012), internalising problems (p = 0.020) and externalising problems (p = 0.044), and near-significant decreases in scores for attention problems (p = 0.055) and aggressive behaviour (p = 0.078). There was a statistically significant increase in the score for total social competence (p = 0.031). CONCLUSION: Psychological problems associated with anatomical deformities such as prominent ears can be reduced by means of appropriate corrective surgery. Psychological support is necessary for the patient. PMID- 25115322 TI - Magnetic resonance imaging in lumbar gunshot wounds: an absolute contraindication? AB - OBJECT: Performance of MR imaging in patients with gunshot wounds at or near the lumbar spinal canal is controversial. The authors reviewed the literature on the use of MR imaging in gunshot wounds to the spine. They discuss the results from in vitro and clinical studies, analyze the physical properties of common projectiles, and evaluate the safety and indications for MR imaging when metallic fragments are located near the spinal canal. METHODS: A review of the English language literature was performed. Data from 25 articles were analyzed, including 5 in vitro studies of the interaction between 95 projectiles and the MR system's magnetic fields, and the clinical outcomes in 22 patients with metallic fragments at or near the spinal canal who underwent MR imaging. RESULTS: Properties of 95 civilian and military projectiles were analyzed at a magnet strength of 1, 1.5, 3, and 7 T. The most common projectiles were bullets with a core of lead, either with a copper jacket or unjacketed (73 [76.8%] of 95). Steel-containing (core or jacket) projectiles comprised 14.7%. No field interaction was evident in 78 (96.3%) of the 81 nonsteel projectiles. All steel projectiles showed at least positive deflection forces, longitudinal migration, or rotation. Heating of the projectiles was clinically insignificant. Image artifact was significant in all 9 steel bullets tested, but was not significant in 39 (88.6%) of the 44 nonsteel bullets tested. Overall, 22 patients with complete (82%) and incomplete (14%) spinal cord injury secondary to a projectile lodged inside the spinal canal underwent MR imaging. Discomfort and further physical or neurological deficits were not reported by any patient. Two patients with spinal cord injuries underwent MR imaging studies before surgical decompression and had subsequent, significant neurological improvement. CONCLUSIONS: Metallic implants near or at the spinal canal are a relative contraindication for MR imaging. However, safe MR imaging might be feasible when a projectile's properties and a patient's individualized clinical presentation are considered. PMID- 25115323 TI - The association between bullying-related behaviours and subjective health complaints in late adolescence: cross-sectional study in Greece. AB - BACKGROUND: Bullying is quite prevalent in the school setting and has been associated with several subjective health complaints such as headache, backache, abdominal pain, dizziness, fatigue and sleep problems. The aim of the present study was to investigate the association between bullying and subjective health complaints in a sample of Greek adolescents taking into account the presence of psychiatric morbidity. METHODS: A stratified random sample of 2427 adolescents aged 16-18 years old and attending senior high schools were randomly selected for a computerized interview. Subjective health complaints were assessed using a symptom checklist used in the context of a previous World Health Organization study and relevant sections of the revised Clinical Interview Schedule (CIS-R). The latter was also used for the assessment of psychiatric morbidity. Bullying was assessed with the revised Olweus bully/victim questionnaire. A series of logistic regression models were used to investigate the association between bullying and subjective health complaints. RESULTS: Victims of bullying were more likely to report backache (Odds Ratio [OR] = 1.92, 95% CI: 1.01-3.67), dizziness (OR = 2.83, 95% CI: 1.11-7.22) and fatigue (OR = 0.41, 95% CI: 0.19-0.86), independently of the presence of psychiatric morbidity. In addition bullying perpetrators were more likely to report backache (OR = 3.49, 95% CI: 1.49-8.18). It is worth noting that sleep problems and abdominal pain were also associated with being bullied and fatigue with bullying perpetration but these associations were all attenuated after adjustment for psychiatric morbidity. CONCLUSIONS: Strong associations between bullying in schools and subjective health complaints among a sample of Greek students aged 16-18 years have been observed. The exact nature of these associations should be investigated in future longitudinal studies. PMID- 25115325 TI - Is sacral neuromodulation here to stay? Clinical outcomes of a new treatment for fecal incontinence. AB - INTRODUCTION: Sacral neuromodulation (SNM) was approved by the FDA for the treatment of fecal incontinence (FI) in 2011, and previous industry-sponsored trials have shown excellent clinical outcomes. The purpose of this study is to examine clinical outcomes of patients treated during our initial experience with SNM. METHODS: A prospective database of patients treated with SNM for FI by one of three colorectal surgeons at two separate institutions was maintained starting in 2011. Patients showing >=50% improvement of weekly incontinent episodes during test stimulation were offered permanent implantation of the SNM device. Disease severity was tracked using the Wexner score. RESULTS: A total of 145 patients received a full system implantation (of 152 who received test stimulation). The median preoperative Wexner score of 14 decreased to 3, 3 months after implantation and persisted to 12 months. At 12 months, 95.2% of patients achieved >50% improvement in Wexner Score and 67.6% achieved >75% improvement. The most common adverse event was infection (3.4%). Three patients (2.1%) required lead revision. CONCLUSIONS: SNM is a safe and effective therapy for the treatment of FI. Postoperative patient surveillance is important, as many patients require programming changes, and some will require a lead revision over time. PMID- 25115324 TI - Routine drainage of the operative bed following elective distal pancreatectomy does not reduce the occurrence of complications. AB - BACKGROUND: Routine drainage of the operative bed following elective pancreatectomy remains controversial. Data specific to distal pancreatectomy (DP) have not been examined in a multi-institutional collaborative. METHODS: Data from the American College of Surgeons-National Surgical Quality Improvement Program Pancreatectomy Demonstration Project were utilized. The impact of drain placement on development of pancreatectomy-related and overall morbidity were analyzed. Propensity scores for drain placement were calculated, and nearest neighbor matching was used to create a matched cohort. Groups were compared using bivariate and logistic regression analyses. RESULTS: Over 14 months, 761 patients undergoing DP were accrued; 606 were drained. Propensity score matching was possible in 116 patients. Drain and no drain groups were not different with respect to multiple preoperative and operative variables. All pancreatic fistulas (p < 0.01) and overall morbidity (p < 0.05) were more common in patients who received a drain. The placement of a drain did not reduce the incidence of clinically relevant pancreatic fistula nor the need for postoperative procedures. CONCLUSIONS: Placement of drains following elective distal pancreatectomy was associated with a higher overall morbidity and pancreatic fistulas. Drains did not reduce intra-abdominal septic morbidity, clinically relevant pancreatic fistulas, nor the need for postoperative therapeutic intervention. PMID- 25115327 TI - Pushing with the pigtail: a novel approach to placing the MitraClip in a patient with a severely restricted posterior mitral leaflet. AB - The MitraClip is an US Food and Drug Administration-approved device for inoperable patients with severe degenerative mitral regurgitation (MR) and is under investigation for use in patients with severe functional MR. Simultaneously grasping both leaflets of the mitral valve can be technically challenging, however, in patients with a restricted posterior leaflet. We present one such case in which a pigtail catheter, placed retrograde into the left ventricle, was able to push the ventricular surface of the posterior leaflet into closer approximation with the anterior leaflet, and facilitate successful clip placement. We provide this report in hopes that it will provide a useful strategy for interventionalists faced with this challenging situation. PMID- 25115326 TI - Superglue in the Urethra: Surgical Treatment. AB - We describe a case of superglue application into the male urethra with successful surgical treatment of the glue particles by external urethrotomy. PMID- 25115328 TI - 'A Speculative Idea': The Parallel Trajectories of Financial Speculation, Obstetrical Science, and Fiscal Management of Female Bodies in Henry James's Washington Square. AB - This essay teases out the intimate connections between the scientific and fiscal realms in the context of American germ theory and obstetrics. By uncovering the economic and medical contexts of Henry James's Washington Square-set during the infancy of germ theory and the heyday of American obstetrics-this essay exposes a previously unexplored subtextual history of contagion in the text. Although this scientific history seems relegated to the novel's margins, understanding the changing scientific cosmologies and professional organizations in the context of the novel's setting and composition reveals that these tiny infectious particles and their vectors fundamentally shape the plot of the novel. PMID- 25115329 TI - Phenyl amide linker improves the pharmacokinetics and pharmacodynamics of N terminally mono-PEGylated human growth hormone. AB - Human growth hormone (hGH) suffers from a short plasma half-life of ~15 min, necessitating frequent injections to maintain its physiological effect. PEGylation, conjugation of polyethylene glycol (PEG), is an effective strategy to prolong the plasma half-life of hGH. However, PEGylation can significantly decrease the bioactivity of hGH. Thus, a new PEGylation approach is desired to improve the pharmacokinetics (PK) and pharmacodynamics (PD) of the PEGylated hGH. In the present study, two N-terminally mono-PEGylated hGHs were prepared using aldehyde chemistry. Phenyl amide and ethyl moieties were used as the linkers between PEG and hGH, respectively. The hydrodynamic volume, proteolytic sensitivity, and immunogenicity of the PEGylated hGH with phenyl amide linker (hGH-phenyl-PEG) were lower than those of the one with propyl linker (hGH-prop PEG). In addition, hGH-phenyl-PEG showed a higher in vitro bioactivity and better PK and PD than hGH-prop-PEG. The better PK of hGH-phenyl-PEG was mainly due to its lower proteolytic sensitivity and low immunogenicity. The better PD of hGH phenyl-PEG was mainly due to its higher in vitro bioactivity. Thus, the phenyl amide linker can improve the overall pharmacological profiles of the PEGylated hGH. Our study is expected to advance the development of long-acting protein biotherapeutics with high therapeutic efficacy. PMID- 25115331 TI - KiMoSys: a web-based repository of experimental data for KInetic MOdels of biological SYStems. AB - BACKGROUND: The kinetic modeling of biological systems is mainly composed of three steps that proceed iteratively: model building, simulation and analysis. In the first step, it is usually required to set initial metabolite concentrations, and to assign kinetic rate laws, along with estimating parameter values using kinetic data through optimization when these are not known. Although the rapid development of high-throughput methods has generated much omics data, experimentalists present only a summary of obtained results for publication, the experimental data files are not usually submitted to any public repository, or simply not available at all. In order to automatize as much as possible the steps of building kinetic models, there is a growing requirement in the systems biology community for easily exchanging data in combination with models, which represents the main motivation of KiMoSys development. DESCRIPTION: KiMoSys is a user friendly platform that includes a public data repository of published experimental data, containing concentration data of metabolites and enzymes and flux data. It was designed to ensure data management, storage and sharing for a wider systems biology community. This community repository offers a web-based interface and upload facility to turn available data into publicly accessible, centralized and structured-format data files. Moreover, it compiles and integrates available kinetic models associated with the data.KiMoSys also integrates some tools to facilitate the kinetic model construction process of large-scale metabolic networks, especially when the systems biologists perform computational research. CONCLUSIONS: KiMoSys is a web-based system that integrates a public data and associated model(s) repository with computational tools, providing the systems biology community with a novel application facilitating data storage and sharing, thus supporting construction of ODE-based kinetic models and collaborative research projects.The web application implemented using Ruby on Rails framework is freely available for web access at http://kimosys.org, along with its full documentation. PMID- 25115333 TI - Endothelial cationic amino acid transporter-1 overexpression blunts the effects of oxidative stress on pressor responses to behavioural stress in mice. AB - Observational studies indicate that psychological stress may contribute to the pathogenesis of hypertension and this may be further accentuated by factors such as endothelial dysfunction. On this basis, we aimed to determine whether oxidative stress enhances pressor responses to stressful stimuli and whether augmenting endothelial function by increasing the transport of L-arginine can counter the effects of oxidative stress. Telemetry probes were used to measure mean arterial pressure (MAP) in wild-type (WT; n = 6) and endothelial cationic amino acid transporter-1 (CAT-1)-overexpressing (CAT+) mice (n = 6) before and during an aversive (restraint) and non-aversive (almond feeding) stressor. The superoxide dismutase inhibitor diethyldithiocarbamic acid (DETCA; 30 mg/kg per day; 14 days) was then administered via a minipump to induce oxidative stress. Stress responses to feeding and restraint were repeated during Days 11-12 of DETCA infusion. In WT mice, pressor responses to restraint and feeding were augmented during infusion of DETCA (35 +/- 1 and 28 +/- 1 mmHg, respectively) compared with respective pretreatment responses (28 +/- 2 and 24 +/- 1 mmHg, respectively; P <= 0.01). In CAT+ mice, pressor responses to feeding were blunted during DETCA (20 +/- 1 mmHg) compared with the control response (23 +/- 1 mmHg; P = 0.03). In these mice, pressor responses to restraint were similar before (28 +/ 1 mmHg) and during (26 +/- 1 mmHg) DETCA infusion (P = 0.26). We conclude that endothelial CAT-1 overexpression can counter the ability of oxidative stress to augment pressor responses to behavioural stress. PMID- 25115334 TI - Effects of framework design and layering material on fracture strength of implant supported zirconia-based molar crowns. AB - OBJECTIVES: To evaluate the effects of framework design and layering material on the fracture strength of implant-supported zirconia-based molar crowns. MATERIAL AND METHODS: Sixty-six titanium abutments (GingiHue Post) were tightened onto dental implants (Implant Lab Analog). These abutment-implant complexes were randomly divided into three groups (n = 22) according to the design of the zirconia framework (Katana), namely, uniform-thickness (UNI), anatomic (ANA), and supported anatomic (SUP) designs. The specimens in each design group were further divided into two subgroups (n = 11): zirconia-based all-ceramic restorations (ZAC group) and zirconia-based restorations with an indirect composite material (Estenia C&B) layered onto the zirconia framework (ZIC group). All crowns were cemented on implant abutments, after which the specimens were tested for fracture resistance. The data were analyzed with the Kruskal-Wallis test and the Mann Whitney U-test with the Bonferroni correction (alpha = 0.05). RESULTS: The following mean fracture strength values (kN) were obtained in UNI design, ANA design, and SUP design, respectively: Group ZAC, 3.78, 6.01, 6.50 and Group ZIC, 3.15, 5.65, 5.83. In both the ZAC and ZIC groups, fracture strength was significantly lower for the UNI design than the other two framework designs (P = 0.001). Fracture strength did not significantly differ (P > 0.420) between identical framework designs in the ZAC and ZIC groups. CONCLUSIONS: A framework design with standardized layer thickness and adequate support of veneer by zirconia frameworks, as in the ANA and SUP designs, increases fracture resistance in implant-supported zirconia-based restorations under conditions of chewing attrition. Indirect composite material and porcelain perform similarly as layering materials on zirconia frameworks. PMID- 25115335 TI - Evaluation of IAUGC indices and two DCE-MRI pharmacokinetic parameters assessed by two different theoretical algorithms in patients with brain tumors. AB - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantifies blood brain barrier (BBB) microvascular permeability in brain tumors where it is structurally and functionally abnormal. Twenty-five patients with glioblastomas (105 regions of interest) were compared using DCE-MRI metrics obtained with Tofts Kety (TK) and extended TK (ETK) models using different arterial input function assessments and different initial area under the gadolinium curve (IAUGC) indices. Strong correlations between ve and IAUGC90 were found (EKT model: R=0.75 and R=0.69), while correlations of K(trans) with both IAUGC80/90 indices were weak. Differences in the permeability parameters, calculated by these two models, were found. While the IAUGC method can be implemented more easily than pharmacokinetic models, at this time, the IAUGC approach alone does not substitute pharmacokinetic models in BBB permeability characterization. PMID- 25115336 TI - A new filaggrin gene mutation in a Korean patient with ichthyosis vulgaris. PMID- 25115332 TI - Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis. AB - BACKGROUND: Some of cannabinoids, which are chemical compounds contained in marijuana, are immunosuppressive. One of the receptors, CB receptor 1 (CB1), is expressed predominantly by the cells in the central nervous system, whereas CB receptor 2 (CB(2)) is expressed primarily by immune cells. Theoretically, selective CB(2) agonists should be devoid of psychoactive effects. In this study, we investigated therapeutic effects of a selective CB(2) agonist on arthritis. METHODS: The expression of CB(2) was analyzed with immunohistochemistry and Western blotting. Interleukin (IL)-6, matrix metalloproteinase-3 (MMP-3), and chemokine (C-C motif) ligand 2 (CCL2) were quantified with enzyme-linked immunosorbent assays (ELISA). Osteoclastogenesis was assessed with tartrate resistant acid phosphatase staining and the resorption of coated-calcium phosphate. Effect of JWH133, a selective CB(2) agonist, on murine collagen type II (CII)-induced arthritis (CIA) was evaluated with arthritis score, and histological and radiographic changes. IFN-gamma and IL-17 production by CII stimulated splenocytes and serum anti-CII Ab were analyzed by ELISA. RESULTS: Immunohistochemistry showed that CB(2) was expressed more in the synovial tissues from the rheumatoid joints than in those from the osteoarthritis joints. CB(2) expression on RA FLS was confirmed with Western blot analysis. JWH133 inhibited IL-6, MMP-3, and CCL2 production from tumor necrosis factor-alpha-stimulated fibroblast-like synoviocytes (FLS) derived from the rheumatoid joints, and osteoclastogenesis of peripheral blood monocytes. Administration of JWH133 to CIA mice reduced the arthritis score, inflammatory cell infiltration, bone destruction, and anti-CII IgG1 production. CONCLUSION: The present study suggests that a selective CB(2) agonist could be a new therapy for RA that inhibits production of inflammatory mediators from FLS, and osteoclastogenesis. PMID- 25115337 TI - Three-dimensional bicomponent supramolecular nanoporous self-assembly on a hybrid all-carbon atomically flat and transparent platform. AB - Molecular self-assembly is a versatile nanofabrication technique with atomic precision en route to molecule-based electronic components and devices. Here, we demonstrate a three-dimensional, bicomponent supramolecular network architecture on an all-carbon sp(2)-sp(3) transparent platform. The substrate consists of hydrogenated diamond decorated with a monolayer graphene sheet. The pertaining bilayer assembly of a melamine-naphthalenetetracarboxylic diimide supramolecular network exhibiting a nanoporous honeycomb structure is explored via scanning tunneling microscopy initially at the solution-highly oriented pyrolytic graphite interface. On both graphene-terminated copper and an atomically flat graphene/diamond hybrid substrate, an assembly protocol is demonstrated yielding similar supramolecular networks with long-range order. Our results suggest that hybrid platforms, (supramolecular) chemistry and thermodynamic growth protocols can be merged for in situ molecular device fabrication. PMID- 25115338 TI - The forgotten members of the glucagon family. AB - From proglucagon, at least six final biologically active peptides are produced by tissue-specific post-translational processing. While glucagon and GLP-1 are the subject of permanent studies, the four others are usually left in the shadow, in spite of their large biological interest. The present review is devoted to oxyntomodulin and miniglucagon, not forgetting glicentin, although much less is known about it. Oxyntomodulin (OXM) and glicentin are regulators of gastric acid and hydromineral intestinal secretions. OXM is also deeply involved in the control of food intake and energy expenditure, properties that make this peptide a credible treatment of obesity if the question of administration is solved, as for any peptide. Miniglucagon, the C-terminal undecapeptide of glucagon which results from a secondary processing of original nature, displays properties antagonistic to that of the mother-hormone glucagon: (a) it inhibits glucose-, glucagon- and GLP-1-stimulated insulin release at sub-picomolar concentrations, (b) it reduces the in vivo insulin response to glucose with no change in glycemia, (c) it displays insulin-like properties at the cellular level using only a part of the pathway used by insulin, making it a good basis for developing a pharmacological workaround of insulin resistance. PMID- 25115339 TI - Study to assess whether waist circumference and changes in serum glucose and lipid profile are independent variables for the CETP gene. AB - AIMS: To observe the relationship among genes, obesity and the changes in serum glucose and lipid profile to assess whether obesity-related disease results from genes and/or obesity. METHODS: Correlations among serum glucose, lipids, waist circumference (WC), and Taq1B, I405V, and D442G polymorphisms of the cholesteryl ester transfer protein (CETP) gene were assessed. Logistic regression analysis was used to screen independent variables among obesity-related anthropometric indexes and serum biochemical indicators for genes. RESULTS: The waist circumference density index (WCDI) may be attributed to changes in serum biochemical indicators and among WCDI, BMI and serum biochemical indicators, however, only WCDI was an independent variable for the G allele. Differences were observed in anthropometric indexes and serum biochemical indicators between subjects with the G allele and those without (p<0.05). CONCLUSION: Abdominal obesity and changes in serum glucose and lipid profile are affected by a group of genes, including CETP. Correlation of the CETP gene with waist circumference may be independent compared with serum glucose and lipid profile. PMID- 25115340 TI - Prevalence and correlates of alcohol abuse and dependence in Lebanon: results from the Lebanese Epidemiologic Survey on Alcohol (LESA). AB - The current article aimed to determine the 12-month prevalence and correlates of DSM-IV alcohol abuse and dependence in a nationally representative sample of Lebanese adults. One thousand participants collaborated in face-to-face interviews in 2011. Prevalence of 12-month alcohol dependence was 5%, with a higher risk for those who were men, unmarried, the youngest adults (aged between 18 and 34 years old), students, participants with a liberal occupation, participants with a low income, participants with a positive family history of alcohol misuse, and smokers. Prevalence of 12-month alcohol abuse was 6.2%, with a higher risk for those who were men, students, employees, and Druze and Christians compared to Muslims. Current alcohol abuse and dependence were found to be very highly prevalent in Lebanon. PMID- 25115341 TI - Cross-reacting material 197, a heparin-binding EGF-like growth factor inhibitor, reverses the chemoresistance in human cisplatin-resistant ovarian cancer. AB - Cross-reacting material 197 (CRM197), a specific HB-EGF inhibitor, has been proven to be a promising antitumor agent for ovarian cancer therapy. Our previous studies have shown that CRM197 has potent antitumor activity in human cisplatin resistant ovarian cancer. However, the relationship between CRM197 and the resistance to cisplatin remains unclear. Here, we report that CRM197 significantly reverses the resistance to cisplatin in cisplatin-resistant ovarian carcinoma cell line (A2780/CDDP). We established xenograft nude mice models with A2780 and A2780/CDDP cells. Notably, we observed that CRM197 suppresses the expression of HB-EGF and epidermal growth factor receptor in A2780/CDDP cells and xenografts harboring the overexpression of HB-EGF and epidermal growth factor receptor. Experiments conducted in vitro and in vivo suggest that CRM197 markedly downregulates the expression of excision repair cross-complementing group 1 (P = 0.002) and DNA repair capacity in A2780/CDDP tumor (P < 0.001) by inactivation of extracellular signal-regulated kinase signaling, providing novel possible mechanisms for the ability of CRM197 to restore drug sensitivity. These results suggest that CRM197 as an HB-EGF inhibitor might be a cisplatin-chemosensitizing agent for the treatment of ovarian carcinoma with resistance to cisplatin. PMID- 25115342 TI - Nab-paclitaxel for the management of triple-negative metastatic breast cancer: a case study. AB - The optimal sequence of systemic chemotherapy in metastatic breast cancer (MBC) is unknown. We report the case of a woman who was successfully treated with nanoparticle albumin-bound (nab)-paclitaxel for triple negative MBC in our institution. In November 2008, a 48-year-old woman underwent surgical treatment for a triple negative invasive ductal breast cancer and subsequently received adjuvant chemotherapy with fluorouracil/epirubicin/cyclophosphamide and radiotherapy. Sixteen months after surgery, she presented with a left chest wall metastatasis. The patient received combination therapy with conventional paclitaxel (90 mg/m2 weekly for 3 out of 4 weeks [QW 3/4]) and bevacizumab (10 mg/kg every 2 weeks [Q2W]) as first-line treatment for MBC (six cycles; March to September 2010) and achieved a partial response at the metastatic site. Bevacizumab monotherapy was continued until disease progression (April 2011) with the development of a single infraclavicular lymph node metastasis and an increase in the dimensions of the left chest wall lesion. From May to December 2011, the patient received nab-paclitaxel 260 mg/m2 every 3 weeks (Q3W) as second-line treatment (11 cycles). After three cycles, the left chest wall lesion and the infraclavicular lymph node metastasis were undetectable and the patient was considered to have achieved a complete response. Treatment was well tolerated with no significant toxicity or need for dose reduction. Given our case, here we review the clinical evidence and discuss the potential role of nab-paclitaxel for the treatment of triple negative MBC, a subgroup typically characterized as having aggressive disease and limited treatment options. PMID- 25115343 TI - Methicillin-resistant Staphylococcus aureus infection: an independent risk factor for mortality in patients with poststernotomy mediastinitis. AB - OBJECTIVE: The mortality rate of patients with poststernotomy mediastinitis remains very high. The aim of this study was to identify the risk factors associated with mortality in these patients. SUBJECTS AND METHODS: Surveillance of sternal surgical-site infections including mediastinitis was carried out for adult patients undergoing a sternotomy between 2004 and 2012. Criteria from the US Centers for Disease Control and Prevention were used to make the diagnosis. All data on patients with a diagnosis of mediastinitis who were included in the study and on mortality risk factors were obtained from the hospital database and then analyzed using SPPS 16.0 for Windows. RESULTS: Of the 19,767 patients undergoing open heart surgery, 117 (0.39%) had poststernotomy mediastinitis; 32% of these 117 died. The independent risk factors for mortality were methicillin resistant Staphylococcus aureus (MRSA) [odds ratio (OR) 12.11 and 95% confidence interval (CI) 3.15-46.47], intensive-care unit stays >48 h after the first operation (OR 11.21 and 95% CI 3.24-38.84) and surgery that included valve replacement (OR 6.2 and 95% CI 1.44-27.13). The mortality rate decreased significantly, dropping from 38% (34/89) between 2004 and 2008 to 14% (4/28) between 2009 and 2012 (p = 0.018). CONCLUSION: In this study, elimination of MRSA from the hospital setting decreased the rate of mortality in patients with poststernotomy mediastinitis. PMID- 25115344 TI - Effects of dietary threonine and tryptophan supplementation on growing pigs induced by porcine respiratory and reproductive syndrome vaccination. AB - A total of 32 growing pigs were used in a 2 * 2 factorial arrangement of treatments with two different diets (conventional [CON] diet vs. threonine [Thr]- and tryptophan [Trp]-rich [TTR] diet) and two immunological challenge regimens (porcine respiratory and reproductive syndrome [PRRS] vaccine vs. phosphate buffer solution [PBS]) to study the hypothesis that dietary supplementation with Trp and Thr would benefit for growing pigs vaccinated with PRRS vaccine. After feeding the experimental diets for 21 d, the pigs were intramuscularly vaccinated with PRRS or PBS. Performance data were recorded over a period of 10 weeks and are presented for the pre-challenge period (3 weeks) and the challenge period (7 weeks, where on day 1, pigs were immunologically challenged). During the pre challenge period, the growth performance was not different between dietary treatments. PRRS vaccination resulted in increased rectal temperature and decreased feed intake and growth rate (p < 0.05). In PRRS-vaccinated pigs, diet TTR enhanced the feed intake, especially during the first 2 weeks after the PRRS vaccination compared with diet CON (p < 0.05). PRRS vaccination also resulted in increased plasma concentration of urea nitrogen, essential and non-essential amino acids (p < 0.05) and porcine reproductive and respiratory syndrome virus specific antibodies (p < 0.05), but decreased concentration of immunoproteins including alpha-1-acylglycoprotein and immunoglobulin G (p < 0.05). The alleviation of the PRRS vaccination induced decrease in feed intake and growth rate by Thr and Trp supplementation, indicating that the PRRS-vaccinated pigs had a higher Thr and Trp requirement than non-vaccinated pigs. PMID- 25115345 TI - Management of obesity in children differs from that of adults. AB - Obesity in childhood is a very common disorder with an increasing prevalence. It is one of the most serious public health challenges. The objectives of the present paper are to increase the awareness of the problem of obesity in childhood, its serious complications and the need for prevention. Overweight and obese children are likely to remain obese into adulthood and more likely to develop serious complications including health problems such as diabetes and CVD, as well as psychological and social challenges. Overweight and obesity are largely preventable. In adults it is difficult to reduce excessive weight gain once it has become established, thus children should be considered the priority population for intervention strategies and prevention. Nutrition, exercise, weight gain in infancy, genetic and environmental factors, all contribute to the aetiology. Prevention and treatment of obesity in childhood requires education and empowerment of families relating to diet and exercise, along with the regulation and control of food marketing and clear nutritional labelling. The eating and physical activity behaviour of a child is strongly influenced by environmental and social factors. Therefore treatment will have only limited success in an environment where adequate physical activity is inhibited and the consumption of high-energy food is stimulated. Government investment in a health promotion programme addressing the issue of obesity in the population as a whole, with particular emphasis on the prevention and management of obesity in childhood is vital. The family doctor and multidisciplinary team play an important role. Regular visits to the family doctor, including growth assessment, will help motivate the family to restrict energy intake and to increase exercise. Therefore the prevention of childhood obesity needs high priority. PMID- 25115346 TI - Deficits in visuo-spatial but not in topographical memory during pregnancy and the postpartum state in an expert military pilot: a case report. AB - BACKGROUND: It is well known that cognitive and emotional changes occur during pregnancy, but little is known about their magnitude or their time of occurrence and recovery. During pregnancy memory is one of the most impaired cognitive functions. Although long-term aspects of memory have been investigated, other aspects of memory have not yet been explored (i.e., navigational memory and reaching memory). CASE PRESENTATION: Here we describe the changes in reaching and walking memory that occurred during pregnancy and one year after delivery in an Italian female military pilot (Case 1) with high spatial ability. In memory tests she showed a classical dissociation between performance in reaching and walking distance, which indicated a failure of working memory, learning, and storage in reaching space. This suggests that her expertise served as a protective factor mitigating her low walking memory performance, and saving the topographical component.We compared her performance with that of two non-pregnant control groups (i.e., women pilots and non-pilots) and found that Case 1's reaching memory performance was significantly worse than that of the control groups. Even one year postpartum, Case 1's performance was not yet the same as that of the other pilots. CONCLUSIONS: These findings contribute to our knowledge of the specific, as yet unexplored, aspects of memory deficits in women pilots during pregnancy and postpartum and suggest the need for better neuropsychological assessment before these women return to work in operational environments. PMID- 25115347 TI - The Effect of Ankle Taping to Restrict Plantar Flexion on Ball and Foot Velocity During an Instep Kick in Soccer. AB - CONTEXT: Posterior ankle impingement syndrome is a common disorder in soccer players and ballet dancers. In soccer players, it is caused by the repetitive stress of ankle plantar flexion due to instep kicking. Protective ankle dorsiflexion taping is recommended with the belief that it prevents posterior ankle impingement. However, the relationship between ankle taping and ball kicking performance remains unclear. OBJECTIVE: To demonstrate the relationship between the restrictions of ankle taping and performance of an instep kick in soccer. DESIGN: Laboratory-based repeated-measures. SETTING: University laboratory. PARTICIPANTS: 11 male university soccer players. INTERVENTION: The subjects' ankle plantar flexion was limited by taping. Four angles of planter flexion (0 degrees , 15 degrees , 30 degrees , and without taping) were formed by gradation limitation. The subjects performed maximal instep kicks at each angle. MAIN OUTCOME MEASURES: The movements of the kicking legs and the ball were captured using 3 high-speed cameras at 200 Hz. The direct linear-transformation method was used to obtain 3-dimensional coordinates using a digitizing system. Passive ankle plantar-flexion angle, maximal plantar-flexion angle at ball impact, ball velocity, and foot velocity were measured. The data were compared among 4 conditions using repeated-measures ANOVA, and the correlations between ball velocity and foot velocity and between ball velocity and toe velocity were calculated. RESULTS: Ankle dorsiflexion taping could gradually limit both passive plantar flexion and plantar flexion at the impact. Furthermore, limitation of 0 degrees and 15 degrees reduced the ball velocity generated by instep kicks. CONCLUSION: Plantar-flexion-limiting taping at 30 degrees has a potential to prevent posterior ankle impingement without decreasing the ball velocity generated by soccer instep kicks. PMID- 25115349 TI - Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state. AB - The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent upon the volumes and distribution of gastric and small intestinal water. However, little is known about the time courses and distribution of water volumes in vivo in an undisturbed gut. Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 +/- 7 mL (mean +/- SEM) of resting water. Upon drinking, the gastric fluid rose to 242 +/- 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T50%) of 13 +/- 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 +/- 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 +/- 24 mL contained within 15 +/- 2 pockets of 6 +/- 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 +/- 15 mL distributed into 16 +/- 3 pockets of 5 +/- 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds. PMID- 25115350 TI - Commentary on highlighted late breaking trials in interventional cardiology at ESC, VIVA, TCT, and AHA 2013. AB - With the plethora of clinical trials, it is difficult for busy interventional cardiologists to stay up to date. Therefore, the SCAI publications committee concisely summarizes and provides editorial commentary on the most important trials from recent, large international meetings. The intent is to provide this summary every six months to allow quick assimilation of trial results into interventional practice. (c) 2014 Wiley Periodicals, Inc. PMID- 25115352 TI - Effects of washing of the face with a mild facial cleanser formulated with sodium laureth carboxylate and alkyl carboxylates on acne in Japanese adult males. AB - BACKGROUND/PURPOSE: Washing the face with a mild cleanser is generally recommended for acne care. Occasionally, the general public has the misconception that acne is exacerbated by cleansers and furthermore it has concerns about inducing skin irritation and xerosis by intensive washing. Recently, we developed a new cleanser based on sodium laureth carboxylate and alkyl carboxylates (AEC/soap) that cleans sebum well without penetrating the stratum corneum. METHODS: We designed a controlled clinical trial conducted on adult Japanese males with moderate or less acne. Twenty subjects washed their faces with AEC/soap base cleanser twice a day for 4 weeks. Assessment of the efficacy was conducted prior to the start of the study, and at the end of weeks 2 and 4. RESULTS: Significant improvement of the acne was observed within 2 weeks, and acne lesions were not detectable in 25% of the subjects at week 4. Sebum secretion levels on the skin significantly increased on the forehead, but significantly decreased on the cheek which correlated with the improvement. No complaints of dryness or irritation occurred during the study. CONCLUSION: Washing the face twice a day with facial cleanser based on AEC/soap is an effective care for moderate or less grade facial acne. PMID- 25115351 TI - Proteomics-based metabolic modeling and characterization of the cellulolytic bacterium Thermobifida fusca. AB - BACKGROUND: Thermobifida fusca is a cellulolytic bacterium with potential to be used as a platform organism for sustainable industrial production of biofuels, pharmaceutical ingredients and other bioprocesses due to its capability of potential to convert plant biomass to value-added chemicals. To best develop T. fusca as a bioprocess organism, it is important to understand its native cellular processes. In the current study, we characterize the metabolic network of T. fusca through reconstruction of a genome-scale metabolic model and proteomics data. The overall goal of this study was to use multiple metabolic models generated by different methods and comparison to experimental data to gain a high confidence understanding of the T. fusca metabolic network. RESULTS: We report the generation of three versions of a metabolic model of Thermobifida fusca sp. XY developed using three different approaches (automated, semi-automated, and proteomics-derived). The model closest to in vivo growth was the proteomics derived model that consists of 975 reactions involving 1382 metabolites and account for 316 EC numbers (296 genes). The model was optimized for biomass production with the optimal flux of 0.48 doublings per hour when grown on cellobiose with a substrate uptake rate of 0.25 mmole/h. In vivo activity of the DXP pathway for terpenoid biosynthesis was also confirmed using real-time PCR. CONCLUSIONS: iTfu296 provides a platform to understand and explore the metabolic capabilities of the actinomycete T. fusca for the potential use in bioprocess industries for the production of biofuel and pharmaceutical ingredients. By comparing different model reconstruction methods, the use of high-throughput proteomics data as a starting point proved to be the most accurate to in vivo growth. PMID- 25115353 TI - KCNJ11 E23K variant is associated with the therapeutic effect of sulphonylureas in Chinese type 2 diabetic patients. AB - The aim of the present study was to investigate the effect of the E23K variant of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene on gliclazide modified release (MR) treatment in newly diagnosed patients with type 2 diabetes mellitus (T2DM). A total of 108 diabetic patients with no history of antidiabetic medication was treated with gliclazide MR for 16 weeks and underwent follow up at Weeks 2, 4, 8, 12 and 16. All patients were genotyped for KCNJ11 E23K (rs5219). At baseline, patients with the KK genotype had higher blood glucose and lower serum insulin levels after oral glucose administration than patients with the EE and EK genotypes (P < 0.05 for all). During treatment, individuals with the KK genotype had lower fasting glucose levels and were more likely to attain the target fasting glucose level (Plog rank = 0.028) than E allele carriers. Patients with the KK genotype had larger augmentations in changes (Delta) in acute insulin response (P = 0.049) and Delta body mass index (P = 0.003). Moreover, patients with the EK genotype had a lower variance in changes in fasting insulin levels (P = 0.049) and homeostasis model assessment of beta-cell function (P = 0.021) than those with the KK genotype. The findings of the present study suggest that the KCNJ11 E23K variant is associated with a greater effect of sulphonylurea treatment in newly diagnosed Chinese patients with T2DM. PMID- 25115355 TI - Locking versus non-locking plate fixation in the management of mandibular fractures: a meta-analysis. AB - The aim of the present study was to test whether there is a significant difference in the clinical outcomes between locking and non-locking plate fixation in the management of mandibular fractures. An electronic search without time or language restrictions was undertaken in December 2013. Eligible studies were clinical human studies, either randomized or not. The search strategy identified 10 publications. The I(2) statistic was used to express the percentage of the total variation across studies due to heterogeneity. The inverse variance method was used for the random-effects model in the case of heterogeneity being detected, or the fixed-effects model in the case of heterogeneity not being detected. The estimates of an intervention were expressed as the risk ratio (RR) with 95% confidence interval. Eight studies were judged to be at high risk of bias, whereas two studies were considered at moderate risk of bias. There was no statistically significant effect on the outcome of postoperative infection (P=0.17), malocclusion (P=0.15), hardware failure (P=0.77), hardware removal (P=0.95), wound dehiscence (P=0.98), or paraesthesia (P=0.20) in favour of locking plate fixation. The test for overall effect showed that the difference between the procedures did not significantly affect the incidence of postoperative complications (P=0.21), with RR 0.79 (95% CI 0.54-1.14). PMID- 25115354 TI - Evaluation of the measurement properties of the Manchester foot pain and disability index. AB - BACKGROUND: The Manchester Foot Pain and Disability Index (MFPDI, 19 items) was developed to measure functional limitations, pain and appearance for patients with foot pain and is frequently used in both observational studies and randomised controlled trials. A Dutch version of the MFPDI was developed. The aims of this study were to evaluate all the measurement properties for the Dutch version of the MFPDI and to evaluate comparability to the original version. METHOD: The MFPDI was translated into Dutch using a forward/backward translation process. The dimensionality was evaluated using exploratory and confirmatory factor analysis. Measurement properties were evaluated per subscale according to the COSMIN taxonomy consisting of: reliability (internal consistency, test-retest reliability and measurement error), validity (structural validity, content validity and cross-cultural validity comparing the Dutch version to the English version) responsiveness and interpretation. RESULTS: The questionnaire consists of three scales, measuring foot function, foot pain and perception. The reliability of the foot function scale is acceptable (Cronbach's alpha > 0.7, ICC = 0.7, SEM = 2.2 on 0-18 scale). The construct validity of the function and pain scale was confirmed and only the pain scale contains one item with differential item functioning (DIF). The responsiveness of the function and pain scale is moderate when compared to anchor questions. CONCLUSION: Results using the Dutch MFPDI version can be compared to results using the original version. The foot function sub-scale (items 1-9) is a reliable and valid sub-scale. This study indicates that the use of the MFPDI as a longitudinal instrument might be problematic for measuring change in musculoskeletal foot pain due to moderate responsiveness. PMID- 25115356 TI - Eosinophilic leukocytoclastic vasculitis - a spectrum ranging from Wells' syndrome to Churg-Strauss syndrome? AB - BACKGROUND: Wells' syndrome is defined as an inflammatory disorder with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Eosinophilic leukocytoclastic vasculitis shows eosinophilic infiltrates in combination with vasculitic changes. And Churg Strauss Syndrome comprises all three characteristics - eosinophilic infiltrates, vasculitis and flame figures. OBJECTIVE: To determine whether these three diseases are distinct entities or different manifestations of a similar clinicopathologic process. METHOD: Histopathological samples and clinical courses of 17 patients with eosinophilic infiltrates, flame figures and clinical features of Wells' syndrome were re-evaluated. Histopathologically, we focused on the presence or absence of vasculitic features. Clinically, we included only patients who were diagnosed with Wells' syndrome at least once in the course of their disease. RESULTS: 4 patients were finally diagnosed with Wells' syndrome, 5 with eosinophilic leukocytoclastic vasculitis and 6 with Churg Strauss syndrome. Further, we had one case of an overlap between Wells' syndrome and eosinophilic vasculitis and one case of Wegener granulomatosis. Vasculitic features were found in the samples of all patients. CONCLUSIONS: Histologically, we find vasculitic features in typical presentations of Wells' syndrome. Clinically, we find typical features of Wells' syndrome in patients finally diagnosed with eosinophilic leukocytoclastic vasculitis or Churg Strauss syndrome. Furthermore, we have observed and formerly reported 3 patients with progression from Wells' syndrome to Churg Strauss syndrome. Thus, we assume that eosinophilic leukocytoclastic vasculitis might form a bridge between Wells' syndrome and Churg Strauss syndrome. PMID- 25115357 TI - Room-temperature direct alkynylation of arenes with copper acetylides. AB - C-H bond in azoles and polyhalogenated arenes can be smoothly activated by copper acetylides to give the corresponding alkynylated (hetero)arenes by simple reaction at room temperature in the presence of phenanthroline and lithium tert butoxide under an oxygen atmosphere. These stable, unreactive, and readily available polymers act as especially efficient and practical reagents for the introduction of an alkyne group to a wide number of arenes under remarkably mild conditions. PMID- 25115358 TI - Laparoscopic ureteral reimplantation underneath broad ligament tunnel for female vesicoureteral stenosis: a technical innovation. AB - INTRODUCTION: In order to anatomically reconstruct ureteral stenosis, we present a novel technique for laparoscopic ureteral reimplantation. PATIENTS AND METHODS: Three young females, who were diagnosed with hydroureteronephrosis caused by congenital vesicoureteral junction obstruction, were treated by laparoscopic ureteral reimplantation with a tunnel underneath the broad ligament. RESULTS: Surgery was performed successfully without conversion to open surgery. No major intra- or postoperative complications occurred. Postoperative follow-up was 38, 33 and 26 months, respectively. The operative time was between 220 and 260 min. The mean estimated blood loss was less than 20 ml. Subsequent imaging performed 3 months after surgery revealed relief of hydroureteronephrosis for all patients. The patients all gave birth to healthy neonates and showed normal urinary tract sonogram and urine analysis during the gestation period. CONCLUSION: Laparoscopic ureteral reimplantation with broad ligament tunnel is safe and effective, allowing for anatomical reconstruction of ureter defects. However, a larger clinical sample and longer follow-up period will be needed. PMID- 25115359 TI - Endoscopic management of high-grade dysplastic Barrett's esophagus with esophageal varices. PMID- 25115361 TI - Needle confocal microendoscopy of a pancreatic neuroendocrine tumor. PMID- 25115360 TI - Prevalence and risk factors for musculoskeletal injuries related to endoscopy. AB - BACKGROUND: There are limited data regarding work-related injury among endoscopists. OBJECTIVE: To define the prevalence of endoscopy-related musculoskeletal injuries and their impact on clinical practice and to identify physician and practice characteristics associated with their development. DESIGN: Survey. SETTING: Electronic survey of active members of the American Society for Gastrointestinal Endoscopy with registered e-mail addresses. PARTICIPANTS: Physicians who currently or ever performed endoscopy and responded to the survey between February 2013 and November 2013. INTERVENTION: A 25-question, self administered, electronic survey. MAIN OUTCOME MEASUREMENTS: Prevalence, location, and ramifications of work-related injuries and endoscopist characteristics and workload parameters associated with endoscopy-related injury. RESULTS: The survey was completed by 684 endoscopists. Of those, 362 (53%) experienced a musculoskeletal injury perceived definitely (n = 204) or possibly (n = 158) related to endoscopy. Factors associated with a higher rate of endoscopy-related injury included higher procedure volume (>20 cases/week; P < .001), greater number of hours per week spent performing endoscopy (>16 hours/week; P < .001), and total number of years performing endoscopy (P = .004). The most common sites of injury were neck and/or upper back (29%) and thumb (28%). Only 55% of injured endoscopists used practice modifications in response to injuries. Specific treatments included medications (57%), steroid injection (27%), physiotherapy (45%), rest (34%), splinting (23%), and surgery (13%). LIMITATIONS: Self-reported data of endoscopy-related injury. CONCLUSION: Among endoscopists there is a high prevalence of injuries definitely or potentially related to endoscopy. Higher procedure volume, more time doing endoscopy per week, and cumulative years performing endoscopy are associated with more work-related injuries. PMID- 25115362 TI - Antegrade biopsy by using a trans-catheter technique through EUS-guided hepaticojejunostomy. PMID- 25115363 TI - Magnetic resonance enterography, small-intestine contrast US, and capsule endoscopy to evaluate the small bowel in pediatric Crohn's disease: a prospective, blinded, comparison study. AB - BACKGROUND: Small-bowel (SB) disease is a severe clinical entity among the phenotypes of Crohn's disease (CD). OBJECTIVE: To assess sensitivity, specificity, and accuracy of magnetic resonance enterography (MRE), small intestine contrast US (SICUS), and capsule endoscopy (CE) in the diagnosis of pediatric SB-CD. DESIGN: Prospective, blinded, comparison study. SETTING: Tertiary center for pediatric inflammatory bowel disease. PATIENTS: Children with known or suspected CD. Diagnosis of SB obstruction at SICUS or MRE excluded patients from the study. INTERVENTION: Patients underwent ileocolonoscopy, MRE, SICUS, and CE over a 7-day period. For the imaging evaluation, SB was divided into 3 segments: jejunum, proximal and mid ileum, and terminal ileum. MAIN OUTCOME MEASUREMENTS: The performance of each method was compared to a consensus reference standard for upper SB and to ileocolonoscopy for the terminal ileum. RESULTS: Twenty-five patients completed the study. In the jejunum, the sensitivity of SICUS and CE was 92%, which was not significantly higher than MRE (75%); the specificity of CE (61%) was significantly lower than that of MRE (P = .04). In the proximal and mid ileum, MRE and CE did not have significantly higher sensitivity (100%) than SICUS (80%), but CE was less specific (P > .05). At the terminal ileum, SICUS and MRE were slightly more sensitive than CE (94% vs. 81%); however, the latter was more specific. LIMITATIONS: Use of the consensus reference standard for upper SB. Small number of patients. CONCLUSION: SICUS, MRE, and CE are all effective options for imaging SB. An integrated use of different tools should be suggested to achieve a complete assessment of the SB in children with suspected or confirmed CD. PMID- 25115364 TI - The Educational Needs of Clinicians Regarding Anticoagulation Therapy for Prevention of Thromboembolism and Stroke in Patients With Atrial Fibrillation. AB - The objective is to identify practice patterns and attitudes of and barriers faced by US physicians assessing thromboembolism/stroke risk and managing anticoagulation in atrial fibrillation (AF) to determine educational needs. Case based surveys were used to assess practice patterns, guideline use, barriers, and attitudes; 51 cardiologists and 50 primary care physicians (PCPs) were surveyed. Most cardiologists use validated risk scoring systems to assess thromboembolism/stroke risk, and more than half of PCPs use clinical experience. Assessment of bleeding risk varied; more than half of respondents rely on clinical judgment or patient bleeding history. The most commonly used prophylactic agents are warfarin/another vitamin K antagonist (PCPs) or antiplatelet agents (cardiologists). Newer anticoagulants are used less frequently. Bleeding risk, need for frequent monitoring (vitamin K antagonists), and medication costs were the most significant barriers. Cardiologists and PCPs could benefit from education on validated scoring systems to assess risk of thromboembolism/stroke and bleeding in AF, on newly released AF guidelines, and on newer anticoagulants. PMID- 25115366 TI - Cage-like effect in Au-Pt nanoparticle synthesis in microemulsions: a simulation study. AB - The different distributions of metals in bimetallic nanoparticles synthesized in microemulsions were studied by computer simulation. The simulations demonstrated that if the difference between the reduction potentials of both metals is about 0.15-0.3 V, the compartmentalization of the reaction media causes the accumulation of slower reduction reactants in the microemulsions droplets, which favours the chemical reaction like a cage effect: increasing the local concentration of the slower reduction metal salt gives rise to a faster reduction, so the differences in reduction rates of both metals are attenuated. A more coincidental reduction of both metals deeply affects the nanoparticle structure, causing a better mixed alloy. This effect will be more pronounced when the concentration is higher and the intermicellar exchange rate is faster. This means that for any fixed microemulsion the nanoparticle structure can be modified by changing the reactant concentration: the core can be enriched in the faster reduction metal by lower concentrations, and the shell can be enriched in the slower metal by higher concentrations. Based on these observations, this study suggests a route to help experimentalists better create nanoparticles with a pre defined structure. PMID- 25115365 TI - Investigation of the role of organic cation transporter 2 (OCT2) in the renal transport of guanfacine, a selective alpha2A-adrenoreceptor agonist. AB - 1. Guanfacine is a selective alpha2A-adrenoreceptor agonist primarily excreted as its unchanged form through urine in human. This study was to investigate the involvement of organic cation transporter 2 (OCT2) in the renal tubular secretion of guanfacine. 2. Transport of guanfacine was characterized using human embryonic kidney (HEK293) cells expressing human OCT2 (hOCT2). The inhibitory effect of cimetidine on guanfacine uptake was also examined. In addition, in vivo pharmacokinetic study was conducted in rats to assess the effects of cimetidine on the pharmacokinetics of guanfacine. 3. The accumulation of guanfacine in hOCT2 transfected HEK293 cells was both time- and concentration-dependent, and markedly higher than that in mock cells. The apparent Km and Vmax values of guanfacine uptake by hOCT2 were 96.19 +/- 7.49 MUM and 13.03 +/- 0.49 nmol/mg protein/min, respectively. Guanfacine transport mediated by hOCT2 was significantly inhibited by a typical OCT2 inhibitor cimetidine with an IC50 value of 93.82 +/- 1.13 MUM. Co-administration of cimetidine significantly decreased the plasma clearance (CLp) as well as the renal clearance (CLr) of guanfacine in rats in a dose dependent manner, resulting in a noticeable increase in the systemic exposure of guanfacine. 4. These results indicated that OCT2 may be involved in the renal disposition of guanfacine. PMID- 25115367 TI - A new comprehensive classification system for both lower and upper urinary tract dysfunction in patients with neurogenic bladder. PMID- 25115368 TI - Use of the Gail model and breast cancer preventive therapy among three primary care specialties. AB - BACKGROUND: Breast cancer is an issue of serious concern among women of all ages. The extent to which providers across primary care specialties assess breast cancer risk and discuss chemoprevention is unknown. METHODS: Cross-sectional web based survey completed by 316 physicians in internal medicine (IM), family medicine (FM), and gynecology (GYN) from February to April of 2012. Survey items assessed respondents' frequency of use of the Gail model and chemoprevention, and their attitudes behind practice patterns. Descriptive statistics were used to generate response distributions, and chi-squared tests were used to compare responses among specialties. RESULTS: The response rate was 55.0 % (316/575). Only 40% of providers report having used the Gail model (37% IM, 33% FM, 60% GYN) and 13% report having recommended or prescribed chemoprevention (9% IM, 8% FM, 30% GYN). Among providers who use the Gail model, a minority use it regularly in patients who may be at increased breast cancer risk. Among providers who have prescribed chemoprevention, most have done so five times or fewer. Lack of both time and familiarity were commonly cited barriers to use of the Gail score and chemoprevention. CONCLUSIONS: An overall minority of providers, most notably in FM and IM, use the Gail model to assess, and chemoprevention to decrease, breast cancer risk. Until providers are more consistent in their use of the Gail model (or other breast cancer risk calculator) and chemoprevention, opportunities to intervene in women at increased risk will likely continue to be missed. PMID- 25115370 TI - Introduction to special issue for World Association for Plastic Surgeons of Chinese Descent. PMID- 25115369 TI - Cumulative trauma and midlife well-being in American women who served in Vietnam: effects of combat exposure and postdeployment social support. AB - BACKGROUND AND OBJECTIVES: Research increasingly demonstrates that trauma exposure can have cumulative effects, yet much remains to be learned about effects of cumulative trauma, particularly regarding longer term adjustment. One such trauma, combat exposure, is insufficiently understood, especially for women, who are increasingly engaged in professional combat activities. DESIGN: The study comprised a cross-sectional survey assessing multiple aspects of current well being in women approximately 25 years after their service in Vietnam during the Vietnam War. METHODS: Participants were 1374 women (78% military and 22% nonmilitary; mean age = 59.7). This study investigated the relations between three separate categories of trauma exposure (childhood, adulthood, and combat) and well-being and examined whether perceived social support at return from Vietnam moderated the association between combat exposure and well-being. RESULTS: While both childhood and adulthood trauma exposure related to midlife well-being, combat exposure still uniquely predicted outcomes. Further, postdeployment perceived social support moderated the association of combat and well-being: recollected higher perceived social support at homecoming buffered participants from the links between combat exposure and well-being. CONCLUSIONS: These results may have important implications for interventions to reduce the impact of traumatic experiences, particularly in light of the increasing exposure of women to direct combat events. PMID- 25115371 TI - Hypertrophic scars and keloids in surgery: current concepts. AB - Hypertrophic scars and keloids remain a challenge in surgery. We appreciate that our understanding of the process at cellular and molecular level, profound as it is, when it comes to the clinical evidence much is left to be desired. Although the bench to bedside conundrum remains, the science of translational research calls for an even higher level of cooperation between the scientist and the clinician for the impetus to succeed.The clinicians alerted us to the possible theories in the pathogenesis of keloid formation, inter alia, the ischemia theory, mast cell theory, immune theory, transforming growth factor beta interaction, mechanical theory, and the melanocyte stimulating hormone theory. All of the above presupposed a stimulus that would result in an uncontrolled upregulation of collagen and extracellular matrix expression in the pathogenesis of the keloid. This bedside to bench initiative, as in true science, realized more ponderables than possibilities.By the same token, research into the epidermal-mesenchymal signaling, molecular biology, genomics, and stem cell research holds much promise in the bench top arena. To assess efficacy, many scar assessment scores exist in the literature. The clinical measurement of scar maturity can aid in determining end points for therapeutics. Tissue oxygen tension and color assessment of scars by standardized photography proved to be useful.In surgery, the use of dermal substitutes holds some promise as we surmise that quality scars that arise from dermal elements, molecular and enzyme behavior, and balance. Although a systematic review shows some benefit for earlier closure and healing of wounds, no such review exists at this point in time for the use of dermal substitutes in scars.Adipose-derived stem cell, as it pertains to scars, will hopefully realize the potential of skin regeneration rather than by repair in which we are familiar with as well as the undesirable scarring as a result of healing through the inflammatory response.Translational research will bear the fruit of coordinating bench to bedside and vice versa in the interest of progress into the field of regenerative healing that will benefit the patient who otherwise suffers the myriad of scar complications. PMID- 25115372 TI - Propranolol promotes accelerated and dysregulated adipogenesis in hemangioma stem cells. AB - BACKGROUND: Infantile hemangiomas (IHs) are the most common tumor of infancy, yet there are no Food and Drug Administration-approved therapeutics to date. Recently, the nonselective beta-adrenergic-blocker propranolol has been shown to be a safe and effective means of treating IHs, although its mechanism has yet to be elucidated. We have previously demonstrated that propranolol induces early and incomplete adipogenesis in stem cells derived from hemangiomas. We hypothesize that propranolol promotes dysregulated adipogenesis via the improper regulation of adipogenic genes. METHODS: Hemangioma stem cells (HemSCs) isolated from resected IH specimens were treated with adipogenic medium for 1 or 4 days in either propranolol or vehicle. Cell death was measured by the incorporation of annexin V and propidium iodide by flow cytometry. Adipogenesis was assessed by visualizing lipid droplet formation by Oil Red O staining. Proadipogenic genes C/EBPalpha, C/EBPbeta, C/EBPdelta, PPARdelta, PPARgamma, RXRalpha, and RXRgamma were analyzed by quantitative reverse transcription and polymerase chain reaction. RESULTS: Hemangioma stem cells treated with propranolol increased lipid droplet formation compared to vehicle-treated cells indicating increased adipogenesis. Cell death as measured by FACS analysis indicated that the propranolol-treated cells died due to necrosis and not apoptosis. During adipogenesis, transcript levels of PPARdelta, PPARgamma, C/EBPbeta, and C/EBPdelta were significantly increased (P<0.01) in propranolol-treated cells relative to control cells. In contrast, RXRalpha and RXRgamma levels were significantly decreased (P<0.05), and C/EBPalpha, a gene required for terminal adipocyte differentiation, was strongly suppressed by propranolol when compared to vehicle-treated cells (P<0.01). CONCLUSIONS: In HemSCs, propranolol accelerated dysregulated adipogenic differentiation characterized by improper adipogenic gene expression. Consistent with accelerated adipogenesis, propranolol significantly increased the expression of the proadipogenic genes, PPARgamma, C/EBPbeta, and C/EBPgamma compared to control. However, propranolol treatment also led to improper induction of PPARdelta and suppression of C/EBPalpha, RXRalpha, and RXRgamma. Taken together these data indicate that propranolol promoted dysregulated adipogenesis and inhibited the HemSCs from becoming functional adipocytes, ultimately resulting in cell death. Understanding this mechanism behind propranolol's effectiveness will be a vital factor in producing more effective therapies in the future. PMID- 25115373 TI - Simultaneous breast reconstruction and treatment of breast cancer-related upper arm lymphedema with lymphatic lower abdominal flap. AB - BACKGROUND: This study was designed to introduce the key points about the transplantation of lower abdominal flap with vascularized lymph node and to evaluate the effect of breast restoration, breast reconstruction, and lymphatic transplantation to treat upper limb lymphedema after breast cancer surgery. MATERIALS AND METHODS: The study was based on the retrospective study on 10 cases of postmastectomy lymphedema during January 2008 to March 2011. All patients, aged 36 to 50 years, have had one-side upper-limb lymphedema for 3 to 5 years. Six patients had accepted radiotherapy. Four patients had a diagnosis of severe lymphedema, and 2 patients had moderate lymphedema. The isotope radiography before the operation showed obstruction of lymphatic return, and the multidetector computed tomography that followed delivered a clear picture of the abdominal flap blood supply and the blood vessels in the breasts. During the operation, the scar contracture of the axilla was completely relaxed, and all patients accepted abdominal transplantation of lower abdominal flap with vascularized lymph node. After the operation, the elastic bandages were applied for one year as an adjuvant therapy. The follow-up visits were conducted 1, 3, 6, and 12 months after the surgery. The measurement indexes included mid-upper arm circumference, clinical symptoms, and lymphoscintigraphy. RESULTS: All flaps worked well. One patient was found to have delayed wound healing; one patient saw no obvious improvement in lymphedema; 7 patients with lymphedema were relieved with apparent improvement in the affected limbs' mean perimeter and clinical symptoms; one patient recovered; and another patient was lost to follow-up. The mean reduction was 2.122+/-2.331 cm, and the reduction of the lymphedematous limb was statistically significant between the preoperative and 12-month postoperative groups (P<0.05). The results were good in 4 patients and excellent in one patient. CONCLUSIONS: The transplantation of abdominal flap with vascularized lymph node and breast reconstruction, accompanied by the treatment to upper limb lymphedema and using elastic bandages as an adjuvant therapy, is considered to be an effective method to restore the configuration and function of breasts. Long term follow-up visits are undergoing, especially the lymphoscintigraphy, 2 years after the operation. PMID- 25115374 TI - Reconstruction for osteoradionecrosis of the mandible: superiority of free iliac bone flap to fibula flap in postoperative infection and healing. AB - BACKGROUND: Osteoradionecrosis (ORN) of the mandible is not an uncommon complication after radiotherapy for head and neck cancers. Although definitive treatment has been confirmed as radical excision of the necrotic bone with simultaneous vascularized osteocutaneous flap reconstruction, it remains a unique challenge. In this study, we compare our results of reconstruction with free iliac and fibula flaps in flap survival, bony union, and postoperative complications. PATIENTS AND METHODS: From 1986 to 2011, there were 153 mandibular ORN cases in our center that were treated with radical resection of the necrotic bone and reconstruction with either vascularized iliac (n=108) or fibula flaps (n=45). Data collected for analysis included patient demographics, flap survival rate, postoperative infection rate, nonunion/malunion rate, mean hospital stay, and antibiotics use. RESULTS: All patients healed eventually without recurrence of ORN. However, we observed difference in the complication rate between the iliac flap group and fibula flap group. In the group with iliac flap reconstruction, patients required less days of hospital stay for intravenous antibiotics treatment postoperatively. The average days required for intravenous antibiotics in the iliac flap group were 10.46 (2.28) versus 16.09 (3.88) days in the fibula group (P<0.01). In the group with fibula flap reconstruction, 9 (20.0%) patients had subsequent neck infection due to healing problem, compared to 8 (7.4%) patients in the iliac flap group (P=0.04). In the iliac flap group, the nonunion and malunion rates were 4.6% and 2.8% respectively; whereas in the fibula group, the rates were 15.5% and 6.6%, respectively (P=0.04 and 0.36, respectively). CONCLUSIONS: For ORN patients, vascularized iliac bone flap provides more reliable results compared to fibula flap. The merits of vascularized iliac flap include the following: (1) its natural curve mimics the shape of mandible and does not need osteotomy; (2) it offers more volume of bone that matches better to the native mandible to allow later osteointegration as well as faster bony union, due to the nature of being a membranous bone; and (3) it carries more abundant soft tissue to obliterate possible dead space. The only disadvantages are short pedicle and requiring special management of skin paddle, which can be overcome by training in microsurgery. PMID- 25115375 TI - Penile reconstruction by preexpanded free scapular flap in severely burned patient. AB - BACKGROUND: Penile reconstruction or phalloplasty has always been one of the most challenging problems for plastic surgeons. In 1936, Bogoras performed the first phalloplasty by using traditional tubed pedicle flaps. Many other flaps and methods have been applied since, including lower abdominal flaps, pudendal-thigh flaps, parascapular flaps, paraumbilical flaps and, of course, radial forearm flaps. For each method, reports of both functional and esthetic successes abound. In this case, donor sites for phalloplasty were somewhat limited by the severe electric burn injury. After much consideration, we decided to preexpand the scapular flap and to use this for phalloplasty, with satisfactory outcome. Our case is a 31-year-old patient who sustained a 19% total burn surface area by electrical burn in August 2011. The burn area involved both forearms, abdominal region, both femoral regions, and perineum including genitalia loss. Most of the burn wounds were skin grafted shortly after the injury. Due to the nature of the burn, regular donor sites for penile reconstruction were unavailable. Before surgery, we went through a detailed plan for phalloplasty with the patient and his family. The patient consented to the 2-stage surgery for the penile reconstruction. The first stage was insertion of a 600-mL soft tissue expander in the scapular region. After 4 months of expansion, the second stage of free scapular flap transfer was performed in March 2012. RESULTS: The reconstruction was successful with good appearance and patient satisfaction, complicated by urethral fistula. Eight months later, the urinary fistula was repaired successfully. CONCLUSIONS: The free scapular flap proved to be an ideal solution to this patient's dilemma. The flap has adequate amount of tissue and a reliable blood supply. Its amenability to be expanded allows better donor-site primary closure. Tissue bulk resulted in adequate stiffness without artificial prosthesis for the phallus to be functional. PMID- 25115376 TI - Angioarchitecture of extracranial arteriovenous malformations: a vascular casting study. AB - PURPOSE: Arteriovenous malformations (AVMs) are congenital vascular anomalies, not proliferative neoplasms, but tend to behave aggressively with unpredictable growth and tissue destruction. For the understanding of the angioarchitecture of extracranial AVM, which is believed to be the main cause that explains all presenting symptoms, the study aimed to elucidate the vascular structure of extracranial AVM with vascular cast of completely excised AVM lesion. METHODS: From 1996 to 2011, a total of 289 cases with extracranial AVM received surgical or surgery-based treatment by the authors in the department, excluding cases that received embolization alone. Among them, 10 patients (4 female cases, 6 male cases) were involved in this study. All the AVM nidi were excised and injected with resin through feeding arteries, then the corrosion casts were made for dimensional measurement. RESULTS: Arteriovenous malformation nidus was comprised of multilevel branched blood vessels. We measured the diameter of predominant trunk and primary level branch vessels. The diameter of predominant trunk ranged from 2.0 (0.2) to 4.3 (0.2) mm, whereas primary level branch vessels from 1.0 (0.1) to 2.0 (0.2) mm. Seventy percent of AVM casts included trunk blood vessels with the maximal diameters ranged from 4 to 12 mm, and an average of 7.0 mm (SD, 0.93; n=10). In this series, the smallest blood vessel visible in the cast was approximately 0.2 mm in diameter, whereas balloon-like serious dilated vessels from 10.2 to 25.4 mm. CONCLUSIONS: Vascular casting study shows us more informative, realistic, and objective 3-dimensional angioarchitecture than digital subtract angiography, 3-dimensional computed tomography angiography, and magnetic resonance angiography, not only for the facilitation of treatment decision but also for the purpose of education and research. PMID- 25115377 TI - Expansion method in secondary total ear reconstruction for undesirable reconstructed ear. AB - BACKGROUND: Ear reconstruction by autologous costal cartilage grafting is the most widely applied technique with fewer complications. However, undesirable ear reconstruction brings more problems to plastic surgeons. Some authors resort to free flap or osseointegration technique with prosthetic ear. In this article, we introduce a secondary total ear reconstruction with expanded skin flap method. METHODS: From July 2010 to April 2012, 7 cases of undesirable ear reconstruction were repaired by tissue expansion method. Procedures including removal of previous cartilage framework, soft tissue expander insertion, and second stage of cartilage framework insertion were performed to each case regarding their local conditions. RESULTS: The follow-up time ranged from 6 months to 2.5 years. All of the cases recovered well with good 3-dimensional forms, symmetrical auriculocephalic angle, and stable fixation. CONCLUSIONS: All these evidence showed that this novel expansion method is safe, stable, and less traumatic for secondary total ear reconstruction. With sufficient expanded skin flap and refabricated cartilage framework, lifelike appearance of reconstructed ear could be acquired without causing additional injury. PMID- 25115378 TI - Masseter-to-facial nerve transfer: a highly effective technique for facial reanimation after acoustic neuroma resection. AB - BACKGROUND: Masseter-to-facial nerve transfer is a new procedure for patients who acquire a proximal injury to the facial nerve. This article reports that this procedure is effective and associated with minimal morbidities. METHODS: From November 2010 to February 2013, 16 patients underwent a masseter-to-facial nerve transfer. Their denervation periods varied from 2 to 18 months, with an average of 10.1+/-4.1 months. Their ages varied from 22 to 70 years, with an average of 34.7+/-15.4 years. The etiology of denervation was tumor resection in the cerebellopontine angle in all cases. All of the patients were followed up several times. The outcomes of the first follow-up at 3 months postoperatively and the last follow-up at a minimum 12 months postoperatively were documented. Using Terzis' and Metha's scales, the smile outcomes and synkinetic movements as visualized using standardized videos were graded preoperatively and postoperatively. The periods between the operation and the onset of mimetic muscle contraction were documented. A questionnaire was administered to evaluate the donor-site morbidity and the ability to smile without biting. RESULTS: The final outcomes for smile function were as follows: 9 patients (56.3%) had excellent or good function, 5 patients (31.3%) had moderate function, and 2 patients (12.5%) had poor function. There was significant improvement between the preoperative and postoperative time points and between the outcomes at the first and last follow-ups (P<0.05). Additionally, 13 (81.3%) patients had the ability to smile without biting 12 months postoperatively. The onset of muscle motion varied from 56 to 365 days and was positively correlated with age in the group of patients older than 40 years and negatively correlated with the outcome of the first follow-up. Four (25%) patients complained of concavity at the parotideomasseteric region, but none complained of disturbance in food intake. Synkinetic movements were observed in all patients and were rated as mild. CONCLUSIONS: The masseter-facial nerve transfer effectively reanimated the paralytic muscle in patients who acquired an intracranial facial nerve injury with minimal deficits at the donor site. After continued physical therapy, some patients were able to regain a symmetrical and effortless smile with mild synkinetic movements. PMID- 25115380 TI - Clinical phenotype network: the underlying mechanism for personalized diagnosis and treatment of traditional Chinese medicine. AB - Traditional Chinese medicine (TCM) investigates the clinical diagnosis and treatment regularities in a typical schema of personalized medicine, which means that individualized patients with same diseases would obtain distinct diagnosis and optimal treatment from different TCM physicians. This principle has been recognized and adhered by TCM clinical practitioners for thousands of years. However, the underlying mechanisms of TCM personalized medicine are not fully investigated so far and remained unknown. This paper discusses framework of TCM personalized medicine in classic literatures and in real-world clinical settings, and investigates the underlying mechanisms of TCM personalized medicine from the perspectives of network medicine. Based on 246 well-designed outpatient records on insomnia, by evaluating the personal biases of manifestation observation and preferences of herb prescriptions, we noted significant similarities between each herb prescriptions and symptom similarities between each encounters. To investigate the underlying mechanisms of TCM personalized medicine, we constructed a clinical phenotype network (CPN), in which the clinical phenotype entities like symptoms and diagnoses are presented as nodes and the correlation between these entities as links. This CPN is used to investigate the promiscuous boundary of syndromes and the co-occurrence of symptoms. The small-world topological characteristics are noted in the CPN with high clustering structures, which provide insight on the rationality of TCM personalized diagnosis and treatment. The investigation on this network would help us to gain understanding on the underlying mechanism of TCM personalized medicine and would propose a new perspective for the refinement of the TCM individualized clinical skills. PMID- 25115379 TI - Phospholipid binding residues of eukaryotic membrane-remodelling F-BAR domain proteins are conserved in Helicobacter pylori CagA. AB - BACKGROUND: Cytotoxin associated gene product A (CagA) is an oncogenic protein secreted by the gastric bacterium Helicobacter pylori. Internalization of CagA by human epithelial cells occurs by an unknown mechanism that requires interaction with the host membrane lipid phosphatidylserine. FINDINGS: Local homology at the level of amino acid sequence and secondary structure has been identified between the membrane-tethering region of CagA and the lipid-binding Fes-CIP4 homology Bin/Amphiphysin/Rvs (F-BAR) domains of eukaryotic proteins. The F-BAR proteins are major components of the endocytic machinery. In addition to the membrane binding F-BAR domains, they contain other domains that interact with actin regulatory networks and mediate interplay between membrane dynamics and cytoskeleton re-arrangements. Positively charged residues found on the lipid binding face of the F-BAR domains are conserved in CagA and represent residues involved in CagA binding to lipids. CONCLUSIONS: The homologies with F-BAR proteins extend to lipid binding specificities and involvement in reorganization of the actin cytoskeleton. CagA and F-BAR domains share binding specificity for phosphatidylserine and phosphoinositides. Similar to the F-BAR proteins, CagA has a membrane-binding module and a module that shares structural homology with actin binding proteins, and, like eukaryotic F-BAR domain proteins, CagA function is linked to actin dynamics. The uncovered similarities between the bacterial effector protein and eukaryotic F-BAR proteins suggest convergent evolution of CagA towards a similar function. PMID- 25115381 TI - In vivo evaluation of two forms of urea in the skin by Raman spectroscopy after application of urea-containing cream. AB - BACKGROUND/PURPOSE: As urea is one of the natural moisturizing factor (NMF) components in the stratum corneum, it has been used in topical products to improve skin conditions. However, the penetration behavior of urea in the skin after application of urea-containing cream has not been determined as there has been no technique with which to measure the urea content in the skin in vivo non invasively. We therefore applied Raman spectroscopy to evaluate the depth profile of urea content in the skin. We investigated changes in depth profiles of two forms of urea to evaluate the penetration behavior of urea after application of urea-containing cream. METHODS: Commercially available moisturizing creams F and R in quantities of 2.2-mg/cm(2) and containing 20% (w/w) urea were applied to volar forearm skin of six Japanese subjects. Raman spectra of the skin were measured at 2-MUm intervals from the skin surface toward the interior using a confocal Raman spectrometer (model 3510 SCA) before and 15, 60, and 120 min after the application of the creams. The amounts of the two forms of urea, urea in water solution and urea in a solid state, were calculated by adding the spectra of solid urea and the cream base to a previously reported algorithm including the spectrum of urea in water solution. RESULTS: The characteristic band of urea in water solution was observed at approximately 1004/cm and that of the solid state at approximately 1010/cm in the Raman spectra of the skin after application of either cream. There was more urea in water solution form in the area where cream F was applied than in the area where cream R was applied. There was more urea in a solid state in the area where cream R was applied than in the area where cream F was applied at all depths and measurement times. In particular, there was significantly more urea in a solid state below a depth of 2 MUm in the area where cream R was applied than in the area where cream F was applied 15 min after application. CONCLUSION: The present study demonstrated that we can measure both urea forms in the skin after the application of urea-containing creams. The proposed technique would be useful in the evaluation of characteristics of the penetration behavior of urea in the skin after the application of various urea containing moisturizers. PMID- 25115383 TI - FGFR1 activation is an escape mechanism in human lung cancer cells resistant to afatinib, a pan-EGFR family kinase inhibitor. AB - Most NSCLC patients with EGFR mutations benefit from treatment with EGFR-TKIs, but the clinical efficacy of EGFR-TKIs is limited by the appearance of drug resistance. Multiple kinase inhibitors of EGFR family proteins such as afatinib have been newly developed to overcome such drug resistance. We established afatinib-resistant cell lines after chronic exposure of activating EGFR mutation positive PC9 cells to afatinib. Afatinib-resistant cells showed following specific characteristics as compared to PC9: [1] Expression of EGFR family proteins and their phosphorylated molecules was markedly downregulated by selection of afatinib resistance; [2] Expression of FGFR1 and its ligand FGF2 was alternatively upregulated; [3] Treatment with anti-FGF2 neutralizing antibody blocked enhanced phosphorylation of FGFR in resistant clone; [4] Both resistant clones showed collateral sensitivity to PD173074, a small-molecule FGFR-TKIs, and treatment with either PD173074 or FGFR siRNA exacerbated suppression of both afatinib-resistant Akt and Erk phosphorylation when combined with afatinib; [5] Expression of twist was markedly augmented in resistant sublines, and twist knockdown specifically suppressed FGFR expression and cell survival. Together, enhanced expression of FGFR1 and FGF2 thus plays as an escape mechanism for cell survival of afatinib-resistant cancer cells, that may compensate the loss of EGFR driven signaling pathway. PMID- 25115382 TI - HDAC inhibitors and immunotherapy; a double edged sword? AB - Epigenetic modifications, like histone acetylation, are essential for regulating gene expression within cells. Cancer cells acquire pathological epigenetic modifications resulting in gene expression patterns that facilitate and sustain tumorigenesis. Epigenetic manipulation therefore is emerging as a novel targeted therapy for cancer. Histone Acetylases (HATs) and Histone Deacetylases (HDACs) regulate histone acetylation and hence gene expression. Histone deacetylase (HDAC) inhibitors are well known to affect cancer cell viability and biology and are already in use for the treatment of cancer patients. Immunotherapy can lead to clinical benefit in selected cancer patients, especially in patients with limited disease after tumor debulking. HDAC inhibitors can potentially synergize with immunotherapy by elimination of tumor cells. The direct effects of HDAC inhibitors on immune cell function, however, remain largely unexplored. Initial data have suggested HDAC inhibitors to be predominantly immunosuppressive, but more recent reports have challenged this view. In this review we will discuss the effects of HDAC inhibitors on tumor cells and different immune cell subsets, synergistic interactions and possible mechanisms. Finally, we will address future challenges and potential application of HDAC inhibitors in immunocombination therapy of cancer. PMID- 25115384 TI - A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer. AB - Based on 108 differentially expressed genes between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts we recently reported, a 5-gene classifier for relapse prediction in Stage II/III colorectal cancer (CRC ) was developed. Its predictive value was validated in datasets GSE17538, GSE33113 and GSE14095. An additional validation was performed in a metacohort (n=317) and 142 CRC patients by means of RT-PCR. The 5-gene classifier was significantly associated with increased relapse risk and death from CRC across all validation series of Stage II/III patients used. Multivariate Cox regression analyses confirmed the independent prognostic value of the stromal classifier (HR=2.67; P=0.002). Post-test probabilities provided evidence of the suitability of the 5 gene classifier in clinical practice, identifying a subgroup of Stage-II patients who were at high risk of relapse. Moreover, the a priory worst prognosis mesenchymal subtype of tumours can be stratified according to the physiological status of their carcinoma-associated fibroblasts. In conclusion the CAFs-derived 5-gene classifier provides more accurate information about outcome than conventional clinicopathological criteria and it could be useful to take clinical decisions, especially in Stage II. Additionally, the classifier put into relevance the CAF's intratumoral heterogeneity and might contribute to find relevant targets for depleting adequate CAFS subtypes. PMID- 25115385 TI - T cell-recruiting triplebody 19-3-19 mediates serial lysis of malignant B lymphoid cells by a single T cell. AB - Triplebody 19-3-19, an antibody-derived protein, carries three single chain fragment variable domains in tandem in a single polypeptide chain. 19-3-19 binds CD19-bearing lymphoid cells via its two distal domains and primary T cells via its CD3-targeting central domain in an antigen-specific manner. Here, malignant B lymphoid cell lines and primary cells from patients with B cell malignancies were used as targets in cytotoxicity tests with pre-stimulated allogeneic T cells as effectors. 19-3-19 mediated up to 95 % specific lysis of CD19-positive tumor cells and, at picomolar EC50 doses, had similar cytolytic potency as the clinically successful agent Blinatumomab. 19-3-19 activated resting T cells from healthy unrelated donors and mediated specific lysis of both autologous and allogeneic CD19-positive cells. 19-3-19 led to the elimination of 70 % of CD19 positive target cells even with resting T cells as effectors at an effector-to target cell ratio of 1 : 10. The molecule is therefore capable of mediating serial lysis of target cells by a single T cell. These results highlight that central domains capable of engaging different immune effectors can be incorporated into the triplebody format to provide more individualized therapy tailored to a patient's specific immune status. PMID- 25115387 TI - Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations of cancer genes in blastic plasmacytoid dendritic cell neoplasm. AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1%), as well as in VHL, BRAF, MLH1, TP53 and RET1 (3% each). Moreover, NRAS-, KRAS- and ATM-mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored. PMID- 25115388 TI - The stress phenotype makes cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase. AB - CDT2/L2DTL/RAMP is one of the substrate receptors of the Cullin Ring Ubiquitin Ligase 4 that targets for ubiquitin mediated degradation a number of substrates, such as CDT1, p21 and CHK1, involved in the regulation of cell cycle and survival. Here we show that CDT2 depletion was alone able to induce the apoptotic death in 12/12 human cancer cell lines from different tissues, regardless of the mutation profile and CDT2 expression level. Cell death was associated to rereplication and to loss of CDT1 degradation. Conversely, CDT2 depletion did not affect non-transformed human cells, such as immortalized kidney, lung and breast cell lines, and primary cultures of endothelial cells and osteoblasts. The ectopic over-expression of an activated oncogene, such as the mutation-activated RAS or the amplified MET in non-transformed immortalized breast cell lines and primary human osteoblasts, respectively, made cells transformed in vitro, tumorigenic in vivo, and susceptible to CDT2 loss. The widespread effect of CDT2 depletion in different cancer cells suggests that CDT2 is not in a synthetic lethal interaction to a single specific pathway. CDT2 likely is a non-oncogene to which transformed cells become addicted because of their enhanced cellular stress, such as replicative stress and DNA damage. PMID- 25115386 TI - Cannabinoids as therapeutic agents in cancer: current status and future implications. AB - The pharmacological importance of cannabinoids has been in study for several years. Cannabinoids comprise of (a) the active compounds of the Cannabis sativa plant, (b) endogenous as well as (c) synthetic cannabinoids. Though cannabinoids are clinically used for anti-palliative effects, recent studies open a promising possibility as anti-cancer agents. They have been shown to possess anti proliferative and anti-angiogenic effects in vitro as well as in vivo in different cancer models. Cannabinoids regulate key cell signaling pathways that are involved in cell survival, invasion, angiogenesis, metastasis, etc. There is more focus on CB1 and CB2, the two cannabinoid receptors which are activated by most of the cannabinoids. In this review article, we will focus on a broad range of cannabinoids, their receptor dependent and receptor independent functional roles against various cancer types with respect to growth, metastasis, energy metabolism, immune environment, stemness and future perspectives in exploring new possible therapeutic opportunities. PMID- 25115389 TI - Identification of a gene expression driven progression pathway in myxoid liposarcoma. AB - AIM: to investigate the events involved in the progression of myxoid liposarcoma (MLS). Gene expression profiling and immunohistochemical/biochemical analyses were applied to specimens representative of the opposite ends of the MLS spectrum: pure myxoid (ML) and pure round cell (RC) liposarcomas. The analyses revealed the involvement of both coding and non coding RNAs (SNORDs located in DLK1-DIO3 region) and support a model of stepwise progression mainly driven by epigenetic changes involving tumour vascular supply and tumoral cellular component. In this model, a switch in the vascular landscape from a normal to a pro-angiogenic signature and the silencing of DLK1-DIO3 region mark the progression from ML to RC in concert with the acquisition by the latter of the over-expression of YYI/C-MYC/HDAC2, together with over-expression of genes involved in cell proliferation and stemness: MKNK2, MSX1 and TRIM71. Taken together, these findings strongly suggest that to progress from ML to RC liposarcoma the cells have to overcome the epigenetic silencing restriction point in order to reset their new stem-like differentiation signature. Our findings provide a first attempt at identifying the missing links between ML and RC liposarcomas, that may also have broader applications in other clinico pathological settings characterised by a spectrum of progression. PMID- 25115391 TI - 4EGI-1 targets breast cancer stem cells by selective inhibition of translation that persists in CSC maintenance, proliferation and metastasis. AB - Cancer death is a leading cause of global mortality. An estimated 14.1 million new cancer cases and 8.2 million cancer deaths occurred worldwide in 2012 alone. Cancer stem cells (CSCs) within tumors are essential for tumor metastasis and reoccurrence, the key factors of cancer lethality. Here we report that 4EGI-1, an inhibitor of the interaction between translation initiation factors eIF4E1 and eIF4G1 effectively inhibits breast CSCs through selectively reducing translation persistent in breast CSCs. Translation initiation factor eIF4E1 is significantly enhanced in breast CSCs in comparison to non-CSC breast cancer cells. 4EGI-1 presents increased cytotoxicity to breast CSCs compared to non-CSC breast cancer cells. 4EGI-1 promotes breast CSC differentiation and represses breast CSC induced tube-like structure formation of human umbilical vein endothelial cells (HUVECs). 4EGI-1 isomers suppress breast CSC tumorangiogenesis and tumor growth in vivo. In addition, 4EGI-1 decreases proliferation in and induces apoptosis into breast CSC tumor cells. Furthermore, 4EGI-1 selectively inhibits translation of mRNAs encoding NANOG, OCT4, CXCR4, c-MYC and VEGF in breast CSC tumors. Our study demonstrated that 4EGI-1 targets breast CSCs through selective inhibition of translation critical for breast CSCs, suggesting that selective translation initiation interference might be an avenue targeting CSCs within tumors. PMID- 25115390 TI - The role of homeostatic regulation between tumor suppressor DAB2IP and oncogenic Skp2 in prostate cancer growth. AB - Altered DAB2IP gene expression often detected in prostate cancer (PCa) is due to epigenetic silencing. In this study, we unveil a new mechanism leading to the loss of DAB2IP protein; an oncogenic S-phase kinase-associated protein-2 (Skp2) as E3 ubiquitin ligase plays a key regulator in DAB2IP degradation. In order to unveil the role of Skp2 in the turnover of DAB2IP protein, both prostate cell lines and prostate cancer specimens with a variety of molecular and cell biologic techniques were employed. We demonstrated that DAB2IP is regulated by Skp2 mediated proteasome degradation in the prostate cell lines. Further analyses identified the N-terminal DAB2IP containing the ubiquitination site. Immunohistochemical study exhibited an inverse correlation between DAB2IP and Skp2 protein expression in the prostate cancer tissue microarray. In contrast, DAB2IP can suppressSkp2 protein expression is mediated through Akt signaling. The reciprocal regulation between DAB2IP and Skp2 can impact on the growth of PCa cells. This reciprocal regulation between DAB2IP and Skp2 protein represents a unique homeostatic balance between tumor suppressor and oncoprotein in normal prostate epithelia, which is apparently altered in cancer cells. The outcome of this study has identified new potential targets for developing new therapeutic strategy for PCa. PMID- 25115392 TI - F-box protein FBXO31 is down-regulated in gastric cancer and negatively regulated by miR-17 and miR-20a. AB - FBXO31, a subunit of the SCF ubiquitin ligase, played a crucial role in neuronal development, DNA damage response and tumorigenesis. Here, we investigated the expression and prognosis value of FBXO31 in human primary gastric cancer (GC) samples. Meanwhile, the biological role and the regulation mechanism of FBXO31 were evaluated. We found that FBXO31 mRNA and protein was decreased dramatically in the GC tissue compared with the adjacent non-cancerous tissues. FBXO31 expression was significantly associated with tumor size, tumor infiltration, clinical grade and patients' prognosis. FBXO31 overexpression significantly decreased colony formation and induced a G1-phase arrest and inhibited the expression of CyclinD1 protein in GC cells. Further evidence was obtained from knockdown of FBXO31. Ectopic expression of FBXO31 dramatically inhibited xenograft tumor growth in nude mice. miR-20a and miR-17 mimics inhibited, whereas the inhibitor of miR-20a and miR-17 increased, the expression of FBXO31, respectively. miR-20a and miR-17 directly bind to the 3'-UTR of FBXO31. The level of miR-20a and miR-17 in GC tissue was significantly higher than that in surrounding normal mucosa. Moreover, a highly significant negative correlation between miR-20a (miR-17) and FBXO31 was observed in these GC samples. Therefore, effective therapy targeting the miR-20a (miR-17)-FBXO31-CyclinD1 pathway may help control GC progression. PMID- 25115394 TI - Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression. AB - MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20 tubular adenomas, 50 colorectal carcinoma (CRC), and 40 CRC liver metastases. Control samples obtained from patients with irritable bowel syndrome, or tumor matched normal colon mucosa were analyzed (n=50). MiR-182 expression increased progressively and significantly along with the colorectal carcinogenesis cascade, and in CRC liver metastases. The inverse relation between miR-182 and the expression of its target gene ENTPD5 was investigated by immunohistochemical analysis. We observed that normal colocytes featured a strong ENTPD5 cytoplasmic expression whereas a significantly and progressively lower expression was present along with dedifferentiation of the histologic phenotype. Plasma samples from 51 CRC patients and controls were tested for miR-182 expression. Plasma miR-182 concentrations were significantly higher in CRC patients than in healthy controls or patients with colon polyps at endoscopy. Moreover, miR-182 plasma levels were significantly reduced in post-operative samples after radical hepatic metastasectomy compared to preoperative samples. Our results strengthen the hypothesis of a central role of miR-182 dysregulation in colon mucosa transformation, demonstrate the concomitant progressive down-regulation of ENTPD5 levels during colon carcinogenesis, and indicate the potential of circulating miR 182 as blood based biomarker for screening and monitoring CRC during the follow up. PMID- 25115395 TI - Aurora kinase a suppresses metabolic stress-induced autophagic cell death by activating mTOR signaling in breast cancer cells. AB - Aberrant Aur-A signaling is associated with tumor malignant behaviors. However, its involvement in tumor metabolic stress is not fully elucidated. In the present study, prolonged nutrient deprivation was conducted into breast cancer cells to mimic metabolic stress in tumors. In these cells, autophagy was induced, leading to caspase-independent cell death, which was blocked by either targeted knockdown of autophagic gene ATG5 or autophagy inhibitor 3-Methyladenine (3-MA). Aur-A overexpression mediated resistance to autophagic cell death and promoted breast cancer cells survival when exposed to metabolic stress. Moreover, we provided evidence that Aur-A suppressed autophagy in a kinase-dependent manner. Furthermore, we revealed that Aur-A overexpression enhanced the mammalian target of rapamycin (mTOR) activity under metabolic stress by inhibiting glycogen synthase kinase 3beta (GSK3beta). Inhibition of mTOR activity by rapamycin sensitized Aur-A-overexpressed breast cancer cells to metabolic stress-induced cell death. Consistently, we presented an inverse correlation between Aur-A expression (high) and autophagic levels (low) in clinical breast cancer samples. In conclusion, our data provided a novel insight into the cyto-protective role of Aur-A against metabolic stress by suppressing autophagic cell death, which might help to develop alternative cell death avenues for breast cancer therapy. PMID- 25115396 TI - The microRNA-23b/27b/24-1 cluster is a disease progression marker and tumor suppressor in prostate cancer. AB - Our recent study of microRNA (miRNA) expression signatures in prostate cancer (PCa) has revealed that all members of the miR-23b/27b/24-1 cluster are significantly downregulated in PCa tissues. The aim of this study was to investigate the effectiveness of these clustered miRNAs as a disease progression marker and to determine the functional significance of these clustered miRNAs in PCa. Expression of the miR-23b/27b/24-1 cluster was significantly reduced in PCa tissues. Kaplan-Meier survival curves showed that low expression of miR-27b predicted a short duration of progression to castration-resistant PCa. Gain-of function studies using mature miR-23b, miR-27b,and miR-24-1 significantly inhibited cell proliferation, migration and invasion in PCa cells (PC3 and DU145). To identify the molecular targets of these miRNAs, we carried out gene expression and in silico database analyses. GOLM1 was directly regulated by miR 27b in PCa cells. Elucidation of the molecular targets and pathways regulated by the tumor-suppressive microRNAs should shed light on the oncogenic and metastatic processes in PCa. PMID- 25115393 TI - The miR-124-prolyl hydroxylase P4HA1-MMP1 axis plays a critical role in prostate cancer progression. AB - Collagen prolyl hydroxylases (C-P4HAs) are a family of enzymes involved in collagen biogenesis. One of the isoforms of P4HA, Prolyl 4-hydroxylase, alpha polypeptide I (P4HA1), catalyzes the formation of 4-hydroxyproline that is essential for the proper three-dimensional folding of newly synthesized procollagen chains. Here, we show the overexpression of P4HA1 in aggressive prostate cancer. Immunohistochemical analysis using tissue microarray demonstrated that P4HA1 expression was correlated with prostate cancer progression. Using in vitro studies, we showed that P4HA1 plays a critical role in prostate cancer cell growth and tumor progression. Expression profiling studies using P4HA1 modulated prostate cells suggested regulation of Matrix metalloproteases 1. The invasive properties of P4HA1 overexpressing cells were reversed by blocking MMP1. Our studies indicate P4HA1 copy number gain in a subset of metastatic prostate tumors and its expression is also regulated by microRNA-124. MiR-124 in turn is negatively regulated by transcriptional repressors EZH2 and CtBP1, both of which are overexpressed in aggressive prostate cancer. Chick chorioallantoic membrane (CAM) assay and mice xenograft investigations show that P4HA1 is required for tumor growth and metastasis in vivo. Our observations suggest that P4HA1 plays a critical role in prostate cancer progression and could serve as a viable therapeutic target. PMID- 25115397 TI - EZH2 dependent H3K27me3 is involved in epigenetic silencing of ID4 in prostate cancer. AB - Inhibitor of DNA binding/differentiation protein 4 (ID4) is dominant negative helix loop helix transcriptional regulator is epigenetically silenced due to promoter hyper-methylation in many cancers including prostate. However, the underlying mechanism involved in epigenetic silencing of ID4 is not known. Here, we demonstrate that ID4 promoter methylation is initiated by EZH2 dependent tri methylation of histone 3 at lysine 27 (H3K27me3). ID4 expressing (LNCaP) and non expressing (DU145 and C81) prostate cancer cell lines were used to investigate EZH2, H3K27me3 and DNMT1 enrichment on ID4 promoter by Chromatin immuno precipitation (ChIP). Enrichment of EZH2, H3K27Me3 and DNMT1 in DU145 and C81 cell lines compared to ID4 expressing LNCaP cell line. Knockdown of EZH2 in DU145 cell line led to re-expression of ID4 and decrease in enrichment of EZH2, H3K27Me3 and DNMT1 demonstrating that ID4 is regulated in an EZH2 dependent manner. ChIP data on prostate cancer tissue specimens and cell lines suggested EZH2 occupancy and H3K27Me3 marks on the ID4 promoter. Collectively, our data indicate a PRC2 dependent mechanism in ID4 promoter silencing in prostate cancer through recruitment of EZH2 and a corresponding increase in H3K27Me3. Increased EZH2 but decreased ID4 expression in prostate cancer strongly supports this model. PMID- 25115398 TI - Fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6 bisphosphatase 4 (PFKFB4) is required for the glycolytic response to hypoxia and tumor growth. AB - Fructose-2,6-bisphosphate (F2,6BP) is a shunt product of glycolysis that allosterically activates 6-phosphofructo-1-kinase (PFK-1) resulting in increased glucose uptake and glycolytic flux to lactate. The F2,6BP concentration is dictated by four bifunctional 6-phosphofructo-2-kinase/fructose-2,6 bisphosphatases (PFKFB1-4) with distinct kinase:phosphatase activities. PFKFB4 is over-expressed in human cancers, induced by hypoxia and required for survival and growth of several cancer cell lines. Although PFKFB4 appears to be a rational target for anti-neoplastic drug development, it is not clear whether its kinase or phosphatase activity is required for cancer cell survival. In this study, we demonstrate that recombinant human PFKFB4 kinase activity is 4.3-fold greater than its phosphatase activity, siRNA and genomic deletion of PFKFB4 decrease F2,6BP, PFKFB4 over-expression increases F2,6BP and selective PFKFB4 inhibition in vivo markedly reduces F2,6BP, glucose uptake and ATP. Last, we find that PFKFB4 is required for cancer cell survival during the metabolic response to hypoxia, presumably to enable glycolytic production of ATP when the electron transport chain is not fully operational. Taken together, our data indicate that the PFKFB4 expressed in multiple transformed cells and tumors functions to synthesize F2,6BP. We predict that pharmacological disruption of the PFKFB4 kinase domain may have clinical utility for the treatment of human cancers. PMID- 25115399 TI - Nuclear and cytoplasmic p53 suppress cell invasion by inhibiting respiratory complex-I activity via Bcl-2 family proteins. AB - Although the p53 tumor suppressor/transcription factor often accumulates in the cytoplasm of healthy cells, limited information is available on the cytoplasmic function of p53. Here, we show that cytoplasmic p53 suppresses cell invasion by reducing mitochondrial reactive oxygen species (ROS) levels. Analysis revealed that this function is mediated by Bcl-2 family proteins: Cytoplasmic p53 binds Bcl-w, liberating Bax, which then binds ND5, a subunit of respiratory complex-I, thereby suppressing complex-I activity and thus ROS production. The G13289A mutation of ND5, identified in cancer patients, prevents Bax/ND5 interactions and promotes ROS production and cell invasion. We also showed that Bcl-XL and Bak can substitute for Bcl-w and Bax, respectively, regulating complex-I activity and supporting the cytoplasmic function of p53; nuclear p53 also suppresses complex-I activity by inducing Bax expression. Studies in animal models support the notion that p53 and Bcl-2 family proteins exhibit these functions in vivo. This study demonstrates a link between p53 and Bcl-2 proteins as regulators of ROS production and cellular invasiveness, and reveals complex-I, especially ND5, as their functional target. PMID- 25115401 TI - Concerted action of target-site mutations and high EPSPS activity in glyphosate resistant junglerice (Echinochloa colona) from California. AB - BACKGROUND: Echinochloa colona is an annual weed affecting field crops and orchards in California. An E. colona population carrying a mutation in the EPSPS gene endowing resistance to glyphosate, the most widely used non-selective herbicide, was recently identified in the Northern Sacramento Valley of California. Plants from this population, from a suspected glyphosate-resistant (GR) population, and from one susceptible (S) population collected in the Northern Sacramento Valley of California, were used to generate three GR and one S selfed lines to study possible mechanisms involved in glyphosate resistance. RESULTS: Based on the amount of glyphosate required to kill 50% of the plants (LD50 ), GR lines were 4-9-fold more resistant than S plants and accumulated less shikimate after glyphosate treatment. GR and S lines did not differ in glyphosate absorption, translocation or metabolism. A different target-site mutation was found in each of two of the GR lines corresponding to Pro106Thr and Pro106Ser substitutions; the mutations were found in different homoeologous EPSPS genes. No mutation was found in the third GR line, which exhibited 1.4-fold higher basal EPSPS activity and a fivefold greater LD50 than S plants. Quantitative RT-PCR revealed that GR lines had similar or lower EPSPS expression than S plants. CONCLUSION: It is demonstrated that individuals with different glyphosate resistance mechanisms can coexist in the same population, individuals from different populations may carry different resistance mechanisms and different mechanisms can act in concert within single E. colona plants. However, other plant factors or resistance mechanisms appear to modulate plant expression of EPSPS sensitivity to glyphosate. PMID- 25115400 TI - Beclin-1-independent autophagy positively regulates internal ribosomal entry site dependent translation of hypoxia-inducible factor 1alpha under nutrient deprivation. AB - Hypoxia has been shown to induce hypoxia-inducible factor-1alpha (HIF-1alpha) expression to support many cellular changes required for tumor growth and metastasis. In addition to hypoxia, nutrient deprivation is another stress condition widely existing in solid tumors due to the poor blood supply. Our data showed that nutrient deprivation induces a significant HIF-1alpha protein expression and potentiates the HIF-1alpha responses of hypoxia and CoCl2. This effect is not because of enhancement of HIF-1alpha stability or transcription. Rather we found it is through the cap-independent but internal ribosome entry site (IRES)-dependent translation. Notably inhibition of autophagy by si-ATG5, 3 methyladenine and chloroquine, but not si-Beclin-1, significantly reverses nutrient deprivation-induced HIF-1alpha responses. Furthermore, it is interesting to note the contribution of IRES activation for hypoxia-induced HIF-1alpha expression, however, different from nutrient starvation, si-Beclin 1 but not si ATG5 can inhibit hypoxia-induced HIF-1alpha IRES activation and protein expression. Taken together, we for the first time highlight a link from alternative autophagy to cap-independent protein translation of HIF-1alpha under two unique stress conditions. We demonstrate Beclin 1-independent autophagy is involved to positively regulate nutrient deprivation induced-HIF-1alpha IRES activity and protein expression, while ATG5-independent autophagy is involved in the HIF-1 IRES activation caused by hypoxia. PMID- 25115404 TI - Annular lupus erythematosus profundus. PMID- 25115402 TI - MicroRNAs differentially regulated in cardiac and skeletal muscle in health and disease: potential drug targets? AB - The identification of non-coding RNA species, previously thought of as 'junk' DNA, adds a new dimension of complexity to the regulation of DNA, RNA and protein. MicroRNAs are short non-coding RNA species that control gene expression, are dysregulated in settings of cardiac and skeletal muscle disease and have emerged as promising therapeutic targets. MicroRNAs specifically enriched in cardiac and skeletal muscle are called myomiRs and play an important role in cardiac pathology and skeletal muscle biology. Moreover, microRNA profiles are altered in response to exercise and disease; thus, their potential as therapeutic drug targets is being widely explored. In the cardiovascular field, therapeutic inhibition of microRNAs has been shown to be effective in improving cardiac outcome in preclinical cardiac disease models. MicroRNAs that promote skeletal muscle regeneration are attractive therapeutic targets in muscle wasting conditions where regenerative capacity is compromised. PMID- 25115403 TI - Integrating team resource management program into staff training improves staff's perception and patient safety in organ procurement and transplantation: the experience in a university-affiliated medical center in Taiwan. AB - BACKGROUND: The process involved in organ procurement and transplantation is very complex that requires multidisciplinary coordination and teamwork. To prevent error during the processes, teamwork education and training might play an important role. We wished to evaluate the efficacy of implementing a Team Resource Management (TRM) program on patient safety and the behaviors of the team members involving in the process. METHODS: We implemented a TRM training program for the organ procurement and transplantation team members of the National Taiwan University Hospital (NTUH), a teaching medical center in Taiwan. This 15-month intervention included TRM education and training courses for the healthcare workers, focused group skill training for the procurement and transplantation team members, video demonstration and training, and case reviews with feedbacks. Teamwork culture was evaluated and all procurement and transplantation cases were reviewed to evaluate the application of TRM skills during the actual processes. RESULTS: During the intervention period, a total of 34 staff members participated the program, and 67 cases of transplantations were performed. Teamwork framework concept was the most prominent dimension that showed improvement from the participants for training. The team members showed a variety of teamwork behaviors during the process of procurement and transplantation during the intervention period. Of note, there were two potential donors with a positive HIV result, for which the procurement processed was timely and successfully terminated by the team. None of the recipients was transplanted with an infected organ. No error in communication or patient identification was noted during review of the case records. CONCLUSION: Implementation of a Team Resource Management program improves the teamwork culture as well as patient safety in organ procurement and transplantation. PMID- 25115405 TI - Quantitative analysis of intracellular communication and signaling errors in signaling networks. AB - BACKGROUND: Intracellular signaling networks transmit signals from the cell membrane to the nucleus, via biochemical interactions. The goal is to regulate some target molecules, to properly control the cell function. Regulation of the target molecules occurs through the communication of several intermediate molecules that convey specific signals originated from the cell membrane to the specific target outputs. RESULTS: In this study we propose to model intracellular signaling network as communication channels. We define the fundamental concepts of transmission error and signaling capacity for intracellular signaling networks, and devise proper methods for computing these parameters. The developed systematic methodology quantitatively shows how the signals that ligands provide upon binding can be lost in a pathological signaling network, due to the presence of some dysfunctional molecules. We show the lost signals result in message transmission error, i.e., incorrect regulation of target proteins at the network output. Furthermore, we show how dysfunctional molecules affect the signaling capacity of signaling networks and how the contributions of signaling molecules to the signaling capacity and signaling errors can be computed. The proposed approach can quantify the role of dysfunctional signaling molecules in the development of the pathology. We present experimental data on caspese3 and T cell signaling networks to demonstrate the biological relevance of the developed method and its predictions. CONCLUSIONS: This study demonstrates how signal transmission and distortion in pathological signaling networks can be modeled and studied using the proposed methodology. The new methodology determines how much the functionality of molecules in a network can affect the signal transmission and regulation of the end molecules such as transcription factors. This can lead to the identification of novel critical molecules in signal transduction networks. Dysfunction of these critical molecules is likely to be associated with some complex human disorders. Such critical molecules have the potential to serve as proper targets for drug discovery. PMID- 25115406 TI - A predisposition for allergies predicts subsequent hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder: a nationwide longitudinal study. AB - BACKGROUND: Previous studies have shown that both severe mental disorders (schizophrenia and bipolar disorder) and atopic diseases were associated with an increased risk of metabolic syndrome. However, the role of atopy/the predisposition for allergies in the development of metabolic syndrome is still unknown among those with severe mental disorders. METHODS: Using the Taiwan National Health Insurance Research Database, 5826 patients with schizophrenia or bipolar disorder (1908 with a predisposition for allergies and 3918 without) were enrolled between 1998 and 2008. Those who developed hypertension, dyslipidemia, and/or diabetes mellitus were identified during the follow-up to the end of 2011. RESULTS: A predisposition for allergies increased the risk of developing hypertension (HR: 1.67), dyslipidemia (HR: 1.82), and diabetes mellitus (HR: 1.37) in later life among those with severe mental disorders. A dose-dependent relationship was noted between having more atopic comorbidities and a greater likelihood of hypertension (1 atopic disease: HR: 1.60; ? 2 atopic comorbidities: HR: 1.87), dyslipidemia (HR: 1.73; HR: 2.12), and diabetes mellitus (HR: 1.26; HR: 1.69). CONCLUSION: A predisposition for allergies was an independent risk factor for hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder. Further studies would be required to elucidate the underlying pathophysiology among atopy, schizophrenia, bipolar disorder, and metabolic syndrome. PMID- 25115407 TI - Increased visual gamma power in schizoaffective bipolar disorder. AB - BACKGROUND: Electroencephalography and magnetoencephalography (MEG) studies have identified alterations in gamma-band (30-80 Hz) cortical activity in schizophrenia and mood disorders, consistent with neural models of disturbed glutamate (and GABA) neuron influence over cortical pyramidal cells. Genetic evidence suggests specific deficits in GABA-A receptor function in schizoaffective bipolar disorder (SABP), a clinical syndrome with features of both bipolar disorder and schizophrenia. This study investigated gamma oscillations in this under-researched disorder. METHOD: MEG was used to measure induced gamma and evoked responses to a visual grating stimulus, known to be a potent inducer of primary visual gamma oscillations, in 15 individuals with remitted SABP, defined using Research Diagnostic Criteria, and 22 age- and sex matched healthy controls. RESULTS: Individuals with SABP demonstrated increased sustained visual cortical power in the gamma band (t 35 = -2.56, p = 0.015) compared to controls. There were no group differences in baseline gamma power, transient or sustained gamma frequency, alpha band responses or pattern onset visual-evoked responses. CONCLUSIONS: Gamma power is increased in remitted SABP, which reflects an abnormality in the cortical inhibitory-excitatory balance. Although an interaction between gamma power and medication can not be ruled out, there were no group differences in evoked responses or baseline measures. Further work is needed in other clinical populations and at-risk relatives. Pharmaco magnetoencephalography studies will help to elucidate the specific GABA and glutamate pathways affected. PMID- 25115408 TI - Pyonephrosis Caused by Salmonella Typhi: A Case Report. AB - INTRODUCTION: Salmonella is a rare cause of urinary tract infections. We report here a unique case of pyonephrosis due to Salmonella Typhi (S. Typhi) complication, a stone-related obstructive pyelonephritis. CASE REPORT: A 47-year old man, without any history of typhoid fever or gastrointestinal symptoms, presented with a pyonephrosis and life-threatening bacteremia following an acute obstructive right pyelonephritis caused by S. Typhi. The patient was treated by urinary drainage (ureteral stent), antibiotics, and delayed right nephrectomy. We postulated that urolithiasis could explain asymptomatic chronic urinary carriage of S. Typhi. CONCLUSION: S. Typhi is one possible cause of life-threatening urinary tract infection, especially in the context of urolithiasis. PMID- 25115409 TI - Ethylene transposition: ruthenium hydride catalyzed intramolecular trans silylvinylation of internal alkynes. AB - A highly selective intramolecular trans-silylvinylation of internal alkynes catalyzed by RuHCl(CO)(SIMes)(PPh3) has been accomplished. The use of methyl vinyl ketone as an additive increased the efficiency of this transformation. This process was used to successfully form five-, six-, and seven-membered oxasilacycles by a formal anti-exo-dig cyclization. PMID- 25115412 TI - The FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC) Initiative in Maternal and Newborn Health. AB - The FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC) Initiative in Maternal and Newborn Health developed the organizational capacity of national professional organizations of obstetrics and gynecology in eight African and Asian countries. The initiative was funded by a grant from the Bill and Melinda Gates Foundation and had three key objectives. These goals were to support the eight FIGO member associations to strengthen their capacity to work effectively; to influence national policies on maternal and newborn health; and to work toward improving clinical practice in this area. The current supplement presents evidence that the focus and effectiveness of a national obstetric and gynecologic association-as well as its influence on major public health issues (such as United Nations Millennium Development Goals 4 and 5)-can be substantially broadened and enhanced by the provision of external support. PMID- 25115411 TI - Associated morbidity of pediatric ptosis - a large, community based case-control study. AB - PURPOSE: To report the incidence, demographics, and associations of various conditions among patients with pediatric ptosis. METHODS: A retrospective, observational case-control study of patients (birth-18 years; n = 2,408) diagnosed with pediatric ptosis in 1/2003-12/2012. Age- and gender-matched control patients (n = 9,632) were randomly selected from the district members. Medical and socio-demographic information were extracted from electronic medical records. RESULTS: The average age of diagnosis was 5.6 years, and 1,325 (54%) were male, with an incidence of 19.9/100,000. Systemic conditions significantly associated with pediatric ptosis include myasthenia gravis, congenital anomalies, deafness, mental retardation, muscular dystrophy, neurological diseases, epilepsy, schizophrenia, and malignancy. Ophthalmic conditions associated with pediatric ptosis include exotropia, progressive external ophthalmoplegia, hypotropia, esotropia, hyperopia, vertical heterophoria, intermitent esotropia, astigmatism, retinopathy, internuclear ophthalmoplegia, and myopia. Symptoms of diplopia, blurred vision, and aniseikonia were significantly more common. CONCLUSION: Pediatric ptosis is associated with various systemic and ophthalmic conditions, and many are diagnosed after the age of 5 years. Clinicians should maintain a high degree of suspicion and thoroughly evaluate all patients with pediatric ptosis to properly assess underlying systemic associations. A better understanding of the patho-physiological association between these factors and pediatric ptosis may help its prevention and treatment. PMID- 25115413 TI - Revising the high-density lipoprotein targeting strategies - insights from human and preclinical studies. AB - In recent years, the high-density lipoprotein (HDL) hypothesis has been challenged. Several completed randomized clinical trials continue to fall short in demonstrating HDL, or at least HDL-cholesterol (HDL-C) levels, as being a consistent target in the prevention of cardiovascular diseases. However, population studies and findings in lipid modifying trials continue to strongly support HDL-C as a superb risk predictor. It is increasingly evident that the complexity of HDL metabolism confounds the use of HDL-C concentration as a unified target. However, important insights continue to emerge from the post hoc analyses of recently completed (i) fibrate-based FIELD and ACCORD trials, including the unexpected beneficial effect of fibrates in microvascular diseases, (ii) the niacin-based AIM-HIGH and HPS2-THRIVE studies, (iii) recombinant HDL based as well as (iv) the completed CETP inhibitor-based trials. These together with on-going mechanistic studies on novel pathways, which include the unique roles of microRNAs, post-translational remodeling of HDL and novel pathways related to HDL modulators will provide valuable insights to guide how best to refocus and redesign the conceptual framework for selecting HDL-based targets. PMID- 25115414 TI - Proton magnetic resonance spectroscopy assessment of fetal brain metabolism in late-onset 'small for gestational age' versus 'intrauterine growth restriction' fetuses. AB - OBJECTIVES: We used magnetic resonance spectroscopy (MRS) to evaluate brain metabolic differences in small fetuses near term as compared to appropriate for gestational age (AGA) fetuses. STUDY DESIGN: 71 term small fetuses (estimated fetal weight <10th centile for gestational age with normal umbilical artery Doppler sonography) were subclassified as late intrauterine growth restriction (IUGR) (n = 50) or small for gestational age (SGA) (n = 21), and compared with 65 AGA fetuses. IUGR was defined by either abnormal middle cerebral artery, abnormal uterine artery Doppler sonography or estimated fetal weight <3rd centile. All participants underwent brain magnetic resonance imaging at 37 weeks of gestation, and single-voxel magnetic resonance spectra were obtained from the frontal lobe on a 3-tesla scanner. N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr) and Cho/Cr ratios were calculated and compared between cases and controls. The association of the metabolic ratios with the study groups was tested. RESULTS: After MRS processing and applying quality control criteria, 31 spectra from late onset IUGR, 11 from SGA and 30 from AGA fetuses were selected for further analysis. Both SGA and late-onset IUGR fetuses showed significantly reduced NAA/Cho levels when compared to AGA fetuses. This decrease followed a linear trend across the three clinical groups that were considered. CONCLUSIONS: Both SGA and late-onset IUGR fetuses showed differences in MRS brain metabolic ratios. The findings suggest that despite near-normal perinatal outcomes, SGA fetuses are not constitutionally small and may represent a form of growth disorder that needs to be clarified. PMID- 25115415 TI - Memories of Holocaust-related traumatic experiences, sense of coherence, and survivors' subjective well-being in late life: some puzzling findings. AB - BACKGROUND AND OBJECTIVES: This study explores the nexus of relationships between memories of Holocaust-related early traumatic events, survivors' sense of coherence (SOC), and subjective well-being (SWB) in late life. DESIGN: The basic design of this study, based 106 survivors (54% female), was cross-sectional. METHODS: Participants underwent an extensive in-depth clinical interview relating to their Holocaust experiences and responded to measures of SOC and SWB. RESULTS: These data provided no evidence for the moderating or "buffering" effect of SOC but showed support for indirect effects of SOC in the relationship between memory traces of specific traumatic experiences and adaptive outcomes. CONCLUSIONS: The results of the present study provide support for Antonovsky's salutogenic perspective. It is highly plausible that survivors who underwent severe experiences during the Holocaust period were forced to call upon all their inner strengths and coping resources,and that their success in doing so and also surviving this horrendous period, might have contributed to the development of a stronger sense of meaning and coherence, which, in turn lead to a better sense of mental health as they approach the final season of their lives. PMID- 25115410 TI - Temporal trends from 1986 to 2008 in overall survival of small cell lung cancer patients. AB - OBJECTIVES: An assessment of temporal trends in patient survival is important to determine the progress toward patient outcomes and to reveal where advancements must be made. This study assessed temporal changes spanning 22years in demographics, clinical characteristics, and overall survival of small cell lung cancer (SCLC) patients. MATERIALS AND METHODS: This analysis included 1032 SCLC patients spanning two time-periods from the H. Lee Moffitt Cancer Center and Research Institute: 1986-1999 (N=410) and 2000-2008 (N=622). Kaplan-Meier survival curves and log-rank statistics were used to assess survival rates across the two time-periods and multivariable Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The overall 5-year survival rate significantly increased from 8.3% for the 1986-1999 time-period to 11.0% (P<0.001) for the 2000-2008 time-period, and the median survival time increased from 11.3months (95% CI 10.5-12.7) to 15.2months (95% CI 13.6-16.6). We also observed significant increases in stage-specific median survival times and survival rates across the two time-periods. A multivariable Cox proportional hazards model for the entire cohort revealed significant increased risk of death for patients diagnosed in 1986-1999 (HR=1.29; 95% CI 1.11 1.49), patients diagnosed between 60 and 69years of age (HR=1.33; 95% CI 1.04 1.49) and over 70years of age (HR=1.63; 95% CI 1.26-2.11), men (HR=1.33; 95% CI 1.16-1.53), patients with no first course treatment (HR=2.17; 95% CI 1.57-3.00) and extensive stage SCLC (HR=2.79; 95% CI 2.35-3.30). CONCLUSION: This analysis demonstrated significant improvements in overall and stage-specific median survival times and survival rates of SCLC patients treated at the Moffitt Cancer Center from 1986 to 2008. PMID- 25115416 TI - Effect of hyoscine N-butylbromide on adenoma detection rate: meta-analysis of randomized clinical trials. AB - BACKGROUND AND AIM: Anti-spasmodic drugs may facilitate mucosal inspection during colonoscopy. The impact of hyoscine N-butylbromide (HBB) on polyp detection rate (PDR) and adenoma detection rate (ADR) is unclear. METHODS: We conducted a reproducible literature search of multiple databases. Two reviewers independently compared manuscripts for PDR, ADR, advanced adenoma detection rate (AADR), and rates of complications. Pooling was conducted by fixed-effects and random-effects models. Relative risk (RR) estimates were calculated (95% confidence interval). I(2) index assessed heterogeneity. RESULTS: Patient demographics were comparable. The pooled analysis showed a trend toward improving PDR and ADR among the HBB group compared with the placebo group but failed to reach statistical significance, (46% vs 43%, RR = 1.08 [0.94, 1.25], P = 0.27), (31% vs 28%, RR = 1.12 [0.97, 1.29], P = 0.11) respectively. CONCLUSION: HBB during colonoscopy may provide marginal improvements in ADR and PDR. However, heterogeneity in the available data precludes firm conclusions at this time. PMID- 25115417 TI - Lessons learned from the study of 10,000 patients with soft tissue sarcoma. AB - BACKGROUND AND OBJECTIVE: The management of rare tumors is difficult because of limited information on natural history. Our objective was to describe a long-term comprehensive prospective database with the assumption that with careful attention to patient, predisposing tumor and treatment variables, valuable knowledge could be obtained that could guide management. METHODS: In July of 1982, we began a prospective database of all adult patients admitted to our institution for a surgical procedure for soft tissue sarcoma. Patients were included if they had primary, locally recurrent or metastatic disease undergoing a surgical procedure. RESULTS: Over 3 decades, we entered 10,000 patients into our prospective soft tissue sarcoma database. Data were entered on a weekly or biweekly schedule with full participation of a multidisciplinary team and a dedicated sarcoma pathologist. Extensive information is available from this database. In this article, we describe distribution by site, histopathology, sex, size, and grade. We utilize this information along with outcome data for local recurrence, distant recurrence, disease specific, and overall survival. The value of molecular diagnosis is illustrated. CONCLUSIONS: Continuous prospective long term databases are important to obtain knowledge particularly for rare tumors. Such data can be a rich resource for the development of prognostic indicators including nomograms and can be analyzed by Bayesian Belief Networks. These long term data linked to collection of tumor and germ-line tissue at the time of an initial procedure will remain a resource for future decades. PMID- 25115418 TI - Risk of readmission and emergency surgery following nonoperative management of colonic diverticulitis: a population-based analysis. AB - OBJECTIVE: To characterize the clinical course of patients with diverticulitis after nonoperative management and determine factors associated with readmission and subsequent emergency surgery. BACKGROUND: Clinical course of this disease remains poorly understood; indications for elective colectomy are unclear. METHODS: This was a retrospective cohort study of patients managed nonoperatively after a first episode of diverticulitis in Ontario, Canada (2002-2012). Time-to event analysis and Fine and Gray multivariable regression were used to characterize the risks of readmission and emergency surgery for diverticulitis, accounting for death and elective colectomy as competing events. RESULTS: A total of 14,124 patients were followed for a median of 3.9 years (maximum 10, interquartile range: 1.7-6.4). Five-year cumulative incidence was 9.0% for readmission, 1.9% for emergency surgery, and 14.1% for all-cause mortality. Patients younger than 50 years had higher incidence of readmission than patients aged 50 years and older (10.5% vs 8.4%; P < 0.001) but not emergency surgery (1.8% vs 2.0%; P = 0.52). Patients with complicated disease (abscess, perforation) were at increased risk of readmission than those with uncomplicated disease (12.0% vs 8.2%; P < 0.001), as well as increased risk of emergency surgery (4.3% vs 1.4%, P < 0.001). In multivariable regression, complicated disease and number of prior admissions were associated with increased risk of emergency surgery, yet age less than 50 years was not. Risks associated with complicated disease were nonproportional over time, being highest immediately after discharge and decreasing thereafter. CONCLUSIONS: Absolute risks of readmission and emergency surgery are low after nonoperative management of diverticulitis, providing evidence for the practice of deferring colectomy for patients without persistent symptoms or multiple recurrences. PMID- 25115420 TI - The HYSLAR trial: a prospective randomized controlled trial of the use of a restrictive fluid regimen with 3% hypertonic saline versus lactated Ringers in patients undergoing pancreaticoduodenectomy. AB - OBJECTIVE: This study was designed to determine whether the volume and type of fluid administered for pancreaticoduodenectomy impacts postoperative outcomes. BACKGROUND: Three percent hypertonic saline (HYS) has been suggested as a means of reducing the volume of fluid required to sustain tissue perfusion in the perioperative period. METHODS: Between May 2011 and November 2013, patients undergoing pancreaticoduodenectomy were enrolled in an institutional review board approved, single-center, prospective, parallel, randomized controlled trial (NCT 01428050), comparing lactated Ringers (LAR) (15 mL/kg/hr LAR intraoperation, 2 mL/kg/hr LAR postoperation) with HYS (9 mL/kg/hr LAR and 1 mL/kg/hr HYS intraoperation, 1 mL/kg/hr HYS postoperation). RESULTS: A total of 264 patients were randomized. Demographic variables between groups were similar. The HYS patients had a significantly reduced net fluid balance (65 vs 91 mL/kg, P = 0.02). The overall complication rate was reduced in the HYS group (43% vs 54%), with a relative risk of 0.79 [95% confidence interval (CI), 0.62-1.02; P = 0.073], factoring stratification for pancreas texture. After adjustment for age and weight, the relative risk was 0.75 [95% CI (0.58-0.96); P = 0.023]. The total number of complications was significantly reduced in the HYS group (93 vs 123), with an incidence rate ratio of 0.74 [95% CI (0.56-0.97); P = 0.027]. After adjustment for age and weight, the incidence rate ratio was 0.69 [95% CI (0.52 0.90); P = 0.0068]. Reoperations, length of stay, readmissions, and 90-day mortality were similar between groups. CONCLUSIONS: A moderately restrictive fluid regimen with HYS resulted in a statistically significant 25% reduction in complications when adjusted for age, weight, and pancreatic texture. PMID- 25115419 TI - The enteric nervous system neuropeptide, bombesin, reverses innate immune impairments during parenteral nutrition. AB - BACKGROUND: Lack of enteral stimulation during parenteral nutrition (PN) impairs mucosal immunity. Bombesin (BBS), a gastrin-releasing peptide analogue, reverses PN-induced defects in acquired immunity. Paneth cells produce antimicrobial peptides (AMPs) of innate immunity for release after cholinergic stimulation. OBJECTIVE: Determine if BBS restores AMPs and bactericidal function during PN. METHODS: Intravenously cannulated male ICR mice were randomized to Chow, PN, or PN+BBS (15 MUg 3 times daily, n = 7 per group) for 5 days. Ileum was analyzed for AMPs (Protein: sPLA2 by fluorescence, lysozyme and RegIII-gamma by western andcryptdin-4 by ELISA; mRNA: all by RT-PCR). Cholinergic stimulated (100 MUM bethanechol) ileal specimens assessed Pseudomonas bactericidal activity. Ileum (Chow: n = 7; PN: n = 9; PN+BBS: n = 8) was assessed for Escherichia coli invasion in ex-vivo culture. RESULTS: PN significantly decreased most AMPs versus Chow while BBS maintained Chow levels (sPLA2: Chow: 107 + 14*, PN: 44.6 + 7.2, PN+BBS: 78.7 + 13.4* Fl/min/MUL/total protein; Lysozyme: Chow: 63.9 + 11.9*, PN: 26.8 + 6.2; PN+BBS: 64.9 + 13.8* lysozyme/total protein; RegIII-gamma: Chow: 51.5 + 10.0*, PN: 20.4 + 4.3, PN+BBS: 31.0 + 8.4 RegIII-gamma/total protein; Cryptdin 4: Chow: 18.4 + 1.5*, PN: 12.7 + 1.6, PN+BBS: 26.1 + 2.4*? pg/mg [all *P < 0.05 vs PN and ?P < 0.05 vs Chow]). Functionally, BBS prevented PN loss of bactericidal activity after cholinergic stimulation (Chow: 25.3 + 3.6*, PN: 13.0 + 3.2; PN+BBS: 27.0 + 4.7* percent bacterial killing, *P < 0.05 vs PN). BBS reduced bacterial invasion in unstimulated tissue barely missing significance (P = 0.06). CONCLUSIONS: The enteric nervous system (ENS) controls AMP levels in Paneth cells during PN but mucosal protection by innate immunity requires both ENS and parasympathetic stimulation. PMID- 25115422 TI - Disease severity, not operative approach, drives organ space infection after pediatric appendectomy. AB - OBJECTIVE: This study examines patient and operative factors associated with organ space infection (OSI) in children after appendectomy, specifically focusing on the role of operative approach. BACKGROUND: Although controversy exists regarding the risk of increased postoperative intra-abdominal infections after laparoscopic appendectomy, this approach has been largely adopted in the treatment of pediatric acute appendicitis. METHODS: Children aged 2 to 18 years undergoing open or laparoscopic appendectomy for acute appendicitis were selected from the 2012 American College of Surgeons Pediatric National Surgical Quality Improvement Program database. Univariate analysis compared patient and operative characteristics with 30-day OSI and incisional complication rates. Factors with a P value of less than 0.1 and clinical importance were included in the multivariable logistic regression models. A P value less than 0.05 was considered significant. RESULTS: For 5097 children undergoing appendectomy, 4514 surgical procedures (88.6%) were performed laparoscopically. OSI occurred in 155 children (3%), with half of these infections developing postdischarge. Significant predictors for OSI included complicated appendicitis, preoperative sepsis, wound class III/IV, and longer operative time. Although 5.2% of patients undergoing open surgery developed OSI (odds ratio = 1.82; 95% confidence interval, 1.21 2.76; P = 0.004), operative approach was not associated with increased relative odds of OSI (odds ratio = 0.99; confidence interval, 0.64-1.55; P = 0.970) after adjustment for other risk factors. Overall, the model had excellent predictive ability (c-statistic = 0.837). CONCLUSIONS: This model suggests that disease severity, not operative approach, as previously suggested, drives OSI development in children. Although 88% of appendectomies in this population were performed laparoscopically, these findings support utilization of the surgeon's preferred surgical technique and may help guide postoperative counsel in high-risk children. PMID- 25115423 TI - Primary hyperparathyroidism with negative imaging: a significant clinical problem. AB - OBJECTIVE: To compare the outcomes for patients undergoing parathyroidectomy for primary hyperparathyroidism by imaging results. BACKGROUND: Preoperative imaging plays an increasingly important role in the evaluation of primary hyperparathyroidism, and surgical referral may be predicated upon successful imaging. METHODS: We performed a retrospective study of patients undergoing initial parathyroidectomy for primary hyperparathyroidism (2002-2014). Patients were classified as nonlocalized when preoperative imaging failed to identify affected gland(s) and localized if successful. Primary outcome was cure, defined as eucalcemia postoperatively. Intraoperative success, defined by intraoperative parathyroid hormone criteria, and complication rates were also analyzed. Localized and nonlocalized patients were matched (1:1) utilizing a propensity score. Logistic regression determined factors associated with localization in the matched cohort. RESULTS: Of 2185 patients, 38.3% (n = 836) were nonlocalized. Nonlocalized patients had smaller parathyroids by size (1.2 vs 1.6 cm, P < 0.001) and mass (250 vs 537 mg, P < 0.001), higher incidence of hyperplasia (12.8% vs 5.4%, P < 0.001) and lower incidence of single adenoma (73.6 vs 86.0%, P < 0.001) compared with localized patients. There was no difference in intraoperative success (93.9 vs 95.6%, P = 0.073) or cure rates (96.2% vs 97.7%, P = 0.291) between nonlocalized and localized groups. In a propensity-matched cohort of 452 patients, there was no significant difference in cure rates (97.8 vs 97.4%, P = 0.760) between nonlocalized patients and matched localized controls. CONCLUSIONS: Nonlocalization of abnormal glands preoperatively is not associated with a decreased surgical cure rate for primary hyperparathyroidism. Referral for surgical evaluation should be based on biochemical diagnosis rather than localization by imaging. PMID- 25115421 TI - Increased trauma center volume is associated with improved survival after severe injury: results of a Resuscitation Outcomes Consortium study. AB - OBJECTIVE: To investigate the relationship between trauma center volume and outcome. BACKGROUND: The Resuscitation Outcomes Consortium is a network of 11 centers and 60 hospitals conducting emergency care research. For many procedures, high-volume centers demonstrate superior outcomes versus low-volume centers. This remains controversial for trauma center outcomes. METHODS: This study was a secondary analysis of prospectively collected data from the Resuscitation Outcomes Consortium multicenter out-of-hospital Hypertonic Saline Trial in patients with Glasgow Coma Scale score of 8 or less (traumatic brain injury) or systolic blood pressure of 90 or less and pulse of 110 or more (shock). Regression analyses evaluated associations between trauma volume and the following outcomes: 24-hour mortality, 28-day mortality, ventilator-free days, Multiple Organ Dysfunction Scale incidence, worst Multiple Organ Dysfunction Scale score, and poor 6-month Glasgow Outcome Scale-Extended score. RESULTS: A total of 2070 patients were evaluated: 1251 in the traumatic brain injury cohort and 819 in the shock cohort. Overall, 24-hour and 28-day mortality was 16% and 25%, respectively. For every increase of 500 trauma center admissions, there was a 7% decreased odds of 24-hour and 28-day mortality for all patients. As trauma center volume increased, nonorgan dysfunction complications increased, ventilator free days increased, and worst Multiple Organ Dysfunction Scale score decreased. The associations with higher trauma center volume were similar for the traumatic brain injury cohort, including better neurologic outcomes at 6 months, but not for the shock cohort. CONCLUSIONS: Increased trauma center volume was associated with increased survival, more ventilator-free days, and less severe organ failure. Trauma system planning and implementation should avoid unnecessary duplication of services. PMID- 25115424 TI - Trainee participation is associated with adverse outcomes in emergency general surgery: an analysis of the National Surgical Quality Improvement Program database. AB - OBJECTIVE: To identify whether resident involvement affects clinically relevant outcomes in emergency general surgery. BACKGROUND: Previous research has demonstrated a significant impact of trainee participation on outcomes in a broad surgical patient population. METHODS: We identified 141,010 patients who underwent emergency general surgery procedures in the 2005-2010 Surgeons National Surgical Quality Improvement Program database. Because of the nonrandom assignment of complex cases to resident participation, patients were matched (1:1) on known risk factors [age, sex, inpatient status, preexisting comorbidities (obesity, diabetes, smoking, alcohol, steroid use, coronary artery disease, chronic renal failure, pulmonary disease)] and preoperatively calculated probability for morbidity and mortality. Clinically relevant outcomes were compared with a t or chi test. The impact of resident participation on outcomes was assessed with multivariable regression modeling, adjusting for risk factors and operative time. RESULTS: The most common procedures in the matched cohort (n = 83,790) were appendectomy (39.9%), exploratory laparotomy (8.8%), and adhesiolysis (6.6%). Trainee participation is independently associated with intra and postoperative events, wound, pulmonary, and venous thromboembolic complications, and urinary tract infections. CONCLUSIONS: Trainee participation is associated with adverse outcomes in emergency general surgery procedures. PMID- 25115426 TI - Does hospital accreditation impact bariatric surgery safety? AB - OBJECTIVE: To evaluate the impact of hospital accreditation upon bariatric surgery outcomes. BACKGROUND: Since 2004, the American College of Surgeons and the American Society of Metabolic and Bariatric Surgery have accredited bariatric hospitals. Few studies have evaluated the impact of hospital accreditation on all bariatric surgery outcomes. METHODS: Bariatric surgery hospitalizations were identified using International Classification of Diseases, Ninth Revision (ICD9) codes in the 2010 Nationwide Inpatient Sample (NIS). Hospital names and American Hospital Association (AHA) codes were used to identify accredited bariatric centers. Relevant ICD9 codes were used for identifying demographics, length of stay (LOS), total charges, mortality, complications, and failure to rescue (FTR) events. RESULTS: There were 117,478 weighted bariatric patient discharges corresponding to 235 unique hospitals in the 2010 NIS data set. A total of 72,615 (61.8%) weighted discharges, corresponding to 145 (61.7%) named or AHA identifiable hospitals were included. Among the 145 hospitals, 66 (45.5%) were unaccredited and 79 (54.5%) accredited. Compared with accredited centers, unaccredited centers had a higher mean LOS (2.25 vs 1.99 days, P < 0.0001), as well as total charges ($51,189 vs $42,212, P < 0.0001). Incidence of any complication was higher at unaccredited centers than at accredited centers (12.3% vs 11.3%, P = 0.001), as was mortality (0.13% vs 0.07%, P = 0.019) and FTR (0.97% vs 0.55%, P = 0.046). Multivariable logistic regression analysis identified unaccredited status as a positive predictor of incidence of complication [odds ratio (OR) = 1.08, P < 0.0001], as well as mortality (OR = 2.13, P = 0.013). CONCLUSIONS AND RELEVANCE: Hospital accreditation status is associated with safer outcomes, shorter LOS, and lower total charges after bariatric surgery. PMID- 25115425 TI - Value of intraoperative neck margin analysis during Whipple for pancreatic adenocarcinoma: a multicenter analysis of 1399 patients. AB - INTRODUCTION: During pancreaticoduodenectomy (PD) for ductal adenocarcinoma, a frozen section (FS) neck margin is typically assessed, and if positive, additional pancreas is removed to achieve an R0 margin. We analyzed the association of this practice with improved overall survival (OS). METHODS: Patients who underwent PD for pancreatic ductal adenocarcinoma from January 2000 to August 2012 at 8 academic centers were classified by neck margin status as negative (R0) or microscopically positive (R1) on the basis of FS and permanent section (PS). Impact on OS of converting an FS-R1-neck margin to a PS-R0-neck margin by additional resection was assessed. RESULTS: A total of 1399 patients had FS neck margins analyzed. Median OS was 19.7 months. On FS, 152 patients (10.9%) were R1, and an additional 51 patients (3.6%) had false-negative FS-R0 margins. PS-R0-neck was achieved in 1196 patients (85.5%), 131 patients (9.3%) remained PS-R1, and 72 patients (5.1%) were converted from FS-R1-to-PS-R0 by additional resection. Median OS for PS-R0-neck patients was 21.1 months versus 13.7 months for PS-R1-neck patients (P < 0.001) and 11.9 months for FS-R1-to-PS R0 patients (P < 0.001). Both FS-R1-to-PS-R0 and PS-R1-neck patients had larger tumors (P = 0.001), more perineural invasion (P = 0.02), and more node positivity (P = 0.08) than PS-R0-neck patients. On multivariate analysis controlling for adverse pathologic factors, FS-R1-to-PS-R0 conversion remained associated with significantly worse OS compared with PS-R0-neck patients (hazard ratio: 1.55; P = 0.009). CONCLUSIONS: For patients who undergo pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, additional resection to achieve a negative neck margin after positive frozen section is not associated with improved OS. PMID- 25115427 TI - Repair of extensive aortic aneurysms: a single-center experience using the elephant trunk technique over 20 years. AB - OBJECTIVES: We report the early and late outcomes after repair of extensive aortic aneurysms using the 2-stage elephant trunk (ET) technique. BACKGROUND: Management of aneurysm involving the entire aorta is a significant challenge. Given the anatomical complexity, the staged ET procedure was devised. A paucity of long-term data of outcomes of this approach exists. METHODS: A single-center retrospective analysis of a prospectively collected database of all patients undergoing repair for extensive aortic aneurysm was performed. RESULTS: Between 1991 and 2013, we repaired 3012 aneurysms of the ascending or thoracoabdominal aorta. Of these, we performed 503 operations in 348 patients using the ET technique. Mean age was 62.4 +/- 14.3 years, and 156/346 (45.1%) operations were in women; 288 patients underwent first-stage ET with 157 receiving a complete second-stage repair. Index repair early mortality was 29/317 (9.1%). Completion stage early mortality was 17/186 = 9.1%. Stroke after first-stage ET repair was 10/297 (3.4%) and immediate neurologic deficit after the second-stage ET repair was 6/206 (2.9%). In the 131 patients who did not receive a second-stage repair, 17.8% died in the interval between 31 and 45 days. CONCLUSIONS: Extensive aortic aneurysm is a complex problem, but it can be managed safely with a 2-stage open procedure. Those patients who could not complete the completion repair fared poorly. Better predictors for early outcome need to be determined. The use of ET technique remains a valuable approach for repair of extensive aortic aneurysm. PMID- 25115428 TI - Laser resurfacing and remodeling of hypertrophic burn scars: the results of a large, prospective, before-after cohort study, with long-term follow-up. AB - OBJECTIVES: Hypertrophic burn scars produce significant morbidity, including itching, pain, stiffness, and contracture, but best management practices remain unclear. We present the largest study to date that examines long-term impact of laser therapies, a potentially transformative technology, on scar remodeling. METHODS: We conducted a prospective, before-after cohort study in burn patients with hypertrophic scars. Pulsed-dye laser was used for pruritus and erythema; fractional CO2 laser was used for stiffness and abnormal texture. Outcomes included (1) Vancouver Scar Scale (VSS), which documents pigmentation, erythema, pliability, and height, and (2) University of North Carolina "4P" Scar Scale (UNC4P), which rates pain, pruritus, paresthesias, and pliability. RESULTS: A total of 147 burn patients (mean age, 26.9 years; total body surface area, 16.1%) received 415 laser sessions (2.8 sessions/patient), 16 months (median) after injury, including pulsed dye laser (n = 327) and CO2 (n = 139). Laser treatments produced rapid, significant, and lasting improvements in hypertrophic scar. Provider-rated VSS dropped from 10.43 [standard deviation (SD) 2.37] to 5.16 (SD 1.92), by the end of treatments, and subsequently decreased to 3.29 (SD 1.24), at a follow-up of 25 months. Patient-reported UNC4P fell from 5.40 (SD 2.54) to 2.05 (SD 1.67), after the first year, and further decreased to 1.74 (SD 1.72), by the end of the study period. CONCLUSIONS: For the first time, ever, in a large prospective study, laser therapies have been shown to dramatically improve both the signs and symptoms of hypertrophic burn scars, as measured by objective and subjective instruments. Laser treatment of burn scars represents a disruptive innovation that can yield results not previously possible and may displace traditional methods of operative intervention. PMID- 25115429 TI - Addressing the appropriateness of elective colon resection for diverticulitis: a report from the SCOAP CERTAIN collaborative. AB - OBJECTIVE: To assess the reported indications for elective colon resection for diverticulitis and concordance with professional guidelines. BACKGROUND: Despite modern professional guidelines recommending delay in elective colon resection beyond 2 episodes of uncomplicated diverticulitis, the incidence of elective colectomy has increased dramatically in the last 2 decades. Whether surgeons have changed their threshold for recommending a surgical intervention is unknown. In 2010, Washington State's Surgical Care and Outcomes Assessment Program initiated a benchmarking and education initiative related to the indications for colon resection. METHODS: Prospective cohort study evaluating indications from chronic complications (fistula, stricture, bleeding) or the number of previously treated diverticulitis episodes for patients undergoing elective colectomy at 1 of 49 participating hospitals (2010-2013). RESULTS: Among 2724 patients (58.7 +/- 13 years; 46% men), 29.4% had a chronic complication indication (15.6% fistula, 7.4% stricture, 3.0% bleeding, 5.8% other). For the 70.5% with an episode-based indication, 39.4% had 2 or fewer episodes, 56.5% had 3 to 10 episodes, and 4.1% had more than 10 episodes. Thirty-one percent of patients failed to meet indications for either a chronic complication or 3 or more episodes. Over the 4 years, the proportion of patients with an indication of 3 or more episodes increased from 36.6% to 52.7% (P < 0.001) whereas the proportion of those who failed to meet either clinical or episode-based indications decreased from 38.4% to 26.4% (P < 0.001). The annual rate of emergency resections did not increase significantly, varying from 5.6 to 5.9 per year (P = 0.81). CONCLUSIONS: Adherence to a guideline based on 3 or more episodes for elective colectomy increased concurrently with a benchmarking and peer-to-peer messaging initiative. Improving adherence to professional guidelines related to appropriate care is critical and can be facilitated by quality improvement collaboratives. PMID- 25115430 TI - Preoperative methylprednisolone enhances recovery after endovascular aortic repair: a randomized, double-blind, placebo-controlled clinical trial. AB - OBJECTIVE: To evaluate effects of preoperative high-dose glucocorticoid on the inflammatory response and recovery after endovascular aortic aneurysm repair (EVAR). BACKGROUND: The postimplantation syndrome after EVAR may delay recovery due to the release of proinflammatory mediators. Glucocorticoids may reduce postoperative inflammatory responses and enhance recovery, but with limited information on EVAR. METHODS: A single-center, randomized, double-blind, placebo controlled trial of 153 patients undergoing elective EVAR between November 2009 and January 2013. Patients received 30 mg/kg of methylprednisolone (MP) (n = 77) or placebo (n = 76) preoperatively. Primary outcome was a modified version of the systemic inflammatory response syndrome. Secondary outcome measures were the effect on inflammatory biomarkers, morbidity, and time to meet discharge criteria. RESULTS: Of 153 randomized patients, 150 (98%) were evaluated for the primary outcome. MP reduced systemic inflammatory response syndrome from 92% to 27% (P < 0.0001) (number needed to treat = 1.5), maximal plasma interleukin 6 from 186 pg/mL [interquartile range (IQR) = 113-261 pg/mL] to 20 pg/mL (IQR = 11 28 pg/mL) (P < 0.001) and fulfillment of discharge criteria was shorter [2 days (IQR = 2-4 days) vs 3 days (IQR = 3-4 days)] (P < 0.001). C-reactive protein, temperature, interleukin 8, and soluble tumor necrosis factor receptor were also reduced (P < 0.001) by MP. Myeloperoxidase, D-dimer, and matrix metalloproteinase 9 were not modified. No differences in 30-day medical (23% vs 36%) (P = 0.1) or surgical (20% vs 21%) morbidity were found in the active group versus the placebo group. CONCLUSIONS: Preoperative MP attenuates the inflammatory response with a faster recovery after EVAR for abdominal aortic aneurysms. Further safety and dose-response studies are required to allow recommendations for general practice. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00989729. PMID- 25115431 TI - Market competition influences renal transplantation risk and outcomes. AB - OBJECTIVE: To evaluate the impact of market competition on patient mortality and graft failure after kidney transplantation. BACKGROUND: Kidneys are initially allocated within 58 donation service areas (DSAs), which have varying numbers of transplant centers. Market competition is generally considered beneficial. METHODS: The Scientific Registry of Transplant Recipients database was queried and the Herfindahl-Hirschman index (HHI), a measure of market competition, was calculated for each DSA from 2003 to 2012. Receipt of low-quality kidneys (Kidney Donor Profile Index >= 85) was modeled with multivariable logistic regression, and Cox proportional hazards models were created for graft failure and patient mortality. RESULTS: A total of 127,355 adult renal transplants were performed. DSAs were categorized as 7 no (HHI = 1), 17 low (HHI = 0.52-0.97), 17 medium (HHI = 0.33-0.51), or 17 high (HHI = 0.09-0.32) competition. For deceased donor kidney transplantation, increasing market competition was significantly associated with mortality [hazard ratio (HR): 1.11, P = 0.01], graft failure (HR: 1.18, P = 0.0001), and greater use of low-quality kidneys (odds ratio = 1.39, P < 0.0001). This was not true for living donor kidney transplantation (mortality HR: 0.94, P = 0.48; graft failure HR: 0.99, P = 0.89). Competition was associated with longer waitlists (P = 0.04) but not with the number of transplants per capita in a DSA (P = 0.21). CONCLUSIONS: Increasing market competition is associated with increased patient mortality and graft failure and the use of riskier kidneys. These results may represent more aggressive transplantation and tolerance of greater risk for patients who otherwise have poor alternatives. Market competition should be better studied to ensure optimal outcomes. PMID- 25115432 TI - Association between hospital imaging use and venous thromboembolism events rates based on clinical data. AB - OBJECTIVE: The objective was to assess the presence and extent of venous thromboembolic (VTE) surveillance bias using high-quality clinical data. BACKGROUND: Hospital VTE rates are publicly reported and used in pay-for performance programs. Prior work suggested surveillance bias: hospitals that look more for VTE with imaging studies find more VTE, thereby incorrectly seem to have worse performance. However, these results have been questioned as the risk adjustment and VTE measurement relied on administrative data. METHODS: Data (2009 2010) from 208 hospitals were available for analysis. Hospitals were divided into quartiles according to VTE imaging use rates (Medicare claims). Observed and risk adjusted postoperative VTE event rates (regression models using American College of Surgeons National Surgical Quality Improvement Project data) were examined across VTE imaging use rate quartiles. Multivariable linear regression models were developed to assess the impact of hospital characteristics (American Hospital Association) and hospital imaging use rates on VTE event rates. RESULTS: The mean risk-adjusted VTE event rates at 30 days after surgery increased across VTE imaging use rate quartiles: 1.13% in the lowest quartile to 1.92% in the highest quartile (P < 0.001). This statistically significant trend remained when examining only the inpatient period. Hospital VTE imaging use rate was the dominant driver of hospital VTE event rates (P < 0.001), as no other hospital characteristics had significant associations. CONCLUSIONS: Even when examined with clinically ascertained outcomes and detailed risk adjustment, VTE rates reflect hospital imaging use and perhaps signify vigilant, high-quality care. The VTE outcome measure may not be an accurate quality indicator and should likely not be used in public reporting or pay-for-performance programs. PMID- 25115434 TI - CYP2C19*17 increases clopidogrel-mediated platelet inhibition but does not alter the pharmacokinetics of the active metabolite of clopidogrel. AB - The aim of the present study was to determine the impact of CYP2C19*17 on the pharmacokinetics and pharmacodynamics of the active metabolite of clopidogrel and the pharmacokinetics of proguanil. Thus, we conducted an open-label two-phase cross-over study in 31 healthy male volunteers (11 CYP2C19*1/*1, 11 CYP2C19*1/*17 and nine CYP2C19*17/*17). In Phase A, the pharmacokinetics of the derivatized active metabolite of clopidogrel (CAMD) and platelet function were determined after administration of a single oral dose of 600 mg clopidogrel (Plavix; Sanofi Avensis, Horsholm, Denmark). In Phase B, the pharmacokinetics of proguanil and its metabolites cycloguanil and 4-chlorphenylbiguanide (4-CPB) were determined in 29 of 31 subjects after a single oral dose of 200 mg proguanil given as the combination drug Malarone (GlaxoSmithKline Pharma, Brondby, Denmark). Significant correlations were found between the area under the time-concentration curve (AUC0 infinity ) of CAMD and both the absolute ADP-induced P2Y12 receptor-activated platelet aggregation (r = -0.60, P = 0.0007) and the percentage inhibition of aggregation (r = 0.59, P = 0.0009). In addition, the CYP2C19*17/*17 and CYP2C19*1/*17 genotype groups had significantly higher percentage inhibition of platelet aggregation compared with the CYP2C19*1/*1 subjects (geometric mean percentage inhibition of 84%, 73% and 63%, respectively; P = 0.014). Neither the absolute ADP-induced P2Y12 receptor-activated platelet aggregation, exposure to CAMD nor the pharmacokinetic parameters of proguanil, cycloguanil and 4-CPB exhibited any significant differences among the genotype groups. In conclusion, carriers of CYP2C19*17 exhibit higher percentage inhibition of platelet aggregation, but do not have significantly lower absolute P2Y12 receptor activated platelet aggregation or higher exposure to the active metabolite after a single oral administration of 600 mg clopidogrel. PMID- 25115433 TI - Nanoparticle-assisted targeted delivery of eye-specific genes to eyes significantly improves the vision of blind mice in vivo. AB - Application of viruses as a carrier, though not safe, to deliver genes to eye tissue was successful. However, a safer, nonviral, biocompatible lipid-based nanoparticle has never been tested to treat blinding eye diseases. We created an artificial virus using a nanoparticle, liposome-protamine-DNA complex (LPD), modified with a cell permeable peptide and a nuclear localization signaling (NLS) peptide, to deliver a functional gene for eye disease treatment. In the eye, a photochemical, 11-cis-retinal, allows the visual pigment rhodopsin to absorb light in the visible range. Without the photochemical, we lose the ability to see light. Retinal pigment epithelium protein 65 (Rpe65) is the key enzyme in regulating the availability of photochemical; deficiency of this gene results in a blinding eye disease. Here we show for the first time that LPD promotes efficient delivery in a cell specific-manner, and a long-term expression of Rpe65 gene to mice lacking Rpe65 gene, leading to in vivo correction of blindness. Thus, LPD nanoparticles could provide a promising, efficient, nonviral method of gene delivery with clinical applications in eye disease treatment. PMID- 25115436 TI - Latest evidence of the effects of the Mediterranean diet in prevention of cardiovascular disease. AB - The first step in the prevention of cardiovascular disease is healthy lifestyle and diet. Recent systematic reviews of observational studies ranked Mediterranean diet as the most likely dietary model to provide cardiovascular protection. This review updates the knowledge on the effects of Mediterranean diet from observational and randomized trials published in the last year. The results of the PREDIMED study, a randomized trial providing a higher level of scientific evidence than cohort studies, confirmed that the Mediterranean diet reduces the incidence of cardiovascular events. This effect may be exerted by reducing blood pressure; improving glucose metabolism, lipid profile, and lipoprotein particle characteristics; and decreasing inflammation and oxidative stress. It may also stem from a favorable interaction between diet and gene polymorphisms related to cardiovascular risk factors and events. These recent results allow us to recommend Mediterranean diet to subjects at high risk for cardiovascular disease with the highest level of scientific evidence. PMID- 25115435 TI - Expression of domains for protein-protein interaction of nucleotide excision repair proteins modifies cancer cell sensitivity to platinum derivatives and genomic stability. AB - Nucleotide excision repair (NER) is involved in the repair of DNA damage caused by platinum derivatives and has been shown to decrease the cytotoxic activity of these drugs. Because protein-protein interactions are essential for NER activity, we transfected human cancer cell lines (A549 and HCT116) with plasmids coding the amino acid sequences corresponding to the interacting domains between excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum, complementation group A (XPA), as well as ERCC1 and xeroderma pigmentosum, complementation group F (XPF), all NER proteins. Using the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and annexin V staining, we showed that transfected A549 cells were sensitized 1.2-2.2-fold to carboplatin and that transfected HCT116 cells were sensitized 1.4-5.4-fold to oxaliplatin in vitro. In addition, transfected cells exhibited modified in vivo sensitivity to the same drugs. Finally, in particular cell models of the interaction between ERCC1 and XPF, DNA repair was decreased, as evidenced by increased phosphorylation of the histone 2AX after exposure to mitomycin C, and genomic instability was increased, as determined by comparative genomic hybridization studies. The results indicate that the interacting peptides act as dominant negatives and decrease NER activity through inhibition of protein-protein interactions. PMID- 25115439 TI - Exacerbation of alopecia areata during pegylated interferon alpha-2b and ribavirin therapy, possibly due to the collapse of hair follicle immune privilege. PMID- 25115438 TI - "Vitamin D supplementation and bone health in adults with diabetic nephropathy: the protocol for a randomized controlled trial". AB - BACKGROUND: Suboptimal vitamin D status is highly prevalent in Northern communities, particularly in those patients with chronic diseases such as diabetes and chronic renal disease. Emerging literature suggests that adherence to daily vitamin D supplementation may be an important factor influencing vitamin D status and overall bone health, but compliance with therapies for bone health is a major challenge. It is unknown what level of vitamin D supplementation will ameliorate or improve suboptimal vitamin D status in patients with diabetic nephropathy or contribute to improved bone health, particularly for those living in northern climates. METHODS/DESIGN: The study purpose was to examine two different strategies of vitamin D3 supplementation; daily dosing of 2000 IU per day verses monthly dosing of 40,000 IU per month on markers of vitamin D status, bone health and to examine whether adherence, quality of life and patient satisfaction with the supplementation strategy differs between the two vitamin D strategies in adults diagnosed with diabetic nephropathy. DISCUSSION: The need for RCTs assessing higher doses of vitamin D3 supplementation at varying frequencies of administration and its impact on bone health in adults with diabetes and chronic kidney disease are needed. TRIAL REGISTRATION: ClinicalTrials.gov NCT01476501. PMID- 25115437 TI - Untargeted metabolite profiling of murine embryos to reveal metabolic perturbations associated with neural tube closure defects. AB - BACKGROUND: Neural tube closure defects (NTDs) are among the most common congenital malformation in human, typically presenting in liveborns as spina bifida. At least 240 gene mutations in mouse are known to increase the risk of NTD. There is a growing appreciation that environmental factors significantly contribute to NTD expression, and that NTDs likely arise from complex gene environment interactions. Because maternal folic acid supplementation reduces human NTD risk in some populations by 60 to 70%, it is likely that NTD predisposition is often associated with a defect in folate-dependent one-carbon metabolism. A comprehensive, untargeted metabolic survey of NTD-associated changes in embryo metabolism would provide a valuable test of this assumption. We sought to establish a metabolic profiling platform that is capable of broadly assessing metabolic aberrations associated with NTD-promoting gene mutations in early-stage mouse embryos. METHODS: A liquid chromatography/mass spectrometry based untargeted metabolite profiling platform was used to broadly identify significant differences in small molecule levels (50-1000 Da) in NTD-affected embryonic day (E) 9.5 mouse embryos (Lrp6(-) (/) (-) ) versus unaffected (Lrp6(+/+) ) control embryos. RESULTS: Results provide proof-of-principal feasibility for the broad survey of the metabolome of individual E9.5 mouse embryos and identification of metabolic changes associated with NTDs and gene mutations. Levels of 30 different metabolites were altered in association with Lrp6 gene deletion. Some metabolites link to folate-dependent one-carbon transfer reactions, as anticipated, while others await structure elucidation and pathway integration. CONCLUSION: Whole-embryo metabolomics offers the potential to identify metabolic changes in genetically determined NTD-prone embryos. PMID- 25115440 TI - Wntless (GPR177) expression correlates with poor prognosis in B-cell precursor acute lymphoblastic leukemia via Wnt signaling. AB - B-cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common childhood leukemia, with a cure rate of 80%. Nevertheless, disease relapse is the most important prognostic factor for the disease outcome. We aimed to elucidate the role of Wnt secretion-regulating protein, Wntless (Wls)/GPR177, on disease outcome in pediatric patients with BCP ALL, and assess its pathogenetic role in the regulation of the disease. Wls expression was characterized and correlated with Wnt pathway signaling in the bone marrow leukemia cells isolated from 44 pediatric patients with BCP ALL. The overexpression of Wls was detected in leukemia cells and was significantly correlated with the disease relapse and poor survival in the patients. The high expression of Wls also correlated with the Wnt expression and consequent downstream signaling activation, which was shown to provide essential proliferation, transformation and anti-apoptotic activity during leukemogenesis. These results indicated that Wls played an essential role in disease relapse and poor survival in patients with BCP ALL. Therefore, Wls may provide a potential future therapeutic target, particularly for patients who do not respond to existing therapies and suffer relapse. PMID- 25115441 TI - Approaches to integrating germline and tumor genomic data in cancer research. AB - Cancer is characterized by a diversity of genetic and epigenetic alterations occurring in both the germline and somatic (tumor) genomes. Hundreds of germline variants associated with cancer risk have been identified, and large amounts of data identifying mutations in the tumor genome that participate in tumorigenesis have been generated. Increasingly, these two genomes are being explored jointly to better understand how cancer risk alleles contribute to carcinogenesis and whether they influence development of specific tumor types or mutation profiles. To understand how data from germline risk studies and tumor genome profiling is being integrated, we reviewed 160 articles describing research that incorporated data from both genomes, published between January 2009 and December 2012, and summarized the current state of the field. We identified three principle types of research questions being addressed using these data: (i) use of tumor data to determine the putative function of germline risk variants; (ii) identification and analysis of relationships between host genetic background and particular tumor mutations or types; and (iii) use of tumor molecular profiling data to reduce genetic heterogeneity or refine phenotypes for germline association studies. We also found descriptive studies that compared germline and tumor genomic variation in a gene or gene family, and papers describing research methods, data sources, or analytical tools. We identified a large set of tools and data resources that can be used to analyze and integrate data from both genomes. Finally, we discuss opportunities and challenges for cancer research that integrates germline and tumor genomics data. PMID- 25115442 TI - Granulin-epithelin precursor interacts with heparan sulfate on liver cancer cells. AB - Granulin-epithelin precursor (GEP) is a pluripotent secretory growth factor which promotes cancer progression in a number of human cancers. However, how cancer cells interact with GEP remains unknown. In this study, we aimed to identify the cell surface-binding partner of GEP on liver cancer cells. Human recombinant GEP (rGEP) was expressed and purified to homogeneity. The rGEP was shown to trigger phosphorylation of AKT and ERK1/2 in liver cancer cells. We demonstrated cell surface attachment of rGEP, which was blocked by prebinding of platelet-derived growth factor-AA, platelet-derived growth factor-BB and fibroblast growth factor 2. Therefore, heparan sulfate (HS) had been reasoned as the binding partner of rGEP. Heparinase digestion validated the role of HS on supporting the attachment. The heparin-binding domain of GEP was mapped to RRH(555-557) in the C-terminal region. Suppression of the HS polymerase exostosin-1 reduced the rGEP binding and rGEP-mediated signaling transduction. Suppression of a specific HS proteoglycan, glypican-3, also showed a partial reduction of rGEP binding and an inhibition on rGEP-mediated activation of AKT. Furthermore, glypican-3 was shown to correlate with the expressions of GEP in clinical samples (Spearman's rho = 0.363, P = 0.001). This study identified HS, partly through glypican-3, as a novel binding partner of GEP on the surface of liver cancer cells. PMID- 25115444 TI - Blood cadmium and depressive symptoms in young adults (aged 20-39 years). AB - BACKGROUND: Genetic and environmental factors contribute to the risk of depression and several studies have noted an association between tobacco smoke and depression. Cadmium is a neurotoxicant and the main source of non occupational exposure is tobacco smoke. METHOD: We conducted a cross-sectional analysis of data from 2892 young adult (aged 20-39 years) participants of the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Multivariate logistic regressions, adjusted for age, sex, race/ethnicity, education, poverty income ratio (PIR), obesity, alcohol intake, blood lead (BPb) and smoking status, were used to analyze the association between blood cadmium (BCd) and depressive symptoms, as determined by the score on the nine-item Patient Health Questionnaire (PHQ-9). RESULTS: Individuals in the highest BCd quartile had higher odds of having depressive symptoms [odds ratio (OR) 2.79, 95% confidence interval (CI) 1.84-4.25] than those in the lowest BCd quartile. Smoking status, but not BPb, was statistically significantly associated with depressive symptoms. Stratification by smoking status found that BCd was significantly associated with depressive symptoms in both non-smokers (OR 2.91, 95% CI 1.12-7.58) and current smokers (OR 2.69, 95% CI 1.13-6.42). CONCLUSIONS: This is the first study to report an association between BCd levels and depressive symptoms using a nationally representative sample. The association of cadmium with depressive symptoms was independent of smoking status. If this association is further confirmed, the continued efforts at reducing cadmium exposures, mainly through tobacco smoking cessation programs, may decrease the incidence of depression. PMID- 25115445 TI - The role of mirabegron in overactive bladder: a systematic review and meta analysis. AB - OBJECTIVE: To present a systematic review assessing the efficacy and safety of mirabegron for overactive bladder (OAB). MATERIALS AND METHODS: A literature search was performed using the Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded. The literature reviewed included meta-analyses, randomized and nonrandomized prospective studies. We utilized mean difference (MD) to measure the mean number of incontinence episodes and the mean number of micturitions, and OAB questionnaire (OAB-q) and odds ratio (OR) to measure adverse events rates. We used the Cochrane Collaboration's Review Manager 5.1 software for statistical analysis. RESULTS: We identified six publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that mirabegron was more effective than placebo in treating OAB despite different drug dosages in the efficacy end points: mean number of incontinence episodes per 24 h (MD -0.54; 95% CI -0.63, -0.45; p = 0.001), mean number of micturitions per 24 h (MD -0.55; 95% CI -0.63, -0.47; p = 0.001), OAB-q (MD -4.49; 95% CI -6.27, 2.71; p = 0.001) and adverse events (OR 0.99; 95% CI 0.83, 1.19; p = 0.92). When compared to tolterodine, mirabegron was more effective in terms of mean number of incontinence episodes per 24 h (MD -0.25; 95% CI -0.43, -0.06; p = 0.009). However, there were no differences between mirabegron and tolterodine in mean number of micturitions per 24 h (MD -0.17; 95% CI -0.35, 0.01; p = 0.07) and OAB q (MD -1.09; 95% CI -2.51, 0.33; p = 0.13). Mirabegron also had a lower adverse reaction rate (OR 0.9; 95% CI 0.8, 1.0; p = 0.04). CONCLUSIONS: In this diverse population, mirabegron was an effective and safe pharmacologic therapy for OAB. PMID- 25115443 TI - N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis. AB - The cell metabolome comprises abundant information that may be predictive of cell functions in response to epigenetic or genetic changes at different stages of cell proliferation and metastasis. An unbiased ultra-performance liquid chromatography-mass spectrometry-based metabolomics study revealed a significantly altered metabolome for human pancreatic carcinoma PANC-1 cells with gain-of-function non-coding microRNA-1291 (miR-1291), which led to a lower migration and invasion capacity as well as suppressed tumorigenesis in a xenograft tumor mouse model. A number of metabolites, including N methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine, isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism, were elevated in miR-1291-expressing PANC-1. Notably, N-methylnicotinamide was elevated to the greatest extent, and this was associated with a sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells. In addition, expression of NNMT mRNA was inversely correlated with pancreatic tumor size in the xenograft mouse model. These results indicate that miR-1291-altered PANC-1 cell function is associated with the increase in N methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative of the extent of pancreatic carcinogenesis. PMID- 25115447 TI - Anti-adalimumab antibodies and adalimumab concentrations in psoriatic arthritis; an association with disease activity at 28 and 52 weeks of follow-up. AB - OBJECTIVES: To investigate the relationship between antidrug antibodies (ADA), adalimumab concentrations and clinical response in patients with psoriatic arthritis (PsA) during 52 weeks of follow-up. METHODS: This prospective cohort study included 103 consecutive patients with PsA. Disease Activity Score of 28 joints (DAS28), Erythrocyte Sedimentation Rate, C reactive protein and Psoriasis Area and Severity Index were assessed. Adalimumab concentrations and ADA were measured in serum trough samples, using an ELISA and a radio immunoassay, respectively. RESULTS: Adalimumab concentrations were significantly lower at 28 and 52 weeks in patients with detectable ADA compared with patients without detectable ADA (at week 28: 1.3 mg/L (IQR 0.0-3.2) versus 8.7 mg/L (IQR 5.7 11.5), p<0.001; at week 52: 0.9 mg/L (IQR 0.0-2.9) vs 9.4 mg/L (IQR 5.7-12.1), p=0.0001). DAS28 at 28 weeks (2.16 vs 2.95, p=0.023) and 52 weeks (2.19 vs 2.95, p=0.024) showed a significant difference; patients with detectable ADA had a poorer clinical outcome than patients without. CONCLUSIONS: Patients with detectable ADA had lower adalimumab concentrations and a significantly poorer clinical outcome compared with patients in whom ADA were not detected. PMID- 25115448 TI - Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA. AB - OBJECTIVE: To determine whether there is an additive effect of anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) on the number and size of bone erosions in patients with rheumatoid arthritis (RA) METHODS: 242 patients with RA received high-resolution peripheral quantitative CT (HR-pQCT) scans of the metacarpophalangeal joints. Demographic and disease-specific parameters including ACPA and RF levels were recorded from all patients. Erosion numbers and their size were assessed in 238 patients at 714 individual joints (MCP 2, 3 and 4) and 5712 sites (each 4 quadrants in metacarpal heads and phalangeal bases). The volume of erosions was calculated by a semiellipsoid formula. RESULTS: Of the 238 patients, 112 patients showed RF and ACPAs (ACPAs+RF+), 28 only RF (RF+), 29 only ACPAs (ACPA+) and 69 were antibody negative (NEG). Erosion number and size were highest in RF+ACPAs+ patient group with significant differences compared with NEG patients with respect to erosion number (p=0.001) and to ACPA-negative patients with respect to erosion size (p<0.001). Results maintained significance in a linear mixed model showing ACPAs+RF+ status and disease duration being associated with higher number (p=0.017 and p=0.005, respectively), and larger size (p=0.014 and p=0.013, respectively) of bone erosions. Furthermore, erosion size was influenced by the presence and titre of RF only in ACPA-positive patients with RA but not in ACPA-negative patients. CONCLUSIONS: ACPAs and RF show an additive effect on erosion number and erosion size. Concomitant presence of ACPAs and RF is associated with higher erosive disease burden in patients with RA. Furthermore, RF influences erosion size only in ACPA-positive but not in ACPA negative patients. PMID- 25115450 TI - Of text and gene--using text mining methods to uncover hidden knowledge in toxicogenomics. AB - BACKGROUND: Toxicogenomics studies often profile gene expression from assays involving multiple doses and time points. The dose- and time-dependent pattern is of great importance to assess toxicity but computational approaches are lacking to effectively utilize this characteristic in toxicity assessment. Topic modeling is a text mining approach, but may be used analogously in toxicogenomics due to the similar data structures between text and gene dysregulation. RESULTS: Topic modeling was applied to a very large toxicogenomics dataset containing microarray gene expression data from >15,000 samples associated with 131 drugs tested in three different assay platforms (i.e., in vitro assay, in vivo repeated dose study and in vivo single dose experiment) with a design including multiple doses and time points. A set of "topics" which each consist of a set of genes was determined, by which the varying sensitivity of three assay systems was observed. We found that the drug-dependent effect was more pronounced in the two in vivo systems than the in vitro system, while the time-dependent effect was most strongly reflected in the in vitro system followed by the single dose study and lastly the repeated dose experiment. The dose-dependent effect was similar across three assay systems. Although the results indicated a challenge to extrapolate the in vitro results to the in vivo situation, we did notice that, for some drugs but not for all the drugs, the similarity in gene expression patterns was observed across all three assay systems, indicating a possibility of using in vitro systems with careful designs (such as the choice of dose and time point), to replace the in vivo testing strategy. Nonetheless, a potential to replace the repeated dose study by the single-dose short-term methodology was strongly implied. CONCLUSIONS: The study demonstrated that text mining methodologies such as topic modeling provide an alternative method compared to traditional means for data reduction in toxicogenomics, enhancing researchers' capabilities to interpret biological information. PMID- 25115449 TI - Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin. AB - OBJECTIVE: Allopurinol, an antihyperuricaemic agent, is one of the common causes of life-threatening severe cutaneous adverse reactions (SCAR), including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The prognostic factors for allopurinol related SCAR remain unclear. This study aimed to investigate the relationship of dosing, renal function, plasma levels of oxypurinol and granulysin (a cytotoxic protein of SJS/TEN), the disease severity and mortality in allopurinol-SCAR. METHODS: We prospectively enrolled 48 patients with allopurinol-SCAR (26 SJS/TEN and 22 DRESS) and 138 allopurinol-tolerant controls from 2007 to 2012. The human leucocyte antigen (HLA)-B*58:01 status, plasma concentrations of oxypurinol and granulysin were determined. RESULTS: In this cohort, HLA-B*58:01 was strongly associated with allopurinol-SCAR (p<0.001, OR (95% CI) 109 (25 to 481)); however, the initial/maintenance dosages showed no relationship with the disease. Poor renal function was significantly associated with the delayed clearance of plasma oxypurinol, and increased the risk of allopurinol-SCAR (p<0.001, OR (95% CI) 8.0 (3.9 to 17)). Sustained high levels of oxypurinol after allopurinol withdrawal correlated with the poor prognosis of allopurinol-SCAR. In particular, the increased plasma levels of oxypurinol and granulysin linked to the high mortality of allopurinol-SJS/TEN (p<0.01), and strongly associated with prolonged cutaneous reactions in allopurinol-DRESS (p<0.05). CONCLUSIONS: Impaired renal function and increased plasma levels of oxypurinol and granulysin correlated with the poor prognosis of allopurinol-SCAR. Allopurinol prescription is suggested to be avoided in subjects with renal insufficiency and HLA-B*58:01 carriers. An early intervention to increase the clearance of plasma oxypurinol may improve the prognosis of allopurinol-SCAR. PMID- 25115451 TI - Enhanced aqueous dissolution of a DNAPL source to characterize the source strength function. AB - Simplified analytical solutions, developed as source strength functions (SSFs), are capable of describing the temporal dissolution of nonaqueous phase liquids in groundwater, which is useful for predicting source longevity and can serve as a guide for remedial activities. Here, SSF parameters were estimated by fitting enhanced aqueous dissolution data from a flow cell consisting of three injection and four extraction wells to analytical dissolution models (power law model (PLM) and equilibrium streamtube model (EST)) at a trichloroethene (TCE) contaminated site, Alameda Point, California. Both the PLM and the EST model were able to characterize the observed aqueous TCE dissolution during enhanced water flooding. Additional field activities conducted at the site included soil core collection, a recirculated partitioning tracer test, passive flux meter transects, and push pull tracer tests. The additional site characterization data were used to independently estimate the observed SSF parameters using information such as the TCE mass, distribution and porous media heterogeneity. The exponential decay model (a subset of the PLM) accurately predicted the enhanced dissolution, likely because the site was significantly aged (most of the mass in the plume rather than in the source zone) or middle stage, and the mass in the source zone could be approximately estimated. The EST tracer-based model, when combined with data from the recirculated partitioning tracer test, soil cores, and the push-pull tracer test, was capable of accurately predicting the observed aqueous dissolution. The mass in the source zone and the fraction of contaminated flowpaths were the most important site characteristics, requiring the greatest accuracy to predict aqueous dissolution. Establishing steady state dissolution was essential to provide a more accurate estimate of the fraction contaminated and high resolution data from soil cores in the source zone were needed to estimate the mass present. PMID- 25115452 TI - Photoinduced skeletal rearrangement of diarylethenes comprising oxazole and phenyl rings. AB - A novel photochemical rearrangement of diarylethenes bearing oxazole and benzene derivatives as aryl moieties that results in the formation of polyaromatic systems was investigated. The mechanism of the transformation includes photocyclization, sequential [1,9] and [1,3]-hydrogen shifts, as well as a lateral oxazole ring-opening process. It was shown that this reaction can be an effective synthetically preparative method for the preparation of naphthalene (polyaromatic) derivatives. PMID- 25115453 TI - Quality improvements of cell membrane chromatographic column. AB - Cell Membrane Chromatography (CMC) is a biological affinity chromatographic method using a silica stationary phase covered with specific cell membrane. However, its short life span and poor quality control was highlighted in a lot of research articles. In this study, special attention has been paid to the disruption, cell load and packing procedure in order to improve the quality of the CMC columns. Hereto, two newly established CMC models, HSC-T6/CMC and SMMC 7721/CMC have been developed and used in this research project. The optimization of the abovementioned parameters resulted in a better reproducibility of the retention time of the compound GFT (RSD<10%) and improved significantly the quality of the CMC columns. 3.5*10(7)cells were the optimal cell load for the preparation of the CMC columns, the disruption condition was optimized to 5 cycles (400W and 20s interval per cycle) by an ultrasonic processor reducing the total time of cell disruption to 1.5min and the packing flow rate was optimized by applying a linear gradient program. Additionally, 4% paraformaldehyde (PFA) was employed to improve the column quality and prolong the column life span. The results showed that the retention time was longer with PFA treated columns than the ones obtained with the control groups. PMID- 25115454 TI - Alternative sorbents for the dispersive solid-phase extraction step in quick, easy, cheap, effective, rugged and safe method for extraction of pesticides from rice paddy soils with determination by liquid chromatography tandem mass spectrometry. AB - The clean-up step is essential to reduce interferences, improve quantification and help to maintain the integrity of the chromatographic system when working with complex matrices. In this study, alternative materials were evaluated as sorbents in the dispersive solid-phase extraction (D-SPE) for the determination and extraction of seventeen pesticides from rice paddy soil samples by the quick, easy, cheap, effective, rugged and safe (QuEChERS) method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chitin, chitosan, diatomaceous earth and PSA were compared in terms of extraction efficiency and matrix effect. The best results were achieved when chitosan was used. Quantification limits ranged from 0.1 to 100MUgkg(-1). Calibration curves showed correlation coefficient values higher than 0.98. Results of accuracy and precision in the spiked soil samples between 60% and 120%, with a relative standard deviation lower than 20%, were reached for 15 out of 17 pesticides. The matrix effect was evaluated and only one compound was influenced by the matrix components, showing medium effect. Results showed that alternative materials are more effective and less expensive than traditional sorbents which have been usually employed, i.e., they may be used in the D-SPE step during the extraction of pesticides from rice paddy soils. PMID- 25115455 TI - 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as an enantioseparation enhancer for fluorescence chiral derivatization-liquid chromatographic analysis of dl-lactic acid. AB - This paper reports a novel fluorescence chiral derivatization-liquid chromatography (LC) method for the analysis of d- and l-lactic acids (LAs) using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as an enantioseparation enhancer. In this method, the dl-LAs were fluorescently derivatized with (S)-(+)-4-(N,N-dimethylaminosulfonyl)-7-(3-aminopyrrolidin-1-yl) 2,1,3-benzoxadiazole [(S)-(+)-DBD-APy] in the presence of DMT-MM as a condensing agent. These conditions resulted in the hydroxyl group of the LA derivative being etherified by the triazine unit of DMT-MM, producing sterically bulky diastereoisomers. The resulting fluorescent diastereoisomers of d- and l-LAs could be discriminated and successfully enantioseparated through reversed-phase LC. The enhancement effect of the derivatization agent DMT-MM when using seven other commercially available chiral amines was also demonstrated. Finally, this method was successfully applied to quantification of dl-LAs in foodstuffs (yogurts and fermented milk drinks). PMID- 25115456 TI - Simple semi-automated portable capillary electrophoresis instrument with contactless conductivity detection for the determination of beta-agonists in pharmaceutical and pig-feed samples. AB - An inexpensive, robust and easy to use portable capillary electrophoresis instrument with miniaturized high-voltage capacitively coupled contactless conductivity detection was developed. The system utilizes pneumatic operation to manipulate the solutions for all flushing steps. The different operations, i.e. capillary flushing, interface rinsing, and electrophoretic separation, are easily activated by turning an electronic switch. To allow the analysis of samples with limited available volume, and to render the construction less complicated compared to a computer-controlled counterpart, sample injection is carried out hydrodynamically directly from the sample vial into the capillary by manual syphoning. The system is a well performing solution where the financial means for the highly expensive commercial instruments are not available and where the in house construction of a sophisticated automated instrument is not possible due to limited mechanical and electronic workshop facilities and software programming expertise. For demonstration, the system was employed successfully for the determination of some beta-agonists, namely salbutamol, metoprolol and ractopamine down to 0.7ppm in pharmaceutical and pig-feed sample matrices in Vietnam. PMID- 25115457 TI - Hecogenin acetate inhibits reactive oxygen species production and induces cell cycle arrest and senescence in the A549 human lung cancer cell line. AB - Cellular and molecular mechanisms related to lung cancer have been extensively studied in recent years, but the availability of effective treatments is still scarce. Hecogenin acetate, a natural saponin presenting a wide spectrum of reported pharmacological activities, has been previously evaluated for its anticancer/antiproliferative activity in some in vivo and in vitro models. Here, we investigated the effects of hecogenin acetate in a human lung cancer cell line. A549 non-small lung cancer cells were exposed to different concentrations of hecogenin acetate and reactive species production, ERK1/2 activation, matrix metalloproteinase expression, cell cycle arrest and cell senescence parameters were evaluated. Hecogenin acetate significantly inhibited increase in intracellular reactive species production induced by H2O2. In addition, hecogenin acetate blocked ERK1/2 phosphorylation and inhibited the increase in MMP-2 caused by H2O2. Treatment with hecogenin acetate induced G0/G1-phase arrest at two concentrations (75 and 100 uM, 74% and 84.3% respectively), and increased the staining of senescence-associated beta -galactosidase positive cells. These data indicate that hecogenin acetate is able to exert anti-cancer effects by modulating reactive species production, inducing cell cycle arrest and senescence and also modulating ERK1/2 phosphorylation and MMP-2 production. PMID- 25115458 TI - Association between rs12970134 Near MC4R and adiposity indexes in a homogenous population of Caucasian schoolchildren. AB - BACKGROUND: To assess whether previously identified obesity-susceptibility loci were associated with overweight/obesity risk in a homogeneous population of Caucasian schoolchildren and whether these associations varied with age. METHODS: Seven hundred and forty-five schoolchildren (353 boys, mean age: 8.3 +/- 1.4 years) underwent anthropometric assessments. A saliva sample was collected for DNA extraction and assessment of 19 single-nucleotide polymorphisms previously associated with obesity. RESULTS: Only the rs12970134 in the MC4R gene was significantly associated with overweight/obesity risk, with a higher frequency of the AA risk genotype in children with a BMI >85th (8.3%) than in those with a BMI <85th percentile (3.0%), p = 0.001; odds ratio (95% CI) of 1.544 (1.192-1.998), p = 0.001, after adjusting for age, sex and pubertal stage. BMI standard deviation scores (SDS) and waist-to-height ratio (W/Hr) progressively increased across the rs12970134 genotypes (GG vs. AG vs. AA): BMI SDS, p = 0.004; W/Hr, p = 0.009. When dividing the study population into two groups based on the median age of participants (8.3 years), the differences in BMI SDS and W/Hr across the MC4R genotypes persisted only in children older than 8.3 years. CONCLUSIONS: In a population of Caucasian schoolchildren, the rs12970134 MC4R variant was significantly associated with excess body weight, particularly in children older than 8 years of age. PMID- 25115459 TI - Propofol versus traditional sedative agents for endoscopic submucosal dissection. AB - BACKGROUND AND AIM: Propofol has been suggested to be superior to benzodiazepines when used as a sedative agent for endoscopic examination. The aim of the present study was to systematically evaluate the safety and efficacy of propofol sedation for endoscopic submucosal dissection (ESD). METHODS: PubMed, the Cochrane library, and the Igaku-Chuo-Zasshi database were searched in order to identify randomized trials eligible for inclusion in the systematic review. Data from the eligible studies were combined to calculate pooled odds ratios (OR) of developing restlessness, full awakening at 1 h post-ESD, hypoxia, and hypotension. RESULTS: We identified three randomized trials (298 patients) from the database search. Compared with traditional sedative agents, the pooled OR of restlessness and full awakening at 1 h post-ESD with propofol sedation were 0.41 (95% confidence interval [CI]: 0.21-0.81) and 8.59 (95% CI: 4.29-17.2), respectively, without significant heterogeneity. Compared with traditional sedative agents, the pooled OR of hypoxia and hypotension with propofol sedation were 1.13 (95% CI: 0.58 2.21) and 0.92 (95% CI: 0.25-3.41), respectively, indicating no significant differences between the groups. CONCLUSION: Propofol sedation during ESD is more effective as compared with traditional sedative agent. The risk of complications is similar. PMID- 25115460 TI - A systematic review of online youth mental health promotion and prevention interventions. AB - The rapid growth in the use of online technologies among youth provides an opportunity to increase access to evidence-based mental health resources. The aim of this systematic review is to provide a narrative synthesis of the evidence on the effectiveness of online mental health promotion and prevention interventions for youth aged 12-25 years. Searching a range of electronic databases, 28 studies conducted since 2000 were identified. Eight studies evaluating six mental health promotion interventions and 20 studies evaluating 15 prevention interventions were reviewed. The results from the mental health promotion interventions indicate that there is some evidence that skills-based interventions presented in a module-based format can have a significant impact on adolescent mental health, however, an insufficient number of studies limits this finding. The results from the online prevention interventions indicate the significant positive effect of computerized cognitive behavioral therapy on adolescents' and emerging adults' anxiety and depression symptoms. The rates of non-completion were moderate to high across a number of studies. Implementation findings provide some evidence that participant face-to-face and/or web-based support was an important feature in terms of program completion and outcomes. Additional research examining factors affecting exposure, adherence and outcomes is required. The quality of evidence across the studies varied significantly, thus highlighting the need for more rigorous, higher quality evaluations conducted with more diverse samples of youth. Although future research is warranted, this study highlights the potential of online mental health promotion and prevention interventions in promoting youth wellbeing and reducing mental health problems. PMID- 25115461 TI - Two cases of ulcerative colitis developing in rheumatoid arthritis patients during abatacept therapy. PMID- 25115462 TI - Collagen-functionalised titanium surfaces for biological sealing of dental implants: effect of immobilisation process on fibroblasts response. AB - The clinical success of a dental implant requires not only an optimum osseointegration, but also the development of a biological sealing; i.e., a soft tissue seal around the transmucosal part of the implant. A promising approach to improve the biological seal of dental implants is the biomimetic modification of titanium surfaces with proteins or peptides that have specific cell-binding moieties. In this work we investigated the process of immobilising collagen on smooth and rough titanium surfaces and its effect on human dermal fibroblast (HDF) cell response. Titanium samples were activated by either oxygen plasma or acid etching to generate a smooth or nanorough surface, respectively. Subsequently, collagen grafting was achieved by either physisorption or covalent bonding through organosilane chemistry. The biofunctionalised titanium samples were then tested for stability and characterised by fluorescent labelling, wettability, OWLS and XPS studies. Biological characterisation was also performed through HDF adhesion, proliferation and gene expression. Covalent-bonded collagen showed higher stability than physisorbed collagen. A significant overexpression of the genes involved in fibroblast activation and extracellular matrix remodelling was observed in the collagen-coated surfaces. This effect was more pronounced on smooth than on rough surfaces. Immobilised collagen on the smooth plasma-treated surfaces favoured both fibroblast adhesion and activation. This study provides essential information for the design of implants with optimal biological sealing, a key aspect to avoid peri-implantitis and ensure long lasting implant fixation. PMID- 25115463 TI - [Women are more sedentary than men: are they lazy or discriminated?]. PMID- 25115464 TI - [The epidemiologists and the participant-led science]. PMID- 25115465 TI - [Who is monitoring air pollution in Florence?]. PMID- 25115466 TI - [Science and law in courts]. AB - Science and law can be seen as the main creators of orders and rules in knowledge based societies. These relations are particularly delicate in domains where scientific uncertainty and probabilistic causality are more frequently involved, such as environment and health. The decision of the Court of Florence (Tuscany Region, Northern Italy) (Second Criminal Division, 3217/2010, 17th May 2010) - here analysed - deals with the uncertain correlations between PM10 and health. The criminal law case involved some public officers in Tuscany, indicted for having failed to adopt the adequate measures to keep PM10 levels within the limits set by European Directive 2008/50/EC on air quality. In arguing that accusations were ill-founded, the Court, while invoking the validity of science, deliberately chose the scientific evidence relevant to drawing specific legal consequences. Meteorological phenomena are considered as the single determinant of high levels of PM10; their uncertainty is framed as absolute unpredictability and ungovernability, and from these flaws non-responsibility. The concept of coproduction is applied as a useful critical tool to open up the complex relationships between science and law by showing how scientific and legal concepts generate and influence each other even when legal regulations claims to be neutrally and objectively science-based. PMID- 25115467 TI - [Noise and air pollution: the effect of airports on the health of residents]. PMID- 25115468 TI - [Relationship between surgical volumes and 30-day mortality in patients with oesophagus and stomach cancer: a review of the literature and metanalysis]. AB - OBJECTIVES: to analyse the relationship between annual hospital volumes of surgery for oesophageal and gastric cancer and 30-day mortality. DESIGN: a systematic review of the literature has been carried out on these topics by searching Medline for the years 1998-2012 and using two ad hoc search strings. For oesophageal cancer, the most recent and best quality systematic review was updated by including further studies, and then a metanalysis was carried out. For gastric cancer, two different metanalyses on low and high volumes were performed. RESULTS: regarding oesophageal carcinoma, the study confirmed the association between 30-day mortality and the number of annual hospital interventions for this pathology. As for stomach cancer, the two metanalyses confirmed the role of high volume surgery in reducing the outcome considered. CONCLUSIONS: this study confirms the association between short-term outcomes and the number of annual hospital interventions for oesophageal and gastric cancer. The results obtained may be important for health care policy makers and administrators/managers in order to improve quality of care for patients with oesophageal or stomach cancer. PMID- 25115469 TI - [Avoidable mortality in Tuscany Region (Central Italy) from 1987 to 2008]. AB - OBJECTIVE: to evaluate the impact of avoidable mortality (AM) on the changes in life expectancy at birth (LE) in Tuscany Region (Central Italy) in two periods (1987-1989 and 2006-2008). SETTING AND PARTICIPANTS: a list of AM causes previously published was used. The AM were divided into two groups: AM by Health Policy Interventions (HPI), AM by Health System Interventions (HSI). MAIN OUTCOME MEASURES: years of potential life lost (PYLLs), rates of PYLL standardized on the European population (TSPYLLs), and LE were examined. RESULTS: in 2006-2008, LE increased with a gain of 5.2 in men and 3.8 in women in comparison to 1987-1989 LE (respectively 79 and 84,9 years). If AM did not have occurred, LE would have further increased of 2 years in men and 1.5 in women. AM recorded a 39% decrease: from 25.3% of overall mortality in men in 1987-1989 to 16.1% in 2006-2008; in women from 14.3% to 8.4%. Injury/poisoning and lung cancer are the most frequent IPP. The only increasing AM is lung cancer in women. Disentangling LE increases by group of causes, 25% of the increases in 2006- 2008, compared to 1987-1989, was attributable to HSI reduction, and 4% in women and 16% in men to HPI reduction. CONCLUSIONS: AM recorded a 39% decrease from 1987-1989 to 2006-2008 in Tuscany. In 2006-2008, about one third of LE increase in women and 2/5 in men was attributable to AM decrease, while 2/3 in women and 3/5 in men to increased survival in eldest people. PMID- 25115470 TI - [Tuberculosis in the districts of Kamez and Vlore (Albania) in the early 2000s]. AB - OBJECTIVES: evaluation of tuberculosis (TB) rates and treatment outcomes in two Albanian districts of similar population, but different disease diffusion: Kamez and Vlore. DESIGN AND PARTICIPANTS: retrospective observational study of all the medical charts of not-HIV+ TB patients in Vlore from 2002 to 2011, and in Kamez from 2004 to 2011. MAIN OUTCOME MEASURES AND RESULTS: at Vlore the cases observed were 120 cases (mean age: 43 years, 68% males); the incidence rate was substantially stable in the study period, with 8 cases/100,000 inhabitants/year, and, overall, lower (p <0.001) than at Kamez. The TB cases founded were 160 (mean age: 45 years, 61% males) at Kamez, with decreasing incidence rate (Annual Percent Change - APC: -12%; p =0.00022), from 30-42/100,000 inhabitants/year in 2004- 2005 to 16.4/100,000 in 2011. New and retreated cases were, respectively, 96.7% and 3.3% at Vlore, and 96.25% and 3.75% at Kamez. Pulmonary TB was 75% at Vlore and 65% at Kamez. Most cases with pulmonary TB (79%) were microbiologically confirmed. Overall, successful treatments and relapses were respectively observed in 89% and 3% of cases with no drug resistance CONCLUSIONS: in the first years of the third millennium, TB rates remain different between the two studied Albanian districts, but with a significant reduction in the area with greater baseline incidence (Kamez); overall disease control seems to be good. PMID- 25115472 TI - [Hospitalization study on a cohort of families applying for tenement houses in Florence (Tuscany Region, Central Italy)]. AB - OBJECTIVES AND DESIGN: to evaluate the morbidity of a materially deprived population of family members applying for public tenement houses in Florence, Central Italy, in the period 1977-2001. SETTING AND PARTICIPANTS: all yearly first hospital admissions concerning 4,773 persons resident in Florence who applied for tenement houses to local public bodies during 1997-2001 were collected. MAIN OUTCOME MEASURES: gender specific age-standardized hospitalization ratios (SHR) for all causes and cause-specific hospital admissions during 2001- 2005. The expected cases were calculated using as reference gender, age and cause specific hospitalization rates of Tuscany population for the 2001-2005 period. RESULTS: 2,777 hospital admissions were registered. Statistically significant excesses of standardized hospitalization ratio were observed in both genders for all causes (males: SHR 1.14, 95%CI 1.07 1.20; females: SHR 1.22, 95%CI 1.16-1.28), mental disorders (males: SHR 2.19, 95%CI 1.71- 2.76; females: SHR 1.77, 95%CI 1.35-2.27) and respiratory diseases (males: SHR 1.25, 95%CI 1.05-1.47; females: SHR 1.33, 95%CI 1.09-1.60). Other excesses were observed for endocrine, metabolic and immunity disorders only in males (SHR 1.38, 95%CI 1.04-1.79), and for injuries and poisoning only in females (SHR 1.24, 95%CI 1.03-1.48). Statistical significant deficits were observed for neoplasm and for diseases of circulatory system in both genders, and for diseases of the musculoskeletal system and connective tissue in males. CONCLUSION: the results, consistent with the available evidences on causes of illness in disadvantaged groups, point to the importance of built environment and adequate housing in reducing health inequalities. PMID- 25115471 TI - [A comparative analysis between regional mesothelioma registries and cancer registries: results of the ReNaM-AIRTUM project]. AB - OBJECTIVES: to assess the agreement on row data and incidence rates between regional mesothelioma registries (CORs) and population cancer registries (CRs) in Italy, and to contribute in harmonizing the procedures used in identifying the date of incidence and the morphology of mesothelioma cases. SETTING E PARTICIPANTS: the mesothelioma cases registered by 19 CRs and by 9 out of 19 CORs were included in the study. Some CORs were not able to participate in the study, because there were no active CRs in their areas. MAIN OUTCOME MEASURES: agreement on cases defined as mesotheliomas by the two types of registries; Cohen's k was used for the evaluation of the agreement on morphology on specific mesothelioma (ICD-O-3 90513-90533) and mesothelioma not otherwise specified (NOS) (ICD-O-3 90503); instead, Odds Ratio was calculated to evaluate the direction of the discrepancy. Difference among incidence rates were calculated using data collected by the two types of registries. It was also made a comparison between dates of incidence. RESULTS: the comparison among the registered data by the two different types of registry showed a high concordance (>80%), especially in the areas where there is a continuous exchange of data. Only in a few areas a lower concordance was observed. The agreement between specific and non-specific morphology showed a fairly wide range and lower values than the calculation of the positive agreement. CORs used the specific morphology (ICD-O-3 90503-90533) with higher frequency compared to CRs. The CRs incidence standardized rates are higher when only cases defined as "certain " by ReNaM are considered; on the opposite the CORs rates are higher when all cases defined as "certain, probable and possible" are considered. CONCLUSIONS: the study permitted to compare and bring out the different procedures used in identifying the date of incidence of cases and morphology definition. This represents a first step of a cooperative discussion process among the involved registries: the working group hope it will end with the implementation of shared guidelines. PMID- 25115473 TI - [Occupational injury risk in immigrant workers in Italy: differences in work characteristics and age]. AB - OBJECTIVES: to describe occupational injury risk, comparing regular foreign workers with Italians, by main work characteristics and age. DESIGN: analysis of incidence and risk of total and severe occupational injury by Country of birth, stratified by economic activity, skill level, geographical area of work, firm size and age. SETTING AND PARTICIPANTS: sample of 7% of workers registered in the Italian National Institute of Social Insurance (INPS) database. The workers considered were male private sector employees aged from 16 to 55 years old who worked between 2000 and 2005 as apprentice or blue collar. Two groups were distinguished: immigrants from high migratory pressure Countries (PFPM) and immigrants from high-income Countries (PSA; Italians comprised). The three main nationalities considered were the most relevant in Italy: Moroccans, Albanians, and Romanians. MAIN OUTCOME MEASURES: all occupational injuries; severe occupational injuries based on the type of damage. RESULTS AND CONCLUSIONS: PFPM workers have a higher risk of injury compared to PSA both for total (Relative Risk - RR: 1.45) and severe ones (RR: 1.56), particularly in engineering (RR: 1.64) and trade (RR: 1.61). Moroccans have always the greatest risks (RR: 1.86); Romanians are protected on total injuries (RR: 0.80), but have excess of risk of severe injuries (RR: 1.31). Among young people there aren't differences by Country of birth, but the rate decreases as age increases in PSA, while in PFPM it increases as age increases. In this study, injury risk in regular foreign workers were measured more accurately than official statistics: Whip-Salute database can provide useful information for planning prevention programmes of immigrant work-related injuries. PMID- 25115474 TI - [Updating of the prevalence of congenital anomalies among resident births in the Municipality of Gela (Southern Italy)]. AB - OBJECTIVES: to update the prevalence of congenital anomalies in the Municipality of Gela (Southern Italy), in particular to verify whether the previously reported high prevalence of hypospadias was confirmed. DESIGN: study on prevalence at birth of congenital anomalies by retrieving information from multiple sources. SETTING AND PARTICIPANTS: in the Municipality of Gela it is localized a site of national interest for environmental remediation (SIN). Data of residents born in the Municipality of Gela in 2003-2008 were recovered from hospital records, local and regional archives, Sicilian registry of congenital malformations database, hospital admissions at medical and surgical hospitals in Catania. For comparison, European (EUROCAT), Tuscany and Emilia-Romagna registries data have been used. MAIN OUTCOME MEASURES: congenital anomalies, divided into confirmed anomalies, minor anomalies, uncertain conditions, classified by large groups and specific anomalies. RESULTS: statistically significant excesses emerge with respect to the references for genital anomalies, and for urinary and total anomalies including not-specified diagnoses. For cardiovascular and limb anomalies (including not specified clubfoot), the excess is significant only in comparison with Italian figures. The prevalence of hypospadias of 46.7/10,000 shows statistically significant excesses compared to European and Italian reference values, of 1.7 and 2.3 times, respectively. CONCLUSION: retrospective recovery of data produced incompleteness of cases and poor diagnostic definition. The epidemiological picture is more reliable for congenital anomalies less susceptible to termination of pregnancy. The study confirms a high prevalence of hypospadias, estimated between the value observed in the previous twelve-year study and the one reported for the area of Priolo-Augusta-Melilli for the years 1990-1998; and higher than those reported in literature, with sporadic exceptions. The observed data, as well as the documented presence in the environment and in biological fluids of dangerous pollutants in periconceptional exposures, support a plausibility of multifactorial aetiology for hypospadias. The environmental risk should not be neglected in the decisions of primary prevention. PMID- 25115476 TI - [Airport related air pollution and health effects]. AB - Airport is an extremely complex emission source of airborne pollutants that can have a significant impact on the environment. Indeed, several airborne chemicals emitted during airport activities may significantly get worse air quality and increase exposure level of both airport workers and general population living nearby the airports. In recent years airport traffic has increased and consequently several studies investigated the association between airport-related air pollution and occurrence of adverse health effects, particularly on respiratory system, in exposed workers and general population resident nearby. In this context, we carried out a critical evaluation of the studies that investigated this correlation in order to obtain a deeper knowledge of this issue and to identify the future research needs. Results show that the evidence of association between airport-related air pollution and health effects on workers and residents is still limited. PMID- 25115477 TI - [Air pollution in an urban area nearby the Rome-Ciampino city airport]. AB - OBJECTIVES: to assess air pollution spatial and temporal variability in the urban area nearby the Ciampino International Airport (Rome) and to investigate the airport-related emissions contribute. DESIGN AND SETTING: the study domain was a 64 km2 area around the airport. Two fifteen-day monitoring campaigns (late spring, winter) were carried out. Results were evaluated using several runs outputs of an airport-related sources Lagrangian particle model and a photochemical model (the Flexible Air quality Regional Model, FARM). MAIN OUTCOME MEASURES: both standard and high time resolution air pollutant concentrations measurements: CO, NO, NO2, C6H6, mass and number concentration of several PM fractions. 46 fixed points (spread over the study area) of NO2 and volatile organic compounds concentrations (fifteen days averages); deterministic models outputs. RESULTS: standard time resolution measurements, as well as model outputs, showed the airport contribution to air pollution levels being little compared to the main source in the area (i.e. vehicular traffic). However, using high time resolution measurements, peaks of particles associated with aircraft takeoff (total number concentration and soot mass concentration), and landing (coarse mass concentration) were observed, when the site measurement was downwind to the runway. CONCLUSIONS: the frequently observed transient spikes associated with aircraft movements could lead to a not negligible contribute to ultrafine, soot and coarse particles exposure of people living around the airport. Such contribute and its spatial and temporal variability should be investigated when assessing the airports air quality impact. PMID- 25115478 TI - [Airports and air quality: a critical synthesis of the literature]. AB - This work reviewed existing literature on airport related activities that could worsen surrounding air quality; its aim is to underline the progress coming from recent-year studies, the knowledge emerging from new approaches, the development of semi-empiric analytical methods as well as the questions still needing to be clarified. To estimate pollution levels, spatial and temporal variability, and the sources relative contributions integrated assessment, using both fixed point measurement and model outputs, are needed. The general picture emerging from the studies was a non-negligible and highly spatially variable (within 2-3 km from the fence line) airport contribution; even if it is often not dominant compared to other concomitant pollution sources. Results were highly airport-specific. Traffic volumes, landscape and meteorology were the key variables that drove the impacts. Results were thus hardly exportable to other contexts. Airport related pollutant sources were found to be characterized by unusual emission patterns (particularly ultrafine particles, black carbon and nitrogen oxides during take off); high time-resolution measurements allow to depict the rapidly changing take off effect on air quality that could not be adequately observed otherwise. Few studies used high time resolution data in a successful way as statistical models inputs to estimate the aircraft take-off contribution to the observed average levels. These findings should not be neglected when exposure of people living near airports is to be assessed. PMID- 25115479 TI - [Arsenic contamination in Italy: a comment on the SEpiAs study]. PMID- 25115475 TI - [Health impact assessment of airport noise on people living nearby six Italian airports]. AB - BACKGROUND: aircraft noise has been associated with several health effects. Because of the great success of low-cost flights, small airports have been turned into international airports thus exposing nearby residents to an increase in noise levels and potential disturbances and health disorders. OBJECTIVE: to estimate the exposure levels and evaluate the health impact of aircraft noise on residents nearby six airports in Italy (Rome: Ciampino; Milan: Linate and Malpensa; Pisa; Turin; Venice) focusing on hypertension, acute myocardial infarction (AMI), annoyance and sleep disturbances. METHODS: residents in the local Municipalities considered at 31.12.2010 were included in the study and their addresses were geocoded. Aircraft noise exposure in 2011 was defined using the Integrated Noise Model linked to each participant's address. Lden (<55, 55 60, 61-65, 65-70 dB), Lnight, Leq (day and night) were calculated. Available exposure-response relationships were used to estimate the number of additional cases of hypertension, AMI, annoyance and sleep disturbances in the local population. RESULTS: 73,272 persons exposed to aircraft noise levels >55dB were considered: 55,915 (76.3%) were exposed to 55-60 dB; 16,562 (22.6%) to 60-65 dB; 795 (1.2%) to 65-70 dB. Exposure to aircraft noise levels above 55 dB was estimated to be responsible each year of 4,607 (95%CI 0-9,923) additional cases of hypertension; 3.4 (95%CI 0-10.7) cases of AMI; 9,789 (95%CI 6,895-11,962) cases of annoyance; 5,084 (95%CI 1,894-10,509) cases of sleep disturbances. CONCLUSIONS: a significant impact of airport noise on the health of residents nearby six Italian airports was estimated. Epidemiological evaluation and noise mitigation measures should be introduced to protect the health of residents. PMID- 25115480 TI - [Vaping: a new strategy to prevent smoking-related diseases?]. AB - By quitting, smokers of all ages can gain substantial health benefits. No other single effort of public health is able to achieve an advantage comparable to smoking cessation on a large scale. However, conventional approaches to smoking cessation require tobacco users to completely abstain, and many smokers are unable - or have not the willingness - to achieve this goal, and then continue to smoke despite the looming negative consequences for health. But it is possible to consider another option: the reduction of harm caused by tobacco smoking (tobacco harm reduction) through the intake of nicotine from alternative sources safer than tobacco smoke, such as the electronic cigarette (e-cig). It is a promising product for the reduction of harm caused by tobacco smoking. In addition to providing nicotine through the vapour without the typical toxic and carcinogenic substances derived from combustion, the e-cig is also a good substitute for the rituals associated with the behaviour of the smoker. In this article, the author suggests that the wide dissemination of vaping behaviour can become a successful strategy to reduce smoking and preventing smoking-related diseases, advancing on how to succeed with this matter. PMID- 25115481 TI - [Codes, guidelines and guidance of ethics of research: the issue of quality]. AB - After an overview of the evolution of ethics laws for medical activities, we suggest a possible classification of documents regarding the ethical conduct of scientific research with human beings. The authors outline the necessity to define formal criteria for the development and the implementation of ethics standards. PMID- 25115483 TI - [In Italy, prevalence of smokers and manufactured cigarettes sales are decreasing, but social differences and sales of fine-cut tobacco are increasing]. PMID- 25115482 TI - [In 2014 cancer registration covers more than half of the Italian population]. PMID- 25115484 TI - Salt-induced self-assembly of bacteria on nanowire arrays. AB - Studying bacteria-nanostructure interactions is crucial to gaining controllable interfacing of biotic and abiotic components in advanced biotechnologies. For bioelectrochemical systems, tunable cell-electrode architectures offer a path toward improving performance and discovering emergent properties. As such, Sporomusa ovata cells cultured on vertical silicon nanowire arrays formed filamentous cells and aligned parallel to the nanowires when grown in increasing ionic concentrations. Here, we propose a model describing the kinetic and the thermodynamic driving forces of bacteria-nanowire interactions. PMID- 25115485 TI - Protection of Wistar-Furth rats against postischaemic acute renal injury: role for nitric oxide and thromboxane? AB - The Wistar-Furth (WF) rat strain is usually used in models of full major histocompatibility complex-mismatched kidney transplantation. Because these rats have been demonstrated to be resistant to several models of chronic kidney disease, the aim of the present study was to investigate their potential resistance to renal ischaemia-reperfusion (I/R) injury compared with another strain, namely Wistar-Hanover (WH) rats. Anaesthetized male WH and WF rats were submitted to I/R by occlusion of the left renal artery and contralateral nephrectomy. Urine, blood and tissue samples were collected at different time points after I/R to evaluate renal function, inflammation and tubular injury, along with determination of nitric oxide synthase (NOS) expression and thromboxane A2 (TxA2 ) production. Post-ischaemic renal function was better preserved in WF than WH rats, as evidenced by reduced levels of creatininaemia, urinary neutrophil gelatinase-associated lipocalin excretion and proteinuria. In addition, WF rats had less intrarenal inflammation than WH rats after I/R injury. These observations were associated with maintenance of neuronal NOS expression, along with lower induction of inducible NOS expression in WF versus WH rats. Moreover, WF rats excreted a significantly lower amount of TxB2 . The results indicate that WF rats are more resistant to an I/R injury than WH rats in terms of renal function and inflammation. These observations are associated with differential regulation of intrarenal NOS expression, as well as a reduction in thromboxane production, which could contribute to a better outcome for the postischaemic kidney in WF rats. PMID- 25115486 TI - X-linked adrenoleukodystrophy: pathogenesis and treatment. AB - X-linked adrenoleukodystrophy (X-ALD) is a puzzling inborn error of metabolism with a strikingly heterogeneous clinical spectrum. All patients have mutations in the ABCD1 gene and accumulate very long chain fatty acids in all tissues. Virtually all male X-ALD patients develop adrenocortical insufficiency in childhood and progressive myelopathy and peripheral neuropathy in adulthood. A subset of male patients, however, develops a fatal cerebral demyelinating disease, cerebral adrenoleukodystrophy. Female patients also develop progressive myelopathy and peripheral neuropathy, but generally at a later age than males. They only very rarely develop adrenocortical insufficiency or cerebral adrenoleukodystrophy. This review proposes to simplify the classification of the clinical spectrum of X-ALD and reviews the largely unresolved pathophysiological mechanisms and the current treatment options. PMID- 25115487 TI - Traffic jam in the primitive streak: the role of defective mesoderm migration in birth defects. AB - Gastrulation is the process in which the three germ layers are formed that contribute to the formation of all major tissues in the developing embryo. We here review mouse genetic models in which defective gastrulation leads to mesoderm insufficiencies in the embryo. Depending on severity of the abnormalities, the outcomes range from incompatible with embryonic survival to structural birth defects, such as heart defects, spina bifida, or caudal dysgenesis. The combined evidence from the mutant models supports the notion that these congenital anomalies can originate from perturbations of mesoderm specification, epithelial-mesenchymal transition, and mesodermal cell migration. Knowledge about the molecular pathways involved may help to improve strategies for the prevention of major structural birth defects. PMID- 25115489 TI - A systematic review of evaluated suicide prevention programs targeting indigenous youth. AB - BACKGROUND: Indigenous young people have significantly higher suicide rates than their non-indigenous counterparts. There is a need for culturally appropriate and effective suicide prevention programs for this demographic. AIMS: This review assesses suicide prevention programs that have been evaluated for indigenous youth in Australia, Canada, New Zealand, and the United States. METHOD: The databases MEDLINE and PsycINFO were searched for publications on suicide prevention programs targeting indigenous youth that include reports on evaluations and outcomes. Program content, indigenous involvement, evaluation design, program implementation, and outcomes were assessed for each article. RESULTS: The search yielded 229 articles; 90 abstracts were assessed, and 11 articles describing nine programs were reviewed. Two Australian programs and seven American programs were included. Programs were culturally tailored, flexible, and incorporated multiple-levels of prevention. No randomized controlled trials were found, and many programs employed ad hoc evaluations, poor program description, and no process evaluation. CONCLUSION: Despite culturally appropriate content, the results of the review indicate that more controlled study designs using planned evaluations and valid outcome measures are needed in research on indigenous youth suicide prevention. Such changes may positively influence the future of research on indigenous youth suicide prevention as the outcomes and efficacy will be more reliable. PMID- 25115491 TI - Suicide ideation and attempts and bullying in children and adolescents: psychiatric and general population samples. AB - BACKGROUND: Studies of the relationship between bullying and suicide behavior yield mixed results. AIMS: This is the first study comparing frequencies of suicide behavior in four bullying groups (bully, victim, bully/victim, and neither) in two large psychiatric and community samples of young children and adolescents. METHOD: Maternal ratings of bullying and suicide ideation and attempts were analyzed for 1,291 children with psychiatric disorders and 658 children in the general population 6-18 years old. RESULTS: For both the psychiatric and community samples, suicide ideation and attempt scores for bully/victims were significantly higher than for victims only and for neither bullies nor victims. Differences between victims only and neither victims nor bullies were nonsignificant. Controlling for sadness and conduct problems, suicide behavior did not differ between the four bullying groups. All children with suicide attempts had a comorbid psychiatric disorder, as did all but two children with suicide ideation. CONCLUSION: Although the contribution of bullying per se to suicide behavior independent of sadness and conduct problems is small, bullying has obvious negative psychological consequences that make intervention imperative. Interventions need to focus on the psychopathology associated with being a victim and/or perpetrator of bullying in order to reduce suicide behavior. PMID- 25115490 TI - Assessing suicide attempts and depression among Chinese speakers over the Internet. AB - BACKGROUND: In populations where mental health resources are scarce or unavailable, or where stigma prevents help-seeking, the Internet may be a way to identify and reach at-risk persons using self-report validated screening tools as well as to characterize individuals seeking health information online. AIMS: We examined the feasibility of delivering an Internet-based Chinese-language depression and suicide screener and described its users. METHOD: An Internet based depression and suicide screener was created and advertised primarily through Google AdWords. Participants completed a suicide and depression screening measure and received individualized feedback, which, if necessary, included the suggestion to seek additional mental health resources. RESULTS: In 7 months, 11,631 individuals visited the site; 4,709 provided valid information. Nearly half reported a current major depressive episode (MDE) and 18.3% a recent suicide attempt; however, over 75% reported never having sought help, including 77.7% of those with MDEs and 75.9% of those reporting a suicide attempt. As participants found the site by searching for depression information online, results may not generalize to the entire Chinese-speaking population. CONCLUSION: Online screening can feasibly identify and reach many at-risk Chinese-speaking persons. It may provide resources to those with limited access to services or to those reluctant to seek such services. PMID- 25115488 TI - IglC and PdpA are important for promoting Francisella invasion and intracellular growth in epithelial cells. AB - The highly infectious bacteria, Francisella tularensis, colonize a variety of organs and replicate within both phagocytic as well as non-phagocytic cells, to cause the disease tularemia. These microbes contain a conserved cluster of important virulence genes referred to as the Francisella Pathogenicity Island (FPI). Two of the most characterized FPI genes, iglC and pdpA, play a central role in bacterial survival and proliferation within phagocytes, but do not influence bacterial internalization. Yet, their involvement in non-phagocytic epithelial cell infections remains unexplored. To examine the functions of IglC and PdpA on bacterial invasion and replication during epithelial cell infections, we infected liver and lung epithelial cells with F. novicida and F. tularensis 'Type B' Live Vaccine Strain (LVS) deletion mutants (DeltaiglC and DeltapdpA) as well as their respective gene complements. We found that deletion of either gene significantly reduced their ability to invade and replicate in epithelial cells. Gene complementation of iglC and pdpA partially rescued bacterial invasion and intracellular growth. Additionally, substantial LAMP1-association with both deletion mutants was observed up to 12 h suggesting that the absence of IglC and PdpA caused deficiencies in their ability to dissociate from LAMP1-positive Francisella Containing Vacuoles (FCVs). This work provides the first evidence that IglC and PdpA are important pathogenic factors for invasion and intracellular growth of Francisella in epithelial cells, and further highlights the discrete mechanisms involved in Francisella infections between phagocytic and non-phagocytic cells. PMID- 25115494 TI - Effect of a contact monitoring system with immediate visual feedback on hand hygiene compliance. AB - BACKGROUND: Hand hygiene compliance is traditionally monitored by visual methods that are open to bias and strictly limited in time and place. Automatic monitoring may be more effective for infection control as well as performance management. AIM: To establish accuracy and acceptability of an automatic contact monitoring system for hand hygiene. METHODS: Monitoring equipment was installed across 55 beds in three wards, and included modified identity badges, bedside furniture, sinks and alcohol gel dispensers. Badges were in near-skin contact (through uniform) and could detect alcohol vapour. All devices were linked by wi fi. A traffic light system on the badge provided immediate feedback to staff and patients on the hand hygiene status of a member of staff on approach to a patient. Compliance was logged automatically. Following a period of immediate feedback, no visual feedback was given for two weeks. Subsequently, feedback was given using red/green lights for 10 days, followed by retrospective feedback to the ward. Hand hygiene was verified independently by an observer. FINDINGS: Hand hygiene compliance increased from 21% of 97 opportunities to 66% of 197 opportunities during active immediate feedback. Compliance decreased when feedback was provided to wards retrospectively. Six staff (26%) avoided wearing a badge, saying that it was too heavy or they were not on the ward all day. Only three of 30 patients stated that they would challenge staff who had not performed hand hygiene. CONCLUSIONS: Automatic contact monitoring with immediate feedback was effective in increasing hand hygiene compliance, but feedback given retrospectively did not prevent a decrease in compliance. PMID- 25115496 TI - Urinoma following Kidney Biopsy: A Case Report. AB - Major complications of a percutaneous kidney biopsy are infrequent but warrant early detection and appropriate treatment. We herein report a patient who developed urinoma following kidney biopsy in the effort to emphasize the paramount importance for practitioners to recognize this complication. Prompt diagnosis and proper management of urinoma following kidney biopsy is prudent as delayed treatment may lead to abscess formation, hydronephrosis, obstructive uropathy and chronic kidney failure. PMID- 25115493 TI - Cross-immunity and age patterns of influenza A(H5N1) infection. AB - The age distribution of influenza A(H5N1) cases reported during 2006-2013 varied substantially between countries. As well as underlying demographic profiles, it is possible that cross-immunity contributed to the age distribution of reported cases: seasonal influenza A(H1N1) and avian influenza A(H5N1) share the same neuraminidase subtype, N1. Using a mechanistic model, we measured the extent to which population age distribution and heterosubtypic cross-immunity could explain the observed age patterns in Cambodia, China, Egypt, Indonesia and Vietnam. Our results support experimental evidence that prior infection with H1N1 confers partial cross-immunity to H5N1, and suggest that more than 50% of spillover events did not lead to reported cases of infection as a result. We also identified age groups that have additional risk factors for influenza A(H5N1) not captured by demography or infection history. PMID- 25115497 TI - Characterization of a double-hit murine model of acute respiratory distress syndrome. AB - The aim of the present study was to characterize a murine model of acute respiratory distress syndrome (ARDS) abiding by the Berlin definition of human ARDS and guidelines for animal models of ARDS. To this end, C57BL/6NCrl mice were challenged with lipopolysaccharide (LPS; 15 mg/kg, i.p.) followed 18 h later by injection of oleic acid (OA; 0.12 mL/kg, i.v.). Controls received saline injection at both time points. Haemodynamics were monitored continuously. Arterial blood gas analyses were performed just before and every 30 min after OA challenge. Ninety minutes after OA challenge, the chest of mice was scanned using micro-computed tomography (CT). Cytokine concentrations were measured in plasma samples. Lungs were harvested 90 min after OA challenge for histology, immunohistochemistry, lung weight measurements and tissue cytokine detection. A histological lung injury score was determined. Eighteen hours after LPS challenge, mice exhibited a severe systemic inflammatory response syndrome. Oxygenation declined significantly after OA injections (Pa o2 /Fi o2 283 +/- 73 and 256 +/- 71 mmHg at 60 and 90 min, respectively; P < 0.001). Bilateral patchy infiltrates were present on the micro-CT scans. Histology revealed parenchymal damage with accumulation of polymorphonuclear neutrophils, intra-alveolar proteinacous debris and few hyaline membranes. The lung wet : dry ratio indicated damage to the alveolar capillary membrane. Cytokine patterns evidenced a severe local and systemic inflammatory state in plasma and lung tissue. In conclusion, the described two-hit model of ARDS shows a pathological picture of ARDS closely mimicking human ARDS according to the Berlin definition and may facilitate interpretation of prospective experimental results. PMID- 25115498 TI - A MAVS/TICAM-1-independent interferon-inducing pathway contributes to regulation of hepatitis B virus replication in the mouse hydrodynamic injection model. AB - Toll-like receptors (TLRs) and cytoplasmic RNA sensors have been reported to be involved in the regulation of hepatitis B virus (HBV) replication, but remain controversial due to the lack of a natural infectious model. Our current study sets out to characterize aspects of the role of the innate immune system in eliminating HBV using hydrodynamic-based injection of HBV replicative plasmid and knockout mice deficient in specific pathways of the innate system. The evidence indicated that viral replication was not affected by MAVS or TICAM-1 knockout, but absence of interferon regulatory factor 3 (IRF-3) and IRF-7 transcription factors, as well as the interferon (IFN) receptor, had an adverse effect on the inhibition of HBV replication, demonstrating the dispensability of MAVS and TICAM 1 pathways in the early innate response against HBV. Myd88(-/-) mice did not have a significant increase in the initial viremia, but substantial viral antigen persisted in the mice sera, a response similar to Rag2(-/-) mice, suggesting that the MyD88-dependent pathway participated in evoking an adaptive immune response against the clearance of intrahepatic HBV. Taken together, we show that the RNA sensing pathways do not participate in the regulation of HBV replication in a mouse model; meanwhile MyD88 is implicated in the HBV clearance. PMID- 25115499 TI - Endoscopic approaches for the diagnosis of autoimmune pancreatitis. AB - Autoimmune pancreatitis (AIP) is characterized by diffuse pancreatic enlargement and irregular narrowing of the main pancreatic duct (MPD). Immunoglobulin (Ig)G4 related sclerosing cholangitis (IgG4-SC) associated with AIP frequently appears as a bile duct stricture. Therefore, it is important to differentiate AIP and IgG4-SC from pancreatic cancer and cholangiocarcinoma or primary sclerosing cholangitis, respectively. Endoscopy plays a central role in the diagnosis of AIP and IgG4-SC because it provides imaging of the MPD and bile duct strictures as well as the ability to obtain tissue samples for histological evaluations. Diffuse irregular narrowing of MPD on endoscopic retrograde cholangiopancreatography (ERCP) is rather specific to AIP, but localized narrowing of the MPD is often difficult to differentiate from MPD stenosis caused by pancreatic cancer. A long stricture (>1/3 the length of the MPD) and lack of upstream dilatation from the stricture (<5 mm) might be key features of AIP on ERCP. Some cholangiographic features, such as segmental strictures, stric tures of the lower bile duct, and long strictures with prestenotic dilatation, are more common in IgG4-SC than in cholangiocarcinoma. Endoscopic ultrasonography (EUS) reveals diffuse hypoechoic pancreatic enlargement, sometimes with hypoechoic inclusions, in patients with AIP. In addition, EUS-elastography and contrast enhanced harmonic EUS have been developed with promising results. The usefulness of EUS-guided fine-needle aspiration has been increasingly recognized for obtaining adequate tissue samples for the histological diagnosis of AIP. Further improvement of endoscopic procedures and devices will contribute to more accurate diagnosis of AIP and IgG4-SC. PMID- 25115500 TI - Vitamin D deficiency in patients with primary immune-mediated peripheral neuropathies. AB - PURPOSE: T cells are important in the immunopathology of immune-mediated peripheral neuropathies (PNP) and activated vitamin D regulates the immune response through increasing the amount of regulatory T cells. An association between vitamin D deficiency and polyneuropathy has been stipulated; hence we assessed whether patients with primary immune-mediated PNP have low vitamin D [25(OH)D] levels. METHODS: Plasma levels of 25(OH)D were analyzed in 26 patients with primary immune-mediated PNP, 50 healthy matched blood donors and 24 patients with motor neuron disease (MND). INCAT score was assessed in patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy. ALSFRS-R score was applied to MND patients and the modified Rankin (mRankin) scale compared disability among patient groups. RESULTS: Mean 25(OH)D value in PNP patients was 40 +/- 16 nmol/l, compared to 69 +/- 21 nmol/l in healthy blood donors (p<0.001). MND patients had a higher mean 25(OH)D than PNP patients (59 +/ 26 nmol/L; p=0.006) and comparable levels to healthy blood donors (p=0.15). Mean 25(OH)D value was not higher in PNP patients with pre-existing vitamin D3 supplementation of 800 IU/day (N=6; 35 +/- 18 nmol/L) than in unsupplemented PNP patients (42 +/- 16 nmol). INCAT score ranged from 0 to 10 (mean 3.5) and ALSFRS R ranged from 11 to 44 (mean 31). mRankin score was more severe in MND patients (mean 3.5) compared to PNP patients (mean 2.1). CONCLUSIONS: All patients with primary immune-mediated PNP were diagnosed with vitamin D deficiency and they had significantly lower 25(OH)D values than healthy control persons and MND patients. We suggest monitoring of vitamin D status in patients with autoimmune PNP, since immune cells are responsive to the ameliorative effects of vitamin D. PMID- 25115501 TI - Acute neurological worsening after Rituximab treatment in patients with anti-MAG neuropathy. AB - BACKGROUND: Patients with peripheral neuropathy and anti-MAG monoclonal IgM may respond to Rituximab, a humanized monoclonal anti-CD20 antibody. METHODS: We report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM who deteriorated under Rituximab and reviewed seven previously published cases. RESULTS: Worsening was acute and severe, and occurred during the treatment period. All the patients improved after deterioration but at final evaluation only one was improved comparatively to baseline, five were worsened and four were stabilized. Deterioration was not clearly associated with an increase of the anti MAG antibody titer. Two patients received Rituximab prior or after the course which induced worsening without adverse reaction. CONCLUSION: Although rare, acute worsening of the neuropathy can occur after Rituximab. The deterioration is however reversible within some weeks to several months. PMID- 25115502 TI - Are natural killer cells involved in multiple sclerosis etiology? Evidences from NKp46/NCR1 receptor modulation in an observational study. AB - Natural killer (NK) cells are implicated in many autoimmune diseases but their role in multiple sclerosis (MS) remains still unknown. This study was aimed to evaluate the expression levels of a NK cell receptor (NCR1) in patients with diagnosis of MS. Particularly, the study took into account patients undergoing pharmacological therapy with interferon-beta or natalizumab and patients never treated since first-time diagnosed for MS. Expression levels of NCR1 receptor were evaluated in protein extracts of peripheral blood mononuclear cells performing western blot analysis. Our results show that MS patients display higher NCR1 expression levels than healthy controls. Moreover, patients with a first diagnosis of MS display the highest level of NCR1 when compared with patients pharmacologically treated with interferon-beta or natalizumab. Therefore, pharmacologically treated MS patients show a modulated NK cell expression. PMID- 25115503 TI - Sporadic Creutzfeldt-Jakob disease with mesiotemporal hypermetabolism. PMID- 25115505 TI - G tolerance and the vasoconstrictor reserve. AB - PURPOSE: Because leg arterial stiffness is higher in subjects with high G tolerance, we hypothesized that subjects with high G tolerance would have larger capacity for vasoconstriction. METHODS: Sixteen subjects, eight with high and eight with low G tolerance (H and L group, respectively), were exposed to a cold pressor test (CPT) in supine and upright posture. Heart rate (HR), mean arterial pressure (MAP) and cardiac output (CO) were measured, and total peripheral resistance (TPR) and stroke volume (SV) were calculated. RESULTS: In the supine position, CPT increased TPR more in the H group; 31 +/- 18% than in the L group; 11 +/- 7% (p < 0.05). The L group had larger increases in CO than the H group; 17 +/- 16 vs. 3.4 +/- 7% (p = 0.06). In the upright position, the H group had a larger MAP response to CPT than the L group; 26 +/- 14 vs. 14 +/- 7% (p = 0.06). The H group, but not the L group, had significant increases in TPR whereas the L group had significant increases in CO and SV. CONCLUSIONS: In response to CPT, the high G tolerance group elevated MAP by increasing TPR, whereas the low G tolerance group showed a dependency on increased CO. The H group seemed to have a larger vasoconstrictor reserve. The results further suggest that vasoconstrictor reserve capacity could constitute the link between the recent finding that indicates a relationship between G tolerance and arterial distensibility in the legs. PMID- 25115504 TI - Analysis of the quantitative balance between insulin-like growth factor (IGF)-1 ligand, receptor, and binding protein levels to predict cell sensitivity and therapeutic efficacy. AB - BACKGROUND: The insulin-like growth factor (IGF) system impacts cell proliferation and is highly activated in ovarian cancer. While an attractive therapeutic target, the IGF system is complex with two receptors (IGF1R, IGF2R), two ligands (IGF1, IGF2), and at least six high affinity IGF-binding proteins (IGFBPs) that regulate the bioavailability of IGF ligands. We hypothesized that a quantitative balance between these different network components regulated cell response. RESULTS: OVCAR5, an immortalized ovarian cancer cell line, were found to be sensitive to IGF1, with the dose of IGF1 (i.e., the total mass of IGF1 available) a more reliable predictor of cell response than ligand concentration. The applied dose of IGF1 was depleted by both cell-secreted IGFBPs and endocytic trafficking, with IGFBPs sequestering up to 90% of the available ligand. To explore how different variables (i.e., IGF1, IGFBPs, and IGF1R levels) impacted cell response, a mass-action steady-state model was developed. Examination of the model revealed that the level of IGF1-IGF1R complexes per cell was directly proportional to the extent of proliferation induced by IGF1. Model analysis suggested, and experimental results confirmed, that IGFBPs present during IGF1 treatment significantly decreased IGF1-mediated proliferation. We utilized this model to assess the efficacy of IGF1 and IGF1R antibodies against different network compositions and determined that IGF1R antibodies were more globally effective due to the receptor-limited state of the network. CONCLUSIONS: Changes that affect IGF1R occupancy have predictable effects on IGF1-induced proliferation and our model captured these effects. Analysis of this model suggests that IGF1R antibodies will be more effective than IGF1 antibodies, although the difference was minimal in conditions with low levels of IGF1 and IGFBPs. Examining how different components of the IGF system influence cell response will be critical to improve our understanding of the IGF signaling network in ovarian cancer. PMID- 25115506 TI - Assessing neonatal heat balance and physiological strain in newborn infants nursed under radiant warmers in intensive care with fentanyl sedation. AB - PURPOSE: To assess heat balance status of newborn infants nursed under radiant warmers (RWs) during intensive care. METHODS: Heat balance, thermal status and primary indicators of physiological strain were concurrently measured in 14 newborns nursed under RWs for 105 min. Metabolic heat production (M), evaporative heat loss (E), convective (C) and conductive heat flow (K), rectal temperature (T re) and mean skin temperatures (T sk) were measured continuously. The rate of radiant heat required for heat balance (R req) and the rate of radiant heat provided (R prov) were derived. The rate of body heat storage (S) was calculated using a two-compartment model of 'core' (T re) and 'shell' (T sk) temperatures. RESULTS: Mean M, E, C and K were 10.5 +/- 2.7 W, 5.8 +/- 1.1 W, 6.2 +/- 0.8 W and 0.1 +/- 0.1 W, respectively. Mean R prov (1.7 +/- 2.6 W) and R req (1.7 +/- 2.7 W) were similar (p > 0.05). However, while the resultant mean change in body heat content after 105 min was negligible (-0.1 +/- 3.7 kJ), acute time-dependent changes in S were evidenced by a mean positive heat storage component of +6.4 +/- 2.6 kJ and a mean negative heat storage component of -6.5 +/- 3.7 kJ. Accordingly, large fluctuations in both T re and T sk occurred that were actively induced by changes in RW output. Nonetheless, no active physiological responses (heart rate, breathing frequency and mean arterial pressure) to these bouts of heating and cooling were observed. CONCLUSIONS: RWs maintain net heat balance over a prolonged period, but actively induce acute bouts of heat imbalance that cause rapid changes in T re and T sk. Transient bouts of heat storage do not exacerbate physiological strain, but could in the longer term. PMID- 25115508 TI - Late reactivation of occult hepatitis B virus infection in a patient with chronic lymphocytic leukemia after rituximab and fludarabine-based regimen. PMID- 25115507 TI - Combined caffeine and carbohydrate ingestion: effects on nocturnal sleep and exercise performance in athletes. AB - PURPOSE: In athletes, caffeine use is common although its effects on sleep have not been widely studied. This randomised, double-blind, placebo-controlled crossover trial investigated the effects of late-afternoon caffeine and carbohydrate-electrolyte (CEB) co-ingestion on cycling performance and nocturnal sleep. METHODS: Six male cyclists/triathletes (age 27.5 +/- 6.9 years) completed an afternoon training session (TS; cycling 80 min; 65% VO2max) followed by a 5 kJ kg(-1) cycling time trial (TT). Caffeine (split dose 2 * 3 mg kg(-1)) or placebo was administered 1 h prior and 40 min into the TS. A 7.4% CEB (3 ml kg(-1) every 15 min) was administered during the TS, followed 30 min after by a standardised evening meal. Participants retired at their usual bedtime and indices of sleep duration and quality were monitored via polysomnography. DATA: mean +/- SD. RESULTS: All participants performed better in the caffeine TT (caffeine 19.7 +/- 3.3; placebo 20.5 +/- 3.5 min; p = 0.006), while ratings of perceived exertion (caffeine 12.0 +/- 0.6; placebo 12.9 +/- 0.7; p = 0.004) and heart rate (caffeine 175 +/- 6; placebo 167 +/- 11 bpm; p = 0.085) were lower in the caffeine TS. Caffeine intake induced significant disruptions to a number of sleep indices including increased sleep onset latency (caffeine 51.1 +/- 34.7; placebo 10.2 +/- 4.2 min; p = 0.028) and decreased sleep efficiency (caffeine 76.1 +/- 19.6; placebo 91.5 +/- 4.2%; p = 0.028), rapid eye movement sleep (caffeine 62.1 +/- 19.6; placebo 85.8 +/- 24.7 min; p = 0.028) and total sleep time (caffeine 391 +/ 97; placebo 464 +/- 49 min; p = 0.028). CONCLUSIONS: This study supports a performance-enhancing effect of caffeine, although athletes (especially those using caffeine for late-afternoon/evening training and competition) should consider its deleterious effects on sleep. PMID- 25115509 TI - Comparison of different DNA extraction methods from peripheral blood cells: advice from the Fondazione Italiana Linfomi Minimal Residual Disease Network. AB - Genomic DNA extraction is a primary component of genomic research and diagnostic routine analysis. Recently, the importance of this process has been highlighted by the necessity to standardize the diagnostic procedure. In this regard, the Minimal Residual Disease (MRD) Network of the Fondazione Italiana Linfomi (FIL MRD Network) has performed a comparative study of four different commercially available kits for DNA extraction, applying them on a panel of cellular pellets, with the aim of defining possible technical recommendations in order to harmonize and standardize diagnostic procedures in the clinical setting. Overall, all four kits usually allowed the recovery of a significant quantity of high-quality DNA (in most conditions), although specific indications could be addressed for cellular pellets of different sizes. PMID- 25115510 TI - Lack of myeloproliferative neoplasm-associated CALR mutations in acute promyelocytic leukemia. PMID- 25115511 TI - Calreticulin gene mutations in myeloproliferative neoplasms without Janus kinase 2 mutations. AB - Calreticulin, an endoplasmic reticulum protein with multiple functions involving chaperone activity and calcium homeostasis, plays an important role in cellular proliferation and differentiation. Calreticulin dysfunction is known to be associated with different cancers. Very recently, calreticulin mutations have been identified in myeloproliferative neoplasms (MPNs), with a particularly high frequency in MPNs without Janus kinase 2 (JAK2) mutations, which exhibit clinical characteristics different from those with mutant JAK2. Here, we focus on the structure, function and carcinogenicity of calreticulin, as well as its relationship with MPNs not involving JAK2 mutations. PMID- 25115512 TI - PRDM1/BLIMP1: a tumor suppressor gene in B and T cell lymphomas. AB - The gene encoding the human BLIMP1, prdm1, is located on chromosome 6q21, a locus frequently deleted in lymphoid tumors. BLIMP1 is able to silence its target genes in a context-dependent manner through different mechanisms. BLIMP1 is expressed in both B and T cells, in which it plays important functions. In B cells, BLIMP1 acts as the master regulator of plasma cell differentiation, repressed by BCL6 and repressing both BCL6 and PAX5. In T cells, BLIMP1 is a critical factor for most terminal effector cell differentiation in both CD4+ and CD8+ T cells. BLIMP1 is frequently inactivated in a variety of lymphomas, including diffuse large B cell lymphomas, Natural Killer cell lymphoma and anaplastic large T cell lymphoma. In this review, we will summarize the role of BLIMP1 in normal cells, focusing on lymphoid cells, and on its function as tumor suppressor gene in lymphomas. PMID- 25115513 TI - Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute lymphoblastic leukemia in Indian population: an experimental, computational and meta-analysis. AB - Acute lymphoblastic leukemia (ALL) arises due to several genetic alterations in progenitor cells, and methotrexate is frequently used as part of the treatment regimen. Although there is evidence for an effect of 5,10 methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C variations on drug response in ALL, its risk association for ALL is still unresolved. In a case control study of 203 patients with ALL and 246 controls and meta-analysis in the Indian population, we showed an insignificant association of MTHFR C677T and A1298C genotypes with childhood and adult ALL. Comprehensive in silico characterization of non-synonymous single nucleotide polymorphisms (nsSNPs) and SNPs of the 3' untranslated region (UTR) revealed nine nsSNPs as deleterious, and three SNPs in the 3'UTR could possibly alter the binding of miRNAs. The study revealed that several overlooked SNPs may contribute to the risk of ALL susceptibility and further studies of these SNPs with functional characterization in a large sample size are required to understand the significant role of MTHFR in ALL development. PMID- 25115514 TI - Identification of linoleic acid, a main component of the n-hexane fraction from Dryopteris crassirhizoma, as an anti-Streptococcus mutans biofilm agent. AB - Dryopteris crassirhizoma is a semi-evergreen plant. Previous studies have shown the potential of this plant as an agent for the control of cariogenic biofilms. In this study, the main antibacterial components of the plant were identified by correlating gas chromatography-mass spectrometry data with the antibacterial activity of chloroform and n-hexane fractions and then evaluating the activity of the most potent antibacterial component against Streptococcus mutans UA159 biofilms. The most potent antibacterial component was linoleic acid, a main component of the n-hexane fraction. Linoleic acid reduced viability in a dose dependent manner and reduced biofilm accumulation during initial and mature biofilm formation. Furthermore, when the biofilms were briefly treated with linoleic acid (10 min/treatment, a total of six times), the dry weight of the biofilms was significantly diminished. In addition, the anti-biofilm activity of the n-hexane fraction was similar to that of linoleic acid. These results suggest that the n-hexane fraction of D. crassirhizoma and linoleic acid may be useful for controlling cariogenic biofilms. PMID- 25115516 TI - Membrane biofouling characterization: effects of sample preparation procedures on biofilm structure and the microbial community. AB - Ensuring the quality and reproducibility of results from biofilm structure and microbial community analysis is essential to membrane biofouling studies. This study evaluated the impacts of three sample preparation factors (ie number of buffer rinses, storage time at 4 degrees C, and DNA extraction method) on the downstream analysis of nitrifying biofilms grown on ultrafiltration membranes. Both rinse and storage affected biofilm structure, as suggested by their strong correlation with total biovolume, biofilm thickness, roughness and the spatial distribution of EPS. Significant variations in DNA yields and microbial community diversity were also observed among samples treated by different rinses, storage and DNA extraction methods. For the tested biofilms, two rinses, no storage and DNA extraction with both mechanical and chemical cell lysis from attached biofilm were the optimal sample preparation procedures for obtaining accurate information about biofilm structure, EPS distribution and the microbial community. PMID- 25115515 TI - Growth and development of the barnacle Amphibalanus amphitrite: time and spatially resolved structure and chemistry of the base plate. AB - The radial growth and advancement of the adhesive interface to the substratum of many species of acorn barnacles occurs underwater and beneath an opaque, calcified shell. Here, the time-dependent growth processes involving various autofluorescent materials within the interface of live barnacles are imaged for the first time using 3D time-lapse confocal microscopy. Key features of the interface development in the striped barnacle, Amphibalanus (= Balanus) amphitrite were resolved in situ and include advancement of the barnacle/substratum interface, epicuticle membrane development, protein secretion, and calcification. Microscopic and spectroscopic techniques provide ex situ material identification of regions imaged by confocal microscopy. In situ and ex situ analysis of the interface support the hypothesis that barnacle interface development is a complex process coupling sequential, timed secretory events and morphological changes. This results in a multi-layered interface that concomitantly fulfills the roles of strongly adhering to a substratum while permitting continuous molting and radial growth at the periphery. PMID- 25115517 TI - Identification and characterization of microbial biofilm communities associated with corroded oil pipeline surfaces. AB - Microbially influenced corrosion (MIC) has long been implicated in the deterioration of carbon steel in oil and gas pipeline systems. The authors sought to identify and characterize sessile biofilm communities within a high temperature oil production pipeline, and to compare the profiles of the biofilm community with those of the previously analyzed planktonic communities. Eubacterial and archaeal 16S rRNA sequences of DNA recovered from extracted pipeline pieces, termed 'cookies,' revealed the presence of thermophilic sulfidogenic anaerobes, as well as mesophilic aerobes. Electron microscopy and elemental analysis of cookies confirmed the presence of sessile cells and chemical constituents consistent with corrosive biofilms. Mass spectrometry of cookie acid washes identified putative hydrocarbon metabolites, while surface profiling revealed pitting and general corrosion damage. The results suggest that in an established closed system, the biofilm taxa are representative of the planktonic eubacterial and archaeal community, and that sampling and monitoring of the planktonic bacterial population can offer insight into biocorrosion activity. Additionally, hydrocarbon biodegradation is likely to sustain these communities. The importance of appropriate sample handling and storage procedures to oilfield MIC diagnostics is highlighted. PMID- 25115518 TI - Fouling in your own nest: vessel noise increases biofouling. AB - Globally billions of dollars are spent each year on attempting to reduce marine biofouling on commercial vessels, largely because it results in higher fuel costs due to increased hydrodynamic drag. Biofouling has been long assumed to be primarily due to the availability of vacant space on the surface of the hull. Here, it is shown that the addition of the noise emitted through a vessel's hull in port increases the settlement and growth of biofouling organisms within four weeks of clean surfaces being placed in the sea. More than twice as many bryozoans, oysters, calcareous tube worms and barnacles settled and established on surfaces with vessel noise compared to those without. Likewise, individuals from three species grew significantly larger in size in the presence of vessel noise. The results demonstrate that vessel noise in port is promoting biofouling on hulls and that underwater sound plays a much wider ecological role in the marine environment than was previously considered possible. PMID- 25115519 TI - Presence and function of a thick mucous layer rich in polysaccharides around Bacillus subtilis spores. AB - This study was designed to establish the presence and function of the mucous layer surrounding spores of Bacillus subtilis. First, an external layer of variable thickness and regularity was often observed on B. subtilis spores. Further analyses were performed on B. subtilis 98/7 spores surrounded by a thick layer. The mechanical removal of the layer did not affect their resistance to heat or their ability to germinate but rendered the spore less hydrophilic, more adherent to stainless steel, and more resistant to cleaning. This layer was mainly composed of 6-deoxyhexoses, ie rhamnose, 3-O-methyl-rhamnose and quinovose, but also of glucosamine and muramic lactam, known also to be a part of the bacterial peptidoglycan. The specific hydrolysis of the peptidoglycan using lysozyme altered the structure of the required mucous layer and affected the physico-chemical properties of the spores. Such an outermost mucous layer has also been seen on spores of B. licheniformis and B. clausii isolated from food environments. PMID- 25115520 TI - The significance of calcium ions on Pseudomonas fluorescens biofilms - a structural and mechanical study. AB - The purpose of this study was to investigate the effects of calcium ions on the structural and mechanical properties of Pseudomonas fluorescens biofilms grown for 48 h. Advanced investigative techniques such as confocal laser scanning microscopy and atomic force spectroscopy were employed to characterize biofilm structure as well as biofilm mechanical properties following growth at different calcium concentrations. The presence of calcium during biofilm development led to higher surface coverage with distinct structural phenotypes in the form of a granular and heterogeneous surface, compared with the smoother and homogeneous biofilm surface in the absence of calcium. The presence of calcium also increased the adhesive nature of the biofilm, while reducing its elastic properties. These results suggest that calcium ions could have a functional role in biofilm development and have practical implications, for example, in analysis of biofouling in membrane-based water-treatment processes such as nanofiltration or reverse osmosis where elevated calcium concentrations may occur at the solid liquid interface. PMID- 25115521 TI - Antifouling properties of zinc oxide nanorod coatings. AB - In laboratory experiments, the antifouling (AF) properties of zinc oxide (ZnO) nanorod coatings were investigated using the marine bacterium Acinetobacter sp. AZ4C, larvae of the bryozoan Bugula neritina and the microalga Tetraselmis sp. ZnO nanorod coatings were fabricated on microscope glass substrata by a simple hydrothermal technique using two different molar concentrations (5 and 10 mM) of zinc precursors. These coatings were tested for 5 h under artificial sunlight (1060 W m(-2) or 530 W m(-2)) and in the dark (no irradiation). In the presence of light, both the ZnO nanorod coatings significantly reduced the density of Acinetobacter sp. AZ4C and Tetraselmis sp. in comparison to the control (microscope glass substratum without a ZnO coating). High mortality and low settlement of B. neritina larvae was observed on ZnO nanorod coatings subjected to light irradiation. In darkness, neither mortality nor enhanced settlement of larvae was observed. Larvae of B. neritina were not affected by Zn(2+) ions. The AF effect of the ZnO nanorod coatings was thus attributed to the reactive oxygen species (ROS) produced by photocatalysis. It was concluded that ZnO nanorod coatings effectively prevented marine micro and macrofouling in static conditions. PMID- 25115522 TI - I am pregnant and want to do better but i can't: focus groups with low-income overweight and obese pregnant women. AB - This study was conducted to identify factors that influenced stress, healthy eating and physical activity among low-income overweight or obese pregnant women. We conducted seven focus groups with 96 low-income overweight and obese pregnant women. Common themes were identified from audio tapes and transcripts. Women said that poor communication affected their relationships with spouses or significant others. They were frustrated or upset with significant others for three key reasons: failure to understand or listen to the pregnant women's pregnancy concerns, refusal to be helpful when asked and being overly concerned with the woman's safety. Most women said that they were emotional and took naps throughout the day after becoming pregnant. Many withdrew from their social interactions. They also faced numerous challenges that made healthy eating more difficult, e.g., craving for unhealthy foods and eating foods for comfort. To eat healthier, some reminded themselves to avoid overeating or stop eating in the car. Women were not physically active because of tiredness, lack of motivation, inadequate social support, or bad weather. Some stayed physically active to prevent excessive pregnancy weight gain and have an easier labor. Women equivocally said weighing themselves to manage weight would add to their stress and make them feel more depressed. When designing interventions to help low-income overweight and obese pregnant women avoid excessive pregnancy weight gain, it is important to include information and practical advice on stress management, emphasizing effective communication skills with significant others and helping them plan effective ways to manage negative feelings. PMID- 25115523 TI - Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase increases the expression of interferon-responsive genes. AB - The 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) pathway is an important metabolic route that is present in almost every organism. However, whether HMGCR affects the expression of interferon (IFN)-responsive genes is unclear. In the present study, expression levels of IFN-responsive genes were monitored by real time polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that expression levels of IFN-responsive genes were significantly increased in HMGCR-downregulated cells and HMGCR inhibitor-treated cells, indicating that inhibition of HMGCR activates the expression of IFN responsive genes. The result in this study will provide new insight into the role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in antiviral research. PMID- 25115524 TI - Congenital microcephaly and chorioretinopathy due to de novo heterozygous KIF11 mutations: five novel mutations and review of the literature. AB - The microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome is a distinct microcephaly syndrome. The hallmark features, microcephaly, chorioretinopathy, and lymphedema are frequently recognized at birth. Another clinical entity, the chorioretinal dysplasia, microcephaly and mental retardation syndrome (CDMMR) is a highly overlapping syndrome characterized by more variable lymphedema. Recently, heterozygous mutations in KIF11, a gene encoding a critical spindle motor protein of the Kinesin family, have been reported in individuals with MLCRD, and in individuals with CDMMR. This finding is suggestive of a single clinically variable spectrum. Here, we report on de novo novel mutations of KIF11 in five individuals with severe microcephaly, marked simplification of the gyral pattern on neuroimaging, bilateral chorioretinopathy, and developmental delay. Three patients had congenital lymphedema, and one had congenital bilateral sensorineural hearing loss. This report, therefore, further expands the clinical and molecular spectrum of KIF11-associated microcephaly. PMID- 25115526 TI - Nontuberculous mycobacterial infection in a clinical presentation of Fitz-Hugh Curtis syndrome: a case report with multigene diagnostic approach. AB - BACKGROUND: Fitz-Hugh-Curtis syndrome (FHCS) is caused by inflammation of perihepatic capsules associated with pelvic inflammatory disease. In recent years, infections with nontuberculous mycobacteria (NTM) have been increasingly occurring in immunocompromised and immunocompetent patients. However, NTM has never been reported in patients with FHCS. We present the first case of a patient with extrapulmonary NTM infection in a clinical presentation of FHCS. CASE PRESENTATION: A 26-year-old Korean woman presented with right upper quadrant and suprapubic pain. She was initially suspected to have FHCS. However, she was refractory to conventional antibiotic therapy. Laparoscopy revealed multiple violin-string adhesions of the parietal peritoneum to the liver and miliary-like nodules on the peritoneal surfaces. Diagnosis of NTM was confirmed by the polymerase chain reaction analysis results of biopsy specimens that showed caseating granulomas with positive acid-fast bacilli. Treatment with anti-NTM medications was initiated, and the patient's symptoms were considerably ameliorated. CONCLUSIONS: An awareness of NTM as potential pathogens, even in previously healthy adults, and efforts to exclude other confounding diseases are important to establish the diagnosis of NTM disease. NTM infection can cause various clinical manifestations, which in the present case, overlapped with the symptoms of perihepatic inflammation seen in FHCS. PMID- 25115527 TI - Response to: "Oral manifestations and blood profile in patients with iron deficiency anemia". PMID- 25115528 TI - Oral manifestations and blood profile in patients with iron deficiency anemia. PMID- 25115529 TI - Mobile phone use and health symptoms in children. AB - BACKGROUND/PURPOSE: To investigate the mobile phone (MP) use for talking in relation to health symptoms among 2042 children aged 11-15 years in Taiwan. METHODS: A nationwide, cross-sectional study, using the computer assisted telephone interview (CATI) technique, was conducted in 2009 to collect information on children's utilization of MPs and the perceived health symptoms reported by their parents. RESULTS: The overall prevalence of MP use in the past month was estimated at 63.2% [95% confidence interval (CI) = 61.1-65.3%]. MP use was associated with a significantly increased adjusted odds ratio (AOR) for headaches and migraine (1.42, 95% CI = 1.12-1.81) and skin itches (1.84, 95% CI = 1.47-2.29). Children who regularly used MPs were also considered to have a health status worse than it was 1 year ago (beta = 0.27, 95% CI = 0.17-0.37). CONCLUSION: Although the cross-sectional design precludes the causal inference for the observed association, our study tended to suggest a need for more cautious use of MPs in children, because children are expected to experience a longer lifetime exposure to radiofrequency electromagnetic fields (RF-EMF) from MPs. PMID- 25115530 TI - A novel anabolic agent: a simvastatin analogue without HMG-CoA reductase inhibitory activity. AB - For the first time, structural information regarding the role of simvastatin in bone anabolism is described, and a bone-specific statin is introduced. Polyaspartate-conjugated simvastatin was synthesized by solid-phase synthesis with the assistance of microwave irradiation. It displays significant bone targeting and bone formation with less toxicity than simvastatin. PMID- 25115531 TI - Epidemiology of varicella zoster virus infection in Canada and the United Kingdom - CORRIGENDUM. PMID- 25115537 TI - Comparison of temporal muscle fascia and cartilage grafts in pediatric tympanoplasties. AB - OBJECTIVE: To compare anatomic and functional outcomes of the different graft materials used in pediatric tympanoplasty. MATERIALS AND METHODS: The patients younger than 18 years of age and who had tympanoplasty between 2010 and 2012 were included in the study. Temporal muscle fascia or cartilage was used as the graft material. The age, gender, the side of the operated ear, the operation technique, pre- and postoperative audiological results, and the status of the graft were noted. An intact graft and an air-bone gap (ABG) <= 20 were regarded as surgical success in the postoperative period. Audiograms obtained before surgery and 1 year after surgery were used for the comparison. RESULTS: Sixty pediatric cases were included in the study. Fascia graft was used as the graft material in 35 of them, and cartilage was used in 25 patients. The graft success rate was 82.9% in the fascia group while it was 92% in the cartilage group. In the fascia group preoperative ABG was 28.2 +/- 10.1 dB, postoperative ABG was 15.1 +/- 10.2dB, and postoperative gain was 13.1 +/- 9.6 dB. In the cartilage group, preoperative ABG was 28.9 +/- 10.2dB, and postoperative ABG was 16.8 +/- 10.3 dB with a postoperative gain of 12.1 +/- 6.8 dB. The differences between the fascia and the cartilage groups were not statistically significant either for hearing gain or graft success rate. CONCLUSION: Cartilage and fascia grafts yield similar results for hearing gain and graft success rate in pediatric tympanoplasty. PMID- 25115538 TI - Reproducibility and repeatability of ganglion cell-inner plexiform layer thickness measurements in healthy subjects. AB - PURPOSE: To assess the reproducibility and repeatability of macular ganglion cell inner plexiform layer (GC-IPL) thickness measurements in healthy subjects. PROCEDURES: In this observational study, 60 healthy eyes were subjected to macular GC-IPL thickness measurements by means of CirrusTM high-definition optical coherence tomography (Cirrus version 6.0; Carl Zeiss Meditec, Dublin, Calif., USA) by two examiners in two sessions. Average, minimum and 6 sectoral GC IPL thicknesses were measured. Inter- and intraobserver reproducibility was tested and analyzed by means of the concordance correlation coefficient (CCC). The repeatability of measurements was assessed by the coefficient of repeatability (CR). RESULTS: Mean age (+/-SD) was 29.63 (+/-5.1) years. The CRs for average GC-IPL thickness were 2.1 and 2.2 um for the first and the second operator, respectively. Inter- and intraobserver CCCs ranged from 0.91 (95% CI: 0.89-0.93) to 0.98 (95% CI: 0.96-0.99) and from 0.92 (95% CI: 0.88-0.94) to 0.98 (95% CI: 0.97-0.99), respectively. CONCLUSIONS: GC-IPL thickness measurements in young healthy subjects showed excellent reproducibility and repeatability, especially for average and sectoral GC-IPL thickness measurements. PMID- 25115539 TI - Bone loss and osteoporosis are associated with conversion from mild cognitive impairment to Alzheimer's disease. AB - OBJECTIVE: The aim of this study was to analyze the relationship between low bone mineral density (BMD) and conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia in a Chinese cohort. METHODS: Men and women (n=946) aged 60-75 underwent a dual X-ray absorptiometry (DXA) study of the lumbar spine and hip and were followed annually for 5 years. Their cognitive and functional status were assessed using the Chinese version of the Mini-Mental State Examination (MMSE) and an assessment of the instrumental activities of daily living (ADL). RESULTS: There was a positive relationship between osteoporosis and a decline in cognition and function (P<0.001) based on MMSE and ADL scores. The subjects with BMD values in the lowest quartile had a 2-fold increased risk of AD conversion compared with the controls. These results suggest that severe BMD loss is associated with an increased risk of AD conversion in both women and men. CONCLUSIONS: Osteoporosis was associated with an increased risk of incident AD dementia. Additionally, low BMD at baseline was associated with an increased risk of AD in both women and men. PMID- 25115540 TI - Metabotropic glutamate receptor 5 in Down's syndrome hippocampus during development: increased expression in astrocytes. AB - Metabotropic glutamate receptor 5 (mGluR5) is highly expressed throughout the forebrain and hippocampus. Several lines of evidence support the role of this receptor in brain development and developmental disorders, as well as in neurodegenerative disorders like Alzheimer's disease (AD). In the present study, the expression pattern of mGluR5 was investigated by immunocytochemistry in the developing hippocampus from patients with Down's syndrome (DS) and in adults with DS and AD. mGluR5 was expressed in developing human hippocampus from the earliest stages tested (9 gestational weeks), with strong expression in the ventricular/subventricular zones. We observed a consistent similar temporal and spatial neuronal pattern of expression in DS hippocampus. However, in DS we detected increased prenatal mGluR5 expression in white matter astrocytes, which persisted postnatally. In addition, in adult DS patients with widespread ADassociated neurodegeneration (DS-AD) increased mGluR5 expression was detected in astrocytes around amyloid plaque. In vitro data confirm the existence of a modulatory crosstalk between amyloid-beta and mGluR5 in human astrocytes. These findings demonstrate a developmental regulation of mGluR5 in human hippocampus and suggest a role for this receptor in astrocytes during early development in DS hippocampus, as well as a potential contribution to the pathogenesis of ADassociated pathology. PMID- 25115542 TI - Fluoxetine improves behavioral performance by suppressing the production of soluble beta-amyloid in APP/PS1 mice. AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder of the central nervous system. Current approaches for AD treatment only ameliorate symptoms. Therapeutic strategies that target the pathological processes of the disease remain elusive. Fluoxetine (FLX) is one of the most widely used antidepressants for the treatment of depression and anxiety associated with AD, however, it is unknown if the drug affects the pathogenesis of the disease. We showed that FLX improved spatial memory, learning and emotional behaviors of APP/PS1 mice, a well characterized model of AD. In the same mice, FLX effectively prevented the protein loss of synaptophysin (SYP) and microtubuleassociated protein 2 (MAP2). FLX was unable to prevent plaque formation, but significantly lowered high levels of soluble beta-amyloid (Abeta) in brain tissue, cerebrospinal fluid (CSF) and blood sera. FLX also effectively inhibited the phosphorylation of amyloid precursor protein (APP) at T668, which may be a possible mechanism of the reduced Abeta production in APP/PS1 mouse after treatment. PMID- 25115541 TI - Severe psychiatric disorders in mid-life and risk of dementia in late- life (age 65-84 years): a population based case-control study. AB - OBJECTIVE: To examine the association of mid-life exposure to several psychiatric disorders with the development of late-life dementia. METHODS: A matched case control study using Western Australian state-wide hospital inpatient, outpatient mental health and emergency records linked to death records. Incident dementia cases (2000-2009) aged 65 to 84 years were sex- and age-matched to an electoral roll control. Records as far back as 1970 were used to assess exposure to medical risk factors before age 65 years. Candidate psychiatric risk factors were required to be present at least 10 years before dementia onset to ensure direction of potential causality. Odds ratios were estimated using conditional logistic regression. RESULTS: 13, 568 dementia cases (median age 78.7 years, 43.4 % male) were matched to a control. Depression, bipolar disorder, schizophrenia, anxiety disorder and alcohol dependence were found to be significant and independent risk factors for late-life dementia after adjusting for diabetes, heart disease, cerebrovascular disease and smoking risk factors. The effect of a history of depression, schizophrenia and alcohol dependency on dementia risk varied with age, being strongest for earlier onset late-life dementia and waning at older ages. CONCLUSION: Severe depression, anxiety disorder, bipolar disorder, schizophrenia and alcoholic dependency disorder treated by specialists in psychiatric facilities in mid-life are important risk factors for late-life dementia. These psychiatric conditions need to be considered in future studies of the risk and prevention of late-life dementia. PMID- 25115543 TI - Intraventricular human immunoglobulin distributes extensively but fails to modify amyloid in a mouse model of amyloid deposition. AB - Intravenous immunoglobulin infusions into Alzheimer patients have been found to provide cognitive benefit over a period of 6 mo in open label studies. One suggestion has been that these preparations contain small amounts of antibodies directed against monomeric and oligomeric Abeta which underlie their effectiveness in patients. To test this hypothesis, we infused Gammagard, a version of intravenous immunoglobulin (IVIG), into the lateral ventricle of amyloid precursor protein (APP) transgenic mice with pre-existing amyloid deposits. Mice were infused over 4 weeks, and tested behaviorally for the last 2 weeks of treatment. Brains were analyzed for histopathology. We found widespread distribution of human-immunoglobulin G (h-IgG) staining in the mouse forebrain, including cerebral cortices and hippocampus. Some cortical neurons appeared to concentrate the h-IgG, but we did not detect evidence of amyloid plaque labeling by h-IgG. The IVIG-treated mice had no change in phenotype compared to saline infused animals with respect to activity, learning and memory, or amyloid deposition. APP mice infused with an anti-Abeta monoclonal antibody did show some reduction in amyloid deposits. These data do not support the argument that anti Abeta antibodies in IVIG preparations are responsible for cognitive benefits seen with these preparations. PMID- 25115544 TI - Intravenous immunoglobulin treatment preserves and protects primary rat hippocampal neurons and primary human brain cultures against oxidative insults. AB - Alzheimer's disease (AD) is characterized by deleterious accumulation of amyloid beta (Abeta) peptide into senile plaque, neurofibrillary tangles formed from hyperphosphorylated tau protein, and loss of cholinergic synapses in the cerebral cortex. The deposition of Abeta-loaded plaques results in microglial activation and subsequent production of reactive oxygen species (ROS), including free radicals. Neurons in aging and AD brains are particularly vulnerable to ROS and other toxic stimuli. Therefore, agents that decrease the vulnerability of neurons against ROS may provide therapeutic values for the treatment or prevention of AD. In the present study, our goal was to test whether intravenous immunoglobulin (IVIG) treatment could preserve as well as protect neurons from oxidative damage. We report that treatment with IVIG protects neuronal viability and synaptic proteins in primary rat hippocampal neurons. Further, we demonstrate the tolerability of IVIG treatment in the primary human fetal mixed brain cultures. Indeed, a high dose (20 mg/ml) of IVIG treatment was well-tolerated by primary human brain cultures that exhibit a normal neuronal phenotype. We also observed a potent neuropreservatory effect of IVIG against ROS-mediated oxidative insults in these human fetal brain cultures. These results indicate that IVIG treatment has great potential to preserve and protect primary human neuronal-enriched cultures and to potentially rescue dying neurons from oxidative insults. Therefore, our findings suggest that IVIG treatment may represent an important therapeutic agent for clinical trials designed to prevent and delay the onset of neurodegeneration as well as AD pathology. PMID- 25115545 TI - Role of complement systems in IVIG mediated attenuation of cognitive deterioration in Alzheimer's disease. AB - Human intravenous immunoglobulin (IVIG) has been indicated as a potential therapy for autoimmune neurological disorders, as well as in many neurodegenerative diseases, with various underlying therapeutic mechanisms such as regulation of T cell trafficking, cytokines, Fc receptor blocking, and interruption of complement activation cascade. In Alzheimer's disease (AD), IVIG presents naturally occurring antibodies against amyloid-beta (Abeta) aggregation, thus IVIG immunotherapy may increase the clearance of Abeta and protect brain function. Recently, we and others reported that besides Abeta clearance, IVIG specifically regulates the levels of complement-derived anaphylatoxins, such as C5a and C3, which play an important role in the regulation of AMPA and NMDA receptor expression in the brain and further upregulate the AMPA-PKA-CREB signaling pathway and synaptic function in AD mouse models. Since down-regulation of complement components has been linked with deficits of cognitive function in age related dementia following the decline of innate immunity during aging, the IVIG immunotherapy could be an attractive novel AD therapeutic through its local regulation of C3, C5a component levels in brain. PMID- 25115546 TI - Intravenous immunoglobulins for Alzheimer's disease. AB - Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with intracerebral accumulation of aggregated amyloid-beta (Abeta) and tau proteins, as well as neuroinflammation. Human intravenous immunoglobulin (IVIG) is a mixture of polyclonal IgG antibodies isolated and pooled from thousands of healthy human donors. The scientific rationale for testing IVIG as a potential AD treatment include its natural anti-Abeta antibody activity, its favorable safety profile and inherent anti-inflammatory/immunomodulatory properties. Over the past decade, several clinical and pre-clinical experimental findings, advanced our knowledge about biological and therapeutic properties of IVIG that are relevant to AD therapy. Anti-amyloid antibodies in IVIG show significantly higher binding avidity for amyloid oligomers and fibrils than for Abeta monomers. In a double transgenic murine model of AD, intracerebral injection of IVIG causes suppression of Abeta fibril pathology whereas long term peripheral IVIG treatments causes elevation of total brain Abeta levels with no measurable impact on Abeta deposits or tendency for inducing cerebral microhemmorhage. Furthermore, chronic IVIG treatment suppressed neuroinflammation and fostered adult hippocampal neurogenesis. In clinical studies with AD patients, IVIG showed an acceptable safety profile and has not been reported to increase the incidence of amyloid related imaging abnormalities. Preliminary studies on small number of patients reported clinical benefits in mild to moderate stage AD patients. However, double blind, placebo controlled studies later did not replicate those initial findings. Interestingly though, in APOE4 carriers and in moderate disease stage subgroups, positive cognitive signals were reported. Nevertheless, both clinical and experimental (mouse) studies show that antibodies in IVIG can accumulate in CNS and its biological activities include neutralization of Abeta oligomers, suppression of neuroinflammation and immunomodulation. Identifying mediators of IVIG's effects at the cellular and molecular level is warranted. In light of its favourable safety profile and aforementioned biological properties, IVIG is still an enigmatic experimental candidate with enormous potential for being an AD therapeutic. PMID- 25115548 TI - Pyloric gland adenoma observed by magnifying endoscopy with narrow-band imaging. PMID- 25115547 TI - Homocysteine and nitrite levels are modulated by MTHFR 677C>T polymorphism in obese women treated with simvastatin. AB - Higher homocysteine (Hcy) levels are associated with cardiovascular risk. The aim of the present study was to evaluate the effect of simvastatin treatment on circulating Hcy levels in obese women without hypertension, diabetes or dyslipidaemia; and to determine whether the 677C>T polymorphism located in methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) gene modulates the effects of this treatment on Hcy and nitrite (as a biomarker of nitric oxide (NO) bioavailability). Twenty-five obese women (body mass index >= 30 kg/m(2) ) who had received 20 mg/day simvastatin for 6 weeks were enrolled in the study. Venous blood samples were collected to measure plasma biomarkers and gene polymorphisms. Simvastatin treatment significantly reduced total cholesterol, low-density lipoprotein-cholesterol, thiobarbituric acid-reactive substances, high sensitivity C-reactive protein and Hcy, whereas nitrite levels were increased. The reduction in Hcy levels in carriers of the T allele was -20.3% compared with 9.4% in patients with the CC genotype. Importantly, before treatment, nitrite levels were significantly higher in patients with the CC genotype compared with T allele carriers, whereas after treatment these levels were similar between groups. Our findings demonstrate that obese women without comorbidities and carrying the T variant of the 677C>T polymorphism of MTHFR exhibit benefits with simvastatin treatment, mainly in terms of increased NO levels. PMID- 25115549 TI - Do the genes of the innate immune response contribute to neuroprotection in Drosophila? AB - A profound debate exists on the relationship between neurodegeneration and the innate immune response in humans. Although it is clear that such a relation exists, the causes and consequences of this complex association remain to be determined in detail. Drosophila is being used to investigate the mechanisms involved in neurodegeneration, and all genomic studies on this issue have generated gene catalogues enriched in genes of the innate immune response. We review the data reported in these publications and propose that the abundance of immune genes in studies of neurodegeneration reflects at least two phenomena: (i) some proteins have functions in both immune and nervous systems, and (ii) immune genes might also be of neuroprotective value in Drosophila. This review opens this debate in Drosophila, which could thus be used as an instrumental model to elucidate this question. PMID- 25115550 TI - (18)F-fluorodeoxyglucose uptake in brown adipose tissue during insulin-induced hypoglycemia and mild cold exposure in non-diabetic adults. AB - OBJECTIVE: Hypoglycemia is associated with increased heat production and, despite of this, hypothermia. Heat production is likely to be mediated by sympathetic innervation. Brown adipose tissue is activated by cold exposure and stimulated by the sympathetic nervous system. We therefore examined the effect of hypoglycemia on uptake of the labeled glucose analogue (18)F-fluorodeoxyglucose in brown adipose tissue using positron emission tomography and computer tomography. METHODS: In nine healthy adults (18)F-fluorodeoxyglucose uptake as measure of brown adipose tissue activity was assessed in a cold environment (17 degrees C) during euglycemia (blood glucose 4.5 mmol/L) and hypoglycemia (2.5 mmol/L) using a hyperinsulinemic glucose clamp. RESULTS: Brown adipose tissue activity was observed in all participants. No difference was observed in the median (range) maximal standardized uptake values of (18)F-fluorodeoxyglucose in brown adipose tissue between euglycemia and hypoglycemia: 4.2 (1.0-7.7) versus 3.1 (2.2-12.5) g/mL (p=0.7). Similarly there were no differences in mean standardized (18)F fluorodeoxyglucose uptake values or total brown adipose tissue volume between euglycemia and hypoglycemia. Body temperature dropped by 0.6 degrees C from baseline during the hypoglycemic condition and remained unchanged during the euglycemic condition. There was no correlation between the maximal standardized uptake values of (18)F-fluorodeoxyglucose in brown adipose tissue and levels of counterregulatory hormones. CONCLUSIONS: This study shows that there is a similar amount of (18)F-fluorodeoxyglucose uptake in brown adipose tissue during hypoglycemia when compared to euglycemia, which makes a role for systemic catecholamines in brown adipose tissue activation and a role for brown adipose tissue thermogenesis in hypoglycemia associated hypothermia unlikely. Future studies in humans should determine whether hypoglycemia indeed increases energy expenditure, and if so which alternative source can explain this increase. PMID- 25115551 TI - [Studies on markers of exposure and early effect in areas with arsenic pollution: methods and results of the project SEpiAs. Epidemiological studies on population exposed to low-to-moderate arsenic concentration in drinking water]. AB - Arsenic and its inorganic compounds are classified as human carcinogens. Several epidemiological studies conducted in areas of the world characterized by high arsenic concentration in drinking water, even up to 3,000 MUg/l, report associations between arsenic exposure and skin, bladder, lung, liver and kidney cancer as well as cardiovascular diseases, diabetes and reproductive and developmental effects. Since general population is not exposed to these high arsenic concentrations in the last years attention focused on adverse health effects that low-to-moderate arsenic concentrations (0-150 MUg/l) in drinking water could induce. The World Health Organization recommends a maximum limit of 10 MUg/l for arsenic in drinking water. Almost all epidemiological studies conducted on populations exposed to low-to-moderate arsenic concentrations in drinking water are limited due to problems arising from both individual exposure assessment and low subjects number. The aim of the present review is to collect literature-based evidences regarding adverse health effects associated with exposure to low-to-moderate arsenic concentrations in drinking water (10-150 MUg/l) in order to obtain a comprehensive picture of the health outcomes that such exposure can have on general population. PMID- 25115553 TI - Circulating Endothelial Cells and Platelet Microparticles in Mitral Valve Disease With and Without Atrial Fibrillation. AB - Hypercoagulability in mitral valve disease (MVD), a cause of atrial fibrillation (AF) and stroke, is potentially due to endothelial damage/dysfunction (marked by circulating endothelial cells [CECs]), platelet activation (soluble P-selectin [sPsel], platelet microparticles [PMPs], and soluble CD40 [sCD40]), and oxidized low-density lipoprotein (oxLDL) cholesterol. We measured these variables in 24 patients with MVD as well as in 21 with MVD + AF and compared them with 20 healthy controls (HCs). The CECs and PMPs were measured by flow cytometry; sPsel, oxLDL, and CD40 by enzyme-linked immunosorbent assay. Compared with HCs, sPsel and PMPs were equally higher in MVD and MVD + AF; sCD40 and oxLDL were higher in MVD + AF than in HCs and MVD; and CECs were higher in MVD than in the HCs, with further increases in MVD + AF (all P < .001). We conclude that excess platelet activation is present in MVD regardless of AF, and that increased endothelial damage in MVD is greater when compounded by AF. PMID- 25115554 TI - Long-Term Follow-Up of Patients at High Risk for Nephropathy After Contrast Exposure. AB - Contrast medium-induced acute kidney injury (CI-AKI) is associated with morbidity and mortality, but the long-term outcomes of patients who do not develop CI-AKI remain unknown. We assessed clinical end points during long-term follow-up in patients at high risk for nephropathy who did not develop CI-AKI. Patients (n = 135) with impaired renal function (estimated glomerular filtration rate: 30-60 mL/min/1.73 m(2)) were divided into 2 groups according to contrast media (CM) exposure. The primary end point of this study was a composite outcome measure of death or renal failure requiring dialysis. Multivariate analyses identified CM exposure to be independently associated with major adverse long-term outcomes (hazard ratio: 2.3; 95% confidence interval, 1.34-6.52; P = .018). Even when CM exposure does not cause CI-AKI in patients with impaired renal function, in the long term, primary end points occur more frequently in patients exposed to CM than in those with no CM exposure. PMID- 25115552 TI - [Studies on markers of exposure and early effect in areas with arsenic pollution: methods and results of the project SEpiAs. Epidemiological surveillance in areas with environmental pollution by natural or anthropogenic arsenic]. AB - INTRODUCTION: Arsenic and its inorganic compounds are classified as carcinogenic to humans. Exposures to inorganic arsenic (iAs) in drinking water are associated with both carcinogenic and non-carcinogenic effects. The risk assessment of exposures to low-moderate levels of environmental arsenic (As) is a challenging objective for research and public health. The SEpiAs study, funded by the Italian Ministry of Health (CCM), was carried out in four areas with arsenic pollution prevalently of natural origin, Amiata and Viterbo areas, or of industrial origin, Taranto and Gela. MATERIALS AND METHODS: 271 subjects (132 men) aged 20-44, were randomly sampled stratifying by area, gender and age classes. Individual data on residential history, socio-economic status, environmental and occupational exposures, lifestyle and dietary habits, were collected through interviews using questionnaire. In urine samples of recruited subjects, the concentration of inorganic arsenic (iAs) and methylated species (MMA, DMA) was measured using inductively coupled mass spectrometer (DRCICP- MS), after chromatographic separation (HPLC). Molecular biomarkers and biomarkers of DNA damage, as well as markers of cardiovascular risk were measured The distributions of iAs and iAs+MMA+DMA were described by area and gender, geometric mean (GM), percentiles and standard deviation (SD). The associations between As species and variables collected by questionnaire were evaluated by multiple regression analysis. RESULTS: Results showed a high variability of As species within and among areas. Gela and Taranto samples showed higher iAs concentration compared to Viterbo and Amiata. Subjects with iAs>1,5 MUg/L or iAs+MMA+DMA>15 MUg/L (thresholds suggested by the Italian Society of Reference Values), are 137 (50,6%) and 68 (25,1%), respectively. A positive association between iAs and use of drinking water emerged in the Viterbo sample, between iAs and occupational exposure in the Gela and Taranto samples. Fish consumption was associated with higher iAs concentration in the whole sample, and particularly in men of the Gela sample. Similar results were observed for iAs+MMA+DMA. Subjects with iAs or iAs+MMA+DMA values higher than the 95th percentile were 15 (6Taranto, 5 Gela, 3Viterbo, 1 Amiata). The relationships between iAs and organic species (methylation efficiency ratios) were different between sex in the four areas. The relevance of polymorphisms AS3MT Met287Thr, GST-T1, GST-M1, OGG1 was confirmed. The analysis of carotid intima-media-thickness showed normal values, but higher among man of Viterbo, Taranto and Gela areas. CONCLUSIONS: Results are informative of exposure to inorganic and organic As in large or at least non-negligible quotas of the samples. The SEpiAs results suggest a further deepening on routes of exposure to arsenic species, and support the recommendation to implement primary prevention measures to reduce population exposure. PMID- 25115555 TI - Reduced Protein C Activity Might be Associated With Progression of Peripheral Arterial Disease. AB - We evaluated the effect of reduced activities of protein C (PC) and protein S (PS) on the progression of peripheral arterial disease (PAD). We measured PC and PS activities in 106 patients with PAD and 44 patients with abdominal aortic aneurysm (AAA) in the same period. The incidences of PC deficiency in PAD and AAA were 4.7% and 4.5%, respectively, and those of PS were 14.1% and 11.4%, respectively; these incidences were much higher than those in the normal population. The PC and PS activities were significantly lower in patients having critical limb ischemia (CLI) than in patients with intermittent claudication. In particular, lower PC activity and female gender were determinant factors of CLI in multivariate logistic regression analysis. We suggest that PC deficiency is an independent predictor for the progression of CLI. PMID- 25115558 TI - Structural properties of iron-phosphate glasses: spectroscopic studies and ab initio simulations. AB - Vitrification is the most effective method for the immobilization of hazardous waste by incorporating toxic elements into a glass structure. Iron phosphate glasses are presently being considered as matrices for the storage of radioactive waste, even of those which cannot be vitrified using conventional borosilicate waste glass. In this study, a structural model of 60P2O5-40Fe2O3 glass is proposed. The model is based on the crystal structure of FePO4 which is composed of [FeO4][PO4] tetrahedral rings. The rings are optimized using the DFT method and the obtained theoretical FTIR and Raman spectra are being compared with their experimental counterparts. Moreover, the proposed model is in very good agreement with X-ray absorption fine structure spectroscopy (XANES/EXAFS) and Mossbauer spectroscopy measurements. According to the calculations the Fe(3+) is in tetrahedral and five-fold coordination. The maximal predicted load of waste constituents into the glass without rebuilding of the structure is 30 mol%. Below this content, waste constituents balance the charge of [FeO4](-) tetrahedra which leads to their strong bonding to the glass resulting in an increase of the chemical durability, transformation and melting temperatures and density. PMID- 25115556 TI - Mast cells in a murine lung ischemia-reperfusion model of primary graft dysfunction. AB - Primary graft dysfunction (PGD), as characterized by pulmonary infiltrates and high oxygen requirements shortly after reperfusion, is the major cause of early morbidity and mortality after lung transplantation. Donor, recipient and allograft-handling factors are thought to contribute, although new insights regarding pathogenesis are needed to guide approaches to prevention and therapy. Mast cells have been implicated in ischemic tissue injury in other model systems and in allograft rejection, leading to the hypothesis that mast cell degranulation contributes to lung injury following reperfusion injury.We tested this hypothesis in a mouse model of PGD involving reversible disruption of blood flow to one lung. Metrics of injury included albumin permeability, plasma extravasation, lung histopathology, and mast cell degranulation. Responses were assessed in wild-type (Kit+/+) and mast cell-deficient (KitW-sh/W-sh) mice. Because mouse lungs have few mast cells compared with human lungs, we also tested responses in mice with lung mastocytosis generated by injecting bone marrow derived cultured mast cells (BMCMC).We found that ischemic lung responses of mast cell-deficient KitW-sh/W-sh mice did not differ from those of Kit+/+ mice, even after priming for injury using LPS. Degranulated mast cells were more abundant in ischemic than in non-ischemic BMCMC-injected KitW-sh/W-sh lungs. However, lung injury in BMCMC-injected KitW-sh/W-sh and Kit+/+ mice did not differ in globally mast cell-deficient, uninjected KitW-sh/W-sh mice or in wild-type Kit+/+ mice relatively deficient in lung mast cells.These findings predict that mast cells, although activated in lungs injured by ischemia and reperfusion, are not necessary for the development of PGD. PMID- 25115557 TI - Acute respiratory failure in critically ill patients with interstitial lung disease. AB - BACKGROUND: Patients with chronic known or unknown interstitial lung disease (ILD) may present with severe respiratory flares that require intensive management. Outcome data in these patients are scarce. PATIENTS AND METHODS: Clinical and radiological features were collected in 83 patients with ILD associated acute respiratory failure (ARF). Determinants of hospital mortality and response to corticosteroid therapy were identified by logistic regression. RESULTS: Hospital and 1-year mortality rates were 41% and 54% respectively. Pulmonary hypertension, computed tomography (CT) fibrosis and acute kidney injury were independently associated with mortality (odds ratio (OR) 4.55; 95% confidence interval (95%CI) (1.20-17.33); OR, 7.68; (1.78-33.22) and OR 10.60; (2.25-49.97) respectively). Response to steroids was higher in patients with shorter time from hospital admission to corticosteroid therapy. Patients with fibrosis on CT had lower response to steroids (OR, 0.03; (0.005-0.21)). In mechanically ventilated patients, overdistension induced by high PEEP settings was associated with CT fibrosis and hospital mortality. CONCLUSION: Mortality is high in ILD-associated ARF. CT and echocardiography are valuable prognostic tools. Prompt corticosteroid therapy may improve survival. PMID- 25115559 TI - Cotyledonary somatic embryos of Pinus pinaster Ait. most closely resemble fresh, maturing cotyledonary zygotic embryos: biological, carbohydrate and proteomic analyses. AB - Cotyledonary somatic embryos (SEs) of maritime pine are routinely matured for 12 weeks before being germinated and converted to plantlets. Although regeneration success is highly dependent on SEs quality, the date of harvesting is currently determined mainly on the basis of morphological features. This empirical method does not provide any accurate information about embryo quality with respect to storage compounds (proteins, carbohydrates). We first analyzed SEs matured for 10, 12 and 14 weeks by carrying out biological (dry weight, water content) and biochemical measurements (total protein and carbohydrate contents). No difference could be found between collection dates, suggesting that harvesting SEs after 12 weeks is appropriate. Cotyledonary SEs were then compared to various stages, from fresh to fully desiccated, in the development of cotyledonary zygotic embryos (ZEs). We identified profiles that were similar using hierarchical ascendant cluster analysis (HCA). Fresh and dehydrated ZEs could be distinguished, and SEs clustered with fresh ZEs. Both types of embryo exhibited similar carbohydrate and protein contents and signatures. This high level of similarity (94.5 %) was further supported by proteome profiling. Highly expressed proteins included storage, stress-related, late embryogenesis abundant and energy metabolism proteins. By comparing overexpressed proteins in developing and cotyledonary SEs or ZEs, some (23 proteins) could be identified as candidate biomarkers for the late, cotyledonary stage. This is the first report of useful generic protein markers for monitoring embryo development in maritime pine. Our results also suggest that improvements of SEs quality may be achieved if the current maturation conditions are refined. PMID- 25115561 TI - Overgrowth of Douglas fir (Pseudotsuga menziesii Franco) stumps with regenerative tissue as an example of cell ordering and tissue reorganization. AB - MAIN CONCLUSION: Stump overgrowth may serve as a unique model for studying cellular reorganization and mechanisms responsible for cell polarity changes during the process of vascular tissue differentiation from initially unorganized parenchymatous cells. Cellular ordering and tissue reorganization during the overgrowth process of the transverse surfaces of Douglas fir stumps in forest stand was studied. At the beginning of stump overgrowth, the produced parenchymatous cells form an unorganized tissue. Particular parenchyma cells start arranging into more ordered structures which resemble rays. Application of digital image analysis software based on structure tensor was used. The analysis showed that at this stage of tissue development, cellular elements display a wide range of angular orientation values and attain very low coherency coefficients. The progress of the tissue differentiation process is associated with the formation of local regions with tracheids oriented circularly around the rays. This coincides with an increase in the range of angular orientations and greater values of coherency coefficients. At the most advanced stage of tissue development, with tracheids arranged parallelly in longitudinal strands, the degree of cell ordering is the highest what is manifested by the greatest values attained by coherency coefficients, and the narrow range of angular orientations. It is suggested that the ray-like structures could act as organizing centers in the morphogenetic field responsible for differentiation of the overgrowth tissue. The circular pattern of tracheids around rays in the initial phase of tissue development can be interpreted in terms of local rotation of the morphogenetic field which afterward is transformed into irrotational field. This transformation is noted by the presence of tracheids arranged parallelly in longitudinal strands. The possible involvement of a mechanism controlling cell polarity with respect to auxin transport is discussed. PMID- 25115560 TI - Identification and functional characterization of the distinct plant pectin esterases PAE8 and PAE9 and their deletion mutants. AB - MAIN CONCLUSION: PAE8 and PAE9 have pectin acetylesterase activity and together remove one-third of the cell wall acetate associated with pectin formation in Arabidopsis leaves. In pae8 and pae9 mutants, substantial amounts of acetate accumulate in cell walls. In addition, the inflorescence stem height is decreased. Pectic polysaccharides constitute a significant part of the primary cell walls in dicotyledonous angiosperms. This diverse group of polysaccharides has been implicated in several physiological processes including cell-to-cell adhesion and pathogenesis. Several pectic polysaccharides contain acetyl-moieties directly affecting their physical properties such as gelling capacity, an important trait for the food industry. In order to gain further insight into the biological role of pectin acetylation, a reverse genetics approach was used to investigate the function of genes that are members of the Pectin AcetylEsterase gene family (PAE) in Arabidopsis. Mutations in two members of the PAE family (PAE8 and PAE9) lead to cell walls with an approximately 20 % increase in acetate content. High-molecular-weight fractions enriched in pectic rhamnogalacturonan I (RGI) extracted from the mutants had increased acetate content. In addition, the pae8 mutant displayed increased acetate content also in low-molecular-weight pectic fractions. The pae8/pae9-2 double mutant exhibited an additive effect by increasing wall acetate content by up to 37 %, suggesting that the two genes are not redundant and act on acetyl-substituents of different pectic domains. The pae8 and pae8/pae9-2 mutants exhibit reduced inflorescence growth underscoring the role of pectic acetylation in plant development. When heterologously expressed and purified, both gene products were shown to release acetate from the corresponding mutant pectic fractions in vitro. PAEs play a significant role in modulating the acetylation state of pectic polymers in the wall, highlighting the importance of apoplastic metabolism for the plant cell and plant growth. PMID- 25115562 TI - First laccase in green algae: purification and characterization of an extracellular phenol oxidase from Tetracystis aeria. AB - MAIN CONCLUSION: A green algal phenol oxidase was firstly purified, confirmed to be a laccase, and a hetero-oligomeric quaternary structure is suggested. The operation of a laccase-mediator system is firstly described in algae. Laccases (EC 1.10.3.2) catalyze the oxidation of a multitude of aromatic substrates. They are well known in higher plants and fungi, while their presence in green algae appears uncertain. Extracellular laccase-like enzyme activity has previously been described in culture supernatants of the green soil alga Tetracystis aeria [Otto et al. in Arch Microbiol 192:759-768, (2010)]. As reported herein, the T. aeria enzyme was purified 120-fold by employing a combination of anion exchange and size exclusion chromatography. The purified enzyme was confirmed to be a laccase according to its substrate specificity. It oxidizes 2,2'-azino-bis(3 ethylbenzothiazoline-6-sulfonic acid) (ABTS), syringaldazine, and 2,6 dimethoxyphenol (pH optima of pH <= 2.5, 7.0, and 6.5; K m values of 28.8, 40.5, and 1,830 uM; respectively), but not L-tyrosine or Fe(2+). ABTS is by far the most efficient substrate. Two polypeptides, A (~110 kDa) and B (71 kDa), were co purified by the applied procedure, both being highly N-glycosylated (>=~53 and >= 27 %, respectively). As suggested by various gel electrophoretic analyses, the native enzyme (apparent molecular mass of ~220 kDa) most probably is a hetero oligomer with the composition AB 2 , wherein A is the catalytic subunit and B forms a disulfide-linked homo-dimer B2. The decolorization of anthraquinone (Acid Blue 62 and Remazol Brilliant Blue R) and diazo dyes (Reactive Black 5) was studied in the presence of redox-mediating compounds (ABTS and syringaldehyde), demonstrating the operation of the laccase-mediator system in algae for the first time. Thus, laccases from green algae may participate in the biotransformation of a wide spectrum of natural and xenobiotic compounds. PMID- 25115563 TI - Researcher Perspectives on Conflicts of Interest: A Qualitative Analysis of Views from Academia. AB - The increasing interconnectedness of academic research and external industry has left research vulnerable to conflicts of interest. These conflicts have the potential to undermine the integrity of scientific research as well as to threaten public trust in scientific findings. The present effort sought to identify themes in the perspectives of faculty researchers regarding conflicts of interest. Think-aloud interview responses were qualitatively analyzed in an effort to provide insights with regard to appropriate ways to address the threat of conflicts of interest in research. Themes in participant responses included disclosure of conflicts of interest, self-removal from situations where conflict exists, accommodation of conflict, denial of the existence of conflict, and recognition of complexity of situations involving conflicts of interest. Moral disengagement operations are suggested to explain the appearance of each identified theme. In addition, suggestions for best practices regarding addressing conflicts of interest given these themes in faculty perspectives are provided. PMID- 25115564 TI - Technical note: a multi-dimensional description of knee laxity using radial basis functions. AB - The net laxity of the knee is a product of individual ligament structures that provide constraint for multiple degrees of freedom (DOF). Clinical laxity assessments are commonly performed along a single axis of motion, and lack analyses of primary and coupled motions in terms of translations and rotations of the knee. Radial basis functions (RBFs) allow multiple DOF to be incorporated into a single method that accounts for all DOF equally. To evaluate this method, tibiofemoral kinematics were experimentally collected from a single cadaveric specimen during a manual laxity assessment. A radial basis function (RBF) analysis was used to approximate new points over a uniform grid space. The normalized root mean square errors of the approximated points were below 4% for all DOF. This method provides a unique approach to describing joint laxity that incorporates multiple DOF in a single model. PMID- 25115565 TI - A new challenge: suicide attempt using nicotine fillings for electronic cigarettes. PMID- 25115566 TI - Probing the internal electric field in GaN/AlGaN nanowire heterostructures. AB - We demonstrate the direct analysis of polarization-induced internal electric fields in single GaN/Al0.3Ga0.7N nanodiscs embedded in GaN/AlN nanowire heterostructures. Superposition of an external electric field with different polarity results in compensation or enhancement of the quantum-confined Stark effect in the nanodiscs. By field-dependent analysis of the low temperature photoluminescence energy and intensity, we prove the [0001]-polarity of the nanowires and determine the internal electric field strength to 1.5 MV/cm. PMID- 25115567 TI - High vitamin E content, impact resistant UHMWPE blend without loss of wear resistance. AB - Antioxidant stabilization of radiation cross-linked ultrahigh molecular weight polyethylene (UHMWPE) has been introduced to improve the oxidative stability of total joint implant bearing surfaces. Blending of antioxidants (most commonly vitamin E) with UHMWPE resin powder followed by consolidation and uniform radiation cross-linking is currently available for use in both total hips and total knees. It was previously shown that the fatigue resistance of vitamin E blended and irradiated UHMWPEs could be further improved by spatially manipulating the vitamin E concentration throughout the implant and limiting cross-linking to the surface of the implant where it is necessary for wear resistance. This was possible by designing a low concentration of vitamin E on the surface and higher concentration in the bulk of the implant because cross linking is hindered in UHMWPE as a function of increasing vitamin E concentration. In this study, we hypothesized that such a surface cross-linked UHMWPE with low wear rate and high fatigue strength could be obtained by limiting the penetration of radiation into UHMWPE with uniform vitamin E concentration. Our hypothesis tested positive; we were able to obtain control of the surface cross-linked region by manipulating the energy of the irradiation, resulting in extremely low wear, and high impact strength. In addition, we discussed alternatives of improving the oxidation resistance of such a material by using additional vitamin E reservoirs. These results are significant because this material may allow increased use of antioxidant-stabilized, cross-linked UHMWPEs in high stress applications and in more active patients. PMID- 25115570 TI - Palladium-catalyzed aerobic oxidative C-H olefination with removable 1,2,3 triazole directing group. AB - Ortho-olefination of arenes was achieved with removable 1,2,3-triazole auxiliary through Pd-catalyzed C-H activation. Excellent yields were received even when molecular O2 (1 atm) was used as the terminal oxidant. Other heterocyclic directing groups, such as pyridine and quinoline, gave poor reactivity under this aerobic oxidative condition, which highlighted the unique reactivity of triazole in promoting directed C-H activation. PMID- 25115568 TI - Breast bud detection: a validation study in the Chilean growth obesity cohort study. AB - BACKGROUND: Early puberty onset has been related to future chronic disease; however breast bud assessment in large scale population studies is difficult because it requires trained personnel. Thus our aim is to assess the validity of self and maternal breast bud detection, considering girl's body mass index (BMI) and maternal education. METHODS: In 2010, 481 girls (mean age = 7.8) from the Growth and Obesity Chilean Cohort Study were evaluated by a nutritionist trained in breast bud detection. In addition, the girl(n = 481) and her mother(n = 341) classified the girl's breast development after viewing photographs of Tanner stages. Concordance between diagnostics was estimated (kappa, Spearman correlation) considering girls' BMI and mother's educational level. RESULTS: 14% of the girls presented breast buds and 43% had excess weight (BMI z-score > 1, World Health Organization 2007). Self-assessment showed low concordance with the evaluator (K < 0.1) and girls with excess weight over-diagnosed more than girls of normal weight (44% vs. 24%, p-value < 0.05). Instead, mothers showed good concordance with the evaluator (K = 0.7, 95% confidence interval (CI) = 0.6-0.9), even in overweight girls and/or in mothers with low education (K = 0.7, 95% CI = 0.6-0.8). CONCLUSIONS: Mothers were able to adequately evaluate the appearance of breast bud despite low educational level and girls' excess weight. Mother could be a useful resource for defining puberty onset in epidemiological studies, particularly developing countries. PMID- 25115571 TI - Systemic administration of 2-hydroxypropyl-beta-cyclodextrin to symptomatic Npc1 deficient mice slows cholesterol sequestration in the major organs and improves liver function. AB - In Niemann-Pick type C (NPC) disease, loss-of-function mutations in either NPC1 or NPC2 result in progressive accumulation of unesterified cholesterol (UC) and glycosphingolipids in all organs, leading to neurodegeneration, pulmonary dysfunction and sometimes liver failure. There is no cure for this disorder. Studies using primarily NPC mouse models have shown that systemic administration of 2-hydroxypropyl-beta-cyclodextrin (2HPbetaCD), starting in early neonatal life, diminishes UC accumulation in most organs, slows disease progression and extends lifespan. The key question now is whether delaying the start of 2HPbetaCD treatment until early adulthood, when the amount of entrapped UC throughout the body is markedly elevated, has any of the benefits found when treatment begins at 7 days of age. In the present study, Npc1(-/-) and Npc1(+/+) mice were given saline or 2HPbetaCD subcutaneously at 49, 56, 63 and 70 days of age, with measurements of organ weights, liver function tests and tissue cholesterol levels performed at 77 days. In Npc1(-/-) mice, treatment with 2HPbetaCD from 49 days reduced whole-liver cholesterol content at 77 days from 33.0 +/- 1.0 to 9.1 +/- 0.5 mg/organ. Comparable improvements were seen in other organs, such as the spleen, and in the animal as a whole. There was a transient increase in biliary cholesterol concentration in Npc1(-/-) mice after 2HPbetaCD. Plasma alanine aminotransferase and aspartate aminotransferase activities in 77-day-old 2HPbetaCD-treated Npc1(-/-) mice were reduced compared with saline-treated controls. The lifespan of Npc1(-/-) mice given 2HPbetaCD marginally exceeded that of the saline-treated controls (99 +/- 1.1 vs 94 +/- 1.4 days, respectively; P < 0.05). Thus, 2HPbetaCD is effective in mobilizing entrapped cholesterol in late stage NPC disease leading to improved liver function. PMID- 25115572 TI - Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after block. AB - OBJECTIVE: Kilohertz frequency alternating current (KHFAC) waveforms have been shown to provide peripheral nerve conductivity block in many acute and chronic animal models. KHFAC nerve block could be used to address multiple disorders caused by neural over-activity, including blocking pain and spasticity. However, one drawback of KHFAC block is a transient activation of nerve fibers during the initiation of the nerve block, called the onset response. The objective of this study is to evaluate the feasibility of using charge balanced direct current (CBDC) waveforms to temporarily block motor nerve conductivity distally to the KHFAC electrodes to mitigate the block onset-response. APPROACH: A total of eight animals were used in this study. A set of four animals were used to assess feasibility and reproducibility of a combined KHFAC + CBDC block. A following randomized study, conducted on a second set of four animals, compared the onset response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To quantify the onset, peak forces and the force-time integral were measured during KHFAC block initiation. Nerve conductivity was monitored throughout the study by comparing muscle twitch forces evoked by supra-maximal stimulation proximal and distal to the block electrodes. Each animal of the randomized study received at least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of combined KHFAC + CBDC on nerve viability. MAIN RESULTS: The peak onset force was reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45 N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p < 0.001). The area under the force curve was reduced from 6.8 Ns (range: 3.5-21.9 Ns) to 0.54 Ns (range: 0.18-0.86 Ns) (p < 0.01). No change in nerve conductivity was observed after application of the combined KHFAC + CBDC block relative to KHFAC waveforms. SIGNIFICANCE: The distal application of CBDC can significantly reduce or even completely prevent the KHFAC onset response without a change in nerve conductivity. PMID- 25115575 TI - Endoscopic balloon dilatation for pharyngo-upper esophageal stricture after treatment of head and neck cancer. AB - BACKGROUND AND AIM: Dysphagia caused by pharyngo-upper esophageal stricture is a complication of treatment for head and neck cancer. Endoscopic balloon dilation (EBD) is in widespread use as an effective and safe treatment for stricture in many areas of the gastrointestinal tract. In the present study, we investigated the efficacy and safety of EBD for pharyngo-upper esophageal strictures that developed after treatment for head and neck cancer. METHODS: From January 2010 to December 2013, the medical records and endoscopic findings of 19 consecutive patients with pharyngo-upper esophageal strictures occurring after surgery and/or chemoradiotherapy for head and neck cancer were retrospectively examined. RESULTS: Mean number of EBD sessions per patient was 6.6 (1-30), and mean maximum diameter of dilation was 15.8 (11-20) mm. Technical success was achieved in 16 of 19 (84.2%) patients, and only two major complications (bleeding and pha ryngeal edema) occurred in a total of 125 dilatation sessions (1.6%). Regarding the influence of chemoradiotherapy on the outcome of EBD, patients who had undergone chemoradiotherapy plus surgery experienced significantly more restenosis during the follow-up period compared to those who had undergone surgery alone (50% vs 0%, P < 0.05). CONCLUSIONS: This retrospective analysis demonstrated the efficacy and safety of exclusive EBD for pharyngo-upper esophageal strictures occurring after treatment for head and neck cancer, indicating that the therapeutic application of EBD could be extended to such strictures. Patients who underwent chemoradiotherapy and surgery experienced more restenosis; hence, such patients should be carefully followed up after EBD treatment. PMID- 25115576 TI - Invited commentary on the paper entitled 'methicillin-resistant Staphylococcus aureus infection: an independent risk factor for mortality in patients with poststernotomy mediastinitis'. PMID- 25115577 TI - Prevalence of musculoskeletal pain in a sample of migrant workers in the manufacturing industry in Malaysia. PMID- 25115580 TI - The brief cognitive assessment tool (BCAT): cross-validation in a community dwelling older adult sample. AB - ABSTRACT Background: Cognitive impairment is underrecognized and misdiagnosed among community-dwelling older adults. At present, there is no consensus about which cognitive screening tool represents the "gold standard." However, one tool that shows promise is the Brief Cognitive Assessment Tool (BCAT), which was originally validated in an assisted living sample and contains a multi-level memory component (e.g. word lists and story recall items) and complex executive functions features (e.g. judgment, set-shifting, and problem-solving). Methods: The present study cross-validated the BCAT in a sample of 75 community-dwelling older adults. Participants completed a short battery of several individually administered cognitive tests, including the BCAT and the Montreal Cognitive Assessment (MoCA). Using a very conservative MoCA cut score of <26, the base rate of cognitive impairment in this sample was 35%. Results: Adequate internal consistency and strong evidence of construct validity were found. A receiver operating characteristic (ROC) curve was calculated from sensitivity and 1 specificity values for the classification of cognitively impaired versus cognitively unimpaired. The area under the ROC curve (AUC) for the BCAT was .90, p < 0.001, 95% CI [0.83, 0.97]. A BCAT cut-score of 45 (scores below 45 suggesting cognitive impairment) resulted in the best balance between sensitivity (0.81) and specificity (0.80). Conclusions: A BCAT cut-score can be used for identifying persons to be referred to appropriate healthcare professionals for more comprehensive cognitive assessment. In addition, guidelines are provided for clinicians to interpret separate BCAT memory and executive dysfunction component scores. PMID- 25115579 TI - Sustained release of 17beta-estradiol stimulates osteogenic differentiation of adipose tissue-derived mesenchymal stem cells on chitosan-hydroxyapatite scaffolds. AB - The aim of this study was to develop a 17beta-estradiol (E2)-releasing scaffold nanoparticle system in order to promote osteogenic differentiation of rat adipose tissue-derived mesenchymal stem cells (AdMSCs) for bone tissue regeneration. E2 loaded poly(lactide-co-glycolide) (PLGA) nanoparticles with a diameter of ~240 nm were produced via an emulsion-diffusion-evaporation method. Because of its higher encapsulation efficiency (54%), PLGA, which has a 65:35 composition, was chosen for the preparation of nanoparticles. Chitosan-hydroxyapatite (HA) scaffolds in macroporous structures with interconnected pores were prepared by combining microwave irradiation and gas-foaming techniques. PLGA nanoparticles were loaded onto scaffolds in 2 ways: via embedding after scaffold fabrication and during fabrication. While 100% of the loaded E2 was released during 55 days from scaffolds loaded by embedding, a controlled release behavior of E2 was observed over 135 days in scaffolds loaded during manufacture. The results of cell culture studies indicated that the controlled delivery of E2 from PLGA nanoparticles loaded on chitosan-HA scaffolds had a significant effect on the osteogenic differentiation of AdMSCs. PMID- 25115578 TI - Antiadhesive activity of poly-hydroxy butyrate biopolymer from a marine Brevibacterium casei MSI04 against shrimp pathogenic vibrios. AB - BACKGROUND: Vibrio pathogens are causative agents of mid-culture outbreaks, and early mortality syndrome and secondary aetiology of most dreadful viral outbreaks in shrimp aquaculture. Among the pathogenic vibrios group, Vibrio alginolyticus and V. harveyi are considered as the most significant ones in the grow-out ponds of giant black tiger shrimp Penaeus monodon in India. Use of antibiotics was banned in many countries due to the emergence of antibiotic-resistant strains and accumulation of residual antibiotics in harvested shrimp. There is an urgent need to consider the use of alternative antibiotics for the control of vibriosis in shrimp aquaculture. Biofilm formation is a pathogenic and/or establishment mechanism of Vibrio spp. This study aims to develop novel safe antibiofilm and/or antiadhesive process using PHB to contain vibrios outbreaks in shrimp aquaculture. RESULTS: In this study a poly-hydroxy butyrate (PHB) polymer producing bacterium Brevibacterium casei MSI04 was isolated from a marine sponge Dendrilla nigra and production of PHB was optimized under submerged-fermentation (SmF) conditions. The effect of carbon, nitrogen and mineral sources on PHB production and enhanced production of PHB by response surface methods were demonstrated. The maximum PHB accumulation obtained was 6.74 g/L in the optimized media containing 25 g/L starch as carbon source, 96 h of incubation, 35 degrees C and 3% NaCl. The highest antiadhesive activity upto 96% was recorded against V. vulnificus, and V. fischeri, followed by 92% against V. parahaemolyticus and V. alginolyticus and 88% inhibition was recorded against V. harveyi. CONCLUSION: In this study, a thermostable biopolymer was chemically characterized as PHB based on 1HNMR spectra, FT-IR and GC-MS spectra. The NMR spectra revealed that the polymer was an isocratic homopolymer and it also confirmed that the compound was PHB. The antiadhesive activity of PHB was determined in microtitre plate assay and an effective concentration (EC) of PHB (200 MUl containing 0.6 mg PHB) was confirmed by confocal laser scanning microscopic analysis of vibrio biofilm on pre-treated glass and polystyrene surfaces. This is a first report on anti adhesive activity of PHB against prominent vibrio pathogens in shrimp aquaculture. PMID- 25115581 TI - Designing mixed metal halide ammines for ammonia storage using density functional theory and genetic algorithms. AB - Metal halide ammines have great potential as a future, high-density energy carrier in vehicles. So far known materials, e.g. Mg(NH3)6Cl2 and Sr(NH3)8Cl2, are not suitable for automotive, fuel cell applications, because the release of ammonia is a multi-step reaction, requiring too much heat to be supplied, making the total efficiency lower. Here, we apply density functional theory (DFT) calculations to predict new mixed metal halide ammines with improved storage capacities and the ability to release the stored ammonia in one step, at temperatures suitable for system integration with polymer electrolyte membrane fuel cells (PEMFC). We use genetic algorithms (GAs) to search for materials containing up to three different metals (alkaline-earth, 3d and 4d) and two different halides (Cl, Br and I) - almost 27,000 combinations, and have identified novel mixtures, with significantly improved storage capacities. The size of the search space and the chosen fitness function make it possible to verify that the found candidates are the best possible candidates in the search space, proving that the GA implementation is ideal for this kind of computational materials design, requiring calculations on less than two percent of the candidates to identify the global optimum. PMID- 25115582 TI - Histologic analysis of the hernia sac: current practices based on a survey of IPEG members. AB - INTRODUCTION: Inguinal hernia repair is one of the most common operations performed by pediatric surgeons. Although the practice of sending the hernia sac for histologic examination after routine hernia repair is common, the indications and practice patterns for this have not been evaluated. The objective of this survey was to determine practice patterns and indications for histologic analysis of the pediatric inguinal hernia sac. MATERIALS AND METHODS: A 9-question online survey was sent to all members of the International Pediatric Endosurgery Group (IPEG). A Kruskal-Wallis test was used to determine whether practice patterns of sending the hernia sac for histologic evaluation were associated with respondent characteristics. The chi-squared test with Yates's correction was used where appropriate. RESULTS: The survey was completed by 315 IPEG members, for a response rate of 54.4%. Hernia sacs were sent for histologic evaluation always by 23.9%, often by 5.1%, rarely by 17.5%, and never by 53.5%. The respondent characteristics were not associated with whether or not specimens were sent for histology review. Of the 128 who reported sending the inguinal hernia sac, the most common reasons were hospital/state requirements (47.6%), followed by routine practice (25.7%) and concern for missed pathology (24.2%). CONCLUSIONS: The majority of IPEG respondents report never sending the inguinal hernia sac for histologic analysis. Of those that do, most are influenced by hospital/state requirements. The value of sending the hernia sac after routine inguinal hernia repair should be validated if it is to remain an institutional requirement. PMID- 25115583 TI - What are the results using the modified trapdoor procedure to treat chondroblastoma of the femoral head? AB - BACKGROUND: Treatment of chondroblastoma in the femoral head is challenging owing to the particular location and its aggressive nature. There is little published information to guide the surgeon regarding the appropriate approach to treating a chondroblastoma in this location. We developed a modified trapdoor procedure to address this issue. The primary modification is that the window surface of the femoral head is covered by the ligamentum teres rather than cartilage as in the traditional procedure. QUESTIONS/PURPOSES: We assessed (1) the clinical presentation of chondroblastoma of the femoral head and treatment results with the modified trapdoor procedure in terms of (2) the frequency of local recurrence, (3) complications, and (4) functional outcomes using the Musculoskeletal Tumor Society (MSTS) score. METHODS: Between 1999 and 2010, we treated 14 patients for chondroblastoma of the femoral head. All patients received the modified trapdoor procedure. Of those, 13 were available for followup at a minimum of 36 months (mean, 66 months; range, 36-117 months) and one patient was lost to followup. There were nine males and four females, with a mean age of 18 years (range, 9-29 years). Clinical features were ascertained by chart and radiographic review, and recurrence, complications, and functional outcomes (MSTS score) were recorded from chart review. Patterns of bone destruction were evaluated using the Lodwick classification, which ranges from IA (geographic appearance with sclerotic rim) to III (permeative appearance). RESULTS: The symptoms at diagnosis were pain in nine patients and discomfort in four. The mean duration of symptom was 11 months (range, 1-36 months). The physis was open in two patients, closing in one, and closed in 10. The patterns of bone destruction were evaluated as Lodwick Class IA in six patients, Lodwick Class IB in five, and Lodwick Class IC in two. At latest followup, no local recurrence was observed. Two patients had postoperative complications. One had avascular necrosis of the femoral head and was treated with prosthesis replacement. The other had asymptomatic heterotopic ossification in the surgical field. The mean MSTS score was 29.6 (range, 28-30). CONCLUSIONS: Based on this small series, we believe our modified trapdoor procedure is a safe, effective means of treating a chondroblastoma in the femoral head, but additional clinical evaluation with more patients is necessary to confirm our findings. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence. PMID- 25115584 TI - How does ulnar shortening osteotomy influence morphologic changes in the triangular fibrocartilage complex? AB - BACKGROUND: Ulnar shortening osteotomy often is indicated for treatment of injuries to the triangular fibrocartilage complex (TFCC). However, the effect of ulnar shortening osteotomy on the changes in shape of the TFCC is unclear. In our study, quantitative evaluations were performed using MRI to clarify the effect of ulnar shortening on triangular fibrocartilage (TFC) thickness attributable to disc regeneration of the TFC and TFC angle attributable to the suspension effect of ulnar shortening on the TFC. QUESTIONS/PURPOSES: The purposes of this study were (1) to compare preoperative and postoperative TFC thickness and TFC angle on MR images to quantitatively evaluate the effect of ulnar shortening osteotomy on disc regeneration and the suspension effect on the TFC; and (2) to assess whether changes in TFC thickness and TFC angle correlated with the Mayo wrist score. METHODS: Between 1995 and 2008, 256 patients underwent ulnar shortening osteotomy for TFCC injuries. The minimum followup was 24 months (mean, 51 months; range, 24 210 months). A total of 79 patients (31%) with complete followup including preoperative and postoperative MR images and the Mayo wrist score was included in this retrospective study. Evaluation of the postoperative MR images and the Mayo wrist score were performed at the final followup. The remaining 177 patients did not undergo postoperative MRI, or they had a previous fracture, large tears of the disc proper, or were lost to followup. Two orthopaedists, one of whom performed the surgeries, measured the TFC thickness and the TFC angle on coronal MR images before and after surgery for each patient. Correlations of the percent change in the TFC thickness and the magnitude of TFC angle change with age, sex, postoperative MR images, extent of ulnar shortening, preoperative ulnar variance, and postoperative Mayo wrist score were assessed. RESULTS: Stepwise regression analysis showed a correlation between the percent change in TFC thickness and preoperative ulnar variance (R2=0.21; beta=-0.33; 95% CI, -0.11 to 0.01; p=0.01) and between the magnitude of change in the TFC angle and the extent of ulnar shortening (R2=0.18; beta=-0.29; 95% CI, -5.8 to 0.29; p=0.03). The Mayo wrist score was not correlated with the percent change in TFC thickness or the magnitude of change in the TFC angle. CONCLUSIONS: These results suggest that, in patients with TFCC injury with a smaller preoperative ulnar variance, a high residual potential for regeneration in the disc proper was seen after ulnar shortening osteotomy, and correlated with the extent of ulnar shortening and the suspension effect on TFC. However, there was no correlation between disc regeneration or the suspension effect on TFC and the Mayo wrist score. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence. PMID- 25115586 TI - Letter to the editor: editorial: transition from training to practice--is there a better way? PMID- 25115585 TI - Highly crosslinked polyethylene improves wear but not surface damage in retrieved acetabular liners. AB - BACKGROUND: Highly crosslinked polyethylene (XLPE) is believed to demonstrate better wear resistance than conventional polyethylene (CPE) in total hip arthroplasty. QUESTIONS/PURPOSES: The purpose of this study was to compare visual damage scores and micro-CT measurements of penetration, a surrogate for wear, between matched retrieved XLPE and CPE acetabular liners. METHODS: Thirteen XLPE acetabular liners were matched in terms of implant design (all were of the same design), patient age, sex, liner dimensions, duration of implantation, and reason for revision to a group of CPE liners that were retrieved in the same time period. Penetration resulting from the combination of wear and creep in the two groups of liners was measured with micro-CT. Surface damage was scored by two blinded observers using a surface damage system that considers the seven common damage modes: pitting, scratching, burnishing, abrasions, impingement, embedded debris, and delamination, and wear patterns were documented. RESULTS: There was no difference (p=0.32) in total damage score between the XLPE group (14+/-4) and the CPE group (15+/-5). However, there was three times greater penetration (odds ratio, 3.1; confidence interval, 2.3-5.1; p<0.001) in the CPE group (0.18+/-0.09 mm/year) than in the XLPE group (0.05+/-0.07 mm/year). There was less volumetric loss in XLPE (82+/-SD 134 mm3) versus the CPE group (350+/-SD 342 mm3; p=0.017). CONCLUSIONS: XLPE liners undergo less penetration as a result of creep and wear than CPE liners based on quantitative measurements provided by micro-CT, which was not apparent using damage scoring alone. This demonstrates the use of three dimensional imaging techniques such as micro-CT for quantifying wear in retrieval studies. CLINICAL RELEVANCE: In this study, XLPE had less wear but similar damage scores than CPE, allaying concerns that the beneficial wear properties of XLPE might come with a tradeoff arising from the increased brittleness of that material. PMID- 25115588 TI - CORR Insights(r): the Otto Aufranc Award: modifiable versus nonmodifiable risk factors for infection after hip arthroplasty. PMID- 25115587 TI - Collateral ligament laxity in knees: what is normal? AB - BACKGROUND: Proper alignment and balancing of soft tissues of the knee are important goals for TKA. Despite standardized techniques, there is no consensus regarding the optimum amount of collateral ligament laxity one should leave at the end of the TKA. QUESTIONS/PURPOSES: I asked (1) what is the collateral laxity in young healthy volunteers, and (2) is there a difference in collateral laxity between males and females. METHODS: The femorotibial mechanical angle (FTMA) was measured in 314 knees in healthy volunteers aged 19 to 35 years. Subjects with a history of pain, malalignment, dysplasia, or trauma were excluded. Twenty-five knees were excluded because the hip center could not be acquired, and 22 were excluded because of a history of pain and trauma, leaving 267 knees for inclusion in the study. Of these, 155 were from men and 112 were from women. A validated method using a computer navigation system was used to obtain the measurements. A 10-Nm torque was used to stress the knee in varus and valgus at 0 degrees extension and 15 degrees flexion. An independent t-test and ANOVA were applied to the data to calculate any significant difference between groups (p<0.05). RESULTS: The mean (SD) unstressed supine FTMA was varus of 1.2 degrees (SD, 4 degrees ) in 0 degrees extension and varus of 1.2 degrees (SD, 4.4 degrees ) in 15 degrees flexion (p=0.88). On varus torque of 10 Nm, the supine FTMA changed by a mean of 3.1 degrees (SD, 2 degrees ) (95% CI, 2.4 degrees -3.8 degrees ; p<0.001) in 0 degrees extension and 6.9 degrees (SD, 2.6 degrees ) (95% CI, 6.2 degrees -7.7 degrees ; p<0.001) in 15 degrees flexion. On valgus torque of 10 Nm, the FTMA changed by a mean of 4.6 degrees (SD, 2.2 degrees ) (95% CI, 3.9 degrees -5.3 degrees ; p<0.001) in 0 degrees extension and 7.9 degrees (SD, 3.4 degrees ) (95% CI, 7.1 degrees -8.7 degrees ; p<0.001) in 15 degrees flexion. The mean unstressed FTMA in 0 degrees extension was varus of 1.7 degrees (SD, 4 degrees ) in men and 0.4 degrees (SD, 3.9 degrees ) in women (p=0.01). Differences in collateral ligament laxity were seen between men and women (p<0.001 for valgus torque and 0.035 for varus torque in 15 degrees flexion). With valgus torque at 0 degrees flexion, the supine FTMA change was valgus of 4.2 degrees (SD, 2.0 degrees ) for men and 5.0 degrees (SD, 2.4 degrees ) for women, while at 15 degrees flexion the FTMA change was valgus 7.6 degrees (SD, 3.6 degrees ) for men and 8.3 degrees (SD, 3.2 degrees ) for women With varus torque at 0 degrees flexion, additional varus was -3.0 degrees (SD, 1.8 degrees ) for men and -3.3 degrees (SD, 2.2 degrees ) for women, while at 15 degrees flexion, varus was -7.0 degrees SD, (2.5 degrees ) for men and -6.9 degrees (SD, 2.8 degrees ) for women. CONCLUSIONS: The collateral laxity in young healthy volunteers was quantified in this study. The collateral ligament laxity is variable in different persons. In addition, ligaments in women are more lax than in men in valgus stress. CLINICAL RELEVANCE: This study was conducted on young, healthy knees. Whether the findings are applicable to arthritic knees and replaced knees needs additional evaluation. However the findings provide a baseline from which to work in the evaluation of arthritic knees and in the case of TKA. PMID- 25115589 TI - Has the incidence of thoracolumbar spine injuries increased in the United States from 1998 to 2011? AB - BACKGROUND: While most motor vehicle crash (MVC)-related injuries have been decreasing, one study showed increases in MVC-related spinal fractures from 1994 to 2002 in Wisconsin. To our knowledge, no studies evaluating nationwide trends of MVC-related thoracolumbar spine injuries have been published. Such fractures can cause pain, loss of functionality or even death. If the incidence of such injuries is increasing, it may provide a motive for reassessment of current vehicle safety design. QUESTIONS/PURPOSES: We questioned whether the incidence of thoracolumbar spine injuries increased in the United States population with time (between 1998 and 2011), and if there was an increased incidence of thoracolumbar injuries, whether there were identifiable compensatory "trade-off injury" patterns, such as reductions in sacropelvic injuries. PATIENTS AND METHODS: Institutional review board approval was obtained for retrospective review of three national databases: the National Trauma Databank(r) (NTDB(r)), 2002-2006, National Automotive Sampling System (NASS), 2000-2011, and National Inpatient Sample (NIS), 1998-2007. In each database, the total number of MVC-related injuries and the number of MVC-related thoracolumbar injuries per year were identified using appropriate Abbreviated Injury Scale (AIS) or ICD-9 codes. Sacropelvic injuries also were identified to evaluate their potential as trade off injuries. Poisson regression models adjusting for age were used to analyze trends in the data with time. RESULTS: All databases showed increases in MVC related thoracolumbar spine injuries when adjusting for age with time. These age adjusted relative annual percent increases ranged from 8.22% (95% CI, 5.77% 10.72%; p<0.001) using AIS of 2 or more (AIS2 +) injury codes in the NTDB(r), 8.59% (95% CI, 5.88%-11.37%; p<0.001) using ICD-9 codes in the NTDB(r), 8.12% (95% CI, 7.20%-9.06%; p<0.001) using ICD-9 codes in the NIS, and 8.10 % (95% CI 5.00%-11.28%; p<0.001) using AIS2+ injury codes in the NASS. As these thoracolumbar injuries have increased, there has been no consistent trend toward a compensatory reduction in terms of sacropelvic injuries. CONCLUSIONS: While other studies have shown that rates of many MVC-related injuries are declining with time, our data show increases in the incidence of thoracolumbar injury. Although more sensitive screening tools likely have resulted in earlier and increased recognition of these injuries, it cannot be stated for certain that this is the only driver of the increased incidence observed in this study. As seatbelt use has continued to increase, this trend may be the result of thoracolumbar injuries as trade-offs for other injuries, although in our study we did not see a compensatory decrease in sacropelvic injuries. Investigation evaluating the root of this pattern is warranted. PMID- 25115590 TI - SARP19 and vdg3 gene families are functionally related during abalone metamorphosis. AB - The transcriptional activity of the SARP19-I1 and vdg3-I1 genes increases over tenfold when Haliotis diversicolor larvae shift from the pelagic to benthic lifestyle, signifying the important role of these genes during abalone metamorphosis. In this study, eight paralogous SARP19 genes and six paralogous vdg3 genes were identified from H. diversicolor transcriptomes. Phylogenetic analyses were performed, and the spatio-temporal expression patterns of these genes were separately determined by quantitative polymerase chain reaction (qPCR) and whole mount in situ hybridization (WMISH). Five SARP19 paralogs and five vdg3 paralogs showed at least a tenfold increase in expression after settlement. Among these differentially expressed genes, three SARP19 paralogs and four vdg3 paralogs were verified as being spatially expressed in the digestive glands of newly settled postlarvae. We proposed that a hypothesis of coevolution between the two gene families might explain the similarities in their expression patterns and their phylogenetics. PMID- 25115592 TI - Looking into meta-atoms of plasmonic nanowire metamaterial. AB - Nanowire-based plasmonic metamaterials exhibit many intriguing properties related to the hyperbolic dispersion, negative refraction, epsilon-near-zero behavior, strong Purcell effect, and nonlinearities. We have experimentally and numerically studied the electromagnetic modes of individual nanowires (meta-atoms) forming the metamaterial. High-resolution, scattering-type near-field optical microscopy has been used to visualize the intensity and phase of the modes. Numerical and analytical modeling of the mode structure is in agreement with the experimental observations and indicates the presence of the nonlocal response associated with cylindrical surface plasmons of nanowires. PMID- 25115591 TI - Antagonistic role of CotG and CotH on spore germination and coat formation in Bacillus subtilis. AB - Spore formers are bacteria able to survive harsh environmental conditions by differentiating a specialized, highly resistant spore. In Bacillus subtilis, the model system for spore formers, the recently discovered crust and the proteinaceous coat are the external layers that surround the spore and contribute to its survival. The coat is formed by about seventy different proteins assembled and organized into three layers by the action of a subset of regulatory proteins, referred to as morphogenetic factors. CotH is a morphogenetic factor needed for the development of spores able to germinate efficiently and involved in the assembly of nine outer coat proteins, including CotG. Here we report that CotG has negative effects on spore germination and on the assembly of at least three outer coat proteins. Such negative action is exerted only in mutants lacking CotH, thus suggesting an antagonistic effect of the two proteins, with CotH counteracting the negative role of CotG. PMID- 25115593 TI - Gross Morphometric Studies on the Tongue, Buccal Cavity and Hard Palate of the Fruit Bat (Eidolon helvum). AB - This study was designed to assess the gross morphometric studies of the tongue, hard palate and buccal cavity of the fruit bat (Eidolon helvum). Sixty bats of both sexes were used for this study. The tongue was excised, and the weight and various linear measurements were determined. Linear measurements were also determined on the hard palate. The gross distribution of the lingual papillae was observed to be the same in both sexes; values obtained for the weight and length of the tongue were higher in the females, although no statistically significant differences were observed (P > 0.05). The number of ridges on the hard palate displayed sexual dimorphism. Results obtained from this study may find application in the field of comparative and clinical anatomy of wildlife and also in feeding physiology. PMID- 25115594 TI - Biocompatibility and efficacy of collagen/gelatin sponge scaffold with sustained release of basic fibroblast growth factor on vocal fold fibroblasts in 3 dimensional culture. AB - OBJECTIVE: Treatment of vocal fold scarring remains challenging. We have previously reported the therapeutic effects of local injection of basic fibroblast growth factor (bFGF) in animal models and humans. A novel collagen/gelatin sponge (CGS) is capable of sustained release of bFGF, which compensates for its quick absorption in vivo, avoiding multiple injections. This study aimed to evaluate the biocompatibility and efficacy of the CGS in rat vocal fold fibroblasts prior to human trials. METHODS: Fibroblasts extracted from Sprague-Dawley rat vocal folds were seeded onto a CGS and then cultivated with bFGF at concentrations of 0, 10, and 100 ng/mL. Vocal fold fibroblast morphology, adhesion, proliferation, and gene expression were measured under these 3 dimensional conditions. RESULTS: Cells adhered to the CGS from day 1. Although no significant differences in cell morphology were detected, cell proliferation was accelerated by bFGF administration. Expression of endogenous bFGF and hepatocyte growth factor was significantly up-regulated at 10 ng/mL bFGF. The expression of procollagen I and procollagen III was significantly suppressed, whereas HAS-1 and HAS-2 were up-regulated at 10 and 100 ng/mL bFGF. CONCLUSION: The collagen/gelatin sponge is biocompatible with vocal fold fibroblasts and may be useful as a bFGF drug delivery system for the treatment of scarred vocal folds. PMID- 25115595 TI - Reinforcer magnitude and rate dependency: evaluation of resistance-to-change mechanisms. AB - Under many circumstances, reinforcer magnitude appears to modulate the rate dependent effects of drugs such that when schedules arrange for relatively larger reinforcer magnitudes rate dependency is attenuated compared with behavior maintained by smaller magnitudes. The current literature on resistance to change suggests that increased reinforcer density strengthens operant behavior, and such strengthening effects appear to extend to the temporal control of behavior. As rate dependency may be understood as a loss of temporal control, the effects of reinforcer magnitude on rate dependency may be due to increased resistance to disruption of temporally controlled behavior. In the present experiments, pigeons earned different magnitudes of grain during signaled components of a multiple FI schedule. Three drugs, clonidine, haloperidol, and morphine, were examined. All three decreased overall rates of key pecking; however, only the effects of clonidine were attenuated as reinforcer magnitude increased. An analysis of within-interval performance found rate-dependent effects for clonidine and morphine; however, these effects were not modulated by reinforcer magnitude. In addition, we included prefeeding and extinction conditions, standard tests used to measure resistance to change. In general, rate-decreasing effects of prefeeding and extinction were attenuated by increasing reinforcer magnitudes. Rate-dependent analyses of prefeeding showed rate-dependency following those tests, but in no case were these effects modulated by reinforcer magnitude. The results suggest that a resistance-to-change interpretation of the effects of reinforcer magnitude on rate dependency is not viable. PMID- 25115596 TI - Effects of Withania somnifera on oral ethanol self-administration in rats. AB - Recent evidence has shown that Withania somnifera Dunal (Ashwagandha or Indian ginseng), a herbal remedy used in traditional medicine, impairs morphine-elicited place conditioning. Here, we investigated the effect of W. somnifera roots extract (WSE) on motivation for drinking ethanol using operant self administration paradigms. Wistar rats were trained to self-administer ethanol (10%) by nose-poking. The effects of WSE (25-75 mg/kg) were evaluated on acquisition and maintenance, on ethanol breakpoint under a progressive-ratio schedule of reinforcement and on the deprivation effect and reinstatement of seeking behaviours. Moreover, on the basis of the recent suggestion of an involvement of GABAB receptors in WSE central effects, we studied the interaction between WSE and GABAB ligands. The effect of WSE on saccharin (0.05%) oral self administration was also tested. The results show that WSE reduced the acquisition, maintenance and breakpoint of ethanol self-administration. WSE also reduced the deprivation effect, reinstatement of ethanol-seeking behaviours and saccharin reinforcement. Furthermore, the GABAB receptor antagonist, phaclofen, counteracted the ability of WSE to impair the maintenance of ethanol self administration. These findings show that WSE, by an action that may involve GABAB receptors, impairs motivation for drinking ethanol and suggest that further investigations should be performed to determine whether W. somnifera may represent a new approach for the management of alcohol abuse. PMID- 25115597 TI - Improving primary care through information. A Wonca keynote paper. AB - Information from health care encounters across the entire health care spectrum, when consistently collected, analysed and applied can provide a clearer picture of patients' history as well as current and future needs through a better understanding of their morbidity burden and health care experiences. It can facilitate clinical activity to target limited resources to those patients most in need through risk adjustment mechanisms that consider the morbidity burden of populations, and it can help target quality improvement and cost saving activities in the right places. It can also open the door to a new chapter of evidence-based medicine around multi-morbidity. In summary, it can support a better integrated health system where primary care can provide continuous, coordinated, and comprehensive person-centred care to those who could benefit most. This paper explores the potential uses of information collected in electronic health records (EHRs) to inform case-mix and predictive modelling, as well as the associated challenges, with a particular focus on their application to primary care. PMID- 25115598 TI - A mini review on renewable sources for biofuel. AB - Rapid growth in both global energy demand and carbon dioxide emissions associated with the use of fossil fuels has driven the search for alternative sources which are renewable and have a lower environmental impact. This paper reviews the availability and bioenergy potentials of the current biomass feedstocks. These include (i) food crops such as sugarcane, corn and vegetable oils, classified as the first generation feedstocks, and (ii) lignocellulosic biomass derived from agricultural and forestry residues and municipal waste, as second generation feedstocks. The environmental and socioeconomic limitations of the first generation feedstocks have placed greater emphasis on the lignocellulosic biomass, of which the conversion technologies still faces major constraints to full commercial deployment. Key technical challenges and opportunities of the lignocellulosic biomass-to-bioenergy production are discussed in comparison with the first generation technologies. The potential of the emerging third generation biofuel from algal biomass is also reviewed. PMID- 25115599 TI - Aerobic direct C-H arylation of nonbiased olefins. AB - An efficient ligand-promoted biomimetic aerobic oxidative dehydrogenative cross coupling between arenes and nonbiased olefins is presented. Acridine as a ligand was found to significantly enhance the rate, the yield, and the scope of the reaction under ambient oxygen pressure, providing a variety of alkenylarenes via an environmentally friendly procedure. PMID- 25115604 TI - Drivers influencing streamflow changes in the Upper Turia basin, Spain. AB - Many rivers across the world have experienced a significant streamflow reduction over the last decades. Drivers of the observed streamflow changes are multiple, including climate change (CC), land use and land cover changes (LULCC), water transfers and river impoundment. Many of these drivers inter-act simultaneously, making it difficult to discern the impact of each driver individually. In this study we isolate the effects of LULCC on the observed streamflow reduction in the Upper Turia basin (east Spain) during the period 1973-2008. Regression models of annual streamflow are fitted with climatic variables and also additional time variant drivers like LULCC. The ecohydrological model SWAT is used to study the magnitude and sign of streamflow change when LULCC occurs. Our results show that LULCC does play a significant role on the water balance, but it is not the main driver underpinning the observed reduction on Turia's streamflow. Increasing mean temperature is the main factor supporting increasing evapotranspiration and streamflow reduction. In fact, LULCC and CC have had an offsetting effect on the streamflow generation during the study period. While streamflow has been negatively affected by increasing temperature, ongoing LULCC have positively compensated with reduced evapotranspiration rates, thanks to mainly shrubland clearing and forest degradation processes. These findings are valuable for the management of the Turia river basin, as well as a useful approach for the determination of the weight of LULCC on the hydrological response in other regions. PMID- 25115606 TI - Mercury biogeochemical cycling and processes: implications for human and ecosystem health. PMID- 25115608 TI - Shrinkage assessment of low shrinkage composites using micro-computed tomography. AB - OBJECTIVES: The aim of this study was to quantify the polymerization volumetric shrinkage of one regular and two low shrinkage bulk fill composites in class I cavities with or without an adhesive layer, using three-dimensional (3D) micro computed tomography (MUCT). METHODS: Class I cavity preparations (2.5 mm depth * 4 mm length * 4 mm wide) were standardized in 36 extracted human third molars, which were randomly divided in six groups (n = 6 each) as follows: Group VIT (regular composite without bonding agent); Group SDR (low shrinkage flowable composite without bonding agent); Group TET (low shrinkage composite without bonding agent); Group VIT/P (regular composite with bonding agent); Group SDR/X (low shrinkage flowable composite with bonding agent); TET/T (low shrinkage composite with bonding agent). Each tooth was scanned via uCT at cavity preparation, immediately after cavity filling, and after light-curing. Acquired MUCT data were imported into Amira software for analysis and volume values evaluated between steps from cavity preparation until light-curing. RESULTS: Both low shrinkage composites showed a significantly less volumetric shrinkage than VIT. The use of dental adhesive significantly decreased the average volumetric contraction similarly for the three composites, by about 20%. CONCLUSION: Both low shrinkage composites showed less volumetric polymerization contraction than the regular composite. The use of dental adhesive decreased the total volumetric shrinkage for all evaluated composites. PMID- 25115605 TI - Predictors of serum polychlorinated biphenyl concentrations in Anniston residents. AB - The Anniston Community Health Survey was a community-based cross-sectional study of Anniston, Alabama, residents who live in close proximity to a former PCB production facility to identify factors associated with serum PCB levels. The survey comprises 765 Anniston residents who completed a questionnaire interview and provided a blood sample for analysis in 2005-2007. Several reports based on data from the Anniston survey have been previously published, including associations between PCB exposure and diabetes and blood pressure. In this study we examine demographic, behavioral, dietary, and occupational characteristics of Anniston survey participants as predictors of serum PCB concentrations. Of the 765 participants, 54% were White and 45% were African-American; the sample was predominantly female (70%), with a mean age of 55 years. Serum PCB concentrations varied widely between participants (range for sum of 35 PCBs: 0.11-170.4 ng/g wet weight). Linear regression models with stepwise selection were employed to examine factors associated with serum PCBs. Statistically significant positive associations were observed between serum PCB concentrations and age, race, residential variables, current smoking, and local fish consumption, as was a negative association with education level. Age and race were the most influential predictors of serum PCB levels. A small age by sex interaction was noted, indicating that the increase in PCB levels with age was steeper for women than for men. Significant interaction terms indicated that the associations between PCB levels and having ever eaten locally raised livestock and local clay were much stronger among African-Americans than among White participants. In summary, demographic variables and past consumption of locally produced foods were found to be the most important predictors of PCB concentrations in residents living in the vicinity of a former PCB manufacturing facility. PMID- 25115607 TI - Erythropoietin ameliorates the motor and cognitive function impairments in a rat model of hepatic cirrhosis. AB - Hepatic encephalopathy (HE) is a serious consequence of hepatic cirrhosis (HC). Previous studies have demonstrated cognitive impairments in both clinical and animal experiments of HC. Some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of HC. In the current study, the possible effect of erythropoietin (ERY) as a potent neuroprotective agent on motor and cognitive impairments induced by HC has been studied. Male Wistar rats (180-200 g) underwent bile duct ligation (BDL) or sham surgery. Administration of ERY (5,000 IU/kg, i.p., daily for three days) was initiated 2 weeks after surgery and lasted for the next 28 days. Open field, rotarod, Morris water maze and passive avoidance learning was used to evaluate the motor and cognitive function of the animals. ANOVA and repeated measures ANOVA were used to analyze the data. p < 0.05 was considered statistically significant. BDL rats had an increased level of hepatic enzymes and bilirubin. Impairment of balance function by BDL was reversed by ERY. Spatial and passive avoidance learning impairments observed in BDL rats were also reversed by chronic administration of ERY. ERY can be offered as a potential neuroprotective agent in the treatment of patients with HC that manifest mental dysfunctions. Though further studies are needed to clarify the exact mechanisms, the neuroprotective properties of ERY against BDL impairments were demonstrated in the current study. PMID- 25115609 TI - General Practitioner Supervisor assessment and teaching of Registrars consulting with Aboriginal patients - is cultural competence adequately considered? AB - BACKGROUND: General Practitioner (GP) Supervisors have a key yet poorly defined role in promoting the cultural competence of GP Registrars who provide healthcare to Aboriginal and Torres Strait Islander people during their training placements. Given the markedly poorer health of Indigenous Australians, it is important that GP training and supervision of Registrars includes assessment and teaching which address the well documented barriers to accessing health care. METHODS: A simulated consultation between a GP Registrar and an Aboriginal patient, which illustrated inadequacies in communication and cultural awareness, was viewed by GP Supervisors and Medical Educators during two workshops in 2012. Participants documented teaching points arising from the consultation which they would prioritise in supervision provided to the Registrar. Content analysis was performed to determine the type and detail of the planned feedback. Field notes from workshop discussions and participant evaluations were used to gain insight into participant confidence in cross cultural supervision. RESULTS: Sixty four of 75 GPs who attended the workshops participated in the research. Although all documented plans for detailed teaching on the Registrar's generic communication and consultation skills, only 72% referred to culture or to the patient's Aboriginality. Few GPs (8%) documented a plan to advise on national health initiatives supporting access for Aboriginal and Torres Strait Islander people. A lack of Supervisor confidence in providing guidance on cross cultural consulting with Aboriginal patients was identified. CONCLUSIONS: The role of GP Supervisors in promoting the cultural competence of GP Registrars consulting with Aboriginal and Torres Strait Islander patients could be strengthened. A sole focus on generic communication and consultation skills may lead to inadequate consideration of the health disparities faced by Indigenous peoples and of the need to ensure Registrars utilise health supports designed to decrease the disadvantage faced by vulnerable populations. PMID- 25115610 TI - Mutations in microRNA binding sites of CEP genes involved in cancer. AB - The CEP genes play a pivotal role in the replication of the cell. CEP family proteins form the major constituents of the centrosome and play a prominent role in centriole biogenesis and in cell replication. Alteration in CEP genes will result in disruption of cell cycle that may in turn cause cancer. In our study, we found that 16 of the CEP genes are a potential target to miRNA that binds to complementary sequences in 3'untranslated regions (UTR) of mRNA and stop them from translation. Single nucleotide polymorphisms (SNPs) occurring naturally in such miRNA binding site can alter the miRNA: mRNA interaction and can significantly alter gene expression. We developed a systematic computational pipeline that integrates data from well-established databases, followed stringent selection criteria and identified a panel of 44 high-confidence SNPs that may impair miRNA target sites in the 3'UTR of 16 genes. Further we performed expression analysis to shed light on the potential tissues that might be affected by mutation, enrichment analysis to find the metabolic functions of the gene, and network analysis to highlight the important interactions of CEP genes with other genes to provide insight that complex network will be disturbed upon mutation. In this study, we explored and prioritised the SNPs in CEP gene which could act as a potential target in centrosome-associated human disease. Our analysis would provide a thoughtful insight to wet lab researches to understand the expression pattern of CEP genes and binding phenomenon of mRNA and miRNA upon mutation, which is responsible for inhibition of translation process at genomic levels. PMID- 25115611 TI - Is rs8099917 polymorphism of IL-28B gene a good predictor of response to therapy of HCV than rs12979860? An Egyptian study. AB - Hepatitis C virus (HCV) infection is the major etiology of chronic liver disease. Polymorphisms in the IL-28B gene region are important in predicting outcome following therapy for chronic hepatitis C virus infection. The aim of this study was to detect the relationship between IL-28B polymorphism and responses to therapy in patients infected with genotype 4. This study included one hundred chronic hepatitis C patients infected with genotype 4, received PEG-IFNalpha2b plus ribavirin for 24 weeks, as well as, 20 healthy subjects serving as control. Clinical and laboratory parameters, including genetic variation near the IL-28B gene (rs8099917 and rs12979860), were assessed. The results of this study showed significant difference between responders and non-responders as regard SNPs in the interleukin 28B gene at rs8099917 and rs12979860. In rs8099917, TT genotypes had more frequency in responders than GG genotypes. On the other hand, CC genotype in rs12979860 had more frequency in responders than TT genotype. By multiple regression analysis, rs8099917 (TT), total bilirubin, and prothrombin time were independent factors affecting the response to treatment. This results demonstrate that in HCV genotype 4-infected patients, rs12979860 (CC) and rs8099917 (TT) genotypes may identify patients who are likely to respond to treatment. IL-28B SNPs are good predictors of response to combination therapy of HCV. PMID- 25115612 TI - Expression of MIG/CXCL9 in cystic fibrosis and modulation of its activities by elastase of Pseudomonas aeruginosa. AB - In cystic fibrosis (CF), colonization of the airways with Pseudomonas aeruginosa is associated with disease deterioration. The mechanism behind the disease progression is not fully understood. The present work shows that the antibacterial chemokine MIG/CXCL9 is present in the airways and in sputum of CF patients. MIG/CXCL9 showed high bactericidal activity against. P. aeruginosa, including some strains from the airways of CF patients. Full-length MIG/CXCL9 was detected in sputum from healthy controls and CF patients colonized with P. aeruginosa. However, degraded MIG/CXCL9 was only found in CF sputum. In vitro, elastase of P. aeruginosa cleaved off a fragment of similar size and two additional fragments from MIG/CXCL9. The fragments showed less bactericidal activity against P. aeruginosa compared with the full-length protein. The fragments did not activate the MIG/CXCL9 receptor CXCR3 (expressed e.g. by NK cells, mast cells, and activated T cells) but instead displayed noncompetitive inhibition. In vitro, a decrease in CXCR3-bearing cells was found within and in the proximity of the bronchial epithelium of CF lung tissue compared with controls. Taken together, both bactericidal and cell-recruiting activities of MIG/CXCL9 are corrupted by P. aeruginosa through release of elastase, and this may contribute to impaired airway host defense in CF. PMID- 25115613 TI - Multi-scale simulations predict responses to non-invasive nerve root stimulation. AB - OBJECTIVE: Established biophysical neurone models have achieved limited success in reproducing electrophysiological responses to non-invasive stimulation of the human nervous system. This is related to our insufficient knowledge of the induced electric currents inside the human body. Despite the numerous research and clinical applications of non-invasive stimulation, it is still unclear which internal sites are actually affected by it. APPROACH: We performed multi-scale computer simulations that, by making use of advances in computing power and numerical algorithms, combine a microscopic model of electrical excitation of neurones with a macroscopic electromagnetic model of the realistic whole-body anatomy. MAIN RESULTS: The simulations yield responses consistent with those experimentally recorded following magnetic and electrical motor root stimulation in human subjects, and reproduce the observed amplitudes and latencies for a wide variety of stimulation parameters. SIGNIFICANCE: Our findings demonstrate that modern computational techniques can produce detailed predictions about which and where neurones are activated, leading to improved understanding of the physics and basic mechanisms of non-invasive stimulation and enabling potential new applications that make use of improved targeting of stimulation. PMID- 25115614 TI - De novo renal cell carcinoma in a kidney allograft with focus on contrast enhanced ultrasound. AB - The development of de novo renal cell carcinoma (RCC) in a transplanted kidney is a rare condition. Currently, this is the second case report of a 41-year-old man in whom carcinoma of a renal allograft was detected by contrast-enhanced ultrasound (CEUS). An abdominal CT scan was not conclusive enough to differentiate between septal enhancement of a cyst and a low vascularized tumor. CEUS confirmed a solid, homogeneously enhancing but hypoechoic and hypovascular lesion compared to the surrounding kidney parenchyma without septal enhancement. Therefore, the patient underwent nephron-sparing surgery (NSS), affirming papillary RCC type 2. Graft function remained unchanged postoperatively; 12 months after NSS, no local recurrence or distant metastasis was described. CEUS seems to be a minimally invasive and efficient imaging option if other diagnostic tools cannot clearly exclude RCC, with the advantage of wide-ranging use, especially in cases of impaired renal function. PMID- 25115615 TI - Prevalence of non-polypoid colorectal neoplasms in southern Brazil. AB - BACKGROUND AND AIM: Several studies suggest that non-polypoid lesions (NPL) show higher aggressiveness than polypoid lesions, particularly depressed lesions. The present study aimed to assess the prevalence of NPL and the presence of advanced histology in a Brazilian population. METHODS: Two thousand and sixty-seven superficial neoplastic lesions diagnosed in 1135 patients were analyzed. Lesions were classified as polypoid and non-polypoid (flat and depressed) types, and evaluated for site, size, and histology (adenoma with grade of dysplasia, or early cancer). RESULTS: Prevalence of NPL was 46.5%. NPL predominated in the right colon (62.9%), whereas polypoid lesions were detected mainly in the left colon (53.2%) (P < 0.001). NPL had a 34% higher probability of occurring in the right colon than polypoid lesions (P < 0.001). NPL were smaller than polypoid lesions (P = 0.03). There were 208 lesions >10 mm, of which 40 (19.2%) had advanced histology: 13% (18/138) of polypoid lesions; 27.3% (18/66) of flat lesions; and 100% (4/4) of depressed lesions (P < 0.001). Among 1859 neoplasms <=10 mm, only 18 (1%) had advanced histology, and 15 of them were depressed lesions (P < 0.001). Advanced histology was more commonly detected in NPL than in polypoid lesions (P = 0.007), with significant difference in size (P < 0.001). NPL showed more advanced histology than polypoid lesions (OR 2.06; P = 0.01), especially depressed lesions (OR 36.35; P < 0.001). Among all neoplasms, the prevalence of depressed lesions was 2.2%. CONCLUSION: NPL showed high prevalence and higher aggressiveness than polypoid lesions, especially the depressed type. PMID- 25115617 TI - Patients' perspectives on hemodialysis vascular access: a systematic review of qualitative studies. AB - BACKGROUND: Delayed creation of vascular access may be due in part to patient refusal and is associated with adverse outcomes. Concerns about vascular access are prevailing treatment-related stressors for patients on hemodialysis therapy. This study aims to describe patients' perspectives on vascular access initiation and maintenance in hemodialysis. STUDY DESIGN: Systematic review and thematic synthesis of qualitative studies. SETTING & POPULATION: Patients with chronic kidney disease who express opinions about vascular access for hemodialysis. SEARCH STRATEGY & SOURCES: MEDLINE, EMBASE, PsycINFO, CINAHL, reference lists, and PhD dissertations were searched to October 2013. ANALYTICAL APPROACH: Thematic synthesis was used to analyze the findings. RESULTS: From 46 studies involving 1,034 patients, we identified 6 themes: heightened vulnerability (bodily intrusion, fear of cannulation, threat of complications and failure, unpreparedness, dependence on a lifeline, and wary of unfamiliar providers), disfigurement (preserving normal appearance, visual reminder of disease, and avoiding stigma), mechanization of the body (bonded to a machine, internal abnormality, and constant maintenance), impinging on way of life (physical incapacitation, instigating family tension, wasting time, and added expense), self-preservation and ownership (task-focused control, advocating for protection, and acceptance), and confronting decisions and consequences (imminence of dialysis therapy and existential thoughts). LIMITATIONS: Non-English articles were excluded. CONCLUSIONS: Vascular access is more than a surgical intervention. Initiation of vascular access signifies kidney failure and imminent dialysis, which is emotionally confronting. Patients strive to preserve their vascular access for survival, but at the same time describe it as an agonizing reminder of their body's failings and "abnormality" of being amalgamated with a machine disrupting their identity and lifestyle. Timely education and counseling about vascular access and building patients' trust in health care providers may improve the quality of dialysis and lead to better outcomes for patients with chronic kidney disease requiring hemodialysis. PMID- 25115616 TI - A randomized, placebo-controlled trial of pentoxifylline on erythropoiesis stimulating agent hyporesponsiveness in anemic patients with CKD: the Handling Erythropoietin Resistance With Oxpentifylline (HERO) trial. AB - BACKGROUND: Erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia is common in chronic kidney disease (CKD). Pentoxifylline shows promise as a treatment for ESA-hyporesponsive anemia, but has not been rigorously evaluated. STUDY DESIGN: Multicenter, double-blind, randomized, controlled trial. SETTING & PARTICIPANTS: 53 adult patients with CKD stage 4 or 5 (including dialysis) and ESA-hyporesponsive anemia (hemoglobin<=120g/L and ESA resistance index [calculated as weight-adjusted weekly ESA dose in IU/kg/wk divided by hemoglobin concentration in g/L]>=1.0IU/kg/wk/g/L for erythropoietin-treated patients and >=0.005MUg/kg/wk/g/L for darbepoetin-treated patients). INTERVENTIONS: Pentoxifylline (400mg/d; n=26) or matching placebo (control; n=27) for 4 months. OUTCOMES: PRIMARY OUTCOME: ESA resistance index at 4 months; secondary outcomes: hemoglobin concentration, ESA dose, blood transfusion requirement, serum ferritin level and transferrin saturation, C-reactive protein level, adverse events, quality of life, and health economics. RESULTS: There was no statistically significant difference in ESA resistance index between the pentoxifylline and control groups (adjusted mean difference, -0.39 [95%CI, -0.89 to 0.10] IU/kg/wk/g/L; P=0.1). Pentoxifylline significantly increased hemoglobin concentration relative to the control group (adjusted mean difference, 7.6 [95%CI, 1.7-13.5] g/L; P=0.01). There was no difference in ESA dose between groups (-20.8 [95%CI, -67.2 to 25.7] IU/kg/wk; P=0.4). No differences in blood transfusion requirements, adverse events, or quality of life were observed between groups. Pentoxifylline cost A$88.05 (US $82.94) per person over the trial and produced mean savings in ESA cost of A$1,332 (US $1,255). The overall economic impact over the trial period was a saving of A$1,244 (US $1,172) per person for the pentoxifylline group compared with controls. LIMITATIONS: Sample size smaller than planned due to slow recruitment. CONCLUSIONS: Pentoxifylline did not significantly modify ESA hyporesponsiveness, but increased hemoglobin concentration. Further studies are warranted to determine whether pentoxifylline therapy represents a safe strategy for increasing hemoglobin levels in patients with CKD with ESA-hyporesponsive anemia. PMID- 25115619 TI - Predictors of anxiety in centenarians: health, economic factors, and loneliness. AB - BACKGROUND: Centenarians' psychological well-being is presently of great interest in psychogeriatric research but little is known about factors that specifically account for the presence of clinically relevant anxiety symptoms in this age group. This study examined the presence of anxiety and its predictors in a sample of centenarians and aims to contribute to a better understanding of anxiety determinants in extreme old age. METHODS: We examined how socio-demographic, health, functional, and social factors contribute to the presence of clinically significant anxiety symptoms in centenarians recruited from two Portuguese centenarian studies. The Geriatric Anxiety Inventory - Short Form (GAI-SF) was used to assess anxiety symptoms. RESULTS: A total of 97 centenarians (mean age 101.1 years; SD = 1.5 years; range = 100-108) with no/minor cognitive impairment were included. Clinically significant anxiety symptoms (GAI-SF >=3) were present in 45.4% (n = 44) of the sample. Main predictive factors included worse health perception, higher number of medical conditions, financial concerns related to medical expenses (income inadequacy) and loneliness. CONCLUSIONS: Results suggest that along with health status (subjective and objective), income inadequacy related to medical expenses and feeling lonely may predispose centenarians to clinically significant anxiety and be important to their overall well-being. Further research is needed on the repercussions of clinical anxiety in centenarians' quality of life and on co-morbid conditions (e.g. depression) at such advanced ages. PMID- 25115618 TI - Construct and concurrent validity of a patient-reported adverse drug event questionnaire: a cross-sectional study. AB - BACKGROUND: Direct patient-reported information about adverse drug events (ADEs) is important since it adds to healthcare professional-reported information about the safety of drugs. Previously, we developed an instrument to assess patient reported ADEs in research settings. The aim of this study is to assess the construct and concurrent validity of the questionnaire. METHODS: Patients on at least an oral glucose-lowering drug completed the ADE questionnaire, the World Health Organization Quality of Life-BREF, and the Treatment Satisfaction Questionnaire for Medication (TSQM). The ADE questionnaire assesses ADEs for any drug that the patient uses. Construct validity was assessed by testing whether patients reporting an ADE had a lower general quality of life and physical health than those not reporting an ADE, using Mann-Whitney U-tests and t-tests (significance level <0.05). For concurrent validity, we tested whether ADEs that patients associate with particular drugs in the ADE questionnaire are documented in the Summary of Product Characteristics (SPC) of those drugs, and whether patients who report an ADE with the use of metformin on the TSQM, mention metformin as a drug associated with an ADE on the ADE questionnaire. Agreement of 70% with the SPC was considered satisfactory. Sensitivity and positive predictive value (PPV) were calculated for the comparison with the TSQM, where 70% was used as the cut-off level for sufficient concurrent validity. RESULTS: We included 135 patients (mean age 64 years, 35% women). Patients who reported an ADE (N = 37) had a lower general quality of life and physical health than those not reporting an ADE (P < 0.05). For 78 of the 146 reported ADEs (53%), patients mentioned at least 1 particular drug associated with the ADE. After clustering related ADEs, this resulted in 56 patient-reported ADE-drug associations. Of these, 41 (73%) were in agreement with information in the SPC. Finally, the questionnaire had a sensitivity of 38% and PPV of 79% for assessing ADEs associated with metformin. CONCLUSIONS: The construct validity of the patient-reported ADE questionnaire was sufficient for reporting any versus no ADE, but the concurrent validity was only partly demonstrated. Therefore, the questionnaire needs to be adapted before it can be used. PMID- 25115620 TI - Stimulus-specific adaptation in the inferior colliculus of the mouse: anesthesia and spontaneous activity effects. AB - Rapid behavioral responses to unexpected events in the acoustic environment are critical for survival. Stimulus-specific adaptation (SSA) is the process whereby some auditory neurons respond better to rare stimuli than to repetitive stimuli. Most experiments on SSA have been performed under anesthesia, and it is unknown if SSA sensitivity is altered by the anesthetic agent. Only a direct comparison can answer this question. Here, we recorded extracellular single units in the inferior colliculus of awake and anesthetized mice under an oddball paradigm that elicits SSA. Our results demonstrate that SSA is similar, but not identical, in the awake and anesthetized preparations. The differences are mostly due to the higher spontaneous activity observed in the awake animals, which also revealed a high incidence of inhibitory receptive fields. We conclude that SSA is not an artifact of anesthesia and that spontaneous activity modulates neuronal SSA differentially, depending on the state of arousal. Our results suggest that SSA may be especially important when nervous system activity is suppressed during sleep-like states. This may be a useful survival mechanism that allows the organism to respond to danger when sleeping. PMID- 25115621 TI - Central arterial pulse waveform acquisition with a portable pen-like optical fiber sensor. AB - OBJECTIVE: Pulse waveform features related to cardiovascular pathologies and arterial stiffness have been extensively studied, and optical fiber sensors have been studied with an aim to simplify the pulse waveform acquisition in the carotid artery. In this paper, a novel optical fiber sensor to record pulse waveform in the carotid artery has been proposed. METHODS: The pulse waveform optical fiber sensor design, based on fiber Bragg gratings, is presented. The probe was characterized, and its response to controlled waveforms was studied. Finally, tests were performed on human subjects. RESULTS: The developed sensor has a displacement sensitivity of 21.2 pm/MUm, with ability to detect the carotid pulse wave in the neck surface, with a resolution of 1.3 mmHg. CONCLUSION: This study revealed a new technological approach for acquisition of the central pulse waveform. PMID- 25115622 TI - In response: ambulatory blood pressure measurement in pharmacies. PMID- 25115623 TI - Planar edge Schottky barrier-tunneling transistors using epitaxial graphene/SiC junctions. AB - A purely planar graphene/SiC field effect transistor is presented here. The horizontal current flow over one-dimensional tunneling barrier between planar graphene contact and coplanar two-dimensional SiC channel exhibits superior on/off ratio compared to conventional transistors employing vertical electron transport. Multilayer epitaxial graphene (MEG) grown on SiC(0001) was adopted as the transistor source and drain. The channel is formed by the accumulation layer at the interface of semi-insulating SiC and a surface silicate that forms after high vacuum high temperature annealing. Electronic bands between the graphene edge and SiC accumulation layer form a thin Schottky barrier, which is dominated by tunneling at low temperatures. A thermionic emission prevails over tunneling at high temperatures. We show that neglecting tunneling effectively causes the temperature dependence of the Schottky barrier height. The channel can support current densities up to 35 A/m. PMID- 25115624 TI - Effect of extraction technique on the content and antioxidant activity of crude extract of Anacyclus clavatus flowers and their essential oil composition. AB - Anacyclus clavatus is a plant used as food and remedy. The objective of this work was to study the effect of extraction technique on the antioxidant property, total phenol and flavonoid contents of crude extracts from A. clavatus flowers and their essential oil composition. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, ferric-reducing power, beta-carotene and total antioxidant capacity assays have demonstrated the significant antioxidant ability of different crude extracts obtained by using the following extraction methods: Soxhlet, microwave heating, heat reflux (HRE) and maceration. The activity of the extract obtained by HRE was the highest (112.06 +/- 2.89 MUg/mL) evaluated by the DPPH assay. Extraction of essential oil was performed by microwave-assisted hydro-distillation (MAHD) and by hydro-distillation (HD). A significant difference was observed in both essential oils, despite the common main family and major constituents, such as artemisia ketone (10.0 +/- 0.8% for MAHD vs. 6.5 +/- 0.5 for HD) and pinocarvone (4.1 +/- 0.4% for MAHD vs. 1.1 +/- 0.1% for HD). PMID- 25115625 TI - Synthesis of tetrahydropyridine derivatives through a modular assembly reaction using 3,4-dihydropyran as dual substrate and template. AB - A concise method to synthesize 1,2,3,4-tetrahydropyridines is described that involves the use of 2-alkoxy-3,4-dihydropyran as a modular precursor to react with aniline and a nucleophile. In this method, the heteroatom of the dihydropyran ring was replaced by nitrogen of aniline while the nucleophile attached to its adjacent position. Various druglike polyheterocycles were prepared with this method by using NH2-containing 1,5- or 1,4-bisnucleophiles. PMID- 25115626 TI - Scaffold hopping of sampangine: discovery of potent antifungal lead compound against Aspergillus fumigatus and Cryptococcus neoformans. AB - Discovery of novel antifungal agents against Aspergillus fumigatus and Cryptococcus neoformans remains a significant challenge in current antifungal therapy. Herein the antifungal natural product sampangine was used as the lead compound for novel antifungal drug discovery. A series of D-ring scaffold hopping derivatives were designed and synthesized to improve antifungal activity and water solubility. Among them, the thiophene derivative S2 showed broad-spectrum antifungal activity, particularly for Aspergillus fumigatus and Cryptococcus neoformans. Moreover, compound S2 also revealed better water solubility than sampangine, which represents a promising antifungal lead compound for further structural optimization. PMID- 25115628 TI - In vitro dynamic degradation behavior of new magnesium alloy for orthopedic applications. AB - We report on methodologies for use in the design of a biodegradable Mg alloy appropriate for load-bearing but temporary orthopedic implant applications. Comparative studies of Mg-5Ca and Mg-5Ca-1Zn were conducted to explore the effects of a combination of minor alloying and hot extrusion, on the alloy's mechanical properties and corrosion resistance. The extruded Mg-5Ca-1Zn exhibited high ultimate compressive strength of 385 MPa and suffered no significant structural degradation even after immersion in simulated body fluid for 30 days. Mg-5Ca-1Zn alloy showed the mechanical strength and controlled corrosion rate to be considered as an ideal candidate for biodegradable orthopedic implant material. PMID- 25115627 TI - Moderate hypoxia influences potassium outward currents in adipose-derived stem cells. AB - Moderate hypoxic preconditioning of adipose-derived stem cells (ASCs) enhances properties such as proliferation and secretion of growth factors, representing a valuable strategy to increase the efficiency of cell-based therapies. In a wide variety of cells potassium (K+) channels are key elements involved in the cellular responses to hypoxia, suggesting that ASCs cultured under low oxygen conditions may display altered electrophysiological properties. Here, the effects of moderate hypoxic culture on proliferation, whole-cell currents, and ion channel expression were investigated using human ASCs cultured at 5% and 20% oxygen. Although cell proliferation was greatly enhanced, the dose-dependent growth inhibition by the K+ channel blocker tetraethylammonium (TEA) was not significantly affected by hypoxia. Under both normoxic and hypoxic conditions, ASCs displayed outward K+ currents composed by Ca2+-activated, delayed rectifier, and transient components. Hypoxic culture reduced the slope of the current voltage curves and caused a negative shift in the voltage activation threshold of the whole-cell currents. However, the TEA-mediated shift of voltage activation threshold was not affected by hypoxia. Semiquantitative real-time RT-PCR revealed that expression of genes encoding for various ion channels subunits related to oxygen sensing and proliferation remained unchanged after hypoxic culture. In conclusion, outward currents are influenced by moderate hypoxia in ASCs through a mechanism that is not likely the result of modulation of TEA-sensitive K+ channels. PMID- 25115629 TI - Validation and reference ranges of hair cortisol measurement in healthy children. AB - BACKGROUND: Cortisol is produced in a circadian rhythm controlled by the hypothalamus-pituitary-adrenal axis, making it cumbersome to measure long-term cortisol exposure. Hair has proven to be a reliable matrix for long-term cortisol measurement in adults and can be used as diagnostic tool for (cyclic) Cushing's syndrome. The diagnostic applicability in children has not been studied, nor have the effects of development and hair care been evaluated in children. We aimed to establish reference ranges of hair cortisol concentrations (HCC) in healthy children and to evaluate the effects of age, gender, puberty and characteristics of hair care. METHODS: In 128 healthy children aged 4-14 years, HCC were measured in a small 3-cm hair lock from the back of the head. RESULTS: HCC increased with age (p = 0.04) up to age 10 years, with a mean of 5.0, 5.8, 6.8 and 8.5 pg/mg at age 4-5, 6-7, 8-9 and 10-14 years, respectively. Children aged 4-7 years had significantly lower HCC compared to healthy adults (p = 0.007). We did not find any influence of gender, puberty or hair care characteristics on hair cortisol. CONCLUSION: HCC can be reliably measured in childhood, and reference ranges increase with age. HCC in children are not dependent on hair care or hair characteristics. PMID- 25115630 TI - Diaminoglyoxime as a versatile reagent in the synthesis of bis(1,2,4 oxadiazoles), 1,2,4-oxadiazolyl-quinazolines and 1,2,4-oxadiazolyl benzothiazinones. AB - The synthesis of bis(1,2,4-oxadiazoles), 1,2,4-oxadiazolyl-quinazolines, and 1,2,4-oxadiazolyl-benzothiazinones has been investigated by the reaction of diaminoglyoxime with various ketones and methyl 2-aminobenzoate, 2-amino-5 chlorophenyl)(phenyl)methanone, and 2-mercapto benzoic acid in acetic acid either a catalyst or solvent at 100 degrees C. PMID- 25115631 TI - Expression of Neural Wiskott-Aldrich Syndrome Protein in Clear Cell Renal Cell Carcinoma and Its Correlation with Clinicopathological Features. AB - INTRODUCTION: Neural Wiskott-Aldrich syndrome protein (N-WASP) expression is associated with tumor cell invasion and migration. However, its expression status in clear cell renal cell carcinoma (CCRCC) remains unclear. We examined the level of N-WASP in CCRCC and its association with clinicopathological features characteristic. MATERIALS AND METHODS: 73 CCRCC patients who underwent radical nephrectomy or partial nephrectomy were enrolled. Immunohistochemical staining for N-WASP was performed on tissue microarrays constructed from tumor and para tumor tissue obtained from these patients. The difference in N-WASP expression between tumor tissue and adjacent normal renal tissue was examined. Correlations between N-WASP expression in the tumor and clinicopathological parameters were analyzed and the relationship between N-WASP expression and overall survival also assessed. Uni- and multivariate survival analyses were performed. RESULTS: N-WASP expression was significantly reduced in tumor tissues and was significantly related to the histological grade of CCRCC. A higher level of N-WASP expression in the tumor was associated with relatively poor survival in CCRCC patients. The level of N-WASP expression, age at time of surgery, and histological grade were all responsible for clinical outcome in CCRCC patients. N-WASP was an independent predictor for overall survival. CONCLUSIONS: N-WASP was downregulated in CCRCC and could serve as a prognostic biomarker for predicting clinical outcome of CCRCC. PMID- 25115632 TI - Efficiency of pretreatment risk stratification systems for prostate cancer in a Japanese population treated with radical prostatectomy. AB - OBJECTIVE: To determine whether the currently available pretreatment risk classification systems are applicable in Japanese prostate cancer patients. METHODS: Using data obtained from 1264 consecutive patients with prostate cancer treated with radical prostatectomy at four hospitals in Japan, biochemical recurrence-free survival rates were estimated and compared between the D'Amico, the National Institute for Health and Clinical Excellence, the Cancer of the Prostate Strategic Urological Research Endeavor, the National Comprehensive Cancer Network, and the European Society of Medical Oncology risk groups by using the Kaplan-Meier method and log-rank test. RESULTS: The 5-year biochemical recurrence-free survival rates in the D'Amico low-, intermediate-, and high-risk groups were 88.3%, 84.7% and 66.9%, respectively (low and intermediate risk vs high risk, P < 0.001). The 5-year biochemical recurrence-free survival rates in the National Institute for Health and Clinical Excellence, National Comprehensive Cancer Network, and European Society of Medical Oncology low-, intermediate- and high-risk groups were 88.3%, 84.3%, and 60.3%, respectively (low and intermediate risk vs high risk, P < 0.001). The 5-year biochemical recurrence-free survival rates in the Cancer of the Prostate Strategic Urological Research Endeavor low-, intermediate-, and high-risk groups were 90%, 83.5% and 60.3%, respectively (low and intermediate risk vs high risk, P < 0.001). Low- and intermediate-risk groups according to any of the risk stratification systems did not show significant differences in biochemical recurrence-free survival. CONCLUSION: Current risk stratification systems do not discriminate between low- and intermediate-risk groups in the Japanese population. A novel, pretreatment risk stratification system including other prognostic factors is necessary for an adequate prostate cancer risk assessment in the Japanese population. PMID- 25115633 TI - High plasma levels of HLA-G are associated with low birth weight and with an increased risk of malaria in infancy. AB - BACKGROUND: The immunosuppressive properties of HLA-G protein can create a tolerogenic environment that may allow Plasmodium falciparum to avoid host immune responses. There are known associations between high levels of circulating soluble HLA-G (sHLA-G) and either parasite or viral infections and it has been suggested that the induction of sHLA-G expression could be a mechanism via which infectious agents subvert host immune defence. The study presented here is the first to investigate the possible association between sHLA-G and malaria or malaria related risk factors in Benin. METHODS: A parasitological and clinical follow-up of 165 mothers and their newborns from delivery through to one year of age was conducted in the Tori Bossito area of southern Benin. Plasma levels of sHLA-G were determined by ELISA in maternal peripheral and cord blood and again in infants' peripheral blood at 3, 6, 9 and 12 months of age. The associations between the levels of sHLA-G and malaria risk factors were investigated through multivariate mixed models. RESULTS: Strong correlations were observed between the maternal and cord plasma concentrations of sHLA-G. In multivariate analyses, high cord plasma levels of sHLA-G were independently associated with (i) low birth weight and (ii) an increased risk of P. falciparum infection in infancy. CONCLUSION: These results show for the first time the possible involvement of sHLA-G in generating immune tolerance during pregnancy-associated malaria. Soluble HLA-G may represent a useful marker of susceptibility to malaria in infants and be associated with the higher susceptibility to infection observed for LBW children. PMID- 25115634 TI - Health related quality of life of children and adolescents with congenital adrenal hyperplasia in Brazil. AB - BACKGROUND: Congenital Adrenal Hyperplasia (CAH) is an endocrine disorder characterized by enzymatic deficiency in adrenal steroidogenesis, leading to adrenal insufficiency and hyperandrogenism. Patients need continuous hormone replacement therapy, but adequate control has proven challenging, exposing patients to undesirable consequences of both disease and treatment. OBJECTIVE: To evaluate the health related quality of life (HRQoL) of children and adolescents with CAH due to 21-hydroxylase deficiency. METHODS: In an analytical study, generic questionnaires, validated and translated versions, Pediatric Quality of Life Inventory 4.0 (for self-assessment of patients) and Child Health Questionnaire - PF50 (for parents) were applied and mean scores were analyzed with Student's t-test. RESULTS: We included 25 patients (19 female) with classical CAH (14 salt wasting/11 simple virilizing), mean age +/- standard deviation (SD) of 11.4 +/- 3.6 years (5-17.9), and their parents. Self-assessment of HRQOL showed decrease in mean scores: overall (67.8 +/- 15.5 vs. 88.9 +/- 7.4, p value = 0.015) and in the physical (75.2 +/- 15.0 vs. 95.9 +/- 5.8, p value = 0.014) and psychosocial (63.9 +/- 17.8 vs. 85.0 +/- 9.6, p value = 0.023) dimensions of patients, compared to healthy controls (previously published national data on children and adolescents). The assessment of the parent's view was concordant, also showing losses in the physical (43.7 +/- 8.0 vs. 55.1 +/- 3.6, p value = 0.013) and psychosocial (41.9 +/- 9.7 vs. 53.0 +/- 7.0, p value = 0.025) dimensions. The comparison of HRQOL between subgroups 1) males versus females and 2) salt-wasting versus simple virilizing showed no significant differences. CONCLUSION: There seems to be a loss of HRQOL in children and adolescents with classical CAH. The self-assessment was concordant in key areas with the assessment made by their parents. No differences were observed between genders or clinical presentation of the disease. PMID- 25115636 TI - The effect of anagliptin treatment on glucose metabolism and lipid metabolism, and oxidative stress in fasting and postprandial states using a test meal in Japanese men with type 2 diabetes. PMID- 25115635 TI - Effect of GLP-1 receptor agonists on waist circumference among type 2 diabetes patients: a systematic review and network meta-analysis. AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in patients with type 2 diabetes. However, the effect on abdominal obesity has not yet been confirmed. The study aimed to systematically evaluate the effect of GLP 1RAs on waist circumference in patients with type 2 diabetes. MEDLINE, EMBASE, the Cochrane library and www.clinicaltrialgov were searched through October 31, 2013. Randomized controlled trials with available data were selected if they compared GLP-1 RAs with placebo and traditional anti-diabetic drugs with a duration>=8 weeks. Weighted mean difference was estimated using random-effect model. Network meta-analysis was performed to supplement direct comparisons. Seventeen trials with 12 treatments were included. Overall, significant reductions on waist circumference following treatment of liraglutide--1.8 mg once daily (-5.24 cm, 95% CI -7.68, -2.93), liraglutide--1.2 mg once daily (-4.73 cm, 95% CI -6.68, -2.65) and exenatide--10 MUg twice daily (-1.34 cm, 95 % CI -2.00, 0.75) were detected versus placebo. The reduction effect was more evident when compared with insulin and thiazolidinediones (range -1.71 to -8.03 cm). Compared with exenatide, liraglutide--0.6 mg once daily, taspoglutide, liraglutide--1.2 mg once daily and liraglutide--1.8 mg once daily significantly decreased waist circumference from -3.32 to -6.01 cm. Besides, liraglutide--1.8 mg once daily significantly decreased waist circumference by -1.73 cm (95 % CI -3.04, -0.55) versus sitagliptin, whereas no significant difference following liraglutide--1.2 mg-once-daily treatment was detected compared with liraglutide--1.8 mg once daily and sitagliptin. Reduction was observed with statistical significance for exenatide--10 MUg twice daily compared with exenatide--5 MUg twice daily (-1.21 cm, 95% CI -2.43, -0.06). Ranking probability analysis indicated liraglutide--1.8 mg once daily and liraglutide--1.2 mg once daily decreased waist circumference most among all 12 treatments with probability of 98.36% and 91.82%, respectively. Some GLP-1RAs, especially liraglutide--1.8 mg once daily and liraglutide--1.2 mg once daily, were associated with a significant reduction in waist circumference. PMID- 25115637 TI - Comparison of salivary and calculated free cortisol levels during low and standard dose of ACTH stimulation tests in healthy volunteers. AB - Salivary cortisol (SC) has been increasingly used as a surrogate biomarker of free cortisol (FC) for the assessment of hypothalamo-pituitary-adrenal (HPA) axis, but there are not enough data regarding its use during ACTH stimulation tests. Therefore, we aimed to determine the responses of SC, calculated free cortisol (cFC) and free cortisol index (FCI) to ACTH stimulation tests in healthy adults. Forty-four healthy volunteers (24 men and 20 women) were included in the study. Low-dose (1 ug) and standard-dose (250 ug) ACTH stimulation tests were performed on two consecutive days. Basal and stimulated total cortisol (TC) and cortisol-binding globulin (CBG) levels and SC levels were measured during both doses of ACTH stimulation tests. cFC (by Coolens' equation) and FCI levels were calculated from simultaneously measured TC and CBG levels. The minimum SC, cFC, FCI levels after low-dose ACTH stimulation test were 0.21, 0.33, 16.06 ug/dL, and after standard-dose ACTH were 0.85, 0.46, 26.11 ug/dL, respectively, in healthy individuals who all had TC responses higher than 20 ug/dL. Peak CBG levels after both doses of ACTH stimulation tests were found to be higher in women than in men. So, by its effect, peak cFC and FCI levels were found to be lower in female than in male group. Neither TC nor SC levels were affected by gender. cFC and FCI levels depend on CBG levels and they are affected by gender. Cut-off levels for SC, cFC, FCI levels after both low- and standard-dose ACTH stimulation are presented. Studies including patients with adrenal insufficiency would be helpful to see the diagnostic value of these suggested cut-off levels. PMID- 25115642 TI - Detecting alcohol problems in older adults: can we do better? PMID- 25115643 TI - Mechanistic insights into the reduction of graphene oxide addressing its surfaces. AB - Both sides of a graphene oxide (ai-GO) layer are decorated with functional groups. For the first time it is demonstrated that an effective reduction of ai GO to graphene can be performed, even if the reducing agent can access only one side of ai-GO. A general reduction mechanism is proposed. PMID- 25115638 TI - PI3K/Akt/mTOR signaling in medullary thyroid cancer: a promising molecular target for cancer therapy. AB - The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a central hub for the regulation of cell proliferation, apoptosis, cell cycle, metabolism, and angiogenesis. Several studies have recently suggested that the PI3K/Akt/mTOR signaling pathway is implicated in the pathogenesis and progression of neuroendocrine tumors. Medullary thyroid cancer (MTC) is a neuroendocrine tumor developing from the C cells of the thyroid. Mutations in the RET proto-oncogene are involved in the pathogenesis of several forms of MTC. The deregulation of the PI3K/Akt/mTOR pathway seems to contribute to the tumorigenic activity of RET proto-oncogene mutations. Targeting this pathway through specific inhibitors at simple or multiple sites may represent an attractive potential therapeutic approach for patients with advanced MTCs. The aim of this review is to examine the role of the PI3K/Akt/mTOR pathway in the development and progression of MTC and the new therapeutic options that target this signaling pathway. PMID- 25115644 TI - Copper(II) catalyzed expeditious synthesis of furoquinoxalines through a one-pot three-component coupling strategy. AB - Microwave assisted one-pot transformation has been developed for the synthesis of biologically significant polysubstituted furoquinoxalines in good to excellent yields through a copper(II) catalyzed three-component coupling of o phenylenediamine, ethylglyoxalate, and terminal alkyne, known as A(3)-coupling, followed by 5-endo-dig cyclization. PMID- 25115646 TI - In vitro biological activities and fatty acid profiles of Pistacia terebinthus fruits and Pistacia khinjuk seeds. AB - This study reports in vitro anticholinesterase, antioxidant and antimicrobial effects of the n-hexane, dichloromethane, ethanol and ethanol-water extracts prepared from Pistacia terebinthus L. fruits and Pistacia khinjuk Stocks seeds as well as their total phenolic and flavonoid contents, and fatty acid compositions. Ethanol and ethanol-water extracts of both species exhibited higher anticholinesterase activity than galanthamine. Among ABTS, DPPH and CUPRAC assays, the highest antioxidant capacity of the extracts was found in the last one. P. terebinthus ethanol extract being rich in flavonoid content showed the best cupric reducing effect. All extracts possessed no antimicrobial activity. The main fatty acid in P. terebinthus fruits (52.52%) and P. khinjuk seeds (59.44%) was found to be oleic acid. Our results indicate that P. terebinthus fruits and P. khinjuk seeds could be a good source of anticholinesterase compounds, and could be phytochemically investigated. PMID- 25115645 TI - Oxidized multiwalled carbon nanotubes as antigen delivery system to promote superior CD8(+) T cell response and protection against cancer. AB - Properties like high interfacial area with cellular membranes, unique ability to incorporate multiple functionalization, as well as compatibility and transport in biological fluids make carbon nanotubes (CNTs) useful for a variety of therapeutic and drug-delivery applications. Here we used a totally synthetic hybrid supramolecule as an anticancer vaccine formulation. This complex structure comprises CNTs as delivery system for the Cancer Testis Antigen named NY-ESO-1, allied to a synthetic Toll-Like Receptor agonist. The CNT constructs were rapidly internalized into dendritic cells, both in vitro and in vivo, and served as an intracellular antigen depot. This property favored the induction of strong CD4(+) T as well as CD8(+) T cell-mediated immune responses against the NY-ESO-1. Importantly, the vaccination significantly delayed the tumor development and prolonged the mice survival, highlighting the potential application of CNTs as a vaccine delivery system to provide superior immunogenicity and strong protection against cancer. PMID- 25115647 TI - The effect of actual and imaginary handgrip on postural stability during different balance conditions. AB - The stabilizing effect of holding an object on upright posture has been demonstrated in a variety of settings. The mechanism of this effect is unknown but could be attributed to either additional sensorimotor activity triggered by a hand contact or cognitive efforts related to performance of a supra-postural task. A potential mechanism was investigated by comparing postural stability in young healthy individuals while gripping a custom instrumented wooden stick with a 5N force and while imagining holding the same stick in the hand. Twenty subjects were tested during three standing balance conditions: on a stationary surface, on a freely moving rockerboard, and with an unexpected perturbation of 10 degrees forward rockerboard tipping. Postural stability was evaluated as velocity of the center of mass (COM) and center of pressure (COP) compared across all experimental conditions. COM and COP velocities were equally reduced when subjects gripped the stick and imagined gripping while standing stationary and on the rockerboard. When perturbed, subjects failed to show any postural stability improvements regardless of handgrip task. Results indicate a stabilizing effect of focusing attention on motor task performance. This cognitive strategy does not appear to contribute any additional stabilization when subjects are perturbed. This study adds to the current understanding of postural stabilization strategies. PMID- 25115648 TI - In vivo investigations on luteotropic activity of prostaglandins during early diestrus in nonpregnant bitches. AB - The aim of this study was to test for the postulated luteotropic effect of prostaglandin E2 during early diestrus in the dog in an in vivo study. This study was performed on 30 bitches which were randomly assigned to a treatment group (TG) and a control group. Starting on the day of ovulation (Day 0), dogs of the TG were treated for 5, 10, 20, or 30 days with 10 mg firocoxib/kg body weight per day (Previcox, a selective PTGS2 inhibitor) and ovariohysterectomized for collection of corpora lutea on the last day of treatment. Similarly, dogs of the control group were ovariohysterectomized on Days 0, 5, 10, 20, and 30. Blood samples for progesterone measurement were collected every second day; additionally, the area of luteal cell nuclei and the expression of 3beta hydroxysteroid-dehydrogenase at the mRNA and the protein levels were assessed. Mean P4 concentrations were lower in TGs; however, a significant difference was only observed on Day 10. This observation is in line with the finding that treatment with firocoxib reduced expression of 3beta-hydroxysteroid-dehydrogenase mRNA and protein (P < 0.05) and the area of luteal cell nuclei (P < 0.05). The results of this study further point to the postulated luteotropic function of prostaglandin E2. PMID- 25115649 TI - (68)Ga based probe for Alzheimer's disease: synthesis and preclinical evaluation of homodimeric chalcone in beta-amyloid imaging. AB - In an attempt to explore use of PET radioisotope, (68)Ga, in the diagnosis of Alzheimer's disease, a metal-based homodimeric ligand exhibiting high affinity towards Abeta aggregates was designed by conjugating two chalcone units with the chelating system, diethylenetriaminepentaacetic acid. Bischalcone derivative, 5,8 bis(carboxymethyl)-13-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)-2-(2 (2-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)ethylamino)-2-oxoethyl)-10 oxo-2,5,8,11-tetraazatridecane-1-carboxylic acid, DT(Ch)2 was synthesized in 95% yield with high purity. It was radiolabelled with (68)Ga under mild conditions with 85.4% efficiency and 9.5-10 MBq nmol(-1) specific activity. An in vitro binding assay on Abeta42 aggregates displayed high binding affinity of (68)Ga DT(Ch)2 and inhibition constant of 4.18 +/- 0.62 nM. The fluorescent properties of the ligand with peaks of absorption/emission at 410/540 nm exhibited a blue shift with 5.5-fold increase in emission intensity on binding with Abeta aggregates. Blood kinetics of the complex performed on normal rabbit exhibited fast clearance (t1/2(F) = 24 +/- 0.08 min; t1/2(S) = 2 h 40 +/- 0.04 min). Ex vivo biodistribution analysis demonstrated blood-brain barrier penetration with brain uptake of 1.24 +/- 0.31% ID g(-1) at 2 min p.i. and rapid washout with negligible activity (0.36% ID g(-1)) left at 30 min p.i. These preliminary studies reveal that the bivalent approach of synthesis had minimal effect on binding affinity, signifying that the developed (68)Ga-complex, (68)Ga-DT(Ch)2, may offer a new perspective in generator produced PET imaging probes for Alzheimer's disease. PMID- 25115651 TI - Tracking anti-fibrotic pathways of nilotinib and imatinib in experimentally induced liver fibrosis: an insight. AB - The tyrosine kinase inhibitors imatinib and nilotinib have been suggested to have promising antifibrotic activity in experimental models of liver fibrosis. The aim of the present study was to investigate new pathways underlying this beneficial effect. Hepatic injury was induced in male Wistar rats by intraperitoneal injection of CCl4 for 12 weeks. During the last 8 weeks of treatment, rats were also injected daily intraperitoneally with 20 mg/kg imatinib or 20, 10 or 5 mg/kg nilotinib. At the end of treatment, effects on fibrosis were assessed by measuring serum fibrotic markers and profibrogenic cytokines, as well as by histopathological examination. Possible anti-inflammatory effects were estimated by measuring levels of inflammatory cytokines in liver tissue. Liver expression of alpha-smooth muscle actin, transforming growth factor (TGF)-beta1 antibodies and platelet-derived growth factor receptor beta (PDGFRbeta) was evaluated by immunohistochemical staining techniques. Nilotinib (5 and 10 mg/kg) significantly (P < 0.05) decreased all serum fibrotic markers measured, but 20 mg/kg of either nilotinib or imatinib had limited effects. At all doses tested, nilotinib significantly (P < 0.05) decreased the CCl4 -induced increases in tissue inflammatory cytokines. Furthermore, 5 and 10 mg/kg nilotinib significantly decreased TGF-beta1 levels and tissue expression of its antibody, as well expression of PDGFRbeta. In conclusion, low doses (5 and 10 but not 20 mg/kg) of nilotinib, rather than imatinib, can control hepatic fibrosis by regulating levels of proinflammatory cytokines, primarily interleukin (IL)-1 and IL-6. Nilotinib also controls the signalling pathways of profibrogenic cytokines by lowering TGF-beta1 levels and decreasing expression of PDGFRbeta. PMID- 25115652 TI - Liquid-based cytology in fine-needle aspiration of breast lesions: a review. AB - OBJECTIVE: Fine-needle aspiration (FNA) is a safe and cost-effective technique for the diagnosis of breast lesions, especially when correlated with clinical and imaging studies. However, the success of breast FNA is highly dependent on the adequate preparation of cytological conventional smears (CS). The liquid-based cytology (LBC) technique consists of an automated method for preparing thin-layer cytological samples from cell suspensions collected in alcohol-based preservative. LBC is designed to improve CS by avoiding limiting factors such as obscuring material, air-drying and smearing artifacts. STUDY DESIGN: We performed a review of the published literature about LBC applied to breast FNA. RESULTS: LBC preparations of breast aspirates demonstrated better cellular preservation, less cell overlapping and elimination of blood and excessive inflammation compared to CS. Conversely, alterations in architecture and cell morphology as well as loss of myoepithelial cells and stromal elements have been described in LBC specimens, requiring training before applying this technique for diagnosis. Studies have shown a similar accuracy between LBC and CS for the diagnosis of breast lesions. LBC also permits the use of residual material for ancillary tests, which is an important advantage compared to CS. CONCLUSIONS: LBC can be safely applied to breast FNA, showing a similar diagnostic accuracy to CS. PMID- 25115650 TI - Placental FKBP5 genetic and epigenetic variation is associated with infant neurobehavioral outcomes in the RICHS cohort. AB - Adverse maternal environments can lead to increased fetal exposure to maternal cortisol, which can cause infant neurobehavioral deficits. The placenta regulates fetal cortisol exposure and response, and placental DNA methylation can influence this function. FK506 binding protein (FKBP5) is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults. We hypothesized that placental FKBP5 methylation and genetic variation contribute to gene expression control, and are associated with infant neurodevelopmental outcomes assessed using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scales (NNNS). In 509 infants enrolled in the Rhode Island Child Health Study, placental FKBP5 methylation was measured at intron 7 using quantitative bisulfite pyrosequencing. Placental FKBP5 mRNA was measured in a subset of 61 infants by quantitative PCR, and the SNP rs1360780 was genotyped using a quantitative allelic discrimination assay. Relationships between methylation, expression and NNNS scores were examined using linear models adjusted for confounding variables, then logistic models were created to determine the influence of methylation on membership in high risk groups of infants. FKBP5 methylation was negatively associated with expression (P = 0.08, r = -0.22); infants with the TT genotype had higher expression than individuals with CC and CT genotypes (P = 0.06), and those with CC genotype displayed a negative relationship between methylation and expression (P = 0.06, r = -0.43). Infants in the highest quartile of FKBP5 methylation had increased risk of NNNS high arousal compared to infants in the lowest quartile (OR 2.22, CI 1.07-4.61). TT genotype infants had increased odds of high NNNS stress abstinence (OR 1.98, CI 0.92-4.26). Placental FKBP5 methylation reduces expression in a genotype specific fashion, and genetic variation supersedes this effect. These genetic and epigenetic differences in expression may alter the placenta's ability to modulate cortisol response and exposure, leading to altered neurobehavioral outcomes. PMID- 25115654 TI - Osteoinductive nanohydroxyapatite bone substitute prepared via in situ hydrothermal transformation of cuttlefish bone. AB - The capacity to induce a rapid and controlled healing of bone defects is critical for a bone substitute. Previous studies have reported hydrothermal transformation (HT) of aragonite from cuttlebone (CB) to cuttlebone hydroxyapatite (CBHA). However, the biocompatibility and in vivo characteristic of CBHA have not been fully investigated. We fabricated CBHA via the in situ HT of aragonite from CB. This CBHA exhibited a highly porous structure and nanoscaled surface morphology with a significantly higher protein adsorption rate than CB. Marrow mesenchymal stem cells (MSCs) were seeded and cultured on the CBHA and CB to evaluate their influence on cell proliferation and differentiation. According to scanning electronic microscopy observation and MTT assay, the MSCs adhered and proliferated well on both the CBHA and CB. Compared with the cells on the CB, the MSCs on CBHA exhibited enhanced alkaline phosphatase activity and osteocalcin levels after 13 days of culture. In vivo testing revealed that CBHA could induce ectopic bone formation after implantation, while no bone formation being observed in the CB. These findings demonstrated that a nanoscaled and osteoinductive bone substitute could be produced by hydrothermally transforming an aragonite of CB into a hydroxyapatite. PMID- 25115655 TI - Trochlear boss height measurement: a comparison of radiographs and MRI. AB - BACKGROUND: A key anatomical consideration and determinant of surgical approach in trochlear dysplasia is the trochlear boss height (TBH), traditionally defined by measurements on plain X-rays (XR). Magnetic resonance (MR) imaging is increasingly used for pre-operative planning and follow-up. However, it is unclear whether measurement of TBH on XR is applicable to MR. The aim of this study was to establish the reliability of TBH measurement on MR compared to XR. METHODS: This study used lateral knee radiographs and MR scans of 14 knees of patients with trochlear dysplasia, six knees of non-dysplastic patients with anterior knee pain (AKP), and five knees of non-dysplastic controls with no AKP. Correlation between XR and MR measurements was assessed using Pearson correlation coefficients. Agreement between methods and observers was assessed using Bland Altman plots with 95% limits of agreement. Intra- and inter-observer reliability was assessed using intraclass correlation coefficients (ICC). RESULTS: Bland Altman charts showed a total width of 95% limits of agreement of 4.78 mm for XR and MR subchondral bone (SB) TBH measurements, and 6.73 mm for XR and MR cartilage TBH measurements. Inter-observer ICCs were 0.86 for XR, 0.62 for MR SB, and 0.53 for MR cartilage. The widths of the Bland-Altman 95% limits of agreement between observers were 4.79 mm (XR), 5.04 mm (MR SB) and 4.74 mm (MR cartilage). CONCLUSION: Measurement of TBH on MR is not directly interchangeable with XR. Adjustments need to be made to treatment thresholds based on XR measurement if MR is used instead. PMID- 25115656 TI - Root avulsion of the posterior horn of the medial meniscus in skeletally immature patients. AB - BACKGROUND: Meniscal root avulsion has been predominantly reported in an adult population but little is known about this meniscal lesion in children and adolescents. PURPOSE: The of this article is to describe the clinical symptoms and a new MRI sign of a medial meniscus posterior root avulsion in skeletally immature patients, and to report the arthroscopic procedure for its reinsertion in the presence of open physes. CASE DESCRIPTION: We report two skeletally immature patients who had a medial meniscus posterior root avulsion [MMPRA]. Diagnosis of a MMPRA was suspected on MRI by intense T2 hypersignal located at the postero-medial part of the tibial plateau reflecting trabecular bone oedema ("Bone bruise") at the level of the medial meniscal posterior root attachment. Arthroscopic reduction and fixation of the posterior root of the medial meniscus with transosseous sutures was performed. The patients returned to sport at the end of 6 months without residual symptoms. At one year, the radiographs showed no modification of the physis. Healing of the medial meniscal posterior root was noted on MRI. CLINICAL RELEVANCE: In a skeletally immature patient it is important that this rare meniscal lesion is diagnosed early and adequately treated. We emphasize the importance of the indirect MRI signs that can lead a clinician to suspect the diagnosis of MMPRA. The aim of the surgery was to restore the anatomical footprint of the meniscal root and to re-establish its function thus preventing future chondral damage without damage to the tibial physeal growth plate. LEVEL OF EVIDENCE: Level IV. PMID- 25115657 TI - Subclinical hypothyroidism: to treat or not to treat? PMID- 25115658 TI - Improvement of complex regional pain syndrome after plasmapheresis. AB - Complex regional pain syndrome is a severe complication following trauma that is associated with vasomotor, sudomotor and sensory disturbances in an affected limb or region of the body. The exact physiopathology is not fully understood yet. Recently, autoantibody findings suggested an immune-mediated physiopathology of the disease. We here describe two otherwise treatment-resistant patients with complex regional pain syndrome and high-titre beta2 adrenergic receptor autoantibodies, who did respond to plasmapheresis. Both patients showed strong improvement of pain and autonomic symptoms measured by impairment level sum score. PMID- 25115659 TI - Histologic evaluation of human pulp tissue after orthodontic intrusion. AB - INTRODUCTION: The forces applied during orthodontic treatment bring about effects on the teeth and surrounding tissues. The aim of this study was to evaluate the possible changes in the human pulpal tissue resulting from orthodontic intrusion in a 21-day period using histologic examination. METHODS: The sample consisted of 17 young individuals of both sexes between the ages of 12 and 19 years. A total of 34 premolars were evaluated with orthodontic indication of extraction. Because it is a split-mouth study, in each patient, intrusion force of 60 g was applied randomly on 1 of the dental elements experimental group for 21 days. The counterpart control group received no force. After extractions, these dental elements were fixed in 10% formaldehyde, processed automatically, submitted to histotechnical preparation, and stained with hematoxylin-eosin for analysis under optical microscope. RESULTS: The paired Fisher exact test (P <= .05) showed a significant increase of fibrous tissue in the experimental group. The nonparametric paired Wilcoxon test (P <= .05) showed a significant increase in the number of pulpal nodules in the elements of the experimental group and showed no difference in the number of blood vessels between the groups. Large-caliber vessels and congested elements were observed in 8 of the experimental group elements. CONCLUSIONS: The orthodontic intrusion force, in these conditions, caused vascular changes in the pulpal tissue and also increased the presence of fibrosis and the number of pulp calcifications in the experimental elements. PMID- 25115660 TI - Sealers and warm gutta-percha obturation techniques. AB - INTRODUCTION: Warm vertically compacted gutta-percha obturation techniques use root canal sealers that are heated during the obturation. This study aims at investigating the suitability of selected sealers with warm gutta-percha obturation techniques. METHODS: The composition of an experimental sealer (Septodont; Saint Maur-des-Fosses, France), MTA Fillapex (Angelus, Londrina, Brazil), Apexit Plus (Ivoclar, Schaan, Lichtenstein), and AH Plus (Dentsply International, Addlestone, UK) was assessed by scanning electron microscopic and energy-dispersive spectroscopic analysis. The effect of temperature during warm vertical compaction technique was investigated by testing the sealers' properties after 1 minute to 100 degrees C or 37 degrees C. The reaction products after setting were assessed by X-ray diffraction analysis and Fourier transform infrared spectroscopy. Changes in setting time, flow, and film thickness were determined using ISO 6876 (2012) specifications. RESULTS: The experimental tricalcium silicate-based sealer and Apexit Plus contained calcium hydroxide peaks after setting, which were absent in MTA Fillapex. The properties of AH Plus and the experimental sealer were modified by heat; the setting time was reduced, and film thickness increased. AH Plus had diminished N-H groups when heated to 100 degrees C for 1 minute. MTA Fillapex, Septodont sealer, and Apexit Plus were unaffected by heat application. CONCLUSIONS: The choice of sealer should be considered when selecting the obturation technique. The Septodont sealer is recommended for obturations using cold laterally condensed gutta-percha, whereas MTA Fillapex and Apexit Plus were suitable with warm gutta-percha obturation techniques. PMID- 25115661 TI - Unusual morphology of permanent tooth related to traumatic injury: a case report. AB - INTRODUCTION: Root duplication, or multiple roots, is a very rare anatomy of the maxillary central incisor. METHODS: This case report describes a permanent central incisor having 2 distinct roots as an assumed sequela of the avulsion and replantation of a primary incisor. RESULTS: The permanent successor might have had a disturbance of development because of the traumatic injury and discontinuity in the treatment after replantation. Conventional endodontic treatment followed by esthetic restoration was performed on the tooth. CONCLUSIONS: Clinicians should consider the potential prognoses and complications of traumatic injuries to primary teeth. PMID- 25115662 TI - [Advances in the use of instrumental measurement of colour in the development, production and quality control of drugs, medicinal preparations and pharmaceutical auxiliary substances II*]. AB - The paper summarizes the use of instrumental colour measurement in the field of pharmaceuticals of natural origin and other substances of natural origin beneficial for health in recent 10 years. Colour measurement in this field was most frequently employed in the monitoring of various aspects of the process of drying of medicinal plants and their parts. PMID- 25115663 TI - [Preparation and evaluation of the oral gel containing the essential oil from Siberian fir (Abies sibirica Ledeb.)]. AB - Essential oil of the Siberian fir (Abies sibirica Ledeb.) ranks among the substances with potential use in prevention and treatment of oral candidiasis. Therefore, the aim of the study was the formulation, preparation and evaluation of an oral gel containing 0.3% of this essential oil. Carbopol 974P NF in 1% concentration was used as the gelling agent, some samples were additionally stabilized by an addition of polysorbate 80 (0.1-0.5%). Xylitol in concentrations of 10% or 20% was added with the aim to modify the taste properties of the gel. Following microscopic evaluation (mean oil droplet size, degree of dispersity) immediately after preparation and after 6-month storage, it has been found that the optimal concentration of polysorbate 80 is 0.3%. The results of the experiment also demonstrated that xylitol was not only an excipient adjusting the organoleptic properties of the preparation - its use enabled significant improvement of the quality parameters and stability. PMID- 25115664 TI - [Flavonoids - main constituents of the leaves of Philadelphus tenuifolius Rupr. et Maxim]. AB - The paper deals with the isolation and identification of the constituents of the leaves of Philadelphus tenuifolius Rupr. et Maxim. A methanolic extract was used to isolate quercetin-3-O-glucoside (isoquercitrin), and a butanolic extract to isolate kaempferol-3-O-glucoside-7-O-rhamnoside. Isolates were identified by physical-chemical data, comparison with authentic samples and literature data. The above-mentioned compounds were isolated from Philadelphus tenuifolius Rupr. et Maxim. for the first time. PMID- 25115665 TI - [Formulation of benzethonium chloride into gels]. AB - This study is focused on the preparation of gels with antimicrobial effects. A quaternary ammonium salt, benzethonium chloride, in a concentration of 0.01-0.5% (w/w) was employed as the drug. The humectant employed was propylene glycol in concentrations of 5% and 10% (w/w). Two types of polymers, chitosan and hydroxyethyl cellulose, in the same concentrations of 2.5% (w/w), were used for gel preparation. Finally the flow properties, rheological parameters and pH values of the gels were evaluated. Based on the obtained results, the samples of the gels prepared on the basis of chitosan and hydroxyethyl cellulose, which have the following optimum composition shown below, were found: 2,5% (w/w) CHIT + 0,5% (w/w) BZCl + 10% (w/w) PG; 2,5% (w/w) HEC + 0,5% (w/w) BZCl + 5% (w/w) PG. PMID- 25115666 TI - [Impact of formulation and process parameters on the properties of chitosan-based microspheres prepared by external ionic gelation]. AB - The aim of this experimental study was to optimize a preparation of microspheres from high viscosity chitosan by external ion gelation and to evaluate selected aspects of their preparation. For drug-free microparticles, the concentration of chitosan dispersions was chosen as a formulation variable; the position of instrument for a dispersion extrusion (horizontal vs. vertical) was evaluated as a process variable. On the basis of sphericity and equivalent diameter results, three different concentrations of chitosan dispersions were used for 5 aminosalicylic acid (5-ASA) encapsulation with the extrusion instrument in horizontal position, which was considered as the optimal. In consequent drug loaded microparticle preparation, the influence of the concentration of chitosan dispersions and composition of hardening solution (10% sodium tripolyphosphate (TPP) vs. 10% TPP containing drug) was evaluated. In prepared 5-ASA microspheres it was found that the equivalent diameter increased with increasing chitosan concentration. In the case of sphericity, significant differences were not found. Samples prepared with the drug in both chitosan dispersion and hardening solution had a higher drug content, a smaller equivalent diameter and they showed a faster in vitro drug release in comparison with the samples prepared with the drug in chitosan dispersion only. PMID- 25115667 TI - [Alois Jandouss Czech pharmacopoeial terminology of 1864]. AB - PhMr. Alois Jandous (1838-1893), a Prague pharmacist, laid the foundations of modern Czech pharmaceutical literature. His first Czech book was a Latin-Czech dictionary published in 1864. Jandous collected the terms from the 5th edition of the Austrian Pharmacopoeia. Besides Czech translations of nine hundred Latin names of pharmaceuticals, it also presented many Czech synonyms and translations of other technical terms. Though not all of his proposed terms have been accepted, he has established modern Czech pharmaceutical terminology. PMID- 25115668 TI - [Rationalization in 20th-century Czechoslovak pharmacy practice - commission for rationalization and standardization in medicine, veterinary medicine and pharmacy - part 1]. AB - In the 1920s Czechoslovakia, an increased attention was paid to the new ideas of scientific management (Taylorism), work rationalization and standardization. This was reflected in the foundation of the Masaryk Academy of Work in 1920. An effort to implement the new principles into health care led to the establishment of the Commission for Rationalization and Standardization in Medicine, Veterinary Medicine and Pharmacy (RANOK) within the Department of Natural Science and Medicine of the Academy. Within RANOK, the group for pharmacy worked between 1928 1932. The first part of the paper describes the scientific management and standardization movement in interwar Czechoslovakia, and the establishment of Masaryk Academy of Work and RANOK, including the group for pharmacy. The paper discusses the work objectives of the commission and presents concise biographies of the group for pharmacy members, too. The second part will be focused on the work results, relative failure and role of the group. KEYWORDS: Masaryk Academy of Work Comission for Rationalization and Standardization in Medicine Veterinary Medicine and Pharmacy (RANOK) work rationalization standardization pharmacy practice. PMID- 25115669 TI - Pulmonary embolism in burns, is there an evidence based prophylactic recommendation? Case report and review of literature. AB - Burn patients exhibit an acquired hypercoagulable state with increased risk of venous thromboembolism. Currently, no randomized control study assessing the efficacy of chemical venous thromboembolism (VTE) prophylaxis in burn patients has been performed. We present a case of a morbidly (body mass index>54kg/m(2)) obese patient with 18% total body surface area (TBSA) burn who developed a VTE and a non-fatal submassive pulmonary embolus (PE). We will be reviewing the current consensus of venous thrombosis prophylaxis in burn patients and briefly discuss the treatment of PE in this population. PMID- 25115670 TI - "Banding" esophagus: circumferential bruising due to ligature neck constriction or circumferential hypostasis due to rapid death? PMID- 25115671 TI - The applicability of using different energy levels in CT imaging for differentiation or identification of dental restorative materials. AB - PURPOSE: The goal of this study was to investigate whether different computed tomography (CT) energy levels could supply additional information for the differentiation of dental materials for forensic investigations. METHODS: Nine different commonly used restorative dental materials were investigated in this study. A total of 75 human third molars were filled with the restorative dental materials and then scanned using the forensic reference phantom in singlesource mode. The mean Hounsfield unit values and standard deviations (SDs) of each material were calculated at 120, 80 and 140 kVp. RESULTS: Most of the dental materials could be differentiated at 120 kVp. We found that greater X-ray density of a material resulted in higher SDs and that the material volume could influence the measurements. CONCLUSION: Differentiation of dental materials in CT was possible in many cases using single-energy CT scans at 120 kVp. Because of the number of dental restorative materials available and scanner and scan parameter dependence, as well as the CT imaging artifacts, the identification (in contrast to differentiation) was problematic. PMID- 25115672 TI - Postmortem wounds caused by cookie-cutter sharks (Isistius species): an autopsy case of a drowning victim. PMID- 25115673 TI - Overlaying, co-sleeping, suffocation, and sudden infant death syndrome: the elephant in the room. PMID- 25115674 TI - Urinary reconstruction in vertebral, anorectal, cardiac, trachea-esophageal, renal abnormalities and limb defects association with chronic renal failure and penile duplication. AB - Various urological complications in VATER association require careful management. A 15-year-old boy with VATER association, including a hypoplastic lower urinary tract and diphallia, presented with chronic kidney disease and incontinence after a right loop ureterostomy. In order to acquire urinary continence without renal function impairment, an ileocecal reservoir with umbilical catheterizable stoma was created as a urinary reconstruction. The ectopic posterior penis was resected for cosmetic reasons, and the stump of the hypoplastic urethra was opened at the perineal skin. Clean intermittent self-catheterization through the umbilicus using disabled bilateral limbs was then achieved. This report describes the management of VATER association in a patient with complicated urological anomalies. PMID- 25115675 TI - Immunization against a merozoite sheddase promotes multiple invasion of red blood cells and attenuates Plasmodium infection in mice. AB - BACKGROUND: Subtilisin-like protease 2 (SUB2) is a conserved serine protease utilized by Plasmodium parasites as a surface sheddase required for successful merozoite invasion of host red blood cells and has been implicated in ookinete invasion of the mosquito midgut. To determine if SUB2 is a suitable vaccine target to interfere with malaria parasite development, the effects of SUB2 immunization on the Plasmodium life cycle were examined in its vertebrate and invertebrate hosts. METHODS: Swiss Webster mice were immunized with SUB2 peptides conjugated to Keyhole limpet hemocyanin (KLH) or KLH alone, and then challenged with Plasmodium berghei. To determine the effects of immunization on parasite development, infected mice were evaluated by blood film and Giemsa staining. In addition, collected immune sera were used to perform passive immunization experiments in non-immunized, P. berghei-infected mice to determine the potential role of SUB2 in parasite development in the mosquito. RESULTS: Following P. berghei challenge, SUB2-immunized mice develop a lower parasitaemia and show improved survival when compared to control immunized mice. Moreover, SUB2 immunization results in an increase in the number of multiply invaded red blood cells, suggesting that SUB2 antibodies interfere with merozoite invasion. Passive immunization experiments imply that SUB2 may not have a major role in ookinete invasion, but this requires further investigation. CONCLUSION: By interfering with red blood cell invasion, immunization against SUB2 limits malaria parasite development and confers protection from severe malaria. Together, these results provide proof-of-principle evidence for future investigation into the use of SUB2 as a vaccine or drug target to interrupt parasite development in more relevant human malaria models. PMID- 25115677 TI - Mitochondrial DNA sequence of Lampetra morri. AB - Lampetra morri belongs to the Petromyzontidae family. It is one of the most important freshwater aquaculture species in China. In this study, the complete sequence of mitochondrial genome of L. morri was 16,451 base pair, including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 2 repeat regions. The percentage of G + C content was 39.33%. This is the first time of the mitochondrial genome of L. morri being sequenced, and it provides insights into the evolution of Cyclostomata mitochondrial genomes, particular in Lampetra family. PMID- 25115678 TI - The complete mitochondrial genome of Saurida umeyoshii (Aulopiformes: Synodontidae). AB - In this study, the complete mitochondrial genome (mitogenome) sequence of Saurida umeyoshii has been determined by long polymerase chain reaction and primer walking methods. The complete mitochondrial genome is 16,546 bp in length and contains 37 mitochondrial genes (13 protein-coding genes, 2 ribosomal RNA (rRNA), 22 transfer RNA (tRNA)), and a control region as other bony fishes. Within the control region, we identified the termination-associated sequence domain (TAS), the central conserved sequence block domains (CSB-F, CSB-E, CSB-D, CSB-C, CSB-B and CSB-A), and the conserved sequence block domains (CSB-1, CSB-2 and CSB-3). PMID- 25115676 TI - Single-walled carbon nanotubes alleviate autophagic/lysosomal defects in primary glia from a mouse model of Alzheimer's disease. AB - Defective autophagy in Alzheimer's disease (AD) promotes disease progression in diverse ways. Here, we demonstrate impaired autophagy flux in primary glial cells derived from CRND8 mice that overexpress mutant amyloid precursor protein (APP). Functionalized single-walled carbon nanotubes (SWNT) restored normal autophagy by reversing abnormal activation of mTOR signaling and deficits in lysosomal proteolysis, thereby facilitating elimination of autophagic substrates. These findings suggest SWNT as a novel neuroprotective approach to AD therapy. PMID- 25115683 TI - Trends in prevalence and treatment of ocular allergy. AB - PURPOSE OF REVIEW: This review describes recent findings and trends in prevalence and treatment of allergic ocular diseases. Although the major focus is on seasonal and perennial allergic conjunctivitis, related disorders will also be considered. RECENT FINDINGS: Published reports from countries around the world suggest that the spectrum of atopic diseases, including seasonal and perennial allergic conjunctivitis, is continuing its pattern of increasing prevalence, which has been well documented over the past few decades. In addition, although treatment modalities have focused on topical formulations including antihistamines and corticosteroids, there is a significant emphasis on immunotherapy as an alternative treatment modality, particularly in the USA. SUMMARY: Allergic conjunctivitis is a key component in the spectrum of allergic diseases that is sometimes collectively referred to as rhinoconjunctivitis. Because of its high prevalence worldwide, it exacts an increasing toll in terms of patient discomfort, morbidity, and loss of productivity. Current estimates suggest that at least 20% of the overall population suffers from some form of allergic conjunctivitis, many without ever seeking treatments. In addition, a significant proportion of patients experience chronic forms of allergy that are less responsive to existing therapies. Recent approval of immunotherapy-based treatments may address this therapeutic gap. PMID- 25115684 TI - Update on house dust mite immunotherapy: are more studies needed? AB - PURPOSE OF REVIEW: Although systematic reviews have confirmed the effectiveness of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for the treatment of allergic rhinitis and allergic asthma, a review of studies employing extracts of house dust mites (HDMs) for immunotherapy found no consensus on basic treatment parameters. RECENT FINDINGS: Over the last 2 years nine additional reports on immunotherapy with HDM extract preparations have been published. Six studies were with SLIT, five for allergic rhinitis and one for allergic asthma. The other three studies were all with SCIT in children with allergic asthma. SUMMARY: The publication of these nine studies supports the efficacy of HDM-SLIT for allergic rhinitis and asthma and for HDM-SCIT for asthma in children. The reported safety data are also reassuring, especially for SLIT.HDM-SLIT tablets under development will have optimal doses established in large, randomized, placebo-controlled trials. The HDM-SCIT trial in children with allergic asthma confirms the efficacy of a commercialized HDM preparation for injection immunotherapy. However, the information that is presented on dosing in the articles on SLIT-liquid is unsatisfactory, as doses are not presented in a form that the clinician can use to guide their practice. PMID- 25115682 TI - Type-2 innate lymphoid cells in human allergic disease. AB - PURPOSE OF REVIEW: Recent decades have seen allergic diseases become endemic in a number of developed countries. Understanding the inflammatory processes that dictate these allergic responses is therefore important. RECENT FINDINGS: Critical to many allergic responses is the inappropriate release of the type-2 immune-regulatory cytokines: interleukin-4, interleukin-5, interleukin-9, and interleukin-13. The study of these inflammatory mediators has led directly to the development of two new asthma treatments: anti-interleukin-5 and anti-interleukin 13. Until recently, T helper 2 cells were considered to be the major cellular source of type-2 cytokines; however, a paradigm shift occurred with the discovery of a novel population, type-2 innate lymphoid cells (ILC2s), that can produce huge levels of type-2 cytokines and are sufficient to induce allergy in mice. This discovery raises interesting questions about how innate and adaptive type-2 immunity might interact to induce relapsing and remitting episodes of allergy in patients. SUMMARY: It is essential that alongside the mechanistic investigation using model organisms, the roles of ILC2s in human disease be explored. Here, we discuss how ILC2 traits, discovered in mouse models, have informed research in humans and how newly identified human ILC2 pathways might provide potential therapeutic benefits in the future. PMID- 25115685 TI - Specific immunotherapy and biological treatments for occupational allergy. AB - PURPOSE OF REVIEW: Occupational allergy represents a substantial health, social, and financial burden for the society. Its management is a complex task that, in selected cases, may also include allergen-specific immunotherapy. The purpose of this article is to review clinical data on allergen immunotherapy and biological treatments applied to occupational allergy in 2013. RECENT FINDINGS: Immunotherapy in occupational allergic diseases has been scarcely used, and only for a few sensitizers, such as latex, flour, and Hymenoptera venom, partly due to the lack of standardized extracts. The recent use of the molecular diagnosis can improve the indication and selection of suitable allergens for preparing new standardized and powerful extracts for immunotherapy. Some recent reports suggest a beneficial role of treatment with omalizumab in workers with occupational asthma who continue to be exposed to the causal agent. SUMMARY: Although scarce, available data suggest that immunotherapy and biological treatments may allow allergic workers to continue their work activity, but further studies are needed to standardize extracts and to evaluate the cost-effectiveness of these treatments, when exposure at the workplace cannot be avoided. PMID- 25115687 TI - Supercritical CO2 extraction of volatile oils from Sardinian Foeniculum vulgare ssp. vulgare (Apiaceae): chemical composition and biological activity. AB - This article reports the results on the composition and antifungal effect of volatile extracts obtained from the aerial parts of Sardinian wild fennel (Foeniculum vulgare Mill.), by supercritical fluid extraction (SFE) and by hydrodistillation (HD). The extracts were analysed by gas chromatography-mass spectrometry for qualitative composition and gas chromatography-flame ionisation detector to establish the percentage of constituents. The main components were fenchone (7.1% vs. 8.8%), estragole (34.9% vs. 42.6%) and (E)-anethole (24.6% vs. 43.4%) in the SFE and HD extract, respectively. Minimum inhibitory concentrations (MICs) were measured according to the reference Clinical and Laboratory Standards Institute (CLSI) broth macrodilution protocols. Minimum lethal concentrations were determined by subsequent subculturing of the same cell suspensions in solid medium. The essential oil was more active against Candida albicans, whereas the supercritical fluid extract possesses higher activity against Candida guillermondii and Cryptococcus neoformans, with MIC values of 0.32 MUL/mL. PMID- 25115686 TI - A pilot clinical study of resveratrol in postmenopausal women with high body mass index: effects on systemic sex steroid hormones. AB - BACKGROUND: Breast cancer risk is partially determined by several hormone-related factors. Preclinical and clinical studies suggested that resveratrol may modulate these hormonal factors. METHODS: We conducted a pilot study in postmenopausal women with high body mass index (BMI >= 25 kg/m2) to determine the clinical effect of resveratrol on systemic sex steroid hormones. Forty subjects initiated the resveratrol intervention (1 gm daily for 12 weeks) with six withdrawn early due to adverse events (AEs). Thirty-four subjects completed the intervention. RESULTS: Resveratrol intervention did not result in significant changes in serum concentrations of estradiol, estrone, and testosterone but led to an average of 10% increase in the concentrations of sex steroid hormone binding globulin (SHBG). Resveratrol intervention resulted in an average of 73% increase in urinary 2-hydroxyestrone (2-OHE1) levels leading to a favorable change in urinary 2-OHE1/16alpha-OHE1 ratio. One participant had asymptomatic Grade 4 elevation of liver enzymes at the end of study intervention. Two subjects had Grade 3 skin rashes. The remaining adverse events were Grade 1 or 2 events. The most common adverse events were diarrhea and increased total cholesterol, reported in 30% and 27.5% of the subjects, respectively. CONCLUSION: We conclude that among overweight and obese postmenopausal women, daily 1 gm dose of resveratrol has favorable effects on estrogen metabolism and SHBG. Further placebo-controlled studies are needed to confirm our findings on these hormone-related breast cancer risk factors and the attribution of the adverse effects observed in the study population. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01370889. PMID- 25115689 TI - Is it possible to predict urodynamic stress urinary incontinence in women with minimal diagnostic evaluation? AB - OBJECTIVES: To determine whether it is possible to predict urodynamic stress urinary incontinence (uSUI) in women with minimal diagnostic evaluation. MATERIALS AND METHODS: Medical records of 2,643 female incontinent patients were reviewed and 301 women were eligible for this study. The positive predictive values (PPV), sensitivity, specificity and negative predictive values (NPV) for uSUI and uSUI with or without detrusor overactivity (DO), and DO patients of pure SUI symptom (group 1), combination of pure SUI symptom and positive provocative stress test (+PST; group 2) and combination of pure SUI symptom, +PST and absence of overactive bladder symptoms (group 3) were calculated for each group. RESULTS: Mean age was 51.03 years (22-88). PPV, sensitivity and specificity values for uSUI with or without DO of group 3 were 100, 7.4, and 100%, while these values for pure uSUI were 93.3, 9.3, and 99.3%, respectively. Interestingly, none of the patients in groups 2 and 3 had DO. CONCLUSIONS: Our results show that it was possible to predict uSUI with high accuracy using minimal diagnostic evaluation in a group of female patients with pure stress incontinence symptoms +PST while it was also possible to eliminate DO accurately in this group of patients. PMID- 25115688 TI - Predictors of hoarding severity in older adults with hoarding disorder. AB - BACKGROUND: The recent addition of hoarding disorder (HD) to the Diagnostic and Statistical Manual of Mental Health Disorders, 5th edition, has highlighted the dearth of information about the demographic, sociologic, and medical predictors of HD severity, particularly in older adults. Although there have been several previous studies examining the characteristics of older adults with HD, and one investigation of psychiatric correlates of hoarding symptom severity in non clinical older adults, there has been little investigation about which characteristics predict hoarding symptom severity in older adults with HD. METHODS: Participants were 71 older adults who were enrolled for one of the two studies of HD at the VA San Diego Healthcare System between January 2010 and January 2014. RESULTS: There were multiple differences in the predictive ability of patient characteristics between the more cognition-related symptoms of HD and the more concrete measure of clutter, including gender-based differences and anxiety severity. Further, married participants were more likely to report lower hoarding severity, and there was no significant relationship between hoarding severity and intervention attempts or hoarding and reported falls in the past three years. CONCLUSIONS: Multiple predictive factors have been presented, which may result in further studies to investigate possible predictive differences in cognition and clutter symptoms of HD. Future studies should examine the possibility of the predictive factors also identified to be moderators of treatment outcomes. PMID- 25115690 TI - Electron-phonon coupling in quantum-well states of the Pb/Si(1 1 1) system. AB - The electron-phonon coupling parameters in the vicinity of the Gamma point, lambda(Gamma), for electronic quantum well states in epitaxial lead films on a Si(1 1 1) substrate are measured using 5, 7 and 12 ML films and femtosecond laser photoemission spectroscopy. The lambda (Gamma) values in the range of 0.6-0.9 were obtained by temperature-dependent line width analysis of occupied quantum well states and found to be considerably smaller than the momentum averaged electron-phonon coupling at the Fermi level of bulk lead, (lambda = 1.1-1.7). The results are compared to density functional theory calculations of the lead films with and without interfacial stress. It is shown that the discrepancy can not be explained by means of confinement effects or simple structural modifications of the Pb films and, thus, is attributed to the influence of the substrate on the Pb electronic and vibrational structures. PMID- 25115691 TI - Selection of proper reference genes for the cyanobacterium Synechococcus PCC 7002 using real-time quantitative PCR. AB - Synechococcus sp. PCC 7002 is known to be tolerant to most of the environmental factors in natural habitats of Cyanobacteria. Gene expression can be easily studied in this cyanobacterium, as its complete genome sequence is available. These properties make Synechococcus sp. PCC 7002 an appropriate model organism for biotechnological applications. To study the gene expression in Cyanobacteria, real-time quantitative PCR (qPCR) can be used, but as this is a highly sensitive method, data standardization is indicated between samples. The most commonly used strategy is normalization against internal reference genes. Synechococcus sp. PCC 7002 has not yet been evaluated for the best reference genes. In this work, six candidate genes were analyzed for this purpose. Cyanobacterial cultures were exposed to several stress conditions, and three different algorithms were used for ranking the reference genes: geNorm, NormFinder, and BestKeeper. Moreover, gene expression stability value M and single-control normalization error E were calculated. Our data provided a list of reference genes that can be used in qPCR experiments in Synechococcus sp. PCC 7002. PMID- 25115695 TI - Adrenoceptor Polymorphisms in Hypertension and Diabetes with obesity-update in 2014. AB - Hypertension, diabetes mellitus (especially type 2 diabetes mellitus) and metabolic syndrome associated with obesity are rapidly growing public health problems. Sympathetic nerve activation is well documented in hypertension, diabetes mellitus, and obesity, hypertension and diabetes are determined by genetic background and environmental factors. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of sympathetic nervous system in obesity have been mainly mediated via the beta2 and beta3-adrenergic receptors in humans. Further, beta2 adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. Genetic polymorphisms of the ?-adrenoceptor gene have been shown to alter the function of several adrenoceptor subtype and thus to modify the response to catecholamine. Among beta2-adrenoceptor polymorphisms, Arg16Gly, Gln27Glu, and Thr164Ile are considered the most functionally important. beta2 adrenoceptor genes have been studied in relation to hypertension. Genetic variations in the beta3-adrenoceptor, such as the Try64Arg variant, are also associated with both obesity and hypertension. This review is an update of several versions published of the relationships between adrenoceptor polymorphisms and hypertension, diabetes and obesiy based on the my own review on the relationship with obesity in 2011 in "Journal of Obesity" [1], and another of my own reviews on the relationships with hypertension in 2010 in "International journal of Hypertension" [2], with 37 articles provided by the "PubMed" with the keywords of "adrenoceptor polymorphisms, obesity, hypertension and diabetes" searched on December 2013. However, the relationships of the polymorphisms of beta2- and beta3-adrenoceptor genes with sympathetic nervous system activity, hypertension and metabolic syndrome have been still discordant, it might be related to the ethnicity, gender, severeity of obesity, duration of hypertension or obesity, etc (refer the "Possible confounding variable affecting the relationships" section and Table 4). Therefore, this review may not be so much different from the previous ones, but, of importance, currently most investigations have shown that the beta-adrenoceptor polymorphisms accompanying sympathetic nervous activity contribute to the onset and maintenance of hypertension, diabetes and obesity. PMID- 25115693 TI - Cooperative hybridization of gammaPNA miniprobes to a repeating sequence motif and application to telomere analysis. AB - GammaPNA oligomers having one or two repeats of the sequence AATCCC were designed to hybridize to DNA having one or more repeats of the complementary TTAGGG sequence found in the human telomere. UV melting curves and surface plasmon resonance experiments demonstrate high affinity and cooperativity for hybridization of these miniprobes to DNA having multiple complementary repeats. Fluorescence spectroscopy for Cy3-labeled miniprobes demonstrate increases in fluorescence intensity for assembling multiple short probes on a DNA target compared with fewer longer probes. The fluorescent gammaPNA miniprobes were then used to stain telomeres in metaphase chromosomes derived from U2OS cells possessing heterogeneous long telomeres and Jurkat cells harboring homogenous short telomeres. The miniprobes yielded comparable fluorescence intensity to a commercially available PNA 18mer probe in U2OS cells, but significantly brighter fluorescence was observed for telomeres in Jurkat cells. These results suggest that gammaPNA miniprobes can be effective telomere-staining reagents with applications toward analysis of critically short telomeres, which have been implicated in a range of human diseases. PMID- 25115696 TI - Blood Pressure Variability/Dipper/Non-dipper in Hypertension and Diabetes. AB - It has been well recognized that hypertension in diabetes is a potent risk of micro- and macrovascular complications. BP levels are most important component of BP management. Next to BP levels, other component such as BP variability is also important. BP variability consists of several concepts [1]

1) Very Short term BP variability (beat-to-beat)

2) Short term BP variability (over the 24h)

3) Diurnal BP variation in diabetes

4) Long term BP variability (day-by-day)

5) Visit-to-Visit Variability (months ~ years)

Among these, abnormal circadian rhythm of BP belongs to short-term BP variability. There have been a number of papers about BP variability in recent years. In this chapter, the significance of BP variability in patients with diabetes will be reviewed. PMID- 25115697 TI - Role of Renin-Angiotensin-Aldosterone System in Metabolic Syndrome and Obesity related Hypertension. AB - Several recent clinical trials show that blocking agents of the renin-angiotensin aldosterone system (RAAS) reduce cardiovascular events in patients with metabolic syndrome based on insulin resistance and obesity, especially accumulated visceral fat. Our laboratory has focused on the relationship between the vascular RAAS and the action of insulin on the vasculature. We first revealed that the addition of insulin to cultured vascular smooth muscle cells (VSMC) markedly increases angiotensinogen and angiotensin II (Ang II) expression and production. Insulin addition also induces VSMC growth that is inhibited by the blockade of the RAAS by either ACEI or ARB which suggests a role for the RAAS in insulin-mediated growth. Insulin has a quite different effect on cultured vascular endothelial cells (EC) as it reduces angiotensinogen and renin expression. However, insulin added to EC induces a marked activation of ACE and the activated ACE promotes the conversion of Ang I to Ang II and cell growth under conditions of high insulin concentration. Ang II induces the progression of atherosclerosis through the production of oxidative stress that blocks insulin signaling and accelerates atherosclerosis. In this paper, we attempt to clarify the relationship between insulin resistance, the RAAS, and oxidative stress in vascular tissues to mimic in vivo conditions found in patients with metabolic syndrome and obesity-related hypertension as previously I reviewed in "Current Hypertension Reviews" in 2010 [1]. In addition, I update the relationships between vascular RAAS and insulin resistance for the last 4 years. JSH-2014 [2] states that the target goals of blood pressure (BP) for diabetes patients is lower than 130/80 mmHg, whereas updated JNC 8 [3] and ESH-ESC 2013 [4] recommends the target BP was changed to <140/90 mmHg for hypertensive patients with diabetes. Patients with diabetes and hypertension have reduced mortality as well as improved cardiovascular and cerebrovascular outcomes with treatment to a goal SBP <150 mm Hg, but no randomized controlled trials support a goal <140/90 mm Hg. Despite this, the panel opted for a conservative recommendation in patients with diabetes and hypertension, opting for a goal level of <140/90 mm Hg in adult patients with diabetes and hypertension rather than the evidence based goal of <150/90 mm Hg [3, 5]. JSH-2014 recommends that the first choice of antihypertensive medication should be RAAS blockers such as ACE inhibitor or ARB. For the last several years, several large cohort clinical studies using ACEI and ARB have shown more favorable effects, but aldosterone receptor inhibitor (mineral corticoid receptor inhibitors; MR inhibitors) and Renin Inhibitors have been withdrawn. Some studies showed the strong support to use these medications for diabetic patients. This review will discuss the relationships between vascular RAAS and insulin resistance in patients with hypertension and diabetes as previously reviewed with new updated findings for the last 4 years, and clinical implications based on updated JNC-8, ESH-ESC2013 and JSH-2014. PMID- 25115694 TI - Stomach cancer mortality among workers exposed to asbestos: a meta-analysis. AB - BACKGROUND: The relationship between asbestos and stomach cancer is not well understood because of small number of cases. This study aimed to determine the incidence and mortality of stomach cancer among workers exposed to asbestos based on a systematic review and meta-analysis approach. METHODS: Relevant English electronic databases were systematically searched for published studies characterizing the risk of developing stomach cancer as a result of asbestos exposure. Standardized mortality rate (SMR) for stomach cancer with its 95% confidence interval (CI) was pooled using a fixed-/random-effect model in STATA. RESULTS: A total of 32 independent studies were included for the analysis. The overall SMR for stomach cancer was 1.19 (95% CI 1.06-1.34), with a moderate degree of heterogeneity across the studies (I(2) = 37.6%, P = 0.011). Being male, exposure to crocidolite, miners, studies conducted in Europe and Oceania, and long study follow-up (>= 25 years) all contribute to significantly higher SMR. Significant publication bias was observed. CONCLUSION: Elevated risk of stomach cancer mortality was evidenced among workers exposed to crocidolite, especially male miners. PMID- 25115692 TI - Recent progress in gastric arrhythmia: pathophysiology, clinical significance and future horizons. AB - Gastric arrhythmia continues to be of uncertain diagnostic and therapeutic significance. However, recent progress has been substantial, with technical advances, theoretical insights and experimental discoveries offering new translational opportunities. The discoveries that interstitial cells of Cajal (ICC) generate slow waves and that ICC defects are associated with dysmotility have reinvigorated gastric arrhythmia research. Increasing evidence now suggests that ICC depletion and damage, network disruption and channelopathies may lead to aberrant slow wave initiation and conduction. Histological and high-resolution (HR) electrical mapping studies have now redefined the human 'gastric conduction system', providing an improved baseline for arrhythmia research. The application of HR mapping to arrhythmia has also generated important new insights into the spatiotemporal dynamics of arrhythmia onset and maintenance, resulting in the emergence of new provisional classification schemes. Meanwhile, the strong associations between gastric functional disorders and electrogastrography (EGG) abnormalities (e.g. in gastroparesis, unexplained nausea and vomiting and functional dyspepsia) continue to motivate deeper inquiries into the nature and causes of gastrointestinal arrhythmias. In future, technical progress in EGG methods, new HR mapping devices and software, wireless slow wave acquisition systems and improved gastric pacing devices may achieve validated applications in clinical practice. Neurohormonal factors in arrhythmogenesis also continue to be elucidated and a deepening understanding of these mechanisms may open opportunities for drug design for treating arrhythmias. However, for all translational goals, it remains to be seen whether arrhythmia can be corrected in a way that meaningfully improves organ function and symptoms in patients. PMID- 25115698 TI - Role of the sympathetic nervous activity in hypertension-update in 2014. AB - Many reviews focused on the role of sympathetic nervous activity in hypertension have been published. Recently a new treatment, radiofrequency renal denervation for the treatment of resistant hypertension has been developed and examined in several clinical trials such as the Symplicity HTN and EnligHTN studies. In the Symplicity HTN-1 study the efficacy for lowering blood pressure remained satisfactory at 3 years follow up and many ancillary ameliorative effects have been reported including cardiovascular, psychosocial, and metabolic effects. The purpose of this review is to provide the current findings on the relationships between sympathetic nerve activity and hypertension, especially focus on the importance of renal sympathetic nervous activity for the onset and development of hypertension. In addition, the methods to assess sympathetic nervous activity are reviewed.

The renal denervastion was developed for the treatment resistant hypertensive patients, and excessive confidence of the efficacy and safety existed by the end of 2013, although several issues on the efficacy and safety were reported in 2014. Furthermore, long-term efficacy and impact on renal function have been unclear. Those issues have to be clear for clinical usage. This review will also address the recent data from the renal denervation. PMID- 25115699 TI - An efficient CeO2 /CoSe2 Nanobelt composite for electrochemical water oxidation. AB - CeO2 /CoSe2 nanobelt composite for electrochemical water oxidation: A new CeO2 /CoSe2 nanobelt composite is developed as a highly effective water oxidation electrocatalyst by growing CeO2 nanoparticle CoSe2 nanobelts in situ via a simple polyol reduction route. The constructed hybrid catalyst shows extremely high oxgen evolution reaction (OER) activity, even beyond the state-of-the-art RuO2 catalyst in alkaline media. PMID- 25115700 TI - Endoperoxide polyketides from a Chinese Plakortis simplex: further evidence of the impact of stereochemistry on antimalarial activity of simple 1,2-dioxanes. AB - Chemical investigation of the organic extract obtained from the sponge Plakortis simplex collected in the South China Sea afforded five new polyketide endoperoxides (2 and 4-7), along with two known analogues (1 and 3). The stereostructures of these metabolites have been deduced on the basis of spectroscopic analysis and chemical conversion. The isolated endoperoxide derivatives have been tested for their in vitro antimalarial activity against Plasmodium falciparum strains, showing IC50 values in the low micromolar range. The structure-activity relationships were analyzed by means of a detailed computational investigation and rationalized in the light of the mechanism of action proposed for this class of simple antimalarials. The relative orientation of the atoms involved in the putative radical generation and transfer reaction was demonstrated to have a great impact on the antimalarial activity. The resulting 3D pharmacophoric model can be a useful guide to design simple and effective antimalarial lead compounds belonging to the class of 1,2-dioxanes. PMID- 25115701 TI - A designed conformational shift to control protein binding specificity. AB - In a conformational selection scenario, manipulating the populations of binding competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within the core of ubiquitin, remote from the binding interface, change the binding specificity by shifting the conformational equilibrium of the ground-state ensemble between open and closed substates that have a similar population in the wild-type protein. Binding affinities determined by NMR titration experiments agree with the predictions, thereby showing that, indeed, a shift in the conformational equilibrium enables us to alter ubiquitin's binding specificity and hence its function. Thus, we present a novel route towards designing specific binding by a conformational shift through exploiting the fact that conformational selection depends on the concentration of binding competent substates. PMID- 25115703 TI - The adhesive potential of dentin bonding systems assessed using cuspal deflection measurements and cervical microleakage scores. AB - OBJECTIVES: To assess the cuspal deflection and cervical microleakage of standardized mesio-occluso-distal (MOD) cavities restored with a dimethacrylate resin-based-composite (RBC) placed with one 3-step, one 2-step and three 1-step bonding systems and compared with the unbound condition. METHODS: Forty-eight sound maxillary premolar teeth with standardized MOD cavities were randomly allocated to six groups. Restoration was performed in eight oblique increments using a quartz-tungsten-halogen (QTH) light curing unit (LCU) with the bonding condition as the dependent variable. Buccal and palatal cuspal deflections were recorded post-irradiation using a twin channel deflection measuring gauge at 0, 30, 60 and 180s. Following restoration, the teeth were thermocycled, immersed in a 0.2% basic fuchsin dye for 24h, sectioned and examined for cervical microleakage assessment. RESULTS: The mean total cuspal deflection measurements with the one 3-step, one 2-step and three 1-step bonding systems were 11.26 (2.56), 10.95 (2.16), 10.03 (2.05) (Futurabond((r)) DC SingleDose), 6.37 (1.37) (AdperTM PromptTM L-PopTM), 8.98 (1.34) MUm (All-Bond SE((r))), respectively when compared with the unbound condition (6.46 (1.88) MUm) The one-way ANOVA of the total cuspal deflection measurements identified statistical differences (p<0.001) between groups. Cervical microleakage scores significantly increased (p<0.001) for the negative control (unbound condition) when compared with teeth restored with a bonding system although differences between the bonding systems were evident (p<0.001). SIGNIFICANCE: The cuspal deflection and cervical microleakage protocol reported offers an opportunity to test the bonding technologies available to practitioners for RBCs. Poorly performing adhesives can be identified which indicated the technique may be useful as a screening tool for assessing existing and new bonding technologies which offers the potential to limit complications routinely encountered with Class II RBC restorations. PMID- 25115702 TI - Structure of a stapled peptide antagonist bound to nutlin-resistant Mdm2. AB - As key negative regulator of the p53 tumour suppressor, Mdm2 is an attractive therapeutic target. Small molecules such as Nutlin have been developed to antagonise Mdm2, resulting in p53-dependent death of tumour cells. We have recently described a mutation in Mdm2 (M62A), which precludes binding of Nutlin, but not p53. This Nutlin-resistant variant is not, however, refractory to binding and inhibition by stapled peptide antagonists targeting the same region of Mdm2. A detailed understanding of how stapled peptides are recalcitrant to Mdm2 mutations conferring Nutlin-resistance will aid in the further development of potent Mdm2 antagonists. Here, we report the 2.00 A crystal structure of a stapled peptide antagonist bound to Nutlin resistant Mdm2. The stapled peptide relies on an extended network of interactions along the hydrophobic binding cleft of Mdm2 for high affinity binding. Additionally, as seen in other stapled peptide structures, the hydrocarbon staple itself contributes to binding through favourable interactions with Mdm2. The structure highlights the intrinsic plasticity present in both Mdm2 and the hydrocarbon staple moiety, and can be used to guide future iterations of both small molecules and stapled peptides for improved antagonists of Mdm2. PMID- 25115704 TI - Effect of different surface treatments on the hydrothermal degradation of a 3Y TZP ceramic for dental implants. AB - OBJECTIVES: Implant surface modifications are intended to enhance bone integration. The objective of this study was to assess the effect of different surface treatments on the resistance to hydrothermal degradation, hardness and elastic modulus of a 3Y-TZP ceramic used for dental implants. METHODS: Samples grouped according to their surface morphologies (AS, as-sintered; C, coated; P, dry-polished; R, roughened; PA, polished and annealed; RA, roughened and annealed) were subjected to accelerated hydrothermal degradation (LTD) by exposure to water steam (134 degrees C, 2bars) for 100h. The t-m phase transformation was quantified by grazing incidence X-ray diffraction (GIXDR) and by combined focused ion beam and scanning electron microscopy (FIB-SEM). Elastic modulus and hardness before- and after prolonged aging (100h) were assessed by nanoindentation. RESULTS: AS and C specimens presented a better resistance to hydrothermal degradation than P and R samples. After prolonged aging, the depth of the monoclinic transformed layer ranged from 11MUm to 14MUm. Hydrothermal degradation led to a significant decrease of elastic modulus and hardness. SIGNIFICANCE: Surface treatments affected the resistance to hydrothermal degradation of the 3Y-TZP ceramic. Dry mechanical surface modifications should be avoided since a high t-m transformation rate associated to the initial monoclinic content was observed. Annealing was useful to reverse the initial t-m transformation, but did not improve the resistance to hydrothermal degradation. PMID- 25115707 TI - Editorial Comment from Dr Li to Is the presence of varicocele associated with static and dynamic components of benign prostatic hyperplasia/lower urinary tract symptoms in elderly men? PMID- 25115706 TI - Figmop: a profile HMM to identify genes and bypass troublesome gene models in draft genomes. AB - MOTIVATION: Gene models from draft genome assemblies of metazoan species are often incorrect, missing exons or entire genes, particularly for large gene families. Consequently, labour-intensive manual curation is often necessary. We present Figmop (Finding Genes using Motif Patterns) to help with the manual curation of gene families in draft genome assemblies. The program uses a pattern of short sequence motifs to identify putative genes directly from the genome sequence. Using a large gene family as a test case, Figmop was found to be more sensitive and specific than a BLAST-based approach. The visualization used allows the validation of potential genes to be carried out quickly and easily, saving hours if not days from an analysis. AVAILABILITY AND IMPLEMENTATION: Source code of Figmop is freely available for download at https://github.com/dave-the scientist, implemented in C and Python and is supported on Linux, Unix and MacOSX. CONTACT: curran.dave.m@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 25115705 TI - Modeling dynamic functional relationship networks and application to ex vivo human erythroid differentiation. AB - MOTIVATION: Functional relationship networks, which summarize the probability of co-functionality between any two genes in the genome, could complement the reductionist focus of modern biology for understanding diverse biological processes in an organism. One major limitation of the current networks is that they are static, while one might expect functional relationships to consistently reprogram during the differentiation of a cell lineage. To address this potential limitation, we developed a novel algorithm that leverages both differentiation stage-specific expression data and large-scale heterogeneous functional genomic data to model such dynamic changes. We then applied this algorithm to the time course RNA-Seq data we collected for ex vivo human erythroid cell differentiation. RESULTS: Through computational cross-validation and literature validation, we show that the resulting networks correctly predict the (de) activated functional connections between genes during erythropoiesis. We identified known critical genes, such as HBD and GATA1, and functional connections during erythropoiesis using these dynamic networks, while the traditional static network was not able to provide such information. Furthermore, by comparing the static and the dynamic networks, we identified novel genes (such as OSBP2 and PDZK1IP1) that are potential drivers of erythroid cell differentiation. This novel method of modeling dynamic networks is applicable to other differentiation processes where time-course genome-scale expression data are available, and should assist in generating greater understanding of the functional dynamics at play across the genome during development. AVAILABILITY AND IMPLEMENTATION: The network described in this article is available at http://guanlab.ccmb.med.umich.edu/stageSpecificNetwork. PMID- 25115708 TI - The regulation of Sox2 and Sox9 stimulated by ATP in spinal cord astrocytes. AB - After spinal cord injury (SCI), the level of adenosine triphosphate (ATP) and extracellular matrix (ECM) is increased. Formation of the glial scar is a complex process that is primarily attributed to astrocytic proliferation, and the fibrotic scar results from ECM deposition. In our previous researches, ATP and fibronectin was able to separately stimulate the proliferation of astrocytes. Moreover, fibronectin increases the expression of P2Y1 receptor and offers more binding sites for ATP, which aggravates the proliferation. Meanwhile, ATP was also able to stimulate the release of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha), but fibronectin does not. Recently, it has been reported that over-expressing P2Y1 receptor could promote the level of Sox9. However, the regulation of Sox genes by ATP is still little known in spinal cord astrocytes. In the present study, we discovered that ATP was able to increase the expression of Sox2 and Sox9; fibronectin did not have this direct function. Sox9 was only involved in the proliferation increased by ATP, and Sox2 influenced the release of IL-6 stimulated by ATP. Understanding the critical role of Sox2 and Sox9 mediated by ATP may provide a potential target for therapeutic intervention in spinal cord injury. PMID- 25115709 TI - Similarly up-regulated microRNA-106a in matched formalin-fixed paraffin-embedded and fresh frozen samples and the dynamic changes during gastric carcinogenesis and development. AB - Evidence increasingly suggests that miR-106a is always elevated in gastric cancer; however, little is known about the expression trend and clinical significance in the whole process of gastric carcinogenesis and development. To investigate the dynamic changes of miR-106a in each stage during gastric carcinogenesis, we used formalin-fixed, paraffin-embedded (FFPE) tissues which had been reported to have valuable information for miRNA research in our previous studies. Here, we compared the expression of miR-106a in FFPE and fresh frozen tissues using real-time polymerase chain reaction. On the basis of the high correlation of miR-106a quantitative data from the two resources, FFPE samples were subsequently performed to elucidate the location and expression of miR-106a using in situ hybridization in sequential tissues, including normal gastric mucosa, chronic atrophic gastritis combined with various degrees of dysplasia, early and advanced gastric cancer. Finally, we found that miR-106a was similarly up-regulated in gastric cancer regardless of sample types although fragmentation existed inevitably in FFPE tissues. Notably, the frequency and extent of miR-106a expression gradually increased during the transition from atypical hyperplasia to advanced carcinoma and had already had positive signals in early precancerous lesions but negative signals in normal gastric mucosal epithelial cells. Our research, according to these results, indicated that FFPE samples can serve as an important research tool for miRNA field, and the early changes of miR-106a detected in such samples may have clinical application as a potential biomarker for the discovery and diagnosis of gastric cancer. PMID- 25115710 TI - Hourly differences in air pollution and risk of respiratory disease in the elderly: a time-stratified case-crossover study. AB - BACKGROUND: Epidemiological studies have shown adverse effects of short-term exposure to air pollution on respiratory disease outcomes; however, few studies examined this association on an hourly time scale. We evaluated the associations between hourly changes in air pollution and the risk of respiratory disease in the elderly, using the time of the emergency call as the disease onset for each case. METHODS: We used a time-stratified case-crossover design. Study participants were 6,925 residents of the city of Okayama, Japan, aged 65 or above who were taken to hospital emergency rooms between January 2006 and December 2010 for onset of respiratory disease. We calculated city-representative hourly average concentrations of air pollutants from several monitoring stations. By using conditional logistic regression models, we estimated odds ratios per interquartile-range increase in each pollutant by exposure period prior to emergency call, adjusting for hourly ambient temperature, hourly relative humidity, and weekly numbers of reported influenza cases aged >=60. RESULTS: Suspended particulate matter (SPM) exposure 24 to <72 hours prior to the onset and ozone exposure 48 to <96 hours prior to the onset were associated with the increased risk of respiratory disease. For example, following one interquartile range increase, odds ratios were 1.05 (95% confidence interval: 1.01, 1.09) for SPM exposure 24 to <48 hours prior to the onset and 1.13 (95% confidence interval: 1.04, 1.23) for ozone exposure 72 to <96 hours prior to the onset. Sulfur dioxide (SO2) exposure 0 to <24 hours prior to onset was associated with the increased risk of pneumonia and influenza: odds ratio was 1.07 per one interquartile-range increase (95% confidence interval: 1.00, 1.14). Elevated risk for pneumonia and influenza of SO2 was observed at shorter lags (i.e., 8-18 hours) than the elevated risks for respiratory disease of SPM or ozone. Overall, the effect estimates for chronic obstructive pulmonary disease and allied conditions were equivocal. CONCLUSIONS: This study provides further evidence that hourly changes in air pollution exposure increase the risks of respiratory disease, and that SO2 may be related with more immediate onset of the disease than other pollutants. PMID- 25115712 TI - [Anticipated efficacy of HPV vaccination in prophylaxis against nongenital cancers]. AB - BACKGROUND: There is a considerable number of studies on the efficacy HPV (human papillomavirus) vaccination against different cancers but relevant information is scattered in diverse journals. This paper is a review summarizing current knowledge of the potential of HPV vaccination against all HPV related cancers. AIM: HPV infection is probably the most frequent sexually transmitted disease. At least 13 HPV genotypes are classified as carcinogenic or probably carcinogenic in respect to cervical cancer. Almost 100% of cervical cancers are linked to HPV infection. HPV 16 and HPV 18 are the most frequently involved genotypes and account together for approximately 70% of cervical cancer in the world. Persistent high risk HPV infection is responsible for a significant proportion of vulvar, vaginal, anal and penile carcinomas. The virus has also been implicated in oncogenesis of head and neck cancers, including oropharyngeal cancers. HPV infection can play an important role in cancerogenesis of lung, esophagus, breast, and colon and rectum. On the contrary, published results indicate that HPV infection is not associated with prostate oncogenesis. Strong predominance of HPV 16 has been reported for all HPV associated cancer sites. Generally, it is estimated that approximately 5.2% of all cancers are associated with oncogenic HPV infection. Currently, there are two vaccines on the market; quadrivalent Silgard(r) (Gardasil(r)) and bivalent CervarixTM. Large trials for both vaccines have shown efficacy against HPV related infection and disease. Efficacy has been very high in HPV naive subjects to vaccine related types. While HPV vaccination is currently approved for the prevention of cervical cancer, it also has the potential in the prevention of all HPV associated malignancies. The Czech republic belongs to countries that cover HPV vaccination of girls at the age of 13- 14 years by general health insurance. Overall impact of this vaccination remains to be evaluated. The new issues of the role of HPV in oncogenesis, as well as the potential effect of HPV vaccination against HPV related nongenital cancers are discussed. CONCLUSION: Approximately 5.2% of all human cancers are associated with oncogenic human papillomavirus infection. HPV vaccination against the most risky HPV oncotypes may cause a significant reduction of these cancers mainly in the HPV naive population. PMID- 25115713 TI - [Brazilian story of the R337H p53 mutation]. AB - The p53 tumor suppressor is an evergreen of molecular oncology. Since its discovery in 1979, it has been subjected to intensive investigation. The p53 protein is composed of "only" 393 amino acid residues, and function of almost each of them has been addressed in detail. Somatic mutations are extremely frequent, they can be found almost in each of the p53 codons and in all types of tumors. Inherited p53 mutations are rare but very penetrant, and they are typically associated with development of a broad spectrum of tumors. However, in 2001, the p53 research provided an unexpected discovery: the R337H allele was found in southern Brazil. This allele was atypically associated with only one type of tumor - childhood adrenocortical carcinoma and it exhibited low penetrance. Therefore, new data on functioning and impact of the R337H mutation were highly desired. The results obtained during a few following years helped to elucidate not only this specific p53 variant but also provided insight into general principles of mutant p53 variants function. It also turned out that all R337H alleles that are very frequent in southern Brazil originate from one common ancestor. PMID- 25115711 TI - Mobile elements and chromosomal changes associated with MLS resistance phenotypes of invasive pneumococci recovered in the United States. AB - Pneumococcal macrolide resistance is usually expressed as one of two phenotypes: the M phenotype conferred by the mef gene or the MLSB phenotype caused by modification of ribosomal targets, most commonly mediated by an erm methylase. Target-site modification leading to antibiotic resistance can also occur due to sequence mutations within the 23S rRNA or the L4 and L22 riboproteins. We screened 4,535 invasive isolates resistant to erythromycin and 18 invasive isolates nonsusceptible to quinupristin-dalfopristin (Q-D) to deduce the potential mechanisms involved. Of 4,535 erythromycin-resistant isolates, 66.2% were polymerase chain reaction (PCR)-positive for mef alone, 17.8% for ermB alone, and 15.1% for both mef and ermB. Thirty-seven isolates (0.9%) were PCR negative for both determinants. Of these, 3 were positive for ermA (subclass ermTR) and 25 had chromosomal mutations. No chromosomal mutations (in 23S rRNA, rplD, or rplV) nor any of the macrolides/lincosamides/streptogramin (MLS) resistance genes screened for (ermT, ermA, cfr, lsaC, and vgaA) were found in the remaining nine isolates. Of 18 Q-D nonsusceptible isolates, 14 had chromosomal mutations and one carried both mef and ermB; no chromosomal mutations or other resistance genes were found in 3 isolates. Overall, we found 28 mutations, 13 of which have not been previously described in Streptococcus pneumoniae. The role of these mutations remains to be confirmed by transformation assays. PMID- 25115714 TI - [The cost study of first- line treatment of metastatic colorectal carcinoma with bevacizumab- containing regimen in the Czech Republic]. AB - BACKGROUND: Bevacizumab, a humanized monoclonal IgG antibody against the vascular endothelial growth factor (VEGF), is reimbursed in combination with chemotherapy for the first and subsequent line treatment of patients with metastatic colorectal cancer (mCRC) in the Czech Republic. However, its high cost is a potentially limiting factor. We assessed the cost of bevacizumab in the treatment of mCRC in a comprehensive cancer center. PATIENTS AND METHODS: A total of 218 patients were included in our analysis. Cost data (examination, medication, hospitalization) were collected since the initiation of bevacizumab treatment to any tumor response (RECIST criteria: complete response - CR, partial response - PR, stable disease - SD, progressive disease - PD) and/ or to death. Minimal followup for all patients was 28 months. Costs were valued in Czech crowns (CZK) and converted to EUR (1? = 25.14 CZK). RESULTS: PD was recorded in 194 patients (89% of patients). The mean cost of treatment to PD (median TTP 9.1 months) was 1,002,076.30 CZK (39,859.84 EUR). The majority of costs to PD was made by medication - 917,048.60 CZK (36,477.67 EUR) per patient. The mean cost to response PR, CR or SD was 1,105,823.10 CZK (43,986.60 EUR) after median 9.8 months of treatment (recorded for 21 patients), medication formed 1,023,827.70 CZK (40,725.05 EUR). During the study, 170 patients (78%) died. The mean of the total costs since initiation of treatment to death (median OS 18.8 months) was 1,338,874.20 CZK (53,256.70 EUR) - out of that, medication was 1,184,251.10 CZK (47,106.25 EUR) per patient. CONCLUSION: Targeted bio-logical therapy is the largest part of the costs of mCRC therapy. Cost of bevacizumab made up to 69% of costs to PD - 687,608.20 CZK ( 27,351.20 EUR ) per patient. The majority of the total cost was formed by targeted drug therapy (bevacizumab in 1st line therapy, cetuximab and panitumumab in 2nd and 3rd line therapy); 58% of total costs since initiation of treatment to death - 778,233.80 CZK (30,956 EUR) per patient. PMID- 25115715 TI - [Screening of malnutrition risk versus indicators of nutritional status and systemic inflammatory response in newly diagnosed lung cancer patients]. AB - BACKGROUND: Most lung cancers are already advanced at the time of dia-gnosis. In these patients, a frequent symptom is protein energy malnutrition, often diagnosed prior to oncological treatment. Malnutrition results in poor tolerance of treatment and increased morbidity and mortality. METHODS: Nutritional Risk Screening (NRS) 2002 adapted for oncological patients was used to assess the risk of undernutrition in a group of 188 lung cancer patients. The risk was evaluated on a 6- point scale according to common signs of nutritional status and tumor and its treatment risk factors. A score of 3 and more (called "nutritional risk") means a significant risk of malnutrition. Furthermore, pretreatment nutritional characteristics were evaluated in patients (including the value of BMI) and laboratory values indicating malnutrition/ acute phase response (albumin/ C reactive protein - CRP). RESULTS: Acceptable NRS score was found in 50.6%, while in 45.3% was suggested into risk of malnutrition ("nutritional risk"). Only 6.6% of our patients had a BMI less than 20 kg/ m2. Significant differences in albumin and CRP values in various categories of NRS were confirmed. CONCLUSION: Initial signs of cancer malnutrition may be overlooked in patients who fall within or above the range of BMI for adequate weight, although these patients may be at significant risk of malnutrition. The indicators of nutritional status and systemic inflammatory responses were significantly associated with resulting values NRS score. PMID- 25115716 TI - [Relation between carbonic anhydrase IX serum level, hypoxia and radiation resistance of head and neck cancers]. AB - BACKGROUND: Hypoxia of locally advanced head and neck cancers is one of the main causes of their radiation resistance that presents clinically as a persistence of residual tumor disease after radiation therapy. Therefore, detection of tumor hypoxia could be an important predictor of treatment efficacy. Carbonic anhydrase IX (CA IX) is a protein, coded by a homonymous gene, the expression of which increases in tumor tissues at hypoxic conditions. Hence, CA IX represents an endogenic marker of tumor hypoxia, identifiable in tumor tissues, and its soluble extracellular domain can also be detected in body fluids of the patient. The primary endpoint of this study was to explore whether a correlation exists between CA IX serum level and the residual tumor disease after therapy. The secondary endpoint was to find out how the serum concentration of CA IX changes during the course of fractionated radiation therapy. MATERIALS AND METHODS: The presented prospective monocentric clinical study evaluated a population of 30 patients with locally advanced squamous cell head and neck cancers, treated by radiation therapy or concurrent chemo radiation therapy with a curative intent. The serum concentration of the soluble form of CA IX was examined from a venous blood sample, using sandwich enzyme linked immunosorbent assay (ELISA). The blood samples were obtained before the treatment initiation, in the middle of radiation therapy, at the time of finishing radiation therapy and six weeks after the treatment completion. RESULTS: We found a substantial variability in the CA IX levels measured in the examined population, ranging 0- 1,696 pg/ ml. We found no significant changes in the mean value of CA IX concentration during the course of radiation therapy and after the treatment completion. In 11 patients (36.7%), the treatment resulted in complete remission of the disease. In these patients, lower average pretreatment levels of CA IX were noted when compared to patients with persistence of residual tumor disease (37.57 vs 77.47; p = 0.154). CONCLUSION: The results indicate that serum level of CA IX in patients with locally advanced head and neck cancers does not change significantly during the course of fractionated radiation therapy. The relation between CA IX serum level and residual tumor disease after radiation therapy requires verification on a larger population of patients. PMID- 25115717 TI - Impact of anakinra treatment on cytokine and lymphocytes/ monocytes profile of an Erdheim-Chester patient. AB - BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans cells histiocytosis associated with intense immune activation. In our clinical center, an ECD patient was treated with anakinra, IL1RA (interleukin1 receptor antagonist), resulting in clinical improvement and major decrease of pathological fatigue. The aim of the study was to evaluate changes in cytokine profile and shift of immune cells estimated by flow cytometric analysis of ECD patient before, during initial stages of anakinra treatment as well as after treatment ceased in comparison to healthy donors. METHODS: Singleplex reactions of 19 individual cytokines from serum of ECD patient were measured by FACS array. Flow cytometric analyses were performed on peripheral blood cells. RESULTS: The most striking result is substantial decrease of IL6 immediately after anakinra treatment started suggesting a major role of IL1 pathway in ECD pathophysiology. As for flow cytometric analysis, increased number of CD16+ monocytes before treatment is a new finding. CONCLUSION: Our results suggest that IL6 may be a marker of early treatment response of ECD patients treated with anakinra. PMID- 25115718 TI - Positron emission tomography combined with computed tomography for diagnosis of synchronous tumors. AB - BACKGROUND: The hybrid method 18F-FDG PET/ CT has been proven as a method of choice in oncology for diagnostics, staging, restaging of the tumor and evaluation of the therapeutic effect. The aim of the study was to determine the value of 18F-FDG PET/ CT for detection of synchronous tumors and consequently the influence on the patients management. MATERIAL AND METHODS: The examinations were performed on Discovery, GE Healthcare PET/ CT using standard protocol. Among the patients, examined by 18F FDG PET/ CT for one year (n = 1 408), unsuspected synchronous tumors were detected in 11 cases (0.8%). RESULTS: Five pulmonary carcinomas, four head and neck squamous cell carcinomas (HNSCC), one ovarian carcinoma and one tumor of the sigma were detected as second malignancies. The histology verification was done in five cases (all HNSCC and one sigma carcinoma). In one patient with ovarian carcinoma, histology was obtained after surgery. In the rest of patients, no verification was undertaken because of the patients refusal and the advanced stage of the diseases, demanding systemic chemotherapy. Four patients (three with HNSCC and one with ovarian secondary malignancy) had favorable outcome during the nine month follow up. CONCLUSION: The hybrid method PET/ CT, combining the metabolic and morphologic findings, can help detection of synchronous malignancies in a small percentage of cases, but with a positive influence on management of considerable part of such patients. PMID- 25115719 TI - [Paraneoplastic vasculitis in a patient with cervical cancer]. AB - BACKGROUND: Paraneoplastic syndromes precede the dia-gnosis of malignancy. Early detection of paraneoplastic syndrome may lead to detection of malignancy in its early and potentially curable stage. Differential diagnostic process of rare paraneoplastic vasculitis requires multidisciplinary cooperation between rheumatologists, radiologists and oncologists. CASE: 41 year old female patient with cervical cancer in stage IVB (paraaortic lymphadenopathy) and clinical symptoms of acute vasculitis was admitted to our ward for oncological treatment. Chemoradiotheraphy was initiated concurrently with corticotherapy. During the treatment we observed alleviation of vasculitis related symptoms. Ongoing followup, however, brought no further improvement in vasculitis related symptoms. This lead us to suspicion of recurrence, confirmed on CT scan. Palliative chemotherapy was without any effect and due to worsening performance status was terminated. CONCLUSION: The activity of vasculitis was closely associated with the activity of primary malignant disease. Early recognition of paraneoplastic syndrome may contribute not only to dia-gnosis of malignancy, but is helpful during followup of these patients. PMID- 25115720 TI - [Acupuncture in the treatment of symptoms of oncological diseases in the Western world]. AB - Acupuncture is one of the methods of traditional Chinese Medicine (TCM). In Asia, methods of TCM are quite often used in oncological patients in combination with classical medicine. In Europe and North America, the position of the TCM is not so clear. In the last few years, some studies were done which were supposed to verify scientifically the effectiveness of acupuncture in the treatment of some symptoms in oncological patients and adverse effects of oncological treatment. Results of these studies indicate that acupuncture is effective in the treatment of pain, nausea, vomiting and xerostomia. The International Society of Integrative Oncology formulated some recommendations for using methods of TCM in oncological patients. In this field, there is still a lot of possibilities for further studies which could help acupuncture to become an important therapeutic method even in our region. PMID- 25115721 TI - Dendritic cell vaccines against non-small cell lung cancer - an emerging therapeutic alternative. AB - Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic cell-based vaccines on cancer patients. Herewith, we describe the clinical trials of nonsmall cell lung cancer (NSCLC) published in the literature. Although the number of clinical trials and NSCLC patients enrolled in these studies is small, it is possible to conclude that the administration of dendritic cells (DCs) by any route is safe and that a clinical benefit after their administration can be observed. These initial results encourage continued investigation in clinical trials into the benefit of DCs along with different strategies to enhance their immune response in this deadly disease. PMID- 25115725 TI - The use of the cluster randomized crossover design in clinical trials: protocol for a systematic review. AB - BACKGROUND: The cluster randomized crossover (CRXO) design is gaining popularity in trial settings where individual randomization or parallel group cluster randomization is not feasible or practical. In a CRXO trial, not only are clusters of individuals rather than individuals themselves randomized to trial arms, but also each cluster participates in each arm of the trial at least once in separate periods of time.We will review publications of clinical trials undertaken in humans that have used the CRXO design. The aim of this systematic review is to summarize, as reported: the motivations for using the CRXO design, the values of the CRXO design parameters, the justification and methodology for the sample size calculations and analyses, and the quality of reporting the CRXO design aspects. METHODS/DESIGN: We will identify reports of CRXO trials by systematically searching MEDLINE, PubMed, Cochrane Methodology Register, EMBASE, and CINAHL Plus. In addition, we will search for methodological articles that describe the CRXO design and conduct citation searches to identify any further CRXO trials. The references of all eligible trials will also be searched. We will screen the identified abstracts, and retrieve and assess for inclusion the full text for any potentially relevant articles. Data will be extracted from the full text independently by two reviewers. Descriptive summary statistics will be presented for the extracted data. DISCUSSION: This systematic review will inform both researchers addressing CRXO methodology and trialists considering implementing the design. The results will allow focused methodological research of the CRXO design, provide practical examples for researchers of how CRXO trials have been conducted, including any shortcomings, and highlight areas where reporting and conduct may be improved. PMID- 25115726 TI - A new microscopic insight into membrane penetration and reorganization by PETIM dendrimers. AB - Dendrimers are highly branched polymeric nanoparticles whose structure and topology, largely, have determined their efficacy in a wide range of studies performed so far. An area of immense interest is their potential as drug and gene delivery vectors. Realizing this potential, depending on the nature of cell surface-dendrimer interactions, here we report controlled model membrane penetration and reorganization, using a model supported lipid bilayer and poly(ether imine) (PETIM) dendrimers of two generations. By systematically varying the areal density of the lipid bilayers, we provide a microscopic insight, through a combination of high resolution scattering, atomic force microscopy and atomistic molecular dynamics simulations, into the mechanism of PETIM dendrimer membrane penetration, pore formation and membrane re-organization induced by such interactions. Our work represents the first systematic observation of a regular barrel-like membrane spanning pore formation by dendrimers, tunable through lipid bilayer packing, without membrane disruption. PMID- 25115728 TI - Volatile constituents of Dianthus rupicola Biv. from Sicily: activity against microorganisms affecting cellulosic objects. AB - Dianthus rupicola Biv. (cliffs carnation) is a camephytic, suffruticous, perennial plant growing up to 40 cm high. The plant is widespread in Sicily and neighbouring islands (Egadi, Lampedusa, Lipari) and in some areas of southern Italy. GC and GC-MS analyses of the essential oil distilled from the flowers showed the presence of 66 components. Its composition is characterised by the high content of thymol and carvacrol derivatives. A good antibacterial activity against Bacillus cereus and Bacillussubtilis, both infesting cellulosic historical material, was shown, whereas the antioxidant capacity was determined to be quite poor. PMID- 25115727 TI - Lithium ameliorates lipopolysaccharide-induced microglial activation via inhibition of toll-like receptor 4 expression by activating the PI3K/Akt/FoxO1 pathway. AB - BACKGROUND: Lithium, an effective mood stabilizer for the treatment of bipolar disorders, has been recently suggested to have a role in neuroprotection during neurodegenerative diseases. The pathogenesis of neurological disorders often involves the activation of microglia and associated inflammatory processes. Thus, in this study, we aimed to understand the role of lithium in microglial activation and to elucidate the underlying mechanism(s). METHODS: Primary microglial cells were pretreated with lithium and stimulated with lipopolysaccharide (LPS). The cells were assessed regarding the responses of pro inflammatory cytokines, and the associated signaling pathways were evaluated. RESULTS: Lithium significantly inhibited LPS-induced microglial activation and pro-inflammatory cytokine production. Further analysis showed that lithium could activate PI3K/Akt signaling. Analyses of the associated signaling pathways demonstrated that the lithium pretreatment led to the suppression of LPS-induced toll-like receptor 4 (TLR4) expressions via the PI3K/Akt/FoxO1 pathway. CONCLUSIONS: This study demonstrates that lithium can inhibit LPS-induced TLR4 expression and microglial activation through the PI3K/Akt/FoxO1 signaling pathway. These results suggest that lithium plays an important role in microglial activation and neuroinflammation-related diseases, which may lead to a new therapeutic strategy for the treatment of neuroinflammation-related disorders. PMID- 25115729 TI - Reducing readmissions following paediatric cardiothoracic surgery: a quality improvement initiative. AB - BACKGROUND: We have previously identified risk factors for readmission following congenital heart surgery - Hispanic ethnicity, failure to thrive, and original hospital stay more than 10 days. As part of a quality initiative, changes were made to the discharge process in hopes of reducing the impact. All discharges were carried out with an interpreter, medications were delivered to the hospital before discharge, and phone calls were made to families within 72 hours following discharge. We hypothesised that these changes would decrease readmissions. METHODS: The current cohort of 635 patients underwent surgery in 2012. Demographic, preoperative, operative, and postoperative variables were evaluated. Univariate and multivariate risk factor analyses were performed. Comparisons were made between the initial (2009) and the current (2012) cohorts. RESULTS: There were 86 readmissions of 77 patients during 2012. Multivariate risk factors for readmission were risk adjustment for congenital heart surgery score and initial hospital stay >10 days. In comparing 2009 with 2012, the overall readmission rate was similar (10 versus 12%, p=0.27). Although there were slight decreases in the 2012 readmissions for those patients with Hispanic ethnicity (18 versus 16%, p=0.79), failure to thrive (23 versus 17%, p=0.49), and initial hospital stay >10 days (22 versus 20%, p=0.63), they were not statistically significant. CONCLUSIONS: Potential risk factors for readmission following paediatric cardiothoracic surgery have been identified. Although targeted modifications in discharge processes can be made, they may not reduce readmissions. Efforts should continue to identify modifiable factors that can reduce the negative impact of hospital readmissions. PMID- 25115730 TI - How do recent classifications give a new insight for the management of emphysematous pyelonephritis? PMID- 25115731 TI - Extracellular molecular effectors mediating probiotic attributes. AB - Interest in probiotic bacteria, in the context of health and disease, is increasing and gathering scientific evidence, as is reflected by their growing utilization in food and pharma industry. As a consequence, many research effort over the past few years has been dedicated to discern the molecular mechanisms responsible for their purported attributes. Remarkably, whereas the traditional probiotic concept assumes that bacteria must be alive during their administration to exert health-promoting effects, evidence is being accumulated that supports defined bacterial secreted molecules and/or isolated surface components mediating attributed cross talk dialogue between the host and the probiotic cells. Indeed, administration of the isolated bacterial-derived metabolites or molecules may be sufficient to promote the desired effects and may represent a promising safer alternative in inflammatory disorders. Here, we summarize the current knowledge of molecular effectors of probiotic bacteria that have been involved in mediating their effects. PMID- 25115732 TI - Comparative study of the metal accumulation in Hysterothalycium reliquens (nematode) and Paraphilometroides nemipteri (nematode) as compared with their doubly infected host, Nemipterus peronii (Notched threadfin bream). AB - In February 2013, forty-seven Notched threadfin bream, the Nemipterus peronii, were sampled from the eastern coastal waters of the South China Sea. The concentration of various elements, namely cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), strontium (Sr), manganese (Mn), selenium (Se), Lead (Pb), nickel (Ni), aluminum (Al), arsenic (As), iron (Fe), and Zinc (Zn) were analyzed in the liver, muscle, and kidney organs of the host, as well as in their parasites Hysterothalycium reliquens (nematode) and the Paraphilometroides nemipteri (nematode), using inductively coupled plasma mass spectrometry (ICP MS). The former group of parasites showed highest accumulation capacity for Cr, Cu, Fe, Mn, Se, Ni, and Zn while the latter group had high accumulation potential of As, Hg, Cd, Al, Pb, and Sr. The divergence in heavy-metal accumulation profiles of both nematodes is linked with the specificity of microhabitats, cuticle morphology, and interspecific competition. The outcome of this study indicates that both parasite models can be used for biomonitoring of metal pollution in marine ecosystems. PMID- 25115735 TI - Anode catalysts for direct hydrazine fuel cells: from laboratory test to an electric vehicle. AB - Novel highly active electrocatalysts for hydrazine hydrate fuel cell application were developed, synthesized and integrated into an operation vehicle prototype. The materials show in both rotating disc electrode (RDE) and membrane electrode assembly (MEA) tests the world highest activity with peak current density of 16,000 A g(-1) (RDE) and 450 mW cm(-2) operated in air (MEA). PMID- 25115734 TI - Vasorelaxation induced by methyl cinnamate, the major constituent of the essential oil of Ocimum micranthum, in rat isolated aorta. AB - The aim of the present study was to investigate the vascular effects of the E isomer of methyl cinnamate (E-MC) in rat isolated aortic rings and the putative mechanisms underlying these effects. At 1-3000 MUmol/L, E-MC concentration dependently relaxed endothelium-intact aortic preparations that had been precontracted with phenylephrine (PHE; 1 MUmol/L), with an IC50 value (geometric mean) of 877.6 MUmol/L (95% confidence interval (CI) 784.1-982.2 MUmol/L). These vasorelaxant effects of E-MC remained unchanged after removal of the vascular endothelium (IC50 725.5 MUmol/L; 95% CI 546.4-963.6 MUmol/L) and pretreatment with 100 MUmol/L N(G) -nitro-l-arginine methyl ester (IC50 749.0 MUmol/L; 95% CI 557.8-1005.7 MUmol/L) or 10 MUmol/L 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (IC50 837.2 MUmol/L; 95% CI 511.4-1370.5 MUmol/L). Over the concentration range 1 3000 MUmol/L, E-MC relaxed K(+) -induced contractions in mesenteric artery preparations (IC50 314.5 MUmol/L; 95% CI 141.9-697.0 MUmol/L) with greater potency than in aortic preparations (IC50 1144.7 MUmol/L; 95% CI 823.2-1591.9 MUmol/L). In the presence of a saturating contractile concentration of K(+) (150 mmol/L) in Ca(2+) -containing medium combined with 3 MUmol/L PHE, 1000 MUmol/L E MC only partially reversed the contractile response. In contrast, under similar conditions, E-MC nearly fully relaxed PHE-induced contractions in aortic rings in a Ba(2+) -containing medium. In preparations that were maintained under Ca(2+) free conditions, 600 and 1000 MUmol/L E-MC significantly reduced the contractions induced by exogenous Ca(2+) or Ba(2+) in KCl-precontracted preparations, but not in PHE-precontracted preparations (in the presence of 1 MUmol/L verapamil). In addition, E-MC (1-3000 MUmol/L) concentration-dependently relaxed the contractions induced by 2 mmol/L sodium orthovanadate. Based on these observations, E-MC-induced endothelium-independent vasorelaxant effects appear to be preferentially mediated by inhibition of plasmalemmal Ca(2+) influx through voltage-dependent Ca(2+) channels. However, the involvement of a myogenic mechanism in the effects of E-MC is also possible. PMID- 25115736 TI - Polymer-free patterning of graphene at sub-10-nm scale by low-energy repetitive electron beam. AB - A polymer-free technique for generating nanopatterns on both synthesized and exfoliated graphene sheets is proposed and demonstrated. A low-energy (5-30 keV) scanning electron beam with variable repetition rates is used to etch suspended and unsuspended graphene sheets on designed locations. The patterning mechanisms involve a defect-induced knockout process in the initial etching stage and a heat induced curling process in a later stage. Rough pattern edges appear due to inevitable stochastic knockout of carbon atoms or graphene structure imperfection and can be smoothed by thermal annealing. By using this technique, the minimum feature sizes achieved are about 5 nm for suspended and 7 nm for unsuspended graphene. This study demonstrates a polymer-free direct nanopatterning approach for graphene. PMID- 25115733 TI - The major bioactive components of seaweeds and their mosquitocidal potential. AB - Seaweeds are one of the most widely studied natural resources for their biological activities. Novel seaweed compounds with unique chemical structures have been reported for their pharmacological properties. The urge to search for novel insecticidal compound with a new mode of action for development of botanical insecticides supports the relevant scientific research on discovering the bioactive compounds in seaweeds. The mosquitocidal potential of seaweed extracts and their isolated compounds are documented in this review paper, along with the discussion on bioactivities of the major components of seaweeds such as polysaccharides, phenolics, proteins, terpenes, lipids, and halogenated compounds. The effects of seaweed extracts and compounds toward different life stages of mosquito (egg, larva, pupa, and adult), its growth, development, and reproduction are elaborated. The structure-activity relationships of mosquitocidal compounds are discussed to extrapolate the possible chemical characteristics of seaweed compounds responsible for insecticidal properties. Furthermore, the possible target sites and mode of actions of the mosquitocidal seaweed compounds are included in this paper. The potential synergistic effects between seaweeds and commercial insecticides as well as the toxic effects of seaweed extracts and compounds toward other insects and non-target organisms in the same habitat are also described. On top of that, various factors that influence the mosquitocidal potential of seaweeds, such as abiotic and biotic variables, sample preparation, test procedures, and considerations for a precise experimental design are discussed. The potential of active seaweed extracts and compounds in the development of effective bioinsecticide are also discussed. PMID- 25115737 TI - Clinical outcomes of children and adults with central nervous system primitive neuroectodermal tumor. AB - Central nervous system primitive neuroectodermal tumors (CNS PNETs) predominantly occur in children and rarely in adults. Because of the rarity of this tumor, its outcomes and prognostic variables are not well characterized. The purpose of this study was to evaluate clinical outcomes and prognostic factors for children and adults with CNS PNET. The records of 26 patients (11 children and 15 adults) with CNS PNET from 1991 to 2011 were reviewed retrospectively. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method, and relevant prognostic factors were analyzed. For the cohort, both the 5-year DFS and the OS were 46 %. For pediatric patients, the 5-year DFS was 78 %; for adult patients, it was 22 % (P = 0.004). Five-year OS for the pediatric and adult patients was 67 and 33 %, respectively (P = 0.07). With bivariate analysis including chemotherapy regimen (high dose vs. standard vs. nonstandard) or risk stratification (standard vs. high) and age, the increased risk of disease recurrence in adults persisted. A nonsignificant tendency toward poorer OS in adult patients relative to pediatric patients also persisted. High-dose chemotherapy with stem cell rescue was associated with a statistically significant improvement in OS and a tendency toward improved DFS, although the findings were mitigated when the effect of age was considered. Local recurrence was the primary pattern of treatment failure in both adults and children. Our results suggest that adult patients with CNS PNETs have inferior outcomes relative to the pediatric cohort. Further research is needed to improve outcomes for CNS PNET in populations of all ages. PMID- 25115739 TI - Impact of health-related quality of life and fatigue on survival of recurrent high-grade glioma patients. AB - Quality of life (QoL) impairment and fatigue are frequently experienced during treatment for recurrent high-grade glioma (HGG). Fatigue and QoL impairments can be due to primary neurological dysfunction, cytotoxic treatments, mood disturbances, and supportive medications. We now seek to understand how QoL and fatigue impacts survival in recurrent HGG. Using a prospective observational design, 237 patients with recurrent HGG and KPS >=70 completed a self administered questionnaire that evaluated QoL and fatigue. QoL was assessed with Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Brain (FACT-Br) scales while fatigue was assessed using Functional Assessment of Chronic Illness Therapy (FACIT-F) scale. Cox proportional hazard models were utilized to evaluate the association between QoL and fatigue and survival. Seventy-three (31 %) subjects had recurrent WHO grade III gliomas and 164 (69 %) had recurrent WHO grade IV gliomas. Median follow-up analysis was 27.60 months. In univariate Cox analyses, the FACT-Br specific subscale (HR 0.88; CI 95 %, 0.77-1; p = 0.048) and FACIT-F (HR 0.82; CI 95 %, 0.68-0.99; p = 0.045) were both significant predictors of survival. Fatigue added prognostic information beyond that provided by KPS, age, sex, tumor grade, and number of prior progressions (HR 0.80; CI 95 %, 0.68 0.9; p = 0.031). A greater degree of fatigue was associated with poorer survival in recurrent HGG patients. In multivariable analyses, FACT-G and FACT-Br are not independent predictors of prognosis. Fatigue is a strong independent predictor of survival that provides incremental prognostic value to the traditional markers of prognosis in recurrent HGG. Pharmacological or non-pharmacological strategies to treat fatigue warrant investigation. PMID- 25115738 TI - Therapeutic implications of CD1d expression and tumor-infiltrating macrophages in pediatric medulloblastomas. AB - Immunobiology of medulloblastoma (MB), the most common malignant brain tumor in children, is poorly understood. Although tumor cells in some MBs were recently shown to express CD1d and be susceptible to Valpha24-invariant natural killer T (NKT)-cell cytotoxicity, the clinical relevance of CD1d expression in MB patients remains unknown. We investigated the expression of CD1d in pediatric MBs and correlated with molecular and clinical characteristics. Specifically, we explored if NKT cell therapy can be targeted at a subset of pediatric MBs with poorer prognosis. Particularly, infantile MBs have a worse outcome because radiotherapy is delayed to avoid neurocognitive sequelae. Immunohistochemistry for CD1d was performed on a screening set of 38 primary pediatric MBs. Gene expression of the membrane form of M2 macrophage marker, CD163, was studied in an expanded cohort of 60 tumors. Outcome data was collected prospectively. Thirteen of 38 MBs (34.2 %) expressed CD1d on immunohistochemistry. CD1d was expressed mainly on MB tumor cells, and on some tumor-associated macrophages. Majority (18/22, 82 %) of non sonic-hedgehog/Wingless-activated MBs (group 3 and 4) were CD1d-negative (p = 0.05). A subset of infantile MBs (4/9, 44.4 %) expressed CD1d. Macrophages infiltrating MB expressed CD163 apart from CD1d. Molecular subtypes demonstrated statistical differences in CD163 expression, SHH-tumors were the most enriched (p = 0.006). Molecular and clinical subtypes of pediatric MB exhibit distinct differences in CD1d expression, which have important therapeutic implications. High CD1d expression in infantile MBs offers potential new immunotherapeutic treatment with NKT cell therapy in infants, where treatment is suboptimal due delayed radiotherapy. PMID- 25115740 TI - Profiling Hsp90 differential expression and the molecular effects of the Hsp90 inhibitor IPI-504 in high-grade glioma models. AB - Retaspimycin hydrochloride (IPI-504), an Hsp90 (heat shock protein 90) inhibitor, has shown activity in multiple preclinical cancer models, such as lung, breast and ovarian cancers. However, its biological effects in gliomas and normal brain derived cellular populations remain unknown. In this study, we profiled the expression pattern of Hsp90alpha/beta mRNA in stable glioma cell lines, multiple glioma-derived primary cultures and human neural stem/progenitor cells. The effects of IPI-504 on cell proliferation, apoptosis, motility and expression of Hsp90 client proteins were evaluated in glioma cell lines. In vivo activity of IPI-504 was investigated in subcutaneous glioma xenografts. Our results showed Hsp90alpha and Hsp90beta expression levels to be patient-specific, higher in high grade glioma-derived primary cells than in low-grade glioma-derived primary cells, and strongly correlated with CD133 expression and differentiation status of cells. Hsp90 inhibition by IPI-504 induced apoptosis, blocked migration and invasion, and significantly decreased epidermal growth factor receptor levels, mitogen-activated protein kinase and/or Akt activities, and secretion of vascular endothelial growth factor in glioma cell lines. In vivo study showed that IPI-504 could mildly attenuate tumor growth in immunocompromised mice. These findings suggest that targeting Hsp90 by IPI-504 has the potential to become an active therapeutic strategy in gliomas in a selective group of patients, but further research into combination therapies is still needed. PMID- 25115741 TI - Early development of congeneric sea urchins (Heliocidaris) with contrasting life history modes in a warming and high CO2 ocean. AB - The impacts of ocean change stressors - warming and acidification - on marine invertebrate development have emerged as a significant impact of global change. We investigated the response of early development to the larval stage in sympatric, congeneric sea urchins, Heliocidaris tuberculata and Heliocidaris erythrogramma with contrasting modes of development to ocean warming and acidification. Effects of these stressors were assessed by quantifying the percentage of normal development during the first 24 h post fertilization, in cross-factorial experiments that included three temperature treatments (control: 20 degrees C; +4: 24 degrees C; +6: 26 degrees C) and four pHNIST levels (control: 8.2; -0.4: 7.8; -0.6: 7.6; -0.8: 0.4). The experimental treatments were designed in context with present day and near-future (~2100) conditions for the southeast Australia global warming hotspot. Temperature was the most important factor affecting development of both species causing faster progression through developmental stages as well as a decrease in the percentage of normal development. H. erythrogramma embryos were less tolerant of increased temperature than those of H. tuberculata. Acidification impaired development to the larval stage in H. tuberculata, but this was not the case for H. erythrogramma. Thus, outcomes for the planktonic life phase of the two Heliocidaris species in response to ocean warming and acidification will differ. As shown for these species, single-stressor temperature or acidification studies can be misleading with respect to determining species' vulnerability and responses to global change. PMID- 25115742 TI - Editorial Comment from Dr Zampieri to Is the presence of varicocele associated with static and dynamic components of benign prostatic hyperplasia/lower urinary tract symptoms in elderly men? PMID- 25115743 TI - Sex is a stronger predictor of colorectal adenoma and advanced adenoma than fecal occult blood test. AB - Due to high costs and limited availability of screening colonoscopy, some screening programs require a positive fecal occult blood test (FOBT) before screening colonoscopy is remunerated. As male sex is a strong predictor of adenoma and advanced adenoma, we evaluated whether a positive FOBT or male sex is a stronger risk factor for adenoma and advanced adenoma. FOBT and screening colonoscopy results from 18.665 consecutive patients participating in a "national health check program" between 2009 and 2011 were included in this cohort study. Age-corrected adenoma detection rates (ADR), advanced adenoma detection rates (AADR) and carcinoma detection rates were calculated for men and women according to FOBT result separately. ADR and AADR in FOBT-positive men (34.6 and 11.8 %) and FOBT-negative men (29.1 and 7.6 %) were higher than ADR and AADR in FOBT positive women (20 and 6.9 %) and in FOBT-negative women (17.6 and 4.4 %), (p = 0.0003). Men with negative FOBT were at higher risk of having an adenoma and advanced adenoma than women with positive FOBT (p < 0.0001). Odds ratios of a positive FOBT for ADR and AADR were 1.3 (1.1-1.5) (p = 0.0047) and 1.6 (1.2-2.1) (p < 0.0001), respectively. Odds ratios of male sex to predict ADR and AADR were significantly higher with 1.9 (1.8-2.1) and 1.8 (1.6-2), respectively (p < 0.001). Male sex is a stronger predictor for colorectal adenoma and advanced adenoma than positive FOBT. These results should be taken into account analyzing FOBT-based screening programs. PMID- 25115744 TI - Use of "Real-World" data to describe adverse events during the treatment of metastatic renal cell carcinoma in routine clinical practice. AB - Insights into the experience of metastatic renal cell carcinoma (mRCC) patients are needed to optimize patient care. A retrospective, multicenter registry of mRCC patients treated at academic (Duke) and community (ACORN) practices was developed to fill this need. Treatment data were collected on 466 patients who received first-line therapy from 2007 to 2011. Clinically significant adverse events (AEs) were abstracted from medical records and compared to clinical trials. Two hundred and seventy patients received first-line therapy with sunitinib, 60 temsirolimus, 53 sorafenib, 25 pazopanib, and 58 "other." A total of 85.8 % of all patients experienced at least one AE: fatigue (56.7 %), vomiting (40.1 %), diarrhea (33.7 %), asthenia (32.8 %), and mucosal inflammation (20.8 %). When comparisons were made between patients >65 versus <65 years old, rates of AEs were higher in the younger group. Dosing approaches and timing of AEs during therapy were varied. These data shine light on the patient experience in routine practice versus structured clinical trials. Real-world AE frequency and severity differ from pivotal trials demonstrating the need to monitor patients closely and manage their AEs to optimize outcomes. As the number of treatment options with similar effectiveness grows, it is imperative to understand the real world patient experience. PMID- 25115746 TI - Physician's emerging roles relating to trends in health information technology. AB - Objective: To determine the new roles that physicians will adopt in the near future to adjust to accelerating trends from managed care to outcome-based practice to health care reform to health information technology to the evolving role of health consumers. Methods: Trends and related developments concerning the changing roles of physicians based on prior literature reviews. Results: Six possible roles, traditional, gatekeeper, coach, navigator, informatician and one voice among many, are discussed in terms of physician's centrality, patient autonomy, decision-making and uncertainty, information seeking, satisfaction and outcomes, particularly those related to compliance. Conclusion: A greater understanding of these emerging roles could lead to more efficacious outcomes in our ever changing, increasingly complex medical system. Patients often have little understanding of emerging trends that lead to the development of specialized roles such as hospitalist and navigators and, relatedly, the evolving roles of physicians. PMID- 25115745 TI - Effect of MLH1 -93G>A on gene expression in patients with colorectal cancer. AB - The DNA repair machinery plays a key role in maintaining genomic stability by preventing the emergence of mutations. Furthermore, the -93G>A polymorphism in the MLH1 gene has been associated with an increased risk of developing colorectal cancer. Therefore, the aim of this study was to examine the expression pattern and effect of this polymorphism in normal and tumour samples from patients with colorectal cancer. The MLH1 -93G>A (rs1800734) polymorphism was detected by PCR RFLP in 49 cases of colorectal cancer. MLH1 expression was investigated using real-time quantitative PCR. The results indicate a significant decrease in MLH1 expression in tumour samples compared to their normal counterparts. The MLH1 gene was also significantly repressed in samples from patients who had some degree of tumour invasion into other organs. Similarly, those patients who were in a more advanced tumour stage (TNM III and IV) exhibited a significant reduction in MLH1 gene expression. Finally, the mutant genotype AA of MLH1 was associated with a significant decrease in the expression of this gene. This finding suggests that this polymorphism could increase the risk of developing colorectal cancer by a defective mismatch repair system, particularly through the loss of MLH1 expression in an allele-specific manner. PMID- 25115747 TI - Effect of tele-emergency services on recruitment and retention of US rural physicians. AB - INTRODUCTION: As competition for physicians intensifies in the USA, rural areas are at a disadvantage due to challenges unique to rural medical practice. Telemedicine improves access to care not otherwise available in rural settings. Previous studies have found that telemedicine also has positive effects on the work environment, suggesting that telemedicine may improve rural physician recruitment and retention, although few have specifically examined this. METHODS: Using a mixed-method approach, clients of a single telemedicine service in the Upper Midwestern USA were surveyed and interviewed about their views of the impact of tele-emergency on physician recruitment and retention and the work environment. Surveys were completed by 292 clinical and administrative staff at 71 hospitals and semi-structured interviews were conducted with clinicians and administrators at 16 hospitals. RESULTS: Survey respondents agreed that tele emergency had a positive effect on physician recruitment and retention and related workplace factors. Interviewees elucidated how the presence of tele emergency played an important role in enhancing physician confidence, providing educational opportunities, easing burden, and supplementing care, workplace factors that interviewees believed would impact recruitment and retention. However, gains were limited by hospitals' interpretation of the Emergency Medical Treatment and Labor Act as requiring on-site physician coverage even if tele emergency was used. CONCLUSIONS: Results indicate that, all other factors being equal, tele-emergency increases the likelihood of physicians entering and remaining in rural practice. New regulatory guidance by the Centers for Medicare and Medicaid Services related to on-site physician coverage will likely accelerate implementation of tele-emergency services in rural hospitals. Telemedicine may prove to be an increasingly valuable recruitment and retention tool for rural hospitals as competition for physicians intensifies. PMID- 25115749 TI - Mortality study of civilian employees exposed to contaminated drinking water at USMC Base Camp Lejeune: a retrospective cohort study. AB - BACKGROUND: Two drinking water systems at U.S. Marine Corps Base Camp Lejeune, North Carolina were contaminated with solvents during 1950s-1985. METHODS: We conducted a retrospective cohort mortality study of 4,647 civilian, full-time workers employed at Camp Lejeune during 1973-1985 and potentially exposed to contaminated drinking water. We selected a comparison cohort of 4,690 Camp Pendleton workers employed during 1973-1985 and unexposed to contaminated drinking water. Mortality follow-up period was 1979-2008. Cause-specific standardized mortality ratios utilized U.S. age-, sex-, race-, and calendar period-specific mortality rates as reference. We used survival analysis to compare mortality rates between Camp Lejeune and Camp Pendleton workers and assess the effects of estimated cumulative contaminant exposures within the Camp Lejeune cohort. Ground water contaminant fate/transport and distribution system models provided monthly estimated contaminant levels in drinking water serving workplaces at Camp Lejeune. The confidence interval (CI) indicated precision of effect estimates. RESULTS: Compared to Camp Pendleton, Camp Lejeune workers had mortality hazard ratios (HRs) >1.50 for kidney cancer (HR = 1.92, 95% CI: 0.58, 6.34), leukemias (HR = 1.59, 95% CI: 0.66, 3.84), multiple myeloma (HR = 1.84, 95% CI: 0.45, 7.58), rectal cancer (HR = 1.65, 95% CI: 0.36, 7.44), oral cavity cancers (HR = 1.93, 95% CI: 0.34, 10.81), and Parkinson's disease (HR = 3.13, 95% CI: 0.76, 12.81). Within the Camp Lejeune cohort, monotonic exposure-response relationships were observed for leukemia and vinyl chloride and PCE, with mortality HRs at the high exposure category of 1.72 (95% CI: 0.33, 8.83) and 1.82 (95% CI: 0.36, 9.32), respectively. Cumulative exposures were above the median for most deaths from cancers of the kidney, esophagus, rectum, prostate, and Parkinson's disease, but small numbers precluded evaluation of exposure-response relationships. CONCLUSION: The study found elevated HRs in the Camp Lejeune cohort for several causes of death including cancers of the kidney, rectum, oral cavity, leukemias, multiple myeloma, and Parkinson's disease. Only 14% of the Camp Lejeune cohort died by end of follow-up, producing small numbers of cause specific deaths and wide CIs. Additional follow-up would be necessary to comprehensively assess drinking water exposure effects at the base. PMID- 25115760 TI - A Seeming Paradox: Ischemic Stroke in the Context of Idiopathic Thrombocytopenic Purpura. AB - Nowadays, we have a relatively sophisticated standard approach to a patient with acute ischemic stroke, including the sequence of diagnostic methods and treatment modalities. In practice, however, we are occasionally confronted with a patient whose medical history or comorbidities force us to make a decision without the support of guidelines. One such situation is the occurrence of acute ischemic stroke in a patient with known idiopathic thrombocytopenic purpura, where a tendency to use thrombolysis, anticoagulants, or antiplatelet agents collides with the fear of life-threatening bleeding. In this review, we try to outline current understanding of the pathophysiology of "paradoxical" ischemic events in this illness characterized by thrombocytopenia and to summarize clinical experience from case reports dealing with this topic, which could help us to rely on more than individual opinion seen through a purely "neurological" or "hematological" prism. PMID- 25115748 TI - Hippocampal volume mediates the relationship between measures of pre-treatment cocaine use and within-treatment cocaine abstinence. AB - BACKGROUND: Data suggest that the amygdala and hippocampus contribute to cocaine seeking and use, particularly following exposure to cocaine-related cues and contexts. Furthermore, indices of pre-treatment cocaine-use severity have been shown to correlate with treatment outcome in cocaine-dependent patients. METHODS: The aim of this study was to assess the relationships between amygdalar and hippocampal volumes and cocaine use before and during treatment. High-resolution magnetic-resonance brain images were obtained from 23 cocaine-dependent patients prior to treatment and 54 healthy comparison individuals. Automated segmentation of the amygdala and hippocampus images was performed in FreeSurfer. Cocaine dependent patients subsequently received behavioral therapy alone or combined with contingency management as part of a treatment trial, and cocaine-use indices (self-report, urine toxicology) were collected. RESULTS: Comparison participants and cocaine-dependent patients did not show significant difference in amygdalar and hippocampal volumes at pre-treatment. Within the patient group, greater hippocampal volumes were correlated with more days of cocaine use before treatment and with poorer treatment outcome as indexed by shorter durations of continuous abstinence from cocaine and lower percentages of cocaine-negative urine samples during treatment. Mediation analysis indicated that pre-treatment hippocampal volumes mediated the relationships between pre-treatment cocaine use and treatment outcomes. CONCLUSIONS: The finding of a significant correlation between hippocampal volume and pre-treatment cocaine-use severity and treatment response suggests that hippocampal volume should be considered when developing individualized treatments for cocaine dependence. PMID- 25115759 TI - Role of Nrf2/ARE pathway in protective effect of electroacupuncture against endotoxic shock-induced acute lung injury in rabbits. AB - NF-E2 related factor 2 (Nrf2) is a major transcription factor and acts as a key regulator of antioxidant genes to exogenous stimulations. The aim of current study was to determine whether Nrf2/ARE pathway is involved in the protective effect of electroacupuncture on the injured lung in a rabbit model of endotoxic shock. A dose of lipopolysaccharide (LPS) 5 mg/kg was administered intravenously to replicate the model of acute lung injury induced by endotoxic shock. Electroacupuncture pretreatment was handled bilaterally at Zusanli and Feishu acupoints for five consecutive days while sham electroacupuncture punctured at non-acupoints. Fourty anesthetized New England male rabbits were randomized into normal control group (group C), LPS group (group L), electroacupuncture + LPS group (group EL) and sham electroacupuncture + LPS (group SEL). At 6 h after LPS administration, the animals were sacrificed and the blood samples were collected for biochemical measurements. The lungs were removed for calculation of wet-to dry weight ratios (W/D), histopathologic examination, determination of heme oxygenase (HO)-1 protein and mRNA, Nrf2 total and nucleoprotein, as well as Nrf2 mRNA expression, and evaluation of the intracellular distribution of Nrf2 nucleoprotein. LPS caused extensive morphologic lung damage, which was lessened by electroacupuncture treatment. Besides, lung W/D ratios were significantly decreased, the level of malondialdehyde was inhibited, plasma levels of TNF-alpha and interleukin-6 were decreased, while the activities of superoxide dismutase, glutathione peroxidase and catalase were enhanced in the electroacupucnture treated animals. In addition, electroacupuncture stimulation distinctly increased the expressions of HO-1 and Nrf2 protein including Nrf2 total protein and nucleoprotein as well as mRNA in lung tissue, while these effects were blunted in the sham electroacupuncture group. We concluded that electroacupuncture treatment at ST36 and BL13 effectively attenuates lung injury in a rabbit model of endotoxic shock through activation of Nrf2/ARE pathway and following up regulation of HO-1 expression. PMID- 25115761 TI - Sustained release of tissue factor following thrombosis of lower limb trauma. AB - This study was undertaken to provide evidence for the mechanism of venous thromboembolism (VTE) in healthy patients with minor lower limb injury (fracture; Achilles tendon rupture) that was medically managed with plaster cast/brace immobilization. The Plaster Cast clinical trial provided a unique opportunity to identify the natural history of VTE using placebo-controlled patients (n = 183) with validation of the mechanism using the low-molecular-weight heparin (LMWH; reviparin)-treated patients (n = 182). Confirmed VTE in this population was associated with a burst of tissue factor release (and a minor fibrinolytic deficit) leading to thrombin generation that was sustained at least 5 weeks, greater with fractures than with soft-tissue injuries and greater with surgery than with conservative treatment. The root cause likely involves platelet/leukocyte activation (inflammation) rather than endothelial cell injury. Thromboprophylaxis with a low dose of LMWH reduced thrombin generation, with patients undergoing surgery benefitting the most. PMID- 25115762 TI - Oral anticoagulants and status of antidotes for the reversal of bleeding risk. AB - Anticoagulants have been used in clinical practice for more than 50 years. Their indications expand, as more people are diagnosed each year with atrial fibrillation and venous thromboembolism. Vitamin K antagonists have been the most popular choice due to their effectiveness and their ability to reverse bleeding using a known antidote; oral and intravenous vitamin K have long been known to reverse the effects of warfarin. With new classes of anticoagulants making their way onto the market, such as factor Xa inhibitors (rivaroxaban, apixaban) and direct thrombin inhibitors (dabigatran), the need for new reversal agents is paramount. Patients tend to be more receptive to these medications because they do not require routine blood monitoring, can be used at fixed doses, and do not have major drug or food interactions. Antidotes for these medications have shown promise in animal models and are currently in clinical trials. PMID- 25115763 TI - Oxidative Stress and Spontaneous Reperfusion of Infarct-Related Artery in Patients With ST-Segment Elevation Myocardial Infarction. AB - In the pathogenesis of atherosclerosis, oxidative stress plays a major role in plaque instability, rupture, and erosion, which subsequently leads to thrombus formation and causes total infarct-related artery (IRA) occlusion. We investigated the relationship between spontaneous reperfusion (SR) of IRA and oxidative stress in patients with anterior ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. A total of 341 consecutive patients with anterior STEMI were prospectively included in the present study. Patients were divided into 2 groups according to their thrombolysis in myocardial infarction (TIMI) flow grade: SR group (66 patients, TIMI flow 3) and non-SR group (275 patients, TIMI flow 0-2). On multivariate logistic regression analysis, oxidative stress index (beta = 0.868, 95% confidence interval [CI] = 0.806-0.934, P < .001), neutrophil to lymphocyte ratio, uric acid, mean platelet volume, Killip 2 to 4 class, and initial SYNTAX score were independently associated with SR. Oxidative stress as well as inflammation may play a pivotal role in the pathogenesis of SR in patients with STEMI. PMID- 25115764 TI - Dabigatran Versus Warfarin in Atrial Fibrillation: Multicenter Experience in Turkey. AB - Safety issues have been raised about dabigatran. We aimed to investigate the occurrence of safety outcomes in patients who had atrial fibrillation and a risk of stroke. We analyzed 439 patients prescribed dabigatran (n = 220) or warfarin (n = 219). Ischemic stroke occurred in 15 (6.8%) patients in the warfarin group versus 5 (5.2%) patients in the 110-mg group versus 1 (0.8%) patient in the 150 mg dabigatran group (P = .015). Intracranial hemorrhage occurred in 6 (2.7%) patients in the warfarin group versus 3 (2.4%) patients in the 150-mg dabigatran group (P = .104). Death from any cause occurred in 10 (4.6%) patients in the warfarin group versus 1 (1.0%) patient in the 110-mg dabigatran group (P = .005). Dabigatran was associated with less ischemic stroke and death from any cause than warfarin. Dabigatran may be a better option for stroke prophylaxis, where recommended monitoring with warfarin is suboptimal. PMID- 25115765 TI - High-resolution ultrasound allows percutaneous initiation and surveillance of prostate cancer in an orthotopic murine model. AB - INTRODUCTION: Prostate cancer xenografts should prefer orthotopic growth to subcutaneous tumors as the former more closely mimics the natural tumor environment. However, these models are technically demanding and require an invasive laparotomy. To overcome these problems, we evaluated a minimally invasive approach by performing percutaneous prostate puncture under the control of high-resolution ultrasound imaging. MATERIALS AND METHODS: Orthotopic tumor cell inoculation was performed in two groups of mice, i.e. in 10 nude mice via ultrasound-guided inoculation and in another 10 nude mice via an open surgical approach. Tumor growth was monitored after 4, 5 and 6 weeks by means of a high resolution ultrasound system. RESULTS: High-resolution ultrasound allowed exact tumor growth monitoring. After ultrasound-guided inoculation, 8 of 10 animals showed tumor engraftment. The surgical procedure was successful in 9 of 10 animals. Tumor volume was slightly but not significantly greater after surgical tumor induction. Our work demonstrates that tumor cell inoculation via percutaneous puncture of the prostate is feasible, less time-consuming and minimally invasive compared to an open surgical approach. This reduces the animal burden. CONCLUSION: Although the tumor size and the precision of inoculation is lower compared to the open surgical technique, this novel procedure enables real time prostate punctures, suggesting the feasibility of other procedures including biopsy and local drug applications. PMID- 25115767 TI - Robotics and regional anesthesia. AB - PURPOSE OF REVIEW: Robots in regional anesthesia are used as a tool to automate the performance of regional techniques reducing the anesthesiologist's workload and improving patient care. The purpose of this review is to show the latest findings in robotic regional anesthesia. RECENT FINDINGS: The literature separates robots in anesthesia into two groups: pharmacological robots and manual robots. Pharmacological robots are mainly closed-loop systems that help in the titration of anesthetic drugs to patients undergoing surgery. Manual robots are mechanical robots that are used to support or replace the manual gestures performed by anesthesiologists. Although in the last decade researchers have focused on the development of decision support systems and closed-loop systems, more recent evidence supports the concept that robots can also be useful in performing regional anesthesia techniques. SUMMARY: Robots can improve the performance and safety in regional anesthesia. In this review, we present the developments made in robotic and automated regional anesthesia, and discuss the current state of research in this field. PMID- 25115766 TI - Postoperative ICU management of patients after subarachnoid hemorrhage. AB - PURPOSE OF REVIEW: This article reviews recent advances in the postoperative ICU management of patients after subarachnoid hemorrhage (SAH), especially with regards to hemodynamic management, methods of improving neurological outcomes, and management of cardiac and pulmonary complications. RECENT FINDINGS: Several hemodynamic monitors and parameters may be useful for guiding volume therapy, including cardiac output, stroke volume variation monitoring, and global end diastolic volume index. Early goal-directed hemodynamic therapy after SAH has recently been shown to improve clinical outcomes in patients with a poor clinical grade or coexisting cardiopulmonary complications. Recent laboratory and imaging modalities are being developed to identify patients at risk for developing vasospasm after SAH. Evidence for the use of various prophylactic adjuvant therapies to prevent vasospasm, including magnesium, phosphodiesterase 3 inhibitors, and therapeutic hypothermia, is emerging. Intrathecal administration of vasodilators or fibrinolytics may have offered advantages over systemic drug administration in the treatment of vasospasm. Pulmonary and cardiac complications are common after SAH, and are associated with an increased risk of mortality. SUMMARY: The postoperative ICU period after SAH is associated with a significant morbidity and mortality risk, and recent studies have greatly contributed to our understanding of how to optimally manage these patients. PMID- 25115768 TI - Bioactive constituents from Croton sparsiflorus Morong. AB - Whole plant extracts of Croton sparsiflorus in methanol have shown significant enzyme inhibition and antioxidant activities. Bioassay-guided isolation of chloroform fraction at pH 3 resulted in the identification of crotsparinine (1) and crotsparine (2), while sparsiflorine (3) was purified from the chloroform fraction at pH 9. The structures of the compounds were confirmed through spectral analyses (EI-MS, (1)H and (13)C NMR). The isolated compounds 1-3 exhibited remarkable enzyme inhibition activity with IC50 values 27.01 +/- 1.1, 22.26 +/- 1.0 and 18.02 +/- 1.3 MUM in xanthine oxidase and 48.42 +/- 1.5, 48.05 +/- 1.4 and 7.42 +/- 1.0 MUM in acetylcholine esterase assays, respectively. These compounds also showed potent radical scavenging and reducing properties in DPPH and FRAP assays, respectively. The present results suggest the validity of the traditional uses of C. sparsiflorus in rheumatism and gout. Furthermore, the isolated noraporphine alkaloids can be useful in the treatment of neurodegenerative diseases. PMID- 25115769 TI - Echocardiographic factors discriminating biventricular versus univentricular approach in the foetus with borderline left ventricle. AB - BACKGROUND: The term "borderline left ventricle" describes a small left heart that may be inadequate to provide systemic cardiac output and implies the potential need for a single-ventricle palliation. The aim of this study was to identify foetal echocardiographic features that help discriminate which infants will undergo single-ventricle palliation versus biventricular repair to aid in prenatal counselling. METHODS: The foetal database at our institution was searched to identify all foetuses with borderline left ventricle, as determined subjectively by a foetal cardiologist, from 2000 to 2011. The foetal images were retrospectively analysed for morphologic and physiologic features to determine which best predicted the postnatal surgical choice. RESULTS: Of 39 foetuses identified with borderline left ventricle, 15 were planned for a univentricular approach, and 24 were planned for a biventricular approach. There were significant differences between the two outcome groups in the Z-scores of the mitral valve annulus, left ventricular end-diastolic dimension, aortic valve annulus, and ascending aorta diameter (p<0.05). With respect to discriminating univentricular outcomes, cut-offs of mitral valve Z-score ?-1.9 and tricuspid:mitral valve ratio ?1.5 were extremely sensitive (100%), whereas a right:left ventricular end-diastolic dimension ratio ?2.1 provided the highest specificity (95.8%). CONCLUSION: In foetuses with borderline left ventricle, a mitral valve Z-score ?-1.9 or a tricuspid:mitral valve ratio ?1.5 suggests a high probability of biventricular repair, whereas a right:left ventricular end diastolic dimension ratio ?2.1 confers a likelihood of single-ventricle palliation. PMID- 25115770 TI - Draft genome sequences of three Holospora species (Holospora obtusa, Holospora undulata, and Holospora elegans), endonuclear symbiotic bacteria of the ciliate Paramecium caudatum. AB - We present draft genome sequences of three Holospora species, hosted by the ciliate Paramecium caudatum; that is, the macronucleus-specific H. obtusa and the micronucleus-specific H. undulata and H. elegans. We investigate functions of orthologous core genes conserved across the three Holospora species, which may be essential for the infection and survival in the host nucleus. PMID- 25115771 TI - Lamina cribrosa displacement after optic nerve sheath fenestration in idiopathic intracranial hypertension: a new tool for monitoring changes in intracranial pressure? PMID- 25115772 TI - The effect of glucagon-like peptide-1 in the management of diabetes mellitus: cellular and molecular mechanisms. AB - Incretins, such as glucagon-like peptide-1 (GLP)-1, have been shown to elevate plasma insulin concentration. The purpose of this study is to investigate the cellular and molecular basis of the beneficial effects of GLP-1. Normal and diabetic male Wistar rats were treated with GLP-1 (50 ng/kg body weight) for 10 weeks. At the end of the experiment, pancreatic tissues were taken for immunohistochemistry, immunoelectron microscopy and real-time polymerase chain reaction studies. Samples of blood were retrieved from the animals for the measurement of enzymes and insulin. The results show that treatment of diabetic rats with GLP-1 caused significant (P < 0.05) reduction in body weight gain and blood glucose level. GLP-1 (10(-12)-10(-6) M) induced significant (P < 0.01) dose dependent increases in insulin release from the pancreas of normal and diabetic rats compared to basal. Diabetes-induced abnormal liver (aspartate aminotransferase and alanine aminotransferase) and kidney (blood urea nitrogen and uric acid) parameters were corrected in GLP-1-treated rats compared to controls. GLP-1 treatment induced significant (P < 0.05) elevation in the expression of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione peroxidase, insulin receptor and GLP-1-receptor genes in diabetic animals compared to controls. GLP-1 is present in pancreatic beta cells and significantly (P < 0.05) increased the number of insulin-, glutathione reductase- and catalase immunoreactive islet cells. The results of this study show that GLP-1 is co localized with insulin and seems to exert its beneficial effects by increasing cellular concentrations of endogenous antioxidant genes and other genes involved in the maintenance of pancreatic beta cell structure and function. PMID- 25115773 TI - Effects of sildenafil on nanostructural and nanomechanical changes in mitochondria in an ischaemia-reperfusion rat model. AB - Sildenafil exerts cardioprotective effects by activating the opening of mitochondrial ATP-sensitive potassium channels to attenuate ischaemia-reperfusion (IR) injury. In the present study, we used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties to assess sildenafil-mediated cardioprotection in a rat myocardial infarction model. To investigate the cardioprotective effects of sildenafil, we used an in vivo Sprague-Dawley rat model of IR. Rats were randomly divided into three groups: (i) sham-operated rats (control; n = 5); (ii) IR-injured rats treated with vehicle (normal saline; IR; n = 10); and (iii) IR-injured rats treated with 0.75 mg/kg, i.p., sildenafil (IR + Sil; n = 10). Morphological and mechanical changes to mitochondria were analysed by AFM. Infarct areas were significantly reduced in sildenafil-treated rats (7.8 +/- 3.9% vs 20.4 +/- 7.0% in the sildenafil-treated and untreated IR groups, respectively; relative reduction 62%; P < 0.001). Analysis of mitochondria by AFM showed that IR injury significantly increased the areas of isolated mitochondria compared with control (24 150 +/- 18 289 vs 1495 +/- 1139 nm(2) , respectively; P < 0.001), indicative of mitochondrial swelling. Pretreatment with sildenafil before IR injury reduced the mitochondrial areas (7428 +/- 3682 nm(2) ; P < 0.001; relative reduction 69.2% compared with the IR group) and ameliorated the adhesion force of mitochondrial surfaces. Together, these results suggest that sildenafil has cardioprotective effects against IR injury in a rat model by improving the morphological and mechanical characteristics of mitochondria. PMID- 25115774 TI - GFP stable transfection facilitated the characterization of lung cancer stem cells. AB - Cancer stem cells (CSCs) are a subset of cancer cells that play key roles in metastasis and cancer relapse. The elimination of CSCs is very important during cancer therapy. To develop drugs that target CSCs, the isolation and identification of putative CSCs are required. Some of the characteristics of CSCs are assessed by cell survival assays. In such experiments, the density of the cells seeded on the plates may affect the experimental results, leading to potentially inaccurate conclusions. In this study, a new assay to facilitate the characterization of CSCs has been developed by stable transfection of GFP, using the A549 lung cancer cell line as a model. A putative CSC line, A549 sphere cells, was obtained by culturing A549 cells in ultra-low dishes in serum-free medium. To ensure that the putative CSCs were grown under the same conditions as the A549-GFP cells and were not affected by the number of cells seeded, A549 sphere cells were mixed with GFP stably transfected A549 (A549-GFP) cells. The mixture was subjected to flow cytometry assay and inverted fluorescence microscopy to detect changes in the proportion of GFP-positive cells after treatment. A549 sphere cells had a slower proliferation rate and an improved chemoresistance. They also showed differentiation ability. This work suggests that mixing GFP stably transfected cancer cells with putative CSCs may facilitate the identification of CSCs, making it convenient for studies of targeted CSCs. PMID- 25115776 TI - Hydrogen bond mediated aglycone delivery: synthesis of linear and branched alpha glucans. AB - A Hydrogen bond mediated aglycone delivery (HAD) method was applied to the synthesis of alpha-glucans, which are abundant in nature, but as targets represent a notable challenge to chemists. The synthesis of linear oligosaccharide sequences was accomplished in complete stereoselectivity in all glycosylations. The efficacy of HAD may diminish with the increased bulk of the glycosyl acceptor, and may be an important factor for the syntheses of oligomers beyond pentasaccharides. The synthesis of a branched structure proved more challenging, particularly with bulky trisaccharide acceptors. PMID- 25115777 TI - On-line SERS detection of single bacterium using novel SERS nanoprobes and a microfluidic dielectrophoresis device. AB - The integration of novel surface-enhanced Raman scattering (SERS) nanoprobes and a microfluidic dielectrophoresis (DEP) device is developed for rapid on-line SERS detection of Salmonella enterica serotype Choleraesuis and Neisseria lactamica. The SERS nanoprobes are prepared by immobilization of specific antibody onto the surface of nanoaggregate-embedded beads (NAEBs), which are silica-coated, dye induced aggregates of a small number of gold nanoparticles (AuNPs). Each NAEB gives highly enhanced Raman signals owing to the presence of well-defined plasmonic hot spots at junctions between AuNPs. Herein, the on-line SERS detection and accurate identification of suspended bacteria with a detection capability down to a single bacterium has been realized by the NAEB-DEP-Raman spectroscopy biosensing strategy. The practical detection limit with a measurement time of 10 min is estimated to be 70 CFU mL(-1) . In comparison with whole-cell enzyme-linked immunosorbent assay (ELISA), the SERS-nanoprobe-based biosensing method provides advantages of higher sensitivity and requiring lower amount of antibody in the assay (100-fold less). The total assay time including sample pretreatment is less than 2 h. Hence, this sensing strategy is promising for faster and effective on-line multiplex detection of single pathogenic bacterium by using different bioconjugated SERS nanoprobes. PMID- 25115775 TI - Association between CYP1A2 and CYP1B1 polymorphisms and colorectal cancer risk: a meta-analysis. AB - BACKGROUND: The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study is to evaluate the role of CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly genotypes in colorectal cancer susceptibility. We performed a meta-analysis on all the eligible studies that provided 5,817 cases and 6,544 controls for CYP1A2*F (from 13 studies), 9219 cases and 10406 controls for CYP1B1 Leu432Val (from 12 studies), 6840 cases and 7761 controls for CYP1B1 Asn453Ser (from 8 studies), and 4302 cases and 4791 controls for CYP1B1Arg48Gly (from 6 studies). Overall, no significant association was found between CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly and colorectal cancer risk when all the eligible studies were pooled into the meta analysis. And in the subgroup by ethnicity and source of controls, no evidence of significant association was observed in any subgroup analysis. CONCLUSIONS/SIGNIFICANCE: In summary, this meta-analysis indicates that CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly polymorphisms do not support an association with colorectal cancer, and further studies are needed to investigate the association. In addition, our work also points out the importance of new studies for CYP1A2*F polymorphism in Asians, because high heterogeneity was found (dominant model: I(2) = 81.3%; heterozygote model: I(2) = 79.0). PMID- 25115778 TI - Short bowel syndrome and clopidogrel non-responsiveness: a new indication for platelet aggregometry? PMID- 25115779 TI - Asymptomatic coronary artery spasm with acute pathological ST elevation on routine ECG: is it common? AB - Asymptomatic spontaneous coronary artery spasm is rare and there are no case reports in literature presenting with acute ST elevation on routine ECG. We present the case of a 68-year-old Caucasian man who presented to a primary care physician for a routine ECG as part of hypertension follow-up. ECG revealed ST elevation in inferior leads II, III and aVF with reciprocal ST depression in leads I, aVL and also ST depression in anterior leads V1, V2 and V3 suggesting ongoing inferoposterior ST elevation myocardial infarction. The patient was completely well, stable and asymptomatic and he was rushed immediately to the coronary care unit via emergency ambulance. The patient was subjected to a battery of urgent investigations which were all normal. Also an urgent coronary angiogram was undertaken which showed completely normal coronary anatomy. PMID- 25115780 TI - Completely calcified non-functioning kidney: a classical image of putty kidney. PMID- 25115781 TI - Beneficial effects of growth hormone therapy for ossification defects after bone distraction in X linked hypophosphataemic rickets. AB - A report on two homozygous twin girls affected by X linked hypophosphataemic rickets. They were examined due to short stature and genu varum of both tibias. They were treated with calcitriol and Joulie's solution, whereon it was observed that serum parathyroid hormone and phosphaturia decreased while phosphataemia increased. They underwent a tibial osteotomy (by means of the insertion of Kirchner needles) at 7.7 years of age for correction of genu varum and a normal consolidation was reached 1 month later. Nonetheless, height was percentile <1 after menarche, so both sisters asked for bone lengthening. Because of this, at 15 years of age femoral distraction was performed, but no bone callus was observed 14 months later. Consequently, they were treated with subcutaneous growth hormone, showing bone callus at 6 months. Finally, the external fixators were removed due to ossification in the lengthened segments. PMID- 25115784 TI - Bilateral extraocular muscle (EOM) metastases from adenocarcinoma of the gastro oesophageal junction (GOJ). PMID- 25115783 TI - Methaemoglobinaemia in a G6PD-deficient child treated with rasburicase. AB - A 5-year-old boy from the Congo, was admitted for hyperleucocytic acute lymphoblastic leukaemia, with a high risk of tumour lysis syndrome (TLS). He had splenomegaly and mediastinal lymphadenopathy on chest X-ray. We started steroids and hyperhydration with rasburicase to prevent TLS. Respiratory failure with mediastinal enlargement developed rapidly. A few hours after intensive care unit (ICU) admission, he was started on mechanical ventilation. Chemotherapy was started immediately given the strong suspicion of mediastinal compression. Low oxygen saturation with high partial arterial oxygen pressure persisted. Blood tests confirmed 20% methaemoglobinaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Allopurinol was substituted for rasburicase. The methaemoglobinaemia disappeared rapidly and he was discharged from the ICU after 72 h. In case of rasburicase use, a close clinical monitoring is mandatory, especially in populations where G6PD deficiency is highly prevalent. Methaemoglobinaemia must be suspected in case of low oxygen saturation when all other potential causes have been ruled out. PMID- 25115782 TI - Severe agitation in depression precipitated by dasatinib. AB - We describe a case of a man with chronic myeloid leukaemia who achieved remission through dasatinib therapy after being unable to tolerate several tyrosine kinase inhibitor (TKI) regimens due to severe physical side effects. However, this coincided with the onset of distressing agitation, insomnia and motor restlessness leading him to take a large zopiclone overdose. Start of appropriate therapy with a clonazepam, venlafaxine and mirtazapine combination led to a rapid improvement in symptomatology. We discuss the differential diagnosis and review the literature of neuropsychiatric complications of TKIs. This case serves as an illustrative reminder that in cases of complicated agitation referral to specialist mental health teams for rational psychopharmacological management is advised. PMID- 25115785 TI - Kasabach-Merritt phenomenon in a neonatal kaposiform haemangioendothelioma. PMID- 25115786 TI - Dissemination of plasmid-encoded AmpC beta-lactamases in antimicrobial resistant Salmonella serotypes originating from humans, pigs and the swine environment. AB - The aim of this study was to characterize and determine the inter-serovar exchange of AmpC beta-lactamase conferring plasmids isolated from humans, pigs and the swine environment. Plasmids isolated from a total of 21 antimicrobial resistant (AMR) Salmonella isolates representing human clinical cases (n=6), pigs (n=6) and the swine farm environment (n=9) were characterized by replicon typing and restriction digestion, inter-serovar transferability by conjugation, and presence of AmpC beta-lactamase enzyme encoding gene blaCMY-2 by southern hybridization. Based on replicon typing, the majority (17/21, 81%) of the plasmids belonged to the I1-Igamma Inc group and were between 70 and 103kb. The potential for inter-serovar plasmid transfer was further confirmed by the PCR detection of AMR genes on the plasmids isolated from trans-conjugants. Plasmids from Salmonella serovars Anatum, Ouakam, Johannesburg and Typhimurium isolated from the same cohort of pigs and their environment and S. Heidelberg from a single human clinical isolate had identical plasmids based on digestion with multiple restriction enzymes (EcoRI, HindIII and PstI) and southern blotting. We demonstrated likely horizontal inter-serovar exchange of plasmid-encoding AmpC beta-lactamases resistance among MDR Salmonella serotypes isolated from pigs, swine farm environment and clinical human cases. This study provides valuable information on the role of the swine farm environment and by extension other livestock farm environments, as a potential reservoir of resistant bacterial strains that potentially transmit resistance determinants to livestock, in this case, swine, humans and possibly other hosts by horizontal exchange of plasmids. PMID- 25115787 TI - Identification and typing of Brucella spp. in stranded harbour porpoises (Phocoena phocoena) on the Dutch coast. AB - The presence of Brucella (B.) spp. in harbour porpoises stranded between 2008 and 2011 along the Dutch coast was studied. A selection of 265 tissue samples from 112 animals was analysed using conventional and molecular methods. In total, 4.5% (5/112) of the animals corresponding with 2.3% (6/265) Brucella positive tissue samples were Brucella positive by culture and these were all confirmed by real time polymerase chain reaction (real-time PCR) based on the insertion element 711 (IS711). In addition, two more Brucella-positive tissue samples from two animals collected in 2011 were identified using real-time PCR resulting in an overall Brucella prevalence of 6.3% (7/112 animals). Brucella spp. were obtained from lungs (n=3), pulmonary lymph node (n=3) and lungworms (n=2). Multi Locus Variable Number of Tandem Repeats (VNTR) Analysis (MLVA) typing based on the MLVA-16 showed that the Brucella isolates were B. ceti. Additional in silico Multi Locus Sequence typing (MLST) after whole genome sequencing of the 6 Brucella isolates confirmed B. ceti ST 23. According to the Brucella 2010 MLVA database, the isolated Brucella strains encountered were of five genotypes, in two distinct subclusters divided in two different time periods of harbour porpoises collection. This study is the first population based analyses for Brucella spp. infections in cetaceans stranded along the Dutch coast. PMID- 25115788 TI - The effect of hyaluronic acid functionalized carbon nanotubes loaded with salinomycin on gastric cancer stem cells. AB - Gastric cancer stem cells (CSCs) play a crucial role in the initiation, development, relapse and metastasis of gastric cancer because they are resistant to a standard chemotherapy and the residual CSCs are able to proliferate indefinitely. Therefore, eradication of this cell population is a primary objective in gastric cancer therapy. Here, we report a gastric CSCs-specifically targeting drug delivery system (SAL-SWNT-CHI-HA complexes) based on chitosan(CHI) coated single wall carbon nanotubes (SWNTs) loaded with salinomycin (SAL) functionalized with hyaluronic acid (HA) can selectively eliminate gastric CSCs. Gastric CSCs were identified as CD44+ cells and cultured in serum-free medium. SAL-SWNT-CHI-HA complexes were capable of inhibiting the self-renewal capacity of CD44+ population, and decrease mammosphere- and colon-formation of CSCs. In addition, the migration and invasion of gastric CSCs were significantly blocked by SAL-SWNT-CHI-HA complexes. Quantitative and qualitative analysis of cellular uptake demonstrated that HA functionalization facilitated the uptake of SWNTs in gastric CSCs while free HA competitively inhibited cellular uptake of SAL-SWNT CHI-HA delivery system, revealing the mechanism of CD44 receptor-mediated endocytosis. The SAL-SWNT-CHI-HA complexes showed the strongest antitumor efficacy in gastric CSCs by inducing apoptosis, and in CSCs mammospheres by penetrating deeply into the core. Taken altogether, our studies demonstrated that this gastric CSCs-targeted SAL-SWNT-CHI-HA complexes would provide a potential strategy to selectively target and efficiently eradicate gastric CSCs, which is promising to overcome the recurrence and metastasis of gastric cancer and improve gastric cancer treatment. PMID- 25115789 TI - Collagen mimetic peptide engineered M13 bacteriophage for collagen targeting and imaging in cancer. AB - Collagens are over-expressed in various human cancers and subsequently degraded and denatured by proteolytic enzymes, thus making them a target for diagnostics and therapeutics. Genetically engineered bacteriophage (phage) is a promising candidate for the development of imaging or therapeutic materials for cancer collagen targeting due to its promising structural features. We genetically engineered M13 phages with two functional peptides, collagen mimetic peptide and streptavidin binding peptide, on their minor and major coat proteins, respectively. The resulting engineered phage functions as a therapeutic or imaging material to target degraded and denatured collagens in cancerous tissues. We demonstrated that the engineered phages are able to target and label abnormal collagens expressed on A549 human lung adenocarcinoma cells after the conjugation with streptavidin-linked fluorescent agents. Our engineered collagen binding phage could be a useful platform for abnormal collagen imaging and drug delivery in various collagen-related diseases. PMID- 25115790 TI - Effects of two different rearing protocols for Holstein bull calves in the first 3 weeks of life on health status, metabolism and subsequent performance. AB - The aim of this study was to investigate the impact of weight gain of calves within the first 3 weeks of life on health status and subsequent performance. Holstein bull calves were reared either intensively (IR; individual hutches and ad libitum milk feeding for the first 3 weeks of life; n = 24), or according to the established protocol [ER; 4 l milk/day in hutches during week 1 and 720 g/day milk replacer (MR) from day 8 to 21 in a group pen; n = 24]. Water, hay and concentrates were freely available to all calves. From week 4, calves of both groups were housed together in a group pen and fed 720 g MR/day; step-down weaning was performed between week 5 and 10. Key metabolic blood parameters were analysed on day 2, 12, 21 and 70 of life. After weaning, all animals were fed concentrates and corn silage until slaughter at an age of 8 months. Within the first 3 weeks, average daily weight gain was threefold higher in IR calves in relation to ER calves (1.28 vs. 0.38 kg/day, p < 0.001). Neither incidence nor duration of scouring differed significantly between groups. Starter intake (week 4-10) was higher in IR calves in relation to ER calves (49.7 vs. 38.0 kg/calf, p = 0.006). Serum glucose, urea, albumin and insulin were higher at an age of 21 days in IR calves in relation to ER calves; no differences were obvious at an age of 70 days. Plasma GH and IGF-I concentrations revealed an uncoupling of the somatotropic axis in ER calves within the first 3 weeks of life. At slaughter, body weight of IR calves tended to be higher than that of the ER calves (320 vs. 309 kg, p = 0.07). In conclusion, intensive feeding and individual housing during the first 3 weeks of life had positive long-term effects on subsequent performance. PMID- 25115791 TI - Social participation of school-aged children who use communication aids: the views of children and parents. AB - Social participation is crucial for children's development and well-being; however, little is known about the social participation of children who use communication aids. This article presents findings from interviews with eight 5- to 14-year-old children who used communication aids and their parents about social participation, communicative interactions, and peer relationships. Video- and audio-recordings were transcribed and analyzed using thematic content analysis, and five themes were identified. Two themes reflect parents' views: Communication partners and strategies and Access to aided communication. Three themes reflect perceptions expressed both by children and parents: Participation in society, Interaction opportunities, and Social relationships. The findings provide insights into both the achievements and the challenges experienced by young people who use aided communication. PMID- 25115794 TI - Two new cyclic dipeptides from Rhinocladiella sp. lgt-3, a fungal endophyte isolated from Tripterygium wilfordii Hook. AB - Two new cyclic dipeptides, rhinocladin A (1) and rhinocladin B (2), were isolated from a fungal endophyte (Rhinocladiella sp. lgt-3) of Tripterygium wilfordii Hook. Their structures were elucidated by 1D and 2D NMR spectra. The monoamine oxidase inhibitory activity of 1 and 2 was also evaluated. PMID- 25115795 TI - Fermented food in the context of a healthy diet: how to produce novel functional foods? AB - PURPOSE OF REVIEW: This review presents an overview of recent studies on the production of functional fermented foods, of both traditional and innovative natures, and the mapping of the functional compounds involved. RECENT FINDINGS: The functional aspects of fermented foods are mostly related to the concept of probiotic bacteria or the targeted microbial generation of functional molecules, such as bioactive peptides, during food fermentation. Apart from conventional yoghurt and fermented milks, several fermented nondairy foods are globally gaining in interest, in particular from soy or cereal origin, sometimes novel but often originating from ethnic (Asian) diets. In addition, a range of functional nonmicrobial compounds may be added to the fermented food matrix. Overall, a wide variety of potential health benefits is being claimed, yet often poorly supported by mechanistic insights and rarely demonstrated with clinical trials or even animal models. SUMMARY: Although functional foods offer considerable market potential, several issues still need to be addressed. As most of the studies on functional fermented foods are of a rather descriptive and preliminary nature, there is a clear need for mechanistic studies and well controlled in-vivo experiments. PMID- 25115793 TI - The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that promotes peritoneal metastasis. AB - BACKGROUND: Ovarian cancer (OCa) peritoneal metastasis is the leading cause of cancer-related deaths in women with limited therapeutic options available for treating it and poor prognosis, as the underlying mechanism is not fully understood. METHOD: The clinicopathological correlation of G9a expression was assessed in tumor specimens of ovarian cancer patients. Knockdown or overexpression of G9a in ovarian cancer cell lines was analysed with regard to its effect on adhesion, migration, invasion and anoikis-resistance. In vivo biological functions of G9a were tested by i.p. xenograft ovarian cancer models. Microarray and quantitative RT-PCR were used to analyze G9a-regulated downstream target genes. RESULTS: We found that the expression of histone methyltransferase G9a was highly correlated with late stage, high grade, and serous-type OCa. Higher G9a expression predicted a shorter survival in ovarian cancer patients. Furthermore, G9a expression was higher in metastatic lesions compared with their corresponding ovarian primary tumors. Knockdown of G9a expression suppressed prometastatic cellular activities including adhesion, migration, invasion and anoikis-resistance of ovarian cancer cell lines, while G9a over-expression promoted these cellular properties. G9a depletion significantly attenuated the development of ascites and tumor nodules in a peritoneal dissemination model. Importantly, microarray and quantitative RT-PCR analysis revealed that G9a regulates a cohort of tumor suppressor genes including CDH1, DUSP5, SPRY4, and PPP1R15A in ovarian cancer. Expression of these genes was also inversely correlated with G9a expression in OCa specimens. CONCLUSION: We propose that G9a contributes to multiple steps of ovarian cancer metastasis and represents a novel target to combat this deadly disease. PMID- 25115796 TI - Vocal behavior and vocal central pattern generator organization diverge among toadfishes. AB - Among fishes, acoustic communication is best studied in toadfishes, a single order and family that includes species commonly known as toadfish and midshipman. However, there is a lack of comparative anatomical and physiological studies, making it difficult to identify both shared and derived mechanisms of vocalization among toadfishes. Here, vocal nerve labeling and intracellular in vivo recording and staining delineated the hindbrain vocal network of the Gulf toadfish Opsanus beta. Dextran-biotin labeling of the vocal nerve or intracellular neurobiotin fills of motoneurons delineated a midline vocal motor nucleus (VMN). Motoneurons showed bilaterally extensive dendritic arbors both within and lateral to the paired motor nuclei. The motoneuron activity matched that of the spike-like vocal nerve motor volley that determines the natural call duration and frequency. Ipsilateral vocal nerve labeling with biocytin or neurobiotin yielded dense bilateral transneuronal filling of motoneurons and coextensive columns of premotor neurons. These premotor neurons generated pacemaker-like action potentials matched 1:1 with vocal nerve and motoneuron firing. Transneuronal transport further revealed connectivity within and between the pacemaker-motor circuit and a rostral prepacemaker nucleus. Unlike the pacemaker-motor circuit, prepacemaker firing did not match the frequency of vocal nerve activity but instead was predictive of the duration of the vocal nerve volley that codes for call duration. Transneuronally labeled terminal-like boutons also occurred in auditory-recipient hindbrain nuclei, including neurons innervating the inner ear and lateral line organs. Together with studies of midshipman, we propose that separate premotor populations coding vocal frequency and duration with direct premotor coupling to auditory-lateral line nuclei are plesiomorphic characters for toadfishes. Unlike in midshipman, transneuronal labeling in toadfishes reveals an expansive column of pacemaker neurons that is weakly coupled to prepacemaker neurons, a character that likely depends on the extent of gap junction coupling. We propose that these and other anatomical characters contribute to neurophysiological properties that, in turn, sculpt the species-typical patterning of frequency and amplitude-modulated vocalizations. PMID- 25115797 TI - Anthropometry and body composition of vertically HIV-infected children and adolescents under therapy with and without protease inhibitors. AB - OBJECTIVE: Although the benefits of highly active antiretroviral therapy (HAART) have been documented, it is thought to be associated to disturbances in nutritional status. These disturbances may occur early in life and are poorly understood. The present study aimed to investigate the relationship between anthropometric parameters and body composition of perinatally HIV-infected children and adolescents under HAART, according to use and non-use of protease inhibitors. DESIGN: Cross-sectional study undertaken between August and December 2007. Demographic, socio-economic, clinical and anthropometric data were collected from the patients. The chi 2 test, Wilcoxon rank sum test (Mann Whitney) and t test were used to compare the following variables between users and non-users of protease inhibitors: age, gender, per capita income, HAART exposure, antiretroviral therapy adopted in the last three years, CD4 count, viral load, pubertal stage, nutritional status (BMI-for-age, height-for-age, waist and neck circumferences, triceps skinfold thickness, body fat percentage, upper-arm fat area and upper-arm muscle area). SETTING: An HIV/AIDS out-patient clinic, Sao Paulo, Brazil. SUBJECTS: One hundred and fifteen patients (children and adolescents aged 6-19 years). RESULTS: Protease inhibitors users had a higher prevalence of stunting (P=0.03), lower BMI (P=0.03) and lower percentage of body fat (P=0.05) compared with non-users. There was no statistically significant difference between the HAART regimens and measurements of fat adiposity. CONCLUSIONS: The findings of the study suggest that children and adolescents under protease inhibitors are at higher risk of growth and development deviations, but not at risk of body fat redistribution. PMID- 25115798 TI - Occurrence of Treponema DNA in equine hoof canker and normal hoof tissue. AB - REASONS FOR PERFORMING STUDY: Equine hoof canker is a chronic pododermatitis of still unknown aetiology. Recent findings reported for 3 canker-bearing individuals are suggestive for Treponema spp. having a role in disease pathogenesis. OBJECTIVES: Based on this hypothesised association, we assessed a larger number of DNA samples from hooves with canker and normal hooves for the presence of treponemal DNA. STUDY DESIGN: Retrospective survey of archived material. METHODS: The study involved 71 archival, PCR-compatible DNA extractions purified from 59 canker samples obtained from 26 equine cases and from 12 hoof biopsies taken from 9 canker-free control horses. Presence of treponemal DNA was assessed by qualitative PCR using 4 different primer pairs recognising in sum a broad range of Treponema ssp. Obtained amplification products were identified by bidirectional sequencing and BLAST alignment. RESULTS: Treponemal DNA was detected in 37 of 59 canker DNA samples from 19 of 26 cases and in 9 of 12 hoof DNA samples from 7 of 9 healthy individuals. Canine oral Treponema sp. and Treponema medium ssp. bovis were the most frequently detected treponemal sequences in hoof canker, while control tissues were mainly shown to harbour Treponema refringens-like or canine oral Treponema-like DNA. All control samples tested negative for T. medium ssp. bovis DNA. CONCLUSIONS: Treponema DNA was detectable in the majority of hoof canker and control samples. The sample groups differed to some extent regarding identified Treponema phylotypes; however, this finding may be explained by the methodology used. Treponemes that are highly similar to bovine digital dermatitis treponemes are present in canker lesions. However, further work is needed to clarify the specific contribution of the identified Treponema phylotypes to the pathogenesis of disease. PMID- 25115799 TI - Aerobic denitrification by Pseudomonas stutzeri C3 incapable of heterotrophic nitrification. AB - An aerobic denitrifier was isolated from activated sludge and the isolate possessed an average nitrate removal efficiency of 95.8% in 24 h, with the maximum nitrite accumulation of 25.6 mg/l. The bacterium could not conduct heterotrophic nitrification. The results of PCR indicated that the strain lacked the gene of amoA. The phylogenetic tree indicated a clear evolutionary divergence that Pseudomonas stutzeri C3 belonged to the group of strains that could not exhibit ammonia oxidation. PMID- 25115801 TI - B-Type natriuretic peptide suppression of neutrophil superoxide generation: mechanistic studies in normal subjects. AB - Many acute cardiovascular disease states are associated with neutrophil infiltration of myocardium and subsequent release of superoxide (O2 (-) ) and myeloperoxidase (MPO), which contribute to inflammatory reactions. B-Type natriuretic peptide (BNP) is known to exert anti-inflammatory and antifibrotic effects, but it is not known whether these may include interactions with neutrophils. In neutrophils isolated from 20 healthy subjects, we assessed the effect of BNP on the 'neutrophil burst' (O2 (-) production and MPO release) stimulated by phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl phenylalanine (fMLP), respectively. Effects of BNP on cGMP accumulation, and the effects of the cell-permeable cGMP analogue 8-(4-chlorophenylthio) guanosine-cGMP (8-p-CPT-cGMP) and protein kinase G (PKG) inhibition with KT5823 on the neutrophil-BNP interaction were also evaluated. B-Type natriuretic peptide suppressed O2 (-) release from neutrophils by 23 +/- 6% (P < 0.001) and 24 +/- 8% (P < 0.05) following PMA and fMLP stimulation, respectively. Although BNP did not significantly increase cGMP formation, 8-p-CPT-cGMP suppressed both PMA- and fMLP induced neutrophil O2 (-) release by 16% and 28%, respectively (P < 0.05). The PKG inhibitor KT5823 attenuated the effects of BNP on both fMLP- and PMA associated O2 (-) production. Neither BNP nor 8-p-CPT-cGMP significantly affected MPO release from neutrophils. Suppression of O2 (-) release from neutrophils by BNP may contribute to its anti-inflammatory and antifibrotic actions. PMID- 25115800 TI - Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats. AB - Iron accumulates progressively in the brain with age, and iron-induced oxidative stress has been considered as one of the initial causes for Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the role of hepcidin in peripheral organs and its expression in the brain, we hypothesized that this peptide has a role to reduce iron in the brain and hence has the potential to prevent or delay brain iron accumulation in iron-associated neurodegenerative disorders. Here, we investigated the effects of hepcidin expression adenovirus (ad-hepcidin) and hepcidin peptide on brain iron contents, iron transport across the brain-blood barrier, iron uptake and release, and also the expression of transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin 1 (Fpn1) in cultured microvascular endothelial cells and neurons. We demonstrated that hepcidin significantly reduced brain iron in iron-overloaded rats and suppressed transport of transferrin-bound iron (Tf-Fe) from the periphery into the brain. Also, the peptide significantly inhibited expression of TfR1, DMT1, and Fpn1 as well as reduced Tf-Fe and non-transferrin-bound iron uptake and iron release in cultured microvascular endothelial cells and neurons, while downregulation of hepcidin with hepcidin siRNA retrovirus generated opposite results. We concluded that, under iron-overload, hepcidin functions to reduce iron in the brain by downregulating iron transport proteins. Upregulation of brain hepcidin by ad hepcidin emerges as a new pharmacological treatment and prevention for iron associated neurodegenerative disorders. PMID- 25115803 TI - Unravelling the structure of electrocatalytically active Fe-N complexes in carbon for the oxygen reduction reaction. AB - Non-precious Fe/N co-modified carbon electrocatalysts have attracted great attention due to their high activity and stability in oxygen reduction reaction (ORR). Compared to iron-free N-doped carbon electrocatalysts, Fe/N-modified electrocatalysts show four-electron selectivity with better activity in acid electrolytes. This is believed relevant to the unique Fe-N complexes, however, the Fe-N structure remains unknown. We used o,m,p-phenylenediamine as nitrogen precursors to tailor the Fe-N structures in heterogeneous electrocatalysts which contain FeS and Fe3 C phases. The electrocatalysts have been operated for 5000 cycles with a small 39 mV shift in half-wave potential. By combining advanced electron microscopy and Mossbauer spectroscopy, we have identified the electrocatalytically active Fe-N6 complexes (FeN6, [Fe(III)(porphyrin)(pyridine)2]). We expect the understanding of the FeN6 structure will pave the way towards new advanced Fe-N based electrocatalysts. PMID- 25115804 TI - Floating gate memory-based monolayer MoS2 transistor with metal nanocrystals embedded in the gate dielectrics. AB - Charge trapping layers are formed from different metallic nanocrystals in MoS2 based nanocrystal floating gate memory cells in a process compatible with existing fabrication technologies. The memory cells with Au nanocrystals exhibit impressive performance with a large memory window of 10 V, a high program/erase ratio of approximately 10(5) and a long retention time of 10 years. PMID- 25115802 TI - Role of far infra-red therapy in dialysis arterio-venous fistula maturation and survival: systematic review and meta-analysis. AB - INTRODUCTION: A well-functioning arteriovenous fistula (AVF) is the best modality for vascular access in patients with end-stage renal disease (ESRD) requiring haemodialysis (HD). However, AVFs' main disadvantage is the high rate of maturation failure, with approximately one third (20%-50%) not maturing into useful access. This review examine the use of Far-Infra Red therapy in an attempt to enhance both primary (unassisted) and secondary (assisted) patency rates for AVF in dialysis and pre-dialysis patients. METHOD: We performed an online search for observational studies and randomised controlled trials (RCTs) that evaluated FIR in patients with AVF. Eligible studies compared FIR with control treatment and reported at least one outcome measure relating to access survival. Primary patency and secondary patency rates were the main outcomes of interest. RESULTS: Four RCTs (666 patients) were included. Unassisted patency assessed in 610 patients, and was significantly better among those who received FIR (228/311) compared to (185/299) controls (pooled risk ratio of 1.23 [1.12-1.35], p = 0.00001). In addition, the two studies which reported secondary patency rates showed significant difference in favour of FIR therapy--160/168 patients- compared to 140/163 controls (pooled risk ratio of 1.11 [1.04-1.19], p = 0.003). CONCLUSION: FIR therapy may positively influence the complex process of AVF maturation improving both primary and secondary patency rates. However blinded RCTs performed by investigators with no commercial ties to FIR therapy technologies are needed. PMID- 25115806 TI - Post-mating morphological changes in the spermatozoon and spermatophore wall of the crayfish Astacus leptodactylus: insight into a non-motile spermatozoon. AB - Morphology of the crayfish spermatozoon and of the spermatophore wall during three stages of final maturation including freshly ejaculated, post-mating, and after spermatozoa release was studied and compared. The crayfish spermatophore consists of a sperm mass enveloped by a three layered spermatophore wall. After mating, the thickness of the outer layer of the spermatophore is increased. The matrix in the middle layer of the spermatophore becomes reticulated, and granules inside this layer release their contents. Fibers in the inner layer degrade to small particles. The spermatozoon capsule swells and the space between the capsule and the spermatozoon appears. The area of the plasma membrane is increased by wrinkling of the surface and alteration from a single to a multilayered structure at the anterior part of the acrosome. The density of the subacrosome zone increases in the vicinity of the main body of the acrosome. With the onset of fertilization, the layers of the spermatophore are dissolved by female glair gland secretions. The spermatozoon extracellular capsule, plasma membrane, and membranous lamellae are eliminated, and bundles of filaments are released from anterior part of the acrosome. The subacrosome zone loses electron density and retracts. The electron-dense material of the innermost layer of the acrosome is discharged and, together with acrosome filaments, forms a filament/droplet structure at the anterior part of the spermatozoon. The most important change is observed in the subacrosome zone, which may play a key role in the fertilization. Also, morphological changes of the spermatozoon that occur after release from the capsule, especially formation of the filament/droplet structure, may contribute to the mechanism of egg-spermatozoon binding in the crayfish, representative of animals with non-motile spermatozoa. PMID- 25115805 TI - Depletion of regulatory T cells augments a vaccine-induced T effector cell response against the liver-stage of malaria but fails to increase memory. AB - Regulatory T cells (T(reg)) have been shown to restrict vaccine-induced T cell responses in different experimental models. In these studies CD4(+)CD25(+) T(reg) were depleted using monoclonal antibodies against CD25, which might also interfere with CD25 on non-regulatory T cell populations and would have no effect on Foxp3(+)CD25(-) T(reg). To obtain more insights in the specific function of T(reg) during vaccination we used mice that are transgenic for a bacterial artificial chromosome expressing a diphtheria toxin (DT) receptor-eGFP fusion protein under the control of the foxp3 gene locus (depletion of regulatory T cell mice; DEREG). As an experimental vaccine-carrier recombinant Bordetella adenylate cyclase toxoid fused with a MHC-class I-restricted epitope of the circumsporozoite protein (ACT-CSP) of Plasmodium berghei (Pb) was used. ACT-CSP was shown by us previously to introduce the CD8+ epitope of Pb-CSP into the MHC class I presentation pathway of professional antigen-presenting cells (APC). Using this system we demonstrate here that the number of CSP-specific T cells increases when T(reg) are depleted during prime but also during boost immunization. Importantly, despite this increase of T effector cells no difference in the number of antigen-specific memory cells was observed. PMID- 25115807 TI - Effects of different levels of dietary selenium on the proliferation of spermatogonial stem cells and antioxidant status in testis of roosters. AB - The objective of this study was to investigate the different levels of dietary Se (from sodium selenite) on the proliferation of SSCs (spermatogonial stem cells) in testis of roosters. Also, the antioxidant status and Se content in blood plasma and testis were evaluated. A total of eighty 12-week-old Hy-Line Variety white roosters at an averaged body weight of 1.38 +/- 0.2 kg were selected and randomly divided into four experimental groups. They were fed with the basal diet (0.044 mgSe/kg DM) supplemented with 0 (control), 0.5, 1.0 or 2.0 mgSe/kg DM (from sodium selenite). After the feeding experiment, blood and testis samples were collected for analysis of the antioxidant status and Se concentration. The testis samples were also used to examine the Thy-1 and beta1-integrin mRNA expression by RT-PCR and detect the population of SSCs by immunofluorescence analysis. The results show that Se concentration in blood and testis of the animals was progressively increased with the increasing Se level in diet. The highest GSH-Px (glutathione peroxidase) activity and lowest MDA content in blood and testis was obtained in the treatment of 0.5mg/kg. RT-PCR analysis showed that mRNA expression of SSCs markers were significantly lower in the control and 1.0mg/kg groups when compared with that in the treatment of 0.5mg/kg. A similar trend was observed in the population of SSCs analyzed by immunofluorescence assay. These data suggest that dietary Se can influence the population of SSCs of roosters during spermatogenesis and that oxidative stress can modulate SSCs behavior through regulating some key factors during spermatogenesis. PMID- 25115808 TI - Outcome prediction by the transcript level of BCR-ABL at 3 months in patients with chronic myeloid leukemia treated with imatinib--a single institution historical experience. AB - The BCR-ABL transcript level (<= 10%) at 3 months after tyrosine kinase inhibitors can predict long term outcome in the patients with chronic myeloid leukemia in chronic phase (CML-CP). However, the significance of transcript level was still not determined in different risk groups of patients. A total of 299 patients with CML-CP were enrolled and stratified according to prior interferon alpha (IFN) treatment, age, and interval time between diagnosis and imatinib treatment to investigate the prediction value of BCR-ABL transcript level for overall survival (OS), event-free survival (EFS), progression-free survival (PFS). Univariate and multivariate analysis proved that BCR-ABL transcript level at 3 months were associated with the treatment outcome. However, in the patients with prior IFN treatment, younger age, and longer interval between diagnosis and IM treatment, the predictive value of transcript value remain obscure in terms of EFS, PFS and OS, respectively, as well as cumulative incidence of PCyR, CCR, MMR and CMR. In conclusion, the transcript level of BCR-ABL at 3 months could serve as a predictive parameter, but should be used with caution. PMID- 25115810 TI - Solid organ transplant recipients: clinical considerations in the application of exercise. AB - Over 100 000 solid organ transplants are performed worldwide each year and this has a significant impact on physical function and quality of life. However, the capacity for exercise in solid-organ recipients is reduced. Regular physical activity improves most of the indices of fitness in these patients but, with few exceptions, they do not reach the values seen in healthy controls. The reason for the 40-60% reduction in maximal exercise capacity is not clear; the disease process, need for life long immunosuppression and sedentary lifestyle all contribute. The interaction between exercise and immunosuppressing medication merits research as does the specifics of the exercise prescription for these patients. This paper reviews important features of this rapidly expanding group of patients and suggests clinical considerations in the application of exercise in this population. PMID- 25115811 TI - Self-assembly of three-dimensional open structures using patchy colloidal particles. AB - Open structures can display a number of unusual properties, including a negative Poisson's ratio, negative thermal expansion, and holographic elasticity, and have many interesting applications in engineering. However, it is a grand challenge to self-assemble open structures at the colloidal scale, where short-range interactions and low coordination number can leave them mechanically unstable. In this paper we discuss the self-assembly of three-dimensional open structures using triblock Janus particles, which have two large attractive patches that can form multiple bonds, separated by a band with purely hard-sphere repulsion. Such surface patterning leads to open structures that are stabilized by orientational entropy (in an order-by-disorder effect) and selected over close-packed structures by vibrational entropy. For different patch sizes the particles can form into either tetrahedral or octahedral structural motifs which then compose open lattices, including the pyrochlore, the hexagonal tetrastack and the perovskite lattices. Using an analytic theory, we examine the phase diagrams of these possible open and close-packed structures for triblock Janus particles and characterize the mechanical properties of these structures. Our theory leads to rational designs of particles for the self-assembly of three-dimensional colloidal structures that are possible using current experimental techniques. PMID- 25115809 TI - Recollection and familiarity in aging individuals with mild cognitive impairment and Alzheimer's disease: a literature review. AB - Memory impairment is a central cognitive symptom in mild cognitive impairment (MCI) and Alzheimer Disease (AD). Recognition tasks are often used to characterize and define the nature of memory deficits. Dual-process theories posit that familiarity and recollection are independently involved in the recognition of previously encountered material and both contribute to successful recognition. Recent evidence indicates that there is a double dissociation in the neuronal substrates of those two processes. More precisely, it has been suggested that perirhinal and entorhinal areas are selectively involved in familiarity based recognition, while the hippocampus is associated with recollection. Interestingly, these regions are among the first to be targeted by neurofibrillary tangles, one of AD's neuropathological hallmarks. Impairment in recognition performance can occur in the very early stages of AD, such as MCI. To define the nature of recognition impairment in these clinical populations, we reviewed the current literature on familiarity and recollection performance in individuals with MCI and AD. Together with clinical features, methodological factors are taken into consideration in the interpretation of findings. PMID- 25115812 TI - SdrC induces staphylococcal biofilm formation through a homophilic interaction. AB - The molecular pathogenesis of many Staphylococcus aureus infections involves growth of bacteria as biofilm. In addition to polysaccharide intercellular adhesin (PIA) and extracellular DNA, surface proteins appear to mediate the transition of bacteria from planktonic growth to sessile lifestyle as well as biofilm growth, and can enable these processes even in the absence of PIA expression. However, the molecular mechanisms by which surface proteins contribute to biofilm formation are incompletely understood. Here we demonstrate that self-association of the serine-aspartate repeat protein SdrC promotes both bacterial adherence to surfaces and biofilm formation. However, this homophilic interaction is not required for the attachment of bacteria to abiotic surfaces. We identified the subdomain that mediates SdrC dimerization and subsequent cell cell interactions. In addition, we determined that two adjacently located amino acid sequences within this subdomain are required for the SdrC homophilic interaction. Comparative amino acid sequence analysis indicated that these binding sites are conserved. In summary, our study identifies SdrC as a novel molecular determinant in staphylococcal biofilm formation and describes the mechanism responsible for intercellular interactions. Furthermore, these findings contribute to a growing body of evidence suggesting that homophilic interactions between surface proteins present on neighbouring bacteria induce biofilm growth. PMID- 25115814 TI - Oligodendroglial response in the spinal cord in TDP-43 proteinopathy with motor neuron involvement. AB - BACKGROUND: TDP-43 proteinopathies represent a spectrum of neurodegenerative disorders. Variable clinical presentations including frontotemporal dementia, amyotrophic lateral sclerosis (ALS) and mixed forms are associated with the spatial heterogeneity of the TDP-43 pathology. Recent studies have emphasized the role of oligodendrocytes in the pathogenesis of ALS. OBJECTIVE: To evaluate whether TDP-43 proteinopathies are associated with an oligodendroglial response. METHODS: We performed a study on 7 controls and 10 diseased patients with spinal cord involvement. Using the oligodendroglia-specific antibody TPPP/p25, we assessed oligodendrocyte density in the lateral corticospinal tracts (LCSs) along with the presence of perineuronal oligodendrocytes (PNOGs) in the anterior horns. We performed a densitometry of myelin basic protein (MBP) immunoreactivity. The numbers of TDP-43 and p62 immunoreactive inclusions were counted in both the LCSs and the anterior horns. RESULTS: Double immunolabeling confirmed that oligodendrocytes harbor TDP-43 inclusions. In the LCSs, MBP density, but not the number of oligodendrocytes, was decreased in the diseased group. However, oligodendrocyte counts in the LCS correlated positively, and the density of MBP inversely, with the number of neuronal inclusions in the anterior horn, suggestive of a compensatory response of oligodendrocytes. The number of neurons with PNOGs correlated with the amount of inclusions. CONCLUSION: Our study further emphasizes the importance of oligodendroglia in the pathogenesis of TDP 43 proteinopathies with spinal cord involvement. PMID- 25115813 TI - The need for improved identification and accurate classification of stages 3-5 Chronic Kidney Disease in primary care: retrospective cohort study. AB - BACKGROUND: Around ten percent of the population have been reported as having Chronic Kidney Disease (CKD), which is associated with increased cardiovascular mortality. Few previous studies have ascertained the chronicity of CKD. In the UK, a payment for performance (P4P) initiative incentivizes CKD (stages 3-5) recognition and management in primary care, but the impact of this has not been assessed. METHODS AND FINDINGS: Using data from 426 primary care practices (population 2,707,130), the age standardised prevalence of stages 3-5 CKD was identified using two consecutive estimated Glomerular Filtration Rates (eGFRs) seven days apart. Additionally the accuracy of practice CKD registers and the relationship between accurate identification of CKD and the achievement of P4P indicators was determined. Between 2005 and 2009, the prevalence of stages 3-5 CKD increased from 0.3% to 3.9%. In 2009, 30,440 patients (1.1% unadjusted) fulfilled biochemical criteria for CKD but were not on a practice CKD register (uncoded CKD) and 60,705 patients (2.2% unadjusted) were included on a practice CKD register but did not fulfil biochemical criteria (miscoded CKD). For patients with confirmed CKD, inclusion in a practice register was associated with increasing age, male sex, diabetes, hypertension, cardiovascular disease and increasing CKD stage (p<0.0001). Uncoded CKD patients compared to miscoded patients were less likely to achieve performance indicators for blood pressure (OR 0.84, 95% CI 0.82-0.86 p<0.001) or recorded albumin-creatinine ratio (OR 0.73, 0.70-0.76, p<0.001). CONCLUSIONS: The prevalence of stages 3-5 CKD, using two laboratory reported eGFRs, was lower than estimates from previous studies. Clinically significant discrepancies were identified between biochemically defined CKD and appearance on practice registers, with misclassification associated with sub-optimal care for some people with CKD. PMID- 25115816 TI - Biomechanical considerations of foot-ground contact in T'ai Chi Chuan. AB - Although numerous studies have linked t'ai chi chuan (TCC) practice with benefits for balance, reduction in the number of falls, and in the fear of falling, most of them did not address the causes of these benefits in depth. Some studies, however, sought to determine the causes from the biomechanical point of view. This article aims to thoroughly describe and critically review recent papers on foot-ground contact in TCC practice, one of the parameters involved in balance biomechanics in TCC performance. No previous review on this subject has been found. Nine electronic databases were searched for publications between 1996 and 2013. Studies were excluded if they were not published in English or were abstracts, posters, or summaries from conferences. From a total of 195 articles identified, 4 randomized controlled trials and 3 non-randomized controlled trials were eligible for the analysis. The number of studies that assessed foot-ground contact in TCC and effects on normal gait, postural control improvement, and fall prevention is still quite small. These studies were based on intervention protocols and used populations that were too heterogeneous to allow reliable comparisons. According to the studies analyzed, TCC practice clearly improved parameters associated with foot-ground contact. Nevertheless, the manner in which these benefits are transferred to daily displacement habits still remains unclear. PMID- 25115818 TI - Taming molecular collisions using electric and magnetic fields. AB - The motion of molecules that possess a permanent electric or magnetic dipole moment can be manipulated using electric or magnetic fields. Various devices have been developed over the last few decades to deflect or focus molecules, to orient them in space, and to decelerate or accelerate them. These precisely controlled molecules are ideal starting points for scattering experiments that reveal the quantum mechanical nature of molecular interactions. In this Tutorial Review, we present an overview of the various manipulation tools, discuss how they can be used to advantage in molecular beam scattering experiments, and review recent progress in this field. We describe a selection of benchmark experiments that illustrate the unique possibilities that are available nowadays to study molecular collisions under controlled conditions. PMID- 25115815 TI - Identification and characterization of Dicer1e, a Dicer1 protein variant, in oral cancer cells. AB - BACKGROUND: The human dicer1 gene has been predicted to produce several mRNA variants that encode truncated Dicer1 proteins of varying lengths. One of these Dicer1 variants, Dicer1e, was recently found to be differentially expressed in breast cancer cells. Because the expression and function of the Dicer1e protein variant has not been well characterized and the underlying molecular mechanisms for the development of oral squamous cell carcinomas (OSCCs) are poorly understood, the present study sought to characterize the biological role of Dicer1e and determine its relationship, if any, to OSCC pathogenesis. METHODS: Western blot analyses were used to examine Dicer1e expression levels in a panel of oral cancer cells/tissues and during epithelial-mesenchymal transition (EMT), followed by 5'/3'-RACE analyses to obtain the full-length Dicer1e transcript. Biochemical fractionation and indirect immunofluorescent studies were performed to determine the cellular localization of Dicer1e and the effects of Dicer1e silencing on cancer cell proliferation, clonogenicity, and drug sensitivity were also assessed. RESULTS: Dicer1e protein levels were found to be overexpressed in OSCC cell lines of epithelial phenotype and in OSCC tissues with its levels downregulated during EMT. Moreover, the Dicer1e protein was observed to predominantly localize in the nucleus. 5'/3'-RACE analyses confirmed the presence of the Dicer1e transcript and silencing of Dicer1e impaired both cancer cell proliferation and clonogenicity by inducing either apoptosis and/or G2/M cell cycle arrest. Lastly, Dicer1e knockdown enhanced the chemosensitivity of oral cancer cells to cisplatin. CONCLUSION: The expression levels of Dicer1e influence the pathogenesis of oral cancer cells and alter their response to chemosensitivity, thus supporting the importance of Dicer1e as a therapeutic target for OSCCs. PMID- 25115817 TI - Corner store purchases made by adults, adolescents and children: items, nutritional characteristics and amount spent. AB - OBJECTIVE: Corner stores, also known as bodegas, are prevalent in low-income urban areas and primarily stock high-energy foods and beverages. Little is known about individual-level purchases in these locations. The purpose of the present study was to assess corner store purchases (items, nutritional characteristics and amount spent) made by children, adolescents and adults in a low-income urban environment. DESIGN: Evaluation staff used 9238 intercept surveys to directly examine food and beverage purchases. SETTING: Intercepts were collected at 192 corner stores in Philadelphia, PA, USA. SUBJECTS: Participants were adult, adolescent and child corner store shoppers. RESULTS: Among the 9238 intercept surveys, there were 20 244 items. On average, at each corner store visit, consumers purchased 2.2 (sd 2.1) items (1.3 (sd 2.0) foods and 0.9 (sd 0.9) beverages) that cost $US 2.74 (sd $US 3.52) and contained 2786.5 (sd 4454.2) kJ (666.0 (sd 1064.6) kcal). Whether the data were examined as a percentage of total items purchased or as a percentage of intercepts, the most common corner store purchases were beverages, chips, prepared food items, pastries and candy. Beverage purchases occurred during 65.9% of intercepts and accounted for 39.2% of all items. Regular soda was the most popular beverage purchase. Corner store purchases averaged 66.2 g of sugar, 921.1 mg of sodium and 2.5 g of fibre per intercept. Compared with children and adolescents, adults spent the most money and purchased the most energy. CONCLUSIONS: Urban corner store shoppers spent almost $US 3.00 for over 2700 kJ (650 kcal) per store visit. Obesity prevention efforts may benefit from including interventions aimed at changing corner store food environments in low-income, urban areas. PMID- 25115819 TI - The effect of tooth loss on gait stability of community-dwelling older adults. AB - OBJECTIVE: To investigate the effects of tooth loss on gait stability in a healthy elderly population. METHODS: A case-control study was conducted among healthy and prosthetically well-restored seniors over the age of 65 years. The test group comprised 24 edentulous participants who were restored with complete dentures in the upper jaw and an overdenture fixed on two implants in the lower jaw. The control group comprised 25 dentate participants who either still had their natural teeth or were restored with conventional fixed partial dentures. Gait stability was evaluated by measuring the parameters 'gait velocity' and 'cycle-time variability' during self-selected normal walking speed and under dual task performance conditions. Measurements were conducted using the GAITRite((r)) electronic walkway system. RESULTS: Dentated and fixed restored participants (the control group) had a significantly higher gait velocity compared with denture wearers (the test group) under both normal walking (p = 0.03) and dual-task performance conditions (p = 0.01). In each test condition, among edentulous participants, gait velocity did not significantly differ according to whether the participant wore their dentures. CONCLUSION: The present results suggest that tooth loss in healthy seniors is associated with lower gait velocity and therefore may have a negative impact on gait stability. PMID- 25115820 TI - Epilepsy surgery in children: why, when and how? AB - Epilepsy surgery is safe and effective treatment in children who fail to respond to antiepileptic medications. After failure of two appropriate antiepileptic medications, chances that the child will become seizure free with more or different medications is <5%, and she should be diagnosed with "refractory epilepsy". A consideration for surgical candidacy should be given to all children who fulfill the definition of refractory epilepsy. In appropriately selected children, epilepsy surgery offers a high chance of seizure freedom without incurring any new post-operative neurological deficits. No age is bar to epilepsy surgery. Even infants can safely have epilepsy surgery if they are surgical candidates. For most children, who are surgical candidates, a good history and physical examination, video EEG evaluation, and a high quality brain MRI are sufficient to make surgical decision. These tools are increasingly available all over the world. Better education of families, Pediatricians, Pediatric Neurologists and community care-givers is necessary to salvage children early from mortality and morbidity of untreated, sometimes life long, epilepsy. PMID- 25115824 TI - Direct synthesis of chromium perovskite oxyhydride with a high magnetic transition temperature. AB - We report a novel oxyhydride SrCrO2H directly synthesized by a high-pressure high temperature method. Powder neutron and synchrotron X-ray diffraction revealed that this compound adopts the ideal cubic perovskite structure (Pm3m) with O(2 )/H(-) disorder. Surprisingly, despite the non-bonding nature between Cr 3d t(2g) orbitals and the H 1s orbital, it exhibits G-type spin ordering at T(N)~380 K, which is higher than that of RCrO3 (R=rare earth) and any chromium oxides. The enhanced T(N) in SrCrO2H with four Cr-O-Cr bonds in comparison with RCr(3+)O3 with six Cr-O-Cr bonds is reasonably explained by the tolerance factor. The present result offers an effective strategy to tune octahedral tilting in perovskites and to improve physical and chemical properties through mixed anion chemistry. PMID- 25115823 TI - Role of peripheral purinoceptors in the development of bee venom-induced nociception: a behavioural and electrophysiological study in rats. AB - Colocalization of purinergic P2X and P2Y receptors in dorsal root ganglion sensory neurons implies that these receptors play an integrative role in the nociceptive transmission process under inflammatory conditions. In the present study, behavioural and in vivo electrophysiological methods were used to examine the peripheral role of P2 receptors in the persistent nociceptive responses induced by subcutaneous bee venom injection (2 mg/mL) in. Sprague-Dawley rats Local pretreatment with the wide-spectrum P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 1 mmol/L, 50 MUL) 10 min prior to s.c. bee venom injection significantly suppressed the duration of spontaneous nociceptive lifting/licking behaviour, inhibited mechanical hyperalgesia and decreased the firing of spinal dorsal horn wide dynamic range neurons in response to bee venom, without affecting primary thermal and mirror image hyperalgesia. The localized antinociceptive action of PPADS was not due to a systemic effect, because application of the same dose of PPADS to the contralateral side was not effective. The results suggest that activation of peripheral P2 receptors is involved in the induction of nociceptive responses, mechanical hyperalgesia and the excitation of sensory spinal neurons. PMID- 25115825 TI - Facet-dependent surface plasmon resonance properties of Au-Cu2 o core-shell nanocubes, octahedra, and rhombic dodecahedra. AB - Au-Cu2 O core-shell nanocubes, octahedra, and rhombic dodecahedra display facet dependent optical properties. Furthermore, different-sized Au-Cu2 O octahedra with 58, 65, 68, and 73 nm octahedral gold cores clearly show a transition from the shell thickness-independent gold surface plasmon resonance band for octahedra with smaller gold cores to progressive red-shifts of the band with increasing shell thickness in octahedra with larger gold cores. PMID- 25115821 TI - Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea. AB - While autonomic outflow is an important co-factor of nausea physiology, central control of this outflow is poorly understood. We evaluated sympathetic (skin conductance level) and cardiovagal (high-frequency heart rate variability) modulation, collected synchronously with functional MRI (fMRI) data during nauseogenic visual stimulation aimed to induce vection in susceptible individuals. Autonomic data guided analysis of neuroimaging data, using a stimulus-based (analysis windows set by visual stimulation protocol) and percept based (windows set by subjects' ratings) approach. Increased sympathetic and decreased parasympathetic modulation was associated with robust and anti correlated brain activity in response to nausea. Specifically, greater autonomic response was associated with reduced fMRI signal in brain regions such as the insula, suggesting an inhibitory relationship with premotor brainstem nuclei. Interestingly, some sympathetic/parasympathetic specificity was noted. Activity in default mode network and visual motion areas was anti-correlated with parasympathetic outflow at peak nausea. In contrast, lateral prefrontal cortical activity was anti-correlated with sympathetic outflow during recovery, soon after cessation of nauseogenic stimulation. These results suggest divergent central autonomic control for sympathetic and parasympathetic response to nausea. Autonomic outflow and the central autonomic network underlying ANS response to nausea may be an important determinant of overall nausea intensity and, ultimately, a potential therapeutic target. PMID- 25115826 TI - Association of bone mineral density with postural stability and the fear of falling in Spanish postmenopausal women. AB - OBJECTIVE: The purpose of our study was to investigate the relationship between bone mineral density (BMD) and postural stability and the fear of falling in a 50 to 65-year-old postmenopausal population. STUDY DESIGN: A cross-sectional, observational study was conducted on 118 postmenopausal women. According to their BMD values, participants were divided into two groups: BMD>-2.0SD (n=95) and <= 2.0SD (n=23). MAIN OUTCOME MEASURES: Postural stability, assessed with a resistive multi-sensor platform, fear of falling (FoF) and the history of falls in the last 12 months were investigated. RESULTS: Women with BMD<=-2.0SD reported a significantly increased FoF when compared to women with BMD>-2.0SD (P=0.024, eta(2)=0.045, 1-beta=0.624). In the postural stability analysis, the group with BMD<=-2.0SD showed, under the eyes-open condition, statistically significantly higher values for the velocity (VEO) (P=0.040, eta(2)=0.037, 1-beta=0.539) and the anteroposterior mean displacement of the center of pressure (YEO; P=0.017, eta(2)=0.049, 1-beta=0.669). No significant differences between groups were observed in the history of falls or in the rest of the stabilometric analyses. CONCLUSIONS: In Spanish postmenopausal women under 65 years, a BMD<=-2.0SD is significantly associated with postural instability (elevated VEO and XEO) and an increased FoF, which are two highly influential factors in the risk of falling. PMID- 25115828 TI - Predicting drug substances autoxidation. AB - PURPOSE: Chemical degradation and stability in formulation is a recurrent issue in pharmaceutical development of drugs. The objective of the present study was to develop an in silico risk assessment of active pharmaceutical ingredients (APIs) stability with respect to autoxidation. METHODS: The chemical degradation by autoxidation of a diverse series of APIs has been investigated with molecular modelling tools. A set of 45 organic compounds was used to test and validate the various computational settings. Aiming to devise a methodology that could reliably perform a risk assessment for potential sensibility to autoxidation, different types of APIs, known for their autoxidation history were inspected. To define the level of approximation needed, various density functional theory (DFT) functionals and settings were employed and their accuracy and speed were compared. RESULTS: The Local Density Approximation (LDA) gave the fastest results but with a substantial deviation (systematic over-estimation) to known experimental values. The Perdew-Burke-Ernzerhof (PBE) settings appeared to be a good compromise between speed and accuracy. CONCLUSIONS: The present methodology can now be confidently deployed in pharmaceutical development for systematic risk assessment of drug stability. PMID- 25115827 TI - In vitro and in vivo biological evaluation of O-carboxymethyl chitosan encapsulated metformin nanoparticles for pancreatic cancer therapy. AB - PURPOSE: In vitro anticancer effect and in vivo biodistribution and biocompatibility of metformin encapsulated O-Carboxymethyl chitosan nanoparticles were evaluated for its application as pancreatic cancer therapy. METHODS: In vitro studies such as cell migration assay, clonogenic assay, cell cycle analysis and qRT-PCR analysis were done in pancreatic cancer cells (MiaPaCa-2) treated with O-CMC-metformin NPs for evaluating its anticancer potential. In vivo biodistribution studies were carried out by NIR imaging of O-CMC-metformin NPs after tagging it with ICG. In vivo biocompatibility of the NPs was assessed by histopathology analysis of organs from mice administered with the NPs. RESULTS: In vitro cell migration assay showed marginal effect of NPs on migration property of pancreatic cancer cells (MiaPaCa-2). In vitro clonogenic assay established that the O-CMC-metformin NPs reduced colony formation ability of the cancer cells. While cell cycle analysis showed that the O-CMC-metformin NPs had only minor effect on progression of cell cycle in the cancer cells. qRT-PCR analysis exhibited reduced mRNA expression of p21, vanin 1 and MMP9 in pancreatic cancer cells treated with the nanoparticles. In vivo NIR imaging study showed normal biodistribution pattern of the intravenously injected O-CMC-metformin NPs suggesting normal clearance rate of nanoparticles and no adverse toxicity to the organs. CONCLUSIONS: The biocompatible O-CMC-metformin NPs with anticancer potential and capability for normal biodistribution can be beneficial for the treatment of pancreatic cancer. PMID- 25115829 TI - Bisoprolol and bisoprolol-valsartan compatibility studied by differential scanning calorimetry, nuclear magnetic resonance and X-ray powder diffractometry. AB - PURPOSE: The objective of this study was to evaluate the thermal behavior of crystalline and amorphous bisoprolol fumarate and its compatibility with amorphous valsartan. This pharmacologically relevant drug combination is a potential candidate for fixed-dose combination formulation. METHODS: DSC and TMDSC were used to examine thermal behavior of bisoprolol fumarate. SSNMR and XRPD were applied to probe the solid state forms. The thermal behavior of physical mixtures with different concentrations of bisoprolol and valsartan were examined by DSC and TMDSC, and the observed interactions were investigated by XRPD, solution- and solid-state NMR. RESULTS: The phase transitions from thermal methods and solid-state NMR spectra of crystalline and amorphous bisoprolol fumarate are reported. Strong interactions between bisoprolol fumarate and valsartan were observed above 60 C, resulting in the formation of a new amorphous material. Solution- and solid-state NMR provided insight into the molecular nature of the incompatibility. CONCLUSIONS: A combined analysis of thermal methods, solution- and solid-state NMR and XRPD experiments allowed the investigation of the conformational and dynamic properties of bisoprolol fumarate. Since bisoprolol fumarate and valsartan react to form a new amorphous product, formulation of a fixed-dose combination would require separate reservoirs for bisoprolol and valsartan to prevent interactions. Similar problems might be expected with other excipients or APIs containing carboxylic groups. PMID- 25115830 TI - Human exposure to early morning Anopheles funestus biting behavior and personal protection provided by long-lasting insecticidal nets. AB - A shift towards early morning biting behavior of the major malaria vector Anopheles funestus have been observed in two villages in south Benin following distribution of long-lasting insecticidal nets (LLINs), but the impact of these changes on the personal protection efficacy of LLINs was not evaluated. Data from human and An. funestus behavioral surveys were used to measure the human exposure to An. funestus bites through previously described mathematical models. We estimated the personal protection efficacy provided by LLINs and the proportions of exposure to bite occurring indoors and/or in the early morning. Average personal protection provided by using of LLIN was high (>=80% of the total exposure to bite), but for LLIN users, a large part of remaining exposure occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoue) and/or in the early morning (38.5% in Tokoli-V and 69.4% in Lokohoue). This study highlights the crucial role of LLIN use and the possible need to develop new vector control strategies targeting malaria vectors with outdoor and early morning biting behavior. This multidisciplinary approach that supplements entomology with social science and mathematical modeling illustrates just how important it is to assess where and when humans are actually exposed to malaria vectors before vector control program managers, policy-makers and funders conclude what entomological observations imply. PMID- 25115832 TI - Investigation into the effect of hepatitis B virus on apoliprotein A1 expression and its mechanism. AB - BACKGROUND: Hepatitis B virus (HBV) infection poses a serious threat to human health, with China being one of the highly affected countries. However, the pathogenesis of chronic hepatitis B (CHB) is still unclear. Apolipoprotein A1 (ApoA1) which represents the major protein component of high-density lipoprotein is normally secreted by hepatocytes. When hepatocytes are infected with HBV may lead to the disruption of ApoA1 secretion. In this study, we investigated the effect of HBV on ApoA1 expression and preliminarily explored its molecular mechanism of regulation for revealing the pathogenesis of CHB. METHODS: The expression of mRNA and protein of ApoA1 in Human HepG2 hepatoblastoma cells and subline HepG2.2.15 cells were performed by reverse transcription-polymerase chain reaction (RT-PCR) and Western-blot. The serum ApoA1, by the immune turbidimetric test, and high-density lipoprotein cholesterol (HDL-C) in CHB patients and healthy controls, based on the enzymatic method, were measured with autobiochemical analyzer. The statistical difference was analyzed by SPSS 13.0. HBV infectious clone, pHBV1.3, and ApoA1 gene promoter were co-transfected into HepG2, and the luciferase activity was determined. The changes of ApoA1 mRNA and protein expression were detected by RT-PCR and Western-blot method, after HepG2 cells were transfected with pHBV1.3. RESULTS: The expression of ApoA1 mRNA and protein in HepG2.2.15 were lower than those in HepG2, and when compared with healthy controls, serum levels of ApoA1 and HDL-C in CHB patients were lower (P < 0.05). pHBV1.3 in HepG2 cells restrained the activity of ApoA1 promoter, mRNA and protein expression. CONCLUSIONS: HBV could inhibit the expression of ApoA1 in vitro and in vivo. PMID- 25115831 TI - Unique aspects of impulsive traits in substance use and overeating: specific contributions of common assessments of impulsivity. AB - Abstract Background: Impulsivity is a complex trait often studied in substance abuse and overeating disorders, but the exact nature of impulsivity traits and their contribution to these disorders are still debated. Thus, understanding how to measure impulsivity is essential for comprehending addictive behaviors. OBJECTIVES: Identify unique impulsivity traits specific to substance use and overeating. METHODS: Impulsive Sensation Seeking (ImpSS) and Barratt's Impulsivity scales (BIS) Scales were analyzed with a non-parametric factor analytic technique (discriminant correspondence analysis) to identify group specific traits on 297 individuals from five groups: Marijuana (n = 88), Nicotine (n = 82), Overeaters (n = 27), Marijuauna + Nicotine (n = 63), and CONTROLs (n = 37). RESULTS: A significant overall factor structure revealed three components of impulsivity that explained respectively 50.19% (pperm < 0.0005), 24.18% (pperm < 0.0005), and 15.98% (pperm < 0.0005) of the variance. All groups were significantly different from one another. When analyzed together, the BIS and ImpSS produce a multi-factorial structure that identified the impulsivity traits specific to these groups. The group specific traits are (1) CONTROL: low impulse, avoids thrill-seeking behaviors; (2) Marijuana: seeks mild sensation, is focused and attentive; (3) Marijuana + Nicotine: pursues thrill-seeking, lacks focus and attention; (4) Nicotine: lacks focus and planning; (5) Overeating: lacks focus, but plans (short and long term). CONCLUSIONS: Our results reveal impulsivity traits specific to each group. This may provide better criteria to define spectrums and trajectories - instead of categories - of symptoms for substance use and eating disorders. Defining symptomatic spectrums could be an important step forward in diagnostic strategies. PMID- 25115833 TI - Pirfenidone in idiopathic pulmonary fibrosis: real-life experience from a German tertiary referral center for interstitial lung diseases. AB - BACKGROUND: Pirfenidone is a novel antifibrotic drug for the treatment of mild-to moderate idiopathic pulmonary fibrosis (IPF). However, adverse events may offset treatment benefits and compliance. OBJECTIVES: To assess recent course of disease, adverse events and compliance in patients who started pirfenidone. METHODS: In an observational cohort study, 63 patients with mild-to-moderate IPF who started pirfenidone between May 2011 and June 2013 were reviewed. Pulmonary function, adverse events and treatment compliance were recorded at each clinic visit. Disease progression was defined as a reduction of vital capacity >=10% and/or diffusion capacity (DLCO) >=15%. RESULTS: Follow-up time on pirfenidone treatment was 11 (+/-7) months. Sixty-six percent of the patients continued with pirfenidone monotherapy and 34% of the patients received pirfenidone combined with corticosteroids (CCS) and/or N-acetylcysteine (NAC). There was a nonsignificant reduction in mean decline of percent predicted forced vital capacity after treatment start (0.7 +/- 10.9%) compared to the pretreatment period (6.6 +/- 6.7%, p = 0.098). Sixty-two percent of the patients had stable disease on pirfenidone treatment. Adverse events affected 85% of the patients, leading to discontinuation of pirfenidone in 20%. Adverse events and treatment discontinuation were seen more frequently in patients with concomitant CCS and/or NAC treatment. CONCLUSIONS: Adverse events affect the majority of patients treated with pirfenidone, but are mostly manageable with supportive measures. In this heterogeneous patient group, a nonsignificant effect of pirfenidone treatment on pulmonary function was seen, underlining the need for more data on patient selection criteria and efficacy of pirfenidone, particularly in patients with coexistent emphysema and concomitant NAC/CCS treatment. PMID- 25115834 TI - Severe oral infection due to Lactobacillus rhamnosus during induction chemotherapy for acute myeloid leukemia. AB - We report a case of severe oral infection with a high fever due to Lactobacillus rhamnosus during induction chemotherapy for acute myeloid leukemia. The patient did not improve on treatment with meropenem, clindamycin, or vancomycin until neutrophil recovery. Since L. rhamnosus GG is used in dairy products, and the patient ingested dairy products daily before starting chemotherapy, we suspected an association between the ingestion of dairy products and the development of infection. Pulsed-field gel electrophoresis using two different restriction enzymes showed that the strain isolated from the patient was identical to the L. rhamnosus GG strain isolated from dairy products and ATCC #53103. This was confirmed by a PCR assay with species-specific L. rhamnosus GG primers. Since Lactobacillus infection, particularly L. rhamnosus infection, can be fatal in immunocompromised hosts, we should consider Lactobacillus as a causative organism when Gram-positive rods are detected during treatment with broad-spectrum antibiotics and vancomycin. The causal association between the ingestion of dairy products containing Lactobacillus and Lactobacillus infection in immunocompromised hosts warrants further study. PMID- 25115835 TI - One-pot enzymatic synthesis of merochlorin A and B. AB - The polycycles merochlorin A and B are complex halogenated meroterpenoid natural products with significant antibacterial activities and are produced by the marine bacterium Streptomyces sp. strain CNH-189. Heterologously produced enzymes and chemical synthesis are employed herein to fully reconstitute the merochlorin biosynthesis in vitro. The interplay of a dedicated type III polyketide synthase, a prenyl diphosphate synthase, and an aromatic prenyltransferase allow formation of a highly unusual aromatic polyketide-terpene hybrid intermediate which features an unprecedented branched sesquiterpene moiety from isosesquilavandulyl diphosphate. As supported by in vivo experiments, this precursor is furthermore chlorinated and cyclized to merochlorin A and isomeric merochlorin B by a single vanadium-dependent haloperoxidase, thus completing the remarkably efficient pathway. PMID- 25115837 TI - Automated formation of lipid membrane microarrays for ionic single-molecule sensing with protein nanopores. AB - Efficient use of membrane protein nanopores in ionic single-molecule sensing requires technology for the reliable formation of suspended molecular membranes densely arrayed in formats that allow high-resolution electrical recording. Here, automated formation of bimolecular lipid layers is shown using a simple process where a poly(tetrafluoroethylene)-coated magnetic bar is remotely actuated to perform a turning motion, thereby spreading phospholipid in organic solvent on a nonpolar surface containing a <1 mm(2) 4 * 4 array of apertures with embedded microelectrodes (microelectrode cavity array). Parallel and high-resolution single-molecule detection by single nanopores is demonstrated on the resulting bilayer arrays, which are shown to form by a classical but very rapid self assembly process. The technique provides a robust and scalable solution for the problem of reliable, automated formation of multiple independent lipid bilayers in a dense microarray format, while preserving the favorable electrical properties of the microelectrode cavity array. PMID- 25115836 TI - A prospective study of gynecological cancer risk in relation to adiposity factors: cumulative incidence and association with plasma adipokine levels. AB - BACKGROUND: Associations of obesity and obesity-related metabolic factors (adiposity factors) with uterine corpus cancer (UCC) and ovarian cancer (OVC) risk have been described. Still, a cause-effect relationship and the underlying mediators remain unclear, particularly for low-incidence populations. We aimed to prospectively determine whether adiposity factors could predict the development of UCC and OVC in Taiwanese women. To explore the biological mediators linking adiposity factors to cancer risk, we examined the association of two adipokines, leptin and adiponectin, with the gynecological cancers. METHODS: Totally, 11,258 women, aged 30-65, were recruited into the Community-Based Cancer Screening Program (CBCSP) study during 1991-1993, and were followed for UCC and OVC cases until December 31, 2011. Cox proportional hazard models were used to estimate hazard ratios (HRs). Adiposity factors and risk covariates were assessed at recruitment. Newly-developed cancer cases were determined from data in the government's National Cancer Registry and Death Certification System. For adipokienes study, a nested case-control study was conducted within the cohort. Baseline plasma samples of 40 incident gynecological cancer cases and 240 age menopause-matched controls were assayed for adipokines levels. FINDINGS: There were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake (HR = 16.00, 95% = 4.83-53.00), high triglyceride levels (HR = 2.58, 95% = 1.28 5.17), and years of endogenous estrogen exposure per 5-year increment (HR = 1.91, 95% = 1.08-3.38) were associated with increased UCC risk. High body mass index (BMI >= 27 kg/m(2), HR = 2.90, 95% = 1.30-6.46) was associated with increased OVC risk. Analysis further showed an independent effect of adipokines on UCC and OVC risk after adjustment of the risk covariates. CONCLUSION: We provided evidence that alcohol intake, high triglyceride levels and long endogenous estrogen exposure increase UCC risk, whereas obesity positively predicts OVC risk. Circulating adipokines may mediate the link of adiposity factors to gynecological cancer risk. PMID- 25115838 TI - Modulation of platelet activation and thrombus formation using a pan-PI3K inhibitor S14161. AB - The phosphatidylinositol 3-kinase (PI3K) signaling pathway is critical in modulating platelet functions. In the present study, we evaluated the effect of S14161, a recently identified pan-class I PI3K inhibitor, on platelet activation and thrombus formation. Results showed that S14161 inhibited human platelet aggregation induced by collagen, thrombin, U46619, and ADP in a dose-dependent manner. Flow cytometric studies showed that S14161 inhibited convulxin- or thrombin-induced P-selectin expression and fibrinogen binding of single platelet. S14161 also inhibited platelet spreading on fibrinogen and clot retraction, processes mediated by outside-in signaling. Using a microfluidic chamber we demonstrated that S14161 decreased platelet adhesion on collagen-coated surface by about 80%. Western blot showed that S14161 inhibited phosphorylation of Akt at both Ser473 and Thr308 sites, and GSK3beta at Ser9 in response to collagen, thrombin, or U46619. Comparable studies showed that S14161 has a higher potential bioavailability than LY294002, a prototypical inhibitor of pan-class I PI3K. Finally, the effects of S14161 on thrombus formation in vivo were measured using a ferric chloride-induced carotid artery injury model in mice. The intraperitoneal injection of S14161 (2 mg/kg) to male C57BL/6 mice significantly extended the first occlusion time (5.05 +/- 0.99 min, n = 9) compared to the vehicle controls (3.72 +/- 0.95 min, n = 8) (P<0.05), but did not prolong the bleeding time (P>0.05). Taken together, our data showed that S14161 inhibits platelet activation and thrombus formation without significant bleeding tendency and toxicity, and considering its potential higher bioavailability, it may be developed as a novel therapeutic agent for the prevention of thrombotic disorders. PMID- 25115839 TI - Thrombophilic factor analysis in cirrhotic patients with portal vein thrombosis. AB - Liver cirrhosis, myeloproliferative disorders (MPDs) and prothrombotic mutations are aetiologic factors for portal vein thrombosis (PVT). The role and frequency of thrombophilic genetic risk factors in cirrhotic patients is not well established. In this case-control study, we investigated the frequency of Janus kinase 2 (JAK2) (JAK2 V617F), Factor V Leiden (FVL G1691A), and Prothrombin (G20210A) mutations in cirrhotic patients with PVT (LCi+/PVT+ group, n = 21) in comparison with two control collectives (cirrhotic patients without PVT, LCi+/PVT group, n = 43; PVT patients without liver cirrhosis, LCi-/PVT+ group, n = 29). In the LCi+/PVT+ group, JAK2 V617F was present in 2/21 patients (10 %; p = 0.104 compared to LCi+/PVT-; p = 0.092 compared to LCi-/PVT+), whereas 0/43 LCi+/PVT- patients (0 %; p < 0.001 compared to LCi-/PVT+) and 9/29 LCi-/PVT+ patients (31 %) harboured this mutation. The FVL G1691A mutation was identified in 1/21 patients (5 %) in the LCi+/PVT+ group, in 5/43 patients (12 %) in the LCi+/PVT- group, and in 2/29 patients (7 %) in the LCi-/PVT+ group. The Prothrombin G20210A mutation was present in 0/21 LCi+/PVT+ patients (0 %), in 1/43 LCi+/PVT- patients (2 %), and in 4/29 patients (14 %) in the LCi-/PVT+ group. This study provides evidence that a relevant proportion of cirrhotic patients with PVT harbours a JAK2 V617F mutation. PMID- 25115842 TI - Obesity, abdominal obesity and migraine: a cross-sectional analysis of ELSA Brasil baseline data. AB - BACKGROUND AND AIM: Most studies assessing the association between migraine and obesity have shown conflicting results. We aimed to evaluate the association between obesity and migraine in ELSA-Brasil, a cohort study of 15,105 individuals aged 35-74 years. METHODS: We assessed migraine using a validated questionnaire based on International Headache Society criteria and anthropometric measurements using standard techniques. Migraine was categorized as daily and non-daily. World Health Organization criteria were used to categorize overweight, obesity and abdominal obesity (AbO). We performed a cross-sectional analysis using multivariate logistic regression models to study the association between migraine and obesity (body mass index (BMI) >= 30 kg/m(2)), compared to controls without migraine. RESULTS: We found an association between daily migraine and obesity (odds ratio (OR) 1.86; 95% confidence interval (95% CI): 1.12-3.09). Although the presence of AbO was not associated with migraine, interaction models showed that the association between obesity and daily migraine remained strong only in the absence of AbO diagnosis, notably in individuals aged 35-49 years. DISCUSSION: In our large sample of individuals aged 35 years or older, obesity, but not AbO, was associated with daily migraine. AbO influenced the association between BMI and daily migraine in migraineurs aged 35-49 years. PMID- 25115843 TI - Validation of an extended French version of ID MigraineTM as a migraine-screening tool. AB - INTRODUCTION: Migraine has a considerable social, economic, physical and emotional burden but remains underdiagnosed and undertreated. A specific migraine screening tool could help remove barriers to health care and be an attractive instrument for epidemiological studies. The objective of this work was to assess the validity of an extended French version of ID MigraineTM as a migraine screening tool. METHODS: Sixty-seven subjects from the NESCaV study (2010-2012) completed the migraine screen and were diagnosed by a neurologist specializing in headache medicine using the International Classification of Headache Disorders, 2nd edition criteria (gold standard). Agreement between the two diagnoses was evaluated by Cohen kappa coefficient (kappa). Sensitivity, specificity and predictive values of the migraine screen were calculated. RESULTS: Migraine was diagnosed in 21 (31.3%) of the 67 subjects according to the screening tool and in 24 (35.8%) by the neurologist (kappa = 0.90). The prevalence of migraine was unrelated to age, gender, education and perception of financial resources. Sensitivity and specificity of the screen were 87.5% and 100%, respectively. The screen prevalence of migraine with aura was 10.4% (sensitivity and specificity: 83.3% and 96.7%, respectively). CONCLUSION: The extended French version of ID MigraineTM (ef-ID Migraine) is a validated tool to screen migraine in French speaking countries. PMID- 25115844 TI - Antiepileptics in migraine prophylaxis: an updated Cochrane review. AB - INTRODUCTION: The efficacy of several antiepileptics in the preventive treatment of episodic migraine in adults has been systematically reviewed. Because many trial reports have been published since then, an updated systematic review was warranted. METHODS: We searched the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE (1966 to January 15, 2013), MEDLINE In-Process (current week, January 15, 2013), and EMBASE (1974 to January 15, 2013) and hand-searched Headache and Cephalalgia through January 2013. Prospective, controlled trials of antiepileptics taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both, were selected. RESULTS: Mean headache frequency on topiramate and sodium valproate is significantly lower than placebo. Likewise, topiramate and divalproex demonstrated favorable results for the proportion of subjects with >= 50% reduction of migraine attacks. For topiramate, 100 mg and 200 mg outperformed 50 mg, but this was paralleled by a higher adverse event rate. For valproate/divalproex, a dose-effect correlation could not be established. There was no unequivocal evidence of efficacy for any of the other antiepileptics. CONCLUSION: Topiramate, sodium valproate and divalproex are effective prophylactic treatments for episodic migraine in adults. In contrast to previous reports, there is insufficient evidence to further support the use of gabapentin. PMID- 25115840 TI - Thromboembolic complications in inflammatory bowel disease. AB - Patients with inflammatory bowel disease (IBD) have a 1.5-3.5-fold higher risk of thromboembolism when compared to the non-IBD population and the risk is much more prominent at the time of a flare. Arterial thromboembolism (ischemic stroke, focal white matter ischemia, cardiac ischemia, peripheral vascular disease and mesenteric ischemia) and venous thromboembolism (deep vein thrombosis and pulmonary embolism, cerebral venous sinus thrombosis, retinal, hepatic, portal and mesenteric vein thromboses) belong to the group of underestimated extraintestinal complications in IBD patients, which are associated with a high morbidity and mortality rate (the overall mortality is as high as 25 % per episode). Thromboembolism occurs in younger patients compared to the non-IBD population and has a high recurrence rate. Multiple risk factors are involved in the etiopathogenesis, but the acquired ones play the key role. Congenital alterations do not occur more frequently in IBD patients when compared to the non IBD population. Standardized guidelines for the prophylaxis of thromboembolism in IBD patients are urgently needed and these should be respected in clinical practice to avoid preventable morbidity and mortality. PMID- 25115846 TI - Prediction and validation of diffusion coefficients in a model drug delivery system using microsecond atomistic molecular dynamics simulation and vapour sorption analysis. AB - Diffusion of small to medium sized molecules in polymeric medical device materials underlies a broad range of public health concerns related to unintended leaching from or uptake into implantable medical devices. However, obtaining accurate diffusion coefficients for such systems at physiological temperature represents a formidable challenge, both experimentally and computationally. While molecular dynamics simulation has been used to accurately predict the diffusion coefficients, D, of a handful of gases in various polymers, this success has not been extended to molecules larger than gases, e.g., condensable vapours, liquids, and drugs. We present atomistic molecular dynamics simulation predictions of diffusion in a model drug eluting system that represent a dramatic improvement in accuracy compared to previous simulation predictions for comparable systems. We find that, for simulations of insufficient duration, sub-diffusive dynamics can lead to dramatic over-prediction of D. We present useful metrics for monitoring the extent of sub-diffusive dynamics and explore how these metrics correlate to error in D. We also identify a relationship between diffusion and fast dynamics in our system, which may serve as a means to more rapidly predict diffusion in slowly diffusing systems. Our work provides important precedent and essential insights for utilizing atomistic molecular dynamics simulations to predict diffusion coefficients of small to medium sized molecules in condensed soft matter systems. PMID- 25115847 TI - Monolithic molecularly imprinted cryogel for lysozyme recognition. AB - The application of molecularly imprinted polymers in the selective adsorption of macromolecules such as proteins by monolithic protein-imprinted columns requires a macroporous structure, which can be provided by cryogelation at low temperature in which the formation of ice crystals gives a porous structure to the molecularly imprinted polymer. In this study, we applied this technique to synthesize lysozyme-imprinted polyacrylamide cryogels containing 8% w/v of total monomers and 0.3% w/v of lysozyme. The synthesized cryogel was sponge-like and elastic with very fast swelling and reshaping properties, showing a swelling ratio of 24.5 +/- 3 and gel fraction yield of about 72%. It showed an imprinting effect of 1.58 and a separation factor of 1.37 for cytochrome c as the competing protein. Adsorption studies on the cryogel revealed that it follows the Langmuir isotherm, with a maximum theoretical adsorption capacity of 36.3 mg lysozyme per gram of cryogel. Additionally, it was shown that a salt-free rebinding solution at low flow rate and pH = 7.0 is favorable for lysozyme rebinding. This kind of monolithic column promises a wide range of application in separation of various biomolecules due to its preparation simplicity, good rebinding characteristics, and macroporosity. PMID- 25115845 TI - Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in K562 cells. AB - Despite considerable efficacy of arsenic trioxide (As2O3) in acute promyelocytic leukemia (APL) treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML), are less sensitive to As2O3 treatment. However, the underlying mechanism is not well understood. Here we show that relative As2O3-resistant K562 cells have significantly lower ROS levels than As2O3-sensitive NB4 cells. We compared the expression of several antioxidant enzymes in these two cell lines and found that peroxiredoxin 1/2/6 and catalase are expressed at high levels in K562 cells. We further investigated the possible role of peroxirdoxin 1/2/6 and catalase in determining the cellular sensitivity to As2O3. Interestingly, knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562 cells to As2O3. On the contrary, knockdown of catalase markedly enhanced As2O3 induced apoptosis. In addition, we provide evidence that overexpression of BCR/ABL cannot increase the expression of PRDX 1/2/6 and catalase. The current study reveals that the functional role of antioxidant enzymes is cellular context and treatment agents dependent; targeting catalase may represent a novel strategy to improve the efficacy of As2O3 in CML treatment. PMID- 25115848 TI - Bright, highly water-soluble triazacyclononane europium complexes to detect ligand binding with time-resolved FRET microscopy. AB - Luminescent europium complexes are used in a broad range of applications as a result of their particular emissive properties. The synthesis and application of bright, highly water-soluble, and negatively charged sulfonic- or carboxylic acid derivatives of para-substituted aryl-alkynyl triazacyclononane complexes are described. Introduction of the charged solubilizing moieties suppresses cellular uptake or adsorption to living cells making them applicable for labeling and performing assays on membrane receptors. These europium complexes are applied to monitor fluorescent ligand binding on cell-surface proteins with time-resolved Forster resonance energy transfer (TR-FRET) assays in plate-based format and using TR-FRET microscopy. PMID- 25115850 TI - Biocatalytic potential of lipase from Staphylococcus sp. MS1 for transesterification of jatropha oil into fatty acid methyl esters. AB - An extracellular lipase producing isolate Staphylococcus sp. MS1 was optimized for lipase production and its biocatalytic potential was assessed. Medium with tributyrin (0.25 %) and without any exogenous inorganic nitrogen source was found to be optimum for lipase production from Staphylococcus sp. MS1. The optimum pH and temperature for lipase production were found to be pH 7 and 37 degrees C respectively, showing lipase activity of 37.91 U. It showed good lipase production at pH 6-8. The lipase was found to be stable in organic solvents like hexane and petroleum ether, showing 98 and 88 % residual activity respectively. The biotransformation using the concentrated enzyme in petroleum ether resulted in the synthesis of fatty acid methyl esters like methyl oleate, methyl palmitate and methyl stearate. Thus, the lipase under study has got the potential to bring about transesterification of oils into methyl esters which can be exploited for various biotechnological applications. PMID- 25115852 TI - Assessment of atrial electromechanical delay and left atrial mechanical functions in patients with psoriasis vulgaris. AB - OBJECTIVES: Increased frequency of atrial fibrillation (AF) has been demonstrated in psoriasis cases. Prolongation of the duration of atrial electromechanical delay (AEMD) is a well-known characteristic of the atrium, which is vulnerable to AF. In the current study, our aims are to investigate AEMD durations and mechanical functions of the left atrium (LA) in patients with psoriasis. METHODS: A total of 90 patients, 45 with psoriasis vulgaris and 45 as the control group, were included in the study. Atrial electromechanical coupling (PA) and intra- and inter-atrial electromechanical delay (IA-AEMD) were measured with tissue Doppler echocardiography. P-wave dispersion (PWD) was calculated from the 12-lead electrocardiogram. The severity of the disease was evaluated by the Psoriasis Area and Severity Index. RESULTS: The durations of PA lateral and PA septal were significantly high in the psoriasis group when compared with the control group (47.7 +/- 9.8 vs. 57.1 +/- 8.4 msec, P < 0.001 and 38.6 +/- 9.9 vs. 43.6 +/- 8 msec, P = 0.016, respectively). The durations of IA-AEMD, intra-right electromechanical delay, and intra-left electromechanical delay in the psoriasis group were significantly prolonged compared with the control group (15.2 +/- 4.1 vs. 21.7 +/- 5.6 msec, P < 0.001; 6 +/- 2.5 vs. 8.7 +/- 2.7 msec, P < 0.001; and 9.1 +/- 3.9 vs. 13.5 +/- 5.2 msec, P < 0.001; respectively). PWD was significantly higher in patients with psoriasis vulgaris compared with controls (36.1 +/- 7.9 vs. 40.2 +/- 9.1 msec, P = 0.043). CONCLUSION: In the present study, we found prolongation in the durations of AEMD and PWD in the psoriasis group compared with the control group. These results might be an early predictor of AF and other arrhythmias. PMID- 25115853 TI - Analyte zone sharpening in pressurized capillary electrochromatography based on electrophoretic migration under a heterogeneous field. AB - Significant peak width reductions, or peak height enhancements, of angiotensins were observed when a high voltage was applied to hydrophilic interaction pressurized capillary electrochromatography using gradient elution with mobile phases containing perchloric acid. The investigation using a contactless conductivity detector revealed that perchloric acid was adsorbed on the surface of the stationary phase, when the acetonitrile content in the mobile phase was high, and released from the stationary phase by increasing the water content during a gradient procedure. The released perchloric acid formed a highly concentrated zone moving from the column inlet to the outlet. The electrochromatographic behavior of the analytes, primarily electrophoretic migration, was changed in this zone. As a consequence of the significant variation in migration velocity of the analytes, the sample band width was reduced similar fashion to on-capillary concentration in capillary electrophoresis. Using this result, the reduction of band width and enhancement in separation efficiency was demonstrated in reversed-phase pressurized electrochromatography, in which the conductivity of the mobile phase was significantly altered using a step gradient. The resolution between benzoic acid and 1-naphthalene sulfonic acid was successfully improved from 2.7 to 4.3 by using the band width reduction method based on field-amplified stacking. PMID- 25115849 TI - The potential of transgenic green microalgae; a robust photobioreactor to produce recombinant therapeutic proteins. AB - Microalgae have been used in food, cosmetic, and biofuel industries as a natural source of lipids, vitamins, pigments and antioxidants for a long time. Green microalgae, as potent photobioreactors, can be considered as an economical expression system to produce recombinant therapeutical proteins at large-scale due to low cost of production and scaling-up capitalization owning to the inexpensive medium requirement, fast growth rate, and the ease of manipulation. These microalgae possess all benefit eukaryotic expression systems including the ability of post-translational modifications required for proper folding and stability of active proteins. Among the many items regarded as recombinant protein production, this review compares the different expression systems with green microalgae like Dunaliella by viewing the nuclear/chloroplast transformation challenges/benefits, related selection markers/reporter genes, and crucial factors/strategies affecting the increase of foreign protein expression in microalgae transformants. Some important factors were discussed regarding the increase of protein yielding in microalgae transformants including: transformation-associated genotypic modifications, endogenous regulatory factors, promoters, codon optimization, enhancer elements, and milking of recombinant protein. PMID- 25115854 TI - Carnosine inhibits the proliferation of human gastric cancer SGC-7901 cells through both of the mitochondrial respiration and glycolysis pathways. AB - Carnosine, a naturally occurring dipeptide, has been recently demonstrated to possess anti-tumor activity. However, its underlying mechanism is unclear. In this study, we investigated the effect and mechanism of carnosine on the cell viability and proliferation of the cultured human gastric cancer SGC-7901 cells. Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells cultured with pyruvate have active mitochondria, and depend on mitochondrial oxidative phosphorylation more than glycolysis pathway for generation of ATP. Carnosine markedly decreased the absolute value of mitochondrial ATP-linked respiration, and reduced the maximal oxygen consumption and spare respiratory capacity, which may reduce mitochondrial function correlated with proliferative potential. Simultaneously, carnosine also reduced the extracellular acidification rate and glycolysis of SGC-7901 cells. Our results suggested that carnosine is a potential regulator of energy metabolism of SGC-7901 cells both in the anaerobic and aerobic pathways, and provided a clue for preclinical and clinical evaluation of carnosine for gastric cancer therapy. PMID- 25115858 TI - Synthesis of alpha-aryl esters and nitriles: deaminative coupling of alpha aminoesters and alpha-aminoacetonitriles with arylboronic acids. AB - Transition-metal-free synthesis of alpha-aryl esters and nitriles using arylboronic acids with alpha-aminoesters and alpha-aminoacetonitriles, respectively, as the starting materials has been developed. The reaction represents a rare case of converting C(sp(3))-N bonds into C(sp(3))-C(sp(2)) bonds. The reaction conditions are mild, demonstrate good functional-group tolerance, and can be scaled up. PMID- 25115857 TI - Improving post-stroke dysphagia outcomes through a standardized and multidisciplinary protocol: an exploratory cohort study. AB - Stroke is a major cause of dysphagia. Few studies to date have reported on standardized multidisciplinary protocolized approaches to the management of post stroke dysphagia. The aim of this retrospective cohort study was to evaluate the impact of a standardized multidisciplinary protocol on clinical outcomes in patients with post-stroke dysphagia. We performed retrospective chart reviews of patients with post-stroke dysphagia admitted to the neurological ward of Verona University Hospital from 2004 to 2008. Outcomes after usual treatment for dysphagia (T- group) were compared versus outcomes after treatment under a standardized diagnostic and rehabilitative multidisciplinary protocol (T+ group). Outcome measures were death, pneumonia on X-ray, need for respiratory support, and proportion of patients on tube feeding at discharge. Of the 378 patients admitted with stroke, 84 had dysphagia and were enrolled in the study. A significantly lower risk of in-hospital death (odds ratio [OR] 0.20 [0.53-0.78]), pneumonia (OR 0.33 [0.10-1.03]), need for respiratory support (OR 0.48 [0.14 1.66]), and tube feeding at discharge (OR 0.30 [0.09-0.91]) was recorded for the T+ group (N = 39) as compared to the T- group (N = 45). The adjusted OR showed no difference between the two groups for in-hospital death and tube feeding at discharge. Use of a standardized multidisciplinary protocolized approach to the management of post-stroke dysphagia may significantly reduce rates of aspiration pneumonia, in-hospital mortality, and tube feeding in dysphagic stroke survivors. Consistent with the study's exploratory purposes, our findings suggest that the multidisciplinary protocol applied in this study offers an effective model of management of post-stroke dysphagia. PMID- 25115856 TI - Functional swallowing outcomes in nasopharyngeal cancer treated with IMRT at 6 to 42 months post-radiotherapy. AB - We sought to evaluate the swallowing function of 18 patients surviving nasopharyngeal cancer, who had been treated using an intensity-modulated radiotherapy (IMRT) protocol designed to minimise functional impairment. We compared the outcomes of a patient-reported oral function score with fiberoptic endoscopic examination of swallow (FEES), Australian Therapy Outcome Measures (AusTOMs) and a measure of trismus. While all patients returned to a fully oral diet, there was ongoing swallow dysfunction characterised by bolus residue and delay, but no aspiration. Dysphagia was of mild or moderate severity on all measures, generally because of the need for texture modification, impaired bolus transit or dysgeusia. There was xerostomia on self-reported measurement combined with reports of behaviours adaptive to xerostomia on AusTOMs; however, salivary functioning was less impaired on FEES. There was no trismus in this cohort. Our cohort lacked the morbidity experienced by cohorts reported in earlier studies, potentially due to the use of IMRT. PMID- 25115855 TI - Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-kappaB and ERK signaling pathways in BV2 cells. AB - BACKGROUND AND OBJECTIVE: Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra Moore. Recent studies have suggested that TET can reduce the inflammatory response in microglia, but the mechanisms remain unclear. The aim of this study is to investigate whether TET can inhibit lipopolysaccharide (LPS)-induced microglial activation and clarify its possible mechanisms. STUDY DESIGN/MATERIALS AND METHODS: Cell viability assays and cell apoptosis assays were used to determine the working concentrations of TET. Then, BV2 cells were seeded and pretreated with TET for 2 h. LPS was then added and incubated for an additional 24 hours. qRT-PCR and ELISA were used to measure the mRNA or protein levels of IL1beta and TNFalpha. Western blotting was utilized to quantify the expression of CD11b and cell signaling proteins. RESULTS: TET at optimal concentrations (0.1 uM, 0.5 uM or 1 uM) did not affect the cell viability. After TET pretreatment, the levels of IL1beta and TNFalpha (both in transcription and translation) were significantly inhibited in a dose-dependent manner. Further studies indicated that phospho-p65, phospho-IKK, and phospho-ERK 1/2 expression were also suppressed by TET. CONCLUSIONS: Our results indicate that TET can effectively suppress microglial activation and inhibit the production of IL1beta and TNFalpha by regulating the NF-kB and ERK signaling pathways. Together with our previous studies, we suggest that TET would be a promising candidate to effectively suppress overactivated microglia and alleviate neurodegeneration in glaucoma. PMID- 25115860 TI - Different implication of elevated B-type natriuretic peptide level in patients with heart failure with preserved ejection fraction and in those with reduced ejection fraction. AB - BACKGROUND: There have been no reports that show significant direct relationship between echocardiographic parameters and B-type natriuretic peptide (BNP) level. This could be due to the heterogeneous pathophysiology of heart failure and a lack of appropriate echocardiographic parameters. We sought to determine the best echocardiographic parameter that described elevated BNP level in patients with heart failure with and without systolic dysfunction. METHODS AND RESULTS: We studied 111 consecutive heart failure patients. They were divided into patients with heart failure and preserved ejection fraction (HFPEF, n = 61) and that with heart failure and reduced ejection fraction (HFREF, n = 50). Conventional and new echocardiographic parameters including myocardial strains were measured. BNP did not reflect any single echocardiographic parameter in patients with heart failure in total. The ratio of early diastolic transmitral flow velocity and mitral annular velocity had strong positive correlation with BNP level in the HFPEF group but not in the HFREF group. In the group of HFREF, global longitudinal and circumferential strains were positively correlated. Multivariate analysis revealed that predicted factors for BNP value in HFPEF and in HFREF were different. CONCLUSION: High BNP level may indicate high filling pressure when ejection fraction is preserved and may indicate myocardial dysfunction when it is reduced. PMID- 25115862 TI - Interfacial dynamics in foams and emulsions. PMID- 25115861 TI - Topoisomerase 2 is dispensable for the replication and segregation of small yeast artificial chromosomes (YACs). AB - DNA topoisomerases are thought to play a critical role in transcription, replication and recombination as well as in the condensation and segregation of sister duplexes during cell division. Here, we used high-resolution two dimensional agarose gel electrophoresis to study the replication intermediates and final products of small circular and linear minichromosomes of Saccharomyces cerevisiae in the presence and absence of DNA topoisomerase 2. The results obtained confirmed that whereas for circular minichromosomes, catenated sister duplexes accumulated in the absence of topoisomerase 2, linear YACs were able to replicate and segregate regardless of this topoisomerase. The patterns of replication intermediates for circular and linear YACs displayed significant differences suggesting that DNA supercoiling might play a key role in the modulation of replication fork progression. Altogether, this data supports the notion that for linear chromosomes the torsional tension generated by transcription and replication dissipates freely throughout the telomeres. PMID- 25115863 TI - Postoperative complications in bariatric surgery using age and BMI stratification: a study using ACS-NSQIP data. AB - BACKGROUND: Bariatric surgery results in long-term weight loss and significant morbidity reduction. Morbidity and mortality following bariatric surgery remain low and acceptable. This study looks to define the trend of morbidity and mortality as it relates to increasing age and body mass index (BMI) in patients undergoing bariatric surgery. METHODS: We queried the ACS/NSQIP 2010-2011 Public Use File for patients who underwent elective laparoscopic adjustable banding (LAGB), sleeve gastrectomy (LSG) and gastric bypass (LGBP). Total morbidity and 30-day mortality were evaluated. Logistic regression models were created to estimate the effect of increasing age and BMI on morbidity for these bariatric procedures. RESULTS: A total of 20,308 laparoscopic bariatric procedures were reviewed (11617 LGBP, 3069 LSG and 5622 LAGB). Overall mortality and morbidity rates were 0.11 and 3.84%, respectively. The odds of postoperative complications increased by 2% with each additional year of age (OR 1.02, 95% CI 1.02-1.03) and every point increase in BMI (OR 1.02, 95% CI 1.01-1.03). Multiple logistic regression identified COPD, Diabetes, Hypertension, and Dyspnea as major risk factors for postoperative morbidity. Postoperative complications were three times more likely after LGBP (OR 2.87, 95% CI 2.31-3.57) and two times more likely after LSG (OR 2.06, 95% CI 1.57-2.72) when compared to patients undergoing LAGB. CONCLUSION: Morbidity and mortality increase on a predictable trend with increasing age and BMI. There is increased risk of morbidity for stapling procedures when compared to gastric banding, but this must be considered in context of surgical efficacy when choosing a bariatric procedure. These data can be used in preoperative counseling and evaluation of surgical candidacy of bariatric surgical patients. PMID- 25115864 TI - Superior mesenteric artery syndrome following sleeve gastrectomy: case report, review of the literature, and video on technique for surgical correction. AB - Superior mesenteric artery (SMA) syndrome is a rare condition in which the duodenum is compressed between the SMA and aorta. This often occurs following extreme weight loss and has been reported in the bariatric population. We present the first reported case of SMA syndrome following sleeve gastrectomy. The patient underwent laparoscopic duodenojejunostomy and recovered uneventfully. The following is a review of the literature and detailed operative approach in the attached video. PMID- 25115865 TI - Pre-operative opioid analgesia reduces clinical success of laparoscopic gastric electrical stimulation placement in patients with gastroparesis. AB - INTRODUCTION: Gastroparesis is a common chronic and costly disorder for which medical therapy is often unsuccessful. Gastric electrical stimulation (GES) has been used to treat refractory cases, however, response is variable and difficult to predict. This study aims to assess whether pre-operative opioid analgesics (OA) use affects clinical success of GES. METHODS: Records of 128 patients who underwent laparoscopic GES placement from March 2001 to September 2012 were analyzed retrospectively. Data collected included demographics, surgical outcomes, and clinical parameters. Pre- and post-operative opioid analgesic dosing (No = 0 morphine equivalents (ME)/day, Low = 0-40 ME/day, Mid = 41-80 ME/day, High >80 ME/day), as well as clinical symptom assessment was collected for up to 3 years post-operatively. Clinical success was defined as (1) OA reduction of >50 %, (2) maintenance of weight, or (3) symptom improvement. Descriptive statistics were computed for all factors. A p < 0.05 was considered statistically significant. RESULTS: Fifty-three patients were on OA pre operatively compared to 69 patients who were not. Patients not on OA pre operatively were less likely than those on OA pre-op group to be on OA post operatively (p = 0.005); however, there were no differences in weight or symptom improvement. Sub-group analysis of the 53 patients on OA demonstrated significant improvement in clinical symptoms in the low-morphine cohort compared to the mid morphine cohort (p = 0.02), and OA dosing post-operatively in the low-morphine cohort diminished significantly compared to mid- and high-morphine cohort (p = 0.032). There was no significant difference in weight. CONCLUSION: OA dosing pre operatively significantly affects clinical success of GES placement. Criteria for offering GES implantation may need to take OA dosing into consideration. PMID- 25115866 TI - Bottom-up design of small molecules that stimulate exon 10 skipping in mutant MAPT pre-mRNA. AB - One challenge in chemical biology is to develop small molecules that control cellular protein content. The amount and identity of proteins are influenced by the RNAs that encode them; thus, protein content in a cell could be affected by targeting mRNA. However, RNA has been traditionally difficult to target with small molecules. In this report, we describe controlling the protein products of the mutated microtubule-associated protein tau (MAPT) mature mRNA with a small molecule. MAPT mutations in exon 10 are associated with inherited frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), an incurable disease that is directly caused by increased inclusion of exon 10 in MAPT mRNA. Recent studies have shown that mutations within a hairpin at the MAPT exon 10-intron junction decrease the thermodynamic stability of the RNA, increasing binding to U1 snRNP and thus exon 10 inclusion. Therefore, we designed small molecules that bind and stabilize a mutant MAPT by using Inforna, a computational approach based on information about RNA-small-molecule interactions. The optimal compound selectively bound the mutant MAPT hairpin and thermodynamically stabilized its folding, facilitating exon 10 exclusion. PMID- 25115867 TI - Cardiac strain during upright cycle ergometry in adolescent males. AB - Little evidence exists with regard to changes in cardiac strain that occur during submaximal exercise in young males. The aims of the study were to evaluate the changes that occur in longitudinal (L), radial (R), and endocardial circumferential (EC) strain during submaximal upright cycle ergometry and to examine the test-retest reproducibility of these measurements. Fourteen recreationally active, adolescent (age: 17.9 +/- 0.7 years) males volunteered for the study. All subjects underwent an incremental (40 W) submaximal cycle ergometer test. L, R, and EC strain values were obtained using speckle tracking, from two-dimensional B-mode images of the left ventricle (LV) during rest and the initial stages of submaximal exercise (40 and 80 W). The average of 6 LV segments was used to determine both peak wall deformation (%) and the time to peak deformation (ms). There was a statistically (P < 0.05) significant increase from rest to submaximal exercise for peak deformation for L, R, and EC strain. There was a statistically significant (P < 0.05) decrease from rest to submaximal exercise for time to peak for L and R and EC strain and between submaximal workloads for time to peak for L strain and EC strain. Coefficients of variation demonstrated reproducibility for upright strain and strain rate measurements similar to published supine measurements. This study has demonstrated that changes in left ventricular wall deformation (L, R and EC strain) that occur during the transition from rest to submaximal exercise can be reliably measured and confirm that a healthy LV has a hyperdynamic response to exercise. PMID- 25115868 TI - Cardiovascular disease-related parameters and oxidative stress in SHROB rats, a model for metabolic syndrome. AB - SHROB rats have been suggested as a model for metabolic syndrome (MetS) as a situation prior to the onset of CVD or type-2 diabetes, but information on descriptive biochemical parameters for this model is limited. Here, we extensively evaluate parameters related to CVD and oxidative stress (OS) in SHROB rats. SHROB rats were monitored for 15 weeks and compared to a control group of Wistar rats. Body weight was recorded weekly. At the end of the study, parameters related to CVD and OS were evaluated in plasma, urine and different organs. SHROB rats presented statistically significant differences from Wistar rats in CVD risk factors: total cholesterol, LDL-cholesterol, triglycerides, apoA1, apoB100, abdominal fat, insulin, blood pressure, C-reactive protein, ICAM-1 and PAI-1. In adipose tissue, liver and brain, the endogenous antioxidant systems were activated, yet there was no significant oxidative damage to lipids (MDA) or proteins (carbonylation). We conclude that SHROB rats present significant alterations in parameters related to inflammation, endothelial dysfunction, thrombotic activity, insulin resistance and OS measured in plasma as well as enhanced redox defence systems in vital organs that will be useful as markers of MetS and CVD for nutrition interventions. PMID- 25115869 TI - Evaluation of [111In]-labeled zinc-dipicolylamine tracers for SPECT imaging of bacterial infection. AB - PURPOSE: This study prepared three structurally related zinc-dipicolylamine (ZnDPA) tracers with [(111)In] labels and conducted biodistribution and single photon emission computed tomography/computed tomography (SPECT/CT) imaging studies of a mouse leg infection model. PROCEDURES: Two monovalent tracers, ZnDPA [(111)In]DTPA and ZnDPA-[(111)In]DOTA, each with a single zinc-dipicolylamine targeting unit, and a divalent tracer, Bis(ZnDPA)-[(111)In]DTPA, with two zinc dipicolylamine units were prepared. Organ biodistribution and SPECT and CT imaging studies were performed on living mice with a leg infection created by injection of clinically relevant Gram positive Streptococcus pyogenes. Fluorescent and luminescent Eu(3+)-labeled versions of these tracers were also prepared and used to measure relative affinity for the exterior membrane surface of bacterial cells and mimics of healthy mammalian cells. RESULTS: All three (111)In-labeled radiotracers were prepared with a radiopurity of >90 %. The biodistribution studies showed that the two monovalent tracers were cleared from the body through the liver and kidney, with retained percentage injected dose for all organs of <8 % at 20 h and infected leg target to non-target ratio (T/NT) ratio of <=3.0. Clearance of the divalent tracer from the bloodstream was slower and primarily through the liver, with a retained percentage injected dose for all organs <37 % at 20 h and T/NT ratio rising to 6.2 after 20 h. The SPECT/CT imaging indicated the same large difference in tracer pharmacokinetics and higher accumulation of the divalent tracer at the site of infection. CONCLUSIONS: All three [(111)In]-ZnDPA tracers selectively targeted the site of a clinically relevant mouse infection model that could not be discerned by visual external inspection of the living animal. The highest target selectivity, observed with a divalent tracer equipped with two zinc-dipicolylamine targeting units, compares quite favorably with the imaging selectivities previously reported for other nuclear tracers that target bacterial cell surfaces. The tracer pharmacokinetics depended heavily on tracer molecular structure suggesting that it may be possible to rapidly fine tune the structural properties for optimized in vivo imaging performance and clinical translation. PMID- 25115871 TI - Evaluation of intravenous peramivir for treatment of influenza in hospitalized patients. AB - BACKGROUND: Seasonal influenza causes >200 000 annual hospitalizations in the United States. Current antiviral treatment options are limited to oral or inhaled agents. There is an urgent unmet need for intravenous antiviral treatments. METHODS: Patients hospitalized with suspected influenza were randomized to 5-day treatment with intravenous peramivir (600 mg once daily) or placebo; all received the institution's standard of care (SOC) treatment. Time to clinical resolution and change in viral shedding in nasopharyngeal specimens were the primary and key secondary end points. RESULTS: Influenza infection was confirmed in 338 of 405 enrolled patients. At the time of a preplanned interim analysis, the primary efficacy analysis population comprised 121 patients who did not receive a concurrent neuraminidase inhibitor as part of the SOC. The median (95% confidence interval) time to clinical resolution was 42.5 (34.0-57.9) hours for peramivir versus 49.5 (40.0-61.9) hours for placebo (P = .97). A larger treatment effect was observed in patients with history of symptoms <48 hours or admitted to an intensive care unit. Greater reductions in viral shedding, based on median tissue culture infective dose, were observed in patients who received peramivir than in placebo recipients, although this difference was not statistically significant. The incidence and severity of adverse events and laboratory abnormalities were similar between the 2 treatment groups. The study was terminated for futility after a preplanned interim analysis. CONCLUSIONS: A significant clinical benefit was not demonstrated for peramivir plus SOC compared with placebo plus SOC. Peramivir was generally safe and well tolerated. These findings highlight the challenges in designing studies to evaluate influenza antiviral agents in a hospitalized setting. Clinical Trials Registration. NCT00958776. PMID- 25115872 TI - Added value of the emm-cluster typing system to analyze group A Streptococcus epidemiology in high-income settings. PMID- 25115870 TI - The South Asian genome. AB - The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians. PMID- 25115873 TI - Using clinicians' search query data to monitor influenza epidemics. AB - Search query information from a clinician's database, UpToDate, is shown to predict influenza epidemics in the United States in a timely manner. Our results show that digital disease surveillance tools based on experts' databases may be able to provide an alternative, reliable, and stable signal for accurate predictions of influenza outbreaks. PMID- 25115874 TI - Irritable bowel syndrome and chronic fatigue 6 years after giardia infection: a controlled prospective cohort study. AB - BACKGROUND: Functional gastrointestinal disorders and fatigue may follow acute infections. This study aimed to estimate the persistence, prevalence, and risk of irritable bowel syndrome and chronic fatigue 6 years after Giardia infection. METHODS: We performed a controlled prospective study of a cohort of 1252 individuals who had laboratory-confirmed Giardia infection during a waterborne outbreak in 2004. In total, 748 cohort cases (exposed) and 878 matched controls responded to a postal questionnaire 6 years later (in 2010). Responses were compared to data from the same cohort 3 years before (in 2007). RESULTS: The prevalences of irritable bowel syndrome (39.4%) by Rome III criteria and chronic fatigue (30.8%) in the exposed group 6 years after giardiasis were significantly elevated compared with controls, with adjusted relative risks (RRs) of 3.4 (95% confidence interval [CI], 2.9-3.9) and 2.9 (95% CI, 2.3-3.4), respectively. In the exposed group, the prevalence of irritable bowel syndrome decreased by 6.7% (RR, 0.85 [95% CI, .77-.93]), whereas the prevalence of chronic fatigue decreased by 15.3% from 3 to 6 years after Giardia infection (RR, 0.69 [95% CI, .62-.77]). Giardia exposure was a significant risk factor for persistence of both conditions, and increasing age was a risk factor for persisting chronic fatigue. CONCLUSIONS: Giardia infection in a nonendemic setting is associated with an increased risk for irritable bowel syndrome and chronic fatigue 6 years later. The prevalences of both conditions decrease over time, indicating that this intestinal protozoan parasite may elicit very long-term, but slowly self limiting, complications. PMID- 25115876 TI - Transplantation in autosomal recessive polycystic kidney disease: liver and/or kidney? AB - Autosomal recessive polycystic kidney disease (ARPKD) is characterized by enlarged kidneys with dilated collecting ducts and congenital hepatic fibrosis. There is a variable rate of progression of kidney and liver disease. Portal hypertension and Caroli's disease occur from liver involvement that contributes to morbidity and mortality. Approximately 40 % of patients have a severe disease phenotype leading to rapid onset of end-stage kidney disease (ESKD) and signs of portal hypertension and the rest may have predominant involvement of either the kidney or liver. It is important for the physician to establish the extent of organ involvement before deciding on the ultimate plan of management, especially when transplantation is required. Isolated renal transplantation can be considered when liver involvement is minimal. If hepatobiliary disease is prominent, and kidney function is preserved, management options are based on individual characteristics. In the presence of significant liver disease and ESKD, consideration should be given to combined liver kidney transplantation, which can be beneficial in eliminating the consequences of both kidney and liver disease. However, this is a complex surgical procedure that needs to be performed at experienced transplant centers. Improvement in surgical techniques has considerably improved short-term graft survival with the added advantage of the liver offering immunologic protection to the kidney allograft. PMID- 25115875 TI - Peri-operative kidney injury and long-term chronic kidney disease following orthotopic heart transplantation in children. AB - Significant advances in cardiac intensive care including extracorporeal life support have enabled children with complex congenital heart disease and end-stage heart failure to be supported while awaiting transplantation. With an increasing number of survivors after heart transplantation in children, the complications from long-term immunosuppression, including renal insufficiency, are becoming more apparent. Severe renal dysfunction after heart transplant is defined by a serum creatinine level >2.5 mg/dL (221 MUmol/L), and/or need for dialysis or renal transplant. The degree of renal dysfunction is variable and is progressive over time. About 3-10 % of heart transplant recipients will go on to develop severe renal dysfunction within the first 10 years post-transplantation. Multiple risk factors for chronic kidney disease post-transplant have been identified, which include pre-transplant worsening renal function, recipient demographics and morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin inhibitors. Renal insufficiency increases the risk of post-transplant morbidity and mortality. Hence, screening for renal dysfunction pre-, peri- and post transplantation is important. Early and timely detection of renal insufficiency may help minimize renal insults, and allow prompt implementation of renoprotective strategies. Close monitoring and pre-emptive management of renal dysfunction is an integral aspect of peri-transplant and subsequent post transplant long-term care. PMID- 25115883 TI - Tools in a clinical information system supporting clinical trials at a Swiss University Hospital. AB - BACKGROUND: Issues concerning inadequate source data of clinical trials rank second in the most common findings by regulatory authorities. The increasing use of electronic clinical information systems by healthcare providers offers an opportunity to facilitate and improve the conduct of clinical trials and the source documentation. We report on a number of tools implemented into the clinical information system of a university hospital to support clinical research. METHODS: In 2011/2012, a set of tools was developed in the clinical information system of the University Hospital Zurich to support clinical research, including (1) a trial registry for documenting metadata on the clinical trials conducted at the hospital, (2) a patient-trial-assignment-tool to tag patients in the electronic medical charts as participants of specific trials, (3) medical record templates for the documentation of study visits and trial-related procedures, (4) online queries on trials and trial participants, (5) access to the electronic medical records for clinical monitors, (6) an alerting tool to notify of hospital admissions of trial participants, (7) queries to identify potentially eligible patients in the planning phase as trial feasibility checks and during the trial as recruitment support, and (8) order sets to facilitate the complete and accurate performance of study visit procedures. RESULTS: The number of approximately 100 new registrations per year in the voluntary trial registry in the clinical information system now matches the numbers of the existing mandatory trial registry of the hospital. Likewise, the yearly numbers of patients tagged as trial participants as well as the use of the standardized trial record templates increased to 2408 documented trial enrolments and 190 reports generated/month in the year 2013. Accounts for 32 clinical monitors have been established in the first 2 years monitoring a total of 49 trials in 16 clinical departments. A total of 15 months after adding the optional feature of hospital admission alerts of trial participants, 107 running trials have activated this option, including 48 out of 97 studies (49.5%) registered in the year 2013, generating approximately 85 alerts per month. CONCLUSIONS: The popularity of the presented tools in the clinical information system illustrates their potential to facilitate the conduct of clinical trials. The tools also allow for enhanced transparency on trials conducted at the hospital. Future studies on monitoring and inspection findings will have to evaluate their impact on quality and safety. PMID- 25115881 TI - Postnatal hyperoxia exposure differentially affects hepatocytes and liver haemopoietic cells in newborn rats. AB - Premature newborns are frequently exposed to hyperoxic conditions and experimental data indicate modulation of liver metabolism by hyperoxia in the first postnatal period. Conversely, nothing is known about possible modulation of growth factors and signaling molecules involved in other hyperoxic responses and no data are available about the effects of hyperoxia in postnatal liver haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1alpha (HIF-1alpha), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB). Experimental design of the study involved exposure of newborn rats to room air (controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the first two postnatal weeks. Immunohistochemical and Western blot analyses were performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression and decreased VEGF expression. Reduced content in reticular fibers was found in moderate and severe hyperoxia. Some other changes were specifically produced in hepatocytes by moderate hyperoxia, i.e., upregulation of HIF-1alpha and downregulation of eNOS and NF-kB. Postnatal severe hyperoxia exposure increased liver haemopoiesis and upregulated the expression of VEGF (both moderate and severe hyperoxia) and eNOS (severe hyperoxia) in haemopoietic cells. In conclusion, our study showed different effects of hyperoxia on hepatocytes and haemopoietic cells and differential involvement of the above factors. The involvement of VEGF and eNOS in the liver haemopoietic response to hyperoxia may be hypothesized. PMID- 25115884 TI - Making data from clinical trials available. PMID- 25115882 TI - The transitioning from trials to extended follow-up studies. AB - BACKGROUND: Investigators may elect to extend follow-up of participants enrolled in a randomized clinical trial after the trial comes to its planned end. The additional follow-up may be initiated to learn about longer term effects of treatments, including adverse events, costs related to treatment, or for reasons unrelated to treatment such as to observe the natural course of the disease using the established cohort from the trial. PURPOSE: We examine transitioning from trials to extended follow-up studies when the goal of additional follow-up is to observe longer term treatment effects. METHODS: We conducted a literature search in selected journals from 2000 to 2012 to identify trials that extended follow-up for the purpose of studying longer term treatment effects and extracted information on the operational and logistical issues in the transition. We also draw experience from three trials coordinated by the Johns Hopkins Coordinating Centers that made transitions to extended follow-up: the Alzheimer's Disease Anti inflammatory Prevention Trial, Multicenter Uveitis Steroid Treatment trial, and Childhood Asthma Management Program. RESULTS: Transitions are not uncommon in multicenter clinical trials, even in trials that continued to the planned end of the trial. Transitioning usually necessitates new participant consents. If study infrastructure is not maintained during the transition, participants will be lost and re-establishing the staff and facilities will be costly. Merging data from the trial and follow-up study can be complicated by changes in data collection measures and schedules. LIMITATIONS: Our discussion and recommendations are limited to issues that we have experienced in transitions from trials to follow up studies. DISCUSSION: We discuss issues such as maintaining funding, institutional review board and consent requirements, contacting participants, and combining data from the trial and follow-up phases. We conclude with a list of recommendations to facilitate transitions from a trial to an extended follow-up study. PMID- 25115885 TI - Trigeminal induced arousals during human sleep. AB - BACKGROUND: Arousals caused by external stimuli during human sleep have been studied for most of the sensorial systems. It could be shown that a pure nasal trigeminal stimulus leads to arousals during sleep. The frequency of arousals increases dependent on the stimulus concentration. The aim of the study was to evaluate the influence of different stimulus durations on arousal frequency during different sleep stages. METHODS: Ten young healthy volunteers with 20 nights of polysomnography were included in the study. Pure trigeminal stimulation with both different concentrations of CO2 (0, 10, 20, 40% v/v) and different stimulus durations (1, 3, 5, and 10 s) were applied during different sleep stages to the volunteers using an olfactometer. The application was performed during different sleep stages (light sleep, deep sleep, REM sleep). RESULTS: The number of arousals increased with rising stimulus duration and stimulus concentration during each sleep stage. CONCLUSION: Trigeminal stimuli during sleep led to arousals in dose- and time-dependent manner. PMID- 25115886 TI - Accuracy of a novel auto-CPAP device to evaluate the residual apnea-hypopnea index in patients with obstructive sleep apnea. AB - BACKGROUND: Patients under treatment with continuous positive airway pressure (CPAP) may have residual sleep apnea (RSA). OBJECTIVE: The main objective of our study was to evaluate a novel auto-CPAP for the diagnosis of RSA. METHODS: All patients referred to the sleep laboratory to undergo CPAP polysomnography were evaluated. Patients treated with oxygen or noninvasive ventilation and split night polysomnography (PSG), PSG with artifacts, or total sleep time less than 180 min were excluded. The PSG was manually analyzed before generating the automatic report from auto-CPAP. PSG variables (respiratory disturbance index (RDI), obstructive apnea index, hypopnea index, and central apnea index) were compared with their counterparts from auto-CPAP through Bland-Altman plots and intraclass correlation coefficient. The diagnostic accuracy of autoscoring from auto-CPAP using different cutoff points of RDI (>=5 and 10) was evaluated by the receiver operating characteristics (ROCs) curve. RESULTS: The study included 114 patients (24 women; mean age and BMI, 59 years old and 33 kg/m(2); RDI and apnea/hypopnea index (AHI)-auto median, 5 and 2, respectively). The average difference between the AHI-auto and the RDI was -3.5 +/- 3.9. The intraclass correlation coefficient (ICC) between the total number of central apneas, obstructive, and hypopneas between the PSG and the auto-CPAP were 0.69, 0.16, and 0.15, respectively. An AHI-auto >2 (RDI >= 5) or >4 (RDI >= 10) had an area under the ROC curve, sensitivity, specificity, positive likelihood ratio, and negative for diagnosis of residual sleep apnea of 0.84/0.89, 84/81%, 82/91%, 4.5/9.5, and 0.22/0.2, respectively. CONCLUSIONS: The automatic analysis from auto-CPAP (S9 Autoset) showed a good diagnostic accuracy to identify residual sleep apnea. The absolute agreement between PSG and auto-CPAP to classify the respiratory events correctly varied from very low (obstructive apneas, hypopneas) to moderate (central apneas). PMID- 25115888 TI - Genetic studies reveal an unexpected negative regulatory role for Jak2 in thrombopoiesis. AB - JAK inhibitor treatment is limited by the variable development of anemia and thrombocytopenia thought to be due to on-target JAK2 inhibition. We evaluated the impact of Jak2 deletion in platelets (PLTs) and megakaryocytes (MKs) on blood counts, stem/progenitor cells, and Jak-Stat signaling. Pf4-Cre-mediated Jak2 deletion in PLTs and MKs did not compromise PLT formation but caused thrombocytosis, and resulted in expansion of MK progenitors and Lin(-)Sca1(+)Kit+ cells. Serum thrombopoietin (TPO) was maintained at normal levels in Pf4-Cre positive Jak2(f/f) mice, consistent with reduced internalization/turnover by Jak2 deficient PLTs. These data demonstrate that Jak2 in terminal megakaryopoiesis is not required for PLT production, and that Jak2 loss in PLTs and MKs results in non-autonomous expansion of stem/progenitors and of MKs and PLTs via dysregulated TPO turnover. This suggests that the thrombocytopenia frequently seen with JAK inhibitor treatment is not due to JAK2 inhibition in PLTs and MKs, but rather due to JAK2 inhibition in stem/progenitor cells. PMID- 25115887 TI - Src family kinases: at the forefront of platelet activation. AB - Src family kinases (SFKs) play a central role in mediating the rapid response of platelets to vascular injury. They transmit activation signals from a diverse repertoire of platelet surface receptors, including the integrin alphaIIbbeta3, the immunoreceptor tyrosine-based activation motif-containing collagen receptor complex GPVI-FcR gamma-chain, and the von Willebrand factor receptor complex GPIb IX-V, which are essential for thrombus growth and stability. Ligand-mediated clustering of these receptors triggers an increase in SFK activity and downstream tyrosine phosphorylation of enzymes, adaptors, and cytoskeletal proteins that collectively propagate the signal and coordinate platelet activation. A growing body of evidence has established that SFKs also contribute to Gq- and Gi-coupled receptor signaling that synergizes with primary activation signals to maximally activate platelets and render them prothrombotic. Interestingly, SFKs concomitantly activate inhibitory pathways that limit platelet activation and thrombus size. In this review, we discuss past discoveries that laid the foundation for this fundamental area of platelet signal transduction, recent progress in our understanding of the distinct and overlapping functions of SFKs in platelets, and new avenues of research into mechanisms of SFK regulation. We also highlight the thrombotic and hemostatic consequences of targeting platelet SFKs. PMID- 25115890 TI - A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. AB - The kidney is involved in 70% of patients with immunoglobulin light-chain (AL) amyloidosis, but little is known on progression or reversibility of renal involvement, and criteria for renal response have never been validated. Newly diagnosed patients from the Pavia (n = 461, testing cohort) and Heidelberg (n = 271, validation cohort) centers were included. Proteinuria >5 g/24 h and estimated glomerular filtration rate (eGFR) <50 mL/min predicted progression to dialysis best. Proteinuria below and eGFR above the thresholds indicated low risk (0 and 4% at 3 years in the testing and validation cohorts, respectively). High proteinuria and low eGFR indicated high risk (60% and 85% at 3 years). At 6 months, a >=25% eGFR decrease predicted poor renal survival in both cohorts and was adopted as criterion for renal progression. A decrease in proteinuria by >=30% or below 0.5 g/24 h without renal progression was the criterion for renal response, being associated with longer renal survival in the testing and validation populations. Hematologic very good partial or complete remission at 6 months improved renal outcome in both populations. We identified and validated a staging system for renal involvement and criteria for early assessment of renal response and progression in AL amyloidosis that should be used in clinical practice and trial design. PMID- 25115891 TI - KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL. AB - We analyzed the influence of donor killer-cell immunoglobulin-like receptor (KIR) gene haplotypes on the risk for relapse and the probability of event-free survival (EFS) in children with acute lymphoblastic leukemia who received human leukocyte antigen-haploidentical transplantation of ex vivo T-cell-depleted peripheral blood stem cells. The KIR gene haplotype was evaluated in 85 donors, and the KIR B content score was determined in the 63 KIR haplotype B donors. Patients transplanted from a KIR haplotype B donor had a significantly better EFS than those transplanted from a KIR haplotype A donor (50.6% vs 29.5%, respectively; P = .033). Moreover, a high donor KIR B-content score was associated with a significantly reduced risk for relapse (Log-rank test for trend, P = .026). These data indicate that KIR genotyping should be included in the donor selection algorithm for haploidentical transplantation in children with acute lymphoblastic leukemia with the aim of choosing, whenever possible, a KIR haplotype B donor with a high KIR B-content score. PMID- 25115892 TI - Antiemetic therapy in Asia Pacific countries for patients receiving moderately and highly emetogenic chemotherapy--a descriptive analysis of practice patterns, antiemetic quality of care, and use of antiemetic guidelines. AB - PURPOSE: This paper reports prescribing patterns for prophylaxis of chemotherapy induced nausea and vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. METHODS: In a prospective noninterventional study, 31 sites in Australia, China, India, Singapore, South Korea, and Taiwan recorded details of CINV prophylaxis for the acute phase (first 24 h) and delayed phase (days 2-5) after single-day HEC or MEC for adult patients. Additional information on CINV prophylactic medications was collected from 6-day patient diaries. Primary antiemetic therapies were defined as corticosteroids, the 5-hydroxytryptamine-3 receptor antagonists (5HT3-RAs), and neurokinin-1 receptor antagonists (NK1-RAs). RESULTS: Evaluable patients in cycle 1 numbered 648 (318 [49%] HEC and 330 [51%] MEC) of mean (SD) age of 56 (12) years, including 58% women. For the acute phase after HEC, overall (and country range), 96% (91-100%) of patients received a 5HT3-RA, 87% (70-100%) a corticosteroid, and 43% (0-91%) an NK1-RA. CINV prophylaxis for the HEC delayed phase was more variable: including 22% (7-65%) 5HT3-RA, 52% (12-93%) corticosteroid, and 46% (0-88%) NK1-RA. For the MEC acute phase, 97% (87-100%) of patients received 5HT3-RA and 86% (73-97%) a corticosteroid. For the MEC delayed phase, 201 patients (61%) received a primary antiemetic, including 5HT3-RA (41%), corticosteroid (37%), and/or NK1-RA (4%). CONCLUSIONS: The 5HT3-RAs were prescribed consistently in all countries, while prescribing of other antiemetic therapies was variable, and corticosteroids were under-prescribed for CINV prophylaxis, particularly in the delayed phase. PMID- 25115889 TI - The exosome complex establishes a barricade to erythroid maturation. AB - Complex genetic networks control hematopoietic stem cell differentiation into progenitors that give rise to billions of erythrocytes daily. Previously, we described a role for the master regulator of erythropoiesis, GATA-1, in inducing genes encoding components of the autophagy machinery. In this context, the Forkhead transcription factor, Foxo3, amplified GATA-1-mediated transcriptional activation. To determine the scope of the GATA-1/Foxo3 cooperativity, and to develop functional insights, we analyzed the GATA-1/Foxo3-dependent transcriptome in erythroid cells. GATA-1/Foxo3 repressed expression of Exosc8, a pivotal component of the exosome complex, which mediates RNA surveillance and epigenetic regulation. Strikingly, downregulating Exosc8, or additional exosome complex components, in primary erythroid precursor cells induced erythroid cell maturation. Our results demonstrate a new mode of controlling erythropoiesis in which multiple components of the exosome complex are endogenous suppressors of the erythroid developmental program. PMID- 25115893 TI - Rationale and design of the Pan Australasian chemotherapy-induced emesis burden of illness study. AB - BACKGROUND: Preventing and managing chemotherapy-induced nausea and vomiting (CINV) remain important goals. The objective of the Pan Australasian chemotherapy induced emesis burden of illness (PrACTICE) study was to describe the incidence of CINV after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in current clinical practice in Australia and five Asian countries (China, India, Singapore, South Korea, and Taiwan). STUDY DESIGN: This prospective, observational study of CINV was conducted at 31 sites in these six countries from August 2011 through September 2012 and enrolled male and female adult patients (>=18 years of age) naive to HEC and MEC who were scheduled to receive at least two cycles of single-day chemotherapy. The primary effectiveness endpoint was complete response, defined as no vomiting or use of rescue therapy, during chemotherapy cycle 1 in the overall phase (0-120 h), acute phase (0-24 h), and delayed phase (>24-120 h). Study outcomes were analyzed descriptively. Primary outcomes, CINV incidence, and treatment patterns (chemotherapy, CINV prophylaxis, rescue medication prescription, and rescue medication use) were assessed by phase (overall, acute, delayed), by cycle (as appropriate), within and across countries, and by level of chemotherapy emetogenicity (HEC vs. MEC). The impact of CINV in cycle 1 on CINV in cycle 2 was analyzed for all patients with evaluable data for cycle 2. No site-specific analyses were performed. The remainder of this special series of papers reports on the results of this study. PMID- 25115894 TI - The importance of biologically relevant microclimates in habitat suitability assessments. AB - Predicting habitat suitability under climate change is vital to conserving biodiversity. However, current species distribution models rely on coarse scale climate data, whereas fine scale microclimate data may be necessary to assess habitat suitability and generate predictive models. Here, we evaluate disparities between temperature data at the coarse scale from weather stations versus fine scale data measured in microhabitats required for a climate-sensitive mammal, the American pika (Ochotona princeps). We collected two years of temperature data in occupied talus habitats predicted to be suitable (high elevation) and unsuitable (low elevation) by the bioclimatic envelope approach. At low elevations, talus surface and interstitial microclimates drastically differed from ambient temperatures measured on-site and at a nearby weather station. Interstitial talus temperatures were frequently decoupled from high ambient temperatures, resulting in instantaneous disparities of over 30 degrees C between these two measurements. Microhabitat temperatures were also highly heterogeneous, such that temperature measurements within the same patch of talus were not more correlated than measurements at distant patches. An experimental manipulation revealed that vegetation cover may cool the talus surface by up to 10 degrees C during the summer, which may contribute to this spatial heterogeneity. Finally, low elevation microclimates were milder and less variable than typical alpine habitat, suggesting that, counter to species distribution model predictions, these seemingly unsuitable habitats may actually be better refugia for this species under climate change. These results highlight the importance of fine scale microhabitat data in habitat assessments and underscore the notion that some critical refugia may be counterintuitive. PMID- 25115895 TI - Nuclear magnetic resonance relaxivities: investigations of ultrahigh-spin lanthanide clusters from 10 MHz to 1.4 GHz. AB - Paramagnetic relaxation enhancement is often explored in magnetic resonance imaging in terms of contrast agents and in biomolecular nuclear magnetic resonance (NMR) spectroscopy for structure determination. New ultrahigh-spin clusters are investigated with respect to their NMR relaxation properties. As their molecular size and therefore motional correlation times as well as their electronic properties differ significantly from those of conventional contrast agents, questions about a comprehensive characterization arise. The relaxivity was studied by field-dependent longitudinal and transverse NMR relaxometry of aqueous solutions containing Fe(III)(10)Dy(III)(10) ultrahigh-spin clusters (spin ground state 100/2). The high-field limit was extended to 32.9 T by using a 24 MW resistive magnet and an ultrahigh-frequency NMR setup. Interesting relaxation dispersions were observed; the relaxivities increase up to the highest available fields, which indicates a complex interplay of electronic and molecular correlation times. PMID- 25115896 TI - Potential negative ecological effects of corridors. AB - Despite many studies showing that landscape corridors increase dispersal and species richness for disparate taxa, concerns persist that corridors can have unintended negative effects. In particular, some of the same mechanisms that underlie positive effects of corridors on species of conservation interest may also increase the spread and impact of antagonistic species (e.g., predators and pathogens), foster negative effects of edges, increase invasion by exotic species, increase the spread of unwanted disturbances such as fire, or increase population synchrony and thus reduce persistence. We conducted a literature review and meta-analysis to evaluate the prevalence of each of these negative effects. We found no evidence that corridors increase unwanted disturbance or non native species invasion; however, these have not been well-studied concerns (1 and 6 studies, respectively). Other effects of corridors were more often studied and yielded inconsistent results; mean effect sizes were indistinguishable from zero. The effect of edges on abundances of target species was as likely to be positive as negative. Corridors were as likely to have no effect on antagonists or population synchrony as they were to increase those negative effects. We found 3 deficiencies in the literature. First, despite studies on how corridors affect predators, there are few studies of related consequences for prey population size and persistence. Second, properly designed studies of negative corridor effects are needed in natural corridors at scales larger than those achievable in experimental systems. Third, studies are needed to test more targeted hypotheses about when corridor-mediated effects on invasive species or disturbance may be negative for species of management concern. Overall, we found no overarching support for concerns that construction and maintenance of habitat corridors may result in unintended negative consequences. Negative edge effects may be mitigated by widening corridors or softening edges between corridors and the matrix. Other negative effects are relatively small and manageable compared with the large positive effects of facilitating dispersal and increasing diversity of native species. PMID- 25115897 TI - The metabolism and growth of web forums. AB - We view web forums as virtual living organisms feeding on user's clicks and investigate how they grow at the expense of clickstreams. We find that PV(t) (the number of page views in a given time period) and UV(t) (the number of unique visitors in the time period) of the studied forums satisfy the law of the allometric growth, i.e., PV(t) ~ UV(t)((theta). We construct clickstream networks and explain the observed temporal dynamics of networks by the interactions between nodes. We describe the transportation of clickstreams using the function D(i) ~ T(i)(gamma), in which T(i) is the total amount of clickstreams passing through node i and D(i) is the amount of the clickstreams dissipated from i to the environment. It turns out that gamma, an indicator for the efficiency of network dissipation, not only negatively correlates with theta, but also sets the bounds for theta. In particular, 1/gamma > theta when 0 < gamma < 1 and 1/gamma < theta when gamma > 1. Our findings have practical consequences. For example, theta can be used as a measure of the "stickiness" of forums, which quantifies the stable ability of forums to remain users "lock-in" on the forum. Meanwhile, the correlation between gamma and theta provides a method to predict the long term "stickiness" of forums from the clickstream data in a short time period. Finally, we discuss a random walk model that replicates both of the allometric growth PV(t) ~ UV(t)(theta) and the dissipation function D(i) ~ T(gamma)(i). PMID- 25115898 TI - Concentrations and distribution of polybrominated diphenyl ethers (PBDEs) in soils and plants from a deca-BDE manufacturing factory in China. AB - Residues of polybrominated diphenyl ethers (PBDEs), including eight PBDE congeners, were investigated in soils and plants from a deca-BDE manufacturing factory located in the Shandong province of China to evaluate and discuss their pollution level and distribution. Total concentrations in topsoil ranged from 17.0 to 146 MUg g(-1) dry weight (dw) with a mean value of 58.7 MUg g(-1) dw. BDE 209 was the dominant congener in soils, accounting for 55.63-99.27 % of the total PBDEs. Concentrations and congener patterns in soils varied among different soil depths. Concentration levels in topsoil are high and the heavy accumulation in deep soil also can be observed, even for some sites, the concentrations in 50-100 cm depth are higher than in topsoil. In plant samples, total PBDE concentrations and the proportion of BDE-209 were high (69.92-99.10 %). The extent of pollution by PBDEs in the deca-BDE production factory was higher than in other regions, and the environmental risk caused by the production of deca-BDE is of concern. This is the first study to report pollution of PBDEs in soils and plants from the vicinity of a deca-BDE manufacturing factory. PMID- 25115899 TI - Removal of heavy metal species from industrial sludge with the aid of biodegradable iminodisuccinic acid as the chelating ligand. AB - High level of heavy metals in industrial sludge was the obstacle of sludge disposal and resource recycling. In this study, iminodisuccinic acid (IDS), a biodegradable chelating ligand, was used to remove heavy metals from industrial sludge generated from battery industry. The extraction of cadmium, copper, nickel, and zinc from battery sludge with aqueous solution of IDS was studied under various conditions. It was found that removal efficiency greatly depends on pH, chelating agent's concentration, as well as species distribution of metals. The results showed that mildly acidic and neutral systems were not beneficial to remove cadmium. About 68 % of cadmium in the sample was extracted at the molar ratio of IDS to heavy metals 7:1 without pH adjustment (pH 11.5). Copper of 91.3 % and nickel of 90.7 % could be removed by IDS (molar ratio, IDS: metals = 1:1) with 1.2 % phosphoric acid effectively. Removal efficiency of zinc was very low throughout the experiment. Based on the experimental results, IDS could be a potentially useful chelant for heavy metal removal from battery industry sludge. PMID- 25115902 TI - Pollination syndromes in a specialised plant-pollinator interaction: does floral morphology predict pollinators in Calceolaria? AB - Pollination syndromes are defined as suites of floral traits evolved in response to selection imposed by a particular group of pollinators (e.g., butterflies, hummingbirds, bats). Although numerous studies demonstrated their occurrence in plants pollinated by radically different pollinators, it is less known whether it is possible to identify them within species pollinated by one functional pollinator group. In such a framework, we expect floral traits to evolve also in response to pollinator subgroups (e.g., species, genera) within that unique functional group. On this, specialised pollination systems represent appropriate case studies to test such expectations. Calceolaria is a highly diversified plant genus pollinated by oil-collecting bees in genera Centris and Chalepogenus. Variation in floral traits in Calceolaria has recently been suggested to reflect adaptations to pollinator types. However, to date no study has explicitly tested that observation. In this paper, we quantitatively test that hypothesis by evaluating the presence of pollination syndromes within the specialised pollination system formed by several Calceolaria and their insect pollinators. To do so, we use multivariate approaches and explore the structural matching between the morphology of 10 Calceolaria taxa and that of their principal pollinators. Our results identify morphological matching between floral traits related to access to the reward and insect traits involved in oil collection, confirming the presence of pollinator syndromes in Calceolaria. From a general perspective, our findings indicate that the pollination syndrome concept can be also extended to the intra-pollinator group level. PMID- 25115901 TI - Vaniprevir plus peginterferon alfa-2a and ribavirin in treatment-experienced Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase II study. AB - BACKGROUND: Vaniprevir (MK-7009) is a hepatitis C virus (HCV) non-structural 3/4a protease inhibitor which significantly increases virologic response rates in HCV genotype (GT) 1-infected patients when added to peginterferon and ribavirin (PR). METHODS: This was a phase II, multicenter, double-blind, randomized, dose-ranging study in Japanese patients with HCV GT1 infection and previous relapse. Patients received twice daily vaniprevir 100, 300, or 600 mg, or placebo plus PR for 4 weeks then PR alone for 2 weeks. Further treatment with PR was continued up to a maximum of 72 weeks. The primary endpoint was rapid virologic response (RVR; undetectable HCV RNA at treatment week 4). RESULTS: Ninety patients completed 4 weeks of vaniprevir/placebo plus PR. Rates of RVR were significantly higher with vaniprevir compared with placebo (86, 95, and 76 % in the vaniprevir 100-, 300-, and 600-mg arms versus 20 % with control; p<0.001 for all comparisons). Rates of SVR, an exploratory analysis, in the vaniprevir 100-, 300-, 600-mg, and control arms were 95, 100, 100, and 72 %, respectively. No patient had virologic breakthrough or non-response while receiving vaniprevir. There were no serious adverse events (AEs) or discontinuations due to an AE during vaniprevir treatment. Diarrhea and nausea were more common with vaniprevir 600 mg than control or lower vaniprevir doses. CONCLUSION: The addition of vaniprevir to PR was associated with an increase in RVR and SVR. Combined with a generally safe and well-tolerated profile, these data supported the further evaluation of vaniprevir in Japanese patients with HCV GT1 infection (#NCT00880763). PMID- 25115904 TI - Locked-in biomimetic surface gradients that are tunable in size, density and functionalization. AB - Tuneable and stable surface-chemical gradients in supported lipid bilayers (SLBs) hold great promise for a range of applications in biological sensing and screening. Yet, until now, no method has been reported that provides temporal control of SLB gradients. Herein we report on the development of locked-in SLB gradients that can be tuned in space, time and density by applying a process to control lipid phase behaviour, electric field and temperature. Stable gradients of charged Texas-Red-, serine- or biotin-terminated lipids have been prepared. For example, the Texas-Red surface density was varied from 0 to 2 mol %, while the length was varied between several tens to several hundreds of microns. At room temperature the gradients are shown to be stable up to 24 h, while at 60 degrees C the gradients could be erased in 30 min. Covalent and non-covalent chemical modification of the gradients is demonstrated, for example, by FITC, hexahistidine-tagged proteins, and SAv/biotin. The amenability to various (bio)chemistries paves the way for novel SLB-based gradients, useful in sensing, high-throughput screening and for understanding dynamic biological processes. PMID- 25115903 TI - Brain damage in commercial breath-hold divers. AB - BACKGROUND: Acute decompression illness (DCI) involving the brain (Cerebral DCI) is one of the most serious forms of diving-related injuries which may leave residual brain damage. Cerebral DCI occurs in compressed air and in breath-hold divers, likewise. We conducted this study to investigate whether long-term breath hold divers who may be exposed to repeated symptomatic and asymptomatic brain injuries, show brain damage on magnetic resonance imaging (MRI). SUBJECTS AND METHODS: Our study subjects were 12 commercial breath-hold divers (Ama) with long histories of diving work in a district of Japan. We obtained information on their diving practices and the presence or absence of medical problems, especially DCI events. All participants were examined with MRI to determine the prevalence of brain lesions. RESULTS: Out of 12 Ama divers (mean age: 54.9+/-5.1 years), four had histories of cerebral DCI events, and 11 divers demonstrated ischemic lesions of the brain on MRI studies. The lesions were situated in the cortical and/or subcortical area (9 cases), white matters (4 cases), the basal ganglia (4 cases), and the thalamus (1 case). Subdural fluid collections were seen in 2 cases. CONCLUSION: These results suggest that commercial breath-hold divers are at a risk of clinical or subclinical brain injury which may affect the long-term neuropsychological health of divers. PMID- 25115905 TI - Incorporating social and cultural significance of large old trees in conservation policy. AB - In addition to providing key ecological functions, large old trees are a part of a social realm and as such provide numerous social-cultural benefits to people. However, their social and cultural values are often neglected when designing conservation policies and management guidelines. We believe that awareness of large old trees as a part of human identity and cultural heritage is essential when addressing the issue of their decline worldwide. Large old trees provide humans with aesthetic, symbolic, religious, and historic values, as well as concrete tangible benefits, such as leaves, branches, or nuts. In many cultures particularly large trees are treated with reverence. Also, contemporary popular culture utilizes the image of trees as sentient beings and builds on the ancient myths that attribute great powers to large trees. Although the social and cultural role of large old trees is usually not taken into account in conservation, accounting for human-related values of these trees is an important part of conservation policy because it may strengthen conservation by highlighting the potential synergies in protecting ecological and social values. PMID- 25115907 TI - Editor's choice, volume 111. PMID- 25115906 TI - Implantable collamer lens versus iris-fixed phakic intraocular lens implantation to correct myopia: a meta-analysis. AB - This study is a meta-analysis comparing the efficacy, predictability, and safety of correcting myopia via implantation of two types of phakic intraocular lens (PIOLs): the implantable collamer lens (ICL) and iris-fixed PIOL. The Cochrane library, Pubmed, and EMBASE were searched. Study selection, data exclusion, and quality assessment were performed by two independent observers. The pooled relative risk (RR), pooled standardized mean difference (SMD), and their 95% confidence intervals (CIs) were used to compare lenses. Seven studies, involving 511 eyes, were included. The pooled SMD in postoperative uncorrected distance visual acuity (UDVA) comparing ICLs to iris-fixed PIOLs was -0.22 (95% CI, -0.58 to 0.13; P = .22). The pooled RR values of UDVA of 20/20 or better and of 20/40 or better comparing ICLs to iris-fixed PIOLs were 1.15 (95% CI, 0.89 to 1.47; P = .29) and 1.01 (95% CI, 0.95 to 1.08; P = .75), respectively. The pooled RR of loss of best spectacle-corrected visual acuity (BSCVA) and gain in BSCVA comparing ICLs to iris-fixed PIOLs were 1.20 (95% CI, 0.24 to 6.00; P = .82) and 1.14 (95% CI, 0.89 to 1.48; P = .31), respectively. The pooled RR comparing ICLs to iris-fixed PIOLs was 0.78 (95% CI, 0.29 to 2.12; P = .63) for all reported complications and 2.80 (95% CI, 1.04 to 7.52; P = .04) for severe complications. The pooled RR of achieving a result within +/- 0.5 D (diopter) of the intended target comparing ICLs to iris-fixed PIOLs was 1.35 (95% CI, 1.04 to 1.77; P = .03). Overall, there is no significant difference in efficacy between the two types of PIOLs or in safety, except that the ICL is associated with a greater incidence of severe complications, especially anterior subcapsular cataract, primarily in the Version 2 and Version 3 groups. However, ICL has better predictability. PMID- 25115908 TI - Effects of the duration of cold stratification on early life stages of the Mediterranean alpine plant Silene ciliata. AB - Cold stratification provided by snow cover is essential to break seed dormancy in many alpine plant species. The forecast reduction in snow precipitation and snow cover duration in most temperate mountains as a result of global warming could threaten alpine plant populations, especially those at the edge of their species distribution, by altering the dynamics of early life stages. We simulated some effects of a reduction in the snow cover period by manipulating the duration of cold stratification in seeds of Silene ciliata, a Mediterranean alpine specialist. Seeds from three populations distributed along an altitudinal gradient were exposed to different periods of cold stratification (2, 4 and 6 months) in the laboratory and then moved to common garden conditions in a greenhouse. The duration of the cold stratification treatment and population origin significantly affected seed emergence percentage, emergence rate and seedling size, but not the number of seedling leaves. The 6-month and 4-month cold stratification treatments produced higher emergence percentages and faster emergence rates than seeds without cold stratification treatment. No significant cold stratification duration x seed population origin interactions were found, thus differential sensitivity to cold stratification along elevation is not supported. PMID- 25115910 TI - Preventing aspiration during peroral endoscopic myotomy. PMID- 25115909 TI - Invertebrate extracellular phagocyte traps show that chromatin is an ancient defence weapon. AB - Controlled release of chromatin from the nuclei of inflammatory cells is a process that entraps and kills microorganisms in the extracellular environment. Now termed ETosis, it is important for innate immunity in vertebrates. Paradoxically, however, in mammals, it can also contribute to certain pathologies. Here we show that ETosis occurs in several invertebrate species, including, remarkably, an acoelomate. Our findings reveal that the phenomenon is primordial and predates the evolution of the coelom. In invertebrates, the released chromatin participates in defence not only by ensnaring microorganisms and externalizing antibacterial histones together with other haemocyte-derived defence factors, but crucially, also provides the scaffold on which intact haemocytes assemble during encapsulation; a response that sequesters and kills potential pathogens infecting the body cavity. This insight into the early origin of ETosis identifies it as a very ancient process that helps explain some of its detrimental effects in mammals. PMID- 25115911 TI - Effectiveness of low emission zones: large scale analysis of changes in environmental NO2, NO and NOx concentrations in 17 German cities. AB - BACKGROUND: Low Emission Zones (LEZs) are areas where the most polluting vehicles are restricted from entering. The effectiveness of LEZs to lower ambient exposures is under debate. This study focused on LEZs that restricted cars of Euro 1 standard without appropriate retrofitting systems from entering and estimated LEZ effects on NO2, NO, and NOx ( = NO2+NO). METHODS: Continuous half hour and diffuse sampler 4-week average NO2, NO, and NOx concentrations measured inside and outside LEZs in 17 German cities of 6 federal states (2005-2009) were analysed as matched quadruplets (two pairs of simultaneously measured index values inside LEZ and reference values outside LEZ, one pair measured before and one after introducing LEZs with time differences that equal multiples of 364 days) by multiple linear and log-linear fixed-effects regression modelling (covariables: e.g., wind velocity, amount of precipitation, height of inversion base, school holidays, truck-free periods). Additionally, the continuous half hour data was collapsed into 4-week averages and pooled with the diffuse sampler data to perform joint analysis. RESULTS: More than 3,000,000 quadruplets of continuous measurements (half-hour averages) were identified at 38 index and 45 reference stations. Pooling with diffuse sampler data from 15 index and 10 reference stations lead to more than 4,000 quadruplets for joint analyses of 4 week averages. Mean LEZ effects on NO2, NO, and NOx concentrations (reductions) were estimated to be at most -2 ug/m(3) (or -4%). The 4-week averages of NO2 concentrations at index stations after LEZ introduction were 55 ug/m(3) (median and mean values) or 82 ug/m(3) (95th percentile). CONCLUSIONS: This is the first study investigating comprehensively the effectiveness of LEZs to reduce NO2, NO, and NOx concentrations controlling for most relevant potential confounders. Our analyses indicate that there is a statistically significant, but rather small reduction of NO2, NO, and NOx concentrations associated with LEZs. PMID- 25115913 TI - Overlapped sequence types (STs) and serogroups of avian pathogenic (APEC) and human extra-intestinal pathogenic (ExPEC) Escherichia coli isolated in Brazil. AB - Avian pathogenic Escherichia coli (APEC) strains belong to a category that is associated with colibacillosis, a serious illness in the poultry industry worldwide. Additionally, some APEC groups have recently been described as potential zoonotic agents. In this work, we compared APEC strains with extraintestinal pathogenic E. coli (ExPEC) strains isolated from clinical cases of humans with extra-intestinal diseases such as urinary tract infections (UTI) and bacteremia. PCR results showed that genes usually found in the ColV plasmid (tsh, iucA, iss, and hlyF) were associated with APEC strains while fyuA, irp-2, fepC sitDchrom, fimH, crl, csgA, afa, iha, sat, hlyA, hra, cnf1, kpsMTII, clpVSakai and malX were associated with human ExPEC. Both categories shared nine serogroups (O2, O6, O7, O8, O11, O19, O25, O73 and O153) and seven sequence types (ST10, ST88, ST93, ST117, ST131, ST155, ST359, ST648 and ST1011). Interestingly, ST95, which is associated with the zoonotic potential of APEC and is spread in avian E. coli of North America and Europe, was not detected among 76 APEC strains. When the strains were clustered based on the presence of virulence genes, most ExPEC strains (71.7%) were contained in one cluster while most APEC strains (63.2%) segregated to another. In general, the strains showed distinct genetic and fingerprint patterns, but avian and human strains of ST359, or ST23 clonal complex (CC), presented more than 70% of similarity by PFGE. The results demonstrate that some "zoonotic-related" STs (ST117, ST131, ST10CC, ST23CC) are present in Brazil. Also, the presence of moderate fingerprint similarities between ST359 E. coli of avian and human origin indicates that strains of this ST are candidates for having zoonotic potential. PMID- 25115916 TI - Efficacy and safety of lixisenatide in elderly (>=65 years old) and very elderly (>=75 years old) patients with type 2 diabetes: an analysis from the GetGoal phase III programme. AB - BACKGROUND: The objective of this article is to evaluate the pharmacokinetics, efficacy and safety of lixisenatide (subcutaneous injection) in elderly (>=65 years old) and very elderly (>=75 years old) patients with type 2 diabetes mellitus. METHODS: We conducted a phase I, single-centre, open-label study to evaluate the safety and pharmacokinetics of a single lixisenatide 20 ug dose and a pooled analysis of six randomized, placebo-controlled, phase III studies (12 month or 24-month duration) that evaluated glycaemic parameters and safety in patients receiving lixisenatide 20 ug once daily or placebo. RESULTS: The pharmacokinetics study included 36 healthy subjects, including 18 elderly healthy subjects (>=65 years old) and 18 matched young healthy subjects (18-45 years old). The pooled analysis included 3188 patients, including 2565 patients <65 years old and 623 patients >=65 years old (including 79 patients >=75 years old). Mean exposure with lixisenatide 20 ug was ~30% higher in elderly than in young subjects, and the terminal half-life was prolonged by ~1.6 times. Maximum concentration (C(max)) and time to C(max) (t(max)) were comparable in both groups. Equal numbers of elderly and young subjects reported treatment-emergent adverse events, the majority of which were gastrointestinal disorders. In the pooled analysis, lixisenatide 20 ug once daily provided significant reductions in HbA1c versus placebo for all age groups. There was a similar incidence of treatment-emergent adverse events across all age groups (range: 69-73%). The incidence of symptomatic hypoglycaemia was generally comparable between lixisenatide-treated and placebo-treated patients. CONCLUSION: These data suggest that lixisenatide is effective and well tolerated in elderly and very elderly patients with type 2 diabetes mellitus. PMID- 25115915 TI - Assessment, validation and deployment strategy of a two-barcode protocol for facile genotyping of duckweed species. AB - Lemnaceae, commonly called duckweeds, comprise a diverse group of floating aquatic plants that have previously been classified into 37 species based on morphological and physiological criteria. In addition to their unique evolutionary position among angiosperms and their applications in biomonitoring, the potential of duckweeds as a novel sustainable crop for fuel and feed has recently increased interest in the study of their biodiversity and systematics. However, due to their small size and abbreviated structure, accurate typing of duckweeds based on morphology can be challenging. In the past decade, attempts to employ molecular barcoding techniques for species assignment have produced promising results; however, they have yet to be codified into a simple and quantitative protocol. A study that compiles and compares the barcode sequences within all known species of this family would help to establish the fidelity and limits of this DNA-based approach. In this work, we compared the level of conservation between over 100 strains of duckweed for two intergenic barcode sequences derived from the plastid genome. By using over 300 sequences publicly available in the NCBI database, we determined the utility of each of these two barcodes for duckweed species identification. Through sequencing of these barcodes from additional accessions, 30 of the 37 known species of duckweed could be identified with varying levels of confidence using this approach. From our analyses using this reference dataset, we also confirmed two instances where mis assignment of species has likely occurred. Potential strategies for further improving the scope of this technology are discussed. PMID- 25115917 TI - Osteoporotic L1 burst fracture treated by short-segment percutaneous stabilization with cement-augmented screws and kyphoplasty (hybrid technique). PMID- 25115914 TI - TRF1 and TRF2 differentially modulate Rad51-mediated telomeric and nontelomeric displacement loop formation in vitro. AB - A growing body of literature suggests that the homologous recombination/repair (HR) pathway cooperates with components of the shelterin complex to promote both telomere maintenance and nontelomeric HR. This may be due to the ability of both HR and shelterin proteins to promote strand invasion, wherein a single-stranded DNA (ssDNA) substrate base pairs with a homologous double-stranded DNA (dsDNA) template displacing a loop of ssDNA (D-loop). Rad51 recombinase catalyzes D-loop formation during HR, and telomere repeat binding factor 2 (TRF2) catalyzes the formation of a telomeric D-loop that stabilizes a looped structure in telomeric DNA (t-loop) that may facilitate telomere protection. We have characterized this functional interaction in vitro using a fluorescent D-loop assay measuring the incorporation of Cy3-labeled 90-nucleotide telomeric and nontelomeric substrates into telomeric and nontelomeric plasmid templates. We report that preincubation of a telomeric template with TRF2 inhibits the ability of Rad51 to promote telomeric D-loop formation upon preincubation with a telomeric substrate. This suggests Rad51 does not facilitate t-loop formation and suggests a mechanism whereby TRF2 can inhibit HR at telomeres. We also report a TRF2 mutant lacking the dsDNA binding domain promotes Rad51-mediated nontelomeric D-loop formation, possibly explaining how TRF2 promotes nontelomeric HR. Finally, we report telomere repeat binding factor 1 (TRF1) promotes Rad51-mediated telomeric D-loop formation, which may facilitate HR-mediated replication fork restart and explain why TRF1 is required for efficient telomere replication. PMID- 25115918 TI - The NeckPix((c)): development of an evaluation tool for assessing kinesiophobia in subjects with chronic neck pain. AB - PURPOSE: To develop and validate NeckPix((c)), a multi-image instrument for assessing daily activities in the context of pain-related fear, in order to allow its use in patients with chronic neck pain (NP). METHODS: The measure was developed by means of item generation followed by reduction/selection. The psychometric testing included exploratory factor analysis; content validity by investigating clarity, specificity, appropriateness for the target population, relevance and completeness; reliability by internal consistency (Cronbach's alpha) and test-retest stability (intra-class coefficient correlation, ICC); and construct validity by comparing NeckPix with the Tampa Scale of Kinesiophobia (TSK), the Pain Catastrophising Scale (PCS), the Neck Disability Index (NDI) and a Numerical Rating Scale of pain intensity (NRS) (Pearson's correlation). RESULTS: The measure, which includes ten images used to assess everyday activities in the context of pain-related fear, was administered to 118 subjects with chronic non-specific NP, and proved to be acceptable and feasible. Factor analysis revealed a one-factor solution (which explained 71.12 % of variance). The content of the images was considered adequate, appropriate for the target population, comprehensive, and relevant for evaluating activity-related kinesiophobia. The instrument's internal consistency was good (alpha = 0.954), as was its test-retest stability (ICC 0.979). Construct validity demonstrated a close correlation with the TSK (r = 0.759), and moderate correlations with the PCS (r = 0.583), the NDI (r = 0.520), and a NRS (r = 0.455). CONCLUSION: NeckPix((c)), which was successfully developed following international recommendations, proved to have a good factorial structure and satisfactory psychometric properties. Its use is recommended for research purposes. PMID- 25115921 TI - Epidemiology of partial urorectal septum malformation sequence (or 'persistent cloaca'): a population-based study in seven regions of England and Wales, 1985 2010. AB - BACKGROUND: Partial urorectal septum malformation (pURSM) sequence (or 'persistent cloaca') is a rare congenital anomaly characterised by a joining of the urethral, anal, and genital openings into a single common channel. This study describes the epidemiology of pURSM sequence in England and Wales including prevalence, additional anomalies, and pregnancy outcomes. METHODS: All cases of pURSM sequence prospectively notified to seven congenital anomaly registers in England and Wales during 1985-2010, whether delivered as live births, spontaneous fetal deaths (>=20 weeks' gestation), or elective terminations of pregnancy for fetal anomaly (TOPFA, any gestation), formed this population-based cohort. The risks of spontaneous fetal and infant death were examined by Kaplan-Meier analysis. Differences in prevalence over time, and between regions, were examined by multilevel Poisson regression. RESULTS: 117 cases were recorded among 4,251,241 total births. Six (5%) pregnancies resulted in spontaneous fetal deaths, 53 (45%) in TOPFA, and 58 (50%) in live births. The prevalence was 2.8 (95% CI 2.3 to 3.4) per 100,000 total births, increasing significantly over time (p=0.002) and differing significantly between regions (p=0.005). 77 cases (66%) had at least one additional major congenital anomaly outside the perineum, including 67 (57%) renal, 29 (25%) musculoskeletal, 26 (23%) digestive system, and 24 (21%) cardiovascular anomalies. The risks of spontaneous fetal and infant death were estimated as 8.9% (95% CI 4.1 to 18.8) and 26.3% (95% CI 15.1 to 43.4) respectively. CONCLUSIONS: This is the largest study of the epidemiology of pURSM sequence. The information will be valuable for families and health professionals whenever a case of pURSM sequence is diagnosed. PMID- 25115920 TI - Mesenchymal stromal cell proliferation, gene expression and protein production in human platelet-rich plasma-supplemented media. AB - BACKGROUND: Platelet-rich plasma (PRP) is increasingly used as a cell culture supplement, in order to reduce the contact of human cells with animal-derived products during in vitro expansion. The effect of supplementation changes on cell growth and protein production is not fully characterized. METHODS: Human mesenchymal stromal cells from bone marrow, adipose tissue and Wharton's Jelly were isolated and cultured in PRP-supplemented media. Proliferation, in vitro differentiation, expression of cell surface markers, mRNA expression of key genes and protein secretion were quantified. RESULTS: 10% PRP sustained five to tenfold increased cell proliferation as compared to 10% fetal bovine serum. Regarding cell differentiation, PRP reduced adipogenic differentiation and increased calcium deposits in bone marrow and adipose tissue-mesenchymal stromal cells. Wharton's Jelly derived mesenchymal stromal cells secreted higher concentrations of chemokines and growth factors than other mesenchymal stromal cells when cultured in PRP-supplemented media. Bone marrow derived mesenchymal stromal cells secreted higher concentrations of pro-inflammatory and pro-angiogenic proteins. Mesenchymal stromal cells isolated from adipose tissue secreted higher amounts of extracellular matrix components. CONCLUSIONS: Mesenchymal stromal cells purified from different tissues have distinct properties regarding differentiation, angiogenic, inflammatory and matrix remodeling potential when cultured in PRP supplemented media. These abilities should be further characterized in order to choose the best protocols for their therapeutic use. PMID- 25115924 TI - Senior doctor was present in 87% of anaesthesia cases in 2013. PMID- 25115923 TI - YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression. AB - Whether the Hippo pathway contributes to cell lineage transition under pathological conditions, especially tumorigenesis, remains largely unknown. Here we show that YAP, the major effector of the Hippo pathway, displays a distinct activation pattern in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC); YAP is initially activated by LKB1 loss in lung ADC, which upregulates ZEB2 expression and represses DNp63 transcription in a default manner. During transdifferentiation, YAP is inactivated, which in turn relieves ZEB2-mediated default repression of DNp63 and triggers squamous differentiation reprogramming. Disruption of the YAP barrier for phenotypic transition significantly accelerates squamous transdifferentiation, whereas constitutive YAP activation conversely inhibits this transition. More importantly, ectopic DNp63 expression rescues the inhibitory effect of YAP on squamous transdifferentiation. These findings have established YAP as an essential barrier for lung cancer cell fate conversion and provided a mechanism for regulating cancer plasticity, which might hold important implication for YAP-targeted therapies. PMID- 25115925 TI - Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease. AB - BACKGROUND: The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation. OBJECTIVES: To investigate airway innate immune cellular phenotypes in preterm infants with respiratory distress syndrome (RDS) or CLD. METHODS: Bronchoalveolar lavage (BAL) fluid was obtained from term and preterm infants requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry. RESULTS: Preterm birth was associated with an increase in the proportion of non classical CD14(+)/CD16(+) monocytes on the day of delivery (58.9 +/- 5.8% of total mononuclear cells in preterm vs 33.0 +/- 6.1% in term infants, p = 0.02). Infants with RDS were born with significantly more CD36(+) macrophages compared with the CLD group (70.3 +/- 5.3% in RDS vs 37.6 +/- 8.9% in control, p = 0.02). At day 3, infants born at a low gestational age are more likely to have greater numbers of CD14(+) mononuclear phagocytes in the airway (p = 0.03), but fewer of these cells are functionally polarized as assessed by HLA-DR (p = 0.05) or CD36 (p = 0.05) positivity, suggesting increased recruitment of monocytes or a failure to mature these cells in the lung. CONCLUSIONS: These findings suggest that macrophage polarization may be affected by gestational maturity, that more immature macrophage phenotypes may be associated with the progression of RDS to CLD and that phenotyping mononuclear cells in BAL could predict disease outcome. PMID- 25115927 TI - One-year outcome from an all-comers population of patients with ST-segment elevation myocardial infarction treated with biolimus-eluting stent with biodegradable polymer. AB - OBJECTIVES: To evaluate the performance of biolimus-eluting stent (BES) in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) in a real world clinical scenario. BACKGROUND: Randomized studies suggest that the BES with biodegradable polymer is more effective and safe than early generation coronary stents in patients with STEMI. METHODS: We included all consecutive STEMI patients undergoing PCI in this prospective, multicenter registry. The primary endpoint of the study was the rate of major adverse cardiac events (MACE), a composite of cardiac death, recurrent myocardial infarction and ischemia-driven target vessel revascularization at 1 year follow-up. RESULTS: Between June and December 2012 we enrolled 311 STEMI patients. The primary endpoint occurred in 3.2% (95% confidence interval: 1.6 5.8) of patients: cardiac death, re-infarction, and ischemia-driven TVR occurred in 2.3%, 1.3%, and 0.6% of patients, respectively. One-year MACE-free survival was 96.8% +/- 1.0%. CONCLUSIONS: In a real-world cohort of STEMI patients undergoing PCI, the use of BES is associated with good 1-year clinical outcome. These results confirm and expand previous findings showing the efficacy and safety of BES in the setting of randomized trials. PMID- 25115928 TI - Diaphragmatic hernia caused by heterotopic endometriosis in Chilaiditi syndrome: report of a case. AB - A 50-year-old Japanese female was admitted to our hospital because of ileus due to Chilaiditi syndrome. Her symptoms did not improve with conservative therapy, so chest and abdominal computed tomography (CT) was performed on the fifth day after hospital admission. A diagnosis of incarceration of a right diaphragmatic hernia was established in the coronal view of CT, and emergency surgery was performed. A dilated loop of small intestine was seen in the right thoracic cavity, which was strangulated by the 2-cm defect in the diaphragm. Primary closure of the diaphragm was performed. Approximately 80 cm of the terminal ileum showed obvious ischemic changes, and it was cut and reconstructed. Postoperatively, the patient made an uneventful recovery and was discharged on the 15th postoperative day. A histological examination of the specimen of the diaphragm around the hernia orifice showed the presence of a small cystiform glandular system with hemorrhage and congestion. These findings indicated that heterotopic endometriosis was present in the diaphragm. This report describes the first known case of right diaphragmatic hernia secondary to heterotopic endometriosis in a patient with Chilaiditi syndrome. The clinical course and management of affected patients and a literature review of these three unusual conditions are discussed. PMID- 25115926 TI - Role of the water-metal ion bridge in mediating interactions between quinolones and Escherichia coli topoisomerase IV. AB - Although quinolones have been in clinical use for decades, the mechanism underlying drug activity and resistance has remained elusive. However, recent studies indicate that clinically relevant quinolones interact with Bacillus anthracis (Gram-positive) topoisomerase IV through a critical water-metal ion bridge and that the most common quinolone resistance mutations decrease drug activity by disrupting this bridge. As a first step toward determining whether the water-metal ion bridge is a general mechanism of quinolone-topoisomerase interaction, we characterized drug interactions with wild-type Escherichia coli (Gram-negative) topoisomerase IV and a series of ParC enzymes with mutations (S80L, S80I, S80F, and E84K) in the predicted bridge-anchoring residues. Results strongly suggest that the water-metal ion bridge is essential for quinolone activity against E. coli topoisomerase IV. Although the bridge represents a common and critical mechanism that underlies broad-spectrum quinolone function, it appears to play different roles in B. anthracis and E. coli topoisomerase IV. The water-metal ion bridge is the most important binding contact of clinically relevant quinolones with the Gram-positive enzyme. However, it primarily acts to properly align clinically relevant quinolones with E. coli topoisomerase IV. Finally, even though ciprofloxacin is unable to increase levels of DNA cleavage mediated by several of the Ser80 and Glu84 mutant E. coli enzymes, the drug still retains the ability to inhibit the overall catalytic activity of these topoisomerase IV proteins. Inhibition parallels drug binding, suggesting that the presence of the drug in the active site is sufficient to diminish DNA relaxation rates. PMID- 25115930 TI - Comment on "clinical course and angiographic changes of spontaneous isolated superior mesenteric artery dissection after conservative treatment". PMID- 25115929 TI - Intraoperative dissemination during gastrectomy for gastric cancer associated with serosal invasion. AB - PURPOSE: Free cancer cells shed from the serosal surface of gastric cancer result in peritoneal dissemination. The aim of this study was to clarify the extent of tumor cell implantation due to surgical manipulation during gastrectomy. METHODS: The participants comprised 34 patients who underwent curative gastrectomy for gastric cancer with macroscopic serosal invasion. Two types of cytology were obtained from each patient: (1) cytology from the wound dressing material that covered the serosal invasion area during the operation (Covering Cy), and (2) cytology of the intraperitoneal wash samples (Lavage Cy). RESULT: Thirteen patients showed no serosal invasion histopathologically, and all of these patients had negative results for both Lavage Cy and Covering Cy. Among the 21 patients with histopathologically confirmed serosal invasion, six had positive results for both Lavage Cy and Covering Cy, three showed positive findings for Covering Cy alone, one had positive Lavage Cy alone and 11 patients had negative results for both Lavage Cy and Covering Cy. Disseminated recurrence developed in 10 patients. Seven of the nine patients with positive Covering Cy developed disseminated recurrence, compared to three of 12 patients with negative Covering Cy. Positive Covering Cy findings were significantly associated with disseminated recurrence (p < 0.05). CONCLUSION: We demonstrated that the intraoperative dissemination of gastric cancer can occur during gastrectomy. PMID- 25115933 TI - Spatio-spectral structures in high-order harmonic beams generated with Terawatt 10-fs pulses. AB - A large international effort is nowadays devoted to increase the energy of the extreme ultraviolet pulses by using high-peak power ultrashort fundamental pulses (Terawatt level). Using such fundamental pulses brings specific constraints that need to be addressed. Here we study high-order harmonic generation in gases with 10 fs pulses at Terawatt peak power and demonstrate that extreme ultraviolet beams can be highly structured and complex in various conditions. We use a single shot spatially resolved spectral detection and demonstrate direct observation of the spatio-temporal coupling occurring in the generating medium. Clear and reproducible complex spatio-spectral structures are observed in the far field. Similar structures are reproduced with simulations and we show that they are intimately associated to the high nonlinearity of high-order harmonic generation. Those findings are of prime importance for the generation of high-energy attosecond pulses and reveal important issues for their applications. PMID- 25115934 TI - Coronary artery compression three months after transcatheter pulmonary valve implantation. AB - We report a case of a 29-year-old man who developed exercised-induced myocardial infarction 3 months post Melody valve implantation. We introduce the concept of ruling out dynamic coronary artery compression by simulating transcatheter pulmonary valve implant while increasing cardiac output and thus aortic dimensions in the catheterization laboratory. (c) 2014 Wiley Periodicals, Inc. PMID- 25115932 TI - EEG source connectivity analysis: from dense array recordings to brain networks. AB - The recent past years have seen a noticeable increase of interest for electroencephalography (EEG) to analyze functional connectivity through brain sources reconstructed from scalp signals. Although considerable advances have been done both on the recording and analysis of EEG signals, a number of methodological questions are still open regarding the optimal way to process the data in order to identify brain networks. In this paper, we analyze the impact of three factors that intervene in this processing: i) the number of scalp electrodes, ii) the combination between the algorithm used to solve the EEG inverse problem and the algorithm used to measure the functional connectivity and iii) the frequency bands retained to estimate the functional connectivity among neocortical sources. Using High-Resolution (hr) EEG recordings in healthy volunteers, we evaluated these factors on evoked responses during picture recognition and naming task. The main reason for selection this task is that a solid literature background is available about involved brain networks (ground truth). From this a priori information, we propose a performance criterion based on the number of connections identified in the regions of interest (ROI) that belong to potentially activated networks. Our results show that the three studied factors have a dramatic impact on the final result (the identified network in the source space) as strong discrepancies were evidenced depending on the methods used. They also suggest that the combination of weighted Minimum Norm Estimator (wMNE) and the Phase Synchronization (PS) methods applied on High-Resolution EEG in beta/gamma bands provides the best performance in term of topological distance between the identified network and the expected network in the above-mentioned cognitive task. PMID- 25115935 TI - Acute adiponectin delivery is cardioprotective in the aged female rat heart. AB - AIM: The aged, post-menopausal female heart is characterized by reduced ischemic tolerance, and few therapies currently exist to limit ischemic damage. Adiponectin (APN), a cytokine produced in adipose tissue, limits infarct size and improves functional recovery after ischemia/reperfusion injury in adult hearts. The aim of the present study was to extend these previous studies and determine the cardioprotective efficacy of APN treatment in aged female rats. METHODS: Hearts were isolated from adult (age 6-7 months; n = 10), aged (age 23 months; n = 14) and aged ovariectomized (n = 10) female rats, and subjected to ischemia/reperfusion injury. On ischemia, hearts were infused with 9 MUg of APN or vehicle. Adiponectin receptor 1, adiponectin receptor 2 and adenosine monophosphate-dependent kinase (AMPK) were assessed by western blotting, tumor necrosis factor-alpha and nicotinamide adenine dinucleotide phosphate oxidase levels by real time polymerase chain reaction. Non-reducing western blotting for APN multimers in visceral adipose was also carried out. RESULTS: APN infusion successfully improved post-ischemic left ventricular developed pressure (~10-15%) and attenuated the rise in end diastolic pressure in all groups (P < 0.05). With ischemia/reperfusion injury, phospho-AMPK increased in all groups with additive effects of APN on increasing phospho-AMPK abundance in aged ovary-intact female rats only (P < 0.001). Age-associated increases in pre-ischemic tumor necrosis factor-alpha mRNA were unaffected by APN, whereas nicotinamide adenine dinucleotide phosphate oxidase 2 mRNA levels were attenuated by APN in adult and aged ovariectomized female rats. An age-associated decrease in cardiac adiponectin receptor 2 was observed in conjunction with elevated high molecular weight APN in adipose. CONCLUSIONS: The present data suggest that APN might be a relevant therapy for protecting the aging female heart, albeit through divergent mechanisms that are likely influenced by age-associated estrogen availability. PMID- 25115936 TI - No abnormal hexanucleotide repeat expansion of C9ORF72 in Japanese schizophrenia patients. AB - Abnormal hexanucleotide repeat expansion of C9ORF72 is known to cause neurodegenerative disorders such as frontotemporal dementia. Additionally, patients with psychotic symptoms are more likely to have abnormal hexanucleotide repeat expansion than are patients without them. We investigated the hexanucleotide repeat sizes of C9ORF72 in 466 Japanese schizophrenia patients. We found no abnormal hexanucleotide repeat expansion. In conclusion, C9ORF72 may not be responsible for schizophrenia susceptibility in the Japanese population. PMID- 25115938 TI - Religious pro-sociality? Experimental evidence from a sample of 766 Spaniards. AB - This study explores the relationship between several personal religion-related variables and social behaviour, using three paradigmatic economic games: the dictator (DG), ultimatum (UG), and trust (TG) games. A large carefully designed sample of the urban adult population in Granada (Spain) is employed (N = 766). From participants' decisions in these games we obtain measures of altruism, bargaining behaviour and sense of fairness/equality, trust, and positive reciprocity. Three dimensions of religiosity are examined: (i) religious denomination; (ii) intensity of religiosity, measured by active participation at church services; and (iii) conversion out into a different denomination than the one raised in. The major results are: (i) individuals with "no religion" made decisions closer to rational selfish behaviour in the DG and the UG compared to those who affiliate with a "standard" religious denomination; (ii) among Catholics, intensity of religiosity is the key variable that affects social behaviour insofar as religiously-active individuals are generally more pro-social than non-active ones; and (iii) the religion raised in seems to have no effect on pro-sociality, beyond the effect of the current measures of religiosity. Importantly, behaviour in the TG is not predicted by any of the religion-related variables we analyse. While the results partially support the notion of religious pro-sociality, on the other hand, they also highlight the importance of closely examining the multidimensional nature of both religiosity and pro-social behaviour. PMID- 25115937 TI - Phosphorylation at Y1065 in vinculin mediates actin bundling, cell spreading, and mechanical responses to force. AB - Vinculin is an essential structural adaptor protein that localizes to sites of adhesion and is involved in a number of cell processes including adhesion, spreading, motility, force transduction, and cell survival. The C-terminal vinculin tail domain (Vt) contains the necessary structural components to bind and cross-link actin filaments. Actin binding to Vt induces a conformational change that promotes dimerization through the C-terminal hairpin of Vt and enables actin filament cross-linking. Here we show that Src phosphorylation of Y1065 within the C-terminal hairpin regulates Vt-mediated actin bundling and provide a detailed characterization of Y1065 mutations. Furthermore, we show that phosphorylation at Y1065 plays a role in cell spreading and the response to the application of mechanical force. PMID- 25115941 TI - Alcohol should carry similar warnings to tobacco, MPs say. PMID- 25115940 TI - SMBE Satellite meeting on reticulated microbial evolution 2014--meeting report. PMID- 25115939 TI - Increased risk of dementia in patients exposed to nitrogen dioxide and carbon monoxide: a population-based retrospective cohort study. AB - BACKGROUND: The air pollution caused by vehicular emissions is associated with cognitive decline. However, the associations between the levels of nitrogen dioxide (NO2) and carbon monoxide (CO) exposure and dementia remain poorly defined and have been addressed in only a few previous studies. MATERIALS AND METHODS: In this study, we obtained data on 29547 people from the National Health Insurance Research Database (NHIRD) of Taiwan, including data on 1720 patients diagnosed with dementia between 2000 and 2010, and we evaluated the risk of dementia among four levels of air pollutant. Detailed data on daily air pollution were available from January 1, 1998 to December 31, 2010. Yearly average concentrations of pollutants were calculated from the baseline to the date of dementia occurrence, withdrawal of patients, or the end of the study, and these data were categorized into quartiles, with Q1 being the lowest level and Q4 being the highest. RESULTS: In the case of NO2, the adjusted hazard ratios (HRs) of dementia for all participants in Q2, Q3, and Q4 compared to Q1 were 1.10 (95% confidence interval (CI), 0.96-1.26), 1.01 (95% CI, 0.87-1.17), and 1.54 (95% CI, 1.34-1.77), and in the case of CO, the adjusted HRs were 1.07 (95% CI, 0.92 1.25), 1.37 (95% CI, 1.19-1.58), and 1.61 (95% CI, 1.39-1.85). CONCLUSION: The results of this large retrospective, population-based study indicate that exposure to NO2 and CO is associated with an increased risk of dementia in the Taiwanese population. PMID- 25115942 TI - Achieving solar overall water splitting with hybrid photosystems of photosystem II and artificial photocatalysts. AB - Solar overall water splitting is a promising sustainable approach for solar-to chemical energy conversion, which harnesses solar irradiation to oxidize water to oxygen and reduce the protons to hydrogen. The water oxidation step is vital but difficult to achieve through inorganic photocatalysis. However, nature offers an efficient light-driven water-oxidizing enzyme, photosystem II (PSII). Here we report an overall water splitting natural-artificial hybrid system, in which the plant PSII and inorganic photocatalysts (for example, Ru/SrTiO3:Rh), coupled with an inorganic electron shuttle [Fe(CN)6(3-)/Fe(CN)6(4-)], are integrated and dispersed in aqueous solutions. The activity of this hybrid photosystem reaches to around 2,489 mol H2 (mol PSII)(-1) h(-1) under visible light irradiation, and solar overall water splitting is also achieved under solar irradiation outdoors. The optical imaging shows that the hybrid photosystems are constructed through the self-assembly of PSII adhered onto the inorganic photocatalyst surface. Our work may provide a prototype of natural-artificial hybrids for developing autonomous solar water splitting system. PMID- 25115944 TI - Serial intravascular ultrasound analysis of complex bifurcation coronary lesions treated with the Tryton Bifurcation Stent in conjunction with an everolimus eluting stent: IUVANT (Intravascular Ultrasound Evaluation of Tryton Stent) study. AB - OBJECTIVES: To characterize the treatment of complex bifurcation lesions (BL) with the Tryton Bifurcation Stent (TBS) paired with an everolimus-eluting stent (EES). BACKGROUND: Complex BL are associated with higher procedural complications and poorer long-term outcomes. The TBS is a dedicated side-branch (SB) stent designed to be used in conjunction with a standard drug-eluting stent. METHODS: Prospectively identified, consecutive patients underwent TBS+EES stenting of BL using a protocol which included TBS postdilation and simultaneous final kissing balloon inflations (FKBI). All lesions were systematically evaluated with coronary angiography and IVUS, obtained at procedure completion and at 9 months, and were assessed by independent core laboratories. RESULTS: Thirty-three BL were treated in 32 patients presenting primarily (87.5%) with stable angina and complex BL with angiographic apparent disease in the main vessel (MV) and SB in 87.9% and 75% by site and core evaluation, respectively. Procedural success was 100% and high postprocedure percent stent expansion (MV 96 [93, 109]%, SB 88 [77, 100]%, carina MV 135 [99, 166]%, carina SB 116 [91, 130]%) was demonstrated by IVUS. At 9-month angiographic follow-up (n = 28 patients), one MV in-segment restenosis and one SB in-stent restenosis were observed. SB in-stent late lumen loss was 0.41 +/- 0.27 mm. IVUS assessment revealed the absence of stent recoil; percent carinal neointimal hyperplasia (NIH) was 1.8 [0.0,11.2]% in MV and 15.0 [6.7,23.5]% in SB, with NIH volume obstruction of 2.0 [0.7,4.3]% in MV and 14.2 [7.5,29.6]% in SB. CONCLUSIONS: Stenting of complex BL with the TBS+EES provides high acute success with sustained clinical, angiographic, and IVUS results at 9 months. These excellent results are likely due to the extent of stent expansion at the carina. PMID- 25115946 TI - Complete genome sequence of virulent bacteriophage SHOU24, which infects foodborne pathogenic Vibrio parahaemolyticus. AB - A novel lytic Vibrio parahaemolyticus phage (SHOU24) belonging to the family Siphoviridae was isolated from aquatic market sewage. The phage is only able to infect V. parahaemolyticus containing a tdh gene. SHOU24 has a linear genome of 77,837 bp with a G+C content of 46.0 %. In total, 88 predicted proteins have homologues in databases, and the majority of the core genes share high sequence similarity with genes from unrelated viruses and bacteria. Genes related to lysogeny and host lysis were not detected. However, the detection method, the results of a one-step growth experiment and analysis using the Phage Classification Tool Set (PHACTS) indicate that SHOU24 is lytic. A bioinformatics analysis showed that SHOU24 is not closely related to other Vibrio phages. PMID- 25115943 TI - Complex communities of small protists and unexpected occurrence of typical marine lineages in shallow freshwater systems. AB - Although inland water bodies are more heterogeneous and sensitive to environmental variation than oceans, the diversity of small protists in these ecosystems is much less well known. Some molecular surveys of lakes exist, but little information is available from smaller, shallower and often ephemeral freshwater systems, despite their global distribution and ecological importance. We carried out a comparative study based on massive pyrosequencing of amplified 18S rRNA gene fragments of protists in the 0.2-5 MUm size range in one brook and four shallow ponds located in the Natural Regional Park of the Chevreuse Valley, France. Our study revealed a wide diversity of small protists, with 812 stringently defined operational taxonomic units (OTUs) belonging to the recognized eukaryotic supergroups (SAR--Stramenopiles, Alveolata, Rhizaria- Archaeplastida, Excavata, Amoebozoa, Opisthokonta) and to groups of unresolved phylogenetic position (Cryptophyta, Haptophyta, Centrohelida, Katablepharida, Telonemida, Apusozoa). Some OTUs represented deep-branching lineages (Cryptomycota, Aphelida, Colpodellida, Tremulida, clade-10 Cercozoa, HAP-1 Haptophyta). We identified several lineages previously thought to be marine including, in addition to MAST-2 and MAST-12, already detected in freshwater, MAST-3 and possibly MAST-6. Protist community structures were different in the five ecosystems. These differences did not correlate with geographical distances, but seemed to be influenced by environmental parameters. PMID- 25115948 TI - An evaluation of e-prescribing at a national level. AB - OBJECTIVE: The aim of the article is to describe the process of implementing the Estonian national second generation electronic prescription service (e prescription) and determine if the objectives set by the Estonian government were fulfilled. MATERIALS AND METHODS: The study presents an analysis of both retrospective and current data in the evaluation phase of a design research project. Sources include, among others, publicly available documents and previous evaluation studies. RESULTS: According to all of the major stakeholders, the Estonian e-prescription service has very high usability and user satisfaction scores have been high. There is only little empirical evidence available to confirm if the benefits aimed for in the creation of the service were achieved. From a public administration viewpoint, the implementation of e-prescription has led to potential efficiency gains. CONCLUSION: The Estonian second-generation e prescription system is widely used by citizens, healthcare providers and administrators alike. However, there are gaps in measuring the impact of the service, especially with respect to time savings and enhanced healthcare quality. Additional functionalities will be key drivers in creating benefits for all stakeholders. Future nationwide e-health services should have a more rigorous evaluation process carried out during the design and implementation stages. PMID- 25115947 TI - Socioeconomic Adversity and Women's Sleep: Stress and Chaos as Mediators. AB - We examined income-to-needs ratio, perceived economic well-being, and education and their relations with European and African American women's sleep (n = 219). Sleep was examined through actigraphy and self-reports. Income-to-needs ratio was related to sleep minutes. Perceived economic well-being and education were associated with subjective sleep problems. Perceived stress mediated relations between both income-to-needs ratio and economic well-being and subjective sleep problems. Chaos emerged as a mediator linking income-to-needs ratio and subjective sleep problems. African American women had fewer sleep minutes and lower sleep efficiency than European Americans, and more robust relations between economic well-being and stress was observed for European Americans. Findings highlight the importance of economic adversity for women's sleep and explicate some pathways of risk. PMID- 25115949 TI - Saliva viscosity as a potential risk factor for oral malodor. AB - OBJECTIVES: The objective of this study was to assess whether saliva viscosity, measured by a viscometer, was a predictor of oral malodor. MATERIALS AND METHODS: The subjects were 617 patients who visited an oral malodor clinic. The organoleptic test (OT) was used for diagnosis of oral malodor. An oral examination assessed the numbers of teeth present and decayed teeth as well as the presence or absence of dentures. Further, periodontal pocket depths (PD), gingival bleeding, dental plaque and tongue coating were investigated. Unstimulated saliva were collected for 5 min. Saliva viscosity was measured with a viscometer. Logistic regression analysis with oral malodor status by OT as a dependent variable was performed. Possible confounders including age, gender, number of teeth present, number of decayed teeth, number of teeth with PD >= 4 mm, number of teeth with bleeding on probing, presence or absence of dentures, plaque index, area of tongue coating, saliva flow rate, saliva pH and saliva viscosity were used as independent variables. RESULTS: Saliva viscosity (p = 0.047) along with the number of teeth with PD >=4 mm (p = 0.001), plaque index (p = 0.037) and area of tongue coating (p < 0.001) were significant variables for oral malodor. Subjects with a higher number of teeth with PD >= 4 mm (OR = 1.32), plaque index (OR = 2.13), area of tongue coating (OR = 3.17) and saliva viscosity (OR = 1.10) were more likely to have oral malodor compared to those with lower values. CONCLUSIONS: The results suggested that high saliva viscosity could be a potential risk factor for oral malodor. PMID- 25115950 TI - An assessment of the usefulness of Kinesiograph as an aid in the diagnosis of TMD: a review of Manfredini et al.'s studies. AB - AIM: Performing a literature review of publications by Dr. Manfredini et al. related to their temporomandibular joint (TMJ) injection therapy outcome with conclusions on the clinical utility of computerized measurement devices used in the management of temporomandibular disorders (TMDs). In addition, reviewing their published opinion on an occlusion: TMD versus a biopsychosocial paradigm for TMD. Manfredini et al. authored an article published in the Journal of the American Dental Association (JADA) 2013, "An Assessment of the usefulness of jaw kinesiography in monitoring temporomandibular disorders," the most recent of 12 articles. In all studies, subjects received TMJ injections with an objective measurement outcome criterion; increased maximum mouth opening (MMO) and subjective symptom improvement of pain and chewing function. In the 2013 JADA article, the Mandibular Kinesiograph, referred to as KG, measured MMO before and after therapy. In 11 prior articles, all subject groups with limited mouth opening exhibited very significant increased MMO post-treatment, documenting treatment success using the same 2013 protocol. The 2013 study showed a 1.1 mm improved MMO, described as insignificant. The authors did not critique or explain the aberrant, skewed 2013 outcome data contrasted with their prior studies, which showed overwhelmingly significant increased MMO. Instead, they concluded that the MMO recording device was clinically useless. This motivated a literature review of the authors' TMD publications. CONCLUSION: The publications by Manfredini et al. recognized proponents of the psychosocial model of TMD, including the 2013 article, appear to be part of a campaign denying an occlusion: TMD relationship and disparaging the specific computerized measurement devices and the dentists using them in the management of their TMD patients using neuromuscular occlusion dental treatment. PMID- 25115951 TI - Thermodynamic consistencies and anomalies among end-member silicate garnets. AB - Materials with the garnet crystal structure include silicate minerals of importance both in geology, on account of their use in geothermobarometry, and industrially as abrasives. As a consequence of the former, there is considerable published thermodynamic information concerning them. We here examine this thermodynamic information for end-member silicate garnets (some of which are synthetic since not all occur in nature) for consistencies and anomalies, using thermodynamic relations between thermodynamic properties that we have established over recent years. The principal properties of interest are formula volume, heat capacity, entropy, formation enthalpy (from which the Gibbs energy may be obtained), and isothermal compressibility. A significant observation is that the ambient-temperature heat capacities of the silicate garnets are rather similar, whereas their ambient-temperature entropies are roughly proportional to their formula volumes. Evaluation of their Debye temperatures implies that their vibrational contributions to heat capacity are fully excited at ambient temperatures. The relatively small isothermal compressibilities of these garnets is related to the rigidity of their constituent silicate tetrahedra. We here establish additive single-ion values for each of the thermodynamic properties, which may be applied in estimating corresponding values for related materials. PMID- 25115952 TI - The stigmatisation of abortion: a qualitative analysis of print media in Great Britain in 2010. AB - The media play a significant part in shaping public perceptions of health issues, and abortion attracts continued media interest. Detailed examination of media constructions of abortion may help to identify emerging public discourse. Qualitative content analysis was used to examine if and how the print media in contributes to the stigmatisation of abortion. Articles from seven British and five Scottish national newspapers from 2010 were analysed for overall framings of abortion and emergent themes, including potentially stigmatising discursive constructs and language. Abortion was found to be presented using predominantly negative language and discursive associations as 'risky', and in association with other 'discredited' social practices. Key perspectives were found to be absent or marginalised, including those of women who have sought abortion. Few articles framed abortion as a positive and legitimate choice. Negative media representations of abortion contribute to the stigmatisation of the procedure and of women who have it, and reflect a discrediting of women's reproductive decision making. There is a need to challenge the notion that abortion stigma is inevitable, and to encourage positive framings of abortion in the media and other public discourse. PMID- 25115953 TI - Clonal structure, seed set, and self-pollination rate in mass-flowering bamboo species during off-year flowering events. AB - Bamboos are typical examples of highly synchronized semelparous species. Their mass-flowering events occur at supra-annual intervals but they sometimes flower on a small scale in off-years. If some bamboo ramets (culms) of a genet flower and die in off-years, whereas other culms of the same genet do not flower synchronously, the genet can still survive blooming in an off-year and could participate in the next mass-flowering event. At genet level, the effect might be similar to that achieved by synchronously reproducing iteroparous plants. In addition, if multiple genets flower simultaneously in off-years, cross pollination will be promoted. However, it is not known whether all the culms in a genet flower synchronously and whether multiple genets flower in off-years. We determined the clonal structure of three temperate dwarf bamboo species, i.e., Sasa senanensis, S. kurilensis, and S. palmata, at 24 off-year flowering sites and the surrounding areas in northern Japan using seven microsatellite markers. We also estimated seed set at seven of the sites and self-pollination rates at five sites to determine off-year reproductive success. Next, we investigated whether seed sets at the culm level were related to flowering area and/or number of flowering genets, using generalized linear mixed-effect models (GLMMs). Multiple genets flowered at 9/24 flowering sites. We found that 40/96 of the genets identified had some flowering culms. Non-flowering culms were present in 24/40 flowering genets. Seed set was in the range 2.2%-12.5% and the self pollination rate was 96.3%. In the best GLMM, seed set increased with flowering area. Seeds were produced in off-years, but cross-pollination was rare in off years. We suggest that some dwarf bamboos may exhibit iteroparity or imperfectly synchronized semelparity at the genet level, a characteristic similar to that of other reproductively synchronous plants. We also found synchronous flowering of a few genets even in off-years. PMID- 25115957 TI - Retrospective non-uniform illumination correction techniques in images of tuberculosis. AB - Image pre-processing is highly significant in automated analysis of microscopy images. In this work, non-uniform illumination correction has been attempted using the surface fitting method (SFM), multiple regression method (MRM), and bidirectional empirical mode decomposition (BEMD) in digital microscopy images of tuberculosis (TB). The sputum smear positive and negative images recorded under a standard image acquisition protocol were subjected to illumination correction techniques and evaluated by error and statistical measures. Results show that SFM performs more efficiently than MRM or BEMD. The SFM produced sharp images of TB bacilli with better contrast. To further validate the results, multifractal analysis was performed that showed distinct variation before and after implementation of illumination correction by SFM. Results demonstrate that after illumination correction, there is a 26% increase in the number of bacilli, which aids in classification of the TB images into positive and negative, as TB positivity depends on the count of bacilli. PMID- 25115958 TI - Energy transport and coherence properties of acoustic phonons generated by optical excitation of a quantum dot. AB - The energy transport of acoustic phonons generated by the optical excitation of a quantum dot as well as the coherence properties of these phonons are studied theoretically both for the case of a pulsed excitation and for a continuous wave (CW) excitation switched on instantaneously. For a pulsed excitation, depending on pulse area and pulse duration, a finite number of phonon wave packets is emitted, while for the case of a CW excitation a sequence of wave packets with decreasing amplitude is generated after the excitation has been switched on. We show that the energy flow associated with the generated phonons is partly related to coherent phonon oscillations and partly to incoherent phonon emission. The efficiency of the energy transfer to the phonons and the details of the energy flow depend strongly and in a non-monotonic way on the Rabi frequency exhibiting a resonance behavior. However, in the case of CW excitation it turns out that the total energy transferred to the phonons is directly linked in a monotonic way to the Rabi frequency. PMID- 25115960 TI - [Anterior resection syndrome and quality of life in rectal cancer patients]. PMID- 25115959 TI - [Femoroacetabular impingement in athletes: pathology, diagnostics and operative therapy options]. AB - Femoroacetabular impingement (FAI) and its therapy has gained importance in the last decade and several studies could show that if untreated it may lead to osteoarthritis of the hip joint. In this article an overview of the pathology of FAI, the diagnosis and treatment options are presented. A closer look is taken at the treatment of elite athletes regarding the different techniques. The first own clinical and radiological results of 91 patients treated by the arthroscopically assisted anterior mini-open approach are presented with very good results and significant postoperative improvement regarding the hip injury and osteoarthritis outcome score (HOOS), the Western Ontario and McMasters University (WOMAC) osteoarthritis index and the University of California Los Angeles (UCLA) activity score, as well as alpha angle correction. This technique which is poorly represented in the literature can be used as a treatment option for FAI. The rehabilitation program is comparable to hip arthroscopy. PMID- 25115961 TI - Evolution of external genitalia: insights from reptilian development. AB - External genitalia are found in each of the major clades of amniotes. The phallus is an intromittent organ that functions to deliver sperm into the female reproductive tract for internal fertilization. The cellular and molecular genetic mechanisms of external genital development have begun to be elucidated from studies of the mouse genital tubercle, an embryonic appendage adjacent to the cloaca that is the precursor of the penis and clitoris. Progress in this area has improved our understanding of genitourinary malformations, which are among the most common birth defects in humans, and created new opportunities for comparative studies of other taxa. External genitalia evolve rapidly, which has led to a striking diversity of anatomical forms. Within the past year, studies of external genital development in non-mammalian amniotes, including birds, lizards, snakes, alligators, and turtles, have begun to shed light on the molecular and morphogenetic mechanisms underlying the diversification of phallus morphology. Here, we review recent progress in the comparative developmental biology of external genitalia and discuss the implications of this work for understanding external genital evolution. We address the question of the deep homology (shared common ancestry) of genital structures and of developmental mechanisms, and identify new areas of investigation that can be pursued by taking a comparative approach to studying development of the external genitalia. We propose an evolutionary interpretation of hypospadias, a congenital malformation of the urethra, and discuss how investigations of non-mammalian species can provide novel perspectives on human pathologies. PMID- 25115963 TI - Biocatalytic coatings for air pollution control: a proof of concept study on VOC biodegradation. AB - Although biofilm-based biotechnologies exhibit a large potential as solutions for off-gas treatment, the high water content of biofilms often causes pollutant mass transfer limitations, which ultimately limit their widespread application. The present study reports on the proof of concept of the applicability of bioactive latex coatings for air pollution control. Toluene vapors served as a model volatile organic compound (VOC). The results showed that Pseudomonas putida F1 cells could be successfully entrapped in nanoporous latex coatings while preserving their toluene degradation activity. Bioactive latex coatings exhibited toluene specific biodegradation rates 10 times higher than agarose-based biofilms, because the thin coatings were less subject to diffusional mass transfer limitations. Drying and pollutant starvation were identified as key factors inducing a gradual deterioration of the biodegradation capacity in these innovative coatings. This study constitutes the first application of bioactive latex coatings for VOC abatement. These coatings could become promising means for air pollution control. PMID- 25115962 TI - Failed stabilization for long-term potentiation in the auditory cortex of FMR1 knockout mice. AB - Fragile X syndrome is a developmental disorder that affects sensory systems. A null mutation of the Fragile X Mental Retardation protein 1 (Fmr1) gene in mice has varied effects on developmental plasticity in different sensory systems, including normal barrel cortical plasticity, altered ocular dominance plasticity and grossly impaired auditory frequency map plasticity. The mutation also has different effects on long-term synaptic plasticity in somatosensory and visual cortical neurons, providing insights on how it may differentially affect the sensory systems. Here we present evidence that long-term potentiation (LTP) is impaired in the developing auditory cortex of the Fmr1 knockout (KO) mice. This impairment of synaptic plasticity is consistent with impaired frequency map plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role of LTP in sensory map plasticity during early sensory development. PMID- 25115964 TI - Revealing the dark side of a bright exciton-polariton condensate. AB - Condensation of bosons causes spectacular phenomena such as superfluidity or superconductivity. Understanding the nature of the condensed particles is crucial for active control of such quantum phases. Fascinating possibilities emerge from condensates of light-matter-coupled excitations, such as exciton-polaritons, photons hybridized with hydrogen-like bound electron-hole pairs. So far, only the photon component has been resolved, while even the mere existence of excitons in the condensed regime has been challenged. Here we trace the matter component of polariton condensates by monitoring intra-excitonic terahertz transitions. We study how a reservoir of optically dark excitons forms and feeds the degenerate state. Unlike atomic gases, the atom-like transition in excitons is dramatically renormalized on macroscopic ground state population. Our results establish fundamental differences between polariton condensation and photon lasing and open possibilities for coherent control of condensates. PMID- 25115965 TI - Learning a weighted meta-sample based parameter free sparse representation classification for microarray data. AB - Sparse representation classification (SRC) is one of the most promising classification methods for supervised learning. This method can effectively exploit discriminating information by introducing a [Symbol: see text]1 regularization terms to the data. With the desirable property of sparisty, SRC is robust to both noise and outliers. In this study, we propose a weighted meta sample based non-parametric sparse representation classification method for the accurate identification of tumor subtype. The proposed method includes three steps. First, we extract the weighted meta-samples for each sub class from raw data, and the rationality of the weighting strategy is proven mathematically. Second, sparse representation coefficients can be obtained by [Symnbol: see text]1 regularization of underdetermined linear equations. Thus, data dependent sparsity can be adaptively tuned. A simple characteristic function is eventually utilized to achieve classification. Asymptotic time complexity analysis is applied to our method. Compared with some state-of-the-art classifiers, the proposed method has lower time complexity and more flexibility. Experiments on eight samples of publicly available gene expression profile data show the effectiveness of the proposed method. PMID- 25115967 TI - Automating lexical cross-mapping of ICNP to SNOMED CT. AB - OBJECTIVES: The purpose of this study was to examine the feasibility of automating lexical cross-mapping of a logic-based nursing terminology (ICNP) to SNOMED CT using the Unified Medical Language System (UMLS) maintained by the U.S. National Library of Medicine. METHODS: A two-stage approach included patterns identification, and application and evaluation of an automated term matching procedure. The performance of the automated procedure was evaluated using a test set against a gold standard (i.e. concept equivalency table) created independently by terminology experts. RESULTS: There were lexical similarities between ICNP diagnostic concepts and SNOMED CT. The automated term matching procedure was reliable as presented in recall of 65%, precision of 79%, accuracy of 82%, F-measure of 0.71 and the area under the receiver operating characteristics (ROC) curve of 0.78 (95% CI 0.73-0.83). When the automated procedure was not able to retrieve lexically matched concepts, it was also unlikely for terminology experts to identify a matched SNOMED CT concept. CONCLUSIONS: Although further research is warranted to enhance the automated matching procedure, the combination of cross-maps from UMLS and the automated procedure is useful to generate candidate mappings and thus, assist ongoing maintenance of mappings which is a significant burden to terminology developers. PMID- 25115966 TI - Sex-based differences in bleeding and long term adverse events after percutaneous coronary intervention for acute myocardial infarction: three year results from the HORIZONS-AMI trial. AB - BACKGROUND: Studies have shown sex-based disparities in ST-segment elevation myocardial infarction (STEMI) management and prognosis. We sought to compare women and men undergoing primary percutaneous coronary intervention (PCI) for STEMI in a large, prospective, contemporary context. METHODS: The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial randomized 3,602 patients (23.4% women and 76.6% men) with STEMI presenting within 12 hr of onset of symptoms to bivalirudin or heparin plus glycoprotein IIb/IIIa inhibitors and to PCI with drug-eluting or bare metal stents. RESULTS: Compared with men, women presented later after symptom onset and were more often treated with medical management alone (6.9% vs. 4.7%; P = 0.01). Women had significantly higher rates of 3-year major adverse cardiac events (MACE) and major bleeding. After adjusting for baseline differences, female sex remained an independent predictor of major bleeding (hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.41-2.33; P < 0.0001) but not of MACE (HR 1.09; 95% CI 0.91-1.32; P = 0.35). CONCLUSIONS: This study found that women with STEMI are at increased risk of bleeding as compared to men. While female sex may not directly contribute to increased risk of MACE, it is, however, associated with the presence of comorbidities that increase the risk of ischemic events long-term. Further dedicated studies are needed to confirm these findings and to assess strategies to optimize both the initial emergent treatment and long-term management in this high-risk subset. (c) 2014 Wiley Periodicals, Inc. PMID- 25115968 TI - The global regulator FfSge1 is required for expression of secondary metabolite gene clusters but not for pathogenicity in Fusarium fujikuroi. AB - The plant pathogenic fungus Fusarium fujikuroi is the causal agent of bakanae disease on rice due to its ability to produce gibberellins. Besides these phytohormones, F. fujikuroi is able to produce several other secondary metabolites (SMs). Although much progress has been made in the field of secondary metabolism, the transcriptional regulation of SM biosynthesis is complex and still incompletely understood. Environmental conditions, global as well as pathway-specific regulators and chromatin remodelling have been shown to play major roles. Here, the role of FfSge1, a homologue of the morphological switch regulators Wor1 and Ryp1 in Candida albicans and Histoplasma capsulatum, respectively, is explored with emphasis on secondary metabolism. FfSge1 is not required for formation of conidia and pathogenicity but is involved in vegetative growth. Transcriptome analysis of the mutant Deltaffsge1 compared with the wild type, as well as comparative chemical analysis between the wild type, Deltaffsge1 and OE:FfSGE1, revealed that FfSge1 functions as a global activator of secondary metabolism in F. fujikuroi. Double mutants of FfSGE1 and other SM regulatory genes brought insights into the hierarchical regulation of secondary metabolism. In addition, FfSge1 is also required for expression of a yet uncharacterized SM gene cluster containing a non-canonical non-ribosomal peptide synthetase. PMID- 25115971 TI - Erratum to: Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid. PMID- 25115969 TI - What Role Does Sleep Play in Weight Gain in the First Semester of University? AB - We hypothesized that shorter sleep durations and greater variability in sleep patterns are associated with weight gain in the first semester of university. Students (N = 132) completed daily sleep diaries for 9 weeks, completed the MEQ (chronotype) and CES-D (depressed mood) at week 9, and self-reported weight/height (weeks 1 & 9). Mean and variability scores were calculated for sleep duration (TST, TSTv), bedtime (BT, BTv), and wake time (WT, WTv). An initial hierarchical regression evaluated (block 1) sex, ethnicity; (block 2) depressed mood, chronotype; (block 3) TST; (block 4) BT, WT; and (block 5; R(2) change = 0.09, p = 0.005) TSTv, BTv, WTv with weight change. A sex-by-TSTv interaction was found. A final model showed that ethnicity, TST, TSTv, and BTv accounted for 31% of the variance in weight change for males; TSTv was the most significant contributor (R(2) change = 0.21, p < 0.001). Daily variability in sleep duration contributes to males' weight gain. Further investigation needs to examine sex-specific outcomes for sleep and weight. PMID- 25115970 TI - A numerical investigation of the electric and thermal cell kill distributions in electroporation-based therapies in tissue. AB - Electroporation-based therapies are powerful biotechnological tools for enhancing the delivery of exogeneous agents or killing tissue with pulsed electric fields (PEFs). Electrochemotherapy (ECT) and gene therapy based on gene electrotransfer (EGT) both use reversible electroporation to deliver chemotherapeutics or plasmid DNA into cells, respectively. In both ECT and EGT, the goal is to permeabilize the cell membrane while maintaining high cell viability in order to facilitate drug or gene transport into the cell cytoplasm and induce a therapeutic response. Irreversible electroporation (IRE) results in cell kill due to exposure to PEFs without drugs and is under clinical evaluation for treating otherwise unresectable tumors. These PEF therapies rely mainly on the electric field distributions and do not require changes in tissue temperature for their effectiveness. However, in immediate vicinity of the electrodes the treatment may results in cell kill due to thermal damage because of the inhomogeneous electric field distribution and high current density during the electroporation-based therapies. Therefore, the main objective of this numerical study is to evaluate the influence of pulse number and electrical conductivity in the predicted cell kill zone due to irreversible electroporation and thermal damage. Specifically, we simulated a typical IRE protocol that employs ninety 100-us PEFs. Our results confirm that it is possible to achieve predominant cell kill due to electroporation if the PEF parameters are chosen carefully. However, if either the pulse number and/or the tissue conductivity are too high, there is also potential to achieve cell kill due to thermal damage in the immediate vicinity of the electrodes. Therefore, it is critical for physicians to be mindful of placement of electrodes with respect to critical tissue structures and treatment parameters in order to maintain the non-thermal benefits of electroporation and prevent unnecessary damage to surrounding healthy tissue, critical vascular structures, and/or adjacent organs. PMID- 25115972 TI - A clinical experience of 'STAMP' plate-guided Bonebridge implantation. AB - CONCLUSION: The surface template-assisted marker positioning (STAMP) method is useful for successful BonebridgeTM (BB) implantation on a planned site while avoiding dangerous positions. OBJECTIVES: To confirm the usefulness of the STAMP method for the safe operation of BB. METHODS: From a patient's temporal bone CT data, a guide plate and confirmation plate were generated by the STAMP method. The guide plate is used to mark the correct place for implantation, while the confirmation plate lets us know the correct angle and depth of the hole. RESULTS: With the guide plate, the correct place for BB implantation was easily found. The hole was made to be an appropriate size with the confirmation plate while exposing only a small part of sigmoid sinus as simulated. Finally, the BB implant was successfully placed exactly at the planned site. PMID- 25115973 TI - Recent development of sandwich assay based on the nanobiotechnologies for proteins, nucleic acids, small molecules, and ions. PMID- 25115975 TI - Unhelpful information about adverse drug reactions. PMID- 25115976 TI - Roughness and morphology of composites: influence of type of material, fluoride solution, and time. AB - This study evaluated the effect of fluoride solutions on surface roughness and morphology of composites in the short and long term. Specimens were randomly assigned to experimental groups (n=5) according to type of composite (nanofilled, microhybrid, microfilled) and immersion media (artificial saliva, 0.05% sodium fluoride solution, Fluordent Reach, Oral-B, and Fluorgard). Roughness was evaluated at time intervals: T 0 after 24 h in artificial saliva (baseline); T 60 after being in assigned immersion media for 1 min daily over 60 days; and T final after artificial aging (20,000 thermal cycles, 1,200,000 mechanical loading cycles, and continuous immersion for 1,825 min). Surface morphology was qualitatively analyzed by scanning electron microscopy (SEM) at T 60 and T final. Roughness data were submitted to analysis of variance for mixed repeated measures, Sidak, and Tukey tests at alpha=0.05. Micro-filled resin showed the highest roughness values. Fluoride solutions had no influence on roughness. Higher roughness values were observed after artificial aging. In SEM observations after the artificial aging, the specimens showed surface degradation, irrespective of immersion medium or type of composite. Nano-filled resin showed higher loss of resin matrix and protrusion of filler particles. Roughness was not influenced by fluoride solutions; however, it is material dependent and increases over time. PMID- 25115977 TI - A reversible conversion between a skyrmion and a domain-wall pair in a junction geometry. AB - Skyrmions are expected to be a key component of the next-generation of spintronics: known as 'skyrmionics'. On the other hand, there is a well established memory device encoded by a sequence of domain walls. Here we show a conversion is possible between a skyrmion and a domain-wall pair by connecting wide and narrow nanowires, enabling the information transmission between a skyrmion device and a domain-wall device. Our results will be the basis of a hybrid device made of skyrmions and domain walls, where the encoded information in domain walls is converted into skyrmions, and then read out by converting the skyrmions back to domain walls after a functional control of the skyrmions. Such a device has the potential to outperform domain-wall racetrack memory because of the combined advantages of domain walls and skyrmions for spintronics application. PMID- 25115979 TI - Chronic fibrosing osteomyelitis: a position statement. AB - Chronic Fibrosing Osteomyletis (CFO) is a commonly found condition which is often undiagnosed because of its co-morbidities with other systemic conditions. Clinicians should consider CFO in their differential diagnosis when confronted with complex head, neck and facial pain patients who present with multi symptom/systems overlay. A multi-disciplinary approach is often required for proper patient diagnosis and treatment. PMID- 25115978 TI - The Swiss Systemic lupus erythematosus Cohort Study (SSCS) - cross-sectional analysis of clinical characteristics and treatments across different medical disciplines in Switzerland. AB - OBJECTIVES: To describe disease characteristics and treatment modalities in a multidisciplinary cohort of systemic lupus erythematosus (SLE) patients in Switzerland. METHODS: Cross-sectional analysis of 255 patients included in the Swiss SLE Cohort and coming from centres specialised in Clinical Immunology, Internal Medicine, Nephrology and Rheumatology. Clinical data were collected with a standardised form. Disease activity was assessed using the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA SLEDAI), an integer physician's global assessment score (PGA) ranging from 0 (inactive) to 3 (very active disease) and the erythrocyte sedimentation rate (ESR). The relationship between SLE treatment and activity was assessed by propensity score methods using a mixed-effect logistic regression with a random effect on the contributing centre. RESULTS: Of the 255 patients, 82% were women and 82% were of European ancestry. The mean age at enrolment was 44.8 years and the median SLE duration was 5.2 years. Patients from Rheumatology had a significantly later disease onset. Renal disease was reported in 44% of patients. PGA showed active disease in 49% of patients, median SLEDAI was 4 and median ESR was 14 millimetre/first hour. Prescription rates of anti-malarial drugs ranged from 3% by nephrologists to 76% by rheumatologists. Patients regularly using anti malarial drugs had significantly lower SELENA-SLEDAI scores and ESR values. CONCLUSION: In our cohort, patients in Rheumatology had a significantly later SLE onset than those in Nephrology. Anti-malarial drugs were mostly prescribed by rheumatologists and internists and less frequently by nephrologists, and appeared to be associated with less active SLE. PMID- 25115980 TI - Differentiation in the microbial ecology and activity of suspended and attached bacteria in a nitritation-anammox process. AB - A directed differentiation between the biofilm and suspension was observed in the molecular microbial ecology and gene expression of different bacteria in a biofilm nitritation-anammox process operated at varying hydraulic residence times (HRT) and nitrogen loading rates (NLR). The highest degree of enrichment observed in the biofilm was of anaerobic ammonia-oxidizing bacteria (AMX) followed by that of Nitrospira spp. related nitrite-oxidizing bacteria (NOB). For AMX, a major shift from Candidatus "Brocadia fulgida" to Candidatus "Kuenenia stuttgartiensis" in both suspension and biofilm was observed with progressively shorter HRT, using discriminatory biomarkers targeting the hydrazine synthase (hzsA) gene. In parallel, expression of the hydrazine oxidoreductase gene (hzo), a functional biomarker for AMX energy metabolism, became progressively prominent in the biofilm. A marginal but statistically significant enrichment in the biofilm was observed for Nitrosomonas europaea related ammonia-oxidizing bacteria (AOB). In direct contrast to AMX, the gene expression of ammonia monooxygenase subunit A (amoA), a functional biomarker for AOB energy metabolism, progressively increased in suspension. Using gene expression and biomass concentration measures in conjunction, it was determined that signatures of AOB metabolism were primarily present in the biofilm throughout the study. On the other hand, AMX metabolism gradually shifted from being uniformly distributed in both the biofilm and suspension to primarily the biofilm at shorter HRTs and higher NLRs. These results therefore highlight the complexity and key differences in the microbial ecology, gene expression and activity between the biofilm and suspension of a nitritation-anammox process and the biokinetic and metabolic drivers for such niche segregation. PMID- 25115981 TI - [Uncommon clinical manifestations of cutaneous leishmaniasis]. AB - Cutaneous leishmaniasis is one of the most common dermatoses of the tropics. A major focus of this disease is the Syrian city of Aleppo, after which it was named in many textbooks ("Aleppo boil"). The first cases of cutaneous leishmaniasis were reported from Aleppo particularly more than 100 years ago. Syria is one of the most affected countries worldwide. This disease used to be well documented until the onset of the war in Syria in 2012, which is also supported by the numbers of the World Health Organisation (WHO), and Aleppo used to be the most affected Syrian city. Since 2012, the documentation of cutaneous leishmaniasis in Syria is no longer possible. An outbreak of cutaneous leishmaniasis has been detected especially in the besieged regions due to missing prevention measures against the sandflies and a lack of medical care. A short summary of the epidemiologic situation in Syria as well as outstanding and uncommon clinical manifestations of cutaneous leishmaniasis in Aleppo are presented. PMID- 25115982 TI - [Comedo or basal cell carcinoma?]. PMID- 25115987 TI - 57Fe Mossbauer studies across the spin density wave transition in BaFe2-xRuxAs2. AB - Mossbauer measurements have been carried out in powdered single crystalline samples of BaFe(2-x)RuxAs(2), for Ru concentration in the x = 0.0-0.5 range. The internal hyperfine field (B(hf)) measured at 5 K is found to decrease with an increase in Ru concentration, consistent with the disappearance of a magnetic ground state with Ru substitution. The temperature dependent Mossbauer measurements have been used to study the evolution of magnetic ordering at the Fe sites, in samples with a Ru fraction of x = 0.1 and 0.5. From the analysis of the data, it is surmised that the isomer shift increases with a decrease in temperature, with a characteristic slope change at the structural transition in both samples studied. In both the x = 0.1 and x = 0.5 samples, a low B(hf) centred around 0.5 Tesla is seen to occur well above the structural transition temperature, the contribution from which is suppressed with a decrease in temperature. Below the structural transition temperature, a bimodal distribution of B(hf) centred at about 3 Tesla and 5 Tesla emerges, the contribution from which increases with a further decrease in temperature. Spin polarized density functional calculations suggest the occurrence of different magnetic moments at the Fe sites in the Ru substituted compounds, and provide a rationale for the experimentally observed multimodel B(hf). PMID- 25115983 TI - [Childhood granulomatous periorificial dermatitis]. AB - CASE REPORT: A 14-year-old patient of African ancestry presented with multiple papules in the perioral, perinasal and periocular areas. Histopathology showed sarcoidal granulomas. DIAGNOSIS: After exclusion of systemic sarcoidosis, the diagnosis of childhood granulomatous periorificial dermatitis was made. THERAPY: Topical treatment with erythromycin resulted in complete regression. CONCLUSION: Childhood granulomatous periorificial dermatitis is mainly observed in dark skinned children of African, Caribbean, or Asian origin. The nosological position of the dermatosis is controversial. Originally classified as sarcoidosis, childhood granulomatous periorificial dermatitis is now generally regarded as a special form of perioral dermatitis. PMID- 25115988 TI - 'Jumping around': exploring young women's behaviour and knowledge in relation to sexual health in a remote Aboriginal Australian community. AB - Sexual health indicators for young remote-living Aboriginal women are the worst of all of Australian women. This study aimed to describe and explore young women's behaviour and knowledge in relation to sexual health, as well as to provide health professionals with cross-cultural insights to assist with health practice. A descriptive ethnographic study was conducted, which included: extended ethnographic field work in one remote community over a six-year period; community observation and participation; field notes; semi-structured interviews; group reproductive ethno-physiology drawing and language sessions; focus-group sessions; training and employment of Aboriginal research assistants; and consultation and advice from a local reference group and a Cultural Mentor. Findings reveal that young women in this remote community have a very poor biomedical understanding of sexually transmitted infections and contraception. This is further compounded by not speaking English as a first language, low literacy levels and different beliefs in relation to body functions. In their sexual relationships, young women often report experiences involving multiple casual partners, marijuana use and violence. Together, the findings contribute to a better understanding of the factors underlying sexual health inequity among young Aboriginal women in Australia. PMID- 25115989 TI - Treatment of bone metastases in urologic malignancies. AB - The skeletal system is the most common site of metastatic cancer spread. Bone metastases are often associated with severe morbidity, pain and functional impairment. Timely diagnosis and proper treatment may decrease morbidity, improve quality of life and in some cases even improve survival. External beam radiotherapy may effectively give pain relief in patients with painful bone metastases. In bone metastases from castration-resistant prostate cancer or urothelial bladder cancer, treatment with zoledronic acid or denosumab may reduce skeletal-related events. In contrast to castration-resistant prostate cancer, in patients with bone metastases from bladder cancer such treatment may even improve survival. On the other hand, the efficacy of these agents is questionable in patients with bone involvement from metastatic renal cell carcinoma or germ cell tumors. When bisphosphonates or denosumab are considered in such cases, the potential benefits of treatment should be critically weighed against the risk of side effects. In germ cell tumors, bone metastases may be cured by cisplatin based chemotherapy, however, there are only limited data on the specific management of residual disease. Oligometastases may be treated by stereotactic radiotherapy or--especially in patients with renal cell carcinoma--by surgical resection and endoprosthetic replacement. Limited data are available on the management of bone involvement in germ cell tumors. Decisions on the resection or local radiotherapy of residual disease should be individualized considering the overall response and the feasibility and risks of resection. PMID- 25115991 TI - Temperature response of denitrification and anaerobic ammonium oxidation rates and microbial community structure in Arctic fjord sediments. AB - The temperature dependency of denitrification and anaerobic ammonium oxidation (anammox) rates from Arctic fjord sediments was investigated in a temperature gradient block incubator for temperatures ranging from -1 to 40 degrees C. Community structure in intact sediments and slurry incubations was determined using Illumina SSU rRNA gene sequencing. The optimal temperature (Topt ) for denitrification was 25-27 degrees C, whereas anammox rates were optimal at 12-17 degrees C. Both denitrification and anammox exhibited temperature responses consistent with a psychrophilic community, but anammox bacteria may be more specialized for psychrophilic activity. Long-term (1-2 months) warming experiments indicated that temperature increases of 5-10 degrees C above in situ had little effect on the microbial community structure or the temperature response of denitrification and anammox. Increases of 25 degrees C shifted denitrification temperature responses to mesophilic with concurrent community shifts, and anammox activity was eliminated above 25 degrees C. Additions of low molecular weight organic substrates (acetate and lactate) caused increases in denitrification rates, corroborating the hypothesis that the supply of organic substrates is a more dominant control of respiration rates than low temperature. These results suggest that climate-related changes in sinking particulate flux will likely alter rates of N removal more rapidly than warming. PMID- 25115992 TI - Bivalirudin versus unfractionated heparin for residual thrombus burden: a frequency-domain optical coherence tomography study. AB - OBJECTIVES: This study aimed to compare the effect of bivalirudin and unfractionated heparin (UFH) on residual thrombus burden assessed by frequency domain optical coherence tomography (FD-OCT), and on angiographic indices of microvascular obstruction (MVO). BACKGROUND: The efficacy of bivalirudin to inhibit thrombus formation inside the stent during percutaneous coronary interventions (PCI) as compared to UFH is unknown. METHODS: Sixty patients with coronary artery disease who underwent post-PCI FD-OCT were studied, including 20 patients treated with bivalirudin and 40 control patients treated with UFH, matched by clinical presentation, stent characteristics, and periprocedural medications. In-stent thrombus volume, thrombus score (number of quadrants with thrombus), and thrombus type (white/red) were assessed by FD-OCT. Thrombolysis in myocardial infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and Quantitative Blush Evaluator (QuBE) score were recorded. RESULTS: Patients treated with bivalirudin showed similar thrombus volume (0.14 mm(3) [0.00-0.88] vs. 0.13 mm(3) [0.00-0.63], P = 0.962), thrombus score (10 [0-25] vs. 8 [0-21], P = 0.849) and thrombus length (1.70 mm [0.00-4.10] vs. 1.40 mm [0.00-4.05], P = 0.968], as compared with patients treated with UFH. Patients in the bivalirudin group showed lower proportion of white thrombus (55.5% vs. 78.6%, P = 0.016). There was no significant difference in TIMI flow grade, cTFC, and QuBE score between the two groups. CONCLUSIONS: The present study showed similar residual thrombus burden and angiographic indices of MVO immediately after PCI between patients treated with bivalirudin and those treated with UFH. PMID- 25115993 TI - Sterile-filtered saliva is a strong inducer of IL-6 and IL-8 in oral fibroblasts. AB - OBJECTIVES: Saliva has been implicated to support oral wound healing, a process that requires a transient inflammatory reaction. However, definitive proof that saliva can provoke an inflammatory response remained elusive. MATERIALS AND METHODS: We investigated the ability of freshly harvested and sterile-filtered saliva to cause an inflammatory response of oral fibroblasts and epithelial cells. The expression of cytokines and chemokines was assessed by microarray, RT PCR, immunoassays, and Luminex technology. The involvement of signaling pathways was determined by Western blot analysis and pharmacologic inhibitors. RESULTS: We report that sterile-filtered whole saliva was a potent inducer of IL-6 and IL-8 in fibroblasts from the gingiva, the palate, and the periodontal ligament, but not of oral epithelial cells. This strong inflammatory response requires nuclear factor-kappa B and mitogen-activated protein kinase signaling. The pro inflammatory capacity is heat stable and has a molecular weight of <40 kDa. Genome-wide microarrays and Luminex technology further revealed that saliva substantially increased expression of other inflammatory genes and various chemokines. To preclude that the observed pro-inflammatory activity is the result of oral bacteria, sterile-filtered parotid saliva, collected under almost aseptic conditions, was used and also increased IL-6 and IL-8 expression in gingiva fibroblasts. The inflammatory response was, furthermore, independent of MYD88, an adapter protein of the Toll-like receptor signaling pathway. CONCLUSIONS: We conclude that saliva can provoke a robust inflammatory response in oral fibroblasts involving the classical nuclear factor-kappa B and mitogen-activated protein kinase signaling pathway. CLINICAL RELEVANCE: Since fibroblasts but not epithelial cells show a strong inflammatory response, saliva may support the innate immunity of defect sites exposing the oral connective tissue. PMID- 25115994 TI - Evaluation of a new oral health scale of infectious potential based on the salivary microbiota. AB - OBJECTIVES: The objective of this study is to analyse the correlation of our own design of oral health scale (grades 0 and 1-better oral health vs. grades 2 and 3 poorer oral health) with the salivary microbiota. PATIENTS AND METHODS: The oral health scale we elaborated was evaluated in 100 adults (25 patients from each global oral health grade). Saliva samples collected from these patients were analysed using microbiological culture techniques, determining the presence/absence and the concentrations of some odontopathogens and periodontopathogens. RESULTS: In comparison with the global oral health grades 0 1, the grades 2-3 presented significantly higher values for the presence of odontopathogens (78 vs. 38 %; Streptococcus mutans, Lactobacillus spp. and Actinomyces spp.) and periodontopathogens (100 vs. 90 %; Aggregatibacter actinomycetemcomitans, Campylobacter spp., Fusobacterium spp. and Prevotella gingivalis). In comparison with the grades 0-1, the grades 2-3 presented significantly higher values for the concentrations (CFU/mL log10) of facultative anaerobes, strict anaerobes, odontopathogens (S. mutans, Lactobacillus spp. and Actinomyces spp.) and periodontopathogens (A. actinomycetemcomitans, Capnocytophaga spp., Campylobacter spp. and Fusobacterium spp.). CONCLUSION: Our new global oral health scale shows a positive correlation with the detection and quantification of certain odontopathogens and periodontopathogens present in the saliva, confirming their possible infectious potential. CLINICAL RELEVANCE: Our own design of oral health scale could be particularly useful for the epidemiological study of different populations, the evaluation of the influence of oral health on the development of certain systemic diseases as well as the analysis of inter- and intra-individual variability of the oral microbiota in relation to the different grades of the oral health scale. PMID- 25115997 TI - Continuous and scalable fabrication of bioinspired dry adhesives via a roll-to roll process with modulated ultraviolet-curable resin. AB - A simple yet scalable strategy for fabricating dry adhesives with mushroom-shaped micropillars is achieved by a combination of the roll-to-roll process and modulated UV-curable elastic poly(urethane acrylate) (e-PUA) resin. The e-PUA combines the major benefits of commercial PUA and poly(dimethylsiloxane) (PDMS). It not only can be cured within a few seconds like commercial PUA but also possesses good mechanical properties comparable to those of PDMS. A roll-type fabrication system equipped with a rollable mold and a UV exposure unit is also developed for the continuous process. By integrating the roll-to-roll process with the e-PUA, dry adhesives with spatulate tips in the form of a thin flexible film can be generated in a highly continuous and scalable manner. The fabricated dry adhesives with mushroom-shaped microstructures exhibit a strong pull-off strength of up to ~38.7 N cm(-2) on the glass surface as well as high durability without any noticeable degradation. Furthermore, an automated substrate transportation system equipped with the dry adhesives can transport a 300 mm Si wafer over 10,000 repeating cycles with high accuracy. PMID- 25115995 TI - Effects of sodium hypoclorite as disinfectant material previous to pulpotomies in primary teeth. AB - OBJECTIVES: Sodium hypochlorite (NaOCl) can be used to promote healing vital pulpotomies as an antibacterial agent. The aim of the present study was to histologically analyze the pulpal response of human primary teeth pulp following calcium hydroxide (CH) and mineral trioxide aggregate (MTA) pulpotomies with and without 5% NaOCl. MATERIALS AND METHODS: One hundred twenty-eight primary molars were randomly divided into two main groups according to pulpotomy material (CH/MTA) and into two subgroups according to selected cleansing agent (NaOCl/physiologic saline) used in the pulpotomy procedure. Thirty-four successfully treated teeth whose successor roots had completed formation of at least two thirds of their lengths were extracted for histological evaluation. Fisher's exact test, Pearson's Chi-square test, and Mann-Whitney U test with Bonferroni correction were used for statistical analysis. RESULTS: No significant differences in any of the tested parameters were observed between the NaOCl and physiologic saline subgroups of either the CH or MTA groups. Pulpal inflammation was significantly higher in the CH-treated teeth as compared with the MTA-treated teeth, whereas hard tissue bridge formation was significantly higher in the MTA treated teeth as compared with the CH-treated teeth but regardless of cleansing agent (p < 0.025). CONCLUSIONS: The use of NaOCl does not affect the success of CH or MTA pulpotomies. Regardless of cleansing agent, MTA was found to be superior to CH. CLINICAL RELEVANCE: The proper medicament selection is more important than the choice of cleaning agent in vital pulpotomies. PMID- 25115998 TI - Estimation of the use of antibiotics in the small ruminant industry in The Netherlands in 2011 and 2012. AB - The aim of this study was to estimate the quantity of antibiotics and classes of antibiotics used in the small ruminant industry in the Netherlands in 2011 and 2012. Twelve large veterinary practices, located throughout the Netherlands were selected for this study. All small ruminant farms associated with these practices that had complete records on the quantity of antibiotics prescribed were included. The veterinary practices provided data on all antibiotics prescribed, and the estimated animal used daily dose of antibiotics per year (AUDD/Y) was calculated for each farm. The median AUDD/Y in small ruminant farms was zero in both years (mean 0.60 in 2011, and 0.62 in 2012). The largest quantity of antibiotic use was observed in the professional goat industry (herds of >=32 goats) with a median AUDD/Y of 1.22 in 2011 and 0.73 in 2012. In the professional sheep industry (flocks of >=32 sheep), the median AUDD/Y was 0 in 2011 and 0.10 in 2012. In the small scale industry (flocks or herds of <32 sheep or goats), the median AUDD/Y never exceeded 0. The most frequently prescribed antibiotics in the small scale industry and professional sheep farms belonged to the penicillin class. In professional goat farms, antibiotics of the aminoglycoside class were most frequently prescribed. This study provides the first assessment on the quantity of antibiotic use in the small ruminant industry. Given a comparable attitude towards antibiotic use, these results might be valid for small ruminant populations in other north-western European countries as well. The antibiotic use in the small ruminant industry appeared to be low, and is expected to play a minor role in the development of antibiotic resistance. Nevertheless, several major zoonotic bacterial pathogens are associated with the small ruminant industry, and it remains important that antibiotics are used in a prudent way. PMID- 25116000 TI - Development of an in vitro screen for compound bioaccumulation in Haemonchus contortus. AB - The objective of the current study was to establish an in vitro screen and a highly sensitive analytical assay to delineate key physicochemical properties that favor compound bioaccumulation in the L3 life stage of a Haemonchus contortus isolate. Time-dependent studies revealed that absorption and elimination kinetics during the first 6 hr of exposure were sufficient to achieve maximum bioaccumulation for the majority of compounds tested. In subsequent studies, the larvae were incubated for 6 hr in a medium containing 146 compounds (5 MUM initial concentration), including both human and veterinary medicines, characterized by a broad range of physicochemical properties. Bioaccumulation of the compounds by the nematodes was determined, and multiple physicochemical descriptors were selected for correlation. Data analysis using Bayes classification model and partial least-square regression revealed that clogD7.4, rotatable bond, E-state, and hydrogen bond donor each correlated with compound bioaccumulation in H. contortus L3. The finding that lipophilicity was critical for transcuticle compound permeation was consistent with previous studies in other parasitic species and in adult H. contortus . The finding of additional physicochemical properties that contribute to compound conformational flexibility, polarity, and electrotopological state shed light on the mechanisms governing transcuticle permeation. The relatively poor correlation between transcuticle and transmembrane permeation indicated the distinct mechanisms of compound permeation, likely due to the different constituents, and their contributions to overall transport function, of the lipid membranes and the porous collagen barrier of the nematode cuticle. Our study, for the first time, establishes a high-throughput screen for compound bioaccumulation in a parasitic nematode and further elucidates physicochemical factors governing transcuticular permeation of compounds. Application of this methodology will help explain the basis for discrepancies observed in receptor binding and whole organism potency assays and facilitate incorporation of drug delivery principles in the design of candidate anthelmintics. PMID- 25115999 TI - Cognitive impairment in myotonic dystrophy type 1 is associated with white matter damage. AB - OBJECTIVE: To investigate grey (GM) and white matter (WM) abnormalities and their effects on cognitive and behavioral deficits in a large, phenotypically and genotypically well-characterized cohort of classic adult (aDM1, age at onset >= 20 years) or juvenile (jDM1, age at onset <20 years) patients with myotonic dystrophy type 1 (DM1). METHODS: A case-control study including 51 DM1 patients (17 jDM1 and 34 aDM1) and 34 controls was conducted at an academic medical center. Clinical, cognitive and structural MRI evaluations were obtained. Quantitative assessments of regional GM volumes, WM hyperintensities (WMHs), and microstructural WM tract damage were performed. The association between structural brain damage and clinical and cognitive findings was assessed. RESULTS: DM1 patients showed a high prevalence of WMHs, severe regional GM atrophy including the key nodes of the sensorimotor and main cognitive brain networks, and WM microstructural damage of the interhemispheric, corticospinal, limbic and associative pathways. WM tract damage extends well beyond the focal WMHs. While aDM1 patients had severe patterns of GM atrophy and WM tract damage, in jDM1 patients WM abnormalities exceeded GM involvement. In DM1, WMHs and microstructural damage, but not GM atrophy, correlated with cognitive deficits. CONCLUSIONS: WM damage, through a disconnection between GM structures, is likely to be the major contributor to cognitive impairment in DM1. Our MRI findings in aDM1 and jDM1 patients support the hypothesis of a degenerative (premature aging) origin of the GM abnormalities and of developmental changes as the principal substrates of microstructural WM alterations in DM1. PMID- 25116001 TI - Treatment of alpha(0)-thalassemia (--(SEA)/--(SEA)) via serial fetal and post natal transfusions: Can early fetal intervention improve outcomes? AB - OBJECTIVE AND IMPORTANCE: Homozygous Southeast Asian alpha-thalassemia mutation ( -(SEA)/--(SEA)) results in deletion of all alpha-globin genes (alpha(0) thalassemia). Since all alpha-globin chains are absent, hemoglobin F cannot be synthesized, and hemoglobin Bart's becomes the dominant fetal hemoglobin. Hemoglobin Bart's is a gamma tetramer with a very high oxygen affinity, thus oxygen delivery to the tissues is poor. Clinical manifestations include severe fetal anemia, hydrops fetalis, fetal demise, and high risk of neurodevelopmental impairment in the rare survivors. CLINICAL PRESENTATION: A 39-year-old Vietnamese woman presented to our center at 28 0/7 weeks' gestation with fetal alpha(0) thalassemia (--(SEA)/--(SEA) type deletion) and ultrasound markers suggestive of severe fetal anemia. INTERVENTION: The fetus was treated with four intrauterine transfusions followed by post-natal chronic transfusions. Formal neurodevelopmental testing (Battelle Developmental Inventory, Second Edition) was performed at 18 months of age, and the developmental quotient was 93 (32nd percentile) with all subdomains noted within normal limits, indicating overall intact neurodevelopment. CONCLUSION: We posit that earlier diagnosis and fetal treatment, prior to clinical findings suggestive of fetal anemia, may improve long-term outcomes by enhancing oxygen delivery to the tissues of the developing fetus. PMID- 25116002 TI - Decreased inter-hemispheric connectivity in anterior sub-network of default mode network and cerebellum: significant findings in major depressive disorder. AB - The issue of inter-hemispheric connectivity is an emerging new area in understanding the pathophysiology of depression. This study was designed to analyse the pattern of inter-hemispheric connectivity in patients with major depressive disorder (MDD). The resting-state functional magnetic resonance imaging (RFMRI) was acquired in all enrolled patients and controls. We used a method of voxel-mirrored homotopic connectivity (VMHC) to estimate the significant differences in inter-hemispheric connectivity between 44 patients with first-episode medication-naive MDD and 27 normal controls. The patients and controls were matched for age and gender. The patients with first-episode medication-naive MDD showed lower VMHC than normal controls in bilateral medial frontal cortex, anterior cingulate and cerebellar posterior lobe. The strength of inter-hemispheric connectivity VMHC value was negatively correlated with clinical severity of MDD. From the results, we suggested that decreased inter-hemispheric connectivity in the anterior sub-network of the default mode network and the cerebellar posterior lobe might represent an emerging finding in the pathophysiology for MDD. PMID- 25116003 TI - Multicolour nonlinearly bound chirped dissipative solitons. AB - The dissipative soliton regime is one of the most advanced ways to generate high energy femtosecond pulses in mode-locked lasers. On the other hand, the stimulated Raman scattering in a fibre laser may convert the excess energy out of the coherent dissipative soliton to a noisy Raman pulse, thus limiting its energy. Here we demonstrate that intracavity feedback provided by re-injection of a Raman pulse into the laser cavity leads to formation of a coherent Raman dissipative soliton. Together, a dissipative soliton and a Raman dissipative soliton (of the first and second orders) form a two (three)-colour stable complex with higher total energy and broader spectrum than those of the dissipative soliton alone. Numerous applications can benefit from this approach, including frequency comb spectroscopy, transmission lines, seeding femtosecond parametric amplifiers, enhancement cavities and multiphoton fluorescence microscopy. PMID- 25116005 TI - Back to the future: examining type 2 diabetic vasculature using the gestational diabetic placenta. AB - Understanding the association between the intrauterine hyperglycemic milieu and the development of adult diabetic vasculopathy is of particular relevance in India, where diabetes and vascular disease are prevalent. The gestational diabetes mellitus placenta is a valuable tool to examine blood vessels that have been exposed to hyperglycemic cues. We report an interesting observation in a cohort of gestational diabetes mellitus foetal placental vasculature from South India. Transmission electron microscopy demonstrated pericyte detachment and pericyte ghost cells reminiscent of adult type 2 diabetic retinopathy, in gestational diabetes mellitus foetal placental blood vessels that were not observed in non-gestational diabetes mellitus placentas (p <=0.001). Endothelial cell irregularity was observed in 76% gestational diabetes mellitus foetal blood vessels as compared with 10.4% non-gestational diabetes mellitus placental vasculature (p <=0.001). Other abnormalities noted in gestational diabetes mellitus placenta included mitochondrial abnormalities, increased micro vessel density and thickening of basement membranes. These results suggest that adult type 2 diabetic vasculopathy has developmental origins in utero. PMID- 25116006 TI - Multiple approaches to predicting oxygen and glucose consumptions by HepG2 cells on porous scaffolds in an axial-flow bioreactor. AB - In this study, the distribution of oxygen and glucose was evaluated along with consumption by hepatocytes using three different approaches. The methods include (i) Computational Fluid Dynamics (CFD) simulation, (ii) residence time distribution (RTD) analysis using a step-input coupled with segregation model or dispersion model, and (iii) experimentally determined consumption by HepG2 cells in an open-loop. Chitosan-gelatin (CG) scaffolds prepared by freeze-drying and polycaprolactone (PCL) scaffolds prepared by salt leaching technique were utilized for RTD analyses. The scaffold characteristics were used in CFD simulations i.e. Brinkman's equation for flow through porous medium, structural mechanics for fluid induced scaffold deformation, and advection-diffusion equation coupled with Michaelis-Menten rate equations for nutrient consumption. With the assumption that each hepatocyte behaves like a micro-batch reactor within the scaffold, segregation model was combined with RTD to determine exit concentration. A flow rate of 1 mL/min was used in the bioreactor seeded with 0.6 * 10(6) HepG2 cells/cm(3) on CG scaffolds and oxygen consumption was measured using two flow-through electrodes located at the inlet and outlet. Glucose in the spent growth medium was also analyzed. RTD results showed distribution of nutrients to depend on the surface characteristics of scaffolds. Comparisons of outlet oxygen concentrations between the simulation results, and experimental results showed good agreement with the dispersion model. Outlet oxygen concentrations from segregation model predictions were lower. Doubling the cell density showed a need for increasing the flow rate in CFD simulations. This integrated approach provide a useful strategy in designing bioreactors and monitoring tissue regeneration. PMID- 25116004 TI - The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system. AB - Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients. DN is generally preceded by albuminuria, which frequently remains elevated despite treatment in patients with T2DM. Optimal treatment and prevention of DN may require an early, intensive, multifactorial approach, tailored to simultaneously target all modifiable risk factors. Regular monitoring of renal function, including urinary albumin excretion, creatinine clearance and glomerular filtration rate, is critical for following any disease progression and making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without additional risk of hypoglycaemia, and may also reduce albuminuria. Further investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is underway. PMID- 25116008 TI - [Biochemical markers after trauma]. PMID- 25116007 TI - Activation of nuclear factor kappa B in the hepatic stellate cells of mice with schistosomiasis japonica. AB - Schistosomiasis japonica is a serious tropical parasitic disease in humans, which causes inflammation and fibrosis of the liver. Hepatic stellate cells (HSCs) are known to play an important role in schistosome-induced fibrosis, but their role in schistosome-induced inflammation is still largely unknown. Here, we use a murine model of schistosomiasis japonica to investigate the role that nuclear factor kappa B (NF-kappaB), a critical mediator of inflammatory responses, plays in schistosome-induced inflammation. We revealed that NF-kappaB was significantly activated in HSCs at the early stage of infection, but not at later stages. We also show that the expression levels of several chemokines regulated by NF-kappaB signaling (Ccl2, Ccl3 and Ccl5) were similarly elevated at early infection. TLR4 signaling, one of the strongest known inducers of NF-kappaB activation, seemed not activated in HSCs post-infection. Importantly, we found that levels of miR 146 (a known negative regulator of NF-kappaB signaling) in HSCs opposed those of NF-kappaB signaling, elevating at later stage of infection. These results indicate that HSCs might play an important role in the progression of hepatic schistosomiasis japonica by linking liver inflammation to fibrosis via NF-kappaB signaling. Moreover, our work suggests that miR-146 appeared to regulate this process. These findings are significant and imply that manipulating the function of HSCs by targeting either NF-kappaB signaling or miR-146 expression may provide a novel method of treating hepatic schistosomiasis japonica. PMID- 25116009 TI - [Biomarkers in pediatric polytrauma]. AB - BACKGROUND: Trauma represents one of the leading causes of death in children. Beside an injury pattern that differs from adult trauma patients, children seem to develop multiple organ dysfunction syndrome (MODS) less frequently. Compared to adult MODS, pediatric MODS has also been described to occur earlier in the posttraumatic course. METHOD: Biomarkers for early identification of patients at high-risk for posttraumatic complications are of high clinical relevance. However, little is known from clinical studies about the relevance of biomarkers during the posttraumatic course. AIM: Therefore, the purpose of this review is to summarize current knowledge on this topic in order to investigate the prognostic significance of different parameters. PMID- 25116010 TI - [Microarrays as biomarkers in trauma]. AB - BACKGROUND: The traditional hypothesis-driven scientific approach cannot so far sufficiently elucidate complex pathophysiologies, such as posttraumatic systemic inflammation and subsequent multiple organ failure. This complex system includes different biological and functional levels, the genome, the transcriptome, the proteome, the biome (cells), the organs and finally the whole organism. METHODS: Microarray techniques enable a simultaneous search for these different biological levels and their functional relationships on a large scale and to discover new functional pathways and networks and potentially new biomarkers for different pathologies. Microarray technologies lead to a new paradigm in science, the hypothesis-generating approach. AIM: This article reviews important microarray findings in trauma and systemic inflammation research and discusses potentials and limitations of these biotechnological screening methods. PMID- 25116011 TI - [Diagnostic biomarkers in traumatic brain injury]. AB - BACKGROUND: Despite advances in medicine in head trauma management, traumatic brain injury (TBI) still remains a serious health concern, affecting people regardless of age. It is a leading cause of morbidity and mortality particularly in children and young adults. Therefore, studies are being carried out to try to establish reliable biomarkers to improve the accuracy of TBI diagnosis and associated secondary pathologies. METHODS: Implementation of valid TBI biomarkers could possibly reduce the necessity to use computed cranial tomography (CCT), especially in patients suffering from mild TBI to rule out intracranial bleeding. AIM: This review provides a critical assessment of biomarkers currently under investigation and their clinical value for the diagnosis, treatment and outcome prediction of TBI. PMID- 25116012 TI - [Cytokines as biomarkers in polytraumatized patients]. AB - BACKGROUND: Multiple trauma can lead to posttraumatic complications such as systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and sepsis. Currently, these complications are monitored using clinical and organ-specific parameters. The immune system is activated by trauma. Cytokines, which are the messenger molecules of this system, can be determined in serum. Furthermore, they are associated with the intensity of the inflammatory and anti-inflammatory reactions. AIM: This review describes clinical studies that measured cytokines such as TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 to prognosticate posttraumatic complications. On the other hand, IL-6 can be helpful in deciding which primary operation to perform, i.e., external fixator or intramedullary nail. Moreover, IL-6 indicates the strength of the immune reaction. Thereby, it may help in determining the optimal time for secondary surgery. PMID- 25116014 TI - [Retraction Note to: Biodegradable screw vs a press-fit bone plug fixation for ACL reconstruction. A prospective randomized study]. PMID- 25116013 TI - [Scapholunate lesions]. AB - Injuries to the scapholunate ligament are the most frequent cause of carpal instability. Therefore, if a scapholunate lesion is not diagnosed, it may result in a severe dysfunction of the wrist. This review describes the anatomy, and the kinematics of the wrist with an intact as well as a disrupted scapholunate ligament. The diagnostic of an isolated ligament lesion and a ligament injury associated with a fracture of the distal radius is presented. Finally, an algorithm for treatment based on the stage of injury is proposed. PMID- 25116016 TI - [Non-valvular atrial fibrillation: direct thrombin inhibitors versus VKA]. PMID- 25116017 TI - [Does transcatheter aortic-valve replacement reduce mortality?--TAVR: good prognosis due to improved protheses]. PMID- 25116015 TI - Targeted high-throughput sequencing identifies pathogenic mutations in KCNQ4 in two large Chinese families with autosomal dominant hearing loss. AB - Autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous, among them, KCNQ4 is one of the most frequent disease-causing genes. More than twenty KCNQ4 mutations have been reported, but none of them were detected in Chinese mainland families. In this study, we identified a novel KCNQ4 mutation in a five generation Chinese family with 84 members and a known KCNQ4 mutation in a six generation Chinese family with 66 members. Mutation screening of 30 genes for ADNSHL was performed in the probands from thirty large Chinese families with ADNSHL by targeted region capture and high-throughput sequencing. The candidate variants and the co-segregation of the phenotype were verified by polymerase chain reaction (PCR) amplification and Sanger sequencing in all ascertained family members. Then we identified a novel KCNQ4 mutation p.W275R in exon 5 and a known KCNQ4 mutation p.G285S in exon 6 in two large Chinese ADNSHL families segregating with post-lingual high frequency-involved and progressive sensorineural hearing loss. This is the first report of KCNQ4 mutation in Chinese mainland families. KCNQ4, a member of voltage-gated potassium channel family, is likely to be a common gene in Chinese patients with ADNSHL. The results also support that the combination of targeted enrichment and high-throughput sequencing is a valuable molecular diagnostic tool for autosomal dominant hereditary deafness. PMID- 25116018 TI - [Treatment of acute renal failure in Germany: a structural analysis]. AB - INTRODUCTION: There are no reliable data on the structure and practice of the care of critically ill patients with acute renal failure in Germany. METHODS: We carried out a detailed survey by sending a questionnaire to 2265 German Intensive Care Units. The questionnaire contained 19 questions regarding renal replacement therapy. RESULTS: 423 German intensive care units participated in the survey. Most of the ICUs are headed interdisciplinary (47%) or by anesthesiologists (30%), with significant differences depending on the size of the clinic, with primarily interdisciplinary management in smaller clinics. The offered type of renal replacement therapy varies significantly, the smaller the house the fewer methods are available. Thus, intermittent dialysis procedures are offered only in 35% of hospitals with up to 400 beds. The indication for the initiation of acute renal replacement therapy in intensive care is provided predominantly (53%) by an anesthesiologist. A nephrologist is only involved in 22% of all intensive care units. The indication is based primarily on a "clinical criteria", but these are poorly defined. CONCLUSION: Our results demonstrate the need for cross disciplinary standards for the treatment of acute renal failure in German intensive care units. PMID- 25116020 TI - [45-year-old woman with iron deficiency anemia]. PMID- 25116019 TI - [Endovascular therapy of an iatrogenic renal-artery-perforation after fenestrated aortic-repair (fEVAR)]. AB - HISTORY AND ADMISSION FINDINGS: A 75-year-old patient was initially hospitalized for therapy-evaluation of a an acquaint infrarenal abdominal-aortic-aneurysm, with a maximum diameter of 5.3 cm. Medical history showed a known contained rupture of the aneurysm. Except for a substituted Hypothyroidism and a COPD Stadium II (GOLD), there were no other previous diseases known. EXAMINATIONS: Laboratory showed a slight normochrome, normocytic anemia (hemoglobin 13 g/dl, MCV and MCH were normal) together with a decreased total amount of erythrocytes of 3.89/pl. TSH value was increased significantly at 7.960 mU/l. Initially creatinine was measured at 1.02 mg/dl. Sonography and CT-scan of the abdominal vessels had shown no new insights other than the aneurysm of the abdominal aorta. A surgical revision was indicated. TREATMENT AND COURSE: After primarily uncomplicated implantation of a fenestrated EVAR, the patient showed a progressive hemoglobin loss concomitant with a considerable increase of renal retention parameters. A "spurium"/false aneurysm of the right renal artery was found, which moreover showed a retroperitoneal bleeding. The patient subsequently underwent successful endovascular therapy in our clinic and was dismissed from the hospital in good condition and without further complications. Follow up controls showed no signs of new pathologies. CONCLUSION: "Direct" post-operative complications after EVAR are a rarity. In our case, the interventional endovascular approach of the bleeding from the right renal artery was a successful and sufficient treatment of the potentially life-threatening complication. PMID- 25116023 TI - [Venous valve prosthesis--close to the biological model]. PMID- 25116022 TI - [New diagnostic tool for individual monitoring of urolithiasis risk and other metabolic diseases]. AB - Urinary composition is the result of the interplay of all metabolic processes, including all metabolites and toxins produced. Any change in urine composition influences urinary supersaturation, the major thermodynamic driving force of crystal formation. Urolithiasis is a wide-spread disease with a prevalence rate of 4% to 10%. Formation risk of calcium-oxalate, by far the most common mineral in uroliths, is quantified by the Bonn-Risk-Index (BRI). The BRI measures induced crystal growth within native urine and shows superior diagnostic sensitivity and specificity compared to other urolithiasis risk indices. The concept of BRI quick test presented in this work allowes even untrained persons to easily determine the urolithiasis risk. Many diseases lack a simple, easily accessible and cost effective diagnostic approach to monitor their course and treatment success. Since BRI takes into account every constituent of native urine, it can be used to monitor a wide range of metabolic diseases. PMID- 25116021 TI - [Non-cystic fibrosis bronchiectasis: diagnosis and treatment]. AB - Bronchiectasis is the term used for irreversibly dilated airways. Exact epidemiological information on the frequency of bronchiectasis is not available, but the morphological findings are increasingly detected and the associated syndrome is more frequently diagnosed due to improved imaging techniques and increased awareness among chest physicians. The workup of these patients includes a wide panel of investigations guided by patient history and clinical presentation. Despite thorough evaluation the aetiology frequently remains unclear. Chronic infection with Pseudomonas aeruginosa is associated with a severe course of the disease and its detection has impacts on the therapeutic management. Chest physiotherapy, mucoactive substances and antibiotics are the mainstay of therapy. In this review the evaluation of bronchiectasis and the recent therapeutic insights for non-cystic fibrosis bronchiectasis are discussed. PMID- 25116025 TI - ["Burnout"--is it a disease or rather a consequence of (work-) stress?]. AB - Burnout is a work related health impairment comprising three dimensions: emotional exhaustion, depersonalisation and reduced personal accomplishment. Not least because of the highly frequented term "burnout" within the German speaking area, there is a rising interest in the connection of work related stress and psychological and somatic complaints. Burnout is not a disease in the proper sense but a physiological construct. Coherence between work related stress and the development of psychological and somatic diseases has been proven by many studies. However burnout requires a differential diagnostic categorisation. Therapeutic procedures and prevention measures should be initiated based on the forms and categorisation of work related stress. PMID- 25116024 TI - [If the general practitioner has to decide: what is the evidence for the selection of antidepressants?]. AB - The review summarises the evidence supporting the choice of an antidepressant in primary care. We report current guidance on the choice of antidepressants and the current use of antidepressants in Germany. Evidence for the comparative efficacy of modern antidepressants, such as venlafaxine, duloxetine or agomelatine will be summarized with respect to depressive and accompanying symptoms. Furthermore, differences in adverse events between antidepressants will be reviewed. PMID- 25116031 TI - Bandgap-engineered CdxZn1-xO nanowires as active regions for green-light-emitting diodes. AB - A green-light-emitting diode device was fabricated based on a p-type Sb-doped ZnO segments/Cd-alloyed ZnO/n-type ZnO film/heteronanowires array structure. The structures and chemical components of the heteronanowire sample were studied by energy dispersive spectrometer, x-ray photoelectron spectrometer, etc, from which the statuses of Cd and Sb in the sample were confirmed. Spatially resolved photoluminescence measurement on a single heteronanowire revealed a large bandgap shift in the Cd(x)Zn(1 - x)O active region. In electroluminescence characterizations, the device showed that the green emission was centered at 550 nm, suggesting the successful formation and functioning of the double heterojunction nanowire light-emitting diodes. PMID- 25116026 TI - A proteomic glimpse into the initial global epigenetic changes during HIV infection. AB - HIV-1 replication requires the insertion of viral DNA into the host genome, which is catalyzed by HIV-1 integrase. This integration event can lead to vast changes in the chromatin landscape and gene transcription. In this study, we sought to correlate the extensive changes of histone PTM abundances with the equally dynamic shifts in host transcriptional activity. To fully capture the changes that were occurring during the course of HIV-infection, we performed time-courses in which we extracted both histones and mRNA from HIV-infected, UV-inactivated HIV-infected and mock-infected SUP-T1 cells. We then analyzed the alterations to histone PTM profiles using nano-LC-MS/MS, as well as the expression of chromatin associated enzymes, such as histone deacetylases, acetyltransferases, demethylases, methyltransferases, and histone chaperone proteins. As expected, we observed major changes in histone PTM abundances, which we linked to massive fluctuations in mRNA expression of associated chromatin enzymes. However, we find few differences between HIV and HIVUV (UV-inactivated) infection, which suggests that initial histone PTM changes during HIV infection are from the host in response to the infection, and not due to the HIV virus manipulating the transcriptional machinery. We believe that these preliminary experiments can provide a basis for future forays into targeted manipulations of histone PTM regulated aspects of HIV progression through its replication cycle. PMID- 25116032 TI - In vitro three-dimensional bone tissue models: from cells to controlled and dynamic environment. AB - Most of our knowledge of bone cell physiology is derived from experiments carried out in vitro on polystyrene substrates. However, these traditional monolayer cell cultures do not reproduce the complex and dynamic three-dimensional (3D) environment experienced by cells in vivo. Thus, there is a growing interest in the use of 3D culture systems as tools for understanding bone biology. These in vitro-engineered systems, less complex than in vivo models, should ultimately recapitulate and control the main biophysical, biochemical, and biomechanical cues that define the in vivo bone environment, while allowing their monitoring. This review focuses on state-of-the-art and the current advances in the development of 3D culture systems for bone biology research. It describes more specifically advantages related to the use of such systems, and details main characteristics and challenges associated with its three main components, that is, scaffold, cells, and perfusion bioreactor systems. Finally, future challenges for noninvasive imaging technologies are addressed. PMID- 25116033 TI - New causes of central precocious puberty: the role of genetic factors. AB - A pivotal event in the onset of puberty in humans is the reemergence of the pulsatile release of the gonadotropin-releasing hormone (GnRH) from hypothalamic neurons. Pathways governing GnRH ontogeny and physiology have been discovered by studying animal models and humans with reproductive disorders. Recent human studies implicated the activation of kisspeptin and its cognate receptor (KISS1/KISS1R) and the inactivation of MKRN3 in the premature reactivation of GnRH secretion, causing central precocious puberty (CPP). MKRN3, an imprinted gene located on the long arm of chromosome 15, encodes makorin ring finger protein 3, which is involved in ubiquitination and cell signaling. The MKRN3 protein is derived only from RNA transcribed from the paternally inherited copy of the gene due to maternal imprinting. Currently, MKRN3 defects represent the most frequent known genetic cause of familial CPP. In this review, we explored the clinical, hormonal and genetic aspects of children with sporadic or familial CPP caused by mutations in the kisspeptin and MKRN3 systems, essential genetic factors for pubertal timing. PMID- 25116034 TI - Therapeutic apheresis in Asia: An Indonesia single center experience. AB - In developing countries, like Indonesia, apheresis is still a relative new procedure. Nowadays, therapeutic apheresis procedures are performed in the field of hematology and neurology, especially in the teaching hospitals in Indonesia. Therapeutic apheresis procedure, that is, leukocytapheresis, therapeutic plasma exchange (TPE), and thrombocytapheresis are already performed. In the period 2009 2013, 204 apheresis procedures in 137 patients to reduce the leukocytes, 72 TPE procedures in 17 patients, and 14 thrombocyte reductions were performed in the Sardjito hospital, Yogyakarta, Indonesia. In the future, to improve the therapeutic apheresis implementation, it is important to increase the insurance coverage and also should be considered to introduce the apheresis medicine into the curriculum of appropriate physician programs in Indonesia. Especially in Indonesia, a lot of efforts are still being needed to improve implementation of therapeutic apheresis. PMID- 25116035 TI - The relation of standardized mental health screening and categorical assessment in detained male adolescents. AB - Having an effective triage tool is an important step toward a careful use of the restricted time and qualified personnel to perform comprehensive psychiatric assessment in juvenile justice settings. The aims of this study were to examine the construct validity of the Massachusetts Youth Screening Inventory-second version (MAYSI-2), and its likelihood to identify youths who might have a psychiatric disorder. Data from up to 781 male adolescents (mean age = 16.73 years) were gathered as part of the standardized mental health screening and assessment in two all-male Youth Detention Centers in the Netherlands. Categorical assessments were based on two structured diagnostic interviews. Sensitivity, specificity, positive and negative predictive values, and the area under the curve were calculated to evaluate the likelihood of the MAYSI-2 to identify youths with a psychiatric disorder. Youths with a disorder scored significantly higher on the corresponding MAYSI-2 subscale than youths without a disorder. In the total sample, 70 % of the youths with a disorder met the Caution cut-off criteria on at least one MAYSI-2 scale, while youths without a psychiatric disorder were very unlikely to meet cut-off criteria for multiple MAYSI-2 scales. Overall, the sensitivity was slightly better when analyses were repeated in groups of youths from various ethnic origins. The findings supported the construct validity of the Dutch MAYSI-2 and suggested that the MAYSI-2 is a valid mental health screening tool that may serve relatively well as a triage tool. Its effectiveness, however, may differ between ethnic groups. PMID- 25116036 TI - Enrolment of children and adolescents in psychosocial care: more likely with low family social support and poor parenting skills. AB - Knowledge about determinants of child and adolescent enrolment in psychosocial care concerns only single types of care and usually only socio-demographic factors. The social environment is also a likely key determinant but evidence is lacking. The aim of this study was to examine the associations between family social support, parenting skills and child and adolescent enrolment in psychosocial care. We obtained data on 1,331 children (response rate 56.6%), 4-18 years old, enrolled in preventive child health care, and child and adolescent social care and mental health care because of psychosocial problems, and on 463 children (response rate 70.3%) not enrolled in psychosocial care. Results showed that enrolment in psychosocial care was associated with low family social support (odds ratio; 95%-confidence interval: 3.2; 2.4-4.4), and with poor parenting skills, i.e. poor supervision (1.5; 1.1-2.1) and inconsistent disciplining (1.5; 1.1-2.1). Children's psychosocial problems partially mediated the associations with family social support and completely with parenting skills. Children's problems did not moderate the associations. Positive parenting was not associated with care enrolment. We conclude that low family social support and poor parenting are important factors associated with enrolment, in particular because they are associated with more frequent occurrence of children's psychosocial problems. This implies that professionals and policymakers need to be aware that factors in children's social environment are related with enrolment in psychosocial care, in addition to children's psychosocial problems. PMID- 25116037 TI - Error-monitoring in an everyday task in people with Alzheimer-type dementia: observations over five years of performance decline. AB - Research suggests that, although everyday action errors increase significantly with dementia progression, accomplishment of the task remains high, even in severe dementia. We used archive observational data charting progressive decline in everyday task performance to explore error-monitoring over a 5-year period in four people with dementia. None of the participants showed effective error monitoring during their execution of their established tea-making routine: Over 5 years and into more severe stages of dementia, errors increased, but there was no reactive increase from our participants in error-monitoring. Training to error monitor routine tasks may be an appropriate target for further study. PMID- 25116038 TI - Publishing individual surgeons' death rates prompts risk averse behaviour. PMID- 25116039 TI - Design considerations for electrode buffer layer materials in polymer solar cells. AB - Electrode buffer layers in polymer-based photovoltaic devices enable highly efficient devices. In the absence of buffer layers, we show that diode rectification is lost in ITO/P3HT:PCBM/Ag (ITO = indium tin oxide; P3HT = poly(3 hexylthiophene); PCBM = phenyl C61-butyric acid methyl ester) devices due to nonselective charge injection through the percolated phase pathways of a bulk heterojunction active layer. Charge-selective injection, and thus rectification and device function, can be regained by placing thin, polymeric buffer layers that break the direct electrode-active layer contact. Additionally, we show that strong active layer-buffer layer interactions lead to unwanted vertical phase separation and a kinked current-voltage curve. Device function is regained, increasing power conversion efficiency from 3.6% to 7.2%, by placing a noninteracting layer between the buffer and active layer. These results guide the design and selection of future polymeric electrode buffer layers for efficient polymer solar cell devices. PMID- 25116042 TI - Positive selection of Wharton's jelly-derived CD105(+) cells by MACS technique and their subsequent cultivation under suspension culture condition: A simple, versatile culturing method to enhance the multipotentiality of mesenchymal stem cells. AB - OBJECTIVE: Wharton's jelly (WJ), an appropriate source of mesenchymal stem cells (MSCs), has been shown to have a wide array of therapeutic applications. However, the WJ-derived MSCs are very heterogeneous and have limited expression of pluripotency markers. Hence, improvement of their culture condition would promote the efficiency of WJ-MSCs. This study aims to employ a simple method of cultivation to obtain WJ-MSCs which express more pluripotency markers. METHODS: CD105(+) cells were separated by magnetic-associated (activated) cell sorting from umbilical cord mucous tissue. CD105(+) cells were added to Methocult medium diluted in alpha-minimum essential medium (alpha-MEM) and seeded in poly(2 hydroxyethyl methacrylate) (poly-HEMA)-coated plates for suspension culture preparation. Differentiation capacity of isolated cells was evaluated in the presence of differentiation-inducing media. The expression of pluripotency markers such as Oct3/4, Nanog, and Sox2 was also analyzed by RT-PCR and western blot techniques. Moreover, immunocytochemistry was performed to detect alpha smooth muscle actin (antigene) (alpha-SMA) protein. RESULTS: WJ-MSCs grew homogeneously and formed colonies when cultured under suspension culture conditions (Non-adhesive WJ-MSCs). They maintained their growth ability in both adherent and suspension cultures for several passages. Non-adhesive WJ-MSCs expressed Oct3/4, Nanog, and Sox2 both at transcriptional and translational levels in comparison to those cultured in conventional adherent cultures. They also expressed alpha-SMA protein. DISCUSSION: In this study, we isolated WJ-MSCs using a slightly modified culture condition. Our simple non-genetic method resulted in a homogeneous population of WJ-MSCs, which highly expressed pluripotency markers. CONCLUSION: In the future, more multipotent WJ-MSCs can be harnessed as a non-embryonic source of MSCs in MSC-based cell therapy. PMID- 25116043 TI - Why sigma-1 receptor dysfunction might confer vulnerability to cannabis-induced psychosis. PMID- 25116045 TI - Enhanced production of fatty alcohols by engineering the TAGs synthesis pathway in Saccharomyces cerevisiae. AB - The production of fatty acid-derived chemicals has received a great deal of attention in recent years. In yeast cells, the main storage forms of fatty acids are TAGs. However, the conversion of TAGs into fatty acid derivatives suffers from a practical standpoint. Herein, a more direct strategy was applied to accumulate cellular fatty acyl-CoAs in Saccharomyces cerevisiae, which are the activated forms of fatty acids and used as important precursors for various converting enzymes. The dga1 gene was deleted to block the fatty acyl-CoAs dependent pathway of TAGs synthesis and a significant decrease in lipid content was observed. The FAR gene was cloned and overexpressed in the wild type strain and gene disrupted strain, to convert the fatty acyl-CoAs to the corresponding fatty acid derivatives. The metabolic engineered pathway resulted in enhanced production of fatty alcohols. Compared with the wild type strain with overexpressed FAR gene, the yield of fatty alcohols in the Deltadga1 strain with FAR was dramatically increased: the intracellular fatty alcohols increased from 26 mg/L to 45 mg/L, while the extracellular fatty alcohols increased from 2.2 mg/L to 4.3 mg/L. By optimizing the culture medium with increased carbon concentration and limited nitrogen concentration, the fatty alcohols yield in the Deltadga1 strain with FAR was further increased to 84 mg/L in cells and 14 mg/L secreted in broth. The results in this study demonstrated the feasibility of using the designed strategy to solve the bottleneck in utilizing TAGs for fatty acid derivatives production. PMID- 25116044 TI - Mitochondrial DNA from El Mirador cave (Atapuerca, Spain) reveals the heterogeneity of Chalcolithic populations. AB - Previous mitochondrial DNA analyses on ancient European remains have suggested that the current distribution of haplogroup H was modeled by the expansion of the Bell Beaker culture (ca 4,500-4,050 years BP) out of Iberia during the Chalcolithic period. However, little is known on the genetic composition of contemporaneous Iberian populations that do not carry the archaeological tool kit defining this culture. Here we have retrieved mitochondrial DNA (mtDNA) sequences from 19 individuals from a Chalcolithic sample from El Mirador cave in Spain, dated to 4,760-4,200 years BP and we have analyzed the haplogroup composition in the context of modern and ancient populations. Regarding extant African, Asian and European populations, El Mirador shows affinities with Near Eastern groups. In different analyses with other ancient samples, El Mirador clusters with Middle and Late Neolithic populations from Germany, belonging to the Rossen, the Salzmunde and the Baalberge archaeological cultures but not with contemporaneous Bell Beakers. Our analyses support the existence of a common genetic signal between Western and Central Europe during the Middle and Late Neolithic and points to a heterogeneous genetic landscape among Chalcolithic groups. PMID- 25116046 TI - Efficient optical extraction of hot-carrier energy. AB - Light-induced generation of free charge carriers in semiconductors constitutes the physical basis of photodetection and photovoltaics. To maximize its efficiency, the energy of the photons must be entirely used for this purpose. This is highly challenging owing to the ultrafast thermalization of 'hot' carriers, which are created by absorption of high-energy photons. Thermalization leads to heat generation, and hence efficiency loss. To circumvent this, dedicated schemes such as photovoltaic hot-carrier cells are being explored. Here we consider optical extraction of the excess energy of hot carriers by emission of infrared photons, using erbium ions in combination with silicon nanocrystals. We determine the external quantum yield of the infrared photon generation by the erbium ions, and demonstrate that cooling of the hot carriers induces a steep, step-like, increase in erbium-related external quantum yield by up to a factor of 15 towards higher excitation energies. Finally, we comment on the potential of our findings for future photovoltaics in the form of an optical ultraviolet-to infrared spectral converter. PMID- 25116047 TI - The impact of a total hip replacement on jaw position, upper body posture and body sway. AB - OBJECTIVES: The purpose of this study was to examine whether, and to what extent, a total hip replacement can influence the position and the movement of the jaw, the upper body posture and body sway. METHODS: Twenty test subjects (6 females, 14 males) participated in this study pre- and post-total hip replacement, in addition to a healthy control group of 20 subjects (5 females, 15 males). The measurements were conducted by means of an ultrasound system to measure jaw condyle position and movement of the lower jaw, a three-dimensional back scan to analyze upper back posture, and a static and dynamic force plate to measure body sway. For statistical analysis the Wilcoxon-Matched-Pairs-Test or Man-Whitney-U Test, including a Bonferroni-Holm correction, respectively, was used. RESULTS: After surgery, the mean values of the left and right jaw condyles of the test group moved posterior, and the left condyle position was located more caudally. There were no significant differences concerning the jaw position between the two groups. There was little change in upper body posture in both groups. The test group had a more anteriorly inclined thoracic spine and a less pronounced lumbar lordosis. During static body sway measurements, increased fluctuations in the test group after surgery could be seen. CONCLUSION: Differences between both groups in the pre- and post-surgical condition could be detected. These differences were more prominent when the measured body segments were more distally located with respect to the hip region. PMID- 25116048 TI - Hemoglobin and hematocrit levels in the prediction of complicated Crohn's disease behavior--a cohort study. AB - BACKGROUND: Markers that predict the occurrence of a complicated disease behavior in patients with Crohn's disease (CD) can permit a more aggressive therapeutic regimen for patients at risk. The aim of this cohort study was to test the blood levels of hemoglobin (Hgb) and hematocrit (Hct) for the prediction of complicated CD behavior and CD related surgery in an adult patient population. METHODS: Blood samples of 62 CD patients of the German Inflammatory Bowel Disease-network "Kompetenznetz CED" were tested for the levels of Hgb and Hct prior to the occurrence of complicated disease behavior or CD related surgery. The relation of these markers and clinical events was studied using Kaplan-Meier survival analysis and adjusted COX-proportional hazard regression models. RESULTS: The median follow-up time was 55.8 months. Of the 62 CD patients without any previous complication or surgery 34% developed a complication and/or underwent CD related surgery. Low Hgb or Hct levels were independent predictors of a shorter time to occurrence of the first complication or CD related surgery. This was true for early as well as late occurring complications. Stable low Hgb or Hct during serial follow-up measurements had a higher frequency of complications compared to patients with a stable normal Hgb or Hct, respectively. CONCLUSIONS: Determination of Hgb or Hct in complication and surgery naive CD patients might serve as an additional tool for the prediction of complicated disease behavior. PMID- 25116049 TI - [Imaging of blunt chest trauma]. AB - CLINICAL/METHODOLOGICAL ISSUE: Blunt chest trauma is associated with high morbidity and mortality. Consequently, all patients should be evaluated radiologically after blunt chest trauma to allow timely and appropriate treatment. STANDARD RADIOLOGICAL METHODS: Conventional chest radiographs and computed tomography (CT) are proven modalities with which to evaluate patients after blunt chest trauma. METHODOLOGICAL INNOVATIONS: Over the last several years extended focused assessment with sonography for trauma (eFAST) has gained increasing importance for the initial assessment of seriously injured patients. PRACTICAL RECOMMENDATIONS: In the acute phase of severely injured patients eFAST examinations are helpful to exclude pneumothorax, hemothorax and hemopericardium. Chest radiographs may also be used to diagnose a pneumothorax or hemothorax; however, the sensitivity is limited and CT is the diagnostic modality of choice to evaluate severely injured patients. PMID- 25116051 TI - Periodic fluorescent silver clusters assembled by rolling circle amplification and their sensor application. AB - A simple method for preparing DNA-stabilized Ag nanoclusters (NCs) nanowires is presented. To fabricate the Ag NCs nanowires, we use just two unmodified component strands and a long enzymatically produced scaffold. These nanowires form at room temperature and have periodic sequence units that are available for fluorescence Ag NCs assembled which formed three-way junction (TWJ) structure. These Ag NCs nanowires can be clearly visualized by confocal microscopy. Furthermore, due to the high efficiency of rolling circle amplification reaction in signal amplification, the nanowires exhibit high sensitivity for the specific DNA detection with a wide linear range from 6 to 300 pM and a low detection limit of 0.84 pM, which shows good performance in the complex serum samples. Therefore, these Ag NCs nanowires might have great potential in clinical and imaging applications in the future. PMID- 25116052 TI - N-terminomics and proteogenomics, getting off to a good start. AB - Proteogenomics consists of the annotation or reannotation of protein-coding nucleic acid sequences based on the empirical observation of their gene products. While functional annotation of predicted genes is increasingly feasible given the multiplicity of genomes available for many branches of the tree of life, the accurate annotation of the translational start sites is still a point of contention. Extensive coverage of the proteome, including specifically the N termini, is now possible, thanks to next-generation mass spectrometers able to record data from thousands of proteins at once. Efforts to increase the peptide coverage of protein sequences and to detect low abundance proteins are important to make proteomic and proteogenomic studies more comprehensive. In this review, we present the panoply of N-terminus-oriented strategies that have been developed over the last decade. PMID- 25116050 TI - Dietary isoflavones and bone mineral density during midlife and the menopausal transition: cross-sectional and longitudinal results from the Study of Women's Health Across the Nation Phytoestrogen Study. AB - OBJECTIVE: This study aims to examine cross-sectional and longitudinal relations between dietary intake of isoflavones and bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in black, white, Chinese, and Japanese women during the menopausal transition. METHODS: We tested whether tertiles of isoflavone intake were associated with baseline BMD when all women were premenopausal or early perimenopausal. To analyze whether isoflavone intake was associated with longitudinal BMD, we fitted piecewise linear models to repeated measurements of baseline-normalized LS or FN BMD as functions of time before or after the final menstrual period (FMP) date. RESULTS: Multiply adjusted mean FN BMD values of premenopausal Japanese women were monotonically positively related to isoflavone consumption (P for trend = 0.0003). Otherwise, no statistically significant baseline associations were observed. During the period of 1 year before the FMP through 5 years after the FMP, all participants lost LS and FN BMD. Loss was unrelated to isoflavone intake, except for Japanese women during the period of 1 year before the FMP to 2 years after the FMP: higher tertiles of isoflavone intake were associated with greater annual LS BMD loss rates (P for trend = 0.01) and FN loss rates (P for trend = 0.04). CONCLUSIONS: In Japanese women, higher isoflavone intake is associated with higher peak FN BMD but also with greater rates of LS and FN BMD loss during the menopausal transition. Results for the other racial/ethnic groups did not support a relation between dietary intake of isoflavones and either peak BMD or BMD loss during the menopausal transition. PMID- 25116053 TI - Thermal adaptation of alpha-amylases: a review. AB - The temperature adaptation of alpha-amylase can be gained by different adjustments in protein structure with consecutive effects on the stability and flexibility of the protein. In this review, meso, thermo and cold-active alpha amylases have been compared with respect to their structure and intramolecular interactions. With decrease in temperature, the number of ionic interactions also decreases, leading to greater flexibility of proteins. It has also been observed that the proline and arginine content is higher in thermophilic amylases as compared to meso and psychrophilic amylases, increasing the rigidity and structural stability of protein molecule. PMID- 25116054 TI - The TrmB family: a versatile group of transcriptional regulators in Archaea. AB - Microbes are organisms which are well adapted to their habitat. Their survival depends on the regulation of gene expression levels in response to environmental signals. The most important step in regulation of gene expression takes place at the transcriptional level. This regulation is intriguing in Archaea because the eu-karyotic-like transcription apparatus is modulated by bacterial-like transcription regulators. The transcriptional regulator of mal operon (TrmB) family is well known as a very large group of regulators in Archaea with more than 250 members to date. One special feature of these regulators is that some of them can act as repressor, some as activator and others as both repressor and activator. This review gives a short updated overview of the TrmB family and their regulatory patterns in different Archaea as a lot of new data have been published on this topic since the last review from 2008. PMID- 25116055 TI - Acidibacter ferrireducens gen. nov., sp. nov.: an acidophilic ferric iron reducing gammaproteobacterium. AB - An acidophilic gammaproteobacterium, isolated from a pit lake at an abandoned metal mine in south-west Spain, was shown to be distantly related to all characterized prokaryotes, and to be the first representative of a novel genus and species. Isolate MCF85 is a Gram-negative, non-motile, rod-shaped mesophilic bacterium with a temperature growth optimum of 32-35 degrees C (range 8-45 degrees C). It was categorized as a moderate acidophile, growing optimally at pH 3.5-4.0 and between pH 2.5 and 4.5. Under optimum conditions its culture doubling time was around 75 min. Only organic electron donors were used by MCF85, and the isolate was confirmed to be an obligate heterotroph. It grew on a limited range of sugars (hexoses and disaccharides, though not pentoses) and some other small molecular weight organic compounds, and growth was partially or completely inhibited by small concentrations of some aliphatic acids. The acidophile grew in the presence of >100 mM ferrous iron or aluminium, but was more sensitive to some other metals, such as copper. It was also much more tolerant of arsenic (V) than arsenic (III). Isolate MCF85 catalysed the reductive dissolution of the ferric iron mineral schwertmannite when incubated under micro-aerobic or anaerobic conditions, causing the culture media pH to increase. There was no evidence, however, that the acidophile could grow by ferric iron respiration under strictly anoxic conditions. Isolate MCF85 is the designated type strain of the novel species Acidibacter ferrireducens (=DSM 27237(T) = NCCB 100460(T)). PMID- 25116056 TI - Picophytoplankton predominance in hypersaline lakes (Transylvanian Basin, Romania). AB - The occurrence and importance of photoautotrophic picoplankton (PPP, cells with a diameter <2 MUm) was studied along a trophic and salinity gradient in hypersaline lakes of the Transylvanian Basin (Romania). The studied lakes were found to be rich in PPP, with abundances (maximum 7.6 * 10(6) cells mL(-1)) higher than in freshwater and marine environments of similar trophic conditions. The contribution of PPP to the total phytoplankton biovolume did not decrease with increasing trophic state as it was generally found in other aquatic environments. Regardless of the trophic conditions, the contribution of PPP could reach 90-100 % in these hypersaline lakes. We hypothesized that the PPP predominance might be the result of the low grazing pressure, since heterotrophic nanoflagellates (the main grazers of PPP) were absent in the studied samples. There were significant differences in community composition among the lakes along the salinity gradient. CyPPP predominated in less saline waters (mainly below 5 %), while EuPPP were present along the entire salinity range (up to 18.7 %), dominating the phytoplankton between 3 and 13 % salinity. Above 13 % salinity, the phytoplankton was composed mainly of Dunaliella species. PMID- 25116057 TI - Early paternal deprivation alters levels of hippocampal brain-derived neurotrophic factor and glucocorticoid receptor and serum corticosterone and adrenocorticotropin in a sex-specific way in socially monogamous mandarin voles. AB - In monogamous mammals, fathers play an important role in the development of the brain and typical behavior in offspring, but the exact nature of this process is not well understood. In particular, little research has addressed whether the presence or absence of paternal care alters levels of hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF), and basal levels of serum corticosterone (CORT) and adrenocorticotropin (ACTH). Here, we explored this concept using socially monogamous mandarin voles (Microtus mandarinus), a species in which fathers display high levels of paternal care toward their pups. Our immunohistochemical study shows that paternal deprivation (PD) significantly decreased levels of GR and BDNF protein in the CA1 and CA2/3 of the hippocampus. In the dental gyrus, decreases in GR and BDNF induced by PD were evident in females but not in males. Additionally, enzyme-linked immunosorbent assay results show that PD significantly upregulated levels of serum CORT and ACTH in females, but not males. These findings demonstrate that PD alters HPA axis activity in a sex-specific way. The changes in stress hormones documented here may be associated with alteration in hippocampal BDNF and GR levels. PMID- 25116058 TI - Posture variation among office workers when using different information and communication technologies at work and away from work. AB - Office workers perform tasks using different information and communication technologies (ICT) involving various postures. Adequate variation in postures and muscle activity is generally believed to protect against musculoskeletal complaints, but insufficient information exists regarding the effect on postural variation of using different ICT. Thus, this study among office workers aimed to determine and compare postures and postural variation associated with using distinct types of ICT. Upper arm, head and trunk postures of 24 office workers were measured with the Physiometer over a whole day in their natural work and away-from-work environments. Postural variation was quantified using two indices: APDF(90-10) and EVA(sd). Various ICT had different postural means and variation. Paper-based tasks had more non-neutral, yet also more variable postures. Electronics-based tasks had more neutral postures, with less postural variability. Tasks simultaneously using paper- and electronics-based ICT had least neutral and least variable postures. Tasks without ICT usually had the most posture variability. Interspersing tasks involving different ICT could increase overall exposure variation among office workers and may thus contribute to musculoskeletal risk reduction. PMID- 25116064 TI - Fluorinated graphene and hexagonal boron nitride as ALD seed layers for graphene based van der Waals heterostructures. AB - Ultrathin dielectric materials prepared by atomic-layer-deposition (ALD) technology are commonly used in graphene electronics. Using the first-principles density functional theory calculations with van der Waals (vdW) interactions included, we demonstrate that single-side fluorinated graphene (SFG) and hexagonal boron nitride (h-BN) exhibit large physical adsorption energy and strong electrostatic interactions with H2O-based ALD precursors, indicating their potential as the ALD seed layer for dielectric growth on graphene. In graphene SFG vdW heterostructures, graphene is n-doped after ALD precursor adsorption on the SFG surface caused by vertical intrinsic polarization of SFG. However, graphene-h-BN vdW heterostructures help preserving the intrinsic characteristics of the underlying graphene due to in-plane intrinsic polarization of h-BN. By choosing SFG or BN as the ALD seed layer on the basis of actual device design needs, the graphene vdW heterostructures may find applications in low-dimensional electronics. PMID- 25116065 TI - [Ocular myopathies and autoimmunity]. PMID- 25116066 TI - [Clinical diagnostics for the tear film and the ocular surface]. PMID- 25116067 TI - Rectal cancer seen over 30 years. PMID- 25116072 TI - Enhanced thermal oxidation stability of reduced graphene oxide by nitrogen doping. AB - Nitrogen-doped reduced graphene oxide (N-doped RGO) samples with a high level of doping, up to 13 wt. %, have been prepared by annealing graphene oxide under a flow of pure ammonia. The presence of nitrogen within the structure of RGO induces a remarkable increase in the thermal stability against oxidation by air. The thermal stability is closely related with the temperature of synthesis and the nitrogen content. The combustion reaction of nitrogen in different coordination environments (pyridinic, pyrrolic, and graphitic) is analyzed against a graphene fragment (undoped) from a thermodynamic point of view. In agreement with the experimental observations, the combustion of undoped graphene turns out to be more spontaneous than when nitrogen atoms are present. PMID- 25116074 TI - Electro-responsively reversible transition of polythiophene films from superhydrophobicity to superhydrophilicity. AB - An electro-responsively reversible switching of wettability between superhydrophobicity and superhydrophilicity has been obtained from a highly porous structured polythiophene film. The polythiophene film was prepared by two step electrochemical deposition on an indium tin oxide (ITO) substrate. The underlying poly(3,4-ethylenedioxythiophene) (PEDOT) provides a highly porous structured conductive support, and poly(3-methylthiophene) (P(3-MTH)) deposited thereon plays the role of a low-surface-energy conductive coating. The wettability switching of this double-layer film between superhydrophobicity and superhydrophilicity has been investigated by doping and dedoping in an electrolyte solution containing ClO4(-). Electrochromism of the film was also seen to accompany the electrochemical process of conversion between the two superwetting states. On the basis of this porous electro-active film, an in situ electro-wetting device was also demonstrated. PMID- 25116073 TI - Early plasma exchange for treating ricin toxicity in children after castor bean ingestion. AB - Plasma exchange (PE) for the treatment of ricin toxicity has not been previously reported. Here we describe the use of PE to treat children who experienced ricin toxicity after ingesting castor beans. Seven children (median age: 8.1 years) who consumed castor beans (median: 5 beans) were treated with PE. All had bradycardia and sinus arrhythmia, and most had experienced episodes of vomiting and/or diarrhea. PE settings were blood flow, 50-80 mL/min; PE rate, 600-800 mL/h; volume of exchange, 1440-1950 mL. Median time from ingestion to PE was 73 h. All clinical symptoms disappeared and vital signs rapidly returned to normal after PE; no severe organ dysfunction occurred. All children were discharged and recovered uneventfully. Concentrations of all serum biochemical parameters significantly decreased immediately after PE. Some, but not all, of these parameters were also significantly decreased at 48 and 72 h after PE compared with before PE. Our findings suggest that PE can be an effective early intervention in the treatment of ricin toxicity due to castor bean ingestion. PMID- 25116075 TI - Allowing brief delays in responding improves event-based prospective memory for young adults living with HIV disease. AB - Event-based prospective memory (PM) tasks require individuals to remember to perform an action when they encounter a specific cue in the environment, and they have clear relevance for daily functioning for individuals with HIV. In many everyday tasks, not only must the individual maintain the intent to perform the PM task, but the PM task response also competes with the alternative and more habitual task response. The current study examined whether event-based PM can be improved by slowing down the pace of the task environment. Fifty-seven young adults living with HIV performed an ongoing lexical decision task while simultaneously performing a PM task of monitoring for a specific word (which was focal to the ongoing task of making lexical decisions) or syllable contained in a word (which was nonfocal). Participants were instructed to refrain from making task responses until after a tone was presented, which occurred at varying onsets (0-1600 ms) after each stimulus appeared. Improvements in focal and nonfocal PM accuracy were observed with response delays of 600 ms. Furthermore, the difference in PM accuracy between the low-demand focal PM task and the resource demanding nonfocal PM task was reduced by half across increasingly longer delays, falling from 31% at 0-ms delay to only 14% at 1600-ms delay. The degree of ongoing task response slowing for the PM conditions, relative to a control condition that did not have a PM task and made lexical decisions only, also decreased with increased delay. Overall, the evidence indicates that delaying the task responses of younger HIV-infected adults increased the probability that the PM relevant features of task stimuli were adequately assessed prior to the ongoing task response, and by implication that younger HIV infected adults can more adequately achieve PM goals when the pace of the task environment is slowed down. PMID- 25116077 TI - Inhibition of neointimal hyperplasia in rats treated with atorvastatin after carotid artery injury may be mainly associated with down-regulation of survivin and Fas expression. AB - CONTEXT: Atorvastatin is a member of the drug class known as statins, which is used for lowering blood cholesterol. OBJECTIVE: The present study investigates the effect and mechanism of atorvastatin on neointimal hyperplasia after carotid artery injury (CAI) of rat. MATERIALS AND METHODS: Fifty male rats were randomly divided into four groups: control group, sham-operated group, model group, and atorvastatin treatment group. The treatment group was fed with atorvastatin (10 mg/kg) with gastro-gavage at 5 p.m. every day for 28 d after surgery. The control group, model group, and sham-operated group were fed with the same volume of distilled water instead. The proliferations of intimal and medial layers were evaluated by hematoxylin & eosin (H&E) staining. The apoptosis of vascular smooth muscle cells (VSMCs) was determined by terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) staining. Plasma concentrations of survivin and sFas were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Atorvastatin reduced neointimal formation and increased apoptosis of VSMCs in neointima. VSMCs apoptosis emerged at 3 d (8.42 +/- 0.449 MUm) and the intimal proliferation peaked by the end of 14 d (41.58 +/- 1.64 MUm). The plasma levels of survivin and sFas were gradually increased with the neointimal hyperplasia and increasingly decreased after atorvastatin treatment. The plasma levels of survivin and sFas in rats were elevated at 3 d (464.80 +/- 105.27 pg/ml and 3256.00 +/- 478.20 pg/ml, respectively), reached the peak of survivin at 14 d (1089.20 +/- 232.32 pg/ml) and sFas at 7 d (4362.00 +/- 639.92 pg/ml) and decreased at 28 d (562.00 +/- 90.11 pg/ml and 2148.00 +/- 257.14 pg/ml, respectively) in the model group. Compared with the model group, the atorvastatin treatment group has significantly less neointimal hyperplasia and more apoptosis of VSMCs. CONCLUSIONS: Atorvastatin can inhibit neointimal hyperplasia and promote SMCs apoptosis in neointimal layers, which may be mainly associated with down-regulation of survivin and Fas expression after CAI of rat. PMID- 25116078 TI - Covalent binding of 4-hydroxynonenal to matrix metalloproteinase 13 studied by liquid chromatography-mass spectrometry. AB - Osteoarthritis (OA) is caused by the degradation of articular cartilage and affects approximately 80% of people over the age of 65. Matrix metalloproteinases (MMPs) belong to a group of zinc endopeptidases that degrade extracellular matrix (ECM) proteins in cartilage. MMP-13, also known as collagenase 3, cleaves type II collagen more rapidly than other MMPs and therefore is an important target for the treatment of OA. The lipid peroxidation product 4-hydroxy-2-(E)-nonenal (HNE), generated under oxidative stress, is known to play a crucial role in cartilage degradation; however, the mechanism is not yet fully understood. An approach has been developed to monitor HNE modification sites by incubating rhMMP 13 +/- HNE in vitro followed by analysis of tryptic digests by UHPLC coupled to high resolution (HR) quadrupole-time-of-flight (QqTOF) tandem mass spectrometry (MS/MS). The analysis elucidated several covalently modified histidine and cysteine residues. The reaction was monitored using different HNE concentrations and incubation times. A targeted assay, using multiple-reaction monitoring (MRM), was then optimized to increase the sensitivity of detecting these modification sites in biological samples. HNE-related covalent modifications of MMP-13 were confirmed in enriched extracts from interleukin 1beta-activated chondrocytes from OA patients using HR-MS/MS and MRM analysis. PMID- 25116076 TI - Exploring the influence of the protein environment on metal-binding pharmacophores. AB - The binding of a series of metal-binding pharmacophores (MBPs) related to the ligand 1-hydroxypyridine-2-(1H)-thione (1,2-HOPTO) in the active site of human carbonic anhydrase II (hCAII) has been investigated. The presence and/or position of a single methyl substituent drastically alters inhibitor potency and can result in coordination modes not observed in small-molecule model complexes. It is shown that this unexpected binding mode is the result of a steric clash between the methyl group and a highly ordered water network in the active site that is further stabilized by the formation of a hydrogen bond and favorable hydrophobic contacts. The affinity of MBPs is dependent on a large number of factors including donor atom identity, orientation, electrostatics, and van der Waals interactions. These results suggest that metal coordination by metalloenzyme inhibitors is a malleable interaction and that it is thus more appropriate to consider the metal-binding motif of these inhibitors as a pharmacophore rather than a "chelator". The rational design of inhibitors targeting metalloenzymes will benefit greatly from a deeper understanding of the interplay between the variety of forces governing the binding of MBPs to active site metal ions. PMID- 25116079 TI - Large-scale avian influenza surveillance in wild birds throughout the United States. AB - Avian influenza is a viral disease that primarily infects wild and domestic birds, but it also can be transmitted to a variety of mammals. In 2006, the United States of America Departments of Agriculture and Interior designed a large scale, interagency surveillance effort that sought to determine if highly pathogenic avian influenza viruses were present in wild bird populations within the United States of America. This program, combined with the Canadian and Mexican surveillance programs, represented the largest, coordinated wildlife disease surveillance program ever implemented. Here we analyze data from 197,885 samples that were collected from over 200 wild bird species. While the initial motivation for surveillance focused on highly pathogenic avian influenza, the scale of the data provided unprecedented information on the ecology of avian influenza viruses in the United States, avian influenza virus host associations, and avian influenza prevalence in wild birds over time. Ultimately, significant advances in our knowledge of avian influenza will depend on both large-scale surveillance efforts and on focused research studies. PMID- 25116081 TI - The impact of Universal Health Coverage on health care consumption and risky behaviours: evidence from Thailand. AB - Thailand is among the first non-OECD countries to have introduced a form of Universal Health Coverage (UHC). This policy represents a natural experiment to evaluate the effects of public health insurance on health behaviours. In this paper, we examine the impact of Thailand's UHC programme on preventive activities, unhealthy or risky behaviours and health care consumption using data from the Thai Health and Welfare Survey. We use doubly robust estimators that combine propensity scores and linear regressions to estimate differences-in differences (DD) and differences-in-DD models. Our results offer important insights. First, UHC increases individuals' likelihood of having an annual check up, especially among women. Regarding health care consumption, we observe that UHC increases hospital admissions by over 2% and increases outpatient visits by 13%. However, there is no evidence that UHC leads to an increase in unhealthy behaviours or a reduction of preventive efforts. In other words, we find no evidence of ex ante moral hazard. Overall, these findings suggest positive health impacts among the Thai population covered by UHC. PMID- 25116080 TI - Long-distance wind-dispersal of spores in a fungal plant pathogen: estimation of anisotropic dispersal kernels from an extensive field experiment. AB - Given its biological significance, determining the dispersal kernel (i.e., the distribution of dispersal distances) of spore-producing pathogens is essential. Here, we report two field experiments designed to measure disease gradients caused by sexually- and asexually-produced spores of the wind-dispersed banana plant fungus Mycosphaerella fijiensis. Gradients were measured during a single generation and over 272 traps installed up to 1000 m along eight directions radiating from a traceable source of inoculum composed of fungicide-resistant strains. We adjusted several kernels differing in the shape of their tail and tested for two types of anisotropy. Contrasting dispersal kernels were observed between the two types of spores. For sexual spores (ascospores), we characterized both a steep gradient in the first few metres in all directions and rare long distance dispersal (LDD) events up to 1000 m from the source in two directions. A heavy-tailed kernel best fitted the disease gradient. Although ascospores distributed evenly in all directions, average dispersal distance was greater in two different directions without obvious correlation with wind patterns. For asexual spores (conidia), few dispersal events occurred outside of the source plot. A gradient up to 12.5 m from the source was observed in one direction only. Accordingly, a thin-tailed kernel best fitted the disease gradient, and anisotropy in both density and distance was correlated with averaged daily wind gust. We discuss the validity of our results as well as their implications in terms of disease diffusion and management strategy. PMID- 25116082 TI - Association between interleukin-10 promoter gene polymorphisms and acute graft versus-host disease after hematopoietic stem cell transplantation: a systematic review and meta-analysis. AB - OBJECTIVES: Interleukin-10 (IL-10) is an important immunomodulatory cytokine. The association between IL-10 promoter gene polymorphisms and acute graft-versus-host disease (aGVHD) risk is established; however, results of these studies remain inconclusive. We performed a meta-analysis to clarify the effects of IL-10 promoter gene polymorphisms on aGVHD risk. METHODS: The authors searched MEDLINE, EMBASE, and Cochrane Library databases. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity. RESULTS: Finally, a total of 11 studies encompassing 3588 recipients and 3221 donors were included to study IL-10 -1082 G > A, -819 C > T, and -592 C > A polymorphisms. IL-10 -819 CC genotype was associated with an increased aGVHD risk (grade I-IV: OR, 2.722 (95% CI, 1.360-5.450); grade II-IV: OR, 2.265 (95% CI, 1.015-5.053)). Furthermore, patients who received grafts from donors with an IL-10 -819 CC genotype experienced more frequent grade I-IV aGVHD (OR, 2.306 (95% CI, 1.168-4.551)). Recipients with IL-10 -592 CC genotypes were at increased risk for grade II-IV aGVHD (OR, 1.999 (95% CI, 1.230-3.250)). Together, this meta-analysis found that IL-10 -819 CC and -592 CC polymorphisms increased aGVHD risk. DISCUSSION AND CONCLUSION: This meta-analysis found the evidence that the IL-10 -819 CC and -592 CC genotypes in both recipients and donors increased the risk of aGVHD in allogeneic hematopoietic stem cell transplantation (HSCT) patients. These results contribute towards improving patient outcome through insight and rationale for individualized treatment strategies considering genetic determinants. PMID- 25116083 TI - Production of recombinant proteins in microalgae at pilot greenhouse scale. AB - Recombinant protein production in microalgae chloroplasts can provide correctly folded proteins in significant quantities and potentially inexpensive costs compared to other heterologous protein production platforms. The best results have been achieved by using the psbA promoter and 5' untranslated region (UTR) to drive the expression of heterologous genes in a psbA-deficient, non photosynthetic, algal host. Unfortunately, using such a strategy makes the system unviable for large scale cultivation using natural sunlight for photosynthetic growth. In this study we characterized eight different combinations of 5' regulatory regions and psbA coding sequences for their ability to restore photosynthesis in a psbA-deficient Chlamydomonas reinhardtii, while maintaining robust accumulation of a commercially viable recombinant protein driven by the psbA promoter/5'UTR. The recombinant protein corresponded to bovine Milk Amyloid A (MAA), which is present in milk colostrum and could be used to prevent infectious diarrhea in mammals. This approach allowed us to identify photosynthetic strains that achieved constitutive production of MAA when grown photosynthetically in 100 L bags in a greenhouse. Under these conditions, the maximum MAA expression achieved was 1.86% of total protein, which corresponded to 3.28 mg/L of culture medium. Within our knowledge, this is the first report of a recombinant protein being produced this way in microalgae. PMID- 25116084 TI - Physical activity level and incident type 2 diabetes among Chinese adults. AB - PURPOSE: The objective is to examine the association between physical activity level (PAL) and incident type 2 diabetes among middle-age and older Chinese men and women in urban China. METHODS: This prospective study included 6348 participants (age 35 to 74 yr) who were free of diabetes and cardiovascular disease at baseline. PAL was estimated on the basis of self-reported overall physical activity on a typical day. According to PAL, participants were classified into four groups: sedentary (PAL, 1.00-1.39), low active (PAL, 1.40 1.59), active (PAL, 1.60-1.89), and very active (PAL, >1.89). The association of PAL with incident diabetes was examined by Cox proportional hazards model. RESULTS: During 7.9 yr of follow-up (50,293 person-years), 478 incident cases of type 2 diabetes were identified. After adjustment for age, sex, geographic region, educational level, smoking, alcohol use, and family history of diabetes, the HR (95% CI) values for type 2 diabetes across increasing categories of PAL were 1.00 (reference), 0.82 (0.62-1.09), 0.63 (0.47-0.83), and 0.47 (0.36-0.61), respectively (P for trend <0.0001). Additional adjustment for baseline body mass index or waist circumference attenuated the magnitude of risk reduction, but it remained significant. The inverse association between PAL and risk of incident diabetes was persistent in subgroup analyses according to age, sex, hypertension, smoking, body mass index, waist circumference, and fasting plasma glucose level. CONCLUSIONS: Higher PAL is associated with substantial reduction in risk of type 2 diabetes. Our findings suggest the importance of a physically active lifestyle in the prevention of diabetes. PMID- 25116085 TI - The effects of inspiratory muscle training in older adults. AB - PURPOSE: Declining inspiratory muscle function and structure and systemic low level inflammation and oxidative stress may contribute to morbidity and mortality during normal ageing. Therefore, we examined the effects of inspiratory muscle training (IMT) in older adults on inspiratory muscle function and structure and systemic inflammation and oxidative stress, and reexamined the reported positive effects of IMT on respiratory muscle strength, inspiratory muscle endurance, spirometry, exercise performance, physical activity levels (PAL), and quality of life (QoL). METHODS: Thirty-four healthy older adults (68 +/- 3 yr) with normal spirometry, respiratory muscle strength, and physical fitness were divided equally into a pressure-threshold IMT or sham-hypoxic placebo group. Before and after an 8-wk intervention, measurements were taken for dynamic inspiratory muscle function and inspiratory muscle endurance using a weighted plunger pressure-threshold loading device; diaphragm thickness by using B-mode ultrasonography; plasma cytokine concentrations by using immunoassays; DNA damage levels in peripheral blood mononuclear cells by using comet assays; spirometry, maximal mouth pressures, and exercise performance by using a 6-min walk test; PAL by using a questionnaire and accelerometry; and QoL using a questionnaire. RESULTS: Compared with placebo, IMT increased maximal inspiratory pressure (+34% +/- 43%, P = 0.008), diaphragm thickness at residual volume (+38% +/- 39%, P = 0.03), and peak inspiratory flow (+35% +/- 42%, P = 0.049) but did not change other spirometry measures, plasma cytokine concentrations, DNA damage levels in peripheral blood mononuclear cells, dynamic inspiratory muscle function, inspiratory muscle endurance, exercise performance, PAL, or QoL. CONCLUSION: These novel data indicate that in healthy older adults, IMT elicits some positive changes in inspiratory muscle function and structure but neither attenuates systemic inflammation and oxidative stress nor improves exercise performance, PAL, or QoL. PMID- 25116087 TI - Muscle fascicle behavior during eccentric cycling and its relation to muscle soreness. AB - A single bout of eccentric exercise confers a protective effect against muscle damage and soreness in subsequent eccentric exercise bouts, but the mechanisms underpinning this effect are unclear. PURPOSE: This study compared vastus lateralis (VL) muscle-tendon behavior between two eccentric cycling bouts to test the hypothesis that muscle-tendon behavior would be different between bouts and would be associated with the protective effect. METHODS: Eleven untrained men (27.1 +/- 7.0 yr) performed two bouts of eccentric cycling (ECC1 and ECC2) separated by 2 wk for 10 min at 65% of maximal concentric workload (191.9 +/- 44.2 W) each. Muscle soreness (by visual analog scale) and maximal voluntary isometric contraction (MVC) torque of the knee extensors were assessed before and 1-2 d after exercise. Using ultrasonography, VL fascicle length and angle changes during cycling were assessed, and tendinous tissue (TT) length changes were estimated. VL EMG amplitude, crank torque, and knee joint angles were measured during cycling. RESULTS: Soreness was greater (P < 0.0001) after ECC1 than ECC2, although MVC changes were not different between bouts (P = 0.47). No significant differences in peak EMG amplitude (normalized to EMG during MVC), crank peak torque, or knee angles were evident between bouts. However, fascicle elongation was 16% less during ECC2 than ECC1 (P < 0.01), indicating less fascicle strain in ECC2. Maximum TT length occurred at a smaller knee joint angle during ECC2 than ECC1 (P = 0.055). CONCLUSION: These results suggest that a lesser fascicle elongation and earlier TT elongation were associated with reduced muscle soreness after ECC2 than ECC1; thus, changes in muscle-tendon behavior may be an important mechanism underpinning the protective effect. PMID- 25116086 TI - Physical activity and chronic prostatitis/chronic pelvic pain syndrome. AB - PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urologic disorder among men, but its etiology is still poorly understood. Our objective was to examine the relation between physical activity and incidence of CP/CPPS in a large cohort of male health professionals. METHODS: We conducted a prospective cohort study among men in the Health Professionals Follow-up Study followed from 1986 to 2008. The study population included 20,918 men who completed all CP/CPPS questions on the 2008 questionnaire. Leisure-time physical activity, including type and intensity of activity, was measured by questionnaire in 1986. A National Institute of Health Chronic Prostatitis Symptom Index pain score was calculated on the basis of the responses on the 2008 questionnaire. Participants with pain scores >=8 were considered CP/CPPS cases (n = 689). RESULTS: Higher leisure-time physical activity was associated with lower risk of CP/CPPS. The multivariable-adjusted odds ratio comparing >35.0 to <=3.5 MET.h.wk of physical activity was 0.72 (95% confidence interval, 0.56-0.92; P for trend <0.001). Observed inverse associations between physical activity and CP/CPPS were similar for both moderate- and vigorous-intensity activities. Sedentary behavior, measured as time spent watching television, was not associated with risk of CP/CPPS (P for trend = 0.64). CONCLUSIONS: Findings from this study, the first large scale and most comprehensive study to date on this association, suggest that higher levels of leisure-time physical activity may lower risk of CP/CPPS in middle-age and older men. PMID- 25116089 TI - [Shaping demographic change]. PMID- 25116088 TI - [Paralytic ileus after ileocystoplasty in a patient with spinal cord injury: is homeopathy helpful?]. AB - A paralytic ileus is a typical complication of ileocystoplasty of the bladder. In patients with a spinal cord injury, this risk is higher due to a preexisting neurogenic bowel dysfunction. We present the case of a paraplegic man who developed a massive paralytic ileus after ileocystoplasty and surgical revision. Conventional stimulation of bowel function was unsuccessful; only by an adjunctive homeopathic treatment was normalization of bowel function achieved. Adjunctive homeopathic therapy is a promising treatment option in patients with complex bowel dysfunction after abdominal surgery who do not adequately respond to conventional treatment. PMID- 25116090 TI - The phosphoproteome of Aspergillus nidulans reveals functional association with cellular processes involved in morphology and secretion. AB - We describe the first phosphoproteome of the model filamentous fungus Aspergillus nidulans. Phosphopeptides were enriched using titanium dioxide, separated using a convenient ultra-long reverse phase gradient, and identified using a "high-high" strategy (high mass accuracy on the parent and fragment ions) with higher-energy collisional dissociation. Using this approach 1801 phosphosites, from 1637 unique phosphopeptides, were identified. Functional classification revealed phosphoproteins were overrepresented under GO categories related to fungal morphogenesis: "sites of polar growth," "vesicle mediated transport," and "cytoskeleton organization." In these same GO categories, kinase-substrate analysis of phosphoproteins revealed the majority were target substrates of CDK and CK2 kinase families, indicating these kinase families play a prominent role in fungal morphogenesis. Kinase-substrate analysis also identified 57 substrates for kinases known to regulate secretion of hydrolytic enzymes (e.g. PkaA, SchA, and An-Snf1). Altogether this data will serve as a benchmark that can be used to elucidate regulatory networks functionally associated with fungal morphogenesis and secretion. All MS data have been deposited in the ProteomeXchange with identifier PXD000715 (http://proteomecentral.proteomexchange.org/dataset/PXD000715). PMID- 25116091 TI - Halogen-free bis(imidazolium)/bis(ammonium)-di[bis(salicylato)borate] ionic liquids as energy-efficient and environmentally friendly lubricant additives. AB - Bis(imidazolium)- and bis(ammonium)-di[bis(salicylato)borate] ionic liquids with variable alkyl chain and cyclic ring structures, were synthesized and then evaluated them as potential lubricant additives. The copper strip test results revealed noncorrosive properties of these ionic liquids. Introduction of halogen content in bis(imidazolium) ionic liquid by replacement of bis(salicylato)borate (BScB) anion with hexafluorophosphate (PF6(-)), severely corroded the copper strip. Thermogravimetric results showed that bis(imidazolium) ionic liquids exhibited higher thermal stability than bis(ammonium) ionic liquids owing to compact structure provided by imidazolium rings, higher intermolecular interactions, smaller free volume and low steric hindrance. The lubrication properties of these ionic liquids as additives to synthetic lubricant poly(ethylene) glycol (PEG 200) were evaluated for steel balls. Results showed that bis(ammonium)- and bis(imidazolium)-(BScB)2 ionic liquids as additives significantly reduced both friction coefficient and wear of PEG 200. The structure of cations, particularly the variation in substituted alkyl chain length monitored the degree of reduction in friction and wear. The excellent lubrication properties were attributed to the formation of adsorbed tribo-thin film and tribochemical product during the tribo-contact. Being halogen-, phosphorus-, and sulfur-free, these ionic liquids (a) protects contact surfaces from tribo-corrosive events, (b) reduces the friction and wear, and (c) keep environment green and clean. PMID- 25116092 TI - Changing concepts of diagnostic criteria of myeloproliferative disorders and the molecular etiology and classification of myeloproliferative neoplasms: from Dameshek 1950 to Vainchenker 2005 and beyond. AB - The Polycythemia Vera Study Group (PVSG) and WHO classifications distinguished the Philadelphia (Ph(1)) chromosome-positive chronic myeloid leukemia from the Ph(1)-negative myeloproliferative neoplasms (MPN) essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (MF) or primary megakaryocytic granulocytic myeloproliferation (PMGM). Half of PVSG/WHO-defined ET patients show low serum erythropoietin levels and carry the JAK2(V617F) mutation, indicating prodromal PV. The positive predictive value of a JAK2(V617F) PCR test is 95% for the diagnosis of PV, and about 50% for ET and MF. The WHO-defined JAK2(V617F) positive ET comprises three ET phenotypes at clinical and bone marrow level when the integrated WHO and European Clinical, Molecular and Pathological (ECMP) criteria are applied: normocellular ET (WHO-ET), hypercellular ET due to increased erythropoiesis (prodromal PV) and hypercellular ET associated with megakaryocytic granulocytic myeloproliferation (EMGM). Four main molecular types of clonal MPN can be distinguished: JAK2(V617F)-positive ET and PV; JAK2 wild type ET carrying the MPL(515); mutations in the calreticulin (CALR) gene in JAK2/MPL wild-type ET and MF, and a small proportion of JAK2/MPL/CALR wild-type ET and MF patients. The JAK2(V617F) mutation load is low in heterozygous normocellular WHO-ET. The JAK2(V617F) mutation load in hetero-/homozygous PV and EMGM is clearly related to MPN disease burden in terms of splenomegaly, constitutional symptoms and fibrosis. The JAK2 wild-type ET carrying the MPL(515) mutation is featured by clustered small and giant megakaryocytes with hyperlobulated stag-horn-like nuclei, in a normocellular bone marrow (WHO-ET), and lacks features of PV. JAK2/MPL wild-type, CALR mutated hypercellular ET associated with PMGM is featured by dense clustered large immature dysmorphic megakaryocytes and bulky (cloud-like) hyperchromatic nuclei, which are never seen in WHO-ECMP-defined JAK2(V617F) mutated ET, EMGM and PV, and neither in JAK2 wild type ET carrying the MPL(515) mutation. Two thirds of JAK2/MPL wild-type ET and MF patients carry one of the CALR mutations as the cause of the third distinct MPN entity. WHO-ECMP criteria are recommended to diagnose, classify and stage the broad spectrum of MPN of various molecular etiologies. PMID- 25116093 TI - The old but new IgM Fc receptor (FcMUR). AB - IgM is the first Ig isotype to appear during phylogeny, ontogeny and the immune response. The importance of both pre-immune "natural" and antigen-induced "immune" IgM antibodies in immune responses to pathogens and self-antigens has been established by studies of mutant mice deficient in IgM secretion. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed, but fail to fully account for the IgM-mediated immune protection and regulation of immune responses. Particularly, the role of the Fc receptor for IgM (FcMUR) in such effector functions has not been explored until recently. We have identified an authentic FcMUR in humans using a functional cloning strategy and subsequently in mice by RT-PCR and describe here its salient features and the immunological consequences of FcMUR deficiency in mice. Since the FcMUR we cloned was identical to Toso or Fas inhibitory molecule 3 (FAIM3), there have been spirited debates regarding the real function of FcMUR/Toso/FAIM3 and we will also comment on this topic. PMID- 25116095 TI - Intracellular antibody immunity and the cytosolic Fc receptor TRIM21. AB - Until recently, it was thought that antibody effector mechanisms were mediated purely by Fc receptors expressed on professional cells, following capture of immune complexes in the extracellular space. Recently a new Fc receptor, TRIM21, was discovered that is expressed by cells of all histogenetic lineages and which mediates immune responses intracellularly. This new receptor possesses many unique structural and functional properties. TRIM21 binds both IgG and IgM, interacts primarily with the CH3 rather than CH2 domain and engages two heavy chains simultaneously. This latter property allows TRIM21 to bind antibodies with a higher affinity than any other Fc receptor. TRIM21 is cytosolic, has both effector and signalling functions and is exquisitely conserved in mammals. The discovery of this missing part of humoral immunity has important implications for where and how antibodies work. PMID- 25116096 TI - Computational modeling of the main signaling pathways involved in mast cell activation. AB - A global and rigorous understanding of the signaling pathways and cross regulatory processes involved in mast cell activation requires the integration of published information with novel functional datasets into a comprehensive computational model. Based on an exhaustive curation of the existing literature and using the software CellDesigner, we have built and annotated a comprehensive molecular map for the FcepsilonRI signaling network. This map can be used to visualize and interpret high-throughput expression data. Furthermore, leaning on this map and using the logical modeling software GINsim, we have derived a qualitative dynamical model, which recapitulates the most salient features of mast cell activation. The resulting logical model can be used to explore the dynamical properties of the system and its responses to different stimuli, in normal or mutant conditions. PMID- 25116097 TI - Calcium channels in Fc receptor signaling. AB - The calcium ion (Ca(2+)) is the main common second messenger involved in signaling transduction subsequent to immunoreceptor activation. Its rapid intracellular elevation induces multiple cellular responses, such as secretion, proliferation, mobility, and gene transcription. Intracellular levels of Ca(2+) need to reach a specific threshold to efficiently transduce the signal to activate transcription factors through the recruitment of Ca(2+)-binding molecules. However, since Ca(2+) cannot be metabolized, its intracellular concentration is tightly regulated to avoid the induction of programmed cell death. This highly controlled regulation of Ca(2+) homeostasis has recently been clarified by the uncovering of new ion channels. The regulation of these channels allows the role of Ca(2+) in Fc receptor transduction pathways to be more precisely defined. PMID- 25116094 TI - Emerging roles for the FCRL family members in lymphocyte biology and disease. AB - Members of the extended Fc receptor-like (FCRL) family in humans and mice are preferentially expressed by B cells and possess tyrosine-based immunoregulatory function. Although the majority of these proteins repress B cell receptor mediated activation, there is an emerging evidence for their bifunctionality and capacity to counter-regulate adaptive and innate signaling pathways. In light of these findings, the recent discovery of ligands for several of these molecules has begun to reveal exciting potential for them in normal lymphocyte biology and is launching a new phase of FCRL investigation. Importantly, these fundamental developments are also setting the stage for defining their altered roles in the pathogenesis of a growing number of immune-mediated diseases. Here we review recent advances in the FCRL field and highlight the significance of these intriguing receptors in normal and perturbed immunobiology. PMID- 25116098 TI - Regulation of FcepsilonRI signaling by lipid phosphatases. AB - Mast cells (MCs) are tissue-resident sentinels of hematopoietic origin that play a prominent role in allergic diseases. They express the high-affinity receptor for IgE (FcepsilonRI), which when cross-linked by multivalent antigens triggers the release of preformed mediators, generation of arachidonic acid metabolites, and the synthesis of cytokines and chemokines. Stimulation of the FcepsilonRI with increasing antigen concentrations follows a characteristic bell-shaped dose responses curve. At high antigen concentrations, the so-called supra-optimal conditions, repression of FcepsilonRI-induced responses is facilitated by activation and incorporation of negative signaling regulators. In this context, the SH2-containing inositol-5'-phosphatase, SHIP1, has been demonstrated to be of particular importance. SHIP1 with its catalytic and multiple protein interaction sites provides several layers of control for FcepsilonRI signaling. Regulation of SHIP1 function occurs on various levels, e.g., protein expression, receptor and membrane recruitment, competition for protein-protein interaction sites, and activating modifications enhancing the phosphatase function. Apart from FcepsilonRI-mediated signaling, SHIP1 can be activated by diverse unrelated receptor systems indicating its involvement in the regulation of antigen dependent cellular responses by autocrine feedback mechanisms or tissue-specific and/or (patho-) physiologically determined factors. Thus, pharmacologic engagement of SHIP1 may represent a beneficial strategy for patients suffering from acute or chronic inflammation or allergies. PMID- 25116099 TI - Fc receptors as adaptive immunoreceptors. AB - Most biological activities of antibodies depend on their ability to engage Receptors for the Fc portion of immunoglobulins (FcRs) on a variety of cell types. As FcRs can trigger positive and negative signals, as these signals control several biological activities in individual cells, as FcRs are expressed by many cells of hematopoietic origin, mostly of the myeloid lineage, as these cells express various combinations of FcRs, and as FcR-expressing cells have different functional repertoires, antibodies can exert a wide spectrum of biological activities. Like B and T Cell Receptors (BCRs and TCRs), FcRs are bona fide immunoreceptors. Unlike BCRs and TCRs, however, FcRs are immunoreceptors with an adaptive specificity for antigen, with an adaptive affinity for antibodies, with an adaptive structure and with an adaptive signaling. They induce adaptive biological responses that depend on their tissue distribution and on FcR-expressing cells that are selected locally by antibodies. They critically determine health and disease. They are thus exquisitely adaptive therapeutic tools. PMID- 25116100 TI - Glycosylation and Fc receptors. AB - Immunoglobulins and Fc receptors are critical glycoprotein components of the immune system. Fc receptors bind the Fc (effector) region of antibody molecules and communicate information within the innate and adaptive immune systems. Glycosylation of antibodies, particularly in the Fc region of IgG, has been extensively studied in health and disease. The N-glycans in the identical heavy chains have been shown to be critical for maintaining structural integrity, communication with the Fc receptor and the downstream immunological response. Less is known about glycosylation of the Fc receptor in either healthy or disease states, however, recent studies have implicated an active role for receptor associated oligosaccharides in the antibody-receptor interaction. Research into Fc receptor glycosylation is increasing rapidly, where Fc receptors are routinely used to analyze the binding of therapeutic monoclonal antibodies and where glycosylation of receptors expressed by cells of the immune system could potentially be used to mediate and control the differential binding of immunoglobulins. Here we discuss the glycosylation of immunoglobulin antibodies (IgA, IgE, IgG) and the Fc receptors (FcalphaR, FcepsilonR, FcgammaR, FcRn) that bind them, the function of carbohydrates in the immune response and recent advances in our understanding of these critical glycoproteins. PMID- 25116101 TI - Antibodies as natural adjuvants. AB - Antibodies in complex with specific antigen can dramatically change the antibody response to this antigen. Depending on antibody class and type of antigen, >99 % suppression or >100-fold enhancement of the response can take place. IgM and IgG3 are efficient enhancers and operate via the complement system. In contrast, IgG1, IgG2a, and IgG2b enhance antibody and CD4(+) T cell responses to protein antigens via activating Fcgamma-receptors. IgE also enhances antibody and CD4(+) T cell responses to small proteins but uses the low-affinity receptor for IgE, CD23. Most likely, IgM and IgG3 work by increasing the effective concentration of antigen on follicular dendritic cells in splenic follicles. IgG1, IgG2a, IgG2b, and IgE probably enhance antibody responses by increasing antigen presentation by dendritic cells to T helper cells. IgG antibodies of all subclasses have a dual effect, and suppress antibody responses to particulate antigens such as erythrocytes. This capacity is used in the clinic to prevent immunization of Rhesus-negative women to Rhesus-positive fetal erythrocytes acquired via transplacental hemorrage. IgG-mediated suppression in mouse models can take place in the absence of Fcgamma-receptors and complement and to date no knock-out mouse strain has been found where suppression is abrogated. PMID- 25116102 TI - IgA, IgA receptors, and their anti-inflammatory properties. AB - Immunoglobulin A (IgA) is the most abundantly produced antibody isotype in mammals. The primary function of IgA is to maintain homeostasis at mucosal surfaces and play a role in immune protection. IgA functions mainly through interaction with multiple receptors including IgA Fc receptor I (FcalphaRI), transferrin receptor 1 (CD71), asialoglycoprotein receptor (ASGPR), Fcalpha/MUR, FcRL4, and DC-SIGN/SIGNR1. In this review we discuss recent data demonstrating anti-inflammatory functions of IgA through two receptors, the FcalphaRI and DC SIGN/SIGNR1 interactions in the regulation of immunity. Serum monomeric IgA is able to mediate an inhibitory signal following the interaction with FcalphaRI. It results in partial phosphorylation of its FcRgamma-ITAM and the recruitment of the tyrosine phosphatase SHP-1, which induces cell inhibition following the formation of intracellular clusters named inhibisomes. In contrast, cross-linking of FcalphaRI by multimeric ligands induces a full phosphorylation of the FcRgamma ITAM leading to the recruitment of the tyrosine kinase Syk and cell activation. In addition, secretory IgA can mediate a potent anti-inflammatory function following the sugar-dependent interaction with SIGNR1 on dendritic cells which induces an immune tolerance via regulatory T cell expansion. Overall, the anti inflammatory effect of serum and secretory IgA plays a crucial role in the physiology and in the prevention of tissue damage in multiple autoimmune and inflammatory diseases. PMID- 25116103 TI - humanized mice to study FcgammaR function. AB - Passive immunotherapy represents a promising therapeutic intervention for a number of neoplastic, chronic inflammatory, and infectious diseases, with several monoclonal antibodies currently under development or already in use in the clinic. While Fab-antigen interactions play a crucial role in the activity of an antibody, it has become clear that Fc-mediated effector functions are involved during antibody-mediated activities in vivo. A complete understanding of the contributions of effector activities mediated by an antibody during its in vivo function is required for the development of antibodies with improved therapeutic efficacies. Animal models that are commonly used for the preclinical evaluation of antibodies include murine and non-human primate species, whose FcgammaRs present substantial structural, functional, and genetic variation compared with their human counterparts. Therefore, the use of such animal models provides limited information on the role of human IgG Fc-FcgammaR interactions during the in vivo activities of antibodies intended for human therapeutics. In this chapter, we describe the development and evaluation of an FcgammaR-humanized mouse model for the study of human FcgammaR function in vivo. In this model, endogenous mouse FcgammaR genes have been deleted and human FcgammaRs are expressed as transgenes that faithfully recapitulate the unique pattern of human FcgammaR expression. Evaluation of the in vivo activities of a number of cytotoxic or therapeutic antibodies using FcgammaR-humanized mice provided useful insights into human IgG Fc effector function. This mouse model has become a vital preclinical model for testing therapeutic human antibodies to treat malignancies, autoimmunity, inflammation, and infectious disease. PMID- 25116104 TI - FcRn: from molecular interactions to regulation of IgG pharmacokinetics and functions. AB - The neonatal Fc receptor, FcRn, is related to MHC class I with respect to its structure and association with beta2microglobulin (beta2m). However, by contrast with MHC class I molecules, FcRn does not bind to peptides, but interacts with the Fc portion of IgGs and belongs to the Fc receptor family. Unlike the 'classical' Fc receptors, however, the primary functions of FcRn include salvage of IgG (and albumin) from lysosomal degradation through the recycling and transcytosis of IgG within cells. The characteristic feature of FcRn is pH dependent binding to IgG, with relatively strong binding at acidic pH (<6.5) and negligible binding at physiological pH (7.3-7.4). FcRn is expressed in many different cell types, and endothelial and hematopoietic cells are the dominant cell types involved in IgG homeostasis in vivo. FcRn also delivers IgG across cellular barriers to sites of pathogen encounter and consequently plays a role in protection against infections, in addition to regulating renal filtration and immune complex-mediated antigen presentation. Further, FcRn has been targeted to develop both IgGs with extended half-lives and FcRn inhibitors that can lower endogenous antibody levels. These approaches have implications for the development of longer lived therapeutics and the removal of pathogenic or deleterious antibodies. PMID- 25116106 TI - Bridging autoantibodies and arthritis: the role of Fc receptors. AB - Autoantibodies represent a hallmark of Rheumatoid arthritis (RA), which is a chronic inflammatory autoimmune disease characterized by inflammation and damage in the joints. Anti-Citrullinated Protein Antibodies (ACPA) are the most prominent autoantibodies present in RA patients. These autoantibodies have been intensively investigated during the last 20 years due to their diagnostic and predictive value. Furthermore, they are believed to be involved in mediating the damage associated with RA. Antibodies of the IgG isotype interact with the immune system via Fcgamma receptors expressed on immune cells as well as nonimmune cells. These receptors, therefore, form the bridge between Fcgamma receptor positive cells and antibodies complexed to antigen allowing the modulation and activation of cellular immune responses that are involved in immune defense against invading microorganisms. However, in case triggered by antibodies against self-antigens, they can also play a pivotal role in the induction and perpetuation of autoimmune diseases such as RA. Mouse models have been indispensably important for understanding the role of Fcgamma receptors in the development of arthritis. Here we discuss the contribution of autoantibodies to the pathogenesis of arthritis in preclinical animal models, as well as RA, in relation to their interaction with the different (immune inhibitory and activating) Fcgamma receptors. PMID- 25116107 TI - The FcgammaR of humans and non-human primates and their interaction with IgG: implications for induction of inflammation, resistance to infection and the use of therapeutic monoclonal antibodies. AB - Considerable effort has focused on the roles of the individual members of the FcgammaR receptor (FcgammaR) family in inflammatory diseases and humoral immunity. Recent work has revealed major roles in infection and in particular HIV pathogenesis and immunity. In addition, FcgammaR functions underpin the action of many of the successful therapeutic monoclonal antibodies. This emphasises the need for a greater understanding of FcgammaR function in humans and in the NHP which provides a key model for human immunity and preclinical testing of antibodies. We discuss recent key aspects of the human FcgammaR receptor biology and structure to define differences and similarities in activity between the human and macaque Fc receptors. These differences and similarities nuance the interpretation of infection and vaccine studies in the macaque. Indeed passive IgG antibody protection in lentivirus infection models in the macaque provided early evidence for the role of Fc receptors in anti-HIV immunity that have subsequently gained support from human vaccine trials. None-the-less the diverse functions and cellular contexts of FcgammaR receptor expression ensure there is much still to understand of the protective and deleterious effects of FcgammaRs in HIV infection. Careful comparative studies of human and non-human primate FcgammaRs will facilitate our appreciation of what attributes of HIV specific IgG antibodies, either acquired naturally or via vaccination, are most important for protection. PMID- 25116108 TI - FcgammaRIIB as a key determinant of agonistic antibody efficacy. AB - Fc gamma Receptor (FcgammaR) IIB (CD32B) is an immunoreceptor tyrosine inhibitory motif (ITIM)-bearing Fc receptor that is involved in abrogating the signalling and function delivered from other receptors; archetypally those arising from other, activatory, FcgammaR and from the B cell receptor (BCR) for antigen. In the context of immunotherapy, it has convincingly been shown to limit a variety of clinically important therapeutic monoclonal antibodies (mAb) such as rituximab and trastuzumab in preclinical models. However, recent exploration of so-called immunomodulatory mAb, for example agonist mAb directed against various members of the TNFR super-family, has cast new light on the ability of FcgammaRIIB to regulate immune responses and immunotherapy. These data, accumulated by several independent groups, have shown the seemingly paradoxical ability of FcgammaRIIB to augment or even be absolutely required for the activity of this class of mAb. In this review we highlight the key role of FcgammaRIIB in regulating agonistic mAb, detail the likely mechanism of action and propose new ways in which this information may be exploited therapeutically. PMID- 25116109 TI - Fc receptor-dependent mechanisms of monoclonal antibody therapy of cancer. AB - Targeted therapies like treatment with monoclonal antibodies (mAbs) have entered the arsenal of modern anticancer drugs. mAbs combine specificity with multiple effector functions that can lead to reduction of tumour burden. Direct mechanisms of action, including induction of apoptosis or growth inhibition, depend on the biology of the target antigen. Fc tails of mAbs have furthermore the potential to initiate complement-dependent lysis as well as immune effector cell-mediated tumour cell killing via binding to Fc receptors. Natural killer cells can induce apoptosis via antibody-dependent cellular cytotoxicity (ADCC), whereas macrophages are able to phagocytose mAb-opsonized tumour cells (antibody dependent cellular phagocytosis; ADCP). Finally, neutrophils can induce non apoptotic tumour cell death, especially in the presence of immunoglobulin A (IgA) antitumour mAbs. In spite of promising clinical successes in some malignancies, improvement of mAb immunotherapy is required to achieve overall complete remission in cancer patients. New strategies to enhance Fc receptor-mediated mechanisms of action or to overcome the immunosuppressive microenvironment of the tumour in mAb therapy of cancer are therefore currently being explored and will be addressed in this chapter. PMID- 25116110 TI - Sweet and sour: the role of glycosylation for the anti-inflammatory activity of immunoglobulin G. AB - The importance of immunoglobulin G (IgG) molecules for providing long-term sterile immunity as well as their major contribution to tissue inflammation during autoimmune diseases is generally accepted. In a similar manner, studies over the last years have elucidated many details of the molecular and cellular pathways underlying this protective activity in vivo, emphasizing the role of cellular recognizing the constant antibody fragment. In contrast, the active anti inflammatory activity of IgG, despite being known and actually identified in human autoimmune patients more than 30 years ago, is much less defined. Recent evidence from several independent model systems suggests that IgG glycosylation is critical for the immunomodulatory activity of IgG and that both monomeric IgG as well as IgG immune complexes can diminish Fc receptor and complement dependent inflammatory processes. Moreover, there is increasing evidence that IgG molecules also modulate B and T cell responses, which may suggest that IgG is centrally involved in the establishment and maintenance of immune homeostasis. PMID- 25116111 TI - High aspect ratio nano-fabrication of photonic crystal structures on glass wafers using chrome as hard mask. AB - Wafer-scale nano-fabrication of silicon nitride (Si x N y ) photonic crystal (PhC) structures on glass (quartz) substrates is demonstrated using a thin (30 nm) chromium (Cr) layer as the hard mask for transferring the electron beam lithography (EBL) defined resist patterns. The use of the thin Cr layer not only solves the charging effect during the EBL on the insulating substrate, but also facilitates high aspect ratio PhCs by acting as a hard mask while deep etching into the Si x N y . A very high aspect ratio of 10:1 on a 60 nm wide grating structure has been achieved while preserving the quality of the flat top of the narrow lines. The presented nano-fabrication method provides PhC structures necessary for a high quality optical response. Finally, we fabricated a refractive index based PhC sensor which shows a sensitivity of 185 nm per RIU. PMID- 25116105 TI - Human FcR polymorphism and disease. AB - Fc receptors play a central role in maintaining the homeostatic balance in the immune system. Our knowledge of the structure and function of these receptors and their naturally occurring polymorphisms, including single nucleotide polymorphisms and/or copy number variations, continues to expand. Through studies of their impact on human biology and clinical phenotype, the contributions of these variants to the pathogenesis, progression, and/or treatment outcome of many diseases that involve immunoglobulin have become evident. They affect susceptibility to bacterial and viral pathogens, constitute as risk factors for IgG or IgE mediated inflammatory diseases, and impact the development of many autoimmune conditions. In this chapter, we will provide an overview of these genetic variations in classical FcgammaRs, FcRLs, and other Fc receptors, as well as challenges in achieving an accurate and comprehensive understanding of the FcR polymorphisms and genomic architecture. PMID- 25116116 TI - Effects of foot placement, hand positioning, age and climbing biodynamics on ladder slip outcomes. AB - Ladder falls frequently cause severe injuries; yet the factors that influence ladder slips/falls are not well understood. This study aimed to quantify (1) the effects of restricted foot placement, hand positioning, climbing direction and age on slip outcomes, and (2) differences in climbing styles leading to slips versus styles leading to non-slips. Thirty-two occupational ladder users from three age groups (18-24, 25-44 and 45-64 years) were unexpectedly slipped climbing a vertical ladder, while being assigned to different foot placement conditions (unrestricted vs. restricted toe clearance) and different hand positions (rails vs. rungs). Constraining foot placement increased the climber's likelihood of slipping (p < 0.01), while younger and older participants slipped more than the middle-aged group (p < 0.01). Longer double stance time, dissimilar and more variable foot and body positioning were found in styles leading to a slip. Maintaining sufficient toe clearance and targeting ladder safety training to younger and older workers may reduce ladder falls. Practitioner Summary: Ladder falls frequently cause severe occupational fall injuries. This study aims to identify safer ladder climbing techniques and individuals at risk of falling. The results suggest that ladders with unrestricted toe clearance and ladder climbing training programmes, particularly for younger and older workers, may reduce ladder slipping risk. PMID- 25116117 TI - Erythroidine alkaloids: a novel class of phytoestrogens. AB - Erythrina poeppigiana is a medicinal plant which is widely used in Asia, Latin America, and Africa in traditional remedies for gynecological complications and maladies. In continuation of studies for the discovery of novel phytoestrogens, four erythroidine alkaloids, namely alpha-erythroidine, beta-erythroidine, and their oxo-derivatives 8-oxo-alpha-erythroidine and 8-oxo-beta-erythroidine, were isolated and structurally characterized from the methanolic extract of the stem bark of E. poeppigiana. Due to the high amounts of erythroidines in the extract and considering the widespread utilization of Erythrina preparations in traditional medicine, the exploration of their estrogenic properties was performed. The estrogenicity of the isolated erythroidines was assayed in various estrogen receptor-(ER)-dependent test systems, including receptor binding affinity, cell culture based ER-dependent reporter gene assays, and gene expression studies in cultured cells using reverse transcription polymerase chain reaction techniques. alpha-Erythroidine and beta-erythroidine showed binding affinity values for ERalpha of 0.015 +/- 0.010% and 0.005 +/- 0.010%, respectively, whereas only beta-erythroidine bound to ERbeta (0.006 +/- 0.010%). In reporter gene assays, both erythroidines exhibited a significant dose dependent estrogenic stimulation of ER-dependent reporter gene activity in osteosarcoma cells detectable already at 10 nM. Results were confirmed in the MVLN cells, a bioluminescent variant of MCF-7 breast cancer cells. Further, alpha erythroidine and beta-erythroidine both induced the enhanced expression of the specific ERalpha-dependent genes trefoil factor-1 and serum/glucocorticoid regulated kinase 3 in MCF-7 cells, confirming estrogenicity. Additionally, using molecular docking simulations, a potential mode of binding on ERalpha, is proposed, supporting the experimental evidences. This is the first time that an estrogenic profile is reported for erythroidine alkaloids, potentially a new class of phytoestrogens. PMID- 25116118 TI - Ruscogenin protects against high-fat diet-induced nonalcoholic steatohepatitis in hamsters. AB - The protective effects of ruscogenin on nonalcoholic steatohepatitis in hamsters fed a high-fat diet were investigated. Ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) was orally administered by gavage once daily for eight weeks. A high-fat diet induced increases in plasma levels of total cholesterol, triglycerides, and free fatty acids, while the degree of insulin resistance was lowered by ruscogenin. High-fat diet-induced hepatic steatosis and necroinflammation were improved by ruscogenin. Gene expression of inflammatory cytokines and activity of nuclear transcription factor-kappaB were also increased in the high-fat diet group, which were attenuted by ruscogenin. Ruscogenin decreased hepatic mRNA levels of sterol regulatory element-binding protein-1c and its lipogenic target genes. The hepatic mRNA expression of peroxisome proliferator-activated receptor alpha, together with its target genes responsible for fatty acid beta-oxidation were upregulated by ruscogenin. In conclusion, these findings suggest that ruscogenin may attenuate high-fat diet-induced steatohepatitis through anti-inflammatory mechanisms, reducing hepatic lipogenic gene expression, and upregulating proteins in the fatty acid oxidation process. PMID- 25116119 TI - Transport in Caco-2 cell monolayers of antidiabetic cucurbitane triterpenoids from Momordica charantia fruits. AB - Bitter melon, the fruit of Momordica charantia L. (Cucurbitaceae), is a widely used treatment for diabetes in traditional medicine systems throughout the world. Various compounds have been shown to be responsible for this reputed activity, and, in particular, cucurbitane triterpenoids are thought to play a significant role. The objective of this study was to investigate the gastrointestinal transport of a triterpenoid-enriched n-butanol extract of M. charantia using a two-compartment transwell human intestinal epithelial cell Caco-2 monolayer system, simulating the intestinal barrier. Eleven triterpenoids in this extract were transported from the apical to basolateral direction across Caco-2 cell monolayers, and were identified or tentatively identified by HPLC-TOF-MS. Cucurbitane triterpenoids permeated to the basolateral side with apparent permeability coefficient (P app) values for 3-beta-7-beta,25-trihydroxycucurbita 5,23(E)-dien-19-al and momordicines I and II at 9.02 * 10(-6), 8.12 * 10(-6), and 1.68 * 10(-6)cm/s, respectively. Also, small amounts of these triterpenoids were absorbed inside the Caco-2 cells. This is the first report of the transport of the reputed antidiabetic cucurbitane triterpenoids in human intestinal epithelial cell monolayers. Our findings, therefore, further support the hypothesis that cucurbitane triterpenoids from bitter melon may explain, at least in part, the antidiabetic activity of this plant in vivo. PMID- 25116120 TI - Vermistatin derivatives with alpha-glucosidase inhibitory activity from the mangrove endophytic fungus Penicillium sp. HN29-3B1. AB - Three new vermistatin derivatives, 6-demethylpenisimplicissin (1), 5' hydroxypenisimplicissin (2), and 2''-epihydroxydihydrovermistatin (3), along with five known vermistatin analogues, methoxyvermistatin (4), vermistatin (5), 6 demethylvermistatin (6), hydroxyvermistatin (7), and penisimplicissin (8), were isolated from the culture of the mangrove endophytic fungus Penicillium sp. HN29 3B1 from Cerbera manghas. Their structures were elucidated mainly by nuclear magnetic resonance spectroscopy. The absolute configurations of compounds 1 and 2 were deduced on the basis of circular dichroism data. The absolute structures of compounds 3 and 5 were confirmed by a single-crystal X-ray diffraction experiment using Cu Kalpha radiation. In the bioactivity assay, compounds 1 and 3 exhibited alpha-glucosidase inhibitory activity with IC50 values of 9.5 +/- 1.2 and 8.0 +/- 1.5 uM, respectively. The plausible biosynthetic pathways for all compounds are discussed. PMID- 25116121 TI - Extralevator abdominoperineal resection--a video vignette. PMID- 25116122 TI - Hypoglycaemic role of wheatgrass and its effect on carbohydrate metabolic enzymes in type II diabetic rats. AB - Diabetes mellitus (DM) is a leading cause of morbidity and mortality in the world. Insulin resistance and insulin insufficiency is the major factor for the prognosis of type II diabetes. Consistent high glucose level leads to multiple secondary complications in diabetic patients. Hence, hypoglycaemic drugs are of significance for reducing the risk of secondary complications in type II diabetes. Various hypoglycaemic drugs are already available in the market, but they are associated with several side effects. Therefore, traditional herbs have emerged as safer alternative for effective hypoglycaemic treatment. The juvenile grass of common wheat is known as wheatgrass (WG). It is commonly used as a health drink and has potent antioxidant efficacy. It has been used to cure DM in folk medicine. The current study was planned to test the hypoglycaemic effect and pathways regulated by WG on DM. We analysed the glucose and insulin levels in plasma, the activity of glucose oxidative enzymes, hexokinase and glucose 6 phosphate dehydrogenase, in serum and glycogen levels in liver of the male albino Wistar rats. Activity of glucose oxidative enzymes and the levels of insulin and liver glycogen were decreased in rats with diabetes, but they were reversed on treatment with WG. Hence, we conclude that WG can act as a potent anti hyperglycaemic agent. PMID- 25116123 TI - Catalytic formation of acrylate from carbon dioxide and ethene. AB - With regard to sustainability, carbon dioxide (CO2) is an attractive C1 building block. However, due to thermodynamic restrictions, reactions incorporating CO2 are relatively limited so far. One of the so-called "dream reactions" in this field is the catalytic oxidative coupling of CO2 and ethene and subsequent beta-H elimination to form acrylic acid. This reaction has been studied intensely for decades. However up to this date no suitable catalytic process has been established. Here we show that the catalytic conversion of ethene and CO2 to acrylate is possible in the presence of a homogeneous nickel catalyst in combination with a "hard" Lewis acid. For the first time, catalytic conversion of CO2 and ethene to acrylate with turnover numbers (TON) of up to 21 was demonstrated. PMID- 25116126 TI - The use of plasma exchange in Hashimoto's encephalopathy: A case report and review of the literature. AB - Hashimoto's Encephalopathy (HE) is a very rare condition characterized by psychosis, seizures, cognitive fluctuations, and myoclonus. In a few published cases, plasma exchange has been used due to the theoretical removal of antithyroid peroxidase antibodies (anti-TPO), one of the postulated causes of the condition. We report a case of HE treated by plasma exchange where no clinical or neurophysiologic improvement was observed despite documented reduction of the anti-TPO antibody to levels below the limits of laboratory detection. We discuss these findings in the context of the known literature for this disease process. PMID- 25116125 TI - Celastrol inhibits lung infiltration in differential syndrome animal models by reducing TNF-alpha and ICAM-1 levels while preserving differentiation in ATRA induced acute promyelocytic leukemia cells. AB - All-trans retinoic acid (ATRA) is a revolutionary agent for acute promyelocytic leukemia (APL) treatment via differentiation induction. However, ATRA treatment also increases cytokine, chemokine, and adhesive molecule (mainly ICAM-1) expression, which can cause clinical complications, including a severe situation known as differentiation syndrome (DS) which can cause death. Therefore, it is of clinical significance to find a strategy to specifically blunt inflammatory effects while preserving differentiation. Here we report that the natural compound, celastrol, could effectively block lung infiltrations in DS animal models created by loading ATRA-induced APL cell line NB4. In ATRA-treated NB4 cells, celastrol could potently inhibit ICAM-1 elevation and partially reduce TNF alpha and IL-1beta secretion, though treatment showed no effects on IL-8 and MCP 1 levels. Celastrol's effect on ICAM-1 in ATRA-treated NB4 was related to reducing MEK1/ERK1 activation. Strikingly and encouragingly, celastrol showed no obvious effects on ATRA-induced NB4 differentiation, as determined by morphology, enzymes, and surface markers. Our results show that celastrol is a promising and unique agent for managing the side effects of ATRA application on APL, and suggest that hyper-inflammatory ability is accompanied by, but not necessary for, APL differentiation. Thus we offered an encouraging novel strategy to further improve differentiation therapy. PMID- 25116128 TI - Improved electrical performance and bias stability of solution-processed active bilayer structure of indium zinc oxide based TFT. AB - We fabricated active single- and bilayer structure thin film transistors (TFTs) with aluminum or gallium doped (IZO:Al or IZO:Ga) and undoped indium zinc oxide (IZO) thin film layers using an aqueous solution process. The electrical performance and bias stability of these active single- and bilayer structure TFTs were investigated and compared to reveal the effects of Al/Gal doping and bilayer structure. The single-layer structure IZO TFT shows a high mobility of 19 cm(2)/V . s with a poor positive bias stability (PBS) of DeltaVT + 3.4 V. However, Al/Ga doped in IZO TFT reduced mobility to 8.5-9.9 cm(2)/V . s but improved PBS to DeltaVT + 1.6-1.7 V due to the reduction of oxygen vacancy. Thus, it is found the bilayer structure TFTs with a combination of bottom- and top-layer compositions modify both the mobility and bias stability of the TFTs to be optimized. The bilayer structure TFT with an IZO:X bottom layer possess high mobility and an IZO bottom layer improves the PBS. PMID- 25116127 TI - Second generation inactivated eastern equine encephalitis virus vaccine candidates protect mice against a lethal aerosol challenge. AB - Currently, there are no FDA-licensed vaccines or therapeutics for eastern equine encephalitis virus (EEEV) for human use. We recently developed several methods to inactivate CVEV1219, a chimeric live-attenuated eastern equine encephalitis virus (EEEV). Dosage and schedule studies were conducted to evaluate the immunogenicity and protective efficacy of three potential second-generation inactivated EEEV (iEEEV) vaccine candidates in mice: formalin-inactivated CVEV1219 (fCVEV1219), INA-inactivated CVEV1219 (iCVEV1219) and gamma-irradiated CVEV1219 (gCVEV1219). Both fCVEV1219 and gCVEV1219 provided partial to complete protection against an aerosol challenge when administered by different routes and schedules at various doses, while iCVEV1219 was unable to provide substantial protection against an aerosol challenge by any route, dose, or schedule tested. When evaluating antibody responses, neutralizing antibody, not virus specific IgG or IgA, was the best correlate of protection. The results of these studies suggest that both fCVEV1219 and gCVEV1219 should be evaluated further and considered for advancement as potential second-generation inactivated vaccine candidates for EEEV. PMID- 25116129 TI - Neurocognitive moderation of associations between cannabis use and psychoneuroticism. AB - BACKGROUND: Cannabis use has been associated with neurocognitive impairments and psychopathology. The strength of such associations does however appear to depend on many different factors, such as duration and intensity of use, but also differential susceptibility due to genetic make-up and environmental influences. The present study investigated whether specific cognitive weaknesses moderated associations between cannabis use and psychoneuroticism, which may be considered one of the "softer" expressions of an extended psychosis phenotype. METHOD: One hundred and fifty (150) young adults (mean age: 24.7 years, SD: 3.7), mostly college students, performed three computerized neuropsychological tasks: a relatively easy social perception task (Face Recognition), a more complex social perception task combining emotion recognition and executive functioning (Matching Facial Emotions), and a more complex task requiring sustained attention and executive functioning (Sustained Attention-Dots). Participants self-reported on the extent to which they experienced psychological problems using the Symptom Checklist-90 (SCL-90). The SCL-90 total score (psychoneuroticism) was used as dependent variable in analyses of variance. RESULTS: Frequent and current cannabis users performed more poorly than nonusers on the three tasks. They also reported more psychoneuroticism than nonusers whether they were classified according to their lifetime use, their use during the past 12 months, or use during the past 4 weeks. Moderate and former users did not differ from nonusers. Relatively poor performance on the Matching Facial Emotions task, as opposed to performance on the Face Recognition and Sustained Attention tasks, augmented levels of experienced psychoneuroticism among frequent and current cannabis users. CONCLUSIONS: Relatively poor cognitive abilities appear to represent increased vulnerability to effects of frequent and current cannabis use on affective mental health, even among highly educated individuals. There seems to be some specificity as to which (combinations of) neurocognitive abilities may be most indicative, as moderating effects were only observed when participants had relatively poor complex social perception ability. PMID- 25116130 TI - Directed arene/alkyne annulation reactions via aerobic copper catalysis. AB - We describe a straightforward protocol for a smooth dehydrogenative annulation reaction between various arenes and terminal alkynes using a catalytic amount of CuBr2 and molecular oxygen. 3-Methyleneisoindoline derivatives are prepared in high yields. PMID- 25116131 TI - The prognostic value of the hawkins sign and diagnostic value of MRI after talar neck fractures. AB - BACKGROUND: The early diagnosis of avascular necrosis of the talus (AVN) and prediction of ankle function for talar fractures are important. The Hawkins sign, as a radiographic predictor, could exclude the possibility of developing ischemic bone necrosis after talar neck fractures, but its relationship with ankle function remains unclear. The purpose of this study was to illustrate the prognostic effect of the Hawkins sign on ankle function after talar neck fractures and to study the value of early MRI in detecting the AVN changes after talus fractures. METHODS: Cases of talar neck fractures between November 2008 and November 2013 were evaluated. The occurrences of the Hawkins sign and AVN were studied. X-ray imaging was performed at multiple time points from the 4th to the 12th week after the fractures, and MRI examinations were used in the Hawkins sign negative group, with the time span ranging from 1.5 to 12 months. AOFAS scores of the Hawkins sign positive and negative groups were compared during the follow-up. Forty-four cases (48 feet) were evaluated. RESULTS: The occurrence of positive Hawkins sign was 50%, 30%, and 33.3%, the incidence of AVN was 0%, 10%, and 50%, respectively, in type I, type II, and type III and IV talus fractures, respectively. The AOFAS scores showed no statistically significant difference between Hawkins sign positive group and negative group in type I and II fractures. The Hawkins sign positive group had better AOFAS scores than the negative group in type III and IV fractures. However, there was no statistically significant difference between Hawkins sign positive and negative groups when AVN cases were excluded in type III and IV fractures. CONCLUSION: The Hawkins sign was a reliable predictor excluding the possibility of AVN. It did not have predictive value on the ankle function in low-energy fractures and may predict better ankle function in high-energy fractures. MRI can diagnose AVN during an earlier period, and we believe Hawkins sign negative patients should undergo MRI examinations 12 weeks after the fractures, especially in high-energy traumatic cases. LEVEL OF EVIDENCE: Level III, comparative case series. PMID- 25116132 TI - Comparison of continuous nerve block versus patient-controlled analgesia for postoperative pain and outcome after talar and calcaneal fractures. AB - BACKGROUND: Talar and calcaneal fractures and their treatment can cause severe postoperative pain. We hypothesized that a continuous peripheral nerve block (CPNB) would reduce pain scores more effectively than systemic analgesics, improve recovery, and lead to reduced length of stay (LOS). METHODS: Over a 3 year period patients undergoing open reduction and internal fixation (ORIF) of a talar or calcaneal fracture were retrospectively analyzed. Patients received a CPNB catheter preoperatively or intravenous patient-controlled analgesia (PCA) postoperatively. Primary endpoint was Numerical Rating Scale (NRS) scores on postoperative day 1. Secondary endpoints were NRS scores up to day 3, opioid requirement, analgesia-related side effects, intraoperative blood loss, infection, and LOS. Eighty-seven patients were analyzed; 70 with calcaneal fracture, 21 with talar fracture, 4 with both. In all, 40 patients received CPNB, 47 patients PCA. RESULTS: Median NRS scores on day 1 were 1.0 (IQR 3) in the CPNB group and 2.0 (IQR 3) in the PCA group (ns). Median LOS for patients with CPNB was 5 days (IQR3) and PCA 4 days (IQR 2 ns). Blood loss and incidence of local infections were comparable in both groups. Opioid requirement was significantly increased in the PCA group (P < .01). CONCLUSION: Significant advantages or disadvantages were not seen in either group. However, the PCA group required about 30-fold more opioids compared to the CPNB group on day 1, although that did not lead to an increased number of side effects. LEVEL OF EVIDENCE: Level III, retrospective comparative series. PMID- 25116133 TI - Changing aetiology of healthcare-associated bloodstream infections at three medical centres in Taiwan, 2000-2011. AB - This multicentre surveillance study was conducted to investigate the trends in incidence and aetiology of healthcare-associated bloodstream infections (HCA BSIs) in Taiwan. From 2000 to 2011 a total of 56 830 HCA-BSIs were recorded at three medical centres, and coagulase-negative staphylococci (CoNS) were the most common pathogens isolated (n = 9465, 16.7%), followed by E. coli (n = 7599, 13.4%). The incidence of all HCA-BSIs in each and all hospitals significantly increased over the study period owing to the increase of aerobic Gram-positive cocci and Enterobacteriaceae by 4.2% and 3.6%, respectively. Non-fermenting Gram negative bacteria, Bacteroides spp. and Candida spp. also showed an increase but there was a significant decline in the numbers of methicillin-resistant S. aureus. In conclusion, the incidence of HCA-BSIs in Taiwan is significantly increasing, especially for Enterobacteriaceae and aerobic Gram-positive cocci. PMID- 25116134 TI - Spectrum of diseases diagnosed on bone marrow examination of 285 infants in a single tertiary care center. AB - OBJECTIVES: Bone marrow (BM) aspiration and trephine biopsy is one of the most valuable procedures in the evaluation of hematological disorders. There is a shortage of published literature regarding the indications, procedure, and outcome of bone marrow examination (BME) in neonates and infants. The aim of the present study is to analyze the common indications of performing BME and to assess the spectrum of disorders diagnosed from BM of neonates and infants. METHODS: A retrospective analysis of BMEs performed in infants over a period of 5 years, between 2009 and 2013 was done. RESULTS AND DISCUSSION: A total of 297 BME were performed on 285 infants, which constitutes 10.3% of pediatric BME procedures during the same period. In our institute, BME is routinely performed by trained pathologists from posterior superior iliac spine in children including infants and neonates with an overall sample adequacy of 97%. Evaluation of cytopenias and suspicion of storage disorder were the most common indications for BME procedure, while acute leukemias and storage disorders were the most common diagnoses offered in infant BM. CONCLUSIONS: Posterior superior iliac spine is a good site of BME in neonates and infants. BM trephine biopsy is a difficult procedure in this age group, however remains indispensable in situations where an infiltrative pathology is suspected. BME not only helps to make specific diagnoses but should also be used as an extremely valuable, quick, and economically viable procedure to exclude major hematological disorders including certain forms of storage disorder and hematological malignancy in this age group. PMID- 25116135 TI - Saccharomyces cerevisiae Sen1 as a model for the study of mutations in human Senataxin that elicit cerebellar ataxia. AB - The nuclear RNA and DNA helicase Sen1 is essential in the yeast Saccharomyces cerevisiae and is required for efficient termination of RNA polymerase II transcription of many short noncoding RNA genes. However, the mechanism of Sen1 function is not understood. We created a plasmid-based genetic system to study yeast Sen1 in vivo. Using this system, we show that (1) the minimal essential region of Sen1 corresponds to the helicase domain and one of two flanking nuclear localization sequences; (2) a previously isolated terminator readthrough mutation in the Sen1 helicase domain, E1597K, is rescued by a second mutation designed to restore a salt bridge within the first RecA domain; and (3) the human ortholog of yeast Sen1, Senataxin, cannot functionally replace Sen1 in yeast. Guided by sequence homology between the conserved helicase domains of Sen1 and Senataxin, we tested the effects of 13 missense mutations that cosegregate with the inherited disorder ataxia with oculomotor apraxia type 2 on Sen1 function. Ten of the disease mutations resulted in transcription readthrough of at least one of three Sen1-dependent termination elements tested. Our genetic system will facilitate the further investigation of structure-function relationships in yeast Sen1 and its orthologs. PMID- 25116136 TI - Genetic analysis of resistance and sensitivity to 2-deoxyglucose in Saccharomyces cerevisiae. AB - Aerobic glycolysis is a metabolic pathway utilized by human cancer cells and also by yeast cells when they ferment glucose to ethanol. Both cancer cells and yeast cells are inhibited by the presence of low concentrations of 2-deoxyglucose (2DG). Genetic screens in yeast used resistance to 2-deoxyglucose to identify a small set of genes that function in regulating glucose metabolism. A recent high throughput screen for 2-deoxyglucose resistance identified a much larger set of seemingly unrelated genes. Here, we demonstrate that these newly identified genes do not in fact confer significant resistance to 2-deoxyglucose. Further, we show that the relative toxicity of 2-deoxyglucose is carbon source dependent, as is the resistance conferred by gene deletions. Snf1 kinase, the AMP-activated protein kinase of yeast, is required for 2-deoxyglucose resistance in cells growing on glucose. Mutations in the SNF1 gene that reduce kinase activity render cells hypersensitive to 2-deoxyglucose, while an activating mutation in SNF1 confers 2-deoxyglucose resistance. Snf1 kinase activated by 2-deoxyglucose does not phosphorylate the Mig1 protein, a known Snf1 substrate during glucose limitation. Thus, different stimuli elicit distinct responses from the Snf1 kinase. PMID- 25116138 TI - Adsorption of enzyme onto lignins of liquid hot water pretreated hardwoods. AB - The adsorption of cellulase enzymes onto lignin is shown to be non-productive and therefore reduces enzymatic hydrolysis of liquid hot water pretreated cellulose. Among the enzyme components of Trichoderma reesei cellulase cocktail, beta glucosidase showed the strongest adsorption onto lignin. Only 2-18% of the initial beta-glucosidase activity remained in the supernatant while 50-60% of cellobiohydrolase and endoglucanase activities were recovered after incubation with lignin. By increasing the pH to 5.5 and adding NaCl to a 200 mM, the free enzymes in the supernatant were increased but hydrolysis was not enhanced since optimal pH for enzymatic hydrolysis is at 4.8. Electrostatic interactions contributed to enzyme adsorption and their effect was most pronounced for T. reesei beta-glucosidase which had high molecular weights (78-94 kDa) and high isoelectric points (pI 5.7-6.4). Since the enzyme components which are required to synergistically hydrolyze cellulose have different profiles (molecular weight, hydrophobicity and pI), they exhibit different adsorption behaviors with lignin, and thereby change the ratio of enzyme activities needed for synergism during cellulose hydrolysis. beta-glucosidase from Aspergillus niger exhibits less adsorption than beta-glucosidase from T. reesei. Supplemental addition of A. niger beta-glucosidase to the enzyme mixture increases hydrolysis of pretreated hardwood by a factor of two. The analysis presented in this paper shows that lignins with higher guaiacyl content adsorb more cellulase enzymes, particularly beta-glucosidase, and that adsorption of beta-glucosidase onto lignin indirectly suppresses enzymatic hydrolysis of cellulose in pretreated hardwoods due to decreased hydrolysis of cellobiose which in turn accumulates and inhibits CBH. PMID- 25116137 TI - The conserved PFT1 tandem repeat is crucial for proper flowering in Arabidopsis thaliana. AB - It is widely appreciated that short tandem repeat (STR) variation underlies substantial phenotypic variation in organisms. Some propose that the high mutation rates of STRs in functional genomic regions facilitate evolutionary adaptation. Despite their high mutation rate, some STRs show little to no variation in populations. One such STR occurs in the Arabidopsis thaliana gene PFT1 (MED25), where it encodes an interrupted polyglutamine tract. Although the PFT1 STR is large (~270 bp), and thus expected to be extremely variable, it shows only minuscule variation across A. thaliana strains. We hypothesized that the PFT1 STR is under selective constraint, due to previously undescribed roles in PFT1 function. We investigated this hypothesis using plants expressing transgenic PFT1 constructs with either an endogenous STR or synthetic STRs of varying length. Transgenic plants carrying the endogenous PFT1 STR generally performed best in complementing a pft1 null mutant across adult PFT1-dependent traits. In stark contrast, transgenic plants carrying a PFT1 transgene lacking the STR phenocopied a pft1 loss-of-function mutant for flowering time phenotypes and were generally hypomorphic for other traits, establishing the functional importance of this domain. Transgenic plants carrying various synthetic constructs occupied the phenotypic space between wild-type and pft1 loss-of-function mutants. By varying PFT1 STR length, we discovered that PFT1 can act as either an activator or repressor of flowering in a photoperiod-dependent manner. We conclude that the PFT1 STR is constrained to its approximate wild-type length by its various functional requirements. Our study implies that there is strong selection on STRs not only to generate allelic diversity, but also to maintain certain lengths pursuant to optimal molecular function. PMID- 25116139 TI - Neural circuits: putting a stop to feeding. PMID- 25116140 TI - Fly visual course control: behaviour, algorithms and circuits. AB - Understanding how the brain controls behaviour is undisputedly one of the grand goals of neuroscience research, and the pursuit of this goal has a long tradition in insect neuroscience. However, appropriate techniques were lacking for a long time. Recent advances in genetic and recording techniques now allow the participation of identified neurons in the execution of specific behaviours to be interrogated. By focusing on fly visual course control, I highlight what has been learned about the neuronal circuit modules that control visual guidance in Drosophila melanogaster through the use of these techniques. PMID- 25116142 TI - Synaptic plasticity: a homeostatic messenger. PMID- 25116143 TI - Chemically stable and mechanically durable superamphiphobic aluminum surface with a micro/nanoscale binary structure. AB - We developed a simple fabrication method to prepare a superamphiphobic aluminum surface. On the basis of a low-energy surface and the combination of micro- and nanoscale roughness, the resultant surface became super-repellent toward a wide range of liquids with surface tensions of 25.3-72.1 mN m(-1). The applied approach involved (1) the formation of an irregular microplateau structure on an aluminum surface, (2) the fabrication of a nanoplatelet structure, and (3) fluorination treatment. The chemical stability and mechanical durability of the superamphiphobic surface were evaluated in detail. The results demonstrated that the surface presented an excellent chemical stability toward cool corrosive liquids (HCl/NaOH solutions, 25 degrees C) and 98% concentrated sulfuric acid, hot liquids (water, HCl/NaOH solutions, 30-100 degrees C), solvent immersion, high temperature, and a long-term period. More importantly, the surface also exhibited robust mechanical durability and could withstand multiple-fold, finger touch, intensive scratching by a sharp blade, ultrasonication treatment, boiling treatment in water and coffee, repeated peeling by adhesive tape, and even multiple abrasion tests under 500 g of force without losing superamphiphobicity. The as-prepared superamphiphobic surface was also demonstrated to have excellent corrosion resistance. This work provides a simple, cost-effective, and highly efficient method to fabricate a chemically stable and mechanically robust superamphiphobic aluminum surface, which can find important outdoor applications. PMID- 25116141 TI - Localized GABAergic inhibition of dendritic Ca(2+) signalling. AB - Neuronal circuits are defined by synaptic connections between their cellular constituents. In this article, I highlight several recent studies emphasizing the surprising level of precision exhibited by inhibitory GABAergic synapses within the neocortex and hippocampus. Specifically, GABAergic inputs to dendritic shafts and spines of pyramidal cells have a key role in the localized regulation of neuronal Ca(2+) signalling. These findings provide important new insights into the cellular mechanisms underlying the contributions of inhibitory transmission to both normal and abnormal brain activity. PMID- 25116144 TI - Metaproteomics: Evaluation of protein extraction from activated sludge. AB - Metaproteomic studies of full-scale activated sludge systems require reproducible protein extraction methods. A systematic evaluation of three different extractions protocols, each in combination with three different methods of cell lysis, and a commercial kit were evaluated. Criteria used for comparison of each method included the extracted protein concentration and the number of identified proteins and peptides as well as their phylogenetic, cell localization and functional distribution and quantitative reproducibility. Furthermore, the advantage of using specific metagenomes and a 2-step database approach was illustrated. The results recommend a protocol for protein extraction from activated sludge based on the protein extraction reagent B-Per and bead beating. The data have been deposited to the ProteomeXchange with identifier PXD000862 (http://proteomecentral.proteomexchange.org/dataset/PXD000862). PMID- 25116145 TI - Timing the ischaemic stroke by 1H-MRI: improved accuracy using absolute relaxation times over signal intensities. AB - One in four ischaemic stroke patients are ineligible for thrombolytic treatment due to unknown onset time. Quantification of absolute MR relaxation times and signal intensities are potential methods for estimating stroke duration. We compared the accuracy of these approaches and determined whether changes in relaxation times and signal intensities identify the same ischaemic tissue as diffusion MRI. Seven Wistar rats underwent permanent middle cerebral artery occlusion to induce focal ischaemia and were scanned at six time points. The trace of the diffusion tensor (DAV), T1rho and T2 were acquired at 4.7 T. Results show relaxation times, and signal intensities of the MR relaxation parameters increase linearly with ischaemia duration (P<0.001). Using T1rho and T2 relaxation times, an estimate of 4.5 h after occlusion has an uncertainty of +/- 12 and +/- 35 min, respectively, compared with over 50 min for signal intensities. In addition, we present a pixel-by-pixel method that simultaneously estimates stroke onset time and identifies potentially irreversible ischaemic tissue using absolute relaxation times. This method demonstrates signal intensity changes during ischaemia display an ambiguous pattern and highlights the possibility that diffusion MRI overestimates the true extent of irreversible ischaemia. In conclusion, quantification of absolute relaxation times at a single time point enables a more accurate estimation of stroke duration than signal intensities and provides more information about tissue status in ischaemia. PMID- 25116147 TI - Oxidation of nanopores in a silicon membrane: self-limiting formation of sub-10 nm circular openings. AB - We describe a simple but reliable approach to shrink silicon nanopores with nanometer precision for potential high throughput biomolecular sensing and parallel DNA sequencing. Here, nanopore arrays on silicon membranes were fabricated by a self-limiting shrinkage of inverted pyramidal pores using dry thermal oxidation at 850 degrees C. The shrinkage rate of the pores with various initial sizes saturated after 4 h of oxidation. In the saturation regime, the shrinkage rate is within +/- 2 nm h(-1). Oxidized pores with an average diameter of 32 nm were obtained with perfect circular shape. By careful design of the initial pore size, nanopores with diameters as small as 8 nm have been observed. Statistics of the pore width show that the shrinkage process did not broaden the pore size distribution; in most cases the distribution even decreased slightly. The progression of the oxidation and the deformation of the oxide around the pores were characterized by focused ion beam and electron microscopy. Cross sectional imaging of the pores suggests that the initial inverted pyramidal geometry is most likely the determining factor for the self-limiting shrinkage. PMID- 25116146 TI - A simple repeat polymorphism in the MITF-M promoter is a key regulator of white spotting in dogs. AB - The white spotting locus (S) in dogs is colocalized with the MITF (microphtalmia associated transcription factor) gene. The phenotypic effects of the four S alleles range from solid colour (S) to extreme white spotting (s(w)). We have investigated four candidate mutations associated with the s(w) allele, a SINE insertion, a SNP at a conserved site and a simple repeat polymorphism all associated with the MITF-M promoter as well as a 12 base pair deletion in exon 1B. The variants associated with white spotting at all four loci were also found among wolves and we conclude that none of these could be a sole causal mutation, at least not for extreme white spotting. We propose that the three canine white spotting alleles are not caused by three independent mutations but represent haplotype effects due to different combinations of causal polymorphisms. The simple repeat polymorphism showed extensive diversity both in dogs and wolves, and allele-sharing was common between wolves and white spotted dogs but was non existent between solid and spotted dogs as well as between wolves and solid dogs. This finding was unexpected as Solid is assumed to be the wild-type allele. The data indicate that the simple repeat polymorphism has been a target for selection during dog domestication and breed formation. We also evaluated the significance of the three MITF-M associated polymorphisms with a Luciferase assay, and found conclusive evidence that the simple repeat polymorphism affects promoter activity. Three alleles associated with white spotting gave consistently lower promoter activity compared with the allele associated with solid colour. We propose that the simple repeat polymorphism affects cooperativity between transcription factors binding on either flanking sides of the repeat. Thus, both genetic and functional evidence show that the simple repeat polymorphism is a key regulator of white spotting in dogs. PMID- 25116148 TI - Characterisation and mapping of gene Lr73 conferring seedling resistance to Puccinia triticina in common wheat. AB - KEY MESSAGE: A gene conferring seedling resistance to Puccinia triticina was mapped to chromosome 2BS in the wheat Morocco. The gene was shown to be distinct and was therefore designated Lr73. The wheat genotype Morocco, widely susceptible to isolates of Puccinia triticina, was resistant to an Australian isolate of this pathogen collected in 2004. Genetic studies established that the resistance in Morocco was also present the Australian wheat genotypes Avocet, Halberd, Harrier, Tincurrin and a selection of cultivar Warigal lacking the resistance gene Lr20. Genetic studies based on a cross with Halberd showed that the gene is dominant and located on chromosome 2BS (XwPt8760-4 cM-Lr73-1.4 cM-XwPt8235). The gene was genetically independent of the Lr13, Lr16 and Lr23 loci, also located on chromosome 2BS, indicating that it is distinct. The locus designation Lr73 was therefore assigned. On the basis of multi-pathotype tests, it is likely Lr73 is also present in the Australian wheat cultivars Clearfield STL, Federation (with Lr10), Gatcher (with Lr10 and Lr27+Lr31), Marombi (with Lr1 and Lr37), Pugsley (with Lr1 and Lr37), Spear (with Lr1), Stiletto and Tarsa (with Lr1). Gene Lr73 is unlikely to be of value in resistance breeding. However, recognising Lr73 is important to avoid its inadvertent selection in breeding programmes. Furthermore, the apparent rarity of avirulence for genes like Lr73, sometimes referred to as "fossil" resistance genes, makes them of interest in terms of the evolution of disease resistance in host plants and of virulence in the respective rust pathogens. PMID- 25116149 TI - Synthetic food colours in saffron solutions, saffron rice and saffron chicken from restaurants in Tehran, Iran. AB - Saffron solutions, saffron rice and saffron chicken samples were considered for synthetic colours as additives, which are forbidden according to Iranian national standards. Samples were taken from restaurants of three locations and analysed by high-performance liquid chromatography. Of the total 573 samples, 52% were positive for at least one colour. The most prevalent colours were Tartrazine, Quinoline Yellow and Sunset Yellow, with 44%, 9.1% and 8.4% of the samples testing positive for these colours, respectively. Carmoisine and Ponceau were both detected only in 0.5% of the positive samples and found only in saffron solution. In conclusion, synthetic food colours, especially Tartrazine should be regarded as a potential risk in saffron and its related food. Therefore, new attempts for food safety and quality should be undertaken to eliminate the use of these colours in restaurants. PMID- 25116150 TI - Spectroscopic and quantum mechanical investigation of N,N'-bisarylmalonamides: solvent and structural effects. AB - The UV absorption spectra of ten N,N'-bisarylmalonamides have been recorded in the range 200-400 nm in a set of selected solvents. The solute-solvent interactions have been analyzed on the basis of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The effects of substituents on the absorption spectra have been interpreted by correlating absorption frequencies with Hammett substituent constants. Furthermore, the experimental findings have been interpreted using the DFT CAM-B3LYP/6-311+G(d,p) method. Electronic energies have been calculated using the same method in combination with the implicit solvation model (conductor-like polarizable continuum model, CPCM) as well as with the explicit addition of two molecules of solvent. PMID- 25116151 TI - Investigation of the torsional barrier of EDOT using molecular mechanics and DFT methods. AB - When heterocyclic monomers are polymerized by electrochemical or chemical methods, they form fully conjugated polymers which have a wide range of applications due to their outstanding electronic properties. Among this class of compounds, thiophene derivatives are widely used due to their chemical stability and synthesis flexibility. With the goal to investigate the torsion barrier of polymer chains, a few units of 3,4-ethylenedioxythiophene (EDOT) were chosen and submitted to molecular mechanics (MM), density functional theory (DFT) and coupled cluster CCSD(T) calculations. This study helps to understand the performance and transferability of force fields used in molecular mechanics and molecular dynamics simulations often used to describe structure-property relationships of those systems. Determination of inter-ring torsion angle was performed in a comparative study using both force field, DFT and CCSD(T) methods. A good agreement was noticed between MM and QC results and highlights the importance of the description of the interactions involving the oxygen atoms present in the structure of EDOT. These observations are related to the alpha,alpha-coupling that occurs between the monomer units and yields a linear polymer. DFT HOMO and LUMO orbitals were also presented. Finally, UV-vis spectra of EDOT units were obtained using several levels of theory by means of time dependent DFT calculations (TD-DFT). PMID- 25116153 TI - Deformation density and energy decomposition to describe interactions between (eta5-C5H5)M and highly reactive molecules C4H4 and (C3H3)-. AB - Using DFT calculations, an energy decomposition analysis (EDA) combined with natural orbitals for chemical valence (NOCV), EDA-NOCV approach was used to describe the nature of the interaction between eta5-cyclopentadienyl metal complexes (eta5-C5H5)M, with M=Co, Rh, and cyclobutadiene (Cb) and cyclopropenyl anion (C3H3)- molecules, which are highly reactive molecules in their free state. EDA-NOCV draws a covalent picture for these interactions. With this interpretation of interactions, the character of aromaticity could be the result of the delocalization of six electrons in pi orbitals of the (eta5-C5H5)M fragment and Cb/C3H3(-1) ligand. This description of the bonding interaction might also justify the experimental observation that, in complexes of CpM-Cb (M=Co, Rh), the viability of the Friedel-Crafts acylation and other electrophilic substitutions on the four-membered ring is greater than that of the five-membered ring. PMID- 25116152 TI - Computational approaches for evaluating the effect of sequence variations and the intrinsically disordered C-terminal region of the Helicobacter pylori CagA protein on the interaction with tyrosine kinase Src. AB - The Helicobacter pylori CagA protein was the first bacterial oncoprotein to be identified as important in the development of human malignancies such as gastric cancer. It is not clear how it is able to deregulate a set of cell control mechanisms to induce carcinogenesis following translocation into human gastric epithelial cells. It is likely, however, that structural variations in the CagA sequence alter its affinity with the host proteins inducing differences in the pathogenicity of different H. pylori strains. Using the recently elucidated N terminal 3D structure of H. pylori CagA, information on the full cagA gene sequence, and intrinsically disordered protein structure predictions methods we evaluated the interaction of different CagA variants with the kinase Src. An automated docking followed by molecular dynamics simulations were performed to explore CagA interaction modes with Src, one of its cellular partners. The computational approach let us establish that even in the presence of the same number and type of EPIYA motifs, CagA protein can reveal different spatial distributions. Based on the lowest affinity energy and higher number of interactions it was established that the principal forces governing the CagA-Src interaction are electrostatic. Results showed that EPIYA-D models presents higher affinity with some host proteins than EPIYA-C. Thus, we highlight the importance and advantage of the use of computational tools in combining chemical and biological data with bioinformatics for modeling and prediction purposes in some cases where experimental techniques present limitations. PMID- 25116158 TI - Laparoscopic repair of recurrent incisional hernia using a 'balloon' for mesh positioning--a video vignette. PMID- 25116159 TI - Essential differences in clinical and bone marrow features in BCR/ABL-positive thrombocythemia compared to thrombocythemia in the BCR/ABL-negative myeloproliferative neoplasms essential thrombocythemia and polycythemia vera. PMID- 25116160 TI - [Compliance with treatment in bronchial asthma - supply in everyday conditions of pulmonology practice. Pneumology 2014; 68: 315-321 Supply of asthma patients with combination therapy of ICS and LABA - a SHI data analysis. Pneumology 2014; 68: 336-343]. PMID- 25116162 TI - Synthesis and characterization of Ag8(Ge1-x,Snx )(S6-y ,Sey) colloidal nanocrystals. AB - A facile colloidal approach to synthesize Ag8 (Ge1-x ,Snx )(S6-y ,Sey ) nanocrystals (NCs) in a highly controlled way across the entire compositional ranges (0<=x<=1, 0<=y<=6) has been developed. The NCs exhibit a uniform size distribution, highly crystalline structure, over 1 g scalable synthesis, and tunable band gaps in the range of 0.88-1.45 eV by varying their chemical compositions. The Ag8 GeS6 NCs with a band gap of approximately 1.45 eV were employed as a model light harvester to assess their applicability in solar cells by a full solution-processing device, yielding an efficiency of 0.28 % under AM1.5 illumination, demonstrating their application potential in solar energy utilization. PMID- 25116161 TI - The genetic basis of variation in clean lineages of Saccharomyces cerevisiae in response to stresses encountered during bioethanol fermentations. AB - Saccharomyces cerevisiae is the micro-organism of choice for the conversion of monomeric sugars into bioethanol. Industrial bioethanol fermentations are intrinsically stressful environments for yeast and the adaptive protective response varies between strain backgrounds. With the aim of identifying quantitative trait loci (QTL's) that regulate phenotypic variation, linkage analysis on six F1 crosses from four highly divergent clean lineages of S. cerevisiae was performed. Segregants from each cross were assessed for tolerance to a range of stresses encountered during industrial bioethanol fermentations. Tolerance levels within populations of F1 segregants to stress conditions differed and displayed transgressive variation. Linkage analysis resulted in the identification of QTL's for tolerance to weak acid and osmotic stress. We tested candidate genes within loci identified by QTL using reciprocal hemizygosity analysis to ascertain their contribution to the observed phenotypic variation; this approach validated a gene (COX20) for weak acid stress and a gene (RCK2) for osmotic stress. Hemizygous transformants with a sensitive phenotype carried a COX20 allele from a weak acid sensitive parent with an alteration in its protein coding compared with other S. cerevisiae strains. RCK2 alleles reveal peptide differences between parental strains and the importance of these changes is currently being ascertained. PMID- 25116164 TI - Limb apraxia and verb processing in Alzheimer's disease. AB - OBJECTIVE: The present research investigates language and praxis abilities in patients with Alzheimer's disease in order to study the relationship between these two cognitive domains. METHOD: The experimental evaluation of patients and control group performance was designed to permit a direct comparison of linguistic abilities (i.e., verb and noun naming and sentence comprehension) and praxic abilities (i.e., gesture execution for complex movements). Moreover, for the first time, action comprehension was explored using the Action Sequence Comprehension. RESULTS AND CONCLUSION: Analyses of variance (ANOVAs) and correlational analyses showed that a direct relationship may exist between language impairment and apraxia in patients with Alzheimer's disease. In addition, the production and comprehension of both language and action were equally impaired in patients, providing further evidence for a spectrum of concomitant linguistic and praxis deficits in Alzheimer's disease. Finally, the ability to correctly comprehend action semantics was related more directly to verb production ability than to noun production. PMID- 25116165 TI - Pre-B-cell acute lymphoblastic leukemia in a boy with hereditary multiple exostoses caused by EXT1 deletion. PMID- 25116163 TI - NRPquest: Coupling Mass Spectrometry and Genome Mining for Nonribosomal Peptide Discovery. AB - Nonribosomal peptides (NRPs) such as vancomycin and daptomycin are among the most effective antibiotics. While NRPs are biomedically important, the computational techniques for sequencing these peptides are still in their infancy. The recent emergence of mass spectrometry techniques for NRP analysis (capable of sequencing an NRP from small amounts of nonpurified material) revealed an enormous diversity of NRPs. However, as many NRPs have nonlinear structure (e.g., cyclic or branched cyclic peptides), the standard de novo sequencing tools (developed for linear peptides) are not applicable to NRP analysis. Here, we introduce the first NRP identification algorithm, NRPquest, that performs mutation-tolerant and modification-tolerant searches of spectral data sets against a database of putative NRPs. In contrast to previous studies aimed at NRP discovery (that usually report very few NRPs), NRPquest revealed nearly a hundred NRPs (including unknown variants of previously known peptides) in a single study. This result indicates that NRPquest can potentially make MS-based NRP identification as robust as the identification of linear peptides in traditional proteomics. PMID- 25116166 TI - The Last Bastion of Sexual and Gender Prejudice? Sexualities, Race, Gender, Religiosity, and Spirituality in the Examination of Prejudice Toward Sexual and Gender Minorities. AB - Prior research has reported that many Americans hold prejudicial attitudes toward sexual and gender minorities. Most of this research analyzed attitudes toward target categories in isolation and not in relation to attitudes toward heterosexuals. In addition, most previous research has not examined attitudes of members of sexual and gender minority categories toward other categories. While some research has examined the influence of religiosity on attitudes toward sexual and gender minorities, none of these studies has examined religiosity while also examining the influence of spirituality. In this article we drew on insights from queer theory to examine attitudes toward heterosexual, gay, lesbian, bisexual, and transgender individuals, as well as individuals who practice polygamy, among college students. Three samples gathered over a four year period (2009, 2011, 2013) at a private, nonsectarian, midsized urban university in the Southeastern United States were used. We found that heterosexuals had the most positive rating, followed in order of rating by gay/lesbian, bisexual, and transgender individuals, and then those who practice polygamy. Regression analyses revealed gender and race were significant predictors of attitudes toward various sexual and gender categories. Holding a literalistic view of the Bible and self-identifying as more religious were related to more negative views toward sexual minorities, while self-identifying as more spiritual was related to more positive views. PMID- 25116167 TI - Lymphaticovenular anastomosis to prevent cellulitis associated with lymphoedema. AB - BACKGROUND: One of the complications of lymphoedema is recurrent cellulitis. The aim was to determine whether lymphaticovenous anastomosis (LVA) was effective at reducing cellulitis in patients with lymphoedema. METHODS: This was a retrospective review of patients with arm/leg lymphoedema who underwent LVA. The frequency of cellulitis was compared before and after surgery. The diagnostic criteria for cellulitis were a fever of 38.5 degrees C or higher, and warmth/redness in the affected limb(s). RESULTS: A total of 95 patients were included. The mean number of episodes of cellulitis in the year preceding surgery was 1.46, compared with 0.18 in the year after surgery (P < 0.001). CONCLUSION: LVA reduced the rate of cellulitis in these patients with lymphoedema. PMID- 25116169 TI - Acute pancreatitis. PMID- 25116171 TI - Synthesis and electrochemical performance of surface-modified nano-sized core/shell tin particles for lithium ion batteries. AB - Tin is able to lithiate and delithiate reversibly with a high theoretical specific capacity, which makes it a promising candidate to supersede graphite as the state-of-the-art negative electrode material in lithium ion battery technology. Nevertheless, it still suffers from poor cycling stability and high irreversible capacities. In this contribution, we show the synthesis of three different nano-sized core/shell-type particles with crystalline tin cores and different amorphous surface shells consisting of SnOx and organic polymers. The spherical size and the surface shell can be tailored by adjusting the synthesis temperature and the polymer reagents in the synthesis, respectively. We determine the influence of the surface modifications with respect to the electrochemical performance and characterize the morphology, structure, and thermal properties of the nano-sized tin particles by means of high-resolution transmission electron microscopy, x-ray diffraction, and thermogravimetric analysis. The electrochemical performance is investigated by constant current charge/discharge cycling as well as cyclic voltammetry. PMID- 25116170 TI - Differential and conditional activation of PKC-isoforms dictates cardiac adaptation during physiological to pathological hypertrophy. AB - A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-delta was significantly induced during pathological hypertrophy while PKC-alpha was exclusively activated during physiological hypertrophy in our study. PKC-delta activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-alpha during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-delta and simultaneous inhibition of phospho-PKC-alpha resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-alpha and -delta have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation. PMID- 25116173 TI - Facile immobilization of ag nanocluster on nanofibrous membrane for oil/water separation. AB - Superhydrophobic and superoleophilic electrospun nanofibrous membranes exhibiting excellent oil/water separation performance were green fabricated by a facile route combining the amination of electrospun polyacrylonitrile (APAN) nanofibers and immobilization of a Ag nanocluster with an electroless plating technique, followed by n-hexadecyl mercaptan (RSH) surface modification. By introducing the hierarchically rough structures and low surface energy, the pristine superhydrophilic APAN nanofibrous membranes could be endowed with a superhydrophobicity with water contact angle of 171.1 +/- 2.3 degrees , a superoleophilicity with oil contact angle of 0 degrees and a self-cleaning surface arising from the extremely low water contact angle hysteresis (3.0 +/- 0.6 degrees ) and a low water-adhesion property. Surface morphology studies have indicated that the selective wettability of the resultant membranes could be manipulated by tuning the electroless plating time as well as the hierarchical structures. More importantly, the extremely high liquid entry pressure of water (LEPw, 175 +/- 3 kPa) and the robust fiber morphology of the APAN immobilized Ag nanocluster endowed the as-prepared membranes with excellent separation capability and stability for oil/water separation by a solely gravity-driven process. The resultant membranes exhibited remarkable separation efficiency in both hyper-saline environment and broad pH range conditions, as well as excellent recyclability, which would make them a promising candidate for industrial oil contaminated water treatments and marine spilt oil cleanup, and provided a new prospect to achieve functional nanofibrous membranes for oil/water separation. PMID- 25116172 TI - Synergistic effect of Aspergillus niger and Trichoderma reesei enzyme sets on the saccharification of wheat straw and sugarcane bagasse. AB - Plant-degrading enzymes can be produced by fungi on abundantly available low-cost plant biomass. However, enzymes sets after growth on complex substrates need to be better understood, especially with emphasis on differences between fungal species and the influence of inhibitory compounds in plant substrates, such as monosaccharides. In this study, Aspergillus niger and Trichoderma reesei were evaluated for the production of enzyme sets after growth on two "second generation" substrates: wheat straw (WS) and sugarcane bagasse (SCB). A. niger and T. reesei produced different sets of (hemi-)cellulolytic enzymes after growth on WS and SCB. This was reflected in an overall strong synergistic effect in releasing sugars during saccharification using A. niger and T. reesei enzyme sets. T. reesei produced less hydrolytic enzymes after growth on non-washed SCB. The sensitivity to non-washed plant substrates was not reduced by using CreA/Cre1 mutants of T. reesei and A. niger with a defective carbon catabolite repression. The importance of removing monosaccharides for producing enzymes was further underlined by the decrease in hydrolytic activities with increased glucose concentrations in WS media. This study showed the importance of removing monosaccharides from the enzyme production media and combining T. reesei and A. niger enzyme sets to improve plant biomass saccharification. PMID- 25116174 TI - Fumonisins B1 and B2 in maize harvested in Hebei province, China, during 2011 2013. AB - A total of 125 maize kernel samples were collected from Hebei province in China during 2011-2013 and were analysed for incidence and contamination levels of fumonisins (FB1 + FB2) by HPLC with fluorescence detection. The incidence of FBs for all samples was 46.4%. The mean contamination level of FBs for the samples collected in 2013 was 706 MUg kg-1, which was higher than the levels in 2012 (429 MUg kg-1) and 2011 (250 MUg kg-1). All samples, except five, exhibited total FB levels below 4000 MUg kg-1, which is the maximum limit as set by the European Commission. The probable daily intakes of FBs (0.04 in 2011; 0.07 in 2012; 0.12 in 2013, expressed as MUg kg-1 body weight/day) were all within the provisional maximum tolerable daily intake of 2.0 MUg kg-1 of body weight/day as set by the Joint FAO/WHO Expert Committee on Food Additives. Nevertheless, monitoring is needed to prevent and control the potential risk of FB exposure to the consumers. PMID- 25116180 TI - Laparoscopic anterior resection in a patient with situs inversus--a video vignette. PMID- 25116181 TI - [Decreasing dementia incidence rates? Implications for public health and prevention]. PMID- 25116175 TI - The coactivator PGC-1alpha regulates skeletal muscle oxidative metabolism independently of the nuclear receptor PPARbeta/delta in sedentary mice fed a regular chow diet. AB - AIMS/HYPOTHESIS: Physical activity improves oxidative capacity and exerts therapeutic beneficial effects, particularly in the context of metabolic diseases. The peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha (PGC-1alpha) and the nuclear receptor PPARbeta/delta have both been independently discovered to play a pivotal role in the regulation of oxidative metabolism in skeletal muscle, though their interdependence remains unclear. Hence, our aim was to determine the functional interaction between these two factors in mouse skeletal muscle in vivo. METHODS: Adult male control mice, PGC 1alpha muscle-specific transgenic (mTg) mice, PPARbeta/delta muscle-specific knockout (mKO) mice and the combination PPARbeta/delta mKO + PGC-1alpha mTg mice were studied under basal conditions and following PPARbeta/delta agonist administration and acute exercise. Whole-body metabolism was assessed by indirect calorimetry and blood analysis, while magnetic resonance was used to measure body composition. Quantitative PCR and western blot were used to determine gene expression and intracellular signalling. The proportion of oxidative muscle fibre was determined by NADH staining. RESULTS: Agonist-induced PPARbeta/delta activation was only disrupted by PPARbeta/delta knockout. We also found that the disruption of the PGC-1alpha-PPARbeta/delta axis did not affect whole-body metabolism under basal conditions. As expected, PGC-1alpha mTg mice exhibited higher exercise performance, peak oxygen consumption and lower blood lactate levels following exercise, though PPARbeta/delta mKO + PGC-1alpha mTg mice showed a similar phenotype. Similarly, we found that PPARbeta/delta was dispensable for PGC-1alpha-mediated enhancement of an oxidative phenotype in skeletal muscle. CONCLUSIONS/INTERPRETATION: Collectively, these results indicate that PPARbeta/delta is not an essential partner of PGC-1alpha in the control of skeletal muscle energy metabolism. PMID- 25116182 TI - Aspirin-responsive, migraine-like transient cerebral and ocular ischemic attacks and erythromelalgia in JAK2-positive essential thrombocythemia and polycythemia vera. AB - Migraine-like cerebral transient ischemic attacks (MIAs) and ocular ischemic manifestations were the main presenting features in 10 JAK2(V617F)-positive patients studied, with essential thrombocythemia (ET) in 6 and polycythemia vera (PV) in 4. Symptoms varied and included cerebral ischemic attacks, mental concentration disturbances followed by throbbing headaches, nausea, vomiting, syncope or even seizures. MIAs were frequently preceded or followed by ocular ischemic events of blurred vision, scotomas, transient flashing of the eyes, and sudden transient partial blindness preceded or followed erythromelalgia in the toes or fingers. The time lapse between the first symptoms of aspirin-responsive MIAs and the diagnosis of ET in 5 patients ranged from 4 to 12 years. At the time of erythromelalgia and MIAs, shortened platelet survival, an increase in the levels of the platelet activation markers beta-thromboglobulin and platelet factor 4 and also in urinary thromboxane B2 were clearly indicative of the spontaneous in vivo platelet activation of constitutively JAK2(V617F)-activated thrombocythemic platelets. Aspirin relieves the peripheral, cerebral and ocular ischemic disturbances by irreversible inhibition of platelet cyclo-oxygenase (COX 1) activity and aggregation ex vivo. Vitamin K antagonist, dipyridamole, ticlopidine, sulfinpyrazone and sodium salicylate have no effect on platelet COX 1 activity and are ineffective in the treatment of thrombocythemia-specific manifestations of erythromelalgia and atypical MIAs. If not treated with aspirin, ET and PV patients are at a high risk of major arterial thrombosis including stroke, myocardial infarction and digital gangrene. PMID- 25116183 TI - Antimicrobial Constituents of the Mature Carpels of Manglietiastrum sinicum. AB - Seven new compounds, including a eupodienone-type lignan (1), a dibenzocyclooctadiene-type lignan (2), three tetrahydrofuran-type lignans (3-5), and two 1-phenylbutyl benzoates (6, 7), together with six known compounds, were isolated from the mature carpels of Manglietiastrum sinicum. The structures of new compounds 1-7 were defined by spectroscopic techniques, and the absolute configuration of manglisin A (1) was determined by X-ray crystallography. Compounds 1-4 exhibited moderate antimicrobial activities (MIC values: 0.016-0.14 MUM) against Staphylococcus aureus, MRSA 82(#), MRSA 92(#), MRSA 98(#), and MRSA 331(#). Compounds 2 and 3 showed weak cytotoxic activity against five human tumor cell lines. PMID- 25116184 TI - Factors associated with recommitment of NGRI acquittees to a forensic hospital. AB - The current archival study assesses risk factors associated with recommitment of 142 individuals adjudicated Not Guilty by Reason of Insanity (NGRI) from civil settings to a forensic hospital in New York State. Within 10 years of transfer from a forensic hospital, 40 (28.2%) were recommitted. Using survival analyses to account for the wide range in opportunity for recommitment, period of transfer (i.e., pre versus post the 1995 case of George L, which clarified factors related to assessments of dangerousness) and the Historical scale and specific items of the HCR-20 emerged as important risk factors for recommitment. Specifically, hazard of recommitment was 2.9 times higher for those with high Historical scores as compared to those with low scores. However, few individual risk factors were associated with recommitment. Prior supervision failure, negative attitude, problems with substance use, and absent or less serious major mental illness and relationship problems were informative in predicting recommitment over 10 and 3 year follow-up periods. PMID- 25116185 TI - An efficient rose bengal based nanoplatform for photodynamic therapy. AB - Organically modified mesoporous silica nanoparticles (MSNs) containing rose bengal (RB), a xanthene dye, were successfully synthesized. RB-modified MSNs have shown a relevant photostability and a high efficiency in the photoproduction and delivery of singlet oxygen ((1)O2), which is particularly promising for photodynamic therapy (PDT) applications. In vitro tests have evidenced that RB MSNs are able to reduce cell proliferation in one of the most aggressive skin cancer types (SK-MEL-28) after green-light irradiation. PMID- 25116186 TI - Laboratory surveillance of dengue in Rio Grande do Sul, Brazil, from 2007 to 2013. AB - BACKGROUND: According to official records, dengue was introduced in Brazil in the 80's; since then several epidemics have occurred. Meanwhile, in Rio Grande do Sul (RS, Southern Brazil) the first autochthonous case occurred only in 2007. METHODOLOGY AND PRINCIPAL FINDINGS: In this study we report laboratory surveillance of dengue cases and seasonality of positive cases, describe serotypes and characterize the epidemiological pattern of dengue in RS from 2007 to 2013. A total of 9,779 serum samples from patients with suspected dengue fever were collected and submitted to molecular and/or serological analyses for dengue virus identification and serotyping, based on viral isolation, NS1 antigen detection and qRT-PCR, or Dengue IgM capture ELISA and MAC-ELISA. The first autochthonous dengue case in RS was confirmed in 2007 (DENV-3). While in 2008 and 2009 only imported cases were registered, autochthonous infection waves have been occurring since 2010. The highest number of dengue infections occurred in 2010, with DENV-1 and DENV-2 outbreaks in Northwestern RS. In 2011, another DENV-1 and DENV-2 outbreak occurred in the Northwestern region; moreover, DENV-4 was detected in travelers. In 2012, DENV-1 and DENV-4 co-circulated. DENV-2 circulation was only detected again in 2013, in high frequency (56.7%), co circulating with DENV-4 (35%). Most infections occur in adults during summer. Differences in prevalence between genders were observed in 2007 (60% females), 2008 (60.8% males) and 2009 (77.5% males). CONCLUSIONS: According to results of dengue surveillance, there was an increase in the number of dengue cases in RS and of cities infested with Aedes aegypti, possibly as a consequence of introduction of new serotypes and the difficulty of health programs to control the vector. PMID- 25116187 TI - Impact of TCF3 rearrangement on CNS relapse in egyptian pediatric acute lymphoblastic leukemia. AB - BACKGROUND: TCF3 rearrangement mostly t(1;19) (q23;p13)/ TCF3-PBX1 gene is associated with favorable outcome in acute lymphoblastic leukemia (ALL) upon treatment with intensification protocols; however, it is associated with higher incidence of central nervous system (CNS) relapse which may affect outcome of patients. OBJECTIVES: We aimed to assess TCF3 rearrangement in newly diagnosed pediatric ALL patients in relation to clinical and laboratory parameters, CNS relapse, and clinical outcome. PATIENTS AND METHODS: Eighty newly diagnosed pediatric ALL patients following at Pediatric Hematology Oncology Clinic, Ain Shams University Hospitals were included in this study. Their ages ranged from 0.75 to 16 years. Seventy six (95%) patients had B-lineage ALL and four (5%) had T-lineage ALL. Data recorded included; age, sex, extramedullary manifestations, CNS, and testes infiltrations, risk stratification, response to treatment, and CBC and BM findings. TCF3 rearrangement was assessed by FISH technique using dual color break-apart probe. RESULTS: TCF3 rearrangement [t(1;19) (q23;p13)] was detected in 16 (20%) out of the 80 studied patients, and it was significantly associated with splenomegaly, lymphadenopathy, CNS infiltration at presentation, high total leucocytic count, low platelet count, high-risk group, and isolated CNS relapse. These results identify a group of high-risk ALL patients with high incidence of CNS relapse and poor response to standard therapeutic regimen. CONCLUSION: Analysis of TCF3 rearrangement [t(1;19) (q23;p13)] at diagnosis may provide a valuable target for modified and intensified CNS-directed chemotherapeutic protocol aiming to improve the patients' outcome. PMID- 25116188 TI - Recent declines in nonmarital childbearing in the United States. AB - There were sharp increases in nonmarital childbearing from 2002 to 2007, following the steady increases beginning in the 1980s. The upward trends have mainly reversed since 2007-2008. In addition, the nature of nonmarital childbearing may be changing as cohabiting unions have increased over the last few decades in the United States along with pregnancies within those unions. Births to unmarried women are at greater risk for adverse outcomes, including low birth weight, preterm birth, and infant mortality. Social and financial supports for unmarried mothers may be limited. This report describes recent trends in nonmarital births from the National Vital Statistics System (NVSS) and in cohabitation for unmarried mothers using data from the National Survey of Family Growth (NSFG). PMID- 25116189 TI - Efficient synthesis of conformationally constrained, amino-triazoloazepinone containing di- and tripeptides via a one-pot Ugi-Huisgen tandem reaction. AB - Herein we describe a catalyst-free procedure employing an Ugi-4CR between a beta azido-alpha-amino acid, propargylamine, an isocyanide and an aldehyde, followed by a thermal azide-alkyne Huisgen cycloaddition to generate a 16-member library of amino-triazoloazepinone-bearing di- and tripeptides with up to four points of diversification and high atom economy. PMID- 25116190 TI - Implementation of an acute surgical admission ward. AB - BACKGROUND: The aim of the study was to assess the impact of an acute surgical admission ward on admission and discharge processes. METHODS: This prospective cohort study was conducted in a university tertiary referral centre. All acute surgical patients were clustered in the acute surgical unit (ASU) in February and March 2012, and discharged or transferred to specialized departments within 48 h. The primary outcome was length of hospital stay (LOS). Secondary outcomes were impact on emergency department waiting times, discharge home within 48 h, incorrect ward admissions, readmissions and mortality. Outcomes of the study group were compared with those of a historical reference group admitted during the same interval the year before. RESULTS: Some 249 patients were admitted to the ASU during the study interval. The reference group consisted of 211 patients. The total LOS decreased significantly from a median of 4.0 to 2.0 days (P = 0.004). The percentage of patients who were discharged within 48 h increased from 30.3 to 43.4 per cent (P = 0.004). The rate of incorrect ward admission decreased from 9.5 to 0 per cent. Emergency department waiting time, readmission rate and 30-day mortality did not change. CONCLUSION: Introduction of an acute surgical unit-shortened length of hospital stay without comprising readmission and mortality rates. PMID- 25116191 TI - Duration of luteal support after IVF is important, so why is there no consistency in practice? The results of a dynamic survey of practice in the United Kingdom. AB - Luteal support is considered as an essential component of IVF treatment following ovarian stimulation and embryo transfer. Several studies have consistently demonstrated a benefit of luteal support compared with no treatment and whilst a number of preparations are available, no product has been demonstrated as superior. There is an emerging body of evidence which suggests that extension of luteal support beyond biochemical pregnancy does not confer a benefit in terms of successful pregnancy outcome. We performed two surveys separated by 5 years of practice evolution, with the latter reporting on the use of luteal support in all IVF clinics in the UK. All clinics reported utilising luteal support with the majority favouring the use of Cyclogest 400 mg twice daily. In contrast, there was no consensus on the optimal duration of luteal support. Whilst 24% of clinics withdrew luteal support at biochemical confirmation of pregnancy, 40% continued treatment until 12 weeks gestation. Several clinics even extended luteal support beyond 12 weeks gestation. We observed no difference in practice based on the size of the IVF unit or treatment funding source. Although there was some change in practice between surveys in many clinics, there was no uniformity in the direction of change. PMID- 25116192 TI - Global Toll-like receptor 4 knockout results in decreased renal inflammation, fibrosis and podocytopathy. AB - BACKGROUND AND PURPOSE: Type 1 diabetes mellitus (T1DM) is a pro-inflammatory state with increased toll-like receptor (TLR) activity. Inflammation is crucial in diabetic nephropathy (DN). We tested the effect of global deficiency of TLR4 on renal inflammation, fibrosis and podocytopathy using control (C) and streptozotocin (STZ) induced diabetic wildtype (WT) and TLR4-knockout (TLR4KO) mice. METHODS: Following STZ treatment, mice were euthanized at 17weeks and plasma and kidneys collected. RESULTS: Compared to C, STZ-WT mice had significantly increased macrophage and TLR4 immunostaining in kidney, significant increases in MyD88, Interferon Regulatory Factor-3, NFKappaB activity, TNF-Alpha, IL-6, and MCP-1; all these were significantly decreased in the STZ-TLR4KO compared to STZ-WT mice. Compared to C, there were significant increases in fibrosis markers (collagen 4, and transforming growth factor-beta) in STZ-WT which were significantly decreased in the STZ-TLR4KO versus STZ-WT. Podocyte numbers and podocin were decreased in the STZ-WT versus C and increased in the STZ-TLR4KO mice. CONCLUSION: Global genetic deficiency of TLR4 also ameliorates renal inflammation, fibrosis and podocytopathy and could be important in DN. PMID- 25116193 TI - The Drosophila nephrocyte has a glomerular filtration system. PMID- 25116194 TI - Reply: Nephrons are generated via a series of committed progenitors. PMID- 25116196 TI - Size tunable synthesis of solution processable diamond nanocrystals. AB - Diamond nanocrystals were synthesized catalyst-free from nanoporous carbon at high pressure and high temperature (HPHT). The synthesized nanocrystals have tunable diameters between 50 and 200 nm. The nanocrystals are dispersible in organic solvents such as acetone and are isotropic in nature as seen by dynamic light scattering. PMID- 25116195 TI - Taking a call is facilitated by the multisensory processing of smartphone vibrations, sounds, and flashes. AB - Many electronic devices that we use in our daily lives provide inputs that need to be processed and integrated by our senses. For instance, ringing, vibrating, and flashing indicate incoming calls and messages in smartphones. Whether the presentation of multiple smartphone stimuli simultaneously provides an advantage over the processing of the same stimuli presented in isolation has not yet been investigated. In this behavioral study we examined multisensory processing between visual (V), tactile (T), and auditory (A) stimuli produced by a smartphone. Unisensory V, T, and A stimuli as well as VA, AT, VT, and trisensory VAT stimuli were presented in random order. Participants responded to any stimulus appearance by touching the smartphone screen using the stimulated hand (Experiment 1), or the non-stimulated hand (Experiment 2). We examined violations of the race model to test whether shorter response times to multisensory stimuli exceed probability summations of unisensory stimuli. Significant violations of the race model, indicative of multisensory processing, were found for VA stimuli in both experiments and for VT stimuli in Experiment 1. Across participants, the strength of this effect was not associated with prior learning experience and daily use of smartphones. This indicates that this integration effect, similar to what has been previously reported for the integration of semantically meaningless stimuli, could involve bottom-up driven multisensory processes. Our study demonstrates for the first time that multisensory processing of smartphone stimuli facilitates taking a call. Thus, research on multisensory integration should be taken into consideration when designing electronic devices such as smartphones. PMID- 25116197 TI - Nanotube liquid crystal elastomers: photomechanical response and flexible energy conversion of layered polymer composites. AB - Elastomeric composites based on nanotube liquid crystals (LCs) that preserve the internal orientation of nanotubes could lead to anisotropic physical properties and flexible energy conversion. Using a simple vacuum filtration technique of fabricating nanotube LC films and utilizing a transfer process to poly (dimethyl) siloxane wherein the LC arrangement is preserved, here we demonstrate unique and reversible photomechanical response of this layered composite to excitation by near infra-red (NIR) light at ultra-low nanotube mass fractions. On excitation by NIR photons, with application of small or large pre-strains, significant expansion or contraction of the sample occurs, respectively, that is continuously reversible and three orders of magnitude larger than in pristine polymer. Schlieren textures were noted in these LC composites confirming long range macroscopic nematic order of nanotubes within the composites. Order parameters of LC films ranged from S(optical) = 0.51-0.58 from dichroic measurements. Film concentrations, elastic modulus and photomechanical stress were all seen to be related to the nematic order parameter. For the same nanotube concentration, the photomechanical stress was almost three times larger for the self-assembled LC nanotube actuator compared to actuator based on randomly oriented carbon nanotubes. Investigation into the kinetics of photomechanical actuation showed variation in stretching exponent beta with pre-strains, concentration and orientation of nanotubes. Maximum photomechanical stress of ~ 0.5 MPa W(-1) and energy conversion of ~ 0.0045% was achieved for these layered composites. The combination of properties, namely, optical anisotropy, reversible mechanical response to NIR excitation and flexible energy conversion all in one system accompanied with low cost makes nanotube LC elastomers important for soft photochromic actuation, energy conversion and photo-origami applications. PMID- 25116198 TI - Impact of high ytterbium(III) concentration in the shell on upconversion luminescence of core-shell nanocrystals. AB - After coating 20 Yb/2 Er:NaGdF4 core nanocrystals with a NaYbF4 shell, upconversion emission of the rare earth ions weakens. So far, the exact reason for this phenomenon is still unclear due to lack of the direct evidence. In this report, a core@shell@shell sandwich-like structure is designed and fabricated to investigate this phenomenon. We find that high Yb(3+) concentration in the shell has mainly two adverse impacts: it promotes not only the deleterious back energy transfer from Er(3+) in the core to Yb(3+) in the shell but also the energy transfer from Yb(3+) in the core to Yb(3+) in the shell. To obtain nanocrystals with high upconversion efficency, appropriate Yb(3+) concentration should be introduced into the shell or the transition layer. PMID- 25116199 TI - Movable magnetic porous cores enclosed within carbon microcapsules: structure controlled synthesis and promoted carbon-based applications. AB - Rattle-type porous carbon microcapsules (RPCMs) were deliberately designed to combine multiple functions with the aim of improving the applicability of amorphous carbon in a synergistic fashion. A movable Fe3O4 nanocluster coated with porous carbon is encapsulated in the cavity of a carbon microcapsule with an eggshell-like characteristic, allowing for storage, adsorption, and exchange of matters through the mesoporous channels of the carbon layer. The synthetic strategy of RPCMs is flexible and universal, involving the constitution and carbonization of Fe3O4@PF@PS@PF template particles. This results in a double carbon shell and a sandwiched hollow cavity with a movable magnetic core. There is evidence that RPCMs possess large surface areas, hierarchical pore sizes, hydrophobicity, and magnetic responsiveness. Hence, diverse applications have been investigated. It is proved that RPCMs exhibit excellent performance in the effective enrichment of peptides/proteins. The detection limit toward peptides could reach as low as 10 nM, and the enrichment capacity toward MYO protein is as high as 410 mg/g (protein/beads). Furthermore, RPCMs are able to harvest proteins in complex real samples such as fetal bovine serum and rabbit blood. In addition, RPCMs could be fabricated in a supercapacitor electrode and display outstanding energy-storage performance. The electrochemical measurements demonstrate that RPCM-based electrodes have a specific capacitance of as high as 216 F/g (0.1 A/g), long-term cycling stability with a capacitance retention of 92.4% over 1000 cycles (0.2 A/g), and good electronic conductivity. PMID- 25116200 TI - Development of a novel protocol for generating flavivirus reporter particles. AB - Infection with West Nile virus (WNV), a mosquito-borne flavivirus, is a growing public and animal health concern worldwide. Prevention, diagnosis and treatment strategies for the infection are urgently required. Recently, viral reverse genetic systems have been developed and applied to clinical WNV virology. We developed a protocol for generating reporter virus particles (RVPs) of WNV with the aim of overcoming two major problems associated with conventional protocols, the difficulty in generating RVPs due to the specific skills required for handling RNAs, and the potential for environmental contamination by antibiotic resistant genes encoded within the genome RNA of the RVPs. By using the proposed protocol, cells were established in which the RVP genome RNA is replicated constitutively and does not encode any antibiotic-resistant genes, and used as the cell supply for RVP genome RNA. Generation of the WNV RVPs requires only the simple transfection of the expression vectors for the viral structural proteins into the cells. Therefore, no RNA handling is required in this protocol. The WNV RVP yield obtained using this protocol was similar that obtained using the conventional protocol. According to these results, the newly developed protocol appears to be a good alternative for the generation of WNV RVPs, particularly for clinical applications. PMID- 25116201 TI - Establishment and application of a multiplex PCR for rapid and simultaneous detection of six viruses in swine. AB - A multiplex PCR assay was developed and evaluated subsequently for its effectiveness in simultaneously detecting mixed viral infections of swine. Specific primers were designed and used for testing the six swine viruses: three DNA viruses, including pseudorabies virus (PRV), porcine parvovirus (PPV), and porcine circovirus type 2 (PCV2); three common RNA viruses, including porcine reproductive and respiratory syndrome virus (PRRSV), classical swine fever virus (CSFV), and Japanese encephalitis virus (JEV). This technique has shown to be highly sensitive in that the minimum detection amounts of nucleic acids from PRV, PPV, PCV2, PRRSV, CSFV, and JEV were 6.6, 96, 12.9, 10.5, 51, and 46 pg, respectively. It also was effective for detecting one or multiple viruses in the specimens, such as the lungs, spleens, lymph nodes, and tonsils collected from clinically ill pigs. The multiplex PCR method can detect simultaneously not only infection of the six viruses, but also other swine DNA and RNA viruses. Given its rapidity, specificity, and sensitivity, the multiplex PCR is a useful tool for diagnosing clinically the mixed infections of swine DNA and RNA viruses. PMID- 25116202 TI - A degenerate pair of primers for simultaneous detection of four alpha- and betanecroviruses. AB - The high infection levels due to Olive latent virus 1 (OLV-1), Olive mild mosaic virus (OMMV) (alphanecrovirus) and Tobacco necrosis virus D (TNV-D) (betanecrovirus) in Portuguese olive orchards prompted us to develop a rapid PCR based assay for the simultaneous detection of these viruses aimed at the sanitary selection and marketing of plant material in compliance with European Union regulations. A pair of degenerate oligonucleotide primers, parRdRp5' and parCoat3' was designed based on conserved regions located in the RNA-dependent RNA polymerase (RdRp) and coat protein (CP) genes of these viruses and one other alphanecrovirus, Tobacco necrosis virus A. Its use in RT-PCR assays generated a product of ca. 2000 bp for the 4 viral species tested. These primers were compared with virus specific primers in multiplex RT-PCR, and identical results were obtained. Its application to dsRNA extracted from 54 olive field growing trees originated the expected ca. 2000 bp amplicon in 17 trees. The virus identity was determined by sequencing the cloned RT-PCR products. No TNV-A was found. The RT-PCR assay using the degenerate primers described in this study were shown to be reliable in detecting any of the above-mentioned alpha- and betanecroviruses, and it is as sensitive as that which uses virus specific primers in multiplex assays. Therefore, this assay is well suited for the rapid screen of virus-free plant material in selection and improvement crop programmes. Additionally, it has the potential to reveal virus diversity and the presence of new viruses, provided the RT-PCR generated amplicon is further sequenced. PMID- 25116204 TI - Cloacal defect repair--a video vignette. PMID- 25116203 TI - Prevalence and risk factors for suicidal behavior in young people presenting with first-episode psychosis in Hong Kong: a 3-year follow-up study. AB - PURPOSE: Individuals with first-episode psychosis (FEP) have markedly elevated risk for suicide. Previous research investigating risk factors of suicidal behavior in FEP mainly focused on western populations. This study aimed to examine the prevalence, and pretreatment and early illness predictors of suicidal behavior in Chinese FEP patients. METHOD: Seven hundred participants aged 15-25 years consecutively enrolled in a territory-wide treatment program for FEP in Hong Kong from July 2001 to August 2003 were studied. Baseline and 3-year follow up variables were collected via systematic medical file review. Suicidal behavior evaluated in this study comprised suicide attempt and completed suicide. RESULTS: Seventy-four (10.6%) participants attempted suicide before treatment. Ten percent (n = 70) exhibited suicidal behavior and 1% (n = 7) committed suicide during 3 year follow-up. The majority of post-treatment suicidal behaviors (51.4%) occurred in the first year of follow-up. Jumping from a height was the most common method of committing suicide. Multivariate regression analysis indicated that previous suicide attempt, history of substance abuse and poorer baseline functioning were significantly associated with an increased risk for suicidal behavior after treatment initiation. CONCLUSION: In a large representative cohort of Chinese young FEP patients, the rates of suicidal behavior before and after treatment and risk factors for post-treatment suicidal behavior were comparable to the findings of previous research on early psychosis conducted in western populations. Close monitoring of high-risk patients with history of attempted suicide or substance abuse, and enhancement of psychosocial functioning may help reduce suicide risk in the early stage of psychotic illness. PMID- 25116205 TI - Attaining khinem: challenges, coping strategies and resilience among Eveny adolescents in northeastern Siberia. AB - This article examines challenges, coping strategies, and resilience among Eveny adolescents in northeastern Siberia. It explores situations which the study participants associate with challenge and hardship, namely their experiences of transition from life in the family reindeer herding camp to schooling at the age of 7, bullying, boredom, and violence. By situating the data within the Eveny framework of resilience (khinem), the study provides the ethnographic context for coping strategies and efforts (e.g., sharing, inter- and intragenerational support, availability of safe homes) undertaken by the community in order to mitigate the situations of risk and hardship and to facilitate adolescents' resilience. The account emphasizes that instead of identifying adolescents as either resilient or vulnerable, it is necessary to explore culturally specific processes and practices which potentially contribute to their acquisition of resilience. PMID- 25116207 TI - Concussion 101 for SLPs. PMID- 25116208 TI - Medical treatment of concussion. AB - A concussion is a brain injury, a change in function induced by traumatic forces. The incidence of concussion is increasing, likely due to increased awareness and improvement in recognition. Speech and language pathology professionals working in schools may encounter patients who have suffered concussions. At the root of concussion pathophysiology is altered metabolism and an acquired energy deficit. The mainstay of treatment for concussion is cognitive and physical rest, allowing for normalization of the metabolism and correction of the energy deficit. Once recovered, the student may need accommodations to successfully return to school without added difficulty and should follow a return to play protocol to return to athletics safely. PMID- 25116209 TI - Neurometabolic aspects of sports-related concussion. AB - Concussion is a transitory brain injury resulting from a blow to the head. Concussion is considered a mild traumatic brain injury (mTBI), which is self limited. Repetitive mTBI has been associated with chronic, progressive neurologic damage. Extreme biochemical changes occur in neuron cells as a result of mTBI. These metabolic disturbances may reflect the symptoms observed in patients who had concussions. However, it has been difficult to match clinical signs and symptoms. Currently, there is no test to diagnose concussion. Further studies are needed to elucidate the biochemical details of the metabolic cascade and the associated time frame, which will help determine when an athlete can safely return to the game. PMID- 25116206 TI - Collagen can selectively trigger a platelet secretory phenotype via glycoprotein VI. AB - Platelets are not only central actors of hemostasis and thrombosis but also of other processes including inflammation, angiogenesis, and tissue regeneration. Accumulating evidence indicates that these "non classical" functions of platelets do not necessarily rely on their well-known ability to form thrombi upon activation. This suggests the existence of non-thrombotic alternative states of platelets activation. We investigated this possibility through dose-response analysis of thrombin- and collagen-induced changes in platelet phenotype, with regards to morphological and functional markers of platelet activation including shape change, aggregation, P-selectin and phosphatidylserine surface expression, integrin activation, and release of soluble factors. We show that collagen at low dose (0.25 ug/mL) selectively triggers a platelet secretory phenotype characterized by the release of dense- and alpha granule-derived soluble factors without causing any of the other major platelet changes that usually accompany thrombus formation. Using a blocking antibody to glycoprotein VI (GPVI), we further show that this response is mediated by GPVI. Taken together, our results show that platelet activation goes beyond the mechanisms leading to platelet aggregation and also includes alternative platelet phenotypes that might contribute to their thrombus-independent functions. PMID- 25116210 TI - Community-based resources for concussion management. AB - Speech-language pathologists can serve an important role as members of interdisciplinary treatment teams in the rehabilitation of concussion-related cognitive-communicative changes in the community setting. This article discusses the continuum of care for individuals who have experienced concussion and the importance of appropriate assessment and functionally based intervention. Factors such as executive function impairments, sensory overload, and cognitive exertion can yield subtle deficits that can impact functional return to work or school. Community resources such as support groups are discussed, as well as the impact of state and federal policies related to concussion on community activities. PMID- 25116211 TI - Clinical test instrument development to identify and track recovery from concussion. AB - Over the past 25 years, neuropsychological assessment has been the prominent clinical method for evaluating neurocognitive functioning and monitoring recovery following mild traumatic brain injury (mTBI), or concussion. During this time, neuropsychological assessment of concussion has developed extensively starting from traditional paper-and-pencil tests to the more current computerized assessment batteries that are specifically designed for evaluating mTBI. Concussion assessment is complex and challenging due to the highly variable neurocognitive behavior and the wide range of diverse symptoms that follow an injury. Therefore, neuropsychological testing is only one component of a multifaceted, comprehensive assessment approach that also includes balance testing and symptom assessment. Because concussions may go undetected, more emphasis has been placed on objective and sensitive neuropsychological measures. Factors that could affect the validity of test performance include athletes not recognizing or intentionally hiding their symptoms or sandbagging their baseline performance. Due to the complex nature of identifying and evaluating mild head injuries, the purpose of this review is to discuss (1) the clinical use of neuropsychological testing in concussion management, (2) the methods used for evaluating and monitoring recovery following concussion, (3) the characteristics of current assessment instruments, and (4) additional clinical factors and approaches for concussion assessment and management. PMID- 25116212 TI - Clinical assessment of balance in adults with concussion. AB - Balance is a key component to the assessment of concussion injury; however, the efficacies of clinical tests used are currently under debate. It is questionable whether currently accepted methods of standing balance assessment quantify balance disturbances sufficiently to support decisions on recovery and return to play. Recent evidence of balance abnormalities postconcussion that linger beyond the typical 3- to 5-day recovery period support arguments that currently available standing balance tests are not sensitive enough to determine recovery of function. This article discusses the current clinical tests used in the assessment of concussion in adults and their limitations and the evidence supporting continued balance dysfunction. Implications for the future of balance assessment in concussed adults and recommendations to clinicians for best practices are presented. PMID- 25116213 TI - Pharmacological management of traumatic brain injury and implications for speech language pathology. AB - This article provides an overview of the pharmacological management of traumatic brain injury (TBI). A basic introduction to key pharmacokinetic and pharmacodynamic principles is used to guide the reader. The goals of the pharmacological management of TBI are explained starting with mild TBI. The main medications used for each medical condition are described with a primary emphasis of effects that may interfere with the role of speech-language pathology (SLP). Some medications may interfere with cognitive, motor, and neuromuscular functions, and others may cause ototoxicity. A basic overview of the pharmacological management of moderate to severe TBI is included because the SLP practitioner may encounter patients with TBI during the recovery phase. The importance of assessment of swallowing evaluations is discussed because the oral route of administration of medications is preferred once the patient is stable. PMID- 25116214 TI - Management of athletes with postconcussion syndrome. AB - Rehabilitation for athletes with postconcussion syndrome requires emphasis on both cognitive and physical rest with a gradual return to activity and sports. As the athlete becomes more active, the rehabilitation and sport professional should pay close attention to symptoms of concussion, like headache, dizziness, nausea, and difficulty concentrating. The Zurich Consensus Statement on Concussion in Sport provides a systematic approach to increasing the intensity of physical activity while attending to postconcussion symptoms. During the incident that led to a concussion, the injured athlete may have incurred injuries to the vestibular and balance system, which are not directly related to concussion. These conditions are best addressed by professionals with specific training in vestibular rehabilitation, most commonly physical therapists. Benign paroxysmal positional vertigo is a condition in which otoconia particles in the inner ear dislodge into the semicircular canals, resulting in severe vertigo and imbalance. This condition frequently resolves with a few sessions with a vestibular therapist and a home exercise program. In conditions like gaze instability, motion sensitivity, impaired postural control, and cervicogenic dizziness, improvement is more gradual and requires longer follow-up with a physical therapist. In all of these conditions, it is important to consider that the patient with postconcussion syndrome will likely recover more slowly than others and should be monitored for symptoms of postconcussion syndrome throughout intervention. PMID- 25116215 TI - A model of prevention of sports concussion in adults. AB - This article discusses the definitions of prevention and presents a model that addresses multidimensional aspects of sports concussion prevention from the perspectives of epidemiology, education, environmental modification, enforcement, and evaluation. Epidemiology is helpful in identifying the incidence of concussion and the interventions most likely to reduce its occurrence. Education ensures that accurate information on concussion is communicated to stakeholders. Modifications in the physical and sociocultural environments may lessen the potential for injury and reduce the risk of concussion. Enforcement of legislation standards can be effective in concussion prevention, especially at the preinjury and injury phases. The evaluation dimension assesses the effectiveness of prevention programs and guides future program development. This five-E model explains concussion prevention as a recursive loop process. Each dimension is closely associated in the prevention of sports concussion. PMID- 25116216 TI - Clinical assessment of motor speech disorders in adults with concussion. AB - This article reviews the occurrence of motor speech disorders of dysarthria and apraxia of speech following closed head injury and other traumatic brain injuries in adults as they apply to sport concussion and related trauma. Athletic sideline and speech-language pathology screenings are considered. Procedures for clinical assessment and diagnosis of motor speech disorder, most particularly dysarthria, are discussed with special reference to closed head injury. Included are the evaluation components of cranial nerve and speech mechanism examination, nonspeech musculature examination, perceptual and instrumental assessment procedures, quasi-standardized testing for dysarthria, and the determination of restrictions of participation in everyday life activities. The resultant output of such an evaluation is described in depth. Future directions for clinical research on motor speech disorders following sports concussion are also briefly considered. PMID- 25116217 TI - Future of traumatic brain injury in adults. AB - The previous articles in this compendium reviewed the past, present, and future status of the diagnosis, prognosis, treatment, and prevention of mild traumatic brain injury in the adult population. This article will discuss the issue of when an individual should initiate the return-to-play (or class or work) protocol. The clinical criterion to initiate the return-to-play protocol consists of neuropsychological performance that returns to baseline and is stable, with no reported symptoms. Recent functional magnetic resonance imaging (fMRI) studies raise serious questions about these clinical criteria. fMRI results in individuals with concussion are different from those of normal controls. Does this difference represent cortical reorganization and/or cortical dysfunction? If the imaging results reflect neuroplastic reorganization, then the initiation of the return-to-play protocol is acceptable. However, if the imaging differences indicate cortical dysfunction, then initiation of the return-to-play protocol would not be advised. This article will describe the problem, the data available to address this problem, and future research needs. PMID- 25116219 TI - Bioimpedance in 7-year-old children: validation by dual X-ray absorptiometry - part 2: assessment of segmental composition. AB - AIM: Segmental body composition in children was assessed using the bioimpedance analyzer (BIA) TANITA BC-418 and compared with dual-energy X-ray absorptiometry (DXA) values. METHODS: A cross-sectional validation study in which 7-year-old children from the Spanish subsample of the EU Childhood Obesity Project were assessed through anthropometry, BIA and DXA. Main outcome measures were fat and lean masses of the trunk, left arm and left leg (in kg) assessed through BIA direct outputs (BIAoutputs) and DXA. Predictive equations for the composition of each segment were derived from raw impedance and anthropometric measurements; results obtained from these predictive equations (BIAregressions) were also compared to DXA. RESULTS: One hundred seventy-one (84 boys) 7-year-old children were studied. BIAoutputs and DXA results showed small differences for leg lean mass (6.5%) and high differences for trunk fat and trunk lean masses (>30%). BIAregressions results showed differences of about 20% for trunk fat mass, 1.5% for trunk lean mass and 3.7% for leg lean mass compared to DXA. CONCLUSIONS: Segmental body composition measures predicted by internal algorithms of the TANITA BC-418 were not valid for clinical or epidemiological use, except for leg lean mass. The assessment of segmental composition was improved using our own predictive equations combining segmental-specific anthropometric measurements with segmental impedances. PMID- 25116218 TI - Comparison of the long-term effects on rabbit bone defects between Tetrabone and beta-tricalcium phosphate granules implantation. AB - Tetrabone is a newly developed granular artificial bone. The 1-mm Tetrabone has a four-legged structure. In this study, the long-term effect of implanting Tetrabone or beta-TCP granules in rabbit femoral cylindrical defects was evaluated. The rabbits were euthanized at 4, 13, and 26 weeks after implantation. Micro-CT was conducted to evaluate the residual material volume and the non osseous tissue volume. New bone tissue areas were measured by histological analysis. Micro-CT imaging showed that the residual material volume in the beta TCP group had decreased significantly at 4 weeks after implantation (P < 0.05) and that the beta-TCP granules had nearly disappeared at 26 weeks after implantation. In the Tetrabone group, it did not significantly change until 13 weeks after implantation; it then continued to decrease slightly until 26 weeks after implantation. The non-osseous volume increased in the beta-TCP group, whereas that of the Tetrabone group decreased (P < 0.05). Histological examination showed that the new bone areas were significantly greater in the Tetrabone group than in the beta-TCP group at 13 and 26 weeks. In conclusion, resorption of beta-TCP granules occurs before sufficient bone formation, thereby allowing non-osseous tissue invasion. Tetrabone resorption progressed slowly while the new bone tissues were formed, thus allowing better healing. Tetrabone showed better osteoconductivity, whereas the beta-TCP granules lost their function over a long duration. These results may be caused by the differences in the absorption rate of the granules, intergranular pore structure, and crystallinity of each granule. PMID- 25116220 TI - Discovering mechanistic insights by application of tandem ultrafast multidimensional NMR techniques. AB - Ultrafast multidimensional NMR acquisition techniques have shown promising capabilities in studies of dynamic systems in real time. The method's characteristics have permitted the focus to be on the mechanistic details of organic reactions. The tandem UF-TOCSY/HMBC sequence applied here combines both homonuclear and heteronuclear details and therefore provides complete information about the evolution of a dynamic reaction in real time. The methodology will be applied to find an explanation of the low reactivity of alicyclic ketones such as cyclohexanone in reactions with triflic anhydride and aliphatic nitriles, which leads to bicyclic pyrimidines. PMID- 25116222 TI - GP is allowed to practise again after affair with patient. PMID- 25116221 TI - Mercury isotope study of sources and exposure pathways of methylmercury in estuarine food webs in the Northeastern U.S. AB - We measured mercury (Hg) isotope ratios in sediments and various estuarine organisms (green crab, blue mussel, killifish, eider) to investigate methylmercury (MMHg) sources and exposure pathways in five Northeast coast (U.S.) estuaries. The mass independent Hg isotopic compositions (MIF; Delta(199)Hg) of the sediments were linearly correlated with the sediment 1/Hg concentrations (Delta(199)Hg: r(2) = 0.77, p < 0.05), but the mass dependent isotope compositions (MDF; delta(202)Hg) were not (r(2) = 0.26, p = 0.16), reflecting inputs of anthropogenic Hg sources with varying delta(202)Hg. The estuarine organisms all display positive Delta(199)Hg values (0.21 to 0.98 0/00) indicating that MMHg is photodegraded to varying degrees (5-12%) prior to entry into the food web. The delta(202)Hg and Delta(199)Hg values of most organisms can be explained by a mixture of MMHg and inorganic Hg from sediments. At one contaminated site mussels have anomalously high delta(202)Hg, indicating exposure to a second pool of MMHg, compared to sediment, crabs and fish. Eiders have similar Delta(199)Hg as killifish but much higher delta(202)Hg, suggesting that there is an internal fractionation of delta(202)Hg in birds. Our study shows that Hg isotopes can be used to identify multiple anthropogenic inorganic Hg and MMHg sources and determine the degree of photodegradation of MMHg in estuarine food webs. PMID- 25116223 TI - Using an unconventional perfusion pattern in ear replantation-arterialization of the venous system. AB - Ear amputation is a devastating injury characterized by a conspicuous deformity that is not easily concealed and can result in tremendous psychological trauma in addition to the physical insult. While numerous different approaches have been proposed, microvascular replantation is widely considered to deliver the best esthetic outcome. In this article, the authors report a case in which an unconventional perfusion pattern (i.e., arterialization of the venous system) was chosen, as intraoperative anatomic conditions precluded conventional vascular reconstruction. A 25-year-old male patient sustained a human bite resulting in subtotal amputation of his left ear. In the setting of an adequate arterial donor vessel, that is, branch of the posterior auricular artery, and a single suitable recipient vein (0.4 mm), the decision was made to perform an end-to-end arterio venous anastomosis without the use of vein grafts. Medicinal leeches were applied postoperatively to provide for venous drainage. The ear survived and the patient was discharged after 14 days. To the best of our knowledge, this is first case of a subtotal ear amputation that was successfully replanted by arterialization of the venous system without the use of vein grafts and with preservation of the superficial temporal vessels. PMID- 25116224 TI - Potential protection of vitamin C against liver-lesioned mice. AB - Pathologically, liver injury can result from sustained trauma to hepatocytes, including acute damage. Thus, attenuation of hepatocellular lesion may help improve liver functions. The purpose of this study was to explore the potential advantages of vitamin C (VC) intake on acutely intralesional liver in carbon tetrachloride (CCl4)-exposed mice. Here our data showed that VC supplementation contributed to ameliorated vital signs of CCl4-lesioned mice, resulting in dose dependent reduction of hepatomegaly. VC lowered the levels of liver functional enzymes including alanine aminotransferase (ALT) and glutamic-oxaloacetic transaminase (AST) in serum, while concentration of lactic acid concentration in blood plasma was decreased. VC-administered CCl4-lesioned mice manifested increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), while the malondialdehyde (MDA) content was reduced in liver tissue. Moreover, VC consumption attenuated hepatotoxic injuries of CCl4-lesioned mice, in which the number of TNF-alpha positive cells was dose-dependently reduced. Furthermore, intrahepatic expression of TRL-4 mRNA, a vital inflammation regulator, was down-regulated in VC-administered mice. Overall, we conclude that VC has the potentiality of anti-hepatotoxicity that is capable of ameliorating liver functions, speculating that therapeutic mechanism relates to normalizing metabolism and blocking inflammatory stress in the liver. PMID- 25116225 TI - Effect of Kuwanon G isolated from the root bark of Morus alba on ovalbumin induced allergic response in a mouse model of asthma. AB - The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used in Korean medicine for upper respiratory diseases. In this study, we investigated the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA) induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered orally in mice once a day for 7 days during OVA airway challenge. We measured the levels of OVA-specific IgE and Th2 cytokines (IL-4, IL-5, and IL-13) in the sera or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G significantly decreased the levels of OVA-specific IgE and IL-4, IL-5, and IL-13 in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of inflammatory cells in the BAL fluids of asthma mice. Furthermore, the pathological feature of lungs including infiltration of inflammatory cells, thickened epithelium of bronchioles, mucus, and collagen accumulation was inhibited by kuwanon G. These results indicate that kuwanon G prevents the pathological progression of allergic asthma through the inhibition of lung destruction by inflammation and immune stimulation. PMID- 25116226 TI - Multivertebral tubercular spondylodiscitis with abscesses in acute lymphoblastic leukemia. PMID- 25116227 TI - Summary health statistics for u.s. Adults: national health interview survey, 2003. AB - Objectives-This report presents health statistics from the 2003 National Health Interview Survey for the civilian noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, education, income, poverty status, health insurance coverage, marital status, place of residence, and region of residence for chronic condition prevalence, health status, functional limitations, health care access and utilization, health behaviors, and human immunodeficiency virus testing. Percentages and percent distributions are presented in both age-adjusted and unadjusted versions. Source of Data-The NHIS is a household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics. In 2003, data were collected for 30,852 adults for the Sample Adult questionnaire. The conditional response rate was 84.5%, and the final response rate was 74.2%. The health information for adults in this report was obtained from one randomly selected adult per family. Highlights-In 2003, 62% of adults 18 years of age or over reported excellent or very good health. Fifty-nine percent of adults never participated in any type of vigorous leisure-time physical activity, and 14% of adults did not have a usual place of health care. Eleven percent of adults had been told by a doctor or health professional that they had heart disease, and 21% had been told on two or more visits that they had hypertension. Twenty-two percent of all adults were current smokers, and 22% were former smokers. Based on estimates of body mass index, 36% of adults were overweight and 23% were obese. PMID- 25116228 TI - Secondary malignant neoplasms among children, adolescents, and young adults with osteosarcoma. AB - BACKGROUND: As patients with osteosarcoma become long-term survivors, increasing attention has turned to the burden of late effects. The goal of the current study was to describe the incidence, characteristics, and outcomes of secondary malignant neoplasms (SMNs) in this population. METHODS: Patients aged birth to 40 years at time of primary diagnosis with osteosarcoma and reported to the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2010 were eligible for inclusion in the cohort. Competing risks methods were used to estimate the cumulative incidence of SMNs and potential risk factors for developing an SMN. Standardized incidence ratios (SIR) and overall survival after an SMN were estimated. RESULTS: The SEER database included 3379 patients who were diagnosed with osteosarcoma as their first malignancy. Of these, 89 patients were diagnosed with an SMN. The cumulative incidence of any SMN was 2.1% (95% confidence interval [95% CI], 1.6%-2.7%) at 10 years, 4.0% (95% CI, 3.1%-5.1%) at 20 years, and 7.4% (95% CI, 5.6%-9.5%) at 30 years. The median time from the primary diagnosis to an SMN diagnosis was 6.0 years. The SIR for SMNs for survivors of osteosarcoma compared with the general population was 1.6 (95% CI, 1.0-2.5) for patients diagnosed with osteosarcoma from 1973 through 1985 and 4.7 (95% CI, 3.3-6.4) for patients diagnosed with osteosarcoma from 1986 through 2010, with a 34-fold increased risk of leukemia in this most recent era. The overall survival rate at 5 years for patients with SMNs after a diagnosis of osteosarcoma was 44.5%. CONCLUSIONS: Survivors of osteosarcoma are at an increased risk of developing SMNs compared with the baseline population, with an increased risk noted in patients treated in the more recent era. PMID- 25116229 TI - Serum hepcidin measured by immunochemical and mass-spectrometric methods and their correlation with iron status indicators in healthy children aged 0.5-3 y. AB - BACKGROUND: The diagnostic use of hepcidin is limited by the absence of standardization and lack of age-specific reference ranges in children in particular. The aim of this study was to determine reference ranges of serum hepcidin in healthy children aged 0.5-3 y using mass spectometry (MS) and a commercial immunochemical (IC) assay, and to investigate its association with other indicators of iron status and inflammation. METHODS: We included 400 healthy children aged 0.5-3 y. We constructed reference ranges for MS-hepcidin and IC-hepcidin concentrations using the median, P2.5, and P97.5 in a normative population of 219 children with no anemia, no infection and/or inflammation, and no iron deficiency. RESULTS: Median concentrations (P2.5-P97.5) of MS-hepcidin and IC-hepcidin were 3.6 nmol/l (0.6-13.9 nmol/l) and 7.9 nmol/l (1.9-28.6 nmol/l), respectively. We found a good correlation between both methods. However, MS-hepcidin was consistently lower than IC-hepcidin. Hepcidin correlated with ferritin and C-reactive protein. CONCLUSION: We provide reference ranges for hepcidin for an MS and commercial IC method. Absolute values between assays differed significantly, but hepcidin concentrations obtained by MS and IC methods correlate with each other, and both correlate with ferritin and CRP. PMID- 25116230 TI - Cardiovascular risk markers until 12 mo of age in infants fed a formula supplemented with bovine milk fat globule membranes. AB - BACKGROUND: Some of the health advantages of breast-fed as compared to formula fed infants have been suggested to be due to metabolic programming effects resulting from early nutrition. METHODS: In a prospective double-blinded randomized trial, 160 infants <2 mo of age were randomized to experimental formula (EF) with added milk fat globule membrane (MFGM) or standard formula (SF) until 6 mo of age. A breast-fed reference (BFR) group consisted of 80 infants. Measurements were made at inclusion and at 4, 6, and 12 mo of age. RESULTS: During the intervention, the EF group had higher total serum cholesterol concentration than the SF group, reaching the level of the BFR group. The EF group had a low-density lipoprotein to high-density lipoprotein ratio not significantly different from the SF group but lower than the BFR group. CONCLUSION: Supplementation of infant formula with MFGM modified the fat composition of the formula and narrowed the gap between breast-fed and formula fed infants with regard to serum lipid status at 12 mo. PMID- 25116231 TI - Fibrous Tendon Hypertrophy after Gastrocnemius Recession: A Case Report. AB - Surgical complications after gastrocnemius recession have been rare in published studies. We report a case of symptomatic fibrous tendon hypertrophy requiring revision surgery. Additionally, we have provided a review of the published data on the complications related to this procedure. PMID- 25116232 TI - A biomechanical comparison of internal fixation techniques for ankle arthrodesis. AB - The purpose of the present study was to compare the primary bending stiffness characteristics of 5 different ankle arthrodesis fixation techniques: 3 compression screws, an anterior locking plate, a lateral locking plate, an anterior locking plate with a compression screw, and a lateral locking plate with a compression screw. A total of 25 full-scale anatomic models consisting of fourth-generation composite tibiae and tali were tested using an Instron 4505 Universal Testing System. We hypothesized that the use of a compression screw with a locking plate would add considerable stiffness to the fixation construct compared with the use of a locking plate alone. The data have shown that an anterior or lateral plate with a compression screw provides significantly greater stiffness than both a plate and 3 compression screws used individually. No significant difference was seen between the anterior plate with a compression screw and the lateral plate with a compression screw. No significant differences were found among the use of an anterior plate, a lateral plate, or 3 compression screws. We have concluded that when using a locking plate in an anterior or lateral configuration, the addition of a compression screw will considerably increase the primary bending stiffness of ankle arthrodesis. PMID- 25116233 TI - Tibiocalcaneal Fusion for Charcot Ankle With Severe Talar Body Loss: Case Report and a Review of the Surgical Literature. AB - Severe bone loss resulting from talar body necrosis in the Charcot ankle can be challenging to treat. In particular, the Charcot ankle will demonstrate progressive instability and deformity, causing protrusion of the medial or lateral malleolus, which will mostly lead to skin ulcers or osteomyelitis and, in some cases, will ultimately require transtibial amputation. Problems such as bone fragility, poor compliance with load-bearing restrictions, susceptibility to infection, and circulatory disorders cause difficulties in the surgical treatment of the Charcot ankle. We believe that tibiocalcaneal fusion is a reliable method to obtain satisfactory outcomes in these difficult cases. However, no study has reported on the use of a locking plate for tibiocalcaneal fusion. Therefore, we report on tibiocalcaneal fusion using a locking plate in 3 patients with Charcot ankle and severe talar body loss. All patients achieved bony union with a plantigrade foot and without any skin complications. We have concluded that a locking plate provides rigid fixation and easier insertion of additional screws, when necessary. PMID- 25116234 TI - Women in limbo: life course consequences of infertility in a Nigerian community. AB - Infertility is a devastating problem around the world, particularly in the high fertility context of sub-Saharan Africa. Regardless of its medical origins, infertility causes African women personal grief and economic deprivation.This research was conducted among the Ijo who are organized into exogamous patrilineal descent groups. Women who marry into a patrilineage are perceived as bearers of sons who will eventually take their place in the lineage's genealogy. Women only figure in the lineage structure as mothers.In addition to extensive ethnographic research in this community, the paper is based on a combination of surveys of 246 women and interviews of 25 fertile and 25 infertile women.Women who have never given birth were characterized as "useless". Some managed to accumulate wealth or attained education but most feared a marginal old age. Respect was given to women who have had even one child, even if that child died. The biological process of gestation confers an adult status on women allowing them to undergo initiation and to function as mature individuals. In the life course the most prominent periods of suffering are the transition from the stages of ereso (girl) to erera (mature woman), and in the period of old age. PMID- 25116235 TI - Exceptionally strong and robust millimeter-scale graphene-alumina composite membranes. AB - Graphene has attracted attention as a potential strengthening material and functional component in suspended membranes as utilized in micro and nanosystems. Development of a practical and scalable fabrication process is a necessary step to allow the exceptional material properties of graphene to be fully exploited in composite structures. Using standard and scalable microfabrication processes, we fabricated free-standing chemical vapor deposition monolayer graphene-reinforced Al2O3 composite membranes, 0.5 mm in diameter, that are strong and robust. Bulge tests revealed that the graphene reinforcement increased the membrane fracture strength by a factor of at least three and maximum sustainable strain from 0.28% to at least 0.69%. We show that the graphene-reinforced membranes are even tolerant to significant cracking without loss of membrane integrity. The graphene composite membranes' freestanding area of ~ 200 000 MUm(2) is almost a thousand times larger than suspended graphene membranes reported elsewhere. The presented graphene composite membranes may be seen as representing an interesting new class of durable composite materials warranting further study and having potential for broad applicability in a variety of fields. PMID- 25116236 TI - Unraveling the enhanced photocatalytic activity and phototoxicity of ZnO/metal hybrid nanostructures from generation of reactive oxygen species and charge carriers. AB - An effective way for promoting photocatalytic activity of a semiconductor is deposition of noble metal nanoparticles (NPs) onto it. In this paper, we deposited Ag and Pd onto ZnO NPs to form ZnO/Ag and ZnO/Pd hybrid nanostructures. It was found that both Ag and Pd nanocomponents can greatly enhance the photocatalytic activity and phototoxicity of ZnO toward human skin cells. Using electron spin resonance spectroscopy with spin trapping and spin labeling techniques, we observed that either deposition of Ag or Pd resulted in a significant increase in photogenerated electrons and holes and production of reactive oxygen species including hydroxyl radicals, superoxide, and singlet oxygen. We compared the enhancing effects of Ag and Pd and found that Pd is more effective than Ag in promoting the generation of hydroxyl radicals and holes and the photocatalytic activity of ZnO. Conversely, Ag is more effective than Pd in enhancing electron transfer and the generation of superoxide and singlet oxygen. The mechanism underlying the differences in the effects of Ag and Pd may be related to differences in Fermi levels for Ag and Pd and band bending accompanied by effects on Schottky barriers. The results of these studies provide information valuable for designing hybrid nanomaterials having photocatalytic and photobiological activities useful for applications such as water purification and formulation of antibacterial products. PMID- 25116237 TI - Identification of bromophenol thiohydantoin as an inhibitor of DisA, a c-di-AMP synthase, from a 1000 compound library, using the coralyne assay. AB - c-di-AMP is an important bacterial second messenger found in Gram-positive and mycobacteria. c-di-AMP regulates myriads of processes in bacteria as well as immune response in higher organisms so interest in small molecules that would attenuate the activity of c-di-AMP metabolism enzymes is high. Herein, we report the first small molecule inhibitor of a c-di-AMP synthase, DisA, using a coralyne based assay. PMID- 25116238 TI - Statistically quantified measurement of an Alzheimer's marker by surface-enhanced Raman scattering. AB - Fibrillar forms of the Amyloid-beta (Abeta) protein have been implicated in the early stages of Alzheimer's disease (AD), however there are no standardised assays for soluble Abeta oligomer biomarkers that provide the best indication of the disease progression [1,2]. As a step towards a fast and label-free method for testing different AD biomarkers, we have combined laser nano-textured substrates with a SERS mapping technique and validated it using soluble Abeta-40 oligomers [3-5]. The nano-textured SERS substrates provide fast (&5 min), label-free spectra associated with soluble Abeta-40 oligomers down to a concentration of 10 nM. Statistical analysis of the spectral intensities mapped over the substrate surface shows a quantitative correlation with the oligomer concentration. Schematics of experiments: SERS mapping of Abeta-40 (left figure: measured SERS intensity overlayed with an SEM image of ripples) was carried out on the laser nano-textured (ripple) surface of sapphire and statistical analysis of the SERS intensity was carried out for qualitative (a high SERS intensity at low probability) and quantitative (a moderate SERS intenisty at the highest probability) measures. Quantitative statistical analysis of SERS mapping data can be performed off line for cross correlations with other known SERS signatures. PMID- 25116240 TI - [Special topics in pediatric orthopedics: options and limits of growth guidance]. AB - BACKGROUND: A main task of pediatric orthopedics is the treatment of legs of different lengths or misshapen legs. Whereas for adult patients complicated and invasive operative interventions are necessary, the growth potential of the epiphysial plate can be utilized in childhood and adolescence to correct leg length differences and leg axis deformities. THERAPY: Epiphysiodesis leads to a guidance of growth via a temporary or permanent and partial or complete blockade of the epiphysial plate depending on the indications. This method is principally a less invasive procedure with few complications. CONCLUSION: Careful preoperative assessment of the indications and planning, precise operative technique and attentive postoperative control investigations are absolutely essential for successful treatment. PMID- 25116241 TI - [Congenital dysplasia and dislocation of the hip: proven and new procedures in diagnostics and therapy]. AB - BACKGROUND: As developmental dysplasia of the hip (DDH) is the most common congenital muskuloskeletal anomaly, it seems necessary to give an update on the normal growth, pathoanatomy, diagnostic and therapeutic procedures. OBJECTIVES: Which investigations or procedures have withstood the test of time? What are new therapeutic strategies and considerations? What are the problems? METHODS: Review of the current literature on DDH supplemented by several years experience in the treatment of this condition by the authors. RESULTS: We have still a long way to achieve the goal of agreement on universal standardization of assessment and treatment methods based on age and staging regarding DDH, as in the Ponseti treatment procedure for clubfoot. CONCLUSION: Our experiences, as well as the literature suggest the use of Graf's nomenclature for classification of DDH in the first year of life. If dynamic ultrasound (US) shows at least a partial relocation of a decentered hip in the first 6 weeks of life, splinting in human position is advocated. The treatment of a Graf type IV hip joint is very difficult and often need surgery. The established surgical procedures in the literature are still up to date. Radiological follow-up of the affected as well as the unaffected side until the end of the growth phase is mandatory due to the risk of residual dysplasia. PMID- 25116242 TI - [Epiphyseolysis of the femoral head: new aspects of diagnostics and therapy]. AB - BACKGROUND: Slipped capital femoral epiphysis (SCFE) is the most common hip disease in adolescents and is always surgically treated with the aim to avoid further slippage and to reduce the risk of degenerative arthritis at young age. OBJECTIVES: A summary of the etiology, pathogenesis, clinical features, radiographic imaging and current therapy concepts is given. MATERIAL AND METHODS: A selective review of the literature was performed. RESULTS: With an increasing body mass index in adolescents the incidence of SCFE also increases. The diagnostic routine is comprised of a clinical examination with the evaluation of Drehmann's sign and a radiographic evaluation including anterior-posterior aspect and frog's legs view. In situ stabilization with a single screw is the standard treatment for the most prevalent mild or moderate stable slippages. In cases of acute slippage a gentle reduction maneuver may be attempted. Hardware removal must not be performed before epiphyseal closure. Common bilateral but not simultaneous occurrence of the disease requires prophylactic pinning of the unaffected side by default, at least in central Europe. Various surgical treatment options exist to reduce the femoroacetabular impingement caused by the slippage. CONCLUSIONS: Current treatment algorithms result in satisfactory long term outcomes. If the risk of developing degenerative arthritis after SCFE may be reduced even more with modern arthroscopic or open surgical procedures to restore the anatomic pre-slip conditions has to be confirmed through further long-term studies. The implementation of programs to prevent obesity in adolescents may also reduce the incidence of SCFE. PMID- 25116243 TI - [Aseptic osteonecrosis in children and adolescents]. AB - BACKGROUND: Aseptic osteonecrosis (AO) in children and adolescents has been described in all parts of the skeleton. The disease is presumed to be caused by local blood circulation disorders, the reasons for which are multifactorial and occur more often in times of stronger growth intensity. DISEASE SEQUELAE: The disease leads to bone catabolism which can affect the epiphyses, metaphyses, apophyses, carpal and tarsal bones of the hands and feet. The more stretched the form alteration of the bone at the end of the diseases is, the earlier arthritic alterations occur due to the incongruence of the corresponding joint partner. If a growth plate is affected, a growth disorder can be the result. DIAGNOSTICS AND THERAPY: The diagnostics and therapeutic measures are oriented to the site and extent of the disease and the age of the child. For early forms of AO magnetic resonance imaging (MRI) is the imaging method of choice. In recent years the medicinal therapy of AO has been described as an additional option. The disease lasts at least several months up to years and more commonly affects boys than girls with the exception of necrosis of the foot tarsals. CONCLUSION: The early diagnosis and immediate initiation of adequate therapy which must take the age and stage of the disease into consideration, can reduce a possible joint destruction. Prostaglandin therapy, as an off label use, leads to a reduction of pain and improvement in mobility. PMID- 25116239 TI - Whole-genome sequencing of individuals from a founder population identifies candidate genes for asthma. AB - Asthma is a complex genetic disease caused by a combination of genetic and environmental risk factors. We sought to test classes of genetic variants largely missed by genome-wide association studies (GWAS), including copy number variants (CNVs) and low-frequency variants, by performing whole-genome sequencing (WGS) on 16 individuals from asthma-enriched and asthma-depleted families. The samples were obtained from an extended 13-generation Hutterite pedigree with reduced genetic heterogeneity due to a small founding gene pool and reduced environmental heterogeneity as a result of a communal lifestyle. We sequenced each individual to an average depth of 13-fold, generated a comprehensive catalog of genetic variants, and tested the most severe mutations for association with asthma. We identified and validated 1960 CNVs, 19 nonsense or splice-site single nucleotide variants (SNVs), and 18 insertions or deletions that were out of frame. As follow up, we performed targeted sequencing of 16 genes in 837 cases and 540 controls of Puerto Rican ancestry and found that controls carry a significantly higher burden of mutations in IL27RA (2.0% of controls; 0.23% of cases; nominal p = 0.004; Bonferroni p = 0.21). We also genotyped 593 CNVs in 1199 Hutterite individuals. We identified a nominally significant association (p = 0.03; Odds ratio (OR) = 3.13) between a 6 kbp deletion in an intron of NEDD4L and increased risk of asthma. We genotyped this deletion in an additional 4787 non-Hutterite individuals (nominal p = 0.056; OR = 1.69). NEDD4L is expressed in bronchial epithelial cells, and conditional knockout of this gene in the lung in mice leads to severe inflammation and mucus accumulation. Our study represents one of the early instances of applying WGS to complex disease with a large environmental component and demonstrates how WGS can identify risk variants, including CNVs and low-frequency variants, largely untested in GWAS. PMID- 25116244 TI - [Chronic knee pain in children and adolescents: review of anatomical and overload related knee pain]. AB - BACKGROUND: Knee pain in children and adolescents is a common reason for presentation in pediatric orthopedic consultation. The causes are manifold and require a thorough patient history, detailed physical examination and extensive diagnostics. DIAGNOSTICS: Chronic knee pain in children and adolescents is a diagnosis by exclusion. An extensive patient history including training habits, pain localization and clinical examination provide indications vital for the diagnosis. Overuse is often the trigger. In dynamic investigations consideration should be given to muscle imbalance. Imaging techniques have a high sensitivity and specificity only in combination with the anamnesis and clinical findings. THERAPY: With pain therapy, targeted physiotherapy, a break in active sport or training modifications, the prognosis is good for overload syndromes. An operative therapy after unsuccessful conservative therapy is necessary in only a few cases. Among the anatomy-related types of knee pain primary popliteal cysts mostly require no therapy and for plica syndrome arthroscopic resection should only be necessary if conservative treatment is unsuccessful. Operative therapy is necessary for symptomatic discoid meniscus. PMID- 25116245 TI - [Osteogenesis imperfecta]. AB - BACKGROUND: Osteogenesis imperfecta (OI) is the most common genetic disease of bone and is characterized by fragile bones and growth disorders of varying severity. Most cases of OI are inherited autosomal dominant and caused by a mutation in the collagen type I gene. DIAGNOSTICS: Indications for OI are bone fragility, stunted growth, scoliosis, skull deformities, blue sclera, loss of hearing, dentinogenesis imperfecta and increased laxity of ligaments and skin. In most cases it is possible to make a clinical diagnosis but a skin biopsy or genetic testing can be useful; however, negative results for these tests do not exclude OI. THERAPY: Therapy must be carried out in a multidisciplinary team and includes conservative (e.g. physiotherapy, rehabilitation programs and orthopedic aids), operative (e.g. intramedullary stabilization procedures) and pharmaceutical (e.g. biphosphonates and growth hormones) procedures. PROGNOSIS: The prognosis depends on the type of OI and ranges from normal life expectations for type 1 patients up to up to perinatal mortality for type II patients. PMID- 25116246 TI - [Differences between short stem prostheses]. AB - The short stem designs currently available are significantly different and can be differentiated into neck containing, partial containing and neck resection designs. In this article, the differences in the design features are presented. These include the differences in the technique of implantation, the significant differences in the reproducibility of the given anatomy of the patient and also concerning their osteologic competence. PMID- 25116247 TI - [Thromboprophylaxis and platelet aggregation inhibitors in spinal surgery: perioperative management]. AB - BACKGROUND: The perioperative use of anticoagulants (AC) and platelet aggregation inhibitors (PAI) in the field of spinal surgery suggests an increased rate of epidural bleeding. However, evidence is lacking and these medications are most often indispensable in the prevention of thromboembolic complications. Comprehensive recommendations for the correct use of AC and PAI are lacking. OBJECTIVE: The aim of this study was an analysis of the current situation with regards to the use of AC and PAI in spinal surgery and development of new recommendations. MATERIAL AND METHODS: Two independent surveys on the perioperative use of AC and PAI were obtained from centers for spinal surgery in Germany. The study obtained information on the perioperative use of AC and PAI, risk assessment of thromboembolic and hemorrhagic events as well as on the type and extent of the substance groups used. RESULTS: Almost the entire patient collective (98%) received perioperative low molecular weight heparin. In 64% the medical prophylaxis was started before surgery and in 36% after surgery. The period of prophylaxis was determined arbitrarily. Approximately 40% of interviewees employed paravertebral infiltration and 19% injected into the epidural space in patients on PAI medication. Open spinal canal surgery was performed in 30% of PAI medicated patients and closed spinal canal surgery was executed in 40%. The risk assessment of PAI differed significantly between aspirin and receptor blocker medication as well as dual administration of PAI. DISCUSSION: The use of AC and PAI in spinal surgery in Germany is very heterogeneous and large deviations from the guidelines frequently occurred. Therefore, there is a strong need for further studies to accurately assess the perioperative use of AC and PAI and to formulate precise recommendations. PMID- 25116248 TI - Expectancy effects during response selection modulate attentional selection and inhibitory control networks. AB - Choosing the correct response from a subset of alternatives is a fundamental problem and particularly demanding where conflicting response tendencies are evident. One phenomenon in this context is the congruency sequence-(Gratton effect), for which different theoretical explanations have been put forward. A critical aspect that differs between these explanations is the expectancy of what will happen in forthcoming trials. In the current study we examine the relevance of expectancy for sequence congruency effects and related neurophysiological processes using a flanker task in which we manipulate the probability that the n+1 trial presents the same stimulus-response mapping than the n trial. We ask what cognitive subprocesses involved in response selection may be modulated by expectancy effects. To distinguish different subprocesses probably modulated by expectancy effects we use event-related potentials (ERPs) in combination with source localization techniques. The data show that cognitive subprocesses modulated by expectancy depend on the nature of expected transitions between succeeding trials. Expectancy effects only affected trial transitions within the same category (i.e., 'compatible-compatible' and 'incompatible-incompatible'), but not between compatibility categories (i.e., 'compatible-incompatible' and 'incompatible-compatible'). On compatible trial transitions attentional selection processes operating via the precuneus mediated expectancy effects, while on incompatible trial transitions inhibitory processes were modulated that were mediated via the medial and middle frontal gyrus, the orbitofrontal cortex, the insular and the parahippocampal gyrus. Conflict monitoring processes per se were not modulated by expectancy effects. The data shows that there are different subprocesses underlying the influence of expectancy on sequence effects during response selection. PMID- 25116250 TI - Genetic variability in the human cannabinoid receptor 1 is associated with resting state EEG theta power in humans. AB - It has long been postulated that exogenous cannabinoids have a profound effect on human cognitive functioning. These cannabinoid effects are thought to depend, at least in parts, on alterations of phase-locking of local field potential neuronal firing. The latter can be measured as activity in the theta frequency band (4 7Hz) by electroencephalogram. Theta oscillations are supposed to serve as a mechanism in neural representations of behaviorally relevant information. However, it remains unknown whether variability in endogenous cannabinoid activity is involved in theta rhythms and therefore, may serve as an individual differences index of human cognitive functioning. To clarify this issue, we recorded resting state EEG activity in 164 healthy human subjects and extracted EEG power across frequency bands (delta, theta, alpha, and beta). To assess variability in the endocannabinoid system, two genetic polymorphisms (rs1049353, rs2180619) within the cannabinoid receptor 1 (CB1) were determined in all participants. As expected, we observed significant effects of rs1049353 on EEG power in the theta band at frontal, central and parietal electrode regions. Crucially, these effects were specific for the theta band, with no effects on activity in the other frequency bands. Rs2180619 showed no significant associations with theta power after Bonferroni correction. Taken together, we provide novel evidence in humans showing that genetic variability in the cannabinoid receptor 1 is associated with resting state EEG power in the theta frequency band. This extends prior findings of exogenous cannabinoid effects on theta power to the endogenous cannabinoid system. PMID- 25116249 TI - Deletion of KCC3 in parvalbumin neurons leads to locomotor deficit in a conditional mouse model of peripheral neuropathy associated with agenesis of the corpus callosum. AB - Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC or ACCPN) is an autosomal recessive disease caused by the disruption of the SLC12A6 gene, which encodes the K-Cl cotransporter-3 (KCC3). A ubiquitous deletion of KCC3 in mice leads to severe locomotor deficits similar to ACCPN patients. However, the underlying pathological mechanism leading to the disease remains unclear. Even though a recent study suggests that the neuropathic features of ACCPN are mostly due to neuronal loss of KCC3, the specific cell type responsible for the disease is still unknown. Here we established four tissue specific KCC3 knockout mouse lines to explore the cell population origin of ACCPN. Our results showed that the loss of KCC3 in parvalbumin-positive neurons led to significant locomotor deficit, suggesting a crucial role of these neurons in the development of the locomotor deficit. Interestingly, mice in which KCC3 deletion was driven by the neuron-specific enolase (NSE) did not develop any phenotype. Furthermore, we demonstrated that nociceptive neurons targeted with Nav1.8-driven CRE and Schwann cells targeted with a desert hedgehog-driven CRE were not involved in the development of ACCPN. Together, these results establish that the parvalbumin-positive neuronal population is an important player in the pathogenic development of ACCPN. PMID- 25116251 TI - Neuropeptide AF induces anxiety-like and antidepressant-like behavior in mice. AB - Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlying neurotransmissions in mice. In order to determine whether there are species differences between rats and mice, we have investigated the action of NPAF on anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and an elevated plus maze test (EPMT) were used to investigate the depression and anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior to the tests. In the mFST, the animals were pretreated with a non-selective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor antagonist, haloperidol, a alpha1/alpha2beta-adrenergic receptor antagonist, prazosin or a non-selective beta-adrenergic receptor antagonist, propranolol 30min before the NPAF administration. In the mFST, NPAF decreased the immobility time and increased the climbing and swimming times. This action was reversed completely by methysergide and partially by atropine, whereas cyproheptadine, haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF decreased the time spent in the arms (open/open+closed). Our results demonstrate that NPAF induces anti-depressant-like behavior in mice, which is mediated, at least in part, through 5HT2-serotonergic and muscarinic cholinergic neurotransmissions. In addition, the NPAF-induced anxiety is species-independent, since it develops also in mice. PMID- 25116252 TI - Gait analysis and the cumulative gait index (CGI): Translational tools to assess impairments exhibited by rats with olivocerebellar ataxia. AB - Deviations from 'normal' locomotion exhibited by humans and laboratory animals may be determined using automated systems that capture both temporal and spatial gait parameters. Although many measures generated by these systems are unrelated and independent, some may be related and dependent, representing redundant assessments of function. To investigate this possibility, a treadmill-based system was used to capture gait parameters from normal and ataxic rats, and a multivariate analysis was conducted to determine deviations from normal. Rats were trained on the treadmill at two speeds, and gait parameters were generated prior to and following lesions of the olivocerebellar pathway. Control (non lesioned) animals exhibited stable hindlimb gait parameters across assessments at each speed. Lesioned animals exhibited alterations in multiple hindlimb gait parameters, characterized by significant increases in stride frequency, braking duration, stance width, step angle, and paw angle and decreases in stride, stance, swing and propulsion durations, stride length and paw area. A principal component analysis of initial hindlimb measures indicated three uncorrelated factors mediating performance, termed Rhythmicity, Thrust and Contact. Deviation in the performance of each animal from the group mean was determined for each factor and values summed to yield the cumulative gait index (CGI), a single value reflecting variation within the group. The CGI for lesioned animals increased 2.3 fold relative to unlesioned animals. This study characterizes gait alterations in laboratory rats rendered ataxic by destruction of the climbing fiber pathway innervating Purkinje cells and demonstrates that a single index can be used to describe overall gait impairments. PMID- 25116253 TI - Periaqueductal gray MU and kappa opioid receptors determine behavioral selection from maternal to predatory behavior in lactating rats. AB - Every mother must optimize her time between caring for her young and her subsistence. The rostro lateral portion of the periaqueductal grey (rlPAG) is a critical site that modulates the switch between maternal and predatory behavior. Opioids play multiple roles in both maternal behavior and this switching process. The present study used a pharmacological approach to evaluate the functional role of rlPAG MU and kappa opioid receptors in behavioral selection. Rat dams were implanted with a guide cannula in the rlPAG and divided into three experiments in which we tested the role of opioid agonists (Experiment 1), the influence of MU and kappa opioid receptor blockade in the presence of morphine (Experiment 2), and the influence of MU and kappa opioid receptor blockade (Experiment 3). After behavioral test, in Experiment 4, we evaluated rlPAG MU and kappa receptor activation in all Experiments 1-3. The results showed that massive opioidergic activation induced by morphine in the rlPAG inhibited maternal behavior without interfering with predatory hunting. No behavioral changes and no receptor activation were promoted by the specific agonist alone. However, kappa receptor blockade increased hunting behavior and increased the level of MU receptor activation in the rlPAG. Thus, endogenous opioidergic tone might be modulated by a functional interaction between opioid receptor subtypes. Such a compensatory receptor interaction appears to be relevant for behavioral selection among motivated behaviors. These findings indicate a role for multiple opioid receptor interactions in the modulation of behavioral selection between maternal and predatory behaviors in the PAG. PMID- 25116254 TI - Re: 'The impact of chronic kidney disease on postoperative outcome following colorectal cancer surgery'. PMID- 25116255 TI - Synthesis and Antimicrobial Activity of 5-(morpholinosulfonyl)isatin Derivatives Incorporating a Thiazole Moiety. AB - This article describes the synthesis of novel 5-(morpholinosulfonyl)isatin derivatives having biologically active thiazole moiety were synthesized via 2 synthetic routes. The first route involved interaction of 5-(morpholino-sulfonyl) isatin with aminothiazole derivatives to give the Schiff's base derivatives (2, 3). The second route involved preparation of thiosemicarbazones (4-7) by treatment of 5-(morpholino- sulfonyl) isatin with thiosemicarbazides followed by cycloalkylation of the products with halogenated compounds to give the thiazole derivatives (8-19). Most of the synthesized compounds were screened against Gram (+), Gram (-) bacterial and fungi. The best gram positive activity was displayed by compounds 1, 13, 14, 15, 16 and 18 and the best gram negative bacteria was showed by compounds 1, 12, 13, 15, and 19, whereas compounds 1, 12, 13, 15, and 19 exhibited the best antifungal activity. PMID- 25116256 TI - Synthesis and characterization of some substituted 3, 4-dihydronaphthalene derivatives through different enaminones as potent cytotoxic agents. AB - A new series of novel substituted 3,4-dihydronaphthalene incorporated to benzo[h]quinoline, benzo[g]indazole, thiazolidin-4-one, pyrazolo[3,4-d]thiazol and thiazolo[4,5-b]pyridine ring systems were synthesized and evaluated for their cytotoxicity against selected human cancer cell lines. Some of the tested compounds exhibited promising carcinoma growth inhibition. The detailed synthesis, spectroscopic data and biological activities of the tested compounds were reported. PMID- 25116257 TI - Comparison of paper- and web-based dietary records: a pilot study. AB - BACKGROUND/AIMS: Paper-based dietary records (Paper-DR) can be replaced by web based dietary records (Web-DR) in both epidemiological studies and clinical practice to reduce the time and logistic burden. We aimed to compare Paper-DR and Web-DR. METHODS: We compared the matching of different food items (n = 1,103) from Paper-DR and Web-DR for energy and 48 nutrients among 16 pregnant volunteers, with DR for the same individuals matched for the same 4 days. Paper DR were coded into the web-based version (referred to as Paper-Web-DR) independently by the same research dietitian. The Wilcoxon signed-rank test comparing mean rank differences, Spearman's rho to measure associations and Bland Altman limits of agreement to evaluate the level of agreement between the two dietary methods across the range of parameters were used. Volunteers also completed an evaluation questionnaire regarding the user acceptability of Paper DR and Web-DR. RESULTS: A high correlation between Paper-DR and Web-DR was noted. There were statistically insignificant differences among 45 nutrients, except for free sugars (p < 0.001), alpha-linolenic acid (p = 0.041), folate (p = 0.036) and pantothenic acid (p = 0.023). Volunteers found the Paper-DR equally time consuming as the Web-DR. The majority of the volunteers (75%) preferred the Web DR. CONCLUSIONS: Paper-DR and Web-DR were comparable across a range of nutritional parameters, with a few exceptions. The Web-DR was more convenient for the majority and has substantial logistic and cost advantages. PMID- 25116258 TI - Gene expression profiling analysis of locus coeruleus in idiopathic Parkinson's disease by bioinformatics. AB - This study aimed to explore the underlying molecular mechanisms of idiopathic Parkinson's disease (IPD) by bioinformatics analysis. Gene expression profile GSE34516 was downloaded from the Gene Expression Omnibus. Eight locus coeruleus post-mortem tissue samples derived from four IPD patients and four neurological healthy controls were used to identify the differentially expressed genes (DEGs) by paired t test. Based on the DEGs, principal components were analyzed. The Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway analysis of the genome microarray data were then performed. Finally, protein-protein interaction (PPI) network of the DEGs was constructed. Total 261 DEGs including 195 up-regulated and 66 down-regulated DEGs were identified. Intracellular protein transport and RNA splicing via transesterification reactions were selected as the most two significantly enriched functions. Mismatch repair, N glycan biosynthesis, spliceosome and nucleotide excision repair were the significantly enriched pathways. In the PPI network, CTSS, CD53, IGSF6, PTPRC and LAPTM5 were the hub nodes. Intracellular protein transport and RNA splicing via transesterification reactions were closely associated with IPD. The DEGs, such as CX3CR1, SLC5A7, CD53 and PTPRC may be the potential targets for IPD diagnosis and treatment. PMID- 25116259 TI - Taste impairment in Miller Fisher syndrome. PMID- 25116260 TI - Familiar Mediterranean fever and multiple sclerosis: an unreported association in the Italian population? PMID- 25116262 TI - PRIMO: Precise radiofrequency inference from multiple observations. AB - PURPOSE: This paper presents Precise Radiofrequency Inference from Multiple Observations (PRIMO), a comprehensive reconstruction framework for calibrating MRI systems with parallel transmit and parallel receive radiofrequency capabilities. THEORY AND METHODS: To date, the vast majority of radiofrequency (RF) calibration methods have considered transmit and receive calibration separately, without acknowledging that transmit field calibration sequences measure sufficient data for receive calibration. PRIMO provides a method of extracting both transmit and receive fields from transmit calibration data without presuming knowledge of either. The method is tested for accuracy through simulation, comparison to a gold standard dataset, and is demonstrated on in-vivo data acquired at 3T. RESULTS: PRIMO is shown to produce RF fields faithful to the gold standard with errors of less than 3% in realistic noise conditions. The in vivo reconstructions demonstrate the method's ability to produce high quality transmit and receive maps, with an 8 transmit/8 receive channel system being fully calibrated in three dimensions in approximately 2 minutes. CONCLUSION: PRIMO provides a unified framework for estimating all transmit and receive fields in a single calibration step. This is becoming increasingly relevant in an era of MRI systems with highly parallel RF architectures. PMID- 25116264 TI - Oxidation of reduced sulfur species: carbon disulfide. AB - A detailed chemical kinetic model for oxidation of CS2 has been developed, on the basis of ab initio calculations for key reactions, including CS2 + O2 and CS + O2, and data from literature. The mechanism has been evaluated against experimental results from static reactors, flow reactors, and shock tubes. The CS2 + O2 reaction forms OCS + SO, with the lowest energy path involving crossing from the triplet to the singlet surface. For CS + O2, which yields OCS + O, we found a high barrier to reaction, causing this step to be important only at elevated temperatures. The model predicts low temperature ignition delays and explosion limits accurately, whereas at higher temperatures it appears to overpredict both the induction time for CS2 oxidation and the formation rate of [O] upon ignition. The predictive capability of the model depends on the accuracy of the rate constant for the initiation step CS2 + O2, which is difficult to calculate due to the intersystem crossing, and the branching fraction for CS2 + O, which is measured only at low temperatures. The governing reaction mechanisms are outlined on the basis of calculations with the kinetic model. PMID- 25116261 TI - The tumor-educated-macrophage increase of malignancy of human pancreatic cancer is prevented by zoledronic acid. AB - We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as "tumor-educated-macrophages" (Edu) and macrophages harvested from mice without tumors as "naive-macrophages" (Naive), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naive-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naive-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P<0.001) compared to cultured cancer cells treated with the conditioned medium from Naive. The mitotic index of the XPA1 cells, expressing GFP in the nucleus and RFP in the cytoplasm, significantly increased in vivo in the presence of Edu- compared to Naive-macrophages (P = 0.001). Zoledronic acid (ZA) killed both Edu and Naive in vitro. Edu promoted tumor growth and metastasis in an orthotopic mouse model of the XPA1 human pancreatic cancer cell line. ZA reduced primary tumor growth (P = 0.006) and prevented metastasis (P = 0.025) promoted by Edu-macrophages. These results indicate that ZA inhibits enhanced primary tumor growth and metastasis of human pancreatic cancer induced by Edu-macrophages. PMID- 25116266 TI - First total synthesis of antihypertensive natural products S-(+)-XJP and R-(-) XJP. AB - The first asymmetric total synthesis of antihypertensive natural products S-(+) XJP and R-(-)-XJP has been achieved in 8 steps starting from commercially available 6-bromo-2-hydroxy-3-methoxybenzaldehyde. Key steps included intramolecular Heck reaction and oxidative ozonolysis reaction with the retention of stereochemistry. A latent functionality strategy was implemented to circumvent the racemization in this endeavor. The protocol described here provided a fast and easily accessible synthetic method to obtain optically pure isochroman-4-one derivatives. Furthermore, the in vivo antihypertensive effects of (+/-)-XJP, S (+)-XJP and R-(-)-XJP were investigated on spontaneously hypertensive rats. The obtained results could provide valuable information to identify a promising lead for further chemical modification research. PMID- 25116265 TI - Frequent words do not break continuous flash suppression differently from infrequent or nonexistent words: implications for semantic processing of words in the absence of awareness. AB - Continuous flash suppression (CFS) has been used as a paradigm to probe the extent to which word stimuli are processed in the absence of awareness. In the two experiments reported here, no evidence is obtained that word stimuli are processed up to the semantic level when suppressed through CFS. In Experiment 1, word stimuli did not break suppression faster than their pseudo-word variants nor was suppression time modulated by word frequency. Experiment 2 replicated these findings, but more critically showed that differential effects can be obtained with this paradigm using a simpler stimulus. In addition, pixel density of the stimuli did prove to be related to suppression time in both experiments, indicating that the paradigm is sensitive to differences in detectability. A third and final experiment replicated the well-known face inversion effect using the same set-up as Experiments 1 and 2, thereby demonstrating that the employed methodology can capture more high-level effects as well. These results are discussed in the context of previous evidence on unconscious semantic processing and two potential explanations are advanced. Specifically, it is argued that CFS might act at a level too low in the visual system for high-level effects to be observed or that the widely used breaking CFS paradigm is merely ill-suited to capture effects in the context of words. PMID- 25116267 TI - Electronic structure study of Ce1-xAxO2 (A = Zr & Hf) nanoparticles: NEXAFS and EXAFS investigations. AB - Single phase nanoparticles (NPs) of CeO2, Ce0.5Zr0.5O2, Ce0.5Hf0.5O2 and Ce0.5Hf0.25Zr0.25O2 were successfully synthesized by co-precipitation method at constant pH and temperature. The X-ray diffraction results revealed that the additive atoms did not segregate to form secondary phases but led to grain size variation in the NPs. The 10 Dq values in the near edge X-ray absorption fine structure (NEXAFS) spectra at the O K-edge did not vary in the same way as the average grain size was changed for the doped CeO2 NPs. The deconvolution of Ce M5 edge and detailed analysis of O K pre-edge peak have shown the higher Ce(+3)/(Ce(+3) + Ce(+4)) ratio in the Zr- and Hf-doped samples. The local atomic structure around the Ce, Zr and Hf atoms was investigated using extended X-ray absorption fine structure (EXAFS) spectroscopy at Ce K-edge, Zr K-edge and Hf L3 edge, respectively, and the EXAFS data were fitted with the theoretical calculations. The 4f occupancy, Ce(+3)/(Ce(+3) + Ce(+4)) ratio of Ce ions, coordination number of Ce and Ce-Ce/Ce-O bond distances were sensitive to the additive atoms but not explicitly changed according to the grain size variation in the NPs. PMID- 25116268 TI - Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety. AB - OBJECTIVE: To determine the effectiveness and safety of perioperative tranexamic acid use in patients undergoing total hip or knee arthroplasty in the United States. DESIGN: Retrospective cohort study; multilevel multivariable logistic regression models measured the association between tranexamic acid use in the perioperative period and outcomes. SETTING: 510 US hospitals from the claims based Premier Perspective database for 2006-12. PARTICIPANTS: 872,416 patients who had total hip or knee arthroplasty. INTERVENTION: Perioperative intravenous tranexamic acid use by dose categories (none, <= 1000 mg, 2000 mg, and >= 3000 mg). MAIN OUTCOME MEASURES: Allogeneic or autologous transfusion, thromboembolic complications (pulmonary embolism, deep venous thrombosis), acute renal failure, and combined complications (thromboembolic complications, acute renal failure, cerebrovascular events, myocardial infarction, in-hospital mortality). RESULTS: While comparable regarding average age and comorbidity index, patients receiving tranexamic acid (versus those who did not) showed lower rates of allogeneic or autologous transfusion (7.7% v 20.1%), thromboembolic complications (0.6% v 0.8%), acute renal failure (1.2% v 1.6%), and combined complications (1.9% v 2.6%); all P<0.01. In the multilevel models, tranexamic acid dose categories (versus no tranexamic acid use) were associated with significantly (P<0.001) decreased odds for allogeneic or autologous blood transfusions (odds ratio 0.31 to 0.38 by dose category) and no significantly increased risk for complications: thromboembolic complications (odds ratio 0.85 to 1.02), acute renal failure (0.70 to 1.11), and combined complications (0.75 to 0.98). CONCLUSIONS: Tranexamic acid was effective in reducing the need for blood transfusions while not increasing the risk of complications, including thromboembolic events and renal failure. Thus our data provide incremental evidence of the potential effectiveness and safety of tranexamic acid in patients requiring orthopedic surgery. PMID- 25116269 TI - Metastatic rhabdoid meningioma with BRAF V600E mutation and good response to personalized therapy: case report and review of the literature. AB - Rhabdoid meningioma is an aggressive phenotype of meningioma, associated with a poor prognosis. We present a very rare case of high-grade meningioma with rhabdoid features that eventually expressed in a coma state. Comprehensive genomic profiling using a Next Generation Sequencing (NGS) assay revealed three genomic alterations: activating BRAF mutation (V600E), loss of CDKN2A/2B, and APC I1307K. After treatment with BRAF inhibitor (dabrafenib), the child's clinical condition improved progressively. After seven months, an MEK inhibitor was added (trametinib). PMID- 25116270 TI - Summary health statistics for u.s. Adults: national health interview survey, 2004. AB - Objectives-This report presents health statistics from the 2004 National Health Interview Survey for the civilian noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, education, family income, poverty status, health insurance coverage, marital status, place of residence, and region of residence for chronic condition prevalence, health status, functional limitations, health care access and utilization, health behaviors, and human immunodeficiency virus testing. Percentages and percent distributions are presented in both age-adjusted and unadjusted versions. Source of Data-The NHIS is a household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics. In 2004, data were collected for 31,326 adults for the Sample Adult questionnaire. The conditional response rate was 83.8%, and the final response rate was 72.5%. The health information for adults in this report was obtained from one randomly selected adult per family. In very rare instances where the sample adult was not able to respond for him or herself, a proxy was allowed. Highlights-In 2004, 62% of adults 18 years of age or over reported excellent or very good health. Sixty-two percent of adults never participated in any type of vigorous leisure-time physical activity, and 15% of adults did not have a usual place of health care. Twelve percent of adults had been told by a doctor or health professional that they had heart disease, and 22% had been told on two or more visits that they had hypertension. Twenty-one percent of all adults were current smokers, and 21% were former smokers. Based on estimates of body mass index, 35% of adults were overweight and 24% were obese. PMID- 25116272 TI - Quantification of the steric influence of alkylphosphine-sulfonate ligands on polymerization, leading to high-molecular-weight copolymers of ethylene and polar monomers. AB - A series of palladium/alkylphosphine-sulfonate catalysts were synthesized and examined in the homopolymerization of ethylene and the copolymerization of ethylene and polar monomers. Catalysts with alkylphosphine-sulfonate ligands containing sterically demanding alkyl substituents afforded (co)polymers whose molecular weight was increased by up to 2 orders of magnitude relative to polymers obtained from previously reported catalyst systems. The polymer molecular weight was found to be closely correlated to the Sterimol B5 parameter of the alkyl substituents in the alkylphosphine-sulfonate ligands. Thus, the use of bulky alkylphosphine-sulfonate ligands represents an effective and versatile method to prepare high-molecular-weight copolymers of ethylene and various polar monomers, which are difficult to obtain by previously reported methods. PMID- 25116271 TI - IgA kappa/IgA lambda heavy/light chain assessment in the management of patients with IgA myeloma. AB - BACKGROUND: Accurate quantification of immunoglobulin A (IgA) monoclonal immunoglobulins by serum protein electrophoresis (SPEP) can be difficult and can impact the assessment of response among patients with multiple myeloma (MM). Therefore, there is a need to identify new assays that better reflect disease burden and response to treatment, and correlate with patient outcome. IgA Hevylite (HLC) measures IgA kappa and IgA lambda separately and provides precise quantitative measurements of the monoclonal IgA expression and polyclonal-isotype matched suppression. In the current study, the authors assessed the usefulness of these assays in the diagnosis of IgA MM and sought to comment on the prognostic value of the assays. METHODS: A study of 157 patients with IgA MM for whom diagnostic samples were available was performed. HLC measurements were performed on a nephelometer and the results were compared with those of electrophoresis. RESULTS: All presentation sera (100 IgA kappa specimens and 57 IgA lambda specimens) were found to have abnormal IgA HLC ratios (IgA kappa median ratio: 336.2 [range, 8.2-7353] and IgA lambda ratio: 0.011 [range, 0.0003-0.45]). In comparison, SPEP bands were quantifiable in only 105 of 157 samples (67%) (median, 28.5 g/L [range, 2.2 g/L-98 g/L]). Of the total of 157 patients, 12 patients (8%) presented with oligosecretory myeloma (<10 g/L; including 4 patients with nonquantifiable SPEP bands). HLC uniquely allows for the measurement of isotype paired suppression, which was found to be associated with shortened overall survival in the current study. CONCLUSIONS: In the current study, IgA HLC ratios were found to be abnormal in all patients and the assay was able to produce quantifiable results in more MM sera than either SPEP or total IgA, potentially representing a solution to the issue of comigration and oligosecretory MM. These preliminary data require confirmation in larger prospective trials to validate the usefulness of IgA HLC. PMID- 25116273 TI - Modeling and simulation of count data. AB - Count data, or number of events per time interval, are discrete data arising from repeated time to event observations. Their mean count, or piecewise constant event rate, can be evaluated by discrete probability distributions from the Poisson model family. Clinical trial data characterization often involves population count analysis. This tutorial presents the basics and diagnostics of count modeling and simulation in the context of pharmacometrics. Consideration is given to overdispersion, underdispersion, autocorrelation, and inhomogeneity. PMID- 25116275 TI - The psychological impact of infertility and fertility treatment on the male partner. AB - OBJECTIVES: This paper reports the findings of two studies that examined factors predicting infertility distress in male partners within couples with an infertility diagnosis and where the couple was receiving fertility treatment. DESIGN: A cross-sectional design was implemented using a questionnaire battery (The questionnaire battery comprised an inventory of four different standardised questionnaires compiled together into one booklet) compiled from earlier theory building qualitative research conducted by the authors. METHODS: Infertility related distress was examined in relation to a number of psychosocial variables including relationship dynamics, self-esteem, current mental health and attitudes towards idealised masculinity. The questionnaire battery was completed by 167 men undergoing or consulting for fertility treatment. Participants were recruited through Irish fertility clinics (Study 1, n = 111) and through an online survey (Study 2, n = 55). RESULTS: Regression analyses identified four variables that predicted variance in infertility distress in both studies: 'Attitude towards idealised masculinity', 'Mental health', 'Relationship satisfaction' and 'Self esteem'. This finding was found to be robust having controlled for age, time since diagnosis, number of attempts at treatment and diagnostic category (male factor, female factor or mixed factor infertility). ConclusiON: Recommendations for fertility clinics and mental health professionals should be made in relation to managing infertility distress and supporting couples during fertility treatment. PMID- 25116274 TI - Interaction Between Domperidone and Ketoconazole: Toward Prediction of Consequent QTc Prolongation Using Purely In Vitro Information. AB - We aimed to investigate the application of combined mechanistic pharmacokinetic (PK) and pharmacodynamic (PD) modeling and simulation in predicting the domperidone (DOM) triggered pseudo-electrocardiogram modification in the presence of a CYP3A inhibitor, ketoconazole (KETO), using in vitro-in vivo extrapolation. In vitro metabolic and inhibitory data were incorporated into physiologically based pharmacokinetic (PBPK) models within Simcyp to simulate time course of plasma DOM and KETO concentrations when administered alone or in combination with KETO (DOM+KETO). Simulated DOM concentrations in plasma were used to predict changes in gender-specific QTcF (Fridericia correction) intervals within the Cardiac Safety Simulator platform taking into consideration DOM, KETO, and DOM+KETO triggered inhibition of multiple ionic currents in population. Combination of in vitro-in vivo extrapolation, PBPK, and systems pharmacology of electric currents in the heart was able to predict the direction and magnitude of PK and PD changes under coadministration of the two drugs although some disparities were detected. PMID- 25116276 TI - The effect of diabetes mellitus on costs and length of stay in patients with peripheral arterial disease undergoing vascular surgery. AB - OBJECTIVE: To determine the impact of diabetes mellitus (DM) and other comorbidities on length of stay (LOS) and costs in patients with peripheral arterial disease (PAD) admitted to a vascular surgical unit. METHODS: A retrospective study was conducted between January 2011 and July 2012 at a tertiary referral hospital in Sydney. Demographic, laboratory, and operative data were obtained from the Australasian Vascular Audit database and hospital diagnostic-related group (DRG) reports. Patients with confirmed PAD with or without DM requiring hospital admission for a diagnosis of claudication, rest pain, ulcer/gangrene, and infection that required lower limb surgical intervention were included. Associations between LOS, surgical procedure, and DRG were explored. RESULTS: Five hundred and sixty-eight admissions (492 patients) were identified: 292 admissions with PAD and 276 admissions with PAD in conjunction with DM (PADDM). Mean LOS for patients with PAD was 10 +/- 13.7 days compared with 15 +/- 18.2 days for PADDM (p < .01; 95% confidence interval 2.7 8.0). LOS and costs were greatest in patients with PADDM undergoing major amputation (37 +/- 13.7 days; US$42,236; p < .01). Analysis of variance indicated that the best predictors of LOS were the presence of DM, bypass surgery, amputation, chronic kidney disease (CKD) stage V, infection, and emergency admission. Over 18 months, the estimated total inpatient costs associated with lower limb intervention for PAD with and without DM amounted to US$7,598,597. People with DM incurred greater inpatient costs, averaging US$1,912 more per episode of admission and a total of US$528,029 over 18 months. CONCLUSION: The impact of diabetes as a comorbid condition in patients with PAD is significant, both clinically and economically. Factors that predict increased LOS in patients with PAD are DM, bypass surgery, amputation, CKD stage V, infection, and emergency admission. PMID- 25116277 TI - Therapeutic effect of compression stockings versus no compression on isolated superficial vein thrombosis of the legs: a randomized clinical trial. AB - OBJECTIVE/BACKGROUND: Leg compression is considered basic treatment for superficial vein thrombosis (SVT), although scientific proof for its efficacy is lacking. The aim of the study was to evaluate the therapeutic effect of compression stockings on isolated SVT of the legs. METHODS: This was a single center randomized controlled trial. Eighty patients with isolated SVT of the legs were instructed to wear compression stockings (23-32 mmHg) (CG) or no compression (NCG) for 3 weeks. All patients received low molecular weight heparin (LMWH) at prophylactic dosage. Non-steroidal anti-inflammatory drugs (NSAIDs) were allowed. The primary outcome variable was the reduction of pain as assessed by a visual analog scale (VAS) and the Lowenberg test. Secondary outcomes were the consumption of analgesics, thrombus length, skin erythema, D-dimer, and quality of life (QoL). RESULTS: Seventy-three patients completed the study. Clinical symptoms and QoL significantly improved from baseline to day 21 in both groups (p < .001 for VAS, Lowenberg test, thrombus length, and erythema; p < .006 for QoL), and consumption of analgesics and D-dimer significantly decreased (p < .001). There was no significant difference between the groups for all tested variables. At day 7, patients in the CG revealed a significantly faster thrombus regression (p = .02). CONCLUSION: Adding compression stockings for 3 weeks to LMWH and NSAIDs does not bring significant additional benefit in the treatment of isolated SVT. When worn for 1 week, compression stockings stimulate significantly faster thrombus regression. PMID- 25116278 TI - Folic acid functionalized silver nanoparticles with sensitivity and selectivity colorimetric and fluorescent detection for Hg2+ and efficient catalysis. AB - In this research, folic acid functionalized silver nanoparticles (FA-AgNPs) were selected as a colorimetric and a 'turn on' fluorescent sensor for detecting Hg(2+). After being added into Hg(2+), AgNPs can emit stable fluorescence at 440 nm when the excitation wavelength is selected at 275 nm. The absorbance and fluorescence of the FA-AgNPs could reflect the concentration of the Hg(2+) ions. Thus, we developed a simple, sensitive analytical method to detect Hg(2+) based on the colorimetric and fluorescence enhancement of FA-AgNPs. The sensor exhibits two linear response ranges between absorbance and fluorescence intensity with Hg(2+) concentration, respectively. Meanwhile, a detection limit of 1 nM is estimated based on the linear relationship between responses with a concentration of Hg(2+). The high specificity of Hg(2+) with FA-AgNPs interactions provided the excellent selectivity towards detecting Hg(2+) over other metal ions (Pb(2+), Mg(2+), Zn(2+), Ni(2+), Cu(2+), Co(2+), Ca(2+), Mn(2+), Fe(2+), Cd(2+), Ba(2+), Cr(6+) and Cr(3+)). This will provide a simple, effective and multifunctional colorimetric and fluorescent sensor for on-site and real-time Hg(2+) ion detection. The proposed method can be applied to the analysis of trace Hg(2+) in lake water. Additionally, the FA-AgNPs can be used as efficient catalyst for the reduction of 4-nitrophenol and potassium hexacyanoferrate (III). PMID- 25116279 TI - Benzothiazole derivatives augment glucose uptake in skeletal muscle cells and stimulate insulin secretion from pancreatic beta-cells via AMPK activation. AB - Adenosine monophosphate-activated protein kinase (AMPK) has been identified as one of the major targets for antidiabetic drugs. This study describes two AMPK activating agents 2-(benzo[d]thiazol-2-ylmethylthio)-6-ethoxybenzo[d]thiazole and 2-(propylthio)benzo[d]thiazol-6-ol, that increase the rate of glucose uptake in L6 myotubes and also augment glucose-stimulated insulin secretion in INS-1E beta cells and rat islets. We believe that such unique bi-functional compounds can be further used for the development of a new class of antidiabetic drugs. PMID- 25116280 TI - Recycling of carbon dioxide and acetate as lactic acid by the hydrogen-producing bacterium Thermotoga neapolitana. AB - The heterotrophic bacterium Thermotoga neapolitana produces hydrogen by fermentation of sugars. Under capnophilic (carbon dioxide requiring) conditions, the process is preferentially associated with the production of lactic acid, which, as shown herein, is synthesized by reductive carboxylation of acetyl coenzyme A. The enzymatic coupling is dependent on the carbon dioxide stimulated activity of heterotetrameric pyruvate:ferredoxin oxidoreductase. Under the same culture conditions, T. neapolitana also operates the unfavorable synthesis of lactic acid from an exogenous acetate supply. This process, which requires carbon dioxide (or carbonate) and an unknown electron donor, allows for the conversion of carbon dioxide into added-value chemicals without biomass deconstruction. PMID- 25116281 TI - Fouling-tolerant nanofibrous polymer membranes for water treatment. AB - Nafion/polyvinylidene fluoride (PVDF) nanofibrous membranes with electrostatically negative charges on the fiber surface were fabricated via electrospinning with superior water permeability and antifouling behaviors in comparison with the conventional microfiltration membranes. The fiber diameter and the resultant pore size in the nanofibrous membranes were easily controlled through tailoring the properties of the electrospinning solutions. The electrospun Nafion/PVDF nanofibrous membranes revealed high porosities (>80%) and high densities of sulfonate groups on the membrane surface, leading to praiseworthy water permeability. Unexpectedly, the water permeability was observed as proportional to the fiber diameter and pore size in the membrane. The presence of sulfonate groups on the membrane improved the antifouling performance against negatively charged oily foulants. PMID- 25116292 TI - In vivo application of short-lag spatial coherence and harmonic spatial coherence imaging in fetal ultrasound. AB - Fetal scanning is one of the most common applications of ultrasound imaging and serves as a source of vital information about maternal and fetal health. Visualization of clinically relevant structures, however, can be severely compromised in difficult-to-image patients due to poor resolution and the presence of high levels of acoustical noise or clutter. We have developed novel coherence-based beamforming methods called Short-Lag Spatial Coherence (SLSC) imaging and Harmonic Spatial Coherence imaging (HSCI), and applied them to suppress the effects of clutter in fetal imaging. This method is used to create images of the spatial coherence of the backscattered ultrasound as opposed to images of echo magnitude. We present the results of a patient study to assess the benefits of coherence-based beamforming in the context of first trimester fetal exams. Matched fundamental B-mode, SLSC, harmonic B-mode, and HSCI images were generated using raw radio frequency data collected on 11 volunteers in the first trimester of pregnancy. The images were compared for qualitative differences in image texture and target conspicuity as well as using quantitative imaging metrics such as signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast. SLSC and HSCI showed statistically significant improvements across all imaging metrics compared with B-mode and harmonic B-mode, respectively. These improvements were greatest for poor quality B-mode images where contrast of anechoic targets was improved from 15 dB in fundamental B-mode to 27 dB in SLSC and 17 dB in harmonic B-mode to 30 dB in HSCI. CNR improved from 1.4 to 2.5 in the fundamental images and 1.4 to 3.1 in the harmonic case. These results exhibit the potential of coherence-based beamforming to improve image quality and target detectability, especially in high noise environments. PMID- 25116293 TI - Two-dimensional ultrasound and ultrasound elastography imaging of trigger points in women with myofascial pain syndrome treated by acupuncture and electroacupuncture: a double-blinded randomized controlled pilot study. AB - Chronic pain has been often associated with myofascial pain syndrome (MPS), which is determined by myofascial trigger points (MTrP). New features have been tested for MTrP diagnosis. The aim of this study was to evaluate two-dimensional ultrasonography (2D US) and ultrasound elastography (UE) images and elastograms of upper trapezius MTrP during electroacupuncture (EA) and acupuncture (AC) treatment. 24 women participated, aged between 20 and 40 years (M +/- SD = 27.33 +/- 5.05) with a body mass index ranging from 18.03 to 27.59 kg/m2 (22.59 +/- 3.11), a regular menstrual cycle, at least one active MTrP at both right (RTPz) and left trapezius (LTPz) and local or referred pain for up to six months. Subjects were randomized into EA and AC treatment groups and the control sham AC (SHAM) group. Intensity of pain was assessed by visual analogue scale; MTrP mean area and strain ratio (SR) by 2D US and UE. A significant decrease of intensity in general, RTPz, and LTPz pain was observed in the EA group (p = 0.027; p < 0.001; p = 0.005, respectively) and in general pain in the AC group (p < 0.001). Decreased MTrP area in RTPz and LTPz were observed in AC (p < 0.001) and EA groups (RTPz, p = 0.003; LTPz, p = 0.005). Post-treatment SR in RTPz and LTPz was lower than pre-treatment in both treatment groups. 2D US and UE effectively characterized MTrP and surrounding tissue, pointing to the possibility of objective confirmation of subjective EA and AC treatment effects. PMID- 25116295 TI - Effect of partial bladder outlet obstruction and reversal on rabbit bladder physiology and biochemistry: duration of recovery period and severity of function. AB - OBJECTIVES: To use a rabbit model of partial bladder outlet obstruction (BOO) to investigate the point at which obstructive bladder dysfunction becomes irreversible. METHODS: Partial BOO was induced in New Zealand White rabbits. It was then reversed and the rabbits were allowed to recover for 4, 8 or 12 weeks. Both at the time of reversal and at the end of the study, the rabbits were grouped according to bladder decompensation level (mild, intermediate or severe) based on bladder mass (weight). RESULTS: A strong correlation was observed between the production and distribution of collagen and the reduction of smooth muscle contractile function. We found that only in the bladders that were severely decompensated at the time of reversal did collagen levels not decrease. CONCLUSION: The data show that recovery of function after reversal of partial BOO is directly related primarily to collagen levels at the time of reversal. PMID- 25116294 TI - Quality of dying in the ICU: is it worse for patients admitted from the hospital ward compared to those admitted from the emergency department? AB - OBJECTIVE: Although most intensive care unit (ICU) admissions originate in the emergency department (ED), a substantial number of admissions arrive from hospital wards. Patients transferred from the hospital ward often share clinical characteristics with those admitted from the ED, but family expectations may differ. An understanding of the impact of ICU admission source on family perceptions of end-of-life care may help improve patient and family outcomes by identifying those at risk for poor outcomes. DESIGN AND SETTING: This was a cohort study of patients with chronic illness and acute respiratory failure requiring mechanical ventilation who died after admission to an ICU in any of the 14 participating hospitals in the Seattle-Tacoma area between 2003 and 2008 (n = 1,500). MEASUREMENTS: Using regression models adjusted for hospital site and patient-, nurse- and family-level characteristics, we examined associations between ICU admission source (hospital ward vs. ED) and (1) family ratings of satisfaction with ICU care; (2) family and nurse ratings of quality of dying; (3) chart-based indicators of palliative care. MAIN RESULTS: Admission from the hospital ward was associated with lower family ratings of quality of dying [beta 0.90, 95% confidence interval (CI) -1.54, -0.26, p = 0.006] and satisfaction (total score beta -3.97, 95% CI -7.89, -0.05, p = 0.047; satisfaction with care domain score beta -5.40, 95% CI -9.44, -1.36, p = 0.009). Nurses did not report differences in quality of dying. Patients from hospital wards were less likely to have family conferences [odds ratio (OR) 0.68, 95% CI 0.52, 0.88, p = 0.004] or discussion of prognosis in the first 72 h after ICU admission (OR 0.72, 95% CI 0.56, 0.91, p = 0.007) but were more likely to receive spiritual care (OR 1.48, 95% CI 1.14, 1.93, p = 0.003) or have life support withdrawn (OR 1.38, 95% CI 1.04, 1.82, p = 0.025). CONCLUSION: Admission from the hospital ward is associated with family perceptions of a lower quality of dying and less satisfaction with ICU care. Differences in receipt of palliative care suggest that family of patients from the hospital ward receive less communication. Nurse ratings of quality of dying did not significantly differ by ICU admission source, suggesting dissimilarities between family and nurse perspectives. This study identifies a patient population at risk for poor quality palliative and end-of life care. Future studies are needed to identify interventions to improve care for patients who deteriorate on the wards following hospital admission. PMID- 25116296 TI - Asparagus, a love story: healthier eating could be just a false memory away. AB - In two experiments, involving 231 subjects, we planted the suggestion that subjects loved to eat asparagus as children. Relative to controls, subjects receiving the suggestion became more confident that they had loved asparagus the first time they tried it. These new (false) beliefs had consequences for those who formed them, including increased general liking of asparagus, greater desire to eat asparagus in a restaurant setting, and a willingness to pay more for asparagus in the grocery store. Ratings of photographs made after the suggestion reveal that the altered nutritional choices may relate to the fact that the sight of asparagus simply looks more appetizing and appealing. These results demonstrate that adults can be led to believe that they had a positive food related experience as children, and that these false beliefs can have healthy consequences. PMID- 25116297 TI - A role for spatial and nonspatial working memory processes in visual search. AB - Searching a cluttered visual scene for a specific item of interest can take several seconds to perform if the target item is difficult to discriminate from surrounding items. Whether working memory processes are utilized to guide the path of attentional selection during such searches remains under debate. Previous studies have found evidence to support a role for spatial working memory in inefficient search, but the role of nonspatial working memory remains unclear. Here, we directly compared the role of spatial and nonspatial working memory for both an efficient and inefficient search task. In Experiment 1, we used a dual task paradigm to investigate the effect of performing visual search within the retention interval of a spatial working memory task. Importantly, by incorporating two working memory loads (low and high) we were able to make comparisons between dual-task conditions, rather than between dual-task and single-task conditions. This design allows any interference effects observed to be attributed to changes in memory load, rather than to nonspecific effects related to "dual-task" performance. We found that the efficiency of the inefficient search task declined as spatial memory load increased, but that the efficient search task remained efficient. These results suggest that spatial memory plays an important role in inefficient but not efficient search. In Experiment 2, participants performed the same visual search tasks within the retention interval of visually matched spatial and verbal working memory tasks. Critically, we found comparable dual-task interference between inefficient search and both the spatial and nonspatial working memory tasks, indicating that inefficient search recruits working memory processes common to both domains. PMID- 25116298 TI - Does the central bottleneck encompass voluntary selection of hedonically based choices? AB - A large literature on multitasking bottlenecks suggests that people cannot generally make decisions or select responses in two different tasks at the same time. However, these tasks have all involved retrieving preinstructed responses, rather than spontaneously choosing actions based on anticipated hedonic consequences. To assess whether the same bottlenecks encompasses voluntary choices, a gambling decision was utilized as the second of two tasks in a psychological refractory period (PRP) design. Three decision-related factors were identified that affected latency of responding in the gambling task. All proved to be additive with stimulus-onset asynchrony (SOA) in dual-task blocks. The results indicate that making a choice to try to optimize outcomes is subject to the same processing bottleneck as the retrieval of preinstructed responses that has been the mainstay of attention and performance research. PMID- 25116299 TI - Stimulus-related inhibition of task set during task switching. AB - Performance after a shifting of task is supported by the inhibition of the executed task, as revealed by slower reaction times (RTs) on alternating compared to nonalternating task sequences (ABA vs. CBA). In the present study we investigated the role of stimulus processing in the establishment of task inhibition during task switching, irrespective of the response selection process. Comparing performance on AbA and CbA task sequences within a procedure in which the b-task only involved stimulus encoding processes for later comparison but response selection did not occur, we found slower RTs on AbA compared to CbA task sequences. This revealed that inhibition of the executed task can be triggered at the stimulus processing stage of the new task. In accordance, inhibition only emerged when interference between tasks occurred at the stimulus level, due to stimuli having features relevant for both the executed and the upcoming task. PMID- 25116300 TI - Seeing the forest before the trees depends on individual field-dependency characteristics. AB - Numerous studies have demonstrated that the well-known global precedence effect, characterized by a visual bias toward global information, is highly dependent on stimulus characteristics (Kimchi, 1992). Despite the extensive global-local literature, few studies have investigated how interindividual characteristics could affect the global precedence effect. In this framework, we studied the relationship between global-local visual biases and the Group Embedded Figure Test (GEFT), a standardized measure of field dependency. Data from 34 participants were consistent with the idea that an individual's bias toward the global level is linearly related to his or her degree of field dependence. Given the important role that global-local visual skills play during visuospatial tasks, these results have important implications for future research in this area. PMID- 25116301 TI - A comparison of bilateral versus unilateral target and distractor presentation in the remote distractor paradigm. AB - The remote distractor effect (RDE) is a robust finding of an increase in saccade onset latencies (20-40 ms) when a distractor is presented simultaneously with a target, compared to when a target is presented on its own (Walker, Deubel, Schneider, & Findlay, 1997). Distractors presented at fixation produce the largest RDE and the effect decreases as distractors are moved into the periphery. Data from two experiments that contrast with these standard findings are reported. Under bilateral target presentation, larger RDE magnitudes occurred for peripheral than for central distractors, whereas under unilateral presentation, the pattern reversed. The findings are discussed with reference to discrimination processes, attentional factors and current models of oculomotor control. It is suggested that in bilateral target presentation the competition between the distractor and the target results in the programming of a saccade to the distractor, as well as a saccade to the target. Time taken to cancel the saccade to the distractor produces the increased saccade latency for peripheral distractors in that condition. PMID- 25116302 TI - Hindsight bias and the activation of counterfactual mind-sets. AB - Previous research has shown that conditional counterfactuals are positively related to the magnitude of creeping determinism. Unlike previous experiments which show this increased hindsight bias to occur after exceptional antecedents, we investigated another possible factor, namely a prior activation of a counterfactual mind-set. We investigated our prediction using a hypothetical scenario. Prior to reading the hindsight scenario some participants were asked to solve a scrambled-sentence test including conditional counterfactual sentences. Results of two experiments were consistent with our predictions: Participants that solved the scrambled-sentence test perceived the outcome to be more inevitable than participants in a no-outcome control condition and participants in a no-prime control condition. Furthermore, we found that this increase in creeping determinism was mediated by the perceived causal strength of the target antecedent for the occurrence of the outcome, and that the priming-effect did not occur when an unconditional counterfactual mind-set was activated before. The results are interpreted as supporting a causal-model theory of the hindsight bias. PMID- 25116303 TI - Orthographic overlap and category size in unconscious category priming: comment on experiment 1c of Van den Bussche and Reynvoet (2007). AB - Van den Bussche and Reynvoet (2007, Experiment 1) report unconscious priming of comparable magnitude from novel words belonging to small and large categories, evidence that they interpret as demonstrating independence from category size of priming that involves semantic analysis. Three experiments raise the possibility that the findings in Experiment 1c of Van den Bussche and Reynvoet reflect subword processing, not semantic analysis. In Experiments 1 and 2, priming was obtained from primes and targets that shared approximately the same degree of subword features as in Experiment 1c of Van den Bussche and Reynvoet, but no priming occurred when sharing of features was minimized. Experiment 3 demonstrated priming driven by subword features when those features were set in opposition to whole-word meaning. These results indicate that orthographic overlap must be considered a potentially important confound in findings that ostensibly support priming mediated by semantic analysis. PMID- 25116304 TI - Talking about health care: news framing of who is responsible for rising health care costs in the United States. AB - This content analysis examines how the American news media have presented the problem of high and rising health care costs, looking particularly at the question of who is responsible. More specifically, the authors examine how often the media have discussed the 5 major causes of the problem: (a) patients, (b) health care providers, (c) insurance companies, (d) the government, and (e) pharmaceutical companies. Results revealed that patients were most often mentioned as the cause of increasing health care costs. The authors also found that the media's attribution of responsibility to patients has increased over the years. Overall, media coverage of rising health care costs peaked in 1993, 2004, and 2009, suggesting that coverage was influenced by newsworthy events (e.g., the president endorsing legislation or signing a bill into law) that draw the public's attention. PMID- 25116305 TI - Prehospital stroke care: limitations of current interventions and focus on new developments. AB - BACKGROUND: The global burden of stroke is immense, both in medical and economic terms. With the aging population and the ongoing industrialization of the third world, stroke prevalence is expected to increase and will have a major effect on national health expenditures. Currently, the medical treatment for acute ischemic stroke is limited to intravenous recombinant tissue plasminogen activator (IV r tPA), but its time dependency leads to low utilization rates in routine clinical practice. Prehospital delay contributes significantly to delayed or missed treatment opportunities in acute stroke. State-of-the-art acute stroke care, starting in the prehospital phase, could thereby reduce the disease burden and its enormous financial costs. SUMMARY: The first part of this review focuses on current education measures for the general public, the emergency medical services (EMS) dispatchers and paramedics. Although much has been expected of these measures to improve stroke care, no major effects on prehospital delay or missed treatment opportunities have been demonstrated over the years. Most interventional studies showed little or no effect on the onset-to-door time, IV r tPA utilization rates or outcome, except for prenotification of the receiving hospital by the EMS. No data are currently available on the cost-effectiveness of these commonly used measures. In the second part, we discuss new developments for the improvement of prehospital stroke diagnosis and treatment which could open new perspectives in the nearby future. These include the implementation of prehospital telestroke and the deployment of mobile stroke units. These approaches may improve patient care and could serve as a platform for prehospital clinical trials. Other opportunities include the implementation of noninvasive diagnostics (like transcranial ultrasound and blood-borne biomarkers) and the reevaluation of neuroprotective strategies in the prehospital phase. Key Messages: Timely initiation of treatment can effectively reduce the medical and economic burden of stroke and should begin with optimal prehospital stroke care. For this, prehospital telemedicine is a particularly attractive approach because it is a scalable solution that has the potential to rapidly optimize acute stroke care at limited cost. PMID- 25116307 TI - The intricate interplay between RNA viruses and NF-kappaB. AB - RNA viruses have rapidly evolving genomes which often allow cross-species transmission and frequently generate new virus variants with altered pathogenic properties. Therefore infections by RNA viruses are a major threat to human health. The infected host cell detects trace amounts of viral RNA and the last years have revealed common principles in the biochemical mechanisms leading to signal amplification that is required for mounting of a powerful antiviral response. Components of the RNA sensing and signaling machinery such as RIG-I like proteins, MAVS and the inflammasome inducibly form large oligomers or even fibers that exhibit hallmarks of prions. Following a nucleation event triggered by detection of viral RNA, these energetically favorable and irreversible polymerization events trigger signaling cascades leading to the induction of antiviral and inflammatory responses, mediated by interferon and NF-kappaB pathways. Viruses have evolved sophisticated strategies to manipulate these host cell signaling pathways in order to ensure their replication. We will discuss at the examples of influenza and HTLV-1 viruses how a fascinating diversity of biochemical mechanisms is employed by viral proteins to control the NF-kappaB pathway at all levels. PMID- 25116308 TI - [The current legal status of human organ transplantation]. AB - Advances in medical technology mean that organ donation operations hold the potential to significantly improve the health status of organ failure patients. Taiwan registers an average of 100~200 organ donors per year; however, cases awaiting organ transplant regularly number 8,000 annually. According to the Human Organ Transplant Act, health professionals are obliged to promote organ donation. This article introduces the Taiwan Human Organ Transplant Act and illustrates its implementation and relevant provisions in order to increase general awareness among healthcare professionals of the legal aspects of organ donation and transplantation. In addition, this paper cites two judicial decisions that highlight domestic judicial practice with regard to human organ transplantation. These include decisions on AIDS organ donation and the ruling not to establish an organ bank. Healthcare professionals must comprehend the legal requirements and current status of human organ transplantation in order to play a positive role in increasing organ donations in Taiwan. A win-win situation for healthcare provision and patients results when patient safety is the cornerstone of healthcare provider services. PMID- 25116309 TI - [New life from the heart: assessment and management of heart transplant patients]. AB - Patients who receive heart transplantation surgery following end-stage cardiac failure benefit from efforts to improve their post-surgical quality of life. Assessing and managing perioperative care play an important role in heart transplantation. Evaluations of donor and recipient should be conducted carefully and recommended candidates should by vetted by a qualified heart transplantation committee. The operative procedure is different from general cardiac surgery, and organ preservation is a key step in linking the donor to the recipient. Postoperative infection control and administration of immunosuppressive agents further affect the outcome of heart transplantation. Based on a review of articles and our clinical care experience, we focus on the assessment and the management of heart transplantation in this article. PMID- 25116310 TI - [Current management and care issues in kidney transplant recipients]. AB - Kidney transplantation is one strategy for treating end-stage renal disease. Recent advances in perioperative management and immunosuppressive agents as well as improved understanding of transplant immunology have improved the post-surgery quality of life of kidney recipients dramatically. However, lifelong monitoring of renal functions and potential complications is essential to ensure optimal medical outcomes. Furthermore, the self-care competency of transplant recipients is a significant factor affecting survival of the graft and the patient over the long term. All kidney transplant recipients should comply with the self-care instructions provided by transplantation medical personnel and work to improve their self-care abilities in order to prevent / detect post-transplant complications such as rejection, infection, and medical comorbidities as early as possible. The purpose of this study is to explore the current management and care issues faced by kidney transplant recipients. PMID- 25116311 TI - [Factors associated with adherence to immunosuppressive therapy among transplant recipients]. AB - Advancing medical technology has made organ transplantation an emerging surgical treatment option for organ failure. Patients who receive transplants must take immunosuppressive agents for the remainder of their life in order to maintain good graft function. Failure to take these agents may affect the function of the transplanted graft, reduce quality of life, and even cause death. Thus, encouraging patients to take immunosuppressive agents as directed is critical to minimizing the long-term medical burdens and social costs of organ transplantation. The purpose of this study is to explore the factors associated with adherence to immunosuppressive therapy among transplant recipients using the WHO adherence model. Findings are provided as a reference to health education and clinical care planners. PMID- 25116306 TI - Macromolecular transport between the nucleus and the cytoplasm: Advances in mechanism and emerging links to disease. AB - Transport of macromolecules between the cytoplasm and the nucleus is critical for the function of all eukaryotic cells. Large macromolecular channels termed nuclear pore complexes that span the nuclear envelope mediate the bidirectional transport of cargoes between the nucleus and cytoplasm. However, the influence of macromolecular trafficking extends past the nuclear pore complex to transcription and RNA processing within the nucleus and signaling pathways that reach into the cytoplasm and beyond. At the Mechanisms of Nuclear Transport biennial meeting held from October 18 to 23, 2013 in Woods Hole, MA, researchers in the field met to report on their recent findings. The work presented highlighted significant advances in understanding nucleocytoplasmic trafficking including how transport receptors and cargoes pass through the nuclear pore complex, the many signaling pathways that impinge on transport pathways, interplay between the nuclear envelope, nuclear pore complexes, and transport pathways, and numerous links between transport pathways and human disease. The goal of this review is to highlight newly emerging themes in nuclear transport and underscore the major questions that are likely to be the focus of future research in the field. PMID- 25116312 TI - [The effects of multimedia-assisted instruction on the skin care learning of nurse aides in long-term care facilities]. AB - BACKGROUND: Skin care is an important responsibility of nurse aides in long-term care facilities, and the nursing knowledge, attitudes, and skills of these aides significantly affects quality of care. However, the work schedule of nurse aides often limits their ability to obtain further education and training. Therefore, developing appropriate and effective training programs for nurse aides is critical to maintaining and improving quality of care in long-term care facilities. PURPOSE: This study investigates the effects of multimedia assisted instruction on the skin care learning of nurse aides working in long-term care facilities. METHODS: A quasi-experimental design and convenient sampling were adopted in this study. Participants included 96 nurse aides recruited from 5 long term care facilities in Taoyuan County, Taiwan. The experimental group received 3 weeks of multimedia assisted instruction. The control group did not receive this instruction. The Skin Care Questionnaire for Nurse Aides in Long-term Care Facilities and the Skin Care Behavior Checklist were used for assessment before and after the intervention. RESULTS: (1) Posttest scores for skin care knowledge, attitudes, behavior, and the skin care checklist were significantly higher than pretest scores for the intervention group. There was no significant difference between pretest and posttest scores for the control group. (2) A covariance analysis of pretest scores for the two groups showed that the experimental group earned significantly higher average scores than their control group peers for skin care knowledge, attitudes, behavior, and the skin care checklist. CONCLUSIONS: The multimedia assisted instruction demonstrated significant and positive effects on the skin care leaning of nurse aides in long-term care facilities. This finding supports the use of multimedia assisted instruction in the education and training of nurse aides in long-term care facilities in the future. PMID- 25116313 TI - [Health networks for new immigrants in taiwan]. AB - BACKGROUND: Healthcare and studies related to new immigrants in Taiwan have been influenced by immigrant reproductive health management policy. Some nursing scholars have criticized the top-down approach as potentially not addressing the actual healthcare needs of these immigrants. Medical institutions are being called upon to provide culturally appropriate care. PURPOSE: Using health networks as its conceptual framework, this paper explores the definition of health as perceived by recent immigrants to Taiwan and their perspectives on seeking and maintaining health. METHODS: This paper uses participant observation and depth-interviews to assess how recent immigrants from Mainland China, Vietnam, and Indonesia seek health in their new homeland, evaluate the differences between the healthcare systems in their former and current countries, and recommend actions necessary to ensure the health and wellbeing of this population. RESULTS: The findings are grouped into three themes: "the differences between immigrants and Taiwanese in health care," "local health networks", and "transnational health networks." These themes reflect the views on health and health care of recent female immigrants to Taiwan. CONCLUSIONS: CONCLUSION: Through the actions and narratives of these immigrants, this paper suggests the priority concerns that immigrant agencies should address in order to maintain the health of this group. Additionally, findings give some insight into the gender and ethnic characteristics of immigrant health networks. Immigrants construct and rely upon social relations, cultural identity, and resources to maintain their wellbeing. This study contributes to transcultural nursing theory and to in service training and helps medical practitioners and nurses provide culturally appropriate care. PMID- 25116314 TI - [The physical activity and life healing in psychiatric patients: taijiguan as an example]. AB - BACKGROUND: Chronic psychiatric patients tend to have cognitive and functional impairments. Participation in physical activity has been shown to improve their health and independence. Regular practice of Taijiquan may help improve mood and life stresses, promoting physical and mental health. PURPOSE: This research explores the effect of a 13-week Taijiquan learning program on the daily life experience of chronic psychiatric patients. The process and the essential meaning of the entire learning experiences are presented. METHODS: Data were collected from a psychiatric daycare center at a Teaching Hospital in Taipei. The 6 patients who participated in this study included 3 with bipolar disorders and 3 with schizophrenia. Narrative inquiry and focus-group interviews were used for qualitative data collection and analysis. RESULTS: The initial results of participant experiences were categorized into 3 themes: 1. Learning kung fu in the Taijiquan; 2. Releasing binding through the practice of Taijiquan; and 3. Pursuit of excellence through the learning of Taijiquan. The views of illness, body, and interpersonal interaction as well as the three stages of dilemma, transcendence / acclimation, and acquaintance for the psychiatric patients and their Taijiquan's learning world were described and the potential therapeutic effects on the body and daily life of these patients were explored. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Learning Taijiquan is highly challenging for the novice, especially those with chronic psychiatric illnesses. However, after familiarization with the postural actions and key concepts of this exercise, Taijiquan facilitated body relaxation, heightened perception, and postural balance. Consequently, this exercise stabilized the mood, disease status, and capacity for handling interpersonal relationships of participants and consequently may enhance their long-term life quality and disease recovery status. Results of this study recommend strongly that Taijiquan be included as a therapeutic activity for psychiatric patients to improve their health, healing, and recovery. PMID- 25116315 TI - [Psychometric testing of the chinese version of the readiness for hospital discharge scale]. AB - BACKGROUND: Little has been published in the literature regarding how patients self-evaluate their degree of readiness for hospital discharge. Furthermore, there is currently no self-evaluation tool available in Chinese able to assess the discharge readiness of patients. PURPOSE: This study was used to psychometrically test the Chinese version of the readiness for hospital discharge scale (RHDS_C). METHODS: This study used a cross-sectional design. Two samples were recruited in a two-stage process at two hospitals in Southern Taiwan. Two hundred and twenty-three patients with a diagnosis of either colorectal cancer or hepatic cancer were used to conduct an exploratory factor analysis (EFA) in the first stage of the study. Another 323 patients with a diagnosis of stroke were used conduct a confirmatory factor analysis (CFA). The instrument used was the Readiness for Hospital Discharge Scale (RHDS) developed by Weiss & Piacentine. RESULTS: RHDS_C consists of three subscales: personal status (4 items), coping ability (4 items), and expected support (4 items) adapted from the CFA. The assessed goodness-of-fit index (GFI = .92, AGFI = .88, NFI = .97) indicate the model fit the data well based upon the CFA. Criterion-related validity was supported by the correlation between the original RHDS and the RHDS_C (r = .96, p < .001). The Cronbach's alpha coefficients were .89 for the overall scale and .73, .90, and .89 for the 3 subscales, respectively. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study confirms the validity of the RHDS_C and suggests this instrument is able to reliably assess the readiness of patients for discharge from the hospital. We recommend the scale be applied in the clinical setting to evaluate the discharge readiness of hospital patients. PMID- 25116316 TI - [A project to reduce the incidence of intubation care errors among foreign health aides]. AB - BACKGROUND & PROBLEMS: Foreign health aides are the main providers of care for the elderly and the physically disabled in Taiwan. Correct care skills improve patient safety. In 2010, the incidence of mistakes among foreign health aides in our hospital unit was 58% for nasogastric tube care and 57% for tracheostomy tube care. A survey of foreign health aides and nurses in the unit identified the main causes of these mistakes as: communication difficulties, inaccurate instructions given to patients, and a lack of standard operating procedures given to the foreign health aides. PURPOSE: This project was designed to reduce the rates of improper nasogastric tube care and improper tracheostomy tube care to 20%, respectively. METHODS: This project implemented several appropriate measures. We produced patient instruction hand-outs in Bahasa Indonesia, established a dedicated file holder for Bahasa Indonesian tube care reference information, produced Bahasa Indonesian tube-care-related posters, produced a short film about tube care in Bahasa Indonesian, and established a standardized operating procedure for tube care in our unit. RESULTS: Between December 15th and 31st, 2011, we audited the performance of a total of 32 foreign health aides for proper execution of nasogastric tube care (21 aides) and of proper execution of tracheostomy tube care (11 aides). Patients with concurrent nasogastric and tracheostomy tubes were inspected separately for each care group. The incidence of improper care decreased from 58% to 18% nasogastric intubation and 57% to 18% for tracheostomy intubation. CONCLUSIONS: This project decreased significantly the incidence of improper tube care by the foreign health aides in our unit. Furthermore, the foreign health aides improved their tube nursing care skills. Therefore, this project improved the quality of patient care. PMID- 25116317 TI - [Reducing the incidence of needlestick injuries due to insulin pen injectors among self-users in the outpatient clinic setting]. AB - BACKGROUND & PROBLEM: The rising number of people practicing insulin self injection at home has led to increasing numbers of needlestick injuries due to inadequate self-injection skills among these patients. To reduce needlestick injuries at home, patients should not recap needles and should adopt proper needle disposal practices. A random survey of 80 outpatients currently using insulin pen injectors at home conducted between February and April 2012 found that 70% self-reported suffering needlestick incidents. Data analysis indicated the principal causes of these incidents were the lack of standard operating procedures, the absence of educational training, the shortage of educational instruction sheets for patients, and the inadequate skills and tools available to patients for disposing of needles safely at home. PURPOSE: The aim of this project was to decrease the needlestick incidence rate for outpatients that use insulin pen injectors in order to increase overall patient safety. RESOLUTION: The project team established a pen injector standard operation procedure (SOP), conducted an educational training program, developed nursing instruction sheets for patients, designed and distributed needle disposal containers to patients, and taught patients the correct techniques for the disposing of needles at home. RESULTS: The needlestick incidence rate decreased from 70% pretest to 2.6% following implementation of the abovementioned measures. CONCLUSIONS: This project effectively reduced the needlestick rate attributable to insulin pen injectors. The authors hope that other departments will adopt this approach in order to improve patient safety. PMID- 25116318 TI - [Consent vs. Assent: Ethical Considerations Related to Bone Marrow Transplantation in Adolescents]. AB - Bone marrow transplantation (BMT) is a frequently considered treatment option for terminal childhood cancer. However, the side effects of BMT frequently cause short- and long-term physical discomfort and spiritual suffering, which significantly impact patient quality of life. In Taiwan, parental consent is typically given priority over the assent of children in medical decisions. This article uses a case of an adolescent patient with neuroblastoma undergoing BMT to discuss the best interest standard and contradictions between the consent of parents and the assent of their children. This article argues that medical staffs are responsible to protect the right of children to fully consider and influence the decisions related to their treatment options. Medical staffs should communicate to parents the importance of their children's assent and promote better communication between parents and their children in order to achieve the best outcome for the family as a whole. When mutual communication is unable to resolve conflicts between parents and their children, we recommend seeking assistance from the ethics committee in the hospital. PMID- 25116319 TI - [Clinical care of lung cancer patients with body image changes after targeted therapy]. AB - Lung cancer has a relatively short survival prognosis and advanced disease progression. Therefore, targeted therapy has become one of the most frequent treatments of this disease. Targeted therapy has several features that effectively extend the survival period; is easy to apply and use; and has fewer side effects than chemotherapy. Therefore, this therapy approach has become the preferred choice of patients with advanced lung cancer. However, current targeted therapies like Iressa and Tarceva produce side effects such as skin dryness and acneiform eruption that may bother patients. These side effects may further cause patient concern over negative changes in their body image, and these concerns may influence their work and social lives. Additionally, some patients treated with targeted therapy worry about their chances of survival if they reduce or stop the medication to avoid the side effects. Consequently, patients may struggle with both physical and psychological impacts, and may have problems sustaining a good quality of life. This article focuses on delivering relevant information to patients receiving targeted therapy who suffer from dermatological toxicity and damage to their body image. We demonstrate an assessment tool and information to help patients cope with physical and psychosocial issues through daily skin care routines, mental / psychological supports, and cognitive behavior therapy. These measures may help patients rebuild a positive self-concept. We plan to develop further associated training to provide professionals / care providers with the appropriate knowledge and skills to care for cancer patients in a resource limited environment so that they may improve the quality of nursing care for patients with body image changes. PMID- 25116320 TI - [Applying Swanson's Caring Theory to Manage Spiritual Distress in a Patient With Terminal Lung Cancer]. AB - This case report shares a nursing experience that applied Swanson's Caring Theory as part of the care regimen for a terminal lung cancer patient suffering from spiritual distress. The nursing care was provided from March 20th to April 25th, 2012. Data were collected through observation and conversation and recorded using sketches and written notes. The nurse assessed the patient's relationships with the self, with others, with the environment, and with God in accordance with Stoll's spiritual interrelatedness hypothesis. Several spiritual distresses were reported. Interventions such as "knowing", "being with", "doing for", "enabling" and "maintaining belief" were applied to manage the patient's spiritual distress and address spiritual needs. This case report is intended to help increase the awareness and sensitivity of nurses to patients' spiritual needs and to help nurses provide effective spiritual care. PMID- 25116325 TI - Flow-compensated intravoxel incoherent motion diffusion imaging. AB - PURPOSE: The pseudo-diffusion coefficient D* in intravoxel incoherent motion (IVIM) imaging was found difficult to seize. Flow-compensated diffusion gradients were used to test the validity of the commonly assumed biexponential limit and to determine not only D*, but also characteristic timescale tau and velocity v of the incoherent motion. THEORY AND METHODS: Bipolar and flow-compensated diffusion gradients were inserted into a flow-compensated single-shot EPI sequence. Images were obtained from a pipe-shaped flow phantom and from healthy volunteers. To calculate the IVIM signal outside the biexponential limit, a formalism based on normalized phase distributions was developed. RESULTS: The flow-compensated diffusion gradients caused less signal attenuation than the bipolar ones. A signal dependence on the duration of the flow-compensated gradients was found at low b-values in the volunteer datasets. The characteristic IVIM parameters were estimated to be v = 4.60 +/- 0.34 mm/s and tau = 144 +/- 10 ms for liver and v = 3.91 +/- 0.54 mm/s and tau = 224 +/- 47 ms for pancreas. CONCLUSION: Our results strongly indicate that the biexponential limit does not adequately model the diffusion signal in liver and pancreas. By using both bipolar and flow compensated diffusion gradients of different duration, the characteristic timescale and velocity of the incoherent motion can be determined. PMID- 25116322 TI - Oral human papillomavirus infection in men might contribute to HPV serology. AB - The prospective Finnish Family HPV Study evaluated the dynamics of human papillomavirus (HPV) infection within families. Here, we focused on HPV serology in men. Seroprevalence at baseline, seroconversion and decay of low-risk (LR) HPV6 and 11, and high risk (HR)-HPV16, 18 and 45 L1 antibodies in 122 men at 12, 24 and 36 months were determined using Luminex-based multiplex HPV serology, and correlated with demographic data. At baseline, seropositivity to HPV6, 11, 16, 18 and 45 was observed in 41.0, 11.5, 23.0, 13.9 and 5.7 % of the men, respectively. In univariate analysis, LR-HPV seropositivity was related to smoking status, history of genital warts and being seropositive to HR-HPV. Oral HR-HPV DNA and baseline LR-HPV seropositivity predicted HR-HPV seropositivity. Seroconversion to HPV6, 11, 16, 18 and 45 antigens during follow-up was found in 24.6, 11.5, 5.7, 5.7 and 0.8 %, respectively. Seroconversion to LR-HPV was negatively related to a higher number of children and oral sex, and positively associated with seroconversion to HR-HPV. In multivariate analysis, the same predictors remained significant except for the number of children. In univariate generalised estimating equations (GEE) for HR-HPV, being seroconverted to LR-HPV was the only predictor, but lost its significance in multivariate analyses. Decay of all HPV L1 antibodies was rare and observed in 0-2 %. The HPV antibody profile in men was dominated by response to HPV6, also showing the highest cumulative seroconversion. Oral HPV infection might affect HPV serology: (1) HPV DNA in oral mucosa is associated with baseline HR-HPV seropositivity and (2) practising oral sex significantly reduces longitudinal seroconversion to HPV6 and/or 11. PMID- 25116326 TI - Interceptive [4 + 1] annulation of in situ generated 1,2-diaza-1,3-dienes with diazo esters: direct access to substituted mono-, bi-, and tricyclic 4,5 dihydropyrazoles. AB - In situ derived acyclic and cyclic 1,2-diaza-1,3-dienes (DDs) were engaged in interceptive [4 + 1] annulation strategy with diazo esters (DEs). The catalytic activity of inexpensive copper(II) chloride allows the direct synthesis of mono-, bi-, and tricyclic 4,5-dihydropyrazole-5-carboxylic acid derivatives in a process that circumvents the use of an anhydrous and inert atmosphere. PMID- 25116321 TI - Retinal dendritic cell recruitment, but not function, was inhibited in MyD88 and TRIF deficient mice. AB - BACKGROUND: Immune system cells are known to affect loss of neurons due to injury or disease. Recruitment of immune cells following retinal/CNS injury has been shown to affect the health and survival of neurons in several models. We detected close, physical contact between dendritic cells and retinal ganglion cells following an optic nerve crush, and sought to understand the underlying mechanisms. METHODS: CD11c-DTR/GFP mice producing a chimeric protein of diphtheria toxin receptor (DTR) and GFP from a transgenic CD11c promoter were used in conjunction with mice deficient in MyD88 and/or TRIF. Retinal ganglion cell injury was induced by an optic nerve crush, and the resulting interactions of the GFPhi cells and retinal ganglion cells were examined. RESULTS: Recruitment of GFPhi dendritic cells to the retina was significantly compromised in MyD88 and TRIF knockout mice. GFPhi dendritic cells played a significant role in clearing fluorescent-labeled retinal ganglion cells post-injury in the CD11c-DTR/GFP mice. In the TRIF and MyD88 deficient mice, the resting level of GFPhi dendritic cells was lower, and their influx was reduced following the optic nerve crush injury. The reduction in GFPhi dendritic cell numbers led to their replacement in the uptake of fluorescent-labeled debris by GFPlo microglia/macrophages. Depletion of GFPhi dendritic cells by treatment with diphtheria toxin also led to their displacement by GFPlo microglia/macrophages, which then assumed close contact with the injured neurons. CONCLUSIONS: The contribution of recruited cells to the injury response was substantial, and regulated by MyD88 and TRIF. However, the presence of these adaptor proteins was not required for interaction with neurons, or the phagocytosis of debris. The data suggested a two-niche model in which resident microglia were maintained at a constant level post-optic nerve crush, while the injury-stimulated recruitment of dendritic cells and macrophages led to their transient appearance in numbers equivalent to or greater than the resident microglia. PMID- 25116328 TI - The CROWN Initiative: journal editors invite researchers to develop core outcomes in women's health. PMID- 25116329 TI - Predictors of non-adherence to follow-up visits and deferasirox chelation therapy among jordanian adolescents with Thalassemia major. AB - Poor adherence to treatment can have negative effects on outcomes and heath care cost. However, little is known about the factors that impact adherence to deferasirox chelation therapy. The aims of this study were to identify rates and predictors of non-adherence to medical regimen among thalassemia major adolescents on deferasirox oral chelation therapy by using subjective (self reporting) and objective (serum ferritin and follow-up visits) measures. Convenient samples of 164 adolescents, aged 12-19 years were recruited from three National Thalassemia Centers in Jordan. Patients were interviewed using a four section questionnaire and the medical records were checked. Results indicated that rate of adherence according to self-report was (73%); while to follow-up medical appointments and serum ferritin level rates was 57% and 47%, respectively. One-third of participant adolescents (n = 52) were psychologically impaired. Multivariate analysis showed that factors affecting adolescent non adherence to deferasirox chelation therapy is different from that affecting adherence to follow-up visits. In general, adolescents more than 16 years old, presence of sibling with thalassemia, lack of parental monitoring, lower family income, decrease frequency of blood transfusion, and psychological impairment were found significant predictors of non-adherence among adolescents. Disease knowledge was not associated with adherence status of the adolescents. Clinician should be aware of high prevalence of low adherence to chelation therapy during adolescent years. Nurses need to regularly assess, monitor, and promote adherence behavior that might impact patients' outcomes. PMID- 25116327 TI - Grouping annotations on the subcellular layered interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line. AB - Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652) between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis. PMID- 25116330 TI - Iridium-catalyzed C-H borylation of pyridines. AB - The iridium-catalysed C-H borylation is a valuable and attractive method for the preparation of aryl and heteroaryl boronates. However, application of this methodology for the preparation of pyridyl and related azinyl boronates can be challenged by low reactivity and propensity for rapid protodeborylation, particularly for a boronate ester ortho to the azinyl nitrogen. Competition experiments have revealed that the low reactivity is due to inhibition of the active catalyst through coordination of the azinyl nitrogen lone pair at the vacant site on the iridium. This effect can be overcome through the incorporation of a substituent at C-2. Moreover, when this is sufficiently electron-withdrawing protodeborylation is sufficiently slowed to permit isolation and purification of the C-6 boronate ester. Following functionalization, reduction of the directing C 2 substituent provides the product arising from formal ortho borylation of an unhindered pyridine ring. PMID- 25116332 TI - Summary health statistics for u.s. Children: national health interview survey, 2011. AB - Objectives-This report presents both age-adjusted and unadjusted statistics from the 2011 National Health Interview Survey (NHIS) on selected health measures for children under age 18 years, classified by sex, age, race, Hispanic origin, family structure, parent education, family income, poverty status, health insurance coverage, place of residence, region, and current health status. Topics included are asthma, allergies, learning disability, attention deficit hyperactivity disorder (ADHD), prescription medication use for at least 3 months, respondent-assessed health status, school days missed due to illness or injury, usual place of health care, time since last contact with a health care professional, selected measures of health care access, emergency room visits, and dental care. Data Source-NHIS is a multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics and is representative of the civilian noninstitutionalized population of the United States. This report analyzes data from two of the main components of NHIS: the family core, in which data are collected for all family members by interviewing an adult family respondent, and the sample child core, in which additional health information is collected about a randomly selected child (the ''sample child'') from an adult proxy familiar with the child's health. Selected Highlights-In 2011, most U.S. children under age 18 years had excellent or very good health (83%). However, 7% of children had no health insurance coverage, and 3% of children had no usual place of health care. Six percent of children had unmet dental need because their families could not afford dental care. Fourteen percent of children had ever been diagnosed with asthma. An estimated 8% of children aged 3-17 had a learning disability, and an estimated 9% of children had ADHD. PMID- 25116331 TI - Prognostic significance of complex karyotype and monosomal karyotype in adult patients with acute lymphoblastic leukemia treated with risk-adapted protocols. AB - BACKGROUND: The karyotype is a predictor of outcomes in adults with acute lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex karyotype (CK) has been reported, whereas the prognostic relevance of monosomal karyotype (MK) has not been consistently evaluated. We aimed to assess the prognostic value of CK and MK in adults with ALL treated with risk-adapted protocols of the Spanish PETHEMA Group. METHODS: The karyotypes of 881 adult ALL patients treated according to the protocols of the PETHEMA Group between 1993 and 2012 were centrally reviewed. CK and MK were assessed according to Moorman's criteria, and Breem's criteria, respectively. Specific analyses according to the risk groups and to the presence of t(9:22) were performed. RESULTS: Of 364 evaluable patients 33 (9.2%) had CK, and 68 of 535 evaluable patients (12.8%) had MK. Complete remission rate, remission duration, and overall survival were not significantly different according to the presence of CK or MK in the whole series, according to the B or T lineage, in the high-risk group, or in patients with t(9;22), regardless of imatinib treatment, and in patients who received chemotherapy alone or chemotherapy followed by stem cell transplantation CONCLUSIONS: Our study shows that CK and MK were not associated with a worse prognosis in adult patients with ALL treated with risk-adapted or subtype oriented protocols. In patients with Ph+ ALL, MK did not have an impact on prognosis irrespective of imatinib treatment. PMID- 25116333 TI - Ordered structure and thermal expansion in tungsten bronze Pb2K(0.5)Li(0.5)Nb5O15. AB - The crystal structure and thermal expansion behaviors of a new tetragonal tungsten bronze (TTB) ferroelectric, Pb2K(0.5)Li(0.5)Nb5O15, were systematically investigated by selected-area electron diffraction (SAED), neutron powder diffraction, synchrotron X-ray diffraction (XRD), and high-temperature XRD. SAED and Rietveld refinement reveal that Pb2K(0.5)Li(0.5)Nb5O15 displays a commensurate superstructure of simple orthorhombic TTB structure at room temperature. The structure can be described with space group Bb21m. The transition to a paraelectric phase (P4/mbm) occurs at 500 degrees C. Compared with Pb2KNb5O15 (PKN), the substitution of 0.5K(+) with small 0.5Li(+) into PKN causes the tilting of NbO6 octahedra away from the c axis with Deltatheta ~ 10 degrees and raises the Curie temperature by 40 degrees C, and the negative thermal expansion coefficient along the polar b axis increases more than 50% in the temperature range 25-500 degrees C. We present that, by introduction of Li(+), the enhanced spontaneous polarization is responsible for the enhanced negative thermal expansion along the b axis, which may be caused by more Pb(2+) in the pentagonal caves. PMID- 25116334 TI - ACE consensus meeting report: culture systems. AB - The UK Association of Clinical Embryologists held a workshop on Culture Systems for assisted conception in Sheffield on 22 May 2013. The meeting was organised in the light of the availability of numerous commercial products for the culture of human preimplantation embryos in vitro and the absence of data comparing the performance of these products. Expert opinions were presented, along with survey data provided by participating IVF Centres. The workshop highlighted the lack of a sound evidence base to support the selection of any one commercial product over another, and raised concerns over the lack of information defining precisely the composition of media, and the potential for adverse long-term effects of such products following their use in assisted conception. PMID- 25116335 TI - Drastic change in China's lakes and reservoirs over the past decades. AB - Using remote sensing images, we provided the first complete picture of freshwater bodies in mainland China. We mapped 89,700 reservoirs, covering about 26,870 km(2) and approximately 185,000 lakes with a surface area of about 82,232 km(2). Despite relatively small surface area, the total estimated storage capacity of reservoirs (794 km(3)) is triple that of lakes (268 km(3)). Further analysis indicates that reservoir construction has made the river systems strongly regulated: only 6% of the assessed river basins are free-flowing; 20% of assessed river basins have enough cumulative reservoir capacity to store more than the entire annual river flow. Despite the existence of 2,721 lakes greater than 1 km(2), we found that about 50 lakes greater than km(2) have formed on the Tibetan Plateau resulting from climate change. More than 350 lakes of >=1 km(2) vanished in four other major lake regions. Although the disappearance of lakes happened in the context of global climate change, it principally reflects the severe anthropogenic impacts on natural lakes, such as, the excessive plundering of water resources on the Inner Mongolia-Xinjiang Plateau and serious destruction (land reclamation and urbanization) on the eastern plains. PMID- 25116337 TI - Humidity effect of domain wall roughening behavior in ferroelectric copolymer thin films. AB - We have demonstrated that domain switching in ferroelectric copolymer films can be significantly affected by humidity. With increasing relative humidity (RH), we observed larger domains with highly irregular boundaries as a result of lateral spreading of the tip-induced electric field that originates from water adsorption. Fractal dimension study of irregular domains reveals that the fractal dimension is higher in cases where the RH is higher. The results show that the RH is one of the major switching parameters in ferroelectric copolymers, and therefore could allow clear understanding with regard to domain switching behavior in the ferroelectric copolymer films under ambient conditions. PMID- 25116336 TI - Arsenic trioxide reactivates proteasome-dependent degradation of mutant p53 protein in cancer cells in part via enhanced expression of Pirh2 E3 ligase. AB - The p53 gene is mutated in more than 50% of human tumors. Mutant p53 exerts an oncogenic function and is often highly expressed in cancer cells due to evasion of proteasome-dependent degradation. Thus, reactivating proteasome-dependent degradation of mutant p53 protein is an attractive strategy for cancer management. Previously, we found that arsenic trioxide (ATO), a drug for acute promyelocytic leukemia, degrades mutant p53 protein through a proteasome pathway. However, it remains unclear what is the E3 ligase that targets mutant p53 for degradation. In current study, we sought to identify an E3 ligase necessary for ATO-mediated degradation of mutant p53. We found that ATO induces expression of Pirh2 E3 ligase at the transcriptional level. We also found that knockdown of Pirh2 inhibits, whereas ectopic expression of Pirh2 enhances, ATO-induced degradation of mutant p53 protein. Furthermore, we found that Pirh2 E3 ligase physically interacts with and targets mutant p53 for polyubiquitination and subsequently proteasomal degradation. Interestingly, we found that ATO cooperates with HSP90 or HDAC inhibitor to promote mutant p53 degradation and growth suppression in tumor cells. Together, these data suggest that ATO promotes mutant p53 degradation in part via induction of the Pirh2-dependent proteasome pathway. PMID- 25116338 TI - Silence that can be dangerous: a vignette study to assess healthcare professionals' likelihood of speaking up about safety concerns. AB - PURPOSE: To investigate the likelihood of speaking up about patient safety in oncology and to clarify the effect of clinical and situational context factors on the likelihood of voicing concerns. PATIENTS AND METHODS: 1013 nurses and doctors in oncology rated four clinical vignettes describing coworkers' errors and rule violations in a self-administered factorial survey (65% response rate). Multiple regression analysis was used to model the likelihood of speaking up as outcome of vignette attributes, responder's evaluations of the situation and personal characteristics. RESULTS: Respondents reported a high likelihood of speaking up about patient safety but the variation between and within types of errors and rule violations was substantial. Staff without managerial function provided significantly higher levels of decision difficulty and discomfort to speak up. Based on the information presented in the vignettes, 74%-96% would speak up towards a supervisor failing to check a prescription, 45%-81% would point a coworker to a missed hand disinfection, 82%-94% would speak up towards nurses who violate a safety rule in medication preparation, and 59%-92% would question a doctor violating a safety rule in lumbar puncture. Several vignette attributes predicted the likelihood of speaking up. Perceived potential harm, anticipated discomfort, and decision difficulty were significant predictors of the likelihood of speaking up. CONCLUSIONS: Clinicians' willingness to speak up about patient safety is considerably affected by contextual factors. Physicians and nurses without managerial function report substantial discomfort with speaking up. Oncology departments should provide staff with clear guidance and trainings on when and how to voice safety concerns. PMID- 25116339 TI - Redox-initiated hydrogel system for detection and real-time imaging of cellulolytic enzyme activity. AB - Understanding the process of biomass degradation by cellulolytic enzymes is of urgent importance for biofuel and chemical production. Optimizing pretreatment conditions and improving enzyme formulations both require assays to quantify saccharification products on solid substrates. Typically, such assays are performed using freely diffusing fluorophores or dyes that measure reducing polysaccharide chain ends. These methods have thus far not allowed spatial localization of hydrolysis activity to specific substrate locations with identifiable morphological features. Here we describe a hydrogel reagent signaling (HyReS) system that amplifies saccharification products and initiates crosslinking of a hydrogel that localizes to locations of cellulose hydrolysis, allowing for imaging of the degradation process in real time. Optical detection of the gel in a rapid parallel format on synthetic and natural pretreated solid substrates was used to quantify activity of T. emersonii and T. reesei enzyme cocktails. When combined with total internal reflection fluorescence microscopy and AFM imaging, the reagent system provided a means to visualize enzyme activity in real-time with high spatial resolution (<2 MUm). These results demonstrate the versatility of the HyReS system in detecting cellulolytic enzyme activity and suggest new opportunities in real-time chemical imaging of biomass depolymerization. PMID- 25116340 TI - Smart composite nanosheets with adaptive optical properties. AB - We report efficient design and facile synthesis of size-tunable organic/inorganic nanosheets, via a straightforward liquid exfoliation-adsorption process, of a near percolating gold (Au) thin film deposited onto a branched polyethylenimine (bPEI) matrix. The nanosheets are stiff enough to sustain their two-dimensional (2D) nature in acidic conditions, yet flexible enough to undergo a perfect reversible shape transformation to 1D nanoscrolls in alkaline conditions. The shape transformations, and associated optical property changes, at different protonation states are monitored by transmission electron microscopy (TEM), atomic force microscopy (AFM), UV-visible spectroscopy and zeta potential measurements. Because of their large surface area, both nanosheets and nanoscrolls could be used as capturing substrates for surface-enhanced Raman scattering (SERS) applications. PMID- 25116341 TI - DNA sequence-dependent photoluminescence enhancement in a cationic conjugated polyelectrolyte. AB - DNA sequence-dependent photoluminescence enhancement is found for a cationic polyelectrolyte complexed with single stranded DNA and described as a result of an interplay between electrostatic attraction and the pi-pi stacking between the polyelectrolyte's backbone and DNA's bases. PMID- 25116342 TI - A trial to extend breast cancer screening may be unethical. PMID- 25116343 TI - Evidence of increased centrally enhanced bladder compliance with ageing in a mouse model. AB - OBJECTIVE: To test the hypothesis that ageing is associated with increasing neurogenic enhancement of bladder filling compliance. MATERIALS AND METHODS: Female B6 mice (aged 2, 12, 22 and 26 months) underwent cystometry while alive and immediately after death. Bladder compliance was calculated from pressure-time data. Pressure data were transformed using Fast Fourier Transform to obtain power spectra of bladder pressure variations attributable to contractile activity during filling in both alive and dead mice. A cut-off frequency (CF) was determined for each mouse, above which any power content would be primarily neurogenic. Compliance and power spectra results were compared among age groups, and correlations sought. RESULTS: A reversible loss of bladder compliance and non voiding contractile (NVC) activity followed abolition of voiding reflexes in female colony mice in all age groups. Bladder filling compliance increased with age in urethane-anaesthetised and post-mortem conditions, and more so in the former. Power below the CF did not significantly vary with age. Neurogenic power increased with age, and significantly correlated with compliance. CONCLUSIONS: An increase in neurogenic power during filling accompanies increased centrally mediated compliance enhancement with age. A bladder control model in which brain processes related to micturition may compensate for age-associated changes; thereby preserving voiding function is suggested. Urinary dysfunction could be viewed as the result of homeostatic failure rather than strictly end-organ pathology. PMID- 25116345 TI - The position of the tibia tubercle in 0 degrees -90 degrees flexion: comparing patients with patella dislocation to healthy volunteers. AB - PURPOSE: The aim of this study was to measure the tibia tubercle trochlea groove distance (TT-TG) as a function of knee flexion. Our hypothesis was that there is a different pattern in healthy volunteers and patients with patella instability (PFI). METHODS: Thirty-six knees of 30 patients with at least one dislocation of the patella and 30 knees of 30 healthy volunteers as control group were analysed with magnetic resonance imaging by three different observers. The TT-TG was measured in steps of 15 degrees between 0 degrees and 90 degrees of knee flexion. Furthermore, the alignment of the leg (MA), the femur torsion (FTor) and the tibia torsion (TTor) was calculated. RESULTS: The TT-TG was higher in patients compared to volunteers and in extension compared to flexion. This difference was statistically significant (p<0.05). Most of the patients with a TT TG above 20 mm in extension showed a high decrease in flexion to normal values. In some patients, this compensating mechanism fails. MA, FTor and TTor were not different in patients and control group (n.s.). CONCLUSION: The TT-TG distance is dynamic and decreased significantly during flexion in knees with PFI and healthy volunteers. However, there were a small number of patients in the PFI group where this compensation mechanism did not work. Therefore, the decision to perform a tibia tubercle osteotomy should not be based on one single measurement in extension or 30 degrees of knee flexion. LEVEL OF EVIDENCE: II. PMID- 25116346 TI - Patellofemoral arthrodesis as pain relief in extreme patella alta. AB - PURPOSE: There is no golden standard management for neglected, chronic patellar tendon rupture as they are fairly rare. Nevertheless, accompanying pain can be highly debilitating. By presenting a case of patellar tendon repair, the exceptional results of a patellofemoral arthrodesis are described. METHODS: A patient presented herself with a sustained patellar tendon rupture which was neglected for several years, causing a complete extensor mechanism dysfunction. Her most debilitating complaint was pain. As ligament reconstruction in this case was not possible, patellofemoral arthrodesis was aimed for. The pain resulting from micromotions was subsided by implementing a unique technique using a lock key principle to obtain a patellofemoral arthrodesis. RESULTS: The procedure proceeded without complications. The patient followed a regular post-operative plan and is now successful in maximum weight bearing her knee without pain. CONCLUSIONS: A patellofemoral arthrodesis can be regarded safe and also very effective in the relief of pain in extreme patella alta. LEVEL OF EVIDENCE: Therapeutic studies, Level IV. PMID- 25116347 TI - Rediscovering the patellofemoral joint. PMID- 25116348 TI - Social networks and the communication of norms about prenatal care in rural Mexico. AB - Many normative beliefs are shared and learned through interpersonal communication, yet research on norms typically focuses on their effects rather than the communication that shapes them. This study focused on interpersonal communication during pregnancy to uncover (a) the nature of pregnancy-related communication and (b) normative information transmitted through such communication. Results from interviews with pregnant women living in rural Mexico revealed limited social networks; often, only a woman's mother or the baby's father were consulted about prenatal care decisions. However, women also indicated that communication with others during pregnancy provided important normative information regarding prenatal care. First, most referents believed that women should receive prenatal care (injunctive norm), which was conceptualized by participants as biomedical, nonmedical, or a blend of both. Second, family members often received prenatal care, whereas friends did not (descriptive norms). These findings highlight the key role of personal and social networks in shaping personal pregnancy-related beliefs and behaviors. PMID- 25116349 TI - Parity and short-term estradiol treatment utilizes similar cellular mechanisms to confer protection against breast cancer. AB - BACKGROUND: Protective effect of early pregnancy and short-term estrogen treatment (STET), against breast cancer is well established. The underlying mechanisms are not well understood. In this study, we compared the mammary gland cellular microenvironment influenced/induced by parity and STET alongside age matched controls. METHODS: Parous, STET, and control rats were injected with N methyl-N-nitrosourea at 15 weeks and monitored for the development of mammary cancer. A subset of 4 rats were killed five weeks post carcinogen treatment and mammary gland samples were isolated and subjected to molecular analysis. RESULTS: Our results demonstrated a reduction in cell survival, extracellular matrix associated proliferation, hormonal and growth factor receptor pathways in the experimental groups compared to control rats. Moreover, concomitant reductions in the EMT markers along with cell migration regulators were also observed in parous and STET groups. Hormonal receptor such as GHR, PR, ERalpha and growth factor receptors IGFR, EGFR and erbB2 were down regulated in the treatment groups. Further analysis revealed that parity and STET drastically reduced the expression, activation of JAK2 and nuclear localization of STATs. CONCLUSION: Parity and STET by targeting major cell signaling pathways involved in cell survival, cell migration and cell death reduces the mammary tumor promoting environment. PMID- 25116350 TI - Up-regulation of P21 inhibits TRAIL-mediated extrinsic apoptosis, contributing resistance to SAHA in acute myeloid leukemia cells. AB - BACKGROUND/AIM: P21, a multifunctional cell cycle-regulatory molecule, regulates apoptotic cell death. In this study we examined the effect of altered p21 expression on the sensitivity of acute myeloid leukemia cells in response to HDAC inhibitor SAHA treatment and investigated the underlying mechanism. METHODS: Stably transfected HL60 cell lines were established in RPMI-1640 with supplementation of G-418. Cell viability was measured by MTT assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-PE/7AAD assay. RESULTS: We showed HL60 cells that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated apoptosis than NB4 and U937 cells that had increased p21 level. Enforced expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated apoptosis and lethality. Finally, we found that combined treatment with SAHA and rapamycin down-regulated p21 and enhanced apoptosis in AML cells. CONCLUSION: We conclude that up-regulated p21 expression mediates resistance to SAHA via inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to predict responsiveness or resistance to SAHA-based therapy in AML patients. In addition, rapamycin may be an effective agent to override p21-mediated resistance to SAHA in AML patients. PMID- 25116352 TI - Induction of myocardial PDCD4 in coronary microembolization-related cardiac dysfunction: evidence from a large-animal study. AB - BACKGROUND/AIMS: Coronary microembolization (CME) has been linked to myocardial inflammation and apoptosis. This study aims to investigate the role of the apoptotic protein PDCD4 in the myocardium after CME in minipigs. METHODS: Seventy Bama minipigs were randomized into four groups: control, CME, CME plus PDCD4 siRNA and CME plus control siRNA. CME was induced by injecting polyethylene microspheres into the left anterior descending artery. Cardiac function was evaluated. HE and HBFP staining were used to observe the degree of infarction. Western blotting and qPCR were used to evaluate the expression of PDCD4, TNF alpha and caspase-3. The measurements were performed at 0, 3, 6, 9, 12 and 24 h after CME modeling in the CME and control groups. RESULTS: Cardiac function in the CME group was significantly decreased compared with the control group (P<0.05) and the expression of PDCD4 and TNF-alpha increased significantly (P<0.05). However, the infarct area did not differ between the CME and control groups at any time point (P>0.05). Furthermore, PDCD4-siRNA improved cardiac function and reduced PDCD4 and TNF-alpha expression compared with the CME plus control siRNA group at 9 h after modeling (P < 0.05), while the caspase-3 level was not different between the two groups. CONCLUSION: PDCD4 induction may be involved in CME-related cardiac dysfunction, and PDCD4 inhibition via siRNA may attenuate the cardiac impairment and be used as a treatment strategy for CME. PMID- 25116353 TI - Decreased MiR-200a/141 suppress cell migration and proliferation by targeting PTEN in Hirschsprung's disease. AB - BACKGROUND/AIMS: Hirschsprung's disease (HSCR) is a genetic disorder of neural crest development. In this study, we investigated whether and how miR-200a and miR-141, belonging to miR-200 family, were involved in the pathogenesis of HSCR. METHODS: Quantitative real time PCR and Western blot were used to detect the levels of miRNA, mRNAs, and proteins in colon tissues from 88 HSCR patients and 75 controls. The direct regulation of specific mRNA by miRNAs was validated by dual-luciferase reporter assay and RNA interference in cell lines. Transwell assays, CCK8 assay, and flow cytometry were inplemented to measure viability and activities of human 293T and SH-SY5Y cells, respectively. RESULTS: Aberrant suppression of miR-200a was observed in colon tissues of HSCR patients. A decreased level of miR-200a and miR-141 correlated with increased levels of PTEN mRNA and protein. The Dual-Luciferase reporter gene assay demonstrated that miR 200a and miR-141 binded directly to 3'UTR of PTEN and resulting in the inhibition of PTEN. The reductions in miR-200a and miR-141 inhibited migration and proliferation of 293T and SH-SY5Y cells through up-regulating the expression of PTEN. Moreover, knocking-down of PTEN rescued the extent of suppressed cell migration and proliferation induced by miR-200a and miR-141. CONCLUSIONS: The miR 200 family may play a crucial role in the pathogenesis of HSCR by co-regulating PTEN. PMID- 25116351 TI - Kruppel -like factor 8 is a stress-responsive transcription factor that regulates expression of HuR. AB - BACKGROUND/AIMS: HuR is an RNA-binding protein that regulates the post transcriptional life of thousands of cellular mRNAs and promotes cell survival. HuR is expressed as two mRNA transcripts that are differentially regulated by cell stress. The goal of this study is to define factors that promote transcription of the longer alternate form. METHODS: Effects of transcription factors on HuR expression were determined by inhibition or overexpression of these factors followed by competitive RT-PCR, gel mobility shift, and chromatin immunoprecipitation. Transcription factor expression patterns were identified through competitive RT-PCR and Western analysis. Stress responses were assayed in thapsigargin-treated proximal tubule cells and in ischemic rat kidney. RESULTS: A previously described NF-kappaB site and a newly identified Sp/KLF factor binding site were shown to be important for transcription of the long HuR mRNA. KLF8, but not Sp1, was shown to bind this site and increase HuR mRNA levels. Cellular stress in cultured or native proximal tubule cells resulted in a rapid decrease of KLF8 levels that paralleled those of the long HuR mRNA variant. CONCLUSIONS: These results demonstrate that KLF8 can participate in regulating expression of alternate forms of HuR mRNA along with NF-kappaB and other factors, depending on cellular contexts. PMID- 25116354 TI - Sex hormones regulate hepatic fetuin expression in male and female rats. AB - BACKGROUND: To date, there are limited studies on the sex-specific relationship between fetuins (Ft-A and Ft-B) and metabolic diseases. Our recent proteomic study has shown that fetuins may play sex-dependent roles in obesity and diabetes. In the present study, we investigated the expression of hepatic fetuins with respect to the effects of sex hormones both in vivo and in vitro. METHODS & RESULTS: A sex hormone-treated rat model was established in order to study the effects of sex hormones on hepatic fetuin expression. Animal experiments revealed that 17beta-estradiol (E2)- and dihydrotestosterone (DHT)-treated rats showed opposite effects in terms of body weight gain in both genders. Interestingly, Ft A and Ft-B were sex-dependently expressed in the livers of rats, responding to different regulatory modes of sex hormone receptors (ERalpha, ERbeta, and AR). To validate in vivo data, rat normal liver cells were treated with E2 or DHT at different concentrations, and similar expression patterns as those in the animal based experiments were confirmed. We found that these changes were mediated via sex hormone receptors using antagonist experiments. CONCLUSION: The results of the present study indicate that sex hormones induce gender-dimorphic expression of hepatic fetuins directly via sex hormone receptors. To the best of our knowledge, this is the first approach to address the effects of sex hormones on hepatic fetuin expression. PMID- 25116355 TI - OPN polymorphism is associated with the susceptibility to cervical spondylotic myelopathy and its outcome after anterior cervical corpectomy and fusion. AB - BACKGROUND: Osteopontin (OPN) is reportedly involved in bone desorption, formation and ectopic calcification. We sought to investigate the role of OPN gene polymorphism in the susceptibility to Cervical spondylotic myelopathy (CSM) and in predicting the outcome anterior cervical corpectomy and fusion (ACF). METHODS: A total of 187 patients diagnosed with CSM and 233 sex and age matched healthy controls were enrolled in this study. All CSM patients received ACF and were followed up for 24 months. The polymorphisms of OPN gene at 3 loci, namely, 156 G>GG, -443 C>T and -66T>G were determined. RESULTS: The -66T>G genotype was significantly different between CSM patients and controls. Compared to the -66TT carriers, the -66GG genotype carriers had a higher risk for developing CSM (adjusted Odd Ratio=2.58, adjusted P=0.001). In contrast, the genotype distributions of the -156G/GG and -443C/T loci were not significantly different between the CSM and control groups. OPN gene polymorphism did not determine the pre-operative severity of CSM patients, but the -66T>G genotype was significantly associated with the clinical outcome of CSM after ACF treatment. The -66T>G did not affect the serum OPN level, but affect the local expressions of OPN and a serious of key inflammatory factors in the intervertebral disc samples. CONCLUSION: Our study shows the OPN -66T>G genetic polymorphism contributes to patients' susceptibility to CSM and could be indicative of the outcome of ACF surgery. PMID- 25116356 TI - Dysregulation of the glutamine transporter Slc38a3 (SNAT3) and ammoniagenic enzymes in obese, glucose-intolerant mice. AB - BACKGROUND/AIMS: Uric acid nephrolithiasis is prevalent among patients with type 2 diabetes and metabolic syndrome; it is correlated with an acidic urine and lower urinary ammonium excretion and is likely associated with insulin resistance. Insulin stimulates ammoniagenesis in renal cell lines via increased phosphate-dependent glutaminase (PDG) activity and glutamine metabolism. Ammonium excretion into the proximal tubule is mediated at least in part by the Na(+)/H(+) exchanger NHE3 and in the collecting duct involving the Rhesus protein RhCG. Here we tested, whether obesity and insulin resistance in a diet-induced mouse model could contribute to deranged ammonium excretion. METHODS: Obesity was induced by diet in mice and the impact on key molecules of proximal tubular ammoniagenesis and urinary acid excretion tested. RESULTS: Diet-induced obesity was confirmed by pathological intraperitoneal glucose tolerance tests (IPGTT). Three groups of mice were compared: control mice; obese, glucose-intolerant with abnormal IPGTT (O-GI); or moderate weight with normal IPGTT (Non-Responders, NR). Basal urinary ammonium excretion did not differ among groups. However, acid loading increased urinary ammonium excretion in all groups, but to a lesser extent in the O-GI group. SNAT3 mRNA expression was enhanced in both obese groups. PDG expression was elevated only in acid-loaded O-GI mice, whereas PEPCK was enhanced in both O GI and NR groups given NH4CI. NHE activity in the brush border membrane of the proximal tubule was strongly reduced in the O-GI group whereas RhCG expression was similar. CONCLUSION: In sum, obesity and glucose intolerance impairs renal ammonium excretion in response to NH4CI feeding most likely through reduced NHE activity. The stimulation of SNAT3 and ammoniagenic enzyme expression may be compensatory but futile. PMID- 25116357 TI - GLP-2 suppresses LPS-induced inflammation in macrophages by inhibiting ERK phosphorylation and NF-kappaB activation. AB - BACKGROUND/AIMS: GLP-2 has been shown to exert anti-inflammatory effects, but the underlying molecular mechanisms remained undefined. As macrophages are important in the development and maintenance of inflammation, we investigated whether exogenous GLP-2 modulates the expression of pro-inflammatory proteins in LPS stimulated murine peritoneal macrophages. METHODS: Macrophages were pretreated with various concentrations of GLP-2 for 1 h and then stimulated with LPS. The effects on pro-inflammatory enzymes (iNOS and COX-2), and pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) were analysed by Western blotting, ELISA and qRT-PCR. We also examined whether NF-kappaB or MAPK signaling was involved in the effects of GLP-2. RESULTS: In macrophages, GLP-2 blunted the effect of LPS on protein and mRNA expression levels of iNOS, COX-2, TNF-alpha, IL-1beta and IL-6. Pre-incubation of macrophages with GLP-2 also blunted LPS-induced IkappaB-alpha degradation, IkappaB-alpha phosphorylation and NF-kappaB translocation. In the presence of GLP-2, the effect of LPS treatment on ERK phosphorylation was also profoundly blunted. GLP-2 did, however, not significantly modify the effects of LPS on p38 and JNK activities. CONCLUSIONS: These findings demonstrate that in LPS primed macrophages, GLP-2 reduced pro-inflammatory enzymes and cytokine production via mechanisms involving the suppression of NF-kappaB activity and ERK phosphorylation. PMID- 25116358 TI - Resveratrol suppresses oxidised low-density lipoprotein-induced macrophage apoptosis through inhibition of intracellular reactive oxygen species generation, LOX-1, and the p38 MAPK pathway. AB - BACKGROUND/AIM: Resveratrol (RSV) may have therapeutic potential for various diseases. Here we investigated the effect of RSV on oxidised low-density lipoprotein- (ox-LDL) induced apoptosis in RAW264.7 macrophages. METHODS: Apoptosis of macrophages following incubation with ox-LDL (with or without RSV pre-treatment) was detected by flow cytometry. Western blotting was used to assess the protein expression of Bax, Bcl-2, and caspase-3 as well as ox-LDL receptor 1 (LOX-1) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Reactive oxygen species (ROS) generation was evaluated by 2', 7' dichlorofluorescein diacetate, and JC-1 probe was used to determine the mitochondrial transmembrane potential of cells. RESULTS: Ox-LDL significantly reduced viability and increased the rate of apoptosis (P < 0.05) in RAW264.7 cells. However, pre-treatment with RSV resulted in a remarkable decrease in this apoptotic effect. Moreover, ox-LDL caused the up-regulation of Bax and the down regulation of Bcl-2, as well as the activation of caspase-3. Expression of LOX-1, phosphorylation of p38 MAPK, and intracellular ROS production also increased after ox-LDL stimulation. Strikingly, these effects were abolished by pre treatment of cells with RSV. CONCLUSION: RSV suppresses ox-LDL-induced macrophage apoptosis. These beneficial effects might be exerted through inhibition of ROS generation, LOX-1, and the p38 MAPK signalling pathway. PMID- 25116359 TI - Key residues responsible for enhancement of catalytic efficiency of Thermomyces lanuginosus lipase Lip revealed by complementary protein engineering strategy. AB - The variant Lip-T (S88T/A99N/V116D) of lipase Lip from Thermomyces lanuginosus has been proved to be a potential biocatalyst for kinetic resolution of 2 carboxyethyl-3-cyano-5-methylhexanoic acid ethyl ester (CNDE) to produce valuable chiral intermediate of Pregabalin. In this study, random, site-directed and site saturation mutagenesis were performed to further enhance the activity of Lip-T, and the key residues responsible for catalytic efficiency were revealed. A mutant S63L/D232A with improved activity toward CNDE was obtained after screening of approximately 2500 clones from random-mutant libraries. Site-directed mutagenesis at site 63 and 232 demonstrated that the single-point mutants S63L and D232A showed opposite effect on activity. S63L exhibited a significant improvement on activity, whereas D232A exerted a slight inhibitory effect. Then a mutant S63M with a 4.5-fold higher catalytic efficiency than Lip-T was obtained by site saturation mutagenesis. Structural changes resulting from the mutations were analyzed and the mechanisms responsible for the enhanced activity were discussed. Moreover, the engineered lipase catalyzed enantioselective hydrolysis of CNDE at a very high substrate loading (765 g/l). As only 5% (w/v) resting cells were used, the bioprocess is much more cost-effective than Pfizer's process using 8% (w/v) commercially available lipase Lipolase((r)). These results provide not only new insights into lipase structure-function relationships but also a novel robust biocatalyst for the production of Pregabalin. PMID- 25116360 TI - An electrochemical genosensor for Salmonella typhi on gold nanoparticles mercaptosilane modified screen printed electrode. AB - In this work, we fabricated a system of integrated self-assembled layer of organosilane 3-mercaptopropyltrimethoxy silane (MPTS) on the screen printed electrode (SPE) and electrochemically deposited gold nanoparticle for Salmonella typhi detection employing Vi gene as a molecular marker. Thiolated DNA probe was immobilized on a gold nanoparticle (AuNP) modified SPE for DNA hybridization assay using methylene blue as redox (electroactive) hybridization indicator, and signal was monitored by differential pulse voltammetry (DPV) method. The modified SPE was characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and atomic force microscopy (AFM) method. The DNA biosensor showed excellent performances with high sensitivity and good selectivity. The current response was linear with the target sequence concentrations ranging from 1.0 * 10(-11) to 0.5 * 10(-8)M and the detection limit was found to be 50 (+/- 2.1)pM. The DNA biosensor showed good discrimination ability to the one-base, two base and three-base mismatched sequences. The fabricated genosensor could also be regenerated easily and reused for three to four times for further hybridization studies. PMID- 25116361 TI - In situ near infrared spectroscopy monitoring of cyprosin production by recombinant Saccharomyces cerevisiae strains. AB - Near infrared (NIR) spectroscopy was used to in situ monitoring the cultivation of two recombinant Saccharomyces cerevisiae strains producing heterologous cyprosin B. NIR spectroscopy is a fast and non-destructive technique, that by being based on overtones and combinations of molecular vibrations requires chemometrics tools, such as partial least squares (PLS) regression models, to extract quantitative information concerning the variables of interest from the spectral data. In the present work, good PLS calibration models based on specific regions of the NIR spectral data were built for estimating the critical variables of the cyprosin production process: biomass concentration, cyprosin activity, cyprosin specific activity, the carbon sources glucose and galactose concentration and the by-products acetic acid and ethanol concentration. The PLS models developed are valid for both recombinant S. cerevisiae strains, presenting distinct cyprosin production capacities, and therefore can be used, not only for the real-time control of both processes, but also in optimization protocols. The PLS model for biomass yielded a R(2)=0.98 and a RMSEP=0.46 g dcw l(-1), representing an error of 4% for a calibration range between 0.44 and 13.75 g dcw l(-1). A R(2)=0.94 and a RMSEP=167 Um l(-1) were obtained for the cyprosin activity, corresponding to an error of 6.7% of the experimental data range (0 2509 Um l(-1)), whereas a R(2)=0.93 and RMSEP=672 U mg(-1) were obtained for the cyprosin specific activity, corresponding to an error of 7% of the experimental data range (0-11,690 Um g(-1)). For the carbon sources glucose and galactose, a R(2)=0.96 and a RMSECV of 1.26 and 0.55 g l(-1), respectively, were obtained, showing high predictive capabilities within the range of 0-20 g l(-1). For the metabolites resulting from the cell growth, the PLS model for acetate was characterized by a R(2)=0.92 and a RMSEP=0.06 g l (-1), which corresponds to a 6.1% error within the range of 0.41-1.23 g l(-1); for the ethanol, a high accuracy PLS model with a R(2)=0.97 and a RMSEP=1.08 g l(-1) was obtained, representing an error of 9% within the range of 0.18-21.76 g l(-1). The present study shows that it is possible the in situ monitoring and prediction of the critical variables of the recombinant cyprosin B production process by NIR spectroscopy, which can be applied in process control in real-time and in optimization protocols. From the above, NIR spectroscopy appears as a valuable analytical tool for online monitoring of cultivation processes, in a fast, accurate and reproducible operation mode. PMID- 25116362 TI - Targeted genome correction by a single adenoviral vector simultaneously carrying an inducible zinc finger nuclease and a donor template. AB - Zinc finger nuclease (ZFN) technology, which can be used to induce targeted genome correction in the presence of a DNA donor template, is becoming an attractive strategy for treating monogenic diseases. This strategy requires efficient delivery of ZFN and donor template into cells, ideally, in a single viral vector to achieve efficient genome editing and to avoid unwanted mutagenesis. In this study, we successfully produced a single adenoviral (Ad) vector with high titer that carried a ZFN expression cassette and a donor template simultaneously. We then demonstrated that this single Ad system could mediate efficient site-specific genome correction in vitro and ex vivo. The gene correction efficiency of the single Ad was significantly higher than that of the double Ad system. This novel vector will be a promising ZFN and donor delivery system for treatment of monogenic diseases. PMID- 25116365 TI - Depositional characteristics of atmospheric polybrominated diphenyl ethers on tree barks. AB - OBJECTIVES: This study was conducted to determine the depositional characteristics of several tree barks, including Ginkgo (Ginkgo biloba), Pine (Pinus densiflora), Platanus (Platanus), and Metasequoia (Metasequoia glyptostroboides). These were used as passive air sampler (PAS) of atmospheric polybrominated diphenyl ethers (PBDEs). METHODS: Tree barks were sampled from the same site. PBDEs were analyzed by highresolution gas chromatography/high resolution mass spectrometer, and the lipid content was measured using the gravimetric method by n-hexane extraction. RESULTS: Gingko contained the highest lipid content (7.82 mg/g dry), whereas pine (4.85 mg/g dry), Platanus (3.61 mg/g dry), and Metasequoia (0.97 mg/g dry) had relatively lower content. The highest total PBDEs concentration was observed in Metasequoia (83,159.0 pg/g dry), followed by Ginkgo (53,538.4 pg/g dry), Pine (20,266.4 pg/g dry), and Platanus (12,572.0 pg/g dry). There were poor correlations between lipid content and total PBDE concentrations in tree barks (R(2)=0.1011, p =0.682). Among the PBDE congeners, BDE 206, 207 and 209 were highly brominated PBDEs that are sorbed to particulates in ambient air, which accounted for 90.5% (84.3-95.6%) of the concentration and were therefore identified as the main PBDE congener. The concentrations of particulate PBDEs deposited on tree barks were dependent on morphological characteristics such as surface area or roughness of barks. CONCLUSIONS: Therefore, when using the tree barks as the PAS of the atmospheric PBDEs, samples belonging to same tree species should be collected to reduce errors and to obtain reliable data. PMID- 25116363 TI - Voluntary pressing and releasing actions induce different senses of time: evidence from event-related brain responses. AB - The timing intervals initiated by voluntary pressing actions are subjectively compressed compared with those initiated by voluntary releasing actions. Event related potentials (ERPs) were employed in the present study to uncover the temporal mechanisms underlying this temporal illusion. The results revealed that the mean amplitude of the P1 component over the frontal-central recording sites, but not the P2 component, was larger in the voluntary pressing condition than in the voluntary releasing condition at the time perception stage. In the fronto central region, increases in oscillatory activities of delta-theta frequency range (1-7 Hz) were found in the voluntary pressing condition, which corresponded with the emergence of the P1 peak. In addition, the P1 amplitude was negatively related to the corresponding reported time length at the single-trial level. These results are discussed in terms of the functional role of the response locked P1 in the time perception stage. PMID- 25116364 TI - NUCKS1, a novel Tat coactivator, plays a crucial role in HIV-1 replication by increasing Tat-mediated viral transcription on the HIV-1 LTR promoter. AB - BACKGROUND: Human immunodeficiency virus-1 (HIV-1) Tat protein plays an essential role in HIV gene transcription from the HIV-1 long terminal repeat (LTR) and replication. Transcriptional activity of Tat is modulated by several host factors, but the mechanism responsible for Tat regulation by host factors is not understood fully. RESULTS: Using a yeast two-hybrid screening system, we identified Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) as a novel Tat-interacting partner. Here, we report its function as a positive regulator of Tat. In a coimmunoprecipitation assay, HIV-1 Tat interacted sufficiently with both endogenous and ectopically expressed NUCKS1. In a reporter assay, ectopic expression of NUCKS1 significantly increased Tat-mediated transcription of the HIV-1 LTR, whereas knockdown of NUCKS1 by small interfering RNA diminished Tat-mediated transcription of the HIV-1 LTR. We also investigated which mechanism contributes to NUCKS1-mediated Tat activation. In a chromatin immunoprecipitation assay (ChIP), knockdown of NUCKS1 interrupted the accumulation of Tat in the transactivation-responsive (TAR) region on the LTR, which then led to suppression of viral replication. However, NUCKS1 expression did not increase Tat nuclear localization and interaction with Cyclin T1. Interestingly, the NUCKS1 expression level was lower in latently HIV-1-infected cells than in uninfected parent cells. Besides, expression level of NUCKS1 was markedly induced, which then facilitated HIV-1 reactivation in latently infected cells. CONCLUSION: Taken together, our data demonstrate clearly that NUCKS1 is a novel Tat coactivator that is required for Tat-mediated HIV-1 transcription and replication, and that it may contribute to HIV-1 reactivation in latently HIV-1 infected cells. PMID- 25116367 TI - Spatial analysis of PM10 and cardiovascular mortality in the Seoul metropolitan area. AB - OBJECTIVES: Numerous studies have revealed the adverse health effects of acute and chronic exposure to particulate matter less than 10 MUm in aerodynamic diameter (PM10). The aim of the present study was to examine the spatial distribution of PM10 concentrations and cardiovascular mortality and to investigate the spatial correlation between PM10 and cardiovascular mortality using spatial scan statistic (SaTScan) and a regression model. METHODS: From 2008 to 2010, the spatial distribution of PM10 in the Seoul metropolitan area was examined via kriging. In addition, a group of cardiovascular mortality cases was analyzed using SaTScan-based cluster exploration. Geographically weighted regression (GWR) was applied to investigate the correlation between PM10 concentrations and cardiovascular mortality. RESULTS: An examination of the regional distribution of the cardiovascular mortality was higher in provincial districts (gu) belonging to Incheon and the northern part of Gyeonggido than in other regions. In a comparison of PM10 concentrations and mortality cluster (MC) regions, all those belonging to MC 1 and MC 2 were found to belong to particulate matter (PM) 1 and PM 2 with high concentrations of air pollutants. In addition, the GWR showed that PM10 has a statistically significant relation to cardiovascular mortality. CONCLUSIONS: To investigate the relation between air pollution and health impact, spatial analyses can be utilized based on kriging, cluster exploration, and GWR for a more systematic and quantitative analysis. It has been proven that cardiovascular mortality is spatially related to the concentration of PM10. PMID- 25116366 TI - Skin corrosion and irritation test of sunscreen nanoparticles using reconstructed 3D human skin model. AB - OBJECTIVES: Effects of nanoparticles including zinc oxide nanoparticles, titanium oxide nanoparticles, and their mixtures on skin corrosion and irritation were investigated by using in vitro 3D human skin models (KeraSkin ((TM)) ) and the results were compared to those of an in vivo animal test. METHODS: Skin models were incubated with nanoparticles for a definite time period and cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide method. Skin corrosion and irritation were identified by the decreased viability based on the pre-determined threshold. RESULTS: Cell viability after exposure to nanomaterial was not decreased to the pre-determined threshold level, which was 15% after 60 minutes exposure in corrosion test and 50% after 45 minutes exposure in the irritation test. IL-1alpha release and histopathological findings support the results of cell viability test. In vivo test using rabbits also showed non corrosive and non-irritant results. CONCLUSIONS: The findings provide the evidence that zinc oxide nanoparticles, titanium oxide nanoparticles and their mixture are 'non corrosive' and 'non-irritant' to the human skin by a globally harmonized classification system. In vivo test using animals can be replaced by an alternative in vitro test. PMID- 25116371 TI - Summary health statistics for the u.s. Population: national health interview survey, 2011. AB - Objectives-This report presents both age-adjusted and unadjusted health statistics from the 2011 National Health Interview Survey (NHIS) for the civilian noninstitutionalized population of the United States. Estimates are disaggregated by sex, age, race, Hispanic origin, education, family income, poverty status, health insurance coverage (where appropriate), place of residence, and region of residence. The topics covered are respondent-assessed health status, limitations in activities, special education or early intervention services, injury and poisoning episodes, health care access and utilization, and health insurance coverage. Data Source-NHIS is a household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics. In 2011, household interviews were completed for 101,875 persons living in 39,509 households, reflecting a household response rate of 82.0%. Selected Highlights Nearly 7 in 10 persons were in excellent or very good health in 2011. About 40 million persons (13%) were limited in their usual activities due to one or more chronic health conditions. About 5 million persons (2%) required the help of another person with activities of daily living, and about 10 million persons (4%) required the help of another person with instrumental activities of daily living. About 7% of children received special education or early intervention services. Among persons under age 65, about 45 million (17%) did not have any health insurance coverage. The most common reason for lacking health insurance was cost, followed by a change in employment. PMID- 25116370 TI - Marine biotechnologies and synthetic biology, new issues for a fair and equitable profit-sharing commercial use. AB - The sea will be a source of economic development in the next years. Today the research works in marine biotechnologies supply new products and processes. The introduction in the laboratories of a new technology, synthesis biology, is going to increase the possibilities of creation of new products. Exploitation of product stemming from marine biodiversity has to be made with regard to various rights among which industrial property law, maritime law and the Convention on BioDiversity. All participants involved in the promotion of research in marine biotechnology must address the fair and equitable sharing of any commercial exploitation. Carrying out work involving synthetic biology has increased the number of unanswered questions about how operators should manage in order to avoid any threat of being sued for infringements of IP rights or for alleged bio piracy. This paper, by no means exhaustive in the field, analyzes some of the issues raised on the modification to the landscape in marine biotechnology by the advent of synthetic biology. Such issues indicate how important the collaboration between researchers, industrialists, lawyers is for allowing proper use of marine biotech. PMID- 25116369 TI - Older adults recently started on psychotropic medication: where are the symptoms? AB - OBJECTIVE: The objective of this study is to understand the characteristics of older adults on newly prescribed psychotropic medication with minimal psychiatric symptoms. METHODS: Naturalistic cohort study of non-institutionalized older adults in Pennsylvania participating in the Pharmaceutical Assistance Contract for the Elderly. Persons newly prescribed antidepressant or anxiolytic monotherapy or combination therapy were contacted for clinical assessment by a telephone-based behavioral health service. The initial assessment included standardized mental health screening instruments and scales including the Blessed Orientation-Memory-Concentration test, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Medical Outcomes Survey (SF-12). In addition, patients were asked for their understanding of the prescription indication. RESULTS: Of the 254 participants who met minimal symptom criteria (Patient Health Questionnaire-9 < 5 and Generalized Anxiety Disorder-7 < 5), women comprised slightly more of the anxiolytic compared with antidepressant monotherapy group (88.9% vs. 76.7%, p = 0.04). The most common self-reported reason for prescription of an antidepressant or anxiolytic was depression or anxiety, respectively, despite near-absence of these symptoms on clinical assessment. Comparing monotherapy to combination therapy groups, those with combination therapy were more likely to report a history of depression (12.6% vs. 1.8%, p < 0.001) and also report depression as the reason for the prescription (40.2% vs. 21.0%, p < 0.01). CONCLUSIONS: In this sample of older adults on new psychotropic medication with minimal psychiatric symptoms, there are few patient characteristics that distinguish those on antidepressant versus anxiolytic monotherapy or those on monotherapy versus combination therapy. While quality of care in late-life mental health has focused on improving detection and treatment, there should be further attention to low-symptom patients potentially receiving inappropriate pharmacotherapy. PMID- 25116372 TI - Treatment outcome of Chinese children with anaplastic large cell lymphoma by using a modified B-NHL-BFM-90 protocol. AB - Pediatric anaplastic large cell lymphoma (ALCL) has rarely been reported in Chinese pediatric patients. This study evaluated the clinical characteristics and treatment outcome of Chinese pediatric patients with ALCL. Between October 2002 and October 2012, 39 untreated pediatric patients with ALCL were enrolled at a single institution. The patients were stratified into three groups (R1, R2, and R3) based on the stage of the disease, clinical risk factors, and chemotherapeutic response, and received different intensive chemotherapy regimens based on a modified B-NHL-BFM-90 protocol. Of the 39 patients, 22 were boys, and 17 were girls, with a median age at diagnosis of 10 years (range 2-16 years), 91.2% were anaplastic lymphoma kinase (ALK)-positive. The patient groups R1, R2, and R3 accounted for 12.8%, 30.4%, and 56.4% of the total, respectively. 87.2% of patients were stage III/IV. At a median follow-up period of 52 months (range 15 136 months), seven patients relapsed and three patients died of their disease. The 5-year event-free survival for all patients was 81.4% +/- 6.4%, with 100%, 83.3% +/- 10% and 75.3% +/- 9.8% for groups R1, R2, and R3, respectively. The overall survival for all patients was 92.2% +/- 4.3%. Our study demonstrates that a risk-stratified treatment with a modified B-NHL-BFM-90 protocol is efficacious for Chinese children with ALCL. PMID- 25116375 TI - AgNb7O18: an ergodic relaxor ferroelectric. AB - AgNb7O18 is a relaxor ferroelectric with a Burns temperature of ~490 K and an incipient transition to the nonergodic state. The short-range structure is shown by convergent-beam electron diffraction to have the polar space group Im2m, but refinements against powder X-ray diffraction find the long-range structure to have the centrosymmetric space group Immm. Relaxor behavior in AgNb7O18 appears to originate from the partial occupation of large interstices by Ag(+) cations. Both cations and oxygen anions are displaced away from zones where NbO6 octahedra are edge-sharing. PMID- 25116373 TI - Endothelial amine oxidase AOC3 transiently contributes to adaptive immune responses in the airways. AB - Amine oxidase, copper containing 3 (AOC3, also known as vascular adhesion protein 1 (VAP-1)) is an endothelial adhesion molecule that contributes to the extravasation of neutrophils, macrophages, and lymphocytes to sites of inflammation. However, the role of AOC3/VAP-1 in allergic responses remains unknown. Here, we studied eosinophil and CD4+ T-cell recruitment to the airways using AOC3/VAP-1-deficient mice. In an OVA-triggered asthma model, AOC3/VAP-1 slightly contributed to the accumulation of leukocytes in lungs in an age dependent manner. We then established a new model to kinetically measure recruitment of OVA-specific CD4+ T cells to different airway immune compartments during the priming and effector phases of an adaptive immune response. The results showed that in the absence of AOC3/VAP-1, recruitment of antigen-specific CD4+ T cells to draining bronchial lymph nodes is reduced by 89% on day 3 after tracheal allergen exposure, but this difference was not observed on day 6. The dispersal of effector cells to lung and tracheal mucosa is AOC3/VAP-1 independent. Thus, in allergic airway reactions, AOC3/VAP-1 transiently contributes to the antigen-specific, CD4+ T-cell traffic to secondary lymphatic tissues, but not to airway mucosa or lung parenchyma. Our results suggest a largely redundant function for AOC3/VAP-1 in allergic inflammatory responses of the airways. PMID- 25116376 TI - Assisted reproduction for postmenopausal women. AB - With increasing longevity, an ageing population and advances in assisted reproductive technologies (ART), a greater number of women are deciding to have a child and become a mother in their later years. With this social and demographic change, an important social and ethical debate has emerged over whether single and/or married postmenopausal women should have access to ARTs. The aim of this paper is to address this question and review critically the arguments that have been advanced to support or oppose the use of ART by older women. The arguments presented consider the consequences for the individual, the family and wider society. They cover the potential physical and emotional harm to the older woman, the possible impact on the welfare and wellbeing of the future child, and the impact on the norms, values, customs and traditions of society. After reviewing the evidence, and weighing the opposing arguments, this paper concludes that there is no moral justification for a restriction on the use of ART by postmenopausal women. Allowing access to ART for postmenopausal women is an extension of reproductive autonomy and procreative rights in an age where the promotion of agency, autonomy, individual choice and human rights is paramount. PMID- 25116378 TI - Homologies and homeotic transformation of the theropod 'semilunate' carpal. AB - The homology of the 'semilunate' carpal, an important structure linking non-avian and avian dinosaurs, has been controversial. Here we describe the morphology of some theropod wrists, demonstrating that the 'semilunate' carpal is not formed by the same carpal elements in all theropods possessing this feature and that the involvement of the lateralmost distal carpal in forming the 'semilunate' carpal of birds is an inheritance from their non-avian theropod ancestors. Optimization of relevant morphological features indicates that these features evolved in an incremental way and the 'semilunate' structure underwent a lateral shift in position during theropod evolution, possibly as a result of selection for foldable wings in birds and their close theropod relatives. We propose that homeotic transformation was involved in the evolution of the 'semilunate' carpal. In combination with developmental data on avian wing digits, this suggests that homeosis played a significant role in theropod hand evolution in general. PMID- 25116379 TI - Oxygen etching of thick MoS2 films. AB - Oxygen annealing of thick MoS2 films results in randomly oriented and controllable triangular etched shapes, forming pits with uniform etching angles. These etching morphologies differ across the sample based on the defect sites situated on the basal plane surface, forming numerous features in different bulk sample thicknesses. PMID- 25116377 TI - Programmable nanoscaffolds that control ligand display to a G-protein-coupled receptor in membranes to allow dissection of multivalent effects. AB - A programmable ligand display system can be used to dissect the multivalent effects of ligand binding to a membrane receptor. An antagonist of the A2A adenosine receptor, a G-protein-coupled receptor that is a drug target for neurodegenerative conditions, was displayed in 35 different multivalent configurations, and binding to A2A was determined. A theoretical model based on statistical mechanics was developed to interpret the binding data, suggesting the importance of receptor dimers. Using this model, extended multivalent arrangements of ligands were constructed with progressive improvements in binding to A2A. The results highlight the ability to use a highly controllable multivalent approach to determine optimal ligand valency and spacing that can be subsequently optimized for binding to a membrane receptor. Models explaining the multivalent binding data are also presented. PMID- 25116381 TI - An improved method for including upper size range plasmids in metamobilomes. AB - Two recently developed isolation methods have shown promise when recovering pure community plasmid DNA (metamobilomes/plasmidomes), which is useful in conducting culture-independent investigations into plasmid ecology. However, both methods employ multiple displacement amplification (MDA) to ensure suitable quantities of plasmid DNA for high-throughput sequencing. This study demonstrates that MDA greatly favors smaller circular DNA elements (<10 Kbp), which, in turn, leads to stark underrepresentation of upper size range plasmids (>10 Kbp). Throughout the study, we used two model plasmids, a 4.4 Kbp cloning vector (pBR322), and a 56 Kbp conjugative plasmid (pKJK10), to represent lower- and upper plasmid size ranges, respectively. Subjecting a mixture of these plasmids to the overall isolation protocol revealed a 34-fold over-amplification of pBR322 after MDA. To address this bias, we propose the addition of an electroelution step that separates different plasmid size ranges prior to MDA in order to reduce size dependent competition during incubation. Subsequent analyses of metamobilome data from wastewater spiked with the model plasmids showed in silica recovery of pKJK10 to be very poor with the established method and a 1,300-fold overrepresentation of pBR322. Conversely, complete recovery of pKJK10 was enabled with the new modified protocol although considerable care must be taken during electroelution to minimize cross-contamination between samples. For further validation, non-spiked wastewater metamobilomes were mapped to more than 2,500 known plasmid genomes. This displayed an overall recovery of plasmids well into the upper size range (median size: 30 kilobases) with the modified protocol. Analysis of de novo assembled metamobilome data also suggested distinctly better recovery of larger plasmids, as gene functions associated with these plasmids, such as conjugation, was exclusively encoded in the data output generated through the modified protocol. Thus, with the suggested modification, access to a large uncharacterized pool of accessory elements that reside on medium-to-large plasmids has been improved. PMID- 25116382 TI - Heat-killed probiotic bacteria differentially regulate colonic epithelial cell production of human beta-defensin-2: dependence on inflammatory cytokines. AB - The inducible antimicrobial peptide human beta-defensin-2 (hBD-2) stimulated by pro-inflammatory cytokines and bacterial products is essential to antipathogen responses of gut epithelial cells. Commensal and probiotic bacteria can augment such mucosal defences. Probiotic use in the treatment of inflammatory bowel disease, however, may have adverse effects, boosting inflammatory responses. The aim of this investigation was to determine the effect of selected probiotic strains on hBD-2 production by epithelial cells induced by pathologically relevant pro-inflammatory cytokines and the role of cytokine modulators in controlling hBD-2. Caco-2 colonic intestinal epithelial cells were pre-incubated with heat-killed probiotics, i.e. Lactobacillus casei strain Shirota (LcS) or Lactobacillus fermentum strain MS15 (LF), followed by stimulation of hBD-2 by interleukin (IL)-1beta and tumour necrosis factor alpha (TNF-alpha) in the absence or presence of exogenous IL-10 or anti-IL-10 neutralising antibody. Cytokines and hBD-2 mRNA and protein were analysed by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. LcS augmented IL 1beta-induced hBD-2, whereas LF enhanced TNF-alpha- and suppressed IL-1beta induced hBD-2. LF enhanced TNF-alpha-induced TNF-alpha and suppressed IL-10, whereas augmented IL-1beta-induced IL-10. LcS upregulated IL-1beta-induced TNF alpha mRNA and suppressed IL-10. Endogenous IL-10 differentially regulated hBD-2; neutralisation of IL-10 augmented TNF-alpha- and suppressed IL-1beta-induced hBD 2. Exogenous IL-10, however, suppressed both TNF-alpha- and IL-1beta-induced hBD 2; LcS partially rescued suppression in TNF-alpha- and IL-1beta-stimulation, whereas LF further suppressed IL-1beta-induced hBD-2. It can be concluded that probiotic strains differentially regulate hBD-2 mRNA expression and protein secretion, modulation being dictated by inflammatory stimulus and resulting cytokine environment. PMID- 25116383 TI - Testing the proclaimed affordances of online support groups in a nationally representative sample of adults seeking mental health assistance. AB - In this study, explanations for why people turn to the Internet for social support are tested using a nationally representative sample of adults who sought mental health support through a traditional treatment outlet, an in-person support group, or an online support group. Results indicate that the more adults report having social stigma concerns, the more likely they are to seek support online instead of help from an in-person support group or traditional treatment. Likewise, as the reported number of logistical barriers to mental health treatment increases, a corresponding increase occurs in the odds of adults seeking online support instead of traditional treatment. These findings as well as estimates of demographic variation in the use of online support are discussed. PMID- 25116380 TI - Acetylation-dependent regulation of essential iPS-inducing factors: a regulatory crossroad for pluripotency and tumorigenesis. AB - Induced pluripotent stem (iPS) cells can be generated from somatic cells by coexpression of four transcription factors: Sox2, Oct4, Klf4, and c-Myc. However, the low efficiency in generating iPS cells and the tendency of tumorigenesis hinder the therapeutic applications for iPS cells in treatment of human diseases. To this end, it remains largely unknown how the iPS process is subjected to regulation by upstream signaling pathway(s). Here, we report that Akt regulates the iPS process by modulating posttranslational modifications of these iPS factors in both direct and indirect manners. Specifically, Akt directly phosphorylates Oct4 to modulate the Oct4/Sox2 heterodimer formation. Furthermore, Akt either facilitates the p300-mediated acetylation of Oct4, Sox2, and Klf4, or stabilizes Klf4 by inactivating GSK3, thus indirectly modulating stemness. As tumorigenesis shares possible common features and mechanisms with iPS, our study suggests that Akt inhibition might serve as a cancer therapeutic approach to target cancer stem cells. PMID- 25116384 TI - Vitamin D insufficiency over 5 years is associated with increased fracture risk an observational cohort study of elderly women. AB - This study of elderly Swedish women investigated the association between chronic vitamin D insufficiency and osteoporotic fractures occurring between ages 80-90. The incidence and risk of hip and major osteoporotic fractures was significantly higher in elderly women with low vitamin D levels maintained over 5 years. INTRODUCTION: Vitamin D insufficiency among the elderly is common; however, relatively little is known about the effects of long-term hypovitaminosis D on fracture. We investigated sequential assessment of serum 25(OH)D at age 75 and 80 to determine if continuously low 25(OH)D levels are associated with increased 10 year fracture incidence. METHODS: One thousand forty-four Swedish women from the population-based OPRA cohort, all 75 years old, attended at baseline (BL); 715 attended at 5 years. S-25(OH)D was available in 987 and 640, respectively and categorized as: <50 (Low), 50-75 (Intermediate), and >75 nmol/L (High). Incident fracture data was collected with maximum follow-up to 90 years of age. RESULTS: Hip fracture incidence between age 80-85 was higher in women who had low 25(OH)D at both baseline and 5 years (22.2 % (Low) vs. 6.6 % (High); p = 0.003). Between age 80-90, hip fracture incidence was more than double that of women in the high category (27.9 vs. 12.3 %; p = 0.006). Within 5-years, 50 % of women in the continuously low group compared to 34 % in the continuously high 25(OH)D group had an osteoporotic fracture (p = 0.004) while 10-year incidence was higher compared to the intermediate (p = 0.020) but not the high category (p = 0.053). The 10-year relative risk of hip fracture was almost three times higher and osteoporotic fracture risk almost doubled for women in the lowest 25(OH)D category compared to the high category (HR 2.7 and 1.7; p = 0.003 and 0.023, respectively). CONCLUSION: In these elderly women, 25(OH)D insufficiency over 5 years was associated with increased 10-year risk of hip and major osteoporotic fractures. PMID- 25116385 TI - Vitamin D: is evidence of absence, absence of evidence? PMID- 25116386 TI - Response to letter to editor. PMID- 25116388 TI - Construction of four low-dimensional NIR-luminescence-tunable Yb(III) complexes. AB - Four low-dimensional ytterbium(iii)-organic compounds through hydrothermal reactions of quinoline-2,3-dicarboxylic acid (2,3-H2qldc) and oxalic acid (H2ox) with Yb2O3, namely, [Yb(2,3-qldc)(ox)1/2(H2O)3.(H2O)4]n (1), [Yb(2,3 qldc)(ox)1/2(H2O)2.(H2O)2]n (2), [Yb(2,3-Hqldc)(ox)(H2O)2.(H2O)]n (3) and [Yb(2,3 Hqldc)(ox)(H2O).(H2O)2]n (4), were first synthesized and characterized by elemental analysis (EA), infrared spectroscopy (IR), thermogravimetric analysis (TG), and single-crystal X-ray diffraction. When the reactant ratio of 2,3-H2qldc : H2ox : Yb2O3 is 2 : 1 : 1, 1-D chain-like complex 1 with three coordinated water molecules around the Yb(iii) ion was obtained in mixed solvents of H2O and CH3OH (v : v = 10 : 1) at 70 degrees C, and with the increase of temperature to 100 degrees C, the same reactants gave 2-D 6(3) topological layer-like complex 2 with two coordinated water molecules in the coordination sphere of the Yb(iii) ion. However, when the reactant ratio was changed to 1 : 1 : 1, two 2-D 6(3) topological layer-like complexes 3 (70 degrees C) and 4 (100 degrees C) were obtained at different temperatures, in which the coordination water molecules in 3 and 4 are two and one, respectively. Obviously, these results reveal that the reaction temperature and reactant ratios play critical roles in the structural direction of these low-dimensional compounds. Interestingly, with the gradual loss of coordination water molecules to the Yb(iii) ion, the near infrared (NIR) emission of four Yb(iii)-based compounds 1-4 can be gradually strengthened with increasing order of 1 < 3 < 2 < 4, indicating that these ytterbium(iii) complexes have tunable near infrared luminescence. PMID- 25116387 TI - Using RNA-seq and targeted nucleases to identify mechanisms of drug resistance in acute myeloid leukemia. AB - The evolution from microarrays to transcriptome deep-sequencing (RNA-seq) and from RNA interference to gene knockouts using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and Transcription Activator-Like Effector Nucleases (TALENs) has provided a new experimental partnership for identifying and quantifying the effects of gene changes on drug resistance. Here we describe the results from deep-sequencing of RNA derived from two cytarabine (Ara-C) resistance acute myeloid leukemia (AML) cell lines, and present CRISPR and TALEN based methods for accomplishing complete gene knockout (KO) in AML cells. We found protein modifying loss-of-function mutations in Dck in both Ara-C resistant cell lines. CRISPR and TALEN-based KO of Dck dramatically increased the IC50 of Ara-C and introduction of a DCK overexpression vector into Dck KO clones resulted in a significant increase in Ara-C sensitivity. This effort demonstrates the power of using transcriptome analysis and CRISPR/TALEN-based KOs to identify and verify genes associated with drug resistance. PMID- 25116389 TI - Sequences outside that of residues 93-102 of 3A protein can contribute to the ability of foot-and-mouth disease virus (FMDV) to replicate in bovine-derived cells. AB - Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals. During 2010 and 2011, there was an epidemic of the Mya-98 lineage of the Southeast Asia (SEA) topotype in East Asia, including China. Changes in the FMDV 3A protein have been previously reported to be associated with the inability of FMDV to grow in bovine cells and cause disease in cattle. In this paper, we report the generation of a full-length infectious cDNA clone of FMDV O/SEA/Mya-98 strain O/GZSB/2011 for the first time along with two genetically modified viruses with deletion at positions 93-102 and 133-143 in 3A based on the established infectious clone. All the recombinant viruses grew well and displayed growth properties and plaque phenotypes similar to those of the parental virus in baby hamster kidney (BHK-21) cells, porcine kidney (PK-15) cells, and primary fetal porcine kidney (FPK) cells. While the recombinant viruses rvGZSB and rvSBDelta133-143 exhibited similar growth properties and plaque phenotypes with the parental virus in primary fetal bovine kidney (FBK) cells, the recombinant virus rvSBDelta93-102, containing deletion at positions 93 102 in 3A, grew at a slower rate and had a smaller plaque size phenotype in FBK cells than that of the parental virus. Therefore, the results suggest that the deletion at positions 93-102 of 3A protein does not affect FMDV replication efficiency in BHK-21, PK-15 and FPK cells, but affects virus replication efficiency in FBK cells, although, cannot alone account for the inability to replicate in bovine cells. PMID- 25116390 TI - Activation of PI3K/Akt pathway limits JNK-mediated apoptosis during EV71 infection. AB - Apoptosis is frequently induced to inhibit virus replication during infection of Enterovirus 71 (EV71). On the contrary, anti-apoptotic pathway, such as PI3K/Akt pathway, is simultaneously exploited by EV71 to accomplish the viral life cycle. The relationship by which EV71-induced apoptosis and PI3K/Akt signaling pathway remains to be elucidated. In this study, we demonstrated that EV71 infection altered Bax conformation and triggered its redistribution from the cytosol to mitochondria in RD cells. Subsequently, cytochrome c was released from mitochondria to cytosol. We also found that c-Jun NH2-terminal kinase (JNK) was activated during EV71 infection. The JNK specific inhibitor significantly inhibited Bax activation and cytochrome c release, suggesting that EV71-induced apoptosis was involved into a JNK-dependent manner. Meanwhile, EV71-induced Akt phosphorylation involved a PI3K-dependent mechanism. Inhibition of the PI3K/Akt pathway enhanced JNK phosphorylation and the JNK-mediated apoptosis upon EV71 infection. Moreover, PI3K/Akt pathway phosphorylated apoptosis signal-regulating kinase 1 (ASK1) and negatively regulated the ASK1 activity. Knockdown of ASK1 significantly decreased JNK phosphorylation, which implied that ASK1 phosphorylation by Akt inhibited ASK1-mediated JNK activation. Collectively, these data reveal that activation of the PI3K/Akt pathway limits JNK-mediated apoptosis by phosphorylating and inactivating ASK1 during EV71 infection. PMID- 25116391 TI - The SARS Coronavirus 3a protein binds calcium in its cytoplasmic domain. AB - The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a positive stranded RNA virus with ~30kb genome. Among all open reading frames (orfs) of this virus, the orf3a is the largest, and encodes a protein of 274 amino acids, named as 3a protein. Sequence analysis suggests that the orf3a aligned to one calcium pump present in Plasmodium falciparum and the enzyme glutamine synthetase found in Leptospira interrogans. This sequence similarity was found to be limited only to amino acid residues 209-264 which form the cytoplasmic domain of the orf3a. Furthermore, this region was predicted to be involved in the calcium binding. Owing to this hypothesis, we were driven to establish its calcium binding property in vitro. Here, we expressed and purified the cytoplasmic domain of the 3a protein, called Cyto3a, as a recombinant His-tagged protein in the E. coli. The calcium binding nature was established by performing various staining methods such as ruthenium red and stains-all. (45)Ca overlay method was also done to further support the data. Since the 3a protein forms ion channels, we were interested to see any conformational changes occurring in the Cyot3a upon calcium binding, using fluorescence spectroscopy and circular dichroism. These studies clearly indicate a significant change in the conformation of the Cyto3a protein after binding with calcium. Our results strongly suggest that the cytoplasmic domain of the 3a protein of SARS-CoV binds calcium in vitro, causing a change in protein conformation. PMID- 25116392 TI - Porcine epidemic diarrhea virus infects and replicates in porcine alveolar macrophages. AB - Porcine epidemic diarrhea virus (PEDV) is a causative agent of porcine epidemic diarrhea; consequently, the small intestine was believed to be its only target organ. In this study, we found that PEDV infected not only the small intestines, but also the respiratory tract. Infection and replication of PEDV in the respiratory tract from naturally PEDV-infected piglets were examined by reverse transcription polymerase chain reaction, immunohistochemistry, and virus re isolation. Our observations were confirmed by experimental inoculation, and we found that PEDV infection in the respiratory tract was specifically associated with alveolar macrophages in the lung. Vero cell-adapted PEDV was able to replicate in both primary alveolar macrophages and continuous porcine alveolar macrophage cells. Sequencing analysis of the spike (S) glycoprotein revealed that mutations in S might be a potential determinant of auxiliary targets for PEDV. The discovery that PEDV infects and replicates in alveolar macrophages provides new insights into its pathogenesis. PMID- 25116396 TI - Nursing and the new biology: towards a realist, anti-reductionist approach to nursing knowledge. AB - As a system of knowledge, nursing has utilized a range of subjects and reconstituted them to reflect the thinking and practice of health care. Often drawn to a holistic model, nursing finds it difficult to resist the reductionist tendencies in biological and medical thinking. In this paper I will propose a relational approach to knowledge that is able to address this issue. The paper argues that biology is not characterized by one stable theory but is often a contentious topic and employs philosophically diverse models in its scientific research. Biology need not be seen as a reductionist science, but reductionism is nonetheless an important current within biological thinking. These reductionist currents can undermine nursing knowledge in four main ways. Firstly, that the conclusions drawn from reductionism go far beyond their data based on an approach that prioritizes biological explanations and eliminates others. Secondly, that the methods employed by biologists are sometimes weak, and the limitations are insufficiently acknowledged. Thirdly, that the assumptions that drive the research agenda are problematic, and finally that uncritical application of these ideas can be potentially disastrous for nursing practice. These issues are explored through an examination of the problems reductionism poses for the issue of gender, mental health, and altruism. I then propose an approach based on critical realism that adopts an anti-reductionist philosophy that utilizes the conceptual tools of emergence and a relational ontology. PMID- 25116395 TI - Solution and high-pressure NMR studies of the structure, dynamics, and stability of the cross-reactive allergenic cod parvalbumin Gad m 1. AB - Beta-parvalbumins from different fish species have been identified as the main elicitors of IgE-mediated reactions in fish-allergic individuals. Here, we report for the first time the NMR determination of the structure and dynamics of the major Atlantic cod (Gadus morhua) allergen Gad m 1 and compare them with other known parvalbumins. Although the Gad m 1 structure and accessibility of putative IgE epitopes are similar to parvalbumins in mackerel and carp, the charge distribution at the putative epitopes is different. The determination of the Gad m 1 structure contributes to a better understanding of cross-reactivity among fish parvalbumins. In addition, the high-pressure NMR and temperature variation experiments revealed the important contribution of the AB motif and other regions to the protein folding. This structural information could assist the future identification of hot spots for targeted mutations to develop hypoallergenic Ca(2+) -free forms for potential use in immunotherapy. PMID- 25116393 TI - Overexpression of Gremlin-1 in patients with Loeys-Dietz syndrome: implications on pathophysiology and early disease detection. AB - BACKGROUNDS: The Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder caused by mutations in the transforming growth factor beta (TGF-beta) receptors TGFBR1 or TGFBR2. Most patients with LDS develop severe aortic aneurysms resulting in early need of surgical intervention. In order to gain further insight into the pathophysiology of the disorder, we investigated circulating outgrowth endothelial cells (OEC) from the peripheral blood of LDS patients from a cohort of 23 patients including 6 patients with novel TGF-beta receptor mutations. METHODS AND RESULTS: We performed gene expression profiling of OECs using microarray analysis followed by quantitative PCR for verification of gene expression. Compared to OECs of age- and sex-matched healthy controls, OECs isolated from three LDS patients displayed altered expression of several genes belonging to the TGF-beta pathway, especially those affecting bone morphogenic protein (BMP) signalling including BMP2, BMP4 and BMPR1A. Gene expression of BMP antagonist Gremlin-1 (GREM1) showed the most prominent up regulation. This increase was confirmed at the protein level by immunoblotting of LDS-OECs. In immunohistochemistry, abundant Gremlin-1 protein expression could be verified in endothelial cells as well as smooth muscle cells within the arterial media. Furthermore, Gremlin-1 plasma levels of LDS patients were significantly elevated compared to healthy control subjects. CONCLUSIONS: These findings open new avenues in the understanding of the pathogenesis of Loeys-Dietz syndrome and the development of new diagnostic serological methods for early disease detection. PMID- 25116394 TI - Hypoxia preconditioned mesenchymal stem cells prevent cardiac fibroblast activation and collagen production via leptin. AB - AIMS: Activation of cardiac fibroblasts into myofibroblasts constitutes a key step in cardiac remodeling after myocardial infarction (MI), due to interstitial fibrosis. Mesenchymal stem cells (MSCs) have been shown to improve post-MI remodeling an effect that is enhanced by hypoxia preconditioning (HPC). Leptin has been shown to promote cardiac fibrosis. The expression of leptin is significantly increased in MSCs after HPC but it is unknown whether leptin contributes to MSC therapy or the fibrosis process. The objective of this study was to determine whether leptin secreted from MSCs modulates cardiac fibrosis. METHODS: Cardiac fibroblast (CF) activation was induced by hypoxia (0.5% O2). The effects of MSCs on fibroblast activation were analyzed by co-culturing MSCs with CFs, and detecting the expression of alpha-SMA, SM22alpha, and collagen IalphaI in CFs by western blot, immunofluorescence and Sirius red staining. In vivo MSCs antifibrotic effects on left ventricular remodeling were investigated using an acute MI model involving permanent ligation of the left anterior descending coronary artery. RESULTS: Co-cultured MSCs decreased fibroblast activation and HPC enhanced the effects. Leptin deficit MSCs from Ob/Ob mice did not decrease fibroblast activation. Consistent with this, H-MSCs significantly inhibited cardiac fibrosis after MI and mediated decreased expression of TGF-beta/Smad2 and MRTF-A in CFs. These effects were again absent in leptin-deficient MSCs. CONCLUSION: Our data demonstrate that activation of cardiac fibroblast was inhibited by MSCs in a manner that was leptin-dependent. The mechanism may involve blocking TGF-beta/Smad2 and MRTF-A signal pathways. PMID- 25116397 TI - A potential biomarker in sports-related concussion: brain functional connectivity alteration of the default-mode network measured with longitudinal resting-state fMRI over thirty days. AB - Current diagnosis and monitoring of sports-related concussion rely on clinical signs and symptoms, and balance, vestibular, and neuropsychological examinations. Conventional brain imaging often does not reveal abnormalities. We sought to assess if the longitudinal change of functional and structural connectivity of the default-mode network (DMN) can serve as a potential biomarker. Eight concussed Division I collegiate football student-athletes in season (one participated twice) and 11 control subjects participated in this study. ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing) was administered over the course of recovery. High-resolution three dimensional T1-weighted, T2* weighted diffusion-tensor images and resting-state functional magnetic resonance imaging (rs-fMRI) scans were collected from each subject within 24 h, 7+/-1 d and 30+/-1 d after concussion. Both network based and whole-brain based functional correlation analyses on DMN were performed. ImPACT findings demonstrated significant cognitive impairment across multiple categories and a significant increase of symptom severity on Day 1 following a concussion but full recovery by 6.0+/-2.4 d. While the structural connectivity within DMN and gross anatomy appeared unchanged, a significantly reduced functional connectivity within DMN from Day 1 to Day 7 was found in the concussed group in this small pilot study. This reduction was seen in eight of our nine concussion cases. Compared with the control group, there appears a general trend of increased DMN functional connectivity on Day 1, a significant drop on Day 7, and partial recovery on Day 30. The results of this pilot study suggest that the functional connectivity of DMN measured with longitudinal rs-fMRI can serve as a potential biomarker to monitor the dynamically changing brain function after sports-related concussion, even in patients who have shown clinical improvement. PMID- 25116398 TI - Schistosoma mansoni antigen detects Schistosoma mekongi infection. AB - Northern Cambodia and Southern Laos are highly endemic for Schistosoma mekongi. However, there is currently no immunological assay available that is specific for this form of schistosomiasis. We have validated Schistosoma mansoni antigens to detect S. mekongi-directed antibodies in human sera collected from a highly S. mekongi endemic region in Laos. On two consecutive days stool samples of 234 individuals were analyzed by Kato-Katz for presence of S. mekongi eggs and the results were correlated with serology. A sensitivity of 94.5% was calculated for a combination of ELISA and indirect fluorescence assay (IFA) as compared to the detection of S. mekongi eggs in stool samples as gold standard. The results demonstrate that S. mansoni antigens can be used for the diagnosis of S. mekongi infections. PMID- 25116399 TI - A systematic review on the quality of life benefits after percutaneous coronary intervention in the elderly. AB - AIMS: Percutaneous coronary intervention (PCI) is being increasingly performed on elderly patients with acceptable peri-procedural outcomes and long-term survival. We aim to systematically review the health-related quality of life (HRQOL) following PCI in the elderly which is an important measure of procedural success. METHODS: A systematic review of clinical studies before September 2012 was performed to identify HRQOL in the elderly after PCI. Strict inclusion and exclusion criteria were applied. Quality appraisal of each study was also performed using pre-defined criteria. HRQOL results were synthesised through a narrative review with full tabulation of results of all included studies. RESULTS: Elderly patients have significant improvements in cardiovascular well being. Early HRQOL appears improved from baseline, but recovery in physical health may be slower than in younger patients. HRQOL is comparable to an age matched general population and younger patients undergoing PCI. Conservative management is not able to offer the same HRQOL benefits. Coronary artery bypass graft surgery may be superior to PCI in the very elderly. Significant heterogeneity and bias exists. Lack of appropriate data precluded meta-analysis. CONCLUSION: HRQOL after PCI in the elderly can improve for at least 1 year across a broad range of health domains, and is comparable to an age-matched general population and younger patients undergoing PCI. Given a limited number of articles and patients included, more prospective studies are needed to better identify the benefits for elderly patients. PMID- 25116400 TI - Summary health statistics for u.s. Adults: national health interview survey, 2011. AB - Objectives-This report presents health statistics from the 2011 National Health Interview Survey (NHIS) for the civilian noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, education, family income, poverty status, health insurance coverage, marital status, and place and region of residence. Estimates (frequencies and percentages) are presented for selected chronic conditions and mental health characteristics, functional limitations, health status, health behaviors, health care access and utilization, and human immunodeficiency virus testing. Percentages and percent distributions are presented in both age-adjusted and unadjusted versions. Data Source-NHIS is a household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics. In 2011, data were collected on 33,014 adults in the Sample Adult questionnaire. The conditional response rate was 81.6%, and the final response rate was 66.3%. The health information for adults in this report was obtained from one randomly selected adult per family. In very rare instances where the sample adult was not able to respond for himself or herself, a proxy was used. Highlights-In 2011, 61% of adults aged 18 and over had excellent or very good health. Eleven percent of adults had been told by a doctor or other health professional that they had heart disease, 24% had been told on two or more visits that they had hypertension, 9% had been told that they had diabetes, and 22% had been told that they had some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Nineteen percent of adults were current smokers, and 21% were former smokers. Based on estimates of body mass index, 34% of adults were overweight and 28% were obese. PMID- 25116401 TI - Nilotinib in combination with carboplatin and paclitaxel is a candidate for ovarian cancer treatment. AB - PURPOSE: Nilotinib is a selective tyrosine kinase inhibitor of c-Kit, Abl and platelet-derived growth factor receptor-alpha/beta. To evaluate nilotinib's potential use as a treatment of human ovarian cancer, we tested nilotinib's preclinical activity in ovarian cancer cell lines with different tyrosine kinase expression patterns. METHODS: The effects of nilotinib on ovarian cancer cell growth were studied alone and in combination with carboplatin and paclitaxel. Proapoptotic and antimigratory effects were examined using TUNEL and migration assays. RESULTS: Nilotinib alone and in combination with carboplatin and paclitaxel significantly inhibited cell growth in PDGFR-alpha-positive ovarian cancer cell lines. The combination of nilotinib with carboplatin and paclitaxel showed synergistic effects on cell proliferation. Nilotinib treatment led to the inhibition of cell migration alone and in combination with carboplatin and paclitaxel. Apoptosis induction occurred in response to nilotinib that increased in combination with carboplatin. CONCLUSIONS: Nilotinib may be a feasible targeted therapy option for the treatment of ovarian cancer. PMID- 25116402 TI - Unrelated CD3/CD19-depleted peripheral stem cell transplantation for Hurler syndrome. AB - For patients with mucopolysaccharidosis type IH (MPS1-H; Hurler syndrome), early allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice. One boy and one girl aged 20.5 and 22 months, respectively, with MPS1-H received a conditioning regimen consisting of thiotepa, fludarabine, treosulfan, and ATG. Grafts were peripheral blood stem cells from unrelated donors (10/12 and 11/11 matched), that were manipulated by CD3/CD19 depletion and contained 20.3 and 28.2 * 10(6) CD34+ cells/kg body weight, respectively. Both patients achieved stable hematopoietic engraftment and stable donor chimerism. Neither acute or chronic graft-versus-host disease (GVHD) nor other severe transplant-related complications occurred. At a follow-up of 48 and 37 months, both patients are alive and well with normal levels of alpha-L-iduronidase and have made major neurodevelopmental progress. Treosulfan-based conditioning offers the advantage of reduced toxicity; the use of unrelated CD3/CD19-depleted peripheral stem cell grafts allows transfusion of high CD34+ cell numbers together with a "tailored" number of CD3+ cells as well as engraftment facilitating cells in order to achieve rapid hematopoietic engraftment while reducing the risk of graft rejection and GVHD. This regimen might be an additional option when unrelated donor HSCT is considered for a patient with MPS1-H. PMID- 25116403 TI - Assisted reproductive technology--IVF treatment in Ireland: a study of couples with successful outcomes. AB - This article describes the experiences of twelve Irish couples who had successful IVF treatment in Ireland. Irish Medical guidelines specify that IVF may only be used when no other treatment is likely to be effective. This article is based on data drawn from a longitudinal research study by Cotter (2009) which tells the stories of 34 couples who sought fertility treatment. Initially, the women assumed that they would become pregnant when they stopped using contraception. As a couple, it was the 'right time' for them to have a child--they were ready, socially and financially. For several months they were patient, hoping it would happen naturally. With envy and some despair they watched as their friends had babies. Infertility came as a shock to most of them. They were reluctant to talk about it to anyone, and over time their anxieties were accompanied by feelings of regret, stigma and social exclusion. They finally sought medical treatment. The latter involved a series of diagnostic treatments, which eventually culminated in IVF which offered them a final chance of having a 'child of their own'. While IVF can be clinically assessed in terms of cycle success rates, their stories showed treatment as a series of discoveries, as an extensive range of diagnostic tests and procedures helped to reveal to them where their problems might lie. They described their treatments as a series of sequential 'hurdles' that they had to overcome, which further strengthened their resolve to try IVF. Much more knowledgeable at that stage, they embraced IVF as a final challenge with single minded dedication while drawing on all their psychological and biological resources to promote a successful outcome. Of the 34 couples who took part in the study, twelve got pregnant. Unfortunately, two children died shortly after birth but eighteen babies survived (see Table I). The findings suggest that health policy should raise awareness of infertility, and advise women to become aware of it--just as in the past, when health policy addressed contraception. Increased public knowledge would reduce the stigma attached to the inability to have a baby. In the Irish case, infertility diagnosis should be reviewed with a view to giving eligible couples earlier access to IVF. PMID- 25116405 TI - Synthesis, structures, and solution dynamics of tetrasubstituted nine-atom germanium deltahedral clusters. AB - Reported are the rational synthesis, structures, and solution dynamics of three tetrasubstituted and neutral Ge9-based deltahedral clusters [Ge9R3R'](0), where R = Si(SiMe3)3 and R' = Et (1), Sn(n)Bu3 (2), or Tl (3). The first step of the synthesis is a reaction of an acetonitrile suspension of the intermetallic precursor compound K4Ge9 with {Si(SiMe3)3}Cl which produces the trisubstituted monoanions [Ge9{Si(SiMe3)3}](-). A benzene suspension of the latter is then reacted with Sn(n)Bu3Cl or TlCp to produce 2 and 3, respectively, while the same acetonitrile solution is reacted with EtBr in order to produce 1. All three structures can be viewed as tricapped trigonal prisms of Ge9 with the three "hypersilyl" substituents, Si(SiMe3)3, exo-bonded to the capping atoms. The fourth substituent in 1, the ethyl group, is exo-bonded to one of the six available Ge atoms with the Ge-C bond positioned radially to the Ge9 core. In the case of 2, on the other hand, the tin fragment is found above one of the triangular bases of the prism interacting with one or more Ge atoms in three crystallographically different molecules in the structure. Lastly, the Tl atom in the structure of 3 is found capping a pseudosquare face between two hypersilyl substituents. NMR spectroscopy indicates that all three compounds are dynamic at room temperature. Variable-temperature studies suggest that the process in 1 and 2 is intramolecular while the process in 3 involves dissociation of the Tl(+) ion from the molecule followed by association at the same or another equivalent pseudosquare face of the molecule. Thus, the latter compound may be considered to a large extent to be ionic as it is made of a thallium cation and a trisubstituted cluster anion. PMID- 25116406 TI - Cd(II)-MOF: adsorption, separation, and guest-dependent luminescence for monohalobenzenes. AB - A series of isostructural 2-fold interpenetrating 2D Cd(II)-MOFs, namely G?CdL2(OTs)2 (G = THF (1), PhF (2), PhCl (3), PhBr (4), PhI (5), L = 1,2-bis[(3 (pyridin-4-yl)phenoxy]ethane, and OTs(-) = p-toluenesulfonate anion), have been successfully synthesized from the flexible ethylene glycol ether-bridging ligand L and Cd(OTs)2 in solution. The CdL2(OTs)2 framework contains squarelike nonpolar channels, and the encapsulated guest molecules can be removed by heating (150 degrees C) to generate a guest-free host framework which is able to reversibly adsorb monohalobenzenes PhX (X = F, Cl, Br, I) in the liquid phase under ambient conditions without loss of framework integrity. Furthermore, it can effectively separate these monohalobenzenes and exhibits a clear affinity for monohalobenzenes according to the following order: PhI > PhBr > PhCl > PhF. In addition, PhX?CdL2(OTs)2 exhibits guest-dependent luminescence properties. PMID- 25116404 TI - IL-33 attenuates the development of experimental autoimmune uveitis. AB - Interleukin-33 (IL-33) is associated with several important immune-mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here, we investigated the function of IL-33 in the development of experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (ST2) were expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL-33 increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naive mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-gamma+ and IL-17(+) CD4+ T cells and reduced IFN-gamma and IL-17 production but with increased frequency of IL-5(+) and IL-4(+) CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization toward an alternatively activated macrophage phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis. PMID- 25116408 TI - Symptomatic excyclotorsion following inferior transposition of both medial rectus muscles in patients with bilateral trochlear nerve palsy. AB - PURPOSE: To report the development of a large degree of excyclotorsion following inferior transposition of the medial rectus muscles in 5 patients with bilateral acquired trochlear nerve palsies that had previously undergone bilateral modified Harada-Ito procedures. METHODS: The medical records of 5 patients who had undergone Harada-Ito procedure for bilateral trochlear nerve palsy between 2002 and 2010 and medial rectus muscle infraplacement surgery between 2004 and 2012 were retrospectively reviewed. RESULTS: All 5 patients underwent a Fells-modified Harada-Ito procedure. All remained symptomatic due to a V pattern (eso- or exodeviation). Bilateral inferior transposition of the medial rectus muscles of either half or full tendon width was performed to alleviate this residual diplopia. The vertical transposition resulted in a symptomatic large degree of excyclotorsion (mean of 20 degrees ), which required reversal of the procedure. CONCLUSIONS: After inferior transposition of both medial rectus muscles in patients with bilateral superior oblique palsy who previously had bilateral modified Harada-Ito surgery, a large excyclotorsion (>20 degrees ) can occur. This can be managed by reversing the medial rectus transposition procedure. PMID- 25116407 TI - The newt reprograms mature RPE cells into a unique multipotent state for retinal regeneration. AB - The reprogramming of retinal pigment epithelium (RPE) cells in the adult newt immediately after retinal injury is an area of active research for the study of retinal disorders and regeneration. We demonstrate here that unlike embryonic/larval retinal regeneration, adult newt RPE cells are not directly reprogrammed into retinal stem/progenitor cells; instead, they are programmed into a unique state of multipotency that is similar to the early optic vesicle (embryo) but preserves certain adult characteristics. These cells then differentiate into two populations from which the prospective-neural retina and RPE layers are formed with the correct polarity. Furthermore, our findings provide insight into the similarity between these unique multipotent cells in newts and those implicated in retinal disorders, such as proliferative vitreoretinopathy, in humans. These findings provide a foundation for biomedical approaches that aim to induce retinal self-regeneration for the treatment of RPE mediated retinal disorders. PMID- 25116409 TI - Second to fourth digit ratio: a predictor of adult testicular volume. AB - It has been suggested that second to fourth digit ratio (digit ratio) may correlate with male reproductive system function or disorders. This hypothesis is based on finding that the Hox genes control finger development and differentiation of the genital bud during embryogenesis. Thus, we investigated the association between digit ratio and adult testicular volume. A total of 172 Korean men (aged 20-69 years) hospitalized for urological surgery were prospectively enrolled. Patients with conditions known to strongly influence testicular volume were excluded. Before determining testicular volume, the lengths of the second and fourth digits of the right hand were measured by a single investigator using a digital vernier calliper. Using orchidometry, the testes were measured by an experienced urologist who had no information about the patient's digit ratio. To identify the independent predictive factors influencing testicular volume, univariate and multivariate analyses were performed using linear regression models. Age, height, serum testosterone and free testosterone level were not correlated with testicular volume. Digit ratio, along with weight, was significantly correlated with testicular volume (right testicular volume: r = -0.185, p = 0.015; left testicular volume: r = -0.193, p = 0.011; total testicular volume: r = -0.198, p = 0.009). Multivariate analysis using linear regression models showed that only digit ratio was the independent factor to predict all (right, left and total) testicular volumes (right testicular volume: beta = -0.174, p = 0.023; left testicular volume: beta = -0.181, p = 0.017; total testicular volume: beta = -0.185, p = 0.014). Our findings demonstrated that digit ratio is negatively associated with adult testicular volume. This means that men with a higher digit ratio may be more likely to have smaller testis compared to those with a lower digit ratio. PMID- 25116410 TI - A mechanistic study on SMOB-ADP1: an NADH:flavin oxidoreductase of the two component styrene monooxygenase of Acinetobacter baylyi ADP1. AB - Two styrene monooxygenase types, StyA/StyB and StyA1/StyA2B, have been described each consisting of an epoxidase and a reductase. A gene fusion which led to the chimeric reductase StyA2B and the occurrence in different phyla are major differences. Identification of SMOA/SMOB-ADP1 of Acinetobacter baylyi ADP1 may enlighten the gene fusion event since phylogenetic analysis indicated both proteins to be more related to StyA2B than to StyA/StyB. SMOB-ADP1 is classified like StyB and StyA2B as HpaC-like reductase. Substrate affinity and turnover number of the homo-dimer SMOB-ADP1 were determined for NADH (24 uM, 64 s(-1)) and FAD (4.4 uM, 56 s(-1)). SMOB-ADP1 catalysis follows a random sequential mechanism, and FAD fluorescence is quenched upon binding to SMOB-ADP1 (K d = 1.8 uM), which clearly distinguishes that reductase from StyB of Pseudomonas. In summary, this study confirmes made assumptions and provides phylogenetic and biochemical data for the differentiation of styrene monooxygenase-related flavin reductases. PMID- 25116412 TI - The surface chemistry of metal-organic frameworks. AB - Metal-organic frameworks (MOFs) have received particular attention over the last 20 years as a result of their attractive properties offering potential applications in a number of areas. Typically, these characteristics are tuned by functionalisation of the bulk of the MOF material itself. This Feature Article focuses instead on modification of MOF particles at their surfaces only, which can also offer control over the bulk properties of the material. The differing surface modification techniques available to the synthetic chemist will be discussed, with a focus on the effect of surface modification of MOFs on their fundamental properties and application in adsorption, catalysis, drug delivery and other areas. PMID- 25116411 TI - Carbon partitioning to the terpenoid biosynthetic pathway enables heterologous beta-phellandrene production in Escherichia coli cultures. AB - Escherichia coli was used as a microbial system for the heterologous synthesis of beta-phellandrene, a monoterpene of plant origin with several potential commercial applications. Expression of Lavandula angustifolia beta-phellandrene synthase (PHLS), alone or in combination with Picea abies geranyl-diphosphate synthase in E. coli, resulted in no beta-phellandrene accumulation, in sharp contrast to observations with PHLS-transformed cyanobacteria. Lack of beta phellandrene biosynthesis in E. coli was attributed to the limited endogenous carbon partitioning through the native 2-C-methylerythritol-4-phosphate (MEP) pathway. Heterologous co-expression of the mevalonic acid pathway, enhancing cellular carbon partitioning and flux toward the universal isoprenoid precursors, isopentenyl-diphosphate and dimethylallyl-diphosphate, was required to confer beta-phellandrene production. Differences in endogenous carbon flux toward the synthesis of isoprenoids between photosynthetic (Synechocystis) and non photosynthetic bacteria (E. coli) are discussed in terms of differences in the regulation of carbon partitioning through the MEP biosynthetic pathway in the two systems. PMID- 25116413 TI - Cervical cancer prevention in Malawi: a qualitative study of women's perspectives. AB - Researchers posit that cervical cancer knowledge is central to participation in prevention behaviors. However, of the many barriers to cervical cancer prevention in low- and middle-income countries, cervical cancer knowledge remains severely limited among communities at great risk for the disease. Malawi is one such country where the burden of cervical cancer is considerably high. Formative research targeting cervical cancer prevention is needed, particularly research that explores ways to deliver cervical cancer information efficiently and effectively to Malawian women. In this study, the authors aimed to garner Malawian women's understanding of cervical cancer and to shed light on preferences for health information delivery, including community health advocacy. Qualitative, in-depth interviews were conducted with 30 Malawian women and analyzed for recurring themes. In general, women had limited cervical cancer knowledge, which supported misperceptions about the disease, including factors pertaining to risk and prevention. Nonetheless, women reported that receiving cervical cancer information from trusted sources would help promote preventive behaviors. Women noted that they received most of their health information from hospital personnel, but distance was a barrier. Women also expressed interest in community health advocacy. Perspectives from Malawian women may be vital toward informing efforts to increase cervical cancer knowledge and prevention. PMID- 25116414 TI - Reassessing the improbability of a muscular crinoid stem. AB - Muscular articulations in modern stalked crinoids are only present in the arms. Although it has been suggested that certain coiled-stemmed fossil taxa may have been functionally adapted to utilize muscles, evidence supporting this interpretation is lacking. Here, we use cathodoluminescence and SEM to reveal the skeletal microstructure of the enigmatic coiled-stemmed taxon Ammonicrinus (Flexibilia). Based on the well-established link between skeletal microstructure and the nature of infilling soft tissues in modern echinoderms, we reconstructed the palaeoanatomy of the Middle Devonian ammonicrinids. We show that their median columnals with elongated lateral columnal enclosure extensions (LCEE) have stereom microstructure unexpectedly resembling that in the crinoid muscular arm plates. In particular, large ligamentary facets, that are present on each side of a transverse ridge, are mainly comprised of fine galleried stereom that is indicative of the mutable collagenous tissues. In contrast, fine labyrinthic stereom, commonly associated with muscles, is situated in the periphery on each side of the surface of elongated LCEE. Our findings thus strongly suggest that the muscles may have also been present in the stem of ammonicrinids. These results reassess the previous hypotheses about evolution of muscles in crinoids and provide new insights into the mode of life of Ammonicrinus. PMID- 25116415 TI - A time course-dependent metastatic gene expression signature predicts outcome in human metastatic melanomas. AB - BACKGROUND: The prognosis of patients with metastatic melanomas is extremely heterogeneous. Therefore, identifying high-risk subgroups by using innovative prediction models would help to improve selection of appropriate management options. METHODS: In this study, two datasets (GSE7929 and GSE7956) of mRNA expression microarray in an animal melanoma model were normalized by frozen Robust Multi-Array Analysis and then combined by the distance-weighted discrimination method to identify time course-dependent metastasis-related gene signatures by Biometric Research Branch-ArrayTools (BRB)-ArrayTools. Then two datasets (GSE8401 and GSE19234) of clinical melanoma samples with relevant clinical and survival data were used to validate the prognosis signature. RESULTS: A novel 192-gene set that varies significantly in parallel with the increasing of metastatic potentials was identified in the animal melanoma model. Further, this gene signature was validated to correlate with poor prognosis of human metastatic melanomas but not of primary melanomas in two independent datasets. Furthermore, multivariate Cox proportional hazards regression analyses demonstrated that the prognostic value of the 192-gene set is independent of the TNM stage and has higher areas under the receiver operating characteristic curve than stage information in both validation datasets. CONCLUSION: Our findings suggest that a time course-dependent metastasis-related gene expression signature is useful in predicting survival of malignant melanomas and might be useful in informing treatment decisions for these patients. PMID- 25116417 TI - Assessment of long-term prognosis at detection of early hepatocellular carcinoma remains unsolved. PMID- 25116416 TI - Physiological and brain activity after a combined cognitive behavioral treatment plus video game therapy for emotional regulation in bulimia nervosa: a case report. AB - BACKGROUND: PlayMancer is a video game designed to increase emotional regulation and reduce general impulsive behaviors, by training to decrease arousal and improve decision-making and planning. We have previously demonstrated the usefulness of PlayMancer in reducing impulsivity and improving emotional regulation in bulimia nervosa (BN) patients. However, whether these improvements are actually translated into brain changes remains unclear. OBJECTIVE: The aim of this case study was to report on a 28-year-old Spanish woman with BN, and to examine changes in physiological variables and brain activity after a combined treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT). METHODS: Ten VGT sessions were carried out on a weekly basis. Anxiety, physiological, and impulsivity measurements were recorded. The patient was scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching task, and (2) a multi-source interference task (MSIT). RESULTS: Upon completing the treatment, a decrease in average heart rate was observed. The functional magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in reaction time along with high accuracy. The patient engaged areas typically active in healthy controls, although the cluster extension of the active areas decreased after the combined treatment. CONCLUSIONS: These results suggest a global improvement in emotional regulation and impulsivity control after the VGT therapy in BN, demonstrated by both physiological and neural changes. These promising results suggest that a combined treatment of CBT and VGT might lead to functional cerebral changes that ultimately translate into better cognitive and emotional performances. PMID- 25116418 TI - Severe methemoglobinemia due to ingestion of toxicants. AB - BACKGROUND: Toxin-induced methemoglobinemia is seen in poisoning with oxidizing agents. We report the clinical features and outcome of patients admitted with severe methemoglobinemia due to intentional ingestion of toxicants. METHODS: In this observational case series, patients admitted with toxin-induced methemoglobinemia between September 2011 and January 2014 were identified from the institutional poisoning database. Clinical profile and outcome of patients with methemoglobin concentration greater than or equal to 49% is reported. RESULTS: Of the 824 patients admitted with poisoning, 5 patients with methemoglobin concentration greater than or equal to 49% were included. The implicated compounds were nitrobenzene, benzoylphenylurea, flubendamide and Rishab(TM). One patient refused to name the compound. All patients were managed in the intensive care unit. Altered sensorium [Glasgow coma scale (GCS) < 10] was common (80%); 2 patients presented with a GCS greater than 4. All patients manifested cyanosis, low oxygen saturation and chocolate-brown-colored blood despite supplemental oxygen therapy. The median methemoglobin concentration was 64.7% (range 49.8-91.6%); 2 patients had methemoglobin concentration greater than 70%. One patient needed inotropes. Four patients required mechanical ventilation for 4-14 days. All patients were treated with methylene blue; 4 received more than one dose. Three patients also received intravenous ascorbic acid 500 mg, once daily, for 3 days. Following treatment, there was evidence of haemolysis in all patients; 2 required blood transfusion. All patients survived. CONCLUSION: Patients with severe toxin-induced methemoglobinemia present with altered sensorium and cyanosis and may require ventilatory support and inotropes. Though methemoglobin concentrations greater than 70% are considered fatal, aggressive management with methylene blue and supportive therapy can lead to survival. PMID- 25116419 TI - Features of myocardial injury in severe organophosphate poisoning. AB - BACKGROUND: In organophosphate (OP) poisoning cardiac complications may occur. However, the current body of knowledge largely consists of limited studies, and case reports are mainly on electrocardiogram (ECG) abnormalities. As definite myocardial injury is difficult to assess through ECG, we investigated the prevalence of myocardial injury through cardiac biochemical markers such as troponin I (TnI) in severe OP poisoning. METHODS: We conducted a retrospective review of 99 consecutive OP insecticide poisoning cases that were diagnosed and treated at the emergency department of the Wonju Severance Christian Hospital between March 2008 and December 2013. RESULTS: Based on Namba classification for OP poisoning, there were no patients with mild toxicity, 9 patients (9.1%) with moderate toxicity and 90 patients (90.9%) with severe toxicity. On ECG, normal sinus rhythm was most common, and ST depression and elevation were seen in 11 patients (11.1%). Elevation of TnI within 48 h was seen in 34 patients (34.3%). The median peak level and peak time of TnI were 0.305 (IQR, 0.078-2.335) ng/mL and 15 (IQR 6.9-34.4) hours, respectively. There were differences between patients with normal TnI and elevated TnI in terms of age (yrs), number of patients who were exposed to OP via the oral route, and initial Glasgow Coma Scale (GCS; 58 +/- 17 vs. 66 +/- 16, p = 0.015, 56 [87.5%] vs. 33 [97.1%], p = 0.048 and 12.0 [IQR, 8.0-15.0] vs. 9.0 [IQR, 5.8-12.0], p = 0.019). CONCLUSIONS: OP can cause direct myocardial injury during the acute early phase in severe OP poisoning. Monitoring of TnI may be needed in severe OP poisoning. PMID- 25116420 TI - Homeostatic regulation of meiotic DSB formation by ATM/ATR. AB - Ataxia-telangiectasia mutated (ATM) and RAD3-related (ATR) are widely known as being central players in the mitotic DNA damage response (DDR), mounting responses to DNA double-strand breaks (DSBs) and single-stranded DNA (ssDNA) respectively. The DDR signalling cascade couples cell cycle control to damage sensing and repair processes in order to prevent untimely cell cycle progression while damage still persists [1]. Both ATM/ATR are, however, also emerging as essential factors in the process of meiosis; a specialised cell cycle programme responsible for the formation of haploid gametes via two sequential nuclear divisions. Central to achieving accurate meiotic chromosome segregation is the introduction of numerous DSBs spread across the genome by the evolutionarily conserved enzyme, Spo11. This review seeks to explore and address how cells utilise ATM/ATR pathways to regulate Spo11-DSB formation, establish DSB homeostasis and ensure meiosis is completed unperturbed. PMID- 25116422 TI - A transnational perspective on psychosurgery: beyond Portugal and the United States. AB - The history of psychosurgery is most often recounted as a narrative wherein Portuguese and American physicians play the leading role. It is a traditional narrative in which the United States and, at times, Portugal are central in the development and spread of psychosurgery. Here we largely abandon the archetypal narrative and provide one of the first transnational accounts of psychosurgery to demonstrate the existence of a global psychosurgical community in which more than 40 countries participated, bolstered, critiqued, modified and heralded the treatment. From its inception in 1935 until its decline in the mid-1960s, psychosurgery was performed on almost all continents. Rather than being a phenomenon isolated to the United States and Portugal, it became a truly transnational movement. PMID- 25116421 TI - Helix stability of oligoglycine, oligoalanine, and oligo-beta-alanine dodecamers reflected by hydrogen-bond persistence. AB - Helices are important structural/recognition elements in proteins and peptides. Stability and conformational differences between helices composed of alpha- and beta-amino acids as scaffolds for mimicry of helix recognition has become a theme in medicinal chemistry. Furthermore, helices formed by beta-amino acids are experimentally more stable than those formed by alpha-amino acids. This is paradoxical because the larger sizes of the hydrogen-bonding rings required by the extra methylene groups should lead to entropic destabilization. In this study, molecular dynamics simulations using the second-generation force field, AMOEBA (Ponder, J.W., et al., Current status of the AMOEBA polarizable force field. J Phys Chem B, 2010. 114(8): p. 2549-64.) explored the stability and hydrogen-bonding patterns of capped oligo-beta-alanine, oligoalanine, and oligoglycine dodecamers in water. The MD simulations showed that oligo-beta alanine has strong acceptor+2 hydrogen bonds, but surprisingly did not contain a large content of 3(12) -helical structures, possibly due to the sparse distribution of the 3(12) -helical structure and other structures with acceptor+2 hydrogen bonds. On the other hand, despite its backbone flexibility, the beta alanine dodecamer had more stable and persistent <3.0 A hydrogen bonds. Its structure was dominated more by multicentered hydrogen bonds than either oligoglycine or oligoalanine helices. The 3(1) (PII) helical structure, prevalent in oligoglycine and oligoalanine, does not appear to be stable in oligo-beta alanine indicating its competition with other structures (stacking structure as indicated by MD analyses). These differences are among the factors that shape helical structural preferences and the relative stabilities of these three oligopeptides. PMID- 25116423 TI - Exome sequencing of three cases of familial exceptional longevity. AB - Exceptional longevity (EL) is a rare phenotype that can cluster in families, and co-segregation of genetic variation in these families may point to candidate genes that could contribute to extended lifespan. In this study, for the first time, we have sequenced a total of seven exomes from exceptionally long-lived siblings (probands >= 103 years and at least one sibling >= 97 years) that come from three separate families. We have focused on rare functional variants (RFVs) which have <= 1% minor allele frequency according to databases and that are likely to alter gene product function. Based on this, we have identified one candidate longevity gene carrying RFVs in all three families, APOB. Interestingly, APOB is a component of lipoprotein particles together with APOE, and variants in the genes encoding these two proteins have been previously associated with human longevity. Analysis of nonfamilial EL cases showed a trend, without reaching statistical significance, toward enrichment of APOB RFVs. We have also identified candidate longevity genes shared between two families (5-13) or within individual families (66-156 genes). Some of these genes have been previously linked to longevity in model organisms, such as PPARGC1A, NRG1, RAD52, RAD51, NCOR1, and ADCY5 genes. This work provides an initial catalog of genes that could contribute to exceptional familial longevity. PMID- 25116426 TI - Health behaviors of adults: United States, 2008-2010. AB - Objective-This report presents selected prevalence estimates for key health behaviors-alcohol use, cigarette smoking, leisure-time physical activity, body mass index, and sleep-among U.S. adults, using data from the 2008-2010 National Health Interview Survey (NHIS). NHIS is a continuous survey conducted annually by the Centers for Disease Control and Prevention's National Center for Health Statistics. Estimates are shown for several sociodemographic subgroups for both sexes combined and for men and women separately. Methods-Data representing the U.S. civilian noninstitutionalized population were collected using computer assisted personal interviews. NHIS is a general purpose in-person household survey, collecting basic health, health care utilization, and demographic information on all household members with the Family questionnaire. Health behavior questions are asked in the Sample Adult survey component. This report is based on a total of 76,669 completed interviews with sample adults aged 18 and over. Statistics shown in this report were age adjusted to the projected 2000 U.S. population. Results-About 6 in 10 (64.9%) U.S. adults were current drinkers in 2008-2010; about 1 in 5 adults (20.9%) were lifetime abstainers. About one in five adults (20.2%) were current smokers and over one-half of adults (58.6%) had never smoked cigarettes. Less than one-half of current smokers (45.8%) attempted to quit smoking in the past year. Nearly one-half (46.1%) of adults met the federal guidelines for aerobic physical activity, about one-quarter (23.0%) of adults met the federal guidelines for muscle-strengthening physical activity, and about one in five adults (19.4%) met both guidelines. About 6 in 10 adults (62.1%) were overweight or obese (BMI >= 25), with about 4 in 10 (36.1%) adults being of healthy weight (18.5 <= BMI less than 25). About 7 in 10 adults (69.7%) met the Healthy People 2020 objective for sufficient sleep. PMID- 25116424 TI - Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomyelitis. AB - Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-gamma production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naive T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS. PMID- 25116425 TI - Racial, social, and clinical determinants of hepatocellular carcinoma surveillance. AB - OBJECTIVES: Less than 1 in 5 patients receive hepatocellular carcinoma surveillance; however, most studies were performed in racially and socioeconomically homogenous populations, and few used guideline-based definitions for surveillance. The study objective was to characterize guideline consistent hepatocellular carcinoma surveillance rates and identify determinants of hepatocellular carcinoma surveillance among a racially and socioeconomically diverse cohort of cirrhotic patients. METHODS: We retrospectively characterized hepatocellular carcinoma surveillance among cirrhotic patients followed between July 2008 and July 2011 at an urban safety-net hospital. Inconsistent surveillance was defined as at least 1 screening ultrasound during the 3-year period, annual surveillance was defined as screening ultrasounds every 12 months, and biannual surveillance was defined as screening ultrasounds every 6 months. Univariate and multivariate analyses were conducted to identify predictors of surveillance. RESULTS: Of 904 cirrhotic patients, 603 (67%) underwent inconsistent surveillance. Failure to recognize cirrhosis was a significant barrier to surveillance use (P < .001). Inconsistent surveillance was associated with insurance status (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.03 1.98), multiple primary care visits per year (OR, 2.63; 95% CI, 1.86-3.71), multiple hepatology visits per year (OR, 3.75; 95% CI, 2.64-5.33), African American race (OR, 0.61; 95% CI, 0.42-0.99), nonalcoholic steatohepatitis cause (OR, 0.60; 95% CI, 0.37-0.98), and extrahepatic cancer (OR, 0.43; 95% CI, 0.24 0.77). Only 98 (13.4%) of 730 patients underwent annual surveillance, and only 13 (1.7%) of 786 had biannual surveillance. CONCLUSIONS: Only 13% of patients with cirrhosis receive annual surveillance, and less than 2% of patients receive biannual surveillance. There are racial and socioeconomic disparities, with lower rates of hepatocellular carcinoma surveillance among African Americans and underinsured patients. PMID- 25116427 TI - Safety and efficacy of warfarin plus aspirin combination therapy for giant coronary artery aneurysm secondary to Kawasaki disease: a meta-analysis. AB - OBJECTIVE: To compare the safety and efficacy of warfarin plus aspirin versus aspirin alone for the treatment of children with giant coronary artery aneurysm (CAA) secondary to Kawasaki disease (KD). METHODS: We searched the PubMed, EMBASE, Cochrane Library, CNKI, WANFAN and VIP databases. We selected case controlled trials of warfarin plus aspirin versus aspirin alone for the treatment of children with giant CAA secondary to KD. RESULTS: Six retrospective studies met our inclusion criteria. There was no significant difference between the warfarin plus aspirin and aspirin alone groups in the rate of CAA regression (OR 1.38, 95% CI 0.52-3.68, p = 0.52) or the incidence of persistent CAA (OR 2.34, 95% CI 0.16-33.50, p = 0.53), coronary artery stenosis (OR 0.55, 95% CI 0.18 1.72, p = 0.30) or thrombus formation (OR 0.50, 95% CI 0.15-1.69, p = 0.26). There was evidence that warfarin plus aspirin reduced the incidence of coronary artery occlusion (OR 0.08, 95% CI 0.02-0.29, p < 0.0001), cardiac infarction (OR 0.27, 95% CI 0.11-0.63, p = 0.003) and death (OR 0.18, 95% CI 0.04-0.88, p = 0.03). CONCLUSION: Warfarin plus aspirin therapy reduced the incidence of occlusion, cardiac infarction and death in children with giant CAA secondary to KD. PMID- 25116428 TI - Screening for bipolar disorder: confusion between case-finding and screening. PMID- 25116429 TI - Red cell glucose 6-phosphate dehydrogenase deficiency in the northern region of Turkey: is G6PD deficiency exclusively a male disease? AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis. However, this disease affects both males and females. In Turkey, the frequency of this enzyme deficiency was reported to vary, from 0.25 to 18%, by the geographical area. Its prevalence in the northern Black Sea region of Turkey is unknown. The aims of this study were to assess the prevalence of G6PD deficiency in the northern region Turkey in children and adults with hyperbilirubinemia and hemolytic anemia. This report included a total of 976 G6PD enzyme results that were analyzed between May 2005 and January 2014. G6PD deficiency was detected in 5.0% of all patients. G6PD deficiency was significantly less frequent in females (1.9%, 6/323) than in males (6.6%, 43/653). G6PD deficiency was detected in 3.7% of infants with hyperbilirubinemia, 9.2% of children, and 4.5% of adults with hemolytic anemia. In both the newborn group and the group of children, G6PD deficiency was significantly more frequent in males. In the combined group of children (groups I and II), the proportion of males was 74% and 67% in all groups (P = .0008). In conclusion, in northern region of Turkey, G6PD deficiency is an important cause of neonatal hyperbilirubinemia and hemolytic crisis in children and adults. This study suggests that most pediatricians thought that G6PD deficiency is exclusively a male disease. For this reason, some female patients may have been undiagnosed. PMID- 25116431 TI - "Suddenly, bang, one day there's commitment with a woman..." men, vasectomy and the life course. AB - Research that investigates and theorises the male reproductive life course is extremely limited, and often reduced to examining problems, such as infertility. As a consequence, what we know about men's reproductive decision making is often extrapolated from theorisation of the female reproductive life course, or simplistic assumptions about masculine identity. This article analyses interview data from 34 men talking about their vasectomy decision-making processes in order to provide a lens through which to understand men making sense of their reproductive life course. Men who had children spoke of their vasectomy as resolving their lay understandings of the 'normal' life course, men who did not want their children to speak of resisting the normal life course, and men who had experienced or considered relationship dissolution spoke of resetting the life course. PMID- 25116433 TI - Facile formation of homoleptic Au(III) trications via simultaneous oxidation and ligand delivery from [PhI(pyridine)2](2+). AB - We report the first examples of Au(III) tricationic complexes bound only by neutral monodentate ligands, which are a new class of gold reagents. Oxidative addition to the bis-pyridine Au(I) cation, [Au(4-DMAP)2](+), using a series of dicationic I(III) oxidants of the general form [PhI(L)2](2+) (L = pyridine, 4 DMAP, 4-cyanopyridine) allows ready access to homoleptic and pseudo-homoleptic Au(III) complexes [Au(4-DMAP)2(L)2](3+). The facile oxidative addition of Au(I) species additionally demonstrates the efficacy of PhI(L)2](2+) reagents as halide free oxidants for Au(I). Comparisons are made via attempts to oxidize NHC Au(I)Cl, where introduction of the chloride anion results in complex mixtures via ligand and chloride exchange, demonstrating the advantage of using the pyridine based homoleptic compounds. The new Au(III) trications show intriguing reactivity with water, yielding dinuclear oxo-bridged and rare terminal Au(III)-OH complexes. PMID- 25116430 TI - Conserved expression of the GPR151 receptor in habenular axonal projections of vertebrates. AB - The habenula is a phylogenetically conserved brain structure in the epithalamus. It is a major node in the information flow between fronto-limbic brain regions and monoaminergic brainstem nuclei, and is thus anatomically and functionally ideally positioned to regulate emotional, motivational, and cognitive behaviors. Consequently, the habenula may be critically important in the pathophysiology of psychiatric disorders such as addiction and depression. Here we investigated the expression pattern of GPR151, a G protein-coupled receptor (GPCR), whose mRNA has been identified as highly and specifically enriched in habenular neurons by in situ hybridization and translating ribosome affinity purification (TRAP). In the present immunohistochemical study we demonstrate a pronounced and highly specific expression of the GPR151 protein in the medial and lateral habenula of rodent brain. Specific expression was also seen in efferent habenular fibers projecting to the interpeduncular nucleus, the rostromedial tegmental area, the rhabdoid nucleus, the mesencephalic raphe nuclei, and the dorsal tegmental nucleus. Using confocal microscopy and quantitative colocalization analysis, we found that GPR151-expressing axons and terminals overlap with cholinergic, substance P ergic, and glutamatergic markers. Virtually identical expression patterns were observed in rat, mouse, and zebrafish brains. Our data demonstrate that GPR151 is highly conserved, specific for a subdivision of the habenular neurocircuitry, and constitutes a promising novel target for psychiatric drug development. PMID- 25116434 TI - Gadolinium oxalate derivatives with enhanced magnetocaloric effect via ionothermal synthesis. AB - Two new oxalate-bridged Gd(III) coordination polymers, namely, (choline)[Gd(C2O4)(H2O)3Cl]Cl.H2O (1) and [Gd(C2O4)(H2O)3Cl] (2), were first obtained ionothermally by using a deep eutectic solvent (DES). The magnetic studies and heat capacity measurements reveal that the two-dimensional Gd(III) based coordination polymer of 2 has the higher magnetic density and exhibits a larger cryogenic magnetocaloric effect (MCE) (DeltaS(m) = 48 J kg(-1) K(-1) for DeltaH = 7 T at 2.2 K). PMID- 25116437 TI - Foamy gland carcinoma in core needle biopsies of the prostate: clinicopathologic and immunohistochemical study of 56 cases. AB - Foamy gland carcinoma is a subtype of acinar adenocarcinoma characterized by foamy appearance, large cytoplasm, pyknotic nuclei, inconspicuous nucleoli and infiltrative pattern. In this study, we investigated the histological features and the incidence of foamy gland carcinoma. We compared foamy gland carcinoma with acinar adenocarcinoma according to age, prostate-specific antigen value, Gleason score, peripheral nerve invasion and accompanying high-grade prostatic intraepithelial neoplasia. Besides, we investigated the diagnostic value of immunohistochemical markers in foamy gland carcinoma. A total of 863 TRUS-guided prostate needle core biopsies performed at our hospital pathology clinic between January 1, 2010, and December 31, 2011, were examined, 251 of these were diagnosed acinar type adenocarcinoma. Conventional acinar type adenocarcinoma was present in 195 (78%) cases, and foamy gland carcinoma, in 56 cases (22%). We found that 11 (19%) of the 56 foamy gland carcinoma cases were pure and 45 (81%) cases were mixed with conventional acinar type adenocarcinoma. Single-core localization was present in 7 of 14 pure foamy gland carcinomas, and the number of cases with a Gleason score of 7 and above was 21 (37%). No statistically significant difference was found between foamy gland carcinoma and conventional acinar type adenocarcinoma in terms of age, Gleason score, high-grade prostatic intraepithelial neoplasia, and prostate-specific antigen values. Peripheral nerve invasion was found to be statistically significantly more common in foamy gland carcinoma compared to acinar type adenocarcinoma (P<.05). The staining percentage of immunohistochemical markers in foamy gland carcinoma was 90.1% for p63, 90.6% for 34Beta12 and 90.6% for AMACR. PMID- 25116436 TI - Artesunate abolishes germinal center B cells and inhibits autoimmune arthritis. AB - The antimalarial drug artemisinin and its derivatives exhibit potent immunosuppressive activity in several autoimmune disease models, however the mechanisms are not well-understood. This study was designed to investigate the therapeutic effects and the underlying mechanisms of the artemisinin analog artesunate using the K/BxN mouse model of rheumatoid arthritis. The well-studied disease mechanisms of K/BxN model allowed us to pinpoint the effect of artesunate on disease. Artesunate treatment prevented arthritis development in young K/BxN mice by inhibiting germinal center (GC) formation and production of autoantibodies. In adult K/BxN mice with established arthritis, artesunate diminished GC B cells in a few days. However, artesunate did not affect the follicular helper T cells (Tfh). In contrast to the spontaneous K/BxN model, artesunate treatment exerted minor influence on K/BxN serum transfer induced arthritis suggesting that artesunate has minimal effect on inflammatory responses downstream of antibody production. Finally, we showed that artesunate preferentially inhibits proliferating GC B cells. These results identify GC B cells as a target of artesunate and provide a new rationale for using artemisinin analogues to treat autoimmune diseases mediated by autoantibodies. PMID- 25116439 TI - Autonomic healing of acrylic bone cement. AB - Self-healing in orthopedic bone cement is demonstrated with a novel thermoplastic solvent-bonding approach. Low toxicity solvent-filled microcapsules, embedded in a commercial acrylic bone cement matrix, enable recovery of up to 80% of the virgin fracture toughness of the cement at room and body temperature conditions without external stimuli or human intervention. PMID- 25116435 TI - Functional tooth restoration by next-generation bio-hybrid implant as a bio hybrid artificial organ replacement therapy. AB - Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy. PMID- 25116440 TI - Experimental and theoretical study of the influence of the state of dispersion of graphene on the percolation threshold of conductive graphene/polystyrene nanocomposites. AB - The effect of the dispersed state of graphene is studied as a factor influencing the electrical percolation threshold of graphene/polystyrene nanocomposites. We find the percolation threshold of our nanocomposites, prepared with graphene dispersions with different thermodynamic stabilities, degrees of exfoliation, and size polydispersities, to range from 2 to 4.5 wt %. Connectedness percolation theory is applied to calculate percolation thresholds of the corresponding nanocomposites, based on the premise that size polydispersity of graphene platelets in the corresponding solutions must have a strong influence on it. Theory and experimental results agree qualitatively. PMID- 25116442 TI - Investigation of acyl migration in mono- and dicaffeoylquinic acids under aqueous basic, aqueous acidic, and dry roasting conditions. AB - Acyl migration in chlorogenic acids describes the process of migration of cinnamoyl moieties from one quinic acid alcohol group to another, thus interconverting chlorogenic acid regioisomers. It therefore constitutes a special case of transesterification reaction. Acyl migration constitutes an important reaction pathway in both coffee roasting and brewing, altering the structure of chlorogenic acid initially present in the green coffee bean. In this contribution we describe detailed and comprehensive mechanistic studies comparing inter- and intramolecular acyl migration involving the seven most common chlorogenic acids in coffee. We employe aqueous acidic and basic conditions mimicking the brewing of coffee along with dry roasting conditions. We show that under aqueous basic conditions intramolecular acyl migration is fully reversible with basic hydrolysis competing with acyl migration. 3-Caffeoylquinic acid was shown to be most labile to basic hydrolysis. We additionally show that the acyl migration process is strongly pH dependent with increased transesterification taking place at basic pH. Under dry roasting conditions acyl migration competes with dehydration to form lactones. We argue that acyl migration precedes lactonization, with 3-caffeoylquinic acid lactone being the predominant product. PMID- 25116432 TI - Phylogeny reconstruction and hybrid analysis of populus (Salicaceae) based on nucleotide sequences of multiple single-copy nuclear genes and plastid fragments. AB - Populus (Salicaceae) is one of the most economically and ecologically important genera of forest trees. The complex reticulate evolution and lack of highly variable orthologous single-copy DNA markers have posed difficulties in resolving the phylogeny of this genus. Based on a large data set of nuclear and plastid DNA sequences, we reconstructed robust phylogeny of Populus using parsimony, maximum likelihood and Bayesian inference methods. The resulting phylogenetic trees showed better resolution at both inter- and intra-sectional level than previous studies. The results revealed that (1) the plastid-based phylogenetic tree resulted in two main clades, suggesting an early divergence of the maternal progenitors of Populus; (2) three advanced sections (Populus, Aigeiros and Tacamahaca) are of hybrid origin; (3) species of the section Tacamahaca could be divided into two major groups based on plastid and nuclear DNA data, suggesting a polyphyletic nature of the section; and (4) many species proved to be of hybrid origin based on the incongruence between plastid and nuclear DNA trees. Reticulate evolution may have played a significant role in the evolution history of Populus by facilitating rapid adaptive radiations into different environments. PMID- 25116443 TI - Robust image registration of biological microscopic images. AB - Image registration of biological data is challenging as complex deformation problems are common. Possible deformation effects can be caused in individual data preparation processes, involving morphological deformations, stain variations, stain artifacts, rotation, translation, and missing tissues. The combining deformation effects tend to make existing automatic registration methods perform poor. In our experiments on serial histopathological images, the six state of the art image registration techniques, including TrakEM2, SURF + affine transformation, UnwarpJ, bUnwarpJ, CLAHE + bUnwarpJ and BrainAligner, achieve no greater than 70% averaged accuracies, while the proposed method achieves 91.49% averaged accuracy. The proposed method has also been demonstrated to be significantly better in alignment of laser scanning microscope brain images and serial ssTEM images than the benchmark automatic approaches (p < 0.001). The contribution of this study is to introduce a fully automatic, robust and fast image registration method for 2D image registration. PMID- 25116441 TI - The ruthenium nitric oxide donor, [Ru(HEDTA)NO], inhibits acute nociception in mice by modulating oxidative stress, cytokine production and activating the cGMP/PKG/ATP-sensitive potassium channel signaling pathway. AB - Nitric oxide plays an important role in various biological processes including antinociception. The control of its local concentration is crucial for obtaining the desired effect and can be achieved with exogenous nitric oxide-carriers such as ruthenium complexes. Therefore, we evaluated the analgesic effect and mechanism of action of the ruthenium nitric oxide donor [Ru(HEDTA)NO] focusing on the role of cytokines, oxidative stress and activation of the cyclic guanosine monophosphate/protein kinase G/ATP-sensitive potassium channel signaling pathway. It was observed that [Ru(HEDTA)NO] inhibited in a dose-dependent (1-10 mg/kg) manner the acetic acid-induced writhing response. At the dose of 1 mg/kg, [Ru(HEDTA)NO] inhibited the phenyl-p-benzoquinone-induced writhing response, and formalin- and complete Freund's adjuvant-induced licking and flinching responses. Systemic and local treatments with [Ru(HEDTA)NO] also inhibited the carrageenin induced mechanical hyperalgesia and increase of myeloperoxidase activity in paw skin samples. Mechanistically, [Ru(HEDTA)NO] inhibited carrageenin-induced production of the hyperalgesic cytokines tumor necrosis factor-alpha and interleukin-1beta, and decrease of reduced glutathione levels. Furthermore, the inhibitory effect of [Ru(HEDTA)NO] in the carrageenin-induced hyperalgesia and myeloperoxidase activity was prevented by the treatment with ODQ (soluble guanylyl cyclase inhibitor), KT5823 (protein kinase G inhibitor) and glybenclamide (ATP-sensitive potassium channel inhibitor), indicating that [Ru(HEDTA)NO] inhibits inflammatory hyperalgesia by activating the cyclic guanosine monophosphate/protein kinase G/ATP-sensitive potassium channel signaling pathway, respectively. These results demonstrate that [Ru(HEDTA)NO] exerts its analgesic effect in inflammation by inhibiting pro-nociceptive cytokine production, oxidative imbalance and activation of the nitric oxide/cyclic guanosine monophosphate/protein kinase G/ATP-sensitive potassium channel signaling pathway in mice. PMID- 25116444 TI - Serum Dickkopf-1 expression level positively correlates with a poor prognosis in breast cancer. AB - BACKGROUND: The different expression level of Dickkopf-1 (DKK-1) in different cancers shows that the function of DKK-1 depends on the histological type of the cancer cells and the tissue microenvironment. To our knowledge, the serum expression level of DKK-1 in breast cancer is little known. METHODS: Blood samples from 125 consecutive patients diagnosed with breast cancer and 53 control subjects from March 2008 to August 2013 were investigated. Serum DKK-1 expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The overall survival (OS) and relapse-free survival (RFS) analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. RESULTS: The mean serum level of DKK-1 in patients with breast cancer was 4.99 +/- 1.50 ng/mL, and was significantly higher than that in healthy individuals (1.88 +/- 0.81 ng/mL, P < 0.001). DKK-1 level correlated significantly with TNM stage (P = 0.009), tumor grade (P = 0.02), lymph node metastasis (P = 0.001), and expression of HER2 (P = 0.002). The DKK-1 expression level was classified as high or low in relation to the median value, and patients with breast cancer (n = 125) were divided into a high expression group (n = 63) and a low expression group (n = 62). The Kaplan Meier method for survival analysis showed that the patients with a high serum DKK 1 level had a poorer OS (48.7% vs. 81.3%, p = 0.01) and RFS (24.3% vs. 71.6%, p = 0.003) than those with a low expression level. The multivariate Cox regression analysis indicated that serum DKK-1 level was independent prognostic factors for OS and RFS. CONCLUSIONS: Serum DKK-1 level can be used as a noninvasive biomarker for the prognosis of breast cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_161. PMID- 25116446 TI - Clinical utility of an observation and response chart with human factors design characteristics and a track and trigger system: study protocol for a two-phase multisite multiple-methods design. AB - BACKGROUND: Clinical deterioration of adult patients in acute medical-surgical wards continues to occur, despite a range of systems and processes designed to minimize this risk. In Australia, a standardized template for adult observation charts using human factors design principles and decision-support characteristics was developed to improve the detection of and response to abnormal vital signs. OBJECTIVE: To describe the study protocol for the clinical testing of these observation and response charts (ORCs). METHODS: We propose a two-phase multisite multiple-methods design to test the initial clinical utility of the charts in 10 hospitals of differing types and sizes across state jurisdictions in Australia. Data collection in the first phase includes user surveys, observations and field notes by project officers, handover de-briefs (short interviews with small groups of staff), and an audit of ORC documentation completion compared to the site's existing observation chart. For the second phase, data will be collected using a retrospective audit of observation documentation from the previous hospital observation chart, prospective audit of observation documentation following implementation of the selected ORC, user focus groups, observational field notes, and patient outcome data from routinely collected organizational data sources. RESULTS: Site selection and preparation, project officer training, chart selection and implementation, participant recruitment, and data collection has been completed and the analysis of these results are in progress. CONCLUSIONS: This detailed description of these study methods and data collection approaches will enable a comprehensive assessment of the clinical utility of these newly developed track and trigger charts and will be useful for clinicians and researchers when planning and implementing similar studies. Potential methodological limitations are also noted. PMID- 25116447 TI - Oxidative stress and biochemical responses in the tissues of African catfish Clarias gariepinus juvenile following exposure to primextra herbicide. AB - Primextra is a commercial herbicide formulation generally used in agriculture for weed control. The present study was designed to investigate the oxidative stress biomarkers and biochemical responses in the tissues of Clarias gariepinus juvenile exposed to primextra. Fish were exposed to 0.24 and 0.47 mgL(-1) corresponding to 1/20 and 1/10th of 96 h LC50 of the herbicide. The liver and muscle tissues were sampled on day 1, 5, 10 and 15 and results showed concentration and time dependent significant increase (p < 0.05) in the values of lipid peroxidation, glutathione peroxidase, catalase and alkaline phosphatase in both tissues. A marked significant increase (p < 0.05) was observed in the values of aspartate aminotransferase, alanine aminotransferase and glucose in the liver while a mixed trend in their values were observed in the muscle. The values of superoxide dismutase and protein in both tissues were comparable to the control except on day 15 in the liver where the values significantly declined. The condition factor was not directly affected but values of hepatosomatic index were significantly reduced. The present findings revealed that primextra induced toxic stress even at sublethal concentrations resulting in alterations of the studied parameters which were more evident in the fish liver than in the muscle tissue. PMID- 25116448 TI - Effect of internal structure of collagen/hydroxyapatite scaffold on the osteogenic differentiation of mesenchymal stem cells. AB - Consisting of seed cells and scaffold, regenerative medicine provides a new way for the repair and regeneration of tissue and organ. Collagen/hydroxyapatite (HA) biocomposite scaffold is highlighted due to its advantageous features of two major components of bone matrix: collagen and HA. The aim of this study is to investigate the effect of internal structure of collagen/HA scaffold on the fate of rat mesenchymal stem cells (MSCs). The internal structure of collagen/HA scaffold was characterized by micro-CT. It is found that the porosity decreased while average compressive modulus increased with the increase of collagen proportion. Within the collagen proportion of 0.35%, 0.5% and 0.7%, the porosities were 89.08%, 78.37% and 75.36%, the pore sizes were 140.6+/-75.5 MUm, 133.9+/-48.4 MUm and 160.7+/-119.6 MUm, and the average compressive moduli were 6.74+/-1.16 kPa, 8.82+/-2.12 kPa and 23.61+/-8.06 kPa, respectively. Among these three kinds of scaffolds, MSCs on the Col 0.35/HA 22 scaffold have the highest viability and the best cell proliferation. On the contrary, the Col 0.7/HA 22 scaffold has the best ability to stimulate MSCs to differentiate into osteoblasts in a relatively short period of time. In vivo research also demonstrated that the internal structure of collagen/HA scaffold has significant effect on the cell infiltration. Therefore, precise control of the internal structure of collagen/HA scaffold can provide a more efficient carrier to the repair of bone defects. PMID- 25116449 TI - Role of signaling pathways in mesenchymal stem cell differentiation. AB - Mesenchymal Stem Cells (MSCs) are self-renewing cells with ability to differentiate into organized, functional network of cells. In recent past research in developing clinical applications for MSCs has increased significantly. MSCs exhibit multi potential proliferation, and are capable of differentiating into cartilage, bone, neuronal cells and adipocytes, etc. Signaling pathways, transcription factors and growth factors modulate the differentiation of MSCs into different cell lineages. Besides, physical factors may regulate the molecular differentiation of stem cells. The main theme of this paper is to review the signaling pathways related to bone morphogenetic proteins (BMPs), epidermal growth factors (EGF), transforming growth factors (TGF), wingless type MMTV integration site (wnt) proteins, fibroblastic growth factor (FGF), and transcriptional regulating factors significance in the MSCs differentiation. PMID- 25116450 TI - Role of inflammation and tumor microenvironment in the development of gastrointestinal cancers: what induced pluripotent stem cells can do? AB - Connections between inflammation and cancer are a rapidly developing field. Some gastrointestinal tract cancers arise from infection, chronic irritation, and ensuing inflammation. Cellular effectors and mediators are important constituents of the tumor microenvironment, including neoplastic, stromal, and migratory hematopoietic cells. Complex interaction between these cells in the tumor microenvironment regulates tumor growth, progression, metastasis, and angiogenesis. Tumor-associated macrophages represent the major inflammatory cell population in tumors, which orchestrate various aspects of cancer. Cytokines and chemokines are major mediators of communication between cells in the tumor microenvironment. The concept of oncogene builds up an inflammatory pre neoplastic microenvironment has emerged in the last few years. On the other hand, the development of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research. However, there are still some debates about iPSCs which should be answered by science. PMID- 25116451 TI - Toxicological analysis and antihyperalgesic, antidepressant, and anti inflammatory effects of Campomanesia adamantium fruit barks. AB - OBJECTIVE: This study evaluates the anti-inflammatory, antihyperalgesic, and antidepressive potential of the hydroalcoholic extract of Campomanesia adamantium fruit barks (CAE) on rodents and determines the safety of this plant. METHODS: The acute toxicity of CAE was evaluated by oral administration to female rats as single doses of 0, 500, 1000, or 2000 mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. In the subacute toxicity test, male and female rats received 125 or 250 mg/kg body weight of CAE for 28 days. The oral anti-inflammatory activity of CAE was evaluated in carrageenan-induced pleurisy in male mice. The effect of treatment with CAE (100 mg/kg) for 15 days was evaluated in mechanical hyperalgesia (electronic von Frey), depressive behavior (forced swimming test), and cold hypersensitivity in spared nerve injury (SNI) model in rats. RESULTS: No clinical signs of toxicity were observed in animals from the experimental groups during acute and subacute exposure to CAE. At pleurisy test, the oral administration of CAE significantly inhibited leukocyte migration and protein leakage at all doses tested when compared to control. Oral administration of CAE for 3-15 days significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. Finally, on the 15th day, oral treatment with CAE prevented the increase in sensitivity to a cold stimulus induced by SNI. DISCUSSION: The present study shows that C. adamantium extract has anti-inflammatory, antihyperalgesic, and antidepressive properties in rodents without causing toxicity. PMID- 25116452 TI - Functional regulation of neuronal nitric oxide synthase expression and activity in the rat retina. AB - In the nervous system within physiological conditions, nitric oxide (NO) production depends on the activity of nitric oxide synthases (NOSs), and particularly on the expression of the neuronal isoform (nNOS). In the sensory systems, the role of NO is poorly understood. In this study, we identified nNOS positive cells in the inner nuclear layer (INL) of the rat retina, with distinct characteristics such as somata size, immunolabeling level and location. Employing mathematical cluster analysis, we determined that nNOS amacrine cells are formed by two distinct populations. We next investigated the molecular identity of these cells, which did not show colocalization with calbindin (CB), choline acetyltransferase (ChAT), parvalbumin (PV) or protein kinase C (PKC), and only partial colocalization with calretinin (CR), revealing the accumulation of nNOS in specific amacrine cell populations. To access the functional, circuitry related roles of these cells, we performed experiments after adaptation to different ambient light conditions. After 24h of dark-adaptation, we detected a subtle, yet statistically significant decrease in nNOS transcript levels, which returned to steady-state levels after 24h of normal light-dark cycle, revealing that nNOS expression is governed by ambient light conditions. Employing electron paramagnetic resonance (EPR), we demonstrated that dark-adaptation decreases NO production in the retina. Furthermore, nNOS accumulation changed in the dark adapted retinas, with a general reduction in the inner plexiform layer. Finally, computational analysis based on clustering techniques revealed that dark adaptation differently affected both types of nNOS-positive amacrine cells. Taken together, our data disclosed functional regulation of nNOS expression and activity, disclosing new circuitry-related roles of nNOS-positive cells. More importantly, this study indicated unsuspected roles for NO in the sensory systems, particularly related to adaptation to ambient demands. PMID- 25116453 TI - Binding mode analysis of a major T3SS translocator protein PopB with its chaperone PcrH from Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa, a Gram-negative pathogen uses a specialized set of Type III secretion system (T3SS) translocator proteins to establish virulence in the host cell. An understanding of the factors that govern translocation by the translocator protein-chaperone complex is thus of immense importance. In this work, experimental and computational techniques were used to probe into the structure of the major translocator protein PopB from P. aeruginosa and to identify the important regions involved in functioning of the translocator protein. This study reveals that the binding sites of the common chaperone PcrH, needed for maintenance of the translocator PopB within the bacterial cytoplasm, which are primarily localized within the N-terminal domain. However, disordered and flexible residues located both at the N- and C-terminal domains are also observed to be involved in association with the chaperone. This intrinsic disorderliness of the terminal domains is conserved for all the major T3SS translocator proteins and is functionally important to maintain the intrinsically disordered state of the translocators. Our experimental and computational analyses suggest that a "disorder-to-order" transition of PopB protein might take place upon PcrH binding. The long helical coiled-coil part of PopB protein perhaps helps in pore formation while the flexible apical region is involved in chaperone interaction. Thus, our computational model of translocator protein PopB and its binding analyses provide crucial functional insights into the T3SS translocation mechanism. PMID- 25116445 TI - Targeted nanotechnology for cancer imaging. AB - Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID- 25116454 TI - Tackle-related injury rates and nature of injuries in South African Youth Week tournament rugby union players (under-13 to under-18): an observational cohort study. AB - OBJECTIVES: The tackle situation is most often associated with the high injury rates in rugby union. Tackle injury epidemiology in rugby union has previously been focused on senior cohorts but less is known about younger cohorts. The aim of this study was to report on the nature and rates of tackle-related injuries in South African youth rugby union players representing their provinces at national tournaments. DESIGN: Observational cohort study. SETTING: Four South African Youth Week tournaments (under-13 Craven Week, under-16 Grant Khomo Week, under-18 Academy Week, under-18 Craven Week). PARTICIPANTS: Injury data were collected from 3652 youth rugby union players (population at risk) in 2011 and 2012. OUTCOME MEASURES: Tackle-related injury severity ('time-loss' and 'medical attention'), type and location, injury rate per 1000 h (including 95% CIs). Injury rate ratios (IRR) were calculated and modelled using a Poisson regression. A chi(2) analysis was used to detect linear trends between injuries and increasing match quarters. RESULTS: The 2012 under-13 Craven Week had a significantly greater 'time-loss' injury rate when compared with the 2012 under 18 Academy Week (IRR=4.43; 95% CI 2.13 to 9.21, p<0.05) and under-18 Craven Week (IRR=3.52; 95% CI 1.54 to 8.00, p<0.05). The Poisson regression also revealed a higher probability of 'overall' ('time-loss' and 'medical attention' combined) and 'time-loss' tackle-related injuries occurring at the under-13 Craven Week. The proportion of 'overall' and 'time-loss' injuries increased significantly with each quarter of the match when all four tournaments were combined (p<0.05). CONCLUSIONS: There was a difference in the tackle-related injury rate between the under-13 tournament and the two under-18 tournaments, and the tackle-related injury rate was higher in the final quarter of matches. Ongoing injury surveillance is required to better interpret these findings. Injury prevention strategies targeting the tackle may only be effective once the rate and nature of injuries have been accurately determined. PMID- 25116456 TI - The positive pharmacy care law: an area-level analysis of the relationship between community pharmacy distribution, urbanity and social deprivation in England. AB - OBJECTIVES: To: (1) determine the percentage of the population in England that have access to a community pharmacy within 20 min walk; (2) explore any relationship between the walking distance and urbanity; (3) explore any relationship between the walking distance and social deprivation; and (4) explore any interactions between urbanity, social deprivation and community pharmacy access. DESIGN: This area level analysis spatial study used postcodes for all community pharmacies in England. Each postcode was assigned to a population lookup table and lower super output area (LSOA). The LSOA was then matched to urbanity (urban, town and fringe or village, hamlet and isolated dwellings) and deprivation decile (using the Index of Multiple Deprivation score). PRIMARY OUTCOME MEASURE: Access to a community pharmacy within 20 min walk. RESULTS: Overall, 89.2% of the population is estimated to have access to a community pharmacy within 20 min walk. For urban areas, that is 98.3% of the population, for town and fringe, 79.9% of the population, while for rural areas, 18.9% of the population. For areas of lowest deprivation (deprivation decile 1) 90.2% of the population have access to a community pharmacy within 20 min walk, compared to 99.8% in areas of highest deprivation (deprivation decile 10), a percentage difference of 9.6% (8.2, 10.9). CONCLUSIONS: Our study shows that the majority of the population can access a community pharmacy within 20 min walk and crucially, access is greater in areas of highest deprivation--a positive pharmacy care law. More research is needed to explore the perceptions and experiences of people- from various levels of deprivation--around the accessibility of community pharmacy services. PMID- 25116455 TI - Can training in advanced clinical skills in obstetrics, neonatal care and leadership, of non-physician clinicians in Malawi impact on clinical services improvements (the ETATMBA project): a process evaluation. AB - OBJECTIVES: The 'enhancing human resources and the use of appropriate technologies for maternal and perinatal survival in sub-Saharan Africa' (ETATMBA) project is training emergency obstetric and new-born care (EmONC) non-physician clinicians (NPCs) as advanced clinical leaders. Our objectives were to evaluate the implementation and changes to practice. DESIGN: A mixed methods process evaluation with the predominate methodology being qualitative. SETTING: Rural and urban hospitals in 8 of the 14 districts of northern and central Malawi. PARTICIPANTS: 54 EmONC NPCs with 3 years' plus experience. INTERVENTION: Training designed and delivered by clinicians from the UK and Malawi; it is a 2-year plus package of training (classroom, mentorship and assignments). RESULTS: We conducted 79 trainee interviews over three time points during the training, as well as a convenience sample of 10 colleagues, 7 district officers and 2 UK obstetricians. Trainees worked in a context of substantial variation in the rates of maternal and neonatal deaths between districts. Training reached trainees working across the target regions. For 46 trainees (8 dropped out of the course), dose delivered in terms of attendance was high and all 46 spent time working alongside an obstetrician. In early interviews trainees recalled course content unprompted indicating training had been received. Colleagues and district officers reported cascading of knowledge and initial changes in practice indicating early implementation. By asking trainees to describe actual cases we found they had implemented new knowledge and skills. These included life-saving interventions for postpartum haemorrhage and eclampsia. Trainees identified the leadership training as enabling them to confidently change their own practice and initiate change in their health facility. CONCLUSIONS: This process evaluation suggests that trainees have made positive changes in their practice. Clear impacts on maternal and perinatal mortality are yet to be elucidated. PMID- 25116457 TI - Arterial stiffness and wave reflection 1 year after a pregnancy complicated by hypertension. AB - Hypertensive disorders of pregnancy (HDP) are associated with cardiovascular disease (CVD) later in life. The authors investigated the association of HDP with blood pressure (BP) and arterial stiffness 1-year postpartum. Seventy-four participants, 33 with an HDP and 41 with uncomplicated pregnancies, were examined using applanation tonometry to measure BP, carotid-femoral pulse wave velocity (cfPWV), and augmentation index (AIx). On average, women with HDP had a 9 mm higher systolic BP (P<.01), 0.8 m/s faster cfPWV (P=.09), and 5.4% greater AIx (P=.09) at the 1-year examination. After adjustment for covariates, there was no significant difference in cfPWV between groups, while a 7.3% greater AIx (P<.05) remained. These findings suggest that reduced endothelial function may be detected 1 year after HDP. Large prospective studies are needed to further understand the contribution of arterial stiffness and endothelial dysfunction in the evolution of CVD after these complicated pregnancies. PMID- 25116459 TI - Papillary thyroid microcarcinoma in a thyroid pyramidal lobe. AB - We report an extremely rare case of papillary thyroid microcarcinoma (PTMC) in the thyroid Epub ahead of print pyramidal lobe (TPL). A 48-year-old woman underwent ultrasound-guided fine-needle aspiration for a small thyroid nodule in the right lobe in local clinic, and it revealed a malignant cytology. On preoperative ultrasonography for tumor staging in our hospital, another small suspiciously malignant hypoechoic nodule was detected in the left TPL. Total thyroidectomy and central nodal dissection were performed. Histopathology confirmed PTMCs in the left TPL and both thyroid lobes. Ultrasonography for TPL should be required for complete evaluation of possible multifocality of thyroid malignancy. PMID- 25116460 TI - Theoretical study on reaction mechanism of ground-state cyano radical with 1,3 butadiene: prospect of pyridine formation. AB - The reaction of ground-state cyano radicals, CN(X(2)Sigma(+)), with the simplest polyene, 1,3-butadiene (C4H6(X(1)Ag)), is investigated to explore probable routes and feasibility to form pyridine at ultralow temperatures. The isomerization and dissociation channels for each of the seven initial collision complexes are characterized by utilizing the unrestricted B3LYP/cc-pVTZ and the CCSD(T)/cc-pVTZ calculations. With facilitation of RRKM rate constants, through ab initio paths composed of 7 collision complexes, 331 intermediates, 62 hydrogen atom, 71 hydrogen molecule, and 3 hydrogen cyanide dissociated products, the most probable paths at collision energies up to 10 kcal/mol, and thus the reaction mechanism, are determined. Subsequently, the corresponding rate equations are solved that the concentration evolutions of collision complexes, intermediates, and products versus time are obtained. As a result, the final products and yields are determined. The low-energy routes for the formation of most thermodynamically stable product, pyridine, are identified. This study, however, predicts that seven collision complexes would produce predominately 1-cyano-1,3-butadiene, CH2CHCHCHCN (p2) plus atomic hydrogen via the collision complex c1(CH2CHCHCH2CN) and intermediate i2(CH2CHCH2CHCN), with a very minor amount of pyridine. Our scheme also effectively excludes the presence of 2-cyano-1,3-butadiene, which has energy near-degenerate to 1-cyano-1,3-butadiene, as supported by experimental findings. PMID- 25116458 TI - Fetal tumors: prenatal ultrasonographic findings and clinical characteristics. AB - The incidence of fetal tumors has been increased due to generalization of prenatal evaluation and improvement of imaging techniques. The early detection of a fetal tumor and understanding of its imaging features are very important for fetal, maternal, and neonatal care. Ultrasonography is usually used for the detection and differential diagnosis of fetal tumors, and magnetic resonance imaging is increasingly being used as a complementary study. Many fetal tumors have different clinical and imaging features compared with pediatric tumors. Although several fetal tumors may mimic other common anomalies, some specific imaging features may carry early accurate diagnosis of fetal tumors, which may alter the prenatal management of a pregnancy and the mode of delivery, and facilitate immediate postnatal treatment. PMID- 25116461 TI - The effectiveness of the cognitive behavioral analysis system of psychotherapy for chronic depression: a randomized controlled trial. AB - BACKGROUND: It is widely agreed that chronic depression is difficult to treat, knowledge about optimal treatment approaches is emerging. METHOD: A multisite randomized controlled trial was conducted comparing the cognitive behavioral analysis system of psychotherapy (CBASP), a psychotherapy model developed specifically to treat chronic depression (n = 67) with care as usual (CAU; evidence-based treatments, n = 72) over a period of 52 weeks, with 23 sessions on average, in 3 outpatient clinics in the Netherlands. In both arms algorithm-based pharmacotherapy was provided. Patients (aged 18-65) met criteria for a DSM-IV diagnosis of major depressive disorder with diagnostic specifiers (chronic, without interepisode recovery) or with co-occurring dysthymic disorder indicating a chronic course. The Inventory for Depressive Symptomatology (IDS) Self-Report was used as the primary outcome measure. Mixed-effects linear regression analysis was used to compare the changes on the IDS scores between CBASP and CAU. The IDS was administered before treatment, and after 8, 16, 32 and 52 weeks. RESULTS: At week 52, patients assigned to CBASP had a greater reduction of depressive symptoms compared to patients assigned to CAU (t = -2.00, p = 0.05). However, CBASP and CAU did not differ from each other on the IDS after 8 weeks (t = 0.49, p = 0.63), 16 weeks (t = -0.03, p = 0.98) and 32 weeks (t = -0.17, p = 0.86) of treatment. CONCLUSIONS: This trial shows that CBASP is at least as effective as standard evidence-based treatments for chronic depression. In the long run, CBASP appears to have an added effect. PMID- 25116463 TI - Isolated right-sided mural infective endocarditis in a 32-year-old woman with muscular ventricular septal defect. AB - Bacterial endocarditis secondary to jet streams from a congenital heart defect without valvular involvement is very rare, especially in adult patients. We report an unusual case of a 32-year-old woman with a previously known unrepaired ventricular septal defect (VSD) who presented with intermittent fever and chills after dental treatment and was diagnosed with isolated right-sided mural infective endocarditis associated with a muscular-type VSD. Echocardiography revealed a low echogenic, mobile vegetation along the right ventricular outflow tract (RVOT) free wall and a small-sized muscular-type VSD. The patient's blood culture grew Streptococcus viridians. After 3 weeks of antibiotic treatment, VSD patch closure was performed, and the vegetation on the RVOT endomyocardium was removed. PMID- 25116464 TI - Clinical features and treatment results of children with diffuse large B-cell lymphoma. AB - The demographic, clinical characteristics, and treatment groups of 33 children with diffuse large B-cell lymphoma (DLBCL) were recorded and analyzed among 1486 non-Hodgkin lymphoma (NHL) cases since 1972. The median age was 9.7 years (range 1.4-16.9) and male/female ratio was 24/9 = 2.6. Kaplan-Meier methods and logrank tests were used in treatment analysis. The frequency of DLBCL among 1486 NHL cases was 2.2%, however, the percentage was 9.3% in cases diagnosed after 2000. The event-free survival (EFS) and overall survival (OS) rates for 33 children were 61% and 65.1% at 5 years, respectively. The EFS and OS rates of low stage (stages I and II) disease decreased to lower level in advanced stage (stages III and IV) disease. Associated conditions and ages older than 14 years were found as poor prognostic factors in multivariate analysis. The survival rates in children with DLBCL need further improvement. This is mainly related with late referral of those children with advanced disease. The proper diagnosis and early referral is essential in these children for a better survival rate. The children with associated conditions and older children must be handled with care since these are found as poor prognostic factors. PMID- 25116466 TI - Midwives' personal experiences of pregnancy and childbirth: Exploring issues of autonomy and agency in relation to the use of professional knowledge. AB - This paper seeks to explore midwives' experiences of pregnancy and childbirth. It draws on interviews with nine midwives who completed their midwifery training prior to becoming mothers, to discuss how midwives use their professional knowledge to exercise agency (the choices made about their own care), and assume autonomy (the control and responsibility in relation to their own care), in pregnancy and childbirth. It illustrates that a reliance on professional knowledge may create opportunities for choice and increased autonomy in some situations, although the need for intervention during childbirth, for example, may challenge the degree of autonomy exercised by midwives and the choices available to them. As knowledgeable experts, midwives demonstrate a very different understanding of risk and safety in relation to their own experiences of childbirth. Professional knowledge may increase their anxieties which may not be addressed appropriately by caregivers due to their professional status. The use of knowledge in this way highlights potential conflict between their position as midwives and their experience as mothers, illustrating that midwives' ability to exercise agency and autonomy in relation to their pregnancy and childbirth experiences is potentially problematic. PMID- 25116465 TI - Biomarkers of dissolved oxygen stress in oysters: a tool for restoration and management efforts. AB - The frequency and intensity of anoxic and hypoxic events are increasing worldwide, creating stress on the organisms that inhabit affected waters. To understand the effects of low dissolved oxygen stress on oysters, hatchery-reared oysters were placed in cages and deployed along with continuously recording environmental data sondes at a reef site in Mobile Bay, AL that typically experiences low oxygen conditions. To detect and measure sublethal stress, we measured growth and survival of oysters as well as expression of three biomarkers, heat shock protein 70 (HSP70), hypoxia inducible factor (HIF) and phospho-p38 MAP kinase, in tissues from juvenile and adult oysters. Survival rates were high for both juvenile and adult oysters. Expression levels of each of the 3 isoforms of HSP 70 were negatively correlated to dissolved oxygen (DO) concentrations, suggesting that HSP 70 is useful to quantify sublethal effects of DO stress. Results for HIF and phospho-p38 MAP kinase were inconclusive. Test deployments of oysters to assess expression of HSP 70 relative to environmental conditions will be useful, in addition to measuring abiotic factors, to identify appropriate sites for restoration, particularly to capture negative effects of habitat quality on biota before lethal impacts are incurred. PMID- 25116468 TI - Diruthenium-polyyn-diyl-diruthenium wires: electronic coupling in the long distance regime. AB - Reported herein is a series of Ru2(Xap)4 capped polyyn-diyl compounds, where Xap is either 2-anilinopyridinate (ap) or its aniline substituted derivatives. Symmetric [Ru2(Xap)4](MU-C4k)[Ru2(Xap)4] (compounds 4ka (X = 3-isobutoxy) and 4kc (X = 3,5-dimethoxy) with k = 2, 3, 4, and 5) was obtained from the Glaser coupling reaction of Ru2(Xap)4(C2kH). Unsymmetric [Ru2(Xap)4](MU C(4k+2))[Ru2(ap)4] (compounds 4k+2b with k = 2, 3, and 4) were prepared from the Glaser coupling reaction between Ru2(Xap)4(C(2k+2)H) and Ru2(ap)4(C2kH). X-ray diffraction study of compound 12c revealed both the sigmoidal topology of the polyyn-diyl bridge and the fine structural detail about the Ru2 cores. Cyclic and differential pulse voltammetric (CV and DPV) measurements and spectroelectrochemical studies revealed that (i) the reduced monoanions [Ru2-C2m Ru2](-1) (m = 4-8) belong to the Robin-Day class II mixed valent ions and (ii) the electronic coupling between Ru2 termini depends on the length of the polyyn diyl bridge with an attenuation constant (gamma) between 0.12 and 0.15 A(-1). In addition, spin-unrestricted DFT calculations provide insight about the nature of orbitals that mediate the long distance electronic coupling. PMID- 25116467 TI - Radial glia phagocytose axonal debris from degenerating overextending axons in the developing olfactory bulb. AB - Axon targeting during the development of the olfactory system is not always accurate, and numerous axons overextend past the target layer into the deeper layers of the olfactory bulb. To date, the fate of the mis-targeted axons has not been determined. We hypothesized that following overextension, the axons degenerate, and cells within the deeper layers of the olfactory bulb phagocytose the axonal debris. We utilized a line of transgenic mice that expresses ZsGreen fluorescent protein in primary olfactory axons. We found that overextending axons closely followed the filaments of radial glia present in the olfactory bulb during embryonic development. Following overextension into deeper layers of the olfactory bulb, axons degenerated and radial glia responded by phagocytosing the resulting debris. We used in vitro analysis to confirm that the radial glia had phagocytosed debris from olfactory axons. We also investigated whether the fate of overextending axons was altered when the development of the olfactory bulb was perturbed. In mice that lacked Sox10, a transcription factor essential for normal olfactory bulb development, we observed a disruption to the morphology and positioning of radial glia and an accumulation of olfactory axon debris within the bulb. Our results demonstrate that during early development of the olfactory system, radial glia play an important role in removing overextended axons from the deeper layers of the olfactory bulb. PMID- 25116469 TI - Tuning CO2 selective adsorption over N2 and CH4 in UiO-67 analogues through ligand functionalization. AB - Introducing functional groups into pores of metal-organic frameworks (MOFs) through ligand modification provides an efficacious approach for tuning gas adsorption and separation performances of this type of novel porous material. In this work, two UiO-67 analogues, [Zr6O4(OH)4(FDCA)6] (BUT-10) and [Zr6O4(OH)4(DTDAO)6] (BUT-11), with functionalized pore surfaces and high stability were synthesized from two functional ligands, 9-fluorenone-2,7 dicarboxylic acid (H2FDCA) and dibenzo[b,d]thiophene-3,7-dicarboxylic acid 5,5 dioxide (H2DTDAO), respectively, and structurally determined by single-crystal X ray diffraction. Notwithstanding skeleton bend of the two ligands relative to the linear 4,4'-biphenyldicarboxylic acid in UiO-67, the two MOFs have structures similar to that of UiO-67, with only lowered symmetry in their frameworks. Attributed to these additional functional groups (carbonyl and sulfone, respectively) in the ligands, BUT-10 and -11 show enhanced CO2 adsorption and separation selectivities over N2 and CH4, in spite of decreased pore sizes and surface areas compared with UiO-67. At 298 K and 1 atm, the CO2 uptake is 22.9, 50.6, and 53.5 cm(3)/g, and the infinite dilution selectivities of CO2/CH4 are 2.7, 5.1, and 9.0 and those of CO2/N2 are 9.4, 18.6, and 31.5 for UiO-67, BUT-10, and BUT-11, respectively. The selectivities of CO2/CH4 and CO2/N2 are thus enhanced 1.9 and 2.0 times in BUT-10 and 3.3 and 3.4 times in BUT-11, respectively, on the basis of UiO-67. The adsorption mechanism of CO2 in BUT-11 has also been explored through computational simulations. The results show that CO2 molecules locate around the sulfone groups in pore surfaces of BUT-11, verifying at the molecular level that sulfone groups significantly increase the affinity toward CO2 molecules of the framework. This provides thus an efficient strategy for the design of CO2 capture materials. PMID- 25116470 TI - Anisotropic magnetoresistance state space of permalloy nanowires with domain wall pinning geometry. AB - The domain wall-related change in the anisotropic magnetoresistance in L-shaped permalloy nanowires is measured as a function of the magnitude and orientation of the applied magnetic field. The magnetoresistance curves, compiled into so-called domain wall magnetoresistance state space maps, are used to identify highly reproducible transitions between domain states. Magnetic force microscopy and micromagnetic modelling are correlated with the transport measurements of the devices in order to identify different magnetization states. Analysis allows to determine the optimal working parameters for specific devices, such as the minimal field required to switch magnetization or the most appropriate angle for maximal separation of the pinning/depinning fields. Moreover, the complete state space maps can be used to predict evolution of nanodevices in magnetic field without a need of additional electrical measurements and for repayable initialization of magnetic sensors into a well-specified state. PMID- 25116471 TI - Long-term effects of growth hormone replacement therapy on liver function in adult patients with growth hormone deficiency. AB - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are frequently observed in patients with adult growth hormone deficiency (AGHD) and short-term GH replacement therapy (GHRT) has reportedly been efficacious in NAFLD and NASH. The aim of this study was to investigate whether long-term GHRT is an effective treatment for the hepatic comorbidities in AGHD. DESIGN: This is a retrospective observational study. We recruited 54 consecutive hypopituitary patients with AGHD. Among them, 31 patients who had received GHRT for more than 24 months were compared with 19 age- and sex-matched patients without GHRT. We also analyzed the long term effect of GHRT on 14 patients diagnosed with NASH by liver biopsy. In addition, we subdivided the GHRT group into GH-responder and GH-non-responder groups and analyzed the factors associated with the efficacy of the treatment. RESULTS: For a period of 24 months, the significant reduction of serum liver enzyme levels and a fibrotic marker was observed in patients receiving GHRT compared with the control group. Furthermore, GHRT also improved liver enzyme levels in AGHD patients with NASH. The GH-non-responder group showed a higher proportion of patients who gained weight during the study period. CONCLUSIONS: These results indicate that GHRT is efficacious for improving serum liver enzyme levels for at least 24 months in patients with AGHD. To optimize this effect, it is important to avoid body weight gain during the treatment. PMID- 25116472 TI - Autosomal recessive form of isolated growth hormone deficiency is more frequent than the autosomal dominant form in a Brazilian cohort. AB - BACKGROUND: In most studies, the autosomal dominant (type II) form of isolated growth hormone deficiency (IGHD) has been more frequent than the autosomal recessive (type I) form. Our aim was to assess defects in the GH1 in short Brazilian children with different GH secretion status. SUBJECTS AND METHODS: We selected 135 children with postnatal short stature and classified according to the highest GH peak at stimulation tests in: severe IGHD (peak GH<=3.3 MUg/L, n=38, all with normal pituitary magnetic resonance imaging); GH peak between 3.3 and 10 MUg/L (n=76); and GH peak >10 MUg/L (n=21). The entire coding region of GH1 was sequenced and complete GH1 deletions were assessed by Multiplex Ligation Dependent Probe Amplification and restriction enzyme digestion. RESULTS: Patients with severe IGHD had a higher frequency of consanguinity, were shorter, had lower levels of IGF-1 and IGFBP-3, and despite treatment with lower GH doses had a greater growth response than patients with GH peak >=3.3 MUg/L. Mutations were found only in patients with severe IGHD (GH peak<3.3 MUg/L). Eight patients had autosomal recessive IGHD: Seven patients were homozygous for GH1 deletions and one patient was compound heterozygous for a GH1 deletion and the novel c.171+5G>C point mutation in intron 2, predicted to abolish the donor splice site. Only one patient, who was heterozygous for the c.291+1G>T mutation located at the universal donor splice site of intron 3 and predicts exon 3 skipping, had an autosomal dominant form. CONCLUSION: Analysis of GH1 in a cohort of Brazilian patients revealed that the autosomal recessive form of IGHD was more common than the dominant one, and both were found only in severe IGHD. PMID- 25116476 TI - Activated-ester-type photocleavable crosslinker for preparation of photodegradable hydrogels using a two-component mixing reaction. AB - Photodegradable hydrogels have emerged as powerful platforms for studying and directing cellular behavior in a spatiotemporally controlled manner. Photodegradable hydrogels have previously been formed by free radical polymerizations, Michael-type addition reactions, and orthogonal click reactions. Here, an ester-activated photocleavable crosslinker is presented for preparing photodegradable hydrogels by means of a one-step mixing reaction between the crosslinker and a biocompatible polymer containing amino moieties (amino terminated tetra-arm poly(ethylene glycol) or gelatin). It is demonstrated that photodegradable hydrogels micropatterned by photolithography can be used to culture cells with high viability and proliferation rates. The resulting micropatterned cell-laden structures can potentially be used to create 3D biomaterials for various tissue-engineering applications. PMID- 25116477 TI - Controlling the enzymatic digestion of lipids using hybrid nanostructured materials. AB - Solid nanoparticle-lipid hybrids have been engineered by using spray drying to assemble monodisperse hydrophilic silica nanoparticles and submicron lipid (triglyceride) emulsions together into composite microparticles, which have specific activity toward enzymes. The influence of silica particle size (100-1000 nm) and emulsifier type (anionic and cationic) on the three-dimensional structure of the composite particles was investigated. The nanostructure of the hybrid particles, which is controlled by the size of the voids between the closely packed silica particles, plays a critical role in lipase action and hence lipid digestion kinetics. Confining lipid droplets within the nanostructured silica aggregates led to 2- to 15-fold enhanced rate of lipolysis in comparison with dispersed coarse oil droplets. The composite particles were tailored to enhance, retain or sustain the lipolysis kinetics of submicron lipid emulsions. The presence of repulsive nanoparticle-droplet interactions favored aqueous redispersion and fast lipolysis of the hybrid composite materials, while attractive interactions hindered redispersion and delayed lipolysis of the confined lipid droplets. Such hybrid nanomaterials can be exploited to control the gastrointestinal enzymatic action and promisingly form the basis for the next generation of foods and medicines. PMID- 25116473 TI - Fgfr1 inactivation in the mouse telencephalon results in impaired maturation of interneurons expressing parvalbumin. AB - Fibroblast growth factors (Fgfs) and their receptors (Fgfr) are expressed in the developing and adult CNS. Previous studies demonstrated a decrease in cortical interneurons and locomotor hyperactivity in mice with a conditional Fgfr1 deletion generated in radial glial cells during midneurogenesis (Fgfr1(f/f);hGfapCre+). Here, we report earlier and more extensive inactivation of Fgfr1 in neuroepithelial cells of the CNS (Fgfr1(f/f);NesCre+). Similar to findings in Fgfr1(f/f);hGfapCre+ mice, parvalbumin positive (PV+) cortical interneurons are also decreased in the neocortex of Fgfr1(f/f);NesCre+ mice when compared to control littermates (Fgfr1(f/f)). Fgfr1(f/f);NesCre+ embryos do not differ from controls in the initial specification of GABAergic cells in the ganglionic eminence (GE) as assessed by in situ hybridization for Dlx2, Mash1 and Nkx2. Equal numbers of GABAergic neuron precursors genetically labeled with green fluorescent protein (GFP) were observed at P0 in Fgfr1(f/f);hGfapCre+;Gad1-GFP mutant mice. However, fewer GFP+ and GFP+/PV+ interneurons were observed in these mutants at adulthood, indicating that a decrease in cortical interneuron markers is occurring postnatally. Fgfr1 is expressed in cortical astrocytes in the postnatal brain. To test whether the astrocytes of mice lacking Fgfr1 are less capable of supporting interneurons, we co-cultured wild type Gad1-GFP+ interneuron precursors isolated from the medial GE (MGE) with astrocytes from Fgfr1(f/f) control or Fgfr1(f/f);hGfapCre+ mice. Interneurons grown on Fgfr1 deficient astrocytes had small soma size and fewer neurites per cell, but no differences in cell survival. Decreased soma size of Gad67 immunopositive interneurons was also observed in the cortex of adult Fgfr1(f/f);NesCre+ mice. Our data indicate that astrocytes from Fgfr1 mutants are impaired in supporting the maturation of cortical GABAergic neurons in the postnatal period. This model may elucidate potential mechanisms of impaired PV interneuron maturation relevant to neuropsychiatric disorders that develop in childhood and adolescence. PMID- 25116478 TI - Physics of nanomechanical spectrometry of viruses. AB - There is an emerging need of nanotools able to quantify the mechanical properties of single biological entities. A promising approach is the measurement of the shifts of the resonant frequencies of ultrathin cantilevers induced by the adsorption of the studied biological systems. Here, we present a detailed theoretical analysis to calculate the resonance frequency shift induced by the mechanical stiffness of viral nanotubes. The model accounts for the high surface to-volume ratio featured by single biological entities, the shape anisotropy and the interfacial adhesion. The model is applied to the case in which tobacco mosaic virus is randomly delivered to a silicon nitride cantilever. The theoretical framework opens the door to a novel paradigm for biological spectrometry as well as for measuring the Young's modulus of biological systems with minimal strains. PMID- 25116480 TI - Effect of pH and recombinant barley (Hordeum vulgare L.) endoprotease B2 on degradation of proteins in soaked barley. AB - Nonfermented soaking of barley feedstuff has been established as an in vitro procedure prior to the feeding of pigs as it can increase protein digestibility. In the current study, two feed cultivars of barley (Finlissa and Zephyr) were soaked in vitro either nonbuffered or buffered at pH 3.6 and 4.3. Solubilized and degraded proteins evaluated by biuret, SDS-PAGE, and differential proteomics revealed that pH 4.3 had the greatest impact on both solubilization and degradation. In order to boost proteolysis, the recombinant barley endoprotease B2 (rec-HvEP-B2) was included after 8 h using the pH 4.3 regime. Proteolysis evaluated by SDS-PAGE and differential proteomics confirmed a powerful effect of adding rec-HvEP-B2 to the soaked barley, regardless of the genotype. Our study addresses the use of rec-HvEP-B2 as an effective feed enzyme protease. HvEP-B2 has the potential to increase the digestibility of protein in the pig, either supplied as recombinant additive or as possible new selection criterion in barley breeding. PMID- 25116479 TI - Porcine epidemic diarrhea virus RNA present in commercial spray-dried porcine plasma is not infectious to naive pigs. AB - Porcine epidemic diarrhea virus emerged in North America in April 2013 and has since been identified in 30 U.S. States, Canada and Mexico. The rapid spread of PEDV has raised concerns about the role of feed and particularly pork-by-product components such as spray-dried porcine plasma (SDPP) in PEDV transmission. The aim of this study was to determine the infectivity of PEDV RNA present in commercial SDPP. Specifically, 40 3-week-old PEDV naive pigs were randomly assigned to one of five treatment groups. At day post inoculation (dpi) 0, NEG CONTROL pigs were sham-inoculated, PEDV-CONTROL pigs received cell culture propagated PEDV, and SDPP-CONTROL pigs were switched to a diet with 5% SDPP containing 5.1+/-0.1 log10 PEDV RNA copies/g. To evaluate a potential positive effect of anti-PEDV antibodies in SDPP on PEDV challenge, four days prior to PEDV challenge the pigs in the SDPP-PEDV group were switched to and remained on a 5% SDPP diet through dpi 28. Another group, EGG-PEDV, was orally administered a commercial egg-derived liquid PEDV globulin product from dpi -4 through 6. All PEDV-CONTROL pigs began shedding PEDV in feces by dpi 3 and seroconverted between dpi 7 and 14, whereas pigs in NEG-CONTROL and SDPP-CONTROL groups remained PEDV RNA negative and did not seroconvert to PEDV for the study duration. This indicates no evidence of infectivity of the PEDV RNA in the SDPP lot utilized. Furthermore, under the study conditions SDPP or egg-derived liquid PEDV globulin addition did not significantly alter PEDV-shedding or overall disease course after experimental challenge. PMID- 25116481 TI - Safety, pharmacokinetic, and positron emission tomography evaluation of serotonin and dopamine transporter occupancy following multiple-dose administration of the triple monoamine reuptake inhibitor BMS-820836. AB - RATIONALE: BMS-820836 is a novel antidepressant that selectively inhibits the reuptake of serotonin, norepinephrine, and dopamine. OBJECTIVE: This Phase I study assessed safety, tolerability, and pharmacokinetics of multiple daily doses of BMS-820836 in healthy subjects. Central serotonin transporter (SERT) and dopamine transporter (DAT) occupancy were assessed using positron emission tomography and [(11)C]MADAM or [(11)C]PE2I, respectively. METHODS: Fifty-seven healthy volunteers were enrolled in this double-blind, placebo-controlled, ascending multiple-dose study (ClincalTrials.gov identifier: NCT00892840). Eight participants in seven dose cohorts received oral doses of BMS-820836 (0.1-4 mg) or placebo for 14 days to assess safety, tolerability, and pharmacokinetics. Additionally, SERT and DAT occupancies were evaluated in 4-8 subjects per cohort at 8 h post-dose on Day 10 and 24 h post-dose on Day 15 at anticipated steady state conditions. RESULTS: Most adverse events were mild to moderate; there were no serious safety concerns. Median maximum concentrations of BMS-820836 were observed at 4.0-5.5 h post-dose; estimated elimination half-life was 44-74 h. About 80 % striatal SERT occupancy was achieved after multiple doses of 0.5 mg BMS-820836 at both 8 and 24 h post-dose. Striatal DAT occupancy ranged between 14 % and 35 % at 8 h post-dose with a slight decline at 24 h post-dose. CONCLUSIONS: Multiple daily doses of up to 4 mg BMS-820836 appeared to be generally safe and well tolerated in a healthy population. SERT and DAT occupancies were in a range associated with therapeutic efficacy of antidepressants. Together with the pharmacokinetic profile of BMS-820836, the occupancy data support once-daily administration. PMID- 25116484 TI - Research on the infiltration processes of lawn soils of the Babao River in the Qilian Mountain. AB - Using a Guelph Permeameter, the soil water infiltration processes were analyzed in the Babao River of the Qilian Mountain in China. The results showed that the average soil initial infiltration and the steady infiltration rates in the upstream reaches of the Babao River are 1.93 and 0.99 cm/min, whereas those of the middle area are 0.48 cm/min and 0.21 cm/min, respectively. The infiltration processes can be divided into three stages: the rapidly changing stage (0-10 min), the slowly changing stage (10-30 min) and the stabilization stage (after 30 min). We used field data collected from lawn soils and evaluated the performances of the infiltration models of Philip, Kostiakov and Horton with the sum of squared error, the root mean square error, the coefficient of determination, the mean error, the model efficiency and Willmott's index of agreement. The results indicated that the Kostiakov model was most suitable for studying the infiltration process in the alpine lawn soils. PMID- 25116482 TI - Cognitive judgment bias in the psychostimulant-induced model of mania in rats. AB - RATIONALE: Animal models of mania lack genuine cognitive parameters. The present gold standard of mania models, amphetamine-induced hyperlocomotion, is rather unspecific and does not necessarily target its cardinal symptoms. Therefore, alternative behavioral markers that are sensitive to stimulants are required. OBJECTIVES: In the present study, by combining the psychostimulant-induced model of mania in rodents with the recently developed ambiguous-cue interpretation (ACI) tests, we investigated the effects of chronic administration of D amphetamine and cocaine on the cognitive judgment bias of rats. METHODS: To accomplish this goal, in two separate experiments, previously trained animals received chronic, daily injections of either D-amphetamine (2 mg/kg) or cocaine (10 mg/kg) for 2 weeks and were subsequently tested with the ACI procedure. RESULTS: Chronic treatment with both psychostimulants did not make rats more "optimistic." CONCLUSIONS: The results are discussed in terms of behavioral and pharmacological actions of the tested compounds and their implications for modeling mania in animals. PMID- 25116485 TI - Retainment of the antimicrobial agent triclosan in a septic tank. AB - Laboratory experiments were conducted to investigate the fate of the antimicrobial agent triclosan (TCS) in a conventional septic tank. The main mechanism of TCS removal from wastewater was identified to be rapid TCS sorption to suspended particles followed by settling of these particles to the bottom of the septic tank. Sorption to particles was completed within minutes while the settling took several days. Therefore, in a septic tank the removal of TCS from wastewater is mainly determined by the removal of suspended particles by sedimentation. Over 5 days of hydraulic residence time the initial dissolved TCS concentration of 100 MUg L(-1) was reduced by 87 +/- 8%. During the first 24 hours, 66-86% of all removed TCS was retained, whereas during the remainder of the experiment a slight but steady decrease in TCS concentration was observed. This was most likely caused by TCS diffusion and its subsequent sorption onto the septic sludge. PMID- 25116483 TI - Reduced dopamine release in the nucleus accumbens core of adult rats following adolescent binge alcohol exposure: age and dose-dependent analysis. AB - RATIONALE: Alcohol use in adolescence is one of the most significant predictors of alcohol dependence in adulthood, yet the neurochemical mechanisms underlying this heightened vulnerability remain unknown. Whereas research has focused on characterizing adaptations in the mesolimbic dopamine (DA) system following ethanol exposure in adolescence, whether these changes persist into adulthood has yet to be determined. OBJECTIVES: The objective of this study is to investigate the effects of binge-intermittent ethanol administration in adolescence (P30-50) or early adulthood (P60-80) on DA in the nucleus accumbens (NAc) core after an ethanol challenge in adulthood following a period of abstinence. METHODS: Male Sprague Dawley rats (n = 160) were administered intermittent ethanol injections, 1 or 3 g/kg, intraperitoneally (i.p.) every other day for 20 days starting on either P30 or 60. Following an ethanol-free period of either 7, 14, or 28 days, we measured DA efflux following an ethanol challenge (3 g/kg, i.p.) using electrochemical recording electrodes bilaterally implanted into the NAc core. RESULTS: Moderate-dose ethanol administration (1 g/kg, i.p.) during adolescence significantly decreased ethanol-evoked DA release in adulthood at 7 and 14 days, but not 28 days, following pretreatment exposure compared to saline controls. Relative to rats pretreated with ethanol in adulthood, moderate-dose ethanol in adolescence significantly reduced DA efflux at all time points measured. Additionally, adult rats pretreated with high dose ethanol administration (3 g/kg, i.p.) displayed significantly decreased DA compared to adolescents after 28 days of withdrawal. CONCLUSIONS: Binge-intermittent ethanol administration during adolescence may induce age-dependent neuroadaptations in the mesolimbic DA system compared to ethanol-treated adults during protracted ethanol withdrawal. PMID- 25116486 TI - Effect of pH on phosphorus, copper, and zinc elution from swine wastewater activated sludge. AB - With the goal of reducing the amounts of phosphorus (P), copper (Cu), and zinc (Zn) discharged from swine wastewater activated sludge treatment facilities, we studied the elution of these elements from activated sludge at various pH values. Sludge samples with neutral pH collected from three farms were incubated at pH values ranging from 3 to 10. The soluble concentrations of these elements changed dramatically with pH and were highest at pH 3. We assumed that P present in the sludge under neutral and alkaline conditions was in insoluble form bound up with magnesium (Mg) and calcium (Ca), because Ca and Mg also eluted from the sludge at low pH. To clarify forms of Zn and Cu in the sludge, we performed a sequential extraction analysis. Zinc in adsorbed, organically bound, and sulfide fractions made up a large proportion of the total Zn. Copper in organically bound, carbonate, and sulfide fractions made up a large proportion of the total Cu. The soluble P concentrations were lowest at pH 9 or 10 (11-36 mg/L), the soluble Zn concentrations were lowest at pH 8 or 9 (0.07-0.15 mg/L), and the soluble Cu concentrations were lowest at pH 6-9 (0.2 mg/L, the detection limit). PMID- 25116487 TI - Determination of methane yield of cellulose using different experimental setups. AB - In this work, biochemical methane potential (BMP) tests with cellulose as a model substrate were performed with the aid of three manually operated or conventional experimental setups (based on manometer, water column and gas bag) and one automated apparatus specially designed for analysis of BMP. The methane yields were 340 +/- 18, 354 +/- 13, 345 +/- 15 and 366 +/- 5 ml CH4/g VS obtained from experimental setups with manometer, water column, gas bag, and automatic methane potential test system, which corresponded to a biodegradability of 82, 85, 83 and 88% respectively. The results demonstrated that the methane yields of cellulose obtained from conventional and automatic experimental setups were comparable; however, the methane yield obtained from the automated apparatus showed greater precision. Moreover, conventional setups for the BMP test were more time- and labour-intensive compared with the automated apparatus. PMID- 25116488 TI - Cloud point extraction-flame atomic absorption spectrometry method for preconcentration and determination of trace cadmium in water samples. AB - A method based on cloud point extraction (CPE) separation/preconcentration of trace cadmium (Cd) as a prior step to its determination by flame atomic absorption spectrometry has been developed. Cadmium reacted with 8 hydroxyquinoline to form hydrophobic chelates, which were extracted into the micelles of nonionic surfactant oligoethylene glycol monoalkyl ether (Genapol X 080) in an alkaline medium. Octanol was used to depress the cloud point of Genapol X-080 in the extraction process. The chemical variables that affect the CPE, such as pH of complexation reaction, amount of chelating agent, Genapol X 080 and octanol were evaluated and optimized. Under optimized conditions, linearity was obeyed in the range of 10-500 MUg/L, with the correlation coefficient of 0.9993. For 5 mL of sample solution, the enhancement factor was about 20. The limit of detection and limit of quantification of the method were 0.21 and 0.63 MUg/L, respectively. The relative standard deviations (n = 6) was 3.2% for a solution containing 100 MUg/L of Cd. The accuracy of the preconcentration system was evaluated by recovery measurements on spiked water samples. Recoveries of spiked samples varied in the range of 94.1-103.8%. PMID- 25116489 TI - Characterization of water pollution in drainage networks using continuous monitoring data in the Citadel area of Hue City, Vietnam. AB - In the Citadel area of Hue City, drainage systems that include canals and ponds are considerable sources of fecal contaminants to inundated water during the rainy season because canals and ponds receive untreated wastewater. It is important to investigate the characteristics of hydraulics and water pollution in canals and ponds. At the canals and ponds, water sampling was conducted during dry and wet weather periods in order to evaluate fecal contamination and to investigate changes in water pollution caused by runoff inflow. Inundated water was also collected from streets during heavy rainfall. At the canals and ponds, concentrations of Escherichia coli and total coliform exceeded the Vietnamese regulation values for surface water in 23 and 24 out of 27 samples (85 and 89%), respectively. The water samples were categorized based on the characteristics of water pollution using cluster analysis. In the rainy season, continuous monitoring was conducted at the canals and ponds using water depth and electrical conductivity (EC) sensors to investigate the dynamic relationship between water level and water pollution. It is suggested that in the canals, high EC meant water stagnation and low EC signified river water inflow. Therefore, EC might be a good indicator of water flow change in canals. PMID- 25116490 TI - Removal of fluoride and arsenic by pilot vertical-flow constructed wetlands using soil and coal cinder as substrate. AB - This study evaluated the performance of soil and coal cinder used as substrate in vertical-flow constructed wetlands for removal of fluoride and arsenic. Two duplicate pilot-scale artificial wetlands were set up, planted respectively with cannas, calamus and no plant as blank, fed with a synthetic sewage solution. Laboratory (batch) incubation experiments were also carried out separately to ascertain the fluoride and arsenic adsorption capacity of the two materials (i.e. soil and coal cinder). The results showed that both soil and coal cinder had quite high fluoride and arsenic adsorption capacity. The wetlands were operated for two months. The concentrations of fluoride and arsenic in the effluent of the blank wetlands were obviously higher than in the other wetlands planted with cannas and calamus. Fluoride and arsenic accumulation in the wetlands body at the end of the operation period was in range of 14.07-37.24% and 32.43-90.04%, respectively, as compared with the unused media. PMID- 25116491 TI - Visualized study on the interaction between single bubbles and curved solid surface in flotation separation process. AB - The present study has been devoted to bubble-curved solid surface interaction in water, which is critical to the separation of suspended particles by air flotation. For this purpose, two particular stages of the interaction (collision and attachment) have been examined visually using high-speed photography in a laboratory-scale flotation column. The effects of the surface material and surfactant concentration on these two stages have been also studied quantitatively. The considered solid materials are the cleaned glass as hydrophilic surface and Teflon as hydrophobic surface. The experimental results show that the presence of surfactant significantly affects the collision and rebound process of a gas bubble, while there is no obvious effect of the surface material on the rebound process. An increase in surfactant concentration has been observed to suppress the rebound number and maximal distance of the bubble from the surface. Moreover, the three-phase contact time of the bubble is a strong function of the surfactant concentration and surface hydrophobicity as well as of the bubble diameter. Another important finding is that the bubble attachment is only observed at the hydrophobic Teflon surface below the surfactant CMC (critical micelle concentration). Results of this study are relevant for deep understanding of the attachment mechanism and to determine the proper conditions for a selective flotation process. PMID- 25116492 TI - Assessment of the impact of traditional septic tank soakaway systems on water quality in Ireland. AB - One of the key threats to groundwater and surface water quality in Ireland is the impact of poorly designed, constructed or maintained on-site wastewater treatment systems. An extensive study was carried out to quantify the impact of existing sites on water quality. Six existing sites, consisting of a traditional septic tank and soakaway system, located in various ranges of subsoil permeabilities were identified and monitored to determine how well they function under varying subsoil and weather conditions. The preliminary results of the chemical and microbiological pollutant attenuation in the subsoil of the systems have been assessed and treatment performance evaluated, as well as impact on local surface water and groundwater quality. The source of any faecal contamination detected in groundwater, nearby surface water and effluent samples was confirmed by microbial source tracking. From this, it can be seen that the transport and treatment of percolate vary greatly depending on the permeability and composition of the subsoil. PMID- 25116493 TI - Removal of toluene from water by photocatalytic oxidation with activated carbon supported Fe(3+)-doped TiO2 nanotubes. AB - In this work, activated carbon (AC)-supported TiO2 containing 1.0% (mass percent) of 1.0 at.% (atomic percent) Fe(3+)-doped TiO2 nanotubes (Fe-TNTs) were successfully synthesized. The catalyst was used to effectively decompose toluene in water under O3/UV conditions, and some properties including the morphology, X ray photoelectron spectroscopy, X-ray diffraction patterns, specific surface area and UV-visible diffuse reflectance spectroscopy were analyzed. A removal efficiency of 90.7% was achieved in the presence of fresh AC-supported Fe-TNTs calcined at 550 degrees C, with a pseudo-first-order rate constant of 0.038/min. The removal efficiency of toluene was reduced when the catalysts were repeatedly used, since the amount of adsorption sites of the supporting substrates decreased. However, even after AC-supported catalyst was used four times, the removal efficiency of toluene was still sufficient in water treatment. The enhanced photocatalytic activity of AC-supported Fe-TNTs was related to the synergistic effect of AC adsorption and Fe-TNTs photocatalytic ozonation. The water from a petrochemical company in China was used to obtain the removal efficiency of the pollutants, and the toluene and total organic carbon removal efficiencies were 69.9% and 58.3%, respectively. PMID- 25116494 TI - Study of competitive adsorption of acid dyes on magnetic quaternary chitosan salt. AB - Magnetic quaternary chitosan salt CS/EPTAC/Fe3O4 was used for the removal of acid red 1 (AR1), xylenol orange (XO) and alizarin red (AR) in single, binary and ternary systems. In the single system, the maximal adsorption capacity was 781.55 for AR1, 537.40 for XO and 992.61 mg g(-1) for AR at pH 3.0 and 25 degrees C. The adsorption kinetics of the three dyes followed the pseudo-second-order model. In the multicomponent system, preferential adsorption was observed for AR at low adsorbent quantities due to the small size of the molecule. When the adsorbent amount was greater, AR1 was adsorbed first because of the greater number of sulfonic acid roots. In the entire adsorption process, XO always adsorbed most slowly. PMID- 25116495 TI - Development of a down-flow hanging sponge reactor for the treatment of low strength sewage. AB - The process performance of a down-flow hanging sponge (DHS) reactor for treating low strength sewage (biochemical oxygen demand (BOD) 20-50 mg/L) was investigated in Bangkok, Thailand. The hydraulic retention time (HRT) was set at 4 h during the start-up period and was reduced to 1.5 h in a stepwise manner. Throughout the 300-day operational period, the DHS reactor shows high performance with respect to the removal of total suspended solid (>90% total suspended solid removal efficiency). No clogging of sponge media was observed in response to the self digestion phenomena of the biofilm. At a HRT of 1.5 h, the BOD removal efficiency was sufficiently high (about 85%). The pathogen Escherichia coli and other coliform bacteria were removed almost completely as well (removal was 99.4% and 98.1%, respectively). Regarding the retained sludge activity measurement, the nitrite oxidation rate was higher than the ammonium oxidation rate (0.031 and 0.022 gram of nitrogen per gram of volatile suspended solids per day, respectively). In the 300 days of operation, the amount of excess sludge production was negligible. Thus, no sludge treatment system is required. Introduction of the DHS system in developing countries is recommended because this system requires a relatively small area, and has low electricity consumption and operation costs. PMID- 25116496 TI - Adsorption of hexavalent chromium onto organic bentonite modified by the use of iron(III) chloride. AB - The adsorption of hexavalent chromium (Cr(VI)) was improved by using organic bentonite (OB) modified with iron(III) chloride. The adsorption mechanisms and characteristics of OB and organic bentonite modified by FeCl3 (FMOB) were studied by using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy (EDS). It was found that hydroxyl-iron replaced some of the calcium and magnesium contained in the FMOB, but no significant change in its structure was shown even though the adsorption experiments proved that FMOB had a better Cr(VI) adsorption ability compared to OB. The coated material was prepared by mixing FMOB and 4A molecular sieves in a coated pot for the adsorption experiments in the test column. The relevant results showed that the adsorption of the coated material retained its high adsorption ability and maintained that ability after desorption and regeneration, which implied a potential for further application. PMID- 25116497 TI - Impacts of urbanization on river system structure: a case study on Qinhuai River Basin, Yangtze River Delta. AB - Stream structure is usually dominated by various human activities over a short term. An analysis of variation in stream structure from 1979 to 2009 in the Qinhuai River Basin, China, was performed based on remote sensing images and topographic maps by using ArcGIS. A series of river parameters derived from river geomorphology are listed to describe the status of river structure in the past and present. Results showed that urbanization caused a huge increase in the impervious area. The number of rivers in the study area has decreased and length of rivers has shortened. Over the 30 years, there was a 41.03% decrease in river length. Complexity and stability of streams have also changed and consequently the storage capacities of river channels in intensively urbanized areas are much lower than in moderately urbanized areas, indicating a greater risk of floods. Therefore, more attention should be paid to the urban disturbance to rivers. PMID- 25116498 TI - Removal of hexavalent chromium from aqueous solution using exfoliated polyaniline/montmorillonite composite. AB - Exfoliated polyaniline/montmorillonite (PANI/MMT) composites with nanosheet structure were successfully prepared by in situ chemical oxidation polymerization with MMT platelets as the scaffold. Amphoteric polymer, (2 methacryloyloxyethyl)trimethyl ammonium chloride and methacrylate acid copolymer, was used to modify montmorillonite and a large number of carboxylic acids were introduced on the surface of the clay platelets, which can be used as a dopant of PANI and play a 'bridge' role to combine PANI with clay. Adsorption experiments were carried out to study the effects of pH, contact time, Cr(VI) concentration, adsorbent dose and temperature. The adsorption of Cr(VI) on the PANI/MMT was highly pH dependent and the adsorption kinetics followed a pseudo-second-order model. The Langmuir isothermal model described the adsorption isotherm data well and the maximum adsorption capacity increased with the increase in temperature. Thermodynamic investigation indicated that the adsorption process is spontaneous, endothermic and marked with an increase in randomness at the adsorbent - liquid interface. The maximum adsorption capacity of the PANI/MMT composites for Cr(VI) was 308.6 mg/g at 25 degrees C. The excellent adsorption characteristic of exfoliated PANI/MMT composites will render it a highly efficient and economically viable adsorbent for Cr(VI) removal. PMID- 25116499 TI - Migration and transformation behavior of volatile phenol in the vadose zone. AB - Research on the migration and transformation of phenol with space and temporal variability in the vadose zone is hindered by monitoring technology in field experiments. Four column experiments were conducted to investigate the effect of porous media size, volatilization, biological effects, and oxidation on the transport of phenol in the vadose zone. The initial inflow phenol concentration of each column was 500 mg/L, and the final outflow concentrations were 0, 348, 240, and 365 mg/L, More than 90% of reduction of phenol concentration occurred at the top of the simulation column. Results show that volatilization and oxidation are the main factors that could lead to the decrease of phenol concentration in an open system. However, these two processes cannot be accurately separated. The migration rate of phenol was larger in coarse sands (6.06 cm/d) than in fine sands (4.55 cm/d). Phenol biodegradation did not occur under experimental conditions. However, mercury (as biological inhibitor) could react with phenol to generate a mercury-phenol complex, which could lead to the reduction of phenol concentration to 21.6% in the simulation experiment. PMID- 25116500 TI - A novel control strategy for efficient biological phosphorus removal with carbon limited wastewaters. AB - This work shows the development and the in silico evaluation of a novel control strategy aiming at successful biological phosphorus removal in a wastewater treatment plant operating in an A(2)/O configuration with carbon-limited influent. The principle of this novel approach is that the phosphorus in the effluent can be controlled with the nitrate setpoint in the anoxic reactor as manipulated variable. The theoretical background behind this control strategy is that reducing nitrate entrance to the anoxic reactor would result in more organic matter available for biological phosphorus removal. Thus, phosphorus removal would be enhanced at the expense of increasing nitrate in the effluent (but always below legal limits). The work shows the control development, tuning and performance in comparison to open-loop conditions and to two other conventional control strategies for phosphorus removal based on organic matter and metal addition. It is shown that the novel proposed strategy achieves positive nutrient removal results with similar operational costs to the other control strategies and open-loop operation. PMID- 25116501 TI - Evaluation of biotreatability of ionic liquids in aerobic and anaerobic conditions. AB - The aim of our study was to set up an approach for reliable biotreatability assessment of ionic liquids (ILs). As a case study, two different ILs were selected: pyridinium-based 1-butyl-3-methylpyridinium dicyanamide ([bmpyr][dca]) and imidazolium-based 1-butyl-3-methylimidazole tetrafluoroborate ([bmim][BF4]). Toxicity in aerobic conditions was determined by measurement of inhibition of oxygen consumption by activated sludge, while their biodegradability was calculated from measurements of oxygen consumption and dissolved organic carbon elimination. For their biotreatability in anaerobic conditions, the method with measurement of biogas production has been employed comparing flocculent and granular sludge. Both ILs were less toxic and more biodegradable in anaerobic conditions. IL [bmpyr][dca] was not toxic to granular sludge up to 742 mg L(-1) and it even has been degraded at this concentration in the presence of easily degradable glucose. Flocculent sludge was completely inhibited at the lower concentration of 318 mg L(-1), but it degraded by 44% at 106 mg L(-1) in the presence of glucose, indicating the appearance of cometabolism. IL [bmim][BF4] was less toxic but also resistant to biodegradation in anaerobic conditions. It degraded via cometabolism 21% at 1,452 mg L(-1). It has been concluded that any assessment of biotreatability of ILs should include parallel determination in aerobic and anaerobic conditions. PMID- 25116502 TI - Tertiary treatment for wastewater reuse based on the Daphnia magna filtration - comparison with conventional tertiary treatments. AB - Tertiary treatments are required to permit safe reuse of wastewater. The performance of a new biological tertiary treatment based on the filtration by a population of Daphnia magna was studied and compared with the performance of other conventional tertiary treatments such as coagulation-flocculation, settling tank, disc filtration, sand filtering and ultraviolet (UV) light. The analysis was based on the efficiency in the particle removal and Escherichia coli inactivation. The Daphnia magna treatment reduced the concentration of particles with diameters below 30 MUm by 35%, depending on abiotic parameters such as water temperature and the hydraulic retention time (HRT). The Daphnia magna filtration increased with water temperature for water temperatures >20 degrees C, while it remained constant for water temperatures <20 degrees C. Lower HRTs induced the growth of the Daphnia magna population, maintaining the same water quality. Furthermore, the Daphnia magna treatment inactivated E. coli in 1.2 log units. This inactivation was six times larger than that obtained by the conventional macrofiltration systems analyzed, although lower than the inactivation attained by UV light, which ranged between 1.5 and 4 log units. PMID- 25116503 TI - Investigation of initial pH effects on growth of an oleaginous microalgae Chlorella sp. HQ for lipid production and nutrient uptake. AB - Using microalgae for synchronous biodiesel production and wastewater treatment is a promising technology. The growth, lipid accumulation and nutrient uptake characteristics of an oleaginous microalga Chlorella sp. HQ were evaluated at different initial pH from 5.0 to 11.0. The pH values changed towards neutrality and ended in the range 6.0-9.0 without artificial control. The alkalinity change before 8 days was in accordance with pH changing. The alkalinity increase after 8 days might be due to the nitrate consumption, CO2 absorption and the algal release at stationary phases. The algal maximal cell density and population growth rate increased with initial pH values while the specific growth rate kept high without significant difference. After 30 days, the maximal algal lipid yield reaching 167.5 mg . L(-1) occurred at initial pH of 7.0 and the triacylglycerols content was significantly enhanced to 63.0% at initial pH of 5.0 but with a peak of 54.4 mg . L(-1) at initial pH of 9.0. Furthermore, nutrients were taken up by the alga obviously at all initial pH values. The total nitrogen (TN) and total phosphorus (TP) uptake efficiencies in neutral/alkalic circumstances were larger than that in acid circumstance. The TN and TP were removed by 87.77% and 92.05%, respectively, at initial pH of 7.0. PMID- 25116504 TI - N2O emissions from secondary clarifiers and their contribution to the total emissions of the WWTP. AB - Recent studies have indicated that the emissions of nitrous oxide, N2O, constitute a major part of the carbon footprint of wastewater treatment plants (WWTPs). Denitrification occurring in the secondary clarifier basins has been observed by many researchers, but until now N2O emissions from secondary clarifiers have not been widely reported. The objective of this study was to measure the N2O emissions from secondary clarifiers and weigh the portion they could represent of the overall emissions at WWTPs. Online measurements over several days were carried out at four different municipal WWTPs in Finland in cold weather conditions (March) and in warm weather conditions (June-July). An attempt was made to define the conditions in which N2O emissions from secondary clarifiers may occur. It was evidenced that large amounts of N2O can be emitted from the secondary clarifiers, and that the emissions have long-term variation. It was assumed that part of the N2O released in secondary clarification was originally formed in the activated sludge basin. The emissions from secondary clarification thus seem to be dependent on conditions of the nitrification and denitrification accomplished in the denitrification-nitrification process and on the amount of sludge stored in the secondary clarifiers. PMID- 25116505 TI - Simultaneous autotrophic denitrification and nitrification in a low-oxygen reaction environment. AB - The occurrence of autotrophic denitrification and nitrification activities by ammonia-oxidising bacteria and nitrite-oxidising bacteria is studied in a bioreactor system operable at low-dissolved oxygen (DO) and at variable oxygen influx rates. At a loading of 3.6 mg NH4(+)-N/h into the bioreactor, simultaneous autotrophic denitrification and nitrification contributed to NH4(+)-N removal over oxygen influxes of 2-14 mg O2/h and DO <0.5 mg/L. The maximum autotrophic denitrification (or total-N removal) rates were achieved in a narrow oxygen influx band of 3-5 mg O2/h, where it accounted for up to 36% of NH4(+)-N removal. At oxygen influx >16 mg O2/h and DO >2 mg/L, autotrophic denitrification ceases and roughly 90% of feed NH4(+)-N is oxidised to NOX(-)-N. The stability of total effluent chemical oxygen demand (COD) over the range of oxygen influxes tested confirms the absence of heterotrophic denitrification in the bioreactor. The long solids residence time of the stable biomass zone (21 days) led to production of effluent COD as a result of cell decay, and thus effluent COD was used to calculate more accurately the mean cell residence time. PMID- 25116506 TI - Treatment of textile wastewaters using Eutectic Freeze Crystallization. AB - A water treatment process needs to recover both water and other useful products if the process is to be viewed as being financially and environmentally sustainable. Eutectic Freeze Crystallization (EFC) is one such sustainable water treatment process that is able to produce both pure ice (water) and pure salt(s) by operating at a specific temperature. The use of EFC for the treatment of water is particularly useful in the textile industry because ice crystallization excludes all impurities from the recovered water, including dyes. Also, EFC can produce various salts with the intention of reusing these salts in the process. This study investigated the feasibility of EFC as a treatment method for textile industry wastewaters. The results showed that EFC can be used to convert 95% of the wastewater stream to pure ice (98% purity) and sodium sulfate. PMID- 25116507 TI - Evaluation of non-thermal effects by microwave irradiation in hydrolysis of waste activated sludge. AB - The activation energy (Ea) for waste-activated sludge (WAS) hydrolysis was compared between microwave irradiation (MW) and conventional heating (CH) methods to evaluate the non-thermal effect of MW. The microwave-assisted hydrolysis of WAS was assumed to follow the first-order kinetics on the basis of volatile suspended solids (VSS) conversion to soluble chemical oxygen demand (SCOD) for different initial VSS concentrations. By comparing the VSS decrement and the SCOD increment between MW and CH at different absolute temperatures of 323, 348 and 373 K, the average ratio of VSS conversion to SCOD was determined to range from 1.42 to 1.64 g SCOD/g VSS. These results corresponded to the theoretical value of 1.69 g SCOD/g VSS based on the assumption that the molecular formula of sludge was C10H19O3N. Consequently, the Ea of the MW-assisted WAS hydrolysis was much lower than that of CH for the same temperature conditions. The non-thermal effect of MW in the hydrolysis of WAS could be identified with the lower Ea than that of CH. PMID- 25116508 TI - A health risk assessment of reclaimed municipal wastewater for industrial and miscellaneous use. AB - The study evaluated the safety of reclaimed water using health risk assessment and biotoxicity tests. The reclaimed water was produced from reverse osmosis and used in industrial and miscellaneous purposes. The health risk assessment was conducted based on the concentrations of detectable pollutants in reclaimed water in a hypothetical scenario. The estimated carcinogenic and non-carcinogenic risks are lower than the generally accepted level. Biotoxicity evaluation included three genotoxicity tests, a chronic toxicity test using medaka fishes, and a subchronic toxicity test using mice. The reclaimed water is not genetically toxic, and does not cause significant chronic effects on these model organisms. These results confirm the safety of using reclaimed water from municipal wastewater treatment plants. PMID- 25116510 TI - Carborane functionalization of the aromatic network in chemically-synthesized graphene. AB - The conjugated aromatic system of graphene was used to trap the reactive, boron rich 1,2-carborane cluster. Functionalization of the graphene surface was confirmed by solid-state MAS (11)B NMR spectroscopy and quantified by X-ray photoelectron spectroscopy. This work represents the first confirmed example of direct functionalization of a graphene lattice with carboranes. PMID- 25116509 TI - Examining the sustainment of the Adolescent-Community Reinforcement Approach in community addiction treatment settings: protocol for a longitudinal mixed method study. AB - BACKGROUND: Although evidence-based treatments are considered the gold standard for clinical practice, it is widely recognized that evidence-based treatment implementation in real world practice settings has been limited. To address this gap, the federal government provided three years of funding, training and technical assistance to 84 community-based treatment programs to deliver an evidence-based treatment called the Adolescent-Community Reinforcement Approach (A-CRA). Little is known about whether such efforts lead to long-term A-CRA sustainment after the initial funding ends. METHODS/DESIGN: We will use a longitudinal mixed method data analytic approach to characterize sustainment over time and to examine the factors associated with the extent to which A-CRA is sustained. We will use implementation data collected during the funding period (e.g., organizational functioning, staff certification rates and penetration) and supplement it with additional data collected during the proposed project period regarding implementation quality and the hypothesized predictors of sustainment (i.e., inner and outer contextual variables) collected over three waves from 2013 to 2015 representing program sustainment up to five years post-initial funding. DISCUSSION: Gaining a better understanding of the factors that influence the evidence-based treatment sustainment may lead to more effective dissemination strategies and ultimately improve the quality of care being delivered in community-based addiction treatment settings. PMID- 25116511 TI - Liposomes in topical ophthalmic drug delivery: an update. AB - Topical route of administration is the most commonly used method for the treatment of ophthalmic diseases. However, presence of several layers of permeation barriers starting from the tear film till the inner layers of cornea make it difficult to achieve the therapeutic concentrations in the target tissue within the eye. In order to circumvent these barriers and to provide sustained and targeted drug delivery, tremendous advances have been made in developing efficient and safe drug delivery systems. Liposomes due to their unique structure prove to be extremely beneficial drug carriers as they can entrap both the hydrophilic and hydrophobic drugs. The conventional liposomes had several drawbacks particularly their tendency to aggregate, the instability and leakage of entrapped drug and susceptibility to phagocytosis. Due to this reason, for a long time, liposomes as drug delivery systems did not attract much attention of researchers and clinicians. However, over recent years development of new generation liposomes has opened up new approaches for targeted and sustained drug delivery using liposomes and has rejuvenated the interest of researchers in this field. In this review we present a summary of current literature to understand the anatomical and physiological limitation in achieving adequate ocular bioavailability of topically applied drugs and utility of liposomes in overcoming these limitations. The recent developments related to new generation liposomes are discussed. PMID- 25116513 TI - A functionalized, ethynyl-decorated, tetracobalt(III) cubane molecular catalyst for photoinduced water oxidation. AB - A new tetracobalt(III) cubane 1, carrying functionalized peripheral ethynyl groups, was prepared. Cubane 1 catalyses photoinduced water oxidation, indicating that the ethynyl groups do not negatively affect the catalytic properties of the Co cubane assembly. In contrast, the quantum yield for water oxidation (0.36) is significantly increased with respect to the prototype, simplest species. PMID- 25116512 TI - Enhanced transdermal delivery of luteolin via non-ionic surfactant-based vesicle: quality evaluation and anti-arthritic assessment. AB - Luteolin (LUT) is a promising molecule with potential anti-arthritic activity. This investigation presents formulation and evaluation of niosomal transgel for enhanced transdermal delivery of LUT. Different non-ionic surfactants and vesicle compositions were employed for preparation of niosomes. The vesicle size analysis showed that all vesicles were in the range from 534.58 to 810.22 nm which favoured efficient transdermal delivery. The entrapment of LUT in vesicle was found to be higher in all surfactant. The developed formulation was proved significantly superior in terms of amount of drug permeation with an enhancement ratio of 2.66 when compared to a control formulation. The in vivo bioactivity studies revealed that the prepared niotransgel formulation of LUT was able to provide good anti-arthritic activity and the results were comparable to standard (diclofenac gel for anti-arthritic and analgesic). Finally, the results were confirmed through radiological analysis which proved that the prepared niotransgel was effectively able to treat arthritis and results were comparable with the standard formulation. PMID- 25116515 TI - Continuation of NHS Pay Review body benefits all. AB - The prospect of yet another year in which most nurses' standard of living will fall because the English government is too mean to fund a pay rise could hardly be more depressing. Last week's announcement by the Treasury that nurses will not receive a cost-of-living pay award next year - only a 1 per cent one-off payment if they are at the top of their pay band - demonstrates the lack of respect ministers have for the profession. PMID- 25116514 TI - Solution and crystal structure of BA42, a protein from the Antarctic bacterium Bizionia argentinensis comprised of a stand-alone TPM domain. AB - The structure of the BA42 protein belonging to the Antarctic flavobacterium Bizionia argentinensis was determined by nuclear magnetic resonance and X-ray crystallography. This is the first structure of a member of the PF04536 family comprised of a stand-alone TPM domain. The structure reveals a new topological variant of the four beta-strands constituting the central beta-sheet of the alphabetaalpha architecture and a double metal binding site stabilizing a pair of crossing loops, not observed in previous structures of proteins belonging to this family. BA42 shows differences in structure and dynamics in the presence or absence of bound metals. The affinity for divalent metal ions is close to that observed in proteins that modulate their activity as a function of metal concentration, anticipating a possible role for BA42. PMID- 25116516 TI - 100 years to the day: candlelit vigil at Westminster Abbey. AB - A ceremony attended by nurses marking the centenary of the outbreak of the first world war was held at Westminster Abbey last week. PMID- 25116517 TI - Stafford Hospital witness to advise NHS Freedom to Speak Up review. AB - The nurse who exposed appalling treatment of patients at Stafford Hospital has been enlisted as an adviser to a major review into NHS whistleblowing. PMID- 25116519 TI - Pay rise 'a political issue' as review body ignored. AB - The government is refusing to revisit its decision to deny 70 per cent of nurses a 1 per cent cost of living pay rise next April - despite the looming threat of industrial action by a number of health unions. PMID- 25116520 TI - Nurses in the front line of cuts at HEE. AB - Nearly one third of senior Health Education England (HEE) posts that will be axed to reduce costs are held by nurses, Nursing Standard has learned. PMID- 25116521 TI - Ebola death toll rises in Africa with at least 14 nurses among the dead. AB - At least 14 nurses are among 80 healthcare workers who have died from an outbreak of the Ebola virus spreading across West Africa, declared an international public health emergency last week by the World Health Organization (WHO). PMID- 25116522 TI - Nurse admits to falsifying records. AB - A nurse has pleaded guilty to nine counts of wilful neglect while working at the Princess of Wales Hospital in Bridgend, Wales. PMID- 25116524 TI - Medication patch may help people with schizophrenia. AB - Mental health research nurses are recruiting patients to take part in an ongoing landmark trial to test an antipsychotic medication patch to treat schizophrenia. PMID- 25116525 TI - Staff seek funds in NHS version of Dragons' Den. AB - Nurses and healthcare assistants pitched ideas to improve care in a Dragons' Den style event at Northern Lincolnshire and Goole NHS Foundation Trust last week. PMID- 25116526 TI - Grouping diabetes checks could confuse score and reward process. AB - Diabetes nurses have questioned whether GP practices will have the staff capacity to carry out eight health checks on diabetes patients recommended by the National Institute for Care and Health Excellence (NICE). PMID- 25116527 TI - Volunteer healthcare staff set off to Gaza. AB - Nurses are among a team of 14 health professionals who have gone to Gaza as part of a humanitarian NHS mission. PMID- 25116528 TI - Staffing shortfalls remain an issue at many trusts in special measures. AB - Five trusts that must remain in special measures for another six months have nurse shortages and inadequate leadership that pose a threat to public safety, according to a report by health regulators. PMID- 25116530 TI - Niece visits library that honours nurse killed on WW1 front line. AB - The niece of a nurse killed while caring for injured troops in the first world war has paid an emotional visit to a medical history library named in her aunt's memory. PMID- 25116532 TI - Hospitals told to ban junk food and offer staff incentives to lose weight. AB - Burgers, chips and fatty foods being served up in hospital canteens could soon become a thing of the past, if Simon Stevens gets his way. PMID- 25116538 TI - HIV. AB - Essential facts [Figure: see text] HIV is a virus that weakens the immune system and leaves people less able to fight infection. According to the National Institute for Health and Care Excellence (NICE), an estimated 98,400 people were living with HIV in the UK in 2012, but one in five of them did not know they were carrying the virus. If those people were identified and treated, then a further 3,500 cases of HIV transmission could be prevented within five years. PMID- 25116539 TI - Tired of carrying the burden of fatigue. AB - A high proportion of people with rheumatoid arthritis experience fatigue. This has a severe effect on their wellbeing, yet the symptom is rarely understood and poorly managed by healthcare professionals. Nurses are being urged to recognise the issues and explore effective treatment options with patients. PMID- 25116540 TI - Learn to see patients in their own world. AB - Insights from the social sciences can help nurses understand the influences that shaped their patients and the decisions they make. This can develop empathy and encourage better care. Nurses are passionate about their patients' wellbeing. They can use the social sciences to improve the care they deliver and improve their patients' lives. PMID- 25116541 TI - Royal Naval nursing: 'testing but worth it'. AB - Inga Kennedy is the most senior nurse in the Royal Navy. She enjoys the commitment and discipline required by a career in the armed forces and says the work offers great opportunities for nurses. Her career highlights have included checking that injured personnel in Afghanistan were receiving the best care possible. PMID- 25116552 TI - First Aid for Cyclists app. AB - This new, free app from St John Ambulance gives cyclists the skills to deal with the most common cycling injuries. PMID- 25116554 TI - RCN faces challenges over rising inequalities within profession. AB - It is difficult to understand why the RCN will not join colleagues in the Royal College of Midwives and other health unions in balloting members on industrial action (Editorial and News July 30). Is the RCN fearful of the outcome should the response be a yes? PMID- 25116555 TI - It is time to take industrial action to reverse the sell-off of the NHS. AB - As a nurse at St Thomas' Hospital in London during the strikes in the 1980s, I never wanted to strike, having seen the effects on patient care (Letters May 21). PMID- 25116556 TI - Unite calls on the NMC to reject the proposed 20% fee increase. AB - We at Unite are opposed to the proposal from the Nursing and Midwifery Council (NMC) to increase the registration fee from L100 a year to L120 in March next year (News July 30 and August 6). PMID- 25116557 TI - Remembering Herbert Sulzbach and those who work for peace. AB - As we commemorate those who gave their lives in the first world war, it is important that we also remember those who have worked to foster good relations between former combatants. PMID- 25116560 TI - Looking at people as individuals is vital to any work assessment. AB - I agree with the recent Commons committee report recommending the scrapping, because of design flaws, of the Employment and Support Allowance for people who are unable to work because of disability or sickness (News July 30). PMID- 25116561 TI - Force-feeding is in the interests of the state, not its prisoners. AB - Further to Paul Hegarty's letter, 'Force-feeding is wrong and nurses should play no part' (July 30), the International Council of Nurses is clear about the role of nurses. PMID- 25116562 TI - Service user and carer involvement in pre-registration student selection. AB - An online questionnaire was undertaken to evaluate the involvement of service users and carers in the student selection process and to identify how the pre registration process might be enhanced. Respondents comprised 34 students, all of whom had been selected for the pre-registration nursing education programme following this process, and 22 others, including service users and carers, practitioners, and lecturers, who had been involved in the selection process. A positive attitude to the involvement of service users and carers was evident in all groups, although there were some concerns and suggestions about how and when involvement of service users and carers should occur. The main findings were that service users could have an important role in contextualising mental health in people's lives. PMID- 25116563 TI - Using personal narrative to deepen emotional awareness of practice. AB - Storytelling is intrinsic to human beings, and stories can explain events, stances taken and actions engaged in. When experience is represented as story it can become more organised and be used for analysis, critique and learning. Experience is important in nursing, as it is in many other practice-based professions, and it can contribute much to nurses' learning. Through a process of sharing and engaging with the author's personal stories, this article encourages nurses to begin to organise their own experiences in story form for use in learning and as part of their personal and professional development. PMID- 25116564 TI - Assessment and management of patients with ankle injuries. AB - Foot and ankle injuries are common and can have a significant effect on an individual's daily activities. Nurses have an important role in the assessment, management, ongoing care and support of patients with ankle injuries. An understanding of the anatomy and physiology of the ankle enables nurses to identify significant injuries, which may result in serious complications, and communicate effectively with the multidisciplinary team to improve patient care and outcomes. PMID- 25116565 TI - Acute confusion. AB - Acute confusion, an acute cognitive impairment associated with severe illness, is often termed delirium. Delirium seldom resolves steadily but goes through cycles of improving and then worsening. PMID- 25116568 TI - Bringing the clinic to the class. AB - The transformation of nurse education from diploma to degree has been coupled with greater emphasis on the use of evidence in practice. As a result, teaching staff have been trying to improve the integration of theory and practice learning. PMID- 25116566 TI - Express yourself. AB - Communication has always been a vital part of nursing. As students, we learned about therapeutic communication and the differences between sympathy, empathy, and rapport. I remember struggling with those differences and when to use each most appropriately with patients, families, classmates and lecturers. Now, I apply these principles at work with staff. PMID- 25116569 TI - Sharps practice in focus. AB - The EU Sharps Directive on the prevention of sharps injuries in the healthcare sector (see resources ) was incorporated into the national law of all EU member states on May 11 2013. PMID- 25116570 TI - Student life - African learning experience. AB - Archbishop Desmond Tutu once claimed that TB was the child of poverty, as well as its parent and provider. My first insight into the truth of this came while I was on a placement with Find & Treat, a pan-London tuberculosis (TB) service for vulnerable communities. PMID- 25116571 TI - Larval Population Density Alters Adult Sleep in Wild-Type Drosophila melanogaster but Not in Amnesiac Mutant Flies. AB - Sleep has many important biological functions, but how sleep is regulated remains poorly understood. In humans, social isolation and other stressors early in life can disrupt adult sleep. In fruit flies housed at different population densities during early adulthood, social enrichment was shown to increase subsequent sleep, but it is unknown if population density during early development can also influence adult sleep. To answer this question, we maintained Drosophila larvae at a range of population densities throughout larval development, kept them isolated during early adulthood, and then tested their sleep patterns. Our findings reveal that flies that had been isolated as larvae had more fragmented sleep than those that had been raised at higher population densities. This effect was more prominent in females than in males. Larval population density did not affect sleep in female flies that were mutant for amnesiac, which has been shown to be required for normal memory consolidation, adult sleep regulation, and brain development. In contrast, larval population density effects on sleep persisted in female flies lacking the olfactory receptor or83b, suggesting that olfactory signals are not required for the effects of larval population density on adult sleep. These findings show that population density during early development can alter sleep behavior in adulthood, suggesting that genetic and/or structural changes are induced by this developmental manipulation that persist through metamorphosis. PMID- 25116573 TI - The N-terminal transactivation domain of the glucocorticoid receptor mediates apoptosis of human small cell lung cancer cells. AB - Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis. These cancers are deficient in glucocorticoid receptor (GR) expression, and therefore, resistant to glucocorticoids. Overexpression of the GR both in vivo and in vitro leads to apoptotic cell death suggesting that loss of GR is favorable for cancer growth. Indeed, the GR promoter is silenced in SCLC cells by methylation. We now show that treatment of the SCLC cell line (DMS79) cells with the demethylating agent, 5-aza-2'-deoxycytidine (5-aza), results in significant endogenous re-expression of both GRalpha and the ligand-independent GR-P. The GR gene has a complex promoter region comprising nine alternative promoters, the proximal seven of which lie within a CpG island. The endogenous re-expression seen is attributed to the constitutive promoters 1B and 1C and 1J but predominantly 1F, which we show to be heavily methylated in SCLC cells. Flow cytometric analysis using the apoptotic marker, Annexin V, shows that this endogenous re-expression is sufficient to drive the SCLC cells to apoptosis. Apoptotic induction is specific to GR re-expression as cotreatment with 5-aza and the GR antagonist, RU486 prevented apoptosis. Of the three functional GR domains (the DNA binding domain, ligand binding domain, and transactivation domain), we identified that the transactivation domain is essential for apoptosis in SCLC. The discovery that endogenous re-expression of the GR in SCLC cells is sufficient to induce apoptotic cell death by reversing a cancer-driven DNA methylation effect may lead to the development of novel adjunct therapies. PMID- 25116572 TI - Dissociating Cortical Activity during Processing of Native and Non-Native Audiovisual Speech from Early to Late Infancy. AB - Initially, infants are capable of discriminating phonetic contrasts across the world's languages. Starting between seven and ten months of age, they gradually lose this ability through a process of perceptual narrowing. Although traditionally investigated with isolated speech sounds, such narrowing occurs in a variety of perceptual domains (e.g., faces, visual speech). Thus far, tracking the developmental trajectory of this tuning process has been focused primarily on auditory speech alone, and generally using isolated sounds. But infants learn from speech produced by people talking to them, meaning they learn from a complex audiovisual signal. Here, we use near-infrared spectroscopy to measure blood concentration changes in the bilateral temporal cortices of infants in three different age groups: 3-to-6 months, 7-to-10 months, and 11-to-14-months. Critically, all three groups of infants were tested with continuous audiovisual speech in both their native and another, unfamiliar language. We found that at each age range, infants showed different patterns of cortical activity in response to the native and non-native stimuli. Infants in the youngest group showed bilateral cortical activity that was greater overall in response to non native relative to native speech; the oldest group showed left lateralized activity in response to native relative to non-native speech. These results highlight perceptual tuning as a dynamic process that happens across modalities and at different levels of stimulus complexity. PMID- 25116574 TI - Effects of a multidomain lifestyle modification on cognitive function in older adults: an eighteen-month community-based cluster randomized controlled trial. AB - BACKGROUND: A healthy lifestyle may protect against cognitive decline. We examined outcomes in elderly individuals after 18 months of a five-group intervention program consisting of various modalities to prevent cognitive decline. METHODS: We conducted a cluster randomized controlled trial assessing 460 community-dwelling individuals aged 60 years and older in a geriatric community mental health center in Suwon, Republic of Korea, between 2008 and 2010. We developed an intervention program based on the principles of contingency management, which could be delivered by ordinary primary health workers. Group A (n = 81) received standard care services. Group B (n = 80) received bimonthly (once every 2 months) telephonic care management. Group C (n = 111) received monthly telephonic care management and educational materials similar to those in group B. Group D (n = 93) received bimonthly health worker-initiated visits and counseling. Group E (n = 94) received bimonthly health worker-initiated visits, counseling, and rewards for adherence to the program. RESULTS: The primary outcome was the change in Mini-Mental State Examination (MMSE) scores from baseline to the final follow-up visit at 18 months. Group E showed superior cognitive function to group A (adjusted coefficient beta = 0.99, p = 0.044), with participation in cognitive activities being the most important determining factor among several health behaviors (adjusted coefficient beta = 1.04, p < 0.01). CONCLUSIONS: Engaging in cognitive activities, in combination with positive health behaviors, may be most beneficial in preserving cognitive abilities in community-dwelling older adults. PMID- 25116575 TI - The desmoid tumour: local control after surgical treatment. AB - Desmoid tumours are uncommon non-malignant tumours that show a locally aggressive growth pattern and a high local recurrence rate after surgery. Approximately 10% of the desmoid tumours are associated with familial adenomatous polyposis (FAP). Variable natural history of the disease challenges treatment decision-making in the absence of prospective, randomised data. Association of this rare tumour to GIST is speculated and the tumorigenesis may share common steps. This study reviews given treatment and reports prognostic factors for local control and concurrent neoplasms in patients evaluated by a single soft tissue tumour group. Patients referred to the soft tissue tumour group at Helsinki University Central Hospital (HUCH) for a desmoid tumour (primary or recurred) during 1987-2007 and receiving surgical treatment with or without adjuvant treatment were included in this retrospective review. All locations and also patients with a FAP-associated tumour were included. Extra-abdominal location showed lower local control despite the fact that 27% of patients also received radiation therapy. One amputation was performed. Female sex and location in the rectus abdominis muscle predicted improved local control in multivariate analysis. In this review, the occurrence (14%) of concurrent neoplasms was higher than expected with unusual tumour types noted including two GISTs. In those patients in whom surgical treatment is chosen, adjuvant radiation therapy should also be considered in order to decrease morbidity from aggressive surgery aiming at R0 resection. Further studies are suggested to illuminate the biological association between the desmoid tumour and other neoplasms. PMID- 25116577 TI - Intracoronary injection of CD34-cells in chronic ischemic heart failure: 7 years follow-up of the DanCell study. AB - OBJECTIVES: Seven years ago, the DanCell study was carried out to test the hypothesis of improvement in left ventricular ejection fraction (LVEF) following repeated intracoronary injections of autologous bone marrow-derived stem cells (BMSCs) in patients suffering from chronic ischemic heart failure. In this post hoc analysis, the long-term effect of therapy is assessed. METHODS: 32 patients [mean age 61 (SD +/- 9), 81% males] with systolic dysfunction (LVEF 33 +/- 9%) received two repeated intracoronary infusions (4 months apart) of autologous BMSCs (1,533 +/- 765 * 10(6) BMSCs including 23 +/- 11 * 10(6) CD34(+) cells and 14 +/- 7 * 10(6) CD133(+) cells). Patients were followed for 7 years and deaths were recorded. RESULTS: During follow-up, 10 patients died (31%). In univariate regression analysis, the total number of BMSCs, CD34(+) cell count and CD133(+) cell count did not significantly correlate with survival (hazard ratio: 0.999, 95% CI: 0.998-1.000, p = 0.24; hazard ratio: 0.94, 95% CI: 0.88-1.01, p = 0.10, and hazard ratio: 0.96, 95% CI: 0.87-1.07, p = 0.47, respectively). After adjustment for baseline variables in multivariate regression analysis, the CD34(+) cell count was significantly associated with survival (hazard ratio: 0.90, 95% CI: 0.82-1.00, p = 0.04). CONCLUSIONS: Intracoronary injections of a high number of CD34(+) cells may have a beneficial effect on chronic ischemic heart failure in terms of long-term survival. PMID- 25116579 TI - The medicinal chemistry and drug development of novel antimalarials. PMID- 25116578 TI - Antimalarial bicyclic peroxides belonging to the G-factor family: mechanistic aspects of their formation and iron (II) induced reduction. AB - Artemisinin and its derivatives are peroxide-containing compounds targeting P. falciparum. We review here structural analogues of bicyclic peroxides belonging to the G factors family presenting antimalarial properties. They were synthesised under Mannich type conditions, followed by an autoxidation step resulting exclusively in the peroxide. As the electron transfer from haem or free iron to the peroxide is the first step in the mode of action of artemisinin-like compounds, the redox properties of some endoperoxides were studied by electrochemistry allowing the evaluation of the reduction standard potentials. The Fe(II) induced reduction was also investigated and the reactivity of the C centered radical intermediate formed was linked to the antimalarial activity. These bicyclic peroxides both with various hybrid molecules containing the endoperoxide framework were evaluated in vitro against Plasmodium falciparum. They exhibited moderate to good activities. PMID- 25116580 TI - 4-aminoquinoline based molecular hybrids as antimalarials: an overview. AB - In recent times, the novel concept of generating hybrid molecules by pharmacophoric hybridisation approach is fast becoming an alternative to other existing strategies of drug development. These hybrids also known as 'dual drugs' or 'double drugs' are especially found to be effective in overcoming drug resistance problems. Towards this end, a lot of effort has been put for generating 4-aminoquinoline based hybrid molecules as next generation antimalarial drugs effective in malarial chemotherapy. This short review deals about the recent advances carried in the field of 4-aminoquinoline based molecular hybrids as potential antimalarial agents. It also presents a brief and simplified story on the development of 4-aminoquinolines as a mainstay in malarial research programmes. PMID- 25116581 TI - Ferroquine as an oxidative shock antimalarial. AB - Over the course of the development of the antimalarial ferroquine, we have developed many ideas about its specific mechanism of action. Those ideas have enabled us to propose several experiments to control the validity of these hypotheses concerning differences between ferroquine and chloroquine and their respective mechanisms of action. We have now established an ultimate theory reconciling the hydrogen bond and the redox mechanisms hypotheses of ferroquine and fitting a wider range of published experimental results. PMID- 25116583 TI - Exploring prodrug approaches for albitiazolium and its analogues. AB - Choline analogues such as bis-thiazolium salts are thought to inhibit choline transport into Plasmodium-infected erythrocytes, thus preventing parasite PC biosynthesis, and also to interact with plasmodial haemoglobin degradation in the food vacuole. This new and multiple mode of action is a major asset of these new class of antimalarials, as they could help delay resistance development. We synthesized and designed various sets of analogues, notably prodrugs, since the oral bioavailability of bis-thiazolium salts is relatively low. The chemistry underlying this synthesis relies on inexpensive and readily available starting materials and is straightforward. This is essential since the ultimate objective is to obtain affordable and orally available drugs for uncomplicated malaria treatment. PMID- 25116584 TI - Antimalarial activities of indolones and derivatives. AB - The search for antimalarial compounds continues to be an area of intensive investigation in medicinal chemistry. This review presents the structural variations around the indolone-N-oxide core. From these pharmacomodulation studies, new antiplasmodial agents with various structures have emerged. Most of the molecules generated from reduced forms of the indolone scaffold have led to compounds with antiplasmodial properties. These results confirm the importance of the redox reversibility of the bioreducible N=C bond in these series to obtain antimalarial activities. PMID- 25116582 TI - 4(1H)-pyridone and 4(1H)-quinolone derivatives as antimalarials with erythrocytic, exoerythrocytic, and transmission blocking activities. AB - Infectious diseases are the second leading cause of deaths in the world with malaria being responsible for approximately the same amount of deaths as cancer in 2012. Despite the success in malaria prevention and control measures decreasing the disease mortality rate by 45% since 2000, the development of single-dose therapeutics with radical cure potential is required to completely eradicate this deadly condition. Targeting multiple stages of the malaria parasite is becoming a primary requirement for new candidates in antimalarial drug discovery and development. Recently, 4(1H)- pyridone, 4(1H)-quinolone, 1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have been shown to be antimalarials with blood stage activity, liver stage activity, and transmission blocking activity. Advancements in structure-activity relationship and structure-property relationship studies, biological evaluation in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H) quinolone chemotypes are discussed. PMID- 25116585 TI - New anti-malarial drugs: who cares? AB - Most of the people suffering malaria do not know how complex is that disease and how hard searchers are working to fight against it. Some of these people are dying from malaria while still efficient drug combinations should have save their lives. But these drugs were not available for them when needed, or the diagnosis was wrong, or the drugs were fake, or the doctor was untrained, or the patient had no money. Should this terrible reality preclude the need for continuous research to develop new antimalarial drugs? Should people working in laboratories located in non-endemic countries adapt their project to that reality? Malaria eradication, then elimination was announced and broadcasted in the late sixties, and later forgotten. From that failure due to chloroquine resistance and after decades of less arrogant work, billions of dollars are on the table again to claim this goal. There were bed nets, drugs, vaccine and communication as starters, let's hope people in endemic countries will be winners. PMID- 25116586 TI - Quantum chemistry guide to PTRMS studies of as-yet undetected products of the bromine-atom initiated oxidation of gaseous elemental mercury. AB - A series of BrHgY compounds (Y = NO2, ClO, BrO, HOO, etc.) are expected to be formed in the Br-initiated oxidation of Hg(0) to Hg(II) in the atmosphere. These BrHgY compounds have not yet been reported in any experiment. This article investigates the potential to use proton-transfer reaction mass spectrometry (PTRMS) to detect these atmospherically important species. We show that reaction of the standard PTRMS reagent (H3O(+)) with BrHgY leads to stable parent (M + 1) ions, BrHgYH(+), for most of these radicals, Y. Rate constants for the proton transfer reaction H3O(+) + BrHgY are computed using average dipole orientation theory. Calculations are also carried out on the commercially available compounds HgCl2, HgBr2, and HgI2 to enable tests of the present work. PMID- 25116589 TI - Electronic control of the protonation rates of Fe-Fe bonds. AB - Protonation at metal-metal bonds is of fundamental interest in the context of the function of the active sites of hydrogenases and nitrogenases. In diiron dithiolate complexes bearing carbonyl and electron-donating ligands, the metal metal bond is the highest occupied molecular orbital (HOMO) with a "bent" geometry. Here we show that the experimentally measured rates of protonation (kH) of this bond and the energy of the HOMO as measured by the oxidation potential of the complexes (E1/2(ox)) correlate in a linear free energy relationship: ln kH = ((F(c - betaE1/2(ox)))/(RT)), where c is a constant and beta is the dimensionless Bronsted coefficient. The value of beta of 0.68 is indicative of a strong dependence upon energy of the HOMO: measured rates of protonation vary over 6 orders of magnitude for a change in E1/2(ox) of ca. 0.55 V (ca. 11 orders of magnitude/V). This relationship allows prediction of protonation rates of systems that are either too fast to measure experimentally or that possess additional protonation sites. It is further suggested that the nature of the bridgehead in the dithiolate ligand can exert a stereoelectronic influence: bulky substituents destabilize the HOMO, thereby increasing the rate of protonation. PMID- 25116590 TI - Structural phase transitions of a layered organic-inorganic hybrid compound: tetra(cyclopentylammonium) decachlorotricadmate(II), [C5H9NH3]4Cd3Cl10. AB - A layered organic-inorganic hybrid compound, tetra(cyclopentylammonium) decachlorotricadmate(II) (1), in which the two-dimensional [Cd3Cl10](4-)n networks built up from three face-sharing CdCl6 octahedra are separated by cyclopentylammonium cation bilayers, has been discovered as a new phase transition material. It undergoes two successive structural phase transitions, at 197.3 and 321.6 K, which were confirmed by differential scanning calorimetry measurements, variable-temperature structural analyses, and dielectric measurements. The crystal structures of 1 determined at 93, 298, and 343 K are solved in P212121, Pbca, and Cmca, respectively. A precise analysis of the structural differences between these three structures reveals that the origin of the phase transition at 197.3 K is ascribed to the order-disorder transition of the cyclopentylammonium cations, while the phase transition at 321.6 K originates from the distortion of the two-dimensional [Cd3Cl10](4-)n network. PMID- 25116591 TI - Sharing the tracks to good tucker: identifying the benefits and challenges of implementing community food programs for Aboriginal communities in Victoria. AB - Food insecurity is a significant issue in the Victorian Aboriginal population, contributing to the health disparity and reduced life expectancy. Community food programs are a strategy used to minimise individual level food insecurity, with little evidence regarding their effectiveness for Aboriginal populations. The aim of this study was to explore the role of community food programs operating for Aboriginal people in Victoria and their perceived influence on food access and nutrition. Semistructured interviews were conducted with staff (n=23) from a purposive sample of 18 community food programs across Victoria. Interviews explored the programs' operation, key benefits to the community, challenges and recommendations for setting up a successful community food program. Results were analysed using a qualitative thematic approach and revealed three main themes regarding key factors for the success of community food programs: (1) community food programs for Aboriginal people should support access to safe, affordable, nutritious food in a socially and culturally acceptable environment; (2) a community development approach is essential for program sustainability; and (3) there is a need to build the capacity of community food programs as part of a strategy to ensure sustainability. Community food programs may be an effective initiative for reducing food insecurity in the Victorian Aboriginal population. PMID- 25116588 TI - Macrophage-specific NOX2 contributes to the development of lung emphysema through modulation of SIRT1/MMP-9 pathways. AB - Reactive oxygen species (ROS) participate in the pathogenesis of emphysema. Among ROS-producing enzymes, NOX NADPH oxidases are thought to be responsible for tissue injury associated with several lung pathologies. To determine whether NOX2 and/or NOX1 participate in the development of emphysema, their expression patterns were first studied by immunohistochemistry in the lungs of emphysematous patients. Subsequently, we investigated their contribution to elastase-induced emphysema using NOX2- and NOX1-deficient mice. In human lung, NOX2 was mainly detected in macrophages of control and emphysematous lungs, while NOX1 was expressed in alveolar epithelium and bronchial cells. We observed an elevated number of NOX2-positive cells in human emphysematous lungs, as well as increased NOX2 and NOX1 mRNA expression in mouse lungs following elastase exposure. Elastase-induced alveolar airspace enlargement and elastin degradation were prevented in NOX2-deficient mice, but not in NOX1-deficient mice. This protection was independent of inflammation and correlated with reduced ROS production. Concomitantly, an elevation of sirtuin 1 (SIRT1) level and a decrease of matrix metalloproteinase-9 (MMP-9) expression and activity were observed in alveolar macrophages and neutrophils. We addressed the specific role of macrophage restricted functional NOX2 in elastase-induced lung emphysema using Ncf1 mutant mice and Ncf1 macrophage rescue mice (Ncf1 mutant mice with transgenic expression of Ncf1 only in CD68-positive mononuclear phagocytes; the MN mouse). Compared to WT mice, the lack of functional NOX2 led to decreased elastase-induced ROS production and protected against emphysema. In contrast, ROS production was restored specifically in macrophages from Ncf1 rescue mice and contributes to emphysema. Taken together, our results demonstrate that NOX2 is involved in the pathogenesis of human emphysema and macrophage-specific NOX2 participates in elastase-induced emphysema through the involvement of SIRT1/MMP-9 pathways in mice. PMID- 25116593 TI - Imaging molecular adsorption and desorption dynamics on graphene using terahertz emission spectroscopy. AB - Being an atomically thin material, graphene is known to be extremely susceptible to its environment, including defects and phonons in the substrate on which it is placed as well as gas molecules that surround it. Thus, any device design using graphene has to take into consideration all surrounding components, and device performance needs to be evaluated in terms of environmental influence. However, no methods have been established to date to readily measure the density and distribution of external perturbations in a quantitative and non-destructive manner. Here, we present a rapid and non-contact method for visualizing the distribution of molecular adsorbates on graphene semi-quantitatively using terahertz time-domain spectroscopy and imaging. We found that the waveform of terahertz bursts emitted from graphene-coated InP sensitively changes with the type of atmospheric gas, laser irradiation time, and ultraviolet light illumination. The terahertz waveform change is explained through band structure modifications in the InP surface depletion layer due to the presence of localized electric dipoles induced by adsorbed oxygen. These results demonstrate that terahertz emission serves as a local probe for monitoring adsorption and desorption processes on graphene films and devices, suggesting a novel two dimensional sensor for detecting local chemical reactions. PMID- 25116594 TI - Optimization of ethyl ester production assisted by ultrasonic irradiation. AB - This study presents the optimization of the continuous flow potassium hydroxide catalyzed synthesis of ethyl ester from palm oil with ultrasonic assistance. The process was optimized by application of factorial design and response surface methodology. The independent variables considered were ethanol to oil molar ratio, catalyst concentration, reaction temperature and ultrasonic amplitude; and the response was ethyl ester yield. The results show that ethanol to oil molar ratio, catalyst concentration, and ultrasonic amplitude have positive effect on ethyl ester yield, whereas reaction temperature has negative influence on ethyl ester yield. Second-order models were developed to predict the responses analyzed as a function of these three variables, and the developed models predicts the results in the experimental ranges studied adequately. This study shows that ultrasonic irradiation improved the ethyl ester production process to achieve ethyl ester yields above 92%. PMID- 25116595 TI - Application of ultrasound for enhanced extraction of prebiotic oligosaccharides from selected fruits and vegetables. AB - Ultrasound assisted extraction (UAE) was used to extract oligosaccharides from selected fruits (blueberry, nectarine, raspberry, watermelon) and vegetables (garlic, Jerusalem artichoke, leek, scallion, spring garlic and white onion). The individual fractions of the oligosaccharides were analyzed: 1-kestose (GF2), nystose (GF3) and 1F-beta-fructofuranosylnystose (GF4) from the fructo oligosaccharides (FOS), and raffinose and stachyose from the raffinose family oligosaccharides (RFO). Extraction parameters including solvent concentration (35 85% v/v), extraction temperature (25-50 degrees C) and sonication time (5-15min) were examined using response surface methodology (RSM). Ethanol concentration of 63% v/v, temperature of 40 degrees C and extraction time of 10min gave maximal concentration of the extracted oligosaccharides. The experimental values under optimal conditions were consistent with the predicted values. UAE increased the concentration of extracted oligosaccharides in all fruits and vegetables from 2 to 4-fold compared to conventional extraction. The highest increase of total oligosaccharides extracted by UAE was detected in Jerusalem artichoke, 7.17+/ 0.348g/100gFW, compared to 1.62+/-0.094g/100gFW with conventional method. PMID- 25116592 TI - Clustering nuclear receptors in liver regeneration identifies candidate modulators of hepatocyte proliferation and hepatocarcinoma. AB - BACKGROUND & AIMS: Liver regeneration (LR) is a valuable model for studying mechanisms modulating hepatocyte proliferation. Nuclear receptors (NRs) are key players in the control of cellular functions, being ideal modulators of hepatic proliferation and carcinogenesis. METHODS & RESULTS: We used a previously validated RT-qPCR platform to profile modifications in the expression of all 49 members of the NR superfamily in mouse liver during LR. Twenty-nine NR transcripts were significantly modified in their expression during LR, including fatty acid (peroxisome proliferator-activated receptors, PPARs) and oxysterol (liver X receptors, Lxrs) sensors, circadian masters RevErbalpha and RevErbbeta, glucocorticoid receptor (Gr) and constitutive androxane receptor (Car). In order to detect the NRs that better characterize proliferative status vs. proliferating liver, we used the novel Random Forest (RF) analysis to selected a trio of down regulated NRs (thyroid receptor alpha, Tralpha; farsenoid X receptor beta, Fxrbeta; Ppardelta) as best discriminators of the proliferating status. To validate our approach, we further studied PPARdelta role in modulating hepatic proliferation. We first confirmed the suppression of PPARdelta both in LR and human hepatocellular carcinoma at protein level, and then demonstrated that PPARdelta agonist GW501516 reduces the proliferative potential of hepatoma cells. CONCLUSIONS: Our data suggest that NR transcriptome is modulated in proliferating liver and is a source of biomarkers and bona fide pharmacological targets for the management of liver disease affecting hepatocyte proliferation. PMID- 25116596 TI - Combining collagen and bioactive glasses for bone tissue engineering: a review. AB - Collagen (COL), the most abundant protein in mammals, offers a wide range of attractive properties for biomedical applications which are the result of its biocompatibility and high affinity to water. However, due to the relative low mechanical properties of COL its applications are still limited. To tackle this disadvantage of COL, especially in the field of bone tissue engineering, COL can be combined with bioactive inorganic materials in a variety of composite systems. One of such systems is the collagen-bioactive glass (COL-BG) composite family, which is the theme of this Review. BG fillers can increase compressive strength and stiffness of COL-based structures. This article reviews the relevant literature published in the last 15 years discussing the fabrication of a variety of COL-BG composites. In vitro cell studies have demonstrated the osteogenic, odontogenic, and angiogenic potential of these composite systems, which has been confirmed by stimulating specific biochemical indicators of relevant cells. Bony integration and connective tissue vessel formation have also been studied by implantation of the composites in vivo. Areas of future research in the field of COL-BG systems, based on current challenges, and gaps in knowledge are highlighted. PMID- 25116597 TI - Effect of oxygen, moisture and illumination on the stability and reliability of dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) OTFTs during operation and storage. AB - We report a systemic study of the stability of organic thin film transistors (OTFTs) both in storage and under operation. Apart from a thin polystyrene buffer layer spin-coated onto the gate dielectric, the constituent parts of the OTFTs were all prepared by vacuum evaporation. The OTFTs are based on the semiconducting small molecule dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) deposited onto the surface of a polystyrene-buffered in situ polymerized diacrylate gate insulator. Over a period of 9 months, no degradation of the hole mobility occurred in devices stored either in the dark in dry air or in uncontrolled air and normal laboratory fluorescent lighting conditions. In the latter case, rather than decreasing, the mobility actually increased almost 2 fold to 1.5 cm(2)/(V . s). The devices also showed good stability during repeat on/off cycles in the dark in dry air. Exposure to oxygen and light during the on/off cycles led to a positive shift of the transfer curves due to electron trapping when the DNTT was biased into depletion by the application of positive gate voltage. When operated in accumulation, negative gate voltage under the same conditions, the transfer curves were stable. When voltage cycling in moist air in the dark, the transfer curves shifted to negative voltages, thought to be due to the generation of hole traps either in the semiconductor or its interface with the dielectric layer. When subjected to gate bias stress in dry air in the dark for at least 144 h, the device characteristics remained stable. PMID- 25116598 TI - Small changes result in large differences: discovery of (-)-incrustoporin derivatives as novel antiviral and antifungal agents. AB - On the basis of the structure of natural product (-)-incrustoporin (1), a series of lactone compounds 4a-i and 5a-i were designed and synthesized from nitroolefin. The antiviral and antifungal activities of these compounds were evaluated in vitro and in vivo. The small changes between 4 and 5 at the 3,4 position result in large differences in bioactivities. Compounds 4 exhibited significantly higher antiviral activity against tobacco mosaic virus (TMV) than dehydro compounds 5. However, the antifungal activity of 4 is relatively lower than that of 5. Compounds 4a, 4c, and 4i with excellent in vivo anti-TMV activity emerged as new antiviral lead compounds. Compounds 5d-g showed superiority over the commercial fungicides chlorothalonil and carbendazim against Cercospora arachidicola Hor at 50 mg kg(-1). The present study provides fundamental support for the development and optimization of (-)-incrustoporin derivatives as potential inhibitors of plant virus and pathogenic fungi. PMID- 25116599 TI - Microfluidic device with integrated microfilter of conical-shaped holes for high efficiency and high purity capture of circulating tumor cells. AB - Capture of circulating tumor cells (CTCs) from peripheral blood of cancer patients has major implications for metastatic detection and therapy analyses. Here we demonstrated a microfluidic device for high efficiency and high purity capture of CTCs. The key novelty of this approach lies on the integration of a microfilter with conical-shaped holes and a micro-injector with cross-flow components for size dependent capture of tumor cells without significant retention of non-tumor cells. Under conditions of constant flow rate, tumor cells spiked into phosphate buffered saline could be recovered and then cultured for further analyses. When tumor cells were spiked in blood of healthy donors, they could also be recovered at high efficiency and high clearance efficiency of white blood cells. When the same device was used for clinical validation, CTCs could be detected in blood samples of cancer patients but not in that of healthy donors. Finally, the capture efficiency of tumor cells is cell-type dependent but the hole size of the filter should be more closely correlated to the nuclei size of the tumor cells. Together with the advantage of easy operation, low-cost and high potential of integration, this approach offers unprecedented opportunities for metastatic detection and cancer treatment monitoring. PMID- 25116600 TI - Fatty acid desaturation index in human plasma: comparison of different analytical methodologies for the evaluation of diet effects. AB - Stearoyl-CoA desaturase 1 (SCD1) plays a role in the development of obesity and related conditions, such as insulin resistance, and potentially also in neurological and heart diseases. The activity of SCD1 can be monitored using the desaturation index (DI), the ratio of product (16:1n-7 and 18:1n-9) to precursor (16:0 and 18:0) fatty acids. Here, different analytical strategies were applied to identify the method which best supports SCD1 biology. A novel effective approach was the use of the SCD1-independent fatty acid (16:1n-10) as a negative control. The first approach was based on a simple extraction followed by neutral loss triglyceride fatty acid analysis. The second approach was based on the saponification of triglycerides followed by fatty acid analysis (specific for the position of the double bond within monounsaturated fatty acids (MUFAs)). In addition to the analytical LC-MS assays, different matrices (plasma total triglyceride fraction and the very low-density lipoprotein (VLDL) fraction) were investigated to identify the best for studying changes in SCD1 activity. Samples from volunteers on a high-carbohydrate diet were analyzed. Both ultra HPLC (UHPLC)-MS-based assays showed acceptable accuracies (75-125% of nominal) and precisions (<20%) for the analysis of DI-specific fatty acids in VLDL and plasma. The most specific assay for the analysis of the liver SCD activity was then validated for specificity and selectivity, intra- and interday accuracy and precision, matrix effects, dilution effects, and analyte stability. After 3 days of high-carbohydrate diet, only the specific fatty acids in human plasma VLDL showed a significant increase in DI and associated SCD1 activity. PMID- 25116601 TI - Size-exclusion chromatography-from high-performance to ultra-performance. AB - Size-exclusion chromatography (SEC) enables measurement of the average molecular weights and molecular-weight distributions of polymers. Because these characteristics may, in turn, be correlated with important performance characteristics of plastics, SEC is an essential analytical technique for characterization of macromolecules. Although SEC is one of the oldest instrumental chromatographic techniques, it is still under continuous development, as a result of the great demand for increased resolution and faster analysis in SEC. Ultra-high-pressure size-exclusion chromatography (UHPSEC) was recently introduced to satisfy the growing demands of analytical chemists. Using instrumentation capable of generating very high pressures and columns packed with small particles, this technique enables greater separation efficiency and faster analysis than are achieved with conventional SEC. UHPSEC is especially advantageous for high-resolution analysis of oligomers, for very rapid polymer separations, and as a second dimension in comprehensive two-dimensional liquid chromatography of polymers. In this paper we discuss the benefits of UHPSEC for separation of macromolecules, with examples from the literature. PMID- 25116602 TI - Analysis of N-acylhomoserine lactone dynamics in continuous cultures of Pseudomonas putida IsoF by use of ELISA and UHPLC/qTOF-MS-derived measurements and mathematical models. AB - In this interdisciplinary approach, the dynamics of production and degradation of the quorum sensing signal 3-oxo-decanoylhomoserine lactone were studied for continuous cultures of Pseudomonas putida IsoF. The signal concentrations were quantified over time by use of monoclonal antibodies and ELISA. The results were verified by use of ultra-high-performance liquid chromatography. By use of a mathematical model we derived quantitative values for non-induced and induced signal production rate per cell. It is worthy of note that we found rather constant values for different rates of dilution in the chemostat, and the values seemed close to those reported for batch cultures. Thus, the quorum-sensing system in P. putida IsoF is remarkably stable under different environmental conditions. In all chemostat experiments, the signal concentration decreased strongly after a peak, because emerging lactonase activity led to a lower concentration under steady-state conditions. This lactonase activity probably is quorum sensing-regulated. The potential ecological implication of such unique regulation is discussed. PMID- 25116603 TI - Separation and quantification of monoclonal-antibody aggregates by hollow-fiber flow field-flow fractionation. AB - Hollow-fiber-flow field-flow fractionation (HF5) separates protein molecules on the basis of the difference in the diffusion coefficient, and can evaluate the aggregation ratio of proteins. However, HF5 is still a minor technique because information on the separation conditions is limited. We examined in detail the effect of different settings, including the main-flow rate, the cross-flow rate, the focus point, the injection amount, and the ionic strength of the mobile phase, on fractographic characteristics. On the basis of the results, we proposed optimized conditions of the HF5 method for quantification of monoclonal antibody in sample solutions. The HF5 method was qualified regarding the precision, accuracy, linearity of the main peak, and quantitation limit. In addition, the HF5 method was applied to non-heated Mab A and heat-induced-antibody-aggregate containing samples to evaluate the aggregation ratio and the distribution extent. The separation performance was comparable with or better than that of conventional methods including analytical ultracentrifugation-sedimentation velocity and asymmetric-flow field-flow fractionation. PMID- 25116604 TI - Characterization of poly(2-vinylpyridine)-block-poly(methyl methacrylate) copolymers and blends of their homopolymers by liquid chromatography at critical conditions. AB - Poly(2-vinylpyridine)s (P2VPs) are important polymers with extensive applications in modern day material science. P2VP is an exceptional case for liquid chromatography because of certain polar interactions with most of the stationary phases. In the present study, we established the critical adsorption point (CAP) of P2VP for the first time. The effectiveness of the method is demonstrated by analyses of blends and block copolymers of P2VP and PMMA. The CAP of PMMA is established for determination of molar mass of P2VP component of above mentioned blends and block copolymers. The methods successfully demonstrate the separation of both types of homopolymers from the rest of the samples in conjunction with the determination of molar mass distribution of noncritical block or component. PMID- 25116606 TI - Emulsion-templated silica nanocapsules formed using bio-inspired silicification. AB - A novel, bio-inspired templating platform technology is reported for the synthesis of biocompatible oil-core silica-shell nanocapsules with tunable shell thickness by utilizing a designed bifunctional peptide. Furthermore, facile encapsulation of an active molecule and its sustained release are demonstrated. PMID- 25116607 TI - Remembering Obaid - one year later. PMID- 25116605 TI - Effects of initial boost with TGF-beta 1 and grade of intervertebral disc degeneration on 3D culture of human annulus fibrosus cells. AB - BACKGROUND: Three-dimensional (3D) culture in porous biomaterials as well as stimulation with growth factors are known to be supportive for intervertebral disc cell differentiation and tissue formation. Unless sophisticated releasing systems are used, however, effective concentrations of growth factors are maintained only for a very limited amount of time in in vivo applications. Therefore, we investigated, if an initial boost with transforming growth factor beta 1 (TGF-beta 1) is capable to induce a lasting effect of superior cartilaginous differentiation in slightly and severely degenerated human annulus fibrosus (AF) cells. METHODS: Human AF tissue was harvested during surgical treatment of six adult patients with lumbar spinal diseases. Grading of disc degeneration was performed with magnet resonance imaging. AF cells were isolated and expanded in monolayer culture and rearranged three-dimensionally in a porous biomaterial consisting of stepwise absorbable poly-glycolic acid and poly-(lactic co-glycolic) acid and a supportive fine net of non-absorbable polyvinylidene fluoride. An initial boost of TGF-beta 1 or TGF-beta 1 and hyaluronan was applied and compared with controls. Matrix formation was assessed at days 7 and 21 by (1) histological staining of the typical extracellular matrix molecules proteoglycan and type I and type II collagens and by (2) real-time gene expression analysis of aggrecan, decorin, biglycan, type I, II, III, and X collagens as well as of catabolic matrix metalloproteinases MMP-2 and MMP-13. RESULTS: An initial boost with TGF-beta 1 or TGF-beta 1 and hyaluronan did not enhance the expression of characteristic AF matrix molecules in our 3D culture system. AF cells showed high viability in the progressively degrading biomaterial. Stratification by grade of intervertebral disc degeneration showed that AF cells from both, slightly degenerated, or severely degenerated tissue are capable of significant up regulations of characteristic matrix molecules in 3D culture. AF cells from severely degenerated tissue, however, displayed significantly lower up regulations in some matrix molecules such as aggrecan. CONCLUSIONS: We failed to show a supportive effect of an initial boost with TGF-beta 1 in our 3D culture system. This underlines the need for further investigations on growth factor releasing systems. PMID- 25116608 TI - Recalling Obaid. PMID- 25116609 TI - Remembering Obaid Siddiqi, a pioneer in the study of temperature-sensitive paralytic mutants in Drosophila. AB - Although Obaid Siddiqi's major research focus in neurogenetics was on chemosensation and olfaction in Drosophila, he made seminal contributions to the study of temperature-sensitive paralytic mutants that paved the way for research that we and many other investigators have continued to pursue. Here we recount Siddiqi's investigation and the impact it had on our own studies especially at a formative stage of our careers. We acknowledge our debt to Obaid Siddiqi and remember him fondly as an inspired and inspiring scientist, mentor, role model and human being. PMID- 25116610 TI - Molecular determinants of odorant receptor function in insects. AB - The olfactory system of Drosophila melanogaster provides a powerful model to study molecular and cellular mechanisms underlying function of a sensory system. In the 1970s Siddiqi and colleagues pioneered the application of genetics to olfactory research and isolated several mutant Drosophila with odorant-specific defects in olfactory behaviour, suggesting that odorants are detected differentially by the olfactory system. Since then basic principles of olfactory system function and development have emerged using Drosophila as a model. Nearly four decades later we can add computational methods to further our understanding of how specific odorants are detected by receptors. Using a comparative approach we identify two categories of short amino acid sequence motifs: ones that are conserved family-wide predominantly in the C-terminal half of most receptors, and ones that are present in receptors that detect a specific odorant, 4 methylphenol, found predominantly in the N-terminal half. The odorant-specific sequence motifs are predictors of phenol detection in Anopheles gambiae and other insects, suggesting they are likely to participate in odorant binding. Conversely, the family-wide motifs are expected to participate in shared functions across all receptors and a mutation in the most conserved motif leads to a reduction in odor response. These findings lay a foundation for investigating functional domains within odorant receptors that can lead to a molecular understanding of odor detection. PMID- 25116611 TI - A map of taste neuron projections in the Drosophila CNS. AB - We provide a map of the projections of taste neurons in the CNS of Drosophila. Using a collection of 67 GAL4 drivers representing the entire repertoire of Gr taste receptors, we systematically map the projections of neurons expressing these drivers in the thoracico-abdominal ganglion and the suboesophageal ganglion (SOG). We define 9 categories of projections in the thoracico-abdominal ganglia and 10 categories in the SOG. The projection patterns are modular, and can be interpreted as combinations of discrete pattern elements. The elements can be interpreted in terms of the taste organ from which the projections originate, the structures from which they originate, and the quality of taste information that they represent. The extensive diversity in projection patterns provides an anatomical basis for functional diversity in responses elicited by different taste stimuli. PMID- 25116612 TI - Serotonergic neurons of the Drosophila air-puff-stimulated flight circuit. AB - Monoaminergic modulation of insect flight is well documented. Recently, we demonstrated that synaptic activity is required in serotonergic neurons for Drosophila flight. This requirement is during early pupal development, when the flight circuit is formed, as well as in adults. Using a Ca2+-activity-based GFP reporter, here we show that serotonergic neurons in both prothoracic and mesothoracic segments are activated upon air-puff-stimulated flight. Moreover ectopic activation of the entire serotonergic system by TrpA1, a heat activated cation channel, induces flight, even in the absence of an air-puff stimulus. PMID- 25116613 TI - Ultradian rhythm unmasked in the Pdf clock mutant of Drosophila. AB - A diverse range of organisms shows physiological and behavioural rhythms with various periods. Extensive studies have been performed to elucidate the molecular mechanisms of circadian rhythms with an approximately 24 h period in both Drosophila and mammals, while less attention has been paid to ultradian rhythms with shorter periods. We used a video-tracking method to monitor the movement of single flies, and clear ultradian rhythms were detected in the locomotor behaviour of wild type and clock mutant flies kept under constant dark conditions. In particular, the Pigment-dispersing factor mutant (Pdf 01) demonstrated a precise and robust ultradian rhythmicity, which was not temperature compensated. Our results suggest that Drosophila has an endogenous ultradian oscillator that is masked by circadian rhythmic behaviours. PMID- 25116614 TI - Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster. AB - Groundbreaking work by Obaid Siddiqi has contributed to the powerful genetic toolkit that is now available for studying the nervous system of Drosophila. Studies carried out in this powerful neurogenetic model system during the last decade now provide insight into the molecular mechanisms that operate in neural stem cells during normal brain development and during abnormal brain tumorigenesis. These studies also provide strong support for the notion that conserved molecular genetic programs act in brain development and disease in insects and mammals including humans. PMID- 25116615 TI - Continuous evolution of laboratory strains of bacteria and yeast. PMID- 25116616 TI - Gender based disruptive selection maintains body size polymorphism in Drosophila melanogaster. AB - Darwinian fitness in holometabolous insects like the fruit fly Drosophila melanogaster is reported to be positively correlated with body size. If large individuals in a population have higher fitness, then one would expect directional selection to operate leading to uniformly large individuals. However, size polymorphism persists in nature and needs further probing. We assessed the effect of body size on some of the fitness and fitness-related traits in replicate populations of genotypically large, genotypically small and phenotypically small D. melanogaster flies. In this study, the time taken to attain reproductive maturity and copulation duration were independent of fly size. Fecundity and longevity of large females were significantly higher when they partnered genotypically small males than when they were with genotypically larger or phenotypically small males. The increased female longevity when in association with genotypically small males was not due to selective early death of males that would release the female partner from presumed cost of persistent courtship. On the contrary, the genotypically as well as phenotypically small males had significantly higher longevity than large males. The virility of the genotypically small males was not significantly different from that of genotypically large males. Our results clearly show that selection on body size operates in the opposite direction (disruptive selection) for the two genders, thus explaining the persistence of size polymorphisms in the holometabolous insect, Drosophila melanogaster. PMID- 25116617 TI - 2'-O-methyl nucleotide modified DNA substrates influence the cleavage efficiencies of BamHI and BglII. AB - Induction of endonucleolytic DNA cleavage is an essential event that links the initiating stimuli to the final effects of cells. The cleavage efficiency and thus the final yield could be affected by many factors, including structures of DNA substrates, composite structures of enzymes-substrates or enzymes-nucleic analogs and so on. However, it is not clear whether a nucleotide derivative substituted in DNA substrates can influence the efficiency of enzymatic cleavage. To investigate the effect of sugar pucker conformation on DNA-protein interactions, we used 2'-O-methyl modified nucleotides (OMeN) to modify DNA substrates of isocaudemers BamHI and BglII in this study, and used FRET assay as an efficient method for analysis of enzyme cleavage. Experimental results demonstrated that OMeN-substituted recognition sequences influenced the cleavage rates significantly in a position-dependent manner. OMeN substitutions can reduce the cleavage as expected. Surprisingly, OMeN substitutions can also enhance the cleavage rates. The kinetics parameters of Vmax and Km have been obtained by fitting the Michaelis-Menten kinetic equation. These 2'- OMe nucleotides could behave as a regulatory element to modulate the enzymatic activity in vitro, and this property could enrich our understanding about the endonuclease cleavage mechanism and enhance our ability to regulate the enzymatic cleavage efficiency for applications in synthetic biology. PMID- 25116619 TI - Limnology and cyanobacterial diversity of high altitude lakes of Lahaul-Spiti in Himachal Pradesh, India. AB - Limnological data of four high altitude lakes from the cold desert region of Himachal Pradesh, India, has been correlated with cyanobacterial diversity. Physico-chemical characteristics and nutrient contents of the studied lakes revealed that Sissu Lake is mesotrophic while Chandra Tal, Suraj Tal and Deepak Tal are ultra-oligotrophic. Based on morphology and 16S rRNA gene sequence, a total of 20 cyanobacterial species belonging to 11 genera were identified. Canonical correspondence analysis distinguished three groups of species with respect to their occurrence and nutrient/physical environment demand. The first group, which included Nostoc linckia, N. punctiforme, Nodularia sphaerocarpa, Geitlerinema acutissimum, Limnothrix redekii, Planktothrix agardhii and Plank. clathrata, was characteristic of water with high nutrient content and high temperature. The second group, including Gloeocapsopsis pleurocapsoides, Leptolyngbya antarctica, L. frigida, Pseudanabaena frigida and N. spongiaeforme, occurred in oligotrophic water with high pH and low temperature. The distribution of third group of Cyanobium parvum, Synechocystis pevalekii, L. benthonica, L. foveolarum, L. lurida, L. valderiana, Phormidium autumnale and P. chalybeum could not be associated with a particular environmental condition because of their presence in all sampling sites. PMID- 25116618 TI - Avoiding acidic region streaking in two-dimensional gel electrophoresis: case study with two bacterial whole cell protein extracts. AB - Acidic region streaking (ARS) is one of the lacunae in two-dimensional gel electrophoresis (2DE) of bacterial proteome. This streaking is primarily caused by nucleic acid (NuA) contamination and poses major problem in the downstream processes like image analysis and protein identification. Although cleanup and nuclease digestion are practiced as remedial options, these strategies may incur loss in protein recovery and perform incomplete removal of NuA. As a result, ARS has remained a common observation across publications, including the recent ones. In this work, we demonstrate how ultrasound wave can be used to shear NuA in plain ice-cooled water, facilitating the elimination of ARS in the 2DE gels without the need for any additional sample cleanup tasks. In combination with a suitable buffer recipe, IEF program and frequent paper-wick changing approach, we are able to reproducibly demonstrate the production of clean 2DE gels with improved protein recovery and negligible or no ARS. We illustrate our procedure using whole cell protein extracts from two diverse organisms, Escherichia coli and Mycobacterium smegmatis. Our designed protocols are straightforward and expected to provide good 2DE gels without ARS, with comparable times and significantly lower cost. PMID- 25116620 TI - Conserved C-terminal nascent peptide binding domain of HYPK facilitates its chaperone-like activity. AB - Human HYPK (Huntingtin Yeast-two-hybrid Protein K) is an intrinsically unstructured chaperone-like protein with no sequence homology to known chaperones. HYPK is also known to be a part of ribosome-associated protein complex and present in polysomes. The objective of the present study was to investigate the evolutionary influence on HYPK primary structure and its impact on the protein's function. Amino acid sequence analysis revealed 105 orthologs of human HYPK from plants, lower invertebrates to mammals. C-terminal part of HYPK was found to be particularly conserved and to contain nascent polypeptide associated alpha subunit (NPAA) domain. This region experiences highest selection pressure, signifying its importance in the structural and functional evolution. NPAA domain of human HYPK has unique amino acid composition preferring glutamic acid and happens to be more stable from a conformational point of view having higher content of a-helices than the rest. Cell biology studies indicate that overexpressed C-terminal human HYPK can interact with nascent proteins, co localizes with huntingtin, increases cell viability and decreases caspase activities in Huntington's disease (HD) cell culture model. This domain is found to be required for the chaperone-like activity of HYPK in vivo. Our study suggested that by virtue of its flexibility and nascent peptide binding activity, HYPK may play an important role in assisting protein (re)folding. PMID- 25116621 TI - Skin anti-photoaging properties of ginsenoside Rh2 epimers in UV-B-irradiated human keratinocyte cells. AB - Ginseng, one of the most widely used herbal medicines, has a wide range of therapeutic and pharmacological applications. Ginsenosides are the major bioactive ingredients of ginseng, which are responsible for various pharmacological activities of ginseng. Ginsenoside Rh2, known as an antitumour ginsenoside, exists as two different stereoisomeric forms, 20(S)-ginsenoside Rh2 [20(S)-Rh2] and 20(R)-ginsenoside Rh2 [20(R)-Rh2]. This work aimed to assess and compare skin anti-photoaging activities of 20(S)-Rh2 and 20(R)-Rh2 in UV-B irradiated HaCat cells. 20(S)-Rh2, but not 20(R)-Rh2, was able to suppress UV-B induced ROS production in HaCat cells. Both stereoisomeric forms could not modulate cellular survival and NO level in UV-B-irradiated HaCat cells. Both 20(S)-Rh2 and 20(R)-Rh2 exhibited suppressive effects on UV-B-induced MMP-2 activity and expression in HaCat cells. In brief, the two stereoisomers of ginsenoside Rh2, 20(S)-Rh2 and 20(R)-Rh2, possess skin anti-photoaging effects but possibly in different fashions. PMID- 25116622 TI - Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells. AB - Autophagy and apoptosis function as important early cellular defense mechanisms in infections and other diseases. The outcome of an infection is determined by a complex interplay between the pathogenic microorganism and these intracellular pathways. To better understand the cytopathogenicity of Herpes simplex virus types 1 and 2 (HSV-1 and - 2), we studied the effect of these viruses on the autophagic and apoptotic processes in the SIRC corneal cell line. Infection with the KOS strain of HSV-1 and a wild-type strain of HSV-2 enhanced autophagosome formation, triggered cytoplasmic acidification, increased LC3B lipidation and elevated the ratio of apoptotic cells. The autophagy inhibitor bafilomycin A1 triggered a significant increase in the apoptotic responses of HSV-1 and HSV-2 infected cells. Thus, both HSV types affect autophagy and apoptosis in a coordinated fashion, and autophagy plays cytoprotective role in HSV-infected cells via antagonizing apoptosis. Together these data implicate autophagy in the pathogenic mechanism of herpetic keratitis. PMID- 25116623 TI - Platelet-derived growth factor mediates interleukin-13-induced collagen I production in mouse airway fibroblasts. AB - Interleukin-13 (IL-13) is associated with the production of collagen in airway remodelling of asthma. Yet, the molecular mechanisms underlying IL-13 induction of collagen remain unclear; the aim of this study is to address this issue. IL-13 dose- and time-dependently-induced collagen I production in primary cultured airway fibroblasts; this was accompanied with the STAT6 phosphorylation, and pre treatment of cells with JAK inhibitor suppressed IL-13- induced collagen I production. Further study indicated that IL-13 stimulated JAK/STAT6-dependent PDGF production and subsequent ERK1/2 MAPK activation in airway fibroblasts, and the presence of either PDGF receptor blocker or MEK inhibitor partially suppressed IL-13-induced collagen I production. Taken together, our study suggests that activation of JAK/STAT6 signal pathway and subsequent PDGF generation and resultant ERK1/2 MAPK activation mediated IL-13-induced collagen I production in airway fibroblasts. PMID- 25116624 TI - Determining sensitive stages for learning to detect predators in larval bronzed frogs: importance of alarm cues in learning. AB - Successful survival and reproduction of prey organisms depend on their ability to detect their potential predators accurately and respond effectively with suitable defences. Predator detection can be innate or can be acquired through learning.We studied prey-predator interactions in the larval bronzed frogs (Sylvirana temporalis), which have the innate ability to detect certain predators. We conducted a series of experiments to determine if the larval S. temporalis rely solely on innate predator detection mechanisms or can also learn to use more specific cues such as conspecific alarm cues for the purpose. The results of our study clearly indicate that larval S. temporalis use both innate and learned mechanisms for predator detection. Predator-naive tadpoles could detect kairomones alone as a potential threat and responded by reducing activity, suggesting an innate predator detection mechanism. Surprisingly, predator-naive tadpoles failed to detect conspecific alarm cues as a potential threat, but learned to do so through experience. After acquiring the ability to detect conspecific alarm cues, they could associate novel predator cues with conspecific alarm cues. Further, post feeding stages of larval S. temporalis are sensitive for learning to detect conspecific alarm cues to label novel predators. PMID- 25116625 TI - DNA barcoding of a new record of epi-endophytic green algae Ulvella leptochaete (Ulvellaceae, Chlorophyta) in India. AB - Epi-endophytic green algae comprise one of the most diverse and phylogenetically primitive groups of green algae and are considered to be ubiquitous in the world's oceans; however, no reports of these algae exist from India. Here we report the serendipitous discovery of Ulvella growing on intertidal green algae Cladophora glomerata and benthic red algae Laurencia obtusa collected from India. DNA barcodes at nuclear ribosomal DNA Internal Transcriber Spacer (nrDNA ITS) 1 and 2 regions for Indian isolates from the west and east coasts have been generated for the first time. Based on morphology and DNA barcoding, isolates were identified as Ulvella leptochaete. Phylogenetic reconstruction of concatenated dataset using Maximum Likelihood method differentiated Indian isolates from other accessions of this alga available in Genbank, albeit with low bootstrap support. Monophyly of Ulvella leptochaete was obvious in both of our phylogenetic analyses. With this first report of epi-endophytic algae from Indian territorial waters, the dire need to catalogue its cryptic diversity is highlighted and avenues of future research are discussed. PMID- 25116626 TI - Lantana camara L. (Verbenaceae) invasion along streams in a heterogeneous landscape. AB - Streams are periodically disturbed due to flooding, act as edges between habitats and also facilitate the dispersal of propagules, thus being potentially more vulnerable to invasions than adjoining regions. We used a landscape-wide transect based sampling strategy and a mixed effects modelling approach to understand the effects of distance from stream, a rainfall gradient, light availability and fire history on the distribution of the invasive shrub Lantana camara L.(lantana) in the tropical dry forests of Mudumalai in southern India. The area occupied by lantana thickets and lantana stem abundance were both found to be highest closest to streams across this landscape with a rainfall gradient. There was no advantage in terms of increased abundance or area occupied by lantana when it grew closer to streams in drier areas as compared to moister areas. On an average, the area covered by lantana increased with increasing annual rainfall. Areas that experienced greater number of fires during 1989-2010 had lower lantana stem abundance irrespective of distance from streams. In this landscape, total light availability did not affect lantana abundance. Understanding the spatially variable environmental factors in a heterogeneous landscape influencing the distribution of lantana would aid in making informed management decisions at this scale. PMID- 25116628 TI - Which dimensions of disability does the HIV Disability Questionnaire (HDQ) measure? A factor analysis. AB - PURPOSE: To assess the dimensions of disability measured by the HIV Disability Questionnaire (HDQ), a newly developed 72-item self-administered questionnaire that describes the presence, severity and episodic nature of disability experienced by people living with HIV. METHODS: We recruited adults living with HIV from hospital clinics, AIDS service organizations and a specialty hospital and administered the HDQ followed by a demographic questionnaire. We conducted an exploratory factor analysis using disability severity scores to determine the domains of disability in the HDQ. We used the following steps: (a) ensured correlations between items were >0.30 and <0.80; (b) conducted a principal components analysis to extract factors; (c) used the Scree Test and eigenvalue threshold >1.5 to determine the number of factors to retain; and d) used oblique rotation to simplify the factor loading matrix. We assigned items to factors based on factor loadings of >0.30. RESULTS: Of the 361 participants, 80% were men and 77% reported living with at least two concurrent health conditions in addition to HIV. The exploratory factor analysis suggested retaining six factors. Items related to symptoms and impairments loaded on three factors (physical [20 items], cognitive [3 items], and mental and emotional health [11 items]) and items related to worrying about the future, daily activities, and personal relationships loaded on three additional factors (uncertainty [14 items], difficulties with day-to-day activities [9 items], social inclusion [12 items]). CONCLUSIONS: The HDQ has six domains: physical symptoms and impairments; cognitive symptoms and impairments; mental and emotional health symptoms and impairments; uncertainty; difficulties with day-to-day activities and challenges to social inclusion. These domains establish the scoring structure for the dimensions of disability measured by the HDQ. Implications for Rehabilitation As individuals live longer and age with HIV, they may be living with the health related consequences of HIV and concurrent health conditions, a concept that may be termed disability. Measuring disability is important to understand the impact of HIV and its comorbidities. The HIV Disability Questionnaire (HDQ) is a self administered questionnaire developed to describe the presence, severity and episodic nature of disability experienced by people living with HIV. The HDQ is comprised of six domains of disability including: physical symptoms and impairments (20 items); cognitive symptoms and impairments (3 items); mental and emotional health symptoms and impairments (11 items); uncertainty (14 items); difficulties with day-to-day activities (9 items) and challenges to social inclusion (12 items). These domains represent the dimensions of disability measured by the HDQ. The HDQ is the first known HIV-specific disability measure for adults living with HIV. The HDQ may be used by clinicians and researchers to assess disability experienced by adults living with HIV. PMID- 25116629 TI - Stabilizing characteristics of rotator cuff muscles: a systematic review. AB - PURPOSE: To systematically review the evidence in support of the purported function of the rotator cuff muscles as dynamic stabilizers of the glenohumeral joint. METHODS: Electronic searches were conducted using AMED, CINAHL, Medline and SPORT Discus. Studies were required to include at least one characteristic of a stabilizer muscle. Quality analysis was completed by two assessors independently. Data were extracted for four main characteristics of stabilizer muscles: (1) moment arm length, (2) onset of muscle activity, (3) joint stiffness as measured by contribution of muscle activity to prevent joint translation, (4) co-contraction as demonstrated by electromyography muscle activity and co activation ratio. RESULTS: Twenty of the 1726 identified studies were selected for the review. Rotator cuff muscles can limit joint translation (five studies) and contribute to joint stiffness (one study), possess shorter moment arms in some movements (three studies), but show limited evidence for stabilizing characteristics of early onset (seven studies) and co-contraction (seven studies). CONCLUSION: The rotator cuff muscles exhibited some stabilization characteristics but not all. On the basis of our current low to moderate quality evidence, the most likely, but as yet unverified, stabilization role for the rotator cuff muscles appears to be limiting of translation in a direction specific manner. IMPLICATIONS FOR REHABILITATION: Diagnostic tests currently used are based largely on the assumption that the muscles of the rotator cuff can be individually recruited as prime movers. Our findings demonstrate the need for more research into the proposed stabilizing mechanisms of the rotator cuff muscles to increase diagnostic accuracy and more targeted shoulder rehabilitation programs. It may be that the rotator cuff muscles have a role in limiting glenohumeral joint translation which is not reflected in the current diagnostic tests and rehabilitation protocols. Further research is required to establish this stabilizing characteristic in living subjects. Knowledge of the contribution of rotator cuff muscle activation in limiting joint translation may be an important aspect in properly assessing and quantifying the proposed function of the rotator cuff muscles as dynamic stabilizers of the shoulder joint. PMID- 25116627 TI - Does malaria epidemiology project Cameroon as 'Africa in miniature'? AB - Cameroon, a west-central African country with a ~ 20 million population, is commonly regarded as 'Africa in miniature' due to the extensive biological and cultural diversities of whole Africa being present in a single-country setting. This country is inhabited by ancestral human lineages in unique eco-climatic conditions and diverse topography. Over 90 percent Cameroonians are at risk of malaria infection, and ~ 41 percent have at least one episode of malaria each year. Historically, the rate of malaria infection in Cameroon has fluctuated over the years; the number of cases was about 2 million in 2010 and 2011. The Cameroonian malaria control programme faces an uphill task due to high prevalence of multidrug-resistant parasites and insecticide-resistant malaria vectors. Above all, continued human migration from the rural to urban areas as well as population exchange with adjoining countries, high rate of ecological instabilities caused by deforestation, poor housing, lack of proper sanitation and drainage system might have resulted in the recent increase in incidences of malaria and other vector-borne diseases in Cameroon. The available data on eco environmental variability and intricate malaria epidemiology in Cameroon reflect the situation in the whole of Africa, and warrant the need for in-depth study by using modern surveillance tools for meaningful basic understanding of the malaria triangle (host-parasite-vector-environment). PMID- 25116632 TI - Design, synthesis and aphicidal activity of N-terminal modified insect kinin analogs. AB - The insect kinins are a class of multifunctional insect neuropeptides present in a diverse variety of insects. Insect kinin analogs showed multiple bioactivities, especially, the aphicidal activity. To find a biostable and bioactive insecticide candidate with simplified structure, a series of N-terminal modified insect kinin analogs was designed and synthesized based on the lead compound [Aib]-Phe-Phe [Aib]-Trp-Gly-NH2. Their aphicidal activity against the soybean aphid Aphis glycines was evaluated. The results showed that all the analogs maintained the aphicidal activity. In particular, the aphicidal activity of the pentapeptide analog X Phe-Phe-[Aib]-Trp-Gly-NH2 (LC50=0.045mmol/L) was similar to the lead compound (LC50=0.048mmol/L). This indicated that the N-terminal protective group may not play an important role in the activity and the analogs structure could be simplified to pentapeptide analogs while retaining good aphicidal activity. The core pentapeptide analog X can be used as the lead compound for further chemical modifications to discover potential insecticides. PMID- 25116630 TI - Terminal sialic acids on CD44 N-glycans can block hyaluronan binding by forming competing intramolecular contacts with arginine sidechains. AB - Specific sugar residues and their linkages form the basis of molecular recognition for interactions of glycoproteins with other biomolecules. Seemingly small changes, like the addition of a single monosaccharide in the covalently attached glycan component of glycoproteins, can greatly affect these interactions. For instance, the sialic acid capping of glycans affects protein ligand binding involved in cell-cell and cell-matrix interactions. CD44 is a single-pass transmembrane glycoprotein whose binding with its carbohydrate ligand hyaluronan (HA), an extracellular matrix component, mediates processes such as leukocyte homing, cell adhesion, and tumor metastasis. This binding is highly regulated by glycosylation of the N-terminal extracellular hyaluronan-binding domain (HABD); specifically, sialic acid capped N-glycans of HABD inhibit ligand binding. However, the molecular mechanism behind this sialic acid mediated regulation has remained unknown. Two of the five N-glycosyation sites of HABD have been previously identified as having the greatest inhibitory effect on HA binding, but only if the glycans contain terminal sialic acid residues. These two sites, Asn25 and Asn120, were chosen for in silico glycosylation in this study. Here, from extensive standard molecular dynamics simulations and biased simulations, we propose a molecular mechanism for this behavior based on spontaneously-formed charge-paired hydrogen bonding interactions between the negatively-charged sialic acid residues and positively-charged Arg sidechains known to be critically important for binding to HA, which itself is negatively charged. Such intramolecular hydrogen bonds would preclude associations critical to hyaluronan binding. This observation suggests how CD44 and related glycoprotein binding is regulated by sialylation as cellular environments fluctuate. PMID- 25116634 TI - Toward an effective long-term strategy for preventing motor vehicle crashes and injuries. AB - Casualties due to motor vehicle crashes (MVCs) include some 40,000 deaths each year in the United States and one million deaths worldwide. One strategy that has been recommended for improving automobile safety is to lower speed limits and enforce them with speed cameras. However, motor vehicles can be hazardous even at low speeds whereas properly protected human beings can survive high-speed crashes without injury. Emphasis on changing driver behavior as the focus for road safety improvements has been largely unsuccessful; moreover, drivers today are increasingly distracted by secondary tasks such as cell phone use and texting. Indeed, the true limiting factor in vehicular safety is the capacity of human beings to sense and process information and to make rapid decisions. Given that dramatic reductions in injuries and deaths from MVCs have occurred over the past century due to improvements in safety technology, despite increases in the number of vehicles on the road and miles driven per vehicle, we propose that an effective long-term strategy for reducing MVC-related injury would be continued technological innovation in vehicle design, aimed at progressively removing the driver from routine operational decision-making. Once this is achieved, high rates of speed could be achieved on open highways, with minimal risk of crashes and injury to occupants and pedestrians. PMID- 25116635 TI - Global monitoring of water supply and sanitation: history, methods and future challenges. AB - International monitoring of drinking water and sanitation shapes awareness of countries' needs and informs policy, implementation and research efforts to extend and improve services. The Millennium Development Goals established global targets for drinking water and sanitation access; progress towards these targets, facilitated by international monitoring, has contributed to reducing the global disease burden and increasing quality of life. The experiences of the MDG period generated important lessons about the strengths and limitations of current approaches to defining and monitoring access to drinking water and sanitation. The methods by which the Joint Monitoring Programme (JMP) of WHO and UNICEF tracks access and progress are based on analysis of data from household surveys and linear regression modelling of these results over time. These methods provide nationally representative and internationally comparable insights into the drinking water and sanitation facilities used by populations worldwide, but also have substantial limitations: current methods do not address water quality, equity of access, or extra-household services. Improved statistical methods are needed to better model temporal trends. This article describes and critically reviews JMP methods in detail for the first time. It also explores the impact of, and future directions for, international monitoring of drinking water and sanitation. PMID- 25116636 TI - The association between season of pregnancy and birth-sex among Chinese. AB - OBJECTIVE: although numerous studies have reported the association between birth season and sex ratio, few studies have been conducted in subtropical regions in a non-Western setting. The present study assessed the effects of pregnancy season on birth sex ratio in China. METHODS: We conducted a national population-based retrospective study from 2006-2008 with 3175 children-parents pairs enrolled in the Northeast regions of China. Demographics and data relating to pregnancy and birth were collected and analyzed. A multiple logistical regression model was fitted to estimate the regression coefficient and 95% confidence interval (CI) of refractive error for mother pregnancy season, adjusting for potential confounders. RESULTS: After adjusting for parental age (cut-off point was 30 years), region, nationality, mother education level, and mother miscarriage history, there is a significant statistical different mother pregnancy season on birth-sex. Compared with mothers who were pregnant in spring, those pregnant in summer or winter had a high probability of delivering girls (p < 0.05). The birth sex ratio varied with months. CONCLUSIONS: Our results suggested that mothers pregnant in summer and winter were more likely to deliver girls, compared with those pregnant in spring. Pregnancy season may play an important role in the birth-sex. PMID- 25116638 TI - Haptic discrimination of distance. AB - While quite some research has focussed on the accuracy of haptic perception of distance, information on the precision of haptic perception of distance is still scarce, particularly regarding distances perceived by making arm movements. In this study, eight conditions were measured to answer four main questions, which are: what is the influence of reference distance, movement axis, perceptual mode (active or passive) and stimulus type on the precision of this kind of distance perception? A discrimination experiment was performed with twelve participants. The participants were presented with two distances, using either a haptic device or a real stimulus. Participants compared the distances by moving their hand from a start to an end position. They were then asked to judge which of the distances was the longer, from which the discrimination threshold was determined for each participant and condition. The precision was influenced by reference distance. No effect of movement axis was found. The precision was higher for active than for passive movements and it was a bit lower for real stimuli than for rendered stimuli, but it was not affected by adding cutaneous information. Overall, the Weber fraction for the active perception of a distance of 25 or 35 cm was about 11% for all cardinal axes. The recorded position data suggest that participants, in order to be able to judge which distance was the longer, tried to produce similar speed profiles in both movements. This knowledge could be useful in the design of haptic devices. PMID- 25116639 TI - The four-year course of major depressive disorder: the role of staging and risk factor determination. AB - BACKGROUND: Much is still unclear about the mechanisms underlying the course of major depressive disorder (MDD). This study aimed to identify risk factors that predict a poor prognosis of MDD while taking into consideration its chronicity at baseline. METHODS: In patients with MDD (n = 767), we examined whether baseline clinical factors, sociodemographics, childhood trauma, personality and life events predicted the 4-year course (i.e., sustained recovery, temporary recovery and chronic course) of MDD. Baseline chronicity of MDD was taken into account by testing whether associations were different for patients with nonchronic versus chronic MDD at baseline. RESULTS: In patients with nonchronic MDD at baseline, 27.8% developed a chronic disorder during follow-up, whereas 53.0% of patients with chronic MDD at baseline had a persistent chronic disorder during follow-up. Severity of MDD, childhood trauma and greater age were important general risk factors for a poor prognosis, independent of MDD chronicity at baseline. In contrast, low extraversion was only important for the course of nonchronic MDD at baseline, while higher education and negative life events (in patients with high neuroticism) were only relevant for the course of chronic MDD at baseline. CONCLUSIONS: One out of 4 patients with nonchronic MDD progressed to a chronic disorder, while half of the patients with chronic MDD remained chronic during follow-up. Since several risk factors for a poor prognosis differed for patients with nonchronic and chronic MDD at baseline, treatment targets should be adjusted for current chronicity of MDD. PMID- 25116637 TI - Toxicological effects of nickel chloride on IgA+ B Cells and sIgA, IgA, IgG, IgM in the intestinal mucosal immunity in broilers. AB - The objective of this study was to investigate the toxicological effects of dietary NiCl2 on IgA+ B cells and the immunoglobulins including sIgA, IgA, IgG and IgM in the small intestine and cecal tonsil of broilers by the methods of immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Two hundred and forty one-day-old avian broilers were randomly divided into four groups and fed on a control diet and three experimental diets supplemented with 300, 600, and 900 mg/kg NiCl2 for 42 days. Compared with the control group, the IgA+ B cell number and the sIgA, IgA, IgG, and IgM contents in the NiCl2-treated groups were significantly decreased (p < 0.05 or p < 0.01). It was concluded that dietary NiCl2 in the excess of 300 mg/kg had negative effects on the IgA+ B cell number and the above mentioned immunoglobulin contents in the small intestine and the cecal tonsil. NiCl2-reduced sIgA, IgA, IgG and IgM contents is due to decrease in the population and/or the activation of B cell. The results suggest that NiCl2 at high levels has intestinal mucosal humoral immunotoxicity in animals. PMID- 25116641 TI - Distribution of potato spindle tuber viroid in reproductive organs of petunia during its developmental stages. AB - Embryo infection is important for efficient seed transmission of viroids. To identify the major pattern of seed transmission of viroids, we used in situ hybridization to histochemically analyze the distribution of Potato spindle tuber viroid (PSTVd) in each developmental stage of petunia (flowering to mature seed stages). In floral organs, PSTVd was present in the reproductive tissues of infected female * infected male and infected female * healthy male but not of healthy female * infected male before embryogenesis. After pollination, PSTVd was detected in the developed embryo and endosperm in all three crosses. These findings indicate that PSTVd is indirectly delivered to the embryo through ovule or pollen during the development of reproductive tissues before embryogenesis but not directly through maternal tissues as cell-to-cell movement during embryogenesis. PMID- 25116642 TI - Molecular genetic analysis of cucumber mosaic virus populations infecting pepper suggests unique patterns of evolution in Korea. AB - Studying genetic structure and diversity of viruses is important to understand the evolutionary mechanisms that generate and maintain variations in viral populations. Cucumber mosaic virus (CMV) is endemic in most pepper fields in Korea. Currently, no effective methods for control of CMV are available due to many environmental and biological factors such as the extensive evolutionary capacity of CMV. Thus, analyzing the genetic structure of CMV populations may facilitate the development of strategies for the control of CMV. In this study, 252 pepper (Capsicum annuum) samples showing virus symptoms were collected by field surveys performed throughout Korea in 2007. Reverse-transcription polymerase chain reaction analyses revealed that, in total, 165 collected samples were infected with CMV. Forty-five CMV isolates were randomly selected within each regional subpopulation and analyzed by full-genome sequencing. Analyses of genetic diversity showed that the 2b gene of CMV is under weaker purifying selection than the other genes. Based on the phylogenetic analysis of RNA1, the CMV isolates from pepper were divided into three clusters in subgroup I. Our full genome sequence-based molecular analyses of the CMV Korean population suggest that the subpopulations of CMV have been geographically localized in pepper fields in Korea. PMID- 25116643 TI - Pollen transmission of asparagus virus 2 (AV-2) may facilitate mixed infection by two AV-2 isolates in asparagus plants. AB - Asparagus virus 2 (AV-2) is a member of the genus Ilarvirus and thought to induce the asparagus decline syndrome. AV-2 is known to be transmitted by seed, and the possibility of pollen transmission was proposed 25 years ago but not verified. In AV-2 sequence analyses, we have unexpectedly found mixed infection by two distinct AV-2 isolates in two asparagus plants. Because mixed infections by two related viruses are normally prevented by cross protection, we suspected that pollen transmission of AV-2 is involved in mixed infection. Immunohistochemical analyses and in situ hybridization using AV-2-infected tobacco plants revealed that AV-2 was localized in the meristem and associated with pollen grains. To experimentally produce a mixed infection via pollen transmission, two Nicotiana benthamiana plants that were infected with each of two AV-2 isolates were crossed. Derived cleaved-amplified polymorphic sequence analysis identified each AV-2 isolate in the progeny seedlings, suggesting that pollen transmission could indeed result in a mixed infection, at least in N. benthamiana. PMID- 25116644 TI - Co-C dissociation of adenosylcobalamin (coenzyme B12): role of dispersion, induction effects, solvent polarity, and relativistic and thermal corrections. AB - Quantum-chemical cluster modeling is challenged in the limit of large, soft systems by the effects of dispersion and solvent, and well as other physical interactions. Adenosylcobalamin (AdoCbl, coenzyme B12), as one of the most complex cofactors in life, constitutes such a challenge. The cleavage of its unique organometallic Co-C bond has inspired multiple studies of this cofactor. This paper reports the fully relaxed potential energy surface of Co-C cleavage of AdoCbl, including for the first time all side-chain interactions with the dissociating Ado group. Various methods and corrections for dispersion, relativistic effects, solvent polarity, basis set superposition error, and thermal and vibrational effects were investigated, totaling more than 550 single point energies for the large model. The results show immense variability depending on method, including solvation, functional type, and dispersion, challenging the conceived accuracy of methods used for such systems. In particular, B3LYP-D3 seems to severely underestimate the Co-C bond strength, consistent with previous results, and BP86 remains accurate for cobalamins when dispersion interactions are accounted for. PMID- 25116645 TI - Dual drug release from core-shell nanoparticles with distinct release profiles. AB - Multiple drug combination is a promising strategy in biomedical fields, such as cancer chemotherapy and tissue engineering. With the aim of codelivering multiple drugs with different characteristics, immiscible and miscible liquids were utilized to fabricate nanoparticles of polyvinylpyrrolidone/poly(lactic-co glycolic acid) (PLGA) and poly(epsilon-caprolactone)/PLGA with distinct core shell structure by coaxial electrospray. Each kind of nanoparticles can encapsulate the hydrophilic rhodamine B and hydrophobic naproxen in one single step efficiently. Encapsulation efficiency was over 85%. The different release patterns of dual-drug encapsulated were demonstrated when the drug location swapped, attributing to the distinct core-shell structures of nanoparticles and the interaction between drug molecules and carrier polymers. Meanwhile, the release profiles of encapsulated drugs with different loading amount were investigated as well. Dual drug release profiles from nanoparticles were affected by the unique architecture of nanocarriers (porous and core-shell structure), physical properties of polymers, and drugs. In addition, polymer-drug and drug drug molecular interaction may take an important role in drug release behaviors. The results suggested that the distinct release kinetics of multiple drugs fabricated by coaxial electrospray can be obtained and tuned to fulfill the clinical requirement in combination therapy. PMID- 25116646 TI - Energy transfer on demand: photoswitch-directed behavior of metal-porphyrin frameworks. AB - In this paper, a photochromic diarylethene-based derivative that is coordinatively immobilized within an extended porphyrin framework is shown to maintain its photoswitchable behavior and to direct the photophysical properties of the host. In particular, emission of a framework composed of bis(5-pyridyl-2 methyl-3-thienyl)cyclopentene (BPMTC) and tetrakis(4-carboxyphenyl)porphyrin (H4TCPP) ligands anchored by Zn(2+) ions can be altered as a function of incident light. We attribute the observed cyclic fluorescence behavior of the synthesized porphyrin-BPMTC array to activation of energy transfer (ET) pathways through BPMTC photoisomerization. Time-resolved photoluminescence measurements show a decrease in average porphyrin emission lifetime upon BPMTC insertion, consistent with an ET-based mechanism. These studies portend the possible utilization of photochromic ligands to direct chromophore behavior in large light-harvesting ensembles. PMID- 25116647 TI - Are insights from Indigenous health shaping a paradigm shift in health promotion praxis in Australia? AB - Health promotion really is at a cross-road. Traditionally guided by the Ottawa Charter, it has been thought of as principle-guided actions, processes and technique, as well as outcomes or results. Health promotion has been characterised by its products and some even call it theory. In Australia, public funding for health promotion has, for many years, shaped its practice into behaviour change interventions. However, governments around the country are reconsidering their investments, evidenced by ideologically motivated policy shifts and associated substantial funding cuts. Recently, themes of empowerment, community control and community agency have emerged as new directions for future health promotion praxis and reports of activism-based approaches that seek to mobilise community energies around sexual health inequity have started to appear in the literature. Noting parallel developments in the social determinants and social change discourses, this paper posits that cutting edge health promotion efforts by Indigenous communities in Australia are shaping a new approach with potentially global application. PMID- 25116648 TI - Using kinematics and a dynamical systems approach to enhance understanding of clinically observed aberrant movement patterns. AB - The objective of this technical paper is to demonstrate how graphing kinematic data to represent body segment coordination and control can assist clinicians and researchers in understanding typical and aberrant human movement patterns. Aberrant movements are believed to be associated with musculoskeletal pain and dysfunction. A dynamical systems approach to analysing movement provides a useful way to study movement control and coordination. Continuous motion angle-angle and coupling angle-movement cycle graphs provide information about coordinated movement between body segments, whereas phase-plane graphs provide information about neuromuscular control of a body segment. Examples demonstrate how a dynamical systems approach can be used to represent (1) typical movement patterns of the lumbopelvic and shoulder regions; (2) aberrant coordination in an individual with low back pain who presented with altered lumbopelvic rhythm; and (3) aberrant control of shoulder movement in an individual with observed scapular dysrhythmia. Angle-angle and coupling angle-movement cycle graphs were consistent with clinical operational definitions of typical and altered lumbopelvic rhythm. Phase-plane graphs illustrated differences in scapular control between individuals having typical scapular motion and an individual with scapular dysrhythmia. Angle-angle, coupling angle-movement cycle, and phase-plane graphs provide information about the amount and timing of segmental motion, which clinicians assess when they observe movements. These approaches have the potential to (1) enhance understanding of typical and aberrant movement patterns; (2) assist with identifying underlying movement impairments that contribute to aberrant movements: and (3) improve clinicians' ability to visually assess and categorize functional movements. PMID- 25116651 TI - Luminescent and transparent nanopaper based on rare-earth up-converting nanoparticle grafted nanofibrillated cellulose derived from garlic skin. AB - Highly flexible, transparent, and luminescent nanofibrillated cellulose (NFC) nanopaper with heterogeneous network, functionalized by rare-earth up-converting luminescent nanoparticles (UCNPs), was rapidly synthesized by using a moderate pressure extrusion paper-making process. NFC was successfully prepared from garlic skin using an efficient extraction approach combined with high frequency ultrasonication and high pressure homogenization after removing the noncellulosic components. An efficient epoxidation treatment was carried out to enhance the activity of the UCNPs (NaYF4:Yb,Er) with oleic acid ligand capped on the surface. The UCNPs after epoxidation then reacted with NFC in aqueous medium to form UCNP grafted NFC nanocomposite (NFC-UCNP) suspensions at ambient temperature. Through the paper-making process, the assembled fluorescent NFC-UCNP hybrid nanopaper exhibits excellent properties, including high transparency, strong up-conversion luminescence, and good flexibility. The obtained hybrid nanopaper was characterized by transmission electron microscopy (TEM), atomic force microscope (AFM), Fourier transform infrared spectroscopy (FTIR), field emission-scanning electron microscope (FE-SEM), up-conversion luminescence (UCL) spectrum, and ultraviolet and visible (UV-vis) spectrophotometer. The experimental results demonstrate that the UCNPs have been successfully grafted to the NFC matrix with heterogeneous network. And the superiorly optical transparent and luminescent properties of the nanopaper mainly depend on the ratio of UCNPs to NFC. Of importance here is that, NFC and UCNPs afford the nanopaper a prospective candidate for multimodal anti-counterfeiting, sensors, and ion probes applications. PMID- 25116649 TI - Effector-dependent neglect and splenial disconnection: a spherical deconvolution tractography study. AB - We present the case of a patient with left homonymous hemianopia and chronic left neglect consequent to a stroke in the occipito-temporal regions of the right hemisphere. When the patient performed cancellation tasks with her right (dominant) hand, she had severe and persistent left neglect at retest 7 and 8 years after onset. However, her performance on line bisection was invariably within normal limits. Strikingly, performance on cancellation tests reverted to normal when the patient used her left hand. White matter tractography using spherical deconvolution demonstrated damage to the splenium of the corpus callosum, as well as a relative preservation of the right fronto-parietal network. Effector-dependent neglect may occur because splenial disconnection deprives the right fronto-parietal network from visual information processed by the left hemisphere. Consequently, spatial exploration reverts to normal when the patient uses her left hand, thus involving more directly the fronto-parietal attentional networks in the right-hemisphere. PMID- 25116652 TI - Food beliefs and practices during pregnancy in Ghana: implications for maternal health interventions. AB - Ghanaian women's food beliefs and practices during pregnancy and the scope for developing more effective maternal health interventions were explored in this study. Thirty-five multiethnic Ghanaian women between the ages of 29 and 75 were interviewed about pregnancy food beliefs and practices. I show that, based on the data analysis, their knowledge about food was drawn from lifeworlds (family and friends), educational settings, health professionals, mass media, and body-self knowledge (unique pregnancy experiences). Core lay ideas converged with expert knowledge on maternal health nutrition. Multiple external factors (e.g., economics, cultural representations of motherhood) and internal factors (e.g., the unpredictable demands of the pregnant body) influenced pregnancy food practices. I suggest and discuss a need for culturally situated multilevel interventions. PMID- 25116653 TI - Water adsorption in UiO-66: the importance of defects. AB - Simulated adsorption isotherms for water in UiO-66 illustrate that defects in the form of missing linkers make this MOF more hydrophilic. Heats of adsorption and density plots further confirm the effect of defects on adsorption of water in UiO 66 at low loadings. In addition, water and CO2 isotherms indicate that not only the amount of defects but their locations within the material affect the loading of guest molecules. PMID- 25116650 TI - A magnetic carbon sorbent for radioactive material from the Fukushima nuclear accident. AB - Here we present the first report of a carbon-gamma-Fe2O3 nanoparticle composite of mesoporous carbon, bearing COOH- and phenolic OH- functional groups on its surface, a remarkable and magnetically separable adsorbent, for the radioactive material emitted by the Fukushima Daiichi nuclear power plant accident. Contaminated water and soil at a level of 1,739 Bq kg(-1) ((134)Cs and (137)Cs at 509 Bq kg(-1) and 1,230 Bq kg(-1), respectively) and 114,000 Bq kg(-1) ((134)Cs and (137)Cs at 38,700 Bq kg(-1) and 75,300 Bq kg(-1), respectively) were decontaminated by 99% and 90% respectively with just one treatment carried out in Nihonmatsu city in Fukushima. Since this material is remarkably high performance, magnetically separable, and a readily applicable technology, it would reduce the environmental impact of the Fukushima accident if it were used. PMID- 25116655 TI - Supervision in neuropsychological assessment: a survey of training, practices, and perspectives of supervisors. AB - Within the psychology supervision literature, most theoretical models and practices pertain to general clinical or counseling psychology. Supervision specific to clinical neuropsychology has garnered little attention. This survey study explores supervision training, practices, and perspectives of neuropsychology supervisors. Practicing neuropsychologists were invited to participate in an online survey via listservs and email lists. Of 451 respondents, 382 provided supervision to students, interns, and/or fellows in settings such as VA medical centers (37%), university medical centers (35%), and private practice (15%). Most supervisors (84%) reported supervision was discussed in graduate school "minimally" or "not at all." Although 67% completed informal didactics or received continuing education in supervision, only 27% reported receiving training specific to neuropsychology supervision. Notably, only 39% were satisfied with their training in providing supervision and 77% indicated they would likely participate in training in providing supervision, if available at professional conferences. Results indicate that clinical neuropsychology as a specialty has paid scant attention to developing supervision models and explicit training in supervision skills. We recommend that the specialty develop models of supervision for neuropsychological practice, supervision standards and competencies, training methods in provision of supervision, and benchmark measures for supervision competencies. PMID- 25116656 TI - Bit-related lesions in Icelandic competition horses. AB - BACKGROUND: Oral lesions related to the use of the bit and bridle are reported to be common findings in horses worldwide and represent an important animal welfare issue. In order to provide an overview of bit-related lesions in Icelandic competition horses, a field examination of the rostral part of the oral cavity was performed in 424 competition horses coming to the two major national horse events in Iceland in 2012. Records from repeated examination of 77 horses prior to the finals were used to assess potential risk factors. RESULTS: Mild lesions were recorded in 152 horses (36%) prior to the preliminary rounds. They were most often located in the commissures of the lips and the adjacent buccal mucosa (n=111). Severe lesions were found in 32 (8%) horses. For 77 horses examined prior to the finals, the frequency of findings in the area of the mandibular interdental space (bars of the mandible) had increased from 8% to 31% (P<0.0001). These findings were most often (16/24) regarded as severe. The presence of lesions on the bars was strongly associated to the use of curb bits with a port (OR=75, P=0.009). CONCLUSIONS: Bit-related lesions were found to be a general problem in Icelandic competition horses. The type of bits used influenced both the location and the severity of the lesions. The use of curb bits with a port was found to be a decisive risk factor for lesions on the bars of the mandible, most of which were regarded as severe. The results also raised questions about the head and neck carriage demanded for the competition horses. PMID- 25116657 TI - Dynamic propensity as an indicator of heterogeneity in room-temperature ionic liquids. AB - We investigate the dynamic propensity in a coarse-grained model of a room temperature ionic liquid via molecular dynamics simulations. Dynamic propensity is defined as the average of squared displacements for each ion during a given time interval over the isoconfigurational ensemble. As the temperature is lowered, distributions of the dynamic propensity develop fat tails at high values, indicating the presence of dynamic heterogeneity in the system. The increase in the heterogeneity for the cation is more evident than that for the anion, and a high propensity exhibits a large variance in the isoconfigurational ensemble, implying that dynamic propensity is related to ions' motions at a large length scale, rather than a direct measure of the individual ion dynamics. In addition, large non-Gaussian parameters observed for small dynamic propensities reveal intermittent dynamical behaviors of ions. In order to reveal the origin of the dynamic heterogeneity in a room-temperature ionic liquid, a possible correlation between the mobility and dynamic propensity is further probed. It is observed that spatial distributions of the dynamic propensity coincide with those of the mobility. The results suggest a possible connection between the structure and heterogeneous dynamics on large length scales. PMID- 25116658 TI - Gram-negative infections in pediatric and neonatal intensive care units of Latin America. AB - In order to review the epidemiology of Gram-negative infections in the pediatric and neonatal intensive care units (PICUs and NICUs) of Latin America a systematic search of PubMed and targeted search of SciELO was performed to identify relevant articles published since 2005. Independent cohort data indicated that overall infection rates were higher in Latin American PICUs and NICUs versus developed countries (range, 5%-37% vs 6%-15%, respectively). Approximately one third of Latin American patients with an acquired PICU or NICU infection died, and crude mortality was higher among extremely low-birth-weight infants and those with an infection caused by Gram-negative bacteria. In studies reporting > 100 isolates, the frequency of Gram-negative pathogens varied from 31% (Colombia) to 63% (Mexico), with Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli the predominant pathogens in almost all countries, and Acinetobacter spp. and Serratia spp. isolated sporadically. The activity of quinolones and third generation cephalosporins against P. aeruginosa, Acinetobacter spp., and Enterobacteria was seriously compromised, coincident with a high prevalence of circulating extended-spectrum beta-lactamases. Furthermore, we identified two observational studies conducted in Chile and Brazil reporting infections by P. aeruginosa and Acinetobacter baumannii in PICUs, demonstrating resistance to carbapenems, and two outbreaks of carbapenem-resistant K. pneumoniae in Colombia and Brazil. The endemicity of multidrug-resistant Gram-negative infections in Latin American PICUs and NICUs is punctuated by intermittent clonal outbreaks. The problem may be alleviated by ensuring ICUs are less crowded, increasing staffing levels of better-trained health care personnel, and implementing antimicrobial stewardship and surveillance programs. PMID- 25116659 TI - An overview of extended-spectrum beta-lactamases in veterinary medicine and their public health consequences. AB - Serious human and animal infections caused by bacteria are usually treated with beta-lactams. Extended-spectrum beta-lactamases (ESBLs) constitute the most clinically and economically important enzymes that are able to hydrolyze and inactivate beta-lactam antibiotics in veterinary medicine. The spread of ESBLs represents a serious threat to healthcare systems, drastically undermining therapeutic options. The relationship between drug usage and the emergence of resistance has been extensively reported. Nevertheless, the use of antimicrobials in veterinary medicine and the emergence of ESBLs in animals remains a matter of debate. Moreover, there is still controversy about whether antibiotic usage in farm animals poses a potential public health risk. This review will (i) deal with aspects related to the presence of ESBLs in veterinary medicine, (ii) its link with human medicine, and (iii) discuss strategies to be implemented to preserve antimicrobial effectiveness. New insights relative to old questions concerning antimicrobial use in domestic animals are also presented. PMID- 25116660 TI - Diagnosis of leishmaniasis. AB - Leishmaniasis is a clinically heterogeneous syndrome caused by intracellular protozoan parasites of the genus Leishmania. The clinical spectrum of leishmaniasis encompasses subclinical (not apparent), localized (skin lesion), and disseminated (cutaneous, mucocutaneous, and visceral) infection. This spectrum of manifestations depends on the immune status of the host, on the parasite, and on immunoinflammatory responses. Visceral leishmaniasis causes high morbidity and mortality in the developing world. Reliable laboratory methods become mandatory for accurate diagnosis, especially in immunocompromised patients such as those infected with HIV. In this article, we review the current state of the diagnostic tools for leishmaniasis, especially the serological test. PMID- 25116661 TI - Antimicrobial and molecular analysis of Salmonella serovar Livingstone strains isolated from humans in Tunisia and Belgium. AB - INTRODUCTION: Salmonella Livingstone is one of the most common serotypes responsible for nosocomial outbreaks in Tunisia. In this study, 42 isolates of Salmonella Livingstone were analyzed. Most of these were isolated from humans (31 strains from Tunisia and 9 strains from Belgium) and 2 isolates came from food products (beef and pork). METHODOLOGY: All strains were characterized by antibiogram, multilocus sequence typing (MLST), and virulotyping. This last technique was carried out by simple PCR of five chromosomal genes (agfA, hin/H2, iroB, phoP/Q, and slyA) and two plasmid genes (spvA and spvC). RESULTS: All Tunisian strains were resistant to amoxicillin, amoxicillin-clavulanic acid, ticarcillin, cefalotin, gentamicin, and kanamycin. They were also resistant to third-generation cephalosporin antibiotics (cefotaxim and ceftazidim). Belgian isolates were susceptible to all antibiotics tested. Further to MLST analyses, Tunisian strains belonged to the same sequence type, ST543. For Belgian isolates, eight strains had a ST543 profile, two strains had a ST638 profile, and one strain had a ST457 profile. Analyses of the virulence gene contents showed that strains isolated in different years and from different origins had the same virulence profile. These carried all five chromosomal genes and lacked plasmid located virulence genes spvA and spvC. CONCLUSIONS: A combination of different typing methods showed that the majority of Belgian strains and all Tunisian strains were closely related; they belonged to the same sequence type (ST543) and had the same virulence profile, but different antibiotic resistance profiles depended on the country of origin. PMID- 25116662 TI - A three-year review of antimicrobial resistance of Salmonella enterica serovars Typhi and Paratyphi A in Pakistan. AB - INTRODUCTION: Enteric fever is among the most common bacteraemic illnesses in South Asia. Multidrug resistance as well as fluoroquinolone resistance has severely limited therapeutic options in high disease burden countries such as Pakistan. This review was conducted to determine the frequency of drug-resistant Salmonella enterica serovar Typhi (S.Typhi) and Salmonella enterica serovar Paratyphi A (S. Paratyphi A) between 2009 and 2011. METHODOLOGY: This study was a review of laboratory data. The antibiotic susceptibility of typhoidal Salmonellae isolated from blood cultures submitted to the Aga Khan University Hospital's laboratory from all over Pakistan between January 2009 and December 2011 were reviewed. RESULTS: The sensitivity data of 4,323 positive isolates of S. Typhi and S. Paratyphi A isolated during the three-year period were reviewed. The majority of isolates were S. Typhi (59.6%).Over three years, the incidence of multidrug-resistant (MDR) S.Typhi remained high, ranging from 64.8%-66.0%, while MDR S. Paratyphi A decreased from 4.2% to 0.6%. Fluoroquinolone resistance increased for S. Typhi from 84.7% to 91.7%. Cefixime- and ceftriaxone-resistant S. Typhi were isolated in two children. CONCLUSIONS: Our results show high rates of multidrug and fluoroquinolone resistance among S. Typhi and S. Paratyphi. The occurrence of two cases of ceftriaxone resistance is alarming. PMID- 25116663 TI - Low rifampicin concentrations in tuberculosis patients with HIV infection. AB - INTRODUCTION: The efficacy of tuberculosis (TB) treatment in Human Immunodeficiency Syndrome (HIV) co-infected patients may be compromised by genetic and pharmacokinetic variation in drug disposition. Rifampicin is a critical component of TB treatment. We investigated the influence of drug transporter gene polymorphisms on rifampicin concentrations in TB-HIV co-infected patients in Durban, South Africa. METHODOLOGY: Rifampicin concentrations were measured 2.5 hours post-dose (approximated peak, C2.5 hr) in patients receiving either 450mg or 600mg rifampicin, randomized to either integrated or sequential antiretroviral treatment. Patients were genotyped for SLCO1B1 (rs4149032) polymorphisms. A mixed effects regression model was fitted to assess the influence of various factors on rifampicin concentrations. TB recurrence rates were also estimated. RESULTS: In 57 patients, median (IQR) C2.5 hr was 3.6 (2.8 5.0) ug/mL. Polymorphism frequency in the SLCO1B1 (rs4149032) drug transporter gene was high (0.76) and was associated with low median rifampicin C2.5 hr, 3.7 (2.8-5.0) ug/mL in the heterozygous and 3.4 (2.7-4.7) ug/mL in the homozygous variant carriers. Concentrations were also low in males (p < 0.0001) and those with low haemoglobin (p = 0.02). Although reinfection could not be distinguished from reactivation for the 43 patients followed post trial, the incidence of TB recurrence was 7.1 per 100 person-years. Of the eight patients in whom TB recurred, seven had the polymorphism. CONCLUSION: Approximated peak rifampicin concentrations were well below the recommended target range of 8 to 24 ug/mL in this patient population with its high frequency of the SLCO1B1 (rs4149032) polymorphism. Increased rifampicin dosage may be warranted in African, HIV- TB co infected patients. PMID- 25116664 TI - Oropharyngeal tularemia cases admitted to a military hospital in Ankara, Turkey. AB - INTRODUCTION: This study aimed to review the possible sources of infection of 16 oropharyngeal tularemia hospital cases, and to document their epidemiological and demographical characteristics, laboratory findings, treatment methods, and treatment results. METHODOLOGY: Sixteen cases from a Turkish military hospital between January 2011 and December 2012 were retrospectively evaluated. The age, sex, occupation, place of residence, symptoms, duration of symptoms, laboratory results, treatment and duration, and treatment results were recorded. Tularemia was diagnosed through tularemia-specific tests once the other conditions that may have caused lymphadenopathy were excluded. RESULTS: Twelve of the patients included in this study were males. The average age of the patients was 32.1 +/- 17.2 years. Sore throat, fatigue, and fever were the most frequent symptoms. The mean duration of symptoms was 21.6 +/- 6.9 days. All the patients had been treated for tonsillopharyngitis in primary healthcare institutions previously. However, despite the treatment, cervical lymphadenopathy had developed in these cases. Patients were given streptomycin, doxycycline, and ciprofloxacin monotherapy or in combination. Ten of the cases fully recovered, while five required surgical lymph node drainage. Spontaneous drainage occurred in the single remaining case. CONCLUSIONS: Turkey is considered to be an endemic country with regards to tularemia. Prompt diagnosis and proper treatment of the disease is imperative in providing cure. Since it can be potentially confused with tuberculous lymphadenitis, differential diagnosis is vital. Patients presenting with a condition of tonsillopharyngitis in endemic areas must be carefully monitored. PMID- 25116665 TI - Clinical characteristics and risk factors of infections caused by Stenotrophomonas maltophilia in a hospital in northwest China. AB - INTRODUCTION: Stenotrophomonas maltophilia infections have recently increased in importance in China, particularly in intensive care units (ICUs). The aim of this study was to investigate the clinical characteristics and risk factors of S. maltophilia infection in ICU of a hospital in northwest China. METHODOLOGY: The characteristics and outcomes of patients with any type of S. maltophilia infection at Shaanxi Provincial People's Hospital, Shaanxi, China, over a two year period (from July 2011 to June 2013) were studied. S. maltophilia antimicrobial susceptibility was tested with the agar dilution method. The risk factors for all-cause in-hospital mortality were assessed with multivariate logistic regression. RESULTS: Forty patients (median age, 72 years; 77.5% males) with S. maltophilia infection were identified. The main type of infection was lower respiratory tract infection (97.5%); one patient had a bloodstream infection. A total of 97.5% patients were infected with two or more organisms at the same time. The main characteristics of the patients were prolonged use of mechanical ventilation, urethral catheter, and central venous catheter before the infections occurred. The case number of infection was not different in the four seasons. High in vitro sensitivity was observed to minocycline (91.2%), levofloxacin (85.3%), and trimethoprim-sulfamethoxazole (79.4%). Most patients received therapy with a combination of agents. The crude mortality was 50%. By multivariate analysis, low albumin content and hypotension were the independent prognostic factors for mortality. CONCLUSIONS: Appropriate antimicrobial treatment had no positive impact on mortality. The impacts of albumin supplements and increasing blood pressure on mortality require further clinical studies. PMID- 25116666 TI - Sexual behavioral correlates with HSV-2 seroprevalence among pregnant women in Nigeria. AB - INTRODUCTION: The burden of HSV-2 infection, the cause of most cases of genital herpes in Nigeria, varies from region to region; and so are the associated factors. This infection is known to be responsible for several negative pregnancy outcomes. There is currently no documented data on sexual behavioral factors associated with the occurrence of HSV-2 infection or seroprevalence among pregnant women in Nigeria. This study aimed at identifying the sexual behavioral correlates of HSV-2 seroprevalence among pregnant women in Benin City, Nigeria. METHODOLOGY: The cross-sectional study design was adopted and the study took place between November 2011 and June 2012. Four hundred and ten consenting ante natal clinic patients in two major tertiary hospitals in Benin City were consecutively and prospectively included. Data sources were represented by questionnaires, the patient's case records and laboratory investigations. Each patient's serum was analyzed for HSV-2 antibody detection. Data analysis was performed using SPSS version 16. RESULTS: Four hundred and ten patients were enrolled with average age 30.6 years. Seroprevalence of HSV-2 antibody was 47.3%. Sexual behavioral factors that were significantly associated with HSV-2 seroprevalence included early exposure to sexual intercourse, number of sex partners, involvement in polygamous marriages, involvement of husband in extra marital affairs and hormonal contraceptive use. CONCLUSION: The prevalence of HSV 2 among pregnant women in Benin City is high. Public health campaigns aimed at: delaying onset of sexual activity; encouraging monogamous relationships; and emphasizing that hormonal contraceptives do not protect from STI's, are recommended. PMID- 25116667 TI - Prevalence of "anti-HBc alone" among Syrian blood donors. AB - INTRODUCTION: We aimed to evaluate the prevalence of "anti-HBc alone" among Syrian blood donors, highlighting the possibility of representing occult HBV infection. METHODOLOGY: Sera of 3,896 healthy blood donors were tested for both HBsAg and anti-HBc. HBsAg-negative, anti-HBc-positive samples were further tested for the antibodies to HBsAg (anti-HBs), and "anti-HBc alone" sera were tested for HBV DNA. RESULTS: Of 3,830 HBsAg-negative donors, 63 were "anti-HBc alone" donors, five of whom were HBV DNA positive. CONCLUSIONS: Greater consideration should be given to the "anti-HBc alone" serological profile in blood screening, premarital testing, organ transplantation tests, and other HBV transmission related procedures in Syria. PMID- 25116668 TI - Diagnosis and molecular typing of rabies virus in samples stored in inadequate conditions. AB - INTRODUCTION: The exposure of nervous tissue samples to high temperatures affects the sensitivity of rabies virus diagnostic tests, causing degradation of the viral structure. This study evaluated reverse transcriptase polymerase chain reaction (RT-PCR) for the diagnosis and molecular characterization of brain tissue samples in an advanced state of decomposition and poorly conserved viral isolates by comparing it with routine diagnostic tests. METHODOLOGY: A panel of three canine brain samples exposed to controlled decomposition for 7, 15, 30, and 120 days were evaluated using fluorescence antibody test (FAT), mouse inoculation test (MIT), and RT-PCR. In addition, 14 isolates of rabies variants, representing the largest circulation in Argentina, preserved in inadequate cooling for six to eight years were analyzed. Molecular typing of strains was performed using a 159 nucleotide region corresponding to the nucleoprotein gene. RESULTS: The three samples analyzed were positive by RT-PCR at all the decomposition times evaluated, in contrast to results observed with FAT and MIT, which rapidly became negative. In addition, 100% of the inadequately preserved samples were characterized molecularly. The limit of detection of RT-PCR was 0.5 MICDL50/0.03 mL. CONCLUSION: RT-PCR can be useful for rabies diagnosis and typing of putrefying samples or rabies isolates stored in inadequate conditions. PMID- 25116669 TI - Seroprevalence and risk factors for toxoplasmosis in large ruminants in northern Punjab, Pakistan. AB - INTRODUCTION: Toxoplasmosis is a widespread zoonosis that causes significant economic losses due to abortions and other developmental disabilities in livestock animals. The objectives of the current study were to determine the prevalence and associated risk factors of Toxoplasma gondii infection in cattle and buffaloes in northern parts of Punjab, Pakistan, where no such work previously existed. METHODOLOGY: Serum samples obtained from 400 cattle and 422 buffaloes present on different private and government-owned farms were tested for anti-Toxoplasma IgG and anti-Toxoplasma IgM antibodies by using enzyme linked immunosorbent assay (ELISA). Additional data, including water sources, hygienic status at the farm, management practices, size of the herd, and presence of cats in the vicinity of the farm were obtained using a questionnaire in surveys and interviews. RESULTS: The overall prevalence of infection was 19.75% (79/400) in cattle and 15.16% (64/422) in buffaloes. IgG antibodies were found in 75 (18.75%) cattle and 58 (13.74%) buffaloes, while IgM antibodies were found in 9 (2.25%) cattle and 10 (2.37%) buffaloes. Seroprevalence was significantly higher in females and older animals of both species. Seroprevalence was found to be associated with poor hygienic conditions, extensive management practices, and presence of cats in the surrounding areas. No difference of seroprevalence was observed with respect to different breeds, location, water source, and herd size. CONCLUSION: The present study found that T. gondii is prevalent in large ruminants in northern Punjab, and may have important implications for the livestock industry and public health. PMID- 25116670 TI - Prevalence of Trypanosoma cruzi infection in blood donors in El Salvador between 2001 and 2011. AB - INTRODUCTION: El Salvador is regarded as a highly endemic country for Chagas disease, as evidenced by the relatively high estimated positive serology rate for Trypanosoma cruzi among blood donors. This study aimed to identify the factors contributing to this high rate by analyzing changes in T. cruzi seroprevalence. METHODOLOGY: Secondary data were collected from 31 blood banks operated by the Ministry of Health, the Red Cross, the Institute of Salvadoran Social Security, and the Military Hospital. The data were analyzed to determine the number of cases of T. cruzi seropositivity, and the average prevalence of seropositivity by province. Simple linear regression was performed to identify trends in T. cruzi seropositivity. RESULTS: Analysis of the 885,187 blood samples collected between 2001 and 2011 revealed 21,693 cases of transfusion-related infections, with a significant reduction of T. cruzi seropositivity from 3.7% in 2001 to 1.7% in 2011, reflecting a 54% decrease over the course of a decade (R(2) = 89.6%, p > 0.001). T. cruzi seroprevalence decreased in San Salvador, Santa Ana, Sonsonate, and Cuscatlan. In contrast, seroprevalence remained high with no decrease in Ahuachapan and San Vicente, and consistently low in the remainder of the country. CONCLUSIONS: Although the national prevalence of T. cruzi among blood donors has decreased, it remains high in the provinces of Ahuachapan and San Vicente. Strengthening vector control activities and developing an approach for the systematic follow-up of prospective blood donors with positive serology for T. cruzi are required, especially in areas with high seropositivity. PMID- 25116671 TI - Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from patients in Midwest Brazil. AB - INTRODUCTION: Cryptococcosis is a systemic fungal infection that affects humans and animals, mainly due to Cryptococcus neoformans and Cryptococcus gattii. Following the epidemic of acquired immunodeficiency syndrome (AIDS), fungal infections by C. neoformans have become more common among immunocompromised patients. Cryptococcus gattii has primarily been isolated as a primary pathogen in healthy hosts and occurs endemically in northern and northeastern Brazil. We to perform genotypic characterization and determine the in vitro susceptibility profile to antifungal drugs of the Cryptococcus species complex isolated from HIV positive and HIV-negative patients attended at university hospitals in Cuiaba, MT, in the Midwestern region of Brazil. METHODOLOGY: Micromorphological features, chemotyping with canavanine-glycine-bromothymol blue (CGB) agar and genotyping by URA5-RFLP were used to identify the species. The antifungal drugs tested were amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole. Minimum inhibitory concentrations (MICs) were determined according to the CLSI methodology M27-A3. RESULTS: Analysis of samples yelded C. neoformans AFLP1/VNI (17/27, 63.0%) and C. gattii AFLP6/VGII (10/27, 37.0%). The MICs ranges for the antifungal drugs were: amphotericin B (0.5-1 mg/L), fluconazole (1-16 mg/L), flucytosine (1-16 mg/L), itraconazole (0.25-0.12 mg/L) and voriconazole (0.06-0.5 mg/L). Isolates of C. neoformans AFLP1/VNI were predominant in patients with HIV/AIDS, and C. gattii VGII in HIV-negative patients. The genotypes identified were susceptible to the antifungal drugs tested. CONCLUSION: It is worth emphasizing that AFLP6/VGII is a predominant genotype affecting HIV-negative individuals in Cuiaba. These findings serve as a guide concerning the molecular epidemiology of C. neoformans and C. gattii in the State of Mato Grosso. PMID- 25116672 TI - Detection of the novel IMP-38 among carbapenemase-producing Enterobacteriaceae in a university hospital, China. AB - INTRODUCTION: This study set out to investigate the molecular epidemiology of carbapenemase-producing Enterobacteriaceae isolates collected from Xiang Ya Hospital, Hunan, China. METHODOLOGY: The carbapenemase genes from Enterobacteriaceae isolates were determined by PCR and sequencing. Relatedness of Klebsiella pneumoniae isolates was evaluated by pulsed-field gel electrophoresis. RESULTS: Twenty-four out of 738 non-repetitive Enterobacteriaceae isolates harbored carbapenemase genes including IMP-38, a novel IMP-type metallo-enzyme. Nine IMP-38-producing isolates were shown to originate from the same clone and caused a small outbreak in the neonatal ward. CONCLUSIONS: IMP-38, a novel IMP type metallo-enzyme, was one of the predominant types of carbapenemase in the clinical carbapenem-resistant Enterobacteriaceae isolates in our hospital. PMID- 25116673 TI - Risk factors for carbapenem-resistant Acinetobacter baumanii blood stream infections in a neonatal intensive care unit, Delhi, India. AB - INTRODUCTION: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is being increasingly observed and is associated with significant morbidity and mortality in newborns. In this study, we determined the epidemiology, risk factors, and outcomes of blood stream infection (BSI) caused by CRAB in neonates. METHODOLOGY: The clinical charts of neonates who developed Acinetobacter baumannii BSI in the period between 1 January 2010 and 31 December 2012 were reviewed. RESULTS: During the study period, 65 neonates developed Acinetobacter baumannii BSI; 33 were CRAB at an incidence of 0.50 case per 1,000 patient-days. Compared with carbapenem-sensitive Acinetobacter baumannii (CSAB), patients with CRAB BSI had significantly higher prior antimicrobial use, longer duration of ventilation, and late isolation of organisms. Feeding with expressed breast milk was protective. All isolates of Acinetobacter baumenii were sensitive to colistin and tigecycline. The all-cause mortality rates were 27.3% in CRAB and 9.4% in CSAB BSI, respectively (p = 0.074). CONCLUSIONS: Neonatal BSI caused by CRAB was not common but caused high mortality. Feeding with breast milk was protective. Lack of effective antibiotics was the major challenge in treating these patients. PMID- 25116674 TI - Lipolytic activity of Staphylococcus aureus from human wounds, animals, foods, and food-contact surfaces in Brazil. AB - INTRODUCTION: S. aureus is of great importance to public health due to its pathogenicity. This study aimed to evaluate lipase production by S. aureus isolates from different sources. METHODOLOGY: Lipolytic activity was determined using Tween-Calcium agar (48 hours; 35 degrees C). RESULTS: Eighty-six percent of the isolates from human wounds were positive for lipase production. The frequencies of isolates positive for lipase production were 33.3% from cow udders, 15.4% from the nasal cavities of cattle, 82.9% from ricotta cheeses, and 100% and 91.7% from meat- and vegetable-contact surfaces, respectively. CONCLUSION: The production of lipase varied among the isolates according to their source. PMID- 25116675 TI - Transportation of sputum samples in cetylpyridinium chloride for drug resistance studies from remote areas of Odisha, India. AB - INTRODUCTION: Antimicrobial susceptibility testing of Mycobacterium tuberculosis is required for successful treatment of patients, mainly in retreatment cases which necessitate isolation of mycobacteria from sputum samples within 24-48 hours. In situations where transportation of sputum is required, the use of cetylpyridinium chloride (CPC) effectively sustains the viability of mycobacteria up to two weeks. METHODOLOGY: Sputum samples were collected from pulmonary TB patients attending designated microscopy centres (DMC), stored in CPC solution and transported to a culture drug susceptibility testing laboratory using overnight bus transport facilities. For culture, the sputum specimens were processed and inoculated in Lowenstein- Jensen (LJ) medium. Growth on LJ was identified by colony morphology, growth rate and biochemical tests, and transit time was calculated as the time taken from the date of sample collection to the inoculation date. RESULTS: Out of the 816 sputum samples collected in CPC, 691 (84.7%) yielded M. tuberculosis, 97 (11.9%) yielded no growth, 21(2.6%) grew contaminants and 7 (0.8%) were nontuberculous mycobacteria. CPC containing sputum samples processed within two weeks showed 88.6% culture positivity, while positivity was significantly affected beyond two weeks. CONCLUSIONS: CPC is cheap, easy to use, inhibits the growth of other organisms and can effectively be used to transport sputum specimens within two weeks from hard to reach areas to central locations without compromising culture positivity. Bus transport services can also help in reducing delay and the cost of transportation from remote areas. PMID- 25116676 TI - Antiretroviral drug resistance and HIV-1 subtypes among treatment-naive prisoners in Kelantan, Malaysia. AB - INTRODUCTION: The widespread use of highly active antiretroviral therapy (HAART) and continuous reports of HIV-1 strains developing resistance to these drugs is rather alarming, as transmission of resistant viruses to newly infected persons is possible. This study aimed to determine HIV-1 subtypes and the prevalence of primary mutations associated with antiretroviral (ARV) resistance among treatment naive prisoners on the east coast of Malaysia. METHODOLOGY: Viral RNA was extracted from plasma samples of 21 treatment-naive prisoners. Protease (PR) and reverse transcriptase (RT) regions were amplified and sequenced. Stanford HIV database algorithms were used for interpretation of resistance, and phylogenetic analysis was performed for subtype assignment. RESULTS: In the PR gene, no antiviral resistance-associated mutation was detected. For RT-associated mutations, K103N was the most prevalent in sequenced samples (14.3%). Genetic subtyping on the pol gene revealed that the majority of the prisoners were infected with subtype CRF33_01B (52.4%). CONCLUSION: Continuous surveillance of newly infected individuals is required to help strategize the best antiviral treatment for these patients. PMID- 25116677 TI - Higher levels of hepatitis C virus RNA found in blood donors co-infected with HIV as compared to HCV mono-infected donors. AB - INTRODUCTION: Hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infections are public health problems in sub-Saharan countries such as the Republic of Congo. HIV infection could impact the characteristics of HCV infection in co-infected people. We investigated HCV-HIV co-infection among blood donors in Congo. METHODOLOGY: Ninety-nine HIV-positive and/or HCV-seropositive blood donors were selected during screening and subsequently tested for aminotransferases and HCV RNA. RESULTS: A total of 29 donors were found positive for HCV RNA (HCV-infected individuals), including 19/60 (31.66%) HIV donors (co infected) and 10/39 (25.64%) non-HIV donors (mono-infected). Most of the co infected donors (17/19) displayed a high viral load (> 5 log). The median HCV RNA level was at least 2 logs higher in co-infected people. The levels of alanine aminotransferase (ALT) were also slightly higher in co-infected donors than in HCV mono-infected donors. CONCLUSION: This study reports HCV-HIV co-infection among blood donors in Congo and shows that HCV viral load is higher in HIV donors. PMID- 25116678 TI - Hantavirus infection mimicking leptospirosis: how long are we going to rely on clinical suspicion? AB - Hantavirus infections and leptospirosis can have similar clinical and epidemiological features. We present here a case study of a young farmer with fever during the post-flood leptospirosis outbreak in Anuradhapura, Sri Lanka, in 2011. He presented with a classical clinical picture of leptospirosis and was managed and notified as a case of leptospirosis. Retrospective analysis of a stored serum sample confirmed acute hantavirus infection. Diagnosis of newly identified or emerging infectious diseases such as hantavirus infection is challenging due to the lack of diagnostic facilities in developing countries. This case highlights the need for improving diagnostic facilities, educating medical staff, and conducting population-based prospective studies on hantavirus infections in Sri Lanka. PMID- 25116679 TI - Dengue encephalopathy - still an enigma? AB - Dengue encephalopathy or dengue hemorrhagic fever (DHF) with neurological involvement was once considered to be one of the rarer presentations of this infectious agent. In recent years, many such clinical cases have been reported, though they still remain isolated. We hereby report a case of confirmed dengue fever with features of encephalopathy with previously unreported cranial magnetic resonance imaging findings suggestive of extensive involvement of the bilateral cerebellar region, brainstem, and thalami along with peculiar rim enhancement but normal cerebrospinal fluid analysis. PMID- 25116680 TI - Parainfluenza virus 4 presenting with pericardial effusion in an immunocompetent child. PMID- 25116681 TI - Disease prevention: saving lives or reducing health care costs? AB - BACKGROUND: Disease prevention has been claimed to reduce health care costs. However, preventing lethal diseases increases life expectancy and, thereby, indirectly increases the demand for health care. Previous studies have argued that on balance preventing diseases that reduce longevity increases health care costs while preventing non-fatal diseases could lead to health care savings. The objective of this research is to investigate if disease prevention could result in both increased longevity and lower lifetime health care costs. METHODS: Mortality rates for Netherlands in 2009 were used to construct cause-deleted life tables. Data originating from the Dutch Costs of Illness study was incorporated in order to estimate lifetime health care costs in the absence of selected disease categories. We took into account that for most diseases health care expenditures are concentrated in the last year of life. RESULTS: Elimination of diseases that reduce life expectancy considerably increase lifetime health care costs. Exemplary are neoplasms that, when eliminated would increase both life expectancy and lifetime health care spending with roughly 5% for men and women. Costs savings are incurred when prevention has only a small effect on longevity such as in the case of mental and behavioural disorders. Diseases of the circulatory system stand out as their elimination would increase life expectancy while reducing health care spending. CONCLUSION: The stronger the negative impact of a disease on longevity, the higher health care costs would be after elimination. Successful treatment of fatal diseases leaves less room for longevity gains due to effective prevention but more room for health care savings. PMID- 25116682 TI - Evaluation of in vitro cytotoxicity and genotoxicity of copper-zinc alloy nanoparticles in human lung epithelial cells. AB - In the present study, in vitro cytotoxic and genotoxic effect of copper-zinc alloy nanoparticles (Cu-Zn ANPs) on human lung epithelial cells (BEAS-2B) were investigated. XTT test and clonogenic assay were used to determine cytotoxic effects. Cell death mode and intracellular reactive oxygen species formations were analyzed using M30, M65 and ROS Elisa assays. Genotoxic effects were evaluated using micronucleus, comet and gamma-H2AX foci assays. Cu-Zn ANPs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential measurements. Characterization of Cu-Zn ANPs showed an average size of 200nm and zeta potential of -22mV. TEM analyses further revealed the intracellular localization of Cu-Zn ANPs in cytoplasm within 24h. Analysis of micronucleus, comet and gamma-H2AX foci counts showed that exposure to Cu-Zn ANPs significantly induced chromosomal damage as well as single and double stranded DNA damage in BEAS-2B cells. Our results further indicated that exposure to Cu-Zn ANPs significantly induced intracellular ROS formation. Evaluation of M30:M65 ratios suggested that cell death was predominantly due to necrosis. PMID- 25116683 TI - Theoretical study of the transpore velocity control of single-stranded DNA. AB - The electrokinetic transport dynamics of deoxyribonucleic acid (DNA) molecules have recently attracted significant attention in various fields of research. Our group is interested in the detailed examination of the behavior of DNA when confined in micro/nanofluidic channels. In the present study, the translocation mechanism of a DNA-like polymer chain in a nanofluidic channel was investigated using Langevin dynamics simulations. A coarse-grained bead-spring model was developed to simulate the dynamics of a long polymer chain passing through a rectangular cross-section nanopore embedded in a nanochannel, under the influence of a nonuniform electric field. Varying the cross-sectional area of the nanopore was found to allow optimization of the translocation process through modification of the electric field in the flow channel, since a drastic drop in the electric potential at the nanopore was induced by changing the cross-section. Furthermore, the configuration of the polymer chain in the nanopore was observed to determine its translocation velocity. The competition between the strength of the electric field and confinement in the small pore produces various transport mechanisms and the results of this study thus represent a means of optimizing the design of nanofluidic devices for single molecule detection. PMID- 25116684 TI - Rapamycin-Induced apoptosis in HGF-stimulated lens epithelial cells by AKT/mTOR, ERK and JAK2/STAT3 pathways. AB - Hepatocyte growth factor (HGF) induced the proliferation of lens epithelial cells (LECs) and may be a major cause of posterior capsule opacification (PCO), which is the most frequent postoperative complication of cataract surgery. To date, several agents that can block LECs proliferation have been studied, but none have been used in clinic. Recently, accumulating evidence has suggested rapamycin, the inhibitor of mTOR (mammalian target of Rapamycin), was associated with the induction of apoptosis in LECs. The purpose of our study was to investigate the potential effects of rapamycin on HGF-induced LECs and the underlying mechanisms by which rapamycin exerted its actions. Using cell proliferation, cell viability and flow cytometric apoptosis assays, we found that rapamycin potently not only suppressed proliferation but also induced the apoptosis of LECs in a dose dependent manner under HGF administration. Further investigation of the underlying mechanism using siRNA transfection revealed that rapamycin could promote apoptosis of LECs via inhibiting HGF-induced phosphorylation of AKT/mTOR, ERK and JAK2/STAT3 signaling molecules. Moreover, the forced expression of AKT, ERK and STAT3 could induce a significant suppression of apoptosis in these cells after treatment of rapamycin. Together, these findings suggested that rapamycin induced apoptosis in HGF-stimulated LECs is accompanied by inhibition of AKT/mTOR, ERK and JAK2/STAT3 pathways, which supports its use to inhibit PCO in preclinical studies and provides theoretical foundation for future possible practice. PMID- 25116686 TI - Effect of beta-glucan supplementation on acute postprandial changes in fatty acid profile of lymph and serum in pigs. AB - Triglycerides are absorbed by the lymphatic system and have various functions in the body. It has been shown that some types of beta-glucans have a positive effect on the systemic concentrations of cholesterol and lipid, presumably through interference with the absorption of lipid and/or reabsorption of bile acids. In the current study we investigated the acute effects of ingesting 2 g of beta-glucan concentrates derived from barley beta-(1->3)(1->4)-D-glucan or yeast beta-(1->3)(1->6)-D-glucan on fatty acid content and composition in lymph and serum of 10 female pigs (initial weight 34.7+/-1.1 kg) fitted with a permanent catheter in the jejunal lymphatic trunk in a cross-over design. Lymph was collected continuously for 8 h followed by a spot sample taken 24 h after. A significant effect of time after feeding was observed for all fatty acids in serum and for 18:0, 18:2omega6 and 18:3omega3 in lymph, but a significant effect of beta-glucan was only observed for 14:0 (p=0.049) and 22:6omega3 (p=0.048) in lymph and 18:0 (p=0.019) in serum. While the concentration of dietary fatty acids increased postprandially in lymph, the concentration of arachidonic and docahexanoic acid tended to decrease. Furthermore, there was a drop in concentration of all fatty acid in serum 1 h after the meal. PMID- 25116687 TI - Heterosis in early maize ear inflorescence development: a genome-wide transcription analysis for two maize inbred lines and their hybrid. AB - Heterosis, or hybrid vigor, contributes to superior agronomic performance of hybrids compared to their inbred parents. Despite its importance, little is known about the genetic and molecular basis of heterosis. Early maize ear inflorescences formation affects grain yield, and are thus an excellent model for molecular mechanisms involved in heterosis. To determine the parental contributions and their regulation during maize ear-development-genesis, we analyzed genome-wide digital gene expression profiles in two maize elite inbred lines (B73 and Mo17) and their F1 hybrid using deep sequencing technology. Our analysis revealed 17,128 genes expressed in these three genotypes and 22,789 genes expressed collectively in the present study. Approximately 38% of the genes were differentially expressed in early maize ear inflorescences from heterotic cross, including many transcription factor genes and some presence/absence variations (PAVs) genes, and exhibited multiple modes of gene action. These different genes showing differential expression patterns were mainly enriched in five cellular component categories (organelle, cell, cell part, organelle part and macromolecular complex), five molecular function categories (structural molecule activity, binding, transporter activity, nucleic acid binding transcription factor activity and catalytic activity), and eight biological process categories (cellular process, metabolic process, biological regulation, regulation of biological process, establishment of localization, cellular component organization or biogenesis, response to stimulus and localization). Additionally, a significant number of genes were expressed in only one inbred line or absent in both inbred lines. Comparison of the differences of modes of gene action between previous studies and the present study revealed only a small number of different genes had the same modes of gene action in both maize seedlings and ear inflorescences. This might be an indication that in different tissues or developmental stages, different global expression patterns prevail, which might nevertheless be related to heterosis. Our results support the hypotheses that multiple molecular mechanisms (dominance and overdominance modes) contribute to heterosis. PMID- 25116688 TI - Epigenetic determinants of CYP1A1 induction by the aryl hydrocarbon receptor agonist 3,3',4,4',5-pentachlorobiphenyl (PCB 126). AB - Many enzymes involved in xenobiotic metabolism, including cytochrome P450 (CYP) 1A1, are regulated by the aryl hydrocarbon receptor (AhR). 3,3',4,4',5-Penta chlorobiphenyl (PCB 126) is a potent ligand for AhR and can thus induce the expression of CYP1A1. Interestingly, we observed that human carcinoma cell lines derived from different types of epithelial cells displayed divergent degrees of CYP1A1 induction after exposure to PCB 126. Since epigenetic mechanisms are known to be involved in cell type-specific gene expression, we sought to assess the epigenetic determinants of CYP1A1 induction in these carcinoma cell lines. In contrast to HepG2 hepatocarcinoma cells, HeLa cervical carcinoma cells showed significantly lower levels of CYP1A1 mRNA expression following PCB 126 exposure. Our results show that the two cell lines maintained differences in the chromatin architecture along the CYP1A1 promoter region. Furthermore, treatment with the epigenetic modifiers, trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-Aza-dC), significantly increased the expression of CYP1A1 after PCB 126 treatment in HeLa cells. However, we did not observe apparent differences in methylation levels or specific location of CpG DNA methylation between the two cell lines in the analyzed CYP1A1 promoter region. Taken together, our findings suggest that the differences in CYP1A1 expression between HepG2 and HeLa cells are due to differences in the chromatin architecture of the CYP1A1 promoter and thus establish a role of epigenetic regulation in cell-specific CYP1A1 expression. PMID- 25116689 TI - Localization of MLH3 at the centrosomes. AB - Mutations in human DNA mismatch repair (MMR) genes are commonly associated with hereditary nonpolyposis colorectal cancer (HNPCC). MLH1 protein heterodimerizes with PMS2, PMS1, and MLH3 to form MutLalpha, MutLbeta, and MutLgamma, respectively. We reported recently stable expression of GFP-linked MLH3 in human cell lines. Monitoring these cell lines during the cell cycle using live cell imaging combined with confocal microscopy, we detected accumulation of MLH3 at the centrosomes. Fluorescence recovery after photobleaching (FRAP) revealed high mobility and fast exchange rates at the centrosomes as it has been reported for other DNA repair proteins. MLH3 may have a role in combination with other repair proteins in the control of centrosome numbers. PMID- 25116690 TI - Effects of psychotherapy on DNA strand break accumulation originating from traumatic stress. AB - BACKGROUND: Previous research reveals an association between traumatic stress and an increased risk for numerous diseases, including cancer. At the molecular level, stress may increase carcinogenesis via increased DNA damage and impaired DNA repair mechanisms. We assessed DNA breakage in peripheral blood mononuclear cells from individuals with post-traumatic stress disorder (PTSD) and measured the cellular capacity to repair single-strand breaks after exposure to ionizing X radiation. We also investigated the effect of psychotherapy on both DNA breakage and DNA repair. METHODS: In a first study we investigated DNA breakage and repair in 34 individuals with PTSD and 31 controls. Controls were subdivided into 11 trauma-exposed subjects and 20 individuals without trauma exposure. In a second study, we analysed the effect of psychotherapy (Narrative Exposure Therapy) on DNA breakage and repair. Thirty-eight individuals with PTSD were randomly assigned to either a treatment or a waitlist control condition. Follow-up was performed 4 months and 1 year after therapy. RESULTS: In study 1 we found higher levels of basal DNA breakage in individuals with PTSD and trauma-exposed subjects than in controls, indicating that traumatic stress is associated with DNA breakage. However, single-strand break repair was unimpaired in individuals with PTSD. In study 2, we found that psychotherapy reversed not only PTSD symptoms, but also DNA strand break accumulation. CONCLUSION: Our results show - for the first time in vivo - an association between traumatic stress and DNA breakage; they also demonstrate changes at the molecular level, i.e., the integrity of DNA, after psychotherapeutic interventions. PMID- 25116691 TI - Understanding and reducing the experimental variability of in vitro plasma protein binding measurements. AB - The experimental measurement of plasma protein binding is a useful in vitro Absorption Distribution Metabolism and Excretion(ADME) assay currently conducted in both screening and definitive early development candidate modes. The fraction unbound is utilized to calculate important pharmacokinetic (PK) parameters such as unbound clearance and unbound volume of distribution in animals that can be used to make human PK and dose predictions and estimate clinically relevant drug drug interaction potential. Although these types of assays have been executed for decades, a rigorous statistical analysis of sources of variability has not been conducted because of the tedious nature of the manual experiment. Automated conduct of the incubations using a 96-well equilibrium dialysis device as well as high-throughput liquid chromatography-mass spectrometry quantitation has now made this level of rigor accessible and useful. Sources of variability were assessed including well position, day-to-day, and site-to-site reproducibility. Optimal pH conditions were determined using a design of experiments method interrogating buffer strength, CO2 % and device preparation conditions. Variability was minimized by implementing an in-well control that is concurrently analyzed with new chemical entity analytes. Data acceptance criteria have been set for both the in-well control and the range of analyte variability, with a sliding scale tied to analyte-binding characteristics. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3302-3309, 2014. PMID- 25116692 TI - Analysis of STAT1 expression and biological activity reveals interferon-tau dependent STAT1-regulated SOCS genes in the bovine endometrium. AB - Signal transducer and activator of transcription (STAT) proteins are critical for the regulation of numerous biological processes. In cattle, microarray analyses identified STAT1 as a differentially expressed gene in the endometrium during the peri-implantation period. To gain new insights about STAT1 during the oestrous cycle and early pregnancy, we investigated STAT1 transcript and protein expression, as well as its biological activity in bovine tissue and cells of endometrial origin. Pregnancy increased STAT1 expression on Day 16, and protein and phosphorylation levels on Day 20. In cyclic and pregnant females, STAT1 was located in endometrial cells but not in the luminal epithelium at Day 20 of pregnancy. The expression of STAT1 during the oestrous cycle was not affected by progesterone supplementation. In vivo and in vitro, interferon-tau (IFNT) stimulated STAT1 mRNA expression, protein tyrosine phosphorylation and nuclear translocation. Using chromatin immunoprecipitation in IFNT-stimulated endometrial cells, we demonstrated an increase of STAT1 binding on interferon regulatory factor 1 (IRF1), cytokine-inducible SH2-containing protein (CISH), suppressor of cytokine signaling 1 and 3 (SOCS1, SOCS3) gene promoters consistent with the induction of their transcripts. Our data provide novel molecular insights into the biological functions of STAT1 in the various cells composing the endometrium during maternal pregnancy recognition and implantation. PMID- 25116695 TI - Trajectory study of energy transfer and unimolecular dissociation of highly excited allyl with argon. AB - The influence of rotational excitation on energy transfer in single collisions of allyl with argon and on allyl dissociation is investigated. About 90,000 classical scattering simulations are performed in order to determine collision induced changes in internal energy and in allyl rotational angular momentum. Dissociation is studied by means of about 50,000 additional trajectories evolved for the isolated allyl under three different conditions: allyl with no angular momentum (J = 0); allyl with the same microcanonically sampled initial conditions used for the collisions (J*); allyl evolving from the corresponding exit conditions after the collision. The potential energy surface is the sum of an intramolecular potential and an interaction one, and it has already been used in a previous work on allyl-argon scattering (Conte, R.; Houston, P. L.; Bowman, J. M. J. Phys. Chem. A 2013, 117, 14028-14041). Energy transfer data show that increased initial rotation favors, on average, increased relaxation of the excited molecule. The availability of a high-level intramolecular potential energy surface permits us to study the dependence of energy transfer on the type of starting allyl isomer. A turning point analysis is presented, and highly efficient collisions are detected. Collision-induced variations in the allyl rotational angular momentum may be quite large and are found to be distributed according to three regimes. The roles of rotational angular momentum, collision, and type of isomer on allyl unimolecular dissociation are considered by looking at dissociations times, kinetic energies of the fragments, and branching ratios. Generally, rotational angular momentum has a strong influence on the dissociation dynamics, while the single collision and the type of starting isomer are less influential. PMID- 25116694 TI - Costs associated with adverse events in patients with metastatic renal cell carcinoma. AB - OBJECTIVE: To estimate adverse event (AE) costs in patients receiving targeted therapies for the first line treatment of metastatic renal cell carcinoma (mRCC). METHODS: Retrospective study based on healthcare claims data for patients with mRCC, aged >=18 years, receiving first-line treatment with targeted therapies. AEs of interest comprised of abdominal pain, back pain, diarrhea, dyspnea, extremity pain, fatigue/asthenia, hand-foot syndrome, hypertension, lymphopenia, nausea/vomiting, neutropenia, proteinuria, and thrombocytopenia. Healthcare encounters for AEs were based on ICD-9-CM diagnosis/procedure codes on healthcare claims. AE costs were examined over a 30-day period, beginning with the date of first mention of AE, and were estimated based on the difference in total costs between patients with and without events. Drug costs of targeted agents were excluded from the analysis. Multivariate generalized linear models with a log link function and gamma response probability distribution were utilized to control for differences in baseline characteristics between patients with and without evidence of AEs. RESULTS: A total of 533 patients were included in this analysis: 418 patients with AE and 115 patients without AE. Baseline characteristics were generally similar between patients in the two groups. The GLM-based estimate of incremental 30-day post-event costs among patients with evidence of any adverse events was $9807 (95% CI = $4386-$22,947). For all types of adverse events examined, the estimated difference in costs between evented and non-evented patients was positive; the 95% CI did not include zero for all of the adverse events considered, except hypertension and proteinurea. Study limitations include errors of commission/omission, especially as they may affect case-finding methods that rely on ICD-9-CM diagnosis and procedure codes, as was the case in the current study. CONCLUSION: Costs associated with AEs of first-line targeted therapies are substantial in patients with mRCC. Efforts to prevent and/or better manage these events may reduce overall healthcare costs. PMID- 25116693 TI - Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from Turkey. AB - OBJECTIVE: To estimate the economic burden of multiple sclerosis (MS) in Turkey, including the relapses and disease severity, and to evaluate the quality-of-life of MS patients. METHODS: The Treatment Experience, Burden and Unmet Needs (TRIBUNE) study was a multi-national, cross-sectional, retrospective, burden-of illness survey. Total costs were calculated using unit costs derived from price lists or published literature, where relevant, and inflated to 2011 TL prices. RESULTS: A total of 295 MS patients (74% females) were included in the analysis. The population had a mean age of 36 years; 73% had the relapsing-remitting form. Mean Expanded Disability Status Scale (EDSS) score was 2.2. Twenty-two per cent of the MS patients required hospitalization in the past year and spent an average of 29.2 days/year in hospital. These values were 43% and 5.6 days for the outpatients, respectively. Total cost per patient/year was 18,700 TL (Turkish Lira). Total costs for patients with mild, moderate, and severe disability were 15,418 TL, 26,002 TL, and 44,208 TL per patient/year, respectively. The mean EuroQol 5D scores in the same groups were 0.73, 0.52, and 0.05, respectively. CONCLUSIONS: Multiple sclerosis imposes a significant economic burden on patients and society in Turkey. PMID- 25116685 TI - Antibacterial surface treatment for orthopaedic implants. AB - It is expected that the projected increased usage of implantable devices in medicine will result in a natural rise in the number of infections related to these cases. Some patients are unable to autonomously prevent formation of biofilm on implant surfaces. Suppression of the local peri-implant immune response is an important contributory factor. Substantial avascular scar tissue encountered during revision joint replacement surgery places these cases at an especially high risk of periprosthetic joint infection. A critical pathogenic event in the process of biofilm formation is bacterial adhesion. Prevention of biomaterial-associated infections should be concurrently focused on at least two targets: inhibition of biofilm formation and minimizing local immune response suppression. Current knowledge of antimicrobial surface treatments suitable for prevention of prosthetic joint infection is reviewed. Several surface treatment modalities have been proposed. Minimizing bacterial adhesion, biofilm formation inhibition, and bactericidal approaches are discussed. The ultimate anti infective surface should be "smart" and responsive to even the lowest bacterial load. While research in this field is promising, there appears to be a great discrepancy between proposed and clinically implemented strategies, and there is urgent need for translational science focusing on this topic. PMID- 25116696 TI - Play behavior of the golden-headed lion tamarin in Brazilian cocoa agroforests. AB - During play, primates may become more vulnerable to predation. Our goal was to examine the potential role of predation risk on the play behavior of 3 groups of golden-headed lion tamarin, Leontopithecus chrysomelas, in shaded cocoa agroforest (cabruca) of Southern Bahia, Brazil. We identified the preferred (and safer) locations on vertical strata during playtime and investigated if frequency and duration of play differed according to group size. All groups preferred to play on the lower levels of vertical strata, which may be perceived as either a safer environment or as a more suitable location for play due to the vegetation structure. The smallest group played less than the others, while the largest group played more and for longer periods. Our data suggest that predation risk can influence where play takes place as well as its frequency and length. PMID- 25116697 TI - Copper-catalyzed aerobic oxidative cleavage of C-C bonds in epoxides leading to aryl ketones. AB - A novel copper-catalyzed aerobic synthesis of ketones from epoxides via cleavage of C-C single bonds has been discovered. This reaction constitutes a new transformation from epoxides into ketones. PMID- 25116700 TI - Dynamic contrast-enhanced magnetic resonance imaging biomarkers in head and neck cancer: potential to guide treatment? A systematic review. AB - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) generates microvascular parameters from the tracer kinetic analysis of a series of MRI images obtained in under 15 min. DCE-MRI parameters are associated with tumour hypoxia, which is well-established as a cause of treatment failure in head and neck squamous cell carcinoma (HNSCC). A systematic review was conducted of prospective DCE-MRI parameter studies in HNSCC in the English language literature. Exclusion criteria were case reports and retrospective series. Six DCE-MRI marker studies in HNSCC met the inclusion criteria. Four studies contained 21-74 patients and two studies recruited 13 and 14 patients. In studies measuring the transfer coefficient (K(trans)), higher overall K(trans) or lower skewness of K(trans) were predictive of a good outcome following chemoradiation. DCE-MRI parameters have the potential to guide treatment in HNSCC. Progress in the field requires standardisation of methods, data sharing and large multi centre collaborative validation studies. PMID- 25116698 TI - Spectroscopic characterization and reactivity studies of a mononuclear nonheme Mn(III)-hydroperoxo complex. AB - We report the first example of a mononuclear nonheme manganese(III)-hydroperoxo complex derived from protonation of an isolated manganese(III)-peroxo complex bearing an N-tetramethylated cyclam (TMC) ligand, [Mn(III)(TMC)(OOH)](2+). The Mn(III)-hydroperoxo intermediate is characterized with various spectroscopic methods as well as with density functional theory (DFT) calculations, showing the binding of a hydroperoxide ligand in an end-on fashion. The Mn(III)-hydroperoxo species is a competent oxidant in oxygen atom transfer (OAT) reactions, such as the oxidation of sulfides. The electrophilic character of the Mn(III)-hydroperoxo complex is demonstrated unambiguously in the sulfoxidation of para-substituted thioanisoles. PMID- 25116702 TI - Highly porous NiCo2O4 Nanoflakes and nanobelts as anode materials for lithium-ion batteries with excellent rate capability. AB - Highly porous NiCo2O4 nanoflakes and nanobelts were synthesized by using a hydrothermal technique, followed by calcination of the NiCo2O4 precursors. The as synthesized materials were analyzed by scanning electron microscopy, X-ray diffraction, transmission electron microscopy, and Brunauer-Emmett-Teller methods. The NiCo2O4 nanoflakes and nanobelts were applied as anode materials for lithium-ion batteries. Owing to the unique porous structural features, the NiCo2O4 nanoflakes and nanobelts exhibited high specific capacities of 1033 and 1056 mA h g(-1), respectively, and good cycling stability and rate capability. These exceptional electrochemical performances could be ascribed to the remarkable structural feature with a high surface area and void spaces within the surface of nanoflakes and nanobelts, which provide large contact areas between electrolyte and active materials for electrolyte diffusion and cushion the volume variation during the lithium-ion insertion/extraction process. PMID- 25116701 TI - Pressure-induced magnetic crossover driven by hydrogen bonding in CuF2(H2O)2(3 chloropyridine). AB - Hydrogen bonding plays a foundational role in the life, earth, and chemical sciences, with its richness and strength depending on the situation. In molecular materials, these interactions determine assembly mechanisms, control superconductivity, and even permit magnetic exchange. In spite of its long standing importance, exquisite control of hydrogen bonding in molecule-based magnets has only been realized in limited form and remains as one of the major challenges. Here, we report the discovery that pressure can tune the dimensionality of hydrogen bonding networks in CuF2(H2O)2(3-chloropyridine) to induce magnetic switching. Specifically, we reveal how the development of O H...Cl exchange pathways under compression combined with an enhanced ab-plane hydrogen bonding network yields a three dimensional superexchange web between copper centers that triggers a reversible magnetic crossover. Similar pressure- and strain-driven crossover mechanisms involving coordinated motion of hydrogen bond networks may play out in other quantum magnets. PMID- 25116703 TI - Synthesis of 1,3,5,7-tetrakis(4-cyanatophenyl)adamantane and its microporous polycyanurate network for adsorption of organic vapors, hydrogen and carbon dioxide. AB - This report presents the synthesis of a tetraphenyladamantane-based microporous polycyanurate network with a BET surface area of 843 m(2) g(-1) and a pore size of 7.8 A. It uptakes 98.0 wt% benzene (298 K, P/P0 = 0.9), 1.49 wt% H2 (77 K/1 bar) and 12.8 wt% CO2 (273 K/1 bar) with CO2/N2 selectivity of up to 112. PMID- 25116704 TI - Adipocyte versus pituitary leptin in the regulation of pituitary hormones: somatotropes develop normally in the absence of circulating leptin. AB - Leptin is a cytokine produced by white fat cells, skeletal muscle, the placenta, and the pituitary gland among other tissues. Best known for its role in regulating appetite and energy expenditure, leptin is produced largely by and in proportion to white fat cells. Leptin is also important to the maintenance and function of the GH cells of the pituitary. This was shown when the deletion of leptin receptors on somatotropes caused decreased numbers of GH cells, decreased circulating GH, and adult-onset obesity. To determine the source of leptin most vital to GH cells and other pituitary cell types, we compared two different leptin knockout models with Cre-lox technology. The global Lep-null model is like the ob/ob mouse, whereby only the entire exon 3 is deleted. The selective adipocyte-Lep-null model lacks adipocyte leptin but retains pituitary leptin, allowing us to investigate the pituitary as a potential source of circulating leptin. Male and female mice lacking adipocyte leptin (Adipocyte-lep-null) did not produce any detectable circulating leptin and were infertile, suggesting that the pituitary does not contribute to serum levels. In the presence of only pituitary leptin, however, these same mutants were able to maintain somatotrope numbers and GH mRNA levels. Serum GH trended low, but values were not significant. However, hypothalamic GHRH mRNA was significantly reduced in these animals. Other serum hormone and pituitary mRNA differences were observed, some of which varied from previous results reported in ob/ob animals. Whereas pituitary leptin is capable of maintaining somatotrope numbers and GH mRNA production, the decreased hypothalamic GHRH mRNA and low (but not significant) serum GH levels indicate an important role for adipocyte leptin in the regulation of GH secretion in the mouse. Thus, normal GH secretion may require the coordinated actions of both adipocyte and pituitary leptin. PMID- 25116705 TI - A mollusk retinoic acid receptor (RAR) ortholog sheds light on the evolution of ligand binding. AB - Nuclear receptors are transcription factors that regulate networks of target genes in response to small molecules. There is a strong bias in our knowledge of these receptors because they were mainly characterized in classical model organisms, mostly vertebrates. Therefore, the evolutionary origins of specific ligand-receptor couples still remain elusive. Here we present the identification and characterization of a retinoic acid receptor (RAR) from the mollusk Nucella lapillus (NlRAR). We show that this receptor specifically binds to DNA response elements organized in direct repeats as a heterodimer with retinoid X receptor. Surprisingly, we also find that NlRAR does not bind all-trans retinoic acid or any other retinoid we tested. Furthermore, NlRAR is unable to activate the transcription of reporter genes in response to stimulation by retinoids and to recruit coactivators in the presence of these compounds. Three-dimensional modeling of the ligand-binding domain of NlRAR reveals an overall structure that is similar to vertebrate RARs. However, in the ligand-binding pocket (LBP) of the mollusk receptor, the alteration of several residues interacting with the ligand has apparently led to an overall decrease in the strength of the interaction with the ligand. Accordingly, mutations of NlRAR at key positions within the LBP generate receptors that are responsive to retinoids. Altogether our data suggest that, in mollusks, RAR has lost its affinity for all-trans retinoic acid, highlighting the evolutionary plasticity of its LBP. When put in an evolutionary context, our results reveal new structural and functional features of nuclear receptors validated by millions of years of evolution that were impossible to reveal in model organisms. PMID- 25116707 TI - Decidualization induces a secretome switch in perivascular niche cells of the human endometrium. AB - The endometrial perivascular microenvironment is rich in mesenchymal stem-like cells that express type 1 integral membrane protein Sushi domain containing 2 (SUSD2) but the role of these cells in the decidual transformation of this tissue in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to isolate perivascular (W5C5(+)) and nonperivascular (W5C5(-)) fibroblasts from mid luteal biopsies. We show that SUSD2 expression, and hence the ratio of W5C5(+):W5C5(-) cells, changes in culture depending on cell-cell contact and activation of the Notch signaling pathway. RNA sequencing revealed that cultures derived from W5C5(+) progenitor cells remain phenotypically distinct by the enrichment of novel and established endometrial perivascular signature genes. In an undifferentiated state, W5C5(+)-derived cells produced lower levels of various chemokines and inflammatory modulators when compared with their W5C5(-) counterparts. This divergence in secretomes was switched and became more pronounced upon decidualization, which transformed perivascular W5C5(+) cells into the dominant source of a range of chemokines and cytokines, including leukemia inhibitory factor and chemokine (C-C motif) ligand 7. Our findings suggest that the decidual response is spatially organized at the embryo-maternal interface with differentiating perivascular cells establishing distinct cytokine and chemokine profiles that could potentially direct trophoblast toward maternal vessels and govern local immune responses in pregnancy. PMID- 25116708 TI - Insulin action on GABA neurons is a critical regulator of energy balance but not fertility in mice. AB - Insulin signaling in the brain plays an important role in the central regulation of energy homeostasis and fertility, such that mice exhibiting brain-specific deletion of insulin receptors (InsRs) display a diet-sensitive obesogenic phenotype and hypothalamic hypogonadism. However, the specific neurons mediating insulin's central effects on fertility remain largely unidentified. The neurotransmitters gamma-aminobutyric acid (GABA) and glutamate are important modulators of fertility and energy homeostasis and are widely distributed in the hypothalamus. We therefore investigated whether insulin signaling via GABAergic or glutamatergic neurons plays an important role in the metabolic regulation of fertility. We used the Cre-loxP system to generate mice with a selective inactivation of the Insr gene from GABAergic (Vgat(+)) or glutamatergic (Vglut2(+)) cells by crossing Insr-flox mice with Vgat-Cre or Vglut2-Cre mice, respectively. Multiple reproductive and metabolic parameters were then compared between male and female Insr-flox/Vgat-Cre(+) (VgatIRKO), Insr-flox/Vglut2-Cre(+) (VglutIRKO), and Insr-flox/Cre-negative control (CON) mice. Female VgatIRKO mice exhibited a significant increase in adult body weight, abdominal fat mass, and fasting plasma insulin and leptin concentrations, but normal fasting glucose concentration and glucose tolerance compared with CON mice. Surprisingly, VgatIRKO and VglutIRKO mice exhibited normal reproductive maturation and function compared with CONs. No differences in the age of puberty onset, estrous cyclicity, or fertility were observed between VgatIRKO, VglutIRKO, and CON mice. However, male VgatIRKO mice exhibited significantly augmented LH concentration and a trend toward reduced seminal vesicle weight compared with CON mice, which may be indicative of primary hypogonadism. Our results therefore demonstrate that insulin signaling via GABAergic and glutamatergic cells is not required for fertility in mice, but show that GABAergic neurons encompass circuitry through which insulin acts to modulate energy homeostasis. PMID- 25116706 TI - GLP-1 receptor stimulation of the lateral parabrachial nucleus reduces food intake: neuroanatomical, electrophysiological, and behavioral evidence. AB - The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role in the normal maintenance of feeding behavior, because their loss leads to starvation. Viscerosensory stimuli result in neuronal activation of the PBN. However, the origin and neurochemical identity of the excitatory neuronal input to the PBN remain largely unexplored. Here, we hypothesize that hindbrain glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN, activation of which may lead to a reduction in feeding behavior. Our data, obtained from mice expressing the yellow fluorescent protein in GLP-1-producing neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of chow and palatable food and decreased body weight in rats. It also activated lPBN neurons, reflected by an increase in the number of c-Fos-positive cells in this region. Further support for an excitatory role of GLP-1 in the PBN is provided by electrophysiological studies showing a remarkable increase in firing of lPBN neurons after Exendin-4 application. We show that within the PBN, GLP-1R activation increased gene expression of 2 energy balance regulating peptides, calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application resulted in anorexia. Collectively, our molecular, anatomical, electrophysiological, pharmacological, and behavioral data provide evidence for a functional role of the GLP-1R for feeding control in the PBN. PMID- 25116709 TI - The American Board of Clinical Neuropsychology and American Academy of Clinical Neuropsychology: updated milestones 2005-2014. PMID- 25116710 TI - Brain alterations in paedophilia: a critical review. AB - Psychosocial and biological factors have been implicated in paedophilia, such as alterations in brain structure and function. The purpose of this paper is to review the expanding body of literature on this topic including brain abnormality case reports, as well as structural and functional neuroimaging studies. Case studies of men who have committed sexual offences against children implicate frontal and temporal abnormalities that may be associated with impaired impulse inhibition. Structural neuroimaging investigations show volume reductions in paedophilic men. Although the findings have been heterogeneous, smaller amygdala volume has been replicated repeatedly. Functional neuroimaging investigations demonstrate an overlap between paedophiles and teleiophiles during sexual arousal processing. While it is controversial among studies regarding group differences, reliable discrimination between paedophilic and teleiophilic men may be achieved using functional activation patterns. Nevertheless, the heterogeneous findings published so far suggest further research is necessary to disentangle the neurobiological mechanisms of paedophilic preference. A number of methodological confounds have been identified, which may account for the inconsistent results that could prove to be beneficial for future investigations. PMID- 25116711 TI - The role of P2X7 receptor in infectious inflammatory diseases and the influence of ectonucleotidases. AB - The purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is ubiquitously expressed in almost all tissues and organs of the body with the highest distribution in the immune cells of monocyte-macrophage origin. Classically, P2X7 receptor is involved in apoptotic cell death, and it is well known that extracellular ATP ligation to this purinergic receptor serves as an important secondary stimulus, which is also considered as danger signal for the interleukin (IL)-1beta cleavage and secretion from pro-inflammatory cells. More recently, however, there has been substantial evidence of additional roles for the P2X7 receptor, both in innate immune response and as an adaptive link, including T cell activation in a chronic state of inflammation. Also, compelling evidences have revealed an important role for ectonucleotidases as ATP-consuming enzymes in the control and fine-tuning of P2X7 function by regulating the time, concentration, and availability of ATP during infection-driven inflammation. This review focuses on the current evidences for P2X7 receptor involvement in the initial stages of inflammation, as well as for its role in acute and chronic stages of infection. Here, we also highlight the role of ectonucleotidase family in the control of P2X7 function, including the initial and resolution phases of inflammation. PMID- 25116712 TI - Proton pump inhibitors and risk for Clostridium difficile associated diarrhea. AB - Increased incidence of Clostridium difficile infection (CDI) among in-patients is associated with significant increased mortality, morbidity, and stay in the hospitals. This has occurred despite heightened awareness of the risks of broad spectrum antibiotics, overall reduction in antibiotic use and increased focus on hospital hygiene. So though the main risk factor for CDI is use of broad-spectrum antibiotics, the use of proton pump inhibitors (PPIs) as a novel potential contributor has been implicated, because of their ability to substantially reduce gastric acid secretion which is an important host defense mechanism in suppressing the ingested C. difficile or its spores. Antibiotic disruption of the normal intestinal flora and reduced gastric acidity have been suggested as the risk factors for C. difficile-associated diarrhea (CDAD). Based on such assumptions the use of PPIs may be associated with an increased risk of CDAD. While a definite association between PPI use and CDAD has not yet been confirmed, the possibility and such an association however cannot be ruled out at present. Thus among the identified risk factors, the use of PPI is important, previously unrecognized and modifiable risk factors whose use should be carefully evaluated among hospital in-patients receiving antibiotics, especially in those with a diagnosis of C. difficile diarrhea. PMID- 25116713 TI - Systematic review of the surgery-first approach in orthognathic surgery. AB - The surgery-first approach in orthognathic surgery has recently created a broader interest in completely eliminating time-consuming preoperative orthodontic treatment. Available evidence on the surgery-first approach should be appraised to support its use in orthognathic surgery. A MEDLINE search using the keywords "surgery first" and "orthognathic surgery" was conducted to select studies using the surgery-first approach. We also manually searched the reference list of the selected keywords to include articles not selected by the MEDLINE search. The search identified 18 articles related to the surgery-first approach. There was no randomized controlled clinical trial. Four papers were excluded as the content was only personal opinion or basic scientific research. Three studies were retrospective cohort studies in nature. The other 11 studies were case reports. For skeletal Class III surgical correction, the final long-term outcomes for maxillofacial and dental relationship were not significantly different between the surgery-first approach and the orthodontics-first approach in transverse (e.g., intercanine or intermolar width) dimension, vertical (e.g., anterior open bite, lower anterior facial height) dimension, and sagittal (e.g., anterior posterior position of pogonion and lower incisors) dimension. Total treatment duration was substantially shorter in cases of surgery-first approach use. In conclusion, most published studies related to the surgery-first approach were mainly on orthognathic correction of skeletal Class III malocclusion. Both the surgery-first approach and orthodontics-first approach had similar long-term outcomes in dentofacial relationship. However, the surgery-first approach had shorter treatment time. PMID- 25116714 TI - PPARgamma ligand ciglitazone inhibits TNFalpha-induced ICAM-1 in human airway smooth muscle cells. AB - BACKGROUND: Modification of human airway smooth muscle (ASM) function by proinflammatory cytokines has been regarded as a potential mechanism underlying bronchial hyperresponsiveness in asthma. Human ASM cells express intercellular adhesion molecule (ICAM)-1 in response to cytokines. Synthetic ligands for peroxisome proliferator-activated receptor (PPAR)gamma reportedly possess anti inflammatory and immunomodulatory properties. In this study, we examined whether ciglitazone, a synthetic PPARgamma ligand, can modulate the basal and tumor necrosis factor (TNF)alpha-induced ICAM1 gene expression in human ASM cells. METHODS: Human ASM cells were treated with TNFalpha. ICAM-1 expression was assessed by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. PPARgamma activity was inhibited by target-specific small interfering (si) RNA targeting PPARgamma and GW9662, a PPARgamma antagonist. Activity of nuclear factor (NF)-kappaB was assessed by using immunoblot analysis, immune-confocal images, and electrophoretic mobility shift assay (EMSA). RESULTS: By flow cytometry, ciglitazone alone had no effect on ICAM-1 expression in ASM cells, but inhibited ICAM-1 expression in response to TNFalpha (10 ng/ml) in a dose-dependent manner (1-10 MUM). It also inhibited TNFalpha-induced ICAM1 gene expression by RT-PCR analysis. Knockdown of PPARgamma gene by target-specific siRNA targeting PPARgamma enhanced ICAM-1 expression and the inhibitory effect of ciglitazone on TNFalpha-induced ICAM-1 expression was reversed by PPARgamma siRNA and GW9662. SN-50 (10 MUg/ml), an inhibitor for nuclear translocation of NF kappaB, inhibited TNFalpha-induced ICAM-1 expression. Ciglitazone did not prevent TNFalpha-induced degradation of the cytosolic inhibitor of NF-kappaB (IkappaB), but inhibited the nuclear translocation of p65 induced by TNFalpha and suppressed the NF-kappaB/DNA binding activity. CONCLUSION: These findings suggest that ciglitazone inhibits TNFalpha-induced ICAM1 gene expression in human ASM cells through the ligand-dependent PPARgamma activation and NF-kappaB-dependent pathway. PMID- 25116715 TI - Thromboprophylaxis after minimally invasive total knee arthroplasty: a comparison of rivaroxaban and enoxaparin. AB - BACKGROUND: Total knee arthroplasty (TKA) carries a substantial rate of venous thromboembolism (VTE). The blood-saving of effect of tranexamic acid (TEA) in TKA using enoxaparin for thromboprophylaxis has been well known. However, the routine use of chemoprophylaxis in TKA remains controversial because of postoperative bleeding complications. Therefore, the purpose of this study was to retrospectively compare the incidence of VTE, and postoperative blood loss and wound-related complications in minimally invasive (MIS)-TKA patients who received rivaroxaban or enoxaparin prophylaxis. METHODS: A total of 113 patients who underwent primary unilateral MIS-TKA between 2009 and 2012 were studied. Of these, 61 patients (study group) received rivaroxaban prophylaxis between 2011 and 2012 and a control group of 52 patients received enoxaparin prophylaxis between 2009 and 2010. All patients received one intraoperative injection of TEA (10 mg/kg). We compared the changes in hemoglobin (Hb) level, postoperative drainage amount, total blood loss, transfusion rate, and incidence of postoperative wound complications and VTE between the two groups. RESULTS: No differences in postoperative Hb levels, blood drainage amount, total blood loss, and transfusion rate were observed between the two groups. No deep-vein thrombosis of the leg or pulmonary embolism was noted in both groups. There were no major wound complications including hematoma and infection requiring surgical intervention for open irrigation or debridement. CONCLUSIONS: Our retrospective study demonstrated a low rate of VTE in MIS-TKA patients who received rivaroxaban or enoxaparin when TEA was used for bleeding prophylaxis. No increased perioperative bleeding or postoperative wound-related complications were observed in the rivaroxaban group compared with the enoxaparin group. PMID- 25116716 TI - Effects of neuromuscular electrical stimulation on arterial hemodynamic properties and body composition in paretic upper extremities of patients with subacute stroke. AB - BACKGROUND: Neuromuscular electric stimulation (NMES) induces repeated muscular contraction, possibly promoting the perfusion/oxygenation of the regional tissues. It remains unclear how NMES influences vascular hemodynamic property and segmental fluid distribution/composition in paretic extremities of hemiplegic patients. METHODS: Eleven hemiplegic patients aged 62.6 +/- 12.5 years in the subacute stage of stroke received NMES for paretic wrist extensor and flexor muscles 30 min daily, 5 days per week for 4 weeks. The non-paretic upper extremities (NPUE) that did not receive NMES served as control. Distribution of fluid to intra/extracellular milieu and arterial hemodynamic properties were determined by using the multi-frequency bioelectrical impedance and pulse wave analysis, respectively. RESULTS: Compared with NPUE without NMES, paretic upper extremity (PUE) with NMES revealed a significantly less decrease in arterial blood flow, impedance quotient, slope quotient, and less increase in crest width and crest time of arterial pulse wave. NMES for 4 weeks increased body cell mass in PUE. Furthermore, NPUE without NMES reduced intracellular water, whereas PUE with NMES retarded loss of intracellular water after stroke. CONCLUSION: NMES therapy increases body cell mass, attenuates reduction of intracellular water, and alleviates arterial hemodynamic disturbance in PUE in subacute stroke. However, stroke-related physical deconditioning may negatively regulate body composition and impair hemodynamic function in NPUE. PMID- 25116717 TI - Extended shelf life of random donor platelets stored for 7 days in platelet additive solution at different temperatures. AB - BACKGROUND: Platelets are routinely stored in plasma for 5 days at an average temperature of 22 degrees C. In the present study, the shelf life of random donor platelets was extended by storing for 7 days with and without additive solution at temperatures of 22 degrees C, 18 degrees C, and 16 degrees C. METHODS: Random donor platelets were stored in 100% plasma and 20%/80% platelet additive solution. The data were compared using paired "t"- test. The confidence limit was kept at 95%, hence a "p" < 0.05 was considered to be statistically significant. RESULTS: Out of total 150 samples, 148 samples were analyzed and 2 were discarded due to the bacterial contamination on day 7 at 22 degrees C without platelet additive solution. A significant difference in platelet count, platelet factor 3 (PF 3), glucose, lactate dehydrogenase (LDH), and platelet aggregation was observed on day 7 (p < 0.001) at 16 degrees C in without platelet additive solution. In platelet additive solution, the mean values of platelet count, platelet distribution width (PDW), LDH, and pH showed no significant difference on day 7 at 22 degrees C, 18 degrees C, and 16 degrees C. Only significant differences were observed in the levels of mean platelet volume (MPV), PF 3, glucose, and platelet aggregation on day 7 (p < 0.001) at 16 degrees C of the storage period. CONCLUSION: Random donor platelets functions are better maintained in platelet additive solution as compared to plasma at a lower temperature of 18 degrees C but not at 16 degrees C, on the 7 th day. PMID- 25116719 TI - Effect of environmental enrichment exposure on neuronal morphology of streptozotocin-induced diabetic and stressed rat hippocampus. AB - BACKGROUND: Environmental enrichment (EE) exposure is known to influence the structural changes in the neuronal network of hippocampus. In the present study, we evaluated the effects of EE exposure on the streptozotocin (STZ)-induced diabetic and stressed rat hippocampus. METHODS: Male albino rats of Wistar strain (4-5 weeks old) were grouped into normal control (NC), vehicle control (VC), diabetes (DI), diabetes + stress (DI + S), diabetes + EE (DI + E), and diabetes + stress + EE (DI + S + E) groups (n = 8 in each group). Rats were exposed to stress and EE after inducing diabetes with STZ (40 mg/kg). Rats were sacrificed on Day 30 and brain sections were processed for cresyl violet staining to quantify the number of surviving neurons in the CA1, CA3, and dentate hilus (DH) regions of hippocampus. RESULTS: A significant (p < 0.001) decrease in the number of survived neurons was noticed in DI (CA1, 34.06 +/- 3.2; CA3, 36.1 +/- 3.62; DH, 9.83 +/- 2.02) as well as DI + S (CA1, 14.03 +/- 3.12; CA3, 20.27 +/- 4.09; DH, 6.4 +/- 1.21) group rats compared to NC rats (CA1, 53.64 +/- 2.96; CA3, 62.1 +/- 3.34; DH, 21.11 +/- 1.03). A significant (p < 0.001) increase in the number of survived neurons was observed in DI + E (CA1, 42.3 +/- 3.66; CA3, 46.73 +/- 4.74; DH, 17.03 +/- 2.19) and DI + S + E (CA1, 29.69 +/- 4.47; CA3, 36.73 +/- 3.89; DH, 12.23 +/- 2.36) group rats compared to DI and DI + S groups, respectively. CONCLUSIONS: EE exposure significantly reduced the amount of neuronal damage caused by complications of diabetes and stress to the neurons of hippocampus. PMID- 25116718 TI - Anti-adhesive effect of hyaluronate in a rabbit laminectomy model. AB - BACKGROUND: Postlaminectomy dural adhesion is a common cause of recurrent symptoms. Hyaluronic acid-based gel has been reported to reduce the incidence of postoperative adhesion in the peritoneal cavity; however, its effect on preventing postoperative scar formation at laminectomy sites is not yet known. The purpose of this study was to evaluate the anti-adhesive effect of hyaluronic acid-based gelatin after laminectomy, using a rabbit model. METHODS: Twelve adult New Zealand rabbits underwent two-level lumbar laminectomy, and were randomly assigned to one of two groups of six rabbits each. The treatment group received hyaluronic acid-based gelatin treatment and the control group was untreated. Rabbits were sacrificed 8 weeks after treatment. Peel-off testing and histological analysis were performed to assess the tenacity and the extent of adhesion formation. RESULTS: No significant difference was observed in the neurologic performance between the two groups. The tenacity in the treatment group was significantly reduced compared to that of the control group (3.17 +/- 0.75 vs. 4.33 +/- 0.52, respectively; p = 0.016). Histological analysis showed significantly less scar tissue formation in the treatment group, with a larger subarachnoid space and greater distance between the dura and scar tissues. The amount of fibroblast cells also was significantly smaller in the treatment group than in the control group (3078 +/- 313.68 vs. 3742 +/- 455.65, respectively; p = 0.042). CONCLUSIONS: No serious adverse events were reported, and no difference was found in the incidence of complications between the treatment and control groups. The findings suggested that hyaluronic acid-based gelatin may be effective for preventing postlaminectomy dural adhesion in rabbits. PMID- 25116720 TI - Fetal magnetic resonance imaging of normal spinal cord: evaluating cord visualization and conus medullaris position by T2-weighted sequences. AB - BACKGROUND: Prenatal magnetic resonance (MR) imaging demonstration of the normal spinal cord and the conus medullaris location has not been well studied. We compared balanced fast field echo (bFFE) with single-shot turbo spin-echo (SSh TSE) MR sequences for visualizing the normal spinal cord and position of conus medullaris in fetuses. METHODS: This retrospective study was approved by the Institutional Review Board of Chang Gung Medical Foundation. We reviewed the MR images of 141 fetuses aged between 16 and 39 gestational weeks, to determine the position of the conus and visualize the spinal cord by using a signal intensity ratio of cerebral spinal fluid (CSF) to the spinal cord. RESULTS: Of the 75 subjects having normal spinal cord and being examined by both bFFE and SSh-TSE studies, the signal intensity ratio of CSF/cord was greater on bFFE images (2.18 +/- 0.53) than that on SSh-TSE images (1.21 +/- 0.13) (p < 0.05). The conus level identified in the 50 subjects, in whom the lumbosacral spine was appropriately imaged, was located from L1 to L5 levels. The ascendance of the conus correlated moderately with gestational age. CONCLUSIONS: With greater signal contrast ratio of CSF to spinal cord, bFFE sequence, when compared with SSh-TSE sequence, provides better visualization of normal spinal cord. The fetal conus medullaris ascends from L5 to L1 levels as the gestational age increases. PMID- 25116721 TI - Co-infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and bone marrow derived hematopoietic stem cells, a viable therapy for post-traumatic brachial plexus injury: a case report. AB - Stem cell therapy is emerging as a viable approach in regenerative medicine. A 31 year-old male with brachial plexus injury had complete sensory-motor loss since 16 years with right pseudo-meningocele at C5-D1 levels and extra-spinal extension up to C7-D1, with avulsion on magnetic resonance imaging and irreversible damage. We generated adipose tissue derived neuronal differentiated mesenchymal stem cells (N-AD-MSC) and bone marrow derived hematopoietic stem cells (HSC-BM). Neuronal stem cells expressed beta-3 tubulin and glial fibrillary acid protein which was confirmed on immunofluorescence. On day 14, 2.8 ml stem cell inoculum was infused under local anesthesia in right brachial plexus sheath by brachial block technique under ultrasonography guidance with a 1.5-inch-long 23 gauge needle. Nucleated cell count was 2 * 10 4 /MUl, CD34+ was 0.06%, and CD45-/90+ and CD45-/73+ were 41.63% and 20.36%, respectively. No untoward effects were noted. He has sustained recovery with re-innervation over a follow-up of 4 years documented on electromyography-nerve conduction velocity study. PMID- 25116722 TI - Conformational and H-bonding preferences for facile racemate crystallization of ribose. AB - Recalcitrant crystallization and syrup formation are frequent features of natural sugars. This is the case of D-ribose, yielding low-quality crystals of mixed alpha- and beta-pyranose anomers. However, large crystals of DL-ribose can be grown easily. The crystal structures of stable D-ribose forms I and II as well as DL-form II have been analyzed in terms of their compatibility with the molecular aggregation. The comparison of the potential energy of all conformers and their OH...O hydrogen-bonding patterns is consistent with the preferential racemate crystallization in terms of departures from the optimized isolated ribose molecule and its directional interactions. This analysis is aimed at rationalizing the interplay between the molecular structure and spontaneous crystallization of chiral compounds. PMID- 25116723 TI - Nickelalactones with an allyl subunit - the effect of penta-coordination on structures and stability. AB - A series of allyl modified nickelalactone derivatives of the general formula [(L)nNi{CH2C(CH3)C(CH3)CH2COO}] was synthesized via ligand exchange reactions in order to investigate the influence of the neutral ligand L on the structure and stability of these complexes. While the square planar 1,8 diazabicyclo[5,4,0]undec-7-ene ligated derivative 1 is stable in the solid state and in solution at ambient temperature, the use of the chelating ligands 6 diphenylphosphino-1,8-diazabicyclo[5.4.0]undec-7-ene, 1,1 bis(dicyclohexylphosphino)methane and 1,2-bis(dicyclohexylphosphino)ethane (dcpe) led to square pyramidal derivatives 2, 4, and 5 with a novel ligand arrangement. In solution, these derivatives are fluxional and show increasing tendencies in the order 2 < 4 < 5 to decouple the nickelalactone moiety to 2,3 dimethylbutadiene (dmbd), CO2 and zero-valent nickel complexes. During the investigation of 5, the tetrahedral complex [(dcpe)2Ni] (6) and the trigonal planar derivative [(dcpe)Ni(dmbd)] (7) were observed as predominant decomposition products. In the case of the application of 1,1-bis(diphenylphosphino)methane as a neutral ligand, a dinuclear nickelalactone species [(MU dppm)(Ni{CH2C(CH3)C(CH3)CH2COO})2] (3) was isolated in which the two nickel atoms realize different coordination geometries (SP-4 and SPY-5) in the solid state. The complexes were characterized by NMR techniques, single crystal X-ray diffraction measurements and infrared spectroscopy. PMID- 25116724 TI - Autologous haematopoietic stem cell transplantation reduces abnormalities in the expression of immune genes in multiple sclerosis. AB - Autologous haematopoietic stem-cell transplantation (AHSCT) has been experimented as a treatment in patients affected by severe forms of multiple sclerosis (MS) who failed to respond to standard immunotherapy. The rationale of AHSCT is to 'reboot' the immune system and reconstitute a new adaptive immunity. The aim of our study was to identify, through a robust and unbiased transcriptomic analysis, any changes of gene expression in T-cells potentially underlying the treatment effect in patients who underwent non-myeloablative AHSCT for treatment of MS. We evaluated by microarray DNA-chip technology the gene expression of peripheral CD4+ and CD8+ T-cell subsets sorted from patients with MS patients before AHSCT, at 6 months, 1 year and 2 years after AHSCT and from healthy control subjects. Hierarchical clustering analysis revealed that reconstituted CD8+ T-cells of MS patients at 2 years post-transplantation, aggregated together with healthy controls, suggesting a normalization of gene expression in CD8+ cells post therapy. When we compared the gene expression in MS patients before and after therapy, we detected a large number of differentially expressed genes (DEG) in both CD8+ and CD4+ T-cell subsets at all time points after transplantation. We catalogued the biological function of DEG and we selected 27 genes known to be involved in immune function for accurate quantification of gene expression by real-time PCR. The analysis confirmed and extended with quantitative data, a number of significant changes in both the CD4+ and CD8+ T-cells subsets from MS post-transplant. Notably, CD8+ T-cells revealed more extensive changes in the expression of genes involved in effector immune responses. PMID- 25116725 TI - Recovery of flavonoids from orange press liquor by an integrated membrane process. AB - Orange press liquor is a by-product generated by the citrus processing industry containing huge amounts of natural phenolic compounds with recognized antioxidant activity. In this work, an integrated membrane process for the recovery of flavonoids from orange press liquors was investigated on a laboratory scale. The liquor was previously clarified by ultrafiltration (UF) in selected operating conditions by using hollow fiber polysulfone membranes. Then, the clarified liquor with a total soluble solids (TSS) content of 10 g.100 g-1 was pre concentrated by nanofiltration (NF) up to 32 g TSS 100 g-1 by using a polyethersulfone spiral-wound membrane. A final concentration step, up to 47 g TSS 100 g-1, was performed by using an osmotic distillation (OD) apparatus equipped with polypropylene hollow fiber membranes. Suspended solids were completely removed in the UF step producing a clarified liquor containing most part of the flavonoids of the original press liquor due to the low rejection of the UF membrane towards these compounds. Flavanones and anthocyanins were highly rejected by the NF membrane, producing a permeate stream with a TSS content of 4.5 g.100 g-1. An increasing of both the flavanones and anthocyanins concentration was observed in the NF retentate by increasing the volume reduction factor (VRF). The final concentration of flavonoids by OD produced a concentrated solution of interest for nutraceutical and pharmaceutical applications. PMID- 25116727 TI - Optimising retention through multiple study opportunities over days: The benefit of an expanding schedule of repetitions. AB - Few studies have investigated how scheduling repeated studies of the same material over several days influences its subsequent retention. The study-phase retrieval hypothesis predicts that, under these circumstances, expanding intervals between repetitions will promote the greatest likelihood that the participant will be reminded of previous occurrences of the item, thus leading to a benefit for subsequent recall. In the present article, participants studied vocabulary pairs that were repeated according to one of three schedules. In the expanding schedule, pairs were presented on days 1, 2 and 13; in the uniform schedule, on days 1, 7 and 13; and in the contracting schedule, on days 1, 12 and 13. Cued-recall was assessed after a retention interval (RI) of 2, 6 or 13 days. Consistent with predictions, the expanding schedule generally led to better performance than the other schedules. However, further analyses suggested that the benefit of an expanding schedule may be greater when the RI is longer. PMID- 25116728 TI - Retraction: common occurrence of ceftriaxone-resistant, methicillin-sensitive Staphylococcus aureus at a Community Teaching Hospital. PMID- 25116731 TI - New cyanopyridone based luminescent liquid crystalline materials: synthesis and characterization. AB - A new series of 4-(3,4-bis(akyloxy)phenyl)-6-(4-((1-(4-cyano- or 4-nitro-benzyl) 1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles carrying terminal di-alkoxy chain lengths (viz. octyloxy, decyloxy, dodecyloxy, tetradecyloxy and hexadodecyloxy) as well as terminal polar groups -CN or -NO2 have been designed and synthesized successfully as luminescent mesogens. Their thermotropic behaviors have been studied by means of differential scanning calorimetry and polarized optical microscopy. The supramolecular organizations in them were explored by the temperature dependent X-ray diffraction method and their photophysical properties were investigated using UV-visible and fluorescence spectral methods. The mesogenic study reveals that the presence of hydrogen bonds, as well as dimerization between the molecules, is mainly responsible for the formation of the ambient temperature hexagonal columnar phase (Colh) in the new molecules. Their photophysical study indicates that the compounds exhibit a strong absorption band at ~370 nm and a blue emission band at ~466 nm with good quantum yields of ~0.62 when compared to quinine sulphate (Phif = 0.54) in chloroform. Also, the compounds show a slightly red shift in the absorption band with increased solvent polarity. In liquid crystalline films, they display a bathochromic shift in the emission band because of the intimate overlap of molecular cores in the hexagonal columnar phase. PMID- 25116729 TI - A 70-year-old kidney transplant recipient presenting with persistent leg cellulitis. PMID- 25116726 TI - Decreased occipital cortical glutamate levels in response to successful cognitive behavioral therapy and pharmacotherapy for major depressive disorder. AB - BACKGROUND: Previous studies have demonstrated that antidepressant medication and electroconvulsive therapy increase occipital cortical gamma-aminobutyric acid (GABA) in major depressive disorder (MDD), but a small pilot study failed to show a similar effect of cognitive-behavioral therapy (CBT) on occipital GABA. In light of these findings we sought to determine if baseline GABA levels predict treatment response and to broaden the analysis to other metabolites and neurotransmitters in this larger study. METHODS: A total of 40 MDD outpatients received baseline proton magnetic resonance spectroscopy (1H-MRS), and 30 subjects completed both pre- and post-CBT 1H-MRS; 9 CBT nonresponders completed an open-label medication phase followed by an additional/3rd 1H-MRS. The magnitude of treatment response was correlated with occipital amino acid neurotransmitter levels. RESULTS: Baseline GABA did not predict treatment outcome. Furthermore, there was no significant effect of CBT on GABA levels. However, we found a significant group * time interaction (F1, 28 = 6.30, p = 0.02), demonstrating reduced glutamate in CBT responders, with no significant glutamate change in CBT nonresponders. CONCLUSIONS: These findings corroborate the lack of effect of successful CBT on occipital cortical GABA levels in a larger sample. A reduction in glutamate levels following treatment, on the other hand, correlated with successful CBT and antidepressant medication response. Based on this finding and other reports, decreased occipital glutamate may be an antidepressant response biomarker. Healthy control comparator and nonintervention groups may shed light on the sensitivity and specificity of these results. PMID- 25116732 TI - Collisional energy transfer in highly excited molecules. AB - The excitation/de-excitation step in the Lindemann mechanism is investigated in detail using model development and classical trajectory studies based on a realistic potential energy surface. The model, based on a soft-sphere/line-of centers approach and using elements of Landau-Teller theory and phase space theory, correctly predicts most aspects of the joint probability distribution P(DeltaE,DeltaJ) for the collisional excitation and de-excitation process in the argon-allyl system. The classical trajectories both confirm the validity of the model and provide insight into the energy transfer. The potential employed was based on a previously available ab initio intramolecular potential for the allyl fit to 97418 allyl electronic energies and an intermolecular potential fit to 286 Ar-allyl energies. Intramolecular energies were calculated at the CCSD(T)/AVTZ level of theory, while intermolecular energies were calculated at the MP2/AVTZ level of theory. Trajectories were calculated for each of four starting allyl isomers and for an initial rotational level of Ji = 0 as well as for Ji taken from a microcanonical distribution. Despite a dissimilarity in Ar-allyl potentials for fixed Ar-allyl geometries, energy transfer properties starting from four different isomers were found to be remarkably alike. A contributing factor appears to be that the orientation-averaged potentials are almost identical. The model we have developed suggests that most hydrocarbons should have similar energy transfer properties, scaled by differences in the potential offset of the atom-hydrogen interaction. Available data corroborate this suggestion. PMID- 25116733 TI - Activation of peroxisome proliferator-activated receptor delta inhibits angiotensin II-induced activation of matrix metalloproteinase-2 in vascular smooth muscle cells. AB - We investigated the role of peroxisome proliferator-activated receptor (PPAR) delta on angiotensin (Ang) II-induced activation of matrix metalloproteinase (MMP)-2 in vascular smooth muscle cells (VSMCs). Activation of PPARdelta by GW501516, a specific ligand for PPARdelta, attenuated Ang II-induced activation of MMP-2 in a concentration-dependent manner. GW501516 also inhibited the generation of reactive oxygen species in VSMCs treated with Ang II. A marked increase in the mRNA levels of tissue inhibitor of metalloproteinase (TIMP)-2 and -3, endogenous antagonists of MMPs, was also observed in GW501516-treated VSMCs. These effects were markedly reduced in the presence of siRNAs against PPARdelta, indicating that the effects of GW501516 are PPARdelta dependent. Among the protein kinases inhibited by GW501516, suppression of phosphatidylinositol 3 kinase/Akt signaling was shown to have the greatest effect on activation of MMP-2 in VSMCs treated with Ang II. Concomitantly, GW501516-mediated inhibition of MMP 2 activation in VSMCs treated with Ang II was associated with the suppression of cell migration to levels approaching those in cells not exposed to Ang II. Thus, activation of PPARdelta confers resistance to Ang II-induced degradation of the extracellular matrix by upregulating expression of its endogenous inhibitor TIMP and thereby modulating cellular responses to Ang II in vascular cells. PMID- 25116734 TI - Hydrodehalogenation of alkyl iodides with base-mediated hydrogenation and catalytic transfer hydrogenation: application to the asymmetric synthesis of N protected alpha-methylamines. AB - We report a very mild synthesis of N-protected alpha-methylamines from the corresponding amino acids. Carboxyl groups of amino acids are reduced to iodomethyl groups via hydroxymethyl intermediates. Reductive deiodination to methyl groups is achieved by hydrogenation or catalytic transfer hydrogenation under alkaline conditions. Basic hydrodehalogenation is selective for the iodomethyl group over hydrogenolysis-labile protecting groups, such as benzyloxycarbonyl, benzyl ester, benzyl ether, and 9-fluorenyloxymethyl, thus allowing the conversion of virtually any protected amino acid into the corresponding N-protected alpha-methylamine. PMID- 25116735 TI - Alternative forms of Y-box binding protein 1 and YB-1 mRNA. AB - The multifunctional eukaryotic protein YB-1 (Y-box binding protein 1) plays a role in DNA reparation, transcription regulation, splicing, and mRNA translation, thereby participating in many crucial events in cells. Its effect is dependent mostly on its amount, and hence, on regulation of its synthesis. Published data on regulation of synthesis of YB-1 mediated by its mRNA 5' UTR, and specifically on the 5' UTR length and the presence of TOP-like motifs in this region, are contradictory. Here we report that 5' UTRs of major forms of human, rabbit, and mouse YB-1 mRNAs are about 140 nucleotides long and contain no TOP-like motifs mentioned in the literature. Also, we have found that YB-1 specifically interacts with the 5' UTR of its own mRNA within a region of about 100 nucleotides upstream from the start codon. Apart from YB-1, translation of YB-1 mRNA in a cell free system gives an additional product with an extended N-terminus and lower electrophoretic mobility. The start codon for synthesis of the additional product is AUC at position -(60-58) of the same open reading frame as that for the major product. Also, in the cell there is an alternative YB-1 mRNA with exon 1 replaced by a part of intron 1; YB-1 synthesized in vitro from this mRNA contains, instead of its N-terminal A/P domain, 10-11 amino acids encoded by intron 1. PMID- 25116737 TI - Three-dimensional hierarchically porous all-carbon foams for supercapacitor. AB - Three-dimensional hierarchically porous carbon-CNT-graphene ternary all-carbon foams (3D-HPCFs) with 3D macro- and mesoporous structures, a high specific surface area (1286 m(2) g(-1)), large bimodal mesopores (5.1 and 2.7 nm), and excellent conductivity have been fabricated through multicomponent surface self assembly of graphene oxide (GO)-dispersed pristine CNTs (GOCs) supported on a commercial sponge. The commercial sponge with a 3D interconnected macroporous framework not only is used as a support for GOCs and subsequently multicomponent self-assembly but also serves as a 3D scaffold to buffer electrolytes to reduce ion transport resistance and ion diffusion distance, while the GO acts as "surfactant" to directly disperse pristine CNTs, preserving the excellent electronic structure of pristine CNTs, and the CNTs also prevent the aggregation of graphene as well as improve the whole conductivity. Benefiting from the aforementioned characteristics, the 3D-HPCFs-based supercapacitors show outstanding specific capacitance, high rate capability, and excellent cycling stability, making them potentially promising for high-performance energy storage devices. PMID- 25116736 TI - Genome-wide genotype and sequence-based reconstruction of the 140,000 year history of modern human ancestry. AB - We investigated ancestry of 3,528 modern humans from 163 samples. We identified 19 ancestral components, with 94.4% of individuals showing mixed ancestry. After using whole genome sequences to correct for ascertainment biases in genome-wide genotype data, we dated the oldest divergence event to 140,000 years ago. We detected an Out-of-Africa migration 100,000-87,000 years ago, leading to peoples of the Americas, east and north Asia, and Oceania, followed by another migration 61,000-44,000 years ago, leading to peoples of the Caucasus, Europe, the Middle East, and south Asia. We dated eight divergence events to 33,000-20,000 years ago, coincident with the Last Glacial Maximum. We refined understanding of the ancestry of several ethno-linguistic groups, including African Americans, Ethiopians, the Kalash, Latin Americans, Mozabites, Pygmies, and Uygurs, as well as the CEU sample. Ubiquity of mixed ancestry emphasizes the importance of accounting for ancestry in history, forensics, and health. PMID- 25116738 TI - Comment on Osteocytes: masters orchestrators of bone. PMID- 25116740 TI - Molecular modeling of potential anticancer agents from African medicinal plants. AB - Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or in silico virtual screening methods are often used in lead/hit discovery protocols. In this study, the "drug-likeness" of ~400 compounds from African medicinal plants that have shown in vitro and/or in vivo anticancer, cytotoxic, and antiproliferative activities has been explored. To verify potential binding to anticancer drug targets, the interactions between the compounds and 14 selected targets have been analyzed by in silico modeling. Docking and binding affinity calculations were carried out, in comparison with known anticancer agents comprising ~1,500 published naturally occurring plant based compounds from around the world. The results reveal that African medicinal plants could represent a good starting point for the discovery of anticancer drugs. The small data set generated (named AfroCancer) has been made available for research groups working on virtual screening. PMID- 25116739 TI - A prochelator with a modular masking group featuring hydrogen peroxide activation with concurrent fluorescent reporting. AB - Metal chelators masked with protecting groups for targeted release have the potential to conditionally modulate cellular metals. We report a new route to prepare cis-cinnamate protecting groups that enabled development of a prochelator with chemical stimulus response, fluorescent reporting and active compound release in a single structure. PMID- 25116741 TI - In search of good ideas for occupational therapy. Previously published in Scandinavian Journal of Occupational Therapy 1994; 1: 7-15. AB - This paper explores the scholarly process by which good ideas may be sought for the future development of occupational therapy as an integrated profession. It is suggested that the assumptions of the science supporting practice need to be made explicit and that new ideas be generated which fit the dilemmas and puzzles of occupational therapy practice and are compatible with its view of human beings. PMID- 25116742 TI - Towards an ADL taxonomy for occupational therapists. Previously published in Scandinavian Journal of Occupational Therapy 1994; 1:69-76. AB - One of the main concepts in occupational therapy is human occupation. In occupational therapy there is a need for a common conceptual framework to assess and describe the ability of patients to perform occupational activities of daily living. The aim of this report was to develop a taxonomy concerning the activities of daily living (ADL). In the taxonomy, occupation has been defined and related to common concepts of disability. Ordinary ADL terms have been categorized into three levels: occupational forms, activities and actions. Different actions are components of and subordinated to superior activities. Experience shows that the ADL taxonomy contributes to a valid (content and construct) assessment of ADL, a common language for OTs and to a clearer picture of the patient's performance in daily life activities. PMID- 25116743 TI - Paradigms in occupational therapy. Previously published in Scandinavian Journal of Occupational Therapy 1994; 1: 53-58. AB - Every field of human occupation teems with patterns, which may be called "paradigms". This article is concerned with paradigms in the field of occupational therapy. The term "paradigm", which has become quite popular, perhaps too popular since the publication of Kuhn's famous book The Structure of Scientific Revolutions, has a complex semantic spectrum. Margaret Masterman has distinguished no less than twenty senses in Kuhn's writings. My use of the term, which has very little affinity with Kuhn's uses of it, will be defined in due course. PMID- 25116744 TI - A meditation on the use of hands. Previously published in Scandinavian Journal of Occupational Therapy 1995; 2: 153-166. AB - The theme of mind-body unity is fundamental to occupational therapy. Nonetheless, the field continues to embrace a dualism of mind and body. This dualism persists because the field views the body only as an object, ignoring how the body is lived. Drawing upon phenomenological discussions of bodily experience, this paper illustrates how the lived body is a locus of intelligence, intentionality, adaptiveness, and experience. It also considers the bodily ground of motivation and thought and discusses how the body constitutes and incorporates its world. Finally, the paper considers implications of the lived body for therapy. PMID- 25116745 TI - On the notion of health as ability. Previously published in Scandinavian Journal of Occupational Therapy 1996; 3: 101-105. AB - In this paper an outline of a theory of health based on the notion of ability is presented. A person's health is defined as his or her second-order ability to realize vital goals given standard or otherwise reasonable circumstances. The crucial concepts: vital goal, standard circumstance and second-order ability, are characterized in the paper. Special emphasis is laid upon the third concept, second-order ability, which is of particular importance for the theory of rehabilitation. PMID- 25116746 TI - Time use among individuals with persistent mental illness: identifying risk factors for imbalance in daily activities. Previously published in Scandinavian Journal of Occupational Therapy 2008; 15: 23-33. AB - The aim of this study was to investigate associations between time use in daily activities and sociodemographic and clinical factors in order to identify individuals with persistent mental illness at risk of having an imbalance in daily activities, as reflected in their time use and daily rhythm. Participants (n=103) were selected from a psychiatric outpatient unit using a randomized stratified selection procedure. The main findings indicated that time spent in daily activities increased with age, and that older individuals more often had a beneficial daily rhythm. Women and individuals living with children spent more time on self-care/self-maintenance than men and individuals living without children. Individuals with a diagnosis of psychosis spent less total time in daily activities than individuals with non-psychosis. In conclusion, general psychiatric symptoms, such as self-blame, anxiety, and difficulties in cooperating with others, explained most of the risk of spending little time in work/education as well as the risk of spending long periods asleep and having an adverse daily rhythm. A diagnosis of psychosis and high levels of general symptoms together explained most of the risk of having low total time use in activity. Factors such as age and living with children or not seemed to be important factors in relation to time use and daily rhythm. PMID- 25116747 TI - Occupational justice--bridging theory and practice. Previously published in Scandinavian Journal of Occupational Therapy 2010; 17: 57-63. AB - The evolving theory of occupational justice links the concept to social justice and to concerns for a justice of difference: a justice that recognizes occupational rights to inclusive participation in everyday occupations for all persons in society, regardless of age, ability, gender, social class, or other differences. The purpose of this descriptive paper is to inspire and empower health professionals to build a theoretical bridge to practice with an occupational justice lens. Using illustrations from a study of leisure and the use of everyday technology in the lives of very old people in Northern Sweden, the authors argue that an occupational justice lens may inspire and empower health professionals to engage in critical dialogue on occupational justice; use global thinking about occupation, health, justice, and the environment; and combine population and individualized approaches. The authors propose that taking these initiatives to bridge theory and practice will energize health professionals to enable inclusive participation in everyday occupations in diverse contexts. PMID- 25116748 TI - The Nordic Housing Enabler: Inter-rater reliability in cross-Nordic occupational therapy practice. Previously published in Scandinavian Journal of Occupational Therapy 2010; 17: 258-266. AB - This study addresses development of a content-valid cross-Nordic version of the Housing Enabler and investigation of its inter-rater reliability when used in occupational therapy rating situations, involving occupational therapists, clients, and their home environments. The instrument was translated from the original Swedish version of the Housing Enabler, and adapted according to accessibility norms and guidelines for housing design in Sweden, Denmark, Finland, and Iceland. This iterative process involved occupational therapists, architects, building engineers, and professional translators, resulting in the Nordic Housing Enabler. For reliability testing, the sampling strategy and data collection procedures used were the same in all countries. Twenty voluntary occupational therapists, pair-wise but independently of each other, collected data from 106 cases by means of the Nordic Housing Enabler. Inter-rater reliability was calculated by means of percentage agreement and kappa statistics. Overall good percentage agreement for the personal and environmental components of the instrument was shown, indicating that the instrument was sufficiently reliable for application in practice and research in the Nordic context. The varying kappa results highlight the need for further study in order to understand the influence of prevalence more profoundly, which should be kept in mind when interpreting the results. PMID- 25116749 TI - Qualitative approaches in occupational therapy research. Previously published in Scandinavian Journal of Occupational Therapy 2012; 19: 521-529. AB - OBJECTIVE: Development of research in occupational therapy requires a continuous critical discussion concerning methodological approaches. In this paper the authors wish to contribute to such a discussion by introducing the Formal Data Structure Analysis approach (FDSA) as a method for understanding people's experiences. METHODS AND RESULTS: A review of selected publications from occupational therapy journals between 2003 and 2005 illustrated that qualitative articles within occupational therapy publications were mainly descriptive in nature. This finding raises questions about how to develop new knowledge that contributes to occupational therapy. CONCLUSIONS: In this paper the authors suggest that it is possible to apply the FDSA approach not only when describing and categorizing qualitative phenomena, but also when aiming to reach an in-depth understanding of issues related to human meaning-making; for example, how we understand engagement in occupations or living with a disability. Examples of the application of the FDSA approach are included and discussed. PMID- 25116750 TI - Social participation: redesign of education, research, and practice in occupational therapy. Previously published in Scandinavian Journal of Occupational Therapy 2013; 20: 2-8. AB - There is growing attention to participation and social participation in literature and policy reports. Occupational therapists strongly believe that creating coherence between the person's occupations and environment will facilitate participation of each individual. Nowadays, societal developments such as "health literacy and self-management", "Web 2.0 social media", "empowering communities", and "Nothing About Us Without Us" increase opportunities for people to interact on different levels of social participation. Social participation can be used as an outcome, though it can also be seen as a means to change society and to develop solutions for barriers experienced by people with chronic diseases or disabilities. Societal developments will have an impact on social participation in terms of supporting each other and contributing to society. Additionally, these changes will have a major influence on the way we educate, conduct research, and deliver occupational therapy practice. PMID- 25116751 TI - Occupation-centred, occupation-based, occupation-focused: same, same or different? Previously published in Scandinavian Journal of Occupational Therapy 2013; 20: 162-173. AB - BACKGROUND: Since the beginning of the occupational therapy profession, engagement in occupation has been valued as the primary therapeutic agent as well as the goal of intervention. While there are few today who would not support this idea, occupational therapists continue to struggle with implementing their beliefs through "what we do" and "how we do it". Contributing to this problem is their failure to use terminology in a manner that clearly defines what and how occupational therapists do what they do in occupational therapy research, education, and practice. METHODS: The author will, therefore, first discuss some key occupational therapy terms and propose that they represent an occupation related taxonomy that can be used to more clearly define and describe for occupational therapists and others what they do and how they do what they do as occupational therapists. Then, with a goal of fostering critical self-reflection among occupational scientists and occupational therapy researchers, educators, and practitioners, the author will go through the stages of the occupational therapy process outlined in the Occupational Therapy Intervention Process Model (OTIPM) and demonstrate how a more precise use of this occupation-related taxonomy can facilitate maximizing the power of occupation in practice. PMID- 25116752 TI - Occupational therapists as contributors to health promotion. Previously published in Scandinavian Journal of Occupational Therapy 2014; 21: 82-89. AB - OBJECTIVE: This study was undertaken to explore the views of occupational therapists concerning their competences in health promotion, and their perceptions of how they apply these competences in their daily work. The study also elicited their views on the contributions that occupational therapists could make to health promotion if given the opportunity. METHODS: Data were collected in five focus-group discussions with 24 occupational therapists. These discussions were tape recorded and transcribed verbatim; data were analysed using qualitative content analysis. RESULTS: The main findings are that the informants took an individualized salutogenic approach in their work and rarely engaged in health promotion on a systemic or societal level. They believed that their patients and collaborating partners, as well as public officials, remained unaware of their competences in health promotion. CONCLUSIONS: The findings of this study could enrich the discussion among occupational therapists on how they could make a more significant contribution to health promotion on a broader level. PMID- 25116753 TI - An investigation of the support needs of men and partners throughout the prostate cancer journey. AB - OBJECTIVE: Prostate cancer is one of the mostly commonly diagnosed cancers in men. Unfortunately, the treatment for this cancer can have a number of negative side effects, both for the man himself and his partner. This study investigated the support needs of both men and partners throughout the prostate cancer journey and how this journey may be optimally managed. METHODS: Thirty-one men who had undergone prostate cancer treatment within the last 6 years and 31 partners answered a questionnaire, which explored support care issues as identified in the literature and from focus groups. RESULTS: Men and partners were moderately satisfied with information given regarding diagnosis, treatment and side effects, but partners were more satisfied with information relating to the particular chosen treatment. Men's understanding of their chosen treatment's potential side effects was significantly different from their understanding of diagnosis, cancer outcome, treatment options and selected treatment. Timing of information delivery was preferred by men at diagnosis, whereas partners preferred after the diagnosis. Men wanted more time to think about the diagnosis and treatment, whereas partners wanted an opportunity to discuss the diagnosis. The management of common side effects such as emotional changes, incontinence and erectile dysfunction was rated as 'somewhat' satisfactory. CONCLUSION: Men and partners may have different educational and supportive needs throughout the prostate cancer journey that require attention and tailored management. PMID- 25116754 TI - Downregulation of MHC-I expression is prevalent but reversible in Merkel cell carcinoma. AB - Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-associated skin cancer. Robust cellular immune responses are associated with excellent outcomes in patients with MCC, but these responses are typically absent. We determined the prevalence and reversibility of major histocompatibility complex class I (MHC-I) downregulation in MCC, a potentially reversible immune-evasion mechanism. Cell surface MHC-I expression was assessed on five MCC cell lines using flow cytometry as well as immunohistochemistry on tissue microarrays representing 114 patients. Three additional patients were included who had received intralesional IFN treatment and had evaluable specimens before and after treatment. mRNA expression analysis of antigen presentation pathway genes from 35 MCC tumors was used to examine the mechanisms of downregulation. Of note, 84% of MCCs (total n = 114) showed reduced MHC-I expression as compared with surrounding tissues, and 51% had poor or undetectable MHC-I expression. Expression of MHC-I was lower in polyomavirus-positive MCCs than in polyomavirus-negative MCCs (P < 0.01). The MHC I downregulation mechanism was multifactorial and did not depend solely on HLA gene expression. Treatment of MCC cell lines with ionizing radiation, etoposide, or IFN resulted in MHC-I upregulation, with IFNs strongly upregulating MHC-I expression in vitro, and in 3 of 3 patients treated with intralesional IFNs. MCC tumors may be amenable to immunotherapy, but downregulation of MHC-I is frequently present in these tumors, particularly those that are positive for polyomavirus. This downregulation is reversible with any of several clinically available treatments that may thus promote the effectiveness of immune stimulating therapies for MCC. PMID- 25116757 TI - Dorsal thalamic nuclei in Caiman crocodilus. AB - In Caiman crocodilus, identification of nuclei that comprise the dorsal thalamus was determined by: injections of retrograde tracers into cortex/pallium; injections of retrograde tracers into the noncortical telencephalon; and injections of anterograde tracers into thalamic nuclei. With the exception of nucleus dorsolateralis anterior, which has bilateral projections, all other dorsal thalamic nuclei send axons to terminate in the ipsilateral telencephalon. Nuclei that only projected to cortex/pallium were: dorsolateralis anterior; diagonalis; and dorsal geniculate. Neuronal aggregates that send axons that terminated in the dorsolateral area (dorsal ventricular ridge) included: rotundus; reuniens pars centralis and pars diffusa; medialis complex posterior; posterocentralis; and area ventrolateralis. Medialis complex anterior axons ended in the ventrolateral area (basal ganglia). Nucleus dorsomedialis projected to both cortex/pallium and the dorsolateral area. Based on the locus of telencephalic termination and fiber trajectory from the dorsal thalamus, nuclei of the dorsal thalamus were divided into several groups. PMID- 25116758 TI - Phasic alertness in a cued double-choice reaction time task: a Contingent Negative Variation (CNV) study. AB - A phasic change in alertness is produced every time that a warning stimulus precedes a target, and it enhances and maintains the response readiness to an impending stimulus. In the present study, we investigated the Contingent Negative Variation (CNV) phenomenon, as index of phasic alertness, during a S1-S2 paradigm in which the imperative stimulus was represented by a double-choice reaction time task, designed to increase the executive requests at S2. Subjects performed the task at three consecutive time points in order to explore the CNV activity over time. The repetition of a cued double-choice reaction time task reduced the reaction times (RTs), while CNV amplitude remained steady along the sessions. Our data suggest that the continuous recruitment of attentional resources does not undergo habituation when it is related to the brain activity required in the maintenance of working memory when the mental model of the stimulus environment is updated. PMID- 25116756 TI - Establishment of glycosaminoglycan assays for mucopolysaccharidoses. AB - Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the lysosomal enzymes essential for catabolism of glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction of multiple organs, resulting in distinct clinical manifestations. A range of methods have been developed to measure specific GAGs in various human samples to investigate diagnosis, prognosis, pathogenesis, GAG interaction with other molecules, and monitoring therapeutic efficacy. We established ELISA, liquid chromatography tandem mass spectrometry (LC-MS/MS), and an automated high throughput mass spectrometry (HT-MS/MS) system (RapidFire) to identify epitopes (ELISA) or disaccharides (MS/MS) derived from different GAGs (dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate). These methods have a high sensitivity and specificity in GAG analysis, applicable to the analysis of blood, urine, tissues, and cells. ELISA is feasible, sensitive, and reproducible with the standard equipment. HT-MS/MS yields higher throughput than conventional LC-MS/MS-based methods while the HT-MS/MS system does not have a chromatographic step and cannot distinguish GAGs with identical molecular weights, leading to a limitation of measurements for some specific GAGs. Here we review the advantages and disadvantages of these methods for measuring GAG levels in biological specimens. We also describe an unexpected secondary elevation of keratan sulfate in patients with MPS that is an indirect consequence of disruption of catabolism of other GAGs. PMID- 25116755 TI - A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF secreting breast tumor vaccine for HER2+ metastatic breast cancer. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines are bioactive, but limited by disease burden and immune tolerance. Cyclophosphamide augments vaccine activity in tolerant neu mice and in patients with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity in neu mice and patients with HER2+ metastatic breast cancer. Adding both cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2 specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We, therefore, conducted a single-arm feasibility study of cyclophosphamide, an allogeneic HER2+ GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in 20 patients with HER2+ metastatic breast cancer. Primary clinical trial objectives were safety and clinical benefit, in which clinical benefit represents complete response + partial response + stable disease. Secondary study objectives were to assess HER2-specific T-cell responses by delayed type hypersensitivity (DTH) and intracellular cytokine staining. Patients received three monthly vaccinations, with a boost 6 to 8 months from trial entry. This combination immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55% [95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%), respectively. Median progression-free survival and overall survival durations were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively. Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical benefit (95% CI, 18-90)], with a trend toward longer progression-free survival and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells progressively expanded across vaccination cycles. Further investigation of cyclophosphamide-modulated vaccination with trastuzumab is warranted. PMID- 25116759 TI - Disrupted MEK/ERK signaling in the medial orbital cortex and dorsal endopiriform nuclei of the prefrontal cortex in a chronic restraint stress mouse model of depression. AB - Depression is one of the most prevalent mental illnesses, and causes a constant feeling of sadness and lose of interest, which often leads to suicide. Evidence suggests that depression is associated with aberrant MEK/ERK signaling. However, studies on MEK/ERK signaling in depression have only been done in a few brain regions, such as the hippocampus and mesolimbic reward pathways. Recent studies also implicate the involvement of the prefrontal cortex in depression. Thus, we examined the changes in MEK/ERK signaling in subregions of the prefrontal cortex of C57BL/6 mice by immunohistochemistry using phospho-MEK1/2 (Ser 217/221) and ERK1/2 (Thr202/Tyr204) antibodies. Mice were subjected to 21 consecutive days of restraint stress (for 2h daily), and depression-like behavior was evaluated using a sociability test and tail suspension test. The antidepressant, imipramine (20mg/kg) was injected intraperitoneally 30min before restraint stress exposure. Chronic/repeated restraint stress produced depressive-like behavior, such as increased social avoidance in the social interaction test, and enhanced immobility time in the tail suspension test. This depressive behavior was ameliorated by imipramine. The behavioral changes well corresponded to a decrease in MEK/ERK immunoreactivity in the medial orbital (MO) cortex and dorsal endopiriform nuclei (DEn), which was averted by imipramine, but not in cingulate, prelimbic, infralimbic, and motor cortex. These results suggest that MEK/ERK signaling is disrupted in the DEn and MO subregions of the prefrontal cortex in the depressive phenotype, and that blocking a decrease in activated MEK/ERK is inherent to the antidepressant imipramine response. PMID- 25116761 TI - Magnetic circular dichroism of porphyrin lanthanide M3+ complexes. AB - Lanthanide complexes exhibit interesting spectroscopic properties yielding many applications as imaging probes, natural chirality amplifiers, and therapeutic agents. However, many properties are not fully understood yet. Therefore, we applied magnetic circular dichroism (MCD) spectroscopy, which provides enhanced information about the underlying electronic structure to a series of lanthanide compounds. The metals in the M(3+) state included Y, La, Eu, Tb, Dy, Ho, Er, Tm, Yb, and Lu; the spectra were collected for selected tetraphenylporphin (TPP) and octaethylporphin (OEP) complexes in chloroform. While the MCD and UV-VIS absorption spectra were dominated by the porphyrin signal, metal binding significantly modulated them. MCD spectroscopy was found to be better suited to discriminate between various species than absorption spectroscopy alone. The main features and trends in the lanthanide series observed in MCD and absorption spectra of the complexes could be interpreted at the Density Functional Theory (DFT) level, with effective core potentials on metal nuclei. The sum over state (SOS) method was used for simulation of the MCD intensities. The combination of the spectroscopy and quantum-chemical computations is important for understanding the interactions of the metals with the organic compounds. PMID- 25116760 TI - The requirement for protein kinase C delta (PRKCD) during preimplantation bovine embryo development. AB - Protein kinase C (PKC) delta (PRKCD) is a member of the novel PKC subfamily that regulates gene expression in bovine trophoblast cells. Additional functions for PRKCD in early embryonic development in cattle have not been fully explored. The objectives of this study were to describe the expression profile of PRKCD mRNA in bovine embryos and to examine its biological roles during bovine embryo development. Both PRKCD mRNA and protein are present throughout early embryo development and increases in mRNA abundance are evident at morula and blastocyst stages. Phosphorylation patterns are consistent with detection of enzymatically active PRKCD in bovine embryos. Exposure to a pharmacological inhibitor (rottlerin) during early embryonic development prevented development beyond the eight- to 16-cell stage. Treatment at or after the 16-cell stage reduced blastocyst development rates, total blastomere numbers and inner cell mass-to trophoblast cell ratio. Exposure to the inhibitor also decreased basal interferon tau (IFNT) transcript abundance and abolished fibroblast growth factor-2 induction of IFNT expression. Furthermore, trophoblast adhesion and proliferation was compromised in hatched blastocysts. These observations provide novel insights into PRKCD mRNA expression profiles in bovine embryos and provide evidence for PRKCD-dependent regulation of embryonic development, gene expression and post hatching events. PMID- 25116763 TI - Incidence of depression in patients with chronic hepatitis C receiving combination therapy of pegylated interferon-alpha and ribavirin. PMID- 25116762 TI - Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. AB - Post-operative pain affects millions of patients worldwide and the post-operative period has high rates of morbidity and mortality. Some of this morbidity may be related to analgesics. The aim of this review was to provide an update of current knowledge of adverse events (AE) associated with the most common perioperative non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The review is based on data from systematic reviews with meta-analyses of analgesic efficacy and/or adverse effects of perioperative non-opioid analgesics, and randomised trials and cohort/retrospective studies. Generally, data on AE are sparse and related to the immediate post-operative period. For paracetamol, the incidence of AEs appears trivial. Data are inconclusive regarding an association of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal impairment. Anastomotic leakage may be associated with NSAID usage. No firm evidence exists for an association of NSAIDs with impaired bone healing. Single dose GCCs were not significantly related to increased infection rates or delayed wound healing. Gabapentinoid treatment was associated with increased sedation, dizziness and visual disturbances, but the clinical relevance needs clarification. Importantly, data on AEs of combinations of the above analgesics are sparse and inconclusive. Despite the potential adverse events associated with the most commonly applied non-opioid analgesics, including their combinations, reporting of such events is sparse and confined to the immediate perioperative period. Knowledge of benefit and harm related to multimodal pain treatment is deficient and needs clarification in large trials with prolonged observation. PMID- 25116764 TI - The aesthetic eye. PMID- 25116765 TI - The methodological quality of systematic reviews comparing intravitreal bevacizumab and alternates for neovascular age related macular degeneration: A systematic review of reviews. AB - OBJECTIVE: To systematically collate and evaluate the evidence from recent SRs of bevacizumab for neo-vascular age related macular degeneration. MATERIALS AND METHODS: Literature searches were carried out in Medline, Embase, Cochrane databases for all systematic reviews (SRs) on the effectiveness of bevacizumab for neo-vascular age related macular degeneration, published between 2000 and 2013. Titles and abstracts were assessed against the inclusion/exclusion criteria using Joanna Briggs Institute (JBI) study eligibility form. Data was extracted using the JBI data extraction form. The quality of the SRs was assessed using JBI critical appraisal checklist for SRs. Decisions on study eligibility and quality were made by two reviewers; any disagreements were resolved by discussion. RESULTS: Nine relevant reviews were identified from 30 citations, of which 5 reviews fulfilled the review's inclusion criteria. All 5 reviews showed bevacizumab to be effective for neovascular AMD in the short-term when used alone or in combination with PDT or Pegaptanib. The average quality score of the reviews was 7; 95% confidence interval 6.2 to 7.8 (maximum possible quality score is 10). The selection and publication bias were not addressed in all included reviews. Three-fifth of the reviews had a quality score of 7 or lower, these reviews had some methodological limitations, search strategies were only identified in 2 (40%) reviews, independent study selection and quality assessment of included studies (4 (80%)) were infrequently performed. CONCLUSION: Overall, the reviews on the effectiveness of intravitreal/systemic bevacizumab for neovascular age-related macular generation (AMD) received good JBI quality scores (mean score = 7.0 points), with a few exceptions. The study also highlights the suboptimal reporting of SRs on this topic. Reviews with poor methodology may limit the validity of the reported results; hence efforts should be made to improve the design, reporting and publication of SRs across all journals. PMID- 25116766 TI - Nanostructure-based platforms-current prospective in ophthalmic drug delivery. AB - The topically applied drugs as drops are washed off from the eye in very short period, resulting in low ocular bioavailability of drugs. Number of approaches have been attempted to increase the bioavailability and the duration of action of ocular drugs. This review provides an insight into various novel approaches; hydrophilic nanogels, solid lipid nanoparticles, and nanosponges applied very recently in the delivery of insoluble drugs, prolonging the ocular residence time, minimize pre-corneal drug loss and, therefore, bioavailability and therapeutic efficacy of the drugs. Despite various scientific approaches, efficient ocular drug delivery remains a challenge for pharmaceutical scientists. PMID- 25116768 TI - The perceived personality traits of adults with digitally induced large angle strabismus and the impact of its correction. AB - PURPOSE: To ascertain the effect of digitally induced large angle strabismus and its correction on social bias against strabismic adults. SUBJECTS AND METHODS: This prospective, observational study included 10 orthotropic subjects whose face photographs were digitally altered to produce esotropia, exotropia, and hypertropia. Three batches of non-medical professionals, each consisting of 14 subjects, adjudged personality traits of the altered face photographs on a 10 item questionnaire. The same evaluators effected the appraisal of the orthotropic photographs. The personality score of the strabismic photograph of a subject was compared with its own orthotropic photograph. RESULTS: The 10 subjects whose photographs were digitally modified were of the same age (21 years) and had equal gender distribution. The evaluation of the photographs was performed by 42 evaluators aged 38.3 +/- 14.9 years, of whom 21 were males. Different personality traits were rated negatively in the strabismic photographs. The statistically significant negative impact was apparent on more number of personality traits for esotropia (7 out of 10) as compared to exotropia (4 out of 10) or hypertropia (3 out of 10). Rating of the strabismic photographs was significantly lower by female evaluators (P = 0.006). However, there was no difference whether the subject evaluating the photograph of the strabismic individual was of the same gender or the opposite gender. Internal consistency of the questionnaire was excellent (Cronbach's Alpha = 0.81). CONCLUSION: There was a significant negative impact of strabismus on the perceived personality traits of the digitally altered face photographs of the adults when compared to their orthotropic photograph. PMID- 25116769 TI - Spectral domain optical coherence tomography morphology in optic disc pit associated maculopathy. AB - PURPOSE: Our purpose was to study the clinical manifestation and course of optic pit maculopathy using Spectral Domain Optical Coherence Tomography (SD- OCT) images. MATERIALS AND METHODS: We used SD-OCT to examine 20 eyes of 19 patients with a macular detachment in combination with an optic. RESULTS: We observed five different fovea appearances in regard to fluid localization. In five eyes, we recorded changes in the fluid distribution with SD-OCT. In 17/20 eyes, we noted a communication between the perineural and subretinal and/or intraretinal space at the margin of the optic disc. CONCLUSION: 3-dimensional SD-OCT (3D-SDOCT) scans revealed a three-fold connection, between subretinal and intraretinal space, perineural space, and the vitreous cavity. Therefore, we suppose that intraretinal or subretinal fluid in optic pit maculopathy may have both a vitreous and cerebrospinal origin. A membrane, covering the optic nerve was noted in 14 cases. Even if it seems intact in some B-scans, it is not complete in others several micrometers apart. Additionally, we observed fluid accumulation below the margin of the optic disc and hyperreflective porous tissue in the optic disc excavation. Those findings do not influence the course of maculopathy. PMID- 25116770 TI - Comparison of ocular response analyzer parameters in primary open angle glaucoma and exfoliative glaucoma patients. AB - AIM: We sought to identify differences in the following measures of the ocular response analyser (ORA) between primary open angle glaucoma (POAG) and exfoliative glaucoma (EXG) patients: Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc) and Goldmann correlated intraocular pressure (IOPg). We also sought to relate these ORA measures with central corneal thickness (CCT). MATERIALS AND METHODS: This cross sectional study was conducted on a total of 162 individuals (46 EXG patients, 66 POAG patients and 50 healthy subjects without any ocular and systemic disease). ORA measurements were performed, and a minimum of three readings were obtained from each test subject. Groups were compared according to their ORA parameters. RESULTS: The mean CH levels of the EXG, POAG and healthy subjects were 7.6 +/- 2.1, 9.1 +/- 1.9 and 9.6 +/- 1.7 mmHg, respectively. CH was significantly lower in the EXG patients compared to the other groups (P < 0.001).The mean CRF levels of the EXG, POAG and healthy subjects were 9.0 +/- 2.0, 10.1 +/- 1.7 and 9.8 +/- 1.8mmHg, respectively. CRF levels in the eyes of the EXG patients were significantly lower compared to those of either the POAG patients (P = 0.005) or the healthy subjects (P = 0.03), but there was no significant difference in CRF levels between the POAG patients and the healthy subjects (P = 0.59). There was a significant positive correlation between CH and CCT in the EXG patients and healthy subjects (P < 0.001), but this correlation was not present in the POAG patients (P = 0.70). CONCLUSIONS: In this study, CH and CRF were found to be significantly reduced in the eyes of EXG patients compared to both the POAG patients and healthy subjects. Reduced CH in EXG patients might result in decreased support of peripapillary scleral structure and increased damage to the optic nerve during IOP increase. PMID- 25116771 TI - Personal A-constant in relation to axial length with various intraocular lenses. AB - PURPOSE: To study the relationship between the axial length and personal A constant for the 1-piece Tecnis (Abbott ZCB00), AcrySof MA60AC (Alcon) and the Quatrix aspheric preloaded (CROMA) intraocular lenses (IOL). MATERIALS AND METHODS: Patients matching the inclusion criteria were further subdivided according to the implanted IOL in this prospective comparative study. The obtained refractive outcomes were introduced into the formula installed in the biometry machine (Humphrey model 820 ultrasonic biometer) to obtain the personal A-constant for each eye. Polynomial regression analysis was done to study the individualized A-constant for each type of IOL in relation to preoperative axial length measurement. RESULTS: Two hundred and forty five eyes of 186 patients were enrolled into this study, of whom 73 eyes with Tecnis 1-piece, 116 eyes with MA60AC, and 56 eyes with Quatrix. The median of personalized A-constant for Tecnis 1-piece, MA60AC, and Quatrix were 119.21 (SD 1.3, Std. Mean error 0.15), 119 (SD 1.2, Std. Mean error 0.11) and 120.4 (SD 1.2, Std. Mean error 0.16) respectively. Regression plots for the same range of axial length among all the groups showed that the Tecnis1 group followed the same pattern of the Quatrix group in which there was a linear relationship of a trend towards myopia when the axial length had increased and a hyperopic shift when decreased. This relationship changed into a plateau when the axial length became in the range of 23.5 mm to 27 mm in the MA60AC group. CONCLUSIONS: Personal A-constant follows different trends with different IOLs even for the same range of axial length. PMID- 25116772 TI - Experiences with E-learning in Ophthalmology. AB - INTRODUCTION: E-learning is the use of internet for the purpose of education. E learning in medical education is at a nascent stage in our country. The present study was carried out with the purpose of introducing e-learning to third year medical students in the subject of Ophthalmology and taking feedback on their attitude towards the new methodology of teaching and evaluating. MATERIALS AND METHODS: E-learning was introduced to the seventh semester students of MBBS in the subject of Ophthalmology. The topics were converted to web friendly format and used for teaching and evaluating. Feedback was taken from the students on completion of the term on their attitudes towards e-learning and their views on the scope of e-learning in medical education. RESULTS: All the students agreed on the usefulness of e-learning in medical education. Eleven students (27.5%) found the medium of e-learning to be interesting, 15 (37.5%) considered it to be easy and accessible, 10 (25%) found it to be fast and easy, 4 (10%) considered it to be a medium which can give updated information. Twenty-three (57.5%) students considered that e-learning should be a medium of instruction in all the subjects, 15 (37.5%) students considered its usefulness in clinical subjects only. Twenty eight students (70%) desired that e-learning should be used to provide important notes, questions, MCQs on all topics. CONCLUSIONS: E-learning is well accepted as a medium of instruction by medical students. PMID- 25116773 TI - Outcomes of chronic macular hole surgical repair. AB - PURPOSE: To report visual and anatomic outcomes of chronic macular hole surgery, with analysis of pre-operative OCT-based hole size and post-operative closure type. SETTINGS AND DESIGN: An IRB-approved, retrospective case series of 26 eyes of 24 patients who underwent surgery for stage 3 or 4 idiopathic chronic macular holes at a tertiary care referral center. STATISTICAL ANALYSIS: Student's t-test. RESULTS: Nineteen of 26 eyes (73%) had visual improvement after surgery on most recent exam. Twenty-one of 26 eyes (81%) achieved anatomic closure; 16 of 26 eyes (62%) achieved type 1, and five of 26 eyes (19%) achieved type 2 closure. Post operative LogMAR VA for type 1 closure holes (0.49) was significantly greater than for type 2 closure and open holes (1.26, P < 0.003 and 1.10, P < 0.005, respectively), despite similar pre-operative VA (P = 0.51 and 0.68, respectively). Mean pre-operative hole diameter for eyes with type 1 closure, type 2 closure, and holes that remained open were 554, 929, and 1205 microns, respectively. Mean pre-operative hole diameter was significantly larger in eyes that remained open as compared to eyes with type 1 closure (P = 0.015). CONCLUSION: Vitrectomy to repair chronic macular holes can improve vision and achieve long-term closure. Holes of greater than 3.4 years duration were associated with a greater incidence of remaining open and type 2 closure. Larger holes (mean diameter of 1205 microns) were more likely to remain open after repair. PMID- 25116774 TI - Gain beyond cosmesis: demonstration of psychosocial and functional gains following successful strabismus surgery using the adult strabismus questionnaire adult strabismus 20. AB - BACKGROUND: Strabismus adversely affects psychosocial and functional aspects; while its correction impacts positively. AIM: The aim was to evaluate the gains in scores: Overall scores (OASs), psychosocial subscale scores (PSSs) and functional subscale scores (FSSs) following successful surgical alignment. SETTINGS AND DESIGN: We evaluated changed scores in the adult strabismus 20 (AS 20) questionnaire, administered before and after successful surgery. MATERIALS AND METHODS: Thirty adults horizontal strabismics, were administered the AS-20, at baseline, and at 6-week and 3-month. Group-wise analysis was carried out based on gender, strabismus type (esotropia [ET] or exotropia [XT]), back-ground and amblyopia. STATISTICAL ANALYSIS: We used Wilcoxon, and Mann-Whitney U-tests. Significance was set at P <= 0.05. RESULTS: At baseline, there were no significant differences within the groups, except that those with amblyopia significantly scored less than nonamblyopes in OAS (median scores: 53.8 vs. 71.3; P = 0.009) and FSS (56.3 vs. 85.3; P = 0.009). OAS, PSS and FSS showed significant gains at 6-week and 3-month (all Wilcoxon P < 0.001). Compared with males, females showed significantly more gain at 3-month (OAS: 37.9 vs. 28.7; P = 0.02), on account of PSS gain (49.6 vs. 37.5; P = 0.01). The ET performed better than XT only on the FSS at 6-week (28.7 vs. 15.0; P = 0.02). Vis-a-vis the nonamblyopes, the amblyopes showed significantly more benefit at 6-week alone (OAS: 18.7 vs. 28.7; P = 0.04), largely due to gains in PSS. CONCLUSIONS: Successful strabismus surgery has demonstrated significant gains in psychosocial, functional and overall functions. There is some evidence that gains may be more in females; with a trend to better outcomes in ET and amblyopes up to 6-week. PMID- 25116776 TI - Conjunctival intraepithelial neoplasia with corneal furrow degeneration. AB - A 68-year-old man presented with redness of left eye since six months. Examination revealed bilateral corneal furrow degeneration. Left eye lesion was suggestive of conjunctival squamous cell carcinoma, encroaching on to cornea. Anterior segment optical coherence tomography (AS-OCT) confirmed peripheral corneal thinning. Fluorescein angiography confirmed intrinsic vascularity of lesion. Patient was managed with "no touch" surgical excision, dry keratectomy without alcohol, cryotherapy, and primary closure. Pathologic examination of removed tissue confirmed clinical diagnosis. Management of this particular case required modification of standard treatment protocol. Unlike the alcohol-assisted technique of tumor dissection described, ethyl alcohol was not used for risk of corneal perforation due to underlying peripheral corneal thinning. Likewise, topical steroids were withheld in the post-operative period. Three weeks post operatively, left eye was healing well. Hence, per-operative usage of absolute alcohol and post-operative use of topical steroids may be best avoided in such eyes. PMID- 25116775 TI - Scleral depressed vitreous shaving, 360 laser, and perfluoropropane (C3 F8) for retinal detachment. AB - Purpose : To review the characteristics and outcomes of patients who underwent pars plana vitrectomy (PPV) with scleral depressed vitreous shaving, 360 degree peripheral endolaser, and 14% C3F8 gas for rhegmatogenous retinal detachment (RRD). Materials and Methods : A retrospective review of a consecutive series of patients who underwent primary repair of RRD by PPV with scleral depressed vitreous shaving, 360 degree peripheral endolaser, and 14% perfluoropropane (C 3 F 8 ) was conducted. Patients with less than 3 months follow-up, previous retinal surgery, and higher than grade B proliferative vitreoretinopathy were excluded. Results : Ninety-one eyes were included in the study. The mean age was 60.1 years. The mean follow-up was 13.7 months. The macula was detached in 63% (58/91) of the eyes. The reattachment rate after one surgical procedure was 95% (86/91) while overall reattachment rate was 100%. There was no statistically significant difference between reattachment rates of superior, nasal/temporal, or inferior RRDs. The mean final best corrected visual acuity (BCVA) was 20/40. Of all the patients, 66% of patients with macula-off RRDs had a final BCVA of 20/40 or better. CONCLUSIONS: PPV with scleral depressed vitreous shaving, 360 degree peripheral endolaser, and 14% C 3 F 8 leads to successful anatomical reattachment with visual improvement in patients with primary RRD. PMID- 25116777 TI - Luxation of eyeball following trauma: novel simple treatment. AB - Luxation of the eye globe is a rare occasion but it carries a risk of threat to permanent vision loss especially when associated with very high intraocular pressure. Appropriate intervention should be undertaken instantly. Predisposing factors include; eyes as in shallow orbital sockets, floppy eyelid syndrome, and exophthalmos. Prompt reduction results in restoration of full anatomical and visual recovery in otherwise healthy eyes. We report a case of globe luxation following trauma by door handle in a 65-year-old female, who recovered completely after reposition of the globe using Desmarres Lid Retractors. PMID- 25116778 TI - Feedback of final year ophthalmology postgraduates about their residency ophthalmology training in South India. AB - BACKGROUND AND AIMS: This study documents a survey of final-year ophthalmology postgraduate students on the subject of their residency training. A similar survey conducted 7 years ago published in IJO had concluded that the residency program was not up to expectations in many centers. Our study aimed to see if ophthalmology training and student perceptions differed since then. MATERIALS AND METHODS: For our study, we added a few questions to the same questionnaire used in the article "which is the best method to learn ophthalmology? Resident doctors' perspective of ophthalmology training" published in IJO, Vol. 56 (5). RESULTS: Forty-nine students (62.02%) returned completed forms. Most students desired an orientation program on entering residency, and wished to undergo diagnostic training initially. Case-presentation with demonstration and Wet-lab learning were most preferred. There was a big difference between the number of surgeries students actually performed and the number they felt would have been ideal. CONCLUSION: On the whole, the students still felt the need for improved training across all aspects of ophthalmology. PMID- 25116779 TI - Orbital cellulitis in a neonate of the tooth bud origin: a case report. AB - Orbital cellulitis is a serious, yet uncommon infection in neonates. It can result in significant sight and life threatening complications. Most commonly, it occurs secondarily as the result of a spread of infection from the sinuses. Orbital cellulitis, secondary to dental infection is rare. We hereby report a case of orbital cellulitis secondary to dental infection in a 15-day-old neonate without any systemic features. PMID- 25116780 TI - Combined special capsular tension ring and toric IOL implantation for management of post-DALK high regular astigmatism with subluxated traumatic cataract. AB - We report a case of 18-year-old male who has undergone phacoemulsification with implantation of toric IOL (AcrySof IQ SN6AT9) after fixation of lens capsule with Cionni's capsular tension ring (CTR) for subluxated traumatic cataract with high astigmatism after deep anterior lamellar keratoplasty (DALK). He underwent right eye DALK for advanced keratoconus four years earlier. He had history of trauma one year later with displaced clear crystalline lens into anterior chamber and graft dehiscence, which was repaired successfully. The graft survived, but patient developed cataract with subluxated lens, for which phacoemulsification with implantation of toric IOL was done. Serial topography showed regular corneal astigmatism of -5.50 diopter (K 1 42.75 D @130 degrees , K 2 48.25 D @40 degrees ). At 10-month follow-up, the patient has BCVA 20/30 with + 0.75 DS/- 1.75 DC @ 110 degrees . The capsular bag is quite stable with well-centered IOL. Combination of Cionni's ring with toric IOL could be a good option to manage such complex cases. PMID- 25116781 TI - Human ocular thelaziasis in Karnataka. AB - Thelaziasis is an arthropod-born disease of the eye and adnexa caused by Thelazia callipaeda, a nematode parasite transmitted by drosophilid flies to carnivores and humans. Because of its distribution mainly confined to South Asian countries and Russia, it is commonly known as Oriental eye worm. It is often under-reported and not been given its due clinical importance. We report first case of human thelaziasis from Hassan District, Karnataka. Five creamy-white, translucent worms were removed from the conjunctival sac of a 74-year-old male patient. Based on morphological characters, the worms were identified as nematodes belonging to the genus Thelazia and speciation was confirmed by CDC, Atlanta as callipaeda. Rarity of the disease and its ability to cause both extra and intraocular manifestations leading to ocular morbidity is the reason for presenting this case. From the available data, this is the first case report from Karnataka, India. PMID- 25116782 TI - Spontaneous resorption of sub-retinal cortical lens material. AB - We report a rare case of retained sub-retinal cortical material, which underwent spontaneous resorption. Patient presented with a left eye traumatic retinal detachment with a large retinal tear and posteriorly dislocated cataractous lens. Vitrectomy, lensectomy, silicone oil injection, and endolaser were performed. A good visual result was achieved. The report draws attention to this condition and highlights possible technique for minimizing risk of this complication in similar cases. PMID- 25116783 TI - A study regarding efficacy of various intraocular lens power calculation formulas in a subset of Indian myopic population. AB - Efficacy of intraocular lens power calculation formulas in a subset of Indian myopic population. Retrospectively reviewed 43 patients who underwent phacoemulsification with high axial length (AL) (>24.5 mm, range 24.75-32.35 mm). The power of the implanted intraocular lens (IOL) was used to calculate the predicted post-operative refractive error by four formulas: Sanders-Retzlaff Kraff (SRK II), SRK/T, Holladay 1, and Hoffer Q. The predictive accuracy of the formulas was analyzed by comparing the difference between the "actual" and "predicted" postoperative refractive errors. Repeated measures analysis of variance (ANOVA) tests were done to have pair-wise comparisons between the formulas and P < 0.05 was considered significant. A subcategory of axial length 24.5-26.5 mm was also tested. Holladay 1, Hoffer Q and SRK/T formulas showed a slight tendency toward resultant hyperopia, with mean error of +0.24 diopters (D), +0.58 D, and +0.92 D, respectively. The Holladay 1 formula provided the best predictive result overall. PMID- 25116784 TI - Anterior ischemic optic neuropathy in association with optic nervehead drusen. AB - Optic nerve head drusen (ONHD) are incidental ophthalmologic finding in the optic nerve. Patients with ONHD are often asymptomatic, but sometimes present with transient visual obscuration's (TVO), the reported incidence of which is 8.6%. Optic nerve head drusen are of two types: Superficial; visible and deep. The deep buried drusen mimic papilledema. Because of the varied presentation deep-buried drusen pose a diagnostic challenge to the ophthalmologists. In young patients, they are mistaken for papilledema as it is clinically difficult to detect a buried drusen in the optic nerve head, but are seen on the surface with aging as the retinal nerve fiber layer thins out. They are observed as pale yellow lesions more often located towards the poles. Clinical examination aided with diagnostic tests like computed tomography (CT) orbits and ultrasound B scan can help establish the diagnosis. Herein, we report a rare case of optic nerve head drusen in a young lady, who presented with loss of vision and clinical evaluation and investigations suggested ONHD with anterior ischemic optic neuropathy. PMID- 25116785 TI - Using the rebound tonometer to measure intraocular pressure in an anesthetized patient. PMID- 25116786 TI - Isolated complete bitemporal hemianopia in traumatic chiasmal syndrome. PMID- 25116787 TI - Massive submacular hemorrhage resulting in acute angle closure. PMID- 25116788 TI - Treatment options for myopic CNV--is photodynamic therapy still relevant? PMID- 25116789 TI - Varied phenotype of homocystinuria: possible diagnostic error. PMID- 25116790 TI - Patient satisfaction with conventional, complementary, and alternative treatment for cluster headache in a Norwegian cohort. AB - OBJECTIVE: Cluster headache (CH) may cause excruciating pain and not all patients get satisfactory help. Patient dissatisfaction with general practitioners (GPs) and neurologists, and use of complementary and alternative treatment (CAM) may reflect this. The authors studied patient satisfaction with doctors' treatment and use of CAM in a Norwegian CH cohort. SUBJECTS: A total of 196 subjects with a cluster headache diagnosis were identified in the registers of two neurological departments in North Norway. DESIGN: Of these, 70 with a confirmed diagnosis according to the second edition of the International Classification of Headache Disorders (ICHD-2) completed a comprehensive questionnaire with questions concerning satisfaction with doctors' treatment, use of CAM, and effect of both treatment regimes. RESULTS: Satisfaction with doctors' treatment was reported in 44/70 (63%) (GPs) and 50/70 (71%) (neurologists) while 39/70 (56%) were satisfied with both. Too long a time to diagnosis, median four years, was the most commonly reported claim regarding doctors' treatment. Use of CAM was reported in 27/70 (39%), and 14/70 (20%) reported experience with >= 2 CAM. Ten patients reported benefit from CAM (37% of "CAM users"). The average cluster period was longer in CAM-users than others (p = 0.02), but CAM use was not associated with age, education, use of medication, effect of conventional treatment, duration of cluster attacks, or time to diagnosis. CONCLUSION: About two-thirds of CH patients were satisfied with treatment from either GPs or neurologists, and about one-third had used CAM. Despite experiencing diagnostic delay and severe pain, cluster patients seem in general to be satisfied with doctors' conventional treatment. PMID- 25116791 TI - Xanthoceraside induces apoptosis in melanoma cells through the activation of caspases and the suppression of the IGF-1R/Raf/MEK/ERK signaling pathway. AB - Xanthoceraside, a saponin extracted from the husks of Xanthoceras sorbifolia Bunge, suppresses inflammation and oxidative stress. However, the antitumor properties of xanthoceraside as well as its mechanism of action remain unclear. Therefore, we proposed to investigate its potential anticancer property. In this study, the viability of cells was measured by the MTT assay. Cell cycle and mitochondrial membrane potential were measured by flow cytometry, and the expressions of procaspase-9, procaspase-3, Cyto.c, Apaf-1, Bcl-2, Bcl-xL, Bad, p53, and IGF-1R/Raf/MEK/ERK were tested by Western blotting. Xanthoceraside significantly inhibited the proliferation of human melanoma A375.S2 cells in a concentration- and time-dependent manner but did not impair the viability of normal cells (peripheral blood mononuclear cells). Further analysis revealed that xanthoceraside induced apoptosis by activating caspase-3 and caspase-9 in a time dependent manner through the mitochondrial pathway but did not activate caspase-8 in the cells. In addition, xanthoceraside inhibited the expression of the insulin like growth factor-1 receptor (IGF-1R), which is an important prosurvival, antiapoptotic signaling growth factor receptor that is frequently overexpressed in cancer cells and used as a therapeutic target for multiple cancers. Interestingly, xanthoceraside also decreased the expression of Raf, p-MEK, and p ERK, the downstream effectors of IGF-1R. Taken together, these findings indicate that xanthoceraside induces apoptosis through a mitochondria-mediated apoptotic pathway, which is induced by the downregulation of IGF-1R/Raf/MEK/ERK cascades in A375.S2 cells. PMID- 25116792 TI - Long-range chemical sensitivity in the sulfur K-edge X-ray absorption spectra of substituted thiophenes. AB - Thiophenes are the simplest aromatic sulfur-containing compounds and are stable and widespread in fossil fuels. Regulation of sulfur levels in fuels and emissions has become and continues to be ever more stringent as part of governments' efforts to address negative environmental impacts of sulfur dioxide. In turn, more effective removal methods are continually being sought. In a chemical sense, thiophenes are somewhat obdurate and hence their removal from fossil fuels poses problems for the industrial chemist. Sulfur K-edge X-ray absorption spectroscopy provides key information on thiophenic components in fuels. Here we present a systematic study of the spectroscopic sensitivity to chemical modifications of the thiophene system. We conclude that while the utility of sulfur K-edge X-ray absorption spectra in understanding the chemical composition of sulfur-containing fossil fuels has already been demonstrated, care must be exercised in interpreting these spectra because the assumption of an invariant spectrum for thiophenic forms may not always be valid. PMID- 25116793 TI - Dynamin-mediated lipid acquisition is essential for Chlamydia trachomatis development. AB - Chlamydia trachomatis is an obligate intracellular pathogen responsible for a high burden of human disease. Here, a loss-of-function screen using a set of lentivirally transduced shRNAs identified 14 human host cell factors that modulate C. trachomatis infectivity. Notably, knockdown of dynamin, a host GTPase, decreased C. trachomatis infectivity. Dynamin functions in multiple cytoplasmic locations, including vesicle formation at the plasma membrane and the trans-Golgi network. However, its role in C. trachomatis infection remains unclear. Here we report that dynamin is essential for homotypic fusion of C. trachomatis inclusions but not for C. trachomatis internalization into the host cell. Further, dynamin activity is necessary for lipid transport into C. trachomatis inclusions and for normal re-differentiation from reticulate to elementary bodies. Fragmentation of the Golgi apparatus is proposed to be an important strategy used by C. trachomatis for efficient lipid acquisition and replication within the host. Here we show that a subset of C. trachomatis infected cells displayed Golgi fragmentation, which was concurrent with increased mitotic accumulation. Golgi fragmentation was dispensable for dynamin-mediated lipid acquisition into C. trachomatis inclusions, irrespective of the cell cycle phase. Thus, our study reveals a critical role of dynamin in host-derived lipid acquisition for C. trachomatis development. PMID- 25116794 TI - A chemoenzymatic synthesis of hept-6-ene-2,5-diol stereomers: application to asymmetric synthesis of decarestrictine L, pyrenophorol, and stagonolide E. AB - The stereomers of hept-6-ene-2,5-diol derivatives were conceived as useful chiral intermediates and were synthesized starting from sulcatol using two lipase catalyzed acylation reactions as the key steps. The versatility of the intermediates was demonstrated by converting them to the titled tetrahydropyran, macrolide, and macrodiolide compounds using standard synthetic protocols. PMID- 25116796 TI - AEDs at your fingertips: automated external defibrillators on college campuses and a novel approach for increasing accessibility. AB - The use of automated external defibrillators (AEDs) increases survival in cardiac arrest events. Due to the success of previous efforts and free, readily available mobile mapping software, the discussion is to emphasize the importance of the use of AEDs to prevent sudden cardiac arrest-related deaths on college campuses and abroad, while suggesting a novel approach to aiding in access and awareness issues. A user-friendly mobile application (a low-cost iOS map) was developed at Florida State University to decrease AED retrieval distance and time. The development of mobile AED maps is feasible for a variety of universities and other entities, with the potential to save lives. Just having AEDs installed is not enough--they need to be easily locatable. Society increasingly relies on phones to provide information, and there are opportunities to use mobile technology to locate and share information about relevant emergency devices; these should be incorporated into the chain of survival. PMID- 25116797 TI - New methods for the synthesis of naphthyl amines; application to the synthesis of dihydrosanguinarine, sanguinarine, oxysanguinarine and (+/-)-maclekarpines B and C. AB - A new method for preparing naphthyl amines from 1,5 unsaturated dicarbonyl precursors is described; the utility of this new method was proven in the syntheses of several natural products, all containing the benzo[c]phenanthridine core and enabled by a radical promoted cyclisation of the naphthyl amine products formed in the key cyclisation. PMID- 25116798 TI - Drug-disease association and drug-repositioning predictions in complex diseases using causal inference-probabilistic matrix factorization. AB - The high incidence of complex diseases has become a worldwide threat to human health. Multiple targets and pathways are perturbed during the pathological process of complex diseases. Systematic investigation of complex relationship between drugs and diseases is necessary for new association discovery and drug repurposing. For this purpose, three causal networks were constructed herein for cardiovascular diseases, diabetes mellitus, and neoplasms, respectively. A causal inference-probabilistic matrix factorization (CI-PMF) approach was proposed to predict and classify drug-disease associations, and further used for drug repositioning predictions. First, multilevel systematic relations between drugs and diseases were integrated from heterogeneous databases to construct causal networks connecting drug-target-pathway-gene-disease. Then, the association scores between drugs and diseases were assessed by evaluating a drug's effects on multiple targets and pathways. Furthermore, PMF models were learned based on known interactions, and associations were then classified into three types by trained models. Finally, therapeutic associations were predicted based upon the ranking of association scores and predicted association types. In terms of drug disease association prediction, modified causal inference included in CI-PMF outperformed existing causal inference with a higher AUC (area under receiver operating characteristic curve) score and greater precision. Moreover, CI-PMF performed better than single modified causal inference in predicting therapeutic drug-disease associations. In the top 30% of predicted associations, 58.6% (136/232), 50.8% (31/61), and 39.8% (140/352) hit known therapeutic associations, while precisions obtained by the latter were only 10.2% (231/2264), 8.8% (36/411), and 9.7% (189/1948). Clinical verifications were further conducted for the top 100 newly predicted therapeutic associations. As a result, 21, 12, and 32 associations have been studied and many treatment effects of drugs on diseases were investigated for cardiovascular diseases, diabetes mellitus, and neoplasms, respectively. Related chains in causal networks were extracted for these 65 clinical-verified associations, and we further illustrated the therapeutic role of etodolac in breast cancer by inferred chains. Overall, CI-PMF is a useful approach for associating drugs with complex diseases and provides potential values for drug repositioning. PMID- 25116795 TI - Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients. AB - Bipolar disorder (BP) is a chronic psychiatric condition characterized by dynamic, pathological mood fluctuations from mania to depression. To date, a major challenge in studying human neuropsychiatric conditions such as BP has been limited access to viable central nervous system tissue to examine disease progression. Patient-derived induced pluripotent stem cells (iPSCs) now offer an opportunity to analyze the full compliment of neural tissues and the prospect of identifying novel disease mechanisms. We have examined changes in gene expression as iPSC derived from well-characterized patients differentiate into neurons; there was little difference in the transcriptome of iPSC, but BP neurons were significantly different than controls in their transcriptional profile. Expression of transcripts for membrane bound receptors and ion channels was significantly increased in BP-derived neurons compared with controls, and we found that lithium pretreatment of BP neurons significantly altered their calcium transient and wave amplitude. The expression of transcription factors involved in the specification of telencephalic neuronal identity was also altered. Control neurons expressed transcripts that confer dorsal telencephalic fate, whereas BP neurons expressed genes involved in the differentiation of ventral (medial ganglionic eminence) regions. Cells were responsive to dorsal/ventral patterning cues, as addition of the Hedgehog (ventral) pathway activator purmorphamine or a dorsalizing agent (lithium) stimulated expression of NKX2-1 (ventral identity) or EMX2 (dorsal) in both groups. Cell-based models should have a significant impact on our understanding of the genesis and therefore treatment of BP; the iPSC cell lines themselves provide an important resource for comparison with other neurodevelopmental disorders. PMID- 25116799 TI - Stimuli-responsive composite particles as solid-stabilizers for effective oil harvesting. AB - The polymer-grafted magnetic composite particles have been synthesized and developed to harvest oil by use of their speical wettability. Different from gravity-driven oil-water separation, the prepared polymer brushes-grafted magnetic composite particles can act as solid-stabilizers that diffuse to the oil water interfical region and effectively minimize the direct oil-water interfical area by volume exclusion, whereas the magnetic Fe3O4 core allows easy separation of Pickering emulsions from oil-water mixture under an external magnetic field. When the emulsions were heated from room temperature to 50 degrees C, the coil to-globule transition of poly(N-isopropylacrylamide) (PNIPAM) acts as the driving force for the destabilization of the emulsion, thereby achieving the release of oil. The novel materials can be used in aspects of oil-water separation, inducing oil droplet transport and release of lipophilic substrates. PMID- 25116800 TI - Stroke gait rehabilitation: is load perception a first step towards load control? PMID- 25116802 TI - Comparison of trends and outcomes of carotid artery stenting and endarterectomy in the United States, 2001 to 2010. AB - BACKGROUND: Given the controversy regarding whether carotid endarterectomy (CEA) or carotid artery stenting (CAS) may be superior for stroke prevention, it is uncertain how recent clinical evidence, guidelines, and reimbursement policies have influenced the volume and outcomes after these procedures. METHODS AND RESULTS: We conducted a serial, cross-sectional study with time trends of patients undergoing CAS (n=124 265) and CEA (n=1 260 647) between 2001 and 2010 from the Nationwide Inpatient Sample database. During the 10-year period, the frequency of CEA declined, whereas CAS use slowly increased. After multivariate propensity score-matched analysis, CAS was associated with an increased risk of death (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.40-2.04), stroke (OR, 1.43; 95% CI, 1.23-1.66), and major adverse events including death, stroke, and myocardial infarction (OR, 1.25; 95% CI, 1.13-1.39). In asymptomatic patients, there was no significant difference in major adverse events (OR, 1.08; 95% CI, 0.92-1.20; P=0.16 [P <0.001 for interaction between procedure type and symptom status]) between CAS and CEA. Importantly, there was a significant improvement in CAS outcomes during the course of 10 years (reduction in death [OR, 0.51; 95% CI, 0.49-0.67; P for trend=0.03] and major adverse events [OR, 0.75; 95% CI, 0.66-0.84; P for trend=0.05] comparing years 2010 versus 2001). CONCLUSIONS: In US hospitals between 2001 and 2010, CAS was associated with worse in-hospital outcomes, partly attributable to selection and ascertainment bias. Asymptomatic patients undergoing CAS versus CEA had similar adjusted rates of major adverse events. CAS outcomes improved significantly during the course of the decade likely attributable to improvements in patient selection, operator skills, and technological advancements. PMID- 25116801 TI - A mutation in the CASQ1 gene causes a vacuolar myopathy with accumulation of sarcoplasmic reticulum protein aggregates. AB - A missense mutation in the calsequestrin-1 gene (CASQ1) was found in a group of patients with a myopathy characterized by weakness, fatigue, and the presence of large vacuoles containing characteristic inclusions resulting from the aggregation of sarcoplasmic reticulum (SR) proteins. The mutation affects a conserved aspartic acid in position 244 (p.Asp244Gly) located in one of the high affinity Ca(2+) -binding sites of CASQ1 and alters the kinetics of Ca(2+) release in muscle fibers. Expression of the mutated CASQ1 protein in COS-7 cells showed a markedly reduced ability in forming elongated polymers, whereas both in cultured myotubes and in in vivo mouse fibers induced the formation of electron-dense SR vacuoles containing aggregates of the mutant CASQ1 protein that resemble those observed in muscle biopsies of patients. Altogether, these results support the view that a single missense mutation in the CASQ1 gene causes the formation of abnormal SR vacuoles containing aggregates of CASQ1, and other SR proteins, results in altered Ca(2+) release in skeletal muscle fibers, and, hence, is responsible for the clinical phenotype observed in these patients. PMID- 25116803 TI - alpha-Solanine inhibits invasion of human prostate cancer cell by suppressing epithelial-mesenchymal transition and MMPs expression. AB - alpha-Solanine, a naturally occurring steroidal glycoalkaloid found in nightshade (Solanum nigrum Linn.), was found to inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism involved in suppression of cancer cell metastasis by alpha-solanine remains unclear. This study investigates the suppression mechanism of alpha-solanine on motility of the human prostate cancer cell PC-3. Results show that alpha-solanine reduces the viability of PC-3 cells. When treated with non-toxic doses of alpha-solanine, cell invasion is markedly suppressed by alpha-solanine. alpha-Solanine also significantly elevates epithelial marker E-cadherin expression, while it concomitantly decreases mesenchymal marker vimentin expression, suggesting it suppresses epithelial mesenchymal transition (EMT). alpha-Solanine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN), but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), and tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Immunoblotting assays indicate alpha solanine is effective in suppressing the phosphorylation of phosphatidylinositide 3 kinase (PI3K), Akt and ERK. Moreover, alpha-solanine downregulates oncogenic microRNA-21 (miR-21) and upregulates tumor suppressor miR-138 expression. Taken together, the results suggest that inhibition of PC-3 cell invasion by alpha solanine may be, at least in part, through blocking EMT and MMPs expression. alpha-Solanine also reduces ERK and PI3K/Akt signaling pathways and regulates expression of miR-21 and miR-138. These findings suggest an attractive therapeutic potential of alpha-solanine for suppressing invasion of prostate cancer cell. PMID- 25116804 TI - Self-assembled micelles composed of doxorubicin conjugated Y-shaped PEG poly(glutamic acid)2 copolymers via hydrazone linkers. AB - In this work, micelles composed of doxorubicin-conjugated Y-shaped copolymers (YMs) linked via an acid-labile linker were constructed. Y-shaped copolymers of mPEG-b-poly(glutamate-hydrazone-doxorubicin)2 and linear copolymers of mPEG-b poly(glutamate-hydrazone-doxorubicin) were synthesized and characterized. Particle size, size distribution, morphology, drug loading content (DLC) and drug release of the micelles were determined. Alterations in size and DLC of the micelles could be achieved by varying the hydrophobic block lengths. Moreover, at fixed DLCs, YMs showed a smaller diameter than micelles composed of linear copolymers (LMs). Also, all prepared micelles showed sustained release behaviors under physiological conditions over 72 h. DOX loaded in YMs was released more completely, with 30% more drug released in acid. The anti-tumor efficacy of the micelles against HeLa cells was evaluated by MTT assays, and YMs exhibited stronger cytotoxic effects than LMs in a dose- and time-dependent manner. Cellular uptake studied by CLSM indicated that YMs and LMs were readily taken up by HeLa cells. According to the results of this study, doxorubicin-conjugated Y shaped PEG-(polypeptide)2 copolymers showed advantages over linear copolymers, like assembling into smaller nanoparticles, faster drug release in acid, which may correspond to higher cellular uptake and enhanced extracellular/intracellular drug release, indicating their potential in constructing nano-sized drug delivery systems. PMID- 25116805 TI - Ruthenium polypyridine complexes combined with oligonucleotides for bioanalysis: a review. AB - Ruthenium complexes are among the most interesting coordination complexes and they have attracted great attention over the past decades due to their appealing biological, catalytic, electronic and optical properties. Ruthenium complexes have found a unique niche in bioanalysis, as demonstrated by the substantial progress made in the field. In this review, the applications of ruthenium complexes coordinated with polypyridine ligands (and analogues) in bioanalysis are discussed. Three main detection methods based on electrochemistry, electrochemiluminescence, and photoluminscence are covered. The important targets, including DNA and other biologically important targets, are detected by specific biorecognition with the corresponding oligonucleotides as the biorecognition elements (i.e., DNA is probed by its complementary strand and other targets are detected by functional nucleic acids, respectively). Selected examples are provided and thoroughly discussed to highlight the substantial progress made so far. Finally, a brief summary with perspectives is included. PMID- 25116806 TI - Synthesis, immobilization and catalytic activity of a copper(II) complex with a chiral bis(oxazoline). AB - A chiral bis(oxazoline) bearing CH2OH groups was synthesized from a commercial bis(oxazoline) and characterized by 1H- and 13C-NMR, high resolution ESI-mass spectrometry and FTIR. The corresponding copper(II) complex was immobilized onto the surface of a mesoporous carbonaceous material (Starbon(r) 700) in which the double bonds had been activated via conventional bromination. The materials were characterized by elemental analysis, ICP-OES, XPS, thermogravimetry and nitrogen adsorption at 77 K. The new copper(II) bis(oxazoline) was tested both in the homogeneous phase and once immobilized onto a carbonaceous support for the kinetic resolution of hydrobenzoin. Both were active, enantioselective and selective in the mono-benzoylation of hydrobenzoin, but better enantioselectivities were obtained in the homogeneous phase. The heterogeneous catalyst could be separated from the reaction media at the end of the reaction and reused in another catalytic cycle, but with loss of product yield and enantioselectivity. PMID- 25116807 TI - Dissociative electron transfer to diphenyl-substituted bicyclic endoperoxides: the effect of molecular structure on the reactivity of distonic radical anions and determination of thermochemical parameters. AB - The heterogeneous electron transfer reduction of the bicyclic endoperoxide 1,4 diphenyl-2,3-dioxabicyclo[2.2.1]hept-5-ene (4) was investigated in N,N dimethylformamide at a glassy carbon electrode. The endoperoxide reacts by a concerted dissociative ET mechanism resulting in reduction of the O-O bond with an observed peak potential of -1.4 V at 0.2 V s-1. The major product (90% yield) resulting from the heterogeneous bulk electrolysis of 4 at -1.4 V with a rotating disk glassy carbon electrode is 1,4-diphenyl-cyclopent-2-ene-cis-1,3-diol with a consumption of 1.73 electrons per mole. In contrast, 1,4-diphenyl-2,3 dioxabicyclo[2.2.2]oct-5-ene (1), undergoes a two-electron reduction mechanism in quantitative yield. This difference in product yield between 1 and 4 is suggestive of a radical-anion mechanism, as observed with 1,4-diphenyl-2,3 dioxabicyclo-[2.2.2] octane (2) and 1,4-diphenyl-2,3-dioxabicyclo[2.2.1]heptane (3). Convolution potential sweep voltammetry is used to determine unknown thermochemical parameters of 4, including the O-O bond dissociation energy and the standard reduction potential and a comparison is made to the previously studied bicyclic endoperoxides 1-3 with respect to the effect of molecular structure on the reactivity of distonic radical anions. PMID- 25116809 TI - A novel mitovirus from Buergenerula spartinae infecting the invasive species Spartina alterniflora. PMID- 25116808 TI - Effect of chitosan on tobacco mosaic virus (TMV) accumulation, hydrolase activity, and morphological abnormalities of the viral particles in leaves of N. tabacum L. cv. Samsun. AB - The effect of chitosan on the development of infection caused by Tobacco mosaic virus (TMV) in leaves of Nicotiana tabacum L. cv. Samsun has been studied. It was shown that the infectivity and viral coat protein content in leaves inoculated with a mixture of TMV (2 MUg/mL) and chitosan (1 mg/mL) were lower in the early period of infection (3 days after inoculation), by 63% and 66% respectively, than in leaves inoculated with TMV only. Treatment of leaves with chitosan 24 h before inoculation with TMV also caused the antiviral effects, but these were less apparent than when the virus and polysaccharide were applied simultaneously. The inhibitory effects of the agent decreased as the infection progressed. Inoculation of leaves with TMV together with chitosan considerably enhanced the activity of hydrolases (proteases, RNases) in the leaves, in comparison with leaves inoculated with TMV alone. Electron microscope assays of phosphotungstic acid (PTA)-stained suspensions from infected tobacco leaves showed that, in addition to the normal TMV particles (18 nm in diameter, 300 nm long), these suspensions contained abnormal (swollen, "thin" and "short") virions. The highest number of abnormal virions was found in suspensions from leaves inoculated with a mixture of TMV and chitosan. Immuno-electron microscopy showed that "thin" virus particles, in contrast to the particles of normal diameter, lost the ability to bind to specific antiserum. It seems that the chitosan-induced activation of hydrolases stimulates the intracellular degradation of TMV particles and hence hydrolase activation may be considered to be one of the polysaccharide-mediated cellular defense mechanisms that limit virus accumulation in cells. PMID- 25116810 TI - Alterations of the synapse of the inner retinal layers after chronic intraocular pressure elevation in glaucoma animal model. AB - BACKGROUND: Dendrites of retinal ganglion cells (RGCs) synapse with axon terminals of bipolar cells in the inner plexiform layer (IPL). Changes in RGC dendrites and synapses between bipolar cells in the inner retinal layer may critically alter the function of RGCs in glaucoma. Recently, synaptic plasticity has been observed in the adult central nervous system, including the outer retinal layers. However, few studies have focused on changes in the synapses between RGCs and bipolar cells in glaucoma. In the present study, we used a rat model of ocular hypertension induced by episcleral vein cauterization to investigate changes in synaptic structure and protein expression in the inner retinal layer at various time points after moderate intraocular pressure (IOP) elevation. RESULTS: Synaptophysin, a presynaptic vesicle protein, increased throughout the IPL, outer plexiform layer, and outer nuclear layer after IOP elevation. Increased synaptophysin after IOP elevation was expressed in bipolar cells in the innermost IPL. The RGC marker, SMI-32, co-localized with synaptophysin in RGC dendrites and were significantly increased at 1 week and 4 weeks after IOP elevation. Both synaptophysin and postsynaptic vesicle protein, PSD-95, were increased after IOP elevation by western blot analysis. Ribbon synapses in the IPL were quantified and structurally evaluated in retinal sections by transmission electron microscopy. After IOP elevation the total number of ribbon synapses decreased. There were increases in synapse diameter and synaptic vesicle number and decreases in active zone length and the number of docked vesicles after IOP elevation. CONCLUSIONS: Although the total number of synapses decreased as RGCs were lost after IOP elevation, there are attempts to increase synaptic vesicle proteins and immature synapse formation between RGCs and bipolar cells in the inner retinal layers after glaucoma induction. PMID- 25116813 TI - Tools of the Trade: a tribute to Karen Denard Goldman, PhD, MCHES. PMID- 25116812 TI - Preparation of highly efficient MRI contrast agents through complexation of cationic Gd(III)-containing metallosurfactant with biocompatible polyelectrolytes. AB - Novel contrast agents were developed through assembling of Gd(III) -containing metallosurfactant (MS) with biocompatible polyelectrolytes sodium hyaluronate (HA), heparinsodium (HS) and dextran sulfate sodium (DSS). The formed polyelectrolyte-surfactant complexes showed different structural patterns as the charge ratio increased, including spherical aggregates, rod-like aggregates and network patterns in monovalent HA system, while spherical structures emerged in multivalent HS and DSS systems. Energy dispersive spectroscopy analysis and scanning electron microscopy mapping showed the presence of Gd(III) in these complexes. Inductively coupled plasma atomic emission spectrometry was further used to quantify the contents of Gd(III) in the assemblies. T1 magnetic resonance imaging showed that these Gd(III) -loaded complexes exhibited relaxivity of up to 63.81 mM(-1) s(-1) , much higher than that of Ominiscan (4.64 mM(-1) s(-1) ). The cytotoxicity test in vitro demonstrated the excellent biocompatibility of these complexes, which is essential for clinical application. PMID- 25116811 TI - Periodontal regeneration using strontium-loaded mesoporous bioactive glass scaffolds in osteoporotic rats. AB - Recent studies demonstrate that the rate of periodontal breakdown significantly increased in patients compromised from both periodontal disease and osteoporosis. One pharmacological agent used for their treatment is strontium renalate due to its simultaneous ability to increase bone formation and halt bone resorption. The aim of the present study was to achieve periodontal regeneration of strontium incorporated mesoporous bioactive glass (Sr-MBG) scaffolds in an osteoporotic animal model carried out by bilateral ovariectomy (OVX). 15 female Wistar rats were randomly assigned to three groups: control unfilled periodontal defects, 2) MBG alone and 3) Sr-MBG scaffolds. 10 weeks after OVX, bilateral fenestration defects were created at the buccal aspect of the first mandibular molar and assessed by micro-CT and histomorphometric analysis after 28 days. Periodontal fenestration defects treated with Sr-MBG scaffolds showed greater new bone formation (46.67%) when compared to MBG scaffolds (39.33%) and control unfilled samples (17.50%). The number of TRAP-positive osteoclasts was also significantly reduced in defects receiving Sr-MBG scaffolds. The results from the present study suggest that Sr-MBG scaffolds may provide greater periondontal regeneration. Clinical studies are required to fully characterize the possible beneficial effect of Sr-releasing scaffolds for patients suffering from a combination of both periodontal disease and osteoporosis. PMID- 25116814 TI - Tools of the Trade: a tribute to Karen Denard Goldman, PhD, MCHES. PMID- 25116815 TI - Neuropathic pain in two-generation twins carrying the sodium channel Nav1.7 functional variant R1150W. AB - We present clinical, neuropathological, and molecular genetic findings of a family with a new pain phenotype of the sodium channel gene SCN9A polymorphism R1150W. A 46-year-old woman presented with a 5-year history of episodic temperature- and exercise-dependent burning pain of the feet and lower legs associated with numbness of the distal upper and lower limbs. Her monozygotic twin sister and their mother and her twin presented similar symptoms. Clinical evaluation was normal except for a mild distal sensory deficit in fingers and feet. Electrophysiological testing was unremarkable, as were serum and cerebrospinal fluid laboratory findings. Skin biopsies of the distal lower limbs revealed an epidermal nerve fiber density at the lower limit of normal. Myelinated dermal nerve fibers showed elongated nodes of Ranvier, but normal distribution of nodal and paranodal proteins. Genetic testing for ion channel associated pain disorders revealed an amino acid R1150W substitution of the Nav1.7 sodium channel. The combination of a Nav1.7 polymorphism with dysmyelinating features in small-caliber peripheral nerves has not been described before and may suggest an explanation for the clinical syndrome in our patients. Treatment with the sodium channel blocker lamotrigine provided some relief, consistent with a role of sodium channel dysfunction in the pain syndrome of this family. PMID- 25116816 TI - A gamma-butyrolactone-sensing activator/repressor, JadR3, controls a regulatory mini-network for jadomycin biosynthesis. AB - Two regulatory genes, jadR2 and jadR3, in the jadomycin (jad) biosynthetic gene cluster of Streptomyces venezuelae encode homologues of gamma-butyrolactone receptor. JadR2 was previously shown to be a pseudo gamma-butyrolactone receptor. jadR3 is situated at the upstream of jadW123 encoding putative enzymes for gamma butyrolactone biosynthesis. Disruption of jadR3 resulted in markedly decreased production of jadomycin. Transcriptional analysis revealed that JadR3 represses jadW1, jadR2 and jadR3 but activates jadR1, the key activator gene for jadomycin biosynthesis. DNase I footprinting showed that JadR3 has four binding sites in the intergenic regions of jadR2-jadR1 and jadR3-jadW1. A JadR3 interactive molecule, SVB1, was purified from a large-scale fermentation and its structure found to be the same as SCB3, a gamma-butyrolactone from Streptomyces coelicolor, and was absent from a jadW123 mutant lacking jadomycin production. Addition of SVB1 or extract from S. coelicolor to the mutant restored jadomycin production. Overall, our results revealed that the association of JadR3 and SVB1 plays an important role in controlling a regulatory mini-network governing jadomycin biosynthesis, providing new insights into the ways in which gamma butyrolactone/receptor systems modulate antibiotic biosynthesis in Streptomyces. PMID- 25116818 TI - Implication of the Seoul declaration on public health of India. PMID- 25116817 TI - Somatization symptoms or interferon-related adverse events? Alexithymia and somatization in somatic symptom reporting of patients with chronic hepatitis C. PMID- 25116819 TI - Who's failure? encephalitis kills! AB - Encephalitis continues to be one of the most dreaded diagnoses because a high rate of morbidity and mortality are accepted even before starting the treatment. Most encephalitis cases occur in rural areas due to poor environmental sanitation, high-vector density, shortage of protected water supplies and lack of health education. Vaccination, environmental sanitation, vector control, health education and attention to prompt diagnosis and treatment in rural hospitals are the four essential pillars for reducing case fatality rate (CFR) of encephalitis. Frequently, virulence of the virus, immunological state of the host, unavailability of antiviral drugs and lack of enough tertiary care hospitals (TCH) are not responsible for the high CFR. Basic supportive care is not being practiced meticulously in Primary and Secondary Care Hospitals (PSCH), and their services are not being utilized fully. Main causes of high mortality and morbidity rates are hypoxia and ischemia of brain and other organs precipitated by preventable, controllable or treatable complications due to lack of basic medical and nursing care during transport to the TCH. Undiagnosed Rickettsial infections are suspected to be partly responsible for the high CFR in some areas. Improving rural hospitals and their ambulance services are the most economical way to reduce CFR. "Treatment facilities must be made available at places where cases occur." The best way to reduce CFR of encephalitis in developing and underdeveloped countries is to increase and improve PSCH and sensitize politicians, administrators, medical/nursing professionals and more importantly to impress and convince the public to utilize them. PMID- 25116820 TI - Public health challenges for universal health coverage. AB - The effective functioning of any health system requires an efficient public health service. Every human being has the right to enjoy "the highest attainable standard of health," which can be fulfilled by giving every man an affordable and equitable health system he deserves and demands. In these years, complex health changes have complicated the situation in India. Most important gaps in the health care include an understanding of the burden of the disease and what leads to and causes ill health, the availability and use of appropriate technology in the management of disease, ill health and health systems that have an impact on service delivery. Universal Health Coverage (UHC) has the potential to increase economic growth, improve educational opportunities, reduce impoverishment and inequalities, and foster social cohesion. Steps taken for achieving UHC will address the public health challenges and vice versa. PMID- 25116821 TI - Universal health coverage: the way forward. AB - Universal health coverage (UHC) is the means to provide accessible and appropriate health services to all citizens without financial hardships. India, an emerging economy with demographic window of opportunity has been facing dual burden of diseases in midst of multiple transitions. Health situation in the country despite quantum improvements in recent past has enormous challenges with urban-rural and interstate differentials. Successful national programs exists, but lack ability to provide and sustain UHC. Achieving UHC require sustained mechanisms for health financing and to provide financial protection through national health packages. There is a need to ensure universal access to medicines, vaccines and emerging technologies along with development of Human Resources for Health (HRH). Health service, management, and institutional reforms are required along with enhanced focus on social determinants of health and citizen engagement. UHC is the way for providing health assurance and enlarging scope of primary health care to nook and corners of the country. PMID- 25116822 TI - Assessment of quality of life during treatment of pediatric oncology patients. AB - BACKGROUND: The objective of this study was to assess health-related quality of life (HRQOL) of pediatric cancer patients and their parents in North India. MATERIALS AND METHODS: Seventy-five cancer children were assessed for HRQOL, using Lansky play performance scale and health utility index-2 (HUI-2). Fifty seven patients were followed-up after 4 months after therapy and reassessed. Their parents were also assessed using World Health Organisation (WHO) QOL BREF. Seventy five controls were also assessed and compared. RESULTS: Lansky and HUI-2 scores of patients, as well as WHO QOL BREF of parents were significantly poor in cancer patients when compared to controls. There was significant improvement after therapy in patients with lymphomas and miscellaneous tumors. Pain and self care were found to be maximally affected domains on HUI-2. CONCLUSIONS: Large prospective multicenter studies may be undertaken and hence that need based interventions can be planned. PMID- 25116823 TI - Health status and health care services in Uttar Pradesh and Bihar: a comparative study. AB - BACKGROUND: India's growth hype and dream of emerging as an economic superpower are being challenged today, among other things, by its failure to foster an inclusive growth path and provide to bulk of its population basic amenities of education and health. There exists great inequality at interstate and intrastate level in terms of the key components of human development-health and education. AIMS: The present work attempts to measure the extent of the inequality in health status and health care services in the two most populous states of India namely Uttar Pradesh and Bihar. MATERIALS AND METHODS: A detailed analysis of interdistrict and interregion disparity in health status and health care in the two states has been done using secondary data from Annual Health Survey (2011) and Statistical Diary (2011). Composite indices of health status and health services have been developed using Maher's normalization technique and principal component analysis. Inequality measures like co-efficient of variations have been used to measure the relevant disparities in the two states and explain the reason thereof. RESULTS: The work shows low overall health status and wide interdistrict and interregion health disparity in the two states with lower disparity in Uttar Pradesh as compared to Bihar in terms of health status and relatively high disparity in health infrastructure. One startling fact is existence of very low and insignificant correlation between infrastructure and outcome. CONCLUSION: The study finds health status is influenced not only by health care facilities, but a number of other factors principally government's commitment and policies. PMID- 25116824 TI - Prescribing behavior of diabetes treating physicians in selected health care facilities of the diabetic association of Bangladesh. AB - BACKGROUND: Practicing behavior of the physicians varies from population to population due to diverse socioeconomic, cultural, and professional factors. Evidence on these issues is almost nonexistent in the developing countries. OBJECTIVE: The prescribing behavior of diabetes treating physicians working in selected hospitals of the Diabetic Association of Bangladesh was studied along with the factors affecting those behaviors. MATERIALS AND METHODS: This was an observational study on 818 prescriptions given by 49 physicians working in 16 health care facilities, which were photocopied by a portable photocopier. The various components of the prescription were scrutinized for presence and absence, and evaluated independently by two expert Diabetologists for their qualitative aspects. RESULTS: The mean +/- standard deviation of the total prescribing score (expressed as percentage) was 60 +/- 11. Physicians scoring around or below 60% belonged more to lower age (<40 years), less experienced (<7 years) and mid position (Senior Medical Officers) groups. Most of them also had public medical college background. Physicians with Certificate Course on Diabetology (CCD) had significantly higher score compared with the Non-CCD group (P < 0.001). Direction and duration of drug use were absent in majority of prescriptions (72.0% and 61.6%), respectively. Symptoms were not written in 78.0% and the family histories were not recorded in 98.5% prescriptions. Diet (49.4%) and exercise (51.0%) related advices were not mentioned in a large number of prescriptions. Appropriate change of drug (78.2%) and proper use of drug (99.1%) and brand (93.8%) were found rational, but still, 22.4% of the prescriptions found illegible. CONCLUSION: A large proportion of prescriptions in Bangladesh related to diabetes care still lack standardization and acceptable quality. Nondrug related issues (such as history, symptoms, and dietary/exercise-related advices) are the most neglected ones in a prescription. PMID- 25116825 TI - Trends of chronic liver disease in a tertiary care referral hospital in Eastern India. AB - BACKGROUND: There is scarce Indian data on time trends of hepatitis, an impediment to formulate an effective public health policy on the matter. OBJECTIVE: The aim was to study secular trends and burden of hepatitis in a railway population. MATERIALS AND METHODS: Outdoor, indoor, endoscopy unit and mortality records of patients attending this hospital from January 2003 to December 2011 were searched manually and relevant parameters of hepatitis patients were noted, especially etiology, clinical features, treatment, and mortality. Cochran-Armitage trend test was used to test significance of any trend in these parameters. Binary logistic regression analysis of various factors was carried out to study their effect on the liver related mortality of hepatitis B and C cases and Kaplan-Meyer survival curves were generated for significant factors. Two-sided P < 0.05 was considered to be significant. RESULT: Chronic liver disease (CLD) due to alcohol showed a significant rising trend with early age (mean 48.4 years) and high percentage of decompensated disease (75%) at presentation and high early mortality (63%). No trend was observed for hepatitis B and C, but significant reduction in mortality was observed when definitive therapy was given. Cryptogenic CLD showed a decreasing trend though overall it still remained the most important etiology and survival was better compared with alcohol even with conservative therapy. Only 4% patients had hepatocellular carcinoma. CONCLUSION: A menace of alcohol related liver disease affecting young productive work force in this part of India is foreseen, which might impact the country's economy and mandates immediate containment policy. PMID- 25116827 TI - Obstetric near miss morbidity and maternal mortality in a Tertiary Care Centre in Western Rajasthan. AB - Obstetric near-miss (ONM) describes a situation of lethal complication during pregnancy, labor or puerperium in which the woman survives either because of medical care or just by chance. In a cross-sectional observational study, five factor scoring system was used to identify the near-miss cases from all the cases of severe obstetric morbidity. Assessment of the causes of maternal mortality and near-miss obstetric cases was done. The ONM rate in this study was 4.18/1000 live births. Totally 54 maternal deaths occurred during this period, resulting in a ratio of 202 maternal deaths per 100,000 live births. Hemorrhage, hypertension and sepsis were major causes of near-miss maternal morbidity and mortality, respectively in descending order. PMID- 25116826 TI - Prevalence of behavioral risk factors, overweight and hypertension in the urban slums of North 24 Parganas District, West Bengal, India, 2010. AB - Globally, 1 billion people live in slums. There are few reports of high prevalence of noncommunicable disease (NCD) risk factors among the urban poor. The prevalence of NCD risk factors in the slums in North 24 Parganas, West Bengal, India was estimated. Cross-sectional survey in 24 slums selected using cluster sampling method was conducted. Questionnaire for behavioral risk factors was used and anthropometric and blood pressure measurements were done. The study population included 1052 participants aged 25-64 years, 528 (50%) were males. Among males, 206 (39%) were current smokers and 154 (29%) were current alcohol users. Central obesity was prevalent among 32.8% males and 56.1% females and 115 (10.9%) had body mass index >=27.5 kg/m 2 . Hypertension was prevalent among 35% males and 33% females. We observed high prevalence of NCD risk factors among urban slum dwellers that need to be addressed with health promotion programs and strengthening of primary health care system. PMID- 25116828 TI - Prevalence and risk factors for Taenia solium taeniasis in Kaniyambadi block, Tamil Nadu, South India. PMID- 25116829 TI - The hookah experience: stop them before it's too late!!!! PMID- 25116830 TI - Public health dentistry education program in India. PMID- 25116831 TI - Modeling Zn2+ release from metallothionein. AB - Mammalian metallothioneins (MTs) comprise a Zn3Cys9 cluster in the beta domain and a Zn4Cys11 cluster in the alpha domain. They play a crucial role in storing and donating Zn(2+) ions to target metalloproteins and have been implicated in several diseases, thus understanding how MTs release Zn(2+) is of widespread interest. In this work, we present a strategy to compute the free energy for releasing Zn(2+) from MTs using a combination of classical molecular dynamics (MD) simulations, quantum-mechanics/molecular-mechanics (QM/MM) minimizations, and continuum dielectric calculations. The methodology is shown to reproduce the experimental observations that (1) the Zn-binding sites do not have equal Zn(2+) affinity and (2) the isolated beta domain is thermodynamically less stable and releases Zn(2+) faster with oxidizing agents than the isolated alpha domain. It was used to compute the free energies for Zn(2+) release from the metal cluster in the absence and presence of the protein matrix (protein architecture and coupled protein-water interactions) to yield the respective disulfide-bonded product. The results show the importance of the protein matrix as well as protein dynamics and coupled conformational changes in accounting for the differential Zn(2+)-releasing propensity of the two domains with oxidizing agents. PMID- 25116832 TI - Catalytic asymmetric reactions by metal and chiral phosphoric acid sequential catalysis. AB - Catalytic asymmetric reactions promoted by metal catalysts and chiral phosphoric acids have become useful processes for the preparation of structurally diverse and complex organic compounds. This JOCSynopsis provides an overview of the most recent developments made in studies of these reactions. The paper focuses mainly on sequential catalysis and relay catalysis, which are accomplished by employing a combination of metal complexes and chiral phosphoric acids. PMID- 25116833 TI - A new 1,2-ethanedione benzofurane derivative from Tephrosia purpurea. AB - A new 1,2-ethanedione benzofurane derivative, purpdione (1), was isolated from Tephrosia purpurea, together with seven known flavonoids, purpurenone (2), pongamol (3), ovalitenin A (4), karanjin (5), lanceolatin B (6), tachrosin (7) and villosinol (8). The new structure was elucidated based on the analysis of its spectroscopic data. The structures of the known compounds were identified by comparing their spectroscopic data with those reported in the literature. The isolates exhibited marginal ability to inhibit the settlement of barnacle (Balanus reticulatus). PMID- 25116834 TI - Testing the accuracy of an observation-based classifier for rapid detection of autism risk. AB - Current approaches for diagnosing autism have high diagnostic validity but are time consuming and can contribute to delays in arriving at an official diagnosis. In a pilot study, we used machine learning to derive a classifier that represented a 72% reduction in length from the gold-standard Autism Diagnostic Observation Schedule-Generic (ADOS-G), while retaining >97% statistical accuracy. The pilot study focused on a relatively small sample of children with and without autism. The present study sought to further test the accuracy of the classifier (termed the observation-based classifier (OBC)) on an independent sample of 2616 children scored using ADOS from five data repositories and including both spectrum (n=2333) and non-spectrum (n=283) individuals. We tested OBC outcomes against the outcomes provided by the original and current ADOS algorithms, the best estimate clinical diagnosis, and the comparison score severity metric associated with ADOS-2. The OBC was significantly correlated with the ADOS-G (r= 0.814) and ADOS-2 (r=-0.779) and exhibited >97% sensitivity and >77% specificity in comparison to both ADOS algorithm scores. The correspondence to the best estimate clinical diagnosis was also high (accuracy=96.8%), with sensitivity of 97.1% and specificity of 83.3%. The correlation between the OBC score and the comparison score was significant (r=-0.628), suggesting that the OBC provides both a classification as well as a measure of severity of the phenotype. These results further demonstrate the accuracy of the OBC and suggest that reductions in the process of detecting and monitoring autism are possible. PMID- 25116837 TI - Anion-pi interactions and positive electrostatic potentials of N-heterocycles arise from the positions of the nuclei, not changes in the pi-electron distribution. AB - We show that the positive electrostatic potentials and molecular quadrupole moments characteristic of pi-acidic azines, which underlie the ability of these rings to bind anions above their centres, arise from the position of nuclear charges, not changes in the pi-electron density distribution. PMID- 25116836 TI - Associations between past bullying experiences and psychosocial and academic functioning among college students. AB - OBJECTIVES: This study examined whether childhood bullying victimization was associated with psychosocial and academic functioning at college. PARTICIPANTS: The sample consisted of 413 first-year students from a large northeastern university. METHODS: Students completed an online survey in February 2012 that included items assessing past bullying involvement, current psychosocial and academic functioning, and victimization experiences since arriving at college. RESULTS: Regression analyses indicated that reports of past bullying and other peer victimization were associated with lower mental health functioning and perceptions of physical and mental health, but were not associated with perceptions of social life at college, overall college experience, or academic performance. CONCLUSIONS: Childhood bullying victimization is associated with poorer mental and physical health among first-year college students. Colleges should consider assessing histories of bullying victimization, along with other past victimization exposures, in their service provision to students. PMID- 25116835 TI - Plasma DYRK1A as a novel risk factor for Alzheimer's disease. AB - To determine whether apparent involvement of DYRK1A in Alzheimer's disease (AD) pathology makes it a candidate plasma biomarker for diagnosis, we developed a method to quantify plasma DYRK1A by immunoblot in transgenic mouse models having different gene dosages of Dyrk1a, and, consequently, different relative protein expression. Then, we measured plasma DYRK1A levels in 26 patients with biologically confirmed AD and 25 controls (negative amyloid imaging available on 13). DYRK1A was detected in transgenic mouse brain and plasma samples, and relative levels of DYRK1A correlated with the gene copy number. In plasma from AD patients, DYRK1A levels were significantly lower compared with controls (P<0.0001). Results were similar when we compared AD patients with the subgroup of controls confirmed by negative amyloid imaging. In a subgroup of patients with early AD (CDR=0.5), lower DYRK1A expression was confirmed. In contrast, no difference was found in levels of DYRK1B, the closest relative of DYRK1A, between AD patients and controls. Further, AD patients exhibited a positive correlation between plasma DYRK1A levels and cerebrospinal fluid tau and phosphorylated-tau proteins, but no correlation with amyloid-beta42 levels and Pittsburgh compound B cortical binding. DYRK1A levels detected in lymphoblastoid cell lines from AD patients were also lower when compared with cells from age-matched controls. These findings suggest that reduced DYRK1A expression might be a novel plasma risk factor for AD. PMID- 25116838 TI - Identification of agr-positive methicillin-resistant Staphylococcus aureus harbouring the class A mec complex by MALDI-TOF mass spectrometry. AB - A small peptide called PSM-mec is encoded on the type II, III and VIII SCCmec cassettes present in the genomes of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) strains. This peptide is excreted by agr-positive strains, which represent about 89% of the strains of our collection and can be identified by the presence of delta toxin in mass spectrometry. The presence of the peptide in the MALDI-TOF MS spectra of whole cells was proved by a knock-down experiment employing a clone that expressed antisense RNA to psm-mec. Furthermore, evaluation of a collection of clinical agr-positive MRSA and MSSA isolates and type strains showed that, using a detection window of m/z 2411-2419, the PSM-mec is detected by mass spectrometry of whole cells with a sensitivity of 0.95 and a specificity of 1, thereby enabling rapid identification of a subgroup of MRSA with a method that is used during routine identification procedures. PMID- 25116840 TI - Structural protein-ligand interaction fingerprints (SPLIF) for structure-based virtual screening: method and benchmark study. AB - Accurate and affordable assessment of ligand-protein affinity for structure-based virtual screening (SB-VS) is a standing challenge. Hence, empirical postdocking filters making use of various types of structure-activity information may prove useful. Here, we introduce one such filter based upon three-dimensional structural protein-ligand interaction fingerprints (SPLIF). SPLIF permits quantitative assessment of whether a docking pose interacts with the protein target similarly to a known ligand and rescues active compounds penalized by poor initial docking scores. An extensive benchmark study on 10 diverse data sets selected from the DUD-E database has been performed in order to evaluate the absolute and relative efficiency of this method. SPLIF demonstrated an overall better performance than relevant standard methods. PMID- 25116841 TI - Alison Jolly: a supremely social intelligence (1937-2014). PMID- 25116842 TI - The emergence of the Acheulean in East Africa--international workshop, Rome, "La Sapienza" University, September 12-13, 2013. PMID- 25116839 TI - Whole genome sequencing indicates Corynebacterium jeikeium comprises 4 separate genomospecies and identifies a dominant genomospecies among clinical isolates. AB - Corynebacterium jeikeium is an opportunistic pathogen which has been noted for significant genomic diversity. The population structure within this species remains poorly understood. Here, we explore the relationships among 15 clinical isolates of C. jeikeium (reference strains K411 and ATCC 43734, and 13 primary isolates collected over a period of 7 years) through genetic, genomic, and phenotypic studies. We report a high degree of divergence among strains based on 16S ribosomal RNA (rRNA) gene and rpoB gene sequence analysis, supporting the presence of genetically distinct subgroups. Whole genome sequencing indicates genomic-level dissimilarity among subgroups, which qualify as four separate and distinct Corynebacterium species based on an average nucleotide identity (ANIb) threshold of <95%. Functional distinctions in antibiotic susceptibilities and metabolic profiles characterize two of these genomospecies, allowing their differentiation from others through routine laboratory testing. The remaining genomospecies can be classified through a biphasic approach integrating phenotypic testing and rpoB gene sequencing. The genomospecies predominantly recovered from patient specimens does not include either of the existing C. jeikeium reference strains, implying that studies of this pathogen would benefit from examination of representatives from the primary disease-causing group. The clinically dominant genomospecies also has the smallest genome size and gene repertoire, suggesting the possibility of increased virulence relative to the other genomospecies. The ability to classify isolates to one of the four C. jeikeium genomospecies in a clinical context provides diagnostic information for tailoring antimicrobial therapy and may aid in identification of species-specific disease associations. PMID- 25116843 TI - On the cutting edge: new methods and theory for analyzing stone tools. PMID- 25116844 TI - Catastrophes in evolution: is Cuvier's world extinct or extant? PMID- 25116845 TI - In the eye (and ears) of the beholder: receiver psychology and human signal design. AB - Although the study of signals has been part of human behavioral ecology since the field's inception,(1) only recently has signaling theory become important to the evolutionary study of human behavior and culture.(2) Signaling theory's rise to prominence has been propelled mainly by applications of costly signaling theory,(3) which has shed light on a wide variety of human behaviors ranging from hunting(4) to religion.(5,6) Costly signaling rests on the idea that wasteful but highly visible traits and behaviors can be explained as honest indicators of underlying qualities that are otherwise difficult to detect. For example, a laborious hunting technique may serve as a display of skill on the part of the hunter, who may then be favorably perceived by potential mates and allies.(4) The costs of the activity ensure that the signal is honest, since unskilled hunters will not be able to perform as well. Despite the usefulness of this perspective, many such studies begin by documenting a costly behavior that is then explained with reference to costly signaling theory. Because such behaviors are easy to detect, they may be overemphasized in the literature.(7) Moreover, costly signaling theory by itself can explain neither all signals nor all aspects of signal design. In this review, we argue that a focus on the role that the psychology of the intended receiver plays in signal design can expand the scope of signaling theory as a promising avenue to explain human behavior. PMID- 25116846 TI - Applying socioendocrinology to evolutionary models: fatherhood and physiology. AB - Owing to humans' unique life history pattern, particularly comparatively short interbirth intervals, early weaning, and prolonged support of multiple dependents, human females have greater reproductive value and higher lifetime fertility, on average, than do their Great Ape counterparts. As hominin females began weaning their young early and "stacking" dependents of various ages, they must have had cooperative allomaternal care partners already in place or been successful at concurrently soliciting help to ensure a high rate of survival of their offspring. Following Hrdy, I define allomaternal care (and its derivatives, such as "allomothers" and "allomothering") as "care from anyone other than the mother," which thus encompasses a wide range of individuals, including fathers. Who the likely allomother candidates mothers were and what form that cooperation took remain intriguing, difficult-to-answer questions, which are limited, in some capacity, by the lines of evidence available to us. Here, I present a framework for the ways in which we can integrate neurobiological-endocrine and social behavioral data ("socioendocrinology") to contribute to this dialogue in terms of evaluating fathers' roles. PMID- 25116847 TI - Best practices for reporting on heterogeneous photocatalysis. PMID- 25116848 TI - Cocoa bioactive compounds: significance and potential for the maintenance of skin health. AB - Cocoa has a rich history in human use. Skin is prone to the development of several diseases, and the mechanisms in the pathogenesis of aged skin are still poorly understood. However, a growing body of evidence from clinical and bench research has begun to provide scientific validation for the use of cocoa-derived phytochemicals as an effective approach for skin protection. Although the specific molecular and cellular mechanisms of the beneficial actions of cocoa phytochemicals remain to be elucidated, this review will provide an overview of the current literature emphasizing potential cytoprotective pathways modulated by cocoa and its polyphenolic components. Moreover, we will summarize in vivo studies showing that bioactive compounds of cocoa may have a positive impact on skin health. PMID- 25116850 TI - Aggression and social experience: genetic analysis of visual circuit activity in the control of aggressiveness in Drosophila. AB - BACKGROUND: Animal aggressiveness is controlled by genetic and environmental factors. Among environmental factors, social experience plays an important role in modulating aggression in vertebrates and invertebrates. In Drosophila, pheromonal activation of olfactory neurons contributes to social suppression of aggression. While it was reported that impairment in vision decreases the level of aggression in Drosophila, it remains unknown if visual perception also contributes to the modulation of aggression by social experience. RESULTS: In this study, we investigate the role of visual perception in the control of aggression in Drosophila. We took several genetic approaches to examine the effects of blocking visual circuit activity on fly aggressive behaviors. In wild type, group housing greatly suppresses aggressiveness. Loss of vision by mutating the ninaB gene does not affect social suppression of fly aggression. Similar suppression of aggressiveness by group housing is observed in fly mutants carrying a mutation in the eya gene leading to complete loss of eye. Chronic visual loss does not affect the level of aggressiveness of single-housed flies that lack social experience prior to behavioral tests. When visual circuit activity is acutely blocked during behavioral test, however, single-housed flies display higher levels of aggressiveness than that of control flies. CONCLUSION: Visual perception does not play a major role in social suppression of aggression in Drosophila. For single-housed individuals lacking social experience prior to behavioral tests, visual perception decreases the level of aggressiveness. PMID- 25116852 TI - Air-stable solid aryl and heteroaryl organozinc pivalates: syntheses and applications in organic synthesis. AB - A wide range of air-stable, solid, polyfunctional aryl and heteroarylzinc pivalates were efficiently prepared by either magnesium insertion or Hal/Mg exchange followed by transmetalation with Zn(OPiv)2 (OPiv = pivalate). By reducing the amount of LiCl the air stability could be significantly enhanced compared with previously prepared reagents. An alternative route is directed magnesiation using TMPMgCl?LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by transmetalation with Zn(OPiv)2 or, for very sensitive substrates, direct zincation by using TMPZnOPiv. These zinc reagents not only show excellent stability towards air, but they also undergo a broad range of C-C bond-formation reactions, such as allylation and carbocupration reactions, as well as addition to aldehydes and 1,4-addition reactions. Acylation reactions can be performed by using an excess of TMSCl to overcome side reactions of the omnipresent pivalate anion. PMID- 25116853 TI - Creating electrochemical gradients by light: from bio-inspired concepts to photoelectric conversion. AB - Light is harvested by natural photosynthetic systems to generate electrochemical gradients that power various reactions. Implementing nature's lessons in photosynthesis holds great promise for technological advances. With a focus on designs and concepts, recent progress in generating electrochemical gradients by light, mimicking the two general types of photosynthetic centers in nature that make use of either light-induced charge separation or photo-isomerization are summarized here. Light induced electrochemical gradients pave new ways for photoelectric conversion. While extensive research in this direction has focused on light-induced charge separation, recent work has shown that energy conversion based on photo-isomerization is very promising. Photoswitchable compounds have been found in nature, such as the retinal molecule in bacteriorhodopsin. These compounds may form an attractive molecular basis for future progress in this field. PMID- 25116854 TI - Interferon-alpha-induced depression: A reply to the letters to the editor by Mahajan et al. and Porcelli et al. PMID- 25116851 TI - Emerin expression in well differentiated epithelial lesions of thyroid: implications in papillary thyroid carcinoma diagnosis and predicting malignant behavior. AB - Recently, it has been reported that identifying nuclear membrane irregularities with anti-emerin antibody is useful for papillary thyroid carcinoma diagnosis. However, literature regarding the significance of emerin immunohistochemistry in thyroid is limited. We evaluated the diagnostic accuracy of the well-established nuclear alterations, nuclear protrusions and recently described nuclear shapes (garlands and star-like shapes) with emerin immunohistochemistry and hematoxylin- eosin stain in thyroid lesions. We further evaluated the diagnostic accuracy measures of tissue microarrays evaluated with both stains, to detect whether emerin immunohistochemistry improves the diagnostic accuracy for papillary thyroid carcinoma. For papillary thyroid carcinoma, pseudo- inclusions were best performers with emerin (diagnostic accuracy: 0.91), whereas with hematoxylin- eosin diagnostic accuracy of grooves was the highest (0.92). For follicular variant of papillary thyroid carcinoma, with both stains, predominately oval nuclear shape had the best diagnostic performance (diagnostic accuracy: 0.95). Nuclear protrusions were poor identifiers for papillary thyroid carcinoma. However, with emerin immunohistochemistry, they could successfully identify malignancy in 83% of the cases. Using emerin immunohistochemistry, in addition to hematoxylin- eosin improved the diagnostic accuracy for papillary thyroid carcinoma when compared to hematoxylin- eosin evaluation only (sensitivity: 0.70 vs 0.86, negative predictive value: 0.81 vs. 0.94, diagnostic accuracy: 0.87 vs. 0.94). Consistent with the previous literature, our findings indicate that emerin immunohistochemistry may be used as an adjunct diagnostic method to identify papillary thyroid carcinoma. Additionally, we suggest that nuclear protrusions detected with emerin imunohistochemistry may be used as indicators of malignant behavior in small tissue samples of thyroid. PMID- 25116856 TI - Selenoproteins and selenium status in bone physiology and pathology. AB - BACKGROUND: Emerging evidence supports the view that selenoproteins are essential for maintaining bone health. SCOPE OF REVIEW: The current state of knowledge concerning selenoproteins and Se status in bone physiology and pathology is summarized. MAJOR CONCLUSIONS: Antioxidant selenoproteins including glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), as a whole, play a pivotal role in maintaining bone homeostasis and protecting against bone loss. GPx1, a major antioxidant enzyme in osteoclasts, is up-regulated by estrogen, an endogenous inhibitor of osteoclastogenesis. TrxR1 is an immediate early gene in response to 1alpha,25-dihydroxyvitamin D3, an osteoblastic differentiation agent. The combination of 1alpha,25-dihydroxyvitamin D3 and Se generates a synergistic elevation of TrxR activity in Se-deficient osteoblasts. Of particular concern, pleiotropic TrxR1 is implicated in promoting NFkappaB activation. Coincidentally, TrxR inhibitors such as curcumin and gold compounds exhibit potent osteoclastogenesis inhibitory activity. Studies in patients with the mutations of selenocysteine insertion sequence-binding protein 2, a key trans-acting factor for the co-translational insertion of selenocysteine into selenoproteins have clearly established a causal link of selenoproteins in bone development. Se transport to bone relies on selenoprotein P. Plasma selenoprotein P concentrations have been found to be positively correlated with bone mineral density in elderly women. GENERAL SIGNIFICANCE: A full understanding of the role and function of selenoproteins and Se status on bone physiology and pathology may lead to effectively prevent against or modify bone diseases by using Se. PMID- 25116857 TI - Expression, regulation and function of human metallothioneins in endothelial cells. AB - Metallothioneins (MTs) are small cysteine-rich proteins which are involved in e.g. metal homeostasis, metal detoxification and protection against oxidative stress. In addition, several MTs have been shown to regulate expression of proangiogenic growth factors like vascular endothelial growth factor. Detailed information about the expression and regulation of specific MT isoforms in endothelial cells (EC) is limited. We therefore performed extensive mRNA expression profiling of all known human MTs in EC. We found that the basal endothelial expression is restricted to MT1E, MT1X, MT2A, and MT3. Physiological activation of EC by exposure to serum increased the expression of MT1E and MT2A and induced the expression of MT1M. Furthermore, exposure to zinc or copper induced the expression of most MT1 isoforms, while hypoxia specifically increased the expression of MT1E, MT1M, MT1X, and MT3. Finally, knockdown of the dominant MT isoform in EC, i.e. MT2A, resulted in decreased proliferation and sprouting as well as in increased migration of human umbilical vein EC. Together, these findings provide a link between MTs and angiogenesis. PMID- 25116855 TI - Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum. AB - Lipoate scavenging from the human host is essential for malaria parasite survival. Scavenged lipoate is covalently attached to three parasite proteins: the H-protein and the E2 subunits of branched chain amino acid dehydrogenase (BCDH) and alpha-ketoglutarate dehydrogenase (KDH). We show mitochondrial localization for the E2 subunits of BCDH and KDH, similar to previously localized H-protein, demonstrating that all three lipoylated proteins reside in the parasite mitochondrion. The lipoate ligase 1, LipL1, has been shown to reside in the mitochondrion and it catalyses the lipoylation of the H-protein; however, we show that LipL1 alone cannot lipoylate BCDH or KDH. A second mitochondrial protein with homology to lipoate ligases, LipL2, does not show ligase activity and is not capable of lipoylating any of the mitochondrial substrates. Instead, BCDH and KDH are lipoylated through a novel mechanism requiring both LipL1 and LipL2. This mechanism is sensitive to redox conditions where BCDH and KDH are exclusively lipoylated under strong reducing conditions in contrast to the H protein which is preferentially lipoylated under less reducing conditions. Thus, malaria parasites contain two different routes of mitochondrial lipoylation, an arrangement that has not been described for any other organism. PMID- 25116859 TI - Nucleophilic bromodifluoromethylation of iminium ions. AB - A method for bromodifluoromethylation of iminium ions using Me3SiCF2Br is described. The reaction involves room temperature activation of the silicon reagent by HMPA to generate difluorocarbene, which upon interacting with excess of bromide ion provides bromodifluoromethyl carbanionic species. The iminium electrophiles are generated in situ from aldehydes, secondary amines, proton sponge, and silyl triflate. The reaction can be extended for introduction of chlorodifluoromethyl and iododifluoromethyl groups. PMID- 25116858 TI - Effects of galactosylation in immunoglobulin G from all-atom molecular dynamics simulations. AB - Explicit water atomistic molecular dynamics simulations (200 ns, ~330,000 atoms) were performed to study the effects of galactosylation in the Fc domain of immunoglobulin G1. Two glycoforms were simulated to observe changes in protein carbohydrate interactions and carbohydrate structure. A high degree of flexibility was observed in the small hinge region of the protein, while large domains remained stable. The hinge region flexibility allowed both translation and rotation of the domains relative to each other, resulting in a large number of possible conformations available. The distributions of rotational orientations between the Fab1 and Fab2 domains showed that while these domains are able to orient themselves rather freely pointing in space they rotated in unison to remain rotationally oriented at specific angles. Additionally, removing specific terminal galactose residues increased the mobility of the carbohydrate, resulting in different protein-carbohydrate interactions. Glycosylation has been suggested as a route to improve the aggregation resistance of monoclonal antibodies for therapeutic treatments to aid the immune system. The results presented here may provide insight into the search for IgG molecules with increased aggregation resistance to be used as monoclonal antibodies. PMID- 25116860 TI - Antioxidant activity and chemical composition of three Tunisian Cistus: Cistus monspeliensis, Cistus villosus and Cistus libanotis. AB - The chemical composition of three rockrose Cistus species, Cistus monspeliensis, Cistus libanotis and Cistus villosus, collected in Tunisia, was studied by HPTLC, focusing on the terpenes and phenols constituents. Diterpenes of Cistus are important as the main constituents of the leaf sticky aromatic resin, known as labdanum, which are highly appreciated in perfumery. Polyphenols in the methanolic extracts of each species were identified, quantified as total and as flavonoids and tannins, and tested for antioxidant activity. Diterpenes were evident in C. libanotis and C. monspeliensis, whereas they were practically absent in C. villosus; C. libanotis had higher phenolic amount, whereas antioxidant activities were important, but different according to the following tests: DPPH radical scavenging, conversion of the Fe(3+/)ferricyanide complex and inhibition of beta-carotene bleaching. The reported data confirm the validity of utilisation of Cistus sp. in marketed herbal products, as well as the relevant presence of diterpenes in species actually not used for labdanum production. PMID- 25116861 TI - Immunological effects of massage after exercise: A systematic review. AB - OBJECTIVE: The objective of this review was to determine whether immune parameters can be modulated by massage after intense physical activity. METHODS: A search was conducted in Pub Med Medline, PEDro, and Cochrane databases, using the key words: "massage", "myofascial release", "acupressure", "recovery", and "warm up" combined with "exercise", "exercise-induced muscle damage", "sport", "immunology", and lymphocytes" independently. Only controlled studies published between 1970 and 2012 were selected, with no restrictions regarding publication language. The CONSORT Declaration was applied to assess the quality of the selected studies. RESULTS: The initial search identified 739 publications in the databases, of which only 5 met the review inclusion criteria. A positive relationship between immunological recovery and post-exercise massage was reported by some of these studies but not by others. CONCLUSION: There is preliminary evidence that massage may modulate immune parameters when applied after exercise, but more research is needed to confirm this possibility. PMID- 25116863 TI - The influence of narrative practice techniques on child behaviors in forensic interviews. AB - During investigations of child sexual abuse, forensic interviewers must maintain a delicate balance of providing support for the child while collecting forensic evidence about the abuse allegation required for credible evidence for court purposes. The use of narrative practice techniques can achieve both goals by creating conditions that facilitate the possibility that children will feel safe enough to provide detailed descriptions of the alleged abuse. This article reports findings from an evaluation of a change in practice using the CornerHouse Forensic Interview Protocol in which narrative practice techniques were incorporated into the interview format. Findings show that children provided more detailed accounts of abuse when interviewers used open-ended questions and supportive statements through narrative practice. PMID- 25116864 TI - Caregiver-youth communication about sex in South Africa: the role of maternal child sexual abuse history. AB - Much of the research on child sexual abuse focuses on negative outcomes. This brief report explores a potentially protective parenting behavior among black South African female caregivers with and without a child sexual abuse history. Using cross-sectional baseline data, we hypothesized that caregiver child sexual abuse history would be positively associated with caregiver-youth sex communication and this relationship would be strongest for girls. Youth whose caregiver experienced child sexual abuse were more likely to report communicating with their caregiver about sex than youth whose caregivers did not experience child sexual abuse; however, this relation did not hold for caregiver reported communication. Child sexual abuse survivors' ability and decision to discuss sex with their youth has the potential to protect youth from sexual risk and demonstrates resilience among a group rarely acknowledged for positive parenting practices. PMID- 25116865 TI - How ineffective family environments can compound maldevelopment of critical thinking skills in childhood abuse survivors. AB - The high stress of childhood abuse is associated with neurobiological detriments to executive function. Child abuse survivors may also be cognitively and relationally disadvantaged as a result of being raised in emotionally impoverished families that lack cohesion, organization, flexibility, self expression, and moral and ethical values and fail to provide opportunities for effective learning. A review of literature demonstrates how dysfunctional family of origin environments common to child abuse survivors, concomitant with the extreme stress of overt acts of abuse, can act as a barrier to the development of higher-order critical thinking skills. The article concludes by discussing ramifications of critical thinking skill deficits in child abuse survivors and highlights the importance of integrating and prioritizing critical thinking skills training in treatment. PMID- 25116862 TI - Structural and functional connectivity of the human brain in autism spectrum disorders and attention-deficit/hyperactivity disorder: A rich club-organization study. AB - Attention-deficit/hyperactive disorder (ADHD) and autism spectrum disorders (ASD) are two of the most common and vexing neurodevelopmental disorders among children. Although the two disorders share many behavioral and neuropsychological characteristics, most MRI studies examine only one of the disorders at a time. Using graph theory combined with structural and functional connectivity, we examined the large-scale network organization among three groups of children: a group with ADHD (8-12 years, n = 20), a group with ASD (7-13 years, n = 16), and typically developing controls (TD) (8-12 years, n = 20). We apply the concept of the rich-club organization, whereby central, highly connected hub regions are also highly connected to themselves. We examine the brain into two different network domains: (1) inside a rich-club network phenomena and (2) outside a rich club network phenomena. The ASD and ADHD groups had markedly different patterns of rich club and non rich-club connections in both functional and structural data. The ASD group exhibited higher connectivity in structural and functional networks but only inside the rich-club networks. These findings were replicated using the autism brain imaging data exchange dataset with ASD (n = 85) and TD (n = 101). The ADHD group exhibited a lower generalized fractional anisotropy and functional connectivity inside the rich-club networks, but a higher number of axonal fibers and correlation coefficient values outside the rich club. Despite some shared biological features and frequent comorbity, these data suggest ADHD and ASD exhibit distinct large-scale connectivity patterns in middle childhood. PMID- 25116866 TI - Perpetration, revictimization, and self-injury: traumatic reenactments of child sexual abuse in a nonclinical sample of South African adolescents. AB - Risk factors for traumatic reenactments of child sexual abuse experiences (perpetration, revictimization, and self-injury) were examined in a sample of 718 South African secondary school adolescents. Logistic regression analyses indicated that the most consistent predictors of reenactments were a history of child sexual abuse (rape and/or indecent assault) and respondents' gender, with males being significantly more likely than females to report perpetration (OR = 13.5) and females being more likely to report revictimization (OR = 3.2) and self injury (OR = 2.5). An analysis restricted to respondents with a history of child sexual abuse indicated that negative abuse-related cognitions were the most consistent predictor of all forms of traumatic reenactment. PMID- 25116868 TI - Thermally activated polymorphic transition from a 1D ribbon to a 2D carpet: squaric acid on Au(111). AB - Polymorphic transition from the 1D ribbon to the 2D carpet superstructure of squaric acid molecules on Au(111) was achieved through a thermally activated process. Our combined STM and DFT study revealed that the molecular arrangements in 1D and 2D superstructures are determined by the stability of their conformational isomers and assembled structures, respectively. PMID- 25116867 TI - Small-size circulating endothelial microparticles in coronary artery disease. AB - OBJECTIVES: Several recent lines of evidence indicate that endothelial microparticles are a new biomarker that can be used to monitor endothelial dysfunction in coronary artery disease (CAD). However, data concerning the detection of small microparticles (diameter <0.5 um) are lacking. The aim of this study was to detect small-size endothelial microparticles (SEMPs) in CAD patients to monitor endothelial dysfunction. METHODS: In total, 19 CAD patients and 14 healthy subjects were recruited. The absolute numbers and percentages of CD31(+)/CD42b- SEMPs and CD62E(+) SEMPs were determined by flow cytometry. Clinical parameters were also recorded. RESULTS: The mean percentage of CD62E(+) SEMPs was higher in the CAD patient group than in the healthy subject group. The area under the receiver operating characteristic curve of the percentage of CD62E(+) SEMPs was 0.795, and the cut-off value was 1.35. There was no correlation between the percentage of CD62E(+) SEMPs and various clinical parameters. CONCLUSION: The percentage of CD62E(+) SEMPs is a potential biomarker for monitoring endothelial function in CAD. PMID- 25116869 TI - Widening and high inclination of the middle cerebral artery bifurcation are associated with presence of aneurysms. AB - BACKGROUND AND PURPOSE: The middle cerebral artery (MCA) bifurcation is a preferred site for aneurysm formation. Wider bifurcation angles have been correlated with increased risk of aneurysm formation. We hypothesized a link between the presence of MCA aneurysms and the angle morphology of the bifurcation. METHODS: Three-dimensional rotational angiography volumes of 146 MCA bifurcations (62 aneurysmal) were evaluated for angle morphology: parent-daughter angles (larger daughter F1, smaller daughter F2), bifurcation angle (F1+F2), and inclination angle (gamma) between the parent vessel axis and the plane determined by daughter vessel axes. Statistics were evaluated using Wilcoxon rank-sum analysis and area under the receiver operator characteristic curve. RESULTS: Aneurysmal bifurcations had wider inclination angle gamma (median 57.8 degrees versus 15.4 degrees ; P<0.0001). Seventy-five percent of aneurysmal MCAs had gamma >10 degrees , compared with 25% nonaneurysmal. F1 and F2, but especially F1+F2, were significantly larger in aneurysmal bifurcations (median 171.3 degrees versus 98.1 degrees ; P<0.0001). Sixty-seven percent of aneurysmal bifurcations had F1+F2 >161 degrees , compared with 0% nonaneurysmal MCAs. An optimal threshold of 140 degrees was established for F1+F2 (area under the curve, 0.98). Sixty-eight percent of aneurysms originated off the daughter branches. Seventy six percent of them originated off the branch with the largest branching angle, specifically if this was the smaller daughter branch. Wider F1+F2 correlated with aneurysm neck width, but not dome size. CONCLUSIONS: MCA bifurcations harboring aneurysms have significantly larger branching angles and more often originate off the branch with the largest angle. Wider inclination angle is strongly correlated with aneurysm presence, a novel finding. The results point to altered wall shear stress regulation as a possible factor in aneurysm development and progression. PMID- 25116870 TI - Effects of surgical revascularization on cerebral oxygen metabolism in patients with Moyamoya disease: an 15O-gas positron emission tomographic study. AB - BACKGROUND AND PURPOSE: This prospective study was aimed to evaluate the effects of surgical revascularization on cerebral oxygen metabolism in moyamoya disease. METHODS: This study included totally 69 hemispheres of 42 patients who underwent superficial temporal artery to middle cerebral artery anastomosis and indirect bypass for moyamoya disease between 2000 and 2011. There were 12 children and 30 adults. MRI and (15)O-gas positron emission tomography were performed before and 3 to 4 months after surgery. Hemodynamic and metabolic parameters were precisely quantified and statistically analyzed. RESULTS: Preoperative positron emission tomographic scans revealed that cerebral blood flow was decreased, cerebral blood volume was increased, and cerebral metabolic rate for oxygen was decreased in both pediatric and adult patients. Cerebral metabolic rate for oxygen reduction was observed in ~80% of pediatric (16/21; 76%) and adult hemispheres (38/48; 79%). Surgical revascularization resolved hemodynamic compromise in all operated hemispheres. Cerebral metabolic rate for oxygen significantly improved in pediatric patients without parenchymal lesions (n=8), but not those with parenchymal lesions (n=8). Multivariate analysis revealed that cerebral metabolic rate for oxygen significantly improved in younger adult patients without parenchymal lesions (P=0.0264; odds ratio, 0.88; 95% confidence interval, 0.79 0.99). CONCLUSIONS: Cerebral oxygen metabolism is significantly depressed in ~80% of the involved hemispheres of moyamoya disease and improves in pediatric and younger adult patients without parenchymal lesions after bypass surgery. Cerebral oxygen metabolism may be reversibly depressed in response to cerebral ischemia in them although the underlying mechanisms are still unclear. PMID- 25116871 TI - When you are old. PMID- 25116872 TI - Ethical approach to surrogate consent for hemicraniectomy in older patients with extensive middle cerebral artery stroke. PMID- 25116873 TI - Letter by Shang regarding article, "Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation". PMID- 25116875 TI - Report from the European Stroke Organization 2014. PMID- 25116874 TI - Plasma magnesium and risk of ischemic stroke among women. AB - BACKGROUND AND PURPOSE: Lower plasma magnesium levels may be associated with higher blood pressure and endothelial dysfunction, but sparse prospective data are available for stroke. METHODS: Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989 to 1990, incident ischemic strokes were identified and confirmed by medical records through 2006. We conducted a nested case-control analysis of 459 cases, matched 1:1 to controls on age, race/ethnicity, smoking status, date of blood draw, fasting status, menopausal status, and hormone use. We used conditional logistic regression models to estimate the multivariable adjusted association of plasma magnesium and the risk of ischemic stroke and ischemic stroke subtypes. RESULTS: Median magnesium levels did not differ between ischemic stroke cases and controls (median, 0.86 mmol/L for both; P=0.14). Conditional on matching factors, women in the lowest magnesium quintile had a relative risk of 1.34 (95% confidence interval, 0.86-2.10; P trend=0.13) for total ischemic stroke compared with women in the highest quintile. Additional adjustment for risk factors and confounders did not substantially alter the risk estimates for total ischemic stroke. Women with magnesium levels<0.82 mmol/L had significantly greater risk of total ischemic stroke (multivariable relative risk, 1.57; 95% confidence interval, 1.09 2.27; P=0.01) and thrombotic stroke (multivariable relative risk, 1.66; 95% confidence interval, 1.03-2.65; P=0.03) compared with women with magnesium levels>=0.82 mmol/L. No significant effect modification was observed by age, body mass index, hypertension, or diabetes mellitus. CONCLUSIONS: Lower plasma magnesium levels may contribute to higher risk of ischemic stroke among women. PMID- 25116876 TI - Coronary artery calcification, intima-media thickness, and ankle-brachial index are complementary stroke predictors. AB - BACKGROUND AND PURPOSE: Coronary artery calcification (CAC), a marker of coronary atherosclerosis, predicts stroke in addition to established risk factors. Whether CAC's predictive value can be improved by peripheral atherosclerosis markers, namely carotid intima-media thickness (CIMT) and ankle-brachial index (ABI), was unknown. METHODS: A total of 3289 participants of the population-based Heinz Nixdorf Recall study (45-75 years; 48.8% men) without previous stroke or coronary heart disease were evaluated for incident stroke for 9.0+/-1.9 years. CAC, CIMT, and ABI were examined as stroke predictors. RESULTS: Eighty-four strokes occurred during follow-up. In multivariable Cox proportional hazard regressions, CAC (hazard ratio, 1.45 [95% confidence interval, 1.11-1.88] per SD increase in ln(CAC+1); SD, 2.40), CIMT (1.34 [1.08-1.66] per SD increase; SD, 0.127 mm), and ABI (1.55 [1.32-1.82] per SD decrease; SD, 0.148) were associated with stroke in addition to established risk factors. When combined with each other, ln(CAC+1)'s hazard ratio remained similar when CIMT (1.41 [1.09-1.83]) was inserted into the multivariable model, but slightly decreased when ABI (1.31 [1.01-1.72]) or CIMT and ABI (1.29 [0.99-1.68]) were included. Although CAC alone did not significantly elevate the area under the curve in Harrell's c-statistics (by 0.009; P=0.379) in addition to established risk factors, the combination of CAC and ABI increased area under the curve (by 0.029; P=0.047), as did ABI (by 0.025; P=0.038) but not CIMT (by 0.002; P=0.795) alone. The combination of CAC and ABI also resulted in significant category-free net reclassification and integrated discrimination improvement. CONCLUSIONS: CAC, CIMT, and ABI provide complementary information about stroke risk. ABI, which is distinctive in a small subpopulation, had the highest and CIMT, which is distributed across a larger range of values, had the lowest predictive value. PMID- 25116877 TI - Features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. PMID- 25116879 TI - White matter perivascular spaces are related to cortical superficial siderosis in cerebral amyloid angiopathy. AB - BACKGROUND AND PURPOSE: We set out to investigate whether MRI-visible centrum semiovale perivascular spaces (CSO-PVS), a potential biomarker of impaired interstitial fluid drainage in sporadic cerebral amyloid angiopathy, is associated with cortical superficial siderosis (cSS), reflecting recurrent hemorrhage from severe leptomeningeal and superficial cortical vascular amyloid. METHODS: Retrospective multicenter cohort study of possible/probable cerebral amyloid angiopathy according to the Boston criteria. PVS were rated in basal ganglia and CSO (CSO-PVS) on axial T2-weighted sequences, using a validated 4 point visual rating scale and were classified as high (score>2) or low degree (score<=2) for prespecified analyses. Independent risk factors for high CSO-PVS degree were investigated in logistic regression. RESULTS: The final cohort consisted of 138 cerebral amyloid angiopathy patients (mean age, 71.8 years; 95% confidence interval, 70.2-73.4 years; 52.2% men). High CSO-PVS degree was present in 61.2% of cases. The prevalence of any cSS, and disseminated cSS (involving >3 sulci), was higher in patients with high versus low CSO-PVS degree (for any cSS 45.9% versus 13.5%; P<0.00005; for disseminated cSS 31.8% versus 0%; P<0.00005). In multivariable logistic regression analysis, cSS presence (odds ratio, 4.78; 95% confidence interval, 1.64-13.87; P=0.004) was an independent predictors of high CSO-PVS degree. We found no associations between basal ganglia PVS and cSS. CONCLUSIONS: High degree of CSO-PVS is highly prevalent in sporadic cerebral amyloid angiopathy and is related to cSS. Our findings suggest that severe leptomeningeal and cortical vascular amyloid (causing cSS) is related to impaired interstitial fluid drainage from cerebral white matter, although determining the causal direction of this relationship requires prospective studies. PMID- 25116880 TI - Evaluation of a patient with spinal cord infarction after a hypotensive episode. PMID- 25116881 TI - Use of Montreal Cognitive Assessment in patients with stroke. PMID- 25116878 TI - Associations between estimated glomerular filtration rate and stroke outcomes in diabetic versus nondiabetic patients. AB - BACKGROUND AND PURPOSE: Low estimated glomerular filtration rate (eGFR) is known to be associated with clinical adverse outcomes. However, whether diabetes mellitus influences the association between eGFR and prognosis of stroke is still not elucidated. METHODS: Prospective cohort of 17,280 (nondiabetic 12,498 and diabetic 4782) Chinese patients with acute stroke from the China National Stroke Registry and from abnormal glucose regulation in patients with acute stroke across China (ACROSS) between 2007 and 2009 were followed-up for 1 year for all cause mortality, stroke recurrence, and stroke disability related to baseline eGFR in the presence and absence of diabetes mellitus. RESULTS: Among nondiabetic patients, as compared with eGFR of 90 to 119 mL/min per 1.73 m2, the adjusted odds ratio of lower eGFR of <45 mL/min per 1.73 m2 was 2.79 (95% confidence interval, 2.09-3.73) for all-cause mortality, 2.28 (1.74-2.98) for stroke recurrence, and 1.53 (1.16-2.01) for stroke disability; higher eGFR of >=120 mL/min per 1.73 m2 was just significantly associated with higher risk of all cause mortality (odds ratio, 1.38; 95% confidence interval, 1.02-1.86) but not with other outcomes. In diabetic patients, the adjusted odds ratios of all-cause mortality, stroke recurrence, and stroke disability in lower eGFR were 2.16 (1.51 3.08), 1.43 (1.02-2.00), and 1.38 (0.98-1.95), respectively; higher eGFR was significantly associated with higher risks of all stroke outcomes. CONCLUSIONS: Decreased eGFR (<45 mL/min per 1.73 m2) is a strong predictor of all-cause mortality, stroke recurrence, and stroke disability in diabetic and nondiabetic patients with acute stroke. Increased eGFR (>=120 mL/min per 1.73 m2) is associated with all of stroke outcomes in diabetic patients and linked to all cause mortality in nondiabetic patients. PMID- 25116882 TI - Number of cerebral microbleeds and risk of intracerebral hemorrhage after intravenous thrombolysis. AB - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are found in a substantial proportion of patients with ischemic stroke eligible for treatment with intravenous thrombolysis. Until now, there is limited data on the impact of multiple CMBs on occurrence of intracerebral hemorrhage (ICH) after intravenous thrombolysis. METHODS: Between 2008 and 2013, all patients receiving MRI-based intravenous thrombolysis were identified within our prospective thrombolysis register. Number of CMBs was rated on pretreatment T2*-weighted MRI by a rater blinded to clinical data and follow-up. Outcomes of interest were occurrence of symptomatic ICH (sICH) and parenchymal hemorrhage (PH). RESULTS: Among 326 included patients, 52 patients had a single CMB (16.0%), 19 had 2 to 4 CMBs (5.8%), and 10 had >=5 CMBs (3.1%). Frequency of sICH/PH was 1.2%/5.7% in patients without CMBs, 3.8%/3.8% in patients with a single CMB, 10.5%/21.1% in patients with 2 to 4 CMBs, and 30.0%/30.0% in patients with >=5 CMBs, respectively (each P for trend<0.01). The unadjusted odds ratio per additional CMB for sICH was 1.19 (95% confidence interval, 1.07-1.33; P<0.01) and for PH was 1.13 (95% confidence interval, 1.03-1.24; P=0.01). Compared with patients without CMBs, both patients with 2 to 4 CMBs (P=0.02/P=0.02) and patients with >=5 CMBs (P<0.01/P<0.01) had significantly increased odds ratios for sICH and PH, whereas in patients with a single CMB, odds ratios were not significantly increased (P=0.21/P=0.59). The association of CMB burden with sICH/PH remained significant after adjustment for possible confounders (age, age-related white matter changes score, atrial fibrillation, onset-to-treatment time, prior statin use, and systolic blood pressure on admission). CONCLUSIONS: Our findings indicate a higher risk of sICH and PH after intravenous thrombolysis when multiple CMBs are present, with a graded relationship to increasing baseline CMB number. PMID- 25116883 TI - Response to letter regarding article, "Relative contributions of sympathetic, cholinergic, and myogenic mechanisms to cerebral autoregulation". PMID- 25116884 TI - Response to letter regarding article, "N-terminal pro-B-type natriuretic peptide and stroke risk: the Reasons for Geographic and Racial Differences in Stroke cohort". PMID- 25116887 TI - The benefits of a 'right-touch' approach to health care regulation. PMID- 25116885 TI - Encapsulated cells expressing a chemotherapeutic activating enzyme allow the targeting of subtoxic chemotherapy and are safe and efficacious: data from two clinical trials in pancreatic cancer. AB - Despite progress in the treatment of pancreatic cancer, there is still a need for improved therapies. In this manuscript, we report clinical experience with a new therapy for the treatment of pancreatic cancer involving the implantation of encapsulated cells over-expressing a cytochrome P450 enzyme followed by subsequent low-dose ifosfamide administrations as a means to target activated ifosfamide to the tumor. The safety and efficacy of the angiographic instillation of encapsulated allogeneic cells overexpressing cytochrome P450 in combination with low-dose systemic ifosfamide administration has now been evaluated in 27 patients in total. These patients were successfully treated in four centers by three different interventional radiologists, arguing strongly that the treatment can be successfully used in different centers. The safety of the intra-arterial delivery of the capsules and the lack of evidence that the patients developed an inflammatory or immune response to the encapsulated cells or encapsulation material was shown in all 27 patients. The ifosfamide dose of 1 g/m2/day used in the first trial was well tolerated by all patients. In contrast, the ifosfamide dose of 2 g/m2/day used in the second trial was poorly tolerated in most patients. Since the median survival in the first trial was 40 weeks and only 33 weeks in the second trial, this strongly suggests that there is no survival benefit to increasing the dose of ifosfamide, and indeed, a lower dose is beneficial for quality of life and the lack of side effects. This is supported by the one-year survival rate in the first trial being 38%, whilst that in the second trial was only 23%. However, taking the data from both trials together, a total of nine of the 27 patients were alive after one year, and two of these nine patients were alive for two years or more. PMID- 25116888 TI - Pharmacological consequences of inhaled drug delivery to small airways in the treatment of asthma. AB - Small peripheral airways are an important target for the anti-inflammatory treatment of asthma. To make anti-inflammatory drugs (inhaled corticosteroids [ICS]) effectively reach small airways, they should be delivered using inhalation techniques containing high proportions of fine or super-fine particles. Higher proportions of fine particles are associated with higher systemic absorption of ICS leading to an increased risk of endogenous cortisol suppression. Ciclesonide, despite the highest proportion of fine and super-fine particle fractions, is the only ICS not associated with an increased risk of systemic adverse effects, including cortisol suppression. In contrary to ICS, bronchodilators should not be administered to peripheral airways. This does not improve their efficacy and may increase their risk of cardiotoxicity. Thus, from a pharmacological point of view and the theory of aerosols' deposition, fixed combinations of ICS and long-acting beta agonists are always suboptimal. In many cases, the best solution may be to use fine-particle ciclesonide and a non-fine particle beta agonist administered from separate inhalers. PMID- 25116886 TI - Resuscitation speed affects brain injury in a large animal model of traumatic brain injury and shock. AB - BACKGROUND: Optimal fluid resuscitation strategy following combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remain controversial and the effect of resuscitation infusion speed on outcome is not well known. We have previously reported that bolus infusion of fresh frozen plasma (FFP) protects the brain compared with bolus infusion of 0.9% normal saline (NS). We now hypothesize reducing resuscitation infusion speed through a stepwise infusion speed increment protocol using either FFP or NS would provide neuroprotection compared with a high speed resuscitation protocol. METHODS: 23 Yorkshire swine underwent a protocol of computer controlled TBI and 40% hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for two hours prior to resuscitation with bolus FFP (n = 5, 50 ml/min) or stepwise infusion speed increment FFP (n = 6), bolus NS (n = 5, 165 ml/min) or stepwise infusion speed increment NS (n = 7). Hemodynamic variables over a 6-hour observation phase were recorded. Following euthanasia, brains were harvested and lesion size as well as brain swelling was measured. RESULTS: Bolus FFP resuscitation resulted in greater brain swelling (22.36 +/- 1.03% vs. 15.58 +/- 2.52%, p = 0.04), but similar lesion size compared with stepwise resuscitation. This was associated with a lower cardiac output (CO: 4.81 +/- 1.50 l/min vs. 5.45 +/- 1.14 l/min, p = 0.03). In the NS groups, bolus infusion resulted in both increased brain swelling (37.24 +/- 1.63% vs. 26.74 +/- 1.33%, p = 0.05) as well as lesion size (3285.44 +/- 130.81 mm(3) vs. 2509.41 +/- 297.44 mm3, p = 0.04). This was also associated with decreased cardiac output (NS: 4.37 +/- 0.12 l/min vs. 6.35 +/- 0.10 l/min, p < 0.01). CONCLUSIONS: In this clinically relevant model of combined TBI and HS, stepwise resuscitation protected the brain compared with bolus resuscitation. PMID- 25116889 TI - Mechanistic studies of Gd3+-based MRI contrast agents for Zn2+ detection: towards rational design. AB - A series of novel pyridine-based Gd(3+) complexes have been prepared and studied as potential MRI contrast agents for Zn(2+) detection. By independent assessment of molecular parameters affecting relaxivity, we could interpret the relaxivity changes observed upon Zn(2+) binding in terms of variations of the rotational motion. PMID- 25116891 TI - Reliability in psychiatric diagnosis with the DSM: old wine in new barrels. PMID- 25116890 TI - A bioenergetic basis for membrane divergence in archaea and bacteria. AB - Membrane bioenergetics are universal, yet the phospholipid membranes of archaea and bacteria-the deepest branches in the tree of life-are fundamentally different. This deep divergence in membrane chemistry is reflected in other stark differences between the two domains, including ion pumping and DNA replication. We resolve this paradox by considering the energy requirements of the last universal common ancestor (LUCA). We develop a mathematical model based on the premise that LUCA depended on natural proton gradients. Our analysis shows that such gradients can power carbon and energy metabolism, but only in leaky cells with a proton permeability equivalent to fatty acid vesicles. Membranes with lower permeability (equivalent to modern phospholipids) collapse free-energy availability, precluding exploitation of natural gradients. Pumping protons across leaky membranes offers no advantage, even when permeability is decreased 1,000-fold. We hypothesize that a sodium-proton antiporter (SPAP) provided the first step towards modern membranes. SPAP increases the free energy available from natural proton gradients by ~60%, enabling survival in 50-fold lower gradients, thereby facilitating ecological spread and divergence. Critically, SPAP also provides a steadily amplifying advantage to proton pumping as membrane permeability falls, for the first time favoring the evolution of ion-tight phospholipid membranes. The phospholipids of archaea and bacteria incorporate different stereoisomers of glycerol phosphate. We conclude that the enzymes involved took these alternatives by chance in independent populations that had already evolved distinct ion pumps. Our model offers a quantitatively robust explanation for why membrane bioenergetics are universal, yet ion pumps and phospholipid membranes arose later and independently in separate populations. Our findings elucidate the paradox that archaea and bacteria share DNA transcription, ribosomal translation, and ATP synthase, yet differ in equally fundamental traits that depend on the membrane, including DNA replication. PMID- 25116892 TI - Peromyscus leucopus mice: a potential animal model for haematological studies. AB - Peromyscus leucopus mice share physical similarities with laboratory mice Mus musculus (MM) but have higher agility and longer lifespan. We compared domesticated P. leucopus linville (PLL) and M. musculus C57BL/6 (MMB6) mice for cellular composition of peripheral blood (PB), bone marrow (BM) and spleen. PLL mice had significantly fewer platelets and significantly more monocytes in the blood, and notably fewer megakaryocytes in the BM. Spleens of PLL mice were significantly smaller, with 50% fewer cells and reduced 'red pulp'. There was no obvious haematological change in PLL mice between 2-8 and 16-26 months of age, except for a significant increase in blood monocytes. Cellular reactive oxygen species (ROS) content showed no change with age but differed significantly between different cell types. Treating two to eight month-old PLL mice with antioxidant N-acetylcysteine in drinking water for three months did not affect cellular ROS content, but increased blood leucocytes especially the concentration of monocytes. The low platelets, low megakaryocytes, high monocytes and low splenic erythropoiesis in PLL mice resemble human measurements better than the values seen in MMB6. PMID- 25116893 TI - Inhibition of microRNA-125a promotes human endothelial cell proliferation and viability through an antiapoptotic mechanism. AB - The microRNA-125a (miR-125a) is highly expressed in endothelial cells, but its role in vascular biology is not known. Endothelial cell proliferation and viability play an important role in endothelial healing, and we hypothesize that miR-125a regulates this process. The aim of the present study was to investigate if miR-125a controls human endothelial cell proliferation, viability and endothelial healing, and to assess the mechanisms involved. We showed that overexpression of miR-125a by transfection with miR-125a mimic reduced human umbilical vein endothelial cell (HUVEC) proliferation and viability, and stimulated apoptosis as demonstrated by a miR-125a-induced increase of the proportion of annexin V-positive cells monitored by flow cytometry. Moreover, we showed that the miR-125a mimic downregulated the antiapoptotic Bcl2 protein and upregulated caspase 3, suggesting that these two proteins represent molecular targets for miR-125a. Accordingly, transfection with miR-125a inhibitor, downregulating miR-125a expression, promoted HUVEC proliferation and viability, and reduced apoptosis. Importantly, transfection with miR-125a inhibitor promoted HUVEC tube formation in Matrigel, suggesting that reduction of miR-125a has a proangiogenic effect. In conclusion, downregulation of miR-125a through local transfection with miR-125a inhibitor might be a new way to enhance endothelial cell proliferation and viability, thereby promoting the reendothelialization observed in response to intimal injury. PMID- 25116895 TI - Dispacamide E and other bioactive bromopyrrole alkaloids from two Indonesian marine sponges of the genus Stylissa. AB - Chemical investigation of methanolic extracts of the two Indonesian marine sponges Stylissa massa and Stylissa flabelliformis yielded 25 bromopyrrole alkaloids including 2 new metabolites. The structures of all isolated compounds were unambiguously elucidated based on extensive 1D and 2D NMR, LR-MS and HR-MS analyses. All isolated compounds were assayed for their antiproliferative and protein kinase inhibitory activities. Several of the tested compounds revealed selective activity(ies) which suggested preliminary SARs of the isolated bromopyrrole alkaloids. PMID- 25116896 TI - Atypical resting synchrony in autism spectrum disorder. AB - Autism spectrum disorder (ASD) is increasingly understood to be associated with aberrant functional brain connectivity. Few studies, however, have described such atypical neural synchrony among specific brain regions. Here, we used magnetoencephalography (MEG) to characterize alterations in functional connectivity in adolescents with ASD through source space analysis of phase synchrony. Resting-state MEG data were collected from 16 adolescents with ASD and 15 age- and sex-matched typically developing (TD) adolescents. Atlas-guided reconstruction of neural activity at various cortical and subcortical regions was performed and inter-regional phase synchrony was calculated in physiologically relevant frequency bands. Using a multilevel approach, we characterized atypical resting-state synchrony within specific anatomically defined networks as well as altered network topologies at both regional and whole-network scales. Adolescents with ASD demonstrated frequency-dependent alterations in inter-regional functional connectivity. Hyperconnectivity was observed among the frontal, temporal, and subcortical regions in beta and gamma frequency ranges. In contrast, parietal and occipital regions were hypoconnected to widespread brain regions in theta and alpha bands in ASD. Furthermore, we isolated a hyperconnected network in the gamma band in adolescents with ASD which encompassed orbitofrontal, subcortical, and temporal regions implicated in social cognition. Results from graph analyses confirmed that frequency-dependent alterations of network topologies exist at both global and local levels. We present the first source-space investigation of oscillatory phase synchrony in resting-state MEG in ASD. This work provides evidence of atypical connectivity at physiologically relevant time scales and indicates that alterations of functional connectivity in adolescents with ASD are frequency dependent and region dependent. PMID- 25116897 TI - Contemporary patterns of discharge aspirin dosing after acute myocardial infarction in the United States: results from the National Cardiovascular Data Registry (NCDR). AB - BACKGROUND: Accumulated data suggest that low-dose aspirin after myocardial infarction (MI) may offer similar efficacy to higher dose aspirin with reduced risk of bleeding. Few data are available on contemporary aspirin dosing patterns after MI in the United States METHODS AND RESULTS: Aspirin dosing from 221 199 patients with MI (40.2% ST-segment-elevation MI) from 525 US hospitals enrolled in the National Cardiovascular Data Registry's (NCDR's) Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines were described, overall and in clinically relevant subgroups. High-dose aspirin was defined as 325 mg and low dose as 81 mg. Between January 2007 and March 2011, 60.9% of patients with acute MI were discharged on high-dose aspirin, 35.6% on low-dose aspirin, and 3.5% on other doses. High-dose aspirin was prescribed at discharge to 73.0% of patients treated with percutaneous coronary intervention and 44.6% of patients managed medically. Among 9075 patients discharged on aspirin, thienopyridine, and warfarin, 44.0% were prescribed high-dose aspirin. Patients with an in-hospital major bleeding event were also frequently discharged on high-dose aspirin (56.7%). A 25-fold variation in the proportion prescribed high-dose aspirin at discharge was observed across participating centers. CONCLUSIONS: Most US patients with MI continue to be discharged on high-dose aspirin. Although aspirin dosing after percutaneous coronary intervention largely reflected prevailing guidelines before 2012, high-dose aspirin was prescribed with similar frequency in medically managed patients and to those in categories expected to be at high risk for bleeding. Wide variability in the proportional use of high-dose aspirin across centers suggests significant influence from local practice habits and uncertainty about appropriate aspirin dosing. PMID- 25116898 TI - Examination of the treatment selection process in a multicenter observational study. AB - BACKGROUND: Many multicenter clinical trials use permuted-block randomization to create balanced treatment allocations within clinical centers. Unlike randomized trials, observational studies do not control treatment allocation, and statistical models are used to adjust for measured confounders. For many observational data analyses, the variability in the treatment selection process within clinical centers is ignored. Furthermore, there is no consensus on the best approach for dealing with variability in the treatment selection process across clinical centers. METHODS AND RESULTS: Individuals aged >=65 years receiving either drug-eluting stents or bare metal stents were included. A cohort of 262 700 patients from 650 CathPCI Registry sites was followed up for a median of 15 months. Propensity score models were estimated to describe the process used to select drug-eluting stents across the study population. Substantial variability in the use of drug-eluting stents at the clinical center level was observed-even after accounting for differences in patient and clinical center characteristics. By refitting and matching propensity scores within clinical centers, a balanced cohort on treatment allocation and prognostic factors was obtained. This approach generated an estimated hazard ratio that was qualitatively similar to standard regression models and other propensity score approaches. CONCLUSIONS: Substantial variability in treatment selection existed between clinical centers. Matching recalibrated propensity scores within clinical centers has the potential to reduce a source of bias in multicenter observational studies. This methodology cannot eliminate all potential for biases; however, it removes the potential bias from site-level factors. PMID- 25116899 TI - Trapping atmospheric CO2 with gold. AB - The ability of gold-hydroxides to fix CO2 is reported. [Au(IPr)(OH)] and [{Au(IPr)}2(MU-OH)][BF4] react with atmospheric CO2 to form the trigold carbonate complex [{Au(IPr)}3(MU(3)-CO3)][BF4]. Reactivity studies revealed that this complex behaves as two basic and one cationic Au centres, and that it is catalytically active. DFT calculations and kinetic experiments have been carried out. PMID- 25116894 TI - Three-dimensional in vitro tumor models for cancer research and drug evaluation. AB - Cancer occurs when cells acquire genomic instability and inflammation, produce abnormal levels of epigenetic factors/proteins and tumor suppressors, reprogram the energy metabolism and evade immune destruction, leading to the disruption of cell cycle/normal growth. An early event in carcinogenesis is loss of polarity and detachment from the natural basement membrane, allowing cells to form distinct three-dimensional (3D) structures that interact with each other and with the surrounding microenvironment. Although valuable information has been accumulated from traditional in vitro studies in which cells are grown on flat and hard plastic surfaces (2D culture), this culture condition does not reflect the essential features of tumor tissues. Further, fundamental understanding of cancer metastasis cannot be obtained readily from 2D studies because they lack the complex and dynamic cell-cell communications and cell-matrix interactions that occur during cancer metastasis. These shortcomings, along with lack of spatial depth and cell connectivity, limit the applicability of 2D cultures to accurate testing of pharmacologically active compounds, free or sequestered in nanoparticles. To recapitulate features of native tumor microenvironments, various biomimetic 3D tumor models have been developed to incorporate cancer and stromal cells, relevant matrix components, and biochemical and biophysical cues, into one spatially and temporally integrated system. In this article, we review recent advances in creating 3D tumor models employing tissue engineering principles. We then evaluate the utilities of these novel models for the testing of anticancer drugs and their delivery systems. We highlight the profound differences in responses from 3D in vitro tumors and conventional monolayer cultures. Overall, strategic integration of biological principles and engineering approaches will both improve understanding of tumor progression and invasion and support discovery of more personalized first line treatments for cancer patients. PMID- 25116901 TI - An ionizing radiation sensor using a pre-programmed MAHAOS device. AB - Metal-aluminum oxide-hafnium aluminum oxide-silicon oxide-silicon (hereafter MAHAOS) devices can be candidates for ionizing radiation sensor applications. In this work, MAHAOS devices (SONOS-like structures with high k stack gate dielectric) were studied regarding the first known characterization of the ionization radiation sensing response. The change of threshold voltage V(T) for a MAHAOS device after gamma ray exposure had a strong correlation to the total ionization dose (TID) of gamma radiation up to at least 5 Mrad TID. In this paper, the gamma radiation response performances of the pre-programmed and virgin (non-pre-programmed) MAHAOS devices are presented. The experimental data show that the change of VT for the pre-programmed MAHAOS device with gamma irradiation is very significant. The data of pre-programmed MAHAOS devices written by 5 Mrad TID of gamma radiation was also stable for a long time with data storage. The sensing of gamma radiation by pre-programmed MAHAOS devices with high k stack gate dielectric reported in this study has demonstrated their potential application for non-volatile ionizing radiation sensing technology in the future. PMID- 25116900 TI - The benefit of specialized team approaches in patients with acute kidney injury undergoing continuous renal replacement therapy: propensity score matched analysis. AB - INTRODUCTION: Continuous renal replacement therapy (CRRT) has been widely used in critically ill acute kidney injury (AKI) patients. Moreover, some centers operate a specialized CRRT team (SCT) composed of physicians and nurses, but few studies have yet determined the superiority of SCT control. METHODS: A total of 334 among 534 patients in the original cohort, who started CRRT for severe AKI between August 2007 and September 2009 in Yonsei University Health System and were matched with a propensity score (PS), were divided into two groups based on SCT application. Moreover, we compared CRRT-related outcomes including down-time per day and lost time per filter-exchange between the two groups. The primary outcomes were 28- and 90-day all-cause mortality, and the secondary outcomes were the rates of renal function recovery at 28- and 90-day. RESULTS: The down-time per day, lost time per filter-exchange, and red blood cell-transfused numbers during CRRT treatment were significantly lower after SCT approach compared with the group before SCT, while net ultrafiltration rate in the after SCT group was significantly higher compared to the before SCT group. During the study period, the 28- and 90-day all-cause mortality rates were significantly decreased after SCT application. Cox regression analysis revealed that 28- and 90-day all-cause mortality rates were significantly lower under SCT control, after adjusting for primary diagnosis, emergent surgical cases, Charlson Comorbidity Index and biochemical parameters. However, there were no significant differences in the rate of renal function recovery before and after SCT approach in CRRT. CONCLUSIONS: A well-organized CRRT team could be beneficial for clinical outcomes through improving quality of care in AKI patients requiring CRRT treatment in the ICU. PMID- 25116902 TI - LiftingWiSe: a lifting-based efficient data processing technique in wireless sensor networks. AB - Monitoring thousands of objects which are deployed over large-hard-to-reach areas, is an important application of the wireless sensor networks (WSNs). Such an application requires disseminating a large amount of data within the WSN. This data includes, but is not limited to, the object's location and the environment conditions at that location. WSNs require efficient data processing and dissemination processes due to the limited storage, processing power, and energy available in the WSN nodes. The aim of this paper is to propose a data processing technique that can work under constrained storage, processing, and energy resource conditions. The proposed technique utilizes the lifting procedure in processing the disseminated data. Lifting is usually used in discrete wavelet transform (DWT) operations. The proposed technique is referred to as LiftingWiSe, which stands for Lifting-based efficient data processing technique for Wireless Sensor Networks. LiftingWiSe has been tested and compared to other relevant techniques from the literature. The test has been conducted via a simulation of the monitored field and the deployed wireless sensor network nodes. The simulation results have been analyzed and discussed. PMID- 25116903 TI - Enhanced ethanol gas sensing properties of SnO2-core/ZnO-shell nanostructures. AB - An inexpensive single-step carbon-assisted thermal evaporation method for the growth of SnO2-core/ZnO-shell nanostructures is described, and the ethanol sensing properties are presented. The structure and phases of the grown nanostructures are investigated by field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) techniques. XRD analysis indicates that the core-shell nanostructures have good crystallinity. At a lower growth duration of 15 min, only SnO2 nanowires with a rectangular cross-section are observed, while the ZnO shell is observed when the growth time is increased to 30 min. Core-shell hierarchical nanostructures are present for a growth time exceeding 60 min. The growth mechanism for SnO2 core/ZnO-shell nanowires and hierarchical nanostructures are also discussed. The sensitivity of the synthesized SnO2-core/ZnO-shell nanostructures towards ethanol sensing is investigated. Results show that the SnO2-core/ZnO-shell nanostructures deposited at 90 min exhibit enhanced sensitivity to ethanol. The sensitivity of SnO2-core/ZnO-shell nanostructures towards 20 ppm ethanol gas at 400 degrees C is about ~5-times that of SnO2 nanowires. This improvement in ethanol gas response is attributed to high active sensing sites and the synergistic effect of the encapsulation of SnO2 by ZnO nanostructures. PMID- 25116905 TI - An energy-efficient and compact clustering scheme with temporary support nodes for cognitive radio sensor networks. AB - A cognitive radio sensor network (CRSN) is a wireless sensor network whose sensor nodes are equipped with cognitive radio capability. Clustering is one of the most challenging issues in CRSNs, as all sensor nodes, including the cluster head, have to use the same frequency band in order to form a cluster. However, due to the nature of heterogeneous channels in cognitive radio, it is difficult for sensor nodes to find a cluster head. This paper proposes a novel energy-efficient and compact clustering scheme named clustering with temporary support nodes (CENTRE). CENTRE efficiently achieves a compact cluster formation by adopting two phase cluster formation with fixed duration. By introducing a novel concept of temporary support nodes to improve the cluster formation, the proposed scheme enables sensor nodes in a network to find a cluster head efficiently. The performance study shows that not only is the clustering process efficient and compact but it also results in remarkable energy savings that prolong the overall network lifetime. In addition, the proposed scheme decreases both the clustering overhead and the average distance between cluster heads and their members. PMID- 25116904 TI - A review of brain-computer interface games and an opinion survey from researchers, developers and users. AB - In recent years, research on Brain-Computer Interface (BCI) technology for healthy users has attracted considerable interest, and BCI games are especially popular. This study reviews the current status of, and describes future directions, in the field of BCI games. To this end, we conducted a literature search and found that BCI control paradigms using electroencephalographic signals (motor imagery, P300, steady state visual evoked potential and passive approach reading mental state) have been the primary focus of research. We also conducted a survey of nearly three hundred participants that included researchers, game developers and users around the world. From this survey, we found that all three groups (researchers, developers and users) agreed on the significant influence and applicability of BCI and BCI games, and they all selected prostheses, rehabilitation and games as the most promising BCI applications. User and developer groups tended to give low priority to passive BCI and the whole head sensor array. Developers gave higher priorities to "the easiness of playing" and the "development platform" as important elements for BCI games and the market. Based on our assessment, we discuss the critical point at which BCI games will be able to progress from their current stage to widespread marketing to consumers. In conclusion, we propose three critical elements important for expansion of the BCI game market: standards, gameplay and appropriate integration. PMID- 25116906 TI - Warranty periods for normal myocardial perfusion stress SPECT. AB - BACKGROUND: To assess different warranty periods following a normal myocardial perfusion SPECT based on patients' clinical characteristics and the type of stress performed. METHODS AND RESULTS: A study was done of 2,922 consecutive patients (62.9 +/- 13 years; 53.4% women) with a normal stress-rest SPECT. The warranty period was defined as the period during which patients remained at a low risk (<1% events/year) of total mortality (TM), or hard events (HE) (cardiac death or non-fatal myocardial infarction). Of these patients, 2,051 were given an exercise myocardial perfusion imaging (Ex-MPI); 461 submaximal exercise plus dipyridamole (Ex+Dipy-MPI); and 410 dipyridamole (Dipy-MPI). During a mean follow up of 5 +/- 3.3 years, a significant reduction (P < .05) of the warranty period for TM (13.5, 9.6 and 8 months) and HE (34.8, 20.5 and 8.2 months) was observed, for Ex-MPI, Ex+Dipy-MPI and Dipy-MPI, respectively. Other warranty period determinants were the clinical variables of age, sex, diabetes and known coronary artery disease. An abnormal left ventricular ejection fraction on gated-SPECT also significantly shortened the warranty period for HE in patients undergoing Ex+Dipy-MPI (P = .001) or Dipy-MPI alone (P = .007). CONCLUSIONS: The warranty period for a normal stress-rest SPECT is highly variable since it is primarily determined by the type of stress, the patient's clinical characteristics and LVEF. PMID- 25116909 TI - Small molecules: from structural diversity to signalling and regulatory roles. PMID- 25116908 TI - Tai chi meditation effects on nuclear factor-kappaB signaling in lonely older adults: a randomized controlled trial. PMID- 25116910 TI - Topical calcium carbonate soda crystals for refractory cancer-related lower limb edema. PMID- 25116911 TI - What is different about patients with hematologic malignancies? A retrospective cohort study of cancer patients referred to a hospice research network. AB - CONTEXT: Although much is known about solid tumor patients who use hospice, the hematologic malignancies hospice population is inadequately described. OBJECTIVES: To compare the characteristics and outcomes of hospice patients with hematologic malignancies to those with solid tumors. METHODS: We extracted electronic patient data (2008-2012) from a large hospice network (Coalition of Hospices Organized to Investigate Comparative Effectiveness) and used bivariate analyses to describe between-group differences. RESULTS: In total, 48,147 patients with cancer were admitted during the study period; 3518 (7.3%) had a hematologic malignancy. These patients had significantly worse Palliative Performance Scale scores (32% vs. 24% were below 40; P < 0.001) and shorter lengths of stay (median 11 vs. 19 days; P < 0.001). They were more likely to die within 24 hours of hospice enrollment (10.9% vs. 6.8%; odds ratio [OR] 1.66; 95% CI 1.49, 1.86; P < 0.001) or within seven days (36% vs. 25.1%; OR 1.68; 95% CI 1.56, 1.81; P < 0.001) and were more likely to receive hospice services in an inpatient or nursing home setting (OR 1.34; 95% CI 1.16, 1.56 and OR 1.54; 95% CI 1.39, 1.72; both P < 0.001). Among hematologic malignancy patients, those with leukemia had the shortest survival (hazard ratio 1.23; 95% CI 1.13, 1.34; P < 0.001), and 40.3% used hospice for less than seven days (OR 1.31; 95% CI 1.11, 1.56; P = 0.002). CONCLUSION: Hospice patients with hematologic malignancies are more seriously ill at the time of admission, with worse functional status and shorter lengths of stay than other cancer patients. Differences in outcomes suggest the need for targeted interventions to optimize hospice services for the hematologic malignancies population, especially those with leukemia. PMID- 25116913 TI - Predictors of pursuit of physician-assisted death. AB - CONTEXT: Physician-assisted death (PAD) was legalized in 1997 by Oregon's Death with Dignity Act. The States of Washington, Montana, Vermont, and New Mexico have since provided legal sanction for PAD. Through 2013, 1173 Oregonians have received a prescription under the Death with Dignity Act and 752 have died after taking the prescribed medication in Oregon. OBJECTIVES: To determine the predictive value of personal and interpersonal variables in the pursuit of PAD. METHODS: Fifty-five Oregonians who either requested PAD or contacted a PAD advocacy organization were compared with 39 individuals with advanced disease who did not pursue PAD. We compared the two groups on responses to standardized measures of depression, hopelessness, spirituality, social support, and pain. We also compared the two groups on style of attachment to intimate others and caregivers as understood through attachment theory. RESULTS: We found that PAD requesters had higher levels of depression, hopelessness, and dismissive attachment (attachment to others characterized by independence and self reliance), and lower levels of spirituality. There were moderate correlations among the variables of spirituality, hopelessness, depression, social support, and dismissive attachment. There was a strong correlation between depression and hopelessness. Low spirituality emerged as the strongest predictor of pursuit of PAD in the regression analysis. CONCLUSION: Although some factors motivating pursuit of PAD, such as depression, may be ameliorated by medical interventions, other factors, such as style of attachment and sense of spirituality, are long standing aspects of the individual that should be supported at the end of life. Practitioners must develop respectful awareness and understanding of the interpersonal and spiritual perspectives of their patients to provide such support. PMID- 25116912 TI - Organization of nursing and quality of care for veterans at the end of life. AB - CONTEXT: The Veterans Health Administration (VA) has improved the quality of end of-life (EOL) care over the past several years. Several structural and process variables are associated with better outcomes. Little is known, however, about the relationship between the organization of nursing care and EOL outcomes. OBJECTIVES: To examine the association between the organization of nursing care, including the nurse work environment and nurse staffing levels, and quality of EOL care in VA acute care facilities. METHODS: Secondary analysis of linked data from the Bereaved Family Survey (BFS), electronic medical record, administrative data, and the VA Nursing Outcomes Database. The sample included 4908 veterans who died in one of 116 VA acute care facilities nationally between October 2010 and September 2011. Unadjusted and adjusted generalized estimating equations were used to examine associations between nursing and BFS outcomes. RESULTS: BFS respondents were 17% more likely to give an excellent overall rating of the quality of EOL care received by the veteran in facilities with better nurse work environments (P <= 0.05). The nurse work environment also was a significant predictor of providers listening to concerns and providing desired treatments. Nurse staffing was significantly associated with an excellent overall rating, alerting of the family before death, attention to personal care needs, and the provision of emotional support after the patient's death. CONCLUSION: Improvement of the nurse work environment and nurse staffing in VA acute care facilities may result in enhanced quality of care received by hospitalized veterans at the EOL. PMID- 25116915 TI - Alnuheptanoid A: a new diarylheptanoid derivative from Alnus japonica. AB - Extensive chromatographic investigation of the ethanolic extract of Alnus japonica Steud stem bark led to the isolation of a new diarylheptanoid named alnuheptanoid A [(5S)-7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-5-methoxyheptan 3-one] (8), together with seven known diarylheptanoid derivatives: platyphyllenone (5), (5S)-1,7-bis(4-hydroxyphenyl)-5-methoxyheptan-3-one (6), 1 (3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-4-hepten-3-one (7), hirsutenone (9), (5R)-O-methylhirsutanonol (10), hirsutanonol (11) and oregonin (13), three triterpenes: alpha-amyrin (1), betulinaldehyde (3) and betulinic acid (4), and two sterols: beta-sitosterol (2) and daucosterol (12). Compound 6 was isolated for the first time from natural source. The structures of the isolated compounds were determined on the basis of spectroscopic measurements (UV, IR, HR-ESI-MS, 1D and 2D NMR). PMID- 25116914 TI - Predictors of thirst in intensive care unit patients. AB - CONTEXT: Thirst is a pervasive, intense, and distressing symptom in intensive care unit (ICU) patients. Although thirst may be avoided and/or treated, scant data are available to help providers identify patients most in need. OBJECTIVES: This study was designed to identify predictors of the presence, intensity, and distress of thirst in ICU patients. METHODS: This descriptive cross-sectional study enrolled 353 patients from three ICUs (medical-surgical, cardiac, and neurological). To measure outcomes, patients were asked to report the presence of thirst (yes/no) and, if present, to rate its intensity and distress on zero to 10 numeric rating scales (10=worst). Predictor variables were demographic (e.g., age), treatment-related (e.g., opioids), and biological (e.g., total body water). Data were analyzed with logistic regression and truncated regression with alpha preset at 0.05. RESULTS: Thirst presence was predicted by high opioid doses (>= 50 mg), high furosemide doses (>60 mg), selective serotonin reuptake inhibitors, and low ionized calcium. Thirst intensity was predicted by patients not receiving oral fluid and having a gastrointestinal (GI) diagnosis. Thirst distress was predicted by mechanical ventilation, negative fluid balance, antihypertensive medications, and a GI or "other" diagnosis. CONCLUSION: Thirst presence was predicted by selected medications (e.g., opioids). Thirst intensity and/or thirst distress were predicted by other treatments (e.g., mechanical ventilation) and medical diagnoses (e.g., GI). This is one of the first studies describing predictors of the multidimensional characteristics of thirst. Clinicians can use these data to target ICU patients whose thirst might warrant treatment. PMID- 25116917 TI - Known knowns, known unknowns, unknown unknowns and unknown knowns in DNA barcoding: a comment on Dowton et al. PMID- 25116919 TI - A leaky membrane and a sodium transporter at life's great divergence. PMID- 25116916 TI - SILAC-based proteomic profiling of the human MDA-MB-231 metastatic breast cancer cell line in response to the two antitumoral lactoferrin isoforms: the secreted lactoferrin and the intracellular delta-lactoferrin. AB - BACKGROUND: Lactoferrins exhibit antitumoral activities either as a secretory lactoferrin or an intracellular delta-lactoferrin isoform. These activities involve processes such as regulation of the cell cycle and apoptosis. While lactoferrin has been shown to exert its function by activating different transduction pathways, delta-lactoferrin has been proven to act as a transcription factor. Like many tumor suppressors, these two proteins are under expressed in several types of cancer, particularly in breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to compare the differential effects of the re-introduction of lactoferrin isoforms in breast cancer cells we chose the cancerous mammary gland MDA-MB-231 cell line as a model. We produced a cell line stably expressing delta-lactoferrin. We also treated these cells with fresh purified human breast lactoferrin. We performed two quantitative proteomic studies in parallel using SILAC coupled to mass spectrometry in order to compare the effects of different doses of the two lactoferrin isoforms. The proteome of untreated, delta-lactoferrin expressing and human lactoferrin treated MDA-MB-231 cells were compared. Overall, around 5300 proteins were identified and quantified using the in-house developed MFPaQ software. Among these, expression was increased by 1.5-fold or more for around 300 proteins in delta-lactoferrin expressing cells and 190 proteins in lactoferrin treated cells. At the same time, about 200 and 40 proteins were found to be downregulated (0-0.7-fold) in response to delta-lactoferrin and lactoferrin, respectively. CONCLUSIONS/SIGNIFICANCE: Re introduction of delta-lactoferrin and lactoferrin expression in MDA-MB-231 mainly leads to modifications of protein profiles involved in processes such as proliferation, apoptosis, oxidative stress, the ubiquitin pathway, translation and mRNA quality control. Moreover, this study identified new target genes of delta-lactoferrin transcriptional activity such as SelH, GTF2F2 and UBE2E1. PMID- 25116920 TI - Otoacoustic emissions before and after listening to music on a personal player. AB - BACKGROUND: The problem of the potential impact of personal music players on the auditory system remains an open question. The purpose of the present study was to investigate, by means of otoacoustic emissions (OAEs), whether listening to music on a personal player affected auditory function. MATERIAL/METHODS: A group of 20 normally hearing adults was exposed to music played on a personal player. Transient evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs), as well as pure tone audiometry (PTA) thresholds, were tested at 3 stages: before, immediately after, and the next day following 30 min of exposure to music at 86.6 dBA. RESULTS: We found no statistically significant changes in OAE parameters or PTA thresholds due to listening to the music. CONCLUSIONS: These results suggest that exposure to music at levels similar to those used in our study does not disturb cochlear function in a way that can be detected by means of PTA, TEOAE, or DPOAE tests. PMID- 25116921 TI - Modeling luminal breast cancer heterogeneity: combination therapy to suppress a hormone receptor-negative, cytokeratin 5-positive subpopulation in luminal disease. AB - INTRODUCTION: Many Luminal breast cancers are heterogeneous, containing substantial numbers of estrogen (ER) and progesterone (PR) receptor-negative cells among the ER+ PR+ ones. One such subpopulation we call "Luminobasal" is ER , PR- and cytokeratin 5 (CK5)-positive. It is not targeted for treatment. METHODS: To address the relationships between ER+PR+CK5- and ER-PR-CK5+ cells in Luminal cancers and tightly control their ratios we generated isogenic pure Luminal (pLUM) and pure Luminobasal (pLB) cells from the same parental Luminal human breast cancer cell line. We used high-throughput screening to identify pLB specific drugs and examined their efficacy alone and in combination with hormone therapy in mixed-cell tumor models. RESULTS: We show that pLUM and MCF7 cells suppress proliferation of pLB cells in mixed-cell 3D colonies in vitro and that pLUM cells suppress growth of pLB cells in mixed-cell xenografts in vivo. High throughput screening of 89 FDA-approved oncology drugs shows that pLB cells are sensitive to monotherapy with the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib. By exploiting mixed-cell 3D colonies and mixed-cell solid mouse tumors models we demonstrate that combination therapy with gefitinib plus the anti-estrogen fulvestrant constitutes a robust treatment strategy. CONCLUSIONS: We propose that response to combination endocrine/EGFR inhibitor therapies in heterogeneous Luminal cancers may improve long-term survival in patients whose primary tumors have been preselected for appropriate biomarkers, including ER, PR, CK5 and EGFR. PMID- 25116930 TI - Characteristics of the orthostatic cardiovascular response in adolescent patients with psychogenic fever. PMID- 25116923 TI - English Longitudinal Study of Aging: can Internet/E-mail use reduce cognitive decline? AB - BACKGROUND: Cognitive decline is a major risk factor for disability, dementia, and death. The use of Internet/E-mail, also known as digital literacy, might decrease dementia incidence among the older population. The aim was to investigate whether digital literacy might be associated with decreased cognitive decline in older adulthood. METHODS: Data from the English Longitudinal Study of Aging cohort with 6,442 participants aged 50-89 years, followed for 8 years, with baseline cognitive testing and four additional time points. The main outcome variable was the relative percentage change in delayed recall from a 10-word-list learning task across five separate measurement points. In addition to digital literacy, socioeconomic variables, including wealth and education, comorbidities, and baseline cognitive function were included in predictive models. The analysis used Generalized Estimating Equations. RESULTS: Higher education, no functional impairment, fewer depressive symptoms, no diabetes, and Internet/E-mail use predicted better performance in delayed recall. CONCLUSIONS: Digital literacy may help reduce cognitive decline among persons aged between 50 and 89 years. PMID- 25116922 TI - New method for sperm evaluation by 3-dimensional laser scanning microscopy in different laboratory animal species. AB - Sperm analysis is one of the end points in reproductive toxicology studies. Different methods for quantitative sperm analysis have been described. For qualitative morphological sperm analysis, either such techniques or smears of sperm and histological sperm staging are in use. Any of these methods provides morphological results on a light microscopy level. Laser scanning microscopy is a technique using a focused laser for scanning an object. The Olympus 3D Laser Scanning Microscope LEXT OLS4000 with optional possibilities of differential interference contrast provides a microscopic method for visualizing microasperities, which are far beyond the resolving power of a typical light or laser microscope. This technique was applied to sperm of mice, rats, rabbits, and cynomolgus monkeys at magnifications up to *17 090. The obtained images are comparable to those of a scanning electron microscope under relatively low-power magnifications. Measurements on sperm parameters were taken by an integrated image analysis software tool. Abnormalities were easily detectable. PMID- 25116931 TI - Expression of vesicular glutamate transporter 3 mRNA in the brain and retina of the pigeon. AB - Vesicular glutamate transporters (vGluTs), which accumulate glutamate into synaptic vesicles, are classified into three subtypes in mammalian brains: vGluT1, vGluT2, and vGluT3. VGluT3 is localized in non-glutamatergic neurons of the brain and retinal amacrine cells. In birds, the vGluT3 genome is found, but its distribution in the brain or retina is unknown. The present study was conducted to analyze vGluT3 cDNA sequence and elucidate its distribution in the pigeon brain and retina. The vGluT3 cDNA comprises 1761bp and showed 95% and 88% identity to the chicken and zebra finch vGluT3 cDNAs, respectively, and 74% identity to human vGluT3 cDNA. In situ hybridization revealed that the vGluT3 mRNA was expressed in neurons of the caudal linear nucleus (LC) of the brain and in amacrine cells of the inner nuclear layer of the retina. A combination of in situ hybridization and serotonin immunohistochemistry revealed three types of stained cells in LC and retina: vGluT3(+)/serotonin(+), vGluT3(+)/serotonin(-), and vGluT3(-)/serotonin(+). The vGluT3(+)/serotonin(+) cells were approximately 22% in LC and 16% in the retina. The present results suggest that the pigeon vGluT3 mRNA is comparable with the mammalian type. PMID- 25116934 TI - Acute testicular fracture. PMID- 25116935 TI - Different childhood adversities are associated with different symptom patterns in adulthood. PMID- 25116933 TI - Evaluation of functional genetic variants at 6q25.1 and risk of breast cancer in a Chinese population. AB - INTRODUCTION: Single-nucleotide polymorphisms (SNPs) at 6q25.1 that are associated with breast cancer susceptibility have been identified in several genome-wide association studies (GWASs). However, the exact causal variants in this region have not been clarified. METHODS: In the present study, we genotyped six potentially functional single-nucleotide polymorphisms (SNPs) within the CCDC170 and ESR1 gene regions at 6q25.1 and accessed their associations with risk of breast cancer in a study of 1,064 cases and 1,073 cancer-free controls in Chinese women. The biological function of the risk variant was further evaluated by performing laboratory experiments. RESULTS: Breast cancer risk was significantly associated with three SNPs located at 6q25.1-rs9383935 in CCDC170 and rs2228480 and rs3798758 in ESR1-with variant allele attributed odds ratios (ORs) of 1.38 (95% confidence interval (CI): 1.20 to 1.57, P=2.21*10(-6)), 0.84 (95% CI: 0.72 to 0.98, P=0.025) and 1.19 (95% CI: 1.04 to 1.37, P=0.013), respectively. The functional variant rs9383935 is in high linkage disequilibrium (LD) with GWAS-reported top-hit SNP (rs2046210), but only rs9383935 showed a strong independent effect in conditional regression analysis. The rs9383935 risk allele A showed decreased activity of reporter gene in both the MCF-7 and BT-474 breast cancer cell lines, which might be due to an altered binding capacity of miR-27a to the 3' untranslated region (3' UTR) sequence of CCDC170. Real-time quantitative reverse transcription PCR confirmed the correlation between rs9383935 genotypes and CCDC170 expression levels. CONCLUSIONS: The results of this study suggest that the functional variant rs9383935, located at the 3' UTR of CCDC170, may be one candidate of the causal variants at 6q25.1 that modulate the risk of breast cancer. PMID- 25116936 TI - Does the majority always know best? Young children's flexible trust in majority opinion. AB - Copying the majority is generally an adaptive social learning strategy but the majority does not always know best. Previous work has demonstrated young children's selective uptake of information from a consensus over a lone dissenter. The current study examined children's flexibility in following the majority: do they overextend their reliance on this heuristic to situations where the dissenting individual has privileged knowledge and should be trusted instead? Four- to six- year-olds (N = 103) heard conflicting claims about the identity of hidden drawings from a majority and a dissenter in two between-subject conditions: in one, the dissenter had privileged knowledge over the majority (he drew the pictures); in the other he did not (they were drawn by an absent third party). Overall, children were less likely to trust the majority in the Privileged Dissenter condition. Moreover, 5- and 6- year-olds made majority-based inferences when the dissenter had no privileged knowledge but systematically endorsed the dissenter when he drew the pictures. The current findings suggest that by 5 years, children are able to make an epistemic-based judgment to decide whether or not to follow the majority rather than automatically following the most common view. PMID- 25116937 TI - Value of water mazes for assessing spatial and egocentric learning and memory in rodent basic research and regulatory studies. AB - Maneuvering safely through the environment is central to survival of all animals. The ability to do this depends on learning and remembering locations. This capacity is encoded in the brain by two systems: one using cues outside the organism (distal cues), allocentric navigation, and one using self-movement, internal cues and sometimes proximal cues, egocentric navigation. Allocentric navigation involves the hippocampus, entorhinal cortex, and surrounding structures (e.g., subiculum); in humans this system encodes declarative memory (allocentric, semantic, and episodic, i.e., memory for people, places, things, and events). This form of memory is assessed in laboratory animals by many methods, but predominantly the Morris water maze (MWM). Egocentric navigation involves the dorsal striatum and connected structures; in humans this system encodes routes and integrated paths and when over-learned becomes implicit or procedural memory. Several allocentric methods for rodents are reviewed and compared with the MWM with particular focus on the Cincinnati water maze (CWM). MWM advantages include minimal training, no food deprivation, ease of testing, reliable learning, insensitivity to differences in body weight and appetite, absence of non-performers, control methods for performance effects, repeated testing capability and other factors that make this test well-suited for regulatory studies. MWM limitations are also reviewed. Evidence-based MWM design and testing methods are presented. On balance, the MWM is arguably the preferred test for assessing learning and memory in basic research and regulatory studies and the CWM is recommended if two tests can be accommodated so that both allocentric (MWM) and egocentric (CWM) learning and memory can be effectively and efficiently assessed. PMID- 25116938 TI - Preferences for the delivery of community pharmacy services to help manage chronic conditions. AB - BACKGROUND: To optimize positive outcomes, the design of new pharmacy services should consider the preferences of consumers with chronic condition(s) and their carers. OBJECTIVES: (i) To evaluate the relative importance of community pharmacy service characteristics, from the perspective of consumers with chronic condition(s) and carers; (ii) To compare consumer and carer preferences to health professional beliefs about ideal service characteristics for consumers. METHOD: A discrete choice experiment was completed by consumers with chronic condition(s) and/or carers (n = 602) and health professionals (n = 297), recruited from four regions in Australia. Participants were each randomized to one survey version containing four (from a total 72) different choices between two new pharmacy services. Consumer and carer participants were also given an 'opt out' alternative of current service. Each service was described using six attributes related to pharmacy service characteristics: continued medicines supply, continuity and coordinated care, location, medication management, education and information, and cost. RESULTS: Consumers and carers placed highest priority on continued medicines supply by a pharmacist for regular and symptom flare up medicines (100 priority points), a pharmacy located within a 'one-stop' health center (61 points) and home delivery of medicines (52 points). Although continued medicines supply was most important for consumers and carers, pharmacy location was perceived by health professionals to be the most important characteristic for consumers. Participants were less inclined to choose new services if their current pharmacy offered high quality services that were person-centered, easy to access and responsive to their needs. Younger, more highly educated and employed participants, and those with established condition(s) were more likely to choose new services. CONCLUSIONS: Person-centered care is a fundamental tenet for pharmacy services. The provision of continued medicines supply (e.g. through pharmacist prescribing), convenient and coordinated care delivered through a one stop health centre, and home delivery of medicines, should be prioritized when planning pharmacy services to best assist consumers to manage chronic conditions. PMID- 25116940 TI - The effects of alloying and segregation for the reactivity and diffusion of oxygen on Cu3Au(111). AB - We report results of the segregation induced by the adsorption of O2 and the barrier of the formation of Cu2O in Cu3Au(111) with an experimental and theoretical approach. Oxidation by a hyperthermal O2 molecular beam (HOMB) was investigated by X-ray photoemission spectroscopy in conjunction with a synchrotron light source. From the incident-energy dependence of the measured O uptake curve, dissociative adsorption of O2 is less effective on Cu3Au(111) than on Cu(111). The dissociative adsorption is accompanied by the Cu segregation on Cu3Au(111) as well as on Cu3Au(100) and Cu3Au(110). The obvious growth of Cu2O for a 2.3 eV HOMB cannot be observed and it suggests that the Au-rich protective layers prevent the diffusion of O atoms into the bulk. The theoretical approach based on density functional theory indicates that O adsorption shows the same behavior on Cu3Au(111) and on Cu(111). For the diffusion case, the barrier to diffuse into the subsurface in segregated Cu3Au(111) is higher than in Cu(111). This indicates that the segregated Au-rich layer in Cu3Au(111) works as a protective layer. PMID- 25116941 TI - Physical therapy in multiple sclerosis differs across Europe: information regarding an ongoing study. PMID- 25116939 TI - Crossover localisation is regulated by the neddylation posttranslational regulatory pathway. AB - Crossovers (COs) are at the origin of genetic variability, occurring across successive generations, and they are also essential for the correct segregation of chromosomes during meiosis. Their number and position are precisely controlled, however the mechanisms underlying these controls are poorly understood. Neddylation/rubylation is a regulatory pathway of posttranslational protein modification that is required for numerous cellular processes in eukaryotes, but has not yet been linked to homologous recombination. In a screen for meiotic recombination-defective mutants, we identified several axr1 alleles, disrupting the gene encoding the E1 enzyme of the neddylation complex in Arabidopsis. Using genetic and cytological approaches we found that axr1 mutants are characterised by a shortage in bivalent formation correlated with strong synapsis defects. We determined that the bivalent shortage in axr1 is not due to a general decrease in CO formation but rather due to a mislocalisation of class I COs. In axr1, as in wild type, COs are still under the control of the ZMM group of proteins. However, in contrast to wild type, they tend to cluster together and no longer follow the obligatory CO rule. Lastly, we showed that this deregulation of CO localisation is likely to be mediated by the activity of a cullin 4 RING ligase, known to be involved in DNA damage sensing during somatic DNA repair and mouse spermatogenesis. In conclusion, we provide evidence that the neddylation/rubylation pathway of protein modification is a key regulator of meiotic recombination. We propose that rather than regulating the number of recombination events, this pathway regulates their localisation, through the activation of cullin 4 RING ligase complexes. Possible targets for these ligases are discussed. PMID- 25116944 TI - Simultaneous imaging of both product ions: exploring gateway states for HCl as a benchmark molecule. AB - Simultaneous imaging of both positive and negative product ions is used to exclusively study photoion pair formation free from interference of competing fragmentation channels. Resonance enhanced multi-photon excitation allows us to interrogate potential energy surfaces for vastly differing molecular geometries. 3D imaging provides complete fragment information. We applied the technique to HCl as a benchmark and identified the gateway state leading to photoion pairs. The approach can easily be applied to any molecule exhibiting a potential with an attractive part at large internuclear distances. PMID- 25116945 TI - Childhood maltreatment and somatic complaints among adult psychiatric outpatients: exploring the mediating role of alexithymia. PMID- 25116943 TI - Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer. AB - BACKGROUND: Long intergenic non-coding RNAs (lncRNAs) represent an emerging and under-studied class of transcripts that play a significant role in human cancers. Due to the tissue- and cancer-specific expression patterns observed for many lncRNAs it is believed that they could serve as ideal diagnostic biomarkers. However, until each tumor type is examined more closely, many of these lncRNAs will remain elusive. RESULTS: Here we characterize the lncRNA landscape in lung cancer using publicly available transcriptome sequencing data from a cohort of 567 adenocarcinoma and squamous cell carcinoma tumors. Through this compendium we identify over 3,000 unannotated intergenic transcripts representing novel lncRNAs. Through comparison of both adenocarcinoma and squamous cell carcinomas with matched controls we discover 111 differentially expressed lncRNAs, which we term lung cancer-associated lncRNAs (LCALs). A pan-cancer analysis of 324 additional tumor and adjacent normal pairs enable us to identify a subset of lncRNAs that display enriched expression specific to lung cancer as well as a subset that appear to be broadly deregulated across human cancers. Integration of exome sequencing data reveals that expression levels of many LCALs have significant associations with the mutational status of key oncogenes in lung cancer. Functional validation, using both knockdown and overexpression, shows that the most differentially expressed lncRNA, LCAL1, plays a role in cellular proliferation. CONCLUSIONS: Our systematic characterization of publicly available transcriptome data provides the foundation for future efforts to understand the role of LCALs, develop novel biomarkers, and improve knowledge of lung tumor biology. PMID- 25116946 TI - Perspectives of the antipsoriatic heliotherapy in Poland. AB - Statistical analysis of the daily course of exposures to TL-01 tube radiation for 93 psoriatic patients from the Medical University of Lodz during 20-day phototherapy shows that the dose of 1 J/cm(2) represents a unit of single exposure necessary for psoriasis healing. This value is converted to the antipsoriatic effective dose of 317.9 J/m(2) using the TL-01 lamp irradiance spectrum and the antipsoriatic action spectrum. It is proposed that the daily exposure of 317.9 J/m(2) serves as the standard antipsoriatic dose (SAPD) providing a link between the cabinet and the out-door exposures and it could be used for planning heliotherapy in Poland. A model is proposed to calculate ambient antipsoriatic doses for 3 h exposures around the local noon (9 am-12 am GMT) based on satellite measurements of ozone and cloud characteristics. The model constants are determined by a comparison with pertaining antipsoriatic doses measured by the Brewer spectrophotometer in central Poland. It is found that 3 h exposures to solar radiation in the period 15 May-15 September provides the mean (2005-2013) doses in the range 2.7-3.1 SAPD over Poland. Thus, heliotherapy could be treated as an alternative to the cabinet phototherapy for almost 4 months. It seems that the most effective site for antipsoriatic heliotherapy is the south/east part of Poland (the Bieszczady Mountains). The heliotherapy could be carried out in existing national health centers equipped with the standard easy-to-use biometers for on-line monitoring of UV level and controlling duration of sunbathing to avoid erythema risks. It is even possible to control the antipsoriatic heliotherapy by a patient himself, using low-cost hand-held instruments measuring UV index. PMID- 25116947 TI - Influence of external, intrinsic and individual behaviour variables on serum 25(OH)D in a German survey. AB - The objective of the present study was to identify external, intrinsic or behavioural factors that significantly influenced serum 25-hydroxyvitamin D (25(OH)D) concentrations in a German survey. Data from 3061 participants in the Cooperative Health Research in the Region of Augsburg, Germany (KORA) F4 survey were used to relate potential determinants to measured mean serum 25(OH)D concentrations using multivariable regression models. The factors significantly associated with hypovitaminosis D (defined as 25(OH)D<25 nmolL(-1)) were season (winter, spring and autumn), urban environment and high body mass index. In contrast, times spent in sunny regions, hours per day spent outdoors in the summer as well as additional oral intake were associated with higher 25(OH)D concentrations. These results suggest that mainly ambient UV exposure but also individual behaviour are the most important determinants for personal 25(OH)D concentrations. The analyses further showed that in winter 43% of subjects were vitamin D deficient and 42% insufficient. Even in summer over half the population has insufficient vitamin D status with 8% deficient and 47% insufficient. Therefore measures to mitigate widespread vitamin D insufficiency such as regular short-term sun exposure and/or improved dietary intake/supplementation recommendations by public health bodies need to be considered. PMID- 25116948 TI - Green synthesis of gold nanoparticles for staining human cervical cancer cells and DNA binding assay. AB - Gold nanoparticles have been functionalized by non-ionic surfactants (polysorbates) used in pharmaceutical formulations. This results in the formation of more well-dispersed gold nanoparticles (GNPs) than the GNPs formed in neat water. The synthesized GNPs show good temporal stability. The synthesis conditions are mild and environmentally benign. The GNPs can bind to ct-DNA and displace bound dye molecules. The DNA-binding assay is significant as it preliminarily indicated that DNA-GNP conjugates can be formed. Such conjugates are extremely promising for applications in nanobiotechnology. The GNPs can also stain the human cervical cancer (HeLa) cells over a wide concentration range while remaining non-cytotoxic, thus providing a non invasive cell staining method. This result is very promising as we observe staining of HeLa cells at very low GNP concentrations (1 MUM) while the cell viability is retained even at 10-fold higher GNP concentrations. PMID- 25116949 TI - GFS9/TT9 contributes to intracellular membrane trafficking and flavonoid accumulation in Arabidopsis thaliana. AB - Flavonoids are the most important pigments for the coloration of flowers and seeds. In plant cells, flavonoids are synthesized by a multi-enzyme complex located on the cytosolic surface of the endoplasmic reticulum, and they accumulate in vacuoles. Two non-exclusive pathways have been proposed to mediate flavonoid transport to vacuoles: the membrane transporter-mediated pathway and the vesicle trafficking-mediated pathway. No molecules involved in the vesicle trafficking-mediated pathway have been identified, however. Here, we show that a membrane trafficking factor, GFS9, has a role in flavonoid accumulation in the vacuole. We screened a library of Arabidopsis thaliana mutants with defects in vesicle trafficking, and isolated the gfs9 mutant with abnormal pale tan-colored seeds caused by low flavonoid accumulation levels. gfs9 is allelic to the unidentified transparent testa mutant tt9. The responsible gene for these phenotypes encodes a previously uncharacterized protein containing a region that is conserved among eukaryotes. GFS9 is a peripheral membrane protein localized at the Golgi apparatus. GFS9 deficiency causes several membrane trafficking defects, including the mis-sorting of vacuolar proteins, vacuole fragmentation, the aggregation of enlarged vesicles, and the proliferation of autophagosome-like structures. These results suggest that GFS9 is required for vacuolar development through membrane fusion at vacuoles. Our findings introduce a concept that plants use GFS9-mediated membrane trafficking machinery for delivery of not only proteins but also phytochemicals, such as flavonoids, to vacuoles. PMID- 25116951 TI - Post-translational modifications of integrin ligands as pathogenic mechanisms in disease. AB - Protein post-translational modifications like glycation, carbamylation and citrullination increase the functional diversity of the proteome but in disease situations might do more harm than good. Post-translational modifications of ECM proteins are thus appearing as mechanisms, which contribute to tissue dysfunction in chronic kidney disease, in diabetes and in various inflammatory diseases. In chronic renal failure, carbamylation could lead to kidney fibrosis. In diabetes, high glucose levels lead to non-enzymatic glycation and cross-linking of collagens, which contribute to tissue stiffening with consequences for cardiovascular and renal functions. In inflammatory diseases, citrullination deiminates arginine residues with possible consequences for integrin-mediated cell adhesion to RGD- and GFOGER sequences in ECM proteins. Citrullination of fibronectin was in one study suggested to affect cell adhesion by modifying the heparin-binding site and not the RGD site. In a recent publication citrullination of GFOGER sequences in collagen II was demonstrated to selectively affect alpha10beta1 and alpha11beta1 integrin-mediated cell adhesion to collagen II, with consequences for synovial fibroblast and stem cell adhesion and migration. The implications of citrullination affecting integrin binding in disease open up a new area of study and might have implications for the pathogenesis of inflammatory diseases like rheumatoid arthritis and periodontitis. PMID- 25116953 TI - TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium. AB - Toll-like receptor 4 (TLR4) is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4 induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA), a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody, suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO) inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells induced by KLA were markedly attenuated. Moreover, KLA increased the expression of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these processes. In in vivo studies, KLA increased monocyte adhesion to aortic endothelium of wild-type (WT) mice, which was attenuated in WT mice treated with anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4 mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis. PMID- 25116955 TI - Battle of the bulge: the yin and yang of vascular endothelial growth factor in obesity. PMID- 25116954 TI - Antiangiogenic actions of vascular endothelial growth factor-A165b, an inhibitory isoform of vascular endothelial growth factor-A, in human obesity. AB - BACKGROUND: Experimental studies suggest that visceral adiposity and adipose tissue dysfunction play a central role in obesity-related cardiometabolic complications. Impaired angiogenesis in fat has been implicated in the development of adipose tissue hypoxia, capillary rarefaction, inflammation, and metabolic dysregulation, but pathophysiological mechanisms remain unknown. In this study, we examined the role of a novel antiangiogenic isoform of vascular endothelial growth factor-A (VEGF-A), VEGF-A165b, in human obesity. METHODS AND RESULTS: We biopsied paired subcutaneous and visceral adipose tissue in 40 obese subjects (body mass index, 45+/-8 kg/m(2); age, 45+/-11 years) during bariatric surgery and characterized depot-specific adipose tissue angiogenic capacity using an established ex vivo assay. Visceral adipose tissue exhibited significantly blunted angiogenic growth compared with subcutaneous fat (P<0.001) that was associated with marked tissue upregulation of VEGF-A165b (P=0.004). The extent of VEGF-A165b expression correlated negatively with angiogenic growth (r=-0.6, P=0.006). Although recombinant VEGF-A165b significantly impaired angiogenesis, targeted inhibition of VEGF-A165b with neutralizing antibody stimulated fat pad neovascularization and restored VEGF receptor activation. Blood levels of VEGF A165b were significantly higher in obese subjects compared with lean control subjects (P=0.02), and surgical weight loss induced a marked decline in serumVEGF A165b (P=0.003). CONCLUSIONS: We demonstrate that impaired adipose tissue angiogenesis is associated with overexpression of a novel antiangiogenic factor, VEGF-A165b, that may play a pathogenic role in human adiposopathy. Moreover, systemic upregulation of VEGF-A165b in circulating blood may have wider-ranging implications beyond the adipose milieu. VEGF-A165b may represent a novel area of investigation to gain further understanding of mechanisms that modulate the cardiometabolic consequences of obesity. PMID- 25116958 TI - Analyte interactions with a new ditopic dansylamide-nitrobenzoxadiazole dyad: a combined photophysical, NMR, and theoretical (DFT) study. AB - We report herein the synthesis and photophysical studies on a new multicomponent chemosensor dyad comprising two fluorescing units, dansylamide (DANS) and nitrobenzoxadiazole (NBD). The system has been developed to investigate receptor analyte binding interactions in the presence of both cations and anions in a single molecular system. A dimethyl amino (in the DANS unit) group is used as a receptor for cations, and acidic hydrogens of sulfonamide and the NBD group are used as receptors for anions. The system is characterized by conventional analytical techniques. The photophysical properties of this supramolecular system in the absence and presence of various metal ions and nonmetal ions as additives are investigated in an acetonitrile medium. Utility of this system in an aqueous medium has also been demonstrated. The absorption and fluorescence spectrum of the molecular system consists of a broad band typical of an intramolecular charge transfer (ICT) transition. A low quantum yield and lifetime of the NBD moiety in the present dyad indicates photoinduced electron transfer (PET) between DANS and the NBD moiety. The fluorescence intensity of the system is found to decrease in the presence of fluoride and acetate anions; however, the quenching is found to be much higher for fluoride. This quenching behavior is attributed to the enhanced PET from the anion receptor to the fluorophore moiety. The mechanistic aspect of the fluoride ion signaling behavior has also been studied by infrared (IR) and (1)H NMR experiments. The hydrogen bonding interaction between the acidic NH protons of the DPN moiety and F(-) is found to be primarily responsible for the fluoride selective signaling behavior. While investigating the cation signaling behavior, contrary to anions, significant fluorescence enhancement has been observed only in the presence of transition-metal ions. This behavior is rationalized by considering the disruption of PET communication between DANS and the NBD moiety due to transition-metal ion binding. Theoretical (density functional theory) studies are also performed for the better understanding of the receptor-analyte interaction. Interestingly, negative cooperativity in binding is observed when the interaction of this system is studied in the presence of both Zn(2+) and F(-). Fluorescence microscopy studies also revealed that the newly developed fluorescent sensor system can be employed as an imaging probe in live cells. PMID- 25116959 TI - alpha-Glucosidase inhibitory activity of marine sponges collected in Mauritius waters. AB - This report describes the use of alpha-glucosidase to evaluate the anti-diabetic potential of extracts from marine sponges collected in the Mauritius waters. Initial screening at 1.0 mg/mL of 141 extracts obtained from 47 sponge species revealed 10 extracts with inhibitory activity greater than 85%. Seven of the 10 extracts were further tested at 0.1 and 0.01 mg/mL and only the methanol extract of two sponges namely Acanthostylotella sp. (ASSM) and Echinodictyum pykei (EPM) showed inhibition activity greater than 60% at 0.1 mg/mL with an IC50 value of 0.16 +/- 0.02 and 0.04 +/- 0.01 mg/mL, respectively, while being inactive at 0.01 mg/mL. PMID- 25116957 TI - Adaptive evolution and environmental durability jointly structure phylodynamic patterns in avian influenza viruses. AB - Avian influenza viruses (AIVs) have been pivotal to the origination of human pandemic strains. Despite their scientific and public health significance, however, there remains much to be understood about the ecology and evolution of AIVs in wild birds, where major pools of genetic diversity are generated and maintained. Here, we present comparative phylodynamic analyses of human and AIVs in North America, demonstrating (i) significantly higher standing genetic diversity and (ii) phylogenetic trees with a weaker signature of immune escape in AIVs than in human viruses. To explain these differences, we performed statistical analyses to quantify the relative contribution of several potential explanations. We found that HA genetic diversity in avian viruses is determined by a combination of factors, predominantly subtype-specific differences in host immune selective pressure and the ecology of transmission (in particular, the durability of subtypes in aquatic environments). Extending this analysis using a computational model demonstrated that virus durability may lead to long-term, indirect chains of transmission that, when coupled with a short host lifespan, can generate and maintain the observed high levels of genetic diversity. Further evidence in support of this novel finding was found by demonstrating an association between subtype-specific environmental durability and predicted phylogenetic signatures: genetic diversity, variation in phylogenetic tree branch lengths, and tree height. The conclusion that environmental transmission plays an important role in the evolutionary biology of avian influenza viruses-a manifestation of the "storage effect"-highlights the potentially unpredictable impact of wildlife reservoirs for future human pandemics and the need for improved understanding of the natural ecology of these viruses. PMID- 25116956 TI - Alternatively spliced tissue factor promotes plaque angiogenesis through the activation of hypoxia-inducible factor-1alpha and vascular endothelial growth factor signaling. AB - BACKGROUND: Alternatively spliced tissue factor (asTF) is a novel isoform of full length tissue factor, which exhibits angiogenic activity. Although asTF has been detected in human plaques, it is unknown whether its expression in atherosclerosis causes increased neovascularization and an advanced plaque phenotype. METHODS AND RESULTS: Carotid (n=10) and coronary (n=8) specimens from patients with stable or unstable angina were classified as complicated or uncomplicated on the basis of plaque morphology. Analysis of asTF expression and cell type-specific expression revealed a strong expression and colocalization of asTF with macrophages and neovessels within complicated, but not uncomplicated, human plaques. Our results showed that the angiogenic activity of asTF is mediated via hypoxia-inducible factor-1alpha upregulation through integrins and activation of phosphatidylinositol-3-kinase/Akt and mitogen-activated protein kinase pathways. Hypoxia-inducible factor-1alpha upregulation by asTF also was associated with increased vascular endothelial growth factor expression in primary human endothelial cells, and vascular endothelial growth factor-Trap significantly reduced the angiogenic effect of asTF in vivo. Furthermore, asTF gene transfer significantly increased neointima formation and neovascularization after carotid wire injury in ApoE(-/-) mice. CONCLUSIONS: The results of this study provide strong evidence that asTF promotes neointima formation and angiogenesis in an experimental model of accelerated atherosclerosis. Here, we demonstrate that the angiogenic effect of asTF is mediated via the activation of the hypoxia-inducible factor-1/vascular endothelial growth factor signaling. This mechanism may be relevant to neovascularization and the progression and associated complications of human atherosclerosis as suggested by the increased expression of asTF in complicated versus uncomplicated human carotid and coronary plaques. PMID- 25116960 TI - Lack of depotentiation at basal ganglia output neurons in PD patients with levodopa-induced dyskinesia. AB - Parkinson's disease (PD), characterized by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease which produces bradykinesia, rigidity, tremor and postural instability. The dopamine precursor levodopa (L-Dopa) is the most effective treatment for the amelioration of PD signs and symptoms, but long-term administration can lead to disabling motor fluctuations and L-Dopa-induced dyskinesias. In animal models of PD, a form of plasticity called depotentiation, or the reversal of previous potentiation, is selectively lost after the development of dyskinetic movements following L-Dopa treatment. We investigated whether low frequency stimulation (LFS) in the globus pallidus internus (GPi) and substantia nigra pars reticulata (SNr) could induce depotentiation at synapses that had already undergone high frequency stimulation (HFS)-induced potentiation. To do so, we measured the field potentials (fEPs) evoked by stimulation from a nearby microelectrode in 28 patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN) or GPi. We found that GPi and SNr synapses in patients with less severe dyskinesia underwent greater depotentiation following LFS than in patients with more severe dyskinesia. This demonstration of impaired depotentiation in basal ganglia output nuclei in PD patients with dyskinesia is an important validation of animal models of levodopa-induced dyskinesia. The ability of a synapse to reverse previous potentiation may be crucial to the normal function of the BG, perhaps by preventing saturation of the storage capacity required in motor learning and optimal motor function. Loss of this ability at the output nuclei may underlie, or contribute to the cellular basis of dyskinetic movements. PMID- 25116962 TI - Psoriasis: the new and the old. PMID- 25116961 TI - Expression patterns of sex-determination genes in single male and female embryos of two Bactrocera fruit fly species during early development. AB - In tephritids, the sex-determination pathway follows the sex-specific splicing of transformer (tra) mRNA, and the cooperation of tra and transformer-2 (tra-2) to effect the sex-specific splicing of doublesex (dsx), the genetic double-switch responsible for male or female somatic development. The Dominant Male Determiner (M) is the primary signal that controls this pathway. M, as yet uncharacterized, is Y-chromosome linked, expressed in the zygote and directly or indirectly diminishes active TRA protein in male embryos. Here we first demonstrated the high conservation of tra, tra-2 and dsx in two Australian tephritids, Bactrocera tryoni and Bactrocera jarvisi. We then used quantitative reverse transcription PCR on single, sexed embryos to examine expression of the key sex-determination genes during early embryogenesis. Individual embryos were sexed using molecular markers located on the B. jarvisi Y-chromosome that was also introgressed into a B. tryoni line. In B. jarvisi, sex-specific expression of tra transcripts occurred between 3 to 6 h after egg laying, and the dsx isoform was established by 7 h. These milestones were delayed in B. tryoni lines. The results provide a time frame for transcriptomic analyses to identify M and its direct targets, plus information on genes that may be targeted for the development of male-only lines for pest management. PMID- 25116963 TI - Therapeutic update on hyperhidrosis. PMID- 25116964 TI - Sorafenib-associated psoriasiform eruption in a patient with hepatocellular carcinoma. PMID- 25116965 TI - Dramatic clearance of HIV-associated bowenoid papulosis using combined oral acitretin and topical 5% imiquimod. PMID- 25116966 TI - Ustekinumab treatment for psoriasis in 119 patients maintained on therapy for a minimum of one year: a review. AB - Ustekinumab is a human IgG1kappa monoclonal antibody that binds with high affinity and specificity to the p40 protein subunit shared by both the interleukin-12 and interleukin-23 cytokines. This study reviews clinical response and adverse events in 119 psoriasis patients who have received ustekinumab for a minimum of 1 year. The medical records of 119 psoriasis patients treated with ustekinumab at our referral clinic in Dallas between 2009 and 2013 were reviewed for response rates, side effects, and concomitant therapies. Of 119 patients, 117 (98%) had plaque type psoriasis, with 40 (34%) patients having psoriasis affecting either their palms and/or soles. Forty-four (37%) patients had psoriatic arthritis. The median follow-up period was 31 months. Fifty-six (47%) of the 119 patients obtained near complete clearance (response of more than 90% of initial body surface area involvement) upon the final follow-up visit or at the time of ustekinumab treatment discontinuation. Concomitant systemic treatments, primarily methotrexate, were given to 59 (50%) patients. Twenty-three (19%) patients discontinued treatment, primarily for sub-optimal response or loss of response. Fifty (42%) patients required either an increase in the dose of ustekinumab to 90 mg and/or administration more frequently than every 12 weeks to achieve and maintain psoriasis clearance. PMID- 25116967 TI - A randomized, double-blinded trial evaluating the efficacy and tolerability of vectical ointment (calcitriol 3 mcg/g ointment) when compared to betamethasone diproprionate ointment (64 mg/g) in patients with nail psoriasis. AB - OBJECTIVES: To demonstrate the efficacy and safety of calcitriol ointment (3 mcg/g) compared to betamethasone diproprionate ointment in the treatment of nail psoriasis. DESIGN: Single-center, double-blind study. SETTING: One academic center. PARTICIPANTS: 10 adult male and female subjects with psoriasis of the fingernails and/or toenails. MEASUREMENTS: The primary efficacy evaluation was the absolute reduction of nail thickness (mm) of the target nail. A secondary endpoint was the improvement in the Physician Global Assessment score of disease severity. RESULTS: Patients treated with either betamethasone diproprionate ointment or calcitriol ointment demonstrated a similar reduction of nail thickness of the selected target nail. The difference between the two groups was not statistically significant (P=0.42). CONCLUSION: This small study illustrates that calcitriol ointment may be as effective as betamethasone diproprionate in the treatment of nail psoriasis, and its promise should be further investigated in a subsequent larger trial. PMID- 25116968 TI - Trends in systemic psoriasis treatment therapies from 1993 through 2010. AB - BACKGROUND: Moderate-to-severe psoriasis generally requires systemic therapy, and is often undertreated. OBJECTIVE: To determine and analyze what courses of treatment and in what frequency are being utilized to combat psoriasis in the United States. METHODS: Analysis of data from the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS) of the National Center for Health Statistics. Data were analyzed to examine the prevalence of different therapy techniques to combat psoriasis from 1993 through 2010. The trends for phototherapy, methotrexate (MTX), retinoids, cyclosporine A (CSA), systemic steroids, and biologics were all analyzed over the entire 18-year period and independently before and after the introduction of biologics in 2002. RESULTS: From 1993 to 2010, the trend for total systemic treatments has not significantly increased (P=0.5). Frequency of phototherapy treatments significantly decreased from 1993 to 2010 (P<0.001). Since the introduction of biologics in 2002, their frequency has significantly increased, becoming the most frequently used treatment from 2008-2010 (P<0.0001). LIMITATIONS: Severity of psoriasis was not recorded in the NAMCS and NHAMCS. CONCLUSIONS: The frequency of systemic treatments to treat psoriasis has not significantly increased from 1993 to 2010. Despite the introduction of biologics, it appears that little progress has been made in reducing under-treatment of moderate-to-severe psoriasis. PMID- 25116969 TI - A randomized, prospective, sham-controlled study of localized narrow-band UVB phototherapy in the treatment of plaque psoriasis. AB - IMPORTANCE: UV phototherapy remains a useful and frequently employed treatment for chronic plaque psoriasis. In those patients with plaque body surface area less than 10%, targeted treatment is the safest and most effective modality. OBJECTIVE: We aimed to evaluate the efficacy of the Levia(r) localized NB-UVB phototherapy machine in the treatment of patients with symmetrical psoriatic lesions. DESIGN: We performed a prospective, double-blinded, sham-treatment controlled study of this device beginning March 2012 through April 2014. SETTING: a comprehensive dermatology clinic in the northeastern United States. PARTICIPANTS: 21 subjects with chronic plaque psoriasis. INTERVENTIONS: Each patient had one lesion randomized to receive the Levia treatment and one lesion (the control) treated with visible light. Treatment was administered three times a week for twelve weeks. Target lesion score (TLS), a rating of 0-4 each of erythema, scaling, and thickness, was measured biweekly by a blinded assessor, and visual analogue scale of pruritus was recorded by subjects. MAIN OUTCOMES AND MEASURES: The primary outcome, formulated prior to study initiation, was the percentage of lesions achieving clear or almost clear TLS after 12 weeks of treatment. Secondary endpoints included changes in target lesion pruritus VAS, percentage improvement in TLS, and the percentage of subjects achieving 50% improvement in TLS (TLS-50). RESULTS: The primary endpoint, TLS of three or less, was not achieved (P=0.118), but the secondary endpoints of percentage improvement in TLS (P=0.043) and TLS-50 (P=0.0195) were significantly superior in treated compared to sham-treated lesions. Percentage improvement in pruritus VAS was not significant (P=0.0565). CONCLUSIONS AND RELEVANCE: This device was found to be efficacious, though not necessarily to the point of clearance, in the treatment of psoriasis over a 12-week period. TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT02107482, http://clinicaltrials.gov/show/NCT02107482 PMID- 25116970 TI - The use of self-administered subcutaneous methotrexate for the treatment of psoriasis. AB - For nearly 5 decades, methotrexate has been the backbone of moderate-to-severe psoriasis treatment. The benefits of methotrexate therapy include reliable efficacy, low cost, relative ease of administration, and its usefulness as part of combination therapy regimens, making it a drug of choice for treating psoriasis. While methotrexate can be administered orally, intravenously, or intramuscularly, the self-administered subcutaneous use of the drug is the most advantageous route. Subcutaneous methotrexate is associated with fewer adverse events and higher absorption rates, accompanied by bioavailability that is both linear and predictable throughout the range of possible doses. In addition, the subcutaneous route, when compared with oral administration, facilitates improved efficacy by promoting higher intracellular levels of long-chain methotrexate polyglutamates. Taken together, these features allow patients the highest probability of a successful therapeutic experience. Subcutaneous methotrexate should be considered a viable option for the appropriate patient with moderate-to severe psoriasis. PMID- 25116971 TI - Tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis, psoriatic arthritis, or both. AB - OBJECTIVES: To stratify MI risk reduction in those treated with a TNF inhibitor for psoriasis only, psoriatic arthritis only, or both psoriasis and psoriatic arthritis. DESIGN: Retrospective cohort study. SETTING: Between January 1, 2004 and November 30, 2010. PARTICIPANTS: At least 3 ICD9 codes for psoriasis (696.1) or psoriatic arthritis (696.0) (without antecedent MI. INTERVENTION: None MAIN OUTCOME MEASURE: Incident MI. RESULTS: When comparing to those not treated with TNF inhibitors (reference group), of those treated with TNF inhibitors: those with psoriasis only (N= 846) had a significant decrease in MI risk (hazard ratio (HR), 0.26; 95% CI, 0.12-0.56); those with psoriatic arthritis only (N= 112) had a non-significant decrease in MI risk (HR, 0.86; 95% CI, 0.28-2.70); those with both psoriasis and psoriatic arthritis (N= 715) had a non-significant decrease in MI risk (HR, 0.76; 95% CI, 0.47-1.24). CONCLUSIONS: In the TNF inhibitor cohort, those with psoriasis only have the strongest association with MI risk reduction, followed by those with psoriatic arthritis only, and then followed by those with both psoriasis and psoriatic arthritis. PMID- 25116972 TI - The basic science of natural ingredients. AB - Herbal products have steadily gained popularity as alternatives to conventional, synthetic medications and are sought after by patients for the treatment of chronic dermatologic diseases and for cosmeceutical use. The production and distribution of botanical extracts is largely unregulated and therefore extensive research into their mechanism of action, safety, physiologic stability, and optimal dosing has been overlooked. One of the major pathways through which natural supplements, particularly polyphenols, act is via inhibition of oxidative stress and its downstream mediators. Endogenous defense mechanisms are inadequate to combat oxidative stress and therefore dietary and/or topical supplementation with polyphenols are an important complementary preventative and therapeutic strategy. This review focuses on the molecular targets of common polyphenols used in topical preparations, particularly soy, green tea, oats, curcumin, and silymarin. Continued research into bioavailability and function of these agents will help translate their therapeutic potential to treat clinical disease. PMID- 25116973 TI - Targeted therapy for cutaneous oncology: a review of novel treatment options for non-melanoma skin cancer: part I. AB - The field of cutaneous oncology is exploding with innovative treatment options, specifically in the field of targeted therapy. These advances offer new hope to select patients with high risk skin cancers. Here we provide a two part series reviewing targeted therapy for non-melanoma skin cancer. We begin our discussion with basal cell carcinoma, moving beyond the first-in-class hedgehog inhibitors and highlighting promising clinical trials. PMID- 25116974 TI - Targeted therapy for cutaneous oncology: a review of novel treatment options for non-melanoma skin cancer: part II. AB - The field of cutaneous oncology is exploding with innovative treatment options, specifically in the field of targeted therapy. These advances offer new hope to select patients with high risk skin cancers. In part two of our series on targeted therapy for skin cancer, we focus our attention on squamous cell carcinoma. We begin with the epidermal growth factor receptor inhibitors and branch out into newer areas of active research. PMID- 25116975 TI - The science behind common over-the-counter remedies used in dermatology. AB - There are many over-the-counter products used to treat dermatological conditions. Patients are inundated with information about these products. Dermatologists often encounter questions about the usefulness of over-the-counter products as anecdotal data about such products is often adapted as common practice in the medical field. Modern dermatology training does not include pharmacological education on many of the over-the-counter products commonly used by patients. In this current age when patients have increasing interest in using "natural" remedies, it is important that dermatologists can provide guidance to patients regarding some of the most common products that they may encounter. This article is designed to provide introductory information on the common uses for several over-the-counter products as well as to display any evidence in support of these products for dermatological diseases. PMID- 25116976 TI - How suture technique affects the cosmetic outcome of cutaneous repairs. AB - INTRODUCTION: Skin defects can be repaired via primary closure, secondary intention healing, local and distant flaps, skin grafts or application of natural and synthetic skin substitutes. When possible, primary linear repair is favored due to simplicity, minimal morbidity and rapid healing. A number of suture techniques are available to the surgeon for primary closure, the selection of which depends on defect size, anatomic location, wound eversion, and tension.
OBJECTIVE: To review suture techniques and how they influence scar cosmesis.
METHODS: PubMed was searched using the following key words: cosme* in combination with cutaneous suture, simple interrupted, simple running, running locked, vertical mattress, horizontal mattress, buried, subcuticular, running vertical mattress, running horizontal mattress, buried vertical mattress, butterfly suture, or pulley suture. Information on study type, number of patients, age, gender, defect type, anatomic location, suture technique, scar length, follow up, and outcomes measured were tabulated.
RESULTS: Twenty-four articles - 17 prospective randomized controlled trials including 1,473 subjects and 1,608 repairs and seven case series including 465 subjects and repairs - were reviewed. Fifteen articles - 12 randomized controlled trials and three case series - demonstrated that aesthetic outcome was influenced by suture technique, the majority of which showed subcuticular closure to be superior to simple interrupted or simple running sutures. No difference in aesthetic outcome was observed in nine studies, which included 370 repairs.
DISCUSSION: Review of the literature supports the use of subcuticular closure over simple interrupted or simple running sutures on the trunk and extremities for improved aesthetic outcome. PMID- 25116977 TI - Safety and effectiveness of ustekinumab for treatment of moderate to severe psoriasis: a prospective study in a clinical setting. AB - BACKGROUND: There are few studies analyzing the behavior of ustekinumab in the complex management of psoriasis within diary clinical practice setting. OBJECTIVE: To assess the utility of ustekinumab in a psoriasis unit. METHODS: Analysis of the prospective data gathered during the follow-up of 30 consecutive psoriasis patients treated with ustekinumab at a single referral centre. Three effectiveness endpoints were defined 12 weeks, 28 and "long-term treatment". The main outcome measure was improvement from baseline PASI at week 28 and at a point of adjustment of prolonged treatment signed as "long-term treatment". RESULTS: Overall 82.1% and 42.8% patients achieved respectively PASI75 and PASI90 response rates at week 28. Long-term treatment maintained efficacy outcomes 81.5% and 40.7% PASI75 and PASI90, respectively were observed. At week 28, patients naive to TNFalpha- blockers agents and patients with a baseline PASI >10 had better PASI75 and PASI90 response rates than previously treated patients. CONCLUSIONS: In clinical practice, the efficacy and patient adherence to ustekinumab are excellent and even better to the data obtained in clinical trials. Clinical indicators of psoriasis severity: previous treatments with tumor necrosis factor alpha blockers agents and active treatment beside small increases in PASI determine a delayed maximal response. PMID- 25116978 TI - Disseminated botryomycosis: a rare presentation. AB - Botryomycosis is a rare chronic bacterial infection of the skin or viscera that resembles a deep fungal infection. Botryomycosis has two distinct patterns of infection, visceral and cutaneous, the latter being the most common. Cutaneous botryomycosis typically appears as a solitary plaque with superficial pustules. Histologically, bacterial colonies are arranged in a distinctive "bunch of grapes" pattern with surrounding eosinophilia, known as the Splendore-Hoeppli phenomenon. Here we report a case of an 83-year-old female with disseminated botryomycosis. PMID- 25116979 TI - Flagellate erythema secondary to bleomycin: a new case report and review of the literature. AB - Bleomycin is an antibiotic with antineoplastic properties. It is used in the treatment of different tumors in oncology. The mucocutaneous side effects of this drug include ulcers, scaly erythematous and bullous lesions, sclerosis, stomatitis, and pigmentary alterations. Flagellate erythema is a characteristic hyperpigmentation of bleomycin. We report a case of flagellate erythema following the administration of bleomycin in a 34-year-old woman with ovarian teratoma. She developed linear lesions two weeks after the first injection of bleomycin. Flagellate erythema is a specific reaction to bleomycin therapy, which occurs in susceptible individuals independently of dose, route of administration, and type of malignant disease treated. PMID- 25116980 TI - Pseudoporphyria: discussion of etiologic agents. AB - Pseudoporphyria describes a photodistributed bullous disorder with negative urinary, fecal, and serum porphyrin studies. Although pseudoporphyria is thought to be extremely rare (less than 100 reported cases4-5), we propose that this entity is underreported. One author (KB) has seen four cases of pseudoporphyria in the past four years. We describe a patient with nonpruritic, nonpainful bulla on the dorsum of his hands. Biopsy revealed a split at the dermal-epidermal junction; laboratory tests and urinary porphyrin evaluation were negative. PMID- 25116981 TI - Why do we need another moisturizer for our acne patients? PMID- 25116982 TI - The importance of photoprotection and moisturization in treating acne vulgaris. AB - Skin care products are recognized by dermatologists as critical adjunctive therapeutic modalities for patients suffering from acne vulgaris (AV). Prescribing an acne medication without reviewing a patient's skin care regimen can lead to poor compliance, intolerable side effects, and resulting patient and physician frustration. Striking that delicate balance between maintaining the skin barrier while controlling oil and shine has always been a challenge when treating this chronic inflammatory condition, and it necessitates a unique set of ingredients and formulation. Cetaphil(r) DermaControlTM Moisturizer SPF 30 (Galderma Laboratories, L.P., Fort Worth, Texas) is a new generation of skin care specifically designed for acne-prone skin and acne-affected skin. Both Cetaphil(r) DermaControlTM Foam Wash and Cetaphil DermaControl Moisturizer SPF 30 incorporate pharmacologically tested, state-of-the-art ingredients and technologies that studies have shown impart substantial benefits to AV patients. PMID- 25116985 TI - We the living. PMID- 25116983 TI - Characteristics, treatment practices, and in-hospital outcomes of older adults hospitalized with acute myocardial infarction. AB - OBJECTIVES: To examine overall and decade-long trends (1999-2009), characteristics, treatment practices, and hospital outcomes in individuals aged 65 and older hospitalized for acute myocardial infarction (AMI) and to describe how these factors varied in the youngest, middle, and oldest-old individuals. DESIGN: Retrospective cohort study. SETTING: Population-based Worcester Heart Attack Study. MEASUREMENTS: Analyses were conducted to examine the sociodemographic and clinical characteristics, cardiac treatments, and hospital outcomes of older adults in three age strata (65-74, 75-84, >=85). PARTICIPANTS: The study sample consisted of 3,851 individuals aged 65 and older hospitalized with AMI every other year between 1999 and 2009; 32% were aged 65 to 74, 43% aged 75 to 84, and 25% aged 85 and older. RESULTS: Advancing age was inversely associated with receipt of evidence-based cardiac therapies. After multivariable adjustment, the odds of dying during hospitalization was 1.46 times as high in participants aged 75 to 84 and 1.78 times as high in those aged 85 and older as in those aged 65 to 74. The oldest-old participants had approximately 25% lower odds of a prolonged hospital stay (>3 days) than those aged 65 to 74. Decade-long trends in the principal study outcomes were also examined. Although the oldest old participants hospitalized for AMI were at the greatest risk of dying, persistent age-related differences were observed in hospital treatment practices. Similar results were observed after excluding participants with a do-not resuscitate order in their medical records. CONCLUSION: Although there are persistent disparities in the care and outcomes of older adults hospitalized with AMI, additional studies are needed to delineate the extent to which less aggressive care reflects individual preferences and appropriate implementation of palliative care approaches. PMID- 25116986 TI - Movement velocity is a sensitive risk factor of falls in high-functioning older adults. PMID- 25116984 TI - Functional benefits of tai chi training in senior housing facilities. AB - OBJECTIVES: To determine the effects of tai chi training on functional performance and walking with and without the addition of the performance of a cognitive task, in older adults living in supportive housing facilities. DESIGN: Secondary data analysis comparing a single-blind, randomized controlled trial of tai chi training with an attention-matched educational control intervention with crossover to tai chi. SETTING: Two supportive housing facilities. PARTICIPANTS: Sixty-six men and women living in supportive housing facilities entered the study, and 57 aged 87+/-7 completed all study procedures. INTERVENTION: Interventions consisted of two 1-hour-long instructor-led group sessions per week for 12 weeks. Tai chi training consisted of movements based upon the Yang-style short form. Educational sessions consisted of lectures and discussions of age related health topics. MEASUREMENTS: Subjects were tested for physical function (Short Physical Performance Battery, SPPB), balance (Berg Balance Scale, BBS), mobility (timed up-and-go, TUG), and walking speed under normal and cognitive dual-task conditions. RESULTS: The tai chi group exhibited greater improvement in SPPB scores (baseline 8.1+/-2.9, follow-up 9.0+/-2.6) than controls (baseline 8.2+/-2.6, follow-up 8.2+/-2.6) (P=.005). Tai chi also increased normal and dual task walking speed (P<.001) yet did not affect BBS (P=.02) or TUG (P=.02) after accounting for multiple comparisons. The dual-task cost (percentage change) to walking speed was unaffected. After the crossover tai chi intervention, the control group improved performance in the SPPB, BBS, and TUG, and increased walking speed under normal and dual-task conditions (P=.008). CONCLUSION: Tai chi training may be a safe and effective therapy to help improve physical function and dual-task walking in very old adults living in supportive housing facilities. PMID- 25116987 TI - (Unsuccessful) binary modeling of successful aging in the oldest-old adults: a call for continuum-based measures. PMID- 25116989 TI - Hepatitis B and hepatitis C associated with risk of gallstone disease in elderly adults. PMID- 25116988 TI - Longitudinal neuropsychological performance of cognitive SuperAgers. PMID- 25116990 TI - Falls prediction in acute care units: preliminary results from a prospective cohort study. PMID- 25116991 TI - Metabolic syndrome, executive dysfunction, and late-onset depression: just a matter of white matter? PMID- 25116992 TI - Rapidly progressive ataxia during rehabilitation and a difficult road to diagnosis. PMID- 25116993 TI - A rare entity with coffee-ground vomit in elderly adults: black esophagus. PMID- 25116994 TI - Unexpected recovery of moderate cognitive impairment on treatment with oral methylcobalamin. PMID- 25116995 TI - When the inevitable question is asked. PMID- 25116996 TI - Charlson comorbidity index in acutely hospitalized elderly adults. PMID- 25116997 TI - Response letter to Martinez-Velilla and Zekry. PMID- 25116999 TI - Response to David Nace and Paul Drinka. PMID- 25116998 TI - Cranberry capsules reducing the incidence of what? PMID- 25117000 TI - Reviewing the safety of loratadine for elderly adults: a potential shortcoming of the 2012 Beers criteria. PMID- 25117001 TI - Response to Marcio Galvao Oliveira et al. PMID- 25117003 TI - Flavonoids with antimicrobial activity from the stem bark of Commiphora pedunculata (Kotschy & Peyr.) Engl. AB - The first reported investigation into the phytochemical constituents of Commiphora pedunculata led to the isolation of two flavonoids: kaempferol and dihydrokaempferol from the ethyl acetate-soluble fraction of the methanol extract of the stem bark of the plant. The structures of these compounds were characterised by comparing their spectral data including 1D and 2D NMR with those reported in the literature. The two compounds were active against 6 out of 10 tested microorganisms including two resistant strains [methiciline-resistant Staphylococcus aureus and vancomycin-resistant entrococci (VRE)], Candida albicans and Escherichia coli. The zones of inhibition ranged between 24 and 30 mm for both compounds against the microorganisms. The MIC value was as low as 6.25 MUg/mL against VRE and Staphylococcus aureus. This is the first report of the isolation of these compounds from the plant. PMID- 25117002 TI - Probiotic properties of lactic acid bacteria isolated from water-buffalo mozzarella cheese. AB - This study evaluated the probiotic properties (stability at different pH values and bile salt concentration, auto-aggregation and co-aggregation, survival in the presence of antibiotics and commercial drugs, study of beta-galactosidase production, evaluation of the presence of genes encoding MapA and Mub adhesion proteins and EF-Tu elongation factor, and the presence of genes encoding virulence factor) of four LAB strains (Lactobacillus casei SJRP35, Leuconostoc citreum SJRP44, Lactobacillus delbrueckii subsp. bulgaricus SJRP57 and Leuconostoc mesenteroides subsp. mesenteroides SJRP58) which produced antimicrobial substances (antimicrobial peptides). The strains survived the simulated GIT modeled in MRS broth, whole and skim milk. In addition, auto aggregation and the cell surface hydrophobicity of all strains were high, and various degrees of co-aggregation were observed with indicator strains. All strains presented low resistance to several antibiotics and survived in the presence of commercial drugs. Only the strain SJRP44 did not produce the beta galactosidase enzyme. Moreover, the strain SJRP57 did not show the presence of any genes encoding virulence factors; however, the strain SJRP35 presented vancomycin resistance and adhesion of collagen genes, the strain SJRP44 harbored the ornithine decarboxylase gene and the strain SJRP58 generated positive results for aggregation substance and histidine decarboxylase genes. In conclusion, the strain SJRP57 was considered the best candidate as probiotic cultures for further in vivo studies and functional food products development. PMID- 25117004 TI - The effects of sleep deprivation on emotional empathy. AB - Previous studies have shown that sleep loss has a detrimental effect on the ability of the individuals to process emotional information. In this study, we tested the hypothesis that this negative effect extends to the ability of experiencing emotions while observing other individuals, i.e. emotional empathy. To test this hypothesis, we assessed emotional empathy in 37 healthy volunteers who were assigned randomly to one of three experimental groups: one group was tested before and after a night of total sleep deprivation (sleep deprivation group), a second group was tested before and after a usual night of sleep spent at home (sleep group) and the third group was tested twice during the same day (day group). Emotional empathy was assessed by using two parallel versions of a computerized test measuring direct (i.e. explicit evaluation of empathic concern) and indirect (i.e. the observer's reported physiological arousal) emotional empathy. The results revealed that the post measurements of both direct and indirect emotional empathy of participants in the sleep deprivation group were significantly lower than those of the sleep and day groups; post measurement scores of participants in the day and sleep groups did not differ significantly for either direct or indirect emotional empathy. These data are consistent with previous studies showing the negative effect of sleep deprivation on the processing of emotional information, and extend these effects to emotional empathy. The findings reported in our study are relevant to healthy individuals with poor sleep habits, as well as clinical populations suffering from sleep disturbances. PMID- 25117005 TI - Focal adhesion signaling and therapy resistance in cancer. AB - Interlocking gene mutations, epigenetic alterations and microenvironmental features perpetuate tumor development, growth, infiltration and spread. Consequently, intrinsic and acquired therapy resistance arises and presents one of the major goals to solve in oncologic research today. Among the myriad of microenvironmental factors impacting on cancer cell resistance, cell adhesion to the extracellular matrix (ECM) has recently been identified as key determinant. Despite the differentiation between cell adhesion-mediated drug resistance (CAMDR) and cell adhesion-mediated radioresistance (CAMRR), the underlying mechanisms share great overlap in integrin and focal adhesion hub signaling and differ further downstream in the complexity of signaling networks between tumor entities. Intriguingly, cell adhesion to ECM is per se also essential for cancer cells similar to their normal counterparts. However, based on the overexpression of focal adhesion hub signaling receptors and proteins and a distinct addiction to particular integrin receptors, targeting of focal adhesion proteins has been shown to potently sensitize cancer cells to different treatment regimes including radiotherapy, chemotherapy and novel molecular therapeutics. In this review, we will give insight into the role of integrins in carcinogenesis, tumor progression and metastasis. Additionally, literature and data about the function of focal adhesion molecules including integrins, integrin-associated proteins and growth factor receptors in tumor cell resistance to radio- and chemotherapy will be elucidated and discussed. PMID- 25117006 TI - Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: from biology to clinical use. AB - The tumor microenvironment includes a complicated network of physiological gradients contributing to plasticity of tumor cells and heterogeneity of tumor tissue. Hypoxia is a key component generating intratumoral oxygen gradients, which affect the cellular expression program and lead to therapy resistance and increased metastatic propensity of weakly oxygenated cell subpopulations. One of the adaptive responses of tumor cells to hypoxia involves the increased expression and functional activation of carbonic anhydrase IX (CA IX), a cancer related cell surface enzyme catalyzing the reversible conversion of carbon dioxide to bicarbonate ion and proton. Via its catalytic activity, CA IX participates in regulation of intracellular and extracellular pH perturbations that result from hypoxia-induced changes in cellular metabolism producing excess of acid. Through the ability to regulate pH, CA IX also facilitates cell migration and invasion. In addition, CA IX has non-catalytic function in cell adhesion and spreading. Thus, CA IX endows tumor cells with survival advantages in hypoxia/acidosis and confers an increased ability to migrate, invade and metastasize. Accordingly, CA IX is expressed in a broad range of tumors, where it is associated with prognosis and therapy outcome. Its expression pattern and functional implications in tumor biology make CA IX a promising therapeutic target, which can be hit either by immunotherapy with monoclonal antibodies or with compounds inhibiting its enzyme activity. The first strategy has already reached the clinical trials, whereas the second one is still in preclinical testing. Both strategies indicate that CA IX can become a clinically useful anticancer target, but urge further efforts toward better selection of patients for immunotherapy and deeper understanding of tumor types, clinical situations and synthetic lethality interactions with other treatment approaches. PMID- 25117007 TI - Regulatory role of glycans in the control of hypoxia-driven angiogenesis and sensitivity to anti-angiogenic treatment. AB - Abnormal glycosylation is a typical hallmark of the transition from healthy to neoplastic tissues. Although the importance of glycans and glycan-binding proteins in cancer-related processes such as tumor cell adhesion, migration, metastasis and immune escape has been largely appreciated, our awareness of the impact of lectin-glycan recognition in tumor vascularization is relatively new. Regulated glycosylation can influence vascular biology by controlling trafficking, endocytosis and signaling of endothelial cell (EC) receptors including vascular endothelial growth factor receptors, platelet EC adhesion molecule, Notch and integrins. In addition, glycans may control angiogenesis by regulating migration of endothelial tip cells and influencing EC survival and vascular permeability. Recent evidence indicated that changes in the EC surface glycome may also serve "on-and-off" switches that control galectin binding to signaling receptors by displaying or masking-specific glycan epitopes. These glycosylation-dependent lectin-receptor interactions can link tumor hypoxia to EC signaling and control tumor sensitivity to anti-angiogenic treatment. PMID- 25117008 TI - In vitro biological characterization of IFN-beta-1a major glycoforms. AB - Recombinant human interferon beta-1a (IFN-beta-1a) is extensively used as the first-line treatment of relapsing forms of multiple sclerosis. Its glycosylation is recognized as having a complex impact on a wide range of molecule characteristics and functions. The present study reports the enrichment of IFN beta-1a glycoforms and their physicochemical and biological characterization by means of electrospray ionization-mass spectrometry, sialic acid content, thermal denaturation and various in vitro bioassays (antiproliferative, antiviral, immunomodulatory and reporter gene assay). The glycoforms were fractionated by means of cation-exchange chromatography using recombinant IFN-beta-1a derived from Chinese Hamster Ovary cell culture as starting material. The obtained fractions contained bi- and higher-antennarity glycans as described in the European Pharmacopoeia monograph (Nr. 1639E, Interferon beta 1a concentrated solution). The in vitro bioassay responses revealed a correlation mainly with the glycan antennarity. It is therefore suggested that all glycoforms have biological activity and play a role in modulating the overall IFN-beta biological activity with higher-antennarity glycoforms being able to better sustain IFN-beta-1a bioactivity over time. These data indicate the role of IFN-beta-1a glycosylation in vivo and shed new light on the role of the glycosylation heterogeneity, in particular with regard to antennarity, on biological properties of glycoproteins. PMID- 25117009 TI - Assessment of cultivation factors that affect biomass and geraniol production in transgenic tobacco cell suspension cultures. AB - A large-scale statistical experimental design was used to determine essential cultivation parameters that affect biomass accumulation and geraniol production in transgenic tobacco (Nicotiana tabacum cv. Samsun NN) cell suspension cultures. The carbohydrate source played a major role in determining the geraniol yield and factors such as filling volume, inoculum size and light were less important. Sucrose, filling volume and inoculum size had a positive effect on geraniol yield by boosting growth of plant cell cultures whereas illumination of the cultures stimulated the geraniol biosynthesis. We also found that the carbohydrates sucrose and mannitol showed polarizing effects on biomass and geraniol accumulation. Factors such as shaking frequency, the presence of conditioned medium and solubilizers had minor influence on both plant cell growth and geraniol content. When cells were cultivated under the screened conditions for all the investigated factors, the cultures produced ~ 5.2 mg/l geraniol after 12 days of cultivation in shaking flasks which is comparable to the yield obtained in microbial expression systems. Our data suggest that industrial experimental designs based on orthogonal arrays are suitable for the selection of initial cultivation parameters prior to the essential medium optimization steps. Such designs are particularly beneficial in the early optimization steps when many factors must be screened, increasing the statistical power of the experiments without increasing the demand on time and resources. PMID- 25117012 TI - Quality and safety in healthcare - a challenge accepted. PMID- 25117010 TI - Hermansky-Pudlak syndrome. Overview of clinical and molecular features and case report of a new HPS-1 variant. AB - Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder affecting lysosome-related organelles (LRO), including dense platelet granules. HPS causes oculocutaneous hypopigmentation, bleeding diathesis and granulomatous colitis or pulmonary fibrosis. To date, there is no curative treatment and the clinical management depends on the severity of symptoms. A prompt diagnosis of HPS patients could improve their quality of life and clinical management. However, the absence of a specific platelet function test, the wide molecular heterogeneity, and the lack of phenotype-genotype correlations hamper the rapid diagnosis. Nine subtypes of HPS have been identified as a result of mutations in nine genes that codify for proteins involved in formation and shuttle of the LRO. The molecular characterization of patients and knowledge derived from animal models of HPS contribute to the understanding of biogenesis and function of the LRO. This paper describes a patient with a novel homozygous nonsense mutation causing HPS and provides a review of the literature focusing on recent advances in the molecular characterization and physiopathology of HPS. PMID- 25117013 TI - Retrospective studies provide valuable information. PMID- 25117014 TI - 'In somno securitas - semper vigilans'? PMID- 25117015 TI - Continuous posterior TAP analgesia after laparoscopic colorectal surgery. PMID- 25117016 TI - TAP block terminology. PMID- 25117017 TI - Subcostal TAP block and postoperative respiratory function after abdominal surgery. PMID- 25117018 TI - Anaesthesia-related outcome after hip fracture. PMID- 25117019 TI - A reply. PMID- 25117020 TI - Cognitive aid for malignant hyperpyrexia. PMID- 25117021 TI - SonixGPS - the role of operator experience. PMID- 25117022 TI - A reply. PMID- 25117023 TI - Driving advice after isoflurane anaesthesia. PMID- 25117024 TI - The effect of general anaesthesia on memory in children. PMID- 25117025 TI - Problem with Portex 'loss of resistance' syringes. PMID- 25117026 TI - Main trunk crossover stenting in a patient with left internal thoracic artery- protected single coronary artery. AB - A 74-year-old man with single coronary artery and history of previous coronary artery bypass graft (CABG) was admitted to our hospital with worsening angina. Because of high risk of redo-CABG, we performed transradial percutaneous coronary intervention against the just proximal left anterior descending coronary artery (LAD) stenosis coexisting with short main trunk, anomalous right coronary artery deriving from the mid LAD and patent left internal thoracic artery-distal LAD graft. Under the guidance of IVUS, we successfully implanted an everolimus eluting stent from the main trunk ostium to the proximal LAD without complications. PMID- 25117027 TI - Toxicity of naturally occurring Bio-fly and chitosan compounds to control the Mediterranean fruit fly Ceratitis capitata (Wiedemann). AB - The efficacy of five compounds of a biopolymer chitosan and Bio-fly (Beauveria bassiana fungus) as biopesticide was evaluated on Ceratitis capitata under laboratory conditions. The inhibitory effects on acetylcholinesterase (AChE) and adenosinetriphosphatase (ATPase) as biochemical indicators were also determined in vivo. The results indicated that B. bassiana based Bio-fly exhibited significant toxicity against C. capitata (LC50 = 3008 and 3126 mg/L after 48 h in females and males, respectively) followed by the derivatives of chitosan, N-(4 propylbenzyl)chitosan and N-(2-nitrobenzyl)chitosan. Bio-fly displayed remarkable inhibition of AChE activity (IC50 = 2220 mg/L) while N-(2-chloro,6 flourobenzyl)chitosan, N-(4-propylbenzyl)chitosan and N-(3,4 methylenedioxybenzyl) chitosan had no significant difference in inhibitory action. In adult males, N-(2-nitrobenzyl)chitosan exhibited the highest inhibitory action (IC50 = 6569 mg/L). In addition, the toxic effects of the tested compounds on the activity of ATPase indicated that highly significant inhibition was found with N-(4-propylbenzyl)chitosan with an IC50 of 8194 and 8035 mg/L, in females and males, respectively. PMID- 25117028 TI - The complex, non-monotonic thermal response of the volumetric space of simple liquids. AB - In this paper, an intricate effect of the isothermal compression of simple liquids on their volumetric response is reported for alpha,omega-halogenoalkanes as examples. We apply an accurate experimental technique, scanning transitiometry, to directly measure isobaric thermal volume expansivities alphap of the liquids in a wide density range. To thoroughly analyze the observed intersection of the experimental isothermal pressure dependences of alphap, we develop a class of equations of state derived in the density scaling regime for molecular dynamics, finding successful temperature parameterizations of an isothermal equation of state (EOS) intrinsically adapted to describe volumetric data in an extremely wide density range. The EOS based analyses of the scanning transitiometry data as a function of temperature T and pressure p undoubtedly show that the previously considered crossing point of the isothermal dependences alphap(p) is in general represented by a non-linear and non-monotonic curve in the (T-p) phase diagram. PMID- 25117030 TI - [Focal autoimmune pancreatitis versus pancreatic cancer: value of steroid treatment in the diagnosis]. AB - BACKGROUND: The differential diagnosis of pancreatic cancer and focal forms of autoimmune pancreatitis is complicated since serological tests, IgG4 and CA 19-9 have a low sensibility and specificity. CT scan and magnetic resonance imaging provide clear differentiation in the majority, but not in all cases. Endosonography is the most precise diagnostic procedure and allows to obtain samples for cytology or even histological studies. AIM: To report the experience with 18 cases of focal autoimmune pancreatitis and three cases of pancreatic cancer. MATERIAL AND METHODS: Review of medical records of 18 patients with focal autoimmune pancreatitis and 3 cases of pancreatic cancer. RESULTS: The eighteen patients with focal autoimmune pancreatitis were treated with prednisone 0.5 mg/kg/day obtaining a complete clinical and morphological recovery in all. However, 3 had a relapse and one was operated. During follow up, none has developed a pancreatic cancer. The 3 patients with pancreatic cancer did not respond to steroidal treatment. CONCLUSIONS: The quick and dramatic response to steroids of autoimmune pancreatitis, may be useful and is recommended for the differential diagnosis with pancreatic cancer. PMID- 25117029 TI - Alcohol expectancies in childhood: change with the onset of drinking and ability to predict adolescent drunkenness and binge drinking. AB - AIMS: We examined the relationship between alcohol expectancies in childhood and onset of drinking, binge drinking and drunkenness in adolescence and the influence of drinking onset on expectancy development. DESIGN: A prospective, longitudinal study of children assessed for alcohol expectancies and drinking at four time-points between ages 6 and 17 years. SETTING: Community study of families at high risk for alcoholism conducted in a four-county area in the Midwestern United States. PARTICIPANTS: The study involved 614 children; 460 were children of alcoholics and 70% were male. MEASUREMENTS: Expectancies about alcohol effects were measured using the Beverage Opinion Questionnaire and child's drinking by the Drinking and Drug History-Youth Form. FINDINGS: Partial factor invariance was found for expectancy factors from ages 6 to 17 years. Survival analysis showed that social/relaxation expectancies in childhood predicted time to onset of binge drinking and first time drunk (Wald chi(2) , 1 d.f. = 3.8, P = 0.05 and 5.0, P < 0.05, respectively). The reciprocal effect was also present; when adolescents began drinking, there was an increase in social/relaxation expectancy and a concomitant increase in slope of the expectancy changes lasting throughout adolescence. CONCLUSIONS: A reciprocal relationship exists between childhood alcohol expectancies and the development of alcohol involvement. Higher expectancies for positive effects predict earlier onset of problem drinking. Onset of use, in turn, predicts an increase in rate of development of positive expectancies. PMID- 25117031 TI - [Factors associated with health promoting behaviors among Chilean adolescents]. AB - BACKGROUND: Health-promoting behaviors are important to prevent diseases and prolong life in the population. People develop these behaviors throughout life. However, better benefits for health are obtained with an early development. AIM: To determine the prevalence of health-promoting behaviors among early adolescents and its associated factors. MATERIAL AND METHODS: Cross-sectional survey performed in 1,465 students of high, medium and low socio-economic status, attending fifth to eighth grades of schools located in a small Chilean city. Participants answered a questionnaire that gathered information about frequency of health-promoting behaviors such as health responsibility and nutrition, physical exercise and stress management, life appreciation, social support and different personal, school and familial factors. RESULTS: A higher frequency of health-promoting behaviors was associated with better academic achievement, better school commitment, and higher perception of school membership. It also was associated with a better perception of health status and a higher conformity with physical appearance. CONCLUSIONS: Health promoting behaviors in these children are related to a better academic achievement and a higher integration with school environment. PMID- 25117033 TI - [Effects of education and strength training on functional tests among older people with osteoarthritis]. AB - BACKGROUND: Hip and knee osteoarthritis are important causes of pain and disability among older people. Education and strength training can alleviate symptoms and avoid functional deterioration. AIM: To assess muscle strength, fall risk and quality of life of older people with osteoarthritis and the effects of physiotherapy education and strength training on these variables. MATERIAL AND METHODS: Thirty participants aged 78 +/- 5 years (63% women) were randomly assigned to receive physiotherapy (Controls), physiotherapy plus education (Group 1) and physiotherapy plus strength training (group 2). At baseline and after 16 weeks of intervention, patients were evaluated with the Senior Fitness Test, Timed Up and Go and Quality of Life score short form (SF-36). RESULTS: During the intervention period, Senior Fitness Test and Timed Up and Go scores improved in all groups and SF-36 did not change. The improvement in Senior Fitness Test and Timed Up and Go was more marked in Groups 1 and 2 than in the control group. CONCLUSIONS: Education and strength training improve functional tests among older people with osteoarthritis. PMID- 25117032 TI - [Survival of patients with metastatic breast cancer according to pathological types of tumors]. AB - BACKGROUND: The prognosis of breast cancer (BC) is in part determined by the stage at diagnosis and its pathological characteristics. AIM: To evaluate the association between survival of women with metastatic breast cancer and pathological features of the tumor. PATIENTS AND METHODS: We obtained clinical and pathological data from patients diagnosed with a metastatic BC between 1999 and 2013. The expression of estrogen (ER) and progesterone (PR) receptors and human epidermal growth factor receptor 2 (HER2) was determined by immunohistochemistry. Clinicopathological subtypes were defined as: Luminal A: ER or PR positive, HER2 negative, histological grade (HG) 1 or 2; Luminal B: ER or PR positive, HER2 negative or positive or HG 3; triple negative (TN): ER, PR and HER2 negative, independent of the HG, positive HER2: ER, PR negative and HER2 positive, independent of HG. We analyzed survival based on these subtypes. RESULTS: We identified 54 patients aged 24 to 85 years, with metastatic BC at diagnosis. Seventy five percent had luminal tumors; 19.6% HER2 positive and 7.8% were TN. In 61% of evaluable tumors, HG was classified as 3. The frequency of HER2 positive and high HG tumors was greater in these patients with metastatic BC than in a non-metastatic local BC cohort. Survival was higher among patients with Luminal tumors than in women with non-Luminal cancer (56.4 and 11.4 months, respectively, p = 0.04). CONCLUSIONS: Patients with metastatic BC at diagnosis often had HER2 positive tumors and high HG. As in other studies, ER positive tumors had a better survival. PMID- 25117034 TI - [Exposure to occupational biological risks: experience of a toxicology information center]. AB - BACKGROUND: Exposure to Biological Agents during work is an emergent type of occupational risk. AIM: To characterize occupational biological risk exposure among Chilean workers which have been registered by the Toxicology Information Center, between January 2006 and December 2009. MATERIAL AND METHODS: All incoming calls reporting exposure to biological agents during the studied period were analyzed. The information obtained from the caller was registered using the Communication Record Instrument of the WHO International Programme on Chemical Safety (IPCS INTOX). RESULTS: In the studied period, 77 calls were received. The mean age of exposed patients was 35 +/- 15 years and 57% of them were females. The most common involved agents were vaccines for veterinary use (42%) followed by Loxosceles laeta bites in 16%. The main routes of exposure were injections, cuts and needle stick injuries in 39% and stings and bites in 38%. The highest exposure rates were observed in Southern Chile due to self-inoculation of veterinary vaccines used in the salmon industry (22.7/100.000 actual workers). Fifty-eight percent of calls were from health care workers, and 51% of them were from health care facilities. Sixty percent of exposures occurred during summer and spring. There was a fourfold higher risk of calls involving women exposed to bites or stings (odds ratio (OR) 4.5 (CI95 1.5-13.9, p < 0.01). Men had a fourfold higher risk of being exposed to vaccines or medications for veterinary use (OR 4.2, CI95 1.4-12.6 p < 0.01). CONCLUSIONS: Most calls involving an exposure to a biological agent were caused by self-inoculation of veterinary medications. PMID- 25117035 TI - [Association between psychological stress and metabolic control in patients with type 1 diabetes mellitus]. AB - BACKGROUND: An association between psychological stress and metabolic control can occur in patients with diabetes. AIM: To determine the longitudinal association between different psychological stress domains (emotional burden, physician related distress, regimen-related distress, diabetes-related interpersonal distress) and metabolic control of adolescents with Type 1 diabetes. MATERIAL AND METHODS: An intentional sample of 20 Type 1 diabetic adolescents aged 15 +/- 4 years was followed-up for one year. Three HbA1c determinations were performed and a stress self-report was obtained with the Polonsky' Diabetes Distress Scale. RESULTS: Several analyses were conducted using growth curve modeling. The first model included the HbA1c measures, the time term (coded as 0, 1, 2) and several covariates (age, years living with type 1 diabetes mellitus, sex, and physical activity). An overall negative linear trend was found for HbA1c. Subsequent models added the stress domains finding that high levels of emotional burden and regimen related-distress were associated with higher HbA1c levels across all exams. A marginal association was found between diabetes-related interpersonal distress and HbA1c. CONCLUSIONS: Stress levels in type 1 diabetic adolescents deserve attention. Different psychological stress factors predicting metabolic control trajectories in type 1 diabetic adolescents were found. PMID- 25117036 TI - [Eight weeks of combined high intensity intermittent exercise normalized altered metabolic parameters in women]. AB - BACKGROUND: Short term physical training programs may improve insulin resistance and hyperglycemia. AIM: To assess the effects of eight weeks of combined exercise program on serum lipids and glycemic level in women with hyperglycemia and hypercholesterolemia. PATIENTS AND METHODS: Ten healthy women, nine women with hyperglycemia, ten with hypercholesterolemia and nine with hyperglycemia/hypercholesterolemia were studied. Participants were subjected to eight weeks into a program of combined physical exercise (high intensity interval + resistance training). RESULTS: Fasting glycemia decreased by 12 and 14% in hyperglycemic and hyperglycemic/hypercholesterolemic participants, respectively. Serum insulin decreased in all groups in a range from 27 to 37%. HOMA IR for insulin resistance decreased similarly. A significant decrease in TC and TG was observed only in those altered baseline subjects. CONCLUSIONS: Eight weeks of combined physical exercise had a favorable effect on insulin resistance in this group of women. PMID- 25117037 TI - [Cardiovascular risk factors among males in 1989 and 2011-12 in a southern Chilean city]. AB - BACKGROUND: A successful cardiovascular prevention program should induce a reduction of risk factors along time. AIM: To assess changes in cardiovascular risk factors among males aged between 35 and 65 years living in Southern Chile. MATERIAL AND METHODS: The results of two cross sectional household surveys, with a probability sampling stratified by socioeconomic status, were analyzed. Two hundred males were evaluated in 1989 and 800 in 2011-12, paired by age for selection. RESULTS: In the second survey, a mean weight increase of 4.5 kg was recorded. Body mass index increased from 27.1 to 28.6 kg/m(2) (p < 0.01), especially in men younger than 45 years old. No changes in smoking prevalence were observed. The prevalence of hypertension and hypertensive patients in treatment increased from 32.7 to 38.1% and from 17 to 33%, respectively. The number of treated hypertensive patients with a well-controlled blood pressure did not change significantly. In 1989 and 2011-12, mean total cholesterol values were 192 and 201 mg/dl respectively (p < 0.01). The figures for mean non-HDL cholesterol were 152 and 160 mg/dl (p = 0.03). The frequency of people with total cholesterol over 240 mg/dl or using statins increased from 15 to 25% (p < 0.01). The estimated 10 years risk of myocardial infarction and coronary death using Framingham tables was 9,0 in both periods (p = 0.95). CONCLUSIONS: In a 22 years period an increase in the prevalence of obesity and elevated total cholesterol was observed. There was a higher proportion of individuals treated for hypertension and dyslipidemia, but without reduction in the estimated cardiovascular risk. PMID- 25117038 TI - [Analysis of the main ethical conflicts in the 2008 declaration of Helsinki and the proposed changes in the new version]. AB - The Declaration of Helsinki (DoH) of the World Medical Association is the basis of the rules governing research on human beings. The latest version (enacted in Korea, 2008) has been a source of ethical discussions, particularly regarding the use of placebos, the measures to assure the access of study subjects to interventions identified as beneficial once the study has ended, and the need of a better protection of potentially vulnerable groups. These issues led to draft a revised version, that was approved in 2013. In this paper, we present an ethical analysis of the main changes contained in the DoH, including the proposed changes in the new version, referring, when appropriate, to relevant Chilean laws governing research on human subjects. In our opinion, the 2008 DoH contains significant imprecisions on some of these issues, making a new version of the declaration necessary to fully protect subjects participating in biomedical research, as stated by the new version approved in 2013. PMID- 25117039 TI - [Postoperative delirium among older people]. AB - Delirium (acute confusional state) is a common and disabling complication among surgical older people. It is often underdiagnosed and undertreated. Its incidence varies by type of intervention and it is associated with several complications such as functional impairment, cognitive dysfunction, prolonged hospitalization and institutionalization. These increase hospitalization costs and the risk of death. There are precipitating and predisposing risk factors, which increase the susceptibility for postoperative delirium. This condition should be considered as a syndrome of epidemiological importance, which needs to be prevented or treated in a timely manner through a multidisciplinary intervention. The perioperative care of elderly patients involves different medical specialties and is a subject of general knowledge. PMID- 25117040 TI - [Use of Internet for mental health programs aimed at adolescents]. AB - BACKGROUND: The widespread use of INTERNET by adolescents, renders it a simple and accessible means for health care campaigns Aim: To perform a systematic review of ISI publications about INTERNET use for adolescent mental health prevention, detection, treatment or follow up. MATERIAL AND METHODS: Systematic reviews, meta analyses and controlled clinical trials in all languages were searched. Manuscripts without an abstract or only publishing the study design were excluded. All selected articles were critically read. RESULTS: One hundred and five papers were found and 61 were excluded because they did not address the research question. Of the resting 44, only six complied with the search criteria among then, 3 articles correspond to systematic reviews addressing early intervention programs and mental hearth treatment based on Internet; the other 3 articles correspond to controlled clinical trials addressing treatment interventions of anxiety and depression and 1 address on depression prevention program. CONCLUSIONS: INTERNET facilitates the application of mental health promotion, prevention and intervention among adolescents. However the resource is still underused. PMID- 25117041 TI - [A proposal for the definitive reform of the private health insurance system in Chile]. AB - Private health insurance should be able to provide coverage to people considered as high risk, such as women and the elderly. The only way to do that is to organize implicit or explicit cross-subsidies from low to high-risk individuals. This paper examines how European private health insurance companies introduced regulatory measures that could be introduced in Chile such as open enrollment, community-rated premiums, lifetime coverage, a package of minimum benefits and a risk equalization scheme. PMID- 25117042 TI - [Respecting patient intimacy]. AB - Transparency as a general rule for all our professional acts casts doubts about the statement of the Hippocratic Oath that says "Whatever I see or hear in the lives of my patients, I will keep secret, as considering all such things to be private". Medical secrecy protects the intimacy of patients, who reveal to their physicians their most hidden secrets aiming to recover their health. Therefore, physicians should receive those secrets with reverence and care, as servers and not as their owners. The values associated with the respect for personal intimacy are the anthropological basis of medical confidentiality. A medical act is performed by definition between two equally honorable individuals. Therefore, the professional honors the trust of his patient, maintaining strict confidence of what is revealed. Therefore, medical secrecy must be strengthened rather than weakened, pursuing common wealth and dignity. PMID- 25117043 TI - The role of the psychiatrist in obtaining informed consent from patients with somatic and mental comorbidity: Report of one case. AB - The nature of mental disorders, the attitudes and prejudices of the social community towards psychiatric patients, the behavior and treatment of mental patients, all bring about numerous dilemmas and prejudices. When a patient is diagnosed with a mental disorder, he may suffer restrictions in the field of general human rights. However, the biggest problems in clinical practice occur in the treatment of patients who, besides their mental disorder also have a somatic disease. We report a 56-years-old female with a severe renal failure who refused to undergo dialysis. Following the patient's refusal to sign an informed consent, a psychiatrist was called in for consultation and diagnosed an acute psychotic reaction. To manage the delusions and acute psychotic reactions, risperidone in the dose of 2 mg was started. After 22 days, the patient still had marked psychotic symptoms. A psychiatrist, a nephrologist and an anesthesiologist, in the presence of the spouse on the grounds of her life-threatening condition, decided to apply the necessary medical procedures even without the patient's consent. A day after the start of dialysis the patient still had delusional ideas, but without the presence of anxiety, and the patient no longer offered resistance to dialysis. Four days after the first dialysis, the patient was calm, had vague memories about the entire previous period, and signed the informed consent concerning her further treatment. PMID- 25117044 TI - [Sustained hematologic response in chronic eosinophilic leukemia with low dose imatinib. Report of one case]. AB - We report a 58 year-old-man without comorbid conditions, with a history of two months of weight loss, malaise and headache. His initial laboratory analysis showed leukocytosis of 16,100/mL with 65% eosinophils and an absolute eosinophil count of 10,465/mL. Both bone marrow biopsy and aspirate showed infiltration by mature appearing eosinophils. Treatment was started with hydroxyurea, associated with prednisone without satisfactory decrease in the eosinophil count. Polymerase chain reaction showed the presence of the gene fusion product FIP1L1/PDGFRA. Imatinib therapy was initiated, resulting in a rapid and progressive reduction in the absolute eosinophil count, with normalization at the second week of treatment. The incidence of the myeloproliferative variant causing hypereosinophilic syndrome is rare. However, the dramatic response to imatinib emphasizes the need to study the presence of the fusion product FIP1L1/PDGFRA in all patients with eosinophilia of unknown etiology. PMID- 25117045 TI - [First successful bridge to cardiac transplantation in Chile using the Heart Mate II device. Report of one case]. AB - Implantable ventricular assist devices are an effective treatment option for end stage heart failure patients as a bridge to cardiac transplantation, to improve the clinical condition and organ function allowing discharge from the hospital to await for transplantation. The second alternative is to use the device as destination therapy for patients with contraindications for cardiac transplantation, in whom it is maintained indefinitely. We report a 43-year-old patient, with a dilated cardiomyopathy, severe left ventricular dysfunction and advanced heart failure. A ventricular assist device Heart Mate II(c), as a bridge to transplantation, was implanted to the patient in the United States. It was explanted for the first time in Chile at the National Thorax Institute. Heart transplantation was performed using the bicaval technique. Induction of immunosuppression was done with basiliximab. Generic immunosuppression was carried out with cyclosporine, mycophenolate mofetil and prednisone. Postoperatively the patient evolved with right femoral vein thrombosis in the femoral cannulation site, phlegmasia alba dolens, rhabdomyolysis, oliguric acute renal failure, which required renal replacement therapy, severe shock, with high requirements of vasoactive drugs and need for mechanical ventilation. He required a reoperation for hemothorax and had an Enterobacter pneumonia. After a period of serious illness, he began a gradual recovery and was discharged from the hospital after 58 days. After two years, he remains in functional class I, with a normal graft function. PMID- 25117046 TI - [Granulomatous appendicitis caused by sarcoidosis: report of one case]. AB - Granulomatous appendicitis is uncommon and can be caused by Crohn's disease, foreign body reactions, infections or sarcoidosis. We report a 26-year-old female consulting in the emergency room for pain in the right lower abdomen. She was released with analgesics and consulted 14 days later for the same pain. This time she was operated with the preoperative diagnosis of appendicitis. The pathological study of the surgical piece was compatible with a granulomatous appendicitis caused by sarcoidosis. PMID- 25117047 TI - [Frederic Chopin (1810-1849), and his disease]. AB - Frederic Chopin - a great Polish composer and pianist-suffered from a chronic disease. Both during his life and after his death, physicians disagreed on Chopin's diagnosis. His contemporaries accepted the diagnosis of tuberculosis, a common disease in the 18th century. Description of new clinical entities provoked new dilemmas in the 21th century. Although other alternative diagnoses to tuberculosis have emerged, such as cystic fibrosis or alpha-1 antitrypsin deficiency, we still sustain that the first diagnosis is the most probable. In this paper we report F. Chopin's case history and discuss cons and pros for different diseases as the cause of F. Chopin's suffering and death. PMID- 25117050 TI - [Environmental effect on the incidence of Hantavirus cardiopulmonary syndrome in Chile]. PMID- 25117051 TI - [Centenary of the School of Public Health at Harvard University: Career and prestige]. PMID- 25117052 TI - [When you visit a doctor, do you hope that the doctor gives you one hour or only a few minutes?]. PMID- 25117053 TI - Bacterial community affects toxin production by Gymnodinium catenatum. AB - The paralytic shellfish toxin (PST)-producing dinoflagellate Gymnodinium catenatum grows in association with a complex marine bacterial community that is both essential for growth and can alter culture growth dynamics. Using a bacterial community replacement approach, we examined the intracellular PST content, production rate, and profile of G. catenatum cultures grown with bacterial communities of differing complexity and composition. Clonal offspring were established from surface-sterilized resting cysts (produced by sexual crosses of strain GCDE06 and strain GCLV01) and grown with: 1) complex bacterial communities derived from each of the two parent cultures; 2) simplified bacterial communities composed of the G. catenatum-associated bacteria Marinobacter sp. strain DG879 or Alcanivorax sp. strain DG881; 3) a complex bacterial community associated with an untreated, unsterilized sexual cross of the parents. Toxin content (STX-equivalent per cell) of clonal offspring (134-197 fmol STX cell(-1)) was similar to the parent cultures (169-206 fmol STX cell(-1)), however cultures grown with single bacterial types contained less toxin (134-146 fmol STX cell( 1)) than offspring or parent cultures grown with more complex mixed bacterial communities (152-176 fmol STX cell(-1)). Specific toxin production rate (fmol STX day(-1)) was strongly correlated with culture growth rate. Net toxin production rate (fmol STX cell(-1) day(-1)) did not differ among treatments, however, mean net toxin production rate of offspring was 8-fold lower than the parent cultures, suggesting that completion of the sexual lifecycle in laboratory cultures leads to reduced toxin production. The PST profiles of offspring cultures were most similar to parent GCDE06 with the exception of cultures grown with Marinobacter sp. DG879 which produced higher proportions of dcGTX2+3 and GC1+2, and lower proportions of C1+2 and C3+4. Our data demonstrate that the bacterial community can alter intracellular STX production of dinoflagellates. In G. catenatum the mechanism appears likely to be due to bacterial effects on dinoflagellate physiology rather than bacterial biotransformation of PST toxins. PMID- 25117054 TI - A new phenyl glycoside from the aerial parts of Equisetum hyemale. AB - A new phenyl glycoside, 2-(sophorosyl)-1-(4-hydroxyphenyl)ethanone (9), was isolated from the ethanolic extract of the aerial parts of Equisetum hyemale L., together with eight known compounds (1-8). The structures of these compounds were elucidated using a combination of spectroscopic analyses and chemical method. Of these nine compounds, 4 and 7 showed hepatoprotective effects towards tacrine induced cytotoxicity in Hep 3B cells with EC50 values of 42.7 +/- 1.5 and 132.6 +/- 2.8 MUM, respectively. PMID- 25117055 TI - Weak self-interactions of globular proteins studied by small-angle X-ray scattering and structure-based modeling. AB - We investigate protein-protein interactions in solution by small-angle X-ray scattering (SAXS) and theoretical modeling. The structure factor for solutions of bovine pancreatic trypsin inhibitor (BPTI), myoglobin (Mb), and intestinal fatty acid-binding protein (IFABP) is determined from SAXS measurements at multiple concentrations, from Monte Carlo simulations with a coarse-grained structure based interaction model, and from analytic approximate solutions of two idealized colloidal interaction models without adjustable parameters. By combining these approaches, we find that the structure factor is essentially determined by hard core and screened electrostatic interactions. Other soft short-ranged interactions (van der Waals and solvation-related) are either individually insignificant or tend to cancel out. The structure factor is also not significantly affected by charge fluctuations. For Mb and IFABP, with a small net charge and relatively symmetric charge distribution, the structure factor is well described by a hard-sphere model. For BPTI, with a larger net charge, screened electrostatic repulsion is also important, but the asymmetry of the charge distribution reduces the repulsion from that predicted by a charged hard-sphere model with the same net charge. Such charge asymmetry may also amplify the effect of shape asymmetry on the protein-protein potential of mean force. PMID- 25117057 TI - Intervention synthesis: a missing link between a systematic review and practical treatment(s). AB - Paul Glasziou and colleagues discuss methods to guide selection of an intervention from individual trials within a systematic review. Please see later in the article for the Editors' Summary. PMID- 25117059 TI - Chemical composition of essential oils and hydrosols from fresh flowers of Cerasus subhirtella and Cerasus serrulata from East China. AB - Essential oils and hydrosols from fresh flowers of Cerasus subhirtella (Miq.) Sok. and Cerasusserrulata (Lindl.) London from East China were analysed by gas chromatography and gas chromatography-mass spectrometry for the first time. The major components of the essential oils from C. subhirtella and C.serrulata were benzaldehyde (31.2% and 42.1%, respectively), tricosane (23.1% and 27.7%, respectively) and pentacosane (23.2% and 19.0%, respectively). The main constituents of the hydrosol volatiles from C. subhirtella and C.serrulata were benzaldehyde (67.5% and 64.3%, respectively) and mandelonitrile (12.5% and 12.4%, respectively). Benzaldehyde was the key component of the essential oils, while benzaldehyde as well as mandelonitrile was the principal compound of the hydrosols. PMID- 25117060 TI - Mesoscopic structuring and dynamics of alcohol/water solutions probed by terahertz time-domain spectroscopy and pulsed field gradient nuclear magnetic resonance. AB - Terahertz and PFG-NMR techniques are used to explore transitions in the structuring of binary alcohol/water mixtures. Three critical alcohol mole fractions (x1, x2, x3) are identified: methanol (10, 30, 70 mol %), ethanol (7, 15, 60 mol %), 1-propanol (2, 10, 50 mol %), and 2-propanol (2, 10, 50 mol %). Above compositions of x1 no isolated alcohol molecules exist, and below x1 the formation of large hydration shells around the hydrophobic moieties of the alcohol is favored. The maximum number of water molecules, N0, in the hydration shell surrounding a single alcohol molecule increases with the length of the carbon chain of the alcohol. At x2 the greatest nonideality of the liquid structure exists with the formation of extended hydrogen bonded networks between alcohol and water molecules. The terahertz data show the maximum absorption relative to that predicted for an ideal mixture at that composition, while the PFG-NMR data exhibit a minimum in the alkyl chain self-diffusivity at x2, showing that the alcohol has reached a minimum in diffusion when this extended alcohol water network has reached the highest degree of structuring. At x3 an equivalence of the alkyl and alcohol hydroxyl diffusion coefficients is determined by PFG NMR, suggesting that the molecular mobility of the alcohol molecules becomes independent of that of the water molecules. PMID- 25117058 TI - Aggressiveness of intensive care use among patients with lung cancer in the Surveillance, Epidemiology, and End Results-Medicare registry. AB - BACKGROUND: Approximately 65% of elderly patients with lung cancer who are admitted to the ICU will die within 6 months. Efforts to improve end-of-life care for this population must first understand the patient factors that underlie admission to the ICU. METHODS: We performed a retrospective cohort study examining all fee-for-service inpatient claims in the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry for elderly patients (aged > 65 years) who had received a diagnosis of lung cancer between 1992 and 2005 and who were hospitalized for reasons other than resection of their lung cancer. We calculated yearly rates of ICU admission per 1,000 hospitalizations via room and board codes or International Classification of Diseases, Ninth Revision, Clinical Modification and diagnosis-related group codes for mechanical ventilation, stratified the rates by receipt of mechanical ventilation and ICU type (medical/surgical/cardiac vs intermediate), and compared these rates over time. RESULTS: A total of 175,756 patients with lung cancer in SEER were hospitalized for a reason other than surgical resection of their tumor during the study period, 49,373 (28%) of whom had at least one ICU stay. The rate of ICU admissions per 1,000 hospitalizations increased over the study period from 140.7 in 1992 to 201.7 in 2005 (P < .001). The majority of the increase in ICU admissions (per 1,000 hospitalizations) between 1992 and 2005 occurred among patients who were not mechanically ventilated (118.2 to 173.3, P < .001) and among those who were in intermediate ICUs (20.0 to 61.9, P < .001), but increased only moderately in medical/surgical/cardiac units (120.7 to 139.9, P < .001). CONCLUSIONS: ICU admission for patients with lung cancer increased over time, mostly among patients without mechanical ventilation who were largely cared for in intermediate ICUs. PMID- 25117056 TI - Thiamine Deficiency-Mediated Brain Mitochondrial Pathology in Alaskan Huskies with Mutation in SLC19A3.1. AB - Alaskan Husky encephalopathy (AHE(1) ) is a fatal brain disease associated with a mutation in SLC19A3.1 (c.624insTTGC, c.625C>A). This gene encodes for a thiamine transporter 2 with a predominately (CNS) central nervous system distribution. Considering that brain is particularly vulnerable to thiamine deficiency because of its reliance on thiamine pyrophosphate (TPP)-dependent metabolic pathways involved in energy metabolism and neurotransmitter synthesis, we characterized the impact of this mutation on thiamine status, brain bioenergetics and the contribution of oxidative stress to this phenotype. In silico modeling of the mutated transporter indicated a significant loss of alpha-helices resulting in a more open protein structure suggesting an impaired thiamine transport ability. The cerebral cortex and thalamus of affected dogs were severely deficient in TPP dependent enzymes accompanied by decreases in mitochondrial mass and oxidative phosphorylation (OXPHOS) capacity, and increases in oxidative stress. These results along with the behavioral and pathological findings indicate that the phenotype associated with AHE is consistent with a brain-specific thiamine deficiency, leading to brain mitochondrial dysfunction and increased oxidative stress. While some of the biochemical deficits, neurobehavior and affected brain areas in AHE were shared by Wernicke's and Korsakoff's syndromes, several differences were noted likely arising from a tissue-specific vs. that from a whole-body thiamine deficiency. PMID- 25117062 TI - Reversible cerebral periventricular white matter changes with corpus callosum involvement in acute toluene-poisoning. AB - Substance poisoning, such as toluene intoxication, has seldom been reported in the relevant literature. The documented cerebral neuroimaging has mostly described reversible symmetrical white matter changes in both the cerebral and cerebellar hemispheres. This paper presents 2 patients with toluene poisoning, whose brain magnetic resonance imaging studies showed a similar picture that included extra involvement over the corpus callosum; however, such corpus callosum involvement has never been mentioned and is quite rare in the literature. We discussed the underlying neuropathological pathways in this article. Hopefully, these cases will provide first-line clinicians with some valuable information with regard to toluene intoxication and clinical neuroimaging presentations. PMID- 25117063 TI - Too fat, too thin: understanding bias against overweight and underweight in an Australian female university student sample. AB - OBJECTIVE: We compare attribution and social comparison theories as potential explanations for attitudes towards overweight and underweight targets among Australian university students. DESIGN: 185 female students (median age 18) completed a measure of body image state, then read one of six vignettes, describing a female student who was underweight, average weight or overweight, and who did or did not have a medical condition affecting weight. Independent variables were target weight (underweight, average-weight, overweight); weight controllability (no information, uncontrollable); and participant body image (higher, lower). MAIN OUTCOME MEASURES: Participants evaluated the target on six characteristics derived from existing research on weight bias, on seven-point Likert scales: attractive; healthy; likeable; motivated; self-disciplined; having willpower. RESULTS: A three-way between-participants multivariate analysis of covariance was conducted, with post hoc comparisons of significant effects. Overweight targets were rated more negatively than average-weight and underweight targets. Uncontrollability (medical) information produced more positive evaluations of the overweight target, but more negative evaluations of the underweight target. Ratings of the average-weight target were not influenced by uncontrollability information. Participant body image state had no significant effects. CONCLUSION: Results provided partial support for attribution theory, but not for social comparison theory, as an explanation of weight bias. PMID- 25117064 TI - Reverse-phase protein array for prediction of patients at low risk of developing bone metastasis from breast cancer. AB - BACKGROUND: A biomarker that predicts bone metastasis based on a protein laboratory assay has not been demonstrated. Reverse-phase protein array (RPPA) enables quantification of total and phosphorylated proteins, providing information about their functional status. The aim of this study was to identify bone-metastasis-related markers in patients with primary breast cancer using RPPA analysis. PATIENTS AND METHODS: Tumor samples were obtained from 169 patients with primary invasive breast carcinoma who underwent surgery. The patients were categorized by whether they developed breast cancer bone metastasis (BCBM) during follow-up. Clinical characteristics and protein expression by RPPA were compared and verified by leave-one-out cross-validation. RESULTS: Lymph node status (p = .023) and expression level of 22 proteins by RPPA were significantly correlated with BCBM in logistic regression analysis. These variables were used to build a logistic regression model. After filtering the variables through a stepwise algorithm, the final model, consisting of 8 proteins and lymph node status, had sensitivity of 30.0%, specificity of 90.5%, positive predictive value of 30.0%, and negative predictive value of 90.5% in the cross-validation. Most of the identified proteins were associated with cell cycle or signal transduction (CDK2, CDKN1A, Rb1, Src, phosphorylated-ribosomal S6 kinase, HER2, BCL11A, and MYH11). CONCLUSION: Our validated model, in which the primary tumor is tested with RPPA, can predict patients who are at low risk of developing BCBM and thus who likely would not benefit from receiving a bisphosphonate in the adjuvant setting. Clinical trials excluding these patients have the potential to clarify the benefit of bisphosphonates in the adjuvant setting. PMID- 25117066 TI - A community-based multicenter trial of pharmacokinetically guided 5-fluorouracil dosing for personalized colorectal cancer therapy. AB - BACKGROUND: Pharmacokinetically guided (PK-guided) versus body surface area-based 5-fluorouracil (5-FU) dosing results in higher response rates and better tolerability. A paucity of data exists on PK-guided 5-FU dosing in the community setting. PATIENTS AND METHODS: Seventy colorectal cancer patients, from one academic and five community cancer centers, received the mFOLFOX6 regimen (5-FU 2,400 mg/m(2) over 46 hours every 2 weeks) with or without bevacizumab at cycle 1. The 5-FU continuous-infusion dose was adjusted for cycles 2-4 using a PK guided algorithm to achieve a literature-based target area under the concentration-time curve (AUC). The primary objective was to demonstrate that PK guided 5-FU dosing improves the ability to achieve a target AUC within four cycles of therapy. The secondary objective was to demonstrate reduced incidence of 5-FU-related toxicities. RESULTS: At cycles 1 and 4, 27.7% and 46.8% of patients achieved the target AUC (20-25 mg * hour/L), respectively (odds ratio [OR]: 2.20; p = .046). Significantly more patients were within range at cycle 4 compared with a literature rate of 20% (p < .0001). Patients had significantly higher odds of not being underdosed at cycle 4 versus cycle 1 (OR: 2.29; p = .037). The odds of a patient being within range increased by 30% at each subsequent cycle (OR: 1.30; p = .03). Less grade 3/4 mucositis and diarrhea were observed compared with historical data (1.9% vs 16% and 5.6% vs 12%, respectively); however, rates of grade 3/4 neutropenia were similar (33% vs 25% 50%). CONCLUSION: PK-guided 5-FU dosing resulted in significantly fewer underdosed patients and less gastrointestinal toxicity and allows for the application of personalized colorectal cancer therapy in the community setting. PMID- 25117065 TI - Real-world study of everolimus in advanced progressive neuroendocrine tumors. AB - Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs. PMID- 25117067 TI - The association of hospital spending intensity and cancer outcomes: a population based study in an Asian country. AB - BACKGROUND: Different results are reported for the relationship between regional variation in medical spending and disease prognosis for acute illness and for cancer. Our objective was to investigate the association between hospital medical care spending intensity and mortality rates in cancer patients. METHODS: A total of 80,597 patients with incident cancer diagnosed in 2002 were identified from the National Health Insurance Research Database of Taiwan, Republic of China. The Cox proportional hazards model was used to compare the 5-year survival rates of patients treated at hospitals with different spending intensities after adjusting for possible confounding and risk factors. RESULTS: After adjustment for patient characteristics, treatment modality, and hospital volume, an association was found between lower hospital spending intensity and poorer survival rates. The 5 year survival rate expressed by hazard ratios was 1.36 (95% confidence interval [CI]: 1.30-1.43, p < .001) for colorectal cancer, 1.18 (95% CI: 1.08-1.29, p < .001) for lung cancer, 1.13 (95% CI: 1.05-1.22, p = .002) for hepatoma, 1.16 (95% CI: 1.07-1.26, p < .001) for breast cancer, and 1.23 (95% CI: 1.10-1.39, p = .001) for prostate cancer. CONCLUSION: Our preliminary findings indicate that higher hospital spending intensity was associated with lower mortality rates in patients being treated for lung cancer, breast cancer, colorectal cancer, prostate cancer, hepatoma, or head and neck cancer. The cancer stages were unavailable in this series, and more research linked with the primary data may be necessary to clearly address this issue. PMID- 25117069 TI - TGF-beta1 mediates estrogen receptor-induced epithelial-to-mesenchymal transition in some tumor lines. AB - More and more studies have reported that epithelial-mesenchymal transition (EMT) involved in the process of cancer development and progression occurs. The EMT also plays an important role in the movement and transfer of the tumors. Transforming growth factor-beta (TGF-beta) could induce the EMT in some cancer cell types. However, the mechanism underlying this transition process has also not been entirely clarified. In this study, the results indicated that TGF-beta1 mediated EMT in the tumor was associated with the estrogen receptor (ER). The decreased expression of vimentin and snail resulted in the decrease of the ER expression by small interfering RNA-mediated silencing and preventing the TGF beta-induced EMT. In conclusion, our results indicated that TGF-beta1 is an estrogen receptor signaling and essential novel downstream targets and could act as an important factor in the TGF-beta-induced EMT. PMID- 25117070 TI - MicroRNA-320a suppresses in GBM patients and modulates glioma cell functions by targeting IGF-1R. AB - Glioblastoma (GBM) is the most aggressive and malignant glioma. Currently, a few modern surgical and medical therapeutic strategies are applied for GBM, but the prognosis of GBM patients remains poor, and the average median survival time is only 14.6 months. In this study, we for the first time found that the levels of miR-320a were decreased in both GBM patients and glioma cells. In GBM patients, elevated miR-320a expression was associated with better prognosis. In addition, insulin-like growth factor-1 receptor (IGF-1R) was identified as a key direct target of miR-320a. Overexpression of miR-320a led to the inhibition of cell proliferation, migration, invasion, as well as tumorigenesis by targeting IGF-1R, and thus regulated the signaling pathways downstream, including PI3K/AKT and MAPK/ERK. In tumor orthotopic xenograft experiment, the tumor growth was depressed and survival time of mice model was prolonged when miR-320a was overexpressed. Therefore, our results suggested that miR-320a could suppress tumor development and growth by targeting IGF-1R, and miR-320a might serve as a new effective target for anti-cancer therapy strategies. PMID- 25117072 TI - Genetic variations of CAV1 gene contribute to HCC risk: a case-control study. AB - Hepatocellular carcinoma (HCC) is the sixth common cancer and the third common cause of cancer mortality worldwide. However, the exact molecular mechanism of HCC remains uncertain. Caveolin-1 (CAV1) is the main protein in the caveolin family and plays an important role in tumorigenesis signaling. However, the contribution of CAV1 genetic variants to HCC is still unknown. The purpose of this study was to evaluate the association between the tagSNPs of the CAV1 gene and HCC risk. In this case-control study, we enrolled 1,000 HCC patients and 1,000 cancer-free controls, which were frequency-matched by age, gender, and HBV infection status. We found that CAV1 rs729949 was statistically associated with increased risk of HCC (odds ratio (OR) = 1.28; 95% confidence interval (CI), 1.11 1.48; P = 8.53 * 10(-4)), even after Bonferroni correction (P = 5.97 * 10(-3)); the expression levels of CAV1 in cancer tissues were significantly lower than those in adjacent normal tissues (P = 0.012). We also detected a significant association for CAV1 rs3807989 under the log-additive model (OR = 0.85; 95% CI, 0.74-0.98; P = 0.026). Significant associations were also detected for CAV1 rs6466583 (GG vs AA: OR = 2.53; 95% CI, 1.24-5.17; P = 0.011) and CAV1 rs3807986 (AG vs AA: OR = 3.16; 95% CI, 1.68-5.91; P = 3.36 * 10(-4)) among genotype comparisons. These findings indicated that genetic variants n CAV1 might contribute to HCC susceptibility. PMID- 25117071 TI - Multifunctional CD40L: pro- and anti-neoplastic activity. AB - The CD40 ligand is a type I transmembrane protein that belongs to a tumor necrosis factor (TNF) superfamily. It is present not only on the surface of activated CD4+ T cells, B cells, blood platelets, monocytes, and natural killer (NK) cells but also on cancer cells. The receptor for ligand is constitutively expressed on cells, TNF family protein: CD40. The role of the CD40/CD40L pathway in the induction of body immunity, in inflammation, or in hemostasis has been well documented, whereas its involvement in neoplastic disease is still under investigation. CD40L ligand may potentiate apoptosis of tumor cells by activation of nuclear factor-kappaB (NF-kappaB), AP-1, CD95, or caspase-depended pathways and stimulate host immunity to defend against cancer. Although CD40L has a major contribution to anti-cancer activity, many reports point at its ambivalent nature. CD40L enhance release of strongly pro-angiogenic factor, vascular endothelial growth factor (VEGF), and activator of coagulation, TF, the level of which is correlated with tumor metastasis. CD40L involvement in the inhibition of tumor progression has led to the emergence of not only therapy using recombinant forms of the ligand and vaccines in the treatment of cancer but also therapy consisting of inhibiting platelets-main source of CD40L. This article is a review of studies on the ambivalent role of CD40L in neoplastic diseases. PMID- 25117068 TI - Advanced pancreatic cancer: flourishing novel approaches in the era of biological therapy. AB - The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin-like growth factor 1 receptor, transforming growth factor beta, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance. PMID- 25117073 TI - Expression of HSPA2 in human hepatocellular carcinoma and its clinical significance. AB - Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide. HSPA2 has been highlighted as an important marker in many types of cancers. However, little is known about the role of HSPA2 in HCC. The objective of the current study was to investigate the expression pattern and clinicopathological significance of HSPA2 in patients with HCC. Quantitative reverse-transcriptase ploymerase chain reaction (qRT-PCR) was applied to examine HSPA2 messenger RNA (mRNA) expression in 52 pairs of HCC tissues and adjacent noncancerous tissues. Immunohistochemistry (IHC) was performed to examine HSPA2 protein expression in paraffin-embedded tissues from 119 HCC patients. Statistical analyses were applied to evaluate the diagnostic value and associations of HSPA2 expression with clinicopathological characteristics. We identified abnormally elevated mRNA expression of HSPA2 in HCC tissues compared to paired adjacent noncancerous tissues (P < 0.001). Clinicopathological analysis showed that HSPA2 expression was significantly correlated with tumor size (P = 0.013), histological differentiation (P = 0.04), and tumor stage (P = 0.001). Patients with higher HSPA2 expression had shorter overall survival time, whereas those with lower HSPA2 expression had longer survival time. Furthermore, Cox regression analyses showed that HSPA2 expression was an independent predictor of overall survival. In conclusion, our findings provide evidences that positive expression of HSPA2 in HCC may be important in the acquisition of an aggressive phenotype and it is an independent biomarker for poor prognosis of patients with HCC. PMID- 25117077 TI - Phantom validation of Monte Carlo modeling for noncontact depth sensitive fluorescence measurements in an epithelial tissue model. AB - Experimental investigation and optimization of various optical parameters in the design of depth sensitive optical measurements in layered tissues would require a huge amount of time and resources. A computational method to model light transport in layered tissues using Monte Carlo simulations has been developed for decades to reduce the cost incurred during this process. In this work, we employed the Monte Carlo method to investigate the depth sensitivity achieved by various illumination and detection configurations including both the traditional cone configurations and new cone shell configurations, which are implemented by convex or axicon lenses. Phantom experiments have been carried out to validate the Monte Carlo modeling of fluorescence in a two-layered turbid, epithelial tissue model. The measured fluorescence and depth sensitivity of different illumination-detection configurations were compared with each other. The results indicate excellent agreement between the experimental and simulation results in the trends of fluorescence intensity and depth sensitivity. The findings of this study and the development of the Monte Carlo method for noncontact setups provide useful insight and assistance in the planning and optimization of optical designs for depth sensitive fluorescence measurements. PMID- 25117074 TI - Wnt/beta-catenin pathway in bone cancers. AB - The Wnt signaling pathway regulates some of the crucial aspects of cellular processes. The beta-catenin dependent Wnt signaling (Wnt/beta-catenin) pathway controls the expression of key developmental genes, and acts as an intracellular signal transducer. The association of Wnt/beta-catenin pathway is often reported with different cancers. In this study, we have reviewed the association of Wnt/beta-catenin pathway with bone cancers, focusing on carcinogenesis and therapeutic aspects. Wnt/beta-catenin pathway is a highly complex and unique signaling pathway, which has ability to regulate gene expression, cell invasion, migration, proliferation, and differentiation for the initiation and progression of bone cancers, especially osteosarcoma. Association of Wnt/beta-catenin pathway with chondrosarcoma, Ewing's sarcoma and chondroma is also documented. Recently, targeting Wnt/beta-catenin pathway has gained significant interests as a potential therapeutic application for the treatment of bone cancers. Small RNA technology to knockdown aberrant Wnt/beta-catenin or inhibition of beta-catenin expression by natural component has shown promising effects against bone cancers. Advances in understanding the mechanisms of Wnt signaling and new technologies have facilitated the discovery of agents that can target and regulate Wnt/beta catenin signaling pathway, and these may provide a basement for the innovative therapeutic approaches in the treatment of bone cancers. PMID- 25117075 TI - Polymorphism in interleukin 21 gene is associated with decreased susceptibility to diffuse large B cell lymphoma. AB - Interleukin 21 (IL-21) plays a key role in innate and adaptive immunity. Polymorphisms in IL-21 gene may be greatly involved in various diseases. The aim of the study was to investigate the association between IL-21 genetic polymorphisms and the susceptibility to diffuse large B cell lymphoma (DLBCL). IL 21 -2498G/A and +78A/G polymorphisms were examined in 221 DLBCL patients and 243 healthy controls. We found that distributions of -2498GA genotype and -2498AA genotype were clearly decreased in DLBCL cases compared to healthy donors (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.43-0.92, P = 0.021; OR = 0.36, 95 % CI = 0.15-0.48, P < 0.001; data were adjusted for age and sex). Stratification analyses revealed that patients with advanced Ann Arbor stages (III+IV) had further decreased percentage of -2498AA genotype than those with primary stages (OR = 0.31, 95% CI = 0.13-0.87, P = 0.023; data were adjusted for age and sex). In addition, we evaluated the possible effect of IL-21 polymorphisms on gene expression by examining serum level of IL-21 in patients and controls. Data revealed that subjects carrying -2498AA genotype had significantly higher serum level of IL-21 than those with GG genotype or GA genotype. These data suggest that IL-21 -2498G/A polymorphism is associated with decreased susceptibility to DLBCL and may increase serum level of IL-21. PMID- 25117078 TI - Real-time analysis of endogenous protoporphyrin IX fluorescence from delta aminolevulinic acid and its derivatives reveals distinct time- and dose-dependent characteristics in vitro. AB - Photodynamic therapy (PDT) and photodiagnosis based on the intracellular production of the photosensitizer protoporphyrin IX (PPIX) by administration of its metabolic precursor -aminolevulinic acid (ALA) achieved their breakthrough upon the clinical approval of MAL (ALA methyl ester) and HAL (ALA hexyl ester). For newly developed ALA derivatives or application in new tumor types, in vitro determination of PPIX formation involves multiparametric experiments covering variable pro-drug concentrations, medium composition, time points of analysis, and cell type(s). This study uses a fluorescence microplate reader with a built in temperature and atmosphere control to investigate the high-resolution long term kinetics (72 h) of cellular PPIX fueled by administration of either ALA, MAL, or HAL for each 10 different concentrations. For simultaneous proliferation correction, A431 cells were stably transfected with green fluorescent protein. The results indicate that the peak PPIX level is a function of both, incubation concentration and period: maximal PPIX is generated with 1 to 2-mM ALA/MAL or 0.125-mM HAL; also, the PPIX peak shifts to longer incubation periods with increasing pro-drug concentrations. The results underline the need for detailed temporal analysis of PPIX formation to optimize ALA (derivative)-based PDT or photodiagnosis and highlight the value of environment-controlled microplate readers for automated in vitro analysis. PMID- 25117079 TI - Aberration correction during real time in vivo imaging of bone marrow with sensorless adaptive optics confocal microscope. AB - We have demonstrated adaptive correction of specimen-induced aberration during in vivo imaging of mouse bone marrow vasculature with confocal fluorescence microscopy. Adaptive optics system was completed with wavefront sensorless correction scheme based on stochastic parallel gradient descent algorithm. Using image sharpness as the optimization metric, aberration correction was performed based upon Zernike polynomial modes. The experimental results revealed the improved signal and resolution leading to a substantially enhanced image contrast with aberration correction. The image quality of vessels at 38- and 75-MUm depth increased three times and two times, respectively. The corrections allowed us to detect clearer bone marrow vasculature structures at greater contrast and improve the signal-to-noise ratio. PMID- 25117080 TI - Zn(2+) effect on structure and residual hydrophobicity of amyloid beta-peptide monomers. AB - The aggregation of amyloid beta-peptide (Abeta peptide) has been associated with the pathogenesis of Alzheimer's disease (AD). In the present study, we aimed to disclose how Zn(2+) affects the Abeta aggregation in detail. Thus, molecular dynamics simulation was implemented to elucidate the changes of structure and residual hydrophobicity upon Zn(2+) coordination. Our results show that Zn(2+) can strongly influence the structural properties of Abeta40 and Abeta42 by reducing helical formation and increasing turn formation to expose the hydrophobic regions. Furthermore, hydrophobicity of Zn(2+)-Abeta40 and Zn(2+) Abeta42 was much higher than that of each monomer, since Zn(2+) binding can significantly influence the hydrophilic domains of Abeta. The further analyses indicate that not only four residues (H6, E11, H13, and H14) but also R5, D7, K16, K28, and terminal residues influence hydrophobicity upon Zn(2+) coordination. Importantly, R5, K16, and K28 play a crucial role to regulate solvation-free energies. This work is helpful to understand the fundamental role of Zn(2+) in aggregation, which could be useful for further development of new drugs to inhibit Zn(2+)-Abeta aggregation. PMID- 25117076 TI - Toward microendoscopy-inspired cardiac optogenetics in vivo: technical overview and perspective. AB - The ability to perform precise, spatially localized actuation and measurements of electrical activity in the heart is crucial in understanding cardiac electrophysiology and devising new therapeutic solutions for control of cardiac arrhythmias. Current cardiac imaging techniques (i.e. optical mapping) employ voltage- or calcium-sensitive fluorescent dyes to visualize the electrical signal propagation through cardiac syncytium in vitro or in situ with very high spatiotemporal resolution. The extension of optogenetics into the cardiac field, where cardiac tissue is genetically altered to express light-sensitive ion channels allowing electrical activity to be elicited or suppressed in a precise cell-specific way, has opened the possibility for all-optical interrogation of cardiac electrophysiology. In vivo application of cardiac optogenetics faces multiple challenges and necessitates suitable optical systems employing fiber optics to actuate and sense electrical signals. In this technical perspective, we present a compendium of clinically relevant access routes to different parts of the cardiac electrical conduction system based on currently employed catheter imaging systems and determine the quantitative size constraints for endoscopic cardiac optogenetics. We discuss the relevant technical advancements in microendoscopy, cardiac imaging, and optogenetics and outline the strategies for combining them to create a portable, miniaturized fiber-based system for all optical interrogation of cardiac electrophysiology in vivo. PMID- 25117083 TI - Emergency ultrasound: Leveling the training and assessment landscape. PMID- 25117084 TI - The impact of the Massachusetts health care reform on unpaid medical bills. AB - The Massachusetts health care reform was expected to reduce the financial burden of medical care, but literature exploring this effect is limited. In this study, we use hospital financial information and a panel data difference-in-difference model to assess the impact of the Massachusetts health care reform on unpaid medical bills. We find that the reform reduced the financial burden for patients, reflected by a 26percent decrease in hospital bad debt. The effect was more pronounced among safety-net hospitals, indicating a larger benefit for the most vulnerable population. PMID- 25117085 TI - Financial burden of medical out-of-pocket spending by state and the implications of the 2014 Medicaid expansions. AB - This study is the first to offer a detailed look at the burden of medical out-of pocket spending, defined as total family medical out-of-pocket spending as a proportion of income, for each state. It further investigates which states have greater shares of individuals with high burden levels and no Medicaid coverage but would be Medicaid eligible under the 2014 rules of the Affordable Care Act should their state choose to participate in the expansion. This work suggests which states have the largest populations likely to benefit, in terms of lowering medical spending burden, from participating in the 2014 adult Medicaid expansions. PMID- 25117081 TI - Heart failure care in low- and middle-income countries: a systematic review and meta-analysis. AB - BACKGROUND: Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs. METHODS AND FINDINGS: Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%-64%) of patients were treated with angiotensin converting enzyme inhibitors, 34% (95% CI: 28%-41%) with beta-blockers, and 32% (95% CI: 25%-39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%-7.7%) of total hospital admissions, and mean in hospital mortality was 8% (95% CI: 6%-10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified. CONCLUSIONS: The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors' Summary. PMID- 25117082 TI - Identification of cancer stem cells and a strategy for their elimination. AB - It has been established previously that up to 40% of mouse CD34(+) hematopoietic stem cells are capable of internalizing exogenous dsDNA fragments both in vivo and ex vivo. Importantly, when mice are treated with a combination of cyclophosphamide and dsDNA, the repair of interstrand crosslinks in hematopoietic progenitors is attenuated, and their pluripotency is altered. Here we show for the first time that among various actively proliferating mammalian cell populations there are subpopulations capable of internalizing dsDNA fragments. In the context of cancer, such dsDNA-internalizing cell subpopulations display cancer stem cell-like phenotype. Furthermore, using Krebs-2 ascites cells as a model, we found that upon combined treatment with cyclophosphamide and dsDNA, engrafted material loses its tumor-initiating properties which we attribute to the elimination of tumor-initiating stem cell subpopulation or loss of its tumorigenic potential. PMID- 25117086 TI - Demand for temporary agency nurses and nursing shortages. AB - There is an ongoing debate about the reasons for the growth of temporary employment of registered nurses (RNs). Some argue that efficiency incentives to increase flexibility and reduce labor costs are the principal cause, while others point to shortages of RNs as the stronger determinant. Using hospital-level data from California's Office of Statewide Health Planning and Development, we find a significant trend of increasing demand for agency nurses during the years of RN shortage. Demand rose with inpatient days, patient demand fluctuation, and the level of fringe benefits. Competition between hospitals and unionization, however, did not affect hospitals' demand for temporary RNs. PMID- 25117087 TI - Impact of CPOE usage on medication management process costs and quality outcomes. AB - We assess the impact of computerized physician order entry (CPOE) systems usage on cost and process quality in the medication management process. Data are compiled from 1,014 U.S. acute-care hospitals that have already implemented CPOE. Data sources include the American Hospital Association, HIMSS Analytics, and the Centers for Medicare and Medicaid Services. We examine the association of CPOE usage with nursing and pharmacy salary costs, and evidence-based medication process compliance. Empirical findings controlling for endogeneity in usage show that benefits accrue even when 100 percent usage is not achieved. We demonstrate that the relationship of CPOE usage with cost and compliance is non-linear. PMID- 25117088 TI - Polymorphisms in the DNA repair gene ERCC2/XPD and breast cancer risk: a HapMap based case-control study among Han Women in a Chinese less-developed area. AB - AIMS: Genetic variations in DNA repair genes may impact repair functions, DNA damage, and breast cancer risk. This study is aimed to assess the associations of genetic polymorphisms in excision repair cross-complementing group 2 (ERCC2) with the risk of developing breast cancer. MATERIALS AND METHODS: In total, 101 histopathologically confirmed breast cancer cases and 101 age/region-matched healthy controls were genotyped for rs 3916840, rs 1799793, and rs 238416 in ERCC2 by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The rs 238416 heterozygous GA genotype combined with the rs 238416 genotypes (GA+AA) showed a significant association with breast cancer susceptibility (corrected p<0.01, odds ratio [OR]=0.29, 95% confidence interval [CI]=0.15-0.54; corrected p<0.01, OR=0.31, 95% CI=0.17-0.56, respectively). The rs 238416 GA genotype carriers had a decreased risk of breast cancer. However, we observed no significant association between the rs 3916840 and rs 1799793 polymorphisms in ERCC2 and breast cancer risk. Moreover, haplotype analysis showed that the ACG haplotype was associated with a significantly decreased risk of breast cancer, whereas the GCG haplotype was associated with a significantly increased risk of breast cancer (corrected p=0.004 and p=0.002, respectively). Multifactor dimensionality reduction analysis demonstrated that the interactions between rs 3916840 and rs 238416 were significantly synergistic. CONCLUSION: To the best of our knowledge, this study is the first to demonstrate that the rs 238416 heterozygous genotype likely has a higher DNA repair capacity and, thus, can be protective against breast cancer in Chinese Han women. PMID- 25117089 TI - Interactions between voluntary and involuntary attention modulate the quality and temporal dynamics of visual processing. AB - Successfully navigating a dynamic environment requires the efficient distribution of finite neural resources. Voluntary (endogenous) covert spatial attention selectively allocates those processing resources to goal-relevant locations in the visual scene in the absence of eye movements. However, the allocation of spatial attention is not always voluntary; abrupt onsets in the visual periphery automatically enhance processing of nearby stimuli (exogenous attention). In dynamic environments, exogenous events and internal goals likely compete to determine the distribution of attention, but how such competition is resolved is not well understood. To investigate how exogenous events interact with the concurrent allocation of voluntary attention, we used a speed-accuracy trade-off (SAT) procedure. SAT conjointly measures the rate of information accrual and asymptotic discriminability, allowing us to measure how attentional interactions unfold over time during stimulus processing. We found that both types of attention sped information accrual and improved discriminability. However, focusing endogenous attention at the target location reduced the effects of exogenous cues on the rate of information accrual and rendered negligible their effects on asymptotic discriminability. We verified the robustness of these findings in four additional experiments that targeted specific, critical response delays. In conclusion, the speed and quality of visual processing depend conjointly on internally and externally driven attentional states, but it is possible to voluntarily diminish distraction by irrelevant events in the periphery. PMID- 25117090 TI - The role of mnemonic processes in pure-target and pure-foil recognition memory. AB - Surprisingly, response patterns in a recognition memory test are very similar regardless of whether the test list contains both targets and foils or just one class of items. To better understand these effects, we evaluate performance over the course of testing. Output interference (OI) is the decrease in performance across test trials due to an increase in noise caused by encoded test items. Critically, OI is predicted on pure lists if the mnemonic evidence for each test item is evaluated. In two experiments, participants received accurate feedback, no feedback, or random feedback that was unrelated to the response on each test trial and pure or standard test lists. When no feedback was provided, performance was nearly identical for standard and pure test lists, replicating previous findings. Only in the presence of accurate feedback were participants able to successfully adapt to pure list environments and improve their accuracy. Critically, OI was observed, demonstrating that participants continued to evaluate mnemonic evidence even in pure list conditions. We discuss the implication of these data for models of memory. PMID- 25117091 TI - The perception of Glass patterns by starlings (Sturnus vulgaris). AB - Glass patterns are structured dot stimuli used to investigate the visual perception of global form. Studies have demonstrated that humans and pigeons differ in their processing of circular versus linearly organized Glass patterns. To test whether this comparative difference is characteristic of birds as a phylogenetic class, we investigated for the first time how a passerine (starlings, Sturnus vulgaris) discriminated multiple Glass patterns from random dot stimuli in a simultaneous discrimination. By examining acquisition, steady state performance, and the effects of diminishing global coherence, it was found that the perception of Glass patterns by 5 starlings differed from human perception and corresponded to that established with pigeons. This suggests an important difference in how birds and primates are specialized in their processing of circular visual patterns, perhaps related to face perception, or in how these highly visual animals direct attention to the global and local components of spatially separated form stimuli. PMID- 25117092 TI - Analytical and clinical performance of a new point of care LABGEOIB D-dimer test for diagnosis of venous thromboembolism. AB - LABGEO(IB) D-dimer Test is a newly developed POC D-dimer assay and the first commercially available POC immunoassay instrument that exploits the disk rotation method for extraction of plasma. Citrate plasma was obtained from 201 apparently healthy subjects and 91 patients suspected for VTE, and their D-dimer level was measured by the LABGEO(IB) D-Dimer Test (LABGEO D-dimer) and HemosIL D-dimer test as a comparative method. To examine the effect of blood cells and anticoagulant, paired blood samples anticoagulated by heparin and citrate were obtained from various postoperative patients. The overall diagnostic performance of LABGEO(IB) D-dimer and HemosIL was comparable with similar area under ROC curve (p=0.79). The cut-off levels recommended by manufacturers (LABGEO D-dimer: 0.45 MUg/ml fibrinogen equivalent unit (FEU), HemosIL: 0.23 MUg/ml D-dimer unit (DDU)) and those yielding highest diagnostic efficiency (LABGEO D-dimer: 1.41 MUg/ml FEU; HemosIL: 0.85 MUg/ml DDU), were chosen for the evaluation. For LABGEO D-dimer negative predictive value (NPV), positive predictive value (PPV), sensitivity, specificity, and negative likelihood ratio (LR-neg) were 93-100%, 67-89%, 93 100%, 53-89% and 0.00-0.08. For HemosIL D-dimer, NPV, PPV, sensitivity, specificity and LR-neg were 90 - 100%, 76-95%, 89-100%, 70-96% and 0.00-0.12, all comparable to results for LABGEO D-dimer. LABGEO D-dimer test demonstrated acceptable performance when used for the VTE diagnostic work-up. PMID- 25117094 TI - Accumulation and absorption of serum amyloid A and apolipoprotein E fragments in the course of AA amyloidosis: a study in a mouse model. AB - Reactive AA amyloidosis develops secondary to chronic inflammatory disorders. Serum amyloid A protein (SAA) and its degradation products, named AAs, are the main components of amyloid deposits, while apolipoprotein E (apoE) fragments are the minor components. To further understand the molecular mechanism of AA amyloidosis, we examined SAA/AAs moieties and apoE in the spleen and plasma throughout the amyloid-generating and amyloid-absorbing phases in a mouse model. SAA and four AA species (8.5kDa, 7.8kDa, 7.0kDa, and 6.2kDa) were detected in the spleen. SAA and the 8.5 kDa and 7.8 kDa AAs were prominent in the acute phase, whereas the 7.0kDa AA, the second smallest AA corresponding to the most common form in the human disease, was prominent in the chronic phase. These results indicate that the higher molecular weight species first constituted the fibril, followed by the 7.0kDa species, which were finally absorbed. ApoE was a component of the amyloid deposits at a degradation size from the beginning and was absorbed without being converted to another size. Degradation products, either from SAA or apoE, did not appear in the plasma during the course of the disease. A more detailed understanding of the moieties of amyloid-related peptides may help in the development of a method that can indicate the disease activity of AA amyloidosis. PMID- 25117093 TI - The anti-cancer peptide, PNC-27, induces tumor cell necrosis of a poorly differentiated non-solid tissue human leukemia cell line that depends on expression of HDM-2 in the plasma membrane of these cells. AB - GOALS: We have developed the anti-cancer peptide, PNC-27, which is a membrane active peptide that binds to the HDM-2 protein expressed in the cancer cell membranes of solid tissue tumor cells and induces transmembrane pore formation in cancer, but not in normal cells, resulting in tumor cell necrosis that is independent of p53 activity in these cells. We now extend our study to non-solid tissue tumor cells, in this case, a primitive, possible stem cell human leukemia cell line (K562) that is also p53-homozygously deleted. Our purpose was twofold: to investigate if these cells likewise express HDM-2 in their plasma membranes and to determine if our anti-cancer peptide induces tumor cell necrosis in these non-solid tissue tumor cells in a manner that depends on the interaction between the peptide and membrane-bound HDM-2. PROCEDURES: The anti-cancer activity and mechanism of PNC-27, which carries a p53 aa12-26-leader sequence connected on its carboxyl terminal end to a trans-membrane-penetrating sequence or membrane residency peptide (MRP), was studied against p53-null K562 leukemia cells. Murine leukocytes were used as a non-cancer cell control. Necrosis was determined by measuring the lactate dehydrogenase (LDH) release and apoptosis was determined by the detection of Caspases 3 and 7. Membrane colocalization of PNC-27 with HDM-2 was analyzed microscopically using fluorescently labeled antibodies against HDM-2 and PNC-27 peptides. RESULTS: We found that K562 cells strongly express HDM-2 protein in their membranes and that PNC-27 co-localizes with this protein in the membranes of these cells. PNC-27, but not the negative control peptide PNC-29, is selectively cytotoxic to K562 cells, inducing nearly 100 percent cell killing with LDH release. In contrast, this peptide had no effect on the lymphocyte control cells. CONCLUSIONS: The results suggest that HDM-2 is expressed in the membranes of non-solid tissue tumor cells in addition to the membranes of solid tissue tumor cells. Since K-562 cells appear to be in the stem cell family, the results suggest that early developing tumor cells also express HDM-2 protein in their membranes. Since PNC-27 induces necrosis of K-562 leukemia cells and co localizes with HDM-2 in the tumor cell membrane as an early event, we conclude that the association of PNC-27 with HDM-2 in the cancer cell membrane results in trans-membrane pore formation which results in cancer cell death, as previously discovered in a number of different solid tissue tumor cells. Since K562 cells lack p53 expression, these effects of PNC-27 on this leukemia cell line occur by a p53-independent pathway. PMID- 25117095 TI - Calcium oxalate crystallization index (COCI): an alternative method for distinguishing nephrolithiasis patients from healthy individuals. AB - Urinary supersaturation triggers lithogenic crystal formation. We developed an alternative test, designated calcium oxalate crystallization index (COCI), to distinguish nephrolithiasis patients from healthy individuals based on their urinary crystallization capability. The effect of urine volume, oxalate, phosphate, citrate, potassium, and sodium on COCI values was investigated. COCI values were determined in 24-hr urine obtained from nephrolithiasis patients (n=72) and matched healthy controls (n=71). Increases in urine oxalate and phosphate and decreases in urine volume and citrate resulted in significantly increased COCI values. The urinary COCI in nephrolithiasis patients was significantly higher than that in healthy individuals. Two healthy subjects who had elevated COCI values were found to have asymptomatic kidney calculi. The receiver operating characteristic analysis showed an area under the curve of the urinary COCI test of 0.9499 (95%CI: 0.9131-0.9868) for distinguishing between nephrolithiasis and healthy subjects. At the cutoff of 165 mg oxalate equivalence/day, the urinary COCI test provided sensitivity, specificity, and accuracy amounts of 83.33%, 97.18%, and 90.21%, respectively. Urinary COCI values were primarily dependent on urine volume, oxalate, and phosphate. The test provided high sensitivity and specificity for clinically discriminating nephrolithiasis patients from healthy controls. It might be used to detect individuals with asymptomatic kidney calculi. PMID- 25117096 TI - Extracellular MCT4 is a possible indicator for skeletal muscle MHC fiber type change. AB - Biochemical markers that indicate fiber type rearrangement in myosin heavy chain (MHC) have been used to evaluate the effectiveness of exercise and/or rehabilitation therapy. The aim of this study was to investigate whether measures of extracellular monocarboxylate transporter 4 (MCT4) protein can help in the detection of MHC fiber type variation. Human skeletal muscle cells (HSkMCs) were succumbed to high atmospheric pressure. Immunoblot analyses were performed to evaluate MHC fiber type change, and an enzyme-linked immunosorbent assay system was developed for the quantification of MCT4 concentration. Static pressurization to HSkMCs resulted in an increase in cells of median diameter (18 MUm). The proportion of MHC Type I fiber was increased by pressurization, and MCT4 protein concentration in the culture medium was also increased in the pressurized sample. We conclude that the amount of MCT4 in culture medium released from HSkMCs reflects fiber type changes in MHC. PMID- 25117097 TI - Associations of single nucleotide polymorphisms related to insulin resistance with polycystic ovary syndrome. AB - BACKGROUND: We investigated and validated most of the hitherto-suggested polymorphisms for PCOS. MATERIALS AND METHODS: DNA samples from 359 pre menopausal Korean women with PCOS (n=196) and without (n=166) were analyzed by primer extension and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry using iPLEX Gold technology from Sequenom (Sequenom Inc, San Diego, CA, USA) to determine the genotypic frequency of 80 single nucleotide polymorphisms (SNPs) from the 49 genes. RESULTS: Four SNPs (rs10060745, rs1719889, rs680, rs705379) showed moderate association with a risk of PCOS. Three (rs1719889, rs680, and rs705379) out of four SNPs were related to insulin resistance. The rs705379 showed significant association with increased fasting glucose (p=0.045) and serum 2-h C-peptide level (p=0.026). The rs1719889 showed significant association with fasting glucose level (p=0.03). CONCLUSION: Our results provide evidence for the relationship between high prevalence of insulin resistance and PCOS. PMID- 25117098 TI - Life style intervention in moderately overweight individuals is associated with decreased levels of cathepsins L and S in plasma. AB - BACKGROUND: Adipose tissue cells produce cathepsins L and S, which have proatherogenic effects. Obesity is strongly linked to atherogenesis, cardiovascular morbidity, and mortality. OBJECTIVE: The aim of the present study was to see if life style interventions/weight reduction could decrease cathepsin L and S levels in blood plasma. METHOD: Study subjects (n=31) were recruited to a life style intervention program aiming at increased physical activity, more healthy eating habits, and weight reduction for most of the participants. Blood samples were collected at inclusion and after 4 and 8 weeks. RESULTS: Cathepsin L was significantly reduced at 4 weeks (p<0.0001) and 8 weeks (p=0.0004). A similar reduction was also seen for cathepsin S at 4 weeks (p=0.03) and 8 weeks (p=0.008). No significant change in fractalkine values was observed at 4 weeks (p=0.58), but a significant increase was apparent at 8 weeks (p=0.0002). CONCLUSION: The intervention program resulted in significant reductions of cathepsin L and S levels in plasma after 4 and 8 weeks of intervention. PMID- 25117099 TI - Correlation between low folate levels and hyperhomocysteinemia, but not with vitamin B12 in hypertensive patients. AB - INTRODUCTION: Hypertension is considered to be among the most important risk factors for cardiovascular and cerebrovascular diseases. In recent years, several investigators have reported that high plasma levels of total homocysteine (t-hcy) has a key role in the development of hypertension, and the deficiency of B complex vitamins could increase the risk of hypertension. The purpose of this study was to investigate the relationship between plasma homocysteine, folate and vitamin B12 in hypertensive patients. MATERIALS AND METHODS: In 116 patients with hypertension and 81 healthy subjects, total plasma homocysteine, vitamin B12 and folate levels were measured. RESULTS AND DISCUSSION: Homocysteine was significantly higher in patients than in control subjects (22.9+/-3.5 versus 9.0+/-2.3 MUmol/L respectively, p<0.001); the folate plasma concentrations in hypertensive patients were significantly lower than in control subjects (6.7+/ 5.0 ng/ml and 9.0+/-4.4 ng/ml respectively, p<0.05). Moreover, no differences in vitamin B12 plasma levels were observed when comparing the levels of hypertensive patients and those of the controls (440+/-223 pg/ml vs 491+/-185 pg/ml respectively, p>0.05). Our results confirmed that, as previously observed, elevated t-hcy levels and low folate levels, but not vitamin B12 levels, are significantly associated with hypertension. PMID- 25117100 TI - Higher sensitivity of capillary electrophoresis in detecting hemoglobin A2'compared to traditional gel electrophoresis. AB - HbA2' (also called Hb B2) is the most common delta-globin chain defect and is reported to occur in 1-2% of the African American population. The major clinical significance of HbA2' is that the failure to detect it might lead to an underestimation of the total HbA2, leading to failure to diagnose beta thalassemia minor. In order to diagnose beta-thalassemia minor, both HbA2 and HbA2' levels must be combined.Hb A2' accounts for a small percentage (1-2%) of the total hemoglobin in heterozygotes. It is difficult to detect this small amount by traditional gel electrophoresis. Using HPLC Hb A2' is easily detected as it produces a minor peak in the S window. Other conditions which might interfere with detection of HbA2' by HPLC include Hb S trait or Hb SS disease (Hb A2' hidden in the S peak), transfused Hb SS (Hb S peak may be very small), Hb C trait or Hb CC disease (glycosylated Hb C elutes in the S window), and Hb G (Hb G2 elutes in the S window). All of the above conditions, including Hb A2', occur most commonly in the same ethnic group (African American). We reviewed 654 consecutive cases over a period of three months for the presence of Hb A2' in our laboratory where capillary electrophoresis is used as the primary diagnostic tool. We detected seven cases (1.07 %) of HbA2'. In contrast, we did not detect any HbA2' using conventional gel electrophoresis in the last one year (2,580 cases). Although in none of the seven cases the sum of Hb A2 and Hb A2' exceeded 3.5%, we believe that capillary electrophoresis allows for a better detection of Hb A2' than gel electrophoresis and HPLC. PMID- 25117101 TI - ABCB1 expression in peptic ulcer patients and its connection with H. pylori Infection. AB - Glycoprotein P, encoded by the ABCB1 gene, plays an important role in gastric mucosa homeostasis and can influence the eradication therapy outcome in H. pylori infected individuals. In the study we examined the ABCB1 expression level in 128 peptic ulcer patients by real-time PCR. There was no correlation between gene expression and the presence of H. pylori or the H. pylori infection intensity. The expression level did not differ between women and men. However, the levels were higher in patients who were over 54 years old than those who were aged up to 54 years old. As ABCB1 expression is largely determined by genetic polymorphisms, in the future, expression data will be related to the patients' ABCB1 genotypes. PMID- 25117102 TI - Role of apolipoprotein AI gene polymorphism (G-75A and C+83T) in essential hypertension in Indian population. AB - Hypertension is becoming a public health emergency worldwide. It has been seen that both genetics and gene-environment interactions are major determinants of lipoprotein abnormalities and hypertension. This study elucidates the effect of apolipoprotein AI gene polymorphism (G-75A and C+83T) in 50 cases of essential hypertension and equal number of age & sex matched control subjects in the Indian population. Higher instances of obesity and more adverse biochemical profiles were found in hypertensives [GA (74%) and CT (56%) most commonly observed genotypes]. Presence of A and T alleles and GA (-75 bp) and CT (+83 bp) heterozygosity in apolipoprotein AI gene play an important role in essential hypertension (GA genotype had an odds ratio of 4.27 (1.69-10.96) of developing essential hypertension). The odds ratio for the GA genotype was 3.74 (95%CI, 0.83 9.0) in the presence of confounding factors including total proteins, albumin, amylase, cholesterol, triglycerides, LDL, VLDL and body mass index. It indicates one of the potential areas where population studies may be taken up for identifying the genetic basis of essential hypertension. PMID- 25117103 TI - Influence of iron regulating genes mutations on iron status in Egyptian patients with sickle cell disease. AB - Mutations of the HAMP gene and HFE gene have a role in iron overload. We assessed the frequency of the G71D mutation of the HAMP gene and the H63D mutation of the HFE gene and the correlation between these mutations as well as the correlation between them and the iron overload in sickle cell disease (SCD) patients. Genotyping of G71D of HAMP and of H63D of HFE variants was performed by polymerase chain reaction-restriction fragment length polymorphism on 47 SCD patients and 45 controls. The iron status was assessed by serum ferritin and transferrin saturation. We found 61.7% of the patients had a wild genotype in both genes, 14.9% had a variation in HAMP-G71D, 27.7% had a variation in HFE H63D, and 4.3% had variations in both. Patients with either HAMP-G71D or HFE-H63D variants did not show significant difference in iron status in comparison to patients with wild type genotypes. Multivariate regression analysis revealed that the number of mutations harbored by the patients tends to affect the serum ferritin level; p=0.07. Thus, The HAMP-G71D and HFE-H63D variants are not uncommon among the Egyptian SCD patients; neither of them alone was found to be a major determinant of iron overload in the studied patients. Nevertheless, the number of harboured mutations may increase the probability of iron overload in these patients. PMID- 25117104 TI - A cooperative approach to diagnosis of rare diseases: primitive myxoid mesenchymal tumor of infancy. AB - Primitive Myxoid Mesenchymal Tumor of Infancy (PMMTI) is a recently recognized locally aggressive myofibroblastic tumor. It is a low- to intermediate-grade fibroblastic malignancy with a high local recurrence rate but low metastatic potential and is composed of primitive spindled cells in a myxoid background. We present the eleventh reported case of PMMTI, occurring in the sinonasal tract of a 3-year old child. This case is novel in both the relatively older age of the child, the location of the tumor, and the role that immunohistochemical stains, and cytogenetic analysis played in differentiating it from similar diagnoses that differ considerably in their chemosensitivity and recurrence rates. Close collaboration between the pathologist and surgeon was crucial as different diagnoses would have led to vastly different treatment strategies for the patient. PMID- 25117106 TI - Traumatic neuroma of the anus after Milligan-Morgan hemorrhoidectomy. AB - There are several clinical settings of traumatic neuroma and a few may occur following surgical procedures. A 42-year-old man presented with anal pain five years after a Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids. A 4*4*3 mm sized anal polyp was seen during a rectal examination at a follow-up five years after surgery. The patient complained of point tenderness, pruritus, and anal discomfort as well as fecal retention. An endoscopy revealed a rectal polyp. Remarkably, histopathological examination and immunohistochemistry of the excised polyp showed a polypoid traumatic neuroma of the rectal plexus. After the excision of the polyp, the patient's complaint resolved completely. Traumatic neuromas may be a cause of significant pain and tenderness in patients with anal surgery or repair of anal lacerations. Interestingly, this is the second case of anal traumatic neuroma since Dr. Marks' first case in 1956 and is a possible complication of Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids. Similar complications of rectal surgery are reviewed. PMID- 25117105 TI - Two novel FAH gene mutations in a patient with hereditary tyrosinemia type I. AB - BACKGROUND: Hereditary tyrosinemia type I (HT I) is a severe inborn metabolic disorder affecting the tyrosine degradation pathway. Most untreated patients die within the first two years of life. HT I results from fumarylacetoacetate hydrolase (FAH) deficiency caused by mutations in the FAH gene. The diagnosis of HT I is confirmed by measuring FAH enzyme activity in cultured fibroblasts or liver tissue and/or detecting disease-causing mutations in the FAH gene. METHODS: A female neonate was referred to our hospital for further evaluation of an abnormal newborn screening test that showed elevated tyrosine levels. We analyzed amino acids and organic acids in the patient's blood and urine. To identify the genetic abnormality, all the coding exons and flanking introns of the FAH gene were analyzed via PCR. RESULTS: A repeat newborn screening test and plasma amino acid analysis revealed increased tyrosine levels in the patient. Urine organic acid analysis showed increased urinary excretion of 4-hydroxyphenyllactate, 4 hydroxyphenylpyruvate, and succinylacetone. Sequence analysis of the FAH gene identified two novel variations (c.536A>G (p.Gln179Arg) and c.913+5G>A) that had not been previously reported and that were not found in 170 healthy controls. CONCLUSIONS: HT I was confirmed in this patient by molecular genetic analysis of the FAH gene, with highly suggestive biochemical findings. The novel sequence variations detected in the present study should be considered disease-causing mutations by in silico analysis. In the Korean population, this is the first described case of HT I caused by a point mutation in the FAH gene. PMID- 25117107 TI - Hypercalcemia and renal failure in a young man: lessons in diagnosis. AB - Hypercalcemia is a common clinical problem. Morbidity and mortality associated with hypercalcemia are directly related to its underlying cause, making identification of the correct underlying etiology vital. When hypercalcemia is combined with acute kidney injury it points towards very specific diagnoses. We present a case of a young man with hypercalcemia and acute kidney injury who had multiple unusual laboratory findings that lead to the establishment of a correct diagnosis. PMID- 25117108 TI - Fresh frozen plasma as a source of cholesterol for newborn with Smith-Lemli-Opitz syndrome associated with defective cholesterol synthesis. AB - The Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive condition that is characterized by a mutation in the DHCR7 encoding the 7-dehydrocholesterol-Delta7 reductase, the enzyme that catalyzes the last step in cholesterol biosynthesis. The syndrome occurs in 1:20,000 newborns with an estimated gene carrier frequency in US Caucasian population of 1 to 2%. The severe form of SLOS in newborns leads to multiple malformations and mental retardation. The malformations present were facial dysmorphisms, cleft palate, congenital heart disease, genitourinary abnormalities, and syndactyly of the toes. The identification of the biochemical basis of SLOS has led to the development of therapeutic regimes based on dietary cholesterol supplementation. In this case report, we present a case of SLOS that was treated by fresh frozen plasma to increase the level of serum Cholesterol since oral and rectal cholesterol replacement was not possible in this instance. PMID- 25117109 TI - "20209C-T" a variant mutation of prothrombin gene mutation in a patient with recurrent pregnancy loss. AB - Recurrent pregnancy loss is considered when a female undergoes at least two consecutive, spontaneous abortions or more than two alternatively. This condition affects approximately 5% of women in reproductive age. Several causes of recurrent abortion have been established, but nevertheless, approximately half of all cases remain unexplained. Thrombophilic disorders have been suggested as a possible cause of recurrent miscarriage. A single 20210 G-A mutation of the 3' untranslated region of (F2) has been reported as a cause of inherited thrombophilia. The F2 G-A mutation affects 1% to 4% of the US population, and its prevalence is higher among Caucasian women of Southern European descendants. Studies of G20210A polymorphism have also shown conflicting associations with recurrent abortions. In addition to G20210A polymorphism, other mutations affecting the F2 gene have been associated with thrombosis and/or pregnancy complications. PMID- 25117111 TI - Shock Wave Induced Collapse of Arrays of Nanobubbles Located Next to a Lipid Membrane: Coarse-Grained Computer Simulations. AB - We used molecular dynamics simulations to study creation of pores in lipid bilayer membranes by inducing shock waves in systems containing arrays of nanobubbles next to these membranes. Shock waves impinged on the bubbles imploding them and produced nanojets that subsequently hit the bilayers making pores in them. Our simulations were performed using the MARTINI coarse-grained force field. The emphasis in our study was on the interaction of shock waves with two-bubble arrays when the bubbles were placed in different alignments. We observed that the largest damage to the bilayer was produced when two bubbles were positioned in a serial alignment and the bubbles touched each other. When two touching each other bubbles were located parallel to the membrane surface and at the same distance from the surface, the membrane damage was reduced, compared to the damage done by explosion of two independent nanobubbles. When two nanobubbles were placed in slanted configurations, the damage was intermediate between damages produced by two bubbles in parallel or serial alignment. Damage to the membrane produced by arrays containing more than two bubbles can be understood as a combination of damage produced by all three alignments of two bubbles. PMID- 25117114 TI - The aqueduct: William Sartain. PMID- 25117110 TI - Vitamin K deficiency bleeding leading to the diagnosis of Crohn's disease. AB - We report the case of a 45 year old man who came to Emergency Room of Polyclinic for sudden onset of localized ecchymosis and widespread hematomas. He was subjected to blood count and first level investigations to assess coagulation. Based on the results, second level investigations were performed. Endoscopy of the gastrointestinal tract with histological examination revealed a diagnosis of Crohn's disease. Vitamin K deficiency causes the formation of vitamin K-dependent clotting factors that cannot perform their pro-coagulant action. Consequently, patients present with hemorrhagic manifestations. Clinical and laboratory features observed in this patient show that the deficiency of vitamin K-dependent coagulation factors may reveal a complex clinical condition such as an inflammatory bowel disease. PMID- 25117115 TI - NIH's Undiagnosed Diseases Program expands: 6 new sites offer potential answers to more patients. PMID- 25117116 TI - Use of morcellation to remove fibroids scrutinized at FDA hearings. PMID- 25117126 TI - A piece of my mind. If these walls could talk. PMID- 25117127 TI - Flexible sigmoidoscopy for colorectal cancer screening: more evidence, persistent ironies. PMID- 25117128 TI - Meta-analysis as evidence: building a better pyramid. PMID- 25117129 TI - Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. AB - IMPORTANCE: Colorectal cancer is a major health burden. Screening is recommended in many countries. OBJECTIVE: To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 100,210 individuals aged 50 to 64 years, identified from the population of Oslo city and Telemark County, Norway. Screening was performed in 1999-2000 (55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending December 31, 2011. Of those selected, 1415 were excluded due to prior colorectal cancer, emigration, or death, and 3 could not be traced in the population registry. INTERVENTIONS: Participants randomized to the screening group were invited to undergo screening. Within the screening group, participants were randomized 1:1 to receive once-only flexible sigmoidoscopy or combination of once only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening test results (cancer, adenoma, polyp >=10 mm, or positive FOBT) were offered colonoscopy. The control group received no intervention. MAIN OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality. RESULTS: A total of 98,792 participants were included in the intention-to-screen analyses, of whom 78,220 comprised the control group and 20,572 comprised the screening group (10,283 randomized to receive a flexible sigmoidoscopy and 10,289 to receive flexible sigmoidoscopy and FOBT). Adherence with screening was 63%. After a median of 10.9 years, 71 participants died of colorectal cancer in the screening group vs 330 in the control group (31.4 vs 43.1 deaths per 100,000 person-years; absolute rate difference, 11.7 [95% CI, 3.0-20.4]; hazard ratio [HR], 0.73 [95% CI, 0.56-0.94]). Colorectal cancer was diagnosed in 253 participants in the screening group vs 1086 in the control group (112.6 vs 141.0 cases per 100,000 person-years; absolute rate difference, 28.4 [95% CI, 12.1 44.7]; HR, 0.80 [95% CI, 0.70-0.92]). Colorectal cancer incidence was reduced in both the 50- to 54-year age group (HR, 0.68; 95% CI, 0.49-0.94) and the 55- to 64 year age group (HR, 0.83; 95% CI, 0.71-0.96). There was no difference between the flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening groups. CONCLUSIONS AND RELEVANCE: In Norway, once-only flexible sigmoidoscopy screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence and mortality on a population level compared with no screening. Screening was effective both in the 50- to 54-year and the 55- to 64-year age groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00119912. PMID- 25117130 TI - Perioperative atrial fibrillation and the long-term risk of ischemic stroke. AB - IMPORTANCE: Clinically apparent atrial fibrillation increases the risk of ischemic stroke. In contrast, perioperative atrial fibrillation may be viewed as a transient response to physiological stress, and the long-term risk of stroke after perioperative atrial fibrillation is unclear. OBJECTIVE: To examine the association between perioperative atrial fibrillation and the long-term risk of stroke. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using administrative claims data on patients hospitalized for surgery (as defined by surgical diagnosis related group codes), and discharged alive and free of documented cerebrovascular disease or preexisting atrial fibrillation from nonfederal California acute care hospitals between 2007 and 2011. Patients undergoing cardiac vs other types of surgery were analyzed separately. MAIN OUTCOMES AND MEASURES: Previously validated diagnosis codes were used to identify ischemic strokes after discharge from the index hospitalization for surgery. The primary predictor variable was atrial fibrillation newly diagnosed during the index hospitalization, as defined by previously validated present-on-admission codes. Patients were censored at postdischarge emergency department encounters or hospitalizations with a recorded diagnosis of atrial fibrillation. RESULTS: Of 1,729,360 eligible patients, 24,711 (1.43%; 95% CI, 1.41%-1.45%) had new-onset perioperative atrial fibrillation during the index hospitalization and 13,952 (0.81%; 95% CI, 0.79%-0.82%) experienced a stroke after discharge. At 1 year after hospitalization for cardiac surgery, cumulative rates of stroke were 0.99% (95% CI, 0.81%-1.20%) in those with perioperative atrial fibrillation and 0.83% (95% CI, 0.76%-0.91%) in those without atrial fibrillation. At 1 year after noncardiac surgery, cumulative rates of stroke were 1.47% (95% CI, 1.24%-1.75%) in those with perioperative atrial fibrillation and 0.36% (95% CI, 0.35%-0.37%) in those without atrial fibrillation. In a Cox proportional hazards analysis accounting for potential confounders, perioperative atrial fibrillation was associated with subsequent stroke both after cardiac surgery (hazard ratio, 1.3; 95% CI, 1.1-1.6) and noncardiac surgery (hazard ratio, 2.0; 95% CI, 1.7-2.3). The association was significantly stronger for perioperative atrial fibrillation after noncardiac vs cardiac surgery (P < .001 for interaction). CONCLUSIONS AND RELEVANCE: Among patients hospitalized for surgery, perioperative atrial fibrillation was associated with an increased long-term risk of ischemic stroke, especially following noncardiac surgery. PMID- 25117131 TI - Association between analytic strategy and estimates of treatment outcomes in meta analyses. AB - IMPORTANCE: A persistent dilemma when performing meta-analyses is whether all available trials should be included in the meta-analysis. OBJECTIVES: To compare treatment outcomes estimated by meta-analysis of all trials and several alternative analytic strategies: single most precise trial (ie, trial with the narrowest confidence interval), meta-analysis restricted to the 25% largest trials, limit meta-analysis (a meta-analysis model adjusted for small-study effect), and meta-analysis restricted to trials at low overall risk of bias. DATA SOURCES: One hundred sixty-three meta-analyses published between 2008 and 2010 in high-impact-factor journals and between 2011 and 2013 in the Cochrane Database of Systematic Reviews: 92 (705 randomized clinical trials [RCTs]) with subjective outcomes and 71 (535 RCTs) with objective outcomes. DATA SYNTHESIS: For each meta analysis, the difference in treatment outcomes between meta-analysis of all trials and each alternative strategy, expressed as a ratio of odds ratios (ROR), was assessed considering the dependency between strategies. A difference greater than 30% was considered substantial. RORs were combined by random-effects meta analysis models to obtain an average difference across the sample. An ROR greater than 1 indicates larger treatment outcomes with meta-analysis of all trials. Subjective and objective outcomes were analyzed separately. RESULTS: Treatment outcomes were larger in the meta-analysis of all trials than in the single most precise trial (combined ROR, 1.13 [95% CI, 1.07-1.19]) for subjective outcomes and 1.03 (95% CI, 1.01-1.05) for objective outcomes). The difference in treatment outcomes between these strategies was substantial in 47 of 92 (51%) meta-analyses of subjective outcomes (meta-analysis of all trials showing larger outcomes in 40/47) and in 28 of 71 (39%) meta-analyses of objective outcomes (meta-analysis of all trials showing larger outcomes in 21/28). The combined ROR for subjective and objective outcomes was, respectively, 1.08 (95% CI, 1.04-1.13) and 1.03 (95% CI, 1.00-1.06) when comparing meta-analysis of all trials and meta-analysis of the 25% largest trials, 1.17 (95% CI, 1.11-1.22) and 1.13 (95% CI, 0.82-1.55) when comparing meta-analysis of all trials and limit meta-analysis, and 0.94 (95% CI, 0.86-1.04) and 1.03 (95% CI, 1.00-1.06) when comparing meta-analysis of all trials and meta-analysis restricted to trials at low risk of bias. CONCLUSIONS AND RELEVANCE: Estimation of treatment outcomes in meta-analyses differs depending on the strategy used. This instability in findings can result in major alterations in the conclusions derived from the analysis and underlines the need for systematic sensitivity analyses. PMID- 25117133 TI - Youth experimentation with e-cigarettes: another interpretation of the data. PMID- 25117132 TI - Treatment of hepatitis C: a systematic review. AB - IMPORTANCE: Hepatitis C virus (HCV) infects more than 185 million individuals worldwide. Twenty percent of patients chronically infected with HCV progress to cirrhosis. New, simpler therapeutics using direct-acting antivirals that target various stages of the HCV life cycle are in development to eradicate HCV without concomitant interferon. OBJECTIVES: To summarize published evidence on safety, efficacy (measured by a sustained virologic response [SVR], which is the treatment goal of undetectable plasma HCV RNA 12 or 24 weeks after therapy completion), and tolerability of current US Food and Drug Administration-approved interferon-based regimens and oral interferon-free regimens used for treating HCV infection and coinfection with human immunodeficiency virus (HIV) and HCV; to provide treatment recommendations for specialists and generalists based on published evidence. EVIDENCE REVIEW: A literature search of Web of Science, Scopus, Embase, Agricola, Cochrane Library, Cinahl Plus, ClinicalTrials.gov, Conference Papers Index, Gideon, PsycINFO, Google Scholar, and Oaister was conducted from January 1, 2009, to May 30, 2014. Publications describing phase 2, 3, and 4 studies evaluating the treatment of HCV were included. Forty-one studies involving 19,063 adult patients were included. Strength of clinical data and subsequent HCV treatment recommendations were graded according to the Oxford Centre for Evidence-Based Medicine. FINDINGS: Patients infected with HCV genotype 1 represent 60% to 75% of HCV infections in the United States. Hepatitis C virus genotype 1 is more difficult to cure than genotype 2 or genotype 3. Patients with HCV genotype 1 should receive treatment with sofosbuvir + pegylated interferon + ribavirin because of the shorter duration of therapy and high rates of SVR (89% 90%). Simeprevir + pegylated interferon + ribavirin is an alternative for patients with HCV genotype 1 (SVR, 79%-86%). Patients with HCV genotypes 2 and 3, representing 20% to 29% of US HCV infections, should receive therapy with sofosbuvir + ribavirin alone (SVR for genotype 2, 12 weeks' duration: 82%-93%; SVR for genotype 3, 24 weeks' duration, 80%-95%). Patients with HIV-HCV coinfection and patients with compensated cirrhosis (ie, cirrhosis but preserved synthetic liver function) should receive the same treatment as HCV-monoinfected patients. CONCLUSIONS AND RELEVANCE: New, short-duration, simpler therapies result in high SVR rates for HCV-infected patients. In conjunction with increased screening for HCV as suggested by recent Centers for Disease Control and Prevention guidelines, availability of new therapies may lead to the treatment of many more people with chronic HCV infection. PMID- 25117134 TI - Serum ammonia level for the evaluation of hepatic encephalopathy. PMID- 25117135 TI - Time to cardioversion for acute atrial fibrillation and thromboembolic complications. PMID- 25117136 TI - Risk and benefits of screening mammography. PMID- 25117137 TI - Risk and benefits of screening mammography--reply. PMID- 25117138 TI - Transparency in the delivery of mental health care. PMID- 25117139 TI - Transparency in the delivery of mental health care--reply. PMID- 25117140 TI - Hospital alarms and patient safety. PMID- 25117141 TI - Hospital alarms and patient safety--reply. PMID- 25117146 TI - Viral hepatitis--1975. PMID- 25117147 TI - JAMA patient page. Hepatitis C. PMID- 25117148 TI - Novel ABCC8 (SUR1) gene mutations in Asian Indian children with congenital hyperinsulinemic hypoglycemia. AB - Congenital hyperinsulinemic hypoglycemia (HI) is a heterogeneous genetic disorder of insulin secretion characterized by persistent hypoglycemia, most commonly associated with inactivating mutations of the beta-cell ATP-sensitive K(+) channel (K(ATP) channel) genes ABCC8 (encoding SUR1) and KCNJ11(encoding Kir6.2). This study aimed to screen the mutations in the genes associated with congenital HI in Asian Indian children. Recessive mutations of these genes cause hyperinsulinism that is unresponsive to treatment with channel agonists like diazoxide. Dominant K(ATP) mutations have been associated with diazoxide responsive disease. The KCNJ11, ABCC8, GCK, HNF4A, and GLUD1 genes were analyzed by sequence analysis in 22 children with congenital HI. We found 10 novel mutations (c.1delA, c.61delG, c.267delT, c.619-629delCCCGAGGACCT, Gln444*, Leu724Pro, Ala847Thr, Trp898*, IVS30-2A>C, and Leu1454Arg) and two known mutations (Gly111Arg and Arg598*) in the ABCC8 gene. This study describes novel and known ABCC8 gene mutations in children with congenital HI. This is the first large genetic screening study on HI in India and our results will help clinicians in providing optimal treatment for patients with hyperinsulinemia and in assisting affected families with genetic counseling. PMID- 25117149 TI - Likelihood ratio tests in rare variant detection for continuous phenotypes. AB - It is believed that rare variants play an important role in human phenotypes; however, the detection of rare variants is extremely challenging due to their very low minor allele frequency. In this paper, the likelihood ratio test (LRT) and restricted likelihood ratio test (ReLRT) are proposed to test the association of rare variants based on the linear mixed effects model, where a group of rare variants are treated as random effects. Like the sequence kernel association test (SKAT), a state-of-the-art method for rare variant detection, LRT and ReLRT can effectively overcome the problem of directionality of effect inherent in the burden test in practice. By taking full advantage of the spectral decomposition, exact finite sample null distributions for LRT and ReLRT are obtained by simulation. We perform extensive numerical studies to evaluate the performance of LRT and ReLRT, and compare to the burden test, SKAT and SKAT-O. The simulations have shown that LRT and ReLRT can correctly control the type I error, and the controls are robust to the weights chosen and the number of rare variants under study. LRT and ReLRT behave similarly to the burden test when all the causal rare variants share the same direction of effect, and outperform SKAT across various situations. When both positive and negative effects exist, LRT and ReLRT suffer from few power reductions compared to the other two competing methods; under this case, an additional finding from our simulations is that SKAT-O is no longer the optimal test, and its power is even lower than that of SKAT. The exome sequencing SNP data from Genetic Analysis Workshop 17 were employed to illustrate the proposed methods, and interesting results are described. PMID- 25117150 TI - ABCC5 transporter is a novel type 2 diabetes susceptibility gene in European and African American populations. AB - Numerous functional studies have implicated PARL in relation to type 2 diabetes (T2D). We hypothesised that conflicting human association studies may be due to neighbouring causal variants being in linkage disequilibrium (LD) with PARL. We conducted a comprehensive candidate gene study of the extended LD genomic region that includes PARL and transporter ABCC5 using three data sets (two European and one African American), in relation to healthy glycaemic variation, visceral fat accumulation and T2D disease. We observed no evidence for previously reported T2D association with Val262Leu or PARL using array and fine-map genomic and expression data. By contrast, we observed strong evidence of T2D association with ABCC5 (intron 26) for European and African American samples (P = 3E-07) and with ABCC5 adipose expression in Europeans [odds ratio (OR) = 3.8, P = 2E-04]. The genomic location estimate for the ABCC5 functional variant, associated with all phenotypes and expression data (P = 1E-11), was identical for all samples (at Chr3q 185,136 kb B36), indicating that the risk variant is an expression quantitative trait locus (eQTL) with increased expression conferring risk of disease. That the association with T2D is observed in populations of disparate ancestry suggests the variant is a ubiquitous risk factor for T2D. PMID- 25117152 TI - On the reliability of NMR relaxation data analyses: a Markov Chain Monte Carlo approach. AB - The analysis of NMR relaxation data is revisited along the lines of a Bayesian approach. Using a Markov Chain Monte Carlo strategy of data fitting, we investigate conditions under which relaxation data can be effectively interpreted in terms of internal dynamics. The limitations to the extraction of kinetic parameters that characterize internal dynamics are analyzed, and we show that extracting characteristic time scales shorter than a few tens of ps is very unlikely. However, using MCMC methods, reliable estimates of the marginal probability distributions and estimators (average, standard deviations, etc.) can still be obtained for subsets of the model parameters. Thus, unlike more conventional strategies of data analysis, the method avoids a model selection process. In addition, it indicates what information may be extracted from the data, but also what cannot. PMID- 25117151 TI - The efficacy of pad placement for electrical cardioversion of atrial fibrillation/flutter: a systematic review. AB - OBJECTIVES: Electrical cardioversion is commonly used to treat patients with atrial fibrillation and atrial flutter to restore normal sinus rhythm. There has been considerable debate as to whether the electrode placement affects the efficacy of electrical cardioversion. The objective of this study was to examine the effectiveness of anteroposterior (A-P) versus anterolateral (A-L) electrode placement to restore normal sinus rhythm. METHODS: A search of eight electronic databases, including Medline, EMBASE, CINAHL, and Cochrane was completed. Grey literature (hand-searching, Google, and SCOPUS) searching was also conducted. Studies were included if they were controlled clinical trials comparing the effectiveness of A-P versus A-L pad placement to restore normal sinus rhythm in adult patients with atrial fibrillation and flutter. Two independent reviewers judged study relevance, inclusion, and quality (e.g., risk of bias). Individual and pooled statistics were calculated as relative risks (RRs) with 95% confidence intervals (CIs) using a random-effects model, and heterogeneity (I(2) ) was reported. RESULTS: From 788 citations, 13 studies were included; seven involved monophasic, five involved biphasic, and one analyzed both waveform devices. The included studies tended to report cumulative success rates to restoring normal sinus rhythm after one to five sequential shocks of increasing energy; the number of shocks and energy used differed among studies. The risk of bias of the studies was "unclear." After the first shock, pad placement was not associated with an increased likelihood of restoring normal sinus rhythm (RR = 0.88; 95% CI = 0.73 to 1.06); however, heterogeneity was high (I(2) = 63%). Subgroup comparisons revealed that the A-L position was more effective (RR = 0.77; 95% CI = 0.59 to 1.00) at restoring normal sinus rhythm when using biphasic shocks (comparison p = 0.04). Overall, the pooled results failed to identify a difference between A-P and A-L pad placement in restoring normal sinus rhythm at any time (RR = 1.00; 95% CI = 0.95 to 1.05); however, heterogeneity was high (I(2) = 61%). No significant subgroup differences were found. Side effects were reported in only three studies. CONCLUSIONS: The published literature is restricted to persistent atrial fibrillation and atrial flutter, pad placement varied, and energy levels used were lower than currently recommended; however, the accumulated evidence suggests that electrical pad placement is not a critically important factor in successful cardioversion in atrial fibrillation and flutter (AF/AFL). A trial is urgently needed in recent-onset atrial fibrillation and atrial flutter patients using biphasic devices and high energy levels to resolve the debate. PMID- 25117153 TI - Dermatological toxicity associated with targeted therapies in cancer: optimal management. AB - Targeted therapies have developed rapidly over the last few years in the field of oncology thanks to a better understanding of carcinogenesis. They target pathways involved in signal transduction (EGFR, HER2, HER3, HER4, FLT3, RAS, RAF, MEK, KIT, RET, mTOR, SRC, EPH, SCF), tumor angiogenesis (VEGFR, TIE2), and tumor microenvironment (PDGFR, FGFR). They rarely cause the systemic adverse reactions generally associated with chemotherapy, but frequently cause disabling and specific skin toxicity. The impact on patient quality of life can be important both in terms of symptoms caused and of potentially aesthetic consequences. Inappropriate management can increase the risk of dose reduction or discontinuation of the cancer treatment. In this review, we will discuss skin toxicity associated with the main drug classes-EGFR, BRAF, MEK, mTOR, c-KIT, CTLA4, and SMO inhibitors, and anti-angiogenic agents. Targeted therapy-induced skin toxicities will be detailed in terms of symptoms, frequency, evolution, complications, and topical and oral treatments in order to improve their diagnosis and management. PMID- 25117154 TI - Neonatal junctional epidermolysis bullosa: treatment conundrums and ethical decision making. AB - Junctional epidermolysis bullosa (JEB), generalized severe (previously called JEB, Herlitz-type) has an extremely poor prognosis, with a mean age of death at 5 months old and most dead before age 3 years. We describe a typical case of a neonate with JEB who developed failure to thrive before his death from fungal septicemia at 4 months of age. This case highlights the ethical considerations of invasive treatments such as gastrostomy tube placements, intubations, and central line placements in neonates with JEB. We review the literature as well as discuss the ethical conundrums in the care of patients with JEB and other severe forms of epidermolysis bullosa. PMID- 25117156 TI - Mechanisms of action of oral emergency contraception. AB - This review gives an overview of the mechanisms of action of oral emergency contraception pills (ECPs), focusing on the levonorgestrel (LNG) and ulipristal acetate (UPA) containing ECPs. In vivo and in vitro studies have addressed the effect of EC on various possible targets. Based on these studies as well as on clinical trials it is clear that the efficacy of ECPs to prevent an unintended pregnancy depends on their mechanism of action as well as on their use in relation to the fertile window. While the main effect of both available ECPs is to prevent or delay ovulation the window of action for UPA is wider than that of LNG. This provides the biological explanation for the difference observed in clinical trials and the higher efficacy of UPA. Neither LNG nor UPA impairs endometrial receptivity or embryo implantation. Correct knowledge on the mechanism of action of ECPs is important to avoid overestimating their effectiveness and to advise women on correct use. PMID- 25117158 TI - Optimal older adult emergency care: introducing multidisciplinary geriatric emergency department guidelines from the American College of Emergency Physicians, American Geriatrics Society, Emergency Nurses Association, and Society for Academic Emergency Medicine. AB - In the United States and around the world, effective, efficient, and reliable strategies to provide emergency care to aging adults is challenging crowded emergency departments (EDs) and a strained health care system. In response, geriatric emergency medicine (EM) clinicians, educators, and researchers collaborated with the American College of Emergency Physicians (ACEP), American Geriatrics Society (AGS), Emergency Nurses Association (ENA), and the Society for Academic Emergency Medicine (SAEM) to develop guidelines intended to improve ED geriatric care by enhancing expertise, educational, and quality improvement expectations; equipment; policies; and protocols. These "Geriatric Emergency Department Guidelines" represent the first formal society-led attempt to characterize the essential attribute of the geriatric ED and received formal approval from the boards of directors for each of the four societies in 2013 and 2014. This article is intended to introduce EM and geriatric health care providers to the guidelines, while providing proposals for educational dissemination, refinement via formal effectiveness evaluations and cost effectiveness studies, and institutional credentialing. PMID- 25117155 TI - Hand sanitiser provision for reducing illness absences in primary school children: a cluster randomised trial. AB - BACKGROUND: The potential for transmission of infectious diseases offered by the school environment are likely to be an important contributor to the rates of infectious disease experienced by children. This study aimed to test whether the addition of hand sanitiser in primary school classrooms compared with usual hand hygiene would reduce illness absences in primary school children in New Zealand. METHODS AND FINDINGS: This parallel-group cluster randomised trial took place in 68 primary schools, where schools were allocated using restricted randomisation (1:1 ratio) to the intervention or control group. All children (aged 5 to 11 y) in attendance at participating schools received an in-class hand hygiene education session. Schools in the intervention group were provided with alcohol based hand sanitiser dispensers in classrooms for the winter school terms (27 April to 25 September 2009). Control schools received only the hand hygiene education session. The primary outcome was the number of absence episodes due to any illness among 2,443 follow-up children whose caregivers were telephoned after each absence from school. Secondary outcomes measured among follow-up children were the number of absence episodes due to specific illness (respiratory or gastrointestinal), length of illness and illness absence episodes, and number of episodes where at least one other member of the household became ill subsequently (child or adult). We also examined whether provision of sanitiser was associated with experience of a skin reaction. The number of absences for any reason and the length of the absence episode were measured in all primary school children enrolled at the schools. Children, school administrative staff, and the school liaison research assistants were not blind to group allocation. Outcome assessors of follow-up children were blind to group allocation. Of the 1,301 and 1,142 follow-up children in the hand sanitiser and control groups, respectively, the rate of absence episodes due to illness per 100 child-days was similar (1.21 and 1.16, respectively, incidence rate ratio 1.06, 95% CI 0.94 to 1.18). The provision of an alcohol-based hand sanitiser dispenser in classrooms was not effective in reducing rates of absence episodes due to respiratory or gastrointestinal illness, the length of illness or illness absence episodes, or the rate of subsequent infection for other members of the household in these children. The percentage of children experiencing a skin reaction was similar (10.4% hand sanitiser versus 10.3% control, risk ratio 1.01, 95% CI 0.78 to 1.30). The rate or length of absence episodes for any reason measured for all children also did not differ between groups. Limitations of the study include that the study was conducted during an influenza pandemic, with associated public health messaging about hand hygiene, which may have increased hand hygiene among all children and thereby reduced any additional effectiveness of sanitiser provision. We did not quite achieve the planned sample size of 1,350 follow-up children per group, although we still obtained precise estimates of the intervention effects. Also, it is possible that follow-up children were healthier than non-participating eligible children, with therefore less to gain from improved hand hygiene. However, lack of effectiveness of hand sanitiser provision on the rate of absences among all children suggests that this may not be the explanation. CONCLUSIONS: The provision of hand sanitiser in addition to usual hand hygiene in primary schools in New Zealand did not prevent disease of severity sufficient to cause school absence. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609000478213. Please see later in the article for the Editors' Summary. PMID- 25117159 TI - Non-infectious skin disease in Indigenous Australians. AB - The burden of non-infectious skin disease in the Indigenous Australian population has not been previously examined. This study considers the published data on the epidemiology and clinical features of a number of non-infectious skin diseases in Indigenous Australians. It also outlines hypotheses for the possible differences in the prevalence of such diseases in this group compared with the general Australian population. There is a paucity of literature on the topic but, from the material available, Indigenous Australians appear to have a reduced prevalence of psoriasis, type 1 hypersensitivity reactions and skin cancer but increased rates of lupus erythematosus, kava dermopathy and vitamin D deficiency when compared to the non-Indigenous Australian population. This article profiles the prevalence and presentation of non-infectious skin diseases in the Indigenous Australian population to synthesise our limited knowledge and highlight deficiencies in our understanding. PMID- 25117160 TI - Surgical gem: island advancement flaps for lip reconstruction. AB - Island advancement flaps provide specific advantages for repairing certain defects on the upper lip. We discuss the design and execution of this flap for defects on the alar sill and philtrum. PMID- 25117161 TI - A case of abatacept associated neutrophilic dermatosis and a review of the literature. AB - Abatacept is a novel biological agent that dampens the immune response by blocking the co-stimulation of T-cells, thus downregulating T-cell activation. It is currently approved for the treatment of rheumatoid arthritis (RA). The group of novel immunomodulatory agents, referred to as biologics, have now been used extensively, with established safety and side-effect profiles. There are, however, increasing reports of adverse paradoxical reactions, most notably resulting from anti-tumour necrosis factor (TNF) therapy. While cutaneous adverse reactions to abatacept are rare, there are a few reports of such paradoxical reactions. We report a case of an idiosyncratic paradoxical neutrophilic dermatosis associated with the use of abatacept. PMID- 25117162 TI - Emergence of chemoresistance in a metastatic basal cell carcinoma patient after complete response to hedgehog pathway inhibitor vismodegib (GDC-0449). AB - Vismodegib (GDC-0449, Genentech, USA), a small molecule inhibitor of the Hedgehog signalling pathway, has potent anti-tumour activity in advanced basal cell carcinoma (BCC). We report a case of a 67-year-old Australian man with metastatic BCC including pulmonary disease with malignant effusion who showed a dramatic complete response to vismodegib but subsequently experienced a recurrence of pulmonary disease, indicative of chemoresistance to vismodegib. This case is the first to illustrate chemoresistance in a patient with metastatic BCC, and demonstrates the need for closely monitoring metastatic BCC patients even after an apparently complete response. PMID- 25117163 TI - Isotretinoin and night blindness. AB - Isotretinoin is an effective and increasingly popular treatment for acne vulgaris. There have been reports of night blindness as a side-effect of treatment although the evidence does not demonstrate a clear causal relationship between isotretinoin therapy and the risk of night blindness. Nevertheless, considering the lack of evidence in this area, it is important to educate patients about this potential consequence, which may become longstanding and even irreversible, and encourage them to promptly report changes in their night vision. PMID- 25117165 TI - Montague B Lewis. PMID- 25117166 TI - Abdomino-pelvic actinomycetoma successfully treated with combination chemotherapy. PMID- 25117167 TI - A novel mutation of CYLD gene in a Chinese family with multiple familial trichoepithelioma. PMID- 25117168 TI - Delayed onset perforating folliculitis associated with sorafenib. PMID- 25117169 TI - Pregnancy outcomes of two patients exposed to ustekinumab in the first trimester. PMID- 25117170 TI - Pretibial fever: a forgotten cause of erythema nodosum. PMID- 25117171 TI - Comedonal Darier's disease diagnosed incidentally in a patient undergoing a routine skin examination for sun cancer. PMID- 25117172 TI - Involvement of oxidative stress in the mechanism of cadmium-induced toxicity on rat uterus. AB - The study was undertaken to explore whether cadmium bioaccumulation can induce oxidative stress in the uterus of rats. Cadmium (0.09, 0.9, 1.8 or 4.5mgCd/kg b.w.) was administered by gavage for 28 days. The animals were dissected on the first day and then after 90 days post exposure (second group of animals). The results show that cadmium accumulates in the uterus in a dose-dependent manner. The uterine Cd concentrations were almost the same in both groups, which is indicative of its long half-life in this organ. The accumulated cadmium caused significant changes in catalase (CAT) activity and lipid peroxidation (MDA) levels at concentrations from 0.09 to 0.35MUgCd/g wet uterine tissue. In summary our results show that the induction of oxidative stress and lipid peroxidation in the uterus may play important roles in the mechanism of toxicity in this organ and may have a negative impact on reproductive processes. PMID- 25117174 TI - Can enrichment make Brazilian tapir spend more time on view to the public? AB - One common visitor complaint in zoos is that the nonhuman animals are not visible. This problem needs to be resolved without compromising the animals' welfare; environmental enrichment could solve the problem. This study investigated whether enrichment would increase public exposure time of lowland tapir (Tapirus terrestris) in the Belo Horizonte Zoo in Minas Gerais, Brazil. Observations were made before (62 hr) and during (62 hr) the introduction of enrichment using focal animal sampling with instantaneous recording of behavior. The 5 enrichment items were a bamboo fence covered in vines, logs, a sandbox, dry leaves, and bamboo bushes. Before the enrichments were applied, the tapir was not visible to the public for more than 85% of the time. In addition, during the analysis of the enrichment treatment, other variables were considered--such as weekday, time of day, and weather conditions--which could influence the animals' interaction with the enrichments. The enrichments increased and decreased the expression of some behaviors; however, public viewing time of the animals did not increase. Thus, the enrichment applied was not strong enough to overcome the animals' crepuscular behavior. PMID- 25117173 TI - The pharmacokinetics of daclatasvir and asunaprevir administered in combination in studies in healthy subjects and patients infected with hepatitis C virus. AB - BACKGROUND AND OBJECTIVES: The combination of direct-acting antiviral agents in patients with chronic hepatitis C virus (HCV) infection has demonstrated clinical benefit; however, evaluation of potential drug-drug interactions is required prior to therapy. METHODS: An open-label study assessed the pharmacokinetics and tolerability of the HCV NS5A replication complex inhibitor daclatasvir and the HCV NS3 protease inhibitor asunaprevir when co-administered in healthy subjects. Daclatasvir 60 mg once daily and asunaprevir 600 mg twice daily were dosed for 7 days alone followed by combination dosing for 14 days at 30 mg once daily and 200 mg twice daily, respectively. Further assessments were provided comparing exposures from the current study with those from studies in HCV-infected patients receiving either the same or higher doses of daclatasvir or asunaprevir administered alone or together. RESULTS: Dose-normalized daclatasvir and asunaprevir morning exposures were comparable with control in healthy subjects, with geometric mean area under the concentration-time curve ratios of 1.202 (90 % CI 1.113-1.298) and 0.868 (90 % CI 0.726-1.038), respectively. In HCV patients daclatasvir and asunaprevir exposures were largely comparable, when administered together or alone. CONCLUSIONS: Additional data support the conclusion that there is no clinically meaningful interaction between daclatasvir and asunaprevir in either healthy subjects or HCV-infected patients, including those also receiving peginterferon-alpha/ribavirin, and that the combination of daclatasvir 60 mg once daily and asunaprevir 200 mg twice daily is generally well-tolerated. PMID- 25117175 TI - A case of painless acute Type-A thoracic aortic dissection. AB - We describe the case of an 83-year-old lady with a known aneurysmal thoracic aorta, developing acute breathlessness and hypoxia, with no pain and unremarkable cardiovascular examination. As D-dimers were raised, she was treated with low molecular-weight heparin (LMWH) for suspected pulmonary embolism. CT pulmonary angiography showed acutely dissecting, Type-A, thoracic aortic aneurysm. The patient was treated medically with beta-blockers. Despite a poor prognosis, she remains well 2 months later. Observational studies of patients over 70 with Type A dissection show only 75.3% experience pain, are offered surgery less and have higher mortality. d-Dimers are almost always elevated in aortic dissection. No previous studies document breathlessness as the only presenting symptom. This case emphasises the need, in older populations, for a low suspicion threshold for aortic dissection. PMID- 25117176 TI - Individualized quality of life in patients with low back pain: reliability and validity of the Patient Generated Index. AB - OBJECTIVE: To evaluate the reliability and validity of the improved version of the Patient Generated Index (PGI) in patients with low back pain. METHODS: The PGI was administered to 90 patients attending care in 1 of 6 institutions in Norway and evaluated for reliability and validity. The questionnaire was given out to 61 patients for re-test purposes. RESULTS: The PGI was completed correctly by 80 (88.9%) patients and, of the 61 patients responding to the re-test, 50 (82.0%) completed both surveys correctly. PGI scores were approximately normally distributed, with a median of 40 (range 80), where 100 is the best possible quality of life. There were no floor or ceiling effects. The 5 most frequently listed areas affecting quality of life were pain, sleep, stiffness, socializing and housework. The test-retest intraclass correlation coefficient was 0.73. The smallest detectable changes for individual and group purposes were 32.8 and 4.6, respectively. The correlations between PGI scores and other instrument scores followed a priori hypotheses of low to moderate correlations. DISCUSSION: The PGI has evidence for reliability and validity in Norwegian patients with low back pain at the group level and may be considered for application in intervention studies when a comprehensive evaluation of quality of life is important. However, the smallest detectable change, of approximately 30 points, may be considered too large for individual purposes in clinical applications. PMID- 25117178 TI - Heart failure: gaps in knowledge and failures in treatment. AB - Please see later in the article for the Editors' Summary. PMID- 25117180 TI - Seniors' body weight dissatisfaction and longitudinal associations with weight changes, anorexia of aging, and obesity: results from the NuAge Study. AB - OBJECTIVE: We examined longitudinal associations between weight dissatisfaction, weight changes, anorexia of aging, and obesity among 1,793 seniors followed over 4 years between 2003 and 2009. METHOD: Obesity prevalence (body mass index [BMI] >= 30) and prevalence/incidence of weight dissatisfaction, anorexia of aging (self-reported appetite loss), and weight changes >=5% were assessed. Predictors of weight loss >=5%, anorexia of aging, and weight dissatisfaction were examined using logistic regressions. RESULTS: Half of seniors experienced weight dissatisfaction (50.6%, 95% confidence interval [CI] = [48.1, 53.1]). Anorexia of aging and obesity prevalence was 7.0% (95% CI = [5.7, 8.3]) and 25.1% (95% CI = [22.9, 27.3]), whereas incidence of weight gain/loss >=5% was 6.6% (95% CI = [1.3, 11.9]) and 8.8% (95% CI = [3.3, 14.3]). Weight gain >=5% predicts men's subsequent weight dissatisfaction (odds ratio [OR] = 6.66, 95% CI = [2.06, 21.60]). No other association was observed. DISCUSSION: Weight dissatisfaction is frequent but not associated with subsequent eating disorders. In men, weight gain predicted weight dissatisfaction. Seniors' weight dissatisfaction does not necessarily equate weight changes. Due to its high prevalence, it is of public health interest to understand how seniors' weight dissatisfaction may impact health. PMID- 25117181 TI - Predictors of injurious falls and fear of falling differ: an 11-year longitudinal study of incident events in older people. AB - OBJECTIVE: The objective of the study is to identify the intrinsic, psychosocial and lifestyle factors, which, over time, predict the incidence of having a fall requiring medical attention (injurious fall) or of acquiring a fear of falling (FOF). METHOD: Data from 1,000 participants in the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA, 1994-2005) were analyzed using cox regressions and hazard ratios. RESULTS: The predictors of injurious falls (n = 900, events = 200) were increasing age, slower gait speed, and being depressed. Main predictors of developing a FOF (n = 855, events =117) were increasing age, cognitive impairment, reduced social activity, and gender. A history of falls at baseline did not predict acquiring a FOF nor did FOF predict a future fall. DISCUSSION: The profile of the person who will have an injurious fall differs from the profile of the person who develops a FOF and should be considered when designing interventions. PMID- 25117182 TI - Untargeted mass spectrometry-based metabolomic profiling of pleural effusions: fatty acids as novel cancer biomarkers for malignant pleural effusions. AB - Untargeted mass spectrometry-based metabolomic profiling is a powerful analytical method used for broad-spectrum identification and quantification of metabolites in biofluids in human health and disease states. In this study, we exploit metabolomic profiling for cancer biomarker discovery for diagnosis of malignant pleural effusions. We envisage the result will be clinically useful since currently there are no cancer biomarkers that are accurate enough for the diagnosis of malignant pleural effusions. Metabolomes of 32 malignant pleural effusions from lung cancer patients and 18 benign effusions from patients with pulmonary tuberculosis were analyzed using reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS) using AB SCIEX TripleTOF 5600. MS spectra were analyzed using XCMS, PeakView, and LipidView. Metabolome-Wide Association Study (MWAS) was performed by Receiver Operating Characteristic Curve Explorer and Tester (ROCCET). Insignificant markers were filtered out using a metabolome wide significance level (MWSL) with p-value < 2 * 10(-5) for t test. Only compounds in Human Metabolome Database (HMDB) will be used as cancer biomarkers. ROCCET analysis of ESI positive and negative MS spectra revealed free fatty acid (FFA) 18:1 (oleic acid) had the largest area-under-ROC of 0.96 (95% CI = 0.87 1.00) in malignant pleural effusions. Using a ratio of FFA 18:1-to-ceramide (d18:1/16:0), the area-under-ROC was further increased to 0.99 (95% CI = 0.91 1.00) with sensitivity 93.8% and specificity 100.0%. Using untargeted metabolomic profiling, the diagnostic cancer biomarker with the largest area-under-ROC can be determined objectively. This lipogenic phenotype could be explained by overexpression of fatty acid synthase (FASN) in cancer cells. The diagnostic performance of FFA 18:1-to-ceramide (d18:1/16:0) ratio supports its use for diagnosis of malignant pleural effusions. PMID- 25117185 TI - What do people want? Factors people consider when acquiring dogs, the complexity of the choices they make, and implications for nonhuman animal relocation programs. AB - A survey was conducted to assess decisions people make when acquiring dogs, including what sources they consider, the importance of the variety of dogs available, and their willingness to travel to adopt dogs of their choice. A conjoint design was used to ask each respondent to rate his or her likelihood of acquiring a dog based on a "profile" that included attributes such as age, size, and color as well as where the dog came from and euthanasia risk. Overall, these results showed that people preferred variety and would drive distances to get dogs of their choice. The findings revealed that no single attribute drove choice, indicating that people have complex preferences and these vary widely across individuals. Nonhuman animal shelters may be able to increase their adoption rates by providing more variety and not just dogs typically thought of as "in demand" but those who represent a range of diversity through the utilization of animal relocation programs. PMID- 25117183 TI - Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine. AB - BACKGROUND AND OBJECTIVE: Vandetanib is a selective inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) signalling, indicated for the treatment of medullary thyroid cancer. We investigated potential drug-drug interactions between vandetanib and metformin [organic cation transporter 2 (OCT2) substrate; NCT01551615]; digoxin [P-glycoprotein (P-gp) substrate; NCT01561781]; midazolam [cytochrome P450 (CYP) 3A4 substrate; NCT01544140]; omeprazole (proton pump inhibitor) or ranitidine (histamine H2-receptor antagonist; both NCT01539655). METHODS: Four open-label, phase I studies were conducted in healthy volunteers: n = 14 (metformin), n = 14 (digoxin), n = 17 (midazolam), n = 16 (omeprazole), n = 18 (ranitidine). Three of these comprised the following regimens: metformin 1000 mg +/- vandetanib 800 mg, midazolam 7.5 mg +/- vandetanib 800 mg, or digoxin 0.25 mg +/- vandetanib 300 mg. The randomized study comprised vandetanib 300 mg alone and then either (i) omeprazole 40 mg (days 1-4), and omeprazole + vandetanib (day 5); or (ii) ranitidine 150 mg (day 1), and ranitidine + vandetanib (day 2). The primary objective assessed metformin, digoxin, midazolam and vandetanib pharmacokinetics. RESULTS: Vandetanib + metformin increased metformin area under the plasma concentration time curve from zero to infinity (AUC0-infinity) and maximum observed plasma concentration (Cmax) by 74 and 50 %, respectively, and decreased the geometric mean metformin renal clearance (CLR) by 52 % versus metformin alone. Vandetanib + digoxin increased digoxin area under the concentration-time curve from zero to the last quantifiable concentration (AUC0-last) and Cmax by 23 and 29 %, respectively, versus digoxin alone, with only a 9 % decrease in CLR. Vandetanib had no effect on midazolam exposure. Vandetanib exposure was unchanged during co administration with omeprazole/ranitidine. Treatment combinations were generally well tolerated. CONCLUSION: Patients receiving vandetanib with metformin/digoxin may require additional monitoring of metformin/digoxin, with dose adjustments where necessary. Vandetanib with CYP3A4 substrates or omeprazole/ranitidine is unlikely to result in clinically relevant drug-drug interactions. PMID- 25117186 TI - Caesarean delivery: truths and consequences. PMID- 25117184 TI - Vancomycin pharmacokinetic and pharmacodynamic models for critically ill patients with post-sternotomy mediastinitis. AB - BACKGROUND AND OBJECTIVE: Vancomycin is commonly used to treat serious methicillin-resistant staphylococcal infections, especially post-sternotomy mediastinitis (PSM). However, information on pharmacokinetics and pharmacodynamics in intensive care unit (ICU) patients remains scarce. We conducted vancomycin pharmacokinetic-pharmacodynamic modeling for ICU patients with PSM. METHODS: This cohort study included 30 consecutive patients who received multiple vancomycin doses during primary closed drainage of PSM with Redon catheters, targeting serum drug trough concentrations of 25-35 mg/L, and generating 359 serum vancomycin concentration-time values for analysis. Population pharmacodynamics served to describe the withdrawal of Redon catheters, i.e., the probability of in-ICU cure. RESULTS: Vancomycin pharmacokinetics corresponded to a two-compartment open model with first-order elimination kinetics. Mean [between-subject variability] population estimates were 1.91 (men)/1.25 (women) [0.28] L/h for vancomycin elimination, with intercompartmental clearance of 5.71 [1.01] L/h, and respective central and peripheral distribution volumes of 21.9 and 68 [0.53] L. Vancomycin clearance increased with body weight and declined with severity at ICU admission and serum creatinine (SCr), thereby allowing the prediction of the vancomycin plateau. Intercompartmental clearance decreased with diabetes mellitus (-70 %). The probability of withdrawing all Redon catheters (patient cured) was dependent only on the area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) exposures ratio in plasma. Neither preoperative factors, antistaphylococcal co-treatments, nor the initial number of Redon catheters significantly influenced this probability. The AUC/MIC exposures ratio had no significant effect on SCr levels. CONCLUSION: These modeling analysis results identified five clinically relevant covariates that influenced vancomycin pharmacokinetics and might achieve better individualization of vancomycin dosing for methicillin-resistant staphylococcal PSM in ICU patients. PMID- 25117187 TI - The CROWN Initiative: journal editors invite researchers to develop core outcomes in women's health. PMID- 25117188 TI - Improving VBAC rates: the combined impact of two management strategies. AB - BACKGROUND: Caesarean section rates in Australia have risen to >30%, with repeat caesarean delivery the most common indication. One method of reducing caesarean delivery rates is to increase rates of vaginal birth after caesarean section (VBAC). AIMS: To determine the combined effect of two management strategies on the rates of successful VBAC in women experiencing their first pregnancy following primary caesarean section. METHODS: Prospective cohort study from May 2009 to October 2010 at a metropolitan Australian teaching hospital. The strategies studied were (i) allocating responsibility for VBAC candidates attempting labour to the hospital's three high-risk obstetric consultants and (ii) implementing a next birth after caesarean (NBAC) antenatal clinic designed to counsel and support women deciding on mode of birth for their next pregnancy after a primary caesarean section. Data were collected from Obstetrix, a NBAC logbook and medical records of 396 eligible women who gave birth during the study period. RESULTS: Overall VBAC rates improved from 17.2% in 2006 prior to implementation of the combined strategies, to 27.0% over the studied period (P < 0.001). Of those women who desired and attempted a VBAC, the success rate was 64.4%. Regression analysis identified an increased likelihood of attempted vaginal birth where malpresentation was the indication for previous caesarean, while Eastern Asian ethnicity was associated with increased likelihood of choosing repeat caesarean. CONCLUSIONS: A dedicated NBAC clinic and more consistent approach to labour management can help improve VBAC rates. Further targeted counselling towards women with previous malpresentation and/or East Asian descent may further improve VBAC attempt rates. PMID- 25117189 TI - Perineal outcome and the risk of pelvic floor dysfunction: a cohort study of primiparous women. AB - BACKGROUND: Pelvic floor dysfunction (PFD) is the most common complication of childbirth. Assumptions have been made that perineal trauma increases the risk of PFD compared to an intact perineum, however the evidence for this is lacking. The aim of this study was to explore the relationship between perineal outcome and postpartum PFD. MATERIALS AND METHODS: Prospective cohort study design, with a self-reported quality of life (QOL) questionnaire mailed to all primiparous women with a non-instrumental delivery at The Townsville Hospital between 2011 and 2012 (n = 766). ANOVA was used to compare how the symptoms of PFD affect QOL in women with an intact perineum, episiotomy or spontaneous tear. RESULTS: Seventy-nine percent of the population had perineal injury; 60% had a spontaneous tear and 19% had an episiotomy. Ninety-seven percent of women who completed the questionnaire (n = 196) complained of PFD symptoms. Women with episiotomy had the best QOL, reporting the lowest levels of urinary dysfunction (statistically significant). No differences between the groups were found for symptoms of bowel, prolapse or sexual dysfunction. CONCLUSIONS: This study shows a relationship between perineal outcome and PFD and suggests that an episiotomy is associated with the least morbidity due to symptoms of urinary incontinence. Additional large-scale prospective research is required to further investigate and delineate the impact of childbirth on PFD. PMID- 25117190 TI - Teetering near the edge; women's experiences of anal incontinence following obstetric anal sphincter injury: an interpretive phenomenological research study. AB - BACKGROUND: Obstetric anal sphincter injury (OASIS) following vaginal delivery increases the risk of anal incontinence (AI). Subsequent vaginal delivery and ageing increase the risk of worsening symptoms. Very little literature describes any in-depth understanding of what it is like to live with AI following a history of known OASIS. AIM: To describe and interpret women's experience of AI following OASIS and its impact on quality of life. METHODS: An interpretive phenomenological study was conducted in a level 2 tertiary hospital in South Australia. Women with a history of OASIS and AI were purposefully recruited. The St Marks Vaizey score was utilised to identify symptom severity. Semi-structured open-ended interviews were conducted, and data were analysed utilising Van Manen thematic analysis. RESULTS: Participants (n = 10) aged 26-56 years. All women were symptomatic of AI following OASIS, and 80% had received a primary OASIS at their first vaginal delivery. The St Marks Vaizey score mean was 9.1 (range within 4-22). Three essential themes grieving for loss, silence, striving for normality with eight subthemes identified a significant sense of loss and psychological impact of AI for this group of women. CONCLUSION: Health professionals require a greater understanding of the negative impact of OASIS and AI on women's quality of life. This may improve the management, education and clinical care of this condition which may result as a consequence of OASIS. PMID- 25117191 TI - Offering HPV vaccination to women treated for high-grade cervical intra epithelial neoplasia: what do you need to know? PMID- 25117192 TI - Caution regarding first trimester screening for pre-eclampsia. PMID- 25117193 TI - Re: New directions in the prediction of pre-eclampsia. PMID- 25117194 TI - Re: New directions in the prediction of pre-eclampsia. PMID- 25117195 TI - The Accuracy of Template-Guided Refill Technique of Intrathecal Pumps Controlled by Fluoroscopy: An Observational Study. AB - OBJECTIVES: Intrathecal drug therapy is being utilized increasingly for the treatment of chronic refractory pain. However, performing the regular pump refill procedures caries the potential risk of medication injection into the subcutaneous tissue. The aim of this study was to assess the accuracy of this template-guided refill technique by means of fluoroscopic evaluation. MATERIALS AND METHODS: In 23 patients, the difference between the identification of the reservoir fill port center using the manufacturer's template and fluoroscopic guidance was assessed on four consecutive refill procedures by a two physicians. A distance surpassing that between the center and the margin of the port (3.5 mm) was considered a clinically relevant deviation. Analyses were performed with a one-sample t-test, with p < 0.05 indicating statistical significance. RESULTS: The mean difference distance between identification markings of the target with fluoroscopic guidance and with the template was 8.2 mm, with limited variance (2.7 mm). For all individual refill procedures, the port center identification accuracy differed significantly from zero (all p < 0.001) and from the clinically relevant cut-off point of 3.5 mm (all p < 0.001). Only seven attempts (6.4%) were within the margins of the fill port. CONCLUSIONS: Our results suggest poor accuracy of insertion point identification using the template. This highlights the potential risk of errors related to identification of the puncture site using the template-guided technique. PMID- 25117196 TI - Ceftobiprole medocaril: a review of its use in patients with hospital- or community-acquired pneumonia. AB - Ceftobiprole, the active metabolite of the prodrug ceftobiprole medocaril (Zevtera((r))), is a new generation broad-spectrum intravenous cephalosporin with activity against methicillin-resistant Staphylococcus aureus. Ceftobiprole exhibits potent in vitro activity against a number of Gram-positive and Gram negative pathogens associated with hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP). It is the first cephalosporin monotherapy approved in the EU for the treatment of both HAP (excluding ventilator associated pneumonia [VAP]) and CAP. In phase III trials, ceftobiprole medocaril was noninferior, in terms of clinical cure rates at the test-of-cure visit, to ceftazidime plus linezolid in patients with HAP and to ceftriaxone +/- linezolid in patients with CAP severe enough to require hospitalization. In patients with HAP, noninferiority of ceftobiprole medocaril to ceftazidime plus linezolid was not demonstrated in a subset of patients with VAP. In patients with CAP, ceftobiprole medocaril was effective in those at risk for poor outcomes (pneumonia severity index >=91, Pneumonia Patient Outcomes Research Team score IV V or bacteraemic pneumonia). In the phase III trials, ceftobiprole medocaril was generally well tolerated, with ~10 % of patients discontinuing the treatment because of adverse events. The most common treatment-related adverse events occurring in ceftobiprole recipients in the trials in patients with HAP or CAP included nausea, diarrhoea, infusion site reactions, vomiting, hepatic enzyme elevations and hyponatraemia. Therefore, ceftobiprole medocaril monotherapy offers a simplified option for the initial empirical treatment of patients with HAP (excluding VAP) and in those with CAP requiring hospitalization. PMID- 25117197 TI - Daclatasvir + asunaprevir: first global approval. AB - The combination of daclatasvir + asunaprevir [Daklinza((r)) + Sunvepra((r)) (Japan)], two direct-acting antiviral agents, has been developed by Bristol-Myers Squibb for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 infections, including those with compensated cirrhosis. Daclatasvir + asunaprevir has received its first global approval in this indication in Japan. Daclatasvir + asunaprevir is the first all-oral, interferon- and ribavirin-free regimen for this indication. This article summarizes the milestones in the development of daclatasvir + asunaprevir leading to this first approval for the treatment of chronic HCV genotype 1 infections. PMID- 25117198 TI - Treatment of HCV infection with the novel NS3/4A protease inhibitors. AB - HCV NS3/4A serine protease inhibitors are the first class of direct acting antivirals (DAA) introduced in clinical practice. The first generation agents, selective against HCV genotype 1, are used in association with pegylated interferons and ribavirin allowing increased cure rates at the price of increased toxicity, significant drug interactions and high risk of selecting mutants conferring cross-resistance to the entire class. A large number of second-wave HCV protease inhibitors are currently in clinical development. Advancements include higher potency, activity against a wider number of genotypes, improved tolerability, easier dosing schedules, although their genetic barrier to resistance remains low, especially for subtype 1a, except for the most recent grazoprevir and ACH-2684. The most relevant progress regards the combination with other classes of DAA allowing construction of interferon-free regimens of short duration, good tolerability with exceptionally high cure rates. PMID- 25117200 TI - Cross-Cultural Considerations in Pediatric Neuropsychology: A Review and Call to Attention. AB - In the search to understand the basis of performance discrepancies, many clinicians are recognizing that, often, factors with no direct relationship to brain functioning influence performance on neuropsychological measures of cognition among children and adolescents. The emergent research on cross-cultural neuropsychology indicates that while the test performance discrepancies do indeed exist, they can be explained by a number of other factors, some of which are known and others that have yet to be operationalized or even identified. While a review of all such factors is beyond the scope of this article, an examination of those that have received the most attention is presented: factors associated with the examinee, factors associated with the neuropsychological measures, cultural competency of the examiner, and factors at the organizational/political level. PMID- 25117201 TI - Factors that predict remission of infant atopic dermatitis: a systematic review. AB - The individual prognosis of infants with atopic dermatitis (AD) is important for parents, healthcare professionals, and society. The aim of this study was to investigate predictors for remission of infant AD until school age. A systematic review was carried out of clinical and epidemiological studies investigating the effect of filaggrin gene (FLG) loss-of-function mutations, sex, exposure to pets, topical anti-inflammatory treatment, disease severity, and atopic sensitization during infancy on complete remission of infant-onset AD until 6-7 years of age. Systematic electronic searches until September 2013, data abstraction, and study quality assessment (Newcastle-Ottawa Scale) were performed. From 3,316 abstracts identified, 2 studies of good study quality were included. Parental allergies and sex did not significantly affect remission. For non-remission of AD, the included articles reported an association with any atopic sensitization at 2 years old (adjusted odds ratio [aOR] 2.76; 95% confidence interval (CI) 1.29-5.91), frequent scratching with early AD (aOR 5.86; 95% CI 3.04-11.29), objective severity score at 2 years old (aOR 1.10; 95% CI 1.07-1.14), and exposure to pets (cat OR 2.33; 95% CI 0.85-6.38). It is largely unknown which factors predict remission of infant AD. This is a highly relevant research gap that hinders patient information on the prognosis of infant-onset AD. PMID- 25117199 TI - Direct detection of biotinylated proteins by mass spectrometry. AB - Mass spectrometric strategies to identify protein subpopulations involved in specific biological functions rely on covalently tagging biotin to proteins using various chemical modification methods. The biotin tag is primarily used for enrichment of the targeted subpopulation for subsequent mass spectrometry (MS) analysis. A limitation of these strategies is that MS analysis does not easily discriminate unlabeled contaminants from the labeled protein subpopulation under study. To solve this problem, we developed a flexible method that only relies on direct MS detection of biotin-tagged proteins called "Direct Detection of Biotin containing Tags" (DiDBiT). Compared with conventional targeted proteomic strategies, DiDBiT improves direct detection of biotinylated proteins ~200 fold. We show that DiDBiT is applicable to several protein labeling protocols in cell culture and in vivo using cell permeable NHS-biotin and incorporation of the noncanonical amino acid, azidohomoalanine (AHA), into newly synthesized proteins, followed by click chemistry tagging with biotin. We demonstrate that DiDBiT improves the direct detection of biotin-tagged newly synthesized peptides more than 20-fold compared to conventional methods. With the increased sensitivity afforded by DiDBiT, we demonstrate the MS detection of newly synthesized proteins labeled in vivo in the rodent nervous system with unprecedented temporal resolution as short as 3 h. PMID- 25117204 TI - "Can we declare victory and move on?" The case against funding burden-of-disease studies. AB - Resources devoted to the development of burden-of-disease studies detract from much needed cost-effectiveness and cost-benefit studies. Practitioners need to help funders of burden-of-disease projects recognize the potential of all tools of decision analysis and economic evaluation in improving the efficiency and equity for the health care system. PMID- 25117203 TI - Identification of a putative Tdp1 inhibitor (CD00509) by in vitro and cell-based assays. AB - Mutations of DNA repair pathways contribute to tumorigenesis and provide a therapeutic target for synthetic lethal interactions in tumor cells. Given that tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs stalled topoisomerase-I DNA complexes, we hypothesized that inhibition of Tdp1 has synthetic lethal effects in some cancers. To test this, we screened tumor arrays for Tdp1 expression and observed that Tdp1 is expressed in many tumors, including more than 90% of human breast tumors. Subsequent chemical screening identified putative Tdp1 inhibitors. Treatment of control human mammary epithelial cells and the breast cancer cell line MCF-7 with compound CD00509 preferentially sensitized MCF-7 cells to camptothecin and decreased cell proliferation 25% more than camptothecin treatment alone. This suggests that CD00509 specifically targeted Tdp1 in vitro, and CD00509 increased the sensitivity of wild-type murine embryonic fibroblasts (MEFs) to camptothecin to a degree comparable to that of Tdp1(-/-) MEFs. In addition, consistent with poly ADP-ribose polymerase-1 (PARP-1) collaborating with Tdp1 in DNA repair, combined Tdp1 and PARP-1 inhibition was more detrimental to MCF-7 cells than either treatment alone, whereas the combination was not additively harmful to control mammary cells. We conclude that targeting Tdp1 in anticancer therapy preferentially enhances the sensitivity of some breast cancer cells to camptothecin and may be an effective adjuvant for breast cancer therapy. PMID- 25117205 TI - Hospital-based health technology assessment: insights from New Zealand. PMID- 25117206 TI - Neuropsychological Assessment of Children With Reading Disabilities From 8 to 10 Years Old: An Exploratory Portuguese Study. AB - Reading disabilities are one of the most significant causes of school failure and may result from different causes and cognitive processes. A comprehensive battery of neuropsychological tests was applied to a control group of 102 children (46 girls, 56 boys) with no history of learning disabilities and 32 children (13 girls, 19 boys) with poor reading achievement (PRA) to characterize their cognitive profile. A principal component analysis of the cognitive measures was undertaken to identify cognitive domains. Age-adjusted normative data were computed from controls for verbal and visuospatial abilities, psychomotor skills, executive functions, and a total score. Significant differences were found between the 2 groups. Although single tests could not identify children with PRA, measures of oral and written language, immediate and working memory, calculation, and verbal learning discriminated the 2 groups. A logistic regression model using these factors allowed us to identify 91.2% of healthy children and 96.9% of children with PRA. PRA may result from different patterns of cognitive difficulties, and it is more common in children with oral language and working memory deficits. Wide-range cognitive testing is necessary to identify strong and weak areas to plan personalized intervention programs. PMID- 25117208 TI - Effect of positive airway pressure therapy on seizure control in patients with epilepsy and obstructive sleep apnea. AB - Previous studies suggest that treatment for obstructive sleep apnea (OSA) in patients with epilepsy can improve seizure control. We investigated the effect of positive airway pressure (PAP) therapy on seizures in adults with epilepsy referred to the Cleveland Clinic for polysomnography (PSG) from 1997 to 2010. Seizure outcome at baseline and 1 year later was compared in patients with no OSA (apnea-hypopnea index [AHI] <5), patients with PAP-treated OSA, and patients with untreated OSA. One hundred thirty-two subjects (age: 40.2+/-13 (18-76) years, 65.4% female) were included. Seventy-six (57.6%) subjects had OSA; of these, 43 (56.6%) were on PAP therapy, and 33 (43.4%) were not on PAP therapy (either PAP intolerant or refused therapy). Of the group with PAP-treated OSA, 83.7% were adherent (use >=4 h/night at least 5 nights/week). The percentage of subjects with >=50% seizure reduction and the mean percentage of seizure reduction were significantly greater in the group with PAP-treated OSA (73.9%; 58.5%) than in subjects with untreated OSA (14.3%; 17.0%). There were significantly more subjects with successful outcomes (with >=50% seizure reduction or seizure-free at both baseline and follow-up) in the group with PAP-treated OSA (83.7%) than in the groups with no OSA (53.6%) and untreated OSA (39.4%). After adjusting for age, gender, body mass index, AHI, and epilepsy duration, we found that the odds of successful outcomes in subjects in the group with PAP-treated OSA were 9.9 and 3.91 times those of the groups with untreated OSA and no OSA, respectively. The group with PAP-treated OSA had 32.3 times the odds of having a >=50% seizure reduction compared with the group with untreated OSA and 6.13 times compared with the group with no OSA. Positive airway pressure therapy appears to produce beneficial effects on seizures in adult patients with epilepsy and OSA. PMID- 25117209 TI - Mycobacterium ulcerans disease (Buruli ulcer) in Mali: A new potential African endemic country. PMID- 25117207 TI - The neurosteroid 5beta-pregnan-3alpha-ol-20-one enhances actions of etomidate as a positive allosteric modulator of alpha1beta2gamma2L GABAA receptors. AB - BACKGROUND AND PURPOSE: Neurosteroids potentiate responses of the GABAA receptor to the endogenous agonist GABA. Here, we examined the ability of neurosteroids to potentiate responses to the allosteric activators etomidate, pentobarbital and propofol. EXPERIMENTAL APPROACH: Electrophysiological assays were conducted on rat alpha1beta2gamma2L GABAA receptors expressed in HEK 293 cells. The sedative activity of etomidate was studied in Xenopus tadpoles and mice. Effects of neurosteroids on etomidate-elicited inhibition of cortisol synthesis were determined in human adrenocortical cells. KEY RESULTS: The neurosteroid 5beta pregnan-3alpha-ol-20-one (3alpha5betaP) potentiated activation of GABAA receptors by GABA and allosteric activators. Co-application of 1 MUM 3alpha5betaP induced a leftward shift (almost 100-fold) of the whole-cell macroscopic concentration response relationship for gating by etomidate. Co-application of 100 nM 3alpha5betaP reduced the EC50 for potentiation by etomidate of currents elicited by 0.5 MUM GABA by about three-fold. In vivo, 3alpha5betaP (1mg kg(-1) ) reduced the dose of etomidate required to produce loss of righting in mice (ED50 ) by almost 10-fold. In tadpoles, the presence of 50 or 100 nM 3alpha5betaP shifted the EC50 for loss of righting about three- or ten-fold respectively. Exposure to 3alpha5betaP did not influence inhibition of cortisol synthesis by etomidate. CONCLUSIONS AND IMPLICATIONS: Potentiating neurosteroids act similarly on orthosterically and allosterically activated GABAA receptors. Co-application of neurosteroids with etomidate can significantly reduce dosage requirements for the anaesthetic, and is a potentially beneficial combination to reduce undesired side effects. PMID- 25117212 TI - Bacteria aerosol spread and wound bacteria reduction with different methods for wound debridement in an animal model. AB - Debridement is essential in wound treatment to remove necrotic tissue and wound bacteria but may lead to bacteria spread by aerosolization. This study investigated the wound bacterial reduction and bacterial transmission induced by debridement using curette, plasma-mediated bipolar radiofrequency ablation (Coblation(r)) or hydrodebridement (Versajet(r)). Full thickness dermal wounds in porcine joint specimens inoculated with S. aureus were debrided with curette, Coblation, Versajet, or were left untreated. During and after debridement, aerosolized bacteria were measured and to assess wound bacterial load, quantitative swab samples were taken from each wound. Only Coblation was able to reduce the bacterial load of the wound significantly. Versajet debridement resulted in a significant bacterial aerosolization, but this was not the case with Coblation and curette debridement. This study shows that Coblation is a promising wound debridement method, which effectively reduces the wound bed bacterial load without the risk of bacterial aerosolization. PMID- 25117216 TI - Spectrum of Mathematical Weaknesses: Related Neuropsychological Correlates. AB - Math disorders have been recognized for as long as language disorders yet have received far less research. Mathematics is a complex construct and its development may be dependent on multiple cognitive abilities. Several studies have shown that short-term memory, working memory, visuospatial skills, processing speed, and various language skills relate to and may facilitate math development and performance. The hypotheses explored in this research were that children who performed worse on math achievement than on Full-Scale IQ would exhibit weaknesses in executive functions, memory, and visuoperceptual skills. Participants included 436 children (27% girls, 73% boys; age range = 5-17 years, M(age) = 9.45 years) who were referred for neuropsychological evaluations due to academic and/or behavioral problems. This article specifically focuses on the spectrum of math weakness rather than clinical disability, which has yet to be investigated in the literature. Results suggest that children with relative weakness to impairments in math were significantly more likely to have cognitive weaknesses to impairments on neuropsychological variables, as compared with children without math weaknesses. Specifically, the math-weak children exhibit a weakness to impairment on measures involving attention, language, visuoperceptual skills, memory, reading, and spelling. Overall, our results suggest that math development is multifaceted. PMID- 25117210 TI - Left ventricular hypertrophy and obesity: only a matter of fat? AB - Obesity can be regarded as an energy balance disorder in which inappropriate expansion and dys-function of adipose tissue lead to unfavorable outcomes. Even in the absence of hypertension, adiposity induces structural and functional changes in the heart through hemodynamic and non hemodynamic factors. In the "obese" heart, besides the growth of cardiomyocytes, interstitial fat infiltration and triglyceride accumulation in the contractile elements importantly contribute to left-ventricular mass (LVM) accrual, hypertrophy (LVH) and geometric pattern. In harmony with this, the likelihood of LVH is greater in either obese normotensive or hypertensive individuals than in their non-obese counterparts. Interestingly, recent observations highlight the increasing prevalence of the "concentric" (ie, combined remodeling and hypertrophy), rather than "eccentric" pattern of LV geometry in obesity. Nonetheless, obesity is linked with lack of decrease, or even increase, of LVM over time, independently of blood pressure control and hypertensive treatment. Although obesity-related LV changes result in progressive systolic and diastolic heart failure, the assessment of LVM and LVH in obese individuals still remains a difficult task. In this scenario, it is tempting to speculate that therapeutic interventions for reversal of LVH in obesity should either overcome the "non-hemodynamic" factors or reduce the hemodynamic load. Indeed, weight loss, either achieved by lifestyle changes or bariatric procedures, decreases LVM and improves LV function regardless of blood pressure status. These and other mechanistic insights are discussed in this review, which focuses on "adipose dysfunction" as potential instigator of, and putative therapeutic target for, LVH regression in the setting of obesity. PMID- 25117217 TI - ELISPOT Techniques. AB - The enzyme-linked immunospot (ELISPOT) assay is a widely used method for enumerating antigen-specific cytokine-producing or antibody-secreting immune cells. It is one of the most effective immunological and diagnostic approaches to detect and quantify low-frequency cytokine- or antibody-producing cells in human and animal tissues, such as peripheral blood, lymph nodes, and spleen. Detection and quantification of specific cytokine-producing cells by the ELISPOT assay is based on the formation of visible spots at the site of cytokine release by the cells under investigation (e.g., T cells) using pairs of different capture and detection antibodies under optimized conditions.Here we focus mainly on practical, optimized protocols for cytokine ELISPOT assays for detection of mouse and human cytokine-producing immune cells (e.g., peripheral blood mononuclear cells, PBMC), including suggestions for trouble-shooting and optimizing steps for problematic tissue samples. PMID- 25117211 TI - Neuroprotective effects of the anti-cancer drug sunitinib in models of HIV neurotoxicity suggests potential for the treatment of neurodegenerative disorders. AB - BACKGROUND AND PURPOSE: Anti-retrovirals have improved and extended the life expectancy of patients with HIV. However, as this population ages, the prevalence of cognitive changes is increasing. Aberrant activation of kinases, such as receptor tyrosine kinases (RTKs) and cyclin-dependent kinase 5 (CDK5), play a role in the mechanisms of HIV neurotoxicity. Inhibitors of CDK5, such as roscovitine, have neuroprotective effects; however, CNS penetration is low. Interestingly, tyrosine kinase inhibitors (TKIs) display some CDK inhibitory activity and ability to cross the blood-brain barrier. EXPERIMENTAL APPROACH: We screened a small group of known TKIs for a candidate with additional CDK5 inhibitory activity and tested the efficacy of the candidate in in vitro and in vivo models of HIV-gp120 neurotoxicity. KEY RESULTS: Among 12 different compounds, sunitinib inhibited CDK5 with an IC50 of 4.2 MUM. In silico analysis revealed that, similarly to roscovitine, sunitinib fitted 6 of 10 features of the CDK5 pharmacophore. In a cell-based model, sunitinib reduced CDK5 phosphorylation (pCDK5), calpain-dependent p35/p25 conversion and protected neuronal cells from the toxic effects of gp120. In glial fibrillary acidic protein-gp120 transgenic (tg) mice, sunitinib reduced levels of pCDK5, p35/p25 and phosphorylated tau protein, along with amelioration of the neurodegenerative pathology. CONCLUSIONS AND IMPLICATIONS: Compounds such as sunitinib with dual kinase inhibitory activity could ameliorate the cognitive impairment associated with chronic HIV infection of the CNS. Moreover, repositioning existing low MW compounds holds promise for the treatment of patients with neurodegenerative disorders. PMID- 25117219 TI - A comparison of the degree of effort involved in the TOMM and the ACS Word Choice Test using a dual-task paradigm. AB - The aims of the current study were to: (a) examine the predictive validity and efficacy of the Advanced Clinical Solutions Word Choice Test (WCT) as a measure of effort relative to the Test of Memory Malingering (TOMM); (b) investigate whether performing a dual (distraction) task would undermine performance on either test; (c) assess the effect of coaching on the diagnostic accuracy of both the WCT and the TOMM; and (d) establish an optimal cut score for the WCT. The current study used a simulation design based on an analogue design in which normal participants were instructed to either apply full effort or simulate a brain injury on the tasks without being detected. Participants included 93 undergraduate university students who were randomly assigned to 1 of 4 conditions: (a) distraction, (b) uncoached traumatic brain injury (TBI) simulators, (c) coached TBI simulators, or (d) full effort. The results demonstrated that the WCT and the TOMM were effective in detecting simulated cognitive impairment. Both tests were resistant to the effects of distraction and were equally effective in detecting coached and uncoached simulators. A cut score of 42 on the WCT was found to provide optimal specificity and sensitivity on the test. PMID- 25117220 TI - History of plant lectin research. AB - Numerous plant species are known to express one or more lectins or proteins containing a lectin domain, enabling these proteins to select and bind specific carbohydrate structures. The group of plant lectins is quite heterogeneous since lectins differ in their molecular structure, specificity for certain carbohydrate structures, and biological activities resulting therefrom. This chapter presents a short historical overview on how plant lectin research has evolved over the years from a discipline aiming merely at the purification and characterization of plant lectins towards the application of plant lectins as tools in glycobiology. PMID- 25117221 TI - Fungal lectins: a growing family. AB - Fungi are members of a large group of eukaryotic organisms that include yeasts and molds, as well as the most familiar member, mushrooms. Fungal lectins with unique specificity and structures have been discovered. In general, fungal lectins are classified into specific families based on their amino acid sequences and three-dimensional structures. In this chapter, we provide an overview of the approximately 80 types of mushroom and fungal lectins that have been isolated and studied to date. In particular, we have focused on ten fungal lectins (Agaricus bisporus, Agrocybe cylindracea, Aleuria aurantia, Aspergillus oryzae, Clitocybe nebularis, Marasmius oreades, Psathyrella velutina, Rhizopus stolonifer, Pholiota squarrosa, Polyporus squamosus), many of which are commercially available and their properties, sugar-binding specificities, structural grouping into families, and applications for biological research being described. The sialic acid specific lectins (Agrocybe cylindracea and Polyporus squamosus) and fucose specific lectins (Aleuria aurantia, Aspergillus oryzae, Rhizopus stolonifer, and Pholiota squarrosa) each showed potential for use in identifying sialic acid glycoconjugates and fucose glycoconjugates. Although not much is currently known about fungal lectins compared to animal and plant lectins, the knowledge accumulated thus far shows great promise for several applications in the fields of taxonomy, biomedicine, and molecular and cellular biology. PMID- 25117223 TI - Hemagglutination (inhibition) assay. AB - The hemagglutination assay is a simple and easy method to obtain semi quantitative data on the sugar binding and specificity of a lectin. An active lectin agglutinates erythrocytes by recognizing a carbohydrate on the cell surface and forming a cross-linked network in suspension. By serially diluting the lectin in a 96-well microtiter plate and adding a constant quantity of erythrocytes, the lectin activity can be estimated. PMID- 25117218 TI - IL-1beta and IL-18: inflammatory markers or mediators of hypertension? AB - Chronic inflammation in the kidneys and vascular wall is a major contributor to hypertension. However, the stimuli and cellular mechanisms responsible for such inflammatory responses remain poorly defined. Inflammasomes are crucial initiators of sterile inflammation in other diseases such as rheumatoid arthritis and gout. These pattern recognition receptors detect host-derived danger associated molecular patterns (DAMPs), such as microcrystals and reactive oxygen species, and respond by inducing activation of caspase-1. Caspase-1 then processes the cytokines pro-IL-1beta and pro-IL-18 into their active forms thus triggering inflammation. While IL-1beta and IL-18 are known to be elevated in hypertensive patients, no studies have examined whether this occurs downstream of inflammasome activation or whether inhibition of inflammasome and/or IL-1beta/IL 18 signalling prevents hypertension. In this review, we will discuss some known actions of IL-1beta and IL-18 on leukocyte and vessel wall function that could potentially underlie a prohypertensive role for these cytokines. We will describe the major classes of inflammasome-activating DAMPs and present evidence that at least some of these are elevated in the setting of hypertension. Finally, we will provide information on drugs that are currently used to inhibit inflammasome/IL 1beta/IL-18 signalling and how these might ultimately be used as therapeutic agents for the clinical management of hypertension. PMID- 25117222 TI - The "white kidney bean incident" in Japan. AB - Lectin poisoning occurred in Japan in 2006 after a TV broadcast that introduced a new diet of eating staple foods with powdered toasted white kidney beans, seeds of Phaseolus vulgaris. Although the method is based on the action of a heat stable alpha-amylase inhibitor in the beans, phaseolamin, more than 1,000 viewers who tried the method suffered from acute intestinal symptoms and 100 people were hospitalized. Lectins in the white kidney beans were suspected to be the cause of the trouble. We were asked to investigate the lectin activity remaining in the beans after the heat treatment recommended on the TV program. The test suggested that the heat treatment was insufficient to inactivate the lectin activity, which, combined with our ignorance of carbohydrate signaling in the intestine, was the cause of the problem. PMID- 25117224 TI - Preparation of affinity adsorbents and purification of lectins from natural sources. AB - Lectins are purified by affinity chromatography to take advantage of their carbohydrate-specific interactions. Highly efficient affinity adsorbents are powerful tools to obtain homogeneous lectins with distinct specificities. Here, we describe three methods to prepare affinity adsorbents by immobilizing carbohydrates or glycoconjugates on agarose gel beads. Because the ligands are immobilized via a stable and nonionic linkage under mild conditions, the adsorbents possess high binding capacity for lectins with low nonspecific adsorption and can withstand repeated use. The procedures require neither specialized techniques and apparatus nor highly toxic compounds. Using these adsorbents, many plant and animal lectins can be purified in a few steps. PMID- 25117225 TI - High-performance lectin affinity chromatography. AB - Lectin high-performance liquid chromatography techniques have contributed to the growing interest in glycoproteomics. Affinity chromatography is a very effective method to separate and purify trace amount of biological substances. In this chapter, we describe a basic procedure for separation of glycoproteins using commercially available lectin-HPLC columns. As an example, alpha-fetoprotein, known as a biomarker of liver cancer, can be separated at the level of their glyco-isomers by using a Lens culinaris agglutinin (LCA) column. PMID- 25117226 TI - Determination of glycan motifs using serial lectin affinity chromatography. AB - Serial lectin affinity chromatography is a convenient technique for characterizing glycan motifs (terminal glycan structures) of glycoproteins or released glycans. When these glycoconjugates are applied serially or in parallel to lectin-immobilized columns, information regarding the glycan motifs can be obtained. We demonstrate lectin affinity chromatographic methods for determining O-linked glycan structures of MUC1 purified from a breast cancer cell line, YMB S, N-linked glycan structures of serum prostate-specific antigen from prostate cancer, and serum alkaline phosphatases from choriocarcinoma. These lectin fractionated samples are analyzed quantitatively by measuring radioactivity, antigen contents are analyzed using enzyme-linked immunosorbent assay, and enzymatic activities are assessed. PMID- 25117227 TI - Lectin-probed western blot analysis. AB - Lectin-probed western blot analysis, the so-called lectin blot analysis, is a useful method to yield basic information on the glycan structures of glycoproteins, based on the carbohydrate-binding specificities of lectins. By lectin blot analysis, researchers can directly analyze the glycan structures without releasing the glycans from glycoproteins. Here, the author describes protocols for standard analysis, and applies analysis in combination with glycosidase digestion of blot. PMID- 25117228 TI - Solid-phase assay of lectin activity using HRP-conjugated glycoproteins. AB - Various enzyme-conjugated probes have been widely used for detection of specific interactions between biomolecules. In the case of glycan-protein interaction, horseradish peroxidase (HRP)-conjugated glycoproteins (HRP-GPs) are useful for the detection of carbohydrate-binding activity of plant and animal lectins. In this chapter, a typical solid-phase assay of the carbohydrate-binding activity of Sophora japonica agglutinin I, a Gal/GalNAc-specific lectin, using HRP-conjugated asialofetuin is described. HRP-GPs are versatile tools for probing lectin activities in crude extracts, screening many samples at one time, and applicable not only for solid-phase binding assays but also samples which are dot- or Western-blotted onto the membrane. PMID- 25117229 TI - A simple viral neuraminidase-based detection for high-throughput screening of viral hemagglutinin-host receptor specificity. AB - The correlation between precise interactions of influenza A virus hemagglutinins with host cell surface glycans having terminal sialic acids and host range specificity has provoked the development of a high-throughput viral-receptor specificity assay. Here, we describe the use of the virus itself as a specific antibody coupled to enzymes (virus with neuraminidase spikes) for determining its binding specificity to glycans, a strategy that reduces not only the cost but also the tedious steps of adding primary and secondary antibodies and washing between each step. All of the steps, including coating the glycopolymers onto microtiter plates, virus binding, and visual and quantitative detection of fluorescence products that correlate well with the amount of glycan-bound viruses, can be done within 3 h. This simple, rapid, sensitive, and reliable strategy is an ideal method for detection of high-throughput influenza virus receptor-binding preference not only for studies on viral evolution and transmission but also for viral surveillance in pandemic preparedness, leading to efficient prevention and control of the disease. PMID- 25117230 TI - Lectin affinity electrophoresis. AB - An interaction or a binding event typically changes the electrophoretic properties of a molecule. Affinity electrophoresis methods detect changes in the electrophoretic pattern of molecules (mainly macromolecules) that occur as a result of biospecific interactions or complex formation. Lectin affinity electrophoresis is a very effective method for the detection and analysis of trace amounts of glycobiological substances. It is particularly useful for isolating and separating the glycoisomers of target molecules. Here, we describe a sensitive technique for the detection of glycoproteins separated by agarose gel lectin affinity electrophoresis that uses antibody-affinity blotting. The technique is tested using alpha-fetoprotein with lectin (Lens culinaris agglutinin and Phaseolus vulgaris agglutinin)-agarose gels. PMID- 25117231 TI - Capillary-based lectin affinity electrophoresis for interaction analysis between lectins and glycans. AB - Capillary affinity electrophoresis (CAE) is a powerful technique for glycan analysis, and one of the analytical approaches for analyzing the interaction between lectins and glycans. The method is based on the high-resolution separation of fluorescently labeled glycans by capillary electrophoresis (CE) with laser-induced fluorescence detection (LIF) in the presence of lectins (or glycan binding proteins). CAE allows simultaneous determination of glycan structures in a complex mixture of glycans. In addition, we can calculate the binding kinetics on a specific glycan in the complex mixture of glycans with a lectin. Here, we show detailed procedures for capillary affinity electrophoresis of fluorescently labeled glycans with lectins using CE-LIF apparatus. Its application to screening a sialic acid binding protein in plant barks is also shown. PMID- 25117232 TI - Basic procedures for lectin flow cytometry. AB - Glycans located on the cell surface regulate cell-cell interaction, cell homing, and signal transmission, which are particularly important for communication among cells. Certain cell types contain unique cell surface glycan structures, which have been utilized as markers for characterization. Flow cytometry is a powerful technology that enables the examination of multiple parameters of individual cells (e.g., cell size, internal complexity, and surface marker expression level). In this chapter, we describe a step-by-step procedure on how to detect glycans on the cell surface of live cells by flow cytometer, using lectins. PMID- 25117233 TI - Histochemical staining using lectin probes. AB - In histochemistry and cytochemistry, lectins are often used as probes for the localization of carbohydrates in cells and tissues. With lectins, cells and tissues can be identified as a particular type or a group in situ. Various lectins have been used for mapping of normal cells and tissues, pathological diagnosis such as malignant transformation, and identification of cell lineages during development. This chapter describes light and electron microscopic methods using lectin probes for determining carbohydrate localization in cells and tissues. PMID- 25117234 TI - Equilibrium dialysis using chromophoric sugar derivatives. AB - Equilibrium dialysis has been used to examine the binding affinity of ligands to proteins. It is a simple and reliable method, which requires only inexpensive equipment. For analysis of lectin-sugar interactions, the lectin and sugar are placed in the individual chambers separated by the membrane to allow the sugar to diffuse into the lectin chamber. After equilibrium has been reached, the concentrations of the sugar in both chambers are determined to evaluate the sugar binding affinity of lectin. In this chapter, an example of the equilibrium dialysis experiment using the chromophoric derivatives of galactose and N acetylgalactosamine is demonstrated, which reveals the difference in the affinity as well as specificities of two different carbohydrate-binding sites present in the B-chains of the plant lectin ricin. PMID- 25117235 TI - Centrifugal ultrafiltration-HPLC method for interaction analysis between lectins and sugars. AB - The centrifugal ultrafiltration-HPLC method is a simple and rapid method for analyzing the binding interaction between lectins and sugars (oligosaccharides). In this method, a lectin is mixed with a fluorescent-labeled oligosaccharide in buffer and the unbound oligosaccharide recovered by centrifugal ultrafiltration is isolated and quantified by high-performance liquid chromatography. The binding activity is defined as a ratio (percentage) of the amount of bound oligosaccharide to that added, where the former is obtained by subtracting the amount of unbound oligosaccharide from the latter. The oligosaccharide-binding specificity of a lectin can be determined by comparing the binding activities with a variety of fluorescent-labeled oligosaccharides. The association constant and the optimum pH and temperature of the binding interaction between lectins and fluorescent-labeled oligosaccharides can be easily analyzed by this method. PMID- 25117236 TI - Surface plasmon resonance as a tool to characterize lectin-carbohydrate interactions. AB - Biosensors based on surface plasmon resonance (SPR) monitor changes in refractive index in the vicinity of a surface in a real-time manner, which allows rapid, label-free characterization of the interactions of various types of molecules, from quantitative measurements of binding kinetics, thermodynamics, and concentrations in complex samples to epitope analysis. This method is usually capable of analyzing affinities in the range of millimolar to picomolar and is sensitive (typically, the concentration range of the analyte is 0.1-100*Kd and the typical volumes needed are in the range of 50-150 MUL). There are two major applications of SPR biosensors for the analysis of lectin-carbohydrate interactions: detailed characterization of the interaction (e.g., specificity, affinity, kinetics, stoichiometry) and screening of lectin and carbohydrate/glycoconjugate interactions for diagnosis, identification of endogenous ligands, or binding properties of interest. Care should be taken, since the interaction of lectin and carbohydrate on the solid phase is complicated by the nonhomogeneous conditions under which binding occurs. However, this may in fact mimic some biological conditions, such as those occurring in cell-cell interactions. PMID- 25117237 TI - Isothermal calorimetric analysis of lectin-sugar interaction. AB - Isothermal titration calorimetry (ITC) is a powerful tool for analyzing lectin glycan interactions because it can measure the binding affinity and thermodynamic properties such as ?H and DeltaS in a single experiment without any chemical modification or immobilization. Here we describe a method for preparing glycan and lectin solution to minimize the buffer mismatch, setting parameters, and performing experiments. PMID- 25117238 TI - Carbohydrate-lectin interaction assay by fluorescence correlation spectroscopy using fluorescence-labeled glycosylasparagines. AB - Fluorescence correlation spectroscopy (FCS) is a high-throughput system for the assay of interactions in solution and can be used to measure the numbers of molecules and molecular size in micro-regions. FCS can be used to measure interactions in environments that are close to those in vivo. It is a useful technique for measuring bioactive substances, screening inhibitors, and detecting the binding of materials, as well as for determining K d and IC50 values. Glycosyl amino acids with natural oligosaccharides are useful for the interaction assay of oligosaccharides. Fluorescence probes can be introduced into the glycosyl amino acid while the whole structure of the oligosaccharide is maintained. Carbohydrate-lectin interaction in a solution assay system can be analyzed easily by FCS using fluorescence-labeled glycosylasparagine. PMID- 25117239 TI - Lectin-based glycomics: how and when was the technology born? AB - Lectin-based glycomics is an emerging, comprehensive technology in the post genome sciences. The technique utilizes a panel of lectins, which is a group of biomolecules capable of deciphering "glycocodes," with a novel platform represented by a lectin microarray. The method enables multiple glycan-lectin interaction analyses to be made so that differential glycan profiling can be performed in a rapid and sensitive manner. This approach is in clear contrast to another advanced technology, mass spectrometry, which requires prior glycan liberation. Although the lectin microarray cannot provide definitive structures of carbohydrates and their attachment sites, it gives useful clues concerning the characteristic features of glycoconjugates. These include differences not only in terminal modifications (e.g., sialic acid (Sia) linkage, types of fucosylation) but also in higher ordered structures in terms of glycan density, depth, and direction composed for both N- and O-glycans. However, before this technique began to be implemented in earnest, many other low-throughput methods were utilized in the late twentieth century. In this chapter, the author describes how the current lectin microarray technique has developed based on his personal experience. PMID- 25117240 TI - Frontal affinity chromatography (FAC): theory and basic aspects. AB - Frontal affinity chromatography (FAC) is a versatile analytical tool for determining specific interactions between biomolecules and is particularly useful in the field of glycobiology. This article presents its basic aspects, merits, and theory. PMID- 25117241 TI - Frontal affinity chromatography: practice of weak interaction analysis between lectins and fluorescently labeled oligosaccharides. AB - Frontal affinity chromatography (FAC) is a simple and effective method that is applicable to the analysis of interactions between glycans and glycan-recognition proteins, including lectins, with weak affinity ranging from 10(-4) to 10(-6) (M) in terms of dissociation constant (Kd). Using conventional instruments, such as a high-performance liquid chromatography (HPLC) system equipped with pump, injector, (fluorescent) detector, and data recorder, the dissociation constants for weak glycan-based interactions can be easily determined with high throughput and accuracy. Notably, if the glycans are labeled with fluorescent dyes, only a small amount of glycans is required for the analysis. Fluorescent labeling of glycans is a common technique, and an increasing number of fluorescent-labeled glycans are commercially available. In this chapter, an advanced FAC method using fluorescent-labeled glycans is described. PMID- 25117242 TI - Differential glycan analysis of an endogenous glycoprotein: toward clinical implementation--from sample pretreatment to data standardization. AB - There are huge numbers of clinical specimens being stored that contain potential diagnostic marker molecules buried by the coexistence of high-abundance proteins. To utilize such valuable stocks efficiently, we must develop appropriate techniques to verify the molecules. Glycoproteins with disease-related glycosylation changes are a group of useful molecules that have long been recognized, but their application is not fully implemented. The technology for comparative analysis of such glycoproteins in biological specimens has tended to be left behind, which often leads to loss of useful information without it being recognized. In this chapter, we feature antibody-assisted lectin profiling employing antibody-overlay lectin microarray, the most suitable technology for comparative glycoanalysis of a trace amount of glycoproteins contained in biological specimens. We believe that sharing this detailed protocol will accelerate the glycoproteomics-based discovery of glyco-biomarkers that has attracted recent attention; simultaneously, it will increase the value of clinical specimens as a gold mine of information that has yet to be exploited. PMID- 25117243 TI - Lectin-microarray technique for glycomic profiling of fungal cell surfaces. AB - Lectin microarrays are rows of lectins with different carbohydrate-binding specificities spotted on surfaces of glass slides. Lectin microarray technique enables glycomic analyses of carbohydrate composition of fungal cell walls. We will describe an application of the technique in analyzing cell surface glycome of yeast-form fungal cells in the living state. The analysis reveals genus- and species-dependent complex cell surface carbohydrate structures of fungi, and enabled us, therefore, to suggest that cell walls of yeast cells, which have been considered to have relatively simple structures, actually have a more complex structure containing galactose and fucose. This shows that the technique can be used to find new insights into the study of phylogenetic relations and into the classification of cells in the fungal kingdom based on cell wall glycome. PMID- 25117244 TI - Application of lectin microarray to bacteria including Lactobacillus casei/paracasei strains. AB - Since 2005, lectin microarray technology has emerged as a simple and powerful technique for comprehensive glycan analysis. By using evanescent-field fluorescence detection technique, it has been applied for analysis of not only glycoproteins and glycolipids secreted by eukaryotic cells but also glycoconjugates on the cell surface of live eukaryotic cells. Bacterial cells are known to be decorated with polysaccharides, teichoic acids, and proteins in the peptide glycans of their cell wall and lipoteichoic acids in their phospholipid bilayer. Specific glycan structures are characteristic of many highly pathogenic bacteria, while polysaccharides moiety of lactic acid bacteria are known to play a role as probiotics to modulate the host immune response. However, the method of analysis and knowledge of glycosylation structure of bacteria are limited. Here, we describe the development of a simple and sensitive method based on lectin microarray technology for direct analysis of intact bacterial cell surface glycomes. The method involves labeling bacterial cells with SYTOX Orange before incubation with the lectin microarray. After washing, bound cells are directly detected using an evanescent-field fluorescence scanner in a liquid phase. The entire procedure takes 3 h from putting labeled bacteria on the microarray to profiling its lectin binding affinity. Using this method, we compared the cell surface glycomes from 16 different strains of L. casei/paracasei. The lectin binding profile of most strains was found to be unique. Our technique provides a novel strategy for rapid profiling of bacteria and enables us to differentiate numerous bacterial strains with relevance to the biological functions of surface glycosylation. PMID- 25117245 TI - Live-cell imaging of human pluripotent stem cells by a novel lectin probe rBC2LCN. AB - We performed comprehensive glycome analysis of a large set of human pluripotent stem cells (hPSCs) using a high-density lectin microarray. We found that a recombinant lectin, rBC2LCN, binds exclusively to all of the undifferentiated hPSCs tested, but not to differentiated somatic cells. rBC2LCN can be used for both the staining and sorting of fixed and live hPSCs. rBC2LCN could serve as a novel detection reagent for hPSCs, particularly given that rBC2LCN is cost effective and, unlike conventional antibodies which require mammalian cells for their production, is easy to produce in a large amount (0.1 g/L) in an Escherichia coli expression system. Here we describe protocols for the fluorescence staining of fixed and live hPSCs and their detection by flow cytometry. PMID- 25117246 TI - Carbohydrate-binding specificity of lectins using multiplexed glyco-bead array. AB - Multiplexed bead array is an application that allows us to quantify multiple ligands simultaneously by using flow cytometry. Glycopeptides are immobilized on multiplexed beads, and the glycan-binding specificities of several lectins are determined. This strategy is easy, rapid, and suitable for small amount of samples, and allows the reliable elucidation under the identical condition. Such a technology is useful for analyzing characteristics and functions of lectins. PMID- 25117247 TI - Supported molecular matrix electrophoresis: a new membrane electrophoresis for characterizing glycoproteins. AB - Protein blotting is often used for identification and characterization of proteins on a membrane to which proteins separated by gel electrophoresis are transferred. The transferring process is sometimes problematic, in particular, for mucins and proteoglycans. Here, we describe a novel membrane electrophoresis technique, termed supported molecular matrix electrophoresis (SMME), in which a porous polyvinylidene difluoride (PVDF) membrane filter is used as the separation support. Proteins separated by this method can be immunoblotted without any transferring procedures. PMID- 25117248 TI - Overall strategy for functional analysis of animal lectins. AB - Animal lectins elicit biological functions through the interaction with glycan ligands. To clarify the functions of the lectins, both identification of their glycan ligand structure and assessment of impact of lectin-glycan interaction on the biological event are essential strategies. This chapter focuses on two of key useful methodologies for planning experiments based on the strategies. One is the detection of lectin-glycan interaction by the multivalent display of lectins and glycans. This methodology is a powerful means for identification of the glycan ligand structure and proteins and/or lipids carrying the glycan ligands for lectins. The other is the intervention of lectin-glycan interaction to assess the biological roles of lectins. Bioinformatics especially useful for animal lectins will be also described in this chapter. The concepts described in this chapter are versatile and applicable to a wide range of animal lectin research. PMID- 25117249 TI - Evaluation of glycan-binding specificity by glycoconjugate microarray with an evanescent-field fluorescence detection system. AB - The glycan microarray is now an essential tool used to study lectins. With this technique, glycan-binding specificity can be easily assessed by incubation with an array immobilizing a series of glycans. Glycan microarrays have been developed by numerous research groups around the world. Among the available microarrays, our glycan microarray has two unique characteristics: one is the incorporation of an evanescent-field fluorescence detection system and the other is the use of multivalent glycopolymers. These two unique properties allow the highly sensitive detection of only nanogram quantities of lectins even in crude samples such as cell lysates and cell culture media. Thus, this system is suitable for the initial screening of lectins, lectin-like molecules, lectin candidates, and lectin mutants. Here I describe the protocols employed to analyze the glycan binding specificity of lectins using our glycan microarray system. PMID- 25117250 TI - Potential usage for in vivo lectin screening in live animals utilizing cell surface mimetic glyco-nanoparticles, phosphorylcholine-coated quantum dots (PC QDs). AB - Utilizing glycosylated derivatives as a tag, we are able to explore novel counter receptor of endogenous lectins or lectin-like molecules in vivo. We have established the standardized methodology including preparation of glycosylated derivatives and construction of a platform for tracing the molecules in vivo at first. Combined use of an aminooxy-terminated thiol derivative and a phosphorylcholine (PC) derivative provides quantum dots (QDs) with novel functions for the chemical ligation of ketone-functionalized compounds and the prevention of nonspecific protein adsorption concurrently. In order to track the derivatives in vivo, near-infrared (NIR) fluorescence imaging of QDs displaying various simple sugars (glyco-PC-QDs) after administration into the tail vein of the mouse can be performed. It has revealed that distinct long-term delocalization over 2 h can be observed depending on the species of glycans ligated to PC-QDs at least in the liver. Until today we have performed live animal imaging utilizing various kinds of sialyl glyco-PC-QDs. They are still retained stably in whole body after 2 h while they showed significantly different in vivo dynamics in the tissue distribution, suggesting that structure/sequence of the neighboring sugar residues in the individual sialyl oligosaccharides might influence the final organ-specific distribution, which should be equivalent to the distribution of sialic acid-recognizing lectins. Here we describe a standardized protocol using ligand-displayed PC-QDs for live cell/animal imaging by versatile NIR fluorescence photometry without influence of size-dependent accumulation/excretion pathway for nanoparticles (e.g., viruses)>10 nm in hydrodynamic diameter by the liver. PMID- 25117251 TI - Remodeling cell surface glycans using glycosylation inhibitors. AB - Cell surface glycan remodeling is a useful method to modulate glycan-lectin interactions. In this chapter, a facile and reliable method to remodel mammalian cell surface N-glycans using inhibitors for N-glycan-processing enzymes is described. The method is widely applicable to many mammalian systems because those inhibitors work for the conserved glycosylation pathways among species. PMID- 25117252 TI - Remodeling of glycans using glycosyltransferase genes. AB - Remodeling of glycans on the cell surface is an essential technique to analyze cellular function of lectin-glycan ligand interaction. Here we describe the methods to identify the responsible enzyme (glycosyltransferase) regulating the expression of the glycan of interest and to modulate the glycan expression by overexpressing the glycosyltransferase gene. For the identification of the responsible enzyme, we introduce a new method, CIRES (correlation index-based responsible-enzyme gene screening), that consists of statistical comparison of glycan expression profile obtained by flow cytometry and gene expression profile obtained by DNA microarray. PMID- 25117253 TI - Functional assay using lectin gene targeting technologies (over-expression). AB - Function of lectin depends on its amino acid sequence of carbohydrate-recognition domain (CRD), conformation, and extracellular/intracellular localization. Altering lectin gene expression by over-expression or knockdown is a powerful tool for analyzing its cellular function. Here, we describe a method of lectin gene over-expression, taking a C-type lectin, mannan-binding protein (MBP), as an example. Carbohydrate-binding ability of MBP, its subcellular localization, and functional co-localization with ligand glycoprotein are assayed comparing with an inactive mutant MBP. PMID- 25117254 TI - Analysis of L-selectin-mediated cellular interactions under flow conditions. AB - Lymphocyte homing is mediated by a specific interaction between L-selectin expressed on lymphocytes and its ligands expressed on high endothelial venules (HEVs) in lymph nodes under physiological flow conditions. In this chapter, two methods for detecting L-selectin-mediated cellular interactions under shear stress mimicking physiological flow conditions are described. First, a modified Stamper-Woodruff cell-binding assay using leukocytes labeled with a fluorescent orange dye, CMTMR, is introduced. In this method, leukocytes are allowed to bind to frozen lymph node sections under shear stress and their binding to HEVs can be clearly visualized by fluorescence microscopy. Second, a parallel flow chamber assay is described. In this assay, leukocytes are allowed to roll on L-selectin ligand-expressing cells under various levels of shear stress and their adhesive interactions are recorded by a video camera equipped with an inverted microscope. These methods can be applied to determine the effects of various agents that might affect L-selectin-mediated lymphocyte homing and recruitment. PMID- 25117255 TI - Assessment of weak sugar-binding ability using lectin tetramer and membrane-based glycans. AB - To consider biological significance of glycosylation of proteins, it is necessary to evaluate the importance of sugar-recognition processes mediated by lectins. Though the interaction between sugars and proteins, especially animal lectins, is quite weak with K d approximately 10(-4) M, cellular and molecular recognitions mediated via sugar-protein interaction increase their avidity by 1-3 orders of magnitude by the self-association of both receptors and their ligands on cell surfaces. To assess the weak interaction between lectins and their sugar ligands, we established lectin tetramer binding to cell surface glycans using flow cytometry. This strategy is highly sensitive, and useful to determine whether or not a putative lectin domain may have sugar-binding ability. PMID- 25117256 TI - Perspectives in glycomics and lectin engineering. AB - This chapter would like to provide a short survey of the most promising concepts applied recently in analysis of glycoproteins based on lectins. The first part describes the most exciting analytical approaches used in the field of glycoprofiling based on integration of nanoparticles, nanowires, nanotubes, or nanochannels or using novel transducing platforms allowing to detect very low levels of glycoproteins in a label-free mode of operation. The second part describes application of recombinant lectins containing several tags applied for oriented and ordered immobilization of lectins. Besides already established concepts of glycoprofiling several novel aspects, which we think will be taken into account for future, more robust glycan analysis, are described including modified lectins, peptide lectin aptamers, and DNA aptamers with lectin-like specificity introduced by modified nucleotides. The last part of the chapter describes a novel concept of a glycocodon, which can lead to a better understanding of glycan-lectin interaction and for design of novel lectins with unknown specificities and/or better affinities toward glycan target or for rational design of peptide lectin aptamers or DNA aptamers. PMID- 25117257 TI - Molecular basis of a pandemic of avian-type influenza virus. AB - Despite heroic efforts to prevent the emergence of an influenza pandemic, avian influenza A virus has prevailed by crossing the species barriers to infect humans worldwide, occasionally with morbidity and mortality at unprecedented levels, and the virus later usually continues circulation in humans as a seasonal influenza virus, resulting in health-social-economic problems each year. Here, we review current knowledge of influenza viruses, their life cycle, interspecies transmission, and past pandemics and discuss the molecular basis of pandemic acquisition, notably of hemagglutinin (lectin) acting as a key contributor to change in host specificity in viral infection. PMID- 25117258 TI - Basic procedure of x-ray crystallography for analysis of lectin-sugar interactions. AB - Most three-dimensional structures of lectins have been determined by X-ray crystallography. This method determines the molecular structure using X-ray diffraction of a crystal, thereby providing structural information at the atomic level. In this chapter, an overview of the method for protein crystallography is briefly introduced, including a description of several techniques for analysis of the molecular and sugar-binding structure of lectins. PMID- 25117259 TI - A new structure determination method of lectins using a selenium-containing sugar ligand. AB - Phase determination is essential for solving X-ray crystal structures of proteins and their complexes. Conventional phase-determination methods using heavy atoms (Pt, Au, Hg, etc.) or the selenium (Se) atom are routinely utilized in structure determination of protein crystals. Here, we describe an alternative phase determination method for proteins such as lectins in which a Se-containing glycan is used as a ligand. In this technique, the Se atoms are simply introduced into the protein crystal as a complex, and the phase of the protein can be determined using anomalous signals from the Se-containing sugar. PMID- 25117260 TI - NMR analysis of carbohydrate-binding interactions in solution: an approach using analysis of saturation transfer difference NMR spectroscopy. AB - One of the most commonly used ligand-based NMR methods for detecting ligand binding is saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy. The STD NMR method is an invaluable technique for assessing carbohydrate-lectin interactions in solution, because STD NMR can be used to detect weak ligand binding (Kd ca. 10(-3)-10(-8) M). STD NMR spectra identify the binding epitope of a carbohydrate ligand when bound to lectin. Further, the STD NMR method uses 1H-detected NMR spectra of only the carbohydrate, and so only small quantities of non-labeled lectin are required. In this chapter, I describe a protocol for the STD NMR method, including the experimental procedures used to acquire, process, and analyze STD NMR data, using STD NMR studies for methyl-beta D-galactopyranoside (beta-Me-Gal) binding to the C-terminal domain of an R-type lectin from earthworm (EW29Ch) as an example. PMID- 25117261 TI - Small-angle X-ray scattering to obtain models of multivalent lectin-glycan complexes. AB - Recent advances in small-angle X-ray scattering (SAXS) have led to the ability to model the glycans on glycoproteins and to obtain the low-resolution solution structures of complexes of lectins bound to multivalent glycan-presenting scaffolds. This progress in SAXS can respond to the increasing interest in the biological action of glycoproteins and lectins and in the design of multivalent glycan-based antagonists. Carbohydrates make up a significant part of the X-ray scattering content in SAXS and should be included in the model together with the protein, whose structure is most often based on a crystal structure or NMR ensemble, to give a far-improved fit with the experimental data. The modeling of the spatial positioning of glycans on proteins or in the architecture of lectin glycan complexes delivers low-resolution structural information hitherto unmatched by any other method. SAXS data on the bacterial lectin FimH, strongly bound to heptyl alpha-D-mannose on a sevenfold derivatized beta-cyclodextrin, permitted determination of the stoichiometry of the complex and the geometry of the lectin deposition on the multivalent beta-cyclodextrin. The SAXS methods can be applied to larger complexes as the technique imposes no limit on the size of the macromolecular assembly in solution. PMID- 25117262 TI - Directed evolution of lectins by an improved error-prone PCR and ribosome display method. AB - Lectins are useful reagents for the structural characterization of glycans. However, currently available lectins have an apparent drawback in their "repertoire," lacking some critical probes, such as those for sulfated glycans. Thus, engineering lectins with novel specificity would be of great practical value. Here, we describe a directed evolution strategy to tailor novel lectins for novel specificity or biological functions. Our strategy uses a reinforced ribosome display-based selection combined with error-prone PCR to isolate mutants with target specificity and an evanescent-field fluorescence-assisted glycoconjugate microarray to rapidly evaluate the specificity of selected mutants. A successful case of screening a lectin, which has acquired an ability to recognize 6-sulfo-galactose-terminated glycans, is described. PMID- 25117263 TI - Tracing ancestral specificity of lectins: ancestral sequence reconstruction method as a new approach in protein engineering. AB - Protein evolution is a process of molecular design leading to the diversity of functional proteins found in nature. Recent advances in bioinformatics and structural biology, in addition to recombinant protein expression techniques, enable us to analyze more directly the molecular evolution of proteins by a new method using ancestral sequence reconstruction (ASR), the so-called experimental molecular archaeology. ASR has been used to reveal molecular properties and structures correlating with changing geology, ecology, and physiology, and to identify the structure elements important to changing physiological functions to fill substantial gaps in the processes of protein evolution. In this chapter, we describe ASR as a new method of protein engineering studies, and their application to analyzing lectins, of which evolutionary processes and structural features contributing to molecular stability, specificity, and unique functions have been elucidated. Experimental molecular archeology using ASR and crystal structures of full-length ancestral proteins is useful in understanding the evolutionary process of the functional and structural diversified lectins by tracing ancestral specificities. PMID- 25117264 TI - Comprehensive list of lectins: origins, natures, and carbohydrate specificities. AB - More than 100 years have passed since the first lectin ricin was discovered. Since then, a wide variety of lectins (lect means "select" in Latin) have been isolated from plants, animals, fungi, bacteria, as well as viruses, and their structures and properties have been characterized. At present, as many as 48 protein scaffolds have been identified as functional lectins from the viewpoint of three-dimensional structures as described in this chapter. In this chapter, representative 53 lectins are selected, and their major properties that include hemagglutinating activity, mitogen activity, blood group specificity, molecular weight, metal requirement, and sugar specificities are summarized as a comprehensive table. The list will provide a practically useful, comprehensive list for not only experienced lectin users but also many other non-expert researchers, who are not familiar to lectins and, therefore, have no access to advanced lectin biotechnologies described in other chapters. PMID- 25117265 TI - Lectin structures: classification based on the 3-D structures. AB - Recent progress in structural biology has elucidated the three-dimensional structures and carbohydrate-binding mechanisms of most lectin families. Lectins are classified into 48 families based on their three-dimensional structures. A ribbon drawing gallery of the crystal and solution structures of representative lectins or lectin-like proteins is appended and may help to convey the diversity of lectin families, the similarity and differences between lectin families, as well as the carbohydrate-binding architectures of lectins. PMID- 25117268 TI - Radiation induced base excision repair (BER): a mechanistic mathematical approach. AB - This paper presents a mechanistic model of base excision repair (BER) pathway for the repair of single-stand breaks (SSBs) and oxidized base lesions produced by ionizing radiation (IR). The model is based on law of mass action kinetics to translate the biochemical processes involved, step-by-step, in the BER pathway to translate into mathematical equations. The BER is divided into two subpathways, short-patch repair (SPR) and long-patch repair (LPR). SPR involves in replacement of single nucleotide via Pol beta and ligation of the ends via XRCC1 and Ligase III, while LPR involves in replacement of multiple nucleotides via PCNA, Pol delta/E and FEN 1, and ligation via Ligase I. A hallmark of IR is the production of closely spaced lesions within a turn of DNA helix (named complex lesions), which have been attributed to a slower repair process. The model presented considers fast and slow component of BER kinetics by assigning SPR for simple lesions and LPR for complex lesions. In the absence of in vivo reaction rate constants for the BER proteins, we have deduced a set of rate constants based on different published experimental measurements including accumulation kinetics obtained from UVA irradiation, overall SSB repair kinetic experiments, and overall BER kinetics from live-cell imaging experiments. The model was further used to calculate the repair kinetics of complex base lesions via the LPR subpathway and compared to foci kinetic experiments for cells irradiated with gamma rays, Si, and Fe ions. The model calculation show good agreement with experimental measurements for both overall repair and repair of complex lesions. Furthermore, using the model we explored different mechanisms responsible for inhibition of repair when higher LET and HZE particles are used and concluded that increasing the damage complexity can inhibit initiation of LPR after the AP site removal step in BER. PMID- 25117266 TI - Structural basis for constitutive activity and agonist-induced activation of the enteroendocrine fat sensor GPR119. AB - BACKGROUND AND PURPOSE: GPR119 is a Galphas-coupled 7TM receptor activated by endogenous lipids such as oleoylethanolamide (OEA) and by the dietary triglyceride metabolite 2-monoacylglycerol. GPR119 stimulates enteroendocrine hormone and insulin secretion. But despite massive drug discovery efforts in the field, very little is known about the basic molecular pharmacology of GPR119. EXPERIMENTAL APPROACH: GPR119 receptor signalling was studied in transfected cells. Mutational mapping (30 mutations in 23 positions) was performed on residues required for ligand-independent and agonist-induced GPR119 activation (AR231453 and OEA). Novel Rosetta-based receptor modelling was applied, using a composite template approach with segments from different X-ray structures and fully flexible ligand docking. KEY RESULTS: The increased signalling induced by increasing the cell surface expression of GPR119 in the absence of agonist and the inhibitory effect of two synthetic inverse agonists demonstrated that GRP119 signals with a high degree of constitutive activity through the Galphas pathway. The mutational maps for AR231453 and OEA were very similar and, surprisingly, also similar to the mutational map for residues affecting the constitutive signalling - albeit with key differences. Surprisingly, almost all residues in extracellular loop-2b were important for the constitutive activity. The molecular modelling and docking demonstrated that AR231453 binds in a 'vertical' pocket in between mutational hits reaching from the centre of the receptor out to extracellular loop-2b. CONCLUSIONS AND IMPLICATIONS: The high constitutive activity of GPR119 should be taken into account in future drug discovery efforts, which can now be guided by the detailed knowledge of the physiochemical properties of the extended ligand-binding pocket. PMID- 25117270 TI - Normative values of major SCAT2 and SCAT3 components for a college athlete population. AB - The Sports Concussion Assessment Tool-2 (SCAT2) is a posttrauma evaluative screener for concussion. Although a revised version (SCAT3) recently was released, the SCAT2 continues in use. Moreover, there have been no reports of normative values with college athletes with the SCAT2 or SCAT3. Similar to the SCAT3, the SCAT2 includes a 22-item self-report symptom scale, the Standardized Assessment of Concussion (SAC), and a hard surface-only version of the Balance Error Scoring System (BESS). The SCAT3 does not employ a total score and adds an optional gait component. The purpose of this study was to develop normative values for collegiate athletes on the SCAT2 and its subparts with respect to sex, collision risk by sport, and concussion history. In preseason, 477 college athletes (332 male, 145 female) completed the SCAT2. The average total score was 91.08 (SD = 5.60). The average number of symptoms endorsed was 1.75. Average SAC and BESS scores were 27.17 (SD = 2.01) and 25.64 (SD = 4.07), respectively. Little or no difference was found in total and component scores due to sex, sport type, or concussion history. When baseline measurement is lacking, these data provide a good benchmark for interpreting SCAT2 and SCAT3 performance. PMID- 25117269 TI - Do tree-ring stable isotope compositions faithfully record tree carbon/water dynamics? PMID- 25117271 TI - The use of FM dyes to analyze plant endocytosis. AB - FM (Fei-Mao) styryl dyes are compounds of amphiphilic character that are used for the fluorescence tracking of endocytosis and related processes, i.e., the internalization of membrane vesicles from the plasma membrane (PM) and dynamics of endomembranes. Staining with FM dyes and subsequent microscopical observations could be performed both on the tissue and cellular level. Here, we describe simple procedures for the effective FM dye staining and de-staining in root epidermal cells of Arabidopsis thaliana seedlings and suspension-cultured tobacco cells. The progression of FM dye uptake, reflected by an increased amount of the dye in the endosomal compartments, is monitored under the fluorescence microscope in a time-lapse manner. The data obtained can be used for the characterization of the rate of endocytosis and the function of components of endosomal recycling machinery. PMID- 25117267 TI - Evolution of nonclassical MHC-dependent invariant T cells. AB - TCR-mediated specific recognition of antigenic peptides in the context of classical MHC molecules is a cornerstone of adaptive immunity of jawed vertebrate. Ancillary to these interactions, the T cell repertoire also includes unconventional T cells that recognize endogenous and/or exogenous antigens in a classical MHC-unrestricted manner. Among these, the mammalian nonclassical MHC class I-restricted invariant T cell (iT) subsets, such as iNKT and MAIT cells, are now believed to be integral to immune response initiation as well as in orchestrating subsequent adaptive immunity. Until recently the evolutionary origins of these cells were unknown. Here we review our current understanding of a nonclassical MHC class I-restricted iT cell population in the amphibian Xenopus laevis. Parallels with the mammalian iNKT and MAIT cells underline the crucial biological roles of these evolutionarily ancient immune subsets. PMID- 25117272 TI - Sterol dynamics during endocytic trafficking in Arabidopsis. AB - Sterols are lipids found in membranes of eukaryotic cells. Functions of sterols have been demonstrated for various cellular processes including endocytic trafficking in animal, fungal, and plant cells. The ability to visualize sterols at the subcellular level is crucial to understand sterol distribution and function during endocytic trafficking. In plant cells, the polyene antibiotic filipin is the most extensively used tool for the specific detection of fluorescently labeled 3-beta-hydroxysterols in situ. Filipin can to some extent be used to track sterol internalization in live cells, but this application is limited, due to the inhibitory effects filipin exerts on sterol-dependent endocytosis. Nevertheless, filipin-sterol labeling can be performed on aldehyde fixed cells which allows for sterol detection in endocytic compartments. This approach can combine studies correlating sterol distribution with experimental manipulations of endocytic trafficking pathways. Here, we describe step-by-step protocols and troubleshooting for procedures on live and fixed cells to visualize sterols during endocytic trafficking. We also provide a detailed discussion of advantages and limitations of both methods. Moreover, we illustrate the use of the endocytic recycling inhibitor brefeldin A and a genetically modified version of one of its target molecules for studying endocytic sterol trafficking. PMID- 25117273 TI - Live microscopy analysis of endosomes and vesicles in tip-growing root hairs. AB - Tip growth is one of the most preferable models in the study of plant cell polarity; cell wall deposition is restricted mainly to a certain area of the cell, and cell expansion at this specific area leads to the development of tubular outgrowth. Tip-growing root hairs are well-established systems for such studies, because their lateral position within the root makes them easily accessible for experimental approaches and microscopic observations. Fundamental structural and molecular processes driving tip growth are exocytosis, endocytosis, and all aspects of vesicular and endosomal dynamic trafficking, as related to targeted membrane flow. Study of vesicles and endosomes in living root hairs, however, is rather difficult, due to their small size and due to the resolution limits of conventional light microscopes. Here we present noninvasive approaches for visualizing vesicular and endosomal compartments in the tip of growing root hairs using electronic light microscopy, contrast-enhanced video light microscopy, and confocal laser scanning microscopy (CLSM). These methods allow utilizing the maximum resolution of the light microscope. Together with protocols for appropriate preparation of living plant samples, the described methods should help improve our understanding on how tiny vesicles and endosomes support the process of tip growth in root hairs. PMID- 25117274 TI - Analysis of fluid-phase endocytosis in (intact) plant cells. AB - Endocytosis is a continuous process at the plasma membrane at least of all eukaryotic cells. Regardless of the molecular machinery, which drives the formation and uptake of endocytic vesicles, it is reasonable to assume that this process inevitably collects external fluid. Hence, at least for the majority of apoplastic solutes, the endocytosis of the fluid phase is likely to be an inevitable process. Due to its independence from the molecular machinery and low selectivity with respect to the cargo, it is thus perfectly suited to be used as a tracer to follow the activity of all endocytic events. Here we describe simple protocols based on fluorescence microscopy, which yield quantitative information about endocytic vesicle sizes-with sub-diffraction accuracy-as well as the size exclusion limits for these uptake routes. PMID- 25117275 TI - Immunogold labeling and electron tomography of plant endosomes. AB - High-resolution imaging of endosomal compartments and associated organelles can be achieved using state-of-the-art electron microscopy techniques, such as the combination of cryofixation/freeze-substitution for sample processing and electron tomography for three-dimensional (3D) analysis. This chapter deals with the main steps associated with these imaging techniques: selection of samples suitable for studying plant endosomes, sample preparation by high-pressure freezing/freeze-substitution, and electron tomography of plastic sections. In addition, immunogold approaches for identification of subcellular localization of endosomal and cargo proteins are also discussed. PMID- 25117277 TI - Analysis of Rab GTPase-effector interactions by bimolecular fluorescence complementation. AB - RAB GTPases interact with specific effector molecules in a spatiotemporally regulated manner to induce various downstream reactions. To clarify the overall picture of RAB GTPase functions, it is important to elucidate the cellular locale where RAB and its effectors interact. Here, we applied a bimolecular fluorescence complementation (BiFC) assay to analyze where RAB GTPase interacted with effectors in endosomal trafficking. PMID- 25117276 TI - Investigating protein-protein interactions in the plant endomembrane system using multiphoton-induced FRET-FLIM. AB - Real-time noninvasive fluorescence-based protein assays enable a direct access to study interactions in their natural environment and hence overcome the limitations of other methods that rely on invasive cell disruption techniques. The determination of Forster resonance energy transfer (FRET) by means of fluorescence lifetime imaging microscopy (FLIM) is currently the most advanced method to observe protein-protein interactions at nanometer resolution inside single living cells and in real-time. In the FRET-FLIM approach, the information gained using steady-state FRET between interacting proteins is considerably improved by monitoring changes in the excited-state lifetime of the donor fluorophore where its quenching in the presence of the acceptor is evidence for a direct physical interaction. The combination of confocal laser scanning microscopy with the sensitive advanced technique of time-correlated single photon counting allows the mapping of the spatial distribution of fluorescence lifetimes inside living cells on a pixel-by-pixel basis that is the same as the fluorescence image. Moreover, the use of multiphoton excitation particularly for plant cells provides further advantages such as reduced phototoxicity and photobleaching. In this protocol, we briefly describe the instrumentation and experimental design to study protein interactions within the plant endomembrane system, with a focus on the imaging of plant cells expressing fluorescent proteins and acquisition and analysis of fluorescence lifetime resolved data. PMID- 25117278 TI - In vivo imaging of brassinosteroid endocytosis in Arabidopsis. AB - Increasing evidence shows the involvement of endocytosis in specific signaling outputs in plants. To better understand the interplay between endocytosis and signaling in plant systems, more ligand-receptor pairs need to be identified and characterized. Crucial for the advancement of this research is also the development of imaging techniques that allow the visualization of endosome associated signaling events at a high spatiotemporal resolution. This requires the establishment of tools to track ligands and their receptors by fluorescence microscopy in living cells. The brassinosteroid (BR) signaling pathway has been among the first systems to be characterized with respect to its connection with endocytic trafficking, owning to the fact that a fluorescent version of BR, Alexa Fluor 647-castasterone (AFCS) has been generated. AFCS and the fluorescently tagged BR receptor, BR INSENSITIVE1 (BRI1) have been used for the specific detection of BRI1-AFCS endocytosis and for the delineation of their endocytic route as being clathrin-mediated. AFCS was successfully applied in functional studies in which pharmacological rerouting of the BRI1-BR complex was shown to have an impact on signaling. Here we provide a method for the visualization of endocytosis of plant receptors in living cells. The method was used to track endocytosis of BRI1-BR complexes in Arabidopsis epidermal root meristem cells by using fluorescent BRs. Pulse-chase experiments combined with quantitative confocal microscopy were used to determine the internalization rates of BRs. This method is well suited to measure the internalization of other plant receptors if fluorescent ligands are available. PMID- 25117279 TI - Analysis of prevacuolar compartment-mediated vacuolar proteins transport. AB - Transient expression using protoplasts is a quick and powerful tool for studying protein trafficking and subcellular localization in plant cells. Prevacuolar compartments (PVCs) or multivesicular bodies (MVBs) are intermediate compartments that mediate protein transport between late Golgi or trans-Golgi network (TGN) and vacuole. Both wortmannin treatment and ARA7(Q69L) expression can induce PVC homotypic fusion and PVC enlargement in plant cells. Here, we describe detailed protocols to use transient expression of protoplasts derived from Arabidopsis suspension culture cells for studying protein trafficking and localization. Using three GFP-tagged vacuolar cargo proteins and RFP-tagged PVC membrane marker as examples, we illustrate the major tools and methods, including wortmannin treatment, ARA7(Q69L) expression and immunoblot analysis, to analyze PVC-mediated vacuolar protein transport in plant cells. PMID- 25117280 TI - Evaluation of defective endosomal trafficking to the vacuole by monitoring seed storage proteins in Arabidopsis thaliana. AB - Vacuolar proteins are synthesized as precursor forms in the endoplasmic reticulum and are sorted to the vacuole. In this chapter, we introduce two easy methods for the evaluation of vacuolar protein transport using Arabidopsis seeds. These methods are adequate to detect defects in vacuolar transport mediated by endosomes and other trafficking pathways as well. They include an immunoblot assay that monitors the abnormal accumulation of storage protein precursors, and an immunogold labeling assay that monitors the abnormal secretion of storage proteins. Each method facilitates the rapid identification of defects in the transport of endogenous vacuolar proteins in Arabidopsis mutants. PMID- 25117281 TI - Trans-species complementation analysis to study function conservation of plant Endosomal Sorting Complex Required for Transport (ESCRT) proteins. AB - ESCRT (Endosomal Sorting Complex Required for Transport) proteins are required for the sorting of biosynthetic and endocytic proteins at multivesicular bodies (MVBs). Here, I describe an assay to evaluate conservation of endosomal sorting functions of plant ESCRT proteins by trans-species complementation analysis. The assay is based on the imaging of a fluorescent biosynthetic MVB cargo, the carboxypeptidase S (CPS) fused to the green fluorescent protein GFP, in yeast ESCRT mutants expressing putative plant orthologues of the missing yeast ESCRT components. PMID- 25117282 TI - A re-elicitation assay to correlate flg22-signaling competency with ligand induced endocytic degradation of the FLS2 receptor. AB - In the model plant Arabidopsis, the best studied Pattern-triggered immunity (PTI) system is perception of the bacterial pathogen-associated molecular pattern (PAMP) flagellin, or its active peptide-derivative flg22, by the plasma membrane localized receptor FLAGELLIN SENSING 2 (FLS2). Flg22 perception initiates an array of immune responses including the fast and transient production of reactive oxygen species (ROS). In addition, FLS2 undergoes ligand-induced endocytosis and subsequent degradation within 60 min of flg22-treatment. Luminol-based assays are routinely used to measure extracellular ROS production within minutes after flg22 treatment. Many mutants in flg22-response pathways display defects in flg22 induced ROS production. Here, we describe a luminol-based ROS Re-elicitation Assay that can be utilized to quantitatively assess flg22-signaling competency of FLS2 at times during which FLS2 is internalized, trafficked through endosomal compartments, and degraded in response to flg22. This assay may also be employed to correlate FLS2 signaling competency with receptor accumulation in vesicular trafficking mutants that either affect FLS2 endocytosis or replenishment of FLS2 through the secretory pathway. In addition, this assay can be extended to studies of other PAMP (ligand)-receptor pairs. PMID- 25117283 TI - Preparation of enriched plant clathrin-coated vesicles by differential and density gradient centrifugation. AB - Methods for the subcellular fractionation and enrichment of specific intracellular compartments are essential tools in the analysis of compartment composition and function. In vitro characterization of isolated cell organelles and other endomembrane intermediates, including exploration of the compartment protein ensemble, offers strong clues of in vivo function identity. Here, we describe methodology for the isolation of clathrin-coated vesicles from Arabidopsis thaliana suspension-cultured cells on the basis of differential and density centrifugation. PMID- 25117284 TI - Proteomics of endosomal compartments from plants case study: isolation of trans Golgi network vesicles. AB - A detailed understanding of endomembrane processes and their biological roles is vital for a complete picture of plant growth and development; however their highly dynamic nature has complicated comprehensive and rigorous studies so far. Recent pioneering efforts have demonstrated that isolation of vesicles in their native state, paired with a quantitative identification of their cargo, offers a viable and practicable approach for the dissection of endomembrane trafficking pathways. The protocol presented in this chapter describes in detail the isolation of the SYP61 trans-Golgi network vesicles from Arabidopsis. With minor alterations, in a few key parameters, it can be adopted to yield a universal procedure for the broad spectrum of plant vesicles. PMID- 25117285 TI - Analysis of global ubiquitylation and ubiquitin-binding domains involved in endosomal trafficking. AB - Ubiquitylation is a reversible posttranslational modification that regulates various cellular pathways. Ubiquitylation of a plasma membrane protein was shown to serve as a signal for endocytosis of plasma membrane proteins in yeast and mammals as well as in plants. As more and more plant plasma membrane proteins are reported to be regulated through their ubiquitylation status, methods to analyze ubiquitylation and ubiquitin binding would be useful for the characterization of proteins involved in endocytosis of ubiquitylated cargo proteins. PMID- 25117286 TI - Analysis of endocytosis and ubiquitination of the BOR1 transporter. AB - Endocytosis and membrane trafficking are the major factors controlling the abundance of plasma membrane proteins, such as transporters and receptors. We have found that Arabidopsis borate transporter BOR1 is polarly localized to the inner (stele-facing) plasma membrane domain of various root cells under boron limitation, and when boron is supplied in excess, BOR1 is rapidly transferred to the vacuole for immediate degradation. The BOR1 polarity and degradation are controlled by membrane trafficking including endocytosis. In this chapter, we describe methods for observation of endocytic trafficking of BOR1, and detection of BOR1 ubiquitination that is required for vacuolar sorting for degradation. PMID- 25117288 TI - Ubiquitylation-mediated control of polar auxin transport: analysis of Arabidopsis PIN2 auxin transport protein. AB - Reversible, covalent modification by the small protein ubiquitin acts in a variety of pathways controlling protein fate in virtually all aspects of cellular function. For example, ubiquitylation of plasma membrane proteins modulates their intracellular sorting and turnover, thereby decisively influencing crosstalk between cells and their environment. In recent years, experimental work performed with the model plant Arabidopsis thaliana demonstrated ubiquitylation of a number of plasma membrane proteins, including the auxin efflux carrier protein PIN2. By using solubilized membrane protein immunoprecipitation assays, we established quantitative approaches, suitable for analysis of PIN2 ubiquitylation and variations therein. Applicability of this robust approach is not restricted to PIN auxin carriers, but could be extended to analysis of further plant membrane proteins that are controlled by variations in their ubiquitylation status. PMID- 25117289 TI - Chemical genomics screening for biomodulators of endomembrane system trafficking. AB - Cell proteins traffic through complex and tightly regulated pathways. Although the endomembrane system is essential, its different pathways are still not well understood. In order to dissect protein trafficking pathways, chemical genomic screenings have been performed. This strategy has been utilized to successfully discover bioactive chemicals with a specific cellular action and in most cases, tunable and reversible effects. Once the bioactive chemical is identified, further strategies can be used to find the target proteins that are important for functionality of trafficking pathways. This approach can be combined with the powerful genetic tools available for model organisms. Drug-hypersensitive and drug-resistant mutant isolation can lead to the identification of cellular pathways affected by a bioactive chemical and reveal its protein target(s). Here, we describe an approach to look for hypersensitive and resistant mutants to a specific bioactive chemical that affects protein trafficking in yeast. This approach can be followed and adapted to any other pathway or cellular process that can be screened phenotypically, serving as a guide for novel screens in yeast. More importantly, information provided by this approach can potentially be extrapolated to other organisms like plants. Thus, the method described can be of broad utility to plant biologists. PMID- 25117287 TI - Ubiquitination of plant immune receptors. AB - Ubiquitin is a highly conserved regulatory protein consisting of 76 amino acids and ubiquitously expressed in all eukaryotic cells. The reversible ubiquitin conjugation to a wide variety of target proteins, a process known as ubiquitination or ubiquitylation, serves as one of the most important and prevalent posttranslational modifications to regulate the myriad actions of protein cellular functions, including protein degradation, vesicle trafficking, and subcellular localization. Protein ubiquitination is an ATP-dependent stepwise covalent attachment of one or more ubiquitin molecules to target proteins mediated by a hierarchical enzymatic cascade consisting of an E1 ubiquitin activating enzyme, E2 ubiquitin-conjugating enzyme, and E3 ubiquitin ligase. The plant plasma membrane resident receptor-like kinase Flagellin Sensing 2 (FLS2) recognizes bacterial flagellin and initiates innate immune signaling to defend against pathogen attacks. We have recently shown that two plant U-box E3 ubiquitin ligases PUB12 and PUB13 directly ubiquitinate FLS2 and promote flagellin-induced FLS2 degradation, which in turn attenuates FLS2 signaling to prevent excessive or prolonged activation of immune responses. Here, we use FLS2 as an example to describe a protocol for detection of protein ubiquitination in plant cells in vivo and in test tubes in vitro. In addition, we elaborate the approach to identify different types of ubiquitin linkages by using various lysine mutants of ubiquitin. The various in vivo and in vitro ubiquitination assays will provide researchers with the tools to address how ubiquitination regulates diverse cellular functions of target proteins. PMID- 25117290 TI - Integrative chemical proteomics and cell biology methods to study endocytosis and vesicular trafficking in Arabidopsis. AB - We present a comprehensive approach combining proteomics and cell biology to study vesicular trafficking in plants. Within this approach, we exploit chemical compounds inhibiting particular vesicular trafficking events in plant cells. Treatment of plants with these relatively specific inhibitors results in intracellular accumulation of proteins being transported by vesicles as well as in a change in abundance of regulatory proteins. Such pharmacological inhibition allows for identification of key proteins, and for further detailed functional investigation using cell biological, molecular biological, and biochemical methods used for validation of proteomic results. PMID- 25117291 TI - Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric artery. AB - BACKGROUND AND PURPOSE: Previous studies have demonstrated that nicotine releases protons from adrenergic nerves via stimulation of nicotinic ACh receptors and activates transient receptor potential vanilloid-1 (TRPV1) receptors located on calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves, resulting in vasodilatation. The present study investigated whether perivascular nerves release protons, which modulate axon-axonal neurotransmission. EXPERIMENT APPROACH: Perfusion pressure and pH levels of perfusate in rat-perfused mesenteric vascular beds without endothelium were measured with a pressure transducer and a pH meter respectively. KEY RESULTS: Periarterial nerve stimulation (PNS) initially induced vasoconstriction, which was followed by long lasting vasodilatation and decreased pH levels in the perfusate. Cold-storage denervation of the preparation abolished the decreased pH and vascular responses to PNS. The adrenergic neuron blocker guanethidine inhibited PNS-induced vasoconstriction and effects on pH, but not PNS-induced vasodilatation. Capsaicin (CGRP depletor), capsazepine and ruthenium red (TRPV1 inhibitors) attenuated the PNS-induced decrease in pH and vasodilatation. In denuded preparations, ACh caused long-lasting vasodilatation and lowered pH; these effects were inhibited by capsaicin pretreatment and atropine, but not by guanethidine or mecamylamine. Capsaicin injection induced vasodilatation and a reduction in pH, which were abolished by ruthenium red. The use of a fluorescent pH indicator demonstrated that application of nicotine, ACh and capsaicin outside small mesenteric arteries reduced perivascular pH levels and these effects were abolished in a Ca(2+) -free medium. CONCLUSION AND IMPLICATION: These results suggest that protons are released from perivascular adrenergic and CGRPergic nerves upon PNS and these protons modulate transmission in CGRPergic nerves. PMID- 25117292 TI - Actigraphy and Sleep Diary Measurements in Breast Cancer Survivors: Discrepancy in Selected Sleep Parameters. AB - This analysis examined the discrepancy between sleep diary and actigraphy measurements in breast cancer survivors (BCS) with insomnia. BCS from communities in Western U.S. provided demographic/medical information, insomnia, mood, and fatigue data at baseline. Averaged over 5 weeks, actigraphy measured 55.75 minutes (SD = 112.42) less total sleep time (TST), and 85.19 minutes (SD = 81.36) more wake after sleep onset (WASO) than diaries. Some women showed agreement between measures; others were more variable. There were no significant relationships between TST and WASO discrepancy and participant characteristics. There may be sleep differences in BCS that results in greater perceived TST and less WASO reported in diaries. Measurements discrepancy is a significant concern needing further evaluation of medical populations with insomnia. PMID- 25117294 TI - Anti-CCR4 monoclonal antibody mogamulizumab for the treatment of EBV-associated T and NK-cell lymphoproliferative diseases. AB - PURPOSE: Epstein-Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells, and T- and NK-cell lymphoproliferative diseases (T/NK LPD) that are refractory to conventional chemotherapies may develop. To identify a molecular-targeted therapy for EBV-associated T/NK-LPDs, we investigated whether CC chemokine receptor 4 (CCR4) was expressed on EBV-infected T and/or NK cells and whether a humanized anti-CCR4 monoclonal antibody, mogamulizumab, was effective. EXPERIMENTAL DESIGN: CCR4 expression was examined in various cell lines. In vitro, the effects of mogamulizumab on cell lines were evaluated in the presence of peripheral blood mononuclear cells from volunteers. In vivo, the effects of mogamulizumab were evaluated using a murine xenograft model. CCR4 expression was examined on EBV-infected cells from patients with EBV-associated T/NK-LPDs. Ex vivo, the effects of mogamulizumab were evaluated using patient lymphocytes. RESULTS: CCR4 expression was confirmed in most EBV-positive T and NK cell lines. Mogamulizumab induced antibody-dependent cellular cytotoxicity (ADCC) activity against CCR4-positive cell lines, and inhibited the growth of EBV positive NK-cell lymphomas in a murine xenograft model. Furthermore, CCR4 was expressed on EBV-infected cells in 8 of 17 patients with EBV-associated T/NK LPDs. Interestingly, CCR4 was positive in 5 of 5 patients with hydroa vacciniforme, a photodermatosis caused by the clonal expansion of EBV-infected gammadeltaT cells. EBV-positive gammadeltaT cells were obtained from a patient with hydroa vacciniforme and subjected to an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. The gammadeltaT cells that were positive for CCR4 were killed by mogamulizumab via ADCC. CONCLUSIONS: These results indicate that mogamulizumab may be a therapeutic option against EBV-associated T/NK-LPDs. PMID- 25117300 TI - An abrasion-resistant and broadband antireflective silica coating by block copolymer assisted sol-gel method. AB - A double-layer broadband antireflective (AR) coating was prepared on glass substrate via sol-gel process using two kinds of acid-catalyzed TEOS-derived silica sols. The relative dense layer with a porosity of ~10% was obtained from an as-prepared sol, while the porous layer with a porosity of ~55% was from a modified one with block copolymer (BCP) Pluronic F127 as template which results in abundant ordered mesopores. The two layers give rise to a reasonable refractive index gradient from air to the substrate and thus high transmittance in a wide wavelength range, and both of them have the same tough skeleton despite different porosity, for which each single-layer and the double-layer coatings all behaved well in the mechanical property tests. The high transmittance and the strong ability of resisting abrasion make this coating promising for applications in some harsh conditions. In addition, the preparation is simple, low-cost, time saving, and flexible for realizing the optical property. PMID- 25117299 TI - Cumulative effects of genetic markers and the detection of advanced colorectal neoplasias by population screening. AB - Genetic markers associated with colorectal cancer may be used in population screening for the early identification of patients at elevated risk of disease. We genotyped 3059 individuals with no cancer family history for eight markers previously associated with colorectal cancer. After colonoscopy, the genetic profile of cases with advanced colorectal neoplasia (213) was compared with the rest (2846). rs2066847 and rs6983267 were significantly associated with the risk of advanced colorectal neoplasia but with limited effect on their own [odds ratio (OR) 1.59; 95% confidence interval (CI) 1.02-2.41; p = 0.033 and OR 1.45; 95% CI 1.02-2.12; p = 0.044, respectively]. Cumulative effects, in contrast, were associated with high risk: the combination of rs2066847, rs6983267, rs4779584, rs3802842 and rs4939827 minimized the number of markers considered, while maximizing the relative size of the carrier group and the risk associated to it, for example, for at least two cumulated risk markers, OR is 2.57 (95% CI 1.50 4.71; corrected p-value 0.0079) and for three or more, OR is 3.57 (95% CI 1.91 6.96; corrected p-value 0.00074). The identification of cumulative models of - otherwise - low-risk markers could be valuable in defining risk groups, within an otherwise low-risk population (no cancer family history). PMID- 25117293 TI - Combined inhibition of Wee1 and PARP1/2 for radiosensitization in pancreatic cancer. AB - PURPOSE: While the addition of radiation to chemotherapy improves survival in patients with locally advanced pancreatic cancer, more effective therapies are urgently needed. Thus, we investigated the radiosensitizing efficacy of the novel drug combination of Wee1 and PARP1/2 inhibitors (AZD1775 and olaparib, respectively) in pancreatic cancer. EXPERIMENTAL DESIGN: Radiosensitization of AsPC-1 or MiaPaCa-2 human pancreatic cancer cells was assessed by clonogenic survival and tumor growth assays. Mechanistically, the effects of AZD1775, olaparib, and radiation on cell cycle, DNA damage (gammaH2AX), and homologous recombination repair (HRR) were determined. RESULTS: Treatment of AsPC-1 and MiaPaCa-2 cells with either AZD1775 or olaparib caused modest radiosensitization, whereas treatment with the combination significantly increased radiosensitization. Radiosensitization by the combination of AZD1775 and olaparib was associated with G2 checkpoint abrogation and persistent DNA damage. In addition, AZD1775 inhibited HRR activity and prevented radiation-induced Rad51 focus formation. Finally, in vivo, in MiaPaCa-2-derived xenografts, olaparib did not radiosensitize, whereas AZD1775 produced moderate, yet significant, radiosensitization (P < 0.05). Importantly, the combination of AZD1775 and olaparib produced highly significant radiosensitization (P < 0.0001) evidenced by a 13-day delay in tumor volume doubling (vs. radiation alone) and complete eradication of 20% of tumors. CONCLUSIONS: Taken together, these results demonstrate the efficacy of combined inhibition of Wee1 and PARP inhibitors for radiosensitizing pancreatic cancers and support the model that Wee1 inhibition sensitizes cells to PARP inhibitor-mediated radiosensitization through inhibition of HRR and abrogation of the G2 checkpoint, ultimately resulting in unrepaired, lethal DNA damage and radiosensitization. Clin Cancer Res; 20(19); 5085-96. (c)2014 AACR. PMID- 25117301 TI - Administration of commercial Rhodococcus equi specific hyperimmune plasma results in variable amounts of IgG against pathogenic bacteria in foals. AB - Rhodococcus equi is the most common cause of pneumonia in young foals. A vaccine is not available and the use of R equi-specific hyperimmune plasma (HIP) is common. Despite its widespread use, the efficacy of HIP in preventing disease remains controversial. The objectives of this study were (1) to evaluate the virulence associate protein A (VapA)-specific IgG and IgG subclasses in commercially available R equi HIP and (2) to evaluate serum VapA-specific IgG and IgG subclasses in foals following administration of commercial R equi HIP. Three different lots from four commercial R equi HIP were sampled. VapA-specific IgG and IgG subclasses were evaluated in all samples using an ELISA. Serum was collected from newborn foals either after commercial R equi HIP was administered (n=97) or not (n=70). Serum was also collected from each mare. Administration of HIP significantly (P<0.001) increased VapA-specific IgGs in recipient foals, however, there was a marked variation in VapA-specific IgGs in foals receiving the same product. VapA-specific IgGs were significantly different (P<0.001) between products and varied between lots, with coefficients of variation ranging from 17 to 123 per cent. These results may explain previously reported disparities in HIP efficacy. PMID- 25117303 TI - Cross-leg repair of large soft-tissue defects in distal sites of the feet by distally based neuro-fasciocutaneous flaps with perforating vessels. AB - The objective of this study was to introduce a method for repairing large soft tissue defects on the foot. Distally based neuro-fasciocutaneous flaps with perforating vessels were designed along the saphenous and sural neurovascular axes. The cutaneous perforating branches of the major arteries of the lower extremities were used as pedicles, which provided a rotation arc for the cross leg flap to cover the large-sized soft-tissue defects on the foot. We transferred 6 neurocutaneous vascular axial flaps, including 4 saphenous neurocutaneous axial flaps (ranging from 25 x 13 to 17 x 9 cm in area) with posterior tibial perforators as the pedicle, and 2 sural neurocutaneous axial flaps (ranging from 29 x 12 to 18 x 7 cm in area) supplied by the perforating branches of the peroneal vessels. These 6 cases of neuro-fasciocutaneous flaps survived with satisfactory cosmetic appearances and functional results on follow-up at 8 to 17 months post-surgery. Placing a distally based neuro-fasciocutaneous cross-leg flap with perforating vessels is an effective method for repairing large-sized soft-tissue defects on the foot. PMID- 25117302 TI - Increased serum levels of GDF-15 associated with mortality and subclinical atherosclerosis in patients on maintenance hemodialysis. AB - BACKGROUND/AIMS: Increased carotid intima-media thickness (CIMT) was shown to be an independent predictor of cardiovascular (CV) mortality in dialysis patients and the general population. Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor superfamily, is produced by cardiomyocytes and atherosclerotic lesions under stress conditions such as inflammation. We assessed associations between serum concentrations of GDF-15, mortality, and CIMT for subclinical atherosclerosis in hemodialysis (HD) patients. METHODS: A total of 87 patients on maintenance hemodialysis and 45 sex- and age-matched healthy controls were included in this prospective study. Serum GDF-15 levels were measured by ELISA. CIMT was assessed by Doppler ultrasonography. The association between serum GDF-15 levels and mortality was assessed using Cox regression analysis with serum levels categorized into two groups according to the median value (328.18 pg/ml). Patients were followed for 2 years and cause-specific and all-cause mortality were determined. RESULTS: The median level of serum GDF-15 was significantly higher in HD patients than controls [328 (198-522) vs. 176 (101 289) pg/ml, p < 0.01, respectively]. Serum GDF-15 levels were correlated to CIMT (r = 0.607, p < 0.001), C-reactive protein (CRP; r = 0.250, p = 0.010), HD duration (r = 0.376, p = 0.004), and serum albumin (r = - 0.156, p = 0.030). The multivariate analysis revealed that GDF-15 was found to be an independent variable of CIMT in HD patients. In the study, the serum GDF-15 level was an independent marker of all-cause of mortality when adjusted for age, CRP, and history of diabetes mellitus. CONCLUSION: The relationship between serum GDF-15, mortality, and carotid artery thickening suggests that GDF-15 may be a novel marker of atherosclerosis, inflammation, and malnutrition in HD patients. PMID- 25117304 TI - Assessment of microsatellites in estimating inter- and intraspecific variation among Neotropical Crocodylus species. AB - We tested microsatellites that were developed for the saltwater crocodile (Crocodylus porosus) for cross-species amplification and to provide an estimate of inter- and intraspecific variation among four species of Neotropical crocodiles (C. rhombifer, C. intermedius, C. acutus, and C. moreletii). Our results indicated that with the exception of 2 loci in C. intermedius, all 10 microsatellite loci were successfully amplified in the 4 species, producing a set of variably sized alleles that ranged in number between 2 and 14 alleles per locus. Similarly, private alleles (i.e., unique alleles) also were reported in all 4 species for at least 3 loci. The mean observed and expected heterozygosities (averaged across species for all 10 loci combined) ranged from 0.39 to 0.77 and from 0.44 to 0.78, respectively. In addition to this, we evaluated these microsatellites in 2 populations of C. acutus and C. moreletii to assess their utility in estimating intraspecific levels of polymorphisms. These microsatellites also showed considerable allelic variation in population level analysis. The set of 10 microsatellite loci in our study had the potential to be used as a tool in population and conservation genetic studies of Neotropical crocodiles. PMID- 25117305 TI - Development of polymorphic expressed sequence tag-single sequence repeat markers in the common Chinese cuttlefish, Sepiella maindroni. AB - The common Chinese cuttlefish (Sepiella maindroni) is one of the popular edible cephalopod consumed across Asia. To facilitate the population genetic investigation of this species, we developed fourteen polymorphic microsatellite makers from expressed sequence tags of S. maindroni. The number of alleles at each locus ranged from 6 to 10 with an average of 7.9 alleles per locus. The ranges of observed and expected heterozygosity were from 0.615 to 0.962 and 0.685 to 0.888, respectively. Four loci were found deviated significantly from Hardy Weinberg equilibrium. The polymorphism information content ranged from 0.638 to 0.833. These polymorphic microsatellite loci will be helpful for the population genetic, genetic linkage map, and other genetic studies of S. maindroni. PMID- 25117306 TI - Molecular identification of Amazonian stingless bees using polymerase chain reaction single-strand conformation polymorphism. AB - In countries containing a mega diversity of wildlife, such as Brazil, identifying and characterizing biological diversity is a continuous process for the scientific community, even in face of technological and scientific advances. This activity demands initiatives for the taxonomic identification of highly diverse groups, such as stingless bees, including molecular analysis strategies. This type of bee is distributed in all of the Brazilian states, with the highest species diversity being found in the State of Amazonia. However, the estimated number of species diverges among taxonomists. These bees are considered the main pollinators in the Amazon rainforest, in which they obtain food and shelter; however, their persistence is constantly threatened by deforestation pressure. Hence, it is important to classify the number and abundance of bee specie, to measure their decline and implement meaningful, priority conservation strategies. This study aims to maximize the implementation of more direct, economic and successful techniques for the taxonomic identification of stingless bees. Specifically, the genes 16S rRNA and COI from mitochondrial DNA were used as molecular markers to differentiate 9 species of Amazonian stingless bees based on DNA polymorphism, using the polymerase chain reaction-single-strand conformation polymorphism technique. We registered different, exclusive SSCP haplotypes for both genes in all species analyzed. These results demonstrate that SSCP is a simple and cost-effective technique that is applicable to the molecular identification of stingless bee species. PMID- 25117307 TI - Regulatory effect of iron regulatory protein-2 on iron metabolism in lung cancer. AB - Iron metabolism plays an important role in the pathogenesis of lung cancer. This study aimed to investigate the effect of gene silencing of iron regulatory protein-2 (IRP2) on mRNA and protein expression of transferrin (Tf), transferrin receptor (TfR), and ferritin (Fn) in A549 lung cancer cells. A549 cells were cultured and divided into a liposome control group, a liposome + oligonucleotide (SCODN) control group, and a Lipofectamine + antisense oligonucleotide (ASODN) group. RT-PCR and Western blotting were used to detect mRNA and protein expression of Tf, TfR, and Fn. We found no significant change in Tf mRNA expression among the 3 groups (P = 0.078). TfR and Fn mRNA expressions in the ASODN group notably decreased compared to the liposome and SCODN groups (P < 0.01). IRP2 and TfR protein expressions in the ASODN group were significantly lower than in the liposome or SCODN groups (P < 0.05), whereas no significant change in Tf protein expression was observed between the 3 groups (P = 0.088). Fn protein expression in the ASODN group was significantly higher than in the liposome or SCODN group (P < 0.05). IRP2 can regulate the expression of TfR and Fn by changing its own protein expression and thereby regulate iron metabolism. PMID- 25117308 TI - Treatment of seawater immersion-complicated open-knee joint fracture. AB - The current study aimed to select suitable remedies for seawater immersion complicated open-knee joint fracture by exploring the effects of different treatment methods. Forty adult rabbits weighing 2.20 +/- 0.25 kg were divided equally into internal fracture fixation group (A), seawater-immersed group with primary internal fixation (B), seawater-immersed group with secondary internal fixation (C), and seawater-immersed group with external fixation (D), using the random-digit table method. Open-femoral internal condylar fracture models were established. Group A was left untreated for 2 h, whereas the other three groups were subjected to seawater immersion for 2 h. Afterwards, groups A and B underwent debridement and steel plate and screw internal fixation. Group C underwent debridement and external fixation, which was followed by secondary steel plate and screw internal fixation after the wound healed. Group D underwent transarticular arthrodesis. Wound infection, joint functional rehabilitation, and radiological and histopathological changes in fracture healing in each group were assessed. The results showed that delayed internal fixation effectively reduces the infection rate of seawater immersion-complicated open fracture and benefits joint function rehabilitation. PMID- 25117309 TI - Prostate stem cell antigen rs2294008 (C>T) polymorphism and bladder cancer risk: a meta-analysis based on cases and controls. AB - Several published articles have evaluated the association between the prostate stem cell antigen (PSCA) rs2294008 (C>T) polymorphism and bladder cancer risk, but the results remain inconclusive. In order to derive a more precise estimation of the association, we performed a meta-analysis of four case-control studies that included 9617 cases and 16,323 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Our meta-analysis showed that, overall, the rs2294008 (C>T) polymorphism was associated with bladder cancer susceptibility (OR = 1.29, 95%CI = 1.20-1.40 for TT vs CC; OR = 1.24, 95%CI = 1.16-1.31 for CT vs CC; OR = 1.25, 95%CI = 1.18-1.33 for TT/CT vs CC; OR = 1.13, 95%CI = 1.06-1.20 for TT vs CT/CC). In the stratified analyses, the risk remained significant for studies of European populations, Asian populations, population-based studies, and hospital-based studies. In conclusion, the results suggest that the PSCA rs2294008 (C>T) polymorphism is a risk factor for bladder cancer development. PMID- 25117310 TI - Experimental strategies in performing value for cultivation and use experiments for the tobacco crop II: dimension of the experimental network. AB - In this study, we aimed to establish strategies for value for cultivation and use (VCU) experiments for the tobacco crop in the southern region of Brazil with respect to the number of environments used to assess tobacco lines. Trials of the Virginia (18 sites) and Burley (17 sites) varietal groups were conducted in the three states of the southern region of Brazil in the 2009-2010 crop season. The experiment was conducted in a completely randomized block design with four replications of 10 tobacco lines in the final stage of evaluation; the plots had 6 rows of 7 plants each, or 42 plants per plot. The cured leaf weight per hectare (kg/ha) was obtained. To evaluate stability, the ecovalence and additive main effects and multiplicative interaction models were adopted. In addition, joint analyses of variance were carried out considering different site numbers by simulating resampling. The site number ranged from 2 to 17 or 2 to 16, depending on the varietal group, and sites were selected at random without replacement. The process was repeated 2000 times for each number of sites. All analyses were performed using the R software. The results are very similar for both varietal groups. There is no advantage of using a large number of sites for VCU experiments in the southern region of Brazil because many sites contributed little to the interaction or did not discriminate the tobacco lines. Furthermore, the classification of the best lines is very similar to that obtained in the total number of evaluated sites. PMID- 25117311 TI - Association between EGF and VEGF functional polymorphisms and sporadic colorectal cancer in the Malaysian population. AB - Growth factors are polypeptides that are critical for the initiation, progression, and metastasis of cancer. Most tumor cells are capable of synthesizing particular growth factors leading to constitutive pathway activation in these cells through autocrine signaling. Epidermal growth factor (EGF) is a potent mitogenic peptide that exerts direct effects on the proliferation and differentiation of tumor cells in carcinogenesis. By contrast, vascular endothelial growth factor (VEGF) is vital for the invasion and metastasis of neoplasms through the formation of new blood vessels from mature endothelial cells. In this study, we investigated the association between functional polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC) susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this case-control study. Genotyping of genetic variants was conducted via real-time polymerase chain reaction (PCR) amplification with allele specific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936 C>T variants was significantly associated with CRC susceptibility among the Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation between these functional polymorphisms and CRC risk was found in this Malaysian population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce, and the results reported thus far differ from one population to another. Hence, more replication studies are warranted before any firm conclusions can be made. PMID- 25117312 TI - Development of eight novel microsatellite markers for Huoyan geese. AB - In this study, we isolated microsatellite DNA from the Huoyan goose genome with magnetic beads. As a result, 150 positive clones were identified, and 148 microsatellites were found. Among the 148 microsatellites, 69.6% were perfect, 17.6% were imperfect, and the rest were compound type (12.8%). Twenty microsatellite primers were used to screen 90 individuals from 3 Huoyan goose populations. Eight loci were polymorphic with a low number of alleles (2 to 4). The observed and expected heterozygosities ranged from 0.3556 to 1 and from 0.2923 to 0.6868, respectively. All the 8 polymorphic loci were in Hardy-Weinberg equilibrium. These molecular markers will be useful for future studies on population genetic structure and conservation genetics in Huoyan geese. PMID- 25117313 TI - Comparison of methods for estimates of molecular genetic diversity in genus Croton: influence of coefficients, clustering strategies and data projection. AB - We investigated 10 similarity (and disimilarity) coefficients in a set of 40 wild genotypes of Croton linearifolius subjected to analyses using hierarchical grouping methods, grouping methods by optimization and data projection in two dimensional space. Genotypes were characterized by analyzing DNA polymorphism with the use of 15 ISSR and 12 RAPD markers. The distance measurements were compared by the Spearman correlation test, projection in two-dimensional space and grouping efficiency evaluation. The Spearman correlation coefficients between the 10 coefficients evaluated were significant (P < 0.001) and indicated significant changes in genotype ranking due to type of coefficient used (0.76 <= rs <= 1). Wide variation was also observed in the efficiency of clustering methods, where the unweighted pair group method with arithmetic mean was the most suitable (0.3 <= D <= 1.5 ; 0.41 <= rc <= 0.77; 5.99 <= S <= 12.61). Projection efficiencies in two-dimensional space showed high-stress values (65 < S < 89%). Similar to the results observed for hierarchical clustering methods and for projection in two-dimensional space, the formation of groups with grouping methods by optimization showed variations when using different coefficients. We believe that the results confirm the influence of coefficients in studies of genetic diversity, showing the need to use criteria and standards for selecting appropriate methods for genetic studies of the genus Croton. PMID- 25117314 TI - Implications of microRNA-197 downregulated expression in esophageal cancer with poor prognosis. AB - The aim of this study was to investigate the significance of the microRNA miR-197 expression level in relation to clinicopathological factors and prognoses of esophageal cancer (EC). MicroRNA was extracted using the Taqman((r)) MicroRNA Assay from 46 EC patients at the same tumor node metastasis (TNM) stage, but with different prognoses, who underwent surgery. Paracancerous normal tissues were used as controls. The correlation between miR-197 expression and clinicopathologic features was analyzed, and the significance of miR-197 as a prognostic factor and its relationship with survival was determined. miR-197 expression was lower in patients with poor prognosis than in those with good prognosis (P < 0.05). Kaplan-Meier analysis results showed that the miR-197 expression level is significantly correlated with survival time (P = 0.030), and that patients with higher expression of miR-197 had longer survival times. Cox multi-factor model analysis showed that patient prognosis (P = 0.001), tumor length (P = 0.010) and expression (P = 0.042), and survival time were significantly correlated, with corresponding risks of 9.183, 2.318, and 1.925, respectively. This study supports a role of miR-197 as an anti-oncogene and a biomarker for EC and its relationship with other prognostic factors and survival. PMID- 25117315 TI - A potential protective role for thiamine in glucose-driven oxidative stress. AB - The relationship between glucose repression and the oxidative stress response was investigated in Schizosaccharomyces pombe wild type cells (972h(-)) and glucose repression resistant mutant type cells (ird11). We aimed to reveal the mechanism of simultaneous resistance to glucose repression and oxidative stress in ird11 mutants. Compared to the wild type, the expression of the sty1 gene was not altered in the ird11 mutant under normal growth conditions, but decreased after exposure to H2O2. This effect was clearly explained by the immunoblotting results, which showed elevated levels of a much more stable phosphorylated form of Sty1 mitogen-activated protein kinase in the ird11 mutant. Increased ght3 gene expression levels were also found, which may play a role in protecting the ird11 mutant from the deleterious effects of oxidative stress. In addition, decreased expression levels of glycolytic enzyme enolase- and thiamine synthesis/transport related genes were detected. This might have resulted from the flux redirection toward mitochondrial respiration, which would enhance NADPH generation to prevent the high reactive oxygen species accumulation that is generated by respiration. Some evidence supported a flux shift toward fermentation as well as respiration. We conclude that a defect in the glucose-sensing signaling pathway in ird11 mutants likely causes erroneous low glucose-sensing signaling and high ATP production. This most likely occurs because high glucose availability in the medium induces an impairment in the respiratory chain and fermentation balance in these cells, which might explain the glucose repression and oxidative stress resistance in ird11 compared to the wild type. PMID- 25117316 TI - Diagnosis of lymph node micrometastasis at the pN0 stage of lung adenocarcinoma using a combination of markers. AB - This study aimed to detect micrometastatic tumor cells in the lymph nodes of patients with pN0 lung adenocarcinoma using a combination of thyroid transcription factor-1 (TTF-1) expression and cytokeratin 7 (CK7) expression and to investigate the association of lymph node micrometastasis with the clinicopathological characteristics of patients with lung adenocarcinoma. A total of 54 patients with pN0 lung adenocarcinoma and whose primary tumors were positive for both TTF-1 and CK7 expression were included in this study. In total, 893 lymph nodes were obtained from these 54 patients and were analyzed for micrometastasis by immunohistochemical staining with anti-CK7 and anti-TTF-1 antibodies. CK7- and TTF-1-positive cells were found in the lymph nodes of 9 (16.7%) of 54 patients, and 21 (2.4%) of 893 lymph nodes exhibited positivity for these factors. No cells positive for both CK7 and TTF-1 were detected in the 5 lymph nodes obtained from patients with benign lung tumors. Lymph node micrometastasis was found to be associated with the differentiation grade and primary tumor position (P < 0.05). The detection of lymph node micrometastasis by a combination of CK7 and TTF-1 immunohistochemical staining provides a more accurate assessment of tumor staging for pN0 lung adenocarcinoma. PMID- 25117317 TI - Development and characterization of microsatellite loci for Tabebuia cassinoides (Bignoniaceae). AB - Tabebuia cassinoides (Lam.) DC., popularly known as caxeta, is a tree species that belongs to the plant family Bignoniaceae. This species is endemic to the Brazilian Atlantic Forest and is widely exploited commercially. To date, little is known about its genetic structure, preventing the establishment of adequate management plans for this taxon. The objective of this study was to construct a microsatellite-enriched genomic library for T. cassinoides to select polymorphic loci, and standardize polymerase chain reaction amplification conditions. Of the 15 loci examined, 5 were polymorphic. The number of alleles per locus ranged from 2 to 8, with a mean of 4.4. The microsatellite loci described here represent the basis for detailed population genetic studies of this species, which will greatly contribute for the development of better conservation strategies for this taxon. PMID- 25117318 TI - Effects of phenylalanine on reproductive performance and teratogenesis in mice. AB - We evaluated the effects of phenylalanine on reproductive performance and teratogenesis in mice, as well as we assessed its protective effect in mice treated with an acute dose of cyclophosphamide. Animals were divided into 6 experimental groups (females N = 15/group, males N = 5/group): G1, the negative control group, phosphate-buffered saline; G2, the positive control group, 35 mg cyclophosphamide/kg body weight (b.w.); G3 and G4 received phenylalanine at doses of 150 and 300 mg/ kg b.w., respectively; G5 and G6 received phenylalanine at doses of 150 and 300 mg/kg b.w. co-administered with cyclophosphamide at a dose of 35 mg/kg b.w., respectively. Pregnant mice received phenylalanine from 8-12 days of pregnancy and cyclophosphamide on the 10th day of treatment or the respective vehicles. In animals treated with cyclophosphamide, offspring fetal weight significantly decreased. The G5 and G6 groups, which received cyclophosphamide co-administered with phenylalanine, showed a smaller reduction in weight. Based on this analysis, the offspring from groups G2, G5, and G6 showed low weight due to pregnancy age. Moreover, at the doses used, phenylalanine did not interfere with embryo-fetal development. However, further studies are necessary to increase the understanding of the effects of phenylalanine on mouse reproductive performance and teratogenesis. PMID- 25117319 TI - Identification of complete linkage disequilibrium in the DSG4 gene and its association with wool length and crimp in Chinese indigenous sheep. AB - The desmoglein 4 (DSG4) gene is a potential candidate in the search for genes that may affect wool traits, because of its function. This study aimed to screen for polymorphisms in partial exon 16 and 3?UTR of the sheep desmoglein 4 DSG4 gene, and to test its possible association with wool length and crimp associated with fur. Overall, 326 sheep were scanned via single-strand conformational polymorphism assay, through three pairs of primers. The breeds included Tan, Han, and TanxHan from China, Polled Dorset from Australia, and Suffolk from Britain genotypes AA, BB, and AB for primer2 and genotypes DD, EE, and DE for primer3 were detected in native breeds. Six SNPs and 3-bp insertion/deletions were found in exon 16, of which 4 lead to amino acid substitutions. In addition, 1 SNP was found in 3?UTR. The DSG4 genotype was found to be strongly associated with all wool traits that were considered in this study (P < 0.01). Sheep with the genotype MM had a higher least square mean compared to sheep with the genotype WW or WM with respect to birth scapular wool length (P < 0.01), crimp number of birth scapular wool crimp (P < 0.01), crimp number of weaning scapular wool crimp (P < 0.01), and crimp number of weaning rump wool crimp (P < 0.01, P < 0.05). In conclusion, our study is the first to demonstrate that the DSG4 gene may be a candidate, or major gene, which influences important wool traits. PMID- 25117320 TI - Soybean rust resistance sources and inheritance in the common bean (Phaseolus vulgaris L.). AB - Soybean rust (SBR), caused by the fungus Phakopsora pachyrhizi, has been reported in common bean (Phaseolus vulgaris L.) cultivars and elite lines that were infected under controlled and natural field conditions in South Africa, the United States, Argentina, and Brazil. Although SBR is currently not a top priority problem for the common bean crop, many bean breeders are concerned about this disease because of the high severity and virulence diversity of P. pachyrhizi and its broad host range. In this study, a set of 44 P. vulgaris genotypes were tested for resistance to P. pachyrhizi; these genotypes included resistance sources to several fungal common bean diseases, carioca-, black- and red-seeded Brazilian cultivars, and elite lines that were developed by the main common bean breeding programs in Brazil. Twenty-four SBR resistance sources were identified. They presented the reddish-brown (RB) lesion type, characterizing resistance reactions. In addition to the RB lesion type, the PI181996 line presented the lowest disease severity mean score, considering its associated standard error value. For this reason, it was crossed with susceptible lines to study the inheritance of resistance. The results support the hypothesis that resistance to SBR in PI181996 is monogenic and dominant. We propose that this SBR resistance gene, the first to be identified and characterized in common bean, might be designated as Pkp-1. PMID- 25117321 TI - CYP1A2 polymorphism in Chinese patients with acute liver injury induced by Polygonum multiflorum. AB - The objective of this study was to evaluate the genotype and allelic frequencies of CYP1A2 in Chinese patients with acute liver injury induced by Polygonum multiflorum. We examined the clinical mechanism of acute liver injury induced by P. multiflorum. According to the diagnostic criteria for drug-induced liver injury (DILI), 43 cases of P. multiflorum-induced liver injury admitted to the First Affiliated Hospital, Zhejiang University were identified between January 2008 and December 2012. An additional 43 control subjects were also chosen. Several alleles, including 1C, 1F, 2, 7, 9, and 11 of CYP1A2 were amplified from genomic DNA and sequenced. We used the chi-square test to determine whether CYP1A2 allele polymorphisms are associated with acute liver injury induced by P. multiflorum. The frequency of the CYP1A2 1C allele was 46.5% in P. multiflorum induced DILI patients, which was significantly different from the frequency of 27.9% observed in healthy subjects. The frequency of the CYP1A2 1F allele was 63.9% in P. multiflorum-induced DILI patients, compared to 57.0% in healthy controls; the difference was not significant. The allelic frequencies of CYP1A2 2, CYP1A2 7, CYP1A2 9, and CYP1A2 11 were too low to be detected. The frequency of the CYP1A2 1C mutation in Chinese patients with P. multiflorum-induced acute liver injury differed from that in healthy Chinese people, indicating that CYP1A2 1C is probably related to metabolism of P. multiflorum, which is followed by acute liver injury. PMID- 25117322 TI - Bovine papillomavirus in beef cattle: first description of BPV-12 and putative type BAPV8 in Brazil. AB - Bovine papillomavirus (BPV) is an oncogenic virus associated with benign and malignant lesions, which result in notable economic losses. Peripheral blood samples and cutaneous papillomas were obtained from four adult beef cattle. Viral molecular identification was performed using specific primers for BPV-1, -2 and 4 in blood diagnosis and FAP59/FAP64 for skin papillomas. Histopathologic examination was done as a complementary and differential diagnosis. The fragments were purified, sequenced, and compared using BLASTn. The blood diagnosis showed the presence of BPV-2 and the analysis of cutaneous papillomas showed the presence of BPV-4, a new putative virus type BAPV8, and BPV-12, revealing for the first time the presence of BPV-12 and the putative type BAPV8 in beef cattle in Brazil. The sequences were deposited in the GenBank. Histopathology revealed acanthosis, hyperkeratosis, and koilocytosis in all samples analyzed. The presence of BAPV8 and BPV-12 in Brazil emphasizes the ubiquitous dissemination of BPVs in the herds of Brazil. PMID- 25117323 TI - Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital teratoma, caused by a PTCH1 frameshift mutation. AB - Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients. PMID- 25117324 TI - Agronomic performance of arabica coffee genotypes in northwest Rio de Janeiro State. AB - Considering the productive potential of arabica coffee in the Rio de Janeiro State and the shortage of breeding programs for this species in the state, this study aimed to evaluate the vegetative and productive characteristics of 25 arabica coffee genotypes to indicate 1 or more varieties for the northwest Rio de Janeiro region. The experiment was in Varre e Sai, RJ, Brazil, and plants were planted in 2007 with a spacing of 2.5 x 0.8 m. Five plots were used, consisting of 8 plants per plot to measure vegetative growth, height, stem diameter, and plagiotropic branch number characteristics and productivity in the biennia 2009/2010 and 2011/2012. The classification by sieve was performed at harvest in 2011. The variables were subjected to analysis of variance and means grouped by the Scott Knott test at 5% probability, and the productivity was subjected to joint analysis of variance. Pearson's correlation coefficients between growth and productivity variables were estimated. The best genotypes were Catucai Amarelo 2 SL, Catigua MG 02, Acaua, Palma II, Sabia 398, IPR 103, IPR 100, Catucai Amarelo 24/137, and Catucai Amarelo 20/15. PMID- 25117325 TI - Construction and identification of pIRES2-NGF-VEGF165 bicistronic eukaryotic expression vector. AB - We used a simple and efficient method to construct the bicistronic eukaryotic expression vector pIRES2-NGF-VEGF165. The nerve growth factor (NGF) gene was obtained from the genomic DNA of human peripheral blood mononuclear cells by polymerase chain reaction. The NGF cDNA fragment was inserted into the multiple cloning sites of the pIRES2-EGFP vector to generate the bicistronic eukaryotic expression plasmid pIRES2-NGF-EGFP. The vascular endothelial growth factor 165 (VEGF165) gene was obtained from the pIRES2-VEGF165-EGFP plasmid by polymerase chain reaction. Next, the VEGF165 cDNA fragment was cloned into pIRES2-NGF-EGFP in place of enhanced green fluorescent protein creating the plasmid pIRES2-NGF VEGF165. pIRES2-NGF-VEGF165 was transfected into HEK293 cells and reverse transcription-polymerase chain reaction and Western blot analysis were used to test the co-expression of double genes. The NGF and VEGF165 genes were cloned and the DNA was sequenced, which revealed that NGF and VEGF165 were consistent with the sequence recorded in GenBank. Restriction analysis showed that the NGF and VEGF165 genes were inserted into the expression vector pIRES2-EGFP. Transfection of pIRES2-NGF-VEGF165 into HEK293 cells resulted in expression of the double gene at the mRNA and protein levels. The NGF and VEGF165 coexpression plasmid provides a novel expression system, enabling further study of the functions of the NGF and VEGF165 genes. PMID- 25117326 TI - Bias toward a 1:1 ratio in primer-introduced restriction analysis PCR: mechanism and minimization. AB - Primer-introduced restriction analysis is widely used in molecular genetics. However, several studies have reported inconsistent data regarding sequencing, mainly among heterozygous samples. This discrepancy may be related to the bias towards a 1:1 ratio typically observed in heterozygous digestion products. In this study, we investigated the mechanism and minimization of this observed bias. Three mismatched polymerase chain reaction (PCR) models were analyzed by testing different PCR conditions and reaction mixtures. For EPHX1 gene rs1051740 single nucleotide polymorphism PCR, DNA concentration, denaturation and elongation time, annealing temperature, and cycle number significantly influenced product ratios. For SERPINA1 gene PIMmalton deletion (DeltaPhe52) and CHRNA3 gene rs1051730 single-nucleotide polymorphism PCRs, significant bias fluctuations were observed only for the annealing temperature and cycle number conditions. The relevance of these results to the amplification efficiency parameter is discussed. Rather than reducing the observed bias, our data provide evidence of a counterbalance for preferential amplification, depending on cycle number, annealing temperature, and amplification efficiency alteration. Our results are relevant for application to primer-introduced restriction analysis PCR assays. PMID- 25117327 TI - Pulmonary hypertension in patients with stage 1-3 chronic kidney disease. AB - Pulmonary hypertension (PH) secondary to chronic kidney disease (CKD) is common, but in stages 1-3 CKD patients, it remains unclear. We sought to evaluate the prevalence of PH and elucidate the possible pathogenesis in Chinese patients with early stage kidney disease. Doppler-estimated pulmonary systolic artery pressure (PASP) was measured in 101 CKD patients with glomerular filtration rate (GFR) >= 60 mL/min/1.73 m(2) and 27 CKD patients with GFR < 60 mL/min/1.73 m(2). Echocardiographic parameters, plasma brain natriuretic peptide (BNP), and baseline characteristics of patients were recorded. PH was defined as a PASP >= 35 mmHg. PH prevalence was 23.76% (24/101) in GFR >= 60 mL/min/1.73 m(2) group and 48.15% (13/27) in GFR < 60 mL/min/1.73 m(2) group, P < 0.05. Mean lnBNP was 4.93 +/- 1.60 pg/mL in 37 cases with PH and 2.89 +/- 1.29 pg/mL in those without, P < 0.01. Left atrial diameter (LA) showed deviation between patients with (43.94 +/- 5.81 mm) and without PH (37.76 +/- 7.48 mm), P < 0.01. GFR declined significantly in PH group (44.10 +/- 22.90 mL/min/1.73 m(2)) compared to non-PH group (75.59 +/- 31.62 mL/min/1.73 m(2)), P < 0.01. lnBNP, LA and GFR were independent determinants (r = 0.651, 0.595, -0.488, P < 0.01) of PASP. PH is prevalent among stage 1-3 CKD patients in China. Doppler-estimated PASP is strongly associated with lnBNP, enlarged LA and GFR. Monitoring PASP, plasma BNP and evaluation renal function may help to detect and prevent severe PH in CKD. PMID- 25117328 TI - Outbreaks and genetic diversity of Francisella noatunensis subsp orientalis isolated from farm-raised Nile tilapia (Oreochromis niloticus) in Brazil. AB - Francisella noatunensis subsp orientalis (FNO) is an emerging pathogen of warm water tilapia in a number of different countries. The disease caused by this bacterium in fish is characterized by a systemic granulomatous infection that causes high mortality rates during outbreaks. FNO has been previously described in Asia, Europe, and Central and North America. Its occurrence in South America has never been described. Since 2012, outbreaks of a granulomatous disease have been recorded in cage farms of Nile tilapia (Oreochromis niloticus L.) in Brazil. The current study aimed to identify the etiologic agent of recent francisellosis outbreaks at Brazilian tilapia farms, and to characterize the genetic diversity of the pathogen from farms with distinct geographic origins and without epidemiological connections. Bacteriological analysis of 44 diseased Nile tilapia collected from five cage farms in Brazil was performed during 2012 and 2013. The farms were in different locations and had no recent history of animal or biological material transport between each other. Sixty-two FNO isolates were identified on the basis of FNO-specific qPCR. The main predisposing factors for the occurrence of outbreaks on Brazilian farms were lower water temperature (<22 degrees C) and life stage of fish, affecting mainly fry, fingerlings and young adults (live weight <100 g). The genetic diversity of the Brazilian FNO isolates was evaluated using repetitive extragenic palindromic-PCR. The isolates from different origins were shown to be clonally related. This is the first report of the occurrence and genetic diversity of FNO in South America. PMID- 25117329 TI - Pharmacogenomics: accessing important alleles by imputation from commercial genome-wide SNP arrays. AB - Personalized medicine is becoming a medical reality, as important genotype phenotype relationships are being unraveled. The availability of pharmacogenomic data is a key element of individualized care. In this study, we explored genotype imputation as a means to infer important pharmacogenomic alleles from a regular commercially available genome-wide SNP array. Using these arrays as a starting point can reduce testing costs, increasing access to these pharmacogenomic data and still retain a larger amount of genome-wide information. IMPUTE2 and MaCH Admix were used to perform genotype imputation with a dense reference panel from 1000 Genomes data. We were able to correctly infer genotypes for the warfarin related loci VKORC1 and CYP2C9 alleles 2, 3, 5, and 11 and also clopidogrel related CYP2C19 alleles 2 and 17 for a small sample of Brazilian individuals, as well as for HapMap samples. The success of an imputation approach in admixed samples using publicly available reference panels can encourage further imputation initiatives in those populations. PMID- 25117330 TI - Ranking of Nellore animals in cattle championships: genetic parameters and correlations with production traits. AB - Records of 17,141 Nellore cattle participating in cattle championships, born from 1994-2009, were used to estimate genetic parameters between animal rank in cattle championships, evaluated from weaning to 36 months of age as repeated traits, and growth, fertility, and carcass traits, evaluated at 365 days of age as single traits. Two traits were defined for animal rank in cattle championships: value 1 was attributed to animals ranked from 1st to 3rd place within the age category, and value 0 was assigned to the remaining animals (TOP3). Value 1 was attributed to animals ranked from 1st to 5th place within the age category and value 0 was assigned to the remaining animals (TOP5). The (co)variance components were estimated based on Bayesian inference under a 2-trait threshold-linear animal model. The posterior means of heritability estimated for TOP3 and TOP5 were 0.182 +/- 0.010 and 0.260 +/- 0.012, respectively, and their repeatabilities were 0.341 +/- 0.007 and 0.400 +/- 0.007, respectively. High-ranking animals generally presented higher breeding values for body weight, height, body length, and heart girth. The phenotypic correlations indicate that judges of cattle championships primarily rank animals based on weight and heart girth. PMID- 25117331 TI - HIF1A gene Pro582Ser polymorphism and susceptibility to digestive tract cancers: a meta-analysis of case-control studies. AB - Many existing studies have demonstrated that common polymorphisms in the hypoxia inducible factor-1alpha (HIF-1A) may contribute to the development of digestive tract cancers, but individually published studies showed inconclusive results. This meta-analysis aimed to derive a precise estimation of the relationships between HIF1A Pro582Ser polymorphism and the risk of digestive tract cancers. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through May 1, 2013. Meta-analysis was performed using the STATA 12.0 software. We assessed 6 case-control studies that included a total of 911 digestive tract cancer patients and 2774 healthy controls. Our meta-analysis indicated that HIF1A Pro582Ser polymorphism was associated with an increased risk of digestive tract cancer. Subgroup analysis by ethnicity suggested that HIF1A Pro582Ser polymorphism might increase an individual's susceptibility to digestive tract cancer in Asian populations. However, similar association was not observed in Caucasian populations. In conclusion, our findings suggest that HIF1A Pro582Ser polymorphism may contribute to the risk of digestive tract cancers, especially in Asian populations. PMID- 25117332 TI - Fibroin protein/chitosan scaffolds and bone marrow mesenchymal stem cells culture in vitro. AB - A previous experiment demonstrated that fibroin protein and chitosan mixed in proper proportion presented good physical and chemical properties and biological characteristics, which can make up for their respective disadvantages. To observe the growth of bone marrow mesenchymal stem cells (BMSCs) on these fibroin protein/chitosan 3D scaffolds, induced rabbit BMSCs were seeded on fibroin protein/chitosan scaffolds. The cell adhesion rate was measured, and cell growth was observed under an inverted microscope and a scanning electron microscope. The cell adhesion rate increased with time. The inverted microscope observations showed that the cells on fibroin protein/chitosan scaffolds could not be seen clearly. As time passed, the number of cells around the stent increased and some cells stretched inside the scaffolds. Electron microscopy showed active cell growth and normal proliferation, and the granular and filamentous matrix substances could be seen around cells. The microfilaments of cell and scaffold materials were tightly connected. The cells not only grew on the surface of the adherent material, but also stretched inside of the materials. These results indicated that the fibroin protein/ chitosan mixed scaffolds have good biocompatibility. PMID- 25117333 TI - Association study of plasma NT-proBNP levels and severity of acute coronary syndrome. AB - The aim of this study was to investigate the N-terminal brain natriuretic peptide precursor (NT-proBNP) levels in the peripheral blood of patients with acute coronary syndrome (ACS) and to provide the basis for its application in the early diagnosis of ACS. A total of 440 patients admitted to the hospital for examination and treatment were enrolled, including 330 patients with ACS and 110 cases in the control group. Routine blood examination and determination of NT proBNP in all subjects were conducted immediately at the time of admission to analyze the difference in plasma NT-proBNP between the two groups. The plasma NT proBNP levels in ACS were significantly higher (P < 0.01) and were associated with the severity of coronary lesions. The present study indicated that the plasma NT-proBNP level in ACS patients is significantly increased and has a potential value in the early diagnosis of ACS. PMID- 25117334 TI - Alteration of coenzyme specificity of malate dehydrogenase from Streptomyces coelicolor A3(2) by site-directed mutagenesis. AB - We describe here for the first time the alteration of coenzyme specificity of malate dehydrogenase (MDH) from Streptomyces coelicolor A3(2) (ScMDH). In the present study, we replaced four amino acid residues in the Rossmann fold (betaB alphaC) region of NADH-dependent ScMDH by site-directed mutagenesis with those of NADPH-dependent MDH (Glu42Gly, Ile43Ser, Pro45Arg, and Ala46Ser). The coenzyme specificity of the mutant enzyme (ScMDH-T4) was examined. Coenzyme specificity of ScMDH-T4 was shifted 2231.3-fold toward NADPH using kcat/Km(coenzyme) as the measurement of coenzyme specificity. Accordingly, the effect of the replacements on coenzyme specificity is discussed. Our work provides further insight into the coenzyme specificity of ScMDH. PMID- 25117335 TI - Influence of hepatic ischemia-reperfusion on postoperative spatial cognitive function in mice. AB - The aim of this study was to investigate the effects of partial hepatic ischemia/reperfusion (I/R) on postoperative cognitive function in mice. One hundred Kunming mice were randomized into control group (N = 20), sham group (N = 20) and I/R group (N = 60), which was equally divided into 3 subgroups according to the ischemia time (20, 30 and 40 min). Half of the mice in each group underwent a passive avoidance test on the 4th day, and the other underwent the test on the 18th day, which lasted for 6 days before euthanasia for analysis of brain pathology and immunohistochemistry for ChAT. The passive avoidance test showed that there was no significance in the incubation period and number of errors between the control and sham group, but there was a longer incubation period and more errors in the I/R group than control group; at G2, there was no significance between all groups. Hematoxylin-eosin staining of the hippocampus showed that at G1, there was no obvious change in hippocampal neurons in structure and arrangement except for IR/40 min; at G2, there was no significance between all groups. Immunohistochemistry of hippocampus for ChAT showed the following: at G1, there was no significance in average optical density of CA3 area between control and sham group, but optical density was significantly lower in I/R groups with I/R 40 min showing the lowest; at G2, there was no significance between all groups. Pentobarbital has no effect on cognitive function, but hepatic partial ischemia and reperfusion injury does and could become worse over time. PMID- 25117336 TI - Analysis of genetic relationships and identification of lily cultivars based on inter-simple sequence repeat markers. AB - Inter-simple sequence repeat (ISSR) markers were used to discriminate 62 lily cultivars of 5 hybrid series. Eight ISSR primers generated 104 bands in total, which all showed 100% polymorphism, and an average of 13 bands were amplified by each primer. Two software packages, POPGENE 1.32 and NTSYSpc 2.1, were used to analyze the data matrix. Our results showed that the observed number of alleles (NA), effective number of alleles (NE), Nei's genetic diversity (H), and Shannon's information index (I) were 1.9630, 1.4179, 0.2606, and 0.4080, respectively. The highest genetic similarity (0.9601) was observed between the Oriental x Trumpet and Oriental lilies, which indicated that the two hybrids had a close genetic relationship. An unweighted pair-group method with arithmetic means dendrogram showed that the 62 lily cultivars clustered into two discrete groups. The first group included the Oriental and OT cultivars, while the Asiatic, LA, and Longiflorum lilies were placed in the second cluster. The distribution of individuals in the principal component analysis was consistent with the clustering of the dendrogram. Fingerprints of all lily cultivars built from 8 primers could be separated completely. This study confirmed the effect and efficiency of ISSR identification in lily cultivars. PMID- 25117337 TI - Optimization of chloroplast microsatellite PCR conditions and primer screening for endangered Rheum officinale, Rheum palmatum, and Rheum tanguticum. AB - Chloroplast microsatellite primers were developed in order to provide more population genetic information of endangered Rheum officinale, R. palmatum, and R. tanguticum for conservation. The dried roots and rhizomes of these plants are important in traditional Chinese medicine. The results showed that the optimum concentrations of Mg(2+), Taq DNA polymerase, dNTPs, template DNA, and primers in a 25-MUL reaction system were 2.0 mM, 1.0 U, 0.10 mM, 20 ng, and 0.8 MUM, respectively. Fourteen of 53 primer combinations were chosen for their high clarity and repetition in three species, and their annealing temperatures ranged from 56 to 58 degrees C. These primers and the optimized polymerase chain reaction system may provide a tool for understanding the demography and genetic variation of these endangered plants. PMID- 25117339 TI - Sequence analysis of the PIP5K locus in Eimeria maxima provides further evidence for eimerian genome plasticity and segmental organization. AB - Commercial flocks infected by Eimeria species parasites, including Eimeria maxima, have an increased risk of developing clinical or subclinical coccidiosis; an intestinal enteritis associated with increased mortality rates in poultry. Currently, infection control is largely based on chemotherapy or live vaccines; however, drug resistance is common and vaccines are relatively expensive. The development of new cost-effective intervention measures will benefit from unraveling the complex genetic mechanisms that underlie host-parasite interactions, including the identification and characterization of genes encoding proteins such as phosphatidylinositol 4-phosphate 5-kinase (PIP5K). We previously identified a PIP5K coding sequence within the E. maxima genome. In this study, we analyzed two bacterial artificial chromosome clones presenting a ~145-kb E. maxima (Weybridge strain) genomic region spanning the PIP5K gene locus. Sequence analysis revealed that ~95% of the simple sequence repeats detected were located within regions comparable to the previously described feature-rich segments of the Eimeria tenella genome. Comparative sequence analysis with the orthologous E. maxima (Houghton strain) region revealed a moderate level of conserved synteny. Unique segmental organizations and telomere-like repeats were also observed in both genomes. A number of incomplete transposable elements were detected and further scrutiny of these elements in both orthologous segments revealed interesting nesting events, which may play a role in facilitating genome plasticity in E. maxima. The current analysis provides more detailed information about the genome organization of E. maxima and may help to reveal genotypic differences that are important for expression of traits related to pathogenicity and virulence. PMID- 25117338 TI - Effects of acrylonitrile on the pathological morphology and apoptosis of neurons in rats. AB - This study aimed to evaluate the effects of acrylonitrile (ACN) on neuronal morphology and apoptosis in rats. An ACN solution was administered to Wistar rats by gavage at doses of 0, 5, 10, or 20 mg/kg, 5 days a week for 13 weeks. The morphology of neurons and the presence of apoptosis was examined by light and electron microscope, DNA electrophoresis, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Significant vacuolation and the widening of the interspaces around blood vessels were observed in the groups that received the highest dose. Disordered myelin sheaths, malformed neuronal nuclei, and chromatin condensation at the periphery of the nucleus that formed crescents were also observed in the treated rats. The number of apoptotic neurons was significantly decreased (P < 0.05) in the treated groups (5 mg/kg group: 1.5 +/- 1.22 apoptotic neurons/slide; 10 mg/kg group: 2.5 +/- 1.05 apoptotic neurons/slide; 20 mg/kg group: 2.34 +/- 1.21 apoptotic neurons/slide) compared to the control group (4.5 +/- 1.52 apoptotic neurons/slide). The number of Bcl-2-positive neurons and the levels of staining were increased in the treated rats compared to those of the control group. These results suggested that ACN may induce serious morphological changes in rat neurons and inhibit neuronal apoptosis in rats. PMID- 25117340 TI - Evaluation of genetic similarity between accessions of Pityrocarpa moniliformis (angico-de-bezerro) using RAPD markers. AB - Pityrocarpa moniliformis (Benth.) Luckow and Jobson, commonly known as angico-de bezerro, is a forage legume that occurs naturally in the Caatinga of northeastern Brazil. This fast growing, vigorous, melliferous tree is well adapted to arid terrains and its branches and leaves possess high nutritional value. However, the scarcity of information regarding genetic variability within the species limits its possible exploitation as an animal forage. The aim of the study was to evaluate the genetic similarities of ten accessions of P. moniliformis available in the active germplasm collection of Embrapa Meio-Norte, using the RAPD markers to select those most suitable for cultivation and/or plant breeding. Polymerase chain reaction using ten selected RAPD primers generated 110 amplified loci, 106 (96.4%) of which were polymorphic. Primers A10 and M06 produced the largest number of polymorphic loci (18 and 13 bands, respectively), while primers B18 and K15 generated the smallest number (7 bands each). The dendrogram, constructed using the Jaccard coefficients and considering a cut-off point of 0.41 allowed the separation of the ten accessions into four genotypic groups. The highest genetic similarity coefficient (0.56) was observed between group I accessions BGFAB6 and BGFAB9 and BGFAB 7 and BGFAB 8, while the lowest coefficient (0.11) was observed between accessions BGFAB3 (group IV) and BGFAB10 (group III). The results revealed that genetic variability is present in the accessions of P. moniliformis. PMID- 25117341 TI - RAPD analysis of the genetic diversity among accessions of Fabaceous forages (Poincianella spp) from the Caatinga. AB - Among members of the Fabaceae family, native to the Brazilian Caatinga, the species Poincianella pyramidalis and P. bracteosa exhibit particular potential as forage for cattle, sheep and goats. With the aim of establishing genetic relationships within Poincianella, random amplified polymorphic DNA analysis was performed on eight accessions of P. pyramidalis and two accessions of P. bracteosa, originating from the semiarid zone of the state of Piaui, northeastern Brazil, and present in the germplasm bank of Embrapa Meio Norte (Teresina, Piaui, Brazil). Amplification reactions using 11 selected arbitrary sequence primers generated 167 fragments with an overall polymorphism of 70.38%. Five monomorphic loci were generated exclusively in P. pyramidalis accessions, while three unique monomorphic loci were associated with P. bracteosa, and these represented potential species-specific markers. The similarity coefficients between Poincianella accessions were low (mean value 0.59) but with a wide variation (range 0.443 to 0.748). The similarity matrix and the dendrogram constructed using the unweighted pair group method allowed the separation of Poincianella accessions into two major clusters represented by the two distinct species, while the accessions of P. pyramidalis could be separated further into three subgroups. The high level of genetic diversity detected in the genus Poincianella could be used in future breeding programs to produce enhanced cultivars, although the variability could be better exploited if more specimens were collected from other locations within the semiarid region of northeastern Brazil. PMID- 25117342 TI - Genetic parameters for earnings in Quarter Horse. AB - In this study, we estimated the heritability (h(2)) of earnings in the Quarter Horse in order to evaluate the inclusion of this trait in breeding programs. Records from 14,754 races of 2443 horses from 1978-2009 were provided by Sorocaba Hippodrome, Sao Paulo, Brazil. All ancestors of the registered horses were included in the pedigree file until the 4th generation. Log-transformed performance measures (LPM) were analyzed for animals aged 2, 3, and 4 years and during their entire career. The h(2) estimates were obtained using a multi-trait model and Gibbs sampling that included the effects of sex, year of race, and animal in all analyses. Five analyses were performed: 1 in which LPM was divided by the number of prizes, 1 in which LPM was divided by the number of race starts, and 3 analyses that included the number of prizes, number of race starts, and both (LPM_cNPS) as covariates. Analysis was performed with and without inclusion of the maternal effect. Models were compared based on the deviance information criterion and LPM_cNPS including maternal effects was found to be the best model. The h(2) estimates and standard deviation obtained using model LPM_cNPS were 0.19 +/- 0.08, 0.21 +/- 0.08, 0.22 +/- 0.09, and 0.21 +/- 0.07 for earnings at 2, 3, and 4 years of age and total career, respectively. Our analyses indicate that earnings are subject to selection and can be included in breeding programs to improve the racing performance of Quarter Horses. PMID- 25117343 TI - Complete mitochondrial genome of a natural triploid crucian carp mutant, Carassius auratus var. pingxiangnensis, and phylogenetic analysis of different ploidies in crucian carp. AB - Carassius auratus var. pingxiangnensis is a natural triploid crucian carp mutant. In order to understand its placement and genetic background at the gene level, the characteristics of mitochondrial DNA sequences and phylogenetic relationship were examined. The results showed that the mitochondrial DNA is a circular double stranded DNA molecule that is 16,576 bp in length with 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a non-coding control region. Mitochondrial genes overlapped by a total of 40 bp in 11 different locations from 1 to 14 bp. The base composition of the C. auratus mitogenome was estimated to be 29.70% A, 26.74% C, 15.35% G, and 28.21% T. The central conserved blocks and the conserved blocks were compared and were similar among C. auratus var. pingxiangnensis and six other cyprinids with different ploidies. The origin of light strand replication was similar to that of other vertebrates; it was 33 bp, but the characteristic sequence motif 5?-GCCGG-3? at the base of the stem within tRNA(Cys) was mutated to 5?-GGCGG- 3?. Our phylogenetic analysis based on whole mitogenome sequences indicated that C. auratus var. pingxiangnensis was clustered with C. auratus and then sister-grouped with Carassius gibelio. The systemic developmental tree of crucian carp with different chromosome ploidies showed that diploid C. auratus auratus was clustered with triploid C. auratus auratus, sister grouped with tetraploid C. auratus auratus, and clustered with other diploid, triploid, and tetraploid C. auratus. PMID- 25117344 TI - Transcription factor 7-like 2 polymorphisms and diabetic retinopathy: a systematic review. AB - The global prevalence of type 2 diabetes mellitus (T2DM) has increased, as well as complications including diabetic retinopathy. Polymorphisms in transcription factor 7-like 2 (TCF7L2) have been associated with T2DM, with the strongest association attributed to the single-nucleotide polymorphism rs7903146. In this review, we searched the current literature to determine whether an association exists between TCF7L2 polymorphisms rs7903146 with diabetic retinopathy. A systematic search was performed of EMBASE, PubMed, and Scopus using the following search terms: diabetic, retinopathy, polymorphism, genetic, transcription factor 7-like 2, TCF7L2. A manual search was also performed. There was no language or study design restriction. Three full articles and one abstract were reviewed. All studies were retrospective case-control studies that compared the frequency of the wild-type CC genotype and genotypes with the risk T allele. None of the studies found a statistically significant odds ratio. While the number of studies examined was small, this review suggests that there is no risk of diabetic retinopathy among individuals with the TCF7L2 polymorphisms rs7903146; however, the polymorphism may play a small role in diabetic retinopathy. Future prospective studies and trials involving diverse ethnicities that adjust for confounding variables are required to understand the association between TCF7L2 polymorphisms and diabetic retinopathy. PMID- 25117345 TI - Interleukin-1B-31 gene polymorphism in Hakka gastric cancer patients in Guangdong, China. AB - The aim of this study was to examine the interleukin-1B (IL-1B) gene promoter region -31 (IL-1B-31) polymorphism distribution characteristic of Hakka gastric cancer patients in Guangdong Province and to explore its association with gastric cancer. We used the 1:1 case-control method, matrix-assisted laser desorption ionization flight time mass spectrometry, and MassARRAY-IPLEX technology to genotype IL-1B-31 (-31C> T) in 52 Hakka gastric cancer patients and 52 Hakka control subjects in Meizhou. Three genotypes - CT, TT, and CC - of IL-1B-31 were found in the Meizhou Hakka population. Their distribution frequencies in the gastric cancer group were 40.38, 40.38, and 19.23%, respectively, whereas the frequencies in control subjects were 57.69, 17.31, and 25.00%, respectively. The differences in frequency distributions of the genotypes between the 2 groups were statistically significant (chi-square = 6.78, P < 0.05). Subjects with the TT genotype had a higher risk of gastric cancer compared with that in subjects carrying the CT genotype (odds ratio = 2.857, 95% confidence interval = 1.114 7.328). This risk was more apparent in male subjects. IL-1B-31 locus polymorphism may be associated with gastric cancer susceptibility in this population, but additional studies with larger sample size are needed to confirm the conclusions. PMID- 25117346 TI - Large-scale analysis of factors influencing nonalcoholic fatty liver disease and its relationship with liver enzymes. AB - Serum liver enzyme levels are often used effectively for the evaluation of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the associations between serum liver enzyme levels and risks for NAFLD in over 8000 cases in a large-scale analysis. A cross-sectional survey with multiple stages and random samplings was performed from May 2007 to May 2009 on 8102 workers at Tongji University. A questionnaire was given, assessments of physical measurements, plasma glucose, lipid profiles, and liver enzymes were made, and real-time liver ultrasounds conducted. The prevalence of NAFLD in Tongji University was 22.2%. It was higher in males than in females (P = 0.0023). The body mass index, waist-to-hip ratio, serum total triglycerides, serum total cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) values were all higher in the NAFLD group than in the control group. For moderate and severe NAFLD patients, the ALT, AST and GGT values were significantly increased, high density lipoprotein cholesterol was decreased, and drinking much, heavy entertainment and less exercise were more prevalent (P < 0.001). There were strong correlations between serum liver enzyme levels and NAFLD (P < 0.001), with GGT being a more sensitive marker for NAFLD than ALT or AST. ALT and GGT were independent predictors for NAFLD, and GGT was a better predictor than ALT for NAFLD. PMID- 25117347 TI - Different magnitude of resistance to non-depolarizing muscle relaxants in dexamethasone-treated rat diaphragm associated with altered acetylcholine receptor expression. AB - The aim of this study was to investigate the influence of chronic dexamethasone (Dex) administration on rat diaphragm sensitivity to non-depolarizing muscle relaxants (NDMRs) and muscular nicotinic acetylcholine receptor (nAChR) expression, which may help direct future administration of NDMRs. Adult male Sprague-Dawley rats were randomized to receive a daily intraperitoneal injection of Dex (600 MUg/kg body mass) or an equivalent volume of saline (N = 20 in each group) for 14 days. We evaluated isometric twitch tensions of nerve-hemidiaphragm preparations elicited by indirect supramaximal stimulation at 0.1 Hz. Real-time quantitative PCR was performed to determine the mRNA expression of two nAChR subunits (epsilon-subunit and gamma-subunit) in the diaphragm. Dex administration markedly (P < 0.01) increased the 50% twitch depression (IC50) of the three NDMRs. The IC50 ratio, which standardized the magnitudes of the resistance, was the largest for atracurium, with the second largest for vecuronium and the smallest for rocuronium (P < 0.01). The epsilon- and gamma-subunit mRNAs were both upregulated with an increased gamma/epsilon ratio in rats exposed to Dex. The results indicated that chronic Dex administration induces hyposensitivity to NDMRs, the degree of which depends on the kind of neuromuscular blocker, and is associated with increased nAChR expression. PMID- 25117348 TI - RNA interference of leptin receptor in chicken adipocytes. AB - In this study, chicken adipocytes were cultured to evaluate RNA interference by the leptin receptor gene. A small interfering RNA of the leptin receptor gene was synthesized, with a suppression rate of 60% being generated (P < 0.01). After the knockdown of the leptin receptor, the expression levels of certain genes decreased significantly; specifically, peroxisome proliferator-activated receptor gamma, fatty acid synthase, adipose triglyceride lipase, and lipoprotein lipase. In addition, a significant increase in the expression of the adiponectin gene was documented. These results demonstrate that the leptin receptor gene might contribute to lipid metabolism by influencing the expressions of the peroxisome proliferator-activated receptor gamma, fatty acid synthase, adipose triglyceride lipase, lipoprotein lipase, and adiponectin genes. PMID- 25117349 TI - Analysis of transferability of microsatellite primers (SSR) in wild Passiflora species and intraspecific genetic diversity in Passiflora alata. AB - The genus Passiflora L. is the most representative of Passifloraceae, with over 500 known species, among which 150-200 originated from Brazil. In addition to the great commercial importance of this genus for the fruit market, many of the species have exotic flowers with a huge diversity of colors and can thereby be exploited as ornamental plants. This study was aimed at investigating the transferability of microsatellite primers in wild Passiflora species (P. cacao, P. cincinnata, P. glandulosa, P. gibertii, and P. mucronata) and characterizing 29 P. alata accessions using microsatellite primers that were previously developed in a library enriched with microsatellites from P. edulis f. flavicarpa for P. alata. The interspecies cross-amplification rate varied, and P. cacao exhibited the highest rate of amplification, suggesting a greater degree of proximity to P. edulis. The study of intraspecific accessions in P. alata found genetic similarity, with values ranging from 0.47 to 1.00 and an average similarity of 0.74. Hence, this study revealed the intraspecific genetic variability of P. alata in the Universidade Estadual de Santa Cruz's Active Germplasm Bank and will lead to the adoption of mating strategies between accessions; thus making their use more suitable for breeding purposes. PMID- 25117350 TI - Changes in cyclic GMP level and phosphodiesterase activity during follicular development in the rat ovary. AB - Guanosine 3',5'-cyclic monophosphate (cGMP), as a second messenger, plays potential roles in ovarian functions. To elucidate the role of phosphodiesterase (PDE) in cGMP signaling during ovarian follicular development, the present study was conducted to investigate ovarian cGMP level and cGMP-PDE activity by radioimmunoassay (RIA) in postnatal rats, immature rats during gonadotropin primed follicular development, ovulation and luteinization, adult rats during normal estrous cycle, and aged rats that spontaneously developed persistent estrus (PE). All four rat models were confirmed by histological examination of one ovary, and the other ovary was used for RIA. In postnatal rats, cGMP level was high at birth and decreased dramatically by Day 5, and then, it increased maximally at Day 10 and declined at Day 21. However, cGMP-PDE activity did not significantly change during Days 1 to 10, but increased significantly on Day 21. In immature female rats, cGMP level markedly decreased upon treatment with equine chorionic gonadotropin (eCG), while cGMP-PDE activity did not show any significant changes; however, ovarian cGMP level and cGMP-PDE activity increased after injection of an ovulatory dose of human chorionic gonadotropin (hCG) for induction of ovulation and luteinization. In adult rats during normal estrous cycle, cGMP level was high on proestrus and metestrus days, while cGMP-PDE activity was high on estrus day. In PE rats, ovarian cGMP level was similar to that in adult rats on estrus and diestrus days but lower than that on proestrus and metestrus days; ovarian cGMP-PDE activity was lower than that on estrus days but similar as the other estrous cycle days. In addition, there was a significant negative correlation between ovarian cGMP level and cGMP-PDE activity during normal estrous cycles in the adult rat (r = -0.7715, N = 16, P < 0.05), but not in the postnatal rat (r = -0.1055, N = 20, P > 0.05). Together, the results of our present study indicated that ovarian cGMP levels were not dependent on cGMP PDE activity during early postnatal development, but highly dependent on cGMP-PDE activity in the adult rat. This implies that mechanisms of cGMP signaling involved in ovarian functions are stage-specific in the rat. PMID- 25117351 TI - Localization and expression of histone H2A variants during mouse oogenesis and preimplantation embryo development. AB - Epigenetic modifications of the genome, such as histone H2A variants, ensure appropriate gene activation or silencing during oogenesis and preimplantation embryo development. We examined global localization and expression of the histone H2A variants, including H2A.Bbd, H2A.Z and H2A.X, during mouse oogenesis and preimplantation embryo development. Immunocytochemistry with specific antibodies against various histone H2A variants showed their localization and changes during oogenesis and preimplantation development. H2A.Bbd and H2A.Z were almost absent from nuclei of growing oocytes (except 5-day oocyte), whereas H2A.X was deposited in nuclei throughout oogenesis and in preimplantation embryos. In germinal vesicle (GV) oocyte chromatin, H2A.Bbd was detected as a weak signal, whereas no fluorescent signal was detected in GV breakdown (GVBD) or metaphase II (MII) oocytes; H2A.Z showed intense signals in chromatin of GV, GVBD and MII oocytes. H2A. Bbd showed very weak signals in both pronucleus and 2-cell embryo nuclei, but intense signals were detected in nuclei from 4-cell embryo to blastula. The H2A.Z signal was absent from pronucleus to morula chromatin, whereas a fluorescent signal was detected in blastula nuclei. Our results suggest that histone H2A variants are probably involved in reprogramming of genomes during oocyte meiosis or after fertilization. PMID- 25117352 TI - Correlation of coronary artery stenosis evaluation with left heart structure and function by multi-slice computed tomography. AB - The aim of this study was to determine the impact of multi-slice computed tomography (MSCT) evaluation of coronary artery stenosis on left heart structure and systolic function. Coronary artery CT angiography was performed in 200 patients diagnosed with coronary heart disease, and then according to the AHA coronary artery 17-segment fractionation method, the Gensini score (GS) was determined for every narrow segment, and one-stop assessment of the correlation between left heart structure and function was performed. After the grouping of GS quartiles from low to high, there were differences between different patients with regard to LVDD, LADD, LVEDV, LVESV, MM, LVEF, and FS, while no difference in SV and CO. GS showed linear negative correlation with LVEF and FS, and linear positive correlation with LVDD, LADD, LVEDV, LVESV, and MM, while no correlation with SV and CO. That is, GS of coronary artery stenosis was negatively correlated with left ventricular systolic function and positively correlated with myocardial mass. The narrower the coronary artery, the worse the cardiac function and the higher the myocardial hypertrophy. Coronary artery stenosis was one of the important causes of the decrease in left ventricular systolic function and cardiac remodeling. PMID- 25117353 TI - Reason and treatment of failure of proximal femoral nail antirotation internal fixation for femoral intertrochanteric fractures of senile patients. AB - The cause of postoperative failure after the treatment of femoral intertrochanteric fracture with proximal femoral nail antirotation (PFNA) was analyzed, and the reoperative methods were examined. Nine failures of 308 femoral intertrochanteric fracture patients with PFNA were treated with femoral prosthesis total hip replacement (THR) and reoperative internal fixation. All nine patients were analyzed to determine the cause of failure. The causes of failed internal fixation in the intertrochanteric-fractured patients included perforation of the helical blade into the hip joint in three cases, cutting-out of the helical blade exit outside in two cases, and hip varus as a result of cutting-out the helical blade in two cases. Seven patients with failed internal fixation were treated with THR. Two patients who had femoral shaft fractures at the end of the nail were treated with longer PFNA. Faulty operative procedures, unsatisfactory reductions, serious osteoporosis, and incorrect positioning of the helical blade were the most important factors responsible for the failed internal fixation. Satisfactory results were achieved with THR and refixation relative to the causes of the failed internal fixation. PMID- 25117354 TI - Effect of Jianpi Bushen prescription on the expression of SHP-1 and apoptosis related genes in chemically damaged model mice. AB - We investigated the effect of Jianpi Bushen prescription (JBP) on the expression of the SHP-1 and apoptosis-related genes in chemically damaged model mice and a compound e-jiao slurry (EJS) group (positive control). Kunming mice received an abdominal injection of 100 mg/kg cyclophosphamide once a day for 3 consecutive days to induce chemical damage. The mice underwent lavage at a suspension of 0.1 g/kg low-dose JBP (100%), high-dose JBP (200%), and 0.2 mL/10 g EJS twice a day for 9 days. mRNA and protein expression of SHP-1 in bone marrow mononuclear cells was detected using real-time polymerase chain reaction and Western blot; mRNA expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax) protein was detected by in situ hybridization. Expression of SHP-1 and Bax mRNA was significantly upregulated in the model group compared to the control group (P < 0.05). Expression in the low-dose JBP, high-dose JBP, and EJS groups was significantly downregulated compared with the model group (P < 0.05). The low dose JBP group exhibited much lower SHP-1 and Bax mRNA expression levels. Compared with controls, Bcl-2 mRNA expression was significantly reduced in the model group (P < 0.05). Expression in the low-dose JBP, high-dose JBP, and EJS groups significantly increased compared with the model group (P < 0.05). The low dose JBP group showed much higher Bcl-2 mRNA expression. Therefore, JBP regulates the expression of the SHP- 1, Bax, and Bcl-2 genes in chemically damaged mice. PMID- 25117355 TI - Selection of sorghum hybrids grown under aluminum saturation. AB - The purpose of this study was to evaluate 165 hybrids derived from lines previously selected for aluminum (Al) tolerance. Nine check cultivars were used, eight commercial hybrids and one experimental hybrid. Hybrids were evaluated at three levels of Al saturation (0, 20 and 40% on average). The differences between the environments were significant. Environment with 0% Al saturation yielded 29.5% more than that with 40% Al saturation, showing the importance of genotype selection for acid soils. The best check cultivar was the hybrid DKB550. The hybrids AG1020 and AG1040 also performed well, where the latter was more tolerant but the former more responsive to environment improvement. The hybrid BRS304 was susceptible to high levels of Al saturation. The three commercial BRS hybrids (BRS310, BRS330 and BRS332) performed better than BRS304 at high Al saturation. The hybrid BRS330 was the best BRS hybrid to grow on a field with high Al saturation. The hybrid DKB559 performed well at high Al saturation but did not respond to environment improvement. The hybrids 727029, 727039, 729041, 729095, 729109, AG1040, and DKB550 were tolerant to higher levels of Al saturation and responsive to environment improvement, and showed good stability and adaptability at both low and high Al saturation. PMID- 25117356 TI - Genetic diversity and population structure in Harpadon nehereus based on sequence related amplified polymorphism markers. AB - In this study, the genetic diversity among ten populations of the Bombay duck was studied on the basis of sequence-related amplified polymorphism (SRAP). The ten populations were collected from the East China Sea and South China Sea areas. A total of 98 loci were obtained from 292 individuals using eight SRAP primers. The average proportion of polymorphic loci, genetic diversity (H), and Shannon's information index were 75.20%, 0.2478, and 0.3735, respectively. Nei's genetic distance and Shannon's information index between the ten populations ranged from 0.0410 to 0.3841 and from 0.2396 to 0.4506, and the averages Nei's gene diversity index (H = 0.2478) and Shannon's information index (I = 0.3735) at the population level were high. AMOVA showed that most of the variation was within populations (71.74%), and only 28.26% of the variation was between populations. The neighbor joining tree based on genetic distance revealed that significant genealogical structure existed throughout the examined range of the Bombay duck. The results demonstrated that SRAP marker was an effective tool for the assessment of genetic diversity in the Bombay duck. The results could be used for further protection of the germplasm resource of the Bombay duck. PMID- 25117358 TI - Polyploidy and epigenetic events in the evolution of Anura. AB - This article reviews the polyploidy events that have long been demonstrated to play a role in the evolution of Anura, while also discussing the importance of epigenetic control of gene expression and diversity. Findings on Brazilian autopolyploid anurans, mainly of the genus Odontophrynus, obtained in previous studies on their cytogenetics, chromatin ultrastructure, and molecular gene regulation are discussed here. Our data on genome duplication and on epigenetic events were analyzed here regarding phylogenetic trees, including the classic 2R model for vertebrate evolution and the growing evidence of similar epigenetic mechanisms in animal and allopolyploid plants. We propose that polyploidy and epigenetic events led to rapid Anura diversity and speciation. Also, recent advances in molecular studies in other organisms led us to revisit some controversial models of evolution. PMID- 25117357 TI - Molecular characterization and functional analysis of a Flowering locus T homolog gene from a Phalaenopsis orchid. AB - Warm day and cool night conditions significantly induce reproductive spike formation in Phalaenopsis plants; hence, determining the flowering mechanism regulating the reproductive transition is important. Flowering locus T (FT) plays important roles in flowering induction in several plants. To explore spike induction by warm days and cool nights in Phalaenopsis orchids, we isolated the FT (PhFT) from Phalaenopsis hybrid Fortune Saltzman. The cDNA of PhFT was 809-bp long and contained a 531-bp open reading frame encoding a putative protein of 176 amino acids, a 58-bp 5'-untranslated region (UTR), and a 220-bp 3'-UTR. The predicted molecular mass of PhFT was 19.80 kDa, with an isoelectric point of 8.68. The PhFT was predicted to possess the conserved functional regions of the phosphatidylethanolamine-binding protein superfamily. Nucleotide sequence data indicated that PhFT contained 3 introns and 4 exons. Sequence alignment and phylogenetic analyses of PhFT revealed high homology to the FT proteins of Cymbidium goeringii and Oncidium Gower Ramsey. Quantitative real-time polymerase chain reaction analysis indicated that PhFT mRNA was expressed in roots, apical leaves, mature leaves, and flowers. In flowers, PhFT was expressed more in developing floral buds than in mature flowers and was predominantly expressed in ovaries and petals. Ectopic expression of PhFT in Arabidopsis ft-1 mutants showed novel early-flowering phenotypes that lost their siliques. Our results indicated that the ectopic expression of PhFT could partially complement the late flowering defect in transgenic Arabidopsis ft-1 mutants. Our findings suggest that PhFT is a putative FT homolog in Phalaenopsis plants that regulates flowering transition. PMID- 25117359 TI - Molecular study of Astyanax altiparanae (Osteichthyes, Characidae) as a probable species complex. AB - Astyanax altiparanae, belonging to the bimaculatus group, which includes species with similar colors and morphology, occurs in the upper Parana River basin. As the use of mitochondrial DNA has made great strides in the diagnosis of species, in previous researches, two strains were detected in A. altiparanae with a high divergence in the D-loop region, provisionally called AltoPR and AltoPR-D. Evidence led to the hypothesis that the two strains did not belong to the same species. Phylogenetic hypotheses were produced by maximum-likelihood. Mean internal distances of the AltoPR and AltoPR-D groups were respectively 0.002 and 0.003, with the distance between them being 0.037. Sequences from GenBank of specimens collected from the Paraiba do Sul River basin were also divided into two groups, of which one may be identified as AltoPR. Since the other group provided an intermediate distance when compared to AltoPR-D, an in-depth investigation was required. The other species analyzed showed a greater distance and was revealed to be a monophyletic taxon. The results suggested that they are really two species and that neither corresponds to the other species used in the current study. PMID- 25117360 TI - Value of C-arm computed tomography in radiofrequency ablation of small lung lesions. AB - This study aimed to explore the value of C-arm computed tomography (CT) applications in radiofrequency ablation (RFA) of small lung lesions. The puncture success rate, cumulative survival rate, tumor response rate, complications, and radiation dose during C-arm CT-guided RFA of 36 small lung lesions in 34 patients were analyzed. In 35 RFA procedures for 36 small lung lesions, the puncture success rate was 100%. There were 7 cases of complications, including 4 cases of pneumothorax (puncture suction or closed chest drainage was not required) and 3 cases of hemoptysis. The cumulative survival rate in the 34 patients after RFA was 100% at 6 months, 69.0% at 1 year, and 60.0% at 2 years. In assessments of 36 foci imaged during the follow-up period, the total response rates at 1 month, 3 months, and 6 months were 77.8% (28/36), 69.7% (23/33), and 61.3% (19/31), respectively. The mean cumulative dose and average effective dose during surgery were 120.1 +/- 61.4 mGy and 3.5 +/- 1.7 mSv, respectively. The application of C arm CT to RFA of small lung lesions could provide abundant information to the surgeon and increase the lesion puncture success rate and is considered to be a promising image-guided technology. PMID- 25117361 TI - Identification of floral genes for sex determination in Calamus palustris Griff. by using suppression subtractive hybridization. AB - Calamus palustris Griff. is an economically important dioecious rattan species in Southeast Asia. However, dioecy and onset of flowering at 3-4 years old render uncertainties in desired female:male seedling ratios to establish a productive seed orchard for this rattan species. We constructed a subtractive library for male floral tissue to understand the genetic mechanism for gender determination in C. palustris. The subtractive library produced 1536 clones with 1419 clones of high quality. Reverse Northern screening showed 313 clones with differential expression, and sequence analyses clustered them into 205 unigenes, including 32 contigs and 173 singletons. The subtractive library was further validated with reverse transcription-quantitative polymerase chain reaction analysis. Homology identification classified the unigenes into 12 putative functional proteins with 83% unigenes showing significant match to proteins in databases. Functional annotations of these unigenes revealed genes involved in male flower development, including MADS-box genes, pollen-related genes, phytohormones for flower development, and male flower organ development. Our results showed that the male floral genes may play a vital role in sex determination in C. palustris. The identified genes can be exploited to understand the molecular basis of sex determination in C. palustris. PMID- 25117362 TI - Characteristics of growth traits and their effects on body weight of G1 individuals in the mud crab (Scylla paramamosain). AB - The mud crab (Scylla paramamosain) is considered a potentially important marine crab species for selective breeding. Here, we first examined sex ratio and differences in 16 growth traits between females and males in a G1 population of S. paramamosain, and we then analyzed the correlation between these growth traits and their effects on body weight (BW). Of these growth traits, nine were significantly different between sexes. In females, the correlation coefficients in all trait pairs ranged from 0.524 to 0.997. The traits carapace length (CL) and distance between lateral spine 2 (DLS2) significantly affected BW directly, with the path coefficients being 1.124 and -0.186, respectively. The determination coefficients of traits CL and DLS2 to BW were 1.263 and 0.035 with the total value being 0.951, indicating that the two traits were the key factors affecting BW. In males, the correlation coefficients in all trait pairs ranged from 0.881 to 0.999. The three traits body height (BH), fixed finger height of the claw (FFHC), and meropodite length of pereopod 2 (MLP2) significantly affected BW directly, with the path coefficients being 0.484, 0.300, and 0.225, respectively. The determination coefficients of traits BH, FFHC and MLP2 to BW were 0.234, 0.090 and 0.051, with the total value being 0.967, indicating that these three traits played a key role in affecting BW. Moreover, we constructed two best-fit linear regression equations, which were Y (BW) = 4.969 X1 (CL) - 0.758 X2 (DLS2) - 140.177 and Y (BW) = 3.806 X1 (BH) + 2.371 X2 (FFHC) + 1.725 X3 (MLP2) - 123.559 in females and males, respectively. PMID- 25117363 TI - Effects of simulated weightlessness on cellular morphology and biological characteristics of cell lines SGC-7901 and HFE-145. AB - We investigated the effects of simulated weightlessness on cellular morphology, proliferation, cell cycle, and apoptosis of the human gastric carcinoma cell line SGC-7901 and the human gastric normal cell line HFE-145. A rotating clinostat was used to simulate weightlessness. The Image-Pro4.5 image analysis system was used for morphometric analysis. Proliferating cell nuclear antigen expression was examined by immunohistochemical staining. Changes in the cell cycle were examined using a cytometer. Apoptosis was measured using the terminal dUTP nick-end labeling (TUNEL) method. When subjected to simulated weightlessness, the cellular morphology of SGC-7901 cells was changed at 12, 24, 48, and 72 h, cell conversion from the G1 to S phase was blocked, proliferation was inhibited at 48 and 72 h, and the apoptosis index was increased at 72 h. The same changes were observed for HFE-145 cells at 12 h when subjected to simulated weightlessness, but no significant changes were found afterward compared with controls. SGC-7901 cells change their cellular morphology and biological characteristics during clinostat simulated weightlessness at 72 h, but HFE-145 cells only change at 12 h and adapt to simulated weightlessness after that point. PMID- 25117364 TI - Comparative study of DNA extraction methodologies from goat sperm and its effects on polymerase chain reaction analysis. AB - Successful DNA extraction is indispensable for molecular methods based on polymerase chain reaction (PCR); however, goat sperm DNA extraction is limited. Thus, the aim of this study was to evaluate three methods to extract DNA from goat sperm for use in PCR. Eight goat semen pools were used for DNA extraction by using the DNeasy Blood & Tissue Kit, phenol-chloroform, and Chelex-100 methods. DNA samples were analyzed spectrophotometrically to determine the DNA concentration and purity, visualized on 0.8% agarose gel, and used at different amounts (150, 100, 50, 10, and 1 ng) for PCR with electrophoresis, followed by 1.5% agarose gel electrophoresis. The quantity of DNA extracted with Chelex-100 was higher (P < 0.05) than that obtained with either the DNeasy Blood & Tissue Kit or the phenol-chloroform method, with the phenol-chloroform method yielding a greater quantity (P < 0.05) than the kit. The DNeasy Blood & Tissue Kit produced a higher (P < 0.05) purity product than the Chelex-100 method, and all samples obtained by the three protocols were positive for DNA, as assessed by electrophoresis. All of the different concentrations of DNA produced by these methods were amplified by PCR, although for DNA produced by the phenol-chloroform method, PCR was only possible after complementary purification. In conclusion, the Chelex-100 method is cheap, secure, simple, fast, and effective, and is a potential tool for extracting goat sperm DNA without limitations in PCR. PMID- 25117365 TI - Screening and characterization of new microsatellite markers in Fenneropenaeus penicillatus. AB - Fenneropenaeus penicillatus, with high protein and low fat, is a commercially important aquatic product in China. Microsatellite loci were developed according to the protocol of fast isolation by amplified fragment length polymorphism of sequences containing repeats. Eight new polymorphic microsatellite markers for F. penicillatus were identified, and 32 wild individuals were used to evaluate the degree of polymorphism of these markers. The polymorphism information content ranged from 0.2703 to 0.7598, and the number of alleles per locus varied from 3 to 6. The observed and expected heterozygosities were 0.1613-0.5556 and 0.2347 0.7387, respectively. No significant deviations from Hardy-Weinberg equilibrium (P > 0.00625) were detected. These polymorphic microsatellite loci will be useful to study the genetic diversity and population structure of F. penicillatus. PMID- 25117366 TI - Influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. AB - We examined the influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury. Sixty rats with spinal cord injury were divided into an experimental group and a control group and given neural stem cells or an equivalent amount of phosphate-buffered saline by intravenous transplantation, respectively. Basso, Beattie, and Bresnahan (BBB) motor function assessment was performed in rats at different times after transplantation, and von Willebrand factor (vWF) immunofluorescence and Western blot analysis of vascular endothelial growth factor (VEGF) protein were also performed. The BBB scores of rats in the 2 groups were both zero before transplantation. The BBB score gradually increased over time. The BBB score of the experimental group showed no significant difference compared with that of the control group (P > 0.05) 7 days after transplantation. The BBB score of the experimental group was significantly improved compared with that of the control group 14 days after transplantation (P < 0.05). vWF-positive cells and VEGF protein expression in the experimental group were significantly increased compared with those in the control group 7 and 14 days after transplantation, respectively (P < 0.05). Neural stem cell transplantation may promote angiogenesis by inducing VEGF expression as well as improve functional recovery of limb movements. PMID- 25117367 TI - Source of bacterial RNA in chronic otitis media with effusion. AB - The purpose of this study was to investigate whether the bacterial RNA detected by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR methods in middle ear effusion (MEE) for pediatric chronic otitis media with effusion (OME) originated from live bacteria. Degradation of RNA was observed by spectroscopic analysis; we also investigated the effect of MEE on the digestive activity of RNase. The optical density of RNA solution was stable within 3 h. MEE could not degrade the RNA, while RNase could rapidly digest the RNA. MEE significantly inhibited the digestive activity of RNase, and the inhibitory effect was correlated with MEE concentration. The bacterial DNA and RNA detected by PCR and RT-PCR methods may not originate from live bacteria, but might instead originate from residues from previous bacterial infection(s). Chronic OME is not an infection of live bacteria, and therefore, antibiotics should be used with caution for clinical treatment of pediatric chronic OME. PMID- 25117368 TI - Development of novel simple sequence repeat markers from a genomic sequence survey database and their application for diversity assessment in Jatropha curcas germplasm from Guatemala. AB - The last few years have seen a significant increase in the number of large-scale sequencing projects generating whole genome databases. These sequence databases can be surveyed (genome sequence survey) for tandem repeats as an alternative means to develop microsatellites for monitoring and selecting natural populations and cultivars of Jatropha curcas. A total of 100 tandem repeats were revealed from mining 368 genomic surveyed sequences available in the Kazusa DNA Research Institute database. Twenty microsatellite sequences were successfully amplified, resulting in repeatable and scorable polymerase chain reaction products. Genotyping of J. curcas accessions from the Guatemalan population revealed 18 polymorphic loci. The average number of alleles per locus was 6.9, and allelic sizes ranged from 94 to 299 bp. Expected and observed heterozygosities ranged from 0.118 to 0.906 and from 0.082 to 0.794, respectively. Polymorphic information content values ranged from 0.114 (JcSSR-34) to 0.886 (JcSSR-33) with an average of 0.627. Analysis with Micro-Checker indicated few null alleles for locus JcSSR-37 in Guatemalan populations, which may be a possible cause of its deviation from Hardy-Weinberg equilibrium, even after Bonferroni's correction. No loci showed significant linkage disequilibrium. These microsatellite loci are expected to be valuable molecular markers in J. curcas because they show high levels of polymorphism and heterozygosity. PMID- 25117369 TI - Formation of and countermeasures for subacute coronary stent thrombosis in elderly diabetic patients. AB - The aim of this study was to evaluate and investigate the pathogenetic mechanism and countermeasures of subacute thrombosis (SAT) after coronary stenting in elderly diabetic patients. The clinical characteristics and pathogenetic mechanisms in 3 cases of SAT after stent implantations in elderly diabetic patients were retrospectively examined to determine the treatment strategies for SAT. Among 98 patients with diabetes who had coronary stents implanted or were >60 years of age, three (3.06%) had SAT. One case of SAT was diagnosed by angiography; coronary balloon dilatation, thrombolysis, and re-perfusion resulted in full recovery in this case. The second case involved potential SAT, and in the third case, SAT was not ruled out. Two cases were characteristic of ST-segment elevation myocardial infarction, and one case, in which SAT was not ruled out, resulted in sudden death. SAT within a stent may be related to intraoperative stent malapposition caused by a grade C lesion, age, diabetes, chronic total occlusion, or postoperative irregular administration of medication. PMID- 25117372 TI - Repeated whole-lung lavage for unremitting pulmonary alveolar proteinosis: a eight-year follow-up of a case. AB - Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome that was first described in 1958. To date, whole-lung lavage (WLL) is still the gold-standard therapy for PAP. Herein, we report the case of a male patient who was diagnosed with PAP by open-lung biopsy 8 years prior to presentation at our clinic. The man underwent his first WLL in 2004 and showed marked clinical and radiological improvement after the operation. However, after his original presentation, proteinaceous material continued to accumulate in his lungs. Lavage was performed four additional times, but these attempts failed to arrest the decline in pulmonary function. Each lavage resulted in significant, although transient, clinical improvement. PMID- 25117371 TI - Variants -250G/A and -514C/T in the LIPC gene are associated with hypertensive disorders of pregnancy in Chinese women. AB - We examined the influence of the promoter polymorphisms -250G/A (rs2070895) and 514C/T (rs1800588) in the human hepatic lipase (LIPC) gene on dyslipidemia and hypertensive disorders complicating pregnancy (HDCP) in a Chinese population. Clinically defined HDCP patients (N = 321) and healthy pregnant women (N = 331) were recruited and genotyped using polymerase chain reaction-restriction fragment length polymorphism for the two LIPC single nucleotide polymorphisms (SNPs). The results showed significant relationships between HDCP and triglycerides, apolipoprotein A1, and high-density lipoprotein cholesterol (P < 0.05), which confirmed that HDCP was accompanied by dyslipidemia. The results also demonstrated that in gestational hypertension (GH) patients, both total cholesterol (TC) and systolic blood pressure (SBP) levels were related to the two SNPs (P <= 0.004), although no significant association was found between HDCP and LIPC genotypes or alleles. Significant linkage disequilibrium of the two SNPs was found in both HDCP patients (R(2) = 0.867) and controls (R(2) = 0.91). Body mass index (BMI) was associated with -250G/A in women with mild preeclampsia (MPE) (P = 0.01). Carriers of the mutant homozygote -250AA genotype presented higher BMI in the MPE group. In conclusion, the LIPC -250G/A and -514C/T variants influenced TC and SBP levels in GH patients and the BMI level in the MPE group, although there was no evidence to validate an association between HDCP and LIPC allele, genotype, or haplotype frequencies. PMID- 25117370 TI - Evaluation of attenuated Salmonella choleraesuis-mediated inhibin recombinant DNA vaccine in rats. AB - DNA vaccination has been studied intensively as a potential vaccine technology. We evaluated the effect of an attenuated Salmonella choleraesuis-mediated inhibin DNA vaccine in rats. First, 15 rats were treated with different doses of an inhibin vaccine to evaluate vaccine safety. Next, 30 rats were divided into 3 groups and injected intramuscularly with the inhibin vaccine two (T1) or three times (T2) or with control bacteria (Con) at 4-week intervals. The inhibin antibody levels increased [positive/negative well (P/N) value: T1 vs Con = 2.39 +/- 0.01 vs 1.08 +/- 0.1; T2 vs Con = 2.36 +/- 0.1 vs 1.08 +/- 0.1, P < 0.05] at week 2 and were maintained at a high level in T1 and T2 until week 8, although a small decrease in T2 was observed at week 10. Rats in the T1 group showed more corpora lutea compared with the Con group (10.50 +/- 0.87 vs 7.4 +/- 0.51, P < 0.05). Estradiol (0.439 +/- 0.052 vs 0.719 +/- 0.063 ng/mL, P < 0.05) and progesterone (1.315 +/- 0.2 vs 0.737 +/- 0.11 ng/mL, P < 0.05) levels differed significantly at metestrus after week 10 between rats in the T1 and Con groups. However, there were no significant differences in body, ovary, uterus weights, or pathological signs in the ovaries after immunization, indicating that this vaccine is safe. In conclusion, the attenuated S. choleraesuis-mediated inhibin vaccine may be an alternative to naked inhibin plasmids for stimulating ovarian follicular development to increase the ovulation rate in rats. PMID- 25117373 TI - A case-control study indicates that the TRIB1 gene is associated with pancreatic cancer. AB - Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues that form the pancreas. To investigate whether the tribbles homolog 1 (Drosophila) gene (TRIB1) is associated with pancreatic cancer in the Chinese Han population, we conducted this case-control study and genotyped 3 single nucleotide polymorphisms (rs2980879, rs2980874, and rs2235108) of the TRIB1 gene in 182 patients and 359 normal controls of Chinese Han origin and analyzed their association. The results showed that the rs2980879 polymorphism was associated with pancreatic cancer [allele: P = 0.023434, genotype: P = 0.03005; odds ratio (OR) and 95% confidence interval (CI) = 0.727788 (0.552664 0.958404)], whereas the rs2980874 polymorphism had no association with pancreatic cancer [allele: P = 0.749885, genotype: P = 0.699533; OR and 95%CI = 1.041981 (0.809196-1.341734)], and the rs2235108 polymorphism was not associated with the disease [allele: P = 0.629475, genotype: P = 0.547534, OR and 95%CI = 1.128290 (0.690829-1.842770)]. Haplotype analyses and linkage disequilibrium tests were also conducted, and the results showed that these 3 loci are not in the same block. In conclusion, our study indicated that the TRIB1 gene is associated with pancreatic cancer. More studies with larger samples are needed in order to support this finding. PMID- 25117374 TI - Selection of DNA barcoding loci and phylogenetic study of a medicinal and endemic plant, Plectranthus asirensis J.R.I. Wood from Saudi Arabia. AB - Genuine medicinal plant materials are very important for potential crude drug production, which can be used to cure many human diseases. DNA barcoding of medicinal plants is an effective way to identify adulterated or contaminated market materials, but it can be quite challenging to generate barcodes and analyze the data to determine discrimination power. The molecular phylogeny of a plant species infers its relationship to other species. We screened the various loci of the nuclear and chloroplast genome for the barcoding of Plectranthus asirensis, an endemic plant of Saudi Arabia. The chloroplast genome loci such as rps16 and rpoB showed maximum similarity to taxa of the same and other genera via BLAST of the National Center for Biotechnology Information (NCBI) GenBank database; hence, they are less preferable for the development of a DNA barcode. However, nrDNA-ITS and chloroplast loci rbcL and rpoC1 showed less similarity via BLAST of the NCBI GenBank database; therefore, they could be used for DNA barcoding for this species. PMID- 25117375 TI - Beneficial metabolic phenotypes caused by loss-of-function APOC3 mutations. PMID- 25117376 TI - Stiffness of cross-linked poly(dimethylsiloxane) affects bacterial adhesion and antibiotic susceptibility of attached cells. AB - In this study, Escherichia coli RP437 and Pseudomonas aeruginosa PAO1 were used as model strains to investigate the early stage biofilm formation on poly(dimethylsiloxane) (PDMS) surfaces with varying stiffness, which were prepared by controlling the degree of cross-linking (base:curing agent ratios of 5:1, 10:1, 20:1, and 40:1 were tested). An inverse correlation between cell adhesion and substrate stiffness was observed for both species. Interestingly, it was found that the cells attached on relatively stiff substrates (5:1 PDMS) were significantly smaller than those on relatively soft substrates (40:1 PDMS). In addition to the difference in size, the cells on 5:1 PDMS substrates were also found to be less susceptible to antibiotics, such as ofloxacin, ampicillin, and tobramycin, than the cells attached on 40:1 PDMS substrates. These results reveal that surface stiffness is an important material property that influences the attachment, growth, and stress tolerance of biofilm cells. PMID- 25117377 TI - Microfluidic genotyping by rapid serial PCR and high-speed melting analysis. AB - BACKGROUND: Clinical molecular testing typically batches samples to minimize costs or uses multiplex lab-on-a-chip disposables to analyze a few targets. In genetics, multiple variants need to be analyzed, and different work flows that rapidly analyze multiple loci in a few targets are attractive. METHODS: We used a microfluidic platform tailored to rapid serial PCR and high-speed melting (HSM) to genotype 4 single nucleotide variants. A contiguous stream of master mix with sample DNA was pulsed with each primer pair for serial PCR and melting. Two study sites each analyzed 100 samples for F2 (c.*97G>A), F5 (c.1601G>A), and MTHFR (c.665C>T and c.1286A>C) after blinding for genotype and genotype proportions. Internal temperature controls improved melting curve precision. The platform's liquid-handling system automated PCR and HSM. RESULTS: PCR and HSM were completed in a total of 12.5 min. Melting was performed at 0.5 degrees C/s. As expected, homozygous variants were separated by melting temperature, and heterozygotes were identified by curve shape. All samples were correctly genotyped by the instrument. Follow-up testing was required on 1.38% of the assays for a definitive genotype. CONCLUSIONS: We demonstrate genotyping accuracy on a novel microfluidic platform with rapid serial PCR and HSM. The platform targets short turnaround times for multiple genetic variants in up to 8 samples. It is also designed to allow automatic and immediate reflexive or repeat testing depending on results from the streaming DNA. Rapid serial PCR provides a flexible genetic work flow and is nicely matched to HSM analysis. PMID- 25117378 TI - Effects of a very congested match schedule on body-load impacts, accelerations, and running measures in youth soccer players. AB - PURPOSE: To analyze the effects of a very congested match schedule on the total distance (TD) covered, high-intensity-running (HIR) distance, and frequency of accelerations and body-load impacts (BLIs) performed in a team of under-15 soccer players (N=10; 15.1+/-0.2 y, 171.8+/-4.7 cm, 61+/-6.0 kg) during an international youth competition. METHODS: Using global positioning systems, player performances were repeatedly monitored in 5 matches performed over 3 successive days. RESULTS: Significant differences were observed between matches (P<.05) for the frequency of accelerations per minute, BLIs, and BLIs per minute. No differences were observed for the TD covered, TD run per minute, number of high-intensity runs, distance covered in HIR, per-minute peak running speed attained, or frequency of accelerations. The frequency of accelerations per minute decreased across the competition while BLIs were higher during the final than in all other matches. CONCLUSIONS: These results suggest that BLIs and acceleration might be used as an alternative means to represent the external load during congested match schedules rather than measures related to running speed or distance covered. PMID- 25117380 TI - QT Interval Prolongation Associated with Azithromycin/Methadone Combination. AB - This report documents the occurrence of QT prolongation in a 57-year old man, on methadone replacement therapy, treated with azithromycin for community acquired pneumonia. This case highlights a hitherto unknown drug interaction. In light of ever-increasing use of azithromycin, it is imperative that azithromycin be used with caution in patients who are already on drugs that are known to cause QT prolongation or that cause torsades de pointes. PMID- 25117379 TI - Electrospun polyurethane/hydroxyapatite bioactive scaffolds for bone tissue engineering: the role of solvent and hydroxyapatite particles. AB - Polyurethane (PU) is a promising polymer to support bone-matrix producing cells due to its durability and mechanical resistance. In this study two types of medical grade poly-ether urethanes Z3A1 and Z9A1 and PU-Hydroxyapatite (PU-HA) composites were investigated for their ability to act as a scaffold for tissue engineered bone. PU dissolved in varying concentrations of dimethylformamide (DMF) and tetrahydrofuran (THF) solvents were electrospun to attain scaffolds with randomly orientated non-woven fibres. Bioactive polymeric composite scaffolds were created using 15 wt% Z3A1 in a 70/30 DMF/THF PU solution and incorporating micro- or nano-sized HA particles in a ratio of 3:1 respectively, whilst a 25 wt% Z9A1 PU solution was doped in ratio of 5:1. Chemical properties of the resulting composites were evaluated by FTIR and physical properties by SEM. Tensile mechanical testing was carried out on all electrospun scaffolds. MLO A5 osteoblastic mouse cells and human embryonic mesenchymal progenitor cells, hES MPs were seeded on the scaffolds to test their biocompatibility and ability to support mineralised matrix production over a 28 day culture period. Cell viability was assayed by MTT and calcium and collagen deposition by Sirius red and alizarin red respectively. SEM images of both electrospun PU scaffolds and PU HA composite scaffolds showed differences in fibre morphology with changes in solvent combinations and size of HA particles. Inclusion of THF eliminated the presence of beads in fibres that were present in scaffolds fabricated with 100% DMF solvent, and resulted in fibres with a more uniform morphology and thicker diameters. Mechanical testing demonstrated that the Young's Modulus and yield strength was lower at higher THF concentrations. Inclusion of both sizes of HA particles in PU-HA solutions reinforced the scaffolds leading to higher mechanical properties, whilst FTIR characterisation confirmed the presence of HA in all composite scaffolds. Although all scaffolds supported proliferation of both cell types and deposition of calcified matrix, PU-HA composite fibres containing nano-HA enabled the highest cell viability and collagen deposition. These scaffolds have the potential to support bone matrix formation for bone tissue engineering. PMID- 25117381 TI - The economic and medical costs of alcohol consumption in Japan. PMID- 25117382 TI - Chemokine Receptor 7 Implications of Spleen Dendritic Cells in Multiple-organ Dysfunction Syndrome in Mice. AB - OBJECTIVE: This study aims to explore the chemokine receptor 7 (CCR7) expression of spleen dendritic cells (DCs) and their role in the changes of migration and activity of spleen DCs in multiple-organ dysfunction syndrome (MODS). METHODS: The MODS model of mice was reproduced. The mice were randomly assigned to the following groups: normal, three-hour to six-hour, 24-hour to 48-hour, and 10-day to 12-day post-zymosan injection. CD11c and CD205 were analysed by immunohistochemistry; the expressions of CD86 and CCR7 of DCs were studied using flow cytometry analyses. RESULTS: In normal mice, many DCs were found at the margin between the red and white pulp. In the three-hour to six-hour and 24-hour to 48-hour group, DC effectively upregulated CD86 and CCR7, and they were distributed in T- cell areas. In the 10-day to 12-day group, DCs were distributed at the margin by the immature form. CONCLUSION: The CCR7 expression level of DCs had close correlations with the migration of DCs. Chemokine receptor 7 can be used to evaluate the migration and functional activity of DCs in MODS. PMID- 25117383 TI - The Changes of Muscle FGF-6 Expression at Different Time Points after Exercise induced Muscle Damage. AB - OBJECTIVE: To investigate the changes of fibroblast growth factor (FGF)-6 expression in the regeneration and repair process after exercise-induced muscle damage (EIMD) and the relationship with skeletal muscle regeneration and repair. METHODS: The expression of FGF-6 at different time points was examined by reverse transcription-polymerase chain reaction (PCR) and immunohistochemistry staining after a downhill treadmill exercise. Skeletal muscle injury and regeneration at different times after EIMD was assessed by haematoxylin and eosin (H and E) staining. RESULTS: The FGF-6 protein expression was initially elevated and followed by a gradual reduction, while the changes of FGF-6 mRNA were almost all raised after the treadmill exercise. CONCLUSION: The results point out that FGF-6 is closely related to skeletal muscle regeneration and repair, probably implying a dual function in muscle regeneration. PMID- 25117384 TI - Study on vascular endothelial growth factor and its receptor in the vitreous of diabetic rats. AB - OBJECTIVE: To investigate the vitreous level of vascular endothelial growth factor (VEGF) and kinase insert domain-containing receptor (KDR) in diabetic rats, and to explore the role of VEGF and KDR in diabetic retinopathy. METHODS: Eighty-four adult Wistar rats were randomly divided into two groups. Fifty-eight rats in group A were injected intraperitoneally with streptozotocin to induce diabetes and 20 rats in group B were injected with physiological saline. Blood glucose meter was used to detect the blood glucose level at 72 hours after injection; blood glucose level >= 16.67 mmol/L was considered to be successful modelling. Blood glucose level was assayed and body mass was measured on the same modelling day, one week, two weeks and four weeks after modelling. Four weeks after modelling, the vitreous was taken, and the VEGF and KDR levels were detected by enzyme-linked immunosorbent assay (ELISA). The eyeballs were fixed with paraform and embedded by petrolin for haematoxylin and eosin (H and E) staining. RESULTS: Forty-two rats survived and 16 rats died in group A. No rats died in group B. The blood glucose at one week, two weeks and four weeks between the two groups had statistical differences (p < 0.05). The weight at one week and two weeks between the two groups was not different but there was statistical difference at four weeks between the two groups (p < 0.01). The ELISA results showed that the VEGF and KDR levels were 0.276 +/- 0.026 ng/mL and 2.936 +/- 0.295 ng/mL in group A, 0.231 +/- 0.021 ng/mL and 2.394 +/- 0.227 ng/mL in group B, respectively. The VEGF and KDR levels of group A were higher than those of group B (p < 0.05). CONCLUSIONS: The changes of VEGF and KDR levels in the vitreous of diabetic rats were related to the early retinopathy induced by diabetes. PMID- 25117385 TI - Role of interleukin-6, gamma interferon and adenosine deaminase markers in management of pleural effusion patients. AB - OBJECTIVE: Pleural effusion is a common diagnostic and clinical problem. Neoplasms and tuberculosis are the most frequent diagnostic causes of such effusions. Conventional laboratory methods for diagnosis of such effusion are inefficient because tubercle bacilli are rarely seen in direct examinations of pleural fluid. The present study evaluates interleukin-6 (IL-6), gamma interferon (IFN-gamma) and adenosine deaminase (ADA) as diagnostic tools in pleural effusion. MEHTODS: Interleukin-6, IFN-gamma and ADA were measured in pleural fluid from the patients, with exudative pleural effusion from tuberculous, malignant and postpneumonic origin and transudative pleural effusion of systemic origin in order to evaluate the diagnostic utility of these. RESULTS: The three markers were detectable in all effusions with significantly high levels in exudative as compared to transudative effusions. There was a statically significant difference noticed in tuberculous as compared to malignant and postpneumonic origin and transudative pleural effusion. CONCLUSION: We concluded that IL-6, IFN-gamma and ADA levels in pleural effusion are sensitive parameters to differentiate an exudate from a transudate and they can also differentiate exudates of different aetiology. Finally, the results suggest that there is a remarkable difference in production of these three markers in exudative pleural effusions as compared to transudative pleural effusions. PMID- 25117386 TI - Diagnostic accuracy of spot and timed measurements of urinary albumin concentration to determine microalbuminuria in sickle cell disease. AB - OBJECTIVE: Whereas measurement of albumin:creatinine ratio (ACR) in spot urine samples is indicated for determining microalbuminuria, its performance or that of urinary albumin excretion rate (UAER) in predicting microalbuminuria in sickle cell disease (SCD) is unclear. We therefore tested the diagnostic performance of these measures in spot and timed urine samples in predicting a UAER in 24-hour samples. METHODS: Thirty participants with SCD had spot, two-hour and four-hour, followed by 24-hour urine collections for ACR, urinary albumin concentration (UAC) and UAER determinations. Receiver operating characteristic (ROC) curve analyses were performed. RESULTS: The areas under the ROC curves for microalbuminuria were 0.99 (CI: 0.97, 1.00) for ACR and 0.97 (CI: 0.92, 1.00) for UAC in spot urine samples. For ACR, at the cut-point of 4.13 mg/mmol, there was 100% sensitivity and 82.6% specificity, allowing an 86.2% correct classification. At the cut-point of UAC = 20.9 mg/L, there was 100% sensitivity and 73.9% specificity, allowing a 79.3% correct classification. Corresponding areas for microalbuminuria in two-hour timed samples were 0.99 (CI: 0.95, 1.00) for ACR and 0.96 (CI: 0.89, 1.00) for UAER.For ACR, the cut-point was 4.64 mg/mmol with 83.3% sensitivity and 91.3% specificity, allowing an 89.7% correct classification. Similarly for UAER, at the cut-point of 21.8 ug/min, there was 83.3% sensitivity and 91.3% specificity, allowing 89.7% correct classification. CONCLUSIONS: The diagnostic performance of ACR and UAC in a spot as well as ACR and UAER in two hour timed urine samples in patients with SCD is excellent. Healthcare professionals can confidently utilize these measures in this patient population. PMID- 25117387 TI - Observer Variability in Sonographic Measurement of Kidney Sizes among Children in Benin-City, Nigeria. AB - AIM: To assess the level of inconsistency in replicating sonographic kidney size measurements in a population of healthy Nigerian children. SUBJECTS AND METHODS: In this prospective cross-sectional study, convenience sampling technique was used to select a sample of Nigerian children. Both consent from participants and ethical approval from the local authority were obtained before the study commenced. Three radiologists carried out the replicate sonographic measurements using a DP-1100 mechanical sector scanner with a 3.5 MHz convex probe. All examinations were done with subjects in the supine oblique position. Longitudinal and transverse scans were performed. Renal lengths and widths were measured from the longitudinal scans while thickness was measured from the transverse scans. Renal volumes were calculated with the ellipsoid formula. Analysis of variance, Student's t-test, Pearson's correlation coefficient and z-test were used to test the statistical significance of results. SPSS version 17.0 was used in the analysis of results while statistical significance of all results was tested at p < 0.05. RESULTS: Mean intra-observer measurement errors in replicate sonographic measurements of kidney sizes ranged from 0.36-0.43 cm, 0.22-0.63 cm, 0.37-0.52 cm and 5.93-9.62 ml for kidney length, width, thickness and volume, respectively. Mean inter-observer measurement errors were in the range of 0.29-0.48 cm, 0.18 0.23 cm, 0.34-1.82 cm and 5.92-7.28 ml for length, width, thickness and volume, respectively. Mean intra-observer errors were not statistically significant (p < 0.05) but mean inter-observer errors were (p < 0.05). Differences in all measurement errors of right and left kidney length, width, thickness and volume were not statistically significant (p > 0.05). Measurement errors correlated weakly with kidney sizes. Observer errors in renal length were not significantly different from what was reported among Caucasians (p > 0.05) whereas that of volume was (p < 0.05). CONCLUSION: Errors in replicate sonographic kidney size measurements obtained by a single observer were less than errors in the same measurements by different observers; therefore, replicate sonographic measurements by a single observer were more consistent in this population. PMID- 25117388 TI - The Prevalence of Sexual Dysfunction among the Patients with End Stage Renal Disease in Jamaica. AB - BACKGROUND: Sexual performance and gratification impact quality of life. Although recognized in the literature as a problem, sexual dysfunction among patients with end stage renal disease (ESRD) has never been studied in Jamaica. SUBJECTS AND METHOD: The prevalence of sexual dysfunction was determined among 268 adult Jamaican patients (166 males, 102 females) with ESRD who had been on haemodialysis for at least three months. Erectile dysfunction (ED) was assessed using the International Index of Erectile Function (IIEF). Female sexual dysfunction (FSD) was determined using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and International Classification of Diseases (ICD)-10 classifications of sexual disorders. Prevalence, severity of sexual dysfunctions and relationships with the primary aetiology of ESRD and anaemia were assessed. RESULTS: Erectile dysfunction, desire and orgasmic disorderS were found in 91.4%, 88.3%, and 81.6% of male subjects, respectively. The majority of male patients were dissatisfied with their performance at intercourse after progressing to ESRD. Hypoactive sexual disorder, sexual arousal and orgasmic disorders, and aversion sexual disorder were prevalent, found in 96%, 88.1% and 87.1% of female patients. All diabetic patients with ESRD reported hypoactive sexual disorder and orgasmic dysfunction; arousal disorder was found in 94.7%. Aversion sexual disorder was found more among patients with underlying chronic glomerulonephritis. All patients with severe anaemia were found to have hypoactive sexual disorder and among these, 87.5% and 97.8% had severe arousal and orgasmic disorders, respectively. CONCLUSION: Sexual dysfunction among patients with ESRD in Jamaica was prevalent in males and females. Associations exist between sexual dysfunction and diabetes mellitus, chronic glomerulonephritis and anaemia. PMID- 25117389 TI - Comparison of ultrasonographic estimated fetal weight and actual birthweight performed by residents in training at the university hospital of the west indies. AB - OBJECTIVE: To determine the correlation of ultrasonographic estimation of fetal weight and actual birthweight and the impact of the level of resident's training on the results. METHODS: A prospective study of 90 women with term pregnancies. Ultrasound estimated fetal weight (EFW) was calculated by a preprogrammed Hadlock formula. Days from ultrasound to delivery were less than seven. The EFW was compared to the actual birthweight at delivery. The year of training of the resident that performed the ultrasound was recorded. Exclusion criteria included Diabetes mellitus and known fetal anomalies. RESULTS: Mean age was 28 years, parity zero to four, mean gestational age 38 weeks. There was an average over estimation of 64.8 grams. The difference between mean EFW and mean BWT was not significant (p = 0.067). The difference between mean EFW and mean BWT when calculated according to year of residency was not significant, p = 0.075 and 0.402 for junior and senior residents, respectively. CONCLUSION: There is good correlation between resident's ultrasonographic estimation of fetal weight and actual birthweight at the UHWI. There was no significant difference in correlation between senior and junior residents. Development in computer technology might contribute to decrease in the learning curve. PMID- 25117391 TI - Second Transurethral Resection of Bladder Tumour for the Treatment of Muscle invasive Bladder Tumours. AB - BACKGROUND: Exacerbations of Chronic Obstructive Pulmonary Disease (ECOPD) are a major problem worldwide and usually a leading cause for hospitalizations and in some cases, indication for invasive mechanical ventilation (IMV). OBJECTIVE: The aim of this study was to determine the length of stay in hospital and outcome of ECOPD patients. We compared the length of hospital stay in the medical ward, intensive care unit (ICU) departments and discharges during a period of six months. METHODS: This was an observational, longitudinal prospective study of 242 COPD patients that were admitted with COPD exacerbation. In each patient, acute physiology and chronic health evaluation (APACHE) II score and serial arterial blood gases (ABG) were measured upon and during admission. RESULTS: Eighty per cent (194) of 242 COPD patients were admitted to the medical department and most of them were discharged within five days. Forty-eight needed IMV and stayed in hospital more than ten days; overall mortality rate was about 5%. CONCLUSION: Most of the hospitalized patients with COPD exacerbation (60%) were discharged within five days, 20% needed IMV and stayed in hospital more than ten days. PMID- 25117390 TI - Hypothalamic-pituitary-ovarian Axis in Thyroid Dysfunction. AB - BACKGROUND: It has been established that thyroid dysfunction causes impairment of reproductive function. However, laboratory and human studies that associated this with female reproductive hormones are conflicting and data reporting the effects of thyroid dysfunction on reproductive organs are insufficient. AIM: This study investigated the effect of experimental hypothyroidism and hyperthyroidism on hypothalamic-pituitary-ovarian axis and reproductive organs morphometry and histology in female rats. METHODS: Laboratory animals were randomized into one of the three groups: control, carbimazole-induced hypothyroidism and levothyroxine induced hyperthyroidism. RESULTS: Organ morphometry and serum follicle stimulating hormone (FSH) were statistically comparable across all groups. Serum progesterone increased in hypothyroid rats but was reduced in hyperthyroid rats when compared with the control (p < 0.05). Body weight gain, serum luteinizing hormone and oestradiol were significantly reduced in both hypothyroid and hyperthyroid states when compared to the control. Hypothyroidism and hyperthyroidism also led to alterations in organ cytoarchitecture. CONCLUSION: Findings from this study suggest that impairment of reproductive function associated with thyroid dysfunction is attendant with derangement of hormonal milieu and alteration in reproductive organs cytoarchitecture. Luteinizing hormone and oestradiol are implicated. PMID- 25117392 TI - Evaluation of incidental thyroid cancer in patients with thyroidectomy. AB - OBJECTIVES: Variations such as communications between median nerve and musculocutaneous nerve or in their abnormal branching pattern constitute a major concern in clinical and surgical field. Knowledge of these variations not only provides the clinician with a proper interpretation of the case, but also minimizes the complication in surgical approaches in this region. METHOD: We examined 50 isolated upper limbs to investigate the possible incidences of various types of communications between these two neighbouring peripheral nerves. RESULT: Twenty-eight per cent of limbs were found to have communication between these two nerves. When categorized according to Venieratos and Anagnostopoulou's classification method, 11 out of 14 cases (79%) showed type I communications, two out of 14 (14%) showed type II and the remaining one (7%) showed type III communication pattern. CONCLUSION: Prior knowledge of communications between these two neighbouring nerves, both in terms of their incidences and pattern of communications, may be of considerable significance to neurologists and orthopaedicians in dealing with nerve entrapment syndromes in the upper limb of patients. PMID- 25117393 TI - A plea for more umbilical stomas in paediatric surgical practice. PMID- 25117394 TI - Incontinentia Pigmenti in 22-month Old Afro-Caribbean Fraternal Twin Girls. A Case Report. AB - Incontinentia pigmenti is a rare X-linked dominant condition characterized by cutaneous, neural, ocular and dental manifestations. The condition has mainly been reported in Caucasian females. The aim of this case report is to highlight the clinical presentation in Afro-Caribbean twin girls. The girls demonstrated abnormal hair distribution, pigmented limbs and torso, small conical or missing teeth with delayed dental eruption. PMID- 25117395 TI - Deep lobe parotid abscess with facial nerve palsy: a case report. AB - Acute suppurative sialadenitis mostly occurs in the parotid gland, while parotid abscesses principally arise in the superficial lobe. However, facial nerve palsy, secondary to parotid abscess, is rare. Predisposing factors for the ductally ascending infection are dehydration, xerogenic drugs and salivary gland diseases associated with ductal obstruction or reduced saliva secretion. Obstruction of Stensen's duct and diminished production of saliva are regarded as the promoting factors. Painful swelling of the preauricular region and cheek is the most familiar symptom of acute suppurative parotitis. The most common pathogens associated with acute bacterial infection are Staphylococcus aureus and anaerobes. We report a rare case of deep lobe parotid abscess with facial nerve palsy. Aside from adequate fluid hydration, good oral hygiene and treatment with empiric parenteral antibiotics, surgical treatment with drainage can provide a remedy for this disease. PMID- 25117396 TI - Metastatic tumour of spermatic cords, epididymis and seminiferous duct from gastric carcinoma. AB - Metastatic tumour of spermatic cords, epididymis and seminiferous duct from gastric carcinoma has been recently reported but rarely seen.A case of metastatic tumour from gastric carcinoma in a 50-year old man is herein reported. The initial diagnosis was thickening of both spermatic cords. Needle biopsy of the spermatic cord, testicle and epididymis was performed. Pathological findings showed a gastric signet ring cell carcinoma. Thus, double radical orchiectomy was performed and metastatic signet ring cell carcinoma of the spermatic cord and testis was diagnosed through histological xamination and immunohistochemistry. Physicians should be aware that gastric carcinoma is one of the possibilities for metastasis to the seminal duct. PMID- 25117397 TI - Treatment with acarbose in severe hypoglycaemia due to late dumping syndrome. AB - Dumping syndrome is a serious complication that may occur after gastric surgery in approximately 10% of patients in the 1990s. With the increasing number of patients undergoing bariatric surgery, the incidence of dumping syndrome is likely to increase in recent years. It is necessary for clinicians to recognize the syndrome and master its management. We present a case of recurrent loss of consciousness, which was finally accurately diagnosed as late dumping syndrome twelve years after subtotal gastrectomy and successfully treated with acarbose. A 66-year old lean male was found unconscious repeatedly within one year, oral glucose tolerance tests performed before and after acarbose treatment verified the diagnosis of late dumping syndrome. Hypoglycaemia can damage the body in acute and chronic form. Acarbose can be used as a successful treatment modality for reactive hypoglycaemia due to late dumping syndrome by influencing the release of hormone. PMID- 25117398 TI - Recurrent primary hydatid disease of the tibia. AB - Hydatid disease is caused by a cestode, Echinococcus. Its intermediate hosts are herbivores but humans can be accidental hosts. Hydatid disease is endemic in some parts of America, Australia, the Mediterranean region, Central Asia, and Central and Eastern Europe. The organs most frequently affected by Echinococcus are the liver and the lungs. Primary involvement of the skeleton is rare. Cases have been reported in the vertebrae, pelvis, humerus and femur. The location of hydatid cysts in the tibia is rarely described in the medical literature. We, herein, report a case of primary hydatid cyst of the tibia presenting with a pathologic fracture simulating benign bone cystic lesion. The diagnosis of hydatid bone disease was not suspected preoperatively. This case emphasizes the importance of considering hydatid disease in the differential diagnosis of cystic bone lesions, especially in individuals coming from regions where the disease is endemic. PMID- 25117399 TI - Chronic renal disease and reversible posterior leukoencephalopathy syndrome after liver transplantation. AB - This is a case report of a patient who developed chronic renal dysfunction and neurologic emergency with multiple cranial lesions after liver transplantation. Immune-complex glomerulonephritis was confirmed on the basis of histopathologic evaluation of the renal biopsy. According to clinical features and brain magnetic resonance imaging follow-up, neuroradiographic atypical reversible posterior leukoencephalopathy syndrome (RPLS) was finally diagnosed. PMID- 25117400 TI - Effects of the Etna uphill ultramarathon on energy cost and mechanics of running. AB - PURPOSE: To investigate the effects of an extreme uphill marathon on the mechanical parameters that are likely to affect the energy cost of running (Cr). METHODS: Eleven runners (27-59 y) participated in the Etna SuperMarathon (43 km, 0-3063 m above sea level). Anthropometric characteristics, maximal explosive power of the lower limb (Pmax), and maximal oxygen uptake were determined before the competition. In addition, before and immediately after the race, Cr, contact (tc) and aerial (ta) times, step frequency (f), and running velocity were measured at constant self-selected speed. Then, peak vertical ground-reaction force (Fmax), vertical downward displacement of the center of mass (Deltaz), leg length change (DeltaL), and vertical (kvert) and leg (kleg) stiffness were calculated. RESULTS: A direct relationship between Cr, measured before the race, and race time was shown (r=.61, P<.001). Cr increased significantly at the end of the race by 8.7%. Immediately after the race, the subjects showed significantly lower ta (-58.6%), f (-11.3%), Fmax (-17.6%), kvert (-45.6%), and kleg (-42.3%) and higher tc (+28.6%), Deltaz (+52.9%), and DeltaL (+44.5%) than before the race. The increase of Cr was associated with a decrement in Fmax (r=-.45), kvert (r=-.44), and kleg (r=-.51). Finally, an inverse relationship between Pmax measured before the race and DeltaCr during race was found (r=-.52). CONCLUSIONS: Lower Cr was related with better performance, and athletes characterized by the greater Pmax showed lower increases in Cr during the race. This suggests that specific power training of the lower limbs may lead to better performance in ultraendurance running competition. PMID- 25117401 TI - Development of casein microgels from cross-linking of casein micelles by genipin. AB - Casein micelles are porous colloidal particles, constituted of casein molecules, water, and minerals. The vulnerability of the supramolecular structure of casein micelles face to changes in the environmental conditions restrains their applications in other domains besides food. Thus, redesigning casein micelles is a challenge to create new functionalities for these biosourced particles. The objective of this work was to create stable casein microgels from casein micelles using a natural cross-linker, named genipin. Suspensions of purified casein micelles (25 g L(-1)) were mixed with genipin solutions to have final concentrations of 5, 10, and 20 mM genipin. Covalently linked casein microgels were formed via cross-linking of lysyl and arginyl residues of casein molecules. The reacted products exhibited blue color. The cross-linking reaction induced gradual changes on the colloidal properties of the particles. The casein microgels were smaller and more negatively charged and presented smoother surfaces than casein micelles. These results were explained based on the cross linking of free NH2 present in an external layer of kappa-casein. Light scattering and rheological measurements showed that the reaction between genipin and casein molecules was intramicellar, as one single population of particles was observed and the values of viscosity (and, consequently, the volume fraction of the particles) were reduced. Contrary to the casein micelles, the casein microgels were resistant to the presence of dissociating agents, e.g., citrate (calcium chelating) and urea, but swelled as a consequence of internal electrostatic repulsion and the disruption of hydrophobic interactions between protein chains. The casein microgels did not dissociate at the air-solution interface and formed solid-like interfaces rather than a viscoelastic gel. The potential use of casein microgels as adaptable nanocarriers is proposed in the article. PMID- 25117402 TI - DNA Commission of the International Society for Forensic Genetics: revised and extended guidelines for mitochondrial DNA typing. AB - The DNA Commission of the International Society of Forensic Genetics (ISFG) regularly publishes guidelines and recommendations concerning the application of DNA polymorphisms to the question of human identification. Previous recommendations published in 2000 addressed the analysis and interpretation of mitochondrial DNA (mtDNA) in forensic casework. While the foundations set forth in the earlier recommendations still apply, new approaches to the quality control, alignment and nomenclature of mitochondrial sequences, as well as the establishment of mtDNA reference population databases, have been developed. Here, we describe these developments and discuss their application to both mtDNA casework and mtDNA reference population databasing applications. While the generation of mtDNA for forensic casework has always been guided by specific standards, it is now well-established that data of the same quality are required for the mtDNA reference population data used to assess the statistical weight of the evidence. As a result, we introduce guidelines regarding sequence generation, as well as quality control measures based on the known worldwide mtDNA phylogeny, that can be applied to ensure the highest quality population data possible. For both casework and reference population databasing applications, the alignment and nomenclature of haplotypes is revised here and the phylogenetic alignment proffered as acceptable standard. In addition, the interpretation of heteroplasmy in the forensic context is updated, and the utility of alignment-free database searches for unbiased probability estimates is highlighted. Finally, we discuss statistical issues and define minimal standards for mtDNA database searches. PMID- 25117403 TI - Population data of 12 X-chromosome STR loci in Yanbian Korean samples from China. PMID- 25117405 TI - Thyrostimulin deficiency does not alter peripheral responses to acute inflammation-induced nonthyroidal illness. AB - Thyrostimulin, a putative glycoprotein hormone, comprises the subunits GPA2 and GPB5 and activates the TSH receptor (TSHR). The observation that proinflammatory cytokines stimulate GPB5 transcription suggested a role for thyrostimulin in the pathogenesis of nonthyroidal illness syndrome (NTIS). In the present study, we induced acute inflammation by LPS administration to GPB5(-/-) and WT mice to evaluate the role of thyrostimulin in peripheral thyroid hormone metabolism during NTIS. In addition to serum thyroid hormone concentrations, we studied mRNA expression and activity of deiodinase types I, II, and III (D1, D2, and D3) in peripheral T3 target tissues, including liver, muscle, and white and brown adipose tissue (WAT and BAT), of which the latter three express the TSHR. LPS decreased serum free (f)T4 and fT3 indexes to a similar extent in GPB5(-/-) and WT mice. Serum reverse (r)T3 did not change following LPS administration. LPS also induced significant alterations in tissue D1, D2, and D3 mRNA and activity levels, but only the LPS-induced increase in WAT D2 mRNA expression differed between GPB5(-/-) and WT mice. In conclusion, lacking GPB5 during acute illness does not affect the LPS-induced decrease of serum thyroid hormones while resulting in subtle changes in tissue D2 expression that are unlikely to be mediated via the TSHR. PMID- 25117404 TI - Vasodilator-stimulated phosphoprotein protects against vascular inflammation and insulin resistance. AB - Among the pleotropic effects of endothelial nitric oxide (NO) is protection against vascular inflammation during high-fat diet (HFD) feeding. The current work investigated the role of the enzyme vasodilatory-stimulated phosphoprotein (VASP) as a downstream mediator of the anti-inflammatory effect of NO signaling in vascular tissue. Relative to mice fed a low-fat diet (LFD), levels of VASP Ser(239) phosphorylation, a marker of VASP activation, were dramatically reduced in aortic tissue of mice with obesity induced by consuming a HFD. As reported previously, the effect of the HFD was associated with increased aortic inflammation, as measured by increased NF-kappaB-dependent gene expression, and reduced vascular insulin sensitivity (including insulin-stimulated phosphorylation of eNOS and Akt). These effects of the HFD were recapitulated by VASP knockout, implying a physiological role for VASP to constrain inflammatory signaling and thereby maintain vascular insulin sensitivity. Conversely, overexpression of VASP in endothelial cells blocked inflammation and insulin resistance induced by palmitate. The finding that transplantation of bone marrow from VASP-deficient donors into normal recipients does not recapitulate the vascular effects of whole body VASP deficiency suggests that the protective effects of this enzyme are not mediated in immune or other bone marrow-derived cells. These studies implicate VASP as a downstream mediator of the NO/cGMP pathway that is both necessary and sufficient to protect against vascular inflammation and insulin resistance. As such, this work identifies VASP as a potential therapeutic target in the treatment of obesity-related vascular dysfunction. PMID- 25117406 TI - Role of capsaicin-sensitive peripheral sensory neurons in anorexic responses to intravenous infusions of cholecystokinin, peptide YY-(3-36), and glucagon-like peptide-1 in rats. AB - Cholecystokinin (CCK)-induced suppression of feeding is mediated by vagal sensory neurons that are destroyed by the neurotoxin capsaicin (CAP). Here we determined whether CAP-sensitive neurons mediate anorexic responses to intravenous infusions of gut hormones peptide YY-(3-36) [PYY-(3-36)] and glucagon-like peptide-1 (GLP 1). Rats received three intraperitoneal injections of CAP or vehicle (VEH) in 24 h. After recovery, non-food-deprived rats received at dark onset a 3-h intravenous infusion of CCK-8 (5, 17 pmol.kg-1.min-1), PYY-(3-36) (5, 17, 50 pmol.kg-1.min-1), or GLP-1 (17, 50 pmol.kg-1.min-1). CCK-8 was much less effective in reducing food intake in CAP vs. VEH rats. CCK-8 at 5 and 17 pmol.kg 1.min-1 reduced food intake during the 3-h infusion period by 39 and 71% in VEH rats and 7 and 18% in CAP rats. In contrast, PYY-(3-36) and GLP-1 were similarly effective in reducing food intake in VEH and CAP rats. PYY-(3-36) at 5, 17, and 50 pmol.kg-1.min-1 reduced food intake during the 3-h infusion period by 15, 33, and 70% in VEH rats and 13, 30, and 33% in CAP rats. GLP-1 at 17 and 50 pmol.kg 1.min-1 reduced food intake during the 3-h infusion period by 48 and 60% in VEH rats and 30 and 52% in CAP rats. These results suggest that anorexic responses to PYY-(3-36) and GLP-1 are not primarily mediated by the CAP-sensitive peripheral sensory neurons (presumably vagal) that mediate CCK-8-induced anorexia. PMID- 25117407 TI - Stimulation of glucagon-like peptide-1 receptor through exendin-4 preserves myocardial performance and prevents cardiac remodeling in infarcted myocardium. AB - We have demonstrated that GLP-1 improved myocardial functional recovery in acute myocardial ischemic injury. However, whether stimulation of the GLP-1 receptor (GLP-1R) with exendin-4, a selective GLP-1R agonist, could initiate a protective effect in the heart remains to be determined. Mouse myocardial infarction (MI) was created by ligation of the left descending artery. After 48 h of MI, animals were divided into the following groups (n = 5-7/group): 1) sham (animals that underwent thoracotomy without ligation), 2) MI [animals that underwent MI and received a daily dose of intraperitoneal injection (ip) of saline]; and 3) MI + exendin-4 [infarcted mice that received injections of exendin-4 (0.1 mg/kg ip)]. Two weeks later, cardiac function was assessed by echocardiography and an isovolumetrically perfused heart. Compared with control MI hearts, stimulation of GLP-1R improved cardiac function, which was associated with attenuation of myocardial hypertrophy, the mitigation of interstitial fibrosis, and an increase in survival rate in post-MI hearts. Furthermore, H9c2 cardiomyoblasts were preconditioned with exendin-4 at a dose of 100 nmol/l and then subjected to hydrogen peroxide exposure at concentrations of 50 and 100 MUmol/l. The exendin-4 treatment decreased lactate dehydrogenase leakage and increased cell survival. Notably, this event was also associated with the reduction of cleaved caspase-3 and caspase-9 and attenuation of reactive oxygen species production. Exendin-4 treatments improved mitochondrial respiration and suppressed the opening of mitochondrial permeability transition pore and protected mitochondria function. Our results indicate that GLP-1R serves as a novel approach to eliciting cardioprotection and mitigating oxidative stress-induced injury. PMID- 25117408 TI - Hepatic portal vein denervation impairs oral glucose tolerance but not exenatide's effect on glycemia. AB - The hepatoportal area is an important glucohomeostatic metabolic sensor, sensing hypoglycemia, hyperglycemia, and hormones such as glucagon-like peptide-1 (GLP 1). We have reported previously that activation of hepatoportal sensors by intraportal infusion of glucose and GLP-1 or by subcutaneous administration of GLP-1 receptor activator exenatide and of intraportal glucose improved glycemia independent of corresponding changes in pancreatic hormones. It is not clear whether this effect is mediated via the portal vein (PV) or by direct action on the liver itself. To test whether receptors in the PV mediate exenatide's beneficial effect on glucose tolerance, we performed 1) paired oral glucose tolerance tests (OGTT) with and without exenatide and 2) intravenous glucose tolerance tests before and after PV denervation in canines. Denervation of the portal vein affected oral glucose tolerance; post-denervation (POST-DEN) OGTT glucose and insulin AUC were 50% higher than before denervation (P = 0.01). However, portal denervation did not impair exenatide's effect to improve oral glucose tolerance (exenatide effect: 48 +/- 12 mmol.l-1.min before vs. 64 +/- 26 mmol.l-1.min after, P = 0.67). There were no changes in insulin sensitivity or secretion during IVGTTs. Portal vein sensing might play a role in controlling oral glucose tolerance during physiological conditions but not in pharmacological activation of GLP-1 receptors by exenatide. PMID- 25117410 TI - Role of STAT5 and epigenetics in lactation-associated upregulation of multidrug transporter ABCG2 in the mammary gland. AB - The multidrug resistance efflux transporter ATP-binding cassette subfamily G member 2 (ABCG2) is not only overexpressed in certain drug-resistant cancers but is also highly expressed in the mammary gland during lactation, carrying xenobiotics and nutrients into milk. We sought to investigate the molecular mechanisms involved in the upregulation of ABCG2 during lactation. Expression profiling of different mouse Abcg2 mRNA isoforms (E1a, E1b, and E1c) revealed that E1b is predominantly expressed and induced in the lactating mouse mammary gland. Despite this induction, analyses of CpG methylation status and published ChIP-seq datasets reveal that E1b promoter sequences in the virgin gland are already hypomethylated and marked with the open chromatin histone mark H3K4me2. Using a forced-weaning model to shut down lactation, we found that within 24 h there was a significant reduction in Abcg2 mRNA expression and a loss of signal transducer and activator of transcription-5 (STAT5) occupancy at the mouse Abcg2 gene. Luciferase reporter assays further showed that some of these STAT5-binding regions that contained interferon-gamma-activated sequence (GAS) motifs function as an enhancer after prolactin treatment. We conclude that Abcg2 is already poised for expression in the virgin mammary gland and that STAT5 plays an important role in Abcg2 expression during lactation. PMID- 25117409 TI - Partial blockade of nicotinic acetylcholine receptors improves the counterregulatory response to hypoglycemia in recurrently hypoglycemic rats. AB - Recurrent exposure to hypoglycemia can impair the normal counterregulatory hormonal responses that guard against hypoglycemia, leading to hypoglycemia unawareness. This pathological condition known as hypoglycemia-associated autonomic failure (HAAF) is the main adverse consequence that prevents individuals with type 1 diabetes mellitus from attaining the long-term health benefits of tight glycemic control. The underlying molecular mechanisms responsible for the progressive loss of the epinephrine response to subsequent bouts of hypoglycemia, a hallmark sign of HAAF, are largely unknown. Normally, hypoglycemia triggers both the release and biosynthesis of epinephrine through activation of nicotinic acetylcholine receptors (nAChR) on the adrenal glands. We hypothesize that excessive cholinergic stimulation may contribute to impaired counterregulation. Here, we tested whether administration of the nAChR partial agonist cytisine to reduce postganglionic synaptic activity can preserve the counterregulatory hormone responses in an animal model of HAAF. Compared with nicotine, cytisine has limited efficacy to activate nAChRs and stimulate epinephrine release and synthesis. We evaluated adrenal catecholamine production and secretion in nondiabetic rats subjected to two daily episodes of hypoglycemia for 3 days, followed by a hyperinsulinemic hypoglycemic clamp on day 4. Recurrent hypoglycemia decreased epinephrine responses, and this was associated with suppressed TH mRNA induction (a measure of adrenal catecholamine synthetic capacity). Treatment with cytisine improved glucagon responses as well as epinephrine release and production in recurrently hypoglycemic animals. These data suggest that pharmacological manipulation of ganglionic nAChRs may be promising as a translational adjunctive therapy to avoid HAAF in type 1 diabetes mellitus. PMID- 25117411 TI - The effect of estrogen on bone requires ERalpha in nonhematopoietic cells but is enhanced by ERalpha in hematopoietic cells. AB - The effects of estrogen on bone are mediated mainly via estrogen receptor (ER)alpha. ERalpha in osteoclasts (hematopoietic origin) is involved in the trabecular bone-sparing effects of estrogen, but conflicting data are reported on the role of ERalpha in osteoblast lineage cells (nonhematopoietic origin) for bone metabolism. Because Cre-mediated cell-specific gene inactivation used in previous studies might be confounded by nonspecific and/or incomplete cell specific ERalpha deletion, we herein used an alternative approach to determine the relative importance of ERalpha in hematopoietic (HC) and nonhematopoietic cells (NHC) for bone mass. Chimeric mice with selective inactivation of ERalpha in HC or NHC were created by bone marrow transplantations of wild-type (WT) and ERalpha-knockout (ERalpha(-/-)) mice. Estradiol treatment increased both trabecular and cortical bone mass in ovariectomized WT/WT (defined as recipient/donor) and WT/ERalpha(-/-) mice but not in ERalpha(-/-)/WT or ERalpha( /-)/ERalpha(-/-) mice. However, estradiol effects on both bone compartments were reduced (~50%) in WT/ERalpha(-/-) mice compared with WT/WT mice. The effects of estradiol on fat mass and B lymphopoiesis required ERalpha specifically in NHC and HC, respectively. In conclusion, ERalpha in NHC is required for the effects of estrogen on both trabecular and cortical bone, but these effects are enhanced by ERalpha in HC. PMID- 25117413 TI - Interventions for congenital talipes equinovarus (clubfoot). AB - BACKGROUND: Congenital talipes equinovarus (CTEV), which is also known as clubfoot, is a common congenital orthopaedic condition characterised by an excessively turned in foot (equinovarus) and high medial longitudinal arch (cavus). If left untreated it can result in long-term disability, deformity and pain. Interventions can be conservative (such as splinting or stretching) or surgical. The review was first published in 2012 and we reviewed new searches in 2013 (update published 2014). OBJECTIVES: To evaluate the effectiveness of interventions for CTEV. SEARCH METHODS: On 29 April 2013, we searched CENTRAL (2013, Issue 3 in The Cochrane Library), MEDLINE (January 1966 to April 2013), EMBASE (January 1980 to April 2013), CINAHL Plus (January 1937 to April 2013), AMED (1985 to April 2013), and the Physiotherapy Evidence Database (PEDro to April 2013). We also searched for ongoing trials in the WHO International Clinical Trials Registry Platform (2006 to July 2013) and ClinicalTrials.gov (to November 2013). We checked the references of included studies. We searched NHSEED, DARE and HTA for information for inclusion in the Discussion. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating interventions for CTEV. Participants were people of all ages with CTEV of either one or both feet. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias in included trials and extracted the data. We contacted authors of included trials for missing information. We collected adverse event information from trials when it was available. MAIN RESULTS: We identified 14 trials in which there were 607 participants; one of the trials was newly included at this 2014 update. The use of different outcome measures prevented pooling of data for meta-analysis even when interventions and participants were comparable. All trials displayed bias in four or more areas. One trial reported on the primary outcome of function, though raw data were not available to be analysed. We were able to analyse data on foot alignment (Pirani score), a secondary outcome, from three trials. Two of the trials involved participants at initial presentation. One reported that the Ponseti technique significantly improved foot alignment compared to the Kite technique. After 10 weeks of serial casting, the average total Pirani score of the Ponseti group was 1.15 (95% confidence interval (CI) 0.98 to 1.32) lower than that of the Kite group. The second trial found the Ponseti technique to be superior to a traditional technique, with average total Pirani scores of the Ponseti participants 1.50 lower (95% CI 0.72 to 2.28) after serial casting and Achilles tenotomy. A trial in which the type of presentation was not reported found no difference between an accelerated Ponseti or standard Ponseti treatment. At the end of serial casting, the average total Pirani scores in the standard group were 0.31 lower (95% CI -0.40 to 1.02) than the accelerated group. Two trials in initial cases found relapse following Ponseti treatment was more likely to be corrected with further serial casting compared to the Kite groups which more often required major surgery (risk difference 25% and 50%). There is a lack of evidence for different plaster casting products, the addition of botulinum toxin A during the Ponseti technique, different types of major foot surgery, continuous passive motion treatment following major foot surgery, or treatment of relapsed or neglected cases of CTEV. Most trials did not report on adverse events. In trials evaluating serial casting techniques, adverse events included cast slippage (needing replacement), plaster sores (pressure areas) and skin irritation. Adverse events following surgical procedures included infection and the need for skin grafting. AUTHORS' CONCLUSIONS: From the limited evidence available, the Ponseti technique produced significantly better short-term foot alignment compared to the Kite technique and compared to a traditional technique. The quality of this evidence was low to very low. An accelerated Ponseti technique may be as effective as a standard technique, according to moderate quality evidence. Relapse following the Kite technique more often led to major surgery compared to relapse following the Ponseti technique. We could draw no conclusions from other included trials because of the limited use of validated outcome measures and lack of available raw data. Future randomised controlled trials should address these issues. PMID- 25117414 TI - Melatonin Can Be Used to Treat Childhood Breath-Holding Spells. PMID- 25117412 TI - Differential effects of c-Src and c-Yes on the endocytic vesicle-mediated trafficking events at the Sertoli cell blood-testis barrier: an in vitro study. AB - The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. However, it undergoes cyclic restructuring during the epithelial cycle of spermatogenesis in which the "old" BTB located above the preleptotene spermatocytes being transported across the immunological barrier is "disassembled," whereas the "new" BTB found behind these germ cells is rapidly "reassembled," i.e., mediated by endocytic vesicle-mediated protein trafficking events. Thus, the immunological barrier is maintained when preleptotene spermatocytes connected in clones via intercellular bridges are transported across the BTB. Yet the underlying mechanism(s) in particular the involving regulatory molecules that coordinate these events remains unknown. We hypothesized that c-Src and c-Yes might work in contrasting roles in endocytic vesicle-mediated trafficking, serving as molecular switches, to effectively disassemble and reassemble the old and the new BTB, respectively, to facilitate preleptotene spermatocyte transport across the BTB. Following siRNA-mediated specific knockdown of c-Src or c-Yes in Sertoli cells, we utilized biochemical assays to assess the changes in protein endocytosis, recycling, degradation and phagocytosis. c-Yes was found to promote endocytosed integral membrane BTB proteins to the pathway of transcytosis and recycling so that internalized proteins could be effectively used to assemble new BTB from the disassembling old BTB, whereas c-Src promotes endocytosed Sertoli cell BTB proteins to endosome mediated protein degradation for the degeneration of the old BTB. By using fluorescence beads mimicking apoptotic germ cells, Sertoli cells were found to engulf beads via c-Src-mediated phagocytosis. A hypothetical model that serves as the framework for future investigation is thus proposed. PMID- 25117415 TI - Serum N-Terminal Pro-B-Type Natriuretic Peptide (NTproBNP) Levels Are Elevated During the Acute Phase of Acute Encephalopathy-Associated Virus Infection. AB - Acute virus-associated encephalopathy induces seizures. Serum N-terminal pro-B type natriuretic peptide (NTproBNP) levels are elevated following febrile and afebrile seizures. However, the role of NTproBNP in acute virus-associated encephalopathy pathology is unknown. We enrolled 10 patients with acute virus associated encephalopathy and convulsions (E group: 7 boys, 3 girls; median age, 3.10 +/- 1.92 years) and 130 patients with febrile seizure (FS group: 80 boys, 50 girls; median age, 3.23 +/- 2.44 years). The E group had significantly higher NTproBNP levels (345 +/- 141 pg/mL) compared with the FS group (166 +/- 228 pg/mL) (P < .0005). Furthermore, subjects with prolonged seizure within the E group had significantly higher NTproBNP levels (303 +/- 107 pg/mL) compared with subjects with prolonged seizure within the FS group (134 +/- 100 pg/mL) (P < .005). Our findings suggest that serum NTproBNP levels are increased during the acute phase of acute virus-associated encephalopathy associated with convulsion. PMID- 25117416 TI - Sturge Weber-Like Gyral Calcification Seen in Tuberous Sclerosis Complex 1. AB - A 10-year-old girl presented with poorly controlled epilepsy. On evaluation, she had microcephaly, neuro-cutaneous stigmata of tuberous sclerosis complex, profound mental retardation, and spastic hemiparesis. Computed tomography (CT) revealed a calcified subependymal nodule and extensive left gyral calcification of the temporal, parietal, and occipital regions with unilateral cerebral atrophy, radiologic features usually seen in Sturge Weber syndrome. Magnetic resonance imaging (MRI) revealed absence of tubers, enlarged choroid plexus, or leptomeningeal angiomas, thus excluding type 3 Sturge Weber syndrome. The genotype was a heterozygous mutation in exon 18 of the tuberous sclerosis type 1 gene (c.2293C>T p.Q765X). A comparison of previously reported 7 cases of Sturge Weber syndrome and tuberous sclerosis complex was made. This revealed 4 actual double phakomatoses (clinical, radiologic, or genetic phenotypes) and 3 cases with clinical phenotype of tuberous sclerosis and gyral calcifications within tubers simulating the radiologic picture of Sturge Weber syndrome. PMID- 25117417 TI - Impact of rotavirus vaccine introduction on rotavirus-associated seizures and a related possible mechanism. AB - To determine whether clinical features of rotavirus-associated seizures have been altered by rotavirus vaccination, we compared clinical and laboratory data of 2 groups of patients with rotavirus-associated seizures: pre- and post-vaccine introduction groups. The seizure characteristics differed significantly between the groups, with a lower incidence of fever at seizure onset, longer interval between the onset of gastroenteritis and seizures, and more frequent seizures in the postintroduction group. These characteristics may suggest that seizure susceptibility was increased in the postintroduction group. Based on the lower serum Cl(-) (102.1 +/- 4.1 vs 98.2 +/- 3.2 mg/dL; P < .01) and Ca(2+) levels (9.2 +/- 0.4 vs 9.0 +/- 0.3 mg/dL; P = .12) in the postintroduction group, we propose that a change in the subjects' susceptibility to the rotavirus enterotoxin may have played a role in increasing the seizure susceptibility in this group. Our results suggest that a rotavirus vaccination program may modulate the manifestations of rotavirus-associated seizures. PMID- 25117419 TI - Evaluation of basal ganglia and thalamic inflammation in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection and tourette syndrome: a positron emission tomographic (PET) study using 11C-[R] PK11195. AB - We applied PET scanning with (11)C-[R]-PK11195 (PK) to evaluate neuroinflammatory changes in basal ganglia and thalamus in children with clinically diagnosed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) and Tourette syndrome. Seventeen children with PANDAS (mean age: 11.4 +/- 2.6 years; 13 males), 12 with Tourette syndrome (mean age: 11.0 +/- 3.0 years; 10 males), and 15 normal adults (mean age: 28.7 +/- 7.9 years; 8 males) underwent dynamic PK PET imaging and binding potential, a measure of ligand-TSPO receptor (expressed by activated microglia) binding, was calculated for basal ganglia and thalamus. Binding potential values, suggesting underlying activated microglia-mediated neuroinflammation, were found to be increased in bilateral caudate and bilateral lentiform nucleus in the PANDAS group and in bilateral caudate nuclei only in the Tourette syndrome group, compared to control group. These differences in the pattern and extent of neuroinflammation also signify a possible difference in pathophysiological etiology between PANDAS and Tourette syndrome patients. PMID- 25117420 TI - A 5-year-old male child with late infantile metachromatic leukodystrophy: a case report. AB - Metachromatic leukodystrophy is a rare disorder of myelin metabolism. This degenerative disorder results from the accumulation of cerebroside sulfatide within the myelin sheath of central and peripheral nervous system, due to deficiency of aryl sulfatase A enzyme. We report a 5-year-old male child, who presented with regression of milestones, recurrent seizures and spasticity from second year of life. Initially neurodegenerative disorder was considered and the case was investigated with neuroimaging and enzyme levels. Computed tomography (CT) of the brain showed hypodensities in the corpus callosum and bilateral periventricular and deep cerebral white matter suggestive of neurodegenerative disorder. Subsequently, magnetic resonance imaging (MRI) of the brain was done, which showed symmetrical hyperintensities in the periventricular white matter with classical sparing of subcortical "U" fibers. The beta-galactosidase enzyme activity was normal; however, the activity of aryl sulfatase A enzyme was undetectable, confirming the diagnosis of late infantile variant of metachromatic leukodystrophy. PMID- 25117418 TI - Perinatal medical variables predict executive function within a sample of preschoolers born very low birth weight. AB - The goal was to identify perinatal predictors of early executive dysfunction in preschoolers born very low birth weight. Fifty-seven preschoolers completed 3 executive function tasks: Dimensional Change Card Sort-Separated (inhibition, working memory, and cognitive flexibility), Bear Dragon (inhibition and working memory), and Gift Delay Open (inhibition). Relationships between executive function and perinatal medical severity factors (gestational age, days on ventilation, size for gestational age, maternal steroids, and number of surgeries) and chronological age were investigated by multiple linear regression and logistic regression. Different perinatal medical severity factors were predictive of executive function tasks, with gestational age predicting Bear Dragon and Gift Open; and number of surgeries and maternal steroids predicting performance on Dimensional Change Card Sort-Separated. By understanding the relationship between perinatal medical severity factors and preschool executive outcomes, we can identify children at highest risk for future executive dysfunction, thereby focusing targeted early intervention services. PMID- 25117421 TI - Cluster stability as a new method to assess changes in performance and its determinant factors over a season in young swimmers. AB - PURPOSE: To apply a new method to identify, classify, and follow up young swimmers based on their performance and its determinant factors over a season and analyze the swimmers' stability over a competitive season with that method. METHODS: Fifteen boys and 18 girls (11.8+/-0.7 y) part of a national talent identification scheme were evaluated at 3 different moments of a competitive season. Performance (ie, official 100-m freestyle race time), arm span, chest perimeter, stroke length, swimming velocity, speed fluctuation, coefficient of active drag, propelling efficiency, and stroke index were selected as variables. Hierarchical and k-means cluster analysis were computed. RESULTS: Data suggested a 3-cluster solution, splitting the swimmers according to their performance in all 3 moments. Cluster 1 was related to better performances (talented swimmers), cluster 2 to poor performances (nonproficient swimmers), and cluster 3 to average performance (proficient swimmers) in all moments. Stepwise discriminant analysis revealed that 100%, 94%, and 85% of original groups were correctly classified for the 1st, 2nd, and 3rd evaluation moments, respectively (0.11<=Lambda<=0.80; 5.64<=chi2<=63.40; 0.00195%. Our results demonstrate the suitability of orbitally-shaken bioreactors for the scaled-up cultivation of plant cell suspension cultures and provide a strategy for the efficient purification of antibodies from the BY-2 culture medium. PMID- 25117429 TI - The relationship of training load to physical-capacity changes during international tours in high-performance junior tennis players. AB - PURPOSE: Given the travel that punctuates junior tennis development, an understanding of the changes in fitness owing to touring and the association between training loads (TLs) and fitness on return is vital. The authors investigated physical-capacity changes from pretour to posttour, determining if those changes were related to the TL of athletes on tour. METHODS: Thirty junior athletes completed fitness testing before and after 4-wk tours. Testing included double-leg countermovement jump (CMJ), dominant single-leg and nondominant single leg CMJ, speed (5, 10, 20 m), modified 5-0-5 agility (left and right), 10 * 20-m repeated-sprint ability (RSA), and multistage fitness tests. Repeated-measures ANOVAs determined physical-capacity change, with effect-size analysis establishing the magnitude of change. To avoid regression toward the mean, a 1/3 split technique was implemented for comparative analysis (high to low TLs). RESULTS: Moderate effects (d=0.50-0.70) for reductions of up to 3.6% in 5-, 10-, and 20-m speeds were observed. However, all remaining changes were only of trivial to small magnitude (d<0.40). Closer analysis of the interaction between TL and physical capacities (1/3-split) revealed that subjects who completed the greatest amount of total and tennis TL returned with a greater decline in speed and aerobic capacities (d>0.80). Furthermore, it was observed that match load dictates on- and off-court TL, with an increase in matches won understandably stunting exposure to off-court TL. CONCLUSIONS: Specific training should be prescribed on tour to maintain speed characteristics over a 4-wk international tour. On-tour training schedules should be carefully monitored to maximize specific TL exposure after losses on tour. PMID- 25117426 TI - CYP3A5 genotype impacts maraviroc concentrations in healthy volunteers. AB - CYP3A5 plays a prominent role in the metabolism of maraviroc, an approved drug for human immunodeficiency virus (HIV)-1 treatment and a candidate for HIV-1 prevention. We studied the effect of the CYP3A5 genotype on pharmacokinetics of maraviroc and a primary CYP3A5-dependent metabolite of maraviroc denoted as metabolite 1 (M1). Volunteers were screened for health status and CYP3A5 genotype (wild-type allele *1 and dysfunctional alleles *2, *3, *6, and *7) to obtain 24 evaluable subjects in three groups (n = 8 each): homozygous dysfunctional (two dysfunctional alleles), heterozygous (one *1 allele and one dysfunctional allele), and homozygous wild-type (two *1 alleles). Subjects received 300 mg maraviroc orally followed by blood collection for 32 hours. The homozygous wild type group exhibited lower mean plasma maraviroc concentrations at almost all sampling times. The median (interquartile range) maraviroc area under the plasma concentration-time curves from time 0 to infinity (AUC0-inf) were 2099 (1422 2568) ng?h/ml, 1761 (931-2640) ng?h/ml, and 1238 (1065-1407) ng?h/ml for the homozygous dysfunctional, heterozygous, and homozygous wild-type groups, respectively. The homozygous wild-type group had 41% lower maraviroc AUC0-inf and 66% higher apparent clearance compared with the homozygous dysfunctional group (P = 0.02). The AUC0-inf ratios of maraviroc to M1 in heterozygous and homozygous wild-type subjects were lower by 51 and 64% relative to the homozygous dysfunctional group, respectively (P < 0.001). In conclusion, the lower maraviroc concentrations in the homozygous wild-type group indicate that maraviroc may be underdosed in people homozygous for the CYP3A5*1 allele, including almost one half of African Americans. PMID- 25117430 TI - Draft genome sequence of Rhodomicrobium udaipurense JA643T with special reference to hopanoid biosynthesis. AB - Hopanoids are present in vast amounts as integral components of bacteria and plants with their primary function to strengthen rigidity of the plasma membrane. To establish their roles more precisely, we conducted sequencing of the whole genome of Rhodomicrobium udaipurense JA643(T) isolated from a fresh water stream of Udaipur in Himachal Pradesh, India, by using the Illumina HiSeq pair end chemistry of 2 * 100 bp platform. Determined genome showed a high degree of similarity to the genome of R. vannielii ATCC17100(T) and the 13.7 million reads generated a sequence of 3,649,277 bp possessing 3,611 putative genes. The genomic data were subsequently investigated with respect to genes involved in various features. The machinery required for the degradation of aromatic compounds and resistance to solvents as well as all that required for photosynthesis are present in this organism. Also, through extensive functional annotation, 18 genes involved in the biosynthesis of hopanoids are predicted, namely those responsible for the synthesis of diploptene, diplopterol, adenosylhopane, ribosylhopane, aminobacteriohopanetriol, glycosyl group containing hopanoids and unsaturated hopanoids. The hopanoid biosynthetic pathway was then inferred based on the genes identified and through experimental validation of individual hopanoid molecules. The genome data of R. udaipurense JA643(T) will be useful in understanding the functional features of hopanoids in this bacterium. PMID- 25117431 TI - Anthropometric and physiological profiling of youth soccer goalkeepers. AB - Studies focused on position-related characteristics of young soccer players often ignore the goalkeepers. The aim of this study was to examine the effect of playing position on anthropometry, physiological attributes, soccer skills, and goal orientation across adolescence. One hundred forty-five soccer players age 11 19 y were assessed in training experience, body size, maturation, physiological parameters, soccer skills, and goal orientation. Factorial ANOVA was used to test the effect of age group, playing position, and respective interaction terms, while analysis of variance was used to compare goalkeepers vs outfielders in middle (under 13 [U-13] and U-15) and late (U-17 and U-19) adolescence. Discriminant analysis was used to identify the variables that contributed to explaining playing positions. Age group was a consistent source of variation for all variables except task and ego orientations. Fat mass, agility, endurance, dribbling speed, shooting accuracy, and passing were affected by the gradient derived from the classification between goalkeepers and outfielders. It was possible to correctly classify the playing position based on fat-free mass and 3 manipulative skills in younger players and on 4 skills in U-17 and U-19 soccer players. Future research should include longitudinal information to improve our understanding of the factors that contribute to distinguish goalkeepers from outfielders. PMID- 25117433 TI - Effects of Sprint Training With or Without Ball Carry in Elite Rugby Players. AB - PURPOSE: To compare the effects of sprint training with or without ball carry on the sprint performance of elite rugby league players. METHODS: Twenty-four elite rugby league players were divided into a ball-carry group (BC; n = 12) and a no ball-carry group (NBC; n = 12). The players of the BC group were required to catch and carry the ball under 1 arm during each sprint, whereas the NBC group performed sprints without carrying a ball. The 8-wk training intervention took place during the precompetitive phase of the season and consisted of 2 sessions/wk. Sprint performance was measured before and after the training intervention with 40-m linear sprints performed under 2 conditions: with and without ball carry. Split times of 10, 20, and 40 m were recorded for further analysis. A 3-way (group * time * condition) factorial ANOVA was performed to compare changes in sprint performance with and without the ball, before and after the training intervention for both BC and NBC training groups Results: The BC and NBC groups experienced similar improvements in 10-, 20-, and 40-m sprint times and accelerations, regardless of the condition under which the sprint tests were performed (P = .19). CONCLUSIONS: Sprint training while carrying a rugby ball is as effective as sprint training without carrying a rugby ball for improving the sprint performance of elite rugby league players. PMID- 25117432 TI - Molecular signaling network motifs provide a mechanistic basis for cellular threshold responses. AB - BACKGROUND: Increasingly, there is a move toward using in vitro toxicity testing to assess human health risk due to chemical exposure. As with in vivo toxicity testing, an important question for in vitro results is whether there are thresholds for adverse cellular responses. Empirical evaluations may show consistency with thresholds, but the main evidence has to come from mechanistic considerations. OBJECTIVES: Cellular response behaviors depend on the molecular pathway and circuitry in the cell and the manner in which chemicals perturb these circuits. Understanding circuit structures that are inherently capable of resisting small perturbations and producing threshold responses is an important step towards mechanistically interpreting in vitro testing data. METHODS: Here we have examined dose-response characteristics for several biochemical network motifs. These network motifs are basic building blocks of molecular circuits underpinning a variety of cellular functions, including adaptation, homeostasis, proliferation, differentiation, and apoptosis. For each motif, we present biological examples and models to illustrate how thresholds arise from specific network structures. DISCUSSION AND CONCLUSION: Integral feedback, feedforward, and transcritical bifurcation motifs can generate thresholds. Other motifs (e.g., proportional feedback and ultrasensitivity)produce responses where the slope in the low-dose region is small and stays close to the baseline. Feedforward control may lead to nonmonotonic or hormetic responses. We conclude that network motifs provide a basis for understanding thresholds for cellular responses. Computational pathway modeling of these motifs and their combinations occurring in molecular signaling networks will be a key element in new risk assessment approaches based on in vitro cellular assays. PMID- 25117435 TI - Time-resolved infrared spectroscopic studies of ligand dynamics in the active site from cytochrome c oxidase. AB - The catalytic site of heme-copper oxidases encompasses two close-lying ligand binding sites: the heme, where oxygen is bound and reduced and the CuB atom, which acts as ligand entry and release port. Diatomic gaseous ligands with a dipole moment, such as the signaling molecules carbon monoxide (CO) and nitric oxide (NO), carry clear infrared spectroscopic signatures in the different states that allow characterization of the dynamics of ligand transfer within, into and out of the active site using time-resolved infrared spectroscopy. We review the nature and diversity of these processes that have in particular been characterized with CO as ligand and which take place on time scales ranging from femtoseconds to milliseconds. These studies have advanced our understanding of the functional ligand pathways and reactivity in enzymes and more globally represent intriguing model systems for mechanisms of ligand motion in a confined protein environment. This article is part of a Special Issue entitled: Vibrational spectroscopies and bioenergetic systems. PMID- 25117436 TI - Reliability and validity of a new variable-power performance test in road cyclists. AB - CONTEXT: Road cycle racing is characterized by significant variability in exercise intensity. Existing protocols attempting to model this aspect display inadequate variation in power output. Furthermore, the reliability of protocols representative of road cycle racing is not well known. There are also minimal data regarding the physiological parameters that best predict performance during variable-power cycling. PURPOSE: To determine the reliability of mean power output during a new test of variable-power cycling and establish the relationship between physiological attributes typically measured during an incremental exercise test and performance during the variable-power cycling test (VCT). METHODS: Fifteen trained male cyclists (mean +/- SD age 33 +/- 6.5 y, VO2max 57.9 +/- 4.8 mL . kg-1 . min-1) performed an incremental exercise test to exhaustion for determination of physiological attributes, 2 VCTs (plus familiarization), and a 30-km time trial. The VCT was modeled on data from elite men's road racing and included significant variation in power output. RESULTS: Mean power output during the VCT showed good reliability (r = .92, CV% = 1.98). Relative power during the self-paced sections of the VCT was most correlated with maximal aerobic power (r = .79) and power at the second ventilatory threshold (r = .69). Blood lactate concentration showed poor reliability between trials (CV% = 13.93%). CONCLUSIONS: This study has demonstrated a new reliable protocol simulating the stochastic nature of road cycling races. Further research is needed to determine which factors predict performance during variable-power cycling and the validity of the test in monitoring longitudinal changes in cycling performance. PMID- 25117434 TI - Protein as chemical cue: non-nutritional growth enhancement by exogenous protein in Pseudomonas putida KT2440. AB - Research pertaining to microbe-microbe and microbe-plant interactions has been largely limited to small molecules like quorum sensing chemicals. However, a few recent reports have indicated the role of complex molecules like proteins and polysaccharides in microbial communication. Here we demonstrate that exogenous proteins present in culture media can considerably accelerate the growth of Pseudomonas putida KT2440, even when such proteins are not internalized by the cells. The growth enhancement is observed when the exogenous protein is not used as a source of carbon or nitrogen. The data show non-specific nature of the protein inducing growth; growth enhancement was observed irrespective of the protein type. It is shown that growth enhancement is mediated via increased siderophore secretion in response to the exogenous protein, leading to better iron uptake. We highlight the ecological significance of the observation and hypothesize that exogenous proteins serve as chemical cues in the case of P.putida and are perceived as indicator of the presence of competitors in the environment. It is argued that enhanced siderophore secretion in response to exogenous protein helps P.putida establish numerical superiority over competitors by way of enhanced iron assimilation and quicker utilization of aromatic substrates. PMID- 25117437 TI - Health Promotion International - maintaining our vision for the future. PMID- 25117438 TI - A genetic screen in Drosophila for regulators of human prostate cancer progression. AB - To uncover the mechanism by which human prostate cancer progresses, we performed a genetic screen for regulators of human prostate cancer progression using the Drosophila accessory gland, a functional homolog of the mammalian prostate. Cell growth and migration of secondary cells in the adult male accessory gland were found to be regulated by paired, N-cadherin, and E-cadherin, which are Drosophila homologues of regulators of human prostate cancer progression. Using this screening system, we also identified three genes that promoted growth and migration of secondary cells in the accessory gland. The human homologues of these candidate genes - MRGBP, CNPY2, and MEP1A - were found to be expressed in human prostate cancer model cells and to promote replication and invasiveness in these cells. These findings suggest that the development of the Drosophila accessory gland and human prostate cancer cell growth and invasion are partly regulated through a common mechanism. The screening system using the Drosophila accessory gland can be a useful tool for uncovering the mechanisms of human prostate cancer progression. PMID- 25117439 TI - Axl is a novel target of withaferin A in the induction of apoptosis and the suppression of invasion. AB - Withaferin A, a withanolide derived from the medicinal plant Withania somnifera, has been reported to exhibit anti-tumorigenic activity against various cancer cells. In this study, we show that withaferin A inhibits the constitutive and recombinant human growth-arrest-specific protein 6 (rhGas6)-induced phosphorylation of Axl and STAT3. In addition, withaferin A also induces the down regulation of Axl protein expression in a lysosome-dependent manner and inhibits rhGas6-induced wound healing and cell migration. Furthermore, the overexpression of Axl attenuates withaferin A-induced apoptosis. Taken together, the data from the present study indicate that the withaferin A-mediated down-regulation of the Gas6/Axl signaling pathway mediates the inhibition of cell migration and the induction of apoptosis. PMID- 25117441 TI - Introducing transglycosylation activity in Bacillus licheniformis alpha-amylase by replacement of His235 with Glu. AB - To understand the role of His and Glu in the catalytic activity of Bacillus licheniformis alpha-amylase (BLA), His235 was replaced with Glu. The mutant enzyme, H235E, was characterized in terms of its mode of action using labeled and unlabeled maltooctaose (Glc8). H235E predominantly produced maltotridecaose (Glc13) from Glc8, exhibiting high substrate transglycosylation activity, with Km=0.38mM and kcat/Km=20.58mM(-1)s(-1) for hydrolysis, and Km2=18.38mM and kcat2/Km2=2.57mM(-1)s(-1) for transglycosylation, while the wild-type BLA exhibited high hydrolysis activity exclusively. Glu235-located on a wide open groove near subsite +1-is likely involved in transglycosylation via formation of an alpha-1,4-glycosidic linkage and may recognize and stabilize the non-reducing end glucose of the acceptor molecule. PMID- 25117440 TI - Ambra1 modulates starvation-induced autophagy through AMPK signaling pathway in cardiomyocytes. AB - Recent research has revealed a role for Ambra1, an autophagy-related gene-related (ATG) protein, in the autophagic pro-survival response, and Ambra1 has been shown to regulate Beclin1 and Beclin1-dependent autophagy in embryonic stem cells and cancer cells. However, whether Ambra1 plays an important role in the autophagy pathway in cardiomyocytes is unknown. In this study, we hypothesized that Ambra1 is an important regulator of autophagy and apoptosis in cardiomyocytes. To test this hypothesis, we confirmed autophagic activity in serum-starved cardiomyocytes by assessing endogenous microtubule-associated protein 1 light chain 3 (LC3) localization, the presence of autophagosomes and LC3 protein levels. Cell apoptosis and viability were measured by annexin-V and PI staining and MTT assays. We determined that serum deprivation-induced autophagy was associated with Ambra1 upregulation in cardiomyocytes. When Ambra1 expression was reduced by siRNA, the cardiomyocytes were more sensitive to staurosporine-induced apoptosis. In addition, co-immunoprecipitation of Ambra1 and Beclin1 demonstrated that Ambra1 and Beclin1 interact in serum-starved or rapamycin-treated cardiomyocytes, suggesting that Ambra1 regulates autophagy in cardiomyocytes by interacting with Beclin1. Finally, we determined that starvation stress-induced activation of Ambra1 contributes to the attenuation of adaptive AMP-activated protein kinase (AMPK) signaling. In conclusion, Ambra1 is a crucial regulator of autophagy and apoptosis through AMPK signaling pathway in cardiomyocytes that maintains the balance between autophagy and apoptosis. PMID- 25117442 TI - Dynamic regulation of the microtubule and actin cytoskeleton in zebrafish epiboly. AB - Gastrulation is a key developmental stage with striking changes in morphology. Coordinated cell movements occur to bring cells to their correct positions in a timely manner. Cell movements and morphological changes are accomplished by precisely controlling dynamic changes in cytoskeletal proteins, microtubules, and actin filaments. Among those cellular movements, epiboly produces the first distinct morphological changes in teleosts. In this review, I describe epiboly and its mechanics, and the dynamic changes in microtubule networks and actin structures, mainly in zebrafish embryos. The factors regulating those cytoskeletal changes will also be discussed. PMID- 25117443 TI - Inhibition of N-acetylglucosaminyltransferase V enhances sensitivity of radiotherapy in human prostate cancer. AB - The purpose of this study was to investigate the relationship between N acetylglucosaminyltransferase V (GnT-V) and radiation sensitivity of prostate cancer (PCa) cells both in vitro and in vivo. Firstly, the GnT-V expression was studied in 84 cases of PCa tissues, in which higher level of GnT-V was detected more frequently in the advanced tumors. Secondly, the GnT-V stably suppressed cell lines PCa/1079 (Lncap/1079 and PC3/1079) were constructed from PCa cell lines (Lncap and PC3) in vitro. Attenuation of GnT-V inhibited cell proliferation, migration and increased apoptosis, which resulted in enhanced radiation sensitivity of PCa cells. The underlying mechanism may be relevant to the increasing ratio of Bax/Bcl-2, the blocking transcription of NF-kappaB and the reduction of cell cycle G2-M arrest. Finally, in in vivo study, compared with control groups, the irradiated PCa xenograft nude mice of PCa/1079 indicated to reduce tumor-growth rate and enhance survival time. Summary, our studies showed that inhibition of GnT-V probably improved PCa cells' radiation sensitivity. PMID- 25117444 TI - Viral and chloroplastic signals essential for initiation and efficiency of translation in Agrobacterium tumefaciens. AB - The construction of high-level protein expression vectors using the CaMV 35S promoter in concert with highly efficient translation initiation signals for Agrobacterium tumefaciens is a relatively less explored field compared to that of Escherichia coli. In the current study, we experimentally investigated the capacity of the CaMV 35S promoter to direct GFP gene expression in A. tumefaciens in the context of different viral and chloroplastic translation initiation signals. GFP expression and concomitant translational efficiency was monitored by confocal microscopy and Western blot analysis. Among all of the constructs, the highest level of translation was observed for the construct containing the phage T7 translation initiation region followed by the chloroplastic Rubisco Large Subunit (rbcL) 58-nucleotide 5' leader region including its SD-like sequence (GGGAGGG). Replacing the SD-like (GGGAGGG) with non SD-like (TTTATTT) or replacing the remaining 52 nucleotides of rbcL with nonspecific sequence completely abolished translation. In addition, this 58 nucleotide region of rbcL serves as a translational enhancer in plants when located within the 5' UTR of mRNA corresponding to GFP. Other constructs, including those containing sequences upstream of the coat proteins of Alfalfa Mosaic Virus, or the GAGG sequence of T4 phage or the chloroplastic atpI and/or PsbA 5' UTR sequence, supported low levels of GFP expression or none at all. From these studies, we propose that we have created high expression vectors in A. tumefaciens and/or plants which contain the CaMV 35S promoter, followed by the translationally strong T7 SD plus RBS translation initiation region or the rbcL 58-nucleotide 5' leader region upstream of the gene of interest. PMID- 25117445 TI - Nitrosylation of c heme in cd(1)-nitrite reductase is enhanced during catalysis. AB - The reduction of nitrite into nitric oxide (NO) in denitrifying bacteria is catalyzed by nitrite reductase. In several species, this enzyme is a heme containing protein with one c heme and one d1 heme per monomer (cd1NiR), encoded by the nirS gene. For many years, the evidence of a link between NO and this hemeprotein represented a paradox, given that NO was known to tightly bind and, possibly, inhibit hemeproteins, including cd1NiRs. It is now established that, during catalysis, cd1NiRs diverge from "canonical" hemeproteins, since the product NO rapidly dissociates from the ferrous d1 heme, which, in turn, displays a peculiar "low" affinity for NO (KD=0.11 MUM at pH 7.0). It has been also previously shown that the c heme reacts with NO at acidic pH but c heme nitrosylation was not extensively investigated, given that in cd1NiR it was considered a side reaction, rather than a genuine process controlling catalysis. The spectroscopic study of the reaction of cd1NiR and its semi-apo derivative (containing the sole c heme) with NO reported here shows that c heme nitrosylation is enhanced during catalysis; this evidence has been discussed in order to assess the potential of c heme nitrosylation as a regulatory process, as observed for cytochrome c nitrosylation in mammalian mitochondria. PMID- 25117446 TI - Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells. AB - Arsenic trioxide (As2O3) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As2O3 induced apoptosis of human papillomavirus (HPV) 16 DNA immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As2O3 on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV negative C33A cells were more sensitive to growth inhibition induced by As2O3 than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As2O3 than HPV 16-positive CaSki and SiHa cells. After As2O3 treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As2O3 is a potential anticancer drug for cervical cancer. PMID- 25117448 TI - Analyses on the mechanisms that underlie the chondroprotective properties of calcitonin. AB - INTRODUCTION: Calcitonin (CT) has recently been shown to display chondroprotective effects. Here, we investigate the putative mechanisms by which CT delivers these actions. METHODS: Immortalized C-28/I2 cells or primary adult human articular chondrocytes (AHAC) were cultured in high-density micromasses to investigate: (i) CT anabolic effects using qPCR and immuhistochemistry analysis; (ii) CT anti-apoptotic effects using quantitation of Bax/Bcl gene products ratio, TUNEL assay and caspase-3 expression; (iii) CT effects on CREB, COL2A1 and NFAT transcription factors. RESULTS: CT (10(-10)-10(-8)nM) induced significant up regulation of cartilage phenotypic markers (SOX9, COL2A1 and ACAN), with down regulation of catabolic (MMP1 and MMP13 and ADAMTS5) gene products both in resting and inflammatory conditions. This was mirrored by an augmented production of type II collagen and accumulation of glycosaminoglycan- and proteoglycan-rich extracellular matrix in vitro. Mechanistic analyses revealed only partial involvement of cyclic AMP formation in these effects of CT. Congruently, using reporter assays for specific transcription factors, there was no indication for CREB activation, whereas the COL2A1 promoter was genuinely and directly activated by cell exposure to CT. Phenotypically, these mechanisms supported the ability of CT, whilst inactive on its own, to counteract the pro-apoptotic effects of IL 1beta, demonstrated by TUNEL-positive staining of chondrocytes and ratio of BAX/BCL genes products. CONCLUSION: These data may provide a novel lead for the development of CT-based chondroprotective strategies that rely on the engagement of mechanisms that lead to augmented chondrocyte anabolism and inhibited chondrocyte apoptosis. PMID- 25117447 TI - Laboratory test surveillance following acute kidney injury. AB - BACKGROUND: Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. METHODS: We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) >= 60 L/min/1.73 m(2). Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients. RESULTS: A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. CONCLUSIONS: Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease. PMID- 25117449 TI - The prognostic value of serum pregnancy-associated plasma protein A, S100 and high sensitivity C-reactive protein in acute ischemic stroke patients without heparin administration. AB - OBJECTIVES: The concerns regarding the pre-analytical bias caused by medicine treatments have been raised in the diagnosis and prognosis of ischemic stroke recently. The aim of this study was to examine the prognostic value of serum pregnancy-associated plasma protein A (PAPP-A), S100 and high sensitivity C reactive protein (hs-CRP) in heparin-naive patients of acute ischemic stroke. DESIGN AND METHODS: Serum levels of PAPP-A, S100 and hs-CRP were determined in 205 heparin-naive patients of acute ischemic stroke and 50 healthy controls. Clinical information and radiological information were collected. Unfavorable outcomes (stroke recurrence, myocardial infarction or death) were also recorded after six months. The associations between serum biomarker levels and stroke severity/outcome were assessed. RESULTS: Serum PAPP-A, S100 and hs-CRP levels increased in patients compared with controls (P<0.05). S100 and hs-CRP levels were significantly higher in patients with larger cerebral infarction sizes (P<0.05) and more severe neurological impairment (P<0.05). Serum PAPP-A level showed a progressive increase with the increase of stroke severity (P<0.05). Serum hs-CRP and National Institutes of Health Stroke Scale (NIHSS) scores were identified as independent predictors for unfavorable outcomes with odds ratios of 2.884 (1.154 to 7.210, P=0.023) and 2.887 (1.146 to 7.273, P=0.024), respectively. CONCLUSION: Serum PAPP-A, S100 and hs-CRP were associated with stroke severity or outcome after ischemic stroke and may offer complementary information, essential for clinical decision making. Serum PAPP-A showed a potential value for the evaluation of stroke clinically. PMID- 25117451 TI - Amniotic membrane modulates innate immune response inhibiting PRRs expression and NF-kappaB nuclear translocation on limbal myofibroblasts. AB - Corneal damage observed in a viral infection such as herpetic stromal keratitis is mainly caused by proinflammatory molecules released by resident cells in the response to viral antigens. There are pattern recognition receptors like MDA5, RIG-1, and TLR3, that recognize viral dsRNA and after activation, the innate immune response is exacerbated inducing the synthesis and secretion of inflammatory cytokines through NF-kappaB activation. Amniotic membrane (AM) has demonstrated to reduce inflammation by several mechanisms, however the effect of AM on innate immune receptors such as MDA5, RIG-1, and TLR3 has not been reported. In this study, we have determined that the presence of AM significantly inhibited the synthesis and secretion of proinflammatory cytokines on human limbal myofibroblasts (HLM) stimulated with poly I:C. Similarly, the presence of AM reduced the protein expression of MDA5, RIG-1, and TLR3 on poly I:C stimulated HLM. Additionally, the presence of the AM significantly inhibited the NF-kappaB nuclear translocation when the HLM were poly I:C stimulated, and concomitantly, the AM was able to relocate cadherins affecting the myofibroblastic cellular morphology. These results suggest that AM generates an anti-inflammatory microenvironment, and specific inhibition of NFkappaB nuclear translocation on infected corneal tissue would reduce the inflammation undesirable effects, explaining in part the beneficial usefulness of transplanting AM on herpetic stromal keratitis. PMID- 25117450 TI - Autism-specific covariation in perceptual performances: "g" or "p" factor? AB - BACKGROUND: Autistic perception is characterized by atypical and sometimes exceptional performance in several low- (e.g., discrimination) and mid-level (e.g., pattern matching) tasks in both visual and auditory domains. A factor that specifically affects perceptive abilities in autistic individuals should manifest as an autism-specific association between perceptual tasks. The first purpose of this study was to explore how perceptual performances are associated within or across processing levels and/or modalities. The second purpose was to determine if general intelligence, the major factor that accounts for covariation in task performances in non-autistic individuals, equally controls perceptual abilities in autistic individuals. METHODS: We asked 46 autistic individuals and 46 typically developing controls to perform four tasks measuring low- or mid-level visual or auditory processing. Intelligence was measured with the Wechsler's Intelligence Scale (FSIQ) and Raven Progressive Matrices (RPM). We conducted linear regression models to compare task performances between groups and patterns of covariation between tasks. The addition of either Wechsler's FSIQ or RPM in the regression models controlled for the effects of intelligence. RESULTS: In typically developing individuals, most perceptual tasks were associated with intelligence measured either by RPM or Wechsler FSIQ. The residual covariation between unimodal tasks, i.e. covariation not explained by intelligence, could be explained by a modality-specific factor. In the autistic group, residual covariation revealed the presence of a plurimodal factor specific to autism. CONCLUSIONS: Autistic individuals show exceptional performance in some perceptual tasks. Here, we demonstrate the existence of specific, plurimodal covariation that does not dependent on general intelligence (or "g" factor). Instead, this residual covariation is accounted for by a common perceptual process (or "p" factor), which may drive perceptual abilities differently in autistic and non autistic individuals. PMID- 25117455 TI - Simultaneous visualization of graphene grain boundaries and wrinkles with structural information by gold deposition. AB - Although line defects such as grain boundaries (GBs) and wrinkles are unavoidable in graphene, difficulties in identification preclude studying their impact on electronic and mechanical properties. As previous methods focus on a single type of line defect, simultaneous measurements of both GBs and wrinkles with detailed structural information have not been reported. Here, we introduce effective visualization of both line defects by controlled gold deposition. Upon depositing gold on graphene, single lines and double lines of gold nanoparticles (NPs) are formed along GBs and wrinkles, respectively. Moreover, it is possible to analyze whether a GB is stitched or overlapped, whether a wrinkle is standing or folded, and the width of the standing collapsed wrinkle. Theoretical calculations show that the characteristic morphology of gold NPs is due to distinct binding energies of line defects, which are correlated to disrupting diffusion of NPs. Our approach could be further exploited to investigate the defect structures of other two-dimensional materials. PMID- 25117452 TI - Chinese bone turnover marker study: reference ranges for C-terminal telopeptide of type I collagen and procollagen I N-terminal peptide by age and gender. AB - BACKGROUND: Bone formation marker procollagen I N-terminal peptide (PINP) and resorption marker C-terminal telopeptide of type I collagen (beta-CTX) are useful biomarkers for differential diagnosis and therapeutic evaluation of osteoporosis, but reference values are required. METHODS: The multi-center, cross-sectional Chinese Bone Turnover Marker Study included 3800 healthy volunteers in 5 Chinese cities. Serum PINP, beta-CTX, parathyroid hormone (PTH) and 25OHD levels were measured by chemiluminescence assay. Lumbar spine and proximal femur BMD were measured by dual-energy X-ray absorptiometry. Serum PINP and beta-CTX levels were assessed by age, gender, weight, recruitment latitude, levels of PTH and 25OHD. RESULTS: Subjects (n = 1436, M:F, 500:936; mean age 50.6 +/- 19.6 years) exhibited non-normally distributed PINP and beta-CTX peaking between 15-19 years, gradually declining throughout adulthood, elevating within 10 years of postmenopause, and then declining by age 70. In women between the age of 30 and menopause, median PINP and beta-CTX levels were 40.42 (95% CI: 17.10-102.15) and 0.26 (95% CI: 0.08-0.72) ng/mL, respectively. beta-CTX and PINP were positively linearly correlated (r = 0.599, P<0.001). beta-CTX correlated positively (r = 0.054 and 0.093) and PINP correlated negatively (r = -0.012 and -0.053) with 25OHD and PTH (P<0.05). CONCLUSIONS: We established Chinese reference ranges for PINP and CTX. Chinese individuals exhibited high serum PINP and beta-CTX levels between 15 and 19 years of age and at menopause, which gradually declined after 70 years of age. PMID- 25117453 TI - Zinc finger MYND-type containing 8 promotes tumour angiogenesis via induction of vascular endothelial growth factor-A expression. AB - Zinc finger, MYND-type containing 8 (ZMYND8) encodes a receptor for activated C kinase protein. Here, we report that ZMYND8 promotes angiogenesis in prostate cancer xenografts in zebrafish, as well as tube formation in human umbilical vascular endothelial cell (HUVEC) cultures. Using transcriptome analyses, we found upregulation of ZMYND8 expression in both zebrafish prostate cancer xenografts and prostate cancer samples from patients. In vitro and in vivo ZMYND8 knockdown suppressed angiogenesis, whereas ZMYND8 overexpression enhanced angiogenesis. Notably, ZMYND8 induced vegfa mRNA expression selectively in prostate cancer xenografts. Integrated analysis of human and zebrafish transcriptomes, which identified ZMYND8, might be a powerful strategy to determine also other molecular targets for inhibiting prostate cancer progression. PMID- 25117454 TI - Selenoprotein K form an intermolecular diselenide bond with unusually high redox potential. AB - Selenoprotein K (SelK) is a membrane protein involved in antioxidant defense, calcium regulation and the ER-associated protein degradation pathway. We found that SelK exhibits a peroxidase activity with a rate that is low but within the range of other peroxidases. Notably, SelK reduced hydrophobic substrates, such as phospholipid hydroperoxides, which damage membranes. Thus, SelK might be involved in membrane repair or related pathways. SelK was also found to contain a diselenide bond-the first intramolecular bond of that kind reported for a selenoprotein. The redox potential of SelK was -257 mV, significantly higher than that of diselenide bonds in small molecules or proteins. Consequently, SelK can be reduced by thioredoxin reductase. These finding are essential for understanding SelK activity and function. PMID- 25117458 TI - Photocurrent spectroscopy of (n, m) sorted solution-processed single-walled carbon nanotubes. AB - Variable-wavelength photocurrent microscopy and photocurrent spectroscopy are used to study the photoresponse of (n, m) sorted single-walled carbon nanotube (SWNT) devices. The measurements of (n, m) pure SWCNT devices demonstrate the ability to study the wavelength-dependent photoresponse in situ in a device configuration and deliver photocurrent spectra that reflect the population of the source material. Furthermore, we show that it is possible to map and determine the chirality population within a working optoelectronic SWCNT device. PMID- 25117457 TI - Chronic total occlusions in Sweden--a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). AB - INTRODUCTION: Evidence for the current guidelines for the treatment of patients with chronic total occlusions (CTO) in coronary arteries is limited. In this study we identified all CTO patients registered in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and studied the prevalence, patient characteristics and treatment decisions for CTO in Sweden. METHODS AND RESULTS: Between January 2005 and January 2012, 276,931 procedures (coronary angiography or percutaneous coronary intervention) were performed in 215,836 patients registered in SCAAR. We identified all patients who had 100% luminal diameter stenosis known or assumed to be >= 3 months old. After exclusion of patients with previous coronary artery bypass graft (CABG) surgery or coronary occlusions due to acute coronary syndrome, we identified 16,818 CTO patients. A CTO was present in 10.9% of all coronary angiographies and in 16.0% of patients with coronary artery disease. The majority of CTO patients were treated conservatively and PCI of CTO accounted for only 5.8% of all PCI procedures. CTO patients with diabetes and multivessel disease were more likely to be referred to CABG. CONCLUSION: CTO is a common finding in Swedish patients undergoing coronary angiography but the number of CTO procedures in Sweden is low. Patients with CTO are a high-risk subgroup of patients with coronary artery disease. SCAAR has the largest register of CTO patients and therefore may be valuable for studies of clinical importance of CTO and optimal treatment for CTO patients. PMID- 25117456 TI - The effects of intraperitoneal clenbuterol injection on protein degradation and myostatin expression differ between the sartorius and pectoral muscles of neonatal chicks. AB - The purpose of this study was to investigate the effects of injection of the beta2-adrenergic receptor agonist clenbuterol on the skeletal muscles of neonatal chicks (Gallus gallus domesticus). One-day-old chicks were randomly divided into four groups and given a single intraperitoneal injection of clenbuterol (0.01, 0.1, or 1mg/kg) or phosphate-buffered saline. Twenty-four hours after the injection, the sartorius muscles (which consist of both slow- and fast-twitch fibers) of chicks that received 0.01 or 0.1mg/kg clenbuterol were significantly heavier than those of controls, while there were no between-group differences in the weight of the pectoral muscles, which consist of only fast-twitch fibers. Muscle free N(t)-methylhistidine, regarded as an index of myofibrillar proteolysis, was decreased in the sartorius muscle of the clenbuterol-injected chicks, while it was not affected in the pectoral muscles. In the sartorius muscle of the clenbuterol-injected chicks, myostatin and atrogin-1/MAFbx mRNA expressions were decreased, while insulin-like growth factor-I was unaffected. These observations suggested, in 1-day-old chicks, clenbuterol might increase mass of the sartorius muscle by decreasing myostatin gene expression and protein degradation. PMID- 25117459 TI - The effects of lactation on impulsive behavior in vasopressin-deficient Brattleboro rats. AB - Vasopressin (AVP)-deficient Brattleboro rats develop a specific behavioral profile, which-among other things-include altered cognitive performance. This profile is markedly affected by alterations in neuroendocrine state of the animal such as during lactation. Given the links between AVP and cognition we hypothesized that AVP deficiency may lead to changes in impulsivity that is under cognitive control and the changes might be altered by lactation. Comparing virgin and lactating AVP-deficient female Brattleboro rats to their respective controls, we assessed the putative lactation-dependent effects of AVP deficiency on impulsivity in the delay discounting paradigm. Furthermore, to investigate the basis of such effects, we assessed possible interactions of AVP deficiency with GABAergic and serotonergic signaling and stress axis activity, systems playing important roles in impulse control. Our results showed that impulsivity was unaltered by AVP deficiency in virgin rats. In contrast a lactation-induced increase in impulsivity was abolished by AVP deficiency in lactating females. We also found that chlordiazepoxide-induced facilitation of GABAergic and imipramine induced enhancement of serotonergic activity in virgins led to increased and decreased impulsivity, respectively. In contrast, during lactation these effects were visible only in AVP-deficient rats. These rats also exhibited increased stress axis activity compared to virgin animals, an effect that was abolished by AVP deficiency. Taken together, AVP appears to play a role in the regulation of impulsivity exclusively during lactation: it has an impulsivity increasing effect which is potentially mediated via stress axis-dependent mechanisms and fine tuning of GABAergic and serotonergic function. PMID- 25117460 TI - Clinical characteristics of pain in patients with pituitary adenomas. AB - OBJECTIVE: Clinical presentation of pituitary adenomas frequently involves pain, particularly headache, due to structural and functional properties of the tumour. Our aim was to investigate the clinical characteristics of pain in a large cohort of patients with pituitary disease. DESIGN: In a cross-sectional study, we assessed 278 patients with pituitary disease (n=81 acromegaly; n=45 Cushing's disease; n=92 prolactinoma; n=60 non-functioning pituitary adenoma). METHODS: Pain was studied using validated questionnaires to screen for nociceptive vs neuropathic pain components (painDETECT), determine pain severity, quality, duration and location (German pain questionnaire) and to assess the impact of pain on disability (migraine disability assessment, MIDAS) and quality of life (QoL). RESULTS: We recorded a high prevalence of bodily pain (n=180, 65%) and headache (n=178, 64%); adrenocorticotropic adenomas were most frequently associated with pain (n=34, 76%). Headache was equally frequent in patients with macro- and microadenomas (68 vs 60%; P=0.266). According to painDETECT, the majority of the patients had a nociceptive pain component (n=193, 80%). Despite high prevalence of headache, 72% reported little or no headache-related disability (MIDAS). Modifiable factors including tumour size, genetic predisposition, previous surgery, irradiation or medical therapy did not have significant impact neither on neuropathic pain components (painDETECT) nor on headache-related disability (MIDAS). Neuropathic pain and pain-related disability correlated significantly with depression and impaired QoL. CONCLUSIONS: Pain appears to be a frequent problem in pituitary disease. The data suggest that pain should be integrated in the diagnostic and therapeutic work-up of patients with pituitary disease in order to treat them appropriately and improve their QoL. PMID- 25117462 TI - Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected patients receiving current antiretroviral drugs. AB - OBJECTIVE: HIV-infected patients had a higher prevalence of insulin resistance (IR) and risk of diabetes mellitus (DM) than that observed in healthy controls, but there are no data about the current prevalence considering the changes in HIV presentation and the use of newer antiretroviral drugs. DESIGN: Longitudinal study which involved 265 HIV patients without DM, receiving first (n=71) and advanced lines of antiretroviral therapy (n=194). METHODS: Prevalence of IR according to clinical and anthropometric variables, including dual X-ray absorptiometry (DXA) scan evaluation. IR was defined as homeostasis model assessment of IR>=3.8. Incident DM was assessed during the follow-up. RESULTS: First-line patients had a short time of HIV infection, less hepatitis C virus coinfection, and received mainly an efavirenz-based regimen. Overall, the prevalence of IR was 21% (55 patients, 6% in first-line, 27% in pretreated). In a logistic regression analysis, significant associations were found between the waist/hip circumference ratio (RR 10; 95% CI 1.66-16; P<0.01, per unit), and central fat in percentage (RR 1.08; 95% CI 1.01-1.17; P=0.04, per unit) as evaluated by DXA, and IR. During 770.8 patient-years, DM was diagnosed in 8% (22 patients), mostly in pretreated patients (10 vs 4%; P=0.1). Thus, the overall rate of incident DM was 2.85 per 100 person-years, mostly in previous IR (10.39 vs 0.82/100 person-years; P=0.01). CONCLUSIONS: A lower prevalence of IR is observed in the current HIV-infected patients with fewer risk factors and receiving newer antiretroviral drugs. IR continues to identify patients at high risk for developing DM in the short term. PMID- 25117461 TI - Alcohol and the risk for latent autoimmune diabetes in adults: results based on Swedish ESTRID study. AB - OBJECTIVE: Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with the risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. DESIGN: A population-based case control study was carried out to investigate the association of alcohol consumption and the risk of LADA. METHODS: We used data from the ESTRID case control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies (GADAs) positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged >=35. Logistic regression was used to estimate the odds ratios (ORs) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. RESULTS: Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% CI 0.92-0.99 for every 5-g increment in daily intake). Similar results were observed for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA levels (OR 0.85, 95% CI 0.76-0.94/5 g alcohol per day), whereas no association was observed with LADA having high GADA levels (OR 1.00, 95% CI 0.94-1.06/5 g per day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (P=0.0312), and a 10% reduction in homeostasis model assessment of insulin resistance (P=0.0418). CONCLUSIONS: Our findings indicate that alcohol intake may reduce the risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity. PMID- 25117463 TI - Hypogonadism as an additional indication for bariatric surgery in male morbid obesity? AB - OBJECTIVE: Male obesity is often associated with reduced levels of circulating total (TT) and calculated free testosterone (cFT), with normal/reduced gonadotropins. Bariatric surgery often improves sex steroid and sex hormone binding globulin (SHBG) levels. The aim of this study was to assess the effects of bariatric surgery on waist circumference (WC) and BMI, and on TT levels, in morbidly obese men, stratified, according to the gonadal state, in eugonadal and hypogonadal (TT<8 nmol/l) subjects. DESIGN: A cohort of morbidly obese patients (29 with hypogonadism (HG) and 26 without) undergoing bariatric surgery (37, 10, 6, and 2, with Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, biliopancreatic diversion and gastric sleeve, respectively) was studied at 6 and 12 months from the operation. METHODS: Anthropometric parameters (weight, BMI, WC) and sex hormones (gonadotropins, TT, cFT, estradiol (E2), SHBG) were assessed. RESULTS: WC was the only parameter significantly correlated with androgens, but not with E2, SHBG, and gonadotropins, at baseline. After surgery, a significant increase in TT, cFT, and SHBG, accompanied by a decrease in E2, was evident in the two groups. However, both TT and cFT, but not E2, SHBG, and gonadotropin variations, were significantly higher in the hypogonadal group at follow-up, with an overall 93% complete recovery from HG. Reduction in WC, but not BMI, was significantly greater in hypogonadal men (DeltaWC=-29.4+/-21.6 vs 14.4+/-17.4 at 12 months, P=0.047). CONCLUSIONS: Recovery from obesity-associated HG is one of the beneficial effects of bariatric surgery in morbidly obese men. The present findings suggest that the gonadal state is a predictor of WC decrease after bariatric surgery. PMID- 25117464 TI - Cardiovascular risk in women with type 2 diabetes mellitus and prediabetes: is it indeed higher than men? AB - The relative risk for cardiovascular disease (CVD) events and mortality in diabetic women (in comparison with non-diabetic women) is believed to be greater than that in diabetic men. However, the absolute risk for CVD mortality and morbidity does not appear to be higher in women. In general, there is heterogeneity between studies, and whether there is any definite difference in the CVD risk between sexes at any level of glycaemia is not known. The same arguments also apply when comparing the CVD risk factors, such as lipid profiles and systemic inflammation indices, which seem to be worse in women than in men with diabetes mellitus (DM). The same questions emerge at any given glycaemic state: are women at worse risk and do they have a worse risk factor profile than men? These issues have yet to be resolved. Similar, though less extensive, data have been reported for prediabetes. Furthermore, women with DM are suboptimally treated compared with men regarding lipid and blood pressure targets. Large prospective studies representative of the general population are therefore needed to define the differences between sexes regarding CVD events and mortality at a given glucose level and after adjusting for any other confounders. PMID- 25117465 TI - GEPNETs update: Radionuclide therapy in neuroendocrine tumors. AB - Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors (GEPNETs) patients. Most studies report objective response rates in 15-35% of patients. Also, outcome in terms of progression free survival (PFS) and overall survival compares very favorably with that for somatostatin analogs, chemotherapy, or new, 'targeted' therapies. They also compare favorably to PFS data for liver-directed therapies. Two decades after the introduction of PRRT, there is a growing need for randomized controlled trials comparing PRRT to 'standard' treatment, that is treatment with agents that have proven benefit when tested in randomized trials. Combining PRRT with liver-directed therapies or with targeted therapies could improve treatment results. The question to be answered, however, is whether a combination of therapies performed within a limited time span from one another results in a better PFS than a strategy in which other therapies are reserved until after (renewed) tumor progression. Randomized clinical trials comparing PRRT with other treatment modalities should be undertaken to determine the best treatment options and treatment sequelae for patients with GEPNETs. PMID- 25117466 TI - Ten weeks of aerobic training does not result in persistent changes in VLDL triglyceride turnover or oxidation in healthy men. AB - OBJECTIVE: Very low density lipoprotein triglyceride (VLDL-TG) and free fatty acids (FFA) constitute a substantial proportion of human energy supply both at rest and during exercise. Exercise acutely decreases VLDL-TG concentration, and VLDL-TG clearance is increased after an exercise bout. However, the effects of long-term training are not clear. DESIGN: The aim was to investigate long-term effects of training by direct assessments of VLDL-TG and palmitate kinetics and oxidation in healthy lean men (n=9) at rest, before and after a 10-week training program, compared with a non-training control group (n=9). METHODS: VLDL-TG kinetics were assessed by a primed constant infusion of [1-14C]VLDL-TG, and VLDL TG oxidation by specific activity (14CO2) in expired air. The metabolic study days were placed 60-72 h after the last exercise bout. RESULTS: Palmitate kinetics and oxidation were assessed by a 2 h constant infusion of [9,10 (3)H]palmitate. In the training group (n=9), maximal oxygen uptake increased significantly by ~20% (P<0.05), and the insulin sensitivity (assessed by the hyperinsulinemic-euglycemic clamp) improved significantly (P<0.05). Despite these metabolic improvements, no changes were observed in VLDL-TG secretion, clearance, or oxidation or in palmitate kinetics. CONCLUSION: We conclude that 10 weeks of exercise training did not induce changes in VLDL-TG and palmitate kinetics in healthy lean men. PMID- 25117467 TI - Nanocrystalline calcitic lens arrays fabricated by self-assembly followed by amorphous-to-crystalline phase transformation. AB - Natural calcium carbonate-based nanocomposites often have superior physical properties and provide a comprehensive source for bioinspired synthetic materials. Here we present thermodynamically stable, transparent CaCO3 microlens arrays (MLA) produced by transforming an amorphous CaCO3 phase into nanocrystalline calcite. We analyze the structure and properties of crystallized MLA by X-ray scattering, transmitted and polarized light microscopy, and electron microscopy and find that MLA are crystallized in spherulite-like patterns without changing the shape of the microlens. The key finding is that nanocrystallinity of the calcite formed diminishes structural anisotropy on the wavelength scale and results in greatly reduced birefringent effects. The remnant preferred orientation of the optical axes of calcite crystals in the plane of the microlens arrays leads to some directionality of optical properties, which may be beneficial for technical applications. PMID- 25117468 TI - Cardiac fibrosis in end-stage human heart failure and the cardiac natriuretic peptide guanylyl cyclase system: regulation and therapeutic implications. AB - Left ventricular assist device (LVAD) support has been used in the treatment of end-stage heart failure (HF), however use of anti-fibrotic co-therapies may improve prognosis. Natriuretic peptides (NPs) possess anti-fibrotic properties through their receptors, GC-A/GC-B/NPR-C. We sought to evaluate cardiac fibrosis and the endogenous NP system in end-stage HF with and without LVAD therapy and to assess the anti-fibrotic actions of the dual GC-A/-B activator CD-NP in vitro. Collagen (Col) protein content was assessed by Picrosirius Red staining and NPs, NP receptors, and Col I mRNA expression were determined by qPCR in LV tissue from patients in end-stage HF (n=13), after LVAD support (n=5) and in normal subjects (n=6). Col I mRNA and protein levels in cardiac fibroblasts (CFs) pretreated with CD-NP were compared to those of BNP or CNP pretreatment. The LV in end-stage HF was characterized by higher Col I mRNA expression and Col protein deposition compared to normal which was sustained after LVAD support. ANP and BNP mRNA expressions were higher while CNP was lower in end-stage HF LV. GC-A expression did not change while GC-B and NPR-C increased compared to normal LV. The changes in NP system expression were not reversed after LVAD support. In vitro, CD-NP reduced Col I production stimulated by TGF-beta 1 greater than BNP or CNP in CFs. We conclude that the failing LV is characterized by increased fibrosis and reduced CNP gene expression. LVAD support did not reverse Col deposition nor restore CNP production, suggesting a therapeutic opportunity for CD-NP. PMID- 25117471 TI - Mercury telluride colloidal quantum dots: electronic structure, size-dependent spectra, and photocurrent detection up to 12 MUm. AB - HgTe colloidal quantum dots are synthesized with high monodispersivity with sizes up to ~15 nm corresponding to a room temperature absorption edge at ~5 MUm. The shape is tetrahedral for larger sizes and up to five peaks are seen in the absorption spectra with a clear size dependence. The size range of the HgTe quantum dots is extended to ~20 nm using regrowth. The corresponding room temperature photoluminescence and absorption edge reach into the long-wave infrared, past 8 MUm. Upon cooling to liquid nitrogen temperature, a photoconductive response is obtained in the long-wave infrared region up to 12 MUm. Configuration-interaction tight-binding calculations successfully explain the spectra and the size dependence. The five optical features can be assigned to sets of single hole to single electron transitions whose strengths are strongly influenced by the multiband/multiorbital character of the quantum-dot electronic states. PMID- 25117469 TI - TSLPR deficiency attenuates atherosclerotic lesion development associated with the inhibition of TH17 cells and the promotion of regulator T cells in ApoE deficient mice. AB - AIMS: We generated thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice to directly explore the role of thymic stromal lymphopoietin (TSLP) in atherogenesis. METHODS AND RESULTS: Both thymic stromal lymphopoietin (TSLP) and its receptor are expressed in atherosclerotic aortas of apolipoprotein E knockout (ApoE KO) mice. Serum thymic stromal lymphopoietin (TSLP) is markedly increased in apolipoprotein E knockout (ApoE KO) mice fed with a high fat diet (HFD). Arterial lesion formation was significantly decreased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E double knockout (ApoE-TSLPR DKO) mice compared with apolipoprotein E knockout (ApoE KO) mice. Bone marrow chimera studies indicated reduced lesions in apolipoprotein E knockout (ApoE KO) mice which received the bone marrow of thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE TSLPR DKO) mice as well as in TSLPR KO mice which received bone marrow of ApoE TSLPR DKO mice. Compared with apolipoprotein E knockout (ApoE KO) mice, IFN-gamma secretion by activated T cells was increased but IL-4 expression was reduced in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice. Consisted with these results, the mRNA of IFN-gamma was increased but IL-4 was reduced in root. These findings suggest that a reduction in atherosclerotic lesions in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice may not be due to a Th1/Th2 imbalance. On the other hand, the number of Th17 cells, the secretion of IL-17A by activated CD4(+) T cells and the mRNA expression of IL-17A in root were decreased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E double knockout (ApoE-TSLPR DKO) mice. Notably, the number of regulatory T cell expression of IL-10 was increased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice. CONCLUSIONS: Collectively, our data suggest that activating thymic stromal lymphopoietin (TSLP) promotes atherosclerosis by inducing Th17/Treg imbalance through thymic stromal lymphopoietin/thymic stromal lymphopoietin R-receptor (TSLP/TSLPR) signal way in apolipoprotein E-deficient mice fed with HFD model. PMID- 25117472 TI - A further note on the rises in sex ratio at birth during and just after the two World Wars. AB - It is well established that in most belligerent countries in World Wars 1 and 2, sex ratios (proportions male at birth) rose during and just after hostilities: then, a year or so later, they declined to normal levels. There is no established explanation for these phenomena. I have previously written on this problem. Here, I elaborate on my previous papers in three ways. First, further evidence (some analytic and some synthetic) is adduced to support the hypothesis that the rises were caused by high parental coital rates. Second, further evidence is adduced to suggest that these high coital rates occurred disproportionately often in couples of whom the man was (or had been) in the armed services. Thirdly, evidence is offered to suggest why such rises in sex ratio were not reported in other conflicts. PMID- 25117470 TI - Proteomic analysis reveals a novel function of the kinase Sat4p in Saccharomyces cerevisiae mitochondria. AB - The Saccharomyces cerevisiae kinase Sat4p has been originally identified as a protein involved in salt tolerance and stabilization of plasma membrane transporters, implicating a cytoplasmic localization. Our study revealed an additional mitochondrial (mt) localization, suggesting a dual function for Sat4p. While no mt related phenotype was observed in the absence of Sat4p, its overexpression resulted in significant changes of a specific mitochondrial subproteome. As shown by a comparative two dimensional difference gel electrophoresis (2D-DIGE) approach combined with mass spectrometry, particularly two groups of proteins were affected: the iron-sulfur containing aconitase-type proteins (Aco1p, Lys4p) and the lipoamide-containing subproteome (Lat1p, Kgd2p and Gcv3p). The lipoylation sites of all three proteins could be assigned by nanoLC-MS/MS to Lys75 (Lat1p), Lys114 (Kgd2p) and Lys102 (Gcv3p), respectively. Sat4p overexpression resulted in accumulation of the delipoylated protein variants and in reduced levels of aconitase-type proteins, accompanied by a decrease in the activities of the respective enzyme complexes. We propose a regulatory role of Sat4p in the late steps of the maturation of a specific subset of mitochondrial iron-sulfur cluster proteins, including Aco1p and lipoate synthase Lip5p. Impairment of the latter enzyme may account for the observed lipoylation defects. PMID- 25117474 TI - Accurate phylogenetic tree reconstruction from quartets: a heuristic approach. AB - Supertree methods construct trees on a set of taxa (species) combining many smaller trees on the overlapping subsets of the entire set of taxa. A 'quartet' is an unrooted tree over 4 taxa, hence the quartet-based supertree methods combine many 4-taxon unrooted trees into a single and coherent tree over the complete set of taxa. Quartet-based phylogeny reconstruction methods have been receiving considerable attentions in the recent years. An accurate and efficient quartet-based method might be competitive with the current best phylogenetic tree reconstruction methods (such as maximum likelihood or Bayesian MCMC analyses), without being as computationally intensive. In this paper, we present a novel and highly accurate quartet-based phylogenetic tree reconstruction method. We performed an extensive experimental study to evaluate the accuracy and scalability of our approach on both simulated and biological datasets. PMID- 25117473 TI - The microvascular effects of insulin resistance and diabetes on cardiac structure, function, and perfusion: a cardiovascular magnetic resonance study. AB - AIMS: Type 2 diabetes mellitus is an independent risk factor for the development of heart failure. To better understand the mechanism by which this occurs, we investigated cardiac structure, function, and perfusion in patients with and without diabetes. METHODS AND RESULTS: Sixty-five patients with no stenosis >30% on invasive coronary angiography were categorized into diabetes (19) and non diabetes (46) which was further categorized into prediabetes (30) and controls (16) according to the American Diabetes Association guidelines. Each patient underwent comprehensive cardiovascular magnetic resonance assessment. Left ventricular (LV) mass, relative wall mass (RWM), Lagrangian circumferential strain, LV torsion, and myocardial perfusion reserve (MPR) were calculated. LV mass was higher in diabetics than non-diabetics (112.8 +/- 39.7 vs. 91.5 +/- 21.3 g, P = 0.01) and in diabetics than prediabetics (112.8 +/- 39.7 vs. 90.3 +/- 18.7 g, P = 0.02). LV torsion angle was higher in diabetics than non-diabetics (9.65 +/- 1.90 vs. 8.59 +/- 1.91 degrees , P = 0.047), and MPR was lower in diabetics than non-diabetics (2.10 +/- 0.76 vs. 2.84 +/- 1.25 mL/g/min, P = 0.01). There was significant correlation between MPR and early diastolic strain rate (r = 0.310, P = 0.01) and LV torsion (r = -0.306, P = 0.01). In multivariable linear regression analysis, non-diabetics waist-hip ratio, but not body mass index, had a significant association with RWM (Beta = 0.34, P = 0.02). CONCLUSION: Patients with diabetes have increased LV mass, LV torsion, and decreased MPR. There is a significant association between decreased MPR and increased LV torsion suggesting a possible mechanistic link between microvascular disease and cardiac dysfunction in diabetes. PMID- 25117475 TI - Phase I dose-escalation study of cabazitaxel administered in combination with cisplatin in patients with advanced solid tumors. AB - INTRODUCTION: Cabazitaxel is a second-generation taxane with in vivo activity against taxane-sensitive and -resistant tumor cell lines and tumor xenografts. Cabazitaxel/cisplatin have therapeutic synergism in tumor-bearing mice, providing a rationale for assessing this combination in patients with solid tumors. METHODS: The primary objectives of this study were to determine dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of a cabazitaxel/cisplatin combined regimen (Part 1) and to assess antitumor activity at the MTD (Part 2). Safety and pharmacokinetics (PK) were also examined. RESULTS: Twenty-five patients with advanced solid tumors were enrolled (10 in Part 1; 15 in Part 2). In Part 1, two dose levels were evaluated; the MTD for cabazitaxel/cisplatin (given Q3W) was 15/75 mg/m(2). DLTs occurring during Cycle 1 at the maximum administered dose (20/75 mg/m(2); acute renal failure and febrile neutropenia) and the MTD (febrile neutropenia and hypersensitivity despite pre-medication) were as expected for taxane/platinum combinations. For the 18 patients treated at the MTD, the most frequent possibly related non-hematologic treatment-emergent adverse events (Grade >= 3) were nausea (16.7%), fatigue, acute renal failure and decreased appetite (each 11.1%). Neutropenia was the most frequent treatment emergent Grade >= 3 hematologic laboratory abnormality at the MTD (77.8%). The best overall response at the MTD was stable disease, observed in 66.7% of patients. PK results of the combination did not appear to differ from single agent administration for each agent. CONCLUSION: Combination treatment with cabazitaxel/cisplatin had a manageable safety profile; no PK interactions were evident. The recommended Phase II dose for this combination is cabazitaxel/cisplatin 15/75 mg/m(2) administered every 3 weeks. Antitumor activity findings suggest that further evaluation of this combination in disease specific trials is warranted. PMID- 25117476 TI - Identification of threshold prostate specific antigen levels to optimize the detection of clinically significant prostate cancer by magnetic resonance imaging/ultrasound fusion guided biopsy. AB - PURPOSE: Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. MATERIALS AND METHODS: We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. RESULTS: A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. CONCLUSIONS: Prostate cancer upgrading with targeted biopsy increases with an increasing prostate specific antigen cutoff. Above a prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically significant disease was achieved by targeted biopsy. In our population this corresponded to potentially sparing biopsy in 36% of patients who underwent multiparametric magnetic resonance imaging. Below this value 12-core biopsy detected more clinically insignificant cancer. Thus, the diagnostic usefulness of targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml or greater. PMID- 25117477 TI - High conopeptide diversity in Conus tribblei revealed through analysis of venom duct transcriptome using two high-throughput sequencing platforms. AB - The venom of each species of Conus contains different kinds of pharmacologically active peptides which are mostly unique to that species. Collectively, the ~500 700 species of Conus produce a large number of these peptides, perhaps exceeding 140,000 different types in total. To date, however, only a small fraction of this diversity has been characterized via transcriptome sequencing. In addition, the sampling of this chemical diversity has not been uniform across the different lineages in the genus. In this study, we used high-throughput transcriptome sequencing approach to further investigate the diversity of Conus venom peptides. We chose a species, Conus tribblei, as a representative of a poorly studied clade of Conus. Using the Roche 454 and Illumina platforms, we discovered 136 unique and novel putative conopeptides belonging to 30 known gene superfamilies and 6 new conopeptide groups, the greatest diversity so far observed from a transcriptome. Most of the identified peptides exhibited divergence from the known conopeptides, and some contained cysteine frameworks observed for the first time in cone snails. In addition, several enzymes involved in posttranslational modification of conopeptides and also some proteins involved in efficient delivery of the conopeptides to prey were identified as well. Interestingly, a number of conopeptides highly similar to the conopeptides identified in a phylogenetically distant species, the generalist feeder Conus californicus, were observed. The high diversity of conopeptides and the presence of conopeptides similar to those in C. californicus suggest that C. tribblei may have a broad range of prey preferences. PMID- 25117478 TI - Phylogenetic diversity and antibacterial activity of culturable fungi derived from the zoanthid Palythoa haddoni in the South China Sea. AB - Investigation on diversity of culturable fungi mainly focused on sponges and corals, yet little attention had been paid to the fungal communities associated with zoanthid corals. In this study, a total of 193 culturable fungal strains were isolated from the zoanthid Palythoa haddoni collected in the South China Sea, of which 49 independent isolates were identified using both morphological characteristics and internal transcribed spacer (ITS) sequence analyses. Thirty five strains were selected for phylogenetic analysis based on fungal ITS sequences. The results indicated that 18 genera within eight taxonomic orders of two phyla (seven orders of the phylum Ascomycota and one order of the phylum Basidiomycota) together with one unidentified fungal strain have been achieved, and Cladosporium sp. represented the dominant culturable genus. Particularly, 14 genera were isolated from a zoanthid for the first time. The antibacterial activities of organic extracts of mycelia and fermentation broth of 49 identified fungi were evaluated, and 29 (59.2 %) of the isolates displayed broad-spectrum or selective antibacterial activity. More interestingly, more than 60 % of the active fungal strains showed strong activity against two aquatic pathogenic bacteria Nocardia brasiliensis and Vibrio parahaemolyticus, compared with other pathogenic bacteria, indicating that zoanthid-derived fungi may protect its host against pathogens. This is the first report of systematically phylogenetic diversity and extensively antibacterial activity of zoanthid-derived fungi. PMID- 25117481 TI - Intraoperative and anesthesia-related cardiac arrest and its mortality in older patients: a 15-year survey in a tertiary teaching hospital. AB - BACKGROUND: Little information is known about factors that influence perioperative and anesthesia-related cardiac arrest (CA) in older patients. This study evaluated the incidence, causes and outcome of intraoperative and anesthesia-related CA in older patients in a Brazilian teaching hospital between 1996 and 2010. METHODS: During the study, older patients received 18,367 anesthetics. Data collected included patient characteristics, surgical procedures, American Society of Anesthesiologists (ASA) physical status, anesthesia type, medical specialty team and outcome. All CAs were categorized by cause into one of four groups: patient's disease/condition-related, surgery related, totally anesthesia-related or partially anesthesia-related. RESULTS: All intraoperative CAs and deaths rates are shown per 10,000 anesthetics. There were 100 CAs (54.44; 95% confidence intervals [CI]: 44.68-64.20) and 68 deaths (37.02; 95% CI: 27.56-46.48). The majority of CAs were patient's disease-/condition related (43.5; 95% CI: 13.44-73.68). There were six anesthesia-related CAs (3.26; 95% CI: 0.65-5.87) - 1 totally and 5 partially anesthesia-related, and three deaths, all partially anesthesia-related (1.63; 95% CI: 0.0-3.47). ASA I-II physical status patients presented no anesthesia-related CA. Anesthesia-related CA, absent in the last five years of the study, was due to medication-/airway related causes. ASA physical status was the most important predictor of CA (odds ratio: 14.52; 95% CI: 4.48-47.08; P<0.001) followed by emergency surgery (odds ratio: 8.07; 95% CI: 5.14-12.68; P<0.001). CONCLUSIONS: The study identified high incidence of intraoperative CAs with high mortality in older patients. The large majority of CAs were caused by factors not anesthesia-related. Anesthesia-related CA and mortality rates were 3.26 and 1.63 per 10,000 anesthetics, with no anesthesia-related CA in the last five years of the study. Major predictors of intraoperative CAs were poorer ASA physical status and emergency surgery. All anesthesia-related CAs were medication-related or airway-related, which is important for prevention strategies. PMID- 25117480 TI - Alteration of conserved alternative splicing in AMELX causes enamel defects. AB - Tooth enamel is the most highly mineralized tissue in vertebrates. Enamel crystal formation and elongation should be well controlled to achieve an exceptional hardness and a compact microstructure. Enamel matrix calcification occurs with several matrix proteins, such as amelogenin, enamelin, and ameloblastin. Among them, amelogenin is the most abundant enamel matrix protein, and multiple isoforms resulting from extensive but well-conserved alternative splicing and postsecretional processing have been identified. In this report, we recruited a family with a unique enamel defect and identified a silent mutation in exon 4 of the AMELX gene. We show that the mutation caused the inclusion of exon 4, which is almost always skipped, in the mRNA transcript. We further show, by generating and characterizing a transgenic animal model, that the alteration of the ratio and quantity of the developmentally conserved alternative splicing repertoire of AMELX caused defects in enamel matrix mineralization. PMID- 25117482 TI - A theoretical mathematical assessment of the effectiveness of coartemether in the treatment of Plasmodium falciparum malaria infection. AB - This study analysed the dynamics of blood stage malaria with immune response and under administration of Coartem as a combination therapy. The techniques of mathematical modelling were used in coming up and analysing the deterministic model. Sensitivity analysis and statistical approaches were used to compare model simulated treatment results with the use of Coartem and other antimalarial drugs. We sought to theoretically assess if Coartem can bring improvement in the treatment of malaria as compared to the other drugs. Our analysis and numerical results suggest that Coartem compares well with other antimalarial drug that have been on the market. However, the shortfall of our model is that it could not give good comparative results between Coartem treatment and other combination treatment schemes with similar mode of action. Our study predicted effects of different drug treatment protocols in malaria using a theoretical mathematical model, which gives an insight into potential effective treatment schemes. PMID- 25117484 TI - Prevention of surgical site infection: still an important challenge in colorectal surgery. PMID- 25117485 TI - Occurrence of estrogens in water, sediment and biota and their ecological risk in Northern Taihu Lake in China. AB - Occurrence of five estrogens, including estrone (E1), 17beta-estradiol (E2), estriol (E3), 17alpha-ethynylestradiol (EE2) and bisphenol A (BPA) in water, sediment and biota in Northern Taihu Lake, were investigated and their ecological risk was evaluated. Most of the target estrogens were widely distributed in the eight studied sampling sites, and their levels showed a regional trend of Gong Bay > Meiliang Bay > Zhushan Bay. The average concentrations of E1, E2, E3, EE2 and BPA ranged from 3.86 to 64.4 ng l(-1), 44.3 to 64.1 MUg kg(-1) dry weight and 58.6 to 115 MUg kg(-1) dry weight in water, sediments and biota, respectively. In most cases, the average concentrations of BPA and E2 were higher than those of other estrogens. E1, E3 and EE2 were found to be accumulated in river snails with bioaccumulation factor values as high as 14,204, 35,327 and 20,127 l kg(-1), respectively. E3 was also considered to be accumulated in clams. The evaluation of environmental risk showed that the occurrence of E2 and EE2 in lakes might pose a high risk to aquatic organisms. These findings provide important information for estrogen control and management in the studied area. PMID- 25117487 TI - Wavelet coherence analysis of prefrontal tissue oxyhaemoglobin signals as measured using near-infrared spectroscopy in elderly subjects with cerebral infarction. AB - This study aims to assess the prefrontal functional connectivity using wavelet coherence analysis of cerebral tissue oxyhaemoglobin concentration (Delta [HbO2]) signals in elderly subjects with cerebral infarction (CI) during the resting state. Continuous recordings of near-infrared spectroscopy (NIRS) signals were obtained from the left and right prefrontal lobes in 10 subjects with CI (age: 74.4+/-9.0years) and 18 healthy elderly subjects (age: 69.9+/-7.3years) during the resting state. The coherence between left and right prefrontal Delta [HbO2] oscillations in four frequency intervals (I, 0.6-2Hz; II, 0.145-0.6Hz; III, 0.052 0.145Hz and IV, 0.021-0.052Hz) was analyzed using wavelet coherence analysis. In healthy elderly subjects, the Delta [HbO2] oscillations were significantly wavelet coherent in intervals I and III (p<0.05), wavelet phase coherent in intervals from I to IV. In elderly subjects with CI, the left and right Delta [HbO2] oscillations were significantly wavelet coherent and phase coherent in interval I (p<0.05). In elderly subjects with CI, the power and phase coherences were significantly lower in interval III (p<0.01) than in healthy subjects. The difference in wavelet coherence between the healthy elderly and elderly with CI indicates an altered brain functional connectivity in CI patients. This may be useful for assessing the effectiveness of functional recovery following a CI. PMID- 25117486 TI - Residents health risk of Pb, Cd and Cu exposure to street dust based on different particle sizes around zinc smelting plant, Northeast of China. AB - The residents health risk of Pb, Cd and Cu exposure to street dust with different particle sizes (<100 and <63 MUm) near Huludao Zinc Plant (HZP) was investigated in this study. The average concentrations of Pb, Cd and Cu in the <100-MUm and <63-MUm dust were 1,559, 178.5, 917.9 and 2,099, 198.4, 1,038 mg kg(-1), respectively. It showed that smaller particles tended to contain higher element concentrations. Metals in dust around HZP decreased gradually from the zinc smelter to west and east directions. There was significantly positive correlation among Pb, Cd and Cu in street dust with different particle sizes. The contents of Pb, Cd and Cu in dust increased with decreasing pH or increasing organic matter. Non-carcinogenic health risk assessment showed that the health index (HI) for children and adult exposed to <63-MUm particles were higher than exposed to <100 MUm particles, which indicated that smaller particles tend to have higher non carcinogenic health risk. Non-carcinogenic risk of Pb was the highest in both particle sizes, followed by Cd and Cu. HI for Pb and Cd in both particle sizes for children had exceeded the acceptable value, indicated that children living around HZP were experiencing the non-carcinogenic health risk from Pb and Cd exposure to street dust. PMID- 25117488 TI - Podocyte proteins in congenital and minimal change nephrotic syndrome. AB - BACKGROUND: Podocyte foot process effacement is a uniform finding in kidneys with heavy proteinuria. Its molecular mechanisms, however, are unsolved. We analyzed the expression of podocyte proteins in two kidney disorders: Congenital nephrotic syndrome of the Finnish type (CNF) and minimal change nephrotic syndrome (MCNS). METHODS: Immunoperoxidase and immunofluorescence stainings were used to semiquantitatively analyze the expression of 13 and 4 podocyte proteins from different cellular compartments in CNF and MCNS, respectively. RESULTS: The expression of a major slit diaphragm (SD) protein, Neph 1, showed a 46-fold decrease (p < 0.0001) in CNF kidneys as compared to controls. The three cytosolic adaptor proteins, podocin, NCK1/2, CD2AP, connecting SD proteins to the actin cytoskeleton were slightly upregulated (1.1-fold, 1.4-fold, and 3.3-fold, respectively). Also, the staining of the two actin-regulator proteins, ACTN4 and INF2, was modestly increased (2.2-fold and 1.7-fold, respectively, p < 0.0001). Staining for alpha3-integrin showed 1.9-fold increase (p < 0.0001) indicating that the major podocyte anchoring complex, alpha3beta1, was well preserved in CNF glomeruli. In contrast to CNF kidneys, Neph1 FAT1, ACTN4, and CD2AP were quite normally expressed in proteinuric and non-proteinuric MCNS kidneys. CONCLUSION: CNF kidneys lacking nephrin show decreased expression of other SD proteins but not cytosolic podocyte proteins involved in the foot process architecture or function. In MCNS kidneys, these changes in expression were not observed. PMID- 25117491 TI - Correlation of gross urine color with diagnostic findings in male cats with naturally occurring urethral obstruction. AB - Seventy-five male cats with urethral obstruction were prospectively enrolled to evaluate gross urine color at urinary catheter placement for correlation with diagnostic findings. Cats with darker red urine were more likely to be azotemic (serum creatinine concentration >2.0 mg/dl [177 umol/l]), and urine color correlated well with serum creatinine and serum potassium concentrations. Darker urine color was negatively correlated with urine specific gravity. Urine color was not associated with the presence or absence of lower urinary tract stones on radiographs or ultrasound. Cats with darker red urine at the time of urinary catheter placement are likely to have more significant metabolic derangements and may require more aggressive supportive care. PMID- 25117489 TI - A long non-coding RNA is required for targeting centromeric protein A to the human centromere. AB - The centromere is a specialized chromatin region marked by the histone H3 variant CENP-A. Although active centromeric transcription has been documented for over a decade, the role of centromeric transcription or transcripts has been elusive. Here, we report that centromeric alpha-satellite transcription is dependent on RNA Polymerase II and occurs at late mitosis into early G1, concurrent with the timing of new CENP-A assembly. Inhibition of RNA Polymerase II-dependent transcription abrogates the recruitment of CENP-A and its chaperone HJURP to native human centromeres. Biochemical characterization of CENP-A associated RNAs reveals a 1.3 kb molecule that originates from centromeres, which physically interacts with the soluble pre-assembly HJURP/CENP-A complex in vivo, and whose down-regulation leads to the loss of CENP-A and HJURP at centromeres. This study describes a novel function for human centromeric long non-coding RNAs in the recruitment of HJURP and CENP-A, implicating RNA-based chaperone targeting in histone variant assembly. PMID- 25117492 TI - Ionophore-based ion-selective optical nanosensors operating in exhaustive sensing mode. AB - Ion selective optical sensors are typically interrogated under conditions where the sample concentration is not altered during measurement. We describe here an alternative exhaustive detection mode for ion selective optical sensors. This exhaustive sensor concept is demonstrated with ionophore-based nanooptodes either selective for calcium or the polycationic heparin antidote protamine. In agreement with a theoretical treatment presented here, linear calibration curves were obtained in the exhaustive detection mode instead of the sigmoidal curves for equilibrium-based sensors. The response range can be tuned by adjusting the nanosensor loading. The nanosensors showed average diameters of below 100 nm and the sensor response was found to be dramatically faster than that for film-based optodes. Due to the strong binding affinity of the exhaustive nanosensors, total calcium concentration in human blood plasma was successfully determined. Optical determination of protamine in human blood plasma using the exhaustive nanosensors was attempted, but was found to be less successful. PMID- 25117493 TI - Genotoxic effects of water pollution on two fish species living in Karasu River, Erzurum, Turkey. AB - Karasu River, which is the only river in the Erzurum plain, is the source of the Euphrates River (Eastern Anatolia of Turkey). The river is in a serious environmental situation as a result of pollution by agricultural and industrial sewage and domestic discharges. The present study aims to evaluate genotoxic effects of toxic metals in chub, Leuciscus cephalus, and transcaucasian barb, Capoeta capoeta, collected from contaminated site of the Karasu River, in comparison with fish from an unpolluted reference site. Heavy metal concentrations in surface water of the river were determined. The condition factor (CF) was taken as a general biomarker of the health of the fish, and genotoxicity assays such as micronucleus (MN) and other nuclear abnormalities (NA) were carried out on the fish species studied. MN and NA such as kidney shaped nucleus, notched nucleus, binucleated, lobed nucleus, and blebbed nucleus were assessed in peripheral blood erythrocytes, gill epithelial cells, and liver cells of the fish. A significant decrease in CF values associated with a significant elevation in MN and NA frequencies was observed in fish collected from the polluted sites compared with those from the reference site. Results of the current study show the significance of integrating a set of biomarkers to identify the effects of anthropogenic pollution. High concentrations of heavy metals have a potential genotoxic effects, and the toxicity is possibly related to industrial, agricultural, and domestic activities. PMID- 25117494 TI - Geospatial assessment and monitoring of historical forest cover changes (1920 2012) in Nilgiri Biosphere Reserve, Western Ghats, India. AB - Deforestation in the biosphere reserves, which are key Protected Areas has negative impacts on biodiversity, climate, carbon fluxes and livelihoods. Comprehensive study of deforestation in biosphere reserves is required to assess the impact of the management effectiveness. This article assesses the changes in forest cover in various zones and protected areas of Nilgiri Biosphere Reserve, the first declared biosphere reserve in India which forms part of Western Ghats-a global biodiversity hotspot. In this study, we have mapped the forests from earliest available topographical maps and multi-temporal satellite data spanning from 1920's to 2012 period. Mapping of spatial extent of forest cover, vegetation types and land cover was carried out using visual interpretation technique. A grid cell of 1 km * 1 km was generated for time series change analysis to understand the patterns in spatial distribution of forest cover (1920-1973-1989 1999-2006-2012). The total forest area of biosphere reserve was found to be 5,806.5 km(2) (93.8 % of total geographical area) in 1920. Overall loss of forest cover was estimated as 1,423.6 km(2) (24.5 % of the total forest) with reference to 1920. Among the six Protected Areas, annual deforestation rate of >0.5 was found in Wayanad wildlife sanctuary during 1920-1973. The deforestation in Nilgiri Biosphere Reserve is mainly attributed to conversion of forests to plantations and agriculture along with submergence due to construction of dams during 1920 to 1989. Grid wise analysis indicates that 851 grids have undergone large-scale negative changes of >75 ha of forest loss during 1920-1973 while, only 15 grids have shown >75 ha loss during 1973-1989. Annual net rate of deforestation for the period of 1920 to 1973 was calculated as 0.5 followed by 0.1 for 1973 to 1989. Our analysis shows that there was large-scale deforestation before the declaration of area as biosphere reserve in 1986; however, the deforestation has drastically reduced after the declaration due to high degree of protection, thus indicating the secure future of reserve in the long term under the current forest management practices. The present work will stand as the most up-to-date assessment on the forest cover of the Nilgiri Biosphere Reserve with immediate applications in monitoring and management of forest biodiversity. PMID- 25117490 TI - DNA binding polarity, dimerization, and ATPase ring remodeling in the CMG helicase of the eukaryotic replisome. AB - The Cdc45/Mcm2-7/GINS (CMG) helicase separates DNA strands during replication in eukaryotes. How the CMG is assembled and engages DNA substrates remains unclear. Using electron microscopy, we have determined the structure of the CMG in the presence of ATPgammaS and a DNA duplex bearing a 3' single-stranded tail. The structure shows that the MCM subunits of the CMG bind preferentially to single stranded DNA, establishes the polarity by which DNA enters into the Mcm2-7 pore, and explains how Cdc45 helps prevent DNA from dissociating from the helicase. The Mcm2-7 subcomplex forms a cracked-ring, right-handed spiral when DNA and nucleotide are bound, revealing unexpected congruencies between the CMG and both bacterial DnaB helicases and the AAA+ motor of the eukaryotic proteasome. The existence of a subpopulation of dimeric CMGs establishes the subunit register of Mcm2-7 double hexamers and together with the spiral form highlights how Mcm2-7 transitions through different conformational and assembly states as it matures into a functional helicase. PMID- 25117495 TI - Mercury speciation in plankton from the Cabo Frio Bay, SE--Brazil. AB - Mercury (Hg) is considered a global pollutant, and the scientific community has shown great concern about its toxicity as it may affect the biota of entire systems, through bioaccumulation and bioamplification processes of its organic form, methylmercury (MeHg), along food web. However, few research studies deal with bioaccumulation of Hg from marine primary producers and the first-order consumers. So, this study aims to determine Hg distribution and concentration levels in phytoplankton and zooplankton in the Cabo Frio Bay, Brazil, a site influenced by coastal upwelling. The results from Hg speciation analyses show that inorganic mercury Hg(II) was the predominant specie in plankton from this bay. The annual Hg species distribution in plankton shown mean concentration of 2.00 +/- 1.28 ng Hg(II) g(-1) and 0.15 +/- 0.08 ng MeHg g(-1) wet weight (phytoplankton) and 2.5 +/- 2.03 ng Hg(II) g(-1) and 0.25 +/- 0.09 ng MeHg g(-1) wet weight (zooplankton). Therefore, upwelling zones should be considered in the Hg biogeochemical cycle models as a process that enhances Hg(II) bioaccumulation in plankton, raising its bioavailability and shelf deposition. PMID- 25117496 TI - Extensive transcription analysis of the Hyposoter didymator Ichnovirus genome in permissive and non-permissive lepidopteran host species. AB - Ichnoviruses are large dsDNA viruses that belong to the Polydnaviridae family. They are specifically associated with endoparasitic wasps of the family Ichneumonidae and essential for host parasitization by these wasps. We sequenced the Hyposoter didymator Ichnovirus (HdIV) encapsidated genome for further analysis of the transcription pattern of the entire set of HdIV genes following the parasitization of four different lepidopteran host species. The HdIV genome was found to consist of at least 50 circular dsDNA molecules, carrying 135 genes, 98 of which formed 18 gene families. The HdIV genome had general features typical of Ichnovirus (IV) genomes and closely resembled that of the IV carried by Hyposoter fugitivus. Subsequent transcriptomic analysis with Illumina technology during the course of Spodoptera frugiperda parasitization led to the identification of a small subset of less than 30 genes with high RPKM values in permissive hosts, consisting with these genes encoding crucial virulence proteins. Comparisons of HdIV expression profiles between host species revealed differences in transcript levels for given HdIV genes between two permissive hosts, S. frugiperda and Pseudoplusia includens. However, we found no evident intrafamily gene-specific transcription pattern consistent with the presence of multigenic families within IV genomes reflecting an ability of the wasps concerned to exploit different host species. Interestingly, in two non-permissive hosts, Mamestra brassiccae and Anticarsia gemmatalis (most of the parasitoid eggs were eliminated by the host cellular immune response), HdIV genes were generally less strongly transcribed than in permissive hosts. This suggests that successful parasitism is dependent on the expression of given HdIV genes exceeding a particular threshold value. These results raise questions about the mecanisms involved in regulating IV gene expression according to the nature of the lepidopteran host species encountered. PMID- 25117499 TI - Advantages of crystallographic fragment screening: functional and mechanistic insights from a powerful platform for efficient drug discovery. AB - X-ray crystallography has been an under-appreciated screening tool for fragment based drug discovery due to the perception of low throughput and technical difficulty. Investigators in industry and academia have overcome these challenges by taking advantage of key factors that contribute to a successful crystallographic screening campaign. Efficient cocktail design and soaking methodologies have evolved to maximize throughput while minimizing false positives/negatives. In addition, technical improvements at synchrotron beamlines have dramatically increased data collection rates thus enabling screening on a timescale comparable to other techniques. The combination of available resources and efficient experimental design has resulted in many successful crystallographic screening campaigns. The three-dimensional crystal structure of the bound fragment complexed to its target, a direct result of the screening effort, enables structure-based drug design while revealing insights regarding protein dynamics and function not readily obtained through other experimental approaches. Furthermore, this "chemical interrogation" of the target protein crystals can lead to the identification of useful reagents for improving diffraction resolution or compound solubility. PMID- 25117500 TI - Field-dependent anisotropic microrheological and microstructural properties of dilute ferrofluids. AB - We have measured microrheological and microstructural properties of a superparamagnetic ferrofluid made of Mn0.75Zn0.25Fe2O4 (MZF) nanoparticles, using passive microrheology in a home-built inverted microscope. Thermal motion of a probe microsphere was measured for different values of an applied external magnetic field and analysed. The analysis shows anisotropy in magneto-viscous effect. Additional microrheological properties, such as storage modulus and loss modulus and their transition are also seen. We have also obtained microstructural properties such as elongational flow coefficient [Formula: see text] , relaxation time constant [Formula: see text] , coefficient of dissipative magnetization [Formula: see text] , etc., using the analysis given in Oliver Muller et al., J. Phys.: Condens. Matter 18, S2623, (2006) and Stefan Mahle et al., Phys. Rev. E 77, 016305 (2008) over our measured viscosity data. Our values for the above parameters are in agreement with earlier theoretical calculations and macro rheological experimental measurements. These theoretical calculations consider an ideal situation of zero-shear limit, which is best approximated only in the passive microrheology technique described here and a first time measurement of all these parameters with passive microrheology. PMID- 25117501 TI - Elasticity and mechanical instability of charged lipid bilayers in ionic solutions. AB - We use coarse-grained Monte Carlo simulations to study the elastic properties of charged membranes in solutions of monovalent and pentavalent counterions. The simulation results of the two cases reveal trends opposite to each other. The bending rigidity and projected area increase with the membrane charge density for monovalent counterions, while they decrease for the pentavalent ions. These observations can be related to the counterion screening of the lipid charges. While the monovalent counterions only weakly screen the Coulomb interactions, which implies a repulsive Coulomb system, the multivalent counterions condense on the membrane and, through spatial charge correlations, make the effective interactions due to the charged lipids attractive. The differences in the elastic properties of the charged membranes in monovalent and multivalent counterion solutions are reflected in the mechanisms leading to their mechanical instability at high charge densities. In the former case, the membranes develop pores to relieve the electrostatic tensile stresses, while in the latter case, the membrane exhibits large wavelength bending instability. PMID- 25117502 TI - Cancer genetic testing panels for inherited cancer susceptibility: the clinical experience of a large adult genetics practice. AB - Next-generation sequencing genetic testing panels for cancer susceptibility (cancer panels) have recently become clinically available. At present, clinical utility is unknown and there are no set criteria or guidelines established for whom to offer such testing. Although it may be a cost-effective method to test multiple cancer susceptibility genes concurrently, the rate of finding variants of unknown significance (VUS) may be high and testing may yield mutations in genes with no established management recommendations. We describe our Center's experience over a 14-month period (April 2012-June 2013) for patient interest and uptake in cancer panel testing and whether there were predictors of pursuing testing or identifying mutations. Using a clinical ranking system, patients' family histories were ranked from 0 to 3 (low likelihood to high likelihood for underlying genetic susceptibility). The clinical ranking system was assessed to determine its predictability of finding mutations. Of the 689 patients who met inclusion criteria, the option of pursuing a cancer panel was discussed with 357 patients; 63 (17.6 %) patients pursued testing. Those who pursued testing were more likely to be older, male, affected with cancer, affected with multiple primary cancers, and had a higher clinical rank than non-pursuers. There were no significant predictors of finding a mutation on panel testing. Of the 61 patients who have received results, there was a 6.6 % mutation rate and 19.7 % VUS rate. The yield of cancer panels in clinical practice is low and the strength of family history alone may not predict likelihood of finding a mutation. PMID- 25117498 TI - Interrogation of living myocardium in multiple static deformation states with diffusion tensor and diffusion spectrum imaging. AB - Diffusion tensor magnetic resonance imaging (MRI) reveals valuable insights into tissue histo-anatomy and microstructure, and has steadily gained traction in the cardiac community. Its wider use in small animal cardiac imaging in vivo has been constrained by its extreme sensitivity to motion, exaggerated by the high heart rates usually seen in rodents. Imaging of the isolated heart eliminates respiratory motion and, if conducted on arrested hearts, cardiac pulsation. This serves as an important intermediate step for basic and translational studies. However, investigating the micro-structural basis of cardiac deformation in the same heart requires observations in different deformation states. Here, we illustrate the imaging of isolated rat hearts in three mechanical states mimicking diastole (cardioplegic arrest), left-ventricular (LV) volume overload (cardioplegic arrest plus LV balloon inflation), and peak systole (lithium induced contracture). An optimised MRI-compatible Langendorff perfusion setup with the radio-frequency (RF) coil integrated into the wet chamber was developed for use in a 9.4T horizontal bore scanner. Signal-to-noise ratio improved significantly, by 75% compared to a previous design with external RF coil, and stability tests showed no significant changes in mean T1, T2 or LV wall thickness over a 170 min period. In contracture, we observed a significant reduction in mean fractional anisotropy from 0.32 +/- 0.02 to 0.28 +/- 0.02, as well as a significant rightward shift in helix angles with a decrease in the proportion of left-handed fibres, as referring to the locally prevailing cell orientation in the heart, from 24.9% to 23.3%, and an increase in the proportion of right-handed fibres from 25.5% to 28.4%. LV overload, in contrast, gave rise to a decrease in the proportion of left-handed fibres from 24.9% to 21.4% and an increase in the proportion of right-handed fibres from 25.5% to 26.0%. The modified perfusion and coil setup offers better performance and control over cardiac contraction states. We subsequently performed high-resolution diffusion spectrum imaging (DSI) and 3D whole heart fibre tracking in fixed ex vivo rat hearts in slack state and contracture. As a model-free method, DSI augmented the measurements of water diffusion by also informing on multiple intra-voxel diffusion orientations and non-Gaussian diffusion. This enabled us to identify the transition from right- to left-handed fibres from the subendocardium to the subepicardium, as well as voxels in apical regions that were traversed by multiple fibres. We observed that both the mean generalised fractional anisotropy and mean kurtosis were lower in hearts in contracture compared to the slack state, by 23% and 9.3%, respectively. While its heavy acquisition burden currently limits the application of DSI in vivo, ongoing work in acceleration techniques may enable its use in live animals and patients. This would provide access to the as yet unexplored dimension of non Gaussian diffusion that could serve as a highly sensitive marker of cardiac micro structural integrity. PMID- 25117497 TI - Images as drivers of progress in cardiac computational modelling. AB - Computational models have become a fundamental tool in cardiac research. Models are evolving to cover multiple scales and physical mechanisms. They are moving towards mechanistic descriptions of personalised structure and function, including effects of natural variability. These developments are underpinned to a large extent by advances in imaging technologies. This article reviews how novel imaging technologies, or the innovative use and extension of established ones, integrate with computational models and drive novel insights into cardiac biophysics. In terms of structural characterization, we discuss how imaging is allowing a wide range of scales to be considered, from cellular levels to whole organs. We analyse how the evolution from structural to functional imaging is opening new avenues for computational models, and in this respect we review methods for measurement of electrical activity, mechanics and flow. Finally, we consider ways in which combined imaging and modelling research is likely to continue advancing cardiac research, and identify some of the main challenges that remain to be solved. PMID- 25117504 TI - CT angiography after carotid artery stenting: assessment of the utility of adaptive statistical iterative reconstruction and model-based iterative reconstruction. AB - INTRODUCTION: Follow-up CT angiography (CTA) is routinely performed for post procedure management after carotid artery stenting (CAS). However, the stent lumen tends to be underestimated because of stent artifacts on CTA reconstructed with the filtered back projection (FBP) technique. We assessed the utility of new iterative reconstruction techniques, such as adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR), for CTA after CAS in comparison with FBP. METHODS: In a phantom study, we evaluated the differences among the three reconstruction techniques with regard to the relationship between the stent luminal diameter and the degree of underestimation of stent luminal diameter. In a clinical study, 34 patients who underwent follow up CTA after CAS were included. We compared the stent luminal diameters among FBP, ASIR, and MBIR, and performed visual assessment of low attenuation area (LAA) in the stent lumen using a three-point scale. RESULTS: In the phantom study, stent luminal diameter was increasingly underestimated as luminal diameter became smaller in all CTA images. Stent luminal diameter was larger with MBIR than with the other reconstruction techniques. Similarly, in the clinical study, stent luminal diameter was larger with MBIR than with the other reconstruction techniques. LAA detectability scores of MBIR were greater than or equal to those of FBP and ASIR in all cases. CONCLUSION: MBIR improved the accuracy of assessment of stent luminal diameter and LAA detectability in the stent lumen when compared with FBP and ASIR. We conclude that MBIR is a useful reconstruction technique for CTA after CAS. PMID- 25117503 TI - High prevalence of mismatch repair deficiency in prostate cancers diagnosed in mismatch repair gene mutation carriers from the colon cancer family registry. AB - The question of whether prostate cancer is part of the Lynch syndrome spectrum of tumors is unresolved. We investigated the mismatch repair (MMR) status and pathologic features of prostate cancers diagnosed in MMR gene mutation carriers. Prostate cancers (mean age at diagnosis = 62 +/- SD = 8 years) from 32 MMR mutation carriers (23 MSH2, 5 MLH1 and 4 MSH6) enrolled in the Australasian, Mayo Clinic and Ontario sites of the Colon Cancer Family Registry were examined for clinico-pathologic features and MMR-deficiency (immunohistochemical loss of MMR protein expression and high levels of microsatellite instability; MSI-H). Tumor MMR-deficiency was observed for 22 cases [69 %; 95 % confidence interval (CI) 50 83 %], with the highest prevalence of MMR-deficiency in tumors from MSH2 mutation carriers (19/23, 83 %) compared with MLH1 and MSH6 carriers combined (3/9, 33 %; p = 0.01). MMR-deficient tumors had increased levels of tumor infiltrating lymphocytes compared with tumors without MMR-deficiency (p = 0.04). Under the assumption that tumour MMR-deficiency occurred only because the cancer was caused by the germline mutation, mutation carriers are at 3.2-fold (95 % CI 2.0-6.3) increased risk of prostate cancer, and when assessed by gene, the relative risk was greatest for MSH2 carriers (5.8, 95 % CI 2.6-20.9). Prostate cancer was the first or only diagnosed tumor in 37 % of carriers. MMR gene mutation carriers have at least a twofold or greater increased risk of developing MMR-deficient prostate cancer where the risk is highest for MSH2 mutation carriers. MMR IHC screening of prostate cancers will aid in identifying MMR gene mutation carriers. PMID- 25117506 TI - Intake and macronutrient content of human milk given to extremely preterm infants. AB - BACKGROUND: Human milk (HM) is the preferred basis of nutrition for infants, including those born prematurely. Information on HM macronutrient content is necessary to optimize nutritional support of preterm infants. OBJECTIVES: This study aimed to describe the types and amounts of enteral feeds given to Swedish extremely preterm infants during hospitalization and to investigate the energy and macronutrient contents in HM given to these infants. METHODS: A population based study of Swedish extremely preterm infants (n = 586) born before 27 gestational weeks was conducted. Data on ingested volumes of different milk during hospitalization and analyses of macronutrient content in HM samples were obtained from hospital records. Nutritional content of HM was determined by mid infrared spectrophotometry analysis. RESULTS: During the first 4 weeks of life, 99% of the infants were exclusively fed HM, and at 4 weeks of life, 70% of the infants received only mother's own milk (MOM). Nutritional content in 821 MOM samples was analyzed. Protein content in MOM decreased significantly from 2.2 to 1.2 g/100 mL during the first 112 postpartum days, whereas fat and energy content were highly variable within and between MOM samples. In addition, 354 samples of donor milk were analyzed. Content of protein, fat, and energy in pooled donor milk (n = 129) was lower compared to single donor milk. CONCLUSION: Swedish extremely preterm infants receive MOM to a large extent during hospitalization. Protein, carbohydrates, and energy in MOM changed significantly with time. Weekly analyses of MOM during the first month of lactation would allow more individualized nutritional support for these vulnerable infants. PMID- 25117505 TI - Sinupret activates CFTR and TMEM16A-dependent transepithelial chloride transport and improves indicators of mucociliary clearance. AB - INTRODUCTION: We have previously demonstrated that Sinupret, an established treatment prescribed widely in Europe for respiratory ailments including rhinosinusitis, promotes transepithelial chloride (Cl-) secretion in vitro and in vivo. The present study was designed to evaluate other indicators of mucociliary clearance (MCC) including ciliary beat frequency (CBF) and airway surface liquid (ASL) depth, but also investigate the mechanisms that underlie activity of this bioflavonoid. METHODS: Primary murine nasal septal epithelial (MNSE) [wild type (WT) and transgenic CFTR(-/-)], human sinonasal epithelial (HSNE), WT CFTR expressing CFBE and TMEM16A-expressing HEK cultures were utilized for the present experiments. CBF and ASL depth measurements were performed. Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers, Fura-2 intracellular calcium [Ca(2+)]i imaging, cAMP signaling, regulatory domain (R-D) phosphorylation of CFTR, and excised inside out and whole cell patch clamp analysis. RESULTS: Sinupret-mediated Cl- secretion [DeltaISC(uA/cm(2))] was pronounced in WT MNSE (20.7+/-0.9 vs. 5.6+/ 0.9(control), p<0.05), CFTR(-/-) MNSE (10.1+/-1.0 vs. 0.9+/-0.3(control), p<0.05) and HSNE (20.7+/-0.3 vs. 6.4+/-0.9(control), p<0.05). The formulation activated Ca(2+) signaling and TMEM16A channels, but also increased CFTR channel open probability (Po) without stimulating PKA-dependent pathways responsible for phosphorylation of the CFTR R-domain and resultant Cl- secretion. Sinupret also enhanced CBF and ASL depth. CONCLUSION: Sinupret stimulates CBF, promotes transepithelial Cl- secretion, and increases ASL depth in a manner likely to enhance MCC. Our findings suggest that direct stimulation of CFTR, together with activation of Ca(2+)-dependent TMEM16A secretion account for the majority of anion transport attributable to Sinupret. These studies provide further rationale for using robust Cl- secretagogue based therapies as an emerging treatment modality for common respiratory diseases of MCC including acute and chronic bronchitis and CRS. PMID- 25117507 TI - Polymorphisms of E1 and GIGANTEA in wild populations of Lotus japonicus. AB - In plants, timing of flowering is an essential factor that controls the survival rates of descendants. The circadian clock genes E1 and GIGANTEA (GI) play a central role in transmitting signals to flowering locus T (FT) in leguminous plants. Lotus japonicus is a wild Japanese species that ranges from northern Hokkaido to the southern Ryukyus and exhibits a wide range in terms of the time between seeding and first flowering. In this study, we first identified LjGI and analyzed polymorphisms of LjE1 and LjGI among wild populations covering the entire distribution range of this species in Japan. LjGI had a coding sequence (CDS) length of 3495 bp and included 14 exons. The homologies of DNA and amino acid sequences between LjGI and GmGI were 89 and 88% (positive rate was 92%), respectively. LjE1 harbored five nucleic acid changes in a 552 bp CDS, all of which were nonsynonymous; four of the changes were located in the core function area. LjE1 alleles exhibited partial north-south differentiation and non neutrality. In contrast, the LjGI harbored one synonymous and one nonsynonymous change. Thus, our study suggests that LjE1 may be involved in the control of flowering times, whereas LjGI may be under strong purifying selection. PMID- 25117509 TI - Toward absolute chemical composition distribution measurement of polyolefins by high-temperature liquid chromatography hyphenated with infrared absorbance and light scattering detectors. AB - Chemical composition distribution (CCD) is a fundamental metric for representing molecular structures of copolymers in addition to molecular weight distribution (MWD). Solvent gradient interaction chromatography (SGIC) is commonly used to separate copolymers by chemical composition in order to obtain CCD. The separation of polymer in SGIC is, however, not only affected by chemical composition but also by molecular weight and architecture. The ability to measure composition and MW simultaneously after separation would be beneficial for understanding the impact of different factors and deriving true CCD. In this study, comprehensive two-dimensional chromatography (2D) was coupled with infrared absorbance (IR5) and light scattering (LS) detectors for characterization of ethylene-propylene copolymers. Polymers were first separated by SGIC as the first dimension chromatography (D1). The separated fractions were then characterized by the second dimension (D2) size exclusion chromatography (SEC) with IR5 and LS detectors. The concentrations and compositions of the separated fractions were measured online using the IR5 detector. The MWs of the fractions were measured by the ratio of LS to IR5 signals. A metric was derived from online concentration and composition data to represent CCD breadth. The metric was shown to be independent of separation gradients for an "absolute" measurement of CCD breadth. By combining online composition and MW data, the relationship of MW as a function of chemical composition was obtained. This relationship was qualitatively consistent with the results by SEC coupled to IR5, which measures chemical composition as a function of logMW. The simultaneous measurements of composition and MW give the opportunity to study the SGIC separation mechanism and derive chain architectural characteristics of polymer chains. PMID- 25117508 TI - Two HSPs gene from juvenile Amur sturgeon (Acipenser schrenckii): cloning, characterization and expression pattern to crowding and hypoxia stress. AB - In this study, the cDNA sequences of HSP70 and HSP90 were isolated from the special chondr-ganoid scale, Amur sturgeon, for the first time. Homology analysis indicated that amino acid sequences of HSP70 and HSP90 shared high identity with other species (82.68-99.07 and 90.19-98.07%, respectively). The tissue expression analysis showed that the asHSP70 and asHSP90 mRNA were ubiquitously expressed in all the examined tissues under unstressed condition. The expression pattern of HSP70 and HSP90 under chronic (crowding) and acute (hypoxia) stress was examined by q-PCR in liver, spleen and kidney. Results showed that stocking density could significantly influence the expression of HSP70 at day 20 and/or day 40. In contrast to stocking density, levels of HSP70 transcripts indicated a remarkable increase in all examined tissues after hypoxia stress. HSP90 levels in liver and spleen increased significantly in high stocking density. By comparison, significant increase of asHSP90 in kidney was only found in high stocking density at day 40. Similar to HSP70, the levels of HSP90 transcripts showed significant increases after hypoxia stress except the transcript of liver in H2 group 6 h after hypoxia. The assessment of asHSP70 and asHSP90 mRNA levels under crowding and hypoxia stresses indicated that asHSP70 and asHSP90 gene might be good indicators of stressful situations for Amur sturgeon. Taking serum globulin and electrolytes account, we suggest that crowding and hypoxia stress can result in considerable stress for Amur sturgeon. PMID- 25117510 TI - Curcumin supplementation improves mitochondrial and behavioral deficits in experimental model of chronic epilepsy. AB - The present study was aimed to investigate the potential beneficial effect of curcumin, a polyphenol with pleiotropic properties, on mitochondrial dysfunctions, oxidative stress and cognitive deficits in a kindled model of epilepsy. Kindled epilepsy was induced in rats by administering a sub-convulsive dose of pentylenetetrazole (PTZ, 40 mg/kg body weight) every alternate day for 30 days. PTZ administered rats exhibited marked cognitive deficits assessed using active and passive avoidance tasks. This was accompanied by a significant decrease in NADH:cytochrome-c reductase (complex I) and cytochrome-c oxidase (complex IV) activities along with an increase in ROS, lipid peroxidation and protein carbonyls. The levels of glutathione also decreased in the cortex and hippocampus. Electron micrographs revealed disruption of mitochondrial membrane integrity with distorted cristae in PTZ treated animals. Histopathological examination showed pyknotic nuclei and cell loss in the hippocampus as well as in the cortex of PTZ treated animals. Curcumin administration at a dose of 100 mg/kg, p.o. throughout the treatment paradigm was able to ameliorate cognitive deficits with no significant effect on seizure score. Curcumin was able to restore the activity of mitochondrial complexes. In addition, significant reduction in ROS generation, lipid peroxidation and protein carbonyls was observed in PTZ animals supplemented with curcumin. Moreover, glutathione levels were also restored in PTZ treated rats supplemented with curcumin. Curcumin protected mitochondria from seizure induced structural alterations. Further, the curcumin supplemented PTZ rats had normal cell morphology and reduced cell loss. These results suggest that curcumin supplementation has potential to prevent mitochondrial dysfunctions and oxidative stress with improved cognitive functions in a chronic model of epilepsy. PMID- 25117512 TI - Texture feature analysis for computer-aided diagnosis on pulmonary nodules. AB - Differentiation of malignant and benign pulmonary nodules is of paramount clinical importance. Texture features of pulmonary nodules in CT images reflect a powerful character of the malignancy in addition to the geometry-related measures. This study first compared three well-known types of two-dimensional (2D) texture features (Haralick, Gabor, and local binary patterns or local binary pattern features) on CADx of lung nodules using the largest public database founded by Lung Image Database Consortium and Image Database Resource Initiative and then investigated extension from 2D to three-dimensional (3D) space. Quantitative comparison measures were made by the well-established support vector machine (SVM) classifier, the area under the receiver operating characteristic curves (AUC) and the p values from hypothesis t tests. While the three feature types showed about 90% differentiation rate, the Haralick features achieved the highest AUC value of 92.70% at an adequate image slice thickness, where a thinner or thicker thickness will deteriorate the performance due to excessive image noise or loss of axial details. Gain was observed when calculating 2D features on all image slices as compared to the single largest slice. The 3D extension revealed potential gain when an optimal number of directions can be found. All the observations from this systematic investigation study on the three feature types can lead to the conclusions that the Haralick feature type is a better choice, the use of the full 3D data is beneficial, and an adequate tradeoff between image thickness and noise is desired for an optimal CADx performance. These conclusions provide a guideline for further research on lung nodule differentiation using CT imaging. PMID- 25117513 TI - Fetal echocardiography has a role in multimodality imaging for surgical planning. PMID- 25117514 TI - Saccharomyces cerevisiae Gpi2, an accessory subunit of the enzyme catalyzing the first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis, selectively complements some of the functions of its homolog in Candida albicans. AB - GPI2 encodes for one of the six accessory subunits of the GPI-N acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the first step of GPI biosynthesis in S. cerevisiae and C. albicans. It has been previously reported in S. cerevisiae that this subunit physically interacts with and negatively modulates Ras signaling. On the other hand, studies from our lab have shown that the homologous subunit in C. albicans is a positive modulator of Ras signaling. Are the functions of this subunit therefore strictly species dependent? We present here functional complementation studies on GPI2 from S. cerevisiae and C. albicans that were carried out to address this issue. Expression of CaGPI2 in a ScGPI2 conditional lethal mutant could not restore its growth defects. Likewise, ScGPI2 overexpression in a CaGPI2 heterozygous mutant could not restore its deficient GPI-GnT activity or reverse defects in its cell wall integrity and could only poorly restore filamentation. However, interestingly, ScGPI2 could restore lanosterol demethylase (CaERG11) levels and reverse azole resistance of the CaGPI2 heterozygote. It appeared to do this by regulating levels of another GPI-GnT subunit, CaGPI19, which we have previously shown to be involved in cross-talk with CaERG11. Thus, the effect of CaGPI2 on sterol biosynthesis in C. albicans is independent of its interaction with the GPI GnT complex and Ras signaling pathways. In addition, the interaction of Gpi2 with other subunits of the GPI-GnT complex as well as with Ras signaling appears to have evolved differently in the two organisms. PMID- 25117515 TI - Flexibility and mutagenic resiliency of glycosyltransferases. AB - The human blood group A and B antigens are synthesized by two highly homologous enzymes, glycosyltransferase A (GTA) and glycosyltransferase B (GTB), respectively. These enzymes catalyze the transfer of either GalNAc or Gal from their corresponding UDP-donors to alphaFuc1-2betaGal-R terminating acceptors. GTA and GTB differ at only four of 354 amino acids (R176G, G235S, L266M, G268A), which alter the donor specificity from UDP-GalNAc to UDP-Gal. Blood type O individuals synthesize truncated or non-functional enzymes. The cloning, crystallization and X-ray structure elucidations for GTA and GTB have revealed key residues responsible for donor discrimination and acceptor binding. Structural studies suggest that numerous conformational changes occur during the catalytic cycle. Over 300 ABO alleles are tabulated in the blood group antigen mutation database (BGMUT) that provides a framework for structure-function studies. Natural mutations are found in all regions of GTA and GTB from the active site, flexible loops, stem region and surfaces remote from the active site. Our characterizations of natural mutants near a flexible loop (V175M), on a remote surface site (P156L), in the metal binding motif (M212V) and near the acceptor binding site (L232P) demonstrate the resiliency of GTA and GTB to mutagenesis. PMID- 25117517 TI - Calibration-free ionophore-based ion-selective electrodes with a Co(II)/Co(III) redox couple-based solid contact. AB - A high electrode-to-electrode reproducibility of the emf response of solid contact ion-selective electrodes (SC-ISEs) requires a precise control of the phase boundary potential between the ion-selective membrane (ISM) and the underlying electron conductor. To achieve this, we introduced previously ionophore-free ion exchanger membranes doped with a well controlled ratio of oxidized and reduced species of a redox couple as redox buffer and used them to make SC-ISEs that exhibited highly reproducible electrode-to-electrode potentials. Unfortunately, ionophores were found to promote the loss of insufficiently lipophilic species from the ionophore-doped ISMs into aqueous samples. Here we report on an improved redox buffer platform based on equimolar amounts of the much less hydrophilic Co(III) and Co(II) complexes of 4,4'-dinonyl 2,2'-bipyridyl, which makes it possible to extend the redox buffer approach to ionophore-based ISEs. For example, K(+)-selective electrodes based on the ionophore valinomycin exhibit electrode-to-electrode standard deviations as low as 0.7 mV after exposure of freshly prepared electrodes for 1 h to aqueous solutions. Exposure of freshly prepared ISE membranes to humidity prior to their first contact to electrolyte solution minimizes the initial (reproducible) emf drift. This redox buffer has also been successfully applied to sodium, potassium, calcium, hydrogen, and carbonate ion-selective electrodes, which all exhibit the high selectivity over interfering ions as expected for ionophore-doped ISE membranes. PMID- 25117516 TI - Elucidation of a protein-protein interaction network involved in Corynebacterium glutamicum cell wall biosynthesis as determined by bacterial two-hybrid analysis. AB - Mycobacterium species have a highly complex and unique cell wall that consists of a large macromolecular structure termed the mycolyl-arabinogalactan-peptidoglycan (mAGP) complex. This complex is essential for growth, survival and virulence of the human pathogen Mycobacterium tuberculosis, and is the target of several anti tubercular drugs. The closely related species Corynebacterium glutamicum has proven useful in the study of orthologous M. tuberculosis genes and proteins involved in mAGP synthesis. This study examines the construction of a protein protein interaction network for the major cell wall component arabinogalactan in C. glutamicum based on the use of a bacterial two-hybrid system. We have identified twenty-four putative homotypic and heterotypic protein interactions in vivo. Our results demonstrate an association between glycosyltransferases, GlfT1 and AftB, and interaction between the sub-units of decaprenylphosphoribose epimerase, DprE1 and DprE2. These analyses have also shown that AftB interacts with AftA, which catalyzes the addition of the first three arabinose units onto the galactan chain. Both AftA and AftB associate with other arabinofuranosyltransferases, including Emb and AftC, that elongate and branch the arabinan domain. Moreover, a number of proteins involved in arabinogalactan biosynthesis were shown to form dimers or multimers. These findings provide a useful recourse for understanding the biosynthesis and function of the mycobacterial cell wall, as well as providing new therapeutic targets. PMID- 25117519 TI - Support for a tobacco endgame strategy in 18 European countries. AB - OBJECTIVE: The feasibility of a tobacco endgame strategy, aiming to bring smoking prevalence to near-zero levels, is currently under debate. We provide information on public support for such a strategy in Europe. METHODS: In 2010 we conducted a face-to-face representative survey in 18 European countries (Albania, Austria, Bulgaria, the Czech Republic, Croatia, England, Finland, France, Greece, Hungary, Ireland, Italy, Latvia, Poland, Portugal, Romania, Spain and Sweden). The present analysis is based on 16,947 individuals aged >= 15 years providing information on their attitudes towards a complete ban on the use or sale of tobacco. RESULTS: Overall, 34.9% of adults (32.8% in men and 37.0% in women; p<0.001) supported a complete ban strategy on use or sale of tobacco, 41.2% of never, 29.4% of ex- and 25.6% of current smokers. The highest support was observed in southern Europe (42.5%), followed by eastern (39.1%), northern (27.5%) and western Europe (23.0%; p<0.001). A significant inverse trend was observed with both age and education. CONCLUSION: Approximately one in three adults (and one in four smokers) supports a comprehensive tobacco endgame intervention. This first study in Europe provides a baseline for evaluating future trends in public support for extreme propositions to end or drastically cut smoking. PMID- 25117518 TI - Whole organism high content screening identifies stimulators of pancreatic beta cell proliferation. AB - Inducing beta-cell mass expansion in diabetic patients with the aim to restore glucose homeostasis is a promising therapeutic strategy. Although several in vitro studies have been carried out to identify modulators of beta-cell mass expansion, restoring endogenous beta-cell mass in vivo has yet to be achieved. To identify potential stimulators of beta-cell replication in vivo, we established transgenic zebrafish lines that monitor and allow the quantification of cell proliferation by using the fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology. Using these new reagents, we performed an unbiased chemical screen, and identified 20 small molecules that markedly increased beta-cell proliferation in vivo. Importantly, these structurally distinct molecules, which include clinically-approved drugs, modulate three specific signaling pathways: serotonin, retinoic acid and glucocorticoids, showing the high sensitivity and robustness of our screen. Notably, two drug classes, retinoic acid and glucocorticoids, also promoted beta-cell regeneration after beta-cell ablation. Thus, this study establishes a proof of principle for a high-throughput small molecule-screen for beta-cell proliferation in vivo, and identified compounds that stimulate beta-cell proliferation and regeneration. PMID- 25117520 TI - How personalized medical data could improve health care. AB - We present a redesign of medical test results by placing the information of blood samples in the context of the patient's personal clinical data. We predict that implementing personalized data in the treatment of patients will promote engagement in the treatment, motivate patients to take responsibility and lead to greater satisfaction with the patient-doctor relationship. PMID- 25117521 TI - Patient and physician gender concordance in preventive care in university primary care settings. AB - OBJECTIVE: To assess the quality of preventive care according to physician and patient gender in a country with universal health care coverage. METHODS: We assessed a retrospective cohort study of 1001 randomly selected patients aged 50 80 years followed over 2 years (2005-2006) in 4 Swiss university primary care settings (Basel, Geneva, Lausanne, Zurich). We used indicators derived from RAND's Quality Assessment Tools and examined percentages of recommended preventive care. Results were adjusted using hierarchical multivariate logistic regression models. RESULTS: 1001 patients (44% women) were followed by 189 physicians (52% women). Female patients received less preventive care than male patients (65.2% vs. 72.1%, p<0.001). Female physicians provided significantly more preventive care than male physicians (p=0.01) to both female (66.7% vs. 63.6%) and male patients (73.4% vs. 70.7%). After multivariate adjustment, differences according to physician (p=0.02) and patient gender (p<0.001) remained statistically significant. Female physicians provided more recommended cancer screening than male physicians (78.4 vs. 71.9%, p=0.01). CONCLUSIONS: In Swiss university primary care settings, female patients receive less preventive care than male patients, with female physicians providing more preventive care than male physicians. Greater attention should be paid to female patients in preventive care and to why female physicians tend to provide better preventive care. PMID- 25117522 TI - Understanding occupational sitting: prevalence, correlates and moderating effects in Australian employees. AB - OBJECTIVE: To (1) compare occupational sitting between different socio demographic, health-related, work-related and psychosocial categories, (2) identity socio-demographic, health-related, work-related and psychosocial correlates of occupational sitting, and (3) examine the moderating effect of work related factors in the relation between correlates and occupational sitting. METHODS: Randomly-selected Australian adults completed a web-based survey assessing socio-demographic (country of birth, gender, age, education, income), health-related (general health, weight, physical activity), work-related (employment status, occupational task, occupational classification) and sedentary specific psychosocial (social norm, social support, self-efficacy, control, advantages, disadvantage, intention) factors, and occupational sitting-time. t tests, ANOVAs and multiple linear regression analyses were conducted (in 2013) on a sample of employees (n=993). RESULTS: Respondents sat on average for 3.75 (SD=2.45) h/day during work. Investigated correlates explained 41% of the variance in occupational sitting. More occupational sitting was associated with being male, being younger, higher education and income, part-time and full-time employment, sedentary job tasks, white-collar/professional occupations, higher BMI, and perceiving more advantages of sitting less at work. Employment status and occupational classification moderated the association between control to sit less and occupational sitting. A lack of control to sit less was associated with higher occupational sitting in part-time and full-time workers, but not in casual workers; and in white-collar and professional workers, but not in blue-collar workers. CONCLUSIONS: Most important contributors to occupational sitting were work-related and socio-demographic correlates. More research is needed to confirm present results. PMID- 25117523 TI - The status of men's health in Asia. AB - OBJECTIVES: This study aims to compare health status and its risk factors between men and women who are from countries of different income status in Asia. METHOD: We have included 47 Asian countries and 2 regions in this study. Life expectancy, mortality rate from communicable disease, non-communicable disease and injuries, the prevalence of non-communicable diseases risk factors and their trends were extracted from the WHO and respective governmental database. Subgroup analysis was performed based on country income groups. RESULTS: Overall, men have shorter life expectancy and higher mortality rates compared to women. Men from higher income countries lived longer compared to men from lower-income countries. There is a wide variation of male life expectancy in upper and lower middle income countries. The mean systolic blood pressure, fasting blood glucose and body mass index in Asia have also increased over the years. CONCLUSION: This study confirms that Asian men have poorer health compared to women besides the growing concerns on NCD risk factors. The findings from this study calls for a concerted effort to find solutions in addressing men's health problems in Asia. PMID- 25117524 TI - Dog walking is associated with more outdoor play and independent mobility for children. AB - OBJECTIVE: Dog ownership is positively associated with children's physical activity. It is plausible that dog-facilitated activity rather than dog ownership per se encourages children's physical activity behaviors. We examined relationships between dog walking and children's physical activity, and outdoor play and independent mobility. METHOD: Cross-sectional survey data from the 2007 Perth (Western Australia) TRavel, Environment, and Kids (TREK) project were analyzed for 727 10-12 year olds with a family dog. Weekly minutes of overall physical activity and walking, local walking and outdoor play were collected from children and parents. Children's weekly pedometer steps were measured. Independent mobility was determined by active independent travel to 15 local destinations. RESULTS: Overall, 55% of children walked their dog. After adjustment, more dog walkers than non-dog walkers walked in the neighborhood (75% vs. 47%), played in the street (60% vs. 45%) and played in the yard (91% vs. 84%) (all p <= 0.05). Dog walkers were more independently mobile than non-dog walkers (p <= 0.001). Dog walking status was not associated with overall physical activity, walking, or pedometer steps (p>0.05). CONCLUSIONS: Dog-facilitated play and physical activity can be an effective strategy for increasing children's physical activity. Dog walking may provide a readily accessible and safe option for improving levels of independent mobility. PMID- 25117525 TI - Moving toward implementation: the potential for accountable care organizations and private-public partnerships to advance active neighborhood design. AB - The 2010 Affordable Care Act's (ACA) aims of lowering costs and improving quality of care will renew focus on preventive health strategies. This coincides with a trend in medicine to reconsider population health approaches as part of the standard curriculum. This intersection of new policy and educational climates presents a unique opportunity to reconsider traditional healthcare structures. This paper introduces and advances an alignment that few have considered. We propose that accountable care organizations (ACOs), which are expected to proliferate under the ACA, present the best opportunity to establish partnerships between healthcare, public health, and community-based organizations to achieve the legislation's goals. One example is encouraging daily physical activity via built environment interventions and programs, which is recommended by numerous groups. We highlight how nonprofit organizations in Sacramento, California have been able to leverage influence, capital, and policy to encourage design for active living, and how their work is coordinating with public health and healthcare initiatives. In conclusion, we critically examine potential barriers to the success of partnerships between ACOs and community organizations and encourage further exploration and evaluation. PMID- 25117526 TI - Building safety into active living initiatives. AB - OBJECTIVE: Efforts to promote environmental designs that facilitate opportunities for physical activity should consider the fact that injuries are the leading cause of death for Americans ages 1 to 44, with transportation-related injuries the most common cause. Drawing on the latest research and best practices in the field of injury prevention, the purpose of this article is to provide those working to promote physical activity with evidence-based recommendations on building in safety while designing active environments. METHOD: A systematic review of the peer-reviewed and grey literature published from 1995 to 2012 was conducted to identify injury prevention strategies applicable to objectives in the Active Design Guidelines (ADG), which present design strategies for active living. Injury prevention strategies were rated according to the strength of the research evidence. RESULTS: We identified 18 urban design strategies and 9 building design strategies that promote safety. Evidence was strong or emerging for 14/18 urban design strategies and 7/9 building design strategies. CONCLUSION: ADG strategies are often wholly compatible with well-accepted injury prevention principles. By partnering with architects and planners, injury prevention and public health professionals can help ensure that new and renovated spaces maximize both active living and safety. PMID- 25117528 TI - Quality criteria for health checks: development of a European consensus agreement. AB - OBJECTIVE: Health checks may empower individuals to take better care of their health, but they may incorporate risks of incorrect test results, overdiagnosis and overtreatment as well. Some health checks are strictly regulated, such as in many of the national screening programs, but the ones offered outside such programs and in the commercial domain, are not. We developed a European consensus agreement for quality criteria. METHOD: Quality criteria were developed with the contribution of 43 experts from 16 European countries and 8 European organizations. A working group drafted a proposal, which was revised in several rounds of internal and external review by a multidisciplinary group of experts. RESULT: The quality criteria address the provision of information, communication and informed consent, predictive ability and utility of the test, and quality assurance. CONCLUSION: The consensus agreement on the quality of health checks aim to enhance informed decision making in clients and protects the affordability of the health care system. The criteria can be developed further into a formal standard and regulation if such authority is warranted. PMID- 25117527 TI - Distinct associations of different sedentary behaviors with health-related attributes among older adults. AB - OBJECTIVE: Leisure-time sedentary behaviors (LTSBs) have been associated adversely with health outcomes. However, limited research has focused on different categories of LTSB. We aimed at identifying categories of LTSBs and examining their separate associations with indices of health among Japanese older adults. METHODS: A postal survey collected data on self-reported health, psychological distress, body mass index, moderate-to-vigorous physical activity (MVPA), LTSBs (five behaviors) and socio-demographic characteristics from 1,580 Japanese older adults (67% response rate; 65-74 years) in 2010. Exploratory factor analysis was used to classify LTSBs. Odds ratios (ORs) were calculated for associations of LTSB categories with self-reported health, psychological distress, overweight, and lower MVPA. Data were analyzed in 2013. RESULTS: Two categories of LTSB: passive sedentary time (consisting of TV time, listening or talking while sitting, and sitting around) and mentally-active sedentary time (consisting of computer-use and reading books or newspapers) were identified. Higher passive sedentary time was associated with a higher odds of being overweight (OR: 1.39, [95% CI: 1.08-1.80]), and lower MVPA (1.26, [1.02-1.54]). Higher mentally-active sedentary time was associated with lower odds of lower MVPA (0.70, [0.57-0.86]). CONCLUSIONS: Two types of sedentary time-passive and mentally-active-may play different roles in older adults' well-being. PMID- 25117529 TI - Sesamin suppresses macrophage-derived chemokine expression in human monocytes via epigenetic regulation. AB - BACKGROUND: Chemokines play important roles in the pathogenesis of asthmatic inflammation. Sesamin, a class of phytoestrogen isolated from sesame seed Sesamum indicum, is recently regarded as an anti-inflammatory agent. However, the effects of sesamin on asthma-related chemokines are unknown. To this end, we investigated the effects of sesamin on the expression interferon-gamma-inducible protein-10 (IP-10/CXCL10), macrophage-derived chemokine (MDC/CCL22), growth-related oncogene alpha (GRO-alpha/CXCL1) and tumor necrosis factor (TNF)-alpha in human monocytes. METHODS: Cells were pretreated with sesamin before lipopolysaccharide (LPS) stimulation. IP-10, MDC, GRO-alpha and TNF-alpha were measured by ELISA. Involved receptors and intracellular signaling were investigated by receptor antagonists, pathway inhibitors, western blotting and chromatin immunoprecipitation. RESULTS: Sesamin suppressed LPS-induced MDC in THP-1 and human primary monocytes. Sesamin suppressed LPS-induced IP-10 in THP-1 cells, but not human primary monocytes. Sesamin had no effects on LPS-induced GRO-alpha and TNF-alpha expression in THP-1 and human primary monocytes. The suppressive effect of sesamin on MDC was reversed by the estrogen receptor (ER) and peroxisomal proliferator-activated receptor (PPAR)-alpha antagonists. Sesamin suppressed LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK)-p38 and nuclear factor kappa B (NFkappaB)-p65. Sesamin suppressed histone H3/H4 acetylation in the MDC promoter region. CONCLUSION: Sesamin suppressed LPS-induced MDC expression via the ER, the PPAR-alpha, the MAPK-p38 pathway, the NFkappaB-p65 pathway and the epigenetic regulation. Sesamin may have therapeutic potential in preventing and treating asthma. PMID- 25117530 TI - Dynamically optimizing experiment schedules of a laboratory robot system with simulated annealing. AB - A scheduler has been developed for an integrated laboratory robot system that operates in an always-on mode. The integrated system is designed for imaging plates containing protein crystallization experiments, and it allows crystallographers to enter plates at any time and request that they be imaged at multiple time points in the future. The scheduler must rearrange tasks within the time it takes to image one plate, trading off the quality of the schedule for the speed of the computation. For this reason, the scheduler was based on a simulated annealing algorithm with an objective function that makes use of a linear programming solver. To optimize the scheduler, extensive computational simulations were performed involving a difficult but representative scheduling problem. The simulations explore multiple configurations of the simulated annealing algorithm, including both geometric and adaptive annealing schedules, 3 neighborhood functions, and 20 neighborhood diameters. An optimal configuration was found that produced the best results in less than 60 seconds, well within the window necessary to dynamically reschedule imaging tasks as new plates are entered into the system. PMID- 25117532 TI - The ecology of yeasts in the bark beetle holobiont: a century of research revisited. AB - Yeasts are extremely common associates of scolytine bark beetles, yet the basic ecology of yeasts in the bark beetle holobiont remains poorly understood. Yeasts are present in all beetle life stages and consistently isolated from adult, larval, and pupal integuments and mycangial structures, but yeasts are also found in oviposition galleries, pupal chambers, larval and adult digestive tracts, as well as phloem and xylem tissues. Yeasts in the Saccharomycetaceae family are the most prevalent associates, and most individual beetles are associated with only one or several yeast species. Kuraishia capsulata and Ogataea pini are the most commonly encountered yeast species in surveys of Dendroctonus and Ips beetles; most beetles that have been surveyed are vectors for one or both yeasts. Yeasts have significant but often overlooked functional roles in bark beetle ecology. Infochemicals resulting from volatile production by yeast have wide-ranging bioactivity for arthropods: Yeast emissions attract beetles at low concentrations but repel beetles at high concentrations, and yeast emissions can also serve as cues to predators and parasites of bark beetles. In some cases, yeasts can modify tree chemistry over time or metabolize toxic terpenoids, though potential consequences for beetle performance or the growth of nutritional fungi remain to be demonstrated. Also, the presence of yeast species can restrict or promote the establishment and growth of filamentous fungi, including mutualists, entomopathogens, and opportunistic saprophytes. The role of yeasts as nutritional symbionts has received mixed support, though a nutritional hypothesis has not been extensively tested. Continued research on the functional ecology of bark beetle-yeast associations is needed to better understand the emergent properties of these complex symbiont assemblages. PMID- 25117533 TI - Label-free colorimetric detection of cadmium ions in rice samples using gold nanoparticles. AB - A simple and label-free colorimetric method for cadmium ions (Cd(2+)) detection using unmodified gold nanoparticles (AuNPs) is reported. The unmodified AuNPs easily aggregate in a high concentration of NaCl solution, but the presence of glutathione (GSH) can prevent the salt-induced aggregation of AuNPs. When Cd(2+) is added to the stable mixture of AuNPs, GSH, and NaCl, Cd(2+) can coordinate with 4* GSH as a spherical shaped complex, which decreases the amount of free GSH on the surface of gold nanoparticles to weaken the stability of AuNPs, and AuNPs will easily aggregate in high-salt conditions. On the basis of the mechanism, we design a simple, label-free colorimetric method using AuNPs accompanied by GSH in a high-salt environment to detect Cd(2+) in water and digested rice samples. PMID- 25117531 TI - Endophytic fungi: expanding the arsenal of industrial enzyme producers. AB - Endophytic fungi, mostly belonging to the Ascomycota, are found in the intercellular spaces of the aerial plant parts, particularly in leaf sheaths, sometimes even within the bark and root system without inducing any visual symptoms of their presence. These fungi appear to have a capacity to produce a wide range of enzymes and secondary metabolites exhibiting a variety of biological activities. However, they have been only barely exploited as sources of enzymes of industrial interest. This review emphasizes the suitability and possible advantages of including the endophytic fungi in the screening of new enzyme producing organisms as well as in studies aiming to optimize the production of enzymes through well-known culture processes. Apparently endophytic fungi possess the two types of extracellular enzymatic systems necessary to degrade the vegetal biomass: (1) the hydrolytic system responsible for polysaccharide degradation consisting mainly in xylanases and cellulases; and (2) the unique oxidative ligninolytic system, which degrades lignin and opens phenyl rings, comprises mainly laccases, ligninases and peroxidases. The obvious ability of endophytic fungi to degrade the complex structure of lignocellulose makes them useful in the exploration of the lignocellulosic biomass for the production of fuel ethanol and other value-added commodity chemicals. In addition to this, endophytic fungi may become new sources of industrially useful enzymes such as lipases, amylases and proteases. PMID- 25117535 TI - The energy allocation function of sleep: a unifying theory of sleep, torpor, and continuous wakefulness. AB - The energy allocation (EA) model defines behavioral strategies that optimize the temporal utilization of energy to maximize reproductive success. This model proposes that all species of the animal kingdom share a universal sleep function that shunts waking energy utilization toward sleep-dependent biological investment. For endotherms, REM sleep evolved to enhance energy appropriation for somatic and CNS-related processes by eliminating thermoregulatory defenses and skeletal muscle tone. Alternating REM with NREM sleep conserves energy by decreasing the need for core body temperature defense. Three EA phenotypes are proposed: sleep-wake cycling, torpor, and continuous (or predominant) wakefulness. Each phenotype carries inherent costs and benefits. Sleep-wake cycling downregulates specific biological processes in waking and upregulates them in sleep, thereby decreasing energy demands imposed by wakefulness, reducing cellular infrastructure requirements, and resulting in overall energy conservation. Torpor achieves the greatest energy savings, but critical biological operations are compromised. Continuous wakefulness maximizes niche exploitation, but endures the greatest energy demands. The EA model advances a new construct for understanding sleep-wake organization in ontogenetic and phylogenetic domains. PMID- 25117534 TI - Detection of Kaposi's sarcoma associated herpesvirus nucleic acids using a smartphone accessory. AB - Kaposi's sarcoma (KS) is an infectious cancer occurring in immune-compromised patients, caused by Kaposi's sarcoma associated herpesvirus (KSHV). Our vision is to simplify the process of KS diagnosis through the creation of a smartphone based point-of-care system capable of yielding an actionable diagnostic readout starting from a raw biopsy sample. In this work we develop the sensing mechanism for the overall system, a smartphone accessory capable of detecting KSHV nucleic acids. The accessory reads out microfluidic chips filled with a colorimetric nanoparticle assay targeted at KSHV. We calculate that our final device can read out gold nanoparticle solutions with an accuracy of 0.05 OD, and we demonstrate that it can detect DNA sequences from KSHV down to 1 nM. We believe that through integration with our previously developed components, a smartphone based system like the one studied here can provide accurate detection information, as well as a simple platform for field based clinical diagnosis and research. PMID- 25117536 TI - Soft perforation of cardiolipin-containing planar lipid bilayer membrane by cytochrome c and H(2)O(2). AB - The release of cytochrome c (cyt c) from mitochondria is responsible for initiation of cell apoptosis. Although extramitochondrial proteins are thought to initiate this release, the exact mechanism remains unclear. Cyt c binds to and penetrates lipid bilayer membranes of specific phospholipid cardiolipin (CL) contained in mitochondria. We present here the experimental results of monitoring planar BLM (pBLM) from mixtures of azolectin and of CL (4/1 by moles) by triangle voltage pulses of 100 mV in amplitude and frequency of 2 Hz. The BLM were modified by a successive addition of cyt c and of H(2)O(2) in water solution. It is shown that the addition of cyt c alone leads to a stepwise increase in the ionic conductance of the pBLM, indicating the appearance of transmembrane pores. Pore lifetimes then reached several seconds at an average pore diameter of ~2 nm. Current-voltage characteristics were then linear and passed through the origin which is characteristic for broad, nonselective ion pores. Subsequent addition of H(2)O(2) caused a dramatic increase in transmembrane current at retention of average pore size constant. Observed increase in membrane current is due to growth of a number of pores in an open state. We suggest that hydrogen peroxide in the presence of cyt c promotes a peroxidation of membrane phospholipids to form lysolipids, the embedding of which stabilizes the edge of the pore and the surface of lipid bilayer. PMID- 25117539 TI - First report of a direct surface plasmon resonance immunosensor for a small molecule seafood toxin. AB - Tetrodotoxin (TTX), a small molecular weight neurotoxin, is responsible for poisoning events that traditionally occur from consumption of contaminated puffer fish. Recent studies have shown a growing number of foods contaminated with TTX and a larger number of waters and associated countries where the toxin may occur. The apparent expanding prevalence of TTX supports a growing need for screening assays that can be used to detect potentially harmful food. In the past few years, surface plasmon resonance (SPR) biosensors have been developed for rapid, robust detection of TTX; however, these assays focus on detection of unbound antibody from an inhibition reaction with the toxin. This manuscript introduces the first direct immunoassay for a seafood toxin, specifically TTX. Major advantages of this assay compared to indirect assays include increased speed of analysis, decreased use of biological reagents, and improved confidence in the detection of the toxin, along with the ability to characterize the antibody/toxin interaction. The analytical method introduced in this paper could be applied to other seafood toxins, as well as to a wide range of low molecular weight targets. PMID- 25117538 TI - Getting Black Men to Undergo Prostate Cancer Screening: The Role of Social Capital. AB - Despite higher rates of prostate cancer-related mortality and later stage of prostate cancer diagnosis, Black/African American men are significantly less likely than non-Hispanic White men to use early detection screening tools, like prostate-specific antigen (PSA) testing for prostate cancer. Lower screening rates may be due, in part, to controversy over the value of prostate cancer screenings as part of routine preventive care for men, but Black men represent a high-risk group for prostate cancer that may still benefit from PSA testing. Exploring the role of social factors that might be associated with PSA testing can increase knowledge of what might promote screening behaviors for prostate cancer and other health conditions for which Black men are at high risk. Using multilevel logistic regression, this study analyzed self-report lifetime use of PSA test for 829 Black men older than 45 years across 381 Philadelphia census tracts. This study included individual demographic and aggregated social capital data from the Public Health Management Corporation's 2004, 2006, and 2008 waves of the Community Health Database, and sociodemographic characteristics from the 2000 U.S. Census. Each unit increase in community participation was associated with a 3 to 3.5 times greater likelihood of having had a PSA test (odds ratio = 3.35). Findings suggest that structural forms of social capital may play a role in screening behaviors for Black men in Philadelphia. A better understanding of the mechanism underlying the link between social capital and screening behaviors can inform how researchers and interventionists develop tools to promote screening for those who need it. PMID- 25117537 TI - Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection. AB - The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections. PMID- 25117543 TI - An integrative computational model for large-scale identification of metalloproteins in microbial genomes: a focus on iron-sulfur cluster proteins. AB - Metalloproteins represent a ubiquitous group of molecules which are crucial to the survival of all living organisms. While several metal-binding motifs have been defined, it remains challenging to confidently identify metalloproteins from primary protein sequences using computational approaches alone. Here, we describe a comprehensive strategy based on a machine learning approach to design and assess a penalized generalized linear model. We used this strategy to detect members of the iron-sulfur cluster protein family. A new category of descriptors, whose profile is based on profile hidden Markov models, encoding structural information was combined with public descriptors into a linear model. The model was trained and tested on distinct datasets composed of well-characterized iron sulfur protein sequences, and the resulting model provided higher sensitivity compared to a motif-based approach, while maintaining a good level of specificity. Analysis of this linear model allows us to detect and quantify the contribution of each descriptor, providing us with a better understanding of this complex protein family along with valuable indications for further experimental characterization. Two newly-identified proteins, YhcC and YdiJ, were functionally validated as genuine iron-sulfur proteins, confirming the prediction. The computational model was then applied to over 550 prokaryotic genomes to screen for iron-sulfur proteomes; the results are publicly available at: . This study represents a proof-of-concept for the application of a penalized linear model to identify metalloprotein superfamilies on a large-scale. The application employed here, screening for iron-sulfur proteomes, provides new candidates for further biochemical and structural analysis as well as new resources for an extensive exploration of iron-sulfuromes in the microbial world. PMID- 25117541 TI - Human premotor areas parse sequences into their spatial and temporal features. AB - Skilled performance is characterized by precise and flexible control of movement sequences in space and time. Recent theories suggest that integrated spatio temporal trajectories are generated by intrinsic dynamics of motor and premotor networks. This contrasts with behavioural advantages that emerge when a trained spatial or temporal feature of sequences is transferred to a new spatio-temporal combination arguing for independent neural representations of these sequence features. We used a new fMRI pattern classification approach to identify brain regions with independent vs integrated representations. A distinct regional dissociation within motor areas was revealed: whereas only the contralateral primary motor cortex exhibited unique patterns for each spatio-temporal sequence combination, bilateral premotor areas represented spatial and temporal features independently of each other. These findings advocate a unique function of higher motor areas for flexible recombination and efficient encoding of complex motor behaviours. PMID- 25117540 TI - The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes. AB - The mechanisms generating epileptic neuronal networks following insults such as severe seizures are unknown. We have previously shown that interfering with the function of the neuron-restrictive silencer factor (NRSF/REST), an important transcription factor that influences neuronal phenotype, attenuated development of this disorder. In this study, we found that epilepsy-provoking seizures increased the low NRSF levels in mature hippocampus several fold yet surprisingly, provoked repression of only a subset (~10%) of potential NRSF target genes. Accordingly, the repressed gene-set was rescued when NRSF binding to chromatin was blocked. Unexpectedly, genes selectively repressed by NRSF had mid-range binding frequencies to the repressor, a property that rendered them sensitive to moderate fluctuations of NRSF levels. Genes selectively regulated by NRSF during epileptogenesis coded for ion channels, receptors, and other crucial contributors to neuronal function. Thus, dynamic, selective regulation of NRSF target genes may play a role in influencing neuronal properties in pathological and physiological contexts. PMID- 25117544 TI - Attention and working memory in elderly: the influence of a distracting environment. AB - The present work investigated the effect of a distracting environment in the performance of attentional and working memory (WM) tasks in elderly participants. To this end, forty elderly performed two attentional tasks (simple reaction time and go/no-go tasks), and three WM tasks (arithmetic, memory for digits and sequences of letters and numbers). Each participant performed the tasks in a distracting and a non-distracting environment, with an interval of 14-21 days between sessions. The results revealed better performance in the attentional tasks when these were done in the non-distracting environment, as compared to when they were done in the distracting environment. Specifically, participants provided more accurate responses, fewer false alarms and omissions when responding in the non-distracting environment than when responding in the distracting environment. Participants were also faster at providing correct responses in the go/no-go task when it was performed in the non-distracting environment. As for the memory tasks, the effect of type of environment was significant only in the memory for digits in a forward direction task. Our data suggest the need to consider the potential damaging consequences of distracting environments when the elderly have to perform tasks that demand their attention. Specific examples of such situations are presented in the discussion (e.g., distracting effect of environment on medical and on psychological evaluations). PMID- 25117542 TI - Subacute manganese exposure in rats is a neurochemical model of early manganese toxicity. AB - Manganese (Mn) is an essential trace element, but excess exposure leads to accumulation in biological tissues, including the brain. Chronically high Mn levels in the brain are neurotoxic and can result in a progressive, irreversible neurological disorder known as manganism. Manganism has signs and symptoms similar to, but distinguishable from idiopathic Parkinson's disease, which include both psychological and motor disturbances. Evidence suggests that Mn exposure impacts neurotransmitter levels in the brain. However, it remains unclear if subacute, low-level Mn exposure resulted in alterations in neurotransmitter systems with concomitant behavioral deficits. The current study used high performance liquid chromatography to quantify neurotransmitter levels in rat striatum (STR), substantia nigra (SN), and hippocampus (HP). Subacute Mn exposure via i.p. injection of 15mg Mn/kg as MnCl2 caused significantly increased dopamine (DA) levels in the STR. The enhancement was accompanied by significantly elevated levels of the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the STR. In addition, levels of HVA were significantly increased in the SN and HP. These data indicate that subacute, low level Mn exposure disrupts multiple neurotransmitter systems in the rat brain which may be responsible, in part, for observed locomotor deficits. PMID- 25117545 TI - fadD deletion and fadL overexpression in Escherichia coli increase hydroxy long chain fatty acid productivity. AB - A major problem of long-chain fatty acid (LCFA) hydroxylation using Escherichia coli is that FadD (long-chain fatty acyl-CoA synthetase), which is necessary for exogenous LCFA transport, also initiates cellular consumption of LCFA. In this study, an effective method to prevent the cellular consumption of LCFA without impairing its transport is proposed. The main idea is that a heterologous enzyme which consumes LCFA can replace FadD in LCFA transport. For the model heterologous enzyme, CYP153A from Marinobacter aquaeolei, which converts palmitic acid into omega-hydroxy palmitic acid, was expressed in E. coli. When fadD was deleted from an E. coli strain, CYP153A indeed maintained the ability to transport LCFA. A disadvantage of fadD deletion mutant is the fact that FadD deficiency downregulates the transcription of fadL (outer membrane LCFA transporter) via FadR (fatty acid metabolism regulator protein), was solved by fadL overexpression from a plasmid. In addition, the overexpression of fadL was able to offset catabolite repression on fadL, allowing glucose to be used as the primary carbon source. In conclusion, the strain with fadD deletion and fadL overexpression showed 5.5-fold increase in productivity compared to the wild-type strain, converting 2.6 g/L (10.0 mM) of palmitic acid into 2.4 g/L (8.8 mM) of omega-hydroxy palmitic acid in a shake flask. This simple genetic manipulation can be applied to any LCFA hydroxylation using E. coli. PMID- 25117546 TI - Facile synthesis of oxidic PEG-modified magnetic polydopamine nanospheres for Candida rugosa lipase immobilization. AB - A versatile method for the design of polydopamine-coated magnetic material with a brush-like structure used for Candida Rugosa lipase (CRL) immobilization was reported in this work. First, polydopamine (PDA) was coated on the surface of Fe3O4 nanospheres (Fe3O4 NPs) with a controllable thickness via dip coating process, and CRL can be immobilized on it directly via covalent bonding. Subsequently, PDA-functionalized Fe3O4 NPs were modified with dialdehyde polyethylene glycol (PEG) to obtain the aldehyde groups, and the brush-like structure of the magnetic supports was formed. After being characterized with various methods, it was verified that the prepared magnetic NPs possessed good monodispersity and displayed high saturation magnetization after modification. Meanwhile, the CRL was immobilized on it covalently, and the enzyme activities such as activity, stability, and reusability were investigated. Significantly, the versatility of polydopamine-inspired chemistry combined with the unique biological nature and tunability with dialdehyde PEG could evoke the efficiency of the CRL, making this a promising coating technique for various bio applications. PMID- 25117547 TI - A recombinant porcine circovirus type 2 expressing the VP1 epitope of the type O foot-and-mouth disease virus is infectious and induce both PCV2 and VP1 epitope antibodies. AB - Porcine circovirus type 2 (PCV2) is the etiological agent of postweaning multisystemic wasting syndrome, a disease that causes huge economic damage in swine industry. A recombinant PCV2 expressing the neutralizing VP1 epitope (aa 141-160) of the foot-and-mouth disease virus (FMDV) was rescued using an infectious cloning technique. The PCV2 antigen and FMDV-VP1 antigenic epitope of the cloned strain recPCV2-CL-VP1 were confirmed by an immunoperoxidase monolayer assay (IPMA) and a capture enzyme-linked immunosorbent assay (ELISA). The morphological features of the recPCV2-CL-VP1 were not discernibly different from those of its parental strain (PCV2-CL). However, the recombinant virus could be differentiated from its parental virus by PCR and capture ELISA. The recPCV2-CL VP1 was demonstrated to replicate stably in PK-15 cells through ten passages. An infection experiment using BALB/c mice showed that both recPCV2-CL-VP1 and PCV2 CL could replicate in the mice, cause various pathological changes, and induce a high level of anti-Cap antibodies. The recombinant virus emulsified with Freund's adjuvant was used to immunize BALB/c mice and induced antibodies against the FMDV VP1 epitope. Hence, the recombinant PCV2 strain, which expressed the neutralizing FMDV-VP1 epitope, provides a valuable platform to develop novel genetic vaccines. PMID- 25117548 TI - Development of droplet digital PCR assays for methanogenic taxa and examination of methanogen communities in full-scale anaerobic digesters. AB - Droplet digital PCR (ddPCR) is a new DNA quantification platform without an external DNA calibrator. This study examined methanogen communities in four full scale anaerobic digesters treating municipal sewage sludge, using ddPCR with taxon-specific primer/TaqMan probe sets (5 orders, 11 families, and 13 genera), many of which were developed in this study. Total methanogen abundance was positively correlated with hydraulic retention time (HRT) and temperature (p < 0.05), though the effect of HRT was stronger (r = 0.864 vs. 0.682, respectively). Moreover, total abundance was strongly correlated with biogas production rate (r = 0.896). HRT was positively correlated with seven methanogenic taxa, while temperature was positively or negatively correlated with 13 taxa (p < 0.05). For instance, the predominant genera Methanosaeta and Methanosarcina were negatively and positively associated, respectively, with temperature only (p < 0.05). Redundancy analysis and principal component analysis using the absolute-abundance dataset indicated that only temperature explained the variability in the methanogen communities at all classification levels. Therefore, HRT was the most important operational factor to influence net methanogen abundance and activity, while temperature governed the composition of the methanogen community. ddPCR enabled absolute quantification of methanogens without the external DNA standards and linked methanogen communities and operational factors, suggesting that it is a promising tool for analyzing the microbial ecology of anaerobic digestion. PMID- 25117549 TI - Evaluation of the prebiotic potential of arabinoxylans from brewer's spent grain. AB - Arabinoxylans (AX) consumption has been related to the treatment and prevention of cardiovascular diseases, type II diabetes, colorectal cancer and obesity. The beneficial health effects are conferred through gut microbiota modulation, and therefore, they have been proposed as potential slowly fermentable prebiotic candidates. As the mechanisms are not yet well understood, the prebiotic potential of AX from brewer's spent grain (BSG) has been investigated. Two types of AX from BSG (AX1 and AX2) of different length and branching averages were fermented with human faecal inocula and compared to fermented cultures containing a commercial prebiotic (fructooligosaccharide (FOS)) and cultures with no added carbohydrate (control). Results demonstrated that the AX were extensively metabolised after 48 h of fermentation. The pH decreased along fermentation and the lowest value was achieved in AX1 cultures. The production of short chain fatty acids (SCFA) was higher in AX cultures than in cultures containing FOS and controls, with AX1 presenting the highest concentrations. The stimulatory effect of beneficial bacteria was higher in AX cultures, and AX2 presented the highest positive effect. Prebiotic potential of AX from BSG was confirmed by the production of SCFA and the modulation of gut microbiota, especially by the high increase in bifidobacteria populations. PMID- 25117550 TI - Polyethylenimine carbon nanotube fiber electrodes for enhanced detection of neurotransmitters. AB - Carbon nanotube (CNT)-based microelectrodes have been investigated as alternatives to carbon-fiber microelectrodes for the detection of neurotransmitters because they are sensitive, exhibit fast electron transfer kinetics, and are more resistant to surface fouling. Wet spinning CNTs into fibers using a coagulating polymer produces a thin, uniform fiber that can be fabricated into an electrode. CNT fibers formed in poly(vinyl alcohol) (PVA) have been used as microelectrodes to detect dopamine, serotonin, and hydrogen peroxide. In this study, we characterize microelectrodes with CNT fibers made in polyethylenimine (PEI), which have much higher conductivity than PVA-CNT fibers. PEI-CNT fibers have lower overpotentials and higher sensitivities than PVA-CNT fiber microelectrodes, with a limit of detection of 5 nM for dopamine. The currents for dopamine were adsorption controlled at PEI-CNT fiber microelectrodes, independent of scan repetition frequency, and stable for over 10 h. PEI-CNT fiber microelectrodes were resistant to surface fouling by serotonin and the metabolite interferant 5-hydroxyindoleacetic acid (5-HIAA). No change in sensitivity was observed for detection of serotonin after 30 flow injection experiments or after 2 h in 5-HIAA for PEI-CNT electrodes. The antifouling properties were maintained in brain slices when serotonin was exogenously applied multiple times or after bathing the slice in 5-HIAA. Thus, PEI-CNT fiber electrodes could be useful for the in vivo monitoring of neurochemicals. PMID- 25117553 TI - Linear and circular dichroism in porphyrin J-aggregates probed by polarization modulated scanning near-field optical microscopy. AB - Polarization modulated scanning near-field optical microscopy (PM-SNOM) is effective in detecting circular and linear dichroism with sub-wavelength resolution. PM-SNOM investigation of the chiroptical properties of single ribbon like nanosized J-aggregates formed by acid induced aggregation of tris-(4 sulfonatophenyl)phenylporphyrin is reported. Linear dichroism maps give evidence of well-organized chromophores packed in linear arrays within the structure of the nanoribbons. Circular dichroism maps indicate that the molecules forming the nanoribbon have an inherently chiral structure at the local scale. PMID- 25117552 TI - Visualization and unsupervised predictive clustering of high-dimensional multimodal neuroimaging data. AB - BACKGROUND: Neuroimaging machine learning studies have largely utilized supervised algorithms - meaning they require both neuroimaging scan data and corresponding target variables (e.g. healthy vs. diseased) to be successfully 'trained' for a prediction task. Noticeably, this approach may not be optimal or possible when the global structure of the data is not well known and the researcher does not have an a priori model to fit the data. NEW METHOD: We set out to investigate the utility of an unsupervised machine learning technique; t distributed stochastic neighbour embedding (t-SNE) in identifying 'unseen' sample population patterns that may exist in high-dimensional neuroimaging data. Multimodal neuroimaging scans from 92 healthy subjects were pre-processed using atlas-based methods, integrated and input into the t-SNE algorithm. Patterns and clusters discovered by the algorithm were visualized using a 2D scatter plot and further analyzed using the K-means clustering algorithm. COMPARISON WITH EXISTING METHODS: t-SNE was evaluated against classical principal component analysis. CONCLUSION: Remarkably, based on unlabelled multimodal scan data, t-SNE separated study subjects into two very distinct clusters which corresponded to subjects' gender labels (cluster silhouette index value=0.79). The resulting clusters were used to develop an unsupervised minimum distance clustering model which identified 93.5% of subjects' gender. Notably, from a neuropsychiatric perspective this method may allow discovery of data-driven disease phenotypes or sub-types of treatment responders. PMID- 25117551 TI - Reference gene selection for quantitative real-time PCR normalization in Reaumuria soongorica. AB - Despite its superiority for evaluating gene expression, real-time quantitative polymerase chain reaction (qPCR) results can be significantly biased by the use of inappropriate reference genes under different experimental conditions. Reaumuria soongorica is a dominant species of desert ecosystems in arid central Asia. Given the increasing interest in ecological engineering and potential genetic resources for arid agronomy, it is important to analyze gene function. However, systematic evaluation of stable reference genes should be performed prior to such analyses. In this study, the stabilities of 10 candidate reference genes were analyzed under 4 kinds of abiotic stresses (drought, salt, dark, and heat) within 4 accessions (HG010, HG020, XGG030, and XGG040) from 2 different habitats using 3 algorithms (geNorm, NormFinder, and BestKeeper). After validation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large unite (rbcL) expression pattern, our data suggested that histone H2A (H2A) and eukaryotic initiation factor 4A-2 (EIF4A2) were the most stable reference genes, cyclophilin (CYCL) was moderate, and elongation factor 1alpha (EF1alpha) was the worst choice. This first systematic analysis for stably expressed genes will facilitate future functional analyses and deep mining of genetic resources in R. soongorica and other species of the Reaumuria genus. PMID- 25117554 TI - Linear signal hyperintensity adjacent to the subchondral bone plate at the knee on T2-weighted fat-saturated sequences: imaging aspects and association with structural lesions. AB - OBJECTIVE: To describe the association between linear T2 signal abnormalities in the subchondral bone and structural knee lesions. MATERIALS AND METHODS: MR studies of patients referred for the evaluation of knee pain were retrospectively evaluated and 133 of these patients presented bone marrow edema pattern (BMEP) (study group) and while 61 did not (control group). The presence of linear anomalies of the subchondral bone on T2-weighted fat-saturated sequences was evaluated. The findings were correlated to the presence of structural knee lesions and to the duration of the patient's symptoms. Histologic analysis of a cadaveric specimen was used for anatomic correlation. RESULTS: Linear T2 hyperintensities at the subchondral bone were present in 41% of patients with BMEP. None of the patients in the control group presented this sign. When a subchondral linear hyperintensity was present, the prevalence of radial or root tears was high and that of horizontal tears was low (71.4 and 4.8%, respectively). Sixty-nine percent of the patients with a subchondral insufficiency fracture presented a subchondral linear hyperintensity. It was significantly more prevalent in patients with acute or sub-acute symptoms (p < 0.0001). CONCLUSIONS: The studied linear T2 hyperintensity is located at the subchondral spongiosa and can be secondary to local or distant joint injuries. Its presence should evoke acute and sub-acute knee injuries. This sign is closely related to subchondral insufficiency fractures and meniscal tears with a compromise in meniscal function. PMID- 25117555 TI - The scapular glenopolar angle: standard values and side differences. AB - OBJECTIVE: The aim of this study is to determine normal glenopolar angle (GPA) values on bone specimens of the scapula and compare them with various radiological views and CT examination. MATERIALS AND METHODS: GPA values were measured on 100 mature, dry, non-paired scapulae, 20 pairs of dry scapulae, 50 AP radiographs of the shoulder, 50 Neer I views, 50 AP chest radiographs and 20 3D CT reconstructions of the scapula. RESULTS: Measurements made on bone specimens of the scapula showed an average GPA value of 42.3 degrees ; the mean absolute side-to-side difference was on average 1.6 degrees . The average GPA measured on 50 AP shoulder radiographs was 35.9 degrees , on Neer I views 40.6 degrees and AP chest radiographs 37.1 degrees , with the mean absolute side-to-side difference on average 4.9 degrees ; on 3D CT the average GPA was 43.0 degrees and the mean absolute side-to-side difference on average 1.4 degrees . CONCLUSION: GPA values depend on the method of measurement used. Measurements made on 3D CT reconstructions and Neer I views showed almost the same values as those measured on bone specimens. The values measured on AP shoulder views and AP chest radiographs were statistically significantly lower. Side-to-side variability (right and left) measured on 3D CT reconstructions was insignificant, and the obtained values corresponded to the values from bone specimens. Therefore, the best method to measure the GPA is a 3D CT reconstruction and an exact Neer I projection. PMID- 25117557 TI - Health-related quality of life among online university students. AB - BACKGROUND AND OBJECTIVES: Online university students are a growing population whose health has received minimal attention. The purpose of this cross-sectional Internet survey was to identify risk factors for the health status among online university students. METHODS: This online survey collected data from 301 online university students through a large, US-based participant pool and LinkedIn. Health status was measured using 3 elements of health-related quality of life (HRQOL): self-rated overall health (SRH), unhealthy days, and recent activity limitation days. All 3 measures were dichotomized. RESULTS: The odds of poor SRH were higher for people who reported a body mass index in the overweight and obese categories (odds ratio [OR] = 2.99, P < .05) and for those who reported being smokers (OR = 2.52, P = .03). The odds of frequent unhealthy days were lower for those who made more than $35 000 compared with those who reported making less (OR = 0.50, P = .03) and those who exercised 4 or more times a week compared with those who exercised less (OR = 0.28, P < .05). The odds of frequent activity limitation were lower for those who reported an income of more than $35 000 (OR = 0.29, P = .04) and higher for persons who reported belonging to "other" race (OR = 14.75, P = .00). CONCLUSIONS: Universities might fruitfully target health promotion programs for online students who are low income, in disadvantaged racial groups, who are overweight, smoke, and who do not exercise. PMID- 25117558 TI - The limits of traditional approaches to informed consent for genomic medicine. AB - This paper argues that it will be important for new genomic technologies to recognize the limits of traditional approaches to informed consent, so that other regarding implications of genomic information can be properly contextualized and individual rights respected. Respect for individual autonomy will increasingly require dynamic consideration of the interrelated dimensions of individual and broader community interests, so that the interests of one do not undermine fundamental interests of the other. In this, protection of individual rights will be a complex interplay between individual and community concerns. PMID- 25117559 TI - Engineering bacterial microcompartment shells: chimeric shell proteins and chimeric carboxysome shells. AB - Bacterial microcompartments (BMCs) are self-assembling organelles composed entirely of protein. Depending on the enzymes they encapsulate, BMCs function in either inorganic carbon fixation (carboxysomes) or organic carbon utilization (metabolosomes). The hallmark feature of all BMCs is a selectively permeable shell formed by multiple paralogous proteins, each proposed to confer specific flux characteristics. Gene clusters encoding diverse BMCs are distributed broadly across bacterial phyla, providing a rich variety of building blocks with a predicted range of permeability properties. In theory, shell permeability can be engineered by modifying residues flanking the pores (symmetry axes) of hexameric shell proteins or by combining shell proteins from different types of BMCs into chimeric shells. We undertook both approaches to altering shell properties using the carboxysome as a model system. There are two types of carboxysomes, alpha and beta. In both, the predominant shell protein(s) contain a single copy of the BMC domain (pfam00936), but they are significantly different in primary structure. Indeed, phylogenetic analysis shows that the two types of carboxysome shell proteins are more similar to their counterparts in metabolosomes than to each other. We solved high resolution crystal structures of the major shell proteins, CsoS1 and CcmK2, and the presumed minor shell protein CcmK4, representing both types of cyanobacterial carboxysomes and then tested the interchangeability. The in vivo study presented here confirms that both engineering pores to mimic those of other shell proteins and the construction of chimeric shells is feasible. PMID- 25117556 TI - Profiles of Risk Among HIV-Infected Youth in Clinic Settings. AB - Despite the rising number of new HIV infections among youth, few tailored interventions for youth living with HIV (YLH) have been developed and rigorously tested. Developing tailored interventions necessitates identifying different profiles of YLH and understanding how risk and protective factors cluster together. Obtaining this critical information requires accessing a sufficiently large sample of YLH from diverse geographic settings such as those available through the Adolescent Trials Network for HIV Interventions (ATN). We recruited a cross-sectional sample of 1,712 YLH from ATN clinics; participants completed a survey on psychosocial and health factors. Using latent class analysis on nine composite variables representing risk factors, we identified five classes distinguished by substance use, sexual behavior, and pregnancy history and differing on health outcomes. Findings suggest a need for tailored interventions addressing multiple risky behaviors of HIV-infected youth and research to clarify how intervention effectiveness may differ by risk profile. PMID- 25117560 TI - Nitrogen-enriched, double-shelled carbon/layered double hydroxide hollow microspheres for excellent electrochemical performance. AB - A unique, double-shelled, hollow, carbon-based composite with enriched nitrogen has been prepared through a facile and versatile synthetic strategy. The hierarchical composite employs the nitrogen-enriched carbon hollow sphere as an interior shell and intercrossed Ni/Al layered double hydroxide (LDH) nanosheets as an exterior shell. The obtained N-C@LDH hollow microspheres (HMS) have high nitrogen enrichment, large specific surface area (337 m(2) g(-1)), and uniform and open mesoporous structure. Taking advantage of these characteristics, the composite exhibits obviously superior capacitive behavior, including high specific capacitance, excellent rate capability and good cycling stability, compared with nitrogen-free carbon@LDH composite and hollow LDH without carbon shell. The composite displays high specific capacitance of 1711.51 F g(-1) at a current density of 1 A g(-1). In particular, the high specific capacitance can be kept to 997.3 F g(-1) at a high current density of 10 A g(-1), which still retains 94.97% of the initial specific capacitance after 500 cycles at this high current density. This N-enriched, hollow carbon/LDH composite can be expected to be a promising electrode material for electrochemical capacitors due to its high electrochemical performance. PMID- 25117561 TI - MDCT diagnosis of gastroduodenal ulcers: key imaging features with endoscopic correlation. AB - Although the overall prevalence of peptic ulcer disease (PUD) and related hospitalizations are decreasing, the initial presentation of complicated PUD on CT remains common. It, therefore, remains critical for radiologists to recognize the findings of PUD at CT for initial diagnosis. While the CT findings of complicated PUD have been previously described in the literature, the CT findings of uncomplicated PUD have not been well documented. Furthermore, although CT is certainly not the diagnostic evaluation of choice for patients with suspected uncomplicated PUD, many patients with PUD will nonetheless present to the emergency department with unexplained abdominal pain and undergo MDCT evaluation as the initial diagnostic test. Therefore, recognizing the MDCT findings of uncomplicated PUD can help appropriately direct patient management, and help prevent the development of complications. To facilitate improved recognition of PUD on abdominal CT, we present an overview of the CT findings of both uncomplicated and complicated PUD, as well as several diagnostic pitfalls which can result in misdiagnosis from peptic ulcer mimics. PMID- 25117562 TI - Diffusion-weighted imaging of the liver: comparison of image quality between monopolar and bipolar acquisition schemes at 3T. AB - PURPOSE: To compare image quality of monopolar and bipolar diffusion-weighted imaging (DWI) sequences of the liver at 3T. METHODS: 32 healthy volunteers (mean 27 +/- 8 years; 27 M/5F) and 11 patients (mean age 58 +/- 14 years; 8 M/3F) underwent liver MRI using a 3T system incorporating 2-channel parallel transmission for B1-shimming and reduced B1-inhomogeneity. Scans included free breathing DWI sequences (b-value 0, 400, 800 s/mm(2)) acquired using both monopolar and bipolar techniques. Estimated signal-to-noise ratio (eSNR), apparent diffusion coefficient (ADC), and measures of subjective image quality on b-800 images, scored on a 1-5 scale by two independent radiologists, were compared between sequences. RESULTS: Monopolar sequence demonstrated significantly higher eSNR (volunteers: 12.7 +/- 4.0 vs. 11.3 +/- 3.5, patients: 11.4 +/- 4.0 vs. 10.2 +/- 3.3; p <= 0.013) compared with the bipolar sequence. Monopolar sequence also achieved significantly higher scores for reader 1 in volunteers and patients in terms of clarity of right lobe edge, clarity of intra hepatic vessels, conspicuity of the left lobe, and overall diagnostic quality (p <= 0.031), as well as significantly higher scores for reader 2 in volunteers in terms of clarity of intra-hepatic vessels, conspicuity of the left lobe, and overall diagnostic quality (p <= 0.035). Respiratory motion artifact was not significantly different between sequences in patients or volunteers for either reader (p >= 0.191). Hepatic ADC was significantly lower using monopolar technique only in volunteers (1.28 +/- 0.12 vs. 1.43 +/- 0.15, p < 0.001). CONCLUSION: In comparison with past studies performed at 1.5T, when using a modern 3T system, we observed improved image quality of liver DWI using a monopolar, rather than a bipolar, acquisition scheme, largely attributed to higher eSNR. PMID- 25117563 TI - Multimodality imaging of penile cancer: what radiologists need to know. AB - The purpose of this article is to provide a comprehensive update on the role of imaging in the diagnosis and management of penile cancer. Imaging plays a major role in the initial assessment, treatment planning, and follow-up of patients with penile carcinoma. MRI helps in assessing the T staging of the primary and in detecting local recurrence. PET/CT and CT are useful for detecting regional nodal and distant metastases. PMID- 25117564 TI - Maternal smoking during pregnancy and adverse outcomes in offspring: genetic and environmental sources of covariance. AB - Maternal smoking during pregnancy (SDP) has been associated with several psychiatric outcomes in the offspring; studies have questioned whether the associations are causal, however. We analyzed all children born in Sweden between 1983 and 2009 to investigate the effect of SDP on multiple indicators of adverse outcomes in three areas: pregnancy outcomes (birth weight, preterm birth and being born small for gestational age), long-term cognitive abilities (low academic achievement and general cognitive ability) and externalizing behaviors (criminal conviction, violent criminal conviction and drug misuse). SDP was associated with all outcomes. Within-family analyses of the pregnancy outcomes were consistent with a causal interpretation as the associations persisted when siblings discordant for SDP were compared. For the cognitive and externalizing outcomes, the results were not consistent with causal effects; when comparing differentially exposed siblings none of the associations remained significant. In quantitative genetic models genetic factors explained the majority of the associations between SDP and cognitive and externalizing outcomes. The results suggest that the associations between SDP in mothers and cognition and externalizing behaviors in their offspring is primarily due to genetic effects that influence the behaviors in both generations. PMID- 25117566 TI - Secretoglobin 3A2 attenuates lipopolysaccharide-induced inflammation through inhibition of ERK and JNK pathways in bronchial epithelial cells. AB - Secretoglobin (SCGB) 3A2, previously known as uteroglobin-related protein 1, is a secreted protein highly expressed in the epithelial cells of the airways. It has been demonstrated that SCGB3A2 is involved in allergic airway inflammation such as bronchial asthma. However, the role of SCGB3A2 in lipopolysaccharide (LPS) induced airway inflammation has yet to be reported. The goal of this study was therefore to clarify the role of SCGB3A2 in LPS-induced airway inflammation. We stimulated BEAS-2B, human bronchial epithelial cells, with LPS and analyzed messenger RNA (mRNA) expression of tumor necrosis factor (TNF)-alpha and CXCL8 with or without pre-incubation of SCGB3A2. The mRNA expression of TNF-alpha and CXCL8 was clearly upregulated 3 h after LPS stimulation, and pre-incubation of SCGB3A2 significantly inhibited the upregulation of the mRNA expression. The pre incubation of SCGB3A2 also inhibited LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase in BEAS-2B cells. Furthermore, PD98059, a specific inhibitor for ERK, as well as SP600125, a specific inhibitor for JNK, inhibited LPS-induced mRNA upregulation of inflammatory mediators. These results demonstrate the novel biological activity of SCGB3A2, which is that it attenuates LPS-induced inflammation in bronchial epithelial cells through inhibition of ERK and JNK activation. PMID- 25117565 TI - Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure. AB - The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins) and 823 phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a >= 2-fold alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure. PMID- 25117567 TI - Naringin attenuates the development of carrageenan-induced acute lung inflammation through inhibition of NF-kappab, STAT3 and pro-inflammatory mediators and enhancement of IkappaBalpha and anti-inflammatory cytokines. AB - Naringin has been reported to possess diverse pharmacological properties, including anti-arthritic and anti-inflammatory activities. The aim of the present study was to determine the potential anti-inflammatory effect of naringin in a mouse model of carrageenan-induced pleurisy. A single dose of naringin (40 and 80 mg/kg) was administered per oral (p.o.) 1 h before carrageenan (Cg) administration. Pro- and anti-inflammatory cytokines were analysed in pleural fluid. We also assessed the effects of naringin on the expression levels of iNOS, inducible cyclooxygenase isoform (COX-2), ICAM-1, MIP-2, PGE2, STAT3, TGF-beta1, nuclear factor kappa B (NF-kappaB) and inhibitor of kappa B (IkappaBalpha) in lung tissue. The histological examinations revealed anti-inflammatory effect of naringin while Cg group deteriorated. Naringin downregulated Th1 and upregulated Th2 cytokines. Western blot analyses revealed increased protein expression of NF kappaB, STAT3 and COX-2 and decreased IkappaBalpha in response to Cg treatment, which were reversed by the treatment with naringin. In the Cg group, mRNA expression levels of pro-inflammatory mediators upregulated and anti-inflammatory mediators downregulated. Naringin reversed these actions. PMID- 25117568 TI - Silymarin attenuates airway inflammation induced by cigarette smoke in mice. AB - Cigarette smoke (CS), which increases inflammation and oxidative stress, is a major risk factor for the development of COPD. In this study, we investigated the effects of silymarin, a polyphenolic flavonoid isolated from the seeds and fruits of milk thistle, on CS-induced airway inflammation and oxidative stress in mice and the possible mechanisms. BALB/c mice were exposed to CS for 2 h twice daily, 6 days per week for 4 weeks. Silymarin (25, 50 mg/kg.day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell counting and the detection of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination, myeloperoxidase (MPO) activity assay, superoxide dismutase (SOD) activities, and malondialdehyde (MDA) levels. The phosphorylation of ERK and p38 was evaluated by Western blotting. Pretreatment with silymarin significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, and lumen obstruction. The numbers of total cells, macrophages, and neutrophils, along with the MPO activity (a marker of neutrophil accumulation) in BALF, were remarkably decreased by silymarin in CS-exposed mice (all p<0.05). In addition, silymarin pretreatment dampened the secretion of TNF-alpha, IL-1beta, and IL-8 in BALF. High-dose silymarin (50 mg/kg.day) administration also prevented CS-induced elevation in MDA levels and decrease in SOD activities (p<0.05). Furthermore, the CS-induced phosphorylation of ERK and p38 was also attenuated by silymarin (p<0.05). These results suggest that silymarin attenuated inflammation and oxidative stress induced by cigarette smoke. The anti-inflammatory effect might partly act through the mitogen-activated protein kinases (MAPK) pathway. PMID- 25117570 TI - Liver status in congenital, untreated, isolated GH deficiency. AB - Nonalcoholic fatty liver disease (NAFLD) is known to be associated with insulin resistance, atherosclerosis, and low serum IGF1 levels. We have described a large cohort of patients with isolated GH deficiency (IGHD) due to the c.57+1G->A mutation in the GHRH receptor gene. These subjects have increased insulin sensitivity (IS), delayed atherosclerosis, and normal longevity. We hypothesized that, despite visceral obesity, NAFLD would be absent or mild due to the increased IS. To assess the prevalence and severity of NAFLD in adult subjects with lifetime, congenital, untreated IGHD, we studied 22 IGHD adults and 25 controls (COs) matched for age and sex. NAFLD was assessed by a comprehensive liver function panel, and ultrasonographic pattern (hyperechogenic pattern, HP) coded as follows: 0, absent; 1, mild; 2, moderate; and 3, severe. Compared with COs, IGHD individual had lower serum IGF1 (P<0.0001), higher total cholesterol (P=0.027), lower prothrombin time (P=0.017), and similar activated partial thromboplastin time and fibrinogen values. Alanine transaminase (ALT) values were similar in the two groups, but aspartate transaminase was higher in IGHD (P=0.013). However, more IGHD subjects (7/22) than COs (3/23) had ALT above the upper limit of normal (P=0.044). The prevalence of NAFLD was higher in IGHD than COs (61 vs 29%, P=0.032), and the HP score was higher in IGHD than COs (P=0.041), but severe NAFLD was not observed in any IGHD (or CO) individual. Liver HP score is increased in lifetime, untreated, congenital IGHD, but the increase in transaminases is mild, suggesting a lack of advanced forms of NAFLD. PMID- 25117569 TI - Surface engineering of graphene-based nanomaterials for biomedical applications. AB - Graphene-based nanomaterials have attracted tremendous interest over the past decade due to their unique electronic, optical, mechanical, and chemical properties. However, the biomedical applications of these intriguing nanomaterials are still limited due to their suboptimal solubility/biocompatibility, potential toxicity, and difficulties in achieving active tumor targeting, just to name a few. In this Topical Review, we will discuss in detail the important role of surface engineering (i.e., bioconjugation) in improving the in vitro/in vivo stability and enriching the functionality of graphene-based nanomaterials, which can enable single/multimodality imaging (e.g., optical imaging, positron emission tomography, magnetic resonance imaging) and therapy (e.g., photothermal therapy, photodynamic therapy, and drug/gene delivery) of cancer. Current challenges and future research directions are also discussed and we believe that graphene-based nanomaterials are attractive nanoplatforms for a broad array of future biomedical applications. PMID- 25117572 TI - Hot carriers in epitaxial graphene sheets with and without hydrogen intercalation: role of substrate coupling. AB - The development of graphene electronic devices produced by industry relies on efficient control of heat transfer from the graphene sheet to its environment. In nanoscale devices, heat is one of the major obstacles to the operation of such devices at high frequencies. Here we have studied the transport of hot carriers in epitaxial graphene sheets on 6H-SiC (0001) substrates with and without hydrogen intercalation by driving the device into the non-equilibrium regime. Interestingly, we have demonstrated that the energy relaxation time of the device without hydrogen intercalation is two orders of magnitude shorter than that with hydrogen intercalation, suggesting application of epitaxial graphene in high frequency devices which require outstanding heat exchange with an outside cooling source. PMID- 25117571 TI - Circulating IGF1 and IGF2 and SNP genotypes in men and pregnant and non-pregnant women. AB - Circulating IGFs are important regulators of prenatal and postnatal growth, and of metabolism and pregnancy, and change with sex, age and pregnancy. Single nucleotide polymorphisms (SNPs) in genes coding for these hormones associate with circulating abundance of IGF1 and IGF2 in non-pregnant adults and children, but whether this occurs in pregnancy is unknown. We therefore investigated associations of plasma IGF1 and IGF2 with age and genotype at candidate SNPs previously associated with circulating IGF1, IGF2 or methylation of the INS-IGF2 H19 locus in men (n=134), non-pregnant women (n=74) and women at 15 weeks of gestation (n=98). Plasma IGF1 concentrations decreased with age (P<0.001) and plasma IGF1 and IGF2 concentrations were lower in pregnant women than in non pregnant women or men (each P<0.001). SNP genotypes in the INS-IGF2-H19 locus were associated with plasma IGF1 (IGF2 rs680, IGF2 rs1004446 and IGF2 rs3741204) and IGF2 (IGF2 rs1004446, IGF2 rs3741204 and H19 rs217727). In single SNP models, effects of IGF2 rs680 were similar between groups, with higher plasma IGF1 concentrations in individuals with the GG genotype when compared with GA (P=0.016), or combined GA and AA genotypes (P=0.003). SNPs in the IGF2 gene associated with IGF1 or IGF2 were in linkage disequilibrium, hence these associations could reflect other genotype variations within this region or be due to changes in INS-IGF2-H19 methylation previously associated with some of these variants. As IGF1 in early pregnancy promotes placental differentiation and function, lower IGF1 concentrations in pregnant women carrying IGF2 rs680 A alleles may affect placental development and/or risk of pregnancy complications. PMID- 25117573 TI - Interleukin-6 and other inflammatory markers in diagnosis of periprosthetic joint infection. AB - PURPOSE: The purpose of this study was to evaluate the diagnostic value of interleukin-6 (IL-6) and other inflammatory markers including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WCC) in diagnosis of PJI. METHODS: The study group included 40 patients (21 males, 19 females) admitted for surgical intervention after knee or hip arthroplasties. Patients were subjected to careful history taking, thorough clinical examination and pre-operative laboratory investigations including serum IL-6, CRP, WCC and ESR. Peri-implant tissue specimens were subjected to microbiological culture and histopathological examination. RESULTS: The mean age of patients was 58.4 years (range, 38-72 years). Intra-operative cultures and histopathological examination revealed 11 patients had been infected (PJI) and 29 patients were aseptic failure of prosthesis. Four presumed markers of infection were tested preoperatively: ESR, CRP, WCC, and IL-6. ESR (p = 0.0001), CRP (p = 0.004), WCC (0.0001), and IL 6 (p = 0.0001) were significantly higher in patients with septic revision than those with aseptic failure of the prosthesis. Serum IL-6 (>10.4 pg/ml) reportedly had a sensitivity of 100%, a specificity of 90.9%, a PPV of 79%, a NPV of 100%, and accuracy of 92.5%. CONCLUSIONS: The present study demonstrated that IL-6 has been found to be the most accurate laboratory marker for diagnosing PJI when compared to ESR, CRP, and WCC. IL-6 above 10.4 pg/ml and CRP level above 18 mg/L will identify all patients with PJI and the combination of CRP + IL-6 is an excellent screening test to identify all such patients (sensitivity 100%, NPV 100%). PMID- 25117576 TI - Flicker-Induced Time Dilation Does Not Modulate EEG Correlates of Temporal Encoding. AB - In this study, we used EEG to investigate how visual stimulus dynamics (i.e. flicker) affect the mechanisms of duration perception. Previous studies have demonstrated that flickering visual stimuli are judged longer than equally long non-flickering stimuli. We tested whether this effect of flicker on duration judgments is mediated by changes in temporal encoding during the time interval. Here, temporal encoding refers to the perception of the unfolding of time throughout the temporal interval, also termed the "clock stage" in information processing models of interval timing. We hypothesized that if flicker mediates duration perception by affecting temporal encoding, then the dilation-effect should be reflected by neural correlates of temporal encoding. We presented flickering and steady stimuli in a duration bisection task and found that flicker dilated perceived duration. The EEG analysis allowed us to isolate a putative neural correlate of temporal encoding: a modulation of the amplitude of the contingent negative variation (CNV) by stimuli classified as "long" compared to physically identical stimuli classified as "short". However, flicker did not affect the CNV amplitude, suggesting that flicker does not dilate perceived duration by affecting temporal encoding. Possibly, flicker might affect only later stages of temporal processing such as interval comparison or decision making. PMID- 25117575 TI - Prevalence of femoro-acetabular impingement in international competitive track and field athletes. AB - PURPOSE: The aim of our study was to analyse the prevalence of femoro-acetabular impingement (FAI) in national elite track and field athletes compared to peers using magnetic resonance imaging (MRI) and clinical examination including impingement tests. METHODS: A total of 44 participants (22 national elite track and field athletes and 22 non-athletes) underwent an MRI for radiological findings associated with FAI, including alpha angle, lateral centre edge angle (CEA), findings of labral and cartilage lesions. The study group was furthermore investigated by the hip outcome score (HOS) and a clinical hip examination including range of motion (ROM) and impingement tests. RESULTS: Concerning the cam impingement, there was a significant difference measured by mean alpha angle between the athlete group (52.2 +/- 7.29 degrees ) and the control group (48.1 +/ 5.45 degrees , P = 0.004). Eleven athletes showed a cam impingement, while two probands of the control group had a pincer impingement and one a mixed form (P = 0.0217). There was no statistically significant difference concerning the CEA upon evaluating pincer impingement. Seven track and field athletes had a positive impingement test, whereof three had an increased alpha angle >55 degrees . No participant of the control group showed pathological results in the impingement test (P = 0.0121). CONCLUSIONS: MRI evidence and clinical examination suggest that cam impingement is more common in elite athletes in comparison to non athletes. At a professional level, the intense practice of track and field athletics is susceptible for FAI. PMID- 25117574 TI - Evaluation of intervertebral disc regeneration with implantation of bone marrow mesenchymal stem cells (BMSCs) using quantitative T2 mapping: a study in rabbits. AB - PURPOSE: The aim of the study was to investigate the curative effects of transplantation of bone marrow mesenchymal stem cells (BMSCs) on intervertebral disc regeneration and to investigate the feasibility of the quantitative T2 mapping method for evaluating repair of the nucleus pulposus after implantation of BMSCs. METHODS: Forty-eight New Zealand white rabbits were used to establish the lumber disc degenerative model by stabbing the annulus fibrosus and then randomly divided into four groups, i.e. two weeks afterwards, BMSCs or phosphate buffered saline (PBS) were transplanted into degenerative discs (BMSCs group and PBS group), while the operated rabbits without implantation of BMSCs or PBS served as the sham group and the rabbits without operation were used as the control group. At weeks two, six and ten after operation, the T2 values and disc height indices (DHI) were calculated by magnetic resonance imaging (MRI 3.0 T), and the gene expressions of type II collagen (COL2) and aggrecan (ACAN) in degenerative discs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR). T2 values for the nucleus pulposus were correlated with ACAN or COL2 expression by regression analysis. RESULTS: Cell clusters, disorganised fibres, interlamellar glycosaminoglycan (GAG) matrix and vascularisation were observed in lumber degenerative discs. BMSCs could be found to survive in intervertebral discs and differentiate into nucleus pulposus-like cells expressing COL2 and ACAN. The gene expression of COL2 and ACAN increased during ten weeks after transplantation as well as the T2 signal intensity and T2 value. The DHI in the BMSCs group decreased more slowly than that in PBS and sham groups. The T2 value correlated significantly with the gene expression of ACAN and COL2 in the nucleus pulposus. CONCLUSIONS: Transplantation of BMSCs was able to promote the regeneration of degenerative discs. Quantitative and non-invasive T2 mapping could be used to evaluate the regeneration of the nucleus pulposus with good sensitivity. PMID- 25117577 TI - Dimensions of oppositional defiant disorder in young children: model comparisons, gender and longitudinal invariance. AB - Identifying the latent structure of Oppositional Defiant Disorder (ODD) may have important clinical and research implications. The present study compared existing dimensional models of ODD for model fit and examined the metric and scalar invariance of the best-fitting model. Study participants were a diverse (38.8% minority, 49.1% boys) community sample of 796 children. Parents completed the Child Symptom Inventory and the DISC-YC ODD scales at child ages of 4, 5 and 6-7 years. When comparing single-factor (DSM-IV model), two-factor (oppositional behavior, negative affect), and three-factor models (one with dimensions of oppositional behavior, negative affect, antagonistic behavior; a second with dimensions of irritable, hurtful, and headstrong), the two-factor model showed the best fit. The two-factor model showed configural, metric and scalar invariance across gender and age. Results suggest that, among existing models, ODD is best characterized as two separate dimensions, one behavioral and one affective, which are comparable for both boys and girls in these age groups. PMID- 25117578 TI - Positive affect in infant siblings of children diagnosed with autism spectrum disorder. AB - Research on the expression of positive affect in young children with Autism Spectrum Disorder (ASD) suggests that differences in this domain emerge late in the first year or early in the second year. However, many previous studies in this area employed retrospective research methods and global rating schemes. In the current study, the expression of positive affect was examined prospectively at ages 6, 12, and 18 months in three groups: infant siblings with ASD, infant siblings without ASD, and low-risk comparison infants. Infant siblings were the younger brothers or sisters of children diagnosed with ASD and, therefore, had a higher familial risk of ASD. The frequency and duration of smiles were coded from video excerpts from the Autism Observation Scale for Infants (Bryson, Zwaigenbaum, McDermott, Rombough, and Brian 2008), a standardized, play-based assessment of early signs of ASD. Results indicated that at 12 months, infant siblings with ASD had a lower rate of smiling than the other two groups. At 18 months, infant siblings with ASD continued to display a lower rate of smiling than infant siblings without ASD, but not comparison infants. Overall, these results indicate that infant siblings with ASD demonstrate less positive affect than infant siblings without ASD and low-risk comparison infants at 12 months. This suggests that reduced smiling may be an informative behavioural risk marker for ASD by children's first birthdays and may have implications for our understanding of atypical social development in children with ASD. PMID- 25117579 TI - Highly efficient graphene-based Cu(In, Ga)Se2 solar cells with large active area. AB - Two-dimensional graphene has tremendous potential to be used as a transparent conducting electrode (TCE), owing to its high transparency and conductivity. To date graphene films have been applied to several kinds of solar cells except the Cu(In, Ga)Se2 (CIGS) solar cell. In this work, we present a novel TCE structure consisting of a doped graphene film and a thin layer of poly(methyl methacrylate) (PMMA) to replace the ZnO:Al (AZO) electrode for CIGS. By optimizing the contact between graphene and intrinsic ZnO (i-ZnO), a high power conversion efficiency (PCE) of 13.5% has been achieved, which is among the highest efficiencies of graphene-based solar cells ever reported and approaching those of AZO-based solar cells. Besides, the active area of our solar cells reaches 45 mm(2), much larger than other highly efficient graphene-based solar cells (>10%) reported so far. Moreover, compared with AZO-based CIGS solar cells, the total reflectance of the graphene-based CIGS solar cells is decreased and the quantum efficiency of the graphene-based CIGS is enhanced in the near infrared region (NIR), which strongly support graphene as a competitive candidate material for the TCE in the CIGS solar cell. Furthermore, the graphene/PMMA film can protect the solar cell from moisture, making the graphene-based solar cells much more stable than the AZO based solar cells. PMID- 25117581 TI - Reconstruction of the septum with an autogenous double-layered conchal L-strut. AB - BACKGROUND: One of the most important preconditions for a straight nose is a straight and stable cartilaginous L-shaped frame with sufficient support for the nasal tip and the cartilaginous dorsum. Where the structure of the septal cartilage is destroyed, a sufficient L-strut must be reconstructed. This article presents a technique for reconstruction of an autogenous L-strut using double layered conchal cartilages. METHODS: A retrospective review was conducted with a subsequent follow-up evaluation 10.5-22 months later. The conchal L-strut was used for 26 patients to reconstruct a new septal frame. The full details of the planning process, L-frame construction, and technical data are described together with two typical cases. RESULTS: In all 26 cases, the authors were able to reconstruct a sufficient neoseptum. In 25 cases, the neoseptum remained straight. Only in one case did the anterior border deviate immediately after the operation. No slippage from the nasal spine was found. The anchoring to the nasal bones and the upper lateral cartilages was stable. However, one asymmetric columella base was found, caused by an asymmetric support to the footplates by the transplant. The osteocartilagenous vault was successfully reconstructed in all the patients. Of the 26 patients, 25 described a marked improvement in their nasal breathing. CONCLUSION: The reported technique enables the surgeon to reconstruct the complete cartilagenous L-frame with both conchal cartilages. For certain cases, this technique of autogenous reconstruction of the nasal septum could be a valuable alternative to reconstruction with rib cartilage. PMID- 25117582 TI - Silver confined within zeolite EMT nanoparticles: preparation and antibacterial properties. AB - The preparation of pure zeolite nanocrystals (EMT-type framework) and their silver ion-exchanged (Ag(+)-EMT) and reduced silver (Ag(0)-EMT) forms is reported. The template-free zeolite nanocrystals are stabilized in water suspensions and used directly for silver ion-exchange and subsequent chemical reduction under microwave irradiation. The high porosity, low Si/Al ratio, high concentration of sodium and ultrasmall crystal size of the EMT-type zeolite permitted the introduction of a high amount of silver using short ion-exchange times in the range of 2-6 h. The killing efficacy of pure EMT, Ag(+)-EMT and Ag(0)-EMT against Escherichia coli was studied semi-quantitatively. The antibacterial activity increased with increasing Ag content for both types of samples (Ag(+)-EMT and Ag(0)-EMT). The Ag(0)-EMT samples show slightly enhanced antimicrobial efficacy compared to that of Ag(+)-EMT, however, the differences are not substantial and the preparation of Ag nanoparticles is not viable considering the complexity of preparation steps. PMID- 25117580 TI - TORC1 regulates Pah1 phosphatidate phosphatase activity via the Nem1/Spo7 protein phosphatase complex. AB - The evolutionarily conserved target of rapamycin complex 1 (TORC1) controls growth-related processes such as protein, nucleotide, and lipid metabolism in response to growth hormones, energy/ATP levels, and amino acids. Its deregulation is associated with cancer, type 2 diabetes, and obesity. Among other substrates, mammalian TORC1 directly phosphorylates and inhibits the phosphatidate phosphatase lipin-1, a central enzyme in lipid metabolism that provides diacylglycerol for the synthesis of membrane phospholipids and/or triacylglycerol as neutral lipid reserve. Here, we show that yeast TORC1 inhibits the function of the respective lipin, Pah1, to prevent the accumulation of triacylglycerol. Surprisingly, TORC1 regulates Pah1 in part indirectly by controlling the phosphorylation status of Nem1 within the Pah1-activating, heterodimeric Nem1 Spo7 protein phosphatase module. Our results delineate a hitherto unknown TORC1 effector branch that controls lipin function in yeast, which, given the recent discovery of Nem1-Spo7 orthologous proteins in humans, may be conserved. PMID- 25117583 TI - Revisiting cognitive and adaptive functioning in children and adolescents with autism spectrum disorder. AB - Profiles of performance on the Stanford Binet Intelligence Scales (SB5) and Vineland Adaptive Behavior Scales (VABS) were examined in 73 children and adolescents with autism spectrum disorder. SB5 cognitive profiles were observed to be similar between participants with and without early language delay, but different between participants with and without intellectual disability. With few exceptions, the distribution and cognitive profiles of participants with specific nonverbal IQ-verbal IQ and abbreviated IQ-full scale IQ discrepancy patterns paralleled previous reports. A cognitive functioning advantage over adaptive functioning was observed to be strongest in participants without intellectual disability and older participants. The previously reported VABS "autism profile" was not observed. Current findings clarify previous research and will inform the diagnostic process and treatment planning. PMID- 25117585 TI - In vivo imaging in the rabbit as a model for the study of ovulation-inducing factors. AB - The study of factors responsible for eliciting ovulation in rabbits has been hampered by the lack of a suitable method of monitoring the ovaries in vivo. Ovarian imaging by ultrasound biomicroscopy was used in two experiments designed to determine the effects of seminal plasma on the ovulatory response in rabbits. In Experiment 1, female rabbits were group-housed and treated intramuscularly with saline, gonadotropin releasing hormone (GnRH), or seminal plasma of llamas or rabbits (n = 4 to 6 per group). Rabbits were euthanized eight days later to evaluate the ovarian response by ultrasound biomicroscopy ex situ. No differences among groups were detected in the proportion of rabbits that ovulated or in the number and size of corpora lutea. The high incidence of ovulation in the negative control group was unexpected, and confounded determination of an ovulation inducing effect of seminal plasma. In Experiment 2, female rabbits were caged individually, and treated as in Experiment 1 (n = 5 to 7 per group). The ovarian response was evaluated in vivo by transcutaneous ultrasound biomicroscopy. Ovulation and formation of corpora lutea were detected only in rabbits given GnRH. A preovulatory surge in plasma luteinizing hormone concentration and a post ovulatory rise in plasma progesterone concentration were detected only in rabbits treated with GnRH. Surgical translocation of the ovaries to a subcutaneous position enabled longitudinal assessment of the ovulatory response by ultrasound biomicroscopy. Results clearly documented the effect of physical/social interaction on ovulation in rabbits, and did not support the hypothesis that seminal plasma elicits ovulation in rabbits. PMID- 25117586 TI - Effect of multilevel laboratory rat caging system on the well-being of the singly housed Sprague Dawley rat. AB - Current regulations emphasize that good husbandry practices allow animals to engage in species appropriate postural adjustments without touching the enclosure walls. This study evaluated the well-being of rats housed in a commercially available multilevel rat caging system, with or without access to the upper level of the caging. The evaluation methodologies included assessment of behavioral observations in the home cage, physiological assessment of metabolism and immune function, and determination of the affective state using a spatial cognitive bias assay. The study determined that rats that were provided access to the full multilevel cage during testing after initial restriction to the lower level of the cage demonstrated behavioral changes consistent with a positive affective state, while those with no changes to their housing situation had no significant differences in their affective states. Rats that were consistently housed with access restricted to the lower level of the cage exhibited a tendency to increased neutrophil:lymphocyte ratios as compared with those provided with access to all levels of the multilevel cage. There were no differences in body weight demonstrated between the experimental groups. Overall use of the cage space, as documented through analysis of behavioral observations in the home cage, demonstrated no significant differences in preferred location in the cage during the light or dark cycles, though rats with access to both levels of the cage were significantly more active during the light cycle. The results of this study suggest that the use of a multilevel caging system may improve the well being of rats used in research. PMID- 25117587 TI - Post-operative echocardiographic evaluation of bioprosthetic mitral valve implantation in sheep. AB - The ovine model is generally considered to be the best for testing bioprosthetic heart valve durability. Although echocardiography is the method of choice for the interim evaluation of the valve, literature on sheep echocardiography is scarce. Within the context of a study on treatment of pericardial heart valve prostheses, 19 adolescent sheep underwent transthoracic echocardiography six days after mitral implantation of bioprosthetic valves. Echocardiographic examination was performed under mild anesthesia and animals were put in a right lateral decubitus position. Four images were obtained: right parasternal long axis four and five chamber views, right parasternal long axis view with left ventricular outflow, and right parasternal short axis view through the mitral valve. We measured aortic annulus and velocity time integral over the aortic valve to determine stroke volume, cardiac output and cardiac index. The mitral valve was evaluated through color Doppler imaging for valvular and paravalvular leakages. Pulsed wave spectral Doppler was used for the measurement of velocities, pressures and velocity time integrals. For the evaluation of valve stenosis deceleration time and pressure half-time were determined. Effective orifice area of the mitral valve was derived. And, although not measured, other structures could clearly be visualized: right and left ventricle and atrium, wall thicknesses, tricuspid valve. This study shows that echocardiography in sheep is feasible, and that right parasternal images, obtained in animals in a right lateral decubitus position, are well qualified for the interim evaluation of bioprosthetic valves implanted in the mitral position. Besides the implanted valve, other cardiac structures like atria and ventricles can be visualized and evaluated. PMID- 25117588 TI - Practical precautionary resource management using robust optimization. AB - Uncertainties inherent in fisheries motivate a precautionary approach to management, meaning an approach specifically intended to avoid bad outcomes. Stochastic dynamic optimization models, which have been in the fisheries literature for decades, provide a framework for decision making when uncertain outcomes have known probabilities. However, most such models incorporate population dynamics models for which the parameters are assumed known. In this paper, we apply a robust optimization approach to capture a form of uncertainty nearly universal in fisheries, uncertainty regarding the values of model parameters. Our approach, developed by Nilim and El Ghaoui (Oper Res 53(5):780 798, 2005), establishes bounds on parameter values based on the available data and the degree of precaution that the decision maker chooses. To demonstrate the applicability of the method to fisheries management problems, we use a simple example, the Skeena River sockeye salmon fishery. We show that robust optimization offers a structured and computationally tractable approach to formulating precautionary harvest policies. Moreover, as better information about the resource becomes available, less conservative management is possible without reducing the level of precaution. PMID- 25117589 TI - Early response of soil properties and function to riparian rainforest restoration. AB - Reforestation of riparian zones is increasingly practiced in many regions for purposes of biodiversity conservation, bank stabilisation, and improvement in water quality. This is in spite of the actual benefits of reforestation for recovering underlying soil properties and function remaining poorly understood. Here we compare remnant riparian rainforest, pasture and reforestation plantings aged 2-20 years in an Australian subtropical catchment on ferrosols to determine the extent to which reforestation restores key soil properties. Of the nine soil attributes measured (total nitrogen, nitrate and ammonium concentrations, net nitrification and ammonification rates, organic carbon, bulk density, fine root biomass and water infiltration rates), only infiltration rates were significantly lower in pasture than remnant riparian rainforest. Within reforestation plantings, bulk density decreased up to 1.4-fold and infiltration rates increased up to 60-fold with time post-reforestation. Our results suggest that the main outcome of belowground processes of early reforestation is the recovery of the soils' physical structure, with potential beneficial ecosystem services including reduced runoff, erosion and associated sediment and nutrient loads in waterways. We also demonstrate differential impacts of two commonly planted tree species on a subset of soil properties suggesting that preferential planting of select species could accelerate progress on specific restoration objectives. PMID- 25117590 TI - A technique for the estimation of fractional moving blood volume by using three dimensional power Doppler US. AB - PURPOSE: To (a) demonstrate an image-processing method that can automatically measure the power Doppler signal in a three-dimensional ( 3D three-dimensional ) ultrasonographic (US) volume by using the location of organs within the image and (b) compare 3D three-dimensional fractional moving blood volume ( FMBV fractional moving blood volume ) results with commonly used, unstandardized measures of 3D three-dimensional power Doppler by using the human placenta as the organ of interest. MATERIALS AND METHODS: This is a retrospective study of scans obtained as part of a prospective study of imaging placental biomarkers with US, performed with ethical approval and written informed consent. One hundred forty-three consecutive female patients were examined by using an image-processing technique. Three-dimensional FMBV fractional moving blood volume was measured on the vasculature from the uteroplacental interface to a depth 5 mm into the placenta by using a normalization volume 10 mm outside the uteroplacental interface and compared against the Virtual Organ Computer-aided AnaLysis ( VOCAL Virtual Organ Computer-aided AnaLysis ; GE Healthcare, Milwaukee, Wis) vascularization flow index ( VFI vascularization flow index ). Intra- and interobserver variability was assessed in a subset of 18 volumes. Wilcoxon signed rank test and intraclass correlation coefficients were used to assess measurement repeatability. RESULTS: The mean 3D three-dimensional FMBV fractional moving blood volume value +/- standard deviation was 11.78% +/- 9.30 (range, 0.012%-44.16%). Mean VFI vascularization flow index was 2.26 +/- 0.96 (range, 0.15-6.06). Linear regression of VFI vascularization flow index versus FMBV fractional moving blood volume produced an R(2) value of 0.211 and was significantly different in distribution (P < .001). Intraclass correlation coefficient analysis showed higher FMBV fractional moving blood volume values than VFI vascularization flow index for intra- and interobserver variability; intraobserver values were 0.95 for FMBV fractional moving blood volume (95% confidence interval [ CI confidence interval ]: 0.90, 0.98) versus 0.899 for VFI vascularization flow index (95% CI confidence interval : 0.78, 0.96), and interobserver values were 0.93 for FMBV fractional moving blood volume (95% CI confidence interval : 0.82, 0.97) versus 0.67 for VFI vascularization flow index (95% CI confidence interval : 0.32, 0.86). CONCLUSION: The extension of an existing two-dimensional standardized power Doppler measurement into 3D three-dimensional by using an image-processing technique was shown in an in utero placental study. Three-dimensional FMBV fractional moving blood volume and VFI vascularization flow index produced significantly different results. FMBV fractional moving blood volume performed better than VFI vascularization flow index in repeatability studies. Further studies are needed to assess accuracy against a reference standard. PMID- 25117591 TI - Incidental pancreatic cystic lesions: is there a relationship with the development of pancreatic adenocarcinoma and all-cause mortality? AB - PURPOSE: To establish the effect of incidental pancreatic cysts found by using computed tomographic (CT) and magnetic resonance (MR) imaging on the incidence of pancreatic ductal adenocarcinoma and overall mortality in patients from an inner city urban U.S. tertiary care medical center. MATERIALS AND METHODS: Institutional review board granted approval for the study and waived the informed consent requirement. The study population comprised cyst and no-cyst cohorts drawn from all adults who underwent abdominal CT and/or MR November 1, 2001, to November 1, 2011. Cyst cohort included patients whose CT or MR imaging showed incidental pancreatic cysts; no-cyst cohort was three-to-one frequency matched by age decade, imaging modality, and year of initial study from the pool without reported incidental pancreatic cysts. Patients with pancreatic cancer diagnosed within 5 years before initial CT or MR were excluded. Demographics, study location (outpatient, inpatient, or emergency department), dates of pancreatic adenocarcinoma and death, and modified Charlson scores within 3 months before initial CT or MR examination were extracted from the hospital database. Cox hazard models were constructed; incident pancreatic adenocarcinoma and mortality were outcome events. Adenocarcinomas diagnosed 6 months or longer after initial CT or MR examination were considered incident. RESULTS: There were 2034 patients in cyst cohort (1326 women [65.2%]) and 6018 in no-cyst cohort (3,563 [59.2%] women); respective mean ages were 69.9 years +/- 15.1(standard deviation) and 69.3 years +/- 15.2, respectively (P = .129). The relationship between mortality and incidental pancreatic cysts varied by age: hazard ratios were 1.40 (95% confidence interval [ CI confidence interval ]: 1.13, 1.73) for patients younger than 65 years and 0.97 (95% CI confidence interval : 0.88, 1.07), adjusted for sex, race, imaging modality, study location, and modified Charlson scores. Incidental pancreatic cysts had a hazard ratio of 3.0 (95% CI confidence interval : 1.32, 6.89) for adenocarcinoma, adjusted for age, sex, and race. CONCLUSION: Incidental pancreatic cysts found by using CT or MR imaging are associated with increased mortality for patients younger than 65 years and an overall increased risk of pancreatic adenocarcinoma. PMID- 25117592 TI - Structuring text and standardizing data for clinical and population health applications. PMID- 25117595 TI - Developing eLearning for pressure ulcer prevention and management. AB - The impact of pressure ulcers is psychologically, physically and clinically challenging for both patients and NHS staff. NHS Greater Glasgow and Clyde (NHS GGC), in line with the Scottish Best Practice Statement for the Prevention and Management of Pressure Ulcers ( Quality Improvement Scotland, 2009 ), and the NHS Health Improvement Scotland (2011) Preventing Pressure Ulcers Change Package, launched an awareness campaign throughout the organisation in April 2012 and has more recently adopted a 'zero-tolerance' approach to pressure damage. The tissue viability service in NHS GGC recognised that in order to achieve this aim, education of front-line staff is essential. An educational framework for pressure ulcer prevention was developed for all levels of healthcare staff involved in the delivery of patient care. As a means to support the framework, an initiative to develop web-based eLearning modules has been taken forward. This has resulted in the creation of an accessible, cost-effective, stimulating, relevant, and evidence-based education programme designed around the educational needs of all healthcare staff. In conjunction with the organisation's 'top ten tools' for pressure ulcer prevention and management, the modular online education programme addresses the aims of quality improvement and zero tolerance by supporting the provision of safe and effective person-centered care. PMID- 25117596 TI - Prevention and management of wounds using compression therapy. PMID- 25117597 TI - Use of a coverlet system for the management of skin microclimate. AB - Pressure and shear are the two key extrinsic factors that cause pressure ulcer damage. However, if the resilience of the skin and soft tissue deteriorates, the individual's susceptibility to such pressure damage will increase. The risk is greater if the microclimate at the interface between the skin and the support surface is impaired. This will occur when the skin temperature is elevated and there is excess moisture on the skin surface. Microclimate management therefore plays an important role in pressure ulcer prevention. This article describes how use of a new coverlet system (Skin IQ Microclimate Manager, ArjoHuntleigh) can avoid the accumulation of heat and moisture at the patient/support-surface interface. PMID- 25117594 TI - Treatment adherence among new triptan users: a 2-year cohort study in Taiwan. AB - BACKGROUND: The persistence of triptan use among newly prescribed users is low in the United States and European countries. However, triptan refill patterns in Asian primary care practices have not been well described. METHODS: Data from the National Health Insurance Research Database in Taiwan were used to conduct a retrospective cohort analysis from 2005 to 2008. All participants were followed for 2 years after receiving a new triptan prescription. Refill and 2-year retention rates of newly prescribed triptans were calculated, and predictors of the first triptan refill and 2-year retention were analyzed. RESULTS: Of the 13,951 participants with a new triptan prescription (99.9% sumatriptan), 67.4% were prescribed by a neurologist, 67.4% were prescribed at least one prophylactic agent for migraine. Of them, 34.3% adhered to the newly prescribed triptan at the first refill, 0.01% switched to another triptan, and 40.9% switched to a non triptan acute migraine medication. The 2-year retention rate was 4.0%. The frequency of headache-related neurologic visits for 1 year before the index date, first prescription of triptan or other acute medications, first triptan prescription by a neurologist, and prophylactic use were associated with higher first refill rates. The frequency of headache-related neurologic visits 1 year before the index date and first triptan prescription by a neurologist were related to higher 2-year retention rates. Diabetes mellitus and first triptan prescription at a local medical clinic were associated with reduced probability of continued triptan use at the first refill and 2 years. CONCLUSIONS: Similar to Western societies, the refill and 2-year retention rates were low in new users of triptans. Frequency of neurologic visits and triptan prescription by a neurologist were significant predictors of adherence. PMID- 25117598 TI - Wound imaging: from Waterloo to tomorrow. PMID- 25117599 TI - A vapour-permeable film dressing used on superficial wounds. AB - Films are an extremely versatile dressing type that can be effectively used in the treatment of many superficial wounds, such as skin grafts, surgical wounds and superficial burns; they provide an optimal moist environment to promote healing, act as a barrier to bacteria, and afford protection from urine and faecal contamination. Unfortunately, many film dressings are difficult to handle and use traditional adhesives, which can cause trauma to the wound and surrounding skin, as well as increased wound pain at dressing removal. Mepitel(r) Film is a new, easy-to-use wound dressing designed with Safetac(r) technology that helps to minimise dressing-related trauma and pain and assist undisturbed wound healing. This article presents case studies that examine Mepitel Film's use on a variety of wounds, and reviews the findings of research that was undertaken to evaluate the benefits of using this recently developed dressing. PMID- 25117600 TI - Pressure ulcer grading and appropriate equipment selection. AB - This article explores the process and rationale for designing a poster to support community nurses in selecting appropriate pressure-relieving equipment based on accurate risk assessment and correct pressure ulcer grading. The project was prompted by the requirement to update community nurses' knowledge and ensure pressure-relieving equipment selection was evidence-based and not reliant on personal preference. The 2012 NHS Midlands and East 'Stop the pressure' campaign provided community nurses with a framework for pressure ulcer prevention and management. The attention to support surfaces highlighted the need for appropriate equipment. However the tissue viability team found that the introduction of this pathway alone did not help with the practical issues of appropriate equipment selection. The poster was designed with consideration as to how adults learn, and by looking to the Plan, Do, Study, Act (PDSA) cycle. This provided the framework for enabling new ideas and changes to practice to be tested on a small scale before full implementation. PMID- 25117601 TI - Using an alternating pressure mattress to offload heels in ICU. AB - The heel continues to be one of the most common sites of pressure damage. This article reviews the anatomy and physiology of the heel and explores significant risk factors, including those found in the critically ill patient. Interventions to prevent heel pressure ulceration by offloading the heel are explored. An evaluation of the Nimbus 4 alternating pressure mattress was undertaken within an intensive care unit (ICU) to consider the efficacy of its unique Wound Valve Technology, which is designed to help prevent heel pressure ulceration. During the evaluation period none of the patients using the Nimbus 4 developed a pressure ulcer. Staff observed that the Wound Valves provided effective pressure redistribution and, although the cells frequently needed to be adjusted, patient safety was maintained throughout. The Wound Valves were most effective on patients who were less prone to voluntary movement. PMID- 25117602 TI - Extent of cortical generators visible on the scalp: effect of a subdural grid. AB - The effect of the non-conducting substrate of a subdural grid on the scalp electric potential distribution is studied through simulations. Using a detailed head model and the finite element method we show that the governing physics equations predict an important attenuation in the scalp potential for generators located under the grid, and an amplification for generators located under holes in the skull filled with conductive media. These effects are spatially localized and do not cancel each other. A 4 * 8 cm grid can produce attenuations of 2 to 3 times, and an 8 * 8 cm grid attenuation of up to 8 times. As a consequence, when there is no subdural grid, generators of 4 to 8 cm(2) produce scalp potentials of the same maximum amplitude as generators of 10 to 20 cm(2) under the center of a subdural grid. This means that the minimum cortical extents necessary to produce visible scalp activity determined from simultaneous scalp and subdural recordings can be overestimations. PMID- 25117603 TI - Projecting my envy onto you: neurocognitive mechanisms of an offline emotional egocentricity bias. AB - Humans often project their own beliefs, desires and emotions onto others, indicating an inherent egocentrism. In five studies we investigated the neurocognitive mechanisms underlying emotional egocentricity bias (EEB) and specifically an offline EEB, defined as the projection of one's own tendency to react with a certain emotional response pattern in a given situation onto other people. We used a competitive reaction time game associated with monetary gains and losses that allowed inducing feelings of envy and Schadenfreude. While we found evidence for the first hand experience of envy and Schadenfreude, we also observed an offline bias, that is participants on average projected feelings of envy and Schadenfreude when having to judge others. Importantly the extent of experienced and projected social emotions were highly correlated. This bias was observed when participants were both directly involved and also as an uninvolved party, suggesting the offline bias to be independent of the presently experienced emotion. Under increased time pressure however an online bias emerged whereby participants just projected their presently experienced emotions onto the other. Finally, we show that on the neural level shared neuronal networks underlie the offline EEB at least for envy. Thus, for envy, activity of the same part of anterior insula was sensitive to individual differences both in the experience and the projection of envy. These findings outline the set of circumstances leading to specific types of empathic attribution biases and show that individual differences in the experience of social emotions are predictive of the offline egocentricity bias both on a behavioral as well as a neural level. These data extend present models on the neurocognitive mechanisms of interpersonal understanding in the socio-affective domain. PMID- 25117604 TI - Nasal chondromesenchymal hamartoma in young children: CT and MRI findings and review of the literature. AB - BACKGROUND: Nasal chondromesenchymal hamartoma (NCMH) is an extremely rare benign tumor, primarily diagnosed in young infants and children and it often simulates malignant tumors on imaging. CASE PRESENTATION: We present computerized tomography and magnetic resonance imaging findings of two nasal chondromesenchymal hamartomas in a 5-year-old boy and a 6-week-old girl. CONCLUSIONS: NCMH is a rare, benign tumor-like lesion with good biologic behavior. No recurrence after complete resection or malignant transformation of NCMH has been reported. A correct diagnosis is imperative to avoid unnecessary adjuvant therapy. PMID- 25117605 TI - AFM analysis of the multiple types of molecular interactions involved in rituximab lymphoma therapy on patient tumor cells and NK cells. AB - Rituximab is a monoclonal antibody drug approved for the treatment of patients with lymphomas. Rituximab's main killing mechanism is antibody-dependent cellular cytotoxicity (ADCC). During ADCC, rituximab's fragment antigen binding (Fab) region binds to the CD20 antigen on the tumor cell and its fragment crystallizable (Fc) region binds to the Fc receptor (FcR) on the natural killer (NK) cells. In this study, two types of molecular interactions (CD20-rituximab, FcR-rituximab) involved in ADCC were measured simultaneously on cells prepared from biopsy specimens of lymphoma patients by utilizing atomic force microscopy (AFM) with functionalized tips carrying rituximab. NK cells were detected by specific NKp46 fluorescent labeling and tumor cells were detected by specific ROR1 fluorescent labeling. Based on the fluorescence recognition, the binding affinity and distribution of FcRs on NK cells, and CD20 on tumor cells, were quantitatively measured and mapped. The binding affinity and distribution of FcRs (on NK cells) and CD20 (on tumor cells) were associated with rituximab clinical efficacy. The experimental results provide a new approach to simultaneously quantify the multiple types of molecular interactions involved in rituximab ADCC mechanism on patient biopsy cells, which is of potential clinical significance to predict rituximab efficacy for personalized medicine. PMID- 25117606 TI - Mirandese language and genetic differentiation in Iberia: a study using X chromosome markers. AB - BACKGROUND: In the Iberian Peninsula, the Mirandese dialect, spoken in Miranda do Douro (Portugal) close to the north-eastern border with Spain, has attracted much attention. Aim, subjects and methods: This study focuses on providing further insight into the connections forged between Miranda do Douro and regions in the nearby Province of Zamora. This is in order to better assess the extent to which such relations could have been detained by the current patterns of genetic diversity of the populations, whilst contributing to refining the knowledge on patterns of micro-differentiation within the Peninsula. The genetic characterization of both populations was performed through the analysis of X chromosomal markers: X-STRs and X-indels. RESULTS AND CONCLUSION: The results showed that Miranda do Douro tended to present slightly lower levels of diversity in comparison to the other studied regions, which can be a discreet sign of isolation of that population over the years that might have led the way to the preservation of a language not spoken anywhere else in the country. The analysis of X-STRs particularly brought to light the presence of a subtle population sub structure at the micro-geographical area encompassing the north-eastern border, which seems to portray the importance of the political border as a mechanism withholding gene flow between the two countries. PMID- 25117607 TI - Urodynamics before stress urinary incontinence surgery. AB - PURPOSE OF REVIEW: In patients with symptoms of stress urinary incontinence, there is still a debate regarding the benefit of a multichannel urodynamic investigation prior to surgical management. The purpose of this article is to review recent evidence on this topic. RECENT FINDINGS: Results of two large randomized controlled trials provided evidence that preoperative urodynamics do not improve outcome of incontinence surgery in women with uncomplicated stress urinary incontinence. Furthermore, in this selected group of women, urodynamics hardly lead to deviation of surgery as a primary treatment in case of an indication for operation based on symptoms and signs. Low urethral closure pressures and detrusor overactivity are urodynamic parameters which were associated with impaired cure of symptoms of stress urinary incontinence after surgery. SUMMARY: Preoperative urodynamics do not improve outcome in women with complaints of stress incontinence and do hardly alter the treatment plan. It remains questionable whether a more accurate counselling on the postoperative perspectives counterbalances the disadvantages attended with urodynamics. The routine use in women with uncomplicated stress incontinence should no longer be advised. Preoperative urodynamic evaluation should only be used to answer a specific clinical question or if the results are likely to influence the choice of treatment. PMID- 25117615 TI - Phase-1 study of abiraterone acetate in chemotherapy-naive Japanese patients with castration-resistant prostate cancer. AB - Persistent androgen synthesis under castration status in adrenal gland, testes and tumor cells is thought to be one of the major causes of development and progression of castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA), the prodrug of abiraterone, which is an inhibitor of androgen synthesis enzymes, was evaluated for pharmacokinetics, pharmacodynamics, preliminary efficacy and safety in Japanese patients with CRPC in a phase-1, open-label and dose-escalation study. Chemotherapy-naive Japanese CRPC patients (N = 27) received one of four AA daily doses (250 mg [n = 9], 500 mg [n = 6], 1000 [1 h premeal] mg [n = 6] and 1000 [2 h postmeal] mg [n = 6]) continuously through 28 day treatment cycles. In the first cycle, AA monotherapy was given on days 1-7 for pharmacokinetics, and AA plus prednisone (5 mg twice daily) from days 8 to 28. Of 27 patients, 9 continued treatment with AA until the data cut-off date (18 July 2013). Over the evaluated dose range, plasma abiraterone concentrations increased with dose, with median tmax 2-3 h. At each dose level, mean serum corticosterone concentrations increased, while testosterone and dehydroepiandrosterone sulfate concentrations rapidly decreased following a single AA dose and were further reduced to near the quantification limit on day 8 regardless of the dose. At least 3 patients from each dose-group experienced >=50% prostate-specific antigen reduction, suggesting clinical benefit from AA in Japanese CRPC patients. AA was generally well-tolerated, and, therefore, the recommended AA dosage regimen in Japanese CRPC patients is 1000 mg oral dose under modified fasting conditions (at least 1 h premeal or 2 h postmeal). This study is registered at ClinicalTrials.gov: NCT01186484. PMID- 25117616 TI - Forecasting spring from afar? Timing of migration and predictability of phenology along different migration routes of an avian herbivore. AB - Herbivorous birds are hypothesized to migrate in spring along a seasonal gradient of plant profitability towards their breeding grounds (green wave hypothesis). For Arctic breeding species in particular, following highly profitable food is important, so that they can replenish resources along the way and arrive in optimal body condition to start breeding early. We compared the timing of migratory movements of Arctic breeding geese on different flyways to examine whether flyways differed in the predictability of spring conditions at stopovers and whether this was reflected in the degree to which birds were following the green wave. Barnacle geese (Branta leucopsis) were tracked with solar GPS/ARGOS PTTs from their wintering grounds to breeding sites in Greenland (N = 7), Svalbard (N = 21) and the Barents Sea (N = 12). The numerous stopover sites of all birds were combined into a set of 16 general stopover regions. The predictability of climatic conditions along the flyways was calculated as the correlation and slope between onsets of spring at consecutive stopovers. These values differed between sites, mainly because of the presence or absence of ecological barriers. Goose arrival at stopovers was more closely tied to the local onset of spring when predictability was higher and when geese attempted breeding that year. All birds arrived at early stopovers after the onset of spring and arrived at the breeding grounds before the onset of spring, thus overtaking the green wave. This is in accordance with patterns expected for capital breeders: first, they must come into condition; at intermediate stopovers, arrival with the food quality peak is important to stay in condition, and at the breeding grounds, early arrival is favoured so that hatching of young can coincide with the peak of food quality. Our results suggest that a chain of correlations between climatic conditions at subsequent stopovers enables geese to closely track the green wave. However, the birds' precision of migratory timing seems uninfluenced by ecological barriers, indicating partly fixed migration schedules. These might become non-optimal due to climate warming and preclude accurate timing of long-distance migrants in the future. PMID- 25117617 TI - Aromatase inhibitors for metastatic male breast cancer: molecular, endocrine, and clinical considerations. AB - Male breast cancer is a rare condition. Aromatase inhibitors are widely used for treating metastatic male breast cancer patients. In this setting, their use is not substantiated by prospective clinical trials, but is rather driven by similarities supposedly existing with breast cancer in postmenopausal women. This oversimplified approach was questioned by studies addressing the molecular and endocrine roots of the disease. In this manuscript, we discuss relevant aspects of the current use of aromatase inhibitors in metastatic male breast cancer in light of the most updated evidence on the molecular landscape of the disease and the specific changes in the hormonal background occurring with aging. We further point to strategies for blocking multiple hormonal pathway nodes with the goal of improving their therapeutic potential. We searched PubMed from its inception until March 2014 for relevant literature on the use of aromatase inhibitors in metastatic male breast cancer. Selected terms were combined and used both as medical headings and text words. The reference list of the suitable manuscripts was inspected for further publications. Aromatase inhibitors represent the mainstay of treatment in the metastatic setting. Yet, efforts aimed at sharpening the therapeutic potential of aromatase inhibitors still pose a challenge due to the paucity of data. The choice of dual hormonal (or sequential) therapy combining aromatase inhibitors with a GnRH analogue may represent a valid alterative, particularly if informed by cancer- and patient-related features including molecular, endocrine, and clinic characteristics. PMID- 25117618 TI - Electrodeposition of magnetic, superhydrophobic, non-stick, two-phase Cu-Ni foam films and their enhanced performance for hydrogen evolution reaction in alkaline water media. AB - Two-phase Cu-Ni magnetic metallic foams (MMFs) with tunable composition have been prepared by electrodeposition taking advantage of hydrogen co-evolution as a source of porosity. It is observed that Ni tends to deposit inside the porous network defined by the Cu building blocks. Contact angle measurements reveal that the prepared porous films show a remarkable superhydrophobicity (contact angle values larger than 150 degrees ) and a non-sticking property to aqueous droplets. This behavior is predominately ascribed to the morphology of the films - hierarchical micro/nanoporosity, wall thickness, and spatial arrangement. The electrochemical activity and stability towards hydrogen evolution reaction of the Cu-Ni MMFs has been investigated by cyclic voltammetry in 1 M KOH at 298 K, and the optimal Ni content is found to be 15 at%. Furthermore, all the foam-like films exhibit ferromagnetic behaviour due to the presence of the Ni-rich phase, with coercivity values ranging from 114 Oe to 300 Oe. From the technological point of view, the Cu-Ni MMFs are promising candidates for magnetically-actuated micro/nano-electromechanical systems (MEMS/NEMS) and micro/nanorobotic platforms with a large surface-area to volume ratio or in magnetic sensors or separators. PMID- 25117619 TI - The role of physical activity in the CKD setting. AB - A sedentary lifestyle contributes to the development of cardiovascular disease, hypertension, diabetes and probably cancer in the general population; this cluster of disease may be defined the diseasome of physical inactivity. Also in CKD/ESRD patients physical activity is strikingly low. As a result of growing evidence suggestive of cardiovascular benefit among the CKD population with exercise, the National Kidney Foundation recommended counseling by nephrologists to increase patients' levels of physical activity in their guideline about management of cardiovascular disease. Therefore, to maintain the well-being and functional capacity of renal patients attention should be directed toward maintaining strength and aerobic fitness as well as focusing on renal function and anemia or other comorbidities. All CKD/ESRD patients should be counseled and regularly encouraged by nephrology and dialysis staff to increase their level of physical activity. PMID- 25117620 TI - Acute Carotid Artery Stent Thrombosis Due to Dual Antiplatelet Resistance. AB - Carotid artery stenting (CAS) is a revascularization modality that is an alternative to carotid endarterectomy. The efficacy of CAS in primary and secondary prevention from ischemic stroke has been demonstrated in various trials. Acute thrombosis of CAS is a rare complication that can lead to dramatic and catastrophic consequences. We discuss a case of acute CAS thrombosis in a patient who had previously undergone successful CAS. CAS was performed in a 73 year-old man who had had dysarthria lasting 2 weeks with 95% stenosis in his left internal carotid artery. An acute cerebrovascular event resulting in right-sided hemiplegia developed 24 h after the procedure. Computed tomographic carotid angiography revealed complete occlusion of the stent with thrombus. The cause of stent thrombosis was thought to be antiaggregant resistance to both acetylsalicylic acid and clopidogrel. The most important cause of acute CAS thrombosis is inadequate or ineffective antiaggregant therapy. Evaluating patients who are candidates for CAS for acetylsalicylic acid and clopidogrel resistance may preclude this complication. PMID- 25117621 TI - Transforming growth factor alpha is a critical mediator of radiation lung injury. AB - Radiation fibrosis of the lung is a late toxicity of thoracic irradiation. Epidermal growth factor (EGF) signaling has previously been implicated in radiation lung injury. We hypothesized that TGF-alpha, an EGF receptor ligand, plays a key role in radiation-induced fibrosis in lung. Mice deficient in transforming growth factor (TGF-alpha(-/-)) and control C57Bl/6J (C57-WT) mice were exposed to thoracic irradiation in 5 daily fractions of 6 Gy. Cohorts of mice were followed for survival (n >= 5 per group) and tissue collection (n = 3 per strain and time point). Collagen accumulation in irradiated lungs was assessed by Masson's trichrome staining and analysis of hydroxyproline content. Cytokine levels in lung tissue were assessed with ELISA. The effects of TGF-alpha on pneumocyte and fibroblast proliferation and collagen production were analyzed in vitro. Lysyl oxidase (LOX) expression and activity were measured in vitro and in vivo. Irradiated C57-WT mice had a median survival of 24.4 weeks compared to 48.2 weeks for irradiated TGF-alpha(-/-) mice (P = 0.001). At 20 weeks after irradiation, hydroxyproline content was markedly increased in C57-WT mice exposed to radiation compared to TGF-alpha(-/-) mice exposed to radiation or unirradiated C57-WT mice (63.0, 30.5 and 37.6 MUg/lung, respectively, P = 0.01). C57-WT mice exposed to radiation had dense foci of subpleural fibrosis at 20 weeks after exposure, whereas the lungs of irradiated TGF-alpha (-/-) mice were largely devoid of fibrotic foci. Lung tissue concentrations of IL-1beta, IL-4, TNF-alpha, TGF-beta and EGF at multiple time points after irradiation were similar in C57-WT and TGF-alpha(-/-) mice. TGF-alpha in lung tissue of C57-WT mice rose rapidly after irradiation and remained elevated through 20 weeks. TGF-alpha(-/-) mice had lower basal LOX expression than C57-WT mice. Both LOX expression and LOX activity were increased after irradiation in all mice but to a lesser degree in TGF-alpha( /-) mice. Treatment of NIH-3T3 fibroblasts with TGF-alpha resulted in increases in proliferation, collagen production and LOX activity. These studies identify TGF-alpha as a critical mediator of radiation-induced lung injury and a novel therapeutic target in this setting. Further, these data implicate TGF-alpha as a mediator of collagen maturation through a TGF-beta independent activation of lysyl oxidase. PMID- 25117623 TI - The influence of dose rate on the induction of chromosome aberrations and gene mutation after exposure of plateau phase V79-4 cells with high-LET alpha particles. AB - While protracting exposures of low-LET radiations usually leads to a reduction in their effectiveness for a given dose, for high-LET radiation there is now substantial evidence for what has been called an inverse dose-rate effect, where under certain circumstances there is an increase in carcinogenesis or other biological effects, with decreasing dose rate. This study investigates the influence of dose rate on the induction of chromosome aberrations and gene mutations after irradiation of plateau phase V79-4 cells with high-LET alpha particles. The induction of chromosomal aberrations exhibited a linear relationship with dose and showed evidence of a small but significant conventional dose-rate dependence, with low-dose-rate exposures (0.28 Gy h(-1)) being less effective by about 20% (ratio 0.82 +/- 0.04) compared to acute exposures. However no significant dose-rate effect was observed for cell survival or the induction of mutations in the HPRT gene for low-dose-rate exposure (8.0 * 10(-5) and 1.5 * 10(-2) Gy h(-1) for exposure of 0.36 and 0.69 Gy, respectively) when compared to acute exposures. PMID- 25117622 TI - Wip1 abrogation decreases intestinal tumor frequency in APC(Min/+) mice irrespective of radiation quality. AB - Low-linear energy transfer (low-LET) gamma-ray exposure is a risk factor for colorectal cancer (CRC). Due to their high-LET nature, energetic iron ions found in space are expected to pose greater CRC risks to astronauts undertaking long duration space missions beyond low Earth orbit. Wild-type p53-induced phosphatase 1 (Wip1) is important for cellular DNA damage response and its abrogation has been shown to inhibit spontaneous intestinal tumorigenesis in APC(Min/+) mice, a well-studied mouse model of human CRC. However, the relationship of Wip1 to radiation-induced intestinal tumorigenesis, especially by energetic iron ions, has not been investigated in APC(Min/+) mice. We have previously reported that there is a greater intestinal tumorigenic potential of iron-ion radiation relative to (137)Cs gamma rays, so the purpose of the current study was to investigate whether Wip1 abrogation could influence high-LET dependent intestinal tumorigenesis in APC(Min/+) mice. Intestinal tumor frequency and grade were assessed in APC(Min/+)/Wip1(-/-) mice and results were compared to those in APC(Min/+)/Wip1(+/+) mice after exposure to a mean absorbed dose of 2 Gy from (137)Cs gamma rays or 1.6 Gy from 1 GeV/n iron ions. Cellular differentiation and proliferation were also assessed in the intestinal tumors of sham-irradiated and irradiated mice. Decreased tumor frequency and lower tumor grade were observed in APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. Notably, a similar decrease (~6-fold in both groups) in tumor number was observed in sham-irradiated and gamma-irradiated APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. However, tumorigenesis in the energetic iron-ion exposed group was reduced ~8 fold in APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. A significantly lower proliferation/differentiation index in tumors of iron-ion exposed APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice suggests that reduced proliferation and enhanced differentiation as a result of Wip1 abrogation maybe involved. In conclusion, the current study demonstrated that the absence of Wip1 blocked radiation-induced intestinal tumorigenesis irrespective of radiation quality and has implications for developing preventive strategies against the tumorigenic potential of radiation exposure on earth and in outer space. PMID- 25117624 TI - Modeling dose deposition and DNA damage due to low-energy beta(-) emitters. AB - One of the main issues of low-energy internal emitters concerns the very short ranges of the beta particles, versus the dimensions of the biological targets. Depending on the chemical form, the radionuclide may be more concentrated either in the cytoplasm or in the nucleus of the target cell. Consequently, since in most cases conventional dosimetry neglects this issue it may overestimate or underestimate the dose to the nucleus and hence the biological effects. To assess the magnitude of these deviations and to provide a realistic evaluation of the localized energy deposition by low-energy internal emitters, the biophysical track-structure code PARTRAC was used to calculate nuclear doses, DNA damage yields and fragmentation patterns for different localizations of radionuclides in human interphase fibroblasts. The nuclides considered in the simulations were tritium and nickel-63, which emit electrons with average energies of 5.7 (range in water of 0.42 MUm) and 17 keV (range of 5 MUm), respectively, covering both very short and medium ranges of beta-decay products. The simulation results showed that the largest deviations from the conventional dosimetry occur for inhomogeneously distributed short-range emitters. For uniformly distributed radionuclides selectively in the cytoplasm but excluded from the cell nucleus, the dose in the nucleus is 15% of the average dose in the cell in the case of tritium but 64% for nickel-63. Also, the numbers of double-strand breaks (DSBs) and the distributions of DNA fragments depend on subcellular localization of the radionuclides. In the low- and medium-dose regions investigated here, DSB numbers are proportional to the nuclear dose, with about 50 DSB/Gy for both studied nuclides. In addition, DSB numbers on specific chromosomes depend on the radionuclide localization in the cell as well, with chromosomes located more peripherally in the cell nucleus being more damaged by short-ranged emitters in cytoplasm compared with chromosomes located more centrally. These results illustrate the potential for over- or underestimating the risk associated with low-energy emitters, particularly for tritium intake, when their distribution at subcellular levels is not appropriately considered. PMID- 25117625 TI - Nonhomologous end-joining repair plays a more important role than homologous recombination repair in defining radiosensitivity after exposure to high-LET radiation. AB - DNA double-strand breaks (DSBs) induced by ionizing radiation pose a major threat to cell survival. The cell can respond to the presence of DSBs through two major repair pathways: homologous recombination (HR) and nonhomologous end joining (NHEJ). Higher levels of cell death are induced by high-linear energy transfer (LET) radiation when compared to low-LET radiation, even at the same physical doses, due to less effective and efficient DNA repair. To clarify whether high LET radiation inhibits all repair pathways or specifically one repair pathway, studies were designed to examine the effects of radiation with different LET values on DNA DSB repair and radiosensitivity. Embryonic fibroblasts bearing repair gene (NHEJ-related Lig4 and/or HR-related Rad54) knockouts (KO) were used and their responses were compared to wild-type cells. The cells were exposed to X rays, spread-out Bragg peak (SOBP) carbon ion beams as well as with carbon, iron, neon and argon ions. Cell survival was measured with colony-forming assays. The sensitization enhancement ratio (SER) values were calculated using the 10% survival dose of wild-type cells and repair-deficient cells. Cellular radiosensitivity was listed in descending order: double-KO cells > Lig4-KO cells > Rad54-KO cells > wild-type cells. Although Rad54-KO cells had an almost constant SER value, Lig4-KO cells showed a high-SER value when compared to Rad54 KO cells, even with increasing LET values. These results suggest that with carbon ion therapy, targeting NHEJ repair yields higher radiosensitivity than targeting homologous recombination repair. PMID- 25117626 TI - Ability of 18-fludeoxyglucose positron emission tomography/CT to detect incidental cancer. AB - OBJECTIVE: To determine the prevalence and clinical features of pathologically proven incidental cancer (IC) detected by whole-body fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT, as well as the incidence of false-positive and false-negative results. METHODS: We retrospectively reviewed reports derived from (18)F-FDG PET/CT images of 3079 consecutive patients with known or suspected malignancies for 3 years. Discrete focal uptake indicating IC was identified from reports as well as pathological or clinical diagnoses, and the clinical courses were investigated. The false-positive result was defined as uptake indicating IC but not pathologically confirmed as malignant during follow up. The false-negative result was defined as pathologically proven IC detected by another modality at initial clinical work-up or diagnosed during the follow-up period. RESULTS: We found (18)F-FDG uptake indicating IC in 6.7% of all patients, and IC was pathologically proven in 2.2% of all patients. The most common sites were the colon, lung and stomach. The median survival duration of patients with IC was 42 months. The results were false positive in 4.5% of all patients, and the results were false negative in 2.3% of all patients. CONCLUSION: (18)F-FDG PET/CT is a valuable tool for detecting IC. The rates of false-positive and false negative results are within acceptable range. ADVANCES IN KNOWLEDGE: This is the first report to describe the survival of patients with IC, and the detailed features of false-negative results at actual clinical settings. PMID- 25117627 TI - Prevention of hyperoxia-induced bronchial hyperreactivity by sildenafil and vasoactive intestinal peptide: impact of preserved lung function and structure. AB - OBJECTIVE: Hyperoxia exposure leads to the development of lung injury and bronchial hyperreactivity (BHR) via involvement of nitric oxide (NO) pathway. We aimed at characterizing whether the stimulation of the NO pathway by sildenafil or vasoactive intestinal peptide (VIP) is able to prevent the hyperoxia-induced development of BHR. The respective roles of the preserved lung volume and alveolar architecture, the anti-inflammatory and anti-apoptotic potentials of these treatments in the diminished lung responsiveness were also characterized. MATERIALS AND METHODS: Immature (28-day-old) rats were exposed for 72 hours to room air (Group C), hyperoxia (>95%, Group HC), or hyperoxia with the concomitant administration of vasoactive intestinal peptide (VIP, Group HV) or sildenafil (Group HS). Following exposure, the end-expiratory lung volume (EELV) was assessed plethysmographically. Airway and respiratory tissue mechanics were measured under baseline conditions and following incremental doses of methacholine to assess BHR. Inflammation was assessed by analyzing the bronchoalveolar lavage fluid (BALF), while biochemical and histological analyses were used to characterize the apoptotic and structural changes in the lungs. RESULTS: The BHR, the increased EELV, the aberrant alveolarization, and the infiltration of inflammatory cells into the BALF that developed in Group HC were all suppressed significantly by VIP or sildenafil treatment. The number of apoptotic cells increased significantly in Group HC, with no evidence of statistically significant effects on this adverse change in Groups HS and HV. CONCLUSIONS: These findings suggest that stimulating the NO pathway by sildenafil and VIP exert their beneficial effect against hyperoxia-induced BHR via preserving normal EELV, inhibiting airway inflammation and preserving the physiological lung structure, whereas the antiapoptotic potential of these treatments were not apparent in this process. PMID- 25117628 TI - Defining the recognition elements of Lewis Y-reactive antibodies. AB - Antibody response to carbohydrate antigens is often independent of T cells and the process of affinity/specificity improvement is considered strictly dependent on the germinal centers. Antibodies induced during a T cell-independent type 2 (TI-2) response are less variable and less functionally versatile than those induced with T cell help. The antigen specificity consequences of accumulation of somatic mutations in antibodies during TI-2 responses of Marginal Zone (MZ) B cells is a fact that still needs explanation. Germline genes that define carbohydrate-reactive antibodies are known to sculpt antibody-combining sites containing innate, key side-chain contacts that define the antigen recognition step. However, substitutions associated with MZ B cell derived antibodies might affect the mobility and polyspecificity of the antibody. To examine this hypothesis, we analyzed antibodies reactive with the neolactoseries antigen Lewis Y (LeY) to define the residue subset required for the reactive repertoire for the LeY antigen. Our molecular simulation studies of crystallographically determined and modeled antibody-LeY complexes suggests that the heavy-chain germline gene VH7183.a13.20 and the light-chain Vkappa cr1 germline gene are sufficient to account for the recognition of the trisaccharide-H determinant Types 1-4, while the specificity for LeY is driven by the CDR3 backbone conformation of the heavy chain and not the side chain interactions. These results confirm that these monoclonals use germline-encoded amino acids to recognize simple carbohydrate determinants like trisaccharide-H but relies on somatic mutations in the periphery of the combining site to modify affinity for LeY through electrostatic interactions that leads to their optimized binding. These observations bring further attention to the role of mutations in T-cell independent antibodies to distinguish self from non-self carbohydrate antigens. PMID- 25117629 TI - Solubility assessment and on-line exposure confirmation in a patch-clamp assay for hERG (human ether-a-go-go-related gene) potassium channel inhibition. AB - INTRODUCTION: The hERG (human ether-a-go-go-related gene) potassium channel (KV11.1) is an important anti-target in drug discovery as its inhibition by small molecules has considerable promiscuity and is linked to an increased risk of the potentially fatal ventricular arrhythmia torsade de pointes. Therefore, great efforts are taken in the pharmaceutical industry to early on screen out compounds that block the channel. Early screening activities most often include compounds with sub-optimal physicochemical properties such as limited solubility. Therefore, careful monitoring of achieved compound concentration importantly supports the validity of experimental data. METHODS: A novel principle of exposure confirmation in a constant flow patch-clamp assay for hERG interaction is presented. Quantification is based on-real time UV absorption spectroscopy of the perfusion solution using long light path fiber optic flow cells. Calibration is performed using solutions which are confirmed by turbidometry to be free of precipitates. RESULTS: Turbidometry is shown to be sensitive enough to ensure valid calibration of the UV spectroscopic measurement. For a typical drug-like small molecule (verapamil) it is shown that even 30 nM can be accurately quantified using a 100 cm fiber optic flow cell. DISCUSSION: The combination of turbidometry and long light path fiber optic UV spectroscopy offers accurate, almost real-time exposure determination in a wide range of concentrations with little effort, affordable instrumentation, and no delay for data reporting. For research compounds with challenging physicochemical properties this method provides valuable data to support the validity of the measurements. PMID- 25117630 TI - Radiological analysis of gastrointestinal dysmotility in a model of central nervous dopaminergic degeneration: comparative study with conventional in vivo techniques in the rat. AB - INTRODUCTION: Gastrointestinal (GI) motility disorders include many clinical manifestations associated with various pathologies. They are widespread and can be considered a primary symptom or can be associated to other diseases, such as Parkinson's disease. Understanding the type and site of GI dysmotility is crucial to identify the functional abnormality and to unravel the underlying mechanisms, in order to design adequate therapeutic interventions. METHODS: In the present study, we applied radiological analysis, a common tool in clinical practice, to follow up in vivo the progression of GI dysmotility over time and along the entire GI tract in an animal model of central nervous dopaminergic degeneration and compared these results to those obtained with standard techniques commonly used to assess GI motor functions in small rodents. RESULTS: Our radiological data, showing delayed gastric emptying and constipation, agree with and expand previous information obtained with other functional assays in the same model, suggesting that radiological analysis can be an appropriate method to explore GI dysmotility in animal models of human pathologies. DISCUSSION: In this study we have applied for the first time the GI radiological analysis to an animal model of central nervous dopaminergic degeneration providing a non-invasive/animal preserving approach, ethically more acceptable and useful to follow up the development of GI dysmotility in pathologies evolving over time. PMID- 25117633 TI - Amyloid associated with neoplasia in two captive tricolour sharkminnows Balantiocheilus melanopterus Bleeker. AB - Amyloid associated with pancreatic adenocarcinoma was discovered in two captive adult tricolour sharkminnows Balantiocheilus melanopterus Bleeker found dead in a freshwater display. Enlarged abdomens expanded by bloody ascitic fluid and grossly visible masses of abnormal tissue were present surrounding sections of the stomach and intestine. Histologically, the masses were composed of areas of well-organized exocrine pancreatic acini interspersed with cords of poorly differentiated, spindle-shaped cells that compressed and effaced normal parenchyma. These cells possessed small numbers of cytoplasmic zymogen granules; the exocrine nature of these cells was confirmed using transmission electron microscopy (TEM). Fibrovascular connective tissue of the hepatopancreas and mesenteries was expanded by lightly eosinophilic, hyaline, homogeneous acellular material. Similar material greatly expanded the tunica media of large blood vessels in the hepatopancreas. After staining with Congo red or thioflavin T, this material exhibited red-green dichroism under polarized light or bright green fluorescence under ultraviolet light (255 nm), respectively. The non-branching fibrils, of indeterminate length, had an approximate diameter of 10-20 nm using TEM. Although exocrine pancreatic neoplasia is relatively common in fish, the presence of amyloid is not. To our current knowledge, the latter has not yet been described in association with a neoplastic lesion in fish. PMID- 25117632 TI - The CELSR1 polymorphisms rs6007897 and rs4044210 are associated with ischaemic stroke in Chinese Han population. AB - BACKGROUND: Recently, CELSR1 was identified by genome-wide association studies (GWAS) as a susceptibility gene for ischaemic stroke (IS) in Japanese individuals. AIM: The goal was to examine whether CELSR1 variants are associated with IS in the Chinese Han population. SUBJECTS AND METHODS: This study genotyped two single nucleotide polymorphisms (SNPs) of CELSR1, rs6007897 and rs4044210, in a Chinese sample of 569 IS cases and 581 controls and assessed their genotype and allele associations with IS. RESULTS: The results showed that rs6007897 and rs4044210 variants of CELSR1 were significantly (p < 0.01) associated with IS. These associations remained after adjustment for age, gender, smoking status, hypertension, diabetes mellitus and hypercholesterolemia. In addition, a significant association was observed of rs6007897 and rs4044210 of CELSR1 with large artery atherosclerosis (LAA), a sub-type of IS (p < 0.01). CONCLUSION: Taken together, the present study has proven for the first time that CELSR1 is a susceptibility gene for IS in the Chinese Han population, especially for LAA. PMID- 25117631 TI - In vitro culture of bovine preantral follicles: a review. AB - Preantral follicles are the majority of the ovarian follicle population and their use as a source of homogeneous oocytes for bovine reproductive biotechnologies could result in a substantial advance in this field. However, while in other species embryos and offspring have been produced, in bovine species the results have been limited to the follicular activation of small (primordial) preantral follicles and formation of early antral follicles from large (secondary) preantral follicles after in vitro culture. Therefore, this review will highlight the basic aspects of bovine folliculogenesis by focusing on preantral follicles, the methods of harvesting preantral follicles, the main results from in vitro follicular culture during the last 20 years, and the potential candidate substances (basic supplements, growth factors, and hormones) for improving the efficiency of in vitro follicle growth. PMID- 25117642 TI - Atypical neural responses to vocal anger in attention-deficit/hyperactivity disorder. AB - BACKGROUND: Deficits in facial emotion processing, reported in attention deficit/hyperactivity disorder (ADHD), have been linked to both early perceptual and later attentional components of event-related potentials (ERPs). However, the neural underpinnings of vocal emotion processing deficits in ADHD have yet to be characterised. Here, we report the first ERP study of vocal affective prosody processing in ADHD. METHODS: Event-related potentials of 6-11-year-old children with ADHD (n = 25) and typically developing controls (n = 25) were recorded as they completed a task measuring recognition of vocal prosodic stimuli (angry, happy and neutral). Audiometric assessments were conducted to screen for hearing impairments. RESULTS: Children with ADHD were less accurate than controls at recognising vocal anger. Relative to controls, they displayed enhanced N100 and attenuated P300 components to vocal anger. The P300 effect was reduced, but remained significant, after controlling for N100 effects by rebaselining. Only the N100 effect was significant when children with ADHD and comorbid conduct disorder (n = 10) were excluded. CONCLUSION: This study provides the first evidence linking ADHD to atypical neural activity during the early perceptual stages of vocal anger processing. These effects may reflect preattentive hyper vigilance to vocal anger in ADHD. PMID- 25117641 TI - Anti-tumor activity of WK88-1, a novel geldanamycin derivative, in gefitinib resistant non-small cell lung cancers with Met amplification. AB - Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been introduced for the treatment of non-small cell lung cancer (NSCLC), the emergence of secondary T790M mutation in EGFR or amplification of the Met proto oncogene restrain the clinical success of EGFR-TKIs. Since heat shock protein-90 (Hsp90) stabilizes various oncoproteins including EGFR and c-Met, the inhibition of Hsp90 activity appears as a rational strategy to develop anticancer drugs. Despite preclinical efficacy of geldanamycin-anasamycin (GA)-derivatives containing benzoquinone moiety as Hsp90 inhibitors, the hepatotoxicity of these GA-derivatives restricts their therapeutic benefit. We have prepared WK-88 series of GA-derivatives, which lack the benzoquinone moiety. In this study, we have examined the anticancer effects of WK88-1 in Met-amplified- and gefitinib resistant (HCC827GR) NSCLC cells and its parental HCC827 cells. Treatment with WK88-1 reduced the cell viability in both HCC827 and HCC827GR cells, which was associated with marked decrease in the constitutive expression of Hsp90 client proteins, such as EGFR, ErbB2, ErbB3, Met and Akt. Moreover, WK88-1 attenuated phosphorylation of these Hsp90 client proteins and reduced the anchorage independent growth of HCC827GR cells. Administration of WK88-1 did not cause hepatotoxicity in animals and significantly reduced the growth of HCC827GR cells xenograft tumors in nude mice. Our study provides evidence that ErbB3 might be a client for Hsp90 in Met-amplified NSCLCs. In conclusion, we demonstrate that inhibition of Hsp90 dampens the activation of EGFR- or c-Met-mediated survival of Met-amplified NSCLCs and that WK88-1 as a Hsp90 inhibitor alleviates gefitinib resistance in HCC827GR cells. PMID- 25117644 TI - Mystery of myocardial midwall late enhancement? PMID- 25117643 TI - Computer-aided CT coronary artery stenosis detection: comparison with human reading and quantitative coronary angiography. AB - To evaluate computer-aided stenosis detection for computed tomography coronary angiography (CTA) in comparison with human reading and conventional coronary angiography (CCA) as the reference standard. 50 patients underwent CTA and CCA and out of these 44 were evaluable for computer-aided stenosis detection. The diagnostic performance of the software and of human reading were compared and quantitative coronary angiography (QCA) served as the reference standard for the detection of significant stenosis (>50 %). Overall, three readers with high (reader 1), intermediate (reader 2) and low (reader 3) experience in cardiac CT imaging performed the manual CTA evaluation on a commercially available workstation, whereas the automated software processed the datasets without any human interaction. The prevalence of coronary artery disease was 41 % (18/44) and QCA indicated significant stenosis (>50 %) in 33 coronary vessels. The automated software accurately diagnosed 18 individuals with significant coronary artery disease (CAD), and correctly ruled out CAD in 10 patients. In summary the sensitivity of computer-aided detection was 100 %/94 % (per-patient/per-vessel) and the specificity was 38 %/70 %, the positive predictive value (PPV) was 53 %/42 % and the negative predictive value (NPV) was 100 %/98 %. In comparison, reader 1-3 showed per-patient sensitivities of 100/94/89 %, specificities of 73/69/50 %, PPVs of 72/68/55 % and NPVs of 100/95/87 %. Computer-aided detection yields a high NPV that is comparable to more experienced human readers. However, PPV is rather low and in the range of an unexperienced reader. PMID- 25117647 TI - Hierarchically porous three-dimensional electrodes of CoMoO4 and ZnCo2O4 and their high anode performance for lithium ion batteries. AB - Ternary metal oxides have been receiving wide attention in electrochemical energy storage due to their rich redox reactions and tuneable conductivity. We present a simple solution-based method to prepare a 3D interconnected porous network of ternary metal oxide (CoMoO4 and ZnCo2O4) nanostructures on macroporous nickel foam. The open-structured networks with different degrees of porosity endow them with high surface areas of electro-active sites. The Li ion storage properties of both anodes are investigated. High rate capability and long term cycling stability are achieved for both systems. PMID- 25117648 TI - Nutrition and physical activity in CKD patients. AB - Chronic kidney disease (CKD) patients are at risk for protein-energy wasting, abnormal body composition and impaired physical capacity. These complications lead to increased risk of hospitalization, morbidity and mortality.In CKD patient as well as in healthy people, there is a close association between nutrition and physical activity. Namely, inadequate nutrient (energy) intake impairs physical performance thus favoring a sedentary lifestyle: this further contributes to loss of muscle strength and mass, which limit the quality of life and rehabilitation of CKD patients. In CKD as well as in end-stage-renal-disease patients, regular physical activity coupled with adequate energy and protein intake counteracts protein-energy wasting and related comorbidity and mortality. In summary, exercise training can positively influence nutritional status and the perception of well-being of CKD patients and may facilitate the anabolic effects of nutritional interventions. PMID- 25117646 TI - Tubal transport of gametes and embryos: a review of physiology and pathophysiology. AB - With the advent of assisted reproductive technology in the past three decades, the clinical importance of fallopian tubes has been relatively overlooked. However, successful spontaneous conception requires normal function of the tube to provide not only a conduit for the gametes to convene and embryo to reach the uterine cavity, but also a physiologically optimized environment for fertilization and early embryonic development. In this review, after a brief description of normal human tubal anatomy and histology, we will discuss tubal transport and its principal effectors, including ciliary motion, muscular contractility and tubal fluid. Furthermore, we will discuss the ciliary ultrastructure and regulation of ciliary beat frequency by ovarian steroids, follicular fluid, angiotensin system, autonomic nervous system and other factors such as adrenomedullin and prostaglandins. In the last section, we describe the adverse impact of various pathological conditions, such as endometriosis, infection and smoking on tubal function and ciliary motility. PMID- 25117650 TI - Oxidative stress and antioxidant status in patients with autoimmune liver diseases. AB - OBJECTIVE: To estimate oxidative stress and antioxidant components during different stages of autoimmune liver diseases and assess their possible implication on disease progression. METHODS: We determined several markers of oxidative injury (isoprostane, aldehydes, protein carbonyls, 3-nitrotyrosine, and myeloperoxidase) and antioxidant components (glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase) in whole blood, serum, and urine in 49 patients with autoimmune cholestatic liver diseases (AC) and 36 patients with autoimmune hepatitis (AIH) and healthy subjects matched for sex and age. RESULTS: Both AC and AIH patients had increased levels of all lipid and protein oxidative injury products and significantly decreased whole blood glutathione levels compared to controls. AIH patients had significantly higher levels of aldehydes and glutathione peroxidase activity and significantly lower protein carbonyl levels compared to AC patients. Protein carbonyl and isoprostane levels increased and glutathione levels decreased gradually with progression from mild fibrosis to severe fibrosis and cirrhosis in both AC and AIH patients. In addition, both cirrhotic AC and AIH patients had significantly higher protein carbonyls compared to non-cirrhotics. DISCUSSION: We provide novel findings in support of a major contribution of oxidant/antioxidant imbalance in the progression of liver injury in AC and AIH. PMID- 25117651 TI - Anatomic connectivity assessed using pathway radial diffusivity is related to functional connectivity in monosynaptic pathways. AB - This work presents a pathway-dependent anatomic and functional connectivity analysis in 19 patients with relapse-remitting multiple sclerosis (MS) and 16 age , education-, and gender-matched controls. An MS population is used in this study as a model for anatomic connectivity, permitting us to observe relationships between anatomic and functional connectivity more easily. A combined resting state functional magnetic resonance imaging (fMRI) and whole-brain, high angular resolution diffusion imaging analysis is performed in three independent, monosynaptic pathways. The pathways chosen were transcallosal pathway connecting the bilateral primary sensorimotor regions, right and left posterior portion of the Papez circuit, connecting the posterior cingulate cortex and hippocampus. The Papez circuit is known to be involved in memory function, one of the most frequently impacted cognitive domains in patients with MS. We show that anatomic connectivity, as measured with diffusion-weighted imaging, and functional connectivity, as measured with resting-state fMRI, are significantly reduced in patients as compared with controls for at least some of the pathways considered. In addition when all pathway measures are combined, anatomic and functional connectivity are significantly correlated in patients with MS as well as healthy controls. We suggest that anatomic and functional connectivity are related for monosynaptic pathways and that radial diffusivity, as a diffusion-tensor-based measure of white matter integrity, is a robust measure of anatomic connectivity in the general population. PMID- 25117649 TI - Effects of 20 standard amino acids on the growth, total fatty acids production, and gamma-linolenic acid yield in Mucor circinelloides. AB - Twenty standard amino acids were examined as single nitrogen source on the growth, total fatty acids production, and yield of gamma-linolenic acid (GLA) in Mucor circinelloides. Of the amino acids, tyrosine gave the highest biomass and lipid accumulation and thus resulted in a high GLA yield with respective values of 17.8 g/L, 23 % (w/w, dry cell weight, DCW), and 0.81 g/L, which were 36, 25, and 72 % higher than when the fungus was grown with ammonium tartrate. To find out the potential mechanism underlying the increased lipid accumulation of M. circinelloides when grown on tyrosine, the activity of lipogenic enzymes of the fungus during lipid accumulation phase was measured. The enzyme activities of glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and ATP citrate lyase were up-regulated, while NADP-isocitrate dehydrogenase was down regulated by tyrosine during the lipid accumulation phase of the fungus which suggested that these enzymes may be involved in the increased lipid biosynthesis by tyrosine in this fungus. PMID- 25117645 TI - A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART). AB - BACKGROUND: The assisted reproductive techniques aimed to assist infertile couples have their own offspring carry significant risks of passing on molecular defects to next generations. RESULTS: Novel breakthroughs in gene and protein interactions have been achieved in the field of male infertility using genome wide proteomics and transcriptomics technologies. CONCLUSION: Male Infertility is a complex and multifactorial disorder. SIGNIFICANCE: This review provides a comprehensive, up-to-date evaluation of the multifactorial factors involved in male infertility. These factors need to be first assessed and understood before we can successfully treat male infertility. PMID- 25117653 TI - The indications, efficacy and adverse events of rituximab in a large cohort of patients with juvenile-onset SLE. AB - BACKGROUND: B cells drive antibody formation and T cell activation. This study aimed to describe the clinical indications, efficacy and adverse events (AEs) for the B-cell depleting agent, rituximab, in a large cohort of children with lupus. METHODS: Prescribing records and the UK JSLE Cohort Study database identified rituximab use. RESULTS: Sixty-three patients received 104 courses of intravenous rituximab over a 10-year period. Patients were aged 12.2 (IQR 9.0-13.9) years at diagnosis and 50 (79%) were female. They had disease for 1.4 (0.2-3.0) years at the time of rituximab. Lupus nephritis was the most common indication (36% of first courses). Clinical biomarkers, 2.5 (1.6-4.3) months after treatment, demonstrated a statistically significant improvement in ESR, C3, C4, creatinine, albumin, haemoglobin, anti-dsDNA titres and urine albumin:creatinine ratio. IgG, IgA and IgM levels decreased (p < 0.01). Oral corticosteroid dose significantly reduced after rituximab (dose before 0.26 (0.09-0.44) mg/kg, after 0.17 (0.09 0.30) mg/kg; p = 0.01)). AEs occurred in 19 (18%) of all courses including; delayed second dose (8%), Ig replacement (2%) and infusion reactions (6%; anaphylaxis 2%). The global BILAG score showed a trend toward improvement (before 4.5 (2.0-9.0), after 3.0 (2.0-5.0); p = 0.16). CONCLUSION: Rituximab improves disease activity in children with lupus and serious AEs are infrequent. Controlled studies are required. PMID- 25117652 TI - Heck products of parthenolide and melampomagnolide-B as anticancer modulators that modify cell cycle progression. AB - (E)-13-(Aryl/heteroaryl)parthenolides (5a-i and 6a-i) were synthesized and evaluated for their ability to modify cell cycle progression during progesterone stimulated Xenopus oocyte maturation and screened for their anticancer activity against a panel of 60 human cancer cell lines. (E)-13-(4-aminophenyl) parthenolide (5b) caused a significant inhibition of progesterone-stimulated oocyte maturation, and was determined to function downstream of MAP kinase signaling, but upstream of the activation of the universal G2/M regulator, M phase promoting factor (MPF), cyclin B/Cyclin-dependent kinase (CDK). The compound (E)-13-(2-bromo-phenyl)parthenolide (5c) activates oocyte maturation independently of progesterone stimulation. Compounds 5b and 5c displayed modest growth inhibition on select cancer cell lines at 10 MUM dose when tested on the panel of 60 cancer cell lines. By contrast, compounds (5f and 7) did not modulate oocyte maturation but did exhibit micromolar level growth inhibition against most of the human cancer cell lines over a range of doses. Together, our findings indicate that screening of compounds in the oocyte maturation assay may identify additional effective cell cycle regulatory compounds that do not necessarily exert overt cytotoxicity as assessed in traditional drug screening assays. PMID- 25117654 TI - Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients. AB - BACKGROUND: Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. PATIENTS AND METHODS: Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation unrelated disability was considered as 'unfavourable neurological outcome'. RESULTS: Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. CONCLUSION: Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use. PMID- 25117655 TI - Thrombopoietin levels in systemic lupus erythematosus are linked to inflammatory cytokines, but unrelated to thrombocytopenia or thrombosis. AB - BACKGROUND: Thrombopoietin (TPO) is a liver-produced protein that drives megakaryocyte maturation. TPO regulates platelet production and can increase platelet and endothelial reactivity. We investigated the relationship between TPO and the occurrence of thrombocytopenia and thrombosis in patients with systemic lupus erythematosus (SLE). METHODS: We undertook a cohort study of SLE patients (n = 98) with clinical data collected simultaneously with sampling for TPO, inflammatory cytokines and autoantibody detection. TPO levels were measured by sandwich ELISA with patients with rheumatoid arthritis (RA) (n = 100) and controls (n = 79) as comparators. Disease associations were evaluated using non parametric methods. RESULTS: TPO levels in SLE (median 8 pg/ml, mean 326, range 8992) were moderately increased compared with RA (median 8 pg/ml, mean 100, range 1659, p = 0.07) and controls (median 8, mean 94, range 2088, p = 0.1). Among SLE patients, TPO levels did not correlate with platelet count or levels of antiphospholipid antibodies. The prevalence of thrombocytopenic episodes, thrombotic events or active disease was not increased in patients with high TPO levels. TPO levels correlated with MIP-1alpha (Rs 0.56, p < 0.001), IL6 (Rs 0.26, p = 0.02) and IL4 (Rs 0.29, p = 0.01), and inversely correlated to C4 (Rs -0.23, p = 0.04). MIP-1alpha was the strongest independent predictor of increased TPO levels. CONCLUSION: TPO levels are elevated in 20% of patients, but are not closely related to the occurrence of thrombocytopenia or thrombosis in SLE. MIP1 alpha is the main factor driving higher TPO levels among patients with SLE, likely through its inhibitory effect on megakaryocyte function. PMID- 25117656 TI - miRPlant: an integrated tool for identification of plant miRNA from RNA sequencing data. AB - BACKGROUND: Small RNA sequencing is commonly used to identify novel miRNAs and to determine their expression levels in plants. There are several miRNA identification tools for animals such as miRDeep, miRDeep2 and miRDeep*. miRDeep P was developed to identify plant miRNA using miRDeep's probabilistic model of miRNA biogenesis, but it depends on several third party tools and lacks a user friendly interface. The objective of our miRPlant program is to predict novel plant miRNA, while providing a user-friendly interface with improved accuracy of prediction. RESULT: We have developed a user-friendly plant miRNA prediction tool called miRPlant. We show using 16 plant miRNA datasets from four different plant species that miRPlant has at least a 10% improvement in accuracy compared to miRDeep-P, which is the most popular plant miRNA prediction tool. Furthermore, miRPlant uses a Graphical User Interface for data input and output, and identified miRNA are shown with all RNAseq reads in a hairpin diagram. CONCLUSIONS: We have developed miRPlant which extends miRDeep* to various plant species by adopting suitable strategies to identify hairpin excision regions and hairpin structure filtering for plants. miRPlant does not require any third party tools such as mapping or RNA secondary structure prediction tools. miRPlant is also the first plant miRNA prediction tool that dynamically plots miRNA hairpin structure with small reads for identified novel miRNAs. This feature will enable biologists to visualize novel pre-miRNA structure and the location of small RNA reads relative to the hairpin. Moreover, miRPlant can be easily used by biologists with limited bioinformatics skills.miRPlant and its manual are freely available at http://www.australianprostatecentre.org/research/software/mirplant or http://sourceforge.net/projects/mirplant/. PMID- 25117658 TI - Knuiman et al. respond to "Time-varying neighborhood environments". PMID- 25117657 TI - Characterization of the rapid transcriptional response to long-term sensitization training in Aplysia californica. AB - We used a custom-designed microarray and quantitative PCR to characterize the rapid transcriptional response to long-term sensitization training in the marine mollusk Aplysia californica. Aplysia were exposed to repeated noxious shocks to one side of the body, a procedure known to induce a long-lasting, transcription dependent increase in reflex responsiveness that is restricted to the side of training. One hour after training, pleural ganglia from the trained and untrained sides of the body were harvested; these ganglia contain the sensory nociceptors which help mediate the expression of long-term sensitization memory. Microarray analysis from 8 biological replicates suggests that long-term sensitization training rapidly regulates at least 81 transcripts. We used qPCR to test a subset of these transcripts and found that 83% were confirmed in the same samples, and 86% of these were again confirmed in an independent sample. Thus, our new microarray design shows strong convergent and predictive validity for analyzing the transcriptional correlates of memory in Aplysia. Fully validated transcripts include some previously identified as regulated in this paradigm (ApC/EBP and ApEgr) but also include novel findings. Specifically, we show that long-term sensitization training rapidly up-regulates the expression of transcripts which may encode Aplysia homologs of a C/EBPgamma transcription factor, a glycine transporter (GlyT2), and a vacuolar-protein-sorting-associated protein (VPS36). PMID- 25117660 TI - A longitudinal analysis of the influence of the neighborhood built environment on walking for transportation: the RESIDE study. AB - The purpose of the present analysis was to use longitudinal data collected over 7 years (from 4 surveys) in the Residential Environments (RESIDE) Study (Perth, Australia, 2003-2012) to more carefully examine the relationship of neighborhood walkability and destination accessibility with walking for transportation that has been seen in many cross-sectional studies. We compared effect estimates from 3 types of logistic regression models: 2 that utilize all available data (a population marginal model and a subject-level mixed model) and a third subject level conditional model that exclusively uses within-person longitudinal evidence. The results support the evidence that neighborhood walkability (especially land-use mix and street connectivity), local access to public transit stops, and variety in the types of local destinations are important determinants of walking for transportation. The similarity of subject-level effect estimates from logistic mixed models and those from conditional logistic models indicates that there is little or no bias from uncontrolled time-constant residential preference (self-selection) factors; however, confounding by uncontrolled time varying factors, such as health status, remains a possibility. These findings provide policy makers and urban planners with further evidence that certain features of the built environment may be important in the design of neighborhoods to increase walking for transportation and meet the health needs of residents. PMID- 25117659 TI - Invited commentary: Taking advantage of time-varying neighborhood environments. AB - Neighborhood built environment characteristics may encourage physical activity, but previous literature on the topic has been critiqued for its reliance on cross sectional data. In this issue of the Journal, Knuiman et al. (Am J Epidemiol. 2014;180(5):453-461) present longitudinal analyses of built environment characteristics as predictors of neighborhood transportation walking. We take this opportunity to comment on self-selection, exposure measurement, outcome form, analyses, and future directions. The Residential Environments (RESIDE) Study follows individuals as they relocate into new housing. The outcome, which is neighborhood transportation walking, has several important limitations with regards to public health relevance, dichotomization, and potential bias. Three estimation strategies were pursued: marginal modeling, random-effects modeling, and fixed-effects modeling. Knuiman et al. defend fixed-effects modeling as the one that most effectively controls for unmeasured time-invariant confounders, and it will do so as long as confounders have a constant effect over time. Fixed effects modeling requires no distributional assumptions regarding the heterogeneity of subject-specific effects. Associations of time-varying neighborhood characteristics with walking are interpreted at the subject level for both fixed- and random-effects models. Cross-sectional data have set the stage for the next generation of neighborhood research, which should leverage longitudinal changes in both place and health behaviors. Careful interpretation is warranted as longitudinal data become available for analysis. PMID- 25117661 TI - Research for better health: the Panamanian priority-setting experience and the need for a new process. AB - BACKGROUND: Panama is, economically, the fastest growing country in Central America and is making efforts to improve management mechanisms for research and innovation. However, due to contextual factors, the Panamanian Health Research System is not well developed and is poorly coordinated with the Health System. Likewise, despite recent efforts to define a National Health Research Agenda, implementing this agenda and aligning it with Panamanians' health needs remains difficult. This articles aims to review Panama's experience in health research priority setting by analyzing the fairness of previous prioritization processes in order to promote an agreed-upon national agenda aligned with public health needs. METHODS: The three health research prioritization processes performed in Panama between 2006 and 2011 were analyzed based on the guidelines established by the four "Accountability for Reasonableness" principles, namely "relevance", "publicity", "revision", and "enforcement", which provide a framework for evaluating priority-setting fairness. RESULTS: The three health research priority setting events performed in Panama during the reference period demonstrated a heterogeneous pattern of decision-making strategies, stakeholder group composition, and prioritization outcomes. None of the three analyzed events featured an open discussion process with the scientific community, health care providers, or civil society in order to reach consensus. CONCLUSIONS: This investigation makes evident the lack of a strategy to encourage open discussion by the multiple stakeholders and interest groups that should be involved during the priority-setting process. The analysis reveals the need for a new priority setting exercise that validates the National Agenda, promotes its implementation by the National Secretariat for Science, Technology and Innovation in conjunction with the Ministry of Health, and empowers multiple stakeholders; such an exercise would, in turn, favor the implementation of the agenda. PMID- 25117663 TI - Utilization of stem cells to treat congenital heart disease: hype and hope. AB - PURPOSE OF REVIEW: Surgical advances over the past few decades have transformed the clinical management of congenital heart disease, such as hypoplastic left heart syndrome. Congenital heart disease affects more than 1% of liveborn infants and accounts for more than 2.5 million affected children per year worldwide. The cost and availability of complex medical management for these children becomes bluntly realized when heart failure progresses and only palliative options remain. Cell-based cardiac regeneration has been the focus of intensive efforts in adult heart disease for more than a decade and now has promise for pediatrics. RECENT FINDINGS: Innate cardiac regeneration in the pediatric setting is measurable and potentially modifiable in the early stages of development. Repurposing cell-based manufactured products to promote cardiac regeneration in congenital heart disease has demonstrated significant improvement in cases of dilated cardiomyopathy and structural heart disease in infants. SUMMARY: A focus on preemptive cardiac regeneration in the pediatric setting may offer new insights into the timing of surgery, location of cell-based delivery, and type of cell-based regeneration that could further inform acquired cardiac disease applications. The concept of cell-based pediatric cardiac regenerative surgery could transform the management of congenital heart disease when cost-effective strategies produce a valuable adjunctive solution to improve outcomes of cardiac surgery. PMID- 25117662 TI - Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation. AB - Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFalpha production following LPS stimulation. We found that MTA could block TNFalpha production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1beta production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation. PMID- 25117664 TI - Genetic variation in dihydropyrimidine dehydrogenase (DPYD) gene in a healthy adult Indian population. AB - BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) encoded by DPYD gene is the major enzyme involved in metabolism of 5-flurouracil (5-FU), a pyrimidine analogue used in cancer chemotherapy. Although very effective as a cancer therapeutic drug, if not rapidly metabolized, 5-FU may prove lethal. Single nucleotide variants (SNVs) within DPYD that modulate DPD enzyme activity contribute to 5-FU toxicity. STUDY: This study looked for DPYD SNVs common in the Indian population that might be associated with variable DPD activity and drug toxicity. To achieve this, sequencing analysis was performed of all 23 exons and flanking intronic regions of the DPYD gene in a cohort of 50 healthy adult Indians. This study detected 22 SNVs including intronic, synonymous and non synonymous changes in the DPYD gene, of which six have not been documented before. Allelic frequency was calculated for the observed variants and linkage disequilibrium (LD) analysis was performed on variants with frequency >=0.1 to identify haplotypes. CONCLUSIONS: This study provides a brief overview of the genetic polymorphism in DPYD in Indians and emphasizes the need for a large scale extensive study to establish markers associated with the frequently observed variable drug metabolism. PMID- 25117665 TI - Infection and pathology in Queensland grouper, Epinephelus lanceolatus, (Bloch), caused by exposure to Streptococcus agalactiae via different routes. AB - Since 2007, 96 wild Queensland groupers, Epinephelus lanceolatus, (Bloch), have been found dead in NE Australia. In some cases, Streptococcus agalactiae (Group B Streptococcus, GBS) was isolated. At present, a GBS isolate from a wild grouper case was employed in experimental challenge trials in hatchery-reared Queensland grouper by different routes of exposure. Injection resulted in rapid development of clinical signs including bilateral exophthalmia, hyperaemic skin or fins and abnormal swimming. Death occurred in, and GBS was re-isolated from, 98% fish injected and was detected by PCR in brain, head kidney and spleen from all fish, regardless of challenge dose. Challenge by immersion resulted in lower morbidity with a clear dose response. Whilst infection was established via oral challenge by admixture with feed, no mortality occurred. Histology showed pathology consistent with GBS infection in organs examined from all injected fish, from fish challenged with medium and high doses by immersion, and from high-dose oral challenge. These experimental challenges demonstrated that GBS isolated from wild Queensland grouper reproduced disease in experimentally challenged fish and resulted in pathology that was consistent with that seen in wild Queensland grouper infected with S. agalactiae. PMID- 25117675 TI - Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non alcoholic steatohepatitis. AB - Non-alcoholic steatohepatitis (NASH) has emerged as a common cause of chronic liver disease and virus-independent hepatocellular carcinoma (HCC) in patients with obesity, diabetes, and metabolic syndrome. To reveal the molecular mechanism underlying hepatocarcinogenesis from NASH, microRNA (miRNA) expression profiles were analyzed in STAM mice, a NASH-HCC animal model. MicroRNA expression was also examined in 42 clinical samples of HCC tissue. Histopathological images of the liver of STAM mice at the ages of 6, 8, 12, and 18 weeks showed findings compatible with fatty liver, NASH, liver cirrhosis (LC), and HCC, respectively. Expression of miR-122 in non-tumor LC at the age of 18 weeks was significantly lower than that in LC at the age of 12 weeks. Expression of miR-122 was further decreased in HCCs relative to non-tumor LC at the age of 18 weeks. Expression of miR-122 was also decreased in clinical samples of liver tissue showing macrovesicular steatosis and HCC, being consistent with the findings in the NASH model mice. DNA methylation analysis revealed that silencing of miR-122 was not mediated by DNA hypermethylation of the promoter region. These results suggest that silencing of miR-122 is an early event during hepatocarcinogenesis from NASH, and that miR-122 could be a novel molecular marker for evaluating the risk of HCC in patients with NASH. PMID- 25117677 TI - Paternal factor V Leiden and recurrent pregnancy loss: a new concept behind fetal genetics? Reply. PMID- 25117676 TI - Sparstolonin B attenuates hypoxia-induced apoptosis, necrosis and inflammation in cultured rat left ventricular tissue slices. AB - PURPOSE: Ischemia/reperfusion results in tissue damage, a rapid increase in cytokines and chemokines and inflammatory cell infiltration. Herein we investigated the ability of a selective TLR2/4 antagonist, Sparstolonin B (SsnB), to protect rat cultured left ventricular tissue (LV) slices from hypoxic injury by inhibiting the myocardial inflammatory response independent of inflammatory cell infiltration. METHODS AND RESULTS: Media Lactate dehydrogenase (LDH) levels were measured to reflect hypoxia-induced cytotoxicity and cell injury with and without SsnB. Incubation with SsnB (15 and 30 MUM) significantly reduced by 20 and 40%, respectively, the amount of LDH released from the hypoxic LV slices. TUNEL staining showed that SsnB significantly attenuated the levels of hypoxia induced apoptotic cells from 61.5 +/- 4.0 to 27.0 +/- 2.1 (15 MUM SsnB) and 23.5 +/- 2.2 (30 MUM SsnB) cells/unit area. Similarly, the Periodic Acid-Schiff (PAS) staining of ischemic areas in untreated hypoxic LV slices was increased 17 fold from 0.26+/- 0.09 to 4.41 +/- 0.43%, while in hypoxic slices incubated with 15 and 30 MUM of SsnB, the PAS positive ischemic areas were increased by only 6.4 fold to 1.66 +/- 0.39% and 3.8 fold to 1.00 +/- 0.22%, respectively. Rt-PCR confirmed that MCP1 and IL-6 expression during hypoxia was elevated by 2 and 4 fold, respectively, while their up-regulation was significantly inhibited (i.e., < 0.7 fold increase) by SsnB. CONCLUSION: The selective TLR2/4 antagonist, Sparstolonin B, can substantially protect LV myocardium via its ability to inhibit injury resulting from hypoxic myocardial-generated inflammation. Accordingly SsnB has potential as a therapeutic agent for the attenuation of myocardial ischemia-reperfusion injury. PMID- 25117678 TI - Closing the gap between glia and neuroblast proliferation. AB - Reporting in this issue of Developmental Cell, Speder and Brand (2014) show that gap junctions are required in blood-brain barrier glial cells to reactivate proliferation of quiescent neuroblasts. Gap junctions allow synchronous Ca(2+) waves and control insulin-like protein Dipl6 expression and secretion to trigger neuroblast division. PMID- 25117679 TI - A role for beta3-integrins in linking breast development and cancer. AB - Pregnancy induces a rapid and controlled expansion of mammary stem cells. In this issue of Developmental Cell, Desgrosellier et al. (2014) show that beta3-integrin is required downstream of hormonal signaling and TGFbeta2 to regulate mammary stem cell number and alveolar development specifically during early pregnancy. PMID- 25117680 TI - From blood to brain: the neurogenic niche of the crayfish brain. AB - Adult neurogenic niches are present in both vertebrates and invertebrates. Where do stem cells populating these niches originate, and what are the mechanisms maintaining their self-renewal? In this issue of Developmental Cell, Benton et al. (2014) show that in crayfish, hemolymph-derived cells enter a neurogenic niche to replenish neural progenitors. PMID- 25117681 TI - Control systems of membrane transport at the interface between the endoplasmic reticulum and the Golgi. AB - A fundamental property of cellular processes is to maintain homeostasis despite varying internal and external conditions. Within the membrane transport apparatus, variations in membrane fluxes from the endoplasmic reticulum (ER) to the Golgi complex are balanced by opposite fluxes from the Golgi to the ER to maintain homeostasis between the two organelles. Here we describe a molecular device that balances transport fluxes by integrating transduction cascades with the transport machinery. Specifically, ER-to-Golgi transport activates the KDEL receptor at the Golgi, which triggers a cascade that involves Gs and adenylyl cyclase and phosphodiesterase isoforms and then PKA activation and results in the phosphorylation of transport machinery proteins. This induces retrograde traffic to the ER and balances transport fluxes between the ER and Golgi. Moreover, the KDEL receptor activates CREB1 and other transcription factors that upregulate transport-related genes. Thus, a Golgi-based control system maintains transport homeostasis through both signaling and transcriptional networks. PMID- 25117683 TI - Cells from the immune system generate adult-born neurons in crayfish. AB - Neurogenesis is an ongoing process in the brains of adult decapod crustaceans. However, the first-generation precursors that produce adult-born neurons, which reside in a neurogenic niche, are not self-renewing in crayfish and must be replenished. The source of these neuronal precursors is unknown. Here, we report that adult-born neurons in crayfish can be derived from hemocytes. Following adoptive transfer of 5-ethynyl-2'-deoxyuridine (EdU)-labeled hemocytes, labeled cells populate the neurogenic niche containing the first-generation neuronal precursors. Seven weeks after adoptive transfer, EdU-labeled cells are located in brain clusters 9 and 10 (where adult-born neurons differentiate) and express appropriate neurotransmitters. Moreover, the number of cells composing the neurogenic niche in crayfish is tightly correlated with total hemocyte counts (THCs) and can be manipulated by raising or lowering THC. These studies identify hemocytes as a source of adult-born neurons in crayfish and demonstrate that the immune system is a key contributor to adult neurogenesis. PMID- 25117682 TI - Integrin alphavbeta3 drives slug activation and stemness in the pregnant and neoplastic mammary gland. AB - Although integrin alphavbeta3 is linked to cancer progression, its role in epithelial development is unclear. Here, we show that alphavbeta3 plays a critical role in adult mammary stem cells (MaSCs) during pregnancy. Whereas alphavbeta3 is a luminal progenitor marker in the virgin gland, we noted increased alphavbeta3 expression in MaSCs at midpregnancy. Accordingly, mice lacking alphavbeta3 or expressing a signaling-deficient receptor showed defective mammary gland morphogenesis during pregnancy. This was associated with decreased MaSC expansion, clonogenicity, and expression of Slug, a master regulator of MaSCs. Surprisingly, alphavbeta3-deficient mice displayed normal development of the virgin gland with no effect on luminal progenitors. Transforming growth factor beta2 (TGF-beta2) induced alphavbeta3 expression, enhancing Slug nuclear accumulation and MaSC clonogenicity. In human breast cancer cells, alphavbeta3 was necessary and sufficient for Slug activation, tumorsphere formation, and tumor initiation. Thus, pregnancy-associated MaSCs require a TGF beta2/alphavbeta3/Slug pathway, which may contribute to breast cancer progression and stemness. PMID- 25117684 TI - CLASPs are required for proper microtubule localization of end-binding proteins. AB - Microtubule (MT) plus-end tracking proteins (+TIPs) preferentially localize to MT plus ends. End-binding proteins (EBs) are master regulators of the +TIP complex; however, it is unknown whether EBs are regulated by other +TIPs. Here, we show that cytoplasmic linker-associated proteins (CLASPs) modulate EB localization at MTs. In CLASP-depleted cells, EBs localized along the MT lattice in addition to plus ends. The MT-binding region of CLASP was sufficient for restoring normal EB localization, whereas neither EB-CLASP interactions nor EB tail-binding proteins are involved. In vitro assays revealed that CLASP directly functions to remove EB from MTs. Importantly, this effect occurs specifically during MT polymerization, but not at preformed MTs. Increased GTP-tubulin content within MTs in CLASP depleted cells suggests that CLASPs facilitate GTP hydrolysis to reduce EB lattice binding. Together, these findings suggest that CLASPs influence the MT lattice itself to regulate EB and determine exclusive plus-end localization of EBs in cells. PMID- 25117685 TI - N-cadherin locks left-right asymmetry by ending the leftward movement of Hensen's node cells. AB - The stereotypic left-right (LR) asymmetric distribution of internal organs is due to an asymmetric molecular cascade in the lateral plate mesoderm (LPM) that is originated at the embryonic node. In chicken embryos, molecular asymmetries at Hensen's node are created by leftward cell movements that occur transiently. What terminates these movements, and, moreover, what is the impact of prolonging them on the LR asymmetry cascade? We show that leftward movements last longer when N cadherin function is blocked and cease prematurely when N-cadherin is overexpressed on the right side of the node. The prolonged leftward movements lead to loss of asymmetric expression of fgf8 and nodal at the node region. This originates an abnormal expression of the asymmetric genes cer1 and snai1 in the LPM, resulting in mispositioned hearts. We conclude that N-cadherin stops the leftward cell movements and that this termination is an essential step in the establishment of LR asymmetry. PMID- 25117686 TI - Cisplatin-tethered gold nanospheres for multimodal chemo-radiotherapy of glioblastoma. AB - Glioblastoma multiforme (GBM) remains the most aggressive and challenging brain tumour to treat. We report the first successful chemo-radiotherapy on patient derived treatment resistant GBM cells using a cisplatin-tethered gold nanosphere. After intracellular uptake, the nanosphere effects DNA damage which initiates caspase-mediated apoptosis in those cells. In the presence of radiation, both gold and platinum of cisplatin, serve as high atomic number radiosensitizers leading to the emission of ionizing photoelectrons and Auger electrons. This resulted in enhanced synergy between cisplatin and radiotherapy mediated cytotoxicity, and photo/Auger electron mediated radiosensitisation leading to complete ablation of the tumour cells in an in vitro model system. This study demonstrates the potential of designed nanoparticles to target aggressive cancers in the patient derived cell lines providing a platform to move towards treatment strategies. PMID- 25117687 TI - What would you like to eat, Mr CKD Microbiota? A Mediterranean Diet, please! AB - In this review we elucidate the role of gut microbiota as the plausible missing link between food and health, focusing on chronic kidney disease (CKD). Microbiota, the microbial community harboured in the large intestine, is considered a symbiotic "supplementary organ". It contributes to digestion, mainly through two catabolic pathways: saccharolytic (fermentation) or proteolytic (putrefaction). It also interacts with host influencing immunity, metabolism, and health status. It is believed that a balanced healthy microbiota is primarily saccharolytic and diet has a deep effect on its composition. Mediterranean Diet, UNESCO "Intangible Cultural Heritage of Humanity", prevents cardiovascular and metabolic systemic diseases, thanks to the high supply of fibres and antioxidants. Mediterranean Diet also favours the prevalence of saccharolytic species, while Western Diet promotes the shift towards a proteolytic profile (dysbiosis). Emerging evidences highlight the association between a wide range of diseases and dysbiosis. In CKD a vicious circle exists, in which proteolytic derived microbial metabolites (p-cresol and indoxyl sulphate), represent the main circulating uremic toxins: their accumulation worsens dysbiosis and promotes CKD progression. Gut microbiota shaping through non-pharmacologic nutritional treatments, based on Mediterranean Diet, represents an innovative approach in CKD, potentially restoring microbiota balance, ameliorating CKD conditions and slowing down disease progression. PMID- 25117688 TI - State-dependent neutral delay equations from population dynamics. AB - A novel class of state-dependent delay equations is derived from the balance laws of age-structured population dynamics, assuming that birth rates and death rates, as functions of age, are piece-wise constant and that the length of the juvenile phase depends on the total adult population size. The resulting class of equations includes also neutral delay equations. All these equations are very different from the standard delay equations with state-dependent delay since the balance laws require non-linear correction factors. These equations can be written as systems for two variables consisting of an ordinary differential equation (ODE) and a generalized shift, a form suitable for numerical calculations. It is shown that the neutral equation (and the corresponding ODE- shift system) is a limiting case of a system of two standard delay equations. PMID- 25117690 TI - Radon testing in schools in New York State: a 20-year summary. AB - For nearly 20 years the Department of Health has conducted programs to assist in the measurement and reduction of indoor radon concentrations in 186 schools located primarily in Zone 1 areas of New York State. Although many schools had few or no rooms containing radon above 148 Bq/m(3), some rooms had >740 Bq/m(3) and remediation techniques were utilized to reduce exposure. Short-term radon measurements in the schools showed little correlation to basement and first-floor radon results from single-family homes in the towns. PMID- 25117689 TI - The preventive effect of atorvastatin on atrial fibrillation: a meta-analysis of randomized controlled trials. AB - BACKGROUND: A number of clinical and experimental studies have investigated the effect of atorvastatin on atrial fibrillation (AF), but the results are equivocal. This meta-analysis was performed to evaluate whether atorvastatin can reduce the risk of AF in different populations. METHODS: We searched PubMed, EMBASE and the Cochrane Database for all published studies that examined the effect of atorvastatin therapy on AF up to April 2014. A random effects model was used when there was substantial heterogeneity and a fixed effects model when there was negligible heterogeneity. RESULTS: Eighteen published studies including 9952 patients with sinus rhythm were identified for inclusion in the analysis. Ten studies investigated primary prevention of AF by atorvastatin in patients without AF, seven studies investigated secondary prevention of atorvastatin in patients with AF, and one study investigated mixed populations of patients. Overall, atorvastatin was associated with a decreased risk of AF (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.36-0.70, P < 0.0001). However, subgroup analyses showed that in the primary prevention subgroup (OR 0.55, 95% CI 0.38 0.81, P = 0.002), atorvastatin reduced the risk of new-onset AF in patients after coronary surgery (OR 0.44, 95% CI 0.29-0.68, P = 0.0002), but had no beneficial effect in patients without coronary surgery (OR 0.97, 95% CI 0.59-1.58, P = 0.89); in the secondary prevention subgroup, atorvastatin had no beneficial effect on AF recurrence in patients with electrical cardioversion (EC) (OR 0.57, 95% CI 0.25-1.32, P = 0.19) or without EC (OR 0.38, 95% CI 0.14-1.06, P = 0.06). CONCLUSIONS: This meta-analysis suggests that atorvastatin has an overall protective effect against AF. However, this preventive effect was not seen in all types of AF. Atorvastatin was significantly associated with a decreased risk of new-onset AF in patients after coronary surgery. Moreover, atorvastatin did not prove to exert a significant protective effect against the AF recurrences in both patients who had experienced sinus rhythm restoration by means of EC and those who had obtained cardioversion by means of drug therapy. Thus, further prospective studies are warranted. PMID- 25117691 TI - Interhemispheric plasticity protects the deafferented somatosensory cortex from functional takeover after nerve injury. AB - Functional changes across brain hemispheres have been reported after unilateral cortical or peripheral nerve injury. Interhemispheric callosal connections usually underlie this cortico-cortical plasticity. However, the effect of the altered callosal inputs on local cortical plasticity in the adult brain is not well studied. Ipsilateral functional magnetic resonance imaging (fMRI) activation has been reliably detected in the deafferented barrel cortex (BC) at 2 weeks after unilateral infraorbital denervation (IO) in adult rats. The ipsilateral fMRI signal relies on callosal-mediated interhemispheric plasticity. This form of interhemispheric plasticity provides a good chronic model to study the interaction between callosal inputs and local cortical plasticity. The receptive field of forepaw in the primary somatosensory cortex (S1), which is adjacent to the BC, was mapped with fMRI. The S1 receptive field expanded to take over a portion of the BC in 2 weeks after both ascending inputs and callosal inputs were removed in IO rats with ablated contralateral BC (IO+ablation). This expansion, estimated specifically by fMRI mapping, is significantly larger than what has been observed in the IO rats with intact callosal connectivity, as well as in the rats with sham surgery. This work indicates that altered callosal inputs prevent the functional takeover of the deafferented BC from adjacent cortices and may help preserve the functional identity of the BC. PMID- 25117692 TI - The confounded self-efficacy construct: conceptual analysis and recommendations for future research. AB - Self-efficacy is central to health behaviour theories due to its robust predictive capabilities. In this paper, we present and review evidence for a self efficacy-as-motivation argument in which standard self-efficacy questionnaires - i.e., ratings of whether participants 'can do' the target behaviour - reflect motivation rather than perceived capability. The potential implication is that associations between self-efficacy ratings (particularly those that employ a 'can do' operationalisation) and health-related behaviours simply indicate that people are likely to do what they are motivated to do. There is some empirical evidence for the self-efficacy-as-motivation argument, with three studies demonstrating causal effects of outcome expectancy on subsequent self-efficacy ratings. Three additional studies show that - consistent with the self-efficacy-as-motivation argument - controlling for motivation by adding the phrase 'if you wanted to' to the end of self-efficacy items decreases associations between self-efficacy ratings and motivation. Likewise, a qualitative study using a thought-listing procedure demonstrates that self-efficacy ratings have motivational antecedents. The available evidence suggests that the self-efficacy-as-motivation argument is viable, although more research is needed. Meanwhile, we recommend that researchers look beyond self-efficacy to identify the many and diverse sources of motivation for health-related behaviours. PMID- 25117694 TI - Comparisons in ambulatory physical activity in children from the United Kingdom and Belgium. AB - AIM: This study sought to examine ambulatory physical activity levels in adolescents from the UK and Belgium. METHODS: Following ethics approval, 2760 children (1247 boys, 1513 girls), aged 9-14 years from Belgium (n = 1614) and the UK (n = 1146), wore a pedometer for 4 days including at least 1 weekend day. Body mass index (BMI) was determined from height and mass. RESULTS: A 2 (gender) * 2 (country) way ANCOVA, controlling for age and BMI, revealed a significant country by-gender interaction for steps/day (p = 0.0001). In both Belgium and the UK, boys were more physically active than girls (both p = 0.0001), but the difference between boys and girls was greater for Belgian than UK children. CONCLUSION: These results suggest there are differences in the ambulatory physical activity patterns of children in the UK and Belgium. PMID- 25117693 TI - Structural analysis of N- and O-glycans using ZIC-HILIC/dialysis coupled to NMR detection. AB - Protein glycosylation, an important and complex post-translational modification (PTM), is involved in various biological processes, including the receptor-ligand and cell-cell interaction, and plays a crucial role in many biological functions. However, little is known about the glycan structures of important biological complex samples, and the conventional glycan enrichment strategy (i.e., size exclusion column [SEC] separation) prior to nuclear magnetic resonance (NMR) detection is time-consuming and tedious. In this study, we developed a glycan enrichment strategy that couples Zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) with dialysis to enrich the glycans from the pronase E digests of RNase B, followed by NMR analysis of the glycoconjugate. Our results suggest that the ZIC-HILIC enrichment coupled with dialysis is a simple, fast, and efficient sample preparation approach. The approach was thus applied to analysis of a biological complex sample, the pronase E digest of the secreted proteins from the fungus Aspergillus niger. The NMR spectra revealed that the secreted proteins from A. niger contain both N-linked glycans with a high-mannose core similar to the structure of the glycan from RNase B, and O-linked glycans bearing mannose and glucose with 1->3 and 1->6 linkages. In all, our study provides compelling evidence that ZIC-HILIC separation coupled with dialysis is very effective and accessible in preparing glycans for the downstream NMR analysis, which could greatly facilitate the future NMR-based glycoproteomics research. PMID- 25117695 TI - Detection of Japanese eel endothelial cells-infecting virus (JEECV) in the Japanese eel Anguilla japonica (Temminck & Schlegel), living in natural habitats. PMID- 25117696 TI - Biometry of anterior segment of human eye on both horizontal and vertical meridians during accommodation imaged with extended scan depth optical coherence tomography. AB - PURPOSE: To determine the biometry of anterior segment dimensions of the human eye on both horizontal and vertical meridians with extended scan depth optical coherence tomography (OCT) during accommodation. METHODS: Twenty pre-presbyopic volunteers, aged between 24 and 30, were recruited. The ocular anterior segment of each subject was imaged using an extended scan depth OCT under non- and 3.0 diopters (D) of accommodative demands on both horizontal and vertical meridians. All the images were analyzed to yield the following parameters: pupil diameter (PD), anterior chamber depth (ACD), anterior and posterior surface curvatures of the crystalline lens (ASC and PSC) and the lens thickness (LT). Two consecutive measurements were performed to assess the repeatability and reproducibility of this OCT. They were evaluated by calculating the within-subject standard deviation (SD), a paired t-test, intra-class correlation coefficients (ICC) and the coefficient of repeatability/reproducibility (CoR). RESULTS: There were no significant differences between two consecutive measurements on either horizontal or vertical meridians under both two different accommodative statuses (P>0.05). The ICC for all parameters ranged from 0.775 to 0.998, except for the PSC (0.550) on the horizontal meridian under the non-accommodative status. In addition, the CoR for most of the parameters were excellent (0.004% to 4.89%). In all the parameters, only PD and PSC were found different between the horizontal and vertical meridians under both accommodative statuses (P<0.05). PD, ACD, ASC and PSC under accommodative status were significantly smaller than those under the non-accommodative status, except that the PSC at the vertical meridian did not change. In addition, LT was significantly increased when accommodation. CONCLUSION: The extended scan depth OCT successfully measured the dimensions of the anterior eye during accommodation with good repeatability and reproducibility on both horizontal and vertical meridians. The asymmetry of lens posterior surface and oval-shaped pupil were found during accommodation. PMID- 25117702 TI - In vivo subcellular imaging of tumors in mouse models using a fluorophore conjugated anti-carcinoembryonic antigen antibody in two-photon excitation microscopy. AB - Recently, there has been growing interest in applying fluorescence imaging techniques to the study of various disease processes and complex biological phenomena in vivo. To apply these methods to clinical settings, several groups have developed protocols for fluorescence imaging using antibodies against tumor markers conjugated to fluorescent substances. Although these probes have been useful in macroscopic imaging, the specificity and sensitivity of these methods must be improved to enable them to detect micro-lesions in the early phases of cancer, resulting in better treatment outcomes. To establish a sensitive and highly specific imaging method, we used a fluorophore-conjugated anti carcinoembryonic antigen (CEA) antibody to perform macroscopic and microscopic in vivo imaging of inoculated cancer cells expressing GFP with or without CEA. Macroscopic imaging by fluorescence zoom microscopy revealed that bio-conjugation of Alexa Fluor 594 to the anti-CEA antibody allowed visualization of tumor mass consisting of CEA-expressing human cancer cells, but the background levels were unacceptably high. In contrast, microscopic imaging using a two-photon excitation microscope and the same fluorescent antibody resulted in subcellular-resolution imaging that was more specific and sensitive than conventional imaging using a fluorescence zoom microscope. These results suggest that two-photon excitation microscopy in conjunction with fluorophore-conjugated antibodies could be widely adapted to detection of cancer-specific cell-surface molecules, both in cancer research and in clinical applications. PMID- 25117704 TI - Polo-like kinase 4 inhibition: a strategy for cancer therapy? AB - In this issue of Cancer Cell, Mason and colleagues describe the development of a Polo-like kinase 4 (PLK4) inhibitor (CFI-400945), with promising activity against tumors formed in mice from patient-derived tumor tissue. A clinical trial has been initiated, but questions remain as to whether PLK4 is the only relevant therapeutic target. PMID- 25117703 TI - Dietary squalene increases high density lipoprotein-cholesterol and paraoxonase 1 and decreases oxidative stress in mice. AB - BACKGROUND AND PURPOSE: Squalene, the main hydrocarbon in the unsaponifiable fraction of virgin olive oil, is involved in cholesterol synthesis and it has been reported to own antiatherosclerotic and antiesteatosic effects. However, the squalene's role on lipid plasma parameters and the influence of genotype on this effect need to be addressed. EXPERIMENTAL APPROACHES: Three male mouse models (wild-type, Apoa1- and Apoe- deficient) were fed chow semisynthetic diets enriched in squalene to provide a dose of 1 g/kg during 11 weeks. After this period, their plasma parameters and lipoprotein profiles were analyzed. KEY RESULTS: Squalene administration at a dose of 1 g/kg showed decreased reactive oxygen species in lipoprotein fractions independently of the animal background and caused an specific increase in high density lipoprotein (HDL)-cholesterol levels, accompanied by an increase in phosphatidylcholine and paraoxonase 1 and no changes in apolipoproteins A1 and A4 in wild-type mice. In these mice, the cholesterol increase was due to its esterified form and associated with an increased hepatic expression of Lcat. These effects were not observed in absence of apolipoprotein A1. The increases in HDL- paraoxonase 1 were translated into decreased plasma malondialdehyde levels depending on the presence of Apolipoprotein A1. CONCLUSIONS AND IMPLICATIONS: Dietary squalene promotes changes in HDL- cholesterol and paraoxonase 1 and decreases reactive oxygen species in lipoproteins and plasma malondialdehyde levels, providing new benefits of its intake that might contribute to explain the properties of virgin olive oil, although the phenotype related to apolipoproteins A1 and E may be particularly relevant. PMID- 25117705 TI - YAPping about differentiation therapy in muscle cancer. AB - Overcoming a presumed differentiation block in the childhood muscle cancer embryonal rhabdomyosarcoma is often thought to hold promise as an approach to replace cytotoxic chemotherapy with molecularly-targeted differentiation therapies. In this issue of Cancer Cell, Tremblay and colleagues implicate YAP1 and the Hippo signaling pathway in the maintenance of differentiation-arrested and proliferative phenotypes for embryonal rhabdomyosarcoma. PMID- 25117706 TI - RESICstance is futile-but not in glioblastoma. AB - Genomic alterations that occur early in tumorigenesis represent fundamental diver lesions and are perhaps of highest priority as a means to intervene therapeutically. In this issue of Cancer Cell, Ozawa and colleagues apply an algorithm to identify early events in glioblastoma and validate their findings in a rigorous manner. PMID- 25117707 TI - Inhibit globally, act locally: CDK7 inhibitors in cancer therapy. AB - Cyclin-dependent kinases (CDKs) are involved in temporal control of the cell cycle and transcription and play central roles in cancer development and metastasis. Recently, Kwiatkowski and colleagues identified a novel CDK7-specific inhibitor, THZ1, that hinders proliferation in cancer cell lines and dampens global transcription in T cell leukemia. PMID- 25117708 TI - When deletions gain functions: commandeering epigenetic mechanisms. AB - Recurrent chromosomal deletions in cancer are typically thought to harbor tumor suppressors. In a recent publication in Nature, Northcott and colleagues identify a novel region of structural variation in medulloblastoma that leads to oncogenic activation of GFI1B and GFI1 by repositioning these genes next to super enhancers. PMID- 25117709 TI - Tumor vessel normalization by chloroquine independent of autophagy. AB - Chloroquine (CQ) has been evaluated as an autophagy blocker for cancer treatment, but it is unknown if it acts solely by inhibiting cancer cell autophagy. We report that CQ reduced tumor growth but improved the tumor milieu. By normalizing tumor vessel structure and function and increasing perfusion, CQ reduced hypoxia, cancer cell invasion, and metastasis, while improving chemotherapy delivery and response. Inhibiting autophagy in cancer cells or endothelial cells (ECs) failed to induce such effects. CQ's vessel normalization activity relied mainly on alterations of endosomal Notch1 trafficking and signaling in ECs and was abrogated by Notch1 deletion in ECs in vivo. Thus, autophagy-independent vessel normalization by CQ restrains tumor invasion and metastasis while improving chemotherapy, supporting the use of CQ for anticancer treatment. PMID- 25117710 TI - Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor. AB - Oncoproteins and tumor suppressors antagonistically converge on critical nodes governing neoplastic growth, invasion, and metastasis. We discovered that phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific serine or threonine residues creates binding sites for the COP1 tumor suppressor protein, which is an ubiquitin ligase component, leading to their destruction. In the case of ETS1, however, phosphorylation of a neighboring tyrosine residue by Src family kinases disrupts COP1 binding, thereby stabilizing ETS1. Src-dependent accumulation of ETS1 in breast cancer cells promotes anchorage-independent growth in vitro and tumor growth in vivo. These findings expand the list of potential COP1 substrates to include proteins whose COP1-binding sites are subject to regulatory phosphorylation and provide insights into transformation by Src family kinases. PMID- 25117711 TI - Regulation of p53 by Mdm2 E3 ligase function is dispensable in embryogenesis and development, but essential in response to DNA damage. AB - Mdm2 E3 ubiquitin ligase-mediated p53 degradation is generally accepted as the major mechanism for p53 regulation; nevertheless, the in vivo significance of this function has not been unequivocally established. Here, we have generated an Mdm2(Y487A) knockin mouse; Mdm2(Y487A) mutation inactivates Mdm2 E3 ligase function without affecting its ability to bind its homolog MdmX. Unexpectedly, Mdm2(Y487A/Y487A) mice were viable and developed normally into adulthood. While disruption of Mdm2 E3 ligase function resulted in p53 accumulation, p53 transcriptional activity remained low; however, exposure to sublethal stress resulted in hyperactive p53 and p53-dependent mortality in Mdm2(Y487A/Y487A) mice. These findings reveal a potentially dispensable nature for Mdm2 E3 ligase function in p53 regulation, providing insight that may affect how this pathway is targeted therapeutically. PMID- 25117712 TI - Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models. AB - Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated, and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Therefore, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance. PMID- 25117715 TI - Ethylenediamine-mediated synthesis of Mn3O4 nano-octahedrons and their performance as electrocatalysts for the oxygen evolution reaction. AB - Mn3O4 octahedrons with well-defined facets exhibit enhanced catalytic activity and sensing characteristics, and have attracted considerable attention in recent years. However, current fabrication methods for Mn3O4 octahedrons generally produce particles of micron and sub-micron sizes, and impurities such as MnO2 and Mn2O3 are often found. We present the synthesis of Mn3O4 nano-octahedrons with a pure Mn3O4 phase and size down to 50 nm based on a hydrothermal method using Mn(NO3)2 as the manganese source and ethylenediamine (EDA) as the structure mediating agent. It is found that EDA plays a crucial role in the formation of Mn3O4 nano-octahedrons in regulating both the morphology and the crystal structure of the products. The growth process is proposed to follow a "dissolution-recrystallization" and "capping-molecule assisted growth" mechanism. As electrocatalysts towards the oxygen evolution reaction, the 50 nm Mn3O4 nano octahedrons demonstrate a considerably enhanced activity compared to 160 nm Mn3O4 octahedrons. PMID- 25117713 TI - MYC through miR-17-92 suppresses specific target genes to maintain survival, autonomous proliferation, and a neoplastic state. AB - The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes. PMID- 25117714 TI - Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma. AB - To understand the relationships between the non-GCIMP glioblastoma (GBM) subgroups, we performed mathematical modeling to predict the temporal sequence of driver events during tumorigenesis. The most common order of evolutionary events is 1) chromosome (chr) 7 gain and chr10 loss, followed by 2) CDKN2A loss and/or TP53 mutation, and 3) alterations canonical for specific subtypes. We then developed a computational methodology to identify drivers of broad copy number changes, identifying PDGFA (chr7) and PTEN (chr10) as driving initial nondisjunction events. These predictions were validated using mouse modeling, showing that PDGFA is sufficient to induce proneural-like gliomas and that additional NF1 loss converts proneural to the mesenchymal subtype. Our findings suggest that most non-GCIMP mesenchymal GBMs arise as, and evolve from, a proneural-like precursor. PMID- 25117716 TI - Transcriptional analysis of Volvox photoreceptors suggests the existence of different cell-type specific light-signaling pathways. AB - Photosynthetic organisms, e.g., plants including green algae, use a sophisticated light-sensing system, composed of primary photoreceptors and additional downstream signaling components, to monitor changes in the ambient light environment towards adjust their growth and development. Although a variety of cellular processes, e.g., initiation of cleavage division and final cellular differentiation, have been shown to be light-regulated in the green alga Volvox carteri, little is known about the underlying light perception and signaling pathways. This multicellular alga possesses at least 12 photoreceptors, i.e., one phototropin (VcPhot), four cryptochromes (VcCRYa, VcCRYp, VcCRYd1, and VcCRYd2), and seven members of rhodopsin-like photoreceptors (VR1, VChR1, VChR2, VcHKR1, VcHKR2, VcHKR3, and VcHKR4), which display distinct light-dependent chemical processes based on their protein architectures and associated chromophores. Gene expression analyses could show that the transcript levels of some of the photoreceptor genes (e.g., VChR1 and VcHKR1) accumulate during division cleavages, while others (e.g., VcCRYa, VcCRYp, and VcPhot) accumulate during final cellular differentiation. However, the pattern of transcript accumulation changes when the alga switches to the sexual development. Eight photoreceptor genes, e.g., VcPhot, VcCRYp, and VcHKR1, are highly expressed in the somatic cells, while only the animal-type rhodopsin VR1 was found to be highly expressed in the reproductive cells/embryos during both asexual and sexual life cycles. Moreover, accumulation of VChR1 and VcCRYa transcripts is more sensitive to light and changes in response to more than one light quality. Obviously, different regulatory mechanisms underlying gene expression control transcript accumulation of photoreceptors not only during development, but also in a cell-type specific way and in response to various external signals such as light quality. The transcriptional patterns described in this study show that Volvox photoreceptors are mostly expressed in a cell-type specific manner. This gives reason to believe that cell-type specific light-signaling pathways allow differential regulation of cellular and developmental processes in response to the environmental light cues. PMID- 25117718 TI - Salt restriction in chronic kidney disease: a simple need or a must? AB - Dietary salt restriction is one of the most important non pharmacological intervention in the management of hypertension and cardiovascular complications. In Chronic Kidney Disease (CKD) patients, observational and recent interventional studies investigating the relationship between sodium intake and renal outcomes suggest that low salt diet is warranted in this high risk category of patients. Moreover reducing and maintaining a low salt intake in these patients plays a fundamental role for maximizing the beneficial effect of ACE inhibitors on CKD progression. On the other hand, in hypertensive patients there is experimental evidence indicating that a very low sodium diet (<50 mEq/day) generates a pro inflammatory phenotype characterized by an increase in Procalcitonin and TNF alpha and a reduction in an anti-inflammatory cytokine like Adiponectin. In this brief review the main mechanisms whereby salt intake may determine kidney damage and studies showing that salt restriction may have a beneficial effect in CKD patients will be discussed. PMID- 25117720 TI - Late-onset cauda equina contrast enhancement: a rare magnetic resonance imaging finding in subacute spinal cord infarction. PMID- 25117719 TI - The effect of women's property rights on HIV: a search for quantitative evidence. AB - In recent years, efforts to reduce HIV transmission have begun to incorporate a structural interventions approach, whereby the social, political, and economic environment in which people live is considered an important determinant of individual behaviors. This approach to HIV prevention is reflected in the growing number of programs designed to address insecure or nonexistent property rights for women living in developing countries. Qualitative and anecdotal evidence suggests that property ownership may allow women to mitigate social, economic, and biological effects of HIV for themselves and others through increased food security and income generation. Even so, the relationship between women's property and inheritance rights (WPIR) and HIV transmission behaviors is not well understood. We explored sources of data that could be used to establish quantitative links between WPIR and HIV. Our search for quantitative evidence included (1) a review of peer-reviewed and "gray" literature reporting on quantitative associations between WPIR and HIV, (2) identification and assessment of existing data-sets for their utility in exploring this relationship, and (3) interviews with organizations addressing women's property rights in Kenya and Uganda about the data they collect. We found no quantitative studies linking insecure WPIR to HIV transmission behaviors. Data-sets with relevant variables were scarce, and those with both WPIR and HIV variables could only provide superficial evidence of associations. Organizations addressing WPIR in Kenya and Uganda did not collect data that could shed light on the connection between WPIR and HIV, but the two had data and community networks that could provide a good foundation for a future study that would include the collection of additional information. Collaboration between groups addressing WPIR and HIV transmission could provide the quantitative evidence needed to determine whether and how a WPIR structural intervention could decrease HIV transmission. PMID- 25117717 TI - Advanced biliary tract carcinomas: a retrospective multicenter analysis of first and second-line chemotherapy. AB - BACKGROUND: Gemcitabine/Cisplatin (Gem/CDDP) combination has demonstrated a clear survival advantage over gemcitabine alone and has become a new standard in advanced Biliary Tract Carcinoma (aBTC). However, Gemcitabine/Oxaliplatin (GEMOX) combination and Gemcitabine/Carboplatin (Gem/Carb) combination regimens have shown efficacy in phase II trials and there is no comparative study between different platinum salts.We assessed the efficacy and safety of different platinum-based chemotherapies at first line in aBTC patients. We also analysed the second-line chemotherapy. METHODS: Sixty-four consecutive patients with aBTC diagnosed between 1998 and 2010 were included for analysis. At first line chemotherapy, 44 patients received one day GEMOX regimen (gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 Day 1, every 2 weeks), and 20 patients received Gem/Carb regimen (gemcitabine at 1000 mg/m2 Days 1 and 8 with carboplatin delivered according to an area-under-the-curve (AUC) 5 at day 1, every 3 weeks). At second line, a total of 16 patients received a fluoropyrimidine-based chemotherapy. RESULTS: With GEMOX regimen, median progression-free survival (PFS) was 3.7 months (95%CI, 2.4 to 5) and median overall survival (OS) was 10.5 months (95%CI, 6.4 to14.7). The main toxicity was peripheral neuropathy (20% grade 2 and 7% grade 3). Grade 3/4 haematological toxicities were rare.With Gem/Carb regimen, PFS was 2.5 months (95%CI, 2.1 to 3.7) and OS was 4.8 months (95%CI, 3.7 to 5.8). The main grade 3/4 toxicities were haematological: anaemia (45%), thrombocytopenia (45%), and neutropenia (40%).At second-line, fluoropyrimidine based chemotherapy was feasible in only a fourth of the patients. The median OS was 5.3 months (95%CI, 4.1 to 6.6), and median PFS was 4.0 months (95%CI, 2.6 to 5.5). CONCLUSIONS: One day GEMOX regimen has a favourable toxicity profile and could be an alternative to standard Gem/CDDP regimen, in particular in unfit patients for CDDP.At second-line, selective patients may benefit from fluoropyrimidine-based chemotherapy. PMID- 25117721 TI - Lumbosacral discitis-osteomyelitis after mesh abdominosacrocolpopexy. PMID- 25117722 TI - Temporal specificity of training: intra-day effects on biochemical responses and Olympic-Weightlifting performances. AB - The aim of this study was to investigate the performance of an Olympic Weightlifting session training at three times of the day on the performance related to biochemical responses. Nine weightlifters (21 +/- 0.5 years) performed, in randomised order, on three Olympic-Weightlifting training (snatch, clean and jerk) sessions (08:00 a.m., 02:00 p. m., 06:00 p. m.). Blood samples were collected: before, 3 min and 48 h after each training session. Haematological parameters and markers of muscle injury were assessed. Resting oral temperature and rating of perceived exertion (RPE) were also assessed during each session. ANOVA showed that the performance was better (P < 0.001) at 02:00 p. m. with a less RPE (P < 0.01) compared to the morning and the evening sessions while there was higher (P < 0.05) oral temperature at 06:00 p. m. versus 08:00 a.m. and 02:00 p. m. Muscle damage changed immediately (without significant effect after 48 h) after the training sessions with lower values in the evening compared to the morning. In conclusion, the afternoon training is more effective than morning or evening sessions for weightlifters. Therefore, coaches and weightlifters should be advised to schedule their training session in the afternoon hour. PMID- 25117723 TI - The relationship between hospital volume and mortality in severe sepsis. AB - RATIONALE: Severe sepsis is increasing in incidence and has a high rate of inpatient mortality. Hospitals that treat a larger number of patients with severe sepsis may offer a survival advantage. OBJECTIVES: We sought to assess the effect of severe sepsis case volume on mortality, hypothesizing that higher volume centers would have lower rates of inpatient death. METHODS: We performed a retrospective cohort study over a 7-year period (2004-2010), using a nationally representative sample of hospital admissions, examining the relation between volume, urban location, organ dysfunction, and survival. MEASUREMENTS AND MAIN RESULTS: To identify potential differences in outcomes, hospitals were divided into five categories (<50, 50-99, 100-249, 250-499, and 500+ annual cases) and adjusted mortality was compared by volume. A total of 914,200 patients with severe sepsis were identified over a 7-year period (2004-2010). Overall in hospital mortality was 28.1%. In a fully adjusted model, there was an inverse relationship between severe sepsis case volume and inpatient mortality. Hospitals in the highest volume category had substantially improved survival compared with hospitals with the lowest case volume (adjusted odds ratio, 0.64; 95% confidence interval, 0.60-0.69). In cases of severe sepsis with one reported organ dysfunction, a mortality of 18.9% was found in hospitals with fewer than 50 annual cases compared with 10.4% in hospitals treating 500+ cases (adjusted odds ratio, 0.54; 95% confidence interval, 0.49-0.59). Similar differences were found in patients with up to three total organ dysfunctions. CONCLUSIONS: Patients with severe sepsis treated in hospitals with higher case volumes had improved adjusted outcomes. PMID- 25117724 TI - Early effects of human papillomavirus vaccination in Belgium. AB - Human papillomavirus (HPV) vaccination has been reimbursed in Belgium since 2007 for girls (12-15 years), extended to girls up to 18 years in 2008. This study assesses the trend of HPV 16/18 infections in women less than 25 years of age participating in opportunistic cervical cancer screening. A significant reduction in the prevalence of HPV 16 [relative risk (RR)=0.61, 95% confidence interval=0.39-0.95] and a nonsignificant reduction in HPV 18 (RR=0.65, 95% confidence interval=0.29-1.48) was found in the youngest group (15-19 years). The prevalences in the older age group did not change significantly. These findings show the early effects of HPV vaccination and confirm the effectiveness of immunization in a real-life setting. PMID- 25117725 TI - Nonlinear dose-response relationship between radon exposure and the risk of lung cancer: evidence from a meta-analysis of published observational studies. AB - Although radon exposure (RE) has been confirmed to increase the risk of lung cancer (LC), questions remain about the shape of the dose-response relationship between RE and the risk of LC. We carried out a dose-response meta-analysis to investigate and quantify the potential dose-response association between residential and occupational exposure to radon and the risk of LC. All cohort and case-control studies published in English and Chinese on Embase, PubMed, and China National Knowledge Infrastructure (CNKI) digital databases through November 2013 were identified systematically. We extracted effect measures (relative risk, odds ratio, standardized mortality ratio, standardized incidence ratio, or standardized rate ratio) from individual studies to generate pooled results using meta-analysis approaches. We derived meta-analytic estimates using random-effects models taking into account the correlation between estimates. Restricted cubic splines and generalized least-squares regression methods were used to model a potential curvilinear relationship and to carry out a dose-response meta analysis. Stratified analysis, sensitivity analysis, and assessment of bias were performed in our meta-analysis. Sixty publications fulfilling the inclusion criteria for this meta-analysis were finally included. Occupational RE was associated with LC [risk ratio 1.86, 95% confidence interval (CI)=1.67-2.09; I2=92.2%; 27 prospective studies], for pooled risk estimate of the: standardized mortality ratio [2.00 (95% CI=1.82-2.32)]; standardized incidence ratio [1.45 (95% CI=1.20-1.74)]; relative risk [2.10 (95% CI=1.64-2.69)]. In a subgroup analysis of uranium miners and residents exposed to occupational uranium, the summary risk was 2.23 (95% CI=1.86-2.68) and 1.23 (95% CI=1.05-1.44). The overall meta-analysis showed evidence of a nonlinear association between RE and the risk of LC (P(nonlinearity)<0.014); in addition, the point value of residential radon also improved the results quantitatively, where odds ratios were 1.11 (95% CI=1.07-1.15) and 1.21 (95% CI=1.14-1.29) when the radon concentration was at the point of 100 and 200 Bq/m3 compared with the lowest. For 17 prospective studies with at least three categories of occupational cumulative radon dose, the dose risk model estimated a risk ratio of 1.26 (95% CI=1.21-1.30) for 100 working level months and 1.51 (95% CI=1.38-1.65) for 200 working level months, respectively. The assessment of risk of bias within individual studies and across studies indicated risk that was unlikely to alter these results markedly. This meta-analysis shows a nonlinear dose-response association between environmental RE and the risk of LC. This increased risk is particularly apparent when the cumulative exposure to radon is well beyond that resulting from exposure to the recommended limit concentration for a prolonged period of time. PMID- 25117726 TI - Does decreased meniscal thickness affect surgical outcomes after medial meniscectomy? AB - BACKGROUND: There have been no clinical studies regarding the effect of decreased meniscal thickness on outcomes after meniscectomy. PURPOSE: To examine the postoperative outcomes of partial meniscectomy with or without horizontal resection compared with the outcomes of subtotal meniscectomy and to evaluate the influence of decreased thickness of the medial meniscus on outcomes after partial meniscectomy. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 312 patients who underwent medial meniscectomy were retrospectively reviewed. Patients were divided into 3 groups: group A (n = 84) included patients with partial meniscectomy with vertical resection, group B (n = 140) consisted of those with partial meniscectomy with horizontal resection, and group C (n = 88) included those with subtotal meniscectomy. Clinical function was evaluated by use of the Lysholm knee scoring scale, International Knee Documentation Committee (IKDC) subjective knee evaluation form, and Tapper and Hoover grading system. Radiologic evaluation was performed with the IKDC radiographic assessment scale as well as with measurements of the medial compartment height at the tibiofemoral joint. Preoperative values and postoperative values measured 5 years after operation were assessed. RESULTS: Functional outcomes in group C were inferior to those in groups A and B according to the Lysholm knee score (mean +/- SD for group A = 96.1 +/- 4.7, group B = 94.9 +/- 5.2, group C = 84.8 +/- 11.4; P < .001), IKDC subjective score (group A = 92.1 +/- 6.5, group B = 91.3 +/- 8.8, group C = 81 +/- 11.4; P < .001), and Tapper and Hoover grading system (P = .003). There was no significant difference in scores between groups A and B. With regard to radiologic evaluation, the IKDC radiographic grade for group C was worse than the grades for groups A and B (P < .001); there was no significant difference between groups A and B. However, the postoperative joint space on the affected side was higher for group A (4.7 +/- 0.6 mm) than for groups B (4.3 +/- 0.5 mm; P < .001) and C (3.7 +/- 0.8 mm; P < .001). The joint space was higher in group B than in group C (P < .001). CONCLUSION: Despite joint space narrowing, decreases in meniscal thickness after partial meniscectomy for horizontal tear had no additional adverse effect on 5-year functional and radiographic outcomes compared with conventional partial meniscectomy preserving whole meniscal thickness. In treating horizontal tears of the meniscus, partial meniscectomy with complete resection of the unstable leaf was an effective method in a 5-year follow-up study. PMID- 25117727 TI - Three-dimensional analysis of acromial morphologic characteristics in patients with and without rotator cuff tears using a reconstructed computed tomography model. AB - BACKGROUND: The relationship between rotator cuff tears and acromial shape has yet to be clarified. As a result, the most suitable location for acromioplasty for the treatment of rotator cuff tears is not known. PURPOSE: To determine whether any particular change in acromial shape is significantly associated with the presence of rotator cuff tears. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: From 2007 to 2010, we examined 25 consecutive patients with unilateral full-thickness rotator cuff tears who underwent arthroscopic repair and 17 consecutive patients with adhesive capsulitis but intact rotator cuffs who underwent arthroscopic capsular release. Before surgery, a reconstructed 3 dimensional computed tomography model was used to evaluate the acromial structure. Changes in the shape of the affected scapula were qualitatively evaluated relative to the unaffected, contralateral scapula by use of proximity mapping. Differences in acromial structure between affected and unaffected shoulders were assessed at the anterior, lateral, and medial edges and the inferior surface. The association between rotator cuff tear size and change in acromial structure was also evaluated. RESULTS: Rates of bony projection at the anterior (>2 mm) and lateral (>3 mm) edges of the acromion in patients with rotator cuff tears were significantly greater compared with rates in patients without rotator cuff tears (P < .01). Tear size was not correlated with changes in acromial structure (P = .37-.73). CONCLUSION: Bone spurs at the anterior and lateral edges of the acromion are associated with the presence of full-thickness rotator cuff tears in symptomatic patients. PMID- 25117728 TI - The arthroscopic latarjet procedure for anterior shoulder instability: 5-year minimum follow-up. AB - BACKGROUND: The arthroscopic Latarjet procedure combines the benefits of arthroscopic surgery with the low rate of recurrent instability associated with the Latarjet procedure. Only short-term outcomes after arthroscopic Latarjet procedure have been reported. PURPOSE: To evaluate the rate of recurrent instability and patient outcomes a minimum of 5 years after stabilization performed with the arthroscopic Latarjet procedure. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients who underwent the arthroscopic Latarjet procedure before June 2008 completed a questionnaire to determine whether they had experienced a dislocation, subluxation, or further surgery. The patients also completed the Western Ontario Shoulder Instability Index (WOSI). RESULTS: A total of 62 of 87 patients (64/89 shoulders) were contacted for follow-up. Mean follow up time was 76.4 months (range, 61.2-100.7 months). No patients had reported a dislocation since their surgery. One patient reported having subluxations since the surgery. Thus, 1 patient (1.59%) had recurrent instability after the procedure. The mean +/- standard deviation aggregate WOSI score was 90.6% +/- 9.4%. Mean WOSI domain scores were as follows: Physical Symptoms, 90.1% +/- 8.7%; Sports/Recreation/Work, 90.3% +/- 12.9%; Lifestyle, 93.7% +/- 9.8%; and Emotions, 88.7% +/- 17.3%. CONCLUSION: The rate of recurrent instability after arthroscopic Latarjet procedure is low in this series of patients with a minimum 5-year follow up. Patient outcomes as measured by the WOSI are good. PMID- 25117729 TI - Phase II study of FOLFIRINOX for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. AB - The FOLFIRINOX combination of chemotherapy drugs had not been fully evaluated for Japanese pancreatic cancer patients. Therefore, we carried out a phase II study to examine the efficacy and safety of FOLFIRINOX in chemotherapy-naive Japanese patients with metastatic pancreatic cancer. FOLFIRINOX (i.v. infusion of 85 mg/m(2) oxaliplatin, 180 mg/m(2) irinotecan, and 200 mg/m(2) l-leucovorin, followed by a bolus of 400 mg/m(2) fluorouracil and a 46-h continuous infusion of 2400 mg/m(2) fluorouracil) was given every 2 weeks. The primary endpoint was the response rate. The 36 enrolled patients received a median of eight (range, 1-25) treatment cycles. The response rate was 38.9% (95% confidence interval [CI], 23.1 56.5); median overall survival, 10.7 months (95% CI, 6.9-13.2); and median progression-free survival, 5.6 months (95% CI, 3.0-7.8). Major grade 3 or 4 toxicities included neutropenia (77.8%), febrile neutropenia (22.2%), thrombocytopenia (11.1%), anemia (11.1%), anorexia (11.1%), diarrhea (8.3%), nausea (8.3%), elevated alanine aminotransferase levels (8.3%), and peripheral sensory neuropathy (5.6%). Febrile neutropenia occurred only during the first cycle. There were no treatment-related deaths. FOLFIRINOX can be a standard regimen showing favorable efficacy and acceptable toxicity profile in chemotherapy-naive Japanese patients with metastatic pancreatic cancer. PMID- 25117730 TI - Defined serum- and xeno-free cryopreservation of mesenchymal stem cells. AB - Mesenchymal stem cells (MSCs) have vast potential in cell therapy, and are experimentally used in the clinic. Therefore, it is critical to find a serum- and xeno-free cryopreservation method. The aim of this study was to compare two serum and xeno-free cryoprotectants for MSCs. Adipose tissue MSCs (Ad-MSCs) and bone marrow MSCs (BM-MSCs) were cryopreserved in two cryoprotectants: the defined serum- and xeno-free STEM-CELLBANKERTM (CB) and 10 % dimethyl sulfoxide (DMSO) in a xeno-free serum replacement cell culture medium and compared to non cryopreserved MSCs. MSCs cryopreserved in CB or DMSO had similar morphology and surface marker expression compared to their respective non-cryopreserved MSC. Ad MSCs and BM-MSC in both cryoprotectant media exhibited reduced mean fluorescence intensity (MFI) for CD105, BM-MSCs for CD73 and Ad-MSC increased MFI for HLA class I compared to non-cryopreserved MSCs. Population doubling time of CB cryopreserved and non-cryopreserved Ad-MSCs was similar (38.1 +/- 13.6 and 36.8 +/- 12.1 h), but somewhat higher when cryopreserved in DMSO (42.2 +/- 10.8 h). BM MSCs had higher population doubling time (CB 47.7 +/- 11.4 and DMSO 62.3 +/- 32.9 h respectively, p < 0.05) compared to Ad-MSCs. The viability of Ad-MSCs was significantly higher after cryopreservation in CB compared to DMSO (90.4 +/- 4.5 % vs. 79.9 +/- 3.8 % respectively). Ad-MSCs and BM-MSCs retained their mesodermal differentiation potential when cryopreserved in both cryoprotectants. The characteristics of Ad-MSCs post-thawing are better preserved by CB than by DMSO in serum- and xeno-free medium. Furthermore, Ad-MSCs and BM-MSCs are differently affected by the cryoprotectants, which may have implications for cell therapy. PMID- 25117739 TI - Vanadium complexes with multidentate amine bisphenols. AB - The reaction of VO(acac)2 (acac(-) = acetyl acetonate) with tripodal glycine bisphenol H3L(1) under an ambient atmosphere yields a hexacoordinated vanadium(iv) complex [V(acac)(L(1))] (1). The corresponding reactions with tripodal 2-propanolamine bisphenol H3L(2) and potentially pentadentate ethoxyethanolamine bisphenol H3L(3) lead to the oxidation of the metal centre and formation of mononuclear oxovanadium(v) complexes [VO(L(2))] (2) and [VO(L(3))] (3), respectively. Alternatively, these latter two complexes can be prepared using VOSO4.5H2O or VO(OPr)3 as a precursor. The CV of 1 in an ACN solution shows a reversible one-electron process at E1/2 = +1.18 V, whereas 2 and 3 have an irreversible redox response at -1.6 V and -1.2 V, respectively. Complexes 2 and 3 show moderate activity in the epoxidation of cis-cyclooctene by tert-BuOOH at 50 degrees C. PMID- 25117740 TI - Dialysis exercise team: the way to sustain exercise programs in hemodialysis patients. AB - Patients affected by end-stage renal disease (ESRD) show quite lower physical activity and exercise capacity when compared to healthy individuals. In addition, a sedentary lifestyle is favoured by lack of a specific counseling on exercise implementation in the nephrology care setting. Increasing physical activity level should represent a goal for every dialysis patient care management. Three crucial elements of clinical care may contribute to sustain a hemodialysis exercise program: a) involvement of exercise professionals, b) real commitment of nephrologists and dialysis professionals, c) individual patient adaptation of the exercise program. Dialysis staff have a crucial role to encourage and assist patients during intra-dialysis exercise, but other professionals should be included in the ideal "exercise team" for dialysis patients. Evaluation of general condition, comorbidities (especially cardiovascular), nutritional status and physical exercise capacity are mandatory to propose an exercise program, in either extra-dialysis or intra-dialysis setting. To this aim, nephrologist should lead a team of specialists and professionals including cardiologist, physiotherapist, exercise physiologist, renal dietician and nurse. In this scenario, dialysis nurses play a pivotal role since they guarantee a constant and direct approach. Unfortunately dialysis staff may often lack of information and formation about exercise management while they take care patients during the dialysis session. Building an effective exercise team, promoting the culture of exercise and increasing physical activity levels lead to a more complete and modern clinical care management of ESRD patients. PMID- 25117741 TI - Media reporting of neuroscience depends on timing, topic and newspaper type. AB - The rapid developments in neuroscientific techniques raise high expectations among the general public and therefore warrant close monitoring of the translation to the media and daily-life applications. The need of empirical research into neuroscience communication is emphasized by its susceptibility to evoke misconceptions and polarized beliefs. As the mass media are the main sources of information about (neuro-)science for a majority of the general public, the objective of the current research is to quantify how critically and accurately newspapers report on neuroscience as a function of the timing of publication (within or outside of periods of heightened media attention to neuroscience, termed "news waves"), the topic of the research (e.g. development, health, law) and the newspaper type (quality, popular, free newspapers). The results show that articles published during neuroscience news waves were less neutral and more optimistic, but not different in accuracy. Furthermore, the overall tone and accuracy of articles depended on the topic; for example, articles on development often had an optimistic tone whereas articles on law were often skeptical or balanced, and articles on health care had highest accuracy. Average accuracy was rather low, but articles in quality newspapers were relatively more accurate than in popular and free newspapers. Our results provide specific recommendations for researchers and science communicators, to improve the translation of neuroscience findings through the media: 1) Caution is warranted during periods of heightened attention (news waves), as reporting tends to be more optimistic; 2) Caution is also warranted not to follow topic-related biases in optimism (e.g., development) or skepticism (e.g., law); 3) Researchers should keep in mind that overall accuracy of reporting is low, and especially articles in popular and free newspapers provide a minimal amount of details. This indicates that researchers themselves may need to be more active in preventing misconceptions to arise. PMID- 25117742 TI - Pressure response of amide one-bond J-couplings in model peptides and proteins. AB - The pressure dependence of the one-bond indirect spin-spin coupling constants (1)J(N-H) was studied in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (with Xxx being one of the 20 proteinogenic amino acids). The response of the (1)J(N-H) coupling constants is amino acid type specific, with an average increase of its magnitude by 0.6 Hz at 200 MPa. The variance of the pressure response is rather large, the largest pressure effect is observed for asparagine where the coupling constant becomes more negative by -2.9 Hz at 200 MPa. The size of the J-coupling constant at high pressure is positively correlated with its low pressure value and the beta-propensity, and negatively correlated with the amide proton shift and the first order nitrogen pressure coefficient and the electrostatic solvation free energy. PMID- 25117743 TI - Volumetric MR-guided high-intensity focused ultrasound versus uterine artery embolisation for treatment of symptomatic uterine fibroids: comparison of symptom improvement and reintervention rates. AB - PURPOSE: To compare the effectiveness of magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) with that of uterine artery embolisation (UAE) for treatment of uterine fibroids. METHODS: Between January 2010 and January 2013, 51 women with symptomatic uterine fibroids underwent MR-HIFU. Follow-up and MR imaging were compared to 68 women treated with UAE, who fulfilled eligibility criteria for MR-HIFU - e.g., size (<= 12 cm) and number (<= 5) of fibroids. We compared median symptom severity (tSSS), total health-realted quality of life (HRQoL) scores, and reintervention rates. The adjusted effect on symptom relief and HRQoL improvement was calculated using multivariable linear regression. Cox regression was applied to calculate the adjusted risk of reintervention between both treatments. RESULTS: Median tSSS improved significantly from baseline to three-month follow-up (P < 0.001) for both MR-HIFU (53.1 (IQR [40.6-68.8]) to 34.4 (IQR [21.9-46.9]) and UAE (65.3 (IQR [56.3-74.2]) to 21.9 (IQR [9.4-34.4]). In addition, significantly better HRQoL scores were observed after three months (P < 0.001). However, in multivariate analysis, UAE had a stronger effect on symptom relief and HRQoL improvement than MR-HIFU (P < 0.001). Patients treated with MR-HIFU had a 7.1 (95 % CI [2.00-25.3]; P = 0.002) times higher risk of reintervention within 12 months (18/51 vs. 3/68). CONCLUSION: Both MR-HIFU and UAE result in significant symptom relief related to uterine fibroids. However, MR HIFU is associated with a higher risk of reintervention. KEY POINTS: * This study compared outcomes between volumetric MR-HIFU and UAE for uterine fibroids. * Both MR-HIFU and UAE result in significant symptom relief and quality of life improvement. * UAE had a stronger positive effect on the clinical outcomes. * Reintervention rate after MR-HIFU ablation was significantly higher than after UAE. PMID- 25117744 TI - The clinical utility of reduced-distortion readout-segmented echo-planar imaging in the head and neck region: initial experience. AB - OBJECTIVES: To evaluate whether readout-segmented echo-planar imaging (RS-EPI) diffusion weighted image (DWI) can diminish image distortion in the head and neck area, compared with single-shot (SS)-EPI DWI. METHODS: We conducted phantom and patient studies using 3 T magnetic resonance imaging (MRI) with a 16-channel coil. For the phantom study, we evaluated distortion and signal homogeneity in gel phantoms. For the patient study, 29 consecutive patients with clinically suspicious parotid lesions were prospectively enrolled. RS-EPI and SS-EPI DWI were evaluated by two independent readers for identification of organ/lesion and distortion, using semiquantitative scales and quantitative scores. Apparent diffusion coefficient (ADC) values and contrast-noise ratios of parotid tumours (if present; n = 15) were also compared. RESULTS: The phantom experiments showed that RS-EPI provided less distorted and more homogeneous ADC maps than SS-EPI. In the patient study, RS-EPI was found to provide significantly less distortion in almost all organs/lesions (p < 0.05), according to both semiquantitative scales and quantitative scores. There was no significant difference in ADC values and contrast-noise ratios between the two DWI techniques. CONCLUSIONS: The distortion in DWI was significantly reduced with RS-EPI in both phantom and patient studies. The RS-EPI technique provided more homogenous images than SS-EPI, and can potentially offer higher image quality in the head and neck area. KEY POINTS: The distortion in DWI is significantly reduced with RS-EPI compared with SS-EPI. Structures in the head and neck were identified more clearly using RS-EPI. No significant difference in ADC values was found between the techniques. PMID- 25117745 TI - Impact of contrast-enhanced ultrasound in the study of hepatic artery hypoperfusion shortly after liver transplantation: contribution to the diagnosis of artery steal syndrome. AB - OBJECTIVE: To assess the value of contrast-enhanced ultrasound (CEUS) in the absence of hepatic artery signal on Doppler ultrasound (DUS) in the immediate postoperative period after liver transplant. METHODS: This prospective study included 675 consecutive liver transplants. Patients without hepatic artery signal by DUS within 8 days post-transplant were studied with CEUS. If it remained undetectable, a thrombosis was suspected. In patent hepatic artery, a DUS was performed immediately after CEUS; if low resistance flow was detected, an arteriography was indicated. Patients with high resistance waveform underwent DUS+/CEUS follow-up. Arteriography was indicated when abnormal flow persisted for more than 5 days or liver dysfunction appeared. RESULTS: Thirty-four patients were studied with CEUS. In 11 patients CEUS correctly diagnosed hepatic artery thrombosis. In two out of 23 non-occluded arteries, a low resistance flow lead to a diagnosis of stenosis/proximal thrombosis. Twenty-one patients had absence of diastolic flow, which normalized in the follow-up in 13 patients. In the remaining eight patients, splenic artery steal syndrome (ASS) was diagnosed. CONCLUSIONS: CEUS allows us to avoid invasive tests in the diagnostic work-up shortly after liver transplant. It identifies the hepatic artery thrombosis and points to a diagnosis of ASS. KEY POINTS: * CEUS is useful in the diagnostic work up shortly after liver transplant * CEUS identifies the hepatic artery thrombosis with reliability * There is little information about DUS and CEUS findings in the ASS * DUS and CEUS offer functional information useful in the diagnosis of ASS. PMID- 25117746 TI - Does tumoral (111)In-ibritumomab accumulation correlate with therapeutic effect and outcome in relapsed or refractory low-grade B-cell lymphoma patients undergoing (90)Y-ibritumomab radioimmunotherapy? AB - OBJECTIVES: The aim of this study was to determine whether tumoral (111)In ibritumomab accumulation on pre-treatment imaging correlates with therapeutic responses and progression-free survival (PFS) in patients with non-Hodgkin's lymphoma (NHL) undergoing (90)Y-ibritumomab radioimmunotherapy (RIT). METHODS: This was a retrospective study of 39 patients with low-grade B-cell NHL treated with RIT. We classified the patients into positive and negative groups according to the presence or absence of tumoral (111)In-ibritumomab accumulation on pre treatment (111)In-ibritumomab examinations. We then determined the correlation between the (111)In-ibritumomab imaging findings and the patients' therapeutic responses and PFS. RESULTS: Tumoral (111)In-ibritumomab accumulation was positive in 64.1% and negative in 35.9% of the patients. The (111)In-positive patients had a significantly higher overall response rate (ORR) compared to the (111)In negative patients (100.0% vs. 78.6%, p = 0.02). The (111)In-negative patients with advanced disease (stages III/IV) had a significantly lower ORR (40%) and a significantly higher rate of progressive disease (40.0%) compared to those of the (111)In-negative patients with limited disease (stages I/II) (100% and 0%, p = 0.009 each). However, these two groups had similar 2-year PFS rates (65.0% vs. 50.0%, p = 0.80). CONCLUSIONS: (111)In-ibritumomab imaging findings seem to correlate with ORR and the progressive disease rate after RIT, but not with PFS. KEY POINTS: All 39 NHL patients had tumoral accumulation on pretreatment FDG PET/CT. 64.1% of NHL patients had tumoral accumulation on a pretreatment (111) In ibritumomab examination. (90) Y-ibritumomab RIT resulted in high overall response and complete remission rates. (111) In-ibritumomab avidity of lymphoma lesions could predict a strong therapeutic effect. (111) In-ibritumomab imaging findings did not correlate with progression-free survival. PMID- 25117747 TI - Multiparametric magnetic resonance imaging for the differentiation of low and high grade clear cell renal carcinoma. AB - PURPOSE: To retrospectively evaluate the ability of magnetic resonance (MR) imaging to differentiate low from high Fuhrman grade renal cell carcinoma (RCC). MATERIALS AND METHODS: MR images from 80 consecutive pathologically proven RCC (57 clear cell, 16 papillary and 7 chromophobe) were evaluated. Double-echo chemical shift, dynamic contrast-enhanced T1- and T2-weighted images and apparent diffusion coefficient (ADC) maps were reviewed independently. Signal intensity index (SII), tumour-to-spleen SI ratio (TSR), ADC ratio, wash-in (WiI) and wash out indices (WoI) between different phases were calculated and compared to pathological grade and size. The Fuhrman scoring system was used. Low grade (score <= 2) and high grade (score >= 3) tumours were compared using univariate and multivariate analyses. RESULTS: No associations between grade and imaging factors were found for papillary and chromophobe RCCs. For clear cell RCCs, there was a significant association between the grade and parenchymal WiI (WiI2) (P = 0.02) or ADCr (P = 0.03). A significant association between tumour grade and size (P = 0.01), WiI2 (P = 0.02) and ADCr (P = 0.05) remained in multivariate analysis. CONCLUSIONS: Multiparametric MRI can be used to accurately differentiate low Fuhrman grade clear cell RCC from high grade. High Fuhrman grade (>= 3) RCCs were larger, had lower parenchymal wash-in indices and lower ADC ratios than low grade. KEY POINTS: * Fuhrman grade of clear cell RCC can be differentiated with multiparametric MR imaging. * Fuhrman grade significantly differed for size, parenchymal wash-in index and ADC ratio. * No significant associations were found for papillary and chromophobe renal cell carcinoma. PMID- 25117748 TI - Interleukin-6 concentrations in the urine and dipstick analyses were related to bacteriuria but not symptoms in the elderly: a cross sectional study of 421 nursing home residents. AB - BACKGROUND: Up to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. A complementary test to discriminate between symptomatic urinary tract infections (UTI) and ABU is needed, as diagnostic uncertainty is likely to generate significant antibiotic overtreatment. Previous studies indicate that Interleukin 6 (IL-6) in the urine might be suitable as such a test. The aim of this study was to investigate the association between laboratory findings of bacteriuria, IL-6 in the urine, dipstick urinalysis and newly onset symptoms among residents of nursing homes. METHODS: In this cross sectional study, voided urine specimens for culture, urine dipstick and IL-6 analyses were collected from all residents capable of providing a voided urine sample, regardless of the presence of symptoms. Urine specimens and symptom forms were provided from 421 residents of 22 nursing homes. The following new or increased nonspecific symptoms occurring during the previous month were registered; fatigue, restlessness, confusion, aggressiveness, loss of appetite, frequent falls and not being herself/himself, as well as symptoms from the urinary tract; dysuria, urinary urgency and frequency. RESULTS: Recent onset of nonspecific symptoms was common among elderly residents of nursing homes (85/421). Urine cultures were positive in 32% (135/421), Escherichia coli was by far the most common bacterial finding. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Residents with positive urine cultures had higher concentrations of IL-6 in the urine (p < 0.001). However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms. CONCLUSIONS: Nonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. This study could not establish any clinical value of using dipstick urinalysis or IL-6 in the urine to verify if bacteriuria was linked to nonspecific symptoms. PMID- 25117749 TI - Vulnerabilities faced by the children of sex workers in two Mexico-US border cities: a retrospective study on sexual violence, substance use and HIV risk. AB - Most studies of female sex workers (FSWs) conducted in the Mexico-US border region have focused on individual HIV risk, centered on sexual behaviors and substance abuse patterns. Little attention has been drawn to the reality that sex workers are often parents whose children potentially face vulnerabilities unique to their family situation. The objective of the present study was to identify the vulnerabilities faced by the children of FSWs in two Mexican-US border cities. From 2008 to 2010, 628 FSW-injection drug users underwent interviewer administered surveys and HIV/STI testing. Approximately one in five participants (20%) reported having a parent involved in sex work and majority referred it was their mother (88%). Close to one-third of participants (31%) reported first injecting drugs <18 years of age, and 33% reported they began working regularly as a prostitute <18 years of age. First drinking alcohol <18 years old (AOR = 1.87, 95%CI: 1.13-3.08), lifetime cocaine use (AOR = 1.76, 95%CI: 1.09-2.84), ever being forced or coerced into non-consensual sex as a minor (<18 years of age; AOR = 1.54, 95%CI: 1.01-2.35), and injecting drugs with used syringes in the prior month (AOR = 1.63, 95%CI: 1.07-2.49) were the factors associated with having had a parent involved in sex work. These findings begin to lay the groundwork for understanding the potential vulnerabilities faced by the children of sex workers. Understanding these potential needs is necessary for creating relevant, evidence-based interventions focused on supporting these women. PMID- 25117750 TI - Progression of cardio-metabolic risk factors in subjects born small and large for gestational age. AB - BACKGROUND: Subjects born small (SGA) and large (LGA) for gestational age have an increased risk of cardio-metabolic alterations already during prepuberty. Nevertheless, the progression of their cardio-metabolic profile from childhood to adolescence has not been fully explored. Our aim was to assess potential changes in the cardio-metabolic profile from childhood to adolescence in subjects born SGA and LGA compared to those born appropriate (AGA) for gestational age. METHODS: This longitudinal study included 35 AGA, 24 SGA and 31 LGA subjects evaluated during childhood (mean age (+/- SD) 8.4 +/- 1.4 yr) and then re assessed during adolescence (mean age 13.3 +/- 1.8 yr). BMI, blood pressure, insulin resistance (fasting insulin, HOMA-IR) and lipids were assessed. A cardio metabolic risk z-score was applied and this consisted in calculating the sum of sex-specific z-scores for BMI, blood pressure, HOMA-IR, triglycerides and triglycerides:high-density lipoprotein cholesterol ratio. RESULTS: Fasting insulin and HOMA-IR were higher in SGA and LGA than AGA subjects both during childhood (all P<0.01) and adolescence (all P<0.01). Similarly, the clustered cardio-metabolic risk score was higher in SGA and LGA than AGA children (both P<0.05), and these differences among groups increased during adolescence (both P<0.05). Of note, a progression of the clustered cardio-metabolic risk score was observed from childhood to adolescence within SGA and within LGA subjects (both P<0.05). CONCLUSIONS: SGA and LGA subjects showed an adverse cardio-metabolic profile during childhood when compared to AGA peers, with a worsening of this profile during adolescence. These findings indicate an overtime progression of insulin resistance and overall estimated cardiovascular risk from childhood to adolescence in SGA and LGA populations. PMID- 25117751 TI - Classification of CT pulmonary angiography reports by presence, chronicity, and location of pulmonary embolism with natural language processing. AB - In this paper we describe an efficient tool based on natural language processing for classifying the detail state of pulmonary embolism (PE) recorded in CT pulmonary angiography reports. The classification tasks include: PE present vs. absent, acute PE vs. others, central PE vs. others, and subsegmental PE vs. others. Statistical learning algorithms were trained with features extracted using the NLP tool and gold standard labels obtained via chart review from two radiologists. The areas under the receiver operating characteristic curves (AUC) for the four tasks were 0.998, 0.945, 0.987, and 0.986, respectively. We compared our classifiers with bag-of-words Naive Bayes classifiers, a standard text mining technology, which gave AUC 0.942, 0.765, 0.766, and 0.712, respectively. PMID- 25117752 TI - Seasonal variations of vitamin D concentrations in pregnant women and neonates in Slovenia. AB - OBJECTIVE: While foreign research shows a high prevalence of vitamin D deficiency in pregnant women and consequently in neonates, we do not have any data on vitamin D concentration in these risk groups for Slovenia. We performed a prospective study to evaluate vitamin D concentration in pregnant women and neonates in Maribor region. STUDY DESIGN: We determined 25-hydroxy-vitamin D concentration from blood samples taken before delivery from 100 pregnant women who gave birth in Maribor University Clinical Centre in September and December 2013, respectively, and from the cord blood of their neonates. We collected data on nutrition and sun exposure during pregnancy. We calculated the vitamin D concentrations in pregnant women and neonates according to season of birth and use of nutrition supplements, determined the vitamin D levels in some pregnancy complications and checked the correlation of maternal and neonatal vitamin D concentrations. RESULTS: The average vitamin D concentration in the September group was 54.3+/-25.2nmol/L, and in the December group 33.3+/-18.6nmol/L (p<0.001). Optimal vitamin D concentration (>80nmol/L) was reached by 12.0% of pregnant women in September and by only 2.0% in December. Women who took nutrition supplements containing vitamin D during pregnancy had significantly higher vitamin D levels than those who did not (September 68.9+/-27.0nmol/L vs. 46.5+/-20.3nmol/L, p<0.001; December 38.7+/-17.9nmol/L vs. 30.2+/-18.4nmol/L, p=0.028). Neonates had higher average levels of vitamin D than their mothers but there was a good correlation between maternal and neonatal vitamin D values. CONCLUSION: Vitamin D deficiency is very common in pregnant women in Slovenia as well, especially in winter and in those women who do not take nutrition supplements containing vitamin D. PMID- 25117753 TI - Fall in genital warts diagnoses in the general and indigenous Australian population following implementation of a national human papillomavirus vaccination program: analysis of routinely collected national hospital data. AB - BACKGROUND: Human papillomavirus (HPV) vaccination targeting females aged 12-13 years commenced in Australia in 2007, with catch-up vaccination of females aged 13-26 years continuing to 2009. Whole-population analyses, including effects on the Indigenous population, have not previously been reported. METHODS: All hospital admissions between 1999-2011 involving a diagnosis of genital warts were obtained from a comprehensive national database. We compared the age-specific rates before to those after implementation of the vaccination program, according to sex and other characteristics. RESULTS: Admission rates decreased from mid 2007 in females aged 12-17 years (annual decline, 44.1% [95% confidence interval {CI}, 35.4%-51.6%]) and from mid-2008 in females and males aged 18-26 years (annual declines, 31.8% [95% CI, 28.4%-35.2%] and 14.0% [95% CI, 5.1%-22.1%], respectively). The overall reductions from 2006-2007 to 2010-2011 were 89.9% (95% CI, 84.4%-93.4%) for females aged 12-17 years, 72.7% (95% CI, 67.0%-77.5%) for females aged 18-26 years, and 38.3% (95% CI, 27.7%-47.2%) for males aged 18-26 years. Compared with the average annual number before program implementation, about 1000 fewer hospital admissions involved a warts diagnosis during 2010-2011. Reductions after program implementation were similar for Indigenous (86.7% [95% CI, 76.0-92.7]) and non-Indigenous (76.1% [95% CI, 71.6%-79.9%]) females aged 15 24 years (P(heterogeneity) = .08). CONCLUSIONS: National population-based hospital data confirm previous clinic-based reports of a marked decline in genital warts diagnoses among young people in Australia after program implementation, including indirect benefits to males. The impact of HPV vaccination appears to be similar in young Indigenous and non-Indigenous females. PMID- 25117754 TI - Measles outbreak response among adolescent and adult Somali refugees displaced by famine in Kenya and Ethiopia, 2011. AB - BACKGROUND: The refugee complexes of Dadaab, Kenya, and Dollo-Ado, Ethiopia, experienced measles outbreaks during June-November 2011, following a large influx of refugees from Somalia. METHODS: Line-lists from health facilities were used to describe the outbreak in terms of age, sex, vaccination status, arrival date, attack rates (ARs), and case fatality ratios (CFRs) for each camp. Vaccination data and coverage surveys were reviewed. RESULTS: In Dadaab, 1370 measles cases and 32 deaths (CFR, 2.3%) were reported. A total of 821 cases (60.1%) were aged >=15 years, 906 (82.1%) arrived to the camps in 2011, and 1027 (79.6%) were unvaccinated. Camp-specific ARs ranged from 212 to 506 cases per 100 000 people. In Dollo-Ado, 407 cases and 23 deaths (CFR, 5.7%) were reported. Adults aged >=15 years represented 178 cases (43.7%) and 6 deaths (26.0%). Camp-specific ARs ranged from 21 to 1100 cases per 100 000 people. Immunization activities that were part of the outbreak responses initially targeted children aged 6 months to 14 years and were later expanded to include individuals up to 30 years of age. CONCLUSIONS: The target age group for outbreak response-associated immunization activities at the start of the outbreaks was inconsistent with the numbers of cases among unvaccinated adolescents and adults in the new population. In displacement of populations from areas affected by measles outbreaks, health authorities should consider vaccinating adults in routine and outbreak response activities. PMID- 25117755 TI - In vivo prediction of tuberculosis-associated cavity formation in rabbits. AB - The presence of cavitary lesions in patients with tuberculosis poses a significant clinical concern due to the risk of infectivity and the risk of antibiotic treatment failure. We describe 2 algorithms that use noninvasive positron emission tomography (PET) and computed tomography (CT) to predict the development of cavitary lesions in rabbits. Analysis of the PET region of interest predicted cavitary disease with 100% sensitivity and 76% specificity, and analysis of the CT region of interest predicted cavitary disease with 83.3% sensitivity and 76.9% specificity. Our results show that restricting our analysis to regions with high [(18)F]-fluorodeoxyglucose uptake provided the best combination of sensitivity and specificity. PMID- 25117756 TI - Disease-specific T-helper cell polarizing function of lesional dendritic cells in different types of chronic rhinosinusitis with nasal polyps. AB - RATIONALE: Although eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) exhibit distinct T-helper (Th) responses, the underlying mechanisms remain unclear. OBJECTIVES: To clarify the phenotypes and Th-cell polarizing functions of dendritic cells (DCs) in different types of CRSwNP. METHODS: DC subsets, their surface phenotypes, and Th-cell subsets were studied by means of immunohistochemistry and flow cytometry. The sorted lesional DCs were activated or cultured with autologous naive CD4(+) T cells, and cytokine production was determined by ELISA. Thymic stromal lymphopoietin and osteopontin expression were detected by means of reverse-transcriptase polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Although elevated local Th1 and Th17 cells were noted in both eosinophilic and noneosinophilic CRSwNP, increased Th2 cells were found only in eosinophilic CRSwNP. Increased numbers of myeloid DCs, plasmacytoid DCs, and their activated subsets were found in both types of CRSwNP, but only myeloid DCs and plasmacytoid DCs from eosinophilic CRSwNP demonstrated an up-regulation of OX40 ligand (OX40L) and programmed death ligand 1(PD-L1) expression. Lesional DCs from both types of CRSwNP produced enhanced levels of IL 12, IL-6, and transforming growth factor-beta, and induced increased Th1 and Th17 responses; in contrast, only DCs from eosinophilic CRSwNP induced obviously enhanced Th2 responses, when cocultured with naive CD4(+) T cells. Blockade of OX40L and PD-L1 on lesional DCs from eosinophilic CRSwNP suppressed Th2 responses, but promoted Th1 responses in DC-T cell coculture. CONCLUSIONS: Distinct subsets of lesional DCs were found in eosinophilic and noneosinophilic CRSwNP, where OX40L/PD-L1(+) lesional DCs in eosinophilic CRSwNP could prime Th2 cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic CRSwNP primarily induced Th1/Th17 cells. PMID- 25117758 TI - Chronic kidney disease (CKD) as a systemic disease: whole body autoregulation and inter-organ cross-talk. AB - The inter-organ cross-talk and the functional integration of organ systems is an exceedingly complex process which until now has been investigated with a reductionist approach. CKD perturbs the inter-organ cross-talk and demands central resetting of autonomic (nervous) control of organ systems. Due to limitations inherent to the reductionist approach, we currently identify CKD related pseudo-syndromes and largely fail at describing the complex systemic inter-relationships set into motion by renal damage and renal dysfunction. A mature technology for a system-analysis approach to physiology and pathophysiology of CKD now exists. System biology will allow in depth understanding of complex diseases like CKD and will set the stage for predictive, preventive and personalized medicine, a long-standing dream of doctors and patients alike. PMID- 25117757 TI - PD-1 expression on peripheral blood T-cell subsets correlates with prognosis in non-small cell lung cancer. AB - PD-1 expression in peripheral blood T-cells has been reported in several kinds of cancers, including lung cancer. However, the relationship between PD-1 expression in peripheral blood T-cells and prognosis after treatment with a cancer vaccine has not been reported. To elucidate this relationship, we analyzed PD-1 expression in the peripheral blood T-cells of patients with non-small cell lung cancer. The blood samples used in this study were obtained from patients enrolled in phase II clinical trials of a personalized peptide vaccine. Seventy-eight samples obtained before and after a single vaccination cycle (consisting of six or eight doses) were subjected to the analysis. PD-1 was expressed on lymphocytes in the majority of samples. The relative contents of PD1(+) CD4(+) T-cells against total lymphocytes before and after the vaccination cycle correlated with overall survival (OS) with a high degree of statistical significance (P < 0.0001 and P = 0.0014). A decrease in PD-1(+) CD8(+) T-cells after one cycle of vaccination also correlated with longer OS (P = 0.032). The IgG response to the non-vaccinated peptides suggested that the epitope spreading seemed to occur more frequently in high-PD-1(+) CD4(+) T-cell groups. Enrichment of CD45RA(-) CCR7(-) effector-memory phenotype cells in PD-1(+) T-cells in PBMCs was also shown. These results suggest that PD-1 expression on the peripheral blood T-cell subsets can become a new prognostic marker in non-small cell lung cancer patients treated with personalized peptide vaccination. PMID- 25117759 TI - Physical and mental decline and yet rather happy? A study of Danes aged 45 and older. AB - OBJECTIVES: Little is known about whether the feeling of happiness follows the age-related decline in physical and mental functioning. The objective of this study was to analyze differences with age in physical and mental functions and in the feeling of happiness among Danes aged 45 years and older. METHOD: Three Danish population-based surveys including 11,307 participants aged 45+ years, of whom 2411 were in the age group of 90+, were conducted in the period 1995-2001. The participation rate in the three surveys was between 63% and 82% and the same design and the same instrument were used. Self-reported mobility, a cognitive composite score, and a depression symptomatology score including a question about happiness were assessed. T-score metric was used to compare across domains and age groups. RESULTS: Overall, successively older age groups performed worse than the youngest age group (45-49 years), and the estimated linear decline was greater after age 70 than before age 70. For example, when comparing the oldest age group (90+ years) with the youngest, the T-score differences were found to be the largest for the mobility score (men: 40.2, women: 41.4), followed by the cognitive function (men: 22.0, women: 24.9), and the total depression symptomatology score (men: 15.5, women: 17.4). Conversely, the T-score difference in happiness was small (men: 5.6, women: 6.0). CONCLUSION: Despite markedly poorer physical and mental functions with increasing age, in this Danish sample age did not seem to affect happiness to a similarly notable extent, although, in this study, cohort and age effects cannot be disentangled. PMID- 25117762 TI - Dinuclear Cu(II) complexes based on two flexible Schiff-base ligands and one unusual in situ formed diphenolate 2,6-piperidin-4-one derivative. AB - A dinuclear Cu(ii) complex [Cu2(L3)2].2H2O, having an unprecedented in situ formed diphenolate 2,6-piperidin-4-one derived ligand produced from the flexible Schiff-base ligand HL1, can be yielded as a side product in the presence of Cu(OAc)2.H2O-NH3.H2O dissolved in methanol and acetone in addition to the expected dinuclear Cu(ii) complex [Cu2(L1)4]. PMID- 25117760 TI - Estimating the number of hand, foot and mouth disease amongst children aged under five in Beijing during 2012, based on a telephone survey of healthcare seeking behavior. AB - BACKGROUND: Over the last decade, increases in the number of outbreaks of hand, foot and mouth disease (HFMD) have shifted the disease into the public health spotlight in China. Children under the age of five years are particularly susceptible, with fatalities recorded. However, estimating the burden of HFMD has been difficult to conduct to date. METHODS: In 2012, a cross-sectional survey of healthcare-seeking behaviour for HFMD was undertaken, using computer assisted telephone interviewing (CATI) technology. Sample of telephone numbers was obtained from the Beijing Immunization Information System. Respondents were parents or guardians of children under the age of five. Multiplier model was used to estimate the number of HFMD case, following the telephone survey of healthcare seeking behavior. The number of laboratory-confirmed cases was also estimated based on the monthly positive rate of each subtype of virus causing HFMD. The age specific case fatality rate (CFR) was calculated based on the ratio of reported deaths to the estimated number of cases. RESULTS: For children under five, the consultation rate of parent-defined cases was estimated at 77.8% ((95% CI = [75.2, 80.4]). Parents or legal guardians of children aged between two and four years were more likely to seek healthcare than those of children aged less than two years. For children under the age of five, we estimated that there were 40,165 (95% CI = [38,471, 41,974]) HFMD cases, with an incidence rate of 5.6%, and 22,166 (95% CI = [21,150, 23,295]) laboratory-confirmed cases in Beijing during 2012. The overall CFR was estimated at 10 deaths per 100,000 cases, while for children aged less than two years it was 15.6 deaths per 100,000 cases. CONCLUSIONS: Given the public health impact of HFMD in China, control measures need to be prioritized for children < 2 years, due to the higher CFR in this age group. Sentinel surveillance approaches could be used to monitor trends and the impact of control measures. PMID- 25117761 TI - Comparison of long-term clinical outcomes between sirolimus- and paclitaxel eluting stents in real-world clinical practice. AB - Advances in percutaneous coronary intervention (PCI) have improved the outcomes of patients with coronary artery diseases. The advent of drug-eluting stents (DES) has dramatically reduced the rate of revascularization. The first generation DES has yielded the main role of PCI to the second-generation DES; however, many patients had been implanted with the first-generation DES, sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Therefore, it is of importance to detect the long-term clinical outcomes in patients who underwent PCI with SES or PES. We analyzed data from our PCI cohort who underwent PCI with first-generation DES at Juntendo University Hospital between August 2004 and June 2010. The index procedure was analyzed when patients underwent multiple PCIs. Patients who were implanted with both SES and PES were excluded from this study. The study ended on December 31, 2011. The primary outcome was a composite of all-cause mortality and acute coronary syndrome (ACS). The secondary outcome was the rate of target lesion revascularization (TLR) and stent thrombosis. We analyzed data from 861 consecutive patients who underwent implantation of SES or PES. The median follow-up period was 1671 days (interquartile range 1081 and 2105). Kaplan-Meier curves for the primary endpoint did not significantly differ between the two groups (p = 0.8). The incidence of stent thrombosis was 1.4 and 1.8 per 1,000 person-years in the SES and PES groups, respectively (p = 0.9). The rate of TLR was significantly lower in the SES, than the PES group (12.6 and 38.3 per 1,000 person-years, p = 0.03). The rate of TLR was lower in the group treated with SES than PES, but the primary outcome comprising all-cause mortality and ACS was comparable between the two groups. PMID- 25117763 TI - Structure and mechanism of the unique C2 domain of Aida. AB - Axin interactor, dorsalization-associated (Aida) was identified as a regulatory factor that utilizes its C-terminal region to interact with axis formation inhibitor (Axin). Aida abrogates the Axin-mediated Jun N-terminal kinase activation required for proper dorsalization during zebrafish embryonic development, and thus functions as a proventralization factor. Here, we report the structure of Aida C-terminal fragments, which adopt a conventional C2 domain topology. We also demonstrate that Aida can specifically bind to phosphoinositides in a Ca(2+) -independent manner, and is able to associate with the cell membrane via a novel positively charged surface, namely a basic loop. Mutation of the positively charged patch on the basic loop leads to destabilization of the Aida-membrane association or disruption of the Aida-Axin interaction, resulting in impaired Jun N-terminal kinase inhibition. Together, our findings provide a molecular basis for C2 domain-mediated Aida-membrane and Aida-Axin associations. DATABASE: The atomic coordinates and structure factors of the mouse Aida C2 domain (code: 2QZ5) and the zebrafish Aida C2 domain (code: 2QZQ) have been deposited in the Protein Data Bank (http://www.rcsb.org/) STRUCTURED DIGITAL ABSTRACT: AIDA physically interacts with Axin by anti tag coimmunoprecipitation (View interaction). PMID- 25117764 TI - Predictors of health-related quality of life over time among adolescents and young adults with sickle cell disease. AB - Little is known about what factors affect the health-related quality of life (HRQoL) of adolescents and young adults (AYAs) with sickle cell disease (SCD), and how their HRQoL changes over time. This retrospective study included 87 AYAs attending a SCD Adolescent Clinic who completed a measure of HRQoL at each visit over the course of approximately 1.3 years. Results suggested that the following were associated with poorer physical HRQoL: being female, more healthcare utilization events, and presence of internalizing symptoms. Internalizing and externalizing symptoms were the only factors correlated with poorer psychosocial HRQoL. Generalized linear mixed models indicated that physical and psychosocial HRQoL improved among all participants during the assessment period, and those with externalizing behaviors reported faster improvement in physical HRQoL over time. AYAs with SCD may benefit from early mental health screening and intervention to optimize clinical care. PMID- 25117766 TI - Enhancement mechanisms behind exclusive removal and selective recovery of copper from salt solutions with an aminothiazole-functionalized adsorbent. AB - The aminothiazole-functionalized adsorbent (CEAD) could exclusively remove and to selectively recover copper. The adsorption and separation properties of Cu(II) onto CEAD from aqueous media, with or without salts such as NaNO3, Ca(NO3)2 and Ni(NO3)2, were systematically compared by carrying out single, binary and multiple component static and dynamic experiments. In binary systems, the adsorption capacities of Cu(II) were obviously increased by 39.47%, 47.37% and 57.89% with Ni(NO3)2, NaNO3 and Ca(NO3)2, respectively. Besides, simulation study was performed to selectively recover Cu(II) from multi-component aqueous media, with the separation factor of only 54.91 in aqueous media without salts. The separation factor became infinite in the presence of NaNO3 and the enhancement ratio for Cu(II) was raised by 126.31%. Dynamic adsorption could separate Cu(II) and Ni(II) completely and the amount of effluent for pure Ni(II) increased to 127 BV with the help of NaNO3. In the predominant chelating mode simulated by density functional theory calculation, a metal ion coordinated with three nitrogen atoms and formed a chelating complex with two five-membered rings, and Cu(II) showed stronger coordinating ability than Ni(II) did. Meanwhile, anions exerted significant beneficial effects by electrostatic screening, and thus strengthened the exclusive removal and selective recovery of Cu(II). PMID- 25117765 TI - The different association of epicardial fat with coronary plaque in patients with acute coronary syndrome and patients with stable angina pectoris: analysis using integrated backscatter intravascular ultrasound. AB - OBJECTIVES: We assessed the hypothesis that the epicardial fat is associated with coronary lipid plaque. BACKGROUND: Epicardial fat volume (EFV) is increased in patients with acute coronary syndrome (ACS), and lipid-rich plaques have been associated with acute coronary events. METHODS: We enrolled 112 individuals who underwent percutaneous coronary intervention (PCI) (66 with ACS; 46 with stable angina pectoris [SAP]) and classified plaque components using integrated backscatter intravascular ultrasound as calcified, fibrous, or lipid. Possible effects of PCI on plaque data were minimized by assessing 10-mm vessel lengths proximal to the culprit lesions. Total plaque volume and percentage volumes of individual plaque components were calculated. EFV and abdominal visceral fat area were measured using 64-slice computed tomography. RESULTS: ACS patients had significantly higher EFV than did SAP patients (118 +/- 44 vs.101 +/- 41 mL, p = 0.019). In ACS patients, EFV was correlated with total plaque volume and percentage of lipid plaque (r = 0.27 and 0.31, respectively; p < 0.05). Moreover, an independent interaction between EFV and lipid-rich plaque (odds ratio, 1.04; 95% confidence interval, 1.00-1.07) were revealed. In contrast, in SAP patients, EFV was positively correlated with body mass index and abdominal visceral fat area but not with plaque characteristics. CONCLUSIONS: EFV was associated with lipid-rich plaque in patients with ACS, whereas no correlation between EFV and coronary plaque profile was apparent in SAP patients. Epicardial fat may have a role in the development of lipid plaque, which contributes to the pathogenesis of ACS. PMID- 25117772 TI - Longer examination time improves detection of gastric cancer during diagnostic upper gastrointestinal endoscopy. AB - BACKGROUND & AIMS: It is not clear how the duration of upper endoscopy affects the detection of cancer or premalignant lesions that increase the risk for gastric cancer. We investigated whether the length of time spent performing esophagogastroduodenoscopy (EGD) affects the detection of important pathologic features of the stomach. METHODS: We collected data from 837 symptomatic patients, during a 3-month period in 2010, who underwent a first diagnostic EGD at a tertiary university hospital in Singapore. Endoscopists were classified as fast or slow based on the mean amount of time it took them to perform a normal EGD examination. We used logistic regression to compare between groups the numbers of intestinal metaplasias, gastric atrophies, dysplasias, and cancers detected, using histologic analysis of biopsy samples collected during endoscopy as the standard. RESULTS: Of 224 normal endoscopies, the mean duration was 6.6 minutes (range, 2-32 min). When we used 7 minutes as the cut-off time, 8 endoscopists were considered to have short mean examination times (mean duration, 5.5 +/- 2.1 min; referred to as fast endoscopists), and 8 endoscopists were considered to have long mean examination times (mean duration, 8.6 +/- 4.2 min; referred to as slow endoscopists). Eleven cancers and 81 lesions considered to pose risks for cancer were detected in 86 patients; 1.3% were determined to be cancer, 1.0% were determined to be dysplasia, and 8.7% were determined to be intestinal metaplasia and/or gastric atrophy. Slow endoscopists were twice as likely to detect high-risk lesions as fast endoscopists (odds ratio, 2.50; 95% confidence interval, 1.52-4.12), regardless of whether they were endoscopy staff or trainees. The slow endoscopists also detected 3-fold more neoplastic lesions (cancer or dysplasia; odds ratio, 3.42; 95% confidence interval, 1.25-10.38). CONCLUSIONS: Endoscopists with mean EGD examination times longer than 7 minutes identified a greater number of high-risk gastric lesions than faster endoscopists. Examination time may be a useful indicator of quality assessment for upper endoscopy. Studies are required to test these findings in different populations. PMID- 25117773 TI - Suboptimal surveillance for and knowledge of hepatocellular carcinoma among primary care providers. AB - BACKGROUND & AIMS: A large proportion of patients with cirrhosis are seen only by their primary care provider (PCP). Surveillance for hepatocellular carcinoma (HCC) therefore depends on PCPs in these cases. We aimed to assess PCP knowledge and practice of HCC surveillance. METHODS: We contacted a random sample of 1000 North Carolina PCPs by mail. All PCPs contacted received an introductory letter followed by a 12-item questionnaire addressing HCC surveillance knowledge and practice. RESULTS: A total of 391 PCPs (39%) completed the survey; 89% saw patients with cirrhosis in their practice, but only 45% screened for HCC. Among PCPs who screened for HCC, the most common methods were ultrasound analysis and measurement of alpha-fetoprotein level (66%). Reasons for surveillance included supported by evidence (72%), recommended by medical societies (42%), and malpractice liability for not performing surveillance (26%). Of PCPs who did not screen, 84% referred to gastroenterologists for surveillance decisions, 24% were unaware of recommendations, 8% were uncertain of the benefits, and 8% were concerned about cost. Hepatic resection and liver transplantation were identified as effective therapies by 67% and 56% of PCPs, respectively, but all other effective therapies were identified by less than half (transarterial chemoembolization by 42%, radiofrequency ablation by 35%, and sorafenib by 26%). The ability to identify at least 1 effective therapy was associated independently with surveillance (odds ratio, 2.1; 95% confidence interval, 1.1-4.0). CONCLUSIONS: Most PCPs see patients with cirrhosis, but only a minority screen for HCC. PCP knowledge of effective HCC therapy options is suboptimal. Efforts to enlist PCPs in HCC surveillance may be best served by increasing their knowledge of effective therapies. PMID- 25117774 TI - Trials and tribulations in drug development for nonalcoholic steatohepatitis. PMID- 25117776 TI - Prevalence of chronic narcotic use among children with inflammatory bowel disease. AB - BACKGROUND & AIMS: Narcotic analgesics are not recommended for long-term management of pain for patients with inflammatory bowel disease (IBD), particularly pediatric patients. We compared chronic use of narcotics among children with IBD and the general population and investigated factors associated with narcotic use in the pediatric IBD population. METHODS: This cross-sectional study included children (younger than 18 years old) with continuous enrollment in a large administrative claims database from 2010 through 2011 (n = 4,911,286). Children with IBD were identified through diagnosis codes and dispensation of IBD medication (n = 4344); they were matched for age, sex, and region with 5 children without IBD (n = 21,720). Chronic narcotic use was defined as >=3 dispensements of narcotics. We estimated prevalence odds ratios (PORs) and 95% confidence intervals (CIs), comparing narcotic use on the basis of IBD status and evaluating variables associated with narcotic use by patients with IBD by using conditional and unconditional logistic regression. RESULTS: The prevalence of chronic narcotic use was 5.6% among children with IBD vs 2.3% in the general population (POR, 2.6; 95% CI, 2.2-3.0). Compared with the general population, POR for chronic narcotic use was significantly higher for pediatric IBD patients with psychological impairment (POR, 6.8; 95% CI, 4.3-10.6) than those without (POR, 2.3; 95% CI, 1.9-2.7). Older age, increased healthcare utilization, fracture, and psychological impairment were strongly associated with chronic use of narcotics among children with IBD. CONCLUSIONS: Chronic narcotic use is common in pediatric IBD patients, particularly among those with anxiety and depression. Increased awareness of psychological comorbidity, screening, and treatment may reduce symptoms that lead to narcotic use and its complications. PMID- 25117775 TI - The benefit-to-risk balance of combining infliximab with azathioprine varies with age: a markov model. AB - BACKGROUND & AIMS: Combination therapy with infliximab and azathioprine has demonstrated benefit over monotherapy for moderate-to-severe Crohn's disease. Clinical trials and models have not accounted for age-specific risks associated with these therapies, including the risk of immunosuppression-related cancer and infection. After accounting for these risks, the strategy yielding the greatest benefit may vary with age. METHODS: We assessed age-specific risks and benefits of combination therapy compared with infliximab monotherapy by using Markov modeling. The base case was a 35-year-old male patient with a 1-year time horizon. We assumed the incidence of lymphoma to be 5.28-fold higher with combination therapy. Secondary analyses accounted for life expectancy, therapy beyond 1 year, and age-specific surgical and infection risks. Quality-adjusted life years (QALYs) were calculated for 25- to 75-year old individuals. RESULTS: Combination therapy was found to be of greater benefit in the base case (0.7522 QALYs for combination therapy vs 0.7426 QALYs for monotherapy). Accounting for life years lost, monotherapy was the best approach if the hazard ratio for lymphoma with combination therapy was >8.1 patients who were 75 years old. Monotherapy provided greater net benefit to patients 55, 65, or 75 years old if therapy was extended for 9, 7, or 5 years, respectively. For 25-year-old men, monotherapy resulted in fewer deaths but only yielded greater QALYs if the annual incidence of hepatosplenic T-cell lymphoma exceeded 36/100,000 persons. CONCLUSIONS: After accounting for age-specific risks of lymphoma, infection, and surgical complications, benefits of combination therapy outweighed the risks as a short-term and intermediate-term strategy for most patients with moderate-to severe Crohn's disease who were younger than 65 years. For young male patients, combination therapy yields greater QALYs but at cost of an increased risk of death from lymphoma. PMID- 25117777 TI - A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis. AB - BACKGROUND & AIMS: Infliximab is effective for patients with refractory ulcerative colitis (UC), but few factors have been identified that predict long term outcome of therapy. We aimed to identify a panel of markers associated with outcome of infliximab therapy to help physicians make personalized treatment decisions. METHODS: We collected data from the first 285 patients with refractory UC (41% female; median age, 39 y) treated with infliximab before July 2012 at University Hospitals Leuven, in Belgium. We performed a Cox regression analysis to identify independent factors that predicted relapse-free and colectomy-free survival, and used these factors to create a panel of markers (risk panel). RESULTS: During a median follow-up period of 5 years, 61% of patients relapsed and 20% required colectomy. Independent predictors of relapse-free survival included short-term complete clinical response (odds ratio [OR], 3.75; 95% confidence interval [CI], 2.35-5.97; P < .001), mucosal healing (OR, 1.87; 95% CI, 1.17-2.98; P = .009), and absence of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) (OR, 1.96; 95% CI, 1.23-3.12; P = .005). Independent predictors of colectomy-free survival included short-term clinical response (OR, 7.74; 95% CI, 2.76-21.68; P < .001), mucosal healing (OR, 4.02; 95% CI, 1.16-13.97; P = .028), baseline level of C-reactive protein (CRP) of 5 mg/L or less (OR, 2.95; 95% CI, 1.26-6.89; P = .012), and baseline level of albumin of 35 g/L or greater (OR, 3.03; 95% CI, 1.12-8.22; P = .029). Based on serologic analysis of a subgroup of 112 patients, levels of infliximab greater than 2.5 MUg/mL at week 14 of treatment predicted relapse-free survival (P < .001) and colectomy-free survival (P = .034). A risk panel that included levels of pANCA, CRP, albumin, clinical response, and mucosal healing identified patients at risk for UC relapse or colectomy (both P < .001). CONCLUSIONS: Clinical response and mucosal healing were confirmed as independent predictors of long-term outcome from infliximab therapy in patients with UC. We identified additional factors (levels of pANCA, CRP, and albumin) to create a risk panel that predicts long term outcomes of therapy. Serum levels of infliximab at week 14 of treatment also were associated with patient outcomes. Our risk panel and short-term serum levels of infliximab therefore might be used to guide therapy. PMID- 25117778 TI - Intra-abdominal pressure measurements in term pregnancy and postpartum: an observational study. AB - OBJECTIVE: To determine intra-abdominal pressure (IAP) and to evaluate the reproducibility of IAP-measurements using the Foley Manometer Low Volume (FMLV) in term uncomplicated pregnancies before and after caesarean section (CS), relative to two different reference points and to non-pregnant values. DESIGN: Observational cohort study. SETTING: Secondary level referral center for feto maternal medicine. POPULATION: Term uncomplicated pregnant women as the case group and non-pregnant patients undergoing a laparoscopic assisted vaginal hysterectomy (LAVH) as control group. METHODS: IAP was measured in 23 term pregnant patients, before and after CS and in 27 women immediately after and 1 day after LAVH. The midaxillary line was used as zero-reference (IAPMAL) in all patients and in 13 CS and 13 LAVH patients, the symphysis pubis (IAPSP) was evaluated as additional zero-reference. Intraobserver correlation (ICC) was calculated for each zero-reference. Paired student's t-tests were performed to compare IAP values and Pearson's correlation was used to assess correlations between IAP and gestational variables. MAIN OUTCOME MEASURES: ICC before and after surgery, IAP before and after CS, IAP after CS and LAVH. RESULTS: The ICC for IAPMAL before CS was lower than after (0.71 versus 0.87). Both mean IAPMAL and IAPSP were significantly higher before CS than after: 14.0+/-2.6 mmHg versus 9.8+/-3.0 mmHg (p<0.0001) and 8.2+/-2.5 mmHg versus 3.5+/-1.9 mmHg (p = 0.010), respectively. After CS, IAP was not different from values measured in the LAVH group. CONCLUSION: IAP-measurements using FMLV is reproducible in pregnant women. Before CS, IAP is increased in the range of intra-abdominal hypertension for non pregnant individuals. IAP significantly decreases to normal values after delivery. PMID- 25117781 TI - Klein and Lacan meet 21st century schizoid man: fairy stories for the modern era. AB - Melanie Klein invited us into the phenomenology of the schizoid dilemma through her depictions of the paranoid-schizoid position. By inserting his recursive arrows, Bion extended this conceptualization, showing us the folly of believing that we can ever entirely move beyond the frightening fantasies and realities of social exclusion and isolation. The 21st century has brought, along with the explosion of technology, an expulsion from the social order of many children who have found refuge from isolation and humiliation in the more accessible and less terrifying world of media and technological invention. What may look like narcissism can mask a terrible underlying schizoid failure to enter into the human race. This is the realm of fantasy run amok, where desire becomes alien and alienated such that one is haunted and hunted down by its very possibility. In this universe, conceptualizations from Klein, Bion, and Lacan help us to locate the individual who has become caught in a massive psychic retreat such that there is no subject because there are no objects. To illustrate, I describe my work with a young man who is living in a terrible "zombie zone" where people are not real and therefore are incomprehensible and terribly dangerous. The poignancy of his dilemma is heartbreaking. Perhaps that is one lesson we can still take from our old fairy tales: when one's heart can be broken by another's plight, then comes the possibility of a healing, an entry through that piercing of what had been impenetrable. PMID- 25117782 TI - Why, Mrs. Robinson? The seduction of teenage boys by women in classic films. AB - Utilizing three classic films, and psychoanalytic developmental theory, this paper explores the conscious and unconscious reasons why older women become sexually involved with teenage boys. After a presentation of aspects of young adult and midlife female development and a psychodynamic explanation for the developmental similarities between adolescence and menopause, each of the three films is summarized. The dynamics behind the women's behavior, as presented in the films, are discussed. The third section of the paper discusses similarities and differences among the three women and the negative effects on the boys' development. PMID- 25117779 TI - Molecular basis and genetic predisposition to intracranial aneurysm. AB - Intracranial aneurysms, also called cerebral aneurysms, are dilatations in the arteries that supply blood to the brain. Rupture of an intracranial aneurysm leads to a subarachnoid hemorrhage, which is fatal in about 50% of the cases. Intracranial aneurysms can be repaired surgically or endovascularly, or by combining these two treatment modalities. They are relatively common with an estimated prevalence of unruptured aneurysms of 2%-6% in the adult population, and are considered a complex disease with both genetic and environmental risk factors. Known risk factors include smoking, hypertension, increasing age, and positive family history for intracranial aneurysms. Identifying the molecular mechanisms underlying the pathogenesis of intracranial aneurysms is complex. Genome-wide approaches such as DNA linkage and genetic association studies, as well as microarray-based mRNA expression studies, provide unbiased approaches to identify genetic risk factors and dissecting the molecular pathobiology of intracranial aneurysms. The ultimate goal of these studies is to use the information in clinical practice to predict an individual's risk for developing an aneurysm or monitor its growth or rupture risk. Another important goal is to design new therapies based on the information on mechanisms of disease processes to prevent the development or halt the progression of intracranial aneurysms. PMID- 25117783 TI - Emotions and cognitions: a critique of the dichotomous view of mental function. AB - Many approaches to the psyche, models of therapy, and neuroscience tend to view emotional and cognitive brain functions as separate entities. Such a focus on one of these two aspects of mental function, at times comes at the expense of ignoring the other. In this paper emotions and cognitions, along with perceptions and other elements of the internal and external contexts, are viewed as relevant vectors in a matrix of information. Through the processes of pattern completion and noise reduction, information in each of these vectors may evoke memories in the same or other vectors that are used in the formation of a subjective understanding of each experience. The important roles of the external (physical, temporal, relevant events, etc.) and internal (emotional, affective, hormonal, medications, etc.) contexts in the formation of such subjective experiences will be discussed. The use of this view in broader and more comprehensive psychotherapeutic approaches and combined pharmacological and psychological treatment is explored. PMID- 25117784 TI - The centrality of guilt: working with ultra-orthodox Jewish patients in Israel. AB - The ultra-orthodox Jewish (Haredi) community in Israel is characterized by strict observance of the requirements of orthodox Jewish life. Psychoanalytic psychotherapy within this community brings us into contact with guilt as a central emotion throughout the therapeutic process. The exposure to new concepts, ways of thought and a previously unknown space, together with increased awareness of internal wishes and drives, are experienced as forbidden areas that arouse an awakening of conscience and a sense of guilt. The author's cases illustrate these conflicts. PMID- 25117780 TI - Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study. AB - BACKGROUND AND PURPOSE: Studies investigating the association between 25 hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, beta = 0.023, P = 0.01; highest, beta = 0.021, P = 0.02), Digit Vigilance Task (lowest, beta = 0.009, P = 0.05; highest, beta = 0.01, P = 0.02) and Power of Attention (lowest, beta = 0.017, P = 0.02; highest, beta = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, beta = 0.021, P = 0.02; highest, beta = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment. PMID- 25117785 TI - Agency, surrender (and grace) in the psychoanalytic process. PMID- 25117786 TI - Psychoanalysis: the sacred and the profane. PMID- 25117792 TI - A comparison of the effects of desflurane versus propofol on transcranial motor evoked potentials in pediatric patients. AB - PURPOSE: The aim was to compare the effects of propofol and desflurane anesthesia on transcranial motor evoked potentials (MEPs) from pediatric patients undergoing surgery for spinal deformities. METHODS: Desflurane and propofol cohorts (25 patients each) were obtained retrospectively and matched for patient characteristics and surgical approach. MEPs from the thenar eminence and abductor hallucis were compared during maintenance anesthesia on desflurane (0.6-0.8 MAC) or propofol infusion (150-300 MUg/kg/min). MEP amplitudes and durations were obtained for successive 30-min intervals for 150 min, beginning 60 min after maintenance anesthesia. RESULTS: Mean peak to peak amplitudes of MEPs under desflurane anesthesia from the thenar eminence (419 MUV) and abductor hallucis (386 MUv) were not significantly different from those under propofol (608 MUV, 343 MUV, thenar, and abductor hallucis, respectively). Stimulation was greater by 42 V and 136 mA, and trains were slightly longer in the desflurane compared to the propofol group (p < 0.05). Most MEP amplitudes for the desflurane and propofol cohorts remained the same or increased (71 % of cases) when those after 150 min were compared to those in the first 30-min interval. CONCLUSIONS: MEPs with good amplitudes were obtained under desflurane only anesthesia that were comparable to propofol only anesthesia in pediatric patients during surgery for spinal deformities. There was no evidence for anesthetic fade over the time period examined. When used by itself, desflurane can be considered a viable alternative to propofol anesthesia. PMID- 25117793 TI - Staff-resident interactions in long-term care for people with dementia: the role of meeting psychological needs in achieving residents' well-being. AB - OBJECTIVES: The aim of this study is to explore the extent to which staff resident interactions address or undermine residents' psychological needs and how such interactions are associated with residents' well-being. METHOD: Data on staff-resident interactions and residents' well-being were collected for 51 residents from nine long-term care settings using dementia care mapping (DCM). DCM yields a count and detailed description of staff-resident interactions that either address (personal enhancers - PEs) or undermine (personal detractions - PDs) residents' psychological needs, and every 5-minute scores for each resident's mood and engagement (ME-value). The relationship between PEs and PDs and well-being was analysed by studying residents' ME-values before and three time frames after a PE or PD occurred. RESULTS: A total of 76 PEs and 33 PDs were observed. The most common PEs were those addressing psychological needs for comfort and occupation. However residents' well-being increased most often after PEs that addressed residents' need for identity, attachment and inclusion. The most common PDs were those which undermined the need for comfort, inclusion and occupation. Residents' well-being decreased most often after PDs that undermined the need for comfort. CONCLUSION: Increasing interactions which address residents' need for attachment, identity and inclusion and eliminating interactions which undermine residents' need for comfort may be particularly important in achieving residents' well-being. In the long run, residents' well being could be achieved by staff availing of the opportunities to empower and facilitate residents, thus meeting their needs for occupation. These findings provide directions for training in person-centred care. PMID- 25117794 TI - Influence of KIR genes and their HLA ligands in the pathogenesis of leprosy in a hyperendemic population of Rondonopolis, Southern Brazil. AB - BACKGROUND: The objective of this study was to investigate the association between KIR genes and the immunopathogenesis of leprosy. METHODS: The types of KIR and HLA genes were evaluated by PCR-SSOP-Luminex in 408 patients with leprosy and 413 healthy individuals. Statistical analysis was performed using the Chi square or Fisher's exact test and stepwise multivariate analysis. RESULTS: There was a higher frequency of activating KIR genes (KIR2DS1, 2DS2 and 3DS1) together with their HLA ligands in the tuberculoid (TT) group as compared to the lepromatous leprosy (LL) group. KIR2DL2/2DL2-C1 was more frequent in the patient, TT and LL groups than in the control group. Borderline patients presented a higher frequency of inhibitory pairs when compared to the control group, and a higher frequency of activating pairs as compared to the LL group. Multivariate analysis confirmed the associations and demonstrated that being a female is a protective factor against the development of the disease per se and the more severe clinical form. CONCLUSIONS: This study showed that activating and inhibitory KIR genes may influence the development of leprosy - in particular, activating genes may protect against the more aggressive form of the disease - thereby demonstrating the role of NK cells in the immunopathology of the disease. PMID- 25117795 TI - A short peptide from frog skin accelerates diabetic wound healing. AB - Delayed wound healing will result in the development of chronic wounds in some diseases, such as diabetes. Amphibian skins possess excellent wound-healing ability and represent a resource for prospective wound-healing promoting compounds. A potential wound-healing promoting peptide (CW49; amino acid sequence APFRMGICTTN) was identified from the frog skin of Odorrana grahami. It promotes wound healing in a murine model with a full-thickness dermal wound in both normal and diabetic animals. In addition to its strong angiogenic ability with respect to the upregulation of some angiogenic proteins, CW49 also showed a significant anti-inflammatory effect in diabetic wounds, which was very important for healing chronic wounds. CW49 had little effect on re-epithelialization, resulting in no significant effect on wound closure rate compared to a vehicle control. Altogether, this indicated that CW49 might accelerate diabetic wound healing by promoting angiogenesis and preventing any excessive inflammatory response. Considering its favorable traits as a small peptide that significantly promotes angiogenesis, CW49 might be an excellent candidate or template for the development of a drug for use in the treatment of diabetic wounds. PMID- 25117797 TI - The selective adsorption of tellurium in the aluminosilicate regions of AFI- and MOR-type microporous crystals. AB - Attempts have been made to load tellurium (Te) atoms into the one-dimensional nano-channels of microporous crystals of aluminophosphate AlPO4-5 and of aluminosilicate mordenites of the Na(+) form (Na-MOR) and the H(+)-form (H-MOR) at 673 K. The density of the atoms adsorbed was in the sequence 0 ~ AlPO4-5 ? H MOR < Na-MOR. AlPO4-5 provides a shallow potential of periodical charge fluctuation for Te atoms, from the alternate ordering of Al and P atoms through O atoms. Mordenite offers a sufficiently strong potential for Te adsorption, but the magnitude varies with the type of cation. Dipoles between framework AlO2(-) anion sites and their Na(+) counter-ions in Na-MOR provide a stronger potential than the Bronsted acid points in H-MOR. The adsorption of Te atoms in the silico aluminophosphate SAPO-5 was between that of AlPO4-5 and H-MOR, leading us to suspect that Te atoms are selectively adsorbed in the aluminosilicate regions accompanying the Bronsted acid points distributed in the major aluminophosphate network. The aluminosilicate regions in SAPO-5 are below 500 nm in size and are distributed throughout a single crystal. PMID- 25117796 TI - Pharmacological characterisation of the mechanisms underlying the relaxant effect of adrenomedullin in the rat carotid artery. AB - OBJECTIVES: We investigated the mechanisms underlying the relaxant effect of adrenomedullin (AM) in the rat carotid artery and verified the expression of AM system components in this tissue. METHODS: The carotid artery was isolated from male Wistar rats and immunohistochemical, Western immunoblotting, real-time polymerase chain reaction and functional assays were conducted. KEY FINDINGS: Protein and mRNA expression of AM, calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP)1, 2, 3 were detected in carotid segments from male Wistar rats. Immunohistochemical assays showed that AM and CRLR receptors are expressed in the endothelium and smooth muscle cells. Functional assays showed that AM concentration dependently relaxed carotid rings with intact endothelium. Endothelial removal reduced, but not abolished, the relaxation induced by AM. AM22-52 (selective antagonist for AM receptors) and calcitonin gene-related peptide (CGRP)8-37 (selective CGRP receptor antagonist) reduced AM-induced relaxation in endothelium-intact rings. Pre-incubation of endothelium-intact rings with N-nitro-L-arginine methyl ester, 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or Rp-8-Bromo-?-phenyl-1,N2 ethenoguanosine 3',5'cyclic monophosphorothioate reduced AM-induced relaxation. Inhibition of cyclooxygenase-1 and protein kinase A (PKA) reduced AM-induced relaxation. The relaxation induced by AM was attenuated by the K(+) channel blockers apamin and glibenclamide. AM increased nitrate levels and 6-keto prostaglandin F1alpha (stable product of prostacyclin) in the rat carotid. In endothelium-denuded rings, AM22-52 , glibenclamide and PKA inhibition by H89 reduced AM-induced relaxation. CONCLUSIONS: The novelty of this work is that it first demonstrated functionally that AM-induced relaxation is mediated by AM and CGRP receptors located on the endothelium and AM receptors located on smooth muscle of rat carotid arteries. AM-induced relaxation involves the nitric oxide cGMP pathway, a vasodilator prostanoid, the opening of K(+) channels and the activation of PKA. PMID- 25117799 TI - Recent developments in the search for a cure for HIV-1 infection: targeting the latent reservoir for HIV-1. AB - HIV-1 infection can now be readily controlled with combination antiretroviral therapy. However, the virus persists indefinitely in a stable latent reservoir in resting CD4(+) T cells. This reservoir generally prevents cure of the infection with combination antiretroviral therapy alone. However, several recent cases of potential HIV-1 cure have generated renewed optimism. Here we review these cases and consider new developments in our understanding of the latent reservoir. In addition, we consider clinical aspects of curative strategies to provide a more realistic picture of what a generally applicable cure for HIV-1 infection is likely to entail. PMID- 25117800 TI - Cure of HIV infection: is the long wait over? PMID- 25117798 TI - Progress in HIV-1 vaccine development. AB - The past 2 years have seen a number of basic and translational science advances in the quest for development of an effective HIV-1 vaccine. These advances include discovery of new envelope targets of potentially protective antibodies, demonstration that CD8(+) T cells can control HIV-1 infection, development of immunogens to overcome HIV-1 T-cell epitope diversity, identification of correlates of transmission risk in an HIV-1 efficacy trial, and mapping of the coevolution of HIV-1 founder envelope mutants in infected subjects with broad neutralizing antibodies, thereby defining broad neutralizing antibody developmental pathways. Despite these advances, a promising HIV-1 vaccine efficacy trial published in 2013 did not prevent infection, and the HIV-1 vaccine field is still years away from deployment of an effective vaccine. This review summarizes what some of the scientific advances have been, what roadblocks still remain, and what the most promising approaches are for progress in design of successful HIV-1 vaccine candidates. PMID- 25117802 TI - Prenatal adverse life events increase the risk for atopic diseases in children, which is enhanced in the absence of a maternal atopic predisposition. AB - BACKGROUND: There is evidence to suggest an association between prenatal maternal stress and the development of asthma or other atopic diseases in offspring. Yet, insights on the lasting effect of multiple, common prenatal stressors are rare, and the effects of prenatal timing are poorly understood. Further, it remains elusive if prenatal life events modify the risk for atopic diseases in the context of a parental predisposition to atopy. OBJECTIVE: We tested whether women's experiences of common, adverse life events during the first or second half of pregnancy predicted the risk of developing atopic diseases in their children and whether a reported parental atopic disease moderated this association. METHODS: We calculated the odds of a child developing asthma, eczema, and/or allergic rhinitis at ages 6 or 14 years, depending on maternal prenatal exposure to negative life events in a sample of 1587 children from the Western Australian Pregnancy Cohort (Raine) Study by using multivariable logistic regression. RESULTS: We observed that the likelihood of asthma and eczema at age 14 years was significantly increased in children of mothers who had experienced adverse life events during the second half of gestation (1 life event: adjusted odds ratio for asthma, 2.08 [95% CI, 1.22-3.54]). A stronger increase in the odds to develop asthma upon prenatal life events was present in children of mothers without asthma compared with mothers with asthma. CONCLUSIONS: Maternal adverse life events during the second half of gestation are linked to an increased risk for the development of atopic disorders, asthma, and eczema, in the case of asthma, particularly in the absence of a maternal asthma. PMID- 25117803 TI - Successful RAG1-SCID gene therapy depends on the level of RAG1 expression. PMID- 25117804 TI - Reply: To PMID 24332219. PMID- 25117805 TI - Study design and protocol for a theory-based behavioral intervention focusing on maintenance of weight loss: the Maintenance After Initiation of Nutrition TrAINing (MAINTAIN) study. AB - BACKGROUND: Obesity is a significant public health problem. Although various lifestyle approaches are effective for inducing significant weight loss, few effective behavioral weight maintenance strategies have been identified. It has been proposed that behavior maintenance is a distinct state that involves different psychological processes and behavioral skills than initial behavior change. Previously, we created a conceptual model that distinguishes behavior initiation from maintenance. This model was used to generate Maintenance After Initiation of Nutrition TrAINing (MAINTAIN), an intervention to enhance weight loss maintenance following initiation. The effectiveness of MAINTAIN is being evaluated in an ongoing trial, the rationale and procedures of which are reported herein. METHODS/DESIGN: Veterans aged <= 75 with body mass index >= 30 kg/m(2) participate in a 16-week, group-based weight loss program. Participants who lose >= 4 kg by the end of 16 weeks (target n = 230) are randomized 1:1 to receive (a) usual care for 56 weeks or (b) MAINTAIN, a theoretically-informed weight loss maintenance intervention for 40 weeks, followed by 16 weeks of no intervention contact. MAINTAIN involves 3 in-person group visits that transition to 8 individualized telephone calls with decreasing contact frequency. MAINTAIN focuses on satisfaction with outcomes, weight self-monitoring, relapse prevention, and social support. We hypothesize that, compared to usual care, MAINTAIN will result in at least 3.5 kg less regain and better relative levels of caloric intake and physical activity over 56 weeks, and that it will be cost effective. DISCUSSION: If effective, MAINTAIN could serve as a model for redesigning existing weight loss programs. CLINICALTRIALSGOV IDENTIFIER: NCT01357551. PMID- 25117806 TI - A protocol to evaluate the efficacy, perceptions, and cost of a cholesterol packaging approach to improve medication adherence. AB - PURPOSE: Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for cardiovascular disease (CVD), a leading cause of death in the United States. Despite clinical practice guidelines aimed at facilitating LDL-C control, many Veterans do not achieve guideline-recommended LDL-C levels. METHODS: We describe a study focused on VA healthcare system users at risk for CVD (i.e., LDL-C level >130 mg/dl and/or <80% cholesterol pill refill adherence in the last 12 months). We are conducting a two and a half year randomized controlled trial (i.e., intervention administered over 12 months) among Veterans with uncontrolled cholesterol receiving care at select VA-affiliated primary care clinics in North Carolina. We anticipate enrolling 250 diverse patients (10% women; 40% African American). Patients are randomized to an educational control group or intervention group. Intervention group participants' medication is provided in special blister packaging labeled for daily use that includes reminders; MeadWestvaco Corporation's pre-filled DosePak(r) contains standard doses of statins in accordance with the existing prescriptions. CONCLUSIONS: Pre filled blister packaging may provide an inexpensive solution to improve medication adherence. Our study enrolls a diverse sample and provides information about whether an adherence packaging intervention can: 1) improve medication adherence; 2) improve patients' LDL-C levels; 3) be well received by patients and providers; and 4) provide a cost effective solution to improve medication adherence. PMID- 25117807 TI - Lack of association between leptin levels and leptin gene polymorphism in obese women. AB - The aim of the present study was to evaluate the relationship between oligopolymorphism in the 25th codon of leptin gene and obesity. Eighty-seven obese women and 75 healthy women were constituted obese and control groups. Body fat percent, fat mass and lean body mass were determined by bioimpedance meter and leptin levels were determined. The presence of 25th codon oligopolymorphism in the leptin gene was done by PCR-RFLP technique. Mean leptin levels were 38.5+/ 22.0 ng/ml, and 147.9+/-44.8 ng/ml in the control and obese groups, respectively. The correlations of serum leptin level to body fat percentage and fat mass in the control group were significant. The correlations in the obese group were not significant. This data implies that the difference of leptin levels between control and obese groups are more likely to be associated with alterations in the leptin gene other than 25th codon or alterations in the leptin receptor gene. PMID- 25117808 TI - Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma. AB - BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly elevated (?181.5 U l(-1)). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit. CONCLUSIONS: Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design. PMID- 25117809 TI - Guidelines for the use of cell lines in biomedical research. AB - Cell-line misidentification and contamination with microorganisms, such as mycoplasma, together with instability, both genetic and phenotypic, are among the problems that continue to affect cell culture. Many of these problems are avoidable with the necessary foresight, and these Guidelines have been prepared to provide those new to the field and others engaged in teaching and instruction with the information necessary to increase their awareness of the problems and to enable them to deal with them effectively. The Guidelines cover areas such as development, acquisition, authentication, cryopreservation, transfer of cell lines between laboratories, microbial contamination, characterisation, instability and misidentification. Advice is also given on complying with current legal and ethical requirements when deriving cell lines from human and animal tissues, the selection and maintenance of equipment and how to deal with problems that may arise. PMID- 25117810 TI - Senescent cancer-associated fibroblasts secrete active MMP-2 that promotes keratinocyte dis-cohesion and invasion. AB - BACKGROUND: Previous studies have demonstrated that senescent cancer-associated fibroblasts (CAFs) derived from genetically unstable oral squamous cell carcinomas (GU-OSCC), unlike non-senescent CAFs from genetically stable carcinomas (GS-OSCC), promoted keratinocyte invasion in vitro in a paracrine manner. The mechanism by which this occurs is unclear. METHODS: Previous work to characterise the senescent-associated secretory phenotype (SASP) has used antibody arrays, technology that is limited by the availability of suitable antibodies. To extend this work in an unbiased manner, we used 2D gel electrophoresis and mass spectroscopy for protein identification. Matrix metalloproteinases (MMPs) were investigated by gelatin zymography and western blotting. Neutralising antibodies were used to block key molecules in the functional assays of keratinocyte adhesion and invasion. RESULTS: Among a variety of proteins that were differentially expressed between CAFs from GU-OSCC and GS OSCC, MMP-2 was a major constituent of senescent CAF-CM derived from GU-OSCC. The presence of active MMP-2 was confirmed by gelatine zymography. MMP-2 derived from senescent CAF-CM induced keratinocyte dis-cohesion and epithelial invasion into collagen gels in a TGF-beta-dependent manner. CONCLUSIONS: Senescent CAFs from GU OSCC promote a more aggressive oral cancer phenotype by production of active MMP 2, disruption of epithelial adhesion and induction of keratinocyte invasion. PMID- 25117811 TI - MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer. AB - BACKGROUND: Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance. METHODS: We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining. RESULTS: The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour initiating potential and induced drug resistance. A high expression level of miR 1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. CONCLUSIONS: miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients. PMID- 25117812 TI - Plasma microRNA profiles: identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma. AB - BACKGROUND: Recent studies have demonstrated that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory particles. This study was designed to detect novel microRNAs in plasma for cancer detection and monitoring using microRNA array-based approaches in oesophageal squamous cell carcinoma (ESCC) patients. METHODS: Through the integration of two Toray 3D-Gene microRNA array-based approaches to compare plasma microRNA levels between ESCC patients and healthy volunteers and between preoperative and postoperative ESCC patients, we identified a novel plasma biomarker in ESCC. RESULTS: (1) Eight upregulated and common microRNAs (miR-15b, 16, 17, 25, 19b, 20a, 20b, and 106a) were selected using two high-resolution microRNA array approaches. (2) Test-scale analyses by quantitative RT-PCR validated a significant higher levels of plasma miR-19b (P=0.0020) and miR-25 (P=0.0030) in ESCC patients than controls. However, a significant correlation was observed between plasma miR-19b levels and concentrations of red blood cells (P=0.0073) and haemoglobin (P=0.0072). (3) miR-25 expression was found to be significantly higher in ESCC tissues (P=0.0157) and ESCC cell lines (P=0.0093) than in normal tissues and fibroblasts. (4) In a large-scale validation analysis, plasma miR-25 levels were significantly higher in 105 preoperative (P<0.0001) ESCC patients who underwent curative oesophagectomy and 20 superficial ESCC patients who underwent endoscopic resection (P<0.0001) than in 50 healthy volunteers. (5) Plasma miR-25 levels were significantly reduced in postoperative samples than in preoperative samples (P<0.0005) and were significantly increased during ESCC recurrences (P=0.0145). CONCLUSIONS: Plasma miR-25 might be a clinically useful biomarker for cancer detection and the monitoring of tumour dynamics in ESCC patients. PMID- 25117813 TI - The lag time in initiating clinical testing of new drugs in combination with radiation therapy, a significant barrier to progress? AB - BACKGROUND: The clinical development of new drugs with radiation appears to be limited. We hypothesised that phase I clinical trials with radiation therapy (RT) are initiated too late into a new drug's lifetime, impeding the ability to complete RT-drug development programmes before patent expiration. METHODS: We identified novel drug-radiation phase I combination trials performed between 1980 and 2012 within the PubMed and ClinicalTrials.gov databases. Data gathered for each drug included: date the initial phase I trial with/without RT was opened/published, date of the published positive phase III trials, and patent expiration dates. Lag time was defined as the interval between opening of the phase I trial without RT and the opening of the phase I with RT. Linear regression was used to model how the lag time has changed over time. RESULTS: The median lag time was 6 years. The initial phase I trial with RT was typically published 2 years after the first published positive phase III trial and 11 years before patent expiration. Using a best-fit linear model, lag time decreased from 10 years for phase I trials published in 1990 to 5 years in 2005 (slope significantly non-zero, P<0.001). CONCLUSIONS: Clinical drug development with RT commences late in the life cycle of anti-cancer agents. Taking into account the additional time required for late-phase clinical trials, the delay in initiating clinical testing of drug-RT combinations discourages drug companies from further pursuing RT-based development. Encouragingly, lag time appears to be decreasing. Further reduction in lag time may accelerate RT-based drug development, potentially improving patient outcomes. PMID- 25117814 TI - Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway. AB - BACKGROUND: A major therapeutic challenge for breast cancer is the ability of cancer cells to evade killing of conventional chemotherapeutic agents. We have recently reported the actin-bundling protein (fascin) as a major regulator of breast cancer metastasis and survival. METHODS: Survival of breast cancer patients that received chemotherapy and xenograft tumour model was used to assess the effect of chemotherapy on fascin-positive and -negative breast cancer cells. Molecular and cellular assays were used to gain in-depth understanding of the relationship between fascin and chemoresistance. RESULTS: We showed a significant correlation between fascin expression and shorter survival in breast cancer patients who received chemotherapy. In xenograft experiments, fascin-positive cancer cells displayed significantly more resistance to chemotherapy-mediated apoptotic cell death than fascin-negative counterparts. This increased chemoresistance was at least partially mediated through PI3K/Akt signalling, and was paralleled by increased FAK phosphorylation, enhanced expression of the inhibitor of apoptosis proteins (XIAP and Livin) and suppression of the proapoptotic markers (caspase 9, caspase 3 and PARP). CONCLUSIONS: This is the first report to demonstrate fascin involvement in breast cancer chemotherapeutic resistance, supporting the development of fascin-targeting drugs for better treatment of chemoresistance breast cancer. PMID- 25117815 TI - Identification of 33 candidate oncogenes by screening for base-specific mutations. AB - BACKGROUND: Genes with recurrent codon-specific somatic mutations are likely drivers of tumorigenesis and potential therapeutic targets. Hypermutable cancers may represent a sensitive system for generation and selection of oncogenic mutations. METHODS: We utilised exome-sequencing data on 25 sporadic microsatellite-instable (MSI) colorectal cancers (CRCs) and searched for base specific somatic mutation hotspots. RESULTS: We identified novel mutation hotspots in 33 genes. Fourteen genes displayed mutations in the validation set of 254 MSI CRCs: ANTXR1, MORC2, CEP135, CRYBB1, GALNT9, KRT82, PI15, SLC36A1, CNTF, GLDC, MBTPS1, OR9Q2, R3HDM1 and TTPAL. A database search found examples of the hotspot mutations in multiple cancer types. CONCLUSIONS: This work reveals a variety of new recurrent candidate oncogene mutations to be further scrutinised as potential therapeutic targets. PMID- 25117817 TI - EGFR expression is associated with decreased benefit from trastuzumab in the NCCTG N9831 (Alliance) trial. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) has been hypothesised to modulate the effectiveness of anti-HER2 therapy. We used a standardised, quantitative immunofluorescence assay and a novel EGFR antibody to evaluate the correlation between EGFR expression and clinical outcome in the North Central Cancer Treatment Group (NCCTG) N9831 trial. METHODS: Tissue microarrays were constructed that allowed analysis of 1365 patients randomly assigned to receive chemotherapy alone (Arm A), sequential trastuzumab after chemotherapy (Arm B) and chemotherapy with concurrent trastuzumab (Arm C). Measurement of EGFR was performed using the EGFR antibody, D38B1, on the fluorescence-based AQUA platform. The result was validated using an independent retrospective metastatic breast cancer cohort (n=130). RESULTS: Epidermal growth factor receptor assessed as a continuous (logarithmic transformed) variable shows an association with disease-free survival in Arm C (P=0.009) but not in Arm A or B. High EGFR expression was associated with worse outcome (Hazard ratio (HR)=2.15; 95% CI 1.28 3.60, P=0.004). Validation in a Greek metastatic breast cancer cohort showed an HR associated with high EGFR expression of 1.92 (P=0.0073). CONCLUSIONS: High expression of EGFR appears to be associated with decreased benefit from adjuvant concurrent trastuzumab. Since other treatment options exist for HER2-driven tumours, further validation of these data may select patients for alternative or additive therapy. PMID- 25117816 TI - Coexistence of KRAS mutation with mutant but not wild-type EGFR predicts response to tyrosine-kinase inhibitors in human lung cancer. PMID- 25117818 TI - Risk of leukaemia or cancer in the central nervous system among children living in an area with high indoor radon concentrations: results from a cohort study in Norway. AB - BACKGROUND: Over the past few years, there has been growing interest in assessing the relationship between exposure to radon at home and the risk of childhood cancer. Previous studies have produced conflicting results, probably because of limitations assessing radon exposure, too few cancer cases and poorly documented health statistics. METHODS: We used a cohort approach of 0-15-year-old children to examine whether residential radon exposure was associated with childhood leukaemia and cancer in the central nervous system in the Oslo region. The study was based on Norwegian population registers and identified cancer cases from The Cancer Registry of Norway. The residence of every child was geo-coded and assigned a radon exposure. RESULTS: In all, 712 674 children were followed from 1967 to 2009 from birth to date of cancer diagnosis, death, emigration or 15 years of age. A total of 864 cancer cases were identified, 437 children got leukaemia and 427 got cancer in the central nervous system.Conclusions or interpretation:No association was found for childhood leukaemia. An elevated nonsignificant risk for cancer in the central nervous system was observed. This association should be interpreted with caution owing to the crude exposure assessment and possibilities of confounding. PMID- 25117819 TI - BRAF(V600E) melanoma cells secrete factors that activate stromal fibroblasts and enhance tumourigenicity. AB - BACKGROUND: Melanoma, the most lethal form of skin cancer, is responsible for over 80% of all skin cancer deaths and is highly metastatic, readily spreading to the lymph nodes or metastasising to other organs. The frequent genetic mutation found in metastatic melanoma, BRAF(V600E), results in constitutive activation of the mitogen-activated protein kinase pathway. METHODS: In this study, we utilised genetically engineered melanoma cell lines and xenograft mouse models to investigate how BRAF(V600E) affected cytokine (IL-1beta, IL-6, and IL-8) and matrix metalloproteinase-1 (MMP-1) expression in tumour cells and in human dermal fibroblasts. RESULTS: We found that BRAF(V600E) melanoma cells expressed higher levels of these cytokines and of MMP-1 than wild-type counterparts. Further, conditioned medium from the BRAF(V600E) melanoma cells promoted the activation of stromal fibroblasts, inducing expression of SDF-1 and its receptor CXCR4. This increase was mitigated when the conditioned medium was taken from melanoma cells treated with the BRAF(V600E) specific inhibitor, vemurafenib. CONCLUSIONS: Our findings highlight the role of BRAF(V600E) in activating the stroma and suggest a mechanistic link between BRAF(V600E) and MMP-1 in mediating melanoma progression and in activating adjacent fibroblasts in the tumour microenvironment. PMID- 25117821 TI - Hyperfibrinogenemia in appendicitis: a new predictor of perforation in children. AB - PURPOSE: Acute appendicitis is the most common emergency abdominal inflammation requiring operation in children. As an acute-phase protein, plasma fibrinogen always increases with inflammation or tissue necrosis. This had brought about the assumption that hyperfibrinogenemia in patients with appendicitis may have a predictive ability for the preoperative diagnosis of appendiceal. Aim of this retrospective study was to assess the diagnostic value of hyperfibrinogenemia as a preoperative laboratory marker for appendiceal perforation in children with acute appendicitis. METHODS: We screened 466 children (168 girls, 298 boys, mean age, 7.6 years) with histologically confirmed acute appendicitis who received laparoscopic or open appendectomy between January 2012 and April 2014 in a pediatric surgery department of an academic teaching hospital. A retrospective review of the medical records including appendiceal perforation rate and laboratory results was conducted. RESULTS: Mean plasma fibrinogen level of all patients was 4.89 g/L (SD 1.74 g/L, range 1.94-15 g/L, median 4.61 mg/dL). Children with appendiceal perforation had a mean fibrinogen level of 6.18 g/L (SD 1.83 g/L, range 3.02-15 g/L, median 5.79 g/L), which was significantly higher than those with non-perforated children (P = 0.0001). The specificity of hyperfibrinogenemia for appendiceal perforation was 0.82 in comparison with 0.25 for white blood count (WBC) and 0.34 for C-reactive protein (CRP). Sensitivity was 0.74 compared with 0.76 for WBC and 0.94 for CRP. CONCLUSION: Children with hyperfibrinogenemia and clinical symptoms of appendicitis may be regarded as a higher risk of appendiceal perforation than whose fibrinogen level is normal. PMID- 25117822 TI - Astrocytic growth through the autocrine/paracrine production of IL-1beta in the early infectious phase of fowl glioma-inducing virus. AB - Fowl glioma is characterized morphologically by multiple nodular astrocytic growth with disseminated non-suppurative encephalitis. The disease is caused by fowl glioma-inducing virus (FGV) and its variants, belonging to subgroup A of avian leukosis virus (ALV-A). Fifty-seven FGV variants have so far been isolated from Japanese fowls and these variants have a variable degree of glioma inducibility. However, how these ALVs induce glioma with different degrees and frequencies has not been fully elucidated. In this study, we investigated the relationship between intracerebral viral replication and astrocytic growth in the early infectious phase. Replication abilities of two ALV strains, Sp-53 (a FGV variant) and ALV-based replication-competent vector RCAS(A) without glioma inducibility, were compared in the brains of C/O specific pathogen free chickens at 35 days of age. Sp-53 replicated faster than RCAS(A), and the histological score and the level of interleukin (IL)-1beta in brains increased depending on the level of intracerebral viral RNA. Up-regulation of IL-1beta was also demonstrated in primary cultured astrocytes. These results suggest that the astrocytic growth in this phase is enhanced through the autocrine/paracrine production of IL-1beta in the FGV-infected astrocytes. PMID- 25117823 TI - Association between sleep quality and cardiovascular damage in pre-dialysis patients with chronic kidney disease. AB - BACKGROUND: Poor sleep quality, a novel risk factor of cardiovascular diseases (CVD), is highly prevalent in patients with chronic kidney disease (CKD). The association between poor sleep quality and cardiovascular damage in patients with CKD is unclear. This study is aimed to assess the prevalence and related risk factors of sleep disturbance and determine the relationship between sleep quality and cardiovascular damage in Chinese patients with pre-dialysis CKD. METHODS: A total of 427 pre-dialysis CKD patients (mean age = 39 +/- 15 years, 260 male/167 female) were recruited in this study. The demographics and clinical correlates were collected. The sleep quality was measured by the Pittsburgh Sleep Quality Index (PSQI), whereas the cardiovascular damage indicators (the Early/late diastolic peak flow velocity (E/A) ratio and left ventricular mass index (LVMI)) were determined by an echocardiographic examination. RESULTS: Of the CKD patients, 77.8% were poor sleepers as defined by a PSQI score > 5. Median estimated glomerular filtration rate (eGFR) was 69.4(15.8-110.9) ml/min/1.73 m(2). Logistic regression analysis revealed that left ventricular hypertrophy (LVH) was independently associated with the PSQI score (OR = 1.092, 95% CI = 1.011-1.179, p = 0.025), after adjustment for age, sex and clinical systolic blood pressure, diastolic blood pressure, Phosphate, Intact parathyroid hormone (iPTH), Hemoglobin and eGFR. The linear regression analysis showed that the E/A ratios were independently associated with the PSQI score (beta = -0.115, P = 0.028) after adjustment for a series of potential confounding factors. CONCLUSIONS: Poor sleep quality, which is commonly found in pre-dialysis CKD patients, is an independent factor associated with cardiovascular damage in CKD patients. Our finding implies that the association between poor sleep and CVD might be mediated by cardiac remodeling. PMID- 25117824 TI - At the second glance: stability of neural responses toward visual sexual stimuli. AB - INTRODUCTION: Studies investigating the neural responses toward sexual stimuli can provide an important basis for further understanding disorders of sexual functioning. Although our knowledge of the neural correlates of sexual stimulus processing has increased considerably in the last decade, the stability of the observed effects in studies on neural sexual responses has been rather neglected. AIMS: The current study aimed to test the stability of behavioral and neural responses to visual sexual stimuli in men and women over a time span of 1 to 1.5 years. To disentangle valence and arousal-related aspects of sexual stimulus processing, we employed not only sexual and neutral, but also positive and negative emotional stimuli. METHODS: A sample of 56 subjects (24 women) was assessed twice, with an interval of 1 to 1.5 years between assessments. During a functional magnetic resonance imaging (fMRI) session, participants passively viewed sexual, neutral, positive, and negative emotional pictures. Pictures were presented in 24 blocks of five pictures each. Every block was rated immediately after its presentation with respect to valence, arousal, and sexual arousal. MAIN OUTCOME MEASURES: Blood oxygen level dependent (BOLD) responses measured by fMRI and stimulus ratings. RESULTS: fMRI analyses revealed a distributed network involved in the processing of sexual stimuli, with large parts of this network being consistently activated at both assessment points. Nucleus accumbens, anterior cingulate, occipital and parietal cortex showed the most robust results with respect to group stability. Responses of anterior cingulate, orbitofrontal, parietal and occipital cortex showed interindividual stability. Gender differences were restricted to a few regions of interest. CONCLUSIONS: Our data indicate stability of neural responses toward sexual stimuli not only on the group but also on the individual level. Activation of parietal and occipital cortex might reflect a trait like character of attention related responses toward sexual stimuli. PMID- 25117820 TI - Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG 2100. AB - BACKGROUND: Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab induced hypertension. METHODS: A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG 5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160 mm Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3-5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100. RESULTS: When using the phenotype of SBP>160 mm Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 * 10(-8); OR=3.3) and in the cumulative dose model (P=4.7 * 10(-8); HR=2.2), respectively. Similar associations with rs6453204 were seen for CTC grade 3-5 hypertension but did not meet genome-wide significance. Validation study from ECOG-2100 demonstrated a statistically significant association between this SNP and grade 3/4 hypertension using the binary model (P-value=0.037; OR=2.4). CONCLUSIONS: A genetic variant in SV2C predicted clinically relevant bevacizumab-induced hypertension in two independent, randomised phase III trials. PMID- 25117826 TI - Person-to-person transmission of norovirus resulting in an outbreak of acute gastroenteritis at a summer camp. AB - BACKGROUND: A significant proportion of norovirus (NV) gastroenteritis outbreaks described in the Spanish literature have been because of contaminated food or water. AIM: This study describes an outbreak of acute gastroenteritis because of NV in which there was person-to-person transmission. MATERIALS AND METHODS: A retrospective cohort study was carried out; we established the case definition for primary and secondary cases. An epidemiological survey was designed, including possible food exposures, and clinical and laboratory data. Water and stool samples were taken from affected individuals and food handlers. The presence of NV was detected using a reverse transcription-PCR assay. We analyzed the risk of gastroenteritis using relative risk and its 95% confidence interval as the measure of association, and estimated the basic reproductive number (R0). RESULTS: The primary attack rate was 45.0%, with no significant differences between sexes. The secondary attack rate during the camp stay was 22.7%. The basic reproductive number for 5 days was R0=2.62. The most frequent symptoms were abdominal pain (85.7%) and vomiting (81.9%). Epidemiological analysis showed no association with food or drinking water. A total of 66.6% (8/12) of stool samples tested positive for NV (genogroup II). CONCLUSION: Control measures in general, and hand hygiene in particular, should be extended to the families once the children return home, to prevent secondary cases in NV outbreaks. PMID- 25117827 TI - Synthesis of novel carbazole based styryl: rational approach for photophysical properties and TD-DFT. AB - The synthesis and solvatochromic behavior of four novel carbazole based fluorescent styryl dyes were explained. In chlorinated solvents such as DCM and chloroform, these dyes show bathochromic shift in their absorption as well as emission. The styryl dyes 6b and 6c show solid state yellow fluorescence. DFT and TD-DFT computations were performed to study structural, molecular, electronic and photophysical properties of these dyes. The computed absorption and emission wavelength values are found to be in good agreement with the experimental results. The photophysical properties of these 1-styryl carbazole dyes are also compared with the recently reported 3-styrl carbazole dyes. The unique behavior of dye 6d is well explained by its optimized geometry found in the excited state. Ratio of ground to excited state dipole moment of the synthesized novel styryl compounds were calculated by Bakhshiev and Bilot-Kawski correlations. PMID- 25117828 TI - Synthesis, crystal structure and spectroscopic properties of a novel yttrium(III) fluoride dimolybdate(VI): YFMo2O7. AB - Thermal treatment of a mixture of Y2O3, YF3 and MoO3 in a 1 : 1 : 6 molar ratio at 850 degrees C in evacuated silica ampoules yielded colorless, platelet-shaped single crystals of YFMo2O7. SiO2 was dissolved from the ampoule wall in small amounts, but could be removed from the crude product by treatment with hydrofluoric acid (20%). The title compound crystallizes monoclinically in the space group P2/c with two formula units per unit cell with the dimensions a = 4.2609(2), b = 6.5644(4), c = 11.3523(7) A, and beta = 90.511(2) degrees . Its crystal structure contains crystallographically unique Y(3+) cations in a pentagonal bipyramidal environment consisting of two F(-) anions in the apical positions and five O(2-) anions in the equatorial positions. These polyhedra are connected to {[YFO](8-)} chains along [100] by sharing common F(-) vertices. The likewise crystallographically unique Mo(6+) cations exhibit a coordination number of five and reside in the centers of distorted square pyramids built up of oxide anions. These entities are fused to chains along [001] by sharing common edges and vertices according to {[MoOOO](-)}. Taking a sixth oxygen ligand further away from the Mo(6+) cations into account, the aforementioned chains assemble to corrugated {[MoOOO](-)} layers perpendicular to [010] with the {[YFO](8-)} chains situated between these sheets. Since Y(3+) represents a non-luminescent rare earth metal(iii) cation, YFMo2O7 is a suitable host material for doping with luminescence-active lanthanoid(iii) cations, such as Eu(3+). PMID- 25117825 TI - Eye movements in ephedrone-induced parkinsonism. AB - Patients with ephedrone parkinsonism (EP) show a complex, rapidly progressive, irreversible, and levodopa non-responsive parkinsonian and dystonic syndrome due to manganese intoxication. Eye movements may help to differentiate parkinsonian syndromes providing insights into which brain networks are affected in the underlying disease, but they have never been systematically studied in EP. Horizontal and vertical eye movements were recorded in 28 EP and compared to 21 Parkinson's disease (PD) patients, and 27 age- and gender-matched healthy subjects using standardized oculomotor tasks with infrared videooculography. EP patients showed slow and hypometric horizontal saccades, an increased occurrence of square wave jerks, long latencies of vertical antisaccades, a high error rate in the horizontal antisaccade task, and made more errors than controls when pro- and antisaccades were mixed. Based on oculomotor performance, a direct differentiation between EP and PD was possible only by the velocity of horizontal saccades. All remaining metrics were similar between both patient groups. EP patients present extensive oculomotor disturbances probably due to manganese induced damage to the basal ganglia, reflecting their role in oculomotor system. PMID- 25117829 TI - Species variation in the enantioselective metabolism of tegafur to 5-fluorouracil among rats, dogs and monkeys. AB - OBJECTIVES: Tegafur (FT), a pro-drug of 5-fluorouracil (5-FU), is a racemate consisting of two enantiomers, R and S-FT. The aim of this study was to clarify interspecies variation in the enantioselective metabolism of FT. METHODS: Plasma concentrations of FT enantiomers were determined in rats, dogs and monkeys following intravenous and oral dosing of the racemate (5 mg/kg). In addition, the enzymatic conversion of FT enantiomers to 5-FU was assayed using hepatic preparations. KEY FINDINGS: Metabolic clearance of R-FT was higher than that of S FT in rats and monkeys, but S-FT was the preferential substrate for dogs. An inhibition study revealed that cytochrome P450 is primarily responsible for the enantioselective metabolism of FT in rats and dogs. In contrast, in monkeys, thymidine phosphorylase was a determinant of the enantioselectivity in FT metabolism. Although oral bioavailability was not enantioselective, in-vitro and in-vivo kinetic studies suggested that the enantioselectivity in the hepatic intrinsic clearance of FT directly influences the body clearance in all animal species examined. CONCLUSIONS: The interspecies variations were observed in the enantioselective pharmacokinetics of FT, and the in-vivo enantioselectivity could be extrapolated from the in-vitro metabolic activities. PMID- 25117838 TI - Laparoscopic discoid anterior rectal excision with the circular stapler for rectosigmoid endometriosis, performed by the gynecologic surgeon. AB - STUDY OBJECTIVE: To demonstrate the technique of laparoscopic discoid anterior rectal wall resection using a circular stapler, feasible in the case of rectosigmoid endometriosis lesions measuring <= 3 cm. DESIGN: Case report (Canadian Task Force classification III). SETTING: Private practice hospital in Sao Paulo, Brazil. PATIENT: Thirty-four-year-old woman with pelvic deep endometriosis including a 2-cm lesion in the rectosigmoid situated 11 cm proximally to the anal border. She had chronic pelvic pain, dysmenorrhea, dyspareunia, and constipation. She had undergone no previous surgical procedures. INTERVENTIONS: Standard 4-puncture laparoscopy was performed, and all visible endometriosis lesions were first removed before proceeding to rectal resection. The avascular rectovaginal space was identified, and the rectosigmoid was mobilized cranially, releasing the vagina and increasing the final distance of the bowel anastomosis to the anal border. The rectosigmoid nodule was isolated in its entire circumference and remained restricted to the anterior wall of the bowel. It was then transfixed using a 2-0 polyglycolic suture, with the healthy proximal and distal limits of the bowel included in the suture. A 33-cm endoscopic circular stapler was introduced via the anus up to the distal limit of the lesion and opened inside the bowel lumen. By pulling the edges of the suture, the rectosigmoid nodule was introduced inside of the circular stapler. It was fired to resect the anterior rectal wall, and the anastomosis was situated at the anterior and lateral walls of the bowel. Integrity of the bowel was checked via infusion of saline solution with methylene blue dye. Gynecologic surgeons performed all of the procedures. MEASUREMENTS AND MAIN RESULTS: Bowel resection took 20 minutes, and the entire surgical procedure lasted 120 minutes. The patient was discharged after 48 hours. There were no intercurrent events, either early or late postoperatively. The patient was symptom-free at 2 years of follow up. CONCLUSION: Laparoscopic discoid excision of an anterior rectal nodule using the circular stapler is an effective option for treating selected cases of rectosigmoid endometriosis. The technique might be reproducible by gynecologic surgeons after proper training. PMID- 25117839 TI - Fertility-preserving management of a uterine arteriovenous malformation: a case report of uterine artery embolization (UAE) followed by laparoscopic resection. AB - Herein is presented a fertility-preserving approach in the management of a uterine arteriovenous malformation (AVM) resistant to endovascular management. The patient had a documented AVM and underwent 2 uterine artery embolization procedures, with subsequent recurrence of symptoms. Doppler ultrasound demonstrated recanalization of the AVM. Ultimately, laparoscopic resection of the AVM was performed after laparoscopic ligation of the uterine arteries. Postoperatively, the patient has remained asymptomatic. Laparoscopic resection of a uterine AVM may offer a fertility-preserving alternative to hysterectomy in patients in whom endovascular management has failed. PMID- 25117830 TI - Pax6 is essential for the maintenance and multi-lineage differentiation of neural stem cells, and for neuronal incorporation into the adult olfactory bulb. AB - The paired type homeobox 6 (Pax6) transcription factor (TF) regulates multiple aspects of neural stem cell (NSC) and neuron development in the embryonic central nervous system. However, less is known about the role of Pax6 in the maintenance and differentiation of adult NSCs and in adult neurogenesis. Using the +/Sey(Dey) mouse, we have analyzed how Pax6 heterozygosis influences the self-renewal and proliferation of adult olfactory bulb stem cells (aOBSCs). In addition, we assessed its influence on neural differentiation, neuronal incorporation, and cell death in the adult OB, both in vivo and in vitro. Our results indicate that the Pax6 mutation alters Nestin(+)-cell proliferation in vivo, as well as self renewal, proliferation, and survival of aOBSCs in vitro although a subpopulation of +/Sey(Dey) progenitors is able to expand partially similar to wild-type progenitors. This mutation also impairs aOBSC differentiation into neurons and oligodendrocytes, whereas it increases cell death while preserving astrocyte survival and differentiation. Furthermore, Pax6 heterozygosis causes a reduction in the variety of neurochemical interneuron subtypes generated from aOBSCs in vitro and in the incorporation of newly generated neurons into the OB in vivo. Our findings support an important role of Pax6 in the maintenance of aOBSCs by regulating cell death, self-renewal, and cell fate, as well as in neuronal incorporation into the adult OB. They also suggest that deregulation of the cell cycle machinery and TF expression in aOBSCs which are deficient in Pax6 may be at the origin of the phenotypes observed in this adult NSC population. PMID- 25117840 TI - Laparoscopic myomectomy: clinical outcomes and comparative evidence. AB - Laparoscopic myomectomy is a common surgical treatment for symptomatic uterine leiomyomas. Proponents of the laparoscopic approach to myomectomy propose that the advantages include shorter length of hospital stay and recovery time. Others suggest longer operative time, greater blood loss, increased risk of recurrence, risk of uterine rupture in future pregnancies, and potential dissemination of cells with use of morcellation. This review outlines techniques for performance of laparoscopic myomectomy and critically appraises the available evidence for operative data, short-term and long-term complications, and reproductive outcomes. PMID- 25117841 TI - Is the Allen Masters defect the most misunderstood lesion in gynecology? PMID- 25117842 TI - The knowledge of uterine mullerian anomalies, of the pelvic female anatomy and of the physics of ultrasounds is the basic starting point to differentiate between septate and bicornuate uteri. PMID- 25117843 TI - Are experiences of sexual violence related to special needs in patients with substance use disorders? A study in opioid-dependent patients. AB - A history of sexual violence has been related to more complex treatment needs in patients with substance use disorders (SUD). Most of the existing studies, however, included patients with various types of SUD, did not examine gender differences and focused on a small range of clinical domains. Our sample consisted of opioid-dependent outpatients treated during a three-year period in a German metropolitan region. The analysis was based on a local case register and included all patients for whom information on lifetime sexual violence was available (N=3531; 68.3% males). In a case-control design, patients with a history of sexual violence were compared to patients without these experiences regarding a wide range of clinical and social factors indicative of potential needs. Almost two thirds (65.6%) of the female patients and 10.9% of the males reported experiences of sexual violence. Victims differed from non-victims across a variety of domains, including more psychiatric symptoms and suicide attempts, more legal problems, financial and family problems, as well as a higher use of services. In contrast to a previous study among alcohol-dependent patients, no gender differences became apparent. Our findings suggest that experiences of sexual violence are an indicator for more complex needs in opioid-dependent patients of both genders. In addition to integrated trauma-informed approaches, an effort needs to be made to link addiction facilities to further institutions to meet these complex needs. PMID- 25117845 TI - A latent growth curve analysis of alcohol-use specific parenting and adolescent alcohol use. AB - This study investigates how changes in alcohol use-specific parenting were associated with adolescent drinking trajectories. Three waves of data from a longitudinal study investigating adolescent substance use were used. The community sample (N=378) was aged 10-13 at the first wave of assessment. Our findings show that over time, parents are less likely to discipline their adolescents' drinking, more likely to grant their adolescent permission to drink, and less likely to communicate the consequences of alcohol use. Moreover, these changes are associated with escalation in adolescent alcohol use. Parental efficacy at preventing alcohol use declined, but did not relate to changes in adolescent drinking. PMID- 25117844 TI - Curiosity predicts smoking experimentation independent of susceptibility in a US national sample. AB - PURPOSE: To improve smoking prevention efforts, better methods for identifying at risk youth are needed. The widely used measure of susceptibility to smoking identifies at-risk adolescents; however, it correctly identifies only about one third of future smokers. Adding curiosity about smoking to this susceptibility index may allow us to identify a greater proportion of future smokers while they are still pre-teens. METHODS: We use longitudinal data from a recent national study on parenting to prevent problem behaviors. Only oldest children between 10 and 13years of age were eligible. Participants were identified by RDD survey and followed for 6years. All baseline never smokers with at least one follow-up assessment were included (n=878). The association of curiosity about smoking with future smoking behavior was assessed. Then, curiosity was added to form an enhanced susceptibility index and sensitivity, specificity and positive predictive value were calculated. RESULTS: Among committed never smokers at baseline, those who were 'definitely not curious' were less likely to progress toward smoking than both those who were 'probably not curious' (ORadj=1.89; 95% CI=1.03-3.47) or 'probably/definitely curious' (ORadj=2.88; 95% CI=1.11-7.45). Incorporating curiosity into the susceptibility index increased the proportion identified as at-risk to smoke from 25.1% to 46.9%. The sensitivity (true positives) for this enhanced susceptibility index for both experimentation and established smoking increased from 37-40% to over 50%, although the positive predictive value did not improve. CONCLUSION: The addition of curiosity significantly improves the identification and classification of which adolescents will experiment with smoking or become established smokers. PMID- 25117846 TI - Hardcore smokers: what do we know? AB - AIMS: The existence of smokers who are resistant to smoking cessation treatment has long been noted in the literature. There has been ongoing debate as to whether the proportion of these smokers is increasing as smoking prevalence rates stagnate. Studies define hardcore smokers inconsistently and within the context of specific illnesses, addiction, population, and/or theoretical paradigms. This review examines the existing literature related to hardcore smokers to develop a better understanding of what is known and not known about this group to guide smoking cessation treatment. METHODS: PubMed MESH search and review of research publications from 1998 to 2012 (N=61). RESULTS: Inconsistent definitions of hardcore smoking make it difficult to estimate prevalence rates and to identify specific characteristics of persistent smokers. Generally, persistent smokers have higher levels of nicotine dependence, are disproportionately from lower socioeconomic groups, start smoking at an earlier age, and are more likely to have a psychological co-morbidity. DISCUSSION: Defining some smokers as hardcore is limiting. Targeted and tailored interventions for smoking cessation for persistent smoking have demonstrated effectiveness in a small number of studies. Treatment access barriers need to be addressed to improve the reach and effectiveness of cessation with persistent smokers. Efforts to limit early age initiation of tobacco use are a critical element in averting persistent smoking. PMID- 25117847 TI - Problem gambling and family violence: prevalence and patterns in treatment seekers. AB - The primary aim of this study was to explore the prevalence and patterns of family violence in treatment-seeking problem gamblers. Secondary aims were to identify the prevalence of problem gambling in a family violence victimisation treatment sample and to explore the relationship between problem gambling and family violence in other treatment-seeking samples. Clients from 15 Australian treatment services were systematically screened for problem gambling using the Brief Bio-Social Gambling Screen and for family violence using single victimisation and perpetration items adapted from the Hurt-Insulted-Threatened Screamed (HITS): gambling services (n=463), family violence services (n=95), alcohol and drug services (n=47), mental health services (n=51), and financial counselling services (n=48). The prevalence of family violence in the gambling sample was 33.9% (11.0% victimisation only, 6.9% perpetration only, and 16.0% both victimisation and perpetration). Female gamblers were significantly more likely to report victimisation only (16.5% cf. 7.8%) and both victimisation and perpetration (21.2% cf. 13.0%) than male gamblers. There were no other demographic differences in family violence prevalence estimates. Gamblers most commonly endorsed their parents as both the perpetrators and victims of family violence, followed by current and former partners. The prevalence of problem gambling in the family violence sample was 2.2%. The alcohol and drug (84.0%) and mental health (61.6%) samples reported significantly higher rates of any family violence than the gambling sample, while the financial counselling sample (10.6%) reported significantly higher rates of problem gambling than the family violence sample. The findings of this study support substantial comorbidity between problem gambling and family violence, although this may be accounted for by a high comorbidity with alcohol and drug use problems and other psychiatric disorders. They highlight the need for routine screening, assessment and management of problem gambling and family violence in a range of services. PMID- 25117848 TI - Environmental tobacco smoke exposure among smokers and non-smokers receiving outpatient substance abuse treatment. AB - INTRODUCTION: Environmental Tobacco Smoke (ETS) has been linked to numerous health problems. While research has demonstrated high prevalence of tobacco use among individuals receiving treatment for substance use disorders (SUDs), no studies have examined ETS among individuals receiving treatment for SUDs, paying specific attention to non-smokers who may be at risk for high exposure to ETS. METHODS: Participants (N=261) enrolled in outpatient substance abuse treatment completed a survey, in which 14 items were used to quantify ETS exposure and smoking policies across several environments. RESULTS: Among smokers, 85% reported that their significant others also smoked as compared to 15% among non smokers (chi(2)=6.624, p<.05). A logistic regression examined the characteristics that predicted smoking in the home. The overall model was significant, (chi(2)=36.046, p<.0005) with variables that independently predicted smoking in the home included having less than a high school diploma, being female, and living with a smoker. Income, age, and living with children were not found to be significant. Overall, 42% white collar workers 26% of service workers and 30% of blue collar workers reported no exposure to ETS. Sixty-seven percent of smokers strongly agreed or agreed that the hazards of secondhand smoke have been clearly demonstrated versus 58% of non-smokers. CONCLUSIONS: Smokers and non-smokers enrolled in outpatient substance abuse treatment are frequently exposed to ETS at home, work, and in social settings. The dangers of ETS should be addressed among this population through education, smoke-free policies, and cessation resources, with help from their treatment facility. PMID- 25117849 TI - Negative affect is associated with alcohol, but not cigarette use in heavy drinking smokers. AB - Co-use of alcohol and cigarettes is highly prevalent, and heavy drinking smokers represent a large and difficult-to-treat subgroup of smokers. Negative affect, including anxiety and depressive symptomatology, has been associated with both cigarette and alcohol use independently, but less is known about the role of negative affect in heavy drinking smokers. Furthermore, while some studies have shown negative affect to precede substance use, a precise biobehavioral mechanism has not been established. The aims of the present study were twofold. First, to test whether negative affect is associated with alcohol and cigarette use in a large community sample of heavy drinking smokers (n=461). And second, to examine craving as a plausible statistical mediator of the association between negative affect and alcohol and/or cigarette use. Hypothesis testing was conducted using a structural equation modeling approach with cross-sectional data. Analysis revealed a significant main effect of negative affect on alcohol use (beta=0.210, p<0.05), but not cigarette use (beta=0.131, p>0.10) in this sample. Mediational analysis revealed that alcohol craving was a full statistical mediator of this association (p<0.05), such that there was no direct association between negative affect and alcohol use after accounting for alcohol craving. These results are consistent with a negative reinforcement and relief craving models of alcohol use insofar as the experience of negative affect was associated with increased alcohol use, and the relationship was statistically mediated by alcohol craving, presumably to alleviate negative affect. Further longitudinal or experimental studies are warranted to enhance the causal inferences of this mediated effect. PMID- 25117850 TI - Differences between abstinent and non-abstinent individuals in recovery from alcohol use disorders. AB - OBJECTIVE: Non-abstinent goals can improve quality of life (QOL) among individuals with alcohol use disorders (AUDs). However, prior studies have defined "recovery" based on DSM criteria, and thus may have excluded individuals using non-abstinent techniques that do not involve reduced drinking. Furthermore, no prior study has considered length of time in recovery when comparing QOL between abstinent and non-abstinent individuals. The current aims are to identify correlates of non-abstinent recovery and examine differences in QOL between abstainers and non-abstainers accounting for length of time in recovery. SAMPLE: A large (N=5380) national sample of individuals who self-describe as "in recovery" from alcohol problems recruited in the context of the What Is Recovery? (WIR) study. METHOD: Multivariate stepwise regressions estimating the probability of non-abstinent recovery and average quality of life. RESULTS: Younger age (OR=0.72), no prior treatment (OR=0.63) or AA (OR=0.32), fewer dependence symptoms (OR=0.17) and less time in recovery all significantly (P<0.05) related to non-abstinent recovery. Abstainers reported significantly (P<0.05) higher QOL than non-abstainers (B=0.39 for abstinence vs. non-abstinence), and abstinence was one of the strongest correlates of QOL, even beyond sociodemographic variables like education. CONCLUSIONS: Non-abstainers are younger with less time in recovery and less problem severity but worse QOL than abstainers. Clinically, individuals considering non-abstinent goals should be aware that abstinence may be best for optimal QOL in the long run. Furthermore, time in recovery should be accounted for when examining correlates of recovery. PMID- 25117851 TI - Methadone maintenance treatment may improve completion rates and delay opioid relapse for opioid dependent individuals under community corrections supervision. AB - AIMS: Several studies have demonstrated the importance of agonist therapies such as methadone and buprenorphine for preventing relapse for individuals being released from jail or prison to the community. No studies have examined the impact of methadone for increasing the completion of community supervision requirements and preventing opioid relapse for individuals under community corrections supervision. This observational study compared the community corrections completion rate and opioid relapse rate of individuals receiving methadone maintenance therapy (MMT) to individuals who did not. METHODS: Of the 2931 individuals enrolled under criminal justice supervision in the community, Treatment Accountability for Safer Communities (TASC), and who met criteria for opioid dependence, 329 (11%) individuals reported receiving MMT in the community. RESULTS: The majority of participants were White (79.8%) and male (63.5%), with a mean age of 31.33years (SD=9.18), and were under supervision for 10.4months (SD=9.1). MMT participants were less likely to fail out of supervision compared to individuals not in MMT (39.0% vs. 52.9%, p<0.001), and had a lower rate of relapse (32.9%) and longer time to relapse (average days=89.7, SD=158.9) compared to the relapse rate (55.9%) and time to relapse (average days=60.5, SD=117.9) of those not on MMT. CONCLUSIONS: While the observational nature of this study prevents causal inferences, these results suggest that utilization of MMT in community corrections may increase the likelihood of completing supervision requirements and delay time to opioid relapse. Providing agonist therapies to opioid dependent individuals under supervision appears to be a critical strategy in this important population. PMID- 25117853 TI - Population dose-response analysis of daily seizure count following vigabatrin therapy in adult and pediatric patients with refractory complex partial seizures. AB - Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T) and is used as an adjunctive therapy for adult patients with refractory complex partial seizures (rCPS). The purpose of this investigation was to describe the relationship between vigabatrin dosage and daily seizure rate for adults and children with rCPS and identify relevant covariates that might impact seizure frequency. This population dose-response analysis used seizure-count data from three pediatric and two adult randomized controlled studies of rCPS patients. A negative binomial distribution model adequately described daily seizure data. Mean seizure rate decreased with time after first dose and was described using an asymptotic model. Vigabatrin drug effects were best characterized by a quadratic model using normalized dosage as the exposure metric. Normalized dosage was an estimated parameter that allowed for individualized changes in vigabatrin exposure based on body weight. Baseline seizure rate increased with decreasing age, but age had no impact on vigabatrin drug effects after dosage was normalized for body weight differences. Posterior predictive checks indicated the final model was capable of simulating data consistent with observed daily seizure counts. Total normalized vigabatrin dosages of 1, 3, and 6 g/day were predicted to reduce seizure rates 23.2%, 45.6%, and 48.5%, respectively. PMID- 25117854 TI - Combined electrical and global markers of dyssynchrony predict clinical response to cardiac resynchronization therapy. AB - AIM: To assess potential additional value of global left ventricular (LV) dyssynchrony markers in predicting cardiac resynchronization therapy (CRT) response in heart failure (HF) patients. METHODS: We included 103 HF patients (mean age 67 +/- 12 years, 83% male) who fulfilled the guidelines criteria for CRT treatment. All patients had undergone full clinical assessment, NT-proBNP and echocardiographic examination. Global LV dyssynchrony was assessed using total isovolumic time (t-IVT) and Tei index. On the basis of reduction in the NYHA class after CRT, patients were divided into responders and non-responders. RESULTS: Prolonged t-IVT [0.878 (range, 0.802-0.962), p = 0.005], long QRS duration [0.978 (range, 0.960-0.996), p = 0.02] and high tricuspid regurgitation pressure drop [1.047 (range, 1.001-1.096), p = 0.046] independently predicted response to CRT. A t-IVT >= 11.6 s/min was 67% sensitive and 62% specific (AUC 0.69, p = 0.001) in predicting CRT response. Respective values for a QRS >= 151 ms were 66% and 62% (AUC 0.65, p = 0.01). Combining the two variables had higher specificity (88%) in predicting CRT response. In atrial fibrillation (AF) patients, only prolonged t-IVT [0.690 (range, 0.509-0.937), p = 0.03] independently predicted CRT response. CONCLUSION: Combining prolonged t-IVT and the conventionally used broad QRS duration has a significantly higher specificity in identifying patients likely to respond to CRT. Moreover, in AF patients, only prolonged t-IVT independently predicted CRT response. PMID- 25117852 TI - At-Risk/Problematic Shopping and Gambling in Adolescence. AB - Elevated levels of both pathological gambling (PG) and problem shopping (PS) have been reported among adolescents, and each is associated with a range of other negative health/functioning measures. However, relationships between PS and PG, particularly during adolescence, are not well understood. In this study, we explored the relationship between different levels of problem-gambling severity and health/functioning characteristics, gambling-related social experiences, gambling behaviors and motivations among adolescents with and without at risk/problematic shopping (ARPS). Survey data from Connecticut high school students (n = 2,100) were analyzed using bivariate analyses and logistic regression modeling. Although at-risk/problematic gambling (ARPG) was not increased among adolescents with ARPS, adolescents with ARPG (vs non-gamblers) were more likely to report having experienced a growing tension or anxiety that could only be relieved by shopping and missing other obligations due to shopping. In comparison to the non-ARPS group, a smaller proportion of respondents in the ARPS group reported paid part-time employment, whereas a greater proportion of respondents reported excessive gambling by peers and feeling concerned over the gambling of a close family member. In general, similar associations between problem-gambling severity and measures of health/functioning and gambling-related behaviors and motivations were observed across ARPS and non-ARPS adolescents. However, associations were weaker among ARPS adolescents for several variables: engagement in extracurricular activities, alcohol and caffeine use and gambling for financial reasons. These findings suggest a complex relationship between problem-gambling severity and ARPS. They highlight the importance of considering co-occurring risk behaviors such as ARPS when treating adolescents with at risk/problem gambling. PMID- 25117855 TI - Examination of spatiotemporal gait parameters during the 6-min walk in individuals with multiple sclerosis. AB - This investigation examined spatiotemporal parameters of gait during the 6-min walk (6MW) in individuals with multiple sclerosis (MS) and in healthy controls. Eighteen individuals with MS [divided into those who were independently ambulatory (n=10) and those who were ambulatory with assistance (n=8)] and 10 healthy controls performed a 6MW while recording spatiotemporal gait parameters using a pressure-sensitive walkway. Parameters recorded were walking velocity, cadence, step length and width, step time, percent of the gait cycle in double support, and variability of step length and width, step time, and double support. The ambulatory with assistance MS group had a significantly greater reduction in walking velocity (P=0.000) over the course of the 6MW, which coincided with a significantly greater increase in step time and double support (P=0.029) than in the other groups. Only the ambulatory with assistance MS group showed an increase in step-time variability and double-support variability during the 6MW (P's<0.05). The novel results indicate that the reduction in velocity over prolonged walking occurs through a greater change in the temporal parameters of gait in persons with MS who require assistance while walking. In addition, the increase in gait variability in the individuals with MS who require assistance while walking indicates that the control over walking further deteriorates over the course of the 6MW. PMID- 25117856 TI - Adherence to evidence based care practices for childbirth before and after a quality improvement intervention in health facilities of Rajasthan, India. AB - BACKGROUND: After the launch of Janani Suraksha Yojana, a conditional cash transfer scheme in India, the proportion of women giving birth in institutions has rapidly increased. However, there are important gaps in quality of childbirth services during institutional deliveries. The aim of this intervention was to improve the quality of childbirth services in selected high caseload public health facilities of 10 districts of Rajasthan. This intervention titled "Parijaat" was designed by Action Research & Training for Health, in partnership with the state government and United Nations Population Fund. METHODS: The intervention was carried out in 44 public health facilities in 10 districts of Rajasthan, India. These included district hospitals (9), community health centres (32) and primary health centres (3). The main intervention was orientation training of doctors and program managers and regular visits to facilities involving assessment, feedback, training and action. The adherence to evidence based practices before, during and after this intervention were measured using structured checklists and scoring sheets. Main outcome measures included changes in practices during labour, delivery or immediate postpartum period. RESULTS: Use of several unnecessary or harmful practices reduced significantly. Most importantly, proportion of facilities using routine augmentation of labour reduced (p = 0), episiotomy for primigravidas (p = 0.0003), fundal pressure (p = 0.0003), and routine suction of newborns (0 = 0.0005). Among the beneficial practices, use of oxytocin after delivery increased (p = 0.0001) and the practice of listening foetal heart sounds during labour (p = 0.0001). Some practices did not show any improvements, such as dorsal position for delivery, use of partograph, and hand-washing. CONCLUSIONS: An intervention based on repeated facility visits combined with actions at the level of decision makers can lead to substantial improvements in quality of childbirth practices at health facilities. PMID- 25117858 TI - [Reconciling activities of working women providing care and the influence of structural and cultural factors]. AB - BACKGROUND: Today, an increasing proportion of society has to reconcile eldercare and work. This task poses challenges for them, which they meet through an adjustment of their everyday living arrangements. These coping strategies have been so far scarcely noted within research on the reconciliation of elder care and employment. Knowledge about the active dealing with this parallel involvement in both spheres of life is of vital importance when wanting to derive precisely tailored support measures for employed care givers. MATERIALS AND METHODS: A goal of this article is to deliver insight on reconciling activities of employed women who provide care, while it tries to specify respective factors which determine those actions. Moreover, an ideal typology is presented, which systematizes these associations. RESULTS: With this ideal typology, conceptual instruments have been developed which illustrate the complex reality of the reconciliation actions and the dependence on various coping resources. In gerontological practice, these findings may provide support to design an intervention strategy tailored to the individual situation that addresses the everyday level of action and strengthens the performance of those affected. PMID- 25117857 TI - [Sleep and sleep disorders in the elderly: Part 1: epidemiology and diagnostics]. AB - Restorative sleep is an important factor for well-being, performance and quality of life. The basic diagnostic procedure of a sleep disorder is to take a comprehensive sleep history. Sleep disorders can and must be distinguished from the physiological changes of sleep in the elderly. Insomnia (difficulty in sleeping), daytime sleepiness (hypersomnia), sleep-related breathing disorders (SRBD) and movement disorders during sleep are also common in the elderly. They must be detected because they are treatable and can dominate the clinical picture of geriatric syndromes. Nursing home residents and dementia patients are in particular need of attention as their sleep is often adversely affected by the living environment and the daily institutional routine. PMID- 25117859 TI - The emerging trend of work beyond retirement age in Germany. Increasing social inequality? AB - BACKGROUND: Population ageing, demographic change and the financial crisis has put the financial sustainability of the German pension system at risk. In reaction to these challenges, Germany recently abandoned generous early retirement policies and moved towards policies encouraging higher employment among the elderly. OBJECTIVES: In this article we evaluate how these labour market and pension policies affected the retirement decisions of older workers in Germany over the last three decades. Complementing previous research on early retirement, we focus in particular on those working past the mandatory retirement age of 65 years and examine whether the composition of this group of postretirement-age workers has changed over time. DATA AND METHODS: We analyse pooled cross-sectional data from three rounds of the German Ageing Survey which allow us to cover the last three decades from 1980 to 2008. Estimating multinomial logit models we distinguish explanatory factors on the individual, organizational and institutional level that frame the decision to leave the labour market before the age of 65, to stop working at 65 or to work past 65. RESULTS: Over the last three decades, the share of German workers leaving the labour market after the mandatory retirement age of 65 has increased markedly. This trend towards working longer has changed particularly among the low educated workforce which in previous decades traditionally has exhibited a tendency to retire early. In contrast to high-skilled workers, the decision to work longer among low-educated workers is mainly driven by financial need (and is usually not in line with their desire or their ability to work for longer). CONCLUSION: Our findings suggest an increase in social inequality in retirement decisions as a result of the policy shift towards activation. We conclude by arguing for a more fine-grained understanding of the reasons why people work longer. Such research would provide valuable insights into how to design future labour market and pension reforms preventing a rise in social inequalities. PMID- 25117860 TI - [Aged skin and skin care]. AB - BACKGROUND: Aged skin is the sum of chronological und UV-induced aging. Light exposed skin is unattractive, with irregular pigmentation, roughness und scaliness. The skin is often dry and itches. METHODS: The present paper provides an overview of diseases of aging skin and describes how to prevent or reduce disease by prophylactic and therapeutic skin care. RESULTS: Aged skin can develop into several skin diseases, e.g., different types of eczema and skin cancer. In the body folds we often find an irritant contact eczema caused by friction from skin to skin, sweating, and urinary and fecal incontinence. In the bedridden, bed sores can also develop. Furthermore, there is a delay in wound healing owing to old age. Use of adequate creams and ointments is very helpful in preventing and improving most skin diseases of mature skin. However, the knowledge of aged people and healthcare professionals about the importance of skin care is low. Older people are often unable to care for their skin because they are lacking the physical and mental ability. CONCLUSION: Healthcare professionals are not sufficiently trained about the value of proper skin care. Adequate studies on the role of skin care and selection of the correct preparation in various aged related diseases are lacking. PMID- 25117861 TI - Dysfunctional sexual beliefs: a comparative study of heterosexual men and women, gay men, and lesbian women with and without sexual problems. AB - INTRODUCTION: Conservative and dysfunctional sexual beliefs are commonly associated with sexual problems among heterosexual men and women. However, little is known about the role of sexual beliefs in sexual problems in gay men and lesbians. AIM: The present study aimed at analyzing the role of sexual beliefs in sexual dysfunction in a sample of heterosexual and homosexual men and women. MAIN OUTCOME MEASURES: Participants answered questions about self-perceived sexual problems and completed the Sexual Dysfunctional Beliefs Questionnaire. METHODS: Two hundred twelve men (106 gay) and 192 women (96 lesbian) completed a Web survey. RESULTS: Findings indicated that men with sexual dysfunction (regardless of sexual orientation) reported significantly more conservative beliefs and more erroneous beliefs related to partner's sexual satisfaction compared with sexually healthy men. Also, gay men with sexual dysfunction (but not heterosexual men) scored higher on belief in sex as an abuse of men's power compared with healthy controls. In addition, heterosexual men scored higher on "macho" beliefs, beliefs regarding partner's sexual satisfaction, and partner's power, compared with gay men. For women, a main effect was found for sexual orientation, with lesbian women scoring higher on sexual desire as a sin, age-related beliefs, and affection primacy and lower on beliefs related to motherhood primacy. CONCLUSIONS: Overall, findings suggest that dysfunctional sexual beliefs may play a role as vulnerability factors for sexual dysfunction regardless of sexual orientation, particularly in men. PMID- 25117863 TI - Chronic renal disease and risk of cardiovascular morbidity-mortality. AB - The pathogenesis of cardiovascular disease in CKD differs subtly from that of non CKD patients. As renal function declines, the role and impact of treating classical risk factors may change and diminish. However, hypertension, hypercholesterolaemia and smoking cessation management should be optimized and may require multiple agents and approaches, particularly as CKD advances. Hypertension treatment would appear to be one management area in which performance is less than ideal. Moreover there are mechanisms and risk factors that are specific to CKD, capable of triggering a vascular pathology and that justify the surplus of CV morbidity in CKD patients and that require we consider CKD as a CV risk factor per se. In the initial stages of CKD it would be advisable to implement all the preventative measures to stem the onset of CV disease, whereas in the more advanced stages a multifactorial approach is likely to be necessary, as we have learned from the STENO-study within the diabetes. PMID- 25117862 TI - The dUTPase-related gene of bovine immunodeficiency virus is critical for viral replication, despite the lack of dUTPase activity of the encoded protein. AB - BACKGROUND: Deoxyuridine 5'-triphosphate nucleotide-hydrolases (dUTPases) are essential for maintaining low intra-cellular dUTP/dTTP ratios. Therefore, many viruses encode this enzyme to prevent dUTP incorporation into their genomes instead of dTTP. Among the lentiviruses, the non-primate viruses express dUTPases. In bovine immunodeficiency virus (BIV), the putative dUTPase protein is only 74 residues-long, compared to ~130 residues in other lentiviruses. RESULTS: In this study, the recombinant BIV dUTPase, as well as infectious wild-type (WT) BIV virions, were shown to lack any detectable dUTPase activity. Controls of recombinant dUTPase from equine infectious anemia virus (EIAV) or of EIAV virions showed substantial dUTPase activities. To assess the importance of the dUTPase to BIV replication, we have generated virions of WT BIV or BIV with mutations in the dUTPase gene. The two mutant viral dUTPases were the double mutant D48E/N57S (in the putative enzyme active site and its vicinity) and a deletion of 36 residues. In dividing Cf2Th cells and under conditions where the WT virus was infectious and generated progeny virions, both mutant viruses were defective, as no progeny viruses were generated. Analyses of the integrated viral cDNA showed that cells infected with the mutant virions carry in their genomic DNA levels of integrated BIV DNA that are comparable to those in WT BIV-infected cells. CONCLUSIONS: The herby presented results show that the two BIV mutants with the modified dUTPase gene could infect cells, as viral cDNA was synthesized and integrated into the host cell DNA. However, no virions were generated by cells infected by these mutants. The most likely explanation is that either the integrated cDNA of the mutants is defective (due to potential multiple mutations, introduced during reverse-transcription) or that the original dUTPase mutations have led to severe blocks in viral replication at steps post integration. These results emphasize the importance of the dUTPase-related sequence to BIV replication, despite the lack of any detectable catalytic activity. PMID- 25117864 TI - Uliginosin B, a natural phloroglucinol derivative, presents a multimediated antinociceptive effect in mice. AB - OBJECTIVE: Investigate the involvement of monoaminergic and glutamatergic systems on the antinociceptive and ataxic effects of uliginosin B, which we have already demonstrated to be a promising molecular scaffold to develop new analgesic drugs. METHODS: Uliginosin B was obtained from hexane extract of aerial parts of Hypericum polyanthemum by chromatographic methods. Uliginosin B antinociceptive and motor coordination effects were evaluated in mice by using hot-plate (15 and 90 mg/kg, i.p.) and rotarod (90 mg/kg, i.p.) tests, respectively. The mechanism of action was investigated through pretreatments with prazosin 1 mg/kg intraperitoneal (alpha1 receptor antagonist), yohimbine 5 mg/kg intraperitoneal (alpha2 receptor antagonist), pCPA 300 mg/kg intraperitoneal (serotonin synthesis inhibitor) and MK-801 0.25 mg/kg intraperitoneal (N-methyl-D-aspartic acid receptor antagonist). KEY FINDINGS: The antinociceptive effect of uliginosin B (15 and 90 mg/kg, i.p.) was reduced significantly by pCPA and MK-801. Prazosin and yohimbine improved the antinociceptive effect of the highest dose (90 mg/kg, i.p.) of uliginosin B only. The ataxic effect of uliginosin B (90 mg/kg, i.p.) was completely prevented by pretreatment with pCPA or MK-801, but it was unaffected by pretreatment with prazosin or yohimbine. CONCLUSION: These data confirm the contribution of monoaminergic neurotransmission as well as provide the first evidence of glutamatergic neurotransmission contribution to the uliginosin B effects. PMID- 25117865 TI - Airway complications in traumatic lower cervical spinal cord injury: A retrospective study. AB - OBJECTIVE: To investigate risk factors for pneumonia in patients with traumatic lower cervical spinal cord injury. DESIGN: Observational study, retrospective study. SETTING: Spinal cord unit in a maximum care hospital. METHODS: Thirty seven patients with acute isolated traumatic spinal cord injury at levels C4-C8 and complete motor function injury (AIS A, B) treated from 2004 to 2010 met the criteria for inclusion in our retrospective analysis. The following parameters were considered: ventilation-specific parameters, re-intubation, creation of a tracheostomy, pneumonia, antibiotic treatment, and length of intensive care unit (ICU) stay and total hospitalization. RESULTS: Among the patients, 81% had primary invasive ventilation. In 78% of cases a tracheostomy was created; 3% of these cases were discharged with invasive ventilation and 28% with a tracheostomy without ventilation. Pneumonia according to Centers for Disease Control criteria occurred in 51% of cases within 21+/-32 days of injury, and in 3% at a later date. The number of pre-existing conditions was significantly associated with pneumonia. Length of ICU stay was 25+/-34 days, and average total hospital duration was 230+/-144 days. Significant factors affecting the duration of ventilation were the number of pre-existing conditions and tetraplegia-specific complications. CONCLUSIONS: Our results confirm that patients with traumatic lower cervical spinal cord injuries defined by lesion level and AIS constitute a homogeneous group. This group is characterized by a high rate of pneumonia during the first 4 weeks after injury. The number of pre-existing general conditions and spinal injury-specific comorbidities are the only risk factors identified for the development of pneumonia and/or duration of ventilation. PMID- 25117871 TI - Effects of the racket polar moment of inertia on dominant upper limb joint moments during tennis serve. AB - This study examined the effect of the polar moment of inertia of a tennis racket on upper limb loading in the serve. Eight amateur competition tennis players performed two sets of 10 serves using two rackets identical in mass, position of center of mass and moments of inertia other than the polar moment of inertia (0.00152 vs 0.00197 kg.m2). An eight-camera motion analysis system collected the 3D trajectories of 16 markers, located on the thorax, upper limbs and racket, from which shoulder, elbow and wrist net joint moments and powers were computed using inverse dynamics. During the cocking phase, increased racket polar moment of inertia was associated with significant increases in the peak shoulder extension and abduction moments, as well the peak elbow extension, valgus and supination moments. During the forward swing phase, peak wrist extension and radial deviation moments significantly increased with polar moment of inertia. During the follow-through phase, the peak shoulder adduction, elbow pronation and wrist external rotation moments displayed a significant inverse relationship with polar moment of inertia. During the forward swing, the magnitudes of negative joint power at the elbow and wrist were significantly larger when players served using the racket with a higher polar moment of inertia. Although a larger polar of inertia allows players to better tolerate off-center impacts, it also appears to place additional loads on the upper extremity when serving and may therefore increase injury risk in tennis players. PMID- 25117873 TI - Cross-education strength and activation after eccentric exercise. AB - CONTEXT: After injury, eccentric exercise of the injured limb is often contraindicated. Cross-education training, whereby the uninvolved limb is exercised, is an alternative that may improve quadriceps muscle strength and activation in the unexercised limb. OBJECTIVE: To determine the effect of eccentric exercise on quadriceps strength and activation gains in the unexercised limb. PATIENTS OR OTHER PARTICIPANTS: Eighteen healthy individuals were randomly assigned to an eccentric training group or a control group. INTERVENTION(S): Quadriceps strength and activation measures were collected at preintervention, midintervention, and postintervention. Eccentric training participants exercised their dominant limb with a dynamometer in eccentric mode at 60 degrees /s, 3 times per week for 8 weeks. MAIN OUTCOME MEASURE(S): Quadriceps strength was quantified at 30 degrees and 60 degrees /s in concentric and eccentric modes. Quadriceps activation was assessed using the burst superimposition technique and quantified via the central activation ratio. A 2 * 3 repeated-measures analysis of variance was used to detect the effects of group and testing session on quadriceps strength and activation. Where appropriate, post hoc Bonferroni multiple-comparisons procedures were used. RESULTS: We found greater eccentric strength in the unexercised limbs of eccentric training participants between preintervention and midintervention and between preintervention and postintervention (preintervention to midintervention: 30 degrees /s P = .05; preintervention to postintervention: 30 degrees /s P = .02, 60 degrees /s P = .02). No differences were noted in concentric strength (P > .05). An overall trend toward greater quadriceps activation in the unexercised knee was detected between preintervention and postintervention (P = .063), with the eccentric training group demonstrating a strong effect (Cohen d = 0.83). Control strength did not change (P > .05). CONCLUSIONS: Exercising with eccentric actions resulted in mode-specific and velocity-specific gains in quadriceps strength in the unexercised limb. A trend toward greater quadriceps activation in the unexercised knee was noted, suggesting that strength gains may have occurred because of enhanced neural activity. This type of therapy may be a useful addition to rehabilitation programs designed to improve quadriceps strength. PMID- 25117872 TI - What's behind a sand fly bite? The profound effect of sand fly saliva on host hemostasis, inflammation and immunity. AB - Sand flies are blood-feeding insects and vectors of the Leishmania parasite. For many years, saliva of these insects has represented a gold mine for the discovery of molecules with anti-hemostatic and immuno-modulatory activities. Furthermore, proteins in sand fly saliva have been shown to be a potential vaccine against leishmaniasis and also markers of vector exposure. A bottleneck to progress in these areas of research has been the identification of molecules responsible for the observed activities and properties of saliva. Over the past decade, rapid advances in transcriptomics and proteomics resulted in the completion of a number of sialomes (salivary gland transcriptomes) and the expression of several recombinant salivary proteins from different species of sand fly vectors. This review will provide readers with a comprehensive update of recent advances in the characterization of these salivary molecules and their biological activities and offer insights pertaining to their protective effect against leishmaniasis and their potential as markers of vector exposure. PMID- 25117874 TI - Holistic life-span health outcomes among elite intercollegiate student-athletes. AB - CONTEXT: Competitive sports are recognized as having unique health benefits and risks, and the effect of sports on life-span health among elite athletes has received increasing attention. However, supporting scientific data are sparse and do not represent modern athletes. OBJECTIVE: To assess holistic life-span health and health-related quality-of-life (HRQL) among current and former National Collegiate Athletic Association student-athletes (SAs). DESIGN: Cross-sectional study. SETTING: A large Division I university. PATIENTS OR OTHER PARTICIPANTS: Population-based sample of 496 university students and alumni (age 17-84 years), including SAs and an age-matched and sex-matched nonathlete (NA) control group. MAIN OUTCOME MEASURE(S): Participants completed anonymous, self-report questionnaires. We measured the Short-Form 12 (SF-12) physical and mental component HRQL scores and cumulative lifetime experience and relative risk of treatment for joint, cardiopulmonary, and psychosocial health concerns. RESULTS: Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs (larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95% confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary health concerns than younger alumni (summary score P < .001; d = 1.05; pCID = 85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID >99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs. Current SAs demonstrated evidence of better psychosocial health (summary score P = .006; d = -0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50; pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI = 0.39, 1.9). Psychosocial health and mental component HRQL were similar between alumni SAs and NAs. No differences were observed between SAs and NAs in physical component HRQL. CONCLUSIONS: The SAs demonstrated significant, clinically meaningful evidence of greater joint health concerns later in life, comparable cardiopulmonary health, and differences in life-span psychosocial health and HRQL profiles compared with NAs. These data provide timely evidence regarding a compelling public issue and highlight the need for further study of life-span health among modern athletes. PMID- 25117876 TI - Effect of electrohydraulic shockwave treatment on tenderness, muscle cathepsin and peptidase activities and microstructure of beef loin steaks from Holstein young bulls. AB - Hydrodynamic pressure processing (HDP) or shockwave treatment improved tenderness (18% reduction in Warner-Bratzler shear force (WBSF) of beef loin steaks. Endogenous muscle proteolyic activities (cathepsins and peptidases) and protein fragmentation of sarcoplasmic and myofibrillar proteins detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were not influenced by HDP. However, microstructure changes were clearly detected using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Specifically a disruption of the structure at the muscle fiber bundles and an increased endomysium space were observed. The present paper supports the evidence of physical disruption of the muscle fibers as a cause behind the tenderness improvement. The paper discusses the possible mechanisms responsible for the meat tenderisation induced by HDP treatment. PMID- 25117875 TI - Risk of Lower Extremity Injury in a Military Cadet Population After a Supervised Injury-Prevention Program. AB - CONTEXT: Specific movement patterns have been identified as possible risk factors for noncontact lower extremity injuries. The Dynamic Integrated Movement Enhancement (DIME) was developed to modify these movement patterns to decrease injury risk. OBJECTIVE: To determine if the DIME is effective for preventing lower extremity injuries in US Military Academy (USMA) cadets. DESIGN: Cluster randomized controlled trial. SETTING: Cadet Basic Training at USMA. PATIENTS OR OTHER PARTICIPANTS: Participants were 1313 cadets (1070 men, 243 women). INTERVENTION(S): Participants were cluster randomized to 3 groups. The active warm-up (AWU) group performed standard Army warm-up exercises. The DIME groups were assigned to a DIME cadre-supervised (DCS) group or a DIME expert-supervised (DES) group; the former consisted of cadet supervision and the latter combined cadet and health professional supervision. Groups performed exercises 3 times weekly for 6 weeks. MAIN OUTCOME MEASURE(S): Cumulative risk of lower extremity injury was the primary outcome. We gathered data during Cadet Basic Training and for 9 months during the subsequent academic year. Risk ratios and 95% confidence intervals (CIs) were calculated to compare groups. RESULTS: No differences were seen between the AWU and the combined DIME (DCS and DES) groups during Cadet Basic Training or the academic year. During the academic year, lower extremity injury risk in the DES group decreased 41% (relative risk [RR] = 0.59; 95% CI = 0.38, 0.93; P = .02) compared with the DCS group; a nonsignificant 25% (RR = 0.75; 95% CI = 0.49, 1.14; P = .18) decrease occurred in the DES group compared with the AWU group. Finally, there was a nonsignificant 27% (RR = 1.27; 95% CI = 0.90, 1.78; P = .17) increase in injury risk during the academic year in the DCS group compared with the AWU group. CONCLUSIONS: We observed no differences in lower extremity injury risk between the AWU and combined DIME groups. However, the magnitude and direction of the risk ratios in the DES group compared with the AWU group, although not statistically significant, indicate that professional supervision may be a factor in the success of injury-prevention programs. PMID- 25117877 TI - Is health a right for all? An umbrella review of the barriers to health care access faced by migrants. AB - OBJECTIVE: To synthesise the scientific evidence concerning barriers to health care access faced by migrants. We sought to critically analyse this evidence with a view to guiding policies. DESIGN: A systematic review methodology was used to identify systematic and scoping reviews which quantitatively or qualitatively analysed data from primary studies. The main variables analysed were structural and contextual barriers (health system organisation) as well as individual (patients and providers). The quality of evidence from the systematic reviews was critically appraised. From 2674 reviews, 79 were retained for further scrutiny, and finally 9 met the inclusion criteria. RESULTS: The structural barriers identified were the lack of health insurance and the high cost of drugs (non universal health system) and organisational aspects of health system (social insurance system and national health system). The individual barriers were linguistic and cultural. None of the reviews provided a quality appraisal of the studies. CONCLUSIONS: Barriers to health care for migrants range from entitlement in non-universal health systems to accessibility in universal ones, and determinants of access to the respective health services should be analysed within the corresponding national context. Generate social and institutional changes that eliminate barriers to access to health services is essential to ensure health for all. PMID- 25117878 TI - Factors characterizing access and latency to first pharmacological treatment in Italian patients with schizophrenia, mood, and anxiety spectrum disorders. AB - Latency to first pharmacological treatment [duration of untreated illness (DUI)] in psychiatric disorders can be measured in years, with differences across diagnostic areas and relevant consequences in terms of socio-occupational functioning and outcome. Within the psychopathological onset of a specific disorder, many factors influence access and latency to first pharmacotherapy and the present study aimed to investigate such factors, through an ad-hoc developed questionnaire, in a sample of 538 patients with diagnoses of schizophrenia spectrum disorder (SZ), mood disorder (MD), and anxiety disorder (AD). Patients with SZs showed earlier ages at onset, first diagnosis and treatment, as well as shorter DUI compared with other patients (43.17 months vs. 58.64 and 80.43 months in MD and AD; F=3.813, P=0.02). Patients with MD and AD reported more frequently onset-related stressful events, benzodiazepines as first treatment, and autonomous help seeking compared with patients with SZs. In terms of first therapist, psychiatrist referral accounted for 43.6% of the cases, progressively decreasing from SZ to MD and AD (57.6, 41.8, and 38.3%, respectively). The opposite phenomenon was observed for nonpsychiatrist clinician referrals, whereas psychologist referrals remained constant. The present findings confirm the presence of a relevant DUI in a large sample of Italian patients with different psychiatric disorders (5 years, on average), pointing out specific differences, in terms of treatment access and latency, between psychotic and affective patients. Such aspects are relevant for detection of at-risk patients and implement early intervention programs. PMID- 25117881 TI - Exercise and cardiovascular diseases. AB - Exercise is a physiologic stressor that has multiple beneficial effects on cardiovascular system. Currently exercise training is a class I intervention as part of a multifactorial long-term process that includes: clinical assistance, assessment of global cardiovascular risk, identification of specific objective for each cardiovascular risk factor, formulation of an individual treatment plan with multiple intervention aimed at reduction of the risk, educational programs, planning of long term follow-up. This paper reviews the evidences of benefit of exercise in the most common heart diseases and describes the role of exercise training in the cardiac rehabilitation programs. PMID- 25117880 TI - Renal denervation as a friend of catheter ablation in patients with atrial fibrillation and hypertension. PMID- 25117879 TI - An exploratory spatial analysis of geographical inequalities of birth intervals among young women in the Democratic Republic of Congo (DRC): a cross-sectional study. AB - BACKGROUND: The length of time between two successive live births (birth interval), is associated with child survival in the developing world. Short birth intervals (<24 months) contribute to infant and child mortality risks. Contraceptive use contributes to a reduction in short birth intervals, but evidence is lacking in the DRC. We aimed to investigate the proportion of short birth intervals at the provincial level among young women in the DRC. METHODS: Data from the Demographic and Health Survey undertaken in the DRC in 2007 were analyzed. Logistic regression and Bayesian geo-additive models were used to explain provincial inequalities in short birth intervals among women of reproductive age and young women. Posterior odds ratio (OR) and 95% credible region (CR) were estimated via Markov chain Monte Carlo (MCMC) techniques. Posterior spatial effects and the associated posterior probability maps were produced at the provincial-level to highlight provinces with a significant higher risk of short birth interval. RESULTS: The overall proportion of short birth intervals among all women of reproductive age (15-49 years) and young women (15 24 years) were 30.2% and 38.7% respectively. In multivariate Bayesian geo additive regression analyses, among the whole sample of women, living in rural areas [OR = 1.07, 95% CR: (0.97, 1.17)], exclusive breastfeeding [1.08 (1.00, 1.17)] and women with primary education [1.06 (1.00, 1.16)], were consistently associated with a higher risk of short birth intervals. For the young women, none of the factors considered were associated with the risk of short birth interval except a marginal effect from the lack of education. There was a spatial variation in the proportion of women reporting short birth intervals and among all women of reproductive age across provinces, with Nord-Kivu [1.12 (1.02, 1.24)], Sud Kivu [1.17 (1.05, 1.29)] and Kasai Occidental [1.18 (1.06, 1.32)] reporting a higher risk of short birth intervals. For young women, the higher risk provinces were Nord-Kivu [1.22 (1.00, 1.54)] and Sud Kivu [1.34 (1.14, 1.63)]. CONCLUSIONS: This study suggests distinct geographic patterns in the proportion of short birth intervals among Congolese women, as well as the potential role of demographic and geographic location factors driving the ongoing higher youth fertility, higher childhood and maternal mortality in the DRC. PMID- 25117882 TI - Changes in serum asymmetric dimethylarginine and endothelial markers levels with varying periods of hemodialysis. AB - Asymmetric dimethylarginine (ADMA) as a uremia toxin is accumulated in end-stage renal disease (ESRD) patients. Elevated ADMA level has been shown to be predictive of cardiovascular diseases (CVDs) and all-cause mortality in ESRD. Therefore, we investigated the effect of prolonged hemodialysis (HD) treatment on the levels of serum ADMA, arginine, nitric oxide (NO), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). Seventy-five patients (M/F = 40/35) with chronic renal failure (CRF) and who were on HD were divided into five groups with differing treatment periods of HD; from 6 to 24 months to 97-120 months. Fifteen apparently healthy subjects acted as controls. The serum levels of ADMA, sICAM-1 and sVCAM-1 were increased in all patient groups compared to the control group. No significant difference was observed when the patient groups were compared in terms of HD treatment periods. Nitric oxide levels were lower in the three groups who were treated for periods of 49-72, 73-96, 97-120 months compared to the control group. The L arginine to ADMA ratio was decreased in all patient groups compared to controls. Consequently, our investigations have shown that in HD continued for more than 4 years NO levels began to decrease significantly and the levels of serum ADMA, sICAM-1 and sVCAM-1 levels increased although this increase was not affected by the period in which hemodialysis treatment was applied. PMID- 25117883 TI - New bone formation induced by minimodeling in a hemodialysis patient treated with cinacalcet. PMID- 25117887 TI - Determinants of modern family planning use among women of reproductive age in the Nkwanta district of Ghana: a case-control study. AB - BACKGROUND: Average contraceptive prevalence rate in the Nkwanta district of Ghana was estimated to be 6.2% relative to the national average at the time, of 19%. While several efforts had been made to improve family planning in the country, the district still had very low use of modern family planning methods. This study sought to determine the factors that influenced modern family planning use in general and specifically, the factors that determined the consistently low use of modern family planning methods in the district. METHODS: A case-control study was conducted in the Nkwanta district of Ghana to determine socio-economic, socio-cultural and service delivery factors influencing family planning usage. One hundred and thirty cases and 260 controls made up of women aged 15-49 years were interviewed using structured questionnaires. A logistic regression was fitted. RESULTS: Awareness and knowledge of modern family planning methods were high among cases and controls (over 90%). Lack of formal education among women, socio-cultural beliefs and spousal communication were found to influence modern family planning use. Furthermore, favourable opening hours of the facilities and distance to health facilities influenced the use of modern contraceptives. CONCLUSION: While modern family planning seemed to be common knowledge among these women, actual use of such contraceptives was limited. There is need to improve use of modern family planning methods in the district. In addition to providing health facilities and consolidating close-to-client service initiatives in the district, policies directed towards improving modern family planning method use need to consider the influence of formal education. Promoting basic education, especially among females, will be a crucial step as the district is faced with high levels of school dropout and illiteracy rates. PMID- 25117886 TI - Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction. AB - Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites 3,4-dihydroxyphenyacetic acid (DOPAC), homovanillic acid (HVA), and 5 hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 min after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or post traumatic stress disorder. PMID- 25117889 TI - School-level factors associated with increased fruit and vegetable consumption among students in California middle and high schools. AB - BACKGROUND: This study assessed associations between selective school-level factors and students' consumption of fruits and vegetables at school. Better understanding of school factors associated with increased produce consumption is especially important, as students are served more produce items at school. METHODS: This cross-sectional study included 5439 seventh- and ninth-grade students from 31 schools in California in 2010. Multilevel regression models estimated whether the odds of consuming fruits or vegetables at school among students eating the school lunch were associated with the length of the lunch period, quality/variety of produce options, or other factors. RESULTS: A longer lunch period was associated with increased odds of a student eating fruits (odds ratio [OR] = 1.40) and vegetables (OR = 1.54) at school. Better fruit quality increased the odds of a student consuming fruit (OR = 1.44). Including a salad bar and involving students in food service decisions increased a student's odds of consuming vegetables (OR = 1.48 and OR = 1.34, respectively). CONCLUSIONS: This study suggests that institutional factors in schools are positively associated with middle and high school students' consumption of produce items at school. Additional efforts to structure school meal environments to enhance students' consumption of produce items can benefit students' nutrition and health. PMID- 25117888 TI - Relationship between frequency and intensity of cigarette smoking and TTFC/C among students of the GYTS in select countries, 2007-2009. AB - BACKGROUND: This study assessed the construct validity of a measure of nicotine dependence that was used in the Global Youth Tobacco Survey (GYTS). METHODS: Using 2007-2009 data from the GYTS, subjects from 6 countries were used to assess current smokers' odds of reporting time to first cigarette or craving positive (TTFC/C+) by the number of cigarette smoking days per month (DPM) and the number of cigarettes smoked per day (CPD). RESULTS: The percentage of GYTS smokers who reported TTFC/C+ ranged from 58.0% to 69.7%. Compared with students who smoked on 1-2 DPM, those who smoked on 3-9 DPM had 3 times the adjusted odds of reporting TTFC/C+. The adjusted odds of reporting TTFC/C+ were 3 to 7 times higher among those who smoked 10-29 DPM and 6 to 20 times higher among daily smokers. Similarly, the adjusted odds of TTFC/C+ were 3-6 times higher among those who smoked 2-5 CPD and 6 to 20 times higher among those who smoked >6 CPD, compared to those who smoked <1 CPD. CONCLUSION: Associations of TTFC/C+ prevalence with both frequency and intensity of cigarette smoking provide a construct validation of the GYTS question used to assess respondents' TTFC/C status. PMID- 25117890 TI - Classroom carbon dioxide concentration, school attendance, and educational attainment. AB - BACKGROUND: We tested the hypothesis that classroom carbon dioxide (CO2 ) concentration is inversely related to child school attendance and educational attainment. METHODS: Concentrations of CO2 were measured over a 3-5 day period in 60 naturally ventilated classrooms of primary school children in Scotland. Concentrations of CO2 were related to the class average annual attendance and proportions attaining a national standard for reading, writing, and numeracy, adjusted for socioeconomic status and class size. RESULTS: The median (interquartile range, IQR) CO2 concentration averaged over the school day was 1086 ppm (922, 1310). In the model, Time Weighted Average CO2 concentrations were inversely associated with school attendance but not academic attainments. An increase of 100 ppm CO2 was associated with a reduced annual attendance of 0.2% (0.04, 0.4) roughly equivalent to 1 half day of school per annum, assuming schools are open on 190 days per year. Indoor temperature and relative humidity were not related to attendance or academic attainment. CONCLUSIONS: Inadequate classroom ventilation, as evidenced by CO2 concentration exceeding 1000 ppm, is not uncommon and may be associated with reduced school attendance. A relationship between inadequate classroom ventilation and adverse health outcomes in children may be present and this needs to be explored. PMID- 25117891 TI - School bus crash rates on routine and nonroutine routes. AB - BACKGROUND: Although prior research has established that school buses are a safe form of transportation, crashes can produce catastrophic consequences. School buses have 2 types of routes: predictable, routine routes that take children to and from school and less predictable, nonroutine routes for school events. No studies have examined school bus crash incidence and characteristics by these route types. METHODS: School bus crashes were identified from the Iowa Department of Transportation Crash Database from mid-2005 through mid-2010. Crash reports did not identify whether the bus was on a routine or nonroutine route, so a protocol to assign these based on day and time was developed. Bus mileage was provided by the Iowa Department of Education. RESULTS: The school bus crash rate was 2.1 times higher on nonroutine routes than on routine routes (95% CI = 1.8 2.3). Most crashes involved an improper action by the driver of another vehicle. In crashes attributed to improper actions of school buses, failure to yield the right-of-way and disregarding traffic signs were more common on routine routes, while losing control, speeding, reckless, or aggressive driving were more common on nonroutine routes. CONCLUSIONS: School bus crashes are more likely to occur on nonroutine routes. PMID- 25117892 TI - The "ins" and "outs" of physical activity policy implementation: inadequate capacity, inappropriate outcome measures, and insufficient funds. AB - BACKGROUND: Despite broad public support and legislative activity, policies intended to promote physical activity in schools have not produced positive outcomes in levels of physical activity or student health. What explains the broad failure of Physical Activity Policies (PAPs)? Thus far, PAP research has used limited quantitative methods to assess PAP outcomes. New paradigms of qualitative policy implementation research can make important contributions to explaining the causes of policy failure and to the future design of more efficacious PAP legislation. METHODS: This analysis is a case study of South Carolina's 2005 Student Health and Fitness Act (SHFA). Written documents, investigators' observation and experience, and an interview with a key stakeholder were analyzed to for themes based on theoretical frameworks from education implementation research including (1) bottom-up and top-down perspectives, (2) conceptualizing policy as practice, and (3) the implementer as learner. RESULTS: "Weak policy signals" in SHFA undermined the implementation of PAP in 3 problematic areas: inadequate capacity development for implementers, inappropriate measures of implementation, and insufficient funding. CONCLUSIONS: These findings illustrate the contributions of qualitative research and establish the need for further qualitative research into PAP implementation processes. To ensure successful future physical activity policies, policymakers, and stakeholders need to consider implementation, evaluation, and funding from the beginning phases of policy development. PMID- 25117893 TI - Influenza vaccination coverage among school employees: assessing knowledge, attitudes, and behaviors. AB - BACKGROUND: Influenza can spread among students, teachers, and staff in school settings. Vaccination is the most effective method to prevent influenza. We determined 2012-2013 influenza vaccination coverage among school employees, assessed knowledge and attitudes regarding the vaccine, and determined factors associated with vaccine receipt. METHODS: We surveyed 412 (49%) of 841 employees at 1 suburban Ohio school district in March 2013. The Web-based survey assessed personal and work characteristics, vaccine receipt, and knowledge and attitudes regarding the vaccine. RESULTS: Overall, 238 (58%) respondents reported getting the 2012-2013 influenza vaccine. The most common reason for getting the vaccine was to protect oneself or one's family (87%). Beliefs that the vaccine was not needed (32%) or that it was not effective (21%) were the most common reasons for not getting it. Factors independently associated with vaccine receipt were having positive attitudes toward the vaccine, feeling external pressure to get it, and feeling personal control over whether to get it. CONCLUSIONS: Influenza vaccine coverage among school employees should be improved. Messages encouraging school employees to get the vaccine should address misconceptions about the vaccine. Employers should use methods to maximize employee vaccination as part of a comprehensive influenza prevention program. PMID- 25117894 TI - Measuring school climate in high schools: a focus on safety, engagement, and the environment. AB - BACKGROUND: School climate has been linked to multiple student behavioral, academic, health, and social-emotional outcomes. The US Department of Education (USDOE) developed a 3-factor model of school climate comprised of safety, engagement, and environment. This article examines the factor structure and measurement invariance of the USDOE model. METHODS: Drawing upon 2 consecutive waves of data from over 25,000 high school students (46% minority), a series of exploratory and confirmatory factor analyses examined the fit of the Maryland Safe and Supportive Schools Climate Survey with the USDOE model. RESULTS: The results indicated adequate model fit with the theorized 3-factor model of school climate, which included 13 subdomains: safety (perceived safety, bullying and aggression, and drug use); engagement (connection to teachers, student connectedness, academic engagement, school connectedness, equity, and parent engagement); environment (rules and consequences, physical comfort, and support, disorder). We also found consistent measurement invariance with regard to student sex, grade level, and ethnicity. School-level interclass correlation coefficients ranged from 0.04 to .10 for the scales. CONCLUSIONS: Findings supported the USDOE 3-factor model of school climate and suggest measurement invariance and high internal consistency of the 3 scales and 13 subdomains. These results suggest the 56-item measure may be a potentially efficient, yet comprehensive measure of school climate. PMID- 25117895 TI - Employment status among parenting teenage mothers enrolled in high school. AB - BACKGROUND: Many programs emphasize subsequent pregnancy prevention and high school graduation among teenage mothers; however, less is known about their ability to increase financial earnings from employment opportunities while concurrently enrolled in school. This study evaluates factors influencing employment status among teenage mothers after enrolling in a community-based randomized intervention. METHODS: Project Mothers and Schools (PMAS) initiative participants were surveyed at baseline and 12 months after enrollment. The 56 control group participants received homebound education and family case management, whereas the 59 intervention group participants received these basic level services as well as group parenting time, life skills, and leadership training. A generalized estimating equation was used to identify statistically significant changes associated with the intervention. RESULTS: Participants were significantly more likely to receive money from their jobs at postintervention relative to baseline (OR = 4.75, p = .023); however, this change was not statistically significant when comparing the control group to the intervention group. At postintervention, those who received money from parents were significantly less likely to receive money from their job (OR = 0.12, p = .002). CONCLUSIONS: While PMAS benefited participants in terms of employment, the role of parental support requires additional investigation to determine its influence on teenage mothers' ability to achieve financial independence. PMID- 25117896 TI - State-level school competitive food and beverage laws are associated with children's weight status. AB - BACKGROUND: This study attempted to determine whether state laws regulating low nutrient, high energy-dense foods and beverages sold outside of the reimbursable school meals program (referred to as "competitive foods") are associated with children's weight status. METHODS: We use the Classification of Laws Associated with School Students (CLASS) database of state codified law(s) relevant to school nutrition. States were classified as having strong, weak, or no competitive food laws in 2005 based on strength and comprehensiveness. Parent-reported height and weight along with demographic, behavioral, family, and household characteristics were obtained from the 2007 National Survey of Children's Health. Bivariate and logistic regression analyses estimated the association between states' competitive food laws and children's overweight and obesity status (body mass index [BMI]-for-age >=85th percentile). Children (N = 16,271) between the ages of 11-14 years with a BMI for age >=5th percentile who attended public school were included. RESULTS: Children living in states with weak competitive food laws for middle schools had over a 20% higher odds of being overweight or obese than children living in states with either no or strong school competitive food laws. CONCLUSION: State-level school competitive food and beverage laws merit attention with efforts to address the childhood obesity epidemic. Attention to the specificity and requirements of these laws should also be considered. PMID- 25117897 TI - Characterization of Coffee ringspot virus-Lavras: a model for an emerging threat to coffee production and quality. AB - The emergence of viruses in Coffee (Coffea arabica and Coffea canephora), the most widely traded agricultural commodity in the world, is of critical concern. The RNA1 (6552nt) of Coffee ringspot virus is organized into five open reading frames (ORFs) capable of encoding the viral nucleocapsid (ORF1p), phosphoprotein (ORF2p), putative cell-to-cell movement protein (ORF3p), matrix protein (ORF4p) and glycoprotein (ORF5p). Each ORF is separated by a conserved intergenic junction. RNA2 (5945nt), which completes the bipartite genome, encodes a single protein (ORF6p) with homology to RNA-dependent RNA polymerases. Phylogenetic analysis of L protein sequences firmly establishes CoRSV as a member of the recently proposed Dichorhavirus genus. Predictive algorithms, in planta protein expression, and a yeast-based nuclear import assay were used to determine the nucleophillic character of five CoRSV proteins. Finally, the temperature dependent ability of CoRSV to establish systemic infections in an initially local lesion host was quantified. PMID- 25117898 TI - Circulating levels of chemokines in psoriasis. AB - Chemokines may contribute to local and systemic inflammation in patients with psoriasis. Previous studies have demonstrated the importance of chemokine ligands and receptors in the recruitment of T cells into psoriatic lesional skin and synovial fluid. The aim of this study was to evaluate the levels of Th1-related chemokines in psoriasis and to investigate any association with disease severity. We quantified serum levels of CXCL9, CXCL10 and CXCL16 and the frequencies of CD4+CXCR3+ T lymphocytes through ELISA and flow cytometry, respectively. A total of 38 patients with psoriasis and 33 controls were included. There were no significant differences in chemokine levels between psoriasis and control groups. Patients with psoriatic arthritis had lower median level of CXCL10 when compared with controls (p=0.03). There were no significant correlations between serum chemokines analyzed and disease severity. Frequencies of CD4+CXCR3+ T cells were lower in patients with psoriasis than in controls (p<0.01). A sensitivity analysis excluding patients on systemic therapy yielded similar results. Serum concentrations of CXCL9, CXCL10 and CXCL16 were not increased in the psoriasis group or correlated with disease severity. Systemic levels of chemokine ligands do not seem to be sensitive biomarkers of disease activity or accurate parameters to predict response to therapy. Frequencies of CD4+CXCR3+ T cells were decreased in the peripheral blood of psoriasis patients, possibly due to recruitment to inflammatory lesions. PMID- 25117899 TI - NMR characterization of the electrostatic interaction of the basic residues in HDGF and FGF2 during heparin binding. AB - Electrostatic interaction is a major driving force in the binding of proteins to highly acidic glycosaminoglycan, such as heparin. Although NMR backbone chemical shifts have generally been used to identify the heparin-binding site on a protein, however, there is no correlation between the binding free energies and the perturbed backbone chemical shifts for individual residues. The binding event occurs at the end of a side chain of basic residue, and does not require causing significant alterations in the backbone environment at a distance of multiple bonds. We used the H2CN NMR pulse sequence to detect heparin binding through the side-chain resonances Hepsilon-Cepsilon-Nzeta of Lys and Hdelta-Cdelta-Nepsilon of Arg in the two proteins of hepatoma-derived growth factor (HDGF) and basic fibroblast growth factor (FGF2). H2CN titration experiments revealed chemical shift perturbations in the side chains, which were correlated with the free energy changes in various mutants. The residues K19 in HDGF and K125 in FGF2 demonstrated the most significant perturbations, consistent with our previous observation that the two residues are crucial for binding. The result suggests that H2CN NMR provides a precise evaluation for the electrostatic interactions. The discrepancy observed between backbone and side chain chemical shifts is correlated to the solvent accessibility of residues that the K19 and K125 backbones are highly buried with the restricted backbone conformation and are not strongly affected by the events at the end of the side chains. PMID- 25117905 TI - Bevacizumab revisited: its use in different mouse models of ocular pathologies. AB - PURPOSE: Previous reports have yielded conflicting data on the activity of bevacizumab (Avastin), a recombinant humanized monoclonal antibody against VEGF A, in the mouse. The current study was designed to further explore the use of this VEGF inhibitor in various murine models of ocular diseases and compare it to the widely used murine anti-VEGF-R2 neutralizing antibody (DC101). METHODS: Murine models of laser-induced choroidal neovascularization (CNV), oxygen-induced retinopathy (OIR) and glaucoma filtration surgery (GFS) were used to investigate the effect of bevacizumab. Mice either received an intravitreal (CNV-OIR) or subconjunctival (GFS) injection. In all models, they were divided in two groups (n = 10 per group). In the first group, one eye was injected with bevacizumab (1 ul; 25 ug) and the other eye was used as a negative control and received an injection of NaCl (1 ul; 0.9%). In the second group, one eye was injected with DC101 (1 ul; 6.2 ug), whereas an isotype-matched control antibody (1C8; 4.8 ug) was administered in the contralateral eye. Treatment outcome was studied by clinical investigation (GFS) and immunohistological analysis of angiogenesis (CD31/FITC-dextran/H&E) and fibrosis (Sirius Red). RESULTS: Analysis of blood vessel density (CNV) and blood vessel growth (OIR) showed a comparable decrease after intravitreal administration of bevacizumab or DC101. Furthermore, in the mouse model of GFS, clinical investigation of the bleb and a CD31 staining on sections demonstrated that subconjunctival injection of both antibodies similarly improved the surgical outcome (bleb area and survival) by reducing angiogenesis. Moreover, morphometric analysis after Sirius Red staining showed a comparable reduction in collagen deposition after administration of the inhibitors. CONCLUSION: Our findings consistently demonstrate that bevacizumab is as effective as the murine anti-VEGF-R2 antibody (DC101) in mouse models of CNV, OIR and GFS, thus confirming its suitability for translational ophthalmological research. PMID- 25117906 TI - Erlotinib and gastric acid-reducing agents: a combination to avoid or to support? PMID- 25117907 TI - Bayes factor for investigative assessment of selected handwriting features. AB - This paper extends previous research on the use of multivariate continuous data in comparative handwriting examinations, notably for gender classification. A database has been constructed by analyzing the contour shape of loop characters of type a and d by means of Fourier analysis, which allows characters to be described in a global way by a set of variables (e.g., Fourier descriptors). Sample handwritings were collected from right- and left-handed female and male writers. The results reported in this paper provide further arguments in support of the view that investigative settings in forensic science represent an area of application for which the Bayesian approach offers a logical framework. In particular, the Bayes factor is computed for settings that focus on inference of gender and handedness of the author of an incriminated handwritten text. An emphasis is placed on comparing the efficiency for investigative purposes of characters a and d. PMID- 25117908 TI - Quantitative evaluation of the performance of a new test bolus-based computed tomographic angiography contrast-enhancement-prediction algorithm. AB - OBJECTIVES: The objective of this study was to assess the robustness of a novel test bolus (TB)-based computed tomographic angiography (CTA) contrast-enhancement prediction (CEP) algorithm by retrospectively quantifying the systematic and random errors between the predicted and true enhancements. MATERIALS AND METHODS: All local institutional review boards approved this retrospective study, in which a total of 72 (3 * 24) anonymized cardiac CTA examinations were collected from 3 hospitals. All patients (46 men; median age, 62 years [range, 31-81 years]) underwent a TB scan and a cardiac CTA according to local scan and injection protocols. For each patient, a shorter TB signal and TB signals with lower temporal resolution were derived from the original TB signal. The CEP algorithm predicted the enhancement in the descending aorta (DAo) on the basis of the TB signals in the DAo, the injection protocols and kilovolt settings, as well as population-averaged blood circulation characteristics. The true enhancement was extracted with a region of interest along the DAo centerline. For each patient, the errors in timing and amplitude were calculated; differences between the hospitals were assessed using the 1-way analysis of variance (P < 0.05) and variations between the TB signals were assessed using the within-subject standard deviation. RESULTS: No significant differences were found between the 3 hospitals for any of the TB signals. With errors in the amplitude and timing of 0.3% +/- 15.6% and -0.2 +/- 2.0 seconds, respectively, no clinically relevant systematic errors existed. Shorter- and coarser-time-sampled TB signals introduced a within subject standard deviation of 4.0% and 0.5 seconds, respectively. CONCLUSIONS: This TB-based CEP algorithm has no systematic errors in the timing and amplitude of predicted enhancements and is robust against coarser-time-sampled and incomplete TB scans. PMID- 25117909 TI - Physical activity in chronic kidney disease: a plausible approach to vascular calcification? AB - Vascular calcification (VC) is a prominent feature that affects up to 40 to 80% of Chronic Kidney Disease (CKD) patients depending on the degree of renal impairment. Though etiology and pathogenesis of the different types of VC are far from being elucidated, it is conceivable that an imbalance between promoters and inhibitors represents the condition that triggers VC deposition and progression. In addition to traditional cardiovascular risk factors, several lines of evidence suggest that specific factors may affect the arterial system and prognosis in CKD. Over the last decade, a few pharmacological strategies aimed at controlling different selected risk factors for VC have been investigated yielding conflicting results. In light of the complicated interplay between inhibitors and promoters as well as the fact that VC represents the result of cumulative and prolonged exposure to multiple risk factors, a more comprehensive risk modification approach such as lifestyle modification or physical activity (PA) may represent a valid strategy to attenuate VC deposition and progression.We herein aim at reviewing the rationale and current evidence on the potential for lifestyle modification with a specific focus on PA as a cost-effective strategy for VC treatment. PMID- 25117911 TI - Part I: frequency of depression after stroke: an updated systematic review and meta-analysis of observational studies. AB - BACKGROUND: Approximately 15 million people who suffer a stroke globally each year are at risk of developing depression. AIM: To update our systematic review and meta-analysis of the frequency of depression after stroke published in 2005, including studies published before July 2004. METHODS: We included all published observational studies (to 31 May 2013) with prospective consecutive recruitment and quantification of the proportion of people with depression after stroke. We included studies of adult (>18 years) patients with a clinical diagnosis of stroke, where an assessment of depression or depressive symptom burden was performed at a pre-specified time-point for all study participants. RESULTS: Data were available from 61 studies including 25,488 people. The proportional frequency of depression varied considerably across studies; however, the pooled frequency estimate of 31% (95% confidence interval 28% to 35%) was not significantly different from the 33% (difference of 2%, 95% confidence interval <1% to 3%) reported in the 2005 review. The proportion with depression between one and five-years (25%; 95% confidence interval 16 to 33%) and at five years after stroke (23%; 95% confidence interval 14 to 31%) was significantly lower. CONCLUSION: Despite systematic review evidence describing validated depression screening tools and effective treatment and prevention strategies for depression after stroke, there has not been a significant reduction in the proportion of people experiencing depression after stroke. There is a pressing need for increased clinical uptake of evidenced-based strategies to screen for, prevent, and treat depression after stroke. PMID- 25117910 TI - Anti-peroxynitrite treatment ameliorated vasorelaxation of resistance arteries in aging rats: involvement with NO-sGC-cGKs pathway. AB - Declined vasorelaxation function in aging resistance arteries is responsible for aging-related multiple organ dysfunctions. The aim of the present study is to explore the role of peroxynitrite (ONOO-) in aging resistance arterial vasorelaxation dysfunction and the possible mechanism. In the present study, young (3-4 months olds) and aging (20 months olds) male SD rats were randomized to receive vehicle (Saline) or FeTMPyP (ONOO- scavenger) for 2 weeks. The vasorelaxation of resistance arteries was determined in vitro; NOx level was tested by a colorimetric assay; the expression of nitrotyrosine (NT), soluble Guanylate Cyclase (sGC), vasodilator-stimulated phosphoprotein (VASP), phosphorylated VASP (P-VASP) and cGMP in resistance arteries were detected by immunohistochemical staining. In the present study, endothelium-dependent dilation in aging resistance arteries was lower than in those from young rats (young vs. aging: 68.0% +/- 4.5% vs. 50.4% +/- 2.9%, P<0.01). And the endothelium independent dilation remained constant. Compared with young rats, aging increased nitrative stress in resistance arteries, evidenced by elevated NOx production in serum (5.3 +/- 1.0 nmol/ml vs. 3.3 +/- 1.4 nmol/ml, P<0.05) and increased NT expression (P<0.05). ONOO- was responsible for the vasorelaxation dysfunction, evidenced by normalized vasorelaxation after inhibit ONOO- or its sources (P<0.05) and suppressed NT expression after FeTMPyP treatment (P<0.05). The expression of sGC was not significantly different between young and aging resistance arteries, but the cGMP level and P-VASP/VASP ratio (biochemical marker of NO-sGC-cGKs signaling) decreased, which was reversed by FeTMPyP treatment in vivo (P<0.05). The present study suggested that ONOO- mediated the decline of endothelium-dependent vasorelaxation of aging resistance arteries by induction of the NO-sGC-cGKs pathway dysfunction. PMID- 25117913 TI - Oral administration of the AYA strain of Lactobacillus plantarum modulates expression of immunity-related genes in the murine Peyer's patch: a DNA microarray analysis. AB - We performed comprehensive transcriptome analysis of Peyer's patches to elucidate the effects of oral administration of Lactobacillus plantarum strain AYA in mice. Using microarray analysis, we identified 124 upregulated and 144 downregulated genes for four weeks after the start of dietary supplementation with AYA. Gene Ontology analysis revealed that the genes for immune function were enriched in the upregulated gene set. PMID- 25117912 TI - Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis. AB - BACKGROUND: Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice. METHODS: We performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG). RESULTS: Rituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients >= 80 years old. We found that post market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age. CONCLUSIONS: Our results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug. PMID- 25117915 TI - Phenotypic and genetic evidence for ecological speciation of Aquilegia japonica and A. oxysepala. AB - Natural selection is thought to be a driving force that can cause the evolution of reproductive isolation. The genus Aquilegia is a model system to address how natural selection promotes the process of speciation. Morphological differences between A. oxysepala, A. japonica and their hybrids were quantified for two vegetative (plant height and leaf area) and three floral morphological (sepal area, corolla length and diameter) traits. We also evaluated the genetic variability of the two species and their hybrids based on two chloroplast (1225 bp), four nuclear (5811 bp) genes and 15 microsatellites. Our results revealed that differentiation of A. japonica and A. oxysepala at the ecological and morphological levels also involved divergence at the genetic level. In addition, the analysis of nucleotide variation patterns showed that the two species possessed numerous fixation sites at nuclear genes gAA4, gA7 and gAA12. Furthermore, we found that all of the phenotypic hybrids also showed a genetically admixed ancestry. These findings suggest that natural selection has indeed facilitated the formation of distinct genetic variation patterns in the two Aquilegia species and habitat adaptation has been driving the ecologically based evolution of reproductive isolation. PMID- 25117916 TI - Kaiser Permanente's commitment to breastfeeding. PMID- 25117914 TI - Shotgun approaches to gait analysis: insights & limitations. AB - BACKGROUND: Identifying features for gait classification is a formidable problem. The number of candidate measures is legion. This calls for proper, objective criteria when ranking their relevance. METHODS: Following a shotgun approach we determined a plenitude of kinematic and physiological gait measures and ranked their relevance using conventional analysis of variance (ANOVA) supplemented by logistic and partial least squares (PLS) regressions. We illustrated this approach using data from two studies involving stroke patients, amputees, and healthy controls. RESULTS: Only a handful of measures turned out significant in the ANOVAs. The logistic regressions, by contrast, revealed various measures that clearly discriminated between experimental groups and conditions. The PLS regression also identified several discriminating measures, but they did not always agree with those of the logistic regression. DISCUSSION & CONCLUSION: Extracting a measure's classification capacity cannot solely rely on its statistical validity but typically requires proper post-hoc analysis. However, choosing the latter inevitably introduces some arbitrariness, which may affect outcome in general. We hence advocate the use of generic expert systems, possibly based on machine-learning. PMID- 25117917 TI - Mental health trajectories and their embeddedness in work and family circumstances: a latent state-trait approach to life-course trajectories. AB - Mental health trajectories are known to be influenced by work and family circumstances. However, few studies have examined both of these influences simultaneously in a longitudinal manner. The life-course perspective stresses the importance of examining trajectories in terms of both stable and dynamic components. In this article we use structural equation models (latent state trait, LST) to distinguish the stable and situational components of mental health trajectories and hypothesise that situational mental health is influenced by satisfaction with work and family, and this effect differs by gender. An analysis of data from a nationally representative sample of 1616 working Swiss residents (2000-2006) shows that mental health trajectories are mostly stable and only slightly sensitive to situational influences. However, situational influences in a given wave do predict situational influences in the next wave. Satisfaction with work and family influences situational mental health in both genders, but the impact is greater for men. In conclusion, the LST approach allows for the examination of mental health trajectories from a life-course perspective by distinguishing stable and situational components. Mental health trajectories are more stable and constant than they are dependent on work and family circumstances, and men are more sensitive to family circumstances than women. PMID- 25117918 TI - The placebo effect in early-phase glaucoma clinical trials. AB - PURPOSE: To analyze the extent and prevalence of the placebo effect in prior early-phase glaucoma clinical studies. METHODS: Articles were evaluated on phase I and II trials of glaucoma medicines that became commercially available after 1977 with a placebo arm that involved glaucoma patients. RESULTS: We included 23 studies with 23 treatment arms with a total of 1703 patients in articles evaluating 10 different glaucoma medications. This study showed that at 8 AM (n = 18), the average decrease in placebo from untreated baseline was 2.3 +/- 1.6 mm Hg (9%), while for the diurnal curve (n = 17), the mean decrease was 1.4 +/- 1.1 mm Hg (6%). At 8 AM, 8/18 treatment arms had greater than 2 mm Hg intraocular pressure (IOP) decrease, and all had at least some reduction in IOP. For the diurnal curve, 4 of 17 studies had reduced IOP greater than 2 mm Hg. One treatment arm had no placebo effect. CONCLUSIONS: This study suggests that a placebo effect is common in glaucoma clinical trials and potentially could limit the ability to evaluate the efficacy of a new medicine. PMID- 25117919 TI - Frailty, disability and physical exercise in the aging process and in chronic kidney disease. AB - Frailty in the elderly is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. It is usually associated to adverse health outcomes and to one-year mortality risk. Physical exercise has found to be effective in preventing frailty and disability in this population. Chronic kidney disease (CKD) is also a clinical condition where protein energy-wasting, sarcopenia and dynapenia ,very common symptoms in the frail elderly, may occur. Moreover elderly and CKD patients are both affected by an impaired physical performance that may be reversed by physical exercise with an improvement of the survival rate. These similarities suggest that frailty may be a common pathway of aging and CKD that may induce disability and that can be prevented by a multidimensional approach in which physical exercise plays an important role. PMID- 25117928 TI - Impact of 5-aminolevulinic acid fluorescence-guided surgery on the extent of resection of meningiomas--with special regard to high-grade tumors. AB - BACKGROUND AND OBJECTIVES: In high-grade meningiomas and a subgroup of clinically aggressive benign meningiomas tumor control is still insufficient. Recently 5-ALA fluorescence in meningiomas was reported. The impact of 5-ALA fluorescence-guided surgery (FGS) on surgical decision-making and extent of resection has not yet been systematically analyzed, especially not in high-grade meningiomas. The present study deals with three main questions regarding 5-ALA FGS in meningiomas: to assess the potential for discriminating different WHO grades intra operatively, to analyze the influence on surgical strategy and to evaluate the impact on extent of resection. METHODS: Data from 31 meningiomas operated with 5 ALA FGS were retrospectively analyzed. Intraoperative fluorescence was graded by the surgeon as "no", "low" or "high". Correlations between semi-quantitative fluorescence and histological features (WHO grade) were analyzed. The influence of 5-ALA fluorescence on surgical strategy and the impact of 5-ALA FGS on degree of resection (Simpson grade and post-operative imaging) were studied. In tumors showing infiltrative growth the extent of resection of fluorescence positive tissue was evaluated. RESULTS: The population comprised 19 WHO grade I, 8 grade II and 4 grade III tumors (61% benign and 39% high-grade meningiomas). 94% of the tumors showed positive fluorescence. Different fluorescence intensities were observed: "no" in two, "high" in 12 and "low" in 17 tumors, respectively. A significant correlation between fluorescence intensity and WHO grade was found (rho=0.557, p=0.001). 5-ALA improved the extent of resection in 3/16 (19%) of grade I and in 6/8 (75%) of grade II/III meningiomas. This improvement was not measurable by the Simpson grading as rated by the surgeon and controlled on post operative imaging. CONCLUSIONS: In the present population a strong correlation between fluorescence intensity and WHO grade was observed. 5-ALA FGS improved the extent of resection in meningiomas. Especially in high-grade tumors additional information on brain and neurovascular infiltration was provided. The improved resection was not measurable by Simpson's grading necessitating an additional item, which rates residual fluorescence. Long-term studies are necessary to evaluate a possible impact of FGS on recurrence and overall survival. PMID- 25117920 TI - Can trained volunteers make a difference at mealtimes for older people in hospital? A qualitative study of the views and experience of nurses, patients, relatives and volunteers in the Southampton Mealtime Assistance Study. AB - BACKGROUND: Malnutrition is common amongst hospitalised older patients and associated with increased morbidity and mortality. Poor dietary intake results from factors including acute illness and cognitive impairment but additionally patients may have difficulty managing at mealtimes. Use of volunteers to help at mealtimes is rarely evaluated. OBJECTIVES: To obtain multiple perspectives on nutritional care of older inpatients, acceptability of trained volunteers and identify important elements of their assistance. DESIGN: A qualitative study 1 year before and after introduction of volunteer mealtime assistants on one ward and parallel comparison with a control ward in a Medicine for Older People department at a UK university hospital. PARTICIPANTS AND METHODS: Semi-structured interviews and focus groups, in baseline and intervention years, with purposively sampled nursing staff at different levels of seniority; patients or close relatives; and volunteers. RESULTS: At baseline staff felt under pressure with insufficient people assisting at mealtimes. Introducing trained volunteers was perceived by staff and patients to improve quality of mealtime care by preparing patients for mealtimes, assisting patients who needed help, and releasing nursing time to assist dysphagic or drowsy patients. There was synergy with other initiatives, notably protected mealtimes. Interviews highlighted the perceived contribution of chronic poor appetite and changes in eating patterns to risk of malnutrition. CONCLUSIONS: Improved quality of mealtime care attributed to volunteers' input has potential to enhance staff morale and patients'/relatives' confidence. A volunteer mealtime assistance scheme may work best when introduced in context of other changes reflecting commitment to improving nutrition. IMPLICATIONS FOR PRACTICE: (i) A mealtime assistance scheme should incorporate training, supervision and support for volunteers; (ii) Good relationships and a sense of teamwork can develop between wards staff and volunteers; (iii) Impact may be maximised in the context of 'protected mealtimes'. PMID- 25117930 TI - Ethical considerations in HIV prevention and vaccine research in resource-limited settings. AB - HIV prevention research has been facing increasing ethical and operational challenges. Factors influencing the design and conduct of HIV prevention trials include a rapidly changing evidence base, new biomedical prevention methods and modalities being tested, a large diversity of countries, sites and populations affected by HIV and participating in trials, and challenges of developing and making available products that will be feasible and affordable for at-risk populations. To discuss these challenges, a meeting, Ethical considerations around novel combination prevention modalities in HIV prevention and vaccine trials in resource-limited settings, was convened by NIH/NIAID/Division of AIDS on April 22-23, 2013. Several themes emerged from the meeting: (1) because of both trial design and ethical complexities, choosing prevention packages and designing combination prevention research trials will need to be evaluated on a case by case basis in different clinical trials, countries, and health systems; (2) multilevel stakeholder engagement from the beginning is vital to a fair and transparent process and also to designing ethical and relevant trials; (3) research should generally be responsive to a host country's needs, and sponsors and stakeholders should work together to address potential barriers to future access; and finally, (4) another meeting including a broader group of stakeholders is needed to address many of the outstanding ethical issues raised by this meeting. We offer an overview of the meeting and the key discussion points and recommendations to help guide the design and conduct of future HIV prevention and vaccine research in resource-limited settings. PMID- 25117933 TI - Improvement of ligninolytic properties by recombinant expression of glyoxal oxidase gene in hyper lignin-degrading fungus Phanerochaete sordida YK-624. AB - Glyoxal oxidase (GLOX) is a source of the extracellular H2O2 required for the oxidation reactions catalyzed by the ligninolytic peroxidases. In the present study, the GLOX-encoding gene (glx) of Phanerochaete chrysosporium was cloned, and bee2 promoter of P. sordida YK-624 was used to drive the expression of glx. The expression plasmid was transformed into a P. sordida YK-624 uracil auxotrophic mutant (strain UV-64), and 16 clones were obtained as GLOX introducing transformants. These transformants showed higher GLOX activities than wild-type P. sordida YK-624 and control transformants harboring marker plasmid. RT-PCR analysis indicated that the increased GLOX activity was associated with elevated recombinant glx expression. Moreover, these transformants showed higher ligninolytic activity than control transformants. These results suggest that the ligninolytic properties of white-rot fungi can be improved by recombinant expression of glx. PMID- 25117934 TI - Molecular sensing using armchair graphene nanoribbon. AB - In molecular electronics, the conductance strongly depends on the frontier energy levels and spatial orientations of molecules. Utilizing these features, we investigate the electron transport characteristics of conjugated molecules attached on an armchair graphene nanoribbon. The resulting sharp reduction in the transmission which represents molecular fingerprints and the change of the transmission depending on the molecular orientation, are examined in accordance with a unified picture of the Fano-Anderson model. These characteristics, being unique for each molecule, would be applicable to molecular recognition and configurational analysis. PMID- 25117929 TI - Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine. AB - BACKGROUND: Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria. METHODS: We examined changes in urine protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART naive participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121) with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz. RESULTS: At baseline, 18% of participants had clinically significant proteinuria (UPCR >=200 mg/g), and 11% had clinically significant albuminuria (UACR >=30 mg/g). The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups. In intention-to-treat analyses, there was a significant effect of NRTI component on fold change in UPCR (P = 0.011) and UACR (P = 0.018) from baseline to week 96, with greater improvements in participants randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on fold change in UPCR (P = 0.23) or UACR (P = 0.88), and no significant interactions between NRTI and NNRTI/PI components. CONCLUSIONS: In this prespecified secondary analysis, ART initiation was associated with improvements in proteinuria and albuminuria, with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC. These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens. Future studies should consider the long-term clinical significance of these findings. PMID- 25117931 TI - Self-assembly and release of peste des petits ruminants virus-like particles in an insect cell-baculovirus system and their immunogenicity in mice and goats. AB - Peste des petits ruminants (PPR) is an acute, febrile, viral disease of small ruminants that has a significant economic impact. For many viral diseases, vaccination with virus-like particles (VLPs) has shown considerable promise as a prophylactic approach; however, the processes of assembly and release of peste des petits ruminants virus (PPRV) VLPs are not well characterized, and their immunogenicity in the host is unknown. In this study, VLPs of PPRV were generated in a baculovirus system through simultaneous expression of PPRV matrix (M) protein and hemaglutin in (H) or fusion (F) protein. The released VLPs showed morphology similar to that of the native virus particles. Subcutaneous injection of these VLPs (PPRV-H, PPRV-F) into mice and goats elicited PPRV-specific IgG production, increased the levels of virus neutralizing antibodies, and promoted lymphocyte proliferation. Without adjuvants, the immune response induced by the PPRV-H VLPs was comparable to that obtained using equivalent amounts of PPRV vaccine. Thus, our results demonstrated that VLPs containing PPRV M protein and H or F protein are potential "differentiating infected from vaccinated animals" (DIVA) vaccine candidates for the surveillance and eradication of PPR. PMID- 25117932 TI - Rab11 regulates E-cadherin expression and induces cell transformation in colorectal carcinoma. AB - BACKGROUND: In the process of epithelial mesenchymal transition EMT, the disassembly of junctional adhesion complexes such as E-cadherin is a remarkable sign during changes in cell morphology and polarity. However, E-cadherin expression is dynamic, and is regulated by the cellular endocytic system; it is also involved in cell signaling mechanisms. In this study, we investigated the role of E-cadherin in colorectal tumors and the relationship with recycling endosome protein Rab11 in colon cell transformation. METHODS: For tissue screening, the expressions of E-cadherin and Rab11 in colorectal tumors were identified by immunohistochemistry in 113 patients with colorectal carcinoma. For the in vitro cell experiment, GFP-tagged Rab11 plasmid was transfected into HT29 colon cells, E-cadherin expression and cell transformation were monitored by Western blot and confocal microscopy. RESULTS: In immunohistochemistry, the mean score of E-cadherin in tumor and normal tissues was 1.41 +/- 0.06 and 1.08 +/- 0.06 (p < 0.05). The mean score of Rab11 in tumor and normal tissues was 0.51 +/- 0.05 and 0.18 +/- 0.02 (p < 0.05). Synchronous overexpression of E-cadherin and Rab11 was noted in 74 patients (66.5%) with colorectal carcinoma. When GFP-tagged Rab11 plasmid was overexpressed in cultured colon cell line HT-29, the E-cadherin expression was up-regulated, and cell membrane protrusion was induced, which resulted in cell transformation and cell migration. CONCLUSIONS: This study demonstrated the importance of the overexpression of Rab11 and E-cadherin in colorectal cancer. The results indicated that Rab11 together with E-cadherin might be potential markers for colorectal cancer progression and treatment. PMID- 25117935 TI - Comparison of root transcriptomes and expressions of genes involved in main medicinal secondary metabolites from Bupleurum chinense and Bupleurum scorzonerifolium, the two Chinese official Radix bupleuri source species. AB - Radix bupleuri, roots of Bupleurum species, is a widely used traditional Chinese medicine. Here, we compared the root transcriptomes of both Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. A total of 313 483 and 342 263 high quality expressed sequence tags were obtained, respectively. In addition, 17 117 (59.2%) and 19 416 (62.8%) unigenes for B. chinense and B. scorzonerifolium had homologous genes in the opposite dataset. For B. chinense, Kyoto Encyclopedia of Genes and Genomes database (KEGG) annotation identified carbohydrate metabolism, energy metabolism and amino acid metabolism as the three highest groups in the metabolism category. For B. scorzonerifolium, the lipid metabolism group had the most unigenes. Genes that may participate in the biosynthesis of terpenoid, triterpenoid, sterol, lignan and flavonoids were identified according to their annotations. (Tri)terpenoid-related genes were predominantly found in B. chinense. The expressions of certain genes were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in the roots of the two species. A total of 558 putative transcription factors (TFs) and 137 transcriptional regulators (TRs) among 1364 TFs and 327 TRs, and 610 TFs and 129 TRs among 1600 TFs and 323 TRs were specific for B. chinense and B. scorzonerifolium, respectively. Our transcriptome comparison reflects the different types and proportions of metabolites synthesized by the two species. The data, especially, those genes involved in the biosynthesis of particular types of metabolites, will provide the basis for further investigations of the secondary metabolite repertoire of the two Bupleurum species, as well as other species from the genus of Bupleurum. PMID- 25117937 TI - Moderate temperature increase leads to disintegration of floating sludge and lower abundance of the filamentous bacterium Microthrix parvicella in anaerobic digesters. AB - Filamentous bacteria such as Microthrix parvicella can cause serious foaming and floating sludge problems in anaerobic digesters fed with sewage sludge. The sewage sludge and oil co-fermenting laboratory-scale biogas digesters in this study were fed with substrates from a foaming-prone full-scale biogas plant containing the filamentous bacterium M. parvicella. At 37 degrees C, in both pneumatically mixed digesters a highly viscous and approximately 3 cm thick floating sludge was observed. A gradual increase of the temperature from 37 degrees C to 56 degrees C led to a significant decrease in the floating sludge thickness, which correlated with a strong decrease in the abundance of M. parvicella in the digestate. Furthermore, the stepwise temperature increase allowed for an adaption of the microbial community and prevented process failure. The study indicates that already a moderate temperature increase from 37 degrees C to 41 degrees C might help to control the M. parvicella abundance in full scale biogas plants. PMID- 25117938 TI - When will the TBT go away? Integrating monitoring and modelling to address TBT's delayed disappearance in the Drammensfjord, Norway. AB - Despite a substantial decrease in the use and production of the marine antifouling agent tributyltin (TBT), its continuing presence in harbors remains a serious environmental concern. Herein a case study of TBT's persistence in the Drammensfjord, Norway, is presented. In 2005, severe TBT pollution was measured in the harbor of the Drammensfjord, with an average sediment concentration of 3387 MUg kg(-1). To chart natural recovery in the Drammensfjord, an extensive sampling campaign was carried out over six years (2008-2013), quantifying TBT in water, settling particles and sediments. The monitoring campaign found a rapid decrease in sediment TBT concentration in the most contaminated areas, as well as a decrease in TBT entering the harbor via rivers and urban runoff. Changes observed in the more remote areas of the Drammensfjord, however, were less substantial. These data, along with measured and estimated geophysical properties, were used to parameterize and calibrate a coupled linear water sediment model, referred to as the Drammensfjord model, to make prognosis on future TBT levels due to natural recovery. Unique to this type of model, the calibration was done using a Bayesian Monte Carlo (BMC) updating approach, which used monitoring data to calibrate predictions, as well as reduce the uncertainty of input parameters. To our knowledge, this is the first use of BMC updating to calibrate a model describing natural recovery in a lake/harbor type system. Prior to BMC updating, the non-calibrated model data agreed with monitoring data by a factor of 4.3. After BMC updating, the agreement was within a factor 3.2. The non calibrated model predicted an average sediment concentration in the year 2025 of 2.5 MUg kg(-1). The BMC calibrated model, however, predicted a higher concentration in the year 2025 of 16 MUg kg(-1). This discrepancy was mainly due to the BMC calibration increasing the estimated riverine and runoff TBT emission levels relative to the initial input levels. Future monitoring campaigns can be used for further calibration of emission levels, and a clearer prognosis of when natural recovery will remove TBT pollution. PMID- 25117936 TI - Utilization of a novel digital measurement tool for quantitative assessment of upper extremity motor dexterity: a controlled pilot study. AB - BACKGROUND: The current methods of assessing motor function rely primarily on the clinician's judgment of the patient's physical examination and the patient's self administered surveys. Recently, computerized handgrip tools have been designed as an objective method to quantify upper-extremity motor function. This pilot study explores the use of the MediSens handgrip as a potential clinical tool for objectively assessing the motor function of the hand. METHODS: Eleven patients with cervical spondylotic myelopathy (CSM) were followed for three months. Eighteen age-matched healthy participants were followed for two months. The neuromotor function and the patient-perceived motor function of these patients were assessed with the MediSens device and the Oswestry Disability Index respectively. The MediSens device utilized a target tracking test to investigate the neuromotor capacity of the participants. The mean absolute error (MAE) between the target curve and the curve tracing achieved by the participants was used as the assessment metric. The patients' adjusted MediSens MAE scores were then compared to the controls. The CSM patients were further classified as either "functional" or "nonfunctional" in order to validate the system's responsiveness. Finally, the correlation between the MediSens MAE score and the ODI score was investigated. RESULTS: The control participants had lower MediSens MAE scores of 8.09%+/-1.60%, while the cervical spinal disorder patients had greater MediSens MAE scores of 11.24%+/-6.29%. Following surgery, the functional CSM patients had an average MediSens MAE score of 7.13%+/-1.60%, while the nonfunctional CSM patients had an average score of 12.41%+/-6.32%. The MediSens MAE and the ODI scores showed a statistically significant correlation (r=-0.341, p<1.14*10-5). A Bland-Altman plot was then used to validate the agreement between the two scores. Furthermore, the percentage improvement of the the two scores after receiving the surgical intervention showed a significant correlation (r=-0.723, p<0.04). CONCLUSIONS: The MediSens handgrip device is capable of identifying patients with impaired motor function of the hand. The MediSens handgrip scores correlate with the ODI scores and may serve as an objective alternative for assessing motor function of the hand. PMID- 25117939 TI - The Comparison of Food and Supplement as Probiotic Delivery Vehicles. AB - Probiotics are live bacteria which have frequently been reported to be beneficial in preventing a wide range of diseases as well as playing a major role in treating the existing ailments. Thus far, a variety of probiotic products have been developed which can be categorized into two groups: probiotic foods and supplements. Both foods and supplements have been able to confer the health benefits claimed for them. However, it is not known which one can be clinically more efficient, and to the best of our knowledge, until now no research has been conducted to investigate this issue. The present review aims to discuss this matter, based on the evidence available in the literature. To do so, articles indexed in PubMed and ScienceDirect between 2000 and 2011 were reviewed. The articles included the clinical trials in which either foods or supplements were used to administer the probiotics to either patients suffering from different diseases or healthy subjects. Although both foods and supplements seem to have been efficient carriers for the beneficial bacteria, to generally promote public health in communities, probiotic foods appear to be preferred to probiotic supplements. PMID- 25117940 TI - Deficits in auditory frequency discrimination and speech recognition in cochlear implant users. AB - OBJECTIVES: Speech recognition varies considerably following cochlear implantation for reasons that are still poorly understood. Considering the role of frequency discrimination in normal speech recognition, the aim of this study was to investigate the association between deficits in auditory frequency discrimination and speech recognition in cochlear implant users. METHODS: Frequency discrimination thresholds and speech recognition were assessed in a group of 20 cochlear implant users and 16 normally hearing controls. RESULTS: Based on their results on the speech recognition task, the cochlear implant users were categorized either as proficient (n = 10) or non-proficient users (n = 10). The non-proficient cochlear implant users had poorer auditory frequency discrimination compared to the normal hearing participants and proficient cochlear implant users (both P < 0.05). No significant difference was found between the proficient cochlear implant users and the normally hearing group (P > 0.05). Furthermore, a bivariate correlation analysis revealed a relationship between speech recognition and frequency discrimination. CONCLUSIONS: The present findings suggest an association between auditory frequency discrimination and speech recognition proficiency in cochlear implant users. Although no causal link can be drawn from these data, possible reasons for this association are discussed. PMID- 25117941 TI - Experimental amine-epoxide sealer: a physicochemical study in comparison with AH Plus and EasySeal. AB - AIM: To compare selected physicochemical and biological properties of an experimental sealer with those of two commercially available sealers. METHODOLOGY: AH Plus and EasySeal were used as model materials for commercially available amine-epoxide sealers. They were mixed as stated by the manufacturer. The two components of experimental sealer EvoSeal A were mixed 1 : 1 vol%. The setting time was determined in two different ways: first, by setting of sealers in a temperature- and moisture-controlled environment followed by testing with a Gilmore needle and secondly, by oscillating measurements of setting behaviour using a rheometer. Differential scanning calorimetry (DSC) of the sealer was performed for comparison of thermal properties. Flow and film thickness were determined by applying pressures of 100 g and 15.3 kg, respectively, on the materials between two glass plates and measuring the diameters of the compressed sealer and the thickness with a micrometer gauge. Solubility of set materials was conducted by layering the samples with water, storing in a temperature- and humidity-controlled environment and evaporating the solvent. The solved sealer parts were then weighed. The radiopacity was measured in an X-ray experiment comparing radiopacity of a cured sealer to an aluminium step wedge. Volume shrinkage was defined by measuring the densities of samples before and after setting. The film thickness, fluidity, curing time, radiopacity and solubility of the test materials were performed as specified in DIN EN ISO 6876:2010 draft. The volume shrinkage was determined in a method adapted from standard DIN 13907:2007 01. Antibacterial activity was tested against Gram-positive Streptococcus oralis cultures in a contact test based on standard ISO 22196:2011 (E). Statistical analysis was performed using Mann-Whitney U-test where applicable. Significant differences were determined with P < 0.05. RESULTS: The experimental sealer, EvoSeal A, reached standard specifications. In terms of film thickness, the highest value was measured for EvoSeal A with a film thickness of 27 MUm, comparing to 6 MUm for EasySeal (P <= 0.001) and 8 MUm for AH Plus (P <= 0.001). Comparing the flow, all values corresponded to EasySeal with a diameter of 17.3 mm. The only significant difference was determined for AH Plus compared to EvoSeal A (P = 0.0353). Volume shrinkage of EvoSeal A was 48% smaller compared to EasySeal and approximately 20% lower compared to AH Plus. The shortest curing time was determined for EvoSeal A (3.0 h) followed by EasySeal (4.1 h) and AH Plus (24 h). For all groups, significant differences were observed (P <= 0.001). EvoSeal A had a significantly higher radiopacity than EasySeal (P <= 0.001) but significantly lower values than AH Plus (P <= 0.001). The solubility of AH Plus and EvoSeal A was <0.5% (P = 0.2435). Compared to EasySeal with a solubility of 2.7%, significant differences were observed (P <= 0.02). Three weeks after setting, EasySeal and EvoSeal A still had an antibacterial effect against S. oralis in contrast to AH Plus. In this respect, comparing AH Plus with EvoSeal A and EasySeal, respectively, significant differences were observed (P <= 0.001). No significant differences between EasySeal with EvoSeal A (P = 0.540) were determined. CONCLUSIONS: The physical and chemical properties of the experimental sealer EvoSeal A were comparable to the two commercially established sealers EasySeal and AH Plus. PMID- 25117942 TI - Barriers to physical activity in chronic hemodialysis patients: a single-center pilot study in an Italian dialysis facility. AB - BACKGROUND/AIMS: In patients on chronic dialysis a sedentary lifestyle is a strong, yet potentially modifiable, predictor of mortality. The present single center pilot study evaluated social, psychological and clinical barriers that may hinder physical activity in this population. METHODS: We explored the association between barriers to physical activity and sedentarism in adult patients at a chronic dialysis facility in Parma, Italy. We used different questionnaries exploring participation in physical activity, physical functioning, patient attitudes and preferences, and barriers to physical activity perceived by either patients or dialysis doctors and nurses. RESULTS: We enrolled 104 patients, (67 males, 65%), mean age 69 years (79% of patients older than 60 years); median dialysis vintage 60 months (range 8-440); mean Charlson score 5.55, ADL (Activities of Daily Living) score 5.5. Ninety-two participants (88.5%) reported at least one barrier to physical activity. At multivariable analysis, after adjusting for age and sex, feeling to have too many medical problems (OR 2.99, 95% CI 1.27 to 7.07; P=0.012), chest pain (OR 10.78, 95% CI 1.28 to 90.28; P=0.029) and sadness (OR 2.59, 95% CI 1.10 to 6.09; P=0.030) were independently associated with physical inactivity. Lack of time for exercise counseling and the firm belief about low compliance/interest by the patients toward exercise were the most frequent barriers reported by doctors and nurses. CONCLUSION: We identified a number of patient-related and health personnel-related barriers to physical activity in patients on chronic dialysis. Solutions for these barriers should be addressed in future studies aimed at increasing the level of physical activity in this population. PMID- 25117943 TI - Airway pH monitoring in patients with suspected obstructive sleep apnoea using the Dx-pH oropharyngeal probe: preliminary report of a prospective cohort study. AB - OBJECTIVES: To investigate the laryngopharyngeal reflux (LPR) episodes and pH values in patients with suspected obstructive sleep apnoea (OSA) using the Dx-pH oropharyngeal probe. DESIGN: Prospective cohort study. SETTING: Tertiary medical centre. PARTICIPANTS: Forty patients with complaint of snoring or suspected OSA were prospectively enrolled to receive full nocturnal polysomnography (PSG). The patients were divided into 2 groups: a simple snorers group if the Respiratory Disturbance Index (RDI) was < 5 and an OSA group if the RDI was >= 5. MAIN OUTCOME MEASURES: The patients simultaneously received Dx-pH oropharyngeal probe monitoring for 12 h from about 6 pm to 6 am of the next day. The number of LPR events was recorded if the nadir of rapid pH drops was below pH 5.0 and 5.5. The difference of LPR events between the two groups and the difference of LPR events between awake and sleep periods in each group were analysed, respectively. RESULTS: There were 18 (45%) patients diagnosed as OSA with a mean RDI of 28.7, and 22 patients (55%) diagnosed as simple snorers. Between 2 groups, there were no significant differences in the LPR events and pH values during the awake period, sleep period or overall recording period. Comparison of the LPR events and minimum pH values between the awake period and the sleep period revealed there were no significant differences in either group. CONCLUSION: Using the new sensitive Dx-pH oropharyngeal probe with PSG, we found that OSA does not correlate with a higher incidence of LPR episodes. PMID- 25117949 TI - Comparative investigation of in vitro biotransformation of 14 components in Ginkgo biloba extract in normal, diabetes and diabetic nephropathy rat intestinal bacteria matrix. AB - Most herbal medicines will be metabolized by intestinal bacteria in the gastrointestinal tract before absorbed by the small intestine. Ginkgo biloba extract (GBE) possesses protective effects on the glomerulosclerosis of diabetic nephropathy (DN), but its biotransformation in diabetes and DN intestinal bacteria has not yet been recognized. In this work, a validated liquid chromatography-tandem mass spectrometry (LC-MS) method was established for the simultaneous quantification of 14 components in GBE in rat intestinal bacteria matrix, namely ginkgolides A, ginkgolides B, ginkgolides C, bilobalide, rutin, myricetin, quercitrin, quercetin, luteolin, genistein, kaempferol, apigenin, isorhamnetin and genkwanin. Chromatographic separation was performed on a Kromasil-C18 (4.6mm*250mm i.d., 5.0MUm) analytical column maintained at 35 degrees C. The mobile phase was a mixture of methanol (A) and 0.1% formic acid in water (B) with a step linear gradient at a flow rate of 1.0mlmin(-1). The calibration curves of these 14 analytes demonstrated good linearity within the test range (R>0.99). This validated method has successfully been applied into the pharmacokinetic study of the 14 components. More importantly, in the pharmacokinetic study, by comparing the time course of the biotransformation by normal, diabetes and DN rat intestinal bacteria, we found that the biotransformation speed and residence time of the 14 compounds in diabetes and DN rats differed obviously from that obtained in normal group, which provided valuable chemical information for further pharmacology and active mechanism research on GBE. PMID- 25117950 TI - Development of a stability-indicating HPLC method of etifoxine with characterization of degradation products by LC-MS/TOF, 1H and 13C NMR. AB - This paper describes a new LC-MS/TOF method for the degradation products determination when Etifoxine (ETI) is submitted to different stress conditions. Chromatography is performed by using Kromasil C18 column (250mm*4.6mm, 5MUm particle size). The selected mobile phase consists of formate buffer 0.02M, pH 3 and methanol (70/30, v/v). ETI is submitted to oxidative, acidic, basic, hydrolytic, thermal and UV light degradations. Detection is made at 254nm by photodiode array detector and mass spectrometry. A number of degradation products (DPs) called DPA, DPB, DPC and DPD are found depending on the stress; DPA with heat, DPA and DPB in acidic media or under UV-light; DPA, DPB and DPC under basic stress; DPA, DPB, DPC and DPD with oxidation. LC-MS/TOF is used to characterize the four DPs of ETI resulting from different stress conditions. (1)H and (13)C NMR are used to confirm the DP structures. The ETI fragmentation pathway is proposed. The method is validated with reference to International Conference on Harmonization guidelines and ETI are selectively determined in presence of its DPs, demonstrating its stability-indicating nature. Finally, for the validation step, specificity, linearity, accuracy and precision are determined for ETI and its DPs. PMID- 25117951 TI - Nanomechanical properties of poly(lactic-co-glycolic) acid film during degradation. AB - Despite the potential applications of poly(lactic-co-glycolic) acid (PLGA) coatings in medical devices, the mechanical properties of this material during degradation are poorly understood. In the present work, the nanomechanical properties and degradation of PLGA film were investigated. Hydrolysis of solvent cast PLGA film was studied in buffer solution at 37 degrees C. The mass loss, water uptake, molecular weight, crystallinity and surface morphology of the film were tracked during degradation over 20 days. Characterization of the surface hardness and Young's modulus was performed using the nanoindentation technique for different indentation loads. The initially amorphous films were found to remain amorphous during degradation. The molecular weight of the film decreased quickly during the initial days of degradation. Diffusion of water into the film resulted in a reduction in surface hardness during the first few days, followed by an increase that was due to the surface roughness. There was a significant delay between the decrease in the mechanical properties of the film and the decrease in the molecular weight. A sudden decline in mechanical properties indicated that significant bulk degradation had occurred. PMID- 25117953 TI - New series of avenanthramides in oat seed. AB - Avenanthramides are characteristic constituents of oat seeds. We analyzed the methanol extract of oat seeds by HPLC and detected three compounds 1, 2, and 3 eluted at retention times similar to avenanthramides. The three compounds were purified by column chromatography and HPLC. Spectroscopic analyses of 1, 2, and 3 suggested that they are amides of 4,5-dihydroxyanthranilic acid with caffeic, p coumaric, and ferulic acids, respectively. Their identities were confirmed by comparing spectra and chromatographic behavior with compounds synthesized from 4,5-dihydroxyanthranilic acid and N-hyrdroxysuccinimide esters of hydroxycinnamic acids. LC-MS/MS analysis with multiple reaction monitoring showed that the amounts of 1, 2, and 3 were 16.5-26.9% of corresponding avenanthamides with 5 hydroxyanthranilic acid. Compounds 1, 2, and 3 showed stronger 2,2-diphenyl-1 picrylhydrazyl (DPPH) radical-scavenging activity than the corresponding avenanthramides with 5-hydroxyanthranilic acid, indicating the involvement of 4,5 dihydroxyanthranilic acid moiety in the scavenging of DPPH radicals. PMID- 25117954 TI - Illuminating the origins of spectral properties of green fluorescent proteins via proteochemometric and molecular modeling. AB - Green fluorescent protein (GFP) has immense utility in biomedical imaging owing to its autofluorescent nature. In efforts to broaden the spectral diversity of GFP, there have been several reports of engineered mutants via rational design and random mutagenesis. Understanding the origins of spectral properties of GFP could be achieved by means of investigating its structure-activity relationship. The first quantitative structure-property relationship study for modeling the spectral properties, particularly the excitation and emission maximas, of GFP was previously proposed by us some years ago in which quantum chemical descriptors were used for model development. However, such simplified model does not consider possible effects that neighboring amino acids have on the conjugated pi-system of GFP chromophore. This study describes the development of a unified proteochemometric model in which the GFP chromophore and amino acids in its vicinity are both considered in the same model. The predictive performance of the model was verified by internal and external validation as well as Y-scrambling. Our strategy provides a general solution for elucidating the contribution that specific ligand and protein descriptors have on the investigated spectral property, which may be useful in engineering novel GFP variants with desired characteristics. PMID- 25117952 TI - Antibody-functionalized peptidic membranes for neutralization of allogeneic skin antigen-presenting cells. AB - We report herein application of an in situ material strategy to attenuate allograft T cell responses in a skin transplant mouse model. Functionalized peptidic membranes were used to impede trafficking of donor antigen-presenting cells (dAPCs) from skin allografts in recipient mice. Membranes formed by self assembling peptides (SAPs) presenting antibodies were found to remain underneath grafted skins for up to 6 days. At the host-graft interface, dAPCs were targeted by using a monoclonal antibody that binds to a class II major histocompatibility complex (MHC) molecule (I-A(d)) expressed exclusively by donor cells. Using a novel cell labeling near-infrared nanoemulsion, we found more dAPCs remained in allografts treated with membranes loaded with anti-I-A(d) antibodies than without. In vitro, dAPCs released from skin explants were found adsorbed preferentially on anti-I-A(d) antibody-loaded membranes. Recipient T cells from these mice produced lower concentrations of interferon-gamma cultured ex vivo with donor cells. Taken together, the data indicate that the strategy has the potential to alter the natural course of rejection immune mechanisms in allogeneic transplant models. PMID- 25117955 TI - Macular hole secondary to Valsalva retinopathy after doing push-up exercise. AB - BACKGROUND: Valsalva retinopathy and traumatic macular hole are common conditions, but macular hole secondary to Valsalva retinopathy is rarely reported. CASE PRESENTATION: A 34-year-old healthy man suffered Valsalva retinopathy after doing push-up exercise. During his follow-up visits, the best corrected visual acuity (BCVA) measurements, fundus examinations and spectral domain optical coherence tomography (SD-OCT) tests were performed. Three months later, the premacular hemorrhage was noticeably absorbed with an improvement of visual acuity. SD-OCT showed a lamellar macular hole with intact but thickened internal limiting membrane (ILM) with vitreal tractions on surface of the macular. Nine months after the first visit, his vision acuity was 20/25. The fundus examination showed a complete absorption of the macular hemorrhage. SD-OCT showed that the lamellar macular hole has enlarged, with thickened ILM on the surface. Seventeen months after the onset, the BCVA, fundus examination results and OCT findings were stable. CONCLUSIONS: Macular hole secondary to Valsalva retinopathy had been rarely reported and its mechanism needs further understanding. SD-OCT can be used to observe the evolvement of Valsalva retinopathy. PMID- 25117956 TI - HIV/AIDS and noncommunicable disease comorbidities: emerging research priorities. PMID- 25117958 TI - HIV and noncommunicable disease comorbidities in the era of antiretroviral therapy: a vital agenda for research in low- and middle-income country settings. AB - In this special 2014 issue of JAIDS, international investigator teams review a host of noncommunicable diseases (NCDs) that are often reported among people living and aging with HIV in sub-Saharan Africa. With the longer lifespans that antiretroviral therapy programs have made possible, NCDs are occurring due to a mix of chronic immune activation, medication side effects, coinfections, and the aging process itself. Cancer; cardiovascular and pulmonary diseases; metabolic, body, and bone disorders; gastrointestinal, hepatic, and nutritional aspects; mental, neurological, and substance use disorders; and renal and genitourinary diseases are discussed. Cost-effectiveness, key research methods, and issues of special importance in Asia, Latin America, and the Caribbean are also addressed. In this introduction, we present some of the challenges and opportunities for addressing HIV and NCD comorbidities in low- and middle-income countries, and preview the research agenda that emerges from the articles that follow. PMID- 25117959 TI - HIV and metabolic, body, and bone disorders: what we know from low- and middle income countries. AB - Globally, the HIV epidemic is evolving. Life expectancy for HIV-infected individuals has been extended because of more effective and more widely available antiretroviral therapy. As a result, chronic noncommunicable diseases (NCDs) have become important comorbid conditions. In particular, HIV-infected persons are increasingly at risk of developing metabolic (diabetes, dyslipidemias), body composition (lipodystrophy, overweight/obesity) and bone mineral density abnormalities. We have summarized the published epidemiological and clinical literature regarding these HIV-NCD comorbidities in low- and middle-income countries (LMICs). We found important gaps in knowledge. Specifically, there are few studies that use standardized methods and metrics; consequently, prevalence or incidence data are not comparable. There are very little or no data regarding the effectiveness or cost-effectiveness of clinical monitoring or therapeutic interventions for metabolic disorders in HIV-infected individuals. Also, although NCDs continue to grow in the HIV-negative population of most LMICs, there are few data comparing the incidence of NCD comorbidities between HIV-infected and HIV negative populations. To address these gaps, we describe potential research and capacity development priorities for the future. PMID- 25117957 TI - Challenges in the detection, prevention, and treatment of HIV-associated malignancies in low- and middle-income countries in Africa. AB - Cancers associated with immunosuppression and infections have long been recognized as a major complication of HIV/AIDS. More recently, persons living with HIV are increasingly diagnosed with a wider spectrum of HIV-associated malignancies (HIVAM) as they live longer on combination antiretroviral therapy. This has spurred research to characterize the epidemiology and determine the optimal management of HIVAM with a focus on low-and middle-income countries (LMICs). Given background coinfections, environmental exposures, host genetic profiles, antiretroviral therapy usage, and varying capacities for early diagnosis and treatment, one can expect the biology of cancers in HIV-infected persons in LMICs to have a significant impact on chronic HIV care, as is now the case in high-income countries. Thus, new strategies must be developed to effectively prevent, diagnose, and treat HIVAM in LMICs; provide physical/clinical infrastructures; train the cancer and HIV workforce; and expand research capacity-particularly given the challenges posed by the limitations on available transportation and financial resources and the population's general rural concentration. Opportunities exist to extend resources supported by the President's Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, Tuberculosis, and Malaria to improve the health-care infrastructure and train the personnel required to prevent and manage cancers in persons living with HIV. These HIV chronic care infrastructures could also serve cancer patients regardless of their HIV status, facilitating long-term care and treatment for persons who do not live near cancer centers, so that they receive the same degree of care as those receiving chronic HIV care today. PMID- 25117961 TI - Mental, neurological, and substance use disorders in people living with HIV/AIDS in low- and middle-income countries. AB - Depression, alcohol use disorders (AUD), and neurocognitive disorders are the 3 most prevalent mental, neurological, and substance use disorders in people living with HIV infection in low- and middle-income countries (LMICs). Importantly, they have an impact on everyday functions and on HIV outcomes. Many LMICs have validated tools to screen for and diagnose depression and AUD in the general population that can be used among people living with HIV infection. Current screening and diagnostic methods for HIV-associated neurocognitive disorders in the era of antiretroviral therapy are suboptimal and require further research. In our view, 2 research priorities are most critical. One is the development of an integrated screening approach for depression, AUD, and neurocognitive disorders that can be used by nonspecialists in LMICs. Second, research is needed on interventions for depression and AUD that also target behavior change, as these could impact on adherence to antiretroviral therapy and improve mental symptoms. Mentorship and fellowship schemes at an individual and institutional level need to be further supported to build capacity and provide platforms for research on HIV and mental, neurological, and substance use disorders in LMICs. PMID- 25117962 TI - HIV-associated renal and genitourinary comorbidities in Africa. AB - With the recent massive scale-up of access to antiretroviral therapy (ART) in resource-limited countries, HIV has become a chronic disease with new challenges. There is mounting evidence of an increased burden of renal and genitourinary diseases among HIV-infected persons caused by direct HIV viral effects and/or indirectly through the development of opportunistic infections, ART medication related toxicities, and other noncommunicable diseases (NCDs). We review the epidemiology of HIV-associated renal and urogenital diseases, including interactions with kidney-related NCDs such as hypertension, diabetes mellitus, and cardiovascular disease. We also examine the current evidence regarding the impact of HIV infection on the development of urogenital diseases. Highly advisable in sub-Saharan Africa are the establishment of renal disease registries, reviews of existing clinical practice including cost-effectiveness studies, and the adoption and use of HIV-related NCD management, with training for different cadres of health providers. Epidemiological research priorities include prospective studies to evaluate the true prevalence and spectrum of HIV related renal disease and their progression. Simple diagnostics tools should be evaluated, including urinary dipsticks and point-of-care urea and creatinine tests to screen for kidney injury in primary care settings. Study of urological manifestations of HIV can help determine the extent of disease and outcomes. As patients live longer on ART, the burden of renal and genitourological complications of HIV and of ART can be expected to increase with a commensurate urgency in both discovery and evidence-based improvements in clinical management. PMID- 25117960 TI - HIV and noncommunicable cardiovascular and pulmonary diseases in low- and middle income countries in the ART era: what we know and best directions for future research. AB - With the advent of effective antiretroviral therapy (ART), HIV is becoming a chronic disease. HIV-seropositive (+) patients on ART can expect to live longer and, as a result, they are at risk of developing chronic noncommunicable diseases related to factors, such as aging, lifestyle, long-term HIV infection, and the potential adverse effects of ART. Although data are incomplete, evidence suggests that even in low- and middle-income countries (LMICs), chronic cardiovascular and pulmonary diseases are increasing in HIV-positive patients. This review summarizes evidence-linking HIV infection to the most commonly cited chronic cardiovascular and pulmonary conditions in LMICs: heart failure, hypertension, coronary artery disease/myocardial infarction, stroke, obstructive lung diseases, and pulmonary arterial hypertension. We describe the observed epidemiology of these conditions, factors affecting expression in LMICs, and key populations that may be at higher risk (ie, illicit drug users and children), and finally, we suggest that strategic areas of research and training intended to counter these conditions effectively. As access to ART in LMICs increases, long-term outcomes among HIV-positive persons will increasingly be determined by a range of associated chronic cardiovascular and pulmonary complications. Actions taken now to identify those conditions that contribute to long-term morbidity and mortality optimize early recognition and diagnosis and implement effective prevention strategies and/or disease interventions are likely to have the greatest impact on limiting cardiovascular and pulmonary disease comorbidity and improving population health among HIV-positive patients in LMICs. PMID- 25117966 TI - HIV and noncommunicable diseases (NCDs) in Latin America: a call for an integrated and comprehensive response. AB - The life expectancy of people living with HIV has dramatically improved with the much increased access to antiretroviral therapy. Consequently, a larger number of people living with HIV are living longer and facing the increased burden of noncommunicable diseases (NCDs). NCDs and HIV infection share common epidemiologic and sociodemographic characteristics that influence their outcomes, which may be difficult to address in the relatively weak health systems of the region. Data on the prevalence and interactions of NCDs and HIV in Latin American countries remain very limited, which hinders their governments' ability to make informed decisions about health care policies. Therefore, there is an urgent need to develop a research agenda that will be the basis for an integrated and comprehensive health care approach to HIV and NCD comorbidities in Latin America. PMID- 25117964 TI - Observational research on NCDs in HIV-positive populations: conceptual and methodological considerations. AB - Noncommunicable diseases (NCDs) account for a growing burden of morbidity and mortality among people living with HIV in low- and middle-income countries (LMICs). HIV infection and antiretroviral therapy interact with NCD risk factors in complex ways, and research into this "web of causation" has so far been largely based on data from high-income countries. However, improving the understanding, treatment, and prevention of NCDs in LMICs requires region specific evidence. Priority research areas include: (1) defining the burden of NCDs among people living with HIV, (2) understanding the impact of modifiable risk factors, (3) evaluating effective and efficient care strategies at individual and health systems levels, and (4) evaluating cost-effective prevention strategies. Meeting these needs will require observational data, both to inform the design of randomized trials and to replace trials that would be unethical or infeasible. Focusing on Sub-Saharan Africa, we discuss data resources currently available to inform this effort and consider key limitations and methodological challenges. Existing data resources often lack population based samples; HIV-negative, HIV-positive, and antiretroviral therapy-naive comparison groups; and measurements of key NCD risk factors and outcomes. Other challenges include loss to follow-up, competing risk of death, incomplete outcome ascertainment and measurement of factors affecting clinical decision making, and the need to control for (time-dependent) confounding. We review these challenges and discuss strategies for overcoming them through augmented data collection and appropriate analysis. We conclude with recommendations to improve the quality of data and analyses available to inform the response to HIV and NCD comorbidity in LMICs. PMID- 25117963 TI - Noncommunicable diseases in HIV infection in low- and middle-income countries: gastrointestinal, hepatic, and nutritional aspects. AB - The purpose of this review was to outline the interaction between HIV and noncommunicable diseases affecting the gastrointestinal (GI) tract, liver, and nutritional disorders in low- and middle-income countries (LMICs), and to identify research priorities. Noncommunicable GI tract disorders are only moderately influenced by HIV, and peptic ulceration is actually less common. However, the impact of HIV on GI cancers needs further investigation. HIV interacts strongly with environmental enteropathy, exacerbating malabsorption of nutrients and drugs. HIV has 2 major effects on noncommunicable liver disease: drug-induced liver injury and nonalcoholic fatty liver disease (particularly in persons of African genetic descent). The effect of HIV on nutrition was one of the first markers of the epidemic in the 1980s, and HIV continues to have major nutritional consequences. Childhood malnutrition and HIV frequently coexist in some regions, for example, southern Africa, resulting in powerful negative interactions with poorer responses to standard nutritional rehabilitation. HIV and nutritional care need to be better integrated, but many questions on how best to do this remain unanswered. Across the spectrum of GI, hepatic, and nutritional disorders in HIV infection, there is increasing evidence that the microbiome may play an important role in disease pathogenesis, but work in this area, especially in low- and middle-income countries, is in its infancy. PMID- 25117967 TI - HIV and noncommunicable diseases: the Asian perspective. AB - Asia is seeing a rise in noncommunicable diseases in their general population and among people living with HIV. Many Asians have low body weight, which can lead to higher plasma concentrations of antiretrovirals and, as a result, their toxicities. Examples are metabolic complications from protease inhibitors, chronic kidney disease from tenofovir, and hepatotoxicity from nevirapine. Asia has not only the highest burden of hepatitis B viral infection than any other continent but also a predominance of genotypes B and C, the latter associated with higher risk for hepatocellular carcinoma. HIV-associated neurocognitive disorders are equally common among Asians as other populations. Diastolic dysfunction and asymptomatic myocardial ischemia are not infrequent. Non-Hodgkin lymphoma is the most common AIDS-related cancer, whereas Kaposi sarcoma is relatively infrequent. Emerging data show high prevalence of human papillomavirus associated anal dysplasia in men who have sex with men. Resource-limited countries in Asia suffer from lack of resources for national screening programs of noncommunicable diseases, which, in turn, limits the epidemiologic data that exist to guide the use of national health resources. PMID- 25117968 TI - Phylogenetic relationships and pathogenicity variation of two Newcastle disease viruses isolated from domestic ducks in Southern China. AB - BACKGROUND: Newcastle disease (ND) is an OIE listed disease caused by virulent avian paramyxovirus type 1 (APMV-1) strains, which is enzootic and causes large economic losses in the poultry sector. Genotype VII and genotype IX NDV viruses were the predominant circulating genotype in China, which may possibly be responsible for disease outbreaks in chicken flocks in recent years. While ducks and geese usually have exhibited inapparent infections. METHODS: In the present study, we investigate the complete genome sequence, the clinicopathological characterization and transmission of two virulent Newcastle disease viruses, SS 10 and NH-10, isolated from domestic ducks in Southern China in 2010. RESULTS: F, and the complete gene sequences based on phylogenetic analysis demonstrated that SS-10 (genotype VII) and NH-10 (genotype IX) belongs to class II. The deduced amino acid sequence was (112)R-R-Q-K/R-R-F(117) at the fusion protein cleavage site. Animal experiment results showed that the SS-10 virus isolated from ducks was highly pathogenic for chickens and geese, but low pathogenic for ducks. It could be detected from spleen, lung, kidney, trachea, small intestine, bursa of fabricius, thymus, pancreas and cecal tonsils, oropharyngeal and cloacal swabs, and could transmit to the naive contact birds. Moreover, it could transmit to chickens, ducks and geese by naive contact. However, the NH-10 virus isolated from ducks could infect some chickens, ducks and geese, but only caused chickens to die. Additionally, it could transmit to the naive contact chickens, ducks, and geese. CONCLUSION: The two NDV isolates exhibited different biological properties with respect to pathogenicity and transmission in chickens, ducks and geese. Therefore, no species-preference exists for chicken, duck or goose viruses and more attention should be paid to the trans-species transmission of VII NDVs between ducks, geese and chickens for the control and eradication of ND. PMID- 25117969 TI - Plerixafor is effective given either preemptively or as a rescue strategy in poor stem cell mobilizing patients with multiple myeloma. AB - BACKGROUND: Harvest of more than one CD34+ stem cell transplant has become the standard, to ensure the option for a second autologous transplantation in patients with relapsed or progressive multiple myeloma (MM). Additional administration of the CXCR-4 inhibitor plerixafor has been shown to increase the efficiency of CD34+ stem cell harvest. However, the algorithm when to apply plerixafor is still under debate. STUDY DESIGN AND METHODS: In this retrospective study, 46 MM patients were categorized into four groups according to their CD34+ stem cell count in peripheral blood (PB) and mobilization with or without plerixafor: Group A comprised poor mobilizers with CD34+ cell counts of fewer than 20 * 10(6) /L in PB. Group B included inadequate mobilizers with CD34+ cell counts of 20 * 10(6) /L or more in PB and a low CD34+ stem cell yield in the first leukapheresis session. Patients receiving plerixafor preemptively (Group A1) and as a rescue strategy (Group B1) were compared to patients continuing stem cell collection with granulocyte-colony-stimulating factor alone (Groups A2 and B2). RESULTS: In both, the preemptive and the rescue settings, plerixafor enhanced the CD34+ stem cell yield significantly. Poor mobilization and administration of plerixafor was not associated with delayed engraftment. CONCLUSION: Our data demonstrate that administration of plerixafor is safe and effective and facilitates a significantly higher CD34+ stem cell harvest. Based on the presented data, we propose an algorithm for the use of plerixafor for CD34+ stem cell mobilization and harvesting in poor mobilizing myeloma patients. PMID- 25117970 TI - Bacteriocins: Recent Trends and Potential Applications. AB - In the modern era, there is great need for food preservation in both developing and developed countries due to increasing demand for extending shelf life and prevention of spoilage of food material. With the emergence of new pathogens and ability of micro-organisms to undergo changes, exploration of new avenues for the food preservation has gained importance. Moreover, awareness among consumers regarding harmful effects of chemical preservatives has been increased. Globally, altogether there is increasing demand by consumers for chemical-free and minimal processed food products. Potential of bacteriocin and its application in reducing the microbiological spoilages and in the preservation of food is long been recognized. Bacteriocins are normally specific to closely related species without disrupting the growth of other microbial populations. A number of applications of bacteriocin have been reported for humans, live stock, aquaculture etc. This review is focused on recent trends and applications of bacteriocins in different areas in addition to their biopreservative potential. PMID- 25117971 TI - Bacterial diversity in a contaminated Alpine glacier as determined by culture based and molecular approaches. AB - Glaciers are important ecosystems, hosting bacterial communities that are adapted to cold conditions and scarcity of available nutrients. Several works focused on the composition of bacterial communities in glaciers and on the long-range atmospheric deposition of pollutants in glaciers, but it is not clear yet if ski resorts can represent a source of point pollution in near-by glaciers, and if these pollutants can influence the residing bacterial communities. To test these hypotheses, 12 samples were analyzed in Madaccio Glacier, in a 3200 ma.s.l. from two areas, one undisturbed and one close to a summer ski resort that is active since the 1930s. Chemical analyses found concentrations up to 43 ng L(-1) for PCBs and up to 168 MUg L(-1) for PAHs in the contaminated area: these values are significantly higher than the ones found in undisturbed glaciers because of long range atmospheric deposition events, and can be explained as being related to the near-by ski resort activities. Isolation of strains on rich medium plates and PCR DGGE analyses followed by sequencing of bands allowed the identification of a bacterial community with phylogenetic patterns close to other glacier environments, with Proteobacteria and Actinobacteria the mostly abundant phyla, with Acidobacteria, Firmicutes and Cyanobacteria also represented in the culture independent analyses. A number of isolates were identified by molecular and biochemical methods as phylogenetic related to known xenobiotic-degrading strains: glaciers subjected to chemical contamination can be important reservoirs of bacterial strains with potential applications in bioremediation. PMID- 25117973 TI - Comparison of eSRTs and comfort levels in users of Digisonic SP cochlear implants. AB - OBJECTIVE: This project proposes to assess the relation between the electrical stapedius reflex threshold (eSRT) and comfort levels in users of the Digisonic SP cochlear implant. METHODS: Cross-sectional study, where eSRTs are compared to the comfort current levels at 2 weeks and at 1-year post-fitting in a group of 11 adults getting a significant improvement in open set speech recognition from a Digisonic SP cochlear implant. RESULTS: The linear relation between eSRTs and comfort levels results in Pearson correlation coefficients of 0.65 (P < 0.01; at 2 weeks) to 0.60 (P < 0.05; at 1 year). The comfort levels can be predicted from the eSRTs for the Digisonic SP device from the model equation C level = 19.12 + 0.41*eSRT within a clinically acceptable margin of error. DISCUSSION: Reflex thresholds could be obtained in most participants, and in most channels of the Digisonic implant. The equation model appears as a quite reliable predictor of comfort levels for users of this device. PMID- 25117972 TI - Evaluation of bifidobacterial community composition in the human gut by means of a targeted amplicon sequencing (ITS) protocol. AB - The precise appraisal of the composition of the human gut microbiota still represents a challenging task. The advent of next generation sequencing approaches has opened new ways to dissect the microbial biodiversity of this ecosystem through the use of 16S rRNA gene-based microbiota analysis approaches. However, the detailed representation of specific groups or members of the human gut microbiota, for example Bifidobacteria, may be skewed by the PCR primers employed in the amplification step of the 16S rRNA gene-based microbial profiling pipeline and by the limited resolution of the 16S rRNA gene variable regions. Here, we define the internal transcribed spacer (ITS) sequences of all currently known Bifidobacterium taxa, providing a Bifidobacterium-specific primer pair that targets a hypervariable region within the ITS suitable for precise taxonomic identification of all 48 so far recognized members of the Bifidobacterium genus. In addition, we present an optimized protocol for ITS-based profiling utilizing qiime software, allowing accurate and subspecies-specific compositional reconstruction of the bifidobacterial community in the human gut. PMID- 25117974 TI - Performance assessment of patient on dialysis. AB - Patients on dialysis are poorly active and show a low level of physical functioning. Questionnaires and objective measurements of spontaneous physical activity are available as well as complex-expensive or simple-unexpensive tests useful to assess the patient's exercise capacity. Performance assessment unravels patients' capabilities, enables a tailored exercise prescription and provides predictive information on main clinical outcomes and therefore this topic should be of interest for nephrologists. A routinary minimal pool of tests might be usefully performed in a dialysis centre to stratify the patient's risk and to recognize patients in need of exercise training in order to address them to community-based or rehabilitative programs. PMID- 25117965 TI - HIV, tuberculosis, and noncommunicable diseases: what is known about the costs, effects, and cost-effectiveness of integrated care? AB - Unprecedented investments in health systems in low- and middle-income countries (LMICs) have resulted in more than 8 million individuals on antiretroviral therapy. Such individuals experience dramatically increased survival but are increasingly at risk of developing common noncommunicable diseases (NCDs). Integrating clinical care for HIV, other infectious diseases, and NCDs could make health services more effective and provide greater value. Cost-effectiveness analysis is a method to evaluate the clinical benefits and costs associated with different health care interventions and offers guidance for prioritization of investments and scale-up, especially as resources are increasingly constrained. We first examine tuberculosis and HIV as 1 example of integrated care already successfully implemented in several LMICs; we then review the published literature regarding cervical cancer and depression as 2 examples of NCDs for which integrating care with HIV services could offer excellent value. Direct evidence of the benefits of integrated services generally remains scarce; however, data suggest that improved effectiveness and reduced costs may be attained by integrating additional services with existing HIV clinical care. Further investigation into clinical outcomes and costs of care for NCDs among people living with HIV in LMICs will help to prioritize specific health care services by contributing to an understanding of the affordability and implementation of an integrated approach. PMID- 25117975 TI - A comparison between amylase levels from peritonsillar, dental and neck abscesses. AB - OBJECTIVES: Pus of peritonsillar abscess (PTA) contains very high amylase levels in some patients. The objective of this study was to further test this finding and to check whether high amylase levels in peritonsillar abscess originate from contamination by saliva during aspiration. STUDY DESIGN: Prospective study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study includes 64 patients with PTA, 8 patients with a neck abscess and 12 patients with a dental abscess. MAIN OUTCOME MEASURE: Amylase levels of pus and serum were compared between the groups. Clinical data regarding hospitalisation length, recurrence rate and previous antibiotic treatment were also collected. RESULTS: Mean amylase levels in the pus of the PTA group were 3045 U/L (median 59 U/L), 13 U/L in the neck abscess group (P = 0.001) and 22 U/L in the dental abscess group (P = 0.001). Mean serum amylase was higher in the PTA group; PTA - 50 U/L, neck abscess - 37 U/L (P = 0.002) and dental abscess - 26 U/L (P < 0.002). All of the patients with amylase levels above 65 U/L had a first episode of PTA. In contrast, 40% of patients with amylase lower than 65 U/L had recurrent PTA (P = 0.003). CONCLUSION: A clear association is seen between minor salivary glands and peritonsillar abscess. The high amylase level in peritonsillar pus is not from contamination with saliva. PMID- 25117976 TI - The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its load with siderophore-bound iron. AB - The mechanisms of allergic sensitization to milk are still elusive. The major allergen Bos d 5 belongs to the lipocalin-family and thus is able to transport numerous ligands. In this study we investigated its ability to bind to iron siderophore complexes and tested the immune-modulatory properties of Bos d 5 in either forms. Structural and in silico docking analysis of Bos d 5 revealed that Bos d 5 is able to bind to iron via catechol-based flavonoids (quercetin, myricetin, luteolin) that act as siderophores as confirmed by spectral-analysis and iron staining. Calculated dissociation constants of docking analyses were below 1 uM by virtual addition of iron. When incubated with human peripheral blood mononuclear cells (PBMCs), only the apo-form of Bos d 5 led to an increase of CD4+positive cells and significantly elevated IL13 and IFNgamma-levels. In contrast, holo-Bos d 5 decreased numbers of CD4 expressing cells and induced apoptosis. Taken together, our data give evidence that Bos d 5 is capable of binding iron via siderophores. Moreover, our data support for the first time the notion that the form of application (apo- or holo-form) is decisive for the subsequent immune response. The apo-form promotes Th2 cells and inflammation, whereas the holo-form appears to be immunosuppressive. PMID- 25117977 TI - Mechanisms of glioma formation: iterative perivascular glioma growth and invasion leads to tumor progression, VEGF-independent vascularization, and resistance to antiangiogenic therapy. AB - As glioma cells infiltrate the brain they become associated with various microanatomic brain structures such as blood vessels, white matter tracts, and brain parenchyma. How these distinct invasion patterns coordinate tumor growth and influence clinical outcomes remain poorly understood. We have investigated how perivascular growth affects glioma growth patterning and response to antiangiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to commonly invade and proliferate within brain perivascular space. This form of brain tumor growth and invasion is also shown to characterize de novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma (GBM), and peripheral cancer metastasis to the human brain. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual glioma cells use perivascular space as a conduit for tumor invasion. Agent-based computational modeling recapitulated biological perivascular glioma growth without the need for neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular glioma by treating animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel normalization, yet failed to reduce tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas while exacerbating brain tumor invasion. Our results provide compelling experimental evidence in support of the recently described failure of clinically used antiangiogenics to extend the overall survival of human GBM patients. PMID- 25117978 TI - Co-treatment with panitumumab and trastuzumab augments response to the MEK inhibitor trametinib in a patient-derived xenograft model of pancreatic cancer. AB - Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and epidermal growth factor receptor (EGFR) family signaling are drivers of tumorigenesis in pancreatic ductal adenocarcinoma (PDAC). Previous studies have demonstrated that combinatorial treatment of PDAC xenografts with the mitogen-activated protein kinase-extracellular-signal-regulated kinase (ERK) kinase1/2 (MEK1/2) inhibitor trametinib and the dual EGFR/human epidermal growth factor receptor 2 (HER2) inhibitor lapatinib provided more effective inhibition than either treatment alone. In this study, we have used the therapeutic antibodies, panitumumab (specific for EGFR) and trastuzumab (specific for HER2), to probe the role of EGFR and HER2 signaling in the proliferation of patient-derived xenograft (PDX) tumors. We show that dual anti-EGFR and anti-HER2 therapy significantly augmented the growth inhibitory effects of the MEK1/2 inhibitor trametinib in three different PDX tumors. While significant growth inhibition was observed in both KRAS mutant xenograft groups receiving trametinib and dual antibody therapy (tumors 366 and 608), tumor regression was observed in the KRAS wild-type xenografts (tumor 738) treated in the same manner. Dual antibody therapy in conjunction with trametinib was equally or more effective at inhibiting tumor growth and with lower apparent toxicity than trametinib plus lapatinib. Together, these studies provide further support for a role for EGFR and HER2 in pancreatic cancer proliferation and underscore the importance of therapeutic intervention in both the KRAS-rapidly accelerated fibrosarcoma kinase (RAF)-MEK-ERK and EGFR-HER2 pathways to achieve maximal therapeutic efficacy in patients. PMID- 25117979 TI - SAMSN1 is a tumor suppressor gene in multiple myeloma. AB - Multiple myeloma (MM), a hematological malignancy characterized by the clonal growth of malignant plasma cells (PCs) in the bone marrow, is preceded by the benign asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Several genetic abnormalities have been identified as critical for the development of MM; however, a number of these abnormalities are also found in patients with MGUS, indicating that there are other, as yet unidentified, factors that contribute to the onset of MM disease. In this study, we identify a Samsn1 gene deletion in the 5TGM1/C57BL/KaLwRij murine model of myeloma. In addition, SAMSN1 expression is reduced in the malignant CD138+ PCs of patients with MM and this reduced expression correlates to total PC burden. We identify promoter methylation as a potential mechanism through which SAMSN1 expression is modulated in human myeloma cell lines. Notably, re-expression of Samsn1 in the 5TGM1 murine PC line resulted in complete inhibition of MM disease development in vivo and decreased proliferation in stromal cell-PC co-cultures in vitro. This is the first study to identify deletion of a key gene in the C57BL/KaLwRij mice that also displays reduced gene expression in patients with MM and is therefore likely to play an integral role in MM disease development. PMID- 25117986 TI - Tissue vitamin concentrations are maintained constant by changing the urinary excretion rate of vitamins in rats' restricted food intake. AB - We previously reported that mild food restriction induces a reduction in tryptophan-nicotinamide conversion, which helps to explain why death secondary to pellagra is pandemic during the hungry season. In this study, we investigated the levels of B-group vitamins in the liver, kidney, blood, and urine in rats that underwent gradual restriction of food intake (80, 60, 40, and 20% restriction vs. ad libitum food intake). No significant differences in the B-group vitamin concentrations (mol/g tissue) in the liver and kidney were observed at any level of food restriction. However, the urine excretion rates exhibited some characteristic phenomena that differed by vitamin. These results show that the tissue concentrations of B-group vitamins were kept constant by changing the urinary elimination rates of vitamins under various levels of food restriction. Only vitamin B12 was the only (exception). PMID- 25117980 TI - Tumor interstitial fluid pressure-a link between tumor hypoxia, microvascular density, and lymph node metastasis. AB - High microvascular density (MVD) in the primary tumor has been shown to be associated with increased incidence of lymph node metastases and poor clinical outcome. Other investigations have revealed that a large fraction of hypoxic tissue in the primary tumor is associated with metastatic disease and impaired survival. These data are apparently incompatible because tumor hypoxia is primarily a consequence of poor oxygen supply caused by an inadequate vasculature with increased intervessel distances. Here, we provide an explanation of these observations. Human melanoma xenografts were used as preclinical cancer models. Tumors that metastasized to lymph nodes showed higher interstitial fluid pressure (IFP) than those that did not metastasize, and compared with tumors with low IFP, tumors with high IFP showed large hypoxic fractions centrally, high MVD in the periphery, high peritumoral density of lymphatics, and elevated expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C. Significant correlations were found between peripheral MVD and central hypoxia, and lymph node metastasis was associated with high values of both parameters. These findings suggest that the outcome of cancer may be associated with both high MVD and extensive hypoxia in the primary tumor. We propose that proangiogenic factors are upregulated in the tumor center and that the outward interstitial fluid flow caused by the elevated IFP transports these factors to the tumor surface where they evoke hemangiogenesis and lymphangiogenesis, and consequently, that the IFP serves as a link between tumor hypoxia, peripheral tumor hemangiogenesis, peritumoral lymphangiogenesis, and lymph node metastasis. PMID- 25117987 TI - Timing of complementary food introduction and age at diagnosis of type 1 diabetes: the SEARCH nutrition ancillary study (SNAS). AB - The association between timing of complementary food introduction and age at diagnosis of type 1 diabetes was investigated among 1077 children in the SEARCH for Diabetes in Youth study. Age at diagnosis was 5 months earlier for children introduced to sugar-sweetened beverages (SSB) in the first 12 months of life compared with those who were not (9.0+/-0.2 vs 9.5+/-0.1; P=0.02) independent of human leukocyte antigen (HLA) risk status. Analyses stratified by HLA risk status found that children with a high-risk HLA genotype had an earlier age at diagnosis if they were introduced to fruit juice in the first year of life (mean age at diagnosis=9.3+/-0.1, 9.1+/-0.1 and 9.6+/-0.2 for introduction at ?6 months, between 7 and 11 months and ?12 months, respectively; P=0.04). Introduction of SSB in the first year of life may accelerate the onset of type 1 diabetes independent of HLA risk status. PMID- 25117988 TI - Enteral nutrition within 72 h after onset of acute pancreatitis vs delayed initiation. AB - OBJECTIVES: To explore early (within 72 h) vs delayed enteral nutrition (EN) therapy for patients with acute pancreatitis (AP). SUBJECTS/METHODS: A total of 93 patients were allocated to two groups: early enteral nutrition (EEN) group (started within 72 h after onset) and delayed enteral nutrition (DEN) group (started beyond 72 h but within 7 days after onset). Baseline parameters and scores were recorded on admission and on day 3 after the initiation of EN therapy, as were the clinical outcome variables. RESULTS: Hospital mortality, length of stay, number of patients requiring mechanical ventilation and incidence of pancreatic infection in the EEN group were significantly lower than those in the DEN group; all six reported deaths were in the DEN group. In the DEN group, more patients suffered from sepsis, shock or acute kidney injury, and more patients required surgical intervention or continuous renal replacement therapy. On day 3 after EN therapy was initiated, the acute physiology and chronic health evaluation II scores, sequential organ failure assessment scores, C-reactive protein levels and the incidence of bowel wall thickening were lower in the EEN group than in the DEN group. The time when EN therapy was initiated was a prognostic variable for pancreatic infection (odds ratio, 24.08; P=0.014). CONCLUSIONS: Compared with the DEN therapy, EEN therapy can accelerate the recovery of disturbed homeostasis, reduce the incidence of pancreatic infection and improve the clinical outcomes of AP patients. For AP patients, EN therapy should be initiated within 72 h after onset. PMID- 25117989 TI - Dosimetric factors associated with weight loss during (chemo)radiotherapy treatment for lung cancer. AB - BACKGROUND/OBJECTIVES: Thoracic radiotherapy (RT) is associated with acute toxicities, including oesophagitis, which can have an impact on nutritional intake and subsequently lead to malnutrition. This study aimed to identify RT dosimetric factors associated with ?5% weight loss in patients receiving treatment for non-small-cell lung cancer (NSCLC). METHODS: Radiation dose data to the oesophagus (including mean, maximum dose and oesophageal length) were retrospectively analysed for a cohort of 54 NSCLC patients treated with concurrent chemoradiotherapy between 2004 and 2006. Weight change was calculated using the lowest weight during the 90 days from RT commencement compared with the start of RT. RESULTS: Four patients for whom weight was not available at the start or end of treatment were excluded, leaving 50 patients for analysis. The prevalence of significant weight loss during the 90 days from RT commencement was 22% (median weight loss=9.1%, range=5.9-22.1). Dosimetric factors significantly associated with ?5% weight loss were maximum dose to the oesophagus (P=0.046), absolute oesophageal length receiving 40 Gy (odds ratio (OR)=1.18, P=0.04), 50 Gy (OR=1.20, P=0.02) and 60 Gy (OR=1.32, P=0.005) to the partial circumference, relative oesophageal length receiving 50 Gy (OR=1.03, P=0.03) and 60 Gy (OR=1.07, P=0.005) to the partial circumference. CONCLUSIONS: Multiple dosimetric factors were associated with significant weight loss. Of these factors, absolute and relative length of the oesophagus receiving 60 Gy to the partial circumference were more strongly related. Understanding the dosimetric factors associated with weight loss may aid early identification and intervention in patients at nutritional risk. PMID- 25117990 TI - Body mass index and mild cognitive impairment-to-dementia progression in 24 months: a prospective study. AB - BACKGROUND/OBJECTIVES: Mild cognitive impairment (MCI), often considered as an early stage of dementia, is heterogeneous, and not all subjects with MCI progress into clinically diagnosed dementia. Low body weight (and body mass index, BMI) as well as losing weight while in MCI stadium have been proposed as possible risk factors of MCI-to-dementia conversion. SUBJECTS/METHODS: A prospective, 2-year observation of 102 MCI subjects has been conducted. Data on MCI subtype, somatic and neuropsychiatric co-morbidity and demographic characteristics (including age, gender and education), were collected. In addition, baseline and yearly BMI were calculated. RESULTS: Data of 83 out of the originally included 102 subjects were available after 2 years; 27 of those (32.5%) progressed to dementia. In univariate analysis, multiple-deficit MCI subtype (as compared with pure amnestic), higher age, the presence of diabetes and apathy, and lower baseline BMI (and losing weight on 2-year follow-up) were associated with conversion to dementia. Variables retained in the multivariate backward stepwise logistic regression model for conversion after 24 months of observation included lower baseline BMI (odds ratio, OR (95% cofidence interval, CI): 0.6 (0.4-0.9)), weight loss on 2-year follow-up (OR (95% CI): 1.3 (1.1-1.5)), male gender (OR (95% CI): 0.1 (0.01-0.9)) and presence of apathy (OR (95% CI): 70.7 (5.6-699)). Apathetic subjects had lower BMI and higher weight loss after controlling for potential confounders (age, gender, years of education and baseline ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) score). CONCLUSION: MCI subjects presenting with apathy, low initial BMI and losing weight on follow-up have a significantly greater risk of developing dementia. Nutritional and behavioural assessment should be considered as additional tools in evaluating the risk of dementia among MCI subjects. PMID- 25117991 TI - Effect of maternal n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on adiposity in childhood: a systematic review and meta-analysis of randomized controlled trials. AB - It is hypothesized that prenatal and early postnatal exposure to n-3 long-chain polyunsaturated fatty acids (LCPUFAs) is negatively associated with adiposity later in life. We conducted a systematic review and meta-analysis to evaluate whether maternal n-3 LCPUFA supplementation in pregnancy and/or lactation exerts a beneficial effect on adiposity status in childhood. We searched six electronic databases till 20 May 2014 for randomized controlled trials (RCTs) of n-3 LCPUFA supplementation to pregnant and/or lactating women that reported data on body mass index (BMI), waist circumference, sum of skinfold thicknesses or body fat mass in children. Adiposity measures were grouped into three age categories: preschool children (<5 years), school-aged children (6-12 years), and adolescents (>13 years). Trial quality was assessed. We conducted fixed-effect and random effects meta-analyses to combine study-specific estimates of differences between the supplemented and control groups. A total of 6 RCTs (9 publications) involving 2847 participants were included. Summary estimates showed no effect of maternal supplementation on BMI in preschool (standardized mean difference (SMD)=0.07, 95% confidence interval (CI)=-0.22, 0.36, P=0.65) and school-aged children (SMD=0.12, 95% CI=-0.06, 0.30, P=0.20). Because of sparse data, it was not possible to pool study results relating to other adiposity measures. There is currently no evidence to support that n-3 LCPUFA supplementation during pregnancy and/or lactation favourably affects child adiposity. Further high-quality trials are needed. PMID- 25117992 TI - Vitamin D status and associated factors of deficiency among Jordanian children of preschool age. AB - BACKGROUND/OBJECTIVES: Vitamin D deficiency in children remains a global concern. Although literature exists on the vitamin D status and its risk factors among children in the Middle East, findings have yielded mixed results, and large, representative community studies are lacking. SUBJECTS/METHODS: In a nationally representative survey of 1077 Jordanian children of preschool age (12-59 months) in Spring 2010, we measured 25(OH)D3 concentrations by liquid chromatography tandem mass spectrometry and calculated prevalence ratios for deficiency associated with various factors. RESULTS: RESULTS showed 19.8% (95% confidence interval (CI): 16.4-23.3%) deficiency (<12 ng/ml) and 56.5% (95% CI: 52.0-61.0%) insufficiency (<20 ng/ml). In adjusted models, prevalence of deficiency was higher for females compared with males (prevalence ratio (PR)=1.74, 95% CI: 1.22 2.47, P=0.002) and lower for children 24-35 months of age (PR=0.64, 95% CI: 0.44 0.92, P=0.018) compared with children 12-23 months of age. In rural areas, there was no difference in prevalence of vitamin D deficiency between those whose mothers had/did not have vitamin D deficiency (P=0.312); however, in urban areas, prevalence of vitamin D deficiency was 3.18 times greater among those whose mothers were vitamin D deficient compared with those whose mothers were not deficient (P=0.000). CONCLUSIONS: Vitamin D deficiency and insufficiency pose significant public health problems in Jordanian children with female children disproportionately affected. Strong associations between vitamin D status in children and urban residency and maternal vitamin D status suggest that the behaviors related to sun exposure in urban mothers likely also affect the sun exposure and thus vitamin D status of their children. PMID- 25117993 TI - Household food insecurity and dietary diversity as correlates of maternal and child undernutrition in rural Cambodia. AB - OBJECTIVES: To assess household food insecurity and dietary diversity as correlates of maternal and child anthropometric status and anemia in rural Cambodia. METHODS: Trained interviewers administered a survey to 900 households in four rural districts of Prey Veng, Cambodia. The Household Food Insecurity Access Scale (HFIAS) and Household Dietary Diversity Score (HDDS) were used to assess household food insecurity and dietary diversity. The height, weight and hemoglobin concentration of the mother and youngest child under 5 years in each household were measured. Multivariate logistic regression models were constructed to assess the association between household food insecurity and dietary diversity, and child stunting and wasting, maternal thinness, maternal and child anemia. RESULTS: The mean (s.d.) HFIAS and HDDS scores were 5.3 (3.9) and 4.7 (1.6), respectively. The respective prevalences of mild, moderate and severe food insecurity were 33, 37 and 12%. Maternal thinness, child stunting and child wasting were present in 14.6, 25.4 and 8.1% of respondents, respectively. The risk of maternal thinness, but not child stunting or wasting, increased as the severity of household food insecurity increased. Household food insecurity was also positively associated with maternal, but not child, anemia. Household dietary diversity status was not significantly associated with any of the outcomes we assessed. CONCLUSIONS: Efforts to improve household food security are important as a means of promoting maternal nutritional status; however, additional research is needed to better understand the role of other factors that are driving the burden of child undernutrition in Cambodia. PMID- 25117994 TI - Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion. AB - Vitamin B12 (cyancobalamin, Cbl) has two active co-enzyme forms, methylcobalamin (MeCbl) and adenosylcobalamin (AdCbl). There has been a paradigm shift in the treatment of vitamin B12 deficiency such that MeCbl is being extensively used and promoted. This is despite the fact that both MeCbl and AdCbl are essential and have distinct metabolic fates and functions. MeCbl is primarily involved along with folate in hematopiesis and development of the brain during childhood. Whereas deficiency of AdCbl disturbs the carbohydrate, fat and amino-acid metabolism, and hence interferes with the formation of myelin. Thereby, it is important to treat vitamin B12 deficiency with a combination of MeCbl and AdCbl or hydroxocobalamin or Cbl. Regarding the route, it has been proved that the oral route is comparable to the intramuscular route for rectifying vitamin B12 deficiency. PMID- 25117995 TI - Body composition analysis in older adults with dementia. Anthropometry and bioelectrical impedance analysis: a critical review. AB - In clinical practice, geriatric nutritional assessment usually includes nutritional screening, a simple anthropometric assessment, measurement of various biochemical parameters, such as serum albumin, and sometimes (not always) body composition analysis (BCA). However, there is a high prevalence of undiagnosed malnutrition in patients with dementia. Several factors contribute to this situation; probably, the most notable is the methodology used to assess body composition (BC). In this regard, for BCA, techniques are needed that are noninvasive, affordable, safe, simple and that require the minimum possible collaboration by the elderly patient. Consequently, body mass index (BMI) and waist circumference (WC) are widely used as indicators of overall and central adiposity, respectively; however, there is no consensus on the cutoffs for the elderly, and changes in BC (especially muscle-mass depletion) are masked by normal values of BMI and WC. Bioimpedance analysis is a simple, cost-effective and precise method for BCA, provided that cross-validated equations are used. Its main disadvantage is that it is highly sensitive to changes in body water (overhydration or dehydration), leading to substantial errors in BC estimates. However, using Bioelectrical Impedance Vector Analysis errors are minimized, as there is no need for the subject to be normally hydrated and it does not require the use of predictive models. PMID- 25117996 TI - Winter 25-hydroxyvitamin D levels in young urban adults are affected by smoking, body mass index and educational level. AB - BACKGROUND/OBJECTIVES: To study the relationship of winter 25 hydroxycholecalciferol (25-OHD) levels with age, education, place of residency, marital status and body mass index (BMI) as they may affect sun exposure, vitamin D synthesis and metabolism. SUBJECTS/METHODS: Subjects (1952) answered a structured questionnaire concerning education, marital status and smoking; and body weight/height, and parathyroid hormone and 25-OHD were measured. RESULTS: 25 OHD levels were higher in the males with elementary and secondary education compared with higher education (46.8+/-18.5 and 43.7+/-16 vs 39.9+/-15.3 nmol/l, P<0.01). Vitamin D deficiency was more prevalent (16.7%, (13.1-20.2) vs 10.8%, (8.4-13.2), P=0.08) and sufficiency was less prevalent (24.6% (20-29.2) vs 33.7%, (29.5-37.8), P=0.005) in those with higher than secondary education. No differences were found among the females. Male smokers had lower 25-OHD than nonsmokers (40.2+/-16.6 vs 43.6+/-15.7 nmol/l, P=0.004). Deficiency was more prevalent in the male smokers than nonsmokers with secondary and higher education (secondary 16.6%, (10.1-22.4) vs 8.2%, (5.1-11.3), P=0.006; higher 27.4%, (17.7 37.1) vs 13.2%, (9.0-17.5), P=0.003). 25-OHD was lower in the obese than in the normal-weight females (34.6+/-16.2 vs 38.2+/-17.8 nmol/l, analysis of variance, P=0.014), but not males. Marital status was not related to 25-OHD. Only in the urban residents, increasing BMI in the young females increased the risk for vitamin D deficiency by 1%, and smoking had an odds ratio of 1.99 (1.05-3.78) in the young and 2.5 (1.07-5.75) in the middle-aged males. CONCLUSIONS: Smoking and higher education in the males and obesity in the females were factors for vitamin D deficiency among Bulgarian urban population. PMID- 25117997 TI - Bioavailability of vitamin D2 from enriched mushrooms in prediabetic adults: a randomized controlled trial. AB - BACKGROUND/OBJECTIVES: Based on the growing evidence of risk reduction from fresh fruit and vegetable consumption and an inverse relationship between serum 25 hydroxyvitamin D (25OHD) and the risk of type 2 diabetes (T2D), we determined the benefits of regularly consuming vitamin D-enriched mushrooms in a prediabetic cohort. Exposing edible mushrooms to ultraviolet B (UVB) light increases vitamin D2 (D2) and raises serum 25OHD2 in healthy young adults; however, their benefit to deficient prediabetics and glucose metabolism remains untested. SUBJECTS/METHODS: Forty-three prediabetic, D-deficient adults (25OHD<=20 ng/ml), BMI>25 were randomized to four groups consuming daily entrees containing 100 g fresh sliced cooked mushrooms prepared by a chef for 16 weeks. Two groups were fed UVB-treated mushrooms initially containing: 600 IU D2 or 4000 IU D2; each one also received one capsule of placebo daily. Two control groups were fed untreated mushrooms and D3 dietary supplements at two label doses: 600 IU D3 and 4000 IU D3. D2 and D3 content were analyzed in mushrooms, before and after cooking and in over-the-counter supplements. RESULTS: After 16 weeks, both D2-UVB-mushroom entree doses, which were significantly lower after cooking, produced modest or no increases in 25OHD2 or total 25OHD relative to the positive control subjects who actually consumed about 1242 and 7320 IU per day of D3 (higher than stated on the label). CONCLUSIONS: Unanticipated D2 cooking loss from fresh UVB mushrooms and probable low absorption and/or hydroxylation may explain the smaller increase in 25OHD2 in our prediabetic overweight/obese cohort compared with past findings in younger, healthy subjects. Moreover, no dose or vitamin D source was associated with modifying T2D risk factors. PMID- 25117998 TI - Associations of sugar-containing beverages with asthma prevalence in 11-year-old children: the PIAMA birth cohort. AB - BACKGROUND/OBJECTIVES: Recently, a few studies have linked soft drink consumption to increased asthma risk, but the contribution of different types of soft drinks is unknown. We investigated cross-sectional associations between six different types of soft drinks and asthma in 11-year-old children. SUBJECTS/METHODS: We analyzed data of 2406 children participating in the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort. At age 11, children self reported consumption of sugar-added drinks, diet drinks, sweetened milk drinks, 100% fruit juice, energy drinks and sport drinks. The definition of asthma was based on parental reports of wheezing, prescription of inhaled corticosteroids and doctor's diagnosis of asthma. RESULTS: The prevalence of asthma in this study was 5.8%. In adjusted logistic regression analyses, asthma risk was increased for high (?10 glasses/week (gl/wk) versus low (<4 gl/wk) consumption of 100% fruit juice (odds ratio (OR): 2.09, 95% confidence interval (CI): 1.21-3.60), sugar added drinks (OR: 1.56, 95%CI: 0.95-2.56) and for very high (>21.5 gl/wk) versus low (<12.5 gl/wk) total sugar-containing beverage (SCB) consumption (OR: 1.91, 95%CI: 1.04-3.48). Consumption of other beverages and consumption of fruit were not associated with increased asthma risk. No evidence for mediation of the observed associations by body mass index was found. CONCLUSIONS: This study indicates that high consumption of 100% fruit juice and total SCBs is associated with increased asthma risk in children. The positive association between consumption of 100% fruit juice and asthma is an unexpected finding that needs confirmation in future studies. PMID- 25117999 TI - Omega-3 supplementation during the first 5 years of life and later academic performance: a randomised controlled trial. AB - BACKGROUND/OBJECTIVES: Consumption of oily fish more than once per week has been shown to improve cognitive outcomes in children. However, it is unknown whether similar benefits can be achieved by long-term omega-3 fatty acid supplementation. The objective was to investigate the effect of omega-3 fatty acid supplementation during the first 5 years of life on subsequent academic performance in children by conducting a secondary analysis of the CAPS (Childhood Asthma Prevention Study). SUBJECTS/METHODS: A total of 616 infants with a family history of asthma were randomised to receive tuna fish oil (high in long-chain omega-3 fatty acids, active) or Sunola oil (low in omega-3 fatty acids, control) from the time breastfeeding ceased or at the age of 6 months until the age of 5 years. Academic performance was measured by a nationally standardised assessment of literacy and numeracy (National Assessment Program Literacy and Numeracy (NAPLAN)) in school years 3, 5, 7 and 9. Plasma omega-3 fatty acid levels were measured at regular intervals until 8 years of age. Between-group differences in test scores, adjusted for maternal age, birth weight and maternal education, were estimated using mixed-model regression. RESULTS: Among 239 children, there were no significant differences in NAPLAN scores between active and control groups. However, at 8 years, the proportion of omega-3 fatty acid in plasma was positively associated with the NAPLAN score (0.13 s.d. unit increase in score per 1% absolute increase in plasma omega-3 fatty acid (95% CI 0.03, 0.23)). CONCLUSIONS: Our findings do not support the practice of supplementing omega-3 fatty acids in the diet of young children to improve academic outcomes. Further exploration is needed to understand the association between plasma omega-3 fatty acid levels at 8 years and academic performance. PMID- 25118001 TI - Prenatal diagnosis of 24 cases of microduplication 22q11.2: an investigation of phenotype-genotype correlations. AB - OBJECTIVE: Microduplication 22q11.2 is primarily characterized by a highly variable clinical phenotype, which ranges from apparently normal or slightly dysmorphic features (in the presence or absence of learning disorders) to severe malformations with profound mental retardation. Hence, genetic counseling is particularly challenging when microduplication 22q11.2 is identified in a prenatal diagnosis. Here, we report on 24 prenatal cases of microduplication 22q11.2. METHODS: Seventeen of the cases were also reanalyzed by microarray analysis, in order to determine copy number variations (CNVs, which are thought to influence expressivity). We also searched for possible correlations between fetal phenotypes, indications for invasive prenatal diagnosis, inheritance, and pregnancy outcomes. RESULTS: Of the 24 cases, 15 were inherited, six occurred de novo, and three were of unknown origin. Termination of pregnancy occurred in seven cases and was mainly decided on the basis of ultrasound findings. Moreover, additional CNVs were found in some patients and we try to make a genotype phenotype correlation. CONCLUSION: We discuss the complexity of genetic counseling for microduplication 22q11.2 and comment on possible explanations for the clinical heterogeneity of this syndrome. In particular, we assessed the co existence of additional CNVs and their contribution to phenotypic variations in chromosome 22q11.2 microduplication syndrome. PMID- 25118000 TI - Lung function, 25-hydroxyvitamin D concentrations and mortality in US adults. AB - OBJECTIVE: To explore the associations between serum concentrations of vitamin D (25(OH)D) and all-cause mortality among US adults defined by lung function (LF) status, particularly among adults with obstructive LF (OLF). METHODS: Data from 10,795 adults aged 20-79 years (685 with restrictive LF (RLF) and 1309 with OLF) who participated in the Third National Health and Nutrition Examination Survey (1988-1994), had a spirometric examination, and were followed through 2006 were included. RESULTS: During 14.2 years of follow-up, 1792 participants died. Mean adjusted concentrations of 25(OH)D were 75.0 nmol/l (s.e. 0.7) for adults with normal LF (NLF), 70.4 nmol/l (s.e. 1.8) for adults with RLF, 75.5 nmol/l (s.e. 1.5) for adults with mild obstruction and 71.0 nmol/l (s.e. 1.9) among adults with moderate or worse obstruction (P=0.030). After adjustment for sociodemographic factors, lifestyle factors, clinical variables and prevalent chronic conditions, a concentration of <25 nmol/l compared with ? 75 nmol//l was associated with mortality only among adults with NLF (hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.03, 3.00). Among participants with OLF, adjusted HRs were 0.65 (95% CI 0.29, 1.48), 1.21 (95% CI 0.89, 1.66) and 0.97 (95% CI 0.78, 1.19) among those with concentrations <25, 25-<50 and 50-<75 nmol/l, respectively. CONCLUSIONS: Baseline concentrations of 25(OH)D did not significantly predict mortality among US adults with impaired LF. PMID- 25118002 TI - Efficacy of silver-loaded nanofiber dressings in Candida albicans-contaminated full-skin thickness rat burn wounds. AB - In this experimental study, the effects of nanofiber dressings containing different forms of silver on full-thickness rat burn contaminated with Candida albicans was analyzed. A full-thickness skin burn was formed on a total of 32 Sprague-Dawley rats. After the burn wound was seeded with a 10 colony-forming units/ml standard strain of Candida albicans ATCC90028, the animals were divided into four groups. The effects of topical silver sulfadiazine and two recently designed nanofiber dressings containing nanosilver and silversulfadiazine as active materials were compared with the control group. There was a significant difference in the Candida growth on the burn eschar tissue among the groups. The difference for Candida growth in the burn eschar between the control group and the 1% silver sulfadiazine-containing nanofiber dressing group was statistically significant (P< 0.01). Silver sulfadiazine-containing nanofiber dressing was the most effective agent in the treatment of Candida albicans-contaminated burn wounds. Because of their regenerative potential, silver-loaded nanofiber dressings could be a good alternative for infected burn wounds. PMID- 25118003 TI - Using latent class analysis to develop a model of the relationship between socioeconomic position and ethnicity: cross-sectional analyses from a multi ethnic birth cohort study. AB - BACKGROUND: Almost all studies in health research control or investigate socioeconomic position (SEP) as exposure or confounder. Different measures of SEP capture different aspects of the underlying construct, so efficient methodologies to combine them are needed. SEP and ethnicity are strongly associated, however not all measures of SEP may be appropriate for all ethnic groups. METHODS: We used latent class analysis (LCA) to define subgroups of women with similar SEP profiles using 19 measures of SEP. Data from 11,326 women were used, from eight different ethnic groups but with the majority from White British (40%) or Pakistani (45%) backgrounds, who were recruited during pregnancy to the Born in Bradford birth cohort study. RESULTS: Five distinct SEP subclasses were identified in the LCA: (i) "Least socioeconomically deprived and most educated" (20%); (ii) "Employed and not materially deprived" (19%); (iii) "Employed and no access to money" (16%); (iv) "Benefits and not materially deprived" (29%) and (v) "Most economically deprived" (16%). Based on the magnitude of the point estimates, the strongest associations were that compared to White British women, Pakistani and Bangladeshi women were more likely to belong to groups: (iv) "benefits and not materially deprived" (relative risk ratio (95% CI): 5.24 (4.44, 6.19) and 3.44 (2.37, 5.00), respectively) or (v) most deprived group (2.36 (1.96, 2.84) and 3.35 (2.21, 5.06) respectively) compared to the least deprived class. White Other women were more than twice as likely to be in the (iv) "benefits and not materially deprived group" compared to White British women and all ethnic groups, other than the Mixed group, were less likely to be in the (iii) "employed and not materially deprived" group than White British women. CONCLUSIONS: LCA allows different aspects of an individual's SEP to be considered in one multidimensional indicator, which can then be integrated in epidemiological analyses. Ethnicity is strongly associated with these identified subgroups. Findings from this study suggest a careful use of SEP measures in health research, especially when looking at different ethnic groups. Further replication of these findings is needed in other populations. PMID- 25118005 TI - Biological Activities of Plant Pigments Betalains. AB - Betalains are a family of natural pigments present in most plants of the order Caryophyllales. They provide colors ranging from yellow to violet to structures that in other plants are colored by anthocyanins. These include not only edible fruits and roots but also flowers, stems, and bracts. The recent characterization of different bioactivities in experiments with betalain containing extracts and purified pigments has renewed the interest of the research community in these molecules used by the food industry as natural colorants. Studies with multiple cancer cell lines have demonstrated a high chemopreventive potential that finds in vitro support in a strong antiradical and antioxidant activity. Experiments in vivo with model animals and bioavailability studies reinforce the possible role played by betalains in the diet. This work provides a critical review of all the claimed biological activities of betalains, showing that the bioactivities described might be supported by the high antiradical capacity of their structural unit, betalamic acid. Although more investigations with purified compounds are needed, the current evidences suggest a strong health-promoting potential. PMID- 25118004 TI - Provision of KEL1-negative blood to obstetric patients: a 3-year single institution retrospective review. AB - BACKGROUND: KEL1 alloimmunization is a major cause of hemolytic disease of the fetus and newborn (HDFN). While select countries have guidelines for preventing transfusion-associated KEL1 alloimmunization, the United States does not. Beth Israel Deaconess Medical Center instituted a policy in April 2009 whereby women not more than 50 years of age on the obstetric service were transfused KEL1 negative red blood cells (RBCs). We sought to determine compliance and impact for prevention of KEL1 alloimmunization and HDFN. STUDY DESIGN AND METHODS: All women not more than 50 years of age without anti-K transfused RBCs during an obstetric admission from April 9, 2009, to April 9, 2012, were identified (227). Adherence to policy, factors contributing to nonadherence, and subsequent impact were evaluated. For comparison, all cases of anti-K detection in women not more than 50 years of age admitted to nonobstetric services and all cases of transfusion associated KEL1 alloimmunization in women not more than 50 years of age during the 10 years prior were identified. RESULTS: Eighty-four percent received only KEL1-negative units. Three (1.3%) women not more than 50 years of age on the obstetric service were identified with anti-K, while 17 (1.5%) women not more than 50 years of age on nonobstetric services had anti-K detected; only five of 20 had a prior RBC transfusion. In the 10 years prior, there were 27 cases of transfusion-associated KEL1 alloimmunization in women not more than 50 years of age. There were no cases of KEL1 HDFN in either period. CONCLUSION: Although the findings demonstrate feasibility of providing KEL1-negative RBCs to women of childbearing potential, evidence for clinical benefit is lacking. The low prevalence of KEL1 in blood donors, the lack of significant differences in alloimmunization rates, and no cases of HDFN during the study period questions the clinical benefit of such a policy. PMID- 25118006 TI - The rehabilitation role in chronic kidney and end stage renal disease. AB - Chronic kidney disease (CKD) worldwide is rising markedly becoming a priority public health problem. The progression of CKD cause functional limitation and severe disability with poor quality of life. The aim of present review was to highlight the effect of rehabilitation in CKD and ESRD subjects. The rehabilitative process is unique in treating disabled people according to a holistic approach with the aim of supporting a person's independent living and autonomy. CKD are associated with an increased risk of functional impairment, independent of age, gender, and co-morbidities. Clinicians should counsel patients with CKD including frail elder people to increase physical activity levels and target that regular physical activity including aerobic or endurance exercises training benefits health. In old subjects with CKD and multiple functional impairments, the traditional disease based model should be changed to individualized patient-centered approach that prioritizes patient preferences. Patients receiving haemodialysis have a considerably lower exercise tolerance, functional capacity, and more muscle wasting than healthy subjects or patients with less severe CKD. Exercise training or comprehensive multi-dimensional strategy and goal-oriented intervention should be also provided in ESRD older subjects. Structured prevention programs based on reducing the risk factors for CKD and rehabilitative strategies could reduce disability occurrence. PMID- 25118007 TI - Familial co-segregation of Coffin-Lowry syndrome inherited from the mother and autosomal dominant Waardenburg type IV syndrome due to deletion of EDNRB inherited from the father. AB - We report an African-American family that was identified after the proposita was referred for diagnostic evaluation at 41/2 months with a history of Hirschsprung and dysmorphic features typical of Waardenburg syndrome (WS). Family evaluation revealed that the father had heterochromidia irides and hypertelorism supporting the clinical diagnosis of WS; however, examination of the mother revealed characteristic facial and digital features of Coffin-Lowry syndrome (CLS). Molecular testing of the mother identified a novel 2 bp deletion (c.865_866delCA) in codon 289 of RPS6KA3 leading to a frame-shift and premature termination of translation 5 codons downstream (NM_004586.2:p.Gln289ValfsX5). This deletion also was identified in the proposita and her three sisters with a clinical suspicion of CLS, all of whom as carriers for this X-linked disorder had very subtle manifestations. The molecular confirmation of WS type 4 (Shah-Waardenburg; WS4) was not as straightforward. To evaluate WS types 1-4, multiple sequential molecular tests were requested, including Sanger sequencing of all exons, and deletion/duplication analysis using MLPA for PAX3, MITF, SOX10, EDN3 and EDNRB. Although sequencing did not identify any disease causing variants, MLPA identified a heterozygous deletion of the entire EDNRB in the father. This deletion was also found in the proposita and the oldest child. Since the heterozygous deletion was the only change identified in EDNRB, this family represents one of the few cases of an autosomal dominant inheritance of WS4 involving the endothelin pathway. Altogether, clinical evaluation of the family revealed one child to be positive for WS4 and two positive for CLS, while two children were positive for both diseases simultaneously (including the proposita) while another pair test negative for either disease. This kinship is an example of the coincidence of two conditions co-segregating in one family, with variable phenotypes requiring molecular testing to confirm the clinical diagnoses. PMID- 25118008 TI - NKX2.5 mutation identification on exome sequencing in a patient with heterotaxy. AB - Exome sequencing enables us to screen most of the protein coding genes in an unbiased way, this technique represents an ideal tool to identify previously under- or unappreciated phenotypes associated with known disease genes and genetic disorders. Here we present an illustrative case that required exome sequencing to identify a genetic alteration associated with the clinical features. The phenotype of the proband included heterotaxy, double outlet right ventricle, common atrioventricular canal, total anomalous pulmonary venous connection, asplenia, failure to thrive and short stature. Exome sequencing demonstrated a frameshift mutation c.397_400del (p.P133GfsTer 42) in NKX2.5. Although a single previous case of heterotaxy was reported in a large familial case of NKX2.5, heterotaxy is not clinically appreciated to be a part of the phenotypic spectrum associated with NKX2.5 mutations. This case report demonstrates the utility of exome sequencing in expanding a phenotypic spectrum of a known Mendelian disorder. We predict that this type of unexpected identification of mutations in known-disease associated genes in patients with atypical or expanded phenotypes will occur with increasing frequency as the use of exome and genome sequencing become more common tools in diagnosing patients with syndromic and non-syndromic foms of structural birth defects. PMID- 25118009 TI - Modelling the effects of cochlear implant current focusing. AB - OBJECTIVES: A finite element model of the human coiled cochlea was used to model the voltage distribution due to stimulation by the individual electrodes of a cochlear implant. The scalar position of the electrode array was also varied in order to investigate its effect on the voltage distribution. Multi-electrode current focusing methods were then investigated, with the aim of increasing spatial selectivity. METHODS: Simultaneous current focusing is initially achieved, as in previous publications, by calculating the input currents to the 22 electrodes that best separates the voltages at these electrode positions. The benefits of this electrode focusing strategy do not, however, entirely carry over to the predicted voltage distributions at the position of the spiral ganglion cells, where excitation is believed to occur. A novel focusing strategy is then simulated, which compensates for the impedances between the currents at the electrode sites and the voltage distribution directly at the position of the spiral ganglion cells. RESULTS: The new strategy produces much better focusing at the sites of the spiral ganglion cells, as expected, but at the cost of increased current requirements. Regularization was introduced in order to reduce current requirements, which also reduced the sensitivity of the solution to uncertainties in the impedance matrix, so that improved focusing was achieved with similar current requirements to that of electrode focusing. DISCUSSION: Although such focusing strategies cannot be achieved in practice at the moment, since the responses from the electrodes to the neural sites cannot be determined with currently available recording methods, these results do support the feasibility of a more effective focusing strategy, which may provide improved spectral resolution leading to improved perception of sound. PMID- 25118010 TI - Occurrence and expression of bacterial human virulence gene homologues in natural soil bacteria. AB - The presence and in vitro expression of homologues to 22 bacterial human virulence determinants amongst culturable soil bacteria were investigated. About 25% of the bacterial isolates contained virulence gene homologues representing toxin (hblA, cytK2), adhesin (fimH), regulator (phoQ) and resistance (yfbI) determinants in pathogenic bacteria. The homologues of the toxin genes were found in Actinobacteria and Firmicutes (hblA), and in Firmicutes and Alpha- and Gammaproteobacteria (cytK2). The homologues to the type 1 fimbrial adhesin gene, fimH, and the L-Ara4N transferase gene, yfbI, were observed in Actinobacteria, Firmicutes and Gammaproteobacteria. The regulator gene, phoQ, was only found in Gammaproteobacteria. The presence of cytK2 in Alpha- and Gammaproteobacteria, fimH in Actinobacteria and Firmicutes, and hblA in Actinobacteria has not previously been described. A close sequence similarity (84-100%) was observed between the genes of environmental and clinical isolates, and expression assays suggested that the genes in some cases were expressed in vitro. The presence of functional virulence gene homologues underpins their importance for the survival of environmental bacteria. Furthermore, the high degree of sequence conservation to clinical sequences indicates that natural environments may be 'evolutionary cribs' of emerging pathogens. PMID- 25118017 TI - Genetic and environmental contributions to social anxiety across different ages: a meta-analytic approach to twin data. AB - Social anxiety disorder (SAD) and social anxiety symptoms (SAS) have been largely studied both epidemiologically and genetically, however, estimates of genetic and environmental influences for these phenotypes widely vary across reports. Based upon available literature, 13 cohorts (42,585 subjects) were included in 3 meta analytic estimates of the standardized variance components of aetiological influences on SAD/SAS, on the effect of age and of phenotype (symptoms vs. diagnosis). The proportions of variance accounted for by genetic and environmental factors were calculated by averaging estimates among studies, and pondered by the number of individuals in each sample. Meta-analytic estimations showed that genetic and non-shared environmental factors explain most of individual differences for SAD/SAS. In adults, the genetic contribution was half than that in younger patients, with higher contribution of non-shared environmental influences. In contrast, the shared environmental factors seem to be less relevant. PMID- 25118016 TI - Successful treatment of post-transplant thrombocytopenia with romiplostim in a pediatric patient with X-linked chronic granulomatous disease. AB - Thrombocytopenia is a frequent complication following HSCT in pediatric patients. Romiplostim is a TPO receptor agonist that has been utilized successfully in the treatment of pediatric patients with immune thrombocytopenia. We describe a three yr-old male with X-linked CGD treated with an unrelated donor bone marrow transplant. His course was complicated by the development of symptomatic thrombocytopenia. He was started on romiplostim with prompt improvement in his thrombocytopenia. We found the use of romiplostim to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of immunosuppressive agents such as corticosteroids. PMID- 25118019 TI - On the state of scientific English and how to improve it - Part 7: Separating key concepts and qualifications. PMID- 25118018 TI - In vitro anticancer activity of loquat tea by inducing apoptosis in human leukemia cells. AB - Fresh loquat leaves have been used as folk health herb in Asian countries for long time, although the evidence supporting their functions is still minimal. This study aimed to clarify the chemopreventive effect of loquat tea extract (LTE) by investigating the inhibition on proliferation, and underlying mechanisms in human promyelocytic leukemia cells (HL-60). LTE inhibited proliferation of HL 60 in a dose-dependent manner. Molecular data showed that the isolated fraction of LTE induced apoptosis of HL-60 as characterized by DNA fragmentation; activation of caspase-3, -8, and -9; and inactivation of poly(ADP)ribose polymerase. Moreover, LTE fraction increased the ratio of pro-apoptotic Bcl-2 associated X protein (Bax)/anti-apoptotic myeloid cell leukemia 1 (Mcl-1) that caused mitochondrial membrane potential loss and cytochrome c released to cytosol. Thus, our data indicate that LTE might induce apoptosis in HL-60 cells through a mitochondrial dysfunction pathway. These findings enhance our understanding for chemopreventive function of loquat tea. PMID- 25118020 TI - A polymerization chaperone: A novel hypothesis for the +TIP network (comment on DOI 10.1002/bies.201400029). PMID- 25118024 TI - Tectonic gene mutations in patients with Joubert syndrome. AB - So far very few patients with sequence variants in the closely related tectonic genes TCTN1-3 have been described. By multi-gene panel next-generation sequencing (NGS) in patients with Joubert syndrome, we identified two more patients and summarize what is currently known about the phenotypes associated with sequence variants in these genes. In a boy aged 12 years with intellectual disability and the classical molar tooth sign on MRI, a homozygous splice-site sequence variant in TCTN3 leading to in-frame skipping of exon 7 was detected. A previously described non-truncating sequence variant in TCTN3 was also associated with Joubert syndrome, whereas four truncating sequence variants were detected in patients with Meckel-Gruber or Mohr-Majewski syndrome. The second patient, a boy aged 7 years with severe psychomotor retardation, was found to carry a homozygous canonic splice-site sequence variant in TCTN2. So far, only three sequence variants associated with Joubert syndrome and two with Meckel-Gruber syndrome have been described in this gene. Reviewing the clinical data on patients with sequence variants in the tectonic genes TCTN1-3 reveals that all of them have a neurological phenotype with vermis hypoplasia or occipital encephalocele associated with severe intellectual disability in the surviving patients. In contrast, other features frequently seen in patients with ciliopathies such as nephronophthisis, liver fibrosis, retinal dystrophy or coloboma have not been reported. Our patients emphasize the usefulness and efficacy of a comprehensive NGS panel approach. A concise genetic diagnosis may help to prevent unnecessary investigations and improve the clinical management of these patients. PMID- 25118025 TI - VPS35 and DNAJC13 disease-causing variants in essential tremor. AB - Exome-sequencing analyses have identified vacuolar protein sorting 35 homolog (VPS35) and DnaJ (Hsp40) homolog, subfamily C, member 13 (DNAJC13) harboring disease-causing variants for Parkinson disease (PD). Owing to the suggested clinical, pathological and genetic overlap between PD and essential tremor (ET) we assessed the presence of two VPS35 and DNAJC13 disease-causing variants in ET patients. TaqMan probes were used to genotype VPS35 c.1858G>A (p.(D620N)) (rs188286943) and DNAJC13 c.2564A>G (p.(N855S)) (rs387907571) in 571 ET patients of European descent, and microsatellite markers were used to define the disease haplotype in variant carriers. Genotyping of DNAJC13 identified two ET patients harboring the c.2564A>G (p.(N855S)) variant previously identified in PD patients. Both patients appear to share the disease haplotype previously reported. ET patients with the VPS35 c.1858G>A (p.(D620N)) variants were not observed. Although a genetic link between PD and ET has been suggested, DNAJC13 c.2564A>G (p.(N855S)) represents the first disease-causing variant identified in both, and suggests the regulation of clathrin dynamics and endosomal trafficking in the pathophysiology of a subset of ET patients. PMID- 25118026 TI - Regions of homozygosity identified by oligonucleotide SNP arrays: evaluating the incidence and clinical utility. AB - Copy neutral segments with allelic homozygosity, also known as regions of homozygosity (ROHs), are frequently identified in cases interrogated by oligonucleotide single-nucleotide polymorphism (oligo-SNP) microarrays. Presence of ROHs may be because of parental relatedness, chromosomal recombination or rearrangements and provides important clues regarding ancestral homozygosity, consanguinity or uniparental disomy. In this study of 14 574 consecutive cases, 832 (6%) were found to harbor one or more ROHs over 10 Mb, of which 651 cases (78%) had multiple ROHs, likely because of identity by descent (IBD), and 181 cases (22%) with ROHs involving a single chromosome. Parental relatedness was predicted to be first degree or closer in 5%, second in 9% and third in 19%. Of the 181 cases, 19 had ROHs for a whole chromosome revealing uniparental isodisomy (isoUPD). In all, 25 cases had significant ROHs involving a single chromosome; 5 cases were molecularly confirmed to have a mixed iso- and heteroUPD15 and 1 case each with segmental UPD9pat and segmental UPD22mat; 17 cases were suspected to have a mixed iso- and heteroUPD including 2 cases with small supernumerary marker and 2 cases with mosaic trisomy. For chromosome 15, 12 (92%) of 13 molecularly studied cases had either Prader-Willi or Angelman syndrome. Autosomal recessive disorders were confirmed in seven of nine cases from eight families because of the finding of suspected gene within a ROH. This study demonstrates that ROHs are much more frequent than previously recognized and often reflect parental relatedness, ascertain autosomal recessive diseases or unravel UPD in many cases. PMID- 25118027 TI - The phenotype of congenital insensitivity to pain due to the NaV1.9 variant p.L811P. PMID- 25118028 TI - Malan syndrome: Sotos-like overgrowth with de novo NFIX sequence variants and deletions in six new patients and a review of the literature. AB - De novo monoallelic variants in NFIX cause two distinct syndromes. Whole gene deletions, nonsense variants and missense variants affecting the DNA-binding domain have been seen in association with a Sotos-like phenotype that we propose is referred to as Malan syndrome. Frameshift and splice-site variants thought to avoid nonsense-mediated RNA decay have been seen in Marshall-Smith syndrome. We report six additional patients with Malan syndrome and de novo NFIX deletions or sequence variants and review the 20 patients now reported. The phenotype is characterised by moderate postnatal overgrowth and macrocephaly. Median height and head circumference in childhood are 2.0 and 2.3 standard deviations (SD) above the mean, respectively. There is overlap of the facial phenotype with NSD1 positive Sotos syndrome in some cases including a prominent forehead, high anterior hairline, downslanting palpebral fissures and prominent chin. Neonatal feeding difficulties and/or hypotonia have been reported in 30% of patients. Developmental delay/learning disability have been reported in all cases and are typically moderate. Ocular phenotypes are common, including strabismus (65%), nystagmus (25% ) and optic disc pallor/hypoplasia (25%). Other recurrent features include pectus excavatum (40%) and scoliosis (25%). Eight reported patients have a deletion also encompassing CACNA1A, haploinsufficiency of which causes episodic ataxia type 2 or familial hemiplegic migraine. One previous case had episodic ataxia and one case we report has had cyclical vomiting responsive to pizotifen. In individuals with this contiguous gene deletion syndrome, awareness of possible later neurological manifestations is important, although their penetrance is not yet clear. PMID- 25118029 TI - Characterization of the first intragenic SATB2 duplication in a girl with intellectual disability, nearly absent speech and suspected hypodontia. AB - SATB2, a gene encoding a highly conserved DNA-binding protein, is known to have an important role in craniofacial and neuronal development. Only a few patients with SATB2 variants have been described so far. Recently, Docker et al provided a summary of these patients and delineated the SAS (SATB2-associated syndrome). We here report on a girl with intellectual disability, nearly absent speech and suspected hypodontia who was shown to carry an intragenic SATB2 tandem duplication hypothesized to lead to haploinsufficiency of SATB2. Preliminary information on this patient had already been included in the article by Docker et al. We want to give a detailed description of the patient's phenotype and genotype, providing further insight into the spectrum of the molecular mechanisms leading to SAS. PMID- 25118031 TI - Short-term trained lexical categories produce preattentive categorical perception of color: evidence from ERPs. AB - The present study investigated whether short-term trained lexical categories could produce lateralized preattentive categorical perception (CP) of color. Participants' event-related potentials were recorded while performing a visual oddball task in which standard and deviant colored stimuli from the same or different novel lexical categories were presented. Two groups of participants were recruited: a group trained on these novel categories (n = 26), and an untrained control group (n = 26). Results of paired t tests showed that deviants did not evoke significant visual mismatch negativity, with the exception of deviants from different novel categories presented in the right visual field of the training group. This suggests that short-term trained lexical categories produce lateralized preattentive color CP, and language enhances sensitivity to the differences among between-category stimuli. PMID- 25118030 TI - Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the classification. AB - Dentinogenesis imperfecta is an autosomal dominant disease characterized by severe hypomineralization of dentin and altered dentin structure. Dentin extra cellular matrix is composed of 90% of collagen type I and 10% of non-collagenous proteins among which dentin sialoprotein (DSP), dentin glycoprotein (DGP) and dentin phosphoprotein (DPP) are crucial in dentinogenesis. These proteins are encoded by a single gene: dentin sialophosphoprotein (DSPP) and undergo several post-translational modifications such as glycosylation and phosphorylation to contribute and to control mineralization. Human mutations of this DSPP gene are responsible for three isolated dentinal diseases classified by Shield in 1973: type II and III dentinogenesis imperfecta and type II dentin dysplasia. Shield classification was based on clinical phenotypes observed in patient. Genetics results show now that these three diseases are a severity variation of the same pathology. So this review aims to revise and to propose a new classification of the isolated forms of DI to simplify diagnosis for practitioners. PMID- 25118034 TI - A missed opportunity? Recognizing pregnancy-associated cardiovascular risk factors. PMID- 25118032 TI - Iodine nutritional status after the implementation of the new iodized salt concentration standard in Zhejiang Province, China. AB - BACKGROUND: Iodine deficiencies were prevalent in China until the introduction of universal salt iodization (USI) in 1995. In 2012, the standard salt iodine concentration was adjusted to 20-30 mg/kg. The success of USI for the control of iodine deficiency disorders requires monitoring its effect at a population level. METHODS: Two cross sectional surveys of a representative sample of children aged 8-10 years in Zhejiang Province were carried out in 2011 and 2013. Data on participants' socio-demographic characteristics were collected from the children using a structured questionnaire. Spot urine samples were collected and delivered to local Center for Disease Control and Prevention laboratory for measuring urinary iodine concentration. In 2011, out of 420 selected children aged 8-10 years, 391 were recorded and provided urine samples. In 2013, out of 1560 selected children aged 8-10 years, 1556 were recorded and provided urine samples. RESULTS: The median urinary iodine concentration of subjects in the 2013 survey was 174.3 MUg/L, significantly lower than that of 2011(p = 0.000). The median urinary iodine concentration of subjects living in urban and rural areas in the 2013 survey was 169.0 MUg/L, and 186.1 MUg/L respectively, significantly lower than that of 2011 only for subjects living in urban areas (p = 0.000). There were no significant differences for subjects living in rural areas in the survey in 2011 and in 2013 (p = 0.086). CONCLUSIONS: At the time the new local iodization policy put forward, iodine nutrition was generally adequate in both urban and rural areas, suggesting that the new policy for adjusting the standard salt iodine concentration is effective. Our data also indicate that the reason people living in urban areas had a lower urinary iodine concentration than people in rural areas may be due to their preference for using non-iodized salt in the last 2 or 3 years. Maintaining USI at an appropriate level is an important part of preventing iodine deficiency disorders and should always be based on regular monitoring and comparison of urinary iodine concentration by province. PMID- 25118035 TI - 20 things you didn't know about women and heart disease. PMID- 25118037 TI - A "nephrological" approach to physical activity. AB - Despite consensus among nephrologists that exercise is important and probably beneficial for their patients, assessment of physical function or encouragement of physical activity is not a part of the routine management of patients with CKD. In order to plan an useful strategy for exercise training we need to clearly define some questions. First of all, nephrologists need to be aware of physical exercise benefits; lack of motivation and increased perceived risk by health care professionals have been identified as contributing factors to physical inactivity. Moreover, the main elements necessary for sustaining exercise programs in this population have to take in account, such as the requirement of exercise professionals, equipment and space, individual prescription, adequate commitment from dialysis and medical staff. When PA may not be implemented, a comprehensive, individualized occupational therapy program may improve functional independence and activity of daily living. Finally, physical function has to be careful monitored and assesses by medical staff. PMID- 25118036 TI - Long-term reproducible expression in human fetal liver hematopoietic stem cells with a UCOE-based lentiviral vector. AB - Hematopoietic Stem Cell (HSC) targeted gene transfer is an attractive treatment option for a number of hematopoietic disorders caused by single gene defects. However, extensive methylation of promoter sequences results in silencing of therapeutic gene expression. The choice of an appropriate promoter is therefore crucial for reproducible, stable and long-term transgene expression in clinical gene therapy. Recent studies suggest efficient and stable expression of transgenes from the ubiquitous chromatin opening element (UCOE) derived from the human HNRPA2B1-CBX3 locus can be achieved in murine HSC. Here, we compared the use of HNRPA2B1-CBX3 UCOE (A2UCOE)-mediated transgene regulation to two other frequently used promoters namely EF1alpha and PGK in human fetal liver-derived HSC (hflHSC). Efficient transduction of hflHSC with a lentiviral vector containing an HNRPA2B1-CBX3 UCOE-eGFP (A2UCOE-eGFP) cassette was achieved at higher levels than that obtained with umbilical cord blood derived HSC (3.1x; p<0.001). While hflHSC were readily transduced with all three test vectors (A2UCOE-eGFP, PGK-eGFP and EF1alpha-eGFP), only the A2-UCOE construct demonstrated sustained transgene expression in vitro over 24 days (p<0.001). In contrast, within 10 days in culture a rapid decline in transgene expression in both PGK-eGFP and EF1alpha-eGFP transduced hflHSC was seen. Subsequently, injection of transduced cells into immunodeficient mice (NOD/SCID/Il2rg-/-) demonstrated sustained eGFP expression for the A2UCOE-eGFP group up to 10 months post transplantation whereas PGK-eGFP and EF1alpha-eGFP transduced hflHSC showed a 5.1 and 22.2 fold reduction respectively over the same time period. We conclude that the A2UCOE allows a more efficient and stable expression in hflHSC to be achieved than either the PGK or EF1alpha promoters and at lower vector copy number per cell. PMID- 25118038 TI - Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation. AB - Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts. BIOLOGICAL SIGNIFICANCE: In this study, a label-free LC-MS was performed to analyze the secretomes of two paired primary fibroblasts, which were isolated from fresh surgical specimen of colorectal adenocarcinoma and adjacent normal colonic tissues and exhibited negative modulatory activity for colon cancer cell growth in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related protein 1 was further revealed to be one of the stroma-derived factors of potential suppression role for colon cancer cell proliferation. Our results provide novel insights into the molecular signatures and the modulatory role of colon cancer associated fibroblasts, and establish a valuable resource for the development of therapeutic agents or novel clinic biomarker. PMID- 25118040 TI - How much is it going to cost me? Bidirectional relations between adolescents' moral personality and prosocial behavior. AB - The current study examined bidirectional relations between adolescents' moral personality (prosocial values, self-regulation, and sympathy) and low- and high cost prosocial behavior toward strangers. Participants included 682 adolescents (M age of child = 14.31, SD = 1.07, 50% female) who participated at two time points, approximately one year apart. Cross-lag analyses suggested that adolescents' values were associated with both low- and high-cost prosocial behavior one year later, self-regulation was associated with high-cost prosocial behavior, and sympathy was associated with low-cost prosocial behavior. Findings also suggested that low-cost prosocial behavior was associated with sympathy one year later, and high-cost prosocial behavior was associated with values. Discussion focuses on reciprocal relations between moral personality and prosocial behavior, and the need to consider a more multidimensional approach to prosocial development during adolescence. PMID- 25118039 TI - Increased methylation of the MOR gene proximal promoter in primary sensory neurons plays a crucial role in the decreased analgesic effect of opioids in neuropathic pain. AB - BACKGROUND: The analgesic potency of opioids is reduced in neuropathic pain. However, the molecular mechanism is not well understood. RESULTS: The present study demonstrated that increased methylation of the Mu opioid receptor (MOR) gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and intraplantar (i.pl.), not intracerebroventricular (i.c.v.) injection of morphine, the potency of morphine analgesia was significantly reduced in nerve-injured mice compared with control sham-operated mice. After peripheral nerve injury, we observed a decreased expression of MOR protein and mRNA, accompanied by an increased methylation status of MOR gene PP, in DRG. However, peripheral nerve injury could not induce a decreased expression of MOR mRNA in the spinal cord. Treatment with 5-aza-2'-deoxycytidine (5-aza-dC), inhibited the increased methylation of MOR gene PP and prevented the decreased expression of MOR in DRG, thereby improved systemic, spinal and periphery morphine analgesia. CONCLUSIONS: Altogether, our results demonstrate that increased methylation of the MOR gene PP in DRG is required for the decreased morphine analgesia in neuropathic pain. PMID- 25118041 TI - Single night video-game use leads to sleep loss and attention deficits in older adolescents. AB - The present study investigated adolescent video-game use prior to bedtime and subsequent sleep, working memory and sustained attention performance. Participants were 21 healthy, good-sleeping adolescents (16 male) aged between 15 and 20 years (M = 17.6 years, SD = 1.8). Time spent video-gaming and subsequent sleep was measured across one night in the sleep laboratory. There were significant correlations between time spent video-gaming and sleep and between video-gaming and sustained attention, but not working memory. Sleep duration, in turn, had a significant negative association with sustained attention performance. Mediation analyses revealed that the relationship between video gaming and sustained attention was fully mediated by sleep duration. These results indicate that video-gaming affected the ability to sustain attention only in as much as it affected sleep. In order to minimise negative consequences of video-game playing, video-games should be used in moderation, avoiding use close to the sleep period, to obviate detriments to sleep and performance. PMID- 25118042 TI - Assessment of 'Fitting to Outcomes Expert' FOXTM with new cochlear implant users in a multi-centre study. AB - OBJECTIVE: To compare the fitting time requirements and the efficiency in achieving improvements in speech perception during the first 6 months after initial stimulation of computer-assisted fitting with the Fitting to Outcome eXpert' (FOX) and a standard clinical fitting procedure. METHOD: Twenty-seven post-lingually deafened adults, newly implanted recipients of the Advanced Bionics HiRes 90KTM cochlear implant from Germany, the UK, and France took part in a controlled, randomized, clinical study. Speech perception was measured for all participants and fitting times were compared across groups programmed using FOX and conventional programming methods. RESULTS: The fitting time for FOX was significantly reduced at 14 days (P < 0.001) but equivalent over the 6-month period. The groups were not well matched for duration of deafness; therefore, speech perception could not be compared across groups. DISCUSSION: Despite including more objective measures of performance than a standard fitting approach and the adjustment of a greater range of parameters during initial fitting, FOX did not add to the overall fitting time when compared to the conventional approach. FOX significantly reduced the fitting time in the first 2 weeks and by providing a standard fitting protocol, reduced variability across centres. CONCLUSIONS: FOX computer-assisted fitting can be successfully used at switch on, in different clinical environments, reducing fitting time in the first 2 weeks and is efficient at providing a usable program. PMID- 25118044 TI - Binding of nucleobases with graphene and carbon nanotube: a review of computational studies. AB - Functionalized carbon nanotubes (CNTs) constitute a new class of nanostructured materials that have vast applications in CNT purification and separation, biosensing, drug delivery, etc. Hybrids formed from the functionalization of CNT with biological molecules have shown interesting properties and have attracted great attention in recent years. Of particular interest is the hybridization of single- or double-stranded nucleic acid (NA) with CNT. Nucleobases, as the building blocks of NA, interact with CNT and contribute strongly to the stability of the NA-CNT hybrids and their properties. In this work, we present a thorough review of previous studies on the binding of nucleobases with graphene and CNT, with a focus on the simulation works that attempted to evaluate the structure and strength of binding. Discrepancies among these works are identified, and factors that might contribute to such discrepancies are discussed. PMID- 25118045 TI - A polymerized ionic liquid-supported B12 catalyst with a ruthenium trisbipyridine photosensitizer for photocatalytic dechlorination in ionic liquids. AB - By immobilizing a B12 complex and a Ru(ii) trisbipyridine photosensitizer in a polymerized ionic liquid (PIL), a visible light-driven photocatalyst was developed. The synthesized copolymer was characterized by GPC and DLS, and using UV-vis absorption spectra and luminescence spectra. The Ru(ii) trisbipyridine photosensitizer in the copolymer showed an enhanced emission compared to that of the monomer in the ionic liquid, 1-butyl-4-methylimidazolium bis(trifluoromethanesulfonyl)amide ([C4mim][NTf2]). Formation of the Co(i) species of the B12 complex in the copolymer was confirmed by the UV-vis spectral change in [C4mim][NTf2] containing a sacrificial reductant (triethanolamine) under irradiation with visible light. The copolymer showed a high photocatalytic activity in various ionic liquids for 1,1-bis(4-chlorophenyl)-2,2,2 trichloroethane (DDT) dechlorination with ~99% conversion after visible light irradiation for 2 h. Furthermore, both the B12 catalyst and photosensitizer in the polymer were easily recycled for use with the ionic liquid solvent without any loss of catalytic activity. PMID- 25118043 TI - Contrasting diversity of epibiotic bacteria and surrounding bacterioplankton of a common submerged macrophyte, Potamogeton crispus, in freshwater lakes. AB - Epibiotic bacteria on surfaces of submerged macrophytes play important roles in the ecological processes of shallow lakes. However, their community ecology and dynamics are far from understood in comparison with those of bacterioplankton. Here, we conducted a comparative study of the species diversity and composition of epibiotic bacterial and the surrounding bacterioplankton communities of a common submerged macrophyte, Potamogeton crispus, in 12 lakes at a regional scale in China. We found that in different freshwater lakes, epibiotic bacteria possessed higher taxonomic richness than bacterioplankton did. There existed a marked divergence in the community structure between epibiotic bacteria and bacterioplankton. Alphaproteobacteria was the most dominant group for epibiotic bacteria, whereas Actinobacteria dominated bacterioplankton. Although variations in both bacterioplankton and epibiotic bacterial community compositions in different lakes were better explained by environmental than spatial factors, both environment and space had more intensified effects on epibiotic bacteria. This implied more complex and diverse 'microhabitats' for epibiotic bacteria on surfaces of submerged macrophytes, which may lead to higher variations of epibiotic bacteria than bacterioplankton. Our study suggested that epibiotic bacteria exhibited higher diversity and distinct community composition than the surrounding bacterioplankton. More attention should be focused on the productive and diverse microbial habitats on submerged macrophytes. PMID- 25118046 TI - Four pediatric patients with autosomal recessive polycystic kidney disease developed new-onset diabetes after renal transplantation. AB - NODAT is increasingly prevalent. Compared with adult recipients, NODAT is less prevalent in pediatric renal transplant recipients; however, some risk factors for its development in young patients have been defined. We report four pediatric renal transplant recipients with ARPKD who developed NODAT. We review the current pediatric NODAT literature and hypothesize that ARPKD may be an additional risk factor for NODAT. PMID- 25118050 TI - Of early animals, anaerobic mitochondria, and a modern sponge. AB - The origin and early evolution of animals marks an important event in life's history. This event is historically associated with an important variable in Earth history - oxygen. One view has it that an increase in oceanic oxygen levels at the end of the Neoproterozoic Era (roughly 600 million years ago) allowed animals to become large and leave fossils. How important was oxygen for the process of early animal evolution? New data show that some modern sponges can survive for several weeks at low oxygen levels. Many groups of animals have mechanisms to cope with low oxygen or anoxia, and very often, mitochondria - organelles usually associated with oxygen - are involved in anaerobic energy metabolism in animals. It is a good time to refresh our memory about the anaerobic capacities of mitochondria in modern animals and how that might relate to the ecology of early metazoans. PMID- 25118051 TI - Expertise in video game playing is associated with reduced valence-concordant emotional expressivity. AB - In carefully selected groups of video game playing (VGP) experts and nonexperts, we examined valence-concordant emotional expressivity. We measured electromyographic (EMG) activity over the corrugator supercilii muscle while participants viewed pleasant, neutral, and unpleasant pictures. Potential group differences concerning valence-concordant expressivity may arise from differences concerning the participants' emotional reactivity. To control for such differences, we concomitantly measured skin conductance response (SCR) and, in a separate affect misattribution procedure (AMP), valence transfer from the same set of stimuli. Importantly, we found attenuated valence-concordant EMG activity over the corrugator supercilii muscle in VGP experts compared to nonexperts, but no differences were evident concerning SCR or valence transfer in the AMP. The findings suggest that expertise in VGP is particularly associated with reduced valence-concordant emotional expressivity. PMID- 25118052 TI - Increased myo-inositol in parietal white and gray matter as a biomarker of poor prognosis in neuropsychiatric lupus: a case report. AB - Neuropsychiatric manifestations can be a serious complication of systemic lupus erythematosus, affecting nearly 56% of these patients. Frequently, acceptable clinical outcome is observed in neurolupus with immunosuppressive therapy. Different metabolites identified with MR spectroscopy may be associated with modifications in the natural history of this disease, specifically in the central nervous system. We report a case of neurolupus with progressive neurologic impairment despite aggressive immunosuppressive treatment. We describe clinical features, laboratory and MRI results, as well as characteristic findings on MR spectroscopy. Serial MRI identified atrophy of the left temporal lobe. MR spectroscopy showed an increase of myo-inositol/creatine ratio intensity, accompanied by a decrease of N-acetylaspartate/creatine ratio in both parietal white and gray matter. During follow-up, the patient developed progressive cognitive deficiency despite the intensification of therapy. Neurolupus manifestations are common and immunosuppressive treatment often avoids severe complications. Characteristic findings on MR spectroscopy may be useful for clinicians to determine poor prognosis and resistance to therapy. PMID- 25118053 TI - Higher BMI in heart failure patients is associated with longer survival only in the absence of diabetes. AB - AIMS: Obesity and diabetes are associated with an increased cardiovascular risk and mortality. Paradoxically, higher BMI is associated with longer survival in heart failure patients. The association between BMI and risk of death in heart failure patients depends on diabetes history. METHODS: We conducted a retrospective cohort study on 503 ambulatory systolic heart failure patients attending a heart failure clinic, based on abstraction of data from clinical records. Patients were compared according to diabetes history. BMI was analyzed as a continuous variable and dichotomized using 25 kg/m as cut-off. Patients' follow-up was censored at 5 years and all-cause death was the endpoint under study. RESULTS: The median age was 69 years and 68% were men; 184 (36.6%) patients had diabetes upon referral. During follow-up, 95 nondiabetic and 69 diabetic patients died. Higher BMI was associated with longer survival in the whole sample, but this association was only reproduced in the subgroup of patients without diabetes [hazard ratio = 0.93; 95% confidence interval (CI): 0.89-0.98 per kg/m vs. hazard ratio = 0.99; 95% CI: 0.94-1.04 in diabetic patients; P for interaction = 0.009]. BMI below 25 kg/m increased the risk of death by 1.90-fold (95% CI: 1.23-2.94) with a null association in diabetic patients (P for interaction = 0.012). The association between BMI and mortality in nondiabetic heart failure patients was independent of other predictors of prognosis. CONCLUSION: The reported obesity paradox in heart failure can only be observed in nondiabetic patients. PMID- 25118054 TI - A national Programme Budgeting and Marginal Analysis (PBMA) of health improvement spending across Wales: disinvestment and reinvestment across the life course. AB - BACKGROUND: Wales faces serious public health challenges, with relatively low life expectancies and wide inequalities in life expectancy with associated pressures on the National Health Service (NHS) at a time of financial recession. This has led to growing recognition of the need to better understand the range of health improvement and prevention programmes across Welsh Government, NHS, local government and voluntary sector agencies. METHODS: The Minister for Health and Social Care commissioned Public Health Wales, the single national public health organisation, to establish a Health Improvement Advisory Group, to oversee a Programme Budgeting and Marginal Analysis (PBMA) expert panel. The panel drew on evidence from a range of sources to explore potential alternative modes of health improvement initiative delivery across Wales. Electronic voting was used to agree an appropriate time horizon for health improvement programme outcomes, main objective of the health improvement review and criteria for evaluating candidate services for disinvestment and investment. The panel also used electronic voting to state whether they wished to disinvest or invest in a candidate service. RESULTS: The review identified a budget of L15.1 million, spanning 10 Welsh Government priority areas, and 6 life course stages. Due to lack of evidence the panel recommended total disinvestment in 7 out of 25 initiatives releasing L1.5 million of resources, and partial disinvestment in a further 3 interventions releasing L7.3 million of resources. The panel did not recommend increasing investment in any of the 25 initiatives under review. Marginal analyses prioritised child health, mental health and wellbeing and tobacco control as key areas for investment. CONCLUSIONS: Wales is championing a concept of "prudent healthcare". The PBMA exercise undertaken here was a transparent evidence-based tool to reach decisions about potential for disinvestment and reinvestment in health improvement strategies. It also demonstrates the potential wider application at a national level across government public health functions, to ensure resources are most cost-effectively deployed, with due consideration for equity. PMID- 25118055 TI - Fitness for entering a simple exercise program and mortality: a study corollary to the exercise introduction to enhance performance in dialysis (EXCITE) trial. AB - BACKGROUND/AIMS: In this corollary analysis of the EXCITE study, we looked at possible differences in baseline risk factors and mortality between subjects excluded from the trial because non-eligible (n=216) or because eligible but refusing to participate (n=116). METHODS: Baseline characteristics and mortality data were recorded. Survival and independent predictors of mortality were assessed by Kaplan-Meier and Cox regression analyses. RESULTS: The incidence rate of mortality was higher in non-eligible vs. eligible non-randomized patients (21.0 vs. 10.9 deaths/100 persons-year; P<0.001). The crude excess risk of death in non-eligible patients (HR 1.96; 95% CI 1.36 to 2.77; P<0.001) was reduced after adjustment for risk factors which differed in the two cohorts including age, blood pressure, phosphate, CRP, smoking, diabetes, triglycerides, cardiovascular comorbidities and history of neoplasia (HR 1.60; 95% CI 1.10 to 2.35; P=0.017) and almost nullified after including in the same model also information on deambulation impairment (HR 1.16; 95% CI 0.75 to 1.80; P=0.513). CONCLUSIONS: Deambulation ability mostly explains the difference in survival rate in non-eligible and eligible non-randomized patients in the EXCITE trial. Extending data analyses and outcome reporting also to subjects not taking part in a trial may be helpful to assess the representability of the study population. PMID- 25118056 TI - Genomic Resources Notes accepted 1 June 2014 - 31 July 2014. AB - This article documents the public availability of transcriptome sequence data, assembled contigs and annotated contigs and ORFS for five anchialine shrimp species (Crustacea: Atyidae and Alpheidae). PMID- 25118057 TI - Microsurgical clipping for recurrent aneurysms after initial endovascular coil embolization. AB - OBJECTIVE: Surgical treatment for recurrent lesions of embolized aneurysms is difficult and challenging for many neurosurgeons because intra-aneurysmal coil masses are sometimes scarred to the wall of the aneurysm or adherent to adjacent vital structures. To assess the efficacy and safety of surgical treatment without coil removal for recurrent aneurysms after previous coil embolization, we retrospectively studied clinical results, angiographic results, and complications in patients treated with additional microsurgical clipping. METHODS: From April 2003 to April 2013, 7 patients with recurrent previous embolized aneurysms underwent microsurgical treatment. RESULTS: This series included 1 man and 6 women receiving endovascular coiling as the first-line treatment. One patient's aneurysm was unruptured, whereas the other 6 were ruptured. The aneurysm locations were posterior communicating (n = 3), anterior communicating (n = 2), ophthalmic (n = 1), and posterior inferior cerebellar (n = 1). The initial sizes ranged from 3-11.5 mm in diameter (mean, 6.6 mm), and the aspect ratios were 1.2 to 3.4 (mean, 1.9). In these aneurysms, the initial coiling result was complete occlusion in 5 patients, and neck remnants in 2 patients. The mechanism underlying aneurysm recurrence was coil compaction in 3 aneurysms, aneurysm regrowth in 3 aneurysms, and fundal migration in 1 aneurysm. The median recurrence latency was 28.8 months (range, 0.7-115 months). Microsurgical clippings without coil removal were used in 6 patients; a parent artery occlusion under bypass protection was done in 1 case with a posterior inferior cerebellar aneurysm. Fenestrated clips in combination with another type of clip were successfully used for 4 of 6 patients who were treated with direct neck clipping. No postoperative morbidity was observed, and postoperative imaging studies revealed complete occlusion of the aneurysms in all cases. There were no recurrences of aneurysms during the follow-up period (mean, 44.7 months; range, 0.5-118 months). CONCLUSIONS: The microsurgical clipping without coil removal for recurrent lesions of embolized aneurysms is effective and safe when it is technically feasible. The tandem clipping in combination with a fenestrated clip is a crucial method for direct neck clipping without coil removal for previously coiled recurrent aneurysms. For unclippable lesions, a parent artery occlusion under bypass protection should be taken into consideration. PMID- 25118058 TI - Gelfoam scaffold for vein prolapse during brain tumor surgery. AB - When resecting gliomas, extra-axial tumors, or their overlying cortex, cortical veins may become suspended over the resection cavity and ultimately prolapse and kink into the cavity, promoting venous thrombosis. To prevent this, we describe a technique to secure a Gelfoam scaffold beneath the cortical vein at the edge of the resection cavity to prevent kinking and possible thrombosis from taking place after tumor removal. Depending on the diameter of the resection cavity, this can be done at 1 or both edges of the resection cavity to prevent prolapse of the vein into the cavity. In our experience with this technique, during the past 10 years, there have been no cases of venous thrombosis after tumor removal on postoperative imaging or clinical examination. PMID- 25118059 TI - Efficacy and safety of subdural drains after burr-hole evacuation of chronic subdural hematomas: systematic review and meta-analysis of randomized controlled trials. AB - OBJECTIVE: To determine whether the use of a subdural drain after burr-hole evacuation of a chronic subdural hematoma is safe and effective in preventing recurrence and subsequent operations, and as such improving functional outcomes. METHODS: The literature search included the following databases: PubMed, the National Institutes of Health/National Library of Medicine, Clinical Trials Registry, CENTRAL (The Cochrane Library), EMBASE, and LILACS. The search was performed in June 2013, and did not have restrictions or filters with regard to language or year of publication. Methodologic quality was assessed through the Jadad's scale. Primary outcomes were recurrence and reoperation rates. Secondary outcomes were functional outcome, mortality, and postoperative complications. Results were presented as pooled Mantel-Haenszel relative risks (RR), with 95% confidence intervals (95% CI). RESULTS: A total of 7 randomized controlled trials were analyzed. Three studies were classified as high methodologic quality and four as low quality. Pooled RR were symptomatic recurrence (RR 0.51; 95% CI 0.36 0.75), reoperation (RR 0.5; 95% CI 0.34-0.74), poor functional outcome (RR 0.61, 95% CI 0.39-0.98), mortality (RR 0.67, 95% CI 0.37-1.22), and postoperative complications (RR 1.28, 95% CI 0.78-2.11). There was no statistically significant heterogeneity within the outcomes. CONCLUSIONS: The meta-analysis demonstrates that the insertion of a subdural drain was associated with a statistically significant reduction in the risk of symptomatic recurrence and the requirement for further surgical intervention of chronic subdural hematoma after surgical evacuation. Furthermore, it was associated with statistically significant improvements in both short-term and long-term functional outcome. PMID- 25118060 TI - Spinal metastases in breast cancer: single center experience. AB - OBJECTIVE: Metastases to the spine are a common manifestation of breast cancer leading to considerable reduction in the patient's quality of life. Physicians must consider the different treatments available to decrease pain, reduce tumor burden, and ensure spinal stability to prevent neurological compromises. The first objective of this study is to analyze the epidemiology and outcomes of patients with spinal metastases from breast cancer and describe changes over time in these lesions. The second objective is to establish the current treatment of spinal metastases in this type of cancer. METHODS: A total of 140 patients with breast cancer and spinal metastasis involvement were studied retrospectively. Demographic, clinical, and radiologic parameters were assessed, and the effects of systemic and local treatments on spinal metastasis were analyzed. RESULTS: Median patient age at diagnosis of breast cancer was 50 years (19-86 years) and average follow-up was 100 months (4-384 months). Median overall survival after diagnosis of spinal metastasis was 18.6 months. Fractures were present in 24 patients (19.3%) at diagnosis and in up to 60 cases (48.6%) by the end of the study period. CONCLUSIONS: The survival rate was better in patients with spinal metastases who received specific treatment. The evolution from lytic spinal metastasis to mixed and blastic subtypes is observed with adjunctive therapy for spinal metastases (bisphosphonates, radiotherapy). Increased attention must be given for high-grade breast cancer, as spinal metastases declare faster for these stages. This study provides evidence that a multidisciplinary tumor board specifically focusing on bone metastasis is essential to effectively manage patients with breast cancer and spinal metastasis. PMID- 25118061 TI - Endolithic bacterial communities in rock coatings from Karkevagge, Swedish Lapland. AB - Rock coatings in Karkevagge, Swedish Lapland, are widespread and mineralogically diverse. A preliminary study of the rock coatings revealed higher than expected bacterial diversity for an endolithic environment in the arctic. Using 454 Roche pyrosequencing of the 16S rRNA gene, nine rock coating samples from three different coating mineralogies were sequenced. The three coating types include Fe films of goethite and hematite, sulfate crusts of jarosite and gypsum, and aluminum glazes of basaluminite and alunite. Over 20,000 quality sequences were analyzed, and over 2800 operational taxonomic units were identified. Diversity indices and richness estimates confirmed high levels of diversity, particularly in the sulfate crusts with diversity indices at the level of complex soils. Inferred physiology shows the presence of both heterotrophs and autotrophs, with genera of autotrophic Fe and S metabolisms present in at least 2% of the total for each coating type. The most common phyla included Proteobacteria, Acidobacteria, and Actinobacteria - all common soil taxa. Coatings also showed distinct community structure between coating mineralogies. Given the diversity in coating types found in areas receiving the same chemical and environmental inputs, the distinct microbial communities suggest a biological role in coating development. PMID- 25118066 TI - Technological supports to promote choice opportunities by two children with fragile X syndrome and severe to profound developmental disabilities. AB - This study was aimed at assessing whether technological supports (i.e. optic sensors such as photocells) were successful enabling two boys with fragile X syndrome and severe to profound developmental disabilities to perform occupation and choice opportunities. A second goal of the study was to reduce stereotyped behaviours (i.e. hand mouthing and eye poking) exhibited by the participants. Finally, the third purpose of the study was to verify the rehabilitative effects of the intervention program on the indices of happiness of the participants. The study has been conducted according to a non-concurrent multiple baseline design across participants followed by intervention and cross over phases, where the associations between behavioural responses and environmental consequences were systematically inverted. Moreover, a maintenance phase was assessed. The results demonstrated that the technology is useful to facilitate employment and opportunities of choice, showing a growth of the indices of happiness and a decrease of stereotyped behaviours, from both participants involved. Clinical, practical and psychological implications of the findings are discussed. PMID- 25118067 TI - The Effect of Increasing Fruit and Vegetable Consumption on Overall Diet: A Systematic Review and Meta-analysis. AB - Increasing fruit and vegetable (FV) consumption is associated with reduced risk of major diseases. However, it is unclear if health benefits are related to increased micronutrient intake or to improvements in overall diet profile. This review aimed to assess if increasing FV consumption had an impact on diet profile. In the systematic review, 12 studies revealed increases in micronutrient intakes, whilst the meta-analysis confirmed macronutrient findings from the systematic review showing no significant difference between the intervention and control groups in energy (kcals) in seven studies (mean difference = 1 kcals [95% CI = -115, 117]; p = 0.98), significant decreases in total fat (% energy) in five studies (Mean difference = -4% [95% CI = -5, -3]; p = < 0.00001) and significant increases in fiber in six studies (Mean difference = 5.36 g [95% CI = 4, 7]; p = < 0.00001) and total carbohydrate (% energy) in four studies (Mean = 4% [95% CI= 2, 5]; p = < 0.00001). In conclusion, results indicate that increased FV consumption increases micronutrient, carbohydrate and fiber intakes and possibly reduces fat intake, with no overall effect on energy intake. Therefore health benefits may act through an improvement in overall diet profile alongside increased micronutrient intakes. PMID- 25118068 TI - Synchronous tRNA movements during translocation on the ribosome are orchestrated by elongation factor G and GTP hydrolysis. AB - The translocation of tRNAs through the ribosome proceeds through numerous small steps in which tRNAs gradually shift their positions on the small and large ribosomal subunits. The most urgent questions are: (i) whether these intermediates are important; (ii) how the ribosomal translocase, the GTPase elongation factor G (EF-G), promotes directed movement; and (iii) how the energy of GTP hydrolysis is coupled to movement. In the light of recent advances in biophysical and structural studies, we argue that intermediate states of translocation are snapshots of dynamic fluctuations that guide the movement. In contrast to current models of stepwise translocation, kinetic evidence shows that the tRNAs move synchronously on the two ribosomal subunits in a rapid reaction orchestrated by EF-G and GTP hydrolysis. EF-G combines the energy regimes of a GTPase and a motor protein and facilitates tRNA movement by a combination of directed Brownian ratchet and power stroke mechanisms. PMID- 25118070 TI - Challenges for paediatric transplantation in Africa. AB - Transplantation is the accepted mode of treatment for patients with end-stage organ disease affecting the heart, lungs, kidney, pancreas, liver and intestine. Long-term outcomes have significantly improved and the aim of management is no longer only long-term survival, but also focuses on quality of life especially in children. Transplantation in Africa faces a number of challenges including wide socioeconomic disparity, lack of legislation around brain death and organ donation in many countries, shortage of skilled medical personnel and facilities, infectious disease burden and insecure access to and monitoring of immunosuppression. Whilst there is a need for transplantation, the establishment and sustainability of transplant programmes require careful planning with national government and institutional support. Legislation regarding brain death diagnosis and organ retrieval/donation; appropriate training of the transplant team; and transparent and equitable criteria for organ allocation are important to establish before embarking on a transplant programme. Establishing sustainable, self-sufficient transplant programmes in Africa with equal access to all citizens is an important step towards curtailing transplant tourism and organ trafficking and has a further beneficial effect in raising the level of medical and surgical care in these countries. PMID- 25118069 TI - How does conversion of natural tropical rainforest ecosystems affect soil bacterial and fungal communities in the Nile river watershed of Uganda? AB - Uganda's forests are globally important for their conservation values but are under pressure from increasing human population and consumption. In this study, we examine how conversion of natural forest affects soil bacterial and fungal communities. Comparisons in paired natural forest and human-converted sites among four locations indicated that natural forest soils consistently had higher pH, organic carbon, nitrogen, and calcium, although variation among sites was large. Despite these differences, no effect on the diversity of dominant taxa for either bacterial or fungal communities was detected, using polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE). Composition of fungal communities did generally appear different in converted sites, but surprisingly, we did not observe a consistent pattern among sites. The spatial distribution of some taxa and community composition was associated with soil pH, organic carbon, phosphorus and sodium, suggesting that changes in soil communities were nuanced and require more robust metagenomic methods to understand the various components of the community. Given the close geographic proximity of the paired sampling sites, the similarity between natural and converted sites might be due to continued dispersal between treatments. Fungal communities showed greater environmental differentiation than bacterial communities, particularly according to soil pH. We detected biotic homogenization in converted ecosystems and substantial contribution of beta-diversity to total diversity, indicating considerable geographic structure in soil biota in these forest communities. Overall, our results suggest that soil microbial communities are relatively resilient to forest conversion and despite a substantial and consistent change in the soil environment, the effects of conversion differed widely among sites. The substantial difference in soil chemistry, with generally lower nutrient quantity in converted sites, does bring into question, how long this resilience will last. PMID- 25118071 TI - An evaluation of traffic-awareness campaign videos: empathy induction is associated with brain function within superior temporal sulcus. AB - Acting appropriately within social contexts requires an ability to appreciate others' mental and emotional states. Indeed, some campaign programs designed to reduce anti-social behaviour seek to elicit empathy for the victims. The effectiveness of these campaigns can be evaluated according to the degree to which they induce such responses, but by applying neuroscientific techniques this can be done at the behavioural and neurophysiological level. Neuroimaging studies aimed at identifying the neural mechanisms behind such socio-cognitive and emotional processes frequently reveal the role of the superior temporal sulcus (STS). We applied this knowledge to assess the effectiveness of traffic-awareness campaign adverts to induce empathic expression. Functional magnetic resonance imaging (fMRI) data were acquired from 20 healthy male volunteers as they watched these campaign videos consisting of a dramatic sequence of events and catastrophic endings, and control videos without such dramatic endings. Among other structures, a significantly greater neural response was observed within bilateral STS, particularly within the right hemisphere, during the observation of campaign relative to control videos. Furthermore, activation in these brain regions correlated with the subjects' empathic expression. Our results develop our understanding of the role of STS in social cognition. Moreover, our data demonstrate the utility of neuroscientific methods when evaluating the effectiveness of campaign videos in terms of their ability to elicit empathic responses. Our study also demonstrates the utility of these specific stimuli for future neuroscientific research. PMID- 25118073 TI - Forced sex, rape and sexual exploitation: attitudes and experiences of high school students in South Kivu, Democratic Republic of Congo. AB - This paper reports on fieldwork carried out in 2011 with the aim of investigating the attitudes and reported behaviour of Congolese high school students concerning sexual relationships. A total of 56 boys and girls aged 16-20 from two urban and two rural high schools in South Kivu Province took part in focus groups, and 40 of these were subsequently interviewed individually. The majority of boys felt that they were entitled to sex from their girlfriends and that if persuasion was unsuccessful, the use of force was legitimate; this, in their minds, did not constitute rape. Girls, on the other hand, were clear that such forced sex was rape. However it may be understood, rape was perceived as having increased in recent years and was explained by weak legal systems, pornography and provocative dressing by girls. Boys were angry at the competition from older, often married, men who were able to provide monetary and other incentives to the girls. PMID- 25118074 TI - Suicide in Sri Lanka 1975-2012: age, period and cohort analysis of police and hospital data. AB - BACKGROUND: Sri Lanka has experienced major changes in its suicide rates since the 1970s, and in 1995 it had one of the highest rates in the world. Subsequent reductions in Sri Lanka's suicide rates have been attributed to the introduction of restrictions on the availability of highly toxic pesticides. We investigate these changes in suicide rates in relation to age, gender, method specific trends and birth-cohort and period effects, with the aim of informing preventative strategies. METHODS: Secular trends of suicide in relation to age, sex, method, birth-cohort and period effects were investigated graphically using police data (1975-2012). Poisoning case-fatality was investigated using national hospital admission data (2004-2010). RESULTS: There were marked changes to the age-, gender- and method-specific incidence of suicide over the study period. Year on year declines in rates began in 17-25 year olds in the early 1980s. Reduction in older age groups followed and falls in all age groups occurred after all class I (the most toxic) pesticides were banned. Distinct changes in the age/gender pattern of suicide are observed: in the 1980s suicide rates were highest in 21-35 year old men; by the 2000s, this pattern had reversed with a stepwise increase in male rates with increasing age. Throughout the study period female rates were highest in 17-25 year olds. There has been a rise in suicide by hanging, though this rise is relatively small in relation to the marked decline in self-poisoning deaths. The patterns of suicides are more consistent with a period rather than birth-cohort effect. CONCLUSIONS: The epidemiology of suicide in Sri Lanka has changed noticeably in the last 30 years. The introduction of pesticide regulations in Sri Lanka coincides with a reduction in suicide rates, with evidence of limited method substitution. PMID- 25118072 TI - An evolving perspective about the origins of childhood undernutrition and nutritional interventions that includes the gut microbiome. AB - The Sackler Institute for Nutrition Science and the World Health Organization (WHO) have worked together to formulate a research agenda for nutrition science. Undernutrition of children has profound effects on health, development, and achievement of full human capacity. Undernutrition is not simply caused by a lack of food, but results from a complex interplay of intra- and intergenerational factors. Representative preclinical models and comprehensive well-controlled longitudinal clinical studies are needed to further understand the contributions and the interrelationships among these factors and to develop interventions that are effective and durable. This paper summarizes work on mechanisms underlying the varied manifestations of childhood undernutrition and discusses current gaps in knowledge and challenges to our understanding of undernutrition and infection/immunity throughout the human life cycle, focusing on early childhood growth. It proposes a series of basic and clinical studies to address this global health challenge. PMID- 25118075 TI - Viunalikeviruses are environmentally common agents of horizontal gene transfer in pathogens and biocontrol bacteria. AB - Bacteriophages have been used as natural biocontrol and therapeutic agents, but also as biotechnological tools for bacterial engineering. We showed recently that the transducing bacteriophage phiMAM1 is a ViI-like phage and a member of the new genus, 'Viunalikevirus'. Here, we show that four additional ViI-like phages and three new environmentally isolated viunalikeviruses, all infecting plant and human pathogens, are very efficient generalised transducers capable of transducing chromosomal markers at frequencies of up to 10(-4) transductants per plaque-forming unit. We also demonstrate the interstrain transduction of plasmids and chromosomal markers, including genes involved in anabolism, genes for virulence and genes encoding secondary metabolites involved in biocontrol. We propose that all viunalikeviruses are likely to perform efficient horizontal gene transfer. Viunalikeviruses therefore represent useful agents for functional genomics and bacterial engineering, and for chemical and synthetic biology studies, but could be viewed as inappropriate choices for phage therapy. PMID- 25118077 TI - The quantified patient: a patient participatory culture. AB - The Quantified Self Movement, which aims to improve various aspects of life and health through recording and reviewing daily activities and biometrics, is a new and upcoming practice of self monitoring that holds much promise. Now, the most underutilized resource in ambulatory health care, the patient, can participate like never before, and the patient's Quantified Self can be directly monitored and remotely accessed by health care professionals. PMID- 25118076 TI - Physical performance and clinical outcomes in dialysis patients: a secondary analysis of the EXCITE trial. AB - BACKGROUND/AIMS: Scarce physical activity predicts shorter survival in dialysis patients. However, the relationship between physical (motor) fitness and clinical outcomes has never been tested in these patients. METHODS: We tested the predictive power of an established metric of motor fitness, the Six-Minute Walking Test (6MWT), for death, cardiovascular events and hospitalization in 296 dialysis patients who took part in the trial EXCITE (ClinicalTrials.gov Identifier: NCT01255969). RESULTS: During follow up 69 patients died, 90 had fatal and non-fatal cardiovascular events, 159 were hospitalized and 182 patients had the composite outcome. In multivariate Cox models - including the study allocation arm and classical and non-classical risk factors - an increase of 20 walked metres during the 6MWT was associated to a 6% reduction of the risk for the composite end-point (P=0.001) and a similar relationship existed between the 6MWT, mortality (P<0.001) and hospitalizations (P=0.03). A similar trend was observed for cardiovascular events but this relationship did not reach statistical significance (P=0.09). CONCLUSIONS: Poor physical performance predicts a high risk of mortality, cardiovascular events and hospitalizations in dialysis patients. Future studies, including phase-2 EXCITE, will assess whether improving motor fitness may translate into better clinical outcomes in this high risk population. PMID- 25118078 TI - Re: Self TH, Patterson SJ, Headley AS, et al. Action plans to reduce hospitalizations for chronic obstructive pulmonary disease exacerbations: focus on oral corticosteroids. Curr Med Res Opin 2014;30(12):2607-15. PMID- 25118079 TI - Mirtazapine associated with drug-related thrombocytopenia: a case report. PMID- 25118080 TI - Revisiting the "cheese reaction": more than just a hypertensive crisis? PMID- 25118081 TI - Serpentine tongue syndrome associated with risperidone long-acting injection treatment. PMID- 25118082 TI - Risperidone-associated urinary incontinence in patients with autistic disorder with mental retardation. AB - We report several cases in which patients with autistic disorder with mental retardation who received risperidone experienced urinary incontinence. We retrospectively investigated the medical records of patients housed in facilities for patients with autistic disorder with mental retardation. Those who had undergone a medical examination at a hospital in Tokyo from April 1999 to March 2009 were included in the study.Retrospective data were gathered including age, sex, IQ, birth weight, dosage of risperidone, urinary density, as well as existence of urinary and fecal incontinence. We divided the participants into those who did and did not experience urinary incontinence after taking risperidone and compared the 2 groups. Risperidone had been prescribed to 35 patients. In spite of the fact that no patient had a history of urinary incontinence, 14 patients experienced urinary incontinence after receiving risperidone. Moreover, 4 of these 14 patients also had fecal incontinence. Among the variables we examined, the only significant difference between groups was in sex, with significantly more women experiencing incontinence compared with men. When the dose of risperidone was reduced or the patients switched to other drugs, urinary incontinence of the patients improved.Hence, risperidone may have a casual relationship with urinary incontinence. Further research is needed to understand the pathophysiology of possible effect. PMID- 25118083 TI - Reboxetine adjuvant therapy in patients with schizophrenia showing a suboptimal response to clozapine: a 12-week, open-label, pilot study. AB - The present 12-week open-label uncontrolled trial was aimed to explore the efficacy of reboxetine add-on pharmacotherapy on clinical symptoms and cognitive functioning in 15 patients with schizophrenia with suboptimal response (mean [SD] Brief Psychiatric Rating Scale baseline total score, 32.2 [5.4]) despite receiving clozapine monotherapy at the highest tolerated dosage. The results obtained evidenced that reboxetine at a dosage of 4 mg/d mildly reduced only depressive symptoms (Calgary Depression Scale for Schizophrenia: P = 0.035, Cohen d = 0.7), whereas worsening of performances on phonemic fluency (P = 0.012, Cohen d = 0.5) was observed. After Bonferroni correction, changes at the Calgary Depression Scale for Schizophrenia and at the Verbal Fluency Task were not further confirmed.The results obtained indicate that reboxetine seemed to be scarcely effective for reducing clinical symptoms in patients with schizophrenia who have had an incomplete clinical response to clozapine. Regarding cognitive functioning, in our sample, a trend to experience cognitive impairment in the examined domains was observed, as confirmed by a mild worsening of performances on cognitive tasks.Schizophrenia is a heterogeneous disorder with regard to pathophysiology; therefore, data reflecting the mean response of a sample of patients may fail to reveal therapeutic effects. More research is needed to better identify subgroups of patients with peculiar features, which may account for responsivity to experimental medications and augmentation strategies. PMID- 25118084 TI - STAR--people-powered prioritization: a 21st-century solution to allocation headaches. AB - The aim of cost effectiveness analysis (CEA) is to inform the allocation of scarce resources. CEA is routinely used in assessing the cost-effectiveness of specific health technologies by agencies such as the National Institute for Health and Clinical Excellence (NICE) in England and Wales. But there is extensive evidence that because of barriers of accessibility and acceptability, CEA has not been used by local health planners in their annual task of allocating fixed budgets to a wide range of types of health care. This paper argues that these planners can use Socio Technical Allocation of Resources (STAR) for that task. STAR builds on the principles of CEA and the practice of program budgeting and marginal analysis. STAR uses requisite models to assess the cost effectiveness of all interventions considered for resource reallocation by explicitly applying the theory of health economics to evidence of scale, costs, and benefits, with deliberation facilitated through an interactive social process of engaging key stakeholders. In that social process, the stakeholders generate missing estimates of scale, costs, and benefits of the interventions; develop visual models of their relative cost-effectiveness; and interpret the results. We demonstrate the feasibility of STAR by showing how it was used by a local health planning agency of the English National Health Service, the Isle of Wight Primary Care Trust, to allocate a fixed budget in 2008 and 2009. PMID- 25118085 TI - Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial. AB - Calcium and vitamin D are essential nutrients for bone health. Periods of activity with repetitive mechanical loading, such as military training, may result in increases in parathyroid hormone (PTH), a key regulator of Ca metabolism, and may be linked to the development of stress fractures. Previous studies indicate that consumption of a Ca and vitamin D supplement may reduce stress fracture risk in female military personnel during initial military training, but circulating markers of Ca and bone metabolism and measures of bone density and strength have not been determined. This randomized, double-blind, placebo-controlled trial sought to determine the effects of providing supplemental Ca and vitamin D (Ca+Vit D, 2000mg and 1000IU/d, respectively), delivered as 2 snack bars per day throughout 9weeks of Army initial military training (or basic combat training, BCT) on PTH, vitamin D status, and measures of bone density and strength in personnel undergoing BCT, as well as independent effects of BCT on bone parameters. A total of 156 men and 87 women enrolled in Army BCT (Fort Sill, OK; 34.7 degrees N latitude) volunteered for this study. Anthropometric, biochemical, and dietary intake data were collected pre- and post BCT. In addition, peripheral quantitative computed tomography was utilized to assess tibia bone density and strength in a subset of volunteers (n=46). Consumption of supplemental Ca+Vit D increased circulating ionized Ca (group-by time, P=0.022), maintained PTH (group-by-time, P=0.032), and increased the osteoprotegerin:RANKL ratio (group-by-time, P=0.006). Consistent with the biochemical markers, Ca+Vit D improved vBMD (group-by-time, P=0.024) at the 4% site and cortical BMC (group-by-time, P=0.028) and thickness (group-by-time, P=0.013) at the 14% site compared to placebo. These data demonstrate the benefit of supplemental Ca and vitamin D for maintaining bone health during periods of elevated bone turnover, such as initial military training. This trial was registered with ClincialTrials.gov, NCT01617109. PMID- 25118087 TI - Fine particulate matter and risk of preterm birth and pre-labor rupture of membranes in Perth, Western Australia 1997-2007: a longitudinal study. AB - OBJECTIVE: A recent longitudinal study reported an association between fine particulate (PM2.5) exposure and preterm birth (PTB) in a US cohort. We applied the same design to an Australian cohort to investigate associations with PTB and pre-labor rupture of membranes (PROM). METHODS: From 287,680 births, we selected 39,189 women who had singleton births at least twice in Western Australia in 1997 2007 (n=86,844 births). Analyses matched pregnancies to the same women with conditional logistic regression. RESULTS: For PROM adjusted odds ratios (ORs) for a 1 MUg/m(3) increase in PM2.5 in the first trimester, second trimester, third trimester, and whole pregnancy were 1.00 (95% confidence interval (CI): 0.97, 1.03), 1.03 (95% CI: 1.00, 1.06), 1.02 (95% CI: 1.00, 1.05), and 1.02 (95% CI: 0.99, 1.05) respectively. For PTB, corresponding ORs were 1.00 (95% CI: 0.96, 1.04), 1.00 (95% CI: 0.96, 1.04), 0.98 (95% CI: 0.94, 1.02), and 0.99 (95% CI: 0.95, 1.04) respectively. CONCLUSION: Risk of PROM was greater for pregnancies with elevated PM2.5 exposure in the second trimester than were other pregnancies to the same Australian women at lower exposure. There was insufficient evidence for an association with PTB, indicating that a longer time period might be needed to observe an association if a causal effect exists. PMID- 25118089 TI - Physical activity and renal transplantation. AB - Renal transplantation is burdened by high cardiovascular risk because of increased prevalence of traditional and disease-specific cardiovascular risk factors and, consequently, patients are affected by greater morbidity and mortality. In renal transplanted patients, healthy lifestyle and physical activity are recommended to improve overall morbidity and cardiovascular outcomes. According to METs (Metabolic Equivalent Task; i.e. the amount of energy consumed while sitting at rest), physical activities are classified as sedentary (<3.0 METs), of moderate-(3.0 to 5.9 METs) or vigorous-intensity (>= 6.0 METs). Guidelines suggest for patients with chronic kidney disease an amount of physical activity of at least 30 minutes of moderate-intensity activity five times per week (min 450 MET-minutes/week). Data on physical activity in renal transplanted patients, however, are limited and have been mainly obtained by mean of non objective methods. Available data suggest that physical activity is low either at the start or during renal transplantation and this may be associated with poor patient and graft outcomes. Therefore, in renal transplanted patients more data on physical activity obtained with objective, accelerometer-based methods are needed. In the meanwhile, physical activity have to be considered as an essential part of the medical care for renal transplanted recipients. PMID- 25118090 TI - Low-alcohol Beers: Flavor Compounds, Defects, and Improvement Strategies. AB - Beer consumers are accustomed to a product that offers a pleasant and well defined taste. However, in alcohol-free and alcohol-reduced beers these characteristics are totally different from those in regular beer. Therefore, it is important to evaluate and determine the different flavor compounds that affect organoleptic characteristics to obtain a product that does not contain off flavors, or taste of grass or wort. The taste defects in alcohol-free beer are mainly attributed to loss of aromatic esters, insufficient aldehydes, reduction or loss of different alcohols, and an indeterminate change in any of its compounds during the dealcoholization process. The dealcoholization processes that are commonly used to reduce the alcohol content in beer are shown, as well as the negative consequences of these processes to beer flavor. Possible strategies to circumvent such negative consequences are suggested. PMID- 25118088 TI - A PBPK model to estimate PCDD/F levels in adipose tissue: comparison with experimental values of residents near a hazardous waste incinerator. AB - This study was aimed at determining the concentrations of polychlorinated dibenzo p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in 15 samples of adipose tissue from subjects who had been living in the vicinity of a hazardous waste incinerator (HWI). The results were compared with levels obtained in previous surveys carried out in 1998 (baseline study), 2002 and 2007. The current (2013) concentrations of PCDD/Fs in adipose tissue ranged from 2.8 to 46.3 pg WHO-TEQ/g fat (mean and median concentrations: 11.5 and 7.4 pg WHO-TEQ/g fat, respectively), being significantly lower (64%) than those observed in 1998. In contrast, no significant differences in the mean PCDD/F concentrations were noted in the period 2002-2013. The significant decrease of the PCDD/F content in fat, also noted in other biological monitors such as plasma and breast milk, is in agreement with the reduction in the dietary intake of PCDD/Fs found in the same area of study. Similarly to other investigations across Europe, an increase of PCDD/F levels in adipose tissue in relation to age was observed, while no significant differences were noted according to gender. A multicompartmental physiologically-based pharmacokinetic (PBPK) model was also applied to estimate the levels of PCDD/Fs in adipose tissue. When comparing the modeled and experimental concentrations of PCDD/Fs in that tissue, very similar values were obtained for the four surveys, which indicates this can be a reliable tool to predict the internal dose of PCDD/Fs. PMID- 25118086 TI - Prepubertal organochlorine pesticide concentrations and age of pubertal onset among Russian boys. AB - BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p' dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV)>3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with physician-assessed pubertal onset. RESULTS: In adjusted models, boys with higher HCB concentrations had later mean ages of TV>3 mL and P2+ (but not G2+). Mean age at attaining TV>3 mL was delayed 3.6 (95% CI: -2.6, 9.7), 7.9 (95% CI: 1.7, 14.0), and 4.7 months (95% CI: -1.4, 10.9) for HCB Q2, Q3, and Q4, respectively, compared to Q1 (trend p: 0.06). Boys with higher HCB concentrations reached P2+ 0.1 months earlier (95% CI: -5.8, 5.6) for Q2, 4.7 months later (95% CI: -1.0, 10.3) for Q3 and 4.6 months later (95% CI: -1.1, 10.3) for Q4 compared to Q1 (trend p: 0.04). There were no associations of serum beta-HCH and p,p'-DDE concentrations with age of pubertal onset. CONCLUSION: Higher prepubertal serum HCB concentrations were associated with later age of gonadarche and pubarche. PMID- 25118098 TI - Being both and acting 'man': exploring patterns of masculinisation among young same-sex-attracted men in Thailand. AB - Twenty-five same-sex-attracted rural young Thai men were interviewed three times to investigate how their sexual subjectivity changed over an 18-month period after they completed high school and moved into a new life-phase. Many young men grew up with strong gender-based understandings of homosexuality, in which a masculine (top) partner is seen as complementing a feminine (bottom) partner. The discursive division between the masculine and feminine domains became increasingly blurred in the actual practice of dating, forcing the young men to develop new understandings of homosexuality and same-sex relations. The shift from a rural to urban environment, the use of the Internet and the experience of falling in love played important roles in this experimentation with new, increasingly masculine presentations of the self, also influenced by a modern urban masculine aesthetic. The paper concludes that the encounter between 'traditional' gender-based homosexuality and new ideas, in which masculine object choice is important in defining sexual identity leads to a variety of fluid ideas and expressions. This process created confusion among some, and opportunities for exploration of new ways of defining sexual subjectivities among others. PMID- 25118091 TI - Effect evaluation of two types of dementia-specific case conferences in German nursing homes (FallDem) using a stepped-wedge design: study protocol for a randomized controlled trial. AB - BACKGROUND: Case conferences for people with dementia and challenging behaviors (e.g., apathy) are recommended as useful tools that enable staff in nursing homes to understand the behavior of people with this type of disease. Understanding peoples' behaviors is the basis for the initiation of targeted interventions to improve the quality of care for people with dementia. Furthermore, case conferences demonstrate positive effects on burnout, dementia-specific burden, and vocational action competence of the staff. The two likely approaches for conducting case conferences include the following: A) using a structured assessment instrument, which guides the staff in understanding the residents' behaviors and B) using a narrative approach in which the staff must identify the reasons for the residents' behaviors in an unstructured manner. Case conferences are a complex intervention, and evaluating their multiple effects is challenging. The aim of this study protocol was to describe a likely solution for evaluating this type of complex intervention using a special cluster randomized trial. METHODS: In this stepped-wedged cluster randomized trial, the two interventions will be sequentially implemented every three months in a group of 12 nursing homes (clusters) with a minimum of 360 residents over 19 months (7 months of intervention for each cluster and follow-up). The primary outcome is the reduction of challenging behavior (measured with the neuropsychiatric inventory nursing home version [NPI-NH]). Secondary outcomes are residents' quality of life, prescription of psychotropic medications, staff burnout, dementia-related stress, and vocational action competence. The effectiveness of the study will be accompanied by a process evaluation. The primary data will be analyzed using a Bayesian mixed effect model; the secondary data will be analyzed using descriptive statistics and mixed effects models. DISCUSSION: The implementation and effect measurement of complex interventions such as case conferences within a cluster randomized trial are challenging (e.g., complex and intensive training, delayed treatment effect). In this study protocol, the methodological advantages and disadvantages of using the stepped wedge design to answer the research questions are discussed. TRIAL REGISTRATION: http://www.controlled trials.com/ISRCTN20203855; registered 10 July 2013. PMID- 25118092 TI - Myocyte growth, repair, and oxidative stress following pediatric heart transplantation. AB - Cardiac remodeling is associated with plasma biomarkers of fibrinogenesis, inflammation, and oxidative stress, and upregulation of mitogenic, pro-fibrotic, and apoptotic signaling pathways. Our primary objective was to evaluate biomarker and subcellular myocardial changes in pediatric heart transplant recipients. Fifty-two-week prospective, randomized (tacrolimus, Tac, vs. cyclosporine, CsA), open-label, parallel group study. Serial myocardial biopsies were probed for mitogenic and pro-inflammatory proteins. Plasma biomarkers of oxidative stress (F2alpha isoprostanes, nitrotyrosine), and inflammation and oxidation (hsCRP and cystatin-C) were measured. Nine of 11 randomized patients completed the study (four Tac, five CsA). Mean levels of F2alpha isoprostanes, hsCRP, and cystatin-C were maximal at Week 2. Peak activation of all MAP kinases in myocardial tissue was maximal at Week 10; no association was seen with rejection. Cardiac Bax/Bcl-2 levels (index of apoptosis) correlated negatively with F2alpha isoprostanes at Week 2 (r = -0.88) and with hsCRP at Week 52 (r = -0.67). At Week 52, hsCRP levels correlated positively with molecular indices of cardiac cell growth. We found evidence of systemic and myocardial oxidative damage and inflammation early posttransplant, which may be related to the remodeling process. Further study is needed to better understand the cardiac and systemic repair processes following pediatric heart transplantation. PMID- 25118100 TI - Molecular phylogeny of Asian Meconopsis based on nuclear ribosomal and chloroplast DNA sequence data. AB - The taxonomy and phylogeny of Asian Meconopsis (Himalayan blue poppy) remain largely unresolved. We used the internal transcribed spacer (ITS) region of nuclear ribosomal DNA (nrDNA) and the chloroplast DNA (cpDNA) trnL-F region for phylogenetic reconstruction of Meconopsis and its close relatives Papaver, Roemeria, and Stylomecon. We identified five main clades, which were well supported in the gene trees reconstructed with the nrDNA ITS and cpDNA trnL-F sequences. We found that 41 species of Asian Meconopsis did not constitute a monophyletic clade, but formed two solid clades (I and V) separated in the phylogenetic tree by three clades (II, III and IV) of Papaver and its allies. Clade V includes only four Asian Meconopsis species, with the remaining 90 percent of Asian species included in clade I. In this core Asian Meconopsis clade, five subclades (Ia-Ie) were recognized in the nrDNA ITS tree. Three species (Meconopsis discigera, M. pinnatifolia, and M. torquata) of subgenus Discogyne were imbedded in subclade Ia, indicating that the present definition of subgenera in Meconopsis should be rejected. These subclades are inconsistent with any series or sections of the present classifications, suggesting that classifications of the genus should be completely revised. Finally, proposals for further revision of the genus Meconopsis were put forward based on molecular, morphological, and biogeographical evidences. PMID- 25118099 TI - The rise of mortality from mental and neurological diseases in Europe, 1979-2009: observational study. AB - BACKGROUND: We studied recent trends in mortality from seven mental and neurological conditions and their determinants in 41 European countries. METHODS: Age-standardized mortality rates were analysed using standard methods of descriptive epidemiology, and were related to cultural, economic and health care indicators using regression analysis. RESULTS: Rising mortality from mental and neurological conditions is seen in most European countries, and is mainly due to rising mortality from dementias. Mortality from psychoactive substance use and Parkinson's disease has also risen in several countries. Mortality from dementias has risen particularly strongly in Finland, Iceland, Malta, Netherlands, Spain, Sweden and the United Kingdom, and is positively associated with self-expression values, average income, health care expenditure and life expectancy, but only the first has an independent effect. CONCLUSIONS: Although trends in mortality from dementias have probably been affected by changes in cause-of-death classification, the high level of mortality from these conditions in a number of vanguard countries suggests that it is now among the most frequent causes of death in high-income countries. Recognition of dementias as a cause of death, and/or refraining from life-saving treatment for patients with dementia, appear to be strongly dependent on cultural values. PMID- 25118102 TI - Growing the seeds sown by Piero Sensi. AB - Piero Sensi is probably known primarily for his role in the discovery of rifamycin and for developing it to be a drug of fundamental importance in the treatment of tuberculosis. He has also contributed to promote screening programs of microbial products and research approaches for antibacterial agents that have been further developed up to the present day. This paper reports a sequence of discovery approaches, failures and successes that spans for about 50 years and is still in progress. PMID- 25118101 TI - Follicle stimulating hormone receptor in mesenchymal stem cells integrates effects of glycoprotein reproductive hormones. AB - Previously we reported that follicle stimulating hormone (FSH) affects bone degradation in human cells and in follicle stimulating hormone receptor (FSH-R) null mice. Here we describe a FSH-R knockout bone-formation phenotype. We used mesenchymal stem cells (MSCs), osteoblast precursors that express FSH-R, to determine whether FSH regulates bone formation. FSH stimulates MSC cell adhesion 1-3 h and proliferation at 24 h after addition. On the basis of phylogenetic and clinical precedents, we also examined effects of pregnant levels of human chorionic gonadotropin (hCG) on MSCs. We found effects similar to those of FSH, and RNAi knockdown of FSH-R abrogated both FSH and hCG effects on MSCs. In contrast to effects on MSCs, neither FSH nor hCG had significant effects on osteoblast maturation. Also in MSCs, short-term treatment by FSH and hCG altered signaling pathways for proliferation, including Erk1/2 phosphorylation. Our results show augmentation of MSC proliferation by either FSH at menopausal levels or hCG at normal pregnant levels. We conclude that FSH-R participates in regulation of MSC precursor pools in response to either FSH or hCG, integrating the effects of these two glycoprotein hormones. PMID- 25118103 TI - Resistance to rifampicin: a review. AB - Resistance to rifampicin (RIF) is a broad subject covering not just the mechanism of clinical resistance, nearly always due to a genetic change in the beta subunit of bacterial RNA polymerase (RNAP), but also how studies of resistant polymerases have helped us understand the structure of the enzyme, the intricacies of the transcription process and its role in complex physiological pathways. This review can only scratch the surface of these phenomena. The identification, in strains of Escherichia coli, of the positions within beta of the mutations determining resistance is discussed in some detail, as are mutations in organisms that are therapeutic targets of RIF, in particular Mycobacterium tuberculosis. Interestingly, changes in the same three codons of the consensus sequence occur repeatedly in unrelated RIF-resistant (RIF(r)) clinical isolates of several different bacterial species, and a single mutation predominates in mycobacteria. The utilization of our knowledge of these mutations to develop rapid screening tests for detecting resistance is briefly discussed. Cross-resistance among rifamycins has been a topic of controversy; current thinking is that there is no difference in the susceptibility of RNAP mutants to RIF, rifapentine and rifabutin. Also summarized are intrinsic RIF resistance and other resistance mechanisms. PMID- 25118105 TI - Glycopeptide antibiotics: back to the future. AB - Glycopeptide antibiotics have been a key weapon in the fight against bacterial infections for over half a century, with the progenitors, vancomycin (1) and teicoplanin (2), still used extensively. The increased occurrence of resistance and the effectiveness of these 'last resort' treatments for Gram-positive infections has led to the discovery and clinical development of second generation, semisynthetic lipoglycopeptide derivatives such as telavancin (3), dalbavancin (4) and oritavancin (5), which all possess broader spectra of activity and improved pharmacokinetic properties. Two of these new antibiotics, telavancin (3) and dalbavancin (4), were approved in the past 5 years and the third, oritavancin (5), is awaiting regulatory approval. In this review, the discovery, development and associated resistance of vancomycin (1) and teicoplanin (2), and semi-synthetic glycopeptides, telavancin (3), dalbavancin (4) and oritavancin (5), are detailed. The clinical implications of glycopeptide resistance, especially vancomycin (1), as well as the future prospects for current glycopeptide drugs and the development of new glycopeptides are discussed. PMID- 25118104 TI - Sesquiterpenoids and xanthones derivatives produced by sponge-derived fungus Stachybotry sp. HH1 ZSDS1F1-2. AB - A new (2) and four known (1, 8-10) sesquiterpenoids, two new (3 and 4) and eight known (5-7, 11-15) xanthone derivatives were isolated from the cultures of sponge derived fungus Stachybotry sp. HH1 ZDDS1F1-2. The structure of the compounds 1-15 was determined mainly by analysis of the one-dimensional and two-dimensional NMR spectroscopic data and by analogy with the data of those reported. Compound 1 was confirmed by X-ray crystallography. All the compounds were tested for their cytotoxic, antiinflammatory and antiviral (EV71) effects. Compounds 5, 7 and 11 showed significant cytotoxicity against selected human tumor cell lines. Compounds 3, 4 and 11 also displayed significant inhibitory activity against cycloooxygenase (COX-2). Compounds 4, 5 and 11 showed activities against intestinal virus EV71. PMID- 25118106 TI - New bicyclic hemiacetals from the edible mushroom Ramaria madagascariensis. PMID- 25118108 TI - Spontaneous and induced mutations to rifampicin, streptomycin and spectinomycin resistances in actinomycetes: mutagenic mechanisms and applications for strain improvement. AB - Chemical mutagenesis continues to be an important foundational methodology for the generation of highly productive actinomycete strains for the commercial production of antibiotics and other secondary metabolites. In the past, the determination of frequencies of chemically induced resistance to rifampicin (RifR), spectinomycin (SpcR) and streptomycin (StrR) have served as surrogate markers to monitor the efficiencies and robustness of mutagenic protocols. Recent studies indicate that high level RifR, SpcR and StrR phenotypes map to specific regions of the rpoB, rpsE and rpsL genes, respectively, in actinomycetes. Moreover, mutagenesis to RifR can occur spontaneously at many different sites in rpoB, and all six types of base-pair substitutions, as well as in-frame deletions and insertions, have been observed. The RifR/rpoB system provides a robust method to rank mutagenic protocols, to evaluate mutagen specificity and to study spontaneous mutagenesis mechanisms involved in the maintenance of high G+C content in Streptomyces species and other actinomycetes. PMID- 25118107 TI - Allantopyrone A, an alpha-pyrone metabolite from an endophytic fungus, inhibits the tumor necrosis factor alpha-induced nuclear factor kappaB signaling pathway. AB - Tumor necrosis factor alpha (TNF-alpha) induces the activation of transcription factor nuclear factor kappaB (NF-kappaB), which upregulates a variety of genes, including the gene encoding intercellular adhesion molecule-1 (ICAM-1). Allantopyrone A, a recently identified alpha-pyrone metabolite from an endophytic fungus, was found to inhibit the TNF-alpha-induced expression of ICAM-1 in human lung carcinoma A549 cells. Allantopyrone A also inhibited the TNF-alpha-induced luciferase expression of an NF-kappaB-responsive reporter. In the NF-kappaB signaling pathway, allantopyrone A inhibited the nuclear translocation of NF kappaB subunits as well as the phosphorylation and subsequent degradation of the inhibitor of NF-kappaB (IkappaB) alpha proteins. By contrast, allantopyrone A did not directly affect the catalytic activity of active IkappaB kinase beta. These findings indicate that allantopyrone A inhibits the NF-kappaB signaling pathway at a step upstream of IkappaBalpha phosphorylation. PMID- 25118109 TI - Characterization of swine leukocyte antigen alleles and haplotypes on a novel miniature pig line, Microminipig. AB - Microminipigs are extremely small-sized, novel miniature pigs that were recently developed for medical research. The inbred Microminipigs with defined swine leukocyte antigen (SLA) haplotypes are expected to be useful for allo- and xenotransplantation studies and also for association analyses between SLA haplotypes and immunological traits. To establish SLA-defined Microminipig lines, we characterized the polymorphic SLA alleles for three class I (SLA-1, SLA-2 and SLA-3) and two class II (SLA-DRB1 and SLA-DQB1) genes of 14 parental Microminipigs using a high-resolution nucleotide sequence-based typing method. Eleven class I and II haplotypes, including three recombinant haplotypes, were found in the offspring of the parental Microminipigs. Two class I and class II haplotypes, Hp-31.0 (SLA-1*1502-SLA-3*070102-SLA-2*1601) and Hp-0.37 (SLA DRB1*0701-SLA-DQB1*0502), are novel and have not so far been reported in other pig breeds. Crossover regions were defined by the analysis of 22 microsatellite markers within the SLA class III region of three recombinant haplotypes. The SLA allele and haplotype information of Microminipigs in this study will be useful to establish SLA homozygous lines including three recombinants for transplantation and immunological studies. PMID- 25118110 TI - Development of bead-based suspension array technology for the diagnosis of thalassemia. PMID- 25118111 TI - A TdT-mediated cascade signal amplification strategy based on dendritic DNA matrix for label-free multifunctional electrochemical biosensing. AB - We describe a novel label-free amplified multifunctional strategy of dendritic electrochemical DNA sensor based on terminal deoxynucleotidyl transferase (TdT). We have found that the sequence composition of TdT-yielded DNA is largely dependent on the constitution of substrate deoxynucleotides (dNTPs) pool. After rational design of dNTPs pool and controllable TdT polymerization, dendritic protocol has been developed involving two-type amplification strategies; one is the formation of "trunk" and "branch" of the dendritic electrochemical sensor by TdT amplification; the other is the introduction of nucleic acid functionalized Au nanoparticles (DNA-AuNPs) for multiple branching. The results indicate that the G-rich ssDNA, which is synthesized under the condition of 40% deoxyadenosine triphosphate (dATP) and 60% deoxyguanosine triphosphate (dGTP), can be induced to form a long signal strand to G-quadruples (G4) in the presence of Pb(2+). The electrochemical sensing platform is employed for sequence-specific DNA detection and the detection limit is as low as 1 fM. Our multifunctional strategy is further extended to Pb(2+) detection and thrombin aptasensor. This proposed sensor displays excellent sensitivity and selectivity, and is applied for detection in complicated samples successfully. PMID- 25118112 TI - Physical activity in solid organ transplant recipients: preliminary results of the Italian project. AB - BACKGROUND/AIMS: The role of physical activity in transplanted patients is often underestimated. We discuss the Italian National Transplant Centre experience, which started in 2008 studying transplanted patients involved in sports activities. The study was then developed through a model of cooperation between surgeons, sports physicians and exercise specialists. METHODS: A multicentre study was realized in 120 transplanted patients of which 60 treated with supervised physical activity (three sessions/week of aerobic and strengthening exercises) and 60 controls. We present the results of the first 26 patients (16 males, 10 females; 47.8 +/- 10.0 years; 21 kidney, 5 liver transplanted; time from transplant 2.3 +/- 1.4 years) who completed 12 months of supervised physical activity. RESULTS: Data showed an increase of peak aerobic power (t=4.535; P<0.01) and maximum workload (t=4.665; P<0.01) in the incremental cycling test. Maximum strength of knee extensors (t=2.933; P<0.05) and elbow flexors (t=2.450; P<0.05), and the power of lower limb (t=2.303; P<0.05) significantly increases. Health Related Quality of Life showed a significant improvement. Serum creatinine (1.4 +/- 0.5 vs 1.3 +/- 0.4 mg/dL) and proteinuria (0.10 +/- 0.14 vs 0.08 +/- 0.08 gr/dL) were stable. CONCLUSION: These preliminary results confirm the positive effects of supervised physical exercise. It can be considered as an input to promote other detailed exercise protocols. PMID- 25118113 TI - Application of Glass Transition in Food Processing. AB - The phenomenon of glass transition has been employed to food products to study their stability. It can be applied as an integrated approach along with water activity and physical and chemical changes in food in processing and storage to determine the food stability. Also associated with the changes during agglomeration crystallization, caking, sticking, collapse, oxidation reactions, nonenzymatic browning, and microbial stability of food system. Various techniques such as Differential Scanning Calorimetry, Nuclear Magnetic Resonance, etc. have been developed to determine the glass transition temperature (Tg) of food system. Also, various theories have been applied to explain the concept of Tg and its relation to changes in food system. This review summarizes the understanding of concept of glass transition, its measurement, and application in food technology. PMID- 25118115 TI - Relationship between serum leptin and chronic obstructive pulmonary disease in US adults: results from the third National Health and Nutrition Examination Survey. AB - BACKGROUND: Recent studies suggest an important role for leptin in respiratory immune responses and pathogenesis of inflammatory respiratory diseases. There has been an interest to explore whether leptin plays any role in the pathogenesis of chronic obstructive pulmonary disease (COPD). OBJECTIVE: We conducted a population-based study to evaluate the relationship between serum leptin and COPD in the third US National Health and Nutrition Examination Survey participants. PARTICIPANTS AND DESIGN: Our study group was constituted by 6415 adults who had fasting serum leptin and underwent spirometry measurement. MAIN OUTCOME MEASURES: Serum leptin levels were compared (1) between subjects with normal lung function and those with COPD and (2) among COPD subjects with different severities. RESULTS: Among male participants, 2257 were controls, and 680 had COPD. Compared with controls, COPD subjects were older (62 vs 43 years) and had higher prevalence of smokers (78% vs 58%), lower body mass index (BMI) (26.3 vs 26.9), and higher serum leptin levels (6.6 vs 5.9). For female participants, 2918 were controls, and 560 had COPD. Those with COPD were older (60 vs 43 years) and had lower BMI (26.9 vs 27.7). No differences in serum leptin levels were observed. The independent predictors of COPD in both sexes were age, BMI, and smoking, but not serum leptin. There were no differences in serum leptin among COPD subjects with different severities. CONCLUSIONS: We did not find any significant difference in the levels of serum leptin in subjects with COPD. Our data provide indirect evidence against a major role for serum leptin in the pathogenesis of COPD in humans. PMID- 25118114 TI - Cell-type-specific aptamer and aptamer-small interfering RNA conjugates for targeted human immunodeficiency virus type 1 therapy. AB - Human immunodeficiency virus (HIV) is a virus that causes acquired immunodeficiency syndrome, a chronic and incurable disease of the human immune system. As the standard of care for the patients with HIV-1, current highly active antiretroviral treatment has been therapeutically effective in most patients; however, it is not curative, and highly active antiretroviral treatment is intolerable because of severe adverse effects. Therefore, nucleic acid-based therapeutics, such as antisense oligonucleotide, ribozyme, messenger RNA, RNA interference (RNAi)-based therapeutics, aptamer, and so on, have been actively developed as alternative or adjuvant agents for those chemical antiviral drugs to surmount those drawbacks. The combinatorial use of various antiviral nucleic acids could be more efficacious in blocking viral replication and preventing the emergence of resistant variants. In this regard, RNAi can function as a gene specific therapeutic option for controlling HIV-1 replication. Another type of therapeutic nucleic acid--aptamers--shows promise as a new and potent class of anti-HIV agent and can additionally function as a cell-type-specific delivery vehicle for targeted RNAi. The combined use of small interfering RNA (siRNAs) and aptamers could effectively block viral replication and prevent the emergence of resistant variants. The present review offers a brief overview of the use of cell type-specific aptamer and aptamer-siRNA conjugates' development in our group for the treatment of HIV-1. Their potentials for targeted delivering RNAi therapeutics (eg, siRNA) and suppressing HIV-1 replication in vitro and in humanized animal model will be highlighted here. PMID- 25118116 TI - Comparison of low versus high (>40 mm Hg) pulse pressure to predict the benefit of cardiac resynchronization therapy for heart failure (from the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy Trial). AB - Low pulse pressure (PP) is associated with poor outcome in hospitalized patients with systolic heart failure (HF). However, the relation between PP and response to cardiac resynchronization therapy with defibrillator (CRT-D) is unknown. We aimed to evaluate the relation between preimplantation PP and echocardiographic response to CRT-D and subsequent clinical outcome after 1 year. The relation between preimplantation PP and echocardiographic response to CRT-D (defined as >15% reduction in left ventricular (LV) end-systolic volume at 1 year) was evaluated in 754 patients with CRT-D with left bundle branch block enrolled in Multicenter Automatic Defibrillator Cardioverter Defibrillator Implantation Trial Cardiac Resynchronization Therapy. The association between PP at 1 year and the risk for subsequent HF or death was evaluated using multivariate Cox model. Patients with high versus low PP (>40 vs <=40 mm Hg [lower quartile]) had a significantly greater reduction in LV end-systolic volume, LV end-diastolic volume, and LV dyssynchrony (p<0.01 for all comparisons). In multivariate analysis, the presence of high PP was associated with a 3.5-fold (p<0.001) increase in the likelihood of a positive echocardiographic response to CRT-D. Patients with high PP (>40 mm Hg, >lower quartile) 1 year after CRT-D implantation experienced a 50% reduction in the risk of subsequent HF or death (p=0.001) and 63% reduction in death only (p=0.001), compared with patients with low PP. In conclusion, high baseline PP is an independent predictor of echocardiographic response to CRT-D, and high PP after device implantation is associated with improved subsequent clinical outcome. PMID- 25118117 TI - Association of platelet-to-lymphocyte ratio with severity and complexity of coronary artery disease in patients with acute coronary syndromes. AB - The SYNTAX score (SXscore) is an anatomic scoring system based on coronary angiography (CA) that not only quantifies lesion severity and complexity but also predicts poor cardiovascular outcomes, including mortality, in patients with acute coronary syndromes (ACS). Recent studies have shown that platelet-to lymphocyte ratio (PLR) is associated with worse outcomes in many cardiovascular diseases. The aim of this study was to investigate the association of PLR with the severity and complexity of coronary atherosclerosis as assessed by the SXscore in patients with ACS who underwent urgent CA. A total of 1,016 patients with ACS who underwent urgent CA were included in the study from August 2012 to March 2014. Admission PLR values were calculated before CA was performed. The SXscore was determined from baseline CA. The patients were divided into 2 groups, those with low SXscores (<=22) and those with intermediate to high SXscores (>=23). PLRs were significantly higher in patients with intermediate to high SXscores compared with those with low SXscores (p<0.001). In-hospital mortality was significantly higher in the groups with high PLR and intermediate to high SXscores. In multivariate analysis, the independent predictors of intermediate to high SXscore were PLR (odds ratio 1.018, 95% confidence interval 1.013 to 1.023, p<0.001) together with the left ventricular ejection fraction (odds ratio 0.935, 95% confidence interval 0.910 to 0.960, p<0.001), and age (odds ratio 1.029, 95% confidence interval 1.029 to 1.054, p=0.02). A PLR>=116 had 71% sensitivity and 66% specificity in predicting intermediate to high SXscore. In conclusion, the PLR at admission is significantly associated with the severity and complexity of coronary atherosclerosis in patients with ACS. Increased PLR is an independent predictor of higher SXscore in patients with ACS who undergo urgent CA. PMID- 25118118 TI - Predictors of neurologic outcome in patients resuscitated from out-of-hospital cardiac arrest using classification and regression tree analysis. AB - The estimated survival rate of 8% to 10% after out-of-hospital cardiac arrest (OHCA) remains dismal. Few studies have addressed predictors of functional neurologic outcome after successful resuscitation. The objective of the study was to identify variables associated with favorable neurologic outcomes, defined by a Glasgow Coma Scale of 14 or 15, after OHCA. We used a propensity analysis and classification and regression tree model of 184 OHCA patients surviving to hospital admission at a cardiac arrest receiving center in Los Angeles County from 2008 to 2013. Forty-three patients (23%) had a favorable outcome, median age was 65 years (interquartile range [IQR] 54 to 76), and 98 (53%) were men. Sixty six patients (36%) presented with a shockable rhythm. The majority were witnessed, either by a civilian (n=115, 63%) or a paramedic (n=25, 14%). Bystander cardiopulmonary resuscitation was performed on 84 patients (46%); median dose of epinephrine was 2 mg (IQR 1 to 3). Median time to return of spontaneous circulation was 21 minutes (IQR 16 to 29); the median lactate level was 5.2 mmol/L (IQR 2.8 to 9.2). Lower epinephrine doses (<1.5 mg) and lactate levels<5 mmol/L were predictive of a normal Glasgow Coma Scale, with 90.7% sensitivity (95% confidence interval [CI] 76.9% to 96.9%), 47.5% specificity (95% CI 39.1% to 56.1%), a positive predictive value of 34.5% (95% CI 31.6% to 46.1%), a negative predictive value of 94.4% (95% CI 85.5% to 98.2%), and an area under the curve of 0.89. The propensity score-adjusted logistic regression model demonstrated that receiving <1.5 mg of epinephrine was associated with a favorable neurologic outcome (odds ratio 3.3, 95% CI 1.1 to 10, p=0.04). In conclusion, for patients surviving to hospital admission, a good neurologic outcome was associated with having received <1.5 mg of epinephrine and a lactate level<5 mmol/L. PMID- 25118119 TI - Comparison of the efficacy of pharmacoinvasive management for ST-segment elevation myocardial infarction in smokers versus non-smokers (from the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction). AB - Compared with non-smokers, cigarette smokers with ST-segment elevation myocardial infarctions derive greater benefit from fibrinolytic therapy. However, it is not known whether the optimal treatment strategy after fibrinolysis differs on the basis of smoking status. The Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) randomized patients with ST-segment elevation myocardial infarctions to a routine early invasive (pharmacoinvasive) versus a standard (early transfer only for rescue percutaneous coronary intervention or delayed angiography) strategy after fibrinolysis. The efficacy of these strategies was compared in 1,051 patients on the basis of their smoking status. Treatment heterogeneity was assessed between smokers and non-smokers, and multivariable analysis was performed to evaluate for an interaction between smoking status and treatment strategy after adjusting for baseline Global Registry of Acute Coronary Events (GRACE) risk score. Smokers (n=448) were younger, had fewer cardiovascular risk factors, and had lower GRACE risk scores. They had a lower rate of the primary composite end point of 30-day mortality, reinfarction, recurrent ischemia, heart failure, or cardiogenic shock and fewer deaths or reinfarctions at 6 months and 1 year. Smoking status was not a significant predictor of either primary or secondary end points in multivariable analysis. Pharmacoinvasive management reduced the primary end point compared with standard therapy in smokers (7.7% vs 13.6%, p=0.04) and non-smokers (13.1% vs 19.7%, p=0.03). Smoking status did not modify treatment effect on any measured outcomes (p>0.10 for all). In conclusion, compared with non-smokers, current smokers receiving either standard or early invasive management of ST segment elevation myocardial infarction after fibrinolysis have more favorable outcomes, which is likely attributable to their better baseline risk profile. The beneficial treatment effect of a pharmacoinvasive strategy is consistent in smokers and non-smokers. PMID- 25118120 TI - Treatment and outcomes of ST segment elevation myocardial infarction and out-of hospital cardiac arrest in a regionalized system of care based on presence or absence of initial shockable cardiac arrest rhythm. AB - The aim of this study was to evaluate the treatment and outcomes of patients with ST-segment elevation myocardial infarctions complicated by out-of-hospital cardiac arrest in a regional system of care. In this retrospective study, the effect of the absence of an initial shockable arrest rhythm was analyzed. The primary end point of survival with good neurologic outcome in patients with and without an initial shockable arrest rhythm was adjusted for age, witnessed arrest, bystander cardiopulmonary resuscitation, and treatment with therapeutic hypothermia and percutaneous coronary intervention. One-hundred sixty-eight of 348 patients (49%) survived to hospital discharge. Patients with a shockable initial rhythm were more likely to receive therapeutic hypothermia (48% vs 37%, risk ratio 1.2, 95% confidence interval [CI] 1.0 to 1.5) and to be treated in the cardiac catheterization laboratory (80% vs 43%, risk ratio 2.8, 95% CI 2.0 to 3.8). The likelihood of survival with good neurologic outcome in patients with a shockable initial rhythm compared with those presenting without a shockable rhythm was 4.8 (95% CI 2.7 to 8.7). In patients who underwent percutaneous coronary intervention, the likelihood of survival with good neurologic outcome was higher (risk ratio 2.7, 95% CI 1.1 to 6.8) in those with a shockable rhythm. In conclusion, the absence of an initial shockable rhythm in patients with ST segment elevation myocardial infarctions plus out-of-hospital cardiac arrest is associated with significantly worse survival and neurologic outcome. These differences persist despite application of therapies including therapeutic hypothermia and percutaneous coronary intervention within a regionalized system of care. PMID- 25118121 TI - Impact of pre-procedural cardiopulmonary instability in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial). AB - Rapid reperfusion with primary percutaneous coronary intervention improves survival in patients with ST-segment elevation myocardial infarction. Preprocedural cardiopulmonary instability and adverse events (IAE) may delay reperfusion time and worsen prognosis. The aim of this study was to evaluate the relation between preprocedural cardiopulmonary IAE, door-to-balloon time (DBT), and outcomes in the Harmonizing Outcomes With Revascularization and Stents in AMI (HORIZONS-AMI) trial. Preprocedural cardiopulmonary IAE included sustained ventricular or supraventricular tachycardia or fibrillation requiring cardioversion or defibrillation, heart block or bradycardia requiring pacemaker implantation, severe hypotension requiring vasopressors or intra-aortic balloon counterpulsation, respiratory failure requiring mechanical ventilation, and cardiopulmonary resuscitation. Three-year outcomes of patients with and without IAE according to DBT were compared. Among 3,602 patients, 159 (4.4%) had >=1 IAE. DBT did not differ significantly in patients with and without IAE; however, patients with IAE were less likely to have Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow after percutaneous coronary intervention. Mortality at 3 years was significantly higher in patients with versus those without IAE (17.0% vs 6.3%, p<0.0001), and IAE was an independent predictor of mortality, whereas DBT was not. However, a significant interaction was present such that 3-year mortality was reduced in patients with DBT<99 minutes (the median) versus >=99 minutes to a greater extent in patients with IAE (9.9% vs 20.7%, hazard ratio 0.43, 95% confidence interval 0.16 to 1.16) compared with those without IAE (5.0% vs 7.2%, hazard ratio 0.69, 95% confidence interval 0.50 to 0.95) (p for interaction=0.004). In conclusion, IAE before PCI is an independent predictor of death and identifies a high-risk group in whom faster reperfusion may be particularly important to improve survival. PMID- 25118122 TI - Meta-analysis of left ventricular hypertrophy and sustained arrhythmias. AB - Presence of left ventricular hypertrophy (LVH) has been reported to be associated with supraventricular and ventricular arrhythmias, but the association has not been systematically quantified and evaluated. A systematic search of studies in MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases was undertaken through April 2014. Studies reporting on LVH and sustained arrhythmias such as atrial fibrillation and supraventricular tachycardias (SVTs) and ventricular arrhythmias (tachycardia and fibrillation) were identified. Pooled effect estimates were calculated with random-effects models (DerSimonian and Laird). A total of 10 eligible studies with 27,141 patients were included in the analysis. The incidence of SVT in patients with LVH was 11.1% compared with 1.1% among patients without LVH (p<0.001). Patients with LVH had 3.4-fold greater odds of developing SVT (odds ratio 3.39, 95% confidence interval 1.57 to 7.31) than those without LVH, although significant heterogeneity was present (I2=98%). Meta-regression analyses revealed the heterogeneity to have originated from differences in the baseline covariates such as age, male gender, hypertension, and diabetes of the individual studies. The incidence of ventricular arrhythmias was 5.5% compared with 1.2% in patients without LVH (p<0.001). The occurrence of ventricular tachycardia or fibrillation was 2.8-fold greater, in the presence of LVH (odds ratio 2.83, 95% confidence interval 1.78 to 4.51), and there was no significant heterogeneity (I2=9%). Presence of LVH in hypertensive patients is associated with a greater risk of sustained supraventricular/atrial and ventricular arrhythmias, and there is an unmet need for identifying and refining risk stratification for this group. PMID- 25118123 TI - Outcomes of patients with ischemic mitral regurgitation undergoing percutaneous coronary intervention. AB - Ischemic mitral regurgitation (IMR) is associated with poor outcomes in patients with coronary artery disease. The impact of percutaneous coronary intervention (PCI) on patients with IMR is not well elucidated. We sought to determine the outcomes of patients with severe IMR who underwent PCI. Patients with severe (>=3+) IMR who underwent PCI from 1998 to 2010 were identified. Improvement in IMR was defined as reduction in severity from >=3+ to <=2+ without any other invasive intervention beyond PCI. Outcomes were compared between patients with and without improvement in IMR after PCI. One hundred thirty-seven patients with severe IMR were included in our study. After PCI, 50 patients (36.5%) had improvement in IMR with PCI alone and 24 patients (18.5%) required another intervention. Left atrial size was a significant predictor of improvement in IMR (odds ratio 0.39, 95% confidence interval 0.2 to 0.8). Left ventricular size decreased (systolic diameter 3.9+/-0.3 vs 4.6+/-0.2 cm, p=0.0008 and diastolic diameter 5.2+/-0.2 vs 5.7+/-0.2 cm, p=0.002) and ejection fraction increased (39.1+/-4.0% vs 33.1+/-1.9%, p=0.002) significantly after PCI in the patients with improvement in IMR compared with patients without improvement. Patients with improvement in IMR had numerically better survival; however, it was not statistically significant (p log-rank=0.2). In conclusion, 1/3 of the patients with IMR had improvement in severity of IMR with PCI alone. Improvement in IMR was associated with left ventricular reverse remodeling. Left atrial size was an important predictor of improvement in IMR after PCI. PMID- 25118124 TI - Rate of percutaneous coronary intervention for the management of acute coronary syndromes and stable coronary artery disease in the United States (2007 to 2011). AB - Although the benefit of percutaneous coronary interventions (PCIs) for patients presenting with acute coronary syndromes (ACS) has been established in numerous studies, the role of PCI in stable coronary artery disease (CAD) remains controversial. With the publication of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluations trial and the appropriate use criteria for coronary artery revascularization, we sought to examine the impact of these treatment strategies and guidelines on the current practice of PCI in United States. We conducted a serial cross-sectional study with time trends of patients undergoing PCI for ACS and stable CAD from 2007 to 2011. The annual rate of all PCI decreased by 27.7% from 10,785 procedures per million adults per year in 2007 to 2008 to 7,801 procedures per million adults per year in 2010 to 2011 (p=0.03). Although there was no statistically significant decrease in the PCI utilization for ACS from 2007 to 2011, PCI utilization for stable CAD decreased by 51.7% (from 2,056 procedures per million adults per year in 2008 to 992 procedures per million adults per year in 2011, p=0.02). Hospitals with a higher volume of PCI experienced a more significant decrease. Decrease in PCI utilization for stable CAD was statistically significant for patients with Medicare and private insurance/health maintenance organization (44.5%, p=0.03 and 59.5%, p=0.007, respectively). In conclusion, the rate of PCI decreased substantially starting from 2009 in the United States. Most of the decrease was attributed to the reduction in PCI utilization for stable CAD. PMID- 25118125 TI - Bipolar disorder and its relation to major psychiatric disorders: a family-based study in the Swedish population. AB - OBJECTIVES: Bipolar disorder (BPD) shares genetic components with other psychiatric disorders; however, uncertainty remains about where in the psychiatric spectra BPD falls. To understand the etiology of BPD, we studied the familial aggregation of BPD and co-aggregation between BPD and schizophrenia, depression, anxiety disorders, attention-deficit hyperactivity disorder, drug abuse, personality disorders, and autism spectrum disorders. METHODS: A population-based cohort was created by linking several Swedish national registers. A total of 54,723 individuals with BPD were identified among 8,141,033 offspring from 4,149,748 nuclear families. The relative risk of BPD in relatives and the co-occurrence of other psychiatric disorders in patients with BPD and their relatives were compared to those of matched-population controls. Structural equation modeling was used to estimate the heritability and tetrachoric correlation. RESULTS: The familial risks for relatives of BPD probands were 5.8 7.9 in first-degree relatives, and decreased with genetic distance. Co-occurrence risks for other psychiatric disorders were 9.7-22.9 in individuals with BPD and 1.7-2.8 in full siblings of BPD probands. Heritability for BPD was estimated at 58%. The correlations between BPD and other psychiatric disorders were considerable (0.37-0.62) and primarily due to genetic effects. The correlation with depression was the highest (0.62), and was 0.44 for schizophrenia. CONCLUSIONS: The high familial risks provide evidence that genetic factors play an important role in the etiology of BPD, and the shared genetic determinants suggest pleiotropic effects across different psychiatric disorders. Results also indicate that BPD is in both the mood and psychotic spectra, but possibly more closely related to mood disorders. PMID- 25118126 TI - The effect of different delineator post configurations on driver speed in night time traffic: a driving simulator study. AB - The aim of the study was to investigate how different delineator post configurations affect driver speed in night-time traffic. In addition, the potential speed effect of introducing a secondary task was investigated. The study was carried out in a car simulator on a road stretch including straight road sections as well as curves with different radii. Fourteen drivers participated in the study and the results show that absence of delineator posts leads to reduced speed. However, provided that there are delineator posts continuously present along the road, the overall driver speed is basically the same, regardless of the spacing between the delineator posts. The results also imply that to reduce driver speed in curves with small radius, using more compact spacing of posts in these curves as compared to in curves with a larger radius, could be a potential strategy. Additionally, the speed reducing effect of a secondary task was only prevailing where the task was initiated. PMID- 25118127 TI - Why do organizations not learn from incidents? Bottlenecks, causes and conditions for a failure to effectively learn. AB - If organizations would be able to learn more effectively from incidents that occurred in the past, future incidents and consequential injury or damage can be prevented. To improve learning from incidents, this study aimed to identify limiting factors, i.e. the causes of the failure to effectively learn. In seven organizations focus groups were held to discuss factors that according to employees contributed to the failure to learn. By use of a model of the learning from incidents process, the steps, where difficulties for learning arose, became visible, and the causes for these difficulties could be studied. Difficulties were identified in multiple steps of the learning process, but most difficulties became visible when planning actions, which is the phase that bridges the gap from incident investigation to actions for improvement. The main causes for learning difficulties, which were identified by the participants in this study, were tightly related to the learning process, but some indirect causes - or conditions - such as lack of ownership and limitations in expertise were also mentioned. The results illustrate that there are two types of causes for the failure to effectively learn: direct causes and indirect causes, here called conditions. By actively and systematically studying learning, more conditions might be identified and indicators for a successful learning process may be determined. Studying the learning process does, however, require a shift from learning from incidents to learning to learn. PMID- 25118128 TI - Causes of fatal accidents for instrument-certified and non-certified private pilots. AB - Instrument certification (IFR) enhances a pilot's skills in precisely controlling the aircraft and requires a higher level of standards in maintaining heading and altitude compared with the less stringent private pilot certificate. However, there have been no prior studies to compare fatal accident causes for airmen with, and without, this rating, The NTSB accident database was queried for general aviation fatal accidents for private pilots with, and without IFR certification. Exact Poisson tests were used to calculate whether two rate parameters were equal (ratio of 1), normalized to the number of IFR-rated pilots and flight hours in the given time period. Proportion tests were used to determine whether there were significant differences in fatal accident causes between IFR-certified and non-certified pilots. A logistic regression for log odds success was used in determining the trend and effect of age on fatal accident rates. IFR certification was associated with a reduced risk of accidents due to failure to maintain obstacle/terrain clearance and spatial disorientation for day and night operations respectively. In contrast, the likelihood of fatal accident due to equipment malfunction during day operations was higher for IFR certified pilots. The fatal accident rate decreased over the last decade for IFR certified but not for non-IFR-certified private pilots. However, the overall accident rate for IFR-certified private pilots was more than double that of the cohort lacking this certification. Finally, we found a trend for an increased fatality rate with advancing age for both group of pilots. Our findings informs on where training and/or technology should be focused. Both training for aerodynamic stalls, which causes over a quarter of all fatal accidents, should be intensified for both IFR-certified and non-certified private pilots. Similarly, adherence to minimum safe altitudes for both groups of pilots should be encouraged toward reducing the fatal accidents rate due to failure to maintain obstacle/terrain clearance. For night operations, the high percentage of accidents due to spatial disorientation for non-IFR certified airmen suggests that additional training be required for such operations or such flights carry restrictions for this subset of pilots. PMID- 25118129 TI - Multifamily psychoeducation for improvement of mental health among relatives of patients with major depressive disorder lasting more than one year: study protocol for a randomized controlled trial. AB - BACKGROUND: Major depressive disorder (MDD) is a long-lasting disorder with frequent relapses that have significant effects on the patient's family. Family psychoeducation is recognized as part of the optimal treatment for patients with psychotic disorder. A previous randomized controlled trial has found that family psychoeducation is effective in enhancing the treatment of MDD. Although MDD can easily become a chronic illness, there has been no intervention study on the families of patients with chronic depression. In the present study, we design a randomized controlled trial to examine the effectiveness of family psychoeducation in improving the mental health of relatives of patients with MDD lasting more than one year. METHODS/DESIGN: Participants are patients with MDD lasting more than one year and their relatives. Individually randomized, parallel group trial design will be employed. Participants will be allocated to one of two treatment conditions: relatives will receive (a) family psychoeducation (four, two-hour biweekly multifamily psychoeducation sessions) plus treatment-as-usual for the patient (consultation by physicians), or (b) counseling for the family (one counseling session from a nurse) plus treatment-as-usual for the patient. The primary outcome measure will be relatives' mental health as measured by K6 that was developed to screen for DSM-IV depressive and anxiety disorder. Additionally, the severity of depressive symptoms in patients measured by the Beck Depression Inventory-II (BDI-II) scale will be assessed. Data from the intention-to-treat sample will be analyzed 16 weeks after randomization. DISCUSSION: This is the first study to evaluate the effectiveness of family psychoeducation for relatives of patients with MDD lasting more than one year. If this type of intervention is effective, it could be a new method of rehabilitation for patients with MDD lasting more than one year. TRIAL REGISTRATION: Clinical Trials.gov NCT01734291 (registration date: 18 October 2012). PMID- 25118135 TI - Whole-of-society approach for public health policymaking: a case study of polycentric governance from Quebec, Canada. AB - In adopting a whole-of-society (WoS) approach that engages multiple stakeholders in public health policies across contexts, the authors propose that effective governance presents a challenge. The purpose of this paper is to highlight a case for how polycentric governance underlying the WoS approach is already functioning, while outlining an agenda to enable adaptive learning for improving such governance processes. Drawing upon a case study from Quebec, Canada, we employ empirically developed concepts from extensive, decades-long work of the 2009 Nobel laureate Elinor Ostrom in the governance of policy in nonhealth domains to analyze early efforts at polycentric governance in policies around overnutrition, highlighting interactions between international, domestic, state and nonstate actors and processes. Using information from primary and secondary sources, we analyze the emergence of the broader policy context of Quebec's public health system in the 20th century. We present a microsituational analysis of the WoS approach for Quebec's 21st century policies on healthy lifestyles, emphasizing the role of governance at the community level. We argue for rethinking prescriptive policy analysis of the 20th century, proposing an agenda for diagnostic policy analysis, which explicates the multiple sets of actors and interacting variables shaping polycentric governance for operationalizing the WoS approach to policymaking in specific contexts. PMID- 25118134 TI - Distribution of perfluoroalkyl compounds in rats: Indication for using hair as bioindicator of exposure. AB - Hair analysis is potentially advantageous in exposure assessment of perfluoroalkyl acids (PFAAs) as a non-invasive method, combined with the ability to reflect long-term exposure. The present study aims to assess the feasibility of using hair as an indicator of PFAA exposure. Adult male and female rats were subchronically exposed to selected PFAAs, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonate (PFOS), for 90 days. Hair, serum, and other tissues, including liver, kidney, spleen, lung, brain and heart, as well as the urine and feces excretions, were analyzed for PFAA levels. PFOA/PFNA/PFOS were detected in rat hair in a dose-dependent manner, in the order of PFOS>PFNA>PFOA. Hair PFAA concentrations were higher in male rats than the female rats, except for PFOS at low dose. Moreover, significant positive correlations as well as similar PFAA profiles were observed between hair, serum, and other tissues. Besides, hair PFAAs were negatively correlated with the urinary excretion rate. Although the influencing factors in humans still need further investigation, the results suggested that hair is capable of reflecting PFAA exposure, and could be employed as an alternative exposure bioindicator of PFAAs. PMID- 25118136 TI - Towards large scale fermentative production of succinic acid. AB - Fermentative production of succinic acid (SA) from renewable carbohydrate feed stocks can have the economic and sustainability potential to replace petroleum based production in the future, not only for existing markets, but also new larger volume markets. To accomplish this, extensive efforts have been undertaken in the field of strain construction and metabolic engineering to optimize SA production in the last decade. However, relatively little effort has been put into fermentation process development. The choice for a specific host organism determines to a large extent the process configuration, which in turn influences the environmental impact of the overall process. In the last five years, considerable progress has been achieved towards commercialization of fermentative production of SA. Several companies have demonstrated their confidence about the economic feasibility of fermentative SA production by transferring their processes from pilot to production scale. PMID- 25118137 TI - Mammalian cell-produced therapeutic proteins: heterogeneity derived from protein degradation. AB - Therapeutic glycoproteins, for example, antibodies (Abs) and Fc fusion proteins when produced in mammalian cells, such as Chinese hamster ovary (CHO) cells generally exhibit heterogeneity. Both the oligosaccharide moiety and the protein moiety contribute to this phenomenon. Non-enzymatic and enzymatic pathways of protein fragmentation generate heterogeneity in the polypeptide backbone. In the non-enzymatic pathway, physical and chemical events such as light, oxidation, and others can cause the protein moiety to become unstable leading to its fragmentation. Intracellular and secreted proteases are involved in the enzymatic degradation of proteins. This degradative process is modulated by the oligosaccharide moiety of the glycoprotein as well as glycosidases, including sialidases that are secreted in the culture medium. This review focuses on the factors that modulate heterogeneity of the protein moiety especially by the enzymatic methods. Availability of the CHO genome database will facilitate the development of host cell lines with minimal degradative properties. PMID- 25118138 TI - Placental lipases in pregnancies complicated by gestational diabetes mellitus (GDM). AB - Infants of women with gestational diabetes mellitus (GDM) are more likely to be born large for gestational age with a higher percentage body fat. Elevated maternal lipids may contribute to this. Placental lipases such as lipoprotein lipase (LPL), endothelial lipase (EL) and hormone sensitive lipase (HSL) are involved in transferring lipids from mother to fetus. Previous studies of expression of these lipases in placentae in women with diabetes in pregnancy have reported divergent results. Intracellular lipases such as adipose triglyceride lipase (ATGL), and HSL are central to lipid droplet metabolism. The activities of these lipases are both influenced by Perilipin 1, and ATGL is also activated by a co-factor comparative gene identification-58 (CGI-58) and inhibited by G0/G1 switch gene 2 (GS02). None of these modifying factors or ATGL have been examined previously in placenta. The purpose of this study was therefore to examine the expression of ATGL, HSL, LPL, EL, as well as Perilipin 1, GS02 and CGI-58 in term pregnancies complicated by GDM. mRNA and protein expression of the lipases were measured in placentae from 17 women with GDM and 17 normoglycaemic pregnancies, matched for maternal BMI and gestational age of delivery. ATGL mRNA expression was increased and HSL mRNA expression reduced in placentae from GDM although there was no differences in protein expression of any of the lipases. All lipases were localised to trophoblasts and endothelial cells. The expression of Perilipin 1 and CGI-58 mRNA was increased and GS02 not altered in GDM. These results suggest that there is no difference in expression in these four lipases between GDM and normoglycaemic placentae, and therefore altered lipid transfer via these lipases does not contribute to large for gestational age in infants of women with GDM. PMID- 25118139 TI - Use of psychotherapy in a representative adult community sample in Sao Paulo, Brazil. AB - Little is known about the use of psychotherapy to treat common mental disorders in a major city in a middle-income country. Our data come from in-home interviews with a stratified random sample of 2000 community residents aged 18 to 65 years in the city of Sao Paulo, Brazil. The information obtained included sociodemographic characteristics; psychotropic drugs; mental status; and lifetime, previous 12 months, and current use of psychotherapy. Logistic regression was used to examine determinants of use of psychotherapy. Of the sample, 22.7% met General Health Questionnaire-12 criteria for common mental disorders. Lifetime, previous 12 months, and current use of psychotherapy were reported by 14.6%, 4.6%, and 2.3% of the sample, respectively. Users typically were women, were more educated, had higher income, were not married, were unemployed, and had common mental disorders. Further analysis found that 47% (with higher education and income) paid out-of-pocket, and 53% used psychotropic medication. Psychotherapy does not seem to be the preferred treatment of common mental disorders. PMID- 25118140 TI - Elevated levels of urinary markers of oxidatively generated DNA and RNA damage in bipolar disorder. AB - OBJECTIVES: The pathophysiological mechanisms underlying bipolar disorder and its multi-system nature are unclear. Oxidatively generated damage to nucleosides has been demonstrated in metabolic disorders; however, the extent to which this occurs in bipolar disorder in vivo is unknown. We investigated oxidatively generated damage to DNA and RNA in patients with bipolar disorder and its relationship with the affective phase compared with healthy control subjects. METHODS: Urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8 oxo-7,8-dihydroguanosine (8-oxoGuo), markers of oxidatively generated DNA and RNA damage, respectively, was measured in 37 rapid cycling patients with bipolar disorder and in 40 age- and gender-matched healthy control subjects. Employing a longitudinal design, repeated measurements of both markers were evaluated in various affective phases in patients with bipolar disorder during a six- to 12 month period and compared with repeated measurements in healthy control subjects. RESULTS: In linear mixed models, adjusting for demographical, metabolic, and lifestyle factors, the excretion of 8-oxodG and 8-oxoGuo was significantly elevated in euthymic patients with bipolar disorder compared with healthy control subjects, with increases of 40% (p < 0.0005) and 43% (p < 0.0005), respectively. The increased oxidatively generated nucleoside damage was present through all affective phases of the illness, with no significant difference between affective states. CONCLUSIONS: Our results indicate that bipolar disorder is associated with increased oxidatively generated damage to nucleosides. The findings could suggest a role for oxidatively generated damage to DNA and RNA as a molecular mechanism contributing to the increased risk of medical disorders, shortened life expectancy, and the progressive course of illness observed in bipolar disorder. PMID- 25118147 TI - Mediterranean Diet and Cardiovascular Risk: Beyond Traditional Risk Factors. AB - A strict adherence to the Mediterranean Diet (MedDiet) has repeatedly been linked to a low risk of cardiovascular disease in several situations. Initially, the mechanisms considered as possible causes of this were based on the effects of this dietary pattern on the so-called traditional risk factors (especially lipids and blood pressure). However, the high relative reduction in the prevalence of cardiovascular morbidity and mortality were not proportional to the limited findings about regulation of those traditional risk factors. In addition to several studies confirming the above effects, current research on the MedDiet is being focused on defining its effects on non-traditional risk factors, such as endothelial function, inflammation, oxidative stress, or on controlling the conditions which predispose people to cardiovascular events, such as obesity, metabolic syndrome or type 2 diabetes mellitus. In the current article, after briefly reviewing the known effects of the MedDiet on the traditional risk factors, we will mainly focus on reviewing the current evidence about the effects that this dietary pattern exerts on alternative factors, including postprandial lipemia or coagulation, among others, as well as providing a short review on future directions. PMID- 25118148 TI - The importance of dietary protein for muscle health in inactive, hospitalized older adults. AB - Dietary protein and amino acids are necessary for overall human health. Insufficient protein intake induces a negative protein balance with adverse outcomes such as muscle atrophy and functional decline--outcomes that are worsened in older adults. Furthermore, during inactivity, such as bed rest/hospitalization, skeletal muscle protein synthesis is reduced, protein balance is negative, and older adults lose significant amounts of muscle. Dietary protein and amino acid supplementation (~ 30 g protein and ~ 3 g leucine) stimulate skeletal muscle protein anabolism in healthy, community-dwelling older adults and may be considered as possible nutritional interventions to improve the muscle protein balance and potentially support skeletal muscle maintenance in hospitalized older adults. The following is a timely review of metabolic and dietary challenges faced by hospitalized older adults and potential dietary protein and amino acids solutions for maintaining skeletal muscle health during hospitalization-induced inactivity in this population. PMID- 25118146 TI - Effect of guided self-determination youth intervention integrated into outpatient visits versus treatment as usual on glycemic control and life skills: a randomized clinical trial in adolescents with type 1 diabetes. AB - BACKGROUND: Providing care for adolescents with type 1 diabetes is complex, demanding, and often unsuccessful. Guided self-determination (GSD) is a life skills approach that has been proven effective in caring for adults with type 1 diabetes. To improve care, GSD was revised for adolescents, their parents, and interdisciplinary healthcare providers (HCP) to create GSD-Youth (GSD-Y). We evaluated the impact of GSD-Y after it was integrated into pediatric outpatient visits versus treatment-as-usual, focusing on glycemic control and the development of life skills in adolescents with type 1 diabetes. METHODS: Seventy one adolescents (mean age: 15 years, mean duration of diabetes: 5.7 years, mean HbA1c: 77 mmol/mol (9.1%), upon entering the study) from two pediatric departments were randomized into a GSD-Y group (n = 37, GSD-Y was provided during individual outpatient sessions) versus a treatment-as-usual group (n = 34). The primary outcome was the HbA1c measurement. The secondary outcomes were life skills development (assessed by self-reported psychometric scales), self monitored blood glucose levels, and hypo- and hyperglycemic episodes. The analysis followed an intention-to-treat basis. RESULTS: Fifty-seven adolescents (80%) completed the trial, and 53 (75%) completed a six-month post-treatment follow-up. No significant effect of GSD-Y on the HbA1c could be detected in a mixed-model analysis after adjusting for the baseline HbA1c levels and the identity of the HCP (P = 0.85). GSD-Y significantly reduced the amotivation for diabetes self-management after adjusting for the baseline value (P = 0.001). Compared with the control group, the trial completion was prolonged in the GSD-Y group (P <0.001), requiring more visits (P = 0.05) with a higher rate of non attendance (P = 0.01). GSD-Y parents participated in fewer of the adolescents' visits (P = 0.05) compared with control parents. CONCLUSIONS: Compared with treatment-as-usual, GSD-Y did not improve HbA1c levels, but it did decrease adolescents' amotivation for diabetes self-management. TRIAL REGISTRATION: ISRCTN 54243636, registered on 10 January 2010. Life skills for adolescents with type 1 diabetes and their parents. PMID- 25118149 TI - Effect of operating conditions on yield and quality of biocrude during hydrothermal liquefaction of halophytic microalga Tetraselmis sp. AB - The biomass of halophytic microalga Tetraselmis sp. with 16%w/w solids was converted into biocrude by a hydrothermal liquefaction (HTL) process in a batch reactor at different temperatures (310, 330, 350 and 370 degrees C) and reaction times (5, 15, 30, 45 and 60min). The biocrude yield, elemental composition, energy density and severity parameter obtained at various reaction conditions were used to predict the optimum condition for maximum recovery of biocrude with improved quality. This study clearly indicated that the operating condition for obtaining maximum biocrude yield and ideal quality biocrude for refining were different. A maximum biocrude yield of ~65wt% ash free dry weight (AFDW) was obtained at 350 degrees C and 5min, with a severity parameter and energy density of 5.21 and ~35MJ/kg, respectively. The treatment with 45min reaction time recorded ~62wt% (AFDW) yield of biocrude with and energy density of ~39MJ/kg and higher severity parameter of 7.53. PMID- 25118150 TI - Phosphorus elimination from aqueous solution using 'zirconium loaded okara' as a biosorbent. AB - This work deals with the capture of phosphorus from aqueous solutions by biosorption onto zirconium loaded okara (ZLO). The batch-mode experiments were conducted to examine the effect of pH, biosorbent dose, initial phosphorus concentration, contact time, and temperature on the process. It was found that, the adsorption was most favored in the pH range of 2-6. The optimal doses for the adsorption, at initial phosphorus concentrations of 5, 10, 25, 50mg/L were 2, 3, 7, 10g/L, respectively. The maximum adsorption capacity of ZLO was approximately 44.13mg PO4/g at 298K. The phosphate removal was rapid, reaching 95% in 30min. Freundlich model best fitted the equilibrium data, while Pseudo-second order model satisfactorily described the kinetic results. Thermodynamic analysis revealed feasible, spontaneous, and endothermic nature of the process. The research would be beneficial for developing a promising, eco-friendly phosphorus biosorbent from a plentiful AWB - okara. PMID- 25118151 TI - Enhanced pathway efficiency of Saccharomyces cerevisiae by introducing thermo tolerant devices. AB - In this study, thermo-tolerant devices consisting of heat shock genes from thermophiles were designed and introduced into Saccharomyces cerevisiae for improving its thermo-tolerance. Among ten engineered thermo-tolerant yeasts, T.te TTE2469, T.te-GroS2 and T.te-IbpA displayed over 25% increased cell density and 1.5-4-fold cell viability compared with the control. Physiological characteristics of thermo-tolerant strains revealed that better cell wall integrity, higher trehalose content and enhanced metabolic energy were preserved by thermo-tolerant devices. Engineered thermo-tolerant strain was used to investigate the impact of thermo-tolerant device on pathway efficiency by introducing beta-amyrin synthesis pathway, showed 28.1% increased beta-amyrin titer, 28-35 degrees C broadened growth temperature range and 72h shortened fermentation period. The results indicated that implanting heat shock proteins from thermophiles to S. cerevisiae would be an efficient approach to improve its thermo-tolerance. PMID- 25118154 TI - Are trials with nursing interventions pragmatic? PMID- 25118152 TI - Effects of earthworms on physicochemical properties and microbial profiles during vermicomposting of fresh fruit and vegetable wastes. AB - This study aimed to investigate the effect of earthworms on physicochemical and microbial properties during vermicomposting of fresh fruit and vegetable wastes (FVW) by contrasting two decomposing systems of FVW with and without earthworms for 5weeks. Compared to control treatment (without earthworms), vermicomposting treatment resulted in a rapid decrease of electrical conductivity and losses of total carbon and nitrogen from the 2nd week. Quantitative PCR displayed that earthworms markedly enhanced bacterial and fungal densities, showing the higher values than control, during the whole decomposition process. In addition, denaturing gradient gel electrophoresis combined with sequencing analysis revealed that earthworms pronouncedly modified bacterial and fungal community structures, through broadening the community diversities of Actinobacteria, Bacteroidetes, Proteobacteria, and Ascomycotina. These results suggest that the presence of earthworms promoted the activity and population of bacteria and fungi, and modified their communities, thus altering the decomposition pathway of fresh FVW. PMID- 25118155 TI - Nonlinear dynamics of mood regulation in bipolar disorder. AB - OBJECTIVES: We sought to study the underlying dynamic processes involved in mood regulation in subjects with bipolar disorder and healthy control subjects using time-series analysis and to then analyze the relation between anxiety and mood using cross-correlation techniques. METHODS: We recruited 30 healthy controls and 30 euthymic patients with bipolar disorder. Participants rated their mood, anxiety, and energy levels using a paper-based visual analog scale; and they also recorded their sleep and any life events. Information on these variables was provided over a three-month period on a daily basis, twice per day. We analyzed the data using Box-Jenkins time series analysis to obtain information on the autocorrelation of the series (for mood) and cross-correlation (mood and anxiety series). RESULTS: Throughout the study, we analyzed 10,170 data points. Self ratings for mood, anxiety, and energy were normally distributed in both groups. Autocorrelation functions for mood in both groups were governed by the autoregressive integrated moving average (ARIMA) (1,1,0) model, which means that current values in the series were related to one previous point only. We also found a negative cross-correlation between mood and anxiety. CONCLUSIONS: Mood can be considered a memory stochastic process; it is a flexible, dynamic process that has a 'short memory' both in healthy controls and euthymic patients with bipolar disorder. This process may be quite different in untreated patients or in those acutely ill. Our results suggest that nonlinear measures can be applied to the study of mood disorders. PMID- 25118156 TI - Feasibility of a randomized controlled trial of functional strength training for people between six months and five years after stroke: FeSTivaLS trial. AB - BACKGROUND: Functional Strength Training (FST) could enhance recovery late after stroke. The aim of this study was to evaluate the feasibility of a subsequent fully powered, randomized controlled trial. METHODS: The study was designed as a randomized, observer-blind trial. Both interventions were provided for up to one hour a day, four days a week, for six weeks. Evaluation points were before randomization (baseline), after six weeks intervention (outcome), and six weeks thereafter (follow-up). The study took place in participants' own homes. Participants (n = 52) were a mean of 24.4 months after stroke with a mean age of 68.3 years with 67.3% male. All had difficulty using their paretic upper (UL) and lower limb (LL). Participants were allocated to FST-UL or FST-LL by an independent randomization service. The outcome measures were recruitment rate, attrition rate, practicality of recruitment strategies, occurrence of adverse reactions, acceptability of FST, and estimation of sample size for a subsequent trial. Primary clinical efficacy outcomes were the Action Research Arm Test (ARAT) and the Functional Ambulation Categories (FAC). Analysis was conducted using descriptive statistics and thematic analysis of participants' views of FST. A power calculation used estimates of clinical efficacy variance to estimate sample size for a subsequent trial. RESULTS: The screening process identified 1,127 stroke survivors of whom 52 (4.6%) were recruited. The recruitment rate was higher for referral from community therapists than for systematic identification of people discharged from an acute stroke unit. The attrition rate was 15.5% at the outcome and follow-up time-points. None of the participants experienced an adverse reaction. The participants who remained in the study at outcome had received 68% of the total possible amount of therapy. Participants reported that their experience of FST provided a sense of purpose and involvement and increased their confidence in performing activities. The power calculation provides estimation that 150 participants in each group will be required for a subsequent clinical trial. CONCLUSIONS: This study found that a subsequent clinical trial was feasible with modifications to the recruitment strategy to be used. TRIAL REGISTRATION: Controlled-trials.com ISCTN71632550, 30 January 2009. PMID- 25118159 TI - Co-inheritance of alpha-thalassaemia and beta-thalassaemia in a prenatal screening population in mainland China. AB - OBJECTIVE: To determine the prevalence of alpha-thalassaemia in beta-thalassaemia individuals in a Chinese population. METHODS: The standard diagnostic marker for beta-thalassaemia was elevation of the Hb A2 level (>3.5%) with low mean corpuscular volume. The common alpha-thalassaemia mutations were studied by molecular analysis in all identified beta-thalassaemia carriers. RESULTS: A prevalence rate of 3.3% for beta-thalassaemia was found in our population; alpha- and beta-thalassaemia interactions were found to co-exist in 17.8% of the beta thalassaemia carriers. The -SEA deletion was the most common alpha-thalassaemia mutation co-inherited with beta-thalassaemia, followed by the -alpha3.7 deletion, the -alpha4.2 deletion, Hb Quong Sze, and Hb Constant Spring. CONCLUSION: Our results suggest that it could be valuable to study co-existing alpha-globin mutations in subjects with beta-thalassaemia trait in a prenatal screening programme, especially in populations with a high prevalence of haemoglobinopathies. PMID- 25118157 TI - Toll-like receptor 3 activation is required for normal skin barrier repair following UV damage. AB - UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic keratinocytes that activates Toll-like receptor 3 (TLR3). This release of ncRNA triggers inflammation in the skin following UV damage. Recently, TLR3 activation was also shown to aid wound repair and increase the expression of genes associated with permeability barrier repair. Here, we sought to test whether skin barrier repair after UVB damage is dependent on the activation of TLR3. We observed that multiple ncRNAs induced expression of skin barrier repair genes, that the TLR3 ligand Poly (I:C) also induced expression and function of tight junctions, and that the ncRNA U1 acts in a TLR3-dependent manner to induce expression of skin barrier repair genes. These observations were shown to have functional relevance as Tlr3-/- mice displayed a delay in skin barrier repair following UVB damage. Combined, these data further validate the conclusion that recognition of endogenous RNA by TLR3 is an important step in the program of skin barrier repair. PMID- 25118158 TI - Identifying a polymorphic 'switch' that influences miRNAs' regulation of a myasthenia gravis risk pathway. AB - The significant roles of genetic variants in myasthenia gravis (MG) pathogenesis have been demonstrated in many studies, and recently it has been revealed that aberrant level/regulation of microRNAs (miRNAs) might contribute to the initiation and progression of MG. However, the dysfunction of miRNA associated with single nucleotide polymorphisms (miRSNPs) has not been well investigated in MG. In this study, we created a contemporary catalog of 89 MG risk genes via manual literature-mining. Based on this risk gene catalog, we obtained 18 MG risk pathways. Furthermore, we identified 93 miRNAs that target MG risk pathways and revealed the miRSNPs 'switches' in miRNA regulation in the MG risk pathways by integrating the database information of miRSNPs. We also constructed a miRNA mediated SNP switching pathway network (MSSPN) to intuitively analyze miRNA regulation of MG risk pathways and the relationship of the polymorphism 'switch' with these changes in regulation. Moreover, we carried out in-depth dissection on the correlation between hsa05200 (pathway in cancer) and MG development, and elaborated the significance of 4 high-risk genes. By network analysis and literature mining, we proposed a potential mechanism of miRSNPs->gene->pathway effects on MG pathogenesis, especially for rs28457673 (miR-15/16/195/424/497 family)->IGF1R->hsa05200 (pathway in cancer). Therefore, our studies have revealed a functional role for genetic modulators in MG pathogenesis at a systemic level, which could be informative for further miRNA and miRSNPs studies in MG. PMID- 25118161 TI - Academic vascular unit collaboration with advertising agency yields higher compliance in screening for abdominal aortic aneurysm. AB - To improve compliance with abdominal aortic aneurysm (AAA) screening in low compliance areas, individually tailored invitations were developed in collaboration with a professional advertising agency. Compliance increased in two intervention municipalities from 71.4% in 2010-2012 to 78.1% in 2013 (p = 0.025), and was then higher [odds ratio 1.7; 95% confidence interval 1.1-2.6; p = 0.013] than in two control municipalities in which compliance was unchanged (417/552 [75.5%] in 2010-12 and 122/180 [67.8%] in 2013). Compliance with AAA-screening can be increased by collaboration with a professional advertising agency, albeit at a comparably high cost. PMID- 25118162 TI - Axillary burden of disease following false-negative preoperative axillary evaluation. AB - BACKGROUND: Preoperative axillary ultrasound (AUS) and fine-needle aspiration (FNA) are sensitive and specific for breast cancer nodal metastases. We hypothesize that false-negative result predicts minimal axillary disease (<=2 +nodes). METHODS: A retrospective review of breast cancer patients receiving AUS identified T1/T2 tumors and positive sentinel node with axillary dissection. Chi square analysis was performed using Fisher's exact test. RESULTS: Of 903 AUS cases, 384 had T1/T2 tumors. False-negative rate of AUS +/- FNA was 48% and 45%, respectively. Of 384 cases, 73 were sentinel node positive and had axillary dissection; 55 (75.3%) were invasive ductal carcinoma (IDC). Negative predictive value for greater than or equal to 2 nodes was 71% in IDC versus 44% for in non IDC patients. Sixteen (29.0%) IDC patients had greater than or equal to 3 positive nodes versus 10 (55.5%) non-IDC (P = .05) patients. CONCLUSION: The high negative predictive value for AUS with FNA for IDC suggests that the AUS plus FNA interpretation may be better limited to the ipsilateral nodes of IDC. PMID- 25118160 TI - Geographic variation in radiologist capacity and widespread implementation of lung cancer CT screening. AB - BACKGROUND: Newly released United States Preventive Services Task Force (USPSTF) recommendations for lung cancer screening are expected to increase demand for low dose computed tomography scanning, but health system capacity constraints might threaten the scale-up of screening. OBJECTIVES: To estimate the prevalence of capacity constraints in the radiologist workforce and resulting potential disparities in access to lung cancer screening. METHODS: We combined information from health interview surveys to estimate the numbers of smokers who meet the USPSTF eligibility criteria, and information from administrative datasets to estimate the numbers of radiologists and the numbers of scans they currently interpret in Health Service Areas (HSAs) nationwide. We estimated and mapped the prevalence of capacity constrained HSAs - those having a greater than 5% or greater than 25% projected increase in scans over current levels from scaling up screening - and used descriptive statistics and logistic regressions to identify HSA characteristics associated with capacity constraints. RESULTS: Scaling up lung cancer screening would increase imaging procedures by an average of 4% across HSAs. Of the 9.6 million eligible smokers, 1,023,943 lived in HSAs with increases of at least 5%. HSAs that were rural, with many eligible smokers, and disproportionately Hispanic or low-income smokers had significantly higher odds of facing capacity constraints. CONCLUSIONS: Disparities in access to lung cancer screening appear likely unless policy makers target HSAs with few radiologists for additional resources. Radiologists should be able to absorb the workload imposed by lung cancer screening in most areas of the country. PMID- 25118163 TI - Repair of recurrent hernia after biologic mesh failure in abdominal wall reconstruction. AB - BACKGROUND: Biologic mesh is commonly used in abdominal wall reconstruction but may result in increased hernia recurrence. There are minimal data on repair of these recurrent hernias. METHODS: We conducted a retrospective chart review of 24 patients presenting to a single surgeon with recurrent ventral hernia, previously repaired with biologic mesh. RESULTS: Seventeen of 24 study patients underwent open repair, including 5 revisions of incomplete external oblique release. Mesh was polypropylene in 11 patients and fenestrated condensed polytetrafluoroethylene in 3 patients. In 1 patient, no mesh was used. In 2 patients, bridged biologic mesh was used because of risk of exposure. All biologic repairs have since recurred. Complications occurred in 3 of 15 prosthetic mesh patients and in all biologic mesh patients. CONCLUSIONS: Prior components release can be repeated if computed tomography scan reveals incomplete release. Recurrence is common after bridged biologic mesh repair. Conventional mesh can be used safely in many recurrent abdominal hernias after biologic mesh failure. PMID- 25118165 TI - A small intestinal organoid model of non-invasive enteric pathogen-epithelial cell interactions. AB - Organoids mirror in vivo tissue organization and are powerful tools to investigate the development and cell biology of the small intestine. However, their application for the study of host-pathogen interactions has been largely unexplored. We have established a model using microinjection of organoids to mimic enteric infection, allowing for direct examination of pathogen interactions with primary epithelial cells in the absence of confounding variables introduced by immune cells or the commensal microbiota. We investigated the impact of Paneth cell alpha-defensin antimicrobial peptides on bacterial growth. We demonstrate that organoids form a sealed lumen, which contains concentrations of alpha defensins capable of restricting growth of multiple strains of Salmonella enterica serovar Typhimurium for at least 20 h postinfection. Transgenic expression of human defensin 5 in mouse organoids lacking functional murine alpha defensins partially restored bacterial killing. We also found that organoids from NOD2(-/-) mice were not impaired in alpha-defensin expression or antibacterial activity. This model is optimized for the study of non-invasive bacteria but can be extended to other enteric pathogens and is amenable to further genetic manipulation of both the host and microbe to dissect this critical interface of host defense. PMID- 25118164 TI - A meta-analysis of complications following deceased donor liver transplant. AB - BACKGROUND: Liver transplantation is a complex surgery associated with high rates of postoperative complications. While national outcomes data are available, national rates of most complications are unknown. DATA SOURCES: A systematic review of the literature reporting rates of postoperative complications between 2002 and 2012 was performed. A cohort of 29,227 deceased donor liver transplant recipients from 74 studies was used to calculate pooled incidences for 17 major postoperative complications. CONCLUSIONS: This is the first comprehensive review of postoperative complications after liver transplantation and can serve as a guide for transplant and nontransplant clinicians. Efforts to collect national data on complications, such as through the National Surgical Quality Improvement Program, would improve the ability to provide patients with informed consent, serve as a tool for individual center performance monitoring, and provide a central source against which to measure interventions aimed at improving patient care. PMID- 25118166 TI - Type II cytokines impair host defense against an intracellular fungal pathogen by amplifying macrophage generation of IL-33. AB - Interleukin (IL)-4 subverts protective immunity to multiple intracellular pathogens, including the fungus Histoplasma capsulatum. Previously, we reported that H. capsulatum-challenged CCR2(-/-) mice manifest elevated pulmonary fungal burden owing to exaggerated IL-4. Paradoxical to our anticipation in IL-33 driving IL-4, we discovered that the latter prompted IL-33 in mutant mice. In infected CCR2(-/-) animals, amplified IL-33 succeeded the heightened IL-4 response and inhibition of IL-4 signaling decreased IL-33. Moreover, macrophages, but not epithelial cells or dendritic cells, from these mice expressed higher IL 33 in comparison with controls. Dissection of mechanisms that promulgated IL-33 revealed type-II cytokines and H. capsulatum synergistically elicited an IL-33 response in macrophages via signal transducer and activator of transcription factor 6/interferon-regulatory factor-4 and Dectin-1 pathways, respectively. Neutralizing IL-33 in CCR2(-/-) animals, but not controls, enhanced their resistance to histoplasmosis. Thus we describe a previously unrecognized role for IL-4 in instigating IL-33 in macrophages. Furthermore, in the presence of intracellular fungal pathogens, the type-II cytokine-driven IL-33 response impairs immunity. PMID- 25118167 TI - In vivo attenuation and genetic evolution of a ST247-SCCmecI MRSA clone after 13 years of pathogenic bronchopulmonary colonization in a patient with cystic fibrosis: implications of the innate immune response. AB - Methicillin-resistant Staphylococcus aureus (MRSA) causes chronic pulmonary infections in patients with cystic fibrosis (CF). This study tracks the 13-year evolution (1996-2009) of a single MRSA clone in a male patient with CF, evaluating both the host immunogenic response and the microbial variations. Whole genome sequencing was performed for the initial (CF-96) and evolved (CF-09) isolates. The immunogenicity of CF-96 and CF-09 was evaluated by incubation with innate immune cells from healthy volunteers. We also studied the patient's innate immune response profile, cytokine production, expression of triggering receptor expressed on myeloid cells-1 (TREM-1), and phagocytosis. A total of 30 MRSA ST247 SCCmecI-pvl(-) isolates were collected, which evidenced a genome size reduction from the CF-96 ancestor to the evolved CF-09 strain. Up to six changes in the spa type were observed over the course of the 13-year evolution. Cytokine production, TREM-1 expression, and phagocytosis were significantly lower for the healthy volunteer monocytes exposed to CF-09, compared with those exposed to CF-96. Patient monocytes exhibited a reduced inflammatory response when challenged with CF-09. Genetic changes in MRSA, leading to reduced immunogenicity and entry into the refractory state, may contribute to the attenuation of virulence and efficient persistence of the bacteria in the CF lung. PMID- 25118168 TI - Time to onset of pain: effects of magnitude and location for static pressures applied to the plantar foot. AB - Mechanisms that cause foot discomfort during prolonged standing are poorly understood. There is currently no method for evaluating discomfort associated with low levels of static pressure that are typical during standing. Pain thresholds were measured for 20 healthy participants by applying five levels of static pressure at different plantar foot locations. A survival analysis was performed to determine the effects of pressure magnitude and foot location on the time until pain onset. Time to pain onset was significantly affected by pressure magnitude (P < 0.001); time decreased as pressure increased. Foot location was also significant (P < 0.001); greatest times to pain onset (least sensitive) were observed under the heel and fifth metatarsal head, shortest times (most sensitive) were found under the midfoot. This research presents a novel methodology for evaluating static pressure that may be applicable to product design. PMID- 25118170 TI - A cancer cell-activatable aptamer-reporter system for one-step assay of circulating tumor cells. AB - The current antibody-mediated numeration assays of circulating tumor cells (CTCs) require multiple steps and are time-consuming. To overcome these technical limitations, a cancer cell-activatable aptamer-reporter was formulated by conjugating a biomarker-specific aptamer sequence with paired fluorochrome quencher molecules. In contrast to the antibody probes, the intact aptamer reporter was optically silent in the absence of cells of interest. However, when used in an assay, the aptamer selectively targeted cancer cells through interaction with a specific surface biomarker, which triggered internalization of the aptamer-reporter and, subsequently, into cell lysosomes. Rapid lysosomal degradation of the aptamer-reporter resulted in separation of the paired fluorochrome-quencher molecules. The released fluorochrome emitted bright fluorescent signals exclusively within the targeted cancer cells, with no background noise in the assay. Thus, the assays could be completed in a single step within minutes. By using this one-step assay, CTCs in whole blood and marrow aspirate samples of patients with lymphoma tumors were selectively highlighted and rapidly detected with no off-target signals from background blood cells. The development of the cancer cell-activatable aptamer-reporter system allows for the possibility of a simple and robust point-of-care test for CTC detection, which is currently unavailable. PMID- 25118171 TI - Hybrid Nanomaterial Complexes for Advanced Phage-guided Gene Delivery. AB - Developing nanomaterials that are effective, safe, and selective for gene transfer applications is challenging. Bacteriophages (phage), viruses that infect bacteria only, have shown promise for targeted gene transfer applications. Unfortunately, limited progress has been achieved in improving their potential to overcome mammalian cellular barriers. We hypothesized that chemical modification of the bacteriophage capsid could be applied to improve targeted gene delivery by phage vectors into mammalian cells. Here, we introduce a novel hybrid system consisting of two classes of nanomaterial systems, cationic polymers and M13 bacteriophage virus particles genetically engineered to display a tumor-targeting ligand and carry a transgene cassette. We demonstrate that the phage complex with cationic polymers generates positively charged phage and large aggregates that show enhanced cell surface attachment, buffering capacity, and improved transgene expression while retaining cell type specificity. Moreover, phage/polymer complexes carrying a therapeutic gene achieve greater cancer cell killing than phage alone. This new class of hybrid nanomaterial platform can advance targeted gene delivery applications by bacteriophage. PMID- 25118169 TI - Reduced apolipoprotein glycosylation in patients with the metabolic syndrome. AB - OBJECTIVE: The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls. METHODS: Very low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D) gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays. RESULTS: Metabolic syndrome patients differed from healthy controls in the following ways: (1) total plasma--apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL--apoB, apoC3, and apoE were increased; (3) LDL--apoC3 was increased, (4) HDL--associated constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for all). In patients with metabolic syndrome, the most extensively glycosylated (di sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001). CONCLUSIONS: Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined. PMID- 25118176 TI - Microbial contamination of enteral feeding products in thermoneutral and hyperthermal ICU environments. AB - BACKGROUND: Temperature is known to affect bacterial growth, but current safety recommendations for enteral formula are based on studies conducted in thermoneutral environments, which are not representative of select burn intensive care units (ICUs) that are kept therapeutically hyperthermal. This project evaluated microbial growth in 3 enteral feeding systems: closed, open, and open with modular additives (modular tube feeding [MTF]) exposed to 2 different environments. PROCEDURES: Product for each of the 3 systems was prepared and hung in both a thermoneutral (23.3 degrees C) and a hyperthermal (32.5 degrees C) ICU room. At baseline, 4 hours, and 8 hours, samples were plated and incubated overnight and the number of colony-forming units (CFUs) counted. FINDINGS: In the thermoneutral and hyperthermal environments, there was no evidence of microbial growth in the open or closed feeding systems at any time point. The MTF exhibited baseline contamination with a median of 10 CFUs (95% CI, 8-16) and significant growth over time to 54 CFUs (95% CI, 20-230) by 8 hours in the thermoneutral setting. In the hyperthermal environment, the MTF showed baseline contamination of 390 CFUs (95% CI, 40-1600) and significant growth over time, with 30% of samples exhibiting contamination levels exceeding Food and Drug Administration standards by 4 hours and CFUs being too numerous to count by 8 hours. CONCLUSION: CFUs in enteral formula did not differ between open and closed feeding systems in either environment for up to 8 hours; however, the addition of modulars to open systems may result in an unacceptable risk of contamination in hyperthermal environments. PMID- 25118177 TI - Efficacy and safety of using L-cysteine as a catheter-clearing agent for nonthrombotic occlusions of central venous catheters in children. AB - Critically ill pediatric patients, especially in the intensive care unit, receive multiple medications and have a higher risk of central venous catheter (CVC) occlusion. If an occlusion occurs immediately after the administration of multiple medications or incompatible medications, either an acidic solution such as 0.1 N hydrochloric acid (HCl) or a basic solution of 1 mEq/mL sodium bicarbonate or 0.1 N sodium hydroxide can be used. However, compounding and storing of 0.1 N HCl has become more complex due to USP <797> guidelines for sterile compounding, and an alternative is needed. We report a series of cases in which L-cysteine was used instead of HCl to clear CVCs occluded due to administration of multiple medications. L-cysteine is a commercially available, sterile solution with a pH of 1-2.5. CVC occlusion was resolved in 10 of the 16 episodes in 13 patients. Two of the 16 occlusions were phenytoin related and would not have responded. An L-cysteine dose of 50 mg was used during 10 of the 16 episodes, 100 mg during 5 episodes, and 25 mg during 1 episode. A correlation between catheter clearance and dose was not observed. Occlusion resolution due to L-cysteine was not correlated to the prior use of tissue plasminogen activator. Metabolic acidosis, adverse effects, or damage to the catheters due to L-cysteine were not observed. On the basis of this limited experience, we propose L-cysteine as an effective alternative to 0.1 N HCl for clearing CVC occlusions caused by drugs with an acidic pKa. PMID- 25118175 TI - Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli. AB - Clustered regularly interspaced short palindromic repeats (CRISPR) together with CRISPR-associated (Cas) proteins form the CRISPR/Cas system to defend against foreign nucleic acids of bacterial and archaeal origin. In the I-E subtype CRISPR/Cas system, eleven subunits from five Cas proteins (CasA1B2C6D1E1) assemble along a CRISPR RNA (crRNA) to form the Cascade complex. Here we report on the 3.05 A crystal structure of the 405-kilodalton Escherichia coli Cascade complex that provides molecular details beyond those available from earlier lower resolution cryo-electron microscopy structures. The bound 61-nucleotide crRNA spans the entire 11-protein subunit-containing complex, where it interacts with all six CasC subunits (named CasC1-6), with its 5' and 3' terminal repeats anchored by CasD and CasE, respectively. The crRNA spacer region is positioned along a continuous groove on the concave surface generated by the aligned CasC1-6 subunits. The five long beta-hairpins that project from individual CasC2-6 subunits extend across the crRNA, with each beta-hairpin inserting into the gap between the last stacked base and its adjacent splayed counterpart, and positioned within the groove of the preceding CasC subunit. Therefore, instead of continuously stacking, the crRNA spacer region is divided into five equal fragments, with each fragment containing five stacked bases flanked by one flipped-out base. Each of those crRNA spacer fragments interacts with CasC in a similar fashion. Furthermore, our structure explains why the seed sequence, with its outward-directed bases, has a critical role in target DNA recognition. In conclusion, our structure of the Cascade complex provides novel molecular details of protein-protein and protein-RNA alignments and interactions required for generation of a complex mediating RNA-guided immune surveillance. PMID- 25118178 TI - Cholesterol metabolism is altered in Rett syndrome: a study on plasma and primary cultured fibroblasts derived from patients. AB - Rett (RTT) syndrome is a severe neurological disorder that affects almost exclusively females. Several detectable mutations in the X-linked methyl-CpG binding protein 2 gene (MECP2) are responsible for the onset of the disease. MeCP2 is a key transcription regulator involved in gene silencing via methylation dependent remodeling of chromatin. Recent data highlight that lipid metabolism is perturbed in brains and livers of MECP2-null male mice. In addition, altered plasma lipid profile in RTT patients has been observed. Thus, the aim of the work is to investigate the protein network involved in cholesterol homeostasis maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A reductase (HMGR), sterol regulatory element binding proteins (SREBPs), low density lipoprotein receptor (LDLr) and scavenger receptor B-1 (SRB-1) was assessed in cultured skin fibroblasts from unaffected individuals and RTT patients. In addition, lipid profile and the abundance of proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed on plasma samples. The obtained results demonstrate that the main proteins belonging to cholesterol regulatory network are altered in RTT female patients, providing the proof of principle that cholesterol metabolism may be taken into account as a new target for the treatment of specific features of RTT pathology. PMID- 25118179 TI - Assessment of the neutrophilic antibody-dependent respiratory burst (ADRB) response to Plasmodium falciparum. AB - Semi-immunity against Pf malaria is based on a combination of cellular and humoral immune responses. PMNs and IgGs are considered important components of this process, but the underlying mechanisms are unclear. We investigated the neutrophilic ADRB by analyzing the production of ROS in response to Pf antigen specific IgGs bound to solid-phase immobilized antigens (sADRB) or whole merozoites (mADRB). We found that the PMN stimulations in each assay were based on different underlying mechanisms, demonstrating the importance of the assay set up for the evaluation of antibody-triggered PMN responses. In the sADRB assay, ROS were produced externally, and by specific blocking of CD32(a)/FcgammaRII(a), the immediate neutrophilic response was abolished, whereas the removal of CD16(b)/FcgammaRIII(b) had no substantial effect. The key role of CD32(a) was confirmed using CD16(b)-deficient PMNs, in which similar changes of neutrophilic ADRB profiles were recorded after treatment. In the mADRB assay, ROS were produced almost exclusively within the cell, suggesting that the underlying mechanism was phagocytosis. This was confirmed using an additional phagocytosis assay, in which PMNs specifically ingested merozoites opsonized with Ghanaian plasma IgGs, seven times more often than merozoites opsonized with European plasma IgGs (P<0.001). Our data show that assay set-ups used to evaluate the responses of PMNs and perhaps other effector cells must be chosen carefully to evaluate the appropriate cellular responses. Our robust, stable, and well characterized methods could therefore be useful in malaria vaccine studies to analyze the antimalarial effector function of antibodies. PMID- 25118181 TI - Rheinheimera arenilitoris sp. nov., isolated from seashore sand. AB - A Gram-stain-negative, non-flagellated, aerobic and ovoid or rod-shaped bacterium, designated J-MS1(T), was isolated from seashore sand in the South Sea, South Korea, and subjected to a polyphasic taxonomic study. Strain J-MS1(T) was found to grow optimally at 30 degrees C and pH 7.0-8.0. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain J-MS1(T) belonged to the genus Rheinheimera, clustering coherently with the type strain of Rheinheimera chironomi and sharing 98.34% sequence similarity. Strain J-MS1(T) exhibited 16S rRNA gene sequence similarity of 94.26-96.98% to the type strains of the other species of the genus Rheinheimera. In the phylogenetic trees based on gyrB sequences, strain J-MS1(T) clustered with the type strain of R. chironomi, with which it shared the highest sequence similarity (86.97%). Strain J-MS1(T) contained Q-8 as the predominant ubiquinone and summed feature 3 (C(16:1)omega7c and/or C(16:1)omega6c), C(16:0) and C(18:1)omega7c as the major fatty acids. The major polar lipids detected in strain J-MS1(T) and in the type strain of R. chironomi were phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content of strain J-MS1(T) was 49.8 mol% and its mean DNA-DNA relatedness value with R. chironomi LMG 23818(T) was 12%. Differential phenotypic properties, together with its phylogenetic and genetic distinctiveness, revealed that strain J-MS1(T) is separated from recognized species of the genus Rheinheimera. On the basis of the data presented, strain J-MS1(T) is considered to represent a novel species of the genus Rheinheimera, for which the name Rheinheimera arenilitoris sp. nov. is proposed. The type strain is J-MS1(T) ( =KCTC 42112(T) =CECT 8623(T)). PMID- 25118180 TI - Compact genome of the Antarctic midge is likely an adaptation to an extreme environment. AB - The midge, Belgica antarctica, is the only insect endemic to Antarctica, and thus it offers a powerful model for probing responses to extreme temperatures, freeze tolerance, dehydration, osmotic stress, ultraviolet radiation and other forms of environmental stress. Here we present the first genome assembly of an extremophile, the first dipteran in the family Chironomidae, and the first Antarctic eukaryote to be sequenced. At 99 megabases, B. antarctica has the smallest insect genome sequenced thus far. Although it has a similar number of genes as other Diptera, the midge genome has very low repeat density and a reduction in intron length. Environmental extremes appear to constrain genome architecture, not gene content. The few transposable elements present are mainly ancient, inactive retroelements. An abundance of genes associated with development, regulation of metabolism and responses to external stimuli may reflect adaptations for surviving in this harsh environment. PMID- 25118182 TI - Role of editorial and peer review processes in publication bias: analysis of drug trials submitted to eight medical journals. AB - BACKGROUND: Publication bias is generally ascribed to authors and sponsors failing to submit studies with negative results, but may also occur after submission. We evaluated whether submitted manuscripts on randomized controlled trials (RCTs) with drugs are more likely to be accepted if they report positive results. METHODS: Manuscripts submitted from January 2010 through April 2012 to one general medical journal (BMJ) and seven specialty journals (Annals of the Rheumatic Diseases, British Journal of Ophthalmology, Gut, Heart, Thorax, Diabetologia, and Journal of Hepatology) were included, if at least one study arm assessed the efficacy or safety of a drug and a statistical test was used to evaluate treatment effects. Publication status was retrospectively retrieved from submission systems or provided by journals. Sponsorship and trial results were extracted from manuscripts and classified according to predefined criteria. Main outcome measure was acceptance for publication. RESULTS: Of 15,972 manuscripts submitted, 472 (3.0%) were drug RCTs, of which 98 (20.8%) were published. Among submitted drug RCTs, 287 (60.8%) had positive and 185 (39.2%) negative results. Of these, 60 (20.9%) and 38 (20.5%), respectively, were published. Manuscripts on non-industry trials (n = 213) reported positive results in 138 (64.8%) manuscripts, compared to 71 (47.7%) on industry-supported trials (n = 149), and 78 (70.9%) on industry-sponsored trials (n = 110). Twenty-seven (12.7%) non industry trials were published, compared to 27 (18.1%) industry-supported and 44 (40.0%) industry-sponsored trials. After adjustment for other trial characteristics, manuscripts reporting positive results were not more likely to be published (OR, 1.00; 95% CI, 0.61 to 1.66). Submission to specialty journals, sample size, multicentre status, journal impact factor, and corresponding authors from Europe or US were significantly associated with publication. CONCLUSIONS: For the selected journals, there was no tendency to preferably publish manuscripts on drug RCTs that reported positive results, suggesting that publication bias may occur mainly prior to submission. PMID- 25118183 TI - Telomerase stimulates ribosomal DNA transcription under hyperproliferative conditions. AB - In addition to performing its canonical function, Telomerase Reverse Transcriptase (TERT) has been shown to participate in cellular processes independent of telomerase activity. Furthermore, although TERT mainly localizes to Cajal bodies, it is also present within the nucleolus. Because the nucleolus is the site of rDNA transcription, we investigated the possible role of telomerase in regulating RNA polymerase I (Pol I). Here we show that TERT binds to rDNA and stimulates transcription by Pol I during liver regeneration and Ras induced hyperproliferation. Moreover, the inhibition of telomerase activity by TERT- or TERC-specific RNA interference, the overexpression of dominant-negative TERT, and the application of the telomerase inhibitor imetelstat reduce Pol I transcription and the growth of tumour cells. In vitro, telomerase can stimulate the formation of the transcription initiation complex. Our results demonstrate how non-canonical features of telomerase may direct Pol I transcription in oncogenic and regenerative hyperproliferation. PMID- 25118184 TI - Relationship between visuospatial neglect and kinesthetic deficits after stroke. AB - BACKGROUND: After stroke, visuospatial and kinesthetic (sense of limb motion) deficits are common, occurring in approximately 30% and 60% of individuals, respectively. Although both types of deficits affect aspects of spatial processing necessary for daily function, few studies have investigated the relationship between these 2 deficits after stroke. OBJECTIVE: We aimed to characterize the relationship between visuospatial and kinesthetic deficits after stroke using the Behavioral Inattention Test (BIT) and a robotic measure of kinesthetic function. METHODS: Visuospatial attention (using the BIT) and kinesthesia (using robotics) were measured in 158 individuals an average of 18 days after stroke. In the kinesthetic matching task, the robot moved the participant's stroke-affected arm at a preset direction, speed, and magnitude. Participants mirror-matched the robotic movement with the less/unaffected arm as soon as they felt movement in their stroke affected arm. RESULTS: We found that participants with visuospatial inattention (neglect) had impaired kinesthesia 100% of the time, whereas only 59% of participants without neglect were impaired. For those without neglect, we observed that a higher percentage of participants with lower but passing BIT scores displayed impaired kinesthetic behavior (78%) compared with those participants who scored perfect or nearly perfect on the BIT (49%). CONCLUSIONS: The presence of visuospatial neglect after stroke is highly predictive of the presence of kinesthetic deficits. However, the presence of kinesthetic deficits does not necessarily always indicate the presence of visuospatial neglect. Our findings highlight the importance of assessment and treatment of kinesthetic deficits after stroke, especially in patients with visuospatial neglect. PMID- 25118185 TI - Recent research on the growth plate: Regulation, bone growth defects, and potential treatments. PMID- 25118188 TI - Oculo-auriculo-vertebral spectrum: a review of the literature and genetic update. AB - Oculo-auriculo-vertebral spectrum (OAVS, OMIM 164 210) is a developmental disorder primarily involving structures derived from the first and second pharyngeal arches during embryogenesis. The phenotype is clinically heterogeneous and is typically characterised by abnormal development of the ear, mandible anomalies and defects of the vertebral column. OAVS may occur as a multiple congenital abnormality, and associated findings include anomalies of the eye, brain, heart, kidneys and other organs and systems. Both genetic and environmental factors are thought to contribute to this craniofacial condition, however, the mechanisms are still poorly understood. Here, we present a review of the literature on OAVS, discussing what is known about the aetiology, candidate loci, possible mechanisms and the range of clinical features that characterise this condition. We also comment on some important aspects of recurrence risk counselling to aid clinical management. PMID- 25118186 TI - Bright and fast multicoloured voltage reporters via electrochromic FRET. AB - Genetically encoded fluorescent reporters of membrane potential promise to reveal aspects of neural function not detectable by other means. We present a palette of multicoloured brightly fluorescent genetically encoded voltage indicators with sensitivities from 8-13% DeltaF/F per 100 mV, and half-maximal response times from 4-7 ms. A fluorescent protein is fused to an archaerhodopsin-derived voltage sensor. Voltage-induced shifts in the absorption spectrum of the rhodopsin lead to voltage-dependent nonradiative quenching of the appended fluorescent protein. Through a library screen, we identify linkers and fluorescent protein combinations that report neuronal action potentials in cultured rat hippocampal neurons with a single-trial signal-to-noise ratio from 7 to 9 in a 1 kHz imaging bandwidth at modest illumination intensity. The freedom to choose a voltage indicator from an array of colours facilitates multicolour voltage imaging, as well as combination with other optical reporters and optogenetic actuators. PMID- 25118187 TI - The association between race and Crohn's disease phenotype in the Western Cape population of South Africa, defined by the Montreal Classification System. AB - BACKGROUND: Inter-racial differences in disease characteristics and in the management of Crohn's disease (CD) have been described in African American and Asian subjects, however for the racial groups in South Africa, no such recent literature exists. METHODS: A cross sectional study of all consecutive CD patients seen at 2 large inflammatory bowel disease (IBD) referral centers in the Western Cape, South Africa between September 2011 and January 2013 was performed. Numerous demographic and clinical variables at diagnosis and date of study enrolment were identified using an investigator administered questionnaire as well as clinical examination and patient case notes. Using predefined definitions, disease behavior was stratified as 'complicated' or 'uncomplicated'. RESULTS: One hundred and ninety four CD subjects were identified; 35 (18%) were white, 152 (78%) were Cape Coloured and 7(4%) were black. On multiple logistic regression analysis Cape Coloureds were significantly more likely to develop 'complicated' CD (60% vs. 9%, p = 0.023) during the disease course when compared to white subjects. In addition, significantly more white subjects had successfully discontinued cigarette smoking at study enrolment (31% vs. 7% reduction, p = 0.02). No additional inter-racial differences were found. A low proportion of IBD family history was observed among the non-white subjects. CONCLUSIONS: Cape Coloured patients were significantly more likely to develop 'complicated' CD over time when compared to whites. PMID- 25118189 TI - Does marriage really matter to health? Intra- and inter-country evidence from China, Japan, Taiwan, and the Republic of Korea. AB - BACKGROUND: The health benefits of marriage have been demonstrated mainly by studies on Western populations. This study aims to test whether the benefits are also valid in East Asian populations. METHODOLOGY/PRINCIPAL FINDINGS: Individuals (n = 8,538) from China, Japan, Taiwan, and the Republic of Korea were sampled from the 2006 East Asian Social Survey. The association between self-rated health status and two marriage-related independent variables was analyzed using multivariate logistic regression models. In a two-level analysis for individuals from all countries, married individuals were more likely to report very good or good health compared to their never-married counterparts [odds ratio (OR) 1.56; 95% confidence interval (95% CI) 1.16-2.10]. However, the addition of marital satisfaction disintegrated the significant association of marriage with self rated health. Married individuals in satisfying marriages were more likely to report very good or good health compared with never-married individuals (OR 1.85; 95% CI 1.37-2.50). In contrast, married individuals in dissatisfying marriages were as likely to report very good or good health as never-married individuals (OR 0.78; 95% CI 0.50-1.24). In a one-level analysis for each country, the importance of marital satisfaction varied greatly across countries. Unlike in other countries, in Japan, married individuals in dissatisfying marriages were about half as likely to report very good or good health as never-married individuals (OR 0.51, 95% CI 0.31-0.83), thereby showing no significant benefits from marriage with regard to self-rated health. CONCLUSION/SIGNIFICANCE: The present study of East Asian countries suggests that marital satisfaction is of greater importance in determining self-rated health than marriage itself, and that the importance of marital satisfaction varies across countries. Further research is required to better understand the relationship between marital satisfaction and self-rated health in different socio-cultural settings, and to establish effective social policies aiming at improving public health. PMID- 25118190 TI - Secretory Leukocyte Protease Inhibitor (SLPI): Emerging Roles in CNS Trauma and Repair. AB - At first glance, secretory leukocyte protease inhibitor (SLPI) would appear to have little relevance to the central nervous system (CNS). This serine protease inhibitor is most commonly found in mucosal fluids such as saliva and is best known for its anti-inflammatory and antimicrobial properties. It has been shown to promote wound healing by reducing expression of pro-inflammatory cytokines, and it can also inhibit bacterial growth and block HIV infection of macrophages. In the past 10 years, however, several studies have reported that SLPI is strongly up-regulated in response to CNS injury and that exogenous administration of SLPI is neuroprotective. It has also been shown that SLPI can overcome inhibition by CNS myelin and promote axonal regeneration. In this review, we will discuss these studies, examine the molecular mechanisms underlying SLPI's effects, and consider SLPI's potential for therapeutic use in cerebral ischemia, spinal cord injury, and multiple sclerosis. PMID- 25118191 TI - Endovascular treatment in patients with acute ischemic stroke and apparent occlusion of the extracranial internal carotid artery on CTA. AB - BACKGROUND: Intra-arterial treatment is gaining importance in acute ischemic stroke, but its role in patients with apparent occlusion of the extracranial internal carotid artery (ICA) on computed tomographic angiography (CTA) is inconclusive. OBJECTIVE: To review retrospectively the results of intra-arterial treatment in patients with stroke and apparent extracranial ICA occlusion. METHODS: In more than 3000 patients with stroke admitted to our institution during 2008-2013, and the subgroup with suboptimal results after intravenous thrombolysis (IVT), CTA showed the absence of contrast in the extracranial ICA in 16 patients. Angiography showed true occlusion of the extracranial ICA in 10 and pseudo-occlusion in 6 patients. Treatment was considered technically successful when Thrombolysis in Cerebral Infarction scale (TICI) scores improved to 2 or 3 and clinically successful when the National Institutes of Health Stroke Scale (NIHSS) improved by at least 10 points or a NIHSS score of 0 or 1 was found at discharge. RESULTS: Recanalization was achieved in 5 of 6 patients with pseudo occlusions and in 6 of 10 patients with true occlusion of the extracranial ICA. Favorable clinical outcomes were seen in 3 of 6 patients with pseudo-occlusions and in 4 of 10 patients with true occlusions. Four patients died, and in these patients infarction of >15% of the affected hemisphere had been seen on admission CT. CONCLUSIONS: In cases of acute stroke and apparent occlusion of the extracranial ICA, intra-arterial treatment should be considered, especially when IVT fails and <15% of the hemisphere is infarcted on CT. Endovascular treatment may be beneficial especially in pseudo-occlusions but also in true occlusions of the extracranial ICA. PMID- 25118192 TI - Angiographic factors influencing the success of endovascular treatment of arteriovenous malformations involving the corpus callosum. AB - OBJECTIVE: Arteriovenous malformations (AVMs) of the corpus callosum are rare lesions, accounting for 9-11% of brain AVMs. Microsurgical resection of such lesions is difficult because of their deep location, and also because of possible neuropsychological disasters resulting from extended callosal resection. The introduction of endovascular and radiation therapies has fundamentally changed the outcome of these lesions. METHODS: We prospectively collected clinical and angiographic data on cerebral AVMs from 1995. We reviewed data from patients treated for an AVM of the corpus callosum and identified the factors influencing the endovascular approach of such lesions. RESULTS: 38 patients (mean age 31 years) were consecutively treated by endovascular techniques. 78.9% (30 cases) of patients presented with intracranial hemorrhage. 15 AVMs (39.5%) were anterior, 18 (47.4%) were posterior, and five (13.1%) were holocallosal. The Spetzler Martin grade was I in two cases (5.2%), II in 20 cases (52.6%), III in nine cases (23.7%), IV in six cases (15.8%), and V in one case (2.6%). The nidus was compact in 19 cases (50%), diffuse in 13 (34.2%), and multifocal in six (15.8%). Both anterior and posterior circulation branches fed 14 nidi (36.8%). Venous drainage was superficial in three cases (7.9%), deep in 28 (73.7%), and both in seven cases (18.4%). 104 sessions were performed, with a procedural complication rate of 6.7%. Mean follow-up was 43.6 months, with the last modified Rankin Scale score <3 in 33 cases (86.8%). 22 patients (57.9%) were totally cured. Univariate analysis of factors influencing the success of endovascular treatment showed that Spetzler-Martin grade >=3 (p=0.046), nidus >30 mm (p=0.02), extension in an eloquent area (p=0.03), and holocallosal type (p0.005) significantly diminished the chances of cure of the AVM. CONCLUSIONS: AVMs of the corpus callosum seems to be difficult to treat with endovascular therapy alone. The goal of embolization should be prevention of (re) bleeding and a decrease in nidus size. Our experience regarding this sub-pathology suggests that a combination of endovascular therapy and radiotherapy may be the best option. PMID- 25118193 TI - Balloon-augmented Onyx embolization of cerebral arteriovenous malformations using a dual-lumen balloon: a multicenter experience. AB - INTRODUCTION: Conventional Onyx embolization of cerebral arteriovenous malformations (AVMs) requires lengthy procedure and fluoroscopy times to form an adequate 'proximal plug' which allows forward nidal penetration while preventing reflux and non-targeted embolization. We review our experience with balloon augmented Onyx embolization of cerebral AVMs using a dual-lumen balloon catheter technique designed to minimize these challenges. METHODS: Retrospectively acquired data for all balloon-augmented cerebral AVM embolizations performed between 2011 and 2014 were obtained from four tertiary care centers. For each procedure, at least one Scepter C balloon catheter was advanced into the AVM arterial pedicle of interest and Onyx embolization was performed through the inner lumen after balloon inflation via the outer lumen. RESULTS: Twenty patients underwent embolization with the balloon-augmented technique over 24 discreet treatment episodes. There were 37 total arterial pedicles embolized with the balloon-augmented technique, a mean of 1.9 per patient (range 1-5). The treated AVMs were heterogeneous in their location and size (mean 3.3+/-1.6 cm). Mean fluoroscopy time for each procedure was 48+/-26 min (28 min per embolized pedicle). Two Scepter C balloon catheter-related complications (8.3% of embolization sessions, 5.4% of pedicles embolized) were observed: an intraprocedural rupture of a feeding pedicle and fracture and retention of a catheter fragment. CONCLUSIONS: This multicenter experience represents the largest reported series of balloon-augmented Onyx embolization of cerebral AVMs. The technique appears safe and effective in the treatment of AVMs, allowing more efficient and controlled injection of Onyx with a decreased risk of reflux and decreased fluoroscopy times. PMID- 25118194 TI - A high-density genetic map for soybean based on specific length amplified fragment sequencing. AB - Soybean is an important oil seed crop, but very few high-density genetic maps have been published for this species. Specific length amplified fragment sequencing (SLAF-seq) is a recently developed high-resolution strategy for large scale de novo discovery and genotyping of single nucleotide polymorphisms. SLAF seq was employed in this study to obtain sufficient markers to construct a high density genetic map for soybean. In total, 33.10 Gb of data containing 171,001,333 paired-end reads were obtained after preprocessing. The average sequencing depth was 42.29 in the Dongnong594, 56.63 in the Charleston, and 3.92 in each progeny. In total, 164,197 high-quality SLAFs were detected, of which 12,577 SLAFs were polymorphic, and 5,308 of the polymorphic markers met the requirements for use in constructing a genetic map. The final map included 5,308 markers on 20 linkage groups and was 2,655.68 cM in length, with an average distance of 0.5 cM between adjacent markers. To our knowledge, this map has the shortest average distance of adjacent markers for soybean. We report here a high density genetic map for soybean. The map was constructed using a recombinant inbred line population and the SLAF-seq approach, which allowed the efficient development of a large number of polymorphic markers in a short time. Results of this study will not only provide a platform for gene/quantitative trait loci fine mapping, but will also serve as a reference for molecular breeding of soybean. PMID- 25118195 TI - Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated respiratory disease. AB - OBJECTIVE: This study aimed to assess sinonasal outcomes in patients with aspirin exacerbated respiratory disease (AERD) undergoing aspirin desensitization following endoscopic sinus surgery (ESS). STUDY DESIGN: Case series with chart review. SETTING: University hospital. SUBJECTS AND METHODS: A retrospective review of sinonasal outcomes was conducted for 30 AERD patients undergoing aspirin desensitization and maintenance therapy following ESS. Sinonasal outcomes were prospectively assessed by the Sinonasal Outcomes Test-22 (SNOT-22) and endoscopic polyp grading system. Data were collected preoperatively, 1 and 4 weeks postsurgery (before desensitization), and 1, 6, 12, 18, 24, and 30 months after aspirin desensitization. RESULTS: Twenty-eight of 30 patients (93.3%) successfully completed aspirin desensitization, whereas 2 of 30 (6.7%) were unable to complete desensitization due to respiratory intolerance. Of the 21 patients who successfully completed a minimum of 24 weeks of follow-up, 20 (95.2%) patients demonstrated sustained endoscopic and symptomatic improvement for a median follow-up period of 33 months. After surgical treatment but before desensitization, patients experienced significant reductions in SNOT-22 and polyp grade scores. In the first 6 months after aspirin desensitization, patients experienced further significant reductions in SNOT-22 scores, whereas polyp grade remained stable. The improvements in symptom endoscopic scores were preserved throughout the follow-up period after desensitization. No patients required additional sinus surgery. One patient had to discontinue aspirin therapy due to gastrointestinal side effects. No other adverse reactions to aspirin were noted. CONCLUSION: Aspirin desensitization following ESS appears to be a well-tolerated and effective adjunctive therapy for long-term control of nasal polyposis in patients with AERD. PMID- 25118196 TI - Rapid identification of a novel complex I MT-ND3 m.10134C>A mutation in a Leigh syndrome patient. AB - Leigh syndrome (LS) is a rare progressive multi-system neurodegenerative disorder, the genetics of which is frequently difficult to resolve. Rapid determination of the genetic etiology of LS in a 5-year-old girl facilitated inclusion in Edison Pharmaceutical's phase 2B clinical trial of EPI-743. SNP arrays and high-coverage whole exome sequencing were performed on the proband, both parents and three unaffected siblings. Subsequent multi-tissue targeted high depth mitochondrial sequencing was performed using custom long-range PCR amplicons. Tissue-specific mutant load was also assessed by qPCR. Complex I was interrogated by spectrophotometric enzyme assays and Western Blot. No putatively causal mutations were identified in nuclear-encoded genes. Analysis of low coverage off-target mitochondrial reads revealed a previously unreported mitochondrial mutation in the proband in MT-ND3 (m.10134C>A, p.Q26K), a Complex I mitochondrial gene previously associated with LS. Targeted investigations demonstrated that this mutation was 1% heteroplasmic in the mother's blood and homoplasmic in the proband's blood, fibroblasts, liver and muscle. Enzyme assays revealed decreased Complex I activity. The identification of this novel LS MT-ND3 variant, the genomics of which was accomplished in less than 3.5 weeks, indicates that rapid genomic approaches may prove useful in time-sensitive cases with an unresolved genetic diagnosis. PMID- 25118198 TI - Features of an alternative hemodialysis method using a hemoconcentrator during cardiopulmonary bypass surgeries. AB - PURPOSE: This study clarified the features of a hemoconcentrator-based, alternative hemodialysis (ALTHD) method that improves the speed of serum potassium (K(+)) concentration adjustments, compared with dilutional ultrafiltration (DUF), during cardiopulmonary bypasses. METHODS: Standardized bovine blood was recirculated (300 ml/min) through an in vitro hemoconcentrator circuit; hematocrit, K(+) and glucose levels were measured at 5-20 min after DUF or ALTHD. We evaluated DUF at dialysis speeds of 50-250 ml/min and ALTHD at speeds of 50-1000 ml/min. RESULTS: ALTHD rapidly corrected K(+) and glucose concentrations at speeds up to 800 ml/min. ALTHD took 8.9 min to reach a K(+) level of 4.5 mmol/L, faster than DUF (12.8 min). The ALTHD efficiency curves plateaued at 600 ml/min. CONCLUSION: ALTHD allowed faster adjustment of electrolyte levels, with peak efficiency at 600 ml/min. ALTHD has possible clinical application if available for potential use during all cardiopulmonary bypass surgeries involving extracorporeal circulation. PMID- 25118197 TI - What is the incidence of patients with palliative care needs presenting to the Emergency Department? a critical review. AB - BACKGROUND: Given the context of ageing populations globally, there are a growing number of patients with chronic conditions, some of whom are in the final stages of their disease trajectory, presenting to Emergency Departments. AIM: The aim was to estimate the incidence of patients with palliative care needs presenting to the department. METHODS: Three databases (MEDLINE, CINAHL and Embase) were systematically searched up to August 2012. The reference lists of included articles were searched as well as Google and Google Scholar. Only studies in English were included. Two reviewers independently reviewed studies at the abstract and full-body stages. A critical review using systematic methods was undertaken as statistical analysis could not be done because of a lack of information. RESULTS: Only 10 of 1427 identified records met the inclusion criteria. Different definitions of palliative care were evident. One article provided an incidence density for patients with non-small cell lung cancer, and we calculated the mean presentations to be 52.5 per 100 person-months. Two articles focussed on patients known to palliative care services; we estimated that 2.5 in 1000 Emergency Department visits were made by these patients. The review demonstrated that the studies were so different it was not possible to compare the data. CONCLUSION: There is an absence of evidence regarding the incidence of patients with palliative care needs presenting to the Emergency Department. Further research needs to be undertaken in this area to ensure both clinicians and policymakers have sufficient information for service provision. PMID- 25118200 TI - Increasing health examination survey participation rates by SMS reminders and flexible examination times. AB - AIMS: Declining participation rates are an increasing problem in population surveys. Different kinds of methods have been used to ensure participation rates as high as possible. Monetary incentives and reminders have been found to be effective ways to increase participation rates, but these are rather expensive to implement in large population surveys. There is a need for cheaper ways to motivate survey invitees to participate. METHODS: The Kuusamo Health Examination Survey was conducted in May-June 2011. A random sample of 250 people was selected for the survey. Mobile phone numbers, when available, were obtained for people within the sample. For a random sample of 50% of survey invitees with a mobile phone number, a short message service (SMS) reminder was sent prior to their appointment. All survey participants were asked to fill in a feedback questionnaire. RESULTS: Participation rate was 58% for men and 74% for women. Mobile phone numbers were available for 66% of the sample. Among those receiving an SMS reminder about their appointment, participation rates were up to 25 percentage points higher than among the group not receiving a reminder. In the feedback questionnaire, 9% of the survey participants reported that they would not have participated without the SMS reminder they received. Participants preferred morning hours and Monday-Tuesday as time and day options for the examinations. CONCLUSIONS: SMS reminder about the appointment time was an effective way to increase participation rate, especially among the youngest age groups also, providing flexible office hours for the examination clinic may increase participation rate. PMID- 25118199 TI - The relationship of green space, depressive symptoms and perceived general health in urban population. AB - AIMS: To assess the relationship between green space proximity, use of green space and depressive symptoms and perceived general health among a random sample men and women. METHODS: Cross-sectional study of a population-based sample of 6,944 45-72 year old Kaunas city residents. Self-reported questionnaires provided information on sociodemographic variables, health behaviours, depressive symptoms and poor and very poor perceived general health. Residential proximity to green spaces was defined as living less than 300 m, within interval of 300-999 m, and equal or more than 1 km from a park. The use of the park was divided into two categories: no park use or use <4hrs/week and use of the park >=4 h/week. The study received approval from the Kaunas Regional Research Ethics Committee. Multiple logistic regression assessed the associations controlling for confounding variables. RESULTS: The prevalence of depressive symptoms and poor and or very poor perceived general health was higher in women than in men. The association between the use of the park and residential proximity to the park revealed that women living >300 m from a green space and who used the space >=4 h/week showed higher odds 1.92 (1.11-3.3) and 1.68 (0.81-3.48) of depressive symptoms and poor and very poor perceived general health as compared to those who used the park <4 hrs/week and residential proximity was >300 m. CONCLUSIONS: The results of our study confirmed an association between use of the green space, residential proximity, and depressive symptoms and poor and very poor perceived general health among women only. PMID- 25118202 TI - Endoscopy-Assisted Total Mastectomy Followed by Immediate Pedicled Transverse Rectus Abdominis Musculocutaneous (TRAM) Flap Reconstruction: Preliminary Results of 48 Patients. AB - BACKGROUND: Endoscopy-assisted breast surgery performed through minimal axillary and/or periareolar incisions is a viable option for patients with breast cancer. In this study, we report the preliminary results of patients with breast cancer who underwent endoscopy-assisted total mastectomy (EATM) followed immediately by pedicled transverse abdominis musculocutaneous (TRAM) flap reconstruction. METHODS: Patients in this study comprised women with breast cancer who received EATM and pedicled TRAM flap reconstruction. Clinicopathologic characteristics, type of surgery, complications, and rate of recurrence were recorded. The cosmetic outcomes were evaluated objectively by the surgeons and subjectively by the patients at 3-month postoperative follow-up. RESULTS: A total of 48 patients underwent 49 EATM procedures followed by pedicled TRAM flap reconstruction. Of them, 79.6% underwent endoscopic-assisted nipple-sparing mastectomy and 20.4% received endoscopic-assisted skin-sparing mastectomy. The types of cancer among these patients included ductal carcinoma in situ in 34.7%, stage I cancer in 36.7%, stage II cancer in 24.5%, and stage IIIa cancer in 4.1% patients. Mean tumor size was 2.1 +/- 1.4 cm. There were no cases of flap failure. Partial nipple areolar complex ischemia/necrosis occurred in 4 (10.3%) patients; however, all cases resolved after conservative treatment. In the aesthetic outcome evaluation, EATM + TRAM were associated with 89.8% good, 8.2% fair, and 2% unsatisfactory result. No local recurrence was observed during the follow-up period. CONCLUSION: EATM followed immediately by pedicled TRAM flap reconstruction is a safe procedure and results in good cosmetic outcome in women with early-stage breast cancer. PMID- 25118204 TI - Back to the basis: breast cancer heterogeneity from an etiological perspective. PMID- 25118205 TI - Motion sickness in migraine and vestibular disorders. PMID- 25118206 TI - A diagnostic flow chart for POLG-related diseases based on signs sensitivity and specificity. AB - OBJECTIVE: Diseases due to mutations of POLG gene, encoding the mitochondrial DNA polymerase, are reputed to have very diverse clinical presentations and have been proposed to cause up to 25% adult mitochondrial diseases. Our objective was the evaluation of the specificity and sensitivity of the signs encountered with POLG mutations. DESIGN: Forty-four patients out of 154 with sequenced POLG gene had mutations affecting either one (POLG(+/-) group) or two POLG alleles (POLG(+/+) group). Phenotyping included clinical signs, electroneuromyography and brain imaging while mitochondrial investigations encompassed muscle histochemistry, respiratory chain assays and search for multiple mitochondrial deletions. The specificity and sensitivity of the signs associated with POLG mutations were analysed by comparison between POLG(+/+) and patients without POLG mutation. RESULTS: High sensitivity but low specificity was observed with single signs such as axonal sensory neuropathy, cerebellar syndrome, movement disorders and weakness involving ocular, pharyngeal, axial and/or limb muscles. Specificity was increased with combination of previous signs plus psychiatric symptoms, cognitive impairment and epilepsy. High specificity and sensitivity was only obtained with sensory neuronopathy associated with one of the following signs: weakness of ocular, pharyngeal, axial and/or limb muscles. Mitochondrial investigations did not suffice for diagnosis. The widespread neuromuscular signs were often present since disease onset and were the rule above 50 years of age leading to a very low probability of POLG mutations in patients with less than three signs and absent sensory neuropathy. CONCLUSIONS: Phenotypes associated with POLG mutations follow a reproducible pattern, which allows establishing a diagnostic flow chart. PMID- 25118208 TI - Simple prognostic model for patients with advanced cancer based on performance status. AB - PURPOSE: Providing survival estimates is important for decision making in oncology care. The purpose of this study was to provide survival estimates for outpatients with advanced cancer, using the Eastern Cooperative Oncology Group (ECOG), Palliative Performance Scale (PPS), and Karnofsky Performance Status (KPS) scales, and to compare their ability to predict survival. METHODS: ECOG, PPS, and KPS were completed by physicians for each new patient attending the Princess Margaret Cancer Centre outpatient Oncology Palliative Care Clinic (OPCC) from April 2007 to February 2010. Survival analysis was performed using the Kaplan-Meier method. The log-rank test for trend was employed to test for differences in survival curves for each level of performance status (PS), and the concordance index (C-statistic) was used to test the predictive discriminatory ability of each PS measure. RESULTS: Measures were completed for 1,655 patients. PS delineated survival well for all three scales according to the log-rank test for trend (P < .001). Survival was approximately halved for each worsening performance level. Median survival times, in days, for each ECOG level were: EGOG 0, 293; ECOG 1, 197; ECOG 2, 104; ECOG 3, 55; and ECOG 4, 25.5. Median survival times, in days, for PPS (and KPS) were: PPS/KPS 80-100, 221 (215); PPS/KPS 60 to 70, 115 (119); PPS/KPS 40 to 50, 51 (49); PPS/KPS 10 to 30, 22 (29). The C statistic was similar for all three scales and ranged from 0.63 to 0.64. CONCLUSION: We present a simple tool that uses PS alone to prognosticate in advanced cancer, and has similar discriminatory ability to more complex models. PMID- 25118209 TI - Cancer survivors: a look backward and forward. PMID- 25118203 TI - How many etiological subtypes of breast cancer: two, three, four, or more? AB - Breast cancer is a heterogeneous disease, divisible into a variable number of clinical subtypes. A fundamental question is how many etiological classes underlie the clinical spectrum of breast cancer? An etiological subtype reflects a grouping with a common set of causes, whereas a clinical subtype represents a grouping with similar prognosis and/or prediction. Herein, we review the evidence for breast cancer etiological heterogeneity. We then evaluate the etiological evidence with mRNA profiling data. A bimodal age distribution at diagnosis with peak frequencies near ages 50 and 70 years is a fundamental characteristic of breast cancer for important tumor features, clinical characteristics, risk factor profiles, and molecular subtypes. The bimodal peak frequencies at diagnosis divide breast cancer overall into a "mixture" of two main components in varying proportions in different cancer populations. The first breast cancer tends to arise early in life with modal age-at-diagnosis near 50 years and generally behaves aggressively. The second breast cancer occurs later in life with modal age near 70 years and usually portends a more indolent clinical course. These epidemiological and molecular data are consistent with a two-component mixture model and compatible with a hierarchal view of breast cancers arising from two main cell types of origin. Notwithstanding the potential added value of more detailed categorizations for personalized breast cancer treatment, we suggest that the development of better criteria to identify the two proposed etiologic classes would advance breast cancer research and prevention. PMID- 25118210 TI - Pioneering quality assessment in European cancer centers: a data analysis of the organization for European cancer institutes accreditation and designation program. AB - PURPOSE: In order to improve the quality of care in Cancer Centers (CC) and designate Comprehensive Cancer Centers (CCCs), the Organization for European Cancer Institutes (OECI) launched an Accreditation and Designation (A&D) program. The program facilitates the collection of defined data and the assessment of cancer center quality. This study analyzes the results of the first 10 European centers that entered the program. METHODS: The assessment included 927 items divided across qualitative and quantitative questionnaires. Data collected during self-assessment and peer-review from the 10 first participating centers were combined in a database for comparative analysis using simple statistics. Quantitative and qualitative results were validated by auditors during the peer review visits. RESULTS: Volumes of various functions and activities dedicated to care, research, and education varied widely among centers. There were no significant differences in resources for radiology, radiotherapy, pathologic diagnostic, and surgery. Differences were observed in the use of clinical pathways but not for the practices of holding multidisciplinary team meetings and conforming to guidelines. Regarding human resources, main differences were in the composition and number of supportive care and research staff. All 10 centers applied as CCCs; five obtained the label, and five were designated as CCs. CONCLUSION: The OECI A&D program allows comparisons between centers with regard to management, research, care, education, and designation as CCs or CCCs. Through the peer review system, recommendations for improvements are given. Assessing the added value of the program, as well as research and patient treatment outcomes, is the next step. PMID- 25118207 TI - 20 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors. AB - The association between leptin and reproduction originated with the leptin mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin-responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B, and dynorphin and these could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that agouti-related protein/neuropeptide Y neurons project onto GnRH and kisspeptin neurons, allowing for a crosstalk between food intake and reproduction. Finally, while puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. The mechanisms underlying leptin resistance in pregnancy have lagged; however, the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the following decade to shed new light on these complex and essential pathways. PMID- 25118216 TI - Development of an anti-claudin-3 and -4 bispecific monoclonal antibody for cancer diagnosis and therapy. AB - Most malignant tumors are derived from epithelium, and claudin (CLDN)-3 and CLDN 4 are frequently overexpressed in such tumors. Although antibodies have potential in cancer diagnostics and therapy, development of antibodies against CLDNs has been difficult because the extracellular domains of CLDNs are too small and there is high homology among human, rat, and mouse sequences. Here, we created a monoclonal antibody that recognizes human CLDN-3 and CLDN-4 by immunizing rats with a plasmid vector encoding human CLDN-4. A hybridoma clone that produced a rat monoclonal antibody recognizing both CLDN-3 and -4 (clone 5A5) was obtained from a hybridoma screen by using CLDN-3- and -4-expressing cells; 5A5 did not bind to CLDN-1-, -2-, -5-, -6-, -7-, or -9-expressing cells. Fluorescence conjugated 5A5 injected into xenograft mice bearing human cancer MKN74 or LoVo cells could visualize the tumor cells. The human-rat chimeric IgG1 monoclonal antibody (xi5A5) activated FcgammaRIIIa in the presence of CLDN-3- or -4 expressing cells, indicating that xi5A5 may exert antibody-dependent cellular cytotoxicity. Administration of xi5A5 attenuated tumor growth in xenograft mice bearing MKN74 or LoVo cells. These results suggest that 5A5 shows promise in the development of a diagnostic and therapeutic antibody for cancers. PMID- 25118217 TI - Modulation of resistance artery tone by the trace amine beta-phenylethylamine: dual indirect sympathomimetic and alpha1-adrenoceptor blocking actions. AB - The trace amine beta-phenylethylamine (PEA) is normally present in the body at low nanomolar concentrations but can reach micromolar levels after ingestion of drugs that inhibit monoamine oxidase and primary amine oxidase. In vivo, PEA elicits a robust pressor response, but there is no consensus regarding the underlying mechanism, with both vasodilation and constriction reported in isolated blood vessels. Using functional and biochemical approaches, we found that at low micromolar concentrations PEA (1-30 MUM) enhanced nerve-evoked vasoconstriction in the perfused rat mesenteric bed but at a higher concentration (100 MUM) significantly inhibited these responses. The alpha2-adrenoceptor antagonist rauwolscine (1 uM) also enhanced nerve-mediated vasoconstriction, but in the presence of both rauwolscine (1 uM) and PEA (30 uM) together, nerve-evoked responses were initially potentiated and then showed time-dependent rundown. PEA (10 and 100 MUM) significantly increased noradrenaline outflow from the mesenteric bed as determined by high-pressure liquid chromatography coupled with electrochemical detection. In isolated endothelium-denuded arterial segments, PEA (1 uM to 1 mM) caused concentration-dependent reversal of tone elicited by the alpha1-adrenoceptor agonists noradrenaline (EC50 51.69 +/- 10.8 MUM; n = 5), methoxamine (EC50 68.21 +/- 1.70 MUM; n = 5), and phenylephrine (EC50 67.74 +/- 16.72 MUM; n = 5) but was ineffective against tone induced by prostaglandin F2 alpha or U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F2 alpha). In rat brain homogenates, PEA displaced binding of both [(3)H]prazosin (Ki ~ 25 MUM) and [(3)H]rauwolscine (Ki ~ 1.2 MUM), ligands for alpha1- and alpha2 adrenoceptors, respectively. These data provide the first demonstration that dual indirect sympathomimetic and alpha1-adrenoceptor blocking actions underlie the vascular effects of PEA in resistance arteries. PMID- 25118218 TI - Views and experiences of the NHS Health Check provided by general medical practices: cross-sectional survey in high-risk patients. AB - BACKGROUND: Since the NHS Health Check programme was initiated in 2009, no survey has sought patients' views of Checks provided by GP practices and few studies have reported views of the wider public. This study sought the views and experiences of patients with potentially high-cardiovascular disease (CVD) risk. METHODS: Cross-sectional postal survey of all the patients with an actual or estimated CVD risk score of at least 20% over 10 years, registered with 16 general practices in Sefton, North West England, with no follow-up. RESULTS: The response rate was 23.4% (644/2958), 67.4% had attended and 73.8% of those not yet invited indicated willingness to attend. Both groups had positive views towards Health Checks, but more non-attenders agreed these should only be performed by doctors. Attenders had better self-reported health and healthy lifestyle than non attenders. Overall 86.6% of attenders recalled receiving one or more pieces of lifestyle advice and 71.0% claimed to have made at least one lifestyle change; however, perception and understanding of CVD risk appeared limited. CONCLUSION: Both attenders and non-attenders had positive views towards NHS Health Checks in general practice and resultant self-reported lifestyle change in attenders was high. Clearer written information and explanation of personal CVD risk are required. PMID- 25118220 TI - Accidental diagnosis: Aeromonas infection leading to discovery of acute myeloid leukemia with meylodysplastic syndrome. AB - PATIENT: 47-year-old African American man. CHIEF COMPLAINT: Initially, serious finger abscess. The patient reported severe pain that was localized to that finger only. HISTORY OF PRESENT ILLNESS: His finger had become sore and then progressively more painful and swollen. PAST MEDICAL HISTORY: A few weeks earlier, the patient had had a similar abscess on his leg; he could not recall any specific injuries other than this. He had a past history of epilepsy that is totally unrelated to this case; he had not had any episodes in more than 10 years. Otherwise, the medical history of the patient was relatively healthy: he is a nonsmoker with no history of diabetes or steroid use. SOCIAL HISTORY: Patient washed cars for a living. FAMILY HISTORY: Noncontributory. PHYSICAL EXAMINATION: Initially, the patient was sent home with a course of antibiotics (cephalexin and trimethoprim/sulfamethoxazole) and was asked to return to the hospital for follow up within two days. By the time of the follow-up visit, the antibiotic treatment had been unsuccessful, and the patient experienced more pain in the finger; the flesh of the finger was becoming black and necrotic. The patient tested positive for all myeloid markers: myeloperoxidase (MPO), CD34, CD33, CD13, CD45, human leukocyte antigen-DR subregion (HLA-DR), CD15, and CD11c. Trilinear dysplasia was indicated by the results of bone-marrow studies and peripheral blood smear testing. PMID- 25118219 TI - Smoking patterns in Great Britain: the rise of cheap cigarette brands and roll your own (RYO) tobacco. AB - BACKGROUND: In Britain, the tobacco industry segments cigarettes into four price categories-premium, mid-price, economy and ultra-low-price (ULP). Our previous work shows that tobacco companies have kept ULP prices stable in real terms. Roll your own (RYO) tobacco remains cheaper still. METHODS: Analysis of 2001-08 General Household Survey data to examine trends in use of these cheap products and, using logistic regression, the profile of users of these products. RESULTS: Among smokers, the proportion using cheap products (economy, ULP and RYO combined) increased significantly in almost all age groups and geographic areas. Increases were most marked in under 24 year olds, 76% of whom smoked cheap cigarettes by 2008. All cheap products were more commonly used in lower socio economic groups. Men and younger smokers were more likely to smoke RYO while women smoked economy brands. Smokers outside London and the South East of England were more likely to smoke some form of cheap tobacco even once socio-economic differences were accounted for. CONCLUSIONS: This paper demonstrates that cheap tobacco use is increasing among young and disadvantaged smokers compromising declines in population smoking prevalence. Thus, tobacco industry pricing appears to play a key role in explaining smoking patterns and inequalities in smoking. PMID- 25118225 TI - The PROMIS smoking assessment toolkit--background and introduction to supplement. AB - INTRODUCTION: The PROMIS Smoking Initiative has developed an assessment toolkit for measuring 6 domains of interest to cigarette smoking research: nicotine dependence, coping expectancies, emotional and sensory expectancies, health expectancies, psychosocial expectancies, and social motivations for smoking. The papers in this supplement describe the methods used to develop these item banks, their psychometric properties, and the preliminary evidence for their validity. This commentary is meant to provide background information for the material in this supplement. METHODS: After discussing the use of item response theory in behavioral measurement, I will briefly review the initial developmental steps for the smoking assessment toolkit. Finally, I will describe the contents of this supplement and provide some closing remarks. RESULTS: Psychometric evidence strongly supports the utility of the toolkit of item banks, short forms (SFs), and computer adaptive tests (CATs). The item banks for daily smokers produce scores with reliability estimates above 0.90 for a wide range of each cigarette smoking domain continuum, and SF and CAT administrations also achieve high reliability (generally greater than 0.85) using very few items (4-7 items for most banks). Performance of the banks for nondaily smokers is similar. Preliminary evidence supports the concurrent and the discriminant validity of the bank domains. CONCLUSIONS: The new smoking assessment toolkit has attractive measurement features that are likely to benefit smoking research as researchers begin to utilize this resource. Information about the toolkit and access to the assessments is available at the project Web site (http://www.rand.org/health/projects/promis-smoking-initiative.html) and can also be accessed via the PROMIS Assessment Center (www.assessmentcenter.net). PMID- 25118226 TI - Development of the PROMIS nicotine dependence item banks. AB - INTRODUCTION: Nicotine dependence is a core construct important for understanding cigarette smoking and smoking cessation behavior. This article describes analyses conducted to develop and evaluate item banks for assessing nicotine dependence among daily and nondaily smokers. METHODS: Using data from a sample of daily (N = 4,201) and nondaily (N =1,183) smokers, we conducted a series of item factor analyses, item response theory analyses, and differential item functioning analyses (according to gender, age, and race/ethnicity) to arrive at a unidimensional set of nicotine dependence items for daily and nondaily smokers. We also evaluated performance of short forms (SFs) and computer adaptive tests (CATs) to efficiently assess dependence. RESULTS: A total of 32 items were included in the Nicotine Dependence item banks; 22 items are common across daily and nondaily smokers, 5 are unique to daily smokers, and 5 are unique to nondaily smokers. For both daily and nondaily smokers, the Nicotine Dependence item banks are strongly unidimensional, highly reliable (reliability = 0.97 and 0.97, respectively), and perform similarly across gender, age, and race/ethnicity groups. SFs common to daily and nondaily smokers consist of 8 and 4 items (reliability = 0.91 and 0.81, respectively). Results from simulated CATs showed that dependence can be assessed with very good precision for most respondents using fewer than 6 items adaptively selected from the item banks. CONCLUSIONS: Nicotine dependence on cigarettes can be assessed on the basis of these item banks via one of the SFs, by using CATs, or through a tailored set of items selected for a specific research purpose. PMID- 25118227 TI - Development of the PROMIS coping expectancies of smoking item banks. AB - OBJECTIVE: Smoking is a coping strategy for many smokers who then have difficulty finding new ways to cope with negative affect when they quit. This paper describes analyses conducted to develop and evaluate item banks for assessing the coping expectancies of smoking for daily and nondaily smokers. METHODS: Using data from a large sample of daily (N = 4,201) and nondaily (N = 1,183) smokers, we conducted a series of item factor analyses, item response theory analyses, and differential item functioning (DIF) analyses (according to gender, age, and ethnicity) to arrive at a unidimensional set of items for daily and nondaily smokers. We also evaluated performance of short forms (SFs) and computer adaptive tests (CATs) for assessing coping expectancies of smoking. RESULTS: For both daily and nondaily smokers, the unidimensional Coping Expectancies item banks (21 items) are relatively DIF free and are highly reliable (0.96 and 0.97, respectively). A common 4-item SF for daily and nondaily smokers also showed good reliability (0.85). Adaptive tests required an average of 4.3 and 3.7 items for simulated daily and nondaily respondents, respectively, and achieved reliabilities of 0.91 for both when the maximum test length was 10 items. CONCLUSIONS: This research provides a new set of items that can be used to reliably assess coping expectancies of smoking, through a SF, CAT, or a tailored set selected for a specific research purpose. PMID- 25118228 TI - Development of the PROMIS positive emotional and sensory expectancies of smoking item banks. AB - INTRODUCTION: The positive emotional and sensory expectancies of cigarette smoking include improved cognitive abilities, positive affective states, and pleasurable sensorimotor sensations. This paper describes development of Positive Emotional and Sensory Expectancies of Smoking item banks that will serve to standardize the assessment of this construct among daily and nondaily cigarette smokers. METHODS: Data came from daily (N = 4,201) and nondaily (N =1,183) smokers who completed an online survey. To identify a unidimensional set of items, we conducted item factor analyses, item response theory analyses, and differential item functioning analyses. Additionally, we evaluated the performance of fixed-item short forms (SFs) and computer adaptive tests (CATs) to efficiently assess the construct. RESULTS: Eighteen items were included in the item banks (15 common across daily and nondaily smokers, 1 unique to daily, 2 unique to nondaily). The item banks are strongly unidimensional, highly reliable (reliability = 0.95 for both), and perform similarly across gender, age, and race/ethnicity groups. A SF common to daily and nondaily smokers consists of 6 items (reliability = 0.86). Results from simulated CATs indicated that, on average, less than 8 items are needed to assess the construct with adequate precision using the item banks. CONCLUSIONS: These analyses identified a new set of items that can assess the positive emotional and sensory expectancies of smoking in a reliable and standardized manner. Considerable efficiency in assessing this construct can be achieved by using the item bank SF, employing computer adaptive tests, or selecting subsets of items tailored to specific research or clinical purposes. PMID- 25118229 TI - Development of the PROMIS health expectancies of smoking item banks. AB - INTRODUCTION: Smokers' health-related outcome expectancies are associated with a number of important constructs in smoking research, yet there are no measures currently available that focus exclusively on this domain. This paper describes the development and evaluation of item banks for assessing the health expectancies of smoking. METHODS: Using data from a sample of daily (N = 4,201) and nondaily (N = 1,183) smokers, we conducted a series of item factor analyses, item response theory analyses, and differential item functioning analyses (according to gender, age, and race/ethnicity) to arrive at a unidimensional set of health expectancies items for daily and nondaily smokers. We also evaluated the performance of short forms (SFs) and computer adaptive tests (CATs) to efficiently assess health expectancies. RESULTS: A total of 24 items were included in the Health Expectancies item banks; 13 items are common across daily and nondaily smokers, 6 are unique to daily, and 5 are unique to nondaily. For both daily and nondaily smokers, the Health Expectancies item banks are unidimensional, reliable (reliability = 0.95 and 0.96, respectively), and perform similarly across gender, age, and race/ethnicity groups. A SF common to daily and nondaily smokers consists of 6 items (reliability = 0.87). Results from simulated CATs showed that health expectancies can be assessed with good precision with an average of 5-6 items adaptively selected from the item banks. CONCLUSIONS: Health expectancies of smoking can be assessed on the basis of these item banks via SFs, CATs, or through a tailored set of items selected for a specific research purpose. PMID- 25118230 TI - Development of the PROMIS negative psychosocial expectancies of smoking item banks. AB - INTRODUCTION: Negative psychosocial expectancies of smoking include aspects of social disapproval and disappointment in oneself. This paper describes analyses conducted to develop and evaluate item banks for assessing psychosocial expectancies among daily and nondaily smokers. METHODS: Using data from a sample of daily (N = 4,201) and nondaily (N =1,183) smokers, we conducted a series of item factor analyses, item response theory analyses, and differential item functioning analyses (according to gender, age, and race/ethnicity) to arrive at a unidimensional set of psychosocial expectancies items for daily and nondaily smokers. We also evaluated performance of short forms (SFs) and computer adaptive tests (CATs) to efficiently assess psychosocial expectancies. RESULTS: A total of 21 items were included in the Psychosocial Expectancies item banks: 14 items are common across daily and nondaily smokers, 6 are unique to daily, and 1 is unique to nondaily. For both daily and nondaily smokers, the Psychosocial Expectancies item banks are strongly unidimensional, highly reliable (reliability = 0.95 and 0.93, respectively), and perform similarly across gender, age, and race/ethnicity groups. A SF common to daily and nondaily smokers consists of 6 items (reliability = 0.85). Results from simulated CATs showed that, on average, fewer than 8 items are needed to assess psychosocial expectancies with adequate precision when using the item banks. CONCLUSIONS: Psychosocial expectancies of smoking can be assessed on the basis of these item banks via the SF, by using CAT, or through a tailored set of items selected for a specific research purpose. PMID- 25118233 TI - Delivering on its promises: the PROMIS Smoking Initiative item banks. PMID- 25118231 TI - Development of the PROMIS Social Motivations for Smoking item banks. AB - INTRODUCTION: Smoking behavior is influenced by social motivations such as the expected social benefits of smoking and the social cues that induce craving. This paper describes development of the PROMIS Social Motivations for Smoking item banks, which will serve to standardize assessment of these social motivations among daily and nondaily smokers. METHODS: Daily (N = 4,201) and nondaily (N =1,183) smokers completed an online survey. Item factor analyses, item response theory analyses, and differential item functioning analyses were conducted to identify a unidimensional set of items for each group. Short forms (SFs) and computer adaptive tests (CATs) were evaluated as tools for more efficiently assessing this construct. RESULTS: A total of 15 items were included in the item banks (9 items common to daily and nondaily smokers, 3 unique to daily, 3 unique to nondaily). Scores based on full item banks are highly reliable (reliability = 0.90-0.91). Additionally, the item banks are strongly unidimensional and perform similarly across gender, age, and race/ethnicity groups. A fixed SF for use with both daily and nondaily smokers consists of 4 items (reliability = 0.80). Results from simulated CATs showed that, on average, fewer than 5 items are needed to assess this construct with adequate precision using the item banks. CONCLUSIONS: A new set of items has been identified for assessing the social motivations for smoking in a reliable, standardized manner for daily and nondaily smokers. In addition to using the full item banks, efficient assessment can be achieved by using SFs, employing CATs, or selecting items tailored to specific research or clinical purposes. PMID- 25118232 TI - The PROMIS Smoking Initiative: initial validity evidence for six new smoking item banks. AB - INTRODUCTION: The Patient-Reported Outcomes Measurement Information System (PROMIS) Smoking Initiative has developed 6 item banks for assessing smoking behaviors and biopsychosocial correlates of smoking among daily and nondaily adult cigarette smokers. This paper presents descriptive information and preliminary validity evidence for the item banks (Nicotine Dependence, Coping Expectancies, Emotional and Sensory Expectancies, Health Expectancies, Psychosocial Expectancies, and Social Motivations). METHODS: Using data from a large sample of daily (N = 4,201) and nondaily (N = 1,183) smokers, we generated mean daily and nondaily smoking bank scores according to select demographic groups. We also examined correlations among the 6 banks and examined the associations of bank scores with smoking behavior items (e.g., quantity of smoking, interest in quitting) and select health-related quality of life measures (i.e., physical functioning, anxiety, alcohol consumption). RESULTS: Correlations among the 6 banks are moderate (daily mean r = .48, range = .04-.80; nondaily mean r = .47, range = .12-.75). The pattern of associations between bank scores and other measures provides validity evidence for the bank domains (e.g., nicotine dependence is most strongly associated with smoking quantity and time to first cigarette of the day; health and psychosocial expectancies are most related to quitting recency and interest; coping expectancies are strongly associated with anxiety). CONCLUSIONS: These analyses provide useful descriptive information about the 6 smoking item banks as well as preliminary evidence for their validity. Independent sample data are currently being collected to replicate these findings, to establish test-retest reliability, and to develop crosswalks to existing smoking measures (e.g., nicotine dependence to Fagerstrom Test for Nicotine Dependence). Future research will also evaluate the bank scores' sensitivity to change. PMID- 25118234 TI - Essentiality of succinate dehydrogenase in Mycobacterium smegmatis and its role in the generation of the membrane potential under hypoxia. AB - Succinate:quinone oxidoreductase (Sdh) is a membrane-bound complex that couples the oxidation of succinate to fumarate in the cytoplasm to the reduction of quinone to quinol in the membrane. Mycobacterial species harbor genes for two putative sdh operons, but the individual roles of these two operons are unknown. In this communication, we show that Mycobacterium smegmatis mc(2)155 expresses two succinate dehydrogenases designated Sdh1 and Sdh2. Sdh1 is encoded by a five gene operon (MSMEG_0416-MSMEG_0420), and Sdh2 is encoded by a four-gene operon (MSMEG_1672-MSMEG_1669). These two operons are differentially expressed in response to carbon limitation, hypoxia, and fumarate, as monitored by sdh promoter-lacZ fusions. While deletion of the sdh1 operon did not yield any growth phenotypes on succinate or other nonfermentable carbon sources, the sdh2 operon could be deleted only in a merodiploid background, demonstrating that Sdh2 is essential for growth. Sdh activity and succinate-dependent proton pumping were detected in cells grown aerobically, as well as under hypoxia. Fumarate reductase activity was absent under these conditions, indicating that neither Sdh1 nor Sdh2 could catalyze the reverse reaction. Sdh activity was inhibited by the Sdh inhibitor 3-nitroproprionate (3NP), and treatment with 3NP dissipated the membrane potential of wild-type or Deltasdh1 mutant cells under hypoxia but not that of cells grown aerobically. These data imply that Sdh2 is the generator of the membrane potential under hypoxia, an essential role for the cell. IMPORTANCE: Complex II or succinate dehydrogenase (Sdh) is a major respiratory enzyme that couples the oxidation of succinate to fumarate in the cytoplasm to the reduction of quinone to quinol in the membrane. Mycobacterial species harbor genes for two putative sdh operons, sdh1 and sdh2, but the individual roles of these two operons are unknown. In this communication, we show that sdh1 and sdh2 are differentially expressed in response to energy limitation, oxygen tension, and alternative electron acceptor availability, suggesting distinct functional cellular roles. Sdh2 was essential for growth and generation of the membrane potential in hypoxic cells. Given the essentiality of succinate dehydrogenase and oxidative phosphorylation in the growth cycle of Mycobacterium tuberculosis, the potential exists to develop new antituberculosis agents against the mycobacterial succinate dehydrogenase. This enzyme has been proposed as a potential target for the development of new chemotherapeutic agents against intracellular parasites and mitochondrion-associated disease. PMID- 25118235 TI - A new method to determine in vivo interactomes reveals binding of the Legionella pneumophila effector PieE to multiple rab GTPases. AB - Legionella pneumophila, the causative agent of Legionnaires' disease, uses the Dot/Icm type IV secretion system (T4SS) to translocate more than 300 effectors into host cells, where they subvert host cell signaling. The function and host cell targets of most effectors remain unknown. PieE is a 69-kDa Dot/Icm effector containing three coiled-coil (CC) regions and 2 transmembrane (TM) helices followed by a fourth CC region. Here, we report that PieE dimerized by an interaction between CC3 and CC4. We found that ectopically expressed PieE localized to the endoplasmic reticulum (ER) and induced the formation of organized smooth ER, while following infection PieE localized to the Legionella containing vacuole (LCV). To identify the physiological targets of PieE during infection, we established a new purification method for which we created an A549 cell line stably expressing the Escherichia coli biotin ligase BirA and infected the cells with L. pneumophila expressing PieE fused to a BirA-specific biotinylation site and a hexahistidine tag. Following tandem Ni(2+) nitrilotriacetic acid (NTA) and streptavidin affinity chromatography, the effector-target complexes were analyzed by mass spectrometry. This revealed interactions of PieE with multiple host cell proteins, including the Rab GTPases 1a, 1b, 2a, 5c, 6a, 7, and 10. Binding of the Rab GTPases, which was validated by yeast two-hybrid binding assays, was mediated by the PieE CC1 and CC2. In summary, using a novel, highly specific strategy to purify effector complexes from infected cells, which is widely applicable to other pathogens, we identified PieE as a multidomain LCV protein with promiscuous Rab GTPase-binding capacity. IMPORTANCE: The respiratory pathogen Legionella pneumophila uses the Dot/Icm type IV secretion system to translocate more than 300 effector proteins into host cells. The function of most effectors in infection remains unknown. One of the bottlenecks for their characterization is the identification of target proteins. Frequently used in vitro approaches are not applicable to all effectors and suffer from high rates of false positives or missed interactions, as they are not performed in the context of an infection. Here, we determine key functional domains of the effector PieE and describe a new method to identify host cell targets under physiological infection conditions. Our approach, which is applicable to other pathogens, uncovered the interaction of PieE with several proteins involved in membrane trafficking, in particular Rab GTPases, revealing new details of the Legionella infection strategy and demonstrating the potential of this method to greatly advance our understanding of the molecular basis of infection. PMID- 25118236 TI - Whole-animal chemical screen identifies colistin as a new immunomodulator that targets conserved pathways. AB - The purpose of this study was to take advantage of the nematode Caenorhabditis elegans to perform a whole-animal chemical screen to identify potential immune activators that may confer protection against bacterial infections. We identified 45 marketed drugs, out of 1,120 studied compounds, that are capable of activating a conserved p38/PMK-1 mitogen-activated protein kinase pathway required for innate immunity. One of these drugs, the last-resort antibiotic colistin, protected against infections by the Gram-negative pathogens Yersinia pestis and Pseudomonas aeruginosa but not by the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus. Protection was independent of the antibacterial activity of colistin, since the drug was administered prophylactically prior to the infections and it was also effective against antibiotic-resistant bacteria. Immune activation by colistin is mediated not only by the p38/PMK-1 pathway but also by the conserved FOXO transcription factor DAF 16 and the transcription factor SKN-1. Furthermore, p38/PMK-1 was found to be required in the intestine for immune activation by colistin. Enhanced p38/PMK-1 mediated immune responses by colistin did not reduce the bacterial burden, indicating that the pathway plays a role in the development of host tolerance to infections by Gram-negative bacteria. IMPORTANCE: The innate immune system represents the front line of our defenses against invading microorganisms. Given the ever-increasing resistance to antibiotics developed by bacterial pathogens, the possibility of boosting immune defenses represents an interesting, complementary approach to conventional antibiotic treatments. Here we report that the antibiotic colistin can protect against infections by a mechanism that is independent of its microbicidal activity. Prophylactic treatment with colistin activates a conserved p38/PMK-1 pathway in the intestine that helps the host better tolerate a bacterial infection. Since p38/PMK-1-mediated immune responses appear to be conserved from plants to mammals, colistin may also activate immunity in higher organisms, including humans. Antibiotics with immunomodulatory properties have the potential of improving the long-term outcome of patients with chronic infectious diseases. PMID- 25118237 TI - Influenza virus A/Anhui/1/2013 (H7N9) replicates efficiently in the upper and lower respiratory tracts of cynomolgus macaques. AB - In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277-2285, 2013, doi:10.1056/NEJMoa1305584). IMPORTANCE: Influenza A virus H7N9 emerged early in 2013, and human cases have continued to emerge since then. Although H7N9 virus-induced disease in humans is often very severe and even lethal, the majority of reported H7N9 cases occurred in older people and people with underlying medical conditions. To better understand the pathogenicity of this virus, healthy cynomolgus macaques were inoculated with influenza A virus H7N9. Cynomolgus macaques were used as a model because the receptor distribution for H7N9 virus in macaques was recently shown to be more similar to that in humans than that of other frequently used animal models. From comparison with previous studies, we conclude that the emerging H7N9 influenza virus was more pathogenic in cynomolgus macaques than seasonal influenza A viruses and most isolates of the pandemic H1N1 virus but less pathogenic than the 1918 Spanish influenza virus or highly pathogenic avian influenza (HPAI) H5N1 virus. PMID- 25118238 TI - Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. AB - The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ileal organoids. We have explored the transcriptional response of organoids upon exposure to short-chain fatty acids (SCFAs) and products generated by two abundant microbiota constituents, Akkermansia muciniphila and Faecalibacterium prausnitzii. We observed that A. muciniphila metabolites affect various transcription factors and genes involved in cellular lipid metabolism and growth, supporting previous in vivo findings. Contrastingly, F. prausnitzii products exerted only weak effects on host transcription. Additionally, A. muciniphila and its metabolite propionate modulated expression of Fiaf, Gpr43, histone deacetylases (HDACs), and peroxisome proliferator-activated receptor gamma (Ppargamma), important regulators of transcription factor regulation, cell cycle control, lipolysis, and satiety. This work illustrates that specific bacteria and their metabolites differentially modulate epithelial transcription in mouse organoids. We demonstrate that intestinal organoids provide a novel and powerful ex vivo model for host microbiome interaction studies. IMPORTANCE: We investigated the influence of the gut microbiota and microbially produced short-chain fatty acids (SCFAs) on gut functioning. Many commensal bacteria in the gut produce SCFAs, particularly butyrate, acetate, and propionate, which have been demonstrated to reduce the risk of gastrointestinal disorders. Organoids-small crypt-villus structures grown from ileal intestinal stem cells-were exposed to SCFAs and two specific gut bacteria. Akkermansia muciniphila, found in the intestinal mucus, was recently shown to have a favorable effect on the disrupted metabolism associated with obesity. Faecalibacterium prausnitzii is a commensal gut bacterium, the absence of which may be associated with Crohn's disease. We showed that in our model, A. muciniphila induces stronger effects on the host than F. prausnitzii. We observed that A. muciniphila and propionate affect the expression of genes involved in host lipid metabolism and epigenetic activation or silencing of gene expression. We demonstrated that organoids provide a powerful tool for host-microbe interaction studies. PMID- 25118239 TI - Glycan degradation (GlyDeR) analysis predicts mammalian gut microbiota abundance and host diet-specific adaptations. AB - Glycans form the primary nutritional source for microbes in the human gut, and understanding their metabolism is a critical yet understudied aspect of microbiome research. Here, we present a novel computational pipeline for modeling glycan degradation (GlyDeR) which predicts the glycan degradation potency of 10,000 reference glycans based on either genomic or metagenomic data. We first validated GlyDeR by comparing degradation profiles for genomes in the Human Microbiome Project against KEGG reaction annotations. Next, we applied GlyDeR to the analysis of human and mammalian gut microbial communities, which revealed that the glycan degradation potential of a community is strongly linked to host diet and can be used to predict diet with higher accuracy than sequence data alone. Finally, we show that a microbe's glycan degradation potential is significantly correlated (R = 0.46) with its abundance, with even higher correlations for potential pathogens such as the class Clostridia (R = 0.76). GlyDeR therefore represents an important tool for advancing our understanding of bacterial metabolism in the gut and for the future development of more effective prebiotics for microbial community manipulation. IMPORTANCE: The increased availability of high-throughput sequencing data has positioned the gut microbiota as a major new focal point for biomedical research. However, despite the expenditure of huge efforts and resources, sequencing-based analysis of the microbiome has uncovered mostly associative relationships between human health and diet, rather than a causal, mechanistic one. In order to utilize the full potential of systems biology approaches, one must first characterize the metabolic requirements of gut bacteria, specifically, the degradation of glycans, which are their primary nutritional source. We developed a computational framework called GlyDeR for integrating expert knowledge along with high throughput data to uncover important new relationships within glycan metabolism. GlyDeR analyzes particular bacterial (meta)genomes and predicts the potency by which they degrade a variety of different glycans. Based on GlyDeR, we found a clear connection between microbial glycan degradation and human diet, and we suggest a method for the rational design of novel prebiotics. PMID- 25118240 TI - Phyllosphere microbiota composition and microbial community transplantation on lettuce plants grown indoors. AB - The aerial surfaces of plants, or phyllosphere, are microbial habitats important to plant and human health. In order to accurately investigate microbial interactions in the phyllosphere under laboratory conditions, the composition of the phyllosphere microbiota should be representative of the diversity of microorganisms residing on plants in nature. We found that Romaine lettuce grown in the laboratory contained 10- to 100-fold lower numbers of bacteria than age matched, field-grown lettuce. The bacterial diversity on laboratory-grown plants was also significantly lower and contained relatively higher proportions of Betaproteobacteria as opposed to the Gammaproteobacteria-enriched communities on field lettuce. Incubation of field-grown Romaine lettuce plants in environmental growth chambers for 2 weeks resulted in bacterial cell densities and taxa similar to those on plants in the field but with less diverse bacterial populations overall. In comparison, the inoculation of laboratory-grown Romaine lettuce plants with either freshly collected or cryopreserved microorganisms recovered from field lettuce resulted in the development of a field-like microbiota on the lettuce within 2 days of application. The survival of an inoculated strain of Escherichia coli O157:H7 was unchanged by microbial community transfer; however, the inoculation of E. coli O157:H7 onto those plants resulted in significant shifts in the abundance of certain taxa. This finding was strictly dependent on the presence of a field-associated as opposed to a laboratory-associated microbiota on the plants. Phyllosphere microbiota transplantation in the laboratory will be useful for elucidating microbial interactions on plants that are important to agriculture and microbial food safety. IMPORTANCE: The phyllosphere is a habitat for a variety of microorganisms, including bacteria with significant relevance to plant and human health. Some indigenous epiphytic bacteria might affect the persistence of human food-borne pathogens in the phyllosphere. However, studies on human pathogens are typically performed on plants grown indoors. This study compares the phyllosphere microbiota on Romaine lettuce plants grown in a Salinas Valley, CA, field to that on lettuce plants grown in environmental chambers. We show that phyllosphere microbiota from laboratory-grown plants is distinct from that colonizing plants grown in the field and that the field microbiota can be successfully transferred to plants grown indoors. The microbiota transplantation method was used to examine alterations to the phyllosphere microbiota after Escherichia coli O157:H7 inoculation on lettuce plants in a controlled environment. Our findings show the importance and validity of phyllosphere microbiota transplantation for future phyllosphere microbiology research. PMID- 25118241 TI - Cross talk between the cell wall integrity and cyclic AMP/protein kinase A pathways in Cryptococcus neoformans. AB - Cryptococcus neoformans is a fungal pathogen of immunocompromised people that causes fatal meningitis. The fungal cell wall is essential to viability and pathogenesis of C. neoformans, and biosynthesis and repair of the wall is primarily controlled by the cell wall integrity (CWI) signaling pathway. Previous work has shown that deletion of genes encoding the four major kinases in the CWI signaling pathway, namely, PKC1, BCK1, MKK2, and MPK1 results in severe cell wall phenotypes, sensitivity to a variety of cell wall stressors, and for Mpk1, reduced virulence in a mouse model. Here, we examined the global transcriptional responses to gene deletions of BCK1, MKK2, and MPK1 compared to wild-type cells. We found that over 1,000 genes were differentially expressed in one or more of the deletion strains, with 115 genes differentially expressed in all three strains, many of which have been identified as genes regulated by the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. Biochemical measurements of cAMP levels in the kinase deletion strains revealed significantly less cAMP in all of the deletion strains compared to the wild-type strain. The deletion strains also produced significantly smaller capsules than the wild-type KN99 strain did under capsule-inducing conditions, although the levels of capsule they shed were similar to those shed by the wild type. Finally, addition of exogenous cAMP led to reduced sensitivity to cell wall stress and restored surface capsule to levels near those of wild type. Thus, we have direct evidence of cross talk between the CWI and cAMP/PKA pathways that may have important implications for regulation of cell wall and capsule homeostasis. IMPORTANCE: Cryptococcus neoformans is a fungal pathogen of immunocompromised people that causes fatal meningitis. The fungal cell wall is essential to viability and pathogenesis of C. neoformans, and biosynthesis and repair of the wall are primarily controlled by the cell wall integrity (CWI) signaling pathway. In this study, we demonstrate that deletion of any of three core kinases in the CWI pathway impacts not only the cell wall but also the amount of surface capsule. Deletion of any of the kinases results in significantly reduced cellular cyclic AMP (cAMP) levels, and addition of exogenous cAMP rescues the capsule defect and some cell wall defects, supporting a direct role for the CWI pathway in regulation of capsule in conjunction with the cAMP/protein kinase A pathway. PMID- 25118243 TI - Fur is the master regulator of the extraintestinal pathogenic Escherichia coli response to serum. AB - Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains are the major cause of colisepticemia (colibacillosis), a condition that has become an increasing public health problem in recent years. ExPEC strains are characterized by high resistance to serum, which is otherwise highly toxic to most bacteria. To understand how these bacteria survive and grow in serum, we performed system-wide analyses of their response to serum, making a clear distinction between the responses to nutritional immunity and innate immunity. Thus, mild heat inactivation of serum destroys the immune complement and abolishes the bactericidal effect of serum (inactive serum), making it possible to examine nutritional immunity. We used a combination of deep RNA sequencing and proteomics in order to characterize ExPEC genes whose expression is affected by the nutritional stress of serum and by the immune complement. The major change in gene expression induced by serum-active and inactive-involved metabolic genes. In particular, the serum metabolic response is coordinated by three transcriptional regulators, Fur, BasR, and CysB. Fur alone was responsible for more than 80% of the serum-induced transcriptional response. Consistent with its role as a major serum response regulator, deletion of Fur renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in colisepticemia and virulence. IMPORTANCE: Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains have emerged as major pathogens, especially in community- and hospital-acquired infections. These bacteria cause a large spectrum of syndromes, the most serious of which is septicemia, a condition with a high mortality rate. These bacterial strains are characterized by high resistance to serum, otherwise highly toxic to most bacteria. To understand the basis of this resistance, we carried out system-wide analyses of the response of ExPEC strains to serum by using proteomics and deep RNA sequencing. The major changes in gene expression induced by exposure to serum involved metabolic genes, not necessarily implicated in relation to virulence. One metabolic regulator-Fur involved in iron metabolism was responsible for more than 80% of the serum induced response, and its deletion renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in virulence. PMID- 25118244 TI - Pollen-specific activation of Arabidopsis retrogenes is associated with global transcriptional reprogramming. AB - Duplications allow for gene functional diversification and accelerate genome evolution. Occasionally, the transposon amplification machinery reverse transcribes the mRNA of a gene, integrates it into the genome, and forms an RNA duplicated copy: the retrogene. Although retrogenes have been found in plants, their biology and evolution are poorly understood. Here, we identified 251 (216 novel) retrogenes in Arabidopsis thaliana, corresponding to 1% of protein-coding genes. Arabidopsis retrogenes are derived from ubiquitously transcribed parents and reside in gene-rich chromosomal regions. Approximately 25% of retrogenes are cotranscribed with their parents and 3% with head-to-head oriented neighbors. This suggests transcription by novel promoters for 72% of Arabidopsis retrogenes. Many retrogenes reach their transcription maximum in pollen, the tissue analogous to animal spermatocytes, where upregulation of retrogenes has been found previously. This implies an evolutionarily conserved mechanism leading to this transcription pattern of RNA-duplicated genes. During transcriptional repression, retrogenes are depleted of permissive chromatin marks without an obvious enrichment for repressive modifications. However, this pattern is common to many other pollen-transcribed genes independent of their evolutionary origin. Hence, retroposition plays a role in plant genome evolution, and the developmental transcription pattern of retrogenes suggests an analogous regulation of RNA duplicated genes in plants and animals. PMID- 25118245 TI - Dynamics of vacuoles and H+-pyrophosphatase visualized by monomeric green fluorescent protein in Arabidopsis: artifactual bulbs and native intravacuolar spherical structures. AB - We prepared Arabidopsis thaliana lines expressing a functional green fluorescent protein (GFP)-linked vacuolar H(+)-pyrophosphatase (H(+)-PPase) under the control of its own promoter to investigate morphological dynamics of vacuoles and tissue specific expression of H(+)-PPase. The lines obtained had spherical structures in vacuoles with strong fluorescence, which are referred to as bulbs. Quantitative analyses revealed that the occurrence of the bulbs correlated with the amount of GFP. Next, we prepared a construct of H(+)-PPase linked with a nondimerizing GFP (mGFP); we detected no bulbs. These results indicate that the membranes adhere face-to-face by antiparallel dimerization of GFP, resulting in the formation of bulbs. In plants expressing H(+)-PPase-mGFP, intravacuolar spherical structures with double membranes, which differed from bulbs in fluorescence intensity and intermembrane spacing, were still observed in peripheral endosperm, pistil epidermis and hypocotyls. Four-dimensional imaging revealed the dynamics of formation, transformation, and disappearance of intravacuolar spherical structures and transvacuolar strands in living cells. Visualization of H(+)-PPase mGFP revealed intensive accumulation of the enzyme, not only in dividing and elongating cells but also in mesophyll, phloem, and nectary cells, which may have high sugar content. Dynamic morphological changes including transformation of vacuolar structures between transvacuolar strands, intravacuolar sheet-like structures, and intravacuolar spherical structures were also revealed. PMID- 25118248 TI - Advance consent, critical interests and dementia research. AB - Although advance directives have become a familiar instrument within the context of treatment, there has been minimal support for their expansion into the context of research. In this paper I argue that the principle of precedent autonomy that grants a competent person the right to refuse life-sustaining treatment when later incompetent, also grants a competent person the right to consent to research that is greater than minimal risk. An examination of the principle of precedent autonomy reveals that a future-binding research decision is within the scope of a competent person's critical interests, if the decision is consistent with what the person believes gives her life intrinsic value. PMID- 25118247 TI - Oligosaccharyltransferase subunits bind polypeptide substrate to locally enhance N-glycosylation. AB - Oligosaccharyltransferase is a multiprotein complex that catalyzes asparagine linked glycosylation of diverse proteins. Using yeast genetics and glycoproteomics, we found that transient interactions between nascent polypeptide and Ost3p/Ost6p, homologous subunits of oligosaccharyltransferase, were able to modulate glycosylation efficiency in a site-specific manner in vivo. These interactions were driven by hydrophobic and electrostatic complementarity between amino acids in the peptide-binding groove of Ost3p/Ost6p and the sequestered stretch of substrate polypeptide. Based on this dependence, we used in vivo scanning mutagenesis and in vitro biochemistry to map the precise interactions that affect site-specific glycosylation efficiency. We conclude that transient binding of substrate polypeptide by Ost3p/Ost6p increases glycosylation efficiency at asparagines proximal and C-terminal to sequestered sequences. We detail a novel mode of interaction between translocating nascent polypeptide and oligosaccharyltransferase in which binding to Ost3p/Ost6p segregates a short flexible loop of glycosylation-competent polypeptide substrate that is delivered to the oligosaccharyltransferase active site for efficient modification. PMID- 25118249 TI - Putative PmrA and PmcA are important for normal growth, morphogenesis and cell wall integrity, but not for viability in Aspergillus nidulans. AB - P-type Ca(2+)-transporting ATPases are Ca(2+) pumps, extruding cytosolic Ca(2+) to the extracellular environment or the intracellular Ca(2+) store lumens. In budding yeast, Pmr1 (plasma membrane ATPase related), and Pmc1 (plasma membrane calcium-ATPase) cannot be deleted simultaneously for it to survive in standard medium. Here, we deleted two putative Ca(2+) pumps, designated AnPmrA and AnPmcA, from Aspergillus nidulans, and obtained the mutants DeltaanpmrA and DeltaanpmcA, respectively. Then, using DeltaanpmrA as the starting strain, the promoter of its anpmcA was replaced with the alcA promoter to secure the mutant DeltaanpmrAalcApmcA or its anpmcA was deleted completely to produce the mutant DeltaanpmrADeltapmcA. Different from the case in Saccharomyces cerevisiae, double deletion of anpmrA and anpmcA was not lethal in A. nidulans. In addition, deletion of anpmrA and/or anpmcA had produced growth defects, although overexpression of AnPmc1 in DeltaanpmrAalcApmcA could not restore the growth defects that resulted from the loss of AnPmrA. Moreover, we found AnPmrA was indispensable for maintenance of normal morphogenesis, especially in low Ca(2+)/Mn(2+) environments. Thus, our findings suggest AnPmrA and AnPmcA might play important roles in growth, morphogenesis and cell wall integrity in A. nidulans in a different way from that in yeasts. PMID- 25118246 TI - Proteome-wide light/dark modulation of thiol oxidation in cyanobacteria revealed by quantitative site-specific redox proteomics. AB - Reversible protein thiol oxidation is an essential regulatory mechanism of photosynthesis, metabolism, and gene expression in photosynthetic organisms. Herein, we present proteome-wide quantitative and site-specific profiling of in vivo thiol oxidation modulated by light/dark in the cyanobacterium Synechocystis sp. PCC 6803, an oxygenic photosynthetic prokaryote, using a resin-assisted thiol enrichment approach. Our proteomic approach integrates resin-assisted enrichment with isobaric tandem mass tag labeling to enable site-specific and quantitative measurements of reversibly oxidized thiols. The redox dynamics of ~2,100 Cys sites from 1,060 proteins under light, dark, and 3-(3,4-dichlorophenyl)-1,1 dimethylurea (a photosystem II inhibitor) conditions were quantified. In addition to relative quantification, the stoichiometry or percentage of oxidation (reversibly oxidized/total thiols) for ~1,350 Cys-sites was also quantified. The overall results revealed broad changes in thiol oxidation in many key biological processes, including photosynthetic electron transport, carbon fixation, and glycolysis. Moreover, the redox sensitivity along with the stoichiometric data enabled prediction of potential functional Cys-sites for proteins of interest. The functional significance of redox-sensitive Cys-sites in NADP-dependent glyceraldehyde-3-phosphate dehydrogenase, peroxiredoxin (AhpC/TSA family protein Sll1621), and glucose 6-phosphate dehydrogenase was further confirmed with site specific mutagenesis and biochemical studies. Together, our findings provide significant insights into the broad redox regulation of photosynthetic organisms. PMID- 25118250 TI - Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio temporal distribution and function of membrane stress controller PspA in Escherichia coli. AB - All cell types must maintain the integrity of their membranes. The conserved bacterial membrane-associated protein PspA is a major effector acting upon extracytoplasmic stress and is implicated in protection of the inner membrane of pathogens, formation of biofilms and multi-drug-resistant persister cells. PspA and its homologues in Gram-positive bacteria and archaea protect the cell envelope whilst also supporting thylakoid biogenesis in cyanobacteria and higher plants. In enterobacteria, PspA is a dual function protein negatively regulating the Psp system in the absence of stress and acting as an effector of membrane integrity upon stress. We show that in Escherichia coli the low-order oligomeric PspA regulatory complex associates with cardiolipin-rich, curved polar inner membrane regions. There, cardiolipin and the flotillin 1 homologue YqiK support the PspBC sensors in transducing a membrane stress signal to the PspA-PspF inhibitory complex. After stress perception, PspA high-order oligomeric effector complexes initially assemble in polar membrane regions. Subsequently, the discrete spatial distribution and dynamics of PspA effector(s) in lateral membrane regions depend on the actin homologue MreB and the peptidoglycan machinery protein RodZ. The consequences of loss of cytoplasmic membrane anionic lipids, MreB, RodZ and/or YqiK suggest that the mode of action of the PspA effector is closely associated with cell envelope organization. PMID- 25118251 TI - Monophasic expression of FliC by Salmonella 4,[5],12:i:- DT193 does not alter its pathogenicity during infection of porcine intestinal epithelial cells. AB - Non-typhoidal serotypes of Salmonella enterica remain important food-borne pathogens worldwide and the frequent emergence of epidemic strains in food producing animals is a risk to public health. In recent years, Salmonella 4,[5],12:i:- isolates, expressing only phase 1 (FliC) of the two flagellar antigens, have emerged and increased in prevalence worldwide. In Europe, the majority of 4,[5],12:i:- isolates belong to phage types DT193 and DT120 of Salmonella Typhimurium and pigs have been identified as the reservoir species. In this study we investigated the ability of pig-derived monophasic (4,[5],12:i:-) and biphasic DT193 isolates to invade a porcine intestinal epithelial cell line (IPEC-1) and activate TLR-5, IL-8 and caspases. We found that the 4,[5],12:i:- isolates exhibited comparable adhesion and invasion to that of the virulent S. Typhimurium isolate 4/74, suggesting that these strains could be capable of colonizing the small intestine of pigs in vivo. Infection with 4,[5],12:i:- and biphasic DT193 isolates resulted in approximately the same level of TLR-5 (a flagellin receptor) and IL-8 (a proinflammatory chemokine) mRNA upregulation. The monophasic variants also elicited similar levels of caspase activation and cytotoxicity to the phase-variable DT193 isolates. These findings suggest that failure of 4,[5],12:i:- DT193 isolates to express a second phase of flagellar antigen (FljB) is unlikely to hamper their pathogenicity during colonization of the porcine intestinal tract. PMID- 25118252 TI - Evolution of a genome-encoded bias in amino acid biosynthetic pathways is a potential indicator of amino acid dynamics in the environment. AB - Overcoming the stress of starvation is one of an organism's most challenging phenotypic responses. Those organisms that frequently survive the challenge, by virtue of their fitness, will have evolved genomes that are shaped by their specific environments. Understanding this genotype-environment-phenotype relationship at a deep level will require quantitative predictive models of the complex molecular systems that link these aspects of an organism's existence. Here, we treat one of the most fundamental molecular systems, protein synthesis, and the amino acid biosynthetic pathways involved in the stringent response to starvation. These systems face an inherent logical dilemma: Building an amino acid biosynthetic pathway to synthesize its product-the cognate amino acid of the pathway-may require that very amino acid when it is no longer available. To study this potential "catch-22," we have created a generic model of amino acid biosynthesis in response to sudden starvation. Our mathematical analysis and computational results indicate that there are two distinctly different outcomes: Partial recovery to a new steady state, or full system failure. Moreover, the cell's fate is dictated by the cognate bias, the number of cognate amino acids in the corresponding biosynthetic pathway relative to the average number of that amino acid in the proteome. We test these implications by analyzing the proteomes of over 1,800 sequenced microbes, which reveals statistically significant evidence of low cognate bias, a genetic trait that would avoid the biosynthetic quandary. Furthermore, these results suggest that the pattern of cognate bias, which is readily derived by genome sequencing, may provide evolutionary clues to an organism's natural environment. PMID- 25118254 TI - Root-secreted nicotianamine from Arabidopsis halleri facilitates zinc hypertolerance by regulating zinc bioavailability. AB - Hyperaccumulators tolerate and accumulate extraordinarily high concentrations of heavy metals. Content of the metal chelator nicotianamine (NA) in the root of zinc hyperaccumulator Arabidopsis halleri is elevated compared with nonhyperaccumulators, a trait that is considered to be one of the markers of a hyperaccumulator. Using metabolite-profiling analysis of root secretions, we found that excess zinc treatment induced secretion of NA in A. halleri roots compared with the nonhyperaccumulator Arabidopsis thaliana. Metal speciation analysis further revealed that the secreted NA forms a stable complex with Zn(II). Supplying NA to a nonhyperaccumulator species markedly increased plant zinc tolerance by decreasing zinc uptake. Therefore, NA secretion from A. halleri roots facilitates zinc hypertolerance through forming a Zn(II)-NA complex outside the roots to achieve a coordinated zinc uptake rate into roots. Secretion of NA was also found to be responsible for the maintenance of iron homeostasis under excess zinc. Together our results reveal root-secretion mechanisms associated with hypertolerance and hyperaccumulation. PMID- 25118256 TI - Digital inventory of Arabidopsis transcripts revealed by 61 RNA sequencing samples. AB - Alternative splicing is an essential biological process to generate proteome diversity and phenotypic complexity. Recent improvements in RNA sequencing accuracy and computational algorithms have provided unprecedented opportunities to examine the expression levels of Arabidopsis (Arabidopsis thaliana) transcripts. In this article, we analyzed 61 RNA sequencing samples from 10 totally independent studies of Arabidopsis and calculated the transcript expression levels in different tissues, treatments, developmental stages, and varieties. These data provide a comprehensive profile of Arabidopsis transcripts with single-base resolution. We quantified the expression levels of 40,745 transcripts annotated in The Arabidopsis Information Resource 10, comprising 73% common transcripts, 15% rare transcripts, and 12% nondetectable transcripts. In addition, we investigated diverse common transcripts in detail, including ubiquitous transcripts, dominant/subordinate transcripts, and switch transcripts, in terms of their expression and transcript ratio. Interestingly, alternative splicing was the highly enriched function for the genes related to dominant/subordinate transcripts and switch transcripts. In addition, motif analysis revealed that TC motifs were enriched in dominant transcripts but not in subordinate transcripts. These motifs were found to have a strong relationship with transcription factor activity. Our results shed light on the complexity of alternative splicing and the diversity of the contributing factors. PMID- 25118259 TI - RESTORE: REcovery after Serious Trauma--Outcomes, Resource use and patient Experiences study protocol. AB - BACKGROUND: Traumatic injury is a leading contributor to the overall global burden of disease. However, there is a worldwide shortage of population data to inform understanding of non-fatal injury burden. An improved understanding of the pattern of recovery following trauma is needed to better estimate the burden of injury, guide provision of rehabilitation services and care to injured people, and inform guidelines for the monitoring and evaluation of disability outcomes. OBJECTIVE: To provide a comprehensive overview of patient outcomes and experiences in the first 5 years after serious injury. DESIGN: This is a population-based, nested prospective cohort study using quantitative data methods, supplemented by a qualitative study of a seriously injured participant sample. PARTICIPANTS: All 2547 paediatric and adult major trauma patients captured by the Victorian State Trauma Registry with a date of injury from 1 July 2011 to 30 June 2012 who survived to hospital discharge and did not opt-off from the registry. ANALYSIS: To analyse the quantitative data and identify factors that predict poor or good outcome, whether there is change over time, differences in rates of recovery and change between key participant subgroups, multilevel mixed effects regression models will be fitted. To analyse the qualitative data, thematic analysis will be used to identify important themes and the relationships between themes. CONTRIBUTION TO THE FIELD: The results of this project have the potential to inform clinical decisions and public health policy, which can reduce the burden of non-fatal injury and improve the lives of people living with the consequences of severe injury. PMID- 25118260 TI - TAK1 inhibition accelerates cellular senescence of retinal pigment epithelial cells. AB - PURPOSE: Oxidative stress and cellular senescence are known to contribute to the development of AMD; however, the mechanism is not fully understood. This study investigated the role of TGF-beta-activated kinase 1 (TAK1) in the senescence of RPE cells as a model for the development of dry AMD. METHODS: Cultured human RPE cells were treated with the TAK1 inhibitor 5Z-7-oxozeaenol for 1 hour, and then treated with 200 MUM hydrogen peroxide for 1 hour. Human RPE cells that were not pretreated with TAK1 inhibitor for 1 hour served as controls. Senescence associated beta-galactosidase (SA-beta-gal) activity was detected by histochemistry, and p53 expression by immunoblotting. Cell-cycle and apoptosis rate in RPE cells were determined by flow cytometry. RESULTS: The TAK1 expression in human RPE cells was high and was altered on oxidative stress. Transforming growth factor-beta-activated kinase 1 inhibition led to reduction in cell proliferation, cell-cycle arrest at G0/G1, and increased SA-beta-gal expression, all known to be features of cell senescence. Exposure of cells to oxidative stress combined with inhibition of TAK1 activity decreased the expression of apoptotic proteins, such as p53, and promoted cellular senescence. Aberrant TAK1 activity in RPE cells triggered their secretion of factors that induced hypertrophy and fibrotic changes in neighboring cells. CONCLUSIONS: The in vitro evidence indicated a role for TAK1 in the onset of senescence in RPE cells. The data shown hereby demonstrated that TAK1 activity is essential for maintaining normal function of RPE cells. Elucidation of its role in mechanisms underlying RPE cellular senescence induction may potentiate development of powerful tools for halting the development of dry AMD. PMID- 25118253 TI - Biotic interactions in the rhizosphere: a diverse cooperative enterprise for plant productivity. AB - Microbes and plants have evolved biochemical mechanisms to communicate with each other. The molecules responsible for such communication are secreted during beneficial or harmful interactions. Hundreds of these molecules secreted into the rhizosphere have been identified, and their functions are being studied in order to understand the mechanisms of interaction and communication among the different members of the rhizosphere community. The importance of root and microbe secretion to the underground habitat in improving crop productivity is increasingly recognized, with the discovery and characterization of new secreting compounds found in the rhizosphere. Different omic approaches, such as genomics, transcriptomics, proteomics, and metabolomics, have expanded our understanding of the first signals between microbes and plants. In this review, we highlight the more recent discoveries related to molecules secreted into the rhizosphere and how they affect plant productivity, either negatively or positively. In addition, we include a survey of novel approaches to studying the rhizosphere and emerging opportunities to direct future studies. PMID- 25118255 TI - Large-scale identification of gibberellin-related transcription factors defines group VII ETHYLENE RESPONSE FACTORS as functional DELLA partners. AB - DELLA proteins are the master negative regulators in gibberellin (GA) signaling acting in the nucleus as transcriptional regulators. The current view of DELLA action indicates that their activity relies on the physical interaction with transcription factors (TFs). Therefore, the identification of TFs through which DELLAs regulate GA responses is key to understanding these responses from a mechanistic point of view. Here, we have determined the TF interactome of the Arabidopsis (Arabidopsis thaliana) DELLA protein GIBBERELLIN INSENSITIVE and screened a collection of conditional TF overexpressors in search of those that alter GA sensitivity. As a result, we have found RELATED TO APETALA2.3, an ethylene-induced TF belonging to the group VII ETHYLENE RESPONSE FACTOR of the APETALA2/ethylene responsive element binding protein superfamily, as a DELLA interactor with physiological relevance in the context of apical hook development. The combination of transactivation assays and chromatin immunoprecipitation indicates that the interaction with GIBBERELLIN INSENSITIVE impairs the activity of RELATED TO APETALA2.3 on the target promoters. This mechanism represents a unique node in the cross regulation between the GA and ethylene signaling pathways controlling differential growth during apical hook development. PMID- 25118261 TI - Increased corneal epithelial permeability after overnight sleep. AB - PURPOSE: To investigate factors of ethnicity, sex, age, and diurnal variation on human corneal epithelial permeability. METHODS: Data of corneal epithelial permeability to sodium fluorescein (Pdc) were collected from 374 noncontact lens wearers at various times after awakening throughout the day. Mixed-effect models were developed to investigate the association between Pdc and factors of interest, including time awake (TA), age, sex, ethnicity, and interactions of these factors. RESULTS: Two models evaluated the "Pdc recovery period" from awakening to 2 hours (Model 1) and the "Pdc plateau" period after TA of 2 hours (Model 2). In Model 1, Pdc declined significantly with length of awake time (P = 0.000), and showed higher Pdc with males (P = 0.098), although this sex difference was not observed after 2 hours (Model 2). Both models showed significantly higher Pdc in Asians than in non-Asians (P = 0.000) and increased Pdc with age (P = 0.048, P = 0.001). CONCLUSIONS: Baseline corneal epithelial barrier function increases after overnight sleep and varies significantly by ethnicity and age. PMID- 25118262 TI - Posterior pole asymmetry analyses of retinal thickness of upper and lower sectors and their association with peak retinal nerve fiber layer thickness in healthy young eyes. AB - PURPOSE: To determine the symmetry of the retinal thicknesses (RT) between the 32 pairs of superior and inferior sectors by posterior pole asymmetrical analysis (PPAA) of the spectral-domain optical coherence tomographic (SD-OCT) images in healthy eyes. In addition, to determine their association with the position of the peak retinal nerve fiber layer (RNFL) thickness. METHODS: A prospective, observational, cross-sectional study of 64 right eyes. The Spectralis SD-OCT was used to obtain the images, and the PPAA determined the RT of the 64 cells within the central 24 degrees area. The program also compared the thicknesses of corresponding cells across the fovea-disc axis. Circular scans were used to measure the supra- and infratemporal RNFL peak angle differences (PADs). The relationships between the RT of the corresponding cells and the relationship between the differences of the RT of the corresponding cells and PAD were investigated by linear regression analysis. RESULTS: The mean differences between the RT of corresponding cells ranged from 3.1 to 23.2 MUm. The RT of all upper cells were significantly correlated with the RT of the corresponding lower cells (R = 0.45-0.97, P < 0.001). The coefficients of correlation between the corresponding pairs of central- and temporal-macular cells were higher than that of the peripheral and nasal-macular cells. The differences of the pairs of nasal macular cells RT were significantly correlated with the PAD. CONCLUSIONS: The symmetry of the RT between the upper and lower cells was high in the central and temporal-macular areas but not in the peripheral and nasal-macular areas. (www.umin.ac.jp/ctr number, UMIN000006040.). PMID- 25118263 TI - Quantitative analysis of functional changes caused by pinhole glasses. AB - PURPOSE: To quantify the visual functional changes caused by pinhole glasses. METHODS: Healthy subjects underwent ophthalmic examinations including uncorrected distance visual acuity (UDVA) and corrected near visual acuity (CNVA), pupil size, depth of focus (DOF), accommodative amplitude, visual field (VF) test, contrast sensitivity (CS), and stereopsis. Subjects underwent the same examinations while wearing pinhole glasses 1 week later. RESULTS: Forty-eight eyes of 48 subjects (24 male and 24 female) with a mean age of 35.5+/-6.7 years and a mean spherical equivalent of -2.4+/-3.3 diopters (D) were enrolled. The pinhole glasses significantly improved UDVA and CNVA (logMAR) from 0.44+/-0.46 and 0.26+/-0.40 to 0.19+/-0.25 and 0.14+/-0.22, respectively. The pinhole glasses markedly enlarged pupils from 3.6+/-0.5 mm photopic size to 6.0+/-0.5 mm, very close to the mesopic size of 6.2+/-0.6 mm. Mean DOF and accommodative amplitude also significantly increased by approximately 50%, while VF featured a general reduction of sensitivity. Mean deviation (MD) significantly decreased from 0.48+/-1.57 to -4.22+/-1.66 dB, and visual field index (VFI) decreased from 99.4+/-0.7% to 98.4+/-1.3%. The CS decreased significantly at all four spatial frequencies, and stereopsis deteriorated with pinhole glasses. CONCLUSIONS: The pinhole glasses improved visual acuity, DOF, and accommodative amplitude; however, they resulted in decreased visual quality including general reduction of VF sensitivity, CS, and stereopsis. Therefore, particular attention is needed when wearing pinhole glasses while driving, playing sports, or working with instruments. (ClinicalTrials.gov number, NCT02111356.). PMID- 25118264 TI - Generation and characterization of a murine model of Bietti crystalline dystrophy. AB - PURPOSE: Bietti crystalline dystrophy (BCD) is a rare, autosomal recessive, progressive, degenerative eye disease caused by mutations in the CYP4V2 gene, for which no treatments are currently available. Cyp4v3 is the murine ortholog to CYP4V2, and to better understand the molecular pathogenesis of this disease we have established a Cyp4v3-null mouse line. METHODS: Cyp4v3(-/-) mice were generated by homologous recombination in embryonic stem cells. Ocular morphologic characteristics were evaluated via fundus imaging, plasma lipid profiling, and histologic analysis via Oil Red O reactivity, hematoxylin and eosin staining, and transmission electron microscopy. RESULTS: The Cyp4v3(-/-) mouse recapitulates the characteristic features of corneoretinal crystal accumulation and systemic dyslipidemia seen in BCD. The Cyp4v3(-/-) mice behave normally and are viable and fertile when maintained under specific pathogen-free (SPF) housing conditions. CONCLUSIONS: Cyp4v3(-/-) mice represent a promising preclinical model that may be used to better understand the disease etiology and to evaluate pharmacotherapies for this devastating condition. PMID- 25118266 TI - Schlemm's canal expands after trabeculectomy in patients with primary angle closure glaucoma. AB - PURPOSE: To evaluate the in vivo changes in the Schlemm's canal (SC) in patients with primary angle-closure glaucoma (PACG) after trabeculectomy using spectral domain optical coherence tomography (SD-OCT). METHODS: Forty eyes of 40 patients with PACG who underwent trabeculectomy were included. All participants underwent SD-OCT. The diameter and area of SC were examined and measured before and within 1 month after trabeculectomy. All SD-OCT images were processed using adaptive compensation algorithm to improve contrast and image quality. Multivariate linear regression analysis was performed for predictors of percentage change in the mean SC diameter and area. RESULTS: The mean age of participants was 60.5 +/- 14.6 years. Adaptive compensation significantly increased the percentage of sections in which SC was observable in the subjects studied from 52.5% (21/40) to 75.0% (30/40), which has acceptable intraobserver and interobserver repeatability. There was a significant increase in the SC diameter and area at the follow-up examination compared with the baseline value (SC diameter: 34.2 +/- 6.2 MUm vs. 28.4 +/- 6.1 MUm; SC area: 8117 +/- 1942 MUm(2) vs. 5200 +/- 996 MUm(2); all P < 0.001). After multivariate analysis, the only variable related to changes in SC was percentage change in IOP (SC diameter, P = 0.002; SC area, P < 0.001). In addition, the magnitude of the change in the SC area also correlated with angle opening distance at 750 MUm from the scleral spur at baseline. CONCLUSIONS: Expansion of SC was observed after trabeculectomy in PACG patients. The degree of SC expansion was related to the extent of the IOP decrease. PMID- 25118267 TI - A topographical relationship between visual field defects and optic radiation changes in glaucoma. AB - PURPOSE: To investigate the topographic relationship between glaucomatous retinal ganglion cell loss and changes in the optic radiation (OR) using diffusion tensor imaging (DTI). METHODS: A cross-sectional study was completed on nine patients with primary open angle glaucoma and nine age- and sex-matched controls. Glaucoma patients with binocular, symmetrical superior, or inferior visual hemifield defects were selected. A comparative DTI analysis was conducted between OR fibers connected to the affected and unaffected visual hemifield in the glaucoma group and corresponding OR in the control group. RESULTS: There was a significantly lower number of fiber bundles in the affected OR compared with unaffected OR and controls (P < 0.01). Radial diffusivity was similar between the affected and unaffected OR (P = 0.39), but higher in both groups compared with controls (P < 0.01). There was no difference in axial diffusivity among all groups. As a consequence, fractional anisotropy was lower and mean diffusivity was higher in the affected and unaffected OR compared with controls. CONCLUSIONS: A significant loss of OR fibers connected to the severely damaged part of the optic nerve head, but not the fibers connected to the relatively spared retinal hemifield shows a direct relationship between retinal neuronal damage and functionally connected OR fibers in glaucoma. However, OR fibers connected to the relatively preserved visual hemifield in the glaucoma subjects still showed changes in radial diffusivity compared with controls, suggesting possible early dysfunction. Our results support the notion that glaucoma is a neurodegenerative disease involving the posterior visual pathway. PMID- 25118265 TI - Loss of outer retinal neurons and circuitry alterations in the DBA/2J mouse. AB - PURPOSE: The DBA/2J mouse line develops essential iris atrophy, pigment dispersion, and glaucomatous age-related changes, including an increase of IOP, optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study was to evaluate possible morphological changes in the outer retina of the DBA/2J mouse concomitant with disease progression and aging, based on the reduction of both the a- and b-waves and photopic flicker ERGs in this mouse line. METHODS: Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old C57BL/6 mice retinas were used as controls. RESULTS: The DBA/2J mice had outer retinal degeneration at all ages, with the most severe degeneration in the oldest retinas. At 3 months of age, the number of photoreceptor cells and the thickness of the OPL were reduced. In addition, there was a loss of horizontal and ON bipolar cell processes. At 8 months of age, RGC degeneration occurred in patches, and in the outer retina overlying these patches, cone morphology was impaired with a reduction in size as well as loss of outer segments and growth of horizontal and bipolar cell processes into the outer nuclear layer. At 16 months of age, connectivity between photoreceptors and horizontal and bipolar cell processes overlying these patches was lost. CONCLUSIONS: Retinal degeneration in DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell processes, and loss of synaptic contacts in an aging-dependent manner. PMID- 25118268 TI - Mitochondrial haplogroups are associated with severity of diabetic retinopathy. AB - PURPOSE: To determine if specific mitochondrial haplogroups associate with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). METHODS: Deidentified medical records for Caucasian patients with diabetic retinopathy (DR; 153 NPDR and 138 PDR) were obtained from BioVU, Vanderbilt University's electronic, deidentified DNA databank. An independent cohort of Caucasian patients with DR (44 NPDR and 57 PDR) from the Vanderbilt Eye Institute (VEI) was used for validation. We tested for an association between mitochondrial haplogroups and PDR among patients with DR. RESULTS: In the BioVU cohort, PDR frequency among Caucasian DR patients differed significantly by mitochondrial haplogroup (P = 0.027). Replication in the VEI cohort confirmed this association (P = 0.0064). In the combined cohort, patients from the common haplogroup H were more likely to have PDR (odds ratio [OR] = 2.0 [95% confidence interval (CI) = 1.3-3.0], P = 0.0012), while patients from haplogroup Uk were less likely to have PDR (OR = 0.5 [95% CI = 0.3-0.8], P = 0.0049). In logistic regression analyses, the addition of diabetes duration, hemoglobin A1c (HgbA1c) levels, and hypertension had no effect on the associations of haplogroups H and Uk with PDR. CONCLUSIONS: In this study, DR patients from mitochondrial haplogroup H were more likely to have PDR, while DR patients from haplogroup Uk were less likely to have PDR. The association was independent of the major clinical variables affecting PDR. The mitochondrial haplogroups were as strong a risk factor for PDR as were elevated HgbA1c levels. PMID- 25118271 TI - Glycopeptide use is associated with increased mortality in Enterococcus faecalis bacteraemia--authors' response. PMID- 25118272 TI - Science and culture: dangerous doilies. Interview by Rebecca Horne. PMID- 25118270 TI - Homogeneity of antimicrobial policy, yet heterogeneity of antimicrobial resistance: antimicrobial non-susceptibility among 108,717 clinical isolates from primary, secondary and tertiary care patients in London. AB - OBJECTIVES: We examined the 4 year trend in antimicrobial susceptibilities and prescribing across levels of care at two London teaching hospitals and their multisite renal unit, and for the surrounding community. METHODS: Laboratory and pharmacy information management systems were interrogated, with antimicrobial use and susceptibilities analysed between hospitals, within hospitals and over time. RESULTS: A total of 108,717 isolates from 71,687 patients were identified, with significant differences (at P < 0.05) in antimicrobial susceptibility between and within hospitals. Across the 4 years, rates of ESBL-/AmpC-producing Enterobacteriaceae ranged from 6.4% to 10.7% among community isolates, 17.8% to 26.9% at ward level and 25.2% to 52.5% in critical care. Significant variations were also demonstrated in glycopeptide-resistant enterococci (ward level 6.2% 17.4%; critical care 21.9%-56.3%), MRSA (ward level 18.5%-38.2%; critical care 12.5%-47.9%) and carbapenem-resistant Pseudomonas spp. (ward level 8.3%-16.9%; critical care 19.9%-53.7%). Few instances of persistently higher resistance were seen between the hospitals in equivalent cohorts, despite persistently higher antimicrobial use in Hospital 1 than Hospital 2. We found significant fluctuations in non-susceptibility year on year across the cohorts, but with few persistent trends. CONCLUSIONS: The marked heterogeneity of antimicrobial susceptibilities between hospitals, within hospitals and over time demands detailed, standardized surveillance and appropriate benchmarking to identify possible drivers and effective interventions. Homogeneous antimicrobial policies are unlikely to continue to be suitable as individual hospitals join hospital networks, and policies should be tailored to local resistance rates, at least at the hospital level, and possibly with finer resolution, particularly for critical care. PMID- 25118274 TI - Fungal polyketide engineering comes of age. PMID- 25118275 TI - PIP5K1alpha inhibition as a therapeutic strategy for prostate cancer. PMID- 25118269 TI - Genetic variants associated with severe retinopathy of prematurity in extremely low birth weight infants. AB - PURPOSE: To determine genetic variants associated with severe retinopathy of prematurity (ROP) in a candidate gene cohort study of US preterm infants. METHODS: Preterm infants in the discovery cohort were enrolled through the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, and those in the replication cohort were from the University of Iowa. All infants were phenotyped for ROP severity. Because of differences in the durations of enrollment between cohorts, severe ROP was defined as threshold disease in the discovery cohort and as threshold disease or type 1 ROP in the replication cohort. Whole genome amplified DNA from stored blood spot samples from the Neonatal Research Network biorepository was genotyped using an Illumina GoldenGate platform for candidate gene single nucleotide polymorphisms (SNPs) involving angiogenic, developmental, inflammatory, and oxidative pathways. Three analyses were performed to determine significant epidemiologic variables and SNPs associated with levels of ROP severity. Analyses controlled for multiple comparisons, ancestral eigenvalues, family relatedness, and significant epidemiologic variables. Single nucleotide polymorphisms significantly associated with ROP severity from the discovery cohort were analyzed in the replication cohort and in meta-analysis. RESULTS: Eight hundred seventeen infants in the discovery cohort and 543 in the replication cohort were analyzed. Severe ROP occurred in 126 infants in the discovery and in 14 in the replication cohort. In both cohorts, ventilation days and seizure occurrence were associated with severe ROP. After controlling for significant factors and multiple comparisons, two intronic SNPs in the gene BDNF (rs7934165 and rs2049046, P < 3.1 * 10(-5)) were associated with severe ROP in the discovery cohort and were not associated with severe ROP in the replication cohort. However, when the cohorts were analyzed together in an exploratory meta-analysis, rs7934165 increased in associated significance with severe ROP (P = 2.9 * 10(-7)). CONCLUSIONS: Variants in BDNF encoding brain-derived neurotrophic factor were associated with severe ROP in a large candidate gene study of infants with threshold ROP. PMID- 25118279 TI - Imaging of the cerebello-pontine angle. PMID- 25118276 TI - KLRG+ invariant natural killer T cells are long-lived effectors. AB - Immunological memory has been regarded as a unique feature of the adaptive immune response mediated in an antigen-specific manner by T and B lymphocytes. However, natural killer (NK) cells and gammadeltaT cells, which traditionally are classified as innate immune cells, have been shown in recent studies to have hallmark features of memory cells. Invariant NKT cell (iNKT cell)-mediated antitumor effects indicate that iNKT cells are activated in vivo by vaccination with iNKT cell ligand-loaded CD1d(+) cells, but not by vaccination with unbound NKT cell ligand. In such models, it previously was thought that the numbers of IFN-gamma-producing cells in the spleen returned to the basal level around 1 wk after the vaccination. In the current study, we demonstrate the surprising presence of effector memory-like iNKT cells in the lung. We found long-term antitumor activity in the lungs of mice was enhanced after vaccination with iNKT cell ligand-loaded dendritic cells. Further analyses showed that the KLRG1(+) (Killer cell lectin-like receptor subfamily G, member 1-positive) iNKT cells coexpressing CD49d and granzyme A persisted for several months and displayed a potent secondary response to cognate antigen. Finally, analyses of CDR3beta by RNA deep sequencing demonstrated that some particular KLRG1(+) iNKT-cell clones accumulated, suggesting the selection of certain T-cell receptor repertoires by an antigen. The current findings identifying effector memory-like KLRG1(+) iNKT cells in the lung could result in a paradigm shift regarding the basis of newly developed extrathymic iNKT cells and could contribute to the future development of antitumor immunotherapy by uniquely energizing iNKT cells. PMID- 25118278 TI - Engineered kinase activation reveals unique morphodynamic phenotypes and associated trafficking for Src family isoforms. AB - The Src kinase family comprises nine homologous members whose distinct expression patterns and cellular distributions indicate that they have unique roles. These roles have not been determined because genetic manipulation has not produced clearly distinct phenotypes, and the kinases' homology complicates generation of specific inhibitors. Through insertion of a modified FK506 binding protein (insertable FKBP12, iFKBP) into the protein kinase isoforms Fyn, Src, Lyn, and Yes, we engineered kinase analogs that can be activated within minutes in living cells (RapR analogs). Combining our RapR analogs with computational tools for quantifying and characterizing cellular dynamics, we demonstrate that Src family isoforms produce very different phenotypes, encompassing cell spreading, polarized motility, and production of long, thin cell extensions. Activation of Src and Fyn led to patterns of kinase translocation that correlated with morphological changes in temporally distinct stages. Phenotypes were dependent on N-terminal acylation, not on Src homology 3 (SH3) and Src homology 2 (SH2) domains, and correlated with movement between a perinuclear compartment, adhesions, and the plasma membrane. PMID- 25118277 TI - Immature truncated O-glycophenotype of cancer directly induces oncogenic features. AB - Aberrant expression of immature truncated O-glycans is a characteristic feature observed on virtually all epithelial cancer cells, and a very high frequency is observed in early epithelial premalignant lesions that precede the development of adenocarcinomas. Expression of the truncated O-glycan structures Tn and sialyl-Tn is strongly associated with poor prognosis and overall low survival. The genetic and biosynthetic mechanisms leading to accumulation of truncated O-glycans are not fully understood and include mutation or dysregulation of glycosyltransferases involved in elongation of O-glycans, as well as relocation of glycosyltransferases controlling initiation of O-glycosylation from Golgi to endoplasmic reticulum. Truncated O-glycans have been proposed to play functional roles for cancer-cell invasiveness, but our understanding of the biological functions of aberrant glycosylation in cancer is still highly limited. Here, we used exome sequencing of most glycosyltransferases in a large series of primary and metastatic pancreatic cancers to rule out somatic mutations as a cause of expression of truncated O-glycans. Instead, we found hypermethylation of core 1 beta3-Gal-T-specific molecular chaperone, a key chaperone for O-glycan elongation, as the most prevalent cause. We next used gene editing to produce isogenic cell systems with and without homogenous truncated O-glycans that enabled, to our knowledge, the first polyomic and side-by-side evaluation of the cancer O-glycophenotype in an organotypic tissue model and in xenografts. The results strongly suggest that truncation of O-glycans directly induces oncogenic features of cell growth and invasion. The study provides support for targeting cancer-specific truncated O-glycans with immunotherapeutic measures. PMID- 25118280 TI - Interaction of HIV-1 Nef protein with the host protein Alix promotes lysosomal targeting of CD4 receptor. AB - Nef is an accessory protein of human immunodeficiency viruses that promotes viral replication and progression to AIDS through interference with various host trafficking and signaling pathways. A key function of Nef is the down-regulation of the coreceptor CD4 from the surface of the host cells. Nef-induced CD4 down regulation involves at least two independent steps as follows: acceleration of CD4 endocytosis by a clathrin/AP-2-dependent pathway and targeting of internalized CD4 to multivesicular bodies (MVBs) for eventual degradation in lysosomes. In a previous work, we found that CD4 targeting to the MVB pathway was independent of CD4 ubiquitination. Here, we report that this targeting depends on a direct interaction of Nef with Alix/AIP1, a protein associated with the endosomal sorting complexes required for transport (ESCRT) machinery that assists with cargo recruitment and intraluminal vesicle formation in MVBs. We show that Nef interacts with both the Bro1 and V domains of Alix. Depletion of Alix or overexpression of the Alix V domain impairs lysosomal degradation of CD4 induced by Nef. In contrast, the V domain overexpression does not prevent cell surface removal of CD4 by Nef or protein targeting to the canonical ubiquitination dependent MVB pathway. We also show that the Nef-Alix interaction occurs in late endosomes that are enriched in internalized CD4. Together, our results indicate that Alix functions as an adaptor for the ESCRT-dependent, ubiquitin-independent targeting of CD4 to the MVB pathway induced by Nef. PMID- 25118281 TI - The T4 phage DNA mimic protein Arn inhibits the DNA binding activity of the bacterial histone-like protein H-NS. AB - The T4 phage protein Arn (Anti restriction nuclease) was identified as an inhibitor of the restriction enzyme McrBC. However, until now its molecular mechanism remained unclear. In the present study we used structural approaches to investigate biological properties of Arn. A structural analysis of Arn revealed that its shape and negative charge distribution are similar to dsDNA, suggesting that this protein could act as a DNA mimic. In a subsequent proteomic analysis, we found that the bacterial histone-like protein H-NS interacts with Arn, implying a new function. An electrophoretic mobility shift assay showed that Arn prevents H-NS from binding to the Escherichia coli hns and T4 p8.1 promoters. In vitro gene expression and electron microscopy analyses also indicated that Arn counteracts the gene-silencing effect of H-NS on a reporter gene. Because McrBC and H-NS both participate in the host defense system, our findings suggest that T4 Arn might knock down these mechanisms using its DNA mimicking properties. PMID- 25118282 TI - Cathepsin S causes inflammatory pain via biased agonism of PAR2 and TRPV4. AB - Serine proteases such as trypsin and mast cell tryptase cleave protease-activated receptor-2 (PAR2) at R(36)?S(37) and reveal a tethered ligand that excites nociceptors, causing neurogenic inflammation and pain. Whether proteases that cleave PAR2 at distinct sites are biased agonists that also induce inflammation and pain is unexplored. Cathepsin S (Cat-S) is a lysosomal cysteine protease of antigen-presenting cells that is secreted during inflammation and which retains activity at extracellular pH. We observed that Cat-S cleaved PAR2 at E(56)?T(57), which removed the canonical tethered ligand and prevented trypsin activation. In HEK and KNRK cell lines and in nociceptive neurons of mouse dorsal root ganglia, Cat-S and a decapeptide mimicking the Cat-S-revealed tethered ligand-stimulated PAR2 coupling to Galphas and formation of cAMP. In contrast to trypsin, Cat-S did not mobilize intracellular Ca(2+), activate ERK1/2, recruit beta-arrestins, or induce PAR2 endocytosis. Cat-S caused PAR2-dependent activation of transient receptor potential vanilloid 4 (TRPV4) in Xenopus laevis oocytes, HEK cells and nociceptive neurons, and stimulated neuronal hyperexcitability by adenylyl cyclase and protein kinase A-dependent mechanisms. Intraplantar injection of Cat S caused inflammation and hyperalgesia in mice that was attenuated by PAR2 or TRPV4 deletion and adenylyl cyclase inhibition. Cat-S and PAR2 antagonists suppressed formalin-induced inflammation and pain, which implicates endogenous Cat-S and PAR2 in inflammatory pain. Our results identify Cat-S as a biased agonist of PAR2 that causes PAR2- and TRPV4-dependent inflammation and pain. They expand the role of PAR2 as a mediator of protease-driven inflammatory pain. PMID- 25118283 TI - A critical role of the C-terminal segment for allosteric inhibitor-induced aberrant multimerization of HIV-1 integrase. AB - Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are a promising class of antiretroviral agents for clinical development. Although ALLINIs promote aberrant IN multimerization and inhibit IN interaction with its cellular cofactor LEDGF/p75 with comparable potencies in vitro, their primary mechanism of action in infected cells is through inducing aberrant multimerization of IN. Crystal structures have shown that ALLINIs bind at the IN catalytic core domain dimer interface and bridge two interacting subunits. However, how these interactions promote higher-order protein multimerization is not clear. Here, we used mass spectrometry-based protein footprinting to monitor surface topology changes in full-length WT and the drug-resistant A128T mutant INs in the presence of ALLINI 2. These experiments have identified protein-protein interactions that extend beyond the direct inhibitor binding site and which lead to aberrant multimerization of WT but not A128T IN. Specifically, we demonstrate that C terminal residues Lys-264 and Lys-266 play an important role in the inhibitor induced aberrant multimerization of the WT protein. Our findings provide structural clues for exploiting IN multimerization as a new, attractive therapeutic target and are expected to facilitate development of improved inhibitors. PMID- 25118284 TI - Amyloid-beta peptide-specific DARPins as a novel class of potential therapeutics for Alzheimer disease. AB - Passive immunization with anti-amyloid-beta peptide (Abeta) antibodies is effective in animal models of Alzheimer disease. With the advent of efficient in vitro selection technologies, the novel class of designed ankyrin repeat proteins (DARPins) presents an attractive alternative to the immunoglobulin scaffold. DARPins are small and highly stable proteins with a compact modular architecture ideal for high affinity protein-protein interactions. In this report, we describe the selection, binding profile, and epitope analysis of Abeta-specific DARPins. We further showed their ability to delay Abeta aggregation and prevent Abeta mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in vivo, mono- and trivalent Abeta-specific DARPins (D23 and 3*D23) were infused intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4 weeks. Both D23 and 3*D23 treatments were shown to result in improved cognitive performance and reduced soluble Abeta levels. These findings demonstrate the therapeutic potential of Abeta-specific DARPins for the treatment of Alzheimer disease. PMID- 25118286 TI - High-throughput analysis of ultrasonication-forced amyloid fibrillation reveals the mechanism underlying the large fluctuation in the lag time. AB - Amyloid fibrils form in supersaturated solutions of precursor proteins by a nucleation and growth mechanism characterized by a lag time. Although the lag time provides a clue to understanding the complexity of nucleation events, its long period and low reproducibility have been obstacles for exact analysis. Ultrasonication is known to effectively break supersaturation and force fibrillation. By constructing a Handai amyloid burst inducer, which combines a water bath-type ultrasonicator and a microplate reader, we examined the ultrasonication-forced fibrillation of several proteins, with a focus on the fluctuation in the lag time. Amyloid fibrillation of hen egg white lysozyme was examined at pH 2.0 in the presence of 1.0-5.0 M guanidine hydrochloride (GdnHCl), in which the dominant species varied from the native to denatured conformations. Although fibrillation occurred at various concentrations of GdnHCl, the lag time varied largely, with a minimum being observed at ~3.0 M, the concentration at which GdnHCl-dependent denaturation ended. The coefficient of variation of the lag time did not depend significantly on the GdnHCl concentration and was 2-fold larger than that of the ultrasonication-dependent oxidation of iodide, a simple model reaction. These results suggest that the large fluctuation observed in the lag time for amyloid fibrillation originated from a process associated with a common amyloidogenic intermediate, which may have been a relatively compact denatured conformation. We also suggest that the Handai amyloid burst inducer system will be useful for studying the mechanism of crystallization of proteins because proteins form crystals by the same mechanism as amyloid fibrils under supersaturation. PMID- 25118285 TI - Ubiquitin-specific protease 7 regulates nucleotide excision repair through deubiquitinating XPC protein and preventing XPC protein from undergoing ultraviolet light-induced and VCP/p97 protein-regulated proteolysis. AB - Ubiquitin specific protease 7 (USP7) is a known deubiquitinating enzyme for tumor suppressor p53 and its downstream regulator, E3 ubiquitin ligase Mdm2. Here we report that USP7 regulates nucleotide excision repair (NER) via deubiquitinating xeroderma pigmentosum complementation group C (XPC) protein, a critical damage recognition factor that binds to helix-distorting DNA lesions and initiates NER. XPC is ubiquitinated during the early stage of NER of UV light-induced DNA lesions. We demonstrate that transiently compromising cellular USP7 by siRNA and chemical inhibition leads to accumulation of ubiquitinated forms of XPC, whereas complete USP7 deficiency leads to rapid ubiquitin-mediated XPC degradation upon UV irradiation. We show that USP7 physically interacts with XPC in vitro and in vivo. Overexpression of wild-type USP7, but not its catalytically inactive or interaction-defective mutants, reduces the ubiquitinated forms of XPC. Importantly, USP7 efficiently deubiquitinates XPC-ubiquitin conjugates in deubiquitination assays in vitro. We further show that valosin-containing protein (VCP)/p97 is involved in UV light-induced XPC degradation in USP7-deficient cells. VCP/p97 is readily recruited to DNA damage sites and colocalizes with XPC. Chemical inhibition of the activity of VCP/p97 ATPase causes an increase in ubiquitinated XPC on DNA-damaged chromatin. Moreover, USP7 deficiency severely impairs the repair of cyclobutane pyrimidine dimers and, to a lesser extent, affects the repair of 6-4 photoproducts. Taken together, our findings uncovered an important role of USP7 in regulating NER via deubiquitinating XPC and by preventing its VCP/p97-regulated proteolysis. PMID- 25118287 TI - The Toxoplasma pseudokinase ROP5 is an allosteric inhibitor of the immunity related GTPases. AB - The Red Queen hypothesis proposes that there is an evolutionary arms race between host and pathogen. One possible example of such a phenomenon could be the recently discovered interaction between host defense proteins known as immunity related GTPases (IRGs) and a family of rhoptry pseudokinases (ROP5) expressed by the protozoan parasite, Toxoplasma gondii. Mouse IRGs are encoded by an extensive and rapidly evolving family of over 20 genes. Similarly, the ROP5 family is highly polymorphic and consists of 4-10 genes, depending on the strain of Toxoplasma. IRGs are known to be avidly bound and functionally inactivated by ROP5 proteins, but the molecular basis of this interaction/inactivation has not previously been known. Here we show that ROP5 uses a highly polymorphic surface to bind adjacent to the nucleotide-binding domain of an IRG and that this produces a profound allosteric change in the IRG structure. This has two dramatic effects: 1) it prevents oligomerization of the IRG, and 2) it alters the orientation of two threonine residues that are targeted by the Toxoplasma Ser/Thr kinases, ROP17 and ROP18. ROP5s are highly specific in the IRGs that they will bind, and the fact that it is the most highly polymorphic surface of ROP5 that binds the IRG strongly supports the notion that these two protein families are co evolving in a way predicted by the Red Queen hypothesis. PMID- 25118288 TI - Shock wave treatment enhances cell proliferation and improves wound healing by ATP release-coupled extracellular signal-regulated kinase (ERK) activation. AB - Shock wave treatment accelerates impaired wound healing in diverse clinical situations. However, the mechanisms underlying the beneficial effects of shock waves have not yet been fully revealed. Because cell proliferation is a major requirement in the wound healing cascade, we used in vitro studies and an in vivo wound healing model to study whether shock wave treatment influences proliferation by altering major extracellular factors and signaling pathways involved in cell proliferation. We identified extracellular ATP, released in an energy- and pulse number-dependent manner, as a trigger of the biological effects of shock wave treatment. Shock wave treatment induced ATP release, increased Erk1/2 and p38 MAPK activation, and enhanced proliferation in three different cell types (C3H10T1/2 murine mesenchymal progenitor cells, primary human adipose tissue-derived stem cells, and a human Jurkat T cell line) in vitro. Purinergic signaling-induced Erk1/2 activation was found to be essential for this proliferative effect, which was further confirmed by in vivo studies in a rat wound healing model where shock wave treatment induced proliferation and increased wound healing in an Erk1/2-dependent fashion. In summary, this report demonstrates that shock wave treatment triggers release of cellular ATP, which subsequently activates purinergic receptors and finally enhances proliferation in vitro and in vivo via downstream Erk1/2 signaling. In conclusion, our findings shed further light on the molecular mechanisms by which shock wave treatment exerts its beneficial effects. These findings could help to improve the clinical use of shock wave treatment for wound healing. PMID- 25118289 TI - Regulation of the extrinsic apoptotic pathway by microRNA-21 in alcoholic liver injury. AB - IL-6/Stat3 is associated with the regulation of transcription of key cellular regulatory genes (microRNAs) during different types of liver injury. This study evaluated the role of IL-6/Stat3 in regulating miRNA and miR-21 in alcoholic liver disease. By microarray, we identified that ethanol feeding significantly up regulated 0.8% of known microRNAs in mouse liver compared with controls, including miR-21. Similarly, the treatment of normal human hepatocytes (N-Heps) and hepatic stellate cells (HSCs) with ethanol and IL-6 significantly increased miR-21 expression. Overexpression of miR-21 decreased ethanol-induced apoptosis in both N-Heps and HSCs. The expression level of miR-21 was significantly increased after Stat3 activation in N-Heps and HSCs, in support of the concept that the 5'-promoter region of miR-21 is regulated by Stat3. Using real time PCR, we confirmed that miR-21 activation is associated with ethanol-linked Stat3 binding of the miR-21 promoter. A combination of bioinformatics, PCR array, dual luciferase reporter assay, and Western blot analysis revealed that Fas ligand (TNF superfamily, member 6) (FASLG) and death receptor 5 (DR5) are the direct targets of miR-21. Furthermore, inhibition of miR-21 by specific Vivo-Morpholino and knock-out of IL-6 in ethanol-treated mice also increased the expression of DR5 and FASLG in vivo during alcoholic liver injury. The identification of miR-21 as an important regulator of hepatic cell survival, transformation, and remodeling in vitro, as well as its upstream modulators and downstream targets, will provide insight into the involvement of altered miRNA expression in contributing to alcoholic liver disease progression and testing novel therapeutic approaches for human alcoholic liver diseases. PMID- 25118292 TI - Simpson's paradox: how performance measurement can fail even with perfect risk adjustment. PMID- 25118290 TI - Antiparallel triple-strand architecture for prefibrillar Abeta42 oligomers. AB - Abeta42 oligomers play key roles in the pathogenesis of Alzheimer disease, but their structures remain elusive partly due to their transient nature. Here, we show that Abeta42 in a fusion construct can be trapped in a stable oligomer state, which recapitulates characteristics of prefibrillar Abeta42 oligomers and enables us to establish their detailed structures. Site-directed spin labeling and electron paramagnetic resonance studies provide structural restraints in terms of side chain mobility and intermolecular distances at all 42 residue positions. Using these restraints and other biophysical data, we present a novel atomic-level oligomer model. In our model, each Abeta42 protein forms a single beta-sheet with three beta-strands in an antiparallel arrangement. Each beta sheet consists of four Abeta42 molecules in a head-to-tail arrangement. Four beta sheets are packed together in a face-to-back fashion. The stacking of identical segments between different beta-sheets within an oligomer suggests that prefibrillar oligomers may interconvert with fibrils via strand rotation, wherein beta-strands undergo an ~90 degrees rotation along the strand direction. This work provides insights into rational design of therapeutics targeting the process of interconversion between toxic oligomers and non-toxic fibrils. PMID- 25118291 TI - A sensory complex consisting of an ATP-binding cassette transporter and a two component regulatory system controls bacitracin resistance in Bacillus subtilis. AB - Resistance against antimicrobial peptides in many Firmicutes bacteria is mediated by detoxification systems that are composed of a two-component regulatory system (TCS) and an ATP-binding cassette (ABC) transporter. The histidine kinases of these systems depend entirely on the transporter for sensing of antimicrobial peptides, suggesting a novel mode of signal transduction where the transporter constitutes the actual sensor. The aim of this study was to investigate the molecular mechanisms of this unusual signaling pathway in more detail, using the bacitracin resistance system BceRS-BceAB of Bacillus subtilis as an example. To analyze the proposed communication between TCS and the ABC transporter, we characterized their interactions by bacterial two-hybrid analyses and could show that the permease BceB and the histidine kinase BceS interact directly. In vitro pulldown assays confirmed this interaction, which was found to be independent of bacitracin. Because it was unknown whether BceAB-type transporters could detect their substrate peptides directly or instead recognized the peptide-target complex in the cell envelope, we next analyzed substrate binding by the transport permease, BceB. Direct and specific binding of bacitracin by BceB was demonstrated by surface plasmon resonance spectroscopy. Finally, in vitro signal transduction assays indicated that complex formation with the transporter influenced the autophosphorylation activity of the histidine kinase. Taken together, our findings clearly show the existence of a sensory complex composed of TCS and ABC transporters and provide the first functional insights into the mechanisms of stimulus perception, signal transduction, and antimicrobial resistance employed by Bce-like detoxification systems. PMID- 25118294 TI - Predictive markers of radiotherapy-induced rectal cancer regression. AB - Patients with locally advanced rectal cancer receive preoperative radiotherapy to reduce the probability of recurrence and to possibly improve overall survival. However, this appears dependent on the extent of histological tumour regression seen in the resected bowel, which can be highly variable between individuals. No predictive marker that can stratify patient management in this regard is currently available. Experimental data implicates a variety of factors that are involved in the DNA damage response following radiation injury, tumour tissue oxygenation, autoimmune antitumour response triggered by radiotherapy and in the pathogenesis of colorectal cancer, as potential indicators of radiation sensitivity. These details are presented in this review, which may serve as targets for clinical validation studies aiming to find predictors of radiotherapy response in rectal cancer. PMID- 25118293 TI - Alterations of insulin-like growth factor-1 receptor gene copy number and protein expression are common in non-small cell lung cancer. AB - AIMS: Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase membrane receptor involved in tumourigenesis that may be a potential therapeutic target. We aimed to investigate the incidence and prognostic significance of alterations in IGF1R copy number, and IGF1R protein expression in resected primary non-small cell lung cancer (NSCLC), and lymph node metastases. METHODS: IGF1R gene copy number status was evaluated by chromogenic silver in situ hybridisation and IGF1R protein expression was evaluated by immunohistochemistry in tissue microarray sections from a retrospective cohort of 309 surgically resected NSCLCs and results were compared with clinicopathological features, including EGFR and KRAS mutational status and patient survival. RESULTS: IGF1R gene copy number status was positive (high polysomy or amplification) in 29.2% of NSCLC, and 12.1% exhibited IGF1R gene amplification. High IGF1R expression was found in 28.3%. There was a modest correlation between IGF1R gene copy number and protein expression (r=0.2, p<0.05). Alterations of IGF1R gene copy number and protein expression in primary tumours were significantly associated with alterations in lymph node metastases (p<0.01). High IGF1R gene copy number and protein expression was significantly higher in squamous cell carcinomas (SCC) compared with other subtypes of NSCLC (p<0.05). There were no other associations between IGF1R status and other clinicopathological features including patient age, gender, smoking status, tumour size, stage, grade, EGFR or KRAS mutational status or overall survival. CONCLUSIONS: High IGF1R gene copy number and protein overexpression are frequent in NSCLC, particularly in SCCs, but they are not prognostically relevant. PMID- 25118295 TI - CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma. AB - AIM: Perineural invasion and expression of CXCR4 is characteristic of adenoid cystic carcinoma (ACC). Herein, we aimed to demonstrate CXCR4 expression in ACC, identify its association with perineural invasion and investigate the impact of CXCR4 inhibitor in vitro and in a murine perineural invasion model. METHODS: Expression of CXCR4 was assessed in ACC cell lines and in human tissue. The effects of gene knockdown using siRNA and specific blocker of CXCR4 (AMD3100) were evaluated in vitro. A preclinical perineural invasion model was developed using BALB/c nude mouse. The effect of AMD3100 was evaluated in vivo. RESULTS: CXCR4 was highly expressed in aggressive strains of ACC in vitro, in the tumour in the animal model and in the tumour of human tissue. SDF-1 expression was also demonstrated in the nerve of murine and human tissue. Gene knockdown by siRNA and inhibition by a CXCR4-specific inhibitor AMD3100 effectively abrogated invasion but not proliferation of ACC in vitro. The rate of perineural invasion was significantly decreased with AMD3100 treatment in the animal model. CONCLUSIONS: CXCR4 is associated with perineural invasion in ACC. AMD3100, which can effectively diminish perineural invasion of ACC, may have an adjuvant role in the management of ACC. PMID- 25118296 TI - Leaf mass per area is independent of vein length per area: avoiding pitfalls when modelling phenotypic integration (reply to Blonder et al. 2014). AB - It has been recently proposed that leaf vein length per area (VLA) is the major determinant of leaf mass per area ( MA), and would thereby determine other traits of the leaf economic spectrum (LES), such as photosynthetic rate per mass (A(mass)), nitrogen concentration per mass (N(mass)) and leaf lifespan (LL). In a previous paper we argued that this 'vein origin' hypothesis was supported only by a mathematical model with predestined outcomes, and that we found no support for the 'vein origin' hypothesis in our analyses of compiled data. In contrast to the 'vein origin' hypothesis, empirical evidence indicated that VLA and LMA are independent mechanistically, and VLA (among other vein traits) contributes to a higher photosynthetic rate per area (A(area)), which scales up to driving a higher A(mass), all independently of LMA, N(mass) and LL. In their reply to our paper, Blonder et al. (2014) raised questions about our analysis of their model, but did not address our main point, that the data did not support their hypothesis. In this paper we provide further analysis of an extended data set, which again robustly demonstrates the mechanistic independence of LMA from VLA, and thus does not support the 'vein origin' hypothesis. We also address the four specific points raised by Blonder et al. (2014) regarding our analyses. We additionally show how this debate provides critical guidance for improved modelling of LES traits and other networks of phenotypic traits that determine plant performance under contrasting environments. PMID- 25118297 TI - SUMO1 in human sperm: new targets, role in motility and morphology and relationship with DNA damage. AB - In studies carried out previously, we demonstrated that small ubiquitin-like modifier 1 (SUMO1) is associated with poor sperm motility when evaluated with a protocol that reveals mostly SUMO1-ylated live sperm. Recently, with another protocol, it has been demonstrated that SUMO is expressed in most sperm and is related to poor morphology and motility, suggesting that sumoylation may have multiple roles depending on its localisation and targets. We show herein, by confocal microscopy and co-immunoprecipitation, that dynamin-related protein 1 (DRP1), Ran GTPase-activating protein 1 (RanGAP1) and Topoisomerase IIalpha, SUMO1 targets in somatic and/or germ cells, are SUMO1-ylated in mature human spermatozoa. DRP1 co-localises with SUMO1 in the mid-piece, whereas RanGAP1 and Topoisomerase IIalpha in the post-acrosomal region of the head. Both SUMO1 expression and co-localisation with the three proteins were significantly higher in morphologically abnormal sperm, suggesting that sumoylation represents a marker of defective sperm. DRP1 sumoylation at the mid-piece level was higher in the sperm of asthenospermic men. As in somatic cells, DRP1 sumoylation is associated with mitochondrial alterations, this protein may represent the link between SUMO and poor motility. As SUMO pathways are involved in responses to DNA damage, another aim of our study was to investigate the relationship between sumoylation and sperm DNA fragmentation (SDF). By flow cytometry, we demonstrated that SUMO1-ylation and SDF are correlated (r=0.4, P<0.02, n=37) and most sumoylated sperm shows DNA damage in co-localisation analysis. When SDF was induced by stressful conditions (freezing and thawing and oxidative stress), SUMO1-ylation increased. Following freezing and thawing, SUMO1-Topoisomerase IIalpha co-localisation and co-immunoprecipitation increased, suggesting an involvement in the formation/repair of DNA breakage. PMID- 25118298 TI - CAR expression in human embryos and hESC illustrates its role in pluripotency and tight junctions. AB - Coxsackie virus and adenovirus receptor, CXADR (CAR), is present during embryogenesis and is involved in tissue regeneration, cancer and intercellular adhesion. We investigated the expression of CAR in human preimplantation embryos and embryonic stem cells (hESC) to identify its role in early embryogenesis and differentiation. CAR protein was ubiquitously present during preimplantation development. It was localised in the nucleus of uncommitted cells, from the cleavage stage up to the precursor epiblast, and corresponded with the presence of soluble CXADR3/7 splice variant. CAR was displayed on the membrane, involving in the formation of tight junction at compaction and blastocyst stages in both outer and inner cells, and CAR corresponded with the full-length CAR-containing transmembrane domain. In trophectodermal cells of hatched blastocysts, CAR was reduced in the membrane and concentrated in the nucleus, which correlated with the switch in RNA expression to the CXADR4/7 and CXADR2/7 splice variants. The cells in the outer layer of hESC colonies contained CAR on the membrane and all the cells of the colony had CAR in the nucleus, corresponding with the transmembrane CXADR and CXADR4/7. Upon differentiation of hESC into cells representing the three germ layers and trophoblast lineage, the expression of CXADR was downregulated. We concluded that CXADR is differentially expressed during human preimplantation development. We described various CAR expressions: i) soluble CXADR marking undifferentiated blastomeres; ii) transmembrane CAR related with epithelial-like cell types, such as the trophectoderm (TE) and the outer layer of hESC colonies; and iii) soluble CAR present in TE nuclei after hatching. The functions of these distinct forms remain to be elucidated. PMID- 25118299 TI - Expression, activation, and role of AKT isoforms in the uterus. AB - The three isoforms of AKT: AKT1, AKT2, and AKT3, are crucial regulators of both normal and pathological cellular processes. Each of these isoforms exhibits a high level of homology and functional redundancy with each other. However, while being highly similar and structurally homologous, a rising amount of evidence is showing that each isoform possesses specific targets as well as preferential subcellular localization. The role of AKT has been studied extensively in reproductive processes, but isoform-specific roles are yet to be fully understood. This review will focus on the role of AKT in the uterus and its function in processes related to cell death and proliferation such as embryo implantation, decidualization, endometriosis, and endometrial cancer in an isoform-centric manner. In this review, we will cover the activation of AKT in various settings, localization of isoforms in subcellular compartments, and the effect of isoform expression on cellular processes. To fully understand the dynamic molecular processes taking place in the uterus, it is crucial that we better understand the physiological role of AKT isoforms as well as their function in the emergence of diseases. PMID- 25118300 TI - Haplo-deficiency of ODF1/HSPB10 in mouse sperm causes relaxation of head-to-tail linkage. AB - The small heat shock protein ODF1/HSPB10 is essential for male fertility in mice. Targeted deletion of Odf1 resulted in acephalic sperm in homozygous mice of mixed background (C57BL/6J//129/Sv), whereas heterozygous animals are fully fertile. To further elucidate the function of ODF1, we generated incipient congenic mice with targeted deletion of Odf1 by successive backcrossing on the 129/Sv background. We observed that fecundity of heterozygous Odf1(+/-) male mice was severely reduced over backcross generations. However, neither aberrant sperm parameters nor sperm anomalies could be observed. Ultra-structural analyses of sperm from incipient congenic heterozygous Odf1(+/-) males of backcross generation N7 revealed no obvious pathological findings. However, we observed an enlargement of the distance between nuclear membrane and capitulum, indicating a weakening of the sperm head-to-tail coupling. Severe male subfertility provoked by haplo deficiency of ODF1 is therefore most probably caused by impaired head-to-tail coupling that eventually might induce sperm decapitation on the specific conditions of in vivo fertilisation. As subfertility in haplo-deficient ODF1 male mice could not be diagnosed by semen analysis, it seems to be a paradigm for unexplained infertility that is a frequent diagnosis for male fertility impairment in humans. PMID- 25118301 TI - Seminal plasma aids the survival and cervical transit of epididymal ram spermatozoa. AB - Seminal plasma purportedly plays a critical role in reproduction, but epididymal spermatozoa are capable of fertilisation following deposition in the uterus, calling into question the biological requirement of this substance. Through a combination of direct observation of spermatozoa in utero using probe-based Confocal Laser Endomicroscopy, in vivo assessment of sperm fertility and in vitro analysis of various sperm functional parameters, this study investigated the role of seminal plasma in spermatozoa transit through the cervix of the ewe. Following deposition in the cervical os, epididymal spermatozoa previously exposed to seminal plasma displayed an enhanced ability to traverse the cervix as evidenced by both significantly higher pregnancy rates and numbers of spermatozoa observed at the utero-tubal junction when compared with epididymal spermatozoa not previously exposed to seminal plasma. The beneficial effect of seminal plasma on sperm transport was clearly localised to transit through the cervix as pregnancy rates of spermatozoa deposited directly into the uterus were unaffected by exposure to seminal plasma. This phenomenon was not explained by changes to sperm motion characteristics, as seminal plasma had no effect on the motility, kinematic parameters or mitochondrial membrane potential of spermatozoa. Rather, in vitro testing revealed that seminal plasma improved the ability of epididymal spermatozoa to penetrate cervical mucus recovered from ewes in oestrus. These results demonstrate that the survival and transport of ram spermatozoa through the cervix of the ewe is not linked to their motility or velocity but rather the presence of some cervical penetration trait conferred by exposure to seminal plasma. PMID- 25118302 TI - Individual commitment to a group effect: strengths and weaknesses of bovine embryo group culture. AB - Recently, new culture devices such as Corral and Primo Vision dishes have been designed for the culture of human embryos to allow the combination of group culture plus follow-up of individual embryos. Bovine inseminated oocytes were allocated to Primo Vision dishes, Corral dishes, individual culture or classical group culture. Blastocyst development in Primo Vision dishes was similar to classical group culture (34.3 and 39.0% respectively), and better than Corral dishes or individual culture (28.9 and 28.5% respectively). In Primo Vision dishes, a higher number of 'slow' embryos developed to the blastocyst stage compared with their individually cultured counterparts, while no differences were observed for 'fast' embryos. 'Slow' embryos in a 'standard drop' had a higher chance of becoming a blastocyst compared with individual culture (OR: 2.3), whereas blastulation of 'fast' embryos was less efficient in a 'delayed drop' than in individual culture (OR: 0.3). The number of non-cleaved embryos in Primo Vision dishes did not negatively influence blastocyst development. Likewise, removing non-cleaved embryos (NC removed) and regrouping the cleaved embryos afterwards (ReGR) did not affect blastocyst development and quality compared with group culture in Primo Vision dishes (CTRL, 31.6%, NC removed, 29.3% and ReGR, 29.6%). The experiments revealed that group culture of bovine embryos in Primo Vision dishes is superior to individual culture, primarily because of the higher blastocyst rate achieved by slow embryos. Non-cleaved or arrested embryos do not hamper the ability of co-cultured bovine embryos to reach the blastocyst stage in group culture. PMID- 25118303 TI - Lamin A/C proteins in the spermatid acroplaxome are essential in mouse spermiogenesis. AB - Spermiogenesis is a complex process of terminal differentiation that is necessary to produce mature sperm. Using protein expression profiles of mouse and human testes generated from our previous studies, we chose to examine the actions of lamin A/C in the current investigation. Lamin A and lamin C are isoforms of the A type lamins that are encoded by the LMNA gene. Our results showed that lamin A/C was expressed in the mouse testis throughout the different stages of spermatogenesis and in mature sperm. Lamin A/C was also expressed in mouse haploid germ cells and was found to be localized to the acroplaxome in spermiogenesis, from round spermatids until mature spermatozoa. The decreased expression of lamin A/C following injections of siRNA against Lmna caused a significant increase in caudal sperm head abnormalities when compared with negative controls. These abnormalities were characterized by increased fragmentation of the acrosome and abnormal vesicles, which failed to fuse to the developing acrosome. This fragmentation also caused significant alterations in nuclear elongation and acrosome formation. Furthermore, we found that lamin A/C interacted with the microtubule plus-end-tracking protein CLIP170. These results suggest that lamin A/C is critical for proper structural and functional development of the sperm acrosome and head shape. PMID- 25118304 TI - Expression and regulation of the tumor suppressor, SEF, during folliculogenesis in humans and mice. AB - Similar expression to FGF (Sef or IL17-RD), is a tumor suppressor and an inhibitor of growth factors as well as of pro-inflammatory cytokine signaling. In this study, we examined the regulation of Sef expression by gonadotropins during ovarian folliculogenesis. In sexually immature mice, in situ hybridization (ISH) localized Sef gene expression to early developing oocytes and granulosa cells (GC) but not to theca cells. Sef was also expressed in mouse ovarian endothelial cells, in the fallopian tube epithelium as well as in adipose tissue venules. SEF protein expression, determined by immunohistochemistry (IHC), correlated well with Sef mRNA expression in GC, while differential expression was noticed in oocytes. High Sef mRNA but undetectable SEF protein levels were observed in the oocytes of primary/secondary follicles, while an inverse correlation was found in the oocytes of preantral and small antral follicles. Sef mRNA expression dropped after pregnant mare's serum gonadotropin (PMSG) administration, peaked at 6-8 h after human chorionic gonadotropin (hCG) treatment, and declined by 12 h after this treatment. ISH and IHC localized the changes to oocytes and mural GC following PMSG treatment, whereas Sef expression increased in mural GC and declined in granulosa-lutein cells upon hCG treatment. The ovarian expression of SEF was confirmed using human samples. ISH localized SEF transcripts to human GC of antral follicles but not to corpora lutea. Furthermore, SEF mRNA was detected in human GC recovered from preovulatory follicles. These results are the first to demonstrate SEF expression in a healthy ovary during folliculogenesis. Hormonal regulation of its expression suggests that SEF may be an important factor involved in intra-ovarian control mechanisms. PMID- 25118305 TI - Comparison of Therapist-Directed and Physician-Directed Respiratory Care in COPD Subjects With Acute Pneumonia. AB - BACKGROUND: The purpose of this retrospective medical record review was to compare the effects of therapist-directed (protocol RT) and physician-directed (non-protocol RT) respiratory therapy on hospital stay and 30-d post-discharge readmission in COPD subjects with acute bacterial pneumonia. METHODS: We reviewed 320 medical records; 244 records were usable. Information gathered included gender, age, RT protocol type (protocol RT or non-protocol RT), hospital stay, 30 d post-discharge readmission, and disease severity score. A 3-way analysis of variance and post hoc analysis were performed to determine the possible effects of disease severity, age, and RT protocol type on hospital stay and the possible interaction effects among these independent variables. A chi-square test for independence was computed to determine whether there was an association between RT protocol type and 30-d readmission. RESULTS: There were no significant interaction effects among RT protocol type, age, and disease severity on hospital stay. In addition, there were no significant effects of either RT protocol type (P=.41) or age (P=.85) on hospital stay in our subject sample. However, as expected, disease severity had a significant effect on hospital stay, increasing it by a mean of 2.6 d (95% CI 0.77-4.4, P=.005). The chi-square test for independence revealed that the frequency of 30-d readmission was significantly associated with RT protocol type (P=.02); fewer 30-d readmissions were associated with protocol RT. CONCLUSIONS: We interpreted the finding of no difference in mean hospital stay between protocol and non-protocol RT to indicate that protocol RT did not confer a disadvantage to subjects in terms of hospital stay. Additionally, the results suggest that treatment efficacy is not sacrificed when RT is directed by respiratory therapists rather than by physicians regardless of disease severity and that therapist-directed protocols may have been of some benefit in reducing 30-d post-discharge readmission. PMID- 25118306 TI - Neonatal and adult ICU ventilators to provide ventilation in neonates, infants, and children: a bench model study. AB - BACKGROUND: Using a bench test model, we investigated the hypothesis that neonatal and/or adult ventilators equipped with neonatal/pediatric modes currently do not reliably administer pressure support (PS) in neonatal or pediatric patient groups in either the absence or presence of air leaks. METHODS: PS was evaluated in 4 neonatal and 6 adult ventilators using a bench model to evaluate triggering, pressurization, and cycling in both the absence and presence of leaks. Delivered tidal volumes were also assessed. Three patients were simulated: a preterm infant (resistance 100 cm H2O/L/s, compliance 2 mL/cm H2O, inspiratory time of the patient [TI] 400 ms, inspiratory effort 1 and 2 cm H2O), a full-term infant (resistance 50 cm H2O/L/s, compliance 5 mL/cm H2O, TI 500 ms, inspiratory effort 2 and 4 cm H2O), and a child (resistance 30 cm H2O/L/s, compliance 10 mL/cm H2O, TI 600 ms, inspiratory effort 5 and 10 cm H2O). Two PS levels were tested (10 and 15 cm H2O) with and without leaks and with and without the leak compensation algorithm activated. RESULTS: Without leaks, only 2 neonatal ventilators and one adult ventilator had trigger delays under a given predefined acceptable limit (1/8 TI). Pressurization showed high variability between ventilators. Most ventilators showed TI in excess high enough to seriously impair patient-ventilator synchronization (> 50% of the TI of the subject). In some ventilators, leaks led to autotriggering and impairment of ventilation performance, but the influence of leaks was generally lower in neonatal ventilators. When a noninvasive ventilation algorithm was available, this was partially corrected. In general, tidal volume was calculated too low by the ventilators in the presence of leaks; the noninvasive ventilation algorithm was able to correct this difference in only 2 adult ventilators. CONCLUSIONS: No ventilator performed equally well under all tested conditions for all explored parameters. However, neonatal ventilators tended to perform better in the presence of leaks. These findings emphasize the need to improve algorithms for assisted ventilation modes to better deal with situations of high airway resistance, low pulmonary compliance, and the presence of leaks. PMID- 25118307 TI - Subjects hospitalized with the 2009 pandemic influenza A (H1N1) virus in a respiratory infection unit: clinical factors correlating with ICU admission. AB - BACKGROUND: The 2009 pandemic influenza A (H1N1) virus was accompanied by high morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with documented 2009 influenza A (H1N1) virus admitted to a reference chest hospital, the disease outcome, and risk factors associated with ICU admission. METHODS: We assessed 109 subjects admitted to the respiratory infection unit of a hospital for chest disease with signs and symptoms of the 2009 influenza A (H1N1) virus between April 2009 and December 2010. Demographic data, comorbidities, clinical signs and symptoms, laboratory tests, radiographic findings, treatment, and final outcomes were all recorded. Factors associated with severe disease requiring ICU admission were determined. RESULTS: Ninety subjects (82.5%) had laboratory-confirmed 2009 influenza A (H1N1). Sixty-four percent of these subjects had pneumonia on admission, 26% had respiratory failure, and 11% required care in the ICU. Dyspnea and the presence of infiltrates on chest x-rays were the most common signs among the subjects with H1N1. All subjects were treated with antiviral therapy, and 75% received antibiotic treatment based on their clinical and laboratory findings. The predictive factors of ICU admission were severe hypoxemia and lymphocytosis. CONCLUSIONS: The outcome of subjects with influenza A (H1N1) virus infection was influenced by the severity of the disease on admission, the subjects' underlying conditions, and complications during hospitalization. PMID- 25118308 TI - Use of heliox delivered via high-flow nasal cannula to treat an infant with coronavirus-related respiratory infection and severe acute air-flow obstruction. AB - Heliox, a helium-oxygen gas mixture, has been used for many decades to treat obstructive pulmonary disease. The lower density and higher viscosity of heliox relative to nitrogen-oxygen mixtures can significantly reduce airway resistance when an anatomic upper air-flow obstruction is present and gas flow is turbulent. Clinically, heliox can decrease airway resistance in acute asthma in adults and children and in COPD. Heliox may also enhance the bronchodilating effects of beta agonist administration for acute asthma. Respiratory syndromes caused by coronavirus infections in humans range in severity from the common cold to severe acute respiratory syndrome associated with human coronavirus OC43 and other viral strains. In infants, coronavirus infection can cause bronchitis, bronchiolitis, and pneumonia in variable combinations and can produce enough air-flow obstruction to cause respiratory failure. We describe a case of coronavirus OC43 infection in an infant with severe acute respiratory distress treated with heliox inhalation to avoid intubation. PMID- 25118309 TI - A taxonomy for mechanical ventilation: 10 fundamental maxims. AB - The American Association for Respiratory Care has declared a benchmark for competency in mechanical ventilation that includes the ability to "apply to practice all ventilation modes currently available on all invasive and noninvasive mechanical ventilators." This level of competency presupposes the ability to identify, classify, compare, and contrast all modes of ventilation. Unfortunately, current educational paradigms do not supply the tools to achieve such goals. To fill this gap, we expand and refine a previously described taxonomy for classifying modes of ventilation and explain how it can be understood in terms of 10 fundamental constructs of ventilator technology: (1) defining a breath, (2) defining an assisted breath, (3) specifying the means of assisting breaths based on control variables specified by the equation of motion, (4) classifying breaths in terms of how inspiration is started and stopped, (5) identifying ventilator-initiated versus patient-initiated start and stop events, (6) defining spontaneous and mandatory breaths, (7) defining breath sequences (8), combining control variables and breath sequences into ventilatory patterns, (9) describing targeting schemes, and (10) constructing a formal taxonomy for modes of ventilation composed of control variable, breath sequence, and targeting schemes. Having established the theoretical basis of the taxonomy, we demonstrate a step-by-step procedure to classify any mode on any mechanical ventilator. PMID- 25118310 TI - Extracorporeal membrane oxygenation for refractory air leak in a child presenting with bacterial tracheitis. PMID- 25118311 TI - Asthma and adherence to inhaled corticosteroids: current status and future perspectives. AB - Inhaled corticosteroids (ICS) are the cornerstone of maintenance asthma therapy. However, in spite of this, adherence to ICS remains low. The aim of this systematic literature review was to provide an overview of the current knowledge of adherence to ICS, effects of poor adherence, and means to improve adherence. A total of 19 studies met the inclusion criteria: 9 focusing on the level of adherence, 6 focusing on effects of poor adherence, and 7 focusing on interventions to improve adherence. Three of the studies focused on more than one of these end points. The mean level of adherence to ICS was found to be between 22 and 63%, with improvement up to and after an exacerbation. Poor adherence was associated with youth, being African-American, having mild asthma, < 12 y of formal education, and poor communication with the health-care provider, whereas improved adherence was associated with being prescribed fixed-combination therapy (ICS and long-acting beta2 agonists). Good adherence was associated with higher FEV1, a lower percentage of eosinophils in sputum, reduction in hospitalizations, less use of oral corticosteroids, and lower mortality rate. Overall, 24% of exacerbations and 60% of asthma-related hospitalizations could be attributed to poor adherence. Most studies have reported an increase in adherence following focused interventions, followed by an improvement in quality of life, symptoms, FEV1, and oral corticosteroid use. However, 2 studies found no difference in health-care utilization, one observed no effect on symptoms, and one observed more symptoms in subjects in the intervention group compared with the control group. Good adherence to ICS in asthma improves outcome but remains low. Interventions to improve adherence show varying results, with most studies reporting an increase in adherence but unfortunately not necessarily an improvement in outcome. Even following successful interventions, adherence remains low. Further research is needed to explore barriers to adherence and interventions for improvement. PMID- 25118312 TI - Effects of different levels of pressure support on intra-individual breath-to breath variability. AB - BACKGROUND: Evidence exists that during pressure support ventilation (PSV), the addition of an extrinsic (ie, ventilator-generated) breath-to-breath variability (BBV) of breathing pattern improves respiratory function. If BBV is beneficial per se, choosing the PS level that maximizes it could be considered a valid strategy for conventional PSV. In this study, we evaluated the effect of different PS levels on intrinsic BBV in acutely ill, mechanically ventilated subjects to determine whether a significant relationship exists between PS level and BBV magnitude. METHODS: Fourteen invasively mechanically ventilated subjects were prospectively studied. PS was adjusted at 20 cm H2O and sequentially reduced to 15, 10, and 5 cm H2O. Arterial blood gas analysis and pressure at 0.1 s after the onset of inspiration (P0.1) were measured at each PS level. Airway and esophageal pressure and air flow were continuously recorded. Peak inspiratory flow, tidal volume (VT), breathing frequency, and pressure-time product (PTP) were calculated on a breath-by-breath basis. The breathing pattern variability was assessed by the coefficient of variation of the time series of VT, peak inspiratory flow, and breathing frequency from ~ 60 consecutive breath cycles at each PS level. A general linear model for repeated measures was applied, with PS as an independent factor. A significance level of .05 was considered. RESULTS: Despite a large inter-individual difference in all measured variables (P < .001), the coefficient of variation was as low as 30%, and no significant differences in the coefficient of variation of peak inspiratory flow, breathing frequency, and VT between PS levels were observed (P > .15). Additionally, a significant increase in P0.1, PTP, and breathing frequency (P < .01) and a reduction in VT (P < .001) were observed with PS reduction. CONCLUSIONS: Despite a significant increase in spontaneous activity with PS reduction, BBV was not influenced by the PS level and was as low as 30% for all evaluated parameters. PMID- 25118314 TI - Gender-specific differences in Adamantiades-Behcet's disease manifestations: an analysis of the German registry and meta-analysis of data from the literature. AB - OBJECTIVE: We investigated the effect of gender on the clinical Adamantiades Behcet's disease (ABD) phenotype with data from the German ABD registry and a meta-analysis from a systematic literature review. METHODS: Using the German ABD registry data, we compared 36 clinical variables by gender (with women as the reference category) and investigated potential effect modification by HLA-B5 or ethnic background. The registry data were combined with those from a literature search to calculate pooled relative risks (RRs) for variables with data from >=10 relevant datasets. RESULTS: The German ABD registry provided information for 747 subjects (58.1% males) and the systematic literature review identified another 52 datasets informing on 16 variables. Both analyses consistently revealed the association of male gender with ocular involvement (RR 1.28 and 1.34 from the ABD registry and meta-analysis, respectively), folliculitis (RR 1.30 and 1.26), papulopustular lesions (RR 1.23 and 1.25), vascular involvement (RR 2.31 and 2.27), superficial (RR 2.96 and 1.63) and deep venous thromboses (RR 2.56 and 2.16) and female gender with genital ulcers (RR 0.78 and 0.92) and joint involvement (RR 0.79 and 0.89). The ABD registry data additionally showed male gender associated with heart involvement (RR 10.60), whereas the meta-analyses revealed male gender associated with the pathergy test (RR 1.14) and female gender associated with erythema nodosum (RR 0.86). HLA-B5 and Turkish or German origin did not affect the observed associations. CONCLUSION: These analyses support gender-associated clinical variations in ABD and in particular a clinically meaningful risk of cardiovascular involvement for men. PMID- 25118315 TI - The role of ultrasound in the diagnosis and management of carpal tunnel syndrome: a new paradigm. AB - Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, affecting 9% of women, and it is responsible for significant morbidity and occupational absence. Clinical assessment is used for initial diagnosis and nerve conduction (NC) studies are currently the principal test used to confirm the diagnosis. Sensitivity of NC studies is >85% and specificity is >95%. There is now good evidence that US can be used as an alternative to NC studies to diagnose CTS. US can assess the anatomy of the median nerve and also identify pathology of the surrounding structures that may compress the nerve. Median nerve enlargement (cross-sectional area >=10 mm(2) at the level of the pisiform bone or tunnel inlet) is the most commonly used parameter to diagnose CTS on US, and sensitivity has been reported to be as high as 97.9% using this parameter. US may also be used to guide therapeutic corticosteroid injection into the carpal tunnel--thus avoiding median nerve injury--and to objectively monitor the response to treatment. There is now sufficient evidence to propose a new paradigm for the diagnosis of CTS that incorporates US. US is proposed as the initial diagnostic test in CTS based on similar sensitivity and specificity to NC studies but higher patient acceptability, lower cost and additional capability to assess carpal tunnel anatomy and guide injection. PMID- 25118316 TI - Vocal fold bamboo nodes in undifferentiated connective tissue disease. PMID- 25118313 TI - Methotrexate-mediated inhibition of nuclear factor kappaB activation by distinct pathways in T cells and fibroblast-like synoviocytes. AB - OBJECTIVES: Nuclear factor kappaB (NF-kappaB) is a critical activator of inflammatory processes and MTX is one of the most commonly prescribed DMARDs for treatment of RA. We sought to determine whether MTX inhibited NF-kappaB activity in RA and in lymphocytes and fibroblast-like synoviocytes (FLSs) and to define underlying mechanisms of action. METHODS: An NF-kappaB luciferase reporter plasmid was used to measure NF-kappaB activation across experimental stimuli. Flow cytometry was used to quantify changes in intracellular protein levels, measure levels of reactive oxygen species and determine apoptosis. Quantitative RT-PCR was used to identify changes in MTX target genes. RESULTS: In T cell lines, MTX (0.1 MUM) inhibited activation of NF-kappaB via depletion of tetrahydrobiopterin (BH4) and increased Jun-N-terminal kinase (JNK)-dependent p53 activity. Inhibitors of BH4 activity or synthesis also inhibited NF-kappaB activation and, similar to MTX, increased JNK, p53, p21 and JUN activity. Patients with RA expressed increased levels of phosphorylated or active RelA (p65) compared with controls. Levels of phosphorylated RelA were reduced in patients receiving low-dose MTX therapy. In contrast, inhibition of NF-kappaB activation by MTX was not mediated via BH4 depletion and JNK activation in FLSs, but rather was completely prevented by adenosine receptor antagonists. CONCLUSION: Our findings support a model whereby distinct pathways are activated by MTX in T cells and FLSs to inhibit NF-kappaB activation. PMID- 25118319 TI - Standards for the management of sexually transmitted infections--2014. PMID- 25118318 TI - The first gamma-H2AX biodosimetry intercomparison exercise of the developing European biodosimetry network RENEB. AB - In the event of a mass casualty radiation incident, the gamma-H2AX foci assay could be a useful tool to estimate radiation doses received by individuals. The rapid processing time of blood samples of just a few hours and the potential for batch processing, enabling high throughput, make the assay ideal for early triage categorisation to separate the 'worried well' from the low and critically exposed by quantifying radiation-induced foci in peripheral blood lymphocytes. Within the RENEB framework, 8 European laboratories have taken part in the first European gamma-H2AX biodosimetry exercise, which consisted of a telescoring comparison of 200 circulated foci images taken from 8 samples, and a comparison of 10 fresh blood lymphocyte samples that were shipped overnight to participating labs 4 or 24 h post-exposure. Despite large variations between laboratories in the dose response relationship for foci induction, the obtained results indicate that the network should be able to use the gamma-H2AX assay for rapidly identifying the most severely exposed individuals within a cohort who could then be prioritised for accurate chromosome dosimetry. PMID- 25118320 TI - The utility of cerebrospinal fluid analysis in the investigation and treatment of neurosyphilis. PMID- 25118321 TI - Providing a genitourinary medicine colposcopy service. PMID- 25118322 TI - Diagnostics within the clinic to test for gonorrhoea and chlamydia reduces the time to treatment: a service evaluation. PMID- 25118323 TI - Prevalence of and factors mediating HIV infection among sex workers in Lisbon, Portugal: the 5-year experience of a community organisation. PMID- 25118324 TI - Psychosocial and sexual healthcare needs in men selling sex in Glasgow: a retrospective case note review. PMID- 25118325 TI - Syphilis: a historical vignette. PMID- 25118326 TI - Lipocalin 2 as a membrane-reorganizing agent. AB - Lipocalins are a class of proteins that scavenge hydrophobic molecules in diverse contexts, including the immune system, the nervous system, and cancer. A recent study by Watanbe et al. identifies lipocalin 2 produced by the female mouse reproductive tract as a sperm-capacitating agent that alters the membrane properties of sperm in preparation for fertilization. The potential for lipocalins to act as general modulators of plasma membrane bioactivity is discussed. PMID- 25118329 TI - The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice. AB - Maintenance of an appropriate number of plasma cells, long-lived antibody producing cells that are derived from B cells, is essential for maintaining immunological memory while limiting disease. Plasma cell survival relies on extrinsic factors, the limited availability of which determines the size of the plasma cell population. Mice deficient in the nonreceptor tyrosine kinase Lyn are prone to an autoimmune disease that is characterized by inflammation and an excess of plasma cells (plasmacytosis). We demonstrated that the plasmacytosis was intrinsic to B cells and independent of inflammation. We also showed that Lyn attenuated signaling by signal transducer and activator of transcription 3 (STAT3) and STAT5 in response to the cytokines interleukin-6 (IL-6) and IL-3, respectively, in two previously uncharacterized plasma cell signaling pathways. Thus, in the absence of Lyn, the survival of plasma cells was improved, which enabled the plasma cells to become established in excess numbers in niches in vivo. These data identify Lyn as a key regulator of survival signaling in plasma cells, limiting plasma cell accumulation and autoimmune disease susceptibility. PMID- 25118331 TI - Commentary on: the oncoplastic reduction approach to breast conservation therapy: benefits for margin control. PMID- 25118328 TI - Type IV collagen is an activating ligand for the adhesion G protein-coupled receptor GPR126. AB - GPR126 is an orphan heterotrimeric guanine nucleotide-binding protein (G protein) coupled receptor (GPCR) that is essential for the development of diverse organs. We found that type IV collagen, a major constituent of the basement membrane, binds to Gpr126 and activates its signaling function. Type IV collagen stimulated the production of cyclic adenosine monophosphate in rodent Schwann cells, which require Gpr126 activity to differentiate, and in human embryonic kidney (HEK) 293 cells expressing exogenous Gpr126. Type IV collagen specifically bound to the extracellular amino-terminal region of Gpr126 containing the CUB (complement, Uegf, Bmp1) and pentraxin domains. Gpr126 derivatives lacking the entire amino terminal region were constitutively active, suggesting that this region inhibits signaling and that ligand binding relieves this inhibition to stimulate receptor activity. A new zebrafish mutation that truncates Gpr126 after the CUB and pentraxin domains disrupted development of peripheral nerves and the inner ear. Thus, our findings identify type IV collagen as an activating ligand for GPR126, define its mechanism of activation, and highlight a previously unrecognized signaling function of type IV collagen in basement membranes. PMID- 25118330 TI - Low-dose CT for patients with clinically suspected acute appendicitis: optimal strength of sinogram affirmed iterative reconstruction for image quality and diagnostic performance. AB - BACKGROUND: As there is increased concern over the radiation exposure particularly in adolescents and young adults, computed tomography (CT) dose reduction is needed in the diagnosis of acute appendicitis. PURPOSE: To evaluate the optimal strength of sinogram affirmed iterative reconstruction (SAFIRE) to obtain the best image quality on a 30-mAs applied low-dose CT (LDCT 30mAs) and to compare the diagnostic performances of the LDCT 30mAs with different SAFIRE strengths with that of the 100-mAs applied LDCT (LDCT 100mAs) for the diagnosis of acute appendicitis. MATERIAL AND METHODS: A total of 102 consecutive patients (47 men, 55 women; mean age, 41.2 years; range, 15-82 years) with right lower quadrant pain underwent abdominal-pelvic CT, consisting of arterial phase LDCT 100mAs and portal venous phase LDCT30mAs under a fixed 120 kV. LDCT 30mAs images were reconstructed separately with five strength levels (S1-S5). Two blinded radiologists recorded scores for the subjective image quality of the LDCT 30mAs dataset (S0-S5) and confidence scores for the diagnosis of acute appendicitis on each dataset and LDCT 100mAs. CT image noise was measured for each set. RESULTS: The study population consisted of 58 patients with confirmed appendicitis and 44 without appendicitis. There was no significant difference in diagnostic performance between LDCT 100mAs and LDCT 30mAs with any strength for both readers (AUC for reader 1, LDCT 30mAs with S0-S5 = 0.97, LDCT 100mAs = 0.93, P = 0.0936; for reader 2, LDCT 30mAs with S0-S5 = 0.96, LDCT 100mAs = 0.97, P = 0.128). The measured noise decreased as the strength increased from S0 to S5 (mean, 20.8 > 17.7 > 15.6 > 13.5 > 11.5 > 9.5, P < 0.0001). However, overall subjective image quality on S3 was better than the other strengths for both readers (S0 < S1 < S2 < S3 > S4 > S5, P < 0.0001). CONCLUSION: Although measured noise declined as SAFIRE strength increased, S3 seems optimal for the best subjective image quality on LDCT 30mAs. The diagnostic performance of LDCT 30mAs with any strength is comparable to that of LDCT 100mAs for the diagnosis of acute appendicitis. PMID- 25118327 TI - Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFalpha in glioblastoma. AB - Grade IV glioblastoma is characterized by increased kinase activity of epidermal growth factor receptor (EGFR); however, EGFR kinase inhibitors have failed to improve survival in individuals with this cancer because resistance to these drugs often develops. We showed that tumor necrosis factor-alpha (TNFalpha) produced in the glioblastoma microenvironment activated atypical protein kinase C (aPKC), thereby producing resistance to EGFR kinase inhibitors. Additionally, we identified that aPKC was required both for paracrine TNFalpha-dependent activation of the transcription factor nuclear factor kappaB (NF-kappaB) and for tumor cell-intrinsic receptor tyrosine kinase signaling. Targeting aPKC decreased tumor growth in mouse models of glioblastoma, including models of EGFR kinase inhibitor-resistant glioblastoma. Furthermore, aPKC abundance and activity were increased in human glioblastoma tumor cells, and high aPKC abundance correlated with poor prognosis. Thus, targeting aPKC might provide an improved molecular approach for glioblastoma therapy. PMID- 25118332 TI - Insulin treatment prevents the increase in D-serine in hippocampal CA1 area of diabetic rats. AB - PURPOSE: Diabetes is a high risk factor for dementia. Employing a diabetic rat model, the present study was designed to determine whether the content of D serine (D-Ser) in hippocampus is associated with the impairment of spatial learning and memory ability. METHODS: Diabetes was induced by a single intravenous injection of streptozotocin (STZ). The insulin treatment began 3 days after STZ injection. RESULTS: We found that both water maze learning and hippocampal CA1 long-term potentiation (LTP) were impaired in diabetic rats. The contents of glutamate, D-Ser, and serine racemase in the hippocampus of diabetic rats were significantly higher than those in the control group. Insulin treatment prevented the STZ-induced impairment in water maze learning and hippocampal CA1 LTP in diabetic rats and also maintained the contents of glutamate, D-Ser, and serine racemase at the normal range in hippocampus. CONCLUSIONS: These results suggest that insulin treatment has a potent protection effect on CA1-LTP, spatial learning and memory ability of the diabetic rats in vivo. Furthermore, insulin may take effect by inhibiting the overactivation of N-methyl-d-aspartate receptors, which play a critical role in neurotoxicity. PMID- 25118333 TI - Evaluation of a pet-assisted living intervention for improving functional status in assisted living residents with mild to moderate cognitive impairment: a pilot study. AB - BACKGROUND: In older adults with cognitive impairment (CI), decreased functional status and increased behavioral symptoms require relocation from assisted living (AL) to nursing homes. Studies support positive effects of pets on health/function. PURPOSE: Evaluate the effectiveness of the Pet AL (PAL) intervention to support physical, behavioral, and emotional function in AL residents with CI. METHODS: Cognitively impaired AL residents randomized to 60-90 minute sessions [PAL (n = 22) or reminiscing (n = 18)] twice/week for 12 weeks. PAL interventionist encourages residents to perform skills with the visiting dog; reminiscing interventionist encourages residents to reminisce. Monthly assessment of physical (energy expenditure, activities of daily living), emotional (depression, apathy), and behavioral (agitation) function. RESULTS: In linear mixed models, physical activity depressive symptoms improved more with PAL. CONCLUSION: Evidence supports that the PAL program helps preserve/enhance function of AL residents with CI. Additional study is required to evaluate the duration and predictors of effectiveness of the PAL intervention. PMID- 25118335 TI - Oil binding capacities of triacylglycerol crystalline nanoplatelets: nanoscale models of tristearin solids in liquid triolein. AB - Polycrystalline particles composed of triacylglycerol (TAG) molecules, and their networks, in anhydrous TAG oils find extensive use as edible oils in the food industry. Although modelling studies of TAG systems, have been carried out, none have attempted to address a problem of central concern to food science and technology: the "oil binding capacity" of a system of such edible oils. Crystalline nanoparticles (CNPs) have recently been identified as the fundamental components of solid fats in oils. Oil binding capacity is an important concept regarding the ability of fats particles to retain oil, and the ability of these CNPs to bind oil is important in designing healthy foods. We have carried out atomic scale molecular dynamics computer simulations to understand the behavior of a triacylglycerol oil (triolein) in nanoscale confinements between tristearin CNPs. We define a nanoscale oil binding capacity function by utilizing the average oil number density, , between two CNPs as a function of their separation, d. We modelled pure tristearin CNPs as well as tristearin CNPs in which the surfaces are covered with an interface comprising soft permanent coatings. Their surfaces are "hard" and "soft" respectively. We found that for a pair of hard-surface tristearin CNPs a distance d apart, (i) triolein exhibits number density, and therefore density, oscillations as a function of d, and (ii) the average number density between two such CNPs decreases as d decreases, viz. the oil binding capacity is lowered. When a soft layer of oil covers the CNP surfaces, we found that the oscillations are smeared out and that the average number density between the two CNPs remained approximately constant as d decreased indicating a high oil binding capacity. Our results might have identified important nanoscale aspects to aid in healthy food design. PMID- 25118334 TI - Strengthening the dementia care triad: identifying knowledge gaps and linking to resources. AB - This article describes a project to identify the needs of family caregivers and health care providers caring for persons with dementia. Participants included 128 caregivers, who completed a survey, and 27 health care providers, who participated in a focus group and completed a survey. Caregivers reported their primary source of information about the disease was the doctor; however, the majority also reported they were primarily informed of medications and not about needed resources. Health care providers identified limited time with patients and families, and lack of awareness of community services, as their main challenges. Recommendations include strengthening the partnership between physicians, patients, and caregivers (the dementia care triad) through additional support and training for physicians and caregivers, increasing awareness of the Alzheimer's Association, and utilization of technology for families and professionals to track the needs of persons with dementia. PMID- 25118336 TI - Direct analysis of quaternary alkaloids by in situ reactive desorption corona beam ionization MS. AB - The direct detection of quaternary alkaloids by atmospheric pressure chemical ionization (APCI)-base ambient MS is difficult because of their poor volatility. In this study, a reactive protocol was developed for the in situ determination of quaternary alkaloids using desorption corona beam ionization (DCBI) mass spectrometry (MS). The model compounds of 8 quaternary alkaloids including sanguinarine, chelerythrine, cyclanoline, nitidine, coptisine, jatrorrhizine, berberine, palmatine and 2 tertiary alkaloids including protopine and allocryptopine were investigated in different states such as on a polytetrafluoroethylene (PTFE) plate, in raw herbal materials, and in silica gel. After various reactive reagents were studied, the mixture of saturated aqueous NaOH solution and CH3OH solvent (3 : 7, v/v) was selected as the optimized reactive reagent for the reactive DCBI-MS detection. All the target molecules can be detected with high sensitivity. On a PTFE plate the limits of detection were 0.0795, 0.1060, 0.4860, 0.9665, 0.8879, 0.3987, 0.5557, 0.4591, 0.0889, and 0.1929 mg L(-1) for sanguinarine, chelerythrine, cyclanoline, nitidine, coptisine, jatrorrhizine, berberine, palmatine, protopine, and allocryptopine, respectively. The reactive protocol was also applied to the direct detection of raw herbal materials and thin layer chromatography successfully. PMID- 25118338 TI - Near infrared hyperspectral imaging for forensic analysis of document forgery. AB - Hyperspectral images in the near infrared range (HSI-NIR) were evaluated as a nondestructive method to detect fraud in documents. Three different types of typical forgeries were simulated by (a) obliterating text, (b) adding text and (c) approaching the crossing lines problem. The simulated samples were imaged in the range of 928-2524 nm with spectral and spatial resolutions of 6.3 nm and 10 MUm, respectively. After data pre-processing, different chemometric techniques were evaluated for each type of forgery. Principal component analysis (PCA) was performed to elucidate the first two types of adulteration, (a) and (b). Moreover, Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) was used in an attempt to improve the results of the type (a) obliteration and type (b) adding text problems. Finally, MCR-ALS and Partial Least Squares-Discriminant Analysis (PLS-DA), employed as a variable selection tool, were used to study the type (c) forgeries, i.e. crossing lines problem. Type (a) forgeries (obliterating text) were successfully identified in 43% of the samples using both the chemometric methods (PCA and MCR-ALS). Type (b) forgeries (adding text) were successfully identified in 82% of the samples using both the methods (PCA and MCR ALS). Finally, type (c) forgeries (crossing lines) were successfully identified in 85% of the samples. The results demonstrate the potential of HSI-NIR associated with chemometric tools to support document forgery identification. PMID- 25118337 TI - Highly sensitive and selective detection of Pb2+ ions using a novel and simple DNAzyme-based quartz crystal microbalance with dissipation biosensor. AB - A novel, label-free DNAzyme-based quartz crystal microbalance with dissipation monitoring (QCM-D) biosensor was developed for the highly sensitive and specific detection of Pb(2+) ions. To enhance the performance of the sensor, oligonucleotide-functionalized gold nanoparticles were used for both frequency and dissipation amplification. This sensor was developed by immobilizing Pb(2+) specific DNAzymes onto the QCM-D sensor surface and allowing them to hybridize with substrate-functionalized AuNPs. The DNAzyme catalyzed the cleavage of the substrate in the presence of Pb(2+) ions, causing the cleaved substrate functionalized AuNPs to be removed from the sensor surface. Thus, Pb(2+) ions can be determined on-line by monitoring the change in frequency and dissipation signals. The results revealed that the sensor showed a sensitive response to Pb(2+) ions with detection limits of 14 nM and 20 nM for frequency and dissipation, respectively. This QCM-D biosensor also exhibited excellent selectivity toward Pb(2+) ions in the presence of other divalent metal ions. In addition, the approach was able to detect Pb(2+) in tap water, demonstrating its great potential for monitoring drinking water quality. The proposed sensor system described here represents a new class of lead ion sensor. Its simple detection strategy makes it feasible for 'pollution-free' detection; thus, the approach could have applications in on-line water quality monitoring. PMID- 25118339 TI - Nanopipette delivery: influence of surface charge. AB - In this report, transport through a nanopipette is studied and the interplay between current rectification and ion delivery for small pipettes is examined. First, surface charge dependence of concentration polarization effects in a quartz nanopipette was investigated. Electrical characterization was performed through current-potential (I-V) measurements. In addition, fluorescein (an anionic fluorescent probe) was utilized to optically map ion enrichment and ion depletion in the nanopipette tip. Bare nanopipettes and polyethylenimine (PEI) modified nanopipettes were examined. Results confirm that concentration polarization is a surface charge dependent phenomenon and delivery can be controlled through modification of surface charge. The relationship between concentration polarization effects and voltage-driven delivery of charged electroactive species was investigated with a carbon ring/nanopore electrode fabricated from pyrolyzed parylene C (PPC). Factors such as surface charge polarity of the nanopipette, electrolyte pH, and electrolyte concentration were investigated. Results indicate that with modification of surface charge, additional control over delivery of charged species can be achieved. PMID- 25118340 TI - Dual amplification of single nucleotide polymorphism detection using graphene oxide and nanoporous gold electrode platform. AB - In the present manuscript, a strategy to prompt the sensitivity of a biosensor based on the dual amplification of signal by applying a nanoporous gold electrode (NPGE) as a support platform and soluble graphene oxide (GO) as an indicator has been developed. By increasing the surface area of the biosensing platform and because of unique GO/ss-DNA interactions, the sensitivity for the detection of SNPs is enhanced. In the presence of SNPs, because of less effective hybridization of mutant targets compared to complementary targets, further GO could adsorb on mutant targets-modified NPGE viapi-pi interactions, causing a large increase in the charge transfer resistance (Rct) of the electrode. This protocol provides a cost-effective and fast method for the discrimination of different SNPs. Furthermore, this biosensor can detect thermodynamically stable SNP (G-T mismatches) in the range of 15-1600 pM. The present strategy is a label free and sensitive protocol and does not require sophisticated fabrication. PMID- 25118341 TI - Electrolytic valving isolation of cell co-culture microenvironment with controlled cell pairing ratios. AB - Cancer-stromal interaction is a critical process in tumorigenesis. Conventional dish-based co-culture assays simply mix two cell types in the same dish; thus, they are deficient in controlling cell locations and precisely tracking single cell behavior from heterogeneous cell populations. Microfluidic technology can provide a good spatial-temporal control of microenvironments, but the control has been typically realized by using external pumps, making long-term cultures cumbersome and bulky. In this work, we have presented a cell-cell interaction microfluidic platform that can accurately control the co-culture microenvironment by using a novel electrolytic cell isolation scheme without using any valves or pneumatic pumps. The proposed microfluidic platform can also precisely control the number of interacting cells and pairing ratios to emulate cancer niches. More than 80% of the chambers captured the desired number of cells. The duration of cell isolation can be adjusted by electrolytic bubble generation and removal. We have verified that the electrolytic process has a negligible effect on cell viability and proliferation in our platform. To the best of our knowledge, this work is the first attempt to incorporate electrolytic bubble generation as a cell isolation method in microfluidics. For proof of feasibility, we have performed cell-cell interaction assays between prostate cancer (PC3) cells and myoblast (C2C12) cells. The preliminary results demonstrated the potential of using electrolysis for micro-environmental control during cell culture. Also, the ratio controlled cell-cell interaction assays were successfully performed which showed that the cell pairing ratios of PC3 to C2C12 affected the proliferation rate of myoblast cells due to increased secretion of growth factors from prostate cancer cells. PMID- 25118343 TI - Development and delivery of a high-quality European Cardiovascular Magnetic Resonance Examination. PMID- 25118342 TI - Authors' response. PMID- 25118344 TI - The Glasgow Cardiovascular Research Centre of the British Heart Foundation. PMID- 25118345 TI - Country of the month: Ireland 2014. PMID- 25118346 TI - Automated external defibrillators should be mandatory on board all commercial airliners. PMID- 25118347 TI - Author's response. PMID- 25118348 TI - High-dimensional cytometry. Preface. PMID- 25118349 TI - Retracted: Synthesis and cytotoxic activity of 2-anilinopyridine-3-acrylamides as tubulin polymerization inhibitors. PMID- 25118350 TI - How to become a successful researcher: tips for early career researchers. PMID- 25118351 TI - Elucidation of sevadicin, a novel non-ribosomal peptide secondary metabolite produced by the honey bee pathogenic bacterium Paenibacillus larvae. AB - American foulbrood (AFB) caused by the bee pathogenic bacterium Paenibacillus larvae is the most devastating bacterial disease of honey bees worldwide. From AFB-dead larvae, pure cultures of P. larvae can normally be cultivated indicating that P. larvae is able to defend its niche against all other bacteria present. Recently, comparative genome analysis within the species P. larvae suggested the presence of gene clusters coding for multi-enzyme complexes, such as non ribosomal peptide synthetases (NRPSs). The products of these enzyme complexes are known to have a wide range of biological activities including antibacterial activities. We here present our results on antibacterial activity exhibited by vegetative P. larvae and the identification and analysis of a novel antibacterially active P. larvae tripeptide (called sevadicin; Sev) produced by a NRPS encoded by a gene cluster found in the genome of P. larvae. Identification of Sev was ultimately achieved by comparing the secretome of wild-type P. larvae with knockout mutants of P. larvae lacking production of Sev. Subsequent mass spectrometric studies, enantiomer analytics and chemical synthesis revealed the sequence and configuration of the tripeptide, D-Phe-D-ALa-Trp, which was shown to have antibacterial activity. The relevance of our findings is discussed in respect to host-pathogen interactions. PMID- 25118352 TI - Cyclic-di-GMP levels affect Pseudomonas aeruginosa fitness in the presence of imipenem. AB - A large number of genes coding for enzymes predicted to synthesize and degrade 3' 5-cyclic diguanylic acid (c-di-GMP) is found in most bacterial genomes and this dinucleotide emerged as an intracellular signal-controlling bacterial behaviour. An association between high levels of c-di-GMP and antibiotic resistance may be expected because c-di-GMP regulates biofilm formation and this mode of growth leads to enhanced antibiotic resistance. However, a clear understanding of this correlation has not been established. We found that increased levels of c-di-GMP in Pseudomonas aeruginosa improve fitness in the presence of imipenem, even when grown as planktonic cells. P. aeruginosa post-transcriptionally regulates the amounts of five porins in response to c-di-GMP, including OprD, responsible for imipenem uptake. Cells with low c-di-GMP levels are consequently more sensitive to this antibiotic. Main efflux pumps or beta-lactamase genes did not show altered mRNA levels in P. aeruginosa strains with modified different c-di-GMP concentrations. Together, our findings show that c-di-GMP levels modulate fitness of planktonic cultures in the presence of imipenem. PMID- 25118353 TI - Efficacy of scorpion antivenom in children--author's reply. PMID- 25118354 TI - Experience of nutrition rehabilitation centers in management of SAM--author's reply. PMID- 25118355 TI - Cord blood TSH for screening of hypothyroidism: is it justified--author's reply. PMID- 25118356 TI - Good night, sleep tight. Get better sleep without taking a pill. PMID- 25118357 TI - The best options for different types of neck pain. Prompt treatment can help prevent long-term problems. PMID- 25118358 TI - Finding relief for recalcitrant bursitis pain. PMID- 25118359 TI - Improving range of motion in arthritic joints. PMID- 25118360 TI - What to do about back spasms. PMID- 25118361 TI - Is it safe to use nonprescription topical medication for my joint and muscle pain? PMID- 25118362 TI - I have knee osteoarthritis (OA), and a friend recommended shock-absorbing insoles to reduce the pain. Are they really effective? PMID- 25118363 TI - Back pain and bedtime--getting the right support. PMID- 25118364 TI - Lowering your breast cancer risk. A daily pill can hold the key to prevention for some women. PMID- 25118365 TI - Pain of a higher order: cluster headaches. PMID- 25118366 TI - [Clinical oncology and the status of oncosurgery]. PMID- 25118368 TI - Medical devices; gastroenterology-urology devices; classification of the implantable transprostatic tissue retractor system. Final order. AB - The Food and Drug Administration (FDA) is classifying the implantable transprostatic tissue retractor system into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID- 25118367 TI - Gastroenterology-urology devices; reclassification of implanted blood access devices. Final rule. AB - The Food and Drug Administration (FDA) is issuing a final order to reclassify implanted blood access devices, a preamendments class III device, into class II (special controls) based on new information and subject to premarket notification and to further clarify the identification. PMID- 25118369 TI - Final priority; National Institute on Disability and Rehabilitation Research- Disability and Rehabilitation Research Projects and Centers Program. Final priority. AB - The Assistant Secretary for Special Education and Rehabilitative Services announces a priority under the Disability and Rehabilitation Research Projects and Centers Program administered by the National Institute on Disability and Rehabilitation Research (NIDRR). Specifically, we announce a priority for a Disability and Rehabilitation Research Project (DRRP) on Improving Methods of Evaluating Return on Investment (ROI) for the State Vocational Rehabilitation Services Program (VR Program). The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2014 and later years. We take this action to focus research attention on an area of national need. We intend for the priority to contribute to improved employment outcomes for individuals with disabilities. PMID- 25118370 TI - Final priority; National Institute on Disability and Rehabilitation Research- Rehabilitation Research and Training Centers. Final priority. AB - The Assistant Secretary for Special Education and Rehabilitative Services announces a priority for the Rehabilitation Research and Training Center (RRTC) Program administered by the National Institute on Disability and Rehabilitation Research (NIDRR). Specifically, we announce a priority for an RRTC on Vocational Rehabilitation Practices for Youth and Young Adults. The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2014 and later years. We take this action to focus research attention on an area of national need. We intend for this priority to contribute to improved outcomes for youth and young adults with disabilities in the State Vocational Rehabilitation Services program. PMID- 25118371 TI - Final priority; National Institute on Disability and Rehabilitation Research- Research Fellowships Program (also known as the Mary E. Switzer Research Fellowships). Final priority. AB - The Assistant Secretary for Special Education and Rehabilitative Services announces a priority for the Research Fellowships Program administered by the National Institute on Disability and Rehabilitation Research (NIDRR). Specifically, this notice announces a priority for a Distinguished Residential Disability and Rehabilitation Policy Fellowship. We take this action to focus attention on an area of national need. We intend the priority to build research capacity by providing support to highly qualified, experienced researchers, including those who are individuals with disabilities, to conduct policy research in the areas of disability and rehabilitation. PMID- 25118372 TI - Rules regarding the health insurance premium tax credit. Final and temporary regulations. AB - This document contains final and temporary regulations relating to the health insurance premium tax credit enacted by the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010, as amended by the Medicare and Medicaid Extenders Act of 2010, the Comprehensive 1099 Taxpayer Protection and Repayment of Exchange Subsidy Overpayments Act of 2011, and the Department of Defense and Full-Year Continuing Appropriations Act of 2011 and the 3% Withholding Repeal and Job Creation Act. These regulations affect individuals who enroll in qualified health plans through Affordable Insurance Exchanges (Exchanges) and claim the premium tax credit, and Exchanges that make qualified health plans available to individuals. The text of the temporary regulations in this document also serves as the text of proposed regulations set forth in a notice of proposed rulemaking (REG-104579-13) on this subject in the Proposed Rules section in this issue of the Federal Register. PMID- 25118373 TI - Branded prescription drug fee. Final regulations, temporary regulations, and removal of temporary regulations. AB - This document contains final regulations that provide guidance on the annual fee imposed on covered entities engaged in the business of manufacturing or importing branded prescription drugs. This fee was enacted by section 9008 of the Patient Protection and Affordable Care Act, as amended by section 1404 of the Health Care and Education Reconciliation Act of 2010. This document also withdraws the Branded Prescription Drug Fee temporary regulations and contains new temporary regulations regarding the definition of controlled group that apply beginning on January 1, 2015. The final regulations and the new temporary regulations affect persons engaged in the business of manufacturing or importing certain branded prescription drugs. The text of the temporary regulations in this document also serves as the text of proposed regulations set forth in a notice of proposed rulemaking (REG-123286-14) on this subject in the Proposed Rules section in this issue of the Federal Register. PMID- 25118374 TI - [Study on adjuvant effect of oral recombinant subunit vaccine formulated with chitosan against human enterovirus 71]. AB - To evaluate the adjuvant effect of recombinant enterovirus 71 (EV71) subunit vaccine formulated with chitosan, rabbits were orally immunized with recombinant VP1 (rVP1) or rVP1 mixed with chitosan adjuvant. Levels of virus-specific IgG and IgA antibodies in sera, mucosal wash buffer (intestine, nasal cavity, and lung), and feces were determined by indirect enzyme-linked immunosorbent assay (ELISA). The titers of neutralizing antibodies against EV71 were determined using cytopathic effect-based neutralizing assay, and levels of cytokines (IFN-gamma and IL-4) secreted from in vitro-cultured rabbit splenic lymphocytes under antigen stimulation were also determined by ELISA. Results showed that immunization with rVP1 alone could only induce low levels of serum IgG and mucosal IgA, while rVP1 combined with chitosan adjuvant were able to induce significantly higher levels of antibodies, rVP1 can only induce neutralizing antibodies when used in combination with chitosan. Levels of IFN-gamma and IL-4 in the group immunized with rVP1 plus chitosan were significantly higher than those in the group immunized with rVP1 only or those in the control groups. Our study lays the foundation for development of oral VP1 vaccine against EV71 infection. PMID- 25118376 TI - [Severe fever with thrombocytopenia syndrome virus nucleoprotein specifically binds to 60kD SSA/Ro protein in host cells]. AB - This study aims to investigate whether the nucleoprotein (NP) of severe fever with thrombocytopenia syndrome virus (SFTSV) can impact the cellular immunity of host cells. Gene segments that encode the NP and non-structural protein (NSs) of SFTSV were inserted into eukaryotic expression vector VR1012. Host proteins that interact with NP and affect immunity were identified with co-immunoprecipitation (IP), SDS-PAGE, mass spectrometry (MS), and Western blot. Co-localization of NP and the identified host proteins was confirmed by confocal microscopy. A 60kD SSA/Ro, a protein related to immunity, interacted with NP, as found by IP and MS. Confocal microscopy showed that NP and SSA/Ro were co-localized in cytoplasm. These results indicated that SFTSV NP may specifically bind to 60kD SSA/Ro and cause a series of immune responses and clinical symptoms. PMID- 25118375 TI - [Immunoprotective effect of inactivated coxsackievirus A16 vaccine in mice]. AB - This study aims to construct inactivated coxsackievirus A16 (CVA16) vaccine and to investigate its protective effect in ICR mice. A clinical isolate of CVA16, 521-01T, was cultured in VERO cells, inactivated by formaldehyde, and purified by ultracentrifugation for vaccine preparation. Purity and other characteristics of the vaccine were determined by SDS-PAGE and Western blot. Female ICR mice were subcutaneously inoculated with inactivated CVA16 or Al(OH)3-absorbed CVA16, followed by booster immunization at the end of 2 and 4 weeks. CVA16-specific IgG titers in serum were determined by ELISA, and titers of neutralizing antibodies were determined by viral neutralization assay. The immunity of T lymphocytes was evaluated by IFN-gamma ELISPOT assay. The protective effect was evaluated by challenging the neonatal offspring (< 48 hours) of vaccinated female mice with 1 000 LD50 of CVA16 521-01T. The mortality rates of different groups were compared. The results showed that Al(OH)3 +CVA16 could induce high titers of specific IgG antibodies in ICR mice. After being boosted two times, the serum IgG antibody titer could reach up to 1 : 1 x 10(5) (P = 0.000), and neutralizing antibody titer was higher than 1 : 256. Additionally, more spot forming cells were induced in the immunized groups than in the negative controls. The maternal antibodies showed protective effect in 100% of the neonatal mice challenged with 1 000 LD50 of CVA16 521-01T. The inactivated CVA16 vaccine has ideal immunogenicity and immunoprotective effect. This research lays a foundation for the development and evaluation of CVA16 vaccines. PMID- 25118377 TI - [Virological impact of stalk region of neuraminidase in influenza A/Anhui/1/05 (H5N1) and A/Ohio/07/2009 (H1N1) viruses]. AB - This study aims to investigate the virological impact of the stalk region and cysteine (C) in neuraminidase (NA) of influenza A/Anhui/1/05 (H5N1) and A/Ohio/07/2009 (H1N1) viruses. The NA of A/ Anhui/1/05 (H5N1), defined as AH N1, lacked 20 amino acids (including C, defined as s20) as compared with NA of A/Ohio/07/2009 (H1N1) (defined as 09N1). We deleted s20 of 09N1 to construct 09N1 s20, and inserted s20 into AH N1 to construct AH N1+s20. To investigate the impact of C on the biological function of NA, we deleted C in 09N1 to construct 09N1-C and inserted C into AH N1 to construct AH N1-C. The pseudo-type viral particle (pp) system was used to evaluate the impact of these mutants on virology. The combination of 09N1-C and 09H1 (defined as 09H1::09N1-C) showed an infectivity 8 times that of the wild type 09H1::09N1, while the infectivity of the combination of AH N1+C and AH H5 (defined as AH H5::AH N1+C) was much lower than that of the wild type AH H5::AH N1. The infectivity of the combination of 09N1-s20 and 09H1 (defined as 09H1::09N1-s20) was 4 times that of the wild type 09H1::09N1; the infectivity of the combination of AH N1+s20 and AH H5 (defined as AH H5:: AH N1+s20) was 1/7 that of the wild type AH H5::AH N1. The co-existence of 09N1-C and AH H5 displayed 6 times the infectivity of AH H5::09N1, while the infectivity of 09H1::AH N1+C was very low. Multimer analysis showed that in the wild type 09N1, the forms of NA were dimer >> tetramer > monomer; the major component of NA in 09N1-C was monomer; in 09N1-s20, the forms of NA were monomer >> dimer. AH N1 was mainly composed of monomer; in AH N1+s20, the forms of NA were dimer >> monomer > tetramer; in AH N1+C, the forms of NA were dimer >> tetramer. Deletion of C or s20 from 09N1 did not change the expression of NA. The study suggested that deletion of C from the stalk region of NA in A/Ohio/07/2009 (H1N1) increases infectivity. Insertion of C into NA's stalk region of A/ Anhui/1/05 (H5N1) significantly decreases infectivity. Cysteine deletion in the stalk region is important for the infectivity of A/Anhui/1/05 (H5N1) and A/Ohio/07/2009 (H1N1). It may interfere with the infectivity via changes in NA polymerization. PMID- 25118378 TI - [Epidemiology of hand, foot, and mouth disease and genetic characterization of enterovirus A71: a survey from 2007 to 2012 in Linyi of Shandong Province, China]. AB - To investigate the epidemiology of hand, foot, and mouth disease (HFMD) and the genetic characteristics of enterovirus A71 (EV-A71) in Linyi of Shandong Province, China during 2007-2012. The number of reported HFMD cases were obtained from the National Notifiable Disease Reporting System (NNDRS) were analyzed by descriptive epidemiology method; the VP1 region of EV-A71 isolated from HFMD patients in Linyi was amplified and sequenced. Finally, the genetic variability and phylogenecity of VP1 sequences of EV-A71 were analyzed by MEGA 5.0. The results showed that HFMD incidence was reported in each year from 2007 to 2012 in Linyi, and the highest incidence and mortality were reported in 2009, when there were total 14697 cases and 9 of death. The reported incidence was 140.28/100000, and the mortality was 0.086/100000. The peak incidence usually occurred between April and July, and the summit occurred in May. Scattered children accounted for 77.37%-92.00% of all cases. The peak age was 2.5 years during 2007-2009 and 1.5 years during 2010-2012. A total of 1365 laboratory-confirmed HFMD cases were reported in the 6 consecutive years, accounting for 2.98% of the gross number. Among these reports, the ratio of EV-A71 was 44.18%, and the ratio of coxsackievirus A16 (CVA16) was 46.59%. All EV-A71 strains isolated in Linyi during 2007-2012 belonged to the C4a evolutionary branch of C4 genotype. In conclusion, HFMD outbreaks occurred every year in Linyi during 2007-2012. Incidence varied significantly among different counties. The peak incidence in each year lasted from April to July. Most of the patients were children under 3 years of age, and scattered children took the highest proportion. Co-circulation of EV-A71 and CVA16 was the major cause of HFMD in each year. Since the first report of HFMD prevalence caused by EV-A71 (C4a) in 2007, the virus has been prevalent continuously in Linyi for 6 years. PMID- 25118379 TI - [Study on the B cell linear epitopes of rabies virus CVS-11 nucleoprotein]. AB - To study the B cell linear epitopes of rabies virus CVS-11 nucleoprotein, peptides were synthesized according to the amino acid sequences of B cell linear epitopes. Linear epitopes predicted by bioinformatics analysis were evaluated with immunological techniques. Indirect enzyme-linked immunosorbent assay showed that titers of antibodies to peptides (355-369 and 385-400 residues of rabies virus CVS-11 nucleoprotein) were above 1:12 800 in mouse sera. The antibodies recognized denatured rabies virus CVS-11 nucleoprotein in Western blot analysis. Purified anti-peptide antibodies recognized natural rabies virus CVS-11 nucleoprotein in BHK-21 cells in indirect fluorescent antibody test. The 355-369 and 385-400 residues of rabies virus CVS-11 nucleoprotein were validated as B cell linear epitopes. PMID- 25118380 TI - [Genome amplification and sequence analysis of human bocavirus 2]. AB - To obtain the genome sequence of human bocavirus 2 (HBoV2), different regions of HBoV2 genome were amplified through PCR in fecal specimens which had been identified as single-positive for HBoV2 in 2010. A genome sequence of HBoV2 (HBoV2-NC, 5444 bp) was obtained after sequence assembly. The phylogenetic analysis showed that HBoV2-NC had the closest evolutionary relationship with HBoV2 Lanzhou strain. The predication of inverted terminal repeats of HBoV2-NC by DINAMelt showed that inverted terminal repeats were contained in HBoV2-NC 5' terminal, which had the typical stem-loop structure in other parvoviruses. Finally, some flanking sequences of HBoV2-NC were amplified by linker-PCR. PMID- 25118381 TI - [Genetic characteristics of influenza A/H3N2 virus neuraminidase gene: a survey from 2010 to 2012 in Qinghai Province, China]. AB - This study aims to perform a survey of genetic variation in neuraminidase (NA) gene of influenza A/H3N2 virus, as well as related resistance to NA inhibitors, in Qinghai Province of China, 2010 to 2012. Strains of influenza A/H3N2 isolated during an influenza survey from 2010 to 2012 in Qinghai were enrolled by random sampling. Viral RNA was extracted and amplified by RT-PCR. Purified PCR products were sequenced thereafter. Genetic analysis of nucleic acid and the derived amino acid sequences was performed by MEGA 4.0. Phylogenetic trees were also constructed. Strains isolated during 2010-2011 in this study clustered closely with World Health Organization (WHO) 2010-2012 reference vaccine strain A/Perth/16/2009 and 2008-2010 reference vaccine strain A/Brisbane/10/2007 on the phylogenetic tree, while the 2012 isolates were located on another branch. In analysis of derived amino acid sequences, the 2010 isolates mutated at K81T, the 2011 isolates mutated at I26V and D127N, while the 2012 isolates mutated at E41K, P46A, I58V, T71N, L81P, D93G, D127N, D151N, and I307M. The D151N mutation added a glycosylation site to the activity center of NA. No significant variation was discovered in H3N2 NA gene of 2010-2011 isolates in Qinghai, China. Isolates of 2012 were found with significant mutation, which has the potential of inducing minor resistance to NA inhibitors like zanamivir and oseltamivir. PMID- 25118382 TI - [Research on construction of sheep lung adenomas virus pEGFP-C1/exJSRV-env and induction of malignant transformation in NIH3T3]. AB - This study aims to construct a eukaryotic expression system for envelope gene of Jaagsiekte sheep retrovirus, observes its localization in 293T cells, and investigates the potential in inducing malignant transformation of NIH3T3 cells. By RT-PCR, the full-length cDNA of envelope gene of Jaagsiekte sheep retrovirus (exJSRV-env) was amplified from the extract of naturally infected sheep lung. The clone of target gene was sub-cloned into eukaryotic expression system pEGFP-C1, and validated by PCR, restriction endonuclease, and sequencing. Bioinformatic analysis concerning biological function and cellular localiza tion of exJSRV-env was also performed. The recombinant clone of exJSRV-env was transfected into 293T cells and NIH3T3 cells by Lipofectamine LTX. The expression and celluar localization in 293T cells were validated by confocal microscopy. Soft agar colony formation assay was employed to test the anchorage-independent growth of NIH3T3. DNA sequencing and restriction enzyme digestion with Kpn I and Hind III indicated the correct construction of the recombinant plasmid, which was named pEGFP-C1/exJSRV-env. Amino acid sequence alignment of exJSRV-env with reference sequences found 85%-100% homogeneity. A YRNM motif was discovered at the cytoplasmic tail of envelope gene, which is exclusively found in exogenous viruses. Phylogenetic tree analysis showed that our clone of exJSRV-env clustered closely with pathogenic exogenous Jaagsiekte sheep retroviruses. Fluorescence microscopy indicated typical membrane localization of exJSRV-env protein. NIH3T3 cells transfected with exJSRV-env lost contact inhibition, and acquired colony forming ability in soft agar. This study indicated that envelope protein of Jaagsiekte sheep retrovirus can induce malignant transformation of mouse fibroblast cell NIH3T3. Discoveries of this study provide a basis for further structural and functional research on Jaagsiekte sheep retrovirus envelope protein. PMID- 25118383 TI - [Optimization of electroporation parameters for ctenopharyngodon idellus kidney cells and transient expression of grass carp reovirus NS26 protein]. AB - In this study, pEGFP-N1 was chosen as the reporter plasmid and transferred into Ctenopharyngodon idellus kidney (CIK) cells by electroporation, and the optimal electroporation conditions were determined by testing the transfection efficiency with different voltages, pulse times, plasmid amounts, and numbers of shocks. The results showed that the maximum electroporation efficiency was achieved under the following conditions in a 0.2 cm electroporation cuvette containing CIK cells (1.5 x 10(7)/mL, 200 microl): electric voltage 200 V, pulse time 45 ms, plasmid 30 microg, and one electric shock. The total genomic RNA of grass carp reovirus (GCRV) was extracted in this experiment and reversely transcribed into cDNA, which was used to amplify the gene segment of GCRV non-structural protein NS26 using designed specific primers. The PCR product was recombined into pEGFP-N1 vector. The fusion protein EGFP-NS26 was successfully and efficiently expressed in the CIK cells by electroporation, which was confirmed by both fluorescent imaging and Western blot analysis. This experiment laid a foundation for further functional studies of the non-structural protein NS26 of GCRV. PMID- 25118384 TI - [Effects of bm47 deletion on viral replication and transcription of Bombyx mori nucleopolyhedrovirus]. AB - Bombyx mori nucleopolyhedrovirus (BmNPV) bm47 gene is found in all sequenced lepidopteran nucleopolyhedroviruses (NPVs). It is one of the core genes of NPVs. However, the role of bm47 in the biological cycle of NPV remains unknown. In this study, the Red recombination system was used to knock out bm47 from BmNPV to construct bm47-ko-Bacmid in E. coli BW25113 system. Then bm47 gene was introduced back to the viral genome using the Bac-to-Bac system to create the repair virus bm47-re-Bacmid. TCID50 assay and real-time PCR (qPCR) were used to evaluate the effects of bm47 deletion on viral DNA replication, gene transcription, and protein expression. qPCR results showed that bm47 knock-out had no significant effect on viral DNA replication. However, the qPCR results showed that bm47-ko Bacmid significantly decreased the transcription levels of early gene lef-3, late gene vp39, and very late gene p10 at 48 h and 72 h after viral transfection of BmN cells (P < 0.05). This work will provide a foundation for further studies on the biological function of BmNPV bm47 in viral replication and transcription. PMID- 25118385 TI - [Characterization of Marburg virus morphology]. AB - Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae. Filoviruses cause severe filovirus hemorrhagic fever (FHF) in humans, with high case fatality rates, and represent potential agents for bioterrorism and biological weapons. It is necessary to keep surveillance of filoviruses, even though there is no report of their isolation and patients in China so far. To characterize MARV morphology, the Lake Victoria marburgvirus--Leiden was stained negatively and observed under a transmission electron microscope which is one of important detection methods for filoviruses in emergencies and bioterrorism. MARV showed pleomorphism, with filamentous, rod-shaped, cobra-like, spherical, and branch-shaped particles of uniform diameter but different lengths. Pleomorphism of negatively stained MARV is summarized in this article, so as to provide useful information for possible electron microscopic identification of filoviruses in China. PMID- 25118386 TI - [A review of detection methods for human bocaviruses]. AB - Human bocavirus (HBoV) 1-4 have been detected both in respiratory and stool samples since the first HBoV was discovered in 2005. HBoV-1 is mostly associated with respiratory infection, while HBoV 2-4 are usually associated with intestinal tract infection. A variety of signs and symptoms have been described in patients with HBoV infection, including cough, wheezing, pneumonia, and diarrhea, but the research on pathogenic mechanism of HBoV is limited because HBoV cannot be cultured in vitro due to the lack of appropriate host cells. Three-dimensional epithelial cell culture, reverse genetics, and viral metagenomics are identified as novel tools that may promote the research on pathogenic mechanism of HBoV and the discovery of new viruses. This review summaries currently available diagnostic approaches such as electron microscopy, cell culture, PCR, and immunoassay in order to provide a method reference for indepth research on HBoV. PMID- 25118387 TI - [Research progress in receptors involved in rotavirus infection]. AB - Rotaviruses, which are recognized as one of the major etiological agents among infants and young children with diarrhea, consist of three concentric layers of protein capsid with the enclosed double-stranded RNA genome. Rotaviruses infect host cells mainly by identifying the specific receptors on cell surfaces and binding to them. Therefore, receptors are important factors for viruses infecting cells. So far, there have been many receptors found to be involved in rotavirus infection, including sialic acid, integrin, Toll-like receptor, and blood group antigen. This article provides an overview of receptors involved in rotavirus infection. PMID- 25118388 TI - [An overview of surveillance of avian influenza viruses in wild birds]. AB - Wild birds (mainly Anseriformes and Charadriiformes) are recognized as the natural reservoir of avian influenza viruses (AIVs). The long-term surveillance of AIVs in wild birds has been conducted in North America and Europe since 1970s. More and more surveillance data revealed that all the HA and NA subtypes of AIVs were identified in the wild ducks, shorebirds, and gulls, and the AIVs circulating in wild birds were implicated in the outbreaks of AIVs in poultry and humans. Therefore, the AIVs in wild birds pose huge threat to poultry industry and human health. To gain a better understanding of the ecology and epidemiology of AIVs in wild birds, we summarize the transmission of AIVs between wild birds, poultry, and humans, the main results of surveillance of AIVs in wild birds worldwide and methods for surveillance, and the types of samples and detection methods for AIVs in wild birds, which would be vital for the effective control of avian influenza and response to possible influenza pandemic. PMID- 25118389 TI - [Advances in research on oncolytic adenoviruses in tumor therapy]. AB - Oncolytic adenoviruses (Ads), which are live, replication-competent viruses that can selectively replicate in tumor cells and lead to cell lysis, have been used in tumor therapy. But due to the complexity and high mutability of human tumors, it becomes a major strategy to improve the selectivity, efficacy, and safety of oncolytic Ads. The oncolytic Ads that can express short hairpin RNA, cytokines, suicide gene, and matrix-modulating proteins have higher antitumor activity than the wild type. Tumor-specific promoters, especially hTERT and HRE promoters, increase the selectivity of oncolytic Ads for tumor cells. Moreover, oncolytic Ads surface-modified by polyethylene glycol (PEG), liposomes, biodegradable nanoparticles, and polypeptides have reduced immunogenicity and hepatotoxicity and improved antitumor activity when systemically administered, and the selectivity of oncolytic Ads can be significantly increased when linking PEG to antibodies, small peptides, cytokines, and ligands. Therefore, engineered oncolytic Ads combining the advantages of viral and non-viral vectors, as well as immunotherapy, are a promising strategy for improving the efficacy of targeted virotherapy. PMID- 25118390 TI - [Research progress in functions of coronavirus accessory genes]. AB - In addition to the structural genes of the coronavirus genome, S, E, M, and N, there are several additional genes called "group-specific or accessory genes". Their gene products are designated as "accessory proteins", as reports to date make it clear that these proteins are not essential for virus replication in vitro. Nevertheless, many of these genes are still maintained in the virus genome under selective pressure, suggesting that they might play a very important role in the survival of the virus in the natural environment of the infected host. This review will summarize the research progress in the functions of coronavirus accessory genes. PMID- 25118391 TI - [Studies on neuronal tracing with pseudorabies virus]. AB - With its abilities of trans-synaptic tracing and self-replication and wide host range, pseudorabies virus (PRV) has been applied in the field of neuroanatomy since the 1970s. Four decades of PRV application have made many advances in researches on neuronal tracing with PRV. Mechanism studies focused on investigating infection of primary neurons and tracing direction in secondary neurons, while application studies focused on development of new pathological strains and innovation of tracing techniques. To date, the mechanism and application of viral tracing are not completely figured out yet. Integration of molecular biology technology will improve the efficiency in related researches. PMID- 25118392 TI - [Preface for special issue on biomass refinery (2014)]. AB - Biomass is the most abundant organic macromolecules in nature, which is expected to achieve the brilliant of biorefinery equivalent to petroleum refining. However, it is considered as the future industry to human due to the complicated composition and transformation processes. The traditional lignocellulose bio refining thoughts ignored the functional requirements of products, but spent a lot of energies to destruct macromolecule into small molecules, and then converted the small molecules into different products, which was high energy consumption and low atom economy. How to realize the biorefinery of lignocellulose is the key point and difficulty to achieve the biomass industry. An ideal biorefinery of lignocellulose should as far as possibly to obtain the maximum yield of each component, to maintain the integrity of the molecule, to optimize the utilization of raw materials and finally to realize the maximum value. Therefore, it requires the raw materials refining of lignocellosic biomass should be based on the relationship of structure, process transformation and related product characteristics. This special issue reports the latest advances in the fields of raw material refinery, refining technologies, conversion technologies of component. PMID- 25118393 TI - [Sumac (Rhus chinensis Mill) biomass refinery engineering]. AB - Sumac (Rhus chinensis Mill) is an abundant and widely distributed Chinese native plant. Sumac fruit contains low content of vegetable oil, as an atypical oil plants hardly being processed through traditional vegetable oil production technologies. Based on our own studies on the characteristics of sumac fruit and branches, we established a novel model of sumac biomass refinery, and constructed the sumac biomass refinery technology system and eco-industrial chain integration. Steam explosion was the key technology, and several components fractionation technologies were integrated in the sumac biomass refinery system. The fractionated components were converted into different products depending on their functional features. Eight products including sumac fruit oil, biodiesel, protein feed, flavonoids, unbleached facial tissue, phenolic resin, biomass briquette and biogas were produced in the refinery. The extracted sumac fruit oil by steam explosion pretreatment was applied for the new food resource of Ministry of Health, and the permit was approved. This research provides a new model for the development of atypical wild plant resources. PMID- 25118394 TI - [Effect of pretreatment on topochemical and ultrastructural changes of lignocellulose plant cell walls: a review]. AB - Deconstruction of lignocellulosic plant cell walls to fermentable sugars by biochemical means is impeded by several poorly understood ultrastructural and chemical barriers. Pretreatment is an essential step by altering the morphological and compositional characteristics of biomass to enhance the sugar release during enzymatic hydrolysis. Therefore, getting insight into this field is necessary to improve the conversion of biomass into biofuels. In this review, we highlight our recent understanding on the impact of various promising pretreatments on biomass, with emphasis on the topochemical and ultrastructural changes of plant cell walls that are related to the reduction of recalcitrance and the consequence of saccharification. It will lend support to the scientific research and development with respect to biomass conversion. PMID- 25118395 TI - [Application of process engineering to remove lignocellulose fermentation inhibitors]. AB - Fermentation inhibitors are toxic to cells, which is one of the bottlenecks for lignocellulose bio-refinery process. How to remove those inhibitors serves a key role in the bioconversion of lignocellulose. This article reviews the sources and the types of the inhibitors, especially the updated removal strategies including physical methods, chemical methods, biological methods and inhibitor-tolerant strain construction strategies. Based on these, we introduce a new bio-refinery model named "fractional conversion", which reduces the production of inhibitors at pretreatment stage, and a novel in situ detoxification method named "fermentation promoter exploitation technology". This review could provide new research ideas on the removal of fermentation inhibitors. PMID- 25118396 TI - [Progress in natural laccase mediators from lignocelluloses]. AB - Laccase is one of the most important oxidoreductase with industrialization potential. However, due to the high cost and catalytic toxicity of laccase synthetic mediator, the laccase-mediator-system still cannot achieve industrialization. Therefore, searching for high efficient, environment-friendly, and cheap natural mediator from small molecule precursors or intermediates and degradation products of lignin has been considered as a hot research topic. Therefore, we introduce the type and catalytic mechanism of laccase mediator, the composition and separation of natural laccase mediator from water washed solution of steam exploded straw, black liquor and lignocelluloses degradation products during the fermentation of white-rot fungi. We also provide the theoretical and technical direction for exploring of high reactive of laccase natural mediators and achieving the oriented high-value utilization of lignocellulose degradation products. PMID- 25118397 TI - [Degumming of kenaf fibers by combining steam explosion with ultrasonic treatment]. AB - Kenaf has a high content of gum that is difficult to remove. Traditional chemical degumming process causes serious environmental pollution. To solve the problem, we developed a new method to degum kenaf. We pretreated the kenaf with steam explosion followed by ultrasonic treatment. We chose the single factor tests to select the ultrasonic frequency, sodium hydroxide concentration and processing time. Combined with orthogonal tests, we found that the optimum conditions were as follows: ultrasonic frequency was 28 kHz, sodium hydroxide concentration was 2%, and processing time was 60 min. Under these conditions, the residual gum of kenaf fiber was 9.72% and the fineness was 139.45 N(m). Steam explosion combined with ultrasonic method is effective in degumming of kenaf. PMID- 25118398 TI - [Low temperature plasma technology for biomass refinery]. AB - Biorefinery that utilizes renewable biomass for production of fuels, chemicals and bio-materials has become more and more important in chemical industry. Recently, steam explosion technology, acid and alkali treatment are the main biorefinery treatment technologies. Meanwhile, low temperature plasma technology has attracted extensive attention in biomass refining process due to its unique chemical activity and high energy. We systemically summarize the research progress of low temperature plasma technology for pretreatment, sugar platflow, selective modification, liquefaction and gasification in biomass refinery. Moreover, the mechanism of low temperature plasma in biorefinery and its further development were also discussed. PMID- 25118399 TI - [Effect of byproducts in lignocellulose hydrolysates on ethanol fermentation by Issatchenkia orientalis]. AB - Byproducts in lignocellulose hydrolysates, namely sodium formate (1 to 5 g/L), sodium acetic (2.5 to 8.0 g/L), furfural (0.2-2 g/L), 5-hydroxymethylfurfural (5 HMF, 1 to 1.0 g/L) or vanillin (0.5 to 2 g/L) were used to evaluate their effects on ethanol fermentation by Issatchenkia orientalis HN-1 using single factor test and the response surface central composite experiment. Results showed that most of the byproducts had no obvious inhibition on the production of ethanol, except for the addition of 2 g/L vanillin or 1 g/L of 5-HMF, which reduced the ethanol production by 20.38% and 11.2%, respectively. However, high concentration of some byproducts in lignocellulose hydrolysates, such as sodium formate (1 to 5 g/L), sodium acetic (2.5 to 8.0 g/L), furfural (0.2 to 2 g/L) and vanillin (0.5 to 2 g/L) inhibited the growth of I. orientalis HN-1 significantly. Compared with the control, the dry cell weight of I. orientalis HN-1 decreased by 25.04% to 37.02%, 28.83% to 43.82%, 20.06% to 37.60% and 26.39% to 52.64%, respectively, when the above components were added into the fermentation broth and the fermentation lasted for 36 h. No significant interaction effect of the various inhibitors (sodium formate, sodium acetic, furfural and vanillin) except for vanillin single factor on the ethanol production was observed based on the central composite experiments. The concentrations of byproducts in most lignocellulose hydrolysates were below the initial inhibition concentration on ethanol production by Issatchenkia orientalis HN-1, which indicated that Issatchenkia orientalis HN-1 can be used for ethanol production from lignocellulose hydrolysates. PMID- 25118400 TI - [Pretreatment of industrial lignin and catalytic conversion into phenol]. AB - Recent concerns about the gradual depletion of conventional fossil resources and the pressure from global climate change have accentuated the need for new alternative feedstock. As one of the main components in biomass, lignin is the second most abundant natural polymer after cellulose, and has the potential to serve as a sustainable source of energy and organic carbon to replace petroleum based chemicals. Efficient conversion of lignin into high value-added chemicals is crucial to improve the economic feasibility of biomass refinery. In the present study, several pretreatment technologies on industrial lignin were carried out to enhance phenol production. A microwave irradiation assisted biphasic reaction system was used to convert pretreated industrial lignin into phenolic compounds. Lignin conversion, reaction temperature, time and pretreatment method, were optimized. The highest phenol yield was 8.14% obtained from lignin pretreated by 1-ethyl-3-methylimidazolium acetate at 400 W for 60 min in a biophasic system catalyze by 1-aminoethyl-3-methylimidazolium tetrafluoroborate. PMID- 25118401 TI - [Pretreatment of ramie and kenaf stalk for bioethanol production]. AB - Ramie and kenaf were traditional fiber crops in China, but their stalk after decorticating has not been used effectively. The stalk contains a lot of cellulose, and can therefore be used for the production of bioethanol. We studied the effects of different chemical pretreatment on enzymatic digestibility of ramie stalk and kenaf stalk. Ramie and kenaf stalks pretreated with alkali were chosen to produce ethanol using quasi-simultaneous saccharification and fermentation (Q-SSF) process. The results show that for the stalks pretreated with 4% NaOH and 0.02% anthraquinone-2-sulfonic acid sodium salt (AQSS) as catalyzer at 170 degrees C for 1 h, the ethanol concentration could reach 51 g/L after fermentation for 168 h at 18% of solid substrate concentration. By fed batch to 20% of solid substrate concentration, the ethanol concentration could reach 63 g/L, 77% and 79% of the cellulose conversion could get for ramie stalk and kenaf stalk, respectively. For kenaf stalk pretreated with 5.2% NaHSO3 and 0.2% H2SO4 at 170 degrees C for 1 h, the ethanol concentration and cellulose conversion could reach to 65 g/L and 72%, respectively. PMID- 25118402 TI - [Effect of non-ionic surfactants on butanol production with Clostridium acetobutylicum ATCC 824]. AB - The low butanol concentration of acetone-butanol-ethanol fermentation causes uneconomical product recovery. In this work, the effect of small molecule non ionic surfactants on butanol fermentation was evaluated, using laboratory stocks of Clostridium acetobutylicum ATCC 824. Non-ionic surfactants substantially increased butanol production when additive amount was higher than 1% (W/W). Butanol concentration reached 16.9 g/L with 5% (W/W) Tween 80 and 100 g/L glucose in a 5 L fermenter. It was found that surfactants micelle solubilization capacity to butanol was very limited, indicating that butanol could hardly enter the surfactants micelle. Butanol production improvement was probably caused by cell surface hydrophobicity change due to surfactants adsorption. PMID- 25118403 TI - A new species and species-group of Simulium (Simulium) (Diptera: Simuliidae) from Thailand. AB - Simulium (Simulium) atipornae sp. nov. is described from females, males, pupae, and larvae in Thailand. This new species is characterized in the female by the claw with a small subbasal tooth, ovipositor valve triangular with its inner margin nearly straight; in the male by the style with a short subbasal protuberance and ventral plate Y-shaped, with toothed posterior margin; and in the pupa by the head and thoracic integument almost bare and gill with six filaments. Taxonomic notes are given to compare this new species with nine related species. A new species-group, the christophersi species-group, is proposed to accommodate S. atipornae sp. nov. and nine related species. PMID- 25118404 TI - Environmental factors related to the abundance and activity of Ochlerotatus albifasciatus (Diptera: Culicidae) in an agricultural landscape of steppe arid climate. AB - Ochlerotatus albifasciatus (Macquart) is a flood water mosquito whose highest density has been found associated both with natural landscapes (prairies or grazing fields) in temperate and subtropical regions and with rainfall events. In the current study, we aimed to find out how the marked differences between environmental factors of agricultural landscape patches in a steppe arid region affect the relative abundance of this species. In wetland patches, the high activity of adults was closely associated with the flood irrigation system, suggesting that the agricultural activity contributes to the proliferation of this mosquito. The steppe patches would constitute an adverse environment reflected by the abrupt decrease in abundance. Multiple linear regression showed that some explanatory variables, such as wetland patches and moment of the day (midday), did not contribute significantly to the relative abundance variation. In contrast, temperature, wind, and cloud cover seemed to regulate the biting activity of females. Temperature affected the activity of mosquitoes in the steppe but seemed to have no effect in wetland patches, where the activity of mosquitoes was permanent and more stable against changes in temperature. In the steppe, which presents low levels of humidity, scarce vegetation, and greater wind exposure, the activity seemed to be unstable against small thermal variations. The variability of the relative abundance of Oc. albifasciatus in an agricultural landscape was widely explained by temperature in combination with the microenvironment type, wind speed, and cloud cover and indirectly by human activity. PMID- 25118405 TI - Intra-annual changes in abundance of Aedes (Stegomyia) aegypti and Aedes (Ochlerotatus) epactius (Diptera: Culicidae) in high-elevation communities in Mexico. AB - We examined temporal changes in the abundance of the mosquitoes Aedes (Stegomyia) aegypti (L.) and Aedes (Ochlerotatus) epactius Dyar & Knab from June to October 2012 in one reference community at lower elevation (Rio Blanco; approximately 1,270 m) and three high-elevation communities (Acultzingo, Maltrata, and Puebla City; 1,670-2,150 m) in Veracruz and Puebla States, Mexico. The combination of surveys for pupae in water-filled containers and trapping of adults, using BG Sentinel traps baited with the BG-Lure, corroborated previous data from 2011 showing that Ae. aegypti is present at low abundance up to 2,150 m in this part of Mexico. Data for Ae. aegypti adults captured through repeated trapping in fixed sites in Acultzingo--the highest elevation community (approximately 1,670 m) from which the temporal intra-annual abundance pattern for Ae. aegypti has been described--showed a gradual increase from low numbers in June to a peak occurrence in late August, and thereafter declining numbers in September. Ae. epactius adults were collected repeatedly in BG-Sentinel traps in all four study communities; this is the first recorded collection of this species with a trap aiming specifically to collect human-biting mosquitoes. We also present the first description of the temporal abundance pattern for Ae. epactius across an elevation gradient: peak abundance was reached in mid-July in the lowest elevation community (Rio Blanco) but not until mid-September in the highest elevation one (Puebla City). Finally, we present data for meteorological conditions (mean temperature and rainfall) in the examined communities during the study period, and for a cumulative measure of the abundance of adults over the full sampling period. PMID- 25118406 TI - Effect of diet quality on survival and reproduction of adult Paederus fuscipes (Coleoptera: Staphylinidae). AB - The survival and reproduction of the beetle Paederus fuscipes Curtis on diets that differed in macronutrient composition were investigated in the laboratory. The sex organs of females fed each test diet were dissected to evaluate the ovarian development over time. Adults fed on a carbohydrate-rich diet lived longer than adults fed the other diets, but this diet provided insufficient nutrients for reproduction. Females fed on a protein-rich diet had high fecundity; however, the mean longevity of reproductive adult P. fuscipes significantly was shortened by 20-30 d compared with longevity of 60-70 d for adults fed a carbohydrate-rich diet. In contrast, adults that were provided lipid rich diet had low survival and fecundity. Overall, the development ofprevitellogenic follicles was significantly affected by diet regime and days since starting a particular diet. The follicle size of females given protein-rich diet increased 0.5-fold 2 wk after beginning the diet. In contrast, the development of the follicles was slow in females given the carbohydrate-rich diet and the follicles degenerated in females given the lipid-rich diet. In terms of ovarian maturation, females fed on a protein-rich diet contained mostly vitellogenic and chorionated follicles. In contrast, the ovarioles of females on the carbohydrate-rich diet were largely occupied with previtellogenic and vitellogenic follicles, whereas for a lipid-rich diet, the follicles remained at the previtellogenic stage throughout the experiment. PMID- 25118407 TI - Seasonal and spatial oviposition activity of Aedes albopictus (Diptera: Culicidae) in Adriatic Croatia. AB - Seasonal and spatial ovipositional activity of Aedes albopictus (Skuse, 1894) was investigated in Split, South Croatia. During 2009 and 2010, 35 oviposition traps were used in this research. For studying oviposition behavior, mean egg density and Lloyd's mean crowding were used to define the dispersion of eggs into ovitraps and, together with Taylor's power law, to show aggregation degree. To show monthly distribution of egg density, Kriging interpolation was used. Oviposition activity started in April (week 13) and was completed at the beginning December (week 48). Mean egg density reaches the highest values from June to early September (week 25-35). Slope of regressions (mean crowding on mean density and log variance and log mean density) indicated a clumped distribution of eggs. Sampling sites were divided in four groups based on quartiles of median and maximum of mean density. There was no significant difference in measured abiotic factors (temperature, humidity, and rainfall) and measured mean egg density, total amount of eggs, and percentage of positive ovitraps between investigated years, except in mean egg density in some localities. PMID- 25118409 TI - The relationship between deer density, tick abundance, and human cases of Lyme disease in a residential community. AB - White-tailed deer (Odocoileus virginianus Zimmerman), serve as the primary host for the adult blacklegged tick (Ixodes scapularis Say), the vector for Lyme disease, human babesiosis, and human granulocytic anaplasmosis. Our objective was to evaluate the degree of association between deer density, tick abundance, and human cases of Lyme disease in one Connecticut community over a 13-yr period. We surveyed 90-98% of all permanent residents in the community six times from 1995 to 2008 to document resident's exposure to tick-related disease and frequency and abundance of deer observations. After hunts were initiated, number and frequency of deer observations in the community were greatly reduced as were resident reported cases of Lyme disease. Number of resident-reported cases of Lyme disease per 100 households was strongly correlated to deer density in the community. Reducing deer density to 5.1 deer per square kilometer resulted in a 76% reduction in tick abundance, 70% reduction in the entomological risk index, and 80% reduction in resident-reported cases of Lyme disease in the community from before to after a hunt was initiated. PMID- 25118408 TI - Relative humidity and activity patterns of Ixodes scapularis (Acari: Ixodidae). AB - Laboratory studies have shown clear relationships between relative humidity (RH) and the activity and survival of Ixodes scapularis Say (blacklegged tick). However, field studies have produced conflicting results. We examined this relationship using weekly tick count totals and hourly RH observations at three field sites, stratified by latitude, within the state of Rhode Island. Records of nymphal tick abundance were compared with several RH-related variables (e.g., RH at time of sampling and mean weekly daytime RH). In total, 825 nymphs were sampled in 2009, a year of greater precipitation, with a weighted average leaf litter RH recorded at time of sampling of 85.22%. Alternatively, 649 nymphs were collected in 2010, a year of relatively low precipitation, and a weighted average RH recorded at time of sampling was 75.51%. Negative binomial regression analysis of tick count totals identified cumulative hours < 82% RH threshold as a significant factor observed in both years (2009: P = 0.0037; 2010: P < 0.0001). Mean weekly daytime RH did not significantly predict tick activity in either year. However, mean weekly daytime RH recorded with 1-wk lag before sample date was a significant variable (P = 0.0016) in 2010. These results suggest a lag effect between moisture availability and patterns of tick activity and abundance. Differences in the relative importance of each RH variable between years may have been due to abnormally wet summer conditions in 2009. PMID- 25118410 TI - Comparison of efficacy of five types of long-lasting insecticidal nets against Anopheles fluviatilis, the primary malaria vector in east-central India. AB - Five types of long-lasting insecticidal nets (LNs), namely, Olyset, Netprotect, PermaNet, DuraNet, and Interceptor, were tested after 20 washes for efficacy in terms of mortality, deterrence effect, blood-feeding inhibition, and induced exophily of the malaria vector Anopheles fluviatilis in experimental huts in Malkangiri district of Odisha State, India. Efficacy of the three synthetic pyrethroids (SPs) used in the LNs was also analyzed. Use of LNs reduced the entry of An. fluviatilis into the huts by 73.3-83.2%, and the five LNs were comparable in terms of deterrence. The exit rate of An. fluviatilis from the huts with untreated net was 56.3%, and relative to this, Olyset followed by DuraNet induced significantly a higher exophily. In contrast, the exit rate was significantly lower with Interceptor. Among the three SPs, permethrin induced significantly greater exophily relative to the untreated control, and as a result of this, permethrin-treated Olyset produced a lower mortality. Blood-feeding rate of An. fluviatilis was significantly lower with all the five LNs than the control. Similarly, all the three SPs significantly inhibited blood feeding compared with the control. Interceptor and DuraNet, both alphacypermethrin-treated LNs, caused relatively a higher mortality of An. fluviatilis than the other LNs. The five brands of LNs and three SPs tested in the current study were equally effective in terms of deterrence and blood-feeding inhibition; only exiting and killing effect differed among them. Permethrin-treated LNs induced greater exophily, while, overall, alphacypermethrin-treated LNs killed more An. fluviatilis that entered the huts. Advantage of deterrence, excito-repellent, and killing effects of LNs and appropriate selection of SP for net treatment are discussed in this paper. PMID- 25118411 TI - Multiplex qPCR assay for identification and differentiation of Amblyomma americanum, Amblyomma cajennense, and Amblyomma maculatum (Ixodida: Ixodidae) tick species in the eastern United States. AB - Many ticks of the genus Amblyomma are vectors of human pathogens, and the correct species identification is medically and epidemiologically important. Morphological identification is time-consuming and requires a high level of expertise. Identification of engorged, immature, or damaged ticks and the differentiation of closely related species remain problematic. Here, we report the development of a real-time TaqMan assay for the genomic identification and differentiation of Amblyomma americanum (L.), Amblyomma cajennense (F.), and Amblyomma maculatum (Koch), which are human-biting species found in the eastern United States. New species-specific sets of oligonucleotides for the multiplex reaction that detect and differentiate the ITS2 genomic regions of three target species were designed using Visual OMP; the previously published A. americanum oligonucleotide set was also incorporated into our assay. Specificity and sensitivity tests for two multiplex master mixes using different A. americanum sets were performed using individual and pooled samples of adult, nymphal, and larval ticks, and optimization procedures were applied. The multiplex assay successfully differentiates between genomes of three target species and does not cross-react with DNAs of ticks from other genera. Rare cases of nonspecific amplification occurred with DNAs of A. imitator and Amblyomma triste Koch misidentified as A. americanum and A. maculatum, respectively. However, this cross-reaction does not diminish the usefulness of the developed assay east of the 95th meridian, where neither A. imitator nor A. triste are found. Two master mixes incorporating the previously published or newly developed A. americanum sets are being recommended for identification of individual ticks or pooled samples, respectively. PMID- 25118412 TI - Enhanced toxicity of binary mixtures of Bacillus thuringiensis subsp. israelensis and three essential oil major constituents to wild Anopheles sinensis (Diptera: Culicidae) and Aedes albopictus (Diptera: Culicidae). AB - An assessment was made of the toxicity of 12 insecticides and three essential oils as well as Bacillus thuringiensis subsp. israelensis (Bti) alone or in combination with the oil major constituents (E)-anethole (AN), (E) cinnamaldehyde (CA), and eugenol (EU; 1:1 ratio) to third instars of bamboo forest-collected Aedes albopictus (Skuse) and rice paddy field-collected Anopheles sinensis Wiedemann. An. sinensis larvae were resistant to various groups of the tested insecticides. Based on 24-h LC50 values, binary mixtures of Bti and CA, AN, or EU were significantly more toxic against Ae. albopictus larvae (0.0084, 0.0134, and 0.0237 mg/liter) and An. sinensis larvae (0.0159, 0.0388, and 0.0541 mg/liter) than either Bti (1.7884 and 2.1681 mg/liter) or CA (11.46 and 18.56 mg/liter), AN (16.66 and 25.11 mg/liter), or EU (24.60 and 31.09 mg/liter) alone. As judged by cotoxicity coefficient (CC) and synergistic factor (SF), the three binary mixtures operated in a synergy pattern (CC, 140.7-368.3 and SF, 0.0007-0.0010 for Ae. albopictus; CC, 75.1-245.3 and SF, 0.0008-0.0017 for An. sinensis). Global efforts to reduce the level of highly toxic synthetic insecticides in the aquatic environment justify further studies on the binary mixtures of Bti and essential oil constituents described, in particular CA, as potential larvicides for the control of malaria vector mosquito populations. PMID- 25118413 TI - X-ray-induced sterility in Aedes albopictus (Diptera: Culicidae) and male longevity following irradiation. AB - The mosquito Aedes albopictus (Skuse, 1895) is a potent vector of several arboviral diseases, most notably chikungunya and dengue fever. In the context of the sterile insect technique (SIT), the sterilization of the male mosquitoes before their release can be achieved by gamma-ray irradiation. As gamma-ray irradiators are becoming increasingly problematic to purchase and transport, the suitability of an X-ray irradiator as an alternative for the sterilization of Ae. albopictus males was studied. The sterilization of up to 200,000 pupae at one time can be achieved with relative ease, and the sterility results obtained were comparable with those achieved by gamma irradiation, where 99% sterility is induced with a dose of 40 Gy. A significant reduction of longevity was observed in the latter stages of the males' life after irradiation treatments, especially at doses > 40 Gy, which is consistent with the negative effects on longevity induced by similar radiation doses using gamma rays. Females irradiated at 40 Gy were not only 100% sterile, but also failed to oviposit entirely, i.e., all of the females laid 0 eggs. Overall, it was found that the X-ray irradiator is generally suitable for the sterilization process for sterile insect technique programs, as it showed a high processing capacity, practicality, high effectiveness, and reproducibility. PMID- 25118414 TI - Predation and control efficacies of Misgurnus mizolepis (Cypriniformes: Cobitidae) toward Culex pipiens molestus (Diptera: Culicidae) and fish toxicity of temephos in laboratory and septic tank conditions. AB - Culex pipiens molestus Forskal (Diptera: Culicidae) is the dominant mosquito species in septic tanks in South Korea. An assessment was made of the biological control potential of mud loaches, Misgurnus mizolepis Gunther (Cypriniformes: Cobitidae), toward Cx. p. molestus larvae in laboratory and septic tanks. Results were compared with those of temephos 20% emulsifiable concentrate. In laboratory tests, all mud loaches survived on sedimentation chamber- and effluent chamber collected water of aerobic septic tanks (ASTs), whereas all mud loaches died within 3-12 h after introduction into sedimentation chamber- and effluent chamber collected water of anaerobic septic tanks, Gill hyperplasia and hemorrhages at the bases of pectoral fins were detected in all dead mud loaches. These appeared to have been caused by bacterial disease, rather than the physical and chemical characteristics of the septic tank water. A mud loach consumed an average range of 1,072-1,058 larvae of Cx. p. molestus in the AST water at 24 h. At the manufacturer's recommended rate (10 ml/ton) in the AST water, the temephos formulation did not cause fish mortality. In the AST experiment, predation of mosquito larvae by mud loaches at a release rate of one fish per 900 mosquito larvae resulted in complete mosquito control from the third day after treatment throughout the 18-wk survey period, compared with temephos 20% emulsifiable concentrate-treated AST water (reduction rate, 40% at 28 days after treatment). Reasonable mosquito control in aerobic septic tanks can be achieved by mosquito breeding season stocking of a rate of one mud loach per 900 mosquito larvae. PMID- 25118415 TI - Chemical composition, larvicidal, and biting deterrent activity of essential oils of two subspecies of Tanacetum argenteum (Asterales: Asteraceae) and individual constituents against Aedes aegypti (Diptera: Culicidae). AB - Water-distilled essential oils from dried aerial parts of Tanacetum argenteum (Lam.) Willd. subsp. argenteum (Lam.) and T. argenteum (Lam.) Willd. subsp. canum (C. Koch) Grierson were analyzed by gas chromatography and gas chromatography mass spectrometry. In total, 27 and 32 components were identified representing 97.2 and 98.7% of essential oils of subsp. argenteum and canum, respectively. Main compounds of T. argenteum subsp. argenteum were alpha-pinene (67.9%) and beta-pinene (4.8%), whereas alpha-pinene (53.6%), 1, 8-cineole (14.8%), and camphor (4.7%) were the major constituents of subsp. canum. Essential oil of T. argenteum subsp. canum at 10 microg/cm2 with Biting Deterrent Index (BDI) value of 0.73 showed activity similar to N,N-Diethyl-meta-toluamide (DEET) at 25 mol/cm2, whereas the activity of essential oil of subsp. argenteum was lower (BDI = 0.47) than subsp. canum and DEET. Based on 95% CIs, activity of beta caryophyllene (BDI value = 0.54) and caryophyllene oxide (BDI = 0.66) were significantly lower than DEET. In larval bioassays, essential oil of T. argenteum subsp. argenteum showed LC50 value of 93.34 ppm, whereas T. argenteum subsp. canum killed only 40% of the larvae at the highest dose of 125 ppm. Among the pure compounds, beta-caryophyllene (LC50 = 26 ppm) was the most potent compound followed by caryophyllene oxide (LC50 = 29 ppm), which was also similar to (-) beta-pinene (LC50 = 35.9 ppm) against 1-d-old Ae. aegypti larvae at 24-h post treatment. Compounds (-)-alpha-pinene and (+)-beta-pinene showed similar larvicidal activity. Activity of (+)-alpha-pinene with LC50 value of was similar to the essential oil of T. argenteum subsp. argenteum. PMID- 25118416 TI - A user friendly method to assess Anopheles stephensi (Diptera: Culicidae) vector fitness: fecundity. AB - Fecundity, bloodmeal size, and survival are among the most important parameters in the overall fitness of mosquitoes. Impact of an intervention that affects fecundity can be assessed by directly counting the eggs laid by exposed mosquitoes, which is usually done manually. We have developed a macroinstruction, which can be used to count thousands of Anopheles stephensi Liston eggs in a few minutes, to provide an alternative and adaptable method to egg counting as a measure of fecundity. The macro was developed using a scanner and a computer running AxioVision Rel. 4.8 software, a freely accessible software compatible with Windows XP/7/Vista. Using this semiautomated method, it is possible to reduce time, avoid human error and bias, and obtain improved consistency in studies measuring mosquito fecundity. PMID- 25118417 TI - Laboratory and field evaluation of spinosad formulation Natular T30 against immature Culex mosquitoes (Diptera: Culicidae). AB - Spinosad consisting of spinosyn A and D is derived from a naturally occurring, soil-dwelling bacterium, Saccharopolyspora spinosa. Spinosyns are neurotoxins that activate postsynaptic nicotinic acetylcholine and gamma-aminobutyric acid receptors and cause rapid excitation of the insect nervous system and ultimately exhaustion and death of the targets. During the past 30 yr, numerous spinosad based formulations have been developed and applied to control various arthropod pests of agricultural importance. Natular T-30 is a new slow-release formulation containing 8.33% spinosad for use in mosquito larval control programs. High-level larvicidal activity, as indicated by low LC50 and LC90 levels, was demonstrated against Culex quinquefasciatus Say in the laboratory. Larvicidal efficacy was evaluated in semifield microcosms, field mesocosms, and underground storm drains. Fair performance against larval populations of Culex spp. and other mosquito species was achieved, although low efficacy during the initial few days posttreatment was encountered. This slow-release formulation will play an important role in controlling mosquitoes in persistent breeding sources. PMID- 25118418 TI - Exploring new thermal fog and ultra-low volume technologies to improve indoor control of the dengue vector, Aedes aegypti (Diptera: Culicidae). AB - Control of the mosquito vector, Aedes aegypti (L.), inside human habitations must be performed quickly and efficiently to reduce the risk of transmission during dengue outbreaks. As part of abroad study to assess the efficacy of dengue vector control tools for the U.S. Military, two pesticide delivery systems (ultra-low volume [ULV] and thermal fog) were evaluated for their ability to provide immediate control of Ae. aegypti mosquitoes with a contact insecticide inside simulated urban structures. An insect growth regulator was also applied to determine how well each sprayer delivered lethal doses of active ingredient to indoor water containers for pupal control. Mortality of caged Ae. aegypti, pesticide droplet size, and droplet deposition were recorded after applications. In addition, larval and pupal mortality was measured from treated water samples for 4 wk after the applications. The ULV and the thermal fogger performed equally well in delivering lethal doses of adulticide throughout the structures. The ULV resulted in greater larval mortality and adult emergence inhibition in the water containers for a longer period than the thermal fogger. Therefore, the ULV technology is expected to be a better tool for sustained vector suppression when combined with an effective insect growth regulator. However, during a dengue outbreak, either delivery system should provide an immediate knockdown of vector populations that may lower the risk of infection and allow other suppression strategies to be implemented. PMID- 25118420 TI - First record of Ixodes arboricola (Ixodida: Ixodidae) from Turkey with presence of Candidatus Rickettsia vini (Rickettsiales: Rickettsiaceae). AB - Birds are the specific hosts of many tick species and may contribute to the dissemination of ticks and tick-borne pathogens throughout the world. Determination of ticks infesting birds and their pathogens are important for the detection of natural foci of human pathogens. Unfortunately, there is very limited information about the occurrence of ticks on birds and associated pathogens in Turkey. We performed a tick survey on three passerine bird species; Parus major, Sylvia atricapilla, and Turdus merula. Ticks collected from these birds were identified to species and tested for the presence of Borrelia, Ehrlichia, and Rickettsia species. Ixodes arboricola Schulze & Schlottke, Ixodes frontalis Panzer, and Ixodes ricinus L. were found on the birds. This is the first study reporting the presence of I. frontalis and I. arboricola on S. atricapilla and P. major, respectively, in Turkey. In addition, the results of polymerase chain reaction (PCR) with primers specific for gltA and ompA genes and DNA sequence analysis of positive PCR products indicated the presence of Candidatus Rickettsia vini in I. arboricola ticks. In conclusion, this is the first record of both I. arboricola and Candidatus Rickettsia vini in Turkey. Therefore, future studies needed to be conducted on the ticks infesting birds and their pathogens to elucidate the role of birds in the dispersal of tick species and tick-borne pathogens in Turkey. PMID- 25118419 TI - Feeding by Amblyomma maculatum (Acari: Ixodidae) enhances Rickettsia parkeri (Rickettsiales: Rickettsiaceae) infection in the skin. AB - Rickettsia parkeri Luckman (Rickettsiales: Rickettsiaceae), a member of the spotted fever group of Rickettsia, is the tick-borne causative agent of a newly recognized, eschar-associated rickettsiosis. Because of its relatively recent designation as a pathogen, few studies have examined the pathogenesis of transmission of R. parkeri to the vertebrate host. To further elucidate the role of tick feeding in rickettsial infection of vertebrates, nymphal Amblyomma maculatum Koch (Acari: Ixodidae) were fed on C3H/HeJ mice intradermally inoculated with R. parkeri (Portsmouth strain). The ticks were allowed to feed to repletion, at which time samples were taken for histopathology, immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) for rickettsial quantification, and reverse transcriptase polymerase chain reaction (RT-PCR) for expression of Itgax, Mcp1, and Il1beta. The group of mice that received intradermal inoculation of R. parkeri with tick feeding displayed significant increases in rickettsial load and IHC staining, but not in cytokine expression, when compared with the group of mice that received intradermal inoculation of R. parkeri without tick feeding. Tick feeding alone was associated with histopathologic changes in the skin, but these changes, and particularly vascular pathology, were more pronounced in the skin of mice inoculated previously with R. parkeri and followed by tick feeding. The marked differences in IHC staining and qPCR for the R. parkeri with tick feeding group strongly suggest an important role for tick feeding in the early establishment of rickettsial infection in the skin. PMID- 25118421 TI - Detection of bacterial agents in Amblyomma americanum (Acari: Ixodidae) from Georgia, USA, and the use of a multiplex assay to differentiate Ehrlichia chaffeensis and Ehrlichia ewingii. AB - Amblyomma americanum, the lone star tick, is the most common and most aggressive human biting tick in the Southeastern United States. It is known to transmit the agents of human ehrlichioses, Ehrlichia chaffeensis and Ehrlichia ewingii. In addition, it carries agents of unspecified pathogenicity to humans, including Rickettsia amblyommii, Borrelia lonestari, and the newly emerging Panola Mountain Ehrlichia (PME). Surveillance of these ticks for recognized or emerging pathogens is necessary for assessing the risk of human infection. From 2005 to 2009, we surveyed A. americanum ticks from four locations in the state of Georgia. Ticks (1,183 adults, 2,954 nymphs, and 99 larval batches) were tested using a multiplex real-time polymerase chain reaction (PCR) assay designed to detect and discriminate DNA from Rickettsia spp., E. chaffeensis, and E. ewingii. This assay was capable of detecting as few as 10 gene copies of the aforementioned agents. Ticks were also tested for PME and B. lonestari by nested PCR. The prevalence of infection ranged from 0 to 2.5% for E. chaffeensis, 0 to 3.9% for E. ewingii, 0 to 2.2% for PME, 17 to 83.1% for R. amblyommii, and 0 to 3.1% for B. lonestari. There were 46 (4.1%) individual adults positive for two agents, and two females that were each positive for three agents. Two larval batches were positive for both B. lonestari and R. amblyommii, indicating the potential for transovarial transmission of both agents from a single female. Although infrequent in occurrence, the dynamics of coinfections in individual ticks should be explored further, given the potential implications for differential diagnosis and severity of human illness. PMID- 25118422 TI - Efficacy of novaluron as a feed-through for control of immature horn flies, house flies, and stable flies (Diptera: Muscidae) developing in cow manure. AB - Two rates (0.4 mg/kg body weight/d and 0.6 mg/kg body weight/d) of a daily feed through formulation of novaluron (Novaluron 0.67% active ingredient Cattle Mix), a newer benzoylphenyl urea insecticide, were evaluated for efficacy in controlling the larval stage of horn flies, Haematobia irritans (L.), house flies, Musca domestica L., and stable flies, Stomoxys calcitrans (L.), developing in cow manure. Both rates of feed-through novaluron, delivered consecutively for 10 d, reduced adult emergence of all three species when compared with the untreated control. The presence of deformed puparia indicated that novaluron had an insect growth regulator effect on the developing fly larvae. Both of the feed through rates evaluated resulted in 100% reduction of adult stable fly emergence after the second day of feed-through treatment. The level of control efficacy observed against these three fly species make this feed-through formulation a candidate for use in an integrated livestock pest management program, particularly in confined cattle production situations where a feed-through product could be easily administered. PMID- 25118423 TI - A silicone membrane for in vitro feeding of Ixodes scapularis (Ixodida: Ixodidae). AB - We describe a simple silicone membrane for in vitro feeding of Ixodes scapularis (Say), the main tick vector of Lyme borreliosis in the United States. Membranes are prepared using regenerated cellulose lens paper, which is coated with a controlled layer of silicone by submerging and removing the paper in a defined solution of silicone glue dissolved in toluene. Median engorged weight obtained by I. scapularis fed on defibrinated bovine blood using these membranes was 109 mg (32-198 mg). These ticks laid eggs in the laboratory and larvae hatched 6 wk later. This method simplifies artificial membranes for in vitro feeding of ixodid ticks, which have long required a considerable amount of skill and experience to prepare. PMID- 25118424 TI - Feeding host range of Aedes albopictus (Diptera: Culicidae) demonstrates its opportunistic host-seeking behavior in rural Singapore. AB - Aedes albopictus (Skuse) is a competent vector of arboviruses of public health importance, including dengue virus (DENV) and chikungunya virus viruses. Ae. albopictus is the primary vector of chikungunya virus in Singapore. However, despite being ubiquitous, it plays a secondary role in DENV transmission. The vectorial capacity of Ae. albopictus for DENV in field settings appears to be weak because dengue primarily occurs in Aedes aegypti (L.)-dominated, urban settings of the country. As host-seeking behavior is one of the determinants of vectorial capacity, we screened 6,762 female Ae. albopictus from rural, semiurban, and urban locations in Singapore for avian and nonavian bloodmeals using two polymerase chain reaction-sequencing assays developed in-house. The majority (83.2%, n = 79) of bloodmeals from rural and semiurban areas were from humans. However, Ae. albopictus was also found to feed on shrews, swine, dogs, cats, turtles, and multiple hosts in rural settings. In urban areas, all positive bloodmeals were from humans. There were no avian bloodmeals. Our findings testify that Ae. albopictus is highly anthropophagic even in rural settings, but become opportunistic in extremely low human abundance. This opportunistic feeding behavior warrants further investigations into the vectorial capacity of Ae. albopictus to assess its role in arbovirus transmission in endemic habitats. PMID- 25118425 TI - Temporal correlations between mosquito-based dengue virus surveillance measures or indoor mosquito abundance and dengue case numbers in Merida City, Mexico. AB - Surveillance of dengue virus (DENV) in Aedes (Stegomyia) aegypti (L.) females is of potential interest because human DENV infections are commonly asymptomatic, which decreases the effectiveness of dengue case surveillance to provide early warning of building outbreaks. Our primary aim was to examine if mosquito-based virological measures--monthly percentages of examined Ae. aegypti females infected with DENV or examined homes from which at least one DENV-infected Ae. aegypti female was collected--are correlated with reported dengue cases in the same or subsequent months within study neighborhoods in Meida City, Mexico. The study encompassed approximately 30 neighborhoods in the southern and eastern parts of the city. Mosquitoes were collected monthly over a 15-mo period within study homes (average of 145 homes examined per month); this produced approximately 5,800 Ae. aegypti females subsequently examined for DENV RNA. Although monthly dengue case numbers in the study neighborhoods varied > 100-fold during the study period, we did not find statistically significant positive correlations between monthly data for mosquito-based DENV surveillance measures and reported dengue cases in the same or subsequent months. Monthly average temperature, rainfall, and indoor abundance of Ae. aegypti females were positively correlated (P < or = 0.001) with dengue case numbers in subsequent months with lag times of 3-5, 2, and 1-2 mo, respectively. However, because dengue outbreak risk is strongly influenced by serotype-specific susceptibility of the human population to DENV, the value of weather conditions and entomological indices to predict outbreaks is very limited. Potential ways to improve the sensitivity of mosquito-based DENV surveillance are discussed. PMID- 25118426 TI - Effects of azadirachtin on the biology of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) adult female, the main vector of American visceral leishmaniasis. AB - The effects of azadirachtin A added to the sucrose diet of the adult females on the mortality, oviposition, and hatching of the sand fly vector of American visceral leishmaniasis Lutzomyia longipalpis (Lutz & Neiva, 1912) were investigated. Concentrations of 0.1, 1.0, and 10.0 microg/mg of azadirachtin significantly increased insect mortality in comparison with control insects. The same dose also significantly reduced oviposition but not hatching. After a long development period, significantly fewer adult insects were obtained from eggs hatching by azadirachtin-treated females in a dose-response manner. These results indicate that azadirachtin is a potent sterilizer that could be used against the development of Lu. longipalpis populations and as a tool for studying physiological and biochemical processes in phlebotomine species. PMID- 25118427 TI - Attractive toxic sugar baits mixed with pyriproxyfen sprayed on plants against adult and larval Aedes albopictus (Diptera: Culicidae). AB - The effect of spraying a mixture of the insect growth regulator (IGR) pyriproxyfen (1 mg/liter) and either 1% boric acid sugar bait or eugenol sugar bait on croton petra plants (Codiaeum variegatum L.) was evaluated against the container-inhabiting mosquito, Aedes albopictus (Skuse). Treatments were applied to plants and evaluated against adult and larval Ae. albopictus in the laboratory through contact and wash off experiments, respectively. The control treatment lacked an active ingredient and were treated with an attractive sugar bait. The plants treated with attractive toxic sugar baits plus the IGR resulted in 60-100% mortality of laboratory-reared adult Ae. albopictus. The pyriproxyfen solutions collected from the plant wash experiment resulted in 80-100% emergence inhibition to the exposed third- and fourth-instar larvae, compared with the untreated control. Attractive toxic sugar baits mixed with the IGR not only provide effective control of adult mosquitoes, but also provide additional control of larval mosquitoes after being washed off from the treated plants. PMID- 25118428 TI - New strains of Culex flavivirus isolated in Argentina. AB - Strains of Culex flavivirus (CxFV), an insect virus isolated initially from Japan, were isolated from different species of Culex sp. mosquitoes collected in Corrientes province, Argentina, during 2009. CxFV was detected by reverse transcription polymerase chain reaction and by isolation in C6/36 cell culture. Phylogenetic analysis of nucleotide sequences showed that these strains are related closely to a CxFV strain isolated from Trinidad. Our study represents the first report of CxFV isolation and characterization in Argentina from the same geographic area where West Nile Virus has been detected. Further evaluation and viral competition studies will be necessary to determine the impact of this insect flavivirus on an infection caused by other pathogenic flaviviruses. PMID- 25118429 TI - Peer Assistance Services. PMID- 25118430 TI - Prescription drug abuse does not discriminate. PMID- 25118431 TI - Marijuana legalization in Colorado: a nursing student's perspective. PMID- 25118432 TI - Affordable care. PMID- 25118433 TI - Annual address of the President of the State Medical Society of Wisconsin: commercialism. 1914. PMID- 25118434 TI - Pediatrician's passion evolves into center for childhood safety. PMID- 25118435 TI - Data sharing needed to increase quality and decrease costs. PMID- 25118436 TI - The Wisconsin Pharmacy Quality Collaborative--a team-based approach to optimizing medication therapy outcomes. AB - The Wisconsin Pharmacy Quality Collaborative is an initiative of the Pharmacy Society of Wisconsin, which connects community pharmacists with patients, physicians, and health plans to improve the quality and reduce the cost of medication use across Wisconsin. In 2012, the Pharmacy Society of Wisconsin received a $4.1 million Health Care Innovation Award from the Centers for Medicare and Medicaid Services to expand the Wisconsin Pharmacy Quality Collaborative statewide. The aims of the Health Care Innovation Award are to help reduce health care costs in Wisconsin by over $20 million and improve health and health outcomes during the 3-year project period. Methods include implementing a redesign of community pharmacy practices and facilitating medication management services, which include intervention-based services and comprehensive medication review and assessment visits for eligible commercial and Wisconsin Medicaid members. The goals of the project are to: (1) improve medication use among participating patients; (2) improve patient safety; (3) reduce health care costs for participating patients and payers; and (4) establish partnerships between pharmacists and physicians to enhance health outcomes. PMID- 25118437 TI - Ocular trauma resulting in enucleation: A 12-year experience from a large regional institution. AB - PURPOSE: To review the frequency and cause of traumatic enucleation at the University of Wisconsin. METHODS: A 12-year retrospective chart review (2000 2012) from the University of Wisconsin Hospital and Clinics of patients who underwent enucleation following ocular trauma with specimens submitted to the University of Wisconsin Eye Pathology Laboratory. RESULTS: A total of 188 eyes enucleated following ocular trauma were identified between 2000 and 2012. One hundred eleven (59%) cases had an identifiable mechanism of injury recorded in the medical record and were included in the final analysis. The overall median patient age was 41 years with 83.8% male. Assault was the most common reason for enucleation (n=30, 27.0%) of which 15 (13.5%) cases were related to gunshot wounds. Other causes included outdoor or recreational activities (n = 20, 18.0%), fall (n = 14, 12.6%), non-motor vehicle accidents (n = 6, 5.5%), motor vehicle accidents (n = 15, 13.5%), work-related injury (n = 15, 13.5%), and sports related injury (n = 11, 10%). CONCLUSION: Assault is the most common cause of traumatic ocular injury leading to enucleation. Gunshot and stab wounds were responsible for the majority of these cases. Men were much more likely to undergo enucleation due to ocular trauma with the exception being that caused by falls, where the rate was nearly equal between men and women. PMID- 25118438 TI - The Wisconsin immunization registry experience: comparing real-time and batched file submissions from health care providers. AB - CONTEXT: The Wisconsin Immunization Registry is a confidential, web-based system used since 1999 as a centralized repository of immunization information for Wisconsin residents. OBJECTIVE: Provide evidence based on Registry experiences with electronic data exchange, comparing the benefits and drawbacks of using the Health Level 7 standard, including the option for real time data exchange vs the flat file method. DESIGN: For data regarding vaccinations received by children aged 4 months through 6 years with Wisconsin addresses that were submitted to the Registry during 2010 and 2011, data timeliness (days from vaccine administration to date information was received) and completeness (percentage of records received that include core data elements for electronic storage) were compared by file submission method. RESULTS: Data submitted using Health Level 7 were substantially more timely than data submitted using the flat file method. Additionally, data submitted using Health Level 7 were substantially more complete for each of the core elements compared to flat file submission. CONCLUSIONS: Health care organizations that submit electronic data to immunization information systems should be aware that the technical decision to use the Health Level 7 format, particularly if real-time data exchange is employed, can result in more timely and accurate data. This will assist clinicians in adhering to the Advisory Committee on Immunization Practices schedule and reducing over-immunization. PMID- 25118439 TI - A clinical, diagnostic, and ecologic perspective on human anaplasmosis in the Upper Midwest. AB - INTRODUCTION: Human anaplasmosis caused by the bacterial pathogen Anaplasma phagocytophilum was first discovered in the Upper Midwest in 1990. Since that time the number of cases in the region has steadily increased, such that today, the pathogen rivals that of Lyme disease in causing human tick-borne-related illness. OBJECTIVE: We provide an overview of the biology, clinical characteristics, and epidemiology of the disease in the Upper Midwest and discuss currently available diagnostic methods. FINDINGS: Rapid differentiation of anaplasmosis from other acute febrile illnesses and targeted treatment are important for preventing severe disease and potentially fatal outcomes in infected individuals. Beyond blood smear analysis and serology, the development of real-time polymerase chain reaction (PCR) assays for clinical use holds promise in improving our ability to make rapid diagnoses and to differentiate A phagocytophilum infections from those produced by closely related Ehrlichia pathogens, which are also present in the region. CONCLUSION: Continuing expansion of the range of the black-legged tick (Ixodes scapuloris), the principal vector of the disease, into areas heavily populated or visited by humans in the region likely will result in this pathogen becoming an even greater burden on human health. Efforts are needed to better characterize the current geographic distribution of human Anaplasma and Ehrlichia cases to identify emerging foci and to better understand the enzootic cycles that maintain the pathogens in the region. Improved diagnostics may assist with such efforts. PMID- 25118440 TI - Idiopathic spontaneous rupture of an intercostal artery. AB - Spontaneous rupture of an intercostal artery is exceptionally rare without an inciting event such as trauma or nontraumatic arterial wall weakening. This report details the diagnosis and treatment of a 47-year-old man who presented with a spontaneous hemothorax from an intercostal artery. There are very few reports in the literature documenting spontaneous intercostal artery rupture without associated illness or injury. PMID- 25118442 TI - Endowment transitions from grantmaker to changemaker. PMID- 25118443 TI - Reach out or drop out. PMID- 25118441 TI - A case of pityriasis amiantacea with rapid response to treatment. AB - Pityriasis amiantacea is a rare cutaneous reaction pattern to various underlying inflammatory diseases of the scalp. The clinical findings are very characteristic but often under-recognized. This condition can lead to scarring alopecia, and can be refractory to conservative treatment. It is therefore important to recognize the condition so that appropriate treatment can be initiated promptly. PMID- 25118445 TI - Just give me a flight plan. How to make IT purchasing more effective. PMID- 25118444 TI - Effective IT purchasing. What top-of-line issues comprise, challenge effective hardware, software purchasing? PMID- 25118446 TI - Revisions to NPSG.15.02.01 on home oxygen use. PMID- 25118447 TI - Revisions to National Patient Safety Goal on home oxygen use. PMID- 25118448 TI - Accepted: Revised hospital and critical access hospital requirements to align with CMS. PMID- 25118449 TI - Joint Commission announces changes in addressing Life Safety Code deficiencies. Effective July 1, 2014: modifications to processing PFIs and equivalencies. PMID- 25118450 TI - Revised: "Human resources" chapter for behavioral health care. PMID- 25118451 TI - Clarification: Joint Commission expecations during IQCP transition. PMID- 25118452 TI - We must convey the message. PMID- 25118453 TI - Be it resolved that the leadership of the MNA...will support Medicare for AII without reservation... PMID- 25118454 TI - Nursing's voice in politics: the ongoing relationship between NURSES and LEGISLATORS. PMID- 25118455 TI - APS leadership meets with NIGMS. PMID- 25118456 TI - Association of Chairs of Departments of Physiology 2013 Survey Results. PMID- 25118457 TI - AAMC Medical School Faculty Compensation Survey. PMID- 25118458 TI - APS supports 75 undergraduate students to conduct physiology laboratory research. PMID- 25118459 TI - Zucker reappointed editor of AJP - Heart and Circulatory Physiology. PMID- 25118461 TI - APS urges OLAW to revise "significant changes" guidance. PMID- 25118460 TI - NIH finalizes chimpanzee housing requirements. PMID- 25118462 TI - NIH to require balanced sex representation in animal and cell studies. PMID- 25118464 TI - Letter to Keneth Baldwin. PMID- 25118463 TI - Following Faraday's footsteps: getting involved in science outreach. PMID- 25118465 TI - Are you INVESTED in NCNA? PMID- 25118466 TI - Legislative update: busy short session. PMID- 25118467 TI - NCNA leadership academy 2014: retreat reflections on leadership. PMID- 25118468 TI - Unexpected inspiration. PMID- 25118469 TI - RIBN conference offered partners/students opportunities to engage. PMID- 25118470 TI - Nursing in concert: 2014 ANA membership assembly. PMID- 25118471 TI - NP history lesson. PMID- 25118472 TI - In your corner. PMID- 25118473 TI - Breast cancer--new aspects of tumor biology: are calcitriol and cyclooxygenase-2 possible targets for breast cancer? AB - Up until now there have been many advances in treatment options for breast cancers such as targeted therapies like monoclonal antibodies, tyrosine kinase inhibitors, mTOR antagonists, and vaccines. Despite these advances, there are still many more that warrant further exploration. Two of these targets might be the cyclooxygenase-2 (COX-2), the key enzyme required to convert arachidonic acid to prostaglandins, and calcitriol [1,25(OH)2D3] which is the biologically active form of vitamin D. Both calcitriol and the inhibition of COX-2 have shown antiproliferative and prodifferentiation, as well as pro-apoptotic effects in different malignancies in vitro and in vivo, and the key prostaglandin catabolic enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is known to have tumor suppressor activity. Furthermore, the combination ofcalcitriol and nonsteroidal anti-inflammatory drugs (NSAIDs), such as non-selective and selective COX-2 inhibitors, acting synergistically to achieve significant cell growth inhibition in prostate cancer. Some epidemiological studies suggest that vitamin D confers a moderate benefit against breast cancer while most epidemiological studies presume that NSAIDs confer the same. Nevertheless there is growing body of evidence that COX-2 expression is a fundamental step in breast cancer carcinogenesis. To date, clinical trials have been conducted in patients with different malignancies using treatment strategies including COX-2 inhibitors and calcitriol and are showing partially encouraging results. The goal of this review is to shed light on the association between the prostaglandin as well as vitamin D metabolism relating to the incidence and therapy of breast cancers. Moreover, this review will also highlight potential treatment options, as well as extract any existing interactions between the two metabolisms. PMID- 25118474 TI - Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature. AB - Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months. PMID- 25118476 TI - Fertility preservation in women with early stage cervical cancer. Review of the literature. AB - Within the last decades, the percentage of diagnosed cervical cancer in women of reproductive age has increased. The possibility of diagnosing small cervical tumors (< or = twocm) in childbearing age, can be explained due to the fact that many women, are aware of the benefits of Pap smear or colposcopy examination. Many demand a more conservative policy to handle such lesions in order to have an uneventful pregnancy in the near future. PMID- 25118475 TI - The importance of alpha/beta (alpha/13) interferon receptors and signaling pathways for the treatment of cervical intraepithelial neoplasias. AB - INTRODUCTION: Immunotherapies have been effective in treating various forms of cancer, including cervical intraepithelial neoplasias (CINs) predominantly caused by human papilloma virus (HPV). DEVELOPMENT: To establish persistent infections in stratified epithelia, HPV induces proliferative lesions. Viral gene products are able to change gene expression and cellular proteins. Interferons (IFNs) are inducible glycoproteins that have immunomodulatory, antiviral, antiproliferative, and antiangiogenic effects. In particular, interferon-alpha (IFN-alpha) has been shown to inhibit the development and progression of cervical cancer. In this review, actions of interferons alpha/beta (alpha/beta), including their receptors and signaling pathways, are described, as well as their clinical importance in the immune response against cervical lesions. CONCLUSION: The interaction of IFN alpha/beta with its receptor results in a series of phosphorylation events. These mechanisms can be ineffective in IFN response, then it can also compromise the therapeutic effects of immunotherapy. PMID- 25118477 TI - Relationship of human papilloma virus multiple genotype infection with patient's age and type of cervical lesion. AB - PURPOSE OF INVESTIGATION: To document the prevalence of infection by multiple genotypes of the human papilloma virus (HPV) in patients with cervical pathology in a study population, and to determine the relationship between multiple genotype infection, age of the patient, and the type of cervical pathology. MATERIALS AND METHODS: Prospective, cross-sectional descriptive study. A total of 1,007 patients were recruited among women seen at the cervical pathology clinic of Sant Joan de Deu University Hospital in Barcelona (Spain) between January 2003 and March 2011. Statistical analyses were done with SPSS v.19 software. Differences between groups were considered statistically significant atp < 0.05. RESULTS: There was 28.3% of the women (286 cases) that were infected by multiple HPV genotypes. The mean number of genotypes identified was 2.52 (range 2 to 8). Mean age of the patients with multiple genotype infection was 32.31 years, and mean age of the patients with single genotype infection was 37.27 years (p < 0.001). The prevalence of infection by multiple HPV genotypes was 28% in patients with cervical intraepithelial neoplasia grade 1 (CIN 1) and 33% in patients with grade CIN 2-3 lesions, and both prevalence rates were significantly higher than in patients with carcinoma (20%) (p = 0.03). CONCLUSIONS: In the present study population the authors found no evidence of higher prevalence of multiple HPV genotype infection in women with carcinoma. Age of women with multiple infection was lower than those with single infection. PMID- 25118478 TI - Predictors of malignancy in endometrial polyps: a multi-institutional cohort study. AB - PURPOSE OF INVESTIGATION: The risk of endometrial cancer in women with endometrial polyps (EPs) has been reported to vary between 0.3% and 4.8%. There is a lack of data about the management of asymptomatic women with incidental diagnosis of EPs. In the present study the authors correlated demographic and clinical characteristics with histopathological features of the EPs hysteroscopically removed. MATERIALS AND METHODS: An observational multi institutional cohort study was conducted from February 2010 to December 2012 to identify all the premenopausal and postmenopausal women consecutively undergoing hysteroscopic polypectomy. The data of women were reviewed and clinical features were related to histopathologic results. RESULTS: The patients recruited were 813. The mean age was 52.5 years (range 22-87). The results showed a correlation between older age, high body mass index (BMI) and obesity, postmenopausal state, abnormal uterine bleeding (AUB), hypertension, and risk of malignant EPs. On multivariable analysis, the correlation remained only for age (OR 1.08, 95% CI 1.03 - 1.14) and AUB (OR 3.53, 95% CI 1.87 - 6.65). CONCLUSION: Older patients in postmenopausal status with AUB, a high BMI, and hypertension are at higher risk for premalignant and malignant polyps. In these patients a surgical approach should be used, consisting in hysteroscopical removing of the polyp. PMID- 25118479 TI - An in vivo model for the study of ovarian cancer and the persistence of characteristic mutations in xenografts. AB - OBJECTIVE: To identify factors affecting xenograft growth of epithelial ovarian cancer (EOC) cells in nude mice and to detect characteristic mutations occurring in the xenografts following serial passage. MATERIALS AND METHODS: A total of 64 human EOCs were subcutaneously inoculated in Balb/c nude mice in order to obtain a series of xenografts. Whole-exome sequencing was analyzed with Agilent SureSelect targeted enrichment capture system and Illumina Solexa Hiseq 2000 sequencing platform. Mutations were confirmed by comparison against the reference genome build 37.3. RESULTS: The tumor take rate was 50% (32/64). TP53 mutation was detected in nine often Type II tumors. BRAF and CTNNB1 were not mutated in any of the samples, and PTEN mutation occurred in only one sample. The present data indicate that advanced stage serous EOCs and early stage non-serous EOCs were easy to grow in nude mice, and xenografts maintained the characteristic mutations. CONCLUSIONS: Advanced stage serous EOCs and early stage non-serous EOCs were easy to grow in nude mice, and xenografts maintained the characteristic mutations. Xenografts in nude mice are useful in vivo models for the study of human EOCs. PMID- 25118480 TI - Toxicity of concurrent chemoradiotherapy for locally advanced cervical cancer. AB - AIM OF THE STUDY: The analysis of acute and late toxicity of concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) based on review of 120 patients treated in Centre of Oncology in Krakow between 2001 and 2007. MATERIALS AND METHODS: Medium age of the patients was 52 years (43-66). Overall, 12 patients (10.0%) were in Stage IB2, 54 (45.0%) in Stage II, 43 (35.8%) in Stage III, and 11 (9.2%) in Stage IVA. Squamous cell carcinoma was present in 114 (95.0%) patients. Well-differentiated (grade 1) tumour was found in 39 (32.5%) patients, moderately differentiated (grade 2) in 41 (34.2%), and poorly differentiated (grade 3) in 40 (33.3%). Karnofsky performance status score was 70 in 72 (60.0%) patients, and 80-90 in 48 (40%). External radiation therapy was delivered with high-energy six to 15 MV photon beams using four-field brick technique. The total dose of 50 Gy was given in 25 fractions within five weeks using standard fractionation. Concurrently with external radiotherapy, six cycles of chemotherapy were administered to all the patients as an intravenous infusion of once-weekly cisplatin 40 mg/m2. On completion of external beam radiotherapy, low-dose rate brachytherapy with tandem and two colpostats was performed to deliver the dose of 40 Gy to point A in two 20 Gy insertions at weekly intervals. RESULTS: Of the 120 patients in the investigated group, 78 (65%) were disease free for five years. Symptoms of acute treatment-related toxicity grade 3 or 4 (WHO) occurred in 21.6% of patients including leucopoenia in 7.5%. anaemia in 5.0%, nausea and vomiting in 3.3%, diarrhea in 5.0%, and urinary tract infection in 0.8%. Full planned treatment (teleradiotherapy + chemotherapy + brachytherapy) completed 78.3% of the group; full planned radiotherapy without full chemotherapy completed 20% of the patients. Late treatment complications of grade 3 or 4 were observed in two (1.6%) patients (narrowing of large intestine requiring surgery and recto-vaginal fistula). CONCLUSIONS: In patients with LACC treated with CCRT, the most frequent acute toxic effects include: haematological disorders (leucopoenia, anaemia), gastrointestinal disorders (nausea and vomiting, diarrhea), vulvo-vaginal disorders, and urinary tract infection. The most frequent late toxic effects included: rectal bleeding, bowel complications requiring surgery, stenosis or recto-vaginal fistula, and haematuria. PMID- 25118481 TI - En-bloc pelvic resection with concomitant rectosigmoid colectomy and immediate anastomosis as part of primary cytoreductive surgery for patients with advanced ovarian cancer. AB - OBJECTIVE: To assess the authors' experiences in en bloc pelvic resection with concomitant rectosigmoid colectomy and primary anastomosis as a part of primary cytoreductive surgery for patients with advanced ovarian cancer. MATERIALS AND METHODS: Atotal of 22 patients with FIGO Stage IIB-IV epithelial ovarian cancer who underwent en bloc pelvic resection with anastomosis were retrospectively reviewed. Data analyses were carried out using SPSS 10.0 and descriptive statistics, Kaplan-Meier survival curves, and Log Rank (Mantel-Cox) test were used for statistical estimations. RESULTS: Median age was 58.8 years. FIGO stage distribution of the patients was; one (4.5%) IIB, three (13.7%) IIC, three (13.7%) IIIA, six (27.3%) IIIB, and nine (40.9%) IIIC. Median peritoneal cancer index (PCI) was 8 (range 5-22) and optimal cytoreduction was achieved in 18 patients (81.8%) of whom 13 (59.1%) had no macroscopic residual disease (complete cytoreduction). There was no perioperative mortality. A total of nine complications occurred in seven (31.8%) patients. Anastomotic leakage was observed in one (4.5%) patient. There was no re-laparotomy. Mean follow-up time was 60 months. There were 15 (68.2%) recurrences of which 12 (80%) presented in extra-pelvic localizations. Mean disease-free survival (DFS) and overall survival (OVS) were estimated as 43.6 and 50.5 months, respectively. Patients with complete cytoreduction had a better DFS (p = 0.006) and OVS (p = 0.003) than those with incomplete cytoreduction. CONCLUSION: En bloc pelvic resection, as a part of surgical cytoreduction, seems to be a safe and effective procedure in many patients with advanced ovarian cancer if required. Despite relatively high general complication rate, anastomosis-related morbidity of this procedure is low as 0.8%. Nevertheless, surgical plan and perioperative care should be personalized according to medical and surgical conditions of the patient. PMID- 25118482 TI - Apparent diffusion coefficient on 3.0 Tesla magnetic resonance imaging and prognostic factors in breast cancer. AB - AIM: The aim of the study was to evaluate whether the apparent diffusion coefficient (ADC) provided by 3.0 Tesla diffusion-weighted imaging (3T DWI) varies with the prognostic factors Ki67 and grading in invasive breast cancer. MATERIALS AND METHODS: Seventy-three patients with 75 invasive breast cancer lesions who had undergone 3.0 Tesla magnetic resonance imaging (MRI) for local staging were enrolled. All lesions were confirmed by histologic and immunohistochemical analysis. MRI included both dynamic contrast-enhanced and DWI sequences. ADC value was obtained for each lesion. Histologic tumor grade was established according to the Nottingham Grading System (NGS), while Ki67 expression was evaluated by MM1 clone IgG1 mouse anti-human monoclonal antibody. Patients were divided into the following groups: grade 1 (G1), grade 2 (G2), grade 1 plus grade 2 (G1+G2) and grade 3 (G3), and low Ki67 (< or = 14%), intermediate Ki67 (15%-30%), and high Ki67 (> or = 30%). ADC values were compared with the G and Ki67 groups. Statistical comparison was carried out using the Mann Whitney U and the Kruskal-Wallis H test. RESULTS: ADC values were significantly higher in G3 than in G1+G2 tumors; no significant difference was observed when G1, G2, and G3 were compared. There was no statistically significant correlation between ADC values and Ki67 percentage (p > 0.05). DISCUSSION: ADC values obtained on 3T DWI correlate with low (G1+G2) and high-grade (G3) invasive breast carcinomas. CONCLUSION: ADC may be a helpful tool for identifying high-grade invasive breast carcinoma. PMID- 25118483 TI - Contrast-enhanced ultrasonography in diagnosis of benign and malignant breast lesions. AB - PURPOSE: This study aims to investigate the value of real-time contrast-enhanced ultrasonography (US) in differentiating benign and malignant breast lumps. MATERIALS AND METHODS: Patients with breast lesions were observed. The enhancement form, intensity, and time-intensity curve were classified, and the characteristics of all the lesions were analyzed. RESULTS: Inhomogeneous partial enhancement and entire enhancement were exhibited in most of the malignant lesions. High enhancements were observed in malignant lesions, whereas lower enhancement and no enhancement were exhibited in the benign tumors. The peak value and regression time were significantly different between the two groups. CONCLUSION: There's a significant difference regarding the results of real-time contrast-enhanced ultrasound between the benign tumor and malignant tumor which would help to improve the diagnostic accuracy of breast neoplasms. PMID- 25118485 TI - Prognostic factors affecting lymph node involvement in cervical cancer. AB - AIM: Clinical and histopathological factors that affect lymph node involvement in cervical cancer and the prognostic importance of these factors were evaluated in this study. MATERIALS AND METHODS: A total of 179 patients were diagnosed with cervical cancer between January 2001 and June 2010 and were included in this study. The patients' charts were evaluated retrospectively and information was collected by reaching 89 patients and asking questions. RESULTS: When the prognostic factors that affect pelvic lymph node involvement were evaluated, increased tumor size and increased invasion depth, presence of lymphovascular area involvement, and an advanced stage were observed to statistically significantly increase pelvic lymph node involvement. No relationship was found between tumor histology and grade; parametrial, endometrial, vaginal involvement, and pelvic lymph node involvement. CONCLUSION: Knowledge of prognostic factors in cervical cancer plays an important role in determining the morbidity and mortality and the treatment strategies. PMID- 25118484 TI - Comparison of pelvic masses score (PMS) and Risk of Malignancy Index (RMI 3) in the evaluation of pelvic masses. AB - PURPOSE: Ovarian cancer is the fourth cause of death from cancer in women worldwide and the majority of its diagnoses is made in an advanced stage of the disease. Several sonographic scoring systems have been created for a better preoperative discrimination between benign and malignant pelvic masses. The aim of this study was to evaluate the performances of the Risk of the Malignancy Index 3 (RMI 3) and the Pelvic Masses Score (PMS). MATERIALS AND METHODS: This retrospective study was performed in 55 women admitted to the department of Obstetrics and Gynecology of University of Udine for surgical exploration of pelvic masses between 2009 and 2012. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both the scores. RESULTS: PMS showed a sensitivity of 100%, a specificity of 93.8%, a PPV of 70%, and a NPV of 100%, while RMI 3 yielded a sensitivity of 85%, a specificity of 91%, a PPV of 60%, and a NPV of 97.8%. CONCLUSION: The authors found that, in discriminating between benign and malignant pelvic disease, the PMS method was more reliable than RMI3. PMS is a simple scoring system which can be used in clinical practice. PMID- 25118486 TI - A survey of Jordanian obstetricians and gynecologists' knowledge and attitudes toward human papillomavirus infection and vaccination. AB - OBJECTIVE: To assess the knowledge and attitudes of Jordanian obstetricians and gynecologists toward human papillomavirus (HPV) infection and its vaccine. MATERIALS AND METHODS: A self-administered, anonymous questionnaire was distributed to 400 participants attending scientific meetings. The survey focused on three areas: knowledge of HPV infection, vaccine, and attitude toward vaccination of female adolescents. RESULTS: Survey response rate was of 72.3%. The vast majority knew most of the statements related to knowledge of HPV infection, 66% thought that conventional screening Pap test have a sensitivity of > 75%, and only 44% of them knew that there are 13 to 17 HPV types that cause cervical cancer. The majority of the respondents (79%) knew that the vaccine would lead to long lasting immunity and 45% of the respondents thought that the vaccination would eliminate the need for regular Pap test. The majority (78%) indicated that the vaccine should be given to girls before the beginning of sexually active life. Overall, 67.5% of respondents intend to prescribe HPV vaccines and 79.6% of the respondents intend to recommend the vaccine if it is publicly funded. CONCLUSION: Most of the gynecologists in Jordan have the intention to recommend HPV vaccine, the deficit in their knowledge of HPV infection and vaccine must be corrected to assure acceptability of the vaccine. PMID- 25118487 TI - Curcumin induces human SKOV3 cell apoptosis via the activation of Rho-kinase. AB - OBJECTIVE: Curcumin has been showed anti-inflammation and anti-cancer effect in various cancer cells such as lung cancer, breast cancer, and so on. However the pro-apoptosis effect and the mechanism of curcumin in ovarian cell is still not very clear. In this study, the authors demonstrated that curcumin induced human SKOV3 cell apoptosis and explored the underlying mechanism concerning Rho A/Rho kinase pathway. MATERIALS AND METHODS: Human SKOV3 cell was performed with MTT assay to measure the cell viability with curcumin. The cell was treatment with 15 microM or 30 microM curcumin and flow cytometry. Cell apoptosis analysis was performed to measure the cell apoptosis level. In order to explore the mechanism concerning pro-apoptosis activity of curcumin, the cells were pre-treatment with Y-27632, a specific Rho-kinase inhibitor, before curcumin was added. Then the expression of activated caspase-3 and Rho A, Rho-kinase was detected by western blot. RESULTS: Treatment with 15 microM or 30 microM curcumin significantly promoted the apoptosis of SKOV3 cell (p < 0.05) and the apoptosis rate is dose dependent. Curcumin also activated the expression of Rho A and Rho-kinase in a dose-dependent effect. When pre-treatment with Y-27632, the expression of activated caspase-3 was significantly decreased compared to the group without Y 27632 pre-treatment (p < 0.05). CONCLUSIONS: Curcumin induced human SKOV3 cell apoptosis in a dose-dependent effect. The pro-apoptosis effect of curcumin is partly mediated via the activation of Rho A/Rho-kinase signal pathway. This may help to further clarify the mechanisms of curcumin in ovarian cancer therapy. PMID- 25118488 TI - Is HE4 a useful endometrioma marker? AB - PURPOSE OF INVESTIGATION: By the comparison between most used tumor marker trend (cancer antigen 125: CA 125 and human epididymal secretory protein E4: HE4) before and after laparoscopic surgery, the aim of the present study was to assess HE4 usefulness in ovarian benign cyst and endometrioma diagnosis. MATERIALS AND METHODS: Thirty-eight patients were enrolled in this prospective study: 25 women underwent unilateral endometriosis ovarian cyst excision, 13 underwent benign ovarian cyst incision, and 26 were healthy controls. CA 125 and HE4 serum levels were estimated before surgery (in the early proliferative phase of the cycle) and one month after surgery. RESULTS: A statistically significant decrease of CA 125 serum level was found after an endometrioma surgical excision but no decreases in HE4 serum level. CONCLUSION: In patients with endometrioma, no alteration was found in HE4 serum levels before and after surgery, while CA125 serum levels decreased after surgery. HE4 may better distinguish a malign cyst from benign one, but it is not useful in the diagnosis of low risk endometrioma. PMID- 25118489 TI - Therapy-related myelodysplastic syndrome and acute myeloid leukemia following chemotherapy (paclitaxel and carboplatin) and radiation therapy in ovarian cancer: a case report. AB - In recent years, the incidence of therapy-related myelodysplastic syndrome (t MDS) and therapy-related acute myeloid leukemia (t-AML) that occur during chemotherapy for ovarian cancer has increased. While alkylating agents and topoisomerase II inhibitors are particularly mutagenic and have strong leukemogenic potential, paclitaxel and combination chemotherapy/radiation therapy also appear to induce t-MDS. The present authors report a case of t-MDS that developed during chemotherapy and radiation therapy for ovarian cancer. The patient was a 75-year-old woman who received six courses of cyclophosphamide/doxorubicin/cisplatin (CAP) therapy after initial surgery for Stage IIIc grade ovarian cancer in 1995. Beginning in February 2005, the patient experienced multiple recurrences due to sternal metastasis. Chemotherapy, including paclitaxel and carboplatin (TC), was administered intermittently and was combined with radiation therapy to a sternal metastatic lesion. Pancytopenia was observed in December 2008, and she was diagnosed with t-MDS (WHO subtype, refractory cytopenias with multilineage dysplasia [RCMD]): the time from first chemotherapy to t-MDS onset was 106 months. Without evidence of blast crisis, the recurrent lesions continued to grow and caused multiple cerebral infarctions, from which she eventually died. The cumulative doses of paclitaxel and carboplatin administered to this patient were 1,968 mg and 6,480 mg, respectively. PMID- 25118490 TI - Rectus abdominis muscle resection and fascial reconstruction for the treatment of uterine leiomyosarcoma invading the abdominal wall: a case report. AB - The authors present a case of intra-abdominal recurrent leiomyosarcoma invading a large area of the abdominal wall. The patient underwent cytoreductive surgery, including resection of the rectus abdominis muscle, followed by reconstruction of the defect using synthetic mesh. The tumor was surgically removed by en bloc resection, including most of the rectus abdominis muscle and ileum. The abdominal wall defect was repaired using synthetic mesh. The patient underwent radiotherapy and chemotherapy after the surgery and was healthy one year later. PMID- 25118491 TI - A case of accessory mammary cancer in a male patient and a literature review. AB - A 68-year-old Chinese male patient was referred to the present hospital because of a right axillary lump in May 2011. Physical examination showed a rigid movable mass measuring 35 mm in diameter in the right axilla. No mass was palpable in either breast. Mammograms were normal. Physical and imaging examination of the head and neck region, lung, and upper and lower gastrointestinal tract also revealed no evidence of a primary tumor. Ultrasonography and resonance imaging (MRI) revealed no evidence of tumors in the bilateral mammary glands. Fine needle histological biopsy for suspected malignancy was performed, and the patient underwent tumor resection with axillary lymph node dissection on Jun 2011. Moderately differentiated adenocarcinoma in ectopic breast tissue was diagnosed based on the pathologic result, the tumor was immunohistochemically positive for ER, PR, and HER-2. PMID- 25118492 TI - Successful treatment of a large symptomatic lymphocyst with percutaneus drainage and repeated iodopovidone sclerotherapy. AB - The objective of the case report was to present an easy and safe method for treatment of a large, persistent lymphocyst, through a procedure performed in an ambulatory setting. The patient diagnosed with large (1,800 mi), symptomatic (pains, renal insufficiency) lymphocyst after lymphadenectomy for cervical cancer, was successfully treated with percutaneous drainage (using vascular drains) and five sessions of sclerotherapy with 10% iodopovidone, performed in ambulatory settings. The method was minimally invasive, safe, and effective in management of symptomatic lymphocyst. PMID- 25118493 TI - Heterologous type of malignant mixed Mullerian tumor of the uterus presenting as a vulvar mass. AB - Carcinosarcoma is a rare, extremely aggressive tumor of the uterus with a poor prognosis. The authors describe a case of a 78-year-old woman who presented with a giant mass protruding through the cervix, vagina, and vulva. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. The histopathological examination of the surgical specimen revealed a malignant mixed Mullerian tumor. The clinical and pathological features, molecular data, and prognosis of this aggressive neoplasm are discussed. Although uterine carcinosarcomas are extremely rare, when a postmenopausal woman with a vulvar mass is admitted to the gynecology clinic, the physician should consider that the mass may be a carcinosarcoma. PMID- 25118494 TI - Uterine endometrial carcinoma with trophoblastic differentiation: a case report with literature review. AB - Choriocarcinoma is categorized as either gestational or nongestational depending on its origin. Nongestational choriocarcinoma originated in the trophoblastic differentiation is a rare but an aggressive tumor. This article reports a nongestational case of a uterine endometrial carcinoma with trophoblastic differentiation. A 54-year-old woman with a history of atypical genital bleeding that underwent semi-radical hysterectomy, bilateral salpingo-oophrectomy, and pelvic lymph nodes dissection. Pathological investigation showed that the tumor had endometrioid adenocarcinoma and choriocarcinomatous components. Although a series of multimodality treatments including craniotomy were performed, she died of aggressive lung and brain metastases one year after the primary surgery. PMID- 25118495 TI - Aggressive angiomyxoma of the female genital tract: report of two cases. AB - Aggressive angiomyxoma (AA) was identified in 1983 and 250 cases of this rare tumor have since been reported in the literature. It is characterized by a locally infiltrative and recurrent nature; however, it rarely shows distant metastasis. Surgical managements can successfully treat AA patients but may result in a significant morbidity due to the large size and infiltration of the tumor. Less radical surgeries have recently been recommended in the treatment of this tumor, but adjuvant therapies have not yet been fully established. The authors report here two AA cases that were treated at their hospital, with a brief review of the literature. PMID- 25118496 TI - Rupture of an endometrioma with extremely high serum CA-125 level (> 10,000 IU/ml) and ascites resembling ovarian cancer. AB - Carbohydate antigen 125 (CA-125) is a type of cell surface glycoproteins present in more than 80% of non-mucinous epithelial ovarian carcinomas; however, benign gynecologic conditions commonly cause a smaller increase in CA-125 level. This report presents the details regarding a 44-year-old woman with extremely high serum CA-125 level and ascites. She complained of having abdominal pain and abdominal distension. Her serum CA-125 level had been markedly elevated (> 10,000 IU!ml) and computed tomograpgy (CT) revealed an ovarian tumor and massive ascites. The cytological analysis showed no evidence of malignancy, however, the positron emission CT (PET-CT) scan suggested ovarian malignancy with peritoneal carcinomatosis. Under the impression that the patient had ovarian cancer, the present surgical team carried out an explorative laparotomy and discovered the ruptured bilateral ovarian endometriomas. In this study, it is suggested that clinicians carrying out differential diagnosis of pelvic mass with high serum CA 125 level and ascites should consider not only ovarian cancer but also ruptured endometrioma. PMID- 25118497 TI - Adenosarcoma of the uterine body initially presenting as an interstitial small tumor of the uterus: a case report. AB - Adenosarcoma of the uterine body is a rare mixed tumor in which a benign epithelial component is mixed with a malignant stromal element. It has been considered that this tumor originates from the endometrium and its most common finding of imaging is a polypoid tumor occupying the uterine cavity. The authors herein present a case of 37-year-old female with a complaint of abnormal vaginal bleeding. At the first visit, transvaginal ultrasound and magnetic resonance imaging (MRI) showed a round mass with a diameter of one cm in the uterine wall. No malignant pathological finding was detected. The patient visited the authors again one year later, because of continuous bleeding. At that time, they found a polypoid tumor in the uterine cavity, which turned out to be adenosarcoma with sarcomatous overgrowth. The round mass in the uterus detected at first time seems to have been incipience of adenosarcoma. Prodromal sign of adenosarcoma has not been reported previously. PMID- 25118498 TI - Reference values for placental growth factor (PlGF) concentration and uterine artery doppler pulsatility index (PI) at 11-13(+6) weeks of gestation in the Polish population. AB - OBJECTIVES: The aim of the study was to determine placental growth factor (PIGF) concentration and uterine artery (UtA) Doppler pulsatility index (PI) at 11 13(+6) weeks of gestation in the Polish population. MATERIAL AND METHODS: A prospective study was performed in pregnant women who underwent routine ultrasound scan at 11-13(+6) weeks of gestation. All participants completed a questionnaire about their medical history demographics and current pregnancy. Mean arterial pressure (MAP) was calculated. Gestational age was confirmed by CRL and mean UtA PI was calculated. Blood samples were taken to measure beta HCG, PAPP-A and P/GF concentrations. RESULTS: Out of the 577 analyzed participants, 60 (10.4%) were found to have abnormal placentation disorders (20 -hypertensive disorders and 40-IUGR). The patients were subdivided into two groups, depending on pregnancy outcome: unaffected (n = 517) and affected (n = 60). The study did not confirm the anticipated correlation between maternal BMI and PIGF, but the concentration of PIGF was significantly increased in smokers. UtA PI values were not statistically significantly different depending on maternal age, BMI, method of conception, smoking or parity The study confirms that both, UtA PI and PIGF concentrations are CRL-dependent. Median MoM values for PIGF and UtA PI were obtained for each set of CRL measurements. Median PIGF MoM was decreased in pregnancies complicated by hypertensive disorders and IUGR as compared to the unaffected group. CONCLUSIONS: The established reference ranges for UtA PI and PIGF at 11-13(+6) weeks of gestation may be of clinical value in predicting placenta-associated diseases in early stages of pregnancy in the Polish population. PMID- 25118499 TI - The role of 401a>G polymorphism of methylenetetrahydrofolate dehydrogenase gene (MTHFD1) in fetal hypotrophy. AB - INTRODUCTION: Important role is attributed to genetic polymorphisms influencing enzymatic activity in folate metabolism. These inherited genetic variants may influence fetal growth and fetal hypotrophy development. The aim of the study was to investigate the connection of 401A>G polymorphism of methyleneterahydrofolate dehydrogenase gene (MTHFD1) with increased risk of fetal hypotrophy. MATERIAL AND METHODS: To the study group 120 women who delivered children with fetal hypotrophy and to the control group 120 healthy women were enrolled. Study group was divided into subgroups according to gestational age at delivery (52 patients < 37 weeks, 68 patients > or = 37 weeks) and to the neonatal weight (31 mothers of newborns with birth weight < 1500 g, 89 mothers of newborns with birth weight > or = 1500 g). The genetic analysis was performed with the use of PCR/RFLP method. RESULTS: We observed statistically higher occurrence of mutated 401A allele in hypotrophy group (401A: 27,1 vs. 18,8%, OR = 1,61, p = 0,02). At mothers who delivered hypotrophic children weighted more than 1500 g the presence of 401A allele was higher (28,7 vs. 18,8%, OR = 1,74, p = 0,01). Additionally in mothers who delivered hypotrophic children before 37 gestational week statistically higher frequency of 401A allele has been noted (31,7 vs. 18,8%, OR = 2,01, p = 0,007). CONCLUSIONS: Our results indicated that mutated 401A allele of MTHFD1 gene is essential risk factor of fetal hypotrophy in population of Polish women. Appropriate folate supplementation could be particularly essential in women carriers the genetic polymorphism influencing the folate metabolism. PMID- 25118500 TI - Comparison of maternal and fetal blood levels of caffeine and its metabolite. A pilot study. AB - OBJECTIVE: The aim of the study was to compare caffeine and paraxanthine concentrations in venous blood of pregnant women and in the umbilical cord blood of their newborns. MATERIALS AND METHODS: Pregnant women who gave birth at the Clinic of Obstetrics, Gynecology and Oncology 2nd Faculty of Medicine, Medical University of Warsaw were included in the study Caffeine and paraxanthine concentrations were analyzed in 30 samples of venous blood serum drawn from the women before delivery and 30 samples of umbilical cord blood serum of their newborns. Caffeine intake in the last 24 hours before delivery was estimated using a questionnaire. Statistical analysis employed a linear logistic regression model, Wilcoxon rank sum test and a non-parametric Spearman's rank correlation coefficient. RESULTS: No difference was found between caffeine concentration in maternal venous blood and neonatal umbilical cord blood. However; paraxanthine level in venous blood was higher than in umbilical cord blood (p = 0.04). CONCLUSIONS: Caffeine consumed by a pregnant woman passes through the placenta to the fetus freely. PMID- 25118501 TI - [Results of Doppler examinations in fetuses of mothers with early- and late-onset preeclampsia]. AB - OBJECTIVES: Comparison of fetal umbilical and middle cerebral artery flow between early- and late-onset preeclampsia. MATERIAL AND METHODS: Our study was conducted among 50 patients with preeclampsia in the third trimester of pregnancy and included 30 women with early-onset and 20 with late-onset disease. Early-onset preeclampsia (EOP) and late-onset preeclampsia (LOP) were defined as onset of the disease before and after 34 weeks of gestation, respectively Doppler examinations of the fetal umbilical and middle cerebral artery were performed in all patients. Pulsatility Index (PI) and cerebral-umbilical ratio (CUR) were measured each time. RESULTS: Mean value of the umbilical artery PI was significantly higher in fetuses of patients with EOP in comparison to LOF, whereas mean PI value in MCA was significantly lower in fetuses from the group with EOP than LOP The percentage of abnormal results of fetal Doppler examinations, both in the umbilical artery and middle cerebral artery was significantly higher in EOP than in LOP. The same tendency was observed for CUR. CONCLUSIONS: 1. Early-onset preeclampsia is characterized by significantly higher degree of placental insufficiency than late-onset disease. 2. The obtained results indicate a significant, pathological role of the placenta in early-onset preeclampsia. 3. Pathophysiological differences between early- and late-onset preeclampsia lead to different clinical approach to patients, depending on the type of the disease, including emphasis on Doppler examination in the early-onset preeclampsia. 4. The presence or absence of placental insufficiency in pregnancy complicated by preeclampsia seems to determine the clinical course of the disease, thus allowing for an alternative classification of the condition into placental and maternal preeclampsia. PMID- 25118502 TI - Retrograde diastolic blood flow in the aortic isthmus is not a simple marker of abnormal fetal outcome in pregnancy complicated by IUGR--a pilot study. AB - AIM: To evaluate the relation between retrograde diastolic blood flow in the aortic isthmus and adverse perinatal outcome in fetuses with IUGR. MATERIALS AND METHODS: The study included 33 fetuses with IUGR defined as the estimated fetal weight and abdominal circumference under the 10th percentile for a given gestational age. The Doppler examination of the blood flow in the aortic isthmus, umbilical artery umbilical vein, middle cerebral artery uterine arteries and ductus venosus was performed regularly The study population was further divided into two subgroups, depending on the aortic isthmus blood flow direction, i.e. with and without retrograde isthmic diastolic flow. Furthermore, the relation between Doppler blood flow parameters and determinants of the perinatal outcome was analyzed. The perinatal outcome was reported as adverse if any of the following occurred: umbilical cord blood pH < 7,2; 5-minute Apgar score < 7; respiratory distress syndrome, intraventricular hemorrhage (/ll/IV grade); necrotizing enterocolitis; sepsis; intrauterine or neonatal death. RESULTS: There was no statistically significant difference in the incidence of adverse perinatal outcome between the antegrade and retrograde isthmic blood flow groups. Moreover; the study showed no statistically significant relationship between the retrograde blood flow in the aortic isthmus and the prevalence of abnormal flow in the analyzed vessels. CONCLUSION: Retrograde diastolic blood flow in the aortic isthmus presents a low sensitivity and low predictive value in predicting the adverse perinatal outcome in pregnancies complicated with IUGR. PMID- 25118503 TI - Maternal serum amyloid A levels in pregnancies complicated with preterm prelabour rupture of membranes. AB - OBJECTIVE: The aim of the study was to investigate a possible association between maternal serum amyloid A levels (SAA) and maternal and fetal parameters in pregnancies complicated with preterm prelabor rupture of membranes (PPROM). MATERIAL AND METHODS: A total of 88 pregnant women (PPROM group, n = 44 and control group, n = 44) were included into this prospective case control study Serum blood samples for SAA were obtained from both groups within 1 h since the rupture of the membranes and before administration of any medicine. The samples were kept frozen at -70 degrees C until the analysis. The recorded risk factors were: age, gravidity parity delivery mode, gender; fetal birth weight, APGAR scores, white blood cell count, microCRRF neutrophil/lymphocyte ratio (NLR), and maternal serum SAA levels. RESULTS: Demographic characteristics showed no statistically significant differences between the groups (p > 0.05). The mode of delivery mode was cesarean section: 41% and 43.2% in the study and the control group, respectively and this difference was statistically significant between the groups (p < 0.05). Fetal parameters also showed statistically significant differences (p < 0.05). There was a statistically significant difference between the groups in terms of micro CRP NLR and SAA. SAA levels were higher in the PPROM group (p < 0.005). SAA levels at a cut-off 95.63 ng/ml. CONCLUSION: We are of the opinion that second trimester maternal serum SAA level may be a predictive marker for PPROM. However further studies with more participants are required. PMID- 25118504 TI - [Effects of metformin on the survival of the SKOV-3 ovarian cancer cell line and the expression of genes encoding enzymes involved in O-Glcnacylation]. AB - OBJECTIVES: The aim of the study was to evaluate the cytotoxic effect of metformin on the ovarian cancer cells SKOV-3 and analyze the impact of this compound on the expression of genes coding for O-GlcNAc cycling enzymes, i.e. O GlcNAc transferase (OGT) and -N-acetylglucosaminidase (OGA). MATERIALS AND METHODS: Viability and proliferation of control cells and cells treated with metformin were evaluated by MTT test and trypan blue staining. OGT and OGA mRNA expressions analysis was performed using real-time PCR method. RESULTS: A metformin concentration-dependent decrease of SKOV-3 cell viability was observed. The IC50 parameter for metformin cytotoxicity was 14 mM. The SKOV-3 cell doubling time was 45 hours. The cell population treated with 10 mM metformin did not double even after 72 hours. There was no significant difference in mRNA level of OGA between control cells and cells treated with metformin. The OGT mRNA level was significantly higher in cells treated with metforrhin for 24 hours as compared to the control cells. The increase of OGT mRNA was dependent on time of incubation. Cells treated with metformin for 48 hour showed higher expression of OGT than cells treated for 24 hours. CONCLUSION: Antiproliferative activity of metformin suggests that this compound may be considered as a candidate for potential chemotherapeutic agent. However taking into account its impact on the expression of O-GlcNAc transferase, further studies on the molecular mechanism of metformin action are necessary PMID- 25118505 TI - [Metformin in pregnancy]. AB - Metformin is an oral insulin-sensitizing anti-diabetic drug. Polycystic ovary syndrome (PCOS) and gestational diabetes (GDM) are both associated with insulin resistance and hyperinsulinemia. Metformin can bring potential benefits in pregnant women due to its favorable metabolic effect. Nevertheless, there is a possibility of adverse effects on the fetus as metformin crosses the placenta. In this review we discuss safety and indications for metformin administration in pregnancy. PMID- 25118506 TI - [Fetal hepatic artery flow assessment in prenatal diagnostics--a review of the literature]. AB - Standards of screening tests for the most frequent fetal chromosomal defects in modern non-invasive prenatal diagnostics provide sensitivity of about 93-96%, with the false positive rate of 2.5%. During the first trimester scan, routinely performed between 11 and 13+6 week of pregnancy the calculation of the risk for chromosomal aberrations is based on maternal age (MA), nuchal translucency (NT), levels of free beta human chorionic gonadotropin (free beta-hCG), pregnancy associated plasma protein A (PAPP-A) in maternal blood, as well as the parameters from extended ultrasound examination like evaluation of the nasal bone (NB), blood flow in ductus venosus (DV), visualization of the tricuspid valve with potential regurgitation (TR) or measurement of the frontomaxillary facial angle (FMFA). The 100% detection rate remains unachievable at present, despite constantly improving guidelines for specialists, quality of imaging, and advancement in ultrasound technology Therefore, several studies have been undertaken to establish the group of 'additional markers' of chromosomal defects which, when combined with basic markers of routine screening tests, might increase the detection rate and approach it to 100%. Results of recent studies imply that evaluation of blood flow in fetal hepatic artery performed during the first trimester scan may become a new additional marker for chromosomal defects. PMID- 25118507 TI - Complications of sub-urethral sling procedures. AB - Approximately one-third of the female population has been estimated to suffer from stress urinary incontinence. Surgical management of this disorder has been an area of ongoing innovation since the beginning of the 20th century. Better understanding of the underlying patomechanisms resulted in the invention of suburethral sling, that proved to be very effective in terms of the cure rates. The introduction of sling techniques also caused a considerable reduction of the rates of intra- and postoperative complications of incontinence treatment. Unfortunately modern anti-incontinence surgery continues to be associated with a high risk of both, perioperative morbidity and long-term adverse outcomes, even with the recently introduced single-incision techniques. The article focuses on intra- and postoperative complications of sling techniques in anti-incontinence surgery. Both, common and rare adverse outcomes are widely discussed. PMID- 25118509 TI - [Krukenberg tumor--a multidisciplinary approach--a case report]. AB - Metastatic lesions within the ovary constitute a serious diagnostic problem in daily practice. We present an interesting case of Krukenberg tumor in a woman 13 years after partial gastrectomy due to stomach cancer. Our case confirms that every woman with history of cancer should remain under gynecological control. It is important due to a high risk of metastatic changes localized in the ovaries, regardless of the time elapsed since the diagnosis of the primary tumor PMID- 25118508 TI - Prenatal diagnosis of craniosynostosis (compound Saethre-Chotzen syndrome phenotype) caused by a de novo complex chromosomal rearrangement (1; 4; 7) with a microdeletion of 7p21.3-7p15.3, including TWIST1 gene--a case report. AB - Craniosynostosis (a premature fusion of the cranial sutures) occurs with a frequency of 1 in 2100-2500 births and in over 40% cases is caused by known genetic factors--either single gene mutations or chromosomal rearrangements. Cases caused by complex chromosomal abnormalities are uncommon and likely associated with compound phenotype. Saethre-Chotzen syndrome (SCS) [#101400] is caused by TWIST1 gene haploinsufficiency. Its phenotype includes uni- or bicoronal synostosis, short stature, facial dysmorphism and variable anomalies of the hands and feet. Due to its poor sonographic manifestation a prenatal diagnosis of SCS is challenging. We report a case of a prenatally detected craniosynostosis (compound Saethre-Chotzen syndrome phenotype) caused by a de novo complex chromosomal rearrangement (1; 4; 7) with a microdeletion of 7p21.3 7p15.3, including TWIST1 gene. PMID- 25118510 TI - [Assisted reproductive medicine in Poland, 2011--SPiN PTG report]. AB - AIM: The aim of this report is to present data concerning results and complications related to infertility treatment using assisted reproductive technology (ART) and insemination (IUI) in Poland in 2011. MATERIALS AND METHODS: The report was prepared by the Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG), based on individual data provided by fertility clinics in Poland. Reporting was voluntary and the provided data was not subject to external control. The report presents the availability and the structure of infertility treatment services, the number of procedures performed, their effectiveness and the most common complications. MAIN RESULTS: In 2013, 33 Polish fertility clinics provided information to the SPiN PTG report, presenting data from the year 2011. The total number of reported treatment cycles using ART was 15,340 (incl. 10,011 IVF/ICSI procedures) and 15,627 IUI procedures. The rate of clinical pregnancies in terms of a cycle was 34.2% in case of IVF/ ICSI procedures and 13.4% in case of IUI. The prevalence of multiple births was 20.2% and 8.3% respectively in case of IVF/ICSI and IUI methods. The most frequent complication in the course of treatment using ART was ovarian hyperstimulation syndrome (OHSS). CONCLUSION: The SPiN PTG report allows to find out the average effectiveness and safety of assisted reproduction technologies and is currently the only proof of responsibility and due diligence of fertility centres in Poland. However due to the lack of a central register of fertility clinics, facultative participation in the report as well as incomplete information on pregnancy and delivery the collected data does not reflect the full spectrum of the Polish reproductive medicine. PMID- 25118511 TI - [Recommendations of the Polish Gynecological Society concerning application of GINEintima products in gynecology]. PMID- 25118512 TI - An examination of assessment arrangements and service use for older people in receipt of care management. AB - With anticipated greater demand for formal care services globally, this article examines the sociodemographic and health characteristics of frail older people in receipt of community support. Data were collected from audits of case files of older people receiving care management at two time points during which two government policy initiatives were implemented to promote greater standardization in health and social care provision for older people in England. Findings at Time 2 revealed that there were higher levels of physical and mental impairment and more health care assessments undertaken. There was a slight decrease in home care receipt but a marginal increase of more intensive home care provision. Service users living with a carer were less likely to receive home care but more likely to receive respite care or day care than those living alone. The policy goal of widening access to specialist health and social care services for older people with mental health problems was achieved. Guidance that focused eligibility criteria on the identification of older people with complex needs required the availability of appropriate support and services. Irrespective of policy initiatives, the sociodemographic characteristics of older people and the availability of informal support are principal determinants of service provision. PMID- 25118513 TI - Increased longevity in HIV: caring for older HIV-infected adults. AB - The demographics of the HIV-infected population in the United States have shifted in a way that few would have predicted 30 years ago when the tide of sick and dying patients largely consisted of young men. Effective ART has allowed those infected to live long, productive lives and to grow old with their disease. With the increase in life expectancy afforded by HIV treatment, the cause of death among HIV-infected individuals is far more likely to be from an HIV-associated non-AIDS condition. Nonetheless, HIV seems to accelerate the aging process, and care providers involved in the treatment of older patients with HIV need to be aware that their patients are at increased risk of developing various common disorders, compared to uninfected same-age patients. Clinicians need to remain vigilant to the possibility of a new diagnosis of HIV among their older patients. Awareness of current or distant risk, frank discussions of sexual practices, and willingness to offer routine testing are crucial to making this diagnosis, with the recognition that longevity for patients with HIV is directly linked to how soon they enter care. HIV infection adds another challenge to the management of older patients; geriatricians and HIV specialists need to coordinate their efforts to provide patients with comprehensive multidisciplinary care. Older patients with HIV also have social and psychological needs that extend beyond the medical office. Maintaining independence, acknowledging limitations, reducing risk of adverse events such as falls or medication errors, and supporting self acceptance and awareness are only a few of the many areas where care providers outside the medical office can be important for patients' ongoing well-being. Accessing family support, community outreach, church affiliation, or other outpatient support networks can be useful for patients. The remarkable change in prognosis brought about by effective ART in the mid-1990s has meant that HIV is now, for many, a manageable chronic illness. Clinicians and other care providers are changing their approach and goals of care as patients with HIV grow old. PMID- 25118514 TI - Constipation in the long-term care setting. PMID- 25118516 TI - Yet another new era? PMID- 25118517 TI - Medical consultations for dental patients in 2014. PMID- 25118518 TI - Focus on: impressions. PMID- 25118519 TI - Light coaxes stem cells to repair teeth. PMID- 25118520 TI - Majority of dental professionals believe implant guidelines necessary for optimal patient outcomes. PMID- 25118521 TI - High-need dental clinic coming to St. Louis. PMID- 25118522 TI - Dental schools name new deans. PMID- 25118524 TI - States' and communities' fluoridation efforts honored. PMID- 25118523 TI - "Pass that bottle to me!". Red wine's cavity-fighting benefits are once again verified. PMID- 25118525 TI - Orthodontic forced eruption: a team approach in aesthetic treatment. PMID- 25118526 TI - Endodontic canal preparation: innovations in glide path management and shaping canals. PMID- 25118527 TI - Preformed design bridging concept: a case report. PMID- 25118528 TI - A multipurpose temporary tooth replacement: aesthetic tooth-borne alternative used prior to an implant. PMID- 25118529 TI - Simplifying cementation of high-strength restorations: using an improved resin modified glass ionomer cement. PMID- 25118530 TI - Placement of a modified subperiosteal implant: a clinical solution to help those with no bone. PMID- 25118531 TI - Two-stage mini dental implants: is it time to join the party? PMID- 25118532 TI - A multidisciplinary team approach improves outcomes: treatment of an aesthetically conscious patient with gingival recession. PMID- 25118533 TI - Neurosurgery in South Africa. PMID- 25118535 TI - Physician, heal thyself: creative writing as a tool for self-care and enhancing care of others. PMID- 25118534 TI - Hereditary haemorrhagic telangiectasia in North African and sub-Saharan patients. PMID- 25118536 TI - The neglected triple disease burden and interaction of helminths, HIV and tuberculosis: an opportunity for integrated action in South Africa. PMID- 25118537 TI - Palliative care: definition of euthanasia. PMID- 25118538 TI - Prof. McQuoid-Mason responds. PMID- 25118539 TI - Palliative care: preventing misconceptions. PMID- 25118540 TI - Prof. McQuoid-Mason responds. PMID- 25118541 TI - WHIDMT: Rossouw and Howard blatantly miss the point. PMID- 25118543 TI - E Cape health officials nearly turn TB victims into cash cows. PMID- 25118542 TI - Community service doctors 'slaves to the state'--court challenge. PMID- 25118544 TI - Quack remedy cast--'we were pawns, not told, didn't know, won't say, don't care'. PMID- 25118545 TI - Ivan James Nurick. PMID- 25118546 TI - Hessel Utian. PMID- 25118547 TI - Diagnosis and management of Pompe disease. AB - Pompe disease (PD) is an autosomal-recessively inherited neuromuscular disease that, if not diagnosed and treated early, can be fatal. It can present from early infancy into adulthood. Due to the lack of acid alpha-glucosidase, there is progressive intracellular accumulation of glycogen. The severity of the disease is determined by age of onset, organ involvement including the degree of severity of muscle involvement, as well as rate of progression. PD is classified into two groups: infantile and late-onset, each having two subgroups. The need for two tests performed by separate methods (screening and confirmatory) is outlined. It is imperative to try to reduce the time to diagnosis and to recognise the possibilities of false-positive results. A multidisciplinary team approach to treatment of affected patients is optimum with, as team leader, a physician who has experience in managing this rare disorder. In this article, we present a brief overview of the disease and provide guidelines for diagnosis and management of this condition in South Africa. PMID- 25118548 TI - The Teddy Bear Clinic Constitutional Court case: sexual conduct between adolescent consenting children aged under 16 years decriminalised and a moratorium on the reporting duties of doctors and others. AB - The Constitutional Court in the Teddy Bear Clinic appeal case held that the sections of the Sexual Offences Act that impose criminal liability for sexual offences on adolescent children under 16 years of age are invalid. The invalidity was suspended for 18 months to allow Parliament to correct the Act's defects. A moratorium was imposed on all investigations into, arrests in, prosecutions in, and criminal and ancillary proceedings regarding such section 15 and 16 offences. This includes the duty to report consensual sexual conduct between children under 16 years of age in terms of section 54 of the Act--pending Parliament's correction. However, it is submitted that the 'best interests of the child' principle in the Children's Act and the Constitution should guide all obligatory reporting situations involving sexual and other conduct of children, irrespective of whether they are adolescents under 16 years old or between 16 and 17 years old. PMID- 25118549 TI - The risks of gastrointestinal injury due to ingested magnetic beads. AB - Accidental ingestion of foreign bodies is a common problem in children. Magnetic bead toys are hazardous, having potentially lethal consequences if ingested. These magnets conglomerate in different segments of bowel, causing pressure necrosis, perforation and/or fistula formation anywhere along the gastrointestinal tract. A clinical diagnostic pitfall is that the appearance on the initial abdominal radiograph may be misinterpreted by the uninitiated as a single metallic object without any intervening intestinal wall. Symptoms do not occur until complications have developed, and even then, unless magnet ingestion is suspected, treatment may initially be mistakenly expectant, as with any other foreign body. After observing a case of multiple magnet ingestion that led to the rapid onset of small-bowel inter-loop fistulas and peritonitis, we attempted to reproduce the likely sequence of events in a laboratory setting using fresh, post mortem porcine bowel as an animal model and placing magnetic toy beads within the bowel lumen. Pressure-induced perforation appeared extremely rapidly, replicating the operative findings in two of our cases. We propose that if magnet ingestion is suspected, early endoscopic or surgical retrieval is mandatory. Appropriate, rapid surgical intervention is indicated. Laparoscopy offers a minimally invasive therapeutic option. PMID- 25118550 TI - The safety of osteoporosis medication. AB - Osteoporosis is a common, costly and serious disease, which is still too often regarded as an inevitable part of the normal ageing process and therefore sub optimally treated, especially in the elderly--in fact, only two out of every 10 patients who sustain a hip fracture receive any form of assessment or prophylactic therapy for osteoporosis. One out of five patients die within 1 year after a hip fracture, and < 50% are capable of leading an independent life. Yet very effective anti-fracture therapy, capable of reducing fracture risk by 35 - 60%, is available. A number of publications have recently questioned the safety of drugs routinely used to treat patients with osteoporosis. This paper attempts to put the situation into perspective and expresses the National Osteoporosis Foundation of South Africa's view on the safety of these drugs. Their efficacy in preventing skeletal fractures and their cost-effectiveness are not addressed in any detail. The paper emphasises the fact that all osteoporosis medications have side-effects, some of which are potentially life-threatening. PMID- 25118551 TI - Acute intermittent porphyria presenting as progressive muscular atrophy in a young black man. AB - Acute intermittent porphyria, the most common porphyria affecting the nervous system, typically presents with neurovisceral crises followed by a motor neuropathy. We describe a 23-year-old black South African man presenting with a progressive stuttering, lower motor neuron syndrome developing over months. He had not experienced pain or neuropsychiatric symptoms. One year after symptom onset he was bed-bound with a flaccid quadriparesis. There was marked amyotrophy, but without fasciculations. Sensation was intact apart from a hypo-aesthetic patch over the thigh. Electrophysiological investigations showed an active motor axonopathy. Urinary porphyrins, delta-aminolaevulinic acid and porphobilinogen were elevated. Mutation analysis revealed the c445C>T (R149X) mutation in the porphobilinogen deaminase gene. The patient responded dramatically to haem arginate and could walk with assistance 2 weeks later. We identified the first molecularly confirmed acute intermittent porphyria in a black South African. The clinical presentation mimicked a progressive lower motor neuron syndrome. PMID- 25118552 TI - The neurological manifestations of the acute porphyrias. PMID- 25118553 TI - Increased visibility and discoverability of South African health-related research. PMID- 25118554 TI - High prevalence of cisplatin-induced ototoxicity in Cape Town, South Africa. AB - BACKGROUND: Cisplatin is administered as the first-line treatment of soft-tissue cancers. It has a reported cure rate of up to 85%, but is associated with a high incidence of ototoxicity, characterised by irreversible bilateral hearing loss and affecting 23 - 50% of adults who receive the drug. OBJECTIVES: To determine the incidence of cisplatin-induced ototoxicity at Groote Schuur Hospital (GSH), Cape Town, South Africa. METHODS: retrospective cross-sectional study of cisplatin-receiving cancer patients attending GSH between January 2006 and August 2011. RESULTS: A total of 377 patients were recorded as receiving cisplatin therapy during the study period. A 300% increase in new cisplatin-receiving patients receiving audiological monitoring was observed between 2006 and 2010. However, only patients with all clinical data as well as baseline and follow-up audiometric analyses were investigated. One hundred and seven such patients were identified, 55.1% of whom developed cisplatin-induced ototoxicity while receiving high-dose (> or = 60 mg/m2) cisplatin treatment. Higher cumulative cisplatin dosages were associated with development of significant hearing loss (p = 0.027). The odds of developing cisplatin-induced hearing loss were elevated for patients with head and neck tumours and lymphoma (p = 0.0465 and p = 0.0563, respectively) and were significantly lower for those with reproductive cancers (p = 0.0371). CONCLUSION: Comprehensive audiological monitoring should be available for every patient during cisplatin treatment to minimise the development of disabling hearing loss. PMID- 25118555 TI - Angiotensin converting enzyme inhibitors v. angiotensin receptor blockers in the management of hypertension: a funder's perspective. AB - BACKGROUND: Hypertension poses a huge financial risk to any funder/medical aid, including the risk-mitigating strategies provided by the managed care organisations that are required to manage patients with hypertension. The South African Hypertension Guideline states that the choice of therapy--an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB)- should be based on cost and tolerability. OBJECTIVE: To assess the costs of ACEIs v. ARBs in the management of hypertensive patients and the prevention of cardiovascular complications for a private medical aid scheme in South Africa. METHOD: A Phase IV observational, retrospective cohort study of over 480 000 beneficiaries between 2010 and 2011 was undertaken. Hypertensive patients were identified by their chronic medication authorisation and were categorised into three groups: ACEI, ARB and combined groups. A cost-benefit analysis was performed on the claims data, comparing the input costs in rand against the downstream costs using analysis of variance. RESULTS: Data from 28 165 patients were included in the study. Based on the health economic analysis that was performed, there was no statistically significant difference in the input costs between the ACEI and the ARB groups. However, a statistically significant reduction in the downstream costs was observed in the ACEI group v. the ARB and combined groups (p < 0.0001). CONCLUSION: It is more cost beneficial to treat chronic hypertensive patients with an ACEI than ARBs in preventing cardiovascular related complications. It is recommended that managed care companies continue recommending ACEIs rather than ARBs in the treatment of hypertensive patients. PMID- 25118556 TI - Mammographic screening for breast cancer in a resource-restricted environment. AB - BACKGROUND: Mammographic screening is carried out at public sector hospitals as part of clinical practice. OBJECTIVE: We report the experience of such screening at Tygerberg Academic Hospital (TBAH), a tertiary referral hospital in the Western Cape Province, South Africa. METHODS: All mammograms performed between 2003 and 2012 at TBAH were analysed regarding patient demographics, clinical data, indication and outcome according to the American College of Radiology Breast Imaging Reporting and Data System (BIRADS). Screening mammography was offered to patients > 40 years of age and mammograms were read by experienced breast surgeons. Patients with BIRADS 3 and 4 lesions were recalled for short term follow-up, further imaging or tissue acquisition. Patients with BIRADS 5 lesions were recalled for tissue acquisition. Further imaging, method of tissue acquisition, histology results and use of neo-adjuvant therapy were also recorded. RESULTS: Of 16 105 mammograms, 3 774 (23.4%) were carried out for screening purposes. The median age of patients undergoing screening was 54 years. Of 407 women with mammograms that were reported as BIRADS 3 - 5 (10.8% of screening mammograms), 187 (46% of recalled women) went on to have further imaging only. Tissue was acquired in 175 patients (43% of recalled women), comprising a biopsy rate of 4.6% of the total series. The malignancy rate in cases in which tissue acquisition was done was 25%. Forty-three breast cancers were diagnosed (11.4/1 000 examinations). Of the cancers, nine (31%) were ductal carcinomas in situ. Of 20 invasive cancers, nine (45%) were < 10 mm in size. Of the invasive cancers, 40% were node-positive. CONCLUSIONS: The cancer diagnosis rate indicates a high breast cancer load in an urbanised population. PMID- 25118557 TI - Results of a pilot programme of mammographic breast cancer screening in the Western Cape. AB - BACKGROUND: Mammographic screening programmes are now established in developing countries. We present an analysis of the first screening programme in sub-Saharan Africa. METHODS: Women aged > or = 40 years were identified at three primary healthcare centres in the Western Cape Province, South Africa, and after giving informed consent underwent mammography at a mobile unit. After a single reading, patients with American College of Radiology Breast Imaging Reporting and Data System (BIRADS) 3 - 5 lesions were referred to a tertiary centre for further management. RESULTS: Between 1 February 2011 and 31 August 2012, 2 712 screening mammograms were performed. A total of 261 screening mammograms were reported as BIRADS 3 - 5 (recall rate 9.6%). Upon review of the 250 available screening mammograms, 58 (23%) were rated benign or no abnormalities (BIRADS 1 and 2) and no further action was taken. In 32 women, tissue was acquired (biopsy rate for the series 1.2%); 10 cancers were diagnosed (biopsy malignancy rate 31%). For the entire series of 2 712 screening mammograms, the cancer diagnosis rate was 3.7/1 000 examinations. Of 10 cancers diagnosed at screening, 5 were TNM clinical stage 0, 2 stage I and 3 stage II. CONCLUSIONS: The low cancer detection rate achieved, and the technical and multiple administrative problems experienced do not justify installation of a screening programme using the model utilised in this series. PMID- 25118558 TI - Community v. non-community assault among adults in Khayelitsha, Western Cape, South Africa: a case count and comparison of injury severity. AB - BACKGROUND: Community assault (CA) or vigilantism is widespread in the township of Khayelitsha, Cape Town, South Africa (SA). Anecdotal evidence suggests that victims of CA are worse off than other assault cases. However, scientific data on the rate and severity of CA cases are lacking for SA. OBJECTIVES: To contribute to CA prevention and management strategies by estimating the rate of CA among adults in Khayelitsha and comparing the injury severity and survival probability between cases of CA and other assault (non-CA) cases. METHODS: We studied four healthcare centres in Khayelitsha during July - December 2012. A consecutive case series was conducted to capture all CA cases during this period. A retrospective folder review was performed on all cases of CA and on a control group of non-CA cases to compare injury severity and estimate survival probability. RESULTS: A total of 148 adult cases of CA occurred (case rate 1.1/1 000 person-years) over the study period. The Injury Severity Scores (ISSs) in the CA group were significantly higher than in the non-CA group (p < 0.001), with a median (interquartile range) ISS of 3 (2 - 6) in CA cases v. 1 (1 - 2) in non-CA cases. Comparison between the CA v. non-CA groups showed that a Glasgow Coma Scale < 15 (20.1% v. 5.4%, respectively), referral to the tertiary hospital (33.8% v. 22.6%, respectively), and crush syndrome (25.7% v. 0.0%, respectively) were all more common in CA cases. Survival probabilities were similar in both groups (CA v. non CA 99.2% v. 99.3%, respectively). CONCLUSION: The rate of CA among adults in Khayelitsha is high, and the severity of injuries sustained by CA victims is substantially higher than in other assault cases. PMID- 25118559 TI - Self-induction of abortion among women accessing second-trimester abortion services in the public sector, Western Cape Province, South Africa: an exploratory study. AB - BACKGROUND: Despite South Africa's liberal abortion law permitting abortion on request in the first trimester and under restricted conditions for second trimester pregnancies, the practice of unsafe self-induced abortion persists. However, the prevalence of this practice, the methods used and the reasons behind it are relatively under-researched. As part of a larger study seeking to improve abortion services in the Western Cape Province, we explored reports of prior attempts to self-induce abortion among women undergoing legal second-trimester abortion. OBJECTIVES: To describe the prevalence and methods of and factors related to unsuccessful attempts at self-induction of abortion by women presenting without complications and seeking second-trimester abortion at public health facilities in the Western Cape. METHODS: In a cross-sectional study from April to August 2010, 194 consenting women undergoing second-trimester abortion were interviewed by trained fieldworkers using structured questionnaires at four public sector facilities near Cape Town. RESULTS: Thirty-four women (17.5%; 95% confidence interval 12.7 - 23.4) reported an unsuccessful attempt to self-induce abortion during the current pregnancy before going to a facility for second trimester abortion. No factors were significantly associated with self-induction, but a relatively high proportion of this small sample were unemployed and spoke an indigenous African language at home. A readily available herbal product called Stametta was most commonly used; other methods included taking tablets bought from unlicensed providers and using other herbal remedies. No use of physical methods was reported. CONCLUSIONS: The prevalence of unsafe self-induction of abortion is relatively high in the Western Cape. Efforts to inform women in the community about the availability of free services in the public sector and to educate them about the dangers of self-induction and unsafe providers should be strengthened to help address this public health issue. PMID- 25118560 TI - Clinicians ignore best practice guidelines: prospective audit of cardiac injury marker ordering in patients with chest pain. AB - BACKGROUND: Chest pain is a frequent presenting symptom and is a diagnostic challenge. Recent recommendations state that high-sensitivity cardiac troponin assays are the only biochemical test required in the diagnosis of acute coronary syndrome (ACS) and that other biomarkers such as myoglobin or creatine kinase (CK)-MB isoform are not indicated. OBJECTIVE: To establish whether clinician ordering in the setting of suspected ACS was in keeping with recent recommendations. METHODS: A prospective audit was undertaken of all requests for cardiac troponin I (cTnI) and CK-MB received at a large tertiary hospital in Durban, South Africa, during a 20-day period in December 2012. RESULTS: A total of 193 cardiac marker requests were received: 12 (6.2%) requests were for cTnI alone; 8 (4.1%) were for CK-MB alone; and the remaining 173 (89.7%) were for both cTnI and CK-MB. Therefore, a total of 181 (93.8%) incorrect requests were received during this period. A total of 103 (53.4%) patients had values below the cut-off point of 40 ng/l for cTnI, i.e. ACS was ruled out. Of these, 15 had CK-MB values above the reference interval. A total of 12 (6.2%) patients had cTnI values > 500 ng/l, i.e. ACS was ruled in; 33.3% of this group had normal CK-MB values. CONCLUSION: Ordering patterns in the setting of ACS did not reflect current recommendations and were wasteful and potentially dangerous. PMID- 25118561 TI - Hepatitis B and HIV co-infection in pregnant women: indication for routine antenatal hepatitis B virus screening in a high HIV prevalence setting. AB - BACKGROUND: Sub-Saharan Africa is endemic for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections. HBV/HIV co-infection in women of reproductive age is of clinical and public health importance because these women constitute a significant reservoir for horizontal and perinatal HBV transmission. Childhood HBV vaccination from 6 weeks of age protects most children against chronic HBV infection. However, infants born to HBV/HIV co-infected women are more likely to be infected perinatally, with an increased risk of chronic hepatitis, than infants born to HBV mono-infected women. OBJECTIVES: The aim of our study was to establish the prevalence of HBV infection and HBV/HIV co infection in pregnant women in KwaZulu-Natal, South Africa, to inform antenatal HBV screening and childhood immunisation policies in South Africa. METHODS: Stored plasma specimens obtained from 570 pregnant women were tested for hepatitis B surface antigen (HBsAg) and HBV infectivity, as characterised by the presence of hepatitis B e antigen (HBeAg) and/or HBV DNA load. RESULTS: The antenatal HIV prevalence and HBsAg prevalence in this study were 41.6% and 5.3% (95% confidence interval (CI) 3.4 - 7.1), respectively. Overall, 3.1% (95% CI 1.7 - 4.6) of pregnant women were HBV/HIV co-infected, with HBeAg positivity and the HBV DNA load being significantly higher in co-infected women. CONCLUSION: We report a 5.3% HBV prevalence and a 3.1% HBV/HIV co-infection prevalence in pregnant women from this HIV-endemic region. Routine antenatal HBV screening will allow early identification of neonates who require HBV active-passive immunoprophylaxis at birth. This strategy, together with antenatal antiretrovirals, will reduce the risk of perinatal HBV transmission, especially in high-risk HBV/ HIV co-infected pregnant women. PMID- 25118562 TI - Transition from child- to adult-orientated care for children with long-term health conditions: a process, not an event. AB - Long-term health conditions in childhood include both congenital conditions and acquired diseases. Children with long-term health conditions face issues and potential secondary problems that are different from those of adults with chronic diseases. Transition to adult-orientated care for such children and adolescents is a major challenge. Transition needs to be prepared for and planned. A variety of possible transition models exists, depending on circumstances. PMID- 25118563 TI - Aedes aegypti larvicide from the ethanolic extract of Piper nigrum black peppercorns. AB - Due to unavailability of a vaccine and a specific cure to dengue, the focus nowadays is to develop an effective vector control method against the female Aedes aegypti mosquito. This study aims to determine the larvicidal fractions from Piper nigrum ethanolic extracts (PnPcmE) and to elucidate the identity of the bioactive compounds that comprise these larvicidal fractions. Larvicidal assay was performed by subjecting 3rd to 4th A. aegypti instar larvae to PnPcmE of P. nigrum. The PnPcmE exhibited potential larvicidal activity having an LC50 of 7.1246 +/- 0.1304 ppm (mean +/- Std error). Normal phase vacuum liquid chromatography of the PnPcmE was employed which resulted in five fractions, two of which showed larvicidal activity. The most active of the PnPcmE fractions is PnPcmE-1A, with an LC50 and LC90 of 1.7101 +/- 0.0491 ppm and 3.7078 ppm, respectively. Subsequent purification of PnPcmE-1A allowed the identification of the larvicidal compound as oleic acid. PMID- 25118564 TI - The relationships between adult attachment, theoretical orientation, and therapist-reported alliance quality among licensed psychologists. AB - OBJECTIVE: Attachment anxiety has been depicted as an undesirable therapist characteristic based on findings that preoccupied therapists, relative to those with other attachment styles, report more ruptures in the therapeutic alliance. What has not been considered, however, is the extent to which attachment dynamics are related to theoretical orientations and how attachment styles and theoretical orientations combine to predict therapists' perceptions of the quality of their alliances. METHOD: The present surveyed 290 licensed psychologists nationally. RESULTS: Results revealed that even within a sample of primarily secure psychologists, higher 15 levels of attachment anxiety correlated positively with the endorsement of psychodynamic orientations, and negatively with the endorsement of cognitive-behavioral orientations and self-reported alliance quality. Endorsement of cognitive-behavioral orientations, in turn, correlated positively with therapist-reported alliance quality. CONCLUSION: The results are discussed in terms of the extent to which attachment dimensions should be considered in therapists' understandings of their therapeutic alliances. PMID- 25118565 TI - Efficient planar perovskite solar cells based on 1.8 eV band gap CH3NH3PbI2Br nanosheets via thermal decomposition. AB - Hybrid organometallic halide perovskite CH3NH3PbI2Br (or MAPbI2Br) nanosheets with a 1.8 eV band gap were prepared via a thermal decomposition process from a precursor containing PbI2, MABr, and MACl. The planar solar cell based on the compact layer of MAPbI2Br nanosheets exhibited 10% efficiency and a single wavelength conversion efficiency of up to 86%. The crystal phase, optical absorption, film morphology, and thermogravimetric analysis studies indicate that the thermal decomposition process strongly depends on the composition of precursors. We find that MACl functions as a glue or soft template to control the initial formation of a solid solution with the main MAPbI2Br precursor components (i.e., PbI2 and MABr). The subsequent thermal decomposition process controls the morphology/surface coverage of perovskite films on the planar substrate and strongly affects the device characteristics. PMID- 25118566 TI - Erectile dysfunction in psoriasis patients. AB - BACKGROUND: An association between psoriasis and sexual dysfunction has been explored. However, not much is known about the factors behind erectile dysfunction in these patients. OBJECTIVES: To compare the prevalence and the severity of erectile dysfunction in patients with and without psoriasis and to determine potential associations between erectile dysfunction and psoriasis patients' characteristics. MATERIALS & METHODS: An observational cross-sectional study was conducted at two tertiary hospital-based Dermatology departments. Consecutive adult men with psoriasis or other skin conditions were recruited. Data were collected using an anonymous, self-completed, designed questionnaire, which included the Dermatology Life Quality Index and the 5-item version of the International Index of Erectile Function. RESULTS: A total of 135 psoriasis patients and 201 controls were included. Psoriasis patients had a higher prevalence of erectile dysfunction than controls (61.5% vs 43.8%, p = 0.001), and an increased risk of more severe forms of erectile dysfunction. Dermatology Life Quality Index, genital psoriasis and psoriasis duration were not associated with the presence of erectile dysfunction. In multivariate logistic regression, psoriasis and diabetes were found to be independent risk factors for erectile dysfunction with estimated odds ratios of 2.28 (CI 95%, 1.40-3.27) and 3.49 (CI 95%, 1.40-8.66), respectively. CONCLUSION: This study suggests psoriasis as a risk factor for erectile dysfunction. Atherosclerosis is a plausible connecting link, adding up to the already acknowledged effect of psychological factors in these patients. From a clinical standpoint, because erectile dysfunction may precede overt cardiovascular disease, it can be used as a precocious marker of cardiovascular risk in psoriatic men. PMID- 25118567 TI - Selective interception of gelsolin amyloidogenic stretch results in conformationally distinct aggregates with reduced toxicity. AB - The pathogenesis of protein misfolding diseases is attributed to the cytotoxicity caused by amyloidogenic prefibrillar aggregates, rather than mature fibrils. The presence of one or more amyloidogenic stretches in different proteins has been proven critical for initiating fibril formation. In the present study, we show that two natural compounds, curcumin and emetine, bind tightly (Kd < 1.6 MUM) to the core amyloidogenic stretch (182-192) of gelsolin (AGel). Binding happens in different structural orientations, distinctly modulating the amyloidogenic pathway of AGel. While AGel alone undergoes sigmoidal transition to thioflavin T (ThT)-responsive fibrillar aggregates with clear lag phase, the presence of curcumin or emetine abolishes the lag phase and produces starkly different, noncytotoxic end products. Atomic force microscopy revealed that while curcumin augments fibril formation, emetine arrests it at an intermediate aggregated stage with no fibrillar morphology. FTIR spectroscopy, dynamic light scattering, and ANS fluorescence experiments also suggest that these two species are distinct. Curcumin and emetine also differentially affect the preformed amyloids with the former thickening the fibrils and the latter releasing reclusive oligomers. MD simulations further provided mechanistic insights of differential interaction by the two compounds modulating amyloid formation. The results were also confirmed on the disease-associated amyloidogenic fragment of gelsolin (fAGel). Thus, our findings suggest that targeting amyloidogenic stretches in proteins could be useful in designing novel molecules against protein misfolding diseases. PMID- 25118569 TI - Microbial community response to chlorine conversion in a chloraminated drinking water distribution system. AB - Temporary conversion to chlorine (i.e., "chlorine burn") is a common approach to controlling nitrification in chloraminated drinking water distribution systems, yet its effectiveness and mode(s) of action are not fully understood. This study characterized occurrence of nitrifying populations before, during and after a chlorine burn at 46 sites in a chloraminated distribution system with varying pipe materials and levels of observed nitrification. Quantitative polymerase chain reaction analysis of gene markers present in nitrifying populations indicated higher frequency of detection of ammonia oxidizing bacteria (AOB) (72% of samples) relative to ammonia oxidizing archaea (AOA) (28% of samples). Nitrospira nitrite oxidizing bacteria (NOB) were detected at 45% of samples, while presence of Nitrobacter NOB could not be confirmed at any of the samples. During the chlorine burn, the numbers of AOA, AOB, and Nitrospira greatly reduced (i.e., 0.8-2.4 log). However, rapid and continued regrowth of AOB and Nitrospira were observed along with nitrite production in the bulk water within four months after the chlorine burn, and nitrification outbreaks appeared to worsen 6-12 months later, even after adopting a twice annual burn program. Although high throughput sequencing of 16S rRNA genes revealed a distinct community shift and higher diversity index during the chlorine burn, it steadily returned towards a condition more similar to pre-burn than burn stage. Significant factors associated with nitrifier and microbial community composition included water age and sampling location type, but not pipe material. Overall, these results indicate that there is limited long-term effect of chlorine burns on nitrifying populations and the broader microbial community. PMID- 25118568 TI - Early cortical thickness change after mild traumatic brain injury following motor vehicle collision. AB - In a motor vehicle collision (MVC), survivors often receive mild traumatic brain injuries (mTBI). Although there have been some reports of early white matter changes after an mTBI, much less is known about early cortical structural changes. To investigate early cortical changes within a few days after an MVC, we compared cortical thickness of mTBI survivors with non-mTBI survivors, then reexamined cortical thickness in the same survivors 3 months later. MVC survivors were categorized as mTBI or non-mTBI based on concussive symptoms documented in emergency departments (EDs). Cortical thickness was measured from MRI images using FreeSurfer within a few days and again at 3 months after MVC. Post traumatic stress symptoms and physical conditions were also assessed. Compared with the non-mTBI group (n = 23), the mTBI group (n = 21) had thicker cortex in the left rostral middle frontal (rMFG) and right precuneus gyri, but thinner cortex in the left posterior middle temporal gyrus at 7.2 +/- 3.1 days after MVC. After 3 months, cortical thickness had decreased in left rMFG in the mTBI group but not in the non-mTBI group. The cortical thickness of the right precuneus region in the initial scans was positively correlated with acute traumatic stress symptoms for all survivors and with the number of reduced activity days for mTBI survivors who completed the follow-up. The preliminary results suggest that alterations in cortical thickness may occur at an early stage of mTBI and that frontal cortex structure may change dynamically over the initial 3 months after mTBI. PMID- 25118571 TI - Rare earth elements supply restrictions: market failures, not scarcity, hamper their current use in high-tech applications. PMID- 25118573 TI - Cochlear Meniere's Disease in Association With a High Jugular Bulb. PMID- 25118574 TI - A Case of Rotational Vertebral Artery Syndrome. PMID- 25118572 TI - Development and evaluation of a truncated recombinant NS3 antigen-based indirect ELISA for detection of pestivirus antibodies in sheep and goats. AB - The aim of this study was to develop an indirect ELISA using the helicase domain of bovine viral diarrhoea virus (BVDV) NS3 protein instead of full-length NS3 protein for detection of BVDV and BDV antibodies in sheep and goats and its validation by comparing its sensitivity and specificity with virus neutralization test (VNT) as the reference test. The purified 50 kDa recombinant NS3 protein was used as the coating antigen in the ELISA. The optimal concentration of antigen was 320 ng/well at a serum dilution of 1:20 and the optimal positive cut-off optical density value was 0.40 based on test results of 418 VNT negative sheep and goat sera samples. When 569 serum samples from sheep (463) and goats (106) were tested, the ELISA showed a sensitivity of 91.71% and specificity of 94.59% with BVDV VNT. A good correlation (93.67%) was observed between the two tests. It showed a sensitivity of 85% and specificity of 86.6% with VNT in detecting BDV antibody positive or negative samples. This study demonstrates the efficacy of truncated recombinant NS3 antigen based ELISA for seroepidemiological study of pestivirus infection in sheep and goats. PMID- 25118570 TI - HOIL-1L functions as the PKCzeta ubiquitin ligase to promote lung tumor growth. AB - RATIONALE: Protein kinase C zeta (PKCzeta) has been reported to act as a tumor suppressor. Deletion of PKCzeta in experimental cancer models has been shown to increase tumor growth. However, the mechanisms of PKCzeta down-regulation in cancerous cells have not been previously described. OBJECTIVES: To determine the molecular mechanisms that lead to decreased PKCzeta expression and thus increased survival in cancer cells and tumor growth. METHODS: The levels of expression of heme-oxidized IRP2 ubiquitin ligase 1L (HOIL-1L), HOIL-1-interacting protein (HOIP), Shank-associated RH domain-interacting protein (SHARPIN), and PKCzeta were analyzed by Western blot and/or quantitative real-time polymerase chain reaction in different cell lines. Coimmunoprecipitation experiments were used to demonstrate the interaction between HOIL-1L and PKCzeta. Ubiquitination was measured in an in vitro ubiquitination assay and by Western blot with specific antibodies. The role of hypoxia-inducible factor (HIF) was determined by gain/loss-of-function experiments. The effect of HOIL-1L expression on cell death was investigated using RNA interference approaches in vitro and on tumor growth in mice models. Increased HOIL-1L and decreased PKCzeta expression was assessed in lung adenocarcinoma and glioblastoma multiforme and documented in several other cancer types by oncogenomic analysis. MEASUREMENTS AND MAIN RESULTS: Hypoxia is a hallmark of rapidly growing solid tumors. We found that during hypoxia, PKCzeta is ubiquitinated and degraded via the ubiquitin ligase HOIL-1L, a component of the linear ubiquitin chain assembly complex (LUBAC). In vitro ubiquitination assays indicate that HOIL-1L ubiquitinates PKCzeta at Lys-48, targeting it for proteasomal degradation. In a xenograft tumor model and lung cancer model, we found that silencing of HOIL-1L increased the abundance of PKCzeta and decreased the size of tumors, suggesting that lower levels of HOIL-1L promote survival. Indeed, mRNA transcript levels of HOIL-1L were elevated in tumor of patients with lung adenocarcinoma, and in a lung adenocarcinoma tissue microarray the levels of HOIL-1L were associated with high-grade tumors. Moreover, we found that HOIL-1L expression was regulated by HIFs. Interestingly, the actions of HOIL-1L were independent of LUBAC. CONCLUSIONS: These data provide first evidence of a mechanism of cancer cell adaptation to hypoxia where HIFs regulate HOIL-1L, which targets PKCzeta for degradation to promote tumor survival. We provided a proof of concept that silencing of HOIL-1L impairs lung tumor growth and that HOIL-1L expression predicts survival rate in cancer patients suggesting that HOIL-1L is an attractive target for cancer therapy. PMID- 25118575 TI - Feasibility of a synthetic temporal bone for training in mastoidectomy: face, content, and concurrent validity. AB - OBJECTIVE: To investigate the face, content, and concurrent validity of the synthetic Pettigrew temporal bone (PTB) for mastoidectomy training as compared with cadaveric temporal bone (CTB). STUDY DESIGN: A prospective evaluation study. METHODS: Participants were invited to perform a step-by-step modified radical mastoidectomy using both bones and complete a 22-item, 5-point Likert scale questionnaire. The questionnaire is divided into 4 domains: face validity (FV), global content (GC), task-specific content (TSC), and curriculum recommendation (CR). RESULTS: Thirty-six experts and 89 trainees completed all tasks, 63 using CTB and 62 using PTB. The PTB median FV was 4 (IQR: 4-5), GC of 4 (IQR: 4-5), TSC of 4 (IQR: 3-4), and CR of 4 (IQR: 4-5). The CTB was rated significantly higher than PTB by both groups in all domains; CTB FV: 5 (IQR: 4-5), GC: 5 (IQR: 4-5), TSC: 5 (IQR: 4-5), and CR: 5 (IQR: 5-5), p < 0.001 for each. Trainees rated PTB significantly higher than experts in all domains. There was no statistically significant difference between experts and trainees in rating the CTB in all domains. PTB gives similar haptic feedback to CTB, allows the use of suction and irrigation, has the important landmarks painted for identification, and contains articulating ossicles. The facial nerve anatomy was found to be inaccurate around the region of the second genu. CONCLUSION: Participants found PTB to be valid for teaching some, yet not all, aspects of mastoid surgery, and experts agreed that it could improve global transferrable otologic skills. It is essential that the facial nerve anatomy is addressed before recommending this model. PMID- 25118576 TI - Hearing preservation cochlear implantation in adolescents. AB - OBJECTIVE: This study describes our experience of cochlear implantation (CI) with hearing preservation in adolescents. Our aim was to determine if hearing preservation is successful in this population, if the preserved hearing is maintained, and what the potential benefit of preserving hearing in this population is. PATIENTS: Fourteen profoundly deaf adolescents with preservation of low-frequency hearing (125, 250, and 500 Hz). INTERVENTION: Twelve adolescents had a single-sided CI, and two had bilateral CI. All were having their first implantation, and all patients had hearing preservation surgery (soft surgery). MAIN OUTCOME MEASURES: Hearing preservation was measured with preoperative and postoperative pure-tone audiograms. Speech audiometry was performed before implantation and at subsequent follow-up appointments. RESULTS: Hearing preservation (measurable hearing thresholds) was achieved in 13 of 14 patients. Average follow-up was 2 years 10 months (range, 4 mo-4 yr 9 mo). Three of 13 patients with initial successful hearing preservation had deterioration of their hearing at subsequent follow-up. The addition of naturally preserved hearing to the cochlear implant improved speech audiometry scores compared with using the implants in isolation. CONCLUSION: This study demonstrates that residual hearing can be consistently preserved and maintained in adolescents during the short /medium-term using a soft surgical technique to insert standard-length electrodes. The potential benefit of preserving residual low-frequency hearing seems to be improvement in speech discrimination in challenging hearing conditions, although larger studies are required. PMID- 25118578 TI - Minimal Growth of Intracochlear Schwannoma Over 7 Years. PMID- 25118577 TI - The correlation between obesity, obstructive sleep apnea, and superior semicircular canal dehiscence: a new explanation for an increasingly common problem. AB - OBJECTIVE: To investigate rates of obesity and obstructive sleep apnea (OSA) in patients with a diagnosis of superior semicircular canal dehiscence (SSCD). STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary referral centers. PATIENTS: Thirty-one patients with SSCD were identified from patient records at Yale between January 1, 2003 and August 1, 2013 and from the University of Cincinnati between November 1, 2008 and November 1, 2013. The control cohort consisted of 100 consecutive adult patients who obtained high-resolution CT imaging of their temporal bones at Yale University for any reason. INTERVENTIONS: CT images were reviewed by two authors in double blind fashion and patient data was analyzed statistically. MAIN OUTCOME MEASURES: Rates of OSA, body mass index (BMI), and presence of tegmental defects in patients with SSCD were compared to the control cohort. RESULTS: The 31 patients with SSCD demonstrated higher BMIs [SSCD avg. 31.62, standard deviation (SD) 8.6 vs. no SSCD 28.01, SD 6.3, P = 0.036], rates of OSA (SSCD 29.03% vs. no SSCD 7.00, P = 0.001), and rates of tegmental defects (SSCD avg. 64.5% vs. no SSCD 16%, P = 1.24 * 10(-7)), in comparison to the control cohort. SSCD was found in 6 of 100 consecutively reviewed adult CT scans and in 0 of 41 scans obtained in those under 17 years of age. CONCLUSIONS: Patients with SSCD demonstrated higher BMIs, higher rates of OSA, and were more likely to have accompanying tegmental defects. These results may support a possible causality between increased intracranial pressure and the formation of superior semicircular canal dehiscence. PMID- 25118579 TI - A United Kingdom survey of concerns, needs, and priorities reported by patients diagnosed with acoustic neuroma. AB - INTRODUCTION: The Patient Concerns Inventory-Acoustic Neuroma (PCI-AN) was developed to explore specifically the concerns that patients would like to discuss during their clinic consultation. The PCI covers a range of issues including hearing, intimacy, fatigue, financial/benefits, relationships, regret, and support for family. It also lists multidisciplinary team (MDT) members that patients would like to see or be referred on to. METHOD: The PCI-AN was emailed to members of the British Acoustic Neuroma Association. RESULTS: A total of 465 complete (54.5%) responses were received. There were 284 female and 181 male subjects. Overall, the most common treatment modality was surgical excision (47%). A quarter of the study cohort had stereotactic radiosurgery, whereas 23% were conservatively managed with interval MRI scanning. The remaining 5% had both surgery and stereotactic radiosurgery. From the 55-item PCI-AN, the most commonly selected issues that patients wanted to talk about were related to the physical and functional well-being and treatment received. Tinnitus was the most frequently selected issue (46%), followed by fatigue/tiredness (43%), dizziness (33%), further investigation (39%), acoustic neuroma treatment (38%), and energy levels (32%). More than a quarter of the respondents had fears of their acoustic neuroma recurring (29%), had concerns about their facial appearance/ palsy (29%), or suffered pain in the head and neck region (26%). The 3 health-care professionals patients most wanted to talk with either in clinic or by referral were as follows: ENT/neurosurgeon (39%), vestibular (balance) physiotherapist (39%), and audiologist (39%). Although it was unknown how many respondents had facial palsy, 21% wanted to see a facial palsy physiotherapist, and another 10% sought referral to a plastic surgeon. CONCLUSION: The PCI-AN has shed light on an interesting array of issues, which may be overlooked by clinicians in busy skull base clinic. The PCI-AN allows for patient-directed consultation and ultimately empowers them to be actively involved in the management of their health. PMID- 25118580 TI - Graft take-rates after tympanoplasty: results from a prospective ear surgery database. AB - OBJECTIVE: To present a prospective ear surgery database and investigate the graft take-rate and prognostic factors for graft take-rate in tympanoplasty using the database. STUDY DESIGN: Prospective database study. SETTING: Tertiary referral center. PATIENTS: A total of 1606 cases undergoing tympanoplasty types I to IV were registered in the database in the period from February 2004 to November 2013. INTERVENTION: A total of 837 cases underwent myringoplasty/tympanoplasty type I. MAIN OUTCOME MEASURE: Graft take-rate and prognostic factors (age, discharge at time of surgery, tuba function, technique, graft material, and revision surgery) for tympanoplasty type I were studied. A comparison with the graft take-rates for tympanoplasty types II to IV and/or cholesteatoma was made. RESULTS: A user-friendly ear surgery database with fast data entry and direct import of audiometric data was developed. The graft take rate was found to be 93.0% at 2 to 6 months and 86.6% at more than 12 months. Except for a discharging ear at the time of surgery, no significant differences using chi2 test of association were found when comparing graft take-rates for different prognostic factors or more advanced tympanoplasty with or without cholesteatoma. A long-term graft take-rate overestimation of 6% was found if cases with defaulted follow-up because of early reperforation were not included. CONCLUSION: A prospective database can be used to study prognostic factors and reduce bias in reporting the graft take-rate. Prospective databases are needed for high-quality longitudinal studies but require a continuous and daily effort of involved surgeons and therefore need to be convenient and fast to use. PMID- 25118581 TI - Assessing Treatment Efficacy and Progression of Necrotizing Otitis Externa. PMID- 25118582 TI - Cochlear Implantation in the Setting of Cochlear Ossification as Sequela of Malarial Meningitis. PMID- 25118583 TI - Neurofibromatosis 2 invasion of the internal auditory canal wall: clinical significance. AB - OBJECTIVE: To describe the infiltration of severe phenotype ("Wishart") neurofibromatosis type 2 (NF2)-related vestibular nerve schwannomas (VSs) into the internal auditory canal wall in contrast to sporadic VS and the milder ("Gardner") phenotype NF2-related VS. STUDY DESIGN: Retrospective case series involving microscopic examination and review of clinical history. SETTING: Temporal bone laboratory, harboring 849 documented pairs of decalcified, formalin fixed, celloidin-embedded, sectioned human temporal bones (hTBs) with clinical history. SUBJECTS AND METHODS: Histologic sections from 56 patients who had been treated by the House Clinic for VS and who had pledged their temporal bones were identified in the data base of the laboratory. Twenty-four hTBs were from individuals with NF2.Each series of sections was examined microscopically for evidence of invasion of the walls of the internal auditory canal (IAC), hearing thresholds, speech discrimination, score (SDS), and tumor recurrence. RESULTS: Infiltration of the walls of the IAC by small buds of VS was found in 17 of the 24 NF2 hTBs. The only 2 NF2 without invasion were from an elderly patient with the milder (Gardner) form of NF2. Ten of the 12 NF2 patients had undergone surgery for the removal of their tumor, but residual tumor remained in the bone surrounding the IAC. Invasive VS were associated with poorer hearing thresholds at 250, 500, 1,000, and 2,000 Hz and lower SDS score. A relationship between invasion and recurrence was not statistically significant. CONCLUSION: The majority of IAC tumors associated with the severe "Wishart" phenotype demonstrate bone invasion within the IAC. Invasion of bone was associated with poorer hearing. The invasive nature of NF2-associated tumors may partially explain their higher recurrence rate after resection. Surgeons managing NF2-related VS should be aware of the small infiltrations of the wall of the IAC when removing these tumors to minimize recurrence. PMID- 25118584 TI - Round window electrocochleography and speech perception outcomes in adult cochlear implant subjects: comparison with audiometric and biographical information. AB - HYPOTHESIS: Intraoperative round window (RW) electrocochleography (ECoG) can help predict speech perception outcomes in adult cochlear implant (CI) recipients. BACKGROUND: Speech perception outcomes using CIs are highly variable. Recent data demonstrated that intraoperative ECoG could account for nearly half the variance in postoperative word scores. The present study seeks to update this correlation with a larger sample size and determine if addition of clinical variables improves the prediction. METHODS: Intraoperative RW ECoG was performed in adult subjects undergoing CI. Amplitudes of the ongoing response to tone bursts of multiple frequencies at 85 to 95 dB HL were summed to obtain the total response (ECoG-TR). ECoG-TR was correlated with postoperative speech perception scores. Multiple linear regression was used to combine clinical factors with the ECoG-TR. RESULTS: The ECoG-TR accounted for 40% of the variance in CNC word scores (n = 32). The preoperative pure tone average (PTA) was the only clinical factor with a significant correlation (r2 = 20%). The ability to predict word scores using ECoG TR and PTA, or after addition of age and duration of hearing loss, was not significantly different from using ECoG-TR alone. For 2 outliers, ECoG-TR predicted a better word score than obtained. CONCLUSIONS: The measurement of cochlear physiology before CI, reduced to a single variable, is a better predictor of postoperative speech perception than common clinical factors. Additional analysis of the outliers showed that waveform morphology can provide distinct information in individual cases. PMID- 25118586 TI - Why no Unilateral Vestibular Atelectasis? PMID- 25118585 TI - Inactivation of specific Pseudomonas aeruginosa biofilm factors does not alter virulence in infected cholesteatomas. AB - HYPOTHESIS: When experimental cholesteatomas are infected with Pseudomonas aeruginosa (PA) mutants lacking factors associated with the formation of biofilms, host defenses are more effective against these strains when compared with wild-type strains (PAO1 and OPPA8) in preventing tissue destruction. BACKGROUND: Previous studies have identified biofilms within chronically infected aural cholesteatomas. These infected cholesteatomas are associated with increased tissue destruction. Because biofilms are highly resistant to host defenses leading to prolonged infection, we propose that the biofilm phenotype of P. aeruginosa may be a virulence factor leading to persistence of infection and increased tissue destruction. METHODS: Aural cholesteatomas were induced in Mongolian gerbils. At the time of induction, the ear canals were inoculated with wild-type (PAO1 and OPPA8) and biofilm-deficient (PAO1 DeltapilA, PAO1 algD::aacC1 and PAO1 galU::aacC1) strains of P. aeruginosa. After 8 weeks, the size of the cholesteatomas and levels of bone destruction and deposition were measured using microCT scanning and double fluorochrome bone labeling. RESULT: Infected cholesteatomas resulted in increased growth, bone destruction, and bone deposition when compared with vehicle-only controls. We observed no differences between the wild-type (biofilm forming) and the biofilm-deficient strains of P. aeruginosa. CONCLUSION: Our hypothesis that biofilm formation is a virulence factor in cholesteatomas infected with P. aeruginosa was not supported. A number of interpretations of these data are reasonable. It is possible that biofilms are not critical in infected cholesteatomas. Alternatively, the mutants that are deficient in generating biofilms in vitro may be able to form effective biofilms in vivo using alternative pathways. PMID- 25118587 TI - "Off-on" electrochemiluminescence system for sensitive detection of ATP via target-induced structure switching. AB - An "off-on" electrochemiluminescence (ECL) strategy was constructed for highly sensitive and selective detection of adenosine 5'-triphosphate (ATP) with a quantum dots (QDs) modified electrode and a DNAzyme signal probe. The immobilized QDs were functionalized with a DNA sequence (DNA1) and then aptamer for recognition of target analyte. The signal probe was prepared by assembling another DNA sequence (DNA2) and G-quadruplex on gold nanoparticle via Au-S chemistry, which was used to bind the probe to electrode surface through a hybridization reaction with aptamer and hemin for forming G-quadruplex/hemin DNAzyme, respectively. Upon the sandwich hybridization of DNA1-aptamer-DNA2, the signal probe could be captured on the aptasensor to catalyze the reduction of dissolved oxygen, the coreactant for cathodic ECL emission of QDs, leading to a decrease of ECL intensity and thus the "off" state. In the presence of target, its recognition by aptamer led to the release of aptamer from electrode surface and decreased the amount of captured signal probe, thus the ECL emission was in its "on" state. The "off-on" strategy resulted from the target-induced structure switching could be used for specific detection of ATP with a linear range of 8 2000 nM and a detection limit of 7.6 nM. The proposed aptasensor could be successfully applied in the ECL detection of ATP in human serum. This method could resist environmental interfering agents and be extended for sensitive and reliable detection of a wide range of analytes in complex sample. PMID- 25118588 TI - Fate and transport of selected estrogen compounds in Hawaii soils: effect of soil type and macropores. AB - The fate and transport of estrogen compounds in the environment is of increasing concern due to their potential impact on freshwater organisms, ecosystems and human health. The behavior of these compounds in batch experiments suggests low mobility, while field studies indicate the persistence of estrogen compounds in the soil with the possibility of migration to surface water as well as groundwater. To better understand the movement of these chemicals through soils, we examined their transport in three different Hawaiian soils and two aqueous matrices. The three different soils used were an Oxisol, a Mollisol and a cinder, characterized by different mineralogical properties and collected at depths of 60 90 cm and 210-240 cm. Two liquid matrices were used; deionized (DI) water containing calcium chloride (CaCl2), and recycled water collected from a wastewater treatment facility. The experiments were conducted in packed and structured columns. Non-equilibrium conditions were observed during the study, especially in the structured soil. This is believed to be primarily related to the presence of macropores in the soil. The presence of macropores resulted in reduced contact time between soil and estrogens, which facilitated their transport. We found that the organic carbon content and mineralogical composition of the soils had a profound effect on the transport of the estrogens. The mobility of estrone (E1) and 17beta-estradiol (E2) was greater in cinder than in the other soils. In column experiments with recycled water, earlier breakthrough peaks and longer tails of estrogens were produced compared to those observed using DI water. The use of recycled water for agricultural purposes and the siting of septic tanks and cesspools should be critically reviewed in light of these findings, especially in areas where groundwater is the primary source of potable water, such as Hawaii. PMID- 25118590 TI - Preliminary study of an offline simultaneous determination of metoprolol tartrate and hydrochlorothiazide in powders and tablets by reflectance near-infrared spectroscopy. AB - A preliminary study of the feasibility of using near-infrared spectroscopy (NIRS) for the offline simultaneous determination of metoprolol tartrate (MTP) and hydrochlorothiazide (HTZ) in powders and tablets has been carried out. An industrial tableting process was simulated using an instrumented tablet press replicator - PressterTM. Conventional reference analytics were replaced with gravimetric analysis. The NIRS models for powder and tablet analysis were developed using 55 samples, and tested on 80 independent samples. Powder mixture components were weighed in glass vials to collect reference values, mixed and manually transferred to a tablet press replicator and compacted to form tablets. NIRS calibration models were developed using spectral and gravimetric reference data. The two model drugs were simultaneously quantified exhibiting root mean squared error of prediction (RMSEP) of 1.69 and 1.31 mg for HTZ powder and tablet samples, respectively, and RMSEP of 3.15 and 3.00 mg for MTP powder and tablet samples, respectively. NIRS analysis of MTP and HTZ in powder and tablet form has not been reported elsewhere. PMID- 25118591 TI - Effect of simulated precompression, compression pressure and tableting speed on an offline diffuse transmittance and reflectance near-infrared spectral information of model intact caffeine tablets. AB - Near-infrared spectroscopy (NIRS) is used in the pharmaceutical industry for monitoring drug content during the tablet manufacturing process. It is of critical importance to understand the effect of process factors on NIRS performance. Design of Experiments (DoE) methodology was applied in this work for the systematic study of the effects of compression pressure, precompression pressure and tableting speed on an average Euclidean distance (AED), which reflects spectral features of the tablets, and root mean-squared error of prediction (RMSEP) as key performance indicator of NIRS calibration models. Caffeine tablets were manufactured in 17 experimental runs in accordance with D optimal design. Developed diffuse transmittance (DT) and diffuse reflectance (DR) calibration models were tested on five independent test sets to confirm the conclusions of the DoE. Compression pressure and tableting speed have shown significant effect on the studied responses in DT mode, whereas all three studied factors have shown a significant effect in DR mode. Significant factors were considered in the development of the global calibration models. The authors suggest further study of RMSEP and AED responses to draw reliable conclusions on the effects of tableting process factors. The global calibration model in DT mode has shown superior performance compared to DR mode. PMID- 25118589 TI - RasGRP3 limits Toll-like receptor-triggered inflammatory response in macrophages by activating Rap1 small GTPase. AB - Host immune cells can detect and destruct invading pathogens via pattern recognition receptors. Small Rap GTPases act as conserved molecular switches coupling extracellular signals to various cellular responses, but their roles as regulators in Toll-like receptor (TLR) signalling have not been fully elucidated. Here we report that Ras guanine nucleotide-releasing protein 3 (RasGRP3), a guanine nucleotide-exchange factor activating Ras and Rap1, limits production of proinflammatory cytokines (especially IL-6) in macrophages by activating Rap1 on activation by low levels of TLR agonists. We demonstrate that RasGRP3, a dominant member of RasGRPs in macrophages, impairs TLR3/4/9-induced IL-6 production and relieves dextrane sulphate sodium-induced colitis and collagen-induced arthritis. In RasGRP3-deficient RAW264.7 cells obtained by CRISPR-Cas9 genome editing, TLR3/4/9-induced activation of Rap1 was inhibited while ERK1/2 activation was enhanced. Our study suggests that RasGRP3 limits inflammatory response by activating Rap1 on low-intensity pathogen infection, setting a threshold for preventing excessive inflammatory response. PMID- 25118593 TI - Effect of seasonal variation on adult clinical laboratory parameters in Rwanda, Zambia, and Uganda: implications for HIV biomedical prevention trials. AB - OBJECTIVES: To investigate the effect of seasonal variation on adult clinical laboratory parameters in Rwanda, Zambia, and Uganda and determine its implications for HIV prevention and other clinical trials. METHODS: Volunteers in a cross-sectional study to establish laboratory reference intervals were asked to return for a seasonal visit after the local season had changed from dry to rainy or vice versa. Volunteers had to be clinically healthy, not pregnant and negative for HIV, Hepatitis B and C, and syphilis infection at both visits. At each visit, blood was taken for measurement of hemoglobin, haematocrit, mean corpuscular volume, red blood cells, platelets, total white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, CD4/CD8 T cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct bilirubin, total bilirubin, total immunoglobulin gamma, total protein, creatinine, total amylase, creatine phosphokinase and lactate dehydrogenase (LDH). Consensus dry season reference intervals were applied to rainy season values (and vice versa) and the proportion of 'out-of-range' values determined. Percentage differences between dry and rainy season parameter mean values were estimated. RESULTS: In this cohort of 903 volunteers, less than 10.0% of consensus parameter (except LDH) values in one season were "out-of-range" in the other. Twenty-two (22) percent of rainy season LDH values fell outside of the consensus dry season interval with the higher values observed in the rainy season. Variability between consensus seasonal means ranged from 0.0% (total WBC, neutrophils, monocytes, basophils, and direct bilirubin) to 40.0% (eosinophils). Within sites, the largest seasonal variations were observed for monocytes (Masaka, 11.5%), LDH (Lusaka, 21.7%), and basophils (Kigali, 22.2%). CONCLUSIONS: Seasonality had minimal impact on adult clinical laboratory parameter values in Rwanda, Zambia, and Uganda. Seasonal variation may not be an important factor in the evaluation of adult clinical laboratory parameters in HIV prevention and other clinical trials in these countries. PMID- 25118592 TI - Discovery of a rare pterosaur bone bed in a cretaceous desert with insights on ontogeny and behavior of flying reptiles. AB - A pterosaur bone bed with at least 47 individuals (wing spans: 0.65-2.35 m) of a new species is reported from southern Brazil from an interdunal lake deposit of a Cretaceous desert, shedding new light on several biological aspects of those flying reptiles. The material represents a new pterosaur, Caiuajara dobruskii gen. et sp. nov., that is the southermost occurrence of the edentulous clade Tapejaridae (Tapejarinae, Pterodactyloidea) recovered so far. Caiuajara dobruskii differs from all other members of this clade in several cranial features, including the presence of a ventral sagittal bony expansion projected inside the nasoantorbital fenestra, which is formed by the premaxillae; and features of the lower jaw, like a marked rounded depression in the occlusal concavity of the dentary. Ontogenetic variation of Caiuajara dobruskii is mainly reflected in the size and inclination of the premaxillary crest, changing from small and inclined (~ 115 degrees ) in juveniles to large and steep (~ 90 degrees ) in adults. No particular ontogenetic features are observed in postcranial elements. The available information suggests that this species was gregarious, living in colonies, and most likely precocial, being able to fly at a very young age, which might have been a general trend for at least derived pterosaurs. PMID- 25118594 TI - Increased lymph node yield in colorectal cancer is not necessarily associated with a greater number of lymph node positive cancers. AB - The presence of lymph node metastasis is a key prognostic factor in colorectal cancer and lymph node yield is an important parameter in assessing the quality of histopathology reporting of colorectal cancer excision specimens. This study assesses the trend in lymph node evaluation over time in a single institution and the relationship with the identification of lymph node positive tumours. It compares the lymph node yield of a contemporary dataset compiled from the histopathology reports of 2178 patients who underwent surgery for primary colorectal cancer between 2005 and 2012 with that of a historic dataset compiled from the histopathology reports of 1038 patients who underwent surgery for colorectal cancer at 5 yearly intervals from 1975 to 2000. The mean lymph node yield was 14.91 in 2005 rising to 21.38 in 2012. In 2012 92.9% of all cases had at least 12 lymph nodes examined. Comparison of the mean lymph node yield and proportion of Dukes C cases shows a significant increase (Pearson correlation = 0.927, p = 0.001) in lymph node yield while there is no corresponding significant trend in the proportion of Dukes C cases (Pearson correlation = -0.138, p = 0.745). This study shows that there is increasing yield of lymph nodes from colorectal cancer excision specimens. However, this is not necessarily associated with an increase number of lymph node positive cancers. Further risk stratifying of colorectal cancer requires consideration of other pathological parameters especially the presence of extramural venous invasion and relevant biomarkers. PMID- 25118595 TI - Saccharomyces boulardii modifies Salmonella typhimurium traffic and host immune responses along the intestinal tract. AB - Salmonella enterica serovar Typhimurium (ST) is an enteropathogenic Gram-negative bacterium that causes infection following oral ingestion. ST spreads rapidly along the gastrointestinal tract (GIT) and invades the intestinal epithelium to ultimately reach internal body organs. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is prescribed for prophylaxis of diarrheal infectious diseases. We previously showed that S.b-B prevents weight loss in ST-infected mice and significantly decreases bacterial translocation to the spleen and liver. This study was designed to investigate the effect of S.b-B on ST migration along the GIT and the impact of the yeast on the host's early innate immune responses. Bioluminescent imaging (BLI) was used to evaluate the effect of S.b-B on the progression of luminescent Salmonella Typhimurium (ST-lux) in the GIT of mice pretreated with streptomycin. Photonic emission (PE) was measured in GIT extracts (stomach, small intestine, cecum and colon) at various time periods post infection (PI). PE analysis revealed that, 45 min PI, ST-lux had migrated slightly faster in the mice treated with S.b-B than in the untreated infected animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice. Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably accounts for (1) the faster elimination of ST-lux in the feces, and (2) reduced translocation of ST to the spleen and liver. In the early phase of infection, S.b B also modifies the host's immune responses by (1) increasing IFN-gamma gene expression and decreasing IL-10 gene expression in the small intestine, and (2) elevating both IFN-gamma, and IL-10 mRNA levels in the cecum. BLI revealed that S.b-B modifies ST migration and the host immune response along the GIT. Study findings shed new light on the protective mechanisms of S.b-B during the early phase of Salmonella pathogenesis. PMID- 25118596 TI - Copy number variation in Thai population. AB - Copy number variation (CNV) is a major genetic polymorphism contributing to genetic diversity and human evolution. Clinical application of CNVs for diagnostic purposes largely depends on sufficient population CNV data for accurate interpretation. CNVs from general population in currently available databases help classify CNVs of uncertain clinical significance, and benign CNVs. Earlier studies of CNV distribution in several populations worldwide showed that a significant fraction of CNVs are population specific. In this study, we characterized and analyzed CNVs in 3,017 unrelated Thai individuals genotyped with the Illumina Human610, Illumina HumanOmniexpress, or Illumina HapMap550v3 platform. We employed hidden Markov model and circular binary segmentation methods to identify CNVs, extracted 23,458 CNVs consistently identified by both algorithms, and cataloged these high confident CNVs into our publicly available Thai CNV database. Analysis of CNVs in the Thai population identified a median of eight autosomal CNVs per individual. Most CNVs (96.73%) did not overlap with any known chromosomal imbalance syndromes documented in the DECIPHER database. When compared with CNVs in the 11 HapMap3 populations, CNVs found in the Thai population shared several characteristics with CNVs characterized in HapMap3. Common CNVs in Thais had similar frequencies to those in the HapMap3 populations, and all high frequency CNVs (>20%) found in Thai individuals could also be identified in HapMap3. The majorities of CNVs discovered in the Thai population, however, were of low frequency, or uniquely identified in Thais. When performing hierarchical clustering using CNV frequencies, the CNV data were clustered into Africans, Europeans, and Asians, in line with the clustering performed with single nucleotide polymorphism (SNP) data. As CNV data are specific to origin of population, our population-specific reference database will serve as a valuable addition to the existing resources for the investigation of clinical significance of CNVs in Thais and related ethnicities. PMID- 25118597 TI - Sclerostin blood levels before and after kidney transplantation. AB - BACKGROUND/AIMS: Sclerostin is secreted by osteocytes. As a circulating inhibitor of the Wnt-signaling pathway it inhibits bone formation and contributes to the development of osteoporosis. Sclerostin levels are elevated in patients with chronic kidney disease and end-stage renal disease. Since data for patients after kidney transplantation are scarce, we have prospectively measured sclerostin levels before and during the first year after renal transplantation and have examined the association of sclerostin with parameters of bone mineral metabolism and with bone mineral density. METHODS: Sclerostin levels were measured by ELISA in 42 consecutive renal transplant recipients before and at defined intervals in the first year after transplantation. Bone mineral density was measured by dual energy X-ray absorptiometry. RESULTS: Pre-transplant serum sclerostin levels were elevated in all patients (61.8 +/- 32.3 pmol/l, normal range 20-30 pmol/l). Within 15 days after transplantation and correlating with the improvement of renal function, sclerostin levels dropped to 21.0 +/- 14.7 pmol/l and subsequently increased to 23.8 +/- 14.9 and 28.0 +/- 16.8 pmol/l after 6 and 12 months, respectively (P<0.001). A linear mixed model indicated that pre transplant sclerostin levels (P<0.001) and time after transplantation (P<0.001) were the most important predictors for the rise of post-transplant sclerostin levels. No correlation was found between post-transplant sclerostin levels and bone mineral density. CONCLUSIONS: The rapid reduction of elevated serum sclerostin levels shortly after kidney transplantation parallels the improvement of renal function, but contrasts with the more delayed improvement of hyperparathyroidism. The normalization of both hormones could contribute to improved bone health after renal transplantation. PMID- 25118598 TI - Cyclic variations in incubation conditions induce adaptive responses to later heat exposure in chickens: a review. AB - Selection programs have enabled broiler chickens to gain muscle mass without similar enlargement of the cardiovascular and respiratory systems that are essential for thermoregulatory efficiency. Meat-type chickens cope with high ambient temperature by reducing feed intake and growth during chronic and moderate heat exposure. In case of acute heat exposure, a dramatic increase in morbidity and mortality can occur. In order to alleviate heat stress in the long term, research has recently focused on early thermal manipulation. Aimed at stimulation of long-term thermotolerance, the thermal manipulation of embryos is a method based on fine tuning of incubation conditions, taking into account the level and duration of increases in temperature and relative humidity during a critical period of embryogenesis. The consequences of thermal manipulation on the performance and meat quality of broiler chickens have been explored to ensure the potential application of this strategy. The physiological basis of the method is the induction of epigenetic and metabolic mechanisms that control body temperature in the long term. Early thermal manipulation can enhance poultry resistance to environmental changes without much effect on growth performance. This review presents the main strategies of early heat exposure and the physiological concepts on which these methods were based. The cellular mechanisms potentially underlying the adaptive response are discussed as well as the potential interest of thermal manipulation of embryos for poultry production. PMID- 25118599 TI - 1alpha,25-dihydroxyvitamin D3 ameliorates seawater aspiration-induced acute lung injury via NF-kappaB and RhoA/Rho kinase pathways. AB - INTRODUCTION: Inflammation and pulmonary edema are involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have reported that 1alpha,25-Dihydroxyvitamin D3 (calcitriol) suppresses inflammation, it has not been confirmed to be effective in seawater aspiration induced ALI. Thus, we investigated the effect of calcitriol on seawater aspiration-induced ALI and explored the probable mechanism. METHODS: Male SD rats receiving different doses of calcitriol or not, underwent seawater instillation. Then lung samples were collected at 4 h for analysis. In addition, A549 cells and rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with calcitriol or not and then stimulated with 25% seawater for 40 min. After these treatments, cells samples were collected for analysis. RESULTS: Results from real time PCR showed that seawater stimulation up-regulated the expression of vitamin D receptor in lung tissues, A549 cells and RPMVECs. Seawater stimulation also activates NF-kappaB and RhoA/Rho kinase pathways. However, we found that pretreatment with calcitriol significantly inhibited the activation of NF-kappaB and RhoA/Rho kinase pathways. Meanwhile, treatment of calcitriol also improved lung histopathologic changes, reduced inflammation, lung edema and vascular leakage. CONCLUSIONS: These results demonstrated that NF-kappaB and RhoA/Rho kinase pathways are critical in the development of lung inflammation and pulmonary edema and that treatment with calcitriol could ameliorate seawater aspiration-induced ALI, which was probably through the inhibition of NF-kappaB and RhoA/Rho kinase pathways. PMID- 25118603 TI - Hepatocellular carcinoma: gender differences. PMID- 25118604 TI - Microenvironment: HSF1, the troublemaker next door. PMID- 25118605 TI - Evidence for prehistoric origins of Egyptian mummification in late Neolithic burials. AB - Traditional theories on ancient Egyptian mummification postulate that in the prehistoric period (i.e. the Neolithic and Chalcolithic periods, 5th and 4th millennia B.C.) bodies were naturally desiccated through the action of the hot, dry desert sand. Although molding of the body with resin-impregnated linen is believed to be an early Pharaonic forerunner to more complex processes, scientific evidence for the early use of resins in artificial mummification has until now been limited to isolated occurrences during the late Old Kingdom (c. 2200 B.C.), their use becoming more apparent during the Middle Kingdom (c. 2000 1600 BC). We examined linen wrappings from bodies in securely provenanced tombs (pit graves) in the earliest recorded ancient Egyptian cemeteries at Mostagedda in the Badari region (Upper Egypt). Our investigations of these prehistoric funerary wrappings using a combination of gas chromatography-mass spectrometry (GC-MS) and thermal desorption/pyrolysis (TD/Py)-GC-MS have identified a pine resin, an aromatic plant extract, a plant gum/sugar, a natural petroleum source, and a plant oil/animal fat in directly AMS-dated funerary wrappings. Predating the earliest scientific evidence by more than a millennium, these embalming agents constitute complex, processed recipes of the same natural products, in similar proportions, as those utilized at the zenith of Pharaonic mummification some 3,000 years later. The antibacterial properties of some of these ingredients and the localized soft-tissue preservation that they would have afforded lead us to conclude that these represent the very beginnings of experimentation that would evolve into the famous mummification practice of the Pharaonic period. PMID- 25118607 TI - Experimental study of the vortex-induced vibration of drilling risers under the shear flow with the same shear parameter at the different Reynolds numbers. AB - A considerable number of studies for VIV under the uniform flow have been performed. However, research on VIV under shear flow is scarce. An experiment for VIV under the shear flow with the same shear parameter at the two different Reynolds numbers was conducted in a deep-water offshore basin. Various measurements were obtained by the fiber bragg grating strain sensors. Experimental data were analyzed by modal analysis method. Results show several valuable features. First, the corresponding maximum order mode of the natural frequency for shedding frequency is the maximum dominant vibration mode and multi modal phenomenon is appeared in VIV under the shear flow, and multi-modal phenomenon is more apparent at the same shear parameter with an increasing Reynolds number under the shear flow effect. Secondly, the riser vibrates at the natural frequency and the dominant vibration frequency increases for the effect of the real-time tension amplitude under the shear flow and the IL vibration frequency is the similar with the CF vibration frequency at the Reynolds number of 1105 in our experimental condition and the IL dominant frequency is twice the CF dominant frequency with an increasing Reynolds number. In addition, the displacement trajectories at the different locations of the riser appear the same shape and the shape is changed at the same shear parameter with an increasing Reynolds number under the shear flow. The diagonal displacement trajectories are observed at the low Reynolds number and the crescent-shaped displacement trajectories appear with an increasing Reynolds number under shear flow in the experiment. PMID- 25118602 TI - Mechanisms of disseminated cancer cell dormancy: an awakening field. AB - Metastases arise from residual disseminated tumour cells (DTCs). This can happen years after primary tumour treatment because residual tumour cells can enter dormancy and evade therapies. As the biology of minimal residual disease seems to diverge from that of proliferative lesions, understanding the underpinnings of this new cancer biology is key to prevent metastasis. Analysis of approximately 7 years of literature reveals a growing focus on tumour and normal stem cell quiescence, extracellular and stromal microenvironments, autophagy and epigenetics as mechanisms that dictate tumour cell dormancy. In this Review, we attempt to integrate this information and highlight both the weaknesses and the strengths in the field to provide a framework to understand and target this crucial step in cancer progression. PMID- 25118606 TI - Acute effects of particulate matter and black carbon from seasonal fires on peak expiratory flow of schoolchildren in the Brazilian Amazon. AB - BACKGROUND: Panel studies have shown adverse effects of air pollution from biomass burning on children's health. This study estimated the effect of current levels of outdoor air pollution in the Amazonian dry season on peak expiratory flow (PEF). METHODS: A panel study with 234 schoolchildren from 6 to 15 years old living in the municipality of Tangara da Serra, Brazil was conducted. PEF was measured daily in the dry season in 2008. Mixed-effects models and unified modelling repeated for every child were applied. Time trends, temperature, humidity, and subject characteristics were regarded. Inhalable particulate matter (PM10), fine particulate matter (PM2.5), and black carbon (BC) effects were evaluated based on 24-hour exposure lagged by 1 to 5 days and the averages of 2 or 3 days. Polynomial distributed lag models (PDLM) were also applied. RESULTS: The analyses revealed reductions in PEF for PM10 and PM2.5 increases of 10 ug/m(3) and 1 ug/m(3) for BC. For PM10, the reductions varied from 0.15 (confidence interval (CI)95%: -0.29; -0.01) to 0.25 l/min (CI95%: -0.40; -0.10). For PM2.5, they ranged from 0.46 (CI95%: -0.86 to -0.06) to 0.54 l/min (CI95%: 0.95; -0.14). As for BC, the reduction was approximately 1.40 l/min. In relation to PDLM, adverse effects were noticed in models based on the exposure on the current day through the previous 3 days (PDLM 0-3) and on the current day through the previous 5 days (PDLM 0-5), specially for PM10. For all children, for PDLM 0 5 the global effect was important for PM10, with PEF reduction of 0.31 l/min (CI95%: -0.56; -0.05). Also, reductions in lags 3 and 4 were observed. These associations were stronger for children between 6 and 8 years old. CONCLUSION: Reductions in PEF were associated with air pollution, mainly for lagged exposures of 3 to 5 days and for younger children. PMID- 25118608 TI - Roles of birds and bats in early tropical-forest restoration. AB - Restoration of tropical forest depended in large part on seed dispersal by fruit eating animals that transported seeds into planted forest patches. We tested effectiveness of dispersal agents as revealed by established recruits of tree and shrub species that bore seeds dispersed by birds, bats, or both. We documented restoration of dispersal processes over the first 76 months of experimental restoration in southern Mexico. Mixed-model repeated-measures randomized-block ANOVAs of seedlings recruited into experimental controls and mixed-species plantings from late-secondary and mature forest indicated that bats and birds played different roles in the first years of a restoration process. Bats dispersed pioneer tree and shrub species to slowly regenerating grassy areas, while birds mediated recruitment of later-successional species into planted stands of trees and to a lesser extent into controls. Of species of pioneer trees and shrubs established in plots, seven were primarily dispersed by birds, three by bats and four by both birds and bats. Of later-successional species recruited past the seedling stage, 13 were of species primarily dispersed by birds, and six were of species dispersed by both birds and bats. No later-successional species primarily dispersed by bats established in control or planted plots. Establishment of recruited seedlings was ten-fold higher under cover of planted trees than in grassy controls. Even pre-reproductive trees drew fruit-eating birds and the seeds that they carried from nearby forest, and provided conditions for establishment of shade-tolerant tree species. Overall, after 76 months of cattle exclusion, 94% of the recruited shrubs and trees in experimental plots were of species that we did not plant. PMID- 25118609 TI - Role of genetics in pediatric inflammatory bowel disease. AB - Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative colitis (UC), and unclassified IBD, is characterized by chronic intestinal inflammation and has a multifactorial etiology with complex interactions between genetic and environmental factors. The genetics of IBD are believed to be common and complex with over 163 associated genetic loci. However, the genetic contribution of the majority of these common loci is small, and the effect sizes are low. Although childhood onset IBD represents only 10% to 25% of all IBD cases, in depth research into the genetic networks of pediatric IBD has revealed exciting new developments and unsuspected pathways. Recent pediatric studies have revealed an increasing spectrum of human monogenic diseases with high effect sizes or penetrance that can present with IBD or IBD-like intestinal inflammation. A substantial proportion of patients with these genetic defects present with very early onset of intestinal inflammation, with onset of IBD at less than 10 years of age. There is also considerable overlap with primary immunodeficiencies and very early onset IBD. This review summarizes the current understanding of the genetics of pediatric IBD with a focus on the very early onset population and discusses the promising results from the effort of finding missing heritability of IBD from studying pediatric population. PMID- 25118610 TI - Magnesium retards the progress of the arterial calcifications in hemodialysis patients: a pilot study. AB - BACKGROUND: The aim of the study was to evaluate the impact of magnesium (Mg) on the evolution of arterial calcifications in hemodialysis patients. PATIENTS AND METHODS: Seventy-two stable hemodialysis patients were randomly allocated to two groups: 36 administered a regimen containing magnesium carbonate plus calcium acetate as a phosphate binder (Mg group), while the rest 36 received calcium acetate alone (Ca group). The presence and the progression of arterial calcifications were evaluated in plain X-rays using a simple vascular calcification score. The duration of the follow-up period was 12 months. RESULTS: Thirty-two patients of the Mg group and 27 of the Ca group completed the study. The mean time average values of the biochemical laboratories did not differ between the two groups, except serum Mg: 2.83 + 0.38 in the Mg group versus 2.52 + 0.27 mg/dl in the Ca group, p = 0.001. In 9/32 (28.12 %) patients of the Mg group and in 12/27 (44.44 %) patients of the Ca group, the arterial calcifications were worsened, p = 0.276. Moreover, in 4/32 (15.6 %) patients of the Mg group and in 0/27 (0 %) patients of the Ca group, they were improved, p = 0.040. The multivariate logistic regression analysis revealed that serum magnesium was an independent predictor for no progression of the arterial calcifications, p = 0.047. CONCLUSIONS: Magnesium probably retards the arterial calcifications in hemodialysis patients. Further clinical studies are needed to clarify whether magnesium provides cardiovascular protection to this group of patients. PMID- 25118611 TI - Beneficial dose conversion after switching from higher doses of shorter-acting erythropoiesis-stimulating agents to C.E.R.A in CKD patients in clinical practice: MINERVA Study. AB - PURPOSE: To assess whether the correction dose recommended by the summary of product characteristics was adequate and to confirm the adequacy of the recommended conversion dosing strategies from shorter-acting erythropoiesis stimulating agents (ESAs) to continuous erythropoietin receptor activator (C.E.R.A) in anaemic chronic kidney disease (CKD) patients in the clinical setting. METHODS: This was a 12-month, multicenter, prospective, observational study in anaemic CKD patients on haemodialysis and not on dialysis receiving C.E.R.A (at least one dose). RESULTS: A total of 227 patients were included (not on dialysis; n = 142; haemodialysis: n = 85). The present analysis was conducted on ESA-naive patients (not on dialysis: n = 31) and patients switched from other ESA (not on dialysis: n = 63; haemodialysis: n = 57). Both on and not on dialysis patients switched from other ESA received lower starting C.E.R.A doses than those recommended, and remained stable during the 12-month period. The higher the previous ESA dose was, the more beneficial the C.E.R.A dose conversion factor was. The proportion of patients with stable haemoglobin within the target range (11-13 g/dL) did not vary during the 12-month period both in nondialysis CKD patients and in those undergoing dialysis [baseline: 42 (66.7 %) and 34 (59.6 %); month 6: 21 (55.3 %) and 26 (50.0 %); month 12: 20 (64.5 %) and 25 (69.4 %), respectively]. In naive patients, the mean weight-adjusted C.E.R.A dose during the study (1.19 +/- 0.49 ug/kg/month) was similar to the recommended one. C.E.R.A was well tolerated. CONCLUSIONS: Conversion from shorter-acting ESAs to C.E.R.A doses lower than those recommended can efficiently maintain target haemoglobin levels both in nondialysis and haemodialysis CKD patients, particularly when switching from higher ESA doses. A monthly C.E.R.A dose of 1.2 ug/Kg seems adequate for anaemia correction. PMID- 25118613 TI - Septic complications and hospital admissions after transrectal ultrasound-guided prostate biopsy: incidence rates and outcomes in 913 consecutive biopsies. PMID- 25118612 TI - Protective effects of adiponectin on uncoupling of glomerular VEGF-NO axis in early streptozotocin-induced type 2 diabetic rats. AB - PURPOSE: To determine whether adiponectin could reduce microalbuminuria and provide renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular vascular endothelial growth factor (VEGF)-nitric oxide (NO) axis in streptozotocin-induced type 2 diabetic rats. METHODS: Wistar rats were randomly divided into normal control group, diabetic nephropathy (DN) group induced by high-fat feeding and streptozotocin, diabetic rats injected with adenovirus-expressed adiponectin (AD-AdipoQ), and diabetic rats injected with AD IRES-EGFP as control. Blood and urine samples were collected. Endothelium dependent vasodilatation (EDV) of the aorta was measured. Renal tissues were collected for CD34 immunohistochemistry. Glomerular NO and VEGF levels were measured by the Griess reaction and Western blot testing, respectively. RESULTS: Injections of AD-AdipoQ significantly increased serum adiponectin levels and reduced the urinary albumin-to-creatinine ratio in diabetic rats (P < 0.05). The levels of plasma glucose, serum insulin, high-sensitivity C-reactive protein, and malondialdehyde were significantly reduced in diabetic rats after injections of AD-AdipoQ (P < 0.05). Severe EDV impairment was observed in the DN group, which was improved by AD-AdipoQ. CD34 expression in the glomeruli was also higher in diabetic rats, indicating increased proliferation of glomerular endothelial cells. However, AD-AdipoQ improved the increased proliferation of endothelial cells in the glomeruli. Diabetic rats showed increased glomerular VEGF levels and reduced NO levels. This uncoupling of the VEGF-NO axis was partially improved by AD-AdipoQ. CONCLUSION: Adiponectin reduces the degree of microalbuminuria and has renal protective effects by improving endothelial dysfunction and uncoupling of the glomerular VEGF-NO axis in early diabetic nephropathy. PMID- 25118601 TI - A comprehensive reference transcriptome resource for the common house spider Parasteatoda tepidariorum. AB - Parasteatoda tepidariorum is an increasingly popular model for the study of spider development and the evolution of development more broadly. However, fully understanding the regulation and evolution of P. tepidariorum development in comparison to other animals requires a genomic perspective. Although research on P. tepidariorum has provided major new insights, gene analysis to date has been limited to candidate gene approaches. Furthermore, the few available EST collections are based on embryonic transcripts, which have not been systematically annotated and are unlikely to contain transcripts specific to post embryonic stages of development. We therefore generated cDNA from pooled embryos representing all described embryonic stages, as well as post-embryonic stages including nymphs, larvae and adults, and using Illumina HiSeq technology obtained a total of 625,076,514 100-bp paired end reads. We combined these data with 24,360 ESTs available in GenBank, and 1,040,006 reads newly generated from 454 pyrosequencing of a mixed-stage embryo cDNA library. The combined sequence data were assembled using a custom de novo assembly strategy designed to optimize assembly product length, number of predicted transcripts, and proportion of raw reads incorporated into the assembly. The de novo assembly generated 446,427 contigs with an N50 of 1,875 bp. These sequences obtained 62,799 unique BLAST hits against the NCBI non-redundant protein data base, including putative orthologs to 8,917 Drosophila melanogaster genes based on best reciprocal BLAST hit identity compared with the D. melanogaster proteome. Finally, we explored the utility of the transcriptome for RNA-Seq studies, and showed that this resource can be used as a mapping scaffold to detect differential gene expression in different cDNA libraries. This resource will therefore provide a platform for future genomic, gene expression and functional approaches using P. tepidariorum. PMID- 25118615 TI - Current developments in pharmacogenomics of multiple sclerosis. AB - Pharmacogenomics has a significant potential to impact how we treat diseases. It involves targeting genetically identifiable populations with therapeutic interventions that promises to yield immediate positive health outcomes with lower or no side effects. The 'trial and error' method of treatment will no longer be necessary with the successful implementation of personalized medicine. The following is an overview of some new developments in pharmacogenomics of multiple sclerosis, and how it has the potential to improve future treatment. PMID- 25118614 TI - Expression of macrophage migration inhibitory factor in the mouse neocortex and posterior piriform cortices during postnatal development. AB - Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein, participating in a vast array of cellular and biological processes. Abnormal expression of MIF has been implicated in many neurological diseases, including Parkinson's disease, epilepsy, Alzheimer's Disease, stroke, and neuropathic pain. However, the expression patterns of mif transcript and MIF protein from the early postnatal period through adulthood in the mouse brain are still poorly understood. We therefore investigated the temporal and spatial expression of MIF in the mouse neocortex during postnatal development in detail and partially in posterior piriform cortices (pPC). As determined by quantitative real-time PCR (qPCR), mif transcript gradually increased during development, with the highest level noted at postnatal day 30 (P30) followed by a sharp decline at P75. In contrast, Western blotting results showed that MIF increased constantly from P7 to P75. The highest level of MIF was at P75, while the lowest level of MIF was at P7. Immunofluorescence histochemistry revealed that MIF-immunoreactive (ir) cells were within the entire depth of the developed neocortex, and MIF was heterogeneously distributed among cortical cells, especially at P7, P14, P30, and P75; MIF was abundant in the pyramidal layer within pPC. Double immunostaining showed that all the mature neurons were MIF-ir and all the intensely stained MIF ir cells were parvalbumin positive (Pv +) at adult. Moreover, it was demonstrated that MIF protein localized in the perikaryon, processes, presynaptic structures, and the nucleus in neurons. Taken together, the developmentally regulated expression and the subcellular localization of MIF should form a platform for an analysis of MIF neurodevelopmental biology and MIF-related nerve diseases. PMID- 25118616 TI - Hip dislocations after 2,734 elective unilateral fast-track total hip arthroplasties: incidence, circumstances and predisposing factors. AB - STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To investigate the incidence of hip dislocation 90 days after total hip arthroplasty in relation to time after surgery, mechanism of dislocation and predisposing factors. METHODS: Prospective data on preoperative patient characteristics from six Danish arthroplasty departments with similar fast-track approaches were cross referenced with the Danish National Patient Registry for complete 90-day follow up on readmissions, including emergency-room contacts. Complete patient files and postoperative radiographs were reviewed in case of dislocations. Unadjusted comparisons were made using t test/Chi-square analyses, while evaluation of risk factors potentially predisposing to dislocations was done using uni- and multivariate regression analysis. RESULTS: A total of 2,734 consecutive unselected procedures were available for analysis, of which 65 (2.4 %) had dislocations. Of these, eight were during index admission and five were treated and discharged from the emergency room. Mechanisms of dislocation were most often movement while supine or sitting for the first 30 days and due to squatting/bending from day 31 to 90. The 65 patients with dislocations had suboptimal cup placement in 34 (52.3 %), and a femoral head size of <36 mm in 20 (30.8 %) cases. Predisposing factors of dislocation were age >=75 [OR:1.96 (1.18 3.38)], pharmacologically treated psychiatric disease [OR:2.37 (1.29-4.36)] and department of surgery [OR:2.27 (1.31-3.40)] but not hospital stay of <4 days. Departments with recommendations for activity restrictions had fewer dislocations than a department without restrictions. CONCLUSIONS: Patients >=75 years and with pharmacologically treated psychiatric disease may be at increased risk of dislocations after fast-track total hip arthroplasty. Further studies including detailed information on patient and prosthesis characteristics, and activity restrictions are needed to reduce the risk of dislocation. PMID- 25118617 TI - An allosteric model of the inositol trisphosphate receptor with nonequilibrium binding. AB - The inositol trisphosphate receptor (IPR) is a crucial ion channel that regulates the Ca(2+) influx from the endoplasmic reticulum (ER) to the cytoplasm. A thorough study of the IPR channel contributes to a better understanding of calcium oscillations and waves. It has long been observed that the IPR channel is a typical biological system which performs adaptation. However, recent advances on the physical essence of adaptation show that adaptation systems with a negative feedback mechanism, such as the IPR channel, must break detailed balance and always operate out of equilibrium with energy dissipation. Almost all previous IPR models are equilibrium models assuming detailed balance and thus violate the dissipative nature of adaptation. In this article, we constructed a nonequilibrium allosteric model of single IPR channels based on the patch-clamp experimental data obtained from the IPR in the outer membranes of isolated nuclei of the Xenopus oocyte. It turns out that our model reproduces the patch-clamp experimental data reasonably well and produces both the correct steady-state and dynamic properties of the channel. Particularly, our model successfully describes the complicated bimodal [Ca(2+)] dependence of the mean open duration at high [IP3], a steady-state behavior which fails to be correctly described in previous IPR models. Finally, we used the patch-clamp experimental data to validate that the IPR channel indeed breaks detailed balance and thus is a nonequilibrium system which consumes energy. PMID- 25118619 TI - Laser desorption with corona discharge ion mobility spectrometry for direct surface detection of explosives. AB - We present a new highly sensitive technique for the detection of explosives directly from the surface using laser desorption-corona discharge-ion mobility spectrometry (LD-CD-IMS). We have developed LD based on laser diode modules (LDM) and the technique was tested using three different LDM (445, 532 and 665 nm). The explosives were detected directly from the surface without any further preparation. We discuss the mechanism of the LD and the limitations of this technique such as desorption time, transport time and desorption area. After the evaluation of experimental data, we estimated the potential limits of detection of this method to be 0.6 pg for TNT, 2.8 pg for RDX and 8.4 pg for PETN. PMID- 25118618 TI - The effectiveness of interventions for ageing workers on (early) retirement, work ability and productivity: a systematic review. AB - PURPOSE: To systematically summarise the literature on the effects of interventions for ageing workers that address work-related measures of sustainable employability, i.e. (early) retirement, work ability and work productivity. METHODS: A systematic review was performed by searching five electronic databases for relevant studies published between January 1992 and February 2014. Randomised controlled trials (RCTs) and quasi-experimental intervention studies were included. The study population included workers aged >=40 years, and the measured outcomes were positive indicators of labour force participation, i.e. (early) retirement, work ability and work productivity. The methodological quality of each included study was assessed, and best-evidence synthesis was applied to draw conclusions about the evidence for the effectiveness of each outcome. RESULTS: Four studies met the inclusion criteria. The interventions were diverse and ranged from individual (e.g. exercise) programmes to workplace programmes. Limited evidence for a favourable effect on early retirement was found. Insufficient evidence was found for the remaining outcomes, i.e. work ability and productivity, due to a lack of high-quality studies and consistent findings. CONCLUSIONS: Insufficient and limited evidence is available for a favourable effect of interventions to promote work-related components of sustainable employability in ageing workers. This is due to a scarcity of RCTs and inconsistent findings between the limited number of studies. Additional intervention studies are needed to support evidence-based decision making to prolong a healthy and productive working life for ageing workers. PMID- 25118621 TI - Targeting the vasculature for cerebroprotection in the immature brain. PMID- 25118622 TI - Joep MA Lange. PMID- 25118620 TI - Noninvasive detection of sleep/wake changes and cataplexy-like behaviors in orexin/ataxin-3 transgenic narcoleptic mice across the disease onset. AB - Sleep and behavioral monitoring of young mice is necessary for understating the progress of symptoms in congenital and acquired diseases associated with sleep and movement disorders. In the current study, we have developed a non-invasive sleep monitoring system that identifies wake and sleep patterns of newborn mice using a simple piezoelectric transducer (PZT). Using this system, we have succeeded in detecting age-dependent occurrences and changes in sleep fragmentation of orexin/ataxin-3 narcoleptic mice (a narcoleptic mouse model with postnatal hypocretin/orexin cell death) across the disease onset. We also detected REM sleep/cataplexy patterns (i.e., immobility with clear heartbeat [IMHB] signals due to the flaccid posture) by the PZT system, and found that sudden onset of REM sleep-like episodes specifically occur in narcoleptic, but not in wild type mice, suggesting that these episodes are likely cataplexy. In contrast, gradual onset of IMHB likely reflects occurrence of REM sleep. In summary, we have shown that the PZT system is useful as a non-invasive sleep and behavior monitoring system to analyze the developmental aspects of sleep and movement disorders in mice models. PMID- 25118624 TI - Crossover from Josephson effect to single interface Andreev reflection in asymmetric superconductor/nanowire junctions. AB - We report on the fabrication and characterization of symmetric nanowire-based Josephson junctions, that is, Al- and Nb-based junctions, and asymmetric junctions employing superconducting Al and Nb. In the symmetric junctions, a clear and pronounced Josephson supercurrent is observed. These samples also show clear signatures of subharmonic gap structures. At zero magnetic field, a Josephson coupling is found for the asymmetric Al/InAs-nanowire/Nb junctions as well. By applying a magnetic field above the critical field of Al or by raising the temperature above the critical temperature of Al the junction can be switched to an effective single-interface superconductor/nanowire structure. In this regime, a pronounced zero-bias conductance peak due to reflectionless tunneling has been observed. PMID- 25118623 TI - RAS mutations in benign epithelial tumors associated with BRAF inhibitor treatment of melanoma. PMID- 25118625 TI - Bioinformatics analysis of biomarkers and transcriptional factor motifs in Down syndrome. AB - In this study, biomarkers and transcriptional factor motifs were identified in order to investigate the etiology and phenotypic severity of Down syndrome. GSE 1281, GSE 1611, and GSE 5390 were downloaded from the gene expression ominibus (GEO). A robust multiarray analysis (RMA) algorithm was applied to detect differentially expressed genes (DEGs). In order to screen for biological pathways and to interrogate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, the database for annotation, visualization, and integrated discovery (DAVID) was used to carry out a gene ontology (GO) function enrichment for DEGs. Finally, a transcriptional regulatory network was constructed, and a hypergeometric distribution test was applied to select for significantly enriched transcriptional factor motifs. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were each up-regulated two-fold in Down syndrome samples compared to normal samples; of these, SON and TTC3 were newly reported. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B, and TTC3 were located on human chromosome 21 (mouse chromosome 16). The DEGs were significantly enriched in macromolecular complex subunit organization and focal adhesion pathways. Eleven significantly enriched transcription factor motifs (PAX5, EGR1, XBP1, SREBP1, OLF1, MZF1, NFY, NFKAPPAB, MYCMAX, NFE2, and RP58) were identified. The DEGs and transcription factor motifs identified in our study provide biomarkers for the understanding of Down syndrome pathogenesis and progression. PMID- 25118626 TI - Pulmonary hypertension due to acute respiratory distress syndrome. AB - Our aims were to describe the prevalence of pulmonary hypertension in patients with acute respiratory distress syndrome (ARDS), to characterize their hemodynamic cardiopulmonary profiles, and to correlate these parameters with outcome. All consecutive patients over 16 years of age who were in the intensive care unit with a diagnosis of ARDS and an in situ pulmonary artery catheter for hemodynamic monitoring were studied. Pulmonary hypertension was diagnosed when the mean pulmonary artery pressure was >25 mmHg at rest with a pulmonary artery occlusion pressure or left atrial pressure <15 mmHg. During the study period, 30 of 402 critically ill patients (7.46%) who were admitted to the ICU fulfilled the criteria for ARDS. Of the 30 patients with ARDS, 14 met the criteria for pulmonary hypertension, a prevalence of 46.6% (95% CI; 28-66%). The most common cause of ARDS was pneumonia (56.3%). The overall mortality was 36.6% and was similar in patients with and without pulmonary hypertension. Differences in patients' hemodynamic profiles were influenced by the presence of pulmonary hypertension. The levels of positive end-expiratory pressure and peak pressure were higher in patients with pulmonary hypertension, and the PaCO2 was higher in those who died. The level of airway pressure seemed to influence the onset of pulmonary hypertension. Survival was determined by the severity of organ failure at admission to the intensive care unit. PMID- 25118627 TI - Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease. AB - Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD. PMID- 25118630 TI - Metabonomic analysis of the therapeutic effect of Potentilla discolor in the treatment of type 2 diabetes mellitus. AB - Type 2 diabetes mellitus (T2DM) is increased worldwide in parallel with the obesity epidemic. Potentilla discolor is one of the most important crude materials in Traditional Chinese medicine (TCM) for therapy of hyperglycemia and hyperlipidemia. In this work, a plasma metabonomic approach based on the combination of UPLC-Q-TOF with multivariate data analysis was applied to investigate the therapeutic effects of the extract of P. discolor (EPD) and corosolic acid (CA), the main bioactive compounds of P. discolor. Male C57BL/6 mice were fed with high-fat diet (HFD-fed group) for 8 weeks and then treated with EPD (EPD-treated group) or CA (CA-treated group) for another 8 weeks. After the experimental period, samples of plasma were collected and analyzed by ultra performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF). The principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models were built to find biomarkers of T2DM and investigate the therapeutic effects of EPD and CA. 26 metabolites, which are distributed in several metabolic pathways, were identified as potential biomarkers of T2DM. It was found that EPD and CA could reverse the pathological process of T2DM through regulating the disturbed pathway of metabolism. The metabonomic results are beneficial not only for the evaluation of the therapeutic effect of TCM but also for the elucidation of the underlying molecular mechanism. PMID- 25118628 TI - Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats. AB - Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease. PMID- 25118631 TI - Prostaglandin E2 levels and platelet function are different in cord blood compared to adults. AB - Neonatal platelets support primary haemostasis and thrombin generation as well as adult platelets, despite observable hypoaggregability in vitro. High prostaglandin E2 levels at accouchement could account for inhibited platelet function via the EP4 receptor. We set out to determine prostaglandin E2 plasma levels in cord blood of healthy neonates and evaluate the impact of prostaglandin E2 on platelet function in adult and cord blood samples. Prostaglandin E2 plasma levels were measured in cord blood and venous adult blood using GC-MS. Impact of prostaglandin E2 on platelet aggregation was measured by spiking cord blood and adult samples. Contributions of EP3 and EP4 receptors were evaluated using respective antagonists. Intracellular cAMP concentrations were measured using a commercial ELISA-kit. Prostaglandin E2 plasma levels were substantially higher in cord blood than in adult samples. Spiking with prostaglandin E2 resulted in a slight but consistent reduction of platelet aggregation in adult blood, but response to PGE2 was blunted in cord blood samples. Aggregation response of spiked adult samples was still higher than with non-spiked cord blood samples. Blockage of EP4 receptors resulted in improved platelet aggregation in adult platelets upon prostaglandin E2 spiking, while aggregation in cord blood samples remained unaltered. Intracellular cAMP concentrations after preincubation with prostaglandin E2 were only increased in adult samples. In conclusion, very high prostaglandin E2 concentrations in cord blood affect platelet function. This effect may partially explain neonatal platelet hypoaggregability. Peak levels of prostaglandin E2 can potentially protect against birth stress-induced platelet activation. PMID- 25118632 TI - Hypnosis for induction of labour. AB - BACKGROUND: Induction of labour using pharmacological and mechanical methods can increase complications. Complementary and alternative medicine methods including hypnosis may have the potential to provide a safe alternative option for the induction of labour. However, the effectiveness of hypnosis for inducing labour has not yet been fully evaluated. OBJECTIVES: To assess the effect of hypnosis for induction of labour compared with no intervention or any other interventions. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2014), handsearched relevant conference proceedings, contacted key personnel and organisations in the field for published and unpublished references. SELECTION CRITERIA: All published and unpublished randomised controlled trials (RCTs) and cluster-RCTs of acceptable quality comparing hypnosis with no intervention or any other interventions, in which the primary outcome is to assess whether labour was induced. DATA COLLECTION AND ANALYSIS: Two review authors assessed the one trial report that was identified (but was subsequently excluded). MAIN RESULTS: No RCTs or cluster-RCTs were identified from the search strategy. AUTHORS' CONCLUSIONS: There was no evidence available from RCTs to assess the effect of hypnosis for induction of labour. Evidence from RCTs is required to evaluate the effectiveness and safety of this intervention for labour induction. As hypnosis may delay standard care (in case standard care is withheld during hypnosis), its use in induction of labour should be considered on a case-by-case basis.Future RCTs are required to examine the effectiveness and safety of hypnotic relaxation for induction of labour among pregnant women who have anxiety above a certain level. The length and timing of the intervention, as well as the staff training required, should be taken into consideration. Moreover, the views and experiences of women and staff should also be included in future RCTs. PMID- 25118633 TI - Pathway deregulation and expression QTLs in response to Actinobacillus pleuropneumoniae infection in swine. AB - Actinobacillus (A.) pleuropneumoniae is among the most important pathogens in pig. The agent causes severe economic losses due to decreased performance, the occurrence of acute or chronic pleuropneumonia, and an increase in death incidence. Since therapeutics cannot be used in a sustainable manner, and vaccination is not always available, new prophylactic measures are urgently needed. Recent research has provided evidence for a genetic predisposition in susceptibility to A. pleuropneumoniae in a Hampshire * German Landrace F2 family with 170 animals. The aim of the present study is to characterize the expression response in this family in order to unravel resistance and susceptibility mechanisms and to prioritize candidate genes for future fine mapping approaches. F2 pigs differed distinctly in clinical, pathological, and microbiological parameters after challenge with A. pleuropneumoniae. We monitored genome-wide gene expression from the 50 most and 50 least susceptible F2 pigs and identified 171 genes differentially expressed between these extreme phenotypes. We combined expression QTL analyses with network analyses and functional characterization using gene set enrichment analysis and identified a functional hotspot on SSC13, including 55 eQTL. The integration of the different results provides a resource for candidate prioritization for fine mapping strategies, such as TF, TFRC, RUNX1, TCN1, HP, CD14, among others. PMID- 25118634 TI - Modelling age-related metabolic disorders in the mouse. AB - Ageing can be characterised by a general decline in cellular function, which affects whole-body homoeostasis with metabolic dysfunction-a common hallmark of ageing. The identification and characterisation of the genetic pathways involved are paramount to the understanding of how we age and the development of therapeutic strategies for combating age-related disease. Furthermore, in addition to understanding the ageing process itself, we must understand the interactions ageing has with genetic variation that results in disease phenotypes. The use of model systems such as the mouse, which has a relatively short lifespan, rapid reproduction (resulting in a large number of offspring), well-characterised biology, a fully sequenced genome, and the availability of tools for genetic manipulation is essential for such studies. Here we review the relationship between ageing and metabolism and highlight the need for modelling these processes. PMID- 25118635 TI - A stem cell medium containing neural stimulating factor induces a pancreatic cancer stem-like cell-enriched population. AB - Cancer stem cells (CSCs) have been studied for their self-renewal capacity and pluripotency, as well as their resistance to anticancer therapy and their ability to metastasize to distant organs. CSCs are difficult to study because their population is quite low in tumor specimens. To overcome this problem, we established a culture method to induce a pancreatic cancer stem-like cell (P CSLC)-enriched population from human pancreatic cancer cell lines. Human pancreatic cancer cell lines established at our department were cultured in CSC inducing media containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), neural cell survivor factor-1 (NSF-1), and N-acetylcysteine. Sphere cells were obtained and then transferred to a laminin-coated dish and cultured for approximately two months. The surface markers, gene expression, aldehyde dehydrogenase (ALDH) activity, cell cycle, and tumorigenicity of these induced cells were examined for their stem cell-like characteristics. The population of these induced cells expanded within a few months. The ratio of CD24high, CD44high, epithelial specific antigen (ESA) high, and CD44variant (CD44v) high cells in the induced cells was greatly enriched. The induced cells stayed in the G0/G1 phase and demonstrated mesenchymal and stemness properties. The induced cells had high tumorigenic potential. Thus, we established a culture method to induce a P-CSLC-enriched population from human pancreatic cancer cell lines. The CSLC population was enriched approximately 100 fold with this method. Our culture method may contribute to the precise analysis of CSCs and thus support the establishment of CSC-targeting therapy. PMID- 25118637 TI - Tavaborole: first global approval. AB - Tavaborole is a novel, low-molecular weight oxaborole antifungal drug under development by Anacor Pharmaceuticals Inc. for the topical treatment of onychomycosis of the toenail. The drug has received its first global approval for this indication in the US. This article summarizes the milestones in the development of tavaborole leading to this first approval for onychomycosis of the toenails. PMID- 25118636 TI - Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor predisposition disorder. AB - Nasal chondromesenchymal hamartoma (NCMH) is a rare nasal tumor that typically presents in young children. We previously reported on NCMH occurrence in children with pleuropulmonary blastoma (PPB), a rare pulmonary dysembryonic sarcoma that is the hallmark neoplasm in the PPB-associated DICER1 tumor predisposition disorder. Original pathologic materials from individuals with a PPB, PPB associated tumor and/or a DICER1 mutation were centrally reviewed by the International PPB Registry. Paraffin-embedded NCMH tumor tissue was available in three cases. Laser-capture microdissection was used to isolate mesenchymal spindle cells and cartilage in one case for Sanger sequencing of DICER1. Nine patients (5F/4M) had PPB and NCMH. NCMH was diagnosed at a median age of 10 years (range 6-21 years). NCMH developed 4.5-13 years after PPB. Presenting NCMH symptoms included chronic sinusitis and nasal congestion. Five patients had bilateral tumors. Local NCMH recurrences required several surgical resections in two patients, but all nine patients were alive at 0-16 years of follow-up. Pathogenic germline DICER1 mutations were found in 6/8 NCMH patients tested. In 2 of the patients with germline DICER1 mutations, somatic DICER1 missense mutations were also identified in their NCMH (E1813D; n = 2). Three additional PPB patients developed other nasal lesions seen in the general population (a Schneiderian papilloma, chronic sinusitis with cysts, and allergic nasal polyps with eosinophils). Two of these patients had germline DICER1 mutations. Pathogenic germline and somatic mutations of DICER1 in NCMH establishes that the genetic etiology of NCMH is similar to PPB, despite the disparate biological potential of these neoplasms. PMID- 25118639 TI - [Subcutaneous emphysema following non-surgical peri-implantitis therapy using an air abrasive device: a case report]. AB - Subcutaneous emphysema are rare complications in periodontology. In most cases, they resolve spontaneously. However, air might disperse into deeper facial spaces causing life-threatening complications such as compression of the tracheobronchial tree or the development of pneumomediastinum. Moreover, microorganisms might spread from the oral cavity into deeper spaces. Hence, rapid diagnosis of subcutaneous emphysema is important. Characteristic signs are both a shiftable swelling and a crepitation. In this case report, the case of a 69-year old man with a subcutaneous emphysema immediately after peri-implantitis therapy with the use of a glycine-based powder air-polishing device is described. Following therapy, air accumulated in the left side of the face. Seven days after non-surgical peri-implantitis therapy, the patient was asymptomatic with complete resolution of the emphysema. PMID- 25118638 TI - Locally-delivered T-cell-derived cellular vehicles efficiently track and deliver adenovirus delta24-RGD to infiltrating glioma. AB - Oncolytic adenoviral vectors are a promising alternative for the treatment of glioblastoma. Recent publications have demonstrated the advantages of shielding viral particles within cellular vehicles (CVs), which can be targeted towards the tumor microenvironment. Here, we studied T-cells, often having a natural capacity to target tumors, for their feasibility as a CV to deliver the oncolytic adenovirus, Delta24-RGD, to glioblastoma. The Jurkat T-cell line was assessed in co-culture with the glioblastoma stem cell (GSC) line, MGG8, for the optimal transfer conditions of Delta24-RGD in vitro. The effect of intraparenchymal and tail vein injections on intratumoral virus distribution and overall survival was addressed in an orthotopic glioma stem cell (GSC)-based xenograft model. Jurkat T cells were demonstrated to facilitate the amplification and transfer of Delta24 RGD onto GSCs. Delta24-RGD dosing and incubation time were found to influence the migratory ability of T-cells towards GSCs. Injection of Delta24-RGD-loaded T cells into the brains of GSC-bearing mice led to migration towards the tumor and dispersion of the virus within the tumor core and infiltrative zones. This occurred after injection into the ipsilateral hemisphere, as well as into the non tumor-bearing hemisphere. We found that T-cell-mediated delivery of Delta24-RGD led to the inhibition of tumor growth compared to non-treated controls, resulting in prolonged survival (p = 0.007). Systemic administration of virus-loaded T cells resulted in intratumoral viral delivery, albeit at low levels. Based on these findings, we conclude that T-cell-based CVs are a feasible approach to local Delta24-RGD delivery in glioblastoma, although efficient systemic targeting requires further improvement. PMID- 25118640 TI - Primary sleeve gastrectomy compared to sleeve gastrectomy as revisional surgery: weight loss and complications at intermediate follow-up. AB - INTRODUCTION: The laparoscopic adjustable gastric band (LAGB) can be revised to sleeve gastrectomy (LSG) for various reasons. Data are limited on the safety and efficacy of single-stage removal of LAGB and creation of LSG. METHODS: A retrospective review of cases was performed from 2010 to 2013. From the primary LSG group, a control group was matched in a 2:1 ratio. RESULTS: Thirty-two patients underwent single-stage revision from LAGB to LSG, with a control group of 64. The most common indication for revision was insufficient weight loss (62.5%). Operative time for revision and control groups was 134 and 92 min, respectively (p < 0.0001). Hospital stay was 3.22 and 2.59 days, respectively (p = 0.02). Overall, the 30-day complication rate for revision and control patients was 14.71 and 6.25%, respectively (p = 0.20). There were no leaks, one stricture (3.13%) in the revision group, and one reoperation for bleeding in the control group (1.56%). For patients with BMI >30 at surgery, change in BMI at 12 months for revision and control was 8.77 and 11.58, respectively (p = 0.02). CONCLUSION: Single-stage revision can be performed safely, with minimal increases in hospital stay and 30-day complications. Weight loss is greater in those who undergo primary LSG compared to those who undergo LSG as revision. PMID- 25118641 TI - Retroperitoneal unicentric Castleman's disease-a hyaline vascular challenge. AB - Castleman's disease is a rare lymphoproliferative disorder. Multiple variants of the disease exist, with differentiation based on tissue pathology and number of masses within the body. We present the medical diagnostic and surgical treatment pathway of a retroperitoneal unicentric hyaline vascular variant complicated by close proximity to major vascular structures. PMID- 25118642 TI - Importance of lymph node involvement in pancreatic neuroendocrine tumors: impact on survival and implications for surgical resection. AB - BACKGROUND: Conflicting data exist on predictors of nodal metastases and their impact on survival in patients with pancreatic neuroendocrine tumors (PNETs). We aim to identify factors associated with lymph node involvement and evaluate the effect of nodal metastases on survival. METHODS: All patients undergoing surgery for PNETs in the Surveillance, Epidemiology, and End Results (SEER) tumor registry from 1988 to 2010 were included. Predictors of lymph node involvement and disease-specific survival (DSS) were evaluated using logistic regression and Cox regression, respectively. RESULTS: Patients (1,915) underwent surgery for a PNET (62% nonfunctional). Nodal positivity was associated with increasing tumor size (p < 0.001) and grade (p < 0.001). Unadjusted DSS at 5 years was 81% for N0, 74 for Nx, and 69% for N1, respectively, (p < 0.001). After adjustment for tumor size and grade, DSS was significantly decreased in N1 patients (HR 1.57; 95% CI 1.23-1.95). For patients who had at least one node examined and had low-grade PNETs <1 cm, no nodal metastases were found. CONCLUSIONS: High tumor grade and increasing size predict nodal metastases in patients with PNETs. N1 status is independently associated with decreased DSS. Low-grade tumors <1 cm may be observed or enucleated. PMID- 25118643 TI - Endoscopy in the early postoperative setting after primary gastrointestinal anastomosis. AB - INTRODUCTION: Gastrointestinal anastomoses may require early evaluation and treatment via flexible endoscopic techniques when complications arise. There is reticence, however, to perform endoscopy given the applied mechanical forces. We aimed to identify the incidence of gastrointestinal anastomotic perforation or disruption resulting from endoscopy performed <=6 weeks of anastomoses. METHODS: Review of patients from 2002 to 2013 who underwent flexible endoscopy within 6 weeks of creation of gastrointestinal anastomosis. Exclusion criteria included intraoperative endoscopy, anastomotic perforation prior to endoscopy, and endoscopy remote from the anastomotic site. Data are presented as median (interquartile range; IQR) or percentages as appropriate. RESULTS: Twenty-four patients met our criteria (age 69 years [IQR 54-77], 54% men]). Endoscopy was performed at a median postoperative time of 18 days (IQR 8-30). Indications for endoscopy included bleeding (66%), obstruction (13%), pain (13%), concern for pancreatic duct leak (4%), and concern for ischemia (4%). Six patients underwent therapeutic endoscopic procedures including coagulation (8%), balloon dilation (8%), tube decompression (8%), and stent placement (4%). There were no anastomotic perforations or disruptions as a result of endoscopy. CONCLUSION: Despite theoretical risks of adverse events of flexible endoscopy in the early postoperative period, no endoscopic perforations or disruptions occurred in recently created surgical anastomoses. PMID- 25118644 TI - Surgeon volume plays a significant role in outcomes and cost following open incisional hernia repair. AB - TITLE: Surgeon Volume Plays a Significant Role in Outcomes and Cost Following Open Incisional Hernia Repair PURPOSE: Incisional hernia is a common complication following gastrointestinal surgery. Many surgeons elect to perform incisional hernia repairs despite performing only limited numbers of hernia repairs annually. This study examines the relationship between surgeon/facility volume and operative time, reoperation rates, and cost following initial open hernia repair. METHODS: The New York Statewide Planning and Research Cooperative System was queried for elective open initial incisional hernias repairs from 2001 to 2006. Surgeon/facility volumes were calculated as mean number of open incisional hernia repairs per year from 2001 to 2006. Reoperations for recurrent hernia over a 5-year period were identified using ICD-9/CPT codes. Multivariable regression was used to compare patient, surgeon, and facility characteristics with operative time, hernia reoperation, and hospital charges. RESULTS: Eighteen thousand forty seven patients met the inclusion criteria. The hernia reoperation rate was 9%, and median time to reoperation was 1.4 years (mean = 1.8). After adjusting for clinical factors, surgeons performing an average of >=36 repairs/year had significantly lower reoperation rates (HR = 0.59, 95% confidence interval (CI) = 0.48,0.72), operative time (incidence rate ratio (IRR) = 0.67, 95% CI = 0.64,0.71), and downstream charges (IRR = 0.63, 95% CI = 0.57,0.69). Facility characteristics (volume, academic affiliation, location) were not associated with reoperation. CONCLUSIONS: This study found a strong association between individual surgeon incisional hernia repair volume and hernia reoperation rates, operative efficiency, and charges. Preferential referral to high-volume surgeons may lead to improved outcomes and lower costs. PMID- 25118647 TI - In silico analysis of different generation beta lactams antibiotics with penicillin binding protein-2 of Neisseria meningitidis for curing meningococcal disease. AB - Neisseria meningitidis is a gram negative, diplococcic pathogen responsible for the meningococcal disease and fulminant septicemia. Penicillin-binding proteins-2 (PBPs) is crucial for the cell wall biosynthesis during cell proliferation of N. meningitidis and these are the target for beta-lactam antibiotics. For many years penicillin has been recognized as the antibiotic for meningococcal disease but the meningococcus has seemed to be antibiotic resistance. In the present work we have verified the molecular interaction of Penicillin binding protein-2 N. meningitidis to different generation of beta-lactam antibiotics and concluded that the third generation of beta-lactam antibiotics shows efficient binding with Penicillin binding protein-2 of N. meningitidis. On the basis of binding efficiency and inhibition constant, ceftazidime emerged as the most efficient antibiotic amongst the other advanced beta-lactam antibiotics against Penicillin binding protein-2 of N. meningitidis. PMID- 25118648 TI - PDB explorer -- a web based algorithm for protein annotation viewer and 3D visualization. AB - The PDB file format, is a text format characterizing the three dimensional structures of macro molecules available in the Protein Data Bank (PDB). Determined protein structure are found in coalition with other molecules or ions such as nucleic acids, water, ions, Drug molecules and so on, which therefore can be described in the PDB format and have been deposited in PDB database. PDB is a machine generated file, it's not human readable format, to read this file we need any computational tool to understand it. The objective of our present study is to develop a free online software for retrieval, visualization and reading of annotation of a protein 3D structure which is available in PDB database. Main aim is to create PDB file in human readable format, i.e., the information in PDB file is converted in readable sentences. It displays all possible information from a PDB file including 3D structure of that file. Programming languages and scripting languages like Perl, CSS, Javascript, Ajax, and HTML have been used for the development of PDB Explorer. The PDB Explorer directly parses the PDB file, calling methods for parsed element secondary structure element, atoms, coordinates etc. PDB Explorer is freely available at http://www.pdbexplorer.eminentbio.com/home with no requirement of log-in. PMID- 25118646 TI - Overexpression of oxidored-nitro domain containing protein 1 induces growth inhibition and apoptosis in human prostate cancer PC3 cells. AB - Previous studies have reported that oxidored-nitro domain containing protein 1 (NOR1) is a novel tumor suppressor gene identified in various types of cancer, such as nasopharyngeal carcinoma and cervical cancer. Recent studies have shown that NOR1 expression is lower in prostate cancer compared with normal prostate tissue. However, the specific function and exact mechanism of NOR1 in prostate cancer remains to be clarified. The present study aimed to investigate the function and mechanism of NOR1 in prostate cancer PC3 cells. DU145 and PC3 cells were transduced with a vector and cell viability, proliferation and apoptosis were determined. As predicted, NOR1 overexpression significantly inhibited growth and apoptosis in PC3 cells. NOR1 overexpression decreased the expression of the anti-apoptotic genes Bcl-2 and Bcl-xl and increased the level of the pro apoptotic genes Bax and Bak in PC3 cells. Further investigation demonstrated that NOR1 overexpression activates caspase-3. Silencing of NOR1 did not inhibit growth or induce apoptosis in PC3 cells. Moreover, NOR1 inhibited proliferation and induced apoptosis via the activation of MAPK. The overexpression of NOR1 significantly inhibited tumor growth in PC3 tumor-bearing nude mice. The results suggest that the upregulated NOR1 expression was able to inhibit the progression of prostate cancer. Thus, NOR1 may be an ideal target for the treatment of prostate cancer. PMID- 25118649 TI - Molecular docking studies of curcumin natural derivatives with DNA topoisomerase I and II-DNA complexes. AB - DNA topoisomerase I (topo I) and II (topo II) are essential enzymes that solve the topological problems of DNA by allowing DNA strands or double helices to pass through each other during cellular processes such as replication, transcription, recombination, and chromatin remodeling. Their critical roles make topoisomerases an attractive drug target against cancer. The present molecular docking study provides insights into the inhibition of topo I and II by curcumin natural derivatives. The binding modes suggested that curcumin natural derivatives docked at the site of DNA cleavage parallel to the axis of DNA base pairing. Cyclocurcumin and curcumin sulphate were predicted to be the most potent inhibitors amongst all the curcumin natural derivatives docked. The binding modes of cyclocurcumin and curcumin sulphate were similar to known inhibitors of topo I and II. Residues like Arg364, Asn722 and base A113 (when docked to topo I-DNA complex) and residues Asp479, Gln778 and base T9 (when docked to topo II-DNA complex) seem to play important role in the binding of curcumin natural derivatives at the site of DNA cleavage. PMID- 25118650 TI - Mis-sesnse mutations in Tafazzin (TAZ) that escort to mild clinical symptoms of Barth syndrome is owed to the minimal inhibitory effect of the mutations on the enzyme function: In-silico evidence. AB - Tafazzin (EC 2.3.1.23) is a Phospholipid Transacylase involved in Cardiolipin remodeling on mitochondrial membrane and coded by TAZ gene (Cytogenetic Location: Xq28) in human. Its mutations cause Barth syndrome (MIM ID: #302060)/3-Methyl Glutaconyl Aciduria Type II, an inborn error of metabolism often leading to foetal or infantile fatality. Nevertheless, some mis-sense mutations result in mild clinical symptoms. To evaluate the rationale of mild symptoms and for an insight of Tafazzin active site, sequence based and structure based ramifications of wild and mutant Tafazzins were compared in-silico. Sequence based domain predictions, surface accessibilities on substitution & conserved catalytic sites with statistical drifts, as well as thermal stability changes for the mutations and the interaction analysis of Tafazzin were performed. Crystal structure of Tafazzin is not yet resolved experimentally, therefore 3D coordinates of Tafazzin and its mutants were spawned through homology modeling. Energetically minimized and structurally validated models were used for comparative docking simulations. We analyzed active site geometry of the models in addition to calculating overall substrate binding efficiencies for each of the enzyme-ligand complex deduced from binding energies instead of comparing only the docking scores. Also, individual binding energies of catalytic residues on conserved HX4D motif of Acyltransferase superfamily present in Tafazzins were estimated. This work elucidates the basis of mild symptoms in patients with mis-sense mutations, identifies the most pathogenic mutant among others in the study and also divulges the critical role of HX4D domain towards successful transacylation by Taffazin. The in-silico observations are in complete agreement with clinical findings reported for the patients with mutations. PMID- 25118651 TI - An enzoinformatics study for prediction of efficacies of three novel penem antibiotics against New Delhi metallo-beta-lactamase-1 bacterial enzyme. AB - New Delhi metallo-beta-lactamase (NDM-1) is a beta-lactamase (class B carbapenemase) containing Zn2+ and other divalent cations as cofactors which possesses the ability to inactivate all beta lactams (including carbapenems) except aztreonam by catalyzing the hydrolytic cleavage of the substrate amide bond. Carbapenemases are either serine enzymes or metallo-beta-lactamases (MBLs) that utilize at least one zinc ion for hydrolysis. The present study describes the molecular interaction of carbapenems (Imipenem, Meropenem, Ertapenem, Doripenem, Panipenem, Biapenem, Razupenem, Faropenem, Tebipenem and Tomopenem) with NDM-1, beta-lactamase enzyme. Docking between NDM-1 and each of these carbapenems (separately) was performed using 'Autodock4.2'. PMID- 25118645 TI - The burden of HPV-associated anogenital cancers. AB - The epidemiology of anogenital cancers is under going substantial change. Cervical cancer remains a major public health concern, particular in resource limited settings. Cancers of the anus, penis, vagina and vulva are relatively uncommon cancers, but may be increasing in incidence. The change in occurrence of anogenital cancers may be due to increasing HPV transmission secondary to changes in sexual behaviour. Screening programmes and the HPV vaccine offer optimism that anogenital cancers can be prevented. This article reviews the epidemiology of anogenital cancers with a focus on Scottish data. PMID- 25118652 TI - Performance evaluation of Warshall algorithm and dynamic programming for Markov chain in local sequence alignment. AB - Markov Chain is very effective in prediction basically in long data set. In DNA sequencing it is always very important to find the existence of certain nucleotides based on the previous history of the data set. We imposed the Chapman Kolmogorov equation to accomplish the task of Markov Chain. Chapman Kolmogorov equation is the key to help the address the proper places of the DNA chain and this is very powerful tools in mathematics as well as in any other prediction based research. It incorporates the score of DNA sequences calculated by various techniques. Our research utilize the fundamentals of Warshall Algorithm (WA) and Dynamic Programming (DP) to measures the score of DNA segments. The outcomes of the experiment are that Warshall Algorithm is good for small DNA sequences on the other hand Dynamic Programming are good for long DNA sequences. On the top of above findings, it is very important to measure the risk factors of local sequencing during the matching of local sequence alignments whatever the length. PMID- 25118653 TI - In silico analysis for five major cereal crops phytocystatins. AB - Five major cereal crops like rice, wheat, maize, barley and sorghum are continuously threatened by a multitude of pathogens and other disorders. Cystatins offers a pivotal role in deciding the promising plant response. The use of bioinformatics tools for phylogenetic relationships of five major cereal crops (rice, wheat, maize, barley and sorghum) phytocystatins based on amino acid sequence information was elucidated and their secondary and tertiary structures were investigated for structural comparisons. Twenty eight distinct phytocystatins from 28 plant species were investigated. Phytocystatins could be divided into five distinct phylogenetic groups. Five major cereal crops their structural features were highly conserved their amino acid sequence similarities ranged from 48 to 86%. A new highly conserved amino acid sequence motif, YEAKxWxKxF, in the C-terminal end being unique to phytocystatins was identified. The predicted 3D homology models showed a high conservation of the general central structure of the phytocystatins i.e. the 4-5 anti-parallel beta-sheets, wrapping halfway round a single central alpha-helix and particularly the three active site regions, the N-terminal, the 1st and 2nd hairpin loops. Any structural differences seem to be mainly in the length of the N and C terminal, the length of the 2nd hairpin loop and the 5th beta-sheet. Via docking experiments, small heterogeneities were observed in the vicinity of the OC-I active sites that seemed to be influential in the binding process and stability of the resultant inhibitor-protease complex. PMID- 25118654 TI - Effects of bridge functions on radial distribution functions of liquid water. AB - In this report the radial distribution functions (RDFs) of liquid water are calculated on the basis of the classical density functional theory combined with the reference interaction site model for molecular liquids. The bridge functions, which are neglected in the hypernetted-chain (HNC) approximation, are taken into account through the density expansion for the Helmholtz free energy functional up to the third order. A factorization approximation to the ternary direct correlation functions in terms of the site-site pair correlation functions is then employed in the expression of the bridge functions, thus leading to a closed set of integral equations for the determination of the RDFs. It is confirmed through numerical calculations that incorporation of the oxygen-oxygen bridge function substantially improves the poor descriptions by the HNC approximation at room temperature, e.g., for the second peak of the oxygen-oxygen RDF. PMID- 25118656 TI - {RuNO}(6)vs. co-ligand oxidation: two non-innocent groups in one ruthenium nitrosyl complex. AB - Recently, a new {RuNO}(6) complex, [Ru(L)(PPh3)(NO)(Cl)](2+) (where L = 1-phenyl 1-(pyridin-2-yl)-2-(pyridin-2-ylmethylene)hydrazine), was reported which exhibits a one-electron quasireversible oxidation. The oxidized product, [Ru(L)(PPh3)(NO)(Cl)](3+), was isolated and proposed to be a highly unusual {RuNO}(5) complex. In this paper, we investigate the electronic structure of both of these ruthenium complexes by DFT calculations and find that the oxidized species is best described as a {RuNO}(6) complex with a co-ligand radical. [Ru(L)(PPh3)(NO)(Cl)](2+) is therefore oxidized to [Ru(L(+))(PPh3)(NO)(Cl)](3+), i.e. this is an interesting example of a complex with two non-innocent ligands simultaneously bound to a ruthenium center. PMID- 25118657 TI - Does guideline knowledge affect treatment compliance among emergency doctors? AB - BACKGROUND: The insufficient adoption of internationally accepted clinical guidelines may lead to less than adequate patient care of patients with asthma. OBJECTIVE: To evaluate the knowledge and treatment compliance with Global Initiative of Asthma (GINA, 2011) asthma treatment guidelines among emergency physicians (EPs) at a referral hospital in northern Malaysia. METHODS: A cross sectional study was designed in the territory-level referral hospital in northern Malaysia. Twenty-seven EPs were asked to complete an asthma guideline questionnaire to assess their knowledge regarding GINA 2011 asthma treatment guidelines. A total of 810 patients were enrolled, and 30 patients were selected per physician. The authors evaluated the physicians' compliance with GINA 2011 asthma treatment guidelines. RESULTS: Of 27 EPs, 20 (74.1%) had adequate knowledge of GINA 2011 asthma treatment guidelines. A total of 615 (75.9%) patients received guideline-recommended emergency treatment. Shortness of breath (n = 436, 53.8%) was the most frequently reported chief complaint. Furthermore, there was a significant but weak association between knowledge of the guideline and treatment compliance among emergency doctors (P = 0.003, phi = 0.110). Moreover, there was no significant change in therapy for patients with comorbid conditions. The mean age of respondents was 27.3 years. CONCLUSIONS: Overall, a fair level of guideline knowledge and treatment compliance was noted among EPs. Doctors with adequate guideline knowledge were more likely to comply with GINA 2011 asthma treatment guidelines. PMID- 25118655 TI - Identification and characterization of alkaline protease producing Bacillus firmus species EMBS023 by 16S rRNA gene sequencing. AB - Probiotic microorganisms are those which exert a positive exect on the growth of the host, when administered as a dietary mixture in an adequate amount. They form the best alternative to the use of antibiotics for controlling enteric diseases in poultry farm animals, especially in the light of the gruesome problems of development of antibiotic resistance in enteric pathogens and the contamination of poultry products with antibiotics. 16S rDNA sequencing which has gained wide popularity amongst microbiologists for the molecular characterization and identification of newly discovered isolates provides accurate identification of isolates down to the level of sub-species (strain). It's most important advantage over the traditional biochemical characterization methods are that it can provide an accurate identification of strains with atypical phenotypic characters as well. The following work is an application of 16S rRNA gene sequencing approach to identify a novel, alkaline protease producing bacteria, from poultry farm waste. The sample was collected from a local poultry farm in the Guntur district, Andhra Pradesh, India. Subsequently the sample was serially diluted and the aliquots were incubated for a suitable time period following which the suspected colony was subjected to 16S rDNA sequencing. The results showed the isolate to be a novel, high alkaline protease producing bacteria, which was named Bacillus firmus isolate EMBS023, after characterization the sequence of isolate was deposited in GenBank with accession number JN990980. PMID- 25118658 TI - Physiological measurements using ultra-high field fMRI: a review. AB - Functional MRI (fMRI) has grown to be the neuroimaging technique of choice for investigating brain function. This topical review provides an outline of fMRI methods and applications, with a particular emphasis on the recent advances provided by ultra-high field (UHF) scanners to allow functional mapping with greater sensitivity and improved spatial specificity. A short outline of the origin of the blood oxygenation level dependent (BOLD) contrast is provided, followed by a review of BOLD fMRI methods based on gradient-echo (GE) and spin echo (SE) contrast. Phase based fMRI measures, as well as perfusion contrast obtained with the technique of arterial spin labelling (ASL), are also discussed. An overview of 7 T based functional neuroimaging is provided, outlining the potential advances to be made and technical challenges to be addressed. PMID- 25118659 TI - 1-calcium phosphate-uracil, a synthesized pyrimidine derivative agent, has anti proliferative, pro-apoptotic and anti-invasion effects on multiple tumor cell lines. AB - 1-calcium phosphate-uracil (1-CP-U), a synthetic pyrimidine derivative, has been documented to demonstrate a variety of different biological activities. However, the potency and mechanisms of this agent's anti-cancer activity have not been elucidated to date. In the present study, the anti-cancer effects of 1-CP-U were examined in a range of in vitro assays. Different cell lines were treated with 1 CP-U at varied concentrations (0.7, 1.0, 1.4 umol/l) for indicated durations. The cell proliferation was then examined by MTT assay. The cellular apoptotic effects were detected by Hoechst 33342 and Annexin V/propidium iodide staining, while the capacity of 1-CP-U on invasion and migration were examined by cell invasion and wound healing assays. The expression of matrix metalloproteinase proteins, as well as pro- and antiapoptotic proteins was detected by western blotting analysis. The results identified that 1-CP-U was able to inhibit the viability of SKOV3, HeLa, SMMC-7721 and A549 cell lines in a dose- and time-dependent manner, while it exerted only marginal toxic effects on non-cancerous cells. The IC50 concentration of 1-CP-U for tumor cell lines was ~1.0 umol/l. The growth inhibition induced by 1-CP-U was accompanied by a broad spectrum of pro-apoptotic activities, in which different cell lines varied in their sensitivity to 1-CP-U. Meanwhile, the increased expression of the pro-apoptotic protein B-cell lymphoma 2 (Bcl-2)-associated X and a marked reduction of Bcl-2 levels were associated with increased 1-CP-U concentrations. Additionally, anti-migration and anti invasion effects of 1-CP-U were evidently associated with the downregulation of matrix metalloproteinase proteins. Of note, it was observed that 1-CP-U significantly inhibited both the migration and invasion at a lower concentration, as compared with the dose required to achieve significant inhibition of apoptosis. These results indicated that 1-CP-U appeared to be a more effective inhibitor of cell migration and invasion, rather than of apoptosis. In conclusion, the present study was the first, to the best of our knowledge, to demonstrate the function of 1-CP-U in tumor proliferation, apoptosis and invasion with specific effects against cancer cells in vitro, suggesting 1-CP-U as a potential novel anticancer agent. PMID- 25118660 TI - Physical and sexual abuse and early-onset bipolar disorder in youths receiving outpatient services: frequent, but not specific. AB - The objective of this study was to determine if physical and sexual abuse showed relationships to early-onset bipolar spectrum disorders (BPSD) consistent with findings from adult retrospective data. Participants (N = 829, M = 10.9 years old +/- 3.4 SD, 60% male, 69% African American, and 18% with BPSD), primarily from a low socio-economic status, presented to an urban community mental health center and a university research center. Physical abuse was reported in 21%, sexual abuse in 20%, and both physical and sexual abuse in 11% of youths with BPSD. For youths without BPSD, physical abuse was reported in 16%, sexual abuse in 15%, and both physical and sexual abuse in 5% of youths. Among youth with BPSD, physical abuse was significantly associated with a worse global family environment, more severe depressive and manic symptoms, a greater number of sub-threshold manic/hypomanic symptoms, a greater likelihood of suicidality, a greater likelihood of being diagnosed with PTSD, and more self-reports of alcohol or drug use. Among youth with BPSD, sexual abuse was significantly associated with a worse global family environment, more severe manic symptoms, a greater number of sub-threshold manic/hypomanic symptoms, greater mood swings, more frequent episodes, more reports of past hospitalizations, and a greater number of current and past comorbid Axis I diagnoses. These findings suggest that if physical and/or sexual abuse is reported, clinicians should note that abuse appears to be related to increased severity of symptoms, substance use, greater co-morbidity, suicidality, and a worse family environment. PMID- 25118661 TI - Effect of DTPP-mediated photodynamic therapy on cell morphology, viability, cell cycle, and cytotoxicity in a murine lung adenocarcinoma cell line. AB - Photodynamic therapy (PDT) involves the administration and activation of photosensitizing reagents in cancer tissues to induce cytotoxicity. Here we examined the effects of 5-5- (4-N, N-diacetoxylphenyl)-10,15,20- tetraphenylporphyrin (DTPP) -mediated PDT on cell morphology, viability, cell cycle, and cytotoxicity in a murine lung adenocarcinoma cell line. LA795 murine lung adenocarcinoma cell line was used in the study, with cellular uptake of DTPP being quantified by a UV-visible spectrophotometer. The subcellular localization of DTPP was detected by confocal laser scanning microscopy, alteration of cell morphology after PDT was observed by an inverted light microscope, and late-stage apoptosis was examined by terminal dUTP nick end labeling (TUNEL) . The effects of influencing factors on cytotoxicity of PDT in LA795 cells was investigated with varying concentrations of DTPP, energy densities, power densities, and antioxidants by 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Effects of PDT on cell cycle and plasma membrane integrity were studied by flow cytometry analysis. The uptake of DTPP by LA795 cells reached maximum after incubation for 24 h. Confocal laser scanning microscopy showed that DTPP was mainly in the mitochondrion, and slight localization was detected in the lysosomes. Cellular inhibitory effects increased with increased irradiation dose and DTPP concentration, while unactivated DTPP had low toxicity. Flow cytometry analysis revealed that DTPP-PDT-treated cells showed S phase arrest. Cell membrane damage initiation, repair, and irreversible damage were observed at 2, 4, and 5 h after DTPP-PDT , respectively. Together, our results demonstrated cell apoptosis, compromised viability, and cell cycle S phase arrest of LA795 in response to DTPP-PDT , while no effect on the lung cancer cells was observed with irradiation or photosensitizer treatment alone. PMID- 25118662 TI - Early detection of dental fluorosis using Raman spectroscopy and principal component analysis. AB - Raman spectroscopic technique has the potential to provide vibrational spectra of minerals by analyzing scattered light caused by monochromatic laser excitation. In this paper, recent applications of Raman spectroscopy in the study of dental hard tissues are reported. Special attention is given to mineral components in enamel and to calcium fluoride formed in/on enamel. The criteria used to classify the dental hard samples were according to the Dean Index (DI), which consists into healthy or control, mild, moderate, and severe, indicating the amount of dental fluorosis observed on enamel. A total of 39 dental samples (9 control, 9 mild, 10 moderate, and 11 severe) were analyzed in the study. Dental samples were positioned under an Olympus microscope, and around 10 points were chosen for Raman measurement. All spectra were collected by a Horiba Jobin-Yvon LabRAM HR800 Raman Spectrometer with a laser of 830-nm and 17-mW power irradiation. Raw spectra were processed by carrying out baseline correction, smoothing, and normalization to remove noise, florescence, and shot noise and then analyzed using principal component analysis (PCA). In the spectra of dental samples, we observed the main bands as the broad band due to CO[Formula: see text] (240-300 cm (-1)), CaF 2 (322 cm (-1)), PO[Formula: see text] vibrations (437 and 450 cm ( 1)), PO[Formula: see text] vibrations (582, 598, and 609 cm (-1)), PO[Formula: see text] vibrations (960 cm (-1)), PO[Formula: see text] vibrations (1,045 cm ( 1)), and CO[Formula: see text] vibration (1,073 cm (-1)). Nevertheless, the intensity of the band at 960 cm (-1) associated to symmetric stretch of phosphate, PO[Formula: see text], decreases as the amount of dental fluorosis increases, suggesting that the intensity of this band could be used to quantitatively measure the level of fluorosis on a dental sample. On the other hand, PCA allowed to identify two large clusters discriminating between control, and severe and moderate samples with high sensitivity and specificity. PCA was able to discriminate mild from moderate samples with 100 % sensitivity and 89 % specificity and mild from severe samples with 91 % sensitivity and 100 % specificity. In addition, PCA was also able to discriminate between mild samples and group formed by the moderate and severe samples with 95 % sensitivity and 89 % specificity. Finally, PCA allowed us to define the wavelength differences between the spectral bands of the healthy teeth with sound enamel and those with fluorosis by confirming that the main chemical differences among control and severe fluorosis samples were associated to the vibrational modes of phosphate (PO[Formula: see text], PO[Formula: see text], PO[Formula: see text], and PO[Formula: see text] and carbonate (CO[Formula: see text]) ions. The preliminary results suggest that Raman-PCA technique has the potential to be a noninvasive real-time tool for the early detection and monitoring evolution of dental fluorosis. PMID- 25118663 TI - Are the mitochondrial respiratory complexes blocked by NO the targets for the laser and LED therapy? AB - Effects of laser (442 and 532 nm) and light-emitting diode (LED) (650 nm) radiation on mitochondrial respiration and mitochondrial electron transport rate (complexes II-III and IV) in the presence of nitric oxide (NO) were investigated. It was found that nitric oxide (300 nM-10 MUM) suppresses mitochondrial respiration. Laser irradiation of mitochondria (442 nm, 3 J cm(-2)) partly restored mitochondrial respiration (approximately by 70 %). Irradiation with green laser (532 nm) or red LED (650 nm) in the same dose had no reliable effect. Evaluation of mitochondrial electron transport rate in complexes II-III and IV and effects of nitric oxide demonstrated almost similar sensitivity of complex II III and IV to NO, with approximately 50 % inhibition at NO concentration of 3 MUM. Subsequent laser or LED irradiation (3 J cm(-2)) showed partial recovery of electron transport only in complex IV and only under irradiation with blue light (442 nm). Our results support the hypothesis of the crucial role of cytochrome c oxidase (complex IV) in photoreactivation of mitochondrial respiration suppressed by NO. PMID- 25118664 TI - Effect of different surface treatments on the microtensile bond strength of two self-adhesive flowable composites. AB - The aim of this study was to evaluate the effect of different surface treatments on the microtensile bond strength (MUTBS) of two different self-adhesive flowable composite materials (SACs) to dentin. Forty extracted human molars were horizontally flattened to expose the dentin surfaces. The teeth were divided into eight groups according to the surface treatments (acid etching, Er:YAG laser quantum square pulse (QSP) mode, and Er:YAG laser medium-short pulse (MSP) mode at 10 Hz, 1.2 W, 120 mJ, and control-SiC) and SAC type (Vertise Flow and Fusio Liquid Dentin) (n = 5). Light cured 4-mm-high composite build-ups were made on the dentin surfaces, and the specimens were sectioned into serial sticks (n = 15). Later, the specimens were attached to microtensile testing machine and tensile force was applied at a crosshead speed of 1 mm/min until failure occurred. The failure modes were evaluated using a stereomicroscope at *40 magnification, and one sample from each group was used for scanning electron microscopy (SEM) evaluation. The data were analyzed with two-way ANOVA and Tukey's HSD test (alpha = 0.05). In all surface treatment groups along with the control groups, Vertise Flow showed better MUTBS than the Fusio Liquid Dentin with the exception of the Er:YAG MSP mode surface treatment (p < 0.05). Etching with phosphoric acid and the Er:YAG QSP mode surface treatment significantly increased the MUTBS of Vertise Flow (p < 0.05). Etching with phosphoric acid, Er:YAG QSP mode surface treatment, and Er:YAG MSP mode surface treatment significantly increased the MUTBS of Fusio Liquid Dentin (p < 0.05). The MUTBS of Vertise Flow was higher than the MUTBS of Fusio Liquid Dentin. The Er:YAG laser irradiation increased the MUTBS of both self-adhesive flowable resin composites in two pulse modes tested (MSP or QSP). However, the highest MUTBS was recorded when Vertise Flow was applied with acid etching. PMID- 25118665 TI - Electrocardiogram derived respiratory rate from QRS slopes and R-wave angle. AB - A method for estimating respiratory rate from electrocardiogram (ECG) signals is presented. It is based on QRS slopes and R-wave angle, which reflect respiration induced beat morphology variations. The 12 standard leads, 3 leads from vectorcardiogram (VCG), and 2 additional non-standard leads derived from VCG loops were analyzed. The following series were studied as ECG derived respiration (EDR) signals: slope between the peak of Q and R waves, slope between the peak of R and S waves, and the R-wave angle. Information from several EDR signals was combined in order to increase the robustness of estimation. Evaluation is performed over two databases containing ECG and respiratory signals simultaneously recorded during two clinical tests with different characteristics: tilt test, representing abrupt cardiovascular changes, and stress test representing a highly non-stationary and noisy environment. A combination of QRS slopes and R-wave angle series derived from VCG leads obtained a respiratory rate estimation relative error of 0.50 +/- 4.11% (measuring 99.84% of the time) for tilt test and 0.52 +/- 8.99% (measuring 96.09% of the time) for stress test. These results outperform those obtained by other reported methods, both in tilt and stress testing. PMID- 25118666 TI - Modeling of the acute effects of primary hypertension and hypotension on the hemodynamics of intracranial aneurysms. AB - Hemodynamics is a risk factor in intracranial aneurysms (IA). Hypertension and pharmacologically induced hypotension are common in IA patients. This study investigates how hypertension and hypotension may influence aneurysmal hemodynamics. Images of 23 IAs at typical locations were used to build patient specific Computational Fluid Dynamics models. The effects of hypotension and hypertension were simulated through boundary conditions by modulating the normotensive flow and pressure waveforms, in turn produced by a 1D systemic vascular model. Aneurysm location and flow pattern types were used to categorize the influence of hypotension and hypertension on relevant flow variables (velocity, pressure and wall shear stress). Results indicate that, compared to other locations, vertebrobasilar aneurysms (VBA) are more sensitive to flow changes. In VBAs, space-averaged velocity at peak systole increased by 30% in hypertension (16-21% in other locations). Flow in VBAs in hypotension decreased by 20% (10-13% in other locations). Momentum-driven hemodynamic types were also more affected by hypotension and hypertension, than shear-driven types. This study shows how patient-specific modeling can be effectively used to identify location-specific flow patterns in a clinically-relevant study, thus reinforcing the role played by modeling technologies in furthering our understanding of cardiovascular disease, and their potential in future healthcare. PMID- 25118667 TI - Development of a 10-year-old full body geometric dataset for computational modeling. AB - The objective of this study was to create a computer-aided design (CAD) geometric dataset of a 10-year-old (10 YO) child. The study includes two phases of efforts. At Phase One, the 10 YO whole body CAD was developed from component computed tomography and magnetic resonance imaging scans of 12 pediatric subjects. Geometrical scaling methods were used to convert all component parts to the average size for a 10 YO child, based on available anthropometric data. Then the component surfaces were compiled and integrated into a complete body. The bony structures and flesh were adjusted as symmetrical to minimize the bias from a single subject while maintaining anthropometrical measurements. Internal organs including the liver, spleen, and kidney were further verified by literature data. At Phase Two, internal characteristics for the cervical spine disc, wrist, hand, pelvis, femur, and tibia were verified with data measured from additional 94 10 YO children. The CAD dataset developed through these processes was mostly within the corridor of one standard deviation (SD) of the mean. In conclusion, a geometric dataset for an average size 10 YO child was created. The dataset serves as a foundation to develop computational 10 YO whole body models for enhanced pediatric injury prevention. PMID- 25118668 TI - Accuracy and reproducibility of patient-specific hemodynamic models of stented intracranial aneurysms: report on the Virtual Intracranial Stenting Challenge 2011. AB - Validation studies are prerequisites for computational fluid dynamics (CFD) simulations to be accepted as part of clinical decision-making. This paper reports on the 2011 edition of the Virtual Intracranial Stenting Challenge. The challenge aimed to assess the reproducibility with which research groups can simulate the velocity field in an intracranial aneurysm, both untreated and treated with five different configurations of high-porosity stents. Particle imaging velocimetry (PIV) measurements were obtained to validate the untreated velocity field. Six participants, totaling three CFD solvers, were provided with surface meshes of the vascular geometry and the deployed stent geometries, and flow rate boundary conditions for all inlets and outlets. As output, they were invited to submit an abstract to the 8th International Interdisciplinary Cerebrovascular Symposium 2011 (ICS'11), outlining their methods and giving their interpretation of the performance of each stent configuration. After the challenge, all CFD solutions were collected and analyzed. To quantitatively analyze the data, we calculated the root-mean-square error (RMSE) over uniformly distributed nodes on a plane slicing the main flow jet along its axis and normalized it with the maximum velocity on the slice of the untreated case (NRMSE). Good agreement was found between CFD and PIV with a NRMSE of 7.28%. Excellent agreement was found between CFD solutions, both untreated and treated. The maximum difference between any two groups (along a line perpendicular to the main flow jet) was 4.0 mm/s, i.e. 4.1% of the maximum velocity of the untreated case, and the average NRMSE was 0.47% (range 0.28-1.03%). In conclusion, given geometry and flow rates, research groups can accurately simulate the velocity field inside an intracranial aneurysm-as assessed by comparison with in vitro measurements-and find excellent agreement on the hemodynamic effect of different stent configurations. PMID- 25118669 TI - Improvement of biodegradability, bioactivity, mechanical integrity and cytocompatibility behavior of biodegradable mg based orthopedic implants using nanostructured Bredigite (Ca7MgSi 4O 16) bioceramic coated via ASD/EPD technique. AB - This research explored the influence of surface modification of AZ91 Mg alloy on the biodegradation, bioactivity, mechanical integrity and cytocompatibility of the alloy. For this purpose, a nanostructured bredigite (Ca7MgSi4O16) ceramic coating was prepared on biodegradable AZ91 Mg alloy through anodic spark deposition and electrophoretic deposition method. The phase composition and surface morphology of the coated alloy were characterized by X-ray diffraction, scanning electron microscope and transmission electron microscope. The properties of samples were investigated by electrochemical measurements, immersion test, compression examination and cell culturing. The results showed that the degradation resistance, bioactivity, mechanical integrity and cytocompatibility of biodegradable Mg alloy were improved by the anodic spark deposition and electrophorretic deposition of the nanostructured bredigite coating. Therefore, the nanostructured bredigite ceramic coating is identified as a good coating for AZ91 Mg alloy for the purpose of making biodegradable metallic orthopedic implants. PMID- 25118670 TI - Permeability analysis of neuroactive drugs through a dynamic microfluidic in vitro blood-brain barrier model. AB - This paper presents the permeability analysis of neuroactive drugs and correlation with in vivo brain/plasma ratios in a dynamic microfluidic blood brain barrier (BBB) model. Permeability of seven neuroactive drugs (Ethosuximide, Gabapentin, Sertraline, Sunitinib, Traxoprodil, Varenicline, PF-304014) and trans endothelial electrical resistance (TEER) were quantified in both dynamic (microfluidic) and static (transwell) BBB models, either with brain endothelial cells (bEnd.3) in monoculture, or in co-culture with glial cells (C6). Dynamic cultures were exposed to 15 dyn/cm(2) shear stress to mimic the in vivo environment. Dynamic models resulted in significantly higher average TEER (respective 5.9-fold and 8.9-fold increase for co-culture and monoculture models) and lower drug permeabilities (average respective decrease of 0.050 and 0.052 log(cm/s) for co-culture and monoculture) than static models; and co-culture models demonstrated higher average TEER (respective 90 and 25% increase for static and dynamic models) and lower drug permeability (average respective decrease of 0.063 and 0.061 log(cm/s) for static and dynamic models) than monoculture models. Correlation of the resultant logP e values [ranging from 4.06 to -3.63 log(cm/s)] with in vivo brain/plasma ratios (ranging from 0.42 to 26.8) showed highly linear correlation (R (2) > 0.85) for all model conditions, indicating the feasibility of the dynamic microfluidic BBB model for prediction of BBB clearance of pharmaceuticals. PMID- 25118672 TI - Parasitization of juvenile edible crabs (Cancer pagurus) by the dinoflagellate, Hematodinium sp.: pathobiology, seasonality and its potential effects on commercial fisheries. AB - This study reports on the prevalence and severity of infections caused by the parasitic dinoflagellate, Hematodinium in juvenile edible crabs (Cancer pagurus) found in 2 intertidal survey sites (Mumbles Head and Oxwich Bay) in the Bristol Channel, UK. Crabs were assessed for the presence and severity of Hematodinium infections by the histological examination of infected tissues. Such infections were found to exhibit a seasonal trend in the 2 study areas with high numbers of animals (ca. 30%) infected in the spring to summer but with low severity. Conversely, in November only ca. 10% of crabs were infected but these animals had large numbers of parasites in their haemolymph and other tissues. At this time, the carapace and underlying tissues of infected crabs had the chalky, pinkish orange appearance that is characteristic of this disease. Hematodinium-infected crabs ranged in size from 12 to 74 mm carapace width. Overall, it is concluded that the high prevalence of infection of juvenile crabs in this area may have implications for the sustainability of the edible crab fishery in the Bristol Channel. PMID- 25118673 TI - Recent patents on calcium channel blockers: emphasis on CNS diseases. AB - INTRODUCTION: Altered homeostasis of cell calcium movement is a central stage in multiple diseases of CNS. This explains the great therapeutic interest in blockers for the various subtypes of voltage-activated calcium channels (VACCs) expressed in neurons. Mitigation of Ca(2+) entry excess elicited by those blockers may restore the altered synaptic transmission, synaptic plasticity and gene expression to normal parameters, ending the enhanced neuronal vulnerability. AREAS COVERED: This review summarize 23 patents on ligands for L-, N- or T-type channels, claimed to have potential therapeutic interest in epilepsy, pain, migraine and neurodegenerative diseases. EXPERT OPINION: Collections of compounds are generally screened in cell lines expressing a given subtype of VACCs. IC50 to block such channels are often, but not always, provided. In few instances, compounds exhibiting the highest potency in in vitro experiments are also tested in animal models of pain, behavior, epilepsy or Alzheimer's disease. Attempts to develop selectivity for a given VACC subtype with non-peptidic organic ligands have so far failed. Due to their wide tissue expression, such selectivity is crucial for minimizing possible side effects. However, the few data reported by patents does not allow prediction of selectivity of the new compounds in many cases. PMID- 25118671 TI - Characterization of abnormal wall shear stress using 4D flow MRI in human bicuspid aortopathy. AB - There exists considerable controversy surrounding the timing and extent of aortic resection for patients with BAV disease. Since abnormal wall shear stress (WSS) is potentially associated with tissue remodeling in BAV-related aortopathy, we propose a methodology that creates patient-specific 'heat maps' of abnormal WSS, based on 4D flow MRI. The heat maps were created by detecting outlier measurements from a volumetric 3D map of ensemble-averaged WSS in healthy controls. 4D flow MRI was performed in 13 BAV patients, referred for aortic resection and 10 age-matched controls. Systolic WSS was calculated from this data, and an ensemble-average and standard deviation (SD) WSS map of the controls was created. Regions of the individual WSS maps of the BAV patients that showed a higher WSS than the mean + 1.96SD of the ensemble-average control WSS map were highlighted. Elevated WSS was found on the greater ascending aorta (35% +/- 15 of the surface area), which correlated significantly with peak systolic velocity (R (2) = 0.5, p = 0.01) and showed good agreement with the resected aortic regions. This novel approach to characterize regional aortic WSS may allow clinicians to gain unique insights regarding the heterogeneous expression of aortopathy and may be leveraged to guide patient-specific resection strategies for aorta repair. PMID- 25118675 TI - Common Mental Disorders at the Time of Deportation: A Survey at the Mexico-United States Border. AB - Deportations from the Unites States (US) to Mexico increased substantially during the last decade. Considering deportation as a stressful event with potential consequences on mental health, we aimed to (1) estimate the prevalence of common mental disorders (CMD) among deported migrants; and (2) explore the association between migratory experience, social support and psychological variables, and CMD in this group. In repatriation points along the border, a probability sample of deportees responded to the Self Reporting Questionnaire (SRQ). The prevalence of CMD was 16.0% (95% CI 12.3, 20.6). There was a U-shaped association between time in the US and SRQ score. Times returned to Mexico, having a spouse in the US, number of persons in household, less social support, anxiety as a personality trait, and avoidant coping style were directly associated with SRQ score. Public health policies should address the need for mental health care among deported migrants. PMID- 25118677 TI - [Hereditary multiple exostoses]. AB - BACKGROUND: Hereditary multiple exostosis (HME) is a hereditary autosomal dominant disease in which multiple exostoses occur. Typically, the exostoses are primarily located at the metaphysis and migrate with continued growth towards the diaphysis. Clinical problems are caused by local pain, impingement of muscle tendons and neurovascular structures, malformation - especially in the forearm - and malignant transformation - especially exostoses at the trunc and pelvic girdle. METHODS: A causal therapy is currently not available. Mechanical irritation is an indication for resection of the exostosis. Axial deviation of the lower extremity is treated according to the same principles as primary malalignments (temporary hemiepiphysiodesis/corrective osteotomy). RESULTS: The indication for correction of axial deviation at the upper extremity depends on age, extent as well as functional and cosmetic impairment. This should be discussed with the patient in detail. The patient has to be informed about the risk of malignant transformation after cessation of growth. Growing mass or new occurrence of symptoms after end of growth are suspicious and require further diagnostic examinations. PMID- 25118676 TI - Two acidic, anticoagulant PLA2 isoenzymes purified from the venom of monocled cobra Naja kaouthia exhibit different potency to inhibit thrombin and factor Xa via phospholipids independent, non-enzymatic mechanism. AB - BACKGROUND: The monocled cobra (Naja kaouthia) is responsible for snakebite fatality in Indian subcontinent and in south-western China. Phospholipase A2 (PLA2; EC 3.1.1.4) is one of the toxic components of snake venom. The present study explores the mechanism and rationale(s) for the differences in anticoagulant potency of two acidic PLA2 isoenzymes, Nk-PLA2alpha (13463.91 Da) and Nk-PLA2beta (13282.38 Da) purified from the venom of N. kaouthia. PRINCIPAL FINDINGS: By LC-MS/MS analysis, these PLA2s showed highest similarity (23.5% sequence coverage) with PLA2 III isolated from monocled cobra venom. The catalytic activity of Nk-PLA2beta exceeds that of Nk-PLA2alpha. Heparin differentially regulated the catalytic and anticoagulant activities of these Nk PLA2 isoenzymes. The anticoagulant potency of Nk-PLA2alpha was comparable to commercial anticoagulants warfarin, and heparin/antithrombin-III albeit Nk PLA2beta demonstrated highest anticoagulant activity. The anticoagulant action of these PLA2s was partially contributed by a small but specific hydrolysis of plasma phospholipids. The strong anticoagulant effect of Nk-PLA2alpha and Nk PLA2beta was achieved via preferential, non-enzymatic inhibition of FXa (Ki = 43 nM) and thrombin (Ki = 8.3 nM), respectively. Kinetics study suggests that the Nk PLA2 isoenzymes inhibit their "pharmacological target(s)" by uncompetitive mechanism without the requirement of phospholipids/Ca(2+). The anticoagulant potency of Nk-PLA2beta which is higher than that of Nk-PLA2alpha is corroborated by its superior catalytic activity, its higher capacity for binding to phosphatidylcholine, and its greater strength of thrombin inhibition. These PLA2 isoenzymes thus have evolved to affect haemostasis by different mechanisms. The Nk-PLA2beta partially inhibited the thrombin-induced aggregation of mammalian platelets suggesting its therapeutic application in the prevention of unwanted clot formation. CONCLUSION/SIGNIFICANCE: In order to develop peptide-based superior anticoagulant therapeutics, future application of Nk-PLA2alpha and Nk PLA2beta for the treatment and/or prevention of cardiovascular disorders are proposed. PMID- 25118679 TI - [Spondylosclerosis hemispherica: a rare radiological syndrome of the spine]. AB - BACKGROUND: Spondylosclerosis hemispherica is a rare syndrome of the spine and was described first by Dihlmann. The typical radiographic appearance is a hemispherical sclerosis of the vertebral body, which is accompanied by pain in the affected region. Usually it appears at the lower lumbar spine. The etiology varies and includes degenerative disk diseases, scoliosis, bacterial infections, ankylosing spondylitis, osteoid osteoma, and malignant diseases.The radiological findings of 2 patients with spondylosclerosis hemispherica are presented and the current literature discussed. MATERIAL AND METHODS: Two women (33 and 60 years old) with spondylosclerosis hemispherica of the lower spine suffered from low back pain and fulfilled all criteria of Dihlmann's description. Malignant disease was excluded in both cases with a broad diagnostic workup (lab values, x-ray, CT scan, MRI) and in one case a biopsy from the affected vertebra was taken. RESULTS: In both cases all radiological findings demonstrated the typical changes of spondylosclerosis hemispherica with sclerosis of the vertebra body and erosions at the upper and inferior end plates. Malignant disease was excluded in one case with a biopsy and in the other case with noninvasive diagnostic procedures. Both patients were treated nonsurgically. During clinical follow-up, the patients were in a good condition with decreasing regional low back pain and no ongoing radiological changes in the affected vertebral bodies. CONCLUSION: Spondylosclerosis hemispherica is a syndrome with a typical radiographic appearance. The etiology of spondylosclerosis hemispherica is manifold; however, malignancy must be excluded. In most cases, noninvasive diagnostics are sufficient to rule out malignant growth even in cases with concomitant degenerative changes of the affected segment. Thus, there is no need for a biopsy except in cases with ambiguous results. Subsequently, close clinical and radiological follow-up of the patients with spondylosclerosis hemispherica is necessary. PMID- 25118678 TI - [Surgical treatment of scapholunate ligament injuries: clinical and radiological results]. AB - BACKGROUND: The purpose of this work was to retrospectively evaluate clinical and radiological results after surgical treatment for scapholunate ligament ruptures. MATERIALS AND METHODS: Measurements of range of motion, strength, and angles, as well as postoperative score assessments were performed in 32 patients. RESULTS: The average mobility in the operated wrist was 52 degrees for flexion, extension 57 degrees , radial 24 degrees , ulnar deviation 31 degrees and forearm rotation outward 88 degrees and inward 89 degrees . The recovery of force was 89% compared with the healthy hand. It showed an average skapholunar angle of 63 degrees , a radioulnar angle of 22 degrees and an average carpal height according to Nattrass of 1.49. Our patients rated the operation result with a median DASH score of 11 points (range 0-70.8 points). The median objective Mayo Wrist Score was 80 points (range 45-100 points). CONCLUSION: Surgical treatment of scapholunate ligament rupture, especially against the background of carpal collapse, is a very satisfactory method with very good results in the objective function and strength, and a high level of patient satisfaction. PMID- 25118680 TI - [Cement-free and cemented Excia hip shaft prosthesis: comparison of intermediate term results]. AB - AIM OF THE STUDY: For fixation of total hip prostheses, cemented and cement-free techniques are available. Normally, anchoring techniques and the definitive endoprosthesis model are determined preoperatively based on the available information, such as the quality of bone. Some newer endoprosthesis models utilize the same instruments for both implantation techniques. In this way it is possible to decide on the final anchoring technique intraoperatively. Because such a combined endoprosthesis system has been used in our clinic for 10 years, we were interested in the clinical results at the intermediate stage. MATERIAL AND METHODS: In a prospective, non-randomized study 105 pairs from a continuing series were formed from 105 cases treated with cement-free prostheses and the latest cemented shaft implants from the same year. In this way a total of 210 hip shaft endoprostheses from the years 2002 to 2006 were included in the study. After an average time period of 6.3 years (range 4.5-8.2 years) the patients were recalled for a follow-up examination. The clinical results, early and late complications were analyzed. The immediately postoperative X-ray images and those from the follow-up examination were evaluated by an independent external expert with respect to primary positioning, migration and any signs of loosening. RESULTS: At the follow-up examination at an average of 6.3 years the quota was 73%. The indications for cement-free/cemented total hip endoprosthesis were: primary arthritis 87%/98%, secondary arthritis 10%/2% and others 3%/0%. At the time of the last follow-up examination 4 and 14 patients, respectively, had died. The visual analog scale (VAS) for pain was given as 0.72/0.78. The Harris hip score improved from 54/48 to 93/90 points. The implant-related survival rate was 99.5%. Due to a periprosthetic fracture one of the cemented shafts had to be removed. Luxation occurred in 3/2 cases, respectively, of which 4 could be conservatively treated. In one cement-free case a head elongation and a change to an inlay with an anti-luxation shoulder was necessary. A fracture of the trochanter major was conservatively treated and an intraoperative shaft fissure was stabilized with wire cerclage and titan banding. The radiological evaluation showed no implant loosening or statistically significant differences in the shaft positioning. DISCUSSION: Short and intermediate clinical and radiological results showed no differences in patients of similar average age in the sixth decade of life. The significant improvements in the Harris hip score and the range of movement could be confirmed in the intermediate term and are comparable to other current implants. It can be concluded that an intraoperative decision on the fixation technique based on the macroscopically visible bone quality supports the reliably good results of both methods. PMID- 25118681 TI - [Partial knee replacement]. PMID- 25118683 TI - Answer to the letter to the editor of L. Uhrenholt et al. concerning "do X-ray occult fractures play a role in chronic pain following a whiplash injury?" by Hertzum-Larsen R, Petersen H, Kasch H, Bendix T, Eur Spine J, 2014; DOI 10.1007/s00586-014-3362-3. PMID- 25118689 TI - Erysipeloid Hodgkin lymphoma. PMID- 25118684 TI - Epithelioid hemangioendothelioma of the spine: results at seven years of average follow-up in a series of 10 cases surgically treated and a review of literature. AB - PURPOSE: To review a series of ten cases with epithelioid hemangioendothelioma of the spine, that have undergone surgery to describe clinical presentation, results and complications associated with surgical treatment; a review of literature reporting the main characteristics of the cases already published has been reported. METHODS: A review of patients affected by epithelioid hemangioendothelioma surgically treated by the senior author from 1995 to 2012 was carried out. Ten cases were identified and clinical and radiological characteristics, therapy, complications and survival were valued. RESULTS: Wide margin was achieved in two out of ten cases, marginal margin in seven and intralesional margin in one case. Average intraoperative blood loss was about 2,800 ml. Reported complications were one case of cord injury, one of dural tear, two cases of massive blood loss, a case of reconstruction failure, a wound dehiscence with deep infection, a pneumonia episode and a deep vein thrombosis with pulmonary embolism. Average follow-up was 84.4 months. Two local recurrences, after 32 and 37 months and two deaths for metastasis, after 14 and 36 months, were reported. Although several chemotherapy protocols are available for the treatment of EH of soft tissue, they are not relevant for the bone. CONCLUSIONS: Wide surgery is probably associated with a better prognosis. Indeed most deaths and local recurrences reported in literature happened after intralesional surgery or chemotherapy/RT alone. The presenting study suggests that the best approach to achieve long-term local control and a major survival could be wide surgery, nevertheless more cases series are necessary to verify survival rate. PMID- 25118685 TI - Comparison between walking test and treadmill test for intermittent claudication associated with lumbar spinal canal stenosis. AB - PURPOSE: To clarify the priorities of the walking test and the treadmill test for intermittent claudication of lumbar canal stenosis. METHODS: The study population comprised 45 subjects, with a mean age of 72.6 years. An investigator walked with the subjects during the walking test or watched the subjects walking on the treadmill machine in the treadmill test. RESULTS: The pain scales became significantly worse after the walking test. Ten patients who were diagnosed as root symptom type or cauda equine symptoms were subsequently diagnosed as mixed type by the walking test. The numbers of patients who experienced muscle weakness that was not revealed at rest were eight with the walking test and seven with the treadmill test. The numbers of patients who experienced sensory disturbance that was not observed at rest were seven with the walking test and two with the treadmill test. CONCLUSIONS: The walking test detected significantly more symptoms that were not detected at rest than the treadmill test. PMID- 25118690 TI - Site-directed mutagenesis of IRX9, IRX9L and IRX14 proteins involved in xylan biosynthesis: glycosyltransferase activity is not required for IRX9 function in Arabidopsis. AB - Xylans constitute the main non-cellulosic polysaccharide in the secondary cell walls of plants. Several genes predicted to encode glycosyltransferases are required for the synthesis of the xylan backbone even though it is a homopolymer consisting entirely of beta-1,4-linked xylose residues. The putative glycosyltransferases IRX9, IRX14, and IRX10 (or the paralogs IRX9L, IRX14L, and IRX10L) are required for xylan backbone synthesis in Arabidopsis. To investigate the function of IRX9, IRX9L, and IRX14, we identified amino acid residues known to be essential for catalytic function in homologous mammalian proteins and generated modified cDNA clones encoding proteins where these residues would be mutated. The mutated gene constructs were used to transform wild-type Arabidopsis plants and the irx9 and irx14 mutants, which are deficient in xylan synthesis. The ability of the mutated proteins to complement the mutants was investigated by measuring growth, determining cell wall composition, and microscopic analysis of stem cross-sections of the transgenic plants. The six different mutated versions of IRX9 and IRX9-L were all able to complement the irx9 mutant phenotype, indicating that residues known to be essential for glycosyltransferases function in homologous proteins are not essential for the biological function of IRX9/IRX9L. Two out of three mutated IRX14 complemented the irx14 mutant, including a mutant in the predicted catalytic amino acid. A IRX14 protein mutated in the substrate-binding DxD motif did not complement the irx14 mutant. Thus, substrate binding is important for IRX14 function but catalytic activity may not be essential for the function of the protein. The data indicate that IRX9/IRX9L have an essential structural function, most likely by interacting with the IRX10/IRX10L proteins, but do not have an essential catalytic function. Most likely IRX14 also has primarily a structural role, but it cannot be excluded that the protein has an important enzymatic activity. PMID- 25118691 TI - An appraisal of female sex work in Nigeria--implications for designing and scaling up HIV prevention programmes. AB - BACKGROUND: The HIV epidemic in Nigeria is complex with diverse factors driving the epidemic. Accordingly, Nigeria's National Agency for the Control of AIDS is coordinating a large-scale initiative to conduct HIV epidemic appraisals across all states. These appraisals will help to better characterize the drivers of the epidemic and ensure that the HIV prevention programmes match the local epidemic context, with resources allocated to interventions that have the greatest impact locally. Currently, the mapping and size estimation of Female Sex Workers (FSWs)- a major component of the appraisal has been completed in seven states. These states are using the data generated to plan, prioritize and scale-up sub-national HIV prevention programmes. METHODOLOGY: It involved a two-level process of identifying and validating locations where FSWs solicit and/or meet clients ("hotspots"). In the first level, secondary key informants were interviewed to collect information about the geographic location and description of the hotspots. For the second level, FSWs were interviewed at each hotspot and information on population size estimates, typologies and operational dynamics of the FSWs were collected. RESULTS: Across the seven states, a total of 17,266 secondary key informants and 5,732 FSWs were interviewed. 10,233 hotspots were identified with an estimated 126,489 FSWs ranging from 5,920 in Anambra to 46,691 in Lagos. The most common hotspots were bars/nightclubs (30%), hotels/lodges (29.6%), streets (16.6%), and brothels (14.6%). Furthermore, the population density of FSWs (per thousand adult men) across the states ranged from 2 in Anambra to 17 in the Federal Capital Territory. CONCLUSION: FSW populations in Nigeria are large and diverse, with substantial differences between and within states. Improved understanding of the location, population size, density, organizational typologies and clients of sex work has informed and is central to Nigeria's planning process for scaling up focused HIV prevention programmes. PMID- 25118692 TI - Pregnancy-related systemic lupus erythematosus: clinical features, outcome and risk factors of disease flares--a case control study. AB - OBJECTIVE: To investigate the clinical features, outcome, and risk factors of disease flares in patients with pregnancy-related lupus (PRL). METHODS: Medical charts of 155 consecutive PRL inpatients were systematically reviewed, including demographic data, clinical features, laboratory findings, treatment, complications, and outcome. RESULTS: PRL cases were divided into active (a-PRL) (n = 82, 53.0%) and stable lupus (s-PRL) (n = 73, 47.0%). Compared with nonpregnant active female systemic lupus erythematosus (SLE) patients, a-PRL including new-onset lupus (n-PRL) and flare lupus (f-PRL) (n = 41 respectively), had a higher incidence of renal and hematological involvement but less mucocutaneous and musculoskeletal involvement (p<0.05). The incidence of preeclampsia/eclampsia, fetal loss, and preterm birth were significantly higher in a-PRL than in s-PRL (p<0.05). Despite receiving a more vigorous glucocorticoid treatment, a-PRL mothers had a poorer prognosis (p<0.001). Five (6.1%) of them died and 13 (15.9%) developed severe irreversible organ failure, whereas none of these events was observed in the s-PRL group. Multivariate logistic analysis indicated that a history of lupus flares and serological activity (hypocomplementemia and/or anti-dsDNA positivity) at the time of conception were associated with lupus flares in PRL mothers. CONCLUSIONS: SLE patients with a flare history and serological activity at the time of conception were at an increased risk of disease flares during pregnancy and puerperium. a-PRL patients were more prone to renal and hematological involvement, pregnancy complications, and a poorer prognosis despite more vigorous glucocorticoid treatment. PMID- 25118694 TI - Statin therapy is associated with improved survival in patients with non-serous papillary epithelial ovarian cancer: a retrospective cohort analysis. AB - AIM: To determine whether statin use is associated with improved epithelial ovarian cancer (OvCa) survival. METHODS: This is a single-institution retrospective cohort review of patients treated for OvCa between 1992 and 2013. Inclusion criteria were International Federation of Gynecology and Obstetrics (FIGO) stage I-IV OvCa. The primary exposures analyzed were hyperlipidemia and statin use. The primary outcomes were progression-free survival (PFS) and disease specific survival (DSS). RESULTS: 442 patients met inclusion criteria. The cohort was divided into three groups: patients with hyperlipidemia who used statins (n = 68), patients with hyperlipidemia who did not use statins (n = 28), and patients without hyperlipidemia (n = 346). OvCa outcomes were evaluated. When we analyzed the entire cohort, we found no significant differences in PFS or DSS among the groups. The median PFS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 21.7, 13.6, and 14.7 months, respectively (p = 0.69). Median DSS for hyperlipidemics using statins, hyperlipidemics not using statins, and non-hyperlipidemics was 44.2, 75.7, and 41.5 months, respectively (p = 0.43). These findings did not change after controlling for confounders. However, a secondary analysis revealed that, among patients with non-serous-papillary subtypes of OvCa, statin use was associated with a decrease in hazards of both disease recurrence (adjusted HR = 0.23, p = 0.02) and disease-specific death (adjusted HR = 0.23, p = 0.04). To augment the findings in the retrospective cohort, the histology-specific effects of statins were also evaluated in vitro using proliferation assays. Here, statin treatment of cell lines resulted in a variable level of cytotoxicity. CONCLUSION: Statin use among patients with non-serous-papillary OvCa was associated with improvement in both PFS and DSS. PMID- 25118695 TI - Involvement of the carboxyl-terminal region of the yeast peroxisomal half ABC transporter Pxa2p in its interaction with Pxa1p and in transporter function. AB - BACKGROUND: The peroxisome is a single membrane-bound organelle in eukaryotic cells involved in lipid metabolism, including beta-oxidation of fatty acids. The human genetic disorder X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene (encoding ALDP, a peroxisomal half ATP-binding cassette [ABC] transporter). This disease is characterized by defective peroxisomal beta-oxidation and a large accumulation of very long-chain fatty acids in brain white matter, adrenal cortex, and testis. ALDP forms a homodimer proposed to be the functional transporter, whereas the peroxisomal transporter in yeast is a heterodimer comprising two half ABC transporters, Pxa1p and Pxa2p, both orthologs of human ALDP. While the carboxyl-terminal domain of ALDP is engaged in dimerization, it remains unknown whether the same region is involved in the interaction between Pxa1p and Pxa2p. METHODS/PRINCIPAL FINDINGS: Using a yeast two-hybrid assay, we found that the carboxyl-terminal region (CT) of Pxa2p, but not of Pxa1p, is required for their interaction. Further analysis indicated that the central part of the CT (designated CT2) of Pxa2p was indispensable for its interaction with the carboxyl terminally truncated Pxa1_NBD. An interaction between the CT of Pxa2p and Pxa1_NBD was not detected, but could be identified in the presence of Pxa2_NBD-CT1. A single mutation of two conserved residues (aligned with X-ALD-associated mutations at the same positions in ALDP) in the CT2 of the Pxa2_NBD-CT protein impaired its interaction with Pxa1_NBD or Pxa1_NBD CT, resulting in a mutant protein that exhibited a proteinase K digestion profile different from that of the wild-type protein. Functional analysis of these mutant proteins on oleate plates indicated that they were defective in transporter function. CONCLUSIONS/SIGNIFICANCE: The CT of Pxa2p is involved in its interaction with Pxa1p and in transporter function. This concept may be applied to human ALDP studies, helping to establish the pathological mechanism for CT related X-ALD disease. PMID- 25118696 TI - Analysis of the Citrullus colocynthis transcriptome during water deficit stress. AB - Citrullus colocynthis is a very drought tolerant species, closely related to watermelon (C. lanatus var. lanatus), an economically important cucurbit crop. Drought is a threat to plant growth and development, and the discovery of drought inducible genes with various functions is of great importance. We used high throughput mRNA Illumina sequencing technology and bioinformatic strategies to analyze the C. colocynthis leaf transcriptome under drought treatment. Leaf samples at four different time points (0, 24, 36, or 48 hours of withholding water) were used for RNA extraction and Illumina sequencing. qRT-PCR of several drought responsive genes was performed to confirm the accuracy of RNA sequencing. Leaf transcriptome analysis provided the first glimpse of the drought responsive transcriptome of this unique cucurbit species. A total of 5038 full-length cDNAs were detected, with 2545 genes showing significant changes during drought stress. Principle component analysis indicated that drought was the major contributing factor regulating transcriptome changes. Up regulation of many transcription factors, stress signaling factors, detoxification genes, and genes involved in phytohormone signaling and citrulline metabolism occurred under the water deficit conditions. The C. colocynthis transcriptome data highlight the activation of a large set of drought related genes in this species, thus providing a valuable resource for future functional analysis of candidate genes in defense of drought stress. PMID- 25118697 TI - The effect of lentivirus-mediated PSPN genetic engineering bone marrow mesenchymal stem cells on Parkinson's disease rat model. AB - Persephin (PSPN) is one of the neurotrophic factors of the glial cell line derived neurotrophic factor (GDNF) family ligands (GFLs) which have been found to promote the survival of specific populations of neurons. The aim of this study was to assess the potential therapeutic function of gene-modified mesenchymal stem cells (MSCs)-Lv-PSPN-MSCs in 6-OHDA-induced Parkinson's disease (PD) rats models. Here, we worked on the isolation, purification, identification and amplification of MSCs in vitro. The expression analysis revealed that several of the neural marker proteins like nestin, GFAP and S100 were expressed by rat MSCs. MES23.5 cells co-cultured with Lv-PSPN-MSCs showed less 6-OHDA induced cell death than control cells in vitro. When Lv-PSPN-MSCs were injected into the striatum of PD rats, we observed the survival rate, migration, differentiation and the behavior change of PD rats. We found that Lv-PSPN-MSCs showed higher survival rate in rat brain compared with Lv-null-MSCs. Rotational behavior showed that rats receiving Lv-PSPN-MSCs showed the most significant improvement compared with those in other groups. HPLC results showed the content of DA in striatum of rats which received Lv-PSPN-MSCs was highest compared with those in other groups. In conclusion, our results suggest that transplantation of Lv-PSPN-MSCs can lead to remarkable therapeutic effects in PD rats. PMID- 25118699 TI - Atopic Dermatitis Burden Scale for Adults: Development and Validation of a New Assessment Tool. AB - Atopic dermatitis (AD) occurs in approximately 2-3% of adults. The aim of this study was to develop and validate the self-administered Atopic Dermatitis Burden Scale for Adults (ABS-A). Patients were enrolled consecutively from those attending the Station Thermale Avene for a diagnosis of AD. ABS-A was developed using standard methodology, and consisted of 3 phases: exploratory, development, and validation. Internal consistency (Cronbach's alpha), concurrent validity (Spearman's correlation between ABS-A, SF-12 and Dermatology Life Quality Index [DLQI)]), and discriminant validity, were analysed. A total of 128 adults (68.8% females) completed the ABS-A, consisting of 18 items grouped into 4 domains. ABS A showed good internal coherence (Cronbach's alpha, 0.89) and was correlated with both SF-12 components [r = -0.36, p < 0.0001 (Physical); r = -0.52, p < 0.0001 (Mental)] and DLQI (r = 0.78; p < 0.0001). The ABS-A score varied significantly according to AD severity. To our knowledge, ABS-A is the first specific tool for assessing AD burden in adult patients. PMID- 25118698 TI - Rapid detection of Mycobacterium tuberculosis by recombinase polymerase amplification. AB - Improved access to effective tests for diagnosing tuberculosis (TB) has been designated a public health priority by the World Health Organisation. In high burden TB countries nucleic acid based TB tests have been restricted to centralised laboratories and specialised research settings. Requirements such as a constant electrical supply, air conditioning and skilled, computer literate operators prevent implementation of such tests in many settings. Isothermal DNA amplification technologies permit the use of simpler, less energy intensive detection platforms more suited to low resource settings that allow the accurate diagnosis of a disease within a short timeframe. Recombinase Polymerase Amplification (RPA) is a rapid, low temperature isothermal DNA amplification reaction. We report here RPA-based detection of Mycobacterium tuberculosis complex (MTC) DNA in <20 minutes at 39 degrees C. Assays for two MTC specific targets were investigated, IS6110 and IS1081. When testing purified MTC genomic DNA, limits of detection of 6.25 fg (IS6110) and 20 fg (IS1081)were consistently achieved. When testing a convenience sample of pulmonary specimens from suspected TB patients, RPA demonstrated superior accuracy to indirect fluorescence microscopy. Compared to culture, sensitivities for the IS1081 RPA and microscopy were 91.4% (95%CI: 85, 97.9) and 86.1% (95%CI: 78.1, 94.1) respectively (n = 71). Specificities were 100% and 88.6% (95% CI: 80.8, 96.1) respectively. For the IS6110 RPA and microscopy sensitivities of 87.5% (95%CI: 81.7, 93.2) and 70.8% (95%CI: 62.9, 78.7) were obtained (n = 90). Specificities were 95.4 (95% CI: 92.3,98.1) and 88% (95% CI: 83.6, 92.4) respectively. The superior specificity of RPA for detecting tuberculosis was due to the reduced ability of fluorescence microscopy to distinguish Mtb complex from other acid fast bacteria. The rapid nature of the RPA assay and its low energy requirement compared to other amplification technologies suggest RPA-based TB assays could be of use for integration into a point-of-care test for use in resource constrained settings. PMID- 25118700 TI - Modulation of short-latency afferent inhibition depends on digit and task relevance. AB - Short-latency afferent inhibition (SAI) occurs when a single transcranial magnetic stimulation (TMS) pulse delivered over the primary motor cortex is preceded by peripheral electrical nerve stimulation at a short inter-stimulus interval (~ 20-28 ms). SAI has been extensively examined at rest, but few studies have examined how this circuit functions in the context of performing a motor task and if this circuit may contribute to surround inhibition. The present study investigated SAI in a muscle involved versus uninvolved in a motor task and specifically during three pre-movement phases; two movement preparation phases between a "warning" and "go" cue and one movement initiation phase between a "go" cue and EMG onset. SAI was tested in the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles in twelve individuals. In a second experiment, the origin of SAI modulation was investigated by measuring H-reflex amplitudes from FDI and ADM during the motor task. The data indicate that changes in SAI occurred predominantly in the movement initiation phase during which SAI modulation depended on the specific digit involved. Specifically, the greatest reduction in SAI occurred when FDI was involved in the task. In contrast, these effects were not present in ADM. Changes in SAI were primarily mediated via supraspinal mechanisms during movement preparation, while both supraspinal and spinal mechanisms contributed to SAI reduction during movement initiation. PMID- 25118702 TI - Optimizing the discovery and clinical translation of nanoparticles: could microfluidics hold the key? PMID- 25118703 TI - Recent progress in multidrug delivery to cancer cells by liposomes. PMID- 25118704 TI - Formulating the magic bullet: barriers to clinical translation of nanoparticle cancer gene therapy. PMID- 25118701 TI - Impact of early life adversity on reward processing in young adults: EEG-fMRI results from a prospective study over 25 years. AB - Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway. PMID- 25118707 TI - A preliminary study on the quality and safety of milk in donkeys positive for Toxoplasma gondii. AB - Toxoplasmosis is one of the five parasitic diseases considered as a priority for public health action. The consumption of raw milk products represents a possible risk, in particular for certain categories of people. The aim of this study was to evaluate the possible effects of Toxoplasma gondii on milk yield and quality in sero-positive animals with parasitemia. Eighteen healthy lactating Amiata jennies, between 90 and 180 days were included in the study. Four donkeys scored positive for immunofluorescent antibody test (IFAT), and each IFAT positive donkey presented parasitic DNA both in the blood and milk. No significant differences were found between milk yield in PCR-positive donkeys compared with the negative cases, however the former tended to have a greater production. Milk quality in the positive donkeys showed a significantly lower percentage of casein (0.72% v. 0.81%) and ash (0.32% v. 0.37%). Positive cases had a highly significant larger average diameter of globules (2.35 um) and fewer globules/ml (2.39 * 10(8)). Somatic cell and bacterial counts were normal and in agreement with the literature. Toxoplasma gondii did not seem to present clinical forms in lactating jennies. Further in vivo studies are needed to further assess the risk of T. gondii transmission through donkey milk, together with the impact of different stages of infection on milk quality. PMID- 25118708 TI - Association of a polymorphism in the BIRC6 gene with pseudoexfoliative glaucoma. AB - Recently an association was observed between alleles in genes of the unfolded protein response pathway and primary open angle glaucoma (POAG). The goal of the current study is to investigate the role of these two genes, protein disulphide isomerase A member 5 (PDIA5) and baculoviral IAP repeat containing 6 (BIRC6), in different forms of glaucoma. 278 patients with POAG, 132 patients with primary angle closure glaucoma (PACG) and 135 patients with pseudoexfoliative glaucoma (PEXG) were genotyped for single nucleotide polymorphisms (SNPs) rs11720822 in PDIA5 and 471 POAG, 184 PACG and 218 PEXG patients were genotyped for rs2754511 in BIRC6. Genotyping was done by allelic discrimination PCR, and genotype and allele frequencies were calculated. Logistic regression analyses were performed using R software to determine the association of these SNPs with glaucoma. The allele and genotype frequencies of rs11720822 in PDIA5 were not associated with POAG, PACG or PEXG. The TT genotype of rs2754511 in BIRC6 was found to be protective for PEXG (p = 0.05, OR 0.42 [0.22-0.81]) in the Pakistani population, but not for POAG or PACG. This study did not confirm a previously reported association of risk alleles in PDIA5 and BIRC6 with POAG, but did demonstrate a protective role of the T allele of rs2754511 in the BIRC6 gene in PEXG. This supports a role for the unfolded protein response pathway and regulation of apoptotic cell death in the pathogenesis of PEXG. PMID- 25118710 TI - Fullerene C60 functionalized gamma-Fe2O3 magnetic nanoparticle: Synthesis, characterization, and biomedical applications. AB - Hybrid magnetic nanoparticles composed from C60 fullerene and gamma-Fe2O3 were synthesized by hydrothermal method. XRD, FT-IR, VSM, SEM, and HR-TEM were employed for characterizations. The magnetic saturation value of C60-gamma-Fe2O3 magnetic nanoparticles was 66.5 emu g(-1). Concentration of Fe in nanoparticles as determined by ICP-OES was 40.7% Fe. Particle size of C60-gamma-Fe2O3 magnetic nanoparticles was smaller than 10 nm. Maximum adsorption capacity of C60-gamma Fe2O3 for flurbiprofen, a non-steroidal anti-inflammatory drug, was calculated from Langmuir isotherm as 142.9 mg g(-1). PMID- 25118711 TI - Multimode laser cooling and ultra-high sensitivity force sensing with nanowires. AB - Photo-induced forces can be used to manipulate and cool the mechanical motion of oscillators. When the oscillator is used as a force sensor, such as in atomic force microscopy, active feedback is an enticing route to enhance measurement performance. Here we show broadband multimode cooling of -23 dB down to a temperature of 8 +/- 1 K in the stationary regime. Through the use of periodic quiescence feedback cooling, we show improved signal-to-noise ratios for the measurement of transient signals. We compare the performance of real feedback to numerical post processing of data and show that both methods produce similar improvements to the signal-to-noise ratio of force measurements. We achieved a room temperature force measurement sensitivity of <2 * 10(-16)N with integration time of less than 0.1 ms. The high precision and fast force microscopy results presented will potentially benefit applications in biosensing, molecular metrology, subsurface imaging and accelerometry. PMID- 25118709 TI - Structural characterization of a Gcn5-related N-acetyltransferase from Staphylococcus aureus. AB - The Gcn5-related N-acetyltransferases (GNATs) are ubiquitously expressed in nature and perform a diverse range of cellular functions through the acetylation of small molecules and protein substrates. Using activated acetyl coenzyme A as a common acetyl donor, GNATs catalyse the transfer of an acetyl group to acceptor molecules including aminoglycoside antibiotics, glucosamine-6-phosphate, histones, serotonin and spermidine. There is often only very limited sequence conservation between members of the GNAT superfamily, in part, reflecting their capacity to bind a diverse array of substrates. In contrast, the secondary and tertiary structures are highly conserved, but then at the quaternary level there is further diversity, with GNATs shown to exist in monomeric, dimeric, or tetrameric states. Here we describe the X-ray crystallographic structure of a GNAT enzyme from Staphylococcus aureus with only low sequence identity to previously solved GNAT proteins. It contains many of the classical GNAT motifs, but lacks other hallmarks of the GNAT fold including the classic beta-bulge splayed at the beta-sheet interface. The protein is likely to be a dimer in solution based on analysis of the asymmetric unit within the crystal structure, homology with related GNAT family members, and size exclusion chromatography. The study provides the first high resolution structure of this enzyme, providing a strong platform for substrate and cofactor modelling, and structural/functional comparisons within this diverse enzyme superfamily. PMID- 25118713 TI - Conducting research and collaborating with researchers: the experience of clinicians in a residential treatment center. AB - This paper describes the experience of clinicians in conducting research and collaborating with academic researchers. As part of clinical routine of a residential program for adolescent substance abusers, empirical data have been collected to assess client's needs before and after treatment, improve clinical practice, and identify barriers to change. Some of the challenges faced and the benefits learned in conducting these studies are presented. In addition to highlighting the convergence of research interests between clinicians and academicians, the conclusion offers general recommendations to foster these partnerships and solidify the scientific-practitioner model. PMID- 25118712 TI - Systematics of spiny predatory katydids (Tettigoniidae: Listroscelidinae) from the Brazilian Atlantic Forest based on morphology and molecular data. AB - Listroscelidinae (Orthoptera: Tettigoniidae) are insectivorous Pantropical katydids whose taxonomy presents a long history of controversy, with several genera incertae sedis. This work focused on species occurring in the Brazilian Atlantic Forest, one of the world's most threatened biomes. We examined material deposited in scientific collections and visited 15 conservation units from Rio de Janeiro to southern Bahia between November 2011 and January 2012, catching 104 specimens from 10 conservation units. Based on morphological and molecular data we redefined Listroscelidini, adding a new tribe, new genus and eight new species to the subfamily. Using morphological analysis, we redescribed and added new geographic records for six species, synonymized two species and built a provisional identification key for the Atlantic Forest Listroscelidinae. Molecular results suggest two new species and a new genus to be described, possibly by the fission of the genus Hamayulus. We also proposed a 500 bp region in the final portion of the COI to be used as a molecular barcode. Our data suggest that the Atlantic Forest Listroscelidinae are seriously endangered, because they occur in highly preserved forest remnants, show high rates of endemism and have a narrow geographic distribution. Based on our results, we suggest future collection efforts must take into account the molecular barcode data to accelerate species recognition. PMID- 25118714 TI - Drinking pattern, abstention and problem drinking as risk factors for depressive symptoms: evidence from three urban Eastern European populations. AB - PURPOSE: To examine whether the frequency and amount of alcohol consumed in binge drinking sessions, total annual volume of alcohol consumed, problem drinking and abstaining from alcohol are associated with depressive symptoms in Eastern Europe. SUBJECTS AND METHODS: Cross-sectional data from a total of 24,381 participants from general population samples of the Czech Republic (N = 7,601), Russia (N = 6,908) and Poland (N = 9,872) aged 45-69 years in 2002-2005. Depressive symptoms were defined as >= 16 points on the Centre for Epidemiological Studies - Depression (CES-D) scale. Several alcohol related measures were derived using responses from the graduated frequency questionnaire. Binge drinking was defined at several sex-specific thresholds (ranging from 60+ to 140+ g of ethanol) and two frequencies (at least monthly or weekly). Total annual alcohol intake in grams was also extracted. Problem drinking was defined as >= 2 positive answers on the CAGE questionnaire. RESULTS: Problem drinking was consistently associated with approximately a 2-fold increase in odds of depressive symptoms across all countries and in both sexes. Abstaining from alcohol was typically associated with increased odds of depressive symptoms. Analyses separating lifelong abstainers and former drinkers in the Russian cohort revealed that this increased odds was driven by former drinkers. Amongst men, heavy frequent binge drinking was associated with increased odds of depressive symptoms in the Czech Republic and Poland. In women, heavy infrequent binge drinking was associated with increased odds of depressive symptoms in Russia and Poland. Only in Polish men was higher annual volume of alcohol intake associated with increased odds of depressive symptoms. CONCLUSION: Abstaining from alcohol and problem drinking were associated with increased odds of depressive symptoms in these Eastern European populations. Annual volume of alcohol intake as well as frequency and amount of alcohol consumed in a binge drinking session were less consistently associated with depressive symptoms. PMID- 25118715 TI - De novo comparative transcriptome analysis of Acremonium chrysogenum: high-yield and wild-type strains of cephalosporin C producer. AB - beta-lactam antibiotics are widely used in clinic. Filamentous fungus Acremonium chrysogenum is an important industrial fungus for the production of CPC, one of the major precursors of beta-lactam antibiotics. Although its fermentation yield has been bred significantly over the past decades, little is known regarding molecular changes between the industrial strain and the wild type strain. This limits the possibility to improve CPC production further by molecular breeding. Comparative transcriptome is a powerful tool to understand the molecular mechanisms of CPC industrial high yield producer compared to wild type. A total of 57 million clean sequencing reads with an average length of 100 bp were generated from Illumina sequencing platform. 22,878 sequences were assembled. Among the assembled unigenes, 9502 were annotated and 1989 annotated sequences were assigned to 121 pathways by searching against the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Furthermore, we compared the transcriptome differences between a high-yield and a wild-type strain during fermentation. A total of 4329 unigenes with significantly different transcription level were identified, among which 1737 were up-regulated and 2592 were down regulated. 24 pathways were subsequently determined which involve glycerolipid metabolism, galactose metabolism, and pyrimidine metabolism. We also examined the transcription levels of 18 identified genes, including 11 up-regulated genes and 7 down-regulated genes using reverse transcription quantitative -PCR (RT-qPCR). The results of RT-qPCR were consistent with the Illumina sequencing. In this study, the Illumina sequencing provides the most comprehensive sequences for gene expression profile of Acremonium chrysogenum and allows de novo transcriptome assembly while lacking genome information. Comparative analysis of RNA-seq data reveals the complexity of the transcriptome in the fermentation of different yield strains. This is an important public information platform which could be used to accelerate the research to improve CPC production in Acremonium chrysogenum. PMID- 25118716 TI - Skills training of health workers in the use of a non surgical device (PrePex) for adult Safe Male Circumcision. AB - BACKGROUND: Safe Male Circumcision (SMC) is a proven approach for partial protection of men from acquisition of HIV infection. Several sub-Saharan African countries have a target to circumcise 80% of males aged 15 to 49. The use of devices such as PrePex would aid scaling up of SMC. Since most health workers would have no prior experience with use of devices, skills training is needed. This paper explores a skills transfer model at an urban site in Uganda. OBJECTIVE: To assess the practicability and feasibility of rapid short duration training for safe PrePex device use. METHODS: A prospective study, conducted over 8 weeks (August-October 2012) at International Hospital Kampala, an urban Kampala hospital, examining the performance of various health worker cadres after training in the use of a non-surgical device (PrePex). The prospective study obtained approval from the Makerere School of Medicine Research and Ethics Committee and the Uganda National Council of Science and Technology. If eligible, and after the subject signed the informed consent form, they were enrolled into the study. RESULTS: Ten health workers were successfully trained in use of PrePex during a 3 day non-residential on-the-job training course. After the first three days of training, the trained health workers performed 561 placements and 529 device removals successfully. Over all adverse events (AE) rates were below <= 2%; however, there were some differences in AE rates across the cadres trained but not significant (p>0.25 for moderate AEs). CONCLUSION: Rapid training for safe use of the PrePex device is feasible for the range of health workers available for SMC in resource limited settings, but among those with past SMC experience. PMID- 25118720 TI - A comparison of mid-forehead and axillary temperatures in newborn intensive care. AB - OBJECTIVE: To evaluate accuracy of mid-forehead (MFH) thermometry compared with digital axilla (DAT) temperatures in infants in newborn intensive care. STUDY DESIGN: A comparative study of MFH and DAT temperatures of newborn infants receiving tertiary-level intensive care. All admissions were considered and the following exclusion criteria applied: 'in extremis', hypoxic ischemic encephalopathy or non-English-speaking parents. Foot temperatures, infant and environmental variables were measured. RESULT: In all, 783 readings were obtained in 100 infants with a birth weight range 515 to 4885 g (mean 2152 g). The between person correlation was 0.30 (P < 0.001) and the within-person correlation was 0.52 (P < 0.001). Bland-Altman plots showed wide 95% confidence intervals in the differences between MFH and DAT measurements (-0.87 to 1.16 degrees C). Differences were affected by infant variables measured. MFH more accurately predicted DAT measurements in smaller neonates and were less accurate in neonates requiring Bubble Continuous Positive Airway Pressure (CPAP). CONCLUSION: MFH thermometry is not able to replace DAT temperature recording in the newborn intensive care. PMID- 25118717 TI - Regulation of microRNA function in somatic stem cell proliferation and differentiation. AB - microRNAs (miRNAs) are important modulators of development. Owing to their ability to simultaneously silence hundreds of target genes, they have key roles in large-scale transcriptomic changes that occur during cell fate transitions. In somatic stem and progenitor cells--such as those involved in myogenesis, haematopoiesis, skin and neural development--miRNA function is carefully regulated to promote and stabilize cell fate choice. miRNAs are integrated within networks that form both positive and negative feedback loops. Their function is regulated at multiple levels, including transcription, biogenesis, stability, availability and/or number of target sites, as well as their cooperation with other miRNAs and RNA-binding proteins. Together, these regulatory mechanisms result in a refined molecular response that enables proper cellular differentiation and function. PMID- 25118722 TI - Decreasing abundance, increasing diversity and changing structure of the wild bee community (Hymenoptera: Anthophila) along an urbanization gradient. AB - BACKGROUND: Wild bees are important pollinators that have declined in diversity and abundance during the last decades. Habitat destruction and fragmentation associated with urbanization are reported as part of the main causes of this decline. Urbanization involves dramatic changes of the landscape, increasing the proportion of impervious surface while decreasing that of green areas. Few studies have investigated the effects of urbanization on bee communities. We assessed changes in the abundance, species richness, and composition of wild bee community along an urbanization gradient. METHODOLOGY/PRINCIPAL FINDINGS: Over two years and on a monthly basis, bees were sampled with colored pan traps and insect nets at 24 sites located along an urbanization gradient. Landscape structure within three different radii was measured at each study site. We captured 291 wild bee species. The abundance of wild bees was negatively correlated with the proportion of impervious surface, while species richness reached a maximum at an intermediate (50%) proportion of impervious surface. The structure of the community changed along the urbanization gradient with more parasitic species in sites with an intermediate proportion of impervious surface. There were also greater numbers of cavity-nesting species and long-tongued species in sites with intermediate or higher proportion of impervious surface. However, urbanization had no effect on the occurrence of species depending on their social behavior or body size. CONCLUSIONS/SIGNIFICANCE: We found nearly a third of the wild bee fauna known from France in our study sites. Indeed, urban areas supported a diverse bee community, but sites with an intermediate level of urbanization were the most speciose ones, including greater proportion of parasitic species. The presence of a diverse array of bee species even in the most urbanized area makes these pollinators worthy of being a flagship group to raise the awareness of urban citizens about biodiversity. PMID- 25118724 TI - Cervical cancer biopsy reporting: a review. AB - The terminology for reporting human papillomavirus-associated squamous lesions in the cervix, both in tissue samples and cytology specimens, has suffered from many changes throughout the last years creating confusion in interpreting cervical biopsy and cytology reports by clinicians. This review presents a summary and discussion of the current terminology for reporting results of cervical biopsies and cytology with emphasis in the lower anogenital squamous terminology consensus recommendations for tissue specimens and the 2001 Bethesda Workshop for reporting cytology results. Microscopic features of cervical lesions in tissue samples and cytology specimens are presented. Biomarkers, including p16 and Ki-67, are discussed and how they can help the pathologist when dealing with difficult cases. PMID- 25118725 TI - Calretinin immunohistochemistry versus improvised rapid Acetylcholinesterase histochemistry in the evaluation of colorectal biopsies for Hirschsprung disease. AB - BACKGROUND: Acetylcholinesterase (AChE) histochemistry on rectal mucosal biopsies accurately diagnoses Hirschsprung disease (HD), but is not widely employed as it requires special tissue handling and pathologist expertise. Calretinin immunohistochemistry (IHC) has been reported to be comparable to AChE staining with the loss of expression correlating with aganglionosis. AIM: The aim was to evaluate calretinin IHC as a primary diagnostic tool in comparison to the improvised rapid AChE technique in the diagnosis of HD. MATERIALS AND METHODS: A total of 74 rectal biopsies (18 fresh frozen - 18 cases, 56 formalin fixed - 33 cases) from 51 cases of suspect HD were evaluated with hematoxylin and eosin/AChE/Calretinin. Ten biopsies each from ganglionated and aganglionated segments served as positive and negative controls. Ileal (3), appendiceal (3) and ring bowel (2) biopsies were also included. Two pathologists blinded to the clinical details evaluated the histomorphology with AChE and calretinin. Observations were statistically analyzed and Cohen's k coefficient employed to assess agreement between two pathologists and calretinin and the AChE. RESULTS: The study confirmed HD in 26 and non-HD in 25 cases. There were 7 neonates, 5 low level biopsies and 14 "inadequate" biopsies. The results of calretinin were comparable with AChE with a statistically significant measure of agreement of k = 0.973 between the two. One false-positive case of HD was noted with calretinin. The advantages and disadvantages of calretinin versus AChE are discussed. CONCLUSION: Calretinin is a reliable single immune marker for ruling out HD by its specific positive mucosal staining of formalin fixed rectal biopsy. The improvised AChE staining remains indispensable to confirm HD on fresh biopsies and thus, along with calretinin IHC maximizes the diagnostic accuracy of HD in difficult cases. PMID- 25118726 TI - Evaluation of central nervous system metastases with immunohistochemistry correlation. AB - CONTEXT: Brain metastases are the most common intracranial neoplasms. They are often the first symptom of systemic malignancy. Hence, immunohistochemistry (IHC) is of importance in evaluating the origin of brain metastases. AIMS: The aim was to detect the primary site of brain metastases and evaluate the role of IHC in diagnosing the same. MATERIALS AND METHODS: Data of 74 patients of brain metastases with unknown primary was analyzed. IHC was performed in these cases. The histopathological findings were correlated with clinical and radiological data. RESULTS: Of 74 cases in which IHC was done; the most common primary site was lung (51 cases). Even after applying IHC, the primary could not be diagnosed in 10 cases. CONCLUSION: Brain metastases are often the first indicator of systemic malignancy. Lung is the most common primary site in cases with unknown primary, as deduced by IHC findings. PMID- 25118727 TI - A histopathological study of liver and biliary remnants in the long-term survivors (>10 years) of cases of biliary atresia. AB - CONTEXT: Biliary atresia (BA) is a destructive process affecting both extra- and intra-hepatic bile ducts leading to fibrosis and obliteration of the biliary tree and cirrhosis usually within 2 years. Factors influencing the outcome of portoenterostomy (PE) have not been clearly defined. AIMS: Our aim was to identify children with no evidence of liver disease 10 years or more after PE and to compare the pathology of liver and biliary remnants in this group with those associated with poor outcome. SETTINGS AND DESIGN: Prospective observational study. MATERIALS AND METHODS: Wedge biopsies of liver and portal remnants, taken at the time of PE, where available, were reviewed. The parameters studied were - presence of large bile ducts (>150 MU), degree of fibrosis and bile duct proliferation (BDP), presence of ductal plate malformation (DPM) and age at operation. STATISTICAL ANALYSIS USED: Fisher's exact test with Freeman Halton extension for univariate analysis and Logistic regression analysis as multivariate analysis. RESULTS: Of 68 cases operated between 1995 and 2001, 14 patients survived >10 years and 54 were associated with poor outcome. Large ducts were significantly more in survivors (70% vs. 26%, P = 0.02). DPM was not seen in any of the survivors and was present in 24% of poor outcome group. Fibrosis and BDP were also significantly less among the survivors (P < 0.001, P = 0.03, respectively). The mean ages at operation in the two groups were 66.8 and 89.6 days, respectively. CONCLUSION: From this study, we feel that lower degree of fibrosis and BDP, absence of DPM, presence of large ducts and younger age at operation were associated with better long-term outcome. Of these, degree of fibrosis was the most significant factor. PMID- 25118718 TI - Bidirectional cargo transport: moving beyond tug of war. AB - Vesicles, organelles and other intracellular cargo are transported by kinesin and dynein motors, which move in opposite directions along microtubules. This bidirectional cargo movement is frequently described as a 'tug of war' between oppositely directed molecular motors attached to the same cargo. However, although many experimental and modelling studies support the tug-of-war paradigm, numerous knockout and inhibition studies in various systems have found that inhibiting one motor leads to diminished motility in both directions, which is a 'paradox of co-dependence' that challenges the paradigm. In an effort to resolve this paradox, three classes of bidirectional transport models--microtubule tethering, mechanical activation and steric disinhibition--are proposed, and a general mathematical modelling framework for bidirectional cargo transport is put forward to guide future experiments. PMID- 25118728 TI - A clinicopathological study of interface dermatitis. AB - BACKGROUND: Interface dermatitis (ID) refers to a pattern of skin reaction characterized by an inflammatory infiltrate that appears to obscure the dermo epidermal junction when observed at low power examination and referred to as lichenoid tissue reaction. A wide range of inflammatory skin diseases exhibits interface change with considerable overlap of histological features. The aim of the present study was to study the clinical features and microscopic features of ID. MATERIALS AND METHODS: The material for the present study consisted of skin biopsy samples collected from patients attending the outpatient Department of Dermatology. The study was conducted for a period of 3 years from 2007 to 2010. During this period, a total of 125 cases was studied. RESULTS: In the present study, a total of 125 cases of ID was studied which presented clinically as papulosquamous disorders. Majority of the cases of ID were seen in women (57.6%). Majority of ID were lichen planus (LP) and its variants (63.2%). Clinicopathological concordance was seen in 109 cases (87.2%) and discordance in 16 cases (12.8%). CONCLUSION: The mere presence of an interface lichenoid inflammatory reaction should not be the sole criterion for the diagnosis of LP or one of its many variants, as now seems to be the case. A clinicopathologic correlation is absolutely essential for a conclusive diagnosis of ID. PMID- 25118721 TI - Catecholamine-resistant hypotension and myocardial performance following patent ductus arteriosus ligation. AB - OBJECTIVE: We performed a multicenter study of preterm infants, who were about to undergo patent ductus arteriosus ligation, to determine whether echocardiographic indices of impaired myocardial performance were associated with subsequent development of catecholamine-resistant hypotension following ligation. STUDY DESIGN: A standardized treatment approach for hypotension was followed at each center. Infants were considered to have catecholamine-resistant hypotension if their dopamine infusion was > 15 MUg kg(-1)min(-1). Echocardiograms and cortisol measurements were obtained between 6 and 14 h after the ligation (prior to the presence of catecholamine-resistant hypotension). RESULT: Forty-five infants were enrolled, 10 received catecholamines (6 were catecholamine-responsive and 4 developed catecholamine-resistant hypotension). Catecholamine-resistant hypotension was not associated with decreased preload, shortening fraction or ventricular output. Infants with catecholamine-resistant hypotension had significantly lower levels of systemic vascular resistance and postoperative cortisol concentration. CONCLUSION: We speculate that low cortisol levels and impaired vascular tone may have a more important role than impaired cardiac performance in post-ligation catecholamine-resistant hypotension. PMID- 25118729 TI - Revisiting epidermal growth factor receptor in glioblastoma multiforme: does it play a role in response to therapy? AB - BACKGROUND AND AIM: Glioblastoma multiforme (GBM) are the most aggressive class of cancer of central nervous system with hallmark characteristics that include rampant proliferation, necrosis, and endothelial proliferation. Epidermal growth factor receptor (EGFR) has been implicated as the primary contributor to glioblastoma initiation and succession. The present study was designed to evaluate EGFR protein expression in GBM as predictor of response to therapy and survival. MATERIALS AND METHODS: Epidermal growth factor receptor was assessed by immunohistochemistry as a percentage of positive tumor cells in hot spots (10 high-power fields). The study group comprised of 35 cases of GBM. All cases underwent surgical resection and subsequently underwent radiotherapy (n = 17) or radiotherapy with adjuvant temozolomide chemotherapy (n = 18). Immediate response to therapy was assessed at 3 months using World Health Organization response evaluation criteria in solid tumors criteria and cases followed up for survival. RESULTS: Twenty-four cases (68.6%) expressed EGFR while 11/35 (31.4%) cases were negative. Response to therapy was evident in 21/35 cases (60.0%) and 14/35 were (40.0%) nonresponders. Mean EGFR protein expression in responders was 37.23 +/- 33.70 and in nonresponders was 59.5 +/- 39.46 (P = 0.542). The percentage of responders which were EGFR negative was 72.7% and while response in EGFR positive cases was observed in 54.2%. Mean survival in EGFR positive and negative GBM was 394.37 +/- 189.11 and 420.54 +/- 191.23 days, respectively. CONCLUSION: The EGFR negative cases appear to respond better to therapy, however, the difference is not statistically significant (P = 0.298). Further, EGFR protein expression does not play a definitive role in predicting survival. This is an original study evaluating EGFR in terms of therapeutic response. PMID- 25118730 TI - The prognostic significance of bone marrow metastases: evaluation of 58 cases. AB - BACKGROUND: Bone marrow biopsy is widely used method for diagnosis, follow-up and staging of hemato-oncologic diseases. This procedure is also used for determining the bone marrow metastasis in patients with solid tumors. In this study, clinical, hematological, and pathological features of 58 patients with bone marrow metastases diagnosed by bone marrow biopsies were examined retrospectively MATERIALS AND METHODS: Among 3345 bone marrow biopsies performed in our hospital between January 2006 and August 2013, 58 cases with solid tumor metastasized to bone marrow were included in this study. RESULTS: Among 58 cases with solid organ carcinoma metastasis in bone marrow, mean age was 59.9. Thirty-nine cases were found to have a known primary tumor focus. The most common tumors metastasized to bone marrow were breast carcinomas (23 patients, 59%), gastric carcinomas (6 patients, 15.3%), prostate carcinomas (4 patients, 10,2%), and lung carcinomas (3 patients, 7.7%), respectively. Nineteen patients were firstly diagnosed from bone marrow biopsies as metastatic carcinomas. The median overall survival after bone marrow metastasis was 28 days (95% confidence interval: 7.5-48.4). The median overall survival difference was not statistically significant between patients with primary known and unknown tumor (P = 0.973). Statistically significant difference was observed between the survival of breast cancer and gastric cancer (P = 0.028). The most common hematologic symptom was the coexistence of anemia and thrombocytopenia (31%), thrombocytopenia (27.6%) and anemia (20.7%) alone. The median overall survival difference was statistically significant between patients who have anemia and thrombocytopenia (P < 0.005). CONCLUSION: Bone marrow biopsy is an easily accessible, easily applied, a useful procedure for diagnosing metastatic diseases in patients with hematologic symptoms such as anemia and thrombocytopenia besides being an uncomfortable procedure for patients. Furthermore, it is useful in predicting the prognosis and short survey after diagnosing bone marrow metastasis. PMID- 25118732 TI - Prevalence of extended spectrum beta-lactamase producing uropathogens and their antibiotic resistance profile in patients visiting a tertiary care hospital in central India: Implications on empiric therapy. AB - CONTEXT: Antimicrobial resistance showed by different uropathogens is one of the barricades that might hinder a successful treatment. Detection of extended spectrum beta-lactamase (ESBL) production among uropathogens is an important marker of endemicity. AIMS: The present prospective study was done to identify the trends of uropathogens, to find the prevalence of ESBL isolates and to study the antibiotic resistance profile of the ESBL and non-ESBL uropathogenic isolates. MATERIALS AND METHODS: This study was conducted in the Department of Microbiology of a teaching tertiary care hospital from July 2013 to September 2013. All the uropathogenic isolates were identified up to species level by conventional methods. The prevalence of potential ESBL producers was explored. Antibiotic resistance test of the urinary isolates was done by disc-diffusion method and the results were interpreted according to Clinical Laboratory Standards Institute-2013 guidelines. RESULTS: A total of 670 urine samples from male and female patients visiting the outpatient department (OPD) and inpatient department (IPD) of our hospital were collected. A significantly higher number of IPD and OPD males (55.1% and 55.5%) were found to be culture positive. Escherichia coli (55.3%) was the most frequently isolated uropathogen followed by Klebsiella pneumoniae (23%). However, strains of Escherichia coli (41.6%) were the highest ESBL producing isolates followed by Pseudomonas aeruginosa (36.1%). ESBL producing isolates were found to be multidrug-resistant when compared to non ESBL producers. However, excessive drug-resistance among non-ESBL producing isolates can't be ignored. CONCLUSION: Our study confirms a global trend toward increased resistance to beta-lactam antibiotics. We emphasize on the formulation of antibiotic policy for a particular geographical area. PMID- 25118731 TI - An appraisal of clinicopathological parameters in Japanese encephalitis and changing epidemiological trends in upper Assam, India. AB - CONTEXT: Japanese encephalitis (JE), an acute mosquito-borne viral disease, is one of the leading causes of viral encephalitis in the South-East Asian region. JE is endemic in Assam. The morbidity and mortality due to JE is significant with outbreaks every year during the monsoons. AIMS: The aim was to study the clinicopathological profile of JE; to examine their role in predicting disease outcome; and to document the increase in the incidence of JE among the adult population in this region. MATERIALS AND METHODS: Clinically suspected acute encephalitis syndrome (AES) cases admitted in Assam Medical College and Hospital during the period of May 2011 to April 2012 were tested by JE virus specific Immunoglobulin M capture ELISA. STATISTICAL ANALYSIS USED: Data analysis was performed using SPSS version 16.0. RESULTS: Out of 424 AES cases, 194 were JE positive. The occurrence of JE in adults was higher (P < 0.001) than the pediatric age group. The study recorded a high rate of renal dysfunction in JE cases. A single case of JE induced abortion and two cases of JE neurocysticercosis co-infections were documented. Regression analysis revealed that adult population, unconsciousness, paresis and elevated cerebrospinal fluid protein level were associated with a worse prognosis in JE cases. Mortality in JE positive cases was higher than the JE negative cases (P = 0.001). CONCLUSION: The study attempts to highlight the role played by a combination of clinical and laboratory parameters in assessing the severity and outcome in JE and may help in directing the limited medical resources toward those that need it the most. PMID- 25118733 TI - Comparison of severe pneumonia caused by Human metapneumovirus and respiratory syncytial virus in hospitalized children. AB - OBJECTIVES: The objective of this study is to compare the incidence and clinical characteristics of severe pneumonia caused by Human metapneumovirus (hMPV) to respiratory syncytial virus (RSV) infection in children. PATIENTS AND METHODS: A total of 151 children hospitalized with severe pneumonia, were tested for hMPV using reverse-transcription polymerase chain reaction. At the same time, samples were tested for RSV and other common respiratory viruses. Medical records, including clinical, laboratory data, and chest radiography findings, were reviewed for all children. RESULTS: Of the 151 samples, 88 (58.3%) were positive for respiratory viruses. Of the 88 positive, there were 6 (4.0%) with hMPV, 66 (43.7%) with RSV, 13 (8.6%) with influenza A, 2 (1.3%) with parainfluenza virus III, 1 (0.7%) with parainfluenza virus I, 1 (0.7%) with adenovirus and 1 (0.7%) with influenza B. hMPV-infected patients were significantly older than RSV infected patients (P < 0.001). Children with hMPV pneumonia had fever more frequently (P = 0.03). Two hMPV-positive patients (33.3%) required admission to an intensive care unit, and two patients (33.3%) required mechanical ventilation. The duration of illness was 18.33 +/- 7.09 days. These characteristics of hMPV infections were similar to patients with RSV infections. CONCLUSION: Human metapneumovirus is an infrequent viral pathogen causing severe pneumonia in children. Children with hMPV were older than those with RSV. The disease caused by hMPV was similar in presentation and severity to RSV, with a minority of children requiring additional respiratory support. PMID- 25118734 TI - Prevalence and invasiveness of community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis. AB - BACKGROUND: Reports suggest that the prevalence of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA) has increased, and that CA-MRSA is more virulent than healthcare-associated (HA)-MRSA. AIMS: The aim of this study is to gain a better understanding of the invasiveness and prevalence of CA-MRSA in patients; we systematically reviewed the literature by conducting a meta analysis. MATERIALS AND METHODS: We searched the MEDLINE and PUBMED databases from the year these databases were established to January 2013. RESULTS: The pooled CA-MRSA prevalence among 50,737 patients from 33 studies was 39.0% (range, 30.8-47.8%). The pooled CA-MRSA prevalence rates among pediatric and adult patients with MRSA infection were 50.2% (range, 37.5-62.8%) and 42.3% (range, 16.4-73.3%), respectively. The pooled CA-MRSA prevalence rates of MRSA-infected patients in Asia, Europe, and North America were 23.1% (range, 12.0-39.8%), 37.4% (range, 21.1-56.4%), and 47.4% (range, 35.8-59.4%), respectively. Using the random effects model, we determined that the pooled odds ratio of invasive infections in CA- and HA-MRSA was 0.30 (95% confidence interval: 0.08-1.10; P = 0.07, test for heterogeneity P < 0.00001). CONCLUSIONS: The prevalence of CA-MRSA in MRSA infection varied with area and population. No difference in the ability to cause invasive infections was found between CA- and HA-MRSA. This finding challenges the view that CA-MRSA is more virulent than HA-MRSA. PMID- 25118735 TI - Genotype MTBDR plus assay for molecular detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis. AB - AIM: This study was performed for the rapid identification of Mycobacterium tuberculosis complex and its resistance to rifampicin and isoniazid, directly from the sputum samples of pulmonary tuberculosis patients. MATERIALS AND METHODS: A commercially available genotype MTBDR plus assay was used for the identification and detection of mutations in Mycobacterial isolates. A total of 100 sputum samples of pulmonary tuberculosis patients were analyzed by using the genotype MTBDR plus assay. The MTBDR plus assay is designed to detect the mutations in the hotspot region of rpoB gene, katG and regulatory region of inhA gene. RESULTS: The genotype MTBDR plus assay detected 22% multidrug resistant (MDR), 2% rifampicin (RMP) monoresistant and 1% isoniazid (INH) monoresistant isolates. In 22 MDR isolates, the codons most frequently involved in RMP associated mutations were codon 531 (54.55%), 516 (31.82%) and 526 (13.63%), and 90.90% of MDR isolates showed KatG S315T mutations and 9.1% showed inhA C-15T mutations associated with INH resistance. CONCLUSION: The new genotype MTBDR plus assay represents a rapid, reliable tool for the detection of MDR-TB, wherein results are obtained in 5 h allowing early and appropriate treatment, which is essential to cut the transmission path and reduce the spread of MDR-TB. The genotype MTBDR plus assay can readily be included in a routine laboratory work for the early diagnosis and control of MDR-TB. PMID- 25118736 TI - Phosphatase and tensin analog expression in arterial atherosclerotic lesions. AB - CONTEXT: Phosphatase and tensin analog (PTEN) gene mutation has been proven for pro-inflammatory property and proliferative potential through tyrosine kinase pathway. We studied mutated PTEN for its pathogenetic association in arterial atherosclerosis. AIMS: The objective was to study mutation of PTEN by immunohistochemical method in arterial atherosclerotic lesions and correlate with grades of atherosclerosis, smooth muscle migration in intima, degree of inflammation and Framingham heart study risk factors. SETTINGS AND DESIGN: Human, Prospective Clinical study. MATERIALS AND METHODS: We studied patients with arterial occlusive disease diagnosed by Doppler ultrasonography over a 2-year period. Immunohistochemistry was performed with mouse monoclonal antibodies for PTEN and smooth muscle actin (SMA). STATISTICAL ANALYSIS USED: Chi-square test. RESULTS AND CONCLUSION: Aorta was the single most common vessel affected (21%). Mean age of patients studied was 48.6 years and 80% were male. Mutant PTEN was associated with higher grades of atherosclerotic lesions (P < 0.0001) graded by American Heart Association classification and with smooth muscle proliferation and migration in intima (P < 0.0001). No statistically significant association with the vessel wall inflammation and other risk factors of atherosclerosis. PMID- 25118737 TI - Loss of chromosome Y in acute lymphoblastic leukemia: age related or neoplastic phenomenon? AB - Loss of chromosome Y (LOY) in the bone marrow has long been considered as an age related phenomenon with an incidence of more than 25% in males beyond the age of 80 years. Though reported as an acquired abnormality in myeloid neoplasms, it has rarely been described in B-lymphoblastic leukemia which primarily is a disease of the young. We describe here in three cases of pediatric B-lymphoblastic leukemia with LOY. Conventional cytogenetic studies and fluorescence in situ hybridization studies using centromeric probes for chromosome X and Y on peripheral blood samples ruled out constitutional LOY in all the three cases favoring it to be a neoplastic phenomenon. PMID- 25118738 TI - Role of water quality assessments in hospital infection control: experience from a new oncology center in eastern India. AB - Water quality assessment and timely intervention are essential for health. Microbiology, total dissolved solids (TDS) and free residual chlorine were measured for water quality maintenance in an oncology center in India. Impact of these interventions over a period of 22 months has been demonstrated with four cardinal events. Pseudomonas in hospital water was controlled by adequate chlorination, whereas high TDS in the central sterile supply department water was corrected by the installation of electro-deionization plant. Contaminated bottled water was replaced using quality controlled hospital supply. Timely detection and correction of water-related issues, including reverse osmosis plant was possible through multi-faceted approach to water quality. PMID- 25118739 TI - Observations on Citrobacter species from a tertiary care health center with special reference to multi-drug resistance and presence of CTX-M gene. AB - BACKGROUND: Citrobacter is an important nosocomial pathogen and its multi-drug resistant (MDR) isolates are increasingly being reported across the globe. They are known to produce extended spectrum beta lactamase (ESBL) and harbor CTX-M gene. OBJECTIVE: The aim was to isolate Citrobacter sp. from clinical specimens, analyze their MDR status and look for the presence of CTX-M gene. MATERIALS AND METHODS: In this prospective study, Citrobacter isolates positive for ESBL on screening, were confirmed by combined disc method along with minimum inhibitory concentration (MIC) for cefotaxime. In selected cefotaxime resistant isolates, multiplex polymerase chain reaction was done for blaCTX-M gene. RESULTS: Of 146 Citrobacter sp. isolated, most (73%) were from admitted patients and hospital stay of >72 h and prior antibiotic intake were the most common associated factors. Maximum isolates were from pus (41.1%). Citrobacter freundii was the commonest species (49%) followed by Citrobacter koseri (28%); 79 were ESBL producers. Seventy were cefotaxime resistant as shown by MIC. blaCTX-M gene was detected in 15/40 of these isolates, all belonged to CTX-M group 1. CONCLUSION: Overall incidence of Citrobacter in our setup is low, but they were mostly MDR, and ESBL production was high, which is a cause of concern. blaCTX-M gene detection is important because of its rapid transmission to other bacterial species. PMID- 25118740 TI - Human parvovirus B19 in Iranian pregnant women: a serologic survey. AB - BACKGROUND: Parvovirus B19 infection is associated with clinical symptoms that vary in the spectrum from trivial to severe. The important clinical manifestations are erythema infectiosum or the fifth disease, transient aplastic anemia in patients with hemoglobinopathies, acute polyarthralgia syndrome in adults, hydrops fetalis, spontaneous abortion and stillbirth. Acute infection in nonimmune pregnant women can lead to fetal hydrops. In view of the many complications that can result from acute parvovirus B19 infections during pregnancy, documenting the seroprevalence of anti-parvovirus B19 IgG and its association with the history of abortion in an Iranian population of pregnant women would be of value. MATERIALS AND METHODS: Serum samples from 86 pregnant women were collected between May and September 2011 in West Azerbaijan province of Iran. Every pregnant woman completed a questionnaire which included age, history of tattooing, blood transfusion, and abortion. Anti-B19 specific IgG was detected by using commercial enzyme-linked immunosorbent assays. RESULTS: Anti B19-specific IgG antibody was detected in (65/86, 75.6%) of pregnant women. The mean age was 25.56 +/- 5.30 years and three women had a documented history of blood transfusion (2 of them tested seropositive for B19). 16/18 (88.8%) of women with a history of abortion were IgG positive. The frequency of abortion sessions in the seropositive group (25 sessions of abortion: 11 women experienced once, 2 twice, 2 thrice and one 4 times) was 4.03 times greater than abortion in seronegative group (2 abortions/21 seronegative women). CONCLUSION: Our study reaffirms previous reports regarding the higher frequency of abortion among anti B19 IgG seropositive pregnant women and a possible role of this viral infection in the pathogenesis of abortion. PMID- 25118741 TI - Metastatic ganglioneuroma: a misnomer. AB - Neuroblastoma, ganglioneuroblastoma and ganglioneuroma atumors arising from the neural crest cells. Ganglioneuroma is considered as the most mature amongst the three and usually has no metastatic potential. Spontaneous maturation of neuroblastoma into ganglioneuroma is, however, quite well-known. Here, we present a case of an 8-year-old girl child with evidence of metastasis of ganglioneuroma into a lymph node. PMID- 25118742 TI - Primary extrauterine endometrial stromal sarcoma: Located in pelvic and abdominal tissue and arising in endometriosis. AB - Primary extrauterine endometrial stromal sarcoma is a rare tumor and it is infrequently associated with endometriosis. We are reporting a case of this unusual tumor in a 42-year-old female who presented with multiple nodules of tumor in the abdomen and pelvis and with metastases in para-aortic lymph nodes. The right parametrium, in addition, had a focus of endometriosis, which was contiguous with the tumor, confirming its origin. PMID- 25118743 TI - Leiomyoadenomatoid tumor of the uterus: report of a rare entity and review of the literature. AB - Adenomatoid tumor occurs in the testicular spermatic cord and ejaculatory duct in males and in the fallopian tube and uterus in the females. These are usually small, benign lesions and are mostly incidental findings. Leiomyo-adenomatoid tumor (LMAT) is a variant of adenomatoid tumor, where in the smooth muscle component is predominant. Only nine cases of LMAT are reported so far in the English literature. We report one case and review the nine cases reported so far. PMID- 25118744 TI - Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. AB - Clear cell myomelanocytic tumors (CCMTs) of the falciform ligament/ligamentum teres are extremely rare. CCMTs are a variant of perivascular epithelioid cell tumors. We present a case of hepatic CCMT in a 54-year-old woman with abdominal pain. The patient had an 8.8 cm well-demarcated tumor in the right lobe of the liver. Contrast-enhanced computed tomography showed a heterogeneous mass that enhanced significantly in the arterial and portal venous phases, and was less enhanced in the delayed phase. The patient underwent a right hemihepatectomy and cholecystectomy. The tumor cells had clear to slightly eosinophilic cytoplasm, vesicular nuclei, and were positive for HMB-45 and smooth muscle actin. The patient had no recurrence after 36 months follow-up. A review of the literature identified 10 hepatic CCMTs. Hepatic CCMTs are usually benign tumors of young women that present as large masses located in the right lobe of the liver. PMID- 25118746 TI - Cutaneous myxoma: an important clue to Carney complex. AB - A 22-year-old male became unconscious and was found to have left-sided weakness and facial asymmetry. Previously, he had up to 35 excisions for subcutaneous swellings all over the body, commencing at age 6 years. Examination revealed small nodular skin lesions on the neck, the eyelid and hard palate. Two dimensional echocardiography showed two left atrial masses. Histopathological examination of the subcutaneous lesions showed cutaneous myxomas with a prominent epithelial component. The left atrial masses were also myxomas. The case attempts to highlight the importance of histopathological examination of subcutaneous swellings. Cutaneous and subcutaneous manifestations, including cutaneous myxomas, are among the earliest presentations in Carney's complex and may herald potentially fatal cardiac myxoma. The prominent epithelial component in cutaneous myxomas may be confusing and cause diagnostic difficulties. PMID- 25118745 TI - Clear cell myoepithelial carcinoma ex pleomorphic adenoma. AB - Pleomorphic adenoma is the most common epithelial neoplasm of lacrimal gland. A clear cell myoepithelial carcinoma arising in the background of pleomorphic adenoma is common in the salivary glands but very rare in the lacrimal glands. We report the case of a 27 year old man whose lacrimal gland pleomorphic adenoma recurred several times over a period of four years and ultimately evolved into a clear cell myoepithelial carcinoma ex pleomorphic adenoma. PMID- 25118747 TI - Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma located on gastric high body: two case reports. AB - Lymphoepithelioma-like gastric carcinoma (LELGC) is a rare neoplasm of the stomach with an incidence of 1-4% of all gastric cancers. It is characterized by the presence of a lymphoid stroma with cells arranged primarily in micro alveolar, thin trabecular, and primitive tubular patterns or isolated cells. It is one of the histological patterns observed in patients with Epstein - Barr virus (EBV)-associated gastric carcinoma (EBVaGC). In situ hybridization was usually used to confirm the presence of EBV. There are two types of EBVaGC, LELGC, and ordinary type. Approximately, 15-25% of EBVaGC exhibit the LELGC pattern. Here, we described two cases of LELGC and the related literatures were reviewed as well. The two cases were submucosal mass from a 59- or 63-year-old man. We found LELGC has special clinicopathologic features and protein expression profile. This should promote us to make a true diagnosis. PMID- 25118748 TI - Diagnostic dilemma in myoepithelial carcinoma of cheek. AB - Myoepithelial carcinoma (MC) is a rare neoplasm of the salivary gland generally occurring in the parotid gland and rarely in the minor salivary glands. It poses a diagnostic challenge on fine-needle aspiration (FNA) cytology because it can show different cell types and lack clear features of malignancy. This can lead to a range of differential diagnosis on cytology. The diagnostic difficulty can be compounded if the lesion is present at an unusual site. A 41-year-old male presented with a recurrent swelling on the check since 2 years with a prior history of pleomorphic adenoma (PA) at the same site 8 years back. FNA was performed and a diagnosis of recurrent PA or myoepithelial cell neoplasm was given. Final diagnosis was made on histology and immunohistochemistry studies and reported as MC of minor salivary gland originating within PA. Pathologist should be aware of the occurrence of MC at the sites of the minor salivary glands in the oral cavity and its wide morphologic spectrum to make a confident diagnosis of MC preoperatively. PMID- 25118749 TI - Cytoplasmic-anti-neutrophil cytoplasmic antibodies targeting myeloperoxidase in Wegener's granulomatosis: a rare phenomenon. AB - Wegener's granulomatosis (WG) patients can rarely have antineutrophil cytoplasmic antibodies (ANCAs) directed against myeloperoxidase (MPO), producing a cytoplasmic pattern on indirect immunofluorescence (IIF). This has important implications in the diagnosis and pathophysiology of the disease. We present to you a report of three cases of WG, demonstrating a cytoplasmic-ANCA pattern on indirect IIF, but directed against MPO. It is necessary to diagnose a patient taking into account both the autoimmune test results and the clinical features. PMID- 25118750 TI - Nonhemophilic hemosiderotic synovitis of the knee: a case report and review of literature. AB - Synovium is specialized mesenchymal tissue lining the inner surface of the joint capsule and is the site for a series of pathologic processes that are characteristic, and in some cases specific, to this distinctive tissue. Hemosiderotic synovitis is a rare and inadequately defined synovial proliferative disorder, which develops with recurrent hemorrhages in the joint. The most affected joint from bleeding is the knee whatever the etiology is. Repeated hemarthrosis may produce significant structural alteration of joints leading to chronic osteoarthritis. The most common cause is hereditary clotting factor deficiency diseases like hemophilia. We report a rare case of nonhemophilic hemosiderotic synovitis of the knee joint, in which the patient lacks history of any bleeding diathesis. Its definitive diagnosis was possible only by histopathological examination. The prompt recognition of this distinct subtype of hemosiderotic synovitis and awareness of underlying causes should lead to earlier diagnosis, appropriate therapy, less joint destruction, and better outcomes. PMID- 25118751 TI - Spurious platelet count due to cryoglobulins in a patient with smoldering myeloma. AB - Use of automated hematology analyzers for routine blood count reporting has increased the reproducibility and accuracy of test results. However, at times, these instruments may generate spurious test results. Such results can result in inappropriate investigations or treatment decisions in patients. Spuriously normal or high platelet counts carry the risk of under diagnosis of the true thrombocytopenia with adverse clinical implications. We present a patient with smoldering myeloma with spurious platelet count due to cryoglobulins. PMID- 25118752 TI - Omental sclerosing extramedullary hematopoietic tumors in Janus kinase-2 negative myelofibrosis: caveat at frozen section. AB - Sclerosing extramedullary hematopoietic tumors (SEMHTs) are associated with chronic myeloproliferative neoplasms. These extremely rare mass lesions were first described in kidney and peritoneum. On histopathology, they are characterized by sclerosis, entrapped fat, atypical megakaryocytes with myeloid and erythroid elements. Only approximately ten cases have been subsequently reported in orbit, lacrimal system, liver, omentum, and skin. The authors present a case of SEMHTs as incidentally detected omental nodules, while the patient was undergoing splenectomy for Janus kinase-2 negative myelofibrosis. The authors postulate their origin in omentum-associated lymphoid tissue; and highlight the diagnostic dilemma presented by SEMHTs at frozen section. PMID- 25118753 TI - Aggressive natural killer-cell leukemia: classical presentation of a rare disease. AB - Aggressive natural killer-cell leukaemia is a rare aggressive form of natural killer-cell neoplasm. We report a case of a 40-year-old male who presented with jaundice, raised blood counts,generalised lymphadenopathy and hepatosplenomegaly. The diagnosis was established by flow cytometric analysis of bone marrow aspirate. The patient, however, succumbed to his illness within 2 weeks of starting chemotherapy. To the best of our knowledge, this is the third reported case from India. PMID- 25118754 TI - Hospital acquired urinary tract infection by multidrug-resistant Brevundimonas vesicularis. AB - Infections caused by Brevundimonas vesicularis, a nonfermenting Gram-negative bacterium, are very rare. Here, we report the first case of multidrug-resistant hospital acquired urinary tract infection by B. vesicularis. Patient was successfully treated with antimicrobial therapy with piperacillin-tazobactam and amikacin. PMID- 25118755 TI - Extended spectrum beta lactamase producing Proteus penneri: a rare missed pathogen? AB - Indole negative Proteus species are invariably incorrectly identified as Proteus mirabilis, often missing out isolates of Proteus penneri. We report a case of extended spectrum beta lactamase producing and multidrug-resistant P. penneri isolated from pus from pressure sore of a patient of road traffic accident. Correct and rapid isolation and identification of such resistant pathogen are important as they are significant nosocomial threat. PMID- 25118756 TI - Massive pleural effusion due to paragonimiasis: biochemical, cytological, and parasitological findings. AB - Paragonimiasis is an important food-borne parasitic zoonosis caused by trematode species of the genus, Paragonimus occurring in many parts of the world except in Australia and Antarctica. In India, it is an emerging parasitic disease, which is endemic in the northeast states where people have a common practice of eating raw or inadequately cooked freshwater crabs. In these states, Paragonimus heterotremus has been identified as the major causative agent of the human paragonimiasis. The most common clinical form of the disease is pulmonary paragonimiasis; however, extra-pulmonary manifestations are not uncommon. Here, we report a case of primary massive unilateral pleural effusion due to paragonimiasis. The diagnosis was confirmed by finding Paragonimus ova in the pleural fluid. The patient was successfully treated with repeated thoracocentesis and a course of praziquantel. PMID- 25118757 TI - Panoramic images of testicular feminizing syndrome. PMID- 25118758 TI - Intrathoracic extramedullary hematopoiesis in E-beta thalassemia. PMID- 25118759 TI - Cutaneous images of interest of fascioliasis from India. PMID- 25118760 TI - Quiz 3/2014. PMID- 25118761 TI - Quiz 4/2014. PMID- 25118762 TI - Mucosa associated lymphoid tissue lymphoma of gallbladder: a rare presentation. PMID- 25118763 TI - Paratesticular myxofibrosarcoma. PMID- 25118764 TI - Calcifying fibrous tumor of the rectum: a case report. PMID- 25118765 TI - Barium granuloma mimicking carcinoma rectum: an unusual presentation. PMID- 25118766 TI - Nodal metastatic, undifferentiated nasopharyngeal carcinoma and classical Hodgkin lymphoma: age old mimics. PMID- 25118767 TI - Gastric glomus tumor: a brief report. PMID- 25118768 TI - Solitary angiokeratoma of tongue: a rare entity clinically mistaken as a malignant tumor. PMID- 25118769 TI - Relevance of synovial cells in gouty tophus on fine needle aspiration cytology. PMID- 25118770 TI - Acute megakaryoblastic leukemia M7 presenting with extreme myelofibrosis. PMID- 25118771 TI - Histological identification of Entomophthoromycosis in biopsy samples is required. PMID- 25118772 TI - Intestinal spirochetosis: a disease or an interesting finding. PMID- 25118773 TI - Commentary on intestinal spirochetosis. PMID- 25118774 TI - Comparison of Clinical and Laboratory Standards Institute 2008 and 2010 guidelines in interpreting susceptibility of enterobacteriaceae isolates. PMID- 25118775 TI - Isolated nasal chromoblastomycosis. PMID- 25118776 TI - Aeromonas species isolated from a case of meningitis. PMID- 25118777 TI - Spectrum of lymph node pathology: inadequate data, challenging issues. PMID- 25118778 TI - Slide seminars: is it the right way to test the students' surgical pathology knowledge? PMID- 25118779 TI - Vaccination management and vaccination errors: a representative online-survey among primary care physicians. AB - BACKGROUND: Effective immunizations require a thorough, multi-step process, yet few studies comprehensively addressed issues around vaccination management. OBJECTIVES: To assess variations in vaccination management and vaccination errors in primary care. METHODS: A cross sectional, web-based questionnaire survey was performed among 1157 primary physicians from North Rhine-Westphalia, Germany: a representative 10% random sample of general practitioners (n = 946) and all teaching physicians from the University Duisburg-Essen (n = 211). Four quality aspects with three items each were included: patient-related quality (patient information, patient consent, strategies to increase immunization rates), vaccine related quality (practice vaccine spectrum, vaccine pre-selection, vaccination documentation), personnel-related quality (recommendation of vaccinations, vaccine application, personnel qualification) and storage-related quality (storage device, temperature log, vaccine storage control). For each of the four quality aspects, "good quality" was reached if all three criteria per quality aspect were fulfilled. Good vaccination management was defined as fulfilling all twelve items. Additionally, physicians' experiences with errors and nearby-errors in vaccination management were obtained. RESULTS: More than 20% of the physicians participated in the survey. Good vaccination management was reached by 19% of the practices. Patient-related quality was good in 69% of the practices, vaccine related quality in 73%, personnel-related quality in 59% and storage-related quality in 41% of the practices. No predictors for error reporting and good vaccination management were identified. CONCLUSIONS: We identified good results for vaccine- and patient-related quality but need to improve issues that revolve around vaccine storage. PMID- 25118781 TI - Deep penetrating nevus-like borderline tumors: A unique subset of ambiguous melanocytic tumors with malignant potential and normal cytogenetics. AB - BACKGROUND: Deep penetrating nevi (DPN) are a relatively uncommon subtype of melanocytic nevi. A small subset of these lesions exhibit atypical features (cytologic and architectural atypia, mitotic activity) seen in melanoma. These lesions we term the deep penetrating nevus-like borderline tumor. Unequivocal melanomas can show overlapping morphologic features of DPN, which have been termed plexiform melanomas. PATIENTS AND METHODS: 40 cases of DPN-like borderline tumor were identified along with 6 cases of plexiform melanoma. Clinical follow up was obtained, along with cytogenetic analysis in the form of fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization (CGH). RESULTS: The DPN-like borderline tumor cases included 24 females and 16 males. Of sentinel lymph node biopsies performed, 1/3 of cases showed lymph node involvement. All patients where an aggressive clinical approach was adopted remain free of disease. All 6 DPN-like borderline tumor cases tested by CGH showed normal cytogenetics, as did 7 of 9 cases tested by FISH. Of the plexiform melanomas, 4/6 patients died of disease. In 3 cases there was morphologic progression from a DPN-like borderline tumor to overt melanoma. In one case of progression, cytogenetics was normal in the DPN-like borderline tumor and then abnormal in the progressed melanoma. CONCLUSION: DPN-like borderline tumors are melanocytic tumors associated with a high incidence of regional lymph node disease and exhibiting the potential for melanoma progression despite a normal cytogenetic profile. Patients with these lesions should be aggressively managed, with at least complete re-excision and consideration of sentinel node biopsy, regardless of cytogenetic data. PMID- 25118782 TI - Preventive effects of Escherichia coli strain Nissle 1917 with different courses and different doses on intestinal inflammation in murine model of colitis. AB - OBJECTIVE: To analyze the in vivo effect of Escherichia coli Nissle 1917 (EcN) with different courses and different doses to Sprague-Dawley rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: The probiotic was orally administered with different courses of treatment (with or without pre administration) and different doses (10(7)-10(9) CFU/day) to Sprague-Dawley rats with TNBS-induced colitis. Therapeutic effects, levels of cytokine in serum, mRNA and protein expression were analyzed. RESULTS: Oral EcN administration after TNBS induced improved colitis dose dependently. In parallel, a reduction of disease activity index and colonic MPO activity together with a decreased level of TNF alpha and a trend of increased IL-10 expression was detected. Pre-administration of 10(7)CFU/day EcN to TNBS-treated rats resulted in a significant protection against inflammatory response and colons isolated from these rats exhibited a more pronounced expression of ZO-1 than the other groups. In the group of pre administration of 10(9)CFU/day, the condition was not improved but deteriorated. CONCLUSIONS: This study convincingly demonstrates that pre-administration of probiotic EcN with low dose is able to protect colitis of rats and mediate up regulation of ZO-1 expression, but long-term of high-dose EcN may do harm to colitis. PMID- 25118785 TI - Relevance of intracellular polarity to accuracy of eukaryotic chemotaxis. AB - Eukaryotic chemotaxis is usually mediated by intracellular signals that tend to localize at the front or back of the cell. Such intracellular polarities frequently require no extracellular guidance cues, indicating that spontaneous polarization occurs in the signal network. Spontaneous polarization activity is considered relevant to the persistent motions in random cell migrations and chemotaxis. In this study, we propose a theoretical model that connects spontaneous intracellular polarity and motile ability in a chemoattractant solution. We demonstrate that the intracellular polarity can enhance the accuracy of chemotaxis. Chemotactic accuracy should also depend on chemoattractant concentration through the concentration-dependent correlation time in the polarity direction. Both the polarity correlation time and the chemotactic accuracy depend on the degree of responsiveness to the chemical gradient. We show that optimally accurate chemotaxis occurs at an intermediate responsiveness of intracellular polarity. Experimentally, we find that the persistence time of randomly migrating Dictyostelium cells depends on the chemoattractant concentration, as predicted by our theory. At the optimum responsiveness, this ameboid cell can enhance its chemotactic accuracy tenfold. PMID- 25118783 TI - TLR4 inhibition impairs bacterial clearance in a therapeutic setting in murine abdominal sepsis. AB - OBJECTIVE AND DESIGN: To investigate the therapeutic effect of E5564 (a clinically used TLR4 inhibitor) in murine abdominal sepsis elicited by intraperitoneal infection with a highly virulent Escherichia coli in the context of concurrent antibiotic therapy. METHODS: Mice were infected with different doses (~2 * 10(4)-2 * 10(6) CFU) of E. coli O18:K1 and treated after 8 h with ceftriaxone 20 mg/kg i.p. combined with either E5564 10 mg/kg i.v. or vehicle. For survival studies this treatment was repeated every 12 h. Bacterial loads and inflammatory parameters were determined after 20 h in peritoneal lavage fluid, blood, liver and lung tissue. Plasma creatinin, AST, ALT and LDH were determined to assess organ injury. RESULTS: E5564 impaired bacterial clearance under the antibiotic regime after infection with a low dose E. coli (1.7 * 10(4) CFU) while renal function was slightly preserved. No differences were observed in bacterial load and organ damage after infection with a tenfold higher (1.7 * 10(5) E. coli) bacterial dose. While treatment with E5564 slightly attenuated inflammatory markers provoked by the sublethal doses of 104-105 E. coli under the antibiotic regime, it did not affect lethality evoked by infection with 1.7 * 106 E. coli. CONCLUSIONS: The impact of TLR4 inhibition during abdominal sepsis by virulent E. coli bacteria is only beneficial at low infection grade at cost of bactericidal activity. PMID- 25118786 TI - Joep MA Lange. PMID- 25118784 TI - Blockade of proteinase-activated receptor 4 inhibits neutrophil recruitment in experimental inflammation in mice. AB - OBJECTIVE AND DESIGN: The activation of proteinase-activated receptors (PARs) has been implicated in the development of important hallmarks of inflammation, including in vivo leukocyte recruitment; however, its role in the regulation of leukocyte migration in response to inflammatory stimuli has not been elucidated until now. Here, we examined the effects of the PAR4 antagonist YPGKF-NH 2 (tcY NH2) on neutrophil recruitment in experimentally induced inflammation. METHODS: BALB/c mice were intrapleurally injected with tcY-NH2 (40 ng/kg) prior to intrapleural injection of carrageenan (Cg) or neutrophil chemoattractant CXCL8; the number of infiltrating neutrophils was evaluated after 4 h, and KC production was assessed at different times after Cg injection. Neutrophil adhesion and rolling cells were studied using a brain circulation preparation 4 h after the Cg or CXCL8 challenge in tcY-NH2-treated mice. RESULTS: PAR4 blockade inhibited CXCL8- and Cg-induced neutrophil migration into the pleural cavity of BALB/c mice and reduced neutrophil rolling and adherence. Surprisingly, PAR4 blockade increased the level of KC in response to carrageenan. CONCLUSION: These results demonstrated that PAR4 blockade impairs neutrophil migration in vivo, suggesting that PAR4 plays an important role in the regulation of inflammation, at least in part because of its ability to inhibit the actions of the neutrophil chemoattractant CXCL8. PMID- 25118787 TI - A monoclonal antibody against PMEL. AB - PMEL, also known as Pmel17 or gp100, is a melanocyte-specific glycoprotein that is essential for the formation of stage II melanosomes. As it has a highly restricted expression pattern in normal tissues and a transient presence on the cell surface, PMEL is believed to be a potential target for antibody drug conjugate therapy in some pigmentary diseases. The production of a high specificity and high affinity monoclonal antibody against human PMEL was helpful for the antibody drug conjugate therapy study. In the present study, monoclonal antibodies (MAbs) against PMEL were obtained by immunizing BALB/c mice with the recombinant PMEL-GST fusion protein. Three mAbs (A3F, G11B, and J7E) with a titer of 1:6000, 1:10,000, and 1:3000, respectively, were obtained. Immunoglobulin subclass assay revealed that A3F was IgG2b, G11B was IgG1, and J7E was IgG2a. Specificity analysis by Western blotting demonstrated that A3F and J7E cross reacted with GPNMB or LAMP; however, G11B reacted with PMEL only. Immunohistochemistry experiments showed that G11B could bind human PMEL antigen in normal skin. Flow cytometry assay demonstrated that G11B could bind to the surface of PMEL positive melanoma cells but not PMEL negative cells. Taken together, these results show that this G11B provides a useful tool for the antibody drug conjugate therapy study in some pigmentary diseases. PMID- 25118788 TI - Vitamin D status among children and adolescents on anticonvulsant drugs in southern Switzerland. AB - INTRODUCTION: It is recognised that vitamin D status is often inadequate (<50 nmol/l) in epileptic children, mainly because some anticonvulsant drugs induce the enzymes responsible for its metabolism. The purpose of the present study was to address vitamin D status among children and adolescents treated with anticonvulsant drugs and control subjects who reside in southern Switzerland, a high solar radiation region. METHODS: Between January and May 2013, total serum 25-hydroxyvitamin D was assessed by liquid chromatography-tandem mass spectrometry in 58 children and adolescents with epilepsy and 29 controls residing in southern Switzerland. Dark-skinned individuals, females wearing dress styles covering practically the whole body and subjects with body mass index >=85th percentile for age and sex were excluded. RESULTS: Concentration of serum 25-hydroxyvitamin D was similar in epilepsy patients (48 [37-62] nmol/l; median and interquartile range) and controls (53 [47-64] nmol/l). An inadequate serum 25 hydroxyvitamin D concentration was common both among patients (55%) and control subjects (34%). Serum 25-hydroxyvitamin D was significantly lower among patients treated with anticonvulsant drugs that induce the metabolism of vitamin D (30 [21 51] nmol/l) than among the remaining patients (51 [40-65] nmol/l) and controls. CONCLUSIONS: The present study indicates a relevant tendency towards inadequate vitamin D status among children with and without anticonvulsant drug management who reside in southern Switzerland. This tendency is more prominent in patients treated with anticonvulsant drugs that induce the metabolism of 25-hydroxyvitamin D. PMID- 25118789 TI - The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study. AB - Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a "main stream" pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. In a single-dose, open-label study, patients inhaled a single 15.1 +/- 0.1 mg dose of cannabis using the Syqe Inhaler device. Blood samples for Delta(9) tetrahydrocannabinol (THC) and 11-hydroxy-Delta(9)-THC were taken at baseline and up to 120 minutes. Pain intensity (0-10 VAS), adverse events, and satisfaction score were monitored following the inhalation. A uniform pharmacokinetic profile was exhibited across all participants (Delta(9)-THC plasma Cmax +/- SD was 38 +/- 10 ng/mL, Tmax +/- SD was 3 +/- 1 minutes, AUC0->infinity +/- SD was 607 +/- 200 ng.min/mL). Higher plasma Cmax increase per mg Delta(9)-THC administered (12.3 ng/mL/mg THC) and lower interindividual variability of Cmax (25.3%), compared with reported alternative modes of THC delivery, were measured. A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Delta(9)-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs. PMID- 25118790 TI - Failure of dabigatran and rivaroxaban to prevent thromboembolism in antiphospholipid syndrome: a case series of three patients. AB - Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K antagonists (VKA) for the treatment of patients with antiphospholipid syndrome (APS). In the absence of prospective, randomised trial data, reports of therapeutic failures in clinical practice alert clinicians to potential limitations of DOFI therapy for this indication. Data for all cases were collected from a centralised system that contains complete medical records of all patients treated and followed at Mayo Medical Center. We present here three consecutive APS patients who had had no thromboembolism recurrence on warfarin but were switched to DOFIs. The diagnosis of APS was established according to currently recommended criteria. The three cases were as follows: A woman with primary APS developed thrombotic endocarditis with symptomatic cerebral emboli after transition to dabigatran. A second woman with primary APS experienced ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric venous thrombosis after switching to rivaroxaban. None of these patients had failed warfarin prior to the transition to DOFIs. Based on these three cases, we advocate caution in using DOFIs for APS patients outside of a clinical trial setting, until further data becomes available. PMID- 25118791 TI - Acquisition of the stop-spirant alternation in bilingual Mexican Spanish-English speaking children: theoretical and clinical implications. AB - The purpose of this study was to identify characteristics of typical acquisition of the Mexican Spanish stop-spirant alternation in bilingual Spanish-English speaking children and to shed light on the theoretical debate over which sound is the underlying form in the stop-spirant allophonic relationship. We predicted that bilingual children would acquire knowledge of this allophonic relationship by the time they reach age 5;0 (years;months) and would demonstrate higher accuracy on the spirants, indicating their role as the underlying phoneme. This quasi-longitudinal study examined children's single word samples in Spanish from ages 2;4-8;2. Samples were phonetically transcribed and analyzed for accuracy, substitution errors and acoustically for intensity ratios. Bilingual children demonstrated overall higher accuracy on the voiced stops as compared to the spirants. Differences in substitution errors across ages were found and acoustic analyses corroborated perceptual findings. The clinical implication of this research is that bilingual children may be in danger of overdiagnosis of speech sound disorders because acquisition of this allophonic rule in bilinguals appears to differ from what has been found in previous studies examining monolingual Spanish speakers. PMID- 25118792 TI - Metformin combined with p38 MAPK inhibitor improves cisplatin sensitivity in cisplatin-resistant ovarian cancer. AB - The aim of the present study was to determine the effects of metformin, combined with a p38 mitogen-activated protein kinase (MAPK) inhibitor, on the sensitivity of cisplatin-resistant ovarian cancer to cisplatin. The expression and distribution of phosphorylated p38 MAPK (P-p38 MAPK) was confirmed in drug resistant and primary ovarian cancer tissues by immunohistochemistry and western blotting. A bromodeoxyuridine ELISA kit was used to analyze the effects of metformin, SB203580, a p38 MAPK inhibitor, and metformin combined with SB203580, on the cell proliferation of SKOV3/DDP cisplatin-resistant ovarian cancer cells. The protein expression of P-p38 MAPK was significantly higher in cisplatin resistant ovarian cancer, as compared with the primary ovarian cancer tissues. Metformin combined with SB203580 significantly enhanced the sensitivity of SKOV3/DDP cells to cisplatin. In conclusion, the p38 MAPK signaling pathway may be associated with cisplatin-resistant ovarian cancer. Metformin, combined with the p38 MAPK inhibitor, significantly increased the sensitivity of SKOV3/DDP cells to cisplatin treatment. PMID- 25118793 TI - Proteinuria is associated with neurocognitive impairment in antiretroviral therapy treated HIV-infected individuals. AB - BACKGROUND: Proteinuria is a marker of vascular dysfunction that predicted increased cardiovascular mortality and is associated with neurocognitive impairment (NCI) in population-based studies. We examined associations between proteinuria and HIV-associated NCI. METHODS: Multivariable logistic regression was used to examine associations between NCI at the first neurocognitive assessment (baseline) and simultaneous, clinically significant proteinuria [as random spot urine protein-to-creatinine ratios (UP/Cr) >=200 mg/g] in a prospective multicenter observational cohort study. Generalized estimating equations were used to examine associations between baseline proteinuria and subsequent NCI among subjects without NCI at baseline. NCI was defined as a Z score, derived from the combination of normalized scores from the Trailmaking A and B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol tests. RESULTS: A total of 1972 subjects were included in this analysis. Baseline proteinuria was associated with increased odds of NCI [odds ratio (OR): 1.41, 95% confidence interval (CI): 1.08 to 1.85; P = 0.01] and with subsequent NCI among subjects without NCI at baseline (OR: 1.39, 95% CI: 1.01 to 1.93; P = 0.046) in multivariable models adjusted for risk factors and potential confounders. Similar associations were evident when these analyses were limited to visits at which time study subjects maintained plasma HIV RNA levels <200 copies per milliliter. CONCLUSIONS: The association between proteinuria and NCI observed in this study adds to a growing body of evidence implicating contributions by vascular disease to NCI in antiretroviral treated individuals. Studies examining interventions that improve vascular function are warranted. PMID- 25118794 TI - Feasibility and preliminary efficacy of a web-based smoking cessation intervention for HIV-infected smokers: a randomized controlled trial. AB - OBJECTIVE: To evaluate the feasibility and preliminary efficacy of a Web-based tobacco treatment for persons living with HIV (PLWH). DESIGN: Prospective, randomized controlled trial. SETTING: HIV-care center in the Bronx, New York. SUBJECTS: Eligibility criteria included HIV infection, current tobacco usage, interest in quitting, and access to a computer with internet. One hundred thirty eight subjects enrolled, and 134 completed the study. INTERVENTION: Positively Smoke Free on the Web (PSFW), an 8-session, 7-week targeted tobacco treatment program for PLWH, was compared with standard care (brief advice to quit and self help brochure). All subjects were offered nicotine patches. MAIN OUTCOME MEASURES: The main feasibility outcomes were number of sessions logged into, number of Web pages visited, number of interactive clicks, and total time logged in. The main efficacy outcome was biochemically verified, 7-day point prevalence abstinence 3 months after intervention. RESULTS: PSFW subjects logged into a mean of 5.5 of 8 sessions and 26.2 of 41 pages. They executed a mean of 10 interactive clicks during a mean total of 59.8 minutes logged in. Most required reminder phone calls to complete the sessions. Educational level, anxiety score, and home access of the Web site were associated with Web site usage. Ten percent of the PSFW group vs. 4.3% of controls achieved the abstinence end point. Among those who completed all 8 sessions, 17.9% were abstinent, and among women completers, 30.8% were abstinent. CONCLUSIONS: Web-based treatment is a feasible strategy for PLWH smokers, and preliminary findings suggest therapeutic efficacy. PMID- 25118796 TI - Preventing tuberculosis among HIV-infected pregnant women in Lesotho: the case for rolling out active case finding and isoniazid preventive therapy. AB - BACKGROUND: The Lesotho Ministry of Health issued guidelines on active case finding (ACF) for tuberculosis (TB) and isoniazid preventive therapy (IPT) in April 2011. ACF has been recommended in maternal and child health (MCH) settings globally, however, the feasibility of implementing IPT within MCH in countries with high concurrent HIV and TB epidemics is unknown. DESIGN/METHODS: The study evaluated the implementation of ACF and IPT guidelines in MCH settings in 2 health facilities in Lesotho. This descriptive prospective study analyzed data collected during routine services. Categorical data and continuous variables were summarized using descriptive statistics. The chi test or Wilcoxon rank-sum test was used to ascertain significant associations between categorical and continuous variables, respectively. RESULTS: Data from 160 HIV-positive and 640 HIV-negative women were reviewed. Within this study population, 99.8% of women were screened for TB, and 11.4% HIV-positive women compared with 2.3% HIV-negative women were reported to have symptoms of TB (P < 0.001). IPT was initiated in 124/158 (78.5%) HIV-positive pregnant women, 64.5% women completed a 6-month IPT regimen, 2 (1.6%) died of causes unrelated to IPT/TB, and 31.5% were lost to follow-up. Predictors of IPT initiation among HIV-positive women included gestational age at the first antenatal visit (unadjusted odds ratio, -0.93; 95% confidence interval: -0.88 to 0.98), and receipt of antiretroviral therapy for treatment rather than for prevention of mother-to-child transmission prophylaxis only (odds ratio, 4.59; 95% confidence interval: 1.32 to 15.93). CONCLUSIONS: Implementation of ACF and IPT is feasible within the MCH setting. Uptake of IPT during pregnancy among HIV-positive women was high, but with a high rate of loss to follow-up. PMID- 25118797 TI - Metabotropic glutamate receptor 5 as a potential therapeutic target in Huntington's disease. AB - INTRODUCTION: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino terminal region of the huntingtin (htt) protein, which underlies the loss of striatal and cortical neurons. Glutamate has been implicated in a number of neurodegenerative diseases, and several studies suggest that the metabotropic glutamate receptor 5 (mGluR5) may represent a target for the treatment of HD. AREAS COVERED: The main goal of this review is to discuss the current data in the literature regarding the role of mGluR5 in HD and evaluate the potential of mGluR5 as a therapeutic target for the treatment of HD. mGluR5 is highly expressed in the brain regions affected in HD and is involved in movement control. Moreover, mGluR5 interacts with htt and mutated htt profoundly affects mGluR5 signaling. However, mGluR5 stimulation can activate both neuroprotective and neurotoxic signaling pathways, depending on the context of activation. EXPERT OPINION: Although the data published so far strongly indicate that mGluR5 plays a major role in HD-associated neurodegeneration, htt aggregation and motor symptoms, it is not clear whether mGluR5 stimulation can diminish or intensify neuronal cell loss and HD progression. Thus, future experiments will be necessary to further investigate the outcome of drugs acting on mGluR5 for the treatment of neurodegenerative diseases. PMID- 25118795 TI - High medication adherence during periconception periods among HIV-1-uninfected women participating in a clinical trial of antiretroviral pre-exposure prophylaxis. AB - INTRODUCTION: Pre-exposure prophylaxis (PrEP) may be an important safer conception strategy for HIV-1-uninfected women with HIV-1-infected partners. Understanding medication adherence in this population may inform whether PrEP is a feasible safer conception strategy. METHODS: We evaluated predictors of pregnancy and adherence to study medication among HIV-1-uninfected women enrolled in a randomized placebo-controlled trial of PrEP among African HIV-1 serodiscordant couples. Participants were counseled on HIV-1 risk reduction, contraception, and adherence and tested for pregnancy at monthly study visits. Pill counts of dispensed drug were performed and, at a subset of visits, plasma was collected to measure active drug concentration. RESULTS: Among 1785 women, pregnancy incidence was 10.2 per 100 person-years. Younger age, not using contraception, having an additional sexual partner, and reporting unprotected sex were associated with increased likelihood of pregnancy. Monthly clinic pill counts estimated that women experiencing pregnancy took 97% of prescribed doses overall, with at least 80% pill adherence for 98% of study months, and no difference in adherence in the periconception period compared with previous periods (P = 0.98). Tenofovir was detected in plasma at 71% of visits where pregnancy was discovered. By multiple measures, adherence was similar for women experiencing and not experiencing pregnancy (P >= 0.1). CONCLUSIONS: In this clinical trial of PrEP, pregnancy incidence was 10% per year despite excellent access to effective contraception. Women experiencing pregnancy had high medication adherence, suggesting that PrEP may be an acceptable and feasible safer conception strategy for HIV-1-uninfected women with HIV-1-serodiscordant partners. PMID- 25118799 TI - Two new drugs for skin and skin structure infections. PMID- 25118800 TI - Sucroferric oxyhydroxide (Velphoro) for hyperphosphatemia. PMID- 25118798 TI - Effects of high mobility group protein box 1 and toll like receptor 4 pathway on warts caused by human papillomavirus. AB - Accumulative evidence has demonstrated that inflammation has an important role in human papillomavirus (HPV) oncogenicity. However, the effects of high mobility group protein box 1 (HMGB1)-toll like receptor 4 (TLR4) signaling pathway associated inflammation on epidermal warts caused by HPV remain unclear. The present study investigated the HMGB1, TLR4 and nuclear factor-kappaB p65 expression in condyloma acuminatum (CA) and verruca vulgaris (VV). Immunohistochemistry and western blot analysis revealed that p65 expression in epithelial nuclei in VV and CA was significantly higher than in normal skin (NS) (P<0.01), and p65 in CA was higher than in VV but this difference was not significant. The level of extracellular HMGB1 increased significantly and progressively from NS to VV to CA (P<0.05). The level of TLR4 on the surface of epithelial membranes in the CA samples was significantly higher than in NS (P<0.01), and TLR4 in VV samples was significantly lower than in NS (P<0.01). There was a positive correlation between p65 expression in the epithelial nuclei and HMGB1 in the epithelial intercellular spaces (r=0.5199, P<0.01). These findings indicate that inflammation is intensified in warts caused by HPV. HMGB1 TLR4 pathway-associated inflammation may therefore have a pivotal role in CA. HMGB1, rather than TLR4, may be a vital mediator of inflammation in VV. Therapies targeting HMGB1 may be a potential strategy for the treatment of HPV-associated warts. PMID- 25118801 TI - Glycerol phenylbutyrate (Ravicti) for urea cycle disorders. PMID- 25118802 TI - A transcutaneous electrical nerve stimulation device (Cefaly) for migraine prevention. PMID- 25118803 TI - Accumulated knowledge and prevention practices in oral health. AB - This text begins by reflecting on health promotion and equity/ inequity. In health, inequity is understood as a political concept that has moral implications and that is committed to social justice. A discussion follows on some issues regarding the risk and prevention of diseases, still considered a hegemonic practice, and lack of experience in oral health-care, bearing in mind the concept of vulnerability. The risk is probabilistic and involves the mathematical chances of acquiring a disease in a certain group, whereas vulnerability addresses the potential of acquiring or not acquiring a disease in a certain environment. The need for systematic studies on determinants is stressed, with the ultimate goal of improving health and reducing inequities, and with the concern and political intention of including health equity in governmental policies. PMID- 25118804 TI - Presence of a plant-like proton-translocating pyrophosphatase in a scuticociliate parasite and its role as a possible drug target. AB - The proton-translocating inorganic pyrophosphatases (H(+)-PPases) are primary electrogenic H(+) pumps that derive energy from the hydrolysis of inorganic pyrophosphate (PPi). They are widely distributed among most land plants and have also been found in several species of protozoan parasites. Here we describe, for the first time, the molecular cloning and functional characterization of a gene encoding an H(+)-pyrophosphatase in the protozoan scuticociliate parasite Philasterides dicentrarchi, which infects turbot. The predicted P. dicentrarchi PPase (PdPPase) consists of 587 amino acids of molecular mass 61.7 kDa and an isoelectric point of 5.0. Several motifs characteristic of plant vacuolar H(+) PPases (V-H(+)-PPases) were also found in the PdPPase, which contains all the sequence motifs of the prototypical type I V-H(+)-PPase from Arabidopsis thaliana vacuolar pyrophosphatase type I (AVP1) plant. The PdPPase has a characteristic residue that determines strict K(+)-dependence, but unlike AVP1, PdPPase contains an N-terminal signal peptide (SP) sequence. Antibodies generated by vaccination of mice with a genetic or recombinant protein containing a partial sequence of the PdPPase and a common motif with the polyclonal antibody PABHK specific to AVP1 recognized a single band of about 62 kDa in western blots. These antibodies specifically stained both vacuole and the alveolar membranes of trophozoites of P. dicentrarchi. H+ transport was partially inhibited by the bisphosphonate pamidronate (PAM) and completely inhibited by NaF. The bisphosphonate PAM inhibited both H+-translocation and gene expression. PdPPase and PAM also inhibited in vitro growth of the ciliates. The apparent lack of V-H(+)-PPases in vertebrates and the parasite sensitivity to PPI analogues may provide a molecular target for developing new drugs to control scuticociliatosis. PMID- 25118805 TI - Wind farm facilities in Germany kill noctule bats from near and far. AB - Over recent years, it became widely accepted that alternative, renewable energy may come at some risk for wildlife, for example, when wind turbines cause large numbers of bat fatalities. To better assess likely populations effects of wind turbine related wildlife fatalities, we studied the geographical origin of the most common bat species found dead below German wind turbines, the noctule bat (Nyctalus noctula). We measured stable isotope ratios of non-exchangeable hydrogen in fur keratin to separate migrants from local individuals, used a linear mixed-effects model to identify temporal, spatial and biological factors explaining the variance in measured stable isotope ratios and determined the geographical breeding provenance of killed migrants using isoscape origin models. We found that 72% of noctule bat casualties (n = 136) were of local origin, while 28% were long-distance migrants. These findings highlight that bat fatalities at German wind turbines may affect both local and distant populations. Our results indicated a sex and age-specific vulnerability of bats towards lethal accidents at turbines, i.e. a relatively high proportion of killed females were recorded among migratory individuals, whereas more juveniles than adults were recorded among killed bats of local origin. Migratory noctule bats were found to originate from distant populations in the Northeastern parts of Europe. The large catchment areas of German wind turbines and high vulnerability of female and juvenile noctule bats call for immediate action to reduce the negative cross-boundary effects of bat fatalities at wind turbines on local and distant populations. Further, our study highlights the importance of implementing effective mitigation measures and developing species and scale-specific conservation approaches on both national and international levels to protect source populations of bats. The efficacy of local compensatory measures appears doubtful, at least for migrant noctule bats, considering the large geographical catchment areas of German wind turbines for this species. PMID- 25118807 TI - Profile of microRNAs associated with aging in rat liver. AB - Recent studies suggest that small non-coding microRNAs (miRNAs or miRs) play an important role in the regulation of genes involved in various cellular and developmental processes. However, the expression of miRNAs during the aging process remains largely unknown. The aim of the present study was to analyze miRNA expression profiles in rat livers during the aging process. The livers of male Wistar rats at different stages of development (fetal, aged 3 days, and 1, 2, 4, 8 and 36 weeks of age) were used. Total RNA was extracted from the livers. We analyzed the expression levels of 679 rat miRNA probes. In addition, immunohistochemical staining for proliferating cell nuclear antigen (PCNA) was performed. Several up- and downregulated miRNAs were identified in the rat livers at 7 different fetal developmental stages and at 36 weeks of age. We observed the upregulation of miR-29a, miR-29c, miR-195 and miR-497, whereas miR-301a, miR-148b 3p, miR-7a, miR-93, miR-106b, miR-185, miR-450a, miR-539 and miR-301b were downregulated in the aging rat livers. The number of PCNA-positive hepatocytes was decreased with age. In conclusion, our findings suggest that these up- and downregulated miRNAs play an important role in aging by regulating cell cycles that are involved in liver senescence. Further investigation is required to reveal additional target genes of the miRNAs expressed in the liver and the roles of miRNAs in the developmental process of aging in the liver. PMID- 25118808 TI - Unusual cyclic terpenoids with terminal pendant prenyl moieties: from occurrence to synthesis. AB - The paper reviews the known examples of cyclic terpenoids produced from open chain polyenic precursors by an "unusual" biosynthetic pathway, involving selective electrophilic attack on an internal double bond followed by cyclization. The resulting compounds possess cyclic backbones with pendant terminal prenyl groups. Synthetic approaches applied for the synthesis of such specifically functionalized compounds are also discussed, as well as biological activity of reported representatives. PMID- 25118809 TI - Protuberant fibro-osseous lesions of the temporal bone: two additional case reports. AB - The most commonly encountered fibro-osseous lesions of the skull bone are fibrous dysplasia and ossifying fibroma. Two cases of a unique "protuberant fibro-osseous lesion of the temporal bone" were first described by Selesnick and colleagues in 1999, and 2 further cases were reported in 2010 under the name "Bullough lesion". We recently found 2 new cases of this rare entity. Two Korean female patients aged 70 and 54 years presented with slow growing postauricular masses without pain or tenderness for 6 and 7 years, respectively. Computed tomography revealed a 2.9 cm calcified mass in the temporal bone of the first patient, and a 5.5 cm enhancing mass with internal cartilaginous matrix in the temporal bone of the second patient. Intramedullary or intracranial extension was not found in either case, and en bloc removals were performed. Microscopically, multiple round to oval osseous islands were scattered throughout the bland fibrous stroma in both cases. The osseous islands varied in size and were lamellar or woven, without osteoblastic rimming, and surrounded by fibroblastic bands. Neither patient has shown evidence of postoperative recurrence for 18 months. The location, histology, and clinical course of these 2 cases were identical to the 4 cases previously reported, although age and sex varied. The lesions were tested for the R201H mutation in the GNAS gene, which is present in fibrous dysplasia. No mutations were found, suggesting a different genetic background for these lesions. PMID- 25118806 TI - The potential of transcription factor-based genetic engineering in improving crop tolerance to drought. AB - Drought is one of the major constraints in crop production and has an effect on a global scale. In order to improve crop production, it is necessary to understand how plants respond to stress. A good understanding of regulatory mechanisms involved in plant responses during drought will enable researchers to explore and manipulate key regulatory points in order to enhance stress tolerance in crops. Transcription factors (TFs) have played an important role in crop improvement from the dawn of agriculture. TFs are therefore good candidates for genetic engineering to improve crop tolerance to drought because of their role as master regulators of clusters of genes. Many families of TFs, such as CCAAT, homeodomain, bHLH, NAC, AP2/ERF, bZIP, and WRKY have members that may have the potential to be tools for improving crop tolerance to drought. In this review, the roles of TFs as tools to improve drought tolerance in crops are discussed. The review also focuses on current strategies in the use of TFs, with emphasis on several major TF families in improving drought tolerance of major crops. Finally, many promising transgenic lines that may have improved drought responses have been poorly characterized and consequently their usefulness in the field is uncertain. New advances in high-throughput phenotyping, both greenhouse and field based, should facilitate improved phenomics of transgenic lines. Systems biology approaches should then define the underlying changes that result in higher yields under water stress conditions. These new technologies should help show whether manipulating TFs can have effects on yield under field conditions. PMID- 25118810 TI - Activating BRAF V600E mutation in aggressive pediatric Langerhans cell histiocytosis: demonstration by allele-specific PCR/direct sequencing and immunohistochemistry. AB - Langerhans cell histiocytosis (LCH) is a rare neoplastic disease originating from cells characterized by antigen-presenting Langerhans cell phenotype. The clinical spectrum of LCH is highly variable including localized and disseminated forms mostly occurring in children. Recently, about 60% of LCHs were reported to carry the activating BRAF mutation V600E. In our retrospective study, we evaluated the occurrence and prognostic impact of the V600E mutation in formaldehyde-fixed, paraffin-embedded samples from 15 pediatric LCH cases treated at our institution. Allele-specific polymerase chain reaction (PCR) and direct sequencing were used to demonstrate the presence of V600E mutation, and immunohistochemistry (IHC) using the mutant protein-specific VE1 antibody clone was performed to confirm mutant BRAF protein expression. Eight of 15 (53.3%) cases proved to be BRAF mutants by any of the methods applied, with a single case showing a discrepancy (PCR negative/IHC positive). Four of the BRAF-mutant cases (50.0%) showed refractory disease and progressed to death within 43 months, whereas the remaining mutant cases were stable and responded well to therapy. Wild-type BRAF cases (7/15, 46.6%) with generally comparable initial presentation were all treated successfully. In conclusion, activating V600E BRAF mutation can be frequently demonstrated in pediatric LCH by both allele-specific PCR and IHC. Unfavorable risk cases potentially also responding to BRAF-inhibitory therapy can be identified by mutation testing using archival formaldehyde-fixed, paraffin embedded tumor samples. PMID- 25118811 TI - Uterine polyps with features overlapping with those of Mullerian adenosarcoma: a clinicopathologic analysis of 29 cases emphasizing their likely benign nature. AB - Mullerian adenosarcoma (MA) is a mixed Mullerian neoplasm composed of malignant stroma and benign epithelium. Endometrial and endocervical polyps are common entities in surgical pathology practice and most can be readily distinguished from MA; however, some have overlapping features, causing diagnostic confusion. In this study, we examined uterine polyps falling short of the diagnosis of MA quantitatively, qualitatively, or both. Our aims were to (1) characterize formally the morphologic features of atypical uterine polyps and (2) determine clinical outcome. Cases were evaluated for morphologic features of MA (phyllodes like architecture, intraglandular polypoid projections, altered periglandular stroma, and stromal cytologic atypia), and the maximum number of mitoses per 10 high-power fields. The percentage involvement within a polyp by any atypical feature was estimated. The most common change was abnormal architecture, although periglandular stromal abnormalities and increased mitoses were also frequent findings. Stromal cytologic atypia was rare and when present was focal and mild. Histologic follow-up was performed in 24/29 (86%). Two patients had uterine polyps with unusual features similar to those noted on the initial biopsy. The remainder showed either polyp without unusual features or no residual polyp. Clinical follow-up information was available for 28/29 (97%). Twenty-seven of 28 were alive without evidence of disease, whereas 1 patient had died of pancreatic adenocarcinoma. We have shown that uterine polyps with features overlapping with those of MA have a benign clinical course, even with conservative management, as no cases showed progression or malignant transformation. PMID- 25118812 TI - Distinguishing nested variants of urothelial carcinoma from benign mimickers by TERT promoter mutation. AB - Nested variant of urothelial carcinoma (NVUC) is an uncommon variant with minimally atypical cytology, which may overlap with benign urothelial lesions such as von Brunn nests, cystitis cystica, cystitis glandularis, and nephrogenic adenoma. Because of the tumor's deceptively bland appearance, these cancers can potentially be misdiagnosed as benign lesions, leading in some cases to a significant delay in correct diagnosis and appropriate treatment. Prior studies suggest that Ki67 and p53 are useful markers in distinguishing NVUC from benign lesions. However, the overlap in the rates of immunoreactivity has prevented pathologists from using these markers as reliable adjunct markers in differentiating NVUC from mimickers. In addition, large nested variant urothelial carcinoma (LNVUC), a relatively new entity, shares features of both the NVUC and papillary urothelial carcinomas with an inverted growth pattern. They also mimic benign lesions, such as proliferation of von Brunn nests and inverted urothelial papilloma. With the recent demonstration of a strong association of TERT promoter mutations and urothelial carcinoma, we hypothesized that TERT promoter mutations would be a useful marker to distinguish NVUC and LNVUC from other benign urothelial lesions. We have therefore sequenced the TERT promoter region of 20 cases of NVUC, 10 cases of LNVUC, 5 cases of von Brunn nests, 3 cases of cystitis cystica, 3 cases of cystitis glandularis, and 3 cases of nephrogenic adenoma. We found that 17 of 20 cases of NVUC and 8 of 10 cases of LNVUC had TERT promoter mutation: C228T; no mutation was found in any of the benign mimickers (0/14). This result strongly suggests that TERT promoter mutation is a useful adjunct biomarker to distinguish NVUC and LNVUC from benign mimickers. PMID- 25118813 TI - Gastrointestinal tract-derived pulse granulomata: clues to an underrecognized pseudotumor. AB - Pulse granulomata (PG) in the lung and oral pathology literature are presumed due to food (pulse) introduced by mucosal injury. Herein, we report the largest series of PG in the gastrointestinal tract (GIT): 22 resections were prospectively collected from 17 patients (8 men, range=28 to 85 y). All patients had a history of intestinal injury/disease: diverticulitis, fistula, adenocarcinoma, perforation, ulcerative colitis, appendicitis, anastomotic site leak, and/or stent leak. Nine of 22 specimens were designated "masses"; most of these were clinically concerning for neoplasia. Sites of involvement included the small and large intestine, appendix, liver, gallbladder, mesentery, omentum, peritoneum, cervix, ovary, and skin. PG were typically nodular (21/22) and multifocal (15/22); most involved the external surface of the bowel (20/22), and they ranged in size from 1.5 to 100 mm. Histologically, they contained variable amounts of hyaline ribbons and rings, inflammation, foreign body giant cells, calcifications, and food; larger lesions displayed circumferential stellate fibrosis (12/22). We describe 3 morphologic variants: hyaline predominant (mimicking amyloid), cellular predominant (mimicking spindle cell neoplasms), and sclerosing mesenteritis-like. All patients are alive and well at the time of follow-up. Histologically processed legumes showed similar structures as those identified in PG, providing support for an entrapped food origin. In summary, we detail important clinicopathologic clues, describe the PG morphologic spectrum, and demonstrate how to distinguish PG from their mimics. Although PG can present as clinically concerning masses, we conclude that they are pseudotumors arising secondary to entrapped food introduced through mucosal trauma, similar to their lung and oral counterparts. PMID- 25118814 TI - Annexin A10 expression in microsatellite-unstable colorectal cancers: is it specific to sporadic tumors? PMID- 25118815 TI - Lobular panniculitic infiltrates with overlapping histopathologic features of lupus panniculitis (lupus profundus) and subcutaneous T-cell lymphoma: a conceptual and practical dilemma. AB - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is characterized by panniculitic infiltrates that may be difficult to distinguish from inflammatory disorders, particularly lupus erythematosus profundus (LEP). We report on 11 patients (M:F=5:6; median age: 49 y; range: 20 to 75 y) presenting with lobular panniculitic infiltrates showing histopathologic features of both SPTCL and LEP in different parts of the same biopsy specimen. The areas showing aspects of SPTCL revealed dense infiltrates of small and medium-sized, atypical alpha/beta T cytotoxic lymphocytes with focal rimming of the adipocytes and high proliferation. In other areas the infiltrate was composed of nodules of B lymphocytes arranged characteristically at the periphery of the fat lobules and in the septa and showing a low proliferation rate. CD123-positive plasmocytoid dendritic cells arranged in small clusters could be observed in 3 cases. Our observation raises an important question concerning the relationship between SPTCL and LEP. A simple chance overlap of 2 unrelated pathologies seems unlikely, as we could observe these unusual features in 11 cases, much more than mere chance would justify. Three other hypotheses may explain the features observed in our patients: (1) these are examples of SPTCL with focal histologic features mimicking those of LEP; (2) these are examples of LEP with focal atypical histologic features mimicking those of SPTCL; (3) SPTCL and LEP may represent 2 ends of a spectrum, a hypothesis that may be supported by the frequent association of the 2 diseases. PMID- 25118817 TI - Light sheet fluorescence microscopy (LSFM): past, present and future. AB - Light sheet fluorescence microscopy (LSFM) has emerged as an important imaging modality to follow biology in live 3D samples over time with reduced phototoxicity and photobleaching. In particular, LSFM has been instrumental in revealing the detail of early embryonic development of Zebrafish, Drosophila, and C. elegans. Open access projects, DIY-SPIM, OpenSPIM, and OpenSPIN, now allow LSFM to be set-up easily and at low cost. The aim of this paper is to facilitate the set-up and use of LSFM by reviewing and comparing open access projects, image processing tools and future challenges. PMID- 25118816 TI - Intracellular TCR-signaling pathway: novel markers for lymphoma diagnosis and potential therapeutic targets. AB - Despite the immunologic functions of T-cell receptor signaling molecules being extensively investigated, their potential as immunohistochemical markers has been poorly explored. With this background, we evaluated the expression of 5 intracellular proteins-GADS, DOK2, SKAP55, ITK, and PKCalpha-involved in T-cell receptor signaling in normal and neoplastic hematologic tissue samples, using antibodies raised against fixation-resistant epitopes of the 5 molecules. All 5 antibodies were associated with normal T-cell differentiation. GADS, DOK2, SKAP55, and ITK turned out to be T-cell lineage-specific markers in the setting of lymphoid and myeloid precursor neoplasms but showed differential expression in peripheral T-cell lymphoma (PTCL) subtypes, being detected in PTCL/not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma but negative in anaplastic large cell lymphoma (ALCL). Peripheral B-cell lymphomas were consistently negative for ITK, with occasional cases showing expression of DOK2 and SKAP55, and a proportion (47%) of hairy cell leukemias were GADS. Notably, PKCalpha highlighted a defective antigen in both PTCL/NOS (6%) and angioimmunoblastic T cell lymphoma (10%), mostly negative in ALCL, and was aberrantly expressed in classical Hodgkin lymphoma (65%), Burkitt lymphoma (48%), and plasma cell myeloma (48%). In conclusion, all five molecules evaluated play a role in T-cell differentiation in normal and neoplastic tissues. They can be applied confidently to routine sections contributing primarily to assignment of T-lineage differentiation in the setting of hematopoietic precursor neoplasms (GADS/DOK2/SKAP55/ITK) and for the differential diagnosis between ALCL and PTCL/NOS (GADS/DOK2/SKAP55/ITK) or classical Hodgkin lymphoma (PKCalpha). Finally, association with specific tumor subtypes may have therapeutic potential. PMID- 25118818 TI - Controlled drug release from the aggregation-disaggregation behavior of pH responsive microgels. AB - In this submission, two independent sets of microgels were synthesized that exhibit pH responsivity over different solution pH ranges. The microgels were synthesized by copolymerizing two different comonomers with poly(N isopropylacrylamide) (pNIPAm). The microgels copolymerized with acrylic acid exhibit a negative charge above pH 4.25, while the microgels copolymerized with N [3-(dimethylamino)propyl]methacrylamide exhibit a positive charge below pH 8.4; these microgels are neutral outside of these pH ranges. We show that aggregates form when the two independent sets of microgels are exposed to one another in a solution that renders them both charged. Furthermore, in solutions of pH outside of this range, the microgels disaggregate because one of the microgels becomes neutralized. This behavior was exploited to load (aggregation) and release (disaggregation) a small-molecule model drug, methylene blue. This aggregate based system is one example of how pNIPAm-based microgels can be used for controlled/triggered drug delivery, which can have implications for therapeutics. PMID- 25118820 TI - Crystal structure and luminescence property of a novel blue-emitting Cs2xCa2xGd2(1-x)(PO4)2:Eu(2+) (x = 0.36) phosphor. AB - A novel blue-emitting double-phosphate phosphor Cs0.72Ca0.72Gd1.28(PO4)2:Eu(2+) was synthesized by the sol-gel method, and the structure and luminescence properties were investigated in detail. The crystal structure and chemical composition of Cs0.72Ca0.72Gd1.28(PO4)2 matrix was analyzed and determined based on Rietveld refinements and phase and chemical composition analysis. The composition-optimized Cs0.72Ca0.72Gd1.28(PO4)2:Eu(2+) exhibited strong blue light, peaking at 462 nm upon excitation at 365 nm with the CIE coordinates of (0.139, 0.091). The quenching concentration of Eu(2+) in the Cs0.72Ca0.72Gd1.28(PO4)2 phase was about 0.01 and attributed to the dipole quadrupole interaction. The thermally stable luminescence properties, fluorescence decay curves and diffuse reflectance spectra of Cs0.72Ca0.72Gd1.28(PO4)2:Eu(2+) phosphors are also discussed, all of which indicate that the Cs0.72Ca0.72Gd1.28(PO4)2:Eu(2+) phosphor is a promising phosphor for application in white-light UV LEDs. PMID- 25118819 TI - Quantitative comparison and metabolite profiling of saponins in different parts of the root of Panax notoginseng. AB - Although both rhizome and root of Panax notoginseng are officially utilized as notoginseng in "Chinese Pharmacopoeia", individual parts of the root were differently used in practice. To provide chemical evidence for the differentiated usage, quantitative comparison and metabolite profiling of different portions derived from the whole root, as well as commercial samples, were carried out, showing an overall higher content of saponins in rhizome, followed by main root, branch root, and fibrous root. Ginsenoside Rb2 was proposed as a potential marker with a content of 0.5 mg/g as a threshold value for differentiating rhizome from other parts. Multivariate analysis of the metabolite profile further suggested 32 saponins as potential markers for the discrimination of different parts of notoginseng. Collectively, the study provided comprehensive chemical evidence for the distinct usage of different parts of notoginseng and, hence, is of great importance for the rational application and exploitation of individual parts of notoginseng. PMID- 25118821 TI - Oxidative dehydrogenation of ethane on dynamically rearranging supported chloride catalysts. AB - Ethane is oxidatively dehydrogenated with a selectivity up to 95% on catalysts comprising a mixed molten alkali chloride supported on a mildly redox-active Dy2O3-doped MgO. The reactive oxyanionic OCl(-) species acting as active sites are catalytically formed by oxidation of Cl(-) at the MgO surface. Under reaction conditions this site is regenerated by O2, dissolving first in the alkali chloride melt, and in the second step dissociating and replenishing the oxygen vacancies on MgO. The oxyanion reactively dehydrogenates ethane at the melt-gas phase interface with nearly ideal selectivity. Thus, the reaction is concluded to proceed via two coupled steps following a Mars-van-Krevelen-mechanism at the solid-liquid and gas-liquid interface. The dissociation of O2 and/or the oxidation of Cl(-) at the melt-solid interface is concluded to have the lowest forward rate constants. The compositions of the oxide core and the molten chloride shell control the catalytic activity via the redox potential of the metal oxide and of the OCl(-). Traces of water may be present in the molten chloride under reaction conditions, but the specific impact of this water is not obvious at present. The spatial separation of oxygen and ethane activation sites and the dynamic rearrangement of the surface anions and cations, preventing the exposure of coordinatively unsaturated cations, are concluded to be the origin of the surprisingly high olefin selectivity. PMID- 25118823 TI - Narrative review of the barriers and facilitators to chlamydia testing in general practice. AB - As the cornerstone of Australian primary health care, general practice is a setting well suited for regular chlamydia testing but testing rates remain low. This review examines the barriers and facilitators to chlamydia testing in general practice. Six databases--Medline, PubMed, Meditext, PsycInfo, Scopus and Web of Science--were used to identify peer-reviewed publications that addressed barriers and facilitators to chlamydia testing in general practice using the following terms: 'chlamydia test*', 'STI test*' 'general practice', 'primary care', 'family medicine', 'barriers', 'facilitators' and 'enablers' from 1997 until November 2013. Data about the study design and key findings were extracted from the publications. A framework method was used to manage the data and organise publications into three categories -patient, general practitioner, and general practice. Key findings were then classified as a barrier or facilitator. Sixty-nine publications were included, with 41 quantitative studies, 17 qualitative studies, and 11 using mixed methods. Common barriers identified in all three groups included a lack of knowledge, awareness or training, demands on time and workload, and the social context of testing. Facilitators included the normalisation of testing, the use of nurses and other practice staff, education and incentives. Numerous barriers and facilitators to chlamydia testing in general practice have been identified. While the barriers are well studied, many of the facilitators are not as well researched, and highlight areas for further study. PMID- 25118822 TI - Generation of Ugt1-deficient murine liver cell lines using TALEN technology. AB - The Crigler-Najjar Syndrome Type I (CNSI) is a rare genetic disorder caused by mutations in the Ugt1a1 gene. It is characterized by unconjugated hyperbilirubinemia that may result in severe neurologic damage and death if untreated. To date, liver transplantation is the only curative treatment. With the aim of generating mutant cell lines of the Ugt1 gene, we utilized the TALEN technology to introduce site-specific mutations in Ugt1 exon 4. We report a fast and efficient method to perform gene knockout in tissue culture cells, based on the use of TALEN pairs targeting restriction enzyme (RE) sites in the region of interest. This strategy overcame the presence of allele-specific single nucleotide polymorphisms (SNPs) and pseudogenes, conditions that limit INDELs' detection by Surveyor. We obtained liver-derived murine N-Muli cell clones having INDELs with efficiency close to 40%, depending on the TALEN pair and RE target site. Sequencing of the target locus and WB analysis of the isolated cell clones showed a high proportion of biallelic mutations in cells treated with the most efficient TALEN pair. Ugt glucuronidation activity was reduced basal levels in the biallelic mutant clones. These mutant liver-derived cell lines could be a very useful tool to study biochemical aspects of Ugt1 enzyme activity in a more natural context, such as substrate specificity, requirement of specific co factors, the study of inhibitors and other pharmacological aspects, and to correlate enzyme activity to the presence of specific mutations in the gene, by adding back to the mutant cell clones specific variants of the Ugt1 gene. In addition, since genome editing has recently emerged as a potential therapeutic approach to cure genetic diseases, the definition of the most efficient TALEN pair could be an important step towards setting up a platform to perform genome editing in CNSI. PMID- 25118824 TI - Influence of functional groups on organic aerosol cloud condensation nucleus activity. AB - Organic aerosols in the atmosphere are composed of a wide variety of species, reflecting the multitude of sources and growth processes of these particles. Especially challenging is predicting how these particles act as cloud condensation nuclei (CCN). Previous studies have characterized the CCN efficiency for organic compounds in terms of a hygroscopicity parameter, kappa. Here we extend these studies by systematically testing the influence of the number and location of molecular functional groups on the hygroscopicity of organic aerosols. Organic compounds synthesized via gas-phase and liquid-phase reactions were characterized by high-performance liquid chromatography coupled with scanning flow CCN analysis and thermal desorption particle beam mass spectrometry. These experiments quantified changes in kappa with the addition of one or more functional groups to otherwise similar molecules. The increase in kappa per group decreased in the following order: hydroxyl ? carboxyl > hydroperoxide > nitrate ? methylene (where nitrate and methylene produced negative effects, and hydroperoxide and nitrate groups produced the smallest absolute effects). Our results contribute to a mechanistic understanding of chemical aging and will help guide input and parametrization choices in models relying on simplified treatments such as the atomic oxygen:carbon ratio to predict the evolution of organic aerosol hygroscopicity. PMID- 25118825 TI - Vapor-wall deposition in chambers: theoretical considerations. AB - In order to constrain the effects of vapor-wall deposition on measured secondary organic aerosol (SOA) yields in laboratory chambers, researchers recently varied the seed aerosol surface area in toluene oxidation and observed a clear increase in the SOA yield with increasing seed surface area (Zhang, X.; et al. Proc. Natl. Acad. Sci. U.S.A. 2014, 111, 5802). Using a coupled vapor-particle dynamics model, we examine the extent to which this increase is the result of vapor-wall deposition versus kinetic limitations arising from imperfect accommodation of organic species into the particle phase. We show that a seed surface area dependence of the SOA yield is present only when condensation of vapors onto particles is kinetically limited. The existence of kinetic limitation can be predicted by comparing the characteristic time scales of gas-phase reaction, vapor-wall deposition, and gas-particle equilibration. The gas-particle equilibration time scale depends on the gas-particle accommodation coefficient alphap. Regardless of the extent of kinetic limitation, vapor-wall deposition depresses the SOA yield from that in its absence since vapor molecules that might otherwise condense on particles deposit on the walls. To accurately extrapolate chamber-derived yields to atmospheric conditions, both vapor-wall deposition and kinetic limitations must be taken into account. PMID- 25118827 TI - Evaluation of visual acuity, macular status, and subfoveal choroidal thickness changes after cataract surgery in eyes with diabetic retinopathy. AB - PURPOSE: Progression of diabetic macular edema has been reported as a common cause of poor visual acuity recovery after cataract surgery in patients with diabetes. Despite being responsible for the blood supply to the outer retina, the role of the choroidal layer in the pathogenesis of diabetic retinopathy (DR) is not yet understood. Our objective is to characterize macular and subfoveal choroidal thickness changes after cataract surgery in eyes with DR. METHODS: Thirty-five eyes with clinically significant cataract of patients with DR were divided into three groups based on clinical and optical coherence tomography findings: patients with DR without macular edema, patients with DR and macular thickening detected on optical coherence tomography, and finally patients with clinically significant macular edema. All cases were submitted to ophthalmologic examination and spectral domain optical coherence tomography 1 week before cataract surgery and repeated 1 month after surgery. Patients with preoperative clinically significant macular edema were treated with intravitreal bevacizumab at the time of surgery. RESULTS: All groups showed a significant increase in visual acuity 1 month after surgery (P < 0.001). Mean foveal thickness increased significantly in all groups, including controls (P = 0.013), except in patients who were simultaneously treated with intravitreal bevacizumab (P = 0.933). An increase of maximum macular thickness of at least 11% was found in 25.7% of the DR eyes, but no such increase occurred in the control eyes. No significant change was verified for subfoveal choroidal thickness in any of the studied groups. CONCLUSION: Surgical inflammation associated with cataract surgery caused a significant increase of macular thickness in control and DR eyes that were not treated with intravitreous bevacizumab. Such macular changes were not accompanied by subfoveal choroidal thickness changes in any of the study groups, suggesting that the changes in macular thickness associated with the surgery are not related to changes in choroidal thickness and that there is no relation between inner blood-retinal barrier status and diabetic choroidal angiopathy. PMID- 25118826 TI - Polysialylated N-glycans identified in human serum through combined developments in sample preparation, separations, and electrospray ionization-mass spectrometry. AB - The N-glycan diversity of human serum glycoproteins, i.e., the human blood serum N-glycome, is both complex and constrained by the range of glycan structures potentially synthesizable by human glycosylation enzymes. The known glycome, however, has been further limited by methods of sample preparation, available analytical platforms, e.g., based upon electrospray ionization-mass spectrometry (ESI-MS), and software tools for data analysis. In this report several improvements have been implemented in sample preparation and analysis to extend ESI-MS glycan characterization and to include polysialylated N-glycans. Sample preparation improvements included acidified, microwave-accelerated, PNGase F N glycan release to promote lactonization, and sodium borohydride reduction, that were both optimized to improve quantitative yields and conserve the number of glycoforms detected. Two-stage desalting (during solid phase extraction and on the analytical column) increased sensitivity by reducing analyte signal division between multiple reducing-end-forms or cation adducts. Online separations were improved by using extended length graphitized carbon columns and adding TFA as an acid modifier to a formic acid/reversed phase gradient, providing additional resolving power and significantly improved desorption of both large and heavily sialylated glycans. To improve MS sensitivity and provide gentler ionization conditions at the source-MS interface, subambient pressure ionization with nanoelectrospray (SPIN) was utilized. When these improved methods are combined together with the Glycomics Quintavariate Informed Quantification (GlyQ-IQ) recently described (Kronewitter et al. Anal. Chem. 2014, 86, 6268-6276), we are able to significantly extend glycan detection sensitivity and provide expanded glycan coverage. We demonstrated the application of these advances in the context of the human serum glycome, and for which our initial observations included the detection of a new class of heavily sialylated N-glycans, including polysialylated N-glycans. PMID- 25118828 TI - Fractional anisotropy in corpus callosum is associated with facilitation of motor representation during ipsilateral hand movements. AB - BACKGROUND: Coactivation of primary motor cortex ipsilateral to a unilateral movement (M1(ipsilateral)) has been observed, and the magnitude of activation is influenced by the contracting muscles. It has been suggested that the microstructural integrity of the callosal motor fibers (CMFs) connecting M1 regions may reflect the observed response. However, the association between the structural connectivity of CMFs and functional changes in M1(ipsilateral) remains unclear. The purpose of this study was to investigate the relationship between functional changes within M1(ipsilateral) during unilateral arm or leg movements and the microstructure of the CMFs connecting both homotopic representations (arm or leg). METHODS: Transcranial magnetic stimulation was used to assess changes in motor evoked potentials (MEP) in an arm muscle during unilateral movements compared to rest in fifteen healthy adults. Functional magnetic resonance imaging was then used to identify regions of M1 associated with either arm or leg movements. Diffusion-weighted imaging data was acquired to generate CMFs for arm and leg areas using the areas of activation from the functional imaging as seed masks. Individual values of regional fractional anisotropy (FA) of arm and leg CMFs was then calculated by examining the overlap between CMFs and a standard atlas of corpus callosum. RESULTS: The change in the MEP was significantly larger in the arm movement compared to the leg movement. Additionally, regression analysis revealed that FA in the arm CMFs was positively correlated with the change in MEP during arm movement, whereas a negative correlation was observed during the leg movement. However, there was no significant relationship between FA in the leg CMF and the change in MEP during the movements. CONCLUSIONS: These findings suggest that individual differences in interhemispheric structural connectivity may be used to explain a homologous muscle-dominant effect within M1(ipsilateral) hand representation during unilateral movement with topographical specificity. PMID- 25118830 TI - Room-temperature near-infrared high-Q perovskite whispering-gallery planar nanolasers. AB - Near-infrared (NIR) solid-state micro/nanolasers are important building blocks for true integration of optoelectronic circuitry. Although significant progress has been made in III-V nanowire lasers with achieving NIR lasing at room temperature, challenges remain including low quantum efficiencies and high Auger losses. Importantly, the obstacles toward integrating one-dimensional nanowires on the planar ubiquitous Si platform need to be effectively tackled. Here we demonstrate a new family of planar room-temperature NIR nanolasers based on organic-inorganic perovskite CH3NH3PbI(3-a)X(a) (X = I, Br, Cl) nanoplatelets. Their large exciton binding energies, long diffusion lengths, and naturally formed high-quality planar whispering-gallery mode cavities ensure adequate gain and efficient optical feedback for low-threshold optically pumped in-plane lasing. We show that these remarkable wavelength tunable whispering-gallery nanolasers can be easily integrated onto conductive platforms (Si, Au, indium tin oxide, and so forth). Our findings open up a new class of wavelength tunable planar nanomaterials potentially suitable for on-chip integration. PMID- 25118829 TI - Cachexia: a problem of energetic inefficiency. AB - An alteration of energy balance is the immediate cause of the so-called cachexia. Although alterations of energy intake are often associated with cachexia, it has lately became clear that an increased energy expenditure is the main cause of wasting associated with different types of pathological conditions, such as cancer, infections or chronic heart failure among others. Different types of molecular mechanisms contribute to energy expenditure and, therefore, involuntary body weight loss; among them, adenosine triphosphate (ATP) consumption by sarcoplasmic reticulum Ca(2+) pumps could represent a key mechanism. In other cases, an increase in energy inefficiency will further contribute to energy imbalance. PMID- 25118831 TI - High-level expression and characterization of bioactive human truncated variant of hepatocyte growth factor in Escherichia coli. AB - Hepatocyte growth factor (HGF) is an effective anti-fibrotic factor because of its bioactivity in inhibiting fibrosis-related proteins in the development of hepatic fibrosis. However, high-level production of bioactive mature form HGF is difficult because of its complex structure. Here, we report a non-fusion protein expression system to obtain truncated variant of N-terminal hairpin and first kringle domains of HGF (tvNK1) in Escherichia coli to determine its anti-fibrotic effects on hepatic stellate cells (HSCs). Under the selected conditions of cultivation and isopropyl-beta-D-1-thiogalactopyranoside induction, the expression level of tvNK1 accounted for approximately 65 % of the total cellular protein and 50 % of fusion protein in the supernatant of whole cell lysates. The recombinant protein could be purified in one step with Ni(2+)-affinity chromatograph. Finally, about 65 mg recombinant tvNK1 was obtained from 1 l fermentation culture with no <95 % purity. In vitro, the final purified tvNK1 was shown to inhibit the proliferation of HSCs and decrease the mRNA and protein expression levels of fibrosis-related COL1A1 and alpha-smooth muscle actin genes. PMID- 25118832 TI - Celastrus paniculatus Willd. mitigates t-BHP induced oxidative and apoptotic damage in C2C12 murine muscle cells. AB - Identification, exploration and scientific validation of antioxidant rich herbal extracts to mitigate the radical induced cell damage provide new insights in the field of ayurvedic research/therapies. In the present study, we evaluated the anti-oxidant and anti-apoptotic potential of Celastrus paniculatus seed extract (CPSE) against tertiary butyl hydroperoxide (t-BHP) induced mice muscle cell damage. The extract at a dose of 50 ug/ml protected the cells up to 70 % as evidenced by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell survival assay and also prevented LDH leakage against t-BHP induced cytotoxicity. CPSE showed potential antioxidant activity by restoring mitochondrial membrane potential and inhibited reactive oxygen species generation and lipid peroxidation. CPSE pretreatment also regulated the antioxidant markers such as superoxide dismutase and catalase enzymes content and proteins expression. Further CPSE showed anti-apoptotic effects by regulating cytochrome-C and heat shock protein-70 expression and also showed 43 % muscle cell DNA damage inhibitory activity against t-BHP challenge as observed by single cell gel electrophoresis assay. Overall the extract inhibits the muscle cell damage, thus explaining the possible anti-oxidant/anti-apoptotic defense status of the C. paniculatus seed extract. PMID- 25118833 TI - Vitamin A concentration in human milk and its relationship with liver reserve formation and compliance with the recommended daily intake of vitamin A in pre term and term infants in exclusive breastfeeding. AB - PURPOSE: To evaluate vitamin A concentration in mature breast milk of nursing mothers aiming to meet the daily needs and the formation of liver reserve in pre term (PT) and term infants (T) in comparison with the recommended intake for this nutrient in this group. METHODS: We analyzed the retinol concentration in the milk of 120 nursing mothers (40 of PT infants and 80 of T infants) by collecting 10 mL of mature breast milk, held by a hand spray of one of the breasts 2 h after the last feeding in the morning. The cutoff points adopted for identification of vitamin A deficiency (VAD) and the liver reserve were <1.05 and >2.3 MUmol/L, respectively. RESULTS: The concentrations of retinol in the human milk of T infants were superior to concentrations in the milk of PT infants (1.87 + 0.81 > 1.38 + 0.67 MUmol/L, p < 0.0001). They were higher in T compared to PT (352.64 + 152.72 > 217.65 + 105.65 MUg, p < 0.0001), but both were below the recommendation. VAD was 20.0 % (T) and 27.5 % (PT). Only 40.0 % (T) and 22.5 % (PT) of the mothers had retinol concentrations in milk above 2.3 mmol/L. CONCLUSION: The milk of the nursing mothers studied did not have enough retinol to meet the daily needs and to form liver reserve in both groups, especially in PT newborns. This finding reinforces the idea that supplementation with massive doses of vitamin A in the immediate postpartum period can be used as a protective device of the infant against VAD. PMID- 25118834 TI - Sequential combination of flavopiridol with Taxol synergistically suppresses human ovarian carcinoma growth. AB - PURPOSE: The purpose is to investigate the effects of the sequential combination treatment of Taxol and flavopiridol on human ovarian carcinoma in vitro and in vivo. METHODS: Cell viabilities were determined using the cell counting kit and by flow cytometry. RT-PCR, TUNEL, and immunoblotting assays were used to detect cellular apoptotic activities following treatments. Tumor growth and microvessel density (MVD) detection of mice bearing SKOV3 cells were studied. RESULTS: Taxol or flavopiridol alone was cytotoxic against SKOV3 cells in vitro with a viability rate of 38.2 +/- 1.3 % for 1 umol/L Taxol and 44.3 +/- 5.9 % for 300 nM flavopiridol. Sequential combination treatment with Taxol and flavopiridol resulted in a viability rate of 9.1 +/- 0.8 %. The apoptotic rate of SKOV3 cells was 15.7 +/- 1.7, 9.4 +/- 0.4 and 51.1 +/- 2.5 % for Taxol, flavopiridol, and combination of Taxol and flavopiridol, respectively. Significant synergisms were observed in SKOV3 cells in vitro, following the sequential combination of Taxol for 24 h followed by flavopiridol for 24 h, which resulted in the most substantial cell death and the highest apoptotic rate. All treatments showed significant suppression of tumor growth at the end point of the in vivo study. All treatments significantly reduce the value of MVD. CONCLUSIONS: Sequential combination treatment with Taxol and flavopiridol exerted synergistic cytotoxic activities against SKOV3 cells in vitro and significantly suppress the tumor growth of mice bearing SKOV3 cells. It should be further explored as a potential clinically useful regimen against ovarian cancer. PMID- 25118835 TI - The expression of GLTSCR2 in cervical intra-epithelial lesion and cancer. AB - BACKGROUND: GLTSCR2 was originally identified as a candidate tumor suppressor in several types of cancers. The present study was to investigate the expression pattern of GLTSCR2 in different cervical lesion tissues, appraise its potential role in cervical cancerogenesis. METHODS: 225 histologically confirmed samples representing a wide range of cervical disease processes were studied in this study using immunohistochemistry (IHC). RESULTS: Compared with normal cervix and low-grade cervical intra-epithelial neoplasia (CIN I), cervical cancer and high grade cervical intra-epithelial neoplasia (CIN II-III) tissues had lower expression scores of IHC staining of GLTSCR2. The positive staining signals of GLTSCR2 in CIN were decreased according to the grades of the intra-epithelial lesions. The IHC scores of GLTSCR2 in cervical cancer tissues were significantly lower than that in adjacent normal tissues. Different from previous report, we also found that GLTSCR2 was expressed in both nucleus and cytoplasm of cervical tissues, and the cytoplasmic expression of GLTSCR2 was observed in almost all tissues. CONCLUSIONS: We demonstrated the GLTSCR2 expression decreased with the rise of the grade of cervical lesions. GLTSCR2 may play an important role in carcinogenesis of cervical cancer. PMID- 25118836 TI - Efficacies and pregnant outcomes of fertility-sparing treatment with medroxyprogesterone acetate for endometrioid adenocarcinoma and complex atypical hyperplasia: our experience and a review of the literature. AB - PURPOSE: We retrospectively analyzed oncologic and reproductive outcomes of fertility-seeking premenopausal women with complex atypical hyperplasia (CAH) or Grade 1 endometrial adenocarcinoma (G1EA) who underwent medical management with high-dose medroxyprogesterone acetate (MPA) therapy. METHODS: Patients were given a dose of 400-600 mg of MPA orally on a daily basis. They had histologically confirmed CAH or G1EA at presumed stage IA and wished to preserve fertility. Endometrial tissue sampling was carried out by dilation and curettage before and after the treatment and the pathologic response to MPA treatment was assessed. RESULTS: A total of 27 premenopausal patients received MPA therapy. The median follow-up time was 39.2 months (3.4-153.8 months). Complete response was achieved in 81.8 % (9/11) of CAH cases and 68.8 % (11/16) of G1EA. Although no recurrences were found in CAH patients, nine G1EA patients (81.8 %) eventually recurred and underwent total hysterectomy. Neither therapeutic death nor irreversible toxicities were observed during the follow-up periods. Five patients (4 CAH and 1 G1EA) became pregnant and had nine live births. CONCLUSION: The high efficacy of fertility-sparing treatment with MPA was shown demonstrated. MPA therapy can be considered acceptable for the purpose of enabling patients to preserve their fertility. However, the rate of recurrence was high in patients with G1EA. Even in responders, close follow-up is required and a total hysterectomy needs to be considered without delay. Patients should be aware of the risks and limitations of this conservative treatment. PMID- 25118837 TI - Glutathione S-transferase M1 modulates allergen-induced NF-kappaB activation in asthmatic airway epithelium. AB - BACKGROUND: Glutathione S-transferase M1 (GSTM1) is a phase II enzyme and regulator of inflammatory signaling in airway epithelial cells. We have found upregulation of neutrophilic airway inflammation in atopic asthmatics expressing GSTM1 gene (GSTM1+) compared to GSTM1null asthmatics. We hypothesized that GSTM1 modulates NF-kappaB activation in bronchial epithelium in atopic asthmatics. We determined regulation of allergen-induced NF-kappaB activation in bronchial epithelium by GSTM1 in human atopic asthmatics in vivo. METHODS: Endobronchial biopsies and bronchoalveolar lavage fluid samples were collected from 13 GSTM1+ and 12 GSTM1null human atopic asthmatics at baseline and 24 h after segmental allergen challenge. A quantitative analysis of NF-kappaB activation in airway epithelium was accomplished using a polyclonal antibody against the phosphorylated p65 component of NF-kappaB. Elastase-positive neutrophils in the bronchial wall were quantified. RESULTS: Postallergen neutrophilia in airway subepithelium and epithelial lining fluid was greater in GSTM1+ compared to GSTM1null asthmatics. Airway eosinophilia was similar in GSTM1+ and GSTM1null asthmatics. Allergen-provoked NF-kappaB induction in bronchial epithelium was significantly greater in GSTM1+ compared to GSTM1null asthmatics. Activation of NF-kappaB activation in airway epithelial cells correlated with interleukin-8 concentrations and absolute neutrophil numbers in bronchoalveolar lavage fluid in GSTM1+ but not GSTM1null asthmatics. CONCLUSIONS: Allergen-induced neutrophilic airway inflammation in GSTM1+ asthmatics is associated with NF-kappaB activation in airway epithelial cells in vivo. These novel data provide a potential mechanism of the genomic link between GSTM1 polymorphism and airway neutrophilia in atopic asthma. PMID- 25118838 TI - Treatment of exertional heat stress developed during low or moderate physical work. AB - PURPOSE: We examined whether treatment for exertional heat stress via ice water immersion (IWI) or natural recovery is affected by the intensity of physical work performed and, thus, the time taken to reach hyperthermia. METHODS: Nine adults (18-45 years; 17.9 +/- 2.8 percent body fat; 57.0 +/- 2.0 mL kg(-1) min(-1) peak oxygen uptake) completed four conditions incorporating either walking or jogging at 40 degrees C (20 % relative humidity) while wearing a non-permeable rain poncho. Upon reaching 39.5 degrees C rectal temperature (Tre), participants recovered either via IWI in 2 degrees C water or via natural recovery (seated in a ~29 degrees C environment) until T re returned to 38 degrees C. RESULTS: Cooling rates were greater in the IWI [Tre: 0.24 degrees C min(-1); esophageal temperature (Tes): 0.24 degrees C min(-1)] than the natural recovery (Tre and Tes: 0.03 degrees C min(-1)) conditions (p < 0.001) with no differences between the two moderate and the two low intensity conditions (p > 0.05). Cooling rates for T re and T es were greater in the 39.0-38.5 degrees C (Tre: 0.19 degrees C min(-1); Tes: 0.31 degrees C min(-1)) compared with the 39.5-39.0 degrees C (Tre: 0.11 degrees C min(-1); Tes: 0.13 degrees C min(-1)) period across conditions (p < 0.05). Similar reductions in heart rate and mean arterial pressure were observed during recovery across conditions (p > 0.05), albeit occurred faster during IWI. Percent change in plasma volume at the end of natural recovery and IWI was 5.96 and 9.58%, respectively (p < 0.001). CONCLUSION: The intensity of physical work performed and, thus, the time taken to reach hyperthermia does not affect the effectiveness of either IWI treatment or natural recovery. Therefore, while the path to hyperthermia may be different for each patient, the path to recovery must always be immediate IWI treatment. PMID- 25118839 TI - Wavelet-based intensity analysis of the mechanomyograph and electromyograph during the H-reflex. AB - PURPOSE: The relationship between mechanomyography (MMG) and electromyography (sEMG) during electrically evoked muscle contraction was examined using the von Tscharner "intensity analysis," which describes the power of a non-stationary signal as a function of both frequency and time. METHOD: Data for 8 college-aged participants (3 males; 5 females) with measurable H-reflexes were analyzed. Recruitment curves for H-reflex (H), M-wave (M) using sEMG, and peak-to-peak MMG (MMGp-p) were elicited through incremental tibial nerve stimulation. The maximum peak-to-peak values for H and M for each sample were summed (HM); and maximum intensity values were measured for MMG, H, and M following the intensity analysis and computation of total intensity (MMGCvT, HCvT, MCvT). HCvT and MCvT were subsequently added together (HMCvT) for comparisons. RESULTS: Correlations of HM:MMGp-p, HM:MMGCvT, HMCvT:MMGCvT, HMCvT:MMGp-p, were low (r = 0.34, 0.33, 0.09, and 0.12, respectively, p < 0.001); and correlations of HM:HMCvT, MMGCvT:MMGp-p, were moderate-to-high (r = 0.69 and 0.97, respectively, p < 0.001). Correlations for individuals ranged from 0.61 to 0.99 across comparisons. The time at which maximal intensities occurred reflected the transition from a predominant H-reflex to the onset of the M-wave and declining lag times were noted with increasing intensity. CONCLUSIONS: The intensity analysis provides insight into the frequency characteristics of the H-reflex and M-wave not seen in traditional analysis of the H-reflex. The intensity analysis may be a useful tool in studying individual variations and changes in the contraction velocities of skeletal muscle. PMID- 25118840 TI - Age difference in efficiency of locomotion and maximal power output in well trained triathletes. AB - PURPOSE: The aim of this study was to examine the influence of age on cycling efficiency and sprint power output in well-trained endurance masters athletes. METHODS: The investigation was conducted on 60 healthy well-trained triathletes separated into six separate groups (n = 10) depending on age: 20-29 years old; 30 39 years old; 40-49 years old; 50-59 years old; 60-69 years old; 70 years old. Each participant attended the laboratory on three separate occasions to perform (1) an incremental cycling test, (2) maximal peak sprint power test, involving three 5-s sprint efforts (3) and a 10-min sub-maximal cycling test for determination of cycling efficiency. RESULTS: Cycling efficiency decreased beyond 50 years (50-59 years compared with 20-29 years: -7.3 +/- 1.8%; p < 0.05) and continued to decrease beyond 60 years (60-69 years compared with 50-59 years: 10.7 +/- 2.4%; p < 0.05), no further decrease was observed after 70 years. A continuous impairment in maximal sprint power output was observed after the age of 50 years leading to an overall decrease of 36% between 20-29 years and >70 years. Significant positive relationships were observed between maximal sprint power output and both cycling efficiency (r(2) = 0.64, p < 0.05) and maximal aerobic power (r(2) = 0.42 and p < 0.05). CONCLUSION: The present data indicates a significant effect of ageing on cycling efficiency and maximal sprint power output after 50 years and a significant relationship was found between these two parameters. PMID- 25118841 TI - Muscle synergies in preparation to a step made with and without obstacle. AB - PURPOSE: To study multi-muscle synergies during preparation in making a step (self-paced level stepping vs. obstacle crossing stepping). METHODS: The uncontrolled manifold hypothesis was used to explore the organization of leg and trunk muscles into groups (M-modes) and co-variation of M-mode involvement (M mode synergies) during stepping tasks. Subjects performed two tasks: (1) making a comfortable step from quiet stance (STCS), (2) stepping over an obstacle of 15% body height from quiet stance, STOS. Electromyographic (EMG) signals of 10 postural muscles were recorded and analyzed. Principal component analysis was used to identify M-modes within the space of integrated indices of muscle activity. Variance in the M-mode space across stepping trials was partitioned into two components, one that did not affect the average value of center of pressure (COP) shift and the other that did. An index (DeltaV) corresponding to the normalized difference between two components of variance was computed. RESULTS: Under the two tasks, strong multi-M-mode synergies stabilizing trajectories of the COP in the anterior-posterior direction were found. Despite the significant differences in the COP shifts and EMG patterns of postural adjustments, the synergies showed only minor differences across the conditions. CONCLUSIONS: These findings demonstrate the robustness of multi-M-mode synergies across different manners of making a step. PMID- 25118842 TI - How standard is standard care? Exploring control group outcomes in behaviour change interventions for young people with type 1 diabetes. AB - OBJECTIVE: Poor descriptions of standard care may compromise interpretation of results in randomised controlled trials (RCTs) of health interventions. We investigated quality of standard care in RCTs of behaviour change interventions for young people with type 1 diabetes and consider implications for evaluating trial outcomes. DESIGN: We conducted systematic searches for articles published between 1999 and 2012. We extracted standard care descriptions and contacted trial authors to complete a checklist of standard care activities. The relationship between standard care quality and outcomes was examined via subgroup meta-analyses and meta-regression. MAIN OUTCOME MEASURES: Standard care descriptions, standard care quality, and relationships between standard care quality with medical and psychological outcomes. RESULTS: We identified 20 RCTs described across 26 articles. Published descriptions of standard care were limited to service-level features. Author responses indicated standard care provision extended beyond published accounts. Subgroup analyses suggested control groups receiving higher standard care quality showed larger improvements in both medical and psychological outcomes, although standard care quality did not predict outcomes significantly. CONCLUSION: The quality of care delivered to control group participants can influence outcomes of RCTs. Inadequate reporting exacerbates this issue by masking variations between trials. We argue for increased clarity in reporting standard care in future trials. PMID- 25118845 TI - Dual-lumen chest port infection rates in patients with head and neck cancer. AB - PURPOSE: The aim of this study was to investigate dual-lumen chest port infection rates in patients with head and neck cancer (HNC) compared to those with other malignancies (non-HNC). MATERIALS AND METHODS: An IRB-approved retrospective study was performed on 1,094 consecutive chest ports placed over a 2-year period. Patients with poor follow-up (n = 53), no oncologic history (n = 13), or single lumen ports (n = 183) were excluded yielding a study population of 845 patients. The electronic medical records were queried for demographic information, data regarding ports and infections, and imaging review. RESULTS: HNC patients experienced more infections (42 vs. 30), an increased infection rate per 1,000 catheter days (0.68 vs. 0.21), and more early infections within 30 days compared to non-HNC patients (10 vs. 6) (p < 0.001, p < 0.001, p = 0.02, respectively). An existing tracheostomy at the time of port placement was associated with infection in the HNC group (p = 0.02) but was not an independent risk factor for infection in the study population overall (p = 0.06). There was a significant difference in age, male gender, and right-sided ports between the HNC and non-HNC groups (p < 0.01, p < 0.001, and p = 0.01), although these were not found to be independent risk factors for infection (p = 0.32, p = 0.76, p = 0.16). CONCLUSION: HNC patients are at increased risk for infection of dual-lumen chest ports placed via a jugular approach compared to patients with other malignancies. Tracheostomy is associated with infection in HNC patients but is not an independent risk factor for infection in the oncologic population as a whole. PMID- 25118843 TI - [Multiple sclerosis : rehabilitation and long-term course]. AB - BACKGROUND: Multiple sclerosis (MS) is a highly complex disabling disease with variable pathology and clinical course. Progressive multisystemic involvement of the central nervous system leads to complex functional disturbances and disabilities. Despite disease-modifying therapies and pharmacological symptomatic treatment, the majority of MS patients develop progressive impairments in functions, activities and quality of life in the long-term. Rehabilitation interventions aim at improving symptoms and functional deficits and reducing the negative impact on activities and social participation. OBJECTIVES: To evaluate the impact and value of rehabilitation interventions in MS. METHODS: Specific literature search in PubMed. RESULTS: Good evidence exists for a positive effect of various rehabilitation interventions and multidisciplinary programs. Long-term prognosis is very variable and depends on various influencing factors. Due to an often unpredictable change of disease activity and the high variability, accurate prediction of long-term prognosis in individual MS cases is still challenging. CONCLUSION: Rehabilitation measures should be considered in an early phase of the disease for maintaining functional abilities and reducing the risk of progression of disabilities. Assignment to specific interventions and setting of rehabilitation depend on disease-specific and personal factors and specific goals. Monosyndromic or oligosyndromic impairments in the early phases of the disease can be approached by targeted monodisciplinary ambulatory interventions, whereas more severe and complex disabilities generally necessitate a more intensive multidisciplinary rehabilitation. PMID- 25118846 TI - Nuclear translocation of lysyl oxidase is promoted by interaction with transcription repressor p66beta. AB - Lysyl oxidase (LOX) is an amine oxidase involved in protein cross-linking of the extracellular matrix. Less well characterized is the role that LOX plays among nuclear proteins, and molecular mechanisms of its transport to the nucleus are currently unknown. Here, we have employed yeast two-hybrid library screening and found that the LOX catalytic domain interacts with the transcription repressor p66beta. This interaction has been confirmed in vitro and has been found to be accomplished through the CR2-containing domain of p66beta. Moreover, co expression of p66beta and LOX in living tumor cells leads to the nuclear accumulation of LOX. Thus, p66beta might be important for the regulation of LOX in the nucleus. PMID- 25118844 TI - [Statement of the German Ophthalmological Society, the Retina Society and the Professional Association of German Ophthalmologists for intravitreal treatment of macular edema in uveitis: Date: 02/07/2014]. PMID- 25118847 TI - Lung transplantation for advanced cystic lung disease due to nonamyloid kappa light chain deposits. AB - RATIONALE: Cystic lung light chain deposition disease (LCDD) is a severe and rare form of nonamyloid kappa light chain deposits localized in the lung, potentially leading to end-stage respiratory insufficiency. OBJECTIVES: To assess the outcome after lung transplantation (LT) in this setting with particular attention to disease recurrence. METHODS: We conducted a retrospective multicenter study of seven patients who underwent LT for cystic lung LCDD in France between September 1992 and June 2012 in five centers. MEASUREMENTS AND MAIN RESULTS: In total, five females and two males (mean age, 39.1 +/- 5.3 yr) underwent one single LT or seven double LT (one retransplantation). Before LT, the patients showed a constant obstructive ventilatory pattern with low carbon monoxide diffusing capacity and resting hypoxemia. Lung computed tomography revealed widespread cysts with occasional micronodulations. No extrapulmonary disease or plasma cell neoplasm was detected. The serum-free kappa/lambda light chain ratio was increased in three cases. The median follow-up after LT was 56 months (range, 1 110 mo). Kaplan-Meier survival was 85.7, 85.7, and 64.3% at 1, 3, and 5 years, respectively. Three patients died from multiorgan failure (n = 1), chronic rejection (n = 1), and breast cancer (n = 1) at 23 days, 56 months, and 96 months, respectively. At the end of follow-up, no patients showed recurrence on imaging or histopathology. CONCLUSIONS: This small case series confirms that cystic lung LCDD is a severe disease limited to the lung, affecting mostly young females. LT appears to be a good therapeutic option allowing for satisfactory long-term survival. We found no evidence of recurrence of the disease after LT. PMID- 25118848 TI - Shopping behavior for ADHD drugs: results of a cohort study in a pharmacy database. AB - OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) medications are subject to abuse, misuse, and diversion. Obtaining ADHD prescriptions from multiple prescribers or filled across multiple pharmacies, known as 'doctor shopping', may reflect such unsanctioned use. We sought to create a definition of shopping behavior that differentiated ADHD medications from medications with low risk of diversion, i.e. asthma medications, and describe the incidence, frequency, and demography of shopping behavior. METHODS: This was a retrospective cohort study in a pharmacy database-LRx-covering 65 % of US retail pharmacies. Subjects had ADHD or asthma medication dispensed between February 2011 and January 2012. We followed subjects for 18 months to assess the number with overlapping dispensings from different prescribers, and the number of prescribers and pharmacies involved in those dispensings. RESULTS: We included 4,402,464 subjects who were dispensed ADHD medications, and 6,128,025 subjects who were dispensed asthma medications. Overlapping prescriptions from two or more prescribers dispensed by three or more pharmacies was four times more frequent in the ADHD cohort than in the asthma cohort. Using this definition, ADHD medication shopping behavior was more common among experienced users than naive users, and was most common in subjects aged 10-39 years. Among subjects who shopped, 57.4 % shopped only once (accounting for 22.4 % of episodes), and 9.2 % shopped six or more times (accounting for 42.0 % of episodes). Shoppers more often received stimulant ADHD drugs than non-stimulants. CONCLUSIONS: Overlapping prescriptions by different prescribers and filled at three or more pharmacies defines ADHD medication shopping. Shopping behavior is most common in adolescents and younger adults. A small proportion of shoppers is responsible for a large number of shopping episodes. PMID- 25118849 TI - Lower urinary tract symptoms in women with diabetes mellitus: a current review. AB - A literature review of the most current publications studying lower urinary tract symptoms (LUTS) and findings in diabetic women was conducted including articles from January 2013 to April 2014. Current reports consistently note that aging and obesity are significantly associated with worsened LUTS in diabetic women. Glucosuria has variable effects on urodynamic parameters and LUTS, but has a significant association with urinary tract infection (UTI) and incontinence at clinically relevant numbers, such as HbA1C values. The presence of severe nocturia in diabetic patients warrants careful surveillance for cardiovascular risks given the significant association with mortality. Diabetics appear to be at higher risk for colonization with the virulent, extended-spectrum, beta-lactamase producing Escherichia coli and Klebsiella species in UTI. Novel therapies in glycemic control and for diabetic bladder dysfunction are undergoing animal model trials with encouraging results. The most promising of these includes stem cell therapy, although a need exists for human studies. PMID- 25118851 TI - Optimizing urology group partnerships: collaboration strategies and compensation best practices. AB - Market forces in health care have created substantial regulatory, legislative, and reimbursement changes that have had a significant impact on urology group practices. To maintain viability, many urology groups have merged into larger integrated entities. Although group operations vary considerably, the majority of groups have struggled with the development of a strong culture, effective decision-making, and consensus-building around shared resources, income, and expense. Creating a sustainable business model requires urology group leaders to allocate appropriate time and resources to address these issues in a proactive manner. This article outlines collaboration strategies for creating an effective culture, governance, and leadership, and provides practical suggestions for optimizing the performance of the urology group practice. PMID- 25118850 TI - Impact of alpha blockers, 5-alpha reductase inhibitors and combination therapy on sexual function. AB - Medical treatments for lower urinary tract symptoms due to benign prostatic hyperplasia are frequently associated with changes in sexual function. While these medications are generally well-tolerated and have both reduced and delayed more invasive surgical options, the ramifications of long-term chronic use are largely unknown. Sexual side effects of these medications are frequently either reported as part of a short-term initial drug study or have inflexible endpoints that are not able to gauge more subtle changes in sexual performance. This review will delineate the currently known effects of these medications on sexual function and will consider mechanisms of dysfunction. PMID- 25118852 TI - Robotic-assisted simple prostatectomy: is there evidence to go beyond the experimental stage? AB - Open simple prostatectomy (OSP) is an effective and durable treatment for select patients with symptomatic benign prostatic hyperplasia (BPH) and large-volume prostate glands (>80 cc), yet is associated with clinically significant risk of bleeding, transfusion, prolonged hospital length of stay (LOS), and complications. Robotic-assisted simple prostatectomy (RASP) potentially reduces intraoperative blood loss and improves perioperative outcomes. Thirteen non comparative series (Level 3 evidence) of RASP have established its safety and efficacy and have demonstrated substantially decreased risk of transfusion, complications, and mean LOS relative to published series of OSP, but with consistently longer operative times. Comparative outcomes data (Level 1 and Level 2 evidence), however, are relatively lacking. Thus, while RASP has advanced beyond the experimental stage, definitive outcomes studies are needed to establish its benefits and costs relative to OSP and transurethral surgery. PMID- 25118853 TI - The evaluation and management of refractory neurogenic overactive bladder. AB - Patients with neurologic disease commonly develop overactive bladder (OAB) symptoms of urgency, frequency, and/or urge incontinence that remain bothersome despite oral pharmacologic therapy. Management of refractory OAB in the neurogenic population is a complex issue with no uniform treatment strategy. When treatment fails or patients generally are dissatisfied with the adverse effects of oral therapy, available options include sacral neuromodulation, percutaneous tibial nerve stimulation (PTNS), botulinum toxin injections, and lower urinary tract reconstruction such as augmentation cystoplasty. A thorough knowledge and understanding of available and emerging treatment options for neurogenic detrusor overactivity is paramount to assisting clinicians in choosing an appropriate treatment. This article reviews the non-pharmacologic treatment options for neurogenic OAB, mainly botulinum toxin, neuromodulation, and lower urinary tract reconstruction, and discusses important relevant studies. PMID- 25118856 TI - Single-molecule electroluminescence and photoluminescence of polyfluorene unveils the photophysics behind the green emission band. AB - Optoelectronic properties of polyfluorene, a blue light-emitting organic semiconductor, are often degraded by the presence of green emission that originates mainly from oxidation of the polymer. Here, we use single-molecule electroluminescence (EL) and photoluminescence (PL) spectroscopy on polyfluorene chains confined in vertical cylinders of a phase-separated block copolymer to spectrally resolve the green band and investigate in detail the photophysical processes responsible for its appearance. In both EL and PL, a substantial fraction of polyfluorene chains shows spectrally stable green emission which is ascribed to a keto defect. In addition, in EL, we observe a new type of vibrationally resolved spectra distributed over a wide range of frequencies and showing strong spectral dynamics. Based on quantum chemical calculations, this type is proposed to originate from charge-assisted formation and stabilization of ground-state aggregates. The results are expected to have broad implications in the fields of photophysics and material design of polyfluorene materials. PMID- 25118855 TI - Neurogenic bladder: from diagnosis to management. AB - Patients with spinal cord injury (SCI) present with a wide range and variety of urologic manifestations, depending upon the level of injury. Historically, patients with spinal cord injury experienced significant mortality related to renal failure. Greater knowledge of the pathophysiology of SCI, however, has contributed to a reduction in mortality. It is essential to perform a thorough initial evaluation and regular follow-up of these patients to achieve the primary goal of preservation of renal function, with the secondary goal of optimizing the patient's quality of life. PMID- 25118858 TI - Erratum to: Positive Affect Processing and Joint Attention in Infants at High Risk for Autism: An Exploratory Study. PMID- 25118854 TI - Surgical management of Peyronie's disease. AB - Peyronie's disease (PD) has a significant impact on the quality of life of both patients and their partners due to the compromised sexual function and physical deformation resulting from the condition. PD is a connective tissue disorder marked by fibrotic healing of the tunica albuginea, leading to penile deformities including curvature, shortening, loss of girth, hourglass appearance, and hinging. Despite the multiple medical therapies available, surgery is the gold standard of treatment once the plaque has stabilized. We present a review of the disease process, preoperative evaluation, operative planning, surgical treatments with outcomes and complications, and nascent developments in surgical management and graft development. Options include tunical lengthening procedures, tunical shortening procedures, and penile prosthesis. Decision-making is governed by degree of curvature, erectile function, and associated penile deformities. In cases with curvature of less than 60-70 degrees, adequate penile length, and no hourglass deformity, patients are candidates for tunical shortening procedures. Patients with curvature greater than 60-70 degrees, penile hourglass or hinge destabilizing deformities, and adequate erectile function should be counseled with regard to tunical lengthening procedures. Patients with poor preoperative erectile function should undergo inflatable penile prosthesis placement, with possible secondary straightening procedures. Technique selection should be based upon surgeon preference, expertise, and experience, as evidence does not necessarily support one procedure over another. PMID- 25118859 TI - In the eyes of residents good supervisors need to be more than engaged physicians: the relevance of teacher work engagement in residency training. AB - During their development into competent medical specialists, residents benefit from their attending physicians' excellence in teaching and role modelling. Work engagement increases overall job performance, but it is unknown whether this also applies to attending physicians' teaching performance and role modelling. Attending physicians in clinical teaching practice take on roles as doctors and teachers. Therefore, this study (a) examined levels of attending physicians' work engagement in both roles, and (b) quantified the relationships of both work engagement roles to their teaching performance and role model status. In this multicenter survey, residents evaluated attending physicians' teaching performance and role model status using the validated System for Evaluation of Teaching Qualities. Attending physicians self-reported their work engagement on a 7-point scale, separately for their roles as doctors and teachers, using the validated 9-item Utrecht Work Engagement Scale. In total, 549 (68 %) residents filled out 4,305 attending physician evaluations and 627 (78 %) attending physicians participated. Attending physicians reported higher work engagement in their doctor than in their teacher roles (mean difference: 0.95; 95 % CI 0.86 1.04; p < 0.001). Teacher work engagement was positively related to teaching performance (regression coefficient, B: 0.11; 95 % CI 0.08-0.14; p < 0.001), which in turn was positively associated to role model status (B: 1.08; 95 % CI 0.10-1.18; p < 0.001). In the eyes of residents, good supervisors need to be more than engaged physicians, as attending physicians with high teacher work engagement were evaluated as better teachers. PMID- 25118860 TI - Identifying longitudinal growth trajectories of learning domains in problem-based learning: a latent growth curve modeling approach using SEM. AB - To determine the direction and extent to which medical student scores (as observed by small-group tutors) on four problem-based-learning-related domains change over nine consecutive blocks during a two-year period (Domains: Problem Solving/Use of Information/Group Process/Professionalism). Latent growth curve modeling is used to analyze performance trajectories in each domain of two cohorts of 1st and 2nd year students (n = 296). Slopes of the growth trajectories show similar linear increments in the first three domains. Further analysis revealed relative strong individual variability in initial scores but not in their later increments. Professionalism, on the other hand, shows low variability and has very small, insignificant slope increments. In this study, we showed that the learning domains (Problem Solving, Use of Information, and Group Process) observed during PBL tutorials are not only related to each other but also develop cumulatively over time. Professionalism, in contrast to the other domains studied, is less affected by the curriculum suggesting that this represents a stable characteristic. The observation that the PBL tutorial has an equal benefit to all students is noteworthy and needs further investigation. PMID- 25118857 TI - Randomized controlled trial comparing gastric cancer screening by gastrointestinal X-ray with serology for Helicobacter pylori and pepsinogens followed by gastrointestinal endoscopy. AB - BACKGROUND: Based on the results of several case-control and cohort studies gastrointestinal X-ray (GI X-ray) has been recommended for use in the nationwide screening program for gastric cancer.. Although this was the only effective screening program when almost all of the Japanese population were Helicobacter pylori (H. pylori) positive, there has been concern whether an alternative effective screening system should be established for the future H. pylori negative generation. We therefore conducted the first randomized controlled trial (RCT) comparing GI X-ray and gastrointestinal endoscopy (GIE) scheduled according to results of serological testing (ST); this was done to determine the potential for an alternative screening method. METHODS: Subjects who fulfilled the inclusion criteria were residents between the ages of 30 and 74 and who were able to receive gastric cancer screening in the Yurihonjo area. Participants were assigned to the GI X-ray group or the GIE-ST group by computer randomization. Subjects in each group were further subdivided into 4 categories according to their different risks for gastric cancer. The feasibility of stratified randomization was serologically assessed and detection rates of gastric cancer at entry by the different screening methods were also compared. RESULTS: Of the 2,962 subjects invited, 1,206 individuals (41 percent) were included in the first stage of this stratified RCT, and 604 and 602 individuals were assigned to the GI X-ray group and the GIE-ST group, respectively. There were no statistically significant differences in sex, age, height, body weight, smoking, alcohol intake and family history of cancer between the 2 groups. During ST the GI X-ray group showed a distribution that was not statistically different from that of the GIE ST group. Although 3 cases of gastric cancer were detected in the GIE-ST group, there was no statistically significant difference between the 2 groups. One complication found was barium aspiration during the examination in the X-ray group. CONCLUSION: We confirmed that baseline demographic features of the 2 groups were well balanced. We are now organizing the first RCT to compare the existing screening method and the alternative method (Clinical trial registration number: UMIN000005962). PMID- 25118861 TI - Community of learners: charting learning in first year graduate entry medical students during problem-based learning (PBL) study. AB - This study considers social learning practices within and outside the overt curriculum. A thematic approach was used to analyse data from six focus group interviews with 11 graduate entry medical students from a UK university over a year of study. The results indicate that: (1) during their first year of study students form a community of learning practice, (2) this community of practice influences learning inside and outside the overt curriculum, (3) there is a changing community profile over the year of practice, (4) the students' engagement in problem-based learning (PBL) as part of their overt curriculum strongly influences the development of a community of practice and hence learning both inside and outside the overt curriculum. Findings are discussed in terms of Wenger's community of practice framework, the role of distributed cognition and social learning. It is concluded that PBL is an effective approach for academics to enrich students' social learning practices. PMID- 25118862 TI - Rituals of Madness in the Practices of Place. AB - While completing a PhD in literature with a focus on the practices of physical and linguistic spaces, I was also working and sleeping (on call) at a dilapidated house in a poorer part of Bristol in case I was needed by one of five paranoid or clinically psychotic residents. I gave out medication in the morning, then went home to study in a small rented room. I began to see ritual everywhere--in my professors' routines; my own habits; the behaviours of the mentally ill patients. This paper is the story of a number of madnesses and the problems with reading ritual performance in everything we do. PMID- 25118863 TI - Fairness norms and theory of mind in an ultimatum game: judgments, offers, and decisions in school-aged children. AB - The sensitivity to fairness undergoes relevant changes across development. Whether such changes depend on primary inequity aversion or on sensitivity to a social norm of fairness is still debated. Using a modified version of the Ultimatum Game that creates informational asymmetries between Proposer and Responder, a previous study showed that both perceptions of fairness and fair behavior depend upon normative expectations, i.e., beliefs about what others expect one should do in a specific situation. Individuals tend to comply with the norm when risking sanctions, but disregard the norm when violations are undetectable. Using the same methodology with children aged 8-10 years, the present study shows that children's beliefs and behaviors differ from what is observed in adults. Playing as Proposers, children show a self-serving bias only when there is a clear informational asymmetry. Playing as Responders, they show a remarkable discrepancy between their normative judgment about fair procedures (a coin toss to determine the offer) and their behavior (rejection of an unfair offer derived from the coin toss), supporting the existence of an outcome bias effect. Finally, our results reveal no influence of theory of mind on children's decision-making behavior. PMID- 25118866 TI - Difficult needle decompression of bilateral tension pneumothoraces in an obese female patient. PMID- 25118865 TI - Evolution of inspiratory diaphragm activity in children over the course of the PICU stay. AB - PURPOSE: Diaphragm function should be monitored in critically ill patients, as full ventilatory support rapidly induces diaphragm atrophy. Monitoring the electrical activity of the diaphragm (EAdi) may help assess the level of diaphragm activity, but such monitoring results are difficult to interpret because reference values are lacking. The aim of this study was to describe EAdi values in critically ill children during a stay in the pediatric intensive care unit (PICU), from the acute to recovery phases, and to assess the impact of ventilatory support on EAdi. METHODS: This was a prospective longitudinal observational study of children requiring mechanical ventilation for >=24 h. EAdi was recorded using a validated method in the acute phase, before extubation, after extubation, and before PICU discharge. RESULTS: Fifty-five critically ill children were enrolled in the study. Median maximum inspiratory EAdi (EAdimax) during mechanical ventilation was 3.6 [interquartile range (IQR) 1.2-7.6] MUV in the acute phase and 4.8 (IQR 2.0-10.7) MUV in the pre-extubation phase. Periods of diaphragm inactivity (with no detectable inspiratory EAdi) were frequent during conventional ventilation, even with a low level of support. EAdimax in spontaneous ventilation was 15.4 (IQR 7.4-20.7) MUV shortly after extubation and 12.6 (IQR 8.1-21.3) MUV before PICU discharge. The difference in EAdimax between mechanical ventilation and post-extubation periods was significant (p < 0.001). Patients intubated mainly because of a lung pathology exhibited higher EAdi (p < 0.01), with a similar temporal increase. CONCLUSIONS: This is the first systematic description of EAdi evolution in children during their stay in the PICU. In our patient cohort, diaphragm activity was frequently low in conventional ventilation, suggesting that overassistance or oversedation is common in clinical practice. EAdi monitoring appears to be a helpful tool to detect such situations. PMID- 25118867 TI - Pathergy phenomenon: huge pyoderma gangrenosum following tube thoracostomy. PMID- 25118869 TI - A large vertebral artery pseudoaneurysm due to percutaneous internal jugular vein cannulation. PMID- 25118868 TI - Mortality related to after-hours discharge from intensive care in Australia and New Zealand, 2005-2012. AB - INTRODUCTION: After-hours discharge from the intensive care unit (ICU) is associated with adverse patient outcomes including increased ICU readmissions and mortality. Since Australian and New Zealand data were last published, overall ICU patient mortality has decreased; however it is unknown whether changes in discharge practices have contributed to these improved outcomes. Our aim was to examine trends over time in discharge timing and the contemporary associations with mortality and ICU readmission. METHODS: Retrospective cohort study using data from the Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS APD) for patients admitted to Australian and New Zealand ICUs between January 2005 and December 2012. Data collected included patient characteristics, time of ICU discharge, hospital mortality and ICU readmissions. RESULTS: Between 1 January 2005 and 31 December 2012, there were 710,535 patients available for analysis, of whom 109,384 (15.4 %) were discharged after-hours (1800-0600 hours). There were no changes in timing of ICU discharge over the 8 years of the study. Patients discharged after-hours had a higher hospital mortality (6.4 versus 3.6 %; P < 0.001) and more ICU readmissions (5.1 versus 4.5 %; P < 0.001) than patients discharged in-hours. Although post-ICU mortality for all patients declined during the study period, the risk associated with after hours discharge remained elevated throughout (odds ratio 1.34, 95 % confidence intervals 1.30-1.38). CONCLUSIONS: After-hours discharge remains an important independent predictor of hospital mortality and readmission to ICU. Despite widespread dissemination this evidence has not translated into fewer after-hours discharges or reduction in risk in Australian and New Zealand hospitals. PMID- 25118870 TI - Silk fibroin/collagen and silk fibroin/chitosan blended three-dimensional scaffolds for tissue engineering. AB - INTRODUCTION: In this study, the silk fibroin blended constructs were produced, scaffold performances of different kinds of scaffold were analyzed, and the better type for tissue engineering was optimized. METHODS: The silk fibroin/collagen (SF/C) and silk fibroin/chitosan (SF/CS) were made using a freeze-drying technique, porosity, water absorption expansion rate, mechanical properties and pore size of different scaffold was detected. Bone marrow mesenchymal stem cells (BMSCs) of 4-week-old male Wistar rats were separated by density gradient centrifugation, third generation BMSCs were seeded onto scaffolds, cultured 14 days, proliferation and metabolize of cells were detected in different time using the thiazolyl blue tetrazolium bromide (MTT) assay method, and cell morphology and distribution were observed by histological analysis and scanning electron microscopy (SEM). RESULTS: Porosity, water absorption expansion rate and Young's modulus of SF/C were significantly higher than SF/CS (p < 0.05); pore size of SF/C and SF/CS was 103 +/- 12 and 76 +/- 11 MUm and had no significant differences between two types (p > 0.05); MTT results showed that the metabolism of cells in the SF/C was better than SF/CS; after cultivation for 14 days, in the inner zone of scaffolds, cells staining were little or absent from SF/CS, lots of cells staining were existing in SF/C; pore size was consistent, holes communicated with each other better, stem cells grew well inside the scaffolds, extended fully and secreted much extracellular matrix under SEM in SF/C scaffold; internal structure of SF/CS was disorder, holes size were not consistent, and did not communicated with each other and cells were partly dead. CONCLUSION: Compared with SF/CS, SF/C scaffold showed better porosity, water absorption expansion rate, elasticity modulus and pore size, cells grow well inside the scaffolds, and was more suitable for tissue engineering. PMID- 25118871 TI - Calcineurin-mediated regulation of hyphal growth, septation, and virulence in Aspergillus fumigatus. AB - Calcineurin is a heterodimeric protein phosphatase complex composed of catalytic (CnaA) and regulatory (CnaB) subunits and plays diverse roles in regulating fungal stress responses, morphogenesis, and pathogenesis. Fungal pathogens utilize the calcineurin pathway to survive in the host environment and cause life threatening infections. The immunosuppressive calcineurin inhibitors (FK506 and cyclosporine A) are active against fungi, making calcineurin a promising antifungal drug target. Here, we review novel findings on calcineurin localization and functions in Aspergillus fumigatus hyphal growth and septum formation through regulation of proteins involved in cell wall biosynthesis. Extensive mutational analysis in the functional domains of A. fumigatus CnaA has led to an understanding of the relevance of these domains for the localization and function of CnaA at the hyphal septum. An evolutionarily conserved novel mode of calcineurin regulation by phosphorylation in filamentous fungi was found to be responsible for virulence in A. fumigatus. This finding of a filamentous fungal specific mechanism controlling hyphal growth and virulence represents a potential target for antifungal therapy. PMID- 25118872 TI - Aspergillus: sex and recombination. AB - The genus Aspergillus is one of the most widespread groups of fungi on Earth, comprised of about 300-350 species with very diverse lifestyles. Most species produce asexual propagula (conidia) on conidial heads. Despite their ubiquity, a sexual cycle has not yet been identified for most of the aspergilli. Where sexual reproduction is present, species exhibit either homothallic (self fertile) or heterothallic (obligate outcrossing) breeding systems. A parasexual cycle has also been described in some Aspergillus species. As in other fungi, sexual reproduction is governed by mating-type (MAT) genes, which determine sexual identity and are involved in regulating later stages of sexual development. Previous population genetic studies have indicated that some supposedly asexual aspergilli exhibit evidence of a recombining population structure, suggesting the presence of a cryptic sexual cycle. In addition, genome analyses have revealed networks of genes necessary for sexual reproduction in several Aspergillus species, again consistent with latent sexuality in these fungi. Knowledge of MAT gene presence has then successfully been applied to induce sexual reproduction between MAT1-1 and MAT1-2 isolates of certain supposedly asexual aspergilli. Recent progress in understanding the extent and significance of sexual reproduction is described here, with special emphasis on findings that are relevant to clinically important aspergilli. PMID- 25118873 TI - Killed Saccharomyces cerevisiae protects against lethal challenge of Cryptococcus grubii. AB - Heat-killed Saccharomyces cerevisiae (HKY) vaccination protects mice against aspergillosis, coccidioidomycosis, mucormycosis, or candidiasis. We studied HKY protection against murine cryptococcosis. Once weekly subcutaneous HKY doses (S, 6 * 10(7); 2S, 1.2 * 10(8); 3S, 2.4 * 10(8)) began 28 (*3), 35 (*4), or 42 (*6) days prior to intravenous Cryptococcus grubii infection. Survival through 28 days, and CFU in the organs of survivors, were compared to saline-vaccinated controls. In the initial experiment, S, S*4, or 2S reduced brain CFU; liver or spleen CFU was reduced by S*4 or 2S. In a more lethal second experiment, 2S*6, 2S, or 3S*4 improved survival, and HKY regimens reduced CFU in the brain, liver, or spleen, with 2S*6, 2S, or 3S*4 most efficacious. Dose size appears more important than the number of doses: Regimens >S were superior, and 2S and 2S*6 were equivalent. 2S and 3S were equivalent, suggesting doses >2S do not provide additional protection. HKY protects against Cryptococcus, supporting components of HKY as a basis for the development of a panfungal vaccine. PMID- 25118874 TI - Killing rates for caspofungin against Candida albicans after brief and continuous caspofungin exposure in the presence and absence of serum. AB - It was previously demonstrated that brief (<=1 h) exposures to echinocandins are as effective to kill Candida albicans cells as continuous 24-h exposure. However, killing rates after continuous and short (1 h) echinocandin exposures to C. albicans have not yet been evaluated in RPMI-1640 with and without 50 % serum. We evaluated four echinocandin susceptible C. albicans bloodstream isolates, ATCC 10231 type strain and an echinocandin-resistant isolate (DPL20, FKS F645P). Caspofungin MICs, time-kill and postantifungal effect (PAFE) tests were performed in RPMI-1640 with and without 50 % serum. Killing rates (k values) in time-kill and PAFE experiments were determined for each strain and concentration. In time kill experiments, colony count decreases were isolate- and concentration dependent at 0.25, 1, 4, 8, 16 and 32 mg/L in RPMI-1640, but concentration independent at 1, 4, 8, 16 and 32 mg/L in 50 % serum. One-hour caspofungin exposure at 4, 16 and 32 mg/L resulted in CFU decreases comparable with the results obtained in time-kill experiments in RPMI-1640, but 50 % serum at 4, 16 and 32 mg/L allowed growth of all isolates (k values were negative) (P < 0.05 0.001). PAFE in 50 % serum decreased markedly at 4, 16 and 32 mg/L. Killing rates remained high and concentration-independent in 50 % serum in case of continuous but not in case of brief caspofungin exposure. As only a short growth inhibition without killing was observed in 50 % serum, clinical relevance of caspofungin PAFE in vivo is questionable. PMID- 25118875 TI - Prevalence of Candida nivariensis and Candida bracarensis in vulvovaginal Candidiasis. AB - Candida nivariensis and Candida bracarensis were isolated from patients with vulvovaginal candidiasis (VVC). Candida nivariensis and Candida bracarensis were found in presumptive Candida glabrata isolates, which were identified using the API Candida system. We retrospectively re-examined vaginal presumptive Candida glabrata isolates for Candida nivariensis and Candida bracarensis from January 1, 2003, through December 31, 2012, via detection of the ITS1 region and the 5.8S ribosomal RNA gene. Among 301 presumptive Candida glabrata isolates, 293 isolates were confirmed as C. glabrata (97.34 %), 7 isolates were identified as C. nivariensis (2.33 %) and 1 isolate was identified as C. bracarensis (0.33 %). The C. nivariensis and C. bracarensis isolates were confirmed by sequencing. All C. nivariensis isolates were susceptible to nystatin and susceptible or susceptible dose-dependent to fluconazole, itraconazole, miconazole, and clotrimazole. The C. bracarensis isolate was susceptible to nystatin and the tested azoles. Among the seven patients with VVC caused by C. nivariensis and who were treated with various antifungal agents, only one patient achieved mycological eradication at both the day 7-14 and day 30-35 follow-ups. The C. bracarensis isolate was isolated from a symptomatic pregnant woman; additional data for this patient were unavailable. We conclude that C. nivariensis and C. bracarensis existed in the vaginal samples of patients with VVC. Therapeutic efficacy in the patients with C. nivariensis was poor and inconsistent with the observed in vitro antifungal susceptibility, which requires further study. PMID- 25118876 TI - Single-stage supramalleolar osteotomy for coronal plane deformity. AB - A variety of surgical procedures are utilized for management of ankle osteoarthritis. The most common etiology in patients with ankle osteoarthritis is post-traumatic often resulting in asymmetric ankle osteoarthritis with concomitant valgus or varus deformity. A substantial part of tibiotalar joint is often preserved, therefore, in appropriate patients, joint-preserving surgery holds the potential to be a superior treatment option than joint-sacrificing procedures including total ankle replacement or ankle arthrodesis. This review is designed to describe indications and contraindications for single-stage supramalleolar realignment surgery. Complications associated with this type of surgery and postoperative outcome are highlighted using recent literature. PMID- 25118878 TI - Osteoporosis and the risk of symptomatic nephrolithiasis: a population-based 5 year follow-up study in Taiwan. AB - This study estimates the risk of symptomatic nephrolithiasis within 5 years of newly diagnosed osteoporosis in a Taiwan population. This cohort study consisted of patients with a diagnosis of osteoporosis between Jan. 2003 and Dec. 2005 (N = 1634). Four age- and gender- matched patients for every patient in the study cohort were selected using random sampling as the comparison cohort (N = 6536). All patients were tracked for 5 years from the date of cohort entry to identify whether they developed symptomatic nephrolithiasis. Cox proportional hazard regressions were performed to evaluate the 5-year nephrolithiasis-free survival rates. During the 5-year follow-up period, 60 osteoporosis patients (3.7%) and 165 non- osteoporosis patients (2.5%) developed symptomatic nephrolithiasis. The adjusted HR of symptomatic nephrolithiasis was 1.38 times greater risk for patients with osteoporosis than for the comparison cohort (95% confidence interval (CI) 1.03-1.86; P < .05). Osteoporosis is very likely to be an independent risk factor for subsequent diagnosis of symptomatic nephrolithiasis. PMID- 25118877 TI - The prevalence of workaholism: a survey study in a nationally representative sample of Norwegian employees. AB - Workaholism has become an increasingly popular area for empirical study. However, most studies examining the prevalence of workaholism have used non-representative samples and measures with poorly defined cut-off scores. To overcome these methodological limitations, a nationally representative survey among employees in Norway (N = 1,124) was conducted. Questions relating to gender, age, marital status, caretaker responsibility for children, percentage of full-time equivalent, and educational level were asked. Workaholism was assessed by the use of a psychometrically validated instrument (i.e., Bergen Work Addiction Scale). Personality was assessed using the Mini-International Personality Item Pool. Results showed that the prevalence of workaholism was 8.3% (95% CI = 6.7-9.9%). An adjusted logistic regression analysis showed that workaholism was negatively related to age and positively related to the personality dimensions agreeableness, neuroticism, and intellect/imagination. Implications for these findings are discussed. PMID- 25118883 TI - Voyage to the bottom of the 'seaquence'. PMID- 25118879 TI - Augmented efficacy with the combination of blockade of the Notch-1 pathway, bortezomib and romidepsin in a murine MT-1 adult T-cell leukemia model. AB - Adult T-cell leukemia (ATL) is an aggressive malignancy caused by human T-cell lymphotropic virus-1. There is no accepted curative therapy for ATL. We have reported that certain ATL patients have increased Notch-1 signaling along with constitutive activation of the nuclear factor-kappaB pathway. Physical and functional interaction between these two pathways provides the rationale to combine the gamma-secretase inhibitor compound E with the proteasome inhibitor bortezomib. Moreover, romidepsin, a histone deacetylase inhibitor, has demonstrated major antitumor action in leukemia/lymphoma. In this study, we investigated the therapeutic efficacy of the single agents and the combination of these agents in a murine model of human ATL, the MT-1 model. Single and double agents inhibited tumor growth as monitored by tumor size (P<0.05), and prolonged survival of leukemia-bearing mice (P<0.05) compared with the control group. The combination of three agents significantly enhanced the antitumor efficacy as assessed by tumor size, tumor markers in the serum (human soluble interleukin-2 receptor-alpha and beta2-microglobulin) and survival of the MT-1 tumor-bearing mice, compared with all other treatment groups (P<0.05). Improved therapeutic efficacy obtained by combining compound E, bortezomib and romidepsin supports a clinical trial of this combination in the treatment of ATL. PMID- 25118884 TI - RAB11-mediated trafficking in host-pathogen interactions. AB - Many bacterial and viral pathogens block or subvert host cellular processes to promote successful infection. One host protein that is targeted by invading pathogens is the small GTPase RAB11, which functions in vesicular trafficking. RAB11 functions in conjunction with a protein complex known as the exocyst to mediate terminal steps in cargo transport via the recycling endosome to cell-cell junctions, phagosomes and cellular protrusions. These processes contribute to host innate immunity by promoting epithelial and endothelial barrier integrity, sensing and immobilizing pathogens and repairing pathogen-induced cellular damage. In this Review, we discuss the various mechanisms that pathogens have evolved to disrupt or subvert RAB11-dependent pathways as part of their infection strategy. PMID- 25118885 TI - Uniting the classification of cultured and uncultured bacteria and archaea using 16S rRNA gene sequences. AB - Publicly available sequence databases of the small subunit ribosomal RNA gene, also known as 16S rRNA in bacteria and archaea, are growing rapidly, and the number of entries currently exceeds 4 million. However, a unified classification and nomenclature framework for all bacteria and archaea does not yet exist. In this Analysis article, we propose rational taxonomic boundaries for high taxa of bacteria and archaea on the basis of 16S rRNA gene sequence identities and suggest a rationale for the circumscription of uncultured taxa that is compatible with the taxonomy of cultured bacteria and archaea. Our analyses show that only nearly complete 16S rRNA sequences give accurate measures of taxonomic diversity. In addition, our analyses suggest that most of the 16S rRNA sequences of the high taxa will be discovered in environmental surveys by the end of the current decade. PMID- 25118886 TI - The impact of various platelet indices as prognostic markers of septic shock. AB - INTRODUCTION: Platelet indices, including mean platelet volume (MPV), are readily available blood tests, although their prognostic value in patients with septic shock has not been fully explored. Current evidence has found contradictory results. This study aims to explore the behavior of platelet indices in septic shock and their clinical prognostic value. METHODS: Charts of septic shock patients from January to December 2012 in a tertiary medical center in Northern China were reviewed retrospectively. Platelet indices were recorded during the first five consecutive days after admission, as well as the penultimate and the last day of hospital stay. The data were compared between surviving and non surviving patients. RESULTS: A total of 124 septic shock patients were enrolled. Thirty-six of the patients survived and 88 of them expired. MPV in the non survivor group was higher than that of the survivor group, especially on the last day. PDW and PLCR showed increased trends, while PCT and PLT decreased in the non survivor group. Among the PLT indices, MPV had the highest area under the receiver operating characteristic curve (0.81) with a precision rate of 75.6% at a cut-off of 10.5.Compared with other more usual septic shock prognostic markers, MPV is second only to lactate for the highest area under the curve. CONCLUSION: A statistically significant difference was seen between survivors and non-survivors for platelet indices which make them easily available and useful prognostic markers for patients in septic shock. PMID- 25118887 TI - Megakaryocytic potentiating factor and mature mesothelin stimulate the growth of a lung cancer cell line in the peritoneal cavity of mice. AB - The mesothelin (MSLN) gene encodes a 71 kilodalton (kDa) precursor protein that is processed into megakaryocytic potentiating factor (MPF), a 31 kDa protein that is secreted from the cell, and mature mesothelin (mMSLN), a 40 kDa cell surface protein. The mMSLN binds to CA125, an interaction that has been implicated in the intra-cavitary spread of mesothelioma and ovarian cancer. To better define the role of MPF and mMSLN, growth of the lung cancer cell line A549 was evaluated in immuno-deficient mice with inactivation of the Msln gene. We observed that Msln-/ mice xenografted with intraperitoneal A549 tumors survive significantly long than tumor-bearing Msln+/+ mice. When tumor-bearing Msln-/- mice are supplemented with recombinant MPF (and to a lesser extent mMSLN), most of this survival advantage is lost. These studies demonstrate that MPF and mMSLN have an important role in the growth of lung cancer cells in vivo and raise the possibility that inactivation of MPF may be a useful treatment for lung and other MSLN expressing cancers. PMID- 25118888 TI - Protective effect of magnesium and metformin on endometrium and ovary in experimental diabetes mellitus. AB - We evaluated the effect of magnesium and metformin on streptozotocin (STZ) induced diabetes mellitus (DM) in non-pregnant female rats. The study comprised four groups, each consisting of eight, non-pregnant, adult Wistar female rats with a weight range of 170-250 g, maintained under the usual laboratory conditions. One group of female rats was the control group that received no treatment. To induce DM, the other three groups of animals received streptozotocin (STZ), 60 mg/kg i.p. (in a single dose). The first STZ group received no additional treatment. The second group received MgCl2 1 mmol/kg/day i.p. daily, for eight weeks. The third group received daily metformin, 100 mg/kg/day per os (endogastric probe), for eight weeks. Blood glucose, total plasma magnesium concentrations, and oxidative status were determined prior to, 24 hours and eight weeks after administration of the STZ. After eight weeks of treatment, the animals were anesthetized and sacrificed. The uterus and ovaries were removed and examined under optical microscopy. The data obtained were analyzed statistically using the ANOVA test. The results showed that the number of atretic ovarian follicles was 84%higher in the STZ-induced diabetes group compared to the control group (p<0.01). The number of atretic follicles found in the group receiving daily MgCl2 was 32% higher compared to the untreated control group (p<0.05). The number of atretic follicles was increased by only 27% in the metformin-treated group, as compared with the untreated control group.. The STZ induced diabetes group presented an endometrial epithelial atrophy not seen in the control group. MgCl2 administration attenuated the degree of endometrial atrophy, there being an endometrial epithelial thickness of 19.43 +/- 0.51 MUm in the STZ+MgCl2 group (p<0.05), as compared to a thickness of 13.51 +/- 0.27 MUm in the STZ only-treated diabetic group. PMID- 25118889 TI - BABYSCAN: a whole body counter for small children in Fukushima. AB - BABYSCAN, a whole body counter for small children with a detection limit for (137)Cs of better than 50 Bq/body, was developed, and the first unit has been installed at a hospital in Fukushima, to help families with small children who are very much concerned about internal exposures. The design principles, implementation details and the initial operating experience are described. PMID- 25118890 TI - Correction-less dosimetry of nonstandard photon fields: a new criterion to determine the usability of radiation detectors. AB - In the IAEA-AAPM dosimetry formalism, detector measurements in general nonstandard conditions are corrected using the factor k(f(clin),f(msr))(Q(clin),Q(msr)). This factor needs to be evaluated on a case-by case basis which is difficult to accomplish in practice. The present paper aims to provide a method that allows neglecting correction factors for small and composite IMRT fields by first determining a radiation detector's usability in these fields. Detailed models of nine radiation detectors are built: four ionization chambers (NE2571, A12, A1SL, A14), three small field detectors (PTW31018 microLion, PTW60003 natural diamond, PTW60012 unshielded diode) and two near water-equivalent detectors (alanine, W1 scintillating fiber). Using the egs_chamber Monte Carlo code, dose response functions at 6 MV and 25 MV are sampled for each detector and their corresponding volume of water. These functions are then used with a newly derived criterion to evaluate an upper bound xi(f(ns),f(msr))(Q(ns),Q(msr)) on the variable epsilon(f(ns),f(msr))(Q(ns),Q(msr)) if no field collimation/modulation occurs over a given perturbation zone. The variable epsilon(f(ns),f(msr))(Q(ns),Q(msr)) is defined as the absolute value of the relative deviation from unity of a nonstandard field quality correction factor k(f(ns),f(msr))(Q(ns),Q(msr)). Using the same criterion, perturbation zones are evaluated by finding the smallest field size allowed for correction-less dosimetry with a given tolerance xi(f(ns),f(msr))(Q(ns),Q(msr)). For composite fields, the sensitivity of detectors to the non-uniformity of virtual symmetric collapsed beams over regions of interest specified by the criterion is studied to estimate an upper bound xi (f(ns),f(ref))(Q(ns),Q) on epsilon(f(ns),f(ref))(Q(ns),Q) for a given beam flatness. Finally, a newly defined perturbation function is used to minimize the perturbations of the microLion chamber through density compensation. The theoretical criterion shows good agreement with full Monte Carlo simulations of epsilon(f(ns),f(msr))(Q(ns) Q(msr)). Perturbation zones are shown to be sensitive to both the energy of the beam and the orientation of the detector. The density compensated microLion shows significantly improved response in both axial and radial orientations in small and composite IMRT fields. Finally, the new Exradin W1 scintillator is shown to have xi(f(ns),f(msr))(Q(ns),Q(msr)) values under 1% in small fields. The methods presented in this work theoretically show that correction-less dosimetry of nonstandard field can be accomplished by knowing the limit of usability of radiation detectors in these conditions. Potential applications include small field output factor measurements and absolute absorbed dose to water verification in the QA of clinical IMRT fields. PMID- 25118891 TI - Association of cystatin C with measures of obesity and its impact on cardiovascular events among healthy US adults. AB - BACKGROUND: This study sought to explore the relationship between cystatin C (CysC) and anthropometric measures of obesity and the influence of this association on mortality [cardiovascular disease (CVD), coronary heart disease, and all-cause] in a nationally representative population free of CVD, diabetes mellitus, and macroalbuminuria (MA). METHODS: The study cohort included 4577 adult participants of the Third National Health and Nutrition Examination Survey (NHANES). Spearman correlation analysis was performed to ascertain the association between various anthropometric measures and CysC. Formal statistical analyses of the interaction term between anthropometric measures and CysC for outcomes were performed followed by stratified multivariate Cox proportional hazard analyses. RESULTS: A moderate degree of association was seen between CysC and measures of visceral adiposity as represented by waist-to-height ratio (WHR) and waist circumference (WC) and only a weak association between CysC and body mass index (BMI). CysC was predictive of all study outcomes in individuals with normal anthropometric measurements only. CONCLUSIONS: CysC correlated better with measures of visceral adiposity (WC and WHR) compared to BMI and appears to be a better predictor of adverse cardiovascular outcomes among those with anthropometric measures not suggestive of obesity compared to those with abnormal measures of anthropometry. PMID- 25118892 TI - Comments on the paper "Modelling of cell killing due to sparsely ionizing radiation in normoxic and hypoxic conditions and an extension to high LET radiation" by A. Mairani et al., Int. J. Radiat. Biol. 89(10), 2013, 782-793. PMID- 25118893 TI - Short-term effects of extremely low frequency electromagnetic fields exposure on Alzheimer's disease in rats. AB - PURPOSE: With the development and widespread use of electromagnetic field (EMF) technology, recent studies are focusing on the effects of EMF on human health. Recently, extremely low frequency electromagnetic fields (ELF-EMF) have been studied with great interest due to their possible effects on Alzheimer's disease (AD). The objective of the present study was to investigate the interaction between ELF-EMF exposure and memory impairment in rats. MATERIALS AND METHODS: Twenty healthy male Sprague Dawley (SD) rats were randomly divided into two groups (n = 10). Animals were exposed to 100 MUT/50 Hz ELF-EMF or subjected to sham exposure when 12 weeks old. After 12 weeks, the Morris water maze (MWM) was used to test the changes in cognitive and memory ability. Amyloid-beta (Abeta) content in cortex, hippocampus and plasma were measured by ELISA assays. The morphology of neuron was detected by H&E staining. RESULTS: After exposure, the body weight of rats showed no difference compared with the control group. The application of ELF-EMF did not induce any cognitive and memory impairment compared with the sham-exposure group. The determination of Abeta showed no significant change between the two groups, and there was no histological change in ELF-EMF exposure group. CONCLUSION: The present study indicated that short term exposure of 100 MUT/50 Hz ELF-EMF had no effects on cognition and memory of rats, and did not alter the expression of Abeta and the neuron morphology. However, more comprehensive studies are still required to elucidate the possible effects and underlying mechanisms of ELF-EMF exposure on living organisms. PMID- 25118896 TI - Poly(ADP-ribose) polymerase-1 (PARP1) and p53 labelling index correlates with tumour grade in meningiomas. AB - Meningiomas are one of the most frequent intracranial tumours, with 13 histological types and three grades according to the 2007 WHO Classification of Tumours of the Central Nervous System. p53, as one of the most potent tumour suppressor proteins, plays a role in nearly 50% of human tumours. Poly(ADP ribose) polymerase (PARP) is a DNA repair enzyme with high ATP demand. It plays a role in apoptosis by activating an apoptosis inducing factor, and in necrosis by consuming NAD+ and ATP. Only PARP1 has been investigated in detail in tumours out of the 17 members of the PARP superfamily; however, its role has not been studied in meningiomas yet. The aim of this study was to determine the role of p53 and PARP1 in meningiomas of different grade and to establish whether there is any correlation between the p53 and PARP1 expression. Both PARP1 and p53 have been expressed in all examined meningiomas. PARP1 labelled grade II tumours with a higher intensity as compared to grade I and III neoplasms, respectively. An increased p53 expression was noted in grade III meningiomas. There was no statistical correlation between p53 and PARP1 expression. Our data indicate that both PARP1 and p53 activation is a feature in meningiomas of higher grade, PARP1 overexpression being an early, whereas p53 overexpression, a late event in tumour progression. PMID- 25118895 TI - Blocking TRPV1 in nucleus accumbens inhibits persistent morphine conditioned place preference expression in rats. AB - The function of TRPV1 (transient receptor potential vanilloid subfamily, member 1) in the central nervous system is gradually elucidated. It has been recently proved to be expressed in nucleus accumbens (NAc), a region playing an essential role in mediating opioid craving and taking behaviors. Based on the general role of TRPV1 antagonist in blocking neural over-excitability by both pre- and post synaptic mechanisms, TRPV1 antagonist capsazepine (CPZ) was tested for its ability to prohibit persistent opioid craving in rats. In the present study, we assessed the expression of TRPV1 in nucleus accumbens and investigated the effect of CPZ in bilateral nucleus accumbens on persistent morphine conditioned place preference (mCPP) in rats. We also evaluated the side-effect of CPZ on activity by comparing cross-beam times between groups. We found that morphine conditioned place preference increased the TRPV1 expression and CPZ attenuated morphine conditioned place preference in a dose-dependent and target-specific manner after both short- and long-term spontaneous withdrawal, reflected by the reduction of the increased time in morphine-paired side. CPZ (10 nM) could induce prolonged and stable inhibition of morphine conditioned place preference expression. More importantly, CPZ did not cause dysfunction of activity in the subjects tested, which indicates the inhibitory effect was not obtained at the sacrifice of regular movement. Collectively, these results indicated that injection of TRPV1 antagonist in nucleus accumbens is capable of attenuating persistent morphine conditioned place preference without affecting normal activity. Thus, TRPV1 antagonist is one of the promising therapeutic drugs for the treatment of opioid addiction. PMID- 25118897 TI - Neuroprotective properties of ciliary neurotrophic factor on retinoic acid (RA) predifferentiated SH-SY5Y neuroblastoma cells. AB - Ciliary neurotrophic factor (CNTF) is a neurocytokine, which could promote survival and/or differentiation in many cell types. In this study, the biological effects of CNTF on retinoic acid (RA)-predifferentiated SH-SY5Y neuroblastoma cells and the underlying molecular mechanism of this effect were investigated for the first time. The results showed that RA was able to increase cells susceptibility to CNTF via regulating the expression levels of CNTF receptors. A further study revealed that CNTF could induce phosphorylation of STAT3, Akt and ERK1/2 in RA-predifferentiated SH-SY5Y neuroblastoma cells, while the promoting activity of CNTF on survival and neurite growth of cells was attenuated by co treatment with JAK2 inhibitor AG490 (25 MUM), STAT3 inhibitor Curcumin (50 MUM), PI3K inhibitor LY-294002 (50 uM), but not by co-treatment with MEK inhibitor PD98059 (50 MUM). These findings suggested that JAK2/STAT3, as well as PI3K/Akt, play important roles in mediating the survival and neurite growth response of RA predifferentiated cells to CNTF. Our study may be useful to further understand the functional role of CNTF and offer a convenient model to explore the therapeutic potential of CNTF in neurodegenerative diseases. PMID- 25118898 TI - Anaplastic transformation of low-grade gliomas (WHO II) on magnetic resonance imaging. AB - INTRODUCTION: Malignant transformation among gliomas WHO II ranges between 35% and 89%. However, according to some reports, all gliomas WHO II undergo such transformation over time. The aim of the study was to analyse MRI parameters indicating anaplastic transformation of gliomas WHO II. MATERIAL AND METHODS: Forty-six consecutive patients were enrolled in the study (20 females and 26 males; range of age 36 +/- 9 years) with supratentorial glioma WHO II. Multiparametric MR examination included morphological imaging, perfusion-weighted imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy. Group division depended on the course of disease (ST - stable group, AT - anaplastic transformation group). RESULTS: Subtotal tumour resection was achieved in the whole AT group, whereas in the ST group, total tumour resection was achieved in 10/29 (34%) patients. The size of the residual tumour after surgery was statistically significantly higher in the AT group compared to the ST group (AT: 51.5 cm3 +/- 37.7 vs. ST: 29.0 cm3 +/- 37.9; p = 0.011). Contrast enhancement in the AT group occurred in 5/11 (45%) of tumours and in none of the patients' areas of contrast enhancement were resected during surgery/biopsy. However, the initial MR showed contrast enhancement in 10/29 (34%) of patients in the ST group. The areas of contrast enhancement were totally resected in all patients. Compared to the ST group tumours that underwent anaplastic transformation had statistically significantly higher values of mean nrCBV and max nrCBV on the initial MR, the follow-up and final MR examinations. However, statistically significant differences between the groups in ADC values were observed on the follow-up and final MR whereas mean Cho/Cr and mean Cho/NAA were observed as late as on the final MR examination. CONCLUSIONS: Multiparametric MR examination allows the detection of LGGs with high probability of rapid anaplastic transformation and the detection of transformation prior to the occurrence of contrast enhancement. The value of nrCBV is the most useful in the diagnosis of anaplastic transformation. The resection of contrast enhancement area of the tumour significantly increases time to anaplastic transformation of LGGs. PMID- 25118899 TI - Secretory meningiomas: immunohistochemical pattern of lectin and ultrastructure of pseudopsammoma bodies. AB - Secretory meningioma is an infrequent histological subtype of benign, WHO grade I meningioma, that is characterized by focal epithelial and secretory transformation of meningothelial cells. The leading histopathological feature of neoplastic tissue is the presence of eosinophilic hyaline inclusions, defined as "pseudopsammoma bodies". These inclusions are mostly intracytoplasmic, different in size and often multiple. They are stained with periodic acid-Schiff (PAS) and are immunopositive for epithelial and secretory markers. The aim of this study was to determine the pattern of lectin bindings and ultrastructural features of secretory meningiomas. The examination was performed on 8 cases of secretory meningiomas that occurred in women and were mostly associated with prominent peritumoural oedema. Histologically, the tumours exhibited numerous eosinophilic, PAS positive pseudopsammoma bodies. Immunohistochemical studies revealed a strong, ring-like cytokeratin expression around the pseudopsammoma bodies. The inclusions were CEA and EMA positive but negative for vimentin. The immunolabeling with four lectins (PNA, SBA, Con A and DBA) was studied. The majority of pseudopsammoma bodies and surrounding tumour cells were strongly labelled with PNA and SBA. Immunolabelling with Con A showed irregular staining with high intensity in small inclusions. Immunostaining with DBA was seldom positive in inclusions and negative in the tumour cell cytoplasm. Ultrastructure of pseudopsammoma bodies exhibited advanced heterogeneity. The size of inclusions and the content of intracytoplasmic lumina varied greatly. Some pseudopsammoma bodies seemed to be located extracellularly and lacked the obvious lumina. Our ultrastructural study and lectin binding pattern support the unique epithelial and secretory transformation of neoplastic cells connected with their altered glycosylation. PMID- 25118900 TI - Effects of hypothermia on ex vivo microglial production of pro- and anti inflammatory cytokines and nitric oxide in hypoxic-ischemic brain-injured mice. AB - INTRODUCTION: Activated microglia produce neurotoxic factors, including pro inflammatory cytokines and nitric oxide (NO), in response to neuronal destruction. Therapeutic suppression of microglial release of these factors by various approaches including hypothermia is considered to be neuroprotective after severe brain damage. We examined the effects of hypothermic culture on the production of pro- and anti-inflammatory cytokines and NO in ex vivo microglia that were derived from mice with hypoxic-ischemic (HI) brain injury, through the stimulation of toll-like receptors (TLRs) that play significant roles in the pathological processes underlying a sterile central nervous system injury. MATERIAL AND METHODS: Two-day-old mice underwent the right common carotid artery ligation followed by 6% oxygen for 30 min, and thereafter were placed at 37 degrees C for 24 h, after which microglia were isolated and then cultured with TLR2 and TLR4 agonists at 33 degrees C and 37 degrees C. Cytokine and NO levels in culture supernatants were measured. RESULTS: Compared with 37 degrees C, hypothermia (33 degrees C) reduced the production of tumour necrosis factor-alpha (TNF-alpha: a pro-inflammatory cytokine) at 6 h and interleukin-10 (IL-10: an anti-inflammatory cytokine) and NO at 48 h. CONCLUSIONS: In TLR-activated microglia that were derived from mice with HI brain injury, hypothermia reduced the production of TNF-alpha, IL-10, and NO temporally, a clinically relevant finding suggesting that neuroprotection conferred by therapeutic hypothermia is related to attenuation of early-phase and late-phase inflammatory factors as well as that of late-phase anti-inflammatory factor(s) released from microglia. PMID- 25118901 TI - Monitoring of very long-chain fatty acids levels in X-linked adrenoleukodystrophy, treated with haematopoietic stem cell transplantation and Lorenzo's Oil. AB - X-linked adrenoleukodystrophy is a rare, neurodegenerative peroxisomal disorder connected with mutation in the ABCD1 gene, causing impairment of the peroxisomal beta-oxidation process and in consequence, accumulation of very long-chain fatty acids (VLCFA) in blood and tissues. In this study we present serum very long chain fatty acids levels during clinical course in an X-linked adrenoleukodystrophy patient after haematopoietic stem cell transplantation (HSCT) and on Lorenzo's Oil in a 11 years' period. The patient was diagnosed at the age of 8 months by family screening. The administration of LO was started at 2 years of age. HSCT from a family donor was performed twice. VLCFA serum levels were detected by the GC method. Chimaerism subsequent to HSCT was also analyzed. Increasing very long-chain fatty acids levels correlate with a decreasing chimaerism level after haematopoietic stem cell transplantation. The sequential monitoring of very long-chain fatty acids serum levels is important and useful for assessment of engraftment, graft failure or rejection. PMID- 25118902 TI - Involvement of D1/D2 dopamine antagonists upon open-arms exploratory behaviours induced by intra-nucleus accumbens shell administration of N-methyl-D-aspartate. AB - Glutamatergic system stimulation in some parts of the brain may affect anxiety related behaviours, aversive learning and memory. This system retains many interactions with dopaminergic neurotransmission. We have studied the effect of nucleus accumbens (NAc) shell glutamatergic system activation on anxiety-related behaviours as well as aversive learning and memory in adult male Wistar rats using the N-methyl-D-aspartate (NMDA) receptor agonist, NMDA. Furthermore, the possible involvement of the NAc shell dopamine D1 and D2 receptors upon NMDA induced effects was evaluated. The elevated plus-maze task was used to assess the drugs' concomitant effects on anxiety, learning and memory in rats. All drugs were delivered into the NAc shell via bilaterally implanted indwelling cannulae. The NMDA-induced anxiolytic-like behaviours upon retest could possibly be attributed to the further avoidance acquisition impairments. Moreover, the inhibition of dopaminergic system using SCH 23390 and sulpiride induced an anxiolytic-like response and impaired the aversive memory acquisition during retest. However, the concurrent intra-NAc shell microinjection of the subthreshold dose of SCH 23390 and sulpiride (0.125 ug/rat) reversed the anxiolytic-like effect and blocked the aversive memory impairment induced by intra-NAc shell NMDA. Our results suggest a modulatory role of the NAc shell dopaminergic system on NMDA-induced effects in the aversive memory. PMID- 25118903 TI - Neuroprotective effect of rotigotine against complex I inhibitors, MPP+ and rotenone, in primary mesencephalic cell culture. AB - INTRODUCTION: Dopamine agonists are suggested to be more efficacious in treating Parkinson's disease (PD) as they have neuroprotective properties in addition to their receptor-related actions. AIM OF THE STUDY: The present study was designed to investigate the neuroprotective effects of rotigotine, a D3/D2/D1 dopamine receptor agonist, against the two powerful complex I inhibitors, 1-methyl-4 phenylpyridinium (MPP+) and rotenone, in primary mesencephalic cell culture relevant to PD. MATERIAL AND METHODS: Primary mesencephalic cell cultures were prepared from embryonic mouse mesencephala at gestation day 14. Three sets of cultures were treated with rotigotine alone, rotigotine and MPP+, and rotigotine and rotenone to investigate the effect of rotigotine on the survival of dopaminergic neurons against age-, MPP+- and rotenone-induced cell death. At the end of each treatment, cultures were fixed and stained immunohistochemically against tyrosine hydroxylase (TH). The effect of rotigotine against rotenone induced reactive oxygen species (ROS) production was measured using CH-H2DCFDA fluorescence dye. RESULTS: Rotigotine alone did not influence the survival of tyrosine hydroxylase immunoreactive (THir) neurons except at 10 uM, it significantly decreased the number of THir neurons by 40% compared to untreated controls. Treatment of cultures with 0.01 uM rotigotine rescued 10% of THir neurons against MPP+-induced cell death. Rotigotine was also found to significantly rescue 20% of THir neurons at 0.01 uM of rotenone-treated cultures. Using of CH-H2DCFDA fluorescence dye, it was found that rotigotine significantly attenuated ROS production compared to rotenone-treated cultures. CONCLUSIONS: Rotigotine provides minor protection against MPP+ and rescues a significant number of THir neurons against rotenone in primary mesencephalic cell cultures relevant to PD. PMID- 25118904 TI - Primary angiitis of the central nervous system: a study of histopathological patterns and review of the literature. AB - Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis of unknown aetiology. Multifaceted clinical manifestations, non specific MRI findings, a broad range of differential diagnoses and diverse pathological appearances prove to be a diagnostic challenge. However, a prompt diagnosis and aggressive treatment are crucial to avoid permanent damage. Hence, we present the clinico-pathological spectrum of this entity and highlight the limitations of currently available diagnostic modalities. We describe in detail the histopathological findings of eight cases of PACNS diagnosed at the Department of Pathology, AIIMS, over a period of eight years. Eight cases of PACNS were identified during this period. Five cases (62.5%) showed features of granulomatous vasculitis, two (25%) showed lymphocytic vasculitis and one case (12.5%) showed a predominantly necrotizing pattern of vasculitis. Diagnosis of PACNS is a challenge and requires a high index of clinical suspicion. Appropriate work-up to exclude other conditions is mandatory. Brain biopsy is useful in making the diagnosis and ruling out mimicking conditions. PMID- 25118905 TI - Dendritic and spinal alterations of neurons from Edinger-Westphal nucleus in Alzheimer's disease. AB - Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder, causing a progressive decline of intellectual faculties, impairment of behavior and social performance, and impairment of speech eloquence, associated with various neurological manifestations based on a variable neuropathological background. Edinger-Westphal nucleus is a selective target of Alzheimer pathology early in the course of the disease. We attempted to determine the morphological alterations of the dendrites and the dendritic spines in Edinger-Westphal nucleus of 7 cases that fulfilled the diagnostic criteria for Alzheimer's disease. For the histological study, we applied (a) routine neuropathological techniques and (b) rapid Golgi method. We proceeded to 3D neuronal reconstruction for the estimation of dendritic and spinal changes in Alzheimer's disease. The morphological and morphometric analysis revealed a substantial neuronal loss and synaptic alterations in Edinger-Westphal nucleus in all the cases of Alzheimer's disease. Distal dendritic branches are prominently affected. The neuronal loss and alteration of the spines in Edinger-Westphal nucleus in Alzheimer's disease may be related to the exaggerated pupillary reaction to cholinergic antagonists. Furthermore, the vulnerability of distal branches to Alzheimer's disease might be related to neuroplasticity impairment. PMID- 25118906 TI - Iron-induced fibrin formation may explain vascular pathology in Alzheimer's disease. PMID- 25118907 TI - A genomewide study of body mass index and its genetic correlation with thromboembolic risk. Results from the GAIT project. AB - Thrombosis and obesity are complex epidemiologically associated diseases. The mechanism of this association is not yet understood. It was the objective of this study to identify genetic components of body mass index (BMI) and their possible role in the risk of thromboembolic disease. With the self-reported BMI of 397 individuals from 21 extended families enrolled in the GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project, we estimated the heritability of BMI and the genetic correlation with the risk of thrombosis. Subjects were genotyped for an autosomal genome-wide scan with 363 highly-informative DNA markers. Univariate and bivariate multipoint linkage analyses were performed. The heritability for BMI was 0.31 (p=2.9*10-5). Thromboembolic disease (including venous and arterial) and BMI had a significant genetic correlation (rhoG=0.54, p=0.005). Two linkage signals for BMI were obtained, one at 13q34 (LOD=3.36, p=0.0004) and other at 2q34, highly suggestive of linkage (LOD=1.95). Bivariate linkage analysis with BMI and thrombosis risk also showed a significant signal at 13q34 (LOD=3), indicating that this locus influences at the same time normal variation in the BMI phenotype as well as susceptibility to thrombosis. In conclusion, BMI and thrombosis are genetically correlated. The locus 13q34, which showed pleiotropy with both phenotypes, contains two candidate genes, which may explain our linkage pleiotropic signal and deserve further investigation as possible risk factors for obesity and thrombosis. PMID- 25118908 TI - Targeting Plasmodium falciparum transmission with primaquine: same efficacy, improved safety with a lower dose? AB - Malaria transmission is declining worldwide, leading to a growing interest in strategies to reach elimination and eradication. Insecticide and drug resistance threaten these efforts, driving an interest in the use of gametocytocidal drugs to curb the spread of artemisinin resistance and accelerate the path to malaria elimination. Primaquine is the only marketed drug that can kill mature Plasmodium falciparum gametocytes, which can otherwise contribute to ongoing transmission for long periods of time. While primaquine has been widely used in Asia and the Americas, African countries have little experience with this drug and are reluctant to use primaquine due to a fear of hemolytic side effects. We discuss the underlying knowledge base and motivation to use primaquine as a P. falciparum transmission blocker, revealing that while primaquine implementation can benefit from further study, there remains an overall need for improved transmission blocking drugs. PMID- 25118910 TI - A mathematical model evaluating the timing of early diagnostic testing in HIV exposed infants in South Africa. AB - BACKGROUND: Antiretroviral therapy is often initiated too late to impact early HIV-related infant mortality. Earlier treatment requires an earlier diagnosis, and the currently recommended 6-week HIV polymerase chain reaction (PCR) test needs reconsideration. This study aims to identify (1) optimal testing intervals to maximize the number of perinatal HIV infections diagnosed and (2) programmatic issues that impact diagnosis. METHODS: A mathematical model was developed to simulate antiretroviral prophylaxis uptake and health outcomes in 240,000 HIV exposed South African infants. The model considered routine early testing with 1 PCR (at birth, 6, 10, or 14 weeks of age) and with 2 PCR tests (at birth and at 6, 10, or 14 weeks of age). RESULTS: A single 6-week test would diagnose the same number of perinatal HIV infections as birth testing (P = 0.92) but fewer infections than a 10-week test (P < 0.01). Ten-week testing identifies the highest number of perinatally infected infants (P < 0.01 compared with a single test at all other ages) but does not save additional life years compared with birth testing (P = 0.27). Performing 2 PCR tests (at birth and 10 weeks) would identify the highest number of perinatal infections (P < 0.01 versus a second 6- or 14-week test). However, 25% of perinatal HIV infections would remain undiagnosed, largely because of failure to return PCR test results to caregivers. CONCLUSIONS: Six weeks may no longer be the optimal age to diagnose perinatal HIV infections. Two early PCR tests (at birth and 10 weeks) would likely be the ideal diagnostic algorithm, but must be coupled with improved program coverage. PMID- 25118911 TI - Differential co-expression analysis of rheumatoid arthritis with microarray data. AB - The aim of the present study was to investigate the underlying molecular mechanisms of rheumatoid arthritis (RA) using microarray expression profiles from osteoarthritis and RA patients, to improve diagnosis and treatment strategies for the condition. The gene expression profile of GSE27390 was downloaded from Gene Expression Omnibus, including 19 samples from patients with RA (n=9) or osteoarthritis (n=10). Firstly, the differentially expressed genes (DEGs) were obtained with the thresholds of |logFC|>1.0 and P<0.05, using the t-test method in LIMMA package. Then, differentially co-expressed genes (DCGs) and differentially co-expressed links (DCLs) were screened with q<0.25 by the differential coexpression analysis and differential regulation analysis of gene expression microarray data package. Secondly, pathway enrichment analysis for DCGs was performed by the Database for Annotation, Visualization and Integrated Discovery and the DCLs associated with RA were selected by comparing the obtained DCLs with known transcription factor (TF)-targets in the TRANSFAC database. Finally, the obtained TFs were mapped to the known TF-targets to construct the network using cytoscape software. A total of 1755 DEGs, 457 DCGs and 101988 DCLs were achieved and there were 20 TFs in the obtained six TF-target relations (STAT3-TNF, PBX1-PLAU, SOCS3-STAT3, GATA1-ETS2, ETS1-ICAM4 and CEBPE-GATA1) and 457 DCGs. A number of TF-target relations in the constructed network were not within DCLs when the TF and target gene were DCGs. The identified TFs may have an important role in the pathogenesis of RA and have the potential to be used as biomarkers for the development of novel diagnostic and therapeutic strategies for RA. PMID- 25118912 TI - The third issue of 2014. Editorial. PMID- 25118913 TI - Intervention program efficacy for spelling difficulties. AB - OBJECTIVE: To develop an intervention procedure for spelling difficulties and to verify the effectiveness of the intervention program in students with lower spelling performance. METHOD: We developed an intervention program for spelling difficulties, according to the semiology of the errors. The program consisted of three modules totaling 16 sessions. The study included 40 students of the third to fifth grade of public elementary education of the city of Marilia (SP), of both genders, in aged of eight to 12 years old, being distributed in the following groups: GI (20 students with lower spelling performance) and GII (20 students with higher spelling performance). In situation of pre and post-testing, all groups were submitted to the Pro-Orthography. RESULTS: The results statistically analyzed showed that, in general, all groups had average of right that has higher in post-testing, reducing the types of errors second semiologycal classification, mainly related to natural spelling errors. However, the results also showed that the groups submitted to the intervention program showed better performance on spelling tests in relation to not submitted. CONCLUSION: The intervention program developed was effective once the groups submitted showed better performance on spelling tests in relation to not submitted. Therefore, the intervention program can help professionals in the Health and Education to minimize the problems related to spelling, giving students an intervention that is effective for the development of the spelling knowledge. PMID- 25118914 TI - The lexical development of children with hearing impairment and associated factors. AB - PURPOSE: This study aimed at analyzing the association between the lexical development of children with hearing impairment and their psychosocial and socioeconomic characteristics and medical history. METHODS: An analytic transversal study was conducted in an Auditive Health Attention Service. One hundred and ten children from 6 to 10 years old using hearing aids and presenting hearing loss that ranged from light to deep levels were evaluated. All children were subjected to oral, written language and auditory perception tests. Parents answered a structured questionnaire to collect data from their medical history and socioeconomic status, and questionnaires about the features of the family environment and psychosocial characteristics. Multivariate analysis was performed by logistic regression, being the initial model composed by variables with p<0,20 in the univariate analysis. In the final model, we adopted a significance level of 5%. RESULTS: The final model of the multivariate analysis showed an association between the performance on the vocabulary test and the results of phonemic discrimination test (OR=0.81; 95%CI 0.73-0.89). CONCLUSION: The results show the importance of stimulating the auditory processing, particularly the phonemic discrimination skill, throughout the rehabilitation process of children with hearing impairment. This stimulation can enhance lexical development and minimize the metalanguage and learning difficulties often observed in these children. PMID- 25118916 TI - Comparing the results of DAADD and ABC of children included in autism spectrum disorders. AB - PURPOSE: To verify if there are characteristic behaviors of the different diagnosis included in the autism spectrum according to the Differential Assessment of Autism and Other Developmental Disorders (DAADD) and to the Autism Behavior Checklist (ABC). METHOD: Participants were 45 individuals and their respective speech-language therapists. All therapists are graduate students working with the children for at least 1 year. This time was considered sufficient to the therapists to have the information required by the DAADD questionnaire. It is comprised by 3 protocols specifically designed to children with 2 to 4 years, 4 to 6 years and 6 to 8 years, the same criteria used to separate the research groups, G1, G2 and G3, respectively. Data referring to the ABC were retrieved from the subject's files at the Laboratorio de Investigacao Fonoaudiologica nos Disturbios do Espectro do Autismo (Research Laboratory on Language Disorders in the Autism Spectrum) of the School of Medicine, Universidade de Sao Paulo, where it is routinely applied during the annual assessment. RESULTS: Answers to the different areas of DAADD are similar to the different areas of ABC. These data show data the diagnosis by DAADD is easier in older children. Although there is no significant difference, the large occurrence of Rett's syndrome diagnosis according to the DAADD was associated to higher risk for autism according to the ABC in G1. With increasing age this tendency decreases and either in G2 and G3 Autism is the most frequent diagnosis. CONCLUSION: Although the results of both questionnaires tend to agree more with increasing age, the DAADD is more sensitive in the different ages while the ABC if more specific only to older children. PMID- 25118915 TI - Mean length utterance in Brazilian children: a comparative study between Down syndrome, specific language impairment, and typical language development. AB - PURPOSE: To describe the linguistic performance of Brazilian Portuguese-speaking children with Down syndrome by analyzing their Mean Length Utterance; to compare their performance to that of children with Specific Language Impairment and Typical Development; and to verify whether children with Down syndrome present developmental language delay or disorder. METHOD: Participants were 25 children with Down syndrome (Research Group), matched by mental age to a Control Group of typically developing children, and to a Control Group of children with Specific Language Impairment. Participants were divided into subgroups, according to age range (three, four and five years). Speech samples were collected for the Research Group, and the Mean Length Utterance was analyzed for morphemes and words. RESULTS: Differences were observed between the performance of the Research Group and both Control Groups, and the former presented inferior Mean Length Utterance values for all age ranges, characterizing a delay in grammar and general language development. CONCLUSION: The description of the linguistic abilities of Brazilian Portuguese-speaking children with Down syndrome indicated important grammatical deficits, especially regarding the use of functional words. PMID- 25118917 TI - Global developmental abilities of cochlear implanted children with spastic cerebral palsy: two experimental groups. AB - PURPOSE: To analyze gross motor, fine motor-adaptive, language, social function performance, and communicative behaviors among cochlear-implanted children with spastic cerebral palsy (CP) and children with CP without hearing loss (HL) and to compare them with children with normal development. METHODS: Prospective cross sectional study involving 12 children with mean age of 63 months, distributed into two experimental groups: G1-4 children with CP and cochlear implant (CI) users and G2-4 children with CP without HL. A third group (G3) was the control group with four typically developing children. In the experimental groups, six children were classified in level II and two in level IV, using the Gross Motor Function Classification System. We used the Denver Developmental Screening Test II and the Communicative Behavior Observation (CBO). RESULTS: G3 showed better performance than G1 and G2 in all evaluations. G2 showed better results than G1 in language, communication, personal-social, and fine motor-adaptive areas, except in the gross motor area. Aspects of language and communicative behaviors were lower in both experimental groups, especially in G1. Skills related to personal-social area showed no differences among the groups. CONCLUSION: Motor impairment of G1 and G2 and HL in G1 affected the development in the assessed areas, but these factors did not restrict personal-social development. Children with CP did not achieve high development in social function; however, the difference with relation to G3 was not statically significant. The CI provided a channel for oral language reception and social interaction, which has a key role in determining the quality of life. PMID- 25118918 TI - Otoacoustic emissions and biomarkers of oxidative stress in students of a tobacco producing region. AB - PURPOSE: To verify the association between the amplitude of distortion-product otoacoustic emissions (DPOAE) and biomarkers of oxidative stress (OS) in resident students of the tobacco-producing region. METHODS: Participated in the study group (SG) 21 normal-hearing students from the tobacco-producing region, and in the control group (CG) 25 normal-hearing students who did not live in the countryside. The auditory system was assessed by DPOAE and the following biomarkers: dichlorofluorescein diacetate (DCFH-DA) and micronucleus test (MN). RESULTS: Both groups showed DPOAE present in both ears. Significant difference was detected between groups--in the right ear in the frequency of 4.000 Hz and in the left ear in the frequency of 2.000 Hz--with the mean amplitude of the DPOAE of the SG lower than the one found in the CG. Considering both ears, the SG presented lower mean across all frequencies and it was found a significant difference in the frequencies of 2.000 and 4.000 Hz. The overall mean of DPOAE, by ear, no significant differences were observed. In relation to the rate of production of free radicals, the mean of the SG was significantly higher than that of the mean of the CG. For the frequency of abnormal cells in the MN test, the mean of the SG was also considerate significantly higher than the mean of the CG. CONCLUSION: The SG showed a lower response level of DPOAE at all frequencies and high levels of biomarkers of EO, however there was no association between assessments. PMID- 25118919 TI - Correlation of the findings of auditory steady-state evoked potential and of behavioral hearing assessment in infants with sensorineural hearing loss. AB - PURPOSE: To correlate the findings of an open-field audiometry with the thresholds of steady-state auditory-evoked potentials (SSAEPs) found in infants of up to 6 months of age with sensorineural hearing loss. METHODS: This study included 19 infants with sensorineural hearing loss (8 males and 11 females), with minimum age of 2 months and maximum age of 6 months. The SSAEPs were assessed at 500 and 2000 Hz, and the audiometry was performed in open field through observation of behavioral responses to sound stimuli, at the same frequencies. RESULTS: We observed a significant correlation between the findings of both tests conducted at 500 and 2000 Hz, with p-values of 0.002 and 0.013, respectively. There was no statistical difference between ears (p=0.532) and genders (p=0.615). CONCLUSION: We conclude that there was a significant correlation between the SSAEP thresholds and the findings of the open-field audiometry. Therefore, we can affirm that the SSAEPs are a viable examination, able to predict the degree and configuration of hearing loss in infants of up to 6 months of age, and that they can be included in the clinical routine of hearing assessments conducted in children. PMID- 25118920 TI - Association between pharyngeal residue and posterior oral spillage with penetration and aspiration in stroke. AB - PURPOSE: This study aimed at showing association between the posterior oral spillage and pharyngeal residue with tracheal aspiration and/or laryngeal penetration in stroke. METHODS: Clinical cross-sectional retrospective multicenter study. The study included 63 videofluoroscopic tests of post-ischemic stroke individuals and oropharyngeal dysphagia data of the three reference centers providing care for patients with dysphagia (43 men and 20 women; age range: from 40 to 90 years). These individuals were divided into two groups. Group I consisted of 35 participants with the presence of penetration and/or laryngotracheal aspiration, and Group II consisted of 28 individuals with no penetration and/or aspiration. Videofluoroscopic swallowing test results were analyzed to divide the groups, and the presence of posterior oral spillage and pharyngeal residue was observed. RESULTS: No association was found between the groups with posterior oral spillage (chi2=1.65; p=0.30; phi2=0.02), but there was statistical difference for the association between pharyngeal residue (chi2=12.86; p=0.003; phi2=0.20) and the groups. CONCLUSION: There is an association between pharyngeal residue and penetration with tracheal aspiration in post-stroke individuals. PMID- 25118921 TI - Evaluation of the force applied by the tongue and lip on the maxillary central incisor tooth. AB - PURPOSE: To describe the development and testing of a system that measures forces exerted by the tongue and upper lip on a tooth during rest and during swallowing. METHODS: Twenty-eight subjects, aged 19-31 years (mean: 23.2 years) were submitted to measurement of forces exerted by the upper lip and tongue on the maxillary right central incisor tooth. Flexiforce resistive sensors were fixed on the labial and lingual surfaces of the tooth. They were connected to an amplifier circuit and a data acquisition board for processing and transmitting information to a computer. RESULTS: At rest, the tongue force on the tooth was 0.00+/-0.00 N and the lip force on tooth was 0.02+/-0.02 N. The difference between them was significant. During swallowing, the values were 0.31+/-0.38 N and 0.15+/-0.14 N, for the tongue and lip, respectively. This difference was not significant. CONCLUSION: At rest, the lip exerts a larger force than the tongue on the maxillary right central incisor tooth. During swallowing, there was no difference between lip and tongue force on the tooth. PMID- 25118922 TI - National Policy on Health Care Hearing: an evaluative study from covering services and diagnostic procedures. AB - PURPOSE: To evaluate the National Policy on Hearing Health Care (PNASA) based on the coverage of specialized services and diagnostic procedures in hearing health care in Brazil. METHODS: This is an evaluation study focused on the coverage of specialized services that offer moderate- and high-complexity diagnostic procedures by region and in Brazil as a whole. We analyzed the data for the period of 2004-2011 collected from the Unified Health System's Informatics Department database (DATASUS), under the link "Information on health" and tabulated using the software Tabwin. While collecting data from this platform, we selected "procedures for diagnostic purposes", and the selected way of organization was "diagnoses in otorhinolaryngology/audiology" of moderate and high complexity. We estimated coverage and evolution of the number of procedures according to the country's five geographic macroregions. RESULTS: We identified an increase of 113% in service coverage and of 61% in the quantity of moderate- and high-complexity hearing health diagnostic procedures throughout the country. The northern region had an increase of 78% in the number of procedures, higher than all other regions. However, a proportionally larger number of procedures were performed in the southeast. We identified a significant increase in the number of examinations of otoacoustic emissions (OAE) for hearing triage, transient-evoked OAE and distortion product, as well as of diagnostic reassessments of hearing loss in patients older than 3 years. CONCLUSION: There has been an increase in services and actions in hearing health care in Brazil since PNASA was implemented, but regional inequalities in the distribution of these services still persist. PMID- 25118923 TI - Tongue contour for /s/ and /?/ in children with speech sound disorder. AB - PURPOSE: To describe the tongue shape for /s/ and /?/ sounds in three different groups of children with and without speech sound disorder. METHODS: The six participants were divided into three groups: Group 1--two typically developing children, Group 2--two children with speech sound disorder presenting any other phonological processes but not the ones involving the production of the /?/ and Group 3--two children with speech sound disorder presenting any phonological processes associated to the presence of the phonological process of palatal fronting (these two children produced /?/ as /s/) aged between 5 and 8 years old, all speakers of Brazilian Portuguese. The data were the words /'?avi/ (key) and /'sapu/ (frog). Tongue contour was individually traced for the five productions of each target word. RESULTS: The analysis of the tongue contour pointed to evidences that both /s/ and /?/ were produced using distinct tongue contours for G1 and G2. The production of these two groups was more stable than G3. The tongue contour for /s/ and /?/ from the children in G3 was similar, indicating that their production was undifferentiated. CONCLUSION: The use of the ultrasound applied to the speech analysis was effective to confirm the perceptual analysis of the sound made by the speech-language pathologist. PMID- 25118924 TI - Cross-cultural adaptation of the Italian version of the Voice Activity Participation Profile. AB - The Vocal Activity Participation Profile (VAPP), originally developed in English, is a self-assessment tool used to measure individuals' voice activity limitation and participation restriction. Based on the fact that the cultural/linguistic adaptation is an essential step of validating a protocol in another language, the purpose was to linguistically and culturally adapt the VAPP into Italian. The adaptation was performed in accordance to the Scientific Advisory Committee of the Medical Outcomes Trust. The translation was performed by one bilingual speech language pathologist and by one bilingual interpreter, who knew about the purpose of this project. A bilingual English teacher, who had not participated in the previous step, performed the back translation. A committee composed by three speech-language pathologists specialized in voice and one laryngologist compared the forward and backward translations, to assess for any discrepancies. A final version was produced and called Profilo di Attivita e Partecipazione Vocale (PAPV). A "not applicable" option was included to each item and was administered to 17 individuals with voice problems, six males and 11 females, aged between 21 to 55 years. All items were relevant, as no patients chose the "not applicable" option. However, four individuals, who had a lower educational level, did not fully understand the instructions of the opening statement. Therefore, the questionnaire was further reviewed and adjusted to clarify the information. Otherwise, no items were changed and/or deleted. The PAPV kept the same structure as the original version. The cultural equivalence of the Italian VAPP was demonstrated and entitled PAPV, whose validation is currently in process. PMID- 25118925 TI - Speech language therapy for cancer patients and new tendencies. PMID- 25118926 TI - Non-apoptotic functions of caspase-7 during osteogenesis. AB - Caspase-3 and -7 are generally known for their central role in the execution of apoptosis. However, their function is not limited to apoptosis and under specific conditions activation has been linked to proliferation or differentiation of specialised cell types. In the present study, we followed the localisation of the activated form of caspase-7 during intramembranous (alveolar and mandibular bones) and endochondral (long bones of limbs) ossification in mice. In both bone types, the activated form of caspase-7 was detected from the beginning of ossification during embryonic development and persisted postnatally. The bone status was investigated by microCT in both wild-type and caspase-7-deficient adult mice. Intramembranous bone in mutant mice displayed a statistically significant decrease in volume while the mineral density was not altered. Conversely, endochondral bone showed constant volume but a significant decrease in mineral density in caspase-7 knock-out mice. Cleaved caspase-7 was present in a number of cells that did not show signs of apoptosis. PCR array analysis of the mandibular bone of caspase-7-deficient versus wild-type mice pointed to a significant decrease in mRNA levels for Msx1 and Smad1 in early bone formation. These observations might explain the decrease in the alveolar bone volume of adult knock-out mice. In conclusion, this study is the first to report a non apoptotic function of caspase-7 in osteogenesis and also demonstrates further specificities in endochondral versus intramembranous ossification. PMID- 25118927 TI - Autophagy promotes paclitaxel resistance of cervical cancer cells: involvement of Warburg effect activated hypoxia-induced factor 1-alpha-mediated signaling. AB - Paclitaxel is one of the most effective chemotherapy drugs for advanced cervical cancer. However, acquired resistance of paclitaxel represents a major barrier to successful anticancer treatment. In this study, paclitaxel-resistant HeLa sublines (HeLa-R cell lines) were established by continuous exposure and increased autophagy level was observed in HeLa-R cells. 3-Methyladenine or ATG7 siRNA, autophagy inhibitors, could restore sensitivity of HeLa-R cells to paclitaxel compared with parental HeLa cells. To determine the underlying molecular mechanism, differentially expressed proteins between HeLa and HeLa-R cells were identified by two-dimensional gel electrophoresis coupled with electrospray ionization quadrupole time-of-flight MS/MS. We found glycolysis associated proteins were upregulated in HeLa-R cell lines. Inhibition of glycolysis by 2-deoxy-D-glucose or koningic acid could decrease autophagy and enhance sensitivity of HeLa-R cells to paclitaxel. Moreover, glycolysis could activate HIF1-alpha. Downregulation of HIF1-alpha by specific siRNA could decrease autophagy and resensitize HeLa-R cells to paclitaxel. Taken together, a possible Warburg effect activated HIF1-alpha-mediated signaling-induced autophagic pathway is proposed, which may provide new insight into paclitaxel chemoresistance. PMID- 25118928 TI - The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling. AB - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been associated with Parkinson's disease, and its inhibition opens potential new therapeutic options. Among the drug inhibitors of both wild-type and mutant LRRK2 forms is the 2-arylmethyloxy-5-subtitutent-N-arylbenzamide GSK257815A. Using the well established dopaminergic cell culture model SH-SY5Y, we have investigated the effects of GSK2578215A on crucial neurodegenerative features such as mitochondrial dynamics and autophagy. GSK2578215A induces mitochondrial fragmentation of an early step preceding autophagy. This increase in autophagosome results from inhibition of fusion rather than increases in synthesis. The observed effects were shared with LRRK2-IN-1, a well-described, structurally distinct kinase inhibitor compound or when knocking down LRRK2 expression using siRNA. Studies using the drug mitochondrial division inhibitor 1 indicated that translocation of the dynamin-related protein-1 has a relevant role in this process. In addition, autophagic inhibitors revealed the participation of autophagy as a cytoprotective response by removing damaged mitochondria. GSK2578215A induced oxidative stress as evidenced by the accumulation of 4 hydroxy-2-nonenal in SH-SY5Y cells. The mitochondrial-targeted reactive oxygen species scavenger MitoQ positioned these species as second messengers between mitochondrial morphologic alterations and autophagy. Altogether, our results demonstrated the relevance of LRRK2 in mitochondrial-activated pathways mediating in autophagy and cell fate, crucial features in neurodegenerative diseases. PMID- 25118929 TI - Stabilization of apoptotic cells: generation of zombie cells. AB - Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn(2+) (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy. PMID- 25118930 TI - Release and activity of histone in diseases. AB - Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription. Besides intranuclear functions, histones act as damage-associated molecular pattern molecules when they are released into the extracellular space. Administration of exogenous histones to animals leads to systemic inflammatory and toxic responses through activating Toll-like receptors and inflammasome pathways. Anti-histone treatment (e.g., neutralizing antibodies, activated protein C, recombinant thrombomodulin, and heparin) protect mice against lethal endotoxemia, sepsis, ischemia/reperfusion injury, trauma, pancreatitis, peritonitis, stroke, coagulation, and thrombosis. In addition, elevated serum histone and nucleosome levels have been implicated in multiple pathophysiological processes and progression of diseases including autoimmune diseases, inflammatory diseases, and cancer. Therefore, extracellular histones could serve as biomarkers and novel therapeutic targets in human diseases. PMID- 25118931 TI - Improving the therapeutic potential of endostatin by fusing it with the BAX BH3 death domain. AB - Endostatin (ES) inhibits angiogenesis, reducing tumor growth in animal models. However, it has low therapeutic effect in human clinical trials. BAX is a member of the BCL-2 family of proteins; its proapoptotic (BH3) domain interacts with other members of the family in the cytoplasm, to induce apoptosis. Here, we fused the BAX BH3 domain with murine ES, to enhance ES potency. Endothelial cells specifically internalize the fusion protein ES-BAX. The presence of the BAX domain enhances endothelial cell death by apoptosis by 1.8-fold and diminishes microvessel outgrowth in the rat aortic ring assay by 6.5-fold. Daily injections of 15 MUg of ES-BAX/g in tumor-bearing mice reduce tumor weight by 86.9% as compared with ES-treated animals. Co-immunoprecipitation assays confirmed that ES BAX interacts with members of the BCL-2 family. Also, ES interacts with BCL-2, BCL-XL, and BAK in endothelial cell lysates, suggesting a potential new mechanism for the apoptosis induction by ES. The superiority of the ES-BAX antiangiogenic effect indicates that this fusion protein could be a promising therapeutic alternative to treat cancer. PMID- 25118932 TI - Cholesterol oxidase from Bordetella species promotes irreversible cell apoptosis in lung adenocarcinoma by cholesterol oxidation. AB - Cholesterol oxidase (COD), an enzyme catalyzing the oxidation of cholesterol, has been applied to track the distribution of membrane cholesterol. Little investigations about the effect of COD on tumor cells have been performed. In the present study, we provided evidence that COD from Bordetella species (COD-B), induced apoptosis of lung cancer cells in vitro and in vivo. COD-B treatment inhibited Akt and ERK1/2 phosphorylation in dose- and time-dependent manner, which was not reversed and was even aggravated by cholesterol addition. Further investigation indicated that COD-B treatment promoted the generation of reactive oxygen species (ROS) and that cholesterol addition further elevated ROS levels. Moreover, COD-B treatment resulted in JNK and p38 phosphorylation, downregulation of Bcl-2, upregulation of Bax, activated caspase-3 and cytochrome C release, which likely responded to freshly produced hydrogen peroxide that accompanied cholesterol oxidation. Catalase pretreatment could only partially prevent COD-B induced events, suggesting that catalase inhibited H2O2-induced signal transduction but had little effect on signal pathways involved in cholesterol depletion. Our results demonstrated that COD-B led to irreversible cell apoptosis by decreasing cholesterol content and increasing ROS level. In addition, COD-B may be a promising candidate for a novel anti-tumor therapy. PMID- 25118933 TI - The protease Omi regulates mitochondrial biogenesis through the GSK3beta/PGC 1alpha pathway. AB - Loss of the mitochondrial protease activity of Omi causes mitochondrial dysfunction, neurodegeneration with parkinsonian features and premature death in mnd2 (motor neuron degeneration 2) mice. However, the detailed mechanisms underlying this pathology remain largely unknown. Here, we report that Omi participates in the process of mitochondrial biogenesis, which has been linked to several neurodegenerative diseases. The mitochondrial biogenesis is deficit in mnd2 mice, evidenced by severe decreases of mitochondrial components, mitochondrial DNA and mitochondrial density. Omi cleaves glycogen synthase kinase 3beta (GSK3beta), a kinase promoting PPARgamma coactivator-1alpha (PGC-1alpha) degradation, to regulate PGC-1alpha, a factor important for the mitochondrial biogenesis. In mnd2 mice, GSK3beta abundance is increased and PGC-1alpha abundance is decreased significantly. Inhibition of GSK3beta by SB216763 or overexpression of PGC-1alpha can restore mitochondrial biogenesis in mnd2 mice or Omi-knockdown N2a cells. Furthermore, there is a significant improvement of the movement ability of mnd2 mice after SB216763 treatment. Thus, our study identified Omi as a novel regulator of mitochondrial biogenesis, involving in Omi protease-deficient-induced neurodegeneration. PMID- 25118934 TI - Specific antibody binding to the APP672-699 region shifts APP processing from alpha- to beta-cleavage. AB - Alzheimer's disease (AD), a progressive neurodegenerative disorder that is the most common cause of dementia in the elderly, is characterized by the accumulation of amyloid-beta (Abeta) plaques and neurofibrillary tangles, as well as a progressive loss of synapses and neurons in the brain. The major pertinacious component of amyloid plaques is Abeta, a variably sized peptide derived from the integral membrane protein amyloid precursor protein (APP). The Abeta region of APP locates partly within its ecto- and trans-membrane domains. APP is cleaved by three proteases, designated as alpha-, beta-, and gamma secretases. Processing by beta- and gamma-secretase cleaves the N- and C-terminal ends of the Abeta region, respectively, releasing Abeta, whereas alpha-secretase cleaves within the Abeta sequence, releasing soluble APPalpha (sAPPalpha). The gamma-secretase cleaves at several adjacent sites to yield Abeta species containing 39-43 amino acid residues. Both alpha- and beta-cleavage sites of human wild-type APP are located in APP672-699 region (ectodomain of beta-C terminal fragment, ED-beta-CTF or ED-C99). Therefore, the amino acid residues within or near this region are definitely pivotal for human wild-type APP function and processing. Here, we report that one ED-C99-specific monoclonal antibody (mAbED-C99) blocks human wild-type APP endocytosis and shifts its processing from alpha- to beta-cleavage, as evidenced by elevated accumulation of cell surface full-length APP and beta-CTF together with reduced sAPPalpha and alpha-CTF levels. Moreover, mAbED-C99 enhances the interactions of APP with cholesterol. Consistently, intracerebroventricular injection of mAbED-C99 to human wild-type APP transgenic mice markedly increases membrane-associated beta CTF. All these findings suggest that APP672-699 region is critical for human wild type APP processing and may provide new clues for the pathogenesis of sporadic AD. PMID- 25118937 TI - Depletion of intermediate filament protein Nestin, a target of microRNA-940, suppresses tumorigenesis by inducing spontaneous DNA damage accumulation in human nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is a major malignant tumor of the head and neck region in southern China. The understanding of its underlying etiology is essential for the development of novel effective therapies. We report for the first time that microRNA-940 (miR-940) significantly suppresses the proliferation of a variety of cancer cell lines, arrests cells cycle, induces caspase-3/7 dependent apoptosis and inhibits the formation of NPC xenograft tumors in mice. We further show that miR-940 directly binds to the 3'-untranslated regions of Nestin mRNA and promotes its degradation. Likewise, depletion of Nestin inhibits tumor cell proliferation, arrest cells at G2/M, induces apoptosis and suppresses xenograft tumor formation in vivo. These functions of miR-940 can be reversed by ectopic expression of Nestin, suggesting that miR-940 regulates cell proliferation and survival through Nestin. Notably, we observed reduced miR-940 and increased Nestin levels in NPC patient samples. Protein microarray revealed that knockdown of Nestin in 5-8F NPC cells alters the phosphorylation of proteins involved in the DNA damage response, suggesting a mechanism for the miR 940/Nestin axis. Consistently, depletion of Nestin induced spontaneous DNA damage accumulation, delayed the DNA damage repair process and increased the sensitivity to irradiation and the chemotherapeutic agent doxorubicin. Collectively, our findings indicate that Nestin, which is downregulated by miR-940, can promote tumorigenesis in NPC cells through involvement in the DNA damage response. The levels of microRNA-940 and Nestin may serve as indicators of cancer status and prognosis. PMID- 25118935 TI - Impaired cell death and mammary gland involution in the absence of Dock1 and Rac1 signaling. AB - Throughout life, the tight equilibrium between cell death and the prompt clearance of dead corpses is required to maintain a proper tissue homeostasis and prevent inflammation. Following lactation, mammary gland involution is triggered and results in the death of excessive epithelial cells that are rapidly cleared by phagocytes to ensure that the gland returns to its prepregnant state. Orthologs of Dock1 (dedicator of cytokinesis 1), Elmo and Rac1 (ras-related C3 botulinum toxin substrate 1) in Caenorhabditis elegans are part of a signaling module in phagocytes that is linking apoptotic cell recognition to cytoskeletal reorganization required for engulfment. In mammals, Elmo1 was shown to interact with the phosphatidylserine receptor Bai1 and relay signals to promote phagocytosis of apoptotic cells. Still, the role of the RacGEF Dock1 in the clearance of dying cells in mammals was never directly addressed. We generated two mouse models with conditional inactivation of Dock1 and Rac1 and revealed that the expression of these genes is not essential in the mammary gland during puberty, pregnancy and lactation. We induced mammary gland involution in these mice to investigate the role of Dock1/Rac1 signaling in the engulfment of cell corpses. Unpredictably, activation of Stat3 (signal transducer and activator of transcription 3), a key regulator of mammary gland involution, was impaired in the absence of Rac1 and Dock1 expression. Likewise, failure to activate properly Stat3 was coinciding with a significant delay in the initiation and progression of mammary gland involution in mutant animals. By using an in vitro phagocytosis assay, we observed that Dock1 and Rac1 are essential to mediate engulfment in epithelial phagocytes. In vivo, cell corpses accumulated at late time points of involution in Dock1 and Rac1 mutant mammary glands. Overall, our study demonstrated an unsuspected role for Dock1/Rac1 signaling in the initiation of mammary gland involution, and also suggested a role for this pathway in the clearance of dead cells by epithelial phagocytes. PMID- 25118938 TI - Detrimental effects of Notch1 signaling activated by cadmium in renal proximal tubular epithelial cells. AB - We examined the roles of Notch1 signaling and its cross-talk with other signaling pathways, including p53 and phosphatidylinositol-3-kinase (PI3K)/Akt, in cadmium induced cellular damage in HK-2 human renal proximal tubular epithelial cells. Following exposure to cadmium chloride (CdCl2), the level of Notch intracellular domain (NICD), the cleaved form of the Notch1 receptor, was increased and accumulated in the nuclear fraction. Knockdown of Notch1 with siRNA or treatment with the gamma-secretase inhibitor, DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl)] S-phenylglycine t-butyl ester), prevented CdCl2-induced morphological change of HK-2 cells and reduction of cell viability. Knockdown of Jagged1 or Jagged2, the ligands of the Notch1 receptor, partially suppressed cadmium cytotoxicity. Inhibition of p53 activity with pifithrin-alpha or inhibition of PI3K with LY294002 suppressed CdCl2-induced cellular damage and elevation of Notch1-NICD. In addition, treatment with the epidermal growth factor receptor (EGFR) inhibitor, AG1478, and the insulin-like growth factor-1 receptor inhibitor, PPP, suppressed both Notch1-NICD accumulation and Akt phosphorylation in HK-2 cells exposed to CdCl2. However, knockdown of Notch1 did not affect CdCl2-induced p53 accumulation and phosphorylation but suppressed phosphorylation of EGFR, Akt, and p70 S6 kinase. Depletion of Notch1 suppressed CdCl2-induced reduction of E cadherin expression and elevation of Snail expression. Furthermore, treatment with SB216763, an inhibitor of glycogen synthase kinase-3, suppressed the potency of LY294002 treatment to reduce Snail expression in HK-2 cells exposed to CdCl2. Knockdown of Snail with siRNA partially prevented HK-2 cells from CdCl2-induced reduction of E-cadherin expression and cellular damage. These results suggest that cadmium exposure induces the activation of Notch1 signaling in renal proximal tubular cells with cooperative activation by the p53 and PI3K/Akt signaling pathways; the resultant expression of Snail, a repressor of E-cadherin expression, might lead to cellular damage by decreasing cell-cell adhesion. PMID- 25118939 TI - FAK competes for Src to promote migration against invasion in melanoma cells. AB - Melanoma is one of the most deadly cancers because of its high propensity to metastasis, a process that requires migration and invasion of tumor cells driven by the regulated formation of adhesives structures like focal adhesions (FAs) and invasive structures like invadopodia. FAK, the major kinase of FAs, has been implicated in many cellular processes, including migration and invasion. In this study, we investigated the role of FAK in the regulation of invasion. We report that suppression of FAK in B16F10 melanoma cells led to increased invadopodia formation and invasion through Matrigel, but impaired migration. These effects are rescued by FAK WT but not by FAK(Y397F) reexpression. Invadopodia formation requires local Src activation downstream of FAK and in a FAK phosphorylation dependant manner. FAK deletion correlates with increased phosphorylation of Tks-5 (tyrosine kinase substrate with five SH3 domain) and reactive oxygen species production. In conclusion, our data show that FAK is able to mediate opposite effects on cell migration and invasion. Accordingly, beneficial effects of FAK inhibition are context dependent and may depend on the cell response to environmental cues and/or on the primary or secondary changes that melanoma experienced through the invasion cycle. PMID- 25118942 TI - Future impacts of nitrogen deposition and climate change scenarios on forest crown defoliation. AB - Defoliation is an indicator for forest health in response to several stressors including air pollutants, and one of the most important parameters monitored in the International Cooperative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests). The study aims to estimate crown defoliation in 2030, under three climate and one nitrogen deposition scenarios, based on evaluation of the most important factors (meteorological, nitrogen deposition and chemical soil parameters) affecting defoliation of twelve European tree species. The combination of favourable climate and nitrogen fertilization in the more adaptive species induces a generalized decrease of defoliation. On the other hand, severe climate change and drought are main causes of increase in defoliation in Quercus ilex and Fagus sylvatica, especially in Mediterranean area. Our results provide information on regional distribution of future defoliation, an important knowledge for identifying policies to counteract negative impacts of climate change and air pollution. PMID- 25118941 TI - Visceral adipose tissue-derived serine protease inhibitor inhibits interleukin 1beta-induced catabolic and inflammatory responses in murine chondrocytes. AB - Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a newly identified member of the adipocytokine family, whose precise role in chondrocyte metabolism remains to be elucidated. The aim of the present study was to investigate the effect of vaspin on chondrocytes. The cell viability and the cytotoxicity of vaspin in chondrocytes were examined. Furthermore, the gene expression of matrix metalloproteinases-2 and -9, a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 and cathepsin D was also examined, as well as the protein production of cyclooxygenase-2, prostaglandin E2 and inducible nitrous oxide synthase following treatment with different concentrations of vaspin in the absence or presence of interleukin-1-beta (IL 1beta). In addition, the protein levels of the inhibitor of nuclear factor-kappaB (IkappaB-alpha) and the phosphorylation of nuclear factor kappa B (NF-kappaB) were investigated. Vaspin was not able to stimulate the proliferation of chondrocytes and demonstrated no significant cytotoxic effect at concentrations of 10-500 ng/ml following coincubation for 24 and 48 h. However, vaspin inhibited IL-1beta-induced production of catabolic factors and inflammatory mediators in chondrocytes, and also suppressed the phosphorylation of NF-kappaB and the degradation of IkappaB-alpha. The data from the present study suggested that vaspin has a protective effect in chondrocyte metabolism and is an important factor in the pathophysiology of osteoarthritis. PMID- 25118943 TI - D'scent of man: a comparative survey of primate chemosignaling in relation to sex. AB - This article is part of a Special Issue (Chemosignals and Reproduction). As highly visual animals, primates, in general, and Old World species (including humans), in particular, are not immediately recognized for reliance in their daily interactions on olfactory communication. Nevertheless, views on primate olfactory acuity and the pervasiveness of their scent signaling are changing, with increased appreciation for the important role of body odors in primate social and sexual behavior. All major taxonomic groups, from lemurs to humans, are endowed with scent-producing organs, and either deposit or exude a wealth of volatile compounds, many of which are known semiochemicals. This review takes a comparative perspective to illustrate the reproductive context of primate signaling, the relevant information content of their signals, the sexually differentiated investigative responses generated, and the behavioral or physiological consequences of message transmission to both signaler and receiver. Throughout, humans are placed alongside their relatives to illustrate the evolutionary continuum in the sexual selection of primate chemosignals. This ever growing body of evidence points to a critical role of scent in guiding the social behavior and reproductive function throughout the primate order. PMID- 25118940 TI - Impulsivity in disorders of food and drug misuse. AB - BACKGROUND: Evidence suggests some overlap between the pathological use of food and drugs, yet how impulsivity compares across these different clinical disorders remains unclear. Substance use disorders are commonly characterized by elevated impulsivity, and impulsivity subtypes may show commonalities and differences in various conditions. We hypothesized that obese subjects with binge-eating disorder (BED) and abstinent alcohol-dependent cohorts would have relatively more impulsive profiles compared to obese subjects without BED. We also predicted decision impulsivity impairment in obesity with and without BED. METHOD: Thirty obese subjects with BED, 30 without BED and 30 abstinent alcohol-dependent subjects and age- and gender-matched controls were tested on delay discounting (preference for a smaller immediate reward over a larger delayed reward), reflection impulsivity (rapid decision making prior to evidence accumulation) and motor response inhibition (action cancellation of a prepotent response). RESULTS: All three groups had greater delay discounting relative to healthy volunteers. Both obese subjects without BED and alcohol-dependent subjects had impaired motor response inhibition. Only obese subjects without BED had impaired integration of available information to optimize outcomes over later trials with a cost condition. CONCLUSIONS: Delay discounting appears to be a common core impairment across disorders of food and drug intake. Unexpectedly, obese subjects without BED showed greater impulsivity than obese subjects with BED. We highlight the dissociability and heterogeneity of impulsivity subtypes and add to the understanding of neurocognitive profiles across disorders involving food and drugs. Our results have therapeutic implications suggesting that disorder specific patterns of impulsivity could be targeted. PMID- 25118944 TI - Successful non-surgical deep uterine transfer of porcine morulae after 24 hour culture in a chemically defined medium. AB - Excellent fertility and prolificacy have been reported after non-surgical deep uterine transfers of fresh in vivo-derived porcine embryos. Unfortunately, when this technology is used with vitrified embryos, the reproductive performance of recipients is low. For this reason and because the embryos must be stored until they are transferred to the recipient farms, we evaluated the potential application of non-surgical deep uterine transfers with in vivo-derived morulae cultured for 24 h in liquid stage. In Experiment 1, two temperatures (25 degrees C and 37 degrees C) and two media (one fully defined and one semi-defined) were assessed. Morulae cultured in culture medium supplemented with bovine serum albumin and fetal calf serum at 38.5 degrees C in 5% CO2 in air were used as controls. Irrespective of medium, the embryo viability after 24 h of culture was negatively affected (P<0.05) at 25 degrees C but not at 37 degrees C compared with the controls. Embryo development was delayed in all experimental groups compared with the control group (P<0.001). Most of the embryos (95.7%) cultured at 37 degrees C achieved the full or expanded blastocyst stage, and unlike the controls, none of them hatched at the end of culture. In Experiment 2, 785 morulae were cultured in the defined medium at 37 degrees C for 24 h, and the resulting blastocysts were transferred to the recipients (n = 24). Uncultured embryos collected at the blastocyst stage (n = 750) were directly transferred to the recipients and used as controls (n = 25). No differences in farrowing rates (91.7% and 92.0%) or litter sizes (9.0 +/- 0.6 and 9.4 +/- 0.8) were observed between the groups. This study demonstrated, for the first time, that high reproductive performance can be achieved after non-surgical deep uterine transfers with short-term cultured morulae in a defined medium, which opens new possibilities for the sanitary, safe national and international trade of porcine embryos and the commercial use of embryo transfer in pigs. PMID- 25118945 TI - Perinatal protein malnutrition affects mitochondrial function in adult and results in a resistance to high fat diet-induced obesity. AB - Epidemiological findings indicate that transient environmental influences during perinatal life, especially nutrition, may have deleterious heritable health effects lasting for the entire life. Indeed, the fetal organism develops specific adaptations that permanently change its physiology/metabolism and that persist even in the absence of the stimulus that initiated them. This process is termed "nutritional programming". We previously demonstrated that mothers fed a Low Protein-Diet (LPD) during gestation and lactation give birth to F1-LPD animals presenting metabolic consequences that are different from those observed when the nutritional stress is applied during gestation only. Compared to control mice, adult F1-LPD animals have a lower body weight and exhibit a higher food intake suggesting that maternal protein under-nutrition during gestation and lactation affects the energy metabolism of F1-LPD offspring. In this study, we investigated the origin of this apparent energy wasting process in F1-LPD and demonstrated that minimal energy expenditure is increased, due to both an increased mitochondrial function in skeletal muscle and an increased mitochondrial density in White Adipose Tissue. Importantly, F1-LPD mice are protected against high-fat diet-induced obesity. Clearly, different paradigms of exposure to malnutrition may be associated with differences in energy expenditure, food intake, weight and different susceptibilities to various symptoms associated with metabolic syndrome. Taken together these results demonstrate that intra-uterine environment is a major contributor to the future of individuals and disturbance at a critical period of development may compromise their health. Consequently, understanding the molecular mechanisms may give access to useful knowledge regarding the onset of metabolic diseases. PMID- 25118950 TI - Near surface magnetic domain observation with ultra-high resolution. AB - Near field magnetic force microscopy (NF-MFM) has been demonstrated to locally observe the magnetic fine structures in nanosized recording bits at an operating distance of 1 nm. The nanoscale magnetic domains, the polarity of surface magnetic charges, as well as the 3D magnetic fields leaking from the bits are investigated via NF-MFM with a soft NiFe tip. A Fourier analysis of the images suggests that the magnetic moment can be determined locally in a volume as small as 5 nanometers. The NF-MFM is crucial to the analysis of surface magnetic features and allows a wide range of future applications, for example, in data storage and biomedicine. PMID- 25118949 TI - Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation. AB - Ionizing radiation can elicit harmful effects on the cardiovascular system at high doses. Endothelial cells are critical targets in radiation-induced cardiovascular damage. Astronauts performing a long-term deep space mission are exposed to consistently higher fluences of ionizing radiation that may accumulate to reach high effective doses. In addition, cosmic radiation contains high linear energy transfer (LET) radiation that is known to produce high values of relative biological effectiveness (RBE). The aim of this study was to broaden the understanding of the molecular response to high LET radiation by investigating the changes in gene expression in endothelial cells. For this purpose, a human endothelial cell line (EA.hy926) was irradiated with accelerated nickel ions (Ni) (LET, 183 keV/um) at doses of 0.5, 2 and 5 Gy. DNA damage was measured 2 and 24 h following irradiation by gamma-H2AX foci detection by fluorescence microscopy and gene expression changes were measured by microarrays at 8 and 24 h following irradiation. We found that exposure to accelerated nickel particles induced a persistent DNA damage response up to 24 h after treatment. This was accompanied by a downregulation in the expression of a multitude of genes involved in the regulation of the cell cycle and an upregulation in the expression of genes involved in cell cycle checkpoints. In addition, genes involved in DNA damage response, oxidative stress, apoptosis and cell-cell signaling (cytokines) were found to be upregulated. An in silico analysis of the involved genes suggested that the transcription factors, E2F and nuclear factor (NF)-kappaB, may be involved in these cellular responses. PMID- 25118947 TI - Transcriptome analysis of red swamp crawfish Procambarus clarkii reveals genes involved in gonadal development. AB - BACKGROUND: The red swamp crawfish, Procambarus clarkii, has become one of the most economically important cultured species in China. Currently, little is known about the gonadal development of this species. Isolation and characterization of genes are an initial step towards understanding gonadal development of P. clarkii. RESULTS: Using the 454 pyrosequencing technology, we obtained a total of 1,134,993 high quality sequence reads from the crawfish testis and ovary libraries. We aimed to identify different genes with a potential role in gonad development. The assembly formed into 22,652 isotigs, distributed by GO analysis across 55 categories in the three ontologies, 'molecular function', 'cellular component', and 'biological processes'. Comparative transcript analysis showed that 1,720 isotigs in the ovary were up-regulated and 2138 isotigs were down regulated. Several gonad development related genes, such as vitellogenin, cyclin B, cyclin-dependent kinases 2, Dmc1 and ubiquitin were identified. Quantitative real-time PCR verified the expression profiles of 14 differentially expressed genes, and confirmed the reliability of the 454 pyrosequencing. CONCLUSIONS: Our findings provide an archive for future research on gonadal development at a molecular level in P. clarkii and other crustacean. This data will be helpful to develop new ideas for artificial regulation of the reproductive process in crawfish aquaculture. PMID- 25118952 TI - A tailor-made nucleoside-based colourimetric probe of formic acid. AB - A ratiometric, specific probe of formic acid has been developed. It is based on intermolecular nucleobase-pairing of inosine-capped plasmonic nanoparticles to form nucleoside channels, which are destabilised by the analyte. PMID- 25118951 TI - A population-based study of corneal arcus and its risk factors in Iran. AB - PURPOSE: To determine the prevalence of corneal arcus, its risk factors, and its relationship to ocular and visual indices. METHODS: In this cross-sectional study, 300 clusters were randomly selected from Shahroud in the north of Iran, using multistage sampling. A total of 20 people were invited to participate from each cluster. After enrollment, all optometric, biometric and ophthalmic exams were conducted on site. RESULTS: Of 6311 people invited, 5190 (82.2%) participated in the study. The prevalence of corneal arcus was 23.3% (95% confidence interval, CI, 22.1-24.6), and 98.4% were bilateral cases. The prevalence of corneal arcus was higher in men (odds ratio, OR, 2.02, 95% CI 1.8 2.3, p < 0.001) and increased with age (OR 1.1/year, p < 0.001). In a multivariable-adjusted regression model, age (OR 1.1/year, p = 0.006), male sex (OR 1.30, p = 0.001), diabetes (OR 0.7, p < 0.001), smoking (OR 1.5, p = 0.003), outdoor activity (OR 1.4, p = 0.006), systolic blood pressure (OR 1.01, p = 0.012), and diastolic blood pressure (OR 0.99, p = 0.016) were significantly correlated with corneal arcus. Including biometric components in another model, corneal thickness (OR 0.99, p < 0.001), anterior chamber depth (OR 0.68, p < 0.001) and corneal radius of curvature (OR 1.59, p < 0.001) were significantly correlated with corneal arcus. CONCLUSION: This study adds valuable information to the epidemiology of corneal arcus in Iran and the Middle East. In people aged over 60 years, nearly 50% of the study population had corneal arcus. Older age, male sex, smoking, and systolic hypertension were risk factors for corneal arcus. Corneal arcus was also associated with thin and flat corneas and shallow anterior chamber depth. PMID- 25118953 TI - Functional analyses on antioxidant, anti-inflammatory, and antiproliferative effects of extracts and compounds from Ilex latifolia Thunb., a Chinese bitter tea. AB - Ilex latifolia Thunb., widely distributed in China, has been used as a functional food and drunk for a long time. This study was aimed to identify the bioactive constituents with antioxidant, antitumor, and anti-inflammatory properties. I. latifolia was extracted with 95% ethanol and then partitioned into four fractions: petroleum ether fraction, ethyl acetate fraction, n-butanol fraction, and water fraction. Results showed that the ethyl acetate fraction was found to have significant ferric reducing antioxidant power activity, DPPH radical scavenging activity, and oxygen radical absorbance capacity, cytotoxicity against human cervix carcinoma HeLa cells, and inhibitory effect on NO production in macrophage RAW 264.7 cells. Five compounds were isolated from the ethyl acetate fraction, and they were identified as ethyl caffeate (1), ursolic acid (2), chlorogenic acid (3), 3,4-di-O-caffeoylquinic acid methyl ester (4), and 3,5-di-O caffeoylquinic acid methyl ester (5), the last two of which were isolated for the first time from I. latifolia. Compounds 4 and 5 exhibited cytotoxicity actions against tumor cell line. Compound 3 showed the strongest anti-inflammatory activity of all the compounds. The results obtained in this work might contribute to the understanding of biological activities of I. latifolia and further investigation on its potential application values for food and drug. PMID- 25118955 TI - Images in Anesthesiology: Coexisting Aortic Stenosis and Left Ventricular Outflow Tract Obstruction. PMID- 25118954 TI - Spontaneous intracranial hypotension: presentation, diagnosis, and treatment. PMID- 25118957 TI - Controlling the minimal self assembly of "complex" polyoxometalate clusters. AB - Despite the vast number of polyoxometalate clusters now known, an ongoing and important challenge is to understand causality in the assembly of "complex" clusters at a mechanistic level, since this is the only way the rational, targeted synthesis of new compounds will ever be achieved. Often, the complexity of the reactions themselves makes such investigations near impossible, as very small changes can often make dramatic differences. Herein, we explore a very simple [A + B] binary synthetic system that gives rise to the facile assembly of two isomeric anions, [Fe(III)(H2O)2{gamma-Fe(III)SiW9O34(H2O)}2](11-) (1) and [Fe(III)(H2O)2{gamma-Fe(III)2SiW8O33(H2O)2}{gamma-SiW10O35}](11-) (2), which can be formed as individual and dimeric species (3) and (4). Furthermore, the simple binary nature of this synthetic system allowed its investigation by a comprehensive time-resolved ESI-MS analysis, yielding unprecedented mechanistic information regarding the initial interactions and reorganizations of the {gamma SiW10} precursor in the presence of Fe(2+). PMID- 25118956 TI - Synergetic effect of Zn substitution on the electron and phonon transport in Mg2Si0.5Sn0.5-based thermoelectric materials. AB - Mg2Si1-xSnx alloys are a prospective material for thermoelectric generators at moderate temperatures. The thermoelectric properties of Mg2Si0.5Sn0.5-based thermoelectric materials with only Zn substitution or Zn/Sb co-doping were investigated. Isoelectronic Zn substitution did not affect the carrier concentration, but improved the carrier mobility. Zn atoms incorporated into a Sb doped Mg2Si0.5Sn0.5 matrix simultaneously boosted the power factor and suppressed the lattice thermal conductivity, leading to an enhancement of the thermoelectric figure of merit ZT of the resulting bulk materials. The interplay between the electron and phonon transport of Mg2Si0.5Sn0.49Sb0.01 substituted with Zn at Mg sites results in an enhancement of the ZT by 25% at ~730 K, from ZT~ 0.8 in Mg2Si0.5Sn0.49Sb0.01 to ZT~ 1.0 in Mg1.98Zn0.02Si0.5Sn0.49Sb0.01. Solid solutions in the Mg2Si-Mg2Sn system appear to be more promising for thermoelectric applications. PMID- 25118958 TI - Label-free single cell kinetics of the invasion of spheroidal colon cancer cells through 3D Matrigel. AB - This article reports label-free, real-time, and single-cell quantification of the invasion of spheroidal colon cancer cells through three-dimensional (3D) Matrigel using a resonant waveguide grating (RWG) imager. This imager employs a time resolved swept wavelength interrogation scheme to monitor cell invasion and adhesion with a temporal resolution up to 3 s and a spatial resolution of 12 MUm. As the model system, spheroids of human colorectal adenocarcinoma HT-29 cells are generated by culturing the cells in 96-well round-bottom ultralow attachment plates. 3D Matrigel is formed by its gelation in 384-well RWG biosensor microplates. The invasion and adhesion of spheroidal HT29 cells is initiated by placing individual spheroids onto the Matrigel-coated biosensors. The time series RWG images are obtained and used to extract the optical signatures arising from the adhesion after the cells are dissociated from the spheroids and invade through the 3D Matrigel. Compound profiling shows that epidermal growth factor accelerates cancer cell invasion, while vandetanib, a multitarget kinase inhibitor, dose-dependently inhibits invasion. This study demonstrates that the label-free imager can monitor in real-time the invasion of spheroidal cancer cells through 3D matrices. PMID- 25118959 TI - Zn(II)-benzotriazolate clusters based amide functionalized porous coordination polymers with high CO2 adsorption selectivity. AB - Two new porous coordination polymers (PCPs) based on different nanosized C3 symmetry ligands and Zn(II)-benzotriazolate clusters have been synthesized solvothermally. Both of the desolvated complexes show selective uptake of CO2 over CH4 and N2 at ambient temperature. PMID- 25118960 TI - Facile formation of ordered vertical arrays by droplet evaporation of Au nanorod organic solutions. AB - Droplet evaporation is a simple method to induce organization of Au nanorods into ordered superstructures. In general, the self-assembly process occurs by evaporation of aqueous suspensions under strictly controlled experimental conditions. Here we present formation of large area ordered vertical arrays by droplet evaporation of Au nanorod organic suspensions. The uncontrolled (free air) evaporation of such suspensions yielded to formation of ordered nanorod domains covering the entire area of a 5 mm diameter droplet. Detailed investigation of the process revealed that nanorods organized into highly ordered vertical domains at the interface between solvent and air on a fast time scale (minutes). The self-assembly process mainly depended on the initial concentration of nanorod solution and required minimal control of other experimental parameters. Nanorod arrays displayed distinct optical properties which were analyzed by optical imaging and spectroscopy and compared to results obtained from theoretical calculations. The potential use of synthesized arrays as surface enhanced Raman scattering probes was demonstrated with the model molecule 4 aminobenzenthiol. PMID- 25118961 TI - Selective peptide modifications via ruthenium-catalyzed allylic alkylations. AB - Ruthenium-catalyzed allylic alkylations are an interesting alternative to palladium-catalyzed processes, since they can provide products which are not accessible under Pd-catalysis. Chiral terminal allylic substrates can be reacted with perfect stereo- and regioretention, and also (Z)-configured allylic substrates can be converted isomerization-free. This allows highly stereoselective modifications of peptides at glycine subunits. The configuration at the alpha-position of the new generated alpha-amino acid can be controlled by the chiral peptide chain, and at the beta-position by using chiral allylic substrates. PMID- 25118963 TI - Management of sexually transmitted infections in New York State health care organizations: who is thinking about the quality of STI care? AB - BACKGROUND: Rising rates of sexually transmitted infections (STIs) warrant a renewed focus on the management of STIs in health care organizations. The extent to which hospitals and community health centers (CHCs) have established processes and allocated staff for the management of STIs within their organizations remains poorly understood. METHODS: A New York State Department of Health survey was distributed electronically through a closed state communication network to targeted administrators at New York State hospitals and CHCs. The survey asked if STI management in their facilities included the following: the ability to measure and report rates of STIs, a process to assess the quality of STI care and treatment outcomes, and a centralized person/unit to coordinate its work throughout the facility. Multivariate analysis was performed to identify whether organizational characteristics were associated with survey findings. RESULTS: Ninety-five percent (243/256) of hospitals and CHCs responded to the survey. Fifty percent of respondents had a person or unit to report rates of STIs; 30% reported an organization-wide process for monitoring the quality of STI care, which, according to the multivariate analysis, was associated with CHCs; only 23% reported having a centralized person or unit for coordinating STI management. CONCLUSIONS: Most facilities report STI cases to comply with public health surveillance requirements but do not measure infection rates, assess the quality of STI care, or coordinate its work throughout the facility. The development of this organizational capacity would likely decrease STI rates, improve treatment outcomes, and address local public health goals. PMID- 25118964 TI - A self-assessed questionnaire can help in the diagnosis of pelvic inflammatory disease. AB - BACKGROUND: Pelvic inflammatory disease (PID) is often responsible for acute pelvic pain, yet its clinical diagnosis is difficult. The aim of this study was to develop and validate prediction rules for the diagnosis of PID in patients seen for acute pelvic pain, based solely on a self-assessed questionnaire. METHODS: From September 2006 to April 2008, 499 consecutive patients presenting at the gynecology emergency departments of 5 hospitals for acute pelvic pain completed a Self-Assessment Questionnaire for Gynecological Emergencies. Seventy three were identified as having a PID. Two-thirds of the database was randomly selected for the derivation of the prediction rules, and the other third was used for internal validation. We developed 2 scores, one that rules out a diagnosis of PID and one that predicts PID, based on multiple logistic regression with jackknife estimates. These scores were then validated with the validation data set. RESULTS: Four variables were independently associated with PID: scattered pain radiation and/or diffuse pain, insidious pain, peritoneal irritation, and abnormal vaginal discharge. They were used to create a sensitive prediction model that rules out PID. Four other variables were used to build another model that predicted PID with high specificity: abnormal vaginal discharge, bilateral pelvic pain, constipation, and presence of an intrauterine device. The probability of PID for the patients in the low-risk group was 1.1% (95% confidence interval, 0.03-5.8), and the probability of PID in the high-risk group was 55% (95% confidence interval, 31.5-76.9). CONCLUSION: These 2 prediction rules that classify patients in low risk or high risk of PID, based on simple items collected by a self-assessed questionnaire that are composed only of case history and autodescription of the pain, may prove useful for diagnosing or ruling out PID in patients with acute pelvic pain. PMID- 25118962 TI - Effects of two Chinese herbal formulae for the treatment of moderate to severe stable chronic obstructive pulmonary disease: a multicenter, double-blind, randomized controlled trial. AB - OBJECTIVE: The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD. METHODS: A multicenter, double blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol. RESULTS: A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL 17(P<0.05), IL-1beta (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-alpha. Both treatments slightly descended TGF-beta1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups. CONCLUSIONS: BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general. TRIAL REGISTRATION: Chinese Clinical Trial Register center ChiCTR-TRC-09000530. PMID- 25118965 TI - Bone involvement in secondary syphilis: a case report and systematic review of the literature. AB - Bone involvement is an unusual manifestation of secondary syphilis, but little information is available in the English-language literature. We carried out a systematic review of the English-language literature from 1964 to 2013, describing cases of secondary syphilis with bone involvement. We also describe a case of secondary syphilis with multiple osteolytic lesions, mimicking metastatic cancer or myeloma, which was included in an analysis of 37 eligible cases of secondary syphilis with bone involvement. Of these 37 patients, 28 (76%) patients were male, and the median age was 32 years (range, 12-64 years). Eleven (30%) patients had human immunodeficiency virus (HIV) infection with a median CD4 lymphocyte count of 343 cells/mm (range, 130-689 cells/mm). The diagnosis of early syphilis was suspected based on mucocutaneous findings in 28 (76%) cases. In the remaining 9 (24%) cases, high titers of nontreponemal serologic tests were the only evidence of early syphilis. The median venereal disease research laboratory (VDRL) titer was 1:64 (range, 1:8-1:320), and median rapid plasma reagin (RPR) titer was 1:64 (range, 1:16-1:512). The bones most often affected were long bones of the limbs (n = 22) and skull (n = 21). The bone lesions were multifocal in 27 (73%) cases and osteolytic in 19 (51%) cases. The treatment of syphilitic bone lesions was medical only in most patients, and prognosis was favorable with high-dose penicillin therapy. Clinical features and outcome between HIV-uninfected and HIV-infected patients were not different. Knowledge of this rare entity may lead to early diagnosis and appropriate management. PMID- 25118966 TI - Chlamydia screening for sexually active young women under the Affordable Care Act: new opportunities and lingering barriers. AB - The Affordable Care Act of 2010 (ACA) contains a provision requiring private insurers issuing or renewing plans on or after September 23, 2010, to provide, without cost sharing, preventive services recommended by US Preventive Services Task Force (grades A and B), among other recommending bodies. As a grade A recommendation, chlamydia screening for sexually active young women 24 years and younger and older women at risk for chlamydia falls under this requirement. This article examines the potential effect on chlamydia screening among this population across private and public health plans and identifies lingering barriers not addressed by this legislation. Examination of the impact on women with private insurance touches upon the distinction between coverage under grandfathered plans, where the requirement does not apply, and nongrandfathered plans, where the requirement does apply. Acquisition of private health insurance through health insurance Marketplaces is also discussed. For public health plans, coverage of preventive services without cost sharing differs for individuals enrolled in standard Medicaid, covered under the Medicaid expansion included in the ACA, or those enrolled under the Children's Health Insurance Program or who fall under Early, Periodic, Screening, Diagnosis and Treatment criteria. The discussion of lingering barriers not addressed by the ACA includes the uninsured, physician reimbursement, cost sharing, confidentiality, low rates of appropriate sexual history taking by providers, and disclosures of sensitive information. In addition, the role of safety net programs that provide health care to individuals regardless of ability to pay is examined in light of the expectation that they also remain a payer of last resort. PMID- 25118968 TI - Molecular typing of Treponema pallidum: identification of a new sequence of tp0548 gene in Shandong, China. PMID- 25118967 TI - The cost of implementing rapid HIV testing in sexually transmitted disease clinics in the United States. AB - INTRODUCTION: Rapid HIV testing in high-risk populations can increase the number of persons who learn their HIV status and avoid spending clinic resources to locate persons identified as HIV infected. METHODS: We determined the cost to sexually transmitted disease (STD) clinics of point-of-care rapid HIV testing using data from 7 public clinics that participated in a randomized trial of rapid testing with and without brief patient-centered risk reduction counseling in 2010. Costs included counselor and trainer time, supplies, and clinic overhead. We applied national labor rates and test costs. We calculated median clinic start up costs and mean cost per patient tested, and projected incremental annual costs of implementing universal rapid HIV testing compared with current testing practices. RESULTS: Criteria for offering rapid HIV testing and methods for delivering nonrapid test results varied among clinics before the trial. Rapid HIV testing cost an average of US $22/patient without brief risk reduction counseling and US $46/patient with counseling in these 7 clinics. Median start-up costs per clinic were US $1100 and US $16,100 without and with counseling, respectively. Estimated incremental annual costs per clinic of implementing universal rapid HIV testing varied by whether or not brief counseling is conducted and by current clinic testing practices, ranging from a savings of US $19,500 to a cost of US $40,700 without counseling and a cost of US $98,000 to US $153,900 with counseling. CONCLUSIONS: Universal rapid HIV testing in STD clinics with same-day results can be implemented at relatively low cost to STD clinics, if brief risk reduction counseling is not offered. PMID- 25118969 TI - The molecular typing data of recently identified subtype 11q/j of Treponema pallidum subsp. pallidum suggest imported case of yaws. PMID- 25118970 TI - When is syphilis not syphilis? Or is it? PMID- 25118971 TI - Age-specific chlamydial infection among pregnant women in the United States: evidence for updated recommendations. AB - BACKGROUND: In the United States, chlamydia screening has been recommended for all pregnant women by the Centers for Disease Control and Prevention (CDC) but only for pregnant women who are at increased risk by the US Preventive Services Task Force (USPSTF). Very limited evidence, such as age-specific chlamydia positivity in pregnant women, has been used to develop these recommendations. METHODS: We analyzed data from a large commercial laboratory corporation in the United States in 2013. At the first prenatal visit made by women aged 15 to 44 years for whom a chlamydia test was performed between June 2008 and July 2010, we estimated positivity of chlamydia by age, insurance coverage, geographic region, and test type. RESULTS: Of 601,001 pregnant women aged 15 to 44 years who had routine prenatal care, 62.9% had private insurance and 32.9% had Medicaid coverage, 60.3% resided in the South region, and 43.2% were aged 15 to 24 years, 26.8% were aged 25 to 29 years, and 19.1% were aged 30 to 34 years. Chlamydia positivity was 3.6% overall, and significantly decreased as age increased (15-19 years: 9.6 %; 20-24 years: 5.2%; 25-29 years: 1.8%; 30-34 years: 0.9%; and 35-44 years: 0.6%; P < 0.05). CONCLUSIONS: Our findings of higher positivity among younger pregnant women suggest that the yield is likely to be greater from screening younger pregnant women than from screening older pregnant women to identify chlamydia infection. The benefits of harmonizing CDC and USPSTF recommendations for pregnant women could be explored by reviewing age-specific positivity data and estimating the frequency of prenatal adverse health outcomes caused by chlamydia to develop consensus regarding the age limit for pregnant women who should be screened. PMID- 25118972 TI - Congenital syphilis investigation processes and timing in Louisiana. AB - BACKGROUND: Congenital syphilis (CS) is a potentially life-threatening yet preventable infection. State and local public health jurisdictions conduct investigations of possible CS cases to determine case status and to inform public health prevention efforts. These investigations occur when jurisdictions receive positive syphilis test results from pregnant women or from infants. METHODS: We extracted data from Louisiana's electronic case management system for 328 infants investigated as possible CS cases in 2010 to 2011. Using date stamps from the case management system, we described CS investigations in terms of processes and timing. RESULTS: Eighty-seven investigations were prompted by positive test results from women who were known to be pregnant by the health jurisdiction, and 241 investigations were prompted by positive syphilis test results from infants. Overall, investigations required a median of 101 days to complete, although 25% were complete within 36 days. Investigations prompted by positive test results from infants required a median of 135 days to complete, and those prompted by positive test results from pregnant women required a median of 41 days. CONCLUSIONS: Three times as many CS investigations began with reported positive syphilis test results from infants as from pregnant women, and these investigations required more time to complete. When CS investigations begin after an infant's birth, the opportunity to ensure that women are treated during pregnancy is missed, and surveillance data cannot inform prevention efforts on a timely basis. Consistently ascertaining pregnancy status among women whose positive syphilis test results are reported to public health jurisdictions could help to assure timely CS prevention efforts. PMID- 25118973 TI - Cross-sectional study of genital, rectal, and pharyngeal Chlamydia and gonorrhea in women in rural South Africa. AB - BACKGROUND: Epidemiological data of genital chlamydia and gonorrhea, required to inform design and implementation of control programs, are limited for rural Africa. There are no data on the prevalence of rectal or pharyngeal infections among African women. METHODS: A cross-sectional study of 604 adult women visiting 25 primary health care facilities in rural South Africa was conducted. Vaginal, anorectal, and oropharyngeal swabs were tested for Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: Prevalence of genital chlamydia was 16% and that of gonorrhea was 10%; rectal chlamydial infection was diagnosed in 7.1% and gonococcal in 2.5% of women. One woman had pharyngeal chlamydia. Most women with genital chlamydia (61%) and gonorrhea (57%) were asymptomatic. Independent risk factors for genital chlamydia were younger age (adjusted odds ratio [aOR], 0.96 per year; 95% confidence interval [CI], 0.93-0.98), hormonal contraceptive use (aOR, 2.2; 95% CI, 1.3-3.7), pregnancy (aOR, 2.4; 95% CI, 1.3-4.4), and intravaginal cleansing (aOR, 1.7; 95% CI, 1.04-2.8). Intravaginal cleansing was associated with genital gonorrhea (aOR, 1.9; 95% CI, 1.1-3.3). CONCLUSIONS: Genital and rectal, but not pharyngeal, chlamydia and gonorrhea are highly prevalent and frequently asymptomatic in women in rural South Africa. Young women attending health care facilities for antenatal care or family planning should be prioritized in control efforts. PMID- 25118974 TI - Flexible graphene-graphene composites of superior thermal and electrical transport properties. AB - Graphene is known for high thermal and electrical conductivities. In the preparation of neat carbon materials based on graphene, a common approach has been the use of well-exfoliated graphene oxides (GOs) as the precursor, followed by conversion to reduced GOs (rGOs). However, rGOs are more suitable for the targeted high electrical conductivity achievable through percolation but considerably less effective in terms of efficient thermal transport dictated by phonon progression. In this work, neat carbon films were fabricated directly from few-layer graphene sheets, avoiding rGOs completely. These essentially graphene graphene composites were of a metal-like appearance and mechanically flexible, exhibiting superior thermal and electrical transport properties. The observed thermal and electrical conductivities are higher than 220 W/m . K and 85000 S/m, respectively. Some issues in the further development of these mechanically flexible graphene-graphene nanocomposite materials are discussed and so are the associated opportunities. PMID- 25118975 TI - Enhancing Patient Flexibility of Subcutaneous Immunoglobulin G Dosing: Pharmacokinetic Outcomes of Various Maintenance and Loading Regimens in the Treatment of Primary Immunodeficiency. AB - INTRODUCTION: Standard treatment for patients with primary immunodeficiency (PID) is monthly intravenous immunoglobulin (IVIG), or weekly/biweekly subcutaneous immunoglobulin (SCIG) infusion. We used population pharmacokinetic modeling to predict immunoglobulin G (IgG) exposure following a broad range of SCIG dosing regimens for initiation and maintenance therapy in patients with PID. METHODS: Simulations of SCIG dosing were performed to predict IgG concentration-time profiles and exposure metrics [steady-state area under the IgG concentration-time curve (AUC), IgG peak concentration (C max), and IgG trough concentration (C min) ratios] for various infusion regimens. RESULTS: The equivalent of a weekly SCIG maintenance dose administered one, two, three, five, or seven times per week, or biweekly produced overlapping steady-state concentration-time profiles and similar AUC, C max, and C min values [95% confidence interval (CI) for ratios was 0.98-1.03, 0.95-1.09, and 0.92-1.08, respectively]. Administration every 3 or 4 weeks resulted in higher peaks and lower troughs; the 95% CI of the AUC, C max, and C min ratios was 0.97-1.04, 1.07-1.26, and 0.86-0.95, respectively. IgG levels >7 g/L were reached within 1 week using a loading dose regimen in which the weekly maintenance dose was administered five times in the first week of treatment. In patients with very low endogenous IgG levels, administering 1.5 times the weekly maintenance dose five times in the first week of treatment resulted in a similar response. CONCLUSIONS: The same total weekly SCIG dose can be administered at different intervals, from daily to biweekly, with minimal impact on serum IgG levels. Several SCIG loading regimens rapidly achieve adequate serum IgG levels in treatment-naive patients. PMID- 25118977 TI - Composition-dependent interfacial abruptness in Au-catalyzed Si(1-x)Ge(x)/Si/Si(1 x)Ge(x) nanowire heterostructures. AB - As MOSFETs are scaled down, power dissipation remains the most challenging bottleneck for nanoelectronic devices. To circumvent this challenge, alternative devices such as tunnel field effect transistors are potential candidates, where the carriers are injected by a much less energetically costly quantum band to band tunneling mechanism. In this context, axial nanowire heterointerfaces with well-controlled interfacial abruptness offer an ideal structure. We demonstrate here the effect of tuning the Ge concentration in a Si1-xGex part of the nanowire on the Si/Si1-xGex and Si1-xGex/Si interfacial abruptness in axial Si-Si1-xGex nanowire heterostructures grown by the Au-catalyzed vapor-liquid-solid method. The two heterointerfaces are always asymmetric irrespective of the Ge concentration or nanowire diameter. For a fixed diameter, the value of interface abruptness decreases with increasing the Ge content for the Si/Si1-xGex interface but shows no strong Ge dependence at the Si1-xGex/Si interface where it features a linear correlation with the nanowire diameter. To rationalize these findings, a kinetic model for the layer-by-layer growth of nanowire heterostructures from a ternary Au-Ge-Si alloy is established that predicts a discrepancy in Ge concentration in the layer and the catalyst droplet. The Ge concentration in each layer is predicted to be dependent on the composition of the preceding layer. The most abrupt heterointerface (~5 nm) is achieved by growing Si1-xGex with x = 0.85 on Si in a 25 nm diameter nanowire. PMID- 25118976 TI - Medically complex pregnancies and early breastfeeding behaviors: a retrospective analysis. AB - BACKGROUND: Breastfeeding is beneficial for women and infants, and medical contraindications are rare. Prenatal and labor-related complications may hinder breastfeeding, but supportive hospital practices may encourage women who intend to breastfeed. We measured the relationship between having a complex pregnancy (entering pregnancy with hypertension, diabetes, or obesity) and early infant feeding, accounting for breastfeeding intentions and supportive hospital practices. METHODS: We performed a retrospective analysis of data from a nationally-representative survey of women who gave birth in 2011-2012 in a US hospital (N = 2400). We used logistic regression to examine the relationship between pregnancy complexity and breastfeeding. Self-reported prepregnancy diabetes or hypertension, gestational diabetes, or obesity indicated a complex pregnancy. The outcome was feeding status 1 week postpartum; any breastfeeding was evaluated among women intending to breastfeed (N = 1990), and exclusive breastfeeding among women who intended to exclusively breastfeed (N = 1418). We also tested whether breastfeeding intentions or supportive hospital practices mediated the relationship between pregnancy complexity and infant feeding status. RESULTS: More than 33% of women had a complex pregnancy; these women had 30% lower odds of intending to breastfeed (AOR = 0.71; 95% CI, 0.52-0.98). Rates of intention to exclusively breastfeed were similar for women with and without complex pregnancies. Women who intended to breastfeed had similar rates of any breastfeeding 1 week postpartum regardless of pregnancy complexity, but complexity was associated with >30% lower odds of exclusive breastfeeding 1 week among women who intended to exclusively breastfeed (AOR = 0.68; 95% CI, 0.47 0.98). Supportive hospital practices were strongly associated with higher odds of any or exclusive breastfeeding 1 week postpartum (AOR = 4.03; 95% CI, 1.81-8.94; and AOR = 2.68; 95% CI, 1.70-4.23, respectively). CONCLUSIONS: Improving clinical and hospital support for women with complex pregnancies may increase breastfeeding rates and the benefits of breastfeeding for women and infants. PMID- 25118979 TI - Normal controlled attenuation parameter values: a prospective study of healthy subjects undergoing health checkups and liver donors in Korea. AB - BACKGROUND/AIMS: The controlled attenuation parameter (CAP) is a noninvasive method of assessing hepatic steatosis. We defined the normal range of CAP values in healthy subjects and evaluated the associated factors. METHODS: CAP values were measured in a cohort of healthy subjects who were screened as living liver transplantation donors and those who underwent health checkups. Subjects with current or a history of chronic liver disease, abnormalities on liver-related laboratory tests, or fatty liver on ultrasonography or biopsy were excluded. RESULTS: The mean age of the 264 recruited subjects (131 males and 133 females; 76 potential liver donors and 188 subjects who had undergone health checkups) was 49.2 years. The mean CAP value was 224.8 +/- 38.7 dB/m (range 100.0-308.0 dB/m), and the range of normal CAP values (5th-95th percentiles) was 156.0-287.8 dB/m. The mean CAP value was significantly higher in the health checkup than in the potential liver donor group (227.5 +/- 42.0 vs. 218.2 +/- 28.3 dB/m, P = 0.040). CAP values did not differ significantly according to gender or age in either group (all P > 0.05). In a multivariate linear regression analysis, body mass index (beta = 0.271, P = 0.024) and triglyceride levels (beta = 0.348, P = 0.008) were found to be independently associated with CAP values. CONCLUSION: We determined the normal range of CAP values and found that body mass index and triglyceride levels were associated with the CAP values of healthy subjects. PMID- 25118981 TI - Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes. AB - Reperfusion-induced ventricular fibrillation (VF) severely threatens the lives of post-myocardial infarction patients. Carbon monoxide (CO)--produced by haem oxygenase in cardiomyocytes--has been reported to prevent VF through an unknown mechanism of action. Here, we report that CO prolongs action potential duration (APD) by inhibiting a subset of inward-rectifying potassium (Kir) channels. We show that CO blocks Kir2.2 and Kir2.3 but not Kir2.1 channels in both cardiomyocytes and HEK-293 cells transfected with Kir. CO directly inhibits Kir2.3 by interfering with its interaction with the second messenger phosphatidylinositol (4,5)-bisphosphate (PIP2). As the inhibition of Kir2.2 and Kir2.3 by CO prolongs APD in myocytes, cardiac Kir2.2 and Kir2.3 are promising targets for the prevention of reperfusion-induced VF. PMID- 25118980 TI - The importance of intraoperative selenium blood levels on organ dysfunction in patients undergoing off-pump cardiac surgery: a randomised controlled trial. AB - INTRODUCTION: Cardiac surgery is accompanied by an increase of oxidative stress, a significantly reduced antioxidant (AOX) capacity, postoperative inflammation, all of which may promote the development of organ dysfunction and an increase in mortality. Selenium is an essential co-factor of various antioxidant enzymes. We hypothesized a less pronounced decrease of circulating selenium levels in patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less intraoperative oxidative stress. METHODS: In this prospective randomised, interventional trial, 40 patients scheduled for elective coronary artery bypass grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if both techniques were feasible for the single patient. Clinical data, myocardial damage assessed by myocard specific creatine kinase isoenzyme (CK-MB), circulating whole blood levels of selenium, oxidative stress assessed by asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by glutathionperoxidase (GPx) levels and perioperative inflammation represented by interleukin-6 (IL-6) levels were measured at predefined perioperative time points. RESULTS: At end of surgery, both groups showed a comparable decrease of circulating selenium concentrations. Likewise, levels of oxidative stress and IL 6 were comparable in both groups. Selenium levels correlated with antioxidant capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to myocardial damage (CK-MB: r = -0.571, p<0.001). Low postoperative selenium levels had a high predictive value for the occurrence of any postoperative complication. CONCLUSIONS: OPCAB surgery is not associated with less oxidative stress and a better preservation of the circulating selenium pool than on-pump surgery. Low postoperative selenium levels are predictive for the development of complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT01409057. PMID- 25118982 TI - Thermal effects of cold light sources used in otologic surgery. AB - The objective of this study was to investigate the thermal effects of cold light sources and endoscopes on the inner ear. 25 male guinea pigs were assigned equally to five groups (1: Halogen-1 min, 2: Halogen-5 min, 3: Xenon-1 min, 4: Xenon-5 min, 5: Controls). After both bullae of the guinea pigs were opened, light sources and endoscopes were positioned in the middle ears of the first four groups for specific time periods. DPOAE and ABR tests were conducted on all animals at the beginning of the study, at the end of surgery, and 2 h after surgery. The temperatures of cold light sources were measured by a thermocouple thermometer, and the surface temperatures of the endoscopes were measured by an infrared thermometer. DPOAE and ABR measurements performed right after and 2 h after surgery in group 1, 2, 3, and 5 did not reveal any significant difference. In group 4, DPOAE values were significantly lower and ABR threshold values were significantly higher than those in the other groups, right after and 2 h after surgery. Thermocouple thermometer readings showed that, after the first minute, the Xenon light source generated significantly more temperature rise than the Halogen light source. The surface temperatures of all endoscopes returned to normal approximately 1 min after light sources were turned off. Our study demonstrated that when an endoscope using a Xenon light source was applied to the middle ear for a specific time periods, inner ear functions deteriorated, as reflected by audiologic tests. PMID- 25118983 TI - ABCB1 C3435T polymorphism and the risk of ischemic heart disease: a meta analysis. AB - ATP binding cassette transporter 1 (ABCB1) plays a critical role in the development and progression of cardiovascular disease. Emerging evidence suggests that common functional polymorphisms in the ABCB1 gene might have an impact on an individual's susceptibility to ischemic heart disease, but individually published results are inconclusive. The MEDLINE (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945 2013), and the Chinese Biomedical Database (CBM; 1982-2013) were searched without language restrictions. Meta-analysis was performed with the use of the STATA statistical software. Odds ratios (OR) with their 95% confidence intervals (95% CIs) were calculated. Seven case-control studies with a total of 2310 myocardial infarction (MI) patients and 10,506 acute coronary syndrome (ACS) patients met the inclusion criteria. Our meta-analysis results indicated that ABCB1 C3435T polymorphism may be associated with an increased risk of MI and ACS, especially among Asian populations (T allele vs. C allele: OR=1.40, 95% CI=1.31-1.49, ph=0.058). Meta-regression analyses showed that clinical subtype and ethnicity may be the main sources of heterogeneity (T allele vs. C allele: OR=1.16, 95% CI=0.97-1.37, ph=0.036). Our findings provide empirical evidence that ABCB1 C3435T polymorphism may contribute to the risk of MI and ACS, especially among Caucasian populations. Thus, detection of ABCB1 C3435T polymorphism may be a promising biomarker for the early detection of MI and ACS. PMID- 25118985 TI - Titanosaur osteoderms from the Upper Cretaceous of Lo Hueco (Spain) and their implications on the armor of Laurasian titanosaurs. AB - Titanosaurs are the only sauropod dinosaurs known to bear a dermal armor. Their osteoderms are relatively rare finds, with few more than a hundred specimens recovered worldwide. Also, little is known about their intra-individual, intra specific or inter-specific variability. The macrovertebrate site of Lo Hueco (Upper Cretaceous; Cuenca, Spain) has yielded several complete specimens of osteoderms, some associated with fairly articulated specimens. They are all variations of the morphotype known as bulb and root. The presence of only this morphotype in Europe, which is considered as the primitive condition among titanosaurs, seems to indicate that the known Upper Cretaceous Laurasian titanosaurs only bore these referred bulb and root osteoderms. An eliptic Fourier analysis on the outline of complete specimens from this morphotype reveals: i) that they truly are part of a morphological cline; and ii) the existence of a consistent correlation between the outline and the morphology of the bulb. Such variation along a cline is more consistent with intra-individual rather than inter-specific variation. The osteoderms associated with a single titanosaur individual from Lo Hueco reinforce this hypothesis. PMID- 25118984 TI - The gut microbiota and developmental programming of the testis in mice. AB - Nutrients and environmental chemicals, including endocrine disruptors, have been incriminated in the current increase in male reproductive dysfunction, but the underlying mechanisms remain unknown. The gastrointestinal tract represents the largest surface area exposed to our environment and thereby plays a key role in connection with exposure of internal organs to exogenous factors. In this context the gut microbiome (all bacteria and their metabolites) have been shown to be important contributors to body physiology including metabolism, cognitive functions and immunity. Pivotal to male reproduction is a proper development of the testis, including the formation of the blood-testis barrier (BTB) that encapsulates and protects germ cells from stress induced environmental cues, e.g. pathogenic organisms and xenobiotics. Here we used specific pathogen free (SPF) mice and germ-free (GF) mice to explore whether gut microbiota and/or their metabolites can influence testis development and regulation of BTB. Lumen formation in the seminiferous tubules, which coincides with the development of the BTB was delayed in the testes of GF mice at 16 days postpartum. In addition, perfusion experiments (Evans blue) demonstrated increased BTB permeability in these same mice. Reduced expressions of occludin, ZO-2 and E-cadherin in GF testis suggested that the microbiota modulated BTB permeability by regulation of cell-cell adhesion. Interestingly, exposure of GF mice to Clostridium Tyrobutyricum (CBUT), which secrete high levels of butyrate, restored the integrity of the BTB and normalized the levels of cell adhesion proteins. Moreover, the GF mice exhibited lower serum levels of gonadotropins (LH and FSH) than the SPF group. In addition, the intratesticular content of testosterone was lower in GF compared to SPF or CBUT animals. Thus, the gut microbiome can modulate the permeability of the BTB and might play a role in the regulation of endocrine functions of the testis. PMID- 25118987 TI - Effects of ambient temperature on the performance of CCD array spectroradiometers and practical implications for field measurements. AB - The performance of miniature CCD array spectroradiometers, which are widely used for the assessment of personal and environmental exposures, may be affected by variations in ambient temperature. The dark signal, spectral sensitivity and wavelength position of six different array spectroradiometer models, produced by two different manufacturers, were assessed in ambient temperatures ranging from 5 degrees C to 40 degrees C. The results are presented with a discussion of the practical implications for field measurements when the instruments are used outside of a temperature controlled environment. PMID- 25118986 TI - A new basal ankylosaurid (Dinosauria: Ornithischia) from the Lower Cretaceous Jiufotang Formation of Liaoning Province, China. AB - A new ankylosaurid, Chuanqilong chaoyangensis gen. et sp. nov., is described here based on a nearly complete skeleton from the Lower Cretaceous Jiufotang Formation of Baishizui Village, Lingyuan City, Liaoning Province, China. Chuanqilong chaoyangensis can be diagnosed on the basis of two autapomorphies (glenoid fossa for quadrate at same level as the dentary tooth row; distally tapering ischium with constricted midshaft) and also a unique combination of character states (slender, wedge-like lacrimal; long retroarticular process; humerus with strongly expanded proximal end; ratio of humerus to femur length = 0.88). Although a phylogenetic analysis places Chuanqilong chaoyangensis as the sister taxon of the sympatric Liaoningosaurus near the base of the Ankylosauridae, the two taxa can be distinguished on the basis of many features, such as tooth morphology and ischial shape, which are not ontogeny-related. Chuanqilong chaoyangensis represents the fourth ankylosaurid species reported from the Cretaceous of Liaoning, China, suggesting a relatively high diversity in Cretaceous Liaoning. PMID- 25118988 TI - Through a glass darkly: economics and personalised medicine. AB - Personalised medicine and pharmacogenetic-test-guided treatment strategies will be of increasing importance in the future, both in terms of healthcare provision and evaluation. It is well recognised that significant variability exists in the response of patients to drugs resulting from genetic or biological variations; however, we are only now gradually becoming aware of the complexities involved. Enormous variability occurs in the risk-benefit ratio that will be experienced by each individual patient as a consequence of their overall genetic make-up. Although not a panacea, enhanced scientific knowledge of the genetic basis for such variability offers the potential for a more 'tailored' approach to prescribing in the future, making it more closely attuned to the needs of the individual patient. Such 'personalised' medicine has the potential to revolutionise care provision in a manner that provides a range of challenges to current structures and processes of 'conventional' healthcare delivery. The aim of this paper is to outline such challenges and analyse potential ways in which they may be addressed in the future. It provides non-expert readers with a non technical case study of the complexities inherent in the evaluation of a pharmacogenetic-test-guided treatment strategy from a health economic perspective. Wherever possible, technical issues have been minimised; however, references are provided for readers who wish to enhance their knowledge of the pharmacological basis of the case study of cytochrome P450 test-guided treatment. The case study aims simply to illustrate the approach and difficulties encountered in the health economic evaluation of complex pharmacogenetic technologies. Such technologies present a range of new and complex issues which have crucial implications for health economists attempting to obtain an accurate assessment of the 'value' of the technology in clinical practice in an array of patient subgroups. Personalised medicine is the future and this paper highlights how pharmaceutical manufacturers, clinicians, regulators and other stakeholders must all play their part in the inevitable and accelerating move into this complex and uncertain future. PMID- 25118989 TI - A review of approaches for the management of specialty pharmaceuticals in the United States. AB - With increased innovation and development of specialty pharmaceuticals, the US and global healthcare industries are looking to implement appropriate management strategies to control both utilization and costs. Specialty pharmaceuticals are high-cost medications that treat complex, chronic, rare, and difficult-to-manage conditions. These drugs require special drug handling, appropriate clinical outcomes monitoring, and effective cost controls. The primary scope of this article is to discuss various strategies being implemented for specialty pharmaceutical utilization and cost management and correlated outcomes in the USA; these outcomes include enhanced health insurance plan benefit designs with formulary modifications and greater patient cost burden. Additional methods to manage specialty pharmaceuticals include the use of specialty pharmacies for drug distribution, increased emphasis on coordination of care and evidence-based medicine, as well as healthcare reform and regulations. Healthcare spending, both in the US and globally, continues to increase, with a rising proportion of drug spend towards specialty pharmaceuticals. Continued specialty pharmaceutical innovation and introduction of biosimilar products will evolve the currently utilized management strategies for these drugs. PMID- 25118992 TI - Treatment and management of neuromuscular channelopathies. AB - OPINION STATEMENT: Neuromuscular channelopathies are heterogeneous disorders with marked phenotypic and genotypic variability. These include non-dystrophic myotonia (NDM), periodic paralysis (PP), and congenital myasthenic syndrome (CMS). Their diverse clinical manifestations remain a challenge in diagnosis and management to this date. These disorders impact quality of life and cause lifelong disabling symptoms. Treatment options are few and not FDA-approved. This is largely due to a paucity of large, randomized clinical trials in these rare diseases. Challenges of conducting such trials include the rarity of these disorders and the genetic heterogeneity. Physicians rely on off-label use of drugs to treat muscle channelopathies to reduce morbidity and improve quality of life. Besides pharmacological treatment, dietary modifications, lifestyle changes, awareness of triggers, and genetic counseling also play an important role in long-term disease management. This article reviews the current management strategies for neuromuscular channelopathies. PMID- 25118991 TI - Identification of the conserved and novel miRNAs in Mulberry by high-throughput sequencing. AB - miRNAs are a class of non-coding endogenous small RNAs. They play vital roles in plant growth, development, and response to biotic and abiotic stress by negatively regulating genes. Mulberry trees are economically important species with multiple uses. However, to date, little is known about mulberry miRNAs and their target genes. In the present study, three small mulberry RNA libraries were constructed and sequenced using high-throughput sequencing technology. Results showed 85 conserved miRNAs belonging to 31 miRNA families and 262 novel miRNAs at 371 loci. Quantitative real-time PCR (qRT-PCR) analysis confirmed the expression pattern of 9 conserved and 5 novel miRNAs in leaves, bark, and male flowers. A total of 332 potential target genes were predicted to be associated with these 113 novel miRNAs. These results provide a basis for further understanding of mulberry miRNAs and the biological processes in which they are involved. PMID- 25118993 TI - Downregulated CXCL12 expression in mesenchymal stem cells associated with severe aplastic anemia in children. AB - The mechanisms of idiopathic severe aplastic anemia (SAA) in children are not completely understood. Insufficiency of the bone marrow microenvironment, in which mesenchymal stem cells (MSCs) are an important element, can be a potential factor associated with hematopoietic impairment. In the current study, we studied whether aberrant gene expression could be found in MSCs from children with SAA. Using microarray analysis, two different patterns of global gene expression were detected in the SAA MSCs. Fourteen genes (POLE2, HGF, KIF20A, TK1, IL18R1, KITLG, FGF18, RRM2, TTK, CXCL12, DLG7, TOP2A, NUF2, and TYMS), which are related to DNA synthesis, cytokines, or growth factors, were significantly downregulated. Further, knockdown of gene expression was performed using the small hairpin RNA (shRNA)-containing lentivirus method. We found that knockdown of CXCL12, HGF, IL 18R1, FGF18, or RRM2 expression compelled MSCs from the controls to behave like those from the SAA children, with decreased survival and differentiation potential. Among them, inhibition of CXCL12 gene expression had the most profound effects on the behavior of MSCs. Further experiments regarding re-introduction of the CXCL12 gene could largely recover the survival and differentiation potential in MSCs with inhibition of CXCL12 expression. Our findings suggest that MSCs from children with SAA exhibit aberrant gene expression profiles and downregulation of CXCL12 gene may be associated with alterations in the bone marrow microenvironment. PMID- 25118994 TI - CD4+ T cell counts reflect the immunosuppressive state of CD4 helper cells in patients after allogeneic stem cell transplantation. AB - The recovery of the host immune system after allogeneic hematopoietic stem cell transplantation is pivotal to prevent infections, relapse, and secondary malignancies. In particular, numerical CD4+ T cells reconstitution is delayed and CD4 helper cell function is considered impaired as a consequence of the transplant procedure and concomitant immunosuppressive medication. From HIV/AIDS patients, it is known that numerical and functional CD4 defects increase the risk of opportunistic infections. However, and in contrast to patients with HIV, anti infective prophylaxis after allogeneic transplantation is usually given for 6 months depending on immunosuppressive medication and existing graft-versus-host disease but independently of absolute CD4+ T cells counts. We hypothesized that a qualitative T cell defect is existing after allogeneic transplantation, especially in patients with delayed immune-reconstitution. Applying transcriptional as well as functional approaches, we show that CD4+ T cells with delayed recovery have a distinct transcriptional profile and cluster differently from T cells originated from patients with completed immune recovery. Moreover, inhibitory signatures are substantially enriched within the transcriptional profile of these T cells translating to functional defects and impaired interleukin 2 production. In addition to time after transplant, CD4+ T cells numbers should be considered for the decision to stop or maintain antimicrobial prophylaxis in patients after allogeneic stem cell transplantation. PMID- 25118990 TI - Functional interaction between bicarbonate transporters and carbonic anhydrase modulates lactate uptake into mouse cardiomyocytes. AB - Blood-derived lactate is a precious energy substrate for the heart muscle. Lactate is transported into cardiomyocytes via monocarboxylate transporters (MCTs) together with H(+), which couples lactate uptake to cellular pH regulation. In this study, we have investigated how the interplay between different acid/base transporters and carbonic anhydrases (CA), which catalyze the reversible hydration of CO2, modulates the uptake of lactate into isolated mouse cardiomyocytes. Lactate transport was estimated both as lactate-induced acidification and as changes in intracellular lactate levels measured with a newly developed Forster resonance energy transfer (FRET) nanosensor. Recordings of intracellular pH showed an increase in the rate of lactate-induced acidification when CA was inhibited by 6-ethoxy-2-benzothiazolesulfonamide (EZA), while direct measurements of lactate flux demonstrated a decrease in MCT transport activity, when CA was inhibited. The data indicate that catalytic activity of extracellular CA increases lactate uptake and counteracts intracellular lactate-induced acidification. We propose a hypothetical model, in which HCO3 (-), formed from cell-derived CO2 at the outer surface of the cardiomyocyte plasma membrane by membrane-anchored, extracellular CA, is transported into the cell via Na(+)/HCO3 (-) cotransport to counteract intracellular acidification, while the remaining H(+) stabilizes extracellular pH at the surface of the plasma membrane during MCT activity to enhance lactate influx into cardiomyocytes. PMID- 25118995 TI - Influence of TGFB1 C-509T polymorphism on gastric cancer risk associated with TGF beta1 expression in the gastric mucosa. AB - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) has dual roles inhibiting and promoting carcinogenesis. Although many researchers have conducted association studies between TGFB1 C-509T polymorphism and the risk of developing gastric cancer, the results are not uniform. METHODS: We genotyped 1028 gastric cancer patients and 958 controls by the polymerase chain reaction-restriction fragment length polymorphism method. Immunohistochemistry was performed to assess the expression of TGF-beta1 in the cancer and noncancerous tissues of 120 gastric cancer patients. mRNA expression was also measured in noncancerous gastric mucosa by qRT-PCR in the 282 subjects. RESULTS: The CT genotype in the TGFB1 C-509T polymorphism was associated with an increased risk of gastric cancer development (adjusted OR 1.35, 95 % CI 1.07-1.71, P = 0.013), especially for intestinal-type cancer (adjusted OR 1.43, 95 % CI 1.08-1.90, P = 0.014). More frequent TGF-beta1 expression was found in the center of cancer tissue in the TGFB1-509T carrier group than in the others (90.5 % vs. 72.2 %, P = 0.010). T-carriers also presented higher expression level of gastric TGF-beta1 mRNA than non T-carriers (median 1.29 vs. 0.80, P = 0.004) when they were infected by H. pylori. Cancer patients showed elevated gastric TGFB1gene expression compared to the control group (median 1.22 vs. 0.89, P = 0.009). CONCLUSIONS: The carcinogenic effect of TGF-beta1 might be associated with increased gastric TGF-beta1 expression in subjects with the T allele of TGFB1-509. PMID- 25118997 TI - Expression of S6K1 in human visceral adipose tissue is upregulated in obesity and related to insulin resistance and inflammation. AB - The ribosomal protein S6 kinase 1 (S6K1) is a component of the insulin signalling pathway that has been proposed as a key molecular factor in insulin resistance development under conditions of nutrient overload. The aim was to evaluate the involvement of S6K1 in obesity as well as to explore their association with visceral adipose tissue (VAT) inflammation. Samples obtained from 40 subjects were used. Gene expression levels of RPS6KB1 and key inflammatory markers were analysed in VAT. The effect of insulin on transcript levels of RPS6KB1 in human differentiated adipocytes was also explored. RPS6KB1 mRNA levels in VAT were increased (P < 0.05) in obese patients. Insulin treatment significantly enhanced (P < 0.01) gene expression levels of RPS6KB1 and a positive association (P < 0.05) of RPS6KB1 expression with different markers of insulin resistance was observed. Moreover, RPS6KB1 gene expression levels were positively correlated with VAT gene expression levels of the inflammatory markers CCL2, CD68, MMP2, MMP9, VEGFA and CHI3L1 as well as with mRNA levels of MTOR and MAPK8, representative players involved in signalling pathways related to S6K1. The increased levels of S6K1 in obesity and its positive association with insulin resistance and inflammation suggest a role for this protein in the changes that take place in VAT in obesity establishing a link between inflammation and a higher risk for the development of metabolic diseases. PMID- 25118998 TI - Insulin and GH-IGF-I axis: endocrine pacer or endocrine disruptor? AB - Growth hormone/insulin-like growth factor (IGF) axis may play a role in maintaining glucose homeostasis in synergism with insulin. IGF-1 can directly stimulate glucose transport into the muscle through either IGF-1 or insulin/IGF-1 hybrid receptors. In severely decompensated diabetes including diabetic ketoacidosis, plasma levels of IGF-1 are low and insulin delivery into the portal system is required to normalize IGF-1 synthesis and bioavailability. Normalization of serum IGF-1 correlated with the improvement of glucose homeostasis during insulin therapy providing evidence for the use of IGF-1 as biomarker of metabolic control in diabetes. Taking apart the inherent mitogenic discussion, diabetes treatment using insulins with high affinity for the IGF-1 receptor may act as an endocrine pacer exerting a cardioprotective effect by restoring the right level of IGF-1 in bloodstream and target tissues, whereas insulins with low affinity for the IGF-1 receptor may lack this positive effect. An excessive and indirect stimulation of IGF-1 receptor due to sustained and chronic hyperinsulinemia over the therapeutic level required to overtake acute/chronic insulin resistance may act as endocrine disruptor as it may possibly increase the cardiovascular risk in the short and medium term and mitogenic/proliferative action in the long term. In conclusion, normal IGF-1 may be hypothesized to be a good marker of appropriate insulin treatment of the subject with diabetes and may integrate and make more robust the message coming from HbA1c in terms of prediction of cardiovascular risk. PMID- 25118999 TI - Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes. AB - Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 +/- 1.7 years, HbA1c 8.7 +/- 0.2 %, body mass index 24.5 +/- 0.5 kg/m(2)) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor alpha (TNFalpha) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Delta = -68 %, insulin Delta = -58 %, pioglitazone Delta = -49 %). Exenatide reduced VF (Delta = -36 %) and SF (Delta = -13 %), and pioglitazone decreased VF (Delta = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNFalpha (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that DeltaIHF correlated with DeltaHbA1c and Deltaweight. Besides, DeltaIHF correlated with Deltatriglycerides and DeltaTNFalpha, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, DeltaHbA1c alone explained 41.5 % of the variance of DeltaIHF, and DeltaHbA1c + Deltaweight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM. PMID- 25119000 TI - Process and formulation variables of pregabalin microspheres prepared by w/o/o double emulsion solvent diffusion method and their clinical application by animal modeling studies. AB - Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. In conventional therapy recommended dose for pregabalin is 75 mg twice daily or 50 mg three times a day, with maximum dosage of 600 mg/d. To achieve maximum therapeutic effect with a low risk of adverse effects and to reduce often drug dosing, modified release preparations; such as microspheres might be helpful. However, most of the microencapsulation techniques have been used for lipophilic drugs, since hydrophilic drugs like pregabalin, showed low-loading efficiency and rapid dissolution of compounds into the aqueous continous phase. The purpose of this study was to improve loading efficiency of a water-soluble drug and modulate release profiles, and to test the efficiency of the prepared microspheres with the help of animal modeling studies. Pregabalin is a water soluble drug, and it was encapsulated within anionic acrylic resin (Eudragit S 100) microspheres by water in oil in oil (w/o/o) double emulsion solvent diffusion method. Dichloromethane and corn oil were chosen primary and secondary oil phases, respectively. The presence of internal water phase was necessary to form stable emulsion droplets and it accelerated the hardening of microspheres. Tween 80 and Span 80 were used as surfactants to stabilize the water and corn oil phases, respectively. The optimum concentration of Tween 80 was 0.25% (v/v) and Span 80 was 0.02% (v/v). The volume of the continous phase was affected the size of the microspheres. As the volume of the continous phase increased, the size of microspheres decreased. All microsphere formulations were evaluated with the help of in vitro characterization parameters. Microsphere formulations (P1-P5) exhibited entrapment efficiency ranged between 57.00 +/- 0.72 and 69.70 +/- 0.49%; yield ranged between 80.95 +/- 1.21 and 93.05 +/- 1.42%; and mean particle size were between 136.09 +/- 2.57 and 279.09 +/- 1.97 um. Pregabalin microspheres having better results among all formulations (Table 3) were chosen for further studies such as differential scanning calorimetry, Fourier transform infrared analysis and dissolution studies. In the last step, the best pregabalin microsphere formulation (P3) was chosen for in vivo animal studies. The pregabalin-loaded microspheres (P3) and conventional pregabalin capsules were applied orally in rats for three days, resulted in clinical improvement of cold allodynia, an indicator of peripheral neuropathy. This result when evaluated together with the serum pregabalin levels and in vitro release studies suggests that the pregabalin microspheres prepared with w/o/o double emulsion solvent diffusion method can be an alternative form for neuropathic pain therapy. Conclusively, a drug delivery system successfully developed that showed modified release up to 10 h and could be potentially useful to overcome the frequent dosing problems associated with pregabalin conventional dosage form. PMID- 25119003 TI - The role of human papillomavirus infection in the head and neck region and methods for its detection. AB - Human papillomaviruses (HPV) are the etiological factors of many benign and malignant lesions localized in the skin and mucous membranes in the region of the urogenital organs and head and neck. Currently, most assays for the detection of HPV are based on detecting the presence of viral nucleic acids, mostly viral DNA. These molecular techniques can be divided into: 1) methods based on a targeted, selective amplification of nucleic acids, 2) signal amplification methods, 3) nucleic acid hybridization assays. This paper presents and explains a number of different HPV detection methods and provides examples of some commonly available commercial tests. PMID- 25119002 TI - Risk factors for intraocular involvement in patients with primary central nervous system lymphoma. AB - To determine the risk factors for intraocular involvement in patients with primary central nervous system lymphoma (PCNSL), a retrospective chart review was performed on 136 patients who were pathologically diagnosed with PCNSL. The patients were investigated for demographics, clinical manifestation, and the profile of immunohistochemical tumor biomarkers, as well as for the presence of intraocular involvement of lymphoma at diagnosis or during follow-up. The mean age of the entire cohort was 58.6 +/- 12.4 years, and the mean follow-up period was 31.1 +/- 30.8 months. Twenty-nine (21 %) patients had an intraocular involvement, among which 20 (69 %) patients presented with intraocular involvement at diagnosis of PCNSL and 9 (31 %) patients developed intraocular involvement after a mean period of 32.4 +/- 33.6 months. Of the patients with intraocular involvement, 8 (28 %) had no visual symptom at the diagnosis of ocular invasion. Between those with and without intraocular involvement, no significant differences were found with respect to the age, sex, and follow-up period as well as cerebrospinal fluid spread and bone marrow involvement. Among the immunohistochemical biomarkers, the Ki-67 proliferation index was significantly higher in patients with intraocular involvement than in patients without (P = 0.021), but the other investigated biomarkers did not show a significant difference between the two groups. A Ki-67 level >=80 % was a risk factor for the intraocular involvement in patients with PCNSL (odds ratio, 2.63). Median overall survival was 39.0 months in the entire cohort and was not significantly different between those with and without intraocular involvement (P = 0.959). PMID- 25119004 TI - Review of small cell carcinoma of the kidney with focus on clinical and pathobiological aspects. AB - Small cell carcinoma (SmCC) of the kidney is extremely rare. In this article, we present a review of SmCC of the kidney with the focus on clinical and pathobiological aspects. Macroscopically, this tumor often shows a bulky mass extensively replacing the renal parenchyma with vascular invasion and metastasis to lymph nodes. Histologically, the tumor is composed of small cells with scant cytoplasm, round to oval nuclei, finely granular chromatin and inconspicuous nucleoli. Rosette or tubular formation may be present. Immunohistochemically, neoplastic cells show variable positivity for neuron-specific enolase, chromogranin A, synaptophysin, CD57 (Leu7) and CD56. A dot-like staining pattern for cytokeratin may also be observed. An electron microscopic examination may identify electron-dense neurosecretory granules in the cytoplasm. As a therapeutic option, nephrectomy and systemic chemotherapy should be considered. However, despite multimodal therapy, most patients have a dismal outcome and die of widely metastatic disease within one to two years. As there are limited genetic data on SmCC of the kidney, a large series studying this will be needed in the future. PMID- 25119005 TI - Breast pathology after cryotherapy. Histological regression of breast cancer after cryotherapy. AB - A breast saving treatment is contemporary the preferred method of treatment with comparable results in comparing with mastectomy. In this study were evaluated the effects of cryotherapy by histological verification of changes in post treatment resection specimens. Fifty-three patients in age of 38-81 year with histologically confirmed breast cancer in needle biopsies were managed by cryotherapy between 1999 and 2007. The patients were operated between day 1 and 35 after cryotherapy. The histologic examination of operation materials showed in all cases at least partial tumor destruction. In general in 54.7% of all handled cases (29 patient) there was no residual tumor. In 6 cases (22.2%) from group 1 and in 23 cases (88.5%) of group 2 no tumor rest was found. Cryotherapy can lead to complete destruction of tumoral tissue. In our study all 29 (54.7%) of tumor free cases after cryotherapy were those with cT1 stage. The experience of operator and the correct selection of appropriate patients (primarily taking the tumor size into account) play the most important role for achieving the best results. PMID- 25119001 TI - Unyielding progress: recent advances in the treatment of central nervous system neoplasms with radiosurgery and radiation therapy. AB - In the past decade, our understanding of the roles of external beam radiotherapy (EBRT) and stereotactic radiosurgery (SRS) in the management of brain tumors has dramatically improved. To highlight the changes and contemporary treatment approaches, we review the indications and outcomes of ionizing radiation for benign intracranial tumors and brain metastases. For nonfunctioning pituitary adenomas, SRS is able to achieve radiographic tumor control in at least 90 % of cases. The rate of SRS-induced endocrine remission for functioning pituitary adenomas depends on the tumor subtype, but it is generally lower than the rate of radiographic tumor control. The most common complications from pituitary adenoma SRS treatment are hypopituitarism and cranial neuropathies. SRS has become the preferred treatment modality for vestibular schwannomas and skull base meningiomas less than 3 cm in size. Large vestibular schwannomas and meningiomas remain best managed with initial surgical resection or EBRT for surgically ineligible patients. For small to moderately sized brain metastases, there has been a shift toward treatment of newly diagnosed patients with SRS alone due to similar local control rates compared with surgical resection. RCTs have shown combined SRS and whole brain radiation therapy (WBRT) for brain metastases to decrease rates of local and distant intracranial recurrence compared to SRS alone. However, the improved intracranial control comes at the expense of poorer neurocognitive outcomes and without prolonging overall survival. Therefore, WBRT is generally reserved for salvage therapy. While EBRT has been frequently supplanted by SRS for the treatment pituitary adenomas and brain metastases, it still proves useful in selected cases of large lesions which are not amenable to surgical debulking or for those with widespread disease, poor performance status, and short life expectancy. In recent years, the scope of SRS has extended beyond the intracranial space to include extradural and intradural spinal tumors. PMID- 25119006 TI - Selected morphologic features influencing the prognosis of conventional renal cell carcinomas co-expressing P53 and MDM2. AB - Renal cell carcinoma is the most deadly of common urologic malignancies. The classical prognostic factors, including tumor type, grade and stage, as well as performance status of the patient, offer important information, but there is a need for new biomarkers which could improve the quality of prognostication. It has been proposed that tumors co-expressing P53 and MDM2 could represent a specific, more aggressive subgroup. The aim of the study was to explore this hypothesis using tissue microarrays, using two different anti-P53 antibodies. The material analyzed consisted of 470 cases of renal clear cell carcinoma. Reaction for P53 was positive in 15.1 or 13.2% of cases, depending on the antibody used. Reaction for MDM2 was positive in 37.9% of cases; 6.5 or 5.3% of cases coexpressed P53 and MDM2. Both P53-positive and double P53/MDM2-positive cases were higher grade and more likely to contain a sarcomatoid component, but their stage was similar to negative cases. PAb1081 P53-positive MDM2-positive cases were larger than the rest of the tumors (7.6 cm vs. 6.1 cm, p < 0.001). Our data support the hypothesis of prognostic significance of P53, and double P53/MDM2 positivity, yet further studies are needed to clarify the issue. PMID- 25119007 TI - Evaluation of calretinin immunohistochemistry as an additional tool in confirming the diagnosis of Hirschsprung disease. AB - Hirschsprung disease (HD) is a congenital malformation defined as the absence of myenteric and submucosal ganglion cells (GCs) in the distal rectum and variable length of the contiguous bowel. The aim of this study was to assess the utility of calretinin immunochemistry in comparison with that of standard histology complemented with acetylcholinesterase (AChE) histochemistry routinely employed at our institution to evaluate rectal biopsies carried out for suspicion of HD. Twenty-one rectal biopsies were reviewed, including 14 from patients with suspected HD, 6 from infants with necrotizing enterocolitis (NEC), and 1 from a patient diagnosed with spontaneous intestinal perforation (SIP). Sections stained with hematoxylin-eosin (HE) revealed absence of ganglion cells in 13 cases which included 11 patients with HD and 2 patients with NEC. Among 13 cases of aganglionosis the AChE reaction pattern was consistent with HD in 2 patients. Calretinin positivity was observed in all rectal biopsies showing the presence of GC, and the staining was consistently absent in all cases of aganglionosis. In 6 rectal biopsies in which abnormal acetylcholinesterase (AChE) staining was not seen, loss of calretinin immunoreactivity helped establish the diagnosis of HD. PMID- 25119008 TI - Study of nano-hydroxyapatite/zirconia stabilized with yttria in bone healing: histopathological study in rabbit model. AB - Acceleration of bone healing has always been a major challenge in orthopedic surgery, the aim of this study was an evaluation of the biological effects of zirconia-stabilized yttria on bone healing, using an in vivo model. Nano hydroxyapatite powder with zirconia-stabilized yttria were inserted in rabbit tibia and then histologically analyzed and compared with non-treated controls so thirty six. New Zealand white male rabbits randomly divided into two groups of 18 rabbits each. A cortical hole of 4 mm diameter and 8 mm depth in each tibia was drilled. In group I, the defect was left empty, whereas in group II, the bone defect was packed with nano-hydroxyapatite/5% zirconia stabilized with yttria. Histological evaluations were performed at two, four and six weeks after the implantation. Microscopic changes on two groups along with the time course were scored and statistical analysis showed that the average scores in group II were significantly higher than the other groups (p < 0.05). Histological analysis was shown to be significantly improved by the nano-hydroxyapatite/5% zirconia stabilized with yttria compared with the control group, suggesting that this biomaterial promote the healing of cortical bone, presumably by acting as an osteoconductive. PMID- 25119009 TI - The comparison of nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) with Ki67 proliferation marker expression in common skin tumors. AB - Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is a chromosomal protein of unknown function. Its amino acid composition and structure of its DNA binding domain resemble those of high mobility group A (HMGA) proteins which are associated with various malignancies. Since changes in expression of HMGA are considered as a marker of tumor progression, it is possible that similar changes in expression of NUCKS could be a useful tool in diagnosis of malignant skin tumors. To investigate this assumption we used specific antibodies against NUCKS for immunohistochemistry of squamous (SCC) and basal cell carcinoma (BCC) as well as keratoacanthoma (KA). We found high expression of NUCKS in nuclei of SCC and BCC cells which exceeded expression of the well-known proliferation marker Ki67. Expression of NUCKS in benign KA was much below that of malignant tumors. With the present study and based on our previous experience we would like to suggest the NUCKS protein as a novel proliferation marker for immunohistochemical evaluation of formalin-fixed and paraffin-embedded skin tumor specimens. We would like to emphasize that NUCKS abundance in malignant skin tumors is higher than that of the well-known proliferation marker Ki67, thus allowing more precise assessment of tumor proliferation potential. PMID- 25119010 TI - Cadmium in urothelial carcinoma of the bladder. AB - The aim of this study was to examine the relationship between cadmium (Cd) and bladder cancer (urothelial carcinoma of the bladder). Cadmium concentrations in two 36-sample series of bladder cancer tissue and blood, from patients with the neoplasm, were matched with those of the control group. The amount of heavy metal in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median cadmium concentration levels reached statistically lower values in the bladder cancer tissue, as compared with the non-cancer one (11.695 ng/g and 56.32 ng/g respectively, p < 0.001), the median Cd levels in the blood of the patients with this carcinoma showed no statistical difference when compared to those of the control group (8.237 MUg/l and 7.556 MUg/l respectively, p = 0.121). The median levels of cadmium in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p < 0.002 and p < 0.02 respectively). This study has shown that patients with urothelial carcinoma of the bladder had lower tissue cadmium levels than people without tumour while no difference in the Cd blood levels between the two groups of patients under investigation was found. PMID- 25119011 TI - Phosphate nephropathy after administration of bowel purgative containing sodium phosphate - a case report. AB - A 65-year-old woman was admitted to the hospital with an elevated serum creatinine concentration associated with leukocyturia and erythrocyturia. Past medical history analysis revealed that four months before current hospitalization she had been subjected to colonoscopy preceded by the administration of oral sodium phosphate solution (OSP) as preparation for this procedure. Kidney biopsy revealed mild chronic tubulo-interstitial inflammation and scarring with prominent cortical tubular calcium phosphate deposits. The diagnosis of phosphate nephropathy, most probably secondary to OSP ingestion was made. During follow-up the renal function remained impaired but stable with eGFR of 25 ml/min/1.73 m2. The patient is currently under the care of the nephrology clinic. PMID- 25119012 TI - Appearance of estrogen positive bilateral breast carcinoma with HER2 gene amplification in a patient with aplastic anemia. AB - Immunosuppressive therapy is one of the standard therapy protocols for aplastic anemia (AA). However, immunosuppressive therapy and androgenic steroids can promote development of solid tumors such as squamous carcinoma, head and neck tumors, adenocarcinoma of the stomach, hepatocarcinoma and breast carcinoma in long surviving patients with aplastic anemia. We present here a rare case of a 56 year-old woman in whom bilateral adenocarcinoma of the breast developed 11 years after the start of immunosuppressive and androgenic steroid therapy for aplastic anemia. Histological examination showed invasive ductal carcinoma with intense nuclear staining for estrogen receptors. Her2 immunohistochemistry was positive for 80% of stained cells, and chromogenic in situ hybridization showed a high level of HER2 gene amplification. This case indicated that a new therapy option is needed for estimation and evaluation to avoid the consequence of cancer occurrence. PMID- 25119013 TI - Primary mucinous cystadenocarcinoma of the breast with amplification of the HER2 gene confirmed by FISH - case report and review of the literature. AB - Fifty five-years-old woman was presented to the general surgery upon the palpation of a mass in her left breast. In the excisional biopsy performed, partially cystic tumor of 2 * 1 cm with solid areas was macroscopically observed. After through microscopic examination, the patient was diagnosed as invasive mucinous cystadenocarcinoma and the tumor was found to be ER- and PR-negative and C-erbB2 (2+). In the fluorescent in situ hybridization, HER2/neu gene amplification was observed. Here, we present the clinical, cytological, morphological and immunohistochemical features of a very rare type of breast carcinoma, mucinous cystadenocarcinoma of the breast, with the review of the relevant literature. PMID- 25119014 TI - Nested variant of urothelial carcinoma of renal pelvis - a case report. AB - We report a case of an 80-year-old woman with a very rare subtype of urothelial carcinoma - nested variant of urothelial carcinoma mimicking physiological von Brunn's nests. Optimal treatment of NVUC has not been determined due to the small number of cases, as well as the lack of randomized and follow-up studies. In our case the right retroperitoneal nephroureterectomy was chosen. PMID- 25119015 TI - Bilateral pheochromocytoma/intra-adrenal paraganglioma in von Hippel-Lindau patient causing acute myocardial infarction. AB - A 26-year-old male presented to the emergency department complaining of obstipation, severe headache and abdominal pain. An autopsy revealed bilateral pheochromocytoma and acute myocardial infarction. The tumor cells showed positive immunoreactivity of both chromogranin A and synaptophysin and were negative for adrenocortical markers such as SF-1, c17, scc, 3?-HSD as well as SDHB, suggesting a germline mutation of the gene SDHB or SDHD. Molecular genetic analyses did not show a mutation in these two genes, but a mutation in the VHL gene, in exon 3: VHL c.499C>T. This is a missense mutation and causes an amino acid change (Arg167Trp). PMID- 25119016 TI - Hodgkin's lymphoma mimicking tuberculosis in cervical lymph nodes. AB - The authors present a case description of an 81-year-old male with general symptoms (fever, night sweats, weight loss) and cervical/supraclavicular lymphadenopathy. The revised lymph node histopathological examination revealed nodular sclerosis classical Hodgkin's lymphoma associated with abundant tuberculosis-mimicking granulomatous reaction. The diagnosis may be difficult due to similarities in clinical course, laboratory tests and imaging. The morphology of Hodgkin-Reed-Sternberg cells and the immunohistochemical profile are the most helpful in differential diagnosis. In cases where granulomas coexist with negative acid-fast staining, pathologists should always recommend evaluation of further and broader diagnostic procedures to exclude Mycobacterium tuberculosis infection. PMID- 25119017 TI - Breast mass detection using slice conspicuity in 3D reconstructed digital breast volumes. AB - In digital breast tomosynthesis, the three dimensional (3D) reconstructed volumes only provide quasi-3D structure information with limited resolution along the depth direction due to insufficient sampling in depth direction and the limited angular range. The limitation could seriously hamper the conventional 3D image analysis techniques for detecting masses because the limited number of projection views causes blurring in the out-of-focus planes. In this paper, we propose a novel mass detection approach using slice conspicuity in the 3D reconstructed digital breast volumes to overcome the above limitation. First, to overcome the limited resolution along the depth direction, we detect regions of interest (ROIs) on each reconstructed slice and separately utilize the depth directional information to combine the ROIs effectively. Furthermore, we measure the blurriness of each slice for resolving the degradation of performance caused by the blur in the out-of-focus plane. Finally, mass features are extracted from the selected in focus slices and analyzed by a support vector machine classifier to reduce the false positives. Comparative experiments have been conducted on a clinical data set. Experimental results demonstrate that the proposed approach outperforms the conventional 3D approach by achieving a high sensitivity with a small number of false positives. PMID- 25119019 TI - Digital divide 2.0: the role of social networking sites in seeking health information online from a longitudinal perspective. AB - Adopting a longitudinal angle, this study analyzed data from the Pew Internet's Health Tracking Survey in 2006, 2008, and 2010 to identify potential communication inequalities in social networking site use. Results showed that with the growing role of social networking site use in predicting people's likelihood of seeking health information online, the socioeconomic and demographic factors that contributed to the disparities in social networking site use could also lead to disparities in seeking health information online. Also, results indicated that people are more likely to seek heath-related information online if they or their close family or friends have a chronic disease situation. PMID- 25119021 TI - Calcification of arteries supplying the gastric tube: a new risk factor for anastomotic leakage after esophageal surgery. AB - PURPOSE: To evaluate the association between the amount and location of calcifications of the supplying arteries of the gastric tube, as determined with a vascular calcification scoring system, and the occurrence of anastomotic leakage after esophagectomy with gastric tube reconstruction in patients with esophageal cancer. MATERIALS AND METHODS: Institutional review board approval was obtained, and the informed consent requirement was waived for this retrospective study. Consecutive patients who underwent elective esophagectomy for cancer with gastric tube reconstruction and cervical anastomosis between 2003 and 2012 were identified from a prospective database. Vascular calcification scores were retrospectively assigned by reviewing the routine preoperative computed tomographic (CT) images. In patients with anastomotic leakage, presence and severity of calcifications of the aorta (score of 0-2), celiac axis (score of 0 2), right postceliac arteries (common hepatic, gastroduodenal, and right gastroepiploic arteries; score of 0-1), and left postceliac arteries (splenic and left gastroepiploic arteries, score of 0-1) along with patient- and procedure related characteristics were compared with those of patients without leakage by using multivariate logistic regression analysis. RESULTS: Of 246 patients, 58 (24%) experienced anastomotic leakage. No significant differences in patient related factors were found between patients with leakage and those without leakage, with the exception of more chronic use of steroids in the leakage group (7% [four of 58] vs 0% [0 of 188], P = .003). At univariate analysis, leakage was more common in patients with calcification of the aorta (27% [28 of 102] and 35% [13 of 37] vs 16% [17 of 107], P = .029) and the right postceliac arteries (55% [six of 11] vs 22% [52 of 235], P = .013). At multivariate analysis, both minor (odds ratio, 2.00; 95% confidence interval: 1.02, 3.94) and major (odds ratio, 2.87; 95% confidence interval: 1.22, 6.72) aortic calcifications were associated with leakage. Also, an independent association with leakage was found for calcifications of the right postceliac arteries (odds ratio, 4.22; 95% confidence interval: 1.24, 14.4). CONCLUSION: Atherosclerotic calcification of the aorta and right postceliac arteries that supply the gastric tube is an independent risk factor for anastomotic leakage after esophagectomy. PMID- 25119022 TI - Diagnostic utility of second-look US for breast lesions identified at MR imaging: systematic review and meta-analysis. AB - PURPOSE: To evaluate the diagnostic utility of second-look ultrasonography (US) in the assessment of lesions identified at breast magnetic resonance (MR) imaging. MATERIALS AND METHODS: A systematic review of the PubMed database for articles published up to January 6, 2013, was performed by using predefined search terms applied in a standardized manner. Second-look US studies for the assessment of breast lesions identified at MR imaging were eligible for this meta analysis. Two independent reviewers performed the literature review and data extraction. Eligible studies presented data on the number of lesions examined and the number of lesions detected at second-look US. The reference standard for lesion diagnosis was either histopathologic or follow-up examination. Sources of bias were assessed by using the Quality Assessment of Diagnostic Accuracy Studies 2, or QUADAS-2 Quality Assessment of Diagnostic Accuracy Studies 2 , tool. Statistical analysis included data pooling, heterogeneity testing, and meta regression. RESULTS: Seventeen studies that included benign and malignant lesions met the inclusion criteria. The general lesion detection rate at second-look US was very heterogeneous and ranged between 22.6% and 82.1% (pooled rate, 57.5% [1266 of 2201]; 95% confidence interval [ CI confidence interval ]: 50.0%, 64.1% [random-effects model]; I(2) = 90.9%; P < .0001). The highest second-look US detection rates were observed for mass lesions (as opposed to nonmass lesions) and malignant (vs benign) lesions (P < .001 for both). Pooled positive and negative predictive values (positive or negative second-look US correlates of MR imaging-detected malignant or benign lesions) were calculated as 30.7% (95% CI confidence interval : 25.3%, 36.4%; I(2) = 75.4%; P < .0001) and 87.8% (95% CI confidence interval : 82.0%, 92.7%; I(2) = 82.1%; P < .0001), respectively, by using random-effects models. CONCLUSION: The results of this study demonstrated variable utility of second-look US in MR imaging-detected lesions, as lesion detection rates were very heterogeneous. Subgroup analysis showed that malignant and mass lesions were more likely to be detected at second-look US. Furthermore, malignancy was not excluded if a lesion was not detected at second-look US. PMID- 25119020 TI - Biallelic alterations of the large tumor suppressor 1 (LATS1) gene in infiltrative, but not superficial, basal cell carcinomas in a Japanese patient with nevoid basal cell carcinoma syndrome. AB - The present study was conducted to address the molecular pathogenesis underlying the progression of basal cell carcinoma (BCC) in a nevoid basal cell carcinoma syndrome (NBCCS) patient. We analyzed infiltrative BCCs that invaded the subcutaneous tissue of the scalp and penetrated the skull in a 61-year-old Japanese female. Whole-exome sequencing validated by Sanger sequencing was applied to assess the subcutaneously infiltrative BCCs. Differences in genetic alterations between the superficial and infiltrative BCCs were also examined. Of particular note, the infiltrative BCCs showed a nonsense mutation, c.943C>T, resulting in p.Q315X in the large tumor suppressor 1 (LATS1) gene, as well as the loss of the wild-type allele of LATS1 (6q25.1), thus indicating that the LATS1 gene was biallelically disrupted. In contrast, no alterations in the LATS1 gene were observed in the superficial BCCs. Additionally, a loss of heterozygosity analysis revealed that the distal region of chromosome 6q where LATS1 locates was deleted in a heterozygous manner. The present results imply that the biallelic disruption of LATS1 is a progressive factor of the infiltrative BCCs observed in this NBCCS patient and suggest that the Hippo pathway is a potential therapeutic target in cases of infiltrative BCC. PMID- 25119018 TI - Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma. AB - The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+) T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms. PMID- 25119023 TI - Crossed cerebellar diaschisis due to cerebral diffuse large B cell lymphoma on 18F-FDG PET/CT. PMID- 25119024 TI - Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in western countries, with a median survival of 6 months and an extremely low percentage of long-term surviving patients. KRAS mutations are known to be a driver event of PDAC, but targeting mutant KRAS has proved challenging. Targeting oncogene-driven signalling pathways is a clinically validated approach for several devastating diseases. Still, despite marked tumour shrinkage, the frequency of relapse indicates that a fraction of tumour cells survives shut down of oncogenic signalling. Here we explore the role of mutant KRAS in PDAC maintenance using a recently developed inducible mouse model of mutated Kras (Kras(G12D), herein KRas) in a p53(LoxP/WT) background. We demonstrate that a subpopulation of dormant tumour cells surviving oncogene ablation (surviving cells) and responsible for tumour relapse has features of cancer stem cells and relies on oxidative phosphorylation for survival. Transcriptomic and metabolic analyses of surviving cells reveal prominent expression of genes governing mitochondrial function, autophagy and lysosome activity, as well as a strong reliance on mitochondrial respiration and a decreased dependence on glycolysis for cellular energetics. Accordingly, surviving cells show high sensitivity to oxidative phosphorylation inhibitors, which can inhibit tumour recurrence. Our integrated analyses illuminate a therapeutic strategy of combined targeting of the KRAS pathway and mitochondrial respiration to manage pancreatic cancer. PMID- 25119025 TI - Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway. AB - The pluripotency factor Lin28 inhibits the biogenesis of the let-7 family of mammalian microRNAs. Lin28 is highly expressed in embryonic stem cells and has a fundamental role in regulation of development, glucose metabolism and tissue regeneration. Overexpression of Lin28 is correlated with the onset of numerous cancers, whereas let-7, a tumour suppressor, silences several human oncogenes. Lin28 binds to precursor let-7 (pre-let-7) hairpins, triggering the 3' oligo uridylation activity of TUT4 and TUT7 (refs 10-12). The oligoU tail added to pre let-7 serves as a decay signal, as it is rapidly degraded by Dis3l2 (refs 13, 14), a homologue of the catalytic subunit of the RNA exosome. The molecular basis of Lin28-mediated recruitment of TUT4 and TUT7 to pre-let-7 and its subsequent degradation by Dis3l2 is largely unknown. To examine the mechanism of Dis3l2 substrate recognition we determined the structure of mouse Dis3l2 in complex with an oligoU RNA to mimic the uridylated tail of pre-let-7. Three RNA-binding domains form an open funnel on one face of the catalytic domain that allows RNA to navigate a path to the active site different from that of its exosome counterpart. The resulting path reveals an extensive network of uracil-specific interactions spanning the first 12 nucleotides of an oligoU-tailed RNA. We identify three U-specificity zones that explain how Dis3l2 recognizes, binds and processes uridylated pre-let-7 in the final step of the Lin28-let-7 pathway. PMID- 25119029 TI - Earth science: Warning signs of the Iquique earthquake. PMID- 25119027 TI - Abrupt glacial climate shifts controlled by ice sheet changes. AB - During glacial periods of the Late Pleistocene, an abundance of proxy data demonstrates the existence of large and repeated millennial-scale warming episodes, known as Dansgaard-Oeschger (DO) events. This ubiquitous feature of rapid glacial climate change can be extended back as far as 800,000 years before present (BP) in the ice core record, and has drawn broad attention within the science and policy-making communities alike. Many studies have been dedicated to investigating the underlying causes of these changes, but no coherent mechanism has yet been identified. Here we show, by using a comprehensive fully coupled model, that gradual changes in the height of the Northern Hemisphere ice sheets (NHISs) can alter the coupled atmosphere-ocean system and cause rapid glacial climate shifts closely resembling DO events. The simulated global climate responses--including abrupt warming in the North Atlantic, a northward shift of the tropical rainbelts, and Southern Hemisphere cooling related to the bipolar seesaw--are generally consistent with empirical evidence. As a result of the coexistence of two glacial ocean circulation states at intermediate heights of the ice sheets, minor changes in the height of the NHISs and the amount of atmospheric CO2 can trigger the rapid climate transitions via a local positive atmosphere-ocean-sea-ice feedback in the North Atlantic. Our results, although based on a single model, thus provide a coherent concept for understanding the recorded millennial-scale variability and abrupt climate changes in the coupled atmosphere-ocean system, as well as their linkages to the volume of the intermediate ice sheets during glacials. PMID- 25119028 TI - Continuing megathrust earthquake potential in Chile after the 2014 Iquique earthquake. AB - The seismic gap theory identifies regions of elevated hazard based on a lack of recent seismicity in comparison with other portions of a fault. It has successfully explained past earthquakes (see, for example, ref. 2) and is useful for qualitatively describing where large earthquakes might occur. A large earthquake had been expected in the subduction zone adjacent to northern Chile, which had not ruptured in a megathrust earthquake since a M ~8.8 event in 1877. On 1 April 2014 a M 8.2 earthquake occurred within this seismic gap. Here we present an assessment of the seismotectonics of the March-April 2014 Iquique sequence, including analyses of earthquake relocations, moment tensors, finite fault models, moment deficit calculations and cumulative Coulomb stress transfer. This ensemble of information allows us to place the sequence within the context of regional seismicity and to identify areas of remaining and/or elevated hazard. Our results constrain the size and spatial extent of rupture, and indicate that this was not the earthquake that had been anticipated. Significant sections of the northern Chile subduction zone have not ruptured in almost 150 years, so it is likely that future megathrust earthquakes will occur to the south and potentially to the north of the 2014 Iquique sequence. PMID- 25119026 TI - Noncoding RNA transcription targets AID to divergently transcribed loci in B cells. AB - The vast majority of the mammalian genome has the potential to express noncoding RNA (ncRNA). The 11-subunit RNA exosome complex is the main source of cellular 3' 5' exoribonucleolytic activity and potentially regulates the mammalian noncoding transcriptome. Here we generated a mouse model in which the essential subunit Exosc3 of the RNA exosome complex can be conditionally deleted. Exosc3-deficient B cells lack the ability to undergo normal levels of class switch recombination and somatic hypermutation, two mutagenic DNA processes used to generate antibody diversity via the B-cell mutator protein activation-induced cytidine deaminase (AID). The transcriptome of Exosc3-deficient B cells has revealed the presence of many novel RNA exosome substrate ncRNAs. RNA exosome substrate RNAs include xTSS RNAs, transcription start site (TSS)-associated antisense transcripts that can exceed 500 base pairs in length and are transcribed divergently from cognate coding gene transcripts. xTSS-RNAs are most strongly expressed at genes that accumulate AID-mediated somatic mutations and/or are frequent translocation partners of DNA double-strand breaks generated at Igh in B cells. Strikingly, translocations near TSSs or within gene bodies occur over regions of RNA exosome substrate ncRNA expression. These RNA exosome-regulated, antisense-transcribed regions of the B-cell genome recruit AID and accumulate single-strand DNA structures containing RNA-DNA hybrids. We propose that RNA exosome regulation of ncRNA recruits AID to single-strand DNA-forming sites of antisense and divergent transcription in the B-cell genome, thereby creating a link between ncRNA transcription and overall maintenance of B-cell genomic integrity. PMID- 25119030 TI - Developmental biology: It takes muscle to make blood cells. PMID- 25119031 TI - Immunology: Mammalian watchdog targets bacteria. PMID- 25119032 TI - Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates. AB - Mammalian cells possess mechanisms to detect and defend themselves from invading viruses. In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection. Detection triggers a signalling cascade via the adaptor MAVS that culminates in the production of type I interferons (IFN-alpha and beta; hereafter IFN), which are key antiviral cytokines. RIG-I and MDA5 are activated by distinct viral RNA structures and much evidence indicates that RIG-I responds to RNAs bearing a triphosphate (ppp) moiety in conjunction with a blunt-ended, base-paired region at the 5'-end (reviewed in refs 1, 2, 3). Here we show that RIG-I also mediates antiviral responses to RNAs bearing 5'-diphosphates (5'pp). Genomes from mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yeast L-A virus, and base-paired 5'pp-RNAs made by in vitro transcription or chemical synthesis, all bind to RIG-I and serve as RIG-I agonists. Furthermore, a RIG-I-dependent response to 5'pp-RNA is essential for controlling reovirus infection in cultured cells and in mice. Thus, the minimal determinant for RIG-I recognition is a base paired RNA with 5'pp. Such RNAs are found in some viruses but not in uninfected cells, indicating that recognition of 5'pp-RNA, like that of 5'ppp-RNA, acts as a powerful means of self/non-self discrimination by the innate immune system. PMID- 25119033 TI - Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. AB - To protect against human immunodeficiency virus (HIV-1) infection, broadly neutralizing antibodies (bnAbs) must be active at the portals of viral entry in the gastrointestinal or cervicovaginal tracts. The localization and persistence of antibodies at these sites is influenced by the neonatal Fc receptor (FcRn), whose role in protecting against infection in vivo has not been defined. Here, we show that a bnAb with enhanced FcRn binding has increased gut mucosal tissue localization, which improves protection against lentiviral infection in non-human primates. A bnAb directed to the CD4-binding site of the HIV-1 envelope (Env) protein (denoted VRC01) was modified by site-directed mutagenesis to increase its binding affinity for FcRn. This enhanced FcRn-binding mutant bnAb, denoted VRC01 LS, displayed increased transcytosis across human FcRn-expressing cellular monolayers in vitro while retaining FcgammaRIIIa binding and function, including antibody-dependent cell-mediated cytotoxicity (ADCC) activity, at levels similar to VRC01 (the wild type). VRC01-LS had a threefold longer serum half-life than VRC01 in non-human primates and persisted in the rectal mucosa even when it was no longer detectable in the serum. Notably, VRC01-LS mediated protection superior to that afforded by VRC01 against intrarectal infection with simian-human immunodeficiency virus (SHIV). These findings suggest that modification of FcRn binding provides a mechanism not only to increase serum half-life but also to enhance mucosal localization that confers immune protection. Mutations that enhance FcRn function could therefore increase the potency and durability of passive immunization strategies to prevent HIV-1 infection. PMID- 25119034 TI - Inflammatory caspases are innate immune receptors for intracellular LPS. AB - The murine caspase-11 non-canonical inflammasome responds to various bacterial infections. Caspase-11 activation-induced pyroptosis, in response to cytoplasmic lipopolysaccharide (LPS), is critical for endotoxic shock in mice. The mechanism underlying cytosolic LPS sensing and the responsible pattern recognition receptor are unknown. Here we show that human monocytes, epithelial cells and keratinocytes undergo necrosis upon cytoplasmic delivery of LPS. LPS-induced cytotoxicity was mediated by human caspase-4 that could functionally complement murine caspase-11. Human caspase-4 and the mouse homologue caspase-11 (hereafter referred to as caspase-4/11) and also human caspase-5, directly bound to LPS and lipid A with high specificity and affinity. LPS associated with endogenous caspase-11 in pyroptotic cells. Insect-cell purified caspase-4/11 underwent oligomerization upon LPS binding, resulting in activation of the caspases. Underacylated lipid IVa and lipopolysaccharide from Rhodobacter sphaeroides (LPS RS) could bind to caspase-4/11 but failed to induce their oligomerization and activation. LPS binding was mediated by the CARD domain of the caspase. Binding deficient CARD-domain point mutants did not respond to LPS with oligomerization or activation and failed to induce pyroptosis upon LPS electroporation or bacterial infections. The function of caspase-4/5/11 represents a new mode of pattern recognition in immunity and also an unprecedented means of caspase activation. PMID- 25119035 TI - Piezo1 integration of vascular architecture with physiological force. AB - The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca(2+)-permeable non selective cationic channels for detection of noxious mechanical impact. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology. PMID- 25119036 TI - Required enhancer-matrin-3 network interactions for a homeodomain transcription program. AB - Homeodomain proteins, described 30 years ago, exert essential roles in development as regulators of target gene expression; however, the molecular mechanisms underlying transcriptional activity of homeodomain factors remain poorly understood. Here investigation of a developmentally required POU homeodomain transcription factor, Pit1 (also known as Pou1f1), has revealed that, unexpectedly, binding of Pit1-occupied enhancers to a nuclear matrin-3-rich network/architecture is a key event in effective activation of the Pit1-regulated enhancer/coding gene transcriptional program. Pit1 association with Satb1 (ref. 8) and beta-catenin is required for this tethering event. A naturally occurring, dominant negative, point mutation in human PIT1(R271W), causing combined pituitary hormone deficiency, results in loss of Pit1 association with beta catenin and Satb1 and therefore the matrin-3-rich network, blocking Pit1 dependent enhancer/coding target gene activation. This defective activation can be rescued by artificial tethering of the mutant R271W Pit1 protein to the matrin 3 network, bypassing the pre-requisite association with beta-catenin and Satb1 otherwise required. The matrin-3 network-tethered R271W Pit1 mutant, but not the untethered protein, restores Pit1-dependent activation of the enhancers and recruitment of co-activators, exemplified by p300, causing both enhancer RNA transcription and target gene activation. These studies have thus revealed an unanticipated homeodomain factor/beta-catenin/Satb1-dependent localization of target gene regulatory enhancer regions to a subnuclear architectural structure that serves as an underlying mechanism by which an enhancer-bound homeodomain factor effectively activates developmental gene transcriptional programs. PMID- 25119037 TI - Inappropriate p53 activation during development induces features of CHARGE syndrome. AB - CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood. Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p53(25,26,53,54)), along with a wild-type allele of p53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p53(25,26,53,54) mutant protein stabilized and hyperactivated wild-type p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p53(25,26,53,54)(/-) embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regulating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome. PMID- 25119040 TI - Interacting supernovae from photoionization-confined shells around red supergiant stars. AB - Betelgeuse, a nearby red supergiant, is a fast-moving star with a powerful stellar wind that drives a bow shock into its surroundings. This picture has been challenged by the discovery of a dense and almost static shell that is three times closer to the star than the bow shock and has been decelerated by some external force. The two physically distinct structures cannot both be formed by the hydrodynamic interaction of the wind with the interstellar medium. Here we report that a model in which Betelgeuse's wind is photoionized by radiation from external sources can explain the static shell without requiring a new understanding of the bow shock. Pressure from the photoionized wind generates a standing shock in the neutral part of the wind and forms an almost static, photoionization-confined shell. Other red supergiants should have much more massive shells than Betelgeuse, because the photoionization-confined shell traps up to 35 per cent of all mass lost during the red supergiant phase, confining this gas close to the star until it explodes. After the supernova explosion, massive shells dramatically affect the supernova light curve, providing a natural explanation for the many supernovae that have signatures of circumstellar interaction. PMID- 25119039 TI - Structural mechanism of glutamate receptor activation and desensitization. AB - Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the vertebrate brain. To gain a better understanding of how structural changes gate ion flux across the membrane, we trapped rat AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and kainate receptor subtypes in their major functional states and analysed the resulting structures using cryo-electron microscopy. We show that transition to the active state involves a 'corkscrew' motion of the receptor assembly, driven by closure of the ligand-binding domain. Desensitization is accompanied by disruption of the amino-terminal domain tetramer in AMPA, but not kainate, receptors with a two-fold to four-fold symmetry transition in the ligand-binding domains in both subtypes. The 7.6 A structure of a desensitized kainate receptor shows how these changes accommodate channel closing. These findings integrate previous physiological, biochemical and structural analyses of glutamate receptors and provide a molecular explanation for key steps in receptor gating. PMID- 25119038 TI - AhR sensing of bacterial pigments regulates antibacterial defence. AB - The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that senses environmental toxins and endogenous ligands, thereby inducing detoxifying enzymes and modulating immune cell differentiation and responses. We hypothesized that AhR evolved to sense not only environmental pollutants but also microbial insults. We characterized bacterial pigmented virulence factors, namely the phenazines from Pseudomonas aeruginosa and the naphthoquinone phthiocol from Mycobacterium tuberculosis, as ligands of AhR. Upon ligand binding, AhR activation leads to virulence factor degradation and regulated cytokine and chemokine production. The relevance of AhR to host defence is underlined by heightened susceptibility of AhR-deficient mice to both P. aeruginosa and M. tuberculosis. Thus, we demonstrate that AhR senses distinct bacterial virulence factors and controls antibacterial responses, supporting a previously unidentified role for AhR as an intracellular pattern recognition receptor, and identify bacterial pigments as a new class of pathogen-associated molecular patterns. PMID- 25119041 TI - Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes. AB - The connection between an altered gut microbiota and metabolic disorders such as obesity, diabetes, and cardiovascular disease is well established. Defects in preserving the integrity of the mucosal barriers can result in systemic endotoxaemia that contributes to chronic low-grade inflammation, which further promotes the development of metabolic syndrome. Interleukin (IL)-22 exerts essential roles in eliciting antimicrobial immunity and maintaining mucosal barrier integrity within the intestine. Here we investigate the connection between IL-22 and metabolic disorders. We find that the induction of IL-22 from innate lymphoid cells and CD4(+) T cells is impaired in obese mice under various immune challenges, especially in the colon during infection with Citrobacter rodentium. While innate lymphoid cell populations are largely intact in obese mice, the upregulation of IL-23, a cytokine upstream of IL-22, is compromised during the infection. Consequently, these mice are susceptible to C. rodentium infection, and both exogenous IL-22 and IL-23 are able to restore the mucosal host defence. Importantly, we further unveil unexpected functions of IL-22 in regulating metabolism. Mice deficient in IL-22 receptor and fed with high-fat diet are prone to developing metabolic disorders. Strikingly, administration of exogenous IL-22 in genetically obese leptin-receptor-deficient (db/db) mice and mice fed with high-fat diet reverses many of the metabolic symptoms, including hyperglycaemia and insulin resistance. IL-22 shows diverse metabolic benefits, as it improves insulin sensitivity, preserves gut mucosal barrier and endocrine functions, decreases endotoxaemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. In summary, we identify the IL-22 pathway as a novel target for therapeutic intervention in metabolic diseases. PMID- 25119042 TI - PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4 based therapies. AB - The polycomb repressive complex 2 (PRC2) exerts oncogenic effects in many tumour types. However, loss-of-function mutations in PRC2 components occur in a subset of haematopoietic malignancies, suggesting that this complex plays a dichotomous and poorly understood role in cancer. Here we provide genomic, cellular, and mouse modelling data demonstrating that the polycomb group gene SUZ12 functions as tumour suppressor in PNS tumours, high-grade gliomas and melanomas by cooperating with mutations in NF1. NF1 encodes a Ras GTPase-activating protein (RasGAP) and its loss drives cancer by activating Ras. We show that SUZ12 loss potentiates the effects of NF1 mutations by amplifying Ras-driven transcription through effects on chromatin. Importantly, however, SUZ12 inactivation also triggers an epigenetic switch that sensitizes these cancers to bromodomain inhibitors. Collectively, these studies not only reveal an unexpected connection between the PRC2 complex, NF1 and Ras, but also identify a promising epigenetic based therapeutic strategy that may be exploited for a variety of cancers. PMID- 25119043 TI - Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1. AB - Haematopoietic stem cells (HSCs) are self-renewing stem cells capable of replenishing all blood lineages. In all vertebrate embryos that have been studied, definitive HSCs are generated initially within the dorsal aorta (DA) of the embryonic vasculature by a series of poorly understood inductive events. Previous studies have identified that signalling relayed from adjacent somites coordinates HSC induction, but the nature of this signal has remained elusive. Here we reveal that somite specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the zebrafish somite that we have defined as the endotome. Endothelial cells of the endotome are specified within the nascent somite by the activity of the homeobox gene meox1. Specified endotomal cells consequently migrate and colonize the DA, where they induce HSC formation through the deployment of chemokine signalling activated in these cells during endotome formation. Loss of meox1 activity expands the endotome at the expense of a second somitic cell type, the muscle precursors of the dermomyotomal equivalent in zebrafish, the external cell layer. The resulting increase in endotome-derived cells that migrate to colonize the DA generates a dramatic increase in chemokine-dependent HSC induction. This study reveals the molecular basis for a novel somite lineage restriction mechanism and defines a new paradigm in induction of definitive HSCs. PMID- 25119044 TI - CRISPR-mediated direct mutation of cancer genes in the mouse liver. AB - The study of cancer genes in mouse models has traditionally relied on genetically engineered strains made via transgenesis or gene targeting in embryonic stem cells. Here we describe a new method of cancer model generation using the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR associated proteins) system in vivo in wild-type mice. We used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs) to the liver that directly target the tumour suppressor genes Pten (ref. 5) and p53 (also known as TP53 and Trp53) (ref. 6), alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology. Simultaneous targeting of Pten and p53 induced liver tumours that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumour tissue revealed insertion or deletion mutations of the tumour suppressor genes, including bi-allelic mutations of both Pten and p53 in tumours. Furthermore, co-injection of Cas9 plasmids harbouring sgRNAs targeting the beta-catenin gene and a single-stranded DNA oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of beta-catenin. This study demonstrates the feasibility of direct mutation of tumour suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics. PMID- 25119046 TI - Promoter sequences direct cytoplasmic localization and translation of mRNAs during starvation in yeast. AB - A universal feature of the response to stress and nutrient limitation is transcriptional upregulation of genes that encode proteins important for survival. Under many such conditions, the overall protein synthesis level is reduced, thereby dampening the stress response at the level of protein expression. For example, during glucose starvation in Saccharomyces cerevisiae (yeast), translation is rapidly repressed, yet the transcription of many stress- and glucose-repressed genes is increased. Here we show, using ribosomal profiling and microscopy, that this transcriptionally upregulated gene set consists of two classes: one class produces messenger RNAs that are translated during glucose starvation and are diffusely localized in the cytoplasm, including many heat shock protein mRNAs; and the other class produces mRNAs that are not efficiently translated during glucose starvation and are concentrated in foci that co localize with P bodies and stress granules, a class that is enriched for mRNAs involved in glucose metabolism. Surprisingly, the information specifying the differential localization and protein production of these two classes of mRNA is encoded in the promoter sequence: promoter responsiveness to heat-shock factor 1 (Hsf1) specifies diffuse cytoplasmic localization and higher protein production on glucose starvation. Thus, promoter sequences can influence not only the levels of mRNAs but also the subcellular localization of mRNAs and the efficiency with which they are translated, enabling cells to tailor protein production to the environmental conditions. PMID- 25119045 TI - A long noncoding RNA protects the heart from pathological hypertrophy. AB - The role of long noncoding RNA (lncRNA) in adult hearts is unknown; also unclear is how lncRNA modulates nucleosome remodelling. An estimated 70% of mouse genes undergo antisense transcription, including myosin heavy chain 7 (Myh7), which encodes molecular motor proteins for heart contraction. Here we identify a cluster of lncRNA transcripts from Myh7 loci and demonstrate a new lncRNA chromatin mechanism for heart failure. In mice, these transcripts, which we named myosin heavy-chain-associated RNA transcripts (Myheart, or Mhrt), are cardiac specific and abundant in adult hearts. Pathological stress activates the Brg1 Hdac-Parp chromatin repressor complex to inhibit Mhrt transcription in the heart. Such stress-induced Mhrt repression is essential for cardiomyopathy to develop: restoring Mhrt to the pre-stress level protects the heart from hypertrophy and failure. Mhrt antagonizes the function of Brg1, a chromatin-remodelling factor that is activated by stress to trigger aberrant gene expression and cardiac myopathy. Mhrt prevents Brg1 from recognizing its genomic DNA targets, thus inhibiting chromatin targeting and gene regulation by Brg1. It does so by binding to the helicase domain of Brg1, a domain that is crucial for tethering Brg1 to chromatinized DNA targets. Brg1 helicase has dual nucleic-acid-binding specificities: it is capable of binding lncRNA (Mhrt) and chromatinized--but not naked--DNA. This dual-binding feature of helicase enables a competitive inhibition mechanism by which Mhrt sequesters Brg1 from its genomic DNA targets to prevent chromatin remodelling. A Mhrt-Brg1 feedback circuit is thus crucial for heart function. Human MHRT also originates from MYH7 loci and is repressed in various types of myopathic hearts, suggesting a conserved lncRNA mechanism in human cardiomyopathy. Our studies identify a cardioprotective lncRNA, define a new targeting mechanism for ATP-dependent chromatin-remodelling factors, and establish a new paradigm for lncRNA-chromatin interaction. PMID- 25119047 TI - Jam1a-Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling. AB - Notch signalling plays a key role in the generation of haematopoietic stem cells (HSCs) during vertebrate development and requires intimate contact between signal emitting and signal-receiving cells, although little is known regarding when, where and how these intercellular events occur. We previously reported that the somitic Notch ligands, Dlc and Dld, are essential for HSC specification. It has remained unclear, however, how these somitic requirements are connected to the later emergence of HSCs from the dorsal aorta. Here we show in zebrafish that Notch signalling establishes HSC fate as their shared vascular precursors migrate across the ventral face of the somite and that junctional adhesion molecules (JAMs) mediate this required Notch signal transduction. HSC precursors express jam1a (also known as f11r) and migrate axially across the ventral somite, where Jam2a and the Notch ligands Dlc and Dld are expressed. Despite no alteration in the expression of Notch ligand or receptor genes, loss of function of jam1a led to loss of Notch signalling and loss of HSCs. Enforced activation of Notch in shared vascular precursors rescued HSCs in jam1a or jam2a deficient embryos. Together, these results indicate that Jam1a-Jam2a interactions facilitate the transduction of requisite Notch signals from the somite to the precursors of HSCs, and that these events occur well before formation of the dorsal aorta. PMID- 25119049 TI - Gradual unlocking of plate boundary controlled initiation of the 2014 Iquique earthquake. AB - On 1 April 2014, Northern Chile was struck by a magnitude 8.1 earthquake following a protracted series of foreshocks. The Integrated Plate Boundary Observatory Chile monitored the entire sequence of events, providing unprecedented resolution of the build-up to the main event and its rupture evolution. Here we show that the Iquique earthquake broke a central fraction of the so-called northern Chile seismic gap, the last major segment of the South American plate boundary that had not ruptured in the past century. Since July 2013 three seismic clusters, each lasting a few weeks, hit this part of the plate boundary with earthquakes of increasing peak magnitudes. Starting with the second cluster, geodetic observations show surface displacements that can be associated with slip on the plate interface. These seismic clusters and their slip transients occupied a part of the plate interface that was transitional between a fully locked and a creeping portion. Leading up to this earthquake, the b value of the foreshocks gradually decreased during the years before the earthquake, reversing its trend a few days before the Iquique earthquake. The mainshock finally nucleated at the northern end of the foreshock area, which skirted a locked patch, and ruptured mainly downdip towards higher locking. Peak slip was attained immediately downdip of the foreshock region and at the margin of the locked patch. We conclude that gradual weakening of the central part of the seismic gap accentuated by the foreshock activity in a zone of intermediate seismic coupling was instrumental in causing final failure, distinguishing the Iquique earthquake from most great earthquakes. Finally, only one-third of the gap was broken and the remaining locked segments now pose a significant, increased seismic hazard with the potential to host an earthquake with a magnitude of >8.5. PMID- 25119048 TI - X-ray structure of the mouse serotonin 5-HT3 receptor. AB - Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast neurotransmission throughout the nervous system. The molecular processes of neurotransmitter binding, subsequent opening of the ion channel and ion permeation remain poorly understood. Here we present the X-ray structure of a mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 A resolution. The structure of the proteolysed receptor, made up of two fragments and comprising part of the intracellular domain, was determined in complex with stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of the neurotransmitter binding site capped by a nanobody. The membrane domain delimits an aqueous pore with a 4.6 A constriction. In the intracellular domain, a bundle of five intracellular helices creates a closed vestibule where lateral portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of the intracellular domain, expands the structural basis for understanding the operating mechanism of mammalian Cys-loop receptors. PMID- 25119051 TI - Comment on: editorial by Husted et al. "Non-vitamin K antagonist oral anticoagulants (NOACs): no longer new or novel". (Thromb Haemost 2014; 111: 781 782). PMID- 25119050 TI - Protein competition switches the function of COP9 from self-renewal to differentiation. AB - The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals. In the Drosophila melanogaster ovary, some intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others stimulate differentiation. However, it remains poorly understood how the balance between self-renewal and differentiation is controlled. Here we use D. melanogaster ovarian GSCs to demonstrate that the differentiation factor Bam controls the functional switch of the COP9 complex from self-renewal to differentiation via protein competition. The COP9 complex is composed of eight Csn subunits, Csn1-8, and removes Nedd8 modifications from target proteins. Genetic results indicated that the COP9 complex is required intrinsically for GSC self-renewal, whereas other Csn proteins, with the exception of Csn4, were also required for GSC progeny differentiation. Bam-mediated Csn4 sequestration from the COP9 complex via protein competition inactivated the self-renewing function of COP9 and allowed other Csn proteins to promote GSC differentiation. Therefore, this study reveals a protein-competition-based mechanism for controlling the balance between stem cell self-renewal and differentiation. Because numerous self renewal factors are ubiquitously expressed throughout the stem cell lineage in various systems, protein competition may function as an important mechanism for controlling the self-renewal-to-differentiation switch. PMID- 25119052 TI - Does proximal tibial osteotomy with a novel osteotomy system obtain coronal plane correction without affecting tibial slope and patellar height? AB - PURPOSE: To determine changes in tibial slope, patellar height, and coronal plane alignment after medial opening wedge proximal tibial osteotomy (PTO) using a modern osteotomy system. METHODS: Patients undergoing medial opening wedge PTO for any indication with follow-up until radiographic union were identified. Pre- and post-operative tibial slope (referenced off the anterior tibial cortex, proximal tibial anatomic axis, and posterior tibial cortex), patellar height (Caton-Deschamps, Blackburne-Peel, and Insall-Salvati indices), and coronal plane [mechanical axis and weight-bearing line (WBL) ratio] measurements were taken by two observers and compared. RESULTS: Review of 27 patients demonstrated unchanged tibial slope and slightly decreased patellar height post-operatively (Caton Deschamps: -0.10 +/- 0.09; Blackburne-Peel: -0.11 +/- 0.10). Coronal plane measurements showed 6.4 degrees +/- 1.8 degrees mean change in mechanical axis. Mean post-operative WBL ratio was significantly lower (51.6 +/- 11.5 %) than mean goal WBL ratio (62.2 +/- 2.5 %). Preoperative mechanical axis >6 degrees varus and osteoarthritis alone as the surgical indication were risk factors for undercorrection >10 %. CONCLUSIONS: Medial opening wedge PTO using a recently developed instrumentation system was found to have no effect on tibial slope. Patellar height was decreased after osteotomy using this system, although clinical significance of these findings is unknown. Coronal plane undercorrection of 10.6 % of the target WBL ratio was seen in the group as a whole, although secondary analysis of these results indicated that patients with medial compartment osteoarthritis and/or preoperative mechanical axis of >6 degrees varus accounted for the majority of the cases of undercorrection. LEVEL OF EVIDENCE: Retrospective case series, Level IV. PMID- 25119053 TI - Retention of the posterior cruciate ligament does not affect femoral rotational alignment in TKA using a gap-balance technique. AB - PURPOSE: Previous studies have evaluated the ability of the gap technique to achieve accurate rotational placement in both posterior cruciate ligament (PCL) retaining and PCL-substituting total knee arthroplasty (TKA). The purpose of the present study was to determine (1) the accuracy of this technique in degrees and (2) whether retention of the PCL affects the rotational alignment of the femoral component relative to the transepicondylar axis during TKA. The hypothesis of this study was that retention of the PCL does not affect the femoral rotational alignment in TKA using a gap-balancing technique because both procedures are reported to have good long-term clinical outcomes. METHODS: The femoral rotation angle (FRA) relative to the transepicondylar axis was examined in 206 patients who underwent primary TKA using either PCL-retaining (104 knees) or PCL substituting (102 knees) prostheses to determine the effect of PCL retention on FRA. Quantitative three-dimensional computed tomography was used to assess the FRA in both groups. All values are expressed as median (25th percentile, 75th percentile). RESULTS: Postoperative FRA in the PCL-retaining group was -1.1 degrees (-2.8 degrees , 2.2 degrees ) and in the PCL-substituting group was -0.1 degrees (-2.5 degrees , 2.8 degrees ). The groups were not statistically different. One outlier was found in the PCL-retaining group, and none was found in the PCL-substituting group. CONCLUSIONS: The gap technique reliably allows accurate rotational alignment of the femoral component during TKA despite the retention of the PCL. LEVEL OF EVIDENCE: Therapeutic study, Level II. PMID- 25119054 TI - Comparison of the outcome of early and delayed surgical treatment of complete acromioclavicular joint dislocation. AB - PURPOSE: The aim of this study is to compare the clinical and radiographic results and the complication rate between early and delayed surgical treatment of acromioclavicular joint (ACJ) dislocation. METHODS: Publications in the management of ACJ dislocation are identified from the PubMed database between January 1993 and December 2013 using "acromioclavicular joint" and "dislocation" as keywords. The eligibility criteria included are as follows: (1) ACJ dislocation; (2) intervention, early compared with delayed surgical treatment or the surgical treatment for acute compared with chronic ACJ dislocation; (3) human; and (4) English articles. Exclusion criteria consist of the following: (1) type I and type II ACJ dislocation, (2) no definition of the time of early and delayed surgery in studies, (3) no comparison between the clinical result of early and delayed surgery in studies, (4) laboratory studies, radiographic studies, biomechanical studies, (5) the cases including fractures or revisions in studies, and (6) systematic analyses. RESULTS: Eight studies comparing early and delayed surgical treatment of ACJ dislocation are included in this systematic review. According to Constant scores and shoulder subjective value, early surgery has better functional outcomes than delayed surgery in the treatment of ACJ dislocation (P < 0.05). Partial-dislocation/re-dislocation is found at 26.0 % in early and 38.1 % in delayed surgical treatment (P < 0.05). The rate of CC ossification in early surgical treatment is found as the same as the delayed. The complication rates are found at 12.5 % in early surgical treatment and 17.7 % in the delayed, which is not significantly different. CONCLUSION: Early surgical treatment may have superiority to the delayed procedure in the management of ACJ dislocation with better functional outcomes and more satisfied reduction. However, high-quality evidence studies are required to provide stronger support for this opinion in the future. LEVEL OF EVIDENCE: IV. PMID- 25119055 TI - Radiological outcomes of pinless navigation in total knee arthroplasty: a randomized controlled trial. AB - PURPOSE: This study aimed to investigate the accuracy of pinless navigation (BrainLAB((r)) VectorVision((r)) Knee 2.5 Navigation System) as an intra operative alignment guide in total knee arthroplasty (TKA). The authors hypothesized that pinless navigation would reduce the proportion of outliers in conventional TKA, without a significant increase in the duration of surgery. METHODS: Between 2011 and 2012, 100 patients scheduled for a unilateral primary TKA were randomized into two groups: pinless navigation and conventional surgery. All TKAs were performed with the surgical aim of achieving neutral coronal alignment with a 180 degrees mechanical axis. The primary outcomes of this study were post-operative radiographic assessment of lower limb alignment using hip knee-ankle angle (HKA) and components placement using coronal femoral-component angle (CFA) and coronal tibia-component angle (CTA). RESULTS: There was a smaller proportion of outliers for HKA, CFA and CTA at 10, 2 and 2 % respectively, in the pinless navigation group, compared to 32, 16 and 16 %, respectively, in the conventional group (p = 0.013, p = 0.032 and p = 0.032, respectively). The mean CFA was also more accurate at 90 degrees in the pinless navigation group compared to 91 degrees in the conventional group (p = 0.002). There was no difference in the duration of surgery between the two groups (n.s.). CONCLUSIONS: Pinless navigation improves lower limb alignment and components placement without a significant increase in the duration of surgery. The authors recommend the use of pinless navigation to verify the coronal alignments of conventional cutting blocks in TKA before the bone cuts are made. LEVEL OF EVIDENCE: I. PMID- 25119056 TI - Development of a brief substance use sensation seeking scale: validation and prediction of injection-related behaviors. AB - Sensation seeking, a personality trait, has been shown to predict engagement in high-risk behaviors. However, little is known regarding the impact of sensation seeking on substance use among street youth. We therefore sought to modify a sensation seeking scale (SSS) for use among this population. Street youth from the Vancouver-based At-Risk Youth Study (n = 226) completed the modified SSS. Exploratory and confirmatory factor analysis (EFA/CFA) were undertaken to establish the scale's dimensionality and internal validity. The association between SSS score and injection-related behaviors was tested using generalized estimating equation analysis. EFA results indicated scale unidimensionality. The comparative fit index (CFI) suggested acceptable fit (CFI = 0.914). In multivariate analysis, sensation seeking was independently associated with injection drug use, crystal methamphetamine use, polysubstance use, and binge drug use (all p < 0.05). Our findings provide preliminary support for the use of the modified SSS among street youth. PMID- 25119058 TI - Can the immunological response to botulinum toxin trigger headaches? AB - OnabotulinumtoxinA has recently proved beneficial for the treatment of chronic migraine; even though, headaches are not infrequently reported by patients receiving botulinum toxins for different conditions. Here the author discusses the potential mechanisms on how the immunological response following the application of botulinum toxins may trigger headaches and/or migraine. PMID- 25119060 TI - Kanglaite stimulates anticancer immune responses and inhibits HepG2 cell transplantation-induced tumor growth. AB - Previous studies revealed that Kanglaite (KLT) exhibits antitumor and immunomodulatory activities. In the present study, we show that KLT treatment stimulated the immune response by increasing the number of T cells and natural killer (NK) cells in the blood of hepatocellular carcinoma (HCC) patients. Experiments in tumor-bearing mice were further designed in order to explore the effects of KLT on the immune system and the underlying molecular mechanisms. The results showed that KLT improves the tumor cell transplantation-induced reduction in the serum level of the cytokines IFN-gamma and IL-2, and rescues the levels of CD4+ T cells in host mice. These events enhanced the cytotoxic activities of natural killer and CD8+ T cells against the hepatic HepG2 cancer cells. KLT administration further increased the mRNA level of certain nuclear factor kappaB (NF-kappaB)-responsive genes in CD4+ cells. The chromatin immunoprecipitation assay showed that KLT increases the association of the NF-kappaB p65 subunit to the promoter regions of interleukin (IL)-2- and B-cell lymphoma (Bcl)-2-encoding genes in CD4+ T cells. Our study demonstrated that KLT is the main active ingredient of coix seed exhibiting anticancer and immunomodulatory properties. Induction of NF-kappaB-mediated gene transcription in CD4+ T cells is involved in the immunomodulatory activity of KLT. PMID- 25119059 TI - Novel mechanism of intra-renal angiotensin II-induced sodium/proton exchanger 3 expression by losartan in spontaneously hypertensive rats. AB - The present study aimed to investigate the molecular pharmacodynamic mechanisms of losartan used in the treatment of hypertension. A total of 12 spontaneously hypertensive rats (SHR) were divided randomly into an SHR group treated with saline and LOS group treated with losartan. Six Wistar-kyoto rats (WKY) were enrolled as the WKY group with saline in the study. The LOS group received 30 mg/kg/day losartan by intragastric injection, while the SHR and WKY were fed the same volume of saline. The dosage was modulated according to the weekly weight. Changes in blood pressure were measured by the indirect tail cuff method. Angiotensin (Ang) II production in the plasma and renal tissue was measured by an immunoradiometric method. Na+/H+ exchanger (NHE)3 and serum and glucocorticoid inducible kinase (SGK)1 were assessed by quantitative polymerase chain reaction (qPCR) and western blot analysis. When compared with the WKY group, the blood pressure of the SHR and LOS groups were higher prior to treatment with losartan. Following two weeks, blood pressure was reduced and the trend continued to decrease over the following six weeks. The plasma and renal tissue levels of Ang II in the SHR and LOS groups were significantly higher than those in the WKY group. NHE3 and SGK1 were increased at the mRNA and protein level in the SHR group, and losartan reduced the expression of both of them. The results suggested that in hypertensive rats, the circular and tissue renin angiotensin systems were activated, and the increased Ang II stimulated the expression of NHE3 and SGK1, which was reduced by losartan. Therefore, the effects of losartan in hypertension may be associated with the Ang II-SGK1-NHE3 of intra-renal tissue. PMID- 25119061 TI - The expression of glucagon-like peptide-1 receptor and dipeptidyl peptidase-IV in neuroendocrine neoplasms of the pancreas and gastrointestinal tract. AB - Neuroendocrine neoplasm (NEN) of the pancreas and gastrointestinal tract is infrequent but often produces hormones to cause distinct clinical features. Glucagon-like peptide-1 receptor (GLP1R) is a G-protein coupled receptor for GLP1, which is cleaved by dipeptidyl peptidase (DPP)-IV, a peptidase that regulates the activity of peptide hormones. Since these molecules are involved in the neuroendocrine function of NEN, they could serve molecular targets for diagnosis and therapy of NEN. However, the expressions of these molecules in NEN are not well studied. We therefore examined the expression of GLP1R and DPP-IV in 22 cases of pancreatic NEN (P-NEN) and 20 cases of gastrointestinal NEN (GI-NEN) by immunostaining. GLP1R was expressed in all eight insulinomas (100 %) but so in only four out of 14 cases (29 %) of non-insulinomas. In contrast to GLP1R, DPP-IV was detected in one out of eight insulinomas (13 %) and in 12 out of 14 cases (86 %) of non-insulinomas. In GI-NEN, GLP1R was negative in all 10 cases of the foregut NEN, whereas it was expressed in all three cases (100 %) of midgut NEN and four out of seven cases (57 %) of hindgut NEN. DPP-IV was expressed in five out of 10 cases (50 %) of the foregut NEN. The expression was detected in two out of three cases (67 %) of midgut NEN and in all seven cases (100 %) of hindgut NEN. In conclusion, we found distinct expression patterns of GLP1R and DPP-IV depending on the neuroendocrine cell types in P-NEN and the anatomical sites in GI-NEN. PMID- 25119062 TI - Nintedanib for the treatment of patients with advanced non-small-cell lung cancer. AB - An unmet need remains for effective, well-tolerated treatment options in advanced non-small-cell lung cancer that can alleviate the disease burden for a broad selection of patients. Nintedanib (Vargatef) is a potent, oral, triple angiokinase inhibitor of three distinct pro-angiogenic pathways. A recent Phase III trial of second-line nintedanib plus docetaxel met the primary end point of progression-free survival and demonstrated significant benefit in the key secondary end point of overall survival, with median overall survival greater than 1 year for patients with adenocarcinoma histology. This article summarizes preclinical and clinical experience with nintedanib in non-small-cell lung cancer to date and discusses how it may be used in the future, including prospects for individualizing treatment by tumor proliferation dynamics and molecular biomarkers of response. PMID- 25119063 TI - Effect of iDose4 iterative reconstruction algorithm on image quality and radiation exposure in prospective and retrospective electrocardiographically gated coronary computed tomographic angiography. AB - OBJECTIVES: The aims of this study were to compare a commercially available reconstruction algorithm (iDose4) with filtered back projection (FBP) in terms of image quality (IQ) for both retrospective electrocardiographically gated and prospective electrocardiographically triggered cardiac computed tomographic angiography (CCTA) protocols and to evaluate the achievable radiation dose reduction. METHODS: A total cohort of 58 patients underwent either prospective CTCA or retrospective CTCA with full or reduced tube current-time product (in milliampere-second) protocol on a 64-slice multidetector computed tomographic scanner. All images were reconstructed with FBP, whereas the reduced milliampere second images were also reconstructed using 2 levels (levels 4 and 6) of iDose4. Subjective and objective IQ was evaluated. RESULTS: Dose reductions of 43% in the retrospective CCTA protocol and 27% in the prospective CCTA protocol were achieved without compromising IQ. In the prospective CCTA protocol, the reduced dose images were highly scored; thus, additional reduction of exposure settings is feasible. In the retrospective acquisition, dose reduction has led to similar IQ scores between the reduced-dose iDose4 images and the full-dose FBP images. Considering different reconstructions (FBP, iDose-L4 and -L6) of the same acquisition data, increase in iDose4 level resulted in less noisy images. A slight improvement was also noticed in all IQ indices; however, this improvement was not statistically significant for both acquisition protocols. CONCLUSIONS: This study demonstrated that the application of iDose at CCTA facilitates significant radiation dose reduction by maintaining diagnostic quality. The combination of iDose4 with prospective acquisition is able to significantly reduce effective dose associated with CTCA at values of approximately 2 mSv and even lower. PMID- 25119064 TI - Choosing the best reconstruction technique in abdominal computed tomography: a systematic approach. AB - OBJECTIVE: There is uncertainty regarding the effect of iterative reconstruction (IR) techniques and other reconstruction algorithms on image quality. The aim of this study was to optimize image quality in relation to radiation dose in computed tomography (CT) liver examinations by comparing images reconstructed with different abdominal filters with and without IR. METHODS: An anthropomorphic phantom was scanned on a Toshiba Aquilion ONE CT scanner. Images at 2 different dose levels were reconstructed with 12 different body reconstruction filters, all with both filtered back-projection and Adaptive Iterative Dose Reduction 3 dimensional. Receiver operating characteristic curves were constructed. The 2 reconstruction combinations with the highest scores from the phantom study were evaluated in a second comparison of clinical images. Six liver examinations were reconstructed with both filters and evaluated using visual grading analysis. RESULTS: Two combinations of reconstruction filters and IR were the only 2 options among the 8 best images at both dose levels (area under the curve, 0.96 and 0.94 for 15 mGy as well as 0.86 and 0.84 for 10 mGy). In the patient study, one of these filters in combination with IR scored slightly higher than the other in combination with IR (mean score, 2.60 and 2.57, respectively; P = 0.56). Iterative reconstruction did not significantly increase lesion detectability for any of the filters. CONCLUSIONS: This study indicates that the preferred choice for reconstruction of CT liver examinations performed with the Toshiba Aquilion ONE should be the FC18 filter with IR, although the IR technique did not significantly improve lesion detectability and did not compensate for the dose reduction in this study. PMID- 25119065 TI - Computed tomography imaging manifestations of commonly used materials in posttraumatic craniofacial repair. AB - An expansive array of materials exists within the armamentarium of craniofacial surgeons. For patients undergoing repair of posttraumatic injuries, computed tomography is the imaging modality of choice in the postoperative setting. Therefore, radiologists will invariably encounter implants constructed with various materials, depending on the surgeon's preference. The appearance of these materials on computed tomography is broad, ranging from hyperdense to radiolucent. To avoid misdiagnosis, radiologists should be familiar with all of the materials currently in use. PMID- 25119066 TI - Perceptions of users and providers on barriers to utilizing skilled birth care in mid- and far-western Nepal: a qualitative study. AB - BACKGROUND: Although skilled birth care contributes significantly to the prevention of maternal and newborn morbidity and mortality, utilization of such care is poor in mid- and far-western Nepal. This study explored the perceptions of service users and providers regarding barriers to skilled birth care. DESIGN: We conducted 24 focus group discussions, 12 each with service users and service providers from different health institutions in mid- and far-western Nepal. All discussions examined the perceptions and experiences of service users and providers regarding barriers to skilled birth care and explored possible solutions to overcoming such barriers. RESULTS: Our results determined that major barriers to skilled birth care include inadequate knowledge of the importance of services offered by skilled birth attendants (SBAs), distance to health facilities, unavailability of transport services, and poor availability of SBAs. Other barriers included poor infrastructure, meager services, inadequate information about services/facilities, cultural practices and beliefs, and low prioritization of birth care. Moreover, the tradition of isolating women during and after childbirth decreased the likelihood that women would utilize delivery care services at health facilities. CONCLUSIONS: Service users and providers perceived inadequate availability and accessibility of skilled birth care in remote areas of Nepal, and overall utilization of these services was poor. Therefore, training and recruiting locally available health workers, helping community groups establish transport mechanisms, upgrading physical facilities and services at health institutions, and increasing community awareness of the importance of skilled birth care will help bridge these gaps. PMID- 25119069 TI - Coping with the longevity revolution. PMID- 25119067 TI - A novel Interactive Health Communication Application (IHCA) for parents of children with long-term conditions: Development, implementation and feasibility assessment. AB - BACKGROUND: Few evidence-based, on-line resources exist to support home-based care of childhood long-term conditions. METHODS: In a feasibility study, children with stages 3, 4, or 5 chronic kidney disease, parents and professionals collaboratively developed a novel Online Parent Information and Support (OPIS) application. Parents were randomized to an intervention arm with access to OPIS or a control arm without access. OPIS usage was assessed using Google Analytics. Parents in the intervention arm completed the Suitability Assessment of Materials (SAM) and User Interface Satisfaction (USE) questionnaires and participated in qualitative interviews. RESULTS: Twenty parents accessed OPIS with a mean of 23.3 (SD 20.8, range 2-64) visits per user. Responses from the SAM and USE questionnaires were positive, most respondents rating OPIS highly and finding it easy to use. Qualitative suggestions include refinement of OPIS components, enabling personalization of OPIS functionalities and proactive endorsements of OPIS by professionals. CONCLUSIONS: Implementation of OPIS into standard practice is feasible in the centre where it was developed. Suggested developments will augment reported strengths to inform ongoing testing in the wider UK network of units. Our design and methods are transferrable to developing and evaluating web applications to support home-based clinical care-giving for other long-term conditions. PMID- 25119070 TI - [Significances of the life experience for the long-lived elderly person in the process of death/dying and mourning]. AB - This is a study using the Heideggerian theoretical-phenomenological approach, which sought to understand the significances of the life experience for the long lived elderly person in the process of death/dying and mourning. It was conducted in 2009 with 16 long-lived senior citizens of both genders who were aged between 80 and 90, members of a community center for the elderly located in a suburban neighborhood of the city of Salvador in the state of Bahia, Brazil. The results showed that the long-lived elderly person experiences the mourning status process when relatives and friends become ill and die. Furthermore, they gave ambiguous reports with respect to the fear of death. With the attributed significances, it was possible to arrive at the unit of significance, namely the authenticity and lack of authenticity of the individual regarding imminent death. The conclusion reached is that long-lived elderly individuals faced with the process of death/dying and mourning is apparent or concealed in accordance with the moment they are experiencing and the opportunities that present themselves, in other words, it is greatly influenced by their past. PMID- 25119068 TI - Attention-deficit/hyperactivity disorder and risk for drug use disorder: a population-based follow-up and co-relative study. AB - BACKGROUND: Although the association between attention-deficit/hyperactivity disorder (ADHD) and drug use disorder (DUD) is well documented, it is unclear whether it is causal or results from familial confounding. METHOD: In this study we included all 551 164 individuals born in Sweden between 1991 and 1995 and used linked data from multiple nationwide registries to identify those with ADHD prior to age 15 years (1.71%). We used Cox proportional hazards models to investigate the future risk for DUD as a function of an ADHD registration and then compared the results from the entire population with the results from a co-relative design. Using the Swedish Multi-Generation Register, we identified all full sibling, half-sibling and first-cousin pairs discordant for ADHD. RESULTS: In the population sample, ADHD had a substantially increased risk for future DUD with a hazard ratio (HR) of 3.34 after accounting for gender and parental education. Examining discordant cousin pairs, discordant half-siblings and discordant siblings, those with ADHD had HRs for DUD of 3.09, 2.10 and 2.38 respectively. Controlling for the number of ADHD registrations, ADHD patients with and without stimulant treatment were similarly associated with later DUD risk. CONCLUSIONS: ADHD diagnosed before 15 years of age was strongly related to future risk for DUD. The magnitude of this association was modestly reduced in relative pairs discordant for ADHD, suggesting that the ADHD-DUD association is partly causal and partly a result of familial confounding. We found no evidence to suggest that this association resulted from stimulant treatment. PMID- 25119057 TI - Mutational consequences of aberrant ion channels in neurological disorders. AB - Neurological channelopathies are attributed to aberrant ion channels affecting CNS, PNS, cardiac, and skeletal muscles. To maintain the homeostasis of excitable tissues, functional ion channels are necessary to rely electrical signals, whereas any malfunctioning serves as an intrinsic factor to develop neurological channelopathies. Molecular basis of these disease is studied based on genetic and biophysical approaches, e.g., loci positional cloning, whereas pathogenesis and bio-behavioral analysis revealed the dependency on genetic mutations and inter current triggering factors. Although electrophysiological studies revealed the possible mechanisms of diseases, analytical study of ion channels remained unsettled and therefore underlying mechanism in channelopathies is necessary for better clinical application. Herein, we demonstrated (i) structural and functional role of various ion channels (Na(+), K(+), Ca(2+),Cl(-)), (ii) pathophysiology involved in the onset of their associated channelopathies, and (iii) comparative sequence and phylogenetic analysis of diversified sodium, potassium, calcium, and chloride ion channel subtypes. PMID- 25119071 TI - [Evaluation of the functional capacity of the elderly and factors associated with disability]. AB - The scope of this study was to evaluate the functional capacity and analyze the characteristics associated with the disability of elderly individuals attended in a Family Health Strategy Unit in Montes Claros in the state of Minas Gerais. The Lawton and Brody scale and the Katz scale were used and then analyzed using multinomial logistic regression. 286 elderly individuals were interviewed with ages ranging from 60 to 103 years and a mean age of 71.2 years (SD +/- 8.3). Of these, 61.9% self-reported their independence in terms of functional capacity. The dependence only in IADL was positively associated with age >= 75 years (OR = 8.38), female gender (OR = 3.64) and heart disease (OR = 3.24). The dependence in IADL and ADL was positively associated with age >= 75 years (OR = 6.40), without a partner (OR = 3.26), those who had had a stroke (OR = 51.85), heart disease (OR = 4.18) and diabetes (OR = 3.35). The highest proportion of elderly was considered independent to carry out basic and instrumental activities of daily living. However, a significant portion still has impaired functional status. It is essential that the teams of the Family Health Strategy strive for health promotion and disease prevention, and therapeutic interventions that can minimize the factors that influence functional capacity. PMID- 25119072 TI - Effect of the elimination of chronic diseases on disability-free life expectancy among elderly individuals in Sao Paulo, Brazil, 2010. AB - The scope of this study was to establish whether the elimination of certain chronic diseases is capable of leading to the compression of morbidity among elderly individuals in Sao Paulo (Brazil), 2010. A population-based, cross sectional study was carried out with official data for the city of Sao Paulo (Brazil) in 2010 and data from the SABE (Health, Wellbeing and Ageing) study. A total of 907 elderly individuals were evaluated, 640 of whom were women (64.6%). Sullivan's method was used for the calculation of disability-free life expectancy (DFLE). Life tables for cause elimination were used to calculate the probabilities of death with the elimination of health conditions. In absolute terms, the gains in LE and DFLE were greater in the younger age group (60 to 74 years) in both genders. In relative terms (%DFLE in LE), the gains were higher among women aged 75 years or older and among men aged 60 years. If eliminated, heart disease was the condition that would most lead to the compression of morbidity in both genders. The elimination of chronic diseases from the elderly population could lead to a compression of morbidity in men and women at both 60 years of age and 75 years of age or older. PMID- 25119073 TI - [Influence of voice and hearing changes in the quality of life of active elderly individuals]. AB - This article seeks to verify the self-rated impact of voice and hearing changes of active elderly individuals in their daily lives, and the influence of this self-rating on quality of life. A cross-sectional study was conducted with 72 elderly individuals of an Open University for Senior Citizens in the state of Sao Paulo. The questionnaires applied were HHIE-S; VHI and WHOQoL-Old. The Pearson correlation coefficient was used adopting a p-level significance value of < 0.05. The impact of hearing difficulties on daily life was perceived by 45.8%, and moderate or severe voice handicap by 9.7% of the elderly individuals. The self rating of hearing impact on daily life was correlated with the voice handicap index. Quality of life was negatively affected by the increase in self-rating of hearing and voice difficulties in daily life. The sample profile is typical of successful aging with the acceptance of aging changes and consequently less impact on daily lives than expected. The findings suggest that there is an impact of voice and hearing handicap on quality of life, although it has revealed high indices, bolstering the characteristic of adaptation of the sample to aging. The results justify the need for improving actions of self-care and empowerment for the elderly. PMID- 25119074 TI - [Gait speed, grip strength and self-rated health among the elderly: data from the FIBRA Campinas network, Sao Paulo, Brazil]. AB - The article seeks to investigate patterns of performance and relationships between grip strength, gait speed and self-rated health, and investigate the relationships between them, considering the variables of gender, age and family income. This was conducted in a probabilistic sample of community-dwelling elderly aged 65 and over, members of a population study on frailty. A total of 689 elderly people without cognitive deficit suggestive of dementia underwent tests of gait speed and grip strength. Comparisons between groups were based on low, medium and high speed and strength. Self-related health was assessed using a 5-point scale. The males and the younger elderly individuals scored significantly higher on grip strength and gait speed than the female and oldest did; the richest scored higher than the poorest on grip strength and gait speed; females and men aged over 80 had weaker grip strength and lower gait speed; slow gait speed and low income arose as risk factors for a worse health evaluation. Lower muscular strength affects the self-rated assessment of health because it results in a reduction in functional capacity, especially in the presence of poverty and a lack of compensatory factors. PMID- 25119075 TI - [Drug prescriptions of patients treated in a geriatric outpatient ward of a university hospital: a descriptive cross-sectional study]. AB - The scope of this study was to evaluate drug prescriptions for elderly patients in the geriatric outpatient ward of a hospital. A cross-sectional descriptive study was conducted in a university hospital, with the application of a questionnaire. Patients aged >60 years were interviewed about their drug prescriptions and a total of 208 patients were interviewed. The average number of drugs used per person was 3.8 and the drugs most used were for the cardiovascular system (37%). 406 potential interactions were identified in 140 patients (67.3%), and duplicate therapy was found in two prescriptions. The potentially inappropriate drug most used for the elderly was nifedipine (2.4%). Data from this study support the relevance of the issue of drug use among the elderly, thus reinforcing the importance of the evaluation of the process of the prescription of drugs for this population. PMID- 25119076 TI - [Vestibular rehabilitation in the quality of life and the symptomatology of dizziness among the elderly]. AB - The scope of this paper was to analyze the effect of a structured protocol of vestibular rehabilitation in the symptomatology of dizziness and the quality of life among the elderly. Nine elderly individuals were attended, namely four males and five females. The Dizziness Handicap Inventory (DHI) was used to assess quality of life and the dizziness quantification scale for the symptomatology of dizziness. A protocol for vestibular rehabilitation consisting of group activities was then developed. The Wilcoxon test and Student t-test were used for data analysis. The Spearman correlation coefficient was used to analyze the relationship between quality of life and the symptomology of dizziness. The significance level used was 5%. There was significant improvement in the symptomatology of dizziness, overall quality of life and physical, emotional and functional aspects after completion of the program. There was also a good positive correlation between the symptomatology of dizziness and quality of life. The conclusion reached was that program participants had a significant improvement of dizziness, general quality of life and their respective vestibular rehabilitation aspects. There was also a good correlation between symptomatology of dizziness and overall quality of life. PMID- 25119077 TI - [Ways of thinking and acting of the elderly when tackling functionality/disability issues]. AB - Functionality is a crucial dimension of the health of the elderly. The aim of this work is to investigate the elements that comprise the significance of disability for the elderly residents of the city of Bambui in the state of Minas Gerais. A qualitative approach was adopted in which the model of signs, significance and actions was used in both data collection and analysis. Interviews were conducted with 57 elderly individuals (30 women; 27 men) ranging from 61 to 96 years of age registered in primary care units. The participants interpret functionality/disability (disease) as "being able to cope/not being able to cope" or "being a burden" (illness) to others. "Not being able to cope" refers to the inexorable functional loss inherent to the aging process, while "being a burden" relates to the permanent condition of generating pain and suffering to both patient and care giver. The way to deal with the "not being able to cope" condition is related to resignation. On the other hand, praying is the way to deal with "being a burden." Religion and resignation can help during critical moments, though they also reveal the lack of resources and alternatives for support and intervention in the most severe cases. PMID- 25119078 TI - [Seroepidemiology of Toxoplasma gondii in elderly individuals treated under the Family Health Strategy, Porto Alegre, Rio Grande do Sul, Brazil]. AB - The aim of this study was to evaluate the seroprevalence of Toxoplasma gondii and relate it to the socioeconomic, hygienic, sanitary and health conditions of the elderly of the Family Health Strategy (FHS) in the city of Porto Alegre, Rio Grande do Sul, Brazil. The research involved a cross-sectional study in which a questionnaire with epidemiologic questions was applied and blood samples were taken. The assessment of IgG and IgM anti-T. gondii was performed using the ELISA technique. Seroprevalence was evaluated among 599 elderly individuals with 88% for IgG anti-T. gondii and with 0.8% for IgM. In the multivariate analysis, the variables that associated themselves independently with positive IgG were age range, personal income and wearing spectacles. Those associated with positive IgM were age, self-rated health and wearing spectacles. The results call attention to the high prevalence of IgG anti-T. gondii in elderly individuals in the FHS in Porto Alegre, generating concern in the event that the reactivation of toxoplasmosis and the development of more severe symptoms of this infection occur. PMID- 25119079 TI - [Cost and characterization of hospital infection among the elderly]. AB - The increase in the number of elderly individuals has a direct impact on the health system with hospitalization complications such as hospital infection (HI). The objective of this study is to characterize and evaluate the cost of HI among the elderly in a public hospital for the elderly. Descriptive, cross-sectional research was conducted. Elderly individuals with HI in 2010 comprised the population of the study. The data were drawn from hospital records and analysis was performed using Excel 2003 and SPSS software. The results indicated that 341 seniors participated in the study with a HI index 3% higher than the monthly average. The most frequent infectious sites were: respiratory tract infection (58.1%), urinary tract infection (28.6%) and surgical infection (4.6%). Each hospitalization cost R$ 28,714.10 on average and 5% of this amount was for antibiotics. The increase of 15 days average added R$ 17,946.3 to costs of hospitalization. The conclusion drawn is that the elderly have increased vulnerability to HI. The infections extend the hospitalization period and increase costs varying according to the nature of the infection. PMID- 25119080 TI - [Primary healthcare geared to the needs of the elderly: from theory to practice]. AB - This article seeks to establish a confrontation between theory and practice with respect to healthcare for the elderly. The theory was evaluated by a study of documents that comprise the legal and theoretical framework related to the health of the elderly, which generated a matrix to assess universal access, equity, comprehensiveness and quality of care. However, the practice of healthcare was evaluated by a population-based study conducted on 862 elderly individuals and a census that assessed primary healthcare (PHC) units in two districts of Porto Alegre in the state of Rio Grande do Sul, Brazil. The variables chosen to verify the categories were type of care accessed, first contact attribute, wheelchair accessibility and availability of priority access. Other variables include comprehensive care and the presence of dental root remains, basic PHC score, the adequacy of health facilities and ongoing professional training, as well as cross sectional categories, elderly groups and home care. A mismatch was found between recommendation and practice in some factors and advances were observed in the equity and quality of care regarding the ongoing training of professionals. PMID- 25119081 TI - [Do elderly individuals with a cognitive handicap have worse oral health?]. AB - A comparison of the oral health of elderly people with and without a cognitive handicap was assessed. The cognitive condition, the indices of decayed, missing, filled teeth (DMFT), decayed, filled roots (DFR), the need for dental treatment, the presence of plaque (P), calculus (C), the community periodontal index (CPI), the rate of periodontal attachment loss (PAL), edentulism, prosthetic use and the need for prosthetics were evaluated in a complex probabilistic sample by conglomerates of the elderly (65-74 years). PASW(r) 17.0 was used for the statistical analyses with correction for the design effect, applying the Mann Whitney and chi-square test with 95% reliability. A total of 736 elderly individuals were interviewed and examined. Those with cognitive impairment had higher average DMFT, DFR and lower average healthy sextant CPI, a lower prevalence of sextants without plaque/calculus, use of prosthetics and higher prevalence of edentulism and need for prosthetics. Elderly individuals with a cognitive handicap had poorer oral health. PMID- 25119082 TI - [Factors associated with satisfaction with life among elderly caregivers and non caregivers]. AB - This article seeks to investigate associations between satisfaction with life and sociodemographic variables, health conditions, functionality, social involvement and social support among elderly caregivers and non-caregivers, as well as between satisfaction and the intensity of stress in the caregiver group. A sample of 338 caregivers was selected according to two items of the Brazilian version of the Elders Life Stress Inventory. A comparison-group of elderly non-caregivers was selected at random, with a similar gender, age and income profile. Data were derived from self-reported questionnaires and scales. Elderly caregivers with low levels of satisfaction and high levels of stress revealed more symptoms of insomnia, fatigue, diseases and worse IADL performance. Those with greater satisfaction and less stress revealed a good level of social support. Insomnia, depression and fatigue were associated with low satisfaction among caregivers, and with fatigue, depression and low social support among non-caregivers. It was considered relevant that instrumental, psychological and informative support can improve the quality of life and the quality of care provided by elderly caregivers, especially if they are affected by unfavorable health and psychosocial conditions and low satisfaction with life. PMID- 25119083 TI - [Assessment of the technology of care relations in the health services: perception of the elderly included in the family health strategy in Bambui, Brazil]. AB - In the health field, technologies of care relations are in the scope of the worker-user encounter, implying intersubjectivity with the development of relationships between subjects, resulting in action. Evaluation studies synthesize knowledge produced on the consequences of using these technologies for society. This anthropological study aims to understand the perception of the elderly regarding the resolution capability and effectiveness of the acts produced in health care relationships in the context of the Family Health Strategy (ESF). The group studied consisted of 57 elderly residents in Bambui, State of Minas Gerais, Brazil. The model of signs, meanings and actions was used for collecting and analyzing data and the semi-structured interview was applied as a research technique. Elderly individuals assess resolution capability and effectiveness of the acts of care in the ESF as negative, with relation to the quality of user and professional interaction. The ESF is not effective and the desired change in the health care model has not occurred in practice. It repeats the centrality of the medical-drug-procedure model that treats the disease rather than the patient, perceiving old age as a disease and illness as being related to aging. PMID- 25119084 TI - [Body image perception and associated factors among elderly residents in a city in northeast Brazil: a population-based study]. AB - The article aims to verify body image perception and associated factors among elderly individuals in Campina Grande, State of Paraiba. It involves a cross sectional, population and home-based study, with individuals 60 years or older of both sexes. Body image perception was considered the dependent variable for purposes of analysis and study of possible associations. The independent variables were: age group, nutritional status, number of diseases, health perception and regular practice of physical activities. To identify associated factors, univariate and multivariate regression analyses were carried out using SPSS 17.0 software. Overall, 806 elderly individuals were interviewed. Men showed greater satisfaction with body image when compared to women and older participants were more satisfied than younger participants. Among the factors related to dissatisfaction in women, underweight and overweight/obesity were associated with an increased risk of dissatisfaction. Among men, older age constituted a protective factor for dissatisfaction, while underweight and overweight/obesity were risk factors for dissatisfaction. The results of this study suggest a possible influence of nutritional status on body image perception among the elderly, negatively affecting their perception of body image. PMID- 25119085 TI - [Association between physical and psychosocial impacts of oral disorders and quality of life among the elderly]. AB - This study sought to evaluate the association between the impact of oral disorders in terms of physical/psychosocial dimensions and quality of life among the elderly. It involved a cross-sectional study conducted among the elderly (65 74 years) in 2008/2009. The social impact was assessed using the Oral Health Impact Profile (OHIP 14) and the quality of life using the SF 12 Short-Form Health Survey. Descriptive, univariate and multivariate (logistic regression) analysis was conducted with correction for the design effect, using SPSS(r)18.0 software. Of the 800 individuals approached, 736 elderly individuals participated (TR = 92%), with a mean age of 67.77 years, the majority of whom showed no impact based on the measurement of the prevalence of OHIP. The functional limitation dimension of the OHIP was associated with the physical domain of the SF12, irrespective of the other variables investigated. However, the seriousness of OHIP and its psychological discomfort and disability dimensions was associated with the mental domain of the SF12. The conclusion reached is that some impacts of oral disorders were associated with unsatisfactory quality of life in the physical and mental domains. PMID- 25119086 TI - [Male participation in types of physical activities of a program for the elderly: a longitudinal study]. AB - The article seeks to describe male participation on a physical activity program for the elderly in the south of Brazil over a ten-year period (2003-2013). The data of the study were extracted from a database and assessed using descriptive and inferential statistics and assessment of the thematic content. The first phase of the study was longitudinal (from 2003 to 2013) with 163 elderly participants, while the second phase was cross-sectional for the year of 2013 with 45 elderly individuals. Male participation was, on average, 3.5 times lower than female participation for all years assessed, and the activity most practiced was swimming. In the year 2013, the average age of the elderly men was 68 +/- 7.8 years. Most of them are married, have tertiary education, good acquisitive power, positive self perception of health, one or more diagnosed diseases, and do not participate in any other physical activity outside the program. According to the elderly, the reasons for participating most cited was the search for quality of life and health and, for continuing to exercise, acquiring the taste for the physical activity. Understanding the profile of these individuals and of the reasons that motivate them are important tools to comprehend the issue and help to define public politics directed at this population group. PMID- 25119087 TI - [Physical inactivity among non-institutionalized elderly individuals: a population-based study]. AB - The scope of this study is to assess the prevalence of physical inactivity among the elderly in Northeast Brazil and analyze the associated lifestyle and socio demographic factors and health conditions. The work presented here is a descriptive and association-based study using secondary data derived from a population-based epidemiological study that included 316 elderly participants. The physical activity level of each participant was assessed using the International Physical Activity Questionnaire. The explanatory variables examined in this study were gender, age group, family set-up, ability to read and write, paid or voluntary employment, smoking, symptoms of depression, high blood pressure, fasting hyperglycemia and functional capacity. The prevalence of physical inactivity was 46.5. The results of the multivariate analysis indicated that physical inactivity was positively associated with the age group >= 80 years (PR = 2.37), with the lack of an occupation (PR = 4.86) and with dependence on instrumental activities of daily life (PR = 1.47) and basic activities of daily life (PR = 1.60). Physical inactivity was highly prevalent in the surveyed population, making it essential to discuss programs that encourage and enable increased physical activity to combat the risk factors of a sedentary lifestyle. PMID- 25119088 TI - [Influence of socioeconomic factors on the quality of life of elderly hypertensive individuals]. AB - This study sought to evaluate the association between socioeconomic variables and the quality of life of elderly hypertensive patients treated under the Family Health Program in the city of Montes Claros, Minas Gerais, Brazil. An analytical cross study was conducted in a representative sample of 294 elderly hypertensive patients. Data were collected using a questionnaire on socioeconomic characteristics and quality of life (MINICHAL). The data were analyzed using the nonparametric Mann-Whitney and Kuskall-Wallis tests. The results showed that marital status, religion and education affect the quality of life of elderly hypertensive patients in a statistically significant way. Elderly hypertensive patients who were single/divorced/widowed, evangelical, spiritualist and belonging to other religious bodies, illiterate achieved lower scores in terms of quality of life. For the remaining variables, there was no statistical association. The conclusion, drawn is that socioeconomic factors such as marital status, education and religion influence the quality of life of elderly hypertensive patients. PMID- 25119089 TI - [Factors related to the quality of life of the elderly in programs for senior citizens]. AB - Population aging is a social phenomenon that demands the attention of health professionals. This article seeks to analyze the influence of possible intervening factors on the quality of life of the elderly. It was a cross sectional, quantitative, descriptive and exploratory study, in which 182 elderly of both genders participated. They were aged >= 60 years and were enrolled in programs for senior citizens from three universities located in the cities of Sao Paulo, Sao Caetano do Sul and Mogi das Cruzes. To evaluate the subjective perception of quality of life, the World Health Organization Quality of Life questionnaire (WHOQOL-Bref) was used. Multiple linear regression analysis was performed on the dependent and independent variables. A significance level of 5% was adopted. The results showed that the absence of disease positively influenced the quality of life on the four domains evaluated. In the environmental domain, full tertiary education, old age, the absence of disease and being a resident in Sao Caetano do Sul positively influenced the quality of life of the elderly. The factors associated with better quality of life were: full tertiary education, old age, the absence of disease and being a resident in Sao Caetano do Sul, in that order of importance. PMID- 25119090 TI - [Low weight and functional disability in institutionalized elderly interns in Uberlandia in the State of Minas Gerais, Brazil]. AB - This article seeks to identify the association between nutritional status and functional dependence in institutionalized elderly interns in Uberlandia, Minas Gerais. It involved a cross-sectional study with 233 elderly interns in which sociodemographic variables, nutritional status and degree of dependency were assessed. Multivariate analysis was performed using Poisson regression with robust variance to assess the association between nutritional status and functional dependence of these senior citizens. Low weight by the Body Mass Index was associated with functional dependence after controlling for socioeconomic and demographic variables. The elderly with low weight had a prevalence ratio of dependence of 1.2 times the prevalence rate of dependence of well nourished elderly interns. As reported in the literature, age was also associated with dependence with a prevalence ratio of 1.19 for the longest living. Low weight is an important factor associated with functional disability. Thus, the need for evaluation, monitoring and recovery of nutritional status in the institutionalized elderly is stressed, as in addition to reducing morbidity and mortality from several diseases and improve quality of life, it can also prevent and delay functional dependency. PMID- 25119092 TI - [Factors that influence the sexuality of the elderly: an integrative review]. AB - The scope of this article is to analyze the scientific evidence addressing the factors that influence the sexuality of the elderly. It involved an online search carried out in pairs, including original articles published between 2006 and October 2011 in Portuguese, English or Spanish, which fulfilled the requirements of the study. The MEDLINE, LILACS, CidSaude and BDENF databases were used with the key words: sexualidade e idoso / sexuality and elderly / sexualidad y anciano. The articles selected were assessed for methodological quality using two instruments, namely CASP and the Hierarchical Classification of Evidence. After analysis, 15 articles were included in the review, which discuss the culture of asexuality of the elderly, whereby the experience of sexuality only prevails among younger people. The absence of the partner due to widowhood, attributing value to beauty standards of the young, the occurrence of disease, use of medication, and changes in sexual physiology were identified as important factors that influence the sexuality of the elderly. The conclusion drawn is that social and cultural factors, changes in body physiology, and the occurrence of disease interfere with the sexuality of the elderly, making it necessary for nursing professionals to be proactive in debunking myths and providing orientation. PMID- 25119091 TI - [Evaluation of the quality of primary health care from the perspective of the elderly]. AB - The scope of this study was to assess the quality of Primary Health Care (PHC) provided to the elderly from their viewpoint. The study design was cross sectional and observational in a stratified random sample of elderly individuals, enrolled in 10 of the 20 Basic Health Units (BHU) in the city of Macaiba, State of Rio Grande do Norte, Brazil. After an interview conducted using the adult version of the primary care assessment tool (PCATool-Brazil), the quality level was estimated (0-10, based on desirable attributes) and the association between demographic and socioeconomic factors was analyzed. The participants (n = 100) assigned a score of fair (5.7) to Quality; Longitudinality of care was awarded a high score (7.3), however Integrality (4.7), Family Orientation (4.1) and Accessibility (3.8) were considered weak. Socio-demographic factors linked to vulnerability (low income, rural area and older age) were positively associated with different PHC attributes. A margin for improvement in PHC attributes was observed, especially with respect to increasing the focus on the family, extending working hours in BHUs and enhancing prevention of diseases and ensuing complications. PMID- 25119093 TI - [Factors associated with the danger of accidental falls among institutionalized elderly individuals: an integrative review]. AB - The scope of this research is to identify the major risk factors associated with accidental falls among the elderly. It involves an integrative review of the literature between 2002 and 2012 in English and Portuguese. The selection of articles was based on the following key words in the Lilacs, Medline and BDENF databases: accidental falls, homes for the elderly and health services. In the final sample 19 articles were selected, of which 11 were national and 8 were international. They indicate that the major factors related to the risk of accidental falls in Homes for the Elderly are: being female, being diagnosed with chronic disease, treatment with benzodiazepine, earlier cases of accident falls, and mobility restriction. The research reveals that architectonic and furniture inadequacies in Homes for the Elderly may be predisposing factors for accidental falls. Analysis of the articles reveals the need for further longitudinal studies and, consequently, enhanced monitoring of the conditions of the functional capacity of the elderly, especially the risks related to falls, considered one of the leading causes of death among institutionalized elderly individuals. PMID- 25119094 TI - [Health promotion in primary care: study based on the Paulo Freire method]. AB - The scope of this study is to analyze the implementation of health promotion actions in the working process of the Family Health Teams of a city in the state of Santa Catarina. It involves research adopting a qualitative approach linked to the methodological benchmark of Paulo Freire, consisting of three dialectic moments: thematic investigation; encoding and decoding; critical revelation. Fifteen Culture Circles were conducted, covering five district health units, with the participation of 70 professionals. Each meeting was scheduled to last two hours with an average attendance of thirteen participants of the Family Health teams. The research revealed that there are limitations to the implementation of health promotion as a key element of participatory action together with the community. It also highlighted the importance of interdisciplinarity and intersectorality between workers and the city, state and federal manager. The commitment to the principles of the Unified Health System (SUS) and health promotion also presents itself as a challenge to improve the quality of life of the population. PMID- 25119095 TI - [The Singular Therapeutic Project and mental health practices at Family Health Support Centers in Guarulhos in the state of Sao Paulo, Brazil]. AB - Various studies describe the Singular Therapeutic Project (STP) as a powerful instrument of care for the users of specialized mental health services. It is also put forward as a tool to organize and support the activities of the Family Health Support Centers (FHSC), based on the concepts of co-responsibility and comprehensive care. The article seeks to analyze the development of STP by mental health teams of FHSC and its articulations with services of Primary Health Care (PHC), psychosocial services and other sectors of society. It involved qualitative research performed in Guarulhos in the state of Sao Paulo in 2012 by systematic observation and conducting semi-structured interviews with mental health professionals from support centers. The content analysis method was employed for interpretation of the findings. The STP in FHSC faces obstacles related to lack of definition of work object (attention or management?), precarious working conditions and overlapping functions. It is necessary to analyze the technological feasibility of the STP based on the peculiarities of PHC, avoiding straightforward transposition of technological tools among the different services that comprise the psychosocial care network. PMID- 25119096 TI - [Cross-cultural adaptation and validation of the Health and Taste Attitude Scale (HTAS) in Portuguese]. AB - The scope of this study was to show the cross-cultural adaptation and validation of the Health and Taste Attitude Scale in Portuguese. The methodology included translation of the scale; evaluation of conceptual, operational and item-based equivalence by 14 experts and 51 female undergraduates; semantic equivalence and measurement assessment by 12 bilingual women by the paired t-test, the Pearson correlation coefficient and the coefficient intraclass correlation; internal consistency and test-retest reliability by Cronbach's alpha and intraclass correlation coefficient, respectively, after application on 216 female undergraduates; assessment of discriminant and concurrent validity via the t-test and Spearman's correlation coefficient, respectively, in addition to Confirmatory Factor and Exploratory Factor Analysis. The scale was considered adequate and easily understood by the experts and university students and presented good internal consistency and reliability (u 0.86, ICC 0.84). The results show that the scale is valid and can be used in studies with women to better understand attitudes related to taste. PMID- 25119097 TI - [Meat consumption by adults in southern Brazil: a population-based study]. AB - This paper is the result of a cross-sectional population-based study that evaluated individuals aged 20 or more living in the urban area of Pelotas in the state of Rio Grande do Sul and sought to describe the frequency of meat consumption and the habit of eating meat with an excess of fat. It evaluated the consumption over the past year of red meat (including bone, steak and ground beef), white meats (chicken and fish) and viscera and processed meats. Of the 2,730 people interviewed, 99.1% (CI95% 98.7 - 99.5) consumed some type of meat over the past year, while around 32% reported daily consumption. The prevalence of consumption of red meat (99.3% CI95% 98.9 - 99.6) and white meat (99.4% CI95% 99.1 - 99.7) was similar. Chicken was the meat most consumed by interviewees (98.0% CI95% 97.4 - 98.5), while viscera were the least consumed (59.1% CI95% 56.4 - 61.7). The processed meats consumed by 85.5% (CI95% 83.7 - 87.2) of the respondents, presented the highest prevalence of daily consumption (16.6%). Meats with excess of fat were consumed by 52.3% (CI95% 49.8 - 54.8) of adults, especially men and people of lower education and economic status. PMID- 25119098 TI - [Contractual arrangements in primary health care: the experience of Portugal and Brazil]. AB - The contractual arrangements adopted in the Family Health Strategy are a topic as yet scantly addressed in studies. It is introduced in Brazil in different models in accordance with the contracting entity and the legal status of the contracted service provider; and in Portugal, it is based on a model of inter-governmental contractual arrangements with the Family Health Units. In this paper, the current status of contractual arrangements in both countries is presented and their attributes of joint planning, accountability with autonomy and performance-based incentive programs are discussed. The main contributions are: better coordination of the health organizations; substitution of the hierarchical command-control logic with greater participation; and accountability of professionals with enhanced performance of their activities. The conclusion reached is that one of the facilitating elements is gradual construction, in an environment of ongoing learning, with health professionals playing the leading role. However, the major challenges include transparency in the implementation of processes, the enforcement of sound auditing mechanisms and information systems, as well as the continuous review of indicators and their suitability for the health needs of the population. PMID- 25119099 TI - [Alteration of profile of treatment of the public psychiatric hospitals of Belo Horizonte, Brazil, in the context of mental health care reform]. AB - This article seeks to describe the profile of treatment and internment in public psychiatric hospitals in Belo Horizonte, Brazil, from 2002 to 2011. The changes in the characteristics of treatment and the profiles of the patients treated are analyzed in the context of health care reform. It is a study of temporal series with trend analysis by means of linear regression. There was a reduction in the total of patients treated in the period under scrutiny. Inversely, there was an increase in internments with a reduction in length of stay, though no change in readmission rates. Patients from Belo Horizonte prevailed, however a relative increase in demand from the surrounding area was observed. There was a reversal in the prevalence of morbidity switching from psychotic disorders to disorders resulting from the use of alcohol and/or other drugs. The alteration observed in the profile of treatment in public psychiatric hospitals in Belo Horizonte was concomitant with the progressive implementation of community mental health services, which have probably met the demand that was formerly directed to these hospitals. Currently the psychiatric hospital is not the first, much less the only venue for treatment in the mental health network in Minas Gerais. PMID- 25119102 TI - Anti-inflammatory activity of methanol extract and n-hexane fraction mojabanchromanol b from Myagropsis myagroides. AB - AIMS: This study was carried out to verify the anti-inflammatory effect of methanol extract from Myagropsis myagroides (MMME) and its n-hexane fraction mojabanchromanol b. MAIN METHODS: The murine macrophages Raw264.7 cells were used. The pro-inflammatory cytokines (IL-6, IL-1beta, TNF-alpha) and the expression of iNOS, COX-2, and NF-kappaB p65 were examined by ELISA and immunoblotting. To investigate the inhibitory effect of MMME in an animal model of inflammation, an assay to determine croton oil-induced ear edema in mice was performed. KEY FINDINGS: NO levels decreased with increasing concentration of MMME, and were inhibited up to 50%. The secretion of IL-6, TNF-alpha, and IL 1beta was suppressed in a dose-dependent manner, especially at 50MUg/mL, inhibition activities of cytokines were over 50%. MMME also suppressed the expression of COX-2, iNOS, and NF-kappaB p65, suggesting that MMME could affect the expression of inflammation related cytokines and proteins through the deregulation of NF-kappaB. Moreover, the formation of mouse ear edema was reduced at the highest dose tested compared to that in the control, and generated similar effects compared with prednisolone at 250mg/kg in mice ear edema evaluation test. In addition, the results in photomicrograph of mice ear tissue and mast cells also showed the same effect. After purification of fractions of MMME, it indicated that n-hexane fraction mojabanchromanol b was the most active fraction showing the inhibitory effect of IL-6 and TNF-alpha. SIGNIFICANCE: These results suggested that MMME and mojabanchromanol b may have great effects on inflammatory factors and be potential anti-inflammatory therapeutic materials. PMID- 25119103 TI - The effects of PTBP3 silencing on the proliferation and differentiation of MKN45 human gastric cancer cells. AB - AIMS: PTBP3 overexpression inhibits the differentiation of leukemia cells; however, its effects on the differentiation and proliferation of solid cancer cells remain unclear. Thus, the impact of PTBP3 on the differentiation and proliferation of gastric cancer cells was investigated. MAIN METHODS: PTBP3 expression was analyzed in normal and tumor tissues using immunohistochemistry. A xenograft model was established in nude mice by subcutaneous injection of untransfected human gastric cancer MKN45 cells or those expressing a control vector or PTBP3 siRNA. We analyzed the tumor inhibition rate, the expression of PTBP3, the PCNA-positive rate and the serum levels of CEA, CA199, CA125, LDH, ALP and gamma-GT in different groups. KEY FINDINGS: The tumor weights in the PTBP3 siRNA group were significantly lower than that of the MKN45 cell control group (P<0.001). Immunohistochemistry analysis of PCNA expression revealed that it was markedly reduced after PTBP3 silencing. ELISAs showed that the serum levels of CEA and CA199 tumor markers as well as LDH and ALP were reduced after PTBP3 silencing. Transmission electron microscopy revealed that MKN45 cells expressing PTBP3 siRNA had reduced nuclear-to-cytoplasmic ratio and regular nuclei, suggesting differentiation. SIGNIFICANCE: PTBP3 may promote proliferation and inhibit the differentiation of human gastric cancer MKN45 cells. PMID- 25119104 TI - Preparation, characterisation and bioactivity evaluation of the inclusion complex formed between picoplatin and gamma-cyclodextrin. AB - The inclusion complex of picoplatin with gamma-cyclodextrin (gamma-CD) was prepared and characterised by different analytical methods, including NMR, FTIR, TGA, phase solubility as well as SEM. All of these approaches indicated that picoplatin was able to form an inclusion complex with gamma-CD, and that the picoplatin/gamma-CD inclusion compounds exhibited different spectroscopic features and properties from free picoplatin. The stoichiometry of the complex was 1:1; the pyridine group of picoplatin was deeply inserted into the cavity of gamma-CD and the amine platinum group of picoplatin was near the narrower rim of gamma-CD. The calculated apparent stability constant of the complex was 10,318M( 1). Moreover, the water solubility of picoplatin was significantly improved, according to phase-solubility studies. The complex maintained its anticancer activity, as shown by an in vitro cell-survival assay on A549 and MCF-7 cancer cell lines. All of these results showed that inclusion complexation may be a promising strategy to design a novel formulation of picoplatin as an anticancer therapy. PMID- 25119105 TI - In vitro induced regulatory T cells are unique from endogenous regulatory T cells and effective at suppressing late stages of ongoing autoimmunity. AB - Strategies to boost the numbers and functions of regulatory T cells (Tregs) are currently being tested as means to treat autoimmunity. While Tregs have been shown to be effective in this role, strategies to manipulate Tregs to effectively suppress later stages of ongoing diseases need to be established. In this study, we evaluated the ability of TGF-beta-induced Tregs (iTregs) specific for the major self-antigen in autoimmune gastritis to suppress established autoimmune gastritis in mice. When transferred into mice during later stages of disease, iTregs demethylated the Foxp3 promoter, maintained Foxp3 expression, and suppressed effector T cell proliferation. More importantly, these iTregs were effective at stopping disease progression. Untreated mice had high numbers of endogenous Tregs (enTregs) but these were unable to stop disease progression. In contrast, iTregs, were found in relatively low numbers in treated mice, yet were effective at stopping disease progression, suggesting qualitative differences in suppressor functions. We identified several inhibitory receptors (LAG-3, PD-1, GARP, and TNFR2), cytokines (TGF-beta1 and IL12p35), and transcription factors (IRF4 and Tbet) expressed at higher levels by iTregs compared to enTregs isolated form mice with ongoing disease, which likely accounts for superior suppressor ability in this disease model. These data support efforts to use iTregs in therapies to treat establish autoimmunity, and show that iTregs are more effective than enTregs at suppressing inflammation in this disease model. PMID- 25119110 TI - Topological insulator states in a honeycomb lattice of s-triazines. AB - Two-dimensional (2D) graphitic carbon nitride materials have been drawing increasing attentions in energy conversion, environment protection and spintronic devices. Here, based on first-principles calculations, we demonstrate that the already-synthesized honeycomb lattice of s-triazines with a chemical formula of C6N6 (g-C6N6) has topologically nontrivial electronic states characterized by px,y-orbital band structures with a topological invariant of Z2 = 1, and stronger spin-orbital coupling (SOC) than both graphene and silicene. The band gaps opened in the px,y-orbital bands due to SOC are 5.50 meV (K points) and 8.27 eV (Gamma point), respectively, implying that the quantum spin Hall effect (QSHE) could be achieved in this 2D graphitic carbon nitride material at a temperature lower than 95 K. This offers a viable approach for searching for 2D Topological Insulators (TIs) in metal-free organic materials. PMID- 25119106 TI - The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation. AB - PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells. Here, we found that mice primary hematopoietic progenitor cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were deficient in colony formation. Further experiments showed that DNA-binding defective PML/RARA mutants could not repress the transcription of retinoic acid regulated genes. Intriguingly, there were no significant differences of the micro speckled intracellular distribution between the mutants and wild-type PML/RARA. Some retinoic acid target genes regulated by PML/RARA are involved in not only differentiation block but also hematopoietic cell self-renewal. Altogether, our data demonstrate that direct DNA-binding is essential for PML/RARA to immortalize hematopoietic cells, while disruption of PML-nuclear body does not seem to be a prerequisite for hematopoietic cell transformation. PMID- 25119111 TI - Integrating metalloporphycenes into p-type NiO-based dye-sensitized solar cells. AB - In the current work, we have explored a novel synthetic route towards metalated porphycenes and their use in p-type NiO-based dye-sensitized solar cells. Particular emphasis is placed on the influence that the relative positioning of the anchoring group exerts on the DSSC performance. PMID- 25119112 TI - Ionic-liquid-micelle-functionalized mesoporous Fe3O4 microspheres for ultraperformance liquid chromatography determination of anthraquinones in dietary supplements. AB - A magnetic solid-phase extraction method using ionic liquid (IL)-micelle functionalized mesoporous Fe3O4 microspheres (MFMs) was proposed for the preconcentration of anthraquinones in dietary supplements. The analytes were then determined by ultraperformance liquid chromatography combined with an ultraviolet detector. The extraction parameters, such as the choice of ILs, the concentrations of ILs and MFMs, the pH of diluent, and the concentration of acetic acid in the eluent, were presented. Under the optimized conditions, the limits of detection and limits of quantitation were 0.4-2.8 ng mL(-1) and 1.4-9.4 ng mL(-1), respectively. The accuracy of the proposed method was investigated by recovery in herb and granules of Radix et Rhizoma Rhei, yielding values between 89.25% and 96.48%. The use of the proposed method in the sample pretreatment of complex dietary supplements is feasible due to the high surface area and excellent adsorption capacity of MFMs after modification with IL. PMID- 25119107 TI - Risk factors and adverse perinatal outcomes among term and preterm infants born small-for-gestational-age: secondary analyses of the WHO Multi-Country Survey on Maternal and Newborn Health. AB - BACKGROUND: Small for gestational age (SGA) is not only a major indicator of perinatal mortality and morbidity, but also the morbidity risks in later in life. We aim to estimate the association between the birth of SGA infants and the risk factors and adverse perinatal outcomes among twenty-nine countries in Africa, Latin America, the Middle East and Asia in 359 health facilities in 2010-11. METHODS: We analysed facility-based, cross-sectional data from the WHO Multi country Survey on Maternal and Newborn Health. We constructed multilevel logistic regression models with random effects for facilities and countries to estimate the risk factors for SGA infants using country-specific birthweight reference standards in preterm and term delivery, and SGA's association with adverse perinatal outcomes. We compared the risks and adverse perinatal outcomes with appropriate for gestational age (AGA) infants categorized by preterm and term delivery. RESULTS: A total of 295,829 singleton infants delivered were analysed. The overall prevalence of SGA was highest in Cambodia (18.8%), Nepal (17.9%), the Occupied Palestinian Territory (16.1%), and Japan (16.0%), while the lowest was observed in Afghanistan (4.8%), Uganda (6.6%) and Thailand (9.7%). The risk of preterm SGA infants was significantly higher among nulliparous mothers and mothers with chronic hypertension and preeclampsia/eclampsia (aOR: 2.89; 95% CI: 2.55-3.28) compared with AGA infants. Higher risks of term SGA were observed among sociodemographic factors and women with preeclampsia/eclampsia, anaemia and other medical conditions. Multiparity (> = 3) (AOR: 0.88; 95% CI: 0.83-0.92) was a protective factor for term SGA. The risk of perinatal mortality was significantly higher in preterm SGA deliveries in low to high HDI countries. CONCLUSION: Preterm SGA is associated with medical conditions related to preeclampsia, but not with sociodemographic status. Term SGA is associated with sociodemographic status and various medical conditions. PMID- 25119114 TI - Syntheses and structures of copper complexes of 3-(6-(1H-pyrazol-1-yl)pyridin-2 yl)pyrazol-1-ide and their excellent performance in the syntheses of nitriles and aldehydes. AB - Reactions of a pincer ligand 2-(1H-pyrazol-1-yl)-6-(1H-pyrazol-3-yl)pyridine (pzpypzH) with Cu(NO3)2, Cu(ClO4)2, CuSO4, CuCl2 or CuI produced three dinuclear Cu(ii) complexes [{Cu(NO3)}(MU-pzpypz)]2 (1), [{Cu(ClO4)}(MU-pzpypz)]2 (2), [Cu2(MU-SO4)(MU-pzpypz)2].2MeOH (3.2MeOH), one mononuclear Cu(ii) complex [CuCl2(pzpypzH)] (4) and one trinuclear Cu(i)/Cu(ii) complex [(ICu)(MU-I)2Cu2(MU pzpypz)2] (5), respectively. Treatment of 4 with two equiv. of AgNO3 in DMF also gave rise to 1. Complexes 1-5 were characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. Complex 1 or 2 has a dimeric structure in which two {Cu(X)} (X = NO3, ClO4) fragments are interconnected by two MU-pzpypz(-) ligands. 3 also adopts a dimeric structure in which two Cu(ii) centers are interconnected by a pair of MU-pzpypz(-) ligands and one MU-SO4(2-) ion. The Cu(ii) center in 4 is five-coordinated by three N atoms of the pzpypzH ligand and two Cl atoms. In 5, two Cu(ii) centers are bridged by two MU-pzpypz(-) ligands and one CuI3(2-) unit, forming a unique trinuclear structure. Complexes 1 5 displayed high catalytic activity toward the ammoxidation of alcohols to nitriles and the aerobic oxidation of alcohols to aldehydes in H2O. The nitrile or aldehyde products could be readily separated from the catalytic system by extraction and the residual aqueous solution containing 1 retained good activity for several cycles. PMID- 25119115 TI - Electrochemical behavior of the 1,10-phenanthroline ligand on a multiwalled carbon nanotube surface and its relevant electrochemistry for selective recognition of copper ion and hydrogen peroxide sensing. AB - 1,10-Phenanthroline (Phen) is a well-known benchmark ligand and has often been used in the coordination chemistry for the complexation of transition metal ions, such as Fe(2+), Ni(2+), and Co(2+). Because the electro-oxidation potential of Phen is much higher (>2 V versus Ag/AgCl) than the water decomposition potential, i.e., ~1.5 V versus Ag/AgCl, in pH 7, it is practically difficult to electro oxidize Phen in aqueous medium using any conventional electrodes, such as glassy carbon electrode (GCE), gold, and platinum. Interestingly, herein, we report an unexpected oxidation of Phen to a highly redox active 1,10-phenanthroline-5,6 dione (Phen-dione) and its confinement on a multiwalled carbon nanotube (MWCNT) modified glassy carbon electrode (GCE/MWCNT@Phen-dione) surface by potential cycling of Phen-adsorbed GCE/MWCNT (GCE/MWCNT@Phen) from -1 to 1 V versus Ag/AgCl in pH 7 phosphate buffer solution. GCE/MWCNT@Phen-dione showed selective recognition of copper ion (GCE/MWCNT@Phen-dione-Cu(2+)) by catalyzing the hydrogen peroxide reduction reaction in a neutral pH solution. The precise structure of the Phen electro-oxidized product has been identified after characterizing the electrode and/or ethanolic extract of the product by various techniques, such as Raman, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) (for copper complex), liquid chromatography-mass spectrometry (LC-MS), electrospray ionization-mass spectrometry (ESI-MS) (for copper complex), cyclic voltammetry (CV), and in situ electrochemical quartz crystal microbalance (EQCM) and comparing electrochemical behavior of several control compounds, such as phenanthrene and 9,10-phenanthrenequinone. It is concluded that the product formed is 1,10-phenanthroline-5,6-dione, wherein the dione position is ortho to each other and the copper ion is complexed with nitrogen of the phenanthroline ring. With extended electrochemical oxidation of a structurally similar ligand, 2,2'-bipyridine failed to show any such electrochemical dynamics. Finally, applicability of GCE/MWCNT@Phen-dione-Cu(2+) for electrochemical sensing of hydrogen peroxide in a couple of real samples is successfully demonstrated. PMID- 25119113 TI - Identification and association of the single nucleotide polymorphisms, C-509T, C+466T and T+869C, of the TGF-beta1 gene in patients with asthma and their influence on the mRNA expression level of TGF-beta1. AB - Transforming growth factor-beta1 (TGF-beta1) is an important fibrogenic and immunomodulatory cytokine participating in the pathogenesis of a number of illnesses related to the growth, differentiation and migration of cells. It also plays a key role in inflammation, atherosclerosis, vascular inflammation and asthma. The aim of the present study was to evaluate the association between the expression of the TGF-beta1 gene and its genetic polymorphisms, and the disease phenotype. The study comprised 173 patients with asthma, as well as 163 healthy volunteers as a control group. The gender profiles of the groups were similar (p=0.8415). Genotyping was performed by polymerase chain reaction (PCR)-high resolution melting (HRM). The results were verified by sequencing. Gene expression was evaluated by RT-PCR. This study evaluated the role and frequency of genetic polymorphisms (C-509T, C+466T and T+869C) of the TGF-beta1 gene in the study group (patients with asthma) and the control group (healthy volunteers). The results obtained for the patients and healthy controls were as follows: C 509T single nucleotide polymorphism (SNP) (controls, TT/CT/CC 0.4444/0.5309/0.0247; patients, TT/CT/CC-0.3699/0.6012/0.0289), C+466T SNP (controls, TT/CT/CC-1.000/0.000/0.000; patients, TT/CT/CC-1.000/0.000/0.000) and T+869C SNP (controls, TT/CT/CC-1.000/0.000/0.000; patients, TT/CT/CC 1.000/0.000/0.000). Only the C-509T polymorphism was found to play a significant role in the pathogenesis of asthma, as well as a risk factor in the loss of the clinical control of the disease [TT vs. CC/CT, odds ratio (OR) 2.38; confidence interval (CI) 1.22-4.66; p=0.0103]. A significant difference was noted between the study and control groups with regard to the mRNA expression of TGF-beta1 (p=0.0133). A higher level of expression of the TGF-beta1 gene correlated with the time of diagnosis of patients over 16 years of age (p=0.0255). This study demonstrates that the C-509T SNP is a significant clinical risk factor for asthma and that the TGF-beta1 cytokine contributes to the progression of the illness. PMID- 25119116 TI - Comparison of two non-mydriatic fundus cameras to obtain retinal arterio-venous ratio. AB - PURPOSE: To analyze device-dependent variability of two non-mydriatic fundus cameras to obtain arterio-venous ratio (AVR), central retinal arteriolar equivalent (CRAE), and central retinal venular equivalent (CRVE) in static vessel analysis (SVA). METHODS: We examined 53 participants (29 men, 24 women; median age 46 years) of the Study of Health in Pomerania (SHIP). We took 45 degrees optic-disc-centered fundus images of the right eye with two different non mydriatic fundus cameras. The first photograph was obtained from the TRC-NW 200, the second from the OCT 2000 (both Topcon Corporation, Tokyo, Japan). One experienced grader graded image quality from 1 "ideal quality" to 5 "not analyzable" and determined AVR, CRAE, and CRVE with the software Vesselmap3 (Imedos, Jena, Germany). RESULTS: Average image quality was 1.8 for the TRC-NW 200 and 1.6 for the OCT 2000. AVR could not be determined in 5 images of the TRC NW 200 due to low image quality, while six images of the OCT 2000 were not analyzable. The difference between AVR taken from two different non-mydriatic cameras was 0.01 +/- 0.03 in Bland-Altman plots. The difference between CRAE was 0.17 +/- 10.15 and between CRVE was -2.32 +/- 11.76. CONCLUSIONS: The two different non-mydriatic cameras showed good agreement with respect to image quality. When using the same reading software, AVR, CRAE, and CRVE agreed well. Thus, funduscopy and SVA seem to be robust against inter-device variability. As a result, device dependency can remain unconsidered in follow-up examinations with different technical equipment. However, variability might impact more with devices from different manufacturers. PMID- 25119117 TI - Randomized clinical trial on epidural versus patient-controlled analgesia for laparoscopic colorectal surgery within an enhanced recovery pathway. AB - OBJECTIVE: To compare epidural analgesia (EDA) to patient-controlled opioid-based analgesia (PCA) in patients undergoing laparoscopic colorectal surgery. BACKGROUND: EDA is mainstay of multimodal pain management within enhanced recovery pathways [enhanced recovery after surgery (ERAS)]. For laparoscopic colorectal resections, the benefit of epidurals remains debated. Some consider EDA as useful, whereas others perceive epidurals as unnecessary or even deleterious. METHODS: A total of 128 patients undergoing elective laparoscopic colorectal resections were enrolled in a randomized clinical trial comparing EDA versus PCA. Primary end point was medical recovery. Overall complications, hospital stay, perioperative vasopressor requirements, and postoperative pain scores were secondary outcome measures. Analysis was performed according to the intention-to-treat principle. RESULTS: Final analysis included 65 EDA patients and 57 PCA patients. Both groups were similar regarding baseline characteristics. Medical recovery required a median of 5 days (interquartile range [IQR], 3-7.5 days) in EDA patients and 4 days (IQR, 3-6 days) in the PCA group (P = 0.082). PCA patients had significantly less overall complications [19 (33%) vs 35 (54%); P = 0.029] but a similar hospital stay [5 days (IQR, 4-8 days) vs 7 days (IQR, 4.5-12 days); P = 0.434]. Significantly more EDA patients needed vasopressor treatment perioperatively (90% vs 74%, P = 0.018), the day of surgery (27% vs 4%, P < 0.001), and on postoperative day 1 (29% vs 4%, P < 0.001), whereas no difference in postoperative pain scores was noted. CONCLUSIONS: Epidurals seem to slow down recovery after laparoscopic colorectal resections without adding obvious benefits. EDA can therefore not be recommended as part of ERAS pathways in laparoscopic colorectal surgery. PMID- 25119118 TI - Assessing Technical Competence in Surgical Trainees: A Systematic Review. AB - OBJECTIVE: To systematically examine the literature describing the methods by which technical competence is assessed in surgical trainees. BACKGROUND: The last decade has witnessed an evolution away from time-based surgical education. In response, governing bodies worldwide have implemented competency-based education paradigms. The definition of competence, however, remains elusive, and the impact of these education initiatives in terms of assessment methods remains unclear. METHODS: A systematic review examining the methods by which technical competence is assessed was conducted by searching MEDLINE, EMBASE, PsychINFO, and the Cochrane database of systematic reviews. Abstracts of retrieved studies were reviewed and those meeting inclusion criteria were selected for full review. Data were retrieved in a systematic manner, the validity and reliability of the assessment methods was evaluated, and quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation classification. RESULTS: Of the 6814 studies identified, 85 studies involving 2369 surgical residents were included in this review. The methods used to assess technical competence were categorized into 5 groups; Likert scales (37), benchmarks (31), binary outcomes (11), novel tools (4), and surrogate outcomes (2). Their validity and reliability were mostly previously established. The overall Grading of Recommendations Assessment, Development and Evaluation for randomized controlled trials was high and low for the observational studies. CONCLUSIONS: The definition of technical competence continues to be debated within the medical literature. The methods used to evaluate technical competence predominantly include instruments that were originally created to assess technical skill. Very few studies identify standard setting approaches that differentiate competent versus noncompetent performers; subsequently, this has been identified as an area with great research potential. PMID- 25119119 TI - Glycopeptides versus beta-lactams for the prevention of surgical site infections in cardiovascular and orthopedic surgery: a meta-analysis. AB - OBJECTIVE: To compare the efficacy of glycopeptides and beta-lactams in preventing surgical site infections (SSIs) in cardiac, vascular, and orthopedic surgery. BACKGROUND: The cost-effectiveness of switching from beta-lactams to glycopeptides for preoperative antibiotic prophylaxis has been controversial. beta-Lactams are generally recommended in clean surgical procedures, but they are ineffective against resistant gram-positive bacteria. METHODS: PubMed, International Pharmaceuticals Abstracts, Scopus, and Cochrane were searched for randomized clinical trials comparing glycopeptides and beta-lactams for prophylaxis in adults undergoing cardiac, vascular, or orthopedic surgery. Abstracts and conference proceedings were included. Two independent reviewers performed study selection, data extraction, and assessment of risk of bias. RESULTS: Fourteen studies with a total of 8952 patients were analyzed. No difference was detected in overall SSIs between antibiotic types. However, compared with beta-lactams, glycopeptides reduced the risk of resistant staphylococcal SSIs by 48% (relative risk, 0.52; 95% confidence interval, 0.29 0.93; P = 0.03) and enterococcal SSIs by 64% (relative risk, 0.36; 95% confidence interval, 0.16-0.80; P = 0.01), but increased respiratory tract infections by 54% (relative risk, 1.54; 95% confidence interval, 1.19-2.01; P <= 0.01). Subgroup analysis of cardiac procedures showed superiority of beta-lactams in preventing superficial and deep chest SSIs, susceptible staphylococcal SSIs, and respiratory tract infections. CONCLUSIONS: Glycopeptides reduce the risk of resistant staphylococcal SSIs and enterococcal SSIs, but increase the risk of respiratory tract infections. Additional high-quality randomized clinical trials are needed as these results are limited by high risk of bias. PMID- 25119120 TI - Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus nonabsorbable mesh: a randomized controlled trial. AB - OBJECTIVE: Determine whether absorbable or nonabsorbable mesh in repair of large hiatus hernias reduces the risk of recurrence, compared with suture repair. BACKGROUND: Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%, and to improve outcomes mesh repair has been recommended. Previous trials have shown less short-term recurrence with mesh, but adverse outcomes limit mesh use. METHODS: Multicentre prospective double blind randomized controlled trial of 3 methods of repair: sutures versus absorbable mesh versus nonabsorbable mesh. Primary outcome-hernia recurrence assessed by barium meal radiology and endoscopy at 6 months. Secondary outcomes-clinical symptom scores at 1, 3, 6, and 12 months. RESULTS: A total of 126 patients enrolled: 43 sutures, 41 absorbable mesh, and 42 nonabsorbable mesh. Among them, 96.0% were followed up to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any size) was identified in 23.1% after suture repair, 30.8% after absorbable mesh, and 12.8% after nonabsorbable mesh (P = 0.161). Clinical outcomes were similar, except less heartburn at 3 and 6 months and less bloating at 12 months with nonabsorbable mesh; more heartburn at 3 months, odynophagia at 1 month, nausea at 3 and 12 months, wheezing at 6 months; and inability to belch at 12 months after absorbable mesh. The magnitudes of the clinical differences were small. CONCLUSIONS: No significant differences were seen for recurrent hiatus hernia, and the clinical differences were unlikely to be clinically significant. Overall outcomes after sutured repair were similar to mesh repair. PMID- 25119121 TI - Indeterminate Pulmonary Nodules in Colorectal Cancer: Follow-up Guidelines Based on a Risk Predictive Model. AB - BACKGROUND: Chest computed tomographic (CT) scans frequently detect indeterminate pulmonary nodules (IPNs) in patients with colorectal cancer. The discovery of such nodules creates a clinical dilemma. PURPOSE: This study was performed to identify clinical characteristics of IPNs and develop a predictive model to predict the risk of progression to pulmonary metastases in patients with colorectal cancer. METHODS: We analyzed data from a prospectively collected database involving 1195 patients with colorectal carcinoma who underwent curative surgery between January 2008 and June 2010. A predictive model was constructed on the basis of the probability risk score and validated in 115 patients collected from a separate treatment period. RESULTS: Of the 1195 patients who underwent a baseline staging chest computed tomography, 326 (27.2%) had IPNs. During a median follow-up of 26.7 months (interquartile range: 18.0-37.2), 74 (28.1%) showed pulmonary metastases. Five variables maintained prognostic significance after multivariate analysis: metachronous nodule, bilateral involvement, positive perineural invasion, increased number of positive lymph nodes, and rectal location of cancer. The 2-year progression-free survival rates for the very low-, low-, intermediate-, and high-risk groups were 96%, 82%, 46%, and 16%, respectively (P < 0.001), with a concordance index of 0.81 (95% confidence interval, 0.75-0.86). This model was validated in a separate patient set (P < 0.001), with a C-index of 0.83 (95% confidence interval, 0.77-0.88). CONCLUSIONS: A predictive model for progression of IPNs may be clinically useful in discriminating patients who might benefit from an aggressive surveillance program and early pulmonary metastasectomies. PMID- 25119122 TI - Abdominoperineal resection provides better local control but equivalent overall survival to local excision of anorectal malignant melanoma: a systematic review. AB - OBJECTIVE: To determine whether the extent of surgery is associated with survival in anorectal malignant melanoma (ARMM). BACKGROUND: ARMM is a rare and highly malignant neoplasm with unfavorable prognosis. The optimal surgical management, abdominoperineal resection (APR) or local excision (LE), has been long debated, but conclusive evidence has not been obtained. METHODS: A comprehensive electronic literature search was performed to identify studies evaluating survival between APR and LE for ARMM. The main outcome measures were overall survival, relapse-free survival, and local recurrence. A meta-analysis was performed using the random-effects models to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Thirty-one studies, with a total of 1006 patients [544 (54.1%) APR and 462 (45.9%) LE], were included. Meta-analyses showed that overall survival (OR, 1.14; 95% CI, 0.74-1.76; P = 0.54) and relapse free survival (OR, 0.95; 95% CI, 0.43-2.09; P = 0.89) did not differ significantly between the APR and LE groups. APR significantly reduced local recurrence compared with LE (OR, 0.18; 95% CI, 0.09-0.36; P < 0.00001). CONCLUSIONS: Although several limitations, such as inclusion of only retrospective studies with relatively small sample size and selection biases for surgical procedure, are involved, this meta-analysis suggested that APR has no survival benefit; however, APR confers better local control than LE. Given that local failures after LE could be managed by salvage surgery, minimizing morbidity and maximizing quality of life should be the focus in surgical treatment of ARMM. PMID- 25119123 TI - Postoperative venous thromboembolism outcomes measure: analytic exploration of potential misclassification of hospital quality due to surveillance bias. PMID- 25119124 TI - Natural promoters of calcium oxalate monohydrate crystallization. AB - Crystallization is often facilitated by modifiers that interact with specific crystal surfaces and mediate the anisotropic rate of growth. Natural and synthetic modifiers tend to function as growth inhibitors that hinder solute attachment and impede the advancement of layers on crystal surfaces. There are fewer examples of modifiers that operate as growth promoters, whereby modifier crystal interactions accelerate the kinetic rate of crystallization. Here, we examine two proteins, lysozyme and lactoferrin, which are observed in the organic matrix of three types of pathological stones: renal, prostatic, and pancreatic stones. This work focuses on the role of these proteins in the crystallization of calcium oxalate monohydrate (COM), the most prominent constituent of human kidney stones. Using a combination of experimental techniques, we show that these proteins, which are rich in l-arginine and l-lysine amino acids, promote COM growth. The synthesis and testing of peptides derived from contiguous segments of lysozyme's primary amino acid sequence revealed subdomains within the protein that operate either as an inhibitor or promoter of COM growth, with the latter exhibiting efficacies that nearly match that of the protein. We observed that cationic proteins promote COM growth over a wide range of modifier concentration, which differs from calcification promoters in the literature that exhibit dual roles as promoters and inhibitors at low and high concentration, respectively. This seems to suggest a unique mechanism of action for lysozyme and lactoferrin. Possible explanations for their effects on COM growth and crystal habit are proposed on the basis of classical colloidal theories and the physicochemical properties of peptide subdomains, including the number and spatial location of charged or hydrogen-bonding moieties. PMID- 25119125 TI - Factors behind negative attitudes toward cadaveric organ donation: a comparison between medical and non-medical students in China: retraction. PMID- 25119126 TI - National assessment of early biliary complications after liver transplantation: economic implications. AB - BACKGROUND: Despite improvement in surgical technique and medical management of liver transplant recipients, biliary complications remain a frequent cause of posttransplant morbidity and graft loss. Biliary complications require potentially expensive interventions including radiologic procedures and surgical revisions. METHODS: A national data set linking transplant registry and Medicare claims data for 12,803 liver transplant recipients was developed to capture information on complications, treatments, and associated direct medical costs up to 3 years after transplantation. RESULTS: Biliary complications were more common in recipients of donation after cardiac death compared to donation after brain death allografts (23% vs. 19% P<0.001). Among donation after brain death recipients, biliary complications were associated with $54,699 (95% confidence interval [CI], $49,102 to $60,295) of incremental spending in the first year after transplantation and $7,327 in years 2 and 3 (95% CI, $4,419-$10,236). Biliary complications in donation after cardiac death recipients independently increased spending by $94,093 (95% CI, $64,643-$124,542) in the first year and $12,012 (95% CI, $-1,991 to $26,016) in years 2 and 3. CONCLUSION: This national study of biliary complications demonstrates the significant economic impact of this common perioperative complication and suggests a potential target for quality of care improvements. PMID- 25119127 TI - Time-to-referral, use, and efficacy of cardiac rehabilitation after heart transplantation. AB - BACKGROUND: Timely access, adherence, and efficacy of cardiac rehabilitation programs (CRP) are important given the potential to mitigate or reverse the side effects of immunosuppressive medications, weight gain, and cardiovascular deconditioning that place heart transplant (HT) recipients at increased cardiovascular risk. However, there is a dearth of information on use and efficacy of CRPs. Therefore, we examined process indicators (time to referral and correlates, program adherence) and clinical outcome indicators (functional capacity (VO(2peak)), anthropometrics) of CR post-HT compared to post-coronary artery bypass graft (CABG). METHODS: Baseline, 6-month exercise stress test results, and anthropometrics were examined retrospectively among consecutively enrolled post-HT and age-matched and sex-matched CABG patients. Time to referral and program entry, attendance, and completion rates were also measured. RESULTS: Heart transplant (n=43) and CABG patients were referred 24.9 +/- 48.9 and 2.1 +/- 3.6 months, respectively, after surgery (P=0.003). Once referred, there was no difference in elapsed-time to program entry (P=0.2). There was a positive relationship between time to referral and baseline waist circumference (r=0.5, P=0.001), body mass index (r=0.5, P=0.002), hip circumference (r=0.4, P=0.008), and body fat percentage (r=0.4, P=0.03) in HT. Heart transplant and CABG patients had similar rates of CRP dropout (27.9% vs. 37.2% respectively, P=0.4). There was improvement in VO(2peak) for HT (2.4 +/- 4.2 mL/kg/min; P=0.02) and CABG (5.5 +/- 5.4 mL/kg/min, P<0.001), but was greater for CABG (P=0.04). Anthropometric measures remained stable for both cohorts (P>0.05). CONCLUSION: There is a lengthy delay in time from HT to CRP referral, though once referred, gain significant benefit in functional capacity. The appropriateness of this wait needs to be elucidated; however, it appears that longer wait times are associated with adverse effects on body composition. PMID- 25119129 TI - The preferences and perspectives of nephrologists on patients' access to kidney transplantation: a systematic review. AB - We aimed to describe nephrologists' attitudes to patients' access to kidney transplantation. Studies that assessed nephrologists' perspectives toward patient referral, screening, and eligibility for kidney transplantation were synthesized. Twenty-four studies (n>=4695) were included. Patients with comorbidities, were nonadherent, of older age, ethnic minorities, or low socioeconomic status were less likely to be recommended. Six themes underpinned nephrologists' perspectives: prioritizing individual benefit and safety, maximizing efficiency, patient accountability, justifying gains, protecting unit outcomes, and reluctance to raise patients' expectations. Evidence-based guidelines may support systematic and equitable decision-making. Interventions for high-risk or disadvantaged patient populations could reduce disparities in access to transplantation. PMID- 25119128 TI - Lung transplantation for severe pulmonary hypertension--awake extracorporeal membrane oxygenation for postoperative left ventricular remodelling. AB - BACKGROUND: Bilateral lung transplantation (BLTx) is an established treatment for end-stage pulmonary hypertension (PH). Ventilator weaning failure and death are more common as in BLTx for other indications. We hypothesized that left ventricular (LV) dysfunction is the main cause of early postoperative morbidity or mortality and investigated a weaning strategy using awake venoarterial extracorporeal membrane oxygenation (ECMO). METHODS: In 23 BLTx for severe PH, ECMO used during BLTx was continued for a minimum of 5 days (BLTx-ECMO group). Echocardiography, left atrial (LA) and Swan-Ganz catheters were used for monitoring. Early extubation after transplantation was attempted under continued ECMO. RESULTS: Preoperatively, all patients had severely reduced cardiac index (mean, 2.1 L/min/m2). On postoperative day 2, reduction of ECMO flow resulted in increasing LA and decreasing systemic blood pressures. On the day of ECMO explantation (median, postoperative day 8), LV diameter had increased; LA and blood pressures remained stable. Survival rates at 3 and 12 months were 100% and 96%, respectively. Data were compared to two historic control groups of BLTx without ECMO (BLTx ventilation) or combined heart-lung transplantation for severe PH. CONCLUSION: Early after BLTx for severe PH, the LV may be unable to handle normalized LV preload. This can be effectively bridged with awake venoarterial ECMO. PMID- 25119130 TI - Extensively drug-resistant Pseudomonas aeruginosa bacteremia in solid organ transplant recipients. AB - BACKGROUND: We sought to determine the risk factors, molecular epidemiology, antibiotic therapy, and outcomes of bacteremia because of extensively drug resistant (XDR) Pseudomonas aeruginosa in solid organ transplant (SOT) recipients. METHODS: All episodes of bacteremia occurring in SOT recipients were prospectively documented from 2007 to 2013. RESULTS: Of 318 episodes of bacteremia, 49 were caused by P. aeruginosa. Thirty-one strains (63%) were XDR defined by nonsusceptibility to at least one agent in all but two or fewer antipseudomonal antimicrobial categories. Time from transplantation to bacteremia was shorter in XDR P. aeruginosa group comparing to other etiologies (median days 66 vs. 278; P=0.03). Factors independently associated with XDR P. aeruginosa bacteremia were prior transplantation, nosocomial acquisition, and septic shock at onset. XDR P. aeruginosa isolates belonged to a single clone (ST-175). Comparing to other etiologies, patients with bacteremia because of XDR P. aeruginosa more often received inadequate empirical antibiotic therapy. Persistence of bacteremia, shock, respiratory failure and intensive care unit admission were more frequent in patients with XDR P. aeruginosa. The overall case fatality rate was higher among patients with XDR P. aeruginosa bacteremia than in the others (38% vs. 16%; P=0.009). CONCLUSION: Bacteremia because of XDR P. aeruginosa should be carefully considered when selecting empirical antibiotic therapy for hospitalized SOT recipients with prior transplantation presenting with septic shock. PMID- 25119131 TI - The risk of cancer in recipients of living-donor, standard and expanded criteria deceased donor kidney transplants: a registry analysis. AB - BACKGROUND: Kidneys from expanded criteria deceased donors may elicit a strong inflammatory response, predisposing recipients to an increased risk of cancer after transplantation. We aimed to determine the association between donor types and cancer risk after kidney transplantation. METHODS: Using the Australian and New Zealand Dialysis and Transplant Registry, we assessed the association between different donor types (living donor, standard, and expanded criteria deceased donors) and the risk of cancer after kidney transplantation using adjusted Cox proportional hazard and competing risk models. RESULTS: Over a median follow-up period of 4.4 years in 7,040 patients (34,684 patient-years), 468 patients (6.6%) developed cancer. The overall risks for cancer were 1,080, 1,444, and 2,018 per 100,000 patient-years for recipients of living donor, standard, and expanded criteria deceased donor kidneys, respectively. Compared to recipients of living donor kidneys, recipients of expanded criteria deceased donor kidneys were at an increased risk of cancer (adjusted hazard ratio [HR], 1.52; 95% confidence interval [95% CI], 1.15-2.02; P = 0.004), particularly for genitourinary cancer (adjusted HR, 1.79; 95% CI, 1.03-3.10; P = 0.038) and post-transplant lymphoproliferative disease (adjusted HR, 2.72; 95% CI, 1.38-5.37; P = 0.004). CONCLUSION: Recipients of expanded criteria deceased donor kidneys are at substantially increased risk of cancer, especially cancers with a viral etiology. Allocation of expanded criteria deceased donor kidneys to potential recipients should balance the harms, such as the excess risk of cancer against the survival gains and quality-of-life benefits associated with transplantation. PMID- 25119132 TI - Changes in circulating endothelial cells count could become a valuable tool in the diagnostic definition of acute graft-versus-host disease. AB - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is burdened by life-threatening complications, with graft-versus-host disease (GvHD) being the major cause of morbility and mortality. Recently, clinical and physiopathologic evidences showed that vascular endothelium can be a target of GvHD in the early phase and circulating endothelial cells (CECs) represent surrogate markers of endothelial damage. METHODS: Using the CellSearch System (Veridex LLC, Raritan, NJ), CECs were counted before (T1), after conditioning regimen (T2), at engraftment (T3), at GvHD onset (T4), and after steroid treatment (T5) in 40 patients (7 Hodgkin's Disease, 13 Acute Myeloblastic Leukemia, 5 Acute Lymphoblastic Leukemia, 8 Multiple Myeloma, 3 Chronic Lymphocytic Leukemia, 1 Non-Hodgkin Lymphoma, 1 Chronic Myeloid Leukemia, 2 Severe Aplastic Anemia) undergoing allo-HSCT. RESULTS: The median CEC per milliliter at T1 was 20 (n=33, range 4-718), in comparison to a value of 2 (range, 1-14) in controls (P<0.001). At T3, CEC per milliliter were 47 (range, 16 148) in GvHD patients and 92 (range, 23-276) in patients without GvHD (P=0.006). This difference remained significant in multivariate analysis (odds ratio, 0.97; 95% confidence interval, 0.96-0.99; P=0.02). At GvHD onset, the relative increase of CEC counts from time of engraftment (T4 vs. T3) was 44% (range, -43% to 569%) in GvHD patients versus 0% (range, -49% to 2%) in patients without GvHD (P=0.003), being confirmed as significant in multivariate analysis (odds ratio, 1.04; 95% confidence interval, 1.0-1.08; P=0.04). CONCLUSION: Changes in CEC count can represent a promising marker to monitor endothelial damage in patients undergoing allo-HSCT and could become a valuable tool in the diagnostic definition of GvHD. PMID- 25119133 TI - A novel simple noninvasive index to predict renal transplant acute rejection by contrast-enhanced ultrasonography. AB - PURPOSE: This study aimed to evaluate the application of quantitative contrast enhanced ultrasonography (CEUS) in the assessment of renal allograft dysfunction and to establish a new noninvasive index to predict acute rejection (AR). METHODS: Fifty-seven renal transplant recipients were enrolled in this prospective study. Before renal allograft biopsy, CEUS examinations were performed.The biopsy results proved 23 cases of AR (AR group), 10 cases of acute tubular necrosis (ATN group), and 24 with normal evolution (stable group). Contrast-enhanced ultrasonography parameters including rising time (RT), time to peak (TTP), and the delta-time among regions of interest (DeltaRT and DeltaTTP) were analyzed. RESULTS: In the AR group, RT and TTP of interlobar artery and medulla (RTi, RTm, TTPi, and TTPm) as well as DeltaRT and DeltaTTP between medulla and cortex (DeltaRTm-c and DeltaTTPm-c) were significantly higher compared with those in the stable group. RTm and TTPm as well as DeltaRTm-c and DeltaTTPm-c were remarkably higher compared with those in the ATN group. DeltaRTm c and estimated glomerular filtration rate (eGFR) were identified as independent predictors by multivariate analysis (P = 0.008 and P = 0.024). On the basis of the multivariate analysis results and area under the receiver operating characteristic curves of individual markers, we constructed a new simple index, P = -0.587 + 0.286 *DeltaRTm-c - 0.028 * eGFR; new index = e(P)/(1 + e(P)), to discriminate AR, which had better area under the receiver operating characteristic curves than eGFR or individual CEUS parameters. CONCLUSION: Contrast-enhanced ultrasonography parameters are reliable markers for differentiating the perfusion status of transplanted kidneys. Furthermore, the new simple index can easily predictAR with a high degree of accuracy. PMID- 25119135 TI - Ion pairing: from water clusters to the aqueous bulk. PMID- 25119134 TI - The outcomes of simultaneous liver and kidney transplantation using donation after cardiac death organs. AB - BACKGROUND: There has been a remarkable increase in simultaneous liver and kidney transplantations (SLK). As organ demand has increased, so has the use of donation after cardiac death (DCD). However, little is known about the outcomes of DCD in SLK. METHODS: We performed a retrospective analysis using the United Network for Organ Sharing database to compare the outcomes of DCD SLK to donation after brain death (DBD) and determine the impact of donor and recipient factors on allograft and patient survival. RESULTS: Between 2002 and 2011, a total of 3,026 subjects received SLK from DBD and 98 from DCD. Kidney, liver, and patient survival from DCD donors were inferior to DBD at 1, 3, and 5 years (P=0.0056, P=0.0035, and P=0.0205, respectively). With the use of the Cox model, DCD was a significant risk factor for kidney and liver allograft failure and patient mortality. Recipient factors that were associated with worse allograft and patient outcomes included black race, diabetes, being on a ventilator, hospitalization, delayed graft function, hepatocellular carcinoma, and intensive care unit stay. Older age of the donor was also associated with worse outcomes. CONCLUSION: Despite the decreased allograft and patient survival compared with DBD, DCD SLK provides an acceptable option for SLK, with a survival probability of more than 50% at 5 years. PMID- 25119136 TI - The p53-reactivating small molecule RITA induces senescence in head and neck cancer cells. AB - TP53 is the most commonly mutated gene in head and neck cancer (HNSCC), with mutations being associated with resistance to conventional therapy. Restoring normal p53 function has previously been investigated via the use of RITA (reactivation of p53 and induction of tumor cell apoptosis), a small molecule that induces a conformational change in p53, leading to activation of its downstream targets. In the current study we found that RITA indeed exerts significant effects in HNSCC cells. However, in this model, we found that a significant outcome of RITA treatment was accelerated senescence. RITA-induced senescence in a variety of p53 backgrounds, including p53 null cells. Also, inhibition of p53 expression did not appear to significantly inhibit RITA-induced senescence. Thus, this phenomenon appears to be partially p53-independent. Additionally, RITA-induced senescence appears to be partially mediated by activation of the DNA damage response and SIRT1 (Silent information regulator T1) inhibition, with a synergistic effect seen by combining either ionizing radiation or SIRT1 inhibition with RITA treatment. These data point toward a novel mechanism of RITA function as well as hint to its possible therapeutic benefit in HNSCC. PMID- 25119137 TI - Topical, Non-Medicated LOYON((r)) in Facilitating the Removal of Scaling in Infants and Children with Cradle Cap: a Proof-of-Concept Pilot Study. AB - INTRODUCTION: Cradle cap is a very common condition in infants that presents as greasy, scaly patches on the scalp within the first weeks of life. Although usually disappearing by itself, the condition worries parents because of its appearance. When removing the scales, it is crucial to prevent spot bleedings to avoid infections. The investigational medical device LOYON((r)) (Cetiol((r)) CC, dimethicone) solution (G. Pohl-Boskamp GmbH & Co. KG, Hohenlockstedt, Germany) has the potential to meet these needs since it removes scales gently. It was, therefore, the aim of this proof-of-concept study to assess the efficacy and safety of topically applied, non-medicated LOYON((r)) in facilitating the removal of scaling in infants and children with cradle cap without inducing spot bleedings. METHODS: This single-center, open, proof-of-concept, pilot study was conducted in 20 male or female infants/children aged 3-36 months with clinically diagnosed cradle cap. The 8-day study period included one to three applications of LOYON((r)). Clinical assessment of scaling and secondary parameters was performed at baseline and after treatment. Adverse events were recorded. A questionnaire on subjective efficacy and usability was handed out to the parents. RESULTS: With a maximum of three applications of LOYON((r)) applied to 20 subjects, a reduction in scaling intensity from moderate or severe to very mild or mild was achieved in 80% of the subjects. Treatment success, defined as the reduction of the scaling baseline score by at least two points, was achieved in 50% of subjects. Results of this study do not indicate any safety concern. No spot bleedings were observed. LOYON((r)) was generally well tolerated and overall treatment was rated as "good" by the parents/legal guardians. CONCLUSION: This study suggests that LOYON((r)) is well tolerated, safe and effective in facilitating the removal of scaling in infants and children with cradle cap. With its gentle approach and rapid effect, LOYON((r)) thus represents a good alternative to home remedies for treatment of cradle cap. PMID- 25119139 TI - Analysis of the aggregation of an anionic porphyrin with a cationic surfactant at the supercritical carbon dioxide-water interface using UV-visible external reflection spectrometry. AB - An external reflection (ER) spectrometric device was developed to directly measure adsorbates at the supercritical carbon dioxide (SC-CO2)-water interface. The aggregation of diprotonated species of 5,10,15,20-tetraphenyl-21H,23H porphinetetrasulfonic acid (H4tpps(2-)) at the positively charged SC-CO2-water interface, prepared by adsorption by the cetyltrimethylammonium ion (CTA(+)), was studied using this device. Orientations of the H4tpps(2-) monomers and J aggregates at the SC-CO2-water interface were assessed using s- and p-polarized external reflection (ER) spectra. It appeared that the porphyrin plane of the H4tpps(2-) monomer was nearly parallel to the SC-CO2-water interface, and that the long axis of the rod-like H4tpps(2-) J-aggregate was also nearly parallel to the interface. Dependence of the ER spectra on CTA(+) concentration and CO2 pressure were investigated, and the interfacial CTA(+) concentration was found to cause changes in the interfacial H4tpps(2-) species present. Increasing the CO2 pressure changed the interfacial species from the H4tpps(2-) monomer to the H4tpps(2-) J-aggregate because the interfacial CTA(+) concentration increased as the pressure increased. This suggests that the interfacial chemical species can be changed by controlling the pressure and temperature of the SC-CO2. This is the first report of direct measurements of the chemical species at the SC-CO2-water interface, as far as we know. PMID- 25119140 TI - Characterization of the peer review network at the Center for Scientific Review, National Institutes of Health. AB - The National Institutes of Health (NIH) is the largest source of funding for biomedical research in the world. This funding is largely effected through a competitive grants process. Each year the Center for Scientific Review (CSR) at NIH manages the evaluation, by peer review, of more than 55,000 grant applications. A relevant management question is how this scientific evaluation system, supported by finite resources, could be continuously evaluated and improved for maximal benefit to the scientific community and the taxpaying public. Towards this purpose, we have created the first system-level description of peer review at CSR by applying text analysis, bibliometric, and graph visualization techniques to administrative records. We identify otherwise latent relationships across scientific clusters, which in turn suggest opportunities for structural reorganization of the system based on expert evaluation. Such studies support the creation of monitoring tools and provide transparency and knowledge to stakeholders. PMID- 25119138 TI - A comparative study of techniques for differential expression analysis on RNA-Seq data. AB - Recent advances in next-generation sequencing technology allow high-throughput cDNA sequencing (RNA-Seq) to be widely applied in transcriptomic studies, in particular for detecting differentially expressed genes between groups. Many software packages have been developed for the identification of differentially expressed genes (DEGs) between treatment groups based on RNA-Seq data. However, there is a lack of consensus on how to approach an optimal study design and choice of suitable software for the analysis. In this comparative study we evaluate the performance of three of the most frequently used software tools: Cufflinks-Cuffdiff2, DESeq and edgeR. A number of important parameters of RNA-Seq technology were taken into consideration, including the number of replicates, sequencing depth, and balanced vs. unbalanced sequencing depth within and between groups. We benchmarked results relative to sets of DEGs identified through either quantitative RT-PCR or microarray. We observed that edgeR performs slightly better than DESeq and Cuffdiff2 in terms of the ability to uncover true positives. Overall, DESeq or taking the intersection of DEGs from two or more tools is recommended if the number of false positives is a major concern in the study. In other circumstances, edgeR is slightly preferable for differential expression analysis at the expense of potentially introducing more false positives. PMID- 25119141 TI - Potassium-sulfur batteries: a new member of room-temperature rechargeable metal sulfur batteries. AB - We report room-temperature rechargeable potassium-sulfur (K-S) batteries using ordered mesoporous carbon (CMK-3)/sulfur and polyanilime (PANI) coated CMK 3/sulfur composites as the cathode and metallic potassium as the anode. The electrochemical reaction mechanism was investigated by electrochemical tests, TEM, XRD, and Raman spectra. It was found that K-S batteries delivered two reduction peaks located at about 2.1 and 1.8 V and one oxidation peak at about 2.2 V, respectively. Meanwhile, K2S3 was the major discharge product that could be charged to reversibly form S and K ion. Through optimization of sulfur content, the CMK-3/sulfur composite with 40.8 wt % S displayed an initial discharge capacity of 512.7 mAh g(-1) and a capacity of 202.3 mAh g(-1) after 50 cycles at a current density of 50 mA g(-1). A coating of conductive polyanilime (PANI) on the CMK-3/sulfur composite is effective in enhancing the cycling performance. In comparison, PANI@CMK-3/sulfur composite showed a capacity of 329.3 mAh g(-1) after 50 cycles at 50 mA g(-1). The results shed light on the basic study of rechargeable K-S batteries. PMID- 25119142 TI - Povarov-type reaction using methyl as new input: direct synthesis of substituted quinolines by I2-mediated formal [3 + 2 + 1] cycloaddition. AB - A highly efficient molecular iodine mediated formal [3 + 2 + 1] cycloaddition reaction for the direct synthesis of substituted quinolines from methyl ketones, arylamines, and styrenes is developed. The methyl group of the methyl ketone represents uniquely reactive input in the Povarov reaction. A self-sequenced iodination/Kornblum oxidation/Povarov/aromatization mechanism has been proposed as a possible reaction sequence to account for the results observed in this study. PMID- 25119143 TI - Multiscale modeling of the electrostatic impact of self-assembled monolayers used as gate dielectric treatment in organic thin-film transistors. AB - This study sheds light on the microscopic mechanisms by which self-assembled monolayers (SAMs) determine the onset voltage in organic thin-film transistors (OTFTs). Experiments and modeling are combined to investigate the self-assembly and electrostatic interaction processes in prototypical OTFT structures (SiO2/SAM/pentacene), where alkylated and fluoroalkylated silane SAMs are compared. The results highlight the coverage-dependent impact of the SAM on the density of semiconductor states and enable the rationalization and the control of the OTFT characteristics. PMID- 25119144 TI - Do the ends justify the means? A test of alternatives to the FDA proposed cigarette warning labels. AB - Three studies provide empirical, social scientific tests of alternatives to the originally proposed U.S. Food and Drug Administration (FDA) cigarette package warning labels on health risk beliefs, perceived fear, and effectiveness. Our research addresses questions at the root of the legal disputes surrounding FDA regulation of cigarette package warning labels. Specifically, we describe results from three studies that investigate the mediating role of health beliefs and perceived fear in shaping message effectiveness and intentions to quit. The first study featured nonsmoking young adults, while the second and third studies sampled adult daily smokers. Each study was a randomized experiment with five warning-label image conditions: full-color graphic warning labels, black-and white graphic warning labels, warning text (no graphic image), Surgeon General's warning labels, and no warning. Results consistently indicate that graphic warning labels (in both color and black-and-white) promote increased perceptions of fear, which in turn are associated with greater (perceived and actual) effectiveness. We conclude with a discussion of the results, highlighting implications, public policy considerations, and suggestions for future research. PMID- 25119145 TI - Disturbed cortico-amygdalar functional connectivity as pathophysiological correlate of working memory deficits in bipolar affective disorder. AB - Patients suffering from bipolar affective disorder show deficits in working memory functions. In a previous functional magnetic resonance imaging study, we observed an abnormal hyperactivity of the amygdala in bipolar patients during articulatory rehearsal in verbal working memory. In the present study, we investigated the dynamic neurofunctional interactions between the right amygdala and the brain systems that underlie verbal working memory in both bipolar patients and healthy controls. In total, 18 euthymic bipolar patients and 18 healthy controls performed a modified version of the Sternberg item-recognition (working memory) task. We used the psychophysiological interaction approach in order to assess functional connectivity between the right amygdala and the brain regions involved in verbal working memory. In healthy subjects, we found significant negative functional interactions between the right amygdala and multiple cortical brain areas involved in verbal working memory. In comparison with the healthy control subjects, bipolar patients exhibited significantly reduced functional interactions of the right amygdala particularly with the right hemispheric, i.e., ipsilateral, cortical regions supporting verbal working memory. Together with our previous finding of amygdala hyperactivity in bipolar patients during verbal rehearsal, the present results suggest that a disturbed right-hemispheric "cognitive-emotional" interaction between the amygdala and cortical brain regions underlying working memory may be responsible for amygdala hyperactivation and affects verbal working memory (deficits) in bipolar patients. PMID- 25119148 TI - Darzens reaction rate enhancement using aqueous media leading to a high level of kinetically controlled diastereoselective synthesis of steroidal epoxyketones. AB - Darzens reactions between halocarbonyls and aldehydes have been carried out in water in the presence of a Li(+)-containing base, a phase-transfer catalyst, and granular polytetrafluoroethylene under mechanical stirring. Reactions using both aromatic and aliphatic aldehydes produced epoxides stereoselectively in good to excellent yields. This is the first time that aliphatic aldehydes with alpha-H have been used in aqueous Darzens reactions. The Darzens reactions were much faster in water than in organic solvents. This aqueous rate enhancement occurred for Darzens reactions between enantiopure steroidal haloketones and aldehydes, yielding enantiopure spiroepoxides with a high level of kinetically controlled diastereoselectivity. Chromatography was avoided in the purifications of the steroidal spiroepoxides. This is an example of preparing enantiopure epoxyketones via aqueous Darzens reaction using chiral alpha-haloketone substrates. PMID- 25119147 TI - Development and evaluation of magnetic microemulsion: tool for targeted delivery of camptothecin to BALB/c mice-bearing breast cancer. AB - PURPOSE: Development and evaluation of camptothecin-loaded-microemulsion (ME) and -magnetic microemulsion (MME) for passive/active-targeted delivery to BALB/c mice bearing breast cancer. METHODS: Based on the pseudo-ternary phase diagrams camptothecin-loaded-MEs and -MMEs were developed using benzyl alcohol:Captex 300 (3:1), TPGS:Tween 80 (2:1) and water. Furthermore, characterized for their droplet size distribution, magnetic susceptibility and effect of droplet size in plasma and evaluated for in vitro and in vivo targeting potential, drug release, haemolytic potential, cytotoxicity, genotoxicity, in vivo biodistribution and lactone ring stability. RESULTS: Drug-loaded MEs showed uniform droplet distribution, extended drug release (76.07 +/- 4.30% at 24 h), acceptable level of haemolytic activity (<20%), significant cytotoxicity (129 +/- 3.9 ng/mL) against MCF-7 cancer cells and low DNA damage in lymphocytes. Targeting potential of MMEs was documented in 4T1 breast cancer-induced BALB/c mice. MMEs were concentrated more at the target tissue on introduction of external magnetic field. In vivo biodistribution study documented the active targeting of 5067.56 +/- 354.72 ng/gm and passive targeting of 1677.58 +/- 134.20 ng/gm camptothecin to breast cancer from MME and ME, respectively. Lactone stability study shows around 80% of the lactone stable at 24 h. CONCLUSIONS: Developed ME and MME may act as a promising nanocarrier for efficient targeting of breast cancer tissues. PMID- 25119146 TI - DSM-5 reviewed from different angles: goal attainment, rationality, use of evidence, consequences--part 1: general aspects and paradigmatic discussion of depressive disorders. AB - DSM-5 was published in 2013 after about 10 years of preparation. Part 1 of this paper discusses several more general aspects of DSM-5 and offers a detailed, paradigmatic analysis of changes made to the chapter on depressive disorders. The background for the changes is analysed on the basis of a PubMed search and review papers on the classification of mental disorders in general and on empirical knowledge about individual disorders. Contrary to the original plans, DSM-5 has not introduced a primarily dimensional diagnostic system but has widely preserved the categorical system of disorders. Also, it has not adopted a more neurobiological approach to disorders by including biological markers to increase the objectivity of psychiatric diagnoses but has maintained the primarily symptom based, descriptive approach. The criteria for some disorders have been changed, including affective, schizophrenic and addiction disorders, and a few new disorders have been added. A minimal version of the dimensional approach was realised through the introduction of several transnosological specifiers and the option to make symptom- or syndrome-related severity and dimensional assessments. These specifiers and assessments might allow a more individualised description of a patient's psychopathological state and more personalised treatment. However, most of the symptom- and syndrome-related assessments are not mandatory and therefore may not be used in clinical practice. PMID- 25119149 TI - Controlled stripes of ultrafine ferroelectric domains. AB - In the pursuit of ferroic-based (nano)electronics, it is essential to minutely control domain patterns and domain switching. The ability to control domain width, orientation and position is a prerequisite for circuitry based on fine domains. Here, we develop the underlying theory towards growth of ultra-fine domain patterns, substantiate the theory by numerical modelling of practical situations and implement the gained understanding using the most widely applied ferroelectric, Pb(Zr,Ti)O3, demonstrating controlled stripes of 10 nm wide domains that extend in one direction along tens of micrometres. The observed electrical conductivity along these thin domains embedded in the otherwise insulating film confirms their potential for electronic applications. PMID- 25119151 TI - Bani Adam: Saadi Shirazi (AD 1184-1283/1291) and the concept of empathy. PMID- 25119150 TI - Temporal and spatial distribution of the aquaporin 1 in spinal cord and dorsal root ganglia after traumatic injuries of the sciatic nerve. AB - PURPOSE: The aquaporin family comprises a large family of integral membrane proteins that enable the movement of water and other small, neutral solutes across plasma membranes. Although function and mechanism of aquaporins in central nervous system injury have been reported, the pathophysiologic role of aquaporin 1 (AQP1) in peripheral nerve has not been extensively documented. In the present study, we aimed to study the temporal and spatial distribution of AQP1 in spinal cord and dorsal root ganglia after sciatic nerve injury. METHODS: Forty-eight adult female mice were randomly divided into four groups (intact controls, sham operated, cut injury, and crush injury). Animals receiving cut or crush injuries were sacrificed at the 2nd, 24th, and 48th postoperative hours. Spinal cord samples at the level of lumbosacral intumescences and corresponding dorsal root ganglia on the experimental and contralateral side were dissected free and proceeded to AQP1 immunohistochemistry. RESULTS: Our quantitative estimations revealed that a sharp increase in AQP1 immunoreactivity at the 24th postoperative hour was observed. This sharp increase was no more evident at 48 h after sciatic nerve injury. Identical peak was observed after both cut and crush injuries. CONCLUSIONS: We demonstrated that there was a temporal relationship with an increased expression of AQP1 following injury sustained to the sciatic nerve that was significantly observed in dorsal root ganglia and spinal cord. Those expressions were also subsided over time. PMID- 25119152 TI - A hybrid technique for ventriculoatrial shunt implantation--technical note. AB - PURPOSE: The aim of the article is to present the new hybrid technique for ventriculoatrial shunt implantation. METHODS: Two-and-a-half-year-old boy needed ventriculoatrial shunt implantation due to communicating hydrocephalus and impaired absorptive ability of the peritoneum. Because of a complete occlusion of the right internal jugular vein and critical stenosis of a distal part of the left internal jugular vein, the procedure was performed under fluoroscopy guidance in the catheterisation laboratory equipped with a 3-dimensional single plane angiography machine (Philips Allura--The Netherlands). At the level of critical stenosis of the left jugular vein, it was decided to perform a percutaneous venous balloon angioplasty. This procedure allowed inserting the ventriculoatrial shunt into the right atrium. RESULTS: The whole postoperative period was uneventful. Now, the child is free from symptoms of increased intracranial pressure. The boy has been followed for 9 months. In the control MRI examination, the ventricular system did not change as compared with the previous study. CONCLUSION: The disadvantage of the hemodynamic technique is a higher dose of X-ray irradiation in comparison to other techniques. The hybrid technique should be reserved only to very complicated cases. PMID- 25119154 TI - The importance of radiation worker studies. PMID- 25119153 TI - Neurocutaneous melanosis is associated with tethered spinal cord. AB - PURPOSE: Neurocutaneous melanosis (NCM) is a rare congenital disorder occurring in children born with multiple or large congenital melanocytic nevi (CMN) in association with melanocytic deposits in the leptomeninges. Multiple associations between NCM and other syndromes or neurologic abnormalities have been reported. Of note, there exists a possible association between NCM and tethered cord (TC). METHODS: We retrospectively reviewed charts and films of all patients with the diagnosis of NCM at the Children's Hospital of Pittsburgh (CHP) from August 2002 to present. RESULTS: Five children met the criteria for NCM at our institution over a 12-year period. Apart from the melanocytic deposits, one or more additional spinal abnormalities were identified in all children. Three children had radiographic evidence of a low-lying conus medullaris, two of which also demonstrated lipomatous infiltration of the filum terminale, consistent with a tethered cord (TC). CONCLUSIONS: Clinical features of NCM include dermatologic and neurologic manifestations. To date, this is the first series to note an association between NCM and TC. While nearly all recent series of NCM patients advocate early MRI of the neuroaxis, we recommend screening imaging of the spine on children with possible NCM regardless of the locations of CMN. PMID- 25119156 TI - Reference selection influences the reliability of conclusions. PMID- 25119158 TI - Magnetic resonance imaging in acute hamstring injury: can we provide a return to play prognosis? AB - BACKGROUND: Sports physicians are increasingly requested to perform magnetic resonance imaging (MRI) of acute hamstring muscle injuries and to provide a prognosis of the time to return to play (RTP) on the basis of their findings. OBJECTIVES: To systematically review the literature on the prognostic value of MRI findings for time to RTP in acute hamstring muscle injuries. DATA SOURCES: The databases of PubMed, EMBASE, CINAHL, Web of Science and Cochrane Library were searched in June 2013. STUDY ELIGIBILITY CRITERIA: Studies evaluating MRI as a prognostic tool for determining time to RTP in athletes with acute hamstring injuries were eligible for inclusion. DATA ANALYSIS: Two authors independently screened the search results and assessed risk of bias using criteria for quality appraisal of prognosis studies. A best-evidence synthesis was used to identify the level of evidence. RESULTS: Of the 12 studies included, one had a low risk of bias and 11 a high risk of bias. There is moderate evidence that injuries without hyperintensity on fluid-sensitive sequences are associated with a shorter time to RTP and that injuries involving the proximal free tendon are associated with a longer time to RTP. Limited evidence was found for an association of central tendon disruption, injury not affecting the musculotendinous junction and a total rupture with a longer time to RTP. The other MRI findings studied showed either no association or there was conflicting evidence. CONCLUSION: There is currently no strong evidence for any MRI finding that gives a prognosis on the time to RTP after an acute hamstring injury, owing to considerable risks of bias in the studies on this topic. PMID- 25119157 TI - Cooling athletes with a spinal cord injury. AB - Cooling strategies that help prevent a reduction in exercise capacity whilst exercising in the heat have received considerable research interest over the past 3 decades, especially in the lead up to a relatively hot Olympic and Paralympic Games. Progressing into the next Olympic/Paralympic cycle, the host, Rio de Janeiro, could again present an environmental challenge for competing athletes. Despite the interest and vast array of research into cooling strategies for the able-bodied athlete, less is known regarding the application of these cooling strategies in the thermoregulatory impaired spinal cord injured (SCI) athletic population. Individuals with a spinal cord injury (SCI) have a reduced afferent input to the thermoregulatory centre and a loss of both sweating capacity and vasomotor control below the level of the spinal cord lesion. The magnitude of this thermoregulatory impairment is proportional to the level of the lesion. For instance, individuals with high-level lesions (tetraplegia) are at a greater risk of heat illness than individuals with lower-level lesions (paraplegia) at a given exercise intensity. Therefore, cooling strategies may be highly beneficial in this population group, even in moderate ambient conditions (~21 degrees C). This review was undertaken to examine the scientific literature that addresses the application of cooling strategies in individuals with an SCI. Each method is discussed in regards to the practical issues associated with the method and the potential underlying mechanism. For instance, site-specific cooling would be more suitable for an athlete with an SCI than whole body water immersion, due to the practical difficulties of administering this method in this population group. From the studies reviewed, wearing an ice vest during intermittent sprint exercise has been shown to decrease thermal strain and improve performance. These garments have also been shown to be effective during exercise in the able-bodied. Drawing on additional findings from the able-bodied literature, the combination of methods used prior to and during exercise and/or during rest periods/half-time may increase the effectiveness of a strategy. However, due to the paucity of research involving athletes with an SCI, it is difficult to establish an optimal cooling strategy. Future studies are needed to ensure that research outcomes can be translated into meaningful performance enhancements by investigating cooling strategies under the constraints of actual competition. Cooling strategies that meet the demands of intermittent wheelchair sports need to be identified, with particular attention to the logistics of the sport. PMID- 25119159 TI - Effect of (a)synchronous light fluctuation on diversity, functional and structural stability of a marine phytoplankton metacommunity. AB - Disentangling the mechanisms that maintain the stability of communities and ecosystem properties has become a major research focus in ecology in the face of anthropogenic environmental change. Dispersal plays a pivotal role in maintaining diversity in spatially subdivided communities, but only a few experiments have simultaneously investigated how dispersal and environmental fluctuation affect community dynamics and ecosystem stability. We performed an experimental study using marine phytoplankton species as model organisms to test these mechanisms in a metacommunity context. We established three levels of dispersal and exposed the phytoplankton to fluctuating light levels, where fluctuations were either spatially asynchronous or synchronous across patches of the metacommunity. Dispersal had no effect on diversity and ecosystem function (biomass), while light fluctuations affected both evenness and community biomass. The temporal variability of community biomass was reduced by fluctuating light and temporal beta diversity was influenced interactively by dispersal and fluctuation, whereas spatial variability in community biomass and beta diversity were barely affected by treatments. Along the establishing gradient of species richness and dominance, community biomass increased but temporal variability of biomass decreased, thus highest stability was associated with species-rich but highly uneven communities and less influenced by compensatory dynamics. In conclusion, both specific traits (dominance) and diversity (richness) affected the stability of metacommunities under fluctuating conditions. PMID- 25119155 TI - Physical activity, air pollution and the brain. AB - This review introduces an emerging research field that is focused on studying the effect of exposure to air pollution during exercise on cognition, with specific attention to the impact on concentrations of brain-derived neurotrophic factor (BDNF) and inflammatory markers. It has been repeatedly demonstrated that regular physical activity enhances cognition, and evidence suggests that BDNF, a neurotrophin, plays a key role in the mechanism. Today, however, air pollution is an environmental problem worldwide and the high traffic density, especially in urban environments and cities, is a major cause of this problem. During exercise, the intake of air pollution increases considerably due to an increased ventilation rate and particle deposition fraction. Recently, air pollution exposure has been linked to adverse effects on the brain such as cognitive decline and neuropathology. Inflammation and oxidative stress seem to play an important role in inducing these health effects. We believe that there is a need to investigate whether the well-known benefits of regular physical activity on the brain also apply when physical activity is performed in polluted air. We also report our findings about exercising in an environment with ambient levels of air pollutants. Based on the latter results, we hypothesize that traffic-related air pollution exposure during exercise may inhibit the positive effect of exercise on cognition. PMID- 25119161 TI - Production of arachidonic and eicosapentaenoic acids by the marine oomycete Halophytophthora. AB - Polyunsaturated fatty acids (PUFAs) are fatty acids with more than one double bond in the chemical structure. Arachidonic acid (ARA, 20:4 (n-6)) and eicosapentaenoic acid (EPA, 22:5 (n-3)) are common PUFAs with beneficial health effects. Marine fish and meat are the main sources of omega-3 and omega-6 fatty acids in human's diet, respectively. In particular, there is a general decline in fish catch, implicating the need for an alternative source of omega-3 fatty acids. Previous studies have examined the production of polyunsaturated fatty acids including ARA and EPA by various microorganisms, including microalgae, fungi, and thraustochytrids. In this study, the production of ARA and EPA by 10 isolates of four estuarine Halophytophthora species (Halophytophthora avicenniae, Halophytophthora polymorphica, Halophytophthora vesicula, and Halophytophthora spinosa var. spinosa) cultured from fallen mangrove leaves in Taiwan was examined. The yield of ARA ranged from 0.004 to 0.052 g/L with the highest yield of ARA obtained from H. spinosa var. spinosa IMB162, but no or a very low level of EPA was produced by IMB162. For EPA production by Halophytophthora spp., the yield ranged from 0 to 0.047 g/L. Percentage of ARA in total fatty acid ranged between 7.16 and 25.02%. One-way ANOVA analysis using Tukey Test (p >= 0.05) suggested that there is significant difference in the percentage of EPA in total fatty acid produced by the isolates, which ranged from 0.01 to 18.42%. BODIPY 505/515 fluorescent staining suggests that lipid bodies were evenly distributed in the mycelia of Halophytophthora species. PMID- 25119160 TI - A tree-ring perspective on the terrestrial carbon cycle. AB - Tree-ring records can provide valuable information to advance our understanding of contemporary terrestrial carbon cycling and to reconstruct key metrics in the decades preceding monitoring data. The growing use of tree rings in carbon-cycle research is being facilitated by increasing recognition of reciprocal benefits among research communities. Yet, basic questions persist regarding what tree rings represent at the ecosystem level, how to optimally integrate them with other data streams, and what related challenges need to be overcome. It is also apparent that considerable unexplored potential exists for tree rings to refine assessments of terrestrial carbon cycling across a range of temporal and spatial domains. Here, we summarize recent advances and highlight promising paths of investigation with respect to (1) growth phenology, (2) forest productivity trends and variability, (3) CO2 fertilization and water-use efficiency, (4) forest disturbances, and (5) comparisons between observational and computational forest productivity estimates. We encourage the integration of tree-ring data: with eddy-covariance measurements to investigate carbon allocation patterns and water-use efficiency; with remotely sensed observations to distinguish the timing of cambial growth and leaf phenology; and with forest inventories to develop continuous, annually-resolved and long-term carbon budgets. In addition, we note the potential of tree-ring records and derivatives thereof to help evaluate the performance of earth system models regarding the simulated magnitude and dynamics of forest carbon uptake, and inform these models about growth responses to (non )climatic drivers. Such efforts are expected to improve our understanding of forest carbon cycling and place current developments into a long-term perspective. PMID- 25119162 TI - Predicted effects of gypsy moth defoliation and climate change on forest carbon dynamics in the New Jersey pine barrens. AB - Disturbance regimes within temperate forests can significantly impact carbon cycling. Additionally, projected climate change in combination with multiple, interacting disturbance effects may disrupt the capacity of forests to act as carbon sinks at large spatial and temporal scales. We used a spatially explicit forest succession and disturbance model, LANDIS-II, to model the effects of climate change, gypsy moth (Lymantria dispar L.) defoliation, and wildfire on the C dynamics of the forests of the New Jersey Pine Barrens over the next century. Climate scenarios were simulated using current climate conditions (baseline), as well as a high emissions scenario (HadCM3 A2 emissions scenario). Our results suggest that long-term changes in C cycling will be driven more by climate change than by fire or gypsy moths over the next century. We also found that simulated disturbances will affect species composition more than tree growth or C sequestration rates at the landscape level. Projected changes in tree species biomass indicate a potential increase in oaks with climate change and gypsy moth defoliation over the course of the 100-year simulation, exacerbating current successional trends towards increased oak abundance. Our research suggests that defoliation under climate change may play a critical role in increasing the variability of tree growth rates and in determining landscape species composition over the next 100 years. PMID- 25119163 TI - Reduction in the size of enlarged pelvic lymph nodes after chemoradiation therapy is associated with fewer lymph node metastases in locally advanced rectal carcinoma. AB - PURPOSE: We hypothesized that a reduction in the size of the lymph nodes after neoadjuvant therapy for locally advanced rectal carcinoma would be associated with decreased lymph node metastases and/or a better prognosis. METHODS: Between March 2006 and April 2012, 71 patients with primary rectal cancer received neoadjuvant chemoradiation therapy (CRT). For all lymph nodes 5 mm or larger in size, the major and minor axes were measured on CT scan images, and the product was calculated. The lymph node size was determined before and after CRT. The patients were divided into three groups based on the lymph node size before and after treatment. Group A exhibited a reduction in size of 60% or more, Group B a reduction of less than 60% and Group C had no lymph node enlargement before treatment. RESULTS: The incidence of lymph node metastases on pathological examination was 15% in Group A and 50% in Group B (p = 0.006). The five-year disease-free survival in Group A was 84% compared with 78% in Group B (log rank p = 0.34). The five-year overall survival in Group A was 92% compared with 74% in Group B (log rank p = 0.088). CONCLUSIONS: A reduction in the size of enlarged lymph nodes after neoadjuvant therapy may be a useful prognostic factor for recurrence and survival. PMID- 25119167 TI - In memoriam Professor Przemyslaw Gabryel (01.12.1919 - 27.04.2014). PMID- 25119165 TI - Brain-derived neurotrophic factor and interleukin-6 levels in the serum and cerebrospinal fluid of children with viral infection-induced encephalopathy. AB - We investigated changes in the brain-derived neurotrophic factor (BDNF) and interleukin (IL)-6 levels in pediatric patients with central nervous system (CNS) infections, particularly viral infection-induced encephalopathy. Over a 5-year study period, 24 children hospitalized with encephalopathy were grouped based on their acute encephalopathy type (the excitotoxicity, cytokine storm, and metabolic error types). Children without CNS infections served as controls. In serum and cerebrospinal fluid (CSF) samples, BDNF and IL-6 levels were increased in all encephalopathy groups, and significant increases were noted in the influenza-associated and cytokine storm encephalopathy groups. Children with sequelae showed higher BDNF and IL-6 levels than those without sequelae. In pediatric patients, changes in serum and CSF BDNF and IL-6 levels may serve as a prognostic index of CNS infections, particularly for the diagnosis of encephalopathy and differentiation of encephalopathy types. PMID- 25119164 TI - The beneficial effect of chitooligosaccharides on cell behavior and function of primary Schwann cells is accompanied by up-regulation of adhesion proteins and neurotrophins. AB - Chitosan-based tissue engineered nerve grafts are successfully used for bridging peripheral nerve gaps. The biodegradation products of chitosan are water dissolvable chitooligosaccharides (COSs), which have been shown to support peripheral nerve regeneration. In this study, we aimed to examine in vitro interactions between COSs and Schwann cells (SCs), the principal glial cells in the peripheral nervous system. Treatment of primary SCs with COSs enhanced cell survival and promoted cell proliferation in a dose-dependent manner (0.25-1.0 mg/ml), as determined by real-time cell analyzer-based assay, cell growth assay, cell cycle analysis, and EdU incorporation. Western blot analysis and immunocytochemistry with antibodies against MBP and MAG (two myelin-specific markers) showed that COSs enhanced axonal myelination in a co-culture system consisting of SCs and dorsal root ganglia (DRGs). Furthermore, we observed that COSs enhanced the protein expression of N-cadherin and beta-catenin in primary SCs, and also increased the release of BDNF and NGF in co-culture of SCs with DRGs. And we also noted that knockdown of N-cadherin in primary SCs reduced COSs induced increase in cell proliferation. Our findings suggested that beneficial effects of COSs on cell behavior and functions of primary SCs might be accompanied by up-regulation of adhesion proteins and neurotrophins, thus providing a new insight into the supportive role of COSs during peripheral nerve regeneration. PMID- 25119168 TI - Review of renal tumors associated with Birt-Hogg-Dube syndrome with focus on clinical and pathobiological aspects. AB - Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant inherited disorder characterized by clinical features of skin lesions, pulmonary lesions and renal tumor. The gene responsible for this syndrome is located on chromosome 17p11.2 and designated as FLCN. In this article, we review renal tumors associated with BHDS with a focus on clinical and pathobiological aspects. Renal tumors often occur multifocally or bilaterally in the imaging analyses or gross examination. Histological examination of renal tumors includes a variety of subtypes such as hybrid oncocytic tumor, chromophobe renal cell carcinoma (RCC), oncocytoma, clear cell RCC and papillary RCC. The histologic discordance in multiple tumors seems to be characteristic of this syndrome. Oncocytosis is observed histologically in about half of the cases. Several investigations have elucidated that folliculin may be involved in the mammalian target of rapamycin (mTOR) pathway recently. Renal tumors composed of clear cells may behave in an aggressive fashion. However, renal tumors including hybrid oncocytic tumor, chromophobe RCC and oncocytoma behave mostly in an indolent fashion. PMID- 25119169 TI - Ductal adenocarcinoma of the pancreas usually retained SMAD4 and p53 protein status as well as expression of epithelial-to-mesenchymal transition markers and cell cycle regulators at the stage of liver metastasis. AB - There are limited data on the biology of metastatic pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to compare the expression of immunohistochemical markers that may be involved in the development of metastatic disease in primary PDAC and in synchronous liver metastatic tissues. Thirty-two stains (corresponding to proteins encoded by 31 genes: SMAD4, TP53, ACTA2, CDH1, CDKN1A, CLDN1, CLDN4, CLDN7, CTNNB1, EGFR, ERBB2, FN1, KRT19, MAPK1/MAPK3, MAPK14, MKI67, MMP2, MMP9, MUC1 (3 antibodies), MUC5AC, MUC6, MTOR, MYC, NES, PTGS2, RPS6, RPS6KB1, TGFB1, TGFBR1, VIM) were evaluated using tissue microarray of 26 pairs of primary PDACs and their liver metastases. There were no significant differences in expression levels of examined proteins between primary and secondary lesions. In particular, metastatic PDAC retained the primary tumour's SMAD4 protein status in all and p53 protein status in all but one case. This surprising homogeneity also involved expression levels of markers of epithelial-to-mesenchymal transition as well as cell cycle regulators studied. In conclusion, the biological profiles of primary PDACs and their liver metastases seemed to be similar. Molecular alterations of PDAC related to a set of immunohistochemical markers examined in the present study were already present at the stage of localized disease. PMID- 25119170 TI - Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2. AB - Renal clear cell carcinoma (CCRCC) is an aggressive tumor for which new prognostic factors are needed. It has been suggested that CCRCCs co-expressing P53 and MDM2 could represent a special subgroup; therefore the aim of this study was to explore their immunohistochemical features. The material studied consisted of 470 cases of CCRCC. Immunohistochemistry for MDM2, P53, Ki-67, VEGF-A, VEGF-C, VEGF-D, GLUT1, CA9, and CK 7 was performed on tissue microarrays and assessed semi-quantitatively. On average, 6.6% or 5.3% of cases were P53+/MDM2+, depending on the P53 antibody used. The mean percentage of Ki-67 positive cells was 0.6% and p53-positive MDM2-positive cases showed significantly higher expression of Ki 67. The other immunohistochemical parameters studied did not differ between p53 positive MDM2-positive cases and the rest of the subtypes studied. Expression of almost all immunohistochemical markers differed with respect to pT stage; only for CA9 was the difference not significant. Furthermore, almost all immunohistochemical markers studied differed with respect to differences in grade; only for GLUT1 was the difference not significant. Our results suggest that with the exception of Ki-67, there are no significant associations between analyzed markers and the double P53+/MDM2+ phenotype. PMID- 25119171 TI - Histochemical and immunohistochemical characteristics of elastofibromas. AB - Elastofibromas are slow-growing and rare soft-tissue tumors. The etiology and pathogenetic mechanisms are still controversial and there are only a few studies in the literature investigating the histochemical, immunohistochemical, and genetic features to determine the pathogenesis. We investigated the cellular composition of lesions with a diagnosis of elastofibroma in 17 patients by using histochemical and immunohistochemical methods. There were 17 cases with a mean age of 53.5 years. Mean lesion diameter was 6.6 cm. The immunohistochemical method showed vimentin and factor XIIIa positivity in all cases. Four cases had focal myoglobin positivity in the spindle-shaped cells between the collagen fibers. Spindle cells were positive for CD34 in 8 cases. Smooth muscle actin, desmin, type 4 collagen and laminin were negative in all cases. The elastic nature of the abnormal fibers was shown histoch with Verhoeff elastin staining and aldehyde fuchsin staining in all cases. Our results have shown that the concurrent positivity of factor XIIIa and CD34 in the cells forming the lesion might show that the lesionoriginates from primitive dermal mesenchymal cells. In addition, the myoglobin positivity found in some cases indicates the possibility of a myofibroblastic origin of elastofibromas. PMID- 25119172 TI - The influence of Th1/Th2 and CD4+ regulatory t cells of mesenteric lymph nodes on systemic lipopolysaccharide. AB - Our aims were to study the influence of the mesenteric lymph nodes (MLN) of rats on systemic lipopolysaccharide and to identify the factor that affects the intestinal endotoxin translocation. Ninety-six male Wistar rats were randomly divided into a sham-operation group (S group) and a cecal ligation and perforation group (CLP group). Twenty-four hours after modeling, we tested the Th1/Th2 ratio and percentage of CD4+CD25+Foxp3+ Treg in the MLN. At the same time, the lipopolysaccharide (LPS) in the abdominal aortic blood was detected. In the CLP group, the Th1/Th2 ratio was obviously lower than in the S group. Otherwise, the percentage of CD4+CD25+Foxp3+ Treg of the CLP group was significantly higher than the S group. In the abdominal aortic blood, the LPS level of the CLP group was also higher than in the S group. Through correlation analysis, we found that the level of LPS was positively correlated with the percentage of CD4+CD25+Foxp3+ Treg, and negatively correlated with the Th1/Th2 ratio. This model reveals that the immune suppression of the MLN might affect the level of LPS in the abdominal aortic blood, which might play a certain role in affecting the endotoxin translocation. PMID- 25119173 TI - Parotid gland tumors in children - pre- and postoperative diagnostic difficulties. AB - Major salivary gland tumors are very rare in the developmental period. Confirming tumor changes in the salivary gland requires precise diagnostic imaging involving an ultrasonography scan, computed tomography and magnetic resonance. Needle aspiration biopsy (NAB) of the tumor is of high importance. Excision is the basic treatment method in cases of parotid gland tumor. The statistical data concerning tumors favor less invasive methods, which seems logical in the population of children. The surgical methods used in tumor treatment feature extracapsular excision of tumor, partial parotidectomy and total parotidectomy, sometimes followed by lymphatic node surgery. The clinical cases presented in the paper show difficulties with pre- and postoperative histopathological diagnosis in major salivary gland tumors in children. A core biopsy of the tumor may improve the accuracy of preoperative diagnosis but it does not exclude the possibility of misdiagnosis. PMID- 25119174 TI - Expression of insulin-like growth factor receptor type 1 correlate with lymphatic metastases in human gastric cancer. AB - Most patients with gastric cancer are diagnosed at advanced clinical stages with a high frequency of lymph node metastasis. It is very important to find novel factors for the early diagnostic and prognostic evaluation of gastric cancer. It has been shown that IGF-1R activates mitotic division and inhibits apoptosis of cancer cells through the activation of signaling MAP/ERK and PI3K/Akt-1 pathways. IGF-1R plays a role in cell transformation and maintenance of the phenotype in modified cells. Moreover, an IGF-1 receptor effect influences the processes of adhesion, migration, invasion and metastasis of tumor cells. The aim of the study was to assess the expression of IGF-1R in gastric carcinoma in correlation with selected anatomo-clinical parameters. The study enrolled a group of 49 patients treated surgically for gastric cancer. 28 patients had no lymph node metastases. The expression of the studied proteins was assessed using the immunohistochemical method. We found that the expression of IGF-1R in gastric cancer is associated with lymph node metastasis (p < 0.001), is correlated with worse prognosis and high histological malignancy grade, and is an independent predictor of survival in patients with gastric cancer (p < 0.001). IGF-1R may play an important role in tumor growth and metastasis via the lymphatic pathway. PMID- 25119175 TI - Polymorphism of the glutathione S-transferase P1 gene (GST-pi) in breast carcinoma. AB - Breast carcinoma is the most common cancer and cause of death among females worldwide, including Jordan. The risk factors for breast carcinoma are linked to DNA mutation and failure of DNA repair or detoxification systems. Identification of susceptibility factors that predispose individuals to breast carcinoma if they are exposed to particular environmental agents might give further insight into the etiology of this malignancy. The glutathione S-transferase (GST) enzyme family detoxifies carcinogenic compounds. Several genes that code for these enzymes are polymorphic, with particular genotypes previously shown to confer an increased carcinoma risk. The present study investigates GST-pi polymorphism in 100-tissue samples previously diagnosed as breast carcinoma, and in 48 non-cancer age-matched breast tissues, using the restriction fragment length polymorphism (RFLP) method for the polymerase chain reaction (PCR) product. Among breast cancer cases, 58%, 40% and 2% were homozygous (Ile/Ile), heterozygous (Ile/Val) and homozygous (Val/Val) respectively. In the control group, 58%, 37.5% and 4.2% were homozygous (Ile/Ile), heterozygous (Ile/Val), and homozygous (Val/Val) respectively. Our results did not support the involvement of GST-pi gene polymorphism in susceptibility to breast carcinoma in the tested North Jordanian female population. PMID- 25119176 TI - Mast cell phenotype in benign and malignant tumors of the prostate. AB - The molecular phenotypic heterogeneity of mast cells (MCs) makes them attractive as potential therapeutic targets in anti-cancer adjuvant therapy. Mast cell aggregations observed in tumors suggested their involvement in tumor pathogenesis. Despite several studies using mast cell tryptase, MCs' involvement in the progression of prostate tumors has not been demonstrated. The aim of our study was to identify and quantify the phenotypic heterogeneity of MCs in prostate lesions. Our study included 7 cases of normal prostate, 25 cases of benign epithelial hyperplasia and 64 cases of prostate carcinoma. MCs were immunohistochemically assessed using three markers: tryptase, chymase and CD117. Two immunophenotypes of MCs were identified in benign lesions: tryptase+/CD117+/chymase- and tryptase-/chymase+/CD117+, located in peritumoral areas. Intratumoral MC phenotype of malignant lesions was characterized by tryptase+/chymase+/CD117+, while in the peritumoral areas three different MCs phenotypes were identified: tryptase+/chymase+/CD117-, tryptase+/CD117+/chymase- and chymase+/CD117+/tryptase-. Our results suggest the correlation of chymase positive MCs of the peritumoral areas and CD117 positive MCs of the intratumoral areas with tumor grade. PMID- 25119177 TI - Bilateral Sertoli cell adenoma in gonads, associated with serous cystadenoma. AB - Complete androgen insensitivity syndrome is an extremely infrequent disease. The patients exhibit female phenotype because of insensitivity to the androgen receptor and may develop tumors, especially in their undescended gonads. We report a case of bilateral Sertoli cell adenoma in gonads with unilateral serous cystadenoma, in an elderly phenotypic woman with primary amenorrhea. We also provide radiological and pathological studies. PMID- 25119178 TI - Renal myxoma: an unexpected differential diagnosis. AB - Myxomas are rare mesenchymal tumors that can appear in many anatomical locations, although they are mainly seen in heart and skin. To date, only twelve cases of pure renal myxomas have been reported in the literature. We describe a case of a young Cuban woman with an asymptomatic irregular cyst lesion in her left kidney which was eventually diagnosed as renal myxoma. We also provide radiological and pathological studies. PMID- 25119179 TI - Re: co-existence of intramuscular spindle cell lipoma with an intramuscular ordinary lipoma. Report of a case. PMID- 25119180 TI - Melanotic oncocytic metaplasia of the nasopharynx. AB - We report a rare case of melanotic oncocytic metaplasia of the nasopharynx in a 63-year-old man, presenting as several black nodules up to several millimeters at the nasopharynx. It is a benign mimicker of malignant melanoma. PMID- 25119181 TI - A prospective study of biomarker-guided chemotherapy in patients with non-small cell lung cancer. AB - PURPOSE: To assess the therapeutic value of biomarker-guided chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Eighty-five NSCLC patients at stage IIIb or IV were divided into two groups based on the feasibility of biomarker analysis. Group A included patients with biomarker data (n = 41); Group B were patients without biomarker results (n = 44). Tumor samples obtained by fiberoptic bronchoscopy and computerized tomography-guided needle biopsy were analyzed by immunohistochemistry for intratumoral level of excision repair cross-complementing gene 1 (ERCC1), ribonucleotide reductase M1 (RRM1), and beta-tubulin III. Chemotherapy regimens in Group A were determined according to the status of molecular signatures, whereas a standard gemcitabine plus cisplatin regimen was used for Group B. Tumor response, patient survival, and adverse effects were monitored for both groups. RESULTS: The overall response rate, defined as complete response plus partial response, was 56.1% for Group A, significantly higher than that in Group B (31.8%; P = 0.024). The median progression-free survival (PFS) time was 5.2 months for Group A, significantly longer than that of Group B (4.1 months; P = 0.026). The 1-year survival rate of Group A was 65.9%, significantly higher than that of Group B (40.9%; P = 0.021), whereas the median overall survival times were 13.5 versus 12.5 months for Groups A and B, respectively (P = 0.483). The adverse effects in the two groups were essentially the same. CONCLUSIONS: Biomarker-tailored chemotherapy based on ERCC1, RRM1, and beta-tubulin III expression showed significantly increased response rate, median PFS time, and 1-year survival rate in patients with NSCLC. PMID- 25119183 TI - The combination of Cl-IB-MECA with paclitaxel: a new anti-metastatic therapeutic strategy for melanoma. AB - PURPOSE: Metastatic melanoma is considered one of the most aggressive malignant tumours, representing the deadliest form of skin cancer. Melanoma progression is associated with the abrogation of normal controls that limit cell proliferation, migration, and invasion, eventually leading to metastasis. Based on the variety of cellular mechanisms involved in metastatic progression, we aimed to evaluate the effect of inosine (50 MUM) and of the combination of Cl-IB-MECA (10 MUM) with paclitaxel (10 ng/mL) on several stages of melanoma progression. METHODS: Proliferation, migration, adhesion, invasion, and colony formation assays were performed on human C32 and A375 metastatic melanoma cells. Levels of ERK1/2 were also determined using an ELISA kit. Moreover, mouse aortic rings were treated with vascular endothelial growth factor in order to assess the microvessel sprouting (an indicator of angiogenesis) in the presence of the referred compounds. RESULTS: We demonstrate that inosine induced, through A3 adenosine receptor activation, proliferation, migration, adhesion, and invasion on C32 and A375 melanoma cells, although with dissimilar importance on the two melanoma cell lines. Inosine also increased colony formation on A375 cells. Levels of ERK1/2 were increased after inosine exposure and that increase was dependent on A3 adenosine receptor activation in both cell lines. Moreover, microvessel sprouting stimulated by inosine was decreased by the combination of Cl-IB-MECA with paclitaxel. CONCLUSIONS: Cl-IB-MECA combined with paclitaxel was able to impair almost all of the referred metastatic related mechanisms induced by inosine, making this approach a valuable tool for combinatory therapy against metastatic melanoma. PMID- 25119182 TI - Pharmacokinetics and pharmacogenomics of daunorubicin in children: a report from the Children's Oncology Group. AB - PURPOSE: We explored the impact of obesity, body composition, and genetic polymorphisms on the pharmacokinetics (PK) of daunorubicin in children with cancer. PATIENTS AND METHODS: Patients <=21 years receiving daunorubicin as an infusion of any duration <24 h for any type of cancer were eligible. Plasma drug concentrations were measured by high-performance liquid chromatography. Body composition was measured by dual-energy X-ray absorptiometry. Obesity was defined as a BMI >95% for age or as body fat >30%. NONMEM was used to perform PK model fitting. The Affymetrix DMET chip was used for genotyping. The impact of genetic polymorphisms was investigated using SNP/haplotype association analysis with estimated individual PK parameters. RESULTS: A total of 107 subjects were enrolled, 98 patients had PK sampling, and 50 patients underwent DNA analysis. Population estimates for daunorubicin clearance and volume of distribution were 116 L/m(2)/h +/- 14% and 68.1 L/m(2) +/- 24%, respectively. Apparent daunorubicinol clearance and volume of distribution were 26.8 L/m(2)/h +/- 5.6% and 232 L/m(2) +/- 10%, respectively. No effect of body composition or obesity was observed on PK. Forty-four genes with variant haplotypes were tested for association with PK. FMO3-H1/H3 genotype was associated with lower daunorubicin clearance than FMO3-H1/H1, p = 0.00829. GSTP1*B/*B genotype was also associated with lower daunorubicin clearance compared to GSTP1*A/*A, p = 0.0347. However, neither of these associations was significant after adjusting for multiple testing by either Bonferroni or false discovery rate correction. CONCLUSIONS: We did not detect an effect of body composition or obesity on daunorubicin PK. We found suggestive associations between FMO3 and GSTP1 haplotypes with daunorubicin PK that could potentially affect efficacy and toxicity. PMID- 25119184 TI - Population pharmacokinetic and covariate analysis of pertuzumab, a HER2-targeted monoclonal antibody, and evaluation of a fixed, non-weight-based dose in patients with a variety of solid tumors. AB - PURPOSE: To characterize the population pharmacokinetics (PK) of pertuzumab across clinical trials in a variety of solid tumors, evaluate the potential impact of patient characteristics on PK, and confirm the appropriateness of the fixed (non-weight-based) dose. METHODS: Pertuzumab concentration data collected following intravenous administration during eleven phase I/II studies and the pivotal phase III trial CLEOPATRA were analyzed using nonlinear mixed-effects modeling. The potential impact of patient and laboratory characteristics and HER2 target-related variables on pertuzumab PK were investigated in a covariate analysis. The final model was used to confirm selection of fixed, non-weight based dosing of pertuzumab, and to compare pertuzumab PK in CLEOPATRA with the other studies. RESULTS: The analysis included 4,525 serum concentration measurements from 481 patients with solid tumors. Pertuzumab PK in the 2-25 mg/kg dose range was described by a two-compartment linear model with first-order elimination. The elimination clearance and central compartment volume were 0.235 L/day, and 3.11 L, respectively, and the terminal elimination half-life was 18.0 days. Baseline serum albumin and lean body weight had statistically significant effects on pertuzumab clearance; however, simulations showed that the magnitude of their effects on pertuzumab exposure was minimal compared with overall variability and was not clinically relevant. Thus, variations in these factors do not require dose adjustments. CONCLUSIONS: The fixed, non-weight-based dosing of pertuzumab, 840 mg loading dose followed by a 420 mg maintenance dose every 3 weeks, in patients with the solid tumors in this analysis is well supported by the population pharmacokinetic modeling and simulation results. PMID- 25119186 TI - Evolution of treatment regimens in multiple myeloma: a social network analysis. AB - BACKGROUND: Randomized controlled trials (RCTs) are considered the gold standard for assessing the efficacy of new treatments compared to standard treatments. However, the reasoning behind treatment selection in RCTs is often unclear. Here, we focus on a cohort of RCTs in multiple myeloma (MM) to understand the patterns of competing treatment selections. METHODS: We used social network analysis (SNA) to study relationships between treatment regimens in MM RCTs and to examine the topology of RCT treatment networks. All trials considering induction or autologous stem cell transplant among patients with MM were eligible for our analysis. Medline and abstracts from the annual proceedings of the American Society of Hematology and American Society for Clinical Oncology, as well as all references from relevant publications were searched. We extracted data on treatment regimens, year of publication, funding type, and number of patients enrolled. The SNA metrics used are related to node and network level centrality and to node positioning characterization. RESULTS: 135 RCTs enrolling a total of 36,869 patients were included. The density of the RCT network was low indicating little cohesion among treatments. Network Betweenness was also low signifying that the network does not facilitate exchange of information. The maximum geodesic distance was equal to 4, indicating that all connected treatments could reach each other in four "steps" within the same pathway of development. The distance between many important treatment regimens was greater than 1, indicating that no RCTs have compared these regimens. CONCLUSION: Our findings show that research programs in myeloma, which is a relatively small field, are surprisingly decentralized with a lack of connectivity among various research pathways. As a result there is much crucial research left unexplored. Using SNA to visually and analytically examine treatment networks prior to designing a clinical trial can lead to better designed studies. PMID- 25119185 TI - Multiplexing spheroid volume, resazurin and acid phosphatase viability assays for high-throughput screening of tumour spheroids and stem cell neurospheres. AB - Three-dimensional cell culture has many advantages over monolayer cultures, and spheroids have been hailed as the best current representation of small avascular tumours in vitro. However their adoption in regular screening programs has been hindered by uneven culture growth, poor reproducibility and lack of high throughput analysis methods for 3D. The objective of this study was to develop a method for a quick and reliable anticancer drug screen in 3D for tumour and human foetal brain tissue in order to investigate drug effectiveness and selective cytotoxic effects. Commercially available ultra-low attachment 96-well round bottom plates were employed to culture spheroids in a rapid, reproducible manner amenable to automation. A set of three mechanistically different methods for spheroid health assessment (Spheroid volume, metabolic activity and acid phosphatase enzyme activity) were validated against cell numbers in healthy and drug-treated spheroids. An automated open-source ImageJ macro was developed to enable high-throughput volume measurements. Although spheroid volume determination was superior to the other assays, multiplexing it with resazurin reduction and phosphatase activity produced a richer picture of spheroid condition. The ability to distinguish between effects on malignant and the proliferating component of normal brain was tested using etoposide on UW228-3 medulloblastoma cell line and human neural stem cells. At levels below 10 uM etoposide exhibited higher toxicity towards proliferating stem cells, whereas at concentrations above 10 uM the tumour spheroids were affected to a greater extent. The high-throughput assay procedures use ready-made plates, open-source software and are compatible with standard plate readers, therefore offering high predictive power with substantial savings in time and money. PMID- 25119187 TI - Use of Kampo diagnosis in randomized controlled trials of Kampo products in Japan: a systematic review. AB - BACKGROUND: The Committee for Evidence-based Medicine (EBM) of the Japan Society for Oriental Medicine started compiling Evidence Reports of Kampo Treatment (EKAT) in 2007. EKAT is a compilation of structured abstracts of randomized controlled trials (RCTs), along with comments by a third party reviewer. As of 31 December, 2012, there were 378 RCTs of Kampo medicines in Japan. The primary research question of this study is "How frequently is Kampo diagnosis used in RCTs of Kampo medicines?" The secondary research question is "When is Kampo diagnosis used in RCTs?" MATERIALS AND METHODS: The structured abstract (SA) of each RCT article was reviewed to examine how Kampo diagnosis was used in RCTs, especially how Kampo diagnosis was used in the randomization process. RESULTS: Kampo diagnosis was used before randomization in 27 RCTs (7.1%), after randomization in 31 RCTs (8.2%), and not used in 320 RCTs (84.7%). Before randomization, Kampo diagnosis was used as a criterion for inclusion in 10 RCTs, criterion for exclusion in 9 RCTs, and criteria for both inclusion and exclusion in 2 RCTs. Kampo formulas were determined according to Kampo diagnosis in 7 RCTs. After randomization, subgroup analyses according to Kampo diagnosis were done in 27 RCTs, and grade of disease severity at Kampo diagnosis was used for analysis as an endpoint in 4 RCTs. CONCLUSIONS: Kampo diagnosis was used before randomization only in approximately 15% of RCTs, and the number of RCT articles using Kampo diagnosis after randomization was almost the same as that before randomization. Further studies to determine the good RCTs conforming to CONSORT requirements and good systematic reviews conforming to PRISMA requirements are needed to clarify the significance of Kampo diagnosis. PMID- 25119188 TI - Suberoylanilide hydroxamic acid induces ROS-mediated cleavage of HSP90 in leukemia cells. AB - Heat shock protein 90 (HSP90) is a molecular chaperone that supports stability of client proteins. We found that HSP90 was cleaved to 55 kDa protein after treatment with histone deacetylase (HDAC) inhibitors including suberoylanilide hydroxamic acid (SAHA) in several leukemia cell lines. We further analyzed molecular changes induced by SAHA in K562 cells. The SAHA-induced cleavage of HSP90 was blocked by a pan-caspase inhibitor, z-VAD-fmk, implying that the process is dependent on caspase activity. However, the experiments using antagonistic and agonistic Fas antibodies revealed that the cleavage of HSP90 was not dependent on Fas signaling. SAHA induced generation of reactive oxygen species (ROS), and the cleavage of HSP90 was blocked by a ROS scavenger N acetylcystein (NAC). We also confirmed that hydrogen peroxide (H2O2) induced cleavage of HSP90 in a similar manner. Caspase 2, 3, 4, 6, 8, and 10 were activated by treatment with SAHA, and the activities were reduced by the pretreatment of NAC. Treatment of the cells with caspase 10 inhihitor, but not other inhibitors of caspases activated by SAHA, prevented cleavage of HSP90 by SAHA. SAHA-induced ROS generation and HSP90 cleavage were dependent on newly synthesized unknown proteins. Taken together, our results suggest that the cleavage of HSP90 by SAHA is mediated by ROS generation and caspase 10 activation. HSP90 cleavage may provide an additional mechanism involved in anti cancer effects of HDAC inhibitors. PMID- 25119189 TI - Movement coordination during conversation. AB - Behavioral coordination and synchrony contribute to a common biological mechanism that maintains communication, cooperation and bonding within many social species, such as primates and birds. Similarly, human language and social systems may also be attuned to coordination to facilitate communication and the formation of relationships. Gross similarities in movement patterns and convergence in the acoustic properties of speech have already been demonstrated between interacting individuals. In the present studies, we investigated how coordinated movements contribute to observers' perception of affiliation (friends vs. strangers) between two conversing individuals. We used novel computational methods to quantify motor coordination and demonstrated that individuals familiar with each other coordinated their movements more frequently. Observers used coordination to judge affiliation between conversing pairs but only when the perceptual stimuli were restricted to head and face regions. These results suggest that observed movement coordination in humans might contribute to perceptual decisions based on availability of information to perceivers. PMID- 25119191 TI - Understanding reproducibility of human IVF traits to predict next IVF cycle outcome. AB - PURPOSE: Evaluating the failed IVF cycle often provides useful prognostic information. Before undergoing another attempt, patients experiencing an unsuccessful IVF cycle frequently request information about the probability of future success. Here, we introduced the concept of reproducibility and formulae to predict the next IVF cycle outcome. METHODS: The experimental design was based on the retrospective review of IVF cycle data from 2006 to 2013 in two different IVF centers and statistical analysis. The reproducibility coefficients (r) of IVF traits including number of oocytes retrieved, oocyte maturity, fertilization, embryo quality and pregnancy were estimated using the interclass correlation coefficient between the repeated IVF cycle measurements for the same patient by variance component analysis. The formulae were designed to predict next IVF cycle outcome. RESULTS: The number of oocytes retrieved from patients and their fertilization rate had the highest reproducibility coefficients (r = 0.81 ~ 0.84), which indicated a very close correlation between the first retrieval cycle and subsequent IVF cycles. Oocyte maturity and number of top quality embryos had middle level reproducibility (r = 0.38 ~ 0.76) and pregnancy rate had a relative lower reproducibility (r = 0.23 ~ 0.27). Based on these parameters, the next outcome for these IVF traits might be accurately predicted by the designed formulae. CONCLUSIONS: The introduction of the concept of reproducibility to our human IVF program allows us to predict future IVF cycle outcomes. The traits of oocyte numbers retrieved, oocyte maturity, fertilization, and top quality embryos had higher or middle reproducibility, which provides a basis for accurate prediction of future IVF outcomes. Based on this prediction, physicians may counsel their patients or change patient's stimulation plans, and laboratory embryologists may improve their IVF techniques accordingly. PMID- 25119190 TI - Resolving fluorophores by unmixing multispectral fluorescence tomography with independent component analysis. AB - It is a challenging problem to resolve and identify drug (or non-specific fluorophore) distribution throughout the whole body of small animals in vivo. In this article, an algorithm of unmixing multispectral fluorescence tomography (MFT) images based on independent component analysis (ICA) is proposed to solve this problem. ICA is used to unmix the data matrix assembled by the reconstruction results from MFT. Then the independent components (ICs) that represent spatial structures and the corresponding spectrum courses (SCs) which are associated with spectral variations can be obtained. By combining the ICs with SCs, the recovered MFT images can be generated and fluorophore concentration can be calculated. Simulation studies, phantom experiments and animal experiments with different concentration contrasts and spectrum combinations are performed to test the performance of the proposed algorithm. Results demonstrate that the proposed algorithm can not only provide the spatial information of fluorophores, but also recover the actual reconstruction of MFT images. PMID- 25119192 TI - Anti-mullerian hormone as a diagnostic and prognostic tool for PCOS patients. AB - PURPOSE: To determine whether the measurement of serum AMH can be used to diagnose PCOS and as a tool to predict the prognosis of PCOS. METHODS: This is a case-control study. Women of reproductive age (18-35 years) were recruited consecutively at a tertiary academic hospital during the period of March 2009 October 2011 and were divided into case (PCOS patients defined by the Rotterdam criteria) and control groups (non-PCOS patients). Menstrual history, clinical manifestations of hyperandrogenism, ovarian ultrasound assessments, and the levels of AMH, LH, FSH, and estradiol were collected. RESULTS: Seventy-one cases and 71 controls were recruited. AMH serum levels were significantly higher in PCOS patients than in controls. The Area Under the Curve (AUC) of the serum AMH assay in PCOS patients reached a value of 0.870. With a cut-off value of 4.45 ng/ml, the serum AMH level had a sensitivity of 76.1 % and a specificity of 74.6 %. The most common phenotypes of PCOS in this study were anovulation and polycystic ovary (63.4 %). However, the mean level of AMH was highest in the phenotypes of anovulation, polycystic ovaries and hyperandrogenism (11.1 ng/ml). CONCLUSIONS: In Indonesian women, AMH can be used as an alternative diagnostic criteria for PCOS patients with a cut-off value of 4.45 ng/ml. AMH value rise when hyperandrogenism is present therefore serum AMH levels also reflect the phenotype of PCOS. However, these findings must be confirmed with larger clinical studies. PMID- 25119193 TI - Response of red deer stags (Cervus elaphus) to playback of harsh versus common roars. AB - Red deer stags (Cervus elaphus) give two distinct types of roars during the breeding season, the "common roar" and the "harsh roar." Harsh roars are more frequent during contexts of intense competition, and characterized by a set of features that increase their perceptual salience, suggesting that they signal heightened arousal. While common roars have been shown to encode size information and mediate both male competition and female choice, to our knowledge, the specific function of harsh roars during male competition has not yet been studied. Here, we investigate the hypothesis that the specific structure of male harsh roars signals high arousal to competitors. We contrast the behavioral responses of free ranging, harem-holding stags to the playback of harsh roars from an unfamiliar competitor with their response to the playback of common roars from the same animal. We show that males react less strongly to sequences of harsh roars than to sequences of common roars, possibly because they are reluctant to escalate conflicts with highly motivated and threatening unfamiliar males in the absence of visual information. While future work should investigate the response of stags to harsh roars from familiar opponents, our observations remain consistent with the hypothesis that harsh roars may signal motivation during male competition, and illustrate how intrasexual selection can contribute to the diversification of male vocal signals. PMID- 25119194 TI - Optimal duration of anticoagulation. Provoked versus unprovoked VTE and role of adjunctive thrombophilia and imaging tests. AB - Once anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE) over years after a first episode is consistently around 30%. This risk is higher in patients with unprovoked than in those with (transient) provoked VTE, and among the latter in patients with medical than in those with surgical risk factors. Baseline parameters that have been found to be related to the risk of recurrent VTE are the proximal location of deep-vein thrombosis, obesity, old age, male sex and non-0 blood group, whereas the role of inherited thrombophilia is controversial. The persistence of residual vein thrombosis at ultrasound assessment has consistently been shown to increase the risk, as do persistently high values of D-dimer and the early development of the post-thrombotic syndrome. Although the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify subjects in whom anticoagulation can be safely discontinued. Moreover, new opportunities are offered by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving the same effectiveness; and by low-dose aspirin, which has the potential to prevent the occurrence of both venous and arterial thrombotic events. PMID- 25119203 TI - Save the children. PMID- 25119202 TI - Modeling the inflammatory response in the hypothalamus ensuing heat stroke: iterative cycle of model calibration, identifiability analysis, experimental design and data collection. AB - Heat Stroke (HS) is a life-threatening illness caused by prolonged exposure to heat that causes severe hyperthermia and nervous system abnormalities. The long term consequences of HS are poorly understood and deeper insight is required to find possible treatment strategies. Elevated pro- and anti-inflammatory cytokines during HS recovery suggest to play a major role in the immune response. In this study, we developed a mathematical model to understand the interactions and dynamics of cytokines in the hypothalamus, the main thermoregulatory center in the brain. Uncertainty and identifiability analysis of the calibrated model parameters revealed non-identifiable parameters due to the limited amount of data. To overcome the lack of identifiability of the parameters, an iterative cycle of optimal experimental design, data collection, re-calibration and model reduction was applied and further informative experiments were suggested. Additionally, a new method of approximating the prior distribution of the parameters for Bayesian optimal experimental design based on the profile likelihood is presented. PMID- 25119201 TI - Bone mineral density and vitamin D status in ambulatory and non-ambulatory children with cerebral palsy. AB - This study assessed distal femur and lumbar spine bone mineral density (BMD) Z scores in children with cerebral palsy. BMD z-score was lower in non-ambulatory than in ambulatory children. Somewhat surprisingly, among ambulatory children, those with better walking abilities had higher BMD z-score than those with more impaired walking ability. INTRODUCTION: Children with cerebral palsy (CP) have increased risk for low bone mineral density (BMD). The aim was to explore the difference in BMD at the distal femur and lumbar spine between ambulatory and non ambulatory children with CP and the relationship between vitamin D status and BMD. METHODS: Fifty-one children (age range 8-18 years; 20 girls) with CP participated. Their BMD Z-scores were measured in the lumbar spine and the distal femur using dual X-ray absorptiometry, and 25-hydroxy-vitamin D (25-OHD) concentrations were measured in serum. Children with GMFCS level I-III were defined as 'walkers' while children with level IV-V were defined as 'non-walkers. RESULTS: Non-walkers had lower mean BMD Z-scores (range -1.7 to -5.4) than walkers at all sites (range -0.8 to -1.5). Among walkers, BMD Z-scores at the distal femur were lower in those with GMFCS level II than with level I (p values < 0.004). A similar difference was found between the affected and unaffected limb in children with hemiplegia. Mean 25-OHD concentration was 45 nmol/L (SD = 18); lower in walkers (mean = 41 nmol/L; SD = 18) than in non-walkers (mean = 53 nmol/L; SD = 19; p = 0.041). There were no correlations between 25-OHD and BMD z scores. CONCLUSIONS: The main predictor of low BMD Z-scores in the distal femur was the inability to walk, but the results suggest that the degree of the neuromotor impairment may also be a significant predictor. Vitamin D status did not correlate with BMD z-scores. PMID- 25119204 TI - Future computing. PMID- 25119217 TI - Native ecosystems blitzed by drought. PMID- 25119205 TI - China should aim for a total cap on emissions. PMID- 25119218 TI - Health check for deep-sea mining. PMID- 25119219 TI - Teen drug use gets supersize study. PMID- 25119220 TI - US assesses virus of the Caribbean. PMID- 25119221 TI - Online collaboration: Scientists and the social network. PMID- 25119222 TI - Society: Don't blame the mothers. PMID- 25119225 TI - Conservation: White possums must stay cool to survive. PMID- 25119226 TI - Centenary: Russian stamp to honour physicist. PMID- 25119227 TI - Transgenic crops: Mexican GM maize rift is not so simple. PMID- 25119228 TI - Sexual harassment: Create ethics codes to curb sex abuse. PMID- 25119229 TI - Neuroscience: What females really want. PMID- 25119230 TI - Solar system: Sandcastles in space. PMID- 25119231 TI - Condensed-matter physics: Glasses made from pure metals. PMID- 25119232 TI - Astronomical instrumentation: Atmospheric blurring has a new enemy. PMID- 25119233 TI - Limits on fundamental limits to computation. AB - An indispensable part of our personal and working lives, computing has also become essential to industries and governments. Steady improvements in computer hardware have been supported by periodic doubling of transistor densities in integrated circuits over the past fifty years. Such Moore scaling now requires ever-increasing efforts, stimulating research in alternative hardware and stirring controversy. To help evaluate emerging technologies and increase our understanding of integrated-circuit scaling, here I review fundamental limits to computation in the areas of manufacturing, energy, physical space, design and verification effort, and algorithms. To outline what is achievable in principle and in practice, I recapitulate how some limits were circumvented, and compare loose and tight limits. Engineering difficulties encountered by emerging technologies may indicate yet unknown limits. PMID- 25119234 TI - Cohesive forces prevent the rotational breakup of rubble-pile asteroid (29075) 1950 DA. AB - Space missions and ground-based observations have shown that some asteroids are loose collections of rubble rather than solid bodies. The physical behaviour of such 'rubble-pile' asteroids has been traditionally described using only gravitational and frictional forces within a granular material. Cohesive forces in the form of small van der Waals forces between constituent grains have recently been predicted to be important for small rubble piles (ten kilometres across or less), and could potentially explain fast rotation rates in the small asteroid population. The strongest evidence so far has come from an analysis of the rotational breakup of the main-belt comet P/2013 R3 (ref. 7), although that was indirect and poorly constrained by observations. Here we report that the kilometre-sized asteroid (29075) 1950 DA (ref. 8) is a rubble pile that is rotating faster than is allowed by gravity and friction. We find that cohesive forces are required to prevent surface mass shedding and structural failure, and that the strengths of the forces are comparable to, though somewhat less than, the forces found between the grains of lunar regolith. PMID- 25119235 TI - Formation of monatomic metallic glasses through ultrafast liquid quenching. AB - It has long been conjectured that any metallic liquid can be vitrified into a glassy state provided that the cooling rate is sufficiently high. Experimentally, however, vitrification of single-element metallic liquids is notoriously difficult. True laboratory demonstration of the formation of monatomic metallic glass has been lacking. Here we report an experimental approach to the vitrification of monatomic metallic liquids by achieving an unprecedentedly high liquid-quenching rate of 10(14) K s(-1). Under such a high cooling rate, melts of pure refractory body-centred cubic (bcc) metals, such as liquid tantalum and vanadium, are successfully vitrified to form metallic glasses suitable for property interrogations. Combining in situ transmission electron microscopy observation and atoms-to-continuum modelling, we investigated the formation condition and thermal stability of the monatomic metallic glasses as obtained. The availability of monatomic metallic glasses, being the simplest glass formers, offers unique possibilities for studying the structure and property relationships of glasses. Our technique also shows great control over the reversible vitrification-crystallization processes, suggesting its potential in micro electromechanical applications. The ultrahigh cooling rate, approaching the highest liquid-quenching rate attainable in the experiment, makes it possible to explore the fast kinetics and structural behaviour of supercooled metallic liquids within the nanosecond to picosecond regimes. PMID- 25119238 TI - Developing a genetic fuzzy system for risk assessment of mortality after cardiac surgery. AB - Cardiac events could be taken into account as the leading causes of death throughout the globe. Such events also trigger an undesirable increase in what treatment procedures cost. Despite the giant leaps in technological development in heart surgery, coronary surgery still carries the high risk of the mortality. Besides, there is still a long way ahead to accurately predict and assess the mortality risk. This study is an attempt to develop an expert system for the risk assessment of mortality following the cardiac surgery. The developed system involves three main steps. In the first step, a filtering feature selection method is applied to select the best features. In the second step, an ad hoc data driven method is utilized to generate the preliminary fuzzy inference system. Finally, a hybrid optimization method is presented to select the optimum subset of the rules. The study relies on 1,811 samples to evaluate the diagnosis performance of the proposed system. The obtained classification accuracy is very promising with regard to other benchmark classification methods including binary logistic regression (LR) and multilayer perceptron neural network (MLP) with the same attributes. The developed system leads to 100% sensitivity and 84.7% specificity, while LR and MLP methods statistically come up with lower figures (65, 78.6 and 65%, 75.8%), respectively. Now, a fuzzy supportive tool can be potentially taken as an alternative for the current mortality risk assessment system that are applied in coronary surgeries, and are chiefly based on crisp database. PMID- 25119237 TI - Transport networks and inequities in vaccination: remoteness shapes measles vaccine coverage and prospects for elimination across Africa. AB - Measles vaccination is estimated to have averted 13.8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (?50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered. PMID- 25119239 TI - Construction the model on the breast cancer survival analysis use support vector machine, logistic regression and decision tree. AB - The aim of the paper is to use data mining technology to establish a classification of breast cancer survival patterns, and offers a treatment decision-making reference for the survival ability of women diagnosed with breast cancer in Taiwan. We studied patients with breast cancer in a specific hospital in Central Taiwan to obtain 1,340 data sets. We employed a support vector machine, logistic regression, and a C5.0 decision tree to construct a classification model of breast cancer patients' survival rates, and used a 10 fold cross-validation approach to identify the model. The results show that the establishment of classification tools for the classification of the models yielded an average accuracy rate of more than 90% for both; the SVM provided the best method for constructing the three categories of the classification system for the survival mode. The results of the experiment show that the three methods used to create the classification system, established a high accuracy rate, predicted a more accurate survival ability of women diagnosed with breast cancer, and could be used as a reference when creating a medical decision-making frame. PMID- 25119240 TI - Analysis of laryngeal fractures in decomposed bodies using microfocus computed tomography (mfCT). AB - Postmortem computed tomography (CT) is now routinely performed in forensic autopsies. Microfocus computed tomography (mfCT) has attracted recent attention because it can provide more detailed information than routine postmortem CT can. This feasibility study evaluated the usefulness of mfCT for examination of the hyoid bone and thyroid cartilage in cases of suspected strangulation, where advanced decomposition precludes detection of petechial hemorrhages and hemorrhages adjacent to fractures. The results show that mfCT was useful for identification of thin fracture lines in the fragile laryngeal structures. We suggest that mfCT should be considered for forensic autopsies in cases of suspected strangulation with advanced decomposition. PMID- 25119241 TI - High variation in hypoxanthine determination after analytical treatment of vitreous humor samples. AB - In the field of legal medicine the correct determination of the time of death is of great importance because an error in calculating the post-mortem interval (PMI) could be crucial in a criminal investigation. The quantification of hypoxanthine (Hx) concentration in the vitreous humor (VH) as a means to estimate PMI is useful when dealing with a recent time interval of death and has several advantages over other biological matrices. However, due to its viscous nature, VH has to be liquefied prior to its analysis, and the different procedures to liquefy it may cause alterations in Hx concentration, and hence in estimation of PMI. The aim of this study was to determine differences in Hx concentration after applying several pre-analytical treatments to different aliquots of the same VH sample. Enzymatic digestion, sonication, centrifugation and heat were the liquefying methods applied to reduce the viscosity of 105 VH samples. Analysis was performed using solid phase extraction and liquid chromatography in tandem with mass spectrometry. Statistically significant differences in the measured Hx concentrations were found between enzymatic digestion and the other three methods analyzed (sonication, centrifugation, and heat). Additionally, high data dispersion was found under heat treatment but was not observed for centrifugation or sonication, where similar and more moderate results were found. We conclude that high variations in Hx determination are observed when enzymatic digestion or heat treatment is used and we therefore recommend sonication or centrifugation to quantify Hx concentration in the VH. PMID- 25119242 TI - Is cerebral swelling following cranio-cerebral trauma instantaneous? An insight into the Byard and Vink proposition. PMID- 25119244 TI - Forensic text books: how to publish and perish, all at the same time. PMID- 25119243 TI - Is the phenomenon of "crow's feet" in cases of high-voltage accidents a vital reaction? PMID- 25119245 TI - Improvement of Aspergillus oryzae NRRL 3484 by mutagenesis and optimization of culture conditions in solid-state fermentation for the hyper-production of extracellular cellulase. AB - Spore suspensions of Aspergillus oryzae NRRL 3484 were subjected to mutagenesis using ultraviolet-irradiation followed by chemical treatments to improve the biosynthesis of cellulase. Ten mutant strains namely UEAC7, UEAR5, UNAC4, UNAC16, UNAR19, UNBC7, UNBR3, UNBR10, UNBR23 and UNBR25 were selected and their extracellular cellulase activities were assayed. Mutant UNAC4 gave the highest cellulase production [2,455 +/- 28 U/g-dry substrate (ds) for filter paper-ase (FP-ase)] in a yield 4-fold exceeding that of the wild type strain (578 +/- 5.0 U/g-ds for FP-ase). Rice straw (RS) was used as a sole carbon source for the enzyme production at a concentration of 10 % (w/v). Maximum cellulase production was achieved at initial medium pH 5.5, initial moisture content 77 % and an incubation temperature 28 degrees C on the fifth day of growth. NH4Cl proved to be the suitable added nitrogen source for maximum enzyme production followed by peptone. These results clearly indicate the cost-effectiveness of solid state fermentation technology in the economic production of extracellular cellulase. The hyper-production of cellulase by mutant strain UNAC4 has potential for industrial processes that convert lignocellulosic material (e.g. RS) into products of commercial value such as glucose and biofuels. PMID- 25119246 TI - Soil bacterial diversity in degraded and restored lands of Northeast Brazil. AB - Land degradation deteriorates biological productivity and affects environmental, social, and economic sustainability, particularly so in the semi-arid region of Northeast Brazil. Although some studies exist reporting gross measures of soil microbial parameters and processes, limited information is available on how land degradation and restoration strategies influence the diversity and composition of soil microbial communities. In this study we compare the structure and diversity of bacterial communities in degraded and restored lands in Northeast Brazil and determine the soil biological and chemical properties influencing bacterial communities. We found that land degradation decreased the diversity of soil bacteria as indicated by both reduced operational taxonomic unit (OTU) richness and Shannon index. Soils under native vegetation and restoration had significantly higher bacterial richness and diversity than degraded soils. Redundancy analysis revealed that low soil bacterial diversity correlated with a high respiratory quotient, indicating stressed microbial communities. By contrast, soil bacterial communities in restored land positively correlated with high soil P levels. Importantly, however, we found significant differences in the soil bacterial community composition under native vegetation and in restored land, which may indicate differences in their functioning despite equal levels of bacterial diversity. PMID- 25119247 TI - Low expression of microRNA-30c promotes invasion by inducing epithelial mesenchymal transition in non-small cell lung cancer. AB - MicroRNA (miR)-30c has been identified as a tumor suppressor gene in numerous diseases. Aberrant miR-30c expression has been associated with the invasion of different types of cancer. However, the potential mechanisms underlying the association between miR-30c and invasion has been poorly elucidated in non-small cell lung cancer (NSCLC). In the present study, quantitative polymerase chain reaction demonstrated that the expression of miR-30c was reduced in lung cancer specimens (n=85). Suppressing the expression of miR-30c promoted the invasion of A549 cells, while overexpressed miR-30c inhibited the invasion of A549 cells. Furthermore, aberrant miR-30c expression was able to control the expression levels of markers (E-cadherin, snail and vimentin) of epithelial mesenchymal transition (EMT). In conclusion, miR-30c regulated the invasion of NSCLC cells and low miR-30 levels induced EMT. PMID- 25119248 TI - [Regulating the internet: a comparative analysis of Brazil, Chile, Spain, the US, and France]. AB - Global governance is of key concern in the current debate over the workings of the world's computer network, and Brazil has played a notable role in this process, especially after approval of the Marco Civil da Internet (law 12.965, april 23, 2014), which defines Brazil's regulatory framework for the internet. Dubbed the internet bill of rights, this law sets out the principles, guarantees, rights, and duties of internet users and providers in Brazil. Based on the fundamental categories of net neutrality, internet users' right to privacy, and copyright discussions from the perspective of intellectual property, the article offers a comparative analysis of regulations in five countries: Brazil, Chile, Spain, the US, and France. PMID- 25119249 TI - [Obsessions before Freud: history and clinical practice]. AB - The article analyses the significance of the concept of "obsession" in nineteenth century alienism. From a clinical point of view, Esquirol's description was completed by other authors (Jules Falret, Legrand du Saulle). In the area of psychopathological studies, French alienism, with Morel's emotional delirium or Janet's psychasthenia, defended the emotional theory, as opposed to the intellectual disorder proposed by German doctors. Lastly, the importance of the cultural framework is stressed in the appearance of obsessive symptoms and their interpretation. Along these lines, the article discusses the relationship of religious scruples to melancholy or the appearance of diagnostic categories subject to fin de siecle codes and mentalities. PMID- 25119252 TI - Statistics commentary series: commentary #4--relative risk and the number needed to treat. PMID- 25119251 TI - Rifampicin improves neuronal apoptosis in LPS-stimulated co-cultured BV2 cells through inhibition of the TLR-4 pathway. AB - Agents inhibiting microglial activation are attracting attention as candidate drugs for neuroprotection in neurodegenerative diseases. Recently, researchers have focused on the immunosuppression induced by rifampicin. Our previous study showed that rifampicin inhibits the production of lipopolysaccharide (LPS) induced pro-inflammatory mediators and improves neuron survival in inflammation; however, the mechanism through which rifampicin inhibits microglial inflammation and its neuroprotective effects are not completely understood. In this study, we examined the effects of rifampicin on morphological changes induced by LPS in murine microglial BV2 cells. Then we investigated, in BV2 microglia, the effects of rifampicin on two signaling pathway componentss stimulated by LPS, the Toll like receptor-4 (TLR-4) and the nuclear factor-kappaB (NF-kappaB). In addition, we co-cultured BV2 microglia and neurons to observe the indirect neuroprotective effects of rifampicin. Rifampicin inhibited LPS-stimulated expression of the TLR 4 gene. When neurons were co-cultured with LPS-stimulated BV2 microglia, pre treatment with rifampicin increased neuronal viability and reduced the number of apoptotic cells. Taken together, these findings suggest that rifampicin, with its anti-inflammatory properties, may be a promising agent for the treatment of neurodegenerative diseases. PMID- 25119250 TI - The toxicology investigators consortium case registry-the 2013 experience. AB - The Toxicology Investigators Consortium (ToxIC) Case Registry was established in 2010 by the American College of Medical Toxicology. The Registry includes all medical toxicology consultations performed at participating sites. This report summarizes the Registry data for 2013. A query of the ToxIC Registry was carried out for the dates of January 1 through December 31, 2013. Specific data reviewed for analysis included demographics (age, gender), source of consultation, reasons for consultation, agents involved in toxicological exposures, signs, symptoms and clinical findings, and treatment. A total of 8,598 cases were entered into the Registry in 2013. Females accounted for 49.2 % of cases, males for 47.7 %, and gender was not reported in 3.1 %. The majority of patients (63.4 %) were adults between the ages of 19 and 65 years. There were 93 fatalities (1.1 %). Most referrals for medical toxicology consultation originated from the emergency department (59.7 %) or inpatient services (16.7 %). Exposures to pharmaceutical products (intentional and unintentional) made up 50.0 % of cases. Illicit drug abuse (8.0 %) and adverse drug reactions (ADRs) (4.8 %) were the next most frequent reasons for consultation. Similar to past years, nonopioid analgesics, sedative-hypnotics, and opioids were the most commonly encountered agents. Symptoms or clinical findings were documented in 71.1 % of patients. Of all cases, 54.6 % required some form of medical treatment (antidotes, antivenom, chelation, specific types of supportive care). This report serves as a comprehensive survey of medical toxicology practice within participating institutions. Prior trends continued to apply this year and indicate analgesic (opioid and nonopioid), sedative-hypnotic/muscle relaxant agents, illicit drug use, and ADRs continue to be major toxicological problems. Cases requiring medical toxicology consultation in 2013 predominantly involved pharmaceuticals and illicit drugs. Reasons for these drug exposures were diverse and included intentional overdose, unintentional exposure, withdrawal syndromes, and ADRs. Nonopioid analgesics, sedative-hypnotic agents, and opioids remained the most frequently encountered agent classes. While over half of cases required some form of medical treatment, fatalities were uncommon. PMID- 25119254 TI - The three-dimensional shape analysis of the M1 segment of the middle cerebral artery using MRA at 3T. AB - INTRODUCTION: The M1 segment of the middle cerebral artery (MCA) is of great importance to neurosurgery and interventional radiology. The purpose of this study was to describe the M1 segment in three dimensions based on shape projection using magnetic resonance angiography (MRA). METHODS: A three-view method was established and used in the retrospective analysis of 717 M1 segments derived from 3D-TOF MRA images. In this method, the M1 segment was first projected on three orthogonal planes (axial, coronary, and sagittal plane); the courses of the projected vessels were classified as line-shape, C-shape, or S shape on each orthogonal plane; and then the actual parameters, including internal diameter and so on, were measured on the projected images. The shape classifications and the measured parameters were efficient methods of describing the M1 segment. Twelve geometric models of the vessels were reconstructed and were compared with those from an actual validation method. RESULTS: The 3D shape of the M1 segment in the 3D orthogonal views was not uniform. Only 17.3 % M1 segments were straight, 43.5 % followed plane curves, and nearly 40 % were tortuous in 3D space. The probability distributions of shape classifications changed with age. The proportion of the tortuous vessels increased with age. We also showed that the three-view method is effective with a volume relative error of less than 13 %. CONCLUSION: The three-view method is convenient for describing the 3D morphology, including the shape information, of the M1 segment. It is a potential method for planning and predicting risk in neurosurgery/neurointervention. PMID- 25119253 TI - The effects of hemorrhagic parenchymal infarction on the establishment of sensori motor structural and functional connectivity in early infancy. AB - INTRODUCTION: The objective of the study was to characterize alterations of structural and functional connectivity within the developing sensori-motor system in infants with focal perinatal brain injury and at high risk of cerebral palsy. METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were used to study the developing functional and structural connectivity framework in six infants born prematurely at term equivalent age. This was first characterised in three infants without focal pathology, which was then compared to that derived from three infants with unilateral haemorrhagic parenchymal infarction and a subsequent focal periventricular white matter lesion who developed later haemiparesis. RESULTS: Functional responses to passive hand movement were in the contralateral perirolandic cortex, regardless of focal pathology. In infants with unilateral periventricular injury, afferent thalamo cortical tracts appeared to have developed compensatory trajectories which circumvented areas of damage. In contrast, efferent corticospinal tracts showed marked asymmetry at term equivalent age following focal brain injury. Sensori motor network analysis suggested that inter-hemispheric functional connectivity is largely preserved despite pathology and that impairment may be associated with adverse neurodevelopmental outcome. CONCLUSION: Following focal perinatal brain injury, altered structural and functional connectivity is already present and can be characterized with MRI at term equivalent age. The results of this small case series suggest that these techniques may provide valuable new information about prognosis and the pathophysiology underlying cerebral palsy. PMID- 25119255 TI - Mechanical thrombectomy in patients with acute vertebrobasilar occlusion using the Trevo device: a single-centre experience. AB - INTRODUCTION: The purpose of this study is to investigate the efficacy and safety of mechanical thrombectomy in patients with acute vertebrobasilar artery occlusion (VBAO) using the Trevo StentrieverTM device. METHODS: Twenty patients diagnosed with VBAO underwent digital subtraction angiography (DSA) with the intention to perform mechanical thrombectomy with stent-retrievers between August 2011 and October 2013. Two patients were excluded because another device was primarily used; in two other patients, thrombectomy was not possible. RESULTS: Thrombectomy with the Trevo device was performed in 16 patients. The StentrieverTM was used either as the sole device (56.3 %) or in conjunction with up to four additional devices or techniques. Thirty-three clot retrieval manoeuvres were performed (mean 2.1 +/- 1.3, range 1-5); the device could be deployed and retrieved in all manoeuvres (100 %). No device-related complications occurred. Mean duration of the endovascular intervention was 71.8 min (+/-39.9; range 22-144). Complete or near complete recanalization (thrombolysis in cerebral infarction (TICI) >=2b) was achieved in 13 patients (81.3 %). Eleven patients (68.8 %) survived and seven patients (43.8 %) showed a good clinical outcome at discharge, defined as modified Rankin Scale (mRS) 0-2 or National Institute of Health Stroke Scale (NIHSS) improvement >=10 points. Including the two patients in whom thrombectomy was not possible, successful recanalization, good clinical outcome and survival were achieved in 72.2, 38.9 and 61.1 %, respectively. CONCLUSIONS: Thrombectomy in patients with acute VBAO using the Trevo StentrieverTM-either as the sole device or in conjunction with other devices-is feasible and seems to be similarly effective and safe as in the anterior circulation compared to reported data in the literature. PMID- 25119257 TI - Transverse myelitis extended to disseminated encephalitis in systemic lupus erythematosus: Histological evidence for vasculitis. AB - A 42-year-old woman was admitted due to systemic lupus erythematosus complicated with glomerulonephritis and pulmonary hypertension. During the treatment for these complications, she presented motor paresis and sensory loss caused by transverse myelitis. In spite of methyl prednisolone pulse therapy, she further developed acute confusional state due to disseminated encephalitis and fell into respiratory arrest. On laboratory examination, elevation of anti-NR2 antibodies in serum as well as in cerebrospinal fluid was noted. Although she recovered from the disseminated encephalitis after extensive treatment with high doses of corticosteroid and intravenous cyclophosphamide, she suddenly died of pulmonary hypertension. Autopsy findings confirmed the presence of liquefaction necrosis in the entire circumference of the whole spinal cord along with intimal hyperplasia and obliteration of the small arteries, accompanied by mononuclear cell infiltration and disruption of internal elastic lamina. It is therefore most likely that our patient developed longitudinal transverse myelitis through spinal cord vasculitis, which extended to brainstem and brain parenchyma, leading to the development of disseminated encephalitis. PMID- 25119256 TI - Injury of the lower ascending reticular activating system in patients with hypoxic-ischemic brain injury: diffusion tensor imaging study. AB - INTRODUCTION: Many studies have reported on vulnerable areas and neural tracts of the brain after hypoxic-ischemic brain injury (HI-BI). However, little is known about injury of the ascending reticular activating system (ARAS). We attempted to investigate on injury of the lower portion of the ARAS in patients with HI-BI using diffusion tensor tractography (DTT). METHODS: Fourteen consecutive patients with HI-BI and 10 control subjects were recruited for this study. We classified the patients into two subgroups according to the preservation of arousal: subgroup A (eight patients)-intact arousal and subgroup B (six patients)-impaired arousal. The lower portion of the ARAS between the pontine reticular formation and the thalamus was reconstructed using the probabilistic tractography method. Fractional anisotropy (FA), mean diffusivity (MD), and tract volume (TV) were measured. RESULTS: The FA value and TV were decreased in subgroup B compared with those of the control group, although no difference was observed in the MD value (p < 0.05). However, for all DTT parameters, no difference was observed between subgroup A and the control group and between subgroup A and subgroup B (p > 0.05). CONCLUSION: Injury of the lower portion of the ARAS was found between the pontine reticular formation and the thalamus in patients with impaired arousal after HI-BI. We believe that analysis using DTT could be helpful in the evaluation of patients with impaired arousal after HI-BI. PMID- 25119258 TI - Are Sjogren's syndrome and IgG4-related disease able to coexist? PMID- 25119259 TI - Ultrasonography and magnetic resonance imaging findings of rheumatoid arthritis like arthritis in a patient with adult T-cell leukemia. AB - A 43-year-old Japanese woman with adult T-cell leukemia (ATL) developed rheumatoid arthritis-like polyarthritis with dermatitis and skin erosion. Her rheumatoid factor and C-reactive protein results were positive. Musculoskeletal ultrasonography showed intra-articular and peritendinous power Doppler signal positive synovitis. Plain magnetic resonance imaging showed synovitis of the above lesion and remarkable bone marrow edema/osteitis. She was diagnosed as having ATL-associated arthritis based on the invasion of ATL cells by skin biopsy at the arthritis lesion. PMID- 25119260 TI - The roles of myeloid-derived suppressor cells in transplantation. AB - CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs) are an important regulatory innate cell population and have significant inhibitory effect on T cell-mediated responses. In addition to their negative role in cancer development, MDSCs also exert strong regulatory effects on transplantation and autoimmunity. In many transplantation models, such as bone marrow transplant, renal transplant, heart transplant and skin transplant settings, MDSCs accumulate and have inhibitory effect on graft rejection. However, the inducing factors, detailed phenotype and functional molecular mediators of MDSCs are significantly different in various transplant models. With their strong suppressive activity, MDSCs could become a potential clinical therapy during transplantation tolerance induction and the combination of the MDSCs with other immunoregulatory cells or immunosuppressive drugs is an intriguing protocol in the future. In this review, we will summarize MDSC expansion, activation and induction in different transplantation models and discuss the effects of immunoregulatory cells and immunosuppressive drugs on MDSCs in transplant settings. PMID- 25119261 TI - Facile and rapid synthesis of Pd nanodendrites for electrocatalysis and surface enhanced Raman scattering applications. AB - Numerous properties from metal nanostructures can be tuned by controlling both their size and shape. In particular, the latter is extremely important because the type of crystalline surface affects the surface electronic density. This paper describes a simple approach to the synthesis of highly-structured, anisotropic palladium nanostructured dendrites. They were obtained using an eco friendly biomolecule 5-hydroxytryptophan, which acts as both a reducing and stabilizing agent. The growth mechanism is proposed for the evolution of dendrites morphology. It was found that the concentration of 5-hydroxytryptophan played a vital role on the morphology of the nanostructured Pd dendrites. This nanomaterial shows enhanced electrocatalytic performance towards the oxidation of formic acid, and it exhibits surface-enhanced Raman scattering properties towards the prostate specific antigen. These properties may be explored in fuel cells and biosensors, respectively. PMID- 25119262 TI - Spray pyrolysis of CZTS nanoplatelets. AB - We demonstrate that copper-zinc-tin-sulphide nanoplatelets can be directly grown onto a molybdenum-coated substrate using spray pyrolysis starting from a mixture of metal thiocarbamates precursors. The structure and phase purity of the nanoplatelets is discussed in detail. PMID- 25119264 TI - Unusual assembly of lacunary heteropolymolybdates with cyanometalate fragment. AB - Two new cyanide-bridged heteropolymolybdate complexes have been synthesized by a facile self-assembly process in aqueous solution, which demonstrates a successful tactic to incorporate the cyanometalate fragment into lacunary heteropolymolybdate. Magnetic investigation showed that complex 2 exhibits slow magnetic relaxation behavior. PMID- 25119263 TI - Sex chromosomes and karyotype of the (nearly) mythical creature, the Gila monster, Heloderma suspectum (Squamata: Helodermatidae). AB - A wide variety of sex determination systems exist among squamate reptiles. They can therefore serve as an important model for studies of evolutionary transitions among particular sex determination systems. However, we still have only a limited knowledge of sex determination in certain important lineages of squamates. In this respect, one of the most understudied groups is the family Helodermatidae (Anguimorpha) encompassing the only two venomous species of lizards which are potentially lethal to human beings. We uncovered homomorphic ZZ/ZW sex chromosomes in the Gila monster (Heloderma suspectum) with a highly heterochromatic W chromosome. The sex chromosomes are morphologically similar to the ZZ/ZW sex chromosomes of monitor lizards (Varanidae). If the sex chromosomes of helodermatids and varanids are homologous, female heterogamety may be ancestral for the whole Anguimorpha group. Moreover, we found that the karyotype of the Gila monster consists of 2n = 36 chromosomes (14 larger metacentric chromosomes and 22 acrocentric microchromosomes). 2n = 36 is the widely distributed chromosomal number among squamates. In his pioneering works representing the only previous cytogenetic examination of the family Helodermatidae, Matthey reported the karyotype as 2n = 38 and suggested a different chromosomal morphology for this species. We believe that this was probably erroneously. We also discovered a strong accumulation of telomeric sequences on several pairs of microchromosomes in the Gila monster, which is a trait documented relatively rarely in vertebrates. These new data fill an important gap in our understanding of the sex determination and karyotype evolution of squamates. PMID- 25119266 TI - Perspectives in pediatric pathology, chapter 1. Normal development of testicular structures: from the bipotential gonad to the fetal testis. PMID- 25119265 TI - Elucidating the role of DEPTOR in Alzheimer's disease. AB - The mammalian or mechanistic target of rapamycin (mTOR) is a Ser/Thr protein kinase that, in response to nutrient stimulation, regulates cellular growth, proliferation, survival, protein synthesis and gene transcription. It has also been implicated in Alzheimer's disease (AD) with neuronal cells and hippocampal slices of AD transgenic mice experiencing dysregulated mTOR and synaptic plasticity in response to treatment with the toxic amyloid beta (Abeta(1-42)) peptide, which has been implicated in AD. DEP domain-containing mTOR-interacting protein (DEPTOR) is a protein which can bind to mTOR and cause its inhibition, and functions as a regulatory protein of mTOR to control its activity. The inhibition of mTOR has been shown to have a neuroprotective effect; in an animal model, it was shown to protect against Abeta-induced neurotoxicity. In the present study, to investigate to role of DEPTOR in a model of AD, we neuronally differentiated the SH-SY5Y cell line and examined the effects of treatment with an Abeta(42) peptide, thus mimicking plaque formation. This resulted in a significant increase in mTOR and a significant decrease in DEPTOR expression compared to the unstimulated controls. Moreover, to the best of our knowledge, we demonstrate for the first time a reduction in the protein level of DEPTOR in the precentral gyrus, postcentral gyrus and occipital lobe of a brain with AD compared to a normal control, as well as a significant reduction in DEPTOR expression in samples from late-onset AD (LOAD) compared to early-onset familial AD (EOFAD). The reduction in DEPTOR expression in cases of AD compared to healthy controls can lead to an augmentation of mTOR signalling, leading to Abeta accumulation, which in turn leads to a further reduction in DEPTOR expression. This results in the accumulation of amyloid plaque, shifting the balance from neuroprotection to neurodegeneration. PMID- 25119267 TI - Familiarity with interest breeds gossip: contributions of emotion, expectation, and reputation. AB - Although gossip serves several important social functions, it has relatively infrequently been the topic of systematic investigation. In two experiments, we advance a cognitive-informational approach to gossip. Specifically, we sought to determine which informational components engender gossip. In Experiment 1, participants read brief passages about other people and indicated their likelihood to share this information. We manipulated target familiarity (celebrity, non-celebrity) and story interest (interesting, boring). While participants were more likely to gossip about celebrity than non-celebrity targets and interesting than boring stories, they were even more likely to gossip about celebrity targets embedded within interesting stories. In Experiment 2, we additionally probed participants' reactions to the stories concerning emotion, expectation, and reputation information conveyed. Analyses showed that while such information partially mediated target familiarity and story interest effects, only expectation and reputation accounted for the interactive pattern of gossip behavior. Our findings provide novel insights into the essential components and processing mechanisms of gossip. PMID- 25119268 TI - Slow magnetic relaxation in a mononuclear eight-coordinate cobalt(II) complex. AB - The quest for the single-molecular magnets (SMMs) based on mononuclear transition metal complexes is focused on the low-coordinate species. No transition-metal complex with a coordination number of eight has been shown to exhibit SMM properties. Here the magnetic studies have been carried out for a mononuclear, eight-coordinate cobalt(II)-12-crown-4 (12C4) complex [Co(II)(12C4)2](I3)2(12C4) (1) with a large axial zero-field splitting. Magnetic measurements show field induced, slow magnetic relaxation under an applied field of 500 Oe at low temperature. The magnetic relaxation time tau was fitted by the Arrhenius model to afford an energy barrier of Ueff = 17.0 cm(-1) and a preexponential factor of tau0 = 1.5 * 10(-6) s. The work here presents the first example of the eight coordinate, mononuclear, 3d metal complex exhibiting the slow magnetic relaxation. PMID- 25119272 TI - Vertebral artery dissection as cause of sulcal artery syndrome. PMID- 25119269 TI - Development of a multi-species biotic ligand model predicting the toxicity of trivalent chromium to barley root elongation in solution culture. AB - Little knowledge is available about the influence of cation competition and metal speciation on trivalent chromium (Cr(III)) toxicity. In the present study, the effects of pH and selected cations on the toxicity of trivalent chromium (Cr(III)) to barley (Hordeum vulgare) root elongation were investigated to develop an appropriate biotic ligand model (BLM). Results showed that the toxicity of Cr(III) decreased with increasing activity of Ca(2+) and Mg(2+) but not with K(+) and Na(+). The effect of pH on Cr(III) toxicity to barley root elongation could be explained by H(+) competition with Cr(3+) bound to a biotic ligand (BL) as well as by the concomitant toxicity of CrOH(2+) in solution culture. Stability constants were obtained for the binding of Cr(3+), CrOH(2+), Ca(2+), Mg(2+) and H(+) with binding ligand: log KCrBL 7.34, log KCrOHBL 5.35, log KCaBL 2.64, log KMgBL 2.98, and log KHBL 4.74. On the basis of those estimated parameters, a BLM was successfully developed to predict Cr(III) toxicity to barley root elongation as a function of solution characteristics. PMID- 25119270 TI - Heterogeneous reactions of particulate matter-bound PAHs and NPAHs with NO3/N2O5, OH radicals, and O3 under simulated long-range atmospheric transport conditions: reactivity and mutagenicity. AB - The heterogeneous reactions of ambient particulate matter (PM)-bound polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs (NPAHs) with NO3/N2O5, OH radicals, and O3 were studied in a laboratory photochemical chamber. Ambient PM2.5 and PM10 samples were collected from Beijing, China, and Riverside, California, and exposed under simulated atmospheric long-range transport conditions for O3 and OH and NO3 radicals. Changes in the masses of 23 PAHs and 20 NPAHs, as well as the direct and indirect-acting mutagenicity of the PM (determined using the Salmonella mutagenicity assay with TA98 strain), were measured prior to and after exposure to NO3/N2O5, OH radicals, and O3. In general, O3 exposure resulted in the highest relative degradation of PM-bound PAHs with more than four rings (benzo[a]pyrene was degraded equally well by O3 and NO3/N2O5). However, NPAHs were most effectively formed during the Beijing PM exposure to NO3/N2O5. In ambient air, 2-nitrofluoranthene (2-NF) is formed from the gas-phase NO3 radical- and OH radical-initiated reactions of fluoranthene, and 2-nitropyrene (2-NP) is formed from the gas-phase OH radical-initiated reaction of pyrene. There was no formation of 2-NF or 2-NP in any of the heterogeneous exposures, suggesting that gas-phase formation of NPAHs did not play an important role during chamber exposures. Exposure of Beijing PM to NO3/N2O5 resulted in an increase in direct acting mutagenic activity which was associated with the formation of mutagenic NPAHs. No NPAH formation was observed in any of the exposures of the Riverside PM. This was likely due to the accumulation of atmospheric degradation products from gas-phase reactions of volatile species onto the surface of PM collected in Riverside prior to exposure in the chamber, thus decreasing the availability of PAHs for reaction. PMID- 25119273 TI - Acute orthostatic headache and diplopia due to a spinal subarachnoid haemorrhage. PMID- 25119274 TI - Hemidystonia caused by frontal cortical infarction. PMID- 25119275 TI - Mercury (Hg) in fish consumed by the local population of the Jaguaribe River lower basin, Northeast Brazil. AB - The knowledge of Hg concentrations in fish is of considerable interest since these organisms are a major source of protein to coastal human populations and fishing communities. The main source of human exposure to Hg contamination occurs through the consumption of fish. In this paper, we compare Hg concentration in 13 fish species from Jaguaribe River lower basin and an adjacent coastal region in the northeastern coast of Brazil. We sampled fish from three stretches of the river: fluvial, estuarine, and marine regions. We tested the hypothesis that Hg concentration in muscle tissue vary according to species, location, and trophic level. Significant differences were observed among species and trophic level, but these could not be observed among the regions studied. As expected, the highest concentrations were observed in carnivorous fish (5.6-107.5; 26.9 +/- 18.8 ng g( 1)). Hg concentrations observed in this study are similar to those observed in regions of low environmental contamination. We estimated Hg intake to vary between 0.02 and 0.22 ng Hg kg body weight(-1) week(-1), for the average body weight of 56.7 kg, which was considered as low exposure and therefore, a low risk to consumers of fish from the regions studied. PMID- 25119276 TI - Simultaneously degradation of 2,4-dichlorophenol and EDTA in aqueous solution by the bimetallic Cu-Fe/O2 system. AB - Oxidative degradation of aqueous organic contaminants 2,4-dichlorophenol (2,4 DCP) using ethylenediaminetetraacetic acid (EDTA)-enhanced bimetallic Cu-Fe system in the presence of dissolved oxygen was investigated. The proposed process was applied for the pH range of 3~7 with the degradation efficiency of 2,4-DCP and EDTA varying within 10 %, and achieved at 100 % degradation of 40 mg L(-1) 2,4-DCP in 1 h, at the initial pH of 3, 25 g L(-1) of bimetallic Fe-Cu powder (WCu/WFe = 0.01289) and initial EDTA of 0.57 mM. However, the removal efficiency of 2,4-DCP in control tests were 7.52 % (Cu-Fe/O2 system) and 84.32 % (EDTA enhanced Fe/O2 process), respectively, after 3 h, reaction. The proposed main mechanism, involves the in situ generation of H2O2 by the electron transfer from Fe(0) to O2 which was enhanced by ethylenediaminetetraacetic acid (EDTA), and the in situ generation of .OH via advanced oxidation reaction. Accordingly, 2,4-DCP was attacked by .OH to achieve complete dechlorination and low molecular weight organic acids, even mineralized. Systematic studies on the effects of initial EDTA and 2,4-DCP concentration, Cu-Fe dosing, Cu content, and pH revealed that these effects need to be optimized to avoid the excessive consumption of .OH and new EDTA and heavy metal Cu pollution. PMID- 25119277 TI - Insights into community-based discrimination of water quality status using an annual pool of phytoplankton in mid-subtropical canal systems. AB - With rapid response to environmental changes, phytoplankton communities have been used as a favorable bioindicator to evaluate environmental stress and anthropogenic impacts in aquatic ecosystems. The feasibility for their community based bioassessment was studied in a mid-subtropical canal (Tiesha River), southern China, during a 1-year cycle (November 2009-December 2010). Samples were monthly collected at four sampling stations within a contamination gradient. Environmental variables, such as water temperature, dissolved oxygen (DO), chemical oxygen demand (COD), biological oxygen demand (BOD5), total phosphorus (TP), and total nitrogen (TN), were measured synchronously for comparison with biotic parameters. The phytoplankton community structures showed a significant difference among four stations. The spatial variation in abundance was significantly correlated with the changes in environmental variables, especially TN, TP, and COD. Four dominant species (Aulacoseira granulata, Leptocylindrus danicus, Oscillatoria tenuis, and Radiococcus nimbatus) were significantly correlated with nutrients, while the species richness index represented a significant correlation with BOD5. The phytoplankton-based Saprobien indices could not reveal the spatial variation in water quality status although may reflect water pollution levels (from beta- to alpha-mesosaprobic zone) in the canal system. It is suggested that phytoplankton communities might be used as a potentially robust bioindicator for discriminating environmental quality status in mid-tropical canal systems. PMID- 25119278 TI - The minimum detectable difference (MDD) and the interpretation of treatment related effects of pesticides in experimental ecosystems. AB - In the European registration procedure for pesticides, microcosm and mesocosm studies are the highest aquatic experimental tier to assess their environmental effects. Evaluations of microcosm/mesocosm studies rely heavily on no observed effect concentrations (NOECs) calculated for different population-level endpoints. Ideally, a power analysis should be reported for the concentration response relationships underlying these NOECs, as well as for measurement endpoints for which significant effects cannot be demonstrated. An indication of this statistical power can be provided a posteriori by calculated minimum detectable differences (MDDs). The MDD defines the difference between the means of a treatment and the control that must exist to detect a statistically significant effect. The aim of this paper is to expand on the Aquatic Guidance Document recently published by the European Food Safety Authority (EFSA) and to propose a procedure to report and evaluate NOECs and related MDDs in a harmonised way. In addition, decision schemes are provided on how MDDs can be used to assess the reliability of microcosm/mesocosm studies and for the derivation of effect classes used to derive regulatory acceptable concentrations. Furthermore, examples are presented to show how MDDs can be reduced by optimising experimental design and sampling techniques. PMID- 25119279 TI - Root morphological responses of three hot pepper cultivars to Cd exposure and their correlations with Cd accumulation. AB - Cultivars of hot pepper (Capsicum annuum L.) differ widely in their fruit cadmium (Cd) concentrations. Previously, we suggested that low-Cd cultivars are better able to prevent the translocation of Cd from roots to aboveground parts, but the corresponding mechanisms are still unknown. In this study, we aimed to improve understanding of the root morphological characteristics of the mechanisms involved in two low-Cd and a high-Cd cultivar. Seedlings were grown in nutrient solutions containing 0 (control), 2, and 10 MUM Cd for 20 days, and Cd contents for the three cultivars were compared with changes in root morphology. The total root length (RL), root surface area (SA), number of root tips (RT), and specific root length (SRL) of all cultivars were decreased significantly by the 10 MUM Cd treatment with the exception of the SA in JFZ, which showed no obvious change. For each cultivar, the 10 MUM Cd treatment decreased significantly RL and SA specifically in roots with diameters (RD) of RD <= 0.2 mm or 0.2 mm < RD <= 0.4 mm, and increased significantly RL and SA specifically in roots with diameters of 0.6 mm < RD <= 0.8 mm. Hot pepper cultivars differ greatly in Cd accumulation and root morphology. In the 10 MUM Cd treatment, root volume (RV), SA, and RT of all cultivars were negatively correlated with Cd concentration and amount in roots. However, RL, SA, RV, and RT of all cultivars were positively correlated with Cd concentration and amount in shoots, and translocation rate of Cd. The two low-Cd cultivars of hot pepper had less root tips, shorter root length, and smaller root surface area than the high-Cd cultivar in 10 MUM Cd treatment, which may play a vital role in reducing root-to-shoot Cd translocation. PMID- 25119280 TI - How do two giant panda populations adapt to their habitats in the Qinling and Qionglai Mountains, China. AB - The spatial separation of the Qinling Mountains from the western mountains has caused morphological and genetic distinctions of giant pandas. Could this separation also cause the pandas' behavior change? In this research, we focused on the pandas' movement pattern and selected two wild panda groups in Foping and Wolong Nature Reserves (NR) to represent the populations in the Qinling and Qionglai Mountains, respectively. We hypothesized that the Qinling pandas have developed a different seasonal movement pattern compared with the pandas in the western mountains. We analyzed the radio tracking data from two NRs by using GIS. Our results showed the following significant differences: (1) The Foping pandas live most of the year in the low elevation areas and move higher during June and remain through August while the Wolong pandas live most of the year in the high elevation areas and move lower in April and stay through June; (2) Comparing their low and high elevational areas shows the distinct spatial patterns between reserves, forming two obviously separated clusters in Foping but a single-compact cluster in Wolong; (3) Foping pandas move an average of 425 m +/- 147 s.d. daily, while Wolong pandas move an average of 550 m +/- 343 s.d. daily; and (4) Three habitat factors (i.e., terrain, temperature, and bamboo nutrient) were taken as the driving forces and analyzed, and they showed a strong support explanation to these different movement behaviors of pandas in two NRs. Our findings have important implications for management, for instance, it needs to be careful considering the behavior difference of the pandas when reintroducing them to the wild. PMID- 24839579 TI - Greetings from the editor-in-chief. PMID- 24839580 TI - The Korea National Health and Nutrition Examination Survey (KNHANES): current status and challenges. PMID- 25055010 TI - WHO Western Pacific regional action plan for the prevention and control of NCDs (2014-2020). PMID- 24904754 TI - T cell immunosenescence, hypertension, and arterial stiffness. PMID- 25119285 TI - NHC-AuCl/selectfluor: a highly efficient catalytic system for carbene-transfer reactions. AB - The combination of NHC-gold complex and Selectfluor has been found to be a highly efficient catalyst system for carbene-transfer reactions, with a turnover number (TON) up to 990000 and a turnover frequency (TOF) up to 82500 h(-1). PMID- 25119286 TI - Optical modulation of waveguiding in spiropyran-functionalized polydiacetylene microtube. AB - Optical modulation of waveguiding and logic operations play significant roles in highly integrated optical communication components, optical computing, and photonic circuits. Herein, we designed and synthesized spiropyran-functionalized polydiacetylene (SFPDA) microtubes, and realized reversible optical modulation of waveguiding in SFPDA microtubes through fluorescence resonance energy transfer (FRET) between the PDA matrix and spiropyran in open merocyanine (MC) form within the surface of the microtubes. Because of the reversible isomerization characteristics of spiropyran units, we have realized resettable, multireadout logic system that includes OR and INHIBIT logic operations in SFPDA microtube. PMID- 25119287 TI - Novel one-, two-, and three-dimensional selenidostannates templated by iron(II) complex cation. AB - The novel iron selenidostannates [Fe(bipy)3]Sn4Se9.2H2O (1) and [Fe(bipy)3]2[Sn3Se7]2.bipy.2H2O (2) (bipy = bipyridine) were prepared by the reactions of Sn, Se, FeCl2.4H2O, bipy, and dien with/without KSCN under hydrothermal conditions (dien = diethylenetriamine). In 1, four SnSe5 units condense via edge sharing to form the novel 3-D framework selenidostannate (infinity)3[Sn4Se92-] containing an interpenetrating channel system. The [Fe(bipy)3]2+ cations are accommodated in the different channels according to the conformation of the [Fe(bipy)3]2+ cation. In 2, three SnSe5 units share edges to form a 2-D (infinity)2[Sn3Se72-] layered anion, while two SnSe5 units and one SnSe4 unit are connected via edge sharing, forming a 1-D (infinity)1[Sn3Se72-] chainlike anion. The (infinity)1[Sn3Se72-], [Fe(bipy)3]2+, bipy, and H2O species are embedded between the (infinity)2[Sn3Se72-] layers. 2 is the first example of a selenidostannate constructed by both (infinity)2[Sn3Se72-]and (infinity)1[Sn3Se72-] anions. The coexistence of 1-D (infinity)1[Sn3Se72-] and 2 D (infinity)2[Sn3Se72-] anions in 2 might support the possible reaction mechanism that the (infinity)2[Sn3Se72-] anions are formed by condensation of the (infinity)1[Sn3Se72-] chains. 1 and 2 exhibit band gaps at 1.43 and 2.01 eV, respectively. PMID- 25119288 TI - Viscous friction between crystalline and amorphous phase of dragline silk. AB - The hierarchical structure of spider dragline silk is composed of two major constituents, the amorphous phase and crystalline units, and its mechanical response has been attributed to these prime constituents. Silk mechanics, however, might also be influenced by the resistance against sliding of these two phases relative to each other under load. We here used atomistic molecular dynamics (MD) simulations to obtain friction forces for the relative sliding of the amorphous phase and crystalline units of Araneus diadematus spider silk. We computed the coefficient of viscosity of this interface to be in the order of 10(2) Ns/m(2) by extrapolating our simulation data to the viscous limit. Interestingly, this value is two orders of magnitude smaller than the coefficient of viscosity within the amorphous phase. This suggests that sliding along a planar and homogeneous surface of straight polyalanine chains is much less hindered than within entangled disordered chains. Finally, in a simple finite element model, which is based on parameters determined from MD simulations including the newly deduced coefficient of viscosity, we assessed the frictional behavior between these two components for the experimental range of relative pulling velocities. We found that a perfectly relative horizontal motion has no significant resistance against sliding, however, slightly inclined loading causes measurable resistance. Our analysis paves the way towards a finite element model of silk fibers in which crystalline units can slide, move and rearrange themselves in the fiber during loading. PMID- 25119289 TI - Longitudinal hemodynamic measurements in swine heart failure using a fully implantable telemetry system. AB - Chronic monitoring of heart rate, blood pressure, and flow in conscious free roaming large animals can offer considerable opportunity to understand the progression of cardiovascular diseases and can test new diagnostics and therapeutics. The objective of this study was to demonstrate the feasibility of chronic, simultaneous measurement of several hemodynamic parameters (left ventricular pressure, systemic pressure, blood flow velocity, and heart rate) using a totally implantable multichannel telemetry system in swine heart failure models. Two solid-state blood pressure sensors were inserted in the left ventricle and the descending aorta for pressure measurements. Two Doppler probes were placed around the left anterior descending (LAD) and the brachiocephalic arteries for blood flow velocity measurements. Electrocardiographic (ECG) electrodes were attached to the surface of the left ventricle to monitor heart rate. The telemeter body was implanted in the right side of the abdomen under the skin for approximately 4 to 6 weeks. The animals were subjected to various heart failure models, including volume overload (A-V fistula, n = 3), pressure overload (aortic banding, n = 2) and dilated cardiomyopathy (pacing-induced tachycardia, n = 3). Longitudinal changes in hemodynamics were monitored during the progression of the disease. In the pacing-induced tachycardia animals, the systemic blood pressure progressively decreased within the first 2 weeks and returned to baseline levels thereafter. In the aortic banding animals, the pressure progressively increased during the development of the disease. The pressure in the A-V fistula animals only showed a small increase during the first week and remained stable thereafter. The results demonstrated the ability of this telemetry system of long-term, simultaneous monitoring of blood flow, pressure and heart rate in heart failure models, which may offer significant utility for understanding cardiovascular disease progression and treatment. PMID- 25119290 TI - ATF3 and extracellular matrix-related genes associated with the process of chronic obstructive pulmonary. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide and is proved to be the number three cause of death in globally. The objective of this study was to explore the molecular mechanism of the progression of COPD. METHODS: Using the GSE1650 affymetrix microarray data accessible from Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between 18 COPD samples and 12 normal samples, followed by the GO / KEGG pathway analysis and gene interaction networks analysis of the DEGs. Our study identified 134 DEGs which involved in regulation of immune response, vesicle transport system, growth regulator and extracellular matrix (ECM)-related pathways. RESULTS: Gene interaction networks analysis showed that the sub-network involved by activating transcription factor-3 (ATF3) was the most significant sub-network in gene interaction networks. Furthermore, the investigation of extracellular matrix-related genes showed that genes like collagen and insulin-like growth factor binding protein could clearly distinguish the COPD and normal control. CONCLUSIONS: The genes regulated by ATF3 transcriptional activator as well as ECM-related genes may play an important role in the process of COPD. Our study provides a comprehensive bioinformatics analysis of genes and pathways which may be involved in the progression of COPD. PMID- 25119291 TI - Feasibility of using the nasal route for linear endobronchial ultrasound. AB - PURPOSE: Linear endobronchial ultrasound (EBUS) is a safe and accurate diagnostic test for mediastinal adenopathy. Its feasibility through the nasal route has not been reported. The objective of this study was to document the feasibility of linear EBUS using the nasal route and compare its accuracy and safety with the oral route. METHODS: A retrospective analysis of consecutive subjects who underwent an EBUS procedure under conscious sedation at our center was conducted. Nasal insertion of the bronchoscope was attempted in all subjects; the oral route was used in case of failed nasal insertion. Characteristics of the procedure and the diagnostic accuracy of EBUS were compared between the two insertion routes. RESULTS: From May to October 2012, 209 subjects underwent an EBUS. Complete data were available for 196 subjects. Nasal insertion of the EBUS bronchoscope was possible in 73.5 %. There was no difference between the two insertion routes in the location and number of stations sampled per subject. Procedure duration and complications (epistaxis, bronchial bleeding, desaturation, and pneumothorax) were similar between the two groups (2.1 % for nasal group vs 1.9 % for oral group). Minor epistaxis occurred in one subject in the nasal group. Comparing the nasal and oral groups, rates of adequate specimens were similar (90.5 vs 88.9 %, respectively; p = 0.68), and proportions of diagnostic specimens were not statistically different (51.4 vs 42.3 %, respectively; p = 0.26). CONCLUSION: Linear EBUS can be performed safely and with high accuracy via the nasal route. Controlled studies are required to determine which insertion route provides best patient comfort. PMID- 25119292 TI - Service, training and outreach--the EARS Inc. Model for a self sustainable hearing program in action. AB - PURPOSE: EARS Inc. is a faith based not-for-profit organization established in 1998. As an organization, it has consistently maintained a goal to provide both short-term and long-term projects in low and middle income countries. One specific project undertaken by EARS Inc involved developing a hearing health program in the Dominican Republic. METHODS: This article is a review of the challenges and successes encountered on the road to establishing improved access and affordability of hearing aid technology for the hearing impaired in Domincan Republic. RESULTS: Despite the challenges, after 12 years of local programming, the hearing health services in the Dominican Republic were successfully implemented. The development of these services included the simultaneous development of a training program, earmould laboratory, hearing aid repair services as well as calibration services and sales of batteries and accessories. CONCLUSIONS: As demonstrated in this review, it is possible to develop sustainable and comprehensive diagnostic and rehabilitation hearing services in a developing country. It is clear that training, equipping and empowering local staffs are instrumental to the success of the program. IMPLICATIONS FOR REHABILITATION: A good hearing aid fitting is more than supplying technology. Patient education and the clinician fitting the hearing aid are important. Access to follow-up services including battery supplies, hearing aid adjustments and hearing aid repairs is essential for a hearing aid fitting program in low and middle income countries to be sustainable. Check the WHO guidelines for hearing aid provision in developing countries when planning a program. When working in a country, co-ordinate with local professionals involved in hearing health where available. PMID- 25119293 TI - Developing self-sustainable hearing centers in the developing world--case study of EARs Inc project in Dominican Republic. AB - PURPOSE: This paper presents the case study of the project EARS Ind developed in the Dominican Republic (DR) with the purpose of increasing access and affordability of hearing aid technology for the hearing impaired. This case study demonstrates how a program can fit hearing aids to patients with hearing impairments can be developed in low and middle income countries. METHODS: The project planning documents and project statistics and reports were reviewed. A questionnaire and follow-up interviews were used to gain a clear understanding of the situation in the EARS Inc. DR hearing aid project. RESULTS: The case study is presented of the development and services in the DR with a particular focus on the choices made in regard to hearing aid services including manufacturer choices, procurement, distribution, pricing and service delivery. The development of these services included the simultaneous development of a training program, ear mould laboratory, hearing aid repair services, also sales of batteries and accessories as well as the development of calibration services. CONCLUSIONS: The development of comprehensive diagnostic and rehabilitation services requires equipping and training local staff. IMPLICATIONS FOR REHABILITATION: A good hearing aid fitting is more than technology--patient education and the clinician fitting the hearing aid are important. Access to follow-up services including battery supplies, hearing aid adjustments and hearing aid repairs is essential to any hearing aid fitting program in low and middle income countries. Check the WHO guidelines for hearing aid provision in developing countries when planning a program. When working in a country co-ordinate with local professional involved in hearing health where available. PMID- 25119294 TI - Cell oxidation-reduction imbalance after modulated radiofrequency radiation. AB - Aim of this study was to evaluate an influence of modulated radiofrequency field (RF) of 1800 MHz, strength of 30 V/m on oxidation-reduction processes within the cell. The assigned RF field was generated within Gigahertz Transversal Electromagnetic Mode cell equipped by signal generator, modulator, and amplifier. Cell line V79, was irradiated for 10, 30, and 60 min, specific absorption rate was calculated to be 1.6 W/kg. Cell metabolic activity and viability was determined by MTT assay. In order to define total protein content, colorimetric method was used. Concentration of oxidised proteins was evaluated by enzyme linked immunosorbent assay. Reactive oxygen species (ROS) marked with fluorescent probe 2',7'-dichlorofluorescin diacetate were measured by means of plate reader device. In comparison with control cell samples, metabolic activity and total protein content in exposed cells did not differ significantly. Concentrations of carbonyl derivates, a product of protein oxidation, insignificantly but continuously increase with duration of exposure. In exposed samples, ROS level significantly (p < 0.05) increased after 10 min of exposure. Decrease in ROS level was observed after 30-min treatment indicating antioxidant defence mechanism activation. In conclusion, under the given laboratory conditions, modulated RF radiation might cause impairment in cell oxidation-reduction equilibrium within the growing cells. PMID- 25119296 TI - Regioselective synthesis of enones via a titanium-promoted coupling of unsymmetrical alkynes with weinreb amides. AB - A modular titanium-promoted coupling of unsymmetrical internal alkynes with Weinreb amides is described. The coupling reaction takes place at room temperature and affords E-trisubstituted enones in moderate to good yields with high levels of regioselectivity. The system shows moderate chemoselectivity. PMID- 25119295 TI - A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV. AB - Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder often characterized by severe neurodevelopmental abnormalities and neuro-retinal degeneration. Mutations in the TRPML1 gene are causative for MLIV. We used lead optimization strategies to identify--and MLIV patient fibroblasts to test--small molecule activators for their potential to restore TRPML1 mutant channel function. Using the whole-lysosome planar patch-clamp technique, we found that activation of MLIV mutant isoforms by the endogenous ligand PI(3,5)P2 is strongly reduced, while activity can be increased using synthetic ligands. We also found that the F465L mutation renders TRPML1 pH insensitive, while F408Delta impacts synthetic ligand binding. Trafficking defects and accumulation of zinc in lysosomes of MLIV mutant fibroblasts can be rescued by the small molecule treatment. Collectively, our data demonstrate that small molecules can be used to restore channel function and rescue disease associated abnormalities in patient cells expressing specific MLIV point mutations. PMID- 25119297 TI - Pneumocystis jirovecii pneumonia under everolimus in two patients with metastatic pancreatic neuroendocrine tumors. AB - BACKGROUND: Everolimus, an mTOR inhibitor with immunosuppressive properties, is used in several types of advanced tumors. Materials and METHODS: We describe the first two cases of Pneumocystis jirovecii pneumonia in patients given everolimus for metastatic pancreatic neuroendocrine tumors. RESULTS: The first patient presented with respiratory symptoms in the context of grade 4 lymphopenia 2 weeks after starting everolimus; the diagnosis of Pneumocystis jirovecii pneumonia was made post-mortem. After suspecting everolimus-related interstitial pneumonitis in the second patient, Pneumocystis jirovecii was detected, and cotrimoxazole therapy led to a favorable outcome. CONCLUSION: Everolimus may induce pneumonitis, lymphopenia and opportunistic infections. The time from treatment initiation to opportunistic infection may be short. Risk factors in oncology deserve further identification in order to start prophylaxis without delay. PMID- 25119299 TI - Fundamental study of a real-time occupational dosimetry system for interventional radiology staff. AB - Real-time monitoring of the radiation doses received by interventional radiology (IR) staff has become highly desirable. However, occupational doses are rarely measured in real time, due to the lack of a feasible method for use in IR. Recently, the i2 system by RaySafeTM has been introduced to measure occupational exposure in IR in real time. The i2 system consists of several personal dosimeters (PDs) and a base station with a display and computer interfacing. We evaluated the fundamental performance (dose linearity, dose-rate dependence, angular dependence, batch uniformity and reproducibility) of the i2 system. The dose linearity of the i2 was excellent (R(2) = 1.00) The i2 exhibited slight dose rate dependence (~20%) at very high dose rates (250 mGy h(-1)). Little angular dependence (within 20%) was observed between 0 degrees and +/-45 degrees , in either the vertical or horizontal direction. We also found that the PD was highly sensitive (about 200%) at angles behind it, e.g. 180 degrees . However, this backscattered radiation is not a problem, in general, due to the placement of the i2 sensor (PD) on the lead apron. We conclude that the i2 system facilitates accurate real-time monitoring and management of occupational doses during IR. PMID- 25119298 TI - A proteinaceous fraction of wheat bran may interfere in the attachment of enterotoxigenic E. coli K88 (F4+) to porcine epithelial cells. AB - Wheat bran (WB) from Triticum aestivum has many beneficial effects on human health. To the best of our knowledge, very little has been published about its ability to prevent pathogenic bacterial adhesion in the intestine. Here, a WB extract was fractionated using different strategies, and the obtained fractions were tested in different in vitro methodologies to evaluate their interference in the attachment of enterotoxigenic Escherichia coli (ETEC) K88 to intestinal porcine epithelial cells (IPEC-J2) with the aim of identifying the putative anti adhesive molecules. It was found that a proteinaceous compound in the >300-kDa fraction mediates the recognition of ETEC K88 to IPEC-J2. Further fractionation of the >300-kDa sample by size-exclusion chromatography showed several proteins below 90 kDa, suggesting that the target protein belongs to a high-molecular weight (MW) multi-component protein complex. The identification of some relevant excised bands was performed by mass spectrometry (MS) and mostly revealed the presence of various protease inhibitors (PIs) of low MW: Serpin-Z2B, Class II chitinase, endogenous alpha-amylase/subtilisin inhibitor and alpha amylase/trypsin inhibitor CM3. Furthermore, an incubation of the WB extract with ETEC K88 allowed for the identification of a 7S storage protein globulin of wheat, Globulin 3 of 66 kDa, which may be one of the most firmly attached WB proteins to ETEC K88 cells. Further studies should be performed to gain an understanding of the molecular recognition of the blocking process that takes place. All gathered information can eventually pave the way for the development of novel anti-adhesion therapeutic agents to prevent bacterial pathogenesis. PMID- 25119301 TI - An electrochemical immunosensor based on interdigitated array microelectrode for the detection of chlorpyrifos. AB - An electrochemical immunosensor based on interdigitated array microelectrodes (IDAMs) was developed for sensitive, specific and rapid detection of chlorpyrifos. Anti-chlorpyrifos monoclonal antibodies were orientedly immobilized onto the gold microelectrode surface through protein A. Chlorpyrifos were then captured by the immobilized antibody, resulting in an impedance change in the IDAMs surface. Electrochemical impedance spectroscopy was used in conjunction with the fabricated sensor to detect chlorpyrifos. Under optimum conditions, the impedance value change of chlorpyrifos was proportional to its concentrations in the range of 10(0)-10(5) ng/mL. The detection limit was found to be 0.014 ng/mL for chlorpyrifos. The proposed chlorpyrifos immunosensor could be used as a screening method in pesticide determination for the analysis of environmental, agricultural and pharmaceutical samples due to its rapidity, sensitivity and low cost. PMID- 25119302 TI - Epimorphin expression in a rat model of pulmonary hypoplasia associated with congenital diaphragmatic hernia. AB - PURPOSE: The pathogenesis of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) remains unclear. Interactions between the epithelium and surrounding mesenchyme play an important role in normal lung morphogenesis. Epimorphin, a stromal protein, plays a role in epithelial morphogenesis and lung branching, both of which are involved in pulmonary hypoplasia. In this study, we aimed to examine the relationship between epimorphin and pulmonary hypoplasia associated with CDH in an animal model. METHODS: Time-pregnant rats were exposed to nitrofen or vehicle on gestational day 9 (D9). Fetuses were harvested on D16 and D20, and were divided into control, hypoplastic lungs with CDH (CDH+), and hypoplastic lungs without CDH (CDH-). Both lungs of each fetus were removed and subjected to morphometric and molecular biologic analyses. Lung-to-body weight ratios were calculated. Pulmonary RNA was extracted, and relative mRNA level of epimorphin was determined by quantitative real-time PCR (qRT-PCR). Protein expression of epimorphin was investigated by Western blotting. RESULTS: In groups D16 and D20, lung-to-body weight ratios in subgroups CDH+ were significantly lower than those of controls and CDH-. The relative mRNA expression levels of epimorphin were significantly increased in both lungs in subgroup CDH+ compared with controls and CDH- on D16. Pulmonary epimorphin gene expression levels were significantly decreased in CDH+ group on D20 compared to controls. Western blotting confirmed the qRT-PCR results showing decreased pulmonary epimorphin protein expression in CDH+ hypoplastic lungs compared to controls on D20. CONCLUSION: Our study shows that there is an association between the epimorphin expression and pulmonary hypoplasia associated with CDH. Although the cause effect relationship is far from being established, epimorphin-related mechanisms have a more critical role in early (D16) developmental stage. PMID- 25119303 TI - "Spiral intestinal lenghtening and tailoring (SILT)" for a child with severely short bowel. AB - We report a child with post-surgical short bowel state who underwent bowel expansion followed by spiral intestinal lengthening and tailoring (SILT) at 10 months of age. Growth at 1-year follow-up is along the 15-25th centile on 82 % oral calories as normal diet and 18 % as parenteral nutrition, and he is passing 2-3 semisolid motions daily. SILT is a versatile technique for reconstructing dilated bowel towards improved propulsion and absorption, and has a role in the management of the short bowel state. PMID- 25119305 TI - Georg Buchner, Sigmund Freud and the "Schadelnerven" (cranial nerves) - research on the brain and soul in the 19th century. AB - BACKGROUND: One of the authors' encounter with one of Sigmund Freud's original works about the anatomy of the human brain stem and his interest in the scientist, anatomist, philosopher, writer and revolutionary Georg Buchner led to re-examination and review of the original writings of two major 19th century protagonists of brain anatomy research. The aim of the authors is to highlight the achievements of both Freud and Buchner in the field of comparative brain morphology. METHODS: The medical and philosophical publications of Georg Buchner were reviewed with reference to the historical-critical edition of his complete works and writings (the so-called Marburg edition). Evaluation of the neuroanatomical achievements of Sigmund Freud was based on a summary of his publications and also partially on his autobiographical writings. RESULTS: After careful review of their publications both Freud and Buchner should be acknowledged as brain scientists focusing particularly on comparative morphology. Both chose fish as the subject of their macroscopic (Buchner) and microscopic (Freud) neuroanatomical studies, and both cut across their own language and cultural space by continuing their work in France. In interpreting their findings both were influenced by their respective contemporary methodological schools of thought. Buchner became a soul scientist/psychologist by turning to the writing of literary texts, heralding the end of his idealistic and metaphysical interpretation of life. Likewise, Freud increasingly devoted himself to the destiny of man and his "conditio humana," eventually turning away from anatomical brain research. CONCLUSION: Review of the biographies and medical-scientific, as well as philosophical publications, of Georg Buchner and Sigmund Freud reveal striking parallels between the two researchers in addition to common insights that have generally been ignored or only marginally addressed in the past. Both should be appreciated and remembered as forerunners of today's neuroscientific community. PMID- 25119306 TI - [Rare cause of an abdominal emergency--case 6/2014]. AB - HISTORY AND ADMISSION FINDINGS: We report on a 58-year-old male patient with abdominal and right-sided flank pain, who presented with the picture of an acute abdominal emergency. INVESTIGATIONS: Laboratory tests revealed evidence of an inflammation and a hematuria. In the Doppler duplex ultrasound and computed tomography, chronic idiopathic periaortitis was diagnosed. The inflammatory fibrosing disease resulted in urine retention and rupture of the fornix of the right kidney. DIAGNOSIS, TREATMENT AND COURSE: After surgical implementation of an ureteral stent and initiation of immunosuppressive therapy, it came to an improvement of the symptoms. CONCLUSIONS: In the differential diagnosis of an acute abdominal emergency, diseases of the aorta should be taken into account. Especially in male patients with anatomical complications it is important to exclude an inflammatory-fibrosing disease. PMID- 25119307 TI - Identification of a novel HOG1 homologue from an industrial glycerol producer Candida glycerinogenes. AB - Candida glycerinogenes, a glycerol production industrial strain with hyperosmo adaptation can grow well in 15 % (w/v) NaCl or 55 % (w/v) glucose. To understand the osmo-adaptation mechanism in C. glycerinogenes, the mitogen-activated protein kinase HOG1 gene (CgHOG1), which plays an essential role in the yeast hyperosmotic response, was isolated by degenerate PCR and SEFA-Formed Adaptor PCR. The CgHOG1 gene was then transformed in Saccharomyces cerevisiae hog1Delta null mutant, which restored the recombination S. cerevisiae to the wild-type phenotype with osmo-adaptation. To further clarify the function of CgHOG1, the phosphorylation of CgHOG1 and transcription of the glycerol-3-phosphate dehydrogenase gene (GPD1) of the CgHOG1-harbouring S. cerevisiae mutant was detected, and found to be similar to that of wild-type S. cerevisiae. In addition, the recombination S. cerevisiae with CgHOG1 gene significantly accumulated intracellular glycerol when stressed with NaCl. PMID- 25119308 TI - Acid resistance contributes to the high-pressure carbon dioxide resistance of Escherichia coli K-12. AB - Effect of deletion of acid resistant genes of E. coli on the high-pressure carbon dioxide (HPC) resistance was investigated. Genes coding amino acid decarboxylases, such as lysine, arginine, and glutamate decarboxylase, were found to contribute to HPC resistance. Protonophore-treated cells showed hypersensitivity to HPC, confirming that HPC induced cytoplasm acidification and exerted severe damage on cells by intrusion of gaseous carbon dioxide into cytoplasm. PMID- 25119304 TI - The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's disease on recollection and familiarity: a meta-analytic review. AB - It is well established that healthy aging, amnestic Mild Cognitive Impairment (aMCI), and Alzheimer's Disease (AD) are associated with substantial declines in episodic memory. However, there is still debate as to how two forms of episodic memory - recollection and familiarity - are affected by healthy and pathological aging. To address this issue we conducted a meta-analytic review of the effect sizes reported in studies using remember/know (RK), receiver operating characteristic (ROC) and process dissociation (PD) methods to examine recollection and familiarity in healthy aging (25 published reports), aMCI (9 published reports), and AD (5 published reports). The results from the meta analysis revealed that healthy aging is associated with moderate-to-large recollection impairments. Familiarity was not impaired in studies using ROC or PD methods but was impaired in studies that used the RK procedure. aMCI was associated with large decreases in recollection whereas familiarity only tended to show a decrease in studies with a patient sample comprised of both single domain and multiple-domain aMCI patients. Lastly, AD was associated with large decreases in both recollection and familiarity. The results are consistent with neuroimaging evidence suggesting that the hippocampus is critical for recollection whereas familiarity is dependent on the integrity of the surrounding perirhinal cortex. Moreover, the results highlight the relevance of method selection when examining aging, and suggest that familiarity deficits might be a useful behavioral marker for identifying individuals that will develop dementia. PMID- 25119309 TI - Acanthamoeba T4, T5 and T11 isolated from mineral water bottles in southern Brazil. AB - Acanthamoeba is a protist potential pathogen, capable of causing a blinding keratitis in contact lens wearers and disseminated infection, leading to granulomatous amebic encephalitis in immunocompromised individuals. This amoeba is a ubiquitous organism that has been isolated from various domestic water systems, such as cooling towers and hospital water networks. The objective of this work was to investigate the presence of Acanthamoeba in mineral water bottles marketed in Porto Alegre, southern Brazil. Positive samples were further classified at the genotype level after sequencing the ASA.S1 region of 18S rDNA gene. Six of the eight isolates belonged to T5 genotype, one to T4 genotype, and one was T11. Several genotypes have been reported worldwide as causative of pathologies in humans, including genotypes T4, T5 and T11. Overall, the widespread distribution of potentially pathogenic Acanthamoeba strains in the studied source demands more awareness within the public and health professionals, because this pathogen is emerging as a risk for human health worldwide. PMID- 25119311 TI - Common and rare variants in the exons and regulatory regions of osteoporosis related genes improve osteoporotic fracture risk prediction. AB - CONTEXT: Osteoporotic fracture risk is highly heritable, but genome-wide association studies have explained only a small proportion of the heritability to date. Genetic data may improve prediction of fracture risk in osteopenic subjects and assist early intervention and management. OBJECTIVE: To detect common and rare variants in coding and regulatory regions related to osteoporosis-related traits, and to investigate whether genetic profiling improves the prediction of fracture risk. DESIGN AND SETTING: This cross-sectional study was conducted in three clinical units in Korea. PARTICIPANTS: Postmenopausal women with extreme phenotypes (n = 982) were used for the discovery set, and 3895 participants were used for the replication set. MAIN OUTCOME MEASURE: We performed targeted resequencing of 198 genes. Genetic risk scores from common variants (GRS-C) and from common and rare variants (GRS-T) were calculated. RESULTS: Nineteen common variants in 17 genes (of the discovered 34 functional variants in 26 genes) and 31 rare variants in five genes (of the discovered 87 functional variants in 15 genes) were associated with one or more osteoporosis-related traits. Accuracy of fracture risk classification was improved in the osteopenic patients by adding GRS-C to fracture risk assessment models (6.8%; P < .001) and was further improved by adding GRS-T (9.6%; P < .001). GRS-C improved classification accuracy for vertebral and nonvertebral fractures by 7.3% (P = .005) and 3.0% (P = .091), and GRS-T further improved accuracy by 10.2% (P < .001) and 4.9% (P = .008), respectively. CONCLUSIONS: Our results suggest that both common and rare functional variants may contribute to osteoporotic fracture and that adding genetic profiling data to current models could improve the prediction of fracture risk in an osteopenic individual. PMID- 25119310 TI - Exercise-induced irisin secretion is independent of age or fitness level and increased irisin may directly modulate muscle metabolism through AMPK activation. AB - CONTEXT: Irisin has been proposed to be a myokine mediating the effect of exercise on adipocyte browning. The physiology of irisin in humans is not completely understood. OBJECTIVE: To study the physiology of irisin in healthy individuals with different age and fitness levels and to explore the direct effects of irisin on muscle metabolism. DESIGN, SETTING, AND SUBJECTS: Treadmill exercise studies were conducted to measure circulating irisin at baseline and in response to exercise among old and young, physically active and sedentary individuals. Also, high- and moderate-intensity swimming was performed in adolescent men and women to study the effect of exercise intensity and the time course of irisin induction by acute bouts of exercise. Human myotubes were treated with recombinant irisin, and the effect on gene expression, cell signaling, and metabolism was examined. RESULTS: Baseline circulating irisin was lower in old (vs young) and physically active (vs sedentary) subjects. Despite differences in basal levels, the percentage increase of irisin by acute bouts of exercise was not related to age or fitness level. The time course study revealed that circulating irisin increased immediately after high-intensity interval exercise and declined 1 hour thereafter. In vitro experiments showed that irisin facilitates glucose and lipid metabolism in human muscle through AMP kinase phosphorylation. CONCLUSIONS: Despite the differences in basal irisin levels, exercise-induced irisin secretion is independent of age or fitness level. Increased irisin can directly modulate muscle metabolism through AMP kinase activation. PMID- 25119312 TI - Changes in bone mineral density in newly diagnosed testicular cancer patients after anticancer treatment. AB - CONTEXT: Patients with germ cell tumors (GCTs) have an excellent prognosis but are at risk for silent fractures. Data on bone mineral density (BMD) after anticancer treatment are scarce. OBJECTIVE: The objective of the study was BMD monitoring in GCT patients treated with or without chemotherapy. DESIGN: We prospectively studied 63 newly diagnosed GCT patients with a median age of 33 years (range 16-70 y) within 3 months of unilateral orchidectomy. Twenty-seven patients (42.9%) had no metastases. Thirty-six patients (57.1%) with metastatic disease received combination chemotherapy. SETTING: This study was conducted at the outpatient clinic of a single academic institution. INTERVENTIONS: We performed dual-energy X-ray absorptiometry scans and collected blood samples on a yearly basis, before and up to 5 years after anticancer treatment. MAIN OUTCOME MEASURES: Changes in total hip and lumbar spine BMD, serum concentrations of gonadal hormones, and bone turnover markers were measured. RESULTS: BMD remained normal in stage I patients. In patients with metastatic disease, a significant decrease in lumbar spine BMD (-1.52%; P = .004) and total hip BMD (-2.05%; P < .0001) was observed 1 year after chemotherapy and remained stable thereafter for up to 5 years. There was no significant relationship between the observed decrease in BMD and gonadal status, vitamin D status, or cumulative dose of cisplatin or (antiemetic) corticosteroids. CONCLUSIONS: Metastatic GCT survivors demonstrate significant bone loss within the first year after curative combination chemotherapy, with no recovery up to 5 years after anticancer treatment. Whether this bone loss is associated with increased fracture risk and whether this could be prevented by bone modifying treatment remains to be established. PMID- 25119313 TI - Ethnic differences in insulin sensitivity, beta-cell function, and hepatic extraction between Japanese and Caucasians: a minimal model analysis. AB - CONTEXT: Ethnic differences have previously been reported for type 2 diabetes. OBJECTIVE: We aimed at assessing the potential differences between Caucasian and Japanese subjects ranging from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) and to type 2 diabetes. DESIGN: This was a cross-sectional study with oral glucose tolerance tests to assess beta-cell function, hepatic insulin extraction, and insulin sensitivity. PARTICIPANTS: PARTICIPANTS included 120 Japanese and 150 Caucasian subjects. MAIN OUTCOMES: Measures of beta-cell function, hepatic extraction, and insulin sensitivity were assessed using C peptide, glucose, and insulin minimal models. RESULTS: Basal beta-cell function (Phi(b)) was lower in Japanese compared with Caucasians (P < .01). In subjects with IGT, estimates of the dynamic (Phi(d)) and static (Phi(s)) beta-cell responsiveness were significantly lower in the Japanese compared with Caucasians (P < .05). In contrast, values of insulin action showed higher sensitivity in the Japanese IGT subjects. Hepatic extraction was similar in NGT and IGT groups but higher in Japanese type 2 diabetic subjects (P < .01). Despite differences in insulin sensitivity, beta-cell function, and hepatic extraction, the disposition indices were similar between the 2 ethnic groups at all glucose tolerance states. Furthermore, the overall insulin sensitivity and beta-cell responsiveness for all glucose tolerance states were similar in Japanese and Caucasians after accounting for differences in body mass index. CONCLUSION: Our study provides evidence for a similar ability of Japanese and Caucasians to compensate for increased insulin resistance. PMID- 25119314 TI - Aldosterone suppression on contralateral adrenal during adrenal vein sampling does not predict blood pressure response after adrenalectomy. AB - CONTEXT: Adrenal vein sampling (AVS) is the only reliable means to distinguish between aldosterone-producing adenoma and bilateral adrenal hyperplasia, the two most common subtypes of primary aldosteronism (PA). AVS protocols are not standardized and vary widely between centers. OBJECTIVE: The objective of the study was to retrospectively investigate whether the presence of contralateral adrenal (CL) suppression of aldosterone secretion was associated with improved postoperative outcomes in patients who underwent unilateral adrenalectomy for PA. SETTING: The study was carried out in eight different referral centers in Italy, Germany, and Japan. PATIENTS: From 585 consecutive AVS in patients with confirmed PA, 234 procedures met the inclusion criteria and were used for the subsequent analyses. RESULTS: Overall, 82% of patients displayed contralateral suppression. This percentage was significantly higher in ACTH stimulated compared with basal procedures (90% vs 77%). The CL ratio was inversely correlated with the aldosterone level at diagnosis and, among AVS parameters, with the lateralization index (P = .02 and P = .01, respectively). The absence of contralateral suppression was not associated with a lower rate of response to adrenalectomy in terms of both clinical and biochemical parameters, and patients with CL suppression underwent a significantly larger reduction in the aldosterone levels after adrenalectomy. CONCLUSIONS: For patients with lateralizing indices of greater than 4 (which comprised the great majority of subjects in this study), CL suppression should not be required to refer patients to adrenalectomy because it is not associated with a larger blood pressure reduction after surgery and might exclude patients from curative surgery. PMID- 25119317 TI - On the chemical behavior of C60 hosting H2O and other isoelectronic neutral molecules. AB - The density functional theory (DFT) was used to investigate the chemical behavior of C60 hosting neutral guest molecules (NGM). The deformed atoms in molecules (DAM) allowed identifying the regions of electron density depletion and accumulation. The studied NGM are CH4, NH3, H2O, and HF. Based on dipole moment and polarizabilities analyses it is predicted that the NGM@C60 should be more soluble in polar solvents than C60. The deformations on the surface electron density of the fullerenes explain this finding, which might be relevant for further applications of these systems. It was found that the intrinsic reactivity of studied NGM@C60 is only moderately higher than that of C60. This trend is supported by the global reactivity indexes and the frontier orbitals analyses. The free radical scavenging activity of the studied systems, via single electron transfer, was found to be strongly dependent on the chemical nature of the reacting free radical. The presence of the studied NGM inside the C60 influences only to some extent the reactivity of C60 toward free radicals. The distortion of the electron density on the C60 cage, caused by the NGM, is directly related to the electron withdrawing capacity of the later. PMID- 25119316 TI - Lenti-GDNF gene therapy protects against Alzheimer's disease-like neuropathology in 3xTg-AD mice and MC65 cells. AB - AIMS: Glial cell-derived neurotrophic factor (GDNF) is emerging as a potent neurotrophic factor with therapeutic potential against a range of neurodegenerative conditions including Alzheimer's disease (AD). We assayed the effects of GDNF treatment in AD experimental models through gene-therapy procedures. METHODS: Recombinant lentiviral vectors were used to overexpress GDNF gene in hippocampal astrocytes of 3xTg-AD mice in vivo, and also in the MC65 human neuroblastoma that conditionally overexpresses the 99-residue carboxyl terminal (C99) fragment of the amyloid precursor protein. RESULTS: After 6 months of overexpressing GDNF, 10-month-old 3xTg-AD mice showed preserved learning and memory, while their counterparts transduced with a green fluorescent protein vector showed cognitive loss. GDNF therapy did not significantly reduce amyloid and tau pathology, but rather, induced a potent upregulation of brain-derived neurotrophic factor that may act in concert with GDNF to protect neurons from atrophy and degeneration. MC65 cells overexpressing GDNF showed an abolishment of oxidative stress and cell death that was at least partially mediated by a reduced presence of intracellular C99 and derived amyloid beta oligomers. CONCLUSIONS: GDNF induced neuroprotection in the AD experimental models used. Lentiviral vectors engineered to overexpress GDNF showed to be safe and effective, both as a potential gene therapy and as a tool to uncover the mechanisms of GDNF neuroprotection, including cross talk between astrocytes and neurons in the injured brain. PMID- 25119315 TI - Integrative analysis of GWASs, human protein interaction, and gene expression identified gene modules associated with BMDs. AB - CONTEXT: To date, few systems genetics studies in the bone field have been performed. We designed our study from a systems-level perspective by integrating genome-wide association studies (GWASs), human protein-protein interaction (PPI) network, and gene expression to identify gene modules contributing to osteoporosis risk. METHODS: First we searched for modules significantly enriched with bone mineral density (BMD)-associated genes in human PPI network by using 2 large meta-analysis GWAS datasets through a dense module search algorithm. One included 7 individual GWAS samples (Meta7). The other was from the Genetic Factors for Osteoporosis Consortium (GEFOS2). One was assigned as a discovery dataset and the other as an evaluation dataset, and vice versa. RESULTS: In total, 42 modules and 129 modules were identified significantly in both Meta7 and GEFOS2 datasets for femoral neck and spine BMD, respectively. There were 3340 modules identified for hip BMD only in Meta7. As candidate modules, they were assessed for the biological relevance to BMD by gene set enrichment analysis in 2 expression profiles generated from circulating monocytes in subjects with low versus high BMD values. Interestingly, there were 2 modules significantly enriched in monocytes from the low BMD group in both gene expression datasets (nominal P value <.05). Two modules had 16 nonredundant genes. Functional enrichment analysis revealed that both modules were enriched for genes involved in Wnt receptor signaling and osteoblast differentiation. CONCLUSION: We highlighted 2 modules and novel genes playing important roles in the regulation of bone mass, providing important clues for therapeutic approaches for osteoporosis. PMID- 25119318 TI - Quantum dynamics study of H + DBr and D + HBr reaction. AB - Time-dependent quantum wave packet calculations have been performed for the H + DBr and D + HBr reaction using the recent diabatic potential energy surfaces. Reaction probabilities, integral cross sections, and rate constants are obtained. The results show that the isotopic effects have an influence on the nonadiabatic effect which is generally inversely proportional to the atom mass. The calculated rate constants are in good overall agreement with experimental values, indicating that the ab initio surfaces are accurate to describe the isotopic effects. PMID- 25119319 TI - A computational study of hydrogen bonds in intermolecular systems of high complexity: arachno-pentaborane(11)...Y with Y = O2 and N 2. AB - The interactions of arachno-B(5)H(11) with N(2) and O(2) were theoretically studied. In the B(5)H(11)...N(2) and B(5)H(11)...O(2) complexes, the terminal hydrogens of B(5)H(11) work as electron donors whereas the bridge ones as electron acceptors. The optimized structures and the corresponding harmonic vibration spectra were investigated through the MP2/aug-cc-pVDZ level of theory. In order to characterize the hydrogen bonds, the topological calculations inherent to the QTAIM protocol and MEP analysis were carried out. The NBO analyses were useful in the interpretation of the red-shifts and blue-shifts on the stretch frequencies of the proton donors, of course in agreement with the Bent rule for the chemical bonding as well as by the conceptions of hyperconjugation or hybridization. PMID- 25119322 TI - No lost opportunities in the emergency department. PMID- 25119321 TI - UK mental health provision is not up to scratch. PMID- 25119323 TI - Integrating psychological screening into reviews of patients with COPD. AB - BACKGROUND: People with chronic obstructive pulmonary disease (COPD) have a high prevalence of anxiety and depression, which can have an impact on their symptoms and the way they manage their condition. Intervention that takes psychological distress into account may lead to better outcomes than simple advice-giving. AIM: To explore the feasibility of integrating psychological screening and intervention into nurse-led reviews of patients with COPD. METHOD: Nurses were given training on a pathway developed for patients with COPD. This included screening for depression and anxiety and assessing their severity; providing self management education by means of a motivational approach; and offering pulmonary rehabilitation. RESULTS: The nurses' level of confidence increased following training. Patients were accepting of the screening process and felt more able and motivated to manage their condition after the intervention. Eleven of the 35 patients that took part in the study period had evidence of anxiety and/or depression. Out of a total of 16 patients eligible for pulmonary rehabilitation, 12 agreed to referral. Of these, three patients were seen by their GP, one was started on antidepressants, and one was referred to the psychology service. CONCLUSION: Training practice nurses to screen for depression and anxiety, and to offer self-management education using a motivational interviewing approach, increased the reported capability and motivation of patients with COPD to manage their condition. It may also improve the uptake of pulmonary rehabilitation. Use of this pathway does not place a burden on other care providers or greatly increase prescribing costs. PMID- 25119320 TI - Optimization of dual-energy subtraction chest radiography by use of a direct conversion flat-panel detector system. AB - We aimed to optimize the exposure conditions in the acquisition of soft-tissue images using dual-energy subtraction chest radiography with a direct-conversion flat-panel detector system. Two separate chest images were acquired at high- and low-energy exposures with standard or thick chest phantoms. The high-energy exposure was fixed at 120 kVp with the use of an auto-exposure control technique. For the low-energy exposure, the tube voltages and entrance surface doses ranged 40-80 kVp and 20-100 % of the dose required for high-energy exposure, respectively. Further, a repetitive processing algorithm was used for reduction of the image noise generated by the subtraction process. Seven radiology technicians ranked soft-tissue images, and these results were analyzed using the normalized-rank method. Images acquired at 60 kVp were of acceptable quality regardless of the entrance surface dose and phantom size. Using a repetitive processing algorithm, the minimum acceptable doses were reduced from 75 to 40 % for the standard phantom and to 50 % for the thick phantom. We determined that the optimum low-energy exposure was 60 kVp at 50 % of the dose required for the high-energy exposure. This allowed the simultaneous acquisition of standard radiographs and soft-tissue images at 1.5 times the dose required for a standard radiograph, which is significantly lower than the values reported previously. PMID- 25119324 TI - Arterialised earlobe capillary blood gases in the COPD population. AB - Arterialised ear lobe capillary blood (ELCB) gas sampling is a widely used clinical procedure undertaken across both primary and secondary care settings. The prevalence of this sampling method has grown among health professionals, coupled with a growing demand for domiciliary oxygen therapy in the UK, in particular for those who have chronic obstructive pulmonary disease (COPD). Research studies supporting arterialised ELCB gas sampling show inconsistencies in technique, and a survey of respiratory nurses' current practice demonstrated wider inconsistencies. In the absence of national clinical guidelines to direct this practice, and an acknowledged and accepted under-calculation of partial pressure of oxygen, this article investigates the sampling method used to obtain arterialised ELCB gas sampling and consequently questions its reliability in practice. PMID- 25119325 TI - Spiritual coping of older persons in Malta and Australia (part 2). AB - Part I presented the research methodology and the quantitative findings of this descriptive sequential explanatory study. Part 2 will discuss the qualitative findings that explain the impact of the use of spiritual coping strategies on institutionalised older persons. Participants were recruited from six institutions in Malta and Australia: four private homes (two in Australia, n=30; two in Malta, n=43) and two state residences in Malta (n=64). The residents (n=137; 103 women, 34 men), aged 72.8 years (mean) were all Roman Catholics, mobile and with a minimal residence of 6 months. The quantitative data (phase I) were collected by the Maltese version of the Spiritual Coping scale (SCS) ( Baldacchino and Buhagiar, 2003 ) while the qualitative data were collected through audiotaped face-to-face interviews (n=42) (phase II) and three focus groups (n=23) (phase III). The qualitative data generated three main themes, namely: self-empowerment through connectedness with God, self, others and nature; belongingness to the residence; and the finding of meaning and purpose in life or the perceived afterlife. Recommendations were made for integration of spirituality into nursing education and clinical practice; more frequent participation in the socio-religious activities at ward level; self-awareness exercises and support groups; and further crosscultural longitudinal studies. PMID- 25119326 TI - Importance of being flexible in nurse education. PMID- 25119327 TI - Decontamination methods for flexible nasal endoscopes. AB - A national survey was carried out to investigate the current UK practice for decontaminating flexible nasal endoscopes. A postal questionnaire was sent to Sisters in Charge of 200 ear, nose and throat (ENT) outpatient departments in the UK, with an overall response rate of 60.5%. Decontamination with chlorine dioxide wipes was the most favoured method, used in 58% of the hospitals that participated in this survey. Automated machines were also used in many places (34%). Only a few hospitals used flexible sheaths (7%). Many departments do not use a separate protocol for high-risk patients. PMID- 25119328 TI - Understanding the concept of the key worker: do focus groups help? AB - The concept of the 'key-worker role' within paediatric haematology and oncology services is recognised in the UK through inclusion in published policies and guidance. Such guidance originates from both statutory and voluntary sector organisations. Within the policy direction itself, references are made to both 'designated' and 'non-designated' key workers, and there remains ongoing confusion within the professional field about the exact nature of the process of 'key-working' and how this should operate. This confusion therefore also exists for parents, carers and service users. The project described here aimed to examine the concept of the key-worker role through consultation with users as part of local service development. Focus group discussion was identified as the methodology of choice. Careful planning and delivery ensured that meaningful data emerged. Active participation by those attending the focus group discussion was observed. The focus group was in two sessions, both of which were digitally recorded and transcribed, with contemporaneous notes taken. These were subjected to thematic analysis and clear themes emerged regarding the importance of terminology, communication, skill mix and the use of technology. This local project achieved greater clarity about how to develop the key-worker role to best meet the needs of users through highlighting the need to include both the key worker role, and the process of key-working. It is concluded that the use of focus groups is both a valid and valuable mechanism of consultation, as user consultation regarding service design and evaluation of care delivered is high on the wider agenda of the NHS. PMID- 25119329 TI - New registration process for overseas nurses. PMID- 25119330 TI - The Mental Capacity Act 2005: riding the storm of criticism. PMID- 25119331 TI - Written communication: from staff nurse to nurse consultant. Part 1: core principles. PMID- 25119332 TI - We should engage with the Code. PMID- 25119333 TI - Dosimetric evaluation of hybrid brass/stainless-steel apertures for proton therapy. AB - In passive scattering proton therapy, patient specific collimators (apertures) are used to laterally shape the proton beam, and compensators are employed to distally conform proton dose to the target. Brass is a commonly used material for apertures and recently a hybrid brass/stainless-steel (BR/SST) aperture design has been introduced to reduce treatment cost without clinical flow change. We measured stopping power and leakage dose for apertures made of stainless steel and brass in the Proton Therapy system. The linear stopping power ratios for stainless steel (type 304) and brass to water were calculated to be 5.46 and 5.51, respectively. Measured stopping power ratios of SST and BR were 5.51 +/- 0.04 and 5.56 +/- 0.08, respectively, which agrees with the calculated values within 1%. Leakage dose on the downstream surface of two slabs of O18 cm stainless steel apertures (total thickness of 6.5 cm) for the maximum available proton energy (235 MeV) was 1.283% +/- 0.004% of the prescription dose, and was smaller compared to the 1.358% +/- 0.005% leakage dose measured for existing brass apertures of identical physical dimensions. Therefore, the existing beam range limits for brass aperture slabs used at our institution with safety margin allowances for material composition and delivered beam range uncertainties can be safely applied for the new BR/SST aperture design. Potential range differences in the brass and stainless steel interface regions of the hybrid design were further investigated using EBT3 GafChromic film. Film dosimetry revealed no discernible range variations across the brass and stainless steel interface regions. Neutron dose to the patient from brass and stainless steel apertures was simulated using the Monte Carlo method. The results indicate that stainless steel produces similar patient neutron dose compared to brass. Material activation dose rates of stainless steel were measured over a period of 7 d after irradiation. The measurements showed that the proton induced SST activity is initially lower and also decays at a faster rate than that induced in brass, therefore requires no changes in radiation protection requirements on material disposals. The Monte Carlo simulation confirmed higher initial activity of brass than stainless steel shortly after irradiation. The hybrid BR/SST aperture design is suitable for clinical use to replace the current brass apertures for all clinically used proton ranges. The existing aperture disposal procedures also satisfy radiation protection requirements for the new hybrid type apertures. PMID- 25119334 TI - Transplantation of neural stem cells clonally derived from embryonic stem cells promotes recovery after murine spinal cord injury. AB - The pathology of spinal cord injury (SCI) makes it appropriate for cell-based therapies. Treatments using neural stem cells (NSCs) in animal models of SCI have shown positive outcomes, although uncertainty remains regarding the optimal cell source. Pluripotent cell sources such as embryonic stem cells (ESCs) provide a limitless supply of therapeutic cells. NSCs derived using embryoid bodies (EB) from ESCs have shown tumorigenic potential. Clonal neurosphere generation is an alternative method to generate safer and more clinically relevant NSCs without the use of an EB stage for use in cell-based therapies. We generated clonally derived definitive NSCs (dNSCs) from ESC. These cells were transplanted into a mouse thoracic SCI model. Embryonic stem cell-derived definitive neural stem cell (ES-dNSC)-transplanted mice were compared with controls using behavioral measures and histopathological analysis of tissue. In addition, the role of remyelination in injury recovery was investigated using transmission electron microscopy. The SCI group that received ES-dNSC transplantation showed significant improvements in locomotor function compared with controls in open field and gait analysis. The cell treatment group had a significant enhancement of spared neural tissue. Immunohistological assessments showed that dNSCs differentiated primarily to oligodendrocytes. These cells were shown to express myelin basic protein, associate with axons, and support nodal architecture as well as display proper compact, multilayer myelination in electron microscopic analysis. This study provides strong evidence that dNSCs clonally derived from pluripotent cells using the default pathway of neuralization improve motor function after SCI and enhance sparing of neural tissue, while remaining safe and clinically relevant. PMID- 25119335 TI - Elaidic, vaccenic, and rumenic acid status during pregnancy: association with maternal plasmatic LC-PUFAs and atopic manifestations in infants. AB - BACKGROUND: Few studies have explored whether fetal exposure to trans fatty acids (TFAs) influences the inception of atopic diseases. The aim of this study was to investigate the relationship between the concentration of specific TFAs (elaidic, vaccenic, and rumenic acids) in maternal plasma and the risk of developing atopic manifestations in the first year of life. METHODS: A subsample from a population based pregnancy cohort of the INMA Project was analyzed. Maternal intake of fatty acids was assessed by a food-frequency questionnaire (75.5% of the cohort). TFAs and n-3 and n-6 long-chain polyunsaturated fatty acids were measured in samples of plasmatic phospholipids at 12 wk of pregnancy. Information regarding eczema and wheeze in offspring was obtained through questionnaires at ages 6 and 14 mo. RESULTS: Elaidic acid correlated negatively with n-3 long-chain polyunsaturated fatty acids (total, eicosapentaenoic acid, and docosahexaenoic acid), and rumenic acid positively with both n-3 and n-6 long-chain polyunsaturated fatty acids in maternal plasma. Neither of these two fatty acids was associated with the risk of atopic eczema or wheeze in offspring in the first year of life. However, a higher vaccenic acid level was found to be linked to a lower risk of atopic eczema. CONCLUSION: High vaccenic acid concentrations in maternal plasma may protect offspring against atopic eczema in infancy. PMID- 25119337 TI - MBL2 gene polymorphisms increase the risk of adverse neurological outcome in preterm infants: a preliminary prospective study. AB - BACKGROUND: As described in animal models, the lectin-complement pathway is central to the propagation of ischemia-reperfusion injuries in many tissues, including the brain. Similarly, it might affect the genesis of brain damage in preterm infants. MBL2 gene single-nucleotide polymorphisms (SNPs), regulating mannose-binding lectin (MBL) serum levels, could predict the risk of adverse neurological outcome in these infants. METHODS: To evaluate the association between SNPs of the MBL2 gene and long-term neurological outcomes in preterm infants, 75 infants (gestational age (GA) <= 32 wk) were observed in a prospective longitudinal study and assessed by clinical and instrumental exams at 12 and 24 mo of corrected age (CA). They were genotyped for the promoter polymorphism -221 and for the exon-1 variant alleles (at codons 52, 54, and 57) of the MBL2 gene. RESULTS: The MBL2 exon-1 OO genotype was more frequent in children with an adverse neurological outcome (5/35; 7%) than in controls (0/40; 0%), P = 0.045. The risk of intraventricular hemorrhage in carriers of the genotype OO was marked, without reaching statistical significance (odds ratio: 8.67; 95% confidence interval: 0.87-86.06; P = 0.07). CONCLUSION: Preterm infants who are carriers of MBL2 exon-1 OO genotype are exposed to an increased risk of adverse neurological outcomes. PMID- 25119336 TI - One size will never fit all: the future of research in pediatric transfusion medicine. AB - There is concern at the National Heart, Lung, and Blood Institute (NHLBI) and among transfusion medicine specialists regarding the small number of investigators and studies in the field of pediatric transfusion medicine (PTM). Accordingly, the objective of this article is to provide a snapshot of the clinical and translational PTM research considered to be of high priority by pediatricians, neonatologists, and transfusion medicine specialists. Included is a targeted review of three research areas of importance: (i) transfusion strategies, (ii) short- and long-term clinical consequences, and (iii) transfusion-transmitted infectious diseases. The recommendations by PTM and transfusion medicine specialists represent opportunities and innovative strategies to execute translational research, observational studies, and clinical trials of high relevance to PTM. With the explosion of new biomedical knowledge and increasingly sophisticated methodologies over the past decade, this is an exciting time to consider transfusion medicine as a paradigm for addressing questions related to fields such as cell biology, immunology, neurodevelopment, outcomes research, and many others. Increased awareness of PTM as an important, fertile field and the promotion of accompanying opportunities will help establish PTM as a viable career option and advance basic and clinical investigation to improve the health and wellbeing of children. PMID- 25119338 TI - Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the role of the angiotensin type 2 receptor. AB - BACKGROUND: The angiotensin type-2 receptor (AT2R) opposes the vasoconstrictor actions of angiotensin II (AngII) mediated through the angiotensin type-1 receptor (AT1R). Renal AT2R levels are high during fetal life, but decrease significantly during postnatal maturation. To provide insight into the functional role of the AT2R in the kidney during postnatal development, we investigated the effects of AT2R antagonism on cardiovascular responses to AngII in young and adult male rats. METHODS: In anesthetized 3- and 6-wk-old male Sprague-Dawley rats, mean arterial pressure (MAP) and renal blood flow (RBF) were measured in response to AngII in the presence of vehicle treatment or AT2R blockade with PD123319. RESULTS: The pressor effect of AngII and associated reduction in RBF were significantly less in 3-wk- than 6-wk-old rats. AT2R blockade potentiated the reduction in RBF in response to AngII in 3-wk-old rats only. CONCLUSION: In young rats, the AT2R modulates the response to AngII, blunting renal vasoconstriction. This effect is attenuated with age in association with a developmental reduction in renal AT2R expression. These findings may have implications for the development of novel therapies that target the renin angiotensin system for the improvement of renal function in term and, in particular, preterm infants. PMID- 25119339 TI - Effects of iron supplements and perinatal factors on fetal hemoglobin disappearance in LBW infants. AB - BACKGROUND: The homeostatic mechanisms of iron metabolism and erythropoiesis in infants are unclear. Infants synthesize both fetal hemoglobin (HbF) and adult hemoglobin (HbA), and it is not known how the hemoglobin switch is regulated. We hypothesized that iron supplements to infants affect the disappearance of HbF. METHODS: We randomized 285 low-birth-weight infants (2,000-2,500 g) into three intervention groups receiving 0, 1, or 2 mg/kg/d of iron supplements from 6 wk to 6 mo of age. In the present secondary analysis, we analyzed iron status, total hemoglobin (Hb), and HbF fraction at 6 wk, 12 wk, and at 6 mo and calculated absolute levels of HbF. RESULTS: We observed dose-dependent increased levels of Hb in iron-supplemented groups at 6 mo of age. However, for absolute HbF concentration, there was no similar effect of intervention. Mean (SD) HbF was 81.2 (16.8), 37.0 (13.8), and 8.1 (5.6) g/l at 6 wk, 12 wk, and 6 mo, respectively, similar in all groups. In linear regression analyses, postconceptional age turned out as the major predictor of HbF, independent of gestational age at birth. CONCLUSION: Our hypothesis was rejected. Instead, we confirmed a close correlation to postconceptional age, supporting a genetically programmed switch, insensitive to most environmental factors including birth. PMID- 25119340 TI - Combination of intrauterine growth restriction and a high-fat diet impairs cholesterol elimination in rats. AB - BACKGROUND: Intrauterine growth restriction (IUGR) increases the risk of adult onset hypercholesterolemia. High-fat diet (HFD) consumption potentiates IUGR induced increased cholesterol. Cholesterol is converted to bile acids by Cyp7a1 in preparation for excretion. We hypothesized that IUGR rats fed a HFD will have increased cholesterol, decreased Cyp7a1 protein levels, and decreased bile acids compared to control rats fed a HFD. METHODS: At day 21, IUGR and control pups were placed on one of three diets: a regular chow or one of two HFDs containing 1% or 2% cholesterol. Cholesterol levels and hepatic Cyp7a1 protein levels were quantified a postnatal week 28. RESULTS: Both HFDs increased serum cholesterol levels in control rats, and HFD fed IUGR rats had further increased serum cholesterol up to 35-fold. Both HFDs increased hepatic cholesterol levels, and IUGR further increased hepatic cholesterol levels up to fivefold. IUGR decreased hepatic Cyp7a1 protein up to 75%, and hepatic bile acids up to 54%. CONCLUSION: IUGR increased cholesterol and bile acids and decreased Cyp7a1 protein in rats fed a HFD without changing food intake. These findings suggest that IUGR increases the vulnerability of HFD fed rats to hypercholesterolemia via decreased cholesterol conversion to bile acids. PMID- 25119342 TI - Psychometric Evaluation of the Wijma Delivery Expectancy/Experience Questionnaire Version B. AB - Examining the fear of delivery after childbirth is important. The authors' aim is to examine the overall psychometric quality of the Wijma Delivery Expectancy/Experience Questionnaire version B. Reliability and validity of the instrument were evaluated via reliability analysis, exploratory and confirmatory factor analyses, and multidimensional subscore estimation. A six-factor model was proposed to explain instrument results. Factors included concerns about labor pain, lack of positive behaviors, loneliness, lack of positive feelings, concerns about childbirth, and concerns about the baby. Researchers provide psychometric evidence about the quality of the questionnaire to measure fear of delivery after childbirth. PMID- 25119341 TI - Bystander activation and anti-tumor effects of CD8+ T cells following Interleukin 2 based immunotherapy is independent of CD4+ T cell help. AB - We have previously demonstrated that immunotherapy combining agonistic anti-CD40 and IL-2 (IT) results in synergistic anti-tumor effects. IT induces expansion of highly cytolytic, antigen-independent "bystander-activated" (CD8(+)CD44high) T cells displaying a CD25(-)NKG2D(+) phenotype in a cytokine dependent manner, which were responsible for the anti-tumor effects. While much attention has focused on CD4(+) T cell help for antigen-specific CD8(+) T cell expansion, little is known regarding the role of CD4(+) T cells in antigen-nonspecific bystander-memory CD8(+) T cell expansion. Utilizing CD4 deficient mouse models, we observed a significant expansion of bystander-memory T cells following IT which was similar to the non-CD4 depleted mice. Expanded bystander-memory CD8(+) T cells upregulated PD-1 in the absence of CD4(+) T cells which has been published as a hallmark of exhaustion and dysfunction in helpless CD8(+) T cells. Interestingly, compared to CD8(+) T cells from CD4 replete hosts, these bystander expanded cells displayed comparable (or enhanced) cytokine production, lytic ability, and in vivo anti-tumor effects suggesting no functional impairment or exhaustion and were enriched in an effector phenotype. There was no acceleration of the post-IT contraction phase of the bystander memory CD8(+) response in CD4 depleted mice. The response was independent of IL-21 signaling. These results suggest that, in contrast to antigen-specific CD8(+) T cell expansion, CD4(+) T cell help is not necessary for expansion and activation of antigen-nonspecific bystander-memory CD8(+) T cells following IT, but may play a role in regulating conversion of these cells from a central memory to effector phenotype. Additionally, the expression of PD-1 in this model appears to be a marker of effector function and not exhaustion. PMID- 25119344 TI - Response to Ansell et al. "Non-vitamin K antagonist oral anticoagulants (NOACs): no longer new or novel". (Thromb Haemost 2014; 112: 841). PMID- 25119345 TI - Site-specific immobilization of recombinant antibody fragments through material binding peptides for the sensitive detection of antigens in enzyme immunoassays. AB - The immobilization of an antibody is one of the key technologies that are used to enhance the sensitivity and efficiency of the detection of target molecules in immunodiagnosis and immunoseparation. Recombinant antibody fragments such as VHH, scFv and Fabs produced by microorganisms are the next generation of ligand antibodies as an alternative to conventional whole Abs due to a smaller size and the possibility of site-directed immobilization with uniform orientation and higher antigen-binding activity in the adsorptive state. For the achievement of site-directed immobilization, affinity peptides for a certain ligand molecule or solid support must be introduced to the recombinant antibody fragments. In this mini-review, immobilization technologies for the whole antibodies (whole Abs) and recombinant antibody fragments onto the surfaces of plastics are introduced. In particular, the focus here is on immobilization technologies of recombinant antibody fragments utilizing affinity peptide tags, which possesses strong binding affinity towards the ligand molecules. Furthermore, I introduced the material-binding peptides that are capable of direct recognition of the target materials. Preparation and immobilization strategies for recombinant antibody fragments linked to material-binding peptides (polystyrene-binding peptides (PS tags) and poly (methyl methacrylate)-binding peptide (PMMA-tag)) are the focus here, and are based on the enhancement of sensitivity and a reduction in the production costs of ligand antibodies. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. PMID- 25119343 TI - [Generalized anxiety disorder]. AB - Generalized anxiety disorder (GAD) is a prevalent mental condition with substantial impact on psychosocial functioning and quality of life. There is also an increased risk of comorbidity with several other mental and somatic diseases. Clinical symptomatology is characterized by excessive and uncontrollable worrying about distinct issues of daily living which is frequently associated with somatic symptoms of stress and anxiety. Neurobiological and psychological research provide evidence for alterations in (para) limbic areas, a disturbed monoaminergic transmission as well as for dysfunctional learning in the pathogenesis of GAD. Therefore, second generation antidepressants, such as selective serotonin reuptake inhibitors (SSRI), selective serotonin norepinephrine reuptake inhibitors (SSNRI), the calcium channel modulator pregabalin and cognitive behavioral therapy (CBT) are the first choice treatment options. Depending on symptom severity, patient preference and availability, both medication and CBT can be applied as monotherapy or in combination. PMID- 25119346 TI - Endovascular repair of arterial iliac vessel wall lesions with a self-expandable nitinol stent graft system. AB - OBJECTIVE: To assess the therapeutic outcome after endovascular repair of iliac arterial lesions (IALs) using a self-expandable Nitinol stent graft system. METHODS: Between July 2006 and March 2013, 16 patients (13 males, mean age: 68 years) with a self-expandable Nitinol stent graft. A total of 19 lesions were treated: nine true aneurysms, two anastomotic aneurysms, two dissections, one arteriovenous fistula, two type 1B endoleaks after endovascular aneurysm repair, one pseudoaneurysm, and two perforations after angioplasty. Pre-, intra-, and postinterventional imaging studies and the medical records were analyzed for technical and clinical success and postinterventional complications. RESULTS: The primary technical and clinical success rate was 81.3% (13/16 patients) and 75.0% (12/16), respectively. Two patients had technical failure due to persistent type 1A endoleak and another patient due to acute stent graft thrombosis. One patient showed severe stent graft kinking on the first postinterventional day. In two patients, a second intervention was performed. The secondary technical and clinical success rate was 87.5% (14/16) and 93.8% (15/16). The minor complication rate was 6.3% (patient with painful hematoma at the access site). The major complication rate was 6.3% (patient with ipsilateral deep vein thrombosis). During median follow-up of 22.4 months, an infection of the aneurysm sac in one patient and a stent graft thrombosis in another patient were observed. CONCLUSION: Endovascular repair of various IALs with a self-expandable Nitinol stent graft is safe and effective. PMID- 25119348 TI - The parasitic fauna of the European bison (Bison bonasus) (Linnaeus, 1758) and their impact on the conservation. Part 1. The summarising list of parasites noted. AB - During the current century, 88 species of parasites have been recorded in Bison bonasus. These are 22 species of protozoa (Trypanosoma wrublewskii, T. theileri, Giardia sp., Sarcocystis cruzi, S. hirsuta, S. hominis, S. fusiformis, Neospora caninum, Toxoplasma gondii, Cryptosporidium sp., Eimeria cylindrica, E. subspherica, E. bovis, E. zuernii, E. canadensis, E. ellipsoidalis, E. alabamensis, E. bukidnonensis, E. auburnensis, E. pellita, E. brasiliensis, Babesia divergens), 4 trematodes species (Dicrocoelium dendriticum, Fasciola hepatica, Parafasciolopsis fasciolaemorpha, Paramphistomum cervi), 4 cestodes species (Taenia hydatigena larvae, Moniezia benedeni, M. expansa, Moniezia sp.), 43 nematodes species (Bunostomum trigonocephalum, B. phlebotomum, Chabertia ovina, Oesophagostomum radiatum, O. venulosum, Dictyocaulus filaria, D.viviparus, Nematodirella alcidis, Nematodirus europaeus, N. helvetianus, N. roscidus, N. filicollis, N. spathiger, Cooperia oncophora, C. pectinata, C. punctata, C. surnabada, Haemonchus contortus, Mazamastrongylus dagestanicus, Ostertagia lyrata, O. ostertagi, O. antipini, O. leptospicularis, O. kolchida, O. circumcincta, O. trifurcata, Spiculopteragia boehmi, S. mathevossiani, S. asymmetrica, Trichostrongylus axei, T. askivali, T. capricola, T. vitrinus, Ashworthius sidemi, Onchocerca lienalis, O. gutturosa, Setaria labiatopapillosa, Gongylonema pulchrum, Thelazia gulosa, T. skrjabini, T. rhodesi, Aonchotheca bilobata, Trichuris ovis), 7 mites (Demodex bisonianus, D. bovis, Demodex sp., Chorioptes bovis, Psoroptes equi, P. ovis, Sarcoptes scabiei), 4 Ixodidae ticks (Ixodes ricinus, I. persulcatus, I. hexagonus, Dermacentor reticulatus), 1 Mallophaga species (Bisonicola sedecimdecembrii), 1 Anoplura (Haematopinus eurysternus), and 2 Hippoboscidae flies (Lipoptena cervi, Melophagus ovinus). There are few monoxenous parasites, many typical for cattle and many newly acquired from Cervidae. PMID- 25119347 TI - Artificially constructed quorum-sensing circuits are used for subtle control of bacterial population density. AB - Vibrio fischeri is a typical quorum-sensing bacterium for which lux box, luxR, and luxI have been identified as the key elements involved in quorum sensing. To decode the quorum-sensing mechanism, an artificially constructed cell-cell communication system has been built. In brief, the system expresses several programmed cell-death BioBricks and quorum-sensing genes driven by the promoters lux pR and PlacO-1 in Escherichia coli cells. Their transformation and expression was confirmed by gel electrophoresis and sequencing. To evaluate its performance, viable cell numbers at various time periods were investigated. Our results showed that bacteria expressing killer proteins corresponding to ribosome binding site efficiency of 0.07, 0.3, 0.6, or 1.0 successfully sensed each other in a population-dependent manner and communicated with each other to subtly control their population density. This was also validated using a proposed simple mathematical model. PMID- 25119349 TI - The parasitic fauna of the European bison (Bison bonasus) (Linnaeus, 1758) and their impact on the conservation. Part 2. The structure and changes over time. AB - During the last century the recorded parasite fauna of Bison bonasus includes 88 species. These are 22 species of protozoa, 4 trematode species, 4 cestode species, 43 nematode species, 7 mites, 4 Ixodidae ticks, 1 Mallophaga species, 1 Anoplura, and 2 Hippoboscidae flies. There are few monoxenous parasites, the majority of parasites are typical for other Bovidae and Cervidae species and many are newly acquired from Cervidae. This is an evident increased trend in the parasite species richness, in both the prevalence and intensity of infections, which is associated with the bison population size, host status (captive breeding or free-ranging) and the possibility of contact with other ruminant species. In light of the changes to parasite species richness during the last decades, special emphasis shall be given to new parasite species reported in European bison, their pathogenicity and potential implications for conservation. PMID- 25119350 TI - Larval helminths in the invasive American brine shrimp Artemia franciscana throughout its annual cycle. AB - One of the best examples of rapid displacement of native species by an invader is the eradication of native Artemia salina and A. parthenogenetica in the Mediterranean by the introduced American A. franciscana. Previous studies based on sampling from limited time periods suggest that the success of the American species as a competitor may be due partly to different parasite burden, since native Artemia spp. have high cestode infection rates regulating their density. The aim of this study is to test the hypothesis that the helminth infection in A. franciscana in its invasive range is low throughout its annual life cycle. Samples of A. franciscana were collected every second month from La Tapa saltern (Andalusia) during one year. Five helminth species were recorded: cestodes Flamingolepis liguloides, F. flamingo, Gynandrotaenia stammeri (all flamingo parasites), Eurycestus avoceti (a shorebird parasite) and larval spirurids of the Acuariinae (the first record of nematodes in Artemia). The overall infection rate was low, with total prevalence 5.9% and prevalence of individual parasite species between 0.2 and 3.2%. The mean abundance of helminths was 0.005-0.155 (av. 0.068), 5-13 times lower than in native congeners. Waterbird counts indicate that the low infection rates cannot be explained by lack of definitive hosts. The results are consistent with the hypothesis that helminths have no regulating effect on the invasive brine shrimp in the Mediterranean. The replacement of the native populations by the invader can be partially explained by a competition mediated by parasites/predators through a differential impact on host fitness. PMID- 25119351 TI - Feline patent Toxoplasma-like coccidiosis among feral cats (Felis catus) in Doha city, Qatar and its immediate surroundings. AB - Doha city has a high feral cat population and studies of hospital records in Doha have shown that human toxoplasmosis also occurs. Clearly, there is a need to understand the role of cats as vectors of human toxoplasmosis in the city and as a first step we assessed the extent of patent Toxoplasma-like coccidial infections among feral cats. Oocysts in cat faeces were detected between June 2008 and April 2010, from a range of locations radiating out of the city centre in concentric semi circular/elliptic rings and by north, west and south divisions within each of the rings. In total 4,652 cats were sampled and overall prevalence of oocysts was 9.1%. Prevalence was 10.1% in the first summer, and then dropped to 8.4% in the following winter and further to 6.8% in the next summer before rising to 10.6% in the final winter of the study; this interaction between annual period and season was significant. There were also significant changes in prevalence across each of the consecutive months of the study, but no clear pattern was evident. Prevalence did not vary significantly by city sector and there was no difference in prevalence between the host sexes. We conclude therefore, that despite minor and significant perturbations, the prevalence of patent Toxoplasma-like coccidial infections among cats in Doha is remarkably stable throughout the year, across years and spatially within the city's districts. PMID- 25119352 TI - Metazoan endoparasites diversity of Pseudoplatystoma corruscans (Siluriformes: Pimelodidae) as an indicator of environmental alterations on a tropical aquatic system. AB - The aim of the present study was to detect the alterations of Pseudoplatystoma corruscans parasite infracommunity structure, after the construction of the Porto Primavera dam on the high Parana River floodplain. The execution of this research was based on 119 host specimens collected between March 2011 and September 2012, and the results were compared to studies performed on periods before the reservoir's construction, when 110 fishes were collected between March 1992 and February 1993. Five parasite species still remain on the environment, despite the environmental modifications: Choanoscolex abscissus, Spasskyelina spinulifera, Nomimoscolex pertierrae, Harriscolex kaparari and Contracaecum sp 2. The Berger Parker dominance index, calculated to the parasite fauna of 1992, did not show the dominance of any species, while, on the present days, this same index accused the dominance of Nomimoscolex pertierrae (49%) and Choanoscolex abscissus (50%). The present study reports the disappearance of Megathylacus travassosi, Contracaecum sp. 1, Contracaecum sp. 3, Procamallanus (Spirocamallanus) sp. and Cucullanus pseudoplatystomae, suggesting the possibility of a local extinction or a host switch of these species. It has also been registered an Acanthocephala specimen, a genus not observed on this host yet. The results here presented show that the antropic influences on natural systems alter the environmental conditions, what is reflected on the richness and diversity parasite levels. PMID- 25119354 TI - Ultrastructural study of Balantidium ctenopharyngodoni Chen, 1955 (Class: Litostomatea) from China with an emphasis on its vestibulum. AB - A detailed description of the fine structure of Balantidium ctenopharyngodoni Chen, 1955 with an emphasis on its vestibulum is given in the present paper. As to the vestibular kinetids, special attention is paid to the characters of T1, T2 microtubules and nematodesmata. Serving as the major skeleton to the vestibular cortex, the T1, T2 and Pc microtubules are described herein and their support function is also discussed. Moreover, the well-developed nematodesmata of the vestibular kinetids that form a large basket-like complex are described in detail. PMID- 25119353 TI - Molecular characterization of two opecoelid trematodes from fishes in the Gulf of Mexico, with a description of a new species of Helicometra. AB - The plagioporine opecoelids Helicometra fasciata (Rudolphi, 1819) Odhner, 1902, and Macvicaria crassigula (Linton, 1910) Bartoli, Bray, and Gibson, 1989 have been reported from fishes in expansive geographic regions, disjointed from their type localities. New material of M. crassigula was collected from near its type locality as well as specimens resembling Helicometra fasciata sensu lato from three triglids in the Gulf of Mexico. Comparisons of the ribosomal DNA (rDNA) sequences, comprising the partial 18S rDNA, internal transcribed spacer region (= ITS1, 5.8S, and ITS2), and partial 28S rDNA gene, from M. crassigula and Helicometra fasciata sensu lato in the Gulf of Mexico were made with sequences deposited in GenBank from those species from the Mediterranean Sea. Results reveal that M. crassigula sensu stricto from the Gulf of Mexico is distinct from the two cryptic species of M. crassigula sensu lato from the Mediterranean Sea and Helicometra fasciata sensu lato in this study differs from H. fasciata sequences from the Mediterranean Sea, thus Helicometra manteri sp. nov. is described. PMID- 25119356 TI - Calamicoptes anatidus sp. nov., a new quill wall mite (Acari: Laminosioptidae) from the Greater Scaup Aythya marila (L.) (Aves: Anseriformes). AB - Calamicoptes anatidus sp. nov., a new species of rarely found parasitic mites of the family Laminosioptidae (Acari: Astigmata) is described from quill walls of wing covert feathers of Aythya marila Linnaeus (Anseriformes: Anatidae) captured in Poland. This is the first record of the family Laminosioptidae on birds of the order Anseriformes and the first record of this mite family in the fauna of Poland. Females of the new species are most similar to those of C. arenariae Lombert, Gaud et Lukoschus, 1984 and differ from them by the presence of the pygidial shield, which covers dorsal and ventro-lateral parts of the opisthosoma, and by having setae c2 and d2 short and subequal in length, and setae se and cp not reaching the metapodonotal shield. PMID- 25119355 TI - Grillotia erinaceus (van Beneden, 1858) (Cestoda:Trypanorhyncha) from whiting in the Black Sea, with observations on seasonality and host-parasite interrelationship. AB - The genus Grillotia Guiart, 1927 is cosmopolitan in its distribution and the type species, G. erinaceus (van Beneden, 1858), has been relatively well studied. However, this study provides infection indices of Grillotia erinaceus from southern and northern Black Sea whiting Merlangius merlangus for the first time. The specimens of Grillotia erinaceus were obtained from subserosa of the anterior oesophagus, stomach, pyloric caeca, liver, ovaries and mesenterium of whiting caught by commercial fishing vessels off Sinop, Turkey and off Balaklava, Ukraine. Fish were examined during the period from May 2011 to April 2012. Prevalence and mean intensity values in 268 fish collected off Sinop in the Black Sea were 18.66% and 1.82 +/- 0.16 parasites per infected fish, respectively. In Ukrainian 166 whiting samples collected off Balaklava in the Black Sea, however, G. erinaceus plerocercus infection prevalence was 10.24% and mean intensity 1.71 +/- 0.75 parasites per infected fish. Infection parameters were also determined at both sampling sites in relation with host length, sex and season. PMID- 25119358 TI - Seven new species of helminths for reptiles from Armenia. AB - Helminthic infections of reptiles habiting in the territory of Armenia are examined. Seven species of helminths new for reptiles from Armenia are registered: Parapharyngodon skrjabini, Oswaldocruzia goezei, Neoxysomatium sp., Telorchis assula, Nematotaenia tarentolae, Mesocestoides lineatus and Spirometra erinacei europea. Descriptions and pictures of them are given. PMID- 25119357 TI - Thermophilic potentially pathogenic amoebae isolated from natural water bodies in Poland and their molecular characterization. AB - The free-living amoebae (FLA) may live in the environment and also within other organisms as parasites and then they are called amphizoic. They are potentially pathogenic for humans and animals and are found in water that is a source of infection. The aim of this study was molecular detection and identification of these FLA in natural water bodies in North-Western Poland to evaluate the risk of the pathogenic amoebae infections. We examined surface water samples collected from 50 sites and first, the tolerance thermic test was performed in order to select thermophilic, potentially pathogenic strains. For molecular identification of FLA, regions of 18S rDNA, 16S rDNA and intergenic spacers were amplified. Acanthamoeba T4 and T16 genotypes of 18S rDNA gene and 18S rDNA of H. vermiformis were detected. We identified two variants of Acanthamoeba T4 genotype, two variants of Acanthamoeba T16 genotype and one variant of H. vermiformis. Identification of the T16 genotype and H. vermiformis in water was for the first time in Poland. Additionally, we made attempts to adapt the RLB method for detection and differentiation of FLA species and strains. PCR seems to be more sensitive than RLB hybridization, though. PMID- 25119359 TI - Molecular detection and characterization of Theileria species in the Philippines. AB - Theileriosis is a tick-borne disease of domestic and wild animals that cause devastating economic loss in livestock in tropical and subtropical regions. Theileriosis is not yet documented in the Philippines as compared to babesiosis and anaplasmosis which are considered major tick-borne diseases that infect livestock in the country and contribute major losses to the livestock industry. The study was aimed to detect Theileria sp. at genus level in blood samples of cattle using polymerase chain reaction (PCR) assay. Specifically, it determined the phylogenetic relationship of Theileria species affecting cattle in the Philippines to other Theileria sp. registered in the GenBank. A total of 292 blood samples of cattle that were collected from various provinces were used. Theileria sp. was detected in 43/292 from the cattle blood samples using PCR assay targeting the major piroplasm surface protein (MPSP) gene. DNA sequence showed high similarity (90-99%) among the reported Theileria sp. isolates in the GenBank and the Philippine isolates of Theileria. Phylogenetic tree construction using nucleotide sequence classified the Philippine isolates of Theileria as benign. However, nucleotide polymorphism was observed in the new isolate based on nucleotide sequence alignment. It revealed that the new isolate can be a new species of Theileria. PMID- 25119360 TI - Repeat region of Brugia malayi sheath protein (Shp-1) carries Dominant B epitopes recognized in filarial endemic population. AB - Transmission of lymphatic filariasis is mediated through microfilariae (L1 stage of the parasite) which is encased in an eggshell called sheath. The sheath protein Shp-1 stabilizes the structure due to the unique repeat region with Met Pro-Pro-Gln-Gly sequences. Microfilarial proteins could be used as transmission blocking vaccines. Since the repeat region of Shp-1 was predicted to carry putative B epitopes, this region was used to analyze its reactivity with clinical samples towards construction of peptide vaccine. In silico analysis of Shp-1 showed the presence of B epitopes in the region 49-107. The polypeptide epitopic region Shp-149-107 was cloned and expressed in Escherichia coli. Antibody reactivity of the Shp-149-107 construct was evaluated in filarial endemic population by ELISA. Putatively immune endemic normals (EN) showed significantly high reactivity (P < 0.05) when compared to all the other categories. Antibody reactivity of Shp-1 repeat region was similar to that of whole protein proving that this region carries B epitopes responsible for its humoral response in humans. Thus this can be employed for inducing anti-microfilarial immunity in the infected population that may lead to reduction in transmission intensity and also it could be used along with other epitopes from different stages of the parasite in order to manage the disease effectively. PMID- 25119361 TI - The helminth fauna study of European common brown frog (Rana temporaria Linnaeus, 1758) in the Volga basin. AB - In this paper we considered information on the helminth fauna of the European common brown frog (Rana temporaria Linnaeus, 1758) from 10 regions of the Volga basin. This study includes consolidated data of different authors over the last 30 years, supplemented by the results of our own research. There are reliably known finds of 29 species of helminths: Monogenea - 1, Trematoda - 21, Nematoda - 7. Trematodes Gorgodera asiatica Pigulevsky, 1945, Paralepoderma cloacicola (Luhe, 1909), mtc. and nematodes Icosiella neglecta (Diesing, 1851) were observed for the first time in a given host on the territory of Russia and the Volga Basin. Six species of worms make the basis of helminth fauna: nematodes Rhabdias bufonis, Oswaldocruzia filiformis, Neoxysomatium brevicaudatum and Cosmocerca ornata, trematode Haplometra cylindracea and monogenea Polystoma integerrimum. These six species are the most common and widespread parasites of the brown frog. For each species of helminths there is the following information included: taxonomic position, localization, area of detection, biology, definitive hosts, geographic distribution, the degree of host-specificity. PMID- 25119362 TI - Comparative analyses of different genetic markers for the detection of Acanthamoeba spp. isolates. AB - Acanthamoeba are widespread free-living amoebae which may cause granulomatous amoebic encephalitis (GAE), keratitis, skin ulcerations and disseminated tissue infection. An important diagnostic and prognostic factor for the treatment of infection is a quick and correct diagnosis of amoebae strains. The aim of our study was to develop a rapid method for detection and identification of pathogenic Acanthamoeba spp. strains from diagnostic material collected from water. In this study we analysed five amplification-based genetic markers (Aca 16S, Ac6/210, GP, JDP, Nelson) used for identification of pathogenic Acanthamoeba spp. strains isolated in water sources in Poland, Iceland and Sweden. Our results demonstrated the presence of pathogenic Acanthamoeba strains in tap water. PCR assay appeared to be a more rapid and sensitive method to detect the presence of amoebae than the limited conventional techniques. Based on our observations, we can confirm that the use of four out of five genetic markers (Aca 16S, Ac 6/210, JDP, GP, Nelson) may be helpful in identification of Acanthamoeba spp. strains, but only one Aca 16S primer pair is a highly specific marker that distinguishes between pathogenic strains of Acanthamoeba and other free-living amoeba families. PMID- 25119363 TI - Foleyellides rhinellae sp. nov. (Nematoda, Onchocercidae) a new filaria parasitizing Rhinella marina (Anura, Bufonidae) in Mexico. AB - A new nematode species, Foleyellides rhinellae sp. nov. (Onchocercidae), is described from specimens found in the body cavity of the cane toad, Rhinella marina (Linnaeus) (Anura, Bufonidae), in the Laguna de Coyuca, Guerrero, in the Pacific slope of Mexico. The new species differs from the other nine species of Foleyellides by infecting bufonid anurans and by the number and arrangement of caudal papillae. Other distinguishing feature of the new species is the size of the left spicule (0.16-0.23 long), the smallest recorded among the species included in the genus. Foleyellides rhinellae sp. nov. is the second known species of the genus recorded from amphibians of Mexico. PMID- 25119364 TI - Monogenean parasites from fishes of the Vaal Dam, Gauteng Province, South Africa II. New locality records. AB - Baseline information on parasitic infections, including monogenean infections on wild fishes, may aid in implementation of proactive measures as opposed to reactive research aimed at crisis control with reference to future aquaculture applications. The aim of this project was to examine the freshwater monogenean fauna of the Vaal Dam, Vaal River system, South Africa. This short communication reports on infection statistics for monogenean species, some representing new locality records. Parasites were collected from host species other than Labeo spp. from the Vaal Dam, during a summer (January 2010) survey. Fish collected using gill nets of varying mesh sizes were weighed and measured. Mucous smears were prepared from the skin and fins with the aid of microscope slides. Fish were killed humanely by severing the spinal cord behind the head. Gills were carefully removed and divided into areas which were separately scraped to investigate potential parasite site preference. The areas examined were dorsal, median and ventral positions on both the anterior and posterior hemibranch. Both mucous smears and gill scrapings were examined with the aid of a stereo microscope. More parasites were collected from the first or second gill arches, the medial position on the gill, and the anterior hemibranch. Preference for either left or right gill set was inconclusive. Spatial distribution of parasites is thought to result from water flow over the gills during respiration. This paper reports a new locality record for the following monogenean species: Quadriacanthus aegypticus, Dactylogyrus extensus, Dactylogyrus minitus, Gyrodactylus kherulensis and Dactylogyrus lamellatus. PMID- 25119365 TI - Ocular system involvement in the course of human trichinellosis. Pathological and diagnostic aspects. AB - Pathomechanism of lesions in the course of trichinellosis was discussed, representing a sum of immunopathologicaI, pathomorphological and biochemical phenomena. Particular attention was devoted to clinical pathology of the visual organ, which prevails at the acute stage of trichinellosis. In evaluation of clinical signs/symptoms manifested in the visual organ traits of its anatomic, morphological structure, function of the eyeball muscles and eyeball vascular system were taken into account. Ocular lesions in the course of trichinellosis reflect in principle angiomyositis due to immunopathology resulting from migration of Trichinella larvae to many organs and to structures of visual system. PMID- 25119366 TI - Differences in snail ecology lead to infection pattern variation of Echinostoma spp. larval stages. AB - The infection patterns of parasites are often tied to host behavior. Although most studies have investigated definitive hosts and their parasites, intermediate host behavior may play a role in shaping the distribution and accumulation of parasites, particularly the larval stages. In an attempt to answer this question, more than 4,500 pulmonate snails were collected from 11 states in the mid Atlantic and Midwestern United States in the summer of 2012. These snails were necropsied and echinostome metecercariae were commonly observed infecting the snails as 2(nd) intermediate hosts (20.0%). The snails included species of 3 genera with distinct differences in the infection patterns of Echinostoma spp. metacercariae among them. Physa spp. (comprising of P. acuta and P. gyrina) snails exhibited a significantly higher prevalence of infection (23.5%) than both Lymnaea columella (11.6%) and Helisoma spp. (comprising of H. anceps and H. trivolvis) (14.2%; P < 0.05), with no difference in prevalence observed between the latter 2 genera (P > 0.05). The intensity of metacercariae within the snail hosts was significantly different between the 3 genera (P < 0.05), with L. columella having the highest intensity (24.3 +/- 5.6), followed by Physa spp. (15.2 +/- 1.5) and Helisoma spp. (5.0 +/- 0.9). Differences in prevalence and intensity were also observed when the different snail families co-habited the same body of water. The disparities in infection patterns are likely due to distinct differences in the behavioral and feeding ecology of the snail hosts. PMID- 25119367 TI - A new brachycladiid species (Digenea) from Gervais' beaked whale Mesoplodon europaeus in north-western Atlantic waters. AB - A new species of the digenean family Brachycladiidae Odhner, 1905 is described from the bile ducts of a Gervais' beaked whale Mesoplodon europaeus Gervais (Ziphiidae) stranded on the North Atlantic coast of Florida. These parasites were assigned to Brachycladium Looss, 1899 and differed from other species of the genus in the relative size of the oral and ventral suckers, the form and size of the eggs and their extremely small body size. A canonical discriminant analysis was used to examine differences between these specimens and the smallest available individuals of B. atlanticum (Abril, Balbuena and Raga, 1991) Gibson, 2005, considered the morphologically closest species. The overall results exhibited significant differences between the two samples and a jack-knife classification showed that 96.2% of the specimens were correctly classified to their group. In view of evidence from morphological data, the specimens from M. europaeus are considered as new to science and are designated as Brachycladium parvulum n. sp. PMID- 25119368 TI - Metazoan parasites from herring (Clupea harengus L.) as biological indicators in the Baltic Sea. AB - Zoographical distribution of metazoan fish parasites in herring, Clupea harengus, from the Baltic Sea was analysed in order to use them as potential biological indicators. A total of 210 herring from six different sampling sites were investigated, harbouring 12 different parasite species [five digeneans (D), one cestode (C), three nematodes (N) and three acanthocephalans (A)]. The distribution of the parasite species differed according to region, with a distinct gradient of decreasing species richness towards the east of the Baltic Sea. The western localities at Kiel Bay, Rugen and Poland had the highest parasite diversity, including the marine parasite species Anisakis simplex (s.s.) (N), Brachyphallus crenatus and Hemiurus luehei (both D). The eastern localities had low parasite species richness, predominated by the freshwater digenean Diplostomum spathaceum. We could identify three different Baltic herring stocks, the spring-spawning herring of the western Baltic reaching from the Kattegat to the German and Polish coast, the stock of the central Baltic proper and the northern stock of C. harengus var. membras of the Gulf of Finland. The limited distribution of the herring parasites within the Baltic Sea enables their use as biological indicators for migration patterns and stock separation. The acanthocephalan Pomphorhynchus laevis that has already been used as an accumulation bioindicator for heavy metals was only recorded for the western herring stocks. However, the presence of mainly generalistic parasites and their uneven distribution patterns make their use as indicators for regional environmental and global change more difficult. PMID- 25119369 TI - Identifying phenotypes involved in susceptibility to Schistosoma mansoni infection in F1B6CBA mice. AB - Schistosomiasis is a disease with a strong genetic component influenced by socioeconomic and ecological factors. Epidemiological studies have identified several genetic regions involved in the schistosomiasis susceptibility. However, it is not well known what physiological traits are predisposing to the disease. The study of experimental infections in inbred mouse strains with variable genetic susceptibility to the disease offers a good opportunity to tackle this question. F1B6CBA hybrid between the most divergent strains was infected in order to characterize the immunophenotypes that correlate with the susceptibility of schistosomiasis disease in mice. Complete blood counts and immunophenotype were determined at 0, 3, 6, and 9 weeks post infection. Nine weeks after cercariae exposure, animals were perfused and worm recovery was assessed. A large number of hepatic lesions, a reduction in the eosinophil and basophil count in the acute phase of infection and the decreased number of monocytes, neutrophils and B lymphocytes are phenotypes associated with increased susceptibility to S. mansoni infection. PMID- 25119370 TI - A new species of Rhinonastes (Monogenoidea, Dactylogyridae), nasal parasite of Prochilodus argenteus (Actinopterygii, Characiformes) from Brazil. AB - A new species of Rhinonastes, hitherto monotypic, is described and illustrated from the nasal cavity of 'curimat', Prochilodus argenteus from Sao Francisco River, Brazil. Rhinonastes curimatae n. sp. presents a male copulatory organ with more than five rings while the type species of the genus is characterized by male copulatory organ with less than two rings. This is the first record of a nasal parasite in P. argenteus. PMID- 25119371 TI - Observations on oocyst development of Eimeria stiedai in rabbits. AB - The formation of the oocyst wall was examined in Eimeria stiedai in the bile duct epithelium of the rabbit and was found to follow the general eimerian pattern. However from the beginning of the formation of the outer layer of the oocyst wall the parasite was surrounded by a rarely reported veil membrane. Cell damage of the bile ducts at the gamogony stage of parasite development is depicted. PMID- 25119372 TI - Increased serum urea to creatinine ratio and its negative correlation with arterial pressure in canine babesiosis. AB - The increase of the serum urea to creatinine ratio (UCR) was observed in dogs infected with Babesia canis. Previous studies have suggested that decrease of blood pressure can be one of the reasons for this phenomenon. In this work statistically significant increase of the UCR was observed in dogs with babesiosis. Comparison of the UCR between 23 azotaemic dogs and 25 non-azotaemic dogs infected with Babesia canis showed statistically significantly higher mean of the UCR in azotaemic dogs. Correlations between UCR and systolic, diastolic and mean arterial pressure (SAP, DAP and MAP) in 48 dogs infected with B. canis were negative (UCR and SAP: r = -0.3909; UCR and DAP: r = -0.3182; UCR and MAP: r = -0.3682) and statistically significant (p < 0.05). This result may indicate contribution of hypotension in the increase of the UCR in canine babesiosis. However, the correlations were not high, and there was no statistically significant correlation between UCR and arterial pressures in azotaemic dogs. Thus, it seems that decrease of blood pressure in dogs with babesiosis explains only partially the cause of increased UCR in infected dogs. The other authors suggested hyperureagenesis and myocardial injury as a potential reason for the increased UCR in canine babesiosis. Thus, further studies are needed to determine causes of increased UCR in dogs with babesiosis, especially on the connection between UCR changes and the concentrations of plasma cardiac troponins and ammonia, and the occurrence of occult blood on fecal examination. PMID- 25119373 TI - Individual growth detection of bacterial species in an in vitro oral polymicrobial biofilm model. AB - Most in vitro studies on the antibacterial effects of antiseptics have used planktonic bacteria in monocultures. However, this study design does not reflect the in vivo situation in oral cavities harboring different bacterial species that live in symbiotic relationships in biofilms. The aim of this study was to establish a simple in vitro polymicrobial model consisting of only three bacterial strains of different phases of oral biofilm formation to simulate in vivo oral conditions. Therefore, we studied the biofilm formation of Actinomyces naeslundii (An), Fusobacterium nucleatum (Fn), and Enterococcus faecalis (Ef) on 96-well tissue culture plates under static anaerobic conditions using artificial saliva according to the method established by Pratten et al. that was supplemented with 1 g l(-1) sucrose. Growth was separately determined for each bacterial strain after incubation periods of up to 72 h by means of quantitative real-time polymerase chain reaction and live/dead staining. Presence of an extracellular polymeric substance (EPS) was visualized by Concanavalin A staining. Increasing incubation times of up to 72 h showed adhesion and propagation of the bacterial strains with artificial saliva formulation. An and Ef had significantly higher growth rates than Fn. Live/dead staining showed a median of 49.9 % (range 46.0-53.0 %) of living bacteria after 72 h of incubation, and 3D fluorescence microscopy showed a three-dimensional structure containing EPS. An in vitro oral polymicrobial biofilm model was established to better simulate oral conditions and had the advantage of providing the well-controlled experimental conditions of in vitro testing. PMID- 25119374 TI - Interactive sections of an Internet-based intervention increase empowerment of chronic back pain patients: randomized controlled trial. AB - BACKGROUND: Chronic back pain (CBP) represents a significant public health problem. As one of the most common causes of disability and sick leave, there is a need to develop cost-effective ways, such as Internet-based interventions, to help empower patients to manage their disease. Research has provided evidence for the effectiveness of Internet-based interventions in many fields, but it has paid little attention to the reasons why they are effective. OBJECTIVE: This study aims to assess the impact of interactive sections of an Internet-based self management intervention on patient empowerment, their management of the disease, and, ultimately, health outcomes. METHODS: A total of 51 patients were recruited through their health care providers and randomly assigned to either an experimental group with full access to the Internet-based intervention or a control group that was denied access to the interactive sections and knew nothing thereof. The intervention took 8 weeks. A baseline, a mid-term after 4 weeks, and a final assessment after 8 weeks measured patient empowerment, physical exercise, medication misuse, and pain burden. RESULTS: All patients completed the study. Overall, the intervention had a moderate effect (F1.52=2.83, P=.03, eta(2)=0.30, d=0.55). Compared to the control group, the availability of interactive sections significantly increased patient empowerment (midterm assessment: mean difference=+1.2, P=.03, d=0.63; final assessment: mean difference=+0.8, P=.09, d=0.44) and reduced medication misuse (midterm assessment: mean difference=-1.5, P=.04, d=0.28; final assessment: mean difference=-1.6, P=.03, d=-0.55) in the intervention group. Both the frequency of physical exercise and pain burden decreased, but to equal measures in both groups. CONCLUSIONS: Results suggest that interactive sections as part of Internet-based interventions can positively alter patients' feelings of empowerment and help prevent medication misuse. Detrimental effects were not observed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02114788; http://www.clinicaltrials.gov/ct2/show/NCT02114788 (Archived by WebCite at http://www.webcitation.org/6ROXYVoPR). PMID- 25119376 TI - Adeno-associated virus-mediated gene transfer targeting normal and traumatized mouse utricle. AB - Balance dysfunction is closely associated with loss of vestibular hair cells (HCs). Gene therapy shows promise when used to protect or regenerate vestibular HCs to preserve or restore adequate vestibular function. Adeno-associated virus (AAV) vectors allow long-term gene expression in the absence of toxicity. To noninvasively define an AAV serotype exhibiting favorable tropism toward the vestibular sensory epithelium, we characterized the transgene expression potential of AAV vectors (serotypes 1, 2, 5, 6 and 8) inoculated into adult mouse utricle via canalostomy. We found that AAV8 was the most effective AAV vector in utricular gene transfer. Swim tests and measurements of auditory brainstem response revealed minimal loss of vestibular function and hearing after canalostomy. In the normal utricle after AAV8 infusion, transduction efficiency peaked at 7 days, and was maintained thereafter, in vestibular HCs, and at 3 days in supporting cells (SCs). In the streptomycin-lesioned utricle, the SC transduction efficiency peaked at 7 days and decreased at 30 days. In conclusion, AAV8-mediated gene transfer via canalostomy facilitates efficient and safe transduction in mouse vestibular sensory epithelium, and may in the future become clinically relevant for human vestibular gene therapy. PMID- 25119375 TI - Adjuvant effects of L. acidophilus LW1 on immune responses to the foot-and-mouth disease virus DNA vaccine in mice. AB - The adjuvant effects of Lactobacillus acidophilus on DNA vaccination are not fully understood. It has been hypothesized that swine-derived Lactobacillus acidophilus SW1 (LASW1) could function as an immune adjuvant to enhance antigen specific immune responses after foot-and-mouth disease (FMD) DNA vaccination in mice. To evaluate the effect of oral LASW1 on the immune response to a DNA vaccine (pRC/CMV-vp1) harboring FMD VP1 gene, anti-FMDV antibody and its isotypes, T-cell proliferation, and cytokine detection were investigated. The results showed that LASW1 was able to enhance FMDV-specific antibody levels and FMDV-neutralizing antibodies. After a booster vaccine, the anti-FMDV antibody titers and FMDV-neutralizing antibodies levels induced by pRC/CMV-vp1 were higher in mice treated with LSAW1 than in the group immunized with pRC/CMV-vp1 alone (the control). Using T-cell proliferation, the stimulation index of the LASW1 group was significantly higher in response to ConA and 146S antigen (P<0.05) than in the control group. Importantly, higher concentrations of IFN-gamma and IFN gamma-producing cells were also observed in splenocytes isolated from the experimental LASW1 mice, indicating that INF-gamma secretion is important to the immune response to LASW1. The results indicate that LASW1 is a promising immune adjuvant in DNA vaccination against FMD when administrated orally. PMID- 25119378 TI - Transduction efficiency of neurons and glial cells by AAV-1, -5, -9, -rh10 and hu11 serotypes in rat spinal cord following contusion injury. AB - Adeno-associated viruses (AAVs) are a promising system for therapeutic gene delivery to neurons in a number of neurodegenerative conditions including spinal cord injuries (SCIs). Considering the role of macrophages and glia in the progression of 'secondary damage', we searched for the optimal vectors for gene transfer to both neurons and glia following contusion SCI in adult rats. Contusion models share many similarities to most human spinal cord traumas. Several AAV serotypes known for their neuronal tropism expressing enhanced green fluorescent protein (GFP) were injected intraspinally following thoracic T10 contusion. We systematically compared the transduction efficacy and cellular tropism of these vectors for neurons, macrophages/microglia, oligodendrocytes, astrocytes and NG2-positive glial cells following contusion SCI. No additional changes in inflammatory responses or behavioral performance were observed for any of the vectors. We identified that AAV-rh10 induced robust transduction of both neuronal and glial cells. Even though efficacy to transduce neurons was comparable to already established AAV-1, AAV-5 and AAV-9, AAV-rh10 transduced significantly higher number of macrophages/microglia and oligodendrocytes in damaged spinal cord compared with other serotypes tested. Thus, AAV-rh10 carries promising potential as a gene therapy vector, particularly if both the neuronal and glial cell populations in damaged spinal cord are targeted. PMID- 25119380 TI - Whole-genome mapping for high-resolution genotyping of Pseudomonas aeruginosa. AB - A variety of molecular typing techniques have been developed to investigate the clonal relationship among bacterial isolates, including those associated with nosocomial infections. In this study, the authors evaluated whole-genome mapping as a tool to investigate the genetic relatedness between Pseudomonas aeruginosa isolates, including metallo beta-lactamase-positive outbreak isolates. PMID- 25119377 TI - SR-A and SREC-I binding peptides increase HDAd-mediated liver transduction. AB - Helper-dependent adenoviral (HDAd) vectors can mediate long-term, high-level transgene expression from transduced hepatocytes without inducing chronic toxicity. However, vector therapeutic index is narrow because of a toxic acute response with potentially lethal consequences elicited by high vector doses. Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs) are major barriers to efficient hepatocyte transduction. We investigated two small peptides (PP1 and PP2) developed by phage display to block scavenger receptor type A (SR A) and scavenger receptor expressed on endothelial cells type I (SREC-I), respectively, for enhancement of HDAd-mediated hepatocyte transduction efficiency. Pre-incubation of J774A.1 macrophages with either PP1 or PP2 prior to HDAd infection significantly reduced viral vector uptake. In vivo, fluorochrome conjugated PP1 and PP2 injected intravenously into mice co-localized with both CD68 and CD31 on KCs and LSECs, respectively. Compared with saline pre-treated animals, intravenous injections of both peptides prior to the injection of an HDAd resulted in up to 3.7- and 2.9-fold increase of hepatic transgene expression with PP1 and PP2, respectively. In addition to greater hepatocyte transduction, compared with control saline injected mice, pre-treatment with either peptide resulted in no increased levels of serum interleukin-6, the major marker of adenoviral vector acute toxicity. In summary, we developed small peptides that significantly increase hepatocyte transduction efficacy and improve HDAd therapeutic index with potential for clinical applications. PMID- 25119381 TI - Soil carbon and nitrogen fractions and crop yields affected by residue placement and crop types. AB - Soil labile C and N fractions can change rapidly in response to management practices compared to non-labile fractions. High variability in soil properties in the field, however, results in nonresponse to management practices on these parameters. We evaluated the effects of residue placement (surface application [or simulated no-tillage] and incorporation into the soil [or simulated conventional tillage]) and crop types (spring wheat [Triticum aestivum L.], pea [Pisum sativum L.], and fallow) on crop yields and soil C and N fractions at the 0-20 cm depth within a crop growing season in the greenhouse and the field. Soil C and N fractions were soil organic C (SOC), total N (STN), particulate organic C and N (POC and PON), microbial biomass C and N (MBC and MBN), potential C and N mineralization (PCM and PNM), NH4-N, and NO3-N concentrations. Yields of both wheat and pea varied with residue placement in the greenhouse as well as in the field. In the greenhouse, SOC, PCM, STN, MBN, and NH4-N concentrations were greater in surface placement than incorporation of residue and greater under wheat than pea or fallow. In the field, MBN and NH4-N concentrations were greater in no-tillage than conventional tillage, but the trend reversed for NO3-N. The PNM was greater under pea or fallow than wheat in the greenhouse and the field. Average SOC, POC, MBC, PON, PNM, MBN, and NO3-N concentrations across treatments were higher, but STN, PCM and NH4-N concentrations were lower in the greenhouse than the field. The coefficient of variation for soil parameters ranged from 2.6 to 15.9% in the greenhouse and 8.0 to 36.7% in the field. Although crop yields varied, most soil C and N fractions were greater in surface placement than incorporation of residue and greater under wheat than pea or fallow in the greenhouse than the field within a crop growing season. Short-term management effect on soil C and N fractions were readily obtained with reduced variability under controlled soil and environmental conditions in the greenhouse compared to the field. Changes occurred more in soil labile than non-labile C and N fractions in the greenhouse than the field. PMID- 25119379 TI - Assessment of oncolytic HSV efficacy following increased entry-receptor expression in malignant peripheral nerve sheath tumor cell lines. AB - Limited expression and distribution of nectin-1, the major herpes simplex virus (HSV) type-1 entry-receptor, within tumors has been proposed as an impediment to oncolytic HSV (oHSV) therapy. To determine whether resistance to oHSVs in malignant peripheral nerve sheath tumors (MPNSTs) was explained by this hypothesis, nectin-1 expression and oHSV viral yields were assessed in a panel of MPNST cell lines using gamma134.5-attenuated (Deltagamma134.5) oHSVs and a gamma134.5 wild-type (wt) virus for comparison. Although there was a correlation between nectin-1 levels and viral yields with the wt virus (R=0.75, P =0.03), there was no correlation for Deltagamma134.5 viruses (G207, R7020 or C101) and a modest trend for the second-generation oHSV C134 (R=0.62, P=0.10). Nectin-1 overexpression in resistant MPNST cell lines did not improve Deltagamma134.5 oHSV output. While multistep replication assays showed that nectin-1 overexpression improved Deltagamma134.5 oHSV cell-to-cell spread, it did not confer a sensitive phenotype to resistant cells. Finally, oHSV yields were not improved with increased nectin-1 in vivo. We conclude that nectin-1 expression is not the primary obstacle of productive infection for Deltagamma134.5 oHSVs in MPNST cell lines. In contrast, viruses that are competent in their ability to counter the antiviral response may derive benefit with higher nectin-1 expression. PMID- 25119383 TI - Factors associated with recently acquired hepatitis C virus infection in people who inject drugs in England, Wales and Northern Ireland: new findings from an unlinked anonymous monitoring survey. AB - Monitoring infections and risk in people who inject drugs (PWID) is important for informing public health responses. In 2011, a novel hepatitis C antibody (anti HCV) avidity-testing algorithm to identify samples compatible with recent primary infection was introduced into a national surveillance survey. PWID are recruited annually, through >60 needle-and-syringe programmes and prescribing services. Of the 980 individuals that could have been at risk of HCV infection, there were 20 (2%) samples that were compatible with recent primary infection. These were more common among: those imprisoned ?5 times [8/213; adjusted odds ratio (aOR) 8.7, 95% confidence interval (CI) 2.04-37.03]; women (8/230; aOR 3.8, 95% CI 1.41 10.38); and those ever-infected with hepatitis B (5/56; aOR 6.25, 95% CI 2.12 18.43). This study is the first to apply this algorithm and to examine the risk factors associated with recently acquired HCV infection in a national sample of PWID in the UK. These findings highlight underlying risks and suggest targeted interventions are needed. PMID- 25119382 TI - Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells. AB - The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo. PMID- 25119385 TI - Adjuvant chemoradiotherapy for squamous cell carcinoma of gallbladder. PMID- 25119386 TI - Mesenteric inflammatory pseudotumor: a case report and comprehensive literature review. AB - PURPOSE: This study aims to provide an overview of the literature on mesenteric/omental inflammatory pseudotumors (IPTs). METHODOLOGY: We present a new case of mesenteric IPT. We also conducted a systematic search of the English language medical literature using PubMed, Medline, Google, and Google Scholar related to mesenteric or omental IPTs. The following search terms were used in various combinations: inflammatory myofibroblastic tumor, IPT, mesentery, and omentum. The search included articles published in the English language between January, 1978 and April, 2014. Studies were excluded if the full text was unavailable or missing information prohibited comparisons. RESULTS: A total of 30 reports concerning 36 patients with inflammatory pseudotumors meeting the aforementioned criteria were included. The patients were aged from 10 months to 68 years (mean, 19.98 +/- 20.5 years); 12 were female (16.75 +/- 16.97 years; range, 10 months to 68 years) and 24 were male (21.6 +/- 21.9 years; range, 18 months to 63 years). Detailed clinical and pathologic characteristics of 36 patients with IPTs are provided in Table 1. CONCLUSION: IPTs may be definitively diagnosed only by histopathological examination and are most effectively treated by resection with negative surgical borders. No consensus has yet been reached regarding when nonsurgical treatment options are most appropriate in management of these lesions. IPTs often recur locally, while distant metastases are very rare. Postoperative close surveillance is essential to detect recurrences early. PMID- 25119388 TI - Social-emotional aspects of male escorting: experiences of men working for an agency. AB - Social situations and emotional correlates associated with male sex work have not been well documented. Most of the research in this area focuses on sexual activity with little mention of other aspects of the job. Yet, research with female sex workers finds significant social and emotional components to sex work. The current study focused on how male sex workers (MSWs) perceived and adapted to the social-emotional aspects of their job. As part of a larger project examining MSWs working for a single escort agency, 40 men (M age, 22.3 years, 75 % Caucasian) located in the mid-Atlantic U.S. participated in semi-structured interviews. The agency owner was also interviewed. Participants reported a range of social and emotional factors regarding sex work and employed a variety of strategies to provide good customer service and adapt to negative experiences. For most, social support was inhibited due to fear of stigmatization that might result if participants disclosed sex work to significant others outside the agency. Instead, interactions within the agency provided core work-related social support for most MSWs. Emotional and relational tasks inherent to escort work grew easier with experience and negativity about the job declined. Our data suggested that socially connected individuals seemed to be more satisfied with sex work. Social and emotional requirements represented a significant but unanticipated component of male sex work to which escorts actively adapted. Escorting may be similar to other service occupations in terms of the social emotional situations and skills involved. PMID- 25119387 TI - Discrimination and depressive symptoms among sexual minority youth: is gay affirming religious affiliation a protective factor? AB - Researchers have examined perceived discrimination as a risk factor for depression among sexual minorities; however, the role of religion as a protective factor is under-investigated, especially among sexual minority youth. Drawing on a cross-sectional study investigating campus climate at a large public university in the U.S. midwest, we examined the role of affiliation with a gay-affirming denomination (i.e., endorsing same-sex marriage) as a moderating factor in the discrimination-depression relationship among self-identified sexual minority (n = 393) and heterosexual youth (n = 1,727). Using multivariate linear regression analysis, religious affiliation was found to moderate the discrimination depression relationship among sexual minorities. Specifically, the results indicated that the harmful effects of discrimination among sexual minority youth affiliated with denominations that endorsed same-sex marriage were significantly less than those among peers who affiliated with denominations opposing same-sex marriage or who identified as secular. In contrast, religious affiliation with gay-affirming denominations did not moderate the discrimination-depression relationship among heterosexual participants. The findings suggest that, although religion and same-sex sexuality are often seen as incompatible topics, it is important when working with sexual minority clients for clinicians to assess religious affiliation, as it could be either a risk or a protective factor, depending on the religious group's stance toward same-sex sexuality. To promote the well-being of sexual minority youth affiliated with denominations opposed to same-sex marriage, the results suggest these faith communities may be encouraged to reconsider their position and/or identify ways to foster youth's resilience to interpersonal discrimination. PMID- 25119389 TI - Capturing sexual violence experiences among battered women using the revised sexual experiences survey and the revised conflict tactics scales. AB - The assessment of intimate partner sexual violence (IPSV) has garnered increased attention in recent years. However, uncertainty about which measure best captures experiences of IPSV remains. The present study focused on the direct comparison of two widely used measures of IPSV: the revised Sexual Experiences Survey (SES) and the revised Conflict Tactics Scales (CTS2). A secondary aim of the study was to extend the scope of IPSV acts by evaluating the presence of pornographic acts and experiences of forced sexual relations with other individuals. The current sample consisted of 138 battered women using the services of shelters. Results indicated that 79.7 % of women reported at least one incident of IPSV on either the CTS2 or the SES. The concordance rate between both measures was 76.8 %, with the highest concordance being for severe sexual violence. The Sexual Violence scale of the CTS2, which is more concise than the SES, identified 16.7 % more cases of IPSV. In addition, 26.1 % of women reported at least one incident involving pornography and 9.4 % had been forced to engage in sexual activities with other individuals. Women who reported experiences associated with pornography were 12-20 times more likely to be victims of severe sexual violence on the two measures. Such findings confirm the high prevalence of sexual violence among this population and indicate how rates can vary depending on the measures used. This study also underscores the relevance of investigating diverse types of violent acts to better understand how IPSV manifests itself. PMID- 25119390 TI - Hepatitis B virus inhibits the expression of CD82 through hypermethylation of its promoter in hepatoma cells. AB - The tumor suppressor gene CD82, also known as KAI1, may act as a general suppressor of metastasis in numerous types of cancer. It is hypothesized that downregulation of CD82 gene expression may be an important factor in the induction of hepatocellular carcinoma (HCC), however the mechanism for this requires further study. In the present study, the relative mRNA and protein expression levels of the CD82 gene were determined in HCC and adjacent non-tumor tissues. The association between the CD82 gene and the hepatitis B virus (HBV) was also investigated, by quantitative polymerase chain reaction, western blotting, luciferase reporter assays and mass spectrometry with matrix-assisted laser desorption/ionization time-of-flight mass array. CD82 expression was shown to be suppressed in response to HCC promoter methylation. Relative CD82 mRNA and protein expression levels were downregulated in HCC tissues (P<0.05). HBx protein inhibited CD82 promoter activity and subsequently the mRNA and protein expression levels. Furthermore, it was demonstrated that HBV could inhibit the expression of CD82 at the transcriptional level, and repress the activity of the CD82 promoter through hypermethylation. In addition, the methyl enzyme inhibitor 5-aza-CdR could induce the CD82 promoter activity and the relative expression level of CD82 mRNA, as observed by an increase in luciferase activity driven by the CD82 promoter. The observations of the present study suggest that hypermethylation of the CD82 promoter may be an event leading to the development of HCC. Low expression of CD82 is likely to be involved in tumor progression. HBV may inhibit the expression of CD82 through hypermethylation of the promoter in hepatoma cells. PMID- 25119394 TI - Oral bacillus Calmette-Guerin vaccine against tuberculosis: why not? AB - The bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for human use against tuberculosis (TB). Although controversy exists about its efficacy, the BCG vaccine is able to protect newborns and children against disseminated forms of TB, but fails to protect adults against active forms of TB. In the last few years, interest in the mucosal delivery route for the vaccine has been increasing owing to its increased capacity to induce protective immune responses both in the mucosal and the systemic immune compartments. Here, we show the importance of this route of vaccination in newly developed vaccines, especially for vaccines against TB. PMID- 25119395 TI - The first report of the vanC1 gene in Enterococcus faecium isolated from a human clinical specimen. AB - The vanC1 gene, which is chromosomally located, confers resistance to vancomycin and serves as a species marker for Enterococcus gallinarum. Enterococcus faecium TJ4031 was isolated from a blood culture and harbours the vanC1gene. Polymerase chain reaction (PCR) assays were performed to detect vanXYc and vanTc genes. Only the vanXYc gene was found in the E. faecium TJ4031 isolate. The minimum inhibitory concentrations of vancomycin and teicoplanin were 2 ug/mL and 1 ug/mL, respectively. Real-time reverse transcription-PCR results revealed that the vanC1and vanXYc genes were not expressed. Pulsed-field gel electrophoresis and southern hybridisation results showed that the vanC1 gene was encoded in the chromosome. E. faecalis isolated from animals has been reported to harbour vanC1gene. However, this study is the first to report the presence of the vanC1gene in E. faecium of human origin. Additionally, our research showed the vanC1gene cannot serve as a species-specific gene of E. gallinarum and that it is able to be transferred between bacteria. Although the resistance marker is not expressed in the strain, our results showed that E. faecium could acquire the vanC1gene from different species. PMID- 25119397 TI - Ectopic tooth superiorly located in the maxillary sinus. PMID- 25119398 TI - Malformation, deformity, and discrepancy: focus on terminology. PMID- 25119396 TI - Odontogenic differentiation of vascular endothelial growth factor-transfected human dental pulp stem cells in vitro. AB - Dental pulp stem cells (DPSCs) can be induced towards odontogenic differentiation. Previous studies have shown that vascular endothelial growth factor (VEGF) is able to induce the osteogenic differentiation of cells, but the effectiveness of VEGF in the odontogenic differentiation of DPSCs remains unclear. This study aimed to investigate the effects of lentivirus-mediated human VEGF gene transfection on the proliferation and odontogenic differentiation of human DPSCs in vitro. DPSCs were transfected with either lentiviral pCDH-CMV-MCS EFI-copGFP (pCDH) vector or recombinant pCDH-VEGF vector, and the growth characteristics of the resulting DPSCs/Vector and DPSCs/VEGF were subsequently assessed. The odontogenic differentiation genes of the two groups of cells, including alkaline phosphatase, osteocalcin, dentin sialophosphoprotein and dentin matrix protein 1 (DMP1), were evaluated by quantitative polymerase chain reaction (qPCR). The specific proteins of odontogenic differentiation, including dentin sialoprotein and DMP1, were analyzed by western blotting. DPSCs/VEGF showed similar proliferation characteristics to DPSCs/Vector during the observation period. qPCR results showed that the relative VEGF gene expression was significantly higher in DPSCs/VEGF than that in DPSCs/Vector two days after transfection (P<0.01). Similarly, western blot analysis showed that the protein expression levels of VEGF were higher in DPSCs/VEGF than those in DPSCs/Vector. On the first, fourth, eighth and 16th days after lentivirus-mediated transfection, the expression of odontogenic differentiation-specific genes and proteins was higher in DPSCs/VEGF than that in DPSCs/Vector. These results indicated that lentivirus-mediated VEGF gene transfection promoted the odontogenic differentiation of human DPSCs in vitro. PMID- 25119399 TI - Pediatric Castleman disease of the parotid. PMID- 25119401 TI - Herpes simpex infection after septorhinoplasty. PMID- 25119400 TI - Foot ischemia after a free fibula flap harvest: immediate salvage with an interpositional sapheneous vein graft. AB - The most dreaded major donor-site complication of free fibula flap is a foot ischemia, which is fortunately rare. Various authors have discussed the efficacy of the use of preoperative imaging methods including color Doppler, magnetic resonance angiography, and conventional angiography. A 25-year-old man presented with a 10-cm mandibular defect after a facial gunshot injury. Lower extremity color Doppler revealed triphasic peroneal, tibialis anterior, and posterior artery flows. A fibula osteocutaneous flap was harvested, and the mandible was reconstructed. However, the suture sites at the donor site began to demonstrate signs of necrosis, abscess formation, and widespread cellulitis beginning from postoperative day 9. Angiogram of the lower extremity on the 13th day demonstrated no flow in the right posterior tibial artery distal to the popliteal artery, whereas the anterior tibial artery had weak flow with collateral filling distally. An emergency bypass with a saphenous vein graft between the popliteal artery and the distal posterior tibial artery was performed. Repeated debridements, local wound care, and vacuum-assisted closure were applied. A skin graft was placed eventually. The extremity healed without severe functional disability. In conclusion, although the arterial anatomy is completely normal in preoperative evaluation, vascular complications may still ocur at the donor fibula free flap site. In addition, emergency cardiovascular bypass surgery, as we experienced, may be necessary for limb perfusion. PMID- 25119402 TI - Papillary cystadenoma of the upper lip. PMID- 25119403 TI - Infantile hemangioma: treatment rate during the proliferating phase. PMID- 25119404 TI - A patient with intraoral fire during tonsillectomy. AB - Perioperative fires inside the mouth can have long-lasting sequelae. They are potentially dangerous both to the patient and to the operation room staff as well. Herein, we present a flash fire in the oropharynx, secondary to electrosurgery during a tonsillectomy operation in a young child. Despite a potentially devastating situation, the patient recovered well within just a week following intraoral burn injuries, and the initially interrupted tonsillectomy operation was completed without complications. The dangerous situations leading to fire hazards and the prevention measures are discussed. PMID- 25119405 TI - Somatotopic organization of trigeminal ganglion: three-dimensional reconstruction of three divisions. AB - Clearing the somatotopic organization of trigeminal ganglion can help us to improve the precision of treatment for trigeminal neuralgia. The distribution of primary afferent perikarya of 3 branches of trigeminal nerve in the trigeminal ganglion was investigated in the rabbit, and 3D model was reconstructed then. After application of wheat germ agglutinin-horseradish peroxidase and DiI to the cut endings of the 3 branches of trigeminal nerve, ophthalmic cells were found in the anteromedial part of the trigeminal ganglion, mandibular cells in the posterolateral part, and maxillary cells in the middle part. The results suggest that the somatotopic organization of the ganglion in rabbits is a mediolateral direction reflecting the mediolateral order of the ophthalmic, maxillary, and mandibular nerves. PMID- 25119407 TI - Intraoperative high-dose epinephrine infiltration in cleft palate repair. PMID- 25119409 TI - Effective treatment of congenital muscular torticollis using botulinum toxin. PMID- 25119410 TI - India: reverse innovation and the dichotomy of medical resources. PMID- 25119411 TI - Treatment of large calvarial defects with bone transport osteogenesis: a preclinical sheep model. AB - BACKGROUND: Bone transport osteogenesis (BTO), distraction of a free portion of bone across a defect, offers an autologous solution to large cranial defects that may allow treatment without permanent hardware implantation. This study establishes a sheep model to evaluate the feasibility and distraction kinetics of BTO. METHODS: Subtotal cranial defects (3.5 * 3.5 cm) were created in 10 young adult sheep and a transport segment (3.5 * 2 cm) traversed the defect at varying distraction rates (0, 0.5, 1.0, and 1.5 mm/day) using semi-buried cranial distractors. After a 6-week consolidation period, sheep were euthanized and the resultant bone was analyzed by CT, histology, and mechanical testing. RESULTS: Gross examination, histology, and 3D CT revealed that control animals had fibrous nonunion whereas distraction animals had ossified defects with fibrous nonunion at the distal docking site. There was one premature consolidation in the 0.5 mm/day group. The volume of bony regenerate in the 0.5, 1.0, and 1.5 mm/day distraction rate groups was statistically indistinct (P = 0.16). The mean flexural moduli (MPa) of non-decalcified samples from the control cranium, transport segment, and bone regenerate were found to be 4.50 +/- 4.9, 6.17 +/- 2.1, and 4.14 +/- 4.8, respectively (P = 0.24). CONCLUSIONS: This experiment provides proof of concept for BTO for large calvarial defects in a sheep model. Distraction at a rate of 0.5 mm per day may place individuals at higher risk for premature consolidation, but distraction rates did not have significant effects on regenerate quantity or quality. Future work will include the use of curvilinear distraction devices for 3-dimensional contour. PMID- 25119412 TI - Osteochondroma of the mandibular condyle: a classification system based on computed tomographic appearances. AB - OBJECTIVE: The objectives of this study were to introduce the classification of osteochondroma of the mandibular condyle based on computed tomographic images and to present our treatment experiences. MATERIALS AND METHODS: From January 2002 and December 2012, a total of 61 patients with condylar osteochondroma were treated in our division. Both clinical and radiologic aspects were reviewed. The average follow-up period was 24.3 months with a range of 6 to 120 months. RESULTS: Two types of condylar osteochondroma were presented: type 1 (protruding expansion) in 50 patients (82.0%) and type 2 (globular expansion) in 11 patients (18.0%). Type 1 condylar osteochondroma presented 5 forms: anterior/anteromedial (58%), posterior/posteromedial (6%), medial (16%), lateral (6%), and gigantic (14%). Local resection was performed on patients with type 1 condylar osteochondroma. Subtotal condylectomy/total condylectomy using costochondral graft reconstruction with/without orthognathic surgeries was performed on patients with type 2 condylar osteochondroma. During the follow-up period, tumor reformation, condyle absorption, and new deformity were not detected. The patients almost reattained facial symmetry. CONCLUSIONS: Preoperative classification based on computed tomographic images will help surgeons to choose the suitable surgical procedure to treat the condylar osteochondroma. PMID- 25119413 TI - Analysis of therapeutic effect of microvascular decompression surgery on idiopathic hemifacial spasm. AB - OBJECTIVE: The objective of this paper is to study the therapeutic effect of microvascular decompression surgery on idiopathic hemifacial spasm with compression on different zones of facial nerve. METHODS: The clinical data of 348 patients with idiopathic hemifacial spasm treated by microvascular decompression surgery were retrospectively analyzed. Patients were divided into 5 groups according to compression on different zones of facial nerve by offending vessels. Root exit point was compressed in 18 patients (group A), transitional zone of brainstem was compressed in 42 patients (group B), attached segment of brainstem was compressed in 35 patients (group C), distal cisternal portion was compressed in 21 patients (group D), and 2 or more zones were compressed in 232 patients (group E). The therapeutic effect was observed, and outcome of excellent and partial good were regarded as effective. RESULTS: Patients were followed up for 0.5 to 2 years. The effective rates were 94.4%, 95.2%, 97.1%, 95.2%, and 93.9% in group A, group B, group C, group D, and group E, respectively.No death occurred during operation,and there were no severe complications such as complete facial paralysis, intracranial hematoma, and hearing loss after operation. CONCLUSION: Microvascular decompression surgery is the first choice for treatment hemifacial spasm. Proper detection of offending vessels and complete decompression may be the key factors to increase the cure rate. PMID- 25119414 TI - Appraisal of efficacy and safety of intralesional injection of high concentration of bleomycin A5 for treatment of huge macrocystic lymphatic malformations in cervical region. AB - The objective of this study was to investigate the therapeutic effects and safety of intralesional injection of high concentration of bleomycin A5 for huge (more than 5 cm in diameter) macrocystic lymphatic malformations (LMs) in the cervical region. Thirty-two patients with huge macrocystic LMs were treated with percutaneous injection of bleomycin A5 in our department between 2006 and 2011. Among them, 13 patients had unilateral submandibular lesions, and 19 patients had lesions in anterior cervical regions. The age of patients ranged from 10 months to 29 years (mean age, 11.4 y). The concentration of the drug was as high as 2.7 mg/mL (8 mg/3 mL) with an addition of dexamethasone. The mean sessions of injection were 1.6 (1-3 sessions). Repeated injection interval was 4 to 6 weeks. The follow-up period was 6 months to 4 years after the last treatment, and the mean follow-up time was 18 months. The results were evaluated based on clinical examination and Doppler ultrasonography scan. The clinical follow-up showed excellent response in 28 of the 32 patients, whereas 4 of the 32 patients also had a satisfactory response. No serious complications were encountered. Intralesional injection of high concentration of bleomycin A5 was an effective and safe treatment of huge macrocystic LMs in the cervical region and can obtain satisfactory results esthetically and functionally without surgery. PMID- 25119415 TI - How many theories on the genetic code do we need? PMID- 25119416 TI - Evidence of three-level trophic transfer of quantum dots in an aquatic food chain by using bioimaging. AB - In this study, we demonstrated the three-level trophic transfer of quantum dots (QDs) within the aquatic food chain. Using bioimaging, we observed QD transfer from protozoa (Astasia longa) to zooplankton (Moina macrocopa) to fish (Danio rerio). Bioimaging is an effective tool that can improve our understanding of the delivery of nanomaterials in vivo. Measurement with an intravital multiphoton laser scanning microscope visually proved the transfer of QDs from the first to the second and the second to the third levels. As QDs may be passed from lower organisms to humans via the food chain, our findings have implications for the safety of their use. PMID- 25119418 TI - Utility of models of the gastrointestinal tract for assessment of the digestion and absorption of engineered nanomaterials released from food matrices. AB - Engineered metal/mineral, lipid and biochemical macromolecule nanomaterials (NMs) have potential applications in food. Methodologies for the assessment of NM digestion and bioavailability in the gastrointestinal tract are nascent and require refinement. A working group was tasked by the International Life Sciences Institute NanoRelease Food Additive project to review existing models of the gastrointestinal tract in health and disease, and the utility of these models for the assessment of the uptake of NMs intended for food. Gastrointestinal digestion and absorption could be addressed in a tiered approach using in silico computational models, in vitro non-cellular fluid systems and in vitro cell culture models, after which the necessity of ex vivo organ culture and in vivo animal studies can be considered. Examples of NM quantification in gastrointestinal tract fluids and tissues are emerging; however, few standardized analytical techniques are available. Coupling of these techniques to gastrointestinal models, along with further standardization, will further strengthen methodologies for risk assessment. PMID- 25119417 TI - Toxic responses in rat embryonic cells to silver nanoparticles and released silver ions as analyzed via gene expression profiles and transmission electron microscopy. AB - After exposing rat embryonic cells to 20 MUg/mL of silver nanoparticle (NP) suspension and their released ions for different time periods, silver nanoparticles were found in cellular nuclei, mitochondria, cytoplasm and lysosomes by transmission electron microscopy (TEM). We also observed mitochondrial destruction, distension of endoplasmic reticulum and apoptotic bodies. Global gene expression analysis showed a total of 279 genes that were up regulated and 389 genes that were down-regulated in the silver-NP suspension exposure group, while 3 genes were up-regulated and 41 genes were down-regulated in the silver ion exposure group. Further, the GO pathway analysis suggested that these differentially expressed genes are involved in several biological processes, such as energy metabolism, oxygen transport, enzyme activities, molecular binding, etc. It is possible that inhibition of oxygen transport is mediated by the significant down-regulation of genes of the globin family, which might play an important role in silver ion-induced toxicity. KEGG pathway analysis showed that there were 23 signal pathways that were affected in the cells after exposure to silver-NP suspension, but not silver ion alone. The most significant change concerned inflammatory signal pathways, which were only found in silver-NP suspension exposed cells, indicating that inflammatory response might play an important role in the mechanism(s) of silver-NP-induced toxicity. The significant up-regulation of matrix metalloproteinases 3 and 9 suggests that silver NPs could induce extracellular matrix degradation via an inflammatory signaling pathway. The significant up-regulation of secretory leukocyte peptidase inhibitor and serine protease inhibitor 2c was considered to be an embryonic cellular defense mechanism in response to silver-NP-induced inflammation. PMID- 25119419 TI - Optimising the use of commercial LAL assays for the analysis of endotoxin contamination in metal colloids and metal oxide nanoparticles. AB - Engineered nanoparticles (NP) are generally contaminated by bacterial endotoxin, a ubiquitous bacterial molecule with significant toxic and inflammatory effects. The presence of endotoxin, if not recognised, can be responsible for many of the in vitro and in vivo effects attributed to NPs. The Limulus Amoebocyte Lysate (LAL) assay, the test requested by regulatory authorities for assessing endotoxin contamination in products for human use, is not immediately applicable for testing endotoxin in NP preparations, mainly due to the possible interference of NPs with the assay readouts and components. In this study, we have compared different commercially available LAL assays for detecting endotoxin in gold, silver and iron oxide NPs. Different NP chemistry, concentrations and surface coatings could differently interfere with the LAL assays' results. After accurate testing of the possible interaction/interference of NPs with the various assay components, the modified chromogenic LAL assay proved the most suitable assay for measuring endotoxin in NP samples, provided the appropriate controls are performed. Thus, endotoxin determination can be performed in NP preparation with commercial LAL assays only after assay validation, i.e. once possible interference of NPs with the assay components and readouts has been excluded. PMID- 25119420 TI - Problem gambling subtypes based on psychological distress, alcohol abuse and impulsivity. AB - The notion of comorbidities within problem gambling populations has important clinical implications, particularly for appropriate treatment matching. The comorbidities most commonly cited in problem gambling literature include depression, anxiety, alcohol abuse and impulsivity. Previous research shows evidence of patterns in multiple co-occurring comorbidities and that there may be different subtypes of gamblers based on these patterns. To further the current understanding of gambling subtypes, the aim of our study was to identify subtypes of gamblers currently in treatment. Hierarchical Cluster Analysis yielded four mutually exclusive groups of 202 gamblers: (1) gamblers with comorbid psychological problems (35%); (2) 'pure' gamblers without other comorbidities (27%); (3) gamblers with comorbid alcohol abuse (25%); and (4) 'multimorbid' gamblers (13%). The four groups differed on demographic information, drug use and gambling behaviours including gambling activity and problem gambling severity. Gamblers with comorbid psychological problems were more likely to be older women on low income, more likely to report a family history of psychological problems and were more often electronic gaming machine players. As expected, 'pure' gamblers had lower problem gambling severity and were more likely to report current abstinence. Gamblers with comorbid alcohol abuse were more likely to be young men who used stimulant drugs, endorsed a higher quality of life and worked full-time. 'Multimorbid' gamblers were elevated on all comorbidities, had general problems related to their health and wellbeing and reported high rates of hostility and aggression. These groups combine elements of existing conceptual models of gambling subtypes and may require different treatments. PMID- 25119422 TI - Targeting IgE to facilitate oral immunotherapy for food allergy: a potential new role for anti-IgE therapy? AB - Food allergy is a major public health problem without satisfactory treatment options. Of several new treatments being studied, oral immunotherapy (OIT) appears to be the most promising. Unfortunately, OIT is associated with an unacceptably high frequency of allergic reactions. However, recent studies suggest that OIT might be made safer and faster when performed in conjunction with anti-IgE monoclonal antibody as an adjunctive treatment. PMID- 25119421 TI - Cannabis-related impairment: the impacts of social anxiety and misconceptions of friends' cannabis-related problems. AB - OBJECTIVE: Socially anxious cannabis users are especially vulnerable to cannabis related impairment, yet mechanisms underlying this vulnerability remain unclear. Socially anxious persons may use cannabis despite related problems if they believe such problems are common, and thus socially acceptable. Yet no known studies have examined the impact of beliefs regarding others' cannabis-related problems on one's own use-related problems. METHOD: This study investigated the impact of beliefs about a close friend's experience with cannabis-related problems on the relationship between social anxiety and cannabis-related problems. The sample consisted of 158 (75% female) current (past-month) cannabis using undergraduates. RESULTS: Believing one's friend experienced more cannabis problems was related to experiencing more cannabis-related problems oneself. In fact, perceived friend's problems accounted for 40% of the unique variance in one's own cannabis problems. Descriptive norms (others' use) and injunctive norms (others' approval of risky use) were unrelated to the number of one's own problems. Social anxiety was related to experiencing more cannabis problems. This relation was moderated by perceived friend's problems such that greater social anxiety was related to more cannabis-related problems among participants who believed their friend experienced more cannabis-related problems. This was not the case among participants who believed their friend experienced fewer problems. CONCLUSIONS: Normative beliefs regarding a close friend's cannabis problems were robustly and uniquely related to experiencing more cannabis-related impairment. Beliefs regarding friends' experience with cannabis-related problems may play an especially important role in the experience of cannabis-related problems among socially anxious users. PMID- 25119423 TI - Steroid withdrawal in kidney allograft recipients. AB - This review highlights the aggregate of knowledge obtained from the temporal trend of kidney transplant immune suppression. We will discuss the burden of steroid side effects and their impact on quality of life in kidney allograft recipients, which have led to minimizing steroid exposure. Issues arising since the inception of the concept of steroid withdrawal will be discussed, along with how they have continually led to a shift in research focus on this subject matter. The usefulness of surveillance biopsies and how further elucidation of the pathophysiology of interstitial fibrosis and tubular atrophy could contribute to improving long-term allograft outcomes will also be discussed. We will elaborate on the role of calcineurin inhibitor minimization alongside steroid withdrawal in improving long-term graft survival. Future expectations of subsequent studies with a view to improving overall kidney allograft outcomes by eliminating attendant problems associated with steroids will also be covered. PMID- 25119426 TI - Structure, stability and photocatalytic H2 production by Cr-, Mn-, Fe-, Co-, and Ni-substituted decaniobate clusters. AB - Here we report synthesis and characterization of early transition-metal(TM) substituted decaniobates as a continuation of our previous report of tetramethylammonium (TMA) salt of FeNb9 and NiNb9: TMA6[H2Cr(III)Nb9O28].14H2O (1, CrNb9), TMA8[Mn(III)Nb9O28].29H2O (2, MnNb9) and TMA7[H2Co(II)Nb9O28].25H2O (3, CoNb9). Among the TM-substituted decaniobates, CoNb9 or NiNb9 exhibit a higher photocatalytic H2 evolution activity in methanol-water mixtures than others. PMID- 25119425 TI - The effect of the cation alkyl chain branching on mutual solubilities with water and toxicities. AB - The design of ionic liquids has been focused on the cation-anion combinations but other more subtle approaches can be used. In this work the effect of the branching of the cation alkyl chain on the design of ionic liquids (ILs) is evaluated. The mutual solubilities with water and toxicities of a series of bis(trifluoromethylsulfonyl)-based ILs, combined with imidazolium, pyridinium, pyrrolidinium, and piperidinium cations with linear or branched alkyl chains, are reported. The mutual solubility measurements were carried out in the temperature range from (288.15 to 323.15) K. From the obtained experimental data, the thermodynamic properties of the solution (in the water-rich phase) were determined and discussed. The COnductor like Screening MOdel for Real Solvents (COSMO-RS) was used to predict the liquid-liquid equilibrium. Furthermore, molecular dynamic simulations were also carried out aiming to get a deeper understanding of these fluids at the molecular level. The results show that the increase in the number of atoms at the cation ring (from five to six) leads to a decrease in the mutual solubilities with water while increasing their toxicity, and as expected from the well-established relationship between toxicities and hydrophobicities of ILs. The branching of the alkyl chain was observed to decrease the water solubility in ILs, while increasing the ILs solubility in water. The inability of COSMO-RS to correctly predict the effect of branching alkyl chains toward water solubility on them was confirmed using molecular dynamic simulations to be due to the formation of nano-segregated structures of the ILs that are not taken into account by the COSMO-RS model. In addition, the impact of branched alkyl chains on the toxicity is shown to be not trivial and to depend on the aromatic nature of the ILs. PMID- 25119424 TI - Nitroso Diels-Alder (NDA) reaction as an efficient tool for the functionalization of diene-containing natural products. AB - This review describes the use of nitroso Diels-Alder reactions for the functionalization of complex diene-containing natural products in order to generate libraries of compounds with potential biological activity. The application of this methodology to the structural modification of a series of natural products (thebaine, steroidal dienes, rapamycin, leucomycin, colchicine, isocolchicine and piperine) is discussed using relevant examples from the literature from 1973 onwards. The biological activity of the resulting compounds is also discussed. Additional comments are provided that evaluate the methodology as a useful tool in organic, bioorganic and medicinal chemistry. PMID- 25119428 TI - The relationship between electronic nursing care reminders and missed nursing care. AB - The purpose of the study was to explore relationships between nurses' perceptions of the impact of health information technology on their clinical practice in the acute care setting, their use of electronic nursing care reminders, and episodes of missed nursing care. The study aims were accomplished with a descriptive design using adjusted correlations. A convenience sample (N = 165) of medical and/or surgical, intensive care, and intermediate care RNs working on acute care hospital units participated in the study. Nurses from 19 eligible nursing units were invited to participate. Adjusted relationships using hierarchical multiple regression analyses indicated significant negative relationships between missed nursing care and nursing care reminders and perceptions of health information technology. The adjusted correlations support the hypotheses that there is a relationship between nursing care reminder usage and missed nursing care and a relationship between health information technology and missed nursing care. The relationships are negative, indicating that nurses who rate higher levels of reminder usage and health information technology have decreased reports of missed nursing care. The study found a significant relationship between nursing care reminders usage and decreased amounts of missed nursing care. The findings can be used in a variety of improvement endeavors, such as encouraging nurses to utilize nursing care reminders, aid information system designers when designing nursing care reminders, and assist healthcare organizations in assessing the impact of technology on nursing practice. PMID- 25119427 TI - GATA6 loss-of-function mutations contribute to familial dilated cardiomyopathy. AB - Dilated cardiomyopathy (DCM), the most prevalent form of primary heart muscle disease, is the third most common cause of heart failure and the most frequent reason for cardiac transplantation. Mounting evidence has demonstrated that genetic risk factors are crucial in the pathogenesis of DCM. However, DCM is genetically heterogeneous, and the genetic basis of DCM in a large majority of cases remains unclear. In the current study, the coding exons and flanking introns of the GATA6 gene, which encodes a zinc-finger transcription factor essential for cardiogenesis, was sequenced in 140 unrelated patients with DCM, and two novel heterozygous mutations, p.C447Y and p.H475R, were identified in two index patients with DCM, respectively. Analysis of the pedigrees showed that in each family the mutation co-segregated with DCM transmitted in an autosomal dominant pattern, with complete penetrance. The missense mutations were absent in 400 control chromosomes and predicted to be disease-causing by MutationTaster or probably damaging by PolyPhen-2. The alignment of multiple GATA6 proteins across species revealed that the altered amino acids were completely conserved evolutionarily. The functional assays showed that the mutated GATA6 proteins were associated with significantly reduced transcriptional activation in comparison with their wild-type counterpart. To the best of our knowledge, this is the first study on the association of GATA6 loss-of-function mutations with enhanced susceptibility to familial DCM, which provides novel insight into the molecular mechanism of DCM and suggests potential implications for the antenatal prophylaxis and allele-specific treatment of DCM. PMID- 25119430 TI - Dual changes in conformation and optical properties of fluorophores within a metal-organic framework during framework construction and associated sensing event. AB - Microsized chemosensor particle (CPP-16, CPP means coordination polymer particle), which is made from a metal-organic framework (MOF), is synthesized using pyrene-functionalized organic building block. This building block contains three important parts, a framework construction part, a Cu(2+) detection part, and a fluorophore part. PXRD studies have revealed that CPP-16 has a 3D cubic structure of MOF-5. During both MOF formation and sensing event, fluorophores within CPP-16 undergo dual changes in conformation and optical properties. After MOF construction, pyrene moieties experience an unusual complete conversion from monomer to excimer form. This conversion takes place due to a confinement effect induced by space limitations within the MOF structure. The selective sensing ability of CPP-16 on Cu(2+) over many other metal ions is verified by emission spectra and is also visually identified by fluorescence microscopy images. Specific interaction of Cu(2+) with binding sites within CPP-16 causes a second conformational change of the fluorophores, where they change from stacked excimer (CPP-16) to quenched excimer states (CPP-16.Cu(2+)). PMID- 25119431 TI - A general diastereoselective catalytic vinylogous aldol reaction among tetramic acid-derived pyrroles. AB - A catalytic diastereoselective aldol reaction has been developed for N1 arylated/C2-O-silylated/C3-methylated and brominated/C4-O-methylated pyrroles in its reactions with various aldehydes. Syn adducts emerge with regard to the vicinal nitrogen and oxygen heteroatom substituents. The N1-aryl residue undergoes oxidative cleavage, and the C3-bromine atom undergoes palladium mediated coupling reactions, both without disturbing the newly created stereocenters. PMID- 25119429 TI - CCR5 controls immune and metabolic functions during Toxoplasma gondii infection. AB - CCR5, an important receptor related to cell recruitment and inflammation, is expressed during experimental Toxoplasma gondii infection. However, its role in the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we inoculated WT and CCR5(-/-) mice with a sub lethal dose of the parasite by oral route. CCR5(-/-) mice were extremely susceptible to infection, presenting higher parasite load and lower tissue expression of IL-12p40, IFN-gamma, TNF, IL-6, iNOS, Foxp3, T-bet, GATA-3 and PPARalpha. Although both groups presented inflammation in the liver with prominent neutrophil infiltration, CCR5(-/-) mice had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated serum triglycerides and transaminases. PPARalpha agonist Gemfibrozil improved the vacuolization but did not rescue CCR5(-/-) infected mice from high serum triglycerides levels and enhanced mortality. We also found intense inflammation in the ileum of CCR5(-/-) infected mice, with epithelial ulceration, augmented CD4 and decreased frequency of NK cells in the gut lamina propria. Most interestingly, these findings were accompanied by an outstanding accumulation of neutrophils in the ileum, which seemed to be involved in the gut immunopathology, once the depletion of these cells was accompanied by reduced local damage. Altogether, these data demonstrated that CCR5 is essential to the control of T. gondii infection and to maintain the metabolic, hepatic and intestinal integrity. These findings add novel information on the disease pathogenesis and may be relevant for directing future approaches to the treatment of multi-deregulated diseases. PMID- 25119432 TI - Radical scavenging ability of gallic acid toward OH and OOH radicals. Reaction mechanism and rate constants from the density functional theory. AB - Gallic acid is a ubiquitous compound, widely distributed in the vegetal kingdom and frequently found in the human diet. In the present work, its primary antioxidant activity has been investigated using the density functional theory (DFT), and the quantum mechanics-based test for overall free radical scavenging activity (QM-ORSA) protocol. It was found that gallic acid is a better antioxidant than the reference compound, Trolox, regardless of the polarity of the environment. In addition, gallic acid is predicted to be among the best peroxyl radical scavengers identified so far in nonpolar (lipid) media. This compound is capable of scavenging hydroxyl radicals at diffusion-limited rates, and hydroperoxyl radicals with rate constants in the order of 10(5) M(-1) s(-1). The deprotonation of gallic acid, in aqueous solution, is predicted to increase the protective action of this compound against oxidative stress. Gallic acid was also identified as a versatile scavenger, capable of rapidly deactivating a wide variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) via electron transfer at physiological pH. PMID- 25119435 TI - Abstracts from the ESP Meeting 2014. PMID- 25119433 TI - Risk factors for linezolid-associated thrombocytopenia in adult patients. AB - OBJECTIVES: Thrombocytopenia (TP) is a common adverse effect of linezolid (LZD). However, risk factors for LZD-associated TP have been reported in Western patients with relatively heavy body weight. The aim of this study was to determine the risk factors for LZD-associated TP in Asian population. MATERIALS AND METHODS: A retrospective cohort study was conducted among 101 consecutive patients who received LZD therapy (1,200 mg/day) between July 2003 and December 2013 at a tertiary referral hospital in Tokyo, Japan. The patients with obvious other causes for TP were excluded. The information of target infectious disease, patients' age, gender, body weight, body mass index, baseline serum creatinine (SCr), baseline platelet count, and treatment duration was collected retrospectively. TP was defined as >= 50% decrease in platelet count from baseline. Bi- and multi-variate analyses were performed. RESULTS: A total of 101 patients were included (mean age [SD] 64 [18]; male gender [%], 57 [56]). Median duration [range] of LZD therapy was 14 days [1-67]. LZD-associated TP was identified in 42 patients (42%). For TP, adjusted odds ratio (OR) [95% CI] of daily per kg dose (DPKD) and SCr was 1.14 [1.05-1.26] and 1.51 [1.01-2.50], respectively. CONCLUSIONS: Higher DPKD and elevated SCr are significantly associated with LZD-associated TP. These findings suggest that daily dose of LZD should be adjusted using body weight, as typically done in pediatrics, in adults as well. Renal function also should be considered for dose adjustment. PMID- 25119436 TI - Synthesis, structure, and magnetic and electrochemical properties of quasi-linear and linear iron(I), cobalt(I), and nickel(I) amido complexes. AB - Three potassium crown ether salts, [K(Et2O)2(18-crown-6)][Fe{N(SiMe3)Dipp}2] (1a; Dipp = C6H3-2,6-Pr(i)2), [K(18-crown-6)][Fe{N(SiMe3)Dipp}2].0.5PhMe (1b), and [K(18-crown-6)][M{N(SiMe3)Dipp}2] (M = Co, 2; M = Ni, 3), of the two-coordinate linear or near-linear bis-amido monoanions [M{N(SiMe3)Dipp}2](-) (M = Fe, Co, Ni) were synthesized by one-electron reduction of the neutral precursors M{N(SiMe3)Dipp}2 with KC8 in the presence of 18-crown-6. They were characterized by X-ray crystallography, UV-vis spectroscopy, cyclic voltammetry, and magnetic measurements. The anions feature lengthened M-N bonds in comparison with their neutral precursors, with slightly bent coordination (N-Fe-N = ca. 172 degrees ) for the iron(I) complex, but linear coordination for the cobalt(I) and nickel(I) complexes. Fits of the temperature dependence of chiMT of 1 and 2 reveal that the iron(I) and cobalt(I) complexes have large negative D zero-field splittings and a substantial orbital contribution to their magnetic moments with L = 2, whereas the nickel(I) complex has at most a small orbital contribution to its magnetic moment. The magnetic results have been used to propose an ordering of the 3d orbitals in each of the complexes. PMID- 25119434 TI - Structural study of the RIPoptosome core reveals a helical assembly for kinase recruitment. AB - Receptor interaction protein kinase 1 (RIP1) is a molecular cell-fate switch. RIP1, together with Fas-associated protein with death domain (FADD) and caspase 8, forms the RIPoptosome that activates apoptosis. RIP1 also associates with RIP3 to form the necrosome that triggers necroptosis. The RIPoptosome assembles through interactions between the death domains (DDs) of RIP1 and FADD and between death effector domains (DEDs) of FADD and caspase-8. In this study, we analyzed the overall structure of the RIP1 DD/FADD DD complex, the core of the RIPoptosome, by negative-stain electron microscopy and modeling. The results show that RIP1 DD and FADD DD form a stable complex in vitro similar to the previously described Fas DD/FADD DD complex, suggesting that the RIPoptosome and the Fas death-inducing signaling complex share a common assembly mechanism. Both complexes adopt a helical conformation that requires type I, II, and III interactions between the death domains. PMID- 25119439 TI - Echinocandin-induced eosinophilia: a case report. AB - Drug-induced eosinophilia is difficult to diagnose. Severe organ damage can occur if it is left untreated. Presently, caspofungin is the only echinocandin that has been reported to cause eosinophilia. A patient who developed eosinophilia after exposure to caspofungin and re-challenge with anidulafungin is presented. Eosinophilia resolved upon discontinuation of both drugs. PMID- 25119438 TI - Bmovo-1 regulates ovary size in the silkworm, Bombyx mori. AB - The regulation of antagonistic OVO isoforms is critical for germline formation and differentiation in Drosophila. However, little is known about genes related to ovary development. In this study, we cloned the Bombyx mori ovo gene and investigated its four alternatively spliced isoforms. BmOVO-1, BmOVO-2 and BmOVO 3 all had four C2H2 type zinc fingers, but differed at the N-terminal ends, while BmOVO-4 had a single zinc finger. Bmovo-1, Bmovo-2 and Bmovo-4 showed the highest levels of mRNA in ovaries, while Bmovo-3 was primarily expressed in testes. The mRNA expression pattern suggested that Bmovo expression was related to ovary development. RNAi and transgenic techniques were used to analyze the biological function of Bmovo. The results showed that when the Bmovo gene was downregulated, oviposition number decreased. Upregulation of Bmovo-1 in the gonads of transgenic silkworms increased oviposition number and elevated the trehalose contents of hemolymph and ovaries. We concluded that Bmovo-1 was involved in protein synthesis, contributing to the development of ovaries and oviposition number in silkworms. PMID- 25119440 TI - Spleen enlargement is a common finding in acute Puumala hantavirus infection and it does not associate with thrombocytopenia. AB - The pathogenesis of thrombocytopenia in Puumala hantavirus (PUUV) infection is probably multifactorial. We aimed to evaluate the possible spleen enlargement during acute PUUV infection, and to determine its association with thrombocytopenia and disease severity. Magnetic resonance imaging (MRI) of the spleen was performed in 20 patients with acute PUUV infection. MRI was repeated 5 8 months later. The change in spleen length was compared with markers describing the severity of the disease. In all patients, the spleen length was increased in the acute phase compared with the control phase (median 129 mm vs 111 mm, p < 0.001). The change correlated with maximum C-reactive protein value (r = 0.513, p = 0.021) and inversely with maximum leukocyte count (r = -0.471, p = 0.036), but not with maximum serum creatinine level or minimum platelet count. Enlarged spleen, evaluated by MRI, was shown to be a common finding during acute PUUV infection. However, it does not associate with thrombocytopenia and acute kidney injury. PMID- 25119441 TI - Murine typhus in elderly patients: a prospective study of 49 patients. AB - BACKGROUND: The characteristics of Rickettsia typhi infection in elderly patients have not been extensively described in the literature. METHODS: We conducted a prospective study on murine typhus in patients > 65 years old in two endemic areas of Greece. RESULTS: Forty-nine elderly patients were analyzed, including 30 (61.2%) males. The clinical triad of fever (100% of patients), headache (83.7%), and rash (73.5%), occurred in 63% of patients, whereas malaise (85.7%), anorexia (65.3%), and myalgia (59.2%) were also common. Frequent laboratory findings were transaminasemia (89.8%), lactate dehydrogenase elevation (65.3%), hematuria (55.1%), thrombocytopenia (53.1%), anemia (51%), leucopenia (40.8%), and mild hyponatremia (23.5%). Complications developed in 16 patients (32.7%); no deaths were recorded. CONCLUSIONS: The main clinical and laboratory characteristics of murine typhus are similar in elderly and younger adults. However, elderly patients have a more severe clinical picture, evidenced by a higher complication rate and longer duration of fever, even with appropriate treatment. To our knowledge, this is the first study to focus on murine typhus in a geriatric population. PMID- 25119442 TI - NUNDO: a numerical model of a human torso phantom and its application to effective dose equivalent calculations for astronauts at the ISS. AB - The health effects of cosmic radiation on astronauts need to be precisely quantified and controlled. This task is important not only in perspective of the increasing human presence at the International Space Station (ISS), but also for the preparation of safe human missions beyond low earth orbit. From a radiation protection point of view, the baseline quantity for radiation risk assessment in space is the effective dose equivalent. The present work reports the first successful attempt of the experimental determination of the effective dose equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular activity (IVA). This was achieved using the anthropomorphic torso phantom RANDO((r)) equipped with more than 6,000 passive thermoluminescent detectors and plastic nuclear track detectors, which have been exposed to cosmic radiation inside the European Space Agency MATROSHKA facility both outside and inside the ISS. In order to calculate the effective dose equivalent, a numerical model of the RANDO((r)) phantom, based on computer tomography scans of the actual phantom, was developed. It was found that the effective dose equivalent rate during an EVA approaches 700 MUSv/d, while during an IVA about 20 % lower values were observed. It is shown that the individual dose based on a personal dosimeter reading for an astronaut during IVA results in an overestimate of the effective dose equivalent of about 15 %, whereas under an EVA conditions the overestimate is more than 200 %. A personal dosemeter can therefore deliver quite good exposure records during IVA, but may overestimate the effective dose equivalent received during an EVA considerably. PMID- 25119444 TI - Growing dynamical facilitation on approaching the random pinning colloidal glass transition. AB - Despite decades of research, it remains to be established whether the transformation of a liquid into a glass is fundamentally thermodynamic or dynamic in origin. Although observations of growing length scales are consistent with thermodynamic perspectives, the purely dynamic approach of the Dynamical Facilitation (DF) theory lacks experimental support. Further, for vitrification induced by randomly freezing a subset of particles in the liquid phase, simulations support the existence of an underlying thermodynamic phase transition, whereas the DF theory remains unexplored. Here, using video microscopy and holographic optical tweezers, we show that DF in a colloidal glass forming liquid grows with density as well as the fraction of pinned particles. In addition, we observe that heterogeneous dynamics in the form of string-like cooperative motion emerges naturally within the framework of facilitation. Our findings suggest that a deeper understanding of the glass transition necessitates an amalgamation of existing theoretical approaches. PMID- 25119443 TI - The design and discovery of lixisenatide for the treatment of type 2 diabetes mellitus. AB - INTRODUCTION: Lixisenatide is a once-daily short-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) used in the treatment of type 2 diabetes mellitus (T2DM). It is used in combination with oral antidiabetics and/or basal insulin in patients inadequately controlled on these medications and who are undergoing diet and lifestyle modification. GLP-1RAs glucose-dependently increase insulin secretion, decrease glucagon secretion, and slow gastric emptying, thereby improving glycemic control. GLP-1RAs are associated with body weight benefits and low rates of hypoglycemia which are welcome in patients with T2DM. AREAS COVERED: The authors describe the identification of GLP-1RAs as suitable targets for modification with structure-inducing probe technology to improve stability and resistance to proteolytic degradation. Clinical studies have assessed lixisenatide across > 5000 patients as a monotherapy or add-on to a variety of commonly used antidiabetic medications. These studies highlighted the effects of lixisenatide on gastric emptying, explaining its particular improvements in postprandial plasma glucose (PPG) excursions and underscoring its efficacy in combination with insulin glargine. Lixisenatide was well tolerated, with nausea and vomiting being the most frequently reported adverse events. EXPERT OPINION: The once-daily administration of lixisenatide as well as its substantial sustained effect on gastric emptying and, hence, PPG excursions are all important features compared with the other GLP-1RAs. The combination of two injectables, such as basal insulin to lower fasting plasma glucose and a GLP-1RA that curtails PPG excursions, is clinically valuable and could differentiate lixisenatide from other GLP-1RAs, especially from those continuously acting GLP 1RAs with little effect on gastric emptying and PPG excursions. PMID- 25119446 TI - Breaking news.... PMID- 25119447 TI - Dysphagia and associated risk factors following extubation in cardiovascular surgical patients. AB - Following cardiovascular (CV) surgery, prolonged mechanical ventilation of >48 h increases dysphagia frequency over tenfold: 51 % compared to 3-4 % across all durations. Our primary objective was to identify dysphagia frequency following CV surgery with respect to intubation duration. Our secondary objective was to explore characteristics associated with dysphagia across the entire sample. Using a retrospective design, we stratified all consecutive patients who underwent CV surgery in 2009 at our institution into intubation duration groups defined a priori: I (<= 12 h), II (>12 to <= 24 h), III (>24 to <= 48 h), and IV (>48 h). Eligible patients were >18 years old who survived extubation following coronary artery bypass alone or cardiac valve surgery. Patients who underwent tracheotomy were excluded. Pre-, peri-, and postoperative patient variables were extracted from a pre-existing database and medical charts by two blinded reviewers. Disagreements were resolved by consensus. Across the entire sample, multivariable logistic regression analysis determined independent predictors of dysphagia. Across the entire sample, dysphagia frequency was 5.6 % (51/909) but varied by group: I, 1 % (7/699); II, 8.2 % (11/134); III, 16.7 % (6/36); and IV, 67.5 % (27/40). Across the entire sample, the independent predictors of dysphagia included intubation duration in 12-h increments (p < 0.001; odds ratio [OR] 1.93, 95 % confidence interval [CI] 1.63-2.29) and age in 10-year increments (p = 0.004; OR 2.12, 95 % CI 1.27-3.52). Patients had a twofold increase in their odds of developing dysphagia for every additional 12 h with endotracheal intubation and for every additional decade in age. These patients should undergo post extubation swallow assessments to minimize complications. PMID- 25119448 TI - Water extracts from winery by-products as tobacco defense inducers. AB - Water extracts from winery by-products exhibited significant plant defense inducer properties. Experiments were conducted on three marc extracts containing various amounts of polyphenols and anthocyanins. Infiltration of red, white and seed grape marc extracts into tobacco leaves induced hypersensitive reaction-like lesions with cell death evidenced by Evans Blue staining. The infiltration zones and the surrounding areas revealed accumulation of autofluorescent compounds under UV light. Leaf infiltration of the three winery by-product extracts induced defense gene expression. The antimicrobial PR1, beta-1,3-glucanase PR2, and chitinase PR3 target genes were upregulated locally in tobacco plants following grape marc extract treatments. The osmotin PR5 transcripts accumulated as well in red marc extract treated-tobacco leaves. Overall, the winery by-product extracts elicited an array of plant defense responses making the grape residues a potential use of high value compounds. PMID- 25119449 TI - Effects of Cd, Co, Cu, Ni and Zn on asexual reproduction and early development of the tropical sea anemone Aiptasia pulchella. AB - Currently few studies present sub-lethal toxicity data for tropical marine species, and there are no routine toxicity tests using marine cnidarians. The symbiotic sea anemone Aiptasia pulchella has been identified as a useful species for ecotoxicological risk assessment, and would provide a tropical marine cnidarian representative. Chronic sub-lethal toxicity tests assessing the effects of 28-day trace metal exposure on asexual reproduction in A. pulchella were investigated, and concentration-dependant reductions in the number of offspring that were produced were evident for all metal exposures. Metal concentration estimates causing 50% reductions in the numbers of asexually-reproduced juveniles after 28-day exposures (28-day effect concentrations 50%: EC50s) were 14 ug/L for copper, 63 ug/L for zinc, 107 ug/L for cobalt, 145 ug/L for cadmium, and 369 ug/L for nickel. Slightly higher 28-day EC50s of 16 ug/L for copper, 192 ug/L for zinc, 172 ug/L for cobalt, 185 ug/L for cadmium, and 404 ug/L for nickel exposures and were estimated based on reductions in the total number of live developed and undeveloped offspring. These sensitive and chronic sub-lethal toxicity estimates help fill the knowledge gap related to metal effects on cnidarians over longer exposure periods, and this newly-developed bioassay may provide a much needed tool for ecotoxicological risk assessment relevant to tropical marine environments. PMID- 25119450 TI - Environmental stressors can enhance the development of community tolerance to a toxicant. AB - Ecosystems are subject to a combination of recurring anthropogenic and natural disturbances, such as climate change and pesticide exposure. Biological communities are known to develop tolerance to recurring disturbances due to successive changes at both the community and organismal levels. However, information on how additional stressors may affect the development of such community tolerance is scarce to date. We studied the influence of hydrological disturbance on the reaction of zooplankton communities to repeated insecticide pulses in outdoor microcosms. The communities were exposed to three successive pulses of the insecticide esfenvalerate (0.03, 0.3, and 3 ug/L) and to the gradual removal of water and its subsequent replacement over three cycles or to a constant water level. Except at the highest esfenvalerate concentration, the communities developed tolerance to the toxicant, as indicated by their decreasing reaction to subsequent insecticide applications, and this development was enhanced by hydrological disturbance. The pronounced decline of the key taxa Daphnia spp. through the combined action of the two stressors was identified as the main mechanism responsible for the increase in community tolerance under a fluctuating water level. Under a constant water level, the abundance of Daphnia spp. did not decrease significantly without the insecticide treatment, indicating that other mechanisms were responsible for the observed community tolerance. The present study shows that additional stressors can facilitate the development of community tolerance and that such facilitation is propagated through community level mechanisms. PMID- 25119451 TI - The imaging feature in capsule endoscopy on Maffucci syndrome with intestinal hemangioma. PMID- 25119452 TI - Combined application of clip and endoloop for the prevention of postpolypectomy complications in large pedunculated colonic polyps: a better choice. PMID- 25119453 TI - Cancer screenee cohort study of the National Cancer Center in South Korea. AB - The Cancer Screenee Cohort Study was first established in 2002 by the National Cancer Center in South Korea to investigate all possible risk factors related to cancers and to expand biological specimen banking for the development of effective methodologies for cancer detection, diagnosis, and prevention. As of July in 2014, total 41,105 participants were enrolled in this cohort. Data were collected via questionnaire, clinical examination, cancer screening, and biological specimen testing including blood, urine, and exfoliated cervical cells. The highest incidence was found to be thyroid cancer, according to a nested case-control study that was linked to the National Cancer Registry information as of December 31, 2011. Case-control, cross-sectional, and cohort studies have been published using these data since 2009. Diet and nutrition was the most published topic, followed by genetics, hepatitis B virus and liver cancer screening, methodologies, physical activity, obesity, metabolic syndrome, smoking and alcohol consumption, and blood type. Evidence from the Cancer Screenee Cohort Study is highly anticipated to reduce the burden of cancer in the Korean population and aid in the detection, diagnosis, and prevention of cancer. PMID- 25119454 TI - Prevalence and healthcare utilization of herpes zoster and postherpetic neuralgia in South Korea: disparity among patients with different immune statuses. AB - OBJECTIVES: Despite the clinical and epidemiological importance of herpes zoster (HZ) and postherpetic neuralgia (PHN), their disease and economic burden related to immune status has not been studied in South Korea. Our aim was to calculate the prevalence and rate of healthcare utilization related to HZ and PHN among Korean patients stratified by immune status. METHODS: This retrospective study used the Health Insurance Review and Assessment Service National Patients Sample (HIRA K-NPS) database, which includes all medical claims from January to December 2009 on a representative sample of the Korean population. HZ and PHN patients aged >= 50 years were categorized into three groups by immune status: severely immunocompromised group, moderately compromised group, and non-compromised group. The prevalence, disease-related healthcare utilization, and medical costs were compared across the three groups. RESULTS: We estimated that there were 312,136 HZ patients and 48,461 PHN patients >= 50 years in South Korea. The prevalence of HZ and PHN was 18.54 and 2.88 per 1,000 persons, respectively, and increased with deteriorating immune status. The number of outpatient visits and hospitalization rate among HZ patients were highest in the severely immunocompromised group (4.38% and 7.52%, respectively) and lowest in the non-compromised group (3.82% and 4.08%, respectively). The average medical cost per patient in the severe group was the highest (240 US dollars) and that of the non-compromised group was the lowest (161 US dollars). No parameters were significantly different among patients with PHN by immunity. CONCLUSIONS: HZ patients with severe immunodeficiency had a higher prevalence of HZ, more outpatient visits and hospitalizations, longer hospitalizations, and higher medical costs than their counterparts did. Efforts should be made to reduce the HZ-related burden of severely immunocompromised patients. PMID- 25119455 TI - Atrial fibrillation in end stage renal disease patients: influence of hemodialysis on P wave duration and atrial dimension. AB - BACKGROUND: Prevalence and incidence of atrial fibrillation (AF) are high in hemodialysis (HD) patients. Intra-atrial conduction velocity slowing plays an important role in AF onset. The aim of our study was to measure P wave duration (Pwd), expression of intra-atrial conduction velocity, in HD patients with and without a history of AF. METHODS: The study was performed in 47 end stage renal disease (ESRD) patients, subdivided into four groups: 19 patients within the first 6 months from starting HD therapy (HD1); the same patients studied 18 +/- 3 months later (HD2); patients with no history of AF and long dialytic age (HD3, n = 13); and patients with sinus rhythm but history of AF (HDAF, n = 15); and 18 healthy controls. In all patients P wave high resolution recording and electrolyte plasma values were obtained before and after a HD session, and atrial diameter was assessed by echocardiography. RESULTS: Patients with the shortest dialysis vintage showed the shortest Pwd [131.2 +/- 11.0 (HD1) vs. 139.8 +/- 11.7 (HD2), 142.1 +/- 7.2 (HD3), 152.3 +/- 15.0 (HDAF) ms; p < 0.05], while Pwd was prolonged in patients with AF history when compared to all other groups (p < 0.03). At multivariate analysis atrial dimension was independently related to Pwd (R = 0.40, p < 0.02). HD session induced a significant increase of Pwd (141 +/- 14.0-152 +/- 17.0 ms, p < 0.001), that was correlated to modifications of K(+) concentration (R = 0.8, p < 0.0001). CONCLUSIONS: HD therapy prolongs Pwd. HD patients with a history of AF have prolonged Pwd compared to patients without, suggesting that increased Pwd is a marker of AF risk in patients with ESRD. HD session acutely increases Pwd, creating conditions favoring AF onset. PMID- 25119456 TI - Central administration of C-X-C chemokine receptor type 4 antagonist alleviates the development and maintenance of peripheral neuropathic pain in mice. AB - AIM: To explore the roles of C-X-C chemokine receptor type 4 (CXCR4) in spinal processing of neuropathic pain at the central nervous system (CNS). METHODS: Peripheral neuropathic pain (PNP) induced by partial sciatic nerve ligation (pSNL) model was assessed in mice. Effects of a single intrathecal (central) administration of AMD3100 (intrathecal AMD3100), a CXCR4 antagonist, on pain behavior and pain-related spinal pathways and molecules in the L3-L5 spinal cord segment was studied compare to saline treatment. RESULTS: Rotarod test showed that intrathecal AMD3100 did not impair mice motor function. In pSNL-induced mice, intrathecal AMD3100 delayed the development of mechanical allodynia and reversed the established mechanical allodynia in a dose-dependent way. Moreover, intrathecal AMD3100 downregulated the activation of JNK1 and p38 pathways and the protein expression of p65 as assessed by western blotting. Real-time PCR test also demonstrated that substance P mRNA was decreased, while adrenomedullin and intercellular adhesion molecule mRNA was increased following AMD3100 treatment. CONCLUSION: Our results suggest that central (spinal) CXCR4 is involved in the development and maintenance of PNP and the regulation of multiple spinal molecular events under pain condition, implicating that CXCR4 would potentially be a therapeutic target for chronic neuropathic pain. PMID- 25119458 TI - A commentary on the disparate perspectives of clinical microbiologists and surgeons: Ad hoc antimicrobial use. AB - Prosthetic joints and other orthopedic implants have improved quality of life for patients world-wide and the use of such devices is increasing. However, while infection rates subsequent to associated surgery are relatively low (<3%), the consequences of incidence are considerable, encompassing morbidity (including amputation) and mortality in addition to significant social and economic costs. Emphasis, therefore, has been placed on mitigating microbial risk, with clinical microbiologists and surgeons utilizing rapidly evolving molecular laboratory techniques in detection and diagnosis of infection, which still occurs despite sophisticated patient management. Multidisciplinary approaches are regularly adopted to achieve this. In this commentary, we describe an unusual case of Actinomyces infection in total hip arthroplasty and, in that context, describe the perspectives of the clinical microbiology and surgical teams and how they contrasted. More specifically, this case demonstrates an ad hoc approach to structured eradication of biofilms and intracellular bacteria related to biomaterials, as reflected in early usage of linezolid. This is a complex topic and, as described in this case, such accelerated treatment can be effective. This commentary focuses on the merits of such inadvisable use of potent antimicrobials amid the risk of diminishing valuable antimicrobial efficacy, albeit resulting in desirable patient outcomes. PMID- 25119457 TI - Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model. AB - The development of noninvasive approaches to facilitate the regeneration of post traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808 nm LLLT at 8 J/cm(2) and a sciatic nerve crush injury group with or without 808 nm LLLT at 3, 8 or 15 J/cm(2). Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm(2) had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm(2). Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm(2). Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm(2) and 8 J/cm(2)) is capable of enhancing sciatic nerve regeneration following a crush injury. PMID- 25119463 TI - Does minimally-invasive pancreaticoduodenectomy have advantages over its open method? A meta-analysis of retrospective studies. AB - BACKGROUND: While more and more open procedures now routinely performed using laparoscopy, minimally invasive pancreaticoduodenectomy (MIPD) remains one of the most challenging abdominal procedures. Therefore, we carried out this meta analysis to evaluate whether MIPD is safe, feasible and worthwhile. METHODS: PubMed, EMBASE, and Cochrane Library were searched to identify studies published between January 1994 and November 2013 comparing MIPD with open pancreaticoduodenectomy (OPD). Intraoperative outcomes, oncologic safety, postoperative complications, and postoperative recovery were evaluated. RESULTS: 11 retrospective studies representing 869 patients (327 MIPDs, 542 OPDs) were included. MIPD was associated with a reduction in estimated blood loss (MD 361.93 ml, 95% CI -519.22 to -204.63 ml, p<0.001, I(2) = 94%), wound infection (OR 0.41, 95% CI 0.22 to 0.78, p = 0.007, I(2) = 0%), and hospital stay (MD -2.64 d, 95% CI -4.23 to -1.05 d, p = 0.001, I(2) = 78%). However, it brings longer operative time (MD 105 min, 95% CI 49.73 to 160.26 min, p<0.001, I(2) = 93%). There were no significant differences between the two procedures in likelihood of overall complications (p = 0.05), pancreatic fistula (PF) (p = 0.86), delayed gastric empting (DGE) (p = 0.96), positive surgical margins (p = 0.07), retrieval of lymph nodes (p = 0.48), reoperation (p = 0.16) and mortality (p = 0.64). CONCLUSIONS: Our results suggest that MIPD is currently safe, feasible and worthwhile. But considering the selection bias, complexity of MIPD and lack of long-term oncologic outcomes, we suggest it be performed in a high-volume pancreatic surgery center in selected patients. PMID- 25119464 TI - The pattern and loci of training-induced brain changes in healthy older adults are predicted by the nature of the intervention. AB - There is enormous interest in designing training methods for reducing cognitive decline in healthy older adults. Because it is impaired with aging, multitasking has often been targeted and has been shown to be malleable with appropriate training. Investigating the effects of cognitive training on functional brain activation might provide critical indication regarding the mechanisms that underlie those positive effects, as well as provide models for selecting appropriate training methods. The few studies that have looked at brain correlates of cognitive training indicate a variable pattern and location of brain changes--a result that might relate to differences in training formats. The goal of this study was to measure the neural substrates as a function of whether divided attentional training programs induced the use of alternative processes or whether it relied on repeated practice. Forty-eight older adults were randomly allocated to one of three training programs. In the single repeated training, participants practiced an alphanumeric equation and a visual detection task, each under focused attention. In the divided fixed training, participants practiced combining verification and detection by divided attention, with equal attention allocated to both tasks. In the divided variable training, participants completed the task by divided attention, but were taught to vary the attentional priority allocated to each task. Brain activation was measured with fMRI pre- and post training while completing each task individually and the two tasks combined. The three training programs resulted in markedly different brain changes. Practice on individual tasks in the single repeated training resulted in reduced brain activation whereas divided variable training resulted in a larger recruitment of the right superior and middle frontal gyrus, a region that has been involved in multitasking. The type of training is a critical factor in determining the pattern of brain activation. PMID- 25119465 TI - Functional balance between the hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 HA D222 variants. AB - D222G/N substitutions in A(H1N1)pdm09 hemagglutinin may be associated with increased binding of viruses causing low respiratory tract infections and human pathogenesis. We assessed the impact of such substitutions on the balance between hemagglutinin binding and neuraminidase cleavage, viral growth and in vivo virulence.Seven viruses with differing polymorphisms at codon 222 (2 with D, 3 G, 1 N and 1 E) were isolated from patients and characterized with regards hemagglutinin binding affinity (Kd) to alpha-2,6 sialic acid (SAalpha-2,6) and SAalpha-2,3 and neuraminidase enzymatic properties (Km, Ki and Vmax). The hemagglutination assay was used to quantitatively assess the balance between hemagglutinin binding and neuraminidase cleavage. Viral growth properties were compared in vitro in MDCK-SIAT1 cells and in vivo in BALB/c mice. Compared with D222 variants, the binding affinity of G222 variants was greater for SAalpha-2,3 and lower for SAalpha-2,6, whereas that of both E222 and N222 variants was greater for both SAalpha-2,3 and SAalpha-2,6. Mean neuraminidase activity of D222 variants (16.0 nmol/h/10(6)) was higher than that of G222 (1.7 nmol/h/10(6) viruses) and E/N222 variants (4.4 nmol/h/10(6) viruses). The hemagglutination assay demonstrated a deviation from functional balance by E222 and N222 variants that displayed strong hemagglutinin binding but weak neuraminidase activity. This deviation impaired viral growth in MDCK-SIAT1 cells but not infectivity in mice. All strains but one exhibited low infectious dose in mice (MID50) and replicated to high titers in the lung; this D222 strain exhibited a ten-fold higher MID50 and replicated to low titers. Hemagglutinin-neuraminidase balance status had a greater impact on viral replication than hemagglutinin affinity strength, at least in vitro, thus emphasizing the importance of an optimal balance for influenza virus fitness. The mouse model is effective in assessing binding to SAalpha-2,3 but cannot differentiate SAalpha-2,3- from SAalpha-2,6- preference, nor estimate the hemagglutinin-neuraminidase balance in A(H1N1)pdm09 strains. PMID- 25119468 TI - Combining XCO2 measurements derived from SCIAMACHY and GOSAT for potentially generating global CO2 maps with high spatiotemporal resolution. AB - Global warming induced by atmospheric CO2 has attracted increasing attention of researchers all over the world. Although space-based technology provides the ability to map atmospheric CO2 globally, the number of valid CO2 measurements is generally limited for certain instruments owing to the presence of clouds, which in turn constrain the studies of global CO2 sources and sinks. Thus, it is a potentially promising work to combine the currently available CO2 measurements. In this study, a strategy for fusing SCIAMACHY and GOSAT CO2 measurements is proposed by fully considering the CO2 global bias, averaging kernel, and spatiotemporal variations as well as the CO2 retrieval errors. Based on this method, a global CO2 map with certain UTC time can also be generated by employing the pattern of the CO2 daily cycle reflected by Carbon Tracker (CT) data. The results reveal that relative to GOSAT, the global spatial coverage of the combined CO2 map increased by 41.3% and 47.7% on a daily and monthly scale, respectively, and even higher when compared with that relative to SCIAMACHY. The findings in this paper prove the effectiveness of the combination method in supporting the generation of global full-coverage XCO2 maps with higher temporal and spatial sampling by jointly using these two space-based XCO2 datasets. PMID- 25119469 TI - Targeting strategies for delivery of anti-HIV drugs. AB - Human Immunodeficiency Virus (HIV) infection remains a significant cause of mortality globally. Though antiretroviral therapy has significantly reduced AIDS related morbidity and mortality, there are several drawbacks in the current therapy, including toxicity, drug-drug interactions, development of drug resistance, necessity for long-term drug therapy, poor bio-availability and lack of access to tissues and reservoirs. To circumvent these problems, recent anti HIV therapeutic research has focused on improving drug delivery systems through drug delivery targeted specifically to host cells infected with HIV or could potentially get infected with HIV. In this regard, several surface molecules of both viral and host cell origin have been described in recent years, that would enable targeted drug delivery in HIV infection. In the present review, we provide a comprehensive overview of the need for novel drug delivery systems, and the successes and challenges in the identification of novel viral and host-cell molecules for the targeted drug delivery of anti-HIV drugs. Such targeted anti retroviral drug delivery approaches could pave the way for effective treatment and eradication of HIV from the body. PMID- 25119466 TI - Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer cells: involvement of PPARgamma. AB - Trans-3,5-dimethoxy-4'-hydroxystilbene (PTER), a natural dimethylated analog of resveratrol, preferentially induces certain cancer cells to undergo apoptosis and could thus have a role in cancer chemoprevention. Peroxisome proliferator activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, is a ligand-dependent transcription factor whose activation results in growth arrest and/or apoptosis in a variety of cancer cells. Here we investigated the potential of PTER-isothiocyanate (ITC) conjugate, a novel class of hybrid compound (PTER-ITC) synthesized by appending an ITC moiety to the PTER backbone, to induce apoptotic cell death in hormone-dependent (MCF-7) and independent (MDA-MB-231) breast cancer cell lines and to elucidate PPARgamma involvement in PTER-ITC action. Our results showed that when pre-treated with PPARgamma antagonists or PPARgamma siRNA, both breast cancer cell lines suppressed PTER-ITC-induced apoptosis, as determined by annexin V/propidium iodide staining and cleaved caspase-9 expression. Furthermore, PTER-ITC significantly increased PPARgamma mRNA and protein levels in a dose-dependent manner and modulated expression of PPARgamma-related genes in both breast cancer cell lines. This increase in PPARgamma activity was prevented by a PPARgamma specific inhibitor, in support of our hypothesis that PTER-ITC can act as a PPARgamma activator. PTER-ITC-mediated upregulation of PPARgamma was counteracted by co-incubation with p38 MAPK or JNK inhibitors, suggesting involvement of these pathways in PTER-ITC action. Molecular docking analysis further suggested that PTER-ITC interacted with 5 polar and 8 non-polar residues within the PPARgamma ligand-binding pocket, which are reported to be critical for its activity. Collectively, our observations suggest potential applications for PTER-ITC in breast cancer prevention and treatment through modulation of the PPARgamma activation pathway. PMID- 25119470 TI - Single nucleotide polymorphisms other than factor V Leiden are associated with coagulopathy and osteonecrosis of the femoral head in Chinese patients. AB - Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (87.6%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.62; 95% confidence interval: 1.44 14.8) of having coagulation abnormalities than did those without the mutation (wild-type) (chi(2) p = 0.006). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head. PMID- 25119471 TI - Longitudinal evaluation of the metabolic response of a tumor xenograft model to single fraction radiation therapy using magnetic resonance spectroscopy. AB - Proton magnetic resonance spectroscopy (MRS) was used to evaluate the metabolic profile of human glioblastoma multiform brain tumors grown as xenografts in nude mice before, and at multiple time points after single fraction radiation therapy. Tumors were grown over the thigh in 16 mice in this study, of which 5 served as untreated controls and 11 had their tumors treated to 800 cGy with 200 kVp x rays. Spectra were acquired within 24 h pre-treatment, and then at 3, 7 and 14 d post-treatment using a 9.4 T animal magnetic resonance (MR) system. For the untreated control tumors, spectra (1-2 per mouse) were acquired at different stages of tumor growth. Spectra were obtained with the PRESS pulse sequence using a 3 * 3 * 3 mm(3) voxel. Analysis was performed with the LCModel software platform. Six metabolites were profiled for this analysis: alanine (Ala), myo inositol (Ins), taurine (Tau), creatine and phosphocreatine (Cr + PCr), glutamine and glutamate (Glu + Gln), and total choline (glycerophosphocholine + phosphocholine) (GPC + PCh). For the treated cohort, most metabolite/water concentration ratios were found to decrease in the short term at 3 and 7 d post treatment, followed by an increase at 14 d post-treatment toward pre-treatment values. The lowest concentrations were observed at 7 d post-treatment, with magnitudes (relative to pre-treatment concentration ratios) of: 0.42 +/- 24.6% (Ala), 0.43 +/- 15.3% (Ins), 0.68 +/- 27.9% (Tau), 0.52 +/- 14.6% (GPC+PCh), 0.49 +/- 21.0% (Cr + PCr) and 0.78 +/- 24.5% (Glu + Gln). Control animals did not demonstrate any significant correlation between tumor volume and metabolite concentration, indicating that the observed kinetics were the result of the therapeutic intervention. We have demonstrated the feasibility of using MRS to follow multiple metabolic markers over time for the purpose of evaluating therapeutic response of tumors to radiation therapy. This study provides supporting evidence that metabolite/water concentration ratios have the potential to be used as biomarkers for the assessment of the response to therapy. PMID- 25119472 TI - Prevalence of skin problems and leg ulceration in a sample of young injecting drug users. AB - BACKGROUND: Drug users suffer harm from the injecting process, and clinical services are reporting increasing numbers presenting with skin-related problems such as abscesses and leg ulcers. Skin breakdown can lead to long-term health problems and increased service costs and is often the first indication of serious systemic ill health. The extent of skin problems in injecting drug users has not previously been quantified empirically, and there is a dearth of robust topical literature. Where skin problems have been reported, this is often without clear definition and generic terms such as 'soft tissue infection' are used which lack specificity. The aim of this study was to identify the range and extent of skin problems including leg ulceration in a sample of injecting drug users. Definitions of skin problems were developed and applied to descriptions from drug users to improve rigour. METHODS: Data were collected in needle exchanges and methadone clinics across Glasgow, Scotland, from both current and former drug injectors using face-to-face interviews. RESULTS: Two hundred participants were recruited, of which 74% (n = 148) were males and 26% (n = 52) were females. The age range was 21-44 years (mean 35 years). Just under two thirds (64%, n = 127) were currently injecting or had injected within the last 6 months, and 36% (n = 73) had previously injected and had not injected for more than 6 months.Sixty per cent (n = 120) of the sample had experienced a skin problem, and the majority reported more than one problem. Most common were abscesses, lumps, track marks and leg ulcers. Fifteen per cent (n = 30) of all participants reported having had a leg ulcer. CONCLUSIONS: This is an original empirical study which demonstrated unique findings of a high prevalence of skin disease (60%) and surprisingly high rates of leg ulceration (15%). Skin disease in injecting drug users is clearly widespread. Leg ulceration in particular is a chronic recurring condition that is costly to treat and has long-term implications for drug users and services caring for current or former injectors long after illicit drug use has ceased. PMID- 25119473 TI - Unveiling viral-host interactions within the 'microbial dark matter'. AB - Viruses control natural microbial communities. Identification of virus-host pairs relies either on their cultivation or on metagenomics and tentative assignment based on genomic signatures. Both approaches have severe drawbacks when aiming to target such pairs within the uncultured majority. Here we present an unambiguous way to assign viruses to hosts that does not rely on any previous information about either of them nor requires their cultivation. First, genomic contents of individual cells present in an environmental sample are retrieved by means of single-cell genomic technologies. Then, individual cell genomes are hybridized against a set of individual viral genomes from the same sample, previously immobilized on a microarray. Infected cells will yield positive hybridization as they carry viral genomes, which can be then sequenced and characterized. Using this method, we pinpoint viruses infecting the ubiquitous hyperhalophilic Nanohaloarchaeota, included in the so-called 'microbial dark matter' (the uncultured fraction of the microbial world). PMID- 25119475 TI - [The relevance of the trace elements zinc and iron in the milk fever disease of cattle]. AB - OBJECTIVE: The aim of this study was to analyse the concentrations of Zn and Fe as well as their relationships to metabolic parameters in milk fever cows. MATERIAL AND METHODS: A total of 195 Simmental cows, downer cows and clinically healthy control animals were divided into five groups: a) control group (CG, n = 21), b) all cows with milk fever (MF) (n = 174), c) MF cows without additional diseases (n = 145), d) cows with MF and mastitis (n = 10) and e) cows with retained placenta or endometritis (n = 19). Selenium (Se), zinc (Zn), iron (Fe), calcium (Ca), inorganic phosphorus (Pi), tumour necrosis factor alpha (TNFalpha), haptoglobin (Hp), antioxidants (Trolox Equivalent Antioxidative Capacity: TEAC), non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), bilirubin, urea, creatinine, glucose, cholesterol, gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) were analysed in the blood serum. RESULTS: The concentrations of Zn, Fe, Ca, Pi and TEAC were lower in groups b) to e) whereas Hp was higher than in the CG (p <= 0.05). In group c), lower Ca and Pi concentrations were found when compared to groups d) and e) (p <= 0.05). In group e), Zn concentrations were significantly lower than in group c) (p <= 0.05). Zn was negatively correlated with K (CG) and positively correlated with TEAC, Cu, Mn and Fe (groups b and c) and with Mn (group e) (p <= 0.05). Fe was positively correlated with Ca (group c), Pi (group c), K (groups b and c) and Mg (groups b-d) as well as with Zn, Cu and Se (groups b and c) (p <= 0.05). In groups b) and c), TNFalpha was increased and negatively correlated with Fe (p <= 0.05). AP activity in groups b) and e) was lower than in the CG (p <= 0.05). CONCLUSION: These results and literature data support the hypothesis that Zn and Fe could be engaged in bone metabolism and be involved in the pathogenesis of MF. The concentrations of Hp and TEAC support this interpretation. Control of the Zn and Fe status of cows and Zn supplementation should be included in the prevention and advanced therapy of MF. PMID- 25119474 TI - Plasma B-type natriuretic peptide is a useful tool for assessing coronary heart disease risk in a Japanese general population. AB - B-type natriuretic peptide (BNP) has been reported to be associated with cardiovascular prognosis in a community-based population. In addition, accumulation of individual cardiovascular risk factors is important in predicting an individual's risk of future cardiovascular disease. However, there have been few reports showing that BNP is a comprehensive marker of the accumulation of cardiovascular risk factors. We studied 1530 community-dwelling subjects without obvious heart diseases or renal dysfunction (mean age 62 +/- 15 years; 569 men and 961 women) who participated in an annual health checkup in a rural Japanese community. Coronary heart disease (CHD) risk was estimated, and patients were placed into the following three groups based on the Framingham function: low risk, moderate risk and high risk. The prevalence of moderate- and high-risk subjects for CHD rose in both genders with increasing plasma BNP levels. The area under the receiver operating characteristic curve showed a modest ability of plasma BNP levels to detect these subjects (0.755 and 0.700 for men and women, respectively). The optimal thresholds for the identification of subjects with moderate- and high-risk disease were BNP concentrations of 12.0 and 22.0 pg ml( 1), with sensitivities of 70% and 66% and specificities of 71% and 63% for men and women, respectively. In conclusion, subjects with high plasma BNP levels were at higher risk for CHD in a population without obvious heart disease or renal dysfunction. PMID- 25119476 TI - [Blood serum vitamin B12 concentration in dairy cows during early lactation]. AB - OBJECTIVE: To describe the characteristics of the blood serum vita- min B12 concentration of dairy cows post partum (p. p.) and to investigate its relationship with metabolic parameters, the erythrogram and the health status of the cows. MATERIAL AND METHODS: Blood samples from 157 Holstein-Friesian-cows were obtained for metabolic analysis at 2-6 days p. p. and at 4-5 weeks p. p. In addition, clinical findings were compiled to evaluate the health status (healthy/morbid). RESULTS: In all animals a decline in the vitamin B12 concentration (p <= 0.05) at 4 weeks p. p. was observed. Animals of both groups (healthy/morbid) had higher values for the erythrocyte count, haematocrit and haemoglobin concentration 2-6 days p. p. when compared to 4 weeks p. p. In all cows, gamma-glutamyl transferase (GGT) activity was closely correlated to the vitamin B12 concentration (p <= 0.01). Furthermore, all animals displayed elevated concentrations of beta-hydroxybutyrate, non-esterified fatty acids and bilirubin (p <= 0.05) at 2-6 days p. p. as a consequence of partus-dependent increased lipolysis. There was a smaller decrease in the vitamin B12 concentration in the morbid cows compared to the healthy cows (p <= 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: The vitamin B12 concentration is significantly dynamic during lactation and displays a close relationship with the GGT activity and the parameters of energy metabolism. Vitamin B12 may act as an indicator for increased lipolysis and cholestasis. Higher vitamin B12 concentrations may indicate clinical problems. A relationship with haematopoiesis is recognizable from the red cell readings. Decreasing red cell readings associated with reduced performance could be related to a low vitamin B12 concentration. The close correlations of vitamin B12 with GGT activity and bilirubin concentration may indicate cholestatic metabolic stress in dairy cows at blood serum concentrations >= 227 ng/l (3rd quartile 2-6 days p. p. healthy group). Morbid cows can already be identified at the subclinical stage. PMID- 25119477 TI - [Energy intake and body weight development of Warmblood foals that changed stud at weaning]. AB - OBJECTIVE: This study investigated the energy requirements of Warmblood foals with a change of the stud at weaning. MATERIAL AND METHODS: Nine colts purchased at weaning participated in the study aged approximately 6 months to 1 year. They were transported to the stud by their breeders either having been separated from their dams in their home stable or upon arrival at the stud. The foals were offered a late first cut of haylage, oats and foal starter feed. To ensure individual feeding of concentrates, the foals were tethered twice daily. The total combined haylage intake of all foals per day was recorded. Individual concentrate intake, body weight and body condition score (BCS) were documented at 4-week intervals. RESULTS: The total energy intake was 74 MJ digestible energy (68 MJ metabolisable energy) per animal per day. The foals had been delivered at the stud with a comparably low body weight (285 +/- 30 kg) and BCS (4.2 +/- 0.4 on a scale from 1 to 9). At the end of the study, aged 319 +/- 22 days, they attained an average body weight of 326 +/- 24 kg and a BCS of 4.2 +/- 0.4. The energy intake of the foals of this study was higher and their body weight development slower than in foals of a parallel study, which were born and raised in the stud and therefore exposed to less stressful weaning conditions. CONCLUSION AND CLINICAL RELEVANCE: Foals with a comparatively low body weight and BCS at weaning in combination with further stressors need considerably more energy than foals that undergo less stressful weaning conditions. PMID- 25119478 TI - [New drugs for horses and production animals in 2013]. AB - In 2013, only one newly developed active pharmaceutical ingredient for horses and food-producing animals was released on the German market for veterinary drug products. The ionophore monensin from the group of polyether antibiotics is now available as an orally administered continuous release intraruminal device for cattle (Kexxtone(r)). Furthermore, two established veterinary active pharmaceutical ingredients are available for additional species: The antibiotic amoxicillin (Suramox(r)) is also authorized for ducks and turkeys and the dissociative anesthetic ketamine is now authorized for sheep, goats and dairy cattle. Additionally, one veterinary drug with a new pharmaceutical form as well as one product with a new strength have been launched on the market for veterinary drugs for horses and food producing animals. PMID- 25119479 TI - [Resection of a carpal bone row in a Pustertaler Sprinze cow with chronic purulent arthritis of the carpal joint and osteomyelitis]. AB - This case report describes the clinical and radiographic findings and the surgical treatment of a serofibrinous arthritis of the antebrachiocarpal joint and of a chronic purulent arthritis of the intercarpal and carpometacarpal joints with osteomyelitis of the distal carpal bones and subchondral osteomyelitis of the proximal metacarpal bones in a cow of the breed "Pustertaler Sprinze". The therapy comprised an arthrotomy of both joint spaces and the resection of the distal row of the carpal bones. The right forelimb had been immobilised for 70 days by a full limb cast. After this period, radiographs revealed an ob- vious ankylosis of the carpal joint, and the cow showed only a slight lameness. Six years postoperatively this cow was still in the herd and had produced six calves. PMID- 25119480 TI - [Tuberculosis in cattle - surprisingly re-emerging or continuously present?]. AB - Tuberculosis in cattle, caused by Mycobacterium (M.) bovis/M. caprae, is globally one of the most important zoonotic diseases in cattle. It was widespread in Germany until the second half of the 20th century. Due to the effective control and eradication campaigns in Germany, the epidemic was almost eradicated. Consequently, Germany was regarded as essentially tuberculosis free since the end of 1961 (West) and the end of 1978 (East). By declaring the unified Germany "officially free of tuberculosis" (OTF) in 1996, freedom from tuberculosis was officially ratified by the European Commission. The prerequisite was the detection of tuberculosis in less than 0.1% of the cattle holdings per year in Germany. This status has been steadily maintained hitherto, thus resulting in some loss of awareness of bovine tuberculosis by veterinarians, farmers and the public over many decades. After 1996, the number of notified outbreaks had been on average less than 10 per 200,000 cattle holdings per year for many years. It was the year 2008 when the numbers increased. Based in part on subsequently enhanced ante mortem testing efforts, 46 outbreaks were notified in 2013. Bavaria and Lower Saxony were the federal states with the highest number of cases. Consequently, the national tuberculosis regulation was revised in 2009, 2012 and 2013 to form the basis for a modification of tuberculosis surveillance. Regionally, an improvement of the control strategy was considered necessary. In addition to the traditionally applied examination and detection methods of the tuberculin skin test (ante mortem) and bacteriological culture (post mortem), the gamma-interferon-release assay (ante mortem) and the molecular detection of the causative pathogen (post mortem) were introduced into the official collection of recommended methods. Consequently, the diagnostic procedure of tuberculosis has been accelerated. However, in many cases the increase in the range of available test systems did not increase the ease in the interpretation of results. PMID- 25119481 TI - Emerging issues in translating laboratory experiments to applications for society. PMID- 25119483 TI - Non invasive monitoring in mechanically ventilated pediatric patients. AB - Cardiopulmonary monitoring is a key component in the evaluation and management of critically ill patients. Clinicians typically rely on a combination of invasive and non-invasive monitoring to assess cardiac output and adequacy of ventilation. Recent technological advances have led to the introduction: of continuous non invasive monitors that allow for data to be obtained at the bedside of critically ill patients. These advances help to identify hemodynamic changes and allow for interventions before complications occur. In this manuscript, we highlight several important methods of non-invasive cardiopulmonary monitoring, including capnography, transcutaneous monitoring, pulse oximetry, and near infrared spectroscopy. PMID- 25119482 TI - VirtualSpectrum, a tool for simulating peak list for multi-dimensional NMR spectra. AB - NMR spectroscopy is a widely used technique for characterizing the structure and dynamics of macromolecules. Often large amounts of NMR data are required to characterize the structure of proteins. To save valuable time and resources on data acquisition, simulated data is useful in the developmental phase, for data analysis, and for comparison with experimental data. However, existing tools for this purpose can be difficult to use, are sometimes specialized for certain types of molecules or spectra, or produce too idealized data. Here we present a fast, flexible and robust tool, VirtualSpectrum, for generating peak lists for most multi-dimensional NMR experiments for both liquid and solid state NMR. It is possible to tune the quality of the generated peak lists to include sources of artifacts from peak overlap, noise and missing signals. VirtualSpectrum uses an analytic expression to represent the spectrum and derive the peak positions, seamlessly handling overlap between signals. We demonstrate our tool by comparing simulated and experimental spectra for different multi-dimensional NMR spectra and analyzing systematically three cases where overlap between peaks is particularly relevant; solid state NMR data, liquid state NMR homonuclear (1)H and (15)N-edited spectra, and 2D/3D heteronuclear correlation spectra of unstructured proteins. We analyze the impact of protein size and secondary structure on peak overlap and on the accuracy of structure determination based on data of different qualities simulated by VirtualSpectrum. PMID- 25119484 TI - In vitro conversion of vinyl to formyl groups in naturally occurring chlorophylls. AB - The chemical structural differences distinguishing chlorophylls in oxygenic photosynthetic organisms are either formyl substitution (chlorophyll b, d, and f) or the degree of unsaturation (8-vinyl chlorophyll a and b) of a side chain of the macrocycle compared with chlorophyll a. We conducted an investigation of the conversion of vinyl to formyl groups among naturally occurring chlorophylls. We demonstrated the in vitro oxidative cleavage of vinyl side groups to yield formyl groups through the aid of a thiol-containing compound in aqueous reaction mixture at room temperature. Heme is required as a catalyst in aqueous solution but is not required in methanolic reaction mixture. The conversion of vinyl- to formyl- groups is independent of their position on the macrocycle, as we observed oxidative cleavages of both 3-vinyl and 8-vinyl side chains to yield formyl groups. Three new chlorophyll derivatives were synthesised using 8-vinyl chlorophyll a as substrate: 8-vinyl chlorophyll d, [8-formyl]-chlorophyll a, and [3,8-diformyl]-chlorophyll a. The structural and spectral properties will provide a signature that may aid in identification of the novel chlorophyll derivatives in natural systems. The ease of conversion of vinyl- to formyl- in chlorophylls demonstrated here has implications regarding the biosynthetic mechanism of chlorophyll d in vivo. PMID- 25119485 TI - Unique odd-chain polyenoic phospholipid fatty acids present in chytrid fungi. AB - Chytrid fungi are ubiquitous components of aquatic and terrestrial ecosystems yet they remain understudied. To investigate the use of phospholipid fatty acids as phenotypic characteristics in taxonomic studies and biomarkers for ecological studies, 18 chytrid fungi isolated from soil to freshwater samples were grown in defined media and their phospholipid fatty acid profile determined. Gas chromatographic/mass spectral analysis indicated the presence of fatty acids typically associated with fungi, such as 16:1(n-7), 16:0, 18:2(n-6), 18:3(n-3) 18:1(n-9), and 18:0, as well as, a number of odd-chain length fatty acids, including two polyunsaturated C-17 fatty acids. Conversion to their 3 pyridylcarbinol ester facilitated GC-MS determination of double-bond positions and these fatty acid were identified as 6,9-17:2 [17:2(n-8)] and 6,9,12-17:3 [17:3(n-5)]. To the best of our knowledge, this is the first report of polyunsaturated C-17 fatty acids isolated from the phospholipids of chytrid fungi. Cluster analysis of PLFA profiles showed sufficient correlation with chytrid phylogeny to warrant inclusion of lipid analysis in species descriptions and the presence of several phospholipid fatty acids of restricted phylogenetic distributions suggests their usefulness as biomarkers for ecological studies. PMID- 25119487 TI - Expression of genes controlling unsaturated fatty acids biosynthesis and oil deposition in developing seeds of Sacha inchi (Plukenetia volubilis L.). AB - Sacha inchi (Plukenetia volubilis L., Euphorbiaceae) seed oil is rich in alpha linolenic acid, a kind of n-3 fatty acids with many health benefits. To discover the mechanism underlying alpha-linolenic acid accumulation in sacha inchi seeds, preliminary research on sacha inchi seed development was carried out from one week after fertilization until maturity, focusing on phenology, oil content, and lipid profiles. The results suggested that the development of sacha inchi seeds from pollination to mature seed could be divided into three periods. In addition, investigations on the effect of temperature on sacha inchi seeds showed that total oil content decreased in the cool season, while unsaturated fatty acid and linolenic acid concentrations increased. In parallel, expression profiles of 17 unsaturated fatty acid related genes were characterized during seed development and the relationships between gene expression and lipid/unsaturated fatty acid accumulation were discussed. PMID- 25119486 TI - Dietary lipid intake only partially influences variance in serum phospholipid fatty acid composition in adolescents: impact of other dietary factors. AB - The present study aimed to assess the correlation between food and fatty acid (FA) intake and the serum phospholipid (PL) FA status in European adolescents and explored the percentage of variation in serum PL FA that could be attributed to dietary habits. Participants included 528 adolescents recruited in the HELENA Study. Dietary intake was assessed by two, self-administered, non-consecutive 24 h recalls. PL FA concentrations were measured in fasting venous serum samples. Reduced rank regressions were applied to examine the combined effect of food intakes. Results indicated that the variance in serum PL FA in adolescents, that could be explained by diet varied from 7.0% for MUFA to 14.2% for n-3FA. The variance in the long-chain n-3FA was mainly explained by fish intake but also by coffee and tea consumption. In conclusion this study indicated that dietary intake influences the serum PL FA status to a limited amount but that also other factors interfere. However, dietary intake is important as it is among those factors that could be modified. Furthermore, the results suggest that the overall dietary habits should be considered instead of only the consumption of single foods or nutrients, as the medium of the food or concomitant intake of foods and nutrients might interact and as such influence absorption or metabolism. PMID- 25119488 TI - What are the factors that interplay from normal pregnancy to near miss maternal morbidity in a Nigerian tertiary health care facility? AB - Researchers in Nigeria examined the epidemiological characteristics and factors associated with maternal outcomes using a mixed method approach: a prospective case control study design involving 375 pregnant women who received maternal care from a tertiary facility and in-depth interviews reporting the experience of near miss survivors. A generalized ordered logit model was used to generate the estimates of partial proportional odds ratios (and 95% confidence intervals) across categories of the outcome variable. Factors strongly associated with maternal morbidity were late referral of women, presence of complications at booking antenatal visits, low birth weight, and severe birth asphyxia. The nearmiss women were further characterized, and a low proportion (25%) had organ dysfunction or failure. The challenge of such diagnoses in resource-constrained settings raises questions about the appropriateness of using organ dysfunction criteria in developing countries. PMID- 25119491 TI - Ebola--underscoring the global disparities in health care resources. PMID- 25119490 TI - Supporting cancer patients in illness management: usability evaluation of a mobile app. AB - BACKGROUND: Mobile phones and tablets currently represent a significant presence in people's everyday lives. They enable access to different information and services independent of current place and time. Such widespread connectivity offers significant potential in different app areas including health care. OBJECTIVE: Our goal was to evaluate the usability of the Connect Mobile app. The mobile app enables mobile access to the Connect system, an online system that supports cancer patients in managing health-related issues. Along with symptom management, the system promotes better patient-provider communication, collaboration, and shared decision making. The Connect Mobile app enables access to the Connect system over both mobile phones and tablets. METHODS: The study consisted of usability tests of a high fidelity prototype with 7 cancer patients where the objectives were to identify existing design and functionality issues and to provide patients with a real look-and-feel of the mobile system. In addition, we conducted semistructured interviews to obtain participants' feedback about app usefulness, identify the need for new system features and design requirements, and measure the acceptance of the mobile app and its features within everyday health management. RESULTS: The study revealed a total of 27 design issues (13 for mobile apps and 14 for tablet apps), which were mapped to source events (ie, errors, requests for help, participants' concurrent feedback, and moderator observation). We also applied usability heuristics to identify violations of usability principles. The majority of violations were related to enabling ease of input, screen readability, and glanceability (15 issues), as well as supporting an appropriate match between systems and the real world (7 issues) and consistent mapping of system functions and interactions (4 issues). Feedback from participants also showed the cancer patients' requirements for support systems and how these needs are influenced by different context-related factors, such as type of access terminal (eg, desktop computer, tablet, mobile phone) and phases of illness. Based on the observed results, we proposed design and functionality recommendations that can be used for the development of mobile apps for cancer patients to support their health management process. CONCLUSIONS: Understanding and addressing users' requirements is one of the main prerequisites for developing useful and effective technology-based health interventions. The results of this study outline different user requirements related to the design of the mobile patient support app for cancer patients. The results will be used in the iterative development of the Connect Mobile app and can also inform other developers and researchers in development, integration, and evaluation of mobile health apps and services that support cancer patients in managing their health related issues. PMID- 25119492 TI - Hiwi facilitates chemoresistance as a cancer stem cell marker in cervical cancer. AB - Hiwi, also named PiwiL1, is a human homologue of the Piwi family which is associated with stem cells and is overexpressed in several types of cancers. In the present study, we aimed to investigate the role of Hiwi in cervical carcinogenesis. Immunochemical analysis showed a significantly higher frequency of Hiwi staining in high-grade squamous intraepithelial lesions (HSILs) and cervical cancer tissues when comparing with the frequency in normal cervices. Particularly, Hiwi staining was restricted to basal cells of the normal cervix and was associated with the progression of cervical cancer and chemotherapy resistance. We further found that ectopic Hiwi increased the chemical resistance in SiHa cells, and silencing of Hiwi in HeLa cells decreased the cell viability. In addition, as a cancer stem cell marker, Hiwi promoted the tumorsphere formation in vitro and tumorigenicity in vivo and elevated the expression of several stem cell self-renewal-associated transcription factors, in spite of inhibited the proliferation. These results suggest that Hiwi may participate in the carcinogenesis of cervical cancer and may be a potential therapeutic target molecule for cervical cancers. PMID- 25119493 TI - Bisphenol A modulates colorectal cancer protein profile and promotes the metastasis via induction of epithelial to mesenchymal transitions. AB - More and more evidences indicate that endocrine disruptor chemicals such as bisphenol A (BPA) can act as carcinogens and enhance susceptibility to tumorigenesis. Although the gut is in direct contact with orally ingested BPA, effects of BPA on occurrence and development of colorectal cancer remain an unexplored endpoint. Colorectal cancer SW480 cells treated with nanomolar (10(-8) M) or greater (10(-5) M) concentrations of BPA were compared with responses of a control group. Proteomic study revealed that more than 56 proteins were modulated following exposure to BPA, which are relevant to structure, motility and proliferation of cells, production of ATP, oxidative stress, and protein metabolism. Further studies revealed that BPA increased migration and invasion and triggered transformations from epithelial to mesenchymal transitions (EMTs) of colorectal cancer cells, which was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin with a concomitant decrease of E-cadherin. Accordingly, BPA treatment increased the expression of transcription factor Snail. Furthermore, signal AKT/GSK-3beta mediated stabilization of Snail is involved during BPA-induced EMT of colon cancer cells. Our study first demonstrated that the xenoestrogen BPA at nanomolar and greater concentrations modulates the protein profiles and promotes the metastasis of colorectal cancer cells via induction of EMT. PMID- 25119495 TI - Doctor-patient/family relationships: current status and projections for the future. PMID- 25119494 TI - Biology of ferritin in mammals: an update on iron storage, oxidative damage and neurodegeneration. AB - Iron is an abundant transition metal that is essential for life, being associated with many enzyme and oxygen carrier proteins involved in a variety of fundamental cellular processes. At the same time, the metal is potentially toxic due to its capacity to engage in the catalytic production of noxious reactive oxygen species. The control of iron availability in the cells is largely dependent on ferritins, ubiquitous proteins with storage and detoxification capacity. In mammals, cytosolic ferritins are composed of two types of subunits, the H and the L chain, assembled to form a 24-mer spherical cage. Ferritin is present also in mitochondria, in the form of a complex with 24 identical chains. Even though the proteins have been known for a long time, their study is a very active and interesting field yet. In this review, we will focus our attention to mammalian cytosolic and mitochondrial ferritins, describing the most recent advancement regarding their storage and antioxidant function, the effects of their genetic mutations in human pathology, and also the possible involvement in non-iron related activities. We will also discuss recent evidence connecting ferritins and the toxicity of iron in a set of neurodegenerative disorder characterized by focal cerebral siderosis. PMID- 25119496 TI - Peer victimization, caregiver restriction of food intake, and degree of overweight in youth. AB - OBJECTIVE: Although caregiver restriction of child food intake is a common weight control strategy, factors that make a caregiver more likely to engage in restriction have not been fully explored. This study examined the relations between child weight, peer victimization, and restriction. Peer victimization was expected to serve as a mechanism through which child weight was associated with restriction. METHOD: Two hundred fourteen youth (6-17 yr) were recruited from pediatric primary care clinics in the South. Youth reported their levels of peer victimization, and caregivers reported on their use of restriction of child food intake. Child height and weight were obtained from medical records. RESULTS: Ethnic minority adolescent females were more likely to be obese than nonethnic minority adolescents/children. Greater child body mass index (BMI)-z was associated with increased caregiver restriction (B = 0.86, p < .05) and peer victimization (B = 0.66, p < .05). When peer victimization was entered into the model of BMI-z predicting caregiver restriction of child food intake, the relationship between these 2 variables decreased from 74% to 46% and was no longer significant (B = 0.68, p = .08). However, the test of the indirect effect was not significant. CONCLUSIONS: Greater degree of overweight was associated with increased peer victimization, which in turn related to caregiver restriction of food intake. Children's social relationships may serve as an impetus for caregivers to engage in child weight control practices. Clinicians should regularly screen for weight-related peer difficulties and provide caregivers with guidance on healthy versus unhealthy weight control practices to promote overall child health. PMID- 25119489 TI - The recombinant expression systems for structure determination of eukaryotic membrane proteins. AB - Eukaryotic membrane proteins, many of which are key players in various biological processes, constitute more than half of the drug targets and represent important candidates for structural studies. In contrast to their physiological significance, only very limited number of eukaryotic membrane protein structures have been obtained due to the technical challenges in the generation of recombinant proteins. In this review, we examine the major recombinant expression systems for eukaryotic membrane proteins and compare their relative advantages and disadvantages. We also attempted to summarize the recent technical strategies in the advancement of eukaryotic membrane protein purification and crystallization. PMID- 25119497 TI - On the nature of non-covalent interactions in isomers of 2,5-dichloro-1,4 benzoquinone dimers - ground- and excited-state properties. AB - The competition between non-covalent interactions (NCIs), such as C-H???O, C H???Cl, C-Cl???O, C-Cl???Cl-C, C-O???C, C-Cl???C and C-O???pi, in the isomers of the 2,5-dichloro-1,4-benzoquinone (DCBQ) dimer were investigated by quantum chemical calculations to study the properties of the ground and excited states. All the interactions were identified through bond critical points (BCP) with an atoms in molecule (AIM) study. Isomer 1 (IH) and isomer 6 (IP) were surprisingly very stable, and the largest stabilization energies of 4.16 and 5.39 kcal mol( 1), respectively, were observed for the ground state and 5.67 and 6.07 kcal mol( 1), respectively, were observed for the excited state at the MP2/6-31++G(d,p) level of theory. The orientations of the excited-state isomers were similar to those of the ground-state except for isomer 5 (IX) and isomer 9 (IM), which disturbed the relative energy stability order. The calculated absorption spectra have shown two absorption splits for isomers 5, 7, 8 and 9 through the acute angle between the transition dipole moment of the monomers. The circular dichroism (CD) couplet of the CD spectrum and the value of optical rotation (OR) have indicated that isomers 1, 3, 5, 7, 8 and 9 have chiral characteristics. The study of the absorption and CD spectra has revealed the impact of intermolecular NCIs on chirality. PMID- 25119498 TI - MacroH2A suppresses the proliferation of the B16 melanoma cell line. AB - MacroH2A is the most frequently altered histone, which participates in cancer progression. Increasing evidence demonstrates that cancer progression could be regulated by macroH2A by affecting the cell cycle. In the present study, it was demonstrated that macroH2A suppresses melanoma cell progression and the molecular mechanisms underlying this process were examined. The interference and overexpression vectors of macroH2A were constructed and then transferred into B16 melanoma cells and, following transfection, were analyzed by quantitative polymerase chain reaction (PCR), western blot analysis and immunofluorescence assays. Apoptosis and the cell cycle stage among all the treatment groups were detected. Then, cyclin D1, cyclin D3, cyclin-dependent protein kinase (CDK) 4, CDK6 and CDK8 expression was detected in order to elucidate the effects of macroH2A on cell cycle-related genes. The results demonstrated that the overexpression of macroH2A suppressed melanoma cell progression and arrested the cells in the G2/M stage. Furthermore, macroH2A inhibits cyclin D1, cyclin D2, CDK6 and CDK8 expression in B16 melanoma cells. In conclusion, the results demonstrated that macroH2A, a critical component of chromatin, suppresses the development of melanoma (which results from a disordered cell cycle) through regulating cyclin D1, cyclin D3 and CDK6 genes. PMID- 25119499 TI - Use of linked electronic health records to assess mortality and length of stay associated with pandemic influenza A(H1N1)pdm09 at a UK teaching hospital. AB - Effective use of data linkage is becoming an increasingly important focus in the new healthcare system in England. We linked data from the results of a multiplex PCR assay for respiratory viruses for a population of 230 inpatients at a UK teaching hospital with their patient administrative system records in order to compare the mortality and length of stay of patients who tested positive for influenza A(H1N1)pdm09 with those positive for another influenza A virus. The results indicated a reduced risk of death among influenza A(H1N1)pdm09 patients compared to other influenza A strains, with an adjusted risk ratio of 0.25 (95% confidence interval 0.08-0.75, P = 0.01), while no significant differences were found between the lengths of stay in the hospital for these two groups. Further development of such methods to link hospital data in a routine fashion could provide a rapid means of gaining epidemiological insights into emerging infectious diseases. PMID- 25119500 TI - Development and cross-validation of prognostic models to assess the treatment effect of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients. AB - Better understanding of the treatment effect of cisplatin/pemetrexed chemotherapy on lung adenocarcinoma patients is needed to facilitate chemotherapy planning and patient care. In this retrospective study, we will develop prognostic models by the cross-validation method using clinical and serum factors to predict outcomes of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients. Lung adenocarcinoma patients admitted between 2008 and 2013 were enrolled. 29 serum parameters of laboratory tests and 14 clinical factors were analyzed to develop the prognostic models. First, the stepwise selection and five-fold cross validation were performed to identify candidate prognostic factors. Then a classification of all patients based on the number of metastatic sites resulted in four distinct subsets. In each subset, a prognostic model was fitted with the most accurate prognostic factors from the candidate prognostic factors. Categorical survival prediction was estimated using a log-rank test and visualized with Kaplan-Meier method. 227 lung adenocarcinoma patients were enrolled. Twenty candidate prognostic factors evaluated using the five-fold cross validation method were total protein, total bilirubin, direct bilirubin, creatine kinase, age, smoking index, neuron-specific enolase, bone metastasis, total triglyceride, albumin, gender, uric acid, CYFRA21-1, lymph node metastasis, liver metastasis, lactate dehydrogenase, CA153, peritoneal metastasis, CA125, and CA199. From these 20 candidate prognostic factors, the multivariate Cox proportional hazard model with the highest prognostic accuracy in each subset was identified by the stepwise forward selection method, which generated significant prognostic stratifications in Kaplan-Meier survival analyses (all log-rank p < 0.01). Generally, the prognostic models using five-fold cross-validation achieve a good prediction performance. The prognostic models can be administered safely to lung adenocarcinoma patients treated with first-line cisplatin/pemetrexed chemotherapy, and a comprehensive assessment of clinical and serum factors helps predict the outcomes of cisplatin/pemetrexed chemotherapy. PMID- 25119501 TI - Evaluation of docetaxel- and oxaliplatin-based adjuvant chemotherapy in postgastrectomy gastric cancer patients reveals obvious survival benefits in docetaxel-treated mixed signet ring cell carcinoma patients. AB - The purpose of this study was to determine the disease-free and overall survival (DFS and OS, respectively) in 991 postgastrectomy gastric cancer patients untreated (n = 372) or treated with either oxaliplatin-based (n = 376) or docetaxel-based (n = 243) chemotherapy and to identify prognostic factors that could help establish subgroups of patients who would benefit from such treatment. The median follow-up duration was 55.3 months (range 31.2-90.8 months). Subgroup analyses revealed that gastric adenocarcinoma (DFS 56.9 vs 53.2 months, P = 0.180, chi(2) = 1.802; OS not reached vs 70.7 months, P = 0.521, chi(2) = 0.412), but not absolute signet ring cell (SRC) carcinoma (DFS 15.1/18.0 vs 10.1 months, P = 0.171/0.259, chi(2) = 1.874/1.275; OS 21.0/26.1 vs 20.5 months, P = 0.551/0.196, chi(2) = 0.355/1.674), patients undergoing either docetaxel- or oxaliplatin-based chemotherapy had a lower risk of recurrence and increased survival in comparison to those without chemotherapy. In the mixed SRC carcinoma patients, DFS and OS of patients treated with docetaxel-based regimen had a longer survival (DFS 50.1 vs 29.9 months, P = 0.046, chi(2) = 3.987; OS not reached vs 48.6 months, P = 0.016, chi(2) = 5.854) and lower risk of recurrence and death (DFS HR 0.540, 95 % CI 0.355-0.874, P = 0.012; OS HR 0.452, 95 % CI 0.259-0.790, P = 0.005) than oxaliplatin-based chemotherapy. Cumulatively, our results indicate that adjuvant chemotherapy is beneficial and that docetaxel based regimen should be considered for patients with mixed SRC carcinoma. PMID- 25119502 TI - EBP50 inhibits the migration and invasion of human breast cancer cells via LIMK/cofilin and the PI3K/Akt/mTOR/MMP signaling pathway. AB - The scaffold protein ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50, also known as NHERF1 or NHERF) inhibits epidermal growth factor (EGF)-induced breast cancer cell proliferation after 3 days by blocking EGF receptor (EGFR) phosphorylation. The loss of EBP50 stimulates EGFR activity and induces the appearance of epithelial-to-mesenchymal transition phenotypic features in biliary cancer cells. However, the involvement of EBP50 in breast cancer migration and invasion remains unknown. We report that EBP50 inhibits the migration and invasion of breast cancer cells by inhibiting the phosphorylation of LIN-11, Isl1, and MEC-3 protein domain kinase, as well as cofilin. This phosphorylation is a critical step in cofilin recycling and actin polymerization mediating cytoskeletal rearrangement. Additionally, EGF-induced phosphorylation of Akt and mTOR was suppressed by upregulation of EBP50. Our results indicate that EBP50 is significantly involved in breast cancer invasion/metastasis via LIMK/cofilin and the PI3K/Akt/mTOR/MMP signaling pathway. PMID- 25119503 TI - Toxicity of concurrent chemoradiotherapy with cetuximab for locoregionally advanced nasopharyngeal carcinoma. AB - Overexpression of the epidermal growth factor receptor can be found in 80 % of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and is associated with shorter survival. In this work, we evaluated the feasibility of adding cetuximab to concurrent cisplatin and radiotherapy (RT) in locoregionally advanced NPC. Twenty-eight patients with locoregionally advanced NPC who received the combination therapy were retrospectively reviewed and short-term efficacy was evaluated. Grade 3-4 oral mucositis occurred in 20 (71.4 %) patients. Grade 3 radiotherapy-related dermatitis occurred in seven patients (25 %). Three patients (14.3 %) had grade 3 and one patient (3.6 %) had grade 4 cetuximab-related acneiform rashes. These grade 3-4 skin and mucosal toxic effects were manageable and reversible. At a median follow-up of 33.4 months (95 % CI 29.2-38.1 months), the 2-year progression-free survival was 89.3 % (95 % CI 76.4-98.1 %). In conclusion, concurrent administration of cetuximab, cisplatin and RT is a feasible strategy against locoregionally advanced NPC. Preliminary survival data compare favorably with historic data and further follow-up is warranted. PMID- 25119504 TI - Co-expression of EGFR and CK5/6 in primary squamous cell carcinoma of the breast. AB - Primary squamous cell carcinoma of the breast (PSCCB) is an extremely rare breast tumor lacking hormone receptors and HER2 expression. However, in comparison with triple-negative invasive ductal carcinoma (TN-IDC), little is known about the PSCCB. Twenty-nine patients with PSCCB in Sun Yat-sen University Cancer Center from 1995 to 2010 were recruited in this study, along with 681 cases of TN-IDC during the same period. The clinicopathologic features and prognosis of PSCCB compared to TN-IDC were assessed. Furthermore, biomarkers of EGFR, CK5/6, E cadherin, VEGF, TOPII, and p53 were immunostained to investigate the prognostic determinant of PSCCB. Patients with PSCCB were older than those with TN-IDC (P = 0.009) and presented with lower lymph node involvement (P = 0.015). There was no difference in overall survival (OS) between PSCCB and TN-IDC. However, the disease-free survival (DFS) of PSCCB was poorer than that of TN-IDC (P = 0.007). Multivariate analysis revealed that combined over-expression of EGFR and CK5/6 was the only independent prognostic factor for OS of PSCCB (HR 6.08, 95 % CI 1.33 27.85, P = 0.020) and associated with lymphatic metastasis (P = 0.023) and p53 expression (P = 0.013). Other predictors for poorer OS and DFS were lymphatic metastasis and stage III, which failed to show significance after multivariate analysis. Furthermore, platinum-based chemotherapy was identified to improve the OS of PSCCB with EGFR + CK5/6+ (P = 0.027). The prognosis of PSCCB is poorer than that of TN-IDC. As the only independent prognostic factor for PSCCB, combined over-expression of EGFR and CK5/6 might be a potential indicator for the use of platinum-based chemotherapy. PMID- 25119505 TI - Biomimetic Randall's plaque as an in vitro model system for studying the role of acidic biopolymers in idiopathic stone formation. AB - Randall's plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques and subsequently stones form. One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides induce a liquid phase amorphous precursor to the mineral, yielding non equilibrium crystal morphologies. Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put forth the hypothesis that the PILP system may be involved in urolithiasis. Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation to study the role that various acidic macromolecules may play. In our initial experiments presented here, the development of "biomimetic" RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. To mimic the tissue environment, MatriStem((r)) (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface and a tunica propria layer, thus providing the two types of matrix constituents found associated with mineral in the early stages of RP formation. We found that when using the PILP process to mineralize this tissue matrix, the two sides led to dramatically different mineral textures, and they bore a striking resemblance to native RP, which was not seen in the tissue mineralized via the classical crystal nucleation and growth process. The interstitium side predominantly consisted of collagen associated mineral, while the luminal side had much less mineral, which appeared to be tiny spherules embedded within the basement membrane. Although these studies are only preliminary, they support our hypothesis that kidney stones may involve non-classical crystallization pathways induced by the large variety of macromolecular species in the urinary environment. We believe that mineralization of native tissue scaffolds is useful for developing a model system of stone formation, with the ultimate goal of developing strategies to avoid RP and its detrimental consequences in stone formation, or developing therapeutic treatments to prevent or cure the disease. Supported by NIDDK grant RO1DK092311. PMID- 25119508 TI - Nitroxide-labeled pyrimidines for non-covalent spin-labeling of abasic sites in DNA and RNA duplexes. AB - Non-covalent and site-directed spin labeling gives easy access to spin-labeled nucleic acids for the study of their structure and dynamics by electron paramagnetic resonance (EPR) spectroscopy. In a search for improved spin labels for non-covalent binding to abasic sites in duplex DNA and RNA, ten pyrimidine derived spin labels were prepared in good yields and their binding was evaluated by continuous wave (CW)-EPR spectroscopy. Most of the spin labels showed lower binding affinity than the previously reported label c towards abasic sites in DNA and RNA. The most promising labels were triazole-linked spin labels and a pyrrolocytosine label. In particular, the N1-ethylamino derivative of a triazole linked uracil spin label binds fully to both DNA and RNA containing an abasic site. This is the first example of a spin label that binds fully through non covalent interactions with an abasic site in RNA. PMID- 25119507 TI - R2CHADS2 score is significantly associated with ankle-brachial index <0.9 in patients without atrial fibrillation. AB - OBJECTIVE: Previous studies demonstrated CHADS2 score and impaired renal function were both associated with ankle-brachial index (ABI) < 0.9 in patients without atrial fibrillation (AF). Hence, we hypothesized the R2CHADS2 score had a significant correlation with ABI < 0.9 and the aim of this study was to validate this association in non-AF patients. METHODS: A total of 1482 patients without AF were included. ABI was measured using an ABI-form device. Peripheral arterial occlusive disease (PAOD) was defined as ABI < 0.9 in either leg. RESULTS: Of the 1482 subjects, the prevalence of ABI < 0.9 was 5.6%. Multivariate analysis showed that increased age (odds ratio [OR], 1.049; P < 0.001), decreased estimated glomerular filtration rate (OR, 0.978; P = 0.006), and increased R2CHADS2 score (OR, 1.738; P < 0.001) were associated with ABI < 0.9. In addition, in patients with CHADS2 score ? 2, the presence of chronic kidney disease (CKD) was significantly associated with ABI < 0.9 (P ? 0.006), but in patients with CHADS2 score < 2, there was no such association (P = 0.357). CONCLUSIONS: Our study demonstrated R2CHADS2 score was positively correlated with ABI < 0.9. In addition, the presence of CKD was a risk factor of ABI < 0.9 in patients with CHADS2 score ? 2. Hence, increased R2CHADS2 score in non-AF patients and the presence of CKD in non-AF patients with CHADS2 score ? 2 were useful parameters in identifying the high risk group of PAOD. PMID- 25119509 TI - Improving the Multidisciplinary Treatment of Chronic Pain by Stimulating Body Awareness: A Cluster-randomized Trial. AB - BACKGROUND: Because of methodological flaws and a lack of theoretical foundation of body awareness (BA) in previous effect studies of interventions directed to stimulate BA, it is impossible to attribute treatment effects to this specific component of a multidisciplinary treatment. Therefore, this study evaluated short term and long-term effects of a multidisciplinary pain rehabilitation program with and without psychomotor therapy (PMT), which focused on BA (measured by the scale of body connection) as a primary target of intervention. METHODS: Ninety four patients clustered in 20 treatment groups were cluster randomized, using a biased-coin design, to multidisciplinary treatment as usual with or without PMT. Outcome variables were health-related quality of life, disability, and depression. BA, catastrophizing, and self-efficacy were measured as potential process variables. Assessments were performed at baseline, directly after treatment, and at 3, 6, and 12 month follow-ups. The data were analyzed by linear mixed-model analysis according to the intention-to-treat principle. RESULTS: Data of all 94 patients were used for analyses. After treatment, significant differences favoring PMT were found between conditions on depression (regression coefficient [RC]=-5.01; 95% confidence interval [CI], -8.81 to -1.21), BA (RC=0.23; 95% CI, 0.04 to 0.42) and catastrophizing (RC=-4.76; 95% CI, -8.03 to 1.48). These differences were no longer significant for depression at the 3-month follow-up and for catastrophizing at the 6-month follow-up. CONCLUSIONS: No clinical meaningful differences were found between treatment conditions in the primary outcome measures health-related quality of life and disability. However, this is the first long-term RCT that has shown that PMT improves BA in patients with chronic pain and shows good effect size and a significant decrease for catastrophizing. PMID- 25119506 TI - Unified theory on the pathogenesis of Randall's plaques and plugs. AB - Kidney stones develop attached to sub-epithelial plaques of calcium phosphate (CaP) crystals (termed Randall's plaque) and/or form as a result of occlusion of the openings of the Ducts of Bellini by stone-forming crystals (Randall's plugs). These plaques and plugs eventually extrude into the urinary space, acting as a nidus for crystal overgrowth and stone formation. To better understand these regulatory mechanisms and the pathophysiology of idiopathic calcium stone disease, this review provides in-depth descriptions of the morphology and potential origins of these plaques and plugs, summarizes existing animal models of renal papillary interstitial deposits, and describes factors that are believed to regulate plaque formation and calcium overgrowth. Based on evidence provided within this review and from the vascular calcification literature, we propose a "unified" theory of plaque formation-one similar to pathological biomineralization observed elsewhere in the body. Abnormal urinary conditions (hypercalciuria, hyperoxaluria, and hypocitraturia), renal stress or trauma, and perhaps even the normal aging process lead to transformation of renal epithelial cells into an osteoblastic phenotype. With this de-differentiation comes an increased production of bone-specific proteins (i.e., osteopontin), a reduction in crystallization inhibitors (such as fetuin and matrix Gla protein), and creation of matrix vesicles, which support nucleation of CaP crystals. These small deposits promote aggregation and calcification of surrounding collagen. Mineralization continues by calcification of membranous cellular degradation products and other fibers until the plaque reaches the papillary epithelium. Through the activity of matrix metalloproteinases or perhaps by brute physical force produced by the large sub-epithelial crystalline mass, the surface is breached and further stone growth occurs by organic matrix-associated nucleation of CaOx or by the transformation of the outer layer of CaP crystals into CaOx crystals. Should this theory hold true, developing an understanding of the cellular mechanisms involved in progression of a small, basic interstitial plaque to that of an expanding, penetrating plaque could assist in the development of new therapies for stone prevention. PMID- 25119510 TI - Experimental Pelvic Pain Impairs the Performance During the Active Straight Leg Raise Test and Causes Excessive Muscle Stabilization. AB - OBJECTIVES: The active straight leg raise (ASLR) test is widely used clinically to assess severity of lumbopelvic pain due to decreased stability of the sacroiliac joint (SIJ). This study aimed to bypass the influence of decreased SIJ stability on the ASLR test by investigating the effect of experimental pelvic pain and hyperalgesia on the outcome of the ASLR test. METHODS: Thirty-four healthy participants took part in this randomized crossover study. Pelvic pain was induced by injecting hypertonic saline into the long posterior sacroiliac ligament. Isotonic saline was injected on the contralateral side as control. Pain intensity was assessed on an electronic visual analogue scale. The Likert scores of difficulty performing the ASLR test and simultaneous electromyography of trunk and thigh muscles were recorded before, during, and postpain. Pressure pain thresholds were assessed bilaterally in the pelvic area and lower limb. RESULTS: Compared with the control condition and baseline, hypertonic saline injections caused (P<0.05): (1) higher visual analogue scale scores of the pain intensity; (2) reduced pressure pain thresholds at the injection site and lateral to S2; (3) increased difficulty in performing the ASLR rated on the Likert scale; and (4) bilateral increase in the electromyography activity of stabilizing trunk and thigh muscles during pain. DISCUSSION: These data demonstrate that pain and hyperalgesia in conditions unaffected by biomechanical SIJ impairments change the outcome of the ASLR test toward what is seen in clinical lumbopelvic pain. This may implicate pain-related changes in motor control strategies potentially relevant for the transition from acute into chronic pain. PMID- 25119512 TI - Effect of spinal cord stimulation on sensory characteristics: a randomized, blinded crossover study. AB - OBJECTIVES: Spinal cord stimulation (SCS) is increasingly used to treat various chronic pain conditions. One undetermined issue is to what extent SCS alters the processing of sensory information from the periphery, including those stimuli that are mediated by small-fiber populations. We aimed to investigate these possible changes using quantitative sensory testing (QST). METHODS: Fourteen patients in long-term SCS treatment for complex regional pain syndrome (n=5) or pain following peripheral nerve injury (n=9) were examined with QST. All patients answered questions about their pain and underwent QST while the SCS treatment was activated and deactivated (12 h interval between the sessions) in a randomized, double-blinded crossover setting. Both the painful side and the corresponding contralateral side were examined. RESULTS: Thermal and mechanical thresholds were similar during SCS activation and deactivation. The same result was found for intensity of pain and areas with painful symptoms even though all patients had documented long-term benefit of the treatment. DISCUSSION: The results support existing evidence suggesting that SCS does not change sensory characteristics, which is important information for both patients and clinicians. Changes in pain intensity after deactivation of SCS may be different in short-term and long-term SCS treatment. PMID- 25119511 TI - Onset of analgesia and efficacy of ibuprofen sodium in postsurgical dental pain: a randomized, placebo-controlled study versus standard ibuprofen. AB - OBJECTIVES: A novel, immediate-release tablet formulation of ibuprofen (IBU) sodium dihydrate, Advil Film Coated Tablets (IBUNa), has been developed that is absorbed faster than standard IBU tablets. The objective of the current study was to compare the efficacy and onset of analgesia of this new formulation with standard IBU tablets after a single dose. MATERIALS AND METHODS: Patients (N=316) with at least moderate baseline postsurgical dental pain were randomized to 400 mg IBUNa, Advil (IBUAdv), Motrin (IBUMot), or placebo. Primary endpoints were time-weighted sum of pain relief (PR) and pain intensity differences over 8 hours (SPRID 0-8) and time to onset of meaningful pain relief (TMPR) measured by the double-stopwatch method. RESULTS: SPRID 0-8 was significantly greater for IBUNa and the other active treatments versus placebo (P<0.001). IBUNa had a significantly earlier TMPR versus placebo, pooled IBUAdv/IBUMot, and IBUMot (P<0.001 for all), and a marginally faster TMPR (P=0.075) versus IBUAdv. Results for secondary endpoints were similar. Adverse events were comparable across treatment groups, with gastrointestinal disorders being most frequently reported. Most adverse events were mild or moderate. DISCUSSION: This novel formulation of IBUNa provided superior overall PR compared with placebo and more rapid onset of analgesic effect compared with standard IBU tablets. Rapid PR is important in the treatment of acute pain, including dental pain, and this IBUNa formulation represents a new treatment option for rapid PR. PMID- 25119513 TI - Does Change Occur for the Reasons We Think It Does? A Test of Specific Therapeutic Operations During Cognitive-Behavioral Treatment of Chronic Pain. AB - OBJECTIVE: To examine the relative validity of 2 conceptual models-Specific, General-by which therapeutic mechanisms in cognitive-behavioral therapy (CBT) for chronic pain achieve favorable outcomes. METHODS: As part of a clinical trial of enhanced versus standard CBT, people with chronic pain received treatment consisting of 3 pain coping skill modules. In secondary analyses of a subsample (n=56), we examined pretreatment to session 4 (of 10 sessions) changes in Chronic Pain Coping Inventory subscales that corresponded to receipt of one of 3 modules; namely Relaxation, Exercise, and Cognitive Coping modules. RESULTS: Findings indicated that: (1) participants receiving the Relaxation module improved more than other groups in relaxation skills, and improved substantially on other coping skills, as well; (2) participants receiving Exercise and Cognitive Coping modules showed mixed improvements and did not improve more than other groups on exercise use or cognitive coping, respectively; and (3) measures of patient therapist working alliance and patient expectations of treatment benefit at session three correlated significantly with some coping skills changes. DISCUSSION: Change with CBT may occur both by theory-specified mechanisms and general mechanisms. However, the results provide the most support for a General Mechanism model in which changes on coping skills have spreading effects on the use of other coping skills. Significant relationships between some skill changes and indexes of patient-therapist working alliance and outcome expectations suggest that nonspecific factors also play a role in treatment-related changes in the use of pain coping strategies. PMID- 25119514 TI - Living Life With My Child's Pain: The Parent Pain Acceptance Questionnaire (PPAQ). AB - OBJECTIVE: Parents' emotional, cognitive, and behavioral responses are highly influential on children's pain and functional outcomes. One important response to pediatric pain is acceptance: the degree to which an individual participates in routine daily activities in the presence of pain and is willing to let pain be a part of their life without efforts to control or avoid it. However, no tool currently exists to assess parents' own acceptance of their child's pain. The aim of this study was to validate the Parent Pain Acceptance Questionnaire (PPAQ). MATERIALS AND METHODS: The PPAQ was administered to 310 parents of youth with chronic pain in an outpatient pediatric headache program and a day hospital pain rehabilitation program. An exploratory factor analysis revealed 2 factors for the PPAQ: an 11-item Activity Engagement scale and a 4-item Acceptance of Pain related Thoughts and Feelings scale. RESULTS: The PPAQ total score and subscales demonstrated strong internal consistency. Greater parent pain acceptance was positively associated with child pain acceptance, and was negatively correlated with parent protective behaviors, parent minimizing behaviors, parent and child pain catastrophizing, and child fear of pain. Parent protective behaviors and child pain acceptance both served as mediators of the relationship between parent pain acceptance and child functional disability. CONCLUSIONS: The PPAQ is a valid measure of parent pain acceptance and may provide valuable insights into parent responses to child pain and the ways in which parent acceptance influences child outcomes. Clinical implications and suggestions for future research are discussed. PMID- 25119515 TI - The impacts of information about the risks and benefits of pork consumption on Chinese consumers' perceptions towards, and intention to eat, pork. AB - This study investigates the impacts of information on the benefits and risks of eating pork on Chinese consumers' attitudes and intentions. Data were collected in March 2013 through a consumer survey (n=909) in Beijing and Baoding City. An experiment was conducted using three types of message (positive, negative, and balanced) combined with three information sources (government, research institutes, and the pork industry). Participants ate pork almost every second day. They perceived pork as rather nutritious and relatively expensive and had neutral views about its healthiness and safety. Exposure to negative information (about risks only) resulted in a significant and negative change in consumers' perceptions of pork's nutritional value, price, healthiness and safety, while exposure to positive information (about benefits only) caused a positive change in consumers' perceptions about pork's healthiness and safety. Exposure to balanced information resulted in a significant and negative change in the perceived nutritional value of pork. Participants' intended frequency of pork consumption was significantly lower after exposure to information, irrespective of the type of information received. Exposure to risks-only information decreased consumers' intention to eat pork, while exposure to benefit-only information had a positive effect on consumers' intentions to eat pork. Exposure to balanced risk/benefit information had no effect on intended pork consumption. Of the information used, governmental materials were found to have a positive impact on consumers' perceptions of pork's safety. Implications for communication strategies with Chinese consumers about pork consumption are discussed. PMID- 25119516 TI - Complete sequence analysis of mitochondrial DNA and telomere length in aplastic anemia. AB - The present study was primarily undertaken to examine the hypothesis that mitochondrial DNA (mtDNA) mutations and telomere length may be associated with aplastic anemia (AA). Our study included a single institution analysis of 40 patients presenting with AA first diagnosed at the Affiliated Hospital of Shandong, University of Traditional Chinese Medicine between 2010 and 2013. Bone marrow and oral epithelial samples were collected from patients with AA (n=40) for mtDNA mutation and telomere length determinations. Bone marrow specimens were collected from 40 healthy volunteers as controls for the examination of telomere length. The mitochondrial genome was amplified by polymerase chain reaction (PCR), and the products were used for sequencing and analysis. We detected 146 heteroplasmic mutations in 18 genes from 40 patients with AA, including 39 silent mutations and 28 frameshift mutations. We used the gamma globin gene (HBG) as the control gene in real-time PCR to survey the relative telomere length measurements of the patients with AA and the healthy volunteers. Telomere length was expressed as the relative T/S value. We observed a negative correlation between the mtDNA non-silent mutation and the white blood cell (WBC) count, hemoglobin and platelet count. Of note, there was a positive correlation between the relative T/S value and WBC count, hemoglobin and platelet count, and a negative correlation between the non-silent mutation and the relative T/S value. We conclude that the functional impairment of the mitochondrial respiratory chain induced by mutation and telomere length shortening may play an important role in the process of hematopoietic failure in patients with AA. Additionally, mtDNA mutations and telomere length shortening influenced each other. PMID- 25119518 TI - Supplement use by UK-based British Army soldiers in training. AB - The use of supplements is widespread at all levels of civilian sport and a prevalence of 60-90 % is reported among high-performance UK athletes, including juniors. The prevalence of supplement use among UK-based British Army personnel is not known. The aim of the present study was to establish the point prevalence of supplement use in UK-based British Army soldiers under training (SuTs) and associated staff. A cross-sectional anonymous survey was carried out in 3168 British Army SuTs and soldiers, equating to 3.1 % of regular Army strength, based at eleven Phase 1, 2 and 3 UK Army training sites. Overall, 38 % of the respondents reported current use of supplements, but prevalence varied according to the course attended by the respondents. The number of different supplements used was 4.7 (sd 2.9). Supplements most commonly used were protein bars, powders and drinks (66 %), isotonic carbohydrate-electrolyte sports drinks (49 %), creatine (38 %), recovery sports drinks (35 %), multivitamins (31 %) and vitamin C (25 %). A small proportion of respondents reported the use of amphetamines and similar compounds (1.6 %), cocaine (0.8 %), anabolic androgenic steroids (1.1 %), growth hormone (2.0 %), and other anabolic agents, e.g. testosterone (4.2 %). Logistic regression modelling indicated that, for current users, younger age, being female, smoking and undergoing Officer Cadet training were associated with greater supplement use. This is the first study to investigate the prevalence of dietary and training supplement use in UK-based British military personnel. Self administration of a wide range of supplements is reported by British military personnel in training, which is at least as great as that reported by those on deployment, and has implications for Defence policy and educational needs. PMID- 25119519 TI - Cold region bioremediation of hydrocarbon contaminated soils: do we know enough? PMID- 25119521 TI - Patterns in the use of low-dose acetylsalicylic acid and other therapies following upper gastrointestinal bleeding. AB - BACKGROUND: Anticoagulants and/or antiplatelet agents such as acetylsalicylic acid (ASA) are important in prevention of cardiovascular (CV) events, but may be associated with upper gastrointestinal bleeding (UGIB). However, discontinuing these agents may leave patients at risk of CV events. OBJECTIVES: This study aimed to assess patterns of therapy after UGIB in routine clinical practice. METHODS: The Health Improvement Network UK primary care database was used to identify a cohort of patients aged 40-84 years with a UGIB event between 2000 and 2007 (n = 2,036). Patients were followed up for 1 year from the recorded UGIB. Re prescription rates for antithrombotics and drugs that can modify the risk of UGIB were estimated at 30, 90, 180, and 365 days. RESULTS: At 365 days, the re prescription rate was 43 % for ASA, 66 % for warfarin, 69 % for clopidogrel, and 49 % for dipyridamole. The re-prescription rate of gastroprotective agents at 365 days for current users of histamine H2-receptor antagonists was 36 % and that of proton pump inhibitors (PPIs) was 97 %. In patients who were prescribed ASA before UGIB (n = 572), only 24 % were prescribed a PPI in the previous year. In patients who were prescribed ASA in the year after UGIB (n = 337), 92 % were prescribed a PPI. CONCLUSIONS: Antiplatelet use fell after UGIB events. In patients who were prescribed a PPI after a UGIB event, there was increased re prescription of antiplatelet agents and antithrombotics. PMID- 25119522 TI - 5'-Guanosine monophosphate mediated biocompatible porous hydrogel of beta-FeOOH viscoelastic behavior, loading, and release capabilities of freeze-dried gel. AB - The present manuscript reports the characterization, optimization of rheological properties, and loading and release capabilities of 5'-GMP mediated beta-FeOOH hydrogel. Circular dichroism (CD) analysis indicates it to contain mainly the left-handed helix similar to that of Z-DNA. The highest viscosity (>300 cP) corresponds to the sample containing 2.5 * 10(-3) mol dm(-3) of 5'-GMP (SP2H). Field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM) studies indicate the freeze-dried (FD) SP2H to be porous in nature, which is also supported by its high Brunauer-Emmett-Teller (BET) surface area of 226 m(2)/g as compared to that of SP3H (75 m(2)/g). Selected area electron diffraction (SAED) analysis and Raman spectroscopy show it to contain beta-FeOOH phase. The FD SP2H exhibits the high swelling ratio (326%) and loading capacity for methylene blue (MB) dye. It displays a controlled and efficient release (>90%) for optimized [MB] (2.5 * 10(-4) mol dm(-3)) in 48 h. The low toxicity of as synthesized FD SP2H nanostructures against MDA-MB-231 (breast cancer cells) up to 100 MUg/mL suggests its biocompatible nature. The high porosity, surface area, % swelling, and loading and release performance of the hydrogel indicate its potential for drug delivery and other biological applications. PMID- 25119523 TI - Transition-metal-free tandem oxidative removal of benzylic methylene group by C-C and C-N bond cleavage followed by intramolecular new aryl C-N bond formation under radical conditions. AB - A novel tandem oxidative conversion of 10,11-dihydro-5H dibenzo[b,e][1,4]diazepines to phenazines has been achieved under transition metal-free, mild conditions using K2S2O8 or DDQ as the oxidizing agent. The transformation proceeds through oxidative removal of a benzylic methylene group by C-C and C-N bond cleavage followed by a new aryl C-N bond formation under radical conditions. PMID- 25119520 TI - Self-titrating anticoagulant nanocomplexes that restore homeostatic regulation of the coagulation cascade. AB - Antithrombotic therapy is a critical portion of the treatment regime for a number of life-threatening conditions, including cardiovascular disease, stroke, and cancer; yet, proper clinical management of anticoagulation remains a challenge because existing agents increase the propensity for bleeding in patients. Here, we describe the development of a bioresponsive peptide-polysaccharide nanocomplex that utilizes a negative feedback mechanism to self-titrate the release of anticoagulant in response to varying levels of coagulation activity. This nanoscale self-titrating activatable therapeutic, or nanoSTAT, consists of a cationic thrombin-cleavable peptide and heparin, an anionic polysaccharide and widely used clinical anticoagulant. Under nonthrombotic conditions, nanoSTATs circulate inactively, neither releasing anticoagulant nor significantly prolonging bleeding time. However, in response to life-threatening pulmonary embolism, nanoSTATs locally release their drug payload and prevent thrombosis. This autonomous negative feedback regulator may improve antithrombotic therapy by increasing the therapeutic window and decreasing the bleeding risk of anticoagulants. PMID- 25119524 TI - Homogeneous photochemical water oxidation by biuret-modified Fe-TAML: evidence of Fe(V)(O) intermediate. AB - Water splitting, leading to hydrogen and oxygen in a process that mimics natural photosynthesis, is extremely important for devising a sustainable solar energy conversion system. Development of earth-abundant, transition metal-based catalysts that mimic the oxygen-evolving complex of photosystem II, which is involved in oxidation of water to O2 during natural photosynthesis, represents a major challenge. Further, understanding the exact mechanism, including elucidation of the role of active metal-oxo intermediates during water oxidation (WO), is critical to the development of more efficient catalysts. Herein, we report Fe(III) complexes of biuret-modified tetra-amidomacrocyclic ligands (Fe TAML; 1a and 1b) that catalyze fast, homogeneous, photochemical WO to give O2, with moderate efficiency (maximum TON = 220, TOF = 0.76 s(-1)). Previous studies on photochemical WO using iron complexes resulted in demetalation of the iron complexes with concomitant formation of iron oxide nanoparticles (NPs) that were responsible for WO. Herein, we show for the first time that a high valent Fe(V)(O) intermediate species is photochemically generated as the active intermediate for the oxidation of water to O2. To the best of our knowledge, this represents the first example of a molecular iron complex catalyzing photochemical WO through a Fe(V)(O) intermediate. PMID- 25119527 TI - Perturbation of the charge density between two bridged Mo2 centers: the remote substituent effects. AB - A series of terephthalate-bridged dimolybdenum dimers with various formamidinate ancillary ligands, denoted as [Mo2(ArNCHNAr)3]2(MU-O2CC6H4CO2) (Ar = p-XC6H4, with X = OCH3 (1), CH3 (2), F (3), Cl (4), OCF3 (5), and CF3 (6)), has been synthesized and studied in terms of substituent effects on electron delocalization between the two dimetal sites. X-ray structural analyses show that these complexes share the same molecular scaffold with the para-substituents (X) being about 8 A away from the Mo2 center. It is found that the remote substituents have the capability to tune the electronic properties of the complexes. For the series 1 to 6, the metal-metal bond distances (d(Mo-Mo)) decrease slightly and continuously; the potential separations (DeltaE(1/2)) for the two successive one-electron oxidations decrease constantly, and the metal to ligand transition energies (lambda(max)) increase in order. More interestingly, the two types of methine protons, H(?) on the horizontal and H(?) on the vertical ligands with respect to the plane defined by the Mo-Mo bond vectors and bridging ligand, display separate resonant signals delta(?) and delta(?) in the NMR spectra. The displacements of the chemical shifts, Deltadelta(?-?) = delta(?) - delta(?), are getting smaller as the substituents vary from electron-donating to withdrawing. These results show that the peripheral groups on the [Mo2] units function to fine-tune the metal-metal interactions crossing the bridging ligand. The experimental parameters, DeltaE(1/2), lambda(max), and Deltadelta(?-?), which are linearly related with the Hammett constants (sigma(X)) of the X groups, can be used to probe the charge density on the two [Mo2] units and the electronic delocalization between them. PMID- 25119526 TI - In silico analysis of missense mutations in LPAR6 reveals abnormal phospholipid signaling pathway leading to hypotrichosis. AB - Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss disorder characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. The study, presented here, established genetic linkage in four families showing similar phenotypes to lysophosphatidic acid receptor 6 (LPAR6) gene on chromosome 13q14.11-q21.32. Subsequently, sequence analysis of the gene revealed two previously reported missense mutations including p.D63V in affected members of one and p.I188F in three other families. Molecular modeling and docking analysis was performed to investigate binding of a ligand oleoyl-L-alpha-lysophosphatidic acid (LPA) to modeled protein structures of normal and mutated (D63V, G146R, I188F, N248Y, S3T, L277P) LPAR6 receptors. The mutant receptors showed a complete shift in orientation of LPA at the binding site. In addition, hydropathy analysis revealed a significant change in the membrane spanning topology of LPAR6 helical segments. The present study further substantiated involvement of LPAR6-LPA signaling in the pathogenesis of hypotrichosis/woolly hair and provided additional insight into the molecular mechanism of hair development. PMID- 25119525 TI - The disorganized visual cortex in reelin-deficient mice is functional and allows for enhanced plasticity. AB - A hallmark of neocortical circuits is the segregation of processing streams into six distinct layers. The importance of this layered organization for cortical processing and plasticity is little understood. We investigated the structure, function and plasticity of primary visual cortex (V1) of adult mice deficient for the glycoprotein reelin and their wild-type littermates. In V1 of rl-/- mice, cells with different laminar fates are present at all cortical depths. Surprisingly, the (vertically) disorganized cortex maintains a precise retinotopic (horizontal) organization. Rl-/- mice have normal basic visual capabilities, but are compromised in more challenging perceptual tasks, such as orientation discrimination. Additionally, rl-/- animals learn and memorize a visual task as well as their wild-type littermates. Interestingly, reelin deficiency enhances visual cortical plasticity: juvenile-like ocular dominance plasticity is preserved into late adulthood. The present data offer an important insight into the capabilities of a disorganized cortical system to maintain basic functional properties. PMID- 25119528 TI - Screening of beta-secretase and acetylcholinesterase inhibitors from plant resources. AB - The therapeutic agents for dementia are limited due to the complex system underlying the mechanisms. Taking a preventive point of view, we focused on the inhibition of beta-secretase and acetylcholinesterase (AChE). In addition, plant resources including herbs and spices have been widely consumed, and further, may be consumed for a long period over a lifetime. Considering this background, we screened beta-secretase and AChE inhibitors from curry spices. Amongst them, curry leaf, black pepper, and turmeric extracts were effective to inhibit beta secretase. Furthermore, black pepper and turmeric extracts were also effective to inhibit AChE. Having these results in hand, we focused on the investigation of beta-secretase inhibitors since the inhibitor of this enzyme has not previously been well investigated. As a result, alpha- and beta-caryophyllene, beta caryophyllene oxide (from curry leaf), piperine (from black pepper), curcumin, demethoxycurcumin, and bisdemethoxycurcumin (from turmeric) were successfully identified as low molecular inhibitors. This is the first report to determine alpha- and beta-caryophyllene, beta-caryophyllene oxide, and piperine as beta secretase inhibitors. These compounds may pass through the blood brain barrier since their molecular weights are relatively low. PMID- 25119529 TI - Enhanced ultra-low-frequency interlayer shear modes in folded graphene layers. AB - Few-layer graphene has attracted tremendous attention owing to its exceptional electronic properties inherited from single-layer graphene and new features led by introducing extra freedoms such as interlayer stacking sequences or rotations. Effectively probing interlayer shear modes are critical for unravelling mechanical and electrical properties of few-layer graphene and further developing its practical potential. Unfortunately, shear modes are extremely weak and almost fully blocked by a Rayleigh rejecter in Raman measurements. This greatly hinders investigations of shear modes in few-layer graphene. Here, we demonstrate enhancing of shear modes by properly folding few-layer graphene. As a direct benefit of the strong signal, enhancement mechanism, vibrational symmetry, anharmonicity and electron-phonon coupling of the shear modes are uncovered through studies of Raman mapping, polarization- and temperature-dependent Raman spectroscopy. This work complements Raman studies of graphene layers, and paves an efficient way to exploit low-frequency shear modes of few-layer graphene and other two-dimensional layered materials. PMID- 25119530 TI - Contrasting behavior of heterochromatic and euchromatic chromosome portions and pericentric genome separation in pre-bouquet spermatocytes of hybrid mice. AB - The spatial distribution of parental genomes has attracted much interest because intranuclear chromosome distribution can modulate the transcriptome of cells and influence the efficacy of meiotic homologue pairing. Pairing of parental chromosomes is imperative to sexual reproduction as it translates into homologue segregation and genome haploidization to counteract the genome doubling at fertilization. Differential FISH tagging of parental pericentromeric genome portions and specific painting of euchromatic chromosome arms in Mus musculus (MMU) * Mus spretus (MSP) hybrid spermatogenesis disclosed a phase of homotypic non-homologous pericentromere clustering that led to parental pericentric genome separation from the pre-leptoteneup to zygotene stages. Preferential clustering of MMU pericentromeres correlated with particular enrichment of epigenetic marks (H3K9me3), HP1-gamma and structural maintenance of chromosomes SMC6 complex proteins at the MMU major satellite DNA repeats. In contrast to the separation of heterochromatic pericentric genome portions, the euchromatic arms of homeologous chromosomes showed considerable presynaptic pairing already during leptotene stage of all mice investigated. Pericentric genome separation was eventually disbanded by telomere clustering that concentrated both parental pericentric genome portions in a limited nuclear sector of the bouquet nucleus. Our data disclose the differential behavior of pericentromeric heterochromatin and the euchromatic portions of the parental genomes during homologue search. Homotypic pericentromere clustering early in prophase I may contribute to the exclusion of large repetitive DNA domains from homology search, while the telomere bouquet congregates and registers spatially separated portions of the genome to fuel synapsis initiation and high levels of homologue pairing, thus contributing to the fidelity of meiosis and reproduction. PMID- 25119534 TI - Seasonal variation and source apportionment of organic tracers in PM10 in Chengdu, China. AB - Organic compound tracers including n-alkanes, triterpane, sterane, polycyclic aromatic hydrocarbons (PAHs) and dicarboxylic acids of airborne particulate matter (PM10) were characterized for samples collected at five sites from July 2010 to March 2011 using GC/MS. Spatial and temporal variations of these organic tracers in PM10 were studied, and their sources were then identified respectively. Average daily concentrations of PM10 varied in different seasons with the trend of PM10 in winter (0.133 mg/m(3)) > autumn (0.120 mg/m(3)) > spring (0.103 mg/m(3)) > summer (0.098 mg/m(3)). Daily concentrations of n alkanes (C11-C36) ranged from 12.11 to 163.58 ng/m(3) with a mean of 61.99 ng/m(3). The C max and CPI index of n-alkanes indicated that vehicle emissions were the major source in winter, while the contributions of high plant wax emissions became significant in other seasons. It was discovered that the main sources of triterpenoid and steranes were gasoline and diesel engine emissions. Concentrations of ?15PAHs in PM10 also varied (12.25-58.56 ng/m(3)) in different seasons, and chrysene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(ghi) perylene and fluoranthene were the dominant components. In the four seasons, the concentration of ?15PAHs was relatively higher at the northern site because of traffic congestion. The main source of airborne PAHs was traffic emissions and coal combustion. Average daily concentrations of dicarboxylic acids (C4-C10) in PM10 ranged from 12.11 to 163.58 ng/m(3), of which azeleic acid was the major compound (0.49-52.04 ng/m(3), average 14.93 ng/m(3)), followed by succinic acid (0.56-19.08 ng/m(3), average 6.84 ng/m(3)). The ratio of C6/C9 showed that the major source in winter was biological, while the contributions of emissions from anthropogenic activities were much higher in summer. PMID- 25119532 TI - Comorbidities among the HIV-infected patients aged 40 years or older in Taiwan. AB - BACKGROUND: With the widespread use of combination antiretroviral therapy (cART), life expectancy of HIV-infected patients has significantly prolonged. An increasing number of HIV-infected patients are aging and concurrent use of medications are not uncommon for management of metabolic complications and cardiovascular diseases related to aging and prolonged exposure to cART. METHODS: We reviewed medical records of all HIV-infected patients aged 40 years or older who had been followed at a university hospital for HIV care in Taiwan between January and December 2013. A standardized case record form was used to collect information on demographics and clinical characteristics, comorbidity, cART, and concurrent medications. RESULTS: During the study period, 610 patients aged 40 to 49 years (mean, 44.1) and 310 aged 50 years or older (mean, 58.8) sought HIV care at this hospital. Compared with patients aged 40 to 49 years, those aged 50 years or older were significantly more likely to be female (15.9% vs 3.8%); to have received cART (97.7% vs 94.8%) and a lower plasma HIV RNA load (1.6 vs 1.7 log10 copies/ml); and to have diabetes mellitus (18.4% vs 4.6%), hypertension (31.0% vs 10.8%), hyperlipidemia (29.4% vs 11.6%), coronary artery disease (6.8% vs 0.5%), and an estimated glomerular filtration rate <60 ml/min/1.73 m2 (11.5% vs 2.7%); and were significantly less likely to have syphilis. Other than HIV infection, patients aged 50 years or older were more likely to have been receiving two or more concurrent medications than those aged 40 to 49 years (22.9% vs 6.4%). CONCLUSIONS: Our findings show a significant proportion of the HIV-infected patients aged 50 years or older have multiple comorbidities that may increase the risk for cardiovascular and renal complications. Issues of poly-pharmacy among the HIV-infected patients who are aging should be addressed to ensure adherence and minimize drug-drug interactions. PMID- 25119535 TI - Chronic kidney disease of unknown aetiology and ground-water ionicity: study based on Sri Lanka. AB - High incidence of chronic kidney disease of unknown aetiology (CKDU) in Sri Lanka is shown to correlate with the presence of irrigation works and rivers that bring in 'nonpoint source' fertilizer runoff from intensely agricultural regions. We review previous attempts to link CKDU with As, Cd and other standard toxins. Those studies (e.g. the WHO-sponsored study), while providing a wealth of data, are inconclusive in regard to aetiology. Here, we present new proposals based on increased ionicity of drinking water due to fertilizer runoff into the river system, redox processes in the soil and features of 'tank'-cascades and aquifers. The consequent chronic exposure to high ionicity in drinking water is proposed to debilitate the kidney via a Hofmeister-type (i.e. protein-denaturing) mechanism. PMID- 25119537 TI - [Femoral nailing using a helical nail shape (LFN((r)))]. AB - OBJECTIVE: Antegrade femoral nailing through a greater trochanteric entry portal avoids damage to the proximal external rotators and to the ramus profundus of the medial femoral circumflex artery, furthermore eases insertion in adipose subjects. However a helical nail shape is necessary for this pathway because bending in two perpendicular planes has to be passed by the nail. INDICATIONS: All femoral shaft fractures suitable for antegrade nailing (type 32-A/B/C). Additional femoral neck fractures (type 31-B) by using proximal Recon interlocking screws. CONTRAINDICATIONS: The common contraindications for femoral nailing. In certain subtrochanteric fractures (Type 32-A/B) the proximal femoral nail may be favorable. SURGICAL TECHNIQUE: General or spinal anesthesia. Supine position with flexion/abduction of the contralateral leg in order to facilitate fluoroscopy of the proximal femur in a true lateral view. Closed reduction of length and axis. Measurement of length and diameter of the nail using a radiolucent ruler. Dorsolateral approach to the greater trochanter. Insertion of the guide wire 10 mm lateral to the trochanteric tip (anteroposterior view) and in the middle third of the trochanter (lateral view). Reaming of the insertion point using a flexible reamer. If reaming of the entire medullary canal is desired, this should be done using a long intramedullary guide wire in combination with a long flexible reamer. Insertion of the nail starts in an anterior position and ends in a lateral position of the insertion instrument, so a 90 degrees external rotation of the nail occurs during insertion. Proximal interlocking is performed using the guide of the insertion instrument. Check interfragmentary rotation. Distal interlocking using a radiolucent drill device. POSTOPERATIVE MANAGEMENT: Depends on the fracture shape: stable interfragmentary support may allow early full weight bearing. Otherwise, reduced weight bearing is recommended for at least 6 weeks. RESULTS: In a prospective mulicentric study, 227 helical femoral nails were used for antegrade femoral nailing. Follow-up after 12 month was available in 74 %. Surgeons' rating for ease of identifying entry site was excellent or good in 89 %. Functional and radiological results after 12 months do not prove significant benefits over conventional antegrade femoral nails. PMID- 25119538 TI - Lysophosphatidic acid induces anxiety-like behavior via its receptors in mice. AB - Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator with diverse biological properties. We previously found altered expression of the LPA-related genes in rodents after treatment with sertraline, which is widely used to treat anxiety disorders and depression. However, little is known about the behavioral effects of LPA. In the present study, we investigated the behavioral effects of intracerebroventricular injection of LPA in adult mice. LPA did not significantly affect spontaneous locomotor activity, suggesting that LPA does not induce hyperactivity, ataxia, or sedation. We next investigated the emotional effects of LPA via the hole-board test. LPA significantly increased the number of head-dips in a dose- and time-related manner. A significant induction of head-dip counts occurred 15 and 30 min after LPA administration. To clarify the involvement of LPA receptors, we examined the effect of the non-selective LPA1-4 receptor antagonist, 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (BrP-LPA) co administered with LPA. BrP-LPA dose-dependently inhibited LPA-induced head-dip counts. We next investigated anxiety-like behavior via the elevated plus-maze test. LPA significantly reduced the percentage of time spent in the open arms and BrP-LPA dose-dependently inhibited this anxiety-like behavior. In conclusion, LPA induced anxiety-like behavior in mice via LPA receptors. Our results suggest that LPA signaling plays an important role in regulating anxiety in mice. PMID- 25119536 TI - The Hepatocyte Growth Factor (HGF)/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms? AB - Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML), and myeloproliferative neoplasms (MPNs). The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs). PMID- 25119540 TI - A prospective, randomized, controlled trial of the postoperative analgesic effects of spraying 0.25 % levobupivacaine after bilateral axillo-breast approach robotic thyroidectomy. AB - BACKGROUND: Robotic thyroidectomy (RoT) is frequently performed due to its excellent cosmesis and recovery features. However, postoperative pain in the operating field after RoT remains a concern due to extensive tissue dissection and tension during the operation. The aim of this study was to evaluate the anterior chest pain and the effect of levobupivacaine spraying on postoperative pain control after bilateral axillo-breast approach (BABA) RoT. METHODS: We randomized 55 adult patients scheduled for BABA RoT into the control group (group C, n = 27) or the levobupivacaine group (group L, n = 28). At the end of surgery, patients in groups C and L were sprayed with the same volume (30 ml) of normal saline and 0.25 % levobupivacaine, respectively, on the flap dissection area. Pain scores, the consumption of patient-controlled analgesia (PCA), and other adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. RESULTS: Patients in group L showed lower pain scores than those of group C at 1 h (50 [0 100] vs. 80 [20-100]; p = 0.004), 6 h (30 [0-90] vs. 70 [30-90]; p < 0.001), 24 h (30 [0-80] vs. 50 [10-80]; p = 0.016) and 48 h (10 [0-80] vs. 30 [10-80]; p < 0.001) postoperatively. PCA consumption of group L was less than that of group C at 6, 24, and 48 h after surgery. There were no significant differences in postoperative nausea-vomiting, headache, or dizziness. Local anesthetic-related adverse effects were not reported. CONCLUSION: Levobupivacaine spray on the operative field at the end of BABA RoT reduced postoperative pain and PCA consumption without adverse events. PMID- 25119539 TI - Common mechanisms in neurodegeneration and neuroinflammation: a BrainNet Europe gene expression microarray study. AB - Neurodegenerative diseases of the central nervous system are characterized by pathogenetic cellular and molecular changes in specific areas of the brain that lead to the dysfunction and/or loss of explicit neuronal populations. Despite exhibiting different clinical profiles and selective neuronal loss, common features such as abnormal protein deposition, dysfunctional cellular transport, mitochondrial deficits, glutamate excitotoxicity, iron accumulation and inflammation are observed in many neurodegenerative disorders, suggesting converging pathways of neurodegeneration. We have generated comparative genome wide gene expression data, using the Illumina HumanRef 8 Beadchip, for Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, Parkinson's disease, and schizophrenia using an extensive cohort (n = 113) of well-characterized post-mortem brain tissues. The analysis of whole-genome expression patterns across these major disorders offers an outstanding opportunity not only to look into exclusive disease-specific changes, but more importantly to look for potential common molecular pathogenic mechanisms. Surprisingly, no dysregulated gene that passed our selection criteria was found in common across all six diseases. However, 61 dysregulated genes were shared when comparing five and four diseases. The few genes highlighted by our direct gene comparison analysis hint toward common neuronal homeostatic, survival and synaptic plasticity pathways. In addition, we report changes to several inflammation-related genes in all diseases. This work is supportive of a general role of the innate immune system in the pathogenesis and/or response to neurodegeneration. PMID- 25119542 TI - Magnetic lower esophageal sphincter augmentation device removal. AB - Implantation of a magnetic lower esophageal sphincter augmentation device is now an alternative to fundoplication in the surgical management of gastroesophageal reflux disease (GERD). Although successful management of GERD has been reported following placement of the device, there are instances when device removal is needed. The details of the technique for laparoscopic magnetic lower esophageal sphincter device removal are presented to assist surgeons should device removal become necessary. PMID- 25119541 TI - Systematic review of the clinical and cost effectiveness of cholecystectomy versus observation/conservative management for uncomplicated symptomatic gallstones or cholecystitis. AB - BACKGROUND: Gallstone disease is a common gastrointestinal disorder in industrialised countries. Although symptoms can be severe, some people can be symptom free for many years after the original attack. Surgery is the current treatment of choice, but evidence suggests that observation is also feasible and safe. We reviewed the evidence on cholecystectomy versus observation for uncomplicated symptomatic gallstones and conducted a cost-effectiveness analysis. METHODS: We searched six electronic databases (last search April 2014). We included randomised controlled trials (RCTs) or non-randomised comparative studies where adults received either cholecystectomy or observation/conservative management for the first episode of symptomatic gallstone disease (biliary pain or cholecystitis) being considered for surgery in secondary care. Meta-analysis was used to combine results. A de novo Markov model was developed to assess the cost effectiveness of the interventions. RESULTS: Two RCTs (201 participants) were included. Eighty-eight percent of people randomised to surgery and 45 % of people randomised to observation underwent cholecystectomy during the 14-year follow-up period. Participants randomised to observation were significantly more likely to experience gallstone-related complications (RR = 6.69, 95 % CI = 1.57 28.51, p = 0.01), in particular acute cholecystitis (RR = 9.55, 95 % CI = 1.25 73.27, p = 0.03), and less likely to undergo surgery (RR = 0.50, 95 % CI = 0.34 0.73, p = 0.0004) or experience surgery-related complications (RR = 0.36, 95 % CI = 0.16-0.81, p = 0.01) than those randomised to surgery. Fifty-five percent of people randomised to observation did not require surgery, and 12 % of people randomised to cholecystectomy did not undergo surgery. On average, surgery costs L1,236 more per patient than conservative management, but was more effective. CONCLUSIONS: Cholecystectomy is the preferred treatment for symptomatic gallstones. However, approximately half the observation group did not require surgery or suffer complications indicating that it may be a valid alternative to surgery. A multicentre trial is needed to establish the effects, safety and cost effectiveness of observation/conservative management relative to cholecystectomy. PMID- 25119544 TI - Expression profiling of sucrose metabolizing genes in Saccharum, Sorghum and their hybrids. AB - Sucrose phosphate synthase (SPS; EC 2.4.1.14), sucrose synthase (SuSy; EC 2.4.1.13) and soluble acid invertase (SAI; EC 3.2.1.26) are key enzymes that regulate sucrose fluxes in sink tissues for sucrose accumulation in sugarcane and sorghum. In this study, the expression profiling of sucrose-related genes, i.e. SPS, SuSy and SAI in two sets of hybrids viz., one from a Sorghum * Saccharum cross and the other from a Saccharum * Sorghum cross, high- and low-sucrose varieties, sweet and grain sorghum lines was carried out using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) at monthly intervals. The results indicated differential expression of the three genes in high- and low sucrose forms. Expression of SPS and SuSy genes was high in high-sucrose varieties, Saccharum * Sorghum hybrids and sweet sorghum and lower in low-sucrose varieties, Sorghum * Saccharum hybrids and grain sorghum. SAI showed a lower expression in high-sucrose varieties, Saccharum * Sorghum hybrids and sweet sorghum and higher expression in low-sucrose varieties, Sorghum * Saccharum hybrids and the grain sorghum. This study describes the positive association of SPS and SuSy and negative association of SAI on sucrose accumulation. This is the first report of differential expression profiling of SPS, SuSy and SAI in intergeneric hybrids involving sugarcane and sorghum, which opens the possibility for production of novel hybrids with improved sucrose content and with early maturity. PMID- 25119543 TI - Immunoadjuvant activity of the nanoparticles' surface modified with mannan. AB - Mannan (MN) is the natural ligand for mannose receptors, which are widely expressed on dendritic cells (DCs). The purpose of this study was to assess the effect of formulation parameters on the immunogenicity of MN-decorated poly (D, L lactide-co-glycolide) (PLGA) nanoparticles (NPs) in terms of their ability to stimulate DC phenotypic as well as functional maturation. For this purpose, NPs were formulated from either ester-terminated or COOH-terminated PLGA. Incorporation of MN in NPs was achieved through encapsulation, physical adsorption or chemical conjugation. Murine bone marrow derived DCs (BMDCs) were treated with various NP formulations and assessed for their ability to up regulate DC cell surface markers, secrete immunostimulatory cytokines and to activate allogenic T cell responses. DCs treated with COOH-terminated PLGA-NPs containing chemically conjugated MN (MN-Cov-COOH) have shown superior performance in improving DC biological functions, compared to the rest of the formulations tested. This may be attributed to the higher level of MN incorporation in the former formulation. Incorporation of MN in PLGA NPs through chemical conjugation can lead to enhanced DC maturation and stimulatory function. This strategy may be used to develop more effective PLGA-based vaccine formulations. PMID- 25119545 TI - Anti-bactericidal properties of stingray Dasyatis pastinaca groups V, IIA, and IB phospholipases A2: a comparative study. AB - Group IIA secreted phospholipase A2 (group IIA sPLA2) is known to display potent Gram-positive bactericidal activity in vitro and in vivo. We have analyzed the bactericidal activity of the full set of native stingray and dromedary groups V, IIA, and IB sPLA2s on several Gram-positive and Gram-negative strains. The rank order potency among both marine and mammal sPLA2s against Gram-positive bacteria is group IIA > V > IB, whereas Gram-negative bacteria exhibited a much higher resistance. There is a synergic action of the sPLA2 with lysozyme when added to the bacteria culture prior to sPLA2.The bactericidal efficiency of groups V and IIA sPLA2s was shown to be dependent upon the presence of calcium ions and to a less extent Mg(2+) ions and then a correlation could be made to its hydrolytic activity of membrane phospholipids. Importantly, we showed that stingray and dromedary groups V, IIA, and IB sPLA2s present no cytotoxicity after their incubation with MDA-MB-231cells. stingray groups V and IIA sPLA2s, like mammal ones, may be considered as future therapeutic agents against bacterial infections. PMID- 25119546 TI - Development of optimal medium content for bioelements accumulation in Bacopa monnieri (L.) in vitro culture. AB - Bacopa monnieri is one of the most interesting plants from the Ayurveda system. The aims of present research were, basing on in vitro shoot culture of B. monnieri, to determine content and to evaluate the influence of physiologically important metabolites on the selected bioelements accumulation in biomass. The most significant increase in biomass production was observed in the culture medium enriched with 0.5 mg/L of anthranilic acid. In this medium also, the highest accumulation of Mg was noted. The highest concentration of iron was determined in B. monnieri in vitro culture enriched with 0.25 g/L of serine. The addition of L-tryptophan, magnesium sulfate, and zinc hydroaspartate caused only a small increase in the accumulation of copper in B. monnieri. Increase in Zn accumulation was obtained in biomass from in vitro culture of B. monnieri with the addition of magnesium sulfate and zinc hydroaspartate. In the case of Na, the maximum level of this element was in biomass from medium enriched with zinc hydroaspartate. Twofold increase in K concentration was obtained in biomass from cultures on medium with addition of serine and magnesium sulfate. The concentrations of Ca in biomass of all studied media were at the similar level. PMID- 25119547 TI - Genome shuffling enhances lipase production of thermophilic Geobacillus sp. AB - Thermostable lipases are potential enzymes for biocatalytic application. In this study, the lipase production of Geobacillus sp. CF03 (WT) was improved by genome shuffling. After two rounds of genome shuffling, one fusant strain (FB1) achieved increase lipase activity from the populations generated by ultraviolet irradiation and ethyl methylsulfonate (EMS) mutagenesis. The growth rate and lipase production of FB1 increased highest by 150 and 238 %, respectively, in comparison to the wild type. The fusant enzyme had a significant change in substrate specificity but still prefers the long-chain length substrates. It had an optimum activity at 60 degrees C, pH at 7.0-8.0, with p-nitrophenyl palmitate (C16) as a substrate and retained about 50 % of their activity after 15 min at 70 degrees C, pH 8.0. Furthermore, the fusant lipase showed the preference of sesame oil, waste palm oil, and canola oil. Therefore, the genome shuffling strategy has been successful to strain improvement and selecting strain with multiple desirable characteristics. PMID- 25119548 TI - Lipid production of microalga Ankistrodesmus falcatus increased by nutrient and light starvation in a two-stage cultivation process. AB - The aim of this work was to study the stimulation of lipid production on the microalga Ankistrodesmus falcatus by varying cultivation conditions during the stationary phase. The effect of three factors (presence and absence of nitrogen, phosphorus, and light) has been tested once the cultures reached the stationary phase with the aim to increase the value of the biomass for further applications. Lipid content, elemental composition, Nile red fluorescence evolution, and calorific value of microalgal biomass were studied as well as biomass growth. Biomass presented a lipid content of 36.54 % at the end of the first stage, while at the end of the second stage, the experiments with the absence of phosphorus increased their lipid content until 45.94 and 44.55 %, the first with nitrogen and light presence and the second with absence of all factors. The combination of phosphorus absence and nitrogen and light presence achieved the highest lipid productivity (20.27 mg/L/day). The two-stage strategy to culture microalgae is a feasible option to increase the economic or energetic value of biomass. PMID- 25119549 TI - The application of the Biolog EcoPlate approach in ecotoxicological evaluation of dairy sewage sludge. AB - An increasing amount of sewage sludge requires reasonable management, whereas its storage might be environmentally hazardous. Due to the organic matter and nutrient presence in sediments, it may be used as organic fertilizer. However, beyond the valuable contests, sewage sludge can also contain toxic or dangerous ingredients like heavy metals. Therefore, there is a need to develop methods for rapid assessment of sediment ecotoxicity that will determine its possible applicability in agriculture. The Biolog(r) EcoPlate enables the metabolic profile diversity evaluation of microbial populations in environmental samples, which reflects the state of their activity. It is regarded as a modern technology that by means of biological properties allows quick characterization of the ecological status of environmental samples, such as sewage sludge. PMID- 25119550 TI - Continuous esterification of free fatty acids in crude biodiesel by an integrated process of supercritical methanol and sodium methoxide catalyst. AB - An integrated process of supercritical methanol (SCM) and sodium methoxide catalyst was developed to produce fatty acid methyl esters (FAMEs) via continuous esterification from crude biodiesel. The crude biodiesel with high free fatty acid (FFA) content must be refined to reduce the acid value (AV) for meeting the quality standards. The process parameters were studied by Box-Behnken design (BBD) of response surface methodology (RSM). The experimental results revealed that the AV of crude biodiesel decreased from 18.66 to 0.55 mg KOH g(-1) at the reaction conditions of 350 degrees C, 0.5 % amount of sodium methoxide catalyst, and 10 MPa. Temperature shows the most significant effect on the esterification, followed by pressure and amount of sodium methoxide catalyst. This integrated process proved to be a potential route to refine the crude biodiesel because of its continuity, high efficiency, and less energy consumption with relatively moderate reaction conditions compared with conventional methods. PMID- 25119551 TI - Effect of phytase application during high gravity (HG) maize mashes preparation on the availability of starch and yield of the ethanol fermentation process. AB - Phytic acid present in raw materials used in distilling industry can form complexes with starch and divalent cations and thus limit their biological availability. The influence of the enzymatic hydrolysis of phytate complexes on starch availability during the alcoholic fermentation process using high gravity (HG) maize mashes was analyzed. Indicators of the alcoholic fermentation as well as the fermentation activity of Saccharomyces cerevisiae D-2 strain were statistically evaluated. Phytate hydrolysis improved the course of the alcoholic fermentation of HG maize mashes. The final ethanol concentration in the media supplemented with phytase applied either before or after the starch hydrolysis increased by 1.0 and 0.6 % v/v, respectively, as compared to the control experiments. This increase was correlated with an elevated fermentation yield that was higher by 5.5 and 2.0 L EtOH/100 kg of starch, respectively. Phytate hydrolysis resulted also in a statistically significant increase in the initial concentration of fermenting sugars by 14.9 mg/mL of mash, on average, which was a consequence of a better availability of starch for enzymatic hydrolysis. The application of phytase increased the attenuation of HG media fermentation thus improving the economical aspect of the ethanol fermentation process. PMID- 25119552 TI - Effect of electroporation on bioconversion of isoflavones and probiotic properties of parents and subsequent passages of Bifidobacterium longum. AB - This study aimed to evaluate the effects of electroporation on growth, bioconversion of isoflavones, and probiotic properties of parent organisms and subsequent passages of Bifidobacterium longum FTDC 8643. Electroporation with the strength of electric field at 7.5 kV cm(-1) for 3.5 ms was applied on B. longum FTDC 8643. The viability of B. longum FTDC 8643 increased significantly upon treatment with electroporation. Such treatment also enhanced the intracellular and extracellular beta-glucosidase activity, leading to enhanced production of bioactive isoflavone aglycones in mannitol-soymilk (P < 0.05). In addition, these treated cells also exhibited better tolerance toward acidic (pH 2 and pH 3) and intestinal bile salt condition compared to the control (P < 0.05). The electroporated cell also possessed better adhesion ability and antimicrobial activity (P < 0.05). However, all these positive effects were only prevalent in the parent cells and were not observed in their subsequent passages of electroporated cells. Our results suggested that electroporation could enhance the bioactive and probiotic potentials of parent cells of B. longum FTDC 8643 and could be used in the production of probiotic foods with enhanced bioactivity. PMID- 25119553 TI - Targeting improvements in patient safety at a large academic center: an institutional handoff curriculum for graduate medical education. AB - PROBLEM: Handoffs are an integral component of patient care, and the number of handoffs has increased as a result of duty hours restrictions for resident physicians. A structured handoff curriculum improves accuracy and has been shown to decrease medical errors. A standardized approach across all specialties is lacking in the published literature. The authors discuss the development and implementation of an institution-wide handoff curriculum for incoming first-year residents. APPROACH: An Innovation in Graduate Medical Education committee, including faculty from multiple specialties, identified an educational deficiency in handoffs and selected this as the target for the educational innovation. Meetings were held to develop and implement an extensive handoff curriculum for incoming first-year residents. The designed curriculum included large- and small group sessions, and a specialty-specific observed simulated handoff experience. The authors analyzed participants' pre- and postsurveys using descriptive statistics. OUTCOMES: One hundred and twenty-four participants attended the formalized handoff training day. Following training, residents recognized that dedicated time for verbal exchange, templates for accessing and recording information, interactive handoffs giving priority to ill patients, and highlighting action items were most important for effective handoff. NEXT STEPS: Both undergraduate and graduate medical education curricula need to develop formalized training and methods to assess competencies in handoffs. Training incoming residents is a logical starting place, but programs should be systematically disseminated across all specialties, from residents to faculty, in order to be effectively integrated into the culture of an institution. PMID- 25119554 TI - Time well spent: the association between time and effort allocation and intent to leave among clinical faculty. AB - PURPOSE: To explore the relationship between clinical faculty members' time/effort in four mission areas, their assessment of the distribution of that time/effort, and their intent to leave the institution and academic medicine. METHOD: Faculty from 14 U.S. medical schools participated in the 2011-2012 Faculty Forward Engagement Survey. The authors conducted multivariate logistic regression analyses to evaluate relationships between clinical faculty members' self-reported time/effort in each mission area, assessment of time/effort, and intent to leave the institution and academic medicine. RESULTS: Of the 13,722 clinical faculty surveyed, 8,349 (60.8%) responded. Respondents reported an average of 54.5% time/effort in patient care. The authors found no relationship between time/effort in patient care and intent to leave one's institution. Respondents who described spending "far too much/too much" time in patient care were more likely to report intent to leave their institution (odds ratio 2.12, P<.001). Those who assessed their time/effort in all mission areas as "about right" were less likely to report intent to leave their institution (64/1,135; 5.6%) than those who reported "far too little/too little" or "far too much/too much" time/effort in one or more mission areas (535/3,671; 14.6%; P<.001). CONCLUSIONS: Although the authors found no relationship between reported time/effort in patient care and intent to leave, the perception of "far too much/too much" time/effort spent in that mission area was correlated with intent to leave the institution. Efforts to align time/effort spent in each mission area with faculty expectations may improve retention. PMID- 25119555 TI - The Quality Improvement Knowledge Application Tool Revised (QIKAT-R). AB - PURPOSE: Quality improvement (QI) has been part of medical education for over a decade. Assessment of QI learning remains challenging. The Quality Improvement Knowledge Application Tool (QIKAT), developed a decade ago, is widely used despite its subjective nature and inconsistent reliability. From 2009 to 2012, the authors developed and assessed the validation of a revised QIKAT, the "QIKAT R." METHOD: Phase 1: Using an iterative, consensus-building process, a national group of QI educators developed a scoring rubric with defined language and elements. Phase 2: Five scorers pilot tested the QIKAT-R to assess validity and inter- and intrarater reliability using responses to four scenarios, each with three different levels of response quality: "excellent," "fair," and "poor." Phase 3: Eighteen scorers from three countries used the QIKAT-R to assess the same sets of student responses. RESULTS: Phase 1: The QI educators developed a nine-point scale that uses dichotomous answers (yes/no) for each of three QIKAT-R subsections: Aim, Measure, and Change. Phase 2: The QIKAT-R showed strong discrimination between "poor" and "excellent" responses, and the intra- and interrater reliability were strong. Phase 3: The discriminative validity of the instrument remained strong between excellent and poor responses. The intraclass correlation was 0.66 for the total nine-point scale. CONCLUSIONS: The QIKAT-R is a user-friendly instrument that maintains the content and construct validity of the original QIKAT but provides greatly improved interrater reliability. The clarity within the key subsections aligns the assessment closely with QI knowledge application for students and residents. PMID- 25119556 TI - Gelatinases and extracellular matrix metalloproteinase inducer are associated with cyclosporin-A-induced attenuation of periodontal degradation in rats. AB - BACKGROUND: The present study aims to examine the inhibitory effect of cyclosporin-A (CsA) on periodontal breakdown and to further explore the correlations of CsA-induced attenuation of periodontal bone loss with the expressions of gelatinases (i.e., matrix metalloproteinase [MMP]-2 and MMP-9) and extracellular matrix metalloproteinase inducer (EMMPRIN). METHODS: Forty Sprague Dawley rats were randomly divided into four groups: 1) control; 2) CsA; 3) ligature (Lig); and 4) ligature plus CsA (Lig + CsA). The CsA group received 10 mg ? Kg(-1) ? d(-1) CsA for 8 days. The Lig group received silk ligature on selected molars. The Lig + CsA group received silk ligature and CsA treatment. The inhibitory effects of CsA on the ligature-induced periodontal breakdown was examined with microcomputed tomography (micro-CT) and histometric analyses to analyze the amount of attachment loss, crestal bone loss, connective tissue attachment, and the surface area with inflammatory cell infiltration. The effects of CsA on ligature-induced expressions of gelatinases and EMMPRIN in gingival tissues were examined with Western blotting and zymography, respectively. RESULTS: By micro-CT and histology, the Lig + CsA group had significantly more periodontal breakdown than the control and CsA groups but less periodontal breakdown than the Lig group. Consistent results were found for the expressions of gelatinases and EMMPRIN among the groups demonstrating that the Lig + CsA group had significantly less gingival protein expression of gelatinases and EMMPRIN than the Lig group. CONCLUSIONS: CsA inhibited the expressions of gelatinase MMPs and EMMPRIN and partially prevented the periodontal breakdown in ligature-induced experimental periodontitis. The CsA-induced attenuation of periodontal bone loss was strongly correlated positively with the expressions of MMP-2, MMP-9, and EMMPRIN in gingiva. PMID- 25119557 TI - Resistance to cigarette smoke is increased in periodontal ligament cells by attachment to collagen and fibronectin. AB - BACKGROUND: The toxic effects of cigarette smoke often presents in smokers as increased incidence and severity of periodontal disease. These patients demonstrate symptomatic inflammation, increased probing depth, and tooth loss likely attributable to the direct effects of cigarette smoke on periodontal ligament (PDL) fibroblasts. The goal of this in vitro study is to investigate the direct effects of smoking on PDL fibroblasts, focusing on cell-extracellular matrix (ECM) interactions and cell survival. METHODS: PDL cells were plated for various times on tissue culture plastic, PDL-derived ECMs, collagen Type I, or fibronectin. Cells were exposed to various concentrations of cigarette smoke extract (CSE) at different times during the cell attachment process. Subsequently, cell survival was quantified using calcein-acetoxymethyl ester compound and a fluorescent plate reader. RESULTS: After exposure to CSE, PDL cell survival increased with increased cell attachment time to plastic. These observations were independent of soluble factors present in PDL cell-conditioned media. PDL-derived ECMs and collagen Type I-pretreated plates promoted increased cell survival after 1 day of cell attachment. Fibronectin-pretreated plates demonstrated increased cell survival after 3 days of cell attachment. CONCLUSIONS: Cell-ECM interactions increase survival of PDL cells exposed to CSE. It is suggested that the increased survival is attributable to PDL cells altering their ECM, potentially by depositing collagen and fibronectin. This may imply that cells embedded in an ECM would be more resistant to the toxic effects of cigarette smoke, leading to increased cell death near the exposed edges of a wound. PMID- 25119558 TI - Association of CCL5 and CCR5 gene polymorphisms with periodontitis in Taiwanese. AB - BACKGROUND: It has been suggested that genetic factors may predispose individuals to periodontal diseases. The present case-control study aims to test whether the 403 single nucleotide polymorphism of chemokine ligand 5 (CCL5-403) and the 32-bp deletion of CCR5 (CCR5Delta32) polymorphisms are associated with susceptibility to chronic and aggressive periodontitis. METHODS: Taiwanese participants (N = 213) were grouped into control group (CG), generalized aggressive periodontitis (GAgP), or chronic periodontitis (CP) groups. DNA samples were obtained from peripheral blood. CCL5-403, evaluated by polymerase chain reaction-restriction fragment length polymorphism, and CCR5Delta32, evaluated by polymerase chain reaction, were compared among the three groups. RESULTS: There was a significant association between type of periodontitis and having allele A or G in the CCL5 403 polymorphism. GAgP patients were 3.7 times more likely than CP patients and 2.0 times more likely than CG patients to have allele A, instead of allele G, in CCL5-403. GAgP patients were 3.1 times more likely than CG patients to have AG versus GG genotype. GAgP patients were also 5.0 and 19.8 times more likely than CP patients to have AG and AA genotypes, respectively, compared to GG. For the CCR5Delta32 polymorphism, no association was found between the type of periodontitis and having different genotype or allele distributions among GAgP, CP, or CG patients. CONCLUSION: The single nucleotide polymorphism of CCL5-403 G substitution by A may play a role in AgP; however, the CCR5Delta32 polymorphism may not. PMID- 25119559 TI - Factors affecting utilization of dental services during pregnancy. AB - BACKGROUND: The aim of this study is to identify and evaluate factors affecting utilization of dental services during pregnancy. METHODS: Participants in this cross-sectional study were mothers visiting a community health center for their infants'/toddlers' immunization. Data were collected through a questionnaire about demographics, oral health knowledge, attitude, and practices, as well as barriers to dental visits during pregnancy. Mean (SD) and frequencies were used for data description. Different factors were analyzed as predictors for utilization of dental services using multiple logistic regression analysis. RESULTS: In total, 423 mothers completed the study. Mean (SD) age at delivery was 29.5 (5.3) years. Almost all participants brushed their teeth at least once daily with toothpaste. During pregnancy, 19.2% of mothers reported difficulties with brushing, and 25% had dental/periodontal problems. Half of the participants had a dental visit during pregnancy; 93% were for dental checkups, 80.5% received preventive care, and 28.8% received dental/periodontal treatments. Canadian-born women were 48% more likely to visit the dentist during pregnancy compared with non-Canadian counterparts (P = 0.048). Level of education, dental insurance, and household income were also positively associated with usage (P <0.001). Mothers with more knowledge about possible connections between oral health and pregnancy and those who visited the dentist every 6 months had better odds of visiting the dentist during pregnancy (P <0.001). CONCLUSION: Three major factors predicting the utilization of dental services during pregnancy were: 1) perceived need, 2) habit of regular dental visits, and 3) access to dental services. PMID- 25119560 TI - Periodontal disease as a risk indicator for poor physical fitness: a cross sectional observational study. AB - BACKGROUND: Physical inactivity has been associated with poor oral health. The aim of this study is to assess whether periodontal disease is a risk indicator for poor physical fitness. METHODS: This cross-sectional study included 111 males who performed a physical fitness test (PFT) composed of four exercises: 1) push ups conducted by pushing the body up and lowering it down using the arms; 2) pull ups with the body suspended by the arms gripped on a bar; 3) sit-ups in which the upper and lower vertebrae are lifted from the floor; and 4) running for 12 minutes. A PFT score (range of 1 to 300) was determined for each participant, with higher scores indicating better physical fitness. One periodontist assessed attachment loss (AL) and probing depth (PD). Physical fitness was dichotomized according to whether the highest PFT score was "achieved" or "not achieved." Multivariable logistic models were fitted adjusting for age, overweight (body mass index of 25 to 29.9 kg/m(2)), and frequency of daily exercise. RESULTS: The mean age of the sample was 34.8 +/- 10.3 years. Overweight individuals demonstrated significantly lower PFT scores (276.9 +/- 24.1 points) than normal weight individuals (289.3 +/- 16.8 points). Individuals presenting at least one tooth with AL >= 4 mm had significantly lower PFT scores (277.8 +/- 23.6 points) compared with those without this status (285.9 +/- 20.2 points). A 1-mm increment in PD or AL significantly decreased the chance of reaching the highest PFT score by 69% or 75%, respectively. CONCLUSION: Periodontal disease may be considered a risk indicator for poor physical fitness in males. PMID- 25119561 TI - Effects of scaling and root planing on clinical response and serum levels of adipocytokines in patients with obesity and chronic periodontitis. AB - BACKGROUND: Despite several investigations suggesting that obesity is a risk indicator for periodontitis, little is known about the effect of obesity on periodontal treatment response. The aim of this study is to evaluate the effects of scaling and root planing (SRP) on clinical parameters and circulating levels of leptin and adiponectin in patients with obesity with chronic periodontitis (CP). METHODS: Twenty-four patients with obesity and CP and 24 patients without obesity with CP were submitted to SRP. Clinical parameters were assessed at baseline and 3 and 6 months after therapy. Serum levels of leptin and adiponectin were evaluated at all time points, using enzyme-linked immunosorbent assay. RESULTS: SRP improved the clinical parameters of both groups at 3 and 6 months (P < 0.05). Nonetheless, the patients without obesity presented a lower mean probing depth (PD) at 6 months after therapy and a greater reduction in PD from baseline to 6 months in the full-mouth analysis (primary outcome variable) and in initially deep sites (P < 0.05). Leptin serum levels were higher in patients with obesity than in patients without obesity at all time points (P < 0.05). No changes in the serum levels of leptin and adiponectin were observed in groups with and without obesity after therapy (P > 0.05). CONCLUSIONS: Patients with obesity and CP presented lower reductions in PD than patients without obesity with CP at 6 months after SRP. Furthermore, the treatment did not affect the circulating levels of leptin and adiponectin in any group. PMID- 25119562 TI - The future of stem cell therapy in hernia and abdominal wall repair. AB - INTRODUCTION: Stem cell therapies have been proposed in preclinical trials as new treatment options in abdominal wall repair. MATERIALS AND METHODS: This work lists sources of feasible cell lines and the current status of literature and provides a cautious outlook into future developments. Special attention was paid to translational issues and practicabilty in a complex field. CONCLUSION: Cell based therapies will play a role in the clinical setting in the future. Regulatory and ethical issues need to be addressed as well as the proof of cost effectiveness. PMID- 25119563 TI - Long-term outcome after randomizing prolene hernia system, mesh plug repair and Lichtenstein for inguinal hernia repair. AB - PURPOSE: To assess long-term superiority in terms of chronic pain between prolene hernia system (PHS), mesh plug repair (MPR) and Lichtenstein (L) technique for inguinal hernia repair. METHODS: Eight years after randomizing three commonly used techniques for primary inguinal hernia repair, the outcome was evaluated with a questionnaire measuring pain on verbal descriptor and visual analogue scales, including limitations on daily life activities, sensory disturbances and recurrences. From previous results patients characteristics, operative details and short- and mid-term pain outcome were extracted. RESULTS: 270 out of 308 eligible patients (88%) completed the follow-up after median 7.6 years (range 6.9 9.2) after the inguinal hernia operation. No significant differences between the repair techniques were found for pain, sensory disturbances or recurrences. Overall, the hernia recurrence rate was 6.3%. In total 63 patients (23%) reported long-term pain of which one-fourth graded this moderate to severe. Pain was experienced at least weekly by 26 patients (10%) and limiting daily activities for 36 patients (13%). With regard to the previously reported pain at 3 and 15 months follow-up, 106 patients (39%) experience no pain at all. For 101 patients (37%), initial pain disappeared. 41 patients (15%) suffered persisting pain at all three measure moments. 22 patients (8%) reported pain at 8 years follow-up after an initial pain-free period. CONCLUSIONS: Long-term outcome after randomizing PHS, MPR and L showed no clinically relevant differences in chronic pain and its consequences. Although chronic pain is diminishing over time it remains a serious complication and has sometimes an onset long after the inguinal repair. PMID- 25119566 TI - Impact of supplementary feeding on reproductive success of white storks. AB - European white stork (Ciconia ciconia) populations have been object to several conservation measures such as reintroduction programs, habitat improvement or supplementary feeding in the last decades. Although recent white stork censuses revealed an upward trend of most of the western populations, evaluations of the relative importance of certain conservation measures are still scarce or even lacking. In our study we analyzed the effect of supplementary feeding on the reproductive success of white storks in conjunction with other factors such as weather or nest site characteristics. We present data of 569 breeding events at 80 different nest sites located in variable distances to an artificial feeding site at Affenberg Salem (south-western Germany) collected from 1990-2012. A multilevel Poisson regression revealed that in our study population (1) reproductive success was negatively affected by monthly precipitation in April, May and June, (2) pairs breeding on power poles had a lower reproductive success than pairs breeding on platforms or trees and (3) reproductive success was significantly higher in pairs breeding in close distance to the feeding site. The number of fledglings per nest decreased by 8% per kilometer distance to the feeding site. Our data suggest that supplementary feeding increases fledgling populations which may be a tool to attenuate population losses caused by factors such as habitat deterioration or unfavorable conditions in wintering habitats. PMID- 25119564 TI - Foodborne cereulide causes beta-cell dysfunction and apoptosis. AB - AIMS/HYPOTHESIS: To study the effects of cereulide, a food toxin often found at low concentrations in take-away meals, on beta-cell survival and function. METHODS: Cell death was quantified by Hoechst/Propidium Iodide in mouse (MIN6) and rat (INS-1E) beta-cell lines, whole mouse islets and control cell lines (HepG2 and COS-1). Beta-cell function was studied by glucose-stimulated insulin secretion (GSIS). Mechanisms of toxicity were evaluated in MIN6 cells by mRNA profiling, electron microscopy and mitochondrial function tests. RESULTS: 24 h exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E and pancreatic islets apoptotic, whereas cell death did not increase in the control cell lines. In MIN6 cells and murine islets, GSIS capacity was lost following 24 h exposure to 0.5 ng/ml cereulide (P<0.05). Cereulide exposure induced markers of mitochondrial stress including Puma (p53 up-regulated modulator of apoptosis, P<0.05) and general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding protein homologous protein). Mitochondria appeared swollen upon transmission electron microscopy, basal respiration rate was reduced by 52% (P<0.05) and reactive oxygen species increased by more than twofold (P<0.05) following 24 h exposure to 0.25 and 0.50 ng/ml cereulide, respectively. CONCLUSIONS/INTERPRETATION: Cereulide causes apoptotic beta-cell death at low concentrations and impairs beta-cell function at even lower concentrations, with mitochondrial dysfunction underlying these defects. Thus, exposure to cereulide even at concentrations too low to cause systemic effects appears deleterious to the beta-cell. PMID- 25119565 TI - Reduced functional reserve in patients with age-related white matter changes: a preliminary FMRI study of working memory. AB - Subcortical age-related white matter changes (ARWMC) are a frequent finding in healthy elderly people suggested to cause secondary tissue changes and possibly affecting cognitive processes. We aimed to determine the influence of the extent of ARWMC load on attention and working memory processes in healthy elderly individuals. Fourteen healthy elderly subjects (MMSE >26; age 55-80 years) performed three fMRI tasks with increasing difficulty assessing alertness, attention (0-back), and working memory (2-back). We compared activation patterns in those with only minimal ARWMC (Fazekas 0-1) to those with moderate to severe ARWMC (Fazekas 2-3). During the fMRI experiments, the study population showed activation in brain areas typically involved in attention and working memory with a recruitment of cortical areas with increasing task difficulty. Subjects with higher lesion load showed a higher activation at all task levels with only sparse increase of signal with increasing complexity. In the lower lesion load group, rising task difficulty lead to a significant and widely distributed increase of activation. Although the number of patients included in the study is small, these findings suggest that even clinically silent ARWMC may affect cognitive processing and lead to compensatory activation during cognitive tasks. This can be interpreted as a reduction of functional reserve and may pose a risk for cognitive decline in these patients. PMID- 25119567 TI - Hydroclimate variations in central and monsoonal Asia over the past 700 years. AB - Hydroclimate variations since 1300 in central and monsoonal Asia and their interplay on interannual and interdecadal timescales are investigated using the tree-ring based Palmer Drought Severity Index (PDSI) reconstructions. Both the interannual and interdecadal variations in both regions are closely to the Pacific Decadal Oscillation (PDO). On interannual timescale, the most robust correlations are observed between PDO and hydroclimate in central Asia. Interannual hydroclimate variations in central Asia are more significant during the warm periods with high solar irradiance, which is likely due to the enhanced variability of the eastern tropical Pacific Ocean, the high-frequency component of PDO, during the warm periods. We observe that the periods with significant interdecadal hydroclimate changes in central Asia often correspond to periods without significant interdecadal variability in monsoonal Asia, particularly before the 19th century. The PDO-hydroclimate relationships appear to be bridged by the atmospheric circulation between central North Pacific Ocean and Tibetan Plateau, a key area of PDO. While, in some periods the atmospheric circulation between central North Pacific Ocean and monsoonal Asia may lead to significant interdecadal hydroclimate variations in monsoonal Asia. PMID- 25119569 TI - [Germ cell and embryonal tumors]. AB - Germ cell tumors, which constitute approximately 3-5% of tumors of the central nervous system (CNS), can be subdivided into germinomas, embryonal carcinomas, yolk sac tumors, choriocarcinomas, teratomas and mixed germ cell tumors. The diagnosis of intracranial germ cell tumor is based on the clinical symptoms, detection of tumor markers, such as alpha fetoprotein (AFP) and the beta subunit of human chorionic gonadotropin (beta-hCG) in blood and cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) of the brain and spinal cord, CSF cytology and histology. The diagnosis of a secreting germ cell tumor, i.e. a non germinoma, can be made by the determination of AFP and hCG as tumor markers. Germinomas are radiosensitive but are equally as sensitive to chemotherapy. Teratomas of the CNS are mostly diagnosed in newborns and infants. The most decisive role in the treatment of teratomas is played by as complete a resection as possible. Chemotherapy and irradiation play a subordinate role.Embryonal tumors, which constitute approximately 15-20% of CNS tumors, include medulloblastomas, primitive neuroectodermal tumors (PNET) of the CNS and the atypical teratoid rhabdoid tumor of the CNS. Medulloblastoma is the most common malignant brain tumor in childhood and adolescence. The incidence peak is the fifth year of life with a male predisposition in a ratio of 1.5:1. Medulloblastomas constitute 12-25% of all pediatric CNS tumors and 30-40% of pediatric tumors of the posterior cranial fossa. At the time of diagnosis evidence of dissemination in the CSF cavity is found in approximately 40% of patients. The extreme cell density makes medulloblastomas hyperdense in computed tomography (CT) and can therefore be differentiated from hypodense astrocytomas. The PNETs are histologically related to medulloblastomas, pineoblastomas, atypical teratoid rhabdoid tumors and peripheral neuroblastomas. They are relatively rare in children constituting less than 5% of supratentorial neoplasms. Patients are mostly clinically conspicuous due to macrocephalus and signs of brain pressure and/or seizures. In native CT the solid components of PNETs show a hyperdensity compared to the surrounding brain parenchyma probably due to the high cell density. Cysts and calcification are often detectable. The survival rate of children with CNS tumors has continuously increased in recent years. When corresponding clinical symptoms appear, such as headache, nausea or vomiting when fasting, all of which are evidence of increased intracranial pressure, MRI should be carried out as quickly as possible. Children should be treated in centers with departments of pediatric oncology and hematology and within the framework of studies. PMID- 25119568 TI - Host density and competency determine the effects of host diversity on trematode parasite infection. AB - Variation in host species composition can dramatically alter parasite transmission in natural communities. Whether diverse host communities dilute or amplify parasite transmission is thought to depend critically on species traits, particularly on how hosts affect each other's densities, and their relative competency as hosts. Here we studied a community of potential hosts and/or decoys (i.e. non-competent hosts) for two trematode parasite species, Echinostoma trivolvis and Ribeiroia ondatrae, which commonly infect wildlife across North America. We manipulated the density of a focal host (green frog tadpoles, Rana clamitans), in concert with manipulating the diversity of alternative species, to simulate communities where alternative species either (1) replace the focal host species so that the total number of individuals remains constant (substitution) or (2) add to total host density (addition). For E. trivolvis, we found that total parasite transmission remained roughly equal (or perhaps decreased slightly) when alternative species replaced focal host individuals, but parasite transmission was higher when alternative species were added to a community without replacing focal host individuals. Given the alternative species were roughly equal in competency, these results are consistent with current theory. Remarkably, both total tadpole and per-capita tadpole infection intensity by E. trivolvis increased with increasing intraspecific host density. For R. ondatrae, alternative species did not function as effective decoys or hosts for parasite infective stages, and the diversity and density treatments did not produce clear changes in parasite transmission, although high tank to tank variation in R. ondatrae infection could have obscured patterns. PMID- 25119570 TI - [Soft tissue tumors : Imaging strategy for local primary diagnostics - manifestation, pearls and pitfalls in MRI]. AB - Only approximately 1% of soft tissue tumors are malignant. Potentially malignant lesions can be recognized by ultrasound and submitted for magnetic resonance imaging (MRI). Radiography can supply valuable additional information. The MRI examination is the imaging reference standard for soft tissue tumors and also serves as local staging modality. Lesions which are indeterminate in MRI, or in which therapy is dependent on histology results, should be biopsied. Referral to a reference center is recommended. The multitude of soft tissue tumor entities are classified according to the World Health Organization (WHO) system (latest version 2013). Some tumors show characteristic locations and MRI morphology. Sarcoma staging by imaging is influenced by the size and site in comparison to the surface fascia. International standards must be adhered to: decisive for the patient is in particular the care by an experienced interdisciplinary tumor team. PMID- 25119571 TI - A preliminary pilot randomized crossover study of uzara (Xysmalobium undulatum) versus ibuprofen in the treatment of primary dysmenorrhea. AB - OBJECTIVE: Preliminary evaluation of efficacy and safety of uzara use in treatment of moderate and severe primary dysmenorrhea in comparison to ibuprofen. MATERIALS AND METHODS: This randomized, comparative two way cross-over study comprised 60 single female students at Faculty of Medicine, Ain Shams University, Egypt, aged 19-28 years with moderate (n = 46) or severe (n = 14) primary dysmenorrhea. Participants were randomized to take either uzara (80 mg/8 hours for two doses, then 40 mg/8 hours) then ibuprofen (400 mg/6 hours) in two subsequent cycles or vice versa. The pain intensity, using VAS, was recorded immediately before taking the medication (0 hour) and after 4, 12, 24, 48-60, 96 120 hours. Main outcome measures included effectiveness of pain relief defined as drop of VAS to 3 or less, patient's global evaluation of the drug, absence from school, the use of a rescue medication, and, in those who continued the treatment, the pain intensity difference (PID) at different points after start of medication and its sum (SPID). RESULTS: Uzara was comparably effective to ibuprofen (78.3% vs. 86.7% of cycles; respectively), with comparable rates of effectiveness on global evaluation (being around 50% for either drug), and rates of school absences (11.7% vs. 13.3%; respectively). The need for rescue medication was different (18.3% and 10%; respectively), albeit with no statistical significance. The means of PID at different time points and SPID were comparable, with significantly lower average mean of VAS scores compared to that felt with no medication (1.6 vs. 6.8, p<0.001). Side effects were less with uzara than ibuprofen (0% vs. 8.3%, p<0.05). CONCLUSIONS: Uzara might be as effective as ibuprofen in management of primary dysmenorrhea but with less side effects. These findings need to be confirmed by a properly designed trial with a larger sample size. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25618258. PMID- 25119574 TI - Adjunctive treatments in pediatric acute respiratory distress syndrome. AB - Acute respiratory distress syndrome (ARDS) is a devastating process that involves pulmonary inflammation, alveolar damage and hypoxemic respiratory failure. Although advances in management approaches over the past two decades have resulted in significantly improved outcomes, death from pediatric ARDS may still occur in up to 35% of patients. While invasive mechanical ventilation is an essential component of ARDS management, various adjuncts have been utilized as treatment for these patients. However, evidence-based data in infants and children in this area are lacking. In this article, the authors review the available evidence supporting (or not supporting) the use of non-ventilatory adjunctive strategies in the management of pediatric ARDS, including prone positioning, pulmonary vasodilators, beta-agonists, steroids and surfactant. PMID- 25119573 TI - Dysfunction of bone marrow vascular niche in acute graft-versus-host disease after MHC-haploidentical bone marrow transplantation. AB - Acute graft-versus-host disease (aGvHD) is the most common complication of allogeneic hematopoietic stem cell transplantation (HSCT), which is often accompanied by impaired hematopoietic reconstitution. Sinusoidal endothelial cells (SECs) constitute bone marrow (BM) vascular niche that plays an important role in supporting self-renewal capacity and maintaining the stability of HSC pool. Here we provide evidences that vascular niche is a target of aGvHD in a major histocompatibility complex (MHC)-haploidentical matched murine HSCT model. The results demonstrated that hematopoietic cells derived from GvHD mice had the capacity to reconstitute hematopoiesis in healthy recipient mice. However, hematopoietic cells from healthy donor mice failed to reconstitute hematopoiesis in GvHD recipient mice, indicating that the BM niche was impaired by aGvHD in this model. We further demonstrated that SECs were markedly reduced in the BM of aGvHD mice. High level of Fas and caspase-3 expression and high rate of apoptosis were identified in SECs, indicating that SECs were destroyed by aGvHD in this murine HSCT model. Furthermore, high Fas ligand expression on engrafted donor CD4(+), but not CD8(+) T cells, and high level MHC-II but not MHC-I expression on SECs, suggested that SECs apoptosis was mediated by CD4(+) donor T cells through the Fas/FasL pathway. PMID- 25119572 TI - Tumour cells expressing single VEGF isoforms display distinct growth, survival and migration characteristics. AB - Vascular endothelial growth factor-A (VEGF) is produced by most cancer cells as multiple isoforms, which display distinct biological activities. VEGF plays an undisputed role in tumour growth, vascularisation and metastasis; nevertheless the functions of individual isoforms in these processes remain poorly understood. We investigated the effects of three main murine isoforms (VEGF188, 164 and 120) on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that express them individually under endogenous promoter control. Fibrosarcomas expressing only VEGF188 (fs188) or wild type controls (fswt) were typically mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164 and VEGF120-producing cells (fs164 and fs120 respectively) were less typically mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted rounded/amoeboid and a mix of rounded and elongated morphologies respectively. Consistent with their mesenchymal characteristics, fs188 cells migrated significantly faster than fs164 or fs120 cells on 2D surfaces while contractility inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression correlated with faster proliferation rates and lower levels of spontaneous apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences in proliferation rates and apoptosis could be explained by defective signalling downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All cells expressed tyrosine kinase VEGF receptors, but these were not active/activatable suggesting that inherent differences between the cell lines are governed by endogenous VEGF isoform expression through complex interactions that are independent of tyrosine kinase receptor activation. VEGF isoforms are emerging as potential biomarkers for anti-VEGF therapies. Our results reveal novel roles of individual isoforms associated with cancer growth and metastasis and highlight the importance of understanding their diverse actions. PMID- 25119576 TI - [(Gastro-)intestinal tract (reflections to issue 4/2014 - editorial)]. PMID- 25119575 TI - [Nerve-preserving low anterior rectum resection]. AB - AIM: The Performance of an oncological low anterior rectum resection with preservation of the sympathic and parasympathic nerves is illustrated. INDICATION: The total mesorectal excision (TME) by Robert Heald et al. is the gold standard for rectal cancer operations which has lowered drastically the local recurrence rate. As the survival data improve, the new focus is the postoperative quality of life with preserving of the bladder and sexual function. METHOD: We demonstrate an anterior rectal cancer operation with preserving of the sympathetic and parasympathetic nerves step by step. CONCLUSION: The critical parts of preserving the nerves with the N. hypogastricus superior and inferior as well as the neurovascular bundle "erigent pillar" are demonstrated. PMID- 25119577 TI - [Barrett's neoplasia: where is the problem?]. AB - The Barrett mucosa is characterised by metaplastic transformation in the distal oesophagus from squamous epithelium into columnar-lined cells and shows an increased risk for progression into adenocarcinoma. Up to date an international definition of Barrett's oesophagus is still lacking and it is also difficult to separate low-grade dysplasia/intraepithelial neoplasia from high-grade dysplasia/intraepithelial neoplasia. The present review describes the criteria for the histological diagnosis, discusses the possibilities of endoscopic diagnosis and highlights the biomarkers of the Barrett mucosa. PMID- 25119578 TI - [Helicobacter pylori: short overview on selected data from the history and their value for clinical medicine, in particular, surgery - what does the (general/abdominal) surgeon need to know]. AB - The discovery of Helicobacter pylori (H. pylori) represents one of the most notable events in the field of experimental and clinical medicine with great impact to daily practice even to surgery. It has led to a paradigm shift in the treatment of peptic ulcer disease. For the time period of almost one century, several scientists had described spiral-shaped bacteria in the stomach of animals and humans. However, it lasted till the early 1980s when Robin Warren and Barry Marshall successfully cultured H. pylori and recognised its causal relationship to chronic gastritis and peptic ulcer disease. Since then, our knowledge about H. pylori and related diseases has been continuously growing. Today, the bacterium is known to be mainly responsible for the development of chronic gastritis, peptic ulcer disease, MALT lymphoma and is considered as the main risk factor for the development of gastric cancer - all this led to a switch in the basic aetiopathogenetic considerations. In particular, eradication of H. pylori helped to i) develop an aetiology-based therapeutic and preventive approach to the diseases listed above according and adapted to findings, stage and manifestation, and ii) define a new role of surgery in the treatment concept. In addition, more and more evidence is being gathered for a possible association between the bacterium and several extragastric diseases. PMID- 25119580 TI - The placebo effect, sleep difficulty, and side effects: a balanced placebo model. AB - Medical treatment is usually accompanied by a warning about potential side effects. While constituting an important component of informed consent, these warnings may themselves contribute to side effects via the placebo effect. We tested this possibility using a 2 * 2 between-subjects design. Under the guise of a trial of a new hypnotic, 91 undergraduates experiencing difficulty sleeping were allocated to receive a warning about a target side effect (either increase or decrease in appetite, counterbalanced) or no warning and then to receive placebo treatment or no treatment for one week. Placebo treatment led to significantly better sleep on almost all self-reported outcomes, suggesting a placebo effect for reported sleep difficulty. Actigraphy recordings were unaffected by treatment. There was a clear effect of the warning in that placebo treated participants who were warned about side effects were much more likely to report the target side effect than those not warned about side effects. Implications for clinical practice are discussed. PMID- 25119582 TI - Non-invasive whole-body plethysmograph for assessment and prediction of radiation induced lung injury using simultaneously acquired nitric oxide and lung volume measurements. AB - Radiation-induced lung injury (RILI) is a prevalent side effect in patients who undergo thoracic irradiation as part of their cancer treatment. Preclinical studies play a major role in understanding disease onset under controlled experimental conditions. The aim of this work is to develop a single-chambered optimized, non-invasive, whole-body plethysmograph prototype for unrestrained small animal lung volume measurements for preclinical RILI studies. The system is also designed to simultaneously obtain nitric oxide (NO) measurements of the expired breath. The device prototype was tested using computer simulations, phantom studies and in vivo measurements in experimental animal models of RILI. The system was found to improve resemblance to true breathing signal characteristics as measured by improved skewness (21.83%) and kurtosis (51.94%) in addition to increased overall signal sensitivity (3.61%) of the acquired breath signal, when compared to matching control data. NO concentration data was combined with breath measurements in order to predict early RILI onset. The system was evaluated using serial weekly measurements in hemi-thorax irradiated rats (n = 8) yielding a classification performance of 50.0%, 62.5%, 87.5% using lung volume only, NO only, and combined measurements of both, respectively. Our results indicate that improved performance could be achieved when measurements of lung volume are combined with those of NO. This would provide the overall plethysmography system with the ability to provide useful diagnostic and prognostic information for preclinical and, potentially, clinical thoracic dose escalation studies. PMID- 25119581 TI - Therapeutic strategies for cancer treatment related peripheral neuropathies. AB - OPINION STATEMENT: Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated with multiple chemotherapeutic agents. CIPN may have a detrimental impact on patients' quality of life and functional ability, as well as result in chemotherapy dose reductions. Although symptoms of CIPN can improve with treatment completion, symptoms may persist. Currently, the treatment options for CIPN are quite limited. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, has the most evidence supporting its use in the treatment of CIPN. Other agents with potential benefit for the treatment of established CIPN include gabapentinoids, venlafaxine, tricyclic antidepressants, and a topical gel consisting of the combination of amitriptyline, ketamine, and baclofen; none of these, however, has been proven to be helpful and ongoing/future studies may well show that they are not beneficial. The use of these agents is often based on their efficacy in the treatment of non-CIPN neuropathic pain, but this does not necessarily mean that they will be helpful for CIPN-related symptoms. Other nonpharmacologic interventions including acupuncture and Scrambler therapy are supported by positive preliminary data; however, further larger, placebo controlled trial data are needed to confirm or refute their effectiveness. PMID- 25119583 TI - Blockade of epidermal growth factor receptor/mammalian target of rapamycin pathway by Icariside II results in reduced cell proliferation of osteosarcoma cells. AB - Icariside II is considered one of the most important natural flavonoids with multiple bioactivities from traditional Chinese medicine Yin Yanghuo (YYH) or Horny Goat Weed (Epimedium koreanum Nakai). Previous studies show that Icariside II exhibits potent cytotoxicity against a broad spectrum of human cancer cells through various signaling transduction pathways. However, there are few reports about the effect of Icariside II on osteosarcoma cell. In this study, we found that Icariside II decreased cell proliferation in human osteosarcoma MG-63 cells and human osteosarcoma Saos-2 cells. In addition, Icariside II inactivated EGFR/mTOR signaling pathway, including EGFR, PI3K/AKT/PRAS40, Raf/MEK/ERK as well as mTOR. Furthermore, Icariside II inhibited epidermal growth factor (EGF) induced activation of EGFR/mTOR signaling pathway. Pretreatment of EGF partially reversed cell viability decreased by Icariside II. Importantly, Icariside II inhibited the proliferation of transplantable tumors and EGFR/mTOR signaling pathway in sarcoma-180 bearing mice. In summary, these results indicate that Icariside II inhibits the proliferation of osteosarcoma cells in vitro and in vivo via EGFR/mTOR signaling pathway. PMID- 25119585 TI - Antiretroviral therapy adherence measurement in non-clinical settings in South India. AB - Optimal adherence to antiretroviral therapy (ART) is key to viral suppression, but may be impeded by psychosocial consequences of HIV-infection such as stigma and depression. Measures of adherence in India have been examined in clinic populations, but little is known about the performance of these measures outside clinical settings. We conducted a cross-sectional study of 151 Tamil-speaking people living with HIV/AIDS (PLHA) in India recruited through HIV support networks and compared single item measures from the Adult AIDS Clinical Trial Group (AACTG) scale, a visual analog scale (VAS), and a question on timing of last missed dose. Depression was measured using the Major Depression Inventory (MDI) and HIV-related stigma was measured using an adaptation of the Berger Stigma Scale. Mean age was 35.6 years (SD +/- 5.9); 55.6% were male; mean MDI score was 11.9 (SD +/- 9.1); and mean stigma score was 67.3 (SD +/- 12.0). Self reported perfect adherence (no missed doses) was 93.3% using the AACTG item, 87.1% using last missed dose, and 83.8% using the VAS. The measures had moderate agreement with each other (kappa 0.45-0.57). Depression was associated with lower adherence irrespective of adherence measure used, and remained significantly associated in multivariable analyses adjusting for age and marital status. Stigma was not associated with adherence irrespective of the measure used. The VAS captured the greatest number of potentially non-adherent individuals and may be useful for identifying PLHA in need of adherence support. Given the consistent and strong association between poorer adherence and depression, programs that jointly address adherence and mental health for PLHA in India may be more effective than programs targeting only one. PMID- 25119584 TI - A cautionary tale for autologous vascular tissue engineering: impact of human demographics on the ability of adipose-derived mesenchymal stem cells to recruit and differentiate into smooth muscle cells. AB - Autologous tissue-engineered blood vessels (TEBVs) generated using adult stem cells have shown promising results, but many preclinical evaluations do not test the efficacy of stem cells from patient populations likely to need therapy (i.e., elderly and diabetic humans). Two critical functions of these cells will be (i) secreting factors that induce the migration of host cells into the graft and (ii) differentiating into functional vascular cells themselves. The purpose of this study was to analyze whether adipose-derived mesenchymal stem cells (AD-MSCs) sourced from diabetic and elderly patients have a reduced ability to promote human smooth muscle cell (SMC) migration and differentiation potential toward SMCs, two important processes in stem cell-based tissue engineering of vascular grafts. SMC monolayers were disrupted in vitro by a scratch wound and were induced to close the wound by exposure to media conditioned by AD-MSCs from healthy, elderly, and diabetic patients. Media conditioned by AD-MSCs from healthy patients promoted the migration of SMCs and did so in a dose-dependent manner; heating the media to 56 degrees C eliminated the media's potency. AD-MSCs from diabetic and elderly patients had a decreased ability to differentiate into SMCs under angiotensin II stimulation; however, only AD-MSCs from elderly donors were unable to promote SMC migration. Gender and body-mass index of the patients showed no effect on either critical function of AD-MSCs. In conclusion, AD-MSCs from elderly patients may not be suitable for autologous TEBVs due to inadequate promotion of SMC migration and differentiation. PMID- 25119586 TI - Attachment styles and sexual dysfunctions: a case-control study of female and male sexuality. AB - The aim of this study was to investigate attachment styles in a group of women and men with sexual dysfunction. We recruited 44 subjects (21 women and 23 men) with sexual dysfunction and 41 subjects (21 women and 20 men) with healthy sexual function as the control group. Validated instruments for the evaluation of male and female sexual dysfunctions (M/F SD) and a psychometric tool specifically designed to investigate attachment style were administered. In women, significant differences were found between subjects with sexual dysfunction and healthy controls. The scales indicating an insecure attachment showed: discomfort with closeness (FSD = 42.85 +/- 11.55 vs CTRL = 37.38 +/- 8.54; P < 0.01), relationship as secondary (FSD = 26.76 +/- 2.60 vs CTRL = 18.42 +/- 7.99; P < 0.01), and need for approval (FSD=26.38 +/- 3.61 vs CTRL = 20.76 +/- 7.36; P < 0.01). Healthy women also had significantly higher scores in secure attachment (confidence: FSD = 24.57 +/- 3.89 vs CTRL = 33.42 +/- 5.74; P < 0.01). Men with sexual dysfunctions differed from healthy men in confidence (MSD = 30 +/- 6.33 vs CTRL = 36.05 +/- 5.26; P < 0.01) and in discomfort with closeness (MSD = 39.08 +/ 8 vs CTRL = 34.25 +/- 7.54; P < 0.05). These results suggest that particular aspects related to insecure attachment have a determinant role in people with sexual dysfunctions. It is therefore fundamental to identify the attachment styles and relational patterns in patients receiving counselling and psychological treatments focussed on sexual problems. PMID- 25119588 TI - Strong association of high urinary iodine with thyroid nodule and papillary thyroid cancer. AB - This study demonstrates a strong association of high urinary iodine with thyroid nodules and papillary thyroid cancer as well as aggressive cancer features, suggesting that high urinary iodine is a risk factor for thyroid cancer. The risk of high iodine intake for thyroid cancer has been suggested but not established. The objective of the study was to evaluate the relationship between urine iodine levels and thyroid nodule and thyroid cancer. We preoperatively tested fasting urine iodine in 154 thyroid nodule patients and correlated the results with pathological diagnoses and compared with 306 subjects as normal control. The median urine iodine (MUI) was 331.33 MUg/L in patients with benign thyroid nodules versus 466.23 MUg/L in patients with papillary thyroid cancer (PTC) (P=0.003), both of which were in the excessive iodine state and higher than the MUI of 174.30 MUg/L in the control group (P < 0.001), which was in the sufficient iodine state. Excessive iodine state (MUI>300 MUg/L) was seen in 62.75% of patients with benign thyroid nodules and 66.99% of patients with PTC, both of which were significantly higher than the iodine excessive rate of 19.93% in the control group (P<0.001). Moreover, MUI in patients with PTC with lymph node metastasis was significantly higher than that of PTC patients without lymph node metastasis (P<0.001). Urine iodine of thyroid cancer patients with stage III and IV disease was significantly higher than that of patients with stage I and II diseases (P<0.001). Multivariable analyses showed that, like sand calcification of thyroid nodule and TSH, urine iodine was an independent risk factor for PTC. These data demonstrate a significant association between high urinary iodine and benign and malignant thyroid nodules and PTC aggressiveness, supporting high urinary iodine as a risk factor for thyroid malignancy. Further studies are warranted to confirm these findings. PMID- 25119587 TI - Kruppel-like factor 5 as potential molecular marker in cervical cancer and the KLF family profile expression. AB - Cervical cancer (CC) as other cancer types, presents molecular deregulations, such as the alterations of transcription factors. Kruppel-like factors (KLF) are a family of transcriptional regulators. They are involved in diverse cellular processes, such as proliferation, apoptosis, and angiogenesis among others. Here, we analyzed the expression of all 17 KLF members at messenger RNA (mRNA) level, and protein expression of the two most commonly altered KLF5 and KLF6 in cervical tissues. Fifty-nine cervical tissues ranging from normal tissue to CC were evaluated for KLF1-17 mRNA expression by end-point RT-PCR and KLF5 by qRT-PCR. For KLF5 and KLF6 protein analysis, a tissue microarray was constructed containing the 59 cases and subjected for immunohistochemistry assay and KLF6 IVS1-27G>A single nucleotide polymorphism by direct DNA sequencing. KLF2-16 expressions were present in normal tissue, whereas all 17 were present in Low Grade Squamous Intraepithelial Lesion, High-Grade-SIL and CC, unrelated to presence of human papillomavirus (HPV). KLF5 mRNA expression gradually increased throughout the subgroups and overexpressed in CC (p=0.01). KLF5 and KLF6 proteins were immunodetected in all samples. For the KLF6 SNP analysis, 80% of the CC population analyzed presented GG genotype and the remaining 20% presented GA genotype (p=0.491). Our present data show that KLFs expression could not be related to HPV presence, at least at transcriptional level, and KLF5 mRNA overexpression could represent a potential molecular marker for CC; KLF6 SNP has no relation to increased risk of CC. PMID- 25119589 TI - Association between murine double minute 2 T309G polymorphism and risk of liver cancer. AB - During the past decade, a number of studies were published to evaluate the association between murine double minute 2 (MDM2) T309G polymorphism and risk of liver cancer. However, the association between MDM2 T309G polymorphism and risk of liver cancer was still unclear owing to the conflicting results from those published studies. An undated meta-analysis of all eligible studies was carried out to comprehensively assess the association. The pooled odds ratio (OR) with 95 % confidence interval (95% CI) was used to evaluate the association between MDM2 T309G polymorphism and risk of liver cancer. Finally, ten studies with a total of 2,243 cases and 3,471 controls were finally included into the meta-analysis. Overall, there was an association between MDM2 T309G polymorphism and risk of liver cancer (G vs. T: OR=1.39, 95% CI 1.17-1.64, P<0.001; GG vs. TT: OR=1.87, 95% CI 1.34-2.62, P<0.001; GG/GT vs. TT: OR=1.61, 95 % CI 1.24-2.08, P<0.001). Subgroup analysis in Europeans showed that there was also an association between MDM2 T309G polymorphism and risk of liver cancer in Europeans (G vs. T: OR=1.81, 95% CI 1.45-2.27, P<0.001; GG vs. TT: OR=3.26, 95% CI 1.99-5.32, P<0.001; GG/GT vs. TT: OR=2.20, 95% CI 1.58-3.07, P<0.001). Subgroup analysis in Asians showed that there was also an association between MDM2 T309G polymorphism and risk of liver cancer in Asians (G vs. T: OR=1.27, 95% CI 1.06-1.52, P=0.010; GG vs. TT: OR=1.59, 95% CI 1.11-2.27, P=0.011; GG/GT vs. TT: OR=1.41, 95% CI 1.07-1.87, P=0.016). The meta-analysis provides a strong evidence for the association between MDM2 T309G polymorphism and risk of liver cancer. PMID- 25119590 TI - Molecular regulation of ovarian cancer cell invasion. AB - The molecular mechanism underlying ovarian cancer invasiveness and metastasis remains unclear. Since significant downregulation in microRNA 200 (miRNA200) family (miR200a, miR200b, and miR200c) has been reported in the invasive ovarian cancer cells, here, we used two human ovarian cancer cell lines, OVCAR3 and SKOV3, to study the molecular basis of miR200, matrix metalloproteinase 3 (MMP3) activation, and cancer invasiveness. We found that overexpression of either miR200 family member in OVCAR3 or SKOV3 cells significantly inhibited production and secretion of MMP3 and cancer invasiveness. Moreover, forced MMP3 expression abolished miR200-induced inhibition of ovarian cancer cell invasiveness, suggesting that miR200 family inhibited ovarian cell invasiveness via downregulating MMP3. Furthermore, ZEB1, a major target of miR200, was inhibited by miR200 overexpression. Forced ZEB1 expression abolished miR200-induced inhibition of ovarian cancer cell invasiveness, suggesting that ZEB1 is a direct target of miR200 for inhibiting ovarian cell invasiveness. Finally, phosphorylated SMAD3 (pSMAD3), a major partner of ZEB1, was efficiently inhibited by miR200, which could be restored by forced expression of ZEB1, but not by forced expression of MMP3, suggesting that ZEB1/pSMAD3 is signaling cascade upstream of MMP3 in this model. Taken together, our data suggest that miR200 family inhibited ovarian cancer cell invasiveness and metastasis by downregulating MMP3, possibly through ZEB1/pSMAD3. PMID- 25119591 TI - Novel methodologies in analysis of small molecule biomarkers and living cells. AB - Enzyme-linked immuno-sorbent assay (ELISA) is widely used for biomarker detection. A good biomarker can distinguish patients from healthy or benign diseases. However, the ELISA method is not suitable for small molecule or trace substance detection. Along with the development of new technologies, an increasing level of biomaterials, especially small molecules, will be identified as novel biomarkers. Quantitative immuno-PCR, chromatography-mass spectrometry, and nucleic acid aptamer are emerging methodologies for detection of small molecule biomarkers, even in living cells. In this review, we focus on these novel technologies and their potential for small molecule biomarkers and living cell analysis. PMID- 25119593 TI - Different mutational characteristics of TSG in cell lines and surgical specimens. AB - One of the most crucial concerns of cancer research pertains to the differences between the neoplastic cells in tumor specimens in vivo and their counterparts in cell lines. The huge amount of results deposited in cancer genetic databases allows to address this issue from a wider perspective. Our analysis of the Sanger Institute Catalog Of Somatic Mutations In Cancer (COSMIC) database v61 showed a lower percentage of homozygous mutations in a group of tumor suppressor genes in surgical samples (in vivo) in comparison to their frequency in cell lines (in vitro). Similarly, the mutations resulting in the lack of protein (e.g., nonsense mutations or whole gene deletions) of several tumor suppressor genes (TSGs) were more frequently observed in vitro than in vivo. In this article, we suggest two potential explanations of these data. Firstly, TSG heterozygous mutations resulting in the modified protein (e.g., missense mutations) may be gradually (when the specific molecular context is achieved) changed to homozygous mutations resulting in the lack of protein during carcinogenesis. Secondly, among different independent pathways of tumorigenesis, those leading to homozygous nonsense mutations are characteristic for cells which are more efficiently stabilized in vitro. To conclude, these observations may be interesting for researchers working with cell line in vitro models illustrating the extent to which they reflect the tumors in vivo. PMID- 25119592 TI - Adjuvant and chemopreventive therapies for resectable hepatocellular carcinoma: a literature review. AB - The recurrence rate of hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR) is very high. Many clinical trials have explored the efficacy of several treatment modalities to prevent recurrence, including adjuvant and chemopreventive therapy, but they have often reported contradictory findings. As a result, most liver guidelines and liver seminars do not unequivocally endorse adjuvant or chemopreventive therapy for HCC patients after potentially curative HR. To examine the available evidence on this question, we comprehensively searched PubMed for controlled studies that included a supportive care or placebo control arm, and we used the GRADE system to classify and assess the results. PMID- 25119594 TI - Hsa-miR-195 targets PCMT1 in hepatocellular carcinoma that increases tumor life span. AB - MicroRNAs are small 19-25 nucleotides which have been shown to play important roles in the regulation of gene expression in many organisms. Downregulation or accumulation of miRNAs implies either tumor suppression or oncogenic activation. In this study, differentially expressed hsa-miR-195 in hepatocellular carcinoma (HCC) was identified and analyzed. The prediction was done using a consensus approach of tools. The validation steps were done at two different levels in silico and in vitro. FGF7, GHR, PCMT1, CITED2, PEX5, PEX13, NOVA1, AXIN2, and TSPYL2 were detected with high significant (P < 0.005). These genes are involved in important pathways in cancer like MAPK signaling pathway, Jak-STAT signaling pathways, regulation of actin cytoskeleton, angiogenesis, Wnt signaling pathway, and TGF-beta signaling pathway. In vitro target validation was done for protein-L isoaspartate (D-aspartate) O-methyltransferase (PCMT1). The co-transfection of pmirGLO-PCMT1 and pEGP-miR-195 showed highly significant results. Firefly luciferase was detected using Lumiscensor and t test analysis was done. Firefly luciferase expression was significantly decreased (P < 0.001) in comparison to the control. The low expression of firefly luciferase validates the method of target prediction that we used in this work by working on PCMT1 as a target for miR-195. Furthermore, the rest of the predicted genes are suspected to be real targets for hsa-miR-195. These target genes control almost all the hallmarks of liver cancer which can be used as therapeutic targets in cancer treatment. PMID- 25119595 TI - Podoplanin expressing cancer-associated fibroblasts in oral cancer. AB - Podoplanin is a mucin-type glycoprotein widely used as a lymphatic endothelial marker. It is well known that podoplanin is expressed in various neoplasms including oral squamous cell carcinoma (OSCC). Apart from podoplanin expression in cancer cells, recent studies have suggested that podoplanin expression in stromal cancer-associated fibroblasts (CAFs) may be an indicator of poor prognosis in various cancers. In the present study, we performed immunohistochemical analyses of podoplanin and alpha-smooth muscle actin (alpha SMA) in OSCC in order to clarify the significance of podoplanin-positive CAFs. Paraffin-embedded tissue specimens of 69 primary and 29 corresponding metastatic lesions in lymph nodes were examined immunohistochemically using antibodies against podoplanin and alpha-SMA. Podoplanin-positive stromal fibroblasts were detected in 51 (73.9%) of the 69 primary OSCCs and 24 (82.8%) of the 29 lymph nodes metastases. alpha-SMA immunoreactivity was observed in 39 (56.5%) of the primaries and 24 (82.8%) of the metastases. Further examination showed that 38 (74.5%) of the primary lesions and 23 (95.8%) of the metastases with podoplanin positivity were also positive for alpha-SMA. In addition, the intensity of alpha SMA immunoreactivity increased as that of podoplanin became stronger. Podoplanin positive CAFs are considered to be myofibroblasts that may contribute to progression of oral cancer. PMID- 25119597 TI - Analysis of Tim-3 as a therapeutic target in prostate cancer. AB - T cell immunoglobulin domain and mucin domain-containing molecule 3 (Tim-3) is a newly discovered immunomodulatory, which plays an important role in immunity regulation. Recent evidence suggests that Tim-3 is differentially regulated in a variety of tumors and has a potential as a therapeutic target. The aim of this study was to investigate the effect of Tim-3 on the development of prostate cancer (PCa). Tim-3 expressing on peripheral CD4+ T and CD8+ T cells was analyzed by flow cytometry. The relationships between Tim-3 expression and clinicopathological features were analyzed. Immunohistochemical expression of Tim 3 was examined in our large numbers of paraffin-fixed prostate tissues. Flow cytometry revealed that expression of Tim-3 was significantly increased on both CD4+ and CD8+ T cells in PCa patients than that in benign prostate hyperplasia (BPH) patients. Also, the level of Tim-3 on CD4+ T cells was positively correlated with CD8+ T cells in patients. Further analyses revealed that the levels of Tim-3 on CD4+ T cells and CD8+ T cells exhibited different expression patterns in terms of localization depending on pathological category of PCa and metastasis. Immunohistochemical analysis revealed that positive staining of Tim-3 in PCa but little or no staining of Tim-3 was observed in BPH epithelium. Tim-3 may affect the development and progression of PCa, which may provide knowledge for using Tim-3 as a novel therapy for effective PCa management. PMID- 25119598 TI - Downregulation of a long noncoding RNA-ncRuPAR contributes to tumor inhibition in colorectal cancer. AB - In recent years, the role of long noncoding RNAs (lncRNAs) in cancer is increasingly focused. ncRuPAR is a newly detected lncRNA; in previous study, we found out that ncRuPAR could inhibit tumor progression by downregulating protease activated receptor-1 (PAR-1), but its role in colorectal cancer (CRC) is never elucidated. Here, we conducted a self-control study which includes 105 CRC samples. By quantitative real time PCR (qRT-PCR) and immunohistochemical staining, we detected the expression of ncRuPAR and PAR-1 as well as their correlation; we further associated these data with the clinicopathologic parameters. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of ncRuPAR and PAR-1, respectively. Our results indicated that the expression of ncRuPAR was significantly downregulated in CRC compared with paired adjacent nontumor tissues, but the level of PAR-1 mRNA in cancerous tissues was significantly higher than in adjacent normal areas. The expression of ncRuPAR was significantly correlated with lymph node metastasis, distant metastasis, Duck's stage, differentiation, and TNM stage and was potentially negatively associated with the mRNA levels and EI scores of PAR-1. The area under the ROC curve of ncRuPAR was 0.81 (95% confidence interval (CI): 0.75-0.87); at a cutoff value of 8.34, the ncRuPAR measurement had a sensitivity of 97.14%, a specificity of 65.87%, and an accuracy of 82.86% to predict CRC. PMID- 25119596 TI - The clinical significance and regulation mechanism of hypoxia-inducible factor-1 and miR-191 expression in pancreatic cancer. AB - The aim of study was to discuss the correlation and regulatory mechanism of HIF-1 and miR-191 expression in pancreatic tumor. The association between the miR-191 and the clinicopathologic characteristics and the prognosis of pancreatic cancer was further explored. After hypoxic cultured for 6 and 12 h, qRT-PCR and Western blot were practiced to analyze the miR-191 and HIF-1 expression of MIA PaCa-2 and Aspac1 cells. We regulated the HIF-1 expression via plasmid and siRNA transfection to observe the alteration of HIF-1 and miR-191 expression. ChIP sequencing identified the binding sites of HIF-1 and miR-191. Dual luciferase assays were practiced to verify the binding sites. Immunohistochemical staining was practiced to analyze the expression of HIF-1, while qRT-PCR were done for investigating miR-191 in tumor tissues. Then, the association between the expression of them and the clinicopathologic characteristics and prognosis of pancreatic cancer were analyzed. After hypoxic cultured 12 h, the expression of HIF-1 protein, HIF-1mRNA and miR-191 of MIA PaCa-2 and AsPC-1 cells increased significantly (P < 0.05). After HIF-1 overexpressing plasmid transfected to the MIA PaCa-2 and AsPC-1 cells for 48 h, the expression of HIF-1 protein, HIF-1mRNA, and miR-191 upregulated significantly (P < 0.05). While after transfected the MIA PaCa-2 cells by HIF-1 siRNA, the significant decreasing of HIF-1 protein, HIF 1mRNA, and miR-191 expression were observed (P < 0.05). ChIP sequencing showed the protein synthesis of HIF-1 increased in hypoxia situation. Only the HRE5 ( 1,169 bp, ChIP4) were significantly brighter in hypoxia in comparing with normoxic cells. In dual luciferase assays, after pGL3-miR-191 and HIF-1 overexpressing plasmid co-transfect the MIAPaCa-2 cells for 48 h, its relative expression of bioluminescence was higher than those co-transfected by mutant miR 191 vectors and HIF-1 overexpressing plasmid or by pGL3-miR-191 and HIF-1 empty plasmid. The expression of miR-191 closely associated with the tumor size, pTNM stage, lymph node metastasis, and perineural invasion (P < 0.05). Patients with higher expression of miR-191 were a risk factor for prognosis of pancreatic cancers. Expression of HIF-1 in pancreatic cancer cells increased under the condition of chronic hypoxia, which may bind to HRE2 in 5'flanking region of miR 191 and initiate transcription of miR-191. Expression of miR-191 was significantly higher in pancreatic tumor tissues. The expression of miR-191 closely associated with the tumor size, pTNM stage, lymph node metastasis and perineural invasion and poor prognosis of pancreatic cancer. PMID- 25119599 TI - miR-152 suppresses gastric cancer cell proliferation and motility by targeting CD151. AB - We aimed to study the post-translational regulation of CD151 by the microRNA miR 152. CD151 is highly expressed in gastric cancer (GC) and has been shown to accelerate GC by enhancing invasion and metastasis; however, its regulation is still unclear. Our results showed decreased expression of miR-152 in GC tissue samples and cell lines. In addition, miR-152 complementation significantly inhibits both the proliferation and motility of GC cells. CD151 was found to be a target of miR-152, and overexpression of CD151 attenuated the suppressive effect of miR-152. Our findings highlight an essential role of miR-152 in the regulation of proliferation and motility of GC cells and suggest a potential application of miR-152 in GC treatment. PMID- 25119600 TI - TES was epigenetically silenced and suppressed the epithelial-mesenchymal transition in breast cancer. AB - The TES gene was frequently lost in breast cancer, which could inhibit tumor invasion and the formation of distant metastasis. However, the underlying mechanisms remain unknown yet. In the present study, we aimed to investigate how TES was silenced and its roles in EMT--the key step for tumor metastasis. Real time polymerase chain reaction (PCR) and Western blot were used to detect the mRNA and protein expression of target genes; the status of TES promoter was determined by methylation-specific PCR and subsequently, DNA sequencing. Overexpression or downregulation of TES was achieved by pcDNA3.1-TES or shRNA-TES transfection. Cellular adhesion and migration were investigated by the adhesion and Transwell assays. Morphological changes of breast cancer cells were observed under the optical microscope. The Rho A activity was measured using a commercial kit, and its roles in TES-manipulated EMT were determined by real-time PCR and Western blot. The 42.3% (33/78) breast cancer tissues presented hypermethylation of the TES gene, whereas only 2 (2.6%) non-malignant cases were hypermethylated (P<0.001). Moreover, TES hypermethylation was significantly correlated with larger tumor diameter (P=0.03) and lympho node metastasis (P=0.024). In primary cultured breast cancer cells, the demethylation treatment using 5-aza-dC notably restored the expression of TES. In vitro, overexpression of TES enhanced cellular adhesion inhibited migration and suppressed EMT, while downregulation of TES impaired cellular adhesion, promoted migration, and enhanced EMT. TES overexpression also activated the Rho A signal, which is a critical factor for the effects of TES on the EMT procedure. We firstly proved that frequent loss of TES in breast cancer was caused by promoter hypermethylation, which was correlated with poor prognosis. In vitro, TES enhanced cellular adhesion, suppressed tumor migration, and inhibited EMT. Moreover, the Rho A pathway was critical for the effects of TES on EMT, which can be blocked by the Rho A inhibitor. Therefore, we propose restoration of TES as a potent strategy for breast cancer therapy. PMID- 25119601 TI - Armc8 expression was elevated during atypia-to-carcinoma progression and associated with cancer development of breast carcinoma. AB - Armadillo repeat-containing protein 8 (Armc8) is a key factor to regulate cell membrane adhesion complex through promoting alpha-catenin degradation. However, its expression and function in human malignant tumors are largely unknown. Here, we present our study investigating Armc8 expression in tumor and non-tumor breast tissues including 45 normal epithelia, 53 lesions of hyperplasia with or without dysplasia, 22 benign tumors, and 92 carcinomas including 28 carcinomas in situ and 64 infiltrating carcinomas using immunohistochemistry (IHC) and Western blotting study. Armc8 expression was detected mainly in the cytoplasm with occasional membrane immunostaining. The positive rate of Armc8 expression in normal breast epithelia (8.9%, four out of 45) was very low. No significant difference was found between Armc8 expression in usual ductal hyperplasia (UDH) (11.1%, two out of 18), benign breast tumors including intraductal papilloma (10.0%, one out of 10) and fibroadenoma (8.3%, one out of 12), and normal breast epithelia (p>0.05). Elevated expression of Armc8 was found in breast epithelia with dysplasia (24.0%, six out of 25) compared to that in normal breast epithelia, UDH, and benign breast tumors (p<0.05). Armc8 expression in breast carcinoma including breast carcinoma in situ (10/28, 35.7%), infiltrating ductal carcinoma (60.7%, 34/56), and infiltrating lobular carcinoma (50.0%, 4/8) was higher than that in normal breast epithelia, UDH, benign breast tumors, and breast epithelia with dysplasia (p<0.05). The highest expression of Armc8 was found in infiltrating breast carcinoma (59.4%, 38/64) compared to all the other breast tissues. Higher Armc8 expression was found to be linked to lymph node metastasis and advanced tumor-node-metastasis (TNM) stages (III+IV) in infiltrating breast carcinoma (p<0.05). We further confirmed Armc8 expression in breast epithelial cell line MCF10A and breast carcinoma cell lines including MCF 7, MDA-MB-231, and ZR751 using Western blotting and immunofluorescent study. These results indicate that the elevated expression of Armc8 may be involved in carcinogenesis including atypia-to-carcinoma progression and cancer development of breast carcinoma. PMID- 25119603 TI - In Vitro and in vivo characterization of wireless and passive micro system enabling gastrointestinal pressure monitoring. AB - This paper presents a wireless and passive micro pressure system based on the LC mutual inductance detection mechanism for gastrointestinal (GI) pressure monitoring. The micro pressure system is composed of a sensor capsule (a pressure sensitive micro capacitive sensor in series with an induction coil to form an LC tank) and a detection unit (a detection coil connected with a network analyzer). The pressure variations under measurement lead to changes in the capacitance of the pressure sensor and therefore a shift in the LC tank resonant frequency, quantified by the impedance measurement of the detection coil. The pressure sensor was fabricated using microfabrication processes with key parameters optimized. The in vitro characterization of the micro pressure system recorded a sensitivity of 0.2491 kHz/kPa (-10 kPa to 30 kPa). One-month rabbit stomach pressure monitoring was conducted based on the developed micro pressure system as a confirmation of device long term in vivo stability. Furthermore, rabbit stomach pressure variations before and after food feeding was recorded and compared where three distinctive contraction patterns (random contraction with low amplitude, irregular strong contractions and regular contraction in a cyclic manner) following food feeding were located. Compared to previous reported GI pressure sensors, this LC tank is featured with simple device structure without batteries and electrical components for energy transfer. Both in vitro and in vivo characterization confirm the functionality of the system, which may enable the gastrointestinal motility study in the near future. PMID- 25119602 TI - Chronic atrophic gastritis in association with hair mercury level. AB - The objective of this study was to explore hair mercury level in association with chronic atrophic gastritis, a precancerous stage of gastric cancer (GC), and thus provide a brand new angle of view on the timely intervention of precancerous stage of GC. We recruited 149 healthy volunteers as controls and 152 patients suffering from chronic gastritis as cases. The controls denied upper gastrointestinal discomforts, and the cases were diagnosed as chronic superficial gastritis (n=68) or chronic atrophic gastritis (n=84). We utilized Mercury Automated Analyzer (NIC MA-3000) to detect hair mercury level of both healthy controls and cases of chronic gastritis. The statistic of measurement data was expressed as mean +/- standard deviation, which was analyzed using Levene variance equality test and t test. Pearson correlation analysis was employed to determine associated factors affecting hair mercury levels, and multiple stepwise regression analysis was performed to deduce regression equations. Statistical significance is considered if p value is less than 0.05. The overall hair mercury level was 0.908949 +/- 0.8844490 ng/g [mean +/- standard deviation (SD)] in gastritis cases and 0.460198 +/- 0.2712187 ng/g (mean+/-SD) in healthy controls; the former level was significantly higher than the latter one (p=0.000<0.01). The hair mercury level in chronic atrophic gastritis subgroup was 1.155220 +/- 0.9470246 ng/g (mean +/- SD) and that in chronic superficial gastritis subgroup was 0.604732 +/- 0.6942509 ng/g (mean +/- SD); the former level was significantly higher than the latter level (p<0.01). The hair mercury level in chronic superficial gastritis cases was significantly higher than that in healthy controls (p<0.05). The hair mercury level in chronic atrophic gastritis cases was significantly higher than that in healthy controls (p<0.01). Stratified analysis indicated that the hair mercury level in healthy controls with eating seafood was significantly higher than that in healthy controls without eating seafood (p<0.01) and that the hair mercury level in chronic atrophic gastritis cases was significantly higher than that in chronic superficial gastritis cases (p<0.01). Pearson correlation analysis indicated that eating seafood was most correlated with hair mercury level and positively correlated in the healthy controls and that the severity of gastritis was most correlated with hair mercury level and positively correlated in the gastritis cases. Multiple stepwise regression analysis indicated that the regression equation of hair mercury level in controls could be expressed as 0.262 multiplied the value of eating seafood plus 0.434, the model that was statistically significant (p<0.01). Multiple stepwise regression analysis also indicated that the regression equation of hair mercury level in gastritis cases could be expressed as 0.305 multiplied the severity of gastritis, the model that was also statistically significant (p<0.01). The graphs of regression standardized residual for both controls and cases conformed to normal distribution. The main positively correlated factor affecting the hair mercury level is eating seafood in healthy people whereas the predominant positively correlated factor affecting the hair mercury level is the severity of gastritis in chronic gastritis patients. That is to say, the severity of chronic gastritis is positively correlated with the level of hair mercury. The incessantly increased level of hair mercury possibly reflects the development of gastritis from normal stomach to superficial gastritis and to atrophic gastritis. The detection of hair mercury is potentially a means to predict the severity of chronic gastritis and possibly to insinuate the environmental mercury threat to human health in terms of gastritis or even carcinogenesis. PMID- 25119604 TI - Adverse effects of prohibiting narrow provider networks. AB - Many insurers participating in the new insurance exchanges are controlling costs by offering plans with narrow provider networks. Proposed regulations would promote network adequacy, but a pro-provider stance may not be inherently pro consumer or even pro-patient. PMID- 25119605 TI - Genotype-phenotype correlation--promiscuity in the era of next-generation sequencing. AB - Newly cost-effective next-generation sequencing has led to an explosion of discoveries of novel genetic mutations that reveal the rampant "promiscuity" of genotype-phenotype relationships. Such discoveries should ultimately revolutionize clinical care. PMID- 25119609 TI - Efficacy of high-dose versus standard-dose influenza vaccine in older adults. AB - BACKGROUND: As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness. METHODS: We conducted a phase IIIb-IV, multicenter, randomized, double-blind, active controlled trial to compare IIV3-HD (60 MUg of hemagglutinin per strain) with standard-dose trivalent, inactivated influenza vaccine (IIV3-SD [15 MUg of hemagglutinin per strain]) in adults 65 years of age or older. Assessments of relative efficacy, effectiveness, safety (serious adverse events), and immunogenicity (hemagglutination-inhibition [HAI] titers) were performed during the 2011-2012 (year 1) and the 2012-2013 (year 2) northern-hemisphere influenza seasons. RESULTS: A total of 31,989 participants were enrolled from 126 research centers in the United States and Canada (15,991 were randomly assigned to receive IIV3-HD, and 15,998 to receive IIV3-SD). In the intention-to-treat analysis, 228 participants in the IIV3-HD group (1.4%) and 301 participants in the IIV3-SD group (1.9%) had laboratory-confirmed influenza caused by any viral type or subtype associated with a protocol-defined influenza-like illness (relative efficacy, 24.2%; 95% confidence interval [CI], 9.7 to 36.5). At least one serious adverse event during the safety surveillance period was reported by 1323 (8.3%) of the participants in the IIV3-HD group, as compared with 1442 (9.0%) of the participants in the IIV3-SD group (relative risk, 0.92; 95% CI, 0.85 to 0.99). After vaccination, HAI titers and seroprotection rates (the percentage of participants with HAI titers >= 1:40) were significantly higher in the IIV3-HD group. Conclusions: Among persons 65 years of age or older, IIV3-HD induced significantly higher antibody responses and provided better protection against laboratory-confirmed influenza illness than did IIV3-SD. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01427309.). PMID- 25119610 TI - Clinical practice: Obsessive-compulsive disorder. AB - A 19-year-old man is brought to his primary physician by his father, who explains that his son washes his hands a hundred times a day, will not touch anything that has been touched by someone else without scrubbing it first, and has a fear of germs that has left him isolated in his bedroom, unable to eat, and wishing he were dead. Although the father reports that his son has always been finicky, this problem started approximately 2 years ago and has gradually become completely disabling. How should this patient be evaluated and treated? PMID- 25119611 TI - Syndromes of thrombotic microangiopathy. AB - This review article covers the diverse pathophysiological pathways that can lead to microangiopathic hemolytic anemia and a procoagulant state with or without damage to the kidneys and other organs. PMID- 25119612 TI - Images in clinical medicine: Syphilitic gumma. AB - A 45-year-old woman presented to a clinic in rural Uganda with a 1-year history of a progressively enlarging ulcerated mass on the hard palate. The mass had initially been painless but recently had become painful and was causing difficulty in speaking and swallowing. PMID- 25119608 TI - Global sodium consumption and death from cardiovascular causes. AB - BACKGROUND: High sodium intake increases blood pressure, a risk factor for cardiovascular disease, but the effects of sodium intake on global cardiovascular mortality are uncertain. METHODS: We collected data from surveys on sodium intake as determined by urinary excretion and diet in persons from 66 countries (accounting for 74.1% of adults throughout the world), and we used these data to quantify the global consumption of sodium according to age, sex, and country. The effects of sodium on blood pressure, according to age, race, and the presence or absence of hypertension, were calculated from data in a new meta-analysis of 107 randomized interventions, and the effects of blood pressure on cardiovascular mortality, according to age, were calculated from a meta-analysis of cohorts. Cause-specific mortality was derived from the Global Burden of Disease Study 2010. Using comparative risk assessment, we estimated the cardiovascular effects of current sodium intake, as compared with a reference intake of 2.0 g of sodium per day, according to age, sex, and country. RESULTS: In 2010, the estimated mean level of global sodium consumption was 3.95 g per day, and regional mean levels ranged from 2.18 to 5.51 g per day. Globally, 1.65 million annual deaths from cardiovascular causes (95% uncertainty interval [confidence interval], 1.10 million to 2.22 million) were attributed to sodium intake above the reference level; 61.9% of these deaths occurred in men and 38.1% occurred in women. These deaths accounted for nearly 1 of every 10 deaths from cardiovascular causes (9.5%). Four of every 5 deaths (84.3%) occurred in low- and middle-income countries, and 2 of every 5 deaths (40.4%) were premature (before 70 years of age). The rate of death from cardiovascular causes associated with sodium intake above the reference level was highest in the country of Georgia and lowest in Kenya. CONCLUSIONS: In this modeling study, 1.65 million deaths from cardiovascular causes that occurred in 2010 were attributed to sodium consumption above a reference level of 2.0 g per day. (Funded by the Bill and Melinda Gates Foundation.). PMID- 25119613 TI - Case Records of the Massachusetts General Hospital. Case 25-2014. A 37-year-old man with ulcerative colitis and bloody diarrhea. AB - A 37-year-old man with ulcerative colitis was admitted to the hospital because of abdominal cramping, diarrhea, hematochezia, fever to a peak temperature of 38.8 degrees C, and drenching night sweats. Several weeks earlier, he had performed home fecal transplantation. PMID- 25119614 TI - Low sodium intake--cardiovascular health benefit or risk? PMID- 25119606 TI - Association of urinary sodium and potassium excretion with blood pressure. AB - BACKGROUND: Higher levels of sodium intake are reported to be associated with higher blood pressure. Whether this relationship varies according to levels of sodium or potassium intake and in different populations is unknown. METHODS: We studied 102,216 adults from 18 countries. Estimates of 24-hour sodium and potassium excretion were made from a single fasting morning urine specimen and were used as surrogates for intake. We assessed the relationship between electrolyte excretion and blood pressure, as measured with an automated device. RESULTS: Regression analyses showed increments of 2.11 mm Hg in systolic blood pressure and 0.78 mm Hg in diastolic blood pressure for each 1-g increment in estimated sodium excretion. The slope of this association was steeper with higher sodium intake (an increment of 2.58 mm Hg in systolic blood pressure per gram for sodium excretion >5 g per day, 1.74 mm Hg per gram for 3 to 5 g per day, and 0.74 mm Hg per gram for <3 g per day; P<0.001 for interaction). The slope of association was steeper for persons with hypertension (2.49 mm Hg per gram) than for those without hypertension (1.30 mm Hg per gram, P<0.001 for interaction) and was steeper with increased age (2.97 mm Hg per gram at >55 years of age, 2.43 mm Hg per gram at 45 to 55 years of age, and 1.96 mm Hg per gram at <45 years of age; P<0.001 for interaction). Potassium excretion was inversely associated with systolic blood pressure, with a steeper slope of association for persons with hypertension than for those without it (P<0.001) and a steeper slope with increased age (P<0.001). CONCLUSIONS: In this study, the association of estimated intake of sodium and potassium, as determined from measurements of excretion of these cations, with blood pressure was nonlinear and was most pronounced in persons consuming high-sodium diets, persons with hypertension, and older persons. (Funded by the Heart and Stroke Foundation of Ontario and others.). PMID- 25119615 TI - Bariatric surgery versus intensive medical therapy for diabetes. PMID- 25119616 TI - Bariatric surgery versus intensive medical therapy for diabetes. PMID- 25119617 TI - Bariatric surgery versus intensive medical therapy for diabetes. PMID- 25119618 TI - Bariatric surgery versus intensive medical therapy for diabetes. PMID- 25119607 TI - Urinary sodium and potassium excretion, mortality, and cardiovascular events. AB - BACKGROUND: The optimal range of sodium intake for cardiovascular health is controversial. METHODS: We obtained morning fasting urine samples from 101,945 persons in 17 countries and estimated 24-hour sodium and potassium excretion (used as a surrogate for intake). We examined the association between estimated urinary sodium and potassium excretion and the composite outcome of death and major cardiovascular events. RESULTS: The mean estimated sodium and potassium excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference range), a higher estimated sodium excretion (>= 7.00 g per day) was associated with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence interval [CI], 1.02 to 1.30), as well as increased risks of death and major cardiovascular events considered separately. The association between a high estimated sodium excretion and the composite outcome was strongest among participants with hypertension (P=0.02 for interaction), with an increased risk at an estimated sodium excretion of 6.00 g or more per day. As compared with the reference range, an estimated sodium excretion that was below 3.00 g per day was also associated with an increased risk of the composite outcome (odds ratio, 1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a reduced risk of the composite outcome. CONCLUSIONS: In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day and 6 g per day was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events. (Funded by the Population Health Research Institute and others.). PMID- 25119619 TI - Bariatric surgery versus intensive medical therapy for diabetes. PMID- 25119620 TI - Aortic dilatation with bicuspid aortic valve. PMID- 25119622 TI - Lyme disease. PMID- 25119623 TI - Lyme disease. PMID- 25119621 TI - Lyme disease. PMID- 25119624 TI - Activated protein C resistance assay and factor V Leiden. AB - The authors suggest that functional testing for activated protein C resistance is cheaper and more clinically relevant than genetic testing to detect a factor V Leiden mutation in identifying persons who are at risk for thromboembolism. PMID- 25119625 TI - Images in clinical medicine: Morphologic changes in erythrocytes in hypertriglyceridemia. AB - A 39-year-old woman with a history of gestational diabetes was admitted with epigastric pain from acute pancreatitis. She had no history of hyperlipidemia, but multiple blood samples were grossly lipemic, and serum triglyceride levels were markedly increased. PMID- 25119626 TI - Reinforcement with fascia lata as an alternative in the repair of chronic quadriceps tendon injuries. PMID- 25119627 TI - The Role and Influence of Faith Leaders on Health-Related Issues and Programs in their Congregation. AB - This qualitative study explored the influence of faith leaders on health-related issues within their congregation. Semi-structured interviewers with 24 faith leaders found that chronic conditions and poor health behaviors were the top health challenges facing their congregation. A majority mentioned health-related activities taking place at their church. Most believed they had influence on their congregation for issues related to health/wellness, most commonly in the form of increasing awareness. A majority talked about the importance of being a role model. It is important to understand how to most effectively capitalize on the strengths of and engage pastors in health promotion efforts. PMID- 25119628 TI - Increased congregational support for parents of children with cystic fibrosis. AB - Positive health outcomes are related to adults' religious congregational participation. For parents of children with chronic disease, structured daily care routines and/or strict infection control precautions may limit participation. For this exploratory study, we examined the relationship between congregational support and religious coping by parents of children with cystic fibrosis (CF) compared to parents for whom child health issues were not significant stressors. CF parents reported higher levels of emotional support from congregation members and use of religious coping. Within-group differences were found for CF parents by denominational affiliation. Congregational support for parents dealing with child chronic disease is important. PMID- 25119629 TI - [Heatstroke in dogs in southern Germany. A retrospective study over a 5.5-year period]. AB - OBJECTIVE: Heatstroke is a life-threating emergency in dogs. The aim of this retrospective study was to analyse the sources of heat stroke in dogs, predisposing and prognostic factors, results of physical examination and clinical pathology as well as the course of this condition and appropriate treatment. MATERIAL AND METHODS: Patient histories of 12 dogs diagnosed with heat stroke over a 5.5-year period were analysed retrospectively. Normality was tested using the Kolmogrow-Smirnow Test and analysed using T-tests, the Chi-square test and the Mann-Whitney U-test. P-values < 0.05 were considered significant. RESULTS: Heat stroke occurred most frequently during summer, particularly in the afternoon. The most common cause of heat stroke was heat exposition in a car. Brachycephalic breeds were overrepresented. The most common clinical signs were polypnoea, tachycardia, hyperthermia and depression to prostration as well as gastrointestinal and neurological symptoms. Clinical pathology results included haemoconcentration, thrombocytopenia, hyperkalemia, prolonged activated partial thromboplastin time and azotemia. Therapies employed included oxygen application, cooling, fluid therapy and administration of gastrointestinal protectants, antiemetics and antibiotics. Duration of hospitalization was 1-6 days. The overall mortality rate was 50%. Most of the non-survivors died or were euthanized within 24-48 hours after presentation. All animals remaining alive after 3 days survived and could be discharged from hospital. CLINICAL RELEVANCE: Heat stroke is a life-threating condition, which can lead to shock, sepsis, coagulation disorders and multiorgan failure. Early recognition and appropriate treatment are important factors for a positive outcome. Furthermore, intensive monitoring and rapid therapy adaption as required are pivotal. PMID- 25119631 TI - Feline lower urinary tract disease in a German cat population. A retrospective analysis of demographic data, causes and clinical signs. AB - OBJECTIVE: To investigate epidemiologic data, clinical signs, results of urinalysis and causes of lower urinary tract disease in a German veterinary hospital population of cats and to determine if the demographic data, history, clinical signs and urinalysis results correlate with a particular etiology. MATERIALS AND METHODS: Cats presented with signs of feline lower urinary tract disease (FLUTD) with a documented history and physical examination, a complete urinalysis (urine specific gravity, urine dipstick and sediment, urine culture) of urine obtained by cystocentesis or catheterization, and diagnostic imaging of the urinary tract were included into the study. Cats that had received a previous treatment during the same episode of FLUTD were excluded. RESULTS: A total of 302 cats were included into the study. Cats with FLUTD presented throughout the seasons with similar frequency. The most common diagnosis was feline idiopathic cystitis (FIC) (55.0%), followed by bacterial urinary tract infection (UTI) (18.9%), urethral plug (10.3%) and urolithiasis (7.0%). Urethral obstruction was significantly more frequent in cats with FIC than in cats with UTI. Cats with FIC and urethral plugs were significantly younger and had significantly higher body weights than cats with UTI and neoplasia. FIC and urethral plugs were significantly more common causes of FLUTD in cats younger than 10 years compared to cats that were 10 years or older (65.2% versus [vs.] 35.8% and 13.3% vs. 3.0%), while the incidences of UTI and neoplasia increased with age (12.9% vs. 41.8% and 1.0% vs. 13.4%). CONCLUSION AND CLINICAL RELEVANCE: FIC and UTI are the most common diagnoses in cats with FLUTD, with a significant age-related difference in incidence. PMID- 25119632 TI - [New drugs for small animals in 2013]. AB - In 2013, four active pharmaceutical ingredients were released on the German market for small animals. Those are the recombinant human bone morphogenetic protein-2 dibotermin alfa (TruScient(r)), the ectoparasiticide of the oxadiazine group indoxacarb (Activyl(r)), the antiepileptic imepitoin (Pexion(r)) and the angiotensin-II1-receptor antagonist telmisartan (Semintra(r)). One substance was authorized for an additional species. The prolactin antagonist cabergoline is now also authorized for use in cats. In addition, three active pharmaceutical ingredients, which were approved in 2013 for use in human medicine and are of potential interest to veterinary medicine, are discussed. These are the antineoplastic ingredients dabrafenib, enzalutamide and vismodegib. PMID- 25119630 TI - Diagnostic efficacy of the leukogram and the chemiluminometric ACTH measurement to diagnose canine hypoadrenocorticism. AB - BACKGROUND AND OBJECTIVE: The gold standard in the diagnosis of canine hypoadrenocorticism (HA) is the adrenocorticotropin (ACTH) response test. As synthetic ACTH (tetracosactide [Synacthen(r)]) is currently not available in the European Union, the evaluation of other diagnostic tests seemed warranted. The diagnostic efficacy of electrolytes, the leukogram and endogenous ACTH concentrations to diagnose HA was investigated. MATERIAL AND METHODS: The medical records of 145 dogs with clinical signs suspect for spontaneous HA were included in a retrospective study. HA was diagnosed (n = 38) or ruled out (n = 84) by using an ACTH response test. In 23 patients HA was excluded by basal cortisol measurement. The diagnostic performance of various variables was assessed based on receiver operating characteristic (ROC) curves and by calculating differential positive rates. A decision tree (IBM SPSS Decision Trees 20, IBM Corporation) was constructed with the variables neutrophil to lymphocyte ratio (N/LR) and sodium to potassium ratio (Na/KR) to illustrate the diagnostic efficacy of the respective test results. RESULTS: The best single variables to diagnose HA were the endogenous ACTH concentration (area under the ROC curve [ROC AUC] 0.97; cutoff > 50 pmol/l: sensitivity 96%, specificity 100%) and the Na/KR (ROC AUC 0.905; cutoff <= 22: sensitivity 92%, specificity 91%). The diagnostic performance of various variables of the leukogram was poor to moderate (ROC AUC 0.625-0.828). 68% of dogs with HA had a Na/KR <= 22 and a N/LR <= 2.3, a combination not observed in dogs with non-adrenal diseases. CONCLUSION AND CLINICAL RELEVANCE: As secondary HA is very rare, endogenous ACTH measurement is a very good alternative to the traditional ACTH response test. Data also suggest that the combination of a Na/KR <= 22 and a N/LR <= 2.3 is highly specific and can be used to rule in HA. PMID- 25119633 TI - [Porencephaly in a female Greater Swiss Mountain Dog]. AB - A 15-month-old female Greater Swiss Mountain Dog was presented after an epileptic episode. In addition, the owner had noticed a recent marked change in the animal's behaviour. Because of the progressive nature of the neurological signs, a magnetic resonance imaging scan of the brain was performed and porencephaly in the parietal lobe of the right hemisphere was diagnosed. The dog was euthanized and submitted for pathology. Because of the histopathological findings and the history of a craniocerebral injury whilst a puppy, a traumatic genesis of this rare cystic lesion is discussed. PMID- 25119634 TI - [Ovarian tumor in a koi carp (Cyprinus carpio): Diagnosis, surgery, postoperative care and tumour classification]. AB - Although ovarian tumour in the koi (Cyprinus carpio) does not appear to be an uncommon condition, its occurrence and therapy has rarely been reported. In the present case, the decision for surgery was based on clinical and sonographic findings of an intracoelomic mass. We used tricaine methansulfonate for the anaesthesia. Laparotomy was performed by ventral access and an ovarian tumour of 12-cm diameter was removed. The wound was sutured in two layers using Vicryl(r). In addition to the application of an analgesic, an antibiotic and vitamins, the postoperative conditions the patient was kept under were adapted to support wound healing. The fish recovered uneventfully and was clinically healthy during the 16 month observation period. Based on the histological findings, the tumour was diagnosed as a thecoma. Investigations using antibodies against vimentin, cytokeratin, S 100 and glial fibrillary acidic protein (GFAP) failed to provide reliable results. PMID- 25119635 TI - [Evidence-based guidelines for cardio-pulmonary resuscitation in the dog and cat]. AB - Early recognition of a cardio-pulmonary arrest (CPA) is crucial for patient survival. Every non-breathing and non-responsive patient should be considered to have CPA, and examination of the vital signs should last no longer than 5-10 seconds. If in doubt, effective chest compressions should be started immediately (frequency of 100-120 compressions per minute, compression depth one third to half of the chest diameter, full chest wall recoil between the compressions, no interruption, change of compressing person every 2 minutes). Furthermore, the patient should be intubated and ventilated as early as possible with a frequency of 10 breaths per minute and a volume of 10 ml/kg. Additional measures include monitoring (electrocardiogram, end-expiratory carbon dioxide concentration), placement of an intravenous or intraosseous catheter, administration of opioid-, benzodiazepine- and/or alpha2-antagonists and ECG-dependent therapy to restore spontaneous circulation. In the case of asystole and pulseless electric activity, epinephrine (0.01 mg/kg every 3-5 minutes, alternative dose concept: 0.1 mg/kg epinephrine) is advised. In the case of CPA due to elevated vagal tonus or bradycardia, atropine should be given (0.04 mg/kg every 3-5 minutes). If ventricular fibrillation or pulseless ventricular tachyarrhythmia is present, defibrillation is the therapy of choice. When this is not possible, amiodarone (5 mg/kg) or lidocaine (2 mg/kg) should be administered. Furthermore, 100% oxygen should be given during resuscitation, while only a few patients benefit from infusion therapy. Following the return of spontaneous circulation, intensive care of the patient is necessary. This involves intense monitoring and support of the haemodynamic situation using intravenous fluids, vasopressors and positive inotropic drugs as well as an improvement of gas exchange and neuroprotection. PMID- 25119636 TI - Fluorescence in situ hybridization of chromosome 17 polysomy in breast cancer using thin tissue sections causes the loss of CEP17 and HER2 signals. AB - Human epidermal growth factor receptor 2 (HER2 gene) and chromosome 17 polysomy are associated with breast cancer prognosis, chemotherapy and hormone therapy. HER2 gene analysis using fluorescence in situ hybridization (FISH) with 4-um sections assuming a nuclear diameter of 6 um caused the loss of genetic DNA. Using intact whole nuclei FISH (WNFISH) and thin tissue section FISH (TTFISH), 109 cases of invasive breast cancer were examined to observe correlations among HER2 gene amplification, CEP17 polysomy and the HER2/CEP17 ratio. The results showed significant differences in the mean copy number of HER2 and the HER2/CEP17 ratios between the WNFISH and TTFISH groups. No significant differences were observed in HER2 amplified, equivocal and non-amplified HER2 samples. Thirty seven cases of CEP17 polysomy and 72 cases of non-polysomy were detected by WNFISH. Twenty-nine cases of CEP17 polysomy and 72 cases of non-polysomy were detected by TTFISH. Significant differences were observed between the two methods using the McNemar test (P=0.039). In conclusion, detection of chromosome 17 polysomy in breast cancer with fluorescence in situ hybridization using thin tissue sections may cause the loss of CEP17 and HER2 signals. PMID- 25119637 TI - Neuroprogression and staging in psychiatry: historical considerations. PMID- 25119638 TI - Looking beyond the prevalence of depression in Brazil: are we prepared to go further? PMID- 25119639 TI - Prevalence of depression morbidity among Brazilian adults: a systematic review and meta-analysis. AB - OBJECTIVE: To estimate the prevalence of depressive symptoms and major depressive disorder, as assessed in population-based cross-sectional studies of Brazilian adults. METHODS: We performed a systematic review of the literature. The major databases were searched up through October 2013. Two researchers selected the studies, extracted the data, and assessed their methodological quality. Meta analyses were performed using random effects. RESULTS: Of the 2,971 records retrieved, we selected 27 studies that assessed the prevalence of depression morbidity in 464,734 individuals (66% women). Eleven different screening tools were used to assess depression morbidity. The prevalence of depressive symptoms was 14% (95% confidence interval [95%CI] 13-16; I2 = 99.5%), whereas the 1-year prevalence of major depressive disorder was 8% (95%CI 7-10; I2 = 86.7%), and the lifetime prevalence of major depressive disorder was 17% (95%CI 14-19; I2 = 91.6%). All rates were higher in women than in men. No causes of heterogeneity could be identified. CONCLUSION: Depression morbidity was common among Brazilian adults, and affects more women than men. Inconsistencies across studies highlight the need for standardization of future research. Clinicians should routinely investigate for the presence of depression morbidity in this population. PMID- 25119640 TI - Will the DSM-5 changes in criteria for premenstrual dysphoric disorder impact clinical practice? PMID- 25119641 TI - Obsessive-compulsive disorder in fathers during pregnancy and postpartum. PMID- 25119642 TI - Developmental disability in schoolchildren from four Brazilian regions. PMID- 25119643 TI - Mental health of refugees: report of a successful case in Brazil. PMID- 25119645 TI - Direct observation of OH formation from stabilised Criegee intermediates. AB - The syn-CH3CHOO Criegee intermediate formed from the ozonolysis of propene and (E)-2-butene was detected via unimolecular decomposition and subsequent detection of OH radicals by a LIF-FAGE instrument. An observed time dependent OH concentration profile was analysed using a detailed model focusing on the speciated chemistry of Criegee intermediates based on the recent literature. The absolute OH concentration was found to depend on the steady state concentration of syn-CH3CHOO at the injection point while the time dependence of the OH concentration profile was influenced by the sum of the rates of unimolecular decomposition of syn-CH3CHOO and wall loss. By varying the most relevant parameters influencing the SCI chemistry in the model and based on the temporal OH concentration profile, the unimolecular decomposition rate k (293 K) of syn CH3CHOO was shown to lie within the range 3-30 s(-1), where a value of 20 +/- 10 s(-1) yields the best agreement with the CI chemistry literature. PMID- 25119644 TI - Stem cell characteristics of dormant cells and cisplatin-induced effects on the stemness of epithelial ovarian cancer cells. AB - Tumor dormancy is a common biological property of malignancies and a leading factor in treatment failure, metastasis and tumor recurrence. The present study generated mouse xenograft models by injection of PKH26-labeled SKOV3 ovarian cancer cells, which were divided into two groups: The control group (SKOV3-P tumors,) and the treatment group that generated resistant tumors following prolonged administration of cisplatin (SKOV3-R tumors). Administration of cisplatin resulted in inhibition of the tumor growth and SKOV3-R tumors coexisted with their host at a stable size. According to fluorochrome PKH26 retention, there were multiple cell clones (PKH26hi, PKH26low and PKH26neg cells) in the single cell line generated from xenograft tumors. PKH26hi subsets in SKOV3-P and SKOV3-R tumors were dormant cells, as the majority were arrested in G0/G1 phase and expressed high levels of the stem cell markers Oct-4, Nestin, CD117 and CD44. PKH26hi subsets also demonstrated greater clonogenic capability in vitro and tumorigenicity in vivo, as compared with PKH26low and PKH26neg cells. Notably, chemotherapy was demonstrated to lead to the enrichment and enhanced stem-like characteristics of dormant/slow-cycling PKH26hi cells. The results of the present study have demonstrated for the first time, to the best of our knowledge, that dormant tumor cells exhibit stem-like characteristics, and that cisplatin enhances these characteristics in epithelial ovarian cancer cells. PMID- 25119646 TI - A novel zinc-finger HIT protein with an additional PAPA-1-like region from Suaeda liaotungensis K. enhanced transgenic Arabidopsis drought and salt stresses tolerance. AB - Zinc-finger HIT belongs to the cross-brace zinc finger protein family and is involved in the regulation of plant defense and stress responses. In this study, we cloned a full-length zinc-finger HIT gene (1,377 bp) named SlPAPA1 using polymerase chain reaction from Suaeda liaotungensis K. and investigated its function by overexpression in transgenic Arabidopsis. SlPAPA1 contains a zinc finger HIT domain and a Pim-1-associated protein-1 (PAP-1)-associated protein-1 like (PAPA-1-like) conserved region. Its expression in S. liaotungensis was induced by drought, high-salt, and cold (4 degrees C) stresses and by abscisic acid (ABA). Subcellular localization experiments in onion epidermal cells indicated that SlPAPA1 is localized in the nucleus. Yeast-one hybrid assays showed that SlPAPA1 functions as a transcriptional activator. SlPAPA1 transgenic Arabidopsis displayed a higher survival ratio and lower rate of water loss under drought stress; a higher germination ratio, higher survival ratio, and lower root inhibition rate under salt stress; and a lower germination ratio and root inhibition rate under ABA treatment, compared with wild-type Arabidopsis. These results suggested that SlPAPA1 functions as a stress-responsive zinc-finger HIT protein involved in the ABA-dependent signaling pathway and may have potential applications in transgenic breeding to enhance crops abiotic stress tolerances. PMID- 25119647 TI - Virus-like particles from Escherichia Coli-derived untagged papaya ringspot virus capsid protein purified by immobilized metal affinity chromatography enhance the antibody response against a soluble antigen. AB - There is a growing interest in using virus-like particles (VLPs) as scaffolds for the presentation of antigens of choice to the immune system. In this work, VLPs from papaya ringspot virus capsid protein expressed in Escherichia coli were evaluated as enhancers of antibody response against a soluble antigen. Interestingly, although the capsid protein lacks a histidine tag, its purification by immobilized metal affinity chromatography was achieved. The formation of VLPs was demonstrated by electron microscopy for the first time for this capsid protein. VLPs were enriched by polyethylene glycol precipitation. Additionally, these VLPs were chemically coupled to green fluorescent protein in order to evaluate them as antigen carriers; however, bioconjugate instability was observed. Nonetheless, the adjuvant effect of these VLPs on BALB/c mice was evaluated, using GFP as antigen, resulting in a significant increase in anti-GFP IgG response, particularly, IgG1 class, demonstrating that the VLPs enhance the immune response against the antigen chosen in this study. PMID- 25119649 TI - Approaches to the total synthesis of chaetochalasin A. AB - Chaetochalasin A is a complex natural product whose biosynthesis may involve two domino Diels-Alder reactions. Approaches to the total synthesis of chaetochalasin A using this approach have been studied. Methyl (6R,8S,2Z,4E,10E,12E,14E) 6,8,10,14-tetramethylhexadeca-2,4,10,12,14-pentaenoate was identified as a key intermediate and was synthesized from (E)-1-bromo-4-tert-butyldimethylsilyloxy-2 methylbut-2-ene using diastereoselective alkylations of derivatives of (+) pseudoephedrine to introduce the stereogenic centres, a modified Julia reaction to prepare the conjugated triene and a phosphonate condensation to provide the (2Z)-alkene. However, during the synthesis, facile geometrical isomerisation of the (14E)-trisubstituted and (2Z)-double-bonds was observed and attempts to incorporate this pentaene into a synthesis of chaetochalasin A led to the formation of mixtures of products. The analogous ethyl 6,8,10,14 tetramethylhexadeca-4,10,12,14-tetraenoate [that lacks the (2Z)-double-bond] was incorporated into a Diels-Alder precursor by acylation of a valine-derived N acylpyrrolidinone followed by oxidative elimination of the corresponding 3 (phenylselanyl)pyrrolidinone. However, preliminary studies of the macrocycle forming Diels-Alder reaction for a synthesis of chaetochalasin A were complicated by (E,Z)-isomerisation of the (10E)-double-bond of the conjugated triene and three Diels-Alder adducts were isolated and characterised. Further studies of this approach to chaetochalasin A will require an alternative procedure for the generation of the acylpyrrolinone in the presence of the acid sensitive conjugated triene. PMID- 25119648 TI - Matrix-assisted refolding, purification and activity assessment using a 'form invariant' assay for matrix metalloproteinase 2 (MMP2). AB - Matrix metalloproteinases expression is used as biomarker for various cancers and associated malignancies. Since these proteinases can cleave many intracellular proteins, overexpression tends to be toxic; hence, a challenge to purify them. To overcome these limitations, we designed a protocol where full length pro-MMP2 enzyme was overexpressed in E. coli as inclusion bodies and purified using 6xHis affinity chromatography under denaturing conditions. In one step, the enzyme was purified and refolded directly on the affinity matrix under redox conditions to obtain a bioactive protein. The pro-MMP2 protein was characterized by mass spectrometry, CD spectroscopy, zymography and activity analysis using a simple in house developed 'form invariant' assay, which reports the total MMP2 activity independent of its various forms. The methodology yielded higher yields of bioactive protein compared to other strategies reported till date, and we anticipate that using the protocol, other toxic proteins can also be overexpressed and purified from E. coli and subsequently refolded into active form using a one step renaturation protocol. PMID- 25119650 TI - Kinetics of 3-nitrotyrosine modification on exposure to hypochlorous acid. AB - The markers 3-nitrotyrosine and 3-chlorotyrosine are measured as surrogates for reactive nitrogen species and hypochlorous acid respectively, which are both elevated in inflamed human tissues. Previous studies reported a loss of 3 nitrotyrosine when exposed to hypochlorous acid, suggesting that observations of 3-nitrotyrosine underestimate the presence of reactive nitrogen species in diseased tissue (Whiteman and Halliwell, Biochemical and Biophysical Research Communications, 258, 168-172 (1999)). This report evaluates the significance of 3 nitrotyrosine loss by measuring the kinetics of the reaction between 3 nitrotyrosine and hypochlorous acid. The results demonstrate that 3-nitrotyrosine is chlorinated by hypochlorous acid or chloramines to form 3-chloro-5 nitrotyrosine. As 3-nitrotyrosine from in vivo samples is usually found within proteins rather than as free amino acid, we also examined the reaction of 3 nitrotyrosine modification in the context of peptides. The chlorination of 3 nitrotyrosine in peptides was observed to occur up to 700-fold faster than control reactions using equivalent amino acid mixtures. These results further advance our understanding of tyrosine chlorination and the use of 3-nitrotyrosine formed in vivo as a biomarker of reactive nitrogen species. PMID- 25119651 TI - miR-195/497 induce postnatal quiescence of skeletal muscle stem cells. AB - Skeletal muscle stem cells (MuSCs), the major source for skeletal muscle regeneration in vertebrates, are in a state of cell cycle arrest in adult skeletal muscles. Prior evidence suggests that embryonic muscle progenitors proliferate and differentiate to form myofibres and also self-renew, implying that MuSCs, derived from these cells, acquire quiescence later during development. Depletion of Dicer in adult MuSCs promoted their exit from quiescence, suggesting microRNAs are involved in the maintenance of quiescence. Here we identified miR-195 and miR-497 that induce cell cycle arrest by targeting cell cycle genes, Cdc25 and Ccnd. Reduced expression of MyoD in juvenile MuSCs, as a result of overexpressed miR-195/497 or attenuated Cdc25/Ccnd, revealed an intimate link between quiescence and suppression of myogenesis in MuSCs. Transplantation of cultured MuSCs treated with miR-195/497 contributed more efficiently to regenerating muscles of dystrophin-deficient mice, indicating the potential utility of miR-195/497 for stem cell therapies. PMID- 25119652 TI - Factors Affecting Caregiver Burden 1 Year After Severe Traumatic Brain Injury: A Prospective Nationwide Multicenter Study. AB - OBJECTIVES: To assess burden in the caregivers of patients with severe traumatic brain injury (TBI) 1 year postinjury, related to caregiver's demographic data and social network, patient's demographic data, injury severity, and functional status. DESIGN: Prospective national multicenter study. Self-report from caregivers, patient data collected from the national cohort on patients with severe TBI. PARTICIPANTS: 92 caregivers. MAIN OUTCOME MEASURE: The Caregiver Burden Scale (CBS). RESULTS: Total caregiver burden was reported high in 16% of caregivers and moderate in 34%. The mean total burden index was 2.12, indicating a moderate burden. Caregivers reported highest scores on the General strain index, followed by the Disappointment index. Poor social network, feeling loneliness, and caring for patients with severe disability were significant predictors of higher burden in univariate analyses (P < .01). Multiple linear regression analyses showed that experiencing loneliness and caring for a patient with more severe disability were independent predictors for higher caregiver burden for all CBS indices. Marital status (married) and low frequency of meeting friends were significant results in some indices. CONCLUSIONS: Lack of a social network, feeling loneliness, and patient's functional status are predictors of caregiver burden. General strain, disappointment, and isolation were identified as areas in which caregiver burden is high. PMID- 25119653 TI - Trajectories of Sleep and Its Predictors in the First Year Following Traumatic Brain Injury. AB - OBJECTIVES: To examine how sleep patterns change over the first year following traumatic brain injury (TBI) and to determine whether specific demographic and disease characteristics predict the trajectories of sleep. DESIGN: Prospective study. PARTICIPANTS: Fifty-three patients with first-ever mild to severe TBI. MAIN MEASUREMENTS: Sleep measured by actigraphy for 7 consecutive days in the first, third, sixth, and twelfth months following TBI: Chinese versions of Beck Anxiety Inventory and Beck Depression Inventory-II (CBDI-II) measured at the same time points. Data were analyzed with a linear mixed model. RESULTS: Sleep efficiency (the ratio of sleep time to the total time spent in bed) showed a significant upward trend during the study period. Scores on the Chinese version of the Beck Anxiety Inventory and the CBDI-II as well as the use of analgesics significantly predicted the slope of change in sleep efficiency over time. CONCLUSIONS: Poor sleep efficiency is a common symptom in the first year among patients with first-ever TBI. Healthcare providers should consider both mental health and pain issues when dealing with sleep complaints in patients with TBI. PMID- 25119655 TI - Preferential adsorption behavior of methylene blue dye onto surface hydroxyl group enriched TiO2 nanotube and its photocatalytic regeneration. AB - The present manuscript focus on the synthesis of surface hydroxyl group enriched titanium dioxide nanotube (TNT) by hydrothermal method for preferential adsorption of methylene blue (MB) dye. The mixture of methylene blue (MB) and rhodamine B (RhB) dye was used to study the preferential adsorption nature of TNT. The synthesized TNT were characterized by various techniques such as powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption, and ammonia-temperature programmed desorption (NH3-TPD) analysis. Result demonstrated that enhancement in the surface area of TNT and higher number of hydroxyl group on the surface of TNT. In the binary mixture, the adsorption of MB dye was 12.9 times higher as compared to RhB dye, which clearly indicated the preferential adsorption of MB dye on TNT surface. The preferential interaction of MB on TNT is due to the electrostatic interaction between the cationic MB and negatively charged TNT surface. The preferential adsorption of MB dye was studied by applying Langmuir, Freundlich and Sips isotherm; pseudo-first and second-order kinetic model. Furthermore, the regeneration of dye adsorbed TNT was carried out by eco-friendly photocatalytic process under the irradiation of ultraviolet light. PMID- 25119654 TI - Association of alcohol drinking with verbal and visuospatial memory impairment in older adults: Clinical Research Center for Dementia of South Korea (CREDOS) study. AB - BACKGROUND: The study's aim was to examine the association of alcohol consumption with verbal and visuospatial memory impairment in older people. METHODS: Participants were 1,572, aged >=60 years, in the hospital-based registry of the Clinical Research Center for Dementia of South Korea (CREDOS). Moderate drinking was defined as no more than seven drinks per week and three drinks per day. Memory impairment was defined as performance with more than 1 standard deviation below the mean value on the Seoul Verbal Learning Test and Rey Complex Figure Test. RESULTS: Those who consumed alcohol moderately, compared with abstainers, had a lower odds of verbal memory impairment (Odds Ratio [OR] = 0.64; 95% Confidence Interval [CI]: 0.46-0.87), adjusting for covariates. Visuospatial memory, however, was not significantly associated with alcohol consumption. CONCLUSIONS: Moderate alcohol drinking is associated with a reduced likelihood of verbal memory impairment among older people attending memory clinics. PMID- 25119657 TI - Contact electrification field-effect transistor. AB - Utilizing the coupled metal oxide semiconductor field-effect transistor and triboelectric nanogenerator, we demonstrate an external force triggered/controlled contact electrification field-effect transistor (CE-FET), in which an electrostatic potential across the gate and source is created by a vertical contact electrification between the gate material and a "foreign" object, and the carrier transport between drain and source can be tuned/controlled by the contact-induced electrostatic potential instead of the traditional gate voltage. With the two contacted frictional layers vertically separated by 80 MUm, the drain current is decreased from 13.4 to 1.9 MUA in depletion mode and increased from 2.4 to 12.1 MUA in enhancement mode at a drain voltage of 5 V. Compared with the piezotronic devices that are controlled by the strain-induced piezoelectric polarization charged at an interface/junction, the CE-FET has greatly expanded the sensing range and choices of materials in conjunction with semiconductors. The CE-FET is likely to have important applications in sensors, human-silicon technology interfacing, MEMS, nanorobotics, and active flexible electronics. Based on the basic principle of the CE-FET, a field of tribotronics is proposed for devices fabricated using the electrostatic potential created by triboelectrification as a "gate" voltage to tune/control charge carrier transport in conventional semiconductor devices. By the three-way coupling among triboelectricity, semiconductor, and photoexcitation, plenty of potentially important research fields are expected to be explored in the near future. PMID- 25119656 TI - Postoperative radioactive iodine administration for differentiated thyroid cancer patients. AB - PURPOSE OF REVIEW: Radioactive iodine (RAI) is administered postoperatively to the majority of thyroid cancer patients. No available study has demonstrated any benefit in low-risk patients. RECENT FINDINGS: RAI should be used selectively in low and intermediate-risk patients, based on the surgical and pathological reports and on postoperative serum thyroglobulin level and neck ultrasonography. When used, a low activity (30 mCi) is administered following recombinant human thyrotropin stimulation. High-risk patients are treated with a high activity of RAI (100 mCi or more). SUMMARY: RAI is not administered in many low-risk patients who can be reliably followed up with serum thyroglobulin determination on L thyroxine treatment and neck ultrasonography. RAI may be administered in case of abnormality, and this delay will not reduce the chance of cure. PMID- 25119658 TI - Dynamics of the DNA repair proteins WRN and BLM in the nucleoplasm and nucleoli. AB - We have investigated the mobility of two EGFP-tagged DNA repair proteins, WRN and BLM. In particular, we focused on the dynamics in two locations, the nucleoli and the nucleoplasm. We found that both WRN and BLM use a "DNA-scanning" mechanism, with rapid binding-unbinding to DNA resulting in effective diffusion. In the nucleoplasm WRN and BLM have effective diffusion coefficients of 1.62 and 1.34 MUm(2)/s, respectively. Likewise, the dynamics in the nucleoli are also best described by effective diffusion, but with diffusion coefficients a factor of ten lower than in the nucleoplasm. From this large reduction in diffusion coefficient we were able to classify WRN and BLM as DNA damage scanners. In addition to WRN and BLM we also classified other DNA damage proteins and found they all fall into one of two categories. Either they are scanners, similar to WRN and BLM, with very low diffusion coefficients, suggesting a scanning mechanism, or they are almost freely diffusing, suggesting that they interact with DNA only after initiation of a DNA damage response. PMID- 25119661 TI - Applicability domain based on ensemble learning in classification and regression analyses. AB - We discuss applicability domains (ADs) based on ensemble learning in classification and regression analyses. In regression analysis, the AD can be appropriately set, although attention needs to be paid to the bias of the predicted values. However, because the AD set in classification analysis is too wide, we propose an AD based on ensemble learning and data density. First, we set a threshold for data density below which the prediction result of new data is not reliable. Then, only for new data with a data density higher than the threshold, we consider the reliability of the prediction result based on ensemble learning. By analyzing data from numerical simulations and quantitative structural relationships, we validate our discussion of ADs in classification and regression analyses and confirm that appropriate ADs can be set using the proposed method. PMID- 25119660 TI - MicroRNA-449 suppresses proliferation of hepatoma cell lines through blockade lipid metabolic pathway related to SIRT1. AB - MicroRNA (miRNA or miR) inhibition of oncogenic related pathways has been shown to be a promising therapeutic approach for cancer. SIRT1 might be a promoter factor on tumorigenesis of hepatocellular carcinoma (HCC). However, the mechanism is unknown. We investigated whether miRNAs regulate the SIRT1 and its downstream SREBP-lipogenesis-cholesterogenesis metabolic pathway in hepatoma cells. Human hepatoma cells were transfected with miR-449 mimics and inhibitors, and the effects of miR-449 on cell proliferation was assessed. We identified the miRNAs, miR-449, that control lipogenesis and cholesterogenesis in hepatoma cells by inhibiting SIRT1 and SREBP-1c expression and downregulating their targeted genes, including fatty acid synthase (FASN) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). MiR-449 repressed DNA synthesis, mitotic entry and proliferation of hepatoma cells. Restoration of miR-449 led to suppression of SIRT1 expression and liver tumorigenesis. The newly identified miRNAs, miR-449 represents a novel targeting mechanism for HCC therapy. PMID- 25119662 TI - Redox and photoinduced electron-transfer properties in short distance organoboryl ferrocene-subphthalocyanine dyads. AB - Reaction between ferrocene lithium or ethynylferrocene magnesium bromide and (chloro)boronsubphthalocyanine leads to formation of ferrocene- (2) and ethynylferrocene- (3) containing subphthalocyanine dyads with a direct organometallic B-C bond. New donor-acceptor dyads were characterized using UV-vis and magnetic circular dichroism (MCD) spectroscopies, NMR method, and X-ray crystallography. Redox potentials of the rigid donor-acceptor dyads 2 and 3 were studied using the cyclic voltammetry (CV) and differential pulse voltammetry (DPV) approaches and compared to the parent subphthalocyanine 1 and conformationally flexible subphthalocyanine ferrocenenylmethoxide (4) and ferrocenyl carboxylate (5) dyads reported earlier. It was found that the first oxidation process in dyads 2 and 3 is ferrocene-centered, while the first reduction as well as the second oxidation are centered at the subphthalocyanine ligand. Density functional theory-polarized continuum model (DFT-PCM) and time dependent (TD) DFT-PCM methods were used to probe the electronic structures and explain the UV-vis and MCD spectra of complexes 1-5. DFT-PCM calculations suggest that the LUMO, LUMO+1, and HOMO-3 in new dyads 2 and 3 are centered at the subphthalocyanine ligand, while the HOMO to HOMO-2 in both dyads are predominantly ferrocene-centered. TDDFT-PCM calculations on compounds 1-5 are indicative of the pi -> pi* transitions dominance in their UV-vis spectra, which is consistent with the experimental data. The excited state dynamics of the parent subphthalocyanine 1 and dyads 2-5 were investigated using time-resolved transient spectroscopy. In the dyads 2-5, the initially excited state is rapidly (<2 ps) quenched by electron transfer from the ferrocene ligand. The lifetime of the charge transfer state demonstrates a systematic dependence on the structure of the bridge between the subphthalocyanine and ferrocene. PMID- 25119659 TI - Systemic administration of erythropoietin inhibits retinopathy in RCS rats. AB - OBJECTIVE: Royal College of Surgeons (RCS) rats develop vasculopathy as photoreceptors degenerate. The aim of this study was to examine the effect of erythropoietin (EPO) on retinopathy in RCS rats. METHODS: Fluorescein angiography was used to monitor retinal vascular changes over time. Changes in retinal glia and vasculature were studied by immunostaining. To study the effects of EPO on retinal pathology, EPO (5000 IU/kg) was injected intraperitoneally in 14 week old normal and RCS rats twice a week for 4 weeks. Changes in the retinal vasculature, glia and microglia, photoreceptor apoptosis, differential expression of p75 neurotrophin receptor (p75NTR), pro-neurotrophin 3 (pro-NT3), tumour necrosis factor-alpha (TNFalpha), pigment epithelium derived factor (PEDF) and vascular endothelial growth factor-A (VEGF-A), the production of CD34(+) cells and mobilization of CD34(+)/VEGF-R2(+) cells as well as recruitment of CD34(+) cells into the retina were examined after EPO treatment. RESULTS: RCS rats developed progressive capillary dropout and subretinal neovascularization which were accompanied by retinal gliosis. Systemic administration of EPO stabilized the retinal vasculature and inhibited the development of focal vascular lesions. Further studies showed that EPO modulated retinal gliosis, attenuated photoreceptor apoptosis and p75NTR and pro-NT3 upregulation, promoted the infiltration of ramified microglia and stimulated VEGF-A expression but had little effect on TNFalpha and PEDF expression. EPO stimulated the production of red and white blood cells and CD34(+) cells along with effective mobilization of CD34(+)/VEGF-R2(+) cells. Immunofluorescence study demonstrated that EPO enhanced the recruitment of CD34+ cells into the retina. CONCLUSIONS: Our results suggest that EPO has therapeutic potentials in treatment of neuronal and vascular pathology in retinal disease. The protective effects of EPO on photoreceptors and the retinal vasculature may involve multiple mechanisms including regulation of retinal glia and microglia, inhibition of p75NTR-pro-NT3 signaling together with stimulation of production and mobilization of bone marrow derived cells. PMID- 25119663 TI - Substrate positioning by Gln(239) stimulates turnover in factor inhibiting HIF, an alphaKG-dependent hydroxylase. AB - Nonheme Fe(II)/alphaKG-dependent oxygenases catalyze diverse reactions, typically inserting an O atom from O2 into a C-H bond. Although the key to their catalytic cycle is the fact that binding and positioning of primary substrate precede O2 activation, the means by which substrate binding stimulates turnover is not well understood. Factor Inhibiting HIF (FIH) is a Fe(II)/alphaKG-dependent oxygenase that acts as a cellular oxygen sensor in humans by hydroxylating the target residue Asn(803), found in the C-terminal transactivation domain (CTAD) of hypoxia inducible factor-1. FIH-Gln(239) makes two hydrogen bonds with CTAD Asn(803), positioning this target residue over the Fe(II). We hypothesized the positioning of the side chain of CTAD-Asn(803) by FIH-Gln(239) was critical for stimulating O2 activation and subsequent substrate hydroxylation. The steady state characterization of five FIH-Gln(239) variants (Ala, Asn, Glu, His, and Leu) tested the role of hydrogen bonding potential and sterics near the target residue. Each variant exhibited a 20-1200-fold decrease in kcat and kcat/KM(CTAD), but no change in KM(CTAD), indicating that the step after CTAD binding was affected by point mutation. Uncoupled O2 activation was prominent in these variants, as shown by large coupling ratios (C = [succinate]/[CTAD-OH] = 3 5) for each of the FIH-Gln(239) -> X variants. The coupling ratios decreased in D2O, indicating an isotope-sensitive inactivation for variants, not observed in the wild type. The data presented indicate that the proper positioning of CTAD Asn(803) by FIH-Gln(239) is necessary to suppress uncoupled turnover and to support substrate hydroxylation, suggesting substrate positioning may be crucial for directing O2 reactivity within the broader class of alphaKG hydroxylases. PMID- 25119667 TI - A high-protein formula increases colonic peptide transporter 1 activity during neonatal life in low-birth-weight piglets and disturbs barrier function later in life. AB - Dietary peptides are absorbed along the intestine through peptide transporter 1 (PepT-1) which is highly responsive to dietary protein level. PepT-1 is also involved in gut homeostasis, both initiating and resolving inflammation. Low birth-weight (LBW) neonates are routinely fed a high-protein (HP) formula to enhance growth. However, the influence of this nutritional practice on PepT-1 activity is unknown. Intestinal PepT-1 activity was compared in normal-birth weight (NBW) and LBW piglets. The effect of HP v. normal-protein (NP) formula feeding on PepT-1 activity and gut homeostasis in LBW piglets was evaluated, during the neonatal period and in adulthood. Flux of cephalexin (CFX) across the tissue mounted in Ussing chambers was used as an indicator of PepT-1 activity. CFX flux was greater in the ileum, but not jejunum or colon, of LBW than NBW piglets during the neonatal period. When LBW piglets were formula-fed, the HP formula increased colonic CFX during the 1st week of life. Later in life, intestinal CFX fluxes and barrier function were similar whether LBW pigs had been fed NP or HP formula. However, colonic permeability of HP- but not NP-fed pigs increased when luminal pH was brought to 6.0. The formyl peptide N-formyl methionyl-leucyl-phenylalanine conferred colonic barrier protection in HP-fed piglets. Heat shock protein 27 levels in the colonic mucosa of HP-fed LBW pigs correlated with the magnitude of response to the acidic challenge. In conclusion, feeding a HP formula enhanced colonic PepT-1 activity in LBW pig neonates and increased sensitivity of the colon to luminal stress in adulthood. PMID- 25119668 TI - Micro-segmented flow and multisensor-technology for microbial activity profiling. AB - The combination of micro-segmented flow with miniaturized flow-through multisensor-technology has been utilized for metabolite profiling of soil bacteria. Series of sub-MUl segments were generated containing soil sample slurry from historic copper mining sites and exposed to heavy metal salts of copper and nickel. Segments were examined for bacterial growth and spectral properties as well as for the effect of heavy metal-treatment after different incubation times. In order to evaluate microbial growth, extinction was recorded with 4 different spectral channels. Fluorescence was measured using a microflow-through fluorometer to detect both growth and production of fluorescent dyes or metabolites. The incidence of single segments with enhanced absorption in one of the spectral channels or enhanced fluorescence was scored to detect soil microorganisms with interesting properties for further screening. The study could show that the number of vegetated segments, the density of microorganisms in the segments after cultivation and the spectral response are different for separate soil samples and different metals. Thus, the highly parallelized and miniaturized segmented flow method is a promising tool for profiling of soil samples with regard to identifying micro-organisms with interesting profiles for secondary metabolite-production. PMID- 25119665 TI - Multi-level factors affecting entry into and engagement in the HIV continuum of care in Iringa, Tanzania. AB - Progression through the HIV continuum of care, from HIV testing to lifelong retention in antiretroviral therapy (ART) care and treatment programs, is critical to the success of HIV treatment and prevention efforts. However, significant losses occur at each stage of the continuum and little is known about contextual factors contributing to disengagement at these stages. This study sought to explore multi-level barriers and facilitators influencing entry into and engagement in the continuum of care in Iringa, Tanzania. We used a mixed methods study design including facility-based assessments and interviews with providers and clients of HIV testing and treatment services; interviews, focus group discussions and observations with community-based providers and clients of HIV care and support services; and longitudinal interviews with men and women living with HIV to understand their trajectories in care. Data were analyzed using narrative analysis to identify key themes across levels and stages in the continuum of care. Participants identified multiple compounding barriers to progression through the continuum of care at the individual, facility, community and structural levels. Key barriers included the reluctance to engage in HIV services while healthy, rigid clinic policies, disrespectful treatment from service providers, stock-outs of supplies, stigma and discrimination, alternate healing systems, distance to health facilities and poverty. Social support from family, friends or support groups, home-based care providers, income generating opportunities and community mobilization activities facilitated engagement throughout the HIV continuum. Findings highlight the complex, multi-dimensional dynamics that individuals experience throughout the continuum of care and underscore the importance of a holistic and multi-level perspective to understand this process. Addressing barriers at each level is important to promoting increased engagement throughout the continuum. PMID- 25119664 TI - Membrane interacting regions of Dengue virus NS2A protein. AB - The Dengue virus (DENV) NS2A protein, essential for viral replication, is a poorly characterized membrane protein. NS2A displays both protein/protein and membrane/protein interactions, yet neither its functions in the viral cycle nor its active regions are known with certainty. To highlight the different membrane active regions of NS2A, we characterized the effects of peptides derived from a peptide library encompassing this protein's full length on different membranes by measuring their membrane leakage induction and modulation of lipid phase behavior. Following this initial screening, one region, peptide dens25, had interesting effects on membranes; therefore, we sought to thoroughly characterize this region's interaction with membranes. This peptide presents an interfacial/hydrophobic pattern characteristic of a membrane-proximal segment. We show that dens25 strongly interacts with membranes that contain a large proportion of lipid molecules with a formal negative charge, and that this effect has a major electrostatic contribution. Considering its membrane modulating capabilities, this region might be involved in membrane rearrangements and thus be important for the viral cycle. PMID- 25119669 TI - High seroprevalence of human herpesvirus type 8 infection in males with advanced lung carcinoma. AB - Human herpesvirus type 8 (HHV-8) DNA is consistently found in all types of Kaposi's sarcoma, which is prevalent in immunocompromised patients. Patients with advanced lung carcinoma often showed immunologic abnormalities, and prevalence of HHV-8 infection is unclear. In this study, blood samples from 109 lung carcinoma patients and 109 age- and sex-matched healthy controls were analyzed for lymphocyte and monocyte counts, and for antibody, DNA, and genotype of HHV-8. Lung carcinoma patients had significantly lower lymphocyte and higher monocyte counts than healthy controls (p < 0.0001, both). HHV-8 seropositivity was more prevalent in lung carcinoma patients (41.3%), particularly in male patients (50.8%), than in controls (24.8%) (p = 0.01 and 0.002, respectively). The seropositivity was also significantly higher in male (50.8%) than female patients (27.3%, p = 0.01). Titers of HHV-8 antibody in patients also significantly exceeded those in controls (p = 0.004). Under a higher threshold (antibody titer >=1:160) which is equivalent to that of enzyme-linked immunosorbent assay, lung carcinoma patients still had higher HHV-8 seropositivity than controls (p = 0.006). Three patients with stage IV lung carcinoma were positive for HHV-8 DNA with K1 gene subtype C3, D1, and E, respectively; they had much lower lymphocyte counts (658 +/- 132 uL) than patients positive for HHV-8 antibodies only (1,449 +/- 873 uL). The study indicates that lung carcinoma patients, particularly males, have a high seroprevalence of HHV-8. HHV-8 DNA detected in the patients with advanced lung carcinoma may be a result of virus reactivation in the immunocompromised status. PMID- 25119671 TI - The Au(I) catalyzed activation of allenamides and their subsequent transformation into chromanes: a method for the regiocontrolled addition to the alpha- and gamma positions of the allene unit. AB - Au(I) activation of allenamides in the presence of phenols leads to the formation of chromanes in moderate to good yields. This catalytic process is dependent on the counterion which facilitates the activation of the in situ formed imine. Furthermore, this iminium can be intercepted by trimethylallyl silane, via the Hosomi-Sakurai reaction, giving a formal procedure for the regioselective intermolecular addition of two carbon nucleophiles to an allenamide at the alpha- and gamma-positions. PMID- 25119670 TI - Vaccination with Streptococcus pyogenes nuclease A stimulates a high antibody response but no protective immunity in a mouse model of infection. AB - Streptococcus pyogenes is a human pathogen which causes a spectrum of diseases ranging from pharyngitis to rheumatic fever, necrotising fasciitis and toxic shock syndrome. Development of a vaccine for S. pyogenes has been confounded both by the diversity of the disease-causing serotypes and the spectre of inadvertently stimulating autoimmunity. The S. pyogenes nuclease A (SpnA) is a recently characterised virulence factor that is highly conserved across strains and expressed during human disease. Deletion of spnA from S. pyogenes results in reduced survival of bacteria in whole human blood and attenuated virulence in a mouse model of infection. Collectively these features suggest that SpnA has potential as a vaccine candidate for S. pyogenes. Mice vaccinated subcutaneously with single or multiple doses of recombinant SpnA emulsified in Incomplete Freund's Adjuvant developed a robust and durable IgG response, including neutralising activity, to this protein. However, vaccination with rSpnA conferred no advantage in terms of lesion development, disease symptoms or colonisation levels after a sub-lethal subcutaneous challenge with S. pyogenes. Anti-SpnA serum IgG responses and neutralising activity were increased in response to challenge, indicating that SpnA is expressed in vivo. SpnA is unlikely to be a suitable antigen for a vaccine against S. pyogenes. PMID- 25119672 TI - Roles of Ebp2 and ribosomal protein L36 in ribosome biogenesis in Saccharomyces cerevisiae. AB - Ebp2 plays an essential role in biogenesis of 60S ribosomal subunits. We determined the genetic interactions between EBP2 and RPL36A/B, which encodes ribosomal protein L36a/b. RPL36A/B was a multicopy suppressor to ebp2 mutants, and the suppression was not common to defects in ribosome biogenesis resulting from other mutations of assembly factors. Disruption of RPL36A or RPL36B caused synthetic enhancement of the growth defect of the ebp2-14 allele at high temperatures. Disruption of RPL36B led to a more severe growth defect than that of RPL36A due to imbalances in the expression levels of the duplicated genes. Primer-extension analysis revealed that L36a/b is required for the processing of 27SA2, 27SA3, and 27SBL pre-rRNAs. Two-hybrid analysis indicated that Ebp2 interacts with ribosomal proteins L36a/b, L34a/b, and L8, which in mature ribosomes are located adjacent to each other in close proximity to the 3' end of 5.8S rRNA. These results suggest that Ebp2 functions cooperatively with ribosomal proteins L36, L34, and L8 in biogenesis of the 60S ribosomal subunit. PMID- 25119674 TI - Rapid development of proteomics in China: from the perspective of the Human Liver Proteome Project and technology development. AB - Proteomics focuses on the systematic identification and quantification of entire proteomes and interpretation of proteins' biological functions. During the last decade, proteomics in China has grown much faster than other research fields in the life sciences. At the beginning of the second decade of the 21(st) century, the rapid development of high-resolution and high-speed mass spectrometry makes proteomics a powerful tool to study the mechanisms underlying physiological/pathological processes in organisms. This article provides a brief overview of proteomics technology development and representative scientific progress of the Human Liver Proteome Project (HLPP) in China over the past three years. PMID- 25119673 TI - Tetracaine, a local anesthetic, preferentially induces translational inhibition with processing body formation rather than phosphorylation of eIF2alpha in yeast. AB - It is unclear whether local anesthetics, such as tetracaine, and antipsychotics, such as phenothiazines, act on lipids or proteins. In Saccharomyces cerevisiae, these drugs inhibit growth, translation initiation, and actin polarization, and induce cell lysis at high concentrations. These activities are likely due to the cationic amphiphilic structure common to these agents. Although drug-induced translational inhibition is conserved in mammalian cells, other mechanisms, including the phosphorylation of eIF2alpha, a eukaryotic translational initiation factor, remain poorly understood. At a concentration of 10 mM, tetracaine rapidly inhibited translation initiation and lysed cells, whereas, at 2.5 mM, it slowly induced inhibition without lysis. The pat1 disruptant defective in mRNA decapping and the xrn1 disruptant defective in 5'-3' exoribonuclease were partially resistant to translational inhibition by tetracaine at each concentration, but the gcn2 disruptant defective in the eIF2alpha kinase was not. Phosphorylation of eIF2alpha was induced by 10 mM but not by 2.5 mM tetracaine, whereas processing bodies (P-bodies) were formed at 2.5 mM in Pat1-dependent and -independent manners. Therefore, administration of tetracaine inhibits translation initiation with P-body formation at both concentrations but acts via the Gcn2-eIF2alpha system only at the higher concentration. Because other local anesthetics and phenothiazines induced Pat1-dependent P-body formation, the mechanisms involved in translational inhibition by these cationic amphiphiles are similar. These results suggest that this dose-dependent biphasic translational inhibition by tetracaine results from an increase in membrane proteins that are indirectly inhibited by nonspecific interactions of cationic amphiphiles with membrane lipids. PMID- 25119675 TI - Pathogenesis of a Chinese strain of bovine adenovirus type 3 infection in albino guinea pigs. AB - Bovine adenovirus type 3 (BAV-3) is considered one of the most important respiratory tract agents of cattle and is widespread among cattle around the world. A BAV-3 strain was isolated from a bovine nasal swab for the first time in China in 2009 and named HLJ0955. Subsequently, BAV-3 has frequently been isolated from calves with respiratory diseases in China. To date, only limited study on the pathogenesis of BAV-3 infection in cotton rats has been conducted, and the pathogenesis of BAV-3 infection in guinea pigs has not been reported. Therefore, sixteen albino guinea pigs were inoculated intranasally with HLJ0955. All of the infected guinea pigs had apparently elevated rectal temperatures (39.2 degrees C 39.9 degrees C) at 2-7 days post-inoculation (PI). Consolidation and petechial hemorrhage were also observed in guinea pigs experimentally infected with HLJ0955. Viral replication was detectable by virus isolation and titration and by immunohistochemistry in the lungs of guinea pigs as early as 24 h PI. Viral DNA was detectable in the lungs of infected guinea pigs during 11 days of observation by real-time PCR. Virus-neutralizing antibodies against BAV-3 were detectable from 11 days PI and reached a peak titer at 15 days PI. Histopathological changes mainly occurred in the lungs of infected guinea pigs and were characterized by thickening of alveolar septa, mononuclear cell infiltration, hemorrhage and alveolar epithelial necrosis. These results indicate that HLJ0955 can replicate in the lungs of guinea pigs and cause fever and gross and histological lesions. The guinea pig infection model of BAV-3 would serve as a useful system for monitoring the infection process and pathogenesis of the Chinese BAV-3 strain HLJ0955, as well as immune responses to BAV-3 vaccines. PMID- 25119676 TI - Improvements to pairwise sequence comparison (PASC): a genome-based web tool for virus classification. AB - The number of viral genome sequences in the public databases is increasing dramatically, and these sequences are playing an important role in virus classification. Pairwise sequence comparison is a sequence-based virus classification method. A program using this method calculates the pairwise identities of virus sequences within a virus family and displays their distribution, and visual analysis helps to determine demarcations at different taxonomic levels such as strain, species, genus and subfamily. Subsequent comparison of new sequences against existing ones allows viruses from which the new sequences were derived to be classified. Although this method cannot be used as the only criterion for virus classification in some cases, it is a quantitative method and has many advantages over conventional virus classification methods. It has been applied to several virus families, and there is an increasing interest in using this method for other virus families/groups. The Pairwise Sequence Comparison (PASC) classification tool was created at the National Center for Biotechnology Information. The tool's database stores pairwise identities for complete genomes/segments of 56 virus families/groups. Data in the system are updated every day to reflect changes in virus taxonomy and additions of new virus sequences to the public database. The web interface of the tool ( http://www.ncbi.nlm.nih.gov/sutils/pasc/ ) makes it easy to navigate and perform analyses. Multiple new viral genome sequences can be tested simultaneously with this system to suggest the taxonomic position of virus isolates in a specific family. PASC eliminates potential discrepancies in the results caused by different algorithms and/or different data used by researchers. PMID- 25119677 TI - A novel combination of a new umbravirus, a new satellite RNA and potato leafroll virus causes tobacco bushy top disease in Ethiopia. AB - Etiological studies of a recently emerged bushy top disease of tobacco in Ethiopia indicated that a ~4.5-kb dsRNA from infected plants represents an umbravirus, whereas a smaller band (~0.5 kb) is that of a new satellite RNA. Potato leafroll virus was also consistently associated with the disease. The three agents, whose experimental host ranges are restricted to members of the family Solanaceae, always occurred together in field samples and are transmitted together by the aphid Myzus persicae nicotianae. The umbravirus, which represents a new species, is most closely related to groundnut rosette virus, and the name Ethiopian tobacco bushy top virus is proposed. PMID- 25119678 TI - Molecular detection and characterization of human gyroviruses identified in the ferret fecal virome. AB - The recently described novel gyroviruses may infect chickens and/or humans; however, their pathogenic potential is unknown. In our metagenomic investigation, we detected many of the novel gyroviruses in the fecal viromes of ferrets with lymph node and organ enlargement. The complete genomic sequences of selected gyrovirus strains showed 90.7-99.4 % similarity to homologous reference gyrovirus strains. This study did not demonstrate an association between gyrovirus shedding from ferrets and the observed background disease; however, it provides evidence for genetic diversity among gyroviruses and raises the possibility that pet ferrets may transmit gyroviruses to heterologous hosts, e.g., humans. PMID- 25119679 TI - Genetic characterization of porcine kobuvirus and detection of coinfecting pathogens in diarrheic pigs in Jiangsu Province, China. AB - In this study, 396 samples from diarrheic pigs on 46 pig farms in Jiangsu Province, China, were analyzed by RT-PCR. One-hundred eighty-one pigs from 37 farms tested positive for porcine kobuvirus (PKV). Phylogenetic analysis of the 3D gene from 19 isolates showed sequence homology of 88.0 %-100 % and 69.4 %-100 % for nucleotides and amino acids, respectively, while similarity to isolates of other kobuviruses was 69.6 %-78.8 % and 27.8 %-56.9 %, respectively. One-hundred eighty-five samples contained two or more pathogens, and 31/68 PKV-positive samples tested positive for other diarrheic pathogens, confirming the existence of PKV infection and coinfection. PMID- 25119681 TI - Near-infrared spectroscopy for monitoring renal transplant perfusion. PMID- 25119682 TI - Hypervitaminosis A is prevalent in children with CKD and contributes to hypercalcemia. AB - BACKGROUND: Vitamin A accumulates in renal failure, but the prevalence of hypervitaminosis A in children with predialysis chronic kidney disease (CKD) is not known. Hypervitaminosis A has been associated with hypercalcemia. In this study we compared dietary vitamin A intake with serum retinoid levels and their associations with hypercalcemia. METHODS: We studied the relationship between vitamin A intake, serum retinoid levels, and serum calcium in 105 children with CKD stages 2-5 on dialysis and posttransplant. Serum retinoid measures included retinol (ROH), its active retinoic acid (RA) metabolites [all-trans RA (at-RA) and 13-cis RA] and carrier proteins [retinol-binding protein-4 (RBP4) and transthyretin (TTR)]. Dietary vitamin A intake was assessed using a food diary. RESULTS: Twenty-five children were in CKD 2-3, 35 in CKD 4-5, 23 on dialysis and 22 posttransplant; 53 % had vitamin A intake above the Reference Nutrient Intake (RNI) value. Children receiving supplemental feeds compared with diet alone had higher vitamin A intake (p = 0.02) and higher serum ROH (p < 0.001). Notably, increased ROH was seen as early as CKD stage 2. For every 10 ml/min/1.73 m(2) fall in estimated glomerular filtration rate (eGFR), there was a 13 % increase in ROH. RBP4 levels were increased in CKD 3-5 and dialysis patients. The lowest ratios of ROH:RBP4 were seen in dialysis compared with CKD 2-3 (p = 0.03), suggesting a relative increase in circulating RBP4. Serum ROH, RBP4 and at-RA were associated with serum calcium. On multivariable analysis RBP4 levels and alfacalcidol dose were significant predictors of serum calcium (model R (2) 32 %) in dialysis patients. CONCLUSIONS: Hypervitaminosis A is seen in early CKD, with highest levels in children on supplemental feeds compared with diet alone. Serum retinoid levels significantly predict hypercalcemia. PMID- 25119683 TI - Procalcitonin as a postmortem sepsis marker. A comparison of the validity of results obtained from blood serum, aqueous humour and cerebrospinal fluid. AB - In recent years, serum levels of the prohormone procalcitonin have been investigated in a number of studies in relation to postmortem sepsis diagnostics, as macroscopic and histomorphological findings are, as a rule, nonspecific. However, due to advanced haemolysis, it is often not possible to determine serum procalcitonin (PCT) levels in cases of sepsis-related death. Moreover, the impact of postmortem interval on PCT levels is largely unclarified. In view of this, the present pilot study investigated PCT levels in the serum, aqueous humour, and cerebrospinal fluid in a study population of 25 persons who died of sepsis and a control population of 25 deaths unrelated to sepsis. Using the Mann-Whitney U test, statistically significant differences in PCT levels were determined for all the analysed samples from the study and control populations. Logistic regression analysis was used to calculate cut-off values for sepsis diagnosis for all the sample types. Furthermore, the serum elimination rates published by Tsokos et al. (Int J Legal Med 114:237-243, 2001) were used to calculate the PCT levels at the time of death for the cases with a known postmortem interval. The results of our study demonstrate that, taking account of the postmortem elimination process, it is possible to infer the value at the time of death from the procalcitonin levels measured in all three sample types and to interpret this with the aid of a defined cut-off value. The findings need to be verified based on a larger study population. PMID- 25119685 TI - Fatal contact shot to the chest caused by the gas jet from a muzzle-loading pistol discharging only black powder and no bullet: case study and experimental simulation of the wounding effect. AB - In modern medico-legal literature, only a small number of publications deal with fatal injuries from black powder guns. Most of them focus on the morphological features such as intense soot soiling, blast tattooing and burn effects in close range shots or describe the wound ballistics of spherical lead bullets. Another kind of "unusual" and potentially lethal weapons are handguns destined for firing only blank cartridges such as starter and alarm pistols. The dangerousness of these guns is restricted to very close and contact range shots and results from the gas jet produced by the deflagration of the propellant. The present paper reports on a suicide committed with a muzzle-loading percussion pistol cal. 45. An unusually large stellate entrance wound was located in the precordial region, accompanied by an imprint mark from the ramrod and a faint greenish discoloration (apparently due to the formation of sulfhemoglobin). Autopsy revealed an oversized powder cavity, multiple fractures of the anterior thoracic wall as well as ruptures of the heart, the aorta, the left hepatic lobe and the diaphragm. In total, the zone of mechanical destruction had a diameter of approx. 15 cm. As there was no exit wound and no bullet lodged in the body, the injury was caused exclusively by the inrushing combustion gases of the propellant (black powder) comparable with the gas jet of a blank cartridge gun. In contact shots to ballistic gelatine using the suicide's pistol loaded with black powder but no projectile, the formation of a nearly spherical cavity could be demonstrated by means of a high-speed camera. The extent of the temporary cavity after firing with 5 g of black powder roughly corresponded to the zone of destruction found in the suicide's body. PMID- 25119684 TI - Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series. AB - Epilepsy affects approximately 3% of the world's population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24% of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy. PMID- 25119686 TI - Diagnostic accuracy of pre-bronchodilator FEV1/FEV6 from microspirometry to detect airflow obstruction in primary care: a randomised cross-sectional study. AB - BACKGROUND: Forced expiratory volume in 1s/forced expiratory volume in 6 s ( FEV1/FEV6) assessment with a microspirometer may be useful in the diagnostic work up of subjects who are suspected of having COPD in primary care. AIM: To determine the diagnostic accuracy of a negative pre-bronchodilator (BD) microspirometry test relative to a full diagnostic spirometry test in subjects in whom general practitioners (GPs) suspect airflow obstruction. METHODS: Cross sectional study in which the order of microspirometry and diagnostic spirometry tests was randomised. Study subjects were (ex-)smokers aged >=50 years referred for diagnostic spirometry to a primary care diagnostic centre by their GPs. A pre BD FEV1/FEV6 value <0.73 as measured with the PiKo-6 microspirometer was compared with a post-BD FEV1/FVC (forced vital capacity) <0.70 and FEV1/FVC85%). Covariates associated with transitioning between states were examined. The association between CD3+ T-cell percentage states and time to ADI/death from cART initiation was determined using Cox proportional hazards models. RESULTS: A total of 4463 patients were followed for a median of 3 years. Two thousand, five hundred and eight (56%) patients never transitioned from their baseline CD3+ T cell percentage state; 85% of these had normal TCH. In multivariable analysis, individuals with time-updated low CD4+ cell count, time-updated detectable viral load, older age, and hepatitis C virus (HCV) coinfection were less likely to maintain TCH. In the multivariable proportional hazards model, both very low and high CD3+ T-cell percentages were associated with increased risk of ADI/death [adjusted hazard ratio=1.91 (95% confidence interval, CI: 1.27-2.89) and hazard ratio=1.49 (95% CI: 1.13-1.96), respectively]. CONCLUSION: Patients with very low or high CD3+ T-cell percentages are at risk for ADIs/death. To our knowledge, this is the first study linking altered TCH and morbidity/mortality in cART treated HIV-positive patients. PMID- 25119690 TI - Cost-effectiveness of novel algorithms for rapid diagnosis of tuberculosis in HIV infected individuals in Uganda. AB - OBJECTIVE: Xpert MTB/RIF ('Xpert') and urinary lateral-flow lipoarabinomannan (LF LAM) assays offer rapid tuberculosis (TB) diagnosis. This study evaluated the cost-effectiveness of novel diagnostic algorithms utilizing combinations of Xpert and LF-LAM for the detection of active TB among people living with HIV. DESIGN: Cost-effectiveness analysis using data from a comparative study of LF-LAM and Xpert, with a target population of HIV-infected individuals with signs/symptoms of TB in Uganda. METHODS: A decision-analysis model compared multiple strategies for rapid TB diagnosis:sputum smear-microscopy; sputum Xpert; smear-microscopy combined with LF-LAM; and Xpert combined with LF-LAM. Primary outcomes were the costs and DALY's averted for each algorithm. Cost-effectiveness was represented using incremental cost-effectiveness ratios (ICER). RESULTS: Compared with an algorithm of Xpert testing alone, the combination of Xpert with LF-LAM was considered highly cost-effective (ICER $57/DALY-averted) at a willingness to pay threshold of Ugandan GDP per capita. Addition of urine LF-LAM testing to smear microscopy was a less effective strategy than Xpert replacement of smear microscopy, but was less costly and also considered highly cost-effective (ICER $33 per DALY-averted) compared with continued usage of smear-microscopy alone. Cost-effectiveness of the Xpert plus LF-LAM algorithm was most influenced by HIV/ART costs and life-expectancy of patients after TB treatment. CONCLUSION: The addition of urinary LF-LAM to TB diagnostic algorithms for HIV-infected individuals is highly cost-effective compared with usage of either sputum smear microscopy or Xpert alone. PMID- 25119692 TI - Immunologic nonresponders and T-regulatory cells in HIV-1 infection. PMID- 25119693 TI - Viral and bacterial risks associated with mephedrone abuse in HIV-infected men who have sex with men. PMID- 25119687 TI - Frequently asked questions about in vivo chlorophyll fluorescence: practical issues. AB - The aim of this educational review is to provide practical information on the hardware, methodology, and the hands on application of chlorophyll (Chl) a fluorescence technology. We present the paper in a question and answer format like frequently asked questions. Although nearly all information on the application of Chl a fluorescence can be found in the literature, it is not always easily accessible. This paper is primarily aimed at scientists who have some experience with the application of Chl a fluorescence but are still in the process of discovering what it all means and how it can be used. Topics discussed are (among other things) the kind of information that can be obtained using different fluorescence techniques, the interpretation of Chl a fluorescence signals, specific applications of these techniques, and practical advice on different subjects, such as on the length of dark adaptation before measurement of the Chl a fluorescence transient. The paper also provides the physiological background for some of the applied procedures. It also serves as a source of reference for experienced scientists. PMID- 25119694 TI - Groundwater quality assessment and its correlation with gastroenteritis using GIS: a case study of Rawal Town, Rawalpindi, Pakistan. AB - Majority of the people of Pakistan get drinking water from groundwater source. Nearly 40 % of the total ailments reported in Pakistan are the result of dirty drinking water. Every summer, thousands of patients suffer from acute gastroenteritis in the Rawal Town. Therefore, a study was designed to generate a water quality index map of the Rawal Town and identify the relationship between bacteriological water quality and socio-economic indicators with gastroenteritis in the study area. Water quality and gastroenteritis patient data were collected by surveying the 262 tubewells and the major hospitals in the Rawal Town. The collected spatial data was analyzed by using ArcGIS spatial analyst (Moran's I spatial autocorrelation) and geostatistical analysis tools (inverse distance weighted, radial basis function, kriging, and cokriging). The water quality index (WQI) for the study area was computed using pH, turbidity, total dissolved solids, calcium, hardness, alkalinity, and chloride values of the 262 tubewells. The results of Moran's I spatial autocorrelation showed that the groundwater physicochemical parameters were clustered. Among IDW, radial basis function, and kriging and cokriging interpolation techniques, cokriging showed the lowest root mean square error. Cokriging was used to make the spatial distribution maps of water quality parameters. The WQI results showed that more than half of the tubewells in the Rawal Town were providing "poor" to "unfit" drinking water. The Pearson's coefficient of correlation for gastroenteritis with fecal coliform was found significant (P < 0.05) in Water and Sanitation Agency (WASA) zone 2, and with shortage of toilets, it was significant (P < 0.05) in WASA zones 1 and 3. However, it was significantly (P < 0.01) inversely related with literacy rate in WASA zones 1, 2, and 3. PMID- 25119696 TI - Enhancing the brightness of Si nanocrystal light-emitting devices with electro excited surface plasmons. AB - The use of electro-excited surface plasmons (SPs) in Ag nanoparticles (Ag-NPs) is shown to enhance the brightness of Si nanocrystal light-emitting devices (Si-NC LEDs). The Ag-NPs are prepared on the Si-NC thin film by ultrasonic irradiation and postannealing treatments. Electro-excited SPs on Ag-NPs are found, which are induced by electron impact on Ag-NPs and the front electrode Al layer during the charge injection process of LED. The electro-excited SPs enhance the electroluminescence of Si-NC, or LED brightness, via the SP field coupling to the exciton dipole moment of Si-NC. A maximal 5.2-fold brightness enhancement of Si NC LED is achieved at the postannealing temperature of 200 degrees C. Remnant far-field radiations arising from electro-excited SPs are detected, which further supports the existence of such SPs. PMID- 25119695 TI - Determination of heavy metal contents in some freshwater fishes. AB - The concentrations of heavy metals in tench, pike-perch, and common carp fish caught in four different seasons from Damsa dam lake (Nevsehir) were determined. Heavy metal contents of fishes changed depending on seasons. The highest Al (20.894 mg/kg) in tench was established in winter, and the lowest Al (1.605 mg/kg) was determined in summer. Fe content of tench fish changed between 112.906 mg/kg (autumn) and 31.207 mg/kg (spring). In addition, Zn contents of tench were found between 36.0323 mg/kg (summer) and 430.586 mg/kg (winter). The results indicate that concentrations of Cu of tench varied from 0.1934 mg/kg (winter) to 15.422 mg/kg (autumn). Results indicate that concentrations varied from 2.923 mg/kg (autumn) to 32.078 mg/kg (summer) with a mean of 11.1893 mg/kg for Al; 0.2483 mg/kg (spring) to 3.3088 mg/kg (autumn) with a mean of 1.6189 mg/kg for Ni; 0.5325 mg/kg (spring) to 0.845 mg/kg (autumn) with a mean of 0.7234 for Pb; and 7.0464 mg/kg (winter) to 253.686 mg/kg (summer) with a mean of 133.6348 for Zn. In common carp, Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Zn, Se, Ga, and Te contents were determined as 3.9623 mg/kg; 0.1293, 0.2336, 0.0526, 0.1543, 4.2406, 0.726, 1.797, 0.6216, 6.8536, 0.1783, 0.7876, and 0.371 mg/kg in autumn, respectively. PMID- 25119697 TI - Understanding p53: new insights into tumor suppression. AB - p53 (aka TP53) is a powerful tumor suppressor, and oncogenic transformation is induced when the ability of p53 to suppress tumorigenesis is compromised. p53 not only prevents tumorigenesis, but also tumor progression, that is, local invasion and distant metastasis. Recently, we showed that cytoplasmic p53 prevents RAS driven invasion via alteration of actin cytoskeleton remodeling. This follows modulation of mitochondrial integrity. The transcriptional activity of p53 has been restored using small molecules; however, their success as cancer therapies is largely dependent on the status of downstream targets of p53. It is therefore important to elucidate the role of these downstream targets in p53 regulated tumor progression. With the recently described mechanism of tumor suppression highlighting a role of p53's downstream targets in the regulation of actin cytoskeleton dynamics and lamellipodia formation, we suggest that potential therapeutic targets may be revealed within this mechanism that can be exploited in anticancer therapy. PMID- 25119698 TI - E-health interventions for suicide prevention. AB - Many people at risk of suicide do not seek help before an attempt, and do not remain connected to health services following an attempt. E-health interventions are now being considered as a means to identify at-risk individuals, offer self help through web interventions or to deliver proactive interventions in response to individuals' posts on social media. In this article, we examine research studies which focus on these three aspects of suicide and the internet: the use of online screening for suicide, the effectiveness of e-health interventions aimed to manage suicidal thoughts, and newer studies which aim to proactively intervene when individuals at risk of suicide are identified by their social media postings. We conclude that online screening may have a role, although there is a need for additional robust controlled research to establish whether suicide screening can effectively reduce suicide-related outcomes, and in what settings online screening might be most effective. The effectiveness of Internet interventions may be increased if these interventions are designed to specifically target suicidal thoughts, rather than associated conditions such as depression. The evidence for the use of intervention practices using social media is possible, although validity, feasibility and implementation remains highly uncertain. PMID- 25119699 TI - Prevalence and antibiogram profiling of Escherichia coli pathotypes isolated from the Kat River and the Fort Beaufort abstraction water. AB - Escherichia coli is a widespread bacterium encompassing a variety of strains, ranging from highly pathogenic strains, causing worldwide outbreaks of severe diseases to avirulent, well characterized safe laboratory strains. This study evaluated the prevalence and antibiogram profiles of E. coli pathotypes isolated from the Kat River and Fort Beaufort abstraction water. A total of 171 out of 278 confirmed E. coli isolates were positive for at least one pathogenic determinant and these included enteropathogenic E. coli (6%), enterotoxigenic E. coli (47%), uropathogenic E. coli (2%), neonatal meningitis E. coli (5%), diffusely adherent E. coli (1%) and enterohaemorrhagic E. coli (1%). Interestingly, enteroinvasive and enteroaggregative E. coli were not detected. The phenotypic antibiogram profiles of the isolates revealed that all were resistant to penicillin G, while 98% and 38% of the pathotypes were resistant to ampicillin and trimethoprim sulphamethoxazole, respectively. About 8% of the isolates were resistant to streptomycin. More than half of the isolates exhibited multiple antibiotic resistance with 44% being resistant to three antibiotics and 8% resistant to four antibiotics. We conclude that the Kat River is a reservoir of potentially virulent antibiotic resistant E. coli strains that can cause serious health risks to humans who drink raw water from this river, or in the case that consumption of treated drinking water coincides with failed drinking water processes. PMID- 25119701 TI - [Aging and climate change: impact on health-related quality of life]. PMID- 25119700 TI - Type and course of symptoms demonstrated in the terminal and dying phases by people with dementia in nursing homes. AB - BACKGROUND: In all, 39 % of people living in Swiss nursing homes suffer from dementia. Detailed data about type and course of symptoms displayed by these patients in their terminal phase are lacking. METHODS: This descriptive, retrospective study analysed 65 nursing documents from deceased people with dementia in four nursing homes in the canton of Zurich, Switzerland. RESULTS: Difficulties with mobility (81 %), pain (71 %) and sleep disturbance (63 %) were the most frequent of the 10 identified symptoms. Towards the end of life, difficulties with mobility, sleep disturbance, agitation and other neuropsychiatric symptoms, such as episodes of depression, decreased (decrescent pattern), while pain, feeding problems, breathing abnormalities, apathy and anxiety increased (crescent pattern). Courses of pain were documented in 17 % of the nursing records. In addition, 76 % of the residents had been visited on a daily basis by next of kin in their last 7 days, compared with only one third of residents previously. Furthermore, daily communication between healthcare professionals and next of kin tripled during this period. CONCLUSION: The documented prevalence of a high and increasing level of pain towards the end of life, combined with the lack of documented courses of pain, shows potential for improvement in pain relief and pain identification for patients with dementia in their terminal phase. The increasing number of visits by next of kin and the increasingly intensive contact between healthcare professionals and next of kin in the last 7 days are a strong indicator that the end of life can be predicted relatively well by the involved participants and appropriate reactions follow. PMID- 25119702 TI - Heat waves and mortality in Frankfurt am Main, Germany, 2003-2013: what effect do heat-health action plans and the heat warning system have? AB - Following the heat wave of August 2003 that caused over 70,000 fatalities in Western Europe, heat-health action plans (HHAP) and heat warning systems were implemented in many European countries, including Germany. The effect of these preventive measures (informing the population as well as nursing and medical personnel) on excess mortality during heat waves in Frankfurt am Main, Germany, is studied, taking into account newly published data on a modifying effect of air pollution on heat mortality. MATERIAL AND METHOD: Mortality data comprising all deaths registered in the city of Frankfurt was obtained from the statistical state office; air temperature and air pollution data in Frankfurt Ost were obtained from the Hessian state office for environment and geology. SPSS Version 15 was used for statistical analysis (bivariate and partial correlations, nonparametric tests/Kruskal-Wallis, and Mann-Whitney test). RESULTS: Temperature data as well as air pollution and daily mortality exhibited extreme values in summer 2003 compared to the summer periods 2004-2013. Never again were such levels of temperature and air pollution reached. In 2003, excess mortality was 78%, and as high as 113% among the population aged >80 years. During the heat wave of 2010, the total excess mortality was 23% (significant) and 38% in the population aged >80 years, while during heat waves in 2006 and 2013 no significant increase in total mortality was seen (total excess mortality 12% and 4%; not significant). CONCLUSION: Lower excess mortality could be seen in Frankfurt am Main during heat waves following the implementation of HHAP and the heat warning system. This might be an effect of the measures implemented by the HHAP to reduce heat mortality. However, it cannot be ruled out that this might also be an effect of shorter heat wave periods and lower air pollution in the subsequent years. Therefore, further efforts are needed to improve the resilience of the population, especially the elderly population, to better cope with heat waves. PMID- 25119703 TI - The challenges posed by climate change to successful ageing. AB - Ever since the 2003 heat wave that caused 70,000 heat deaths, the dramatic consequences of climate change and rising temperatures in Europe have become an intensively researched topic. During heat waves, the older urban adult population is at highest risk. The STOPHOT project is the first investigation in Austria to establish a comprehensive knowledge base on heat perception, awareness of heat risks and adaptive/coping behaviours among older adults. The main research questions include: (1) Does climate change endanger the chances of successful ageing in urban areas? (2) How do age, social inequalities and the living environment intersect with environmental stressors in affecting successful ageing? (3) Which heat adaption strategies do older adults deploy and to what extent can they mediate heat stress in an effort to increase chances of successful ageing under the conditions of climate change? The results indicate that climate change and rising temperatures are in fact one important determinant of whether and how an older person can maintain well-being in later life. Older adults (> 65 years) with a low socio-economic status and poor health conditions, who tend to be socially isolated, are most at risk. However, no 'heat island effect' of the residential environment could be found. How much a person suffers from heat stress is highly dependent on the adaption strategies deployed. Adaption strategies of older urban residents mostly centred on body-related measures, such as drinking more or wearing lighter clothes, and indoor-centred measures, particularly avoiding the outdoors. PMID- 25119704 TI - Comprehension of climate change and environmental attitudes across the lifespan. AB - Given the coincidence of the demographic change and climate change in the upcoming decades the aging voter gains increasing importance in climate change mitigation and adaptation processes. It is generally assumed that information status and comprehension of complex processes underlying climate change are prerequisites for adopting pro-environmental attitudes and taking pro environmental actions. In a cross-sectional study, we investigated in how far (1) environmental knowledge and comprehension of feedback processes underlying climate change and (2) pro-environmental attitudes change as a function of age. Our sample consisted of 92 participants aged 25-75 years (mean age 49.4 years, SD 17.0). Age was negatively related to comprehension of system structures inherent to climate change, but positively associated with level of fear of consequences and anxiousness towards climate change. No significant relations were found between environmental knowledge and pro-environmental attitude. These results indicate that, albeit understanding of relevant structures of the climate system is less present in older age, age is not a limiting factor for being engaged in the complex dilemma of climate change. Results bear implications for the communication of climate change and pro-environmental actions in aging societies. PMID- 25119705 TI - [Health protection during heat waves: European recommendations and experience in Hesse]. AB - BACKGROUND: In the course of climate change periods of extreme heat will probably happen more frequently. The aim of heat health action plans is to prevent the health consequences of heat. OBJECTIVES: The purpose of the present work is to develop a proposal for a heat health action plan for Hesse, Germany. MATERIALS AND METHODS: In 34 interviews with experts the existing heat health warning system was evaluated. Heat health action plans of 8 European countries were analysed. On this basis a concept for a heat health action plan for Hesse was developed. RESULTS: In Hesse only nursing homes take preventative measures reliably, other health care sectors act along varying individual criteria. Heat health action plans include a heat health warning system and measures. They arrange competences and risk communication. Local authorities are responsible for implementation. Some plans include a surveillance system of mortality or morbidity. In a heat health action plan for Hesse measures should be specified and adapted to specific needs on the local level. Physicians in outpatient clinics are in a key position having contact with the vulnerable group of the elderly. CONCLUSION: A heat health action plan offers opportunities for effective prevention if responsibilities are defined and evaluated, and monitoring of mortality and morbidity is integrated. In the structures of the German health care system efforts to prevent heat-related illness cannot succeed without reliable participation of the outpatient medical system. PMID- 25119706 TI - Efficacy of new pediatric extra-corporeal life support system (Endumo 2000) for postoperative management after Norwood operation. AB - This study aimed to assess the efficacy of a new pediatric extra-corporeal life support (ECLS) system (Endumo 2000, Heiwa Bussan, Tokyo, Japan) for postoperative management after the Norwood operation. Thirty-three consecutive patients with hypoplastic left heart syndrome or its variant undergoing the Norwood operation between August 2007 and December 2013 were divided into two groups according to available ECLS devices. Before November 2009, pediatric Emersave (TERUMO, Saitama, Japan) was employed as the ECLS device, and 14 patients were operated on during this period (Emersave era: 7 boys; 2.9 kg). After December 2009, Endumo 2000 was employed and 19 patients were operated on (Endumo era: 8 boys, 3.1 kg). The demographic characteristics of both groups showed no significant differences. ECLS was initiated in 7 of 14 patients (50%) during the Emersave era and 7 of 19 patients (37%) during the Endumo era (p = 0.45). Chest reentry for hemostasis during ECLS support was more frequently needed in patients supported by Emersave (5/7) than Endumo (1/7) (p = 0.03). The first ECLS circuit durability of Endumo was significantly longer than that of Emersave (p = 0.01). The survival at discharge rate in patients required ECLS was 0% (0/7) when supported by Emersave, but 57% (4/7) by Endumo (p = 0.02). As a result, the survival at discharge rate was 43% (6/14) in the Emersave era and 79% (14/19) in the Endumo era (p = 0.03). Longer durability and superior antithrombogenicity of the Endumo 2000 contributed to the improvement of surgical outcomes after the Norwood operation. PMID- 25119707 TI - Trace elements concentration in nails and association with airway inflammation in adolescents. AB - Asthma is a multifactorial disease and its severity varies with the inflammatory status of the patient. It has been hypothesized that deficiency of trace elements has an important role in the etiology of asthma. The aim of the study was to evaluate the concentration of trace elements in nails of adolescents with different degrees of airway inflammation. We assessed the prevalence of active and severe asthma in adolescents (n = 106) through the ISAAC questionnaire. Subjects were allocated into two different groups according to the value of fraction exhaled nitric oxide (FeNO) measured. Also, nail specimens were collected in order to determine the concentration of accumulated trace elements (Cu, Zn, Mn, Se) by ICP-MS. It was performed Student's t test to evaluate statistical differences between inflammatory groups considering normally distributed data. On the other hand, when data presented non-normal distribution, Mann-Whitney U test was utilized. Spearman coefficients were calculated to investigate correlations between FeNO and mineral concentrations. Exhaled NO was increased in male subjects. We found association between active asthma and elevated exhaled NO. There was no significant difference in Cu (4.40 vs. 4.52), Zn (84.66 vs. 79.48), Mn (0.59 vs. 0.76), and Se (0.18 vs. 0.19) concentrations (MUg/g) among distinct FeNO groups as well as was not observed correlation between exhaled NO levels and any element. Deficiency of trace elements in nails were not associated with increased FeNO. PMID- 25119708 TI - Anatomical region differences and age-related changes in copper, zinc, and manganese levels in the human brain. AB - Using inductively coupled plasma-mass spectrometry after samples microwave assisted acid digestion, zinc (Zn), copper (Cu), and manganese (Mn) levels were measured in 14 different areas of the human brain of adult individuals (n = 42; 71 +/- 12, range 50-101 years old) without a known history of neurodegenerative, neurological, or psychiatric disorder. The main goals of the work were to establish the "normal" (reference) values for those elements in the human brain and to evaluate the age-related changes, a prior and indispensable step in order to enlighten the role of trace element (TE) in human brain physiology and their involvement in aging and neurodegenerative processes. Considering the mean values for the 14 regions, Zn (mean +/- sd; range 53 +/- 5; 43-61 MUg/g) was found at higher levels, followed by Cu (22 +/- 5; 10-37 MUg/g) and Mn (1.3 +/- 0.3; 0.5 2.7 MUg/g). The TE distribution across the brain tissue showed to be quite heterogeneous: the highest levels of Zn were found in the hippocampus (70 +/- 10; 49-95 MUg/g) and superior temporal gyrus (68 +/- 10; 44-88 MUg/g) and the lowest in the pons (33 +/- 8; 19-51 MUg/g); the highest levels of Cu and Mn were found in the putamen (36 +/- 13; 21-76 MUg/g and 2.5 +/- 0.8; 0.7-4.5 MUg/g, respectively) and the lowest in the medulla (11 +/- 6; 2-30 MUg/g and 0.8 +/- 0.3; 0.2-1.8 MUg/g, respectively). A tendency for an age-related increase in Zn and Mn levels was observed in most brain regions while Cu levels showed to be negatively correlated with age. PMID- 25119709 TI - Analysis of the DNA interaction of copper compounds belonging to the Casiopeinas(r) antitumoral series. AB - Casiopeinas(r) are mixed-chelate copper complexes with antitumor tested potential. Their activity, both in vitro and in vivo, as antiproliferative, cytotoxic, and genotoxic drugs has been assessed. Biological results of these copper compounds have deserved some of them entering clinical trials. Significant efforts have been devoted to the in-depth identification of their mechanism of action. Using gel electrophoresis analysis, we have previously shown that the interaction of the Casiopeinas(r) Cas II-gly, [Cu(4,7-dimethyl-1,10 phenanthroline)(glycinate)]NO3 with DNA, triggers the cleavage of the biomolecule by a free radical mechanism. In this work, we further study the behavior of different complexes of the same Casiopeinas(r) series also including glycinate as co-ligand {Cas VI-gly (5,6 dimethyl-1,10-phenanthroline glycinato copper(II) nitrate), Cas VII-gly (1,10-phenanthroline glycinato copper(II) nitrate), and Cas IX-gly (2,2'-bipyridine glycinato copper(II) nitrate)} and of a Casiopeinas(r) with a different co-ligand (Cas III-Cs; 4,7-dimethyl-1,10-phenanthroline salicylaldehydato-copper(II) nitrate). While all of them produce DNA degradation, the performance in the presence of a radical scavenger suggests the existence of differences in their mechanism of interaction with DNA. PMID- 25119710 TI - It is my great pleasure to welcome you to the third issue of 2014. Introduction. PMID- 25119711 TI - Effects of Ti surface treatments with silane and arginylglycylaspartic acid peptide on bone cell progenitors. AB - Achieving optimal aesthetic appearance is a major objective in dental implant design, and the interaction between the materials and the bone cell progenitors is an important factor in the attainment of this objective. In this study, a novel concept was evaluated by varying the surface modifications on titanium (Ti). Different levels of roughness can be attained by machine grinding (M), sand blasting, and acid etching (SLA) of the samples. The behavior of bone cell progenitors (D1) on the surfaces of Ti disks with different surface modifications was investigated. The surfaces of M or SLA disks were silanized (MS or SLAS group) through treatment with silane/Gly-Arg-Gly-Asp-Ser (GRGDS) peptide (MSP or SLASP group) and anchored particles of tetracalcium phosphate (TTCP) on the specimen surfaces (SLA-TTCP group). Physicochemical analysis was performed by metallographic microscopy, scanning electron microscopy, and contact angle analysis. The proliferation and the quantitative alkaline phosphatase (ALP) production of D1 cells on the surface of different sample groups were determined. The SLASP group had a significantly larger D1 cell proliferation than the other groups after 4 and 7 d of incubation (p < 0.05). ALP expression was a very early marker of differentiation, and was the first indication of the increasing number of cells at 7 d of culture. Among the groups in the M substrate series (i.e., M, MS, and MSP) and in the SLA series (i.e., SLA, SLAS, and SLASP), the MSP and SLASP specimens exhibited superior differentiation abilities on respective cultures until day 7 and day 10. A high number of hydrophilic surfaces dominated cell proliferation in the early stage of cell attachment. However, factors affecting the pore structure and the surface morphology can improve cell proliferation and differentiation. According to analyses of proliferation and ALP expression of bone cell progenitors D1, the original SLA implant surface can be improved with surface treatment methods, such as silanization and treatment with graft GRGDS pentapeptide. These methods can be potential candidates for the promotion of bone growth. PMID- 25119712 TI - Correlation between SNP genotypes and periodontitis in Japanese type II diabetic patients: a preliminary study. AB - The present study aims to investigate the correlation between SNP genotype patterns and periodontitis severity in Japanese type II diabetic patients. A cross-sectional study in 43 Japanese diabetic patients with periodontitis was performed. Blood samples were drawn for single nucleotide polymorphism (SNP) analyses and periodontal index (probing pocket depth and clinical attachment level) was subsequently recorded. Twelve functional genes with SNPs that had been shown to be associated with diabetes and/or inflammation were genotyped using a nuclease-mediated SNP-specific ligation method. Subjects with two or more sites with clinical attachment level >=6 mm and who additionally had one or more sites with pocket depth >=5 mm were classified as having severe periodontitis. Proportions of risk genotypes/non-risk genotypes between severe and non-severe periodontitis were subsequently compared. A high frequency (21/43 participants, 49%) of adiponectin gene polymorphism (ADIPOQ 45T > G) homozygous risk genotype (TT genotype) was observed in the participants. The frequency of TGF-beta1 SNP (29C > T) risk genotype (TT genotype) in severe periodontitis (34%, n = 11) was significantly higher than in non-severe periodontitis (0%, n = 0) (p = 0.04). Our study suggests that TGF-beta1 SNPs (29C > T) may be used as one of the risk indicators for severe periodontitis in Japanese diabetic patients. PMID- 25119714 TI - A time series evaluation of the FAST National Stroke Awareness Campaign in England. AB - OBJECTIVE: In February 2009, the Department of Health in England launched the Face, Arm, Speech, and Time (FAST) mass media campaign, to raise public awareness of stroke symptoms and the need for an emergency response. We aimed to evaluate the impact of three consecutive phases of FAST using population-level measures of behaviour in England. METHODS: Interrupted time series (May 2007 to February 2011) assessed the impact of the campaign on: access to a national stroke charity's information resources (Stroke Association [SA]); emergency hospital admissions with a primary diagnosis of stroke (Hospital Episode Statistics for England); and thrombolysis activity from centres in England contributing data to the Safe Implementation of Thrombolysis in Stroke UK database. RESULTS: Before the campaign, emergency admissions (and patients admitted via accident and emergency [A&E]) and thrombolysis activity was increasing significantly over time, whereas emergency admissions via general practitioners (GPs) were decreasing significantly. SA webpage views, calls to their helpline and information materials dispatched increased significantly after phase one. Website hits/views, and information materials dispatched decreased after phase one; these outcomes increased significantly during phases two and three. After phase one there were significant increases in overall emergency admissions (505, 95% CI = 75 to 935) and patients admitted via A&E (451, 95% CI = 26 to 875). Significantly fewer monthly emergency admissions via GPs were reported after phase three (-19, 95% CI = -29 to -9). Thrombolysis activity per month significantly increased after phases one (3, 95% CI = 1 to 6), and three (3, 95% CI = 1 to 4). CONCLUSIONS: Phase one had a statistically significant impact on information seeking behaviour and emergency admissions, with additional impact that may be attributable to subsequent phases on information seeking behaviour, emergency admissions via GPs, and thrombolysis activity. Future campaigns should be accompanied by evaluation of impact on clinical outcomes such as reduced stroke related morbidity and mortality. PMID- 25119713 TI - Analysis of the relationship between periodontal disease and atherosclerosis within a local clinical system: a cross-sectional observational pilot study. AB - It has been revealed that atherosclerosis and periodontal disease may have a common mechanism of "chronic inflammation". Several reports have indicated that periodontal infection is related to atherosclerosis, but none have yet reported such an investigation through the cooperation of local clinics. This study was performed in local Japanese clinics to examine the relationship between periodontal disease and atherosclerosis under collaborative medical and dental care. A pilot multicenter cross-sectional study was conducted on 37 medical patients with lifestyle-related diseases under consultation in participating medical clinics, and 79 periodontal patients not undergoing medical treatment but who were seen by participating dental clinics. Systemic examination and periodontal examination were performed at baseline, and the relationships between periodontal and atherosclerosis-related clinical markers were analyzed. There was a positive correlation between LDL-C level and plasma IgG antibody titer to Porphyromonas gingivalis. According to the analysis under adjusted age, at a cut off value of 5.04 for plasma IgG titer to Porphyromonas gingivalis, the IgG titer was significantly correlated with the level of low-density lipoprotein cholesterol (LDL-C). This study suggested that infection with periodontal bacteria (Porphyromonas gingivalis) is associated with the progression of atherosclerosis. Plasma IgG titer to Porphyromonas gingivalis may be useful as the clinical risk marker for atherosclerosis related to periodontal disease. Moreover, the application of the blood examination as a medical check may lead to the development of collaborative medical and dental care within the local medical clinical system for the purpose of preventing the lifestyle-related disease. PMID- 25119715 TI - Do simultaneously viewed objects influence scene recognition individually or as groups? Two perceptual studies. AB - The ability to quickly categorize visual scenes is critical to daily life, allowing us to identify our whereabouts and to navigate from one place to another. Rapid scene categorization relies heavily on the kinds of objects scenes contain; for instance, studies have shown that recognition is less accurate for scenes to which incongruent objects have been added, an effect usually interpreted as evidence of objects' general capacity to activate semantic networks for scene categories they are statistically associated with. Essentially all real-world scenes contain multiple objects, however, and it is unclear whether scene recognition draws on the scene associations of individual objects or of object groups. To test the hypothesis that scene recognition is steered, at least in part, by associations between object groups and scene categories, we asked observers to categorize briefly-viewed scenes appearing with object pairs that were semantically consistent or inconsistent with the scenes. In line with previous results, scenes were less accurately recognized when viewed with inconsistent versus consistent pairs. To understand whether this reflected individual or group-level object associations, we compared the impact of pairs composed of mutually related versus unrelated objects; i.e., pairs, which, as groups, had clear associations to particular scene categories versus those that did not. Although related and unrelated object pairs equally reduced scene recognition accuracy, unrelated pairs were consistently less capable of drawing erroneous scene judgments towards scene categories associated with their individual objects. This suggests that scene judgments were influenced by the scene associations of object groups, beyond the influence of individual objects. More generally, the fact that unrelated objects were as capable of degrading categorization accuracy as related objects, while less capable of generating specific alternative judgments, indicates that the process by which objects interfere with scene recognition is separate from the one through which they inform it. PMID- 25119716 TI - Movements of blue sharks (Prionace glauca) across their life history. AB - Spatial structuring and segregation by sex and size is considered to be an intrinsic attribute of shark populations. These spatial patterns remain poorly understood, particularly for oceanic species such as blue shark (Prionace glauca), despite its importance for the management and conservation of this highly migratory species. This study presents the results of a long-term electronic tagging experiment to investigate the migratory patterns of blue shark, to elucidate how these patterns change across its life history and to assess the existence of a nursery area in the central North Atlantic. Blue sharks belonging to different life stages (n = 34) were tracked for periods up to 952 days during which they moved extensively (up to an estimated 28.139 km), occupying large parts of the oceanic basin. Notwithstanding a large individual variability, there were pronounced differences in movements and space use across the species' life history. The study provides strong evidence for the existence of a discrete central North Atlantic nursery, where juveniles can reside for up to at least 2 years. In contrast with previously described nurseries of coastal and semi-pelagic sharks, this oceanic nursery is comparatively vast and open suggesting that shelter from predators is not its main function. Subsequently, male and female blue sharks spatially segregate. Females engage in seasonal latitudinal migrations until approaching maturity, when they undergo an ontogenic habitat shift towards tropical latitudes. In contrast, juvenile males generally expanded their range southward and apparently displayed a higher degree of behavioural polymorphism. These results provide important insights into the spatial ecology of pelagic sharks, with implications for the sustainable management of this heavily exploited shark, especially in the central North Atlantic where the presence of a nursery and the seasonal overlap and alternation of different life stages coincides with a high fishing mortality. PMID- 25119718 TI - At-sea associations in foraging little penguins. AB - Prey distribution, patch size, and the presence of conspecifics are important factors influencing a predator's feeding tactics, including the decision to feed individually or socially. Little is known about group behaviour in seabirds as they spend most of their lives in the marine environment where it is difficult to observe their foraging activities. In this study, we report on at-sea foraging associations of little penguins (Eudyptula minor) during the breeding season. Individuals could be categorised as (1) not associating; (2) associating when departing from and/or returning to the colony; or (3) at sea when travelling, diving or performing synchronised dives. Out of 84 separate foraging tracks, 58 (69.0%) involved associations with conspecifics. Furthermore, in a total of 39 (46.4%), individuals were found to dive during association and in 32 (38.1%), individuals were found to exhibit synchronous diving. These behaviours suggest little penguins forage in groups, could synchronise their underwater movements and potentially cooperate to concentrate their small schooling prey. PMID- 25119720 TI - Recognition of elementary arm movements using orientation of a tri-axial accelerometer located near the wrist. AB - In this paper we present a method for recognising three fundamental movements of the human arm (reach and retrieve, lift cup to mouth, rotation of the arm) by determining the orientation of a tri-axial accelerometer located near the wrist. Our objective is to detect the occurrence of such movements performed with the impaired arm of a stroke patient during normal daily activities as a means to assess their rehabilitation. The method relies on accurately mapping transitions of predefined, standard orientations of the accelerometer to corresponding elementary arm movements. To evaluate the technique, kinematic data was collected from four healthy subjects and four stroke patients as they performed a number of activities involved in a representative activity of daily living, 'making-a-cup of-tea'. Our experimental results show that the proposed method can independently recognise all three of the elementary upper limb movements investigated with accuracies in the range 91-99% for healthy subjects and 70-85% for stroke patients. PMID- 25119719 TI - Modified treatment approach using cardiovascular disease risk calculator for primary prevention. AB - BACKGROUND: The recent guidelines for preventing atherosclerotic cardiovascular events are an important advancement. For primary prevention, statins are recommended if the ten-year risk is >= 5% (consideration for therapy) or >= 7.5% (definitive treatment unless contraindication after discussion). We rationalized that a significant cohort with ten-year risk below the treatment thresholds would predictably surpass them within the recommended 4-6 year window for reassessing the ten-year risk. As atherosclerosis is a progressive disease, these individuals may therefore benefit with more aggressive therapies even at baseline. METHODS AND FINDINGS: We used publicly available NHANES dataset for ten-year risk calculation. There were 1805 participants. To evaluate the ten-year risk change at five years, we considered two scenarios: no change in the baseline parameters except increased age by five (No Change) and alternatively 10% improvement in systolic BP, total and HDL-c, no smoking with five-year increase in age (Reduced Risk Profile). Amongst non-diabetics with <5% risk at baseline, 35% reached or exceeded 5% risk in five years (5% reached or exceed the 7.5% risk) with No Change and 9% reached or exceeded 5% risk in five years (none reached 7.5% risk) with Reduced Risk Profile; furthermore, 94% of the non-diabetic cohort with baseline risk between 3.5%-5% would exceed the 5% and/or 7.5% boundary limit with No Change. Amongst non-diabetics with 5-7.5% baseline risks, 87% reached or exceeded 7.5% with No Change while 30% reached or exceeded 7.5% risk with Reduced Risk Profile. CONCLUSIONS: A significant population cohort at levels below the treatment thresholds will predictably exceed these limits with time with or without improvement in modifiable risk factors and may benefit with more aggressive therapy at baseline. We provide an improved risk calculator that allows for integrating expected risk modification into discussion with an individual. This needs to be prospectively tested in clinical trials. PMID- 25119717 TI - Divergent effects of liraglutide, exendin-4, and sitagliptin on beta-cell mass and indicators of pancreatitis in a mouse model of hyperglycaemia. AB - AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose tolerance by still incompletely understood mechanisms. Each class of antihyperglycemic drugs has also been proposed to increase pancreatitis risk. Here, we compare systematically the effects of two widely-used GLP-1 analogues, liraglutide and exendin-4, and the DPP4 inhibitor, sitagliptin, in the mouse. METHODS: C57BL6 mice were maintained for 131 days on a normal diet (ND) or a diet comprising 60% fat (HFD) before measurements of fasting blood glucose and insulin, and intraperitoneal glucose tolerance. Beta- and alpha- cell volume, and Reg3b immunoreactivity, were measured by immunohistochemical analysis of pancreatic slices. RESULTS: Whereas liraglutide (200 ug/kg) and exendin-4 (10 ug/kg) treatment reduced body weight and/or improved glucose tolerance, sitagliptin (10 mg/kg) was without effect on either parameter. Liraglutide caused a sharp reduction in beta-cell mass in both ND and HFD mice, whereas exendin-4 exerted no effect. By contrast, sitagliptin unmasked an action of high fat diet to increase beta-cell mass. Reg3B positive area was augmented by all three agents in normal chow-fed mice, whilst sitagliptin and exendin-4, but not liraglutide, affected this parameter in HFD animals. Correspondingly sitagliptin, but not the GLP-1 analogues, increased circulating amylase levels in ND and HFD mice. CONCLUSIONS: Liraglutide improves glucose tolerance in the mouse whilst exerting relatively modest effects on pancreatitis risk. Conversely, exendin-4 and sitagliptin, at doses which exert, respectively, minor or no effects on metabolic parameters, lead to signs of pancreatitis. PMID- 25119721 TI - Dolichoectasia and the risk of stroke and vascular disease: a critical appraisal. AB - Dolichoectasia (DE) in cerebral arteries is a poorly understood arteriopathy that has been associated with increased risk of vascular morbidity and mortality. Dolichoectasia tends to affects older individuals with vascular risk factors, but it can also be secondary to specific conditions related with extracellular matrix health. The range of methods used to study DE and the biases inherent to hospital based samples weaken the generalizability of DE study results to the general population. Within the context of these limitations, there is growing evidence that DE is a serious condition that can increase the risk of vascular death. Recurrent strokes and compressive symptoms are among the major causes of morbidity, but cardiac ischemic disease and aortic aneurysms are not uncommon in populations with DE. The devastating outcomes of patients with DE are a call to action aimed at improving the quality of research on the topic and discovering therapies that can palliate the burden of DE in the population. PMID- 25119723 TI - Targeted delivery of doxorubicin to A549 lung cancer cells by CXCR4 antagonist conjugated PLGA nanoparticles. AB - Doxorubicin is used to treat a variety of cancers, but dose limiting toxicity or intrinsic and acquired resistance limits its application in many types of cancer. CXCR4 is a chemokine receptor which implicates in metastasis of cancers including lung cancer. LFC131, a peptide inhibitor of CXCR4-ligand binding, is a linear type of low molecular weight CXCR4 antagonist. In this study, we investigated the possibility of using LFC131 conjugated nanoparticles for targeted delivering doxorubicin to CXCR4 expressing lung cancer cells. The LFC131 peptide was conjugated to sodium carboxylmethyl cellulose coated poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles. Binding and cellular uptake of doxorubicin-loaded LFC131 conjugated nanoparticles (LFC131-DOX NP) in adenocarcinomic human alveolar basal epithelial cells called A549 cells were higher and faster than that of untargeted nanoparticles. The specificity of CXCR4-mediated internalization of LFC131-DOX NPs was confirmed by using free LFC131 peptide or anti-CXCR4 monoclonal antibody. Cell studies suggested that sustained release of doxorubicin afforded by PLGA nanoparticles may enable LFC131-DOX NP as a targeted and controlled release drug delivery system. PMID- 25119722 TI - The evaluation and treatment of endocrine forms of hypertension. AB - Endocrine hypertension is an important secondary form of hypertension, identified in between 5% and 10% of general hypertensive population. Primary aldosteronism is the most common cause of endocrine hypertension, accounting for 1%-10% in uncomplicated hypertension and 7%-20% in resistant hypertension. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Diagnosis requires a high index of suspicion and the use of appropriate screening tests based on clinical presentation. Failure to make proper diagnosis may lead to catastrophic complications or irreversible hypertensive target organ damage. Accordingly, patients who are suspected to have endocrine hypertension should be referred to endocrinologists or hypertension specialists who are familiar with management of the specific endocrine disorders. PMID- 25119725 TI - Towards a sustainable world through human factors and ergonomics: it is all about values. AB - In this paper, we analyse two approaches that attempt to address how a human factors and ergonomics (HFE) perspective can contribute to the sustainability of the human race. We outline the principles, purposes and fields of application of ergoecology and green ergonomics, and thereafter deal with their context of emergence, and the overlaps in purpose, and principles. Shared values are deduced and related to socio-technical principles for systems' design. Social responsibility and environmental/ecospheric responsibility are the leading threads of ergoecology and green ergonomics, giving rise to the values of: respect for human rights, respect for the Earth, respect for ethical decision making, appreciation of complexity, respect for transparency and openness, and respect for diversity. We discuss the consequences of considering these values in HFE theory and practice. PMID- 25119724 TI - Nonparametric method for detecting imprinting effect using all members of general pedigrees with missing data. AB - Imprinting effects can lead to parent-of-origin patterns in complex human diseases. For a diallelic marker locus, Pedigree Parental-Asymmetry Test (PPAT) and its extension MCPPAT using pedigrees allowing for missing genotypes are simple and powerful for detecting imprinting effects. However, these approaches only take affected offspring into consideration, thus not making full use of the data available. In this paper, we propose Monte Carlo Pedigree Parental-Asymmetry Test using both affected and unaffected (MCPPATu) offsprings, which allows for missing genotypes through Monte Carlo sampling. Simulation studies demonstrate that MCPPATu controls the empirical type I error rate well under the null hypotheses of no parent-of-origin effects. It is also demonstrated that the use of additional information from unaffected offspring and partially observed genotypes in the analysis can greatly improve the statistical power. Indeed, for common diseases, MCPPATu is much more powerful than MCPPAT when all genotypes are observed and the power improvement is even greater when there is missing data. For rarer diseases, there are still substantial power gains with the inclusion of unaffected offspring, although the gains are less impressive compared with those for more common diseases. PMID- 25119728 TI - Effect of obesity on aromatase inhibitor efficacy in postmenopausal, hormone receptor-positive breast cancer: a systematic review. AB - Aromatase inhibitors (AIs) decrease the production of oestrogen, decreasing stimulation of hormone receptor-positive breast cancer. Theoretically, AIs may be less effective in obese women, due to the greater quantity of aromatase in peripheral fatty tissue. We performed a systematic review to assess the effect of obesity on AI efficacy in breast cancer treatment. The review followed PRISMA guidelines. Studies included were interventional or observational studies with comparison groups, of postmenopausal women with hormone receptor-positive breast cancer on treatment with an AI, alone or in combination with other drugs, in which body mass index or another measure of obesity was recorded. Studies in all languages were included; if published as an abstract only, authors were contacted for further information. Outcome measures included overall survival, disease-free survival or time to progressive disease, survival from the start of therapy, mortality measures, local or distant recurrence of primary cancer and time to recurrence. Of 2,344 citations identified from five databases, eight studies met the criteria for inclusion; three randomised controlled trials and five retrospective cohort studies. Due to variability in study factors, it was not possible to perform a quantitative meta-analysis. However, the systematic review showed a trend towards a negative effect of obesity on AI efficacy. There is evidence of a negative effect of obesity on AI efficacy in postmenopausal hormone receptor-positive breast cancer, but the size of the effect cannot be assessed. More information is needed before clinical recommendations are made. PMID- 25119727 TI - Women's empowerment and contraceptive use: the role of independent versus couples' decision-making, from a lower middle income country perspective. AB - INTRODUCTION: There is little available evidence of associations between the various dimensions of women's empowerment and contraceptive use having been examined--and of how these associations are mediated by women's socio-economic and demographic statuses. We assessed these phenomena in Pakistan using a structured-framework approach. METHODS: We analyzed data on 2,133 women who were either using any form of contraceptive or living with unmet need for contraception. The survey was conducted during May - June 2012, with married women of reproductive age (15-49 years) in three districts of Punjab. The dimensions of empowerment were categorized broadly into: economic decision making, household decision-making, and women's mobility. Two measures were created for each dimension, and for the overall empowerment: women's independent decisions, and those taken jointly by couples. Contraceptive use was categorized as either female-only or couple methods on the basis of whether a method requires the awareness of, or some support and cooperation from, the husband. Multinomial regression was used, by means of Odds Ratios (OR), to assess associations between empowerment dimensions and female-only and couple contraceptive methods. RESULTS: Overall, women tend to get higher decision-making power with increased age, higher literacy, a greater number of children, or being in a household that has superior socio-economic status. The measures for couples' decision-making for overall empowerment and for each dimension of it showed positive associations with couple methods as well as with female-only methods. The only exception was the measure of economic empowerment, which was associated only with the couple method. CONCLUSION: Couples' joint decision-making is a stronger determinant of the use of contraceptive methods than women-only decision-making. This is the case over and above the contribution of women's socio-demographic and economic statuses. Effort needs to be made to educate women and their husbands equally, with particular focus on highly effective contraceptive methods. PMID- 25119726 TI - Simultaneous measurement of smoothened entry into and exit from the primary cilium. AB - Ciliary accumulation of signaling proteins must result from a rate of ciliary entry that exceeds ciliary exit, but approaches for distinguishing ciliary entry vs. exit are lacking. Using a photoconvertible fluorescent protein tag, we establish an assay that allows a separate but simultaneous examination of ciliary entry and exit of the Hedgehog signaling protein Smoothened in individual cells. We show that KAAD-cyclopamine selectively blocks entry, whereas ciliobrevin interferes initially with exit and eventually with both entry and exit of ciliary Smoothened. Our study provides an approach to understanding regulation of ciliary entry vs. exit of Hedgehog signaling components as well as other ciliary proteins. PMID- 25119729 TI - Peer influences on internalizing and externalizing problems among adolescents: a longitudinal social network analysis. AB - Adolescents who like each other may become more similar to each other with regard to internalizing and externalizing problems, though it is not yet clear which social mechanisms explain these similarities. In this longitudinal study, we analyzed four mechanisms that may explain similarity in adolescent peer networks with regard to externalizing and internalizing problems: selection, socialization, avoidance and withdrawal. At three moments during one school-year, we asked 542 adolescents (8th grade, M-age = 13.3 years, 51 % female) to report who they liked in their classroom, and their own internalizing and externalizing problems. Adolescents tend to prefer peers who have similar externalizing problem scores, but no significant selection effect was found for internalizing problems. Adolescents who share the same group of friends socialize each other and then become more similar with respect to externalizing problems, but not with respect to internalizing problems. We found no significant effects for avoidance or withdrawal. Adolescents may choose to belong to a peer group that is similar to them in terms of externalizing problem behaviors, and through peer group socialization (e.g., enticing, modelling, mimicking, and peer pressure) become more similar to that group over time. PMID- 25119730 TI - The effect of seasonality on the structure of rotifers in a black-water shallow lake in Central Amazonia. AB - Rotifers have often been used as indicators of sudden changes in physical and chemical features of the aquatic environment. Such features vary greatly during flood pulse events in small lakes connected to major floodplains. However, few are the studies that investigate the consequences of the flood pulse in rotifer species composition, abundance, richness and diversity, especially in Amazonian lakes. We analyzed samples from a small blackwater lake of an "igarape" connected permanently to the Negro river, in Central Amazonia. Samples were taken twice a year for two years, comprising flooding and receding periods of the flood pulse. Rotifer abundance increased significantly after draught events, and electrical conductivity and turbidity were intrinsically related to such variation. Species composition also changed from flooding to receding periods. Some taxa, such as Brachionus zahniseri reductus and Lecane remanei were restricted to receding periods, while Brachionus zahniseri, Brachionus gillardi and Lecane proiecta were only present during flooding. A shift in the composition of rotifer families was observed from one period to another, showing the effect of renewing waters of the flood pulse. These results suggest that the flood pulse acts as a driving force and stressing condition, considerably altering rotifer community dynamics, either changing species composition or decreasing abundance. PMID- 25119731 TI - Reproduction of a whiptail lizard (Ameivula ocellifera, Teiidae) from a coastal area in northeastern Brazil. AB - The reproductive ecology of Ameivula ocellifera was studied from September 2009 to August 2010 in a coastal area of the state of Ceara, Brazil. Females reproduced continuously throughout the year, with a peak at the end of the rainy season. Even though there was a predominance of pre-reproductive individuals in the sample, gonadal activity of males peaked synchronously to female reproduction. Mean clutch size was 1.98 +/- 0.56 and positively associated with female body size, while mean egg volume was 510.54 +/- 84.29 mm3 and unrelated to female body size. We did not find any association between clutch size and average egg volume. PMID- 25119733 TI - Richness, composition and trophic groups of an avian community in the Pernambuco Endemism Centre, Alagoas, Brazil. AB - In northeastern Brazil, the reduction of the natural forest cover to a series of small, isolated fragments has had negative consequences for the local avian fauna, in particular, a loss of the more specialized species, while the populations of some generalists have tended to increase. The present study focuses on the composition and trophic groups of a bird community on a farm in the northeastern Brazilian state of Alagoas. Monthly surveys were conducted between November 2008 and October 2009, based on mist-netting and systematic observations. Overall, 112 species were recorded, of which 76 were associated with the two forest fragments surveyed, while all the others were observed exclusively in the surrounding matrix of pasture and orchards. The bird community presented a predominance of insectivorous species, followed by omnivores. However, specialized trunk-creeping and understory insectivores accounted for only around 15% of the species in this feeding category. The reduced diversity of other guilds and species with more specialized diets, and the complete absence of sensitive species such as large parrots and raptors, reflects the severe fragmentation and degradation of the local forests, which has greatly reduced the availability of dietary resources and breeding sites. PMID- 25119732 TI - Bark harvesting systems of Drimys brasiliensis Miers in the Brazilian Atlantic rainforest. AB - Drimys brasiliensis Miers, locally known as cataia or casca-de-anta, is a native tree species of the Atlantic Rainforest. Its bark is harvested from natural populations. This study examined the recovery capacity of the bark of D. brasiliensis under different bark harvesting methods, as well as the influence of these approaches on its population dynamics and reproductive biology. While none of these treatments resulted in changes in phenological behavior or the rate of increase of diameter at breast height and tree height, the removal of wider bark strips resulted in lower rates of bark recovery and higher rates of insect attack and diseases. Accordingly, the results recommend using strips of bark 2 cm wide and 2 m long, with 4 cm between strips, for effective rates of bark regrowth and for lower susceptibility to insect attack and diseases. From these studies, we concluded that D. brasiliensis has a high potential for sustainable management of its natural populations, demonstrating the possibility of generating an important supplementary income for farmers and contributing to the use and conservation of the Atlantic Rainforest. PMID- 25119734 TI - Feeding and larval growth of an exotic freshwater prawn Macrobrachium equidens (Decapoda: Palaemonidae), from Northeastern Para, Amazon Region. AB - In the present study, we carried out experiments on the diet of the freshwater prawn Macrobrachium equidens. We tested which type of food and which density of food is suitable for larval development. For the experiment on the type of food, eight treatments were carried out: (I) starvation, (AL) microalgae, (RO) rotifers, (AN) Artemia, (RO + AN) rotifers + Artemia, (AL + RO) microalgae + rotifers, (AL + AN) microalgae + Artemia, (AL + RO + AN) microalgae + rotifers + Artemia. For the experiment on the density of food, we used the type of food, which had resulted in a high survival rate in the previous experiment. Three treatments were carried out: 4, 8 and 16 Artemia nauplii /mL. The rate of feeding during larval development was observed. The survival, weight and percentage of juveniles of each feeding experiment were determined. We found that larvae are carnivores; however, they have requirements with respect to the type of food, because larvae completed their cycle from the zoeal to the juvenile stage only when Artemia nauplii were available. We also verified that the larvae feed mainly during the day-time, and are opportunistic with respect to the density of food offered. PMID- 25119735 TI - Regulation of IL-8 promoter activity by verrucarin A in human monocytic THP-1 cells. AB - Macrocyclic trichothecenes have been frequently detected in fungi in water damaged buildings and exhibited higher toxicity than the well-studied trichothecenes; however, the mechanism underlying their toxicity has been poorly understood. In this study, transcriptional regulation of the cytokine interleukin (IL)-8 by a macrocyclic trichothecene, verrucarin A (VA), in human monocytic THP 1 cells is reported. Consistent with previous findings, VA was 100-fold more cytotoxic than deoxynivalenol (DON), while ochratoxin A (OA) was not cytotoxic. In cells transduced with the wild-type IL-8 promoter luciferase construct, VA induced a biphasic dose response composed of an upregulation of luciferase expression at low concentrations of 0.01-1 ng/ml and a downregulation at high levels of 10 ng/ml and higher. In contrast, DON induced a sigmoid-shaped dose response with the EC50 of 11.6 ng/ml, while OA did not markedly affect the IL-8 expression. When cells were transduced with IL-8 promoter with a mutation of transcription factor nuclear factor-kappaB (NF-kappaB)-binding site, VA (1 ng/ml), DON (1000 ng/ml), and tumor necrosis factor (TNF) alpha (20 ng/ml) induced luciferase expression were impaired. In addition, the NF-kappaB inhibitor caffeic acid phenethyl ester inhibited VA-, DON-, and TNFalpha-induced luciferase expression. Mutation of the CCAAT/enhancer-binding protein (CEBP) beta binding site of the IL-8 promoter affected only DON-, but not VA- and TNFalpha-induced luciferase expression. Taken together, these results suggested that VA activated IL-8 promoter via an NF-kappaB-dependent, but not CEBPbeta-dependent, pathway in human monocytes. PMID- 25119736 TI - Single-wall carbon nanotubes (SWCNT) induce cytotoxicity and genotoxicity produced by reactive oxygen species (ROS) generation in phytohemagglutinin (PHA) stimulated male human peripheral blood lymphocytes. AB - Single-wall carbon nanotubes (SWCNT) possess a small size, large surface area, and high reactivity, which enable them to permeate the cytoplasmic or nuclear membrane and attach to biological molecules. During medical applications, SWNCT are usually administered intravenously, which enhances interaction with blood components. Yet despite this exposure potential, safety evaluation studies of SWCNTs focused on human blood cells are still lacking. Therefore, this study was undertaken to examine cytotoxicity, genotoxicity, and proinflammatory responses following SWCNT treatment of phytohemagglutinin (PHA)-stimulated male human peripheral blood lymphocytes (PBL). SWCNT were found to inhibit cell growth, as well as to induce DNA breakage, and micronuclei (MN) formation via reactive oxygen species (ROS) generation. The addition of N-acetylcysteine (NAC) a cell permeable antioxidant, decreased ROS generation, cytotoxicity, and genotoxicity produced by SWCNT treatment. In addition, SWCNT induced tumor necrosis factor (TNF)-alpha release after 24 h, yet this phenomenon was not related to ROS generation, as antioxidant NAC treatment did not affect increased proinflammatory cytokine levels in the phytohemagglutinin (PHA)-stimulated male human PBL. PMID- 25119737 TI - Relationship between hemorrhagic stroke hospitalization and exposure to fine particulate air pollution in Taipei, Taiwan. AB - This study was undertaken to determine whether there was a correlation between fine particle (PM2.5) levels and hospital admissions for hemorrhagic stroke (HS) in Taipei, Taiwan. Hospital admissions for HS and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased HS admissions were significantly associated with PM2.5 levels both on warm days (>23 degrees C) and cool days (<23 degrees C), with an interquartile range rise associated with a 12% (95% CI = 7-18%) and 4% (95% CI = 0-8%) elevation in admissions for HS, respectively. In the two-pollutant models, PM2.5 remained significantly high after inclusion of SO2 or O3 on both warm and cool days. This study provides evidence that higher levels of PM2.5 increase the risk of hospital admissions for HS. PMID- 25119738 TI - The effect of composition, size, and solubility on acute pulmonary injury in rats following exposure to Mexico city ambient particulate matter samples. AB - Particulate matter (PM)-associated metals can contribute to adverse cardiopulmonary effects following exposure to air pollution. The aim of this study was to investigate how variation in the composition and size of ambient PM collected from two distinct regions in Mexico City relates to toxicity differences. Male Wistar Kyoto rats (14 wk) were intratracheally instilled with chemically characterized PM10 and PM2.5 from the north and PM10 from the south of Mexico City (3 mg/kg). Both water-soluble and acid-leachable fractions contained several metals, with levels generally higher in PM10 South. The insoluble and total, but not soluble, fractions of all PM induced pulmonary damage that was indicated by significant increases in neutrophilic inflammation, and several lung injury biomarkers including total protein, albumin, lactate dehydrogenase activity, and gamma-glutamyl transferase activity 24 and 72 h postexposure. PM10 North and PM2.5 North also significantly decreased levels of the antioxidant ascorbic acid. Elevation in lung mRNA biomarkers of inflammation (tumor necrosis factor [TNF]-alpha and macrophage inflammatory protein [MIP]-2), oxidative stress (heme oxygenase [HO]-1, lectin-like oxidized low-density lipoprotein receptor [LOX]-1, and inducibile nitric oxide synthase [iNOS]), and thrombosis (tissue factor [TF] and plasminogen activator inhibitor [PAI]-1), as well as reduced levels of fibrinolytic protein tissue plasminogen activator (tPA), further indicated pulmonary injury following PM exposure. These responses were more pronounced with PM10 South (PM10 South > PM10 North > PM2.5 North), which contained higher levels of redox-active transition metals that may have contributed to specific differences in selected lung gene markers. These findings provide evidence that surface chemistry of the PM core and not the water-soluble fraction played an important role in regulating in vivo pulmonary toxicity responses to Mexico City PM. PMID- 25119739 TI - Toxicity and accumulation of trinitrotoluene (TNT) and its metabolites in Atlantic salmon alevins exposed to an industrially polluted water. AB - A pond in an industrial area in Sweden was selected to study adverse effects on salmon alevins from 2,4,6-trinitrotoluene (TNT)-contaminated water. Chemical screening revealed heavy contamination of TNT and its degradation products, 2 amino-4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT), ranging from 0.05 to 230 g/kg in the sediment (dry weight) within the water system. Pond water contained 3 mg/L TNT. A dilution series of pond water mixed with tap water revealed increased death frequency in alevins down to fivefold dilution (approximate 0.4 mg TNT/L). Uptake was concentration dependent, reaching 7, 9, and 22 MUg/g tissue for TNT, 2-ADNT, and 4-ADNT at the highest test concentration. A time-dependent uptake of TNT and its degradation products was found at a water concentration of 0.08 mg TNT/L. Degradation products of TNT showed a more efficient uptake compared to native TNT, and accumulation of 4-ADNT was more pronounced during the late phase of the 40-d exposure study. Bioconcentration factors (BCF) (0.34, 52, and 134 ml/g for TNT, 2-ADNT, and 4 ADNT, respectively) demonstrated a significant uptake of the metabolite 4-ADNT in alevin tissue. Disturbed physiological conditions and delayed development in alevins were not studied, but may not be excluded even at 125-fold diluted pond water (0.016 mg TNT/L). BCF data indicated that bioaccumulation of TNT metabolites need to be considered in TNT chronic toxicity. Fish species and age differences in the accumulation of TNT metabolites need to be further studied. PMID- 25119741 TI - Identification of angiogenesis-related miRNAs in a population of patients with renal clear cell carcinoma. AB - In the present study, we compared the expression of miRNAs and angiogenesis related genes in the renal tumors and adjacent normal renal tissues of patients with clear cell renal cell carcinoma (ccRCC). The first part of the present study was a preliminary analysis of 4 patients with stage T1a/b ccRCC that measured the levels of angiogenesis and expression of angiogenesis-related genes and miRNAs in the tumors and adjacent normal renal tissues. The second part of this study was an analysis of 30 patients with stage T1, T2 or T3 ccRCC that employed qPCR to characterize expression of angiogenesis-related miRNAs in the tumors and adjacent normal tissues. The first part of this study indicated that all 4 patients had increased levels of CD34 in tumors, indicating elevated angiogenesis. However, quantitative analysis of microvessel density and expression of miRNAs indicated highly variable results among these patients. The data of all patients in the present study indicated that more patients with stage T1 ccRCC had higher expression of miR-126 and miR-378 in their normal tissues, whereas more patients with stage T2/3 ccRCC had higher expression of these miRNAs in their tumor tissues. The tumors of patients with ccRCC had lower expression of miR-126 and miR-378 during the early stages of disease (T1), but higher expression of these miRNAs during the later stages of disease (T2/T3). PMID- 25119742 TI - MicroRNA-193b is a regulator of amyloid precursor protein in the blood and cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's disease. AB - Amyloid precursor protein (APP) has an important function in the generation of Alzheimer's disease (AD). In our previous study, miR-193b was found to be downregulated in the hippocampi of 9-month-old APP/PS1 double-transgenic mice using microRNA (miR) array. In the present study, bioinformatic analyses showed that miR-193b was a miR that was predicted to potentially target the 3' untranslated region (UTR) of APP. Subsequently, the function of miR-193b on APP was studied. The levels of miR-193b, exosomal miR-193b, Abeta, tau, p-tau, HCY and APOE in samples from APP/PS1 double-transgenic mice, mild cognitive impairment (MCI) and dementia of Alzheimer-type (DAT) patients, were measured. The results indicated that overexpression of miR-193b could repress the mRNA and protein expression of APP. The miR-193b inhibitor oligonucleotide induced upregulation of APP. Binding sites of miR-193b in the 3'-UTR of APP were identified by luciferase assay. MCI and DAT patients had lower exosomal miR-193b, but not total miR-193b, in the blood as compared with the controls. DAT patients had lower exosomal miR-193b levels in blood as compared with the MCI group. A decreased exosomal miR-193b expression level was additionally observed in the cerebral spinal fluid (CSF) of DAT patients. Negative correlations were found between exosomal miR-193b and Abeta42 in the CSF of DAT patients. In conclusion, these findings showed that miR-193b may function in the development of AD and exosomal miR-193b has potential as a novel, non-invasive, blood-based biomarker of MCI and DAT patients. PMID- 25119743 TI - Immunoprophylaxis against respiratory syncytial virus with palvizumab: what is new? PMID- 25119744 TI - Respiratory infections in children up to two years of age on prophylaxis with palivizumab. AB - OBJECTIVE: To identify the viruses involved in acute respiratory tract infections and to analyze the rates of hospitalization and death in children on palivizumab prophylaxis. METHODS: Prospective cohort of 198 infants up to one year old who were born before 29 weeks of gestational age and infants under two years old with hemodynamically unstable cardiopathy or chronic pulmonary disease who received prophylactic palivizumab against severe respiratory syncytial virus infections in 2008. During the study period, in each episode of acute respiratory tract infection, nasopharyngeal aspirate was collected to identify respiratory syncytial virus, adenovirus, parainfluenza 1, 2 and 3, influenza A and B by direct immunofluorescence, rhinovirus and metapneumovirus by polymerase chain reaction preceded by reverse transcription. Data regarding hospitalization and deaths were monitored. RESULTS: Among the 198 studied infants, 117 (59.1%) presented acute respiratory tract infections, with a total of 175 episodes. Of the 76 nasopharyngeal aspirates collected during respiratory tract infections, 37 were positive, as follow: rhinovirus (75.7%), respiratory syncytial virus (18.9%), parainfluenza (8.1%), adenovirus 2 (2.7%), metapneumovirus (2.7%) and three samples presented multiple agents. Of the 198 children, 48 (24.4%) were hospitalized: 30 (15.2%) for non-infectious etiology and 18 (9.1%) for respiratory causes. Among these 18 children, one case of respiratory syncytial virus was identified. Two deaths were reported, but respiratory syncytial virus was not identified. CONCLUSIONS: During the prophylaxis period, low frequency of respiratory syncytial virus infections and low rates of hospitalization were observed, suggesting the benefit of palivizumab prophylaxis. PMID- 25119745 TI - Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service. AB - OBJECTIVE: To determine the frequence and profile of congenital heart defects in Down syndrome patients referred to a pediatric cardiologic center, considering the age of referral, gender, type of heart disease diagnosed by transthoracic echocardiography and its association with pulmonary hypertension at the initial diagnosis. METHODS: Cross-sectional study with retrospective data collection of 138 patients with Down syndrome from a total of 17,873 records. Descriptive analysis of the data was performed, using Epi-Info version 7. RESULTS: Among the 138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were diagnosed with congenital heart disease. The most common lesion was ostium secundum atrial septal defect, present in 51.8%, followed by atrioventricular septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the heart diseases. Only 35.5% of the patients were referred before six months of age. CONCLUSIONS: The low percentage of referral until six months of age highlights the need for a better tracking of patients with Down syndrome in the context of congenital heart disease, due to the high frequency and progression of pulmonary hypertension. PMID- 25119746 TI - Estimating outcomes in newborn infants using fuzzy logic. AB - OBJECTIVE: To build a linguistic model using the properties of fuzzy logic to estimate the risk of death of neonates admitted to a Neonatal Intensive Care Unit. METHODS: Computational model using fuzzy logic. The input variables of the model were birth weight, gestational age, 5th-minute Apgar score and inspired fraction of oxygen in newborn infants admitted to a Neonatal Intensive Care Unit of Taubate, Southeast Brazil. The output variable was the risk of death, estimated as a percentage. Three membership functions related to birth weight, gestational age and 5th-minute Apgar score were built, as well as two functions related to the inspired fraction of oxygen; the risk presented five membership functions. The model was developed using the Mandani inference by means of Matlab(r) software. The model values were compared with those provided by experts and their performance was estimated by ROC curve. RESULTS: 100 newborns were included, and eight of them died. The model estimated an average possibility of death of 49.7+/-29.3%, and the possibility of hospital discharge was 24+/-17.5%. These values are different when compared by Student's t-test (p<0.001). The correlation test revealed r=0.80 and the performance of the model was 81.9%. CONCLUSIONS: This predictive, non-invasive and low cost model showed a good accuracy and can be applied in neonatal care, given the easiness of its use. PMID- 25119747 TI - Preterm newborns at Kangaroo Mother Care: a cohort follow-up from birth to six months. AB - OBJECTIVE: To evaluate clinical outcomes, growth and exclusive breastfeeding rates in premature infants assisted by Kangaroo Mother Care at birth, at discharge and at six months of life. METHODS: Prospective study of a premature infants cohort assisted by Kangaroo Mother Care in a tertiary public maternity in Northeast Brazil with birth weight <=1750g and with clinical conditions for Kangaroo care. RESULTS: The sample was composed by 137 premature infants, being 62.8% female, with average birth weight of 1365+/-283g, average gestational age of 32+/-3 weeks and 26.2% were adequate for gestational age. They have been admitted in the Kangaroo Ward with a median of 13 days of life, weighing 1430+/ 167g and, at this time, 57.7% were classified as small for corrected gestational age. They were discharged with 36.8+/-21.8 days of chronological age, weighing 1780+/-165g and 67.9% were small for corrected gestational age. At six months of life (n=76), they had an average weight of 5954+/-971g, and 68.4% presented corrected weight for gestational age between percentiles 15 and 85 of the World Health Organization (WHO) weight curve. Exclusive breastfeeding rate at discharge was 56.2% and, at six months of life, 14.4%. CONCLUSIONS: In the studied sample, almost two thirds of the children assisted by Kangaroo Mother Care were, at six months of life, between percentiles 15 and 85 of the WHO weight curves. The frequency of exclusive breastfeeding at six months was low. PMID- 25119748 TI - Alpha-tocopherol concentration in serum and colostrum of mothers with gestational diabetes mellitus. AB - OBJECTIVE: To evaluate and compare the levels of alpha-tocopherol in colostrum and in the serum of healthy and diabetic mothers. METHODS: This cross-sectional study enrolled 51 volunteer mothers, 20 with the diagnosis of gestational diabetes mellitus and 31 without associated diseases. Serum and colostrum samples were collected in fasting in the immediate postpartum period and alpha-tocopherol was analyzed by high performance liquid chromatography (HPLC). In order to define the nutritional status of vitamin E, the cutoff point for the serum (697.7ug/dL) was adopted. Student's t-test for independent variables compared the average concentrations of alpha-tocopherol in the serum and in the colostrum between control and gestational diabetes mellitus groups. Pearson's correlation was used to assess the relationship between the concentration of alpha-tocopherol in serum and colostrum for both groups. Differences were considered significant when p<0.05. RESULTS: The alpha-tocopherol concentration in colostrum was 1,483.1+/ 533.8ug/dL for Control Group and 1,368.8+/-681.8ug/dL for diabetic women, without differences between groups (p=0.50). However, alpha-tocopherol concentration in the serum was 1,059.5+/-372.7ug/dL in the Control Group and 1,391.4+/-531.5ug/dL in the diabetic one (p<0.01). No correlation was found between the concentration of alpha-tocopherol in the serum and in the colostrum for control and diabetic groups. CONCLUSIONS: The groups had adequate nutritional status of vitamin E. Gestational diabetes was not associated with changes in alpha-tocopherol concentration in colostrum. PMID- 25119749 TI - Pediatrician's knowledge on the management of the infant who cries excessively in the first months of life. AB - OBJECTIVE: To evaluate the attitude, the practice and the knowledge of pediatricians regarding the management of the infant who cries excessively in the first months of life. METHODS: Descriptive cross-sectional study that enrolled pediatricians (n=132) randomly interviewed at a Pediatric meeting in Brazil, in August 2012. The data were collected by a self-administered standardized form after reading the hypothetical case of an infant who cried excessively. RESULTS: The majority of the participants were females, the mean age was 39 years and the average mean time working in the specialty was 14 years; 52.2% were Board Certified by the Brazilian Society of Pediatrics. The diagnosis most often considered was gastroesophageal reflux disease (62.9%), followed by infant colic (23.5%) and cow's milk allergy (6.8%). The diagnostic test most frequently mentioned was 24-hour esophageal pH-monitoring (21.9%). The medications most frequently indicated were domperidone (30.3%), the combination of domperidone with ranitidine (12.1%) and paracetamol (6%). CONCLUSIONS: In the approach of the infant who cries excessively, diagnostic tests are frequently requested and unnecessary medical treatment is usually recommended. PMID- 25119750 TI - Intake of protein, calcium and sodium in public child day care centers. AB - OBJECTIVE: To assess calcium, protein and sodium intake, of children that attend public day-care centers and to compare it with the recommended one. METHODS: Cross-sectional descriptive study in seven public day care centers of Sao Paulo city, Southeast Brazil, which enrolled 366 children between 12 and 36 months of age. The data collection occurred between September and December 2010. Each day care center was evaluated for three non-consecutive days, totaling 42 days and 210 meals. Dietary intake was assessed by a direct food weighing method. For the nutritional calculation, DietWin(r) Profissional 2.0 was used, and the adequacy was calculated according to the recommendations of the National School Feeding Program for energy, protein, calcium and sodium. The calcium/protein relation was also calculated, as well as calcium density (mg/1,000kcal). RESULTS: The energy (406.4kcal), protein (18.2g) and calcium (207.6mg) consumption did not reach the recommended values in all the evaluated day care centers. Sodium intake exceeded up to three times the recommendation. The calcium/protein ratio of 11.7mg/g was less than the adequate one (20mg/g). CONCLUSIONS: There was inadequacy of calcium, protein and sodium dietary intake, in children attending public day-care centers. PMID- 25119751 TI - Prevalence of weight excess according to age group in students from Campinas, SP, Brazil. AB - OBJECTIVE: To evaluate the prevalence of weight excess in children and adolescents attending public and private schools of Campinas, Southeast Brazil, according to age group. METHODS: Cross-sectional study that enrolled 3,130 students from 2010 to 2012. The weight and the height were measured and the body mass index (BMI) was calculated. The students were classified by BMI Z-score/age curves of the World Health Organization (WHO)-2007 (thinness, normal weight, overweight and obesity) and by age group (7-10, 11-14 and 15-18 years). Multinomial logistic regression analysis was applied to verify variables associated to overweight and obesity. RESULTS: Among the 3,130 students, 53.7% attended public schools and 53.4% were girls. The prevalence of weight excess (overweight or obesity) was higher in private schools (37.3%) than in public ones (32.9%) and among males (37.5%), compared to females (32.7%; p<0.05). The chance of having weight excess in children aged 7-10 years was more than twice of those over 15 years old (OR 2.4; 95%CI 2.0-3.0) and it was 60% higher for the group with 11-14 years old (OR 1.6; 95%CI 1.3-2.0). The chance of being obese was three times higher in 7-10 years old children than in the adolescents with 15-18 years old (OR 4.4; 95%CI 3.3-6.4) and 130% higher than the group with 11-14 years old (OR 2.3; 95%CI 1.6-3.2). CONCLUSIONS: The prevalence of weight excess in Campinas keeps increasing at an alarming rate, especially in the younger age group. PMID- 25119752 TI - Body composition and risk for metabolic alterations in female adolescents. AB - OBJECTIVE: To study anthropometrical and body composition variables as predictors of risk for metabolic alterations and metabolic syndrome in female adolescents. METHODS: Biochemical, clinical and corporal composition data of 100 adolescents from 14 to 17 years old, who attended public schools in Vicosa, Southeastern Brazil, were collected. RESULTS: Regarding nutritional status, 83, 11 and 6% showed eutrophia, overweight/obesity and low weight, respectively, and 61% presented high body fat percent. Total cholesterol presented the highest percentage of inadequacy (57%), followed by high-density lipoprotein (HDL - 50%), low-density lipoprotein (LDL - 47%) and triacylglycerol (22%). Inadequacy was observed in 11, 9, 3 and 4% in relation to insulin resistance, fasting insulin, blood pressure and glycemia, respectively. The highest values of the fasting insulin and the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) were verified at the highest quartiles of body mass index (BMI), waist perimeter, waist-to-height ratio and body fat percent. Body mass index, waist perimeter, and waist-to-height ratio were the better predictors for high levels of HOMA-IR, blood glucose and fasting insulin. Waist-to-hip ratio was associated to arterial hypertension diagnosis. All body composition variables were effective in metabolic syndrome diagnosis. CONCLUSIONS: Waist perimeter, BMI and waist-to height ratio showed to be good predictors for metabolic alterations in female adolescents and then should be used together for the nutritional assessment in this age range. PMID- 25119753 TI - Assessment of calcium intake by adolescents. AB - OBJECTIVE: To evaluate the daily calcium intake of adolescents in schools from Chapeco, Santa Catarina, Southern Brazil, to check if calcium intake is in accordance with the Dietary Reference Intakes (DRI), and to investigate variables associated with daily calcium intake. METHODS: Cross-sectional study approved by the Institutional Review Board and developed in 2010. Students of the 8th grade completed questionnaires with personal data and questions about the calcium-rich foods intake frequency. In order to compare students with adequate (1300mg) or inadequate intake of calcium/day (<1300mg), parametric and nonparametric tests were used. RESULTS: A total of 214 students with a mean age of 14.3+/-1.0 years were enrolled. The median daily calcium intake was 540mg (interquartile range - IQ: 312-829mg) and only 25 students (11.7%) had calcium intake within the recommendations of the DRI for age. Soft drink consumption >=3 times/week was associated with a lower intake of calcium. CONCLUSIONS: Few students ingested adequate levels of calcium for the age group. It is necessary to develop a program to encourage a greater intake of calcium-rich foods in adolescence. PMID- 25119754 TI - Neck circumference as a new anthropometric indicator for prediction of insulin resistance and components of metabolic syndrome in adolescents: Brazilian Metabolic Syndrome Study. AB - OBJECTIVE: To evaluate the correlation between neck circumference and insulin resistance and components of metabolic syndrome in adolescents with different adiposity levels and pubertal stages, as well as to determine the usefulness of neck circumference to predict insulin resistance in adolescents. METHODS: Cross sectional study with 388 adolescents of both genders from ten to 19 years old. The adolescents underwent anthropometric and body composition assessment, including neck and waist circumferences, and biochemical evaluation. The pubertal stage was obtained by self-assessment, and the blood pressure, by auscultation. Insulin resistance was evaluated by the Homeostasis Model Assessment-Insulin Resistance. The correlation between two variables was evaluated by partial correlation coefficient adjusted for the percentage of body fat and pubertal stage. The performance of neck circumference to identify insulin resistance was tested by Receiver Operating Characteristic Curve. RESULTS: After the adjustment for percentage body fat and pubertal stage, neck circumference correlated with waist circumference, blood pressure, triglycerides and markers of insulin resistance in both genders. CONCLUSIONS: The results showed that the neck circumference is a useful tool for the detection of insulin resistance and changes in the indicators of metabolic syndrome in adolescents. The easiness of application and low cost of this measure may allow its use in Public Health services. PMID- 25119755 TI - Biochemical, anthropometric and body composition indicators as predictors of hepatic steatosis in obese adolescents. AB - OBJECTIVE: To describe the prevalence of hepatic steatosis and to assess the performance of biochemical, anthropometric and body composition indicators for hepatic steatosis in obese teenagers. METHODS: Cross-sectional study including 79 adolecents aged from ten to 18 years old. Hepatic steatosis was diagnosed by abdominal ultrasound in case of moderate or intense hepatorenal contrast and/or a difference in the histogram >=7 on the right kidney cortex. The insulin resistance was determined by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index for values >3.16. Anthropometric and body composition indicators consisted of body mass index, body fat percentage, abdominal circumference and subcutaneous fat. Fasting glycemia and insulin, lipid profile and hepatic enzymes, such as aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase, were also evaluated. In order to assess the performance of these indicators in the diagnosis of hepatic steatosis in teenagers, a ROC curve analysis was applied. RESULTS: Hepatic steatosis was found in 20% of the patients and insulin resistance, in 29%. Gamma glutamyltransferase and HOMA-IR were good indicators for predicting hepatic steatosis, with a cutoff of 1.06 times above the reference value for gamma glutamyltransferase and 3.28 times for the HOMA-IR. The anthropometric indicators, the body fat percentage, the lipid profile, the glycemia and the aspartate aminotransferase did not present significant associations. CONCLUSIONS: Patients with high gamma-glutamyltransferase level and/or HOMA-IR should be submitted to abdominal ultrasound examination due to the increased chance of having hepatic steatosis. PMID- 25119756 TI - Associated factors of overweight in adolescents from public schools in Northern Minas Gerais State, Brazil. AB - OBJECTIVE: In order to support plans and actions that combat the local increasing overweight and obesity prevalence in adolescents, the factors associated to weight excess in public school students from Montes Claros, MG, Southeast Brazil, were studied. METHODS: Cross-sectional study with a sample of adolescents from the public schools of the city. The nutritional status was evaluated and an inquiry was carried out in the schools to determine food consumption and practice of physical activities. Factors associated to weight excess were assessed by bivariate analysis followed by logistic regression. RESULTS: Weight excess prevalence was detected in 18.5% of the 535 adolescents evaluated. The factors associated to weight excess were: per capita income above half minimum wage (OR 1.99; 95%CI 1.01-3.93), candy consumption above two daily portions (OR 1.94; 95%CI 1.13-3.32) and absence of sport activity during leisure time (OR 2.54; 95%CI 1.15-5.59). CONCLUSIONS: The proportion of weight excess in adolescents from public schools is relevant and associated with socioeconomic condition of the family, bad eating habits and sedentary life. PMID- 25119757 TI - Cardiac autonomic dysfunction in obese normotensive children and adolescents. AB - OBJECTIVE: To test the hypothesis that obese normotensive children and adolescents present impaired cardiac autonomic control compared to non-obese normotensive ones. METHODS: For this cross-sectional study, 66 children and adolescents were divided into the following groups: Obese (n=31, 12+/-3 years old) and Non-Obese (n=35, 13+/-3 years old). Obesity was defined as body mass index greater than the 95th percentile for age and gender. Blood pressure was measured by oscillometric method after 15 minutes of rest in supine position. The heart rate was continuously registered during ten minutes in the supine position with spontaneous breathing. The cardiac autonomic control was assessed by heart rate variability, which was calculated from the five-minute minor variance of the signal. The derivations were the index that indicates the proportion of the number of times in which normal adjacent R-R intervals present differences >50 miliseconds (pNN50), for the time domain, and, for the spectral analysis, low (LF) and high frequency (HF) bands, besides the low and high frequencies ratio (LF/HF). The results were expressed as mean+/-standard deviation and compared by Student's t-test or Mann-Whitney's U-test. RESULTS: Systolic blood pressure (116+/-14 versus 114+/-13mmHg, p=0.693) and diastolic blood pressure (59+/-8 versus 60+/-11mmHg, p=0.458) were similar between the Obese and Non-Obese groups. The pNN50 index (29+/-21 versus 43+/-23, p=0.015) and HF band (54+/-20 versus 64+/-14 normalized units - n.u., p=0.023) were lower in the Obese Group. The LF band (46+/-20 versus 36+/-14 n.u., p=0.023) and LF/HF ratio (1.3+/-1.6 versus 0.7+/-0.4, p=0.044) were higher in Obese Group. CONCLUSIONS: Obese normotensive children and adolescents present impairment of cardiac autonomic control. PMID- 25119758 TI - Assessment of respiratory muscle strength in children according to the classification of body mass index. AB - OBJECTIVE: To assess and compare the respiratory muscle strength among eutrophic, overweight and obese school children, as well as to identify anthropometric and respiratory variables related to the results. METHODS: Cross-sectional survey with healthy schoolchildren aged 7-9 years old, divided into three groups: Normal weight, Overweight and Obese. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was applied. The body mass index (BMI) was evaluated, as well as the forced expiratory volume in one second (FEV1) with a portable digital device. The maximal inspiratory and expiratory pressures (MIP and MEP) were measured by a digital manometer. Comparisons between the groups were made by Kruskal-Wallis test. Spearman's correlation coefficient was used to analyze the correlations among the variables. RESULTS: MIP of eutrophic school children was higher than MIP found in overweight (p=0.043) and obese (p=0.013) children. MIP was correlated with BMI percentile and weight classification (r= 0.214 and r=-0.256) and MEP was correlated with height (r=0.328). Both pressures showed strong correlation with each other in all analyses (r>=0.773), and less correlation with FEV1 (MIP - r=0.362 and MEP - r=0.494). FEV1 correlated with MEP in all groups (r: 0.429 - 0.569) and with MIP in Obese Group (r=0.565). Age was correlated with FEV1 (r=0.578), MIP (r=0.281) and MEP (r=0.328). CONCLUSIONS: Overweight and obese children showed lower MIP values, compared to eutrophic ones. The findings point to the influence of anthropometric variables on respiratory muscle strength in children. PMID- 25119759 TI - Prevalence of headache and its interference in the activities of daily living in female adolescent students. AB - OBJECTIVE: To describe the prevalence of headache and its interference in the activities of daily living (ADL) in female adolescent students. METHODS: This descriptive cross-sectional study enrolled 228 female adolescents from a public school in the city of Petrolina, Pernambuco, Northeast Brazil, aged ten to 19 years. A self-administered structured questionnaire about socio-demographic characteristics, occurrence of headache and its characteristics was employed. Headaches were classified according to the International Headache Society criteria. The chi-square test was used to verify possible associations, being significant p<0.05. RESULTS: After the exclusion of 24 questionnaires that did not met the inclusion criteria, 204 questionnaires were analyzed. The mean age of the adolescents was 14.0+/-1.4 years. The prevalence of headache was 87.7%. Of the adolescents with headache, 0.5% presented migraine without pure menstrual aura; 6.7%, migraine without aura related to menstruation; 1.6%, non-menstrual migraine without aura; 11.7%, tension-type headache and 79.3%, other headaches. Significant associations were found between pain intensity and the following variables: absenteeism (p=0.001); interference in ADL (p<0.001); medication use (p<0.001); age (p=0.045) and seek for medical care (p<0.022). CONCLUSIONS: The prevalence of headache in female adolescents observed in this study was high, with a negative impact in ADL and school attendance. PMID- 25119760 TI - Congenital heart disease and chromossomopathies detected by the karyotype. AB - OBJECTIVE: To review the relationship between congenital heart defects and chromosomal abnormalities detected by the karyotype. DATA SOURCES: Scientific articles were searched in MEDLINE database, using the descriptors "karyotype" OR "chromosomal" OR "chromosome" AND "heart defects, congenital". The research was limited to articles published in English from 1980 on. DATA SYNTHESIS: Congenital heart disease is characterized by an etiologically heterogeneous and not well understood group of lesions. Several researchers have evaluated the presence of chromosomal abnormalities detected by the karyotype in patients with congenital heart disease. However, most of the articles were retrospective studies developed in Europe and only some of the studied patients had a karyotype exam. In this review, only one study was conducted in Latin America, in Brazil. It is known that chromosomal abnormalities are frequent, being present in about one in every ten patients with congenital heart disease. Among the karyotype alterations in these patients, the most important is the trisomy 21 (Down syndrome). These patients often have associated extra-cardiac malformations, with a higher risk of morbidity and mortality, which makes heart surgery even more risky. CONCLUSIONS: Despite all the progress made in recent decades in the field of cytogenetic, the karyotype remains an essential tool in order to evaluate patients with congenital heart disease. The detailed dysmorphological physical examination is of great importance to indicate the need of a karyotype. PMID- 25119761 TI - Tools used for evaluation of Brazilian children's quality of life. AB - OBJECTIVE: To review the available tools to evaluate children's quality of life validated for Brazilian language and culture. DATA SOURCES: Search of scientific articles in Medline, Lilacs and SciELO databases using the combination of descriptors "quality of life", "child" and "questionnaires" in Portuguese and English. DATA SYNTHESIS: Among the tools designed to assess children's quality of life validated for the Brazilian language and culture, the Auto questionnaire Qualite de Vie Enfant Image (AUQEI), the Child Health Questionnaire - Parent Form 50 (CHQ-PF50), the Pediatric Quality of Life Inventory (PedsQL(tm)) version 4.0 and the Kidscreen-52 are highlighted. Some tools do not include all range of ages and some lack domains that are currently considered relevant in the context of childhood, such as bullying. Moreover, due to the cultural diversity of Brazil, it may be necessary to adapt some instruments or to validate other tools. CONCLUSIONS: There are validated instruments to evaluate children's quality of life in Brazil. However, the validation or the adaptation of other international tools have to be considered in order to overcome current deficiencies. PMID- 25119762 TI - Heart rate variability in children with type 1 diabetes mellitus. AB - OBJECTIVE: To gather current information about the effects of type 1 diabetes mellitus on children's cardiac autonomic behavior. DATA SOURCES: The search of articles was conducted on PubMed, Ibecs, Medline, Cochrane, Lilacs, SciELO and PEDro databases using the MeSH terms: "autonomic nervous system", "diabetes mellitus", "child", "type 1 diabetes mellitus", "sympathetic nervous system" and "parasympathetic nervous system", and their respective versions in Portuguese (DeCS). Articles published from January 2003 to February 2013 that enrolled children with 9-12 years old with type 1 diabetes mellitus were included in the review. DATA SYNTHESIS: The electronic search resulted in four articles that approached the heart rate variability in children with type 1 diabetes mellitus, showing that, in general, these children present decreased global heart rate variability and vagal activity. The practice of physical activity promoted benefits for these individuals. CONCLUSIONS: Children with type 1 diabetes mellitus present changes on autonomic modulation, indicating the need for early attention to avoid future complications in this group. PMID- 25119764 TI - Let's reduce the blood volume collected for laboratorial exams? PMID- 25119763 TI - Genitalia burn: accident or violence? Concerns that transcend injury treatment. AB - OBJECTIVE: To describe a case of genital burn which raised the suspicion of maltreatment (sexual abuse and neglect by lack of supervision). CASE DESCRIPTION: An infant was taken to the Emergency Room of a pediatric hospital with an extensive burn in the vulva and perineum. The mother claimed the burn had been caused by a sodium-hydroxide-based product. However, the injury severity led to the suspicion of sexual abuse, which was then ruled out by a multidisciplinary team, based on the consistent report by the mother. Besides, the lesion type matched those caused by the chemical agent involved in the accident and the family context was evaluated and considered adequate. The patient had a favorable outcome and was discharged after four days of hospitalization. Outpatient follow up during six months after the accident enabled the team to rule out neglect by lack of supervision. COMMENTS: Accidents and violence are frequent causes of physical injuries in children, and the differential diagnosis between them can be a challenge for healthcare workers, especially in rare clinical conditions involving patients who cannot speak for themselves. The involvement of a multidisciplinary trained team helps to have an adequate approach, ensuring child protection and developing a bond with the family; the latter is essential for a continued patient follow-up. PMID- 25119775 TI - An organic hydrophilic dye for water-based dye-sensitized solar cells. AB - In this study we report the first organic hydrophilic dye employed for 100% water based electrolyte DSSCs. We show that the replacement of alkyl by glycolic chains in the dye structure is able to provide excellent wettability, resulting in an efficient system with remarkably reduced desorption problems that allowed us to perform tests over a wide pH range. By changing the electrolyte composition, employing chenodeoxycholic acid as a co-adsorbent and using PEDOT counter electrodes, 3% power conversion efficiency under 1-sun illumination was obtained. We show that chenodeoxycholic acid does not significantly increase the wettability, and we provide new insights into the higher performance resulting from its co-adsorption. PMID- 25119777 TI - Association Between Serum Amyloid-Beta and Renal Functions: Implications for Roles of Kidney in Amyloid-Beta Clearance. AB - Amyloid-beta (Abeta) plays a central role in the pathogenesis of Alzheimer's disease (AD), and it is a major therapeutic target for AD. It is proposed that removal of Abeta in blood can facilitate Abeta clearance from the brain, representing a promising therapeutic approach for AD. However, the efficacy and mechanisms for Abeta clearance by peripheral organs and tissues remain largely unknown. In the present study, 47 chronic kidney disease (CKD) patients (16 newly diagnosed patients who had never been dialyzed and 31 patients who were receiving dialysis) and 43 normal controls (NC) were enrolled. We found that serum Abeta levels were significantly higher in CKD patients than NC. CKD patients who were receiving dialysis had lower serum Abeta levels than patients without receiving dialysis, being comparable to NC. Furthermore, serum Abeta levels were correlated with renal functions reflected by estimated glomerular filtration rate (eGFR) and residual GFR (rGFR). Our study suggests that kidney is involved in peripheral clearance of Abeta, and dialysis might be a potential therapeutic approach of Abeta removal. PMID- 25119778 TI - The case for extracellular Nm23-H1 as a driver of acute myeloid leukaemia (AML) progression. AB - Studies in the 1990s identified a link between extracellular Nm23 proteins and acute myeloid leukaemia (AML). Confidence in the importance of these observations was undermined by a lack of appreciation that extracellular Nm23 proteins were relevant to either normal or pathophysiology coupled with the lack of demonstrable activity of Nm23 proteins against human AML cell lines. However, independent studies have highlighted the importance of Nm23-H1 in AML and have identified an elaborate Nm23-H1-mediated cross talk between cells within the AML clone. In other studies, roles for Nm23-H1 have now also been implicated in the maintenance of the stem cell state of embryonic stem (ES) cells and induced pluripotent stem (IPS) cells. In this review, we have generated a unifying model of the action of Nm23-H1 in AML, including previously unpublished data from our laboratory, and provide arguments as to why we consider this role to be distinct from that in ES and IPS cells. PMID- 25119780 TI - A Cross-sectional Analysis Investigating Organizational Factors That Influence Near-Miss Error Reporting Among Hospital Pharmacists. AB - OBJECTIVE: Underreporting near-miss errors undermines hospitals' ability to improve patient safety. The objective of this analysis was to determine the extent to which punitive work climate, inadequate error feedback to staff, or insufficient preventative procedures are associated with decreased frequency of near-miss error reporting among hospital pharmacists. METHODS: Survey data were obtained from the Agency of Healthcare Research and Quality 2010 Hospital Survey on Patient Safety Culture. Near-miss error reporting was defined using a Likert scale response to the question, "When a mistake is made, but is caught and corrected before affecting the patient, how often is this reported?" Work climate, error feedback to staff, and preventative procedures were defined similarly using responses to survey questions. Multivariate ordinal regressions estimated the likelihood of agreeing that near-miss errors were rarely reported, conditional upon perceived levels of punitive work climate, error feedback, or preventative procedures. RESULTS: Pharmacists disagreeing that procedures were sufficient and that feedback on errors was adequate were more likely to report that near-miss errors were rarely reported (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7-3.8; OR, 3.5; 95% CI, 2.5-5.1). Those agreeing that mistakes were held against them were equally likely as those disagreeing to report that errors were rarely reported (OR, 0.84; 95% CI, 0.61-1.1). CONCLUSIONS: Inadequate error feedback to staff and insufficient preventative procedures increase the likelihood that near-miss errors will be underreported. Hospitals seeking to improve near-miss error reporting should improve error-reporting infrastructures to enable feedback, which, in turn, would create a more preventative system that improves patient safety. PMID- 25119779 TI - Unique immunomodulatory effects of azelastine on dendritic cells in vitro. AB - Allergic contact dermatitis and atopic dermatitis are among the most common inflammatory skin diseases in western countries, and antigen-presenting cells like dendritic cells (DC) are key players in their pathophysiology. Histamine, an important mediator of allergic reactions, influences DC maturation and cytokine secretion, which led us to investigate the immunomodulatory potential of the well known histamine H1 receptor antagonists: azelastine, olopatadine, cetirizine, and pyrilamine. Unlike other H1 antihistamines, azelastine decreased lipopolysaccharide-induced tumor necrosis factor alpha and interleukin-12 secretion from murine bone marrow-derived DC. This effect was independent of histamine receptors H1, H2, or H4 and may be linked to inhibition of the nuclear factor kappa B pathway. Moreover, only azelastine reduced proliferation of allogenic T cells in a mixed leukocyte reaction. We then tested topical application of the H1 antihistamines on mice sensitized against toluene-2,4 diisocyanate, a model of Th2-mediated allergic contact dermatitis. In contrast to the in vitro results, all investigated substances were efficacious in reducing allergic ear swelling. Azelastine has unique effects on dendritic cells and T cell interaction in vitro. However, this did not translate into superior in vivo efficacy for Th2-mediated allergic dermatitis, possibly due to the effects of the antihistamines on other cell types involved in skin inflammation. Future research will have to clarify whether these properties are relevant to in vivo models of allergic inflammation with a different T cell polarization. PMID- 25119781 TI - Racial and Ethnic Disparities in Patient Safety. AB - BACKGROUND: Although there is extensive evidence on disparities in the process and outcomes of health care, data on racial and ethnic disparities in patient safety remain inconclusive in the United States. OBJECTIVES: The aims of this study were to (1) explore differences in reporting race/ethnicity in studies on disparities in patient safety; (2) assess adjustment for socioeconomic status, comorbidity, and disease severity; and (3) make recommendations on the inclusion of race/ethnicity for future studies on adverse events. METHODS: We searched PubMed database (for articles published from 1991 to May 1, 2013) using a predetermined criteria for studies on racial and ethnic disparities in patient safety. Only quantitative studies that used chart review or administrative data for the detection of adverse events were considered for eligibility. Two reviewers independently extracted data on inclusion of race/ethnicity in baseline characteristics and in stratification of outcomes. RESULTS: A total of 174 studies were initially obtained from the search. Of these, 24 met inclusion criteria and received full-text review. Meta-analysis was not performed because of the methodological and statistical heterogeneity between studies. Eight studies included race/ethnicity in baseline characteristics and adjusted for confounders. Hospital-level variations such teaching status and percentage of minorities served were infrequently analyzed. CONCLUSIONS: To our knowledge, this is the first methodological review of racial/ethnic disparities in patient safety in the United States. The evidence on the existence of disparities in adverse events was mixed. Poor stratification of outcomes by race/ethnicity and consideration of geographic and hospital-level variations explain the inconclusive evidence; variations in the quality of care at hospitals should be considered in studies using national databases. PMID- 25119776 TI - Mice Lacking Functional Fas Death Receptors Are Protected from Kainic Acid Induced Apoptosis in the Hippocampus. AB - The Fas receptor (FasR)/Fas ligand (FasL) system plays a significant role in the process of neuronal loss in neurological disorders. Thus, in the present study, we used a real-time PCR array focused apoptosis (Mouse Apoptosis RT(2) PCR Array) to study the role of the Fas pathway in the apoptotic process that occurs in a kainic acid (KA) mice experimental model. In fact, significant changes in the transcriptional activity of a total of 23 genes were found in the hippocampus of wild-type C57BL/6 mice after 12 h of KA treatment compared to untreated mice. Among the up-regulated genes, we found key factors involved in the extrinsic apoptotic pathway, such as tnf, fas and fasL, and also in caspase genes (caspase 4, caspase-8 and caspase-3). To discern the importance of the FasR/FasL pathway, mice lacking the functional Fas death receptor (lpr) were also treated with KA. After 24 h of neurotoxin treatment, lpr mice exhibited a reduced number of apoptotic positive cells, determined by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) method in different regions of the hippocampus, when compared to wild-type mice. In addition, treatment of lpr mice with KA did not produce significant changes in the transcriptional activity of genes related to apoptosis in the hippocampus, either in the fas and fas ligand genes or in caspase-4 and caspase-8 and the executioner caspase-3 genes, as occurred in wild type C57BL/6 mice. Thus, these data provide direct evidence that Fas signalling plays a key role in the induction of apoptosis in the hippocampus following KA treatment, making the inhibition of the death receptor pathway a potentially suitable target for excitotoxicity neuroprotection in neurological conditions such as epilepsy. PMID- 25119782 TI - Organizational, Cultural, and Psychological Determinants of Smart Infusion Pump Work Arounds: A Study of 3 U.S. Health Systems. AB - OBJECTIVES: We investigated nurse perceptions of smart infusion medication pumps to provide evidence-based insights on how to help reduce work around and improve compliance with patient safety policies. Specifically, we investigated the following 3 research questions: (1) What are nurses' current attitudes about smart infusion pumps? (2) What do nurses think are the causes of smart infusion pump work arounds? and (3) To whom do nurses turn for smart infusion pump training and troubleshooting? METHODS: We surveyed a large number of nurses (N = 818) in 3 U.S.-based health care systems to address the research questions above. We assessed nurses' opinions about smart infusion pumps, organizational perceptions, and the reasons for work arounds using a voluntary and anonymous Web based survey. Using qualitative research methods, we coded open-ended responses to questions about the reasons for work arounds to organize responses into useful categories. RESULTS: The nurses reported widespread satisfaction with smart infusion pumps. However, they reported numerous organizational, cultural, and psychological causes of smart pump work arounds. Of 1029 open-ended responses to the question "why do smart pump work arounds occur?" approximately 44% of the causes were technology related, 47% were organization related, and 9% were related to individual factors. Finally, an overwhelming majority of nurses reported seeking solutions to smart pump problems from coworkers and being trained primarily on the job. DISCUSSION AND CONCLUSIONS: Hospitals may significantly improve adherence to smart pump safety features by addressing the nontechnical causes of work arounds and by providing more leadership and formalized training for resolving smart pump-related problems. PMID- 25119783 TI - Sociocultural Factors Influencing Incident Reporting Among Physicians and Nurses: Understanding Frames Underlying Self- and Peer-Reporting Practices. AB - OBJECTIVES: Voluntary reporting of incidents is a common approach for improving patient safety. Reporting behaviors may vary because of different frames within and across professions, where frames are templates that individuals hold and that guide interpretation of events. Our objectives were to investigate frames of physicians and nurses who report into a voluntary incident reporting system as well as to understand enablers and inhibitors of self-reporting and peer reporting. METHODS: This is a qualitative case study-confidential in-depth interviews with physicians and nurses in General Internal Medicine in a Canadian tertiary care hospital. RESULTS: Frames that health care practitioners use in their reporting practices serve as enablers and inhibitors for self-reporting and peer reporting. Frames that inhibit reporting are shared by physicians and nurses, such as the fear of blame frame regarding self-reporting and the tattletale frame regarding peer reporting. These frames are underpinned by a focus on the individual, despite the organizational message of reporting for learning. A learning frame is an enabler to incident reporting. Viewing the objective of voluntary incident reporting as learning allows practitioners to depersonalize incident reporting. The focus becomes preventing recurrence and not the individual reporting or reported on. CONCLUSIONS: Physicians and nurses use various frames that bound their views of self and peer incident reporting-further progress should incorporate an understanding of these deep-seated views and beliefs. PMID- 25119784 TI - Patient Handoffs: Is Cross Cover or Night Shift Better? AB - OBJECTIVES: Studies show singular handoffs between health care providers to be risky. Few describe sequential handoffs or compare handoffs from different provider types. We investigated the transfer of information across 2 handoffs using a piloted survey instrument. We compared cross-cover (every fourth night call) with dedicated night-shift residents. METHODS: Surveys assessing provider knowledge of hospitalized patients were administered to pediatric residents. Primary teams were surveyed about their handoff upon completion of daytime coverage of a patient. Night-shift or cross-covering residents were surveyed about their handoff of the same patient upon completion of overnight coverage. Pediatric hospitalists rated the consistency of information between the surveys. Absolute difference was calculated between the 2 providers' rating of a patient's (a) complexity and (b) illness severity. Scores were compared across provider type. RESULTS: Fifty-nine complete handoff pairs were obtained. Fourteen and 45 handoff surveys were completed by a cross-covering and a night-shift provider, respectively. There was no significant difference in information consistency between primary and night-shift (median, 4.0; interquartile range [IQR], 3-4) versus primary and cross-covering providers (median, 4.0; IQR, 3-4). There was no significant difference in median patient complexity ratings (night shift, 3.0; IQR, 1-5, versus cross cover, 3.5; IQR, 1-5) or illness severity ratings (night shift, 2.0; IQR, 1-4, versus cross-cover, 3.0; IQR, 1-6) when comparing provider types giving a handoff. CONCLUSIONS: We did not find a difference in physicians' transfer of information during 2 handoffs among providers taking traditional call or on night shift. Development of tools to measure handoff consistency is needed. PMID- 25119785 TI - A Step Toward High Reliability: Implementation of a Daily Safety Brief in a Children's Hospital. AB - OBJECTIVES: Health care is a high-risk industry. To improve communication about daily events and begin the journey toward a high reliability organization, the Riley Hospital for Children at Indiana University Health implemented a daily safety brief. METHODS: Various departments in our children's hospital were asked to participate in a daily safety brief, reporting daily events and unexpected outcomes within their scope of responsibility. Participants were surveyed before and after implementation of the safety brief about communication and awareness of events in the hospital. The length of the brief and percentage of departments reporting unexpected outcomes were measured. RESULTS: The analysis of the presurvey and the postsurvey showed a statistically significant improvement in the questions related to the awareness of daily events as well as communication and relationships between departments. The monthly mean length of time for the brief was 15 minutes or less. Unexpected outcomes were reported by 50% of the departments for 8 months. CONCLUSIONS: A daily safety brief can be successfully implemented in a children's hospital. Communication between departments and awareness of daily events were improved. Implementation of a daily safety brief is a step toward becoming a high reliability organization. PMID- 25119786 TI - Application of Failure Mode Effect Analysis to Improve the Care of Septic Patients Admitted Through the Emergency Department. AB - BACKGROUND: Failure mode effect analysis (FMEA) is a proactive multistep tool used to analyze risks, identify failures before they occur, and prioritize preventive measures. METHODS: A multidisciplinary team trained on FMEA methodology analyzed the process of treatment of septic patients and recorded processes under 3 major phases (recognition of severe sepsis, referral, and resuscitation). The team identified potential failure modes in each process; assigned severity, occurrence, and detection scores for each; and calculated the risk priority numbers (RPNs). Finally, higher-priority failure modes (RPN of >=300) were analyzed to redesign the care process. RESULTS: We identified 27 processes and 48 failure modes with a mean RPN of 270. Twenty-two high-risk failures were identified by RPN of 300 or higher. All identified critical processes were related to phase 1 (recognition of sepsis) and phase 3 (resuscitation). The most critical process seemed to be related to the initial workup and treatment of septic patients, with 4 potential failure modes and a total RPN of 1485. CONCLUSIONS: Patient safety and care reliability issues are a major concern in health care. This study suggests that tools such as FMEA can enable a detailed analysis of the care process of septic patients by outlining potential failure modes and guiding improvement efforts. PMID- 25119787 TI - Improving Insulin Administration Through Redesigning Processes of Care: A Multidisciplinary Team Approach. AB - OBJECTIVES: This article describes a quality improvement project using a multidisciplinary team approach to improve the rate of errors of omission of preprandial subcutaneous coverage insulin orders. METHODS: A Diabetic Management Work Group was created to evaluate the system processes that affect success and failure of timely administration and documentation of preprandial coverage insulin, commonly referred to as sliding scale coverage. Data before and after the project were collected to evaluate the effectiveness of a process change through the bar code medication administration system, in which preprandial coverage insulin order sets were changed to eliminate errors of omission and improve documentation. RESULTS: A review of 833 random blood glucose measurements with corresponding short- or rapid-acting insulin coverage orders was conducted. A mean error of omission rate of 23.4% was identified with respect to coverage insulin that was clinically indicated by provider-ordered insulin set but not administered or documented in the electronic medication record. After process redesign and implementation, 951 blood glucose measurements with corresponding insulin coverage orders were randomly reviewed, and a mean of 10.7% of omission rate for coverage insulin administration was identified. This represented a decrease in omission of coverage insulin by 54% compared with preprocess improvement. CONCLUSIONS: Decreased errors of omission as well as improved administration and documentation of coverage insulin were demonstrated by this multimodal process change. Scheduled standardized order sets, extensive nursing staff education, and enhanced efficiency of the existing process led to improved outcomes. PMID- 25119788 TI - An overview of measurement activities in the partnership for patients. AB - The Partnership for Patients, launched in April 2011, is a national quality improvement initiative from the Department of Health and Human Services that has set ambitious goals for U.S. providers to improve patient safety and care transitions. This paper outlines the initiative's measurement strategy, describing four measurement-related objectives: (1) to track national progress toward the program goals that U.S. hospitals reduce preventable adverse events by 40% and readmissions by 20%; (2) to support local quality improvement measurement in participating hospitals by providing the appropriate tools, training, and programmatic structure; (3) to obtain feedback on hospital and contractor progress, in close to real time, so the project can be effectively managed; and (4) to evaluate the program's impact on adverse event and readmission rates. PMID- 25119789 TI - A multitasking functional group leads to structural diversity using designer C-H activation reaction cascades. AB - The C-H activation strategy has become one of the preferred methods to introduce chemical functionality to a chemically inert carbon atom. Intensive efforts have been devoted to developing either versatile bond formations (product structural diversity) or effective directing groups (substrate site selectivity). From the views of medicinal and synthetic practitioners, the C-H activation approach remains inadequate due to its limitation to point-to-point derivatization. Direct assembly of 3D molecular complexity in a single step remains elusive for this strategy. Towards this goal, a multitasking functional group is required to accomplish several missions in one pot: site selecitivity, cleavability and redox versatility. We demonstrate that an oxyacetamide group is such a multifunctional warhead that enables a series of C-H functionalization cascades and allows direct access to structurally diverse polycyclic heterocyles in one pot. The progress of these reaction cascades were fully controlled by oxidants and temperature. The proliferation of the reaction chain can be extended to a four-step cascade. PMID- 25119790 TI - Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I. AB - The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl beta-D glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production. PMID- 25119791 TI - Comparison of ready biodegradation estimation methods for fragrance materials. AB - Biodegradability is fundamental to the assessment of environmental exposure and risk from organic chemicals. Predictive models can be used to pursue both regulatory and chemical design (green chemistry) objectives, which are most effectively met when models are easy to use and available free of charge. The objective of this work was to evaluate no-cost estimation programs with respect to prediction of ready biodegradability. Fragrance materials, which are structurally diverse and have significant exposure potential, were used for this purpose. Using a database of 222 fragrance compounds with measured ready biodegradability, 10 models were compared on the basis of overall accuracy, sensitivity, specificity, and Matthews correlation coefficient (MCC), a measure of quality for binary classification. The 10 models were VEGA(c) Non-Interactive Client, START (Toxtree(c)), Biowin(c)1-6, and two models based on inductive machine learning. Applicability domain (AD) was also considered. Overall accuracy was ca. 70% and varied little over all models, but sensitivity, specificity and MCC showed wider variation. Based on MCC, the best models for fragrance compounds were Biowin6, VEGA and Biowin3. VEGA performance was slightly better for the <50% of the compounds it identified as having "high reliability" predictions (AD index >0.8). However, removing compounds with one and only one quaternary carbon yielded similar improvement in predictivity for VEGA, START, and Biowin3/6, with a smaller penalty in reduced coverage. Of the nine compounds for which the eight models (VEGA, START, Biowin1-6) all disagreed with the measured value, measured analog data were available for seven, and all supported the predicted value. VEGA, Biowin3 and Biowin6 are judged suitable for ready biodegradability screening of fragrance compounds. PMID- 25119792 TI - Strain superlattices and macroscale suspension of graphene induced by corrugated substrates. AB - We investigate the organized formation of strain, ripples, and suspended features in macroscopic graphene sheets transferred onto corrugated substrates made of an ordered array of silica pillars with variable geometries. Depending on the pitch and sharpness of the corrugated array, graphene can conformally coat the surface, partially collapse, or lie fully suspended between pillars in a fakir-like fashion over tens of micrometers. With increasing pillar density, ripples in collapsed films display a transition from random oriented pleats emerging from pillars to organized domains of parallel ripples linking pillars, eventually leading to suspended tent-like features. Spatially resolved Raman spectroscopy, atomic force microscopy, and electronic microscopy reveal uniaxial strain domains in the transferred graphene, which are induced and controlled by the geometry. We propose a simple theoretical model to explain the structural transition between fully suspended and collapsed graphene. For the arrays of high density pillars, graphene membranes stay suspended over macroscopic distances with minimal interaction with the pillars' apexes. It offers a platform to tailor stress in graphene layers and opens perspectives for electron transport and nanomechanical applications. PMID- 25119794 TI - Evolution of quality of life in patients with Korsakoff's syndrome in a long-term care facility. AB - BACKGROUND: Korsakoff's syndrome (KS) is a neuropsychiatric disorder characterized by severe amnesia. Quality of life (QoL) is becoming an increasingly used outcome measure in clinical practice but little is known about QoL in KS and how it may change over time. The purpose of this study was therefore to assess the QoL in patients with KS at baseline and with a 20-month follow-up. METHODS: The current study is a longitudinal study on the QoL in patients with KS living in two long-term care facilities for KS patients in the Netherlands. QoL was scored with the proxy-based QUALIDEM scale with a 20-month follow-up. RESULTS: Of the 72 KS patients included at baseline, 57 KS patients had a follow-up QoL score (79.2%). On the subscales "Feeling at home," "Positive affect," and "Care relationship" of the QUALIDEM, there was a better QoL in the follow-up, although effects were relatively small. Other subscales indicated a stable QoL over time. There were inter-relations between changes in subscales. CONCLUSIONS: The main finding of this study is that patients with KS on average do show a relatively stable moderate to good QoL despite the severity of the syndrome. On specific subscales, there is a small increase in QoL over time. Results do suggest that prolonged stay in a long-term care facility for KS patients does have a neutral to a positive effect on QoL in KS. PMID- 25119795 TI - PM2.5 constituents and hospital emergency-room visits in Shanghai, China. AB - Although ambient PM2.5 has been linked to adverse health effects, the chemical constituents that cause harm are largely unclear. Few prior studies in a developing country have reported the health impacts of PM2.5 constituents. In this study, we examined the short-term association between PM2.5 constituents and emergency room visits in Shanghai, China. We measured daily concentrations of PM2.5, organic carbon (OC), elemental carbon (EC), and eight water-soluble ions between January 1, 2011 and December 31, 2012. We analyzed the data using overdispersed generalized linear Poisson models. During our study period, the mean daily average concentration of PM2.5 in Shanghai was 55 MUg/m(3). Major contributors to PM2.5 mass included OC, EC, sulfate, nitrate, and ammonium. For a 1-day lag, an interquartile range increment in PM2.5 mass (36.47 MUg/m(3)) corresponded to 0.57% [95% confidence interval (CI): 0.13%, 1.01%] increase of emergency room visits. In all the three models used, we found significant positive associations of emergency room visits with OC and EC. Our findings suggest that PM2.5 constituents from the combustion of fossil fuel (e.g., OC and EC) may have an appreciable influence on the health impact attributable to PM2.5. PMID- 25119793 TI - Bromelain surface modification increases the diffusion of silica nanoparticles in the tumor extracellular matrix. AB - Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of therapeutics and drug delivery systems in cancer parenchyma. This biological barrier limits the efficacy of promising therapeutic approaches including the delivery of siRNA or agents intended for thermoablation. After extravasation due to the enhanced penetration and retention effect of tumor vasculature, typical nanotherapeutics are unable to reach the nonvascularized and anoxic regions deep within cancer parenchyma. Here, we developed a simple method to provide mesoporous silica nanoparticles (MSN) with a proteolytic surface. To this extent, we chose to conjugate MSN to Bromelain (Br-MSN), a crude enzymatic complex, purified from pineapple stems, that belongs to the peptidase papain family. This surface modification increased particle uptake in endothelial, macrophage, and cancer cell lines with minimal impact on cellular viability. Most importantly Br MSN showed an increased ability to digest and diffuse in tumor ECM in vitro and in vivo. PMID- 25119797 TI - [Triazole antifungal agents: practice guidelines of therapeutic drug monitoring and perspectives in treatment optimization]. AB - Antifungal triazole agents (fluconazole, voriconazole, itraconazole and posaconazole) are widely used for the management of invasive fungal infections (IFI). These drugs are indicated both for the prophylaxis and treatment of IFI, particularly in candidiasis and aspergillosis, major cause of mortality in immunocompromised patients. Due to a large interindividual pharmacokinetic variability leading to sub-therapeutic or toxic concentrations and to concentration-efficacy and/or -toxicity relationships, therapeutic drug monitoring (TDM) of antifungal triazole is fully justified. This review provides an overview of literature based data that confirm the usefulness of such TDM and its level of evidence as well as the practical guidelines for its implementation. In addition, we discuss the interest of new tools to improve the clinical management of IFI, such as genotyping tests optimizing initial voriconazole dosing regimen or the development of a new solid oral tablet of posaconazole improving its bioavailability and limiting absorption disorders. PMID- 25119798 TI - [Pharmacogenetics and prediction of side effects of drugs]. AB - Drug response is often variable from one individual to another, which sometimes makes them difficult to use when the therapeutic range is narrow. This interindividual variability in response can be explained in part by genetic factors affecting the metabolism, transport and the mechanism of action of drugs. Pharmacogenetics studies the genetic mechanisms involved in the response to drugs in order to optimize drug therapy, both in terms of efficacy and job security. This article summarizes the most known present clinical applications that illustrate the benefit of pharmacogenetic tests available to the clinician and are feasible for routine therapeutic management of patients (prediction of efficacy and toxicity of drugs), but also to demonstrate the benefit of pharmacogenetic tests in terms of health economics (reducing the incidence of hospitalizations for adverse drug events). PMID- 25119799 TI - [Determination of the plasma global antioxidant capacity: a critical review]. AB - With respect to prevention of cardiovascular diseases and cancers, the healthcare professionals are more and more interested in the blood determination of antioxidants (vitamins C and E, carotenoids, glutathione, ubiquinone, antioxidant enzymes). The major problem of these analysis is their elevated cost. At the request of the healthcare professionals, the laboratories of clinical biology suggest the measurement of the plasma global antioxidant capacity (GAC) as a replacement of the individual determination of all these antioxidants. The present review shows that such a test presents a large number of gaps, the major one being that it essentially reflects the plasma concentration of uric acid and proteins. On basis of nine arguments, we show that the measurement of the plasma GAC cannot be considered as an in vivo marker of oxidative stress nor lead to the prescription antioxidant complement. PMID- 25119800 TI - [Analytical performances of SPAPLUS(r) turbidimeter for the dosage of immunoglobulins and beta-2 microglobulin in serum]. AB - We evaluated the analytical performances of the SPAPLUS((r)) immunoturbidimeter assays manufactured by The Binding Site((r)) for the quantification of thirteen immunological parameters in serum: IgG, IgA, IgM and IgD immunoglobulins, IgG subclasses (1 to 4), IgA subclasses (1 and 2), beta-2 microglobulin, free light chains kappa and lambda. The within-day precision (repeatability) and the between day precision (reproducibility) were obtained for two or three concentration levels depending of the parameter and were below the recommendations of the manufacturer, except for the repeatability of IgG1 (at a level of concentration of 6.7 g/L). An agreement above 90% (with Bland and Altman analysis) was observed between the results obtained with SPAPLUS((r)) and those obtained with the nephelometer IMMAGE((r)) 800 or radial immunodiffusion. The evaluation confirmed the linearity of the assays and the absence of contamination for all the parameters tested. We also assessed the practicability of the SPAPLUS((r)) in terms of maintenance, frequency of calibration and cadence tests. The SPAPLUS((r)) immunoturbidimeter displays good analytical performances for the immunological parameters evaluated in the present work. PMID- 25119801 TI - [Evaluation of the quality of clinical practice guidelines published in the Annales de Biologie Clinique with the help of the EFLM checklist]. AB - Several tools are available to help evaluate the quality of clinical practice guidelines (CPG). The AGREE instrument (Appraisal of guidelines for research & evaluation) is the most consensual tool but it has been designed to assess CPG methodology only. The European federation of laboratory medicine (EFLM) recently designed a check-list dedicated to laboratory medicine which is supposed to be comprehensive and which therefore makes it possible to evaluate more thoroughly the quality of CPG in laboratory medicine. In the present work we test the comprehensiveness of this check-list on a sample of CPG written in French and published in Annales de biologie clinique (ABC). Thus we show that some work remains to be achieved before a truly comprehensive check-list is designed. We also show that there is some room for improvement for the CPG published in ABC, for example regarding the fact that some of these CPG do not provide any information about allowed durations of transport and of storage of biological samples before analysis, or about standards of minimal analytical performance, or about the sensitivities or the specificities of the recommended tests. PMID- 25119796 TI - [Weakening osteopathies, chronic kidney disease, malabsorption, biological anomalies of calium/phosphorus metabolism: appropriate indications for a reasoned reimbursment of serum vitamin D measurement]. PMID- 25119802 TI - [Comparative study of parathormone and vitamin D measurements by three automats: ADVIA Centaur XP(r) (Siemens), ISYS(r) (IDS) and Liaison(r) (Diasorin)]. AB - Vitamin D (Vit.D) and parathormone (PTH) measurements are usually prescribed for phosphocalcic metabolism assessment and, especially for Vit.D, more and more frequently for other pathologies. In order to step up to automated techniques for these analysis in our laboratory, we tested 3 devices: ADVIA Centaur XP((r)) (Siemens), ISYS((r)) (IDS) and Liaison((r)) (Diasorin), which allow to simultaneously quantify Vit.D and PTH. The aim of this study was to evaluate the fidelity of these methods as well as study the correlation between them and the radioimmunological techniques previously used in our laboratory : " ELSA PTH " (Iba Cisbio International) and " 25-OH D " (IDS). The comparison of PTH analysis was performed on a population of chronic renal failure patients undergoing haemodialysis. According to our study, the 3 devices show acceptable analytical performances; anyway the measurements realized on the ISYS analyzer are the ones showing the best results in terms of fidelity, and the closest results to those obtained with the RIA reference techniques. PMID- 25119803 TI - Relationships between pharmacokinetic parameters of carbamazepine and therapeutic response in patients with bipolar disease. AB - This study aimed to assess the relationship between plasma levels of carbamazepine and its active metabolite 10,11-epoxide-carbamazepine, and the therapeutic response in patients with bipolar disease. Thirteen patients were kept on a fixed individual dose of carbamazepine for 19 weeks under psychiatric care. Steady-state plasma concentrations of carbamazepine and its metabolite 10,11-epoxide-carbamazepine were measured at weeks 4, 12, and 20 by HPLC essay. Simultaneously, the psychopathologic state was assessed using the Brief Psychiatric rating scale (BPRS). Upon correlational analysis, mean BPRS scores did not correlate with the plasma levels of carbamazepine, whereas both mean plasma levels of 10, 11-epoxide-carbamazepine concentrations and 10,11-epoxide carbamazepine to plasma carbamazepine ratio were closely correlated with mean values of BPRS scores (r = 0.80, p =10(-4), r= -0.89, p =10(-3) respectively). Optimum therapeutic response was observed among patients who had a plasma metabolite level of 1.4 MUg/mL and a plasma carbamazepine concentrations of 7 MUg/mL simultaneously. These results suggest that both plasma carbamazepine and 10,11-epoxide-carbamazepine levels must be fixed to achieve optimum therapeutic response. In order to reach these conditions, inhibitor drugs (such as valproic acid) or inductor drugs (such as phenobarbital) of epoxyde-hydrolase might be coadministered with the carbamazepine in order to adapt the plasma level of 10,11 epoxide-carbamazepine. PMID- 25119804 TI - [EEQ in clinical embryology: a starting program]. AB - Every laboratory including those working in assisted reproductive technologies have to be accredited EN ISO 15189 before 2020. This standardisation includes an external quality evaluation (EQE). In order to work out an EQE tool, we used images extracted from our own database developed during daily practice. We achieved an easily online tool called: "EEQ en embryologie clinique", developed on Biologie prospective web site with ART French biologists Association (Blefco) expertise in evaluation of early human embryonic stages. In 2013, 38 ART laboratories participate to the first program with more than 90% of appropriates results. The present article aims at describing this tool and discussing its limits. PMID- 25119805 TI - [Pathophysiological characterization of metabolic syndrome in overweight, obese and type 2 diabetic Algerian subjects: interest of adipokines as dysmetabolic biomarkers]. AB - The body fat accretion (BFA) is correlated to energy homeostasis and/or hemodynamic dysfunction, being mediated by insulin resistance, dyslipidemia and recently by adipokines. OBJECTIVES: In this study, we investigated the associations between metabolic syndrome markers and the secretion disturbs of leptin, adiponectin and resistin during overweight (OW), obesity (OB) and type 2 diabetes de type 2 (T2DM) stages. PATIENTS AND METHODS: The study was undertaken on 240 subjects who were divided in 3 groups: overweight, obese and diabetic groups, according to age, sex and the BMI value. The metabolic syndrome was investigated according to the NCEP/ATPIII criteria. Insulin resistance was assessed by HOMA model. Metabolic parameters were determined on Cobas(r). Adipokines (leptin, adiponectin, resistin) by enzyme linked immunosorbent assay on human ELISA reader - Biotek ELX 800. RESULTS: The adipokines secretion is influenced by the adipose tissue accretion and insulin resistance state. The BFA in OB and OW subjects is positively correlated to the increase of serum leptin, whereas the serum adiponectin is reduced. The serum adipokines profile is modulated differently between men and women, particularly for leptin. Resistin secretion follows the evolution of leptinemia. CONCLUSION: It appears that adipokines as major dysmetabolic biomarkers, and can be considered as relevant biological tools in the diagnosis of cardiovascular and T2DM predictive risk in overweight and obese subjects. PMID- 25119806 TI - [Cytogenetics study of chromosomal instability in Fanconi anemia in Tunisia]. AB - Cells of Fanconi anemia (FA) is characterized by cellular and chromosomal hypersensitivity to DNA cross-linking agents. We tested mitomycin C at 25 ng/mL, 40 ng/mL and diepoxybutane 0.1 MUg/mL in order to select a reference technique in the diagnosis of AF. We also studied the mitotic segregation of sex chromosomes. Our study focused on 73 patients with aplastic anemia suspecting AF and also 17 healthy controls. Thus, the MMC 25 ng/mL with a sensitivity to detect AF cells. DEB, by contrast, showed better specificity. FISH study shows the presence of instability in the AF mitotic cells. The association for routine diagnosis of MMC 25 ng/mL and DEB 0.1 mcg/mL, and the search for a mitotic instability by FISH is the best way of cytogenetic diagnosis of AF. PMID- 25119807 TI - [Another case of the rare complications of chronic lymphocytic leukemia: angioedema]. AB - Angioedema is a rare but may be serious (laryngeal edema). This is a recurrent edema, subcutaneous and/or submucosal, whose cause is a hereditary or acquired deficiency in C1 inhibiteur (C1 inhibitor fraction of complement). We present the case of a 56 years old patient who showed recurrent episodes of swelling of the face and hands in association with chronic lymphocytic leukemia stage A. The exploration of the complement pathway has allowed retaining the diagnosis of acquired angioedema type I. The association of angioedema and lymphoproliferative syndrome is rare; we present this interesting case to discuss it from the literature data. PMID- 25119808 TI - A rare pediatric case of cutaneous gamma/delta T-cell lymphoma. AB - Cutaneous gamma/delta T-cell lymphoma (CGD-TCL) is a recent entity described in the newly revised World health organization-European organization for research and treatment of cancer classification of cutaneous lymphomas. Only a few cases have been reported, of which two pediatric cases. A 15 years old child with a 6 months history of polyadenopathy, cutaneous lesions, general edema and deterioration of general condition was hospitalized. Results from laboratory testing, cutaneous histopathology and immunohistochemistry showed a primary CGD TCL. Staging was completed by a total body computed tomography. Therapy was planified with SMILE protocol. It is a highly aggressive tumor resistant to chemotherapy, immunotherapy, and radiation therapy. The GDTCL is characterized by a worse prognosis with a median survival of 15 months. Early diagnosis is essential and aggressive therapy is necessary. PMID- 25119809 TI - [Gemella haemolysans brain abscess in a child with complex congenital heart disease]. AB - Gemella haemolysans, a Gram positive cocci which are deemed to be the normal inhabitant of the mucous membranes of the oropharynx, has been recognized as a pathogen involved in abscess formation. The aim of this case report is to demonstrate that it is also involved in brain abscess in children. We report, to our knowledge, the first pediatric case of Gemella haemolysans brain abscess in an 11 years old child carrying a complex congenital heart disease (dextrocardia with single right ventricle) which evolved favorably under antibiotic therapy. Because of its similarity with Streptococcus viridans groupe, Gemella haemolysans often remains under-diagnosed in the laboratory. The contribution of microbiologists in its correct identification is very important. PMID- 25119810 TI - [Immunoanalytical characteristics of galectin-3]. AB - This paper points out the structural and physiological data of galectin-3, and emphasizes its role in cardiac fibrosis and heart failure pathophysiology. Then we summarize the optimal conditions for sampling, assays and we discuss the interpretation of results. PMID- 25119811 TI - [Metabolic and inflammatory profiles in polycystic ovary syndrome associated to weight excess]. AB - Polycystic ovary syndrome (PCOS) and weight excess exhibited metabolic abnormalities and elevated cardiovascular risk. Our objective was to assess metabolic and inflammatory profiles in women with PCOS associated to weight excess; 85 women were enrolled. Four groups were then identified with and without PCOS and/or weight excess. Hyperlipidemia was significantly more observed in the two groups with weight excess. In whom insulinresistance and high sensitive C reactive protein were also elevated. Abnormalities observed when PCOS and weight excess are associated would mimic these observed in isolated weight excess with some particularities. PMID- 25119812 TI - Pharmacological and dietary agents for colorectal cancer chemoprevention: effects on polyamine metabolism (review). AB - Chemoprevention is the long-term use of different chemical agents, both synthetic and natural, to prevent or delay the onset of disease. Since colorectal cancer has a significant environmental component, it is an ideal disease in which to evaluate the potential benefits of chemopreventive agents. The polyamines, spermine, spermidine and putrescine have been involved in almost all the steps of colorectal tumorigenesis. Consequently, polyamine biosynthesis and catabolism can be considered as promising targets for cancer chemoprevention. A variety of drug formulations have been tested for their efficacy in affecting polyamines in a strategy of colorectal cancer prevention. Different molecules, such as biosynthesis inhibitors and catabolism inducers, have been proposed alone or in combination with other drugs proved to diminish the colorectal cancer risk. Interestingly, also diet can play a role in cancer prevention by affecting polyamines. Several dietary components, such as probiotics or flavonoids, have been shown to affect the polyamine metabolic pathway in colorectal neoplastic tissue. On the other hand, the polyamines ingested with diet might contrast the above cited effects shown by both drugs and nutritional factors. It is, therefore, fundamental to acquire more data also on these aspects in view of an innovative approach to colorectal oncology. This review summarizes data on the role of polyamine metabolism in neoplastic transformation of colorectal mucosa and as possible target for colorectal cancer chemoprevention. Attention will be focused on the influence of drugs and nutritional factors on polyamine metabolism, as well as the role played by dietary polyamines. PMID- 25119813 TI - Dinuclear zinc(II) complexes with hydrogen bond donors as structural and functional phosphatase models. AB - It is becoming increasingly apparent that the secondary coordination sphere can have a crucial role in determining the functional properties of biomimetic metal complexes. We have therefore designed and prepared a variety of ligands as metallo-hydrolase mimics, where hydrogen bonding in the second coordination sphere is able to influence the structure of the primary coordination sphere and the substrate binding. The assessment of a structure-function relationship is based on derivates of 2,6-bis{[bis(pyridin-2-ylmethyl)amino]methyl}-4 methylphenol (HBPMP = HL(1)) and 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-6-{[(2 hydroxybenzyl)(pyridin-2-ylmethyl)amino]methyl}-4-methylphenol (H2BPBPMP = H2L(5)), well-known phenolate-based ligands for metallo-hydrolase mimics. The model systems provide similar primary coordination spheres but site-specific modifications in the secondary coordination sphere. Pivaloylamide and amine moieties were chosen to mimic the secondary coordination sphere of the phosphatase models, and the four new ligands H3L(2), H3L(3), HL(4), and H4L(6) vary in the type and geometric position of the H-bond donors and acceptors, responsible for the positioning of the substrate and release of the product molecules. Five dinuclear Zn(II) complexes were prepared and structurally characterized in the solid, and four also in solution. The investigation of the phosphatase activity of four model complexes illustrates the impact of the H bonding network: the Michaelis-Menten constants (catalyst-substrate binding) for all complexes that support hydrogen bonding are smaller than for the reference complex, and this generally leads to higher catalytic efficiency and higher turnover numbers. PMID- 25119816 TI - Orientational and vibrational relaxation dynamics of perylene in the cyclohexane ethanol binary solvent system. AB - The rotational dynamics and vibrational population relaxation of the nonpolar probe molecule perylene have been studied in a series of ethanol-cyclohexane binary solvent mixtures, with the goal of relating solvent system composition to local organization. Steady-state spectroscopic data show that there is a discontinuous dependence of the spectroscopic origin on binary solvent system composition for perylene. Both rotational diffusion and vibrational population relaxation time constants show a clear discontinuity between 5% and 7.5% (v/v) ethanol in cyclohexane, suggesting a discontinuous change on molecular scale rearrangement in the chromophore local environment. We interpret these results in the context of the chromophore residing in an environment that is not homogeneous on the molecular scale and changes in its average conformation with binary solvent system composition. PMID- 25119814 TI - Increasing and decreasing the ultrastability of bacterial chemotaxis core signaling complexes by modifying protein-protein contacts. AB - The chemosensory signaling array of bacterial chemotaxis is composed of functional core units containing two receptor trimers of dimers, a homodimeric CheA kinase, and two CheW adaptor proteins. In vitro reconstitutions generate individual, functional core units and larger functional assemblies, including dimers, hexagons, and hexagonal arrays. Such reconstituted complexes have been shown to have both quasi-stable and ultrastable populations that decay with lifetimes of 1-2 days and ~3 weeks at 22 degrees C, respectively, where decay results primarily from proteolysis of the bound kinase [Erbse, A. H., and Falke, J. J. (2009) Biochemistry 48, 6975-6987; Slivka, P. F., and Falke, J. J. (2012) Biochemistry 51, 10218-10228]. In this work, we show that the ultrastable population can be destabilized to the quasi-stable level via the introduction of a bulky tryptophan residue at either one of two essential protein-protein interfaces within the core unit: the receptor-kinase contact or kinase-adaptor interface 1. Moreover, we demonstrate that the quasi-stable population can be made ultrastable via the introduction of a disulfide bond that covalently stabilizes the latter interface. The resulting disulfide at least doubles the functional lifetime of the ultrastable population, to >=5.9 weeks at 22 degrees C, by protecting the kinase from endogenous and exogenous proteases. Together, these results indicate that the ultrastability of reconstituted core complexes requires well-formed contacts among the receptor, kinase, and adaptor proteins, whereas quasi-stability arises from less perfect contacts that allow slow proteolysis of the bound kinase. Furthermore, the results reveal that ultrastability, and perhaps the size or order of chemosensory complexes and arrays, can be increased by an engineered disulfide bond that covalently cross links a key interface. Overall, it appears that native ultrastability has evolved to provide an optimal rather than maximal level of kinetic durability, suggesting that altered selective pressure could either increase or decrease the functional lifetime of core complexes. PMID- 25119815 TI - 14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) surrogates: carboxylate modifications. AB - The cytochrome P450 eicosanoid 14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET) is a powerful endogenous autacoid that has been ascribed an impressive array of physiologic functions including regulation of blood pressure. Because 14,15-EET is chemically and metabolically labile, structurally related surrogates containing epoxide bioisosteres were introduced and have become useful in vitro pharmacologic tools but are not suitable for in vivo applications. A new generation of EET mimics incorporating modifications to the carboxylate were prepared and evaluated for vasorelaxation and inhibition of soluble epoxide hydrolase (sEH). Tetrazole 19 (ED50 0.18 MUM) and oxadiazole-5-thione 25 (ED50 0.36 MUM) were 12- and 6-fold more potent, respectively, than 14,15-EET as vasorelaxants; on the other hand, their ability to block sEH differed substantially, i.e., 11 vs >500 nM. These data will expedite the development of potent and specific in vivo drug candidates. PMID- 25119817 TI - Airflow limitation following cardiopulmonary exercise testing and heavy-intensity intermittent exercise in children with cystic fibrosis. AB - The clinical importance of exercise testing and training in the healthcare management of young patients with cystic fibrosis (CF) is growing. The aim of the present study was to determine the incidence of airflow limitation following cardiopulmonary exercise testing (CPET) and heavy-intensity intermittent exercise (HIIE) in young patients with CF. Nineteen young patients with CF and respective paired-matched controls performed CPET and HIIE on separate days. Forced expiratory volume in one second (FEV1) was measured pre- and post each exercise modality. A fall in FEV1 of 10 % or greater was used to define airflow limitation. The incidence of airflow limitation was significantly greater in the CF group than in the controls following CPET (32 vs. 5 %; p = 0.03); however, no significant difference in the incidence of airflow limitation was shown following HIIE between the CF group and controls (11 vs. 16 %; p = 0.64). CONCLUSION: Our data show that the incidence of airflow limitation following CPET in young patients with CF is high. Therefore, clinicians may wish to identify whether young CF patients experience airflow limitation following strenuous exercise, such as CPET, before it is performed. However, HIIE carries a low risk for airflow limitation and may be prescribed as a safe, yet effective exercise modality for young patients with CF. PMID- 25119818 TI - The impact of preterm birth on participation in childhood occupation. AB - Outcome studies of premature babies have focused their assessments predominately on neurodevelopmental impairments without relating these deficits to the impact they have on a child's everyday life. This study aims to determine whether very 'preterm birth alone' impacts on a child's ability to participate in and carry out childhood activities. Forty-four former premature infants between 6 months and 5 years 6 months, born in Galway University Hospital, Ireland, without physical or intellectual disability, were compared with 51 age-matched term-born infants. Study infants had an average gestation of 29 weeks and birth weight of 1,145 g. Functional skills were assessed using the Adaptive Behavior Assessment Scale-II and the Assessment of Preschool Children's Participation. Premature infants had significantly lower mean scores in overall adaptive behaviour compared to term infants, regardless of whether chronological (difference = 13.6, 95% (CI) = [8.2, 19.1]) or corrected (difference = 6.6, 95% CI = [1.4, 11.8]) age was used. Premature infants had lower mean scores in conceptual, social and practical skills, but no difference was found between the groups in intensity or diversity of participation. CONCLUSION: Premature infants had significantly lower scores in adaptive behaviour than term infants. This measurable effect of preterm birth on 'childhood occupations' merits further investigation. PMID- 25119819 TI - First report of the symbiotic bacterium Xenorhabdus indica associated with the entomopathogenic nematode Steinernema yirgalemense. AB - The entomopathogenic nematode Steinernema yirgalemense is considered a promising agent in the biocontrol of insects. However, little is known about the bacteria living in symbiosis with the nematode. In this study, we have identified the only available bacterial strain (157-C) isolated from S. yirgalemense, as a member of the species Xenorhabdus indica. Identification was based on 16S rDNA, recA, dnaN, gltX, gyrB and infB gene sequence analyses. The relatedness of strain 157-C to the type strain of X. indica (DSM 17 382) was confirmed with DNA-DNA hybridization. The phenotypic characteristics of strain 157-C are similar to those described for the type strain of X. indica. This is the first report associating X. indica with S. yirgalemense. PMID- 25119820 TI - Is sperm hyaluronic acid binding ability predictive for clinical success of intracytoplasmic sperm injection: PICSI vs. ICSI? AB - Although intracytoplasmic sperm injection (ICSI) is now a widely-used technique, it is still of interest to improve our knowledge as to which is the best spermatozoon to be selected for ICSI. Infertile men have increased risks of producing aneuploid spermatozoa. Using hyaluronic acid (HA)-binding sperm selection may reduce the genetic risks such as chromosomal aberrations of offspring. In the present study we examined the clinical success of ICSI with HA selected sperm ('physiologic' ICSI, PICSI) compared to conventional ICSI, as well as the necessity to differentiate patients according to the initial HA-binding assay result (HBA score) and whether the sperm concentration or HBA score can provide additional information. We observed a significantly higher fertilization rate (FR) of the PICSI group with >60% HBA, implantation rate (IR) of the PICSI group with <= 60% HBA, and clinical pregnancy rate (CPR) in every PICSI group compared to the ICSI groups (p < 0.01). We also observed a significantly higher life birth rate (LBR) in the PICSI group with <= 60% HBA compared to ICSI patients with <= 60% HBA (p < 0.001). The pregnancy loss rate (PLR) was significantly lower in PICSI patients compared to the ICSI group (p < 0.0001). The FR, IR, CPR, and LBR of the PICSI group with <50% HBA were significantly higher and the PLR was lower than in the ICSI group with <50% HBA (p < 0.01). A statistically significant correlation was found between the sperm concentration and the HA-binding capacity (r = 0.62, p < 0.001). We found a closer relationship between HBA score and FR (r = 0.53, NS) than between sperm concentration and FR (r = 0.14, NS). HBA could be considered for sperm selection prior to ICSI because of its success and apparent ability to reduce genetic complications. However, this must be extended to a larger study. PMID- 25119823 TI - Geoscience themed issue: editorial. PMID- 25119821 TI - An easy and efficient method for native and immunoreactive Echinococcus granulosus antigen 5 enrichment from hydatid cyst fluid. AB - BACKGROUND: Currently, the serodiagnosis of cystic echinococcosis relies mostly on crude Echinococcus granulosus hydatid cyst fluid as the antigen. Consequently, available immunodiagnostic tests lack standardization of the target antigen and, in turn, this is reflected on poor sensitivity and specificity of the serological diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Here, a chromatographic method enabling the generation of highly enriched Antigen 5 (Ag5) is described. The procedure is very easy, efficient and reproducible, since different hydatid cyst fluid (HCF) sources produced very similar chromatograms, notwithstanding the clearly evident and extreme heterogeneity of the starting material. In addition, the performance of the antigen preparation in immunological assays was preliminarily assessed by western immunoblotting and ELISA on a limited panel of cystic echinococcosis patients and healthy controls. Following western immunoblotting and ELISA experiments, a high reactivity of patient sera was seen, with unambiguous and highly specific results. CONCLUSIONS/SIGNIFICANCE: The methods and results reported open interesting perspectives for the development of sensitive diagnostic tools to enable the timely and unambiguous detection of cystic echinococcosis antibodies in patient sera. PMID- 25119825 TI - Nut crop yield records show that budbreak-based chilling requirements may not reflect yield decline chill thresholds. AB - Warming winters due to climate change may critically affect temperate tree species. Insufficiently cold winters are thought to result in fewer viable flower buds and the subsequent development of fewer fruits or nuts, decreasing the yield of an orchard or fecundity of a species. The best existing approximation for a threshold of sufficient cold accumulation, the "chilling requirement" of a species or variety, has been quantified by manipulating or modeling the conditions that result in dormant bud breaking. However, the physiological processes that affect budbreak are not the same as those that determine yield. This study sought to test whether budbreak-based chilling thresholds can reasonably approximate the thresholds that affect yield, particularly regarding the potential impacts of climate change on temperate tree crop yields. County wide yield records for almond (Prunus dulcis), pistachio (Pistacia vera), and walnut (Juglans regia) in the Central Valley of California were compared with 50 years of weather records. Bayesian nonparametric function estimation was used to model yield potentials at varying amounts of chill accumulation. In almonds, average yields occurred when chill accumulation was close to the budbreak-based chilling requirement. However, in the other two crops, pistachios and walnuts, the best previous estimate of the budbreak-based chilling requirements was 19-32 % higher than the chilling accumulations associated with average or above average yields. This research indicates that physiological processes beyond requirements for budbreak should be considered when estimating chill accumulation thresholds of yield decline and potential impacts of climate change. PMID- 25119822 TI - The association of PTPN22 R620W polymorphism is stronger with late-onset AChR myasthenia gravis in Turkey. AB - A functional single nucleotide polymorphism (SNP) of the PTPN22 gene encoding a protein tyrosine phosphatase has been associated with autoimmune disorders including myasthenia gravis (MG). As the PTPN22 R620W polymorphism has a wide variation of allele frequencies among different populations, this polymorphism was investigated in MG in Turkey. An emphasis is put on MG subgroups according to autoantibody (Abs) production and presence of thymoma. DNA samples from 416 patients with clinically diagnosed generalized MG (231 with Abs to acetylcholine receptor, AChR-MG), 53 with Abs to muscle-specific kinase (MuSK-MG), 55 patients with no detectable Abs (SN-MG), 77 patients with thymoma (TAMG) and 293 healthy controls (HC) were genotyped for the SNP (PTPN22 R620W, C1858T, rs2476601). The PTPN22 T allele was increased in AChR-MG patients (odds ratio [OR]: 2.5, 95%CI: 1.2-5.1). The association was stronger in late disease-onset AChR (LOMG, OR: 3.1, 95%CI: 1.2-8.2). MuSK-MG, SN-MG and TAMG groups did not carry the variant allele more frequently than the HC. In contrast to findings in other autoimmune diseases, the distribution of the PTPN22 polymorphism in this population provides a susceptibility marker for AChR-MG. The strongest association is detected in patients with LOMG. PMID- 25119826 TI - Sport events and climate for visitors--the case of FIFA World Cup in Qatar 2022. AB - The effect of weather on sport events is not well studied. It requires special attention if the event is taking place at a time and place with extreme weather situations. For the world soccer championship in Qatar (Doha 2022), human biometeorological analysis has been performed in order to identify the time of the year that is most suitable in terms of thermal comfort for visitors attending the event. The analysis is based on thermal indices like Physiologically Equivalent Temperature (PET). The results show that this kind of event may be not appropriate for visitors, if it is placed during months with extreme conditions. For Doha, this is the period from May to September, when conditions during a large majority of hours of the day cause strong heat stress for the visitors. A more appropriate time would be the months November to February, when thermally comfortable conditions are much more frequent. The methods applied here can quantify the thermal conditions and show limitations and possibilities for specific events and locations. PMID- 25119828 TI - The CC chemokine ligand 2 (CCL2) polymorphism -2518A/G is associated with gout in the Chinese Han male population. AB - Gout is usually characterized by uric acid-induced recurrent attacks of acute inflammatory arthritis. CC chemokine ligand 2 (CCL2), a chemokine involved in the recruitment and migration of monocytes/macrophages, has previously been shown to be increased in the plasma of gout patients. In this study, we examined whether the CCL2 -2518A/G (rs1024611) single nucleotide polymorphism (SNP) affects susceptibility to gout in a Chinese Han male population. Genomic DNA from gout patients (n = 1,109) and ethnically matched gout-free controls (n = 1,034) was genotyped for the CCL2 -2518A/G SNP using polymerase chain reaction-restriction fragment length polymorphism. The Chi-square test was performed to investigate the association of genotypic and allelic frequencies between cases and controls, and the -2518G allele was shown to be associated with a significantly increased risk of gout development [P = 0.007, odds ratio 1.182, 95% confidence interval 1.047-1.335]. The GG genotypic distribution was also significantly different between cases and controls (adjusted P = 0.021). However, genotypic distributions and allelic frequencies did not indicate significant associations (P = 0.150 and P = 0.050, respectively) between tophi and non-tophi patients. Our findings support a key role for the CCL2 SNP -2518A/G in association with gout susceptibility in the Chinese Han male population. However, additional studies in other populations should be carried out to confirm this finding. PMID- 25119827 TI - An investigation into the relationship between anti-Helicobacter pylori and anti Saccharomyces cerevisiae antibodies in patients with axial spondyloarthritis and Crohn disease. AB - Spondyloarthritis (SpA) is a musculoskeletal inflammatory disease linked with immune responses to intestinal microbiota, and subclinical intestinal ulcerations that are closely related to inflammatory bowel diseases. Helicobacter pylori is a common cause of gastroduodenal ulceration, and anti-Saccharomyces cerevisiae antibodies (ASCA) are associated with intestinal inflammation in both Crohn disease (CD) and SpA. We investigated the relationship between H. pylori and ASCA. Ninety-one patients with axial SpA and forty with CD were included. ASCA IgG/IgA and anti-H. pylori IgG titers were assessed by ELISA. The proportion of ASCA+ patients in the positive and negative anti-H. pylori IgG groups with SpA and CD were compared using Chi-square tests, and correlations were evaluated using the Spearman's coefficient. Anti-H. pylori IgG titers were significantly negatively correlated with the ASCA IgG (r = -0.563, p < 0.001) and IgA (r = 0.342, p = 0.019) titers in the axial SpA patients. The same pattern of negative correlation was also observed in the CD patients. Anti-H. pylori+ serology was significantly more frequent in axial SpA patients than in those with CD (52.4 vs. 18.4 %, p < 0.001), while ASCA+ serology was significantly more frequent in CD patients than in SpA patients. A negative correlation between the anti-H. pylori titers and ASCA was found for axial SpA and CD. Anti-H. pylori+ serology was more frequent in SpA than in CD, while ASCA positivity was more frequent in CD patients than in those with SpA. A possible influence of H. pylori on the development of ASCA needs further investigation. PMID- 25119829 TI - Frequency of joint involvement in juvenile idiopathic arthritis during a 5-year follow-up of newly diagnosed patients: implications for MR imaging as outcome measure. AB - To assess the sequence and type of active joints in a cohort of newly diagnosed juvenile idiopathic arthritis (JIA) patients with full access to current treatment at first visit and during a follow-up period of 5-years, in order to identify an index joint/group of joints for magnetic resonance imaging in JIA. Patient charts of all consecutive newly diagnosed JIA patients with a follow-up duration of at least 5 years were analyzed. Patients were derived from two tertiary pediatric rheumatology centers. Patient characteristics and data concerning the presence of joints with arthritis and the use of medication were recorded. Findings from 95 JIA patients [39 (41 %) oligoarticular and 56 (59 %) polyarticular] were analyzed. At first visit, distribution of active joints among patients was as follows: knee (n = 70, 74 %), ankle (n = 55, 58 %), elbow (n = 23, 24 %), wrist (n = 23, 24 %), metacarpophalangeal (MCP) (n = 20, 21 %), proximal interphalangeal (PIP) (n = 13, 14 %), hip (n = 6, 6 %), shoulder (n = 5, 5 %), and distal interphalangeal (DIP) (n = 4, 4 %) joints. After a follow-up period of 5 years, the cumulative percentage of patients with specific joint involvement changed into: knee (n = 88, 93 %), ankle (n = 79, 83 %), elbow (n = 43, 45 %), wrist (n = 38, 40 %), MCP (n = 36, 38 %), PIP (n = 29, 31 %), shoulder (n = 20, 21 %), hip (n = 17, 19 %), and DIP (n = 9, 10 %) joints. Despite changes in treatment strategies over the years, the knee remains the most commonly involved joint at onset and during follow-up in JIA, followed by the ankle, elbow, and wrist. For the evaluation of outcome with MRI, the knee appears the most appropriate joint in JIA. PMID- 25119831 TI - Celiac symptoms in patients with fibromyalgia: a cross-sectional study. AB - Fibromyalgia is a chronic pain syndrome associated with numerous somatic symptoms including gastrointestinal manifestations of nonspecific nature. Celiac disease and nongluten sensitivity frequently evolve in adults with gastrointestinal and extraintestinal symptoms similar to those found among patients with fibromyalgia. The objective of the present study was to evaluate the presence of celiac-type symptoms among patients with fibromyalgia in comparison with healthy subjects and with those experienced by adult celiac patients and subjects with gluten sensitivity. A list of typical celiac-type symptoms was developed, comparing the frequency of presentation of these symptoms between patients with fibromyalgia (N = 178) and healthy subjects (N = 131), in addition to those of celiac patients and gluten-sensitive patients reported in the literature. The frequency of presentation of every celiac-type symptom, excepting anemia, was significantly higher among patients with fibromyalgia compared to controls (p < 0.0001). Regarding the existing data in the literature, the prevalence of fatigue, depression, cognitive symptoms and cutaneous lesions predominated among patients with fibromyalgia, whereas the prevalence of gastrointestinal symptoms was higher among patients with fibromyalgia compared to gluten-sensitive patients and was similar among patients with fibromyalgia and celiac disease patient. The symptomatological similarity of both pathologies, especially gastrointestinal symptoms, suggests that at least a subgroup of patients with fibromyalgia could experience subclinical celiac disease or nonceliac gluten intolerance. PMID- 25119830 TI - An insight into the gastrointestinal component of fibromyalgia: clinical manifestations and potential underlying mechanisms. AB - Fibromyalgia syndrome is characterized by chronic generalized pain accompanied by a broad symptomatologic spectrum. Besides chronic fatigue, sleep disturbances, headaches and cognitive dysfunction that are extensively described in the literature, a considerable proportion of patients with fibromyalgia experience gastrointestinal symptoms that are commonly overlooked in the studies that are not specifically dedicated to evaluate these manifestations. Nevertheless, various attempts were undertaken to explore the gastrointestinal dimension of fibromyalgia. Several studies have demonstrated an elevated comorbidity of irritable bowel syndrome (IBS) among patients with fibromyalgia. Other studies have investigated the frequency of presentation of gastrointestinal symptoms in fibromyalgia in a nonspecific approach describing several gastrointestinal complaints frequently reported by these patients such as abdominal pain, dyspepsia and bowel changes, among others. Several underlying mechanisms that require further investigation could serve as potential explanatory hypotheses for the appearance of such manifestations. These include sensitivity to dietary constituents such as gluten, lactose or FODMAPs or alterations in the brain-gut axis as a result of small intestinal bacterial overgrowth or subclinical enteric infections such as giardiasis. The gastrointestinal component of fibromyalgia constitutes a relevant element of the multidisciplinary pathophysiologic mechanisms underlying fibromyalgia that need to be unveiled, as this would contribute to the adequate designation of relevant treatment alternatives corresponding to these manifestations. PMID- 25119832 TI - Serum IL-33 level and IL-33 gene polymorphisms in Behcet's disease. AB - Behcet's disease (BD) is a chronic inflammatory disease. Increased productions of cytokines including interleukin (IL)-1beta and IL-18 are documented, and IL 1alpha and beta gene polymorphisms are associated with susceptibility to the disease. IL-33 is a recently discovered member of IL-1 cytokine family. The aim of the study was to detect serum IL-33 level and IL-33 gene polymorphisms in a cohort of BD. Unrelated 117 patients with BD and 149 healthy controls (HC) were enrolled. Serum IL-33 levels were analyzed by enzyme-linked immunosorbent assay method. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. Serum IL-33 level was not significantly different in the BD and HC groups (p > 0.05). However, its level was lower in the active BD patients compared to the inactive ones and HC group (p = 0.044 and p = 0.037, respectively). There was no significant difference in terms of the genotypic and allelic distributions of rs1157505 and rs1929992 polymorphisms (p > 0.05 for all). However, the TT variants of rs7044343 and rs11792633 polymorphisms were very rare, and the T allele frequencies of these polymorphisms were lower, in the BD group compared to the HC group (p < 0.0001 for all). The rs7044343 and rs11792633 variants of IL-33 gene are associated with the decreased risk of BD in our cohort. Therefore, it may be concluded that IL-33 acts a protective role on the pathogenesis of BD. PMID- 25119833 TI - Neuropsychiatric manifestations and associated autoantibodies in systemic lupus erythematosus patients from Western India. AB - Systemic lupus erythematosus with neuropsychiatric involvement (NPSLE) can be diagnosed clinically, but there is no definite serological biomarker established. The objectives of this study were to evaluate the neuropsychiatric involvement in systemic lupus erythematosus (SLE) patients and to detect the autoantibodies associated with them. Sixty NPSLE patients along with sixty SLE patients without neuropsychiatric involvement from Maharashtra, India, were included. All patients were clinically diagnosed using the American College of Rheumatology criteria. Disease activity was assessed using the systemic lupus erythematosus disease activity index. Antinuclear antibodies (ANA), anti-dsDNA, anti-neuronal antibodies were detected by indirect immunofluorescence test. Anti-ribosomal antibodies (anti-Rib-P) were tested by ELISA. NPSLE was diagnosed in age group ranging between 10 and 20 years compared with SLE patients without neuropsychiatric involvement (21-30 years). The most frequent symptoms were psychosis (75%), followed by seizures (58%), lupus headache (40%), cognitive dysfunction (36%), mood disorder (30%), cerebrovascular disease (20%), and anxiety (18%). ANA were present in all. The prevalence of anti-Rib-P was 26.6% in NPSLE and 16.6% in SLE patients without neuropsychiatric involvement. Anti neuronal antibodies were found in 56.7% in NPSLE and 43.4% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found to be highest in the patients of psychosis (66.6%) followed by central nerve system disease (63.63 %) and seizures (56.25%). There was an early onset of neuropsychiatric involvement. Anti-Rib-P antibodies as well as anti-neuronal antibodies did not show statistically significant correlation with neuropsychiatric manifestations in NPSLE patients. PMID- 25119835 TI - Histological and ultrastructural evidence for zinc sequestration in Solanum nigrum L. AB - The accumulation of contaminants in the environment due to anthropogenic activities is a matter of global concern. Solanum nigrum L. plants, able to accumulate zinc and hyperaccumulate cadmium, were challenged with 0.025 g Zn L( 1) during 35 days. The localization of Zn in roots, stems and leaves of S. nigrum plants was evaluated by autometallography (AMG) in order to determine the specific tissue, cell and subcellular compartments of Zn sequestration. This Zn concentration resulted in stunted plant growth but no other symptoms of Zn toxicity. Zinc concentration in the plants was highest in the roots, 666 mg Zn kg(-1) fresh weight (f.w.), and lower in the stems, 318 mg Zn kg(-1) f.w., and leaves, 101 mg Zn kg(-1) f.w. Roots of Zn-treated plants showed an underdeveloped structure but additional layers of proliferating cortical parenchyma cells. AMG of S. nigrum roots, stems and leaves revealed a generalized Zn distribution associated with the cell walls in all tissues. In the vasculature (xylem and phloem), Zn was observed at the plasma membrane-cell wall complex of vascular parenchyma cells and conducting elements. Conspicuous Zn deposits were detected in the vacuoles of cortical parenchyma and starch sheath, as well as in the tonoplast of the mesophyll cells. Our results suggest that Zn flux through the plant occurs via the xylem and phloem and associated parenchyma until it is conducted to permanent storage sites, namely, the apoplast and vacuoles of cortical parenchyma cells of the root, stem and the leaf mesophyll. PMID- 25119836 TI - A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial. AB - Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p < 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p < 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes. PMID- 25119834 TI - Emerging roles of pericytes in the regulation of the neurovascular unit in health and disease. AB - Pericytes of the central nervous system (CNS) are uniquely positioned within a multicellular structure termed the neurovascular unit (NVU) to provide crucial support to blood brain barrier (BBB) formation, maintenance, and stability. Numerous CNS diseases are associated with some aspect of BBB dysfunction. A dysfunction can manifest as one or multiple disruptions to any of the following barriers: physical, metabolic, immunological and transport barrier. A breach in the BBB can notably result in BBB hyper-permeability, endothelial activation and enhanced immune-endothelial interaction. How the BBB is regulated within this integrated unit remains largely unknown, especially as it relates to pericyte endothelial interaction. We summarize the latest findings on pericyte origin, possible marker expression, and availability within different organ systems. We highlight pericyte-endothelial cell interactions, concentrating on extra- and intra- cellular signaling mechanisms linked to platelet derived growth factor-B, transforming growth factor -beta, angiopoietins, Notch, and gap junctions. We discuss the role of pericytes in the NVU under inflammatory insult, focusing on how pericytes may indirectly affect leukocyte CNS infiltration, the direct role of pericyte-mediated basement membrane modifications, and immune responses. We review new findings of pericyte actions in CNS pathologies including Alzheimer's disease, stroke, multiple sclerosis, diabetic retinopathy, and HIV-1 infection. The uncovering of the regulatory role of pericytes on the BBB will provide key insight into how barrier integrity can be re-established during neuroinflammation. PMID- 25119837 TI - Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal dementia. AB - Daytime somnolence and sleep-wake cycle disturbances are commonly encountered symptoms in Frontotemporal Dementia (FTD). Orexin-A (Hypocretin-1) is a hypothalamic neuropeptide regulating the sleep-wake rhythm. We investigated the cerebrospinal-fluid (CSF) orexin levels in a population of FTD patients and evaluated whether there is a relationship between daytime somnolence and CSF orexin concentrations. CSF orexin levels were measured in a sample of FTD patients (n = 11) compared to a population of non-demented controls (n = 13) similar for age and sex. Moreover, CSF orexin concentrations were correlated with daytime somnolence investigated by means of the Epworth Sleepiness Scale (ESS) in both FTD patients and controls. FTD patients showed CSF orexin concentrations (164.3 +/- 66.45 vs 170.81 +/- 42.73 pg/mL) and ESS scores (7.45 +/- 4.36 vs 3.84 +/- 1.82) not different from controls. However, three FTD patients showed pathological daytime sleepiness (ESS > 10) coupled with the lowest CSF orexin levels. In addition, we found a significant negative correlation between CSF orexin levels and ESS scores in the FTD population (R = -0.91; p < 0.0001), which was not evident in the control group (R = 0.16; p > 0.05). This is the first study investigating CSF orexin concentrations in FTD. We did not find differences in CSF orexin concentrations between FTD patients and controls. However, a significant negative correlation between daytime somnolence and CSF orexin levels was evident in FTD patients. Moreover, we have found that pathological daytime somnolence was evident in those FTD patients with the lowest CSF orexin levels. Based on these findings, we argued that lower orexin levels may be permissive for increased daytime somnolence in FTD. PMID- 25119838 TI - Dopamine transporter availability in motor subtypes of de novo drug-naive Parkinson's disease. AB - Tremor dominant (TD) and akinetic-rigid type (ART) are two motor subtypes of Parkinson's disease associated with different disease progression and neurochemical/neuropathological features. The role of presynaptic nigrostriatal dopaminergic damage is still controversial, poorly explored, and only assessed in medicated patients. In this study, we investigated with FP-CIT SPECT the striatal dopamine transporter (DAT) availability in drug-naive PD patients with ART and TD phenotypes. Fifty-one de novo, drug-naive patients with PD underwent FP-CIT SPECT studies. Patients were evaluated with Unified Parkinson's Disease Rating Scale (UPDRS) part III and Hoehn and Yahr scale (H&Y) and divided into ART (24/51) and TD (27/51) according to UPDRS part III. ART and TD patients were not different with regard to age, gender, and disease duration. However, compared to TD, ART patients presented higher UPDRS part III (p = 0.01) and H&Y (p = 0.02) and lower DAT availability in affected and unaffected putamen (p = 0.008 and p = 0.007, respectively), whereas no differences were found in caudate. Moreover, in the whole group of patients, rigidity and bradykinesia, but not tremor scores of UPDRS part III were significantly related to FP-CIT binding in the putamen. These results suggest that in newly diagnosed drug-naive PD patients DAT availability might be different between ART and TD in relation to different disease severity. PMID- 25119839 TI - Detailing intra-lesional venous lumen shrinking in multiple sclerosis investigated by sFLAIR MRI at 7-T. AB - Intra-lesional venous lumen shrinking detectable by MRI was suggested as an in vivo marker of inflammation in multiple sclerosis (MS). In our study mean diameters of pre-, post- and intra-lesional venous sections were determined in 49 patients with MS or clinically isolated syndrome (CIS) using a pixel-wise analysis on susceptibility-weighted fluid-attenuated inversion recovery (sFLAIR) images and T2*-weighted (T2*w) imaging at 7 Tesla (T). We observed post-to-intra lesional venous lumen shrinking on T2*w images (p = 0.036) in an analysis of 338 venous sections. Pre-to-intra-lesional venous lumen reduction was only detectable in less than 50% of lesions and failed statistical significance when analysing T2*w (p = 0.325) and sFLAIR images (p = 0.258). In conclusion, thinning of intra lesional veins in MS is--if detectable at all--probably less severe than previously reported, and affects only a minority of MS lesions. PMID- 25119841 TI - Intracranial hemorrhage risk with the new oral anticoagulants: a systematic review and meta-analysis. AB - The new oral anticoagulants/non-vitamin K antagonists oral anticoagulants (NOACs) have recently reached the market and less is known about their safety in comparison to their efficacy. Therefore, we aimed to evaluate intracranial hemorrhage (ICH) risk with NOACs, the most feared adverse event of anticoagulation treatment. This is a systematic review and meta-analysis of phase III randomized controlled trials (RCTs) comparing NOACs versus any control and reporting ICH events. Studies were searched through Medline and Cochrane Library (April 2014). Reviews and reference lists were also screened. Random effects' meta-analysis was performed to derive pooled estimates expressed as relative risk (RR) and 95 % CI. Number needed to treat/harm (NNT/NNH) taking into account the baseline risk was also calculated. Heterogeneity was evaluated with I (2) test. 18 RCTs evaluating 148,149 patients were included. NOAC significantly reduced ICH risk compared to vitamin K antagonists (VKA) (RR 0.44; 95 % CI 0.36-0.54; I (2) = 37 %; NNT: 137 during 2 years) and to sequential treatment with low molecular weight heparin and VKA (RR 0.28; 95 % CI 0.12-0.65; I (2) = 0 %; NNT: 463 patients during 7 months). Compared to placebo, NOACs were associated with an increased ICH risk (RR 3.31; 95 % CI 1.59-6.90; I (2) = 0 %; NNH: 433 during 1 year). Results were similar for the different NOAC drugs and across the different clinical conditions. In patients requiring anticoagulation treatment, the risk of ICH is about half with the NOACs in comparison to standard antithrombotic treatment. This safer profile found in RCTs should be confirmed in real-world database studies. PMID- 25119842 TI - Hippocampal damage and affective disorders after treatment of cerebral aneurysms. AB - Despite good neurological outcome after the treatment of ruptured or incidental cerebral aneurysms, many patients complain about mood disturbances such as anxiety and depression. The present study investigated the nature of these affective disorders, their trigger factors, and corresponding structural brain changes. We assessed 63 patients matched by history of previous subarachnoid hemorrhage (SAH) and treatment modality (clipping vs. coiling) by a test battery including the Hospital Anxiety and Depression Scale (HADS) and beck depression inventory-II (BDI-II). MR imaging for the evaluation of structural changes included H(1)-MR spectroscopy, hippocampal volumetry, and diffusion tensor imaging (DTI). The applied multimodal imaging revealed no significant differences between patients with previous SAH and patients with incidental aneurysms; there were also no substantial differences between patients with and without previous SAH with respect to depression and anxiety. However, we observed significantly higher mean HADS scores in patients treated surgically versus patients treated by coiling (p < 0.01). BDI-II tended to be higher in surgically treated patients, but this difference appeared statistically insignificant. Surgically treated patients displayed substantial hippocampal damage in all imaging techniques: reduction in mean concentrations of N-acetylaspartate (p = 0.04), hippocampal volume reduction (p = 0.012), and diffusion disorder (p = 0.02). The structural alterations correlated significantly with the increased HADS scores. In contrast to endovascular treatment, aneurysm surgery seems to be associated with an increased incidence of mood disorders corresponding to hippocampal neuronal loss, independent of preceding SAH. PMID- 25119844 TI - Reducing central nervous system complications associated with the human immunodeficiency virus. PMID- 25119843 TI - The presence of dysautonomia in different subgroups of myasthenia gravis patients. AB - To analyze the presence of autonomic dysfunction in different subgroups of myasthenia gravis (MG) patients. Standard cardiovascular reflex tests according to Ewing, spectral and time domain analysis of heart rate variability (HRV) at rest were assessed in 27 patients with thymoma-associated acetylcholine receptor (AChR)-positive MG, 25 AChR-positive MG patients without thymoma and 23 patients with muscle-specific tyrosine kinase (MuSK) MG. All patients were compared to the healthy controls, matched for sex and age. In the group of AChR-positive MG patients with thymoma, hand grip (p < 0.05), orthostasis (p < 0.05), breathing test (p < 0.05) and Valsalva maneuver (p < 0.01) were more often pathological than in the controls. Analysis of the spectral domain of HRV showed increased low frequency (p < 0.05) and decreased high-frequency component (p < 0.05). Time domain parameters of HRV and baroreflex sensitivity (BRS) at rest were significantly reduced (p < 0.01). In the patients with AChR MG without thymoma, Valsalva maneuver test was more often pathological (p < 0.05) and higher rate of supraventricular extrasystoles (p < 0.01) was registered than in the healthy controls. In the patients with MuSK-positive MG, hand grip and Valsalva maneuver tests were more often pathological than in the controls (p < 0.05). Low-frequency component of the spectral domain of HRV (p < 0.05) and the frequency of cardiac arrhythmia were increased. BRS at rest was significantly lower in patients compared to the controls (p < 0.01). We determined the presence of autonomic failure in all subgroups of MG patients. Since autonomic dysfunction can lead to cardiac arrhythmias and even sudden death, it is of major importance to be aware of this association and to properly diagnose and treat these patients. PMID- 25119845 TI - Patients' perspectives on the impact of a new COPD diagnosis in the face of multimorbidity: a qualitative study. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide, often occurs in the presence of comorbidities, which may influence experience and management of the disease. No prior research seems to have gained perspectives of newly diagnosed primary care COPD patients in the context of multimorbidity. AIMS: This qualitative study aimed to explore the impact of a new diagnosis of COPD in the context of multimorbidity and also sought to gain a better understanding of how patients react to the diagnosis and incorporate it into their lives. METHODS: Participants were identified from a cohort of primary care patients with multimorbidity recently diagnosed with COPD. Data was collected via semi-structured interviews from nine male and eight female participants. Thematic analysis was performed and the data interpreted from a constructivist perspective. RESULTS: Five core themes regarding COPD were induced: (i) reaction to diagnosis, (ii) impact on function and health behaviour, (iii) factors influencing self-management capacity, (iv) healthcare utilisation and (v) interplay of comorbidities. Most participants had difficulty recognising the importance of COPD and its long-term implications. For many, the salience of another chronic condition outweighed COPD. Self-management capacity and utilisation of healthcare services were challenged by low prioritisation of COPD among other comorbidities. CONCLUSIONS: This study provides an insight into how primary care patients feel about being diagnosed with COPD, as well as their prioritisation of the disease in the context of multimorbidity. It highlights the need for tailored education and personalised management incorporating patients' perspectives in primary care. PMID- 25119846 TI - Simultaneous detection of distinct ubiquitin chain topologies by 19F NMR. AB - The dynamic interplay between ubiquitin (Ub) chain construction and destruction is critical for the regulation of many cellular pathways. To understand these processes, it would be ideal to simultaneously detect different Ub chains as they are created and destroyed in the cell. This objective cannot be achieved with existing detection strategies. Here, we report on the use of 19F Nuclear Magnetic Resonance (NMR) spectroscopy to detect and characterize conformationally distinct Ub oligomers. By exploiting the environmental sensitivity of the 19F nucleus and the conformational diversity found among Ub chains of different linkage types, we can simultaneously resolve the 19F NMR signals for mono-Ub and three distinct di Ub oligomers (K6, K48, and K63) in heterogeneous mixtures. The utility of this approach is demonstrated by the ability to interrogate the selectivity of deubiquitinases with multiple Ub substrates in real time. We also demonstrate that 19F NMR can be used to discern Ub linkages that are formed by select E3 ligases found in pathogenic bacteria. Collectively, our results assert the potential of 19F NMR for monitoring Ub signaling in cells to reveal fundamental insights about the associated cellular pathways. PMID- 25119848 TI - Characteristics of international staff victims of psychiatric patient assaults: review of published findings, 2000-2012. AB - Psychiatric patient assaults on staff are a worldwide occupational hazard that results in human suffering and dollar cost expense. International research in the 1990s documented the frequent occurrence of these assaults. This present paper reviewed the published, international literature on staff victim assaults during the first decade of the new century. The findings indicate assaults on staff remain a serious worldwide issue as it was in the 1990s, even with new policy initiatives in place meant to reduce such violence. The findings by continents and a detailed methodological inquiry are presented. PMID- 25119849 TI - Comment on: "Insulin glargine in a Brazilian state: should the government disinvest?". PMID- 25119847 TI - Suicidality in non-treatment seeking young adults with subsyndromal gambling disorder. AB - Gambling Disorder is associated with elevated rates of suicidal thoughts and acts. However, virtually nothing is known about suicidality in people with subsyndromal forms of gambling disorder. A total of 174 non-treatment seeking subjects were recruited for a study of impulsivity and met criteria for a subsyndromal form of DSM-5 gambling disorder (31.0 % females; mean age = 21.7 +/- 3.61 years). Subjects were categorized as being 'at risk of suicide' or 'no suicide risk' based on the Mini-International Neuropsychiatric Interview (MINI). Those with and without suicidality were compared on clinical and cognitive measures. 32 (18.4 %) met MINI criteria for suicidality. Suicidality was significantly associated with mood and anxiety disorders, greater rates of nicotine consumption, and relative impairments in decision-making and cognitive flexibility. These findings suggest that decision-making impairments may be implicated in the development of both gambling problems and suicidality. Future work should address causality, neural correlates, and tailored suicide prevention strategies for people with, or at risk for, disordered forms of gambling. PMID- 25119850 TI - Authors' reply to Dr. Malerbi: "Insulin glargine in a Brazilian state: should the government disinvest?". PMID- 25119851 TI - The buckling of single-layer MoS2 under uniaxial compression. AB - Molecular dynamics simulations are performed to investigate the buckling of single-layer MoS2 under uniaxial compression. The strain rate is found to have an important effect on the critical buckling strain, where higher strain rate leads to larger critical strain. The critical strain is almost temperature-independent for [Formula: see text] K, and it increases with increasing temperature for [Formula: see text] K owing to the thermal vibration assisted healing mechanism on the buckling deformation. The length-dependence of the critical strain from our simulations is in good agreement with the prediction of the Euler buckling theory. PMID- 25119852 TI - Responses to ROS inducer agents in zebrafish cell line: differences between copper and UV-B radiation. AB - Fish are commonly exposed to environmental pollutants, which in turns could induce an oxidative stress. So, it is important to understand the effects and the responses elicited by these toxicants in fish species, being fish cell lines important tools for this purpose. Thus, the aim of the present study was to compare the effects of copper and UV-B radiation exposure on zebrafish hepatocytes (ZFL lineage) in terms of reactive oxygen species (ROS) levels, sulfhydril groups content and mRNA levels of important genes related to cellular response to toxic agents. Exposure of ZFL cells to UV-B radiation (23.3 mJ/cm(2)) significantly increased levels of intracellular ROS and mRNA of both superoxide dismutase isoforms (sod1 and sod2), three glutathione S-transferase isoforms (gstalpha, gstu and gstpi) and a heat shock protein (hsp70). However, no changes in nonprotein sulfhydryl groups (NP-SH) content, as well as in the mRNA levels of genes related to glutathione (GSH) synthesis and recycling, were observed. Contrary to this, copper exposure (20 mg/L) diminished NP-SH content and increased the levels of mRNA of genes related to GSH synthesis (gclc and gs). Moreover, copper exposure increases the mRNA levels of some genes related to antioxidant defenses (gpx and gstpi), biotransformation reactions (cyp1a1) and protein repair (hsp70). In conclusion, these results demonstrated that both toxicants could increase ROS levels in ZFL cell line, but the responses are different, which could be related to activation of different signaling pathways. PMID- 25119853 TI - Effects of dietary cholesterol supplementation on growth and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed diets with cottonseed meal or rapeseed meal. AB - This study was conducted to evaluate the effects of cholesterol on growth and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed diets with cottonseed meal (CSM) or rapeseed meal (RSM). Four experimental diets were formulated to contain 550 g kg(-1) CSM or 450 g kg(-1) RSM with or without 9 g kg(-1) supplemental cholesterol. Growth rate and feed utilization efficiency of fish fed diets with 450 g kg(-1) RSM were inferior to fish fed diets with 550 g kg(-1) CSM regardless of cholesterol level. Dietary cholesterol supplementation increased the growth rate of fish fed diets with RSM, and growth rate and feed utilization efficiency of fish fed diets with CSM. Similarly, dietary cholesterol supplementation increased the plasma total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triiodothyronine levels, but decreased the plasma triglycerides and cortisol levels of fish fed diets with RSM or CSM. In addition, supplemental cholesterol increased the free cholesterol and TC levels in intestinal contents, but decreased the hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase activity of fish fed diets with RSM or CSM. These results indicate that 9 g kg(-1) cholesterol supplementation seems to improve the growth of rainbow trout fed diets with CSM or RSM, and the growth-promoting action may be related to the alleviation of the negative effects caused by antinutritional factors and/or make up for the deficiency of endogenous cholesterol in rainbow trout. PMID- 25119854 TI - Conditional expression of the type 2 angiotensin II receptor in mesenchymal stem cells inhibits neointimal formation after arterial injury. AB - Percutaneous coronary interventions (PCIs) are an effective treatment for obstructive coronary artery diseases. However, the procedure's success is limited by remodeling and formation of neointima. In the present study, we engineered rat mesenchymal stem cells (MSCs) to express type 2 angiotensin II receptor (AT2R) using a tetracycline-regulated system that can strictly regulate AT2R expression. We tested the ability of the modified MSCs to reduce neointima formation following arterial injury. We subjected rats to balloon injury, and reverse transcriptase polymerase chain reaction (RT-PCR) indicated no significant AT2R expression in normal rat arteries. Low expression of AT2R was observed at 28 days after balloon-induced injury. Interestingly, MSCs alone were unable to reduce neointimal hyperplasia after balloon-induced injury; after transplantation of modified MSCs, doxycycline treatment significantly upregulated neointimal AT2R expression and inhibited osteopontin mRNA expression, as well as neointimal formation. Taken together, these results suggest that transplantation of MSCs conditionally expressing AT2R could effectively suppress neointimal hyperplasia following balloon-induced injury. Therefore, MSCs with a doxycycline-controlled gene induction system may be useful for the management of arterial injury after PCI. PMID- 25119856 TI - Biological and analytical stability of a peripheral blood gene expression score for obstructive coronary artery disease in the PREDICT and COMPASS studies. AB - A gene expression score (GES) for obstructive coronary artery disease (CAD) has been validated in two multicenter studies. Receiver-operating characteristics (ROC) analysis of the GES on an expanded Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) cohort (NCT no. 00500617) with CAD defined by quantitative coronary angiography (QCA) or clinical reads yielded similar performance (area under the curve (AUC)=0.70, N=1,502) to the original validation cohort (AUC=0.70, N=526). Analysis of 138 non-Caucasian and 1,364 Caucasian patients showed very similar performance (AUCs=0.72 vs. 0.70). To assess analytic stability, stored samples of the original validation cohort (N=526) was re-tested after 5 years, and the mean score changed from 20.3 to 19.8 after 5 years (N=501, 95 %). To assess patient scores over time, GES was determined on samples from 173 Coronary Obstruction Detection by Molecular Personalized Gene Expression (COMPASS) study (NCT no. 01117506) patients at approximately 1 year post-enrollment. Mean scores increased slightly from 15.9 to 17.3, corresponding to a 2.5 % increase in obstructive CAD likelihood. Changes in cardiovascular medications did not show a significant change in GES. PMID- 25119855 TI - Imaging subclinical atherosclerosis: is it ready for prime time? A review. AB - Imaging subclinical atherosclerosis holds the promise of individualized cardiovascular (CV) risk assessment. The large arsenal of noninvasive imaging techniques available today is playing an increasingly important role in the diagnosis and monitoring of subclinical atherosclerosis. However, there is a debate about the advisability of clinical screens for subclinical atherosclerosis and which modality is the most appropriate for monitoring risk and atherosclerosis progression. This article offers an overview of the traditional and emerging noninvasive imaging modalities used to detect early atherosclerosis, surveys population studies addressing the value of subclinical atherosclerosis detection, and also examines guideline recommendations for their clinical implementation. The clinical relevance of this manuscript lies in the potential of current imaging technology to improve CV risk prediction based on traditional risk factors and the present recommendations for subclinical atherosclerosis assessment. Noninvasive imaging will also help to identify individuals at high CV who would benefit from intensive prevention or therapeutic interventions. PMID- 25119857 TI - A review of the role of electronic health record in genomic research. AB - Electronic health record (EHR)-driven genomic research is a recent strategy used to answer research questions using EHR data linked to DNA samples. In models using EHR, after the subject's DNA is collected, a linkage between the DNA sample and the EHR data is maintained. This makes the EHR the paramount source of phenotypic information. The National Human Genome Research Institute sponsored Electronic Medical Records and Genomics (eMERGE) network began in five sites in 2007 and was expanded to nine sites in 2012. This network has developed the methods and best practices for utilizing EHR as a tool for genomic research. Therefore, it is vital to understand the configuration of EHR used to capture data in clinical practice and feasibility of integration with clinical genetic test results. We present a detailed review of the role and importance of EHR in the field of genomic research. PMID- 25119858 TI - Risk of selected gastrointestinal toxicities in breast cancer patients treated with regimens containing lapatinib; a pooled analysis of randomized controlled studies. AB - We performed a pooled analysis of randomized controlled studies evaluating selected gastrointestinal adverse events associated with lapatinib use in breast cancer patients. Eligible studies included randomized Phase II and III trials of patients with breast cancer on lapatinib; describing events of diarrhea, nausea, vomiting and stomatitis. Our search strategy yielded 390 potentially relevant citations on lapatinib from Pubmed/Medline and other databases. After exclusion of ineligible studies, a total of 19 clinical trials were considered eligible for the analysis. The relative risk (RR) of all-grade diarrhea, nausea, vomiting and stomatitis were 3.09 (95% CI: 2.14-4.43; p < 0.00001), 1.24 (95% CI: 1.07- 1.43; p < 0.005), 1.35 (95% CI: 1.22-1.49; p = 0.0001), 1.96 (95% CI: 1.07-2.67; p = 0.02); respectively. Exploratory subgroup analysis showed no effect of disease stage on the RR of the relevant adverse events. While, The RR of high-grade diarrhea, nausea, vomiting and stomatitis were 6.63 (95% CI: 2.94-14.96; p < 0.00001), 1.37 (95% CI: 0.91-2.06; p = 0.13), 1.80 (95% CI: 1.21-2.68; p = 0.004), 2.44 (95% CI: 1.41-4.22 p < 0.001); respectively. Our pooled analysis has demonstrated that regimens containing lapatinib are associated with a significantly increased risk of high-grade diarrhea, vomiting and stomatitis in patients with breast cancer. Clinicians should be aware of these risks and perform regular clinical monitoring. PMID- 25119859 TI - Antioxidant defense and hepatoprotection by procyanidins from almond (Prunus amygdalus) skins. AB - Procyanidins, polymeric flavan-3-ols, are known to possess antioxidant, antiatherogenic, and anticarcinogenic properties. In the present study, we investigated the role of almond (Prunus amygdalus) skin procyanidins (ASP) in regulating the protein expression of phase II detoxifying and antioxidant enzymes in HepG2 cells and acetaminophen (APAP)-treated hepatotoxic mice. Treatments of ASP significantly induced the expression of phase II enzymes including NAD(P)H: quinoneoxidoreductase 1, catalase, glutathione peroxidase, and superoxide dismutase in the cells and mice. ASP also potently enhanced the expression of nuclear factor-E2-related factor 2 (Nrf2) and antioxidant response element (ARE) reporter gene activity in vitro. APAP-induced hepatotoxic markers including AST and ALT in mice were inhibited by ASP administration. However, regulation of upstream kinases by ASP was different between in vitro and in vivo models. Collectively, ASP could induce the activation of Nrf2/ARE-mediated phase II detoxifying/antioxidant enzymes but with differential regulation on upstream kinases between in vitro and in vivo. PMID- 25119860 TI - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hormones of energy balance in a TCDD-sensitive and a TCDD-resistant rat strain. AB - One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 MUg/kg) of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR) expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive Long-Evans rats, while there were few alterations in the resistant Han/Wistar strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated several of the perturbations to be secondary to energy deficiency. Notable increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone, which links these hormones to the wasting syndrome. The newly found energy balance regulators, insulin-like growth factor 1 and fibroblast growth factor 21 (FGF-21), appeared to function in concert in body weight loss-induced metabolic state, and FGF-21 was putatively linked to increased lipolysis induced by TCDD. Finally, we demonstrate a reverse set of changes in the AHR protein and mRNA response to TCDD and feed restriction, suggesting that AHR might function also as a physiological regulator, possibly involved in the maintenance of energy balance. PMID- 25119863 TI - Silver nanoparticles/ibuprofen-loaded poly(L-lactide) fibrous membrane: anti infection and anti-adhesion effects. AB - Infection caused by bacteria is one of the crucial risk factors for tendon adhesion formation. Silver nanoparticles (AgNP)-loaded physical barriers were reported to be effective in anti-infection and anti-adhesion. However, high silver load may lead to kidney and liver damages. This study was designed for Ibuprofen (IBU)-loaded poly(L-lactide) (PLLA) electrospun fibrous membranes containing a low dosage of Ag to evaluate its potential in maintaining suitable anti-infection and good anti-adhesion effects. The in vitro drug release study showed a sustained release of Ag ions and IBU from the membrane. Inferior adherence and proliferation of fibroblasts were found on the Ag4%-IBU4%-loaded PLLA electrospun fibrous membranes in comparison with pure PLLA and 4% Ag-loaded PLLA membranes. In the antibacterial test, all Ag-loaded PLLA electrospun fibrous membranes prevented the adhesion of Staphylococcus aureus and Staphylococcus epidermidis. Taken together, these results demonstrate that Ibuprofen is effective in enhancing the anti-adhesion and anti-proliferation effects of 4% Ag loaded PLLA fibrous membrane. The medical potential of infection reduction and adhesion prevention of Ag4%-IBU4%-loaded PLLA electrospun fibrous membrane deserves to be further studied. PMID- 25119861 TI - Mechanistic understanding of toxicity from nanocatalysts. AB - Nanoparticle-based catalysts, or nanocatalysts, have been applied in various industrial sectors, including refineries, petrochemical plants, the pharmaceutical industry, the chemical industry, food processing, and environmental remediation. As a result, there is an increasing risk of human exposure to nanocatalysts. This review evaluates the toxicity of popular nanocatalysts applied in industrial processes in cell and animal models. The molecular mechanisms associated with such nanotoxicity are emphasized to reveal common toxicity-inducing pathways from various nanocatalysts and the uniqueness of each specific nanocatalyst. PMID- 25119862 TI - Current status of long non-coding RNAs in human cancer with specific focus on colorectal cancer. AB - The latest investigations of long non-coding RNAs (lncRNAs) have revealed their important role in human cancers. LncRNAs are larger than 200 nucleotides in length and fulfill their cellular purpose without being translated into proteins. Though the molecular functions of some lncRNAs have been elucidated, there is still a high number of lncRNAs with unknown or controversial functions. In this review, we provide an overview of different lncRNAs and their role in human cancers. In particular, we emphasize their importance in tumorigenesis of colorectal cancer, the third most common cancer worldwide. PMID- 25119864 TI - Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients refractory to conventional therapy. AB - Allogeneic mesenchymal stem cell transplantation (MSCT) has been shown to be clinically efficacious in the treatment of various autoimmune diseases. Here, we analyzed the role of allogeneic MSCT to induce renal remission in patients with active and refractory lupus nephritis (LN). This is an open-label and single center clinical trial conducted from 2007 to 2010 in which 81 Chinese patients with active and refractory LN were enrolled. Allogeneic bone marrow- or umbilical cord-derived mesenchymal stem cells (MSCs) were administered intravenously at the dose of 1 million cells per kilogram of bodyweight. All patients were then monitored over the course of 12 months with periodic follow-up visits to evaluate renal remission, as well as possible adverse events. The primary outcome was complete renal remission (CR) and partial remission (PR) at each follow-up, as well as renal flares. The secondary outcome included renal activity score, total disease activity score, renal function, and serologic index. During the 12-month follow-up, the overall rate of survival was 95 % (77/81). Totally, 60.5 % (49/81) patients achieved renal remission during 12-month visit by MSCT. Eleven of 49 (22.4 %) patients experienced renal flare by the end of 12 months after a previous remission. Renal activity evaluated by British Isles Lupus Assessment Group (BILAG) scores significantly declined after MSCT (mean +/- SD, from 4.48 +/ 2.60 at baseline to 1.09 +/- 0.83 at 12 months), in parallel with the obvious amelioration of renal function. Glomerular filtration rate (GFR) improved significantly 12 months after MSCT (mean +/- SD, from 58.55 +/- 19.16 to 69.51 +/ 27.93 mL/min). Total disease activity evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores also decreased after treatment (mean +/- SD, from 13.11 +/- 4.20 at baseline to 5.48 +/- 2.77 at 12 months). Additionally, the doses of concomitant prednisone and immunosuppressive drugs were tapered. No transplantation-related adverse event was observed. Allogeneic MSCT resulted in renal remission for active LN patients within 12-month visit, confirming its use as a potential therapy for refractory LN. PMID- 25119866 TI - [Relevance of the current discussion on prioritization for rheumatology]. AB - BACKGROUND: The increase in age-related diseases that can be expected due to demographic changes, the growing medicalization and the medical technological progress with new diagnostic and therapeutic methods, will probably lead to rising health expenditure in the coming years. The resulting financial problems have so far mostly been countered by an increase in health insurance contributions, tax subsidies, rationalization and hidden rationing. The potentials of explicit prioritization processes have so far not been made use of in Germany compared to some other countries where this is already in common use. METHODS: Prioritization in the healthcare system is a procedure of mental clarification and determination of the priority or subordination of certain indications, patient groups or methods with the result of multilevel ranking. Human dignity, equality and solidarity are fundamental values on which prioritization is based. The medical need, the urgency of treatment, the expected medical benefits, the treatment risk, the cost efficiency and the evidence level are criteria towards which prioritization is oriented. RESULTS: Prioritization processes lead to scientifically substantiated care recommendations which support decisions regarding the medically rational, ethically justifiable and economically meaningful use of limited resources. In order to gain broad public acceptance, prioritization guidelines should be developed in a transparent way by democratically justified committees the composition of which still needs to be clarified. Fundamental concepts, cornerstones of the current debate and efforts that have already been made to make progress in this field are presented in summarized form in this article. PMID- 25119865 TI - History of knee injury and MRI-assessed knee structures in middle- and older-aged adults: a cross-sectional study. AB - The aim of this cross-sectional study was to describe the associations between history of knee injury and knee structure using magnetic resonance imaging (MRI). This study included two population-based samples: the Tasmanian Older Adult Cohort (TASOAC) study (n = 430; mean age, 63.0 years; range, 51-79 years; 51 % female) and the Offspring study (n = 372; mean age, 45.0 years; range, 26-61 years; 57.5 % female). In both studies, 1.5 T MRI scans of the right knee were performed to measure bone marrow lesions (BMLs), cartilage volume, tibial bone area, cartilage defects and meniscal pathology. History of knee injury was assessed using a self-administered questionnaire. The association between knee injury and knee structure was determined using multiple linear and log binomial regression models. Nineteen percent of the middle-aged and 12 % of the older adults reported a history of knee injury. In middle-aged adults, BML presence (prevalence ratio (PR) = 1.6 (95 % CI, 1.2; 2.1)), tibial bone area (difference of means (DM) = +86 (+23, +149)) and meniscal extrusion presence (PR = 2.7 (1.1, 6.8)) were significantly higher in those with knee injury. In older adults, cartilage defect presence (PR = 1.3 (1.0, 1.7)), lateral (DM = -265 (-439, -92)) and total tibial (DM = -325 (-600, -51)) cartilage volume, BML presence (PR = 1.4 (1.0, 1.9)) and tibial bone area (DM = +140 (+19, +260)) were significantly associated with knee injury. Meniscal tears showed no significant associations in either cohorts. The association between knee injury and MRI-assessed structural pathology in the knee joint is moderate and appears to be stronger in older adults compared to middle-aged adults. PMID- 25119867 TI - Oleuropein offers cardioprotection in rats with acute myocardial infarction. AB - Myocardial infarction causes a cascade of events, which leads to heart failure, debilitation and death. This study examined possible cardioprotective effect of oleuropein in rats with acute myocardial infarction. Male Sprague-Dawly rats were allocated to five groups: sham, myocardial infarction receiving vehicle, and three myocardial infarction receiving oleuropein at 10, 20, and 30 mg/kg/day for 7 days, and underwent sham operation or coronary ligation. Twenty-four hours later, animals underwent echocardiographic and hemodynamic studies, and infarct areas, serum concentrations of oxidative stress and inflammatory markers were determined. Myocardial infarction group receiving vehicle had significantly lower left ventricular developed and systolic pressures, rate of rise/decrease of left ventricular pressure, stroke volume, ejection fraction and cardiac output, and serum superoxide dismutase and glutathione reductase than those of sham group. Pretreatment with oleuropein prevented the reduction of these variables. Moreover, the group had a significantly higher serum malondialdehyde, interleukin 1beta, TNF-alpha, creatin kinase-MB, and troponin I, lactate dehydrogenase, and infarct area than those of sham group. Pretreatment with oleuropein prevented the increase of these variables. The findings indicate that coronary ligation results in acute myocardial infarction characterized by impaired cardiac function, and oleuropein pretreatment prevented cardiac impairment partly by reducing oxidative stress and release of proinflammatory cytokines. PMID- 25119868 TI - High-density single nucleotide polymorphism (SNP) array mapping in Brassica oleracea: identification of QTL associated with carotenoid variation in broccoli florets. AB - KEY MESSAGE: A high-resolution genetic linkage map of B. oleracea was developed from a B. napus SNP array. The work will facilitate genetic and evolutionary studies in Brassicaceae. A broccoli population, VI-158 * BNC, consisting of 150 F2:3 families was used to create a saturated Brassica oleracea (diploid: CC) linkage map using a recently developed rapeseed (Brassica napus) (tetraploid: AACC) Illumina Infinium single nucleotide polymorphism (SNP) array. The map consisted of 547 non-redundant SNP markers spanning 948.1 cM across nine chromosomes with an average interval size of 1.7 cM. As the SNPs are anchored to the genomic reference sequence of the rapid cycling B. oleracea TO1000, we were able to estimate that the map provides 96 % coverage of the diploid genome. Carotenoid analysis of 2 years data identified 3 QTLs on two chromosomes that are associated with up to half of the phenotypic variation associated with the accumulation of total or individual compounds. By searching the genome sequences of the two related diploid species (B. oleracea and B. rapa), we further identified putative carotenoid candidate genes in the region of these QTLs. This is the first description of the use of a B. napus SNP array to rapidly construct high-density genetic linkage maps of one of the constituent diploid species. The unambiguous nature of these markers with regard to genomic sequences provides evidence to the nature of genes underlying the QTL, and demonstrates the value and impact this resource will have on Brassica research. PMID- 25119869 TI - The detection of a de novo allele of the Glu-1Dx gene in wheat-rye hybrid offspring. AB - KEY MESSAGE: This study provides a link between a de novo gene and novel phenotype in wheat-rye hybrids that can be used as a model for induced de novo genetic variation. Wide hybridization can produce de novo DNA variation that may cause novel phenotypes. However, there is still a lack of specific links between changed genes and novel phenotypes in wide hybrids. The well-studied high molecular-weight glutenin subunit (HMW-GS) genes in tribe Triticeae provide a useful model for addressing this issue. In this study, we investigated the feasibility of a wheat-rye hybridization method for inducing de novo phenotypes using the Glu-1Dx2.2 subunit as an example. We developed three hexaploid wheat lines with normal fertility and a Glu-1Dx2.2 variant, named Glu-1Dx2.2 (v) , derived from three F1 hybrids. The wild-type Glu-1Dx2.2 has two direct repeats of 295 bp length separated by an intervening 101 bp in its central repetitive region. In the mutant Glu-1Dx2.2 (v) , one copy of the repeats and the intervening sequence were deleted, probably through homology-dependent illegitimate recombination (IR). This study provides a direct link between a de novo allele and novel phenotype. Our results indicate that the wheat-rye method may be a useful tool to induce de novo genetic variations that broaden the genetic diversity for wheat improvement. PMID- 25119870 TI - Next generation genetic mapping of the Ligon-lintless-2 (Li2) locus in upland cotton (Gossypium hirsutum L.). AB - KEY MESSAGE: Mapping-by-sequencing and novel subgenome-specific SNP markers were used to fine map the Ligon-lintless 2 ( Li 2 ) short-fiber gene in tetraploid cotton. These methodologies will accelerate gene identification in polyploid species. Next generation sequencing offers new ways to identify the genetic mechanisms that underlie mutant phenotypes. The release of a reference diploid Gossypium raimondii (D5) genome and bioinformatics tools to sort tetraploid reads into subgenomes has brought cotton genetic mapping into the genomics era. We used multiple high-throughput sequencing approaches to identify the relevant region of reference sequence and identify single nucleotide polymorphisms (SNPs) near the short-fiber mutant Ligon-lintless 2 (Li 2) gene locus. First, we performed RNAseq on 8-day post-anthesis (DPA) fiber cells from the Li 2 mutant and its wild type near isogenic line (NIL) Gossypium hirsutum cv. DP5690. We aligned sequence reads to the D5 genome, sorted the reads into A and D subgenomes with PolyCat and called SNPs with InterSNP. We then identified SNPs that would result in non synonymous substitutions to amino acid sequences of annotated genes. This step allowed us to identify a 1-Mb region with 24 non-synonymous SNPs, representing the introgressed region that differentiates Li 2 from its NIL. Next, we sequenced total DNA from pools of F2 plants, using a super bulked segregant analysis sequencing (sBSAseq) approach. The sBSAseq predicted 82 non-synonymous SNPs among 3,494 SNPs in a 3-Mb region that includes the region identified by RNAseq. We designed subgenome-specific SNP markers and tested them in an F2 population of 1,733 individuals to construct a genetic map. Our resulting genetic interval contains only one gene, an aquaporin, which is highly expressed in wild-type fibers and is significantly under-expressed in elongating Li 2 fiber cells. PMID- 25119871 TI - An extensive analysis of the African rice genetic diversity through a global genotyping. AB - KEY MESSAGE: We present here the first curated collection of wild and cultivated African rice species. For that, we designed specific SNPs and were able to structure these very low diverse species. Oryza glaberrima, the cultivated African rice, is endemic from Africa. This species and its direct ancestor, O. barthii, are valuable tool for improvement of Asian rice O. sativa in terms of abiotic and biotic stress resistance. However, only a few limited studies about the genetic diversity of these species were performed. In the present paper, and for the first time at such extend, we genotyped 279 O. glaberrima, selected both for their impact in current breeding and for their geographical distribution, and 101 O. barthii, chosen based on their geographic origin, using a set of 235 SNPs specifically designed for African rice diversity. Using those data, we were able to structure the individuals from our sample in three populations for O. barthii, related to geography, and two populations in O. glaberrima; these two last populations cannot be linked however to any currently phenotyped trait. Moreover, we were also able to identify misclassification in O. glaberrima as well as in O. barthii and identified new form of O. sativa from the set of African varieties. PMID- 25119872 TI - Gene-based SNP discovery and genetic mapping in pea. AB - KEY MESSAGE: Gene-based SNPs were identified and mapped in pea using five recombinant inbred line populations segregating for traits of agronomic importance. Pea (Pisum sativum L.) is one of the world's oldest domesticated crops and has been a model system in plant biology and genetics since the work of Gregor Mendel. Pea is the second most widely grown pulse crop in the world following common bean. The importance of pea as a food crop is growing due to its combination of moderate protein concentration, slowly digestible starch, high dietary fiber concentration, and its richness in micronutrients; however, pea has lagged behind other major crops in harnessing recent advances in molecular biology, genomics and bioinformatics, partly due to its large genome size with a large proportion of repetitive sequence, and to the relatively limited investment in research in this crop globally. The objective of this research was the development of a genome-wide transcriptome-based pea single-nucleotide polymorphism (SNP) marker platform using next-generation sequencing technology. A total of 1,536 polymorphic SNP loci selected from over 20,000 non-redundant SNPs identified using deep transcriptome sequencing of eight diverse Pisum accessions were used for genotyping in five RIL populations using an Illumina GoldenGate assay. The first high-density pea SNP map defining all seven linkage groups was generated by integrating with previously published anchor markers. Syntenic relationships of this map with the model legume Medicago truncatula and lentil (Lens culinaris Medik.) maps were established. The genic SNP map establishes a foundation for future molecular breeding efforts by enabling both the identification and tracking of introgression of genomic regions harbouring QTLs related to agronomic and seed quality traits. PMID- 25119874 TI - A study on usefulness evaluation of SUV measured in mini-PACS for each one of PET/CT equipment. AB - To save and analyze the data from a positron emission tomography/computed tomography (PET/CT) scan, it is sometimes important to use a server away from the workstation of the equipment or to install and operate mini-picture archiving and communication system (PACS). Mini-PACS was developed to save the data from a scan and measure the standard uptake value (SUV) in PACS that could be measured only in PET/CT equipment manufactured by many companies. Against this background, this study examined whether the SUV measured in PET/CT equipment was the same value in mini-PACS. This study evaluated Biograph 16 and Biograph 40 manufactured by SIEMENS and Discovery Ste 8 manufactured by GE, all of which are installed in this hospital. The SUV of the aorta of 30 patients, who had undergone an (18)F FDG whole body PET scan in the period from February to October 2012, was measured at the height of the liver and mediastinum. In the mini-PACS program, the SUV was also measured and analyzed in an image with the same phase. According to the study results, the coefficient of the SUV of the liver in PET/CT equipment and mini-PACS was 0.99, 0.98, and 0.64 in Biograph 16, Biograph 40, and Discovery Ste 8, respectively, where the coefficient of the SUV of aorta was 0.98, 0.98, and 0.66 in Biograph 16, Biograph 40, and Discovery Ste 8, showing a positive correlation in all equipment. PMID- 25119873 TI - A high-resolution linkage map of the Rfd1, a restorer-of-fertility locus for cytoplasmic male sterility in radish (Raphanus sativus L.) produced by a combination of bulked segregant analysis and RNA-Seq. AB - KEY MESSAGE: We utilized a combination of BSA and RNA-Seq to identify SNPs linked to the Rfd1 locus, a restorer-of-fertility gene in radish. A high-density linkage map was constructed using this approach. Male fertility of cytoplasmic male sterility conditioned by the Dongbu cytoplasmic and genic male-sterility cytoplasm can be restored by a restorer-of-fertility locus, Rfd1, in radish. To construct a high-density linkage map and to identify a candidate gene for the Rfd1 locus, bulked segregant analysis and RNA-seq approaches were combined. A total of 26 and 28 million reads produced from male-fertile and male-sterile bulked RNA were mapped to the radish reference unigenes. After stringent screening of SNPs, 327 reliable SNPs of 109 unigenes were selected. Arabidopsis homologs for 101 of the 109 genes were clustered around the 4,000 kb region of Arabidopsis chromosome 3, which was syntenic to the Rfd1 flanking region. Since the reference unigene set was incomplete, the contigs were de novo assembled to identify 134 contigs harboring SNPs. Most of SNP-containing contigs were also clustered on the same syntenic region in Arabidopsis chromosome. A total of 21 molecular markers positioned within a 2.1 cM interval including the Rfd1 locus were developed, based on the selected unigenes and contigs. A segregating population consisting of 10,459 individuals was analyzed to identify recombinants containing crossovers within this interval. A total of 284 identified recombinants were then used to construct a high-density map, which delimited the Rfd1 locus into an 83-kb syntenic interval of Arabidopsis chromosome 3. Since no candidate gene, such as a pentatricopeptide repeat (PPR)-coding gene, was found in this interval, 231 unigenes and 491 contigs containing putative PPR motifs were analyzed further, but no PPR gene in linkage disequilibrium with the Rfd1 locus could be found. PMID- 25119875 TI - The effect of caste and reproductive state on the chemistry of the cephalic labial glands secretion of Bombus terrestris. AB - The cephalic labial glands are well developed in many bee species. In bumble bee males, they cover most of the head volume, and their secretion is used in marking reproductive territories and attracting virgin queens. In females, however, they are poorly studied. Here, we present chemical analyses of their secretion in queens and workers of Bombus terrestris under various social conditions. The secretion revealed a context-dependent composition with sterile females possessing large amounts of fatty acid dodecyl esters, ranging from dodecyl hexanoate to dodecyl oleate, compared to small amounts in fertile females. Significant reduction in the dodecyl esters also was found in queens at the competition phase, where worker reproduction, aggression, and gyne differentiation occur. The exclusive production of esters by sterile individuals also is typical of Dufour's gland secretion in this species, albeit in this case these are octyl rather than dodecyl esters, and the differences between sterile and fertile individuals are qualitative rather than quantitative. We propose that the labial gland esters provide yet another signal of reproductive inactivity. In virgin queens, it may signal that egg laying is deferred to the next season, while in workers it reinforces the message "I am sterile and out of the reproductive competition". Whether the reduction in dodecyl esters in fertile queens as a function of colony social development is involved in regulating gyne production and the onset of the competition phase is yet to be deciphered. PMID- 25119876 TI - A pilot study of a new spectrophotometry device to measure tissue oxygen saturation. AB - Tissue oxygen saturation (SO2) measurements have the potential for far wider use than at present but are limited by device availability and portability for many potential applications. A device based on a small, low-cost general-purpose spectrophotometer (the Harrison device) might facilitate wider use. The aim of this study was to compare the Harrison device with a commercial instrument, the LEA O2C.Measurements were carried out on the forearm and finger of 20 healthy volunteers, using a blood pressure cuff on the upper arm to induce different levels of oxygenation. Repeatability of both devices was assessed, and the Bland Altman method was used to assess agreement between them.The devices showed agreement in overall tracking of changes in SO2. Test-retest agreement for the Harrison device was worse than for O2C, with SD repeatability of 10.6% (forearm) or 18.6% (finger). There was no overall bias between devices, but mean (SD) difference of 1.2 (11.8%) (forearm) or 4.4 (11.5%) (finger) were outside of a clinically acceptable range.Disagreements were attributed to the stability of the Harrison probe and the natural SO2 variations across the skin surface increasing the random error. Therefore, though not equivalent to the LEA O2C, a probe redesign and averaged measurements may help establish the Harrison device as a low cost alternative. PMID- 25119877 TI - Fecal impaction. AB - Fecal impaction (FI) is a common and potentially serious medical condition that occurs in all age groups. Children, incapacitated patients, and the institutionalized elderly are considered the highest at-risk populations. FI usually occurs in the setting of chronic or severe constipation, anatomic anorectal abnormalities, and neurogenic or functional gastrointestinal disorders. Generally, FI is a preventable disorder, and early recognition is important, as it is associated with increased morbidity, mortality, and high health care costs. Evaluation with a careful history and physical examination, in conjunction with radiologic imaging, such as an acute abdominal series or computed tomography (CT), is imperative. Prompt identification and treatment minimize the risk of complications attributable to FI, which may include bowel obstruction leading to stercoral ulcer, perforation, peritonitis, or cardiopulmonary collapse with hemodynamic instability. Treatment options include manual fragmentation and extraction of the fecal mass, distal colonic cleansing using enemas and rectal lavage with the aid of a sigmoidoscope, and/or using water-soluble contrast media such as Gastrografin to both identify the extent of the impaction and aid in cleansing and removal. Surgical resection of the involved colon or rectum is reserved for peritonitis resulting from bowel perforation. Since recurrence is common, implementing preventive measures such as increasing daily water and fiber intake, limiting medications that decrease colonic motility, using secretagogues or prokinetic agents, and treating underlying anatomic defects are highly important. PMID- 25119878 TI - MicroRNAs as modulators and biomarkers of inflammatory and neuropathic pain conditions. AB - The post-transcriptional regulator molecules, microRNAs, have emerged as important biomarkers and modulators of numerous pathophysiological processes including oncogenesis and cardiovascular diseases. Recently, a significant number of dysregulations in microRNAs have been reported in patients suffering from painful disorders such as complex regional pain syndrome, cystitis-induced chronic pain and irritable bowel disorder, in both affected tissues and the circulation. Moreover, microRNAs are known to be involved in pain processing based on several recent findings in animal models of inflammatory and neuropathic pain. The basis of this review was to cover and summarize available articles in English encompassing "microRNA and pain". In animal pain models widespread microRNA modulation is present and manifests on multiple levels i.e.: the dorsal root ganglia, the spinal dorsal horn and the brain. Numerous functional in vivo studies have found that dysregulated microRNAs are involved in the post transcriptional modulation of genes implicated in pain generation and maintenance. Lastly, a few animal studies have delivered promising results as to the possibility of applying microRNAs as therapeutics to alleviate established pain and several clinical studies have highlighted the potential in applying microRNAs as biomarkers in painful conditions such as complex regional pain syndrome and fibromyalgia. This review briefly introduces the basics of microRNAs, their biogenesis and function, and mainly focuses on the recent advances made in understanding the role of microRNAs in relation to pain processing and painful conditions. It also provides an overview of widely diverse methodological approaches and results with a potential for future implications of microRNAs in the diagnosis and treatment of pain. PMID- 25119879 TI - The oral commensal Streptococcus mitis shows a mixed memory Th cell signature that is similar to and cross-reactive with Streptococcus pneumoniae. AB - BACKGROUND: Carriage of and infection with Streptococcus pneumoniae is known to predominantly induce T helper 17 (Th17) responses in humans, but the types of Th cells showing reactivity towards commensal streptococci with low pathogenic potential, such as the oral commensals S. mitis and S. salivarius, remain uncharacterized. METHODS: Memory CD4(+) T helper (Th) cell subsets were isolated from healthy human blood donors according to differential expression of chemokine receptors, expanded in vitro using polyclonal stimuli and characterized for reactivity against different streptococcal strains. RESULTS: Th cells responding to S. mitis, S. salivarius and S. pneumoniae were predominantly in a CCR6(+)CXCR3(+) subset and produced IFN-gamma, and in a CCR6(+)CCR4(+) subset and produced IL-17 and IL-22. Frequencies of S. pneumoniae-reactive Th cells were higher than frequencies of S. mitis- and S. salivarius-specific Th cells. S. mitis and S. pneumoniae isogenic capsule knock-out mutants and a S. mitis mutant expressing the serotype 4 capsule of S. pneumoniae showed no different Th cell responses as compared to wild type strains. S. mitis-specific Th17 cells showed cross-reactivity with S. pneumoniae. CONCLUSIONS: As Th17 cells partly control clearance of S. pneumoniae, cross-reactive Th17 cells that may be induced by commensal bacterial species may influence the immune response, independent of capsule expression. PMID- 25119880 TI - Atrial fibrillation as a marker of occult cancer. AB - BACKGROUND: Recent studies suggest that cancer increases risk of atrial fibrillation. Whether atrial fibrillation is a marker for underlying occult cancer is unknown. METHODS: We conducted a cohort study (1980-2011) of all Danish patients with new-onset atrial fibrillation. To examine cancer risk, we computed absolute risk at 3 months and standardized incidence ratios (SIRs) by comparing observed cancer incidence among patients newly diagnosed with atrial fibrillation with that expected based on national cancer incidence during the period. RESULTS: Median follow-up time was 3.4 years among 269 742 atrial fibrillation patients. Within 3 months of follow-up, 6656 cancers occurred (absolute risk, 2.5%; 95% confidence intervals [CI], 2.4%-2.5%) versus 1302 expected, yielding a SIR of 5.11; 95% CI, 4.99-5.24. Associations were particularly strong for cancers of the lung, kidney, colon, ovary, and for non-Hodgkin's lymphoma. The SIR within 3 months of follow-up was 7.02; 95% CI, 6.76-7.28 for metastatic and 3.53; 95% CI, 3.38-3.68 for localized cancer. Beyond 3 months of follow-up, overall cancer risk was modestly increased (SIR, 1.13; 95% CI, 1.12-1.15). CONCLUSION: Patients with new-onset atrial fibrillation had a markedly increased relative risk of a cancer diagnosis within the next three months, however, corresponding absolute risk was small. PMID- 25119882 TI - A hybrid model for predicting the prevalence of schistosomiasis in humans of Qianjiang City, China. AB - BACKGROUNDS/OBJECTIVE: Schistosomiasis is still a major public health problem in China, despite the fact that the government has implemented a series of strategies to prevent and control the spread of the parasitic disease. Advanced warning and reliable forecasting can help policymakers to adjust and implement strategies more effectively, which will lead to the control and elimination of schistosomiasis. Our aim is to explore the application of a hybrid forecasting model to track the trends of the prevalence of schistosomiasis in humans, which provides a methodological basis for predicting and detecting schistosomiasis infection in endemic areas. METHODS: A hybrid approach combining the autoregressive integrated moving average (ARIMA) model and the nonlinear autoregressive neural network (NARNN) model to forecast the prevalence of schistosomiasis in the future four years. Forecasting performance was compared between the hybrid ARIMA-NARNN model, and the single ARIMA or the single NARNN model. RESULTS: The modelling mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of the ARIMA-NARNN model was 0.1869 * 10(-4), 0.0029, 0.0419 with a corresponding testing error of 0.9375 * 10(-4), 0.0081, 0.9064, respectively. These error values generated with the hybrid model were all lower than those obtained from the single ARIMA or NARNN model. The forecasting values were 0.75%, 0.80%, 0.76% and 0.77% in the future four years, which demonstrated a no-downward trend. CONCLUSION: The hybrid model has high quality prediction accuracy in the prevalence of schistosomiasis, which provides a methodological basis for future schistosomiasis monitoring and control strategies in the study area. It is worth attempting to utilize the hybrid detection scheme in other schistosomiasis-endemic areas including other infectious diseases. PMID- 25119881 TI - Nasal sensitization with ragweed pollen induces local-allergic-rhinitis-like symptoms in mice. AB - Recently, the concept of local allergic rhinitis (LAR) was established, namely rhinitis symptoms with local IgE production and negative serum antigen-specific IgE. However, the natural course of LAR development and the disease pathogenesis is poorly understood. This study investigated the pathophysiology of mice with allergic rhinitis that initially sensitized with ragweed pollen through the nasal route. Mice were nasally administrated ragweed pollen over consecutive days without prior systemic immunization of the allergen. Serial nasal sensitization of ragweed pollen induced an allergen-specific increase in sneezing, eosinophilic infiltration, and the production of local IgE by day 7, but serum antigen specific IgE was not detected. Th2 cells accumulated in nose and cervical lymph nodes as early as day 3. These symptoms are characteristic of human LAR. Continual nasal exposure of ragweed pollen for 3 weeks resulted in the onset of classical AR with systemic atopy and adversely affected lung inflammation when the allergen was instilled into the lung. Fcer1a(-/-) mice were defective in sneezing but developed normal eosinophilic infiltration. Contrary, Rag2(-/-) mice were defective in both sneezing and eosinophilic infiltration, suggesting that T cells play a central role in the pathogenesis of the disease. These observations demonstrate nasal allergen sensitization to non-atopic individuals can induce LAR. Because local Th2 cell accumulation is the first sign and Th2 cells have a central role in the disease, a T-cell-based approach may aid the diagnosis and treatment of LAR. PMID- 25119883 TI - Engineered hyperactive integrase for concerted HIV-1 DNA integration. AB - The DNA cutting and joining reactions of HIV-1 integration are catalyzed by integrase (IN), a viral protein that functions as a tetramer bridging the two viral DNA ends (intasome). Two major obstacles for biochemical and structural studies of HIV-1 intasomes are 1) the low efficiency of assembly with oligonucleotide DNA substrates, and 2) the non-specific aggregation of both intasomes and free IN in the reaction mixture. By fusing IN with a small non specific DNA binding protein, Sulfolobus solfataricus chromosomal protein Sso7d (PDB: 1BNZ), we have engineered a highly soluble and hyperactive IN. Unlike wild type IN, it efficiently catalyzes intasome assembly and concerted integration with oligonucleotide DNA substrates. The fusion IN protein also functions to integrate viral reverse transcripts during HIV-infection. The hyperactive HIV-1 IN may assist in facilitating future biochemical and structural studies of HIV-1 intasomes. Understanding the mechanistic basis of the Sso7d-IN fusion protein could provide insight into the factors that have hindered biophysical studies of wild-type HIV-1 IN and intasomes. PMID- 25119884 TI - Persistent release of IL-1s from skin is associated with systemic cardio-vascular disease, emaciation and systemic amyloidosis: the potential of anti-IL-1 therapy for systemic inflammatory diseases. AB - The skin is an immune organ that contains innate and acquired immune systems and thus is able to respond to exogenous stimuli producing large amount of proinflammatory cytokines including IL-1 and IL-1 family members. The role of the epidermal IL-1 is not limited to initiation of local inflammatory responses, but also to induction of systemic inflammation. However, association of persistent release of IL-1 family members from severe skin inflammatory diseases such as psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and desmoglein-1 deficiency syndrome with diseases in systemic organs have not been so far assessed. Here, we showed the occurrence of severe systemic cardiovascular diseases and metabolic abnormalities including aberrant vascular wall remodeling with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty tissue loss and systemic amyloid deposition in multiple organs with liver and kidney dysfunction in mouse models with severe dermatitis caused by persistent release of IL-1s from the skin. These morbid conditions were ameliorated by simultaneous administration of anti-IL-1alpha and IL-1beta antibodies. These findings may explain the morbid association of arteriosclerosis, heart involvement, amyloidosis and cachexia in severe systemic skin diseases and systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy for systemic inflammatory diseases. PMID- 25119885 TI - Large artery stiffness and carotid intima-media thickness in relation to markers of calcium and bone mineral metabolism in African women older than 46 years. AB - Vascular calcification and cardiovascular diseases have been associated with altered bone metabolism. We explored the relationships of arterial pressures and carotid intima-media thickness (CIMT) with parathyroid hormone, 25 hydroxycholecalciferol and their ratio (PTH:25(OH)D3) as well as a marker of bone resorption (CTX) in lean and overweight/obese African women. A population of 434 African women older than 46 years was divided into lean and overweight/obese groups. We assessed brachial blood pressure, central pulse pressure (cPP) and CIMT, and determined PTH, 25(OH)D3 and CTX concentrations. Overweight/obese women had elevated PTH and PTH:25(OH)D3 compared with lean women (both P<0.001), whereas lean women had higher CTX (P<0.001). Single, partial and multiple regression analyses indicated that, in lean women CIMT was independently associated with PTH:25(OH)D3 (R(2)=0.22; beta=0.26; P=0.003), whereas in obese women cPP was associated with both PTH:25(OH)D3 (R2=0.20; beta=0.17; P=0.017) and CTX (R2=0.20; beta=0.17; P=0.025). In conclusion, we found that in African women with increased adiposity, cPP (as a surrogate measure of arterial stiffness), was positively associated with alterations in bone metabolism and calciotropic hormones, whereas CIMT of lean women was positively associated with PTH:25(OH)D3. Our results suggest that alterations in bone and calcium metabolism may contribute to arterial calcification in older African women. PMID- 25119886 TI - Association between undiagnosed hypertension and microalbuminuria in South Asians without known diabetes. AB - Data suggest increased rates of chronic kidney disease (CKD) in those with undiagnosed hypertension (HTN). Our study aimed to determine the prevalence of CKD in undiagnosed hypertensives in a previously unreported subgroup of individuals of South Asian ethnicity. We analysed data from subjects in the ADDITION-Leicester study, a UK based multiethnic, community diabetes screening study. Standard definitions included: HTN-mean recorded BP of ?140/90 mm Hg, CKD stage 3 and above-estimated glomerular filtration rate (eGFR) <60 ml min(-1) per 1.73 m2 and microalbuminuria as albumin creatinine ratio ?3 mg mmol(-1). Logistic regression was performed with age, gender and body mass index (kg m(-2)) as co variates. 6082 individuals (52.5% female, mean age, 57.2 years; White European, 77.8% and South Asian, 22.0%), 31.1% had undiagnosed HTN. Overall, individuals with undiagnosed HTN compared with normotensives had an odds ratio for microalbuminuria of 2.24 (95% confidence interval (CI): 1.72-2.94). For South Asians, the odds ratio was 3.81. (95% CI: 2.24-6.47) for microalbuminuria with a trend towards an eGFR<60 ml min(-1) per 1.73 m2. Future studies should consider intensified screening for HTN to refine the population suitable for CKD screening, particularly in the South Asian ethnic group. PMID- 25119887 TI - Accelerated analysis of three-dimensional blood flow of the thoracic aorta in stroke patients. AB - To test if new software accelerates analysis of in vivo acquired 4D flow MRI data. Respiration-gated and ECG-synchronized 4D flow MRI of the aorta was performed in 20 stroke patients using a routine 3-Tesla MRI system (TIMTRIO, Siemens, Germany). 3D blood flow data was processed by one experienced observer using new (A = MEVISFlow) and widely-used software (B = EnSight + Velomap /FlowTool). Evaluation included: inter-/intra-observer variability of software A and inter-software comparison regarding (1) blood flow quantification (total /peak flow) and (2) flow visualisation, plus (3) measurement of the time required for visualization and quantification of data (software A&B). (1) Inter-/intra observer agreement of software A (mean difference <=5.2 and <=0.9 %, respectively) and inter-software agreement (mean difference <= 2.2 %) was high with high correlation of peak and total blood flow (r >= 0.74; p < 0.001 and r >= 0.91; p < 0.001). (2) Comparison of blood flow visualization showed substantial agreement (kappa >= 0.68). (3) Data-analysis was three times faster when using software A [18:10 (+/-1:29) vs. 58:30 (+/-5:28) min; p < 0.0001]. Acceleration of blood flow quantification and visualisation using new software strongly facilitates future applications of 4D flow MRI and thus enables its usage in larger patient cohorts in clinical research and routine. PMID- 25119888 TI - High-pitch prospective ECG-triggered helical coronary computed tomography angiography in clinical practice: image quality and radiation dose. AB - High-pitch prospective ECG-triggered helical (PTH) protocols for coronary computed tomography angiography (CCTA) have demonstrated adequate image quality (IQ) in small-scaled studies and highly selected patients. Clinical applicability in a general clinical population is uncertain. This study evaluated the implementation of a PTH protocol in a routine clinical cohort, focusing on IQ and radiation dose. The local scientific board approved the retrospective analysis and all patients signed an informed consent statement for usage of their data. In consecutive patients suspected of coronary artery disease CCTA was performed using a dual source 128-slice scanner. All patients with a regular heart rate <65 bpm underwent a PTH CCTA. IQ for each coronary segment was graded (1 = absence of artifacts to 4 = non-evaluable). In 664 (80.4 %) of 826 included patients [mean age +/- standard deviation (SD) 57 +/- 11, 65 % female, mean body mass index (BMI) +/- SD 27 +/- 9 kg m(-2)] PTH CCTA was acquired whereas in 162 (19.6 %) a non-PTH sequence was used. Reasons for not performing a PTH protocol were persistent high heart rate (41.6 %) or heart rate irregularity (58.4 %). Mean +/- SD heart rates for PTH and non-PTH CCTA were 55 +/- 5 and 65 +/- 9 bpm, respectively, p < 0.001. In the PTH group 92 % of the segments were of diagnostic quality (score 1-3), versus 87 % in the non-PTH group (p = 0.055). Per patient, mean IQ score was 1.19 and 1.21 respectively (lower is better; p = 0.012). Effective dose (including topogram, test bolus, and coronary calcium score), as calculated with a conversion factor of 0.014 mSv mGy(-1) cm(-1) was 1.6 +/- 0.6 and 4.7 +/- 2.6 mSv for the PTH and the non-PTH group respectively, (p < 0.001). Performing high-pitch PTH sequences on a routine basis is feasible in the majority of patients with high IQ and significant reduction in radiation dose. PMID- 25119889 TI - Computed tomography for planning and postoperative imaging of transvenous mitral annuloplasty: first experience in an animal model. AB - To investigate the use of computed tomography (CT) to measure the mitral valve annulus size before implantation of a percutaneous mitral valve annuloplasty device in an animal trial. Seven domestic pigs underwent CT before and after implantation of a CardiobandTM (a percutaneously implantable mitral valve annuloplasty device) with a second-generation 128-section dual-source CT machine. Implantation of the CardiobandTM was performed in a standard fashion according to a protocol. Animals were sacrificed afterwards and the hearts explanted. The CardiobandTM was found to be adequately implanted in all animals, with no anchor dehiscence and no damage of the circumflex artery (CX) or the coronary sinus (CS). The correct length of the band as chosen according to the length of the posterior mitral annulus measured in CT before implantation was confirmed in gross examination in all animals. The device did not result in a metal artifact related degradation of image quality. The closest distance from the closest anchor to the CX was 2.1 +/- 0.7 mm in diastole and 1.6 +/- 0.5 mm systole. Mitral annulus distance to the CS was 6.4 +/- 1.3 mm in diastole and 7.7 +/- 1.1 mm in systole. CT visualization and measurement of the mitral valve annulus dimensions is feasible and can become the imaging method of choice for procedure planning of CardiobandTM implantations or other transcatheter mitral annuloplasty devices. PMID- 25119891 TI - Annual report SWEDEHEART 2012. PMID- 25119892 TI - Characteristics of childbearing women, obstetrical interventions and preterm delivery: a comparison of the US and France. AB - Preterm delivery rates have remained consistently higher in the US than France, but the reasons for this excess remain poorly understood. We examined if differences in socio-demographic risk factors or more liberal use of obstetrical interventions contributed to higher rates in the US. Data on singleton live births in 1995, 1998 and 2003 from US birth certificates and the French National Perinatal Survey were used to analyze preterm delivery rate by maternal characteristics (age, parity, marital status, education, race (US)/nationality (France), prenatal care and smoking). We distinguished between preterm deliveries with a cesarean or a labor induction and those without these interventions. Unadjusted and adjusted risk ratios (RR) for the US compared to France were estimated using log-binomial regression. Preterm delivery rates were 7.9 % in the US and 4.7 % in France (risk ratio [RR] = 1.7, 95 % confidence interval [CI] 1.6 1.8). The US had more teen mothers and late entry to prenatal care, but fewer women smoked, although adjustment for these and other confounders did not reduce RR (1.8, 95 % CI 1.7-1.9). Preterm delivery rates associated with labor induction or cesarean were 3.3 % in the US and 2.1 % in France (RR 1.6, 95 % CI 1.5-1.7); the corresponding rates for preterm delivery without these interventions were 4.5 and 2.5 % (RR 1.8, 95 % CI 1.7-1.9), respectively. Key socio-demographic risk factors and more obstetric intervention do not explain higher US preterm delivery rates. Avenues for future research include the impact of universal access to health services (universal health insurance?) on health care quality and the association between more generous social policies, stress and the risks of preterm delivery. PMID- 25119890 TI - The nuclear envelope: an intriguing focal point for neurogenetic disease. AB - Mutations in genes encoding nuclear envelope proteins cause a wide range of inherited diseases, many of which are neurological. We review the genetic causes and what little is known about pathogenesis of these nuclear envelopathies that primarily affect striated muscle, peripheral nerve and the central nervous system. We conclude by providing examples of experimental therapeutic approaches to these rare but important neuromuscular diseases. PMID- 25119893 TI - Assessing strategies for heart failure with preserved ejection fraction at the outpatient clinic. AB - BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is the most common form of heart failure (HF), its diagnosis being a challenge to the outpatient clinic practice. OBJECTIVE: To describe and compare two strategies derived from algorithms of the European Society of Cardiology Diastology Guidelines for the diagnosis of HFPEF. METHODS: Cross-sectional study with 166 consecutive ambulatory patients (67.9+/-11.7 years; 72% of women). The strategies to confirm HFPEF were established according to the European Society of Cardiology Diastology Guidelines criteria. In strategy 1 (S1), tissue Doppler echocardiography (TDE) and electrocardiography (ECG) were used; in strategy 2 (S2), B-type natriuretic peptide (BNP) measurement was included. RESULTS: In S1, patients were divided into groups based on the E/E'ratio as follows: GI, E/E'> 15 (n = 16; 9%); GII, E/E'8 to 15 (n = 79; 48%); and GIII, E/E'< 8 (n = 71; 43%). HFPEF was confirmed in GI and excluded in GIII. In GII, TDE [left atrial volume index (LAVI) >= 40 mL/m2; left ventricular mass index LVMI) > 122 for women and > 149 g/m2 for men] and ECG (atrial fibrillation) parameters were assessed, confirming HFPEF in 33 more patients, adding up to 49 (29%). In S2, patients were divided into three groups based on BNP levels. GI (BNP > 200 pg/mL) consisted of 12 patients, HFPEF being confirmed in all of them. GII (BNP ranging from 100 to 200 pg/mL) consisted of 20 patients with LAVI > 29 mL/m2, or LVMI >= 96 g/m2 for women or >= 116 g/m2 for men, or E/E'>= 8 or atrial fibrillation on ECG, and the diagnosis of HFPEF was confirmed in 15. GIII (BNP < 100 pg/mL) consisted of 134 patients, 26 of whom had the diagnosis of HFPEF confirmed when GII parameters were used. Measuring BNP levels in S2 identified 4 more patients (8%) with HFPEF as compared with those identified in S1. CONCLUSION: The association of BNP measurement and TDE data is better than the isolated use of those parameters. BNP can be useful in identifying patients whose diagnosis of HF had been previously excluded based only on TDE findings. PMID- 25119894 TI - Ivabradine improves heart rate variability in patients with nonischemic dilated cardiomyopathy. AB - BACKGROUND: Ivabradine is a novel specific heart rate (HR)-lowering agent that improves event-free survival in patients with heart failure (HF). OBJECTIVES: We aimed to evaluate the effect of ivabradine on time domain indices of heart rate variability (HRV) in patients with HF. METHODS: Forty-eight patients with compensated HF of nonischemic origin were included. Ivabradine treatment was initiated according to the latest HF guidelines. For HRV analysis, 24-h Holter recording was obtained from each patient before and after 8 weeks of treatment with ivabradine. RESULTS: The mean RR interval, standard deviation of all normal to normal RR intervals (SDNN), the standard deviation of 5-min mean RR intervals (SDANN), the mean of the standard deviation of all normal-to-normal RR intervals for all 5-min segments (SDNN index), the percentage of successive normal RR intervals exceeding 50 ms (pNN50), and the square root of the mean of the squares of the differences between successive normal to normal RR intervals (RMSSD) were low at baseline before treatment with ivabradine. After 8 weeks of treatment with ivabradine, the mean HR (83.6 +/- 8.0 and 64.6 +/- 5.8, p < 0.0001), mean RR interval (713 +/- 74 and 943 +/- 101 ms, p < 0.0001), SDNN (56.2 +/- 15.7 and 87.9 +/- 19.4 ms, p < 0.0001), SDANN (49.5 +/- 14.7 and 76.4 +/- 19.5 ms, p < 0.0001), SDNN index (24.7 +/- 8.8 and 38.3 +/- 13.1 ms, p < 0.0001), pNN50 (2.4 +/- 1.6 and 3.2 +/- 2.2 %, p < 0.0001), and RMSSD (13.5 +/- 4.6 and 17.8 +/- 5.4 ms, p < 0.0001) substantially improved, which sustained during both when awake and while asleep. CONCLUSION: Our findings suggest that treatment with ivabradine improves HRV in nonischemic patients with HF. PMID- 25119895 TI - Left atrial volume index and prediction of events in acute coronary syndrome: Solar Registry. AB - BACKGROUND: According to some international studies, patients with acute coronary syndrome (ACS) and increased left atrial volume index (LAVI) have worse long-term prognosis. However, national Brazilian studies confirming this prediction are still lacking. OBJECTIVE: To evaluate LAVI as a predictor of major cardiovascular events (MCE) in patients with ACS during a 365-day follow-up. METHODS: Prospective cohort of 171 patients diagnosed with ACS whose LAVI was calculated within 48 hours after hospital admission. According to LAVI, two groups were categorized: normal LAVI (<= 32 mL/m2) and increased LAVI (> 32 mL/m2). Both groups were compared regarding clinical and echocardiographic characteristics, in and out-of-hospital outcomes, and occurrence of ECM in up to 365 days. RESULTS: Increased LAVI was observed in 78 patients (45%), and was associated with older age, higher body mass index, hypertension, history of myocardial infarction and previous angioplasty, and lower creatinine clearance and ejection fraction. During hospitalization, acute pulmonary edema was more frequent in patients with increased LAVI (14.1% vs. 4.3%, p = 0.024). After discharge, the occurrence of combined outcome for MCE was higher (p = 0.001) in the group with increased LAVI (26%) as compared to the normal LAVI group (7%) [RR (95% CI) = 3.46 (1.54-7.73) vs. 0.80 (0.69-0.92)]. After Cox regression, increased LAVI increased the probability of MCE (HR = 3.08, 95% CI = 1.28-7.40, p = 0.012). CONCLUSION: Increased LAVI is an important predictor of MCE in a one-year follow-up. PMID- 25119896 TI - Haplotype analysis of interleukin-10 gene promoter polymorphisms in chronic hepatitis C infection: a case control study. AB - High prevalence of hepatitis c virus (HCV) infection in some areas necessitates more investigations of the causative factors. Genetic factors that cause disruption in operation or secretion of interleukin 10 (IL-10), an anti inflammatory cytokine, may play a role in the intensity of the disease. The aim of this study was to evaluate genetic variants of IL-10 gene polymorphisms in HCV patients and their relationship with HCV disease. Fifty HCV patients and the same number of healthy individuals who were referred to hepatitis clinic in Mashhad, northeast of Iran, were recruited. Genomic DNA was extracted from whole blood. Genotyping for IL-10 gene promoter polymorphisms in three positions (-1082 G>A, 819 C>T and -592 C>A) was conducted by amplification refractory mutation system polymerase chain reaction. Haplotype analysis was performed using PHASE software. In a recessive analysis model of the -1082 position (GG vs. AA+AG), GG genotype was more common in patients (adjusted p = 0.02; OR = 4.66 [95% CI 1.31-16.35]). Also, ATA haplotype was more prevalent in HCV patients (adjusted p = 0.061; OR = 1.87 [95% CI 0.97-3.61]). Also, ATC/GCA diplotypes were more common in controls (adjusted p=0.002; adjusted OR = 0.27 [95% CI 0.11-0.63]). Although we found a possible association between IL-10 promoter polymorphisms and HCV infection, certain genotypes or diplotypes may confer a higher risk or susceptibility for developing HCV infection. PMID- 25119897 TI - Expression of GOLPH2 is associated with the progression of and poor prognosis in gastric cancer. AB - Golgi phosphoprotein 2 (GOLPH2) has been associated with the development and progression of various human cancers. The aims of this study were to investigate the relationship between GOLPH2 and gastric cancer (GC) progression and explore the clinical significance of GOLPH2 in GC. GOLPH2 expression was examined in four pairs of primary GC tissues and the adjacent non-cancerous tissues from the same patients, using immunohistochemistry (IHC), quantitative PCR and western blotting. Furthermore, GOLPH2 protein expression was analyzed in 10 normal gastric tissues and 385 clinicopathologically characterized cases of GC by IHC. Statistical analyses were performed to determine the prognostic and diagnostic associations. GOLPH2 mRNA and protein expression were both markedly upregulated in GC tissues, compared with the paired adjacent non-cancerous tissues. The Chi square test and Spearman analysis revealed a significant correlation between GOLPH2 expression and clinical stage, T classification, lymph node metastasis, metastasis and venous invasion. Patients with a higher GOLPH2 expression had a shorter overall survival (OS), compared to patients with lower GOLPH2 expression. Notably, our results suggested that GOLPH2 is associated with the development and progression of GC. Therefore, additional studies focusing on the potential of GOLPH2 as a novel therapeutic target in GC are required. PMID- 25119898 TI - Desmocollin-2 affects the adhesive strength and cytoskeletal arrangement in esophageal squamous cell carcinoma cells. AB - Desmocollin-2 (DSC2), a transmembrane glycoprotein belonging to the desmosomal cadherin family, has been found to be differentially expressed in several types of cancer and to be involved in tumor progression. The tumor metastasis suppressing property of DSC2 in esophageal squamous cell carcinoma (ESCC) has been described, however, its contribution to cell cohesion in ESCC remains to be elucidated. In the present study, using RNA interference (RNAi), the expression of DSC2 was silenced in SHEEC and KYSE510 cells. Hanging drop and fragmentation assays were performed to investigate the role of DSC2 in cell-cell adhesion. Western blot analysis and confocal microscopy were used to analyze the expression and localization of cell adhesion molecules and cytoskeletal arrangement. The results demonstrated that DSC2 knock down by RNAi caused defects in cell-cell adhesion and a concomitant reduction in desmosomal protein expression and adherens junction molecule distribution. A decrease in the expression of DSC2 caused an increase in free gamma-catenin levels, thus promoting its recruitment to the adherens junction complex. In addition, the RNAi-mediated inhibition of DSC2 led to keratin intermediate filament retraction and filamentous-actin cytoskeleton rearrangement. Taken together, these data support our previous findings and the proposal that DSC2 may be involved in the regulation of the invasive behavior of cells by a mechanism that controls cell-cell attachment and cytoskeleton rearrangement. PMID- 25119899 TI - Inferring the provenance of an alien species with DNA barcodes: the neotropical butterfly Dryas iulia in Thailand. AB - The Neotropical butterfly Dryas iulia has been collected from several locations in Thailand and Malaysia since 2007, and has been observed breeding in the wild, using introduced Passiflora foetida as a larval host plant. The butterfly is bred by a butterfly house in Phuket, Thailand, for release at weddings and Buddhist ceremonies, and we hypothesized that this butterfly house was the source of wild, Thai individuals. We compared wing patterns and COI barcodes from two, wild Thai populations with individuals obtained from this butterfly house. All Thai individuals resemble the subspecies D. iulia modesta, and barcodes from wild and captive Thai specimens were identical. This unique, Thai barcode was not found in any of the 30 specimens sampled from the wild in the species' native range, but is most similar to specimens from Costa Rica, where many exporting butterfly farms are located. These data implicate the butterfly house as the source of Thailand's wild D. iulia populations, which are currently so widespread that eradication efforts are unlikely to be successful. PMID- 25119901 TI - [Identification of three novel frameshift mutations in the RUNX2 gene in three sporadic Chinese cases with cleidocranial dysplasia]. AB - OBJECTIVE: To investigate the molecular etiology of three patients with sporadic cleidocranial dysplasia (CCD) and to provide genetic counseling and prenatal diagnosis for the family members based on the identified mutations. METHODS: Genomic DNA was extracted from peripheral blood samples using a standard method. All 7 coding exons of the RUNX2 gene and their flanking intronic sequences were amplified by PCR and sequenced directly. The PCR products of the exons with mutations from the three patients were cloned into a T-vector. Positive clones were sequenced. RESULTS: The three patients who have the typical CCD phenotypes involving clavicles, calvarium, stature, and teeth have carried various frameshift mutations in the RUNX2 gene. Patient 1 has a gross deletion of 80 nucleotides in exon 1 (c.227_306del), which caused a frameshift beginning at the Q/A repeat of the polypeptide and a premature termination (p.Ala76GlyfsX58). Patient 2 has a 2-bp duplication in exon 2 (c.471_472dupGG), which also caused a frameshift and a premature termination (p.Ala158GlyfsX19). Patient 3 has a T duplication in exon 7 (c.1321dupT), which caused a frameshift and a premature termination (p.Ser370PhefsX13) as well. CONCLUSION: The three novel mutations in RUNX2 are the underlying molecular mechanism for the CCD phenotypes of three sporadic Chinese patients, respectively. These have broadened the mutation spectrum of RUNX2 gene and provided a molecular basis for the genetic counseling and prenatal diagnosis for the affected families. PMID- 25119902 TI - [A novel mutation in GCH1 gene causes dopa-responsive dystonia]. AB - OBJECTIVE: To identify potential mutation of the GCH1 gene in a Chinese family affected with dopa-responsive dystonia. METHODS: Genomic DNA of patients was extracted from peripheral blood samples. The 6 exons of the GCH1 gene and at least 100 bp of flanking intronic sequences were amplified with PCR. Potential mutations were screened by direct sequencing. Identified mutation was verified with denaturing high performance liquid chromatography (DHPLC) in 100 healthy controls. RESULTS: All patients were found to be heterozygous for a novel c.597delT (p.Ala200LeufsX5) deletion in the exon 5 of the GCH1 gene. The deletion of T has resulted in formation of a shorter (203 amino acids) truncated non functional guanosine triphosphate cyclohydrolase I. The same mutation was not found in the 100 controls. CONCLUSION: A novel GCH1 gene frameshifing mutation probably underlies the dopa-responsive dystonia in this Chinese family. PMID- 25119903 TI - [Prenatal genetic diagnosis for two Chinese families affected with oculocutaneous albinism type II]. AB - OBJECTIVE: To perform genotyping analysis and subsequent prenatal genetic diagnosis for two families affected with oculocutaneous albinism (OCA). METHODS: Direct sequencing of TYR and P genes was performed in two albino probands. Family members were screened for corresponding mutant alleles. Prenatal genetic diagnoses were performed at early pregnancy by chorionic villus sampling (CVS) at mid-pregnancy through amniocentesis. RESULTS: No mutations were detected in the TYR gene in either probands, whereas 4 heterozygous mutations of the P gene were found, namely c.406C>T, c.535A>G, c.808-2A>G and c.2180T>C, among which c.535A>G and c.808-2A>G were novel. In the first round prenatal genetic testing, both fetuses were found to have the same genotypes as the probands. Both families had decided to terminate the pregnancy after genetic counseling. In the second round testing, neither of the fetuses was found to be affected by genotyping. The pregnancies continued and two healthy fetuses were born. CONCLUSION: OCA can be classified by genotyping, with which reliable prenatal diagnosis and feasible genetic counseling may be provided. PMID- 25119900 TI - SSU rDNA divergence in planktonic foraminifera: molecular taxonomy and biogeographic implications. AB - The use of planktonic foraminifera in paleoceanography requires taxonomic consistency and precise assessment of the species biogeography. Yet, ribosomal small subunit (SSUr) DNA analyses have revealed that most of the modern morpho species of planktonic foraminifera are composed of a complex of several distinct genetic types that may correspond to cryptic or pseudo-cryptic species. These genetic types are usually delimitated using partial sequences located at the 3'end of the SSUrDNA, but typically based on empirical delimitation. Here, we first use patristic genetic distances calculated within and among genetic types of the most common morpho-species to show that intra-type and inter-type genetic distances within morpho-species may significantly overlap, suggesting that genetic types have been sometimes inconsistently defined. We further apply two quantitative and independent methods, ABGD (Automatic Barcode Gap Detection) and GMYC (General Mixed Yule Coalescent) to a dataset of published and newly obtained partial SSU rDNA for a more objective assessment of the species status of these genetic types. Results of these complementary approaches are highly congruent and lead to a molecular taxonomy that ranks 49 genetic types of planktonic foraminifera as genuine (pseudo)cryptic species. Our results advocate for a standardized sequencing procedure allowing homogenous delimitations of (pseudo)cryptic species. On the ground of this revised taxonomic framework, we finally provide an integrative taxonomy synthesizing geographic, ecological and morphological differentiations that can occur among the genuine (pseudo)cryptic species. Due to molecular, environmental or morphological data scarcities, many aspects of our proposed integrative taxonomy are not yet fully resolved. On the other hand, our study opens up the potential for a correct interpretation of environmental sequence datasets. PMID- 25119904 TI - [Mutation analysis for a family affected with riboflavin responsive-multiple acyl CoA dehydrogenase deficiency]. AB - OBJECTIVE: To identify pathogenic mutation in a boy affected with riboflavin responsive-multiple acyl-CoA dehydrogenase deficiency (RR-MADD). METHODS: The patient was initially diagnosed as primary carnitine deficiency (PCD) and has been treated with carnitine supplementation for 7 years. Clinical manifestations and characteristics of fibula muscle specimen were analyzed. Potential mutation in electron transfer flavoprotein dehydrogenase (ETFDH) gene (for the patient and his parents) and carnitine transfer protein gene (SLC22A5) (for the patient) was screened. RESULTS: Electronic microscopy of the muscle specimen has suggested lipid storage myopathy. Mutation analysis has found that the patient carried compound heterozygous mutations, c.250G>A and c.380T>C, in exon 3 of the ETFDH gene, whilst his father and mother were heterozygous for the c.380T>C and c.250G>A mutations, respectively. Screening of the SLC22A5 gene has yielded no clinically meaningful result. After the establishment of diagnosis of RR-MADD, the condition of the patient has improved greatly with supplementation of high doses of riboflavin along with continuous carnitine supplement. CONCLUSION: The c.250G>A (p.Ala84Thr) mutation of exon 3 of the ETFDH gene has been a hot spot in Southern Chinese population, whilst the c.380T>C (p.Leu127Pro) is rarely reported. Our case has suggested that therapeutic diagnosis cannot substitute genetic testing. The mechanism for having stabilized the patient with only carnitine supplementation for 7 years needs further investigation. PMID- 25119905 TI - [Analysis of 22 patients with congenital cleft lip and palate using high resolution chromosome microarray]. AB - OBJECTIVE: To assess the value of chromosome microarray analysis (CMA) for identifying the etiology of patients with congenital cleft lip and palate. METHODS: Twenty-two patients with no identifiable chromosomal aberrations by conventional cytogenetic technique were selected. DNA was extracted and hybridized with Affymetrix CytoScan(TM) HD arrays following the manufacturer's protocol. The data were analyzed with a CHAS v2.0 software. RESULTS: CMA analysis has identified submicroscopic copy number variants (CNVs) in all of the cases, which have ranged from 100 kb to 1.8 Mb. Potential pathogenic CNVs were identified in 5 patients (22.7%), which involved microdeletions and microduplications on 8p23.1, 10q22.2-q22.3, 6q26, 20p12.1 and 18q12.3. MYST4, MACROD2 and SOX7 genes are likely the causative genes. CONCLUSION: CMA is an effective method for identification of etiology in patients with cleft lip and palate. CMA should be provided for patients with cleft lip and palate but a normal karyotype. Especially for those with additional structural abnormalities, there is a high risk for submicroscopic chromosomal aberrations. PMID- 25119906 TI - [Establishment and application of quantitative detection for heteroplasmic mtDNA mutation 3243A->G]. AB - OBJECTIVE: To develop a rapid, simple, cost-effective, accurate and sensitive method for quantitative detection of mitochondrial DNA (mtDNA) 3243A->G mutation in order to provide reference for selecting the best detection method under different conditions. METHODS: Genomic DNA was extracted from peripheral leucocytes of 17 individuals from a Wenzhou family featuring maternally inherited diabetes and deafness (MIDD). Heteroplasmic level of mtDNA 3243A->G mutation was determined respectively with polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP), real time-amplification refractory mutation system-quantitative PCR (RT-ARMS-qPCR) and pyrosquencing. Eleven plasmids with various heteroplasmic levels of the 3243A->G mutation (ranging from 0 to 100%)were constructed as the standards. The reliability of above methods was compared by correlation coefficient based on observed and expected values. RESULTS: For all three methods, measurement of the standards showed a linear correlation between the expected and detected values, i.e., PCR-RFLP (R(2)=0.828), RT-ARMS-qPCR (R(2)=0.998) and pyrosquencing (R(2)=0.997). For the MIDD family, it was consistent that there are 13 members carrying the A3243G mutation with different heteroplasmic levels. And there was no significant difference between the results by RT-ARMS-qPCR and pyrosquencing. CONCLUSION: PCR RFLP is not appropriate for the quantitative detection but could be used for early clinical screening. Both RT-ARMS-qPCR and pyrosquencing are suitable for the detection of low heteroplasmic level of A3243G mutation. Compared with pyrosquencing, RT-ARMS-qPCR is rapid, reliable and cost-effective, and is the best choice for detecting low mutation loads. PMID- 25119907 TI - [Genetic diagnosis and analysis of related genes for a pedigree with 2p25 and 12p13 cryptic rearrangements]. AB - OBJECTIVE: To analyze chromosome aberration in a child with mental retardation and abnormalities and its parents. METHODS: Chromosome G banding, multiplex ligation-dependent probe amplification, fluorescence in situ hybridization and single nucleotide polymorphisms array were employed for analysis. RESULTS: Karyotype analysis revealed that the child was 46,XX and the father was 46,XY, while the mother was 46,XX, add (12)(p13). Subtelomeric region analysis with MLPA displayed that the child has reduced ACP1 gene copy number in 2p25 region and increased SLC6A12,KDM5A gene copy numbers in 12p11 region. SNP-array has fine mapped the duplication to 12p13.33-p12.3, a 15.142 Mb region, and a deletion to 2p25.3 for 3.194 Mb, which resulted in duplication of 9 genes including SLC6A12 as well as deletion of 11 genes including SNTG2, respectively. FISH analysis revealed that the child was 46,XX,ish,der(2),t(2;12)(p25;p13)mat, or partial monosomy 2p25 and partial trisomy 12p13. In addition,the mother was a carrier with cryptic balanced translocation chromosome, 46,XX,isht(2;12) (p25;p13). Mental abnormalities and retardation of the child may be attributed to heterozygous deletion of SNTG2, MYT1L genes and duplication of SLC6A12 gene. CONCLUSION: Combined use of MLPA, FISH and SNP-array can facilitate accurate diagnosis of cryptic rearrangement at genomic level. PMID- 25119908 TI - [Association of CMA1 gene tag single nucleotide polymorphisms with essential hypertension in Yi population from Yunnan]. AB - OBJECTIVE: To assess the association of tag single nucleotide polymorphisms (tag SNPs) of chymase gene (CMA1) with essential hypertension in Yi population from Yunnan, China. METHODS: A case-control study was carried out. Four tag SNPs(rs1956921, rs1800876, rs5244 and rs1885108) were genotyped in 303 patients with essential hypertension and 312 healthy controls using polymerase chain reaction - restriction fragment length polymorphism(PCR-RFLP) method. RESULTS: No significant difference in genotypic and allelic distributions of the four polymorphisms was detected between the two groups(P>0.05), and the same results existed in the females. The frequencies of rs1956921 C allele and a C-T haplotype constructed with rs1956921 and rs5244 were greater in male patients compared with male controls(P<0.01). CONCLUSION: The rs1956921 C allele of the CMA1 gene and the C-T haplotype constructed with rs1956921 and rs5244 may be risk factors for essential hypertension in ethnic Yi males from Yunnan. PMID- 25119909 TI - [Association of TLR4 gene polymorphisms with large artery atherosclerotic stroke and vascular bed selectivity of atherosclerotic lesions]. AB - OBJECTIVE: To assess the association of TLR4 gene polymorphisms with large artery atherosclerosis (LAA) stroke and liability to atherosclerosis in an ethnic Han population from northern China. METHODS: The study has involved 286 LAA stroke patients and 300 healthy controls. The LAA group has been divided 4 subsets according to angiostenosis conditions. Polymerase chain reaction-restriction fragment length polymorphism and pyrosequencing were employed to analyze three single nucleotide polymorphism (SNPs) (rs1927914, rs1927911 and rs2149356) of the TLR4 gene. A Haploview software package was used to analyze the haplotypes. RESULTS: SNPs rs1927911 and rs2149356 were associated with LAA stroke. Genotypic and allelic frequencies of rs1927914 did not differ significantly between the two groups. Genetic variants of the three SNPs did not vary significantly between all subsets. Haplotype analysis was revealed a significant difference between the LAA group and the control group. Compared with the controls, the frequencies of haplotypes H2 and H8 were lower, and that of H3 was greater in the LAA group. CONCLUSION: An association between the TLR4 gene polymorphisms and LAA stroke subtype in ethnic Han population in northern China has been found. However, no association of liability to atherosclerosis in different vascular bed has been found with these polymorphisms. PMID- 25119910 TI - [Influence of assisted reproduction technologies on genomic imprinting of embryos and offspring]. AB - Assisted reproduction technologies (ART) include controlled ovarian hyperstimulation, in vitro fertilization-embryo transfer, intracytoplasmic sperm injection, in vitro maturation of oocytes, pre-implantation genetic diagnosis, etc. They have been used for the treatment of impaired fertility but may damage the health of offspring. The ART procedures may alter the epigenetic status of these offspring and DNA methylation may be a crucial mechanism. This paper summarizes epigenetic alterations in ART embryos and offspring, and discusses the risks. PMID- 25119911 TI - [The function of transcription factor P63 and its signaling pathway during limb development]. AB - The development of human limb is controlled by several transcription factors and signaling pathways, which are organized in precise time- and space-restricted manners. Recent studies showed that P63 and its signaling pathway play important roles in this process. Transcription factor P63, one member of the P53 family, is characterized by a similar amino acid domain, plays a crucial role in the development of limb and ectoderm differentiation, especially with its DNA binding domain, and sterile alpha motif domains. Mutated P63 gene may produce abnormal transcription factor P63 which can affect the signaling pathway. Furthermore, defective signaling protein in structure and/or quantity is synthesized though the pathway. Eventually, members of the signaling protein family are involved in the regulation of differentiation and development of stem cell, which causes deformity of limbs. In brief, three signaling pathways are related to the digit formation along three axes, including SHH-ZPA, FGFs-AER and Lmx1B-Wnt7a-En1. Each contains numerous signaling molecules which are integrated in self-regulatory modules that assure the acquisition or the correct digit complements. These finding has brought new clues for deciphering the etiology of congenital limb malformation and may provide alternatives for both prevention and treatment. PMID- 25119912 TI - [Detection of mosaic trisomy 9 missed by conventional cytogenetics using SNP array and fluorescence in situ hybridization]. AB - OBJECTIVE: To detect mosaic trisomy 9 missed by conventional cytogenetics. METHODS: Peripheral blood genomic DNA from a girl with mental retardation was analyzed using Affymetrix CytoScan (TM) HD array. Fluorescence in situ hybridization (FISH) was also performed on samples from two patients. RESULTS: The SNP-array analysis has revealed multiple duplications along chromosome 9. FISH analysis showed that, for the peripheral blood sample from one patient, 40 of 100 interphase cells and 15 of 100 metaphase cells carried trisomy 9. For the cord blood sample from another patient, 35 of 100 interphase cells and 10 of 100 cultured cells carried trisomy 9. CONCLUSION: SNP-array is useful for detecting low-level mosaicism which may be missed by conventional cytogenetics. Combined with karyotype and microarray analyses, FISH is a focused and targeted approach for diagnosing mosaic trisomy. They may provide a useful tool for differentiating pseudomosaicisms from true mosaicisms. PMID- 25119913 TI - [Identification of a novel splicing mutation in COL1A1 gene in a Chinese family affected with typeIosteogenesis imperfecta]. AB - OBJECTIVE: To investigate the genetic cause for a large family affected with typeIosteogenesis imperfecta. METHODS: Genomic DNA was extracted from peripheral venous blood samples. The entire coding region and intron-exon boundaries of the COL1A1 gene were subjected to PCR amplification and direct sequencing. Total RNA was also extracted from immortalized B cell lines from the patients, with the first strand of cDNA synthesized with an oligo(dT)18 primer. The PCR products were directly sequenced using the TA cloned plasmid. RESULTS: A c.3208G>A mutation has been identified in the COL1A1 gene, which can alter the splicing pattern of mRNA. CONCLUSION: A novel splicing mutation c.3208G>A of the COL1A1 gene probably underlies the disease. PMID- 25119915 TI - [Establishment of an allele-specific PCR method for direct screening of CYP21A2 gene mutation]. AB - OBJECTIVE: To establish an allele-specific PCR method for detect screening of CYP21A2 gene mutation. METHODS: Allele-specific PCR primers and analogy primers were designed based on the sequence alignment of CYP21A2 and CYP21AP genes. Genomic DNA was extracted from blood specimens of 4 patients with 21-hydroxylase deficiency and 5 healthy controls and respectively amplified with allele-specific PCR primers and analogy primers and sequenced. RESULTS: Mutations of CYP21A2 including IVS2-13A/C>G, Arg356Trp and Arg149Pro were found with the established method in all of the 4 patients but not in the healthy controls. When detected with the analogy primers set, IVS2-13A/C>G and Arg356Trp were observed in both patients and healthy controls. CONCLUSION: The allele-specific PCR-based method is a simple, effective and reliable method for the detection of CYP21A2 gene mutation. PMID- 25119914 TI - [Limb-girdle muscular dystrophy type 2G: clinical, pathological and genetic analysis of a case]. AB - OBJECTIVE: To investigate TCAP gene mutation and clinical features of a Chinese patient with limb-girdle muscular dystrophy type 2G(LGMD 2G). METHODS: Clinical data of the patient was analyzed. Exons of the TCAP gene were amplified and sequenced. RESULTS: The patient has presented clinically as LGMD and pathologically as vacuolar myopathy. Genetic analysis has identified compound heterozygous mutations of exons 1 and 2 of the TCAP gene(c.100delC, c.166insG). CONCLUSION: LGMD is a group of neuromuscular disorders with substantial phenotypic heterogeneity. Genetic diagnosis has become indispensable for accurate diagnosis for patients suspected to have the disease. PMID- 25119916 TI - [Result survey analysis of prenatal chromosome karyotyping in an external quality assessment program]. AB - OBJECTIVE: To analyze the results of prenatal karyotype of the external quality assessment program in 2013 in order to provide references and recommendations for improving the capability and performances of karyotype analysis of prenatal screening laboratories. METHODS: Five lots of quality control cell photos were sent to 500 laboratories. The participants were asked to decide whether the photos have demonstrated any abnormal karyotype and determine the abnormal type. The results should be submitted before the deadline and compared with the standard results to evaluate the performances of the laboratory. RESULTS: One hundred forty three laboratories have returned their karyotype results for the survey. The standard answers were 7,XX,+18, 46,X,i(X)(q10), 46,XY,i(21)(q10) or 46,XY,+21,der(21;21)(q10;q10), 46,XY and 47,XY,+21 in sequential order, which were used to estimate the score of each participant. The pass rates for five lots were 97.9%, 97.2%, 95.8%, 100.0% and 97.9%, respectively. The total pass rate was 97.7%. The error rates were 2.1%, 2.8%, 4.2%, 0 and 2.1%, respectively. The total error rate was 2.3%. CONCLUSION: Some laboratories did not correctly identify the abnormal karyotypes, while some could not determine the right type of karyotype. The external quality assessment program of prenatal diagnosis of karyotype analysis should be conducted annually in order to improve the capability and performances of karyotype analysis of prenatal screening laboratories. PMID- 25119917 TI - [Analysis of erythroid-specific blood group genes using un-mobilized peripheral stem cells cultured in vitro]. AB - OBJECTIVE: To analyze specific expression of blood group genes using nucleated erythroid cells cultured from un-mobilized peripheral stem cells in vitro. METHODS: Hematopoietic stem cells(HSC) bearing the CD34 antigen were isolated from peripheral blood by centrifugation and magnetic beads sorting, followed by suspension culture in vitro. Cells were collected from medium on various stages and analyzed by immunofluorescence. The RNA transcription of RH and ABO blood group genes was analyzed using culture cells on day 12. RESULTS: A total of(3.19+/-0.13) *10 (4) CD34+cells were isolated from about 50 mL peripheral blood with a recovery rate of 67.3%+/-2.7%. The cells amount in erythroid-lineage culture system on day 9 reached a plateau of a 237.1+/-15.5-fold amplification of the initial cell input. The stem cell-specific CD34 antigen was dropped off, while the erythroid-specific CD235a and CD240D antigens were increased in culture period. RHD/CE and ABO genes can be amplified using RNA extracted from culture cells on day 12, and genotypes of Rh and ABO systems by DNA sequencing were consistent with their serologic phenotypes. CONCLUSION: A method was established to analyze the gene expression of erythroid blood group derived from un-mobilized peripheral stem cells cultured in vitro. It can be used to study the expression of various erythroid-specific genes. PMID- 25119918 TI - [Association of MMP-14 gene polymorphism with cerebral infarction - a case control study]. AB - OBJECTIVE: To investigate the association between cerebral infarction (CI) and single nucleotide polymorphism (SNP) in the exon of membrane-type 1 matrix metalloproteinase (MMP-14) gene in Chinese Han population. METHODS: Five hundred seventy four patients with CI and 463 healthy individuals were recruited. Serum MMP-14 level was measured with enzyme-linked immunosorbent assay (ELISA). rs1042704 and rs2236307 polymorphisms of the MMP-14 gene were genotyped with a TaqMan assay. Multivariate logistic regression was carried out to analyze the risk factors of CI. RESULTS: A significant lower risk of CI was found in individuals with MMP-14 rs2236307 TC and CC genotypes (vs. TT genotype: P<0.05). The frequencies of MMP-14 rs2236307 C allele were significantly different between the CI group (37.46%) and the control group (43.95%) (P=0.003). Serum level of MMP-14 was higher in the CI group (P=0.003) and was also higher in the group with MMP-14 rs2236307 TT genotype compared with those with CT and CC genotypes (P=0.000; P=0.009). Logistic regression analysis indicated that the MMP-14 rs2236307 CT+CC genotypes was a protective factor, and that history of hypertension, smoking status, triglycerides, diastolic blood pressure and systolic blood pressure were the independent risk factors of CI (AOR:2.027, 1.302, 1.296, 1.434, 2.087; P<0.05). CONCLUSION: The rs2236307 polymorphism of MMP-14 gene is associated with CI, for which the C allele maybe a protective factor. No association of MMP-14 gene rs1042704 polymorphism with CI has been found. PMID- 25119919 TI - [Analysis for 2 samples with HLA-DQB1 allele dropout at exon 2 in sequence-based typing]. AB - OBJECTIVE: To explore the reason for HLA-DQB1 allele dropout during routine sequence-based typing(SBT) in order to improve the accuracy of typing. METHODS: Two thousand samples derived from HLA high-resolution typing laboratory were typed for HLA-DQB1 locus using an AlleleSEQR HLA-DQB1 SBT kit. Non-conclusive results and "abnormal" sequencing samples were retyped using a LABType rSSO HD HLA-DQB1 kit and further analyzed with both sequence-specific primers and group specific primers and sequenced for haplotype analysis. RESULTS: Among the 2000 samples, 2 samples with no conclusive result were identified. The heterozygosity was confirmed with both the LAB Type SSO HD HLA-DQB1 kit and PCR-SBT in house method. Subsequent HLA-DQB1 cloning and haplotype sequencing have elucidated that HLA-DQB1*02:02 dropped out at exon 2 for the first sample and HLA-DQB1*02:01:01 dropped out at exon 2 for the second sample during PCR amplification. No novel nucleotide mutation was found. CONCLUSION: Our results indicated that preferential amplification at exon 2 of DQB1 may result in allele dropout in exon 2 sequences during HLA-DQB1 SBT test. This may provide useful information for HLA genotyping. PMID- 25119921 TI - [Spinocerebellar ataxia-a family with eight cases]. PMID- 25119920 TI - [Detection of p53 gene deletion in Xinjiang patients with chronic lymphocytic leukemia by fluorescence in situ hybridization and its clinical significance]. AB - OBJECTIVE: To investigate the presence of p53 gene deletion in Xinjiang patients with chronic lymphocytic leukemia and its clinical significance. METHODS: Interphase fluorescence in situ hybridization (FISH) was used to detect the p53 gene deletion in 77 patients with CLL. Presence of the deletion and its association with clinical and laboratory features as well as prognostic factors were analyzed. Kaplan-Meier method was used to calculate survivals, and the results were compared using a Log-rank test. RESULTS: p53 gene deletion was found in 10 (12.9%) of the patients but none from the control group (P<0.05). The deletion was found in 12.5% (4/32) of ethnic Hans and 13.3% (6/45) of ethnic Uyghurs (P>0.05). No significant different distribution of p53 gene deletion was found in regard to sex, age, ethnicity, peripheral blood cell count (except for Hb) or the levels of lactate dehydrogenase, beta2-micro globulin and CD38 (P>0.05). The deletion rate was higher in the group with high expression of ZAP 70 and patients with advanced stage disease than that in the group of low expression and early-stage CLL (P<0.05). Among 20 patients who received fludarabine therapy, the overall remission rate for those with p53 gene deletion (20%) was lower than those without (75%) (P<0.05). With a median follow-up time of 39.0 (8.0-136.0) months, 11 cases had died (14.3%), among them, 7 cases died from CLL and related complications, and all of them were founded p53 gene deletion. In patients with p53 gene deletion, the progression-free survival (18 months) was shorter than those without the deletion (55 months) (P<0.05). CONCLUSION: The p53 gene deletion has been found in more than 10% of patients with CLL, and the deletion rate did not significantly differ between ethnic Han and Uyghur patients. The deletion is associated with advanced stage of the disease. High-level ZAP-70 expression and the presence of p53 deletion are associated with shorter survival and poor response to fludarabine containing therapy. Therefore, drugs affecting the p53 signaling pathway should be avoided. PMID- 25119922 TI - [Association of polymorphisms of HLA-DRB1 gene with unexplained recurrent spontaneous abortion in ethnic Hans from Henan]. AB - OBJECTIVE: To assess the association of polymorphisms of human leukocyte antigen DRB1 gene (HLA-DRB1) with susceptibility to unexplained recurrent spontaneous abortion (URSA). METHODS: The HLA-DRB1 gene was typed with polymerase chain reaction-specific sequence primers (PCR-SSP) method in 200 couples with URSA and 200 couples with a normal pregnancy history. RESULTS: The frequencies of DRB1*09 and DRB1*13 alleles were significantly greater in the URSA group compared with the control group (14.50% vs. 9.50%, and 7.00% vs. 4.38%, both P<0.05), whilst the frequencies of DRB1*04 and DRB1*12 alleles were significantly lower (7.13% vs. 10.75%, and 8.63% vs. 14.38%, both P<0.05). For females from the URSA group, the frequency of DRB1*09 allele (14.00%) was significantly higher compared with the controls (9.25%) (P=0.036), whilst the frequency of DRB1*12(8.50%) allele was significantly lower (14.00%) (P=0.014). For males in the URSA group, the frequencies of DRB1*09 and DRB1*13 alleles were significantly higher than those of the controls (15.00% vs. 9.75%, and 9.25% vs. 4.00%, both P<0.05), whilst the frequencies of DRB1*04 and DRB1*12 alleles were significantly lower (5.75% vs. 12.25%, and 8.75% vs. 14.75%, P<0.05). CONCLUSION: The DRB1*09 and DRB1*13 alleles may contribute to the susceptibility of URSA, while DRB1*04 and DRB1*12 alleles may confer a protective effect factors. For females, however, no significant association of DRB1*13 and DRB1*04 alleles with URSA was found. PMID- 25119923 TI - [Clinical and genetics characteristics of patients with monosomal karyotype acute myeloid leukemia patients]. AB - OBJECTIVE: To investigate the clinical and genetics characteristics of patients with monosomal karyotype acute myeloid leukemia (MK-AML). METHODS: The karyotypes of 3743 patients with newly-diagnosed de novo AML were analyzed, which had identified 153 cases with MK-AML, for whom the clinical and genetics characteristics were analyzed. RESULTS: There were 2056 patients (54.9%) among all patients. A total of 153 patients fulfilling the criteria for MK-AML were identified, which comprised 93 males and 60 females, with a median age of 54. The median white blood cell count on presentation was 4.4*10 (9)/L. One hundred and forty-five cases (94.8%) have fulfilled the criteria for complex karyotype (>= 3 chromosomal abnormalities). Although the monosomy could be found with all autosomes, chromosome 7 has been most frequently involved (38.56%, 59/153). CONCLUSION: MK-AML is a distinct cytogenetic subtype of AML. Monosomy 7 is frequently detected among MK-AML patients. The monosomal karyotype is common among elder patients with AML. PMID- 25119924 TI - [Sequence analysis of a novel allele HLA-C*01:78]. AB - OBJECTIVE: To investigate the genetic basis for a novel allele HLA-C*01:78. METHODS: Genomic DNA was extracted from peripheral blood using a QIAGEN quick DNA extraction kit. The regions encompassing HLA-C from exon 1 to intron 3 and intron 3 to 3'UTR were amplified and cloned using a cloning sequencing kit in order to split the two alleles apart. Selected clones were sequenced to include exons 2 to 4. RESULTS: Sequencing results have indicated the HLA-C alleles of the proband to be a novel C*03:04 allele. The sequence has been submitted to GenBank (KF049216). BLAST analysis has confirmed the novel allele to have one nucleotide difference as C*01:03 at genomic nt316C>A (codon 82CGC>AGC) in exon 2, which has resulted in replacement of one amino acid (82R>S). CONCLUSION: The novel allele has been officially named as C*01:78 by the WHO Nomenclature Committee. The HLA allele type of the proband was therefore A*02:07, 24:02; B*40:01, 46:01; C*01:78, 03:04; DQB1*05:02, 05:02; DRB1*16:02, 16:02. PMID- 25119925 TI - [Identification of a novel allele HLA-B*37:04:02]. AB - OBJECTIVE: To report on a novel HLA allele identified in a Chinese individual. METHODS: Routine HLA genotyping was carried out with polymerase chain reaction sequence specific oligonucleotide probes (PCR-SSOP) and sequencing-based typing (SBT). RESULTS: A new HLA allele has been identified. The sequence differed from its closest allele B*37:04:01 at nt618 (GCG->GCA), which resulted in no change of codon 206. CONCLUSION: A novel HLA allele HLA-B*37:04:02 (GU391034) has been identified and officially named by the WHO Nomenclature Committee. PMID- 25119927 TI - [Two pedigrees with benign adult familial myoclonic epilepsy]. PMID- 25119926 TI - [Confirmation of 17 rare HLA alleles and prediction of their haplotypes]. AB - OBJECTIVE: To confirm 17 rare HLA alleles detected during routine HLA typing and deduce their haplotypes. METHODS: Bi-allelic sequence-based typing and Luminex DNA PCR-SSOP assay were applied for the initial or repeat HLA typing, respectively. The rare HLA alleles were confirmed with mono-allelic sequence based typing. Predicted haplotypes of the rare alleles were inferred based on the frequencies of HLA alleles and haplotypes in Han population. RESULTS: The authenticity of the total 17 rare HLA alleles was proven, and 18 predicted haplotypes associated with the rare alleles were recognized. A*11:12 and DRB1*13:19 were detected twice among unrelated individuals. CONCLUSION: Study of rare HLA alleles and predicted haplotype can provide useful information for donor searching and transplantation, and enrich polymorphisms of HLA in this population. PMID- 25119928 TI - [Hereditary spinocerebellar ataxia-a pedigree with six cases]. PMID- 25119931 TI - Excited-state wavepacket and potential reconstruction by coherent anti-Stokes Raman scattering. AB - Among the major challenges in the chemical sciences is controlling chemical reactions and deciphering their mechanisms. Since much of chemistry occurs in excited electronic states, in the last three decades scientists have employed a wide variety of experimental techniques and theoretical methods to recover excited-state potential energy surfaces and the wavepackets that evolve on them. These methods have been partially successful but generally do not provide a complete reconstruction of either the excited state wavepacket or potential. We have recently proposed a methodology for reconstructing excited-state molecular wavepackets and the corresponding potential energy surface [Avisar and Tannor, Phys. Rev. Lett., 2011, 106, 170405]. In our approach, the wavepacket is represented as a superposition of the set of vibrational eigenfunctions of the molecular ground-state Hamiltonian. We assume that the multidimensional ground state potential surface is known, and therefore these vibrational eigenfunctions are known as well. The time-dependent coefficients of the basis functions are obtained by experimental measurement of the resonant coherent anti-Stokes Raman scattering (CARS) signal. Our reconstruction strategy has several significant advantages: (1) the methodology requires no a priori knowledge of any excited state potential. (2) It applies to dissociative as well as to bound excited-state potentials. (3) It is general for polyatomics. (4) The excited-state potential surface is reconstructed simultaneously with the wavepacket. Apart from making a general contribution to the field of excited-state spectroscopy, our method provides the information on the excited-state wavepacket and potential necessary to design laser pulse sequences to control photochemical reactions. PMID- 25119929 TI - Novel secondary somatic mutations in Ewing's sarcoma and desmoplastic small round cell tumors. AB - BACKGROUND: Ewing's sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT. METHODOLOGY: Twenty eight patients with ES or DSRCT had tumor tissue available that could be analyzed by one of the following methods: 1) Next-generation exome sequencing platform; 2) Multiplex PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene mutation screening; 4) Sanger sequencing; 5) Morphoproteomics. PRINCIPAL FINDINGS: Novel somatic mutations were identified in four out of 18 patients with advanced ES and two of 10 patients with advanced DSRCT (six out of 28 (21.4%));KRAS (n = 1), PTPRD (n = 1), GRB10 (n = 2), MET (n = 2) and PIK3CA (n = 1). One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation achieved a complete remission (CR) on an Insulin like growth factor 1 receptor (IGF1R) inhibitor based treatment. One patient, who achieved a partial remission (PR) with IGF1R inhibitor treatment, but later developed resistance, demonstrated a KRAS mutation in the post-treatment resistant tumor, but not in the pre treatment tumor suggesting that the RAF/RAS/MEK pathway was activated with progression. CONCLUSIONS: We have reported several different mutations in advanced ES and DSRCT that have direct implications for molecularly-directed targeted therapy. Our technology agnostic approach provides an initial mutational roadmap used in the path towards individualized combination therapy. PMID- 25119930 TI - Final results of a phase II study of paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. AB - BACKGROUND: Efficacy and safety data for combining bevacizumab, gemcitabine, and paclitaxel for locally advanced/metastatic breast cancer are limited. PATIENTS AND METHODS: AVALUZ trial evaluates the combination of bevacizumab 10 mg/kg, gemcitabine 2,000 mg/m(2) plus paclitaxel 150 mg/m(2), on days 1 and 15 of each 28-day course in previously untreated HER-2 negative patients. RESULTS: Median progression-free survival (PES): 12.3 months. The overall response and clinical benefit rate (CR + PR + SD) were 72 % (95 % CI 60.9-82.0 %) and 89 % (95 % CI 80.3-95.3 %), respectively. Median overall survival: 27.4 mo. Baseline circulating tumor cell (CTCs) >=2 versus CTCs <2 was associated with lower PFS, p = 0.046. Overall response was significantly greater in patients with intense angiotensin type 1 receptor (AGTR1) expression (99 vs. 60 % [p = 0.021]). The most frequent grade 3/4 adverse events were: neutropenia (10 %); febrile neutropenia (1 %); sensory neuropathy (13 %); and asthenia (6 %). Grade 3 adverse events of interest with bevacizumab included bleeding (1 %) and hypertension (4 %). One patient developed cardiac ischemia (1 %). CONCLUSIONS: Adding bevacizumab to chemotherapy appeared feasible and well tolerated, producing toxicity comparable to other effective combined first-line regimens. Baseline circulating endothelial cells and AGTR1 expression are predictive of PFS and response. PMID- 25119932 TI - Screening for depressive symptoms in older adults in the Family Health Strategy, Porto Alegre, Brazil. AB - OBJECTIVE To analyze the prevalence of depression in older adults and associated factors. METHODS Cross-sectional study using a stratified random sample of 621 individuals aged >= 60 from 27 family health teams in Porto Alegre, RS, Southern Brazil, between 2010 and 2012. Community health agents measured depression using the 15-item Geriatric Depression Scale. Scores of >= 6 were considered as depression and between 11 and 15 as severe depression. Poisson regression was used to search for independent associations of sociodemographic and self perceived health with both depression and its severity. RESULTS The prevalence of depression was 30.6% and was significantly higher in women (35.9% women versus 20.9% men, p < 0.001). The variables independently associated with depression were: female gender (PR = 1.4, 95%CI 1.1;1.8); low education, especially illiteracy (PR = 1.8, 95%CI 1.2;2 6); regular self-rated health (OR = 2.2, 95%CI 1.6;3.0); and poor/very poor self-rated health (PR = 4.0, 95%CI 2.9;5.5). Except for education, the strength of association of these factors increases significantly in severe depression. CONCLUSIONS A high prevalence of depression was observed in the evaluations conducted by community health agents, professionals who are not highly specialized. The findings identified using the 15-item Geriatric Depression Scale in this way are similar to those in the literature, with depression more associated with low education, female gender and worse self-rated health. From a primary health care strategic point of view, the findings become still more relevant, indicating that community health agents could play an important role in identifying depression in older adults. PMID- 25119933 TI - Disability in instrumental activities of daily living among older adults: gender differences. AB - OBJECTIVE To analyze gender differences in the incidence and determinants of disability regarding instrumental activities of daily living among older adults. METHODS The data were extracted from the Saude, Bem-Estar e Envelhecimento (SABE Health, Wellbeing and Ageing) study. In 2000, 1,034 older adults without difficulty in regarding instrumental activities of daily living were selected. The following characteristics were evaluated at the baseline: sociodemographic and behavioral variables, health status, falls, fractures, hospitalizations, depressive symptoms, cognition, strength, mobility, balance and perception of vision and hearing. Instrumental activities of daily living such as shopping and managing own money and medication, using transportation and using the telephone were reassessed in 2006, with incident cases of disability considered as the outcome. RESULTS The incidence density of disability in instrumental activities of daily living was 44.7/1,000 person/years for women and 25.2/1,000 person/years for men. The incidence rate ratio between women and men was 1.77 (95%CI 1.75;1.80). After controlling for socioeconomic status and clinical conditions, the incidence rate ratio was 1.81 (95%CI 1.77;1.84), demonstrating that women with chronic disease and greater social vulnerability have a greater incidence density of disability in instrumental activities of daily living. The following were determinants of the incidence of disability: age >= 80 and worse perception of hearing in both genders; stroke in men; and being aged 70 to 79 in women. Better cognitive performance was a protective factor in both genders and better balance was a protective factor in women. CONCLUSIONS The higher incidence density of disability in older women remained even after controlling for adverse social and clinical conditions. In addition to age, poorer cognitive performance and conditions that adversely affect communication disable both genders. Acute events, such as a stroke, disables elderly men more, whereas early deficits regarding balance disable women more. PMID- 25119934 TI - Cut-off point for WHOQOL-bref as a measure of quality of life of older adults. AB - OBJECTIVE To propose a cut-off for the World Health Organization Quality of Life Bref (WHOQOL-bref) as a predictor of quality of life in older adults.METHODS Cross-sectional study with 391 older adults registered in the Northwest Health District in Belo Horizonte, MG, Southeastern Brazil, between October 8, 2010 and May 23, 2011. The older adults' quality of life was measured using the WHOQOL bref. The analysis was rationalized by outlining two extreme and simultaneous groups according to perceived quality of life and satisfaction with health (quality of life good/satisfactory - good or very good self-reported quality of life and being satisfied or very satisfied with health - G5; and poor/very poor quality of life - poor or very poor self-reported quality of life and feeling dissatisfied or very dissatisfied with health - G6). A Receiver-Operating Characteristic curve (ROC) was created to assess the diagnostic ability of different cut-off points of the WHOQOL-bref.RESULTS ROC curve analysis indicated a critical value 60 as the optimal cut-off point for assessing perceived quality of life and satisfaction with health. The area under the curve was 0.758, with a sensitivity of 76.8% and specificity of 63.8% for a cut-off of >= 60 for overall quality of life (G5) and sensitivity 95.0% and specificity of 54.4% for a cut-off of < 60 for overall quality of life (G6).CONCLUSIONS Diagnostic interpretation of the ROC curve revealed that cut-off < 60 for overall quality of life obtained excellent sensitivity and negative predictive value for tracking older adults with probable worse quality of life and dissatisfied with health. PMID- 25119935 TI - Social protection systems in vulnerable families: their importance for the public health. AB - OBJECTIVE To analyze the effectiveness of the Chilean System of Childhood Welfare in transferring benefits to socially vulnerable families. METHODS A cross sectional study with a sample of 132 families from the Metropolitan Region, Chile, stratified according to degree of social vulnerability, between September 2011 and January 2012. Semi-structured interviews were conducted with mothers of the studied families in public health facilities or their households. The variables studied were family structure, psychosocial risk in the family context and integrated benefits from the welfare system in families that fulfill the necessary requirements for transfer of benefits. Descriptive statistics to measure location and dispersion were calculated. A binary logistic regression, which accounts for the sample size of the study, was carried out. RESULTS The groups were homogenous regarding family size, the presence of biological father in the household, the number of relatives living in the same dwelling, income generation capacity and the rate of dependency and psychosocial risk (p >= 0.05). The transfer of benefits was low in all three groups of the sample (<= 23.0%). The benefit with the best coverage in the system was the Single Family Subsidy, whose transfer was associated with the size of the family, the presence of relatives in the dwelling, the absence of the father in the household, a high rate of dependency and a high income generation capacity (p <= 0.10). CONCLUSIONS The effectiveness of benefit transfer was poor, especially in families that were extremely socially vulnerable. Further explanatory studies of benefit transfers to the vulnerable population, of differing intensity and duration, are required in order to reduce health disparities and inequalities. PMID- 25119936 TI - Perceived health in the Portuguese population aged >= 35. AB - OBJECTIVE: To evaluate the exploratory relationship between determinants of health, life satisfaction, locus of control, attitudes and behaviors and health related quality of life in an adult population. METHODS: Observational study (analytical and cross-sectional) with a quantitative methodological basis. The sample was composed oy 1,214 inhabitants aged >= 35 in 31 civil parishes in the County of Coimbra, Portugal, 2011-2012. An anonymous and voluntary health survey was conducted, which collected the following information: demographic, clinical record, health and lifestyle behaviors; health related quality of life (Medical Outcomes Study, Short Form-36); health locus of control; survey of health attitudes and behavior, and quality of life index. Pearson's Linear Correlation, t-Student, Wilcoxon-Mann-Whitney; One-way ANOVA; Brown-Forsythe's F; Kruskal Wallis; Multiple Comparisons: Tukey (HSD), Games-Howell and Conover were used in the statistical analysis. RESULTS: Health related quality of life was shown to be lower in females, in older age groups, in obese/overweight individuals, widows, unassisted, those living alone, living in rural/suburban areas, those who did not work and with a medium-low socioeconomic level. Respondents with poor/very poor self-perceived health (p < 0.0001), with chronic disease (p < 0.0001), who consumed < 3 meals per day (p <= 0.01), who were sedentary, who slept <= 6 h/day and had smoked for several years revealed the worst health results. Health related quality of life was positively related with a bigger internal locus, with better health attitudes and behaviors (physical exercise, health and nutritional care, length of dependence) and with different areas of life satisfaction. CONCLUSIONS: Better health related quality of life was associated with certain social, psychological, family and health characteristics, a satisfactory lifestyle, better socioeconomic conditions and a good internal locus of control over health attitudes and behaviors. PMID- 25119937 TI - HIV risk practices by female sex workers according to workplace. AB - OBJECTIVE To investigate differences in HIV infection- related risk practices by Female Sex Workers according to workplace and the effects of homophily on estimating HIV prevalence. METHODS Data from 2,523 women, recruited using Respondent-Driven Sampling, were used for the study carried out in 10 Brazilian cities in 2008-2009. The study included female sex workers aged 18 and over. The questionnaire was completed by the subjects and included questions on characteristics of professional activity, sexual practices, use of drugs, HIV testing, and access to health services. HIV quick tests were conducted. The participants were classified in two groups according to place of work: on the street or indoor venues, like nightclubs and saunas. To compare variable distributions by place of work, we used Chi-square homogeneity tests, taking into consideration unequal selection probabilities as well as the structure of dependence between observations. We tested the effect of homophily by workplace on estimated HIV prevalence. RESULTS The highest HIV risk practices were associated with: working on the streets, lower socioeconomic status, low regular smear test coverage, higher levels of crack use and higher levels of syphilis serological scars as well as higher prevalence of HIV infection. The effect of homophily was higher among sex workers in indoor venues. However, it did not affect the estimated prevalence of HIV, even after using a post-stratification by workplace procedure. CONCLUSIONS The findings suggest that strategies should focus on extending access to, and utilization of, health services. Prevention policies should be specifically aimed at street workers. Regarding the application of Respondent-Driven Sampling, the sample should be sufficient to estimate transition probabilities, as the network develops more quickly among sex workers in indoor venues. PMID- 25119938 TI - Senses of body image in adolescents in elementary school. AB - OBJECTIVE: To comprehend the perception of body image in adolescence. METHODS: A qualitative study was conducted with eight focus groups with 96 students of both sexes attending four public elementary school institutions in the city of Rio de Janeiro, Southeastern Brazil, in 2013. An interview guide with questions about the adolescents' feelings in relation to: their bodies, standards of idealized beauty, practice of physical exercise and sociocultural influences on self-image. In the data analysis we sought to understand and interpret the meanings and contradictions of narratives, understanding the subjects' context and reasons and the internal logic of the group. RESULTS: Three thematic categories were identified. The influence of media on body image showed the difficulty of achieving the perfect body and is viewed with suspicion in face of standards of beauty broadcast; the importance of a healthy body was observed as standards of beauty and good looks were closely linked to good physical condition and result from having a healthy body; the relationship between the standard of beauty and prejudice, as people who are not considered attractive, having small physical imperfections, are discriminated against and can be rejected or even excluded from society. CONCLUSIONS: The standard of perfect body propagated by media influences adolescents' self-image and, consequently, self-esteem and is considered an unattainable goal, corresponding to a standard of beauty described as artificial and unreal. However, it causes great suffering and discrimination against those who do not feel they are attractive, which can lead to health problems resulting from low self-esteem. PMID- 25119939 TI - Cumulative mortality of Aedes aegypti larvae treated with compounds. AB - OBJECTIVE To evaluate the larvicidal activity of Azadirachta indica, Melaleuca alternifolia, carapa guianensis essential oils and fermented extract of Carica papaya against Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae). METHODS The larvicide test was performed in triplicate with 300 larvae for each experimental group using the third larval stage, which were exposed for 24h. The groups were: positive control with industrial larvicide (BTI) in concentrations of 0.37 ppm (PC1) and 0.06 ppm (PC2); treated with compounds of essential oils and fermented extract, 50.0% concentration (G1); treated with compounds of essential oils and fermented extract, 25.0% concentration (G2); treated with compounds of essential oils and fermented extract, 12.5% concentration (G3); and negative control group using water (NC1) and using dimethyl (NC2). The larvae were monitored every 60 min using direct visualization. RESULTS No mortality occurred in experimental groups NC1 and NC2 in the 24h exposure period, whereas there was 100% mortality in the PC1 and PC2 groups compared to NC1 and NC2. Mortality rates of 65.0%, 50.0% and 78.0% were observed in the groups G1, G2 and G3 respectively, compared with NC1 and NC2. CONCLUSIONS The association between three essential oils from Azadirachta indica, Melaleuca alternifolia, Carapa guianensis and fermented extract of Carica papaya was efficient at all concentrations. Therefore, it can be used in Aedes aegypti Liverpool third larvae stage control programs. PMID- 25119940 TI - Principal components and generalized linear modeling in the correlation between hospital admissions and air pollution. AB - OBJECTIVE To analyze the association between concentrations of air pollutants and admissions for respiratory causes in children. METHODS Ecological time series study. Daily figures for hospital admissions of children aged < 6, and daily concentrations of air pollutants (PM10, SO2, NO2, O3 and CO) were analyzed in the Regiao da Grande Vitoria, ES, Southeastern Brazil, from January 2005 to December 2010. For statistical analysis, two techniques were combined: Poisson regression with generalized additive models and principal model component analysis. Those analysis techniques complemented each other and provided more significant estimates in the estimation of relative risk. The models were adjusted for temporal trend, seasonality, day of the week, meteorological factors and autocorrelation. In the final adjustment of the model, it was necessary to include models of the Autoregressive Moving Average Models (p, q) type in the residuals in order to eliminate the autocorrelation structures present in the components. RESULTS For every 10:49 MUg/m3 increase (interquartile range) in levels of the pollutant PM10 there was a 3.0% increase in the relative risk estimated using the generalized additive model analysis of main components seasonal autoregressive - while in the usual generalized additive model, the estimate was 2.0%. CONCLUSIONS Compared to the usual generalized additive model, in general, the proposed aspect of generalized additive model - principal component analysis, showed better results in estimating relative risk and quality of fit. PMID- 25119941 TI - Disparities in cervical and breast cancer mortality in Brazil. AB - OBJECTIVE To analyze cervical and breast cancer mortality in Brazil according to socioeconomic and welfare indicators. METHODS Data on breast and cervical cancer mortality covering a 30-year period (1980-2010) were analyzed. The data were obtained from the National Mortality Database, population data from the Brazilian Institute of Geography and Statistics database, and socioeconomic and welfare information from the Institute of Applied Economic Research. Moving averages were calculated, disaggregated by capital city and municipality. The annual percent change in mortality rates was estimated by segmented linear regression using the joinpoint method. Pearson's correlation coefficients were conducted between average mortality rate at the end of the three-year period and selected indicators in the state capital and each Brazilian state. RESULTS There was a decline in cervical cancer mortality rates throughout the period studied, except in municipalities outside of the capitals in the North and Northeast. There was a decrease in breast cancer mortality in the capitals from the end of the 1990s onwards. Favorable socioeconomic indicators were inversely correlated with cervical cancer mortality. A strong direct correlation was found with favorable indicators and an inverse correlation with fertility rate and breast cancer mortality in inner cities. CONCLUSIONS There is an ongoing dynamic process of increased risk of cervical and breast cancer and attenuation of mortality because of increased, albeit unequal, access to and provision of screening, diagnosis and treatment. PMID- 25119942 TI - Spatial study of homicide rates in the state of Bahia, Brazil, 1996-2010. AB - OBJECTIVE To analyze the spatial distribution of homicide mortality in the state of Bahia, Northeastern Brazil. METHODS Ecological study of the 15 to 39-year old male population in the state of Bahia in the period 1996-2010. Data from the Mortality Information System, relating to homicide (X85-Y09) and population estimates from the Brazilian Institute of Geography and Statistics were used. The existence of spatial correlation, the presence of clusters and critical areas of the event studied were analyzed using Moran's I Global and Local indices. RESULTS A non-random spatial pattern was observed in the distribution of rates, as was the presence of three clusters, the first in the north health district, the second in the eastern region, and the third cluster included townships in the south and the far south of Bahia. CONCLUSIONS The homicide mortality in the three different critical areas requires further studies that consider the socioeconomic, cultural and environmental characteristics in order to guide specific preventive and interventionist practices. PMID- 25119943 TI - Deported Mexican migrants: health status and access to care. AB - OBJECTIVE To describe the health status and access to care of forced-return Mexican migrants deported through the Mexico-United States border and to compare it with the situation of voluntary-return migrants. METHODS Secondary data analysis from the Survey on Migration in Mexico's Northern Border from 2012. This is a continuous survey, designed to describe migration flows between Mexico and the United States, with a mobile-population sampling design. We analyzed indicators of health and access to care among deported migrants, and compare them with voluntary-return migrants. Our analysis sample included 2,680 voluntary return migrants, and 6,862 deportees. We employ an ordinal multiple logistic regression model, to compare the adjusted odds of having worst self-reported health between the studied groups. RESULTS As compared to voluntary-return migrants, deportees were less likely to have medical insurance in the United States (OR = 0.05; 95%CI 0.04;0.06). In the regression model a poorer self perceived health was found to be associated with having been deported (OR = 1.71, 95%CI 1.52;1.92), as well as age (OR = 1.03, 95%CI 1.02;1.03) and years of education (OR = 0.94 95%CI 0.93;0.95). CONCLUSIONS According to our results, deportees had less access to care while in the United States, as compared with voluntary-return migrants. Our results also showed an independent and statistically significant association between deportation and having poorer self perceived health. To promote the health and access to care of deported Mexican migrants coming back from the United States, new health and social policies are required. PMID- 25119944 TI - Cross-cultural validity of the demand-control questionnaire: Swedish and Brazilian workers. AB - OBJECTIVE To evaluate the cross-cultural validity of the Demand-Control Questionnaire, comparing the original Swedish questionnaire with the Brazilian version. METHODS We compared data from 362 Swedish and 399 Brazilian health workers. Confirmatory and exploratory factor analyses were performed to test structural validity, using the robust weighted least squares mean and variance adjusted (WLSMV) estimator. Construct validity, using hypotheses testing, was evaluated through the inspection of the mean score distribution of the scale dimensions according to sociodemographic and social support at work variables. RESULTS The confirmatory and exploratory factor analyses supported the instrument in three dimensions (for Swedish and Brazilians): psychological demands, skill discretion and decision authority. The best-fit model was achieved by including an error correlation between work fast and work intensely (psychological demands) and removing the item repetitive work (skill discretion). Hypotheses testing showed that workers with university degree had higher scores on skill discretion and decision authority and those with high levels of Social Support at Work had lower scores on psychological demands and higher scores on decision authority. CONCLUSIONS The results supported the equivalent dimensional structures across the two culturally different work contexts. Skill discretion and decision authority formed two distinct dimensions and the item repetitive work should be removed. PMID- 25119945 TI - Tuberculosis Control Program and patient satisfaction, Rio de Janeiro, Brazil. AB - OBJECTIVE To evaluate factors associated with users' satisfaction in the Tuberculosis Control Program. METHODS A cross-sectional study of 295 patients aged >= 18 years, with two or more outpatient visits in the Tuberculosis Control Program, in five cities in the metropolitan region of Rio de Janeiro, RJ, Southeastern Brazil, in 2010. Considering an estimated population of 4,345 patients, the sampling plan included 15 health care units participating in the program, divided into two strata: units in Rio de Janeiro City, selected with probability proportional to the monthly average number of outpatient visits, and units in the other four cities. In the units, four temporal clusters of five patients each were selected with equal probability, totaling 300 patients. A questionnaire investigating the users' clinical and sociodemographic variables and aspects of care and service in the program relevant to user satisfaction was applied to the patients. Descriptive statistics about users and their satisfaction with the program were obtained, and the effects of factors associated with satisfaction were estimated. RESULTS Patients were predominantly males (57.7%), with a mean age of 40.9 and with low level of schooling. The mean treatment time was 4.1 months, mostly self-administered (70.4%). Additionally, 25.8% had previously been treated for tuberculosis. There was a high level of satisfaction, especially regarding medication provision, and respect to patients by the health professionals. Patients who were younger (<= 30), those on self administered treatment, and with graduate level, showed less satisfaction. Suggestions to improve the services include having more doctors (70.0%), and offering exams in the same place of attendance (55.1%). CONCLUSIONS Patient satisfaction with the Tuberculosis Control Program was generally high, although lower among younger patients, those with university education and those on self administered treatment. The study indicates the need for changes to structural and organizational aspects of care, and provides practical support for its improvement. PMID- 25119946 TI - Temporal trends and spatial distribution of unsafe abortion in Brazil, 1996-2012. AB - OBJECTIVE To analyze temporal trends and distribution patterns of unsafe abortion in Brazil. METHODS Ecological study based on records of hospital admissions of women due to abortion in Brazil between 1996 and 2012, obtained from the Hospital Information System of the Ministry of Health. We estimated the number of unsafe abortions stratified by place of residence, using indirect estimate techniques. The following indicators were calculated: ratio of unsafe abortions/100 live births and rate of unsafe abortion/1,000 women of childbearing age. We analyzed temporal trends through polynomial regression and spatial distribution using municipalities as the unit of analysis. RESULTS In the study period, a total of 4,007,327 hospital admissions due to abortions were recorded in Brazil. We estimated a total of 16,905,911 unsafe abortions in the country, with an annual mean of 994,465 abortions (mean unsafe abortion rate: 17.0 abortions/1,000 women of childbearing age; ratio of unsafe abortions: 33.2/100 live births). Unsafe abortion presented a declining trend at national level (R2: 94.0%, p < 0.001), with unequal patterns between regions. There was a significant reduction of unsafe abortion in the Northeast (R2: 93.0%, p < 0.001), Southeast (R2: 92.0%, p < 0.001) and Central-West regions (R2: 64.0%, p < 0.001), whereas the North (R2: 39.0%, p = 0.030) presented an increase, and the South (R2: 22.0%, p = 0.340) remained stable. Spatial analysis identified the presence of clusters of municipalities with high values for unsafe abortion, located mainly in states of the North, Northeast and Southeast Regions. CONCLUSIONS Unsafe abortion remains a public health problem in Brazil, with marked regional differences, mainly concentrated in the socioeconomically disadvantaged regions of the country. Qualification of attention to women's health, especially to reproductive aspects and attention to pre- and post-abortion processes, are necessary and urgent strategies to be implemented in the country. PMID- 25119948 TI - Interface between intellectual disability and mental health: hermeneutic review. AB - A literature review was conducted aiming to understand the interface between the Intellectual Disability and Mental Health fields and to contribute to mitigating the path of institutionalizing individuals with intellectual deficiencies. The so called dual diagnosis phenomenon remains underestimated in Brazil but is the object of research and specific public policy internationally. This phenomenon alerts us to the prevalence of mental health problems in those with intellectual disabilities, limiting their social inclusion. The findings reinforce the importance of this theme and indicate possible diagnostic invisibility of the development of mental illness in those with intellectual disabilities in Brazil, which may contribute to sustaining psychiatric institutionalization of this population. PMID- 25119949 TI - Phytotherapy in primary health care. AB - OBJECTIVE To characterize the integration of phytotherapy in primary health care in Brazil. METHODS Journal articles and theses and dissertations were searched for in the following databases: SciELO, Lilacs, PubMed, Scopus, Web of Science and Theses Portal Capes, between January 1988 and March 2013. We analyzed 53 original studies on actions, programs, acceptance and use of phytotherapy and medicinal plants in the Brazilian Unified Health System. Bibliometric data, characteristics of the actions/programs, places and subjects involved and type and focus of the selected studies were analyzed. RESULTS Between 2003 and 2013, there was an increase in publications in different areas of knowledge, compared with the 1990-2002 period. The objectives and actions of programs involving the integration of phytotherapy into primary health care varied: including other treatment options, reduce costs, reviving traditional knowledge, preserving biodiversity, promoting social development and stimulating inter-sectorial actions. CONCLUSIONS Over the past 25 years, there was a small increase in scientific production on actions/programs developed in primary care. Including phytotherapy in primary care services encourages interaction between health care users and professionals. It also contributes to the socialization of scientific research and the development of a critical vision about the use of phytotherapy and plant medicine, not only on the part of professionals but also of the population. PMID- 25119947 TI - Non-adherence to telemedicine interventions for drug users: systematic review. AB - OBJECTIVE To estimate rates of non-adherence to telemedicine strategies aimed at treating drug addiction. METHODS A systematic review was conducted of randomized controlled trials investigating different telemedicine treatment methods for drug addiction. The following databases were consulted between May 18, 2012 and June 21, 2012: PubMed, PsycINFO, SciELO, Wiley (The Cochrane Library), Embase, Clinical trials and Google Scholar. The Grading of Recommendations Assessment, Development and Evaluation was used to evaluate the quality of the studies. The criteria evaluated were: appropriate sequence of data generation, allocation concealment, blinding, description of losses and exclusions and analysis by intention to treat. There were 274 studies selected, of which 20 were analyzed. RESULTS Non-adherence rates varied between 15.0% and 70.0%. The interventions evaluated were of at least three months duration and, although they all used telemedicine as support, treatment methods differed. Regarding the quality of the studies, the values also varied from very poor to high quality. High quality studies showed better adherence rates, as did those using more than one technique of intervention and a limited treatment time. Mono-user studies showed better adherence rates than poly-user studies. CONCLUSIONS Rates of non-adherence to treatment involving telemedicine on the part of users of psycho-active substances differed considerably, depending on the country, the intervention method, follow up time and substances used. Using more than one technique of intervention, short duration of treatment and the type of substance used by patients appear to facilitate adherence. PMID- 25119951 TI - Knowing the previously unknown: identification of a methodological challenge for pharmacoepidemiology. PMID- 25119950 TI - Study of T helper (17) and T regulatory cells in psoriatic patients receiving live attenuated varicella vaccine therapy in a randomized controlled trial. AB - BACKGROUND: The use of live attenuated varicella vaccine (Varilrix((r))) as an adjuvant treatment in severe cases of psoriasis has recently been postulated. Its efficacy raised questions regarding its possible mechanisms of action. OBJECTIVE: To compare the efficacy and safety of combining Varilrix((r)) and cyclosporine to cyclosporine alone in the treatment of severe psoriasis. Furthermore, to study the expression of T helper (Th)17 and T regulatory (Tregs) cells before and after therapy. MATERIALS AND METHODS: This randomized controlled trial included 24 psoriatic patients, randomly divided into 2 groups (A and B). All patients received cyclosporine at a daily dose of 2.5 mg/kg/day. In addition, group A received 4 doses of Varilrix((r)) once/3 weeks, and group B received 4 doses of subcutaneous saline. Skin biopsies were obtained from all patients before and after therapy and from all controls for estimation of interleukin (IL)-17, IL-22 and Forkhead boxP3 (FoxP3) using RT-PCR. RESULTS: Group A patients showed a significantly higher % of clinical improvement (P = 0.011), which occurred earlier than group B. At baseline, levels of IL-17 and IL-22 were significantly higher while the level of FoxP3 was significantly lower in patients (P<0.001) compared to controls. After therapy, both groups showed significant reductions in both IL-17 and IL-22 levels, and significant elevation in FoxP3 (P<0.001). This change was significantly more evident in group A patients. CONCLUSION: Live attenuated varicella vaccine could play a role in the treatment of psoriasis when combined with low dose cyclosporine through accentuating the influence on the Th17/Treg balance. PMID- 25119952 TI - Causal inference using mixture models: a word of caution. PMID- 25119953 TI - Comparative effectiveness of patient-centered strategies to improve FDA medication guides. AB - BACKGROUND: Med Guides are the only Food and Drug Administration-regulated source of written patient information distributed with prescriptions drugs. Despite their potential value, studies have found them to have limited utility. OBJECTIVE: To evaluate the effectiveness of patient-centered strategies for the design of Med Guides to improve comprehension. DESIGN: A cross-sectional, randomized trial. SETTING: Two primary care clinics in Chicago, Illinois; one based in a public university hospital and the other within a private academic medical center. PATIENTS: A total of 1003 adults aged 18-85 years. INTERVENTION: The format and layout of content from 3 typical Med Guides (by reading difficulty, length, exposure) were modified several ways to promote information accessibility. Working with patients, the 3 most preferred versions were evaluated. The first used 2 columns to organize content (Column), a second mimicked over-the-counter "Drug Facts" labeling (Drug Facts), and the third followed health literacy best practices using a simple table format (Health Literacy prototype). MEASURES: Tailored comprehension assessment of content from 3 representative Med Guides. RESULTS: Comprehension was significantly greater for all 3 prototypes compared with the current standard (all P<0.001). The Health Literacy prototype consistently demonstrated the highest comprehension scores, and in multivariable analyses, outperformed both the Drug Facts [beta=-4.43, 95% confidence interval (CI), -6.21 to -2.66] and Column (beta=-4.04, 95% CI, -5.82 to -2.26) prototypes. Both older age (older than 60 y: beta=-10.54, 95% CI, 15.12 to -5.96), low and marginal literacy skills were independently associated with poorer comprehension (low: beta=-31.92, 95% CI, -35.72 to -28.12; marginal: beta=-12.91, 95% CI, -16.01 to -9.82). CONCLUSIONS: The application of evidence based practices to the redesign of Med Guides significantly improved patient comprehension. Although some age and literacy disparities were reduced with the Health Literacy format in particular, both older age and low literacy remained independently associated with poorer comprehension. More aggressive strategies will likely be needed to gain assurances that all patients are informed about their prescribed medications. TRIAL REGISTRATION: Clinical Trials.Gov #NCT01731405. PMID- 25119954 TI - Elderly breast and colorectal cancer patients' clinical course: patient and contextual influences. AB - BACKGROUND: The social and medical environments that surround people are each independently associated with their cancer course. The extent to which these characteristics may together mediate patients' cancer care and outcomes is not known. METHODS: Using multilevel methods and data, we studied elderly breast and colorectal cancer patients (level I) within urban social (level II: ZIP code tabulation area) and health care (level III: hospital service area) contexts. We sought to determine (1) which, if any, observable social and medical contextual attributes were associated with patient cancer outcomes after controlling for observable patient attributes, and (2) the magnitude of residual variation in patient cancer outcomes at each level. RESULTS: Numerous patient attributes and social area attributes, including poverty, were associated with unfavorable patient cancer outcomes across the full clinical cancer continuum for both cancers. Health care area attributes were not associated with patient cancer outcomes. After controlling for observable covariates at all 3 levels, there was substantial residual variation in patient cancer outcomes at all levels. CONCLUSIONS: After controlling for patient attributes known to confer risk of poor cancer outcomes, we find that neighborhood socioeconomic disadvantage exerts an independent and deleterious effect on residents' cancer outcomes, but the area supply of the specific types of health care studied do not. Multilevel interventions targeted at cancer patients and their social areas may be useful. We also show substantial residual variation in patient outcomes across social and health care areas, a finding potentially relevant to traditional small area variation research methods. PMID- 25119955 TI - Prescription opioid use among disabled Medicare beneficiaries: intensity, trends, and regional variation. AB - BACKGROUND: Prescription opioid use and overdose deaths are increasing in the United States. Among disabled Medicare beneficiaries under the age of 65, the rise in musculoskeletal conditions as qualifying diagnoses suggests that opioid analgesic use may be common and increasing, raising safety concerns. METHODS: From a 40% random-sample Medicare denominator, we identified fee-for-service beneficiaries under the age of 65 and created annual enrollment cohorts from 2007 to 2011 (6.4 million person-years). We obtained adjusted, annual opioid use measures: any use, chronic use (>= 6 prescriptions), intensity of use [daily morphine equivalent dose (MED)], and opioid prescribers per user. Geographic variation was studied across Hospital Referral Regions. RESULTS: Most measures peaked in 2010. The adjusted proportion with any opioid use was 43.9% in 2007, 44.7% in 2010, and 43.7% in 2011. The proportion with chronic use rose from 21.4% in 2007 to 23.1% in 2011. Among chronic users: mean MED peaked at 81.3 mg in 2010, declining to 77.4 mg in 2011; in 2011, 19.8% received >= 100 mg MED; 10.4% received >= 200 mg. In 2011, Hospital Referral Region-level measures varied broadly (5th-95th percentile): any use: 33.0%-58.6%, chronic use: 13.9%-36.6%; among chronic users, mean MED: 45 mg-125 mg; mean annual opioid prescribers: 2.4 3.7. CONCLUSIONS: Among these beneficiaries, opioid use was common. Although intensity stabilized, the population using opioids chronically grew. Variation shows a lack of a standardized approach and reveals regions with mean MED at levels associated with overdose risk. Future work should assess outcomes, chronic use predictors, and policies balancing pain control and safety. PMID- 25119956 TI - Nontraumatic paecilomyces anterior segment infection: a pathognomonic clinical appearance. AB - PURPOSE: The aim of this study was to review a series of consecutive cases of corneal and scleral infection by Paecilomyces spp. and to identify features of clinical presentation and assess treatment modalities. METHODS: This retrospective review of a case series included 22 patients with nontraumatic Paecilomyces anterior segment infections who were seen in a tertiary referral practice. Outcome measures were the number of eyes that were lost and visual acuity in eyes that were saved. RESULTS: Twenty-two patients with Paecilomyces corneal or scleral infection with no significant history of trauma or surgery were identified over a 20-year period. Two distinct clinical presentations were noted with 17 presenting with corneal infection and 5 initially presenting with scleral infection, and all demonstrated a classical endothelial plaque and deep stromal infiltrate. Almost all required single or multiple anterior segment reconstructive surgeries together with systemic and topical antifungal agents. The first 10 patients were treated with amphotericin B, whereas the remaining 12 patients were treated with voriconazole and 21 of 22 patients underwent surgery. Paecilomyces spp. was identified from most intraocular specimens although corneal fungal growth was noted only from deep corneal biopsies or corneal buttons removed during corneal transplantation. Outcomes were better in the last 12 patients treated with voriconazole. CONCLUSIONS: Nontraumatic Paecilomyces anterior segment infection presents with a pathognomonic clinical picture when the cornea is the initial site of infection and later in scleral infections. Early identification and aggressive treatment with extirpative surgery and voriconazole may result in retention of the eye with useful vision. PMID- 25119957 TI - Descemet membrane detachment after Nd: YAG laser capsulotomy in a patient with fuchs dystrophy. AB - PURPOSE: Descemet membrane detachment (DMD) is uncommon. It most frequently occurs as a complication of intraocular surgery. The aim of this study was to report a case of DMD after neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy in a patient with Fuchs dystrophy. METHODS: We describe the case of an 89-year-old man suffering from Fuchs dystrophy, who underwent cataract surgery on his left eye. Three years later, the patient presented with posterior capsule opacification, which was treated using Nd:YAG laser capsulotomy. The day after the procedure, the patient came back for emergency treatment because of an acute reduction in his vision caused by a DMD. RESULTS: Fifteen days after an initial treatment involving the injection of air into the anterior chamber coupled with ocular paracentesis, clinical examination revealed a significant improvement in visual acuity, reduction in corneal edema, and reattachment of Descemet membrane. These findings were confirmed using anterior segment optical coherence tomography. CONCLUSIONS: To our knowledge, this is the first reported case of DMD after Nd:YAG laser capsulotomy. PMID- 25119958 TI - Wound healing process after corneal stromal thinning observed with anterior segment optical coherence tomography. AB - PURPOSE: The aim of this study was to observe the wound healing process after corneal stromal thinning by using anterior segment optical coherence tomography (AS-OCT) and a slit lamp. METHODS: Four patients with corneal stromal thinning (2 patients: corneal iron foreign bodies; 2 patients: keratitis) were included. Serial AS-OCT and slit-lamp examinations were used to follow up the progress of these patients. The thicknesses of the whole cornea and the corneal stroma were measured with AS-OCT and compared with the findings observed during the slit-lamp examination. RESULTS: AS-OCT showed that epithelial hypertrophy and hyperplasia initially occurred in the area of the corneal stromal thinning; subsequently, scar tissue formed in the area with an improvement in the thickness of the corneal stroma. This wound healing process was observed in all 4 patients. The scar tissue initially appeared opaque on slit-lamp examination and was characterized by a high signal produced on AS-OCT, which was different from the normal corneal stroma. The scar tissue gradually appeared clear on slit-lamp examination; however, the high signal on AS-OCT remained. CONCLUSIONS: AS-OCT can be used to detect the wound healing process of corneal stromal thinning. PMID- 25119959 TI - Lens status as the single most important factor in endothelium protection after vitreous surgery: a prospective study. AB - PURPOSE: The aim of this study was to evaluate the effect of vitreous surgery on the corneal endothelium. METHODS: A total of 113 eyes undergoing pars plana vitrectomy for variable indications at a tertiary care center were included prospectively. The mean age was 41 years (range, 9-84 years), and 60% were male. The endothelial cell count was measured preoperatively and on postoperative day 1, 30, 90, and 180. The rate of endothelial cell loss was measured and analysis performed based on gauge of surgery, lens status, and vitreous substitute used. RESULTS: About 7.6% of endothelial cells were lost at postoperative day 1. This rate had decreased to 2.5% in the first 30 days, 1.5% between days 30 and 90, and 1.4% between days 90 and 180. Significant difference in endothelial cell loss was noted on day 1 between phakic (7.2%), pseudophakic (6.4%), and aphakic (11.4%) eyes with similar results at 6 months. There was no significant difference between the gauges of surgery (20 G vs. 23 G) or the vitreous substitutes used (air vs. gas vs. silicone oil) on day 1 or at 6 months. CONCLUSIONS: Endothelial decompensation is an important complication of vitreoretinal surgery. Precautions should be taken in aphakics and patients requiring anterior segment manipulation. Although there is immediate cell loss, the rate of cell loss approaches normative values with time. PMID- 25119960 TI - Healing rate of corneal erosions: comparison of the effect of chloramphenicol eye drops and ointment and high-concentration hyaluronic acid in an animal model. AB - PURPOSE: The aim of this study was to compare the effect of chloramphenicol eye drops or ointment, high-concentration hyaluronic acid, or no treatment on reepithelialization of corneal erosions in an experimental model. METHODS: Uniform 6-mm corneal erosions were created in 23 rabbit eyes. The rabbits were randomized to 4 treatment groups: (1) chloramphenicol eye drops group, (2) chloramphenicol ointment, (3) hyaluronic acid 2.3%, and (4) untreated. Treatment was administered every 8 hours until reepithelialization occurred. Eyes were photographed every 8 hours with a cobalt blue-filtered light with fluorescein drops until reepithelialization occurred. The area of the erosion at each time point was analyzed. RESULTS: There were no significant differences in the reepithelialization of the corneal erosion among the 3 treatment groups (72-75 hours, P > 0.05). The time was significantly shorter (51 hours) for the control untreated group (P = 0.005). CONCLUSIONS: The use of chloramphenicol in the form of eye drops or ointment for prophylaxis in corneal erosions has a similar effect on the healing rate of the erosion. Both forms of the antibiotic and high concentration hyaluronic acid had an effect of slowing down the healing of the erosion when compared with when no treatment was given. Therefore, the decision to treat erosions with eye drops or ointment can be based on the patient's comfort. PMID- 25119962 TI - Effects of subconjunctival tocilizumab versus bevacizumab in treatment of corneal neovascularization in rabbits. AB - PURPOSE: The aim of this study was to compare the antiangiogenic effects of subconjunctival application of bevacizumab and tocilizumab on the regression of corneal neovascularization (NV) in rabbits. METHODS: Corneal neovascularization was induced in 48 eyes of 24 rabbits. Seven days after suture placement, the rabbits were divided into 4 groups of 6 rabbits each and treated subconjunctivally with 0.1 mL balanced salt solution (group 1), 0.1 mL tocilizumab (0.25 mg per 0.1 mL and 2.5 mg per 0.1 mL, groups 2 and 3), or 0.1 mL bevacizumab (2.5 mg per 0.1 mL) (group 4). Digital photographs of the eyes were obtained and the surface areas of corneal neovascularization were measured on days 7 and 14 after subconjunctival injections. On days 7 and 14, 3 rabbits were randomly chosen and the eyes were extracted. Half of the corneal specimens were analyzed histopathologically, and the other half were used to measure the concentrations of vascular endothelial growth factor (VEGF) and IL-6 using a multiplex bead assay, and the levels were compared with those of the controls. RESULTS: The surface areas of induced corneal neovascularization were significantly smaller in groups 3 and 4 (2.5 mg of tocilizumab and 2.5 mg of bevacizumab) compared with the control group on days 7 and 14 (P < 0.05). Group 2 did not show significant difference from the control group on days 7 and 14. There were no differences observed in the reduced neovascularization areas in groups 3 and 4 on days 7 and 14. The concentrations of VEGF in groups 3 and 4 were significantly lower than in the control group, and IL-6 mRNA levels were significantly lower in group 3 than in the other groups (P < 0.001) on days 7 and 14. Immunohistochemical analysis confirmed the reduced expression of VEGF in all 3 experimental groups compared with the control group. CONCLUSIONS: An antiangiogenic effect was observed after subconjunctival injection of 2.5 mg tocilizumab to an extent similar to that seen with 2.5 mg bevacizumab, which indicates that subconjunctival application of tocilizumab is effective for the inhibition of corneal neovascularization. PMID- 25119963 TI - In vivo confocal microscopic features of corneal pseudodendritic lesions in tyrosinemia type II. AB - PURPOSE: To report the clinical and in vivo confocal microscopic (IVCM) findings of corneal deposits in a patient with tyrosinemia type II. METHODS: The pretreatment and 1-month posttreatment slit-lamp examination and IVCM findings of a patient with tyrosinemia type II are described. RESULTS: A 12-year-old girl diagnosed with tyrosinemia type II was evaluated for photophobia and bilateral ocular discomfort of 1-year duration. The patient had been placed on topical acyclovir treatment with the diagnosis of recurrent bilateral herpetic keratitis during the previous 12 months. Slit-lamp examination revealed bilateral dendritiform epithelial lesions in the central cornea, which stained poorly with fluorescein. IVCM highlighted multiple hyperreflective linear crystalline deposits at the level of superficial epithelium. One month after discontinuation of acyclovir treatment and initiation of a protein-restricted diet therapy, improvement in the patient's symptoms and regression of corneal epithelial lesions was noted. Reduction in the extent of corneal deposits was also confirmed with IVCM. CONCLUSIONS: Corneal involvement, secondary to hereditary tyrosinemia type II, is characterized by pseudodendritic epithelial lesions on slit-lamp examination and hyperreflective linear deposits in the superficial epithelium using IVCM. These lesions may regress expeditiously with a low-protein diet. IVCM may be a useful tool in the differential diagnosis of this disorder by highlighting the crystalline structures in the superficial epithelial layers and also in evaluating the response to the treatment in patients with tyrosinemia type II. PMID- 25119961 TI - Corneal graft rejection 10 years after penetrating keratoplasty in the cornea donor study. AB - PURPOSE: The aim of this study was to assess the effect of donor and recipient factors on corneal allograft rejection and evaluate whether a rejection event was associated with graft failure. METHODS: One thousand ninety subjects undergoing penetrating keratoplasty for a moderate risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) were followed for up to 12 years. Associations of baseline recipient and donor factors with the occurrence of a rejection event were assessed in univariate and multivariate proportional hazards models. RESULTS: Among 651 eyes with a surviving graft at 5 years, the 10-year graft failure (+/-99% confidence interval) rates were 12% +/- 4% among eyes with no rejection events in the first 5 years, 17% +/- 12% in eyes with at least 1 probable, but no definite rejection event, and 22% +/- 20% in eyes with at least 1 definite rejection event. The only baseline factor significantly associated with a higher risk of definite graft rejection was a preoperative history of glaucoma, particularly when previous glaucoma surgery had been performed and glaucoma medications were being used at the time of transplant (10-year incidence 35% +/- 23% compared with 14% +/- 4% in eyes with no history of glaucoma/intraocular pressure treatment, P = 0.008). CONCLUSIONS: Patients who experienced a definite rejection event frequently developed graft failure raising important questions as to how we might change acute and long-term corneal graft management. Multivariate analysis indicated that previous use of glaucoma medications and glaucoma filtering surgery was a significant risk factor related to a definite rejection event. PMID- 25119964 TI - Changes in color vision and contrast sensitivity after descemet membrane endothelial keratoplasty for fuchs endothelial dystrophy. AB - PURPOSE: The aim of this study is to evaluate contrast sensitivity, color vision, and subjective patient satisfaction after Descemet membrane endothelial keratoplasty (DMEK) in patients with bilateral Fuchs endothelial dystrophy (FED). METHODS: From a group of 500 DMEK surgeries performed in our center, patients with a history of bilateral FED and unilateral DMEK were identified. A total of 29 patients were included in the study and divided into 2 groups: phakic (n = 12) and pseudophakic unilateral DMEK (n = 17) and their contralateral, untreated FED affected eye. In addition, a control group of 10 healthy eyes of 10 patients was included. Pelli-Robson contrast sensitivity and Farnsworth-Munsell 100 hue color vision tests were performed. Subjective optical quality was graded with a questionnaire. RESULTS: Compared with untreated FED-affected eyes, best spectacle corrected visual acuity was higher after DMEK in phakic and pseudophakic eyes (P = 0.030 and P < 0.001, respectively); a similar result was obtained for contrast sensitivity (P < 0.001 and P < 0.001, respectively). Color vision did not differ between untreated FED-affected and DMEK-operated eyes in the phakic group (P = 0.802) and the pseudophakic group (P = 0.227). Subjective optical quality was better in DMEK-operated eyes than in untreated FED-affected eyes in the phakic group (P < 0.001) and in the pseudophakic group (P < 0.001). CONCLUSIONS: In FED, DMEK may not only be effective for obtaining a higher visual acuity but particularly improving the contrast sensitivity may also lead to better subjective optical performance. Although frequently mentioned spontaneously by patients, an objective change in color vision could not be substantiated. Hence, quantifying contrast sensitivity before surgery may aid in the decision for surgery, and in the evaluation of surgical outcome. PMID- 25119965 TI - Phytochrome-interacting transcription factors PIF4 and PIF5 induce leaf senescence in Arabidopsis. AB - Plants initiate senescence to shed photosynthetically inefficient leaves. Light deprivation induces leaf senescence, which involves massive transcriptional reprogramming to dismantle cellular components and remobilize nutrients. In darkness, intermittent pulses of red light can inhibit senescence, likely via phytochromes. However, the precise molecular mechanisms transducing the signals from light perception to the inhibition of senescence remain elusive. Here, we show that in Arabidopsis, dark-induced senescence requires phytochrome interacting transcription factors PIF4 and PIF5 (PIF4/PIF5). ELF3 and phytochrome B inhibit senescence by repressing PIF4/PIF5 at the transcriptional and post translational levels, respectively. PIF4/PIF5 act in the signalling pathways of two senescence-promoting hormones, ethylene and abscisic acid, by directly activating expression of EIN3, ABI5 and EEL. In turn, PIF4, PIF5, EIN3, ABI5 and EEL directly activate the expression of the major senescence-promoting NAC transcription factor ORESARA1, thus forming multiple, coherent feed-forward loops. Our results reveal how classical light signalling connects to senescence in Arabidopsis. PMID- 25119966 TI - Accuracy of magnetic resonance imaging in planning the osseous resection margins of bony tumours in the proximal femur: based on coronal T1-weighted versus STIR images. AB - OBJECTIVE: Assessment of the extent of tumours using magnetic resonance imaging (MRI) is the basis for bone resection in limb-salvage surgery. We aimed to compare the accuracy of T1-weighted MRI and STIR sequences in measuring the extent of proximal femoral tumours, using the macroscopic specimens as the gold standard for comparison. MATERIALS AND METHODS: We compared single coronal T1 weighted with STIR sequences in 34 proximal femoral tumours, using bivalved resected macroscopic tumours for comparison. After randomisation, four observers measured longitudinal osseous tumour extent using MRI and specimen photographs on two separate occasions, 3 weeks apart. RESULTS: There were 25 metastatic tumours, 8 chondrosarcomas and 1 myeloma. Eight patients presented with pathological fractures. The Pearson's correlation coefficient for comparison of T1 with macroscopic tumours was 0.91 (95% confidence interval [CI]: 0.83 to 0.96) for all observers and 0.90 (95% CI: 0.81 to 0.95) for STIR images. This difference was not statistically significant, and T1 and STIR sequence measurements had similar precision and accuracy. Bland-Altman plots showed T1-weighted imaging to be unbiased, whereas STIR sequences were biased and had systematic error. Moreover, STIR measurements overestimated tumour size by 6.4 mm (95% CI: -26.9 to 39.7 mm) and 2 patients were outliers. T1 measurements were closer to the macroscopic measurements with a mean difference of 1.3 mm (95% CI: -28.9 mm to 31.5 mm), with 3 patients falling outside of this. The variance was greater for STIR measurements. This difference between T1 and STIR measurements was statistically significant (p = 0.000003). The intra-observer reliability between separate measurements for MRI and specimen photographs achieved interclass correlation coefficients of 0.97, 0.96 and 0.95 (T1, STIR and macroscopic tumour respectively). T1 had greater interobserver correlation than for STIR and macroscopic tumour measurements (0.88 vs 0.85 and 0.85 respectively). These differences in interclass correlation were not statistically significant. CONCLUSION: This study has shown T1-weighted MRI sequences to be unbiased compared with STIR sequences at determining intra-osseous tumour extent. STIR overestimates the length of bone tumours. T1 is therefore preferred for pre operative planning for the resection of bone tumours. PMID- 25119967 TI - FGFR3-related condition: a skeletal dysplasia with similarities to thanatophoric dysplasia and SADDAN due to Lys650Met. AB - Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for six related skeletal dysplasia conditions: achondroplasia, hypochondroplasia, thanatophoric dysplasia types 1 and 2, SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), and platyspondylic lethal skeletal dysplasia, San Diego type. This group of disorders has very characteristic clinical and radiologic features, which distinguish them from other skeletal dysplasias. They display a spectrum of severity in the skeletal findings, ranging from relatively mild hypochondroplasia to lethal thanatophoric dysplasia. We report a patient who has the missense FGFR3 mutation, Lys650Met, previously reported in association only with SADDAN, who exhibits some findings similar to both thanatophoric dysplasia (types 1 and 2) in addition to those findings characteristic of SADDAN. PMID- 25119969 TI - PMCA4 (ATP2B4) mutation in familial spastic paraplegia. AB - Familial spastic paraplegia (FSP) is a heterogeneous group of disorders characterized primarily by progressive lower limb spasticity and weakness. More than 50 disease loci have been described with different modes of inheritance. In this study, we identified a novel missense mutation (c.803G>A, p.R268Q) in the plasma membrane calcium ATPase (PMCA4, or ATP2B4) gene in a Chinese family with autosomal dominant FSP using whole-exome sequencing and confirmed with Sanger sequencing. This mutation co-segregated with the phenotype in the six family members studied and is predicted to be pathogenic when multiple deleteriousness predictions were combined. This novel R268Q mutation was not present in over 7,000 subjects in public databases, and over 1,000 Han Chinese in our database. Prediction of potential functional consequence of R268Q mutation on PMCA4 by computational modeling revealed that this mutation is located in protein aggregation-prone segment susceptible to protein misfolding. Analysis for thermodynamic protein stability indicated that this mutation destabilizes the PMCA4 protein structure with higher folding free energy. As PMCA4 functions to maintain neuronal calcium homeostasis, our result showed that calcium dysregulation may be associated with the pathogenesis of FSP. PMID- 25119968 TI - The role of nibrin in doxorubicin-induced apoptosis and cell senescence in Nijmegen Breakage Syndrome patients lymphocytes. AB - Nibrin plays an important role in the DNA damage response (DDR) and DNA repair. DDR is a crucial signaling pathway in apoptosis and senescence. To verify whether truncated nibrin (p70), causing Nijmegen Breakage Syndrome (NBS), is involved in DDR and cell fate upon DNA damage, we used two (S4 and S3R) spontaneously immortalized T cell lines from NBS patients, with the founding mutation and a control cell line (L5). S4 and S3R cells have the same level of p70 nibrin, however p70 from S4 cells was able to form more complexes with ATM and BRCA1. Doxorubicin-induced DDR followed by cell senescence could only be observed in L5 and S4 cells, but not in the S3R ones. Furthermore the S3R cells only underwent cell death, but not senescence after doxorubicin treatment. In contrary to doxorubicin treatment, cells from all three cell lines were able to activate the DDR pathway after being exposed to gamma-radiation. Downregulation of nibrin in normal human vascular smooth muscle cells (VSMCs) did not prevent the activation of DDR and induction of senescence. Our results indicate that a substantially reduced level of nibrin or its truncated p70 form is sufficient to induce DNA damage dependent senescence in VSMCs and S4 cells, respectively. In doxorubicin treated S3R cells DDR activation was severely impaired, thus preventing the induction of senescence. PMID- 25119970 TI - Posttranslational protein modifications by reactive nitrogen and chlorine species and strategies for their prevention and elimination. AB - Proteins are subject to various posttranslational modifications, some of them being undesired from the point of view of metabolic efficiency. Prevention of such modifications is expected to provide new means of therapy of diseases and decelerate the process of aging. In this review, modifications of proteins by reactive nitrogen species and reactive halogen species, is briefly presented and means of prevention of these modifications and their sequelae are discussed, including the denitrase activity and inhibitors of myeloperoxidase. PMID- 25119974 TI - Bromide: a pressing issue to address in China's shale gas extraction. PMID- 25119972 TI - Targeting BRAF mutant metastatic colorectal cancer: clinical implications and emerging therapeutic strategies. AB - Increasing knowledge of the underlying signaling pathways and molecular defects involved in colorectal cancer growth or progression enabled the discovery of several prognostic and predictive biomarkers, leading to the development of novel molecularly targeted therapies. The mitogen-activated protein kinase (MAPK) signaling pathway plays a critical role in colorectal cancer progression. Mutations in BRAF, a principal effector of Ras in this signaling cascade, are found in 10 % of colorectal cancer and play a clear pathogenic role, particularly in patients with metastatic disease. Intense efforts have therefore focused on targeting BRAF as an oncogenic driver, with mixed early results. This article summarizes the molecular and clinical features of BRAF mutant colorectal cancer, the prognostic and predictive role of BRAFV600E mutation in colorectal cancer, initial clinical trial results in targeting BRAFV600E, and the more recent preclinical insights into potential mechanisms of resistance to BRAF inhibition that have now led to a number of rationale-driven combination therapeutic strategies. PMID- 25119973 TI - Rebiopsy during disease progression in patients treated by TKI for oncogene addicted NSCLC. AB - All lung cancer patients with mutant epidermal growth factor receptor (EGFR) or rearranged EML4-ALK eventually develop acquired resistance to treatment. Rebiopsy may give insight into the resistance mechanisms and direct further lines of treatment. Here, we evaluate the potential interest and limitations of rebiopsy. Patients with mutant EGFR or rearranged EML4-ALK non-small cell lung cancer (NSCLC) and acquired resistance to tyrosine kinase inhibitors were included in a retrospective study to determine the percentage of patients who underwent rebiopsy and whether rebiopsy would have been possible, or not, in the remaining patients. In a cohort of 84 patients from 6 institutions, a biopsy had been performed in 39 cases. Biopsy samples were sufficient for histopathological or cytological examination in 35 cases (89.7 %). Complete or partial response had been observed in 84.5 % of patients whose cancer further progressed and who underwent rebiopsy. A biopsy could have been considered in 30 of the 45 remaining patients. Those with brain (N = 9) and bone (N = 2) metastases and/or with contraindications (N = 6) were excluded (two patients had both brain metastases and a contraindication). The rebiopsy target was thoracic in 62 % of cases and on distant metastases in 38 % of cases. Patients with NSCLC and an activating mutation could undergo a rebiopsy in 72 % of cases. A response to treatment does not preclude the possibility of rebiopsy at the time of progression. PMID- 25119975 TI - Synthesis of colloidal microgels using oxygen-controlled flow lithography. AB - We report a synthesis approach based on stop-flow lithography (SFL) for fabricating colloidal microparticles with any arbitrary 2D-extruded shape. By modulating the degree of oxygen inhibition during synthesis, we achieved previously unattainable particle sizes. Brownian diffusion of colloidal discs in bulk suggests the out-of-plane dimension can be as small as 0.8 MUm, which agrees with confocal microscopy measurements. We measured the hindered diffusion of microdiscs near a solid surface and compared our results to theoretical predictions. These colloidal particles can also flow through physiological microvascular networks formed by endothelial cells undergoing vasculogensis under minimal hydrostatic pressure (~5 mm H2O). This versatile platform creates future opportunities for on-chip parametric studies of particle geometry effects on particle passage properties, distribution and cellular interactions. PMID- 25119976 TI - Treating the violent patient with psychosis or impulsivity utilizing antipsychotic polypharmacy and high-dose monotherapy. AB - Insufficient treatment of psychosis often manifests as violent and aggressive behaviors that are dangerous to the patient and others, and that warrant treatment strategies which are not considered first-line, evidence-based practices. Such treatment strategies include both antipsychotic polypharmacy (simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy. Here we discuss the hypothesized neurobiological substrates of various types of violence and aggression, as well as providing arguments for the use of antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional neurocircuitry in the subpopulation of patients that is treatment-resistant, violent, and aggressive. In this review, we focus primarily on the data supporting the use of second-generation, atypical antipsychotics both at high doses and in combination with other antipsychotics. PMID- 25119977 TI - Zirconium complexes of phenylene-bridged {ONSO} ligands: coordination chemistry and stereoselective polymerization of rac-lactide. AB - Sequential tetradentate dianionic thio-imine diphenolate ligands featuring an ortho-phenylene core and their zirconium complexes are described for the first time. Ligands that include different combinations of bulky-alkyl groups and halo groups on the two phenol arms were prepared by a substitution/condensation reaction sequence. An unexpected fac-fac wrapping mode was found in the solid state for the ligands in the octahedral [{ONSO}Zr(O(t)Bu)2] complexes. The complexes were all fluxional, and the barrier for enantiomer interconversion was found to depend on the phenolate substituents. The complexes were found to catalyze the polymerization of rac-lactide to poly(lactic acid) in solution with polymer tacticities varying from heterotactic to atactic which showed correlation to the nature of phenolate substituents but not to the degree of complex fluxionality. PMID- 25119978 TI - Binding free energy based structural dynamics analysis of HIV-1 RT RNase H inhibitor complexes. AB - Accurate prediction of binding free energies associated with small molecules binding to a receptor is a major challenge in drug design processes. To achieve this goal many computational methods have been developed ranging from highly efficient empirical based docking schemes to high accuracy methods based on e.g. free energy calculations. In this study, binding affinity predictions for a set of HIV-1 RNase H inhibitors have been performed using MM-PB(GB)/SA methods. The current study describes in detail how the choice of initial ligand structures, e.g. protonation states, impacts the predicted ranking of the compounds. In addition we study the structural dynamics of the RNase H complexes using molecular dynamics. The role of each residue contribution to the overall binding free energy is also explored and used to explain the variations in the inhibition potency. The results reported here can be useful for design of small molecules against RNase H activity in the development of effective drugs for HIV treatment. PMID- 25119979 TI - Perspectives in Pediatric Pathology, Chapter 12. Congenital Epididymal Anomalies. PMID- 25119980 TI - Remember that? Or does it just seem familiar? A sophisticated test for assessing memory in humans and animals reveals a specific cognitive impairment following general anesthesia in infancy. PMID- 25119982 TI - Local coding based matching kernel method for image classification. AB - This paper mainly focuses on how to effectively and efficiently measure visual similarity for local feature based representation. Among existing methods, metrics based on Bag of Visual Word (BoV) techniques are efficient and conceptually simple, at the expense of effectiveness. By contrast, kernel based metrics are more effective, but at the cost of greater computational complexity and increased storage requirements. We show that a unified visual matching framework can be developed to encompass both BoV and kernel based metrics, in which local kernel plays an important role between feature pairs or between features and their reconstruction. Generally, local kernels are defined using Euclidean distance or its derivatives, based either explicitly or implicitly on an assumption of Gaussian noise. However, local features such as SIFT and HoG often follow a heavy-tailed distribution which tends to undermine the motivation behind Euclidean metrics. Motivated by recent advances in feature coding techniques, a novel efficient local coding based matching kernel (LCMK) method is proposed. This exploits the manifold structures in Hilbert space derived from local kernels. The proposed method combines advantages of both BoV and kernel based metrics, and achieves a linear computational complexity. This enables efficient and scalable visual matching to be performed on large scale image sets. To evaluate the effectiveness of the proposed LCMK method, we conduct extensive experiments with widely used benchmark datasets, including 15-Scenes, Caltech101/256, PASCAL VOC 2007 and 2011 datasets. Experimental results confirm the effectiveness of the relatively efficient LCMK method. PMID- 25119981 TI - Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii infection in mice. AB - Cryptococcus gattii is a fungal pathogen that can cause life-threatening respiratory and disseminated infections in immune-competent and immune-suppressed individuals. Currently, there are no standardized vaccines against cryptococcosis in humans, underlying an urgent need for effective therapies and/or vaccines. In this study, we evaluated the efficacy of intranasal immunization with C. gattii cell wall associated (CW) and/or cytoplasmic (CP) protein preparations to induce protection against experimental pulmonary C. gattii infection in mice. BALB/c mice immunized with C. gattii CW and/or CP protein preparations exhibited a significant reduction in pulmonary fungal burden and prolonged survival following pulmonary challenge with C. gattii. Protection was associated with significantly increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and increased C. gattii-specific antibody production in immunized mice challenged with C. gattii. A number of immunodominant proteins were identified following immunoblot analysis of C. gattii CW and CP protein preparations using sera from immunized mice. Immunization with a combined CW and CP protein preparation resulted in an early increase in pulmonary T cell infiltrates following challenge with C. gattii. Overall, our studies show that C. gattii CW and CP protein preparations contain antigens that may be included in a subunit vaccine to induce prolonged protection against pulmonary C. gattii infection. PMID- 25119983 TI - Diversity of selected Lupinus angustifolius L. genotypes at the phenotypic and DNA level with respect to microscopic seed coat structure and thickness. AB - The paper investigates seed coat characteristics (as a percentage of overall seed diameter) in Lupinus angustifolius L., a potential forage crop. In the study ten L. angustifolius genotypes, including three Polish cultivars, two Australian cultivars, three mutants originated from cv. 'Emir', and one Belarusian and one Australian breeding line were evaluated. The highest seed coat percentage was recorded in cultivars 'Sonet' and 'Emir'. The lowest seed coat thickness percentage (below 20%) was noted for breeding lines 11257-19, LAG24 and cultivar 'Zeus' (17.87%, 18.91% 19.60%, respectively). Despite having low seed weight, the Australian line no. 11257-19 was characterized by a desirable proportion of seed coat to the weight of seeds. In general, estimation of the correlation coefficient indicated a tendency that larger seeds had thinner coats. Scanning Electron Microscopy images showed low variation of seed coat sculpture and the top of seeds covered with a cuticle. Most of the studied genotypes were characterized by a cristatepapillate seed coat surface, formed by elongated polygonal cells. Only breeding line no. 11267-19 had a different shape of the cells building the surface layer of the coat. In order to illustrate genetic diversity among the genotypes tested, 24 ISSR primers were used. They generated a total of 161 polymorphic amplification products in 10 evaluated narrow-leaved lupin genotypes. PMID- 25119984 TI - Differential responses of herbivores and herbivory to management in temperate European beech. AB - Forest management not only affects biodiversity but also might alter ecosystem processes mediated by the organisms, i.e. herbivory the removal of plant biomass by plant-eating insects and other arthropod groups. Aiming at revealing general relationships between forest management and herbivory we investigated aboveground arthropod herbivory in 105 plots dominated by European beech in three different regions in Germany in the sun-exposed canopy of mature beech trees and on beech saplings in the understorey. We separately assessed damage by different guilds of herbivores, i.e. chewing, sucking and scraping herbivores, gall-forming insects and mites, and leaf-mining insects. We asked whether herbivory differs among different forest management regimes (unmanaged, uneven-aged managed, even-aged managed) and among age-classes within even-aged forests. We further tested for consistency of relationships between regions, strata and herbivore guilds. On average, almost 80% of beech leaves showed herbivory damage, and about 6% of leaf area was consumed. Chewing damage was most common, whereas leaf sucking and scraping damage were very rare. Damage was generally greater in the canopy than in the understorey, in particular for chewing and scraping damage, and the occurrence of mines. There was little difference in herbivory among differently managed forests and the effects of management on damage differed among regions, strata and damage types. Covariates such as wood volume, tree density and plant diversity weakly influenced herbivory, and effects differed between herbivory types. We conclude that despite of the relatively low number of species attacking beech; arthropod herbivory on beech is generally high. We further conclude that responses of herbivory to forest management are multifaceted and environmental factors such as forest structure variables affecting in particular microclimatic conditions are more likely to explain the variability in herbivory among beech forest plots. PMID- 25119985 TI - Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine structural analogs. AB - Taurine activates and modulates GABA receptors in vivo as well as those expressed in heterologous systems. This study aimed to determine whether the structural analogs of taurine: homotaurine and hypotaurine, have the ability to activate GABA-A receptors that include GABArho subunits. The expression of GABA-A receptors containing GABArho has been reported in the STC-1 cells and astrocytes. In both cell types, taurine, homo-, and hypotaurine gated with low efficiency a picrotoxin-sensitive GABA-A receptor. The known bimodal modulatory effect of taurine on GABArho receptors was not observed; however, differences between the activation and deactivation rates were detected when they were perfused together with GABA. In silico docking simulations suggested that taurine, hypo-, and homotaurine do not form a cation-pi interaction such as that generated by GABA in the agonist-binding site of GABArho. This observation complements the electrophysiological data suggesting that taurine and its analogs act as partial agonists of GABA-A receptors. All the observations above suggest that the structural analogs of taurine are partial agonists of GABA-A receptors that occupy the agonist-binding site, but their structures do not allow the proper interaction with the receptor to fully gate its Cl(-) channel. PMID- 25119986 TI - Adjuvant chemotherapy after radical cystectomy for bladder cancer: a comparative study using inverse-probability-of-treatment weighting. AB - OBJECTIVES: The role of adjuvant chemotherapy (AC) after radical cystectomy for bladder cancer remains unclear. This study evaluated the benefits of cisplatin based AC plus surgery versus surgery alone in patients with bladder cancer. MATERIALS AND METHODS: The medical records of 746 patients who underwent radical cystectomy for bladder cancer were reviewed. The association between AC and survival was analyzed using Cox regression models. To reduce the impact of treatment selection bias and potential confounding in an observational study, significant differences in patient characteristics were rigorously adjusted using inverse-probability-of-treatment weighting (IPTW). RESULTS: The cohort consisted of 746 patients (664 men and 82 women) of mean age 62.4 years and median follow up of 64.3 months (range, 1-231.4 months). Of these patients, 176 (23.6%) received AC after cystectomy and 570 (76.4%) underwent cystectomy alone. Patients who received AC were significantly younger (60 vs. 63 years, p = 0.001) and significantly more likely to have high pathologic T stage (p = 0.001), lymph node metastasis (p = 0.001), high grade (p = 0.001), and lymphovascular invasion (p = 0.001) than patients who underwent cystectomy alone. Multivariable analysis showed a cancer-specific survival (CSS) benefit for AC [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.39-0.80, p = 0.002], as did low pathologic T stage, absence of lymph node metastasis, and absence of lymphovascular invasion. After IPTW adjustment for baseline characteristics, AC remained an independent predictor of CSS (HR 0.83, 95% CI 0.69-0.99, p = 0.043). CONCLUSIONS: Cisplatin based AC after radical cystectomy had survival benefits in patients with bladder cancer, even after IPTW adjustment for confounding variables. PMID- 25119987 TI - Severe gastrointestinal bleeding in patients with locally advanced head and neck squamous cell carcinoma treated by concurrent radiotherapy and Cetuximab. AB - PURPOSE: Concurrent administration of Cetuximab with radiotherapy (Cetuximab radiation) has been accepted as an alternative option for locally advanced head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to retrospectively compare complications of Cetuximab-radiation with those of concurrent chemoradiation (cCRT) with a special concern on gastrointestinal (GI) hemorrhage associated with Cetuximab-radiation. METHODS: Indication of Cetuximab radiation/cCRT for locally advanced HNSCC was primary, postoperative adjuvant, or salvage after recurrence. Our first choice for patients with advanced HNSCC was cCRT; however, if patients did not have enough organ function but with a favorable performance status, Cetuximab-radiation was applied. RESULTS: From April 2013 to March 2014, 30 patients were identified who were treated with Cetuximab-radiation or cCRT and each cohort consisted of 15 patients. Patients in Cetuximab-radiation cohort suffered from a statistically higher rate of G3/4 dermatitis compared with cCRT cohort (80 vs. 13.3%, respectively, p < 0.001). More patients required unexpected hospitalization due to deterioration of their general condition and total parenteral nutrition in Cetuximab-radiation cohort (p = 0.011 and p = 0.025, respectively). While none experienced GI bleeding in cCRT cohort, four patients experienced GI bleeding including two grade 4 bleeding in Cetuximab-radiation cohort (p = 0.05). CONCLUSIONS: It is probable that there exists a group of patients who are susceptible for Cetuximab-radiation not only in terms of well-known dermatitis and mucositis but also of gastrointestinal complications. PMID- 25119988 TI - Genome analysis of Bacillus amyloliquefaciens Subsp. plantarum UCMB5113: a rhizobacterium that improves plant growth and stress management. AB - The Bacillus amyloliquefaciens subsp. plantarum strain UCMB5113 is a Gram positive rhizobacterium that can colonize plant roots and stimulate plant growth and defense based on unknown mechanisms. This reinforcement of plants may provide protection to various forms of biotic and abiotic stress. To determine the genetic traits involved in the mechanism of plant-bacteria association, the genome sequence of UCMB5113 was obtained by assembling paired-end Illumina reads. The assembled chromosome of 3,889,532 bp was predicted to encode 3,656 proteins. Genes that potentially contribute to plant growth promotion such as indole-3 acetic acid (IAA) biosynthesis, acetoin synthesis and siderophore production were identified. Moreover, annotation identified putative genes responsible for non ribosomal synthesis of secondary metabolites and genes supporting environment fitness of UCMB5113 including drug and metal resistance. A large number of genes encoding a diverse set of secretory proteins, enzymes of primary and secondary metabolism and carbohydrate active enzymes were found which reflect a high capacity to degrade various rhizosphere macromolecules. Additionally, many predicted membrane transporters provides the bacterium with efficient uptake capabilities of several nutrients. Although, UCMB5113 has the possibility to produce antibiotics and biosurfactants, the protective effect of plants to pathogens seems to be indirect and due to priming of plant induced systemic resistance. The availability of the genome enables identification of genes and their function underpinning beneficial interactions of UCMB5113 with plants. PMID- 25119989 TI - Cyclophilin A (CypA) interacts with NF-kappaB subunit, p65/RelA, and contributes to NF-kappaB activation signaling. AB - BACKGROUND: Peptidyl-prolyl isomerase cyclophilin A (CypA) plays important roles in signaling, protein translocation, inflammation, and cancer formation. However, little is known about the mechanisms by which CypA exerts its effects. C57BL/6 Ppia (encoding CypA)-deficient embryonic fibroblasts show reduced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), the p65/RelA subunit, suggesting that CypA may mediate modulation of NF-kappaB activity to exert its biological effects. METHODOLOGY: Western blotting and qRT PCR analyses were used to evaluate the association of CypA deficiency with reduced activation of NF-kappaB/p65 at the protein level. GST pull-down and co immunoprecipitation were used to examine interactions between CypA and p65/RelA. Truncation mutants and site-directed mutagenesis were used to determine the sequences of p65/RelA required for interactions with CypA. Enhancement of p65/RelA nuclear translocation by CypA was assessed by co-transfection and immunofluorescent imaging. Treatment of cells with cycloheximide that were harvested at various time points for Western blot analyses was carried out to evaluate p65/RelA protein stability. The functional activity of NF-kappaB was assessed by electrophoretic mobility-shift assays (EMSA), luciferase assays, and changes in expression levels of target genes. RESULTS: GST pull-down assays in vitro and co-immunoprecipitation analyses in vivo provided evidence for protein protein interactions. These interactions were further supported by identification of a CypA-binding consensus-like sequence within NF-kappaB subunit p65 at the N terminal 170-176 amino acid residues. Significantly, CypA provided stability for NF-kappaB p65 and promoted NF-kappaB p65 nuclear translocation, resulting in increased nuclear accumulation and enhanced NF-kappaB activity. CONCLUSIONS: Our findings revealed important mechanisms that regulate NF-kappaB activation, and offer new insights into the role of CypA in aberrant activation of NF-kappaB mediated signaling for altered expression of its target genes, resulting in pathological effects in various diseases. PMID- 25119991 TI - Comparative analysis of seven viral nuclear export signals (NESs) reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP) in influenza A virus replication. AB - The assembly of influenza virus progeny virions requires machinery that exports viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear export signal (NES) consensus sequences have been identified in different viral proteins, including NS1, NS2, M1, and NP. The present study examined the roles of viral NES consensus sequences and their significance in terms of viral replication and nuclear export. Mutation of the NP-NES3 consensus sequence resulted in a failure to rescue viruses using a reverse genetics approach, whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction in viral replication kinetics compared with the wild-type sequence. While the viral replication kinetics for other NES mutant viruses were also lower than those of the wild-type, the difference was not so marked. Immunofluorescence analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in host cells showed that they accumulated in the cell nucleus. These results suggest that the NP-NES3 consensus sequence is mostly required for viral replication. Therefore, each of the hydrophobic (Phi) residues within this NES consensus sequence (Phi1, Phi2, Phi3, or Phi4) was mutated, and its viral replication and nuclear export function were analyzed. No viruses harboring NP NES3 Phi2 or Phi3 mutants could be rescued. Consistent with this, the NP-NES3 Phi2 and Phi3 mutants showed reduced binding affinity with CRM1 in a pull-down assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay revealed that these mutant proteins showed lower nuclear export activity than the wild-type protein. Moreover, the Phi2 and Phi3 residues (along with other Phi residues) within the NP-NES3 consensus were highly conserved among different influenza A viruses, including human, avian, and swine. Taken together, these results suggest that the Phi2 and Phi3 residues within the NP-NES3 protein are important for its nuclear export function during viral replication. PMID- 25119992 TI - Kinetic analysis of the multistep aggregation mechanism of monoclonal antibodies. AB - We investigate by kinetic analysis the aggregation mechanism of two monoclonal antibodies belonging to the IgG1 and IgG2 subclass under thermal stress. For each IgG, we apply a combination of size exclusion chromatography and light scattering techniques to resolve the time evolution of the monomer, dimer, and trimer concentrations, as well as the average molecular weight and the average hydrodynamic radius of the aggregate distribution. By combining the detailed experimental characterization with a theoretical kinetic model based on population balance equations, we extract relevant information on the contribution of the individual elementary steps on the global aggregation process. The analysis shows that the two molecules follow different aggregation pathways under the same operating conditions. In particular, while the monomer depletion of the IgG1 is found to be rate-limited by monomeric conformational changes, bimolecular collision is identified as the rate-limiting step in the IgG2 aggregation process. The measurement of the microscopic rate constants by kinetic analysis allows the quantification of the protein-protein interaction potentials expressed in terms of the Fuchs stability ratio (W). It is found that the antibody solutions exhibit large W values, which are several orders of magnitude larger than the values computed in the frame of the DLVO theory. This indicates that, besides net electrostatic repulsion, additional effects delay the aggregation kinetics of the antibody solutions with respect to diffusion-limited conditions. These effects likely include the limited efficiency of the collision events due to the presence of a limited number of specific aggregation-prone patches on the heterogeneous protein surface, and the contribution of additional repulsive non DLVO forces to the protein-protein interaction potential, such as hydration forces. PMID- 25119993 TI - Isoegomaketone induces apoptosis in SK-MEL-2 human melanoma cells through mitochondrial apoptotic pathway via activating the PI3K/Akt pathway. AB - Isoegomaketone (IK) is a major biologically active component of Perilla frutescens. In this study, we investigated the contribution of reactive oxygen species (ROS) to IK-induced apoptosis in human melanoma SK-MEL-2 cells. We found that IK inhibited the proliferation of SK-MEL-2 human melanoma cells in a dose dependent manner. IK also induced sub-G1 DNA accumulation, formation of apoptotic bodies, nuclear condensation, and a DNA ladder in SK-MEL-2 cells. IK also induced activation of caspase-3 and -9, whereas caspase-8 was unaffected. Further, N acetyl-L-cysteine (NAC, ROS scavenger) treatment to SK-MEL-2 cells significantly reduced IK-induced cell death. Pretreatment of NAC to SK-MEL-2 cells followed by 100 uM IK reduced the protein levels of Bax and cytochrome c as well as PARP cleavage, whereas the protein level of Bcl-2 increased. Moreover, IK inhibited the phosphorylation of AKT/mTOR protein and cell proliferation induced by LY294002, a PI3K inhibitor. In conclusion, IK-induced ROS generation regulates cell growth inhibition and it induces apoptosis through caspase-dependent and independent pathways via modulation of PI3K/AKT signaling in SK-MEL-2 cells. PMID- 25119994 TI - Preparation and in vitro/in vivo characterization of tranilast-AMP clay complex for improving drug dissolution and bioavailability. AB - The present study aimed to develop an effective oral formulation of tranilast (TL), a poorly soluble anti-inflammatory drug, via the formation of drug complex with 3-aminopropyl functionalized magnesium phyllosilicate (AMP clay) and improve the pH-dependent drug dissolution and bioavailability of TL. The drug-clay complex (TL-AMP complex) was prepared by co-precipitation method and its structural properties were characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy and transmission electron microscopy. The dissolution profiles of TL-AMP complex were evaluated at different pHs. The formation of TL-AMP complex significantly improved the dissolution rate as well as the extent of drug release at acidic pHs, while the dissolution of untreated TL was negligible at pH 1.2 and 4.0. TL-AMP complex also achieved faster drug release than untreated drug (about 90 vs 30 % within 30 min) at pH 6.8. After oral administration to rats, TL-AMP complex enhanced significantly (p < 0.05) oral drug exposure and increased Cmax and AUC by six- and threefolds, respectively, compared to untreated TL. In conclusion, TL-AMP complex may be promising to improve the pH-dependent dissolution as well as bioavailability of TL. PMID- 25119995 TI - Identification of significant features by the Global Mean Rank test. AB - With the introduction of omics-technologies such as transcriptomics and proteomics, numerous methods for the reliable identification of significantly regulated features (genes, proteins, etc.) have been developed. Experimental practice requires these tests to successfully deal with conditions such as small numbers of replicates, missing values, non-normally distributed expression levels, and non-identical distributions of features. With the MeanRank test we aimed at developing a test that performs robustly under these conditions, while favorably scaling with the number of replicates. The test proposed here is a global one-sample location test, which is based on the mean ranks across replicates, and internally estimates and controls the false discovery rate. Furthermore, missing data is accounted for without the need of imputation. In extensive simulations comparing MeanRank to other frequently used methods, we found that it performs well with small and large numbers of replicates, feature dependent variance between replicates, and variable regulation across features on simulation data and a recent two-color microarray spike-in dataset. The tests were then used to identify significant changes in the phosphoproteomes of cancer cells induced by the kinase inhibitors erlotinib and 3-MB-PP1 in two independently published mass spectrometry-based studies. MeanRank outperformed the other global rank-based methods applied in this study. Compared to the popular Significance Analysis of Microarrays and Linear Models for Microarray methods, MeanRank performed similar or better. Furthermore, MeanRank exhibits more consistent behavior regarding the degree of regulation and is robust against the choice of preprocessing methods. MeanRank does not require any imputation of missing values, is easy to understand, and yields results that are easy to interpret. The software implementing the algorithm is freely available for academic and commercial use. PMID- 25119996 TI - Rising CO2 levels will intensify phytoplankton blooms in eutrophic and hypertrophic lakes. AB - Harmful algal blooms threaten the water quality of many eutrophic and hypertrophic lakes and cause severe ecological and economic damage worldwide. Dense blooms often deplete the dissolved CO2 concentration and raise pH. Yet, quantitative prediction of the feedbacks between phytoplankton growth, CO2 drawdown and the inorganic carbon chemistry of aquatic ecosystems has received surprisingly little attention. Here, we develop a mathematical model to predict dynamic changes in dissolved inorganic carbon (DIC), pH and alkalinity during phytoplankton bloom development. We tested the model in chemostat experiments with the freshwater cyanobacterium Microcystis aeruginosa at different CO2 levels. The experiments showed that dense blooms sequestered large amounts of atmospheric CO2, not only by their own biomass production but also by inducing a high pH and alkalinity that enhanced the capacity for DIC storage in the system. We used the model to explore how phytoplankton blooms of eutrophic waters will respond to rising CO2 levels. The model predicts that (1) dense phytoplankton blooms in low- and moderately alkaline waters can deplete the dissolved CO2 concentration to limiting levels and raise the pH over a relatively wide range of atmospheric CO2 conditions, (2) rising atmospheric CO2 levels will enhance phytoplankton blooms in low- and moderately alkaline waters with high nutrient loads, and (3) above some threshold, rising atmospheric CO2 will alleviate phytoplankton blooms from carbon limitation, resulting in less intense CO2 depletion and a lesser increase in pH. Sensitivity analysis indicated that the model predictions were qualitatively robust. Quantitatively, the predictions were sensitive to variation in lake depth, DIC input and CO2 gas transfer across the air-water interface, but relatively robust to variation in the carbon uptake mechanisms of phytoplankton. In total, these findings warn that rising CO2 levels may result in a marked intensification of phytoplankton blooms in eutrophic and hypertrophic waters. PMID- 25119997 TI - Hemispheric asymmetry in the auditory facilitation effect in dual-stream rapid serial visual presentation tasks. AB - Even though auditory stimuli do not directly convey information related to visual stimuli, they often improve visual detection and identification performance. Auditory stimuli often alter visual perception depending on the reliability of the sensory input, with visual and auditory information reciprocally compensating for ambiguity in the other sensory domain. Perceptual processing is characterized by hemispheric asymmetry. While the left hemisphere is more involved in linguistic processing, the right hemisphere dominates spatial processing. In this context, we hypothesized that an auditory facilitation effect in the right visual field for the target identification task, and a similar effect would be observed in the left visual field for the target localization task. In the present study, we conducted target identification and localization tasks using a dual-stream rapid serial visual presentation. When two targets are embedded in a rapid serial visual presentation stream, the target detection or discrimination performance for the second target is generally lower than for the first target; this deficit is well known as attentional blink. Our results indicate that auditory stimuli improved target identification performance for the second target within the stream when visual stimuli were presented in the right, but not the left visual field. In contrast, auditory stimuli improved second target localization performance when visual stimuli were presented in the left visual field. An auditory facilitation effect was observed in perceptual processing, depending on the hemispheric specialization. Our results demonstrate a dissociation between the lateral visual hemifield in which a stimulus is projected and the kind of visual judgment that may benefit from the presentation of an auditory cue. PMID- 25119998 TI - The 5 kDa protein NdhP is essential for stable NDH-1L assembly in Thermosynechococcus elongatus. AB - The cyanobacterial NADPH:plastoquinone oxidoreductase complex (NDH-1), that is related to Complex I of eubacteria and mitochondria, plays a pivotal role in respiration as well as in cyclic electron transfer (CET) around PSI and is involved in a unique carbon concentration mechanism (CCM). Despite many achievements in the past, the complex protein composition and the specific function of many subunits of the different NDH-1 species remain elusive. We have recently discovered in a NDH-1 preparation from Thermosynechococcus elongatus two novel single transmembrane peptides (NdhP, NdhQ) with molecular weights below 5 kDa. Here we show that NdhP is a unique component of the ~ 450 kDa NDH-1L complex, that is involved in respiration and CET at high CO2 concentration, and not detectable in the NDH-1MS and NDH-1MS' complexes that play a role in carbon concentration. C-terminal fusion of NdhP with his-tagged superfolder GFP and the subsequent analysis of the purified complex by electron microscopy and single particle averaging revealed its localization in the NDH-1L specific distal unit of the NDH-1 complex, that is formed by the subunits NdhD1 and NdhF1. Moreover, NdhP is essential for NDH-1L formation, as this type of NDH-1 was not detectable in a DeltandhP::Km mutant. PMID- 25119999 TI - Modelling size structured food webs using a modified niche model with two predator traits. AB - The structure of food webs is frequently described using phenomenological stochastic models. A prominent example, the niche model, was found to produce artificial food webs resembling real food webs according to a range of summary statistics. However, the size structure of food webs generated by the niche model and real food webs has not yet been rigorously compared. To fill this void, I use a body mass based version of the niche model and compare prey-predator body mass allometry and predator-prey body mass ratios predicted by the model to empirical data. The results show that the model predicts weaker size structure than observed in many real food webs. I introduce a modified version of the niche model which allows to control the strength of size-dependence of predator-prey links. In this model, optimal prey body mass depends allometrically on predator body mass and on a second trait, such as foraging mode. These empirically motivated extensions of the model allow to represent size structure of real food webs realistically and can be used to generate artificial food webs varying in several aspects of size structure in a controlled way. Hence, by explicitly including the role of species traits, this model provides new opportunities for simulating the consequences of size structure for food web dynamics and stability. PMID- 25120000 TI - RNAseq analysis of cassava reveals similar plant responses upon infection with pathogenic and non-pathogenic strains of Xanthomonas axonopodis pv. manihotis. AB - KEY MESSAGE: An RNAseq-based analysis of the cassava plants inoculated with Xam allowed the identification of transcriptional upregulation of genes involved in jasmonate metabolism, phenylpropanoid biosynthesis and putative targets for a TALE. Cassava bacterial blight, a disease caused by the gram-negative bacterium Xanthomonas axonopodis pv. manihotis (Xam), is a major limitation to cassava production worldwide and especially in developing countries. The molecular mechanisms underlying cassava susceptibility to Xam are currently unknown. To identify host genes and pathways leading to plant susceptibility, we analyzed the transcriptomic responses occurring in cassava plants challenged with either the non-pathogenic Xam strain ORST4, or strain ORST4(TALE1 Xam ) which is pathogenic due to the major virulence transcription activator like effector TALE1 Xam . Both strains triggered similar responses, i.e., induction of genes related to photosynthesis and phenylpropanoid biosynthesis, and repression of genes related to jasmonic acid signaling. Finally, to search for TALE1 Xam virulence targets, we scanned the list of cassava genes induced upon inoculation of ORST4(TALE1 Xam ) for candidates harboring a predicted TALE1 Xam effector binding element in their promoter. Among the six genes identified as potential candidate targets of TALE1 Xam a gene coding for a heat shock transcription factor stands out as the best candidate based on their induction in presence of TALE1 Xam and contain a sequence putatively recognized by TALE1 Xam . PMID- 25120002 TI - Epidermal stem cells in the isthmus/infundibulum influence hair shaft differentiation: evidence from targeted DLX3 deletion. PMID- 25120001 TI - Knockdown of the 7S globulin subunits shifts distribution of nitrogen sources to the residual protein fraction in transgenic soybean seeds. AB - KEY MESSAGE: A platform of gene silencing by amiRNA had been established in fertile transgenic soybean. We demonstrated that knockdown of storage protein shifted the distribution of nitrogen sources in soybean seeds. Artificial microRNAs (amiRNAs) were designed using the precursor sequence of the endogenous soybean (Glycine max L. Merrill) miRNA gma-miR159a and expressed in transgenic soybean plants to suppress the biosynthesis of 7S globulin, which is one of the major storage proteins. Seed-specific expression of these amiRNAs (amiR-7S) resulted in a strong suppression of 7S globulin subunit genes and decreased accumulation of the 7S globulin subunits in seeds. Thus, the results demonstrate that a platform for gene silencing by amiRNA was first developed in fertile transgenic soybean plants. There was no difference in nitrogen, carbon, and lipid contents between amiR-7S and control seeds. Four protein fractions were collected from defatted mature seeds on the basis of solubility at different pH to examine the distribution of nitrogen sources and compensatory effects. In the whey and lipophilic fractions, nitrogen content was similar in amiR-7S and control seeds. Nitrogen content was significantly decreased in the major soluble protein fraction and increased in the residual fraction (okara) of the amiR-7S seeds. Amino acid analysis revealed that increased nitrogen compounds in okara were proteins or peptides rather than free amino acids. Our study indicates that the decrease in 7S globulin subunits shifts the distribution of nitrogen sources to okara in transgenic soybean seeds. PMID- 25120005 TI - Immunogenicity of biotherapy used in psoriasis: the science behind the scenes. AB - A potential limitation in the use of biologic drugs used to treat psoriasis is the development of anti-drug antibodies (ADAs). Many factors contribute to this unwanted immune response, from the product itself, to its mode of administration, the underlying disease, and patient characteristics. ADAs may decrease the efficacy of biologic drugs by neutralizing them or modifying their clearance and may account for hypersensitivity reactions. This article reviews the scientific basis of immunogenicity and the mechanisms by which it affects clinical outcomes. It also considers testing for immunogenicity and how biologic therapy of psoriasis may be tailored on the basis of immunogenicity. PMID- 25120007 TI - Biophysical characterisation of calumenin as a charged F508del-CFTR folding modulator. AB - The cystic fibrosis transmembrane regulator (CFTR) is a cyclic-AMP dependent chloride channel expressed at the apical surface of epithelial cells lining various organs such as the respiratory tract. Defective processing and functioning of this protein caused by mutations in the CFTR gene results in loss of ionic balance, defective mucus clearance, increased proliferation of biofilms and inflammation of human airways observed in cystic fibrosis (CF) patients. The process by which CFTR folds and matures under the influence of various chaperones in the secretory pathway remains incompletely understood. Recently, calumenin, a secretory protein, belonging to the CREC family of low affinity calcium binding proteins has been identified as a putative CFTR chaperone whose biophysical properties and functions remain uncharacterized. We compared hydropathy, instability, charge, unfoldability, disorder and aggregation propensity of calumenin and other CREC family members with CFTR associated chaperones and calcium binding proteins, wild-type and mutant CFTR proteins and intrinsically disordered proteins (IDPs). We observed that calumenin, along with other CREC proteins, was significantly more charged and less folded compared to CFTR associated chaperones. Moreover like IDPs, calumenin and other CREC proteins were found to be less hydrophobic and aggregation prone. Phylogenetic analysis revealed a close link between calumenin and other CREC proteins indicating how evolution might have shaped their similar biophysical properties. Experimentally, calumenin was observed to significantly reduce F508del-CFTR aggregation in a manner similar to AavLEA1, a well-characterized IDP. Fluorescence microscopy based imaging analysis also revealed altered trafficking of calumenin in bronchial cells expressing F508del-CFTR, indicating its direct role in the pathophysiology of CF. In conclusion, calumenin is characterized as a charged protein exhibiting close similarity with IDPs and is hypothesized to regulate F508del-CFTR folding by electrostatic effects. This work provides useful insights for designing optimized synthetic structural correctors of CFTR mutant proteins in the future. PMID- 25120009 TI - Baseline patient characteristics, incidence of CINV, and physician perception of CINV incidence following moderately and highly emetogenic chemotherapy in Asia Pacific countries. AB - PURPOSE: This paper describes the incidence of chemotherapy-induced nausea and vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. METHODS: Sequential adult patients naive to chemotherapy and scheduled to receive at least two cycles of single-day HEC or MEC were enrolled in this prospective observational study. Patients completed the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool on post-chemotherapy days 2 and 6 to record acute-phase (first 24 h) and delayed-phase (days 2-5) CINV. RESULTS: There were 648 evaluable patients (318 HEC, 330 MEC) from Australia (n = 74), China (153), India (88), Singapore (57), South Korea (151), and Taiwan (125). Mean (SD) patient age was 56 (12) and 58% of patients were women; the most common primary cancers were breast (27%), lung (22%), and colon (20%). Overall in cycle 1, complete response (no emesis or rescue antiemetics) was recorded by 69% (95% confidence interval (CI), 66-73) of all evaluable patients, with country percentages ranging from 55 to 78% (p < 0.001). After HEC, no emesis was recorded by 75% and no nausea by 38% of patients. After MEC, 80% had no emesis and 50% no nausea. Acute-phase CINV was better controlled than delayed-phase CINV, and the control of nausea was the lowest of any CINV measure in all phases. In a CINV perception survey, physicians tended to overestimate emesis rate and underestimate nausea rate. CONCLUSIONS: CINV remains a substantial problem, and country-specific information about CINV can be useful in developing strategies to improve outcomes for patients undergoing chemotherapy. PMID- 25120008 TI - Research in cancer care disparities in countries with universal healthcare: mapping the field and its conceptual contours. AB - The paper reviews published studies focused on disparities in receipt of cancer treatments and supportive care services in countries where cancer care is free at the point of access. We map these studies in terms of the equity stratifiers they examined, the countries in which they took place, and the care settings and cancer populations they investigated. Based on this map, we reflect on patterns of scholarly attention to equity and disparity in cancer care. We then consider conceptual challenges and opportunities in the field, including how treatment disparities are defined, how equity stratifiers are defined and conceptualized and how disparities are explained, with special attention to the challenge of psychosocial explanations. PMID- 25120010 TI - Distress among caregivers of phase I trial participants: a cross-sectional study. AB - PURPOSE: The number of patients with cancer enrolling in phase I trials is expected to increase as these trials incorporate patient selection and exhibit greater efficacy in the era of targeted therapies. Despite the fact that people with advanced cancer often require a caregiver, little is known about the experience of caregivers of people enrolling in oncology phase I clinical trials. We conducted a cross-sectional study assessing the distress and emotion regulation of caregivers of phase I trial participants to inform the design of future interventions targeting the unique needs of this population. METHODS: Caregivers of oncology patients were approached at the patient's phase I clinical trial screening visit. Caregiver participants completed a one-time survey incorporating validated instruments to comprehensively assess distress and emotion regulation. Basic demographic information about both the caregiver and patient was collected. RESULTS: Caregivers exhibited greater distress than population norms. Emotion regulation was also moderately impaired. Respondents identified positive aspects of caregiving despite exhibiting moderate distress. CONCLUSION: Enrollment of a patient in a phase I clinical trial is a time of stress for their caregivers. This pilot study demonstrates the feasibility of engaging caregivers of phase I trial participants and the need to better support them through this component of their caregiving experience. PMID- 25120011 TI - Reproductive health and endocrine disruption in women with breast cancer: a pilot study. AB - PURPOSE: The purpose of this study was to assess whether incorporation of an original reproductive health assessment and algorithm into breast cancer care helps providers appropriately manage patient reproductive health goals and to follow laboratory markers for fertility and correlate these with menstruation. METHODS: This prospective observational pilot study was set in an urban, public hospital. Newly diagnosed premenopausal breast cancer patients between 18 and 49 years old were recruited for this study prior to chemotherapy initiation. As the intervention, these patients received a reproductive health assessment and care per the study algorithm at 3-month intervals for 24 months. Blood samples were also collected at the same time intervals. The main outcome measures were to assess if the reproductive health management was consistent with patient goals and to track any follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) level changes throughout treatment and post-treatment period. RESULTS: Two patients were pregnant at study initiation. They received obstetric consultations, opted to continue pregnancies, and postpone treatment; both delivered at term without complications. One woman desired future childbearing and received fertility preservation counseling. All women received family planning consultations and received/continued effective contraceptive methods. Seventy-three percent used long-term contraception, 18 % remained abstinent, and 9 % used condoms. During chemotherapy, FSH rose to menopausal levels in 82 % of patients and TSH rose significantly in 9 %. While 82 % of women experienced amenorrhea, 44 % of these women resumed menstruation after chemotherapy. CONCLUSIONS: The assessment and algorithm were useful in managing patients' reproductive health needs. Chemotherapy-induced endocrine disruption impacted reproductive health. PMID- 25120012 TI - Peripherally inserted central catheters in non-hospitalized cancer patients: 5 year results of a prospective study. AB - PURPOSE: Few prospective follow-up studies evaluating the use of peripherally inserted central catheters (PICCs) to deliver chemotherapy and/or home parenteral nutrition (HPN) have focused exclusively on oncology outpatients. The aim of this prospective study was to assess the reliability and the safety of PICCs over a 5 year use in non-hospitalized cancer patients requiring long-term intravenous therapies. METHODS: Since June 2008, all adult oncology outpatient candidates for PICC insertion were consecutively enrolled and the incidence of catheter-related complications was investigated. The follow-up continued until the PICC removal. RESULTS: Two hundred sixty-nine PICCs in 250 patients (98 % with solid malignancies) were studied, for a total of 55,293 catheter days (median dwell time 184 days, range 15-1,384). All patients received HPN and 71 % received chemotherapy during the study period. The incidence of catheter-related bloodstream infections (CRBSIs) was low (0.05 per 1,000 catheter days), PICC related symptomatic thrombosis was rare (1.1 %; 0.05 per 1,000 catheter days), and mechanical complications were uncommon (13.1 %; 0.63 per 1,000 catheter days). The overall complication rate was 17.5 % (0.85 per 1,000 catheter days) and PICCs were removed because of complications only in 7 % of cases. The main findings of this study were that, if accurately managed, PICCs can be safely used in cancer patients receiving chemotherapy and/or HPN, recording a low incidence of CRBSI, thrombosis, and mechanical complications; a long catheter life span; and a low probability of catheter removal because of complications. CONCLUSIONS: Our study suggests that PICCs can be successfully utilized as safe and long lasting venous access devices in non-hospitalized cancer patients. PMID- 25120013 TI - Is there coronary artery disease in the cancer patient who manifests with chest pain, shortness of breath and/or tachycardia? A retrospective observational cohort. AB - OBJECTIVE: Cancer therapies lead to chest pain (CP), shortness of breath (SOB), and/or tachydysrhythmias (TACH Y) requiring cardiac risk stratification including coronary computed tomographic angiography (CCTA). We posit that cancer patients with CP, SOB and/or TACH Y have greater odds of having coronary artery disease (CAD) identified by CCTA than those that do not. METHODS: Eligibility for this IRB-approved retrospective observational cohort included those with cancer that had CCTA performed. Groups were stratified with and without CP, SOB, and/or TACH Y. Electronic medical records were mined for appropriate CPT codes from 01012010 to 08312013. Demographics, cancer type, and clinical outcomes were obtained. Standard t tests, odds ratios, and frequencies were used. RESULTS: Of 176 participants identified; 84 were male (48 %) and 118 were Caucasian (67 %). Of those, 100/176 (57 %) had CP, SOB, and/or TACH Y; 72/100 (72 %) had CP; 10/100 (10 %) had TACH Y; and 18/100 (18 %) had SOB. Of the 72 with CP, 40 (56 %) had CAD; of the 10 with TACH Y, 6 (60 %) had CAD; of the 18 with SOB, and 10 (56 %) had CAD. Thus, a 2.6-fold increased odds of having CAD (56/100 = 56 %) compared to 25/76 (33 %) in the group with cancer without CP, SOB, and/or TACH Y (95 % CI = 1.40 to 4.83; p = 0.003). CONCLUSION: Cancer patients with CP, SOB, and/or TACH Y have a 2.6-fold increased odds of having CAD compared to cancer patients without CP, SOB, and/or TACH Y (95 % CI = 1.40 to 4.83; p = 0.003). PMID- 25120015 TI - Antiplatelet therapy in the management of myeloproliferative neoplasms. AB - Low-dose acetylsalicylic acid (ASA) is given to most patients with polycythemia vera (PV) and essential thrombocythemia (ET) although some uncertainties encompass this clinical practice. In patients with history of thrombosis, the use of ASA is supported on the results observed in the general population showing a substantial net benefit of this treatment in preventing thrombosis. In the European collaboration study on low-dose aspirin in polycythemia vera (ECLAP), ASA reduced the risk of thrombosis without increasing the risk of major bleeding when compared with placebo, supporting the primary prevention of thrombosis in PV. In ET, the efficacy of low-dose ASA has not been tested in randomized clinical trials. Two retrospective studies have shown that low-dose ASA could benefit ET patients older than 60 years when combined with cytoreduction, whereas in young, low-risk patients, ASA benefits to particular subgroups of patients. In spite of the fact that in primary myelofibrosis the incidence of thrombosis is increased, the use of ASA is not clearly recommended. PMID- 25120014 TI - Exploring the relation of harsh parental discipline with child emotional and behavioral problems by using multiple informants. The generation R study. AB - Parental harsh disciplining, like corporal punishment, has consistently been associated with adverse mental health outcomes in children. It remains a challenge to accurately assess the consequences of harsh discipline, as researchers and clinicians generally rely on parent report of young children's problem behaviors. If parents rate their parenting styles and their child's behavior this may bias results. The use of child self-report on problem behaviors is not common but may provide extra information about the relation of harsh parental discipline and problem behavior. We examined the independent contribution of young children's self-report above parental report of emotional and behavioral problems in a study of maternal and paternal harsh discipline in a birth cohort. Maternal and paternal harsh discipline predicted both parent reported behavioral and parent reported emotional problems, but only child reported behavioral problems. Associations were not explained by pre-existing behavioral problems at age 3. Importantly, the association with child reported outcomes was independent from parent reported problem behavior. These results suggest that young children's self-reports of behavioral problems provide unique information on the effects of harsh parental discipline. Inclusion of child self reports can therefore help estimate the effects of harsh parental discipline more accurately. PMID- 25120018 TI - Size effects in bimagnetic CoO/CoFe2O4 core/shell nanoparticles. AB - The control of the size of bimagnetic nanoparticles represents an important step toward the study of fundamental properties and the design of new nanostructured magnetic materials. We report the synthesis and the structural and magnetic characterization of bimagnetic CoO/CoFe2O4 core/shell nanoparticles. The material was fabricated by a seed-mediated growth high-temperature decomposition method with sizes in the range of 5-11 nm. We show that the core/shell morphology favours the crystallinity of the shell phase, and the reduction of the particle size leads to a remarkable increase of the magnetic hardening. When the size is reduced, the coercive field at 5 K increases from 21.5 kOe to 30.8 kOe, while the blocking temperature decreases from 388 K to 167 K. The size effects on the magnetic behaviour are described through a phenomenological model for strongly ferri-/antiferromagnetic coupled phases. PMID- 25120016 TI - Functional and psychosocial impact of oral disorders and quality of life of people living with HIV/AIDS. AB - PURPOSE: This study compared the Quality of Life (QOL) according to the presence of functional and psychosocial impact of oral disorders and evaluated the convergent validity between the dimensions of the WHOQOL and the OHIP-14 scores among people living with HIV. METHODS: This was a cross-sectional study with patients enrolled in reference centres of a midsize Brazilian city. Interviews were conducted when the participants arrived at the centres seeking services for medical appointments and collecting medicines. The OHIP-14 was used to evaluate the functional and psychosocial impact of oral disorders. QOL was assessed using the general issues and six domains of the WHOQOL-HIV BREF. The Chi square test, Mann-Whitney test, and Spearman correlation analysis were used for analysis. RESULTS: The sample comprised 422 people living with HIV/AIDS (response rate: 81.2%). The prevalence of functional and psychosocial impact of oral disorders was 34.0%. The prevalence of very poor/poor QOL and those who were very dissatisfied/dissatisfied with their health was higher among those with functional and psychosocial impact of oral disorders. There was a negative correlation between the scores on the domains of QOL and the severity of the impact of the oral disorders (r-value ranged from -0.107 to -0.30). CONCLUSION: Individuals with functional and psychosocial impact of oral disorders were found to more frequently rate their QOL as poor/very poor, and were more often dissatisfied with health. The correlation between the scores of QOL and functional and psychosocial impact of oral disorders scores was weak, indicating that they represent different constructs. The measures of functional and psychosocial impact of oral disorders should be complemented by general measures of QOL. PMID- 25120019 TI - Fibroelastolytic papulosis in an elderly woman with a 30-year history: overlapping between pseudoxanthoma elasticum-like papillary dermal elastolysis and white fibrous papulosis of the neck. PMID- 25120017 TI - Quality of life after pulmonary embolism: first cross-cultural evaluation of the pulmonary embolism quality-of-life (PEmb-QoL) questionnaire in a Norwegian cohort. AB - PURPOSE: The aim of the current study was to translate and test the psychometrical properties of the disease-specific pulmonary embolism quality-of life questionnaire (PEmb-QoL). METHODS: Patients with a prior history of pulmonary embolism (PE) were identified from the thrombosis registry at Ostfold Hospital Trust, Fredrikstad, Norway. All eligible patients were asked to complete the generic EuroQol 5-dimension (EQ-5D) QoL questionnaire as well as the disease specific PEmb-QoL at baseline and after 2 weeks. Construct validity was tested using principal component factor analysis. Criterion validity was tested using Spearman's correlation coefficients (rho) between EQ-5D and PEmb-QoL. Internal consistency reliability was calculated using Cronbach's alpha coefficient, while test-retest reliability was calculated using the intra-class correlation coefficients (ICC). RESULTS: A total of 213 participants had complete datasets and were included in further analyses. Factor analysis with varimax rotation yielded six factors explaining 71% of the cumulative variance. Cronbach's alpha coefficient was found to be 0.94, indicating a very good intercorrelation of items. Of the 213 participants, 145 (68%) completed the questionnaire a second time. The ICC ranged from 0.75 to 0.86, indicating good test-retest reliability. All factors were found significant with p values <0.001. The criterion validity of the PEmb-QoL was confirmed through good correlation with other similar health related quality-of-life constructs in the EQ-5D. CONCLUSIONS: Findings of the current study indicate that Norwegian version of the PEmb-QoL is both valid and reliable, thus representing an important supplement in subjective outcomes measurement among patients sustaining PE. PMID- 25120021 TI - Cellular transplantation-based evolving treatment options in spinal cord injury. AB - Spinal cord injury (SCI) often represents a condition of permanent neurologic deficit. It has been possible to understand and delineate the mechanisms contributing to loss of function following primary injury. The clinicians might hope to improve the outcome in SCI injury by designing treatment strategies that could target these secondary mechanisms of response to injury. However, the approaches like molecular targeting of the neurons or surgical interventions have yielded very limited success till date. In recent times, a great thrust is put on to the cellular transplantation mode of treatment strategies to combat SCI problems so as to gain maximum functional recovery. In this review, we discuss about the various cellular transplantation strategies that could be employed in the treatment of SCI. The success of such cellular approaches involving Schwann cells, olfactory ensheathing cells, peripheral nerve, embryonic CNS tissue and activated macrophage has been supported by a number of reports and has been detailed here. Many of these cell transplantation strategies have reached the clinical trial stages. Also, the evolving field of stem cell therapy has made it possible to contemplate the role of both embryonic stem cells and induced pluripotent stem cells to stimulate the differentiation of neurons when transplanted in SCI models. Moreover, the roles of tissue engineering techniques and synthetic biomaterials have also been explained with their beneficial and deleterious effects. Many of these cell-based therapeutic approaches have been able to cause only a little change in recovery and a combinatorial approach involving more than one strategy are now being tried out to successfully treat SCI and improve functional recovery. PMID- 25120020 TI - Species distribution of clinical Acinetobacter isolates revealed by different identification techniques. AB - A total of 2582 non-duplicate clinical Acinetobacter spp. isolates were collected to evaluate the performance of four identification methods because it is important to identify Acinetobacter spp. accurately and survey the species distribution to determine the appropriate antimicrobial treatment. Phenotyping (VITEK 2 and VITEK MS) and genotyping (16S rRNA and rpoB gene sequencing) methods were applied for species identification, and antimicrobial susceptibility test of imipenem and meropenem was performed with a disk diffusion assay. Generally, the phenotypic identification results were quite different from the genotyping results, and their discrimination ability was unsatisfactory, whereas 16S rRNA and rpoB gene sequencing showed consistent typing results, with different resolution. Additionally, A. pittii, A. calcoaceticus and A. nosocomialis, which were phylogenetically close to A. baumannii, accounted for 85.5% of the non-A. baumannii isolates. One group, which could not be clustered with any reference strains, consisted of 11 isolates and constituted a novel Acinetobacter species that was entitled genomic species 33YU. None of the non-A. baumannii isolates harbored a blaOXA-51-like gene, and this gene was disrupted by ISAba19 in only one isolate; it continues to be appropriate as a genetic marker for A. baumannii identification. The resistance rate of non-A. baumannii isolates to imipenem and/or meropenem was only 2.6%, which was significantly lower than that of A. baumannii. Overall, rpoB gene sequencing was the most accurate identification method for Acinetobacter species. Except for A. baumannii, the most frequently isolated species from the nosocomial setting were A. pittii, A. calcoaceticus and A. nosocomialis. PMID- 25120022 TI - Dosage effect of rocuronium on intraoperative neuromonitoring in patients undergoing thyroid surgery. AB - The effect of different concentrations of rocuronium bromide used for anesthesia induction during thyroid surgery on the intraoperative recurrent laryngeal nerve monitoring was evaluated. One hundred patients undergoing thyroid operation were randomized into five groups (20 patients per group). Patients in group I were operated and monitored without the use of rocuronium bromide. Patients in groups II-V were respectively injected with 0.5x, 1x, 1.5x, and 2x ED95 rocuronium bromide intravenously. The time from injecting the rocuronium bromide to the beginning of tube insertion was recorded, the conditions of tracheal intubation were evaluated, and the changes in blood pressure and pulse during the intubation process were monitored. Vagus nerve/recurrent laryngeal nerve evoked muscle potential was monitored using the NIM-Response3.0 nerve electromyography monitor. The amplitude of electromyography signal was recorded every 5 min during 30 min after successful tracheal intubation. The tracheal intubation success rate was 100% in all groups. Compared with group I, intubating condition scores (Cooper scores) in the patients of groups II-V were higher (P < 0.05). The stability of intraoperative neuromonitoring signal amplitude in groups I-III met the monitoring standards. The findings suggest that the use of 0.5x or 1x ED95 rocuronium bromide during the anesthesia induction can improve the tracheal tube conditions without affecting the intraoperative recurrent laryngeal nerve monitoring. The use of 1x ED95 rocuronium bromide induction was associated with the best results. PMID- 25120023 TI - High-level S100A6 promotes metastasis and predicts the outcome of T1-T2 stage in clear cell renal cell carcinoma. AB - S100A6 (calcyclin), functions in cell cycle progression and differentiation, has been reported to promote the tumorigenesis and malignancy of many types of cancers. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC, lacking both promising prognostic markers and effective therapeutic targets. In our previous study, we have found the elevated S100A6 in the ccRCC tumor tissues, and the differentially expressed genes determined by microarray analysis were found to be strongly related to tumor metastasis after S100A6 knockdown and overexpression in the ccRCC cell line 786-O. The mRNA expression of S100A6 detected by RT-PCR in 6 cell lines and 174 tumor tissues, including 58 metastatic ccRCC and 116 clinicopathological features paired non-metastatic ccRCC (1:2), indicated S100A6 was elevated in the metastatic cells and tumor tissues. The protein expression was consistent with mRNA expression. The biological function of S100A6 in promoting metastasis was determined through overexpression and knockdown of S100A6 in the ccRCC cell lines 786-O, caki-1, and ACHN. In the scratch wound migration assay as well as migration and invasion assays, S100A6 knockdown significantly suppressed the migratory and invasive abilities of tumor cells, whereas overexpression enhanced the malignancy. Further research with the follow-up data of 129 ccRCC patients were analyzed by the Cox regression and survival analysis. The expression of S100A6 was up-regulated in metastatic ccRCC cells. In the metastatic tumor tissues, the expression of S100A6 was also higher than in the non-metastatic tissues. High S100A6 expression might be crucial to promote metastasis in ccRCC by enhancing the ability of tumor cells migration and invasion. In addition, the quantitative mRNA expression of S100A6 in the tumor tissues was an independent risk factor and might be used as a prognostic marker for the metastatic risk of the localized T1-T2 stage ccRCC. PMID- 25120025 TI - Effects of brain lesions on moral agency: ethical dilemmas in investigating moral behavior. AB - Understanding how the "brain produces behavior" is a guiding idea in neuroscience. It is thus of no surprise that establishing an interrelation between brain pathology and antisocial behavior has a long history in brain research. However, interrelating the brain with moral agency--the ability to act in reference to right and wrong--is tricky with respect to therapy and rehabilitation of patients affected by brain lesions. In this contribution, we outline the complexity of the relationship between the brain and moral behavior, and we discuss ethical issues of the neuroscience of ethics and of its clinical consequences. First, we introduce a theory of moral agency and apply it to the issue of behavioral changes caused by brain lesions. Second, we present a typology of brain lesions both with respect to their cause, their temporal development, and the potential for neural plasticity allowing for rehabilitation. We exemplify this scheme with case studies and outline major knowledge gaps that are relevant for clinical practice. Third, we analyze ethical pitfalls when trying to understand the brain-morality relation. In this way, our contribution addresses both researchers in neuroscience of ethics and clinicians who treat patients affected by brain lesions to better understand the complex ethical questions, which are raised by research and therapy of brain lesion patients. PMID- 25120024 TI - Effect of different iodine concentrations on well-differentiated thyroid cancer cell behavior and its inner mechanism. AB - High iodine intake might be an important factor in the promotion of thyroid cancer and the incidence of thyroid carcinoma has increased obviously these years especially in area of high iodine intake, though the mechanism of which remains unknown. The aim of present study was to gain more insight into the influence of different iodine concentrations on cell behavior, such as proliferation and migration, and to further investigate its molecular mechanism using two well differentiated thyroid cancer cell lines. Our study evaluated the effect of different iodine concentrations on cell behavior and investigated relevant molecules involved. The results indicated that iodine in vitro could promote the growth of thyroid cancer cells with the increase of iodine concentration in a specific range. Such effect may be related to signaling pathways as Akt and Erk and cytokine VEGF-A. PMID- 25120026 TI - Post-vaccinal distemper encephalitis in two Border Collie cross littermates. AB - CASE HISTORY: One 4.5-month-old male Border Collie cross presented with aggression and seizures in October 2006. A 16-month-old, female, spayed Border Collie cross presented with hypersalivation and a dropped jaw and rapidly became stuporous in September 2007. The dogs were littermates and developed acute neurological signs 5 and 27 days, respectively, after vaccination with different modified live vaccines containing canine distemper virus. HISTOPATHOLOGICAL FINDINGS: Sections of brain in both dogs showed evidence of encephalitis mainly centred on the grey matter of brainstem nuclei, where there was extensive and intense parenchymal and perivascular infiltration of histiocytes and lymphocytes. Intra-nuclear and intra-cytoplasmic inclusions typical of distemper were plentiful and there was abundant labelling for canine distemper virus using immunohistochemistry. DIAGNOSIS: Post-vaccinal canine distemper. CLINCIAL RELEVANCE: Post-vaccinal canine distemper has mainly been attributed to virulent vaccine virus, but it may also occur in dogs whose immunologic nature makes them susceptible to disease induced by a modified-live vaccine virus that is safe and protective for most dogs. PMID- 25120027 TI - [Subacute lower back pain and acute kidney failure in a 47-year old man]. AB - A 47-year-old man presented with subacute, low back pain and increased creatinine levels. A CT scan showed an extrinsic, bilateral compression of the ureters by a retroperitoneal mass with pronounced uptake of 18F-fluorodeoxyglucose in positron emission tomography. Histological findings were consistent with the diagnosis of retroperitoneal fibrosis. Urological decompression was performed. The initiated corticosteroids led to a rapid clinical improvement and regression of the retroperitoneal mass. A relapse occurred after tapering of corticosteroids with a prompt response to increase of the dosage. PMID- 25120028 TI - Higher apolipoprotein B levels are associated with earlier onset of first-ever atherosclerotic stroke. AB - BACKGROUND: Many studies have revealed apolipoproteins are risk factors for ischemic stroke, but the influence of apolipoproteins on onset age of first-ever atherosclerotic stroke has not been well investigated. METHODS: We recruited 357 qualified participants from consecutive patients with acute ischemic stroke who came to the stroke registry center in Sichuan Provincial People's Hospital, Chengdu, China. Patients were stratified into tertiles according to the distributions of apoB levels for large artery atherosclerosis (LAA) and small artery atherosclerosis (SAA) groups. The onset age of stroke was analyzed tripartitely in terms of early-onset group, the middling-onset group and the late onset group. Multinomial logistical regression was used to analyze the associations between the two. RESULTS: The risk of early-onset stroke increased monotonically with higher apoB levels (the second tertile, adjusted OR = 2.61, 95% CI 1.18-5.79 (p = 0.018); the third tertile, adjusted OR = 19.52, 95% CI 5.93 64.31 (p < 0.001)), and patients with the highest tertile of apoB levels had a 9.20 times (95% CI, 2.97-28.53, p < 0.001) increased risk of middling-onset stroke in reference to late onset of stroke. CONCLUSIONS: The present study suggests the higher the apolipoprotein B levels are, the earlier an atherosclerotic stroke might occur in a Chinese population. PMID- 25120030 TI - Flavonoid content, free radical scavenging and increase in xanthine oxidase inhibitory activity in Galgeun-tang following fermentation with Lactobacillus plantarum. AB - Galgeun-tang (GT) prior to and following fermentation with Lactobacillus plantarum was analyzed to determine the total polyphenol and flavonoid contents and the antioxidant activity. GT, fermented GT (FGT) and their three solvent partitioned fractions, which were prepared by successive partitioning with ethyl acetate (EtOAc), butanol (BuOH) and water, were evaluated for total polyphenol and flavonoid contents, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and xanthine oxidase (XO) inhibitory activity. Following fermentation, the total polyphenol content only increased slightly; however, the flavonoid content increased by 24.3%. The radical scavenging activity increased from 22.4 to 27.5% and the XO inhibitory activity increased from 20.2 to 62.4% at 500 ug/ml. The EtOAc fraction among the solvent-partitioned fractions demonstrated the highest total polyphenol and flavonoid contents, radical scavenging activities and XO inhibitory activity, and the quantity also markedly increased following fermentation. PMID- 25120031 TI - Maturation of Plasmodium falciparum in multiply infected erythrocytes and the potential role in malaria pathogenesis. AB - Erythrocytes containing two or more parasites, referred to here as multiply infected erythrocytes (MIEs), are common in the blood of humans infected by Plasmodium falciparum. It is necessary to study these cells closely because the excess numbers of parasites they contain suggest that they could be overloaded with virulence factors. Here, microscopic examinations of blood smears from patients showed that up to seven merozoites can successfully invade an erythrocyte and mature to ring stage. However, in vitro culture showed that only up to three parasites can mature to late schizont stage. These observations were made by culturing the parasites in erythrocytes containing hemoglobin AA (HbAA), HbAS, and HbSS. Biochemical analysis of saponin-concentrated culture suggests that more hemozoin is produced in a MIE than in a singly infected erythrocyte (SIE). Studies have shown that ingestion of excessive hemozoin destroys monocytes and neutrophils, which could impair the immune system. Cultured parasites were also examined by transmission electron microscopy, and it was found that the quantity of knobs was dramatically increased on the membranes of erythrocytes containing multiple schizonts, compared to those containing only one schizont. Knobs contain, among other things, P. falciparum erythrocyte membrane protein 1 (PfEMP1) complex which mediates sequestration and promotes severe malaria. These findings suggest that P. falciparum increases its virulence by producing MIEs. On sexual life cycle of the parasite, microphotographs are presented in this report showing, for the first time, that two gametocytes can develop in one erythrocyte; they are referred to here as twin gametocytes. It is not known whether they can infect mosquitoes. PMID- 25120032 TI - Acute visceral cysticercosis by Taenia hydatigena in lambs and treatment with praziquantel. AB - An acute outbreak of Taenia hydatigena cysticercosis, causing mortality in 5 of 21 (23.8%) female lambs, is reported. Gross post-mortem examinations and histology showed Cysticercus tenuicollis as the cause of death. Biochemical parameters in infected lambs confirmed severe hepatitis. Praziquantel, given once at 15 mg/kg body weight (bw), was administered and a dramatic improvement in the clinical condition and biochemical parameters was observed up to 30 days following treatment. PMID- 25120029 TI - Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort. AB - BACKGROUND AND AIMS: Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. METHODS: Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. RESULTS: Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. CONCLUSION: Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used. PMID- 25120033 TI - Elastic properties of chemical-vapor-deposited monolayer MoS2, WS2, and their bilayer heterostructures. AB - Elastic properties of materials are an important factor in their integration in applications. Chemical vapor deposited (CVD) monolayer semiconductors are proposed as key components in industrial-scale flexible devices and building blocks of two-dimensional (2D) van der Waals heterostructures. However, their mechanical and elastic properties have not been fully characterized. Here we report high 2D elastic moduli of CVD monolayer MoS2 and WS2 (~170 N/m), which is very close to the value of exfoliated MoS2 monolayers and almost half the value of the strongest material, graphene. The 2D moduli of their bilayer heterostructures are lower than the sum of 2D modulus of each layer but comparable to the corresponding bilayer homostructure, implying similar interactions between the hetero monolayers as between homo monolayers. These results not only provide deep insight into understanding interlayer interactions in 2D van der Waals structures but also potentially allow engineering of their elastic properties as desired. PMID- 25120034 TI - BRCA genetic counseling among at-risk Latinas in New York City: new beliefs shape new generation. AB - Despite the life-saving information that genetic counseling can provide for women at hereditary breast and/or ovarian cancer (HBOC) risk, Latinas disproportionately underuse such services. Understanding Latinas' beliefs and attitudes about BRCA genetic counseling may be the key to better health promotion within this underserved, at-risk group. We conducted 12 focus groups (N = 54) with at-risk Latina women in New York City, followed by 30 in-depth interviews among a subset of the focus group women. Both were professionally transcribed, translated where applicable and data analysis was completed by two coders trained in qualitative methods. Results revealed personal and community knowledge about BRCA genetic counseling was relatively low, although women felt largely positive about counseling. The main motivator to undergo genetic counseling was concerns about learning family members' cancer status, while the main barrier was competing demands. Generational differences were apparent, with younger women (approximately <55 years) reporting that they were more interested in educating themselves about counseling and other ways to prevent cancer. Younger women were also less likely to ascribe to traditionally Latino-centered cultural beliefs which could serve as barriers (e.g. machismo, fatalismo, destino) to undergoing genetic counseling. Participants were largely enthusiastic about educational efforts to increase awareness of genetic counseling among Latinos. Revealing the beliefs and attitudes of underserved Latinas may help shape culturally appropriate educational materials and promotion programs to increase BRCA genetic counseling uptake within this underrepresented community. PMID- 25120035 TI - A pilot study of BRCA mutation carriers' knowledge about the clinical impact of prophylactic-oophorectomy and views on fertility consultation: a single-center pilot study. AB - BRCA mutation carriers will experience early surgically induced menopause following prophylactic bilateral salpingo-oophorectomy (PBSO). This pilot study aimed to investigate their (1) knowledge about the clinical impact of PBSO; (2) views on fertility consultation (FC)/fertility preservation (FP) treatment; and (3) difficulties in conceiving compared to non-carriers. A cross-sectional, single institution web-survey was performed at a university-based IVF center. Women aged 18-50 years who were screened for BRCA gene mutations from 2005 to 2013 were recruited via mail. Forty-one BRCA-positive and 110 BRCA-negative women completed the survey (response rate: 50 %). The knowledge about the reproductive impact of PBSO was limited, with the majority of women in this highly educated sample only identifying the correct response 64 % of the time. Among BRCA mutation carriers, 24 (59 %) had positive views about FC/FP treatments. A larger proportion of women with no children at the time of BRCA testing, and those who were non-white tended to have positive views toward FP. Women with, versus without, BRCA mutations were more likely to have difficulty in conceiving (p = 0.08). This well-educated group had limited knowledge about the reproductive clinical impact of PBSO, or the benefit of a FP before PBSO. Most women with BRCA mutations were interested in FC/FP treatment if they had not completed childbearing at the time of screening. Targeted referrals for FC at the time of BRCA screening may help women improve knowledge and allow improved decision making about reproductive options. PMID- 25120036 TI - Mothers' experiences of genetic counselling in Johannesburg, South Africa. AB - Genetic counselling is offered in diverse settings, and patient reactions vary due to differences in personal, family and community beliefs, local healthcare settings, as well as cultural background. Together, these factors influence how individuals experience genetic counselling. This study aimed to describe and document the experiences of thirteen mothers, with children with Down syndrome, oculocutaneous albinism or haemophilia B, who had received genetic counselling at state hospitals in Johannesburg, South Africa. A qualitative research design drawing on principles of Interpretative Phenomenological Analysis was used. Four voice-recorded focus groups were conducted and the resulting data were analysed using thematic content analysis. Five themes were identified in the data: thrown into the unknown; a worthwhile experience; a break in communication; telling the family and the community; and spreading the word. It was seen that genetic counselling cannot be viewed as a singular experience, but rather as one which is influenced by mothers' lived experiences and their interactions with other healthcare services, family and community members. The results from this study showed that genetic services and conditions were poorly understood, that the experience of genetic counselling varied amongst mothers, and on-going patient support is needed particularly when addressing family and community members. Further research is needed to assess what information is valuable to individuals during genetic counselling and how to deliver this information in a contextually appropriate manner. Greater awareness of genetic conditions is also required amongst communities and healthcare professionals. Valuable insight was gained from this study which can be used to improve local training programmes and genetic counselling services in Johannesburg, and in South Africa. PMID- 25120037 TI - Clinical utility of chromosomal microarray analysis of DNA from buccal cells: detection of mosaicism in three patients. AB - Mosaic chromosomal abnormalities are relatively common. However, mosaicism may be missed due to multiple factors including failure to recognize clinical indications and order appropriate testing, technical limitations of diagnostic assays, or sampling tissue (s) in which mosaicism is either not present, or present at very low levels. Blood leukocytes have long been the "gold standard" sample for cytogenetic analysis; however, the culturing process for routine chromosome analysis can complicate detection of mosaicism since the normal cell line may have a growth advantage in culture, or may not be present in the cells that produce metaphases (the lymphocytes). Buccal cells are becoming increasingly utilized for clinical analyses and are proving to have many advantages. Buccal swabs allow for simple and noninvasive DNA collection. When coupled with a chromosomal microarray that contains single nucleotide polymorphic probes, analysis of buccal cells can maximize a clinician's opportunity to detect cytogenetic mosaicism. We present three cases of improved diagnosis of mosaic aberrations using buccal specimens for chromosomal microarray analysis. In each case, the aberration was either undetectable in blood or present at such a low level it likely could have gone undetected. These cases highlight the limitations of certain laboratory methodologies for identifying mosaicism. We also present practice implications for genetic counselors, including clinic workflow changes and counseling approaches based on increasing use of buccal samples. PMID- 25120039 TI - Water-displacement plethysmography: a technique for the simultaneous thermal manipulation and measurement of whole-hand and whole-foot blood flows. AB - The purpose of this project was to design, construct and validate water displacement plethysmographs for the forearm, hand and foot that could clamp segmental skin temperature whilst simultaneously measuring cutaneous blood flow. Two experiments were performed. In the first, the forearm plethysmograph was validated against a mercury-in-silastic plethysmograph under thermoneutral conditions, with and without forearm heating. Cutaneous vascular conductance was elevated almost three-fold by this treatment, however, there were no significant differences between the two forms of plethysmography in either state (P > 0.05). In study two, hand and foot blood flows were measured under clamped thermoneutral conditions, but with three local skin temperature treatments (5, 25, 40 degrees C). The hand had significantly higher blood flows than the foot at both 25 degrees C (4.07 versus 2.20 mL.100 mL( - 1).min( - 1); P < 0.05) and 40 degrees C (8.20 versus 4.47 mL.100 mL( - 1).min( - 1); P < 0.05). The foot was maximally constricted during the two lower temperatures, yet the cutaneous thermal sensitivity of the hand was almost two-fold greater (P < 0.05). This evidence supports the significant role played by these appendages in heat loss and conservation, and these plethysmographs will now be used to map cutaneous vascular responses (forearm, hand, calf, foot) across combinations of core and local skin temperatures. PMID- 25120038 TI - Use of a patient-entered family health history tool with decision support in primary care: impact of identification of increased risk patients on genetic counseling attendance. AB - Several barriers inhibit collection and use of detailed family health history (FHH) in primary care. MeTree, a computer-based FHH intake and risk assessment tool with clinical decision support, was developed to overcome these barriers. Here, we describe the impact of MeTree on genetic counseling (GC) referrals and attendance. Non-adopted, English speaking adults scheduled for a well-visit in two community-based primary-care clinics were invited to participate in an Implementation-Effectiveness study of MeTree. Participants' demographic characteristics and beliefs were assessed at baseline. Immediately after an appointment with a patient for whom GC was recommended, clinicians indicated whether they referred the patient and, if not, why. The study genetic counselor kept a database of patients with a GC recommendation and contacted those with a referral. Of 542 patients completing MeTree, 156 (29 %) received a GC recommendation. Of these, 46 % (n = 72) were referred and 21 % (n = 33) underwent counseling. Patient preferences, additional clinical information unavailable to MeTree, and an incomplete clinician evaluation of the FHH accounted for the 85 patients clinicians chose not to refer. Although MeTree identified a significant proportion of patients for whom GC was recommended, persistent barriers indicate the need for improved referral processes and patient and physician education about the benefits of GC. PMID- 25120042 TI - Blood donation: comparing individual characteristics, attitudes, and feelings of donors and nondonors. AB - The shortage of blood donors and increased demand for blood is an important health issue. Finding ways to increase donor recruitment and retention is a priority and, thus, an important area for research. This article aims to better understand donors and nondonors on the basis of their social responsibility, susceptibility to interpersonal influence, involvement in and attitude towards the blood donation issue, and their aroused feelings. The data from 345 completed surveys were collected via a web-based, self-administered method. Mean differences were examined and the conceptual model was tested via structural equation modeling. The findings provide important clarification of donation and nondonation behavior. PMID- 25120040 TI - Non-small-cell lung cancer resectability: diagnostic value of PET/MR. AB - PURPOSE: To assess the diagnostic performance of PET/MR in patients with non small-cell lung cancer. METHODS: Fifty consecutive consenting patients who underwent routine (18)F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy as the reference standard in 33 patients. In the remaining 17 nonsurgical patients, TNM was determined based on histology from biopsy, imaging results (CT and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy, sensitivity and specificity of the PET/MR in assessing the surgical resectability of primary tumour. The kappa statistic was used to assess interobserver agreement in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR findings, subsequently separately reviewed the PET/CT images for TNM staging. The generalized kappa statistic was used to determine intermodality agreement between PET/CT and PET/MR for TNM staging. RESULTS: ROC curve analysis showed that PET/MR had a specificity of 92.3 % and a sensitivity of 97.3 % in the determination of resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading ranged from substantial to perfect between the two readers (Cohen's kappa 0.646 - 1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage (Cohen's kappa 0.627 - 0.823). CONCLUSION: In lung cancer patients PET/MR appears to be a robust technique for preoperative staging. PMID- 25120041 TI - Machine learning models for the differential diagnosis of vascular parkinsonism and Parkinson's disease using [(123)I]FP-CIT SPECT. AB - PURPOSE: The study's objective was to develop diagnostic predictive models using data from two commonly used [(123)I]FP-CIT SPECT assessment methods: region-of interest (ROI) analysis and whole-brain voxel-based analysis. METHODS: We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson's disease (PD) who underwent [(123)I]FP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen [(123)I]FP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed. RESULTS: Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in [(123)I]FP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in [(123)I]FP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %. CONCLUSION: The predictive models built with ROI data and SPM data from [(123)I]FP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their applicability across centres. PMID- 25120043 TI - Jaypatient-induced service sabotage behavior: the issue of self-esteem of hospital nurses. AB - Worrying incidents exist where disgruntled nurses destroy good service quality through sabotage behavior. Previous studies report the organizational and environmental factors that might lead to service sabotage behaviors; here individual differences in proclivity to service sabotage within any given environment of managerial context are reported. The study first uses interviews to establish typologies of difficult patients. Regression analysis and ANOVA applied to survey data shows that low self-esteem in nurses leads to service sabotage behavior, and that these nurses are less mature both chronologically and emotionally, less experienced, and less educated than their more typical counterparts. PMID- 25120044 TI - Awareness of and attitudes toward direct-to-consumer prescription drug advertising among young adults. AB - This study examines awareness and knowledge of and attitudes toward direct-to consumer (DTC) prescription drug advertising among young adults between 18 and 24 years of age. The study finds that young adults are not as aware of prescription drug advertising as older consumers, however, they are aware of specific heavily advertised drugs, especially those for allergy medications, birth control, and sleep aids. Young adults hold mixed to negative views about advertising in general, and they do not view DTC prescription drug advertising as a beneficial source of information, nor do they believe such advertising serves to educate consumers. PMID- 25120045 TI - What is driving the growth in medical tourism? AB - The current study directly surveyed consumers on their experiences and consideration of medical tourism to test the variables thought to impact medical tourism. The sample was deployed to qSample's international traveler panel. The survey was completed by 68.5% of participants. Over a third of the respondents said they had considered medical tourism; 15% had actually traveled to another country for medical care. Dental treatment was named most often as the type of treatment pursued in another country. Cost was mentioned most frequently as the reason for medical tourism. Prior international travel emerged as an important factor. PMID- 25120046 TI - Direct-to-consumer advertising of predictive genetic tests: a health belief model based examination of consumer response. AB - Direct-to-consumer (DTC) advertising of predictive genetic tests (PGTs) has added a new dimension to health advertising. This study used an online survey based on the health belief model framework to examine and more fully understand consumers' responses and behavioral intentions in response to a PGT DTC advertisement. Overall, consumers reported moderate intentions to talk with their doctor and seek more information about PGTs after advertisement exposure, though consumers did not seem ready to take the advertised test or engage in active information search. Those who perceived greater threat from the disease, however, had significantly greater behavioral intentions and information search behavior. PMID- 25120047 TI - Attitudes and beliefs regarding direct-to-consumer advertising of pharmaceutical drugs: an exploratory comparison of physicians and pharmaceutical sales representatives. AB - Even with many changes in regulation in recent years, direct-to-consumer advertising (DTCA) of pharmaceutical drugs remains a complicated and contentious issue. Many in our society argue for increased legislation of DTCA while others believe that DTCA serves a useful purpose and should not be overregulated. This study was designed to compare attitudes and beliefs regarding DTCA held by two key stakeholder groups, physicians and pharmaceutical sales representatives. A questionnaire was created, pretested, and administered to 30 physicians and 30 pharmaceutical sales representatives to investigate these issues. Significant differences between these two groups were found and implications for DTCA are discussed. PMID- 25120048 TI - Flow cytometric analysis of SOX11: a new diagnostic method for distinguishing B cell chronic lymphocytic leukemia/small lymphocytic lymphoma from mantle cell lymphoma. AB - The differential diagnosis between mantle cell lymphoma (MCL) and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) is essential, since MCL usually has a more aggressive clinical course. By flow cytometry both MCL and B-CLL are CD19, CD20 and usually CD5 positive. However, ambiguities in other immune phenotypic markers of these lymphoma entities sometimes complicate the flow cytometric differential diagnosis. We here demonstrate that the transcription factor SOX11, which is highly up-regulated in most MCL, can be analyzed by flow cytometry. SOX11 protein could be consistently detected in ex vivo isolated MCL but not in B-CLL/SLL. Flow cytometry also enabled protein quantification, and SOX11 protein levels correlated with mRNA expression. We suggest that implementing detection of SOX11 in diagnostic flow cytometry would be beneficial for accurate and reliable diagnosis of MCL, especially for distinguishing cases of MCL and B-CLL/SLL with aberrant immune phenotypes, and for cases of rare cyclin D1 negative MCL. PMID- 25120049 TI - Use of a claims database to characterize and estimate the incidence rate for Castleman disease. AB - Castleman disease (CD) is a rare lymphoproliferative disorder affecting single (unicentric; UCD) or multiple (multicentric; MCD) lymph nodes. The incidence of this difficult to diagnose disease is poorly understood, as no International Classification of Diseases, Ninth Revision (ICD-9) code is available. This study utilized a unique strategy to estimate its incidence using two commercial claims databases, IMS LifeLinkTM and Truven Health Analytics MarketScan((r)). Patients with an index diagnosis of lymphadenopathy (ICD-9 code 785.6) were followed longitudinally for 1 year prior to and 2 years post-index diagnosis date. An algorithm that identifies potential patients with CD was developed to determine the incidence rate in person-years. The incidence rate for CD was calculated as 21 (IMS LifeLinkTM) and 25 (MarketScan((r))) per million person-years. Additionally, 23% of patients with CD were identified as potentially suffering from MCD. These results are consistent with the definition of an orphan disease, and the low incidence of the disease estimated in the literature. PMID- 25120050 TI - Incidence of secondary neoplasms in patients with acute promyelocytic leukemia treated with all-trans retinoic acid plus chemotherapy or with all-trans retinoic acid plus arsenic trioxide. AB - The incidence and pattern of secondary neoplasms in patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) containing regimens is not well described. We compared 160 patients with APL treated with ATRA plus idarubicin (n = 54) or ATRA plus arsenic trioxide (ATO) (n = 106) for the incidence of secondary cancers per unit time of follow-up. Median follow-up times for the two cohorts were 136 and 29 months, respectively. Nine patients developed secondary cancers in the chemotherapy group. These included two breast cancers, three myelodysplastic syndromes/acute myeloid leukemia, one vulvar cancer, one prostate cancer, one colon cancer and one soft tissue sarcoma. A melanoma and one pancreatic cancer developed in the ATO group. We conclude that treatment of patients with APL using the non-chemotherapy regimen of ATRA plus ATO is not associated with a higher incidence of secondary cancers (p = 0.29) adjusted for unit time of exposure. PMID- 25120053 TI - Erratum. PMID- 25120051 TI - Transmission of angioimmunoblastic T-cell lymphoma by bone marrow transplant. PMID- 25120052 TI - Underlying autoimmune diseases are not aggravated during treatment with lenalidomide in patients with mucosa-associated lymphoid tissue lymphoma. PMID- 25120055 TI - New limonoids from Hortia oreadica and unexpected coumarin from H. superba using chromatography over cleaning Sephadex with sodium hypochlorite. AB - Previous investigations of H. oreadica reported the presence of a wide spectrum of complex limonoids and dihydrocinnamic acids. Our interest in the Rutaceae motivated a reinvestigation of H. oreadica, H. brasiliana and H. superba searching for other secondary metabolites present in substantial amounts for taxonomic analysis. In a continuation of the investigation of the H. oreadica, three new limonoids have now been isolated 9alpha-hydroxyhortiolide A, 11beta hydroxyhortiolide C and 1(S*)-acetoxy-7(R*)-hydroxy-7-deoxoinchangin. All the isolated compounds from the Hortia species reinforce its position in the Rutaceae. With regard to limonoids the genus produces highly specialized compounds, whose structural variations do not occur in any other member of the Rutaceae, thus, it is evident from limonoid data that Hortia takes an isolated position within the family. In addition, H. superba afforded the unexpected coumarin 5-chloro-8-methoxy-psoralen, which may not be a genuine natural product. Solid-state cross-polarisation/magic-angle-spinning 13C nuclear magnetic resonance, X-Ray fluorescence and Field-emission gun scanning electron microscopy experiments show that the Sephadex LH-20 was modified after treatment with NaOCl, suggesting that when xanthotoxin (8-methoxy-psoralen) was extracted from cleaning of the gel column, chlorination of the aromatic system occurred. PMID- 25120054 TI - Bioevaluation of novel anti-biofilm coatings based on PVP/Fe3O4 nanostructures and 2-((4-ethylphenoxy)methyl)-N- (arylcarbamothioyl)benzamides. AB - Novel derivatives were prepared by reaction of aromatic amines with 2-(4 ethylphenoxymethyl)benzoyl isothiocyanate, affording the N-[2-(4 ethylphenoxymethyl) benzoyl]-N?-(substituted phenyl)thiourea. Structural elucidation of these compounds was performed by IR, NMR spectroscopy and elemental analysis. The new compounds were used in combination with Fe3O4 and polyvinylpyrrolidone (PVP) for the coating of medical surfaces. In our experiments, catheter pieces were coated by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The microbial adherence ability was investigated in 6 multi-well plates by using culture based methods. The obtained surfaces were also assessed for their cytotoxicity with respect to osteoblast cells, by using fluorescence microscopy and MTT assay. The prepared surfaces by advanced laser processing inhibited the adherence and biofilm development ability of Staphylococcus aureus and Pseudomonas aeruginosa tested strains while cytotoxic effects on the 3T3-E1 preosteoblasts embedded in layer shaped alginate hydrogels were not observed. These results suggest that the obtained medical surfaces, based on the novel thiourea derivatives and magnetic nanoparticles with a polymeric shell could represent a promising alternative for the development of new and effective anti-infective strategies. PMID- 25120056 TI - Synthesis and cytotoxic activity evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines. AB - A series of novel arylpiperazine derivatives was synthesized. The in vitro cytotoxic activities of all synthesized compounds against three human prostate cancer cell lines (PC-3, LNCaP, and DU145) were evaluated by a CCK-8 assay. Compounds 9 and 15 exhibited strong cytotoxic activities against LNCaP cells (IC50<5 MUM), and compound 8 (IC50=8.25 MUM) possessed the most potent activity against DU145 cells. However, these compounds also exhibited cytotoxicity towards human epithelial prostate normal cells RWPE-1. The structure-activity relationship (SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data. PMID- 25120057 TI - Comparative pharmacokinetics study of sinomenine in rats after oral administration of sinomenine monomer and Sinomenium acutum extract. AB - Various products containing sinomenine monomer and extracts of Sinomenium acutum have been widely applied in clinical treatments. The goal of the present study was to compare the pharmacokinetics of sinomenine in rats after oral administration of sinomenine monomer and Sinomenium acutum extract, and to attempt to explore potential component-component interactions between the constituents of this traditional Chinese herbal medicine. A reliable and specific reversed phase high performance liquid chromatography method was developed to analyze sinomenine in rat plasma. Pharmacokinetic parameters for sinomenine were processed by non-compartmental analysis. The results showed that the maximum concentration, the area under the concentration-time curve, clearance and the apparent volume of distribution of sinomenine in the Sinomenium acutum extract statistically differed from those of sinomenine monomer (p < 0.05); however, the mean residence time, time of peak concentration, and half-life did not show significant differences between the two groups. These findings suggested that some additional components in the Sinomenium acutum extract may decrease the absorption of sinomenine. The complex interactions between sinomenine and other components of the herbal extract could result in the altered pharmacokinetic behavior of sinomenine, which may subsequently cause different therapeutic and detoxification effects. PMID- 25120058 TI - Fused-ring derivatives of quinoxalines: spectroscopic characterization and photoinduced processes investigated by EPR spin trapping technique. AB - 10-Ethyl-7-oxo-7,10-dihydropyrido[2,3-f]quinoxaline derivatives, synthesized as promising biologically/photobiologically active compounds were characterized by UV/vis, FT-IR and fluorescent spectroscopy. Photoinduced processes of these derivatives were studied by EPR spectroscopy, monitoring in situ the generation of reactive intermediates upon UVA (lambdamax=365 nm) irradiation. The formation of reactive oxygen species and further oxygen- and carbon-centered radical intermediates was detected and possible reaction routes were suggested. To quantify the investigated processes, the quantum yields of the superoxide radical anion spin-adduct and 4-oxo-2,2,6,6-tetramethylpiperidine N-oxyl generation were determined, reflecting the activation of molecular oxygen by the excited state of the quinoxaline derivative. PMID- 25120061 TI - Proposed International League Against Epilepsy Classification 2010: new insights. AB - The International League Against Epilepsy (ILAE) Classification of Seizures in 1981 and the Classification of the Epilepsies, in 1989 have been widely accepted the world over for the last 3 decades. Since then, there has been an explosive growth in imaging, genetics and other fields in the epilepsies which have changed many of our concepts. It was felt that a revision was in order and hence the ILAE commissioned a group of experts who submitted the initial draft of this revised classification in 2010. This review focuses on what are the strengths and weaknesses of this new proposed classification, especially in the context of a developing country. PMID- 25120059 TI - Isocorydine derivatives and their anticancer activities. AB - In order to improve the anticancer activity of isocorydine (ICD), ten isocorydine derivatives were prepared through chemical structure modifications, and their in vitro and in vivo activities were experimentally investigated. 8-Amino isocorydine (8) and 6a,7-dihydrogen-isocorydione (10) could inhibit the growth of human lung (A549), gastric (SGC7901) and liver (HepG2) cancer cell lines in vitro. Isocorydione (2) could inhibit the tumor growth of murine sarcoma S180 bearing mice, and 8-acetamino-isocorydine (11), a pro-drug of 8-amino-isocorydine (8), which is instable in water solution at room temperature, had a good inhibitory effect on murine hepatoma H22-induced tumors. The results suggested that the isocorydine structural modifications at C-8 could significantly improve the biological activity of this alkaloid, indicating its suitability as a lead compound in the development of an effective anticancer agent. PMID- 25120060 TI - Expression of cytokeratin 8, vimentin, syndecan-1 and Ki-67 during human tooth development. AB - Spatio-temporal immunolocalizations of cytokeratin 8 (CK8), vimentin, syndecan-1 and Ki-67 were analyzed in ten human incisors and canine tooth germs between the 7th and 20th developmental weeks. CK8 expression was mild to moderate in the epithelial tooth parts, while it shifted from absent or mild in its mesenchymal parts, but few cells, sparsely distributed throughout the tooth germ, strongly expressed CK8. As development progressed, CK8 expression increased to strong in preameloblasts, while expression of vimentin increased to moderate in the epithelial and mesenchymal tooth parts, particularly in the dental papilla and sac. Co-expression of CK8 and vimentin was observed in some parts of the tooth germ, and was increasing in the differentiating preameloblasts and preodontoblasts. Syndecan-1 showed characteristic shift of expression from epithelial to mesenchymal tooth parts, being particularly strong in dental papilla, sac and cervical loops, while co-expression of Ki-67/syndecan-1 was strong in the dental papilla. Our study demonstrated spatio-temporal expression and restricted co-expression of the investigated markers, indicating participation of CK8 and vimentin in cell proliferation and migration, and differentiation of preodontoblasts and preameloblasts. Our data also suggest involvement of syndecan-1 in morphogenesis of the developing tooth crown and cervical loops, and together with CK8 and vimentin in differentiation of preameloblasts and preodontoblasts. PMID- 25120062 TI - Serum bisphenol A concentration and premature thelarche in female infants aged 4 month to 2-year. AB - OBJECTIVES: To estimate the association between serum bisphenol A and premature thelarche in female infants aged 4-mo to 2-y. METHODS: A total of 251 female infants (aged 4 mo to 2 y) with premature thelarche and 33 healthy age-matched control subjects were analyzed. All participants underwent physical examination and serum bisphenol A was measured by ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: Serum bisphenol A concentration in the premature thelarche group (3.48 ng/ml, 95%CI: 0.09-140.26) was significantly higher than that in the control group (1.70 ng/ml, 95%CI: 0.06-51.78) (p = 0.039). There was no correlation between age and serum bisphenol A (BPA) level. Univariate logistic regression analysis showed that serum BPA concentration positively associated with premature thelarche, and the effect of BPA fell down as the age grew. CONCLUSIONS: This hospital-based study implied that there is an association between serum BPA concentrations and premature thelarche. Additionally, serum BPA levels were markedly higher in infants aged 4-mo to 2-y old, raising a concern for public health authorities. PMID- 25120064 TI - Chikungunya virus transmission found in the United States: US health authorities brace for wider spread. PMID- 25120063 TI - ARID3B expression in primary breast cancers and breast cancer-derived cell lines. AB - BACKGROUND: ARID3B (AT-rich interaction domain 3) is a member of the family of ARID proteins, which constitutes evolutionarily conserved transcription factors implicated in normal development, differentiation, cell cycle regulation and chromatin remodeling. In addition, ARID3B has been linked to cellular immortalization, epithelial-mesenchymal transition (EMT) and tumorigenesis. Given the emerging role of ARID3B in tumor development, we examined its expression in primary patient-derived breast cancer samples and breast cancer-derived cell lines. METHODS: Immunohistochemistry (IHC) was used to detect ARID3B expression in 63 formalin-fixed paraffin-embedded (FFPE) invasive breast cancer samples. In addition, a panel of 6 (estrogen receptor-positive and -negative, ERBB2-positive and -negative) breast cancer-derived cell lines and immortalized non-tumorigenic epithelial breast cells were used for ARID3B expression analysis using RT-PCR. Specific primers and Western blotting were used to detect ARID3B isoforms. RESULTS: Using IHC, nuclear, cytoplasmic and low levels of membranous ARID3B staining were detected in all 63 primary invasive breast tumors. Nuclear ARID3B staining positively correlated with estrogen receptor (ER) status and negatively correlated with tumor grade, mitotic index and ERBB2 status of the patients. Increased nuclear expression of ARID3B was confirmed in breast cancer-derived cell lines expressing ERalpha. In addition, two out of three ERBB2-positive breast cancer cell lines were found to lack full length ARID3B. Three ARID3B isoforms were found to be present in normal breast epithelial cells as well as in breast cancer cells. CONCLUSION: We report a positive correlation between ER positivity and nuclear ARID3B expression in primary breast cancers, along with a negative correlation with the ERBB2 status. Very similar correlations were noted in breast cancer-derived cell lines. Since in the recent past ARID3B expression has increasingly been related to cancer-associated proteins and microRNAs, knowledge on ARID3B expression and function may be instrumental for gaining further insight into potentially important cancer-related networks. PMID- 25120068 TI - A symposium in honor of Peter B. Dervan, the 2014 ACS Chemical Biology Lectureship Award Winner. PMID- 25120070 TI - Lack of evidence that Tonkean macaques understand what others can hear. AB - By distinguishing the attentional cues of their mates, animals can learn what part of their environment is of potential interest. However, recognizing the attentional states of others through auditory perception appears to be difficult, since these states are generally not accompanied by ostensive signals liable to reveal them. In this context, one study found that rhesus macaques withhold their action when unobserved, then concluding that they know what others can hear. We replicated this study by testing 18 Tonkean macaques in an experimental setting where subjects had to choose between two boxes containing a food reward. One box made a noise when opened, and the other opened silently. An experimenter was present and could either have her back to subjects or be facing them. If subjects aimed to avoid attracting the experimenter's attention, they were expected to select the silent box while the experimenter's back was turned. Results showed that subjects did not discriminate between boxes, whatever the experimenter's position. We thus found no evidence that Tonkean macaques are able to take the auditory attentional states of a human into account. It is therefore premature to conclude that monkeys can establish a link between hearing and knowing. PMID- 25120072 TI - Lives of a journal. PMID- 25120073 TI - Effect of the cation on the interactions between alkyl methyl imidazolium chloride ionic liquids and water. AB - A systematic study of the interactions between water and alkyl methyl imidazolium chloride ionic liquids at 298.2 K, based on activity coefficients estimated from water activity measurements in the entire solubility range, is presented. The results show that the activity coefficients of water in the studied ILs are controlled by the hydrophilicity of the cation and the cation-anion interaction. To achieve a deeper understanding on the interactions between water and the ILs, COSMO-RS and FTIR spectroscopy were also applied. COSMO-RS was used to predict the activity coefficient of water in the studied ionic liquids along with the excess enthalpies, suggesting the formation of complexes between three molecules of water and one IL molecule. On the basis of quantum-chemical calculations, it is found that cation-anion interaction plays an important role upon the ability of the IL anion to interact with water. The changes in the peak positions/band areas of OH vibrational modes of water as a function of IL concentration were investigated, and the impact of the cation on the hydrogen-bonding network of water is identified and discussed. PMID- 25120071 TI - Development and performance of a 129-GHz dynamic nuclear polarizer in an ultra wide bore superconducting magnet. AB - OBJECTIVE: We sought to build a dynamic nuclear polarization system for operation at 4.6 T (129 GHz) and evaluate its efficiency in terms of (13)C polarization levels using free radicals that span a range of ESR linewidths. MATERIALS AND METHODS: A liquid helium cryostat was placed in a 4.6 T superconducting magnet with a 150-mm warm bore diameter. A 129-GHz microwave source was used to irradiate (13)C enriched samples. Temperatures close to 1 K were achieved using a vacuum pump with a 453-m(3)/h roots blower. A hyperpolarized (13)C nuclear magnetic resonance (NMR) signal was detected using a saddle coil and a Varian VNMRS console operating at 49.208 MHz. Samples doped with free radicals BDPA (1,3 bisdiphenylene-2-phenylallyl), trityl OX063 (tris{8-carboxyl-2,2,6,6-benzo(1,2 d:4,5-d)-bis(1,3)dithiole-4-yl}methyl sodium salt), galvinoxyl ((2,6-di-tert butyl-alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylidene)-p-tolyloxy), 2,2-diphenylpicrylhydrazyl (DPPH) and 4-oxo-TEMPO (4-Oxo-2,2,6,6-tetramethyl-1 piperidinyloxy) were assayed. Microwave dynamic nuclear polarization (DNP) spectra and solid-state (13)C polarization levels for these samples were determined. RESULTS: (13)C polarization levels close to 50 % were achieved for [1 (13)C]pyruvic acid at 1.15 K using the narrow electron spin resonance (ESR) linewidth free radicals trityl OX063 and BDPA, while 10-20 % (13)C polarizations were achieved using galvinoxyl, DPPH and 4-oxo-TEMPO. CONCLUSION: At this field strength free radicals with smaller ESR linewidths are still superior for DNP of (13)C as opposed to those with linewidths that exceed that of the (1)H Larmor frequency. PMID- 25120074 TI - Synthesis of NaLuF4-based nanocrystals and large enhancement of upconversion luminescence of NaLuF4:Gd, Yb, Er by coating an active shell for bioimaging. AB - A series of NaLuF4-based hexagonal phase upconversion nanocrystals (UCNs) were synthesized by a facile solvothermal method and the properties of the UCNs were investigated. The results show that the as-prepared nanocrystals exhibit pure hexagonal lattice structures, uniform morphologies, high monodispersities and excellent upconversion luminescence. The upconversion luminescence (UCL) intensities of the UCNs can be enhanced by coating with a shell of NaLuF4. More interestingly, the UCL intensities of active-shell coated nanocrystals (NaLuF4:Gd, Yb, Er@NaLuF4:Yb, Ho and NaLuF4:Gd, Yb, Er@NaLuF4:Yb) are remarkably higher than that of inert-shell coated nanocrystals (NaLuF4:Gd, Yb, Er@NaLuF4), and NaLuF4:Gd, Yb, Er@NaLuF4:Yb, Ho is higher than NaLuF4:Gd, Yb, Er@NaLuF4:Yb. The mechanisms of upconversion luminescence enhancement are discussed in detail. The bioimaging application of the nanocrystals showed that bright upconversion luminescence was observed when UCNs-labeled HeLa cells were excited with 980 nm light. This study presents a facile method for the synthesis of NaLuF4-based upconversion nanocrystals with intense luminescence that can be used as potential fluorescent probes for sensitive bioimaging, and the suggested mechanism could provide new insights into fabrication of upconversion materials with high upconversion fluorescence. PMID- 25120075 TI - Functional alterations in the dorsal raphe nucleus following acute and chronic ethanol exposure. AB - Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased anxiety-like behavior at both 24 h and 7 days post ethanol exposure. At 24 h post-ethanol exposure, we observed increased excitability and decreased spontaneous inhibitory transmission (inhibitory postsynaptic currents, IPSCs) in the DR. At 7 days post-ethanol exposure, we observed increased spontaneous and miniature excitatory transmission (excitatory postsynaptic currents, EPSCs). Because acute ethanol alters GABA transmission in other brain regions, we assessed the effects of ex vivo ethanol (50 mM) on miniature IPSCs (mIPSCs) in the DR 24-h post-ethanol exposure. Bath application of ethanol enhanced the amplitude of mIPSCs in cells from ethanol-naive and chronic intermittent ethanol-exposed (CIE) mice, but significantly enhanced the frequency of mIPSCs only in cells from CIE mice, suggesting that DR neurons are more sensitive to the inhibitory effects of acute ethanol following CIE. On the basis of these findings, we hypothesize that net excitation of DR neurons following chronic ethanol exposure contributes to enhanced anxiety during ethanol withdrawal, and that increased sensitivity of DR neurons to subsequent ethanol exposure may mediate acute ethanol's ability to relieve anxiety during ethanol withdrawal. PMID- 25120076 TI - High locomotor reactivity to novelty is associated with an increased propensity to choose saccharin over cocaine: new insights into the vulnerability to addiction. AB - Drug addiction is associated with a relative devaluation of natural or socially valued reinforcers that are unable to divert addicts from seeking and consuming the drug. Before protracted drug exposure, most rats prefer natural rewards, such as saccharin, over cocaine. However, a subpopulation of animals prefer cocaine over natural rewards and are thought to be vulnerable to addiction. Specific behavioral traits have been associated with different dimensions of drug addiction. For example, anxiety predicts loss of control over drug intake whereas sensation seeking and sign-tracking are markers of a greater sensitivity to the rewarding properties of the drug. However, how these behavioral traits predict the disinterest for natural reinforcers remains unknown. In a population of rats, we identified sensation seekers (HR) on the basis of elevated novelty-induced locomotor reactivity, high anxious rats (HA) based on the propensity to avoid open arms in an elevated-plus maze and sign-trackers (ST) that are prone to approach, and interaction with, reward-associated stimuli. Rats were then tested on their preference for saccharin over cocaine in a discrete-trial choice procedure. We show that HR rats display a greater preference for saccharin over cocaine compared with ST and HA whereas the motivation for the drug was comparable between the three groups. The present data suggest that high locomotor reactivity to novelty, or sensation seeking, by predisposing to an increased choice toward non-drug rewards at early stages of drug use history, may prevent the establishment of chronic cocaine use. PMID- 25120078 TI - Use of ultrasound in the insertion of a vascular closure device: a comparative retrospective study with the standard blind technique. AB - PURPOSE: To evaluate whether ultrasound (US) assistance can decrease the rate of complications related to the use of vascular closure devices (VCDs). MATERIALS AND METHODS: A retrospective comparative study was done on 150 consecutive patients who had a VCD inserted under US guidance after retrograde common-femoral artery (CFA) puncture. This group was compared to a historical control group of 150 consecutive patients who had the same VCDs inserted with the standard blind technique. After the procedures, patients were placed at bedrest for at least 6 h. Technical success, defined as correct deployment without adjunctive manual compression, blood count and US evaluation of the arterial puncture site was done at 24 h and at 3 months. Differences in terms of efficacy and safety were statistically evaluated using US guidance as a predictor for a lower complication rate. RESULTS: Technical success was achieved in 147/150 patients (98 %) in the study group vs. 141/150 cases (94 %) of the control group (p = 0.038). In three cases (2 %) adjunctive manual compression (<=5 min) was required. One pseudoaneurysm (0.65 %) occurred after 24 h, solved with manual compression. Six minor complications (4 %)--haematoma (n = 5; 3.35 %), recurrent wound bleeding (n = 1; 0.65 %)--were reported. In the control group four (2.65 %) major complications occurred: CFA occlusion managed with surgical bypass, CFA dissection solved by surgical bypass, two pseudoaneurysms solved with manual compression. Thirteen (8.65 %) minor complications were observed with haematoma (n = 10; 6.65 %), and recurrent wound bleeding (n = 3; 2.0 %). The comparative analysis of the total complication rate and major complication rate between the study group and the control group was statistically significant (p = 0.016 and p = 0.049, respectively). A 24-h evaluation showed a triphasic flow within the CFA in 150/150 patients (100 %) of the study group and in 146/150 cases (97.35 %) of the control group. CONCLUSION: VCD inserted under US guidance increases the success rate reducing the number of complications. PMID- 25120079 TI - Mammotome((r)) and EnCor ((r)): comparison of two systems for stereotactic vacuum assisted core biopsy in the characterisation of suspicious mammographic microcalcifications alone. AB - PURPOSE: The authors sought to compare the diagnostic performance of the Mammotome((r)) and EnCor((r)) vacuum-assisted breast biopsy (VABB) systems in the assessment of suspicious mammographic microcalcifications. MATERIALS AND METHODS: Between January 2011 and July 2012, a total of 169 VABB were performed by stereotactic guidance on a prone table. The Mammotome((r)) 11G (S1) or EnCor((r)) 10G (S2) probes were used randomly. Sampling time and the number of frustules collected were considered; sensitivity, specificity, diagnostic accuracy, positive and negative predictive value (PPV, NPV) of both procedures were evaluated, considering the final histological examination as reference (B1, B3, B5 lesions underwent surgical excision; B2 lesion were considered confirmed after a negative follow-up of at least 1 year). RESULTS: There were no statistically significant differences between the two groups of patients according to the number of procedures (S1 82/169; S2 87/169), average age, BIRADS category (4a, b), and average size of the lesions. The two systems did not differ statistically for correlation with the final histology (S1 k = 0.94 +/- 0.06; S2 k = 0.92 +/- 0.08) and underestimation of B3 lesions or in situ (S1 4.5%; S2 4.3%). Sensitivity, specificity, PPV, NPV, diagnostic accuracy of S1 and S2 were also not statistically different. The systems differed only in sampling time (S1 80; S2 63 s), but not in total procedure time. CONCLUSIONS: Our study confirms the effectiveness of VABB in the assessment of microcalcifications and highlights the lack of significant differences between the two systems in terms of diagnostic performance. PMID- 25120080 TI - Regarding hypertension treatment are we following worldwide tendencies? PMID- 25120077 TI - Blonanserin ameliorates phencyclidine-induced visual-recognition memory deficits: the complex mechanism of blonanserin action involving D3-5-HT2A and D1-NMDA receptors in the mPFC. AB - Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr(197) and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser(897) by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser(896) by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC. PMID- 25120081 TI - Impact of different obesity assessment methods after acute coronary syndromes. AB - BACKGROUND: Abdominal obesity is an important cardiovascular risk factor. Therefore, identifying the best method for measuring waist circumference (WC) is a priority. OBJECTIVE: To evaluate the eight methods of measuring WC in patients with acute coronary syndrome (ACS) as a predictor of cardiovascular complications during hospitalization. METHODS: Prospective study of patients with ACS. The measurement of WC was performed by eight known methods: midpoint between the last rib and the iliac crest (1), point of minimum circumference (2); immediately above the iliac crest (3), umbilicus (4), one inch above the umbilicus (5), one centimeter above the umbilicus (6), smallest rib and (7) the point of greatest circumference around the waist (8). Complications included: angina, arrhythmia, heart failure, cardiogenic shock, hypotension, pericarditis and death. Logistic regression tests were used for predictive factors. RESULTS: A total of 55 patients were evaluated. During the hospitalization period, which corresponded on average to seven days, 37 (67%) patients had complications, with the exception of death, which was not observed in any of the cases. Of these complications, the only one that was associated with WC was angina, and with every cm of WC increase, the risk for angina increased from 7.5 to 9.9%, depending on the measurement site. It is noteworthy the fact that there was no difference between the different methods of measuring WC as a predictor of angina. CONCLUSION: The eight methods of measuring WC are also predictors of recurrent angina after acute coronary syndromes. PMID- 25120082 TI - Resistance exercise restores endothelial function and reduces blood pressure in type 1 diabetic rats. AB - BACKGROUND: Resistance exercise effects on cardiovascular parameters are not consistent. OBJECTIVES: The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. METHODS: Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. RESULTS: A significant reduction in the maximum response of acetylcholine induced relaxation was observed in the sedentary diabetic group (78.1 +/- 2%) and an increase in the trained diabetic group (95 +/- 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 +/- 5 to 126.7 +/- 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 +/- 5 to 105.1 +/- 4 mmHg) as compared to the sedentary diabetic group. CONCLUSIONS: Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats. PMID- 25120083 TI - Evaluation of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin therapy in a southern Brazilian cohort. AB - BACKGROUND: Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. OBJECTIVE: To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. METHODS: Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 +/- 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. RESULTS: Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). CONCLUSIONS: Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations. PMID- 25120084 TI - Obesity does not lead to imbalance between myocardial phospholamban phosphorylation and dephosphorylation. AB - BACKGROUND: The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA. OBJECTIVE: To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation. METHODS: Male Wistar rats were randomly distributed into two groups: control (n = 14), fed with normocaloric diet; and obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP 1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed by Western blot. RESULTS: Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16. CONCLUSION: Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system. PMID- 25120085 TI - High-sensitivity C-reactive protein as a predictor of cardiovascular events after ST-elevation myocardial infarction. AB - BACKGROUND: The association between high-sensitivity C-reactive protein and recurrent major adverse cardiovascular events (MACE) in patients with ST elevation myocardial infarction who undergo primary percutaneous coronary intervention remains controversial. OBJECTIVE: To investigate the potential association between high-sensitivity C-reactive protein and an increased risk of MACE such as death, heart failure, reinfarction, and new revascularization in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. METHODS: This prospective cohort study included 300 individuals aged >18 years who were diagnosed with ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention at a tertiary health center. An instrument evaluating clinical variables and the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores was used. High-sensitivity C-reactive protein was determined by nephelometry. The patients were followed-up during hospitalization and up to 30 days after infarction for the occurrence of MACE. Student's t, Mann-Whitney, chi-square, and logistic regression tests were used for statistical analyses. P values of <=0.05 were considered statistically significant. RESULTS: The mean age was 59.76 years, and 69.3% of patients were male. No statistically significant association was observed between high sensitivity C-reactive protein and recurrent MACE (p = 0.11). However, high sensitivity C-reactive protein was independently associated with 30-day mortality when adjusted for TIMI [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.07 1.51; p = 0.005] and GRACE (OR, 1.26; 95% CI, 1.06-1.49; p = 0.007) risk scores. CONCLUSION: Although high-sensitivity C-reactive protein was not predictive of combined major cardiovascular events within 30 days after ST-elevation myocardial infarction in patients who underwent primary angioplasty and stent implantation, it was an independent predictor of 30-day mortality. PMID- 25120087 TI - Case 3/2014--81-year-old patient hospitalized for decompensated heart failure. PMID- 25120089 TI - Valvular heart team. PMID- 25120086 TI - Lipoprotein (a): structure, pathophysiology and clinical implications. AB - The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought. PMID- 25120088 TI - Bioresorbable vascular scaffold use in a case of in-stent restenosis. PMID- 25120090 TI - Insights of optical coherence tomography in renal artery fibromuscular dysplasia in a patient with spontaneous coronary artery dissection. PMID- 25120093 TI - Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses. AB - CMX001 (hexadecyloxypropyl-cidofovir, Brincidofovir) is a broad spectrum, lipid conjugate of cidofovir that is converted intracellularly into the active antiviral, cidofovir diphosphate. The lipid conjugation results in oral bioavailability, higher intracellular concentrations of active drug, lower plasma concentrations of cidofovir and increased antiviral potency against dsDNA viruses. PMID- 25120091 TI - Multivalent polymers for drug delivery and imaging: the challenges of conjugation. AB - Multivalent polymers offer a powerful opportunity to develop theranostic materials on the size scale of proteins that can provide targeting, imaging, and therapeutic functionality. Achieving this goal requires the presence of multiple targeting molecules, dyes, and/or drugs on the polymer scaffold. This critical review examines the synthetic, analytical, and functional challenges associated with the heterogeneity introduced by conjugation reactions as well as polymer scaffold design. First, approaches to making multivalent polymer conjugations are discussed followed by an analysis of materials that have shown particular promise biologically. Challenges in characterizing the mixed ligand distributions and the impact of these distributions on biological applications are then discussed. Where possible, molecular-level interpretations are provided for the structures that give rise to the functional ligand and molecular weight distributions present in the polymer scaffolds. Lastly, recent strategies employed for overcoming or minimizing the presence of ligand distributions are discussed. This review focuses on multivalent polymer scaffolds where average stoichiometry and/or the distribution of products have been characterized by at least one experimental technique. Key illustrative examples are provided for scaffolds that have been carried forward to in vitro and in vivo testing with significant biological results. PMID- 25120092 TI - Identification of a human neonatal immune-metabolic network associated with bacterial infection. AB - Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis. PMID- 25120094 TI - Neurogenin 3 is important but not essential for pancreatic islet development in humans. PMID- 25120096 TI - Orbital Lipomatosis: A Complication of Steroid Therapy in the Sweet Syndrome. AB - The description of a Sweet syndrome steroid dependant-induced orbital lipomatosis is reported. A 76-year-old-man with history of Sweet syndrome presented with severe bilateral proptosis (Hertel value, 25 mm) with decreased visual acuity and evoked potentials lengthened. A bilateral transpalpebral orbital decompression was performed by resection of intraorbital fat without bone removal. The surgery was uneventful. The volume of resected orbital fat was 15 ml for both sides. Proptosis reduction was 6 mm. Postoperative Hertel values were 19 mm, and evoked potentials were improved. The proptosis was managed successfully. Orbital lipectomy led to minimal sequelae and may be repeated if necessary in this case. PMID- 25120095 TI - Macrophage mTORC1 disruption reduces inflammation and insulin resistance in obese mice. AB - AIMS/HYPOTHESIS: Inflammatory factors secreted by macrophages play an important role in obesity-related insulin resistance. Being at the crossroads of a nutrient hormonal signalling network, the mammalian target of rapamycin complex 1 (mTORC1) controls important functions in the regulation of energy balance and peripheral metabolism. However, the role of macrophage mTORC1 in insulin resistance is still unclear. In the current study, we investigated the physiological role of macrophage mTORC1 in regulating inflammation and insulin sensitivity. METHODS: We generated mice deficient in the regulatory associated protein of mTOR (Raptor) in macrophages, by crossing Raptor (also known as Rptor) floxed mice (Raptor (flox/flox)) with mice expressing Cre recombinase under the control of the Lysm Cre promoter (Mac-Raptor (KO)). We fed mice chow or high-fat diet (HFD) and assessed insulin sensitivity in liver, muscle and adipose tissue. Subsequently, we measured inflammatory gene expression in liver and adipose tissue and investigated the role of Raptor deficiency in the regulation of inflammatory responses in peritoneal macrophages from HFD-fed mice or in palmitic acid stimulated bone marrow-derived macrophages (BMDMs). RESULTS: Mac-Raptor (KO) mice fed HFD had improved systemic insulin sensitivity compared with Raptor (flox/flox) mice. Macrophage Raptor deficiency reduced inflammatory gene expression in liver and adipose tissue, fatty liver and adipose tissue macrophage content in response to HFD. In peritoneal macrophages from mice fed with an HFD for 12 weeks, macrophage Raptor deficiency decreased inflammatory gene expression, through attenuation of the inactivation of Akt and subsequent inhibition of the inositol-requiring element 1alpha/clun NH2-terminal kinase nuclear factor kappa-light-chain-enhancer of activated B cells (IRE1alpha/JNK/NFkappaB) pathways. Similarly, mTOR inhibition as a result of Raptor deficiency or rapamycin treatment decreased palmitic acid-induced inflammatory gene expression in BMDMs in vitro. CONCLUSIONS/INTERPRETATION: The disruption of mTORC1 signalling in macrophages protects mice against inflammation and insulin resistance potentially by inhibiting HFD- and palmitic acid-induced IRE1alpha/JNK/NFkappaB pathway activation. PMID- 25120097 TI - Exercise for people with high cardiovascular risk. AB - BACKGROUND: When two or more cardiovascular risk factors occur in one individual, they may interact in a multiplicative way promoting cardiovascular disease. Exercise has proven to be effective in controlling individual risk factors but its effect on overall cardiovascular risk remains uncertain. OBJECTIVES: To assess the effects of exercise training in people with increased cardiovascular risk but without a concurrent cardiovascular disease on general cardiovascular mortality, incidence of cardiovascular events, and total cardiovascular risk. SEARCH METHODS: A search was conducted in CENTRAL (The Cochrane Library 2013, Issue 10 of 12), Ovid MEDLINE (1946 to week 2 November 2013), EMBASE Classic + EMBASE via Ovid (1947 to Week 47 2013), CINAHL Plus with Full Text via EBSCO (to November 2013), Science Citation Index Expanded (SCI-EXPANDED) (1970 to 22 November 2013), and Conference Proceedings Citation Index - Science (CPCI-S) (1990 to 22 November 2013) on Web of Science (Thomson Reuters). We did not apply any date or language restrictions. SELECTION CRITERIA: Randomized clinical trials comparing aerobic or resistance exercise training versus no exercise or any standard approach that does not include exercise. Participants had to be 18 years of age or older with an average 10-year Framingham risk score of 10% for cardiovascular disease over 10 years, or with two or more cardiovascular risk factors, and no history of cardiovascular disease. DATA COLLECTION AND ANALYSIS: The selection of studies and subsequent data collection process were conducted by two independent authors. Disagreements were solved by consensus. The results were reported descriptively. It was not possible to conduct a meta-analysis because of the high heterogeneity and high risk of bias in the included studies. MAIN RESULTS: A total of four studies were included that involved 823 participants, 412 in the exercise group and 411 in the control group. Follow-up of participants ranged from 16 weeks to 6 months. Overall, the included studies had a high risk of selection, detection, and attrition bias. Meta-analysis was not possible because the interventions (setting, type and intensity of exercise) and outcome measurements were not comparable, and the risk of bias in the identified studies was high. No study assessed cardiovascular or all-cause mortality or cardiovascular events as individual outcomes. One or more of the studies reported on total cardiovascular risk, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, blood pressure, body mass index, exercise capacity, and health-related quality of life but the available evidence was not sufficient to determine the effectiveness of exercise. Adverse events and smoking cessation were not assessed in the included studies. AUTHORS' CONCLUSIONS: Evidence to date is entirely limited to small studies with regard to sample size, short-term follow-up, and high risk of methodological bias, which makes it difficult to derive any conclusions on the efficacy or safety of aerobic or resistance exercise on groups with increased cardiovascular risk or in individuals with two or more coexisting risk factors. Further randomized clinical trials assessing controlled exercise programmes on total cardiovascular risk in individuals are warranted. PMID- 25120098 TI - Aberrant expression of B7-H3 in gastric adenocarcinoma promotes cancer cell metastasis. AB - B7-H3 belongs to the B7 superfamily, a group of molecules that costimulate or downmodulate T cell responses. Although it has been shown that B7-H3 can inhibit T cell responses, several studies, most of them performed in murine systems, found B7-H3 to act in a co-stimulatory manner. In addition, B7-H3 is also expressed in various human cancers and is correlated with the poor outcome of cancer patients. The functional role of B7-H3 in cancer is still controversially discussed. In the present study, we compared B7-H3 expression in normal gastric tissues and gastric cancer tissue specimens and determined the effects of low B7 H3 expression on the human gastric cancer cell line SGC-7901 by using RNAi. B7-H3 expression in gastric specimens was determined by tissue qPCR and immunohistochemisty. A SGC-7901 cell line with low B7-H3 expression was established by lentiviral-mediated RNA interference to investigate the effect of B7-H3 on cancer cell migration and invasion in vitro. By establishing an orthotopic transplantation gastric cancer mouse model, the effect of B7-H3 on cell migration and invasion was studied in vivo. B7-H3 expression was significantly higher in the gastric cancer group than that in the normal gaster group. B7-H3 knockdown by RNA interference decreased cell migration and Transwell invasion up to 50% in vitro. In the orthotopic transplantation gastric cancer mouse model, the effect of inhibiting metastasis by knockdown of B7-H3 was assessed in terms of the average postmortem abdominal visceral metastatic tumor weight. The results revealed that inhibition of B7-H3 expression reduced gastric cancer metastasis in vivo. In conclusion, B7-H3 is aberrantly expressed in gastric cancer. In addition to modulating tumor immunity, B7-H3 may have a novel role in regulating SGC-7901 cell metastasis. PMID- 25120099 TI - Genetic characterization and phylogenetic relationships based on 18S rRNA and ITS1 region of small form of canine Babesia spp. from India. AB - Canine babesiosis is a vector borne disease caused by intra-erythrocytic apicomplexan parasites Babesia canis (large form) and Babesia gibsoni (small form), throughout the globe. Apart from few sporadic reports on the occurrence of B. gibsoni infection in dogs, no attempt has been made to characterize Babesia spp. of dogs in India. Fifteen canine blood samples, positive for small form of Babesia, collected from northern to eastern parts of India, were used for amplification of 18S rRNA gene (~1665bp) of Babesia sp. and partial ITS1 region (~254bp) of B. gibsoni Asian genotype. Cloning and sequencing of the amplified products of each sample was performed separately. Based on sequences and phylogenetic analysis of 18S rRNA and ITS1 sequences, 13 were considered to be B. gibsoni. These thirteen isolates shared high sequence identity with each other and with B. gibsoni Asian genotype. The other two isolates could not be assigned to any particular species because of the difference(s) in 18S rRNA sequence with B. gibsoni and closer identity with Babesiaoccultans and Babesiaorientalis. In the phylogenetic tree, all the isolates of B. gibsoni Asian genotype formed a separate major clade named as Babesia spp. sensu stricto clade with high bootstrap support. The two unnamed Babesia sp. (Malbazar and Ludhiana isolates) clustered close together with B. orientalis, Babesia sp. (Kashi 1 isolate) and B. occultans of bovines. It can be inferred from this study that 18S rRNA gene and ITS1 region are highly conserved among 13 B. gibsoni isolates from India. It is the maiden attempt of genetic characterization by sequencing of 18S rRNA gene and ITS1 region of B. gibsoni from India and is also the first record on the occurrence of an unknown Babesia sp. of dogs from south and south-east Asia. PMID- 25120100 TI - In-silico analysis of claudin-5 reveals novel putative sites for post translational modifications: Insights into potential molecular determinants of blood-brain barrier breach during HIV-1 infiltration. AB - The blood-brain barrier (BBB) poses a huge challenge and is a serious issue in deciphering the pathophysiology of central nervous system disorders. Endothelial tight junctions play an essential role in maintaining the integrity of the BBB. Post-translational modifications (PTMs) in endothelial tight junction proteins are known to cause deleterious functional impairment and possible disruptions in BBB integrity. PTMs in tight junction proteins play an important role in human immunodeficiency virus type 1 (HIV-1) entry through the BBB. Human claudin-5 is one of the highly expressed brain endothelial tight junction protein and various PTMs in claudin-5 are expected to aid HIV-1 in crossing the BBB. A precise characterization of PTMs in claudin-5 is important for understanding its role in HIV-1 brain infiltration. In this study, we have examined post-translational crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation sites in claudin-5, which could alter claudin-5's ability to maintain BBB integrity. To the best of our knowledge, this is the first report on claudin 5 protein that suggests a novel interplay between potential PTM sites. PTMs of predicted residues in claudin-5, suggested in this study, can serve as compelling targets for potential therapeutic agents against HIV-1 induced neuropathogenesis. Further site-specific experimental studies in this aspect are highly recommended. PMID- 25120101 TI - Activated cytotoxic T-lymphocyte immunotherapy is effective for advanced oral and maxillofacial cancers. AB - Conventional cancer treatments are surgery, radiotherapy, and chemotherapy, but treatment efficiency is insufficient and cancer recurrence is common. Immunotherapy has been added as an important cancer treatment component, but no reports on its efficacy in oral and maxillofacial cancers exist. We evaluated the clinical efficacy of adoptive immunotherapy using ex vivo-activated cytotoxic T lymphocytes (CTL) in the treatment of 7 patients with advanced oral and maxillofacial cancers with stage IV disease at diagnosis. The mean follow-up period was 26.2 months. Phenotype of the lymphocyte assay revealed that the percentage of CD4(+) T cells decreased and that of CD8(+) T cells increased among infused lymphocytes compared to that in unstimulated peripheral blood mononuclear cells (PBMCs), and infused lymphocytes produced a significantly higher level of IFN-gamma than PBMCs or tumor cells alone. In a representative patient who refused surgery tumor regression was confirmed after CTL infusion. Computed tomography clearly indicated a significant reduction in tumor size followed by the complete disappearance of the tumor. Histological examination showed that the cancers in patients receiving CTL therapy were heavily infiltrated with lymphocytes. The other 2 patients who received CTL therapy as adjuvant therapy showed neither recurrent disease nor new disease lesions. The 1-year survival rates showing response and those with progressive disease were 100 and 25%, respectively. Moreover, no significant adverse reactions were reported during the study period. CTL therapy remains in the early stages of treatment options, but it has potential as a valuable treatment and improvement of quality of life for patients with otherwise incurable cancers. PMID- 25120103 TI - Determination of psychotropic use in children and adolescents from a prescription database: methodological issues. PMID- 25120102 TI - Inhibition of form-deprivation myopia by a GABAAOr receptor antagonist, (1,2,5,6 tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), in guinea pigs. AB - PURPOSE: To investigate the effects of the relatively selective GABAAOr receptor antagonist (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on form deprivation myopia (FDM) in guinea pigs. METHODS: A diffuser was applied monocularly to 30 guinea pigs from day 10 to 21. The animals were randomized to one of five treatment groups. The deprived eye received daily sub-conjunctival injections of 100 MUl TPMPA at a concentration of (i) 0.03 %, ( ii) 0.3 %, or (iii) 1 %, a fourth group (iv) received saline injections, and another (v) no injections. The fellow eye was left untreated. An additional group received no treatment to either eye. Prior to and at the end of the treatment period, refraction and ocular biometry were performed. RESULTS: Visual deprivation produced relative myopia in all groups (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001); myopia was less in deprived eyes receiving either 0.3 % or 1 % TPMPA (saline = -4.38 +/- 0.57D, 0.3 % TPMPA = -3.00 +/- 0.48D, P < 0.01; 1 % TPMPA = -0.88 +/- 0.51D, P < 0.001). The degree of axial elongation was correspondingly less (saline = 0.13 +/- 0.02 mm, 0.3 % TPMPA = 0.09 +/- 0.01 mm, P < 0.01, 1 % TPMPA = 0.02 +/- 0.01 mm, P < 0.001) as was the VC elongation (saline = 0.08 +/- 0.01 mm, 0.3 % TPMPA = 0.05 +/- 0.01 mm, P < 0.01, 1 % TPMPA = 0.01 +/- 0.01 mm; P < 0.001). ACD and LT were not affected (one-way ANOVA, P > 0.05). One percent TPMPA was more effective at inhibiting myopia than 0.3 % (P < 0.01), and 0.03 % did not appreciably inhibit the myopia (0.03 % TPMPA versus saline, P > 0.05). CONCLUSIONS: Sub-conjunctival injections of TPMPA inhibit FDM in guinea pig models in a dose-dependent manner. PMID- 25120104 TI - Functional profile of a novel modulator of serotonin, dopamine, and glutamate neurotransmission. AB - RATIONALE: Schizophrenia remains among the most prevalent neuropsychiatric disorders, and current treatment options are accompanied by unwanted side effects. New treatments that better address core features of the disease with minimal side effects are needed. OBJECTIVES: As a new therapeutic approach, 1-(4 fluoro-phenyl)-4-((6bR, 10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one (ITI-007) is currently in human clinical trials for the treatment of schizophrenia. Here, we characterize the preclinical functional activity of ITI-007. RESULTS: ITI-007 is a potent 5-HT2A receptor ligand (K i = 0.5 nM) with strong affinity for dopamine (DA) D2 receptors (K i = 32 nM) and the serotonin transporter (SERT) (K i = 62 nM) but negligible binding to receptors (e.g., H1 histaminergic, 5-HT2C, and muscarinic) associated with cognitive and metabolic side effects of antipsychotic drugs. In vivo it is a 5-HT2A antagonist, blocking (+/-)-2,5-dimethoxy-4 iodoamphetamine hydrochloride (DOI)-induced headtwitch in mice with an inhibitory dose 50 (ID50) = 0.09 mg/kg, per oral (p.o.), and has dual properties at D2 receptors, acting as a postsynaptic D2 receptor antagonist to block D-amphetamine hydrochloride (D-AMPH) hyperlocomotion (ID50 = 0.95 mg/kg, p.o.), yet acting as a partial agonist at presynaptic striatal D2 receptors in assays measuring striatal DA neurotransmission. Further, in microdialysis studies, this compound significantly and preferentially enhances mesocortical DA release. At doses relevant for antipsychotic activity in rodents, ITI-007 has no demonstrable cataleptogenic activity. ITI-007 indirectly modulates glutamatergic neurotransmission by increasing phosphorylation of GluN2B-type N-methyl-D aspartate (NMDA) receptors and preferentially increases phosphorylation of glycogen synthase kinase 3beta (GSK-3beta) in mesolimbic/mesocortical dopamine systems. CONCLUSION: The combination of in vitro and in vivo activities of this compound support its development for the treatment of schizophrenia and other psychiatric and neurologic disorders. PMID- 25120106 TI - Potential sensitivity of bias analysis results to incorrect assumptions of nondifferential or differential binary exposure misclassification. AB - BACKGROUND: Results of bias analyses for exposure misclassification are dependent on assumptions made during analysis. We describe how adjustment for misclassification is affected by incorrect assumptions about whether sensitivity and specificity are the same (nondifferential) or different (differential) for cases and noncases. METHODS: We adjusted for exposure misclassification using probabilistic bias analysis, under correct and incorrect assumptions about whether exposure misclassification was differential or not. First, we used simulated data sets in which nondifferential and differential misclassification were introduced. Then, we used data on obesity and diabetes from the National Health and Nutrition Examination Survey (NHANES) in which both self-reported (misclassified) and measured (true) obesity were available, using literature estimates of sensitivity and specificity to adjust for bias. The ratio of odds ratio (ROR; observed odds ratio divided by true odds ratio) was used to quantify magnitude of bias, with ROR = 1 signifying no bias. RESULTS: In the simulated data sets, under incorrect assumptions (eg, assuming nondifferential misclassification when it was truly differential), results were biased, with RORs ranging from 0.18 to 2.46. In NHANES, results adjusted based on incorrect assumptions also produced biased results, with RORs ranging from 1.26 to 1.55; results were more biased when making these adjustments than when using the misclassified exposure values (ROR = 0.91). CONCLUSIONS: Making an incorrect assumption about nondifferential or differential exposure misclassification in bias analyses can lead to more biased results than if no adjustment is performed. In our analyses, incorporating uncertainty using probabilistic bias analysis was not sufficient to overcome this problem. PMID- 25120105 TI - Etazolate, a phosphodiesterase-4 enzyme inhibitor produces antidepressant-like effects by blocking the behavioral, biochemical, neurobiological deficits and histological abnormalities in hippocampus region caused by olfactory bulbectomy. AB - RATIONALE: Olfactory bulbectomy (OBX) is a widely used model for antidepressant screening and known to induce neurodegeneration in several brain areas. Our earlier studies demonstrated that etazolate produced antidepressant-like effects in behavioral despair models of depression; however, the potential role of etazolate on behavior and morphological changes in the hippocampus region along with its underlying mechanism(s) following OBX has not been adequately addressed. OBJECTIVES: We evaluated if etazolate could protect against OBX-induced depression-like behavioral deficits and neurodegeneration. The possible underlying mechanism of etazolate in OBX model was also investigated. METHODS: The effects of etazolate were measured in a battery of behavioral paradigms, including the forced swim test (FST), sucrose consumption, open arm activity in elevated plus maze (EPM), and hyperemotionality tests. The underlying mechanisms were investigated by measuring serum corticosterone (CORT), cyclic adenosine monophosphate (cAMP), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and oxidative/nitrosative stress (lipid peroxidation and nitrite) levels and antioxidant enzymes, like reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels in the hippocampus. RESULT: OBX rats showed depression-like behavior anomalies in behavioral paradigms. OBX rats also showed high CORT and decreased cAMP, phosphorylated CREB (pCREB), and BDNF levels. Additionally, we found increased oxidative/nitrosative stress and reduced antioxidant enzyme levels in the hippocampus. Histopathological analysis showed morphological changes and neuronal loss in the hippocampus. Etazolate (0.5 and 1 mg/kg) attenuated the OBX-induced behavioral, biochemical, neurobiological, and histopathological alterations. CONCLUSION: The aforesaid results suggest that etazolate produces an antidepressant-like effect and neuroprotection in OBX, which is possibly mediated by modulating biochemical and neurobiological markers in the hippocampus. PMID- 25120107 TI - Visfatin -948G/T and resistin -420C/G polymorphisms in Egyptian type 2 diabetic patients with and without cardiovascular diseases. AB - Diabetes mellitus is one of the main threats to human health in the 21st century. Visfatin/Nampt and resistin are novel adipokines that have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) complication. Several genetic studies have shown inconsistent results regarding association of visfatin/Nampt gene (NAMPT) and resistin gene (RETN) polymorphisms with T2DM and CVD complications. Here, we investigate whether NAMPT -948G/T and RETN -420C/G polymorphisms are associated with T2DM, its CVD complications, and serum adipokines levels in 90 Egyptian diabetic patients (44 without CVD and 46 with CVD) along with 60 healthy control subjects. Higher frequencies of NAMPT 948G/G and RETN -420G/G were observed among T2DM patients compared with controls. Furthermore, the frequencies of these genotypes were significantly higher in T2DM patients with CVD than those without CVD. Both NAMPT -948G/G and RETN -420G/G genotypes and G alleles were significantly associated with T2DM and CVD in Egyptian diabetic patients. Moreover, serum visfatin/Nampt and resistin levels were markedly elevated in T2DM patients, with the highest values observed in G/G genotypes among T2DM patients with CVD. In addition, positive correlations were observed between plasma adipokines levels and CVD risk factors. In conclusion, our data suggests that genetic variations in NAMPT -948G/T and RETN -420C/G may contribute to the disposition for T2DM and its CVD complications in Egyptian patients. However, further studies with greater sample size should be performed to verify these results. PMID- 25120108 TI - Screening older Latinos for dementia in the primary care setting. AB - The purpose was to compare the Spanish language picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR) and the Mini Mental State Exam (MMSE) in identifying very mild dementia among Spanish speaking Latino patients. The tests and an independent diagnostic assessment were administered to 112 Latino patients free of medically diagnosed dementia from an urban primary care clinic. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to examine differences in the operating characteristics of the pFCSRT+IR and the MMSE. Cut scores were manipulated to equate sensitivities (specificities) at clinically relevant values to compare differences in specificities (sensitivities) using the Pearson Chi Square test. Youden's index was used to select the optimal cut scores. Twenty-four of the 112 primary care patients (21%) received a research dementia diagnosis, indicating a substantial burden of unrecognized dementia. MMSE scores but not free recall scores were associated with years of education in patients free of dementia. AUC was significantly higher for free recall than for MMSE. Free recall performed significantly better than the MMSE in sensitivity and in specificity. Using optimal cut scores, patients with impaired free recall were 10 times more likely to have dementia than patients with intact recall, and patients with impaired MMSE scores were 4.5 times more likely to have dementia than patients with intact scores. These results suggest that the Spanish language pFCSRT+IR may be an effective tool for dementia screening in educationally diverse Latino primary care populations. PMID- 25120111 TI - [Mental health services from a public health perspective]. PMID- 25120112 TI - [Mental health care reform: the end or still in progress?]. PMID- 25120109 TI - Exercise in ZDF rats does not attenuate weight gain, but prevents hyperglycemia concurrent with modulation of amino acid metabolism and AKT/mTOR activation in skeletal muscle. AB - PURPOSE: Protein metabolism is altered in obesity, accompanied by elevated plasma amino acids (AA). Previously, we showed that exercise delayed progression to type 2 diabetes in obese ZDF rats with maintenance of beta cell function and reduction in hyperglucocorticoidemia. We hypothesized that exercise would correct the abnormalities we found in circulating AA and other indices of skeletal muscle protein metabolism. METHODS: Male obese prediabetic ZDF rats (7-10/group) were exercised (swimming) 1 h/day, 5 days/week from ages 6-19 weeks, and compared with age-matched obese sedentary and lean ZDF rats. RESULTS: Food intake and weight gain were unaffected. Protein metabolism was altered in obese rats as evidenced by increased plasma concentrations of essential AA, and increased muscle phosphorylation (ph) of Akt(ser473) (187%), mTOR(ser2448) (140%), eIF4E-binding protein 1 (4E-BP1) (111%), and decreased formation of 4E-BP1*eIF4E complex (75%, 0.01 <= p <= 0.05 for all measures) in obese relative to lean rats. Exercise attenuated the increase in plasma essential AA concentrations and muscle Akt and mTOR phosphorylation. Exercise did not modify phosphorylation of S6K1, S6, and 4E BP1, nor the formation of 4E-BP1*eIF4E complex, mRNA levels of ubiquitin or the ubiquitin ligase MAFbx. Positive correlations were observed between ph-Akt and fed circulating branched-chain AA (r = 0.56, p = 0.008), postprandial glucose (r = 0.42, p = 0.04) and glucose AUC during an IPGTT (r = 0.44, p = 0.03). CONCLUSION: Swimming exercise-induced attenuation of hyperglycemia in ZDF rats is independent of changes in body weight and could result in part from modulation of muscle AKT activation acting via alterations of systemic AA metabolism. PMID- 25120113 TI - [Primary mental healthcare reform in Quebec and the role and coordination strategies of general practitioners]. AB - OBJECTIVES: The health and mental health systems in Quebec have recently been substantially transformed. At the heart of this restructuring, reforms aimed to strengthen primary care and to better integrate services, which are central trends internationally. This article summarizes Quebec's primary health and mental health reforms. It also presents the key role of general practitioners in the treatment of mental health disorders and their coordination strategies with the mental health care resources in the province. METHODS: Numerous documents on the Quebec health and mental health reforms and the international literature on primary mental health care were consulted for this study. Information on general practitioner roles in mental health were based on administrative data from the Regie de l'assurance maladie du Quebec (RAMQ) for all medical procedures performed in 2006. The data was compared with the results of a survey realized in the same year with 398 general practitioners in Quebec. Complementary qualitative data was collected through one hour interviews on a subsample of 60 of those general practitioners. RESULTS: The central aim of the Quebec healthcare reform was to improve services integration by implementing local healthcare networks. A population health approach and a hierarchical service provision were promoted. For a better access and continuity of care, family medicine groups and network clinics were also developed. The mental health reform (Action Plan in Mental Health, 2005-2010) was launched in this general context. It prioritized the consolidation of primary care and shared-care (i.e. increased networking between general practitioners and psychosocial workers and psychiatrists) by reinforcing the role of general practitioners in mental health, developing mental health interdisciplinary teams in primary care and adding a psychiatrist-respondent function in each Quebec local healthcare network. In mental health, general practitioners played a central role as the primary source of care and networking to other resources either primary or specialized health care services. Between 20 25% of visits to general practitioners are related to mental health problems. Nearly all general practitioners manage common mental disorders and believed themselves competent to do so; however, the reverse is true for the management of serious mental disorders. Mainly general practitioners practiced in silo without much relation with the mental health care resources. Numerous factors were found to influence the management of mental health problems: patients' profiles (e.g. the complexity of mental health problems, concomitant disorders), individual characteristics of the general practitioners (e.g. informal network, training); professional culture (e.g. formal clinical mechanisms), the institutional setting (e.g. multidisciplinary or not) and organizations of services (e.g. policies). CONCLUSION: Unfortunately, the Quebec health and mental health care reforms have not been fully implemented yet. Family medicine groups and networks clinics, primary mental health teams and psychiatrists-respondent are not optimally operational and therefore, are not having a significant outcome. Support mechanisms to help implement the reforms were not prioritized. Hindering factors should be identified and minimized to increase positive changes in the health and mental health systems. This article concludes on the importance of implementing continuums of care, especially local healthcare networks and best practices in mental health. Furthermore, strong strategies to support the implementation of changes should always accompany sweeping reforms. PMID- 25120110 TI - The effect of green tea extract supplementation on exercise-induced oxidative stress parameters in male sprinters. AB - BACKGROUND: Although research suggests that antioxidant supplementation can protect against exercise-induced muscle damage and oxidative stress, also delayed post-exercise muscle recovery and hindered adaptation to training were reported in the supplemented athletes. PURPOSE: The purpose of the study was to evaluate the effects of green tea extract (GTE) supplementation on selected blood markers of oxidative stress and muscle damage in sprinters during preparatory phase of their training cycle. METHODS: Sixteen sprinters participated in a double-blind, randomized, placebo (PL)-controlled crossover study, including two 4-week treatment periods with PL and GTE (980 mg polyphenols daily). The sprinters performed two repeated cycle sprint tests (RST; 4 * 15 s, with 1-min rest intervals), after PL and GTE supplementation. Blood was sampled before (at rest), 5 min after RST, and after the 24-h recovery. The activities of superoxide dismutase (SOD) and glutathione peroxidase were measured in erythrocytes, and total polyphenols, total antioxidant capacity (TAC), uric acid (UA), albumin (AL), malondialdehyde (MDA), and creatine kinase (CK) were determined in blood plasma. RESULTS: Repeated cycle sprint test performed after PL induced an increase in MDA, TAC, and SOD. Moreover, an increase in UA, AL, and CK was observed after RST irrespective of experimental conditions (PL, GTE). Supplementation with GTE caused an increase in total polyphenols and TAC at rest, and a decrease in MDA and SOD after RST. No significant changes in sprint performance were noted after GTE, as compared to PL. CONCLUSIONS: Supplementation with GTE prevents oxidative stress induced by RST in sprinters. Furthermore, GTE supplementation does not seem to hinder training adaptation in antioxidant enzyme system. On the other hand, neither prevention of exercise-induced muscle damage, nor an improvement in sprint performance is noted after GTE administration. PMID- 25120114 TI - [What's a framework without its frame?]. AB - OBJECTIVE: In 2005, the Quebec Ministry of Health launched a major reform of its Mental Health services. This reform aimed both the type of services (collaborative care; community care) and the structure (shift to primary care venues) in which these services where offered. Any major reform must be supported by different means. This article will review which means are best suited to do this and up to what point these where used to support the implementation of the reform. It will also help in preparing for the upcoming launch of the next Mental Health Plan of Action by the Quebec Ministry of Health. METHOD: The authors exchanged on several occasions on their observations and thoughts on the subject. RESULTS: Any major health reform must be supported by different means. Some are related to legislation or government policies, but these alone are insufficient. Others means include academic and continuing development actions, service accreditation or certification and user participation in policy and implementation stages of service delivery. CONCLUSION: If some means of support are easily invested, some are neglected. An effort should be made to use all available means to support the upcoming Plan of Action. User involvement seems particularly promising. PMID- 25120115 TI - [Policies and mental health action plans in OECD: lessons for Quebec?]. AB - OBJECTIVES: The objectives of this research are: 1) to provide a conceptual framework for analyzing mental health policies; 2) to compare mental health policies across a sample of OECD jurisdictions; 3) to describe configurations of mental health policies; 4) to identify practical implications for the Province of Quebec. METHODS: DESIGN: This research is a comparative synthetic study of mental health policies. SAMPLING: The web sites of the Ministries of health of the thirty-four OECD countries and ten Canadian Provinces were searched for mental health policies proposed within the last fifteen years. Twenty one such policies (with an English or French version) were retrieved, covering thirteen OECD countries, six Canadian Provinces and the WHO. ANALYSIS: Content analysis was performed based on the categories (differentiation, integration, governance) and sub-categories of the aforementioned conceptual framework. Eight policies that together cover the variations encountered between all policies were used to identify typical configurations. RESULTS: A conceptual framework derived from Parsons' Theory of Social Action posits that social action systems must exhibit a level of internal differentiation that corresponds to the heterogeneity of their external environment and also a level of integration that allows them to remain coherent despite the complexity of their environment. Governance mechanisms help them maintain an equilibrium between differentiation and integration.In terms of differentiation, mental health policies exhibit much variation between the needs and the groups that are prioritized (age, gender, ethnicity, culture, etc.), the types of interventions that are proposed (promotion, prevention, treatment, rehabilitation, etc.), the systemic levels at which interventions take place (society, government as a whole, health care system, organizations, programs, individuals), and the level of specification and scientific basis of proposed interventions. In terms of integration, policies promote various mechanisms belonging to four general categories of increasing effectiveness from hierarchical separation of mandates, to exchange of information, to collaborative planning, and to complete structural integration and co-localisation of certain components (ex. dependence and mental health services). In terms of governance, policies present program theories of varying explicitness and scientific bases, and with different emphases on structures, processes or outcomes. Management models also vary in terms of precision, accountability, financing mechanisms, information systems, and the importance of clinical governance and quality improvement.Five configurations of mental health policies are identified (the public health, the professional, the structural technocratic, the functional technocratic, and the political), each comprising typical combinations of the preceding ingredients. CONCLUSION: The current Quebec mental health policy belongs to the structural technocratic configuration. It specifies fragmented mental health structures with mild integration mechanisms. In the future, it should consider improving its public health aspects (inter-sector work on the determinants of mental health), professional aspects (emphasis on scientific evidence, clinical governance and quality), and functional aspects (integrated specialized community mental health and addiction services). But political factors may prevent it from doing so. PMID- 25120116 TI - [Reflections and recommendations from Quebec mental health university institutes on the working paper of the provincial forum for the 2014-2020 Mental Health Action Plan]. AB - GOAL: Quebec's three mental health university institutes (DMHUI, IUSMM and the IUSMQ) and the Centre hospitalier universitaire de Sherbrooke submitted a statement to the provincial consultation forum on the 2014-2020 Mental Health Action Plan (MHAP), which was held in January 2014 and organized by the Ministere de la Sante et des Services sociaux (MSSS). This article presents these institutes' main recommendations. METHOD: Mental health university institutes deliver a wide and diverse range of services. They know about the challenges of organizing mental health services and are aware of national and international trends in the delivery of the best organizational and clinical practices in mental health. It is therefore as key stakeholders in the mental health care network that they commented on each component in the working paper. RESULTS: The proposed orientations are consistent with the 2005-2010 MHAP. The presented themes clearly reflect current issues, although the guidelines must be more explicit regarding the vision of how services will be organized in coming years. These institutes therefore suggest that the following principles be included: the full exercise of citizenship rights, the organization of services within integrated networks, performance, continuous improvement and innovation, as well as a global and integrated vision of health. The complexity of today's problems requires flexibility, complementarity and continuity of services, particularly for youth, aboriginals, and people with concomitant disorders. These institutions therefore stress the importance of prevention, early intervention programs, and increased support for first-line general practitioners and health care professionals. They also emphasized that specialized inpatient and outpatient services should not be neglected. Community services must also be structured around various levels of support, such as ICM and ACT, as well as around specialized programs available in hospital outpatient clinics. The development and transfer of knowledge remain a central issue when it comes to improving the mental health of the general population. The consolidation of ultra-specialized services, teaching and research should be included in the next MHAP. Finally, a global health perspective must go beyond the MSSS framework to become a governmental and interministerial commitment based on a vision of public mental health that incorporates the health status of the general population and accounts for social determinants. CONCLUSION: It is important to have a national plan that promotes a vision. This plan must be part of an interministerial action plan that truly supports the full exercise of citizenship rights and the fight against stigmatization in collaboration with people who use these services and their families. PMID- 25120117 TI - [Youth mental health at the cross roads of service organization]. AB - The importance of children and youth mental health is increasingly recognized. This rapidly developing field cannot be conceptualized as an extension of adult services to a younger age group and its developmental and organizational specificities are the object of debate. Reviewing recent literature in this domain and some preliminary information about the Quebec Mental Health Plan implementation, this paper addresses some of the questions which structure this debate in Quebec.Quebec mental health plan has put at the forefront collaboration among disciplines and partnership among institutions. In spite of having produced significant improvement in the field, discontinuities in services, which interfere with an ecosystemic model of care, persist. Recent studies suggest that the organisational climate which surrounds youth mental health services has a direct impact on the quality of services and on youth health outcomes. A flexible management structure, which engages clinicians and health workers, favors empowerment, minimizes work stress and facilitates partnership, is needed to foster successful interdisciplinary and intersectorial collaboration. This collaboration is the cornerstone of youth mental health services. PMID- 25120118 TI - [The role of the mental health community in an evolving mental health system. State of knowledge and recommendations]. AB - OBJECTIVES: The objectives of this article are: 1) to trace the history and role of mental health community organizations (MHCO) in the Quebec mental health system as well as their specific values and practices; and 2) to examine the impact of the Quebec Mental Health Plan 2005-2010 on the functioning of community organizations and their relations with the public healthcare system. METHODS: This article draws upon writings produced by the principal provincial and regional community organization associations in Quebec, as well as results of previous studies related to inter-organizational relations among MHCO. RESULTS: The Quebec community-based system consists of several successive generations of the MHCO, each constructed within a particular context. Before 1960, the Canadian Mental Health Association offered activities for promotion and prevention in mental health and participated in the development of several MHCO. The 1970s witnessed the formation of groups aimed at the protection of human rights and the first alternative resources. During the 1980s and 90s, a proliferation of MHCO followed upon their formal recognition by the Ministere de la Sante et des services sociaux (MSSS). These new organizations were established not so much in opposition, or as an alternative, to the public mental health system, but in complement with it. By 2012-13, there were 412 MCHO financed by the MSSS offering services to the population. Roughly half were located in the regions of Montreal, Monteregie and the Capitale Nationale. The MHCO are distinguished from public institutions by a number of characteristics: 1) treatment based not on diagnosis but on the overall situation of the person; 2) shared experience with peers; and 3) empowerment, inviting the person to become involved in decisions concerning his/her treatment and service use as well as decisions that concern the functioning of the organization; 4) establishment of more egalitarian relationships between service users and treating professionals; and 5) rootedness of the organization within the community. MCHO are grouped at the provincial level according to their functions, their ideological affinity, and or their particular mandate, but there is no national classification of community organizations as yet. The financing of community organizations remains a principal source of discontent. The MSSS has indicated that the overall financing of MCHO should correspond to at least 10% of global expenditures for mental health programming, whereas the actual budget is equivalent to only 8.8%. This underfunding obliges community organizations to reduce services despite demands for increased financial assistance, which runs the risk of provoking increased "revolving door" situations, and the utilization of emergency services in cases of service users transferred from hospitals to the Health Social Services Centers, who are in difficulty after losing contact with their service providers who would otherwise have provided follow-up. As well, MCHO fear the loss of their autonomy and of being reduced to the role of secondary services in signing these service agreements. The current reform would represent a step backward for MHCO in terms of recognition of their expertise. The former consultation structures have been dispossessed of any real power, decision making now being in the hands of the regional agency and directors of institutions. Numerous relocations of personnel have also lead to breaks in contact between MCHO and the public system, as these relationships were usually informal. CONCLUSIONS: A number of recommendations emanate from these findings that may permit MHCO to respond more adequately to the needs of the population served without calling into question their autonomy: 1) offer more adequate financing, particularly for self-help groups and organizations offering psychosocial rehabilitation, access to education and work reintegration; 2) allocate specific services exclusively to the community-based system in order to avoid duplication in services; 3) recognize a multiplicity of approaches; and 4) reconstruct appropriate decision making structures. PMID- 25120119 TI - [Advanced nursing practice: a must for the quality of care and mental health services]. AB - New professional legislation and reorganization of mental health services have had a significant influence on mental health nursing practice. Many nurses have demonstrated clinical leadership and have been able to adapt their services to the needs of the population specially in the primary health care setting. However, many believe that the role of nurses is not sufficiently known and optimally utilized in mental health services. In this article we take a critical look at the mental health nursing practice in Quebec and at the essential requirements for its development. This review aims to: 1) describe current trends in the changing roles and the modernization of mental health nursing practice in Quebec, 2) provide an overview of the development of advanced nursing practice and its impact on the quality of mental health services; 3) clarify the concept of advanced nursing practice and position its development in Quebec and 4) propose various strategies for optimizing the role of nurses and their complementarity with other professionals providing mental health services. This review presents innovative practices developed by nurses in the context of the restructuring of mental health services. For example, new nursing roles have been developed to improve the collaboration with general practitioners groups in primary care settings and facilitate the evaluation and monitoring of patient presenting medical and psychological problems. Another interesting innovation was set up by nurses in developing a new service to allow timely access to integrated care for patients with substance abuse and mental health problems. The various testimonies reported in this article illustrate the potential contribution of these nursing innovations in improving the mental health services in Quebec. Also, in few countries, the reform of mental health services has been a good time to recognize this potential. Thus, some countries have repositioned the role of mental health nurses and supported the development of new models of advanced practice in mental health. These developments have been particularly significant in the United States and Australia. In United States, during the 1990s, at least four models of advanced practice in mental health nursing have been developed leading to wide variations in the roles, education, job titles, scope of practice and legal authorizations. Consequently, a consensus model of uniform standards of practice, accreditation and education has been proposed. This LACE model (Licensure, Accreditation, Certification, Education) will be in effect in 2015. Australia has adopted a more systematic approach, unified and progressive to facilitate the development of advanced mental health nursing practice. Australia who, through their many publications, retains more attention since a clear definition of the role of the nurse practitioner in mental health and a legal framework has been adopted at the national level. The Australian experience and the finding from studies suggest that mental health nurse practitioners and nurses who are specialized in mental health have the potential to make a significant contribution to enhancing access to and quality of mental health care through flexible an innovative approaches. So there are more and more evidence and indications that Quebec should invest in enhancing the skills of mental health nurses through the development of advanced nursing practice and integration of this new model in primary care. In addition, researches, funded by the Canadian Services Research Foundation (CHSRF, 2010), shows that the contribution of advanced nursing practice has never been stronger and there is a broad consensus to its value for the Canadian health care system (Dicenso.et Lukosius-Briant, 2010). The implementation of advanced practice nursing role in mental health is part of best practices required to improve care and mental health services and should be taken into account in future Action Plan 2014-2020. PMID- 25120120 TI - [The role of families in the Quebec mental health system]. AB - Purpose. This paper aims to summarize the current situation regarding the role of families of persons with mental disorders within the mental health system in Quebec.Methods. We made a research in the most recent and pertinent papers or books regarding: 1) the history of the family involvement in the mental health system in Quebec; 2) the present situation of these families and the models that we can see and 3) identify in recent governmental or research documents recommendations regarding a greater empowerment of the families in the mental health system.Results. The research provides a historical perspective to the roles occupied by families. First the family was described as a causal agent; the work of the psychoanalyst Freud described the family unit as a source of conflicts in the areas of affect and sexual dynamics, and which results in the appearance of psychiatric symptoms. Later, this view of a causal agent came both from the point of view of genetic and from expressed emotions. In the 70's new perspectives such as general systems theory (von Bertalanffy, 1968), described the family as responsive to mental disorder of one of its members rather than a responsible agent. With the deinstitutionalization movement, the family was perceived as a source of solutions for persons with mental illness, but also as persons who can live some burden. This subject became well described and a several studies reported about adverse effects of caring for a person with mental disorder on the health, well-being and feeling of caregiver burden. In the 90's, some government action plans called for the relationship between the family and the health system as a partnership. Also, families want to be involved in decisions about care and to be informed about the diagnosis and treatment options. ( Lefley et Wasow, 1993)A new model developed by FFAPAMM that identifies three main roles enables to contextualize the current role in the current system. This model, called CAP lists and describes three roles of families that, if they are dependent on the past, continue to mingle in our time. These roles are:Accompanist: the role imposed by being near a person with mental illness (Fradet, 2012). As an accompanist, the family needs to establish relationships with health professionals. Accompanists want to be considered by stakeholders and be respected in their desire to share information and participate in decisions.Client: this is the role that derives from the accompanist when the caregiver receives care services for its psychological or physical problems related to the fact support a sick person.Partner: it is relative to the involvement (or not) the role of family members in the organization of care. It is a role of participation and decision-making. In this context, we also speak of participation in the consultation mechanisms.Recommendations from a Quebec research project and a report of the Commission on Mental Health of Canada will consider a future where the needs and aspirations of families will be taken into account in mental health general services, short term health care, community mental health services. There are also some guidelines regarding education for professionals about the needs of families and about changing politics.Conclusion. There exists in all associations of families of person with mental disorders, training on topics such as how to behave towards different mental disorders or aggressiveness near reached. A project of the Douglas Institute has hired a family member to the emergency room to help families better manage this often difficult time and to facilitate communication with stakeholders. Another project called "Learning to come closer without aggression" has helped more than 200 family members undergo training inspired by the Omega approach, which helps them better manage their own behavior in situations of aggression with their loved one. PMID- 25120122 TI - [Mental health services in Australia]. AB - Canada is 1.5 times the size of Australia. Australia's population of 20 million is located principally on the east coast. Like Canada, the Australia has a federal system of Government with 5 States and two territories. Each State and territory has its own legislation on mental health. The federal (Commonwealth) Government is responsible for health care planning. In addition, the federal Government subsidizes an insurance program (Medicare) that covers visits to specialists and family physicians, while provincial governments are involved in the provision of hospital care and community mental health services. The Commonwealth government also subsidises the cost of medication through the Pharmaceutical Benefits Scheme. These funds are supplemented by private health insurance. Mental health costs account for 6.5 per cent of all health care costs. Primary care treats the majority of common psychological disorders such as anxiety or depression, while specialist mental health services concentrate on those with severe mental illness. There have been 4 national mental health plans since 1992 with the long term aims of promoting mental health, increasing the quality and responsiveness of services, and creating a consistent approach to mental health service system reform among Australian states and territories. These systematic cycles of planning have first allowed a shift from psychiatric hospitals to community services, from reliance on psychiatric hospitals as pivotal to psychiatric care system. Community care budgets have increased, but overall have decreased with money not following patients; but recent deployment of federally funded through Medicare access to psychotherapy by psychologists for common mental disorders in primary care have increased overall budget. Concerns remain that shift to youth first onset psychosis clinics may come from older long term psychotic patients, a form of discrimination whilst evidence amount of excess mortality by cardio-vascular diseases and cancers, and due to poverty, poor health prevention and primary health care for these patients. From a system perspective, Australia has been inspired by Canada and created in 2012 its own mental health commission with a similar leading role for patients and families, aboriginal people representatives, but also a surveillance of the system with its own yearly report, like the Quebec Health Commissioner 2012 mental health system performance report. PMID- 25120121 TI - [Public participation and civic participation of service users in relation to the Mental Health Action Plan 2005-2010: their spokesperson function]. AB - CONTEXT: Among the guiding principles of the Mental Health Action Plan 2005-2010 (MHAP) of the Quebec Ministere de la sante et des services sociaux (Health and Social Services) is the recognition that persons who use mental health services (consumers) can be active agents of their own individual and collective recovery journey. In accordance with this principle, the MHAP called for greater participation of consumers in local, regional and national decision-making bodies within the network of health and social services in Quebec. OBJECTIVE: The objectives of this article are to look back on the various forms of consumers' participation in connection with the MHAP since its enactment, and to better understand the complexities of being spokespersons through the Actor Network Theory conceptual framework. METHOD: A scientific literature review was conducted. Different angles of analysis were used to highlight convergences and trends based on official governmental publications and ongoing research on consumers' participation in decision and policy making. It was thought that a vertical case study approach would offer an historical perspective going back to the early 1960s to discuss the foundations of an "ideology of participation." Another way of assessing participation is through a horizontal approach that would compare the terms of participation implemented from one regional authority to the other, in order to cover most of the Quebec territory. RESULTS: The MHAP did not provide clear indicators of how to assess progress made with regards to greater consumer participation. In some regions of Quebec, this participation was coordinated by community organizations that designated their representatives. In other regions, local authorities included consumers on a more individual basis to give their opinion. As all were not at the same stage in their recovery process, some were in a position to speak using the "we," while others still needed to express themselves using the "I." In either case, their function as spokespersons proved to be a bi-directional function. In one direction, the spokesperson informed the governmental and institutional stakeholders about the expectations of consumers and about their daily life realities. In the other way, they were able to explain and make more intelligible the intricacies of the system with a lay language, which helped non specialists they encountered to remain informed partners, even though indirectly. As they shared their experience as spokespersons with their peers, their peers were able to get a clearer understanding of the progress made to effectively promote active and effective participation. The lack of clear expectations and dedicated means to support participation, induced discrepancies from one region to another, making it difficult, though, to assess progress made overall. CONCLUSION: As the function of spokesperson got more professionalized with increased opportunities to participate in policy and decision-making, spokespersons spoke from an "us" rather than an "I" standpoint. The concept of public participation evolved to one of civic participation, with the possibility to transcend the "us" and "them" dichotomy, as members of a community are all citizens to one another. Still, the terms and conditions of participation could be better defined and more predictable for greater equity in terms of access to different levels of policy and decision-making. PMID- 25120123 TI - [A global reform of mental health care based on a community approach: the Belgian experience]. AB - The developments in mental health care in Belgium over the last few years show that some major steps are already taken towards implementing community oriented care. In Belgium, we are going through a historic moment, as the proposed reform is ambitious but also complex. Indeed we talk here about a comprehensive mental health care reform which brings together federal, regional and community competencies.It aims to transform part of hospital care into community oriented care by e.g. creating mobile teams in the existing community care mechanisms.In the same time we are developing an operational approach to networking focusing on the needs of care users and of their families.In this paper, we will describe the content of the reform, its mechanisms and all care professionals involved. We will also present the progress of the exploratory phase by stressing not only positive aspects that highlight the evolving nature of our approach, but also the difficulties we are facing in implementing it. PMID- 25120124 TI - [The effect of age, gender and socioeconomic status on the use of services for psychological distress symptoms in the general medical sector: Results from the ESA research program on mental health and aging]. AB - OBJECTIVES: The objective of this study was, first, to document the psychometric characteristics of a measure of the older adults' socioeconomic status and, secondly, to test the effect of the socioeconomic status on the association between the older adults perceived need to improve their mental health and their use of services in the general medical sector for psychological distress symptoms taking into account the effect of age and gender. METHOD: Data used in this study come from the ESA study (Enquete sur la sante des aines) on mental health and aging, conducted in 2005-2008 using a probabilistic sample (n=2811) of the older adult population aged 65 years and over living at home in Quebec. RESULTS: Our results showed that a measurement model of the older adults' socioeconomic status including an individual-level (SES_I) and an area/contextual-level dimension of socioeconomic deprivation (SES_C) was plausible. The reliability of the SES index used in the ESA research program was .92. Our results showed that women (b=-.43) and older people (b=-.16) were more at risk to have a disadvantaged socioeconomic status. However, our results did not show evidence of a significant association between the older adults' socioeconomic status, their perception of a need to improve their mental health and the use of medical services for psychological distress symptoms in the general medical sector in the older adult population in Quebec. CONCLUSION: Our results do not support the idea suggested in other studies that socioeconomic status has an effect on the older adults use of services for psychological distress symptoms in the general medical sector and suggest that in a context where medical health services are provided under a public insurance programme context, the socioeconomic status does not influence access to services in the general medical sector in the older adult population. PMID- 25120126 TI - [Evaluating the implementation of involuntary hospitalization procedures: a profile of people, audits and recommendations]. AB - Since the 1990s, legislative reforms have been undertaken in many Western countries to reduce involuntary hospitalization. Studies examining fluctuation rates before and after the legislative reform show a general trend toward an increase rather than a decrease in involuntary hospitalization rates (de Stefano & Ducci, 2008). In Quebec, many reports have shown that consent for psychiatric evaluation and hospitalisation for people who present an imminent danger to themselves or to others is difficult to obtain due to clinical, legal, and ethical considerations. To facilitate this process, a new protocol was developed and implemented following the training of 335 health workers and 85 medical doctors in 6 hospitals. Our study evaluated this protocol and established a profile of people who had been hospitalized against their will. Using a retrospective analysis, we examined the files of 179 patients who underwent a psychiatric evaluation process during an involuntary hospitalization. This file analysis allowed us to develop a better profile of these people and determine whether the required forms were present and how adequately they were filled out by the professionals. We also conducted a study with the professionals responsible for applying the new protocol to get a better idea of its characteristics (relative advantage, compatibility, simplicity, reversibility and observability) as well as the principles of consent and the obstacles to its implementation.Our study showed that that half of the patients were diagnosed with schizophrenia or another psychosis. Fifty-four point two percent (54.2%) of the patients were males, 79% were single or separated and only 18,4% were working. At the time of their crisis situation, 30,7% were brought to the hospital by police officers and 19% were already hospitalized. The remaining patients were brought in by ambulance, family members or they came in by themselves. Professional opinion of the new protocol was positive however they did not rigorously enter the data required in the new forms. The new form was present in only 51% of files and when consent was given, it was only documented in 27% of the cases.These results highlight the need to improve the documentation process given in the protocol. It would be very useful to establish strategies to obtain this consent in light of the specific characteristics that make up this subgroup of people who have been hospitalized against their will. Legislation alone is not enough to invoke a change in the involuntary hospitalisation rate. The clinical and organisational context must also be actively prepared to receive this new practice. In order to do this, evaluative research could contribute to improving the level of implementation and be of benefit to people in crisis and those with mental disorders. PMID- 25120125 TI - [Attitudes of general physicians and family medicine residents towards patients with borderline personality disorder]. AB - OBJECTIVES: Several studies suggest that health professionals show negative attitudes towards people with Borderline Personality Disorder (BPD). Many publications have focused on the attitudes of nurses or other type of clinicians like social workers or psychologists. Few researches concern the attitudes of general physicians towards BPD even if they are the main professionals involved in the evaluation and treatment of these patients. Additionally, patients with BPD frequently consult general physicians and, because of the difficulties interacting with these patients, they do not always receive the treatments required by their condition. This research aims to assess the attitudes of general physicians and family medicine residents regarding patients presenting with this disorder. METHOD: Forty family medicine residents and thirty-five general physicians were compared to thirty-nine mental health professionals using the Attitudes toward people with BPD Scale (ABPDS; Bouchard, 2001). This measure has two subscales labeled Comfort when interacting with someone who has BPD and Positives perceptions about BPD. The internal consistency of the scale as well as the two distinct factors are satisfactory. The participants also complete a socio demographic questionnaire. Means, t tests, ANOVAs and factorial ANOVAs are completed in order to compare the three groups on the ABPDS and explore the influence of variables such as sex, age, years of experience, and professional setting (urban or rural) on the results. RESULTS: The results show that general physicians have similar attitudes than mental health professionals towards people presenting with BPD and that family medicine residents present less positive attitude than the other two groups. In addition, clinicians with less experience tend to have less positive attitudes towards people with BPD and clinicians from urban settings seem to have more positive attitude. It was difficult to determinate which variables influence the results because the years of experience, the professional settings and the title of the participants are extremely related. The factorial ANOVAs show no interaction effect between these three variables. CONCLUSION: Several studies show that health professionals present negative attitudes toward patients with BPD. This study reveals that general physicians and family medicine residents show respectively similar attitudes or less positive attitudes than other mental health professionals. These results underline the importance of providing specific training about BPD to family medicine residents. Because general physicians guide the evaluations and interventions concerning these patients and mental health professionals interact regularly with BPD, it will be helpful if all the clinicians receive more specific training regarding this disorder. PMID- 25120127 TI - [For us, being full citizens means...]. AB - OBJECTIVE: One of the four main chapters of the consultation document proposed by the Quebec Ministere de la sante et des services sociaux (Health and Social Services), in preparation for the National Forum on the Mental Health Action Plan 2014-2020, is dedicated to the full exercise of citizenship. This paper reports the dialogue that took place between the CEO of a university mental health institute and a group of service users, in order to participate in the consultation process regarding the full exercise of citizenship. METHOD: Since May 2013, a dozen service users have gathered in the Projet citoyen at the Research Centre of Institut universitaire en sante mentale de Montreal (IUSMM). The Projet citoyen is a culturally adapted transposition, in Quebec, of the Citizens Project that is in place in New Haven, Connecticut. One of the key components of both the Projet citoyen and the Citizens Project interventions is a group training regarding citizenship. Participants discuss what it means for them to be full citizens and they support each other in achieving personal or collective goals. To assess progress made in such matters, a new Citizenship Measurement has been developed by the Yale Program for Recovery & Community Health, and translated into French. This Mesure de la citoyennete is in the process of being validated; peer research assistants conducted data collection by asking 178 people who use the mental health services of Quebec to complete the French Mesure de la citoyennete. The preliminary results of a statistical analysis were used to structure the dialogue between the IUSMM CEO and the participants of the Projet citoyen. RESULTS: Three sub-scales emerged from preliminary statistical analysis (clusters). Colleagues of the Projet citoyen were invited, through a focus group conducted by one of them, to give evocative labels to these sub-scales. Regarding the first one, we felt that it was about asking ourselves what we can bring to others' lives, wondering how we, as members of the community, can make a difference for a more inclusive civic cohabitation. The label "contribution to the community" was chosen. For the second sub-scale, personal and social spheres emerged as both being essential to the achievement of full citizenship. These spheres must be respected in complementarity. Hence we chose the label: "personal and social integrity." Finally, the third sub-scale seemed to combine items that have the common elements of respecting human rights, respecting the person, and respecting the autonomy of the person. "Rights and freedom of choice" was chosen as a label for that sub-set. The IUSMM CEO immersed herself in the Projet citoyen and as her dialogue with the participants deepened around these features, a sense of mutual respect and friendliness got stronger. Participants were pleasantly surprised to see that an influential CEO can be sensitive and comfortable expressing this sensitivity, even with her emotions while interacting with service users as they are exercising their own citizenship as research colleagues. CONCLUSION: This case study illustrates a way of triangulating qualitative and quantitative data sets generated from a participatory-action research project for which people who use mental health services have been active research partners throughout. A mobilizing effect was found among participants of the Projet citoyen who become multipliers once back in their respective communities and neighborhoods. This effect can also affect a senior manager. The ISUMM CEO was inspired to relay and communicate this innovative thinking on the full exercise of citizenship as a governmental priority in mental health. It could thus be recommended to implement and network some Projets citoyens in other educational, research and clinical settings. This would provide opportunities for service users to contribute to the community - here, the scientific community. It would exemplify respect for personal and social integrity by channeling the expression of the lived experience into an instrument of change. These Projets citoyens would advocate for the rights and freedom of choice of service users as partners, in action, of a citizenship oriented mental health system. PMID- 25120129 TI - On the formation of the porous structure in nanostructured a-Si coatings deposited by dc magnetron sputtering at oblique angles. AB - The formation of the porous structure in dc magnetron sputtered amorphous silicon thin films at low temperatures is studied when using helium and/or argon as the processing gas. In each case, a-Si thin films were simultaneously grown at two different locations in the reactor which led to the assembly of different porous structures. The set of four fabricated samples has been analyzed at the microstructural level to elucidate the characteristics of the porous structure under the different deposition conditions. With the help of a growth model, we conclude that the chemical nature of the sputter gas not only affects the sputtering mechanism of Si atoms from the target and their subsequent transport in the gaseous/plasma phase towards the film, but also the pore formation mechanism and dynamics. When Ar is used, pores emerge as a direct result of the shadowing processes of Si atoms, in agreement with Thornton's structure zone model. The introduction of He produces, in addition to the shadowing effects, a new process where a degree of mobility results in the coarsening of small pores. Our results also highlight the influence of the composition of sputtering gas and tilt angles (for oblique angle deposition) on the formation of open and/or occluded porosity. PMID- 25120128 TI - Systemic oxygenation weakens the hypoxia and hypoxia inducible factor 1alpha dependent and extracellular adenosine-mediated tumor protection. AB - Intratumoral hypoxia and hypoxia inducible factor-1alpha (HIF-1-alpha)-dependent CD39/CD73 ectoenzymes may govern the accumulation of tumor-protecting extracellular adenosine and signaling through A2A adenosine receptors (A2AR) in tumor microenvironments (TME). Here, we explored the conceptually novel motivation to use supplemental oxygen as a treatment to inhibit the hypoxia/HIF 1alpha-CD39/CD73-driven accumulation of extracellular adenosine in the TME in order to weaken the tumor protection. We report that hyperoxic breathing (60 % O2) decreased the TME hypoxia, as well as levels of HIF-1alpha and downstream target proteins of HIF-1alpha in the TME according to proteomic studies in mice. Importantly, oxygenation also downregulated the expression of adenosine generating ectoenzymes and significantly lowered levels of tumor-protecting extracellular adenosine in the TME. Using supplemental oxygen as a tool in studies of the TME, we also identified FHL-1 as a potentially useful marker for the conversion of hypoxic into normoxic TME. Hyperoxic breathing resulted in the upregulation of antigen-presenting MHC class I molecules on tumor cells and in the better recognition and increased susceptibility to killing by tumor-reactive cytotoxic T cells. Therapeutic breathing of 60 % oxygen resulted in the significant inhibition of growth of established B16.F10 melanoma tumors and prolonged survival of mice. Taken together, the data presented here provide proof of principle for the therapeutic potential of systemic oxygenation to convert the hypoxic, adenosine-rich and tumor-protecting TME into a normoxic and extracellular adenosine-poor TME that, in turn, may facilitate tumor regression. We propose to explore the combination of supplemental oxygen with existing immunotherapies of cancer. KEY MESSAGES: Oxygenation decreases levels of tumor protecting hypoxia. Oxygenation decreases levels of tumor protecting extracellular adenosine. Oxygenation decreases expression of HIF-1alpha dependent tumor-protecting proteins. Oxygenation increases MHC class I expression and enables tumor regression. PMID- 25120130 TI - Closed-tube human leukocyte antigen DQA1*05 genotyping assay based on switchable lanthanide luminescence probes. AB - Genotyping in closed tube is commonly performed using polymerase chain reaction (PCR) amplification and allele-specific oligonucleotide probes using fluorescence resonance energy transfer (FRET). Here we introduce a homogeneous human leukocyte antigen (HLA)-DQA1*05 end-point PCR assay based on switchable lanthanide luminescence probe technology and a simple dried blood sample preparation. The switchable probe technology is based on two non-luminescent oligonucleotide probes: one carrying a non-luminescent lanthanide chelate and the other carrying a light-absorbing antenna ligand. Hybridization of the probes in adjacent positions to the target DNA leads to the formation of a highly luminescent lanthanide chelate complex by self-assembly of the reporter molecules. Performance of the HLA-DQA1*05 assay was evaluated by testing blood samples collected on sample collection cards and was prepared by lysing the punched samples (3-mm discs) using alkaline reaction conditions and high temperature. Testing of 147 blood samples yielded 100% correlation to the heterogeneous DELFIA technology-based reference assay. Genotyping requires carefully designed probe sequences able to discriminate matched and mismatched target sequences by hybridization. Furthermore, definite genotype discrimination was achieved because inherently non-luminescent switchable probes together with time-resolved measurement mode led to very low background signal level and, therefore, very high signal differences averaging 54-fold between DQA1*05 and other alleles. PMID- 25120131 TI - Combining stress-only myocardial perfusion imaging with coronary calcium scanning as a new paradigm for initial patient work-up: an exploratory analysis. AB - BACKGROUND: We conducted an exploratory analysis to test whether the addition of a CAC scan can increase the applicability of stress-only SPECT-MPI. METHODS: We studied 162 patients referred for rest/stress SPECT-MPI who underwent a CAC scan. Each scan was interpreted by two readers in stepwise fashion: stress-only images; addition of clinical data; and addition of CAC data. At each step, the reader was asked if rest SPECT-MPI was necessary. RESULTS: Stress-only images were interpreted as normal in 62, probably normal in 42, equivocal in 15, probably abnormal in 5, and definitely abnormal in 38 patients. Rest SPECT-MPI imaging was considered necessary, in 0% of normal studies, but in 88% of probably normal studies, and 100% of those with equivocal/abnormal studies. Addition of the clinical data did not materially change this decision. Additional consideration of the CAC scan results did not influence the deemed lack of need for a rest SPECT-MPI with normal SPECT-MPI or the necessity of rest SPECT-MPI with abnormal SPECT-MPI. However, the CAC scan reduced the deemed need for a rest SPECT-MPI in 72% with a probably normal, 47% with an equivocal, and 40% of those with a probably abnormal SPECT-MPI. CONCLUSIONS: Our exploratory analysis indicates that addition of a CAC scan to stress SPECT-MPI tends to diminish experienced readers' deemed need to perform rest SPECT-MPI studies among patients with probably normal or borderline stress-only SPECT-MPI studies. Thus, further study appears warranted to assess the utility of using CAC scanning as a means for increasing the percent of SPECT-MPI studies that can be performed as stress-only studies. PMID- 25120133 TI - Phase analysis of myocardial SPECT to understand mechanisms of disease and therapy. PMID- 25120134 TI - Are absolute myocardial blood flow PET measurements ready for clinical use? PMID- 25120132 TI - Data-driven respiratory motion tracking and compensation in CZT cameras: a comprehensive analysis of phantom and human images. AB - BACKGROUND: This study described a method for tracking and compensating respiratory motion in cadmium-zinc-telluride (CZT) cameras. We evaluated motion effects on myocardial perfusion imaging and assessed the usefulness of motion compensation in phantom and clinical studies. METHODS: SPECT studies were obtained from an oscillating heart phantom and 552 patients using CZT cameras with list-mode acquisition. Images were reformatted in 500-ms frames, and the activity centroid was calculated as respiratory signal. The myocardial perfusion, left ventricular (LV) wall thickness, and LV volume were assessed before and after the motion compensation technique. RESULTS: In phantom studies, we documented only minimal bias between simulated and measured shifts. Significantly reduced tracer activity, increased wall thickness and decreased volume in scans with 15 mm or more axial shifts were noted. In clinical studies, there was a higher prevalence of significant motion after treadmill exercise. The motion compensation technique could successfully compensate those motion artifacts. CONCLUSION: The described method allows for tracking and compensating respiratory motion in CZT cameras. Significant respiratory motion is still not uncommon using CZT cameras, especially in patients who underwent treadmill tests. Motion blurring can be compensated using image processing techniques and image quality could be significantly improved. PMID- 25120136 TI - Training in time-limited dynamic psychotherapy: A systematic comparison of pre- and post-training cases treated by one therapist. AB - OBJECTIVE: This qualitative study systematically compared cases treated by the same therapist in order to understand the group comparison findings of a larger study on training of experienced therapists (the "Vanderbilt II" psychotherapy project). METHOD: The therapist, Dr C., was selected based on the therapist's overall treatment successes. His two patients were selected based on their outcomes and the relative training cohort from which they were drawn: a case with successful outcome from the pre-training cohort and a case of negligible improvement from the post-training cohort. RESULTS: Dr C. demonstrated a variety of interpersonal skills throughout his pre-training case, though there was also poor interpersonal process throughout. However, in the second case he had considerable difficulty in adapting his typical therapeutic approach to the requirements of the time-limited dynamic psychotherapy (TLDP) manual, even while appearing to work hard to find ways to use the manual. CONCLUSIONS: Dr C.'s spontaneity, and his unique set of interpersonal skills may enhanced his initial rapport and alliance building with clients and yet may not have interfaced well with TLDP. His unique interpersonal skills also may have contributed to problems of interpersonal process. Future research may benefit from examining the interaction of between therapist interpersonal skills and the implementation of the treatment manual. PMID- 25120138 TI - Chemical-assisted femtosecond laser writing of lab-in-fibers. AB - The lab-on-chip (LOC) platform has presented a powerful opportunity to improve functionalization, parallelization, and miniaturization on planar or multilevel geometries that has not been possible with fiber optic technology. A migration of such LOC devices into the optical fiber platform would therefore open the revolutionary prospect of creating novel lab-in-fiber (LIF) systems on the basis of an efficient optical transport highway for multifunctional sensing. For the LIF, the core optical waveguide inherently offers a facile means to interconnect numerous types of sensing elements along the optical fiber, presenting a radical opportunity for optimizing the packaging and densification of diverse components in convenient geometries beyond that available with conventional LOCs. In this paper, three-dimensional patterning inside the optical fiber by femtosecond laser writing, together with selective chemical etching, is presented as a powerful tool to form refractive index structures such as optical waveguides and gratings as well as to open buried microfluidic channels and optical resonators inside the flexible and robust glass fiber. In this approach, optically smooth surfaces (~12 nm rms) are introduced for the first time inside the fiber cladding that precisely conform to planar nanograting structures when formed by aberration-free focusing with an oil-immersion lens across the cylindrical fiber wall. This process has enabled optofluidic components to be precisely embedded within the fiber to be probed by either the single-mode fiber core waveguide or the laser formed optical circuits. We establish cladding waveguides, X-couplers, fiber Bragg gratings, microholes, mirrors, optofluidic resonators, and microfluidic reservoirs that define the building blocks for facile interconnection of inline core-waveguide devices with cladding optofluidics. With these components, more advanced, integrated, and multiplexed fiber microsystems are presented demonstrating fluorescence detection, Fabry-Perot interferometric refractometry, and simultaneous sensing of refractive index, temperature, and bending strain. The flexible writing technique and multiplexed sensors described here open powerful prospects to migrate the benefits of LOCs into a more flexible and miniature LIF platform for highly functional and distributed sensing capabilities. The waveguide backbone of the LIF inherently provides an efficient exchange of information, combining sensing data that are attractive in telecom networks, smart catheters for medical procedures, compact sensors for security and defense, shape sensors, and low-cost health care products. PMID- 25120137 TI - Resveratrol attenuates hypoxia/reoxygenation-induced Ca2+ overload by inhibiting the Wnt5a/Frizzled-2 pathway in rat H9c2 cells. AB - Resveratrol is able to protect myocardial cells from ischemia/reperfusion-induced injury. However, the mechanism has yet to be fully elucidated. In the present study, it is reported that resveratrol has a critical role in the control of Ca2+ overload, which is the primary underlying cause of ischemia/reperfusion injury. Hypoxia/reoxygenation (H/R) treatment decreased the cell viability and increased the apoptosis of H9c2 cells, whereas the caspase-3 and intracellular Ca2+ levels were greatly elevated compared with the control group. Treatment of H9c2 cells with resveratrol (5, 15 and 30 uM) reduced caspase-3 expression and cardiomyocyte apoptosis in a dose-dependent manner, and the intracellular Ca2+ overload was also significantly decreased. Furthermore, Frizzled-2 and Wnt5a belong to the non canonical Wnt/Ca2+ pathway, which have been demonstrated to be responsible for Ca2+ overload, and were thus detected in the present study. The results indicated that both the mRNA and protein expression levels of Frizzled-2 and Wnt5a in H/R induced H9c2 cells were markedly increased compared with the levels found in normal cells, and treatment with resveratrol (5, 15 and 30 uM) significantly reduced the expression of Frizzled-2 and Wnt5a compared with the H/R group. The results indicated that resveratrol protected myocardial cells from H/R injury by inhibiting the Ca2+ overload through suppression of the Wnt5a/Frizzled-2 pathway. PMID- 25120135 TI - HIV and Stem Cell Transplantation. AB - In human immunodeficiency virus (HIV)-infected persons, the incidence of hematologic malignancies, including leukemia and lymphoma, is increased despite the use of successful antiretroviral therapy. Hematopoietic stem cell transplantation (SCT) is emerging as a safe and effective therapy for HIV infected persons with hematologic malignancies. Management of these patients is complicated by drug-drug interactions involving antiretroviral therapy (ART) that may impact conditioning agent efficacy and metabolism of immunosuppressive medications and potentiate drug toxicities. As such, optimal strategies for ART remain controversial. We discuss recent advances, controversies, and future directions related to SCT in HIV-infected persons, including the investigation of allogeneic SCT as a strategy for HIV cure. PMID- 25120139 TI - Immunohistological examination of a skin lesion in a Japanese case with hand, foot and mouth disease caused by coxsackie-virus A6. PMID- 25120143 TI - From epidemiology and genetics to diagnostics, outcome measures, and novel treatments in autoimmune bullous diseases. PMID- 25120144 TI - Proteomic revelations. AB - The power of proteomics in cultured skin fibroblasts from individuals with either systemic sclerosis or recessive dystrophic epidermolysis bullosa has led to the common finding of senescence and deficiencies in autophagy. Both of these disorders exert high demand on fibroblast activity, and without the protective action of autophagy cellular stress could have many adverse effects that are further amplified by the senescent phenotype. PMID- 25120145 TI - The virtues of oxygenation: low tissue oxygen adversely affects the killing of Leishmania. AB - Hypoxia contributes to the persistence of infections through altered immune responses. Studies examining skin O2 changes at the site of a lesion are limited. The prevailing methods require the use of electrochemical O2 sensors or radiolabeled electrodes that utilize O2 and may interfere with the precision at low O2 levels. In this issue, Mahnke et al. (2014) demonstrate, using a novel fluorescence-based imaging technology, that low oxygen tension (pO2) impairs NO mediated anti-leishmanial immunity, leading to increased parasite burden. Replenishing tissue oxygen profoundly enhanced NO-mediated leishmanial killing, underscoring the need to accurately assess oxygenation in infected tissues as a novel strategy to challenge intracellular infection. The technology presented here may have clinical-translational potential in noninvasively assessing disease burden and response to treatment. PMID- 25120146 TI - A new player on the psoriasis block: IL-17A- and IL-22-producing innate lymphoid cells. AB - Innate lymphoid cells (ILCs) are a recently discovered family of innate immune cells belonging to the lymphoid lineage, yet lacking antigen-specific receptors. ILCs were first identified in the intestinal tract, where they contribute to epithelial barrier integrity and host responses to commensal microbes. Teunissen et al. (in the current issue) and Villanova et al. (2014) now suggest an important role for type 3 ILCs (ILC3s) in the skin, particularly in psoriasis. Both groups found an increased frequency of IL-22- and/or IL-17A-producing ILCs in psoriatic skin and blood. These cells are activated in response to IL-1beta and IL-23, correlate with disease severity, and are decreased following antitumor necrosis factor-alpha (anti-TNFalpha) treatment. The presence of a novel ILC population in psoriatic skin, one that responds to biologic therapeutics, suggests that dysregulation of ILCs is a contributing factor to psoriasis pathogenesis. PMID- 25120147 TI - Gene regulation at a distance: higher-order chromatin folding and the coordinated control of gene transcription at the epidermal differentiation complex locus. AB - Chromatin structure and spatial interactions between proximal and distal gene regulatory elements, including gene core promoters and enhancers, are important in the control of gene transcription. In this issue, Oh et al. characterized an AP-1-dependent enhancer at the epidermal differentiation complex locus that establishes spatial interactions with numerous gene promoter regions at that locus. PMID- 25120148 TI - Keratinocyte growth regulation TRP-ed up over downregulated TRPV4? AB - This commentary on an exciting new study (Fusi et al., 2014) puts the finding of TRPV4 downregulation in several nonmelanoma skin cancers into context. The original paper point toward possible use of TRPV4 as dermatopathologic marker, also toward the possibility that downregulated TRPV4 can affect biological properties of the cancer, by enhancing, but also regulating tumor growth. As calcium-permeable TRPV4 has recently been identified as UVB-receptor in skin keratinocytes, where it regulates skin tissue injury and pain after UVB overexposure, it is discussed whether TRPV4 downregulation can also be found in other non-UVB-exposed cancers. PMID- 25120149 TI - Augmentation of cutaneous wound healing by pharmacologic mobilization of endogenous bone marrow stem cells. AB - Novel therapeutic tools to accelerate wound healing would have a major impact on the overall burden of skin disease. Lin et al. demonstrate in mice that endogenous bone marrow stem cell mobilization, produced by a pharmacologic combination of AMD3100 and tacrolimus, leads to faster and better-quality wound healing, findings that have exciting potential for clinical translation. PMID- 25120150 TI - JID VisualDx Quiz: September 2014. PMID- 25120151 TI - Tissue microarray. PMID- 25120152 TI - Cells to surgery quiz: September 2014. PMID- 25120153 TI - Dental knowledge and attitude toward school dental-health programs among parents of kindergarten children in Winterthur. AB - The current study investigated the attitudes and knowledge regarding diet and oral hygiene of parents with kindergarten children. The parents' statements were evaluated in terms of their socioeconomic background and were compared with the annual clinical examination of the children. The objective of the study was to assess the effectiveness of the school dental-health program and adapt it to today's societal needs. Of those who participated in the interview, 61% were Swiss, 16% were from former Yugoslavia or Turkey, and 12% each from the EU or other countries. Of the children examined, 39% already had caries, and 18% of those showed more than two lesions. The parents' knowledge correlated with the severity of the child's caries as well as with the parents' income, country of origin, and education. There was a correlation between the child's dental decay and lower income, as well as lower education and non-Swiss nationality of the parents. Parents with higher income and better education more often participated in the preschool's preventive program. Parents from former Yugoslavia or Turkey participated less frequently than parents from other countries. The study demonstrated that parents who especially needed instruction and prophylaxis are contacted too late or not at all through the dental-health program at kindergarten and that new approaches to prevention should be implemented to more effectively reach the parents. PMID- 25120154 TI - Women with osteoarthritis have elevated synovial fluid levels of insulin-like growth factor (IGF)-1 and IGF-binding protein-3. AB - The present study explores the possible connection between synovial fluid concentrations of insulin like growth factor (IGF-1), IGF-binding protein (IGFBP 3), leptin, and C-reactive protein (CRP) in osteoarthritis (OA). Synovial fluid specimens were obtained from a total of thirty-four individuals with and without OA. Protein-normalized measurements of IGF-1, IGFBP-3, and leptin concentrations in synovial fluid showed significantly (P < 0.05) elevated levels in women with knee OA but not in men. This study provides initial evidence that protein normalized IGF-1 and IGFBP-3 and leptin levels increase in synovial fluid of women but not in men with OA versus those without OA. PMID- 25120155 TI - Hematologic malignancies of the pancreas. AB - Hematologic malignancies are relatively uncommon neoplasms of abdominal soft tissue. This article discusses the clinical and imaging features of pancreatic lymphoma, pancreatic extraosseous multiple myeloma, granulocytic sarcoma (chloroma), posttransplant lymphoproliferative disorder, and Castleman disease. The combination of imaging findings and the appropriate clinical presentation should allow the radiologist to raise a provisional diagnosis of hematologic malignancy. PMID- 25120156 TI - Studies of hot photoluminescence in plasmonically coupled silicon via variable energy excitation and temperature-dependent spectroscopy. AB - By integrating silicon nanowires (~150 nm diameter, 20 MUm length) with an Omega shaped plasmonic nanocavity, we are able to generate broadband visible luminescence, which is induced by high order hybrid nanocavity-surface plasmon modes. The nature of this super bandgap emission is explored via photoluminescence spectroscopy studies performed with variable laser excitation energies (1.959 to 2.708 eV) and finite difference time domain simulations. Furthermore, temperature-dependent photoluminescence spectroscopy shows that the observed emission corresponds to radiative recombination of unthermalized (hot) carriers as opposed to a resonant Raman process. PMID- 25120157 TI - Development of a PET scanner for simultaneously imaging small animals with MRI and PET. AB - Recently, positron emission tomography (PET) is playing an increasingly important role in the diagnosis and staging of cancer. Combined PET and X-ray computed tomography (PET-CT) scanners are now the modality of choice in cancer treatment planning. More recently, the combination of PET and magnetic resonance imaging (MRI) is being explored in many sites. Combining PET and MRI has presented many challenges since the photo-multiplier tubes (PMT) in PET do not function in high magnetic fields, and conventional PET detectors distort MRI images. Solid state light sensors like avalanche photo-diodes (APDs) and more recently silicon photo multipliers (SiPMs) are much less sensitive to magnetic fields thus easing the compatibility issues. This paper presents the results of a group of Canadian scientists who are developing a PET detector ring which fits inside a high field small animal MRI scanner with the goal of providing simultaneous PET and MRI images of small rodents used in pre-clinical medical research. We discuss the evolution of both the crystal blocks (which detect annihilation photons from positron decay) and the SiPM array performance in the last four years which together combine to deliver significant system performance in terms of speed, energy and timing resolution. PMID- 25120158 TI - Development of an ELISA and immunochromatographic strip for highly sensitive detection of microcystin-LR. AB - A monoclonal antibody for microcystin-leucine-arginine (MC-LR) was produced by cell fusion. The immunogen was synthesized in two steps. First, ovalbumin/ bovine serum albumin was conjugated with 6-acetylthiohexanoic acid using a carbodiimide EDC (1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride)/ NHS (N hydroxysulfosuccinimide) reaction. After dialysis, the protein was reacted with MC-LR based on a free radical reaction under basic solution conditions. The protein conjugate was used for immunization based on low volume. The antibodies were identified by indirect competitive (ic)ELISA and were subjected to tap water and lake water analysis. The concentration causing 50% inhibition of binding of MC-LR (IC50) by the competitive indirect ELISA was 0.27 ng/mL. Cross-reactivity to the MC-RR, MC-YR and MC-WR was good. The tap water and lake water matrices had no effect on the detection limit. The analytical recovery of MC-LR in the water samples in the icELISA was 94%-110%. Based on this antibody, an immunochromatographic biosensor was developed with a cut-off value of 1 ng/mL, which could satisfy the requirement of the World Health Organization for MC-LR detection in drinking water. This biosensor could be therefore be used as a fast screening tool in the field detection of MC-LR. PMID- 25120159 TI - A novel carbon nanofibers grown on glass microballoons immunosensor: a tool for early diagnosis of malaria. AB - This paper presents a novel method for direct detection of Plasmodium falciparum histidine rich protein-2 (PfHRP-2) antigen using carbon nanofiber (CNF) forests grown on glass microballoons (NMBs). Secondary antibodies specific to PfHRP-2 densely attached to the CNFs exhibit extraordinary ability for the detection of minute concentrations of Plasmodium species. A sandwich immunoassay protocol was employed, where a glass substrate was used to immobilize primary antibodies at designated capture zones. High signal amplification was obtained in both colorimetric and electrical measurements due to the CNFs through specific binding. As a result, it was possible to detect PfHRP-2 levels as low as 0.025 ng/mL concentration in phosphate buffered saline (PBS) using a visual signal within only 1 min of test duration. Lower limits of 0.01 ng/mL was obtained by measuring the electrical resistivity of the capture zone. This method is also highly selective and specific in identifying PfHRP-2 and other Plasmodium species from the same solution. In addition, the stability of the labeling mechanism eliminates the false signals generated by the use of dyes in current malaria rapid diagnostic test kits (MRDTs). Thus, the rapid, sensitive and high signal amplification capabilities of NMBs is a promising tool for early diagnosis of malaria and other infectious diseases. PMID- 25120160 TI - A catheter-based acoustic interrogation device for monitoring motility dynamics of the lower esophageal sphincter. AB - This paper presents novel minimally-invasive, catheter-based acoustic interrogation device for monitoring motility dynamics of the lower esophageal sphincter (LES). A micro-oscillator actively emitting sound wave at 16 kHz is located at one side of the LES, and a miniature microphone is located at the other side of the sphincter to capture the sound generated from the oscillator. Thus, the dynamics of the opening and closing of the LES can be quantitatively assessed. In this paper, experiments are conducted utilizing an LES motility dynamics simulator. The sound strength is captured by the microphone and is correlated to the level of LES opening and closing controlled by the simulator. Measurements from the simulator model show statistically significant (p < 0.05) Pearson correlation coefficients (0.905 on the average in quiet environment and 0.736 on the average in noisy environment, D.O.F. = 9). Measuring the level of LES opening and closing has the potential to become a valuable diagnostic technique for understanding LES dysfunction and the disorders associated with it. PMID- 25120161 TI - A wireless portable high temperature data monitor for tunnel ovens. AB - Tunnel ovens are widely used in the food industry to produce biscuits and pastries. In order to obtain a high quality product, it is very important to control the heat transferred to each piece of dough during baking. This paper proposes an innovative, non-distorting, low cost wireless temperature measurement system, called "eBiscuit", which, due to its size, format and location in the metal rack conveyor belt in the oven, is able to measure the temperature a real biscuit experience while baking. The temperature conditions inside the oven are over 200 degrees C for several minutes, which could damage the "eBiscuit" electronics. This paper compares several thermal insulating materials that can be used in order to avoid exceeding the maximum operational conditions (80 degrees C) in the interior of the "eBiscuit. The data registered is then transmitted to a base station where information can be processed to obtain an oven model. The experimental results with real tunnel ovens confirm its good performance, which allows detecting production anomalies early on. PMID- 25120162 TI - Flexible capacitive electrodes for minimizing motion artifacts in ambulatory electrocardiograms. AB - This study proposes the use of flexible capacitive electrodes for reducing motion artifacts in a wearable electrocardiogram (ECG) device. The capacitive electrodes have conductive foam on their surface, a shield, an optimal input bias resistor, and guarding feedback. The electrodes are integrated in a chest belt, and the acquired signals are transmitted wirelessly for ambulatory heart rate monitoring. We experimentally validated the electrode performance with subjects standing and walking on a treadmill at speeds of up to 7 km/h. The results confirmed the highly accurate heart rate detection capacity of the developed system and its feasibility for daily-life ECG monitoring. PMID- 25120163 TI - A group neighborhood average clock synchronization protocol for wireless sensor networks. AB - Clock synchronization is a very important issue for the applications of wireless sensor networks. The sensors need to keep a strict clock so that users can know exactly what happens in the monitoring area at the same time. This paper proposes a novel internal distributed clock synchronization solution using group neighborhood average. Each sensor node collects the offset and skew rate of the neighbors. Group averaging of offset and skew rate value are calculated instead of conventional point-to-point averaging method. The sensor node then returns compensated value back to the neighbors. The propagation delay is considered and compensated. The analytical analysis of offset and skew compensation is presented. Simulation results validate the effectiveness of the protocol and reveal that the protocol allows sensor networks to quickly establish a consensus clock and maintain a small deviation from the consensus clock. PMID- 25120164 TI - Active in-database processing to support ambient assisted living systems. AB - As an alternative to the existing software architectures that underpin the development of smart homes and ambient assisted living (AAL) systems, this work presents a database-centric architecture that takes advantage of active databases and in-database processing. Current platforms supporting AAL systems use database management systems (DBMSs) exclusively for data storage. Active databases employ database triggers to detect and react to events taking place inside or outside of the database. DBMSs can be extended with stored procedures and functions that enable in-database processing. This means that the data processing is integrated and performed within the DBMS. The feasibility and flexibility of the proposed approach were demonstrated with the implementation of three distinct AAL services. The active database was used to detect bed-exits and to discover common room transitions and deviations during the night. In-database machine learning methods were used to model early night behaviors. Consequently, active in database processing avoids transferring sensitive data outside the database, and this improves performance, security and privacy. Furthermore, centralizing the computation into the DBMS facilitates code reuse, adaptation and maintenance. These are important system properties that take into account the evolving heterogeneity of users, their needs and the devices that are characteristic of smart homes and AAL systems. Therefore, DBMSs can provide capabilities to address requirements for scalability, security, privacy, dependability and personalization in applications of smart environments in healthcare. PMID- 25120165 TI - Dielectric and terahertz spectroscopy of polarizable and nonpolarizable water models: a comparative study. AB - Using extensive classical molecular dynamics simulations, we compute the dielectric and far-infrared spectra of nine popular water models, including polarizable and nonpolarizable ones. We analyze the dielectric spectra using a two-relaxation model that allows one to extract the characteristic time of both the main dielectric relaxation and the fast relaxation. The use of a Cole-Cole functional form permits also quantitative assessment of the absence of deviations from the Debye form of the main dielectric peak. In the THz region of the spectrum, we compute the infrared absorbance caused by molecular libration, which appears to be qualitatively different for three main groups of molecular models. The complexity of the librational band is further investigated by decomposing the spectrum into the contributions of water fractions with a different number of hydrogen-bonded neighbors. PMID- 25120166 TI - Subcellular localization of DAXX influence ox-LDL induced apoptosis in macrophages. AB - Here we aimed to evaluate the effects of DAXX subcellular localization on ox-LDL induced macrophages apoptosis. Cytoplasmic localization vector DAXX-W621A and nuclear localization vector DAXX-S667A were constructed by point mutation in DAXX. Blank vector, full length DAXX, DAXX-W621A, DAXX-S667A was transfect into RAW264.7 cells, respectively. Then the cells were incubated with 100 mg/ml ox-LDL for 48 h. Immunofluorescent assay was used to assay the localization of DAXX. MTT and Flow cytometry was used to determine cellular viability and apoptosis. RT-PCR and Western blot were used to analyze the expression levels. A significantly increased expression of DAXX was found in transfected cells of DAXX. The content of DAXX in nucleus was significantly increased in DAXX(S667A), and DAXX was significantly increased in cytoplasm of DAXX(W621A). Besides, we found DAXX was mainly expressed in nucleus with a low-level expression in cytoplasm through immunofluorescence. However in DAXX(W621A) group, the DAXX began to transferred to cytoplasm, which exhibited significant florescence. After treated with ox-LDL, the cytoactive of DAXX-W621A exhibited significantly decreased level when compared DAXX group. However, after added inhibitor LMB, the inhibition was relieved. The cell viability was also significantly increased in DAXX-S667A group. The results of apoptosis rates were similar in each group. Furthermore, we found the expression of ASK1 and JNK was also consistent with the apoptosis rates. Cytoplasmic localization of DAXX can increase injury sensitivity of ox-LDL on cells, and nuclear localization can antagonise the effect of ox-LDL. Besides, it is certified ox-LDL induced apoptosis is mainly through ASK1-JNK pathway. PMID- 25120167 TI - The association between KL polymorphism and prostate cancer risk in Korean patients. AB - The Klotho (KL) gene is a classical "aging suppressor" gene. Although recent studies have shown that KL participates in the progression of several types of human cancers, the relationship between KL polymorphism and prostate cancer was unknown. The present study aimed to investigate the association between KL genetic polymorphisms and prostate cancer. Twenty-five common single nucleotide polymorphisms (SNPs) in KL gene (including KL gene polymorphism C1818T in exon 4) were assessed in 272 prostate cancer cases and 173 controls. Single-locus analyses were conducted using unconditional logistic regression. In addition, we did a haplotype analysis for the 25 KL SNPs tested. CC genotype of C1548T KL polymorphism had approximately twofold increased prostate cancer risk compared with the homozygous genotype TT and heterozygote CT (odds ratio 1.85 [95% CI, 1.09-3.12], P = 0.02). We also found that non-T allele carriers had significantly higher prostate cancer risk associated with the prostate cancer clinical characteristics (tumor stage or Gleason score). Our findings suggested that the C1548T polymorphism of KL gene is associated with the prostate cancer and may act as a risk factor for the development of prostate cancer. PMID- 25120168 TI - Biochemical and molecular characterization of Avena indolines and their role in kernel texture. AB - Among cereals, Avena sativa is characterized by an extremely soft endosperm texture, which leads to some negative agronomic and technological traits. On the basis of the well-known softening effect of puroindolines in wheat kernel texture, in this study, indolines and their encoding genes are investigated in Avena species at different ploidy levels. Three novel 14 kDa proteins, showing a central hydrophobic domain with four tryptophan residues and here named vromindoline (VIN)-1,2 and 3, were identified. Each VIN protein in diploid oat species was found to be synthesized by a single Vin gene whereas, in hexaploid A. sativa, three Vin-1, three Vin-2 and two Vin-3 genes coding for VIN-1, VIN-2 and VIN-3, respectively, were described and assigned to the A, C or D genomes based on similarity to their counterparts in diploid species. Expression of oat vromindoline transgenes in the extra-hard durum wheat led to accumulation of vromindolines in the endosperm and caused an approximate 50 % reduction of grain hardness, suggesting a central role for vromindolines in causing the extra-soft texture of oat grain. Further, hexaploid oats showed three orthologous genes coding for avenoindolines A and B, with five or three tryptophan residues, respectively, but very low amounts of avenoindolines were found in mature kernels. The present results identify a novel protein family affecting cereal kernel texture and would further elucidate the phylogenetic evolution of Avena genus. PMID- 25120169 TI - Genome-wide identification of citrus ATP-citrate lyase genes and their transcript analysis in fruits reveals their possible role in citrate utilization. AB - ATP-citrate lyase (ACL, EC4.1.3.8) catalyzes citrate to oxaloacetate and acetyl CoA in the cell cytosol, and has important roles in normal plant growth and in the biosynthesis of some secondary metabolites. We identified three ACL genes, CitACLalpha1, CitACLalpha2, and CitACLbeta1, in the citrus genome database. Both CitACLalpha1 and CitACLalpha2 encode putative ACL alpha subunits with 82.5 % amino acid identity, whereas CitACLbeta1 encodes a putative ACL beta subunit. Gene structure analysis showed that CitACLalpha1 and CitACLalpha2 had 12 exons and 11 introns, and CitACLbeta1 had 16 exons and 15 introns. CitACLalpha1 and CitACLbeta1 were predominantly expressed in flower, and CitACLalpha2 was predominantly expressed in stem and fibrous roots. As fruits ripen, the transcript levels of CitACLalpha1, CitACLbeta1, and/or CitACLalpha2 in cultivars 'Niuher' and 'Owari' increased, accompanied by significant decreases in citrate content, while their transcript levels decreased significantly in 'Egan No. 1' and 'Iyokan', although citrate content also decreased. In 'HB pummelo', in which acid content increased as fruit ripened, and in acid-free pummelo, transcript levels of CitACLalpha2, CitACLbeta1, and/or CitACLalpha1 increased. Moreover, mild drought stress and ABA treatment significantly increased citrate contents in fruits. Transcript levels of the three genes were significantly reduced by mild drought stress, and the transcript level of only CitACLbeta1 was significantly reduced by ABA treatment. Taken together, these data indicate that the effects of ACL on citrate use during fruit ripening depends on the cultivar, and the reduction in ACL gene expression may be attributed to citrate increases under mild drought stress or ABA treatment. PMID- 25120171 TI - The clock is ticking: the sound of a ticking clock speeds up women's attitudes on reproductive timing. AB - The "biological clock" serves as a powerful metaphor that reflects the constraints posed by female reproductive biology. The biological clock refers to the progression of time from puberty to menopause, marking the period during which women can conceive children. Findings from two experiments suggest that priming the passage of time through the sound of a ticking clock influenced various aspects of women's (but not men's) reproductive timing. Moreover, consistent with recent research from the domain of life history theory, those effects depended on women's childhood socioeconomic status (SES). The subtle sound of a ticking clock led low (but not high) SES women to reduce the age at which they sought to get married and have their first child (Study 1), as well as the priority they placed on the social status and long-term earning potential of potential romantic partners (Study 2). Findings suggest that early developmental sensitization processes can interact with subtle environmental stimuli to affect reproductive timing during adulthood. PMID- 25120170 TI - Faculty survey to assess research literacy and evidence-informed practice interest and support at Pacific College of Oriental Medicine. AB - CONTEXT: Educating healthcare practitioners to understand, critically evaluate, and apply evidence to the clinical practice of complementary and alternative medicine has been an important initiative for the National Institutes of Health National Center for Complementary and Alternative Medicine. OBJECTIVE: To determine the self-assessed research skills and interest of faculty at Pacific College of Oriental Medicine (New York campus) and their likely support of, and participatory interest in, an evidence-based medicine (EBM) training program. DESIGN: The survey was administered in Survey Monkey. All questions were close ended with 5-point Likert answers, except for one open-ended question at the end of the survey. SETTING: One of three campuses of Pacific College of Oriental Medicine (PCOM), the largest Chinese medicine college in the United States. PARTICIPANTS: 102 faculty employed at PCOM. RESULTS: The response rate was 88.7%. Responses illustrated a generally high degree of interest and support for research, EBM, and institutional participation in research activities. Faculty who responded to the open-ended question (19.6% of respondents) expressed concerns about the relevance of research to Chinese medicine and the possibility of co-option by biomedicine. CONCLUSIONS: While faculty were overall supportive and interested in research and EBM, the results are consistent with the hypothesis that success of EBM training programs could be enhanced by soliciting and addressing faculty concerns and by being inclusive of approaches that honor the traditions of Chinese medicine and its own forms of clinical evidence. PMID- 25120173 TI - Size, dimensionality, and strong electron correlation in nanoscience. AB - In electronic structure theory, electron-electron repulsion is normally considered only in an average (or mean field) sense, for example, in a single Hartree-Fock determinant. This is the simple molecular orbital model, which is often a good approximation for molecules. In infinite systems, this averaging treatment leads to delocalized electronic bands, an excellent description of bulk 3D sp(3) semiconductors. However, in reality electrons try to instantaneously avoid each other; their relative motion is correlated. Strong electron-electron repulsion and correlation create new collective states and cause new femtosecond kinetic processes. This is especially true in 1D and 2D systems. The quantum size effect, a single electron property, is widely known: the band gap increases with decreasing size. This Account focuses on the experimental consequences of strong correlation. We first describe pi-pi* excited states in carbon nanotubes (CNTs). To obtain the spectra of individual CNTs, we developed a white-light, right-angle resonant Rayleigh scattering method. Discrete exciton transitions dominate the optical absorption spectra of both semiconducting and metallic tubes. Excitons are bound neutral excited states in which the electron and hole tightly orbit each other due to their mutual Coulomb attraction. We then describe more generally the independent roles of size and dimensionality in nanoelectronic structure, using additional examples from graphene, trans-polyacetylene chains, transition metal dichalcogenides, organic/inorganic Pb iodide perovskites, quantum dots, and pentacene van der Waals crystals. In 1D and 2D chemical systems, the electronic band structure diagram can be a poor predictor of properties if explicit correlation is not considered. One- and two-dimensional systems show quantum confinement and especially strong correlation as compared with their 3D parent systems. The Coulomb interaction is enhanced because the electrons are on the surface. One- and two-dimensional systems can exhibit essentially molecular properties even though they are infinite in size. Zero dimensional Qdots show quantum confinement and modest electron correlation. Correlation is weak in 3D bulk semiconductors. Strongly correlated electronic states can behave as if they have fractional charge and effectively separate the spin and charge of the electron. This is apparent in the "soliton" state of polyacetylene, the fractional charge quantum Hall state of graphene, and the Luttinger electrical conductivity of metallic CNTs. PMID- 25120172 TI - Short sleep duration reduces the risk of nonalcoholic fatty liver disease onset in men: a community-based longitudinal cohort study. AB - BACKGROUND: Epidemiologic studies show an association between short sleep duration and the presence of nonalcoholic fatty liver disease (NAFLD). This study examined the association between short sleep duration and the onset of NAFLD. METHODS: This community-based, retrospective, longitudinal cohort study included 6,370 Japanese subjects who had undergone annual health check-ups more than twice at a single center between April 2003 and March 2010. After excluding 3,941 subjects, the records of 2,429 Japanese subjects were reviewed. RESULTS: Two groups comprised the study cohort: those with short (<= 6 h) sleep durations (n = 1,543) and those with moderate (7-8 h) sleep durations (n = 886). During the observation period, 296 subjects developed NAFLD. Multivariate analysis identified an association between short sleep duration and the reduced onset of NAFLD in men (odds ratio: 0.551, 95% confidence interval 0.365-0.832, p = 0.005). There was no association between short sleep duration and NAFLD onset in women. The prevalence of NAFLD onset in men increased significantly as sleep duration increased, as follows: 12.5, 18.4, and 27.4% among subjects who had sleep durations of <= 4, 5-6, and 7-8 h, respectively (p = 0.02). CONCLUSIONS: This study demonstrates an association between sleep duration and NAFLD onset. Short sleep duration reduced the risk of NAFLD onset in men. Correct recognition is important to prevent disease progression and further complications. PMID- 25120174 TI - Incremental predictive value of natriuretic peptides for prognosis in the chronic stable heart failure population: a systematic review. AB - The aim of this study was to determine whether measurement of natriuretic peptides independently adds incremental predictive value for mortality and morbidity in patients with chronic stable heart failure (CSHF). We electronically searched Medline(r), EmbaseTM, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL from 1989 to June 2012. We also searched reference lists of included articles, systematic reviews, and the gray literature. Studies were screened for eligibility criteria and assessed for methodological quality. Data were extracted on study design, population demographics, assay cutpoints, prognostic risk prediction model covariates, statistical methods, outcomes, and results. One hundred and eighty three studies were identified as prognostic in the systematic review. From these, 15 studies (all NT-proBNP) considered incremental predictive value in CSHF subjects. Follow-up varied from 12 to 37 months. All studies presented at least one estimate of incremental predictive value of NT-proBNP relative to the base prognostic model. Using discrimination or likelihood statistics, these studies consistently showed that NT-proBNP increased model performance. Three studies used re-classification and model validation computations to establish incremental predictive value; these studies showed less consistency with respect to added value. Although there were differences in the base risk prediction models, assay cutpoints, and lengths of follow-up, there was consistency in NT-proBNP adding incremental predictive value for prognostic models in chronic stable CSHF patients. The limitations in the literature suggest that studies designed to evaluate prognostic models should be undertaken to evaluate the incremental value of natriuretic peptide as a predictor of mortality and morbidity in CSHF. PMID- 25120175 TI - Quantitative short-wave infrared multispectral imaging of in vivo tissue optical properties. AB - Extending the wavelength range of spatial frequency domain imaging (SFDI) into the short-wave infrared (SWIR) has the potential to provide enhanced sensitivity to chromophores such as water and lipids that have prominent absorption features in the SWIR region. Here, we present, for the first time, a method combining SFDI with unstructured (zero spatial frequency) illumination to extract tissue absorption and scattering properties over a wavelength range (850 to 1800 nm) largely unexplored by previous tissue optics techniques. To obtain images over this wavelength range, we employ a SWIR camera in conjunction with an SFDI system. We use SFDI to obtain in vivo tissue reduced scattering coefficients at the wavelengths from 850 to 1050 nm, and then use unstructured wide-field illumination and an extrapolated power-law fit to this scattering spectrum to extract the absorption spectrum from 850 to 1800 nm. Our proof-of-principle experiment in a rat burn model illustrates that the combination of multispectral SWIR imaging, SFDI, and unstructured illumination can characterize in vivo changes in skin optical properties over a greatly expanded wavelength range. In the rat burn experiment, these changes (relative to normal, unburned skin) included increased absorption and increased scattering amplitude and slope, consistent with changes that we previously reported in the near-infrared using SFDI. PMID- 25120176 TI - Conservative management of vestibular schwannomas of 15 to 31 mm intracranial diameter. AB - OBJECTIVE: To study the natural course of vestibular schwannomas 15 to 31 mm in diameter. METHODS: A retrospective study of 45 patients conservatively managed with interval scanning was performed. Outcome measures were: changes in tumour size, clinical features and hearing. A tumour was considered to be growing if it increased in size by more than 2 mm. RESULTS: Initial tumour sizes ranged from 15 to 31 mm, with a mean (+/- standard deviation) diameter of 20.1 +/- 4.3 mm. The duration of follow up ranged from 6 months to 14 years (median, 3 years). Tumours grew in 11 cases (24.4 per cent), remained stable in 30 cases (66.7 per cent) and regressed in 4 cases (8.9 per cent). The overall mean tumour growth rate was 0.9 +/- 2.2 mm per year; in growing tumours, it was 3.6 +/- 2.9 mm per year. CONCLUSION: Outcomes were similar to those reported for smaller tumours. These findings suggest that patients with medium or moderately large tumours can be safely offered an initial period of conservative management before intervention is considered. PMID- 25120177 TI - Personalizing energy expenditure estimation using physiological signals normalization during activities of daily living. AB - In this paper we propose a generic approach to reduce inter-individual variability of different physiological signals (HR, GSR and respiration) by automatically estimating normalization parameters (e.g. baseline and range). The proposed normalization procedure does not require a dedicated personal calibration during system setup. On the other hand, normalization parameters are estimated at system runtime from sedentary and low intensity activities of daily living (ADLs), such as lying and walking. When combined with activity-specific energy expenditure (EE) models, our normalization procedure improved EE estimation by 15 to 33% in a study group of 18 participants, compared to state of the art activity-specific EE models combining accelerometer and non-normalized physiological signals. PMID- 25120178 TI - Magnitude of perceived depth of multiple stereo transparent surfaces. AB - According to the geometric relational expression of binocular stereopsis, for a given viewing distance the magnitude of the perceived depth of objects would be the same, as long as the disparity magnitudes were the same. However, we found that this is not necessarily the case for random-dot stereograms that depict parallel, overlapping, transparent stereoscopic surfaces (POTS). The data from five experiments indicated that (1) the magnitude of perceived depth between the two outer surfaces of a three- or a four-POTS configuration can be smaller than that for an identical pair of stereo surfaces of a two-POTS configuration for the range of disparities that we used (5.2-19.4 arcmin); (2) this phenomenon can be observed irrespective of the total dot density of a POTS configuration, at least for the range that we used (1.1-3.3 dots/deg(2)); and (3) the magnitude of perceived depth between the two outer surfaces of a POTS configuration can be reduced as the total number of stereo surfaces is increased, up to four surfaces. We explained these results in terms of a higher-order process or processes, with an output representing perceived depth magnitude, which is weakened when the number of its surfaces is increased. PMID- 25120179 TI - The projected hand illusion: component structure in a community sample and association with demographics, cognition, and psychotic-like experiences. AB - The projected hand illusion (PHI) is a variant of the rubber hand illusion (RHI), and both are commonly used to study mechanisms of self-perception. A questionnaire was developed by Longo et al. (2008) to measure qualitative changes in the RHI. Such psychometric analyses have not yet been conducted on the questionnaire for the PHI. The present study is an attempt to validate minor modifications of the questionnaire of Longo et al. to assess the PHI in a community sample (n = 48) and to determine the association with selected demographic (age, sex, years of education), cognitive (Digit Span), and clinical (psychotic-like experiences) variables. Principal components analysis on the questionnaire data extracted four components: Embodiment of "Other" Hand, Disembodiment of Own Hand, Deafference, and Agency-in both synchronous and asynchronous PHI conditions. Questions assessing "Embodiment" and "Agency" loaded onto orthogonal components. Greater illusion ratings were positively associated with being female, being younger, and having higher scores on psychotic-like experiences. There was no association with cognitive performance. Overall, this study confirmed that self-perception as measured with PHI is a multicomponent construct, similar in many respects to the RHI. The main difference lies in the separation of Embodiment and Agency into separate constructs, and this likely reflects the fact that the "live" image of the PHI presents a more realistic picture of the hand and of the stroking movements of the experimenter compared with the RHI. PMID- 25120180 TI - Large-scale analysis of posttranslational modifications in the hippocampus of patients with Alzheimer's disease using pI shift and label-free quantification without enrichment. AB - Posttranslational modifications modulate protein function in cells. Global analysis of multiple posttranslational modifications can provide insight into physiology and disease, but presents formidable challenges. In the present study, we used a technique that does not require target enrichment to analyze alterations in the phosphorylation and ubiquitination of proteins from patients with Alzheimer's disease (AD). Guided by our previous findings, we applied three strategies to further our understanding of the dysregulation of posttranslationally modified proteins. We first identified phosphorylation sites by determining peptide pI shifts using OFFGEL. Second, using tandem mass spectrometry, we determined the ubiquitination status of the proteins using an assay for a trypsin digestion remnant of ubiquitination (Gly-Gly). Third, for large-scale discovery, we quantified the global differences in protein expression. Of the proteins expressed in AD tissue at levels of 2.0 or greater compared with controls, 60 were phosphorylated and 56 were ubiquitinated. Of the proteins expressed at levels of 0.5 or lower compared with controls, 81 were phosphorylated and 56 were ubiquitinated. Approximately 98 % of the phosphopeptides exhibited a pI shift. We identified 112 new phosphorylation sites (51.38 %), and 92 new ubiquitination sites (96.84 %). Taken together, our findings suggest that analysis of the alterations in posttranslationally modified proteins may contribute to understanding the pathogenesis of AD and other diseases. PMID- 25120181 TI - Characterization and analysis of structural isomers of dimethyl methoxypyrazines in cork stoppers and ladybugs (Harmonia axyridis and Coccinella septempunctata). AB - The three constitutional isomers of dimethyl-substituted methoxypyrazines: 3,5 dimethyl-2-methoxypyrazine 1; 2,5-dimethyl-3-methoxypyrazine 2; and 2,3-dimethyl 5-methoxypyrazine 3 are potent flavor compounds with similar mass spectrometric, gas chromatographic, and nuclear magnetic resonance spectroscopic behavior. Therefore, unambiguous analytical determination is critical, particularly in complex matrices. The unequivocal identification of 1-3 could be achieved by homo and heteronuclear NMR correlation experiments. The observed mass fragmentation for 1-3 is proposed and discussed, benefitting from synthesized partially deuterated 1 and 2. On common polar and apolar stationary phases used in gas chromatography (GC) 1 and 2 show similar behavior whereas 3 can be separated. In our focus on off-flavor analysis with respect to wine aroma, 1 has been described as a "moldy" off-flavor compound in cork and 2 as a constituent in Harmonia axyridis contributing to the so-called "ladybug taint," whereas 3 has not yet been described as a constituent of wine aroma. A successful separation of 1 and 2 could be achieved on octakis-(2,3-di-O-pentyl-6-O-methyl)-gamma-cyclodextrin as stationary phase in GC. Applying heart-cut multidimensional GC analysis with tandem mass spectrometric detection we could confirm the presence of 1 as a "moldy" off-flavor compound in cork. However, in the case of Harmonia axyridis, a previous identification of 2 has to be reconsidered. In our experiments we identified the constitutional isomer 1, which was also found in Coccinella septempunctata, another species discussed with respect to the "ladybug taint." The analysis of such structurally related compounds is a demonstrative example for the importance of a chromatographic separation, as mass spectrometric data by itself could not guarantee the unequivocal identification. PMID- 25120182 TI - A wide range optical pH sensor for living cells using Au@Ag nanoparticles functionalized carbon nanotubes based on SERS signals. AB - p-Aminothiophenol (pATP) functionalized multi-walled carbon nanotubes (MWCNTs) have been demonstrated as an efficient pH sensor for living cells. The proposed sensor employs gold/silver core-shell nanoparticles (Au@Ag NPs) functionalized MWCNTs hybrid structure as the surface-enhanced Raman scattering (SERS) substrate and pATP molecules as the SERS reporters, which possess a pH-dependent SERS performance. By using MWCNTs as the substrate to be in a state of aggregation, the pH sensing range could be extended to pH 3.0~14.0, which is much wider than that using unaggregated Au@Ag NPs without MWCNTs. Furthermore, the pH-sensitive performance was well retained in living cells with a low cytotoxicity. The developed SERS-active MWCNTs-based nanocomposite is expected to be an efficient intracellular pH sensor for bio-applications. PMID- 25120183 TI - Relating surface-enhanced Raman scattering signals of cells to gold nanoparticle aggregation as determined by LA-ICP-MS micromapping. AB - The cellular response to nanoparticle exposure is essential in various contexts, especially in nanotoxicity and nanomedicine. Here, 14-nm gold nanoparticles in 3T3 fibroblast cells are investigated in a series of pulse-chase experiments with a 30-min incubation pulse and chase times ranging from 15 min to 48 h. The gold nanoparticles and their aggregates are quantified inside the cellular ultrastructure by laser ablation inductively coupled plasma mass spectrometry micromapping and evaluated regarding the surface-enhanced Raman scattering (SERS) signals. In this way, both information about their localization at the micrometre scale and their molecular nanoenvironment, respectively, is obtained and can be related. Thus, the nanoparticle pathway from endocytotic uptake, intracellular processing, to cell division can be followed. It is shown that the ability of the intracellular nanoparticles and their accumulations and aggregates to support high SERS signals is neither directly related to nanoparticle amount nor to high local nanoparticle densities. The SERS data indicate that aggregate geometry and interparticle distances in the cell must change in the course of endosomal maturation and play a critical role for a specific gold nanoparticle type in order to act as efficient SERS nanoprobe. This finding is supported by TEM images, showing only a minor portion of aggregates that present small interparticle spacing. The SERS spectra obtained after different chase times show a changing composition and/or structure of the biomolecule corona of the gold nanoparticles as a consequence of endosomal processing. PMID- 25120185 TI - Biotransformation and detectability of the designer drug 2,5-dimethoxy-4 propylphenethylamine (2C-P) studied in urine by GC-MS, LC-MS(n), and LC-high resolution-MS(n). AB - 2,5-Dimethoxy-4-propylphenethylamine (2C-P) is a hallucinogenic designer drug of the phenethylamine class, the so-called 2Cs, named according to the ethyl spacer between the nitrogen and the aromatic ring. The aims of the present work were to identify the phases I and II metabolites of 2C-P. In addition, the detectability of 2C-P and its metabolites in urine as proof of an intake in clinical or forensic cases was tested. According to the identified metabolites, the following pathways were proposed: N-acetylation; deamination followed by reduction to the corresponding alcohol and oxidation to carbonic acid; mono- and bis-hydroxylation at different positions; mono- and bis-O-demethylation, followed by glucuronidation, sulfation, or both; and combination of these steps. Proof of an intake of a common user's dose of 2C-P was possible by both standard urine screening approaches, the GC-MS as well as the LC-MS(n) approach. PMID- 25120184 TI - Emerging trends in precision fabrication of microapertures to support suspended lipid membranes for sensors, sequencing, and beyond. AB - Suspended lipid membranes, also called black lipid membranes (BLMs), are an important model system that approximates the lipid bilayer environment of cell membranes. Increasingly, BLMs are utilized in sensing strategies that harness high sensitivity measurements of ion flux across the membrane, typically facilitated by ion channel proteins. BLMs are suspended across microapertures that connect two otherwise isolated fluidic compartments, and the precision fabrication of such microapertures can contribute to the stability and performance of the resulting BLM. Here, we highlight two emerging trends in the precision fabrication of microapertures for BLM formation: microfabrication in silicon-based thin film substrates, and microfabrication in the negative photoresist material SU-8. Four unique fabrication strategies are outlined, and we project the impact that these microfabrication strategies will have for BLM integrated bioanalytical technologies. PMID- 25120186 TI - Reproducibility of retention time and peak area in comprehensive two-dimensional liquid chromatography. AB - Comprehensive two-dimensional liquid chromatography is used to separate anionic, nonionic, and amphoteric surfactants by substance class, alkyl chain distribution, and degree of ethoxylation. A nearly orthogonal system with a hydrophilic interaction chromatography (HILIC) phase in the first and a reversed phase material in the second dimension is applied to generate a separation with maximum peak capacity. The potential of the developed method is demonstrated by the reproducibility of retention time and peak area, which shows standard deviations less than 5 % and the analysis of real samples. An external calibration and the standard addition method were applied to determine unknown concentrations for the alkyl chain homologues of a betaine and for one ethoxylate (EO) homologue of a fatty alcohol ethoxylate in a sample mixture. PMID- 25120187 TI - Investigating the contribution of the active site environment to the slow reaction of hypoxia-inducible factor prolyl hydroxylase domain 2 with oxygen. AB - The prolyl hydroxylase domain proteins (PHDs) catalyse the post-translational hydroxylation of the hypoxia-inducible factor (HIF), a modification that regulates the hypoxic response in humans. The PHDs are Fe(II)/2-oxoglutarate (2OG) oxygenases; their catalysis is proposed to provide a link between cellular HIF levels and changes in O2 availability. Transient kinetic studies have shown that purified PHD2 reacts slowly with O2 compared with some other studied 2OG oxygenases, a property which may be related to its hypoxia-sensing role. PHD2 forms a stable complex with Fe(II) and 2OG; crystallographic and kinetic analyses indicate that an Fe(II)-co-ordinated water molecule, which must be displaced before O2 binding, is relatively stable in the active site of PHD2. We used active site substitutions to investigate whether these properties are related to the slow reaction of PHD2 with O2. While disruption of 2OG binding in a R383K variant did not accelerate O2 activation, we found that substitution of the Fe(II)-binding aspartate for a glutamate residue (D315E) manifested significantly reduced Fe(II) binding, yet maintained catalytic activity with a 5-fold faster reaction with O2. The results inform on how the precise active site environment of oxygenases can affect rates of O2 activation and provide insights into limiting steps in PHD catalysis. PMID- 25120188 TI - Copeptin is not a useful biomarker for small-for-gestational-age: a case control study. AB - OBJECTIVE: To investigate copeptin as a biomarker for small-for-gestational-age. METHODS: We conducted a nested case-control study on maternal copeptin levels measured in gestational week 12 and 19 and risk of small-for-gestational age. Cases were defined as pregnant women who delivered a small-for-gestational-age infant. Small-for-gestational age was defined as a birth weight - 22% or less than expected according to gestational age (n = 39). Controls were pregnant women who delivered a normal-weight infant (n = 119). The copeptin ultrasensitive Kryptor kit (BRAHMS) was used to determine copeptin in maternal serum. We established reference ranges for copeptin by 95% prediction intervals with 90% confidence intervals. Paired and unpaired t-tests were performed to test the null hypothesis of no difference in copeptin levels within and between the groups. RESULTS: The reference intervals for copeptin in normal pregnancies were 1.24 5.51 pmol/L (90% confidence intervals on upper and lower limit were 1.13-1.37 and 5.00-6.08 pmol/L) at gestational week 12, and 1.30-5.09 pmol/L (90% confidence intervals were 1.19-1.42 and 4.65-5.57 pmol/L) at gestational week 19. Copeptin levels decreased from week 12-19 in cases (p = 0.02), whereas no change was observed in controls (p = 0.61). We found no difference in copeptin levels in cases compared to controls in gestational week 12 (p = 0.10) and week 19 (p = 0.81). CONCLUSION: The present study could not demonstrate copeptin as a novel biomarker for small-for-gestational-age. PMID- 25120189 TI - Gate-opening gas adsorption and host-guest interacting gas trapping behavior of porous coordination polymers under applied AC electric fields. AB - The gate-opening adsorption behavior of the one-dimensional chain compound [Ru2(4 Cl-2-OMePhCO2)4(phz)] (1; 4-Cl-2-OMePhCO2(-) = 4-chloro-o-anisate; phz = phenazine) for various gases (O2, NO, and CO2) was electronically monitored in situ by applying ac electric fields to pelletized samples attached to a cryostat, which was used to accurately control the temperature and gas pressure. The gate opening and -closing transitions induced by gas adsorption/desorption, respectively, were accurately monitored by a sudden change in the real part of permittivity (epsilon'). The transition temperature (TGO) was also found to be dependent on the applied temperature and gas pressure according to the Clausius Clapeyron equation. This behavior was also observed in the isostructural compound [Rh2(4-Cl-2-OMePhCO2)4(phz)] (2), which exhibited similar gate-opening adsorption properties, but was not detected in the nonporous gate-inactive compound [Ru2(o OMePhCO2)4(phz)] (3). Furthermore, the imaginary part of permittivity (epsilon") effectively captured the electronic perturbations of the samples induced by the introduced guest molecules. Only the introduction of NO resulted in the increase of the sample's electronic conductivity for 1 and 3, but not for 2. This behavior indicates that electronic host-guest interactions were present, albeit very weak, at the surface of sample 1 and 3, i.e., through grain boundaries of the sample, which resulted in perturbation of the conduction band of this material's framework. This technique involving the in situ application of ac electric fields is useful not only for rapidly monitoring gas sorption responses accompanied by gate-opening/-closing structural transitions but also potentially for the development of molecular framework materials as chemically driven electronic devices. PMID- 25120190 TI - Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor initiating cells. AB - Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found to be critically important for the maintenance of tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the tumor from which they are identified, and are drivers of recurrence in numerous cancers. In this study, telomerase enzymatic activity was directly measured and inhibited to assess the therapeutic potential of targeting telomerase. Telomerase repeat amplification protocol (TRAP) (n = 36) and C-circle assay/telomere FISH/ATRX staining (n = 76) were performed on primary ependymomas to determine the prevalence and prognostic potential of telomerase activity or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms, respectively. Imetelstat, a phase 2 telomerase inhibitor, was used to elucidate the effect of telomerase inhibition on proliferation and tumorigenicity in established cell lines (BXD-1425EPN, R254), a primary TIC line (E520) and xenograft models of pediatric ependymoma. Over 60 % of pediatric ependymomas were found to rely on telomerase activity to maintain telomeres, while no ependymomas showed evidence of ALT. Children with telomerase-active tumors had reduced 5-year progression free survival (29 +/- 11 vs 64 +/- 18 %; p = 0.03) and overall survival (58 +/- 12 vs 83 +/- 15 %; p = 0.05) rates compared to those with tumors lacking telomerase activity. Imetelstat inhibited proliferation and self-renewal by shortening telomeres and inducing senescence in vitro. In vivo, Imetelstat significantly reduced subcutaneous xenograft growth by 40 % (p = 0.03) and completely abolished the tumorigenicity of pediatric ependymoma TICs in an orthotopic xenograft model. Telomerase inhibition represents a promising therapeutic approach for telomerase-active pediatric ependymomas found to characterize high-risk ependymomas. PMID- 25120192 TI - Anti-Abeta antibody target engagement: commentary regarding Watt et al. Acta Neuropathol 127:803-810 (2014). PMID- 25120191 TI - C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration. AB - Hexanucleotide repeat expansion in C9orf72 is the most common pathogenic mutation in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the lack of an ATG start codon, the repeat expansion is translated in all reading frames into dipeptide repeat (DPR) proteins, which form insoluble, ubiquitinated, p62-positive aggregates that are most abundant in the cerebral cortex and cerebellum. To specifically analyze DPR toxicity and aggregation, we expressed DPR proteins from synthetic genes containing a start codon but lacking extensive GGGGCC repeats. Poly-Gly-Ala (GA) formed p62-positive cytoplasmic aggregates, inhibited dendritic arborization and induced apoptosis in primary neurons. Quantitative mass spectrometry analysis to identify poly-GA co aggregating proteins revealed a significant enrichment of proteins of the ubiquitin-proteasome system. Among the other interacting proteins, we identified the transport factor Unc119, which has been previously linked to neuromuscular and axonal function, as a poly-GA co-aggregating protein. Strikingly, the levels of soluble Unc119 are strongly reduced upon poly-GA expression in neurons, suggesting a loss of function mechanism. Similar to poly-GA expression, Unc119 knockdown inhibits dendritic branching and causes neurotoxicity. Unc119 overexpression partially rescues poly-GA toxicity suggesting that poly-GA expression causes Unc119 loss of function. In C9orf72 patients, Unc119 is detectable in 9.5 % of GA inclusions in the frontal cortex, but only in 1.6 % of GA inclusions in the cerebellum, an area largely spared of neurodegeneration. A fraction of neurons with Unc119 inclusions shows loss of cytosolic staining. Poly GA-induced Unc119 loss of function may thereby contribute to selective vulnerability of neurons with DPR protein inclusions in the pathogenesis of C9orf72 FTLD/ALS. PMID- 25120194 TI - Effective implementation of health information technologies in U.S. hospitals. AB - OBJECTIVES: Two issues pertaining to the effective implementation of health information technologies (HITs) in U.S. hospitals are examined. First, which information technology (IT) system is better--a homegrown or an outsourced one? In the second issue, the critical role of in-house IT expertise/capabilities in the effective implementation of HITs is investigated. STUDY DESIGN/DATA COLLECTION: The data on type of HIT system and IT expertise/capabilities were collected from a national sample of senior executives of U.S. hospitals. The data on quality of patient care were gathered from the Hospital Compare Web site. FINDINGS: The quality of patient care was significantly higher in hospitals deploying a homegrown HIT system than hospitals deploying an outsourced HIT system. Furthermore, the professional competence and compelling vision of the chief information officer was found to be a major driver of another key IT capability of hospitals-professionalism of IT staff. The positive relationship of professionalism of IT staff with quality of patient care was mediated by proactive employee behavior. CONCLUSION: A homegrown HIT system achieves better quality of patient care than an outsourced one. The chief information officer's IT vision and the professional expertise and professionalism of IT staff are important IT capabilities in U.S. hospitals. PMID- 25120193 TI - Anti-Abeta antibody target engagement: a response to Siemers et al. PMID- 25120195 TI - Cumulative impact of periodic top-down communications on infection prevention practices and outcomes in two units. AB - BACKGROUND: The problem of interest in this study is the challenge of consistent implementation of evidence-based infection prevention practices at the unit level, a challenge broadly characterized as "change implementation failure." The theoretical literature suggests that periodic top-down communications promoting tacit knowledge exchanges across professional subgroups may be effective for enabling change in health care organizations. However, gaps remain in understanding the mechanisms by which top-down communications enable practice change at the unit level. Our study sought to both validate the theoretical literature and address this gap. PURPOSE: Correspondingly, this study posed two research questions. (1) What is the impact of periodic "top-down" communications on practice change at the unit level? (2) What are the "unit-level" communication dynamics enabling practice changes? Whereas this article focuses on addressing the first question, the second question has been addressed in an earlier Health Care Management Review article (Rangachari et al., 2013). METHODS: A prospective study was conducted in two intensive care units at an academic health center. Both units had low baseline adherence to central line bundle (CLB) and higher than-expected catheter-related bloodstream infections (CRBSIs). Periodic top-down communication interventions were conducted over 52 weeks to promote CLB adherence in both units. Simultaneously, the study examined (a) unit-level communication dynamics related to CLB through weekly "communication logs," completed by unit physicians, nurses, and managers, and (b) unit outcomes, that is, CLB adherence and CRBSI rates. FINDINGS: Both units showed increased adherence to CLB and significant, sustained declines in CRBSIs. Results showed that the interventions cumulatively had a significant negative (desired) impact on "catheter days," that is, central catheter use. PRACTICE IMPLICATIONS: Results help validate the theoretical literature and identify evidence-based management strategies for practice change at the unit level. They suggest that periodic top-down communications have the potential to modify interprofessional knowledge exchanges and enable practice change at the unit level, leading to significantly improved outcomes and reduced costs. PMID- 25120196 TI - Within-subject comparison of word recognition and spiral ganglion cell count in bilateral cochlear implant recipients. AB - OBJECTIVES: Although published reports have not demonstrated a positive correlation between the number of residual spiral ganglion cells (SGCs) and word recognition scores in patients with unilateral multichannel cochlear implants, this study was designed to retest this hypothesis in patients with bilateral multichannel cochlear implants. MATERIALS AND METHODS: From a pool of 133 temporal bones, all subjects with bilateral multichannel cochlear implants who were deafened bilaterally by the same etiology were studied. A total of 12 temporal bones from 6 subjects were identified and processed after death for histology. The SGCs were counted using standard techniques. The differences between left and right SGC counts as well as the differences in word recognition scores were calculated for each subject. Correlation analysis was performed between the differences of SGC counts and the differences of word recognition scores. RESULTS: Differences in SGC counts were highly correlated with the differences in word recognition scores (R = 0.934, p = 0.006). CONCLUSION: This study suggests higher residual SGCs predicted better performance after implantation in a given patient. The results also support attempts to identify factors which may promote survival of SGCs. PMID- 25120197 TI - Documentation and localization of force-mediated filamin A domain perturbations in moving cells. AB - Endogenously and externally generated mechanical forces influence diverse cellular activities, a phenomenon defined as mechanotransduction. Deformation of protein domains by application of stress, previously documented to alter macromolecular interactions in vitro, could mediate these effects. We engineered a photon-emitting system responsive to unfolding of two repeat domains of the actin filament (F-actin) crosslinker protein filamin A (FLNA) that binds multiple partners involved in cell signalling reactions and validated the system using F actin networks subjected to myosin-based contraction. Expressed in cultured cells, the sensor-containing FLNA construct reproducibly reported FLNA domain unfolding strikingly localized to dynamic, actively protruding, leading cell edges. The unfolding signal depends upon coherence of F-actin-FLNA networks and is enhanced by stimulating cell contractility. The results establish protein domain distortion as a bona fide mechanism for mechanotransduction in vivo. PMID- 25120199 TI - The "tale" of poly(A) binding protein: the MLLE domain and PAM2-containing proteins. AB - The cytoplasmic poly(A) binding protein 1 (PABPC1) is an essential eukaryotic translational initiation factor first described over 40 years ago. Most studies of PABPC1 have focused on its N-terminal RRM domains, which bind the mRNA 3' poly(A) tail and 5' translation complex eIF4F via eIF4G; however, the protein also contains a C-terminal MLLE domain that binds a peptide motif, termed PAM2, found in many proteins involved in translation regulation and mRNA metabolism. Studies over the past decade have revealed additional functions of PAM2 containing proteins (PACs) in neurodegenerative diseases, circadian rhythms, innate defense, and ubiquitin-mediated protein degradation. Here, we summarize functional and structural studies of the MLLE/PAM2 interaction and discuss the diverse roles of PACs. PMID- 25120198 TI - Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury. AB - Maladaptive remodelling of the arterial wall after mechanical injury (e. g. angioplasty) is characterised by inflammation, neointima formation and media hypertrophy, resulting in narrowing of the affected artery. Moreover, mechanical injury of the arterial wall causes loss of the vessel protecting endothelial cell monolayer. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, regulates inflammation, cell migration and proliferation, essential processes for vascular remodelling and re endothelialisation. Therefore, we investigated the role of MK2 in remodelling and re-endothelialisation after arterial injury in genetically modified mice in vivo. Hypercholesterolaemic low-density-lipoprotein-receptor-deficient mice (ldlr-/-) were subjected to wire injury of the common carotid artery. MK2-deficiency (ldlr /-/mk2-/-) nearly completely prevented neointima formation, media hypertrophy, and lumen loss after injury. This was accompanied by reduced proliferation and migration of MK2-deficient smooth muscle cells. In addition, MK2-deficiency severely reduced monocyte adhesion to the arterial wall (day 3 after injury, intravital microscopy), which may be attributed to reduced expression of the chemokine ligands CCL2 and CCL5. In line, MK2-deficiency significantly reduced the content of monocytes, neutrophiles and lymphocytes of the arterial wall (day 7 after injury, flow cytometry). In conclusion, in a model of endothelial injury (electric injury), MK2-deficiency strongly increased proliferation of endothelial cells and improved re-endothelialisation of the arterial wall after injury. Deficiency of MK2 prevents adverse remodelling and promotes endothelial healing of the arterial wall after injury, suggesting that MK2-inhibition is a very attractive intervention to prevent restenosis after percutaneous therapeutic angioplasty. PMID- 25120201 TI - Wilson's disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment. AB - OBJECTIVE: To describe characteristics of REM sleep behavior disorder in Wilson's disease. METHOD: Questionnaire-based interviews (patients and relatives), neurological examinations, two-week prospective dream-diary, video polysomnography, transcranial sonography, MRI. RESULTS: Four Wilson's disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. CONCLUSION: This first description of REM sleep behavior disorder in Wilson's disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson's disease and adds further evidence to the parallelism of Parkinson's disease and Wilson's disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in alpha synucleinopathies. In Wilson's disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson's disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in "pre-clinical" Parkinson's disease. PMID- 25120202 TI - Electroencephalographic and behavioral effects of intracerebroventricular or intraperitoneal injections of toxic honey extract in adult Wistar rats and GAERS. AB - Toxic honey, containing grayanotoxin, is obtained from nectar and polen of rhododendron. Consumed in excess it produces seizures and convulsions. In order to investigate whether the toxic honey extract can be used as a seizure model, we examined the electroencephalographic (EEG) and motor effects of intracerebroventricular (icv) or intraperitoneal (ip) injection of toxic honey extract in Wistar rats or in genetic absence epilepsy rats from Strasbourg (GAERS). Male Wistar rats or GAERS were stereotaxically implanted with bilateral cortical recording electrodes in all ip groups and cannula in the icv groups. Based on the previous study, an extract was obtained from the non-toxic and toxic honey. After the injection of the non-toxic or toxic honey extract, seizure stages and changes in EEG were evaluated from 9 am to noon. The icv administration of toxic honey extract produced stage 4 seizures and bilateral cortical spikes within 30-60 min and these effects disappeared after 120 min in Wistar rats or GAERS. The mean of bilateral cortical spike acitivity in EEG of Wistar rats was 804.2 +/- 261.0 s in the 3-h period. After the icv administration of toxic honey extract to GAERS, the mean duration of spike-and-wave discharges (SWDs) in GAERS significantly decreased during the first 60 min and then returned to baseline level. Ip injection of toxic honey extract caused no seizure and no change in EEG in either GAERS or Wistars. These results suggest that the icv administration of toxic honey extract can be used as a seizure model. PMID- 25120200 TI - Improving outcomes for youth with ADHD: a conceptual framework for combined neurocognitive and skill-based treatment approaches. AB - Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and chronic mental health condition that often results in substantial impairments throughout life. Although evidence-based pharmacological and psychosocial treatments exist for ADHD, effects of these treatments are acute, do not typically generalize into non treated settings, rarely sustain over time, and insufficiently affect key areas of functional impairment (i.e., family, social, and academic functioning) and executive functioning. The limitations of current evidence-based treatments may be due to the inability of these treatments to address underlying neurocognitive deficits that are related to the symptoms of ADHD and associated areas of functional impairment. Although efforts have been made to directly target the underlying neurocognitive deficits of ADHD, extant neurocognitive interventions have shown limited efficacy, possibly due to misspecification of training targets and inadequate potency. We argue herein that despite these limitations, next generation neurocognitive training programs that more precisely and potently target neurocognitive deficits may lead to optimal outcomes when used in combination with specific skill-based psychosocial treatments for ADHD. We discuss the rationale for such a combined treatment approach, prominent examples of this combined treatment approach for other mental health disorders, and potential combined treatment approaches for pediatric ADHD. Finally, we conclude with directions for future research necessary to develop a combined neurocognitive + skill-based treatment for youth with ADHD. PMID- 25120203 TI - Study of proximal femoral bone perfusion with 3D T1 dynamic contrast-enhanced MRI: a feasibility study. AB - OBJECTIVE: The objective of this study was to compare measurements of semi quantitative and pharmacokinetic parameters in areas of red (RBM) and yellow bone marrow (YBM) of the hip, using an in-house high-resolution DCE T1 sequence, and to assess intra- and inter-observer reproducibility of these measurements. METHODS: The right hips of 21 adult patients under 50 years of age were studied. Spatial resolution was 1.8 * 1.8 * 1.8 mm(3), and temporal resolution was 13.5 seconds. Two musculoskeletal radiologists independently processed DCE images and measured semi-quantitative and pharmacokinetic parameters in areas of YBM and RBM. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated. Intra- and inter-observer reproducibility was assessed. RESULTS: Area under the curve (AUC) and initial slope (IS) were significantly greater for RBM than for YBM (p < 0.05). K(trans) and kep were also significantly greater for RBM (p < 0.05). There was no significant difference in time to peak between the regions (p < 0.05). SNR, CNR, and intra- and inter-observer reproducibility were all good. CONCLUSIONS: DCE study of the whole hip is feasible with high spatial resolution using a 3D T1 sequence. Measures were possible even in low vascularized areas of the femoral head. K(trans), kep, AUC, and IS values were significantly different between red and yellow marrow, whereas TTP values were not. KEY POINTS: High spatial-resolution dynamic contrast-enhanced MRI of hip structures is feasible. Intra- and inter-observer reproducibility is good. Red and yellow bone marrow have different perfusion patterns. PMID- 25120204 TI - Anatomic variants of the pancreatic duct and their clinical relevance: an MR guided study in the general population. AB - OBJECTIVES: To investigate the frequency of pancreatic duct (PD) variants and their effect on pancreatic exocrine function in a population-based study using non-invasive secretin-stimulated magnetic resonance cholangiopancreatography (sMRCP). METHODS: Nine hundred and ninety-five volunteers, 457 women and 538 men, aged 51.9 +/- 13.4 years, underwent navigator-triggered, T2-weighted, 3D turbo spin echo MRCP on a 1.5 T system after 1 unit/kg secretin administration. Two readers evaluated images for PD variants. Pancreatic exocrine function and morphological signs of chronic pancreatitis such as abnormalities of the main PD, side branch dilatation, and pancreatic cysts were evaluated and related to PD variants using a Kruskal-Wallis test and post hoc analysis. RESULTS: Of all sMRCP, 93.2% were of diagnostic quality. Interobserver reliability for detection of PD variants was found to be kappa 0.752 (95 %CI, 0.733 - 0.771). Normal PD variants were observed in 90.4% (n = 838/927). Variants of pancreas divisum was identified in 9.6% (n = 89/927). Abnormalities of the main PD, side branch dilatation, and pancreatic cysts were observed in 2.4%, 16.6%, and 27.7%, respectively, and were not significantly different between pancreas divisum and non-divisum group (P = 0.122; P = 0.152; P = 0.741). There was no association between PD variants and pancreatic exocrine function (P = 0.367). CONCLUSION: PD variants including pancreas divisum are not associated with morphological signs of chronic pancreatitis or restriction of pancreatic exocrine function. KEY POINTS: MRCP allows the evaluation of pancreatic duct variants and morphological change. Pancreatic duct variants are not associated with morphological signs of chronic pancreatitis. Pancreas divisum is not accompanied by restriction of pancreatic exocrine function. Pancreatic duct variants including pancreas divisum are limited in their clinical relevance. PMID- 25120205 TI - Differentiation of focal nodular hyperplasia from hepatocellular adenomas with low-mechanical-index contrast-enhanced sonography (CEUS): effect of size on diagnostic confidence. AB - PURPOSE: The purpose of this study was to assess the diagnostic performance of contrast-enhanced sonography (CEUS) for the differentiation of focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA) according to lesion size. MATERIALS AND METHODS: Forty patients with a definite diagnosis of FNH or HCA who underwent CEUS were included in this institutional review board (IRB)-approved study. A total of 43 FNHs and 20 HCAs, including 15 inflammatory HCAs and five unclassified HCAs, were analysed. Two radiologists reviewed the diagnostic CEUS parameters separately and in consensus, including the presence or absence of centrifugal filling and central vessels. The sensitivity (Se), specificity (Sp), and inter-observer confidence (Kappa) of CEUS diagnostic parameters were assessed. RESULTS: Inter-observer agreement of CEUS for FNH diagnosis was high (kappa = 0.81) with an overall Se of 67.4% [29/43 (CI 95%: 51.4-80.1 %)] and an Sp of 100% [20/20 (CI 95%: 81-100%)]. Significantly higher Se figures were found for lesions <= 35 mm than for lesions > 35 mm [respectively, 93 % (28/30) (CI 95%: 77.6-99.2) vs. 7.7% (1/13) (CI 95%: 0.2-36%), p = 0.002] with unchanged specificity. CONCLUSION: CEUS is highly specific for the diagnosis of FNH, with very good inter-observer agreement, whatever the size, but its sensitivity is significantly reduced in diagnosing lesions larger than 35 mm. KEY POINTS: * CEUS is highly specific for the diagnosis of FNH, regardless of lesion size * CEUS shows reduced sensitivity in diagnosing FNH lesions larger than 35 mm * The filling patterns of hepatocellular adenomas are not affected by lesion size. PMID- 25120208 TI - Synthesis and structures of tris(2-pyridyl)aluminate sandwich compounds [{RAl(2 py')2}2M] (py' = 2-pyridyl, M = Ca, Mn, Fe). AB - Reactions of the lithium salts [{RAl(2-py')3Li.THF] [2-py' = 2-py (2-pyridyl), R = (n)Bu (1), R = (sec)Bu (2); py' = 5-Me-2-py (5-methyl-2-pyridyl), R = Me (3); 6 Me-2-py (6-methyl-2-pyridyl), R = Et (4b)] with the corresponding metal(ii) halides give the new heterobimetallic sandwich compounds [{RAl(2-py)3}2M] [R = (n)Bu, M = Ca (5), Mn (6), Fe (7); R = (sec)Bu, M = Ca (8), Mn (9)], [{MeAl(5-Me 2-py)3}2Ca] (10) and [{EtAl(6-Me-2-py)3}2Ca] (11) and the co-complex [{EtAl(6-Me 2-py)3}Mn(MU-Cl)Li{(6-Me-2-py)3AlEt}] (12). While neither the bridgehead group (R) nor remote ring Me-groups have any impact on metal coordination in 5-10, the introduction of Me groups into the pyridyl substituent at the 6-position (i.e., adjacent to the donor pyridyl-N atoms) has a marked effect on the ability of the ligands to form sandwich arrangements, as seen in the distorted structure of the sandwich compound 11 and in the formation of the co-complex 12, consisting of a two half-sandwich arrangement linked by a MU-Cl ion. The syntheses and solid state structures of the new precursor 4b and the new compounds 5-12 are reported. PMID- 25120206 TI - Correlations of (18)F-fluorothymidine uptake with pathological tumour size, Ki-67 and thymidine kinase 1 expressions in primary and metastatic lymph node colorectal cancer foci. AB - OBJECTIVE: To examine correlations of (18)F-fluorothymidine (FLT) uptake with pathological tumour size and immunohistochemical Ki-67, and thymidine kinase 1 (TK-1) expressions in primary and metastatic node colorectal cancer foci. METHODS: Thirty primary cancers (PCs) and 37 metastatic nodes (MNs) were included. FLT uptake was assessed by visual scores (non-visible: 0-1 and visible: 2-4), standardized uptake value (SUV), and correlated with size, Ki-67, and TK-1. SUV was measured in visible lesions. FLT heterogeneity was assessed by visual scores (no heterogeneous uptake: 0 and heterogeneous uptake: 1-4). RESULTS: Forty two lesions were visible. The visible group showed significantly higher values than the non-visible group in size, Ki-67, and TK-1 (each p < 0.05). Size correlated significantly with visual score (PC; rho = 0.74 and MN; rho = 0.63), SUVmax (PC; rho = 0.49, and MN; rho = 0.76), and SUVmean (PC; rho = 0.40 and MN; rho = 0.76) (each p < 0.05). Visual score correlated significantly with size (rho = 0.86), Ki-67max (rho = 0.35), Ki-67mean (rho = 0.38), TK-1max (rho = 0.35) and TK-1mean (rho = 0.25) (each p < 0.05). No significant correlations were found between FLT uptake and Ki-67 or TK-1 in 42 visible lesions (each p > 0.05). Heterogeneous FLT uptake was noted in 73 % (22/30) of PCs. CONCLUSION: FLT uptake correlated with size. Heterogeneous FLT distribution in colorectal cancers may be one of the causes of weak or lack of FLT uptake/Ki-67 or TK-1 correlation. KEY POINTS: FLT uptake correlated well with tumour size in colorectal cancer. Weak or lack of FLT uptake/Ki-67 and TK-1 correlations were observed. Immunohistochemical Ki-67 and TK-1 expressions are not always correlated with FLT uptake. PMID- 25120207 TI - Non-invasive biomechanical characterization of intervertebral discs by shear wave ultrasound elastography: a feasibility study. AB - OBJECTIVES: Although magnetic resonance is widely spread to assess qualitatively disc morphology, a simple method to determine reliably intervertebral disc status is still lacking. Shear wave elastography is a novel technique that allows quantitative evaluation of soft-tissues' mechanical properties. The aim of this study was to assess preliminary the feasibility and reliability of mechanical characterization of cervical intervertebral discs by elastography and to provide first reference values for asymptomatic subjects. METHODS: Elastographic measurements were performed to determine shear wave speed (SWS) in C6-C7 or C7-T1 disc of 47 subjects; repeatability and inter-operator reproducibility were assessed. RESULTS: Global average shear wave speed (SWS) was 3.0 +/- 0.4 m/s; measurement repeatability and inter-user reproducibility were 7 and 10%, respectively. SWS was correlated with both subject's age (p = 1.3 * 10(-5)) and body mass index (p = 0.008). CONCLUSIONS: Shear wave elastography in intervertebral discs proved reliable and allowed stratification of subjects according to age and BMI. Applications could be relevant, for instance, in early detection of disc degeneration or in follow-up after trauma; these results open the way to larger cohort studies to define the place of this technique in routine intervertebral disc assessment. KEY POINTS: A simple method to obtain objectively intervertebral disc status is still lacking. Shear wave elastography was applied in vivo to assess intervertebral discs. Elastography showed promising results in biomechanical disc evaluation. Elastography could be relevant in clinical routine for intervertebral disc assessment. PMID- 25120209 TI - Targeting the PI3K/Akt pathway in prostate cancer: challenges and opportunities (review). AB - The PI3K/Akt pathway is an actively pursued therapeutic target in oncology. In prostate cancer, the activation of this pathway appears to be characteristic of many aggressive prostate cancers. Further, activation of the PI3K/Akt pathway is more frequently observed as prostate cancer progresses toward a resistant, metastatic disease. Signalling from this pathway activates numerous survival, growth, metabolic and metastatic functions characteristic of aggressive cancer. Biomarkers of this pathway have correlated activation of this pathway to high grade disease and higher risk of disease progression. Therefore there is significant interest in developing effective strategies to target this pathway in prostate cancer. In this review, we discuss the pre-clinical and clinical data relevant to targeting of the PI3K/Akt pathway in prostate cancer. In particular, we review the rationale and relevance of co-targeting approaches against the PI3K/Akt pathway. It is anticipated that through an improved understanding of the biology of the PI3K/Akt pathway in prostate cancer, relevant biomarkers and rationale combination therapies will optimize targeting of this pathway to improve outcomes among patients with aggressive prostate cancer. PMID- 25120210 TI - Mapping central alpha-helix linker mediated conformational transition pathway of calmodulin via simple computational approach. AB - The effects of intrinsic structural flexibility of calmodulin protein on the mechanism of its allosteric conformational transition are investigated in this article. Using a novel in silico approach, the conformational transition pathways of intact calmodulin as well as the isolated N- and C- terminal domains are identified and energetically characterized. It is observed that the central alpha helix linker amplifies the structural flexibility of intact Ca(2+)-free calmodulin, which might facilitate the transition of the two domains. As a result, the global conformational transition of Ca(2+)-free calmodulin is initiated by the barrierless transition of two domains and proceeds through the barrier associated unwinding and bending of the central alpha-helix linker. The binding of Ca(2+) cations to calmodulin further increases the structural flexibility of the C-terminal domain and results in a downhill transition pathway of which all regions transit in a concerted manner. On the other hand, the separation of the N- and C-terminal domains from calmodulin protein loses the mediating function of central alpha-helix linker, leading to more difficult conformational transitions of both domains. The present study provides novel insights into the correlation of the integrity of protein, the structural flexibility, and the mechanism of conformational transition of proteinlike calmodulin. PMID- 25120211 TI - Perioperative cardiovascular complications versus perioperative bleeding in consecutive patients with known cardiac disease undergoing non-cardiac surgery. Focus on antithrombotic medication. The PRAGUE-14 registry. AB - BACKGROUND: Interruption of antithrombotic treatment before surgery may prevent bleeding, but at the price of increasing cardiovascular complications. This prospective study analysed the impact of antithrombotic therapy interruption on outcomes in non-selected surgical patients with known cardiovascular disease (CVD). METHODS: All 1200 consecutive patients (age 74.2 +/- 10.2 years) undergoing major non-cardiac surgery (37.4 % acute, 61.4 % elective) during a period of 2.5 years while having at least one CVD were enrolled. Details on medication, bleeding, cardiovascular complications and cause of death were registered. RESULTS: In-hospital mortality was 3.9 % (versus 0.9 % mortality among 17,740 patients without CVD). Cardiovascular complications occurred in 91 (7.6 %) patients (with 37.4 % case fatality). Perioperative bleeding occurred in 160 (13.3 %) patients and was fatal in 2 (1.2 % case fatality). Multivariate analysis revealed age, preoperative anaemia, history of chronic heart failure, acute surgery and general anaesthesia predictive of cardiovascular complications. For bleeding complications multivariate analysis found warfarin use in the last 3 days, history of hypertension and general anaesthesia as independent predictive factors. Aspirin interruption before surgery was not predictive for either cardiovascular or for bleeding complications. CONCLUSIONS: Perioperative cardiovascular complications in these high-risk elderly all-comer surgical patients with known cardiovascular disease are relatively rare, but once they occur, the case fatality is high. Perioperative bleeding complications are more frequent, but their case fatality is extremely low. Patterns of interruption of chronic aspirin therapy before major non-cardiac surgery are not predictive for perioperative complications (neither cardiovascular, nor bleeding). Simple baseline clinical factors are better predictors of outcomes than antithrombotic drug interruption patterns. PMID- 25120212 TI - Prognostic value of microvolt T-wave alternans in a real-world ICD population. Twente ICD Cohort Studie (TICS). AB - INTRODUCTION: Survival benefit from ICD implantation is relatively low in primary prevention patients. Better patient selection is important to maintain maximum survival benefit while reducing the number of unnecessary implants. Microvolt T wave alternans (MTWA) is a promising risk marker. In this study, we aimed to evaluate the predictive value of MTWA in ICD patients. METHODS AND RESULTS: This study was a substudy of the Twente ICD Cohort Study (TICS). Patients with ischaemic or non-ischaemic left ventricular dysfunction who received an ICD following current ESC guidelines were eligible for inclusion. Exercise-MTWA was performed and classified as non-negative or negative. The primary endpoint was the composite of mortality and appropriate shock therapy. Analysis was performed in 134 patients (81 % male, mean age 62 years, mean ejection fraction 26.5 %). MTWA was non-negative in 64 %. There was no relation between non-negative MTWA testing and mortality and/or appropriate shock therapy (all p-values >0.15). Due to clinical conditions, 24 % were ineligible for testing. These patients experienced the highest risk for mortality (p < 0.01). CONCLUSION: Non-negative MTWA testing did not predict mortality and/or appropriate shock therapy. Furthermore, MTWA testing is not feasible in a large percentage of patients. These ineligible patients experience the highest risk for mortality. PMID- 25120213 TI - Trait mindfulness and autobiographical memory specificity. AB - Training in mindfulness skills has been shown to increase autobiographical memory specificity. The aim of this study was to examine whether there is also an association between individual differences in trait mindfulness and memory specificity using a non-clinical student sample (N = 70). Also examined were the relationships between other memory characteristics and trait mindfulness, self reported depression and rumination. Participants wrote about 12 autobiographical memories, which were recalled in response to emotion word cues in a minimal instruction version of the Autobiographical Memory Test, rated each memory for seven characteristics, and completed the Freiburg Mindfulness Inventory, the Depression, Anxiety, and Stress Scale, and the Ruminative Responses Scale. Higher rumination scores were associated with more reliving and more intense emotion during recall. Depression scores were not associated with any memory variables. Higher trait mindfulness was associated with lower memory specificity and with more intense and more positive emotion during recall. Thus, trait mindfulness is associated with memory specificity, but the association is opposite to that found in mindfulness training studies. It is suggested that this difference may be due to an influence of trait mindfulness on memory encoding as well as retrieval processes and an influence on the mode of self-awareness that leads to a greater focus on momentary rather than narrative self-reference. PMID- 25120215 TI - Can immunostimulants efficiently replace antibiotic in striped catfish (Pangasianodon hypophthalmus) against bacterial infection by Edwardsiella ictaluri? AB - The present study was performed to determine the efficacy of lipopolysaccharide (LPS) and levamisole on immune response and disease resistance in striped catfish and to compare their respective efficiency with the one of an antibiotic treatment after infection of fish by the bacteria Edwardsiella ictaluri. Fish were divided into 3 groups and each group was injected with LPS (3 mg/kg fish), levamisole (5 mg/kg fish) or phosphate buffer saline as control. At day 21st post immunostimulant injection, fish were bled for assaying immunological variables and then challenged with E. ictaluri. Three days after bacterial infection, an antibiotic treatment was applied into fish subgroups and mortality was compared daily between antibiotic treated and untreated fish until 2 weeks post-challenge. LPS and levamisole significantly enhanced non-specific immune responses such as respiratory burst, lysozyme and complement activity in fish compared with control (p < 0.05). Respiratory burst and complement activity significantly increased in levamisole groups when compared with LPS groups while lysozyme activity did not differ significantly between immunostimulant treatments. Total immunoglobulins significantly increased in levamisole treatment compared with control. After challenge test, accumulated mortality was reduced significantly in both non antibiotic and antibiotic subgroups of LPS and levamisole compared with control. Moreover, no differences of mortality were observed between fish treated with levamisole or LPS without antibiotics and control fish treated with antibiotics. These results support the possible replacement of antibiotics in striped catfish farming by immunostimulants such as levamisole and LPS. PMID- 25120214 TI - Epidermal growth factor receptor and KRAS mutations in lung adenocarcinoma: a retrospective study of the Lebanese population. AB - Molecular genetic analysis of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) mutations in lung adenocarcinoma has become an integral part of lung cancer diagnosis and treatment; however, their prevalence varies with ethnicity. Little is know concerning their prevalence in Arab populations. In the present study, mutational analysis for EGFR and KRAS was performed on two cohorts of the Lebanese population. Lung adenocarcinoma cases (106) underwent mutational analysis for KRAS in exon 2, codon 12 and 13 and exon 3 codon 61 by reverse hybridization using the KRAS 12/13/61 StripAssay(r). Subsequently, cases with no KRAS mutations underwent EGFR mutational analysis using the EGFR RGQ polymerase chain reaction (PCR) kits for real-time PCR on the Rotor-Gene Q 5-plex HRM. KRAS mutations were detected in 37.7% of 106 lung adenocarcinomas; 85% had a G>T substitution in codon 12 and 13 of exon 2, and 8.5% had EGFR mutations with exon 19 deletions (88.9%) and one case with L858R substitution in exon 21. EGFR mutations were significantly correlated with females, non-smokers and well differentiation of the tumor. This is the first study in an Arab population that reports the prevalence of both EGFR and KRAS gene mutations in lung adenocarcinoma using very sensitive mutational analysis techniques. Therefore, EGFR reflex testing should be implemented in the management of lung adenocarcinomas, while KRAS testing must await the identification of effective targeted therapy. PMID- 25120216 TI - Characteristic and functional analysis of a ficolin-like protein from the oyster Crassostrea hongkongensis. AB - Ficolins are a group of soluble animal proteins with multiple roles in innate immunity. These proteins recognize and bind carbohydrates in pathogens and activate the complement system, leading to opsonization, leukocyte activation, and direct pathogen killing, which have been reported in many animal species but might not be present in the shellfish lineage. In the present study, we identified the first fibrinogen-related protein from the oyster, Crassostrea hongkongensis. This novel ficolin-like protein contains a typical signal peptide and a fibrinogen-related domain (designated ChFCN) at the N and C termini, respectively, but does not contain the additional collagen-like domain of ficolins. The full-length cDNA of ChFCN is 1105 bp, encoding a putative protein of 297 amino acids with the molecular weight of 35.5 kD. ChFCN is ubiquitously expressed in selected tissues, with the highest expression level observed in the gills. The temporal expression of ChFCN following microbe infection shows that the expression of ChFCN in hemocytes increases at 3 h post-challenge. The ChFCN protein expression was also examined, and fluorescence microscopy revealed that deChFCN (truncated signal peptide) is located in the cytoplasm of HeLa cells. Full-length ChFCN was detected in the medium supernatant by western blot analysis. Recombinant ChFCN proteins with the molecular weight about 50 kD bind Saccharomyces cerevisiae, Staphylococcus haemolyticus or Escherichia coli K-12, but not those from Vibrio alginolyticus. Furthermore, the rChFCN protein could agglutinate Gram-negative bacteria E. coli K-12 and enhance the phagocytosis of C. hongkongensis hemocytes in vitro. These results indicate that ChFCN might play an important role in the immunity response of oysters. PMID- 25120217 TI - Molecular cloning and characterization of high mobility group box1 (Ls-HMGB1) from humphead snapper, Lutjanus sanguineus. AB - High mobility group box1 (HMGB1) is a kind of chromatin-associated nonhistone protein important for nucleosome formation, transcriptional regulation and inflammation. However, the reports about HMGB1 of marine fish were still limited. Here, we cloned and characterized a HMGB1 gene from humphead snapper, Lutjanus sanguineus (Ls-HMGB1). The Ls-HMGB1 cDNA composed of 1199 bp with a 70 bp of 5' UTR, 630 bp open reading frame (ORF) and 499 bp 3'-UTR, encoded a polypeptide of 210 amino acids (GenBank Accession No: KJ783442). Sequence alignment of Ls-HMGB1 showed the highest similarity of 91% with Sciaenops ocellatus HMGB1 protein. Quantitative real-time PCR (qRT-PCR) analysis revealed that Ls-HMGB1 had relatively high expression level in skin, kidney and heart. After Vibrio harveyi and poly I:C stimulation, transcripts of Ls-HMGB1 were significantly increased and reached to peak at 18 h p.i. The L. sanguineus interleukin-6 (Ls-IL6) transcription in HK leukocytes was significantly induced by recombinant LsHMGB1 (rLsHMGB1). These results indicated that Ls-HMGB1 may play an important role in immune response of L. sanguineus during pathogen challenge. PMID- 25120218 TI - N-acetylglucosamine enhances survival ability of tilapias infected by Streptococcus iniae. AB - Streptococcus iniae infection has emerged as a serious fish health and economic problem in the global aquaculture operations. Current antibiotic options are few and possess severe practical limitations and potential adverse environmental impacts. The major factor contributing to the large burden of S. iniae disease in aquaculture is the lack of fundamental knowledge of innate immunity against the pathogen. In the present study, we use a tilapia model to explore which metabolites are crucial for the defense against the infection caused by S. iniae. We establish GC/MS based metabolic profile of tilapia liver and then compare the metabolic difference between survivals and the dying fish post the bacterial infection. We identify elevating N-acetylglucosamine in survival group as the most crucial metabolite differentiating the survivals from the dying in these fish infected by S. iniae. Exogenous N-acetylglucosamine significantly elevates survival ability of tilapia against the infection caused by S. iniae. Our findings highlight the importance of metabolic strategy against bacterial infections. PMID- 25120219 TI - Inducible and constitutive expression of an elicitor gene Hrip1 from Alternaria tenuissima enhances stress tolerance in Arabidopsis. AB - Hrip1 is a novel hypersensitive response-inducing protein secreted by Alternaria tenuissima that activates defense responses and systemic acquired resistance in tobacco. This study investigates the role that Hrip1 plays in responses to abiotic and biotic stress using transgenic Arabidopsis thaliana expressing the Hrip1 gene under the control of the stress-inducible rd29A promoter or constitutive cauliflower mosaic virus 35S promoter. Bioassays showed that inducible Hrip1 expression in rd29A?Hrip1 transgenic lines had a significantly higher effect on plant height, silique length, plant dry weight, seed germination and root length under salt and drought stress compared to expression in 35S?Hrip1 lines and wild type plants. The level of enhancement of resistance to Botrytis cinerea by the 35S?Hrip1 lines was higher than in the rd29A?Hrip1 lines. Moreover, stress-related gene expression in the transgenic Arabidopsis lines was significantly increased by 200 mM NaCl and 200 mM mannitol treatments, and defense genes in the jasmonic acid and ethylene signaling pathway were significantly up-regulated after Botrytis inoculation in the Hrip1 transgenic plants. Furthermore, the activity of some antioxidant enzymes, such as peroxidase and catalase increased after salt and drought stress and Botrytis infection. These results suggested that the Hrip1 protein contributes to abiotic and biotic resistance in transgenic Arabidopsis and may be used as a useful gene for resistance breeding in crops. Although the constitutive expression of Hrip1 is suitable for biotic resistance, inducible Hrip1 expression is more responsive for abiotic resistance. PMID- 25120220 TI - A complex RARE is required for the majority of Nedd9 embryonic expression. AB - Neural precursor cell expressed, developmentally down-regulated 9 (Nedd9, Casl, Hef1, p105cas, Ef1) is a scaffolding protein that assembles complexes involved in regulating cell adhesion, migration, division, and survival. Nedd9 is found very early in the developing embryonic nervous system. A highly conserved complex retinoic acid response element (RARE) is located 485 base pairs (bp) upstream of exon 2B in the promoter of the Nedd9 gene. Mice transgenic for a 5.2 kilobase (kb) region of the 2B Nedd9 promoter containing the RARE upstream of a lacZ reporter gene [Nedd9(RARE)-lacZ] show a large subset of the normal endogenous Nedd9 expression including that in the caudal hindbrain neuroepithelium, spinal cord, dorsal root ganglia (drg) and migrating neural crest (ncc). However, the transgenic mice do not recapitulate the native Nedd9 expression pattern in presumptive rhombomeres (pr) 3 and 5 of the early hindbrain, the base of the neuroepithelium in the midbrain, nor the forebrain telencephalon. Thus, the 5.2 kb region containing the intact RARE drives a large subset of Nedd9 expression, with additional sequences outside of this region needed to define the full complement of expression. When the 5.2 kb construct is modified (eight point mutations) to eliminate responsiveness of the RARE to all-trans retinoic acid (atRA) [Nedd9(mutRARE)-lacZ], virtually all beta-galactosidase (beta-gal, lacZ) expression is lost. Exposure of Nedd9(RARE)-lacZ transgenic embryos to excess atRA at embryonic day 8.0 (E8.0) leads to rostral ectopic transgene expression within 6 h whereas the Nedd9(mutRARE)-lacZ mutant does not show this effect. Thus the RARE upstream of the Nedd9 2B promoter is necessary for much of the endogenous gene expression during early development as well as ectopic expression in response to atRA. PMID- 25120221 TI - Imaging spectrum of peritoneal carcinomatosis on FDG PET/CT. AB - Recognition of patterns has always been extremely important in cross-sectional imaging. Peritoneal involvement, both primary and as dissemination from abdominopelvic malignancies, is manifested in different forms, purely because of anatomical complexity. We studied series of peritoneal involvement by (18)F fluorodeoxyglucose positron-emission tomography/computed tomography fusion imaging and derived patterns of tracer uptake on maximum intensity projection and cross-sectional fusion images. PMID- 25120222 TI - PTP1B inhibitors for type 2 diabetes treatment: a patent review (2011 - 2014). AB - INTRODUCTION: Protein tyrosine phosphatase 1B (PTP1B) plays an important role in the negative regulation of insulin signal transduction pathway and has emerged as novel therapeutic strategy for the treatment of type 2 diabetes. PTP1B inhibitors enhance the sensibility of insulin receptor (IR) and have favorable curing effect for insulin resistance-related diseases. A large number of PTP1B inhibitors, either synthetic or isolated as bioactive agents from natural products, have developed and investigated for their ability to stimulate insulin signaling. AREAS COVERED: This review includes an updated summary (2011 - 2014) of PTP1B inhibitors that have been published in patent applications, with an emphasis on their chemical structure, mode of action and therapeutic outcomes. The usefulness of PTP1B inhibitors as pharmaceutical agents for the treatment of type 2 diabetes is also discussed. EXPERT OPINION: PTP1B inhibitors show beneficial effects to enhance sensibility of IR by restricting the activity of enzyme and have favorable curing effects. However, structural homologies in the catalytic domain of PTP1B with other protein tyrosine phosphatases (PTPs) like leukocyte common antigen-related, CD45, SHP-2 and T-cell-PTP present a challenging task of achieving selectivity. Thus, for therapeutic application of PTP1B inhibitors, highly selective molecules exhibiting desired effects without side effects are expected to find clinical application. PMID- 25120224 TI - Magnetic steering control of multi-cellular bio-hybrid microswimmers. AB - Bio-hybrid devices, which integrate biological cells with synthetic components, have opened a new path in miniaturized systems with the potential to provide actuation and control for systems down to a few microns in size. Here, we address the challenge of remotely controlling bio-hybrid microswimmers propelled by multiple bacterial cells. These devices have been proposed as a viable method for targeted drug delivery but have also been shown to exhibit stochastic motion. We demonstrate a method of remote magnetic control that significantly reduces the stochasticity of the motion, enabling steering control. The demonstrated microswimmers consist of multiple Serratia marcescens (S. marcescens) bacteria attached to a 6 MUm-diameter superparamagnetic bead. We characterize their motion and define the parameters governing their controllability. We show that the microswimmers can be controlled along two-dimensional (2-D) trajectories using weak magnetic fields (<=10 mT) and can achieve 2-D swimming speeds up to 7.3 MUm s(-1). This magnetic steering approach can be integrated with sensory-based steering in future work, enabling new control strategies for bio-hybrid microsystems. PMID- 25120223 TI - Disruption of resting functional connectivity in Alzheimer's patients and at-risk subjects. AB - The resting brain exhibits continuous intrinsic activity, which is correlated between groups of regions forming resting state networks. Evaluating resting connectivity is a popular approach for studying brain diseases. Several hundred studies are now available that address integrity of resting connectivity in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), as well as preclinical at-risk subjects. Most studies focus on the default mode network, a system of specific brain areas showing strong connected resting activity that attenuates during goal-directed behavior. The extent of intrinsic brain activity tends to be strongly correlated with cognitive processes and is specifically disrupted in AD and MCI patients and at-risk subjects, with changes seeming to evolve during the transition between the disease stages. In this study, we review the current findings in default mode network and other resting state network studies in AD and MCI patients and at-risk subjects as assessed by resting state functional magnetic resonance imaging. PMID- 25120225 TI - Fast and mild strategy, using superhydrophobic surfaces, to produce collagen/platelet lysate gel beads for skin regeneration. AB - Platelet lysate (PL) was encapsulated in collagen (Coll) millimetric gel beads, on biomimetic superhydrophobic surfaces, under mild conditions, with the aim of obtaining easy-to-handle formulations able to provide sustained release of multiple growth factors for skin ulcers treatment. The gel particles were prepared with various concentrations of PL incorporating or not stem cells, and tested as freshly prepared or after being freeze-dried or cryopreserved. Coll + PL particles were evaluated regarding degradation in collagenase-rich environment (simulating the aggressive environment of the chronic ulcers), sustained release of total protein, PDGF-BB and VEGF, cell proliferation (using particles as the only source of growth factors), scratch wound recovery and angiogenic capability. Compared to Coll solely particles, incorporation of PL notably enhanced cell proliferation (inside and outside gels) and favored scratch wound recovery and angiogenesis. Moreover, cell-laden gel particles containing PL notably improved cell proliferation and even migration of cells from one particle towards a neighbor one, which led to cell-cell contacts and the spontaneous formation of tissue layers in which the spherical gels were interconnected by the stem cells. PMID- 25120228 TI - Perceptions of mailed HPV self-testing among women at higher risk for cervical cancer. AB - Whether human papillomavirus (HPV) self-testing can expand access to cervical cancer screening will depend on making the test accessible and acceptable to higher-risk women. To evaluate a novel delivery mode, we mailed HPV self-test kits to low-income, under-screened women and assessed their perceptions of self testing and cervical cancer prevention. We conducted a telephone survey of 199 women in North Carolina. Eligibility criteria included not having had a Pap test in 4 years and reporting 1 or more indicators of economic hardship, such as being uninsured. Over half (55 %) of women in the diverse sample were non-Hispanic black, and almost three-quarters (74 %) reported annual household incomes of $20,000 or less. Trust in HPV self-testing was moderate to high, with almost all women (98 %) agreeing the mailed test was safe. A few women (6 %) preferred HPV self-testing to Pap testing for protecting health, but most (75 %) had no preference. Trust in or preference for mailed self-testing did not vary by race or income. However, compared to white women, black women had lower HPV-related knowledge (OR 0.46, 95 % CI 0.23-0.92) and perceived lower cervical cancer risk in the absence of screening (OR 0.44, 95 % CI 0.22-0.86). We found similar patterns of disparities for women with very low (<$10,000) versus relatively higher incomes. Our findings suggest that, across racial and economic subgroups, under-screened women generally trust HPV self-tests delivered by mail. To succeed, programs for HPV self-testing must overcome disparities in knowledge and perceptions related to cervical cancer screening. PMID- 25120229 TI - Evaluation of the National HIV Behavioral Surveillance System among men who have sex with men in Denver, Colorado. AB - Denver Public Health implements the National HIV Behavioral Surveillance System (NHBS), a cyclical survey of populations at increased risk for HIV. We evaluated the implementation of NHBS among Denver men who have sex with men (MSM), considering the system's simplicity, data quality, representativeness, and sensitivity to trends. We found that the time required for implementation and the complexity of data management and analysis are barriers to disseminating local findings. Data quality has improved in each cycle of the study but must be protected by continually checking for errors and training field staff to be attentive to detail. Compared with the US census and other convenience samples of Denver MSM, the overall demographic representativeness of NHBS has improved over time. However, there is concern that the underlying population included in the study may be changing. NHBS survey data show evidence of two suspected trends in the local MSM population at risk for HIV: increasing sexual risk-taking and the transition away from bars as a dominant partner-finding location. It is unclear whether the increasing reports of sexual risk-taking reflect a real trend or simply a change in the population sampled, since most NHBS participants are recruited at gay bars and other venues. To ensure that the sample continues to represent the underlying population at risk and accurately identify trends, it is necessary to closely monitor MSM sample characteristics during implementation and incorporate weighted data provided by the Centers for Disease Control and Prevention into analyses. PMID- 25120230 TI - Medication use in community-residing older adults in Taiwan: a comparison between conventional and complementary and alternative medications. AB - Older adults are at risk of problems of medication use including underuse, overuse, and misuse. The purposes of this study were to investigate the prevalence of the use of conventional and complementary and alternative medications (CAM) in older adults and to explore which factors related to their medication use. For this descriptive correlational study, 1,427 citizens who were 65 years old or older from two towns in Yilan County, Taiwan were interviewed by ten trained public health nurses between June and September, 2013. Instruments in this study were physical functional capacity, depressive symptoms, and medication use. Pearson product-moment correlation analysis and the Chi-square test were used to detect relationships among research variables. Of the 1,427 participants, 75.4 % used at least one type of conventional medication, and the average number of medications used was 2.9 (SD = 2.1). Polypharmacy (the use of five or more medications) was identified in 20.1 % of participants. Significant factors related to conventional medications use were older age (chi(2) = 41.7***), female (chi(2) = 7.6**), bad memory (chi(2) = 11.2**), defect cognition status (chi(2) = 7.8**), lost the interest to do anything depressive symptoms (chi(2) = 7.2**), and independent in their daily activities (chi(2) = 41.3***). We found that sociodemographic characteristics and factors pertaining to health status determine the difference between the use of conventional medications and CAM by rural older adults. Our study results suggested that health professionals in Taiwan must be educated and trained in how to integrate CAM into current conventional treatment. PMID- 25120227 TI - A review of OROS methylphenidate (Concerta((r))) in the treatment of attention deficit/hyperactivity disorder. AB - Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioural disorder with onset during childhood. It affects a child's development, both at home and at school, and impacts on social, emotional and cognitive functioning, in both the home and the school environment. Untreated ADHD is very often associated with poor academic achievement, low occupational status, increased risk of substance abuse and delinquency. Current practice guidelines recommend a multimodal approach in the treatment of ADHD, which includes educational, behavioural and mental health interventions, and pharmacological management. Stimulant medications, including methylphenidate (MPH) and amphetamine products, are recommended as first-line pharmacotherapy in the treatment of ADHD. The choice of stimulant is influenced by several factors; the most influential factor is the duration of action. Long-acting medication provides benefits long after school and work. It also increases the likelihood of once-daily dosing, thereby eliminating the need for mid-day dosing, making the treatment more private, avoiding stigma and improving adherence to medication. MPH is the most widely used psychotropic medication in child psychiatry. It was first developed for use in children as an oral, immediate-release formulation and more recently as various extended-release formulations. These latter formulations include the 12 h preparation Concerta((r)) (osmotic-release oral system [OROS] MPH), which utilizes an osmotic pump system, designed to overcome the difficulties of multiple daily dosing. Since it received approval from the US Food and Drug Administration in August 2000, OROS MPH has been quickly and widely accepted as one of the preferred treatments for ADHD because of its once-daily dosing. This paper reviews the data in support of long-acting OROS MPH in children, adolescents and adults, both in ADHD and in association with its comorbidities. PMID- 25120226 TI - Human adipose-derived mesenchymal stem cells improve motor functions and are neuroprotective in the 6-hydroxydopamine-rat model for Parkinson's disease when cultured in monolayer cultures but suppress hippocampal neurogenesis and hippocampal memory function when cultured in spheroids. AB - Adult human adipose-derived mesenchymal stem cells (MSC) have been reported to induce neuroprotective effects in models for Parkinson's disease (PD). However, these effects strongly depend on the most optimal application of the transplant. In the present study we compared monolayer-cultured (aMSC) and spheroid (sMSC) MSC following transplantation into the substantia nigra (SN) of 6-OHDA lesioned rats regarding effects on the local microenvironment, degeneration of dopaminergic neurons, neurogenesis in the hippocampal DG as well as motor and memory function in the 6-OHDA-rat model for PD. aMSC transplantation significantly increased tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) levels in the SN, increased the levels of the glial fibrillary acidic protein (GFAP) and improved motor functions compared to untreated and sMSC treated animals. In contrast, sMSC grafting induced an increased local microgliosis, decreased TH levels in the SN and reduced numbers of newly generated cells in the dentate gyrus (DG) without yet affecting hippocampal learning and memory function. We conclude that the neuroprotective potential of adipose-derived MSC in the rat model of PD crucially depends on the applied cellular phenotype. PMID- 25120231 TI - Comparisons of tunnel-graft angle and tunnel length and position between transtibial and transportal techniques in anterior cruciate ligament reconstruction. AB - PURPOSE: Our aim was to evaluate tunnel-graft angle, tunnel length and position and change in graft length between transtibial (30 patients) and anteromedial (30 patients) portal techniques using 3D knee models after anterior cruciate ligament (ACL) reconstruction. METHODS: The 3D angle between femoral or tibial tunnels and graft at 0 degrees and 90 degrees flexion were compared between groups. We measured tunnel lengths and positions and evaluated the change in graft length from 0 degrees to 90 degrees flexion. RESULTS: The 3D angle at the femoral tunnel with graft showed a significant difference between groups at 0 degrees flexion (p = 0.01) but not at 90 degrees flexion (p = 0.12). The 3D angle of the tibial tunnel showed no significant differences between groups. Femoral tunnel length in the transtibial group was significantly longer than in the transportal group (40.7 vs 34.7 mm,), but tibial tunnel length was not. The relative height of the lateral femoral condyle was significantly lower in the transportal than the transtibial group (24.1% vs 34.4%). No significant differences were found between groups in terms of tibial tunnel position. The change in graft length also showed no significant difference between groups. CONCLUSION: Even though the transportal technique in ACL reconstruction can place the femoral tunnel in a better anatomical position than the transtibial technique, it has risks of a short femoral tunnel and acute angle at the femoral tunnel. Moreover, there was also no difference in the change of the graft length between groups. PMID- 25120232 TI - Full-thickness supraspinatus tendon tears: correlation of findings by arthroscopy and magnetic resonance imaging. AB - PURPOSE: The main aim of this study was to correlate measurements of the width and retraction of isolated full-thickness supraspinatus tendon tears determined by magnetic resonance imaging (MRI) with measurements recorded by arthroscopy using a continuous millimetre scale. METHODS: A total of 53 individuals with isolated supraspinatus tears and retraction < 30 mm underwent arthroscopy at our centre. Tear width and retraction measured by arthroscopy (reference standard) and MRI (index test) on a continuous millimetre scale were compared. All measurements were performed by a single radiologist blinded to intra-operative findings and one surgeon who had previous access to MRI results. RESULTS: The average tear retraction was 12.60 +/- 4.89 mm by arthroscopy and 16.81 +/- 6.29 mm by MRI. Those measures exhibited moderate correlation (r = 0.643, p < 0.001) and an average difference of 4.21 mm (p < 0.001). Average tear width was 12.87 +/ 4.15 mm by arthroscopy and 14.19 +/- 5.20 by MRI. Those measures exhibited moderate correlation (r = 0.526, p < 0.001) and an average difference of 1.32 mm, which was not statistically significant (p = 0.109). CONCLUSION: Measures of retraction and width obtained by MRI and arthroscopy exhibited moderate correlation in small- or medium-sized supraspinatus tears. PMID- 25120233 TI - Latent tuberculosis reactivation in a patient with erythrodermic psoriasis under treatment with ustekinumab and a low dose steroid, despite isoniazid chemoprophylaxis. PMID- 25120236 TI - Graph theoretical analysis on the kinetic rate equations of linear chain and cyclic reaction networks. AB - Graph theoretical solutions for kinetic rate equations of some reaction networks involving linear chains and cycles have been derived; condensation polymerization and long chain of radioactive decay come under the purview of the former whereas the interconversion of the species in cycles under the later. The reactions for the linear chains considered here proceed monotonically to the steady states with time whereas the cycle with all irreversible steps has been found to have either periodic or monotonic time evaluation of concentrations depending on the values of rate constants of the involved paths. In case of a cyclic reaction having all reversible paths, the condition for the microscopic reversibility has been derived on the basis of the assumption that the decay constants obtained for this case are all real. PMID- 25120235 TI - Ophthalmologic complications after intraoral local anesthesia. AB - INTRODUCTION: The first ophthalmologic complication in conjunction with a dental anesthesia was reported in 1936. The objective of the present study was a detailed analysis of case reports about that topic. MATERIAL AND METHODS: After conducting a literature search in PubMed this study analyzed 108 ophthalmologic complications following intraoral local anesthesia in 65 case reports with respect to patient-, anesthesia-, and complication- related factors. RESULTS: The mean age of the patients was 33.8 years and females predominated (72.3%). The most commonly reported complication was diplopia (39.8%), mostly resulting from paralysis of the lateral rectus muscle. Other relatively frequent complications included ptosis (16.7%), mydriasis (14.8%) and amaurosis (13%). Ophthalmologic complications were mainly associated with block anesthesia of the inferior alveolar nerve (45.8%) or the posterior superior alveolar nerve (40.3%). Typically, the ophthalmologic complications in conjunction with intraoral local anesthesia had an immediate to short onset, and disappeared as the anesthesia subsided. DISCUSSION AND CONCLUSION: The increased number of ophthalmologic complications after intraoral local anesthesia in females may suggest a gender effect. Double vision (diplopia) is the most frequently described complication, which is usually completely reversible like the other reported ophthalmologic complications. PMID- 25120234 TI - Sequencing, physical organization and kinetic expression of the patulin biosynthetic gene cluster from Penicillium expansum. AB - Patulin is a polyketide-derived mycotoxin produced by numerous filamentous fungi. Among them, Penicillium expansum is by far the most problematic species. This fungus is a destructive phytopathogen capable of growing on fruit, provoking the blue mold decay of apples and producing significant amounts of patulin. The biosynthetic pathway of this mycotoxin is chemically well-characterized, but its genetic bases remain largely unknown with only few characterized genes in less economic relevant species. The present study consisted of the identification and positional organization of the patulin gene cluster in P. expansum strain NRRL 35695. Several amplification reactions were performed with degenerative primers that were designed based on sequences from the orthologous genes available in other species. An improved genome Walking approach was used in order to sequence the remaining adjacent genes of the cluster. RACE-PCR was also carried out from mRNAs to determine the start and stop codons of the coding sequences. The patulin gene cluster in P. expansum consists of 15 genes in the following order: patH, patG, patF, patE, patD, patC, patB, patA, patM, patN, patO, patL, patI, patJ, and patK. These genes share 60-70% of identity with orthologous genes grouped differently, within a putative patulin cluster described in a non-producing strain of Aspergillus clavatus. The kinetics of patulin cluster genes expression was studied under patulin-permissive conditions (natural apple-based medium) and patulin-restrictive conditions (Eagle's minimal essential medium), and demonstrated a significant association between gene expression and patulin production. In conclusion, the sequence of the patulin cluster in P. expansum constitutes a key step for a better understanding of the mechanisms leading to patulin production in this fungus. It will allow the role of each gene to be elucidated, and help to define strategies to reduce patulin production in apple based products. PMID- 25120237 TI - Identification of atomic-level mechanisms for gas-phase X- + CH3Y SN2 reactions by combined experiments and simulations. AB - For the traditional model of gas-phase X(-) + CH3Y SN2 reactions, C3v ion-dipole pre- and postreaction complexes X(-)---CH3Y and XCH3---Y(-), separated by a central barrier, are formed. Statistical intramolecular dynamics are assumed for these complexes, so that their unimolecular rate constants are given by RRKM theory. Both previous simulations and experiments have shown that the dynamics of these complexes are not statistical and of interest is how these nonstatistical dynamics affect the SN2 rate constant. This work also found there was a transition from an indirect, nonstatistical, complex forming mechanism, to a direct mechanism, as either the vibrational and/or relative translational energy of the reactants was increased. The current Account reviews recent collaborative studies involving molecular beam ion-imaging experiments and direct (on-the-fly) dynamics simulations of the SN2 reactions for which Cl(-), F(-), and OH(-) react with CH3I. Also considered are reactions of the microsolvated anions OH(-)(H2O) and OH(-)(H2O)2 with CH3I. These studies have provided a detailed understanding of the atomistic mechanisms for these SN2 reactions. Overall, the atomistic dynamics for the Cl(-) + CH3I SN2 reaction follows those found in previous studies. The reaction is indirect, complex forming at low reactant collision energies, and then there is a transition to direct reaction between 0.2 and 0.4 eV. The direct reaction may occur by rebound mechanism, in which the ClCH3 product rebounds backward from the I(-) product or a stripping mechanism in which Cl(-) strips CH3 from the I atom and scatters in the forward direction. A similar indirect to direct mechanistic transition was observed in previous work for the Cl(-) + CH3Cl and Cl(-) + CH3Br SN2 reactions. At the high collision energy of 1.9 eV, a new indirect mechanism, called the roundabout, was discovered. For the F(-) + CH3I reaction, there is not a transition from indirect to direct reaction as Erel is increased. The indirect mechanism, with prereaction complex formation, is important at all the Erel investigated, contributing up ~60% of the reaction. The remaining direct reaction occurs by the rebound and stripping mechanisms. Though the potential energy curve for the OH(-) + CH3I reaction is similar to that for F(-) + CH3I, the two reactions have different dynamics. They are akin, in that for both there is not a transition from an indirect to direct reaction. However, for F(-) + CH3I indirect reaction dominates at all Erel, but it is less important for OH(-) + CH3I and becomes negligible as Erel is increased. Stripping is a minor channel for F(-) + CH3I, but accounts for more than 60% of the OH(-) + CH3I reaction at high Erel. Adding one or two H2O molecules to OH(-) alters the reaction dynamics from that for unsolvated OH(-). Adding one H2O molecule enhances indirect reaction at low Erel, and changes the reaction mechanism from primarily stripping to rebound at high Erel. With two H2O molecules the dynamics is indirect and isotropic at all collision energies. PMID- 25120238 TI - Anti-inflammatory effects of vitamin E on adjuvant-induced arthritis in rats. AB - Vitamin E (vit-E) is a lipophilic antioxidant, and its anti-inflammatory activity is still not full characterized. Thus, our goal was to investigate the anti inflammatory effect of repeated vit-E treatment in the arthritis induced by the intraplantar injection of complete Freund's adjuvant (CFA). We observed an increase in arthritis scores, interleukin-1beta and H2O2 levels, neutrophil and macrophage infiltration, thermal hyperalgesia, mechanical allodynia, and loss of function induced by intraplantar CFA injection. These effects were unaltered after 1 day, partially reversed after 3 days, and inhibited after 9 days after vit-E treatment. Furthermore, the concentration of vit-E was reduced and that of tumor necrosis factor-alpha was increased in the CFA-injected paw. Both effects were reversed from 1 to 9 days after vit-E treatment. However, vit-E treatment did not alter CFA-induced edema at any time. Thus, vit-E treatment produced an anti-inflammatory effect of slow onset in CFA, which demonstrates a disease modifying drug profile. PMID- 25120240 TI - Why does guessing incorrectly enhance, rather than impair, retention? AB - The finding that trying, and failing, to predict the upcoming to-be-remembered response to a given cue can enhance later recall of that response, relative to studying the intact cue-response pair, is surprising, especially given that the standard paradigm (e.g., Kornell, Hays, & Bjork, 2009) involves allocating what would otherwise be study time to generating an error. In three experiments, we sought to eliminate two potential heuristics that participants might use to aid recall of correct responses on the final test and to explore the effects of interference both at an immediate and at a delayed test. In Experiment 1, by intermixing strongly associated to-be-remembered pairs with weakly associated pairs, we eliminated a potential heuristic participants can use on the final test in the standard version of the paradigm-namely, that really strong associates are incorrect responses. In Experiment 2, by rigging half of the participants' responses to be correct, we eliminated another potential heuristic-namely, that one's initial guesses are virtually always wrong. In Experiment 3, we examined whether participants' ability to remember-and discriminate between-their incorrect guesses and correct responses would be lost after a 48-h delay, when source memory should be reduced. Across all experiments, we continued to find a robust benefit of trying to guess to-be-learned responses, even when incorrect, versus studying intact cue-response pairs. The benefits of making incorrect guesses are not an artifact of the paradigm, nor are they limited to short retention intervals. PMID- 25120241 TI - Testing can counteract proactive interference by integrating competing information. AB - Testing initially learned information before presenting new information has been shown to counteract the deleterious effects of proactive interference by segregating competing sources of information. The present experiments were conducted to demonstrate that testing can also have its effects in part by integrating competing information. Variations of classic A-B, A-D paired associate learning paradigms were employed that included two lists of word pairs and a cued-recall test. Repeated pairs appeared in both lists (A-B, A-B), control pairs appeared in List 2 only (A-B, C-D), and changed pairs appeared with the same cue in both lists but with different responses (A-B, A-D). The critical manipulation was whether pairs were tested or restudied in an interpolated phase that occurred between Lists 1 and 2. On a final cued-recall test, participants recalled List 2 responses and then indicated when they recollected that responses had earlier changed between lists. The change recollection measure indexed the extent to which competing responses were integrated during List 2. Change was recollected more often for tested than for restudied pairs. Proactive facilitation was obtained in cued recall when change was recollected, whereas proactive interference was obtained when change was not recollected. These results provide evidence that testing counteracted proactive interference in part by making List 1 responses more accessible during List 2, thus promoting integration and increasing later recollection of change. These results have theoretical implications because they show that testing can counteract proactive interference by integrating or segregating competing information. PMID- 25120242 TI - Getting completely turned around: how disorientation impacts subjective straight ahead. AB - In manipulating a pointer to indicate subjective straight ahead (SSA), participants were more variable after a series of whole-body rotations in conjunction with external sensory blockade than after external sensory blockade alone. The variability of reported SSA did not increase consequent to a temporal delay matched to the time taken by the rotation procedure. These results suggest that an observer's egocentric reference frame is more complex and less stable than has previously been thought. PMID- 25120239 TI - Protease-activated receptor 4: a critical participator in inflammatory response. AB - Protease-activated receptors (PARs) are G protein-coupled receptors of which four members PAR1, PAR2, PAR3, and PAR4 have been identified, characterized by a typical mechanism of activation involving various related proteases. The amino terminal sequence of PARs is cleaved by a broad array of proteases, leading to specific proteolytic cleavage which forms endogenous tethered ligands to induce agonist-biased PAR activation. The biological effect of PARs activated by coagulation proteases to regulate hemostasis and thrombosis plays an enormous role in the cardiovascular system, while PAR4 can also be activated by trypsin, cathepsin G, the activated factor X of the coagulation cascade, and trypsin IV. Irrespective of its role in thrombin-induced platelet aggregation, PAR4 activation is believed to be involved in inflammatory lesions, as show by investigations that have unmasked the effects of PAR4 on neutrophil recruitment, the regulation of edema, and plasma extravasation. This review summarizes the roles of PAR4 in coagulation and other extracellular protease pathways, which activate PAR4 to participate in normal regulation and disease. PMID- 25120243 TI - Revision laryngeal framework surgery performed by directly pulling the lateral cricoarytenoid muscle. AB - BACKGROUND: Revision laryngeal framework surgery is usually performed for medialisation laryngoplasty failure, rather than for failure after arytenoid adduction. We describe a new method for revision arytenoid adduction surgery, performed by directly pulling the lateral cricoarytenoid muscle ('lateral cricoarytenoid muscle pull surgery'). METHODS: We describe a case of revision laryngeal framework surgery, present a literature review and describe the advantages of lateral cricoarytenoid muscle pull surgery over the original method of arytenoid adduction using a posterior approach. RESULTS: Medialisation laryngoplasty combined with arytenoid adduction was performed following unilateral vocal fold paralysis from mediastinal surgery, resulting in severe glottic insufficiency. The patient's voice improved after the initial surgery, but had deteriorated 18 months later. Revision surgery was performed using lateral cricoarytenoid muscle pull surgery, and her voice recovered normally in terms of perceptual impression. The post-operative course was uneventful for 10 months following revision surgery. CONCLUSION: To our knowledge, this is the first case of revision arytenoid adduction performed using a lateral cricoarytenoid muscle pull approach. Lateral cricoarytenoid muscle pull surgery should therefore be considered as a new fenestration approach for arytenoid adduction. PMID- 25120244 TI - Dual-phase (99m)Tc-MIBI scintigraphy with delayed neck and thorax SPECT/CT and bone scintigraphy in patients with primary hyperparathyroidism: correlation with clinical or pathological variables. AB - PURPOSE: The purpose of this study was to assess the relationship between (99m)Tc MIBI and (99m)Tc-MDP bone scintigraphy and clinical or pathological variables, including preoperative serum PTH levels and tumor diameter, in patients with newly diagnosed PHPT. METHODS: Dual-phase (99m)Tc-MIBI planar scintigraphy was performed in 244 patients with PHPT. Of these patients, 155 underwent (99m)Tc-MDP bone scintigraphy to detect bone changes before parathyroidectomy. Factors influencing (99m)Tc-MIBI scintigraphy and (99m)Tc-MDP bone scintigraphy detection rate were assessed using univariate and multivariate logistic regression analysis; optimal cutoff values for predicting positive (99m)Tc-MIBI and (99m)Tc MDP bone scintigraphy were evaluated using ROC analysis. RESULTS: Among 244 patients, 174 (71.31 %) patients with 181 foci had a positive (99m)Tc-MIBI planar scintigraphy; delayed neck and thorax SPECT/CT could identify and locate the (99m)Tc-MIBI lesions but could not find more lesions than planar scintigraphy. 70 (28.69 %) patients had a negative (99m)Tc-MIBI planar scintigraphy. Tumor diameter, serum PTH level and symptoms were statistically significant predictive factors in predicting positive (9m)Tc-MIBI scintigraphy both univariate and multivariate logistic regression analyses. The optimal thresholds for tumor diameter and serum PTH by ROC analysis were 1.03 cm and 127.60 ng/L, respectively. Among 155 patients with bone scintigraphy, (99m)Tc-MDP bone scintigraphy showed positive finding in 80 (51.61 %) patients and negative finding in 75 patients. Univariate logistic regression analysis showed that patient age, sex, tumor diameter and PTH level (>=150 ng/L) were statistically significant in predicting positive (99m)Tc-MDP bone scintigraphy. Multivariate logistic regression analysis showed both tumor diameter and PTH >= 150 ng/L were statistically significant in predicting positive (99m)Tc-MDP bone scintigraphy. The optimal thresholds for tumor diameter and serum PTH by ROC analysis were 1.96 cm and 163.85 ng/L, respectively. CONCLUSIONS: The utility of delayed neck and thorax SPECT/CT over dual-phase (99m)Tc-MIBI planar scintigraphy is that it can identify and locate a parathyroid tumor in about more than 70 % of patients in PHPT and provide the assistance for surgical planning. These studies also suggest that (99m)Tc-MIBI scintigraphy and (99m)Tc-MDP bone scintigraphy are closely correlated with tumor diameter and PTH; which may show negative results when tumor diameter is small and serum PTH level is low. PMID- 25120245 TI - The role of FDG-PET/CT in differentiated thyroid cancer patients with negative iodine-131 whole-body scan and elevated anti-Tg level. AB - AIM: In the follow-up of differentiated thyroid cancer (DTC) after a successful total-near total thyroidectomy and I-131 ablation therapy, anti-thyroglobulin antibodies (anti-Tg) may be persistently or progressively increased in the patients with an undetectable serum thyroglobulin (Tg) level. In these cases, further investigation was performed to search for recurrence/metastases. The aim of our study was clarifying the role of FDG-PET/CT in detecting recurrence/metastasis in patients with DTC with negative serum Tg and elevated anti-Tg level. MATERIALS AND METHODS: A total of 40 patients (32 female, 8 male; mean age: 43.15 years (22-65); mean age at diagnosis: 39.08 (16-64)) with DTC who had undetectable serum Tg and elevated anti-Tg level after a successful initial therapy were included in the study. All of the patients had serum anti-Tg of >40 IU/ml and underwent FDG-PET/CT to search for recurrence/metastasis. RESULTS: Twenty patients (50 %) had recurrence/metastasis on FDG-PET/CT while the other 20 had no pathologic findings. Of the 20 patients who had positive FDG-PET/CT, 12 had a histopathological final diagnosis of which 11 were true positive (TP) and 1 was false positive (FP). On the other hand, 16 of the 40 patients had a histopathological final diagnosis of which 11/16 had TP, 1/16 FP, 3/16 false negative (FN) and 1/16 true negative (TN) findings by PET/CT. The final diagnosis was made by clinical follow-up in the remaining 24 patients. Of these, 8 patients were PET positive, and in 1 (12.5 %) of 8 patients a decrease in serum anti-Tg level, in 2 (25 %) patients a saw-toothed pattern and in 5 (62.5 %) a progressive increase in the serum anti-Tg level were noted during the follow-up. Of the 16 of 24 patients who were diagnosed by clinical follow-up, in 8 a (50 %) decrease in serum anti-Tg level, in 6 (37.5 %) a saw-toothed pattern, and in 2 (12.5 %) a progressively increased anti-Tg level was seen. Of the 40 patients, 14 (35 %) had a diagnosis of recurrence/metastasis finally, with PET/CT detecting 11 (78.6 %) of them. CONCLUSION: The value of a persistently or progressively increased serum anti-Tg level in the follow-up of DTC in the prediction of recurrence/metastasis is controversial. However, it is reported that FDG-PET can be useful in the detection of recurrence/metastasis. We conclude from the available data that PET/CT can be effectively used in the detection of recurrence/metastasis in the follow-up of patients with DTC and negative serum Tg and a persistently/progressively increased anti-Tg level. Besides, one half of the patients were FDG negative, meaning that further studies are needed to assess the prognostic-clinical value of PET negativity. PMID- 25120246 TI - A laparoscopic gastrectomy approach decreases the incidence and severity of emergence agitation after sevoflurane anesthesia. AB - PURPOSE: Compared to open gastrectomy (OG), laparoscopic gastrectomy (LG) has improved short-term outcomes and equivalent oncological outcomes. In this study, a potential short-term advantage of LG over OG, reduced risk of emergence agitation, was evaluated. METHODS: This retrospective study compared LG versus OG with respect to emergence agitation in 400 adult patients who underwent sevoflurane anesthesia. In all cases, a serial Richmond Agitation-Sedation Scale (RASS) assessment was performed in the postanesthesia care unit (PACU). Patients with a RASS score >=+1 at any time were considered to have emergence agitation. Severe agitation was defined as a RASS score of +3 or +4. RESULTS: This study included 214 OG group subjects and 186 LG group subjects in the analysis. The overall incidence of emergence agitation was significantly lower in the LG group than the OG group (23.7 vs. 43.5 %, p < 0.001). The LG group had a significantly lower incidence of severe agitation than the OG group (1.1 vs. 4.7 %, p = 0.035). Multivariate logistic regression analysis demonstrated that the type of surgery (OG vs. LG), as well as current smoking, total dose of rescue opioids used in the PACU, and maximum pain score in the PACU, were independent risk factors for emergence agitation (odds ratio, 1.984; 95 % confidence interval, 1.249-3.153; p = 0.004). Patients with emergence agitation had significantly increased PACU stays (p = 0.024). CONCLUSIONS: Compared to an open approach, a laparoscopic gastrectomy approach can provide the short-term benefit of decreased emergence agitation. PMID- 25120247 TI - Risk factors for weight loss among patients surviving 5 years after esophageal cancer surgery. AB - BACKGROUND: This study aimed to identify factors influencing postoperative weight loss >=15 % in long-term survivors after esophageal cancer surgery. METHODS: A population-based study was conducted in Sweden between 2001 and 2005, with regular follow-up for 5 years. Current weight, weight at operation, and average weight were assessed and dichotomized as weight loss of >=15 %. Logistic regression estimated relative risks of weight loss between pre- and 5 years postoperatively, expressed as odds ratios (ORs) with 95 % confidence intervals (CIs). Statistically significant differences in nutritional symptoms between weight loss groups were analyzed using linear regression models to likewise test as risk factors. Body mass index (BMI) at operation (< or >=25), sex, and preoperative weight loss (< or >=10 %) were tested as risk factors. Nutritional symptoms were selected from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OES18, including fatigue, nausea and vomiting, dyspnoea, appetite loss, diarrhea, and dysphagia, eating difficulties, reflux and pain. RESULTS: A total of 117 patients were included. Patients with preoperative BMI >=25 were at a threefold increased risk (OR 3.2; 95 % CI 1.4-7.3) for postoperative weight loss of >=15 % 5 years after operation. Moreover, eating difficulties, pain, fatigue, nausea and vomiting, and appetite loss were clinically relevant and statistically significantly worse symptoms experienced among those with a weight loss of >=15 % (all at p < 0.05). CONCLUSIONS: Overweight at the time of operation is associated with postoperative weight loss from a long-term perspective. Several nutritional symptoms are associated with weight loss of >15 % 5 years postoperatively. PMID- 25120248 TI - Low infiltration of peritumoral regulatory T cells predicts worse outcome following resection of colorectal liver metastases. AB - BACKGROUND: The tumor-infiltrating lymphocyte (TIL) count in several types of cancer, including colorectal cancer and colorectal liver metastases (CRLM), reportedly predicts survival following resection; however, the prognostic significance of the TIL counts remains controversial. METHODS: In total, 162 patients who underwent potentially curative resection for CRLM from 1992 to 2010 were immunohistochemically analyzed retrospectively. CD4, CD8, and FoxP3 were examined as markers for helper T cells, cytotoxic T cells, and regulatory T cells (Tregs), respectively. The correlation between patients' TIL composition and long term outcome was investigated. RESULTS: The median follow-up time was 46.6 months for all patients and 46.8 months for survivors. Cancer-specific survival (CSS) at 1, 3, and 5 years was 93.2, 65.6, and 51.0 %, respectively. The 5-year disease free survival and CSS among patients with high infiltration of peritumoral Tregs was 44.2 and 74.8 %, respectively, while those of patients with low infiltration of peritumoral Tregs was 18.9 and 40.3 %, respectively (p < 0.01 for both). Multivariate analyses indicated that synchronous liver metastases, hypoalbuminemia, and low peritumoral Treg infiltration were significant predictors of unfavorable CSS. CONCLUSIONS: Low peritumoral Treg infiltration proved to be a significant predictor of unfavorable CSS in patients undergoing resection for CRLM. PMID- 25120249 TI - Impact of distal pancreatectomy on outcomes of peritoneal surface disease treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. AB - BACKGROUND: Left upper quadrant involvement by peritoneal surface disease (PSD) may require distal pancreatectomy (DP) to obtain complete cytoreduction. Herein, we study the impact of DP on outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: Analysis of a prospective database of 1,019 procedures was performed. Malignancy type, performance status, resection status, comorbidities, Clavien-graded morbidity, mortality, and overall survival were reviewed. RESULTS: DP was a component of 63 CRS/HIPEC procedures, of which 63.3 % had an appendiceal primary. While 30-day mortality between patients with and without DP was no different (2.6 vs. 3.2 %; p = 0.790), 30-day major morbidity was worse in patients receiving a DP (30.2 vs. 18.8 %; p = 0.031). Pancreatic leak rate was 20.6 %. Intensive care unit days and length of stay were longer in DP versus non-DP patients (4.6 vs. 3.5 days, p = 0.007; and 22 vs. 14 days, p < 0.001, respectively). Thirty-day readmission was similar for patients with and without DP (29.2 vs. 21.1 %; p = 0.205). Median survival for low-grade appendiceal cancer (LGA) patients requiring DP was 106.9 months versus 84.3 months when DP was not required (p = 0.864). All seven LGA patients undergoing complete cytoreduction inclusive of DP were alive at the conclusion of the study (median follow-up 11.8 years). CONCLUSIONS: CRS/HIPEC including DP is associated with a significant increase in postoperative morbidity but not mortality. Survival was similar for patients with LGA whether or not DP was performed. Thus, the need for a DP should not be considered a contraindication for CRS/HIPEC procedures in LGA patients when complete cytoreduction can be achieved. PMID- 25120250 TI - Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent or progressive diffuse malignant peritoneal mesothelioma: clinicopathologic characteristics and survival outcome. AB - BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive disease for which cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used with remarkable survival benefits. Our aim was to analyze the clinicopathologic characteristics and prognosis of recurrent DMPM managed with iterative CRS and HIPEC. METHODS: A retrospective analysis of a prospectively maintained database for all patients treated for DMPM from 1989 to 2012. RESULTS: Of 205 consecutive CRS and HIPEC procedures, 44 (21.5 %) patients underwent an iterative procedure-22 (50.0 %) males versus 22 (50.0 %) females. Mean age at recurrence was 51.5 years. There was no 30-day mortality following an iterative procedure, and the grade III-V morbidity was 2.3 %. The median overall survival of patients undergoing an iterative CRS and HIPEC was 54 months versus 77 months following an initial CRS and HIPEC (p = 0.96). Patients undergoing an iterative surgery had a 3- and 5-year survival of 61 and 46 %, respectively, versus 60 and 52 % following an initial CRS and HIPEC. Amongst the iterative group, the achieved complete cytoreduction (CC) score was 15.9, 18.2, 22.7, and 43.2 % for CC0, CC1, CC2 and CC3, respectively, versus 3.1, 43.5, 28.6 and 24.8 %, respectively, following initial CRS (p = 0.000). Significant predictors of an improved survival in multivariate analysis were an epithelioid subtype, female sex, complete or near CC (CC0 or CC1), HIPEC regimen utilized, absence of postoperative complication, and age at diagnosis. CONCLUSION: Iterative CRS and HIPEC can be performed safely and appear to have benefits with this group of patients showing an improved median survival. PMID- 25120251 TI - Quality of life after isolated limb infusion for in-transit melanoma of the extremity. AB - BACKGROUND: Isolated limb infusion (ILI) has been associated with persistent edema, numbness, pain, and functional impairment of the treated limb. However, health-related quality of life (HRQOL) has not yet been assessed using a validated questionnaire. METHODS: Functional Assessment of Cancer Therapy Melanoma (FACT-M) questionnaires were collected from subjects enrolled a phase I ILI trial with temozolomide at baseline and 2, 6 weeks, and 3 months post-ILI. Of 28 enrolled patients, 19 patients received maximum tolerated dose of temozolomide and are included in the HRQOL analysis. Clinical and operative variables and treatment response data also were collected. RESULTS: HRQOL scores showed a trend of improvement from baseline through 3-months post-ILI as measured by FACT-M and the melanoma surgery scores. There were no differences in HRQOL when patients were stratified by disease burden, clinical toxicity level, and 3-month disease response. Additionally, fewer patients complained of pain, numbness, and swelling of the affected limb at 3 months post-ILI compared to baseline, and also these symptoms were improved at the immediate postoperative visit compared with baseline. CONCLUSIONS: Despite the known morbidity of ILI, we have demonstrated with a validated HRQOL questionnaire that HRQOL is not adversely impacted at therapeutic doses of temozolomide delivered intra-arterially from baseline through 3 months posttreatment. Patient centered-outcomes should be evaluated as a standard part of all future regional therapy trials using standardized melanoma specific HRQOL questionnaires to more completely evaluate the utility of this type of treatment strategy. PMID- 25120252 TI - Peritoneal surface disease with synchronous hepatic involvement treated with Cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). AB - BACKGROUND: Patients with peritoneal surface disease (PSD) often present with synchronous hepatic involvement (HI). The impact of addressing the hepatic component during CRS/HIPEC on operative and survival outcomes is not clearly defined. METHODS: A prospective database of 1,067 procedures was reviewed based on primary tumor, performance status, resection status, type of liver involvement (superficial or parenchymal) and hepatic resection, morbidity, mortality, and overall survival. RESULTS: There were 108 (10 %) CRS/HIPEC procedures performed with synchronous liver debulking in 99 patients with PSD from 27 (33 %) appendiceal and 32 (39 %) colorectal primary lesions. Ninety percent of patients underwent subsegmental hepatic resection, whereas 22 % had disease with hepatic parenchymal involvement. Median intensive care unit (ICU) and hospital stay were 3.5 and 13.6 days, respectively. Clavien grade III/IV morbidity was similar for patients with or without resected HI (18.9 vs. 22.5 %; p = 0.39). The 30-day mortality rate was 6.5 and 2.8 % (p = 0.07) for patients with and without resected HI, respectively. The median survival for all patients with low-grade appendiceal cancer was 42.1 months with resected HI and 95.5 months without HI (p = 0.03). Median survival for colorectal cancer patients after complete cytoreduction was 21.2 months with HI versus 33.6 months without HI (p = 0.03). CONCLUSIONS: Synchronous resection of limited HI does not increase the morbidity or mortality of CRS/HIPEC procedures. The survival benefit, although still meaningful, was less for patients with HI. Resectable low volume HI in patients with PSD from colon and appendiceal primary lesions should not be considered a contraindication for CRS/HIPEC procedures. PMID- 25120253 TI - Adjuvant imatinib for GIST: the pie is shrinking. PMID- 25120254 TI - The importance of surgical volume on outcomes in thyroid surgery revisited: old is in again : editorial response to "what's old is new again" by Julie Ann Sosa (doi: 10.1245/s10434-014-3850-z). PMID- 25120255 TI - Comparison of long-term outcomes of colonic stent as "bridge to surgery" and emergency surgery for malignant large-bowel obstruction: a meta-analysis. AB - BACKGROUND: The short-term safety and efficacy of insertion of a self-expandable metallic colonic stent followed by elective surgery, bridge to surgery (BTS), for malignant large-bowel obstruction (MLBO) have been well described. However, long term oncological outcomes are still debated. Hence, this study is conducted to evaluate long-term outcomes of colonic stent insertion followed by surgery for MLBO. METHODS: A comprehensive electronic literature search through May 2014 was performed to identify studies comparing long-term outcomes between BTS and emergency surgery for MLBO. The main outcome measures were overall survival (OS), disease-free survival (DFS), and recurrence. A meta-analysis was performed using random-effects models to calculate risk ratios (RRs) with 95 % confidence intervals (95 % CIs). RESULTS: There were 11 studies that matched the criteria for inclusion, yielding a total of 1136 patients, of whom 432 (38.0 %) underwent BTS and 704 (62.0 %) underwent emergency surgery. In OS analyses of all patients and patients who underwent curative resection, BTS was similar to emergency surgery [(RR = 0.95; 95 % CI 0.75-1.21; P = 0.66) (RR = 0.96; 95 % CI 0.67-1.37; P = 0.82), respectively]. DFS (RR = 1.06; 95 % CI 0.91-1.24; P = 0.43) and recurrence (RR = 1.13; 95 % CI 0.82-1.54; P = 0.46) did not differ significantly between the BTS and emergency surgery groups. CONCLUSIONS: Results of this meta analysis on long-term as well as well-described short-term outcomes suggest that BTS could be a promising alternative strategy for MLBO patients. PMID- 25120256 TI - Duration of breastfeeding as a risk factor for vertebral fractures. AB - PURPOSE: Among the risk factors for osteoporosis and fractures, gynecological history (fertile period, parity and breastfeeding) play an important part. Changes in calcium metabolism to enable an adequate mineral transfer to the milk have a prominent role in bone loss during breastfeeding. Data on the influence of breastfeeding in postmenopausal osteoporosis are inconsistent. The aim of the present study was to identify any association between duration of breastfeeding and vertebral fractures in postmenopausal women. METHODS: All patients underwent the following tests: bone mineral density measurements of the lumbar spine (L1 L4) and the total and femoral neck using dual-energy X-ray absorptiometry and antero-posterior and lateral radiography of the thoracic and lumbar spine to identify vertebral fractures. RESULTS: The study involved 752 women with a mean age of 64.5+/-9.3; 23% of them reported vertebral osteoporotic fractures. The women with vertebral fractures had breastfed for longer periods (11.8+/-12.9 vs. 9.3+/-11.2months, p=0.03) and had more pregnancies (2.6+/-2.2 vs. 2.2+/-1.3, p=0.002). Breastfeeding for more than 18months was associated with a two-fold risk of developing vertebral fractures (OR 2.12, 95% CI 1.14-5.38, p=0.04), particularly in those without current or past use of drugs positively affecting bone. CONCLUSIONS: Our study showed an association between long periods of breastfeeding and vertebral fractures, supporting a role for lengthy lactation as a risk factor for osteoporotic fractures after menopause. Bearing in mind all the benefits of breastfeeding, this finding suggests the importance of an adequate calcium and vitamin D intake during pregnancy and breastfeeding, with the aid of dietary supplements if necessary. PMID- 25120257 TI - Heavy metal concentrations of groundwater in the east of Ergene Basin, Turkey. AB - The aim of this research was to investigate the concentrations of the heavy metals (copper, iron, zinc, chromium, cadmium and lead) and determine their relationship between pH and EC in the east of Ergene Basin, Turkey. For this purpose 18 groundwater samples were collected in May 2013. Results show that mean concentrations of Cu, Fe, Zn, Cr, Cd and Pb were, 0.005, 0.012, 0.083, 0.016, 0.000 and 0.0006 mg L(-1) respectively, with the decreasing sequence of Zn > Cr > Fe > Cu > Pb > Cd. No significant correlations were found among metals. Only moderate positive correlation was determined between Pb and pH (r = 0.451; p < 0.05). All metal pollutants studied in the groundwater were below international and national guidelines except Cr. PMID- 25120258 TI - Early life stage (ELS) toxicity of sucralose to fathead minnows, Pimephales promelas. AB - Sucralose, an intense artificial sweetener, has been detected in wastewater and surface waters at concentrations ranging from ng/L to low ug/L. Although over a hundred studies have been conducted to evaluate the safety of sucralose for human consumption, few studies have focused on the chronic ecotoxicological effects of this compound in fish. As a remedy to this data gap, an early-life stage toxicity test was conducted to assess the effects of sucralose on hatching, survival, and growth of fathead minnows (Pimephales promelas). Hatching, survival, and growth were unaffected by 98 mg/L of sucralose. The Lowest-Observed-Effect Concentration (LOEC) and the No-Observed-Effect Concentration (NOEC) for fathead minnows determined by this study are >98 and 98 mg/L, respectively. The results from this study suggest that the concentrations of sucralose detected in the environment are well below those required to cause adverse effects to developing aquatic organisms. PMID- 25120259 TI - Relationship of bifenthrin sediment concentrations to grain size and total organic carbon in California waterbodies: implications for ecological risk. AB - A summary analysis of data sets from six California waterbodies was conducted to determine the relationship of bifenthrin sediment concentrations to: % sand/gravel; % silt; % clay; % silt/clay and % total organic carbon (TOC). The relationship of TOC to % sand/gravel, % silt, % clay, and % silt/clay was also analyzed. Statistically significant and meaningful direct relationships were reported between bifenthrin and % TOC, % silt, % clay and % silt/clay while a significant and meaningful inverse relationship was reported between bifenthrin and % sand/gravel. A significant and meaningful inverse relationship was reported between % TOC and % sand/gravel, while a significant and meaningful direct relationship was reported between % TOC and % silt, % clay and % silt/clay. Significant bifenthrin sediment concentrations would not be expected in non depositional (sand/gravel) areas which have been reported to be dominant in various streams in California's Central Valley and are also the preferred habitat for many benthic macroinvertebrate taxa. PMID- 25120260 TI - Biosensor analysis of anti-citrullinated protein/peptide antibody affinity. AB - Anti-citrullinated protein/peptide antibodies (ACPAs) are detected in rheumatoid arthritis (RA) sera and because of their strict association with the disease are considered marker antibodies, probably endowed with pathogenic potential. Antibody affinity is one of the parameters affecting pathogenicity. Three diagnostic citrullinated peptides-viral citrullinated peptide 1 (VCP1) and VCP2 derived from Epstein-Barr virus (EBV)-encoded proteins and histone citrullinated peptide 1 (HCP1) derived from histone H4-were synthesized as tetrameric multiple antigen peptides and immobilized on sensor chips CM5 type in a Biacore T100 instrument. Specific binding of purified antibodies from RA patients to the three peptides was analyzed by surface plasmon resonance using two arginine-containing sequences as controls. Employing a 1:1 binding model for affinity constant calculation, ACPAs interacted with VCP1 and VCP2 with lower apparent affinity (10(-6) M>KD>10(-7) M) and interacted with HCP1 with higher apparent affinity (KD=10(-8) M). The results indicate that the binding to citrullinated peptides is characterized by wide differences in affinity, with slower association and faster dissociation rates in the case of antibodies to viral citrullinated peptides as compared with antibodies specific for the histone peptide. This biosensor analysis shows the high cross-reactivity of purified ACPAs that bind other citrullinated peptides besides the one used for purification. PMID- 25120263 TI - The interplay of restriction-modification systems with mobile genetic elements and their prokaryotic hosts. AB - The roles of restriction-modification (R-M) systems in providing immunity against horizontal gene transfer (HGT) and in stabilizing mobile genetic elements (MGEs) have been much debated. However, few studies have precisely addressed the distribution of these systems in light of HGT, its mechanisms and its vectors. We analyzed the distribution of R-M systems in 2261 prokaryote genomes and found their frequency to be strongly dependent on the presence of MGEs, CRISPR-Cas systems, integrons and natural transformation. Yet R-M systems are rare in plasmids, in prophages and nearly absent from other phages. Their abundance depends on genome size for small genomes where it relates with HGT but saturates at two occurrences per genome. Chromosomal R-M systems might evolve under cycles of purifying and relaxed selection, where sequence conservation depends on the biochemical activity and complexity of the system and total gene loss is frequent. Surprisingly, analysis of 43 pan-genomes suggests that solitary R-M genes rarely arise from the degradation of R-M systems. Solitary genes are transferred by large MGEs, whereas complete systems are more frequently transferred autonomously or in small MGEs. Our results suggest means of testing the roles for R-M systems and their associations with MGEs. PMID- 25120266 TI - MosaicSolver: a tool for determining recombinants of viral genomes from pileup data. AB - Viral recombination is a key evolutionary mechanism, aiding escape from host immunity, contributing to changes in tropism and possibly assisting transmission across species barriers. The ability to determine whether recombination has occurred and to locate associated specific recombination junctions is thus of major importance in understanding emerging diseases and pathogenesis. This paper describes a method for determining recombinant mosaics (and their proportions) originating from two parent genomes, using high-throughput sequence data. The method involves setting the problem geometrically and the use of appropriately constrained quadratic programming. Recombinants of the honeybee deformed wing virus and the Varroa destructor virus-1 are inferred to illustrate the method from both siRNAs and reads sampling the viral genome population (cDNA library); our results are confirmed experimentally. Matlab software (MosaicSolver) is available. PMID- 25120265 TI - COMET: adaptive context-based modeling for ultrafast HIV-1 subtype identification. AB - Viral sequence classification has wide applications in clinical, epidemiological, structural and functional categorization studies. Most existing approaches rely on an initial alignment step followed by classification based on phylogenetic or statistical algorithms. Here we present an ultrafast alignment-free subtyping tool for human immunodeficiency virus type one (HIV-1) adapted from Prediction by Partial Matching compression. This tool, named COMET, was compared to the widely used phylogeny-based REGA and SCUEAL tools using synthetic and clinical HIV data sets (1,090,698 and 10,625 sequences, respectively). COMET's sensitivity and specificity were comparable to or higher than the two other subtyping tools on both data sets for known subtypes. COMET also excelled in detecting and identifying new recombinant forms, a frequent feature of the HIV epidemic. Runtime comparisons showed that COMET was almost as fast as USEARCH. This study demonstrates the advantages of alignment-free classification of viral sequences, which feature high rates of variation, recombination and insertions/deletions. COMET is free to use via an online interface. PMID- 25120264 TI - Degradation of DNA damage-independently stalled RNA polymerase II is independent of the E3 ligase Elc1. AB - Transcription elongation is a highly dynamic and discontinuous process, which includes frequent pausing of RNA polymerase II (RNAPII). RNAPII complexes that stall persistently on a gene during transcription elongation block transcription and thus have to be removed. It has been proposed that the cellular pathway for removal of these DNA damage-independently stalled RNAPII complexes is similar or identical to the removal of RNAPII complexes stalled due to DNA damage. Here, we show that-consistent with previous data-DNA damage-independent stalling causes polyubiquitylation and proteasome-mediated degradation of Rpb1, the largest subunit of RNAPII, using Saccharomyces cerevisiae as model system. Moreover, recruitment of the proteasome to RNAPII and transcribed genes is increased when transcription elongation is impaired indicating that Rpb1 degradation takes place at the gene. Importantly, in contrast to the DNA damage-dependent pathway Rpb1 degradation of DNA damage-independently stalled RNAPII is independent of the E3 ligase Elc1. In addition, deubiquitylation of RNAPII is also independent of the Elc1-antagonizing deubiquitylase Ubp3. Thus, the pathway for degradation of DNA damage-independently stalled RNAPII is overlapping yet distinct from the previously described pathway for degradation of RNAPII stalled due to DNA damage. Taken together, we provide the first evidence that the cell discriminates between DNA damage-dependently and -independently stalled RNAPII. PMID- 25120268 TI - Rolling circle replication requires single-stranded DNA binding protein to avoid termination and production of double-stranded DNA. AB - In rolling circle replication, a circular template of DNA is replicated as a long single-stranded DNA concatamer that spools off when a strand displacing polymerase traverses the circular template. The current view is that this type of replication can only produce single-stranded DNA, because the only 3'-ends available are the ones being replicated along the circular templates. In contrast to this view, we find that rolling circle replication in vitro generates large amounts of double stranded DNA and that the production of single-stranded DNA terminates after some time. These properties can be suppressed by adding single stranded DNA-binding proteins to the reaction. We conclude that a model in which the polymerase switches templates to the already produced single-stranded DNA, with an exponential distribution of template switching, can explain the observed data. From this, we also provide an estimate value of the switching rate constant. PMID- 25120267 TI - Multiple LacI-mediated loops revealed by Bayesian statistics and tethered particle motion. AB - The bacterial transcription factor LacI loops DNA by binding to two separate locations on the DNA simultaneously. Despite being one of the best-studied model systems for transcriptional regulation, the number and conformations of loop structures accessible to LacI remain unclear, though the importance of multiple coexisting loops has been implicated in interactions between LacI and other cellular regulators of gene expression. To probe this issue, we have developed a new analysis method for tethered particle motion, a versatile and commonly used in vitro single-molecule technique. Our method, vbTPM, performs variational Bayesian inference in hidden Markov models. It learns the number of distinct states (i.e. DNA-protein conformations) directly from tethered particle motion data with better resolution than existing methods, while easily correcting for common experimental artifacts. Studying short (roughly 100 bp) LacI-mediated loops, we provide evidence for three distinct loop structures, more than previously reported in single-molecule studies. Moreover, our results confirm that changes in LacI conformation and DNA-binding topology both contribute to the repertoire of LacI-mediated loops formed in vitro, and provide qualitatively new input for models of looping and transcriptional regulation. We expect vbTPM to be broadly useful for probing complex protein-nucleic acid interactions. PMID- 25120270 TI - Crystal structure of the catalytic core of Rad2: insights into the mechanism of substrate binding. AB - Rad2/XPG belongs to the flap nuclease family and is responsible for a key step of the eukaryotic nucleotide excision DNA repair (NER) pathway. To elucidate the mechanism of DNA binding by Rad2/XPG, we solved crystal structures of the catalytic core of Rad2 in complex with a substrate. Rad2 utilizes three structural modules for recognition of the double-stranded portion of DNA substrate, particularly a Rad2-specific alpha-helix for binding the cleaved strand. The protein does not specifically recognize the single-stranded portion of the nucleic acid. Our data suggest that in contrast to related enzymes (FEN1 and EXO1), the Rad2 active site may be more accessible, which would create an exit route for substrates without a free 5' end. PMID- 25120269 TI - sPARTA: a parallelized pipeline for integrated analysis of plant miRNA and cleaved mRNA data sets, including new miRNA target-identification software. AB - Parallel analysis of RNA ends (PARE) is a technique utilizing high-throughput sequencing to profile uncapped, mRNA cleavage or decay products on a genome-wide basis. Tools currently available to validate miRNA targets using PARE data employ only annotated genes, whereas important targets may be found in unannotated genomic regions. To handle such cases and to scale to the growing availability of PARE data and genomes, we developed a new tool, 'sPARTA' (small RNA-PARE target analyzer) that utilizes a built-in, plant-focused target prediction module (aka 'miRferno'). sPARTA not only exhibits an unprecedented gain in speed but also it shows greater predictive power by validating more targets, compared to a popular alternative. In addition, the novel 'seed-free' mode, optimized to find targets irrespective of complementarity in the seed-region, identifies novel intergenic targets. To fully capitalize on the novelty and strengths of sPARTA, we developed a web resource, 'comPARE', for plant miRNA target analysis; this facilitates the systematic identification and analysis of miRNA-target interactions across multiple species, integrated with visualization tools. This collation of high throughput small RNA and PARE datasets from different genomes further facilitates re-evaluation of existing miRNA annotations, resulting in a 'cleaner' set of microRNAs. PMID- 25120273 TI - Detection of AGEs as markers for carbohydrate metabolism and protein denaturation. AB - Approximately 100 years have passed since the Maillard reaction was first reported in the field of food chemistry as a condensation reaction between reducing sugars and amino acids. This reaction is thought to progress slowly primarily from glucose with proteins in vivo. An early-stage product, called the "Amadori product", is converted into advanced glycation end products. Those accumulate in the body in accordance with age, with such accumulation being enhanced by lifestyle-related diseases that result in the denaturation of proteins. Recent studies have demonstrated that intermediate carbonyls are generated by several pathways, and rapidly generate many glycation products. However, accurate quantification of glycation products in vivo is difficult due to instability and differences in physicochemical properties. In this connection, little is known about the relationship between the structure of glycation products and pathology. Furthermore, the interaction between proteins modified by glycation and receptors for advanced glycation end products is also known to induce the production of several inflammatory cytokines. Therefore, those inhibitors have been developed over the world to prevent lifestyle-related diseases. In this review, we describe the process of protein denaturation induced by glycation and discuss the possibility of using the process as a marker of age related diseases. PMID- 25120272 TI - Syntheses and characterizations of the in vivo replicative bypass and mutagenic properties of the minor-groove O2-alkylthymidine lesions. AB - Endogenous metabolism, environmental exposure, and treatment with some chemotherapeutic agents can all give rise to DNA alkylation, which can occur on the phosphate backbone as well as the ring nitrogen or exocyclic nitrogen and oxygen atoms of nucleobases. Previous studies showed that the minor-groove O(2) alkylated thymidine (O(2)-alkyldT) lesions are poorly repaired and persist in mammalian tissues. In the present study, we synthesized oligodeoxyribonucleotides harboring seven O(2)-alkyldT lesions, with the alkyl group being a Me, Et, nPr, iPr, nBu, iBu or sBu, at a defined site and examined the impact of these lesions on DNA replication in Escherichia coli cells. Our results demonstrated that the replication bypass efficiencies of the O(2)-alkyldT lesions decreased with the chain length of the alkyl group, and these lesions directed promiscuous nucleotide misincorporation in E. coli cells. We also found that deficiency in Pol V, but not Pol II or Pol IV, led to a marked drop in bypass efficiencies for most O(2)-alkyldT lesions. We further showed that both Pol IV and Pol V were essential for the misincorporation of dCMP opposite these minor-groove DNA lesions, whereas only Pol V was indispensable for the T->A transversion introduced by these lesions. Depletion of Pol II, however, did not lead to any detectable alterations in mutation frequencies for any of the O(2)-alkyldT lesions. Thus, our study provided important new knowledge about the cytotoxic and mutagenic properties of the O(2)-alkyldT lesions and revealed the roles of the SOS-induced DNA polymerases in bypassing these lesions in E. coli cells. PMID- 25120274 TI - Brazilian green propolis improves immune function in aged mice. AB - Aging weakened innate and adaptive immunity both quantitatively and qualitatively. Some components in propolis could stimulate immune function in young animals or cultured immune cells in vitro. Few studies had been carried out in the aged. The present study was to evaluate the effects of Brazilian green propolis supplementation on the immunological parameters in aged mice. Eighty Kunming mice, aged 15-18 months, were randomly assigned to the control and three experimental groups supplemented with different doses (83.3, 157.4 and 352.9 mg/kg.bw respectively) of Brazilian green propolis. The experiment lasted for 4 weeks. Contents of total polyphenol, flavonoid, cinnamic acid and artepillin-C in Brazilian green propolis were analyzed. Splenic NK cytotoxic, T lymphocyte proliferation and antibody generation cells, as well as the phagocytosis of peritoneal macrophages, ear swelling, and serum contents of IgG, IgM, hemolysin and cytokines were measured. After 4 weeks of treatment, the phagocytosis of peritoneal macrophages was enhanced in 157.4 mg/kg and 352.9 mg/kg groups. Ear swelling increased in all propolis treatmented groups. Antibodies specific to sheep erythrocytes were higher in the groups receiving 157.4 and 352.9 mg/kg.bw than that of control group. IgG level dramatically increased in the groups receiving 83.3 and 157.4 mg/kg.bw in comparison to the control group. These results indicate that administration of Brazilian green propolis have a positive effect on innate and adaptive immunity in aged mice. PMID- 25120271 TI - The bone-specific Runx2-P1 promoter displays conserved three-dimensional chromatin structure with the syntenic Supt3h promoter. AB - Three-dimensional organization of chromatin is fundamental for transcriptional regulation. Tissue-specific transcriptional programs are orchestrated by transcription factors and epigenetic regulators. The RUNX2 transcription factor is required for differentiation of precursor cells into mature osteoblasts. Although organization and control of the bone-specific Runx2-P1 promoter have been studied extensively, long-range regulation has not been explored. In this study, we investigated higher-order organization of the Runx2-P1 promoter during osteoblast differentiation. Mining the ENCODE database revealed interactions between Runx2-P1 and Supt3h promoters in several non-mesenchymal human cell lines. Supt3h is a ubiquitously expressed gene located within the first intron of Runx2. These two genes show shared synteny across species from humans to sponges. Chromosome conformation capture analysis in the murine pre-osteoblastic MC3T3-E1 cell line revealed increased contact frequency between Runx2-P1 and Supt3h promoters during differentiation. This increase was accompanied by enhanced DNaseI hypersensitivity along with RUNX2 and CTCF binding at the Supt3h promoter. Furthermore, interplasmid-3C and luciferase reporter assays showed that the Supt3h promoter can modulate Runx2-P1 activity via direct association. Taken together, our data demonstrate physical proximity between Runx2-P1 and Supt3h promoters, consistent with their syntenic nature. Importantly, we identify the Supt3h promoter as a potential regulator of the bone-specific Runx2-P1 promoter. PMID- 25120275 TI - Tempol intake improves inflammatory status in aged mice. AB - Oxidative stress is associated with both healthy aging and age-related disease states. In connection with oxidative stress, immunity is also a major component as a result of the chronic, low-grade inflammation associated with the development of tissue aging. Here we show that long-term treatment with the antioxidant tempol extends life-span in mice. Tempol-treated mice exhibited a reduction in mortality at 20 months. Tempol drinking did not have any effect on body weight, amount of visceral adipose tissue, or plasma biochemical parameters in aged mice. Body temperature of aged control mice (which drank only water) was significantly lower than young mice, but this reduction of body temperature was partially restored in aged mice which drank tempol. Plasma thiobarbituric acid reactive substances and C-reactive protein were significantly increased in the control aged mice compared with young mice, but levels of both were normalized by tempol drinking. One of the endogenous antioxidants, ascorbic acid, was significantly increased in the plasma of mice which consumed tempol. The proportion of CD4 lymphocytes in the blood of aged tempol-treated mice was partially increased in comparison to aged control mice. These results suggest that the reduction of mortality by tempol is due to amelioration of chronic inflammation and improved function of the immune system through antioxidant effects. PMID- 25120276 TI - Acetaldehyde is an oxidative stressor for gastric epithelial cells. AB - Alcohol drinking and smoking contain the risk of a carcinogenesis. Acetaldehyde is content in cigarette smoke and an ethanol metabolite. However the clear evidence for reactive oxygen species (ROS) generation by acetaldehyde in gastric cells in vitro is none. In this study, we elucidated acetaldehyde is an oxidative stress inducer on rat gastric epithelial cells by electron paramagnetic resonance measurement in living cells. We also confirmed whether acetaldehyde-induced cellular ROS was derived from mitochondria or not. The results of cellular ROS determination showed that an increment of cellular ROS was shown for 15 min in living cells from exposing 0.1% (v/v) acetaldehyde. Lipid peroxidation in cellular membrane also induced by 0.1% ethanol and the tendency is same in the results of cellular ROS determination. JC-1 stained showed the decrement of mitochondrial membrane potential. These results indicated that acetaldehyde is not merely a necrotizing factor for gastric epithelial cells, but also an oxidative stress inducer via injured mitochondria. PMID- 25120277 TI - Citrulline increases cholesterol efflux from macrophages in vitro and ex vivo via ATP-binding cassette transporters. AB - Reverse cholesterol transport (RCT) is a mechanism critical to the anti atherogenic property of HDL. Although citrulline contributes to the amelioration of atherosclerosis via endothelial nitric oxide production, it remains unclear whether it affects RCT. This study was undertaken to clarify the effects of citrulline on expressions of specific transporters such as ATP binding cassette transporters (ABC)A1 and ABCG1, and the cholesterol efflux from macrophages to apolipoprotein (apo) A-I or HDL in vitro and ex vivo. Citrulline increased ABCA1 and ABCG1 mRNA and protein levels in THP-1 macrophages, translating into enhanced apoA-I- and HDL-mediated cholesterol efflux. In the human crossover study, 8 healthy male volunteers (age 30-49 years) consumed either 3.2 g/day citrulline or placebo for 1 week. Citrulline consumption brought about significant increases in plasma levels of citrulline and arginine. Supporting the in vitro data, monocyte derived macrophages (MDM) differentiated under autologous post-citrulline sera demonstrated enhancement of both apoA-I- and HDL-mediated cholesterol efflux through increased ABCA1 and ABCG1 expressions, compared to MDM differentiated under pre-citrulline sera. However, the placebo did not modulate these parameters. Therefore, in addition to improving endothelium function, citrulline might have an anti-atherogenic property by increasing RCT of HDL. PMID- 25120278 TI - Maternal protein restriction induces alterations in hepatic tumor necrosis factor alpha/CYP7A1 signaling and disorders regulation of cholesterol metabolism in the adult rat offspring. AB - It is well recognized that adverse events in utero impair fetal development and lead to the development of obesity and metabolic syndrome in adulthood. To investigate the mechanisms linking impaired fetal growth to increased cholesterol, an important clinical risk factor characterizing the metabolic syndrome and cardiovascular disease, we examined the impact of maternal undernutrition on tumor necrosis factor-alpha (TNF-alpha)/c-jun N-terminal kinase (JNK) signaling pathway and the cholesterol 7alpha-hydroxylase (CYP7A1) expression in the livers of the offspring with a protein restriction model. The male offspring with intrauterine growth restriction (IUGR) caused by the isocaloric low-protein diet showed decreased liver weight at birth and augmented circulation and hepatic cholesterol levels at 40 weeks of age. Maternal undernutrition significantly upregulated cytokine TNF-alpha expression and JNK phospholytion levels in the livers from fetal age to adulthood. Elevated JNK phospholytion could be linked to downregulated hepatocyte nuclear factor-4alpha and CYP7A1 expression, subsequently led to higher hepatic cholesterol. This work demonstrated that intrauterine malnutrition-induced IUGR might result in intrinsic disorder in hepatic TNF-alpha/CYP7A1 signaling, and contribute to the development of hypercholesterolemia in later life. PMID- 25120279 TI - Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenyl 1-picryl-hydrazyl (DPPH) radical scavenging activity of fasting plasma in healthy subjects. AB - Strawberries contain anthocyanins and ellagitanins which have antioxidant properties. We determined whether the consumption of strawberries increase the plasma antioxidant activity measured as the ability to decompose 2,2-diphenyl-1 picrylhydrazyl radical (DPPH) in healthy subjects. The study involved 10 volunteers (age 41 +/- 6 years, body weight 74.4 +/- 12.7 kg) that consumed 500 g of strawberries daily for 9 days and 7 matched controls. Fasting plasma and spot morning urine samples were collected at baseline, during fruit consumption and after a 6 day wash-out period. DPPH decomposition was measured in both deproteinized native plasma specimens and pretreated with uricase (non-urate plasma). Twelve phenolics were determined with HPLC. Strawberries had no effect on the antioxidant activity of native plasma and circulating phenolics. Non-urate plasma DPPH decomposition increased from 5.7 +/- 0.6% to 6.6 +/- 0.6%, 6.5 +/- 1.0% and 6.3 +/- 1.4% after 3, 6 and 9 days of supplementation, respectively. The wash-out period reversed this activity back to 5.7 +/- 0.8% (p<0.01). Control subjects did not reveal any changes of plasma antioxidant activity. Significant increase in urinary urolithin A and 4-hydroxyhippuric (by 8.7- and 5.9-times after 6 days of supplementation with fruits) was noted. Strawberry consumption can increase the non-urate plasma antioxidant activity which, in turn, may decrease the risk of systemic oxidants overactivity. PMID- 25120280 TI - The inhibitory effect of heat treatment against epithelial-mesenchymal transition (EMT) in human pancreatic adenocarcinoma cell lines. AB - Epithelial-mesenchymal transition (EMT) plays a crucial role in cancer metastasis. In this study, we evaluated the effect of heat treatment on tumor growth factor-beta1 (TGF-beta1)-induced EMT in pancreatic cancer cells and tried to ascertain the mechanism related to any observed effects. Human pancreatic cancer cell lines (BxPC-3, PANC-1 and MIAPaCa-2) were stimulated by TGF-beta1, and evaluated for morphological changes using immunofluorescence and EMT-related factors (i.e., E-cadherin, Vimentin, Snail or ZEB-1) using RT-PCR. To examine the effect of heat on EMT, the cancer cells were heat-treated at 43 degrees C for 1 h then stimulated with TGF-beta1. We then evaluated whether or not heat treatment changed the expression of EMT-related factors and cell migration and also whether Smad activation was inhibited in TGF-beta signaling. After being treated with TGF beta1, pancreatic cancer cells resulted in EMT and cell migration was enhanced. Heat treatment inhibited TGF-beta1-induced changes in morphology, inhibited the expression of EMT-related factors, and attenuated TGF-beta1-induced migration in pancreatic cancer cells. Additionally, we observed that heat treatment blocked TGF-beta1-induced phosphorylation of Smad2 in PANC-1 cells. Our results suggest that heat treatment can suppress TGF-beta1-induced EMT and opens the possibility of a new therapeutic use of hyperthermia as a potential treatment for cancer metastasis. PMID- 25120281 TI - Estimate of dietary phosphorus intake using 24-h urine collection. AB - Increases in serum phosphorus levels and dietary phosphorus intake induces vascular calcification, arterial sclerosis and cardiovascular diseases. Limiting phosphorus intake is advisable, however, no assessment methods are capable of estimating dietary phosphorus intake. We hypothesized that urinary phosphorus excretion can be translated into estimation of dietary phosphorus intake, and we evaluated whether a 24-h urine collection method could estimate dietary phosphorus intake. Thirty two healthy subjects were recruited for this study. Subjects collected urine samples over 24 h and weighed dietary records. We calculated dietary protein intake and phosphorus intake from dietary records and urine collection, and investigated associations between the two methods in estimating protein and phosphorus intake. Significant positive correlations were observed between dietary records and UC for protein and phosphorus intake. The average intakes determined from dietary records were significantly higher than from urine collection for both protein and phosphorus. There was a significant positive correlation between both the phosphorus and protein difference in dietary records and urine collection. The phosphorus-protein ratio in urine collection was significantly higher than in dietary records. Our data indicated that the 24-h urine collection method can estimate the amount of dietary phosphorus intake, and the results were superior to estimation by weighed dietary record. PMID- 25120282 TI - Mitochondrial reactive oxygen species accelerate the expression of heme carrier protein 1 and enhance photodynamic cancer therapy effect. AB - Photodynamic therapy using hematoporphyrin and its derivatives is clinically useful for cancer treatments. It has been reported that cancer cells incorporate hematoporphyrin and its derivatives via heme carrier protein 1, which is a proton coupled folate transporter. However, the mechanism of this protein expression has not been elucidated. In general, the concentration of reactive oxygen species in cancer cells is higher than that in normal cells. We previously reported that reactive oxygen species from mitochondria involved in the expression of peptide transporter 1 and accelerate the uptake of 5-aminolevulinic acid, which is a precursor of protoporphyrin IX. We suggested mitochondrial reactive oxygen species also regulated the expression of heme carrier protein 1. In this study, we used a rat gastric mucosal cell line RGM1 and its cancer-like mutated cell line RGK1. We clarified the expression of heme carrier protein 1 increased in cancer cells and it decreased in manganese superoxide dismutase expressed cancer cells. In addition, the uptake level of hematoporphyrin and photodynamic therapeutic effect were also decreased in manganese superoxide dismutase expressed cancer cells in comparison with cancer cells. Thus, we concluded that mitochondrial reactive oxygen species regulated heme carrier protein 1 expression and photodynamic therapeutic effect. PMID- 25120283 TI - Improvement in medical students' communication and interpersonal skills as evaluated by patient satisfaction questionnaire after curriculum reform. AB - Fifteen years of undergraduate medical education curriculum reform at Saga Medical School was evaluated by measuring medical students' communication and interpersonal skills with a patient satisfaction questionnaire developed by the American Board of Internal Medicine. A multiphase cross-sectional study was conducted at the General Medicine Clinic of Saga Medical School Hospital in phase I (1998-1999), phase II (2001-2002), and phase III (2009-2010). A total of 1,963 patient ratings for 437 medical students' performance was analyzed. The average scores of phases II and III were significantly higher than for phase I. The average score of female students showed a significant difference between phases I and II, but no difference between phases II and III. The average score of male students showed no difference between phases I and II, but significant difference between phases II and III. The phase II curriculum introduced basic clinical skills and examination and improved female students' performance. The phase III curriculum was effective for male students because it emphasized the clinical skill program more and introduced problem-based learning. Curriculum reform at Saga Medical School is considered to have made good progress in improving students' clinical competence and patient-centered attitudes. PMID- 25120284 TI - Diagnostic utility of broad range bacterial 16S rRNA gene PCR with degradation of human and free bacterial DNA in bloodstream infection is more sensitive than an in-house developed PCR without degradation of human and free bacterial DNA. AB - We compared a commercial broad range 16S rRNA gene PCR assay (SepsiTest) to an in house developed assay (IHP). We assessed whether CD64 index, a biomarker of bacterial infection, can be used to exclude patients with a low probability of systemic bacterial infection. From January to March 2010, 23 patients with suspected sepsis were enrolled. CD64 index, procalcitonin, and C-reactive protein were measured on admission. Broad range 16S rRNA gene PCR was performed from whole blood (SepsiTest) or blood plasma (IHP) and compared to blood culture results. Blood samples spiked with Staphylococcus aureus were used to assess sensitivity of the molecular assays in vitro. CD64 index was lower in patients where possible sepsis was excluded than in patients with microbiologically confirmed sepsis (P = 0.004). SepsiTest identified more relevant pathogens than blood cultures (P = 0.008); in three patients (13%) results from blood culture and SepsiTest were congruent, whereas in four cases (17.4%) relevant pathogens were detected by SepsiTest only. In vitro spiking experiments suggested equal sensitivity of SepsiTest and IHP. A diagnostic algorithm using CD64 index as a decision maker to perform SepsiTest shows improved detection of pathogens in patients with suspected blood stream infection and may enable earlier targeted antibiotic therapy. PMID- 25120285 TI - Induction of IL-12 production in human peripheral monocytes by Trypanosoma cruzi Is mediated by glycosylphosphatidylinositol-anchored mucin-like glycoproteins and potentiated by IFN- gamma and CD40-CD40L interactions. AB - Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is characterized by immunopathology driven by IFN-gamma secreting Th1-like T cells. T. cruzi has a thick coat of mucin-like glycoproteins covering its surface, which plays an important role in parasite invasion and host immunomodulation. It has been extensively described that T. cruzi or its products-like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI mucins)-are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-gamma primed murine macrophages. However, little is known about whether T. cruzi or GPI-mucins exert a similar action in human cells. We therefore decided to further investigate the in vitro cytokine production profile from human mononuclear cells from uninfected donors exposed to T. cruzi as well as tGPI-mucins. We observed that both living T. cruzi trypomastigotes and tGPI mucins are potent inducers of IL-12 by human peripheral blood monocytes and this effect depends on CD40-CD40L interaction and IFN-gamma. Our findings suggest that the polarized T1-type cytokine profile seen in T. cruzi infected patients might be a long-term effect of IL-12 production induced by lifelong exposure to T. cruzi tGPI-mucins. PMID- 25120289 TI - Cost of treating diabetic kidney disease. PMID- 25120286 TI - Can the TLR-4-mediated signaling pathway be "a key inflammatory promoter for sporadic TAA"? AB - Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR = 14.4, P = 0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP 9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments. PMID- 25120288 TI - Cholesterol oxidase binds TLR2 and modulates functional responses of human macrophages. AB - Cholesterol oxidase (ChoD) is considered to be an important virulence factor for Mycobacterium tuberculosis (Mtb), but its influence on macrophage activity is unknown. Here we used Nocardia erythropolis ChoD, which is very similar to the Mtb enzyme (70% identity at the amino-acid level), to evaluate the impact of bacterial ChoD on the activity of THP-1-derived macrophages in vitro. We found that ChoD decreased the surface expression of Toll-like receptor type 2 (TLR2) and complement receptor 3 (CR3) on these macrophages. Flow cytometry and confocal microscopy showed that ChoD competed with lipoteichoic acid for ligand binding sites on TLR2 but not on CR3, suggesting that ChoD signaling is mediated via TLR2. Binding of ChoD to the membrane of macrophages had diverse effects on the activity of macrophages, activating p38 mitogen activated kinase and stimulating production of a large amount of interleukin-10. Moreover, ChoD primed macrophages to enhance the production of reactive oxygen species in response to the phorbol myristate acetate, which was reduced by "switching off" TLR-derived signaling through interleukin-1 receptor-associated kinases 1 and 4 inhibition. Our study revealed that ChoD interacts directly with macrophages via TLR2 and influences the biological activity of macrophages during the development of the initial response to infection. PMID- 25120290 TI - Direct costs associated with chronic kidney disease among type 2 diabetic patients in India. AB - The aim of this study was to estimate the direct costs of medical care among hospitalized type 2 diabetic patients with chronic kidney disease (CKD). A total of 209 (M:F, 133:76) patients were divided into groups based on the severity of kidney disease. Group 1 subjects had undergone renal transplantation (n = 12), group 2 was CKD patients on hemodialysis (n = 45), group 3 was patients with CKD, prior to end-stage renal disease (ESRD) (n = 66), and group 4 (n = 86) consisted of subjects without any complications. Details about expenditure per hospitalization, length of stay during admission, direct medical and nonmedical cost, expenditure for the previous two years, and source of bearing the expenditure were recorded in a questionnaire. Diabetic patients with CKD prior to ESRD spend more per hospitalization than patients without any complications. [Median ? 12,664 vs. 3,214]. The total median cost of CKD patients on hemodialysis was significantly higher than other CKD patients (INR 61,170 vs. 12,664). The median cost involved in kidney transplantation was ? 392,920. The total expenditure for hospital admissions in two years was significantly higher for dialysis than transplantation. Patients on hemodialysis or kidney transplantation tend to stay longer as inpatient admissions. The source of funds for the expenditure was mainly personal savings (46%). The expenditure on hospital admissions for CKD was considerably higher, and so, there is a need to develop a protocol on a cost-effective strategy for the treatment of CKD. PMID- 25120287 TI - Lipid isolated from a Leishmania donovani strain reduces Escherichia coli induced sepsis in mice through inhibition of inflammatory responses. AB - Sepsis is the reflection of systemic immune response that manifests in the sequential inflammatory process in presence of infection. This may occur as a result of gram-negative bacterial sepsis including Escherichia coli infection that gives rise to excessive production of inflammatory mediators and causes severe tissue injuries. We have reported earlier that the lipid of attenuated Leishmania donovani suppresses the inflammatory responses in arthritis patients. Using heat killed E. coli stimulated macrophages, we have now investigated the effect of leishmanial total lipid (LTL) isolated from Leishmania donovani (MHO/IN/1978/UR6) for amelioration of the inflammatory mediators and transcriptional factor with suppression of TLR4-CD14 expression. To evaluate the in vivo effect, E. coli induced murine sepsis model was used focusing on the changes in different parameter(s) of lung injury caused by sepsis, namely, edema, vascular permeability, and pathophysiology, and the status of different cytokine chemokine(s) and adhesion molecule(s). Due to the effect of LTL, E. coli induced inflammatory cytokine-chemokine(s) levels were significantly reduced in serum and bronchoalveolar lavage fluid simultaneously. LTL also improved the lung injury and suppressed the cell adhesion molecules in lung tissue. These findings indicate that LTL may prove to be a potential anti-inflammatory agent and provide protection against gram-negative bacterial sepsis with pulmonary impairment. PMID- 25120291 TI - Frequency and clinicopathological correlations of histopathological variants of pediatric idiopathic focal segmental glomerulosclerosis. AB - There is no information on the frequency and clinicopathological correlations of the histopathological variants of primary focal segmental glomerulosclerosis (FSGS) in children presenting with idiopathic nephrotic syndrome (INS) in Pakistan. All consecutive children (<=17 years) who presented with INS, and in whom the histological diagnosis of FSGS was made on renal biopsies, were included in this prospective study. Their clinical, laboratory, and histopathological features at the time of presentation were noted from the case files and the biopsy reports for analysis and clinicopathological correlations. Out of 138 children, 93 (67.4%) were males and 45 (32.6%) were females. The mean age was 8.95 +/- 4.14 (range: 1.5-17) years. All had NS, with steroid dependant NS (SDNS) in 45 (32.6%) and steroid resistant NS (SRNS) in 93 (67.4%) cases. Renal dysfunction at the time of presentation was found in six (4.3%) children. Global glomerulosclerosis was found in 68 (49.3%) cases. The mean number of glomeruli involved by segmental scarring was 2.98 +/- 2.44. FSGS, not otherwise specified (NOS) was the most prevalent variant, comprising 89.1% of all cases. Collapsing variant comprised 8%, tip variant 1.4%, perihilar 0.7%, and cellular 0.7%. Hyaline arteriolosclerosis was found in 13 (9.4%) cases. Mild interstitial fibrosis/tubular atrophy was found in 95 (68.6%) cases, moderate in 18 (13%), and severe in two (1.4%) cases. In conclusion, FSGS, NOS variant was the highly prevalent variant, while collapsing type was also found in small but significant number of cases. Remaining three variants were distinctly rare in our children. PMID- 25120292 TI - Prospective blood pressure measurement in renal transplant recipients. AB - Blood pressure (BP) control at home is difficult when managed only with office blood pressure monitoring (OBPM). In this prospective study, the reliability of BP measurements in renal transplant patients with OBPM and home blood pressure monitoring (HBPM) was compared with ambulatory blood pressure monitoring (ABPM) as the gold standard. Adult patients who had living-related renal transplantation from March 2007 to February 2008 had BP measured by two methods; OBPM and ABPM at pretransplantation, 2(nd), 4(th), 6(th), and 9(th) months and all the three methods: OBPM, ABPM, and HBPM at 6 months after transplantation. A total of 49 patients, age 35 +/- 11 years, on prednisolone, tacrolimus, and mycophenolate were evaluated. A total of 39 were males (79.6%). Systolic BP (SBP) and diastolic BP (DBP) measured by OBPM were higher than HBPM when compared with ABPM. When assessed using OBPM and awake ABPM, both SBP and DBP were significantly overestimated by OBPM with mean difference of 3-12 mm Hg by office SBP and 6-8 mm Hg for office DBP. When HBPM was compared with mean ABPM at 6 months both the SBP and DBP were overestimated by and 7 mm Hg respectively. At 6 months post transplantation, when compared with ABPM, OBPM was more specific than HBPM in diagnosing hypertension (98% specificity, Kappa: 0.88 vs. 89% specificity, Kappa: 0.71). HBPM was superior to OBPM in identifying patients achieving goal BP (89% specificity, Kappa: 0.71 vs. 50% specificity Kappa: 0.54). In the absence of a gold standard for comparison the latent class model analysis still showed that ABPM was the best tool for diagnosing hypertension and monitoring patients reaching targeted control. OBPM remains an important tool for the diagnosis and management of hypertension in renal transplant recipients. HBPM and ABPM could be used to achieve BP control. PMID- 25120293 TI - Renal outcome in biopsy proven cases of graft pyelonephritis. AB - The incidence, risk factors and outcome of graft pyelonephritis are variably described in literature. All patients who had been transplanted at our center between January 2002 and November 2006 and had presented with acute graft dysfunction were subjected to biopsy. Those patients who had neutrophilic casts and interstitial inflammation with predominant neutrophils were included in the study. Out of the 265 patients, 110 were transplanted in the period and underwent biopsy for graft dysfunction. Out of the 110 patients, 26 had biopsy proven acute graft pyelonephritis (AGPN). Nine patients had early AGPN (within 6 months) and the other 17 had late AGPN. Nearly 19% of patients were culture negative and five patients had no clinical features of urinary tract infection; AGPN being a surprise finding on biopsy. Among the risk factors, only hepatitis C virus infection was significantly associated with AGPN. All patients received 4-6 weeks of antibiotics with at least 3 weeks of parenteral antibiotics. Majority (75%) of our patients experienced relapse of AGPN. Graft function was significantly lower 6 months after onset when compared to baseline, portending a poor outcome for these patients. Out of 26, 7 (27%) of our patients had biopsy features of concomitant acute cellular rejection. The treatment of acute rejection, however, did not improve the outcome. PMID- 25120294 TI - Differences among children, adolescents and adults with severe leptospirosis: A comparative analysis. AB - Leptospirosis is a zoonosis of global importance caused by Leptospira interrogans. The aim of this study was to compare the data between children, adolescents and adults with leptospirosis. This is a retrospective study including a total of 373 consecutive patients with leptospirosis, admitted to tertiary hospitals in Northeast of Brazil, from May 1985 to August 2010. The patients were divided into two groups (age <=21 years and >21 years). The adults were 304 (81.5%) of the population, with a mean ge of 41 +/- 13 (range 22-84) years. The pediatric group was 16 +/- 3 (range 9-21) years. Signs and symptoms where similar between the groups, excepting arrhythmia, which was more frequent in adults and vomiting, more common in children (16% vs. 0%, P = 0.04 and 65% vs. 79%, P = 0.02), respectively. Adult group presented with higher serum urea (137 vs. 97 mg/dl, P = 0.002) and creatinine (4.3 vs. 3.0 mg/dl, P = 0.007). Acute kidney injury (AKI) was observed in 80%, mainly in adults (83% vs. 70% P < 0.005). Adults required renal replacement therapy more frequently than children (38% vs. 11%, P < 0.0001). Mortality was higher in adults (14.8% vs. 2.8%, P = 0.005) and in adults with AKI (93% vs. 7%, P < 0.05). There are important differences between the adults and children with leptospirosis. AKI was more frequent in adults and it was associated with increased mortality. PMID- 25120295 TI - Wilson's disease - A rare cause of renal tubular acidosis with metabolic bone disease. AB - We report a 16-year-old boy who presented with weakness of lower limbs. He was diagnosed to have Wilson's disease, renal tubular acidosis and osteoporosis. Screening of siblings showed that his younger sister was also affected by the disease. PMID- 25120296 TI - An interesting case of primary hypoparathyroidism. AB - Primary hypoparathyroidism can occur due to an activating mutation of calcium sensing receptor (CaSR). Most patients remain asymptomatic and therefore not diagnosed until adulthood. We present a 38-year-old lady who had a history of muscle cramps since 8 years. She presented with vomiting, abdomen pain and body ache, showed clinical evidence of hypovolemia, severe hypocalcemia, hypokalemia, hypomagnesemia, hyperphosphatemia and metabolic alkalosis. Her 24 h urinary phosphorus was low and 24 h urinary excretion of sodium, potassium and chloride were high. Her intact parathormone was on the lower side of the normal range. She improved once we had corrected her biochemical abnormalities. By excluding acquired causes of hypoparathyroidism, we are able to conclude that this may be a case of primary hypoparathyroidism due to activating mutation of CaSR. PMID- 25120297 TI - Thyrocervical artery - jugular fistula following internal jugular venous catheterization. AB - Arteriovenous fistula (AVF) is an anomalous communication between an artery and a vein, caused by an iatrogenic or traumatic etiology. Surgically created upper limb AVF remains the preferred vascular access for patients on maintenance hemodialysis. Nonetheless central vein cannulation for hemodialysis is a common procedure done in patients who need hemodialysis. We incidentally detected a thyrocervical artery - jugular fistula in a patient on maintenance hemodialysis. He underwent a successful intra arterial coil embolization of the feeding vessel. Review of literature has shown that, a thyrocervical artery - internal jugular vein arteriovenous fistula following a central venous catheterization has not been reported so far. PMID- 25120298 TI - IgA dominant postinfectious glomerulonephritis: Report of two cases. AB - Immunoglobulin A (IgA) dominant postinfectious glomerulonephritis (IgA PIGN) is a distinct clinical entity increasingly recognized in adult. It usually presents with reduced glomerular filtration rate, heavy proteinuria, and has unfavorable prognosis. Immunofluorescence study of renal biopsy specimens have IgA as dominant or codominant antibody. We encountered two cases of IgA dominant PIGN recently presenting as rapidly progr essive glomerulonephritis and managed conservatively. Both the patients are on follow-up and do not have complete recovery of renal function till date. Long-term follow-up is needed to assess the progression of the disease in these patients. PMID- 25120299 TI - Extending the longevity of a complicated arteriovenous fistula using endovascular intervention. AB - A brachiocephalic arteriovenous fistula was complicated by a central venous stenosis, which could not be relieved. A cephalojugular bypass was performed using an interpositoned graft, which later developed tight stenoses at both ends of the graft. This was successfully treated with endovascular intervention, extending the longevity of the vascular access. PMID- 25120300 TI - Multifocal bacterial osteomyelitis in a renal allograft recipient following urosepsis. AB - Non-tubercular bacterial osteomyelitis is a rare infection. We report on a renal allograft recipient with osteomyelitis complicating urosepsis, manifesting as a multifocal infection poorly responsive to appropriate antibiotics and surgical intervention and culminating in graft loss. PMID- 25120301 TI - Chronic renal failure, hyperkalemia, and colonic ulcers. PMID- 25120303 TI - Apparent steroid resistance associated with prednisolone suspension. PMID- 25120302 TI - D-penicillamine-induced membranous nephropathy. PMID- 25120304 TI - Comment on: Malignant hypertension and nephrotic range proteinuria without hematuria: IgA nephropathy. PMID- 25120305 TI - Acute renal failure secondary to ingestion of unknown mercury containing medicine not due to Ayurvedic medicine. PMID- 25120306 TI - Immunosupression for patients of endocarditis with glomerulonephritis. PMID- 25120307 TI - Seminoma in undescended testes presenting with acute renal failure. PMID- 25120308 TI - Membranous nephropathy and carbamazepine. PMID- 25120309 TI - Unfounded reports on thyroid cancer. PMID- 25120310 TI - Ten tips for authors of scientific articles. AB - Writing a good quality scientific article takes experience and skill. I propose 'Ten Tips' that may help to improve the quality of manuscripts for scholarly journals. It is advisable to draft first version of manuscript and revise it repeatedly for consistency and accuracy of the writing. During the drafting and revising the following tips can be considered: 1) focus on design to have proper content, conclusion, points compliant with scope of the target journal, appropriate authors and contributors list, and relevant references from widely visible sources; 2) format the manuscript in accordance with instructions to authors of the target journal; 3) ensure consistency and logical flow of ideas and scientific facts; 4) provide scientific confidence; 5) make your story interesting for your readers; 6) write up short, simple and attractive sentences; 7) bear in mind that properly composed and reflective titles increase chances of attracting more readers; 8) do not forget that well-structured and readable abstracts improve citability of your publications; 9) when revising adhere to the rule of 'First and Last' - open your text with topic paragraph and close it with resolution paragraph; 10) use connecting words linking sentences within a paragraph by repeating relevant keywords. PMID- 25120311 TI - Role of innate immunity in the pathogenesis of type 1 and type 2 diabetes. AB - The importance of innate immunity in host defense is becoming clear after discovery of innate immune receptors such as Toll-like receptor or Nod-like receptor. Innate immune system plays an important role in diverse pathological situations such as autoimmune diseases. Role of innate immunity in the pathogenesis of metabolic disorders such as type 2 diabetes, metabolic syndrome or atherosclerosis that has not been previously considered as inflammatory disorders, is also being appreciated. Here, the role of innate immunity in the development of type 1 diabetes, a classical organ-specific autoimmune disease, and type 2 diabetes will be discussed, focusing on the role of specific innate immune receptors involved in these disease processes. PMID- 25120312 TI - Withaferin A-caused production of intracellular reactive oxygen species modulates apoptosis via PI3K/Akt and JNKinase in rabbit articular chondrocytes. AB - Withaferin A (WFA) is known as a constituent of Ayurvedic medicinal plant, Withania somnifera, and has been used for thousands of years. Although WFA has been used for the treatment of osteoarthritis (OA) and has a wide range of biochemical and pharmacologic activities, there are no findings suggesting its properties on chondrocytes or cartilage. The aim of the present study is to investigate the effects of WFA on apoptosis with focus on generation of intracellular reactive oxygen species (ROS). Here we showed that WFA significantly increased the generation of intracellular ROS in a dose-dependent manner. We also determined that WFA markedly leads to apoptosis as evidenced by accumulation of p53 by Western blot analysis. N-Acetyl-L-Cystein (NAC), an antioxidant, prevented WFA-caused expression of p53 and inhibited apoptosis of chondrocytes. We also found that WFA causes the activation of PI3K/Akt and JNKinase. Inhibition of PI3K/Akt and JNKinase with LY294002 (LY)/triciribine (TB) or SP600125 (SP) in WFA-treated cells reduced accumulation of p53 and inhibited fragmented DNA. Our findings suggested that apoptosis caused by WFA-induced intracellular ROS generation is regulated through PI3K/Akt and JNKinase in rabbit articular chondrocytes. PMID- 25120313 TI - Clinicopathological features of rare BRAF mutations in Korean thyroid cancer patients. AB - The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame deletion or insertion, and one harbored a two-nucleotide substitution. Of these mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The c.1801A>G mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>G mutation showed extrathyroidal extension or lymph node metastasis. The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features. Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma. [Corrected] PMID- 25120314 TI - Influenza vaccination and associated factors among Korean cancer survivors : a cross-sectional analysis of the Fourth & Fifth Korea National Health and Nutrition Examination Surveys. AB - Influenza vaccination is important for cancer survivors, a population with impaired immunity. This study was designed to assess influenza vaccination patterns among Korean cancer survivors. In this cross-sectional analysis, data were obtained from standardized questionnaires from 943 cancer survivors and 41,233 non-cancer survivors who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Surveys (2007-2011). We identified the adjusted influenza vaccination rates and assessed factors associated with influenza vaccination using multivariate logistic regression. Cancer survivors tended to have a higher adjusted influenza vaccination rate than the general population. The rates for influenza vaccination in specific cancer types such as stomach, hepatic, colon, and lung cancers were significantly higher than non cancer survivors. Among all cancer survivors, those with chronic diseases, elderly subjects, and rural dwellers were more likely to receive influenza vaccination; those with cervical cancer were less likely to receive influenza vaccination. Cancer survivors were more likely to receive influenza vaccinations than non-cancer survivors, but this was not true for particular groups, especially younger cancer survivors. Cancer survivors represent a sharply growing population; therefore, immunization against influenza among cancer survivors should be concerned as their significant preventative healthcare services. PMID- 25120315 TI - Sirolimus conversion efficacy for graft function improvement and histopathology in renal recipients with mild to moderate renal insufficiency. AB - This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement. PMID- 25120316 TI - Four-week effects of allopurinol and febuxostat treatments on blood pressure and serum creatinine level in gouty men. AB - The aim of this study was to observe the effects of uric acid lowering therapy (UALT), febuxostat and allopurinol, on blood pressure (BP) and serum creatinine level. Post-hoc data were derived from a phase-III, randomised, double-blind, 4 week trial of male gouty patients that compared the safety and efficacy of febuxostat and allopurinol in adults with gout. The subjects were randomly assigned to one of five groups, 35-37 in each group (febuxostat: 40, 80, 120 mg/d; allopurinol: 300 mg/d; control group: placebo). Blood pressure and serum creatinine level were measured at baseline and at weeks 2 and 4. Diastolic BP and creatinine level had decreased significantly in the UALT groups compared to the control group at week 4. Diastolic BP had decreased significantly in the allopurinol group and serum creatinine level had decreased significantly in the febuxostat groups at week 4. After adjusting for confounding variables, serum uric acid changes were found to be significantly correlated with changes in serum creatinine level but were not associated with changes in systolic or diastolic BP. UALT in gouty subjects significantly decreased diastolic BP and serum creatinine level. Changes in uric acid were significantly correlated with those in serum creatinine level, suggesting the feasibility of renal function improvement through UALT in gouty men. PMID- 25120317 TI - The risk of osteoporotic fractures according to the FRAX model in Korean patients with rheumatoid arthritis. AB - The aim of the current study is to identify patients without osteoporosis who met the criteria of the fracture risk assessment tool (FRAX) of the National Osteoporosis Foundation (NOF) only. The incidence of fractures was investigated in patients who met only the FRAX criteria of the NOF and patients who presented osteoporosis. Five hundred and forty five patients with rheumatoid arthritis who visited a single center were recruited in Korea. In the follow-up period of median 30 months, the new onset of fractures was investigated. Of 223 patients who have no osteoporosis, 39 (17.4%) satisfied the FRAX criteria for pharmacological intervention. During the follow-up period, 2 new onset fractures occurred in patients who met only the FRAX criteria and 22 new onset fractures did in patients with osteoporosis by bone mineral density. The incidence rate for new onset fractures of patients who met only the FRAX criteria was with 295.93 per 10,000 person-years higher than in the general population with 114.99 per 10,000 person-years. Patients who met the FRAX criteria of the NOF only need pharmacological intervention because their numbers of incidence for new onset fractures are similar to those of patients with osteoporosis by BMD. PMID- 25120318 TI - Follow-up testing of interferon-gamma release assays are useful in ankylosing spondylitis patients receiving anti-tumor necrosis factor alpha for latent tuberculosis infection. AB - We evaluated the utility of follow-up interferon-gamma release assays (IGRAs) for the diagnosis of reactivation of latent tuberculosis infection (LTBI) or new tuberculosis in ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha). The study participants (n=127) had a negative IGRA screening before receiving anti-TNFalpha and were evaluated by follow-up IGRA. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion and anti-TNFalpha, including type and treatment duration. The median duration of anti-TNFalpha was 21.5 months, and the median age was 35.3 yr. Of the 127 patients, IGRA conversion was found in 10 patients (7.9%). There was no significant variation between IGRA conversion rate and any risk factors except for age. IGRA conversion rate was not significantly different between AS and rheumatoid arthritis (P=0.12). IGRA conversion was observed in AS patients receiving anti-TNFalpha in Korea. A follow-up IGRA test can be helpful for identifying LTBI or new tuberculosis in AS patients receiving anti-TNFalpha. PMID- 25120319 TI - Impact of multimodality approach for patients with leptomeningeal metastases from solid tumors. AB - The purpose of this study was to evaluate treatment patterns, outcome and prognosticators for patients with leptomeningeal metastases from solid tumor. Medical records of 80 patients from January 1, 2004 to May 31, 2011 were retrospectively reviewed. Most frequent site of origin was the lung (59%) followed by the breast (25%). Most patients were treated with intrathecal chemotherapy (90%) and/or whole brain radiotherapy (67.5%). Systemic therapy was offered to 27 patients (33.8%). Percentage of patients treated with single, dual, and triple modality were 32.5%, 43.8%, and 23.8%, respectively. Median survival was 2.7 months and 1 yr survival rate was 11.3%. Multivariate analysis showed that negative cerebrospinal fluid cytology, fewer chemotherapy regimen prior to leptomeningeal metastases, whole brain radiotherapy, systemic therapy, and combined modality treatment (median survival; single 1.4 vs. dual 2.8 vs. triple 8.3 months, P<0.001) had statistical significance on survival. Subgroup analysis of non-small cell lung cancer (NSCLC) patients showed that targeted therapy had significant independent impact on survival (median survival; 10.5 vs. 3.0 months, P=0.008). Unlike previous reports, survival of patients with NSCLC primary was comparable to breast primary. Furthermore, combined modality treatment for all patients and additionally targeted therapy for NSCLC patients should be considered in the treatment of leptomeningeal metastases from solid tumor. PMID- 25120320 TI - Acute kidney injury after using contrast during cardiac catheterization in children with heart disease. AB - Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery. PMID- 25120321 TI - Comparison of Korean COPD guideline and GOLD initiative report in term of acute exacerbation: a validation study for Korean COPD guideline. AB - The purpose of this study was to compare the Korean COPD guideline to GOLD consensus report in terms of acute exacerbation. A total of 361 patients were enrolled in this study, and 16.9% of them experienced acute exacerbation during the follow-up. A total of 6.3% of patients in GOLD A, 9.5% in GOLD B, 7.7% in GOLD C and 17.0% of GOLD D experienced exacerbation during the first year of follow-up, respectively (P=0.09). There was no one who experienced exacerbation during the first year of follow-up in the Korean group 'ga'. The 12-month exacerbation rates of Korean group 'na' and 'da' were 4.5% and 16.0%, respectively (P<0.001). We explore the experience of exacerbation in patients with change of their risk group after applying Korean COPD guideline. A total of 16.0% of the patients who were reclassified from GOLD A to Korean group 'da' experienced acute exacerbation,and 15.3% from GOLD B to Korean group 'da' experienced acute exacerbation. In summary, the Korean COPD guideline is useful to differentiate the high risk from low risk for exacerbation in terms of spirometry. This indicates that application of Korean COPD guideline is appropriate to treat Korean COPD patients. PMID- 25120322 TI - Relationship of liver stiffness and controlled attenuation parameter measured by transient elastography with diabetes mellitus in patients with chronic liver disease. AB - High prevalence of diabetes mellitus in patients with liver cirrhosis has been reported in many studies. The aim of our study was to evaluate the relationship of hepatic fibrosis and steatosis assessed by transient elastography with diabetes in patients with chronic liver disease. The study population consisted of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients. The prevalence of diabetes had significant difference among the etiologies of chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3 [18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate analysis showed that the independent predictive risk factors for diabetes were hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR, 1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis but not steatosis assessed by transient elastography has significant relationship with the prevalence of diabetes in patients with chronic liver disease. PMID- 25120323 TI - KISS1 gene polymorphisms in Korean girls with central precocious puberty. AB - Kisspeptin/G-protein couple receptor-54 (GPR54) system plays a key role in the activation of the gonadotropic axis at puberty. Central precocious puberty (CPP) is caused by the premature activation of hypothalamic gonadotropin-releasing hormone secretion. This study was aimed to identify KISS1 gene variations and to investigate the associations between KISS1 gene variations and CPP in Korean girls. All coding exons of KISS1 gene were sequenced in Korean girls with CPP (n = 143) and their healthy controls (n = 101). Nine polymorphisms were identified in KISS1 gene. A novel single-nucleotide polymorphism (SNP), 55648176 T/G, was identified for the first time. SNP 55648184 C/G and 55648186 -/T were detected more frequently in CPP group than in control group. SNP 55648176 T/G was detected less frequently in CPP group than in control group. Haplotype GGGC-ACCC was detected less frequently in CPP group. The genetic variations of KISS1 gene can be contributing factors of development of CPP. The association between the gene variations and CPP should be validated by further evidence obtained from large scaled and functional studies. PMID- 25120324 TI - Early prophylactic versus late selective use of surfactant for respiratory distress syndrome in very preterm infants: a collaborative study of 53 multi center trials in Korea. AB - Pulmonary surfactant (PS) therapy was proven to be highly successful for the treatment of respiratory distress syndrome in premature infants. As a results, early prophylactic (EP) PS therapy has been introduced recently in Europe, the US and Korea. However, no multi-center study was compared EP and late selective (LS) PS therapies in Korea. We performed a retrospective multi-center study to compare the outcomes of EP and LS PS therapies in very preterm infants. We analyzed clinical morbidity and mortality for 1,291 infants in 2010 (LS group) and 1,249 infants in 2011 (EP group); the infants were born <30 weeks of gestation and had birth weight <=1,250 g, and were chosen from 53 neonatal intensive care units in Korea. Compared to the LS group (22.5%), the overall mortality was better in the EP group (19.9%) and there was no increased need for retreatment.There were additional benefits in the EP group such as fewer associated complications. To the best of knowledge, our study is the first nationwide Korean study to compare the outcomes of EP and LS therapies, and it provides evidences that EP PS therapy is important in very preterm infants to improve for survival and reduce morbidities. PMID- 25120325 TI - Effect of renal insufficiency on stone recurrence in patients with urolithiasis. AB - The study was designed to assess the relationship between glomerular filtration rate (GFR) and urinary stone-forming constituents, and to assess the effect of renal insufficiency on stone recurrence risk in first stone formers (SF). Baseline serum creatinine levels were obtained, and renal insufficiency was defined as creatinine clearance <=60 mL/min (Cockroft-Gault). This retrospective case-control study consists of 342 first SF; 171 SF with normal renal function were selected with 1:1 propensity scores matched to 171 SF with renal insufficiency. Urinary metabolic evaluation was compared to renal function. GFR was positively correlated with urinary calcium, uric acid, and citrate excretion. Subjects with renal insufficiency had significantly lower urinary calcium, uric acid, and citrate excretion than those with normal renal function, but not urine volume. With regard to urinary metabolic abnormalities, similar results were obtained. SF with renal insufficiency had lower calcium oxalate supersaturation indexes and stone recurrence rates than SF with normal renal function. Kaplan Meier curves showed similar results. In conclusion, GFR correlates positively with urinary excretion of stone-forming constituents in SF. This finding implies that renal insufficiency is not a risk factor for stone recurrence. PMID- 25120326 TI - Neuropathic pain model of peripheral neuropathies mediated by mutations of glycyl tRNA synthetase. AB - Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. Previous studies have found that, according to CMT patients, neuropathic pain is an occasional symptom of CMT. However, neuropathic pain is not considered to be a significant symptom associated with CMT and, as a result, no studies have investigated the pathophysiology underlying neuropathic pain in this disorder. Thus, the first animal model of neuropathic pain was developed by our laboratory using an adenovirus vector system to study neuropathic pain in CMT. To this end, glycyl-tRNA synthetase (GARS) fusion proteins with a FLAG-tag (wild type [WT], L129P and G240R mutants) were expressed in spinal cord and dorsal root ganglion (DRG) neurons using adenovirus vectors. It is known that GARS mutants induce GARS axonopathies, including CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V). Additionally, the morphological phenotypes of neuropathic pain in this animal model of GARS-induced pain were assessed using several possible markers of pain (Iba1, pERK1/2) or a marker of injured neurons (ATF3). These results suggest that this animal model of CMT using an adenovirus may provide information regarding CMT as well as a useful strategy for the treatment of neuropathic pain. PMID- 25120328 TI - Association between bone mineral density and clinical consequences: cross sectional study of Korean postmenopausal women in an orthopaedic outpatient clinic. AB - This study is to identify the characteristics of BMD and the related clinical consequences through a nationwide, consecutive, cross-sectional study. A total of 1,281 postmenopausal women was enrolled nationwide and underwent measurement for BMD using dual energy x-ray absorptiometry. Following the T-spine and L-spine plane radiography, they were evaluated for vertebral fracture by a semi quantitative method using the Genant's method. Relationship between BMD and osteoporotic fracture and a degree of deformity in vertebral fracture, treatment history in osteoporosis and the EQ-5D was analyzed. The distribution of the normal, osteopenia and osteoporosis group was 25.9%, 37.0%, and 37.2% in lumbar spine, and 31.4%, 45.3%, and 23.3% in femur neck, respectively. BMD in subjects with symptomatic or asymptomatic vertebral fracture was significantly lower than those without fracture. The femur neck and total hip BMDs were significantly lower in hip fracture group (0.646 g/cm(2) and 0.643 g/cm(2), respectively) and wrist fracture group (0.661 g/cm(2) and 0.712 g/cm(2), respectively) than in subjects without fracture (0.721 g/cm(2) and 0.712 g/cm(2), respectively). The BMD was significantly lower with more severe degree of deformity in vertebral fracture and lower scores in mobility, usual activities and pain/discomfort of the EQ-5D. In Korean postmenopausal women, the prevalence of osteoporosis and vertebral, hip and wrist fracture increase and quality of life decreases with lower BMD. PMID- 25120327 TI - The influence of depression, anxiety and somatization on the clinical symptoms and treatment response in patients with symptoms of lower urinary tract symptoms suggestive of benign prostatic hyperplasia. AB - This is the first study to investigate the influence of depression, anxiety and somatization on the treatment response for lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). The LUTS/BPH patients were evaluated with the Korean versions of the International Prostate Symptom Score (IPSS), the Patient Health Questionnaire-9 (PHQ-9), the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the PHQ-15. The primary endpoint was a responder rate defined by the total score of IPSS (<= 7) at the end of treatment. The LUTS/BPH severity was significantly higher in patients with depression (whole symptoms P = 0.024; storage sub-symptom P = 0.021) or somatization (P = 0.024) than in those without, while the quality of life (QOL) was significantly higher in patients with anxiety (P = 0.038) than in those without. Anxious patients showed significantly higher proportion of non-response (odds ratio [OR], 3.294, P = 0.022) than those without, while somatic patients had a trend toward having more non-responders (OR, 2.552, P = 0.067). Our exploratory results suggest that depression, anxiety and somatization may have some influences on the clinical manifestation of LUTS/BPH. Further, anxious patients had a lower response to treatment in patients with LUTS/BPH. Despite of limitations, the present study demonstrates that clinicians may need careful evaluation of psychiatric symptoms for proper management of patients with LUTS/BPH. PMID- 25120330 TI - Transplantation of a horseshoe kidney found during harvest operation of a cadaveric donor: a case report. AB - A 34-yr-old female was diagnosed as being brain dead. Preoperative ultrasound revealed no abnormal focal lesions. However, the horseshoe kidney was identified during organ harvest. En bloc nephrectomy was performed. The kidney was divided at the midline of isthmus. The divided right kidney was discarded due to numerous arteries and veins. The divided left kidney was transplanted. After declamping, the kidney was well perfused and started clearing. Resistive index was 0.72. Glomerular filtration ratio was 84.69 mL/min on postoperative day 14. The horseshoe kidney can be successfully transplanted and could be a good solution for the shortage of organ donors. PMID- 25120329 TI - Aminophylline partially prevents the decrease of body temperature during laparoscopic abdominal surgery. AB - Aminophylline can elicit thermogenesis in rats or increase metabolic rate during cold stress in lambs. We tested the hypothesis that aminophylline would reduce the change in core body temperature during laparoscopic abdominal surgery requiring pneumoperitoneum. Fifty patients were randomly divided into an aminophylline group (n=25) and a saline control group (n=25). Esophageal temperature, index finger temperature, and hemodynamic variables, such as mean blood pressure and heart rate, were measured every 15 min during sevoflurane anesthesia. In the aminophylline group, esophageal temperatures at T45 (36.1+/ 0.38 vs. 35.7+/-0.29, P=0.024), T60 (36.0+/-0.39 vs. 35.6+/-0.28, P=0.053), T75 (35.9+/-0.34 vs. 35.5+/-0.28, P=0.025), T90 (35.8+/-0.35 vs. 35.3+/-0.33, P=0.011), and T105 (35.8+/-0.36 vs. 35.1+/-0.53, P=0.017) and index finger temperatures at T15 (35.8+/-0.46 vs. 34.9+/-0.33, P<0.001), T30 (35.7+/-0.36 vs. 35.0+/-0.58, P=0.029), T45 (35.8+/-0.34 vs. 35.2+/-0.42, P=0.020), T60 (35.7+/ 0.33 vs. 34.9+/-0.47, P=0.010), T75 (35.6+/-0.36 vs. 34.8+/-0.67, P=0.028), T90 (35.4+/-0.55 vs. 34.4+/-0.89, P=0.042), and T105 (34.9+/-0.53 vs. 33.9+/-0.85, P=0.024) were significantly higher than in the saline control group. Aminophylline is effective in maintaining the core temperature through a thermogenic effect, despite reduced peripheral thermoregulatory vasoconstriction. PMID- 25120331 TI - Acute pancreatitis induced by methimazole treatment in a 51-year-old korean man: a case report. AB - Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain. PMID- 25120332 TI - Trends and risk factors of the epidemic of charcoal burning suicide in a recent decade among Korean people. AB - The aims of this study were to analyze annual trends of charcoal burning (CB) suicide, 2000 to 2011, and to examine the risk factors of CB suicide in Korea. Data on suicides (n=138,938) were obtained from the Statistics Korea. The proportion of CB suicides among all suicide deaths reported was 0.7% (84 cases) in 2007, and since 2008 it has rapidly increased to 7.9% (1,251 cases) in 2011. Of significant risk factors of CB suicide, the presence of the media report of Ahn's suicide was the greatest risk factor (adjusted odds ratio, 11.69; 95% CI, 10.30-13.23) of the initial phase of the continuing CB suicides since 2008. Korean Government should urgently consider effective measures against CB suicide, including enforced media regulations on reporting such suicides. PMID- 25120333 TI - Susceptibility of Escherichia coli from community-acquired urinary tract infection to fosfomycin, nitrofurantoin, and temocillin in Korea. AB - With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI. PMID- 25120337 TI - Biometric risk factors for corneal neovascularization associated with hydrogel soft contact lens wear in Korean myopic patients. AB - PURPOSE: To investigate the biometric risk factors for corneal surface complications associated with hydrogel soft contact lens (SCL) fitting in myopic patients in Korea. METHODS: This is a retrospective case-control study. The records of 124 subjects (124 eyes) who wore SCLs on a daily basis were reviewed. Thirty-one patients (31 eyes) who were diagnosed with corneal neovascularization (NV) while wearing SCLs were included in the complication group. Ninety-three age and sex-matched patients (93 eyes) who wore SCLs, who did not have corneal NV and who visited our clinic for correction of refractive errors were included in the control group. The degree of spherical equivalent, astigmatism and corneal base curve radius (BCR) were compared in both groups. RESULTS: Patients with NV exhibited poorer best corrected visual acuity and more myopia than controls (p = 0.008 and 0.006, respectively). In univariate analysis, highly myopic patients ( 9 diopters [D] or higher) were more likely to experience NV (odds ratio [OR], 2.232; 95% confidence interval [CI], 1.602 to 3.105). High astigmatism (>=2 D) increased the risk of complications (OR, 2.717; 95% CI, 1.141 to 6.451). Steep cornea, in which BCR was <7.5 mm, also raised the risk of complications (OR, 4.000; 95% CI, 1.661 to 9.804). Flat cornea was not a risk factor for the development of NV. CONCLUSIONS: High myopia, high astigmatism, and steep cornea seemed to be risk factors in the development of corneal NV in SCL wearers. PMID- 25120336 TI - Higher order aberrations of the corneal surface after laser subepithelial keratomileusis. AB - PURPOSE: To evaluate the changes of higher order aberrations (HOAs) before and after laser subepithelial keratomileusis (LASEK) and to analyze the influence of tear film instability on HOAs of the corneal surface after LASEK. METHODS: In this cross-sectional study, 31 patients who underwent LASEK were divided into dry eye (16 patients, 32 eyes) and non-dry eye groups (15 patients, 30 eyes). Uncorrected distance visual acuity, spherical equivalent refraction, ablation depth, tear film parameters and Ocular Surface Disease Index (OSDI) questionnaire scores were evaluated in both groups. Total HOA root mean square (RMS), third order coma, third-order trefoil and fourth-order spherical aberration (SA) of the corneal surface immediately and at 10 seconds after blinking were measured before and after surgery. RESULTS: The total HOA RMS, coma, trefoil and SA significantly increased after LASEK compared with preoperative values in both groups. In the dry eye group, total HOA RMS, coma and trefoil significantly increased except for SA at 10 seconds after blinking compared with those measured immediately after blinking. In addition, the changes of total HOA RMS, coma and trefoil were negatively correlated with tear film break-up time (R = -0.420, -0.473 and 0.439, respectively), but positively correlated with OSDI score (R = 0.433, 0.499 and 0.532, respectively). In the non-dry eye group, there were no significant differences between HOAs measured at 10 seconds after blinking and those measured immediately after blinking. CONCLUSIONS: The HOAs including coma, trefoil and SA significantly increased after LASEK. The tear film instability in the dry eye can be associated with more deterioration of the optical quality after LASEK, due to more significant increase of total HOA RMS, coma and trefoil. PMID- 25120338 TI - Efficacy of intravitreal anti-vascular endothelial growth factor or steroid injection in diabetic macular edema according to fluid turbidity in optical coherence tomography. AB - PURPOSE: To determine if short term effects of intravitreal anti-vascular endothelial growth factor or steroid injection are correlated with fluid turbidity, as detected by spectral domain optical coherence tomography (SD-OCT) in diabetic macular edema (DME) patients. METHODS: A total of 583 medical records were reviewed and 104 cases were enrolled. Sixty eyes received a single intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity in DME patients was estimated with initial intravitreal SD-OCT and analyzed with color histograms from a Photoshop program. Central macular thickness and visual acuity using a logarithm from the minimum angle of resolution chart, were assessed at the initial period and 2 months after injections. RESULTS: Visual acuity and central macular thickness improved after injections in both groups. In the IVB group, visual acuity and central macular thickness changed less as the intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent less change while central macular thickness had a greater reduction (r = -0.675, p = 0.001) as the intraretinal fluid was more turbid. CONCLUSIONS: IVB and IVTA injections were effective in reducing central macular thickness and improving visual acuity in DME patients. Further, fluid turbidity, which was detected by SD OCT may be one of the indexes that highlight the influence of the steroid dependent pathogenetic mechanism. PMID- 25120339 TI - Intravitreal anti-vascular endothelial growth factor versus observation in acute central serous chorioretinopathy: one-year results. AB - PURPOSE: To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) compared with observation for treating acute central serous chorioretinopathy (CSC). METHODS: A retrospective study of 36 patients with acute CSC, including 21 patients treated with anti-VEGF (anti-VEGF group) and 15 patients with observation (observation group). Patients in the anti-VEGF group received a single dose of bevacizumab or ranibizumab at baseline. Best-corrected visual acuity (BCVA), central foveal thickness (CFT) and resolution of subretinal fluid (SRF) on optical coherence tomography (OCT) were assessed. The integrity of the foveal inner segment/outer segment (IS/OS) line at 12 months was also analyzed. RESULTS: Resolution of SRF was achieved in 20 of 21 eyes in the anti VEGF group and in 12 of 15 eyes in the observation group (p = 0.151). Mean BCVA and CFT were not different between the two groups at 12 months (p > 0.05). The amount of change in BCVA, however, differed significantly between the groups (p = 0.044). Final OCT more frequently detected the foveal IS/OS line in the anti-VEGF group than in the observation group (p = 0.012). CONCLUSIONS: In terms of BCVA, anti-VEGF and observation only had similar therapeutic effects in acute CSC patients. In some patients, however, the rapid resolution of SRF by anti-VEGF might reduce the risk of photoreceptor degeneration and improve long-term visual acuity. PMID- 25120341 TI - Depth and area of retinal nerve fiber layer damage and visual field correlation analysis. AB - PURPOSE: To evaluate the relationship between the structural damage as assessed by time-domain optical coherence tomography (OCT) and functional changes in glaucoma. METHODS: In total, 190 patients with normal tension glaucoma or primary open angle glaucoma were included in this study. The thickness of retinal nerve fiber layer (RNFL) around the optic disc and the area of RNFL defect were determined using OCT scans. The relationships between the RNFL thickness or area of the defect and visual field (VF) indices were assessed using the Lowess function, regression analysis and partial Spearman correlation. The differences between these associations depending on the stage of VF damage were further analyzed. Age, optic disc size, refraction, central corneal thickness and the presence of systemic disease were corrected for in order to exclude confounding factors. RESULTS: A logarithmic scale of RNFL thickness showed a negative linear relationship with VF indices. The area of the RNFL defect showed a weak correlation with the pattern of standard deviation, whereas the remnant RNFL thickness was moderately correlated with the pattern of standard deviation (partial Spearman correlation coefficient, 0.39, -0.47, respectively; p < 0.0001). Many outliers were detected in the Lowess-plotted graphs. Multiplication of the area and the inverted RNFL thickness showed a moderately correlated logarithmic relationship with the VF indices (partial Spearman correlation coefficient, 0.46; 95% confidence interval, 0.34 to 0.57; p < 0.0001). In the severe stage of VF damage, correlation between the area of the RNFL defect and mean deviation was significantly greater than in other stages (partial Spearman correlation coefficient, -0.66; p = 0.02). CONCLUSIONS: The thickness of the RNFL had a negative logarithmic correlation with the VF indices and was more relevant to the VF indices than the area of the RNFL defect, as measured by OCT. PMID- 25120340 TI - Assessment of macular ganglion cell loss patterns in neurologic lesions that mimic glaucoma. AB - PURPOSE: To evaluate patterns of macular retinal ganglion cell (RGC) loss measured by spectral domain optical coherence tomography in patients with neurologic lesions mimicking glaucoma. METHODS: We evaluated four patients with neurological lesions who showed characteristic patterns of RGC loss, as determined by ganglion cell thickness (GCT) mapping. RESULTS: Case 1 was a 30 year-old man who had been treated with glaucoma medication. A left homonymous vertical pattern of RGC loss was observed in his GCT map and a past brain magnetic resonance imaging (MRI) revealed a hemorrhagic lesion around the right optic radiation. Case 2 was a 72-year-old man with a pituitary adenoma who had a binasal vertical pattern of RGC loss that corresponded with bitemporal hemianopsia. Case 3 was a 77-year-old man treated for suspected glaucoma. His GCT map showed a right inferior quadratic pattern of loss, indicating a right superior homonymous quadranopsia in his visual field (VF). His brain MRI revealed a left posterior cerebral artery territory infarct. Case 4 was a 38-year-old woman with an unreliable VF who was referred for suspected glaucoma. Her GCT map revealed a left homonymous vertical pattern of RGC loss, which may have been related to a previous head trauma. CONCLUSIONS: Evaluation of the patterns of macular RGC loss may be helpful in the differential diagnosis of RGC-related diseases, including glaucoma and neurologic lesions. When a patient's VF is unavailable, this method may be an effective tool for diagnosing and monitoring transneuronal retrograde degeneration-related structural changes. PMID- 25120342 TI - Patterns of subsequent progression of localized retinal nerve fiber layer defects on red-free fundus photographs in normal-tension glaucoma. AB - PURPOSE: To investigate patterns of subsequent progression of localized retinal nerve fiber layer (RNFL) defects and to quantify the extent of progression in normal-tension glaucoma (NTG) patients. METHODS: Thirty-three eyes of 33 consecutive NTG patients who had shown continuous progression of localized RNFL defect on serial red-free fundus photographs were selected for the study. Patterns of subsequent progression of localized RNFL defects were categorized, and extents of progression were quantified. Serial evaluations of disc stereophotographs and visual fields were also performed to detect progression. RESULTS: The most common pattern was continuous widening of the defect towards the macula (n = 11, 33.3%) followed by sharpening of the defect border after widening of the defect towards the macula (n = 5, 15.2%), continuous widening of the defect away from the macula (n = 2, 6.1%), and deepening of the defect after appearance of a new defect (n = 2, 6.1%). Four eyes (12.1%) simultaneously showed two patterns of subsequent progression. In 13 eyes that showed continuous widening of the defect, subsequent angular widening towards the macula and away from the macula were 9.2 +/- 6.0 degrees (range, 1.1 degrees to 24.4 degrees ; n = 11) and 5.2 +/- 4.9 degrees (range, 0.3 degrees to 11.3 degrees ; n = 2), respectively. Thirty-two eyes showed no progression of optic disc cupping. Out of the 21 eyes in which Humphrey central 30-2 threshold visual field tests were performed after progression of RNFL defects, 15 eyes showed no deterioration in the visual field. CONCLUSIONS: There were nine patterns of subsequent progression of localized RNFL defects. Among them, continuous RNFL loss proceeding temporally was the most common one. Initial progression of the defect proceeded temporally, especially in the defect located at the inferior fundus, might be at a risk of further RNFL loss temporally. PMID- 25120343 TI - Lateral geniculate body evoked potentials elicited by visual and electrical stimulation. AB - PURPOSE: Blind individuals who have photoreceptor loss are known to perceive phosphenes with electrical stimulation of their remaining retinal ganglion cells. We proposed that implantable lateral geniculate body (LGB) stimulus electrode arrays could be used to generate phosphene vision. We attempted to refine the basic reference of the electrical evoked potentials (EEPs) elicited by microelectrical stimulations of the optic nerve, optic tract and LGB of a domestic pig, and then compared it to visual evoked potentials (VEPs) elicited by short-flash stimuli. METHODS: For visual function measurement, VEPs in response to short-flash stimuli on the left eye of the domestic pig were assessed over the visual cortex at position Oz with the reference electrode at Fz. After anesthesia, linearly configured platinum wire electrodes were inserted into the optic nerve, optic track and LGB. To determine the optimal stimulus current, EEPs were recorded repeatedly with controlling the pulse and power. The threshold of current and charge density to elicit EEPs at 0.3 ms pulse duration was about +/ 10 uA. RESULTS: Our experimental results showed that visual cortex activity can be effectively evoked by stimulation of the optic nerve, optic tract and LGB using penetrating electrodes. The latency of P1 was more shortened as the electrical stimulation was closer to LGB. The EEPs of two-channel in the visual cortex demonstrated a similar pattern with stimulation of different spots of the stimulating electrodes. We found that the LGB-stimulated EEP pattern was very similar to the simultaneously generated VEP on the control side, although implicit time deferred. CONCLUSIONS: EEPs and VEPs derived from visual-system stimulation were compared. The LGB-stimulated EEP wave demonstrated a similar pattern to the VEP waveform except implicit time, indicating prosthetic-based electrical stimulation of the LGB could be utilized for the blind to perceive vision of phosphenes. PMID- 25120344 TI - Comparative quantification of plasma TDRD7 mRNA in cataract patients by real-time polymerase chain reaction. AB - PURPOSE: To investigate the relationship between plasma TDRD7 mRNA and lens transparency, and to evaluate plasma TDRD7 mRNA as a potential marker for cataracts and its sub-type by quantitatively analyzing human peripheral blood. METHODS: Plasma RNA was extracted from 40 patients with cataracts, and 30 normal controls of matched age and gender. Blood cholesterol and fasting glucose were measured, and the RNA extracted from the sample was synthesized into cDNA. After polymerase chain reaction, the results were compared after quantifying the TDRD7 mRNA using ABL1 mRNA for normalization. We analyzed the relative gene expression data via the DeltaDeltaCt method. RESULTS: The normalized 2(-DeltaDeltaCt) of plasma TDRD7 mRNA based on ABL1 mRNA was 1.52 +/- 0.63 in the case of the control group and 1.05 +/- 0.34 in the case of the cataract patients, and the TDRD7 expression level of the cataract patients was lower than that of the control group (p = 0.048). The comparison of the genetic values of different types of cataracts demonstrated that the TDRD7 expression level of the cortical type and mixed type were lower than those of the nuclear type and posterior subcapsular opacity type (p = 0.017). CONCLUSIONS: Human cataracts and the TDRD7 gene loss-of function mutations are strongly causally related, as the expression level of plasma TDRD7 mRNA in patients with cataracts was statistically significantly lower than in the normal control group. PMID- 25120345 TI - Optical coherence tomography to evaluate dengue. PMID- 25120346 TI - Is this really sutureless intrascleral pocket technique of transscleral fixation? PMID- 25120347 TI - A Korean woman with reactive lymphoid hyperplasia of the uvea. PMID- 25120348 TI - Pseudohypopyon after management of posterior capsule rupture using intracameral triamcinolone injection in cataract surgery. PMID- 25120349 TI - Accelerated versus conventional corneal collagen cross-linking in the treatment of mild keratoconus: a comparative study. AB - AIM: To evaluate the use of accelerated corneal collagen cross-linking in the management of mild and moderate progressive keratoconus in comparison with conventional cross-linking. PATIENTS AND METHODS: Prospective randomized interventional case-control clinical trial. A total 25 eyes of 18 patients were randomly divided into two groups: group A included 14 eyes that received accelerated collagen cross-linking; and group B included eleven eyes that received conventional cross-linking (Dresden protocol). Cases with grade 1 and 2 keratoconus (Krumeich classification) with topographic evidence of progression were included. The uncorrected visual acuity and best spectacle-corrected visual acuity were recorded. Pentacam((r)) corneal analysis imaging was used: The maximum and minimum keratometry and the central corneal thickness were recorded. Ocular Response Analyzer((r)) (ORA) measurements were carried out to document the biomechanical parameters. Corneal hysteresis and corneal resistance factor were recorded. Postoperative evaluation included uncorrected visual acuity, best corrected visual acuity, and Pentacam and ORA measurements at 6 and 12 months. The follow-up period was 12 months. RESULTS: A progressive decrease in the flat keratometry, steep keratometry, and mean keratometry was noted throughout the follow-up period in both the accelerated and conventional groups. The improvement in keratometry was not statistically significant. The best spectacle-corrected visual acuity showed a statistically significant improvement in both groups by 1 year. The corneal hysteresis and corneal resistance factor showed nonsignificant improvement in both groups. The central corneal thickness showed a significant thinning at 6 months in both groups but approached baseline values by 12 months. CONCLUSION: Accelerated corneal collagen cross-linking appears to show comparable results to conventional cross-linking in arresting the progression of mild keratoconus. PMID- 25120350 TI - Evaluation of dacryocystorhinostomy using optical coherence tomography and rebamipide ophthalmic suspension. AB - PURPOSE: To evaluate the surgical outcome of dacryocystorhinostomy (DCR) by measuring the tear meniscus, using optical coherence tomography and rebamipide ophthalmic suspension. METHODS: Patients with nasolacrimal obstruction and chronic dacryocystitis who were scheduled for an endonasal DCR underwent tear meniscus examinations before and 2 months after surgery. Vertical scans of the inferior menisci were performed before and at 1, 3, 5, 7, and 10 minutes after the instillation of rebamipide ophthalmic suspension. The tear menisci areas were measured with imaging software. Ten young adults without epiphora formed the control group. RESULTS: Anatomical success was achieved on 22 sides of 21 patients. The patients' postoperative tear menisci were significantly smaller than the preoperative menisci at all points during the test, and the response to volume loading in the postoperative patients was corrected to nearly that of the young, healthy adults. Nevertheless, the postoperative meniscus area tended to be larger than that of the young adults at all points. CONCLUSION: The reduced tear meniscus area after DCR reflected the success of the surgical procedure. However, incomplete recovery of the meniscus after the test might suggest a residual disorder of the lacrimal drainage system after DCR. PMID- 25120352 TI - Neuroretinitis in ocular bartonellosis: a case series. AB - We report a case series of neuroretinitis in ocular bartonellosis and describe the serologic verification for Bartonella henselae. This is a retrospective interventional case series of four patients who presented in the ophthalmology clinic of Hospital Universiti Sains Malaysia from June 2012 to March 2013. All four patients had a history of contact with cats and had fever prior to ocular symptoms. Each patient presented with neuroretinitis characterized by optic disc swelling with macular star. Serology analysis showed strongly positive for B. henselae in all of the patients. All patients were treated with oral azithromycin (except case 4, who was treated with oral doxycycline), and two patients (case 1 and case 3) had poor vision at initial presentation that warranted the use of oral prednisolone. All patients showed a good visual outcome except case 3. Vision-threatening ocular manifestation of cat scratch disease can be improved with systemic antibiotics and steroids. PMID- 25120354 TI - Potential patient benefit of a subcutaneous formulation of tocilizumab for the treatment of rheumatoid arthritis: a critical review. AB - Treatment of rheumatoid arthritis (RA) was revolutionized during the last decade with the development of new biologic disease-modifying anti-rheumatic drugs (DMARDs) enabling the targeting of immune cells and cytokines other than tumor necrosis factor (TNF). Subcutaneous formulations of the newer biologic DMARDs facilitate not only patients' emancipation from the hospital, but reduce both societal and medical costs. Intravenous tocilizumab (TCZ) in RA has an efficacy and safety profile similar to anti-TNF in both the short and long-term. However, TCZ can be administered in monotherapy without loss of efficacy when patients do not tolerate methotrexate or synthetic DMARDs. TCZ is consistently found superior to methotrexate and possibly superior to adalimumab in monotherapy in randomized controlled trials. Subcutaneous administration of TCZ is as effective and safe as its intravenous administration in RA patients during the first year of treatment. Similar to intravenous TCZ, patients' weight and possibly previous use of anti TNF influence the efficacy of subcutaneous TCZ. Additionally, combination with synthetic DMARDs seems to expose RA patients to more adverse events independently of its administration route. Pharmacokinetics of different administration routes could potentially lead to differences in efficacy, adverse events, and auto immunogenicity. The concentration of free TCZ before new TCZ dose (C trough) is higher in the subcutaneous route, while the maximal concentration of free TCZ is higher in the intravenous route. The subcutaneous dosages of TCZ 162 mg every week, and every 2 weeks in RA patients with low body weight (<60 kg) work well. Nevertheless, dosage and intervals of subcutaneous TCZ administration could be adjusted during the course of treatment since 80% of non-Japanese RA patients with usually higher body weight achieved similar efficacy with the low TCZ dosage in combination with a synthetic DMARD. Patients want effective, easy-to administer therapy with sustained prolonged efficacy without the need of polypharmacy and with minimal to no side effects. Subcutaneous TCZ in RA patients in monotherapy seems to live up to patients' expectations. PMID- 25120353 TI - Design, synthesis, and anticancer activity of novel berberine derivatives prepared via CuAAC "click" chemistry as potential anticancer agents. AB - A series of novel derivatives of phenyl-substituted berberine triazolyls has been designed and synthesized via copper-catalyzed azide-alkyne cycloaddition click chemistry in an attempt to develop antitumor agents. All of the compounds were evaluated for anticancer activity against a panel of three human cancer cell lines, including MCF-7 (breast), SW-1990 (pancreatic), and SMMC-7721 (liver) and the noncancerous human umbilical vein endothelial cell (HUVEC) cell lines. The results indicated that most of the compounds displayed notable anticancer activities against the MCF-7 cells compared with berberine. Among these derivatives, compound 16 showed the most potent inhibitory activity against the SW-1990 and SMMC-7721 cell lines, with half-maximal inhibitory concentration (IC50) values of 8.54+/-1.97 MUM and 11.87+/-1.83 MUM, respectively. Compound 36 exhibited the most potent inhibitory activity against the MCF-7 cell line, with an IC50 value of 12.57+/-1.96 MUM. Compound 16 and compound 36 exhibited low cytotoxicity in the HUVEC cell line, with IC50 values of 25.49+/-3.24 MUM and 30.47+/-3.47 MUM. Furthermore, compounds 14, 15, 16, 17, 18, 32, and 36 exhibited much better selectivity than berberine toward the normal cell line HUVEC. PMID- 25120351 TI - Managing Sjogren's Syndrome and non-Sjogren Syndrome dry eye with anti inflammatory therapy. AB - Dry eye from Sjogren's syndrome is a multifactorial disease that results in dysfunction of the lacrimal functional unit. Studies have shown changes in tear composition, including inflammatory cytokines, chemokines, and metalloproteinase. T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands in patient and animal models. This inflammation is in part responsible for the pathogenesis of the disease, which results in symptoms of eye irritation, ocular surface epithelial disease, and loss of corneal barrier function. There are a number of anti-inflammatory approaches for treating this disease. The current study reviews details of immune response and anti-inflammatory therapies used to control this disease. PMID- 25120355 TI - Effects of annatto-derived tocotrienol supplementation on osteoporosis induced by testosterone deficiency in rats. AB - BACKGROUND: Previous animal models have demonstrated that tocotrienol is a potential treatment for postmenopausal osteoporosis. This study evaluated the antiosteoporotic effects of annatto-derived tocotrienol (AnTT) using a testosterone-deficient osteoporotic rat model. METHODS: Forty rats were divided randomly into baseline, sham, orchidectomized, AnTT, and testosterone groups. The baseline group was euthanized without undergoing any surgical treatment or intervention. The remaining groups underwent orchidectomy, with the exception of the sham group. AnTT 60 mg/kg/day was given orally to the AnTT group, while the testosterone group received testosterone enanthate 7 mg/kg per week intramuscularly for 8 weeks. Structural changes in trabecular bone at the proximal tibia were examined using microcomputed tomography. Structural and dynamic changes at the distal femur were examined using histomorphometric methods. Serum osteocalcin and C-terminal of type 1 collagen crosslinks were measured. Bone-related gene expression in the distal femur was examined. RESULTS: There were significant degenerative changes in structural indices in the orchidectomized group (P<0.05), but no significant changes in dynamic indices, bone remodeling markers, or gene expression (P>0.05) when compared with the sham group. The AnTT group showed significant improvement in structural indices at the femur (P<0.05) and significantly increased expression of bone formation genes (P<0.05). Testosterone was more effective than AnTT in preventing degeneration of bone structural indices in the femur and tibia (P<0.05). CONCLUSION: AnTT supplementation improves bone health in testosterone-deficient rats by enhancing bone formation. Its potential should be evaluated further by varying the dosage and treatment duration. PMID- 25120356 TI - The effects of Tai Ji Quan training on limits of stability in older adults. AB - BACKGROUND: Limits of stability, defined as the ability to maintain the center of gravity within the boundary of the base of support, is critically important for older adults in performing their activities of daily living. However, few exercise programs specifically tailored to enhance limits of stability exist. The primary purpose of this study was to determine whether a therapeutically designed intervention, Tai Ji Quan: Moving for Better Balance (TJQMBB), could improve limits of stability in older adults. A secondary purpose was to examine concomitant change in limits of stability and physical performance as a result of the intervention. METHODS: A single-group design was used in which 145 community dwelling older adults (average age: 75 years) were enrolled in TJQMBB classes, participating twice weekly for 48 weeks. Primary outcome measures were three indicators of limits of stability (LOS) (endpoint excursion, movement velocity, and directional control), with secondary measures of physical performance being Timed Up and Go and 50-foot speed walk (in seconds), which were assessed at baseline, 24 weeks, and 48 weeks. Changes in the repeated measures of outcome variables were analyzed via latent curve analysis. RESULTS: At 48 weeks, a significant rate of change (improvement) over time was observed in the three limits of stability indicators (endpoint execution: 8.30% LOS, P<0.001; movement velocity: 0.86 degrees/second, P<0.001; directional control: 6.79% of 100, P<0.001); all reached a threshold of real change as judged by the minimal detectable change values. Improvements in the three limits of stability measures were concomitantly correlated with improved (reduced times) performance scores in the Timed Up and Go (-0.30, -0.45, and -0.55, respectively) and 50-foot walk ( 0.33, -0.49, and -0.41, respectively). CONCLUSION: In this single-group study, community-dwelling older adults trained through TJQMBB significantly improved their limits of stability, providing preliminary support for the use of TJQMBB as a therapeutic modality for enhancing functional activities in older adults. PMID- 25120357 TI - Increased body fat rather than body weight has harmful effects on 4-year changes of renal function in the general elderly population with a normal or mildly impaired renal function. AB - BACKGROUND: With increasing age, body fat increases and muscle mass reduces. Even people with a normal weight may have a higher percentage of body fat. The aim of this study is to investigate the association between increased body fat and renal function decline (RFD) in the general elderly population with normal or mildly impaired renal function. METHOD: We conducted a prospective study of 615 healthy individuals in the general Korean population aged >= 60 years who participated in two health screening check-ups separated by a 4-year period. Obesity was defined as the highest sex-specific tertiles of the percentage body fat (PBF). The main outcome was changes of estimated glomerular filtration rate (eGFR) during the 4 years. Significant RFD was defined as a decrease of eGFR over the upper quartile (<=-2.1% per year). RESULTS: The mean age was 67.2 +/- 6.6 years. The median value of the absolute decline in the eGFR and the percent change was -3.0 mL/minute/1.73 m(2) and -0.87%/year in men and -3.1 mL/minute/1.73 m(2) and 0.89%/year in women, respectively. When stratified by sex-specific PBF tertiles, pronounced differences were observed in both sexes; those at the highest tertile of PBF showed the greatest decline in eGFR. Even after adjustments for traditional risk factors of RFD, PBF was independently associated with eGFR changes (beta=-0.181; P<0.001). In addition, the harmful effect of a high PBF was consistently found in subjects with a normal weight, too (beta=-0.141; P=0.006). Cases of significant RFD occurred in 181 participants (29.4%), and the risk was higher in obese participants as compared with the nonobese participants. The odd ratios (95% confidence interval) for significant RFD were 2.76 (1.28-7.74) in men and 2.02 (1.06-4.43) in women in a whole population and 3.15 (1.03-18.52) in men and 1.44 (1.01-3.28) in women with a normal weight, respectively. CONCLUSION: Among the elderly population without comorbidities, increased body fat has a harmful effect on RFD, irrespective of body weight. PMID- 25120358 TI - Age as a risk factor for acute mountain sickness upon rapid ascent to 3,700 m among young adult Chinese men. AB - BACKGROUND: The aim of this study was to explore the relationship between age and acute mountain sickness (AMS) when subjects are exposed suddenly to high altitude. METHODS: A total of 856 young adult men were recruited. Before and after acute altitude exposure, the Athens Insomnia Scale score (AISS) was used to evaluate the subjective sleep quality of subjects. AMS was assessed using the Lake Louise scoring system. Heart rate (HR) and arterial oxygen saturation (SaO2) were measured. RESULTS: Results showed that, at 500 m, AISS and insomnia prevalence were higher in older individuals. After acute exposure to altitude, the HR, AISS, and insomnia prevalence increased sharply, and the increase in older individuals was more marked. The opposite trend was observed for SaO2. At 3,700 m, the prevalence of AMS increased with age, as did severe AMS, and AMS symptoms (except gastrointestinal symptoms). Multivariate logistic regression analysis showed that age was a risk factor for AMS (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.13, P<0.05), as well as AISS (adjusted OR 1.39, 95% CI 1.28-1.51, P<0.001). CONCLUSION: The present study is the first to demonstrate that older age is an independent risk factor for AMS upon rapid ascent to high altitude among young adult Chinese men, and pre-existing poor subjective sleep quality may be a contributor to increased AMS prevalence in older subjects. PMID- 25120359 TI - The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient. AB - The applications of ethylenediaminetetraacetic acid (EDTA) have been expanded from the treatment of heavy metal poisoning to chelation therapies for atherosclerosis, heart disease, and cancers, in which EDTA reduces morbidity and mortality by chelating toxic metal ions. In this study, EDTA was used in a drug delivery system by adopting an NH4EDTA gradient method to load doxorubicin into liposomes with the goal of increasing therapeutic effects and decreasing drug related cytotoxicity. The particle size of the optimum NH4EDTA gradient liposomes was 79.4+/-1.87 nm, and the entrapment efficiency was 95.54%+/-0.59%. In vitro studies revealed that liposomes prepared using an NH4EDTA gradient possessed long term stability and delayed drug release. The in vivo studies also showed the superiority of the new doxorubicin formulation. Compared with an equivalent drug dose (5 mg/kg) prepared by (NH4)2SO4 gradient, NH4EDTA gradient liposomes showed no significant differences in tumor inhibition ratio, but cardiotoxicity and liposome-related immune organ damage were lower, and no drug-related deaths were observed. These results show that use of the NH4EDTA gradient method to load doxorubicin into liposomes could significantly reduce drug toxicity without influencing antitumor activity. PMID- 25120360 TI - Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes. AB - Baicalin (BA) is a major constituent of Scutellaria baicalensis Georgi, a medicinal herb. Previous pharmacokinetic studies of BA showed its low oral bioavailability. The aim of the present study was to develop a novel BA-loaded liposome (BA-LP) to enhance oral bioavailability. BA-LP, composed of BA, Tween((r)) 80, Phospholipon((r)) 90H, and citric acid at weight ratio of 96/50/96/50, respectively, was prepared by the effervescent dispersion technique and characterized in terms of morphology, size, zeta potential, encapsulation efficiency, and the in vitro release. Pharmacokinetics and biodistribution studies were carried out in rats after oral administration of BA-LP and a carboxymethyl cellulose suspension containing BA (BA-CMC) as a control. BA-LP exhibited a spherical shape by transmission electron microscopy observation. BA LP had a mean particle size of 373+/-15.5 nm, zeta potential of -20.1+/-0.22 mV, and encapsulation efficiency of 82.7%+/-0.59%. The BA-LP showed a sustained release behavior, and the in vitro drug-release kinetic model fit well with the Weibull distribution equation: lnln (1/(1-Q)) =0.609 lnt -1.230 (r=0.995). The oral bioavailability and the peak concentration of the BA-LP was threefold and 2.82-fold that of BA-CMC, respectively. The in vivo distribution results indicated that drug concentrations were significantly increased in the liver, kidney, and lung in the case of BA-LP, which were 5.59-fold, 2.33-fold, and 1.25 fold higher than those of BA-CMC, respectively. In conclusion, the study suggested that BA-LP might be a potential oral drug delivery system to improve bioavailability of BA. PMID- 25120361 TI - Effects of size and surface of zinc oxide and aluminum-doped zinc oxide nanoparticles on cell viability inferred by proteomic analyses. AB - Although the health effects of zinc oxide nanoparticles (ZnONPs) on the respiratory system have been reported, the fate, potential toxicity, and mechanisms in biological cells of these particles, as related to particle size and surface characteristics, have not been well elucidated. To determine the physicochemical properties of ZnONPs that govern cytotoxicity, we investigated the effects of size, electronic properties, zinc concentration, and pH on cell viability using human alveolar-basal epithelial A549 cells as a model. We observed that a 2-hour or longer exposure to ZnONPs induced changes in cell viability. The alteration in cell viability was associated with the zeta potentials and pH values of the ZnONPs. Proteomic profiling of A549 exposed to ZnONPs for 2 and 4 hours was used to determine the biological mechanisms of ZnONP toxicity. p53-pathway activation was the core mechanism regulating cell viability in response to particle size. Activation of the Wnt and TGFbeta signaling pathways was also important in the cellular response to ZnONPs of different sizes. The cadherin and Wnt signaling pathways were important cellular mechanisms triggered by surface differences. These results suggested that the size and surface characteristics of ZnONPs might play an important role in their observed cytotoxicity. This approach facilitates the design of more comprehensive systems for the evaluation of nanoparticles. PMID- 25120362 TI - Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions. AB - There has been an increasing interest in the study of the innate immune system in recent years. However, few studies have focused on whether innate immunity can acquire tolerance. Therefore, in this study, we investigated tolerance in the innate immune system via the consecutive weekly and daily injections of emulsions modified with polyethylene glycol (PEG), referred to as PEGylated emulsions (PE). The effects of these injections of PE on pharmacokinetics and biodistribution were studied in normal and macrophage-depleted rats. Additionally, we evaluated the antigenic specificity of immunologic tolerance. Immunologic tolerance against PE developed after 21 days of consecutive daily injections or the fourth week of PE administration. Compared with a single administration, it was observed that the tolerant rats had a lower rate of PE clearance from the blood, which was independent of the stress response. In addition, weekly PE injections caused injury to the spleen. Furthermore, the rats tolerant to PEs with the methoxy group (-OCH3) of PEG, failed to respond to the PEs with a different terminal group of PEG or to non-PEG emulsions. Innate immunity tolerance was induced by PE, regardless of the mode of administration. Further study of this mechanism suggested that monocytes play an essential role in the suppression of innate immunity. These findings provide novel insights into the understanding of the innate immune system. PMID- 25120363 TI - Development and characterization of magnetic iron oxide nanoparticles with a cisplatin-bearing polymer coating for targeted drug delivery. AB - A highly selective and efficient cancer therapy can be achieved using magnetically directed superparamagnetic iron oxide nanoparticles (SPIONs) bearing a sufficient amount of the therapeutic agent. In this project, SPIONs with a dextran and cisplatin-bearing hyaluronic acid coating were successfully synthesized as a novel cisplatin drug delivery system. Transmission electron microscopy images as well as X-ray diffraction analysis showed that the individual magnetite particles were around 4.5 nm in size and monocrystalline. The small crystallite sizes led to the superparamagnetic behavior of the particles, which was exemplified in their magnetization curves, acquired using superconducting quantum interference device measurements. Hyaluronic acid was bound to the initially dextran-coated SPIONs by esterification. The resulting amide bond linkage was verified using Fourier transform infrared spectroscopy. The additional polymer layer increased the vehicle size from 22 nm to 56 nm, with a hyaluronic acid to dextran to magnetite weight ratio of 51:29:20. A maximum payload of 330 MUg cisplatin/mL nanoparticle suspension was achieved, thus the particle size was further increased to around 77 nm with a zeta potential of -45 mV. No signs of particle precipitation were observed over a period of at least 8 weeks. Analysis of drug-release kinetics using the dialysis tube method revealed that these were driven by inverse ligand substitution and diffusion through the polymer shell as well as enzymatic degradation of hyaluronic acid. The biological activity of the particles was investigated in a nonadherent Jurkat cell line using flow cytometry. Further, cell viability and proliferation was examined in an adherent PC-3 cell line using xCELLigence analysis. Both tests demonstrated that particles without cisplatin were biocompatible with these cells, whereas particles with the drug induced apoptosis in a dose-dependent manner, with secondary necrosis after prolonged incubation. In conclusion, combination of dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising approach for magnetic drug targeting in the treatment of cancer. PMID- 25120364 TI - Examining the relationship between adherence and satisfaction with antidepressant treatment. AB - BACKGROUND: Adherence to antidepressant treatment is an essential step in the management of patients with major depressive disorder, and several factors can contribute to antidepressant nonadherence. Evidence supports the hypothesis that patient treatment satisfaction will result in improved adherence; therefore, the aim of this study was to investigate the relationship between patient treatment satisfaction and adherence to antidepressants, and the role of patient beliefs toward medication in patient treatment satisfaction. METHODS: This was an observational, nonexperimental survey of all patients attending Al Amal Psychiatric Hospital (500 beds) in Riyadh, Saudi Arabia. Medication adherence was assessed using the eight-item Morisky Medication Adherence Scale (MMAS-8), and treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4). RESULTS: A total of 403 patients met the inclusion criteria; 50.4% were females; participant age ranged from 18 to 60 years; and 16 % of the patients reported side effects after using antidepressants. Both males and females reported high treatment satisfaction rates: - 79.21% (standard deviation [SD] 8.52) and 86.55% (SD 14.34), respectively - with statistically significant associations found for female sex, older age, and three or more physician visits per year. Adherence to antidepressants was associated with treatment satisfaction with the antidepressants, with a direct positive correlation. CONCLUSION: The results of this study showed high treatment satisfaction scores among patients in Saudi Arabia with major depressive disorder, which correlated with adherence and patient beliefs about the necessity of treatment. This finding has improved the understanding of the role of patient beliefs, which can help caregivers and other stakeholders to improve satisfaction with antidepressants. PMID- 25120365 TI - A systematic review of randomized controlled trials of bupropion versus methylphenidate in the treatment of attention-deficit/hyperactivity disorder. AB - BACKGROUND: Some trials have suggested that bupropion, as well as methylphenidate, is beneficial in the treatment of attention deficit/hyperactivity disorder (ADHD). OBJECTIVES: The purpose of this systematic review was to summarize the efficacy, acceptability, and tolerability of bupropion in comparison with methylphenidate for ADHD treatment. Included studies were randomized controlled trials (RCTs) that compared bupropion and methylphenidate. Clinical studies conducted between January 1991 and January 2014 were reviewed. DATA SOURCES: MEDLINE((r)), EMBASETM, CINAHL, PsycINFO((r)), and the Cochrane Controlled Trials Register were searched in January 2014. Additionally, clinical trials were identified from the databases of ClinicalTrials.gov and the EU Clinical Trials Register. STUDY ELIGIBLE CRITERIA PARTICIPANTS AND INTERVENTIONS: All RCTs of bupropion and methylphenidate reporting final outcomes relevant to 1) ADHD severity, 2) response or remission rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse events. Language restriction was not applied. STUDY APPRAISAL AND SYNTHESIS METHODS: The relevant clinical trials were examined and the data of interest were extracted. Additionally, the risks of bias were also inspected. The efficacy outcomes were the mean changed scores of ADHD rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate and the discontinuation rate due to adverse events were determined. Relative risks and weighted mean differences or standardized mean differences with 95% confidence intervals were estimated using a random effect model. RESULTS: A total of 146 subjects in four RCTs comparing bupropion with methylphenidate in the treatment of ADHD were included. The pooled mean changed scores of the Iowa-Conner's Abbreviated Parent and Teacher Questionnaires and the ADHD Rating Scale-IV for parents and teachers of children and adolescents with ADHD in the bupropion- and methylphenidate-treated groups were not significantly different. Additionally, the pooled mean changed score in adult ADHD between the two groups, measured by the ADHD Rating Scale-IV and the Adult ADHD Rating Scale, was also not significantly different. The pooled rates of response, overall discontinuation, and discontinuation due to adverse events between the two groups were not significantly different. CONCLUSION: Based on limited data from this systematic review, bupropion was as effective as methylphenidate for ADHD patients. Additionally, tolerability and acceptability were also comparable. However, these findings should be considered as very preliminary results. To confirm this evidence, further studies in this area should be conducted. PMID- 25120367 TI - Double-balloon tamponade in the management of postpartum hemorrhage: a case series. AB - To show the efficacy of double-balloon cervical ripening catheter in the management of postpartum hemorrhage originating from the lower segment of the uterus or the upper parts of the vagina. METHODS: Patients with intractable bleeding from the lower segment of the uterus and the upper parts of the vagina after Cesarean or vaginal deliveries were treated by double-balloon cervical ripening catheter. RESULTS: Double-balloon catheter was used in seven patients, and it was properly placed in all of them. No other intervention was needed to control bleeding. Two patients were delivered vaginally, and five patients were delivered by Cesarean section. Length of hospitalization was longer in the vaginal delivery patients (average hospitalization was 12 days in the vaginal delivery patients and 5 days in the Cesarean section patients). The need for blood and blood products transfusion (average of blood and blood products transfusion was 30 U in the vaginal delivery patients and 6 U in the Cesarean patients) was also higher in the vaginal delivery patients. CONCLUSION: Although double-balloon cervical ripening catheter is designed for the induction of labor, it can successfully control intractable bleedings from the lower segment of the uterus and the upper parts of the vagina. This procedure can save patients from undergoing more morbid procedures. PMID- 25120368 TI - Clinical utility of the neutrophil elastase inhibitor sivelestat for the treatment of acute respiratory distress syndrome. AB - Acute respiratory distress syndrome is a serious condition that can arise following direct or indirect lung injury. It is heterogeneous and has a high mortality rate. Supportive care is the mainstay of treatment and there is no definitive pharmacological treatment as yet. Sivelestat is a neutrophil elastase inhibitor approved in Japan and the Republic of Korea for acute lung injury, including acute respiratory distress syndrome in patients with systemic inflammatory response syndrome. The aim of this review is to examine the clinical utility of sivelestat in different disease states, using data from nonclinical and clinical studies. In nonclinical studies, sivelestat appears to show benefit in acute lung injury without inhibiting the host immune defense in cases of infection. Clinical studies do not yet provide a clear consensus. Phase III and IV Japanese studies have shown improvements in pulmonary function, length of intensive care unit stay, and mechanical ventilation, but a non-Japanese multicenter study did not demonstrate sivelestat to have an effect on ventilator free days or 28-day all-cause mortality. Evidence of improvement in various parameters, including duration of stay in intensive care, mechanical ventilation, the ratio of partial pressure of arterial oxygen and fraction of inspired oxygen (PaO2/FIO2 ratio) ratio, and lung injury scores, has been shown in patients with sepsis or gastric aspiration, and following the surgical treatment of esophageal cancer. To date, there are no particular concerns regarding adverse events, and the available data do not suggest that sivelestat might worsen infections. One study has analyzed cost-effectiveness, finding that sivelestat may reduce costs compared with standard care. The currently available evidence suggests that sivelestat may show some benefit in the treatment of acute lung injury/acute respiratory distress syndrome, although large, randomized controlled trials are needed in specific pathophysiological conditions to explore these potential benefits. PMID- 25120369 TI - Impact of pharmacist interventions on drug-related problems and laboratory markers in outpatients with human immunodeficiency virus infection. AB - BACKGROUND: Substantial complexity has been introduced into treatment regimens for patients with human immunodeficiency virus (HIV) infection. Many drug-related problems (DRPs) are detected in these patients, such as low adherence, therapeutic inefficacy, and safety issues. We evaluated the impact of pharmacist interventions on CD4+ T-lymphocyte count, HIV viral load, and DRPs in patients with HIV infection. METHODS: In this 18-month prospective controlled study, 90 outpatients were selected by convenience sampling from the Hospital Dia University of Campinas Teaching Hospital (Brazil). Forty-five patients comprised the pharmacist intervention group and 45 the control group; all patients had HIV infection with or without acquired immunodeficiency syndrome. Pharmaceutical appointments were conducted based on the Pharmacotherapy Workup method, although DRPs and pharmacist intervention classifications were modified for applicability to institutional service limitations and research requirements. Pharmacist interventions were performed immediately after detection of DRPs. The main outcome measures were DRPs, CD4+ T-lymphocyte count, and HIV viral load. RESULTS: After pharmacist intervention, DRPs decreased from 5.2 (95% confidence interval [CI] =4.1-6.2) to 4.2 (95% CI =3.3-5.1) per patient (P=0.043). A total of 122 pharmacist interventions were proposed, with an average of 2.7 interventions per patient. All the pharmacist interventions were accepted by physicians, and among patients, the interventions were well accepted during the appointments, but compliance with the interventions was not measured. A statistically significant increase in CD4+ T-lymphocyte count in the intervention group was found (260.7 cells/mm(3) [95% CI =175.8-345.6] to 312.0 cells/mm(3) [95% CI =23.5-40.6], P=0.015), which was not observed in the control group. There was no statistical difference between the groups regarding HIV viral load. CONCLUSION: This study suggests that pharmacist interventions in patients with HIV infection can cause an increase in CD4+ T-lymphocyte counts and a decrease in DRPs, demonstrating the importance of an optimal pharmaceutical care plan. PMID- 25120366 TI - Clinical and economic studies of eptifibatide in coronary stenting. AB - Platelet adhesion and aggregation at the site of coronary stenting can have catastrophic clinical and economic consequences. Therefore, effective platelet inhibition is vital during and after percutaneous coronary intervention. Eptifibatide is an intravenous antiplatelet agent that blocks the final common pathway of platelet aggregation and thrombus formation by binding to glycoprotein IIb/IIIa receptors on the surface of platelets. In clinical studies, eptifibatide was associated with a significant reduction of mortality, myocardial infarction, or target vessel revascularization in patients with acute coronary syndrome undergoing percutaneous coronary intervention. However, recent trials conducted in the era of dual antiplatelet therapy and newer anticoagulants failed to demonstrate similar results. The previously seen favorable benefit of eptifibatide was mainly offset by the increased risk of bleeding. Current American College of Cardiology/American Heart Association guidelines recommend its use as an adjunct in high-risk patients who are undergoing percutaneous coronary intervention with traditional anticoagulants (heparin or enoxaparin), who are not otherwise at high risk of bleeding. In patients receiving bivalirudin (a newer safer anticoagulant), routine use of eptifibatide is discouraged except in select situations (eg, angiographic complications). Although older pharmacoeconomic studies favor eptifibatide, in the current era of P2Y12 inhibitors and newer safer anticoagulants, the increased costs associated with bleeding make the routine use of eptifibatide an economically nonviable option. The cost-effectiveness of eptifibatide with the use of strategies that decrease the bleeding risk (eg, transradial access) is unknown. This review provides an overview of key clinical and economic studies of eptifibatide well into the current era of potent antiplatelet agents, novel safer anticoagulants, and contemporary percutaneous coronary intervention. PMID- 25120370 TI - The difficulties of interprofessional teamwork in diabetes care: a questionnaire survey. AB - BACKGROUND: Diabetes is a multifactorial disease and its nature means that interprofessional teamwork is essential for its treatment. However, in general, interprofessional teamwork has certain problems that impede its function. To clarify these problems in relation to diabetes care, a questionnaire survey was conducted. METHODS: The participants who were involved in diabetes-related educational seminars, and medical personnel who were engaged in diabetes care from the National Center for Global Health and Medicine, were asked to complete the questionnaire about perceptions of, and satisfaction with, interprofessional teamwork across multiple health care providers, who were actually involved in diabetes care. RESULTS: From 456 people who were asked to take the questionnaire, 275 people answered. The percentages of the respondents according to profession who considered multidisciplinary teamwork sufficient were as follows: physicians, 20.5%; nurses, 12.7%; registered dietitians, 29.6%; pharmacists, 21.9%; physiotherapists, 18.2%; and clinical laboratory technicians 15.4%. Insufficient interprofessional communication and inconsistency in motivation levels among staff were frequently cited as causes of insufficient teamwork. All professions considered interprofessional meetings or conferences necessary and essential for teamwork. CONCLUSION: The survey revealed that interprofessional teamwork in diabetes care is currently insufficient. Continuous efforts to change each profession's perceptions about interprofessional teamwork and efforts to improve the quality of interprofessional meetings are necessary. PMID- 25120371 TI - Silencing B7-H1 enhances the anti-tumor effect of bladder cancer antigen-loaded dendritic cell vaccine in vitro. AB - OBJECTIVE: The aim of this study was to examine whether short hairpin RNA (shRNA) expressing lentiviral particles targeting B7-H1 infection could result in B7-H1 knockdown on dendritic cells (DCs) and to investigate whether B7-H1 silencing could augment the immune function of DCs and further elicit a more potent anti tumor immune effect against bladder cancer cells in vitro. METHODS: Monocyte derived DCs, which were generated from peripheral blood mononuclear cells, were infected by a recombinant lentivirus containing shRNA sequence aimed at B7-H1. After that, the infected DCs were pulsed by tumor antigens and used to stimulate cytotoxic T lymphocytes-based anti-tumor effect in vitro. RESULTS: The lentivirus mediated shRNA delivery method efficiently and effectively silenced B7-H1 in DCs. Furthermore, the B7-H1 silencing enhanced the stimulatory capacity and the secretion of interleukin-12, but down-regulated interleukin-10 secretion. And more importantly, the anti-tumor effect of bladder cancer antigen-loaded DC vaccine in vitro was also potentially augmented. CONCLUSION: This study suggests that a combination of B7-H1 knockdown and target antigen delivery could augment anti-tumor effects in vitro, which potentially provides a novel strategy in the immunotherapy of bladder cancer. PMID- 25120372 TI - PKN1 modulates TGFbeta and EGF signaling in HEC-1-A endometrial cancer cell line. AB - BACKGROUND: The response of cells to TGFbeta and EGF is mediated by a network of various intracellular regulators. The signaling crosstalk between different regulators is of key importance for tumorigenesis. The crosstalk may explain the modulation of cellular responses to the same regulator by another signaling molecule. As PKN1 - a serine/threonine kinase implicated in tumorigenesis - was identified as potential crosstalk node for TGFbeta and EGF signaling, the cellular functions that may be affected by PKN1 in a crosstalk of TGFbeta and EGF were explored. METHODS: To investigate the contribution of PKN1 to TGFbeta and EGF signaling, transiently PKN1-transfected HEC-1-A endometrial cancer cells were generated and subjected to treatment with TGFbeta1, EGF, and their combination. Proliferation, apoptosis, invasion, wound healing, and migration assays were performed. The impact of PKN1 on the expression and phosphorylation of intracellular proteins was monitored by immunoblotting. RESULTS: It was demonstrated that PKN1 modulated the responses of HEC-A-1 endometrial cancer cells to TGFbeta1 and EGF. PKN1 had an inhibitory effect on the stimulation of cell migration, and PKN1 kinase activity was required for the inhibitory effect of TGFbeta and EGF on cell proliferation and invasiveness. It was observed that phosphorylation of Smad2, FAK, and Erk1/2 correlated with responses of the cells to TGFbeta1 and EGF. CONCLUSION: PKN1 modulates TGFbeta- and EGF-dependent regulation of cell proliferation, migration, and invasiveness, and therefore is a component of the network signaling downstream of TGFbeta and EGF. PMID- 25120373 TI - A community-based exercise intervention transitions metabolically abnormal obese adults to a metabolically healthy obese phenotype. AB - BACKGROUND: Lower habitual physical activity and poor cardiorespiratory fitness are common features of the metabolically abnormal obese (MAO) phenotype that contribute to increased cardiovascular disease risk. The aims of the present study were to determine 1) whether community-based exercise training transitions MAO adults to metabolically healthy, and 2) whether the odds of transition to metabolically healthy were larger for obese individuals who performed higher volumes of exercise and/or experienced greater increases in fitness. METHODS AND RESULTS: Metabolic syndrome components were measured in 332 adults (190 women, 142 men) before and after a supervised 14-week community-based exercise program designed to reduce cardiometabolic risk factors. Obese (body mass index >=30 kg . m(2)) adults with two to four metabolic syndrome components were classified as MAO, whereas those with no or one component were classified as metabolically healthy but obese (MHO). After community exercise, 27/68 (40%) MAO individuals (P<0.05) transitioned to metabolically healthy, increasing the total number of MHO persons by 73% (from 37 to 64). Compared with the lowest quartiles of relative energy expenditure and change in fitness, participants in the highest quartiles were 11.6 (95% confidence interval: 2.1-65.4; P<0.05) and 7.5 (95% confidence interval: 1.5-37.5; P<0.05) times more likely to transition from MAO to MHO, respectively. CONCLUSION: Community-based exercise transitions MAO adults to metabolically healthy. MAO adults who engaged in higher volumes of exercise and experienced the greatest increase in fitness were significantly more likely to become metabolically healthy. Community exercise may be an effective model for primary prevention of cardiovascular disease. PMID- 25120374 TI - Diabetes disease progression in Goto-Kakizaki rats: effects of salsalate treatment. AB - This study investigates the antidiabetic effects of salsalate on disease progression of diabetes in non-obese diabetic Goto-Kakizaki (GK) rats, an experimental model of type 2 diabetes. Salsalate was formulated in rat chow (1,000 ppm) and used to feed rats from 5 to 21 weeks of age. At 5 weeks of age, GK and Wistar (WIS) control rats were subdivided into four groups, each composed of six rats: GK rats with standard diet (GK-C); GK rats with salsalate-containing diet (GK-S); WIS rats with standard diet (WIS-C); and WIS rats with salsalate containing diet (WIS-S). The GK-C rats (167.2+/-11.6 mg/dL) showed higher blood glucose concentrations than WIS-C rats (133.7+/-4.9 mg/dL, P<0.001) at the beginning of the experiment, and had substantially elevated blood glucose from an age of 15 weeks until sacrifice at 21 weeks (341.0+/-133.6 mg/dL). The GK-S rats showed an almost flat profile of blood glucose from 4 weeks (165.1+/-11.0 mg/dL) until sacrifice at 21 weeks of age (203.7+/-22.2 mg/dL). While this difference in blood glucose between 4 and 21 weeks in GK-S animals was significant, blood glucose at 21 weeks was significantly lower in GK-S compared to GK-C animals. At sacrifice, salsalate decreased plasma insulin (GK-S =1.0+/-0.3; GK-C =2.0+/-0.3 ng/mL, P<0.001) and increased plasma adiponectin concentrations (GK-S =15.9+/ 0.7; GK-C =9.7+/-2.0 MUg/mL, P<0.001). Salsalate also lowered total cholesterol in GK-S rats (96.1+/-8.5 mg/dL) compared with GK-C rats (128.0+/-11.4 mg/dL, P<0.001). Inflammation-related genes (Ifit1 and Iigp1) exhibited much higher mRNA expression in GK-C rats than WIS-C rats in liver, adipose, and muscle tissues, while salsalate decreased the Ifit1 and Iigp1 mRNA only in adipose tissue. These results suggest that salsalate acts to both increase adiponectin and decrease adipose tissue-based inflammation while preventing type 2 diabetes disease progression in GK rats. PMID- 25120375 TI - Transdermal fentanyl patch for postoperative analgesia in total knee arthroplasty: a randomized double-blind controlled trial. AB - PURPOSE: To assess the efficacy of a transdermal fentanyl patch (TFP) (50 MUg/hour) applied 10-12 hours before surgery versus placebo for postoperative pain control of total knee arthroplasty (TKA). MATERIALS AND METHODS: We enrolled 40 patients undergoing elective TKA under spinal anesthesia using isobaric or hyperbaric bupivacaine. Subjects were randomized to receive a TFP (Duragesic((r)) 50 MUg/hour) or placebo patch applied with a self-adhesive to the anterior chest wall 10-12 hours before spinal anesthesia. Every patient was given patient controlled morphine for postoperative pain control. Patients were evaluated every 4 hours until 48 hours. RESULTS: Morphine consumption at 24 and 48 hours in the TFP group versus the placebo group was 15.40+/-12.65 and 24.90+/-20.11 mg versus 33.60+/-19.06 and 57.80+/-12.65 mg (P<=0.001). Numeric rating scale scores at rest and during movement over 48 hours were lower in the TFP group. Ambulation and nausea/vomiting scores were statistically greater, but not clinically significant in the TFP group. Sedation scores were low and not statistically significantly different between groups. There was no severe respiratory depression. CONCLUSION: TFP (50 MUg/hour) applied 10-12 hours before surgery can effectively and safely decrease morphine consumption and pain scores during the first 48 hours after TKA surgery. PMID- 25120378 TI - "One for all and all for one": consensus-building within communities in rural India on their health microinsurance package. AB - INTRODUCTION: This study deals with consensus by poor persons in the informal sector in rural India on the benefit-package of their community-based health insurance (CBHI). In this article we describe the process of involving rural poor in benefit-package design and assess the underlying reasons for choices they made and their ability to reach group consensus. METHODS: The benefit-package selection process entailed four steps: narrowing down the options by community representatives, plus three Choosing Healthplans All Together (CHAT) rounds conducted among female members of self-help groups. We use mixed-methods and four sources of data: baseline study, CHAT exercises, in-depth interviews, and evaluation questionnaires. We define consensus as a community resolution reached by discussion, considering all opinions, and to which everyone agrees. We use the coefficient of unalikeability to express consensus quantitatively (as variability of categorical variables) rather than just categorically (as a binomial Yes/No). FINDINGS: The coefficient of unalikeability decreased consistently over consecutive CHAT rounds, reaching zero (ie, 100% consensus) in two locations, and confirmed gradual adoption of consensus. Evaluation interviews revealed that the wish to be part of a consensus was dominant in all locations. The in-depth interviews indicated that people enjoyed the participatory deliberations, were satisfied with the selection, and that group decisions reflected a consensus rather than majority. Moreover, evidence suggests that pre-selectors and communities aimed to enhance the likelihood that many households would benefit from CBHI. CONCLUSION: The voluntary and contributory CBHI relies on an engaging experience with others to validate perceived priorities of the target group. The strongest motive for choice was the wish to join a consensus (more than price or package-composition) and the intention that many members should benefit. The degree of consensus improved with iterative CHAT rounds. Harnessing group consensus requires catalytic intervention, as the process is not spontaneous. PMID- 25120377 TI - Spiritual and religious aspects of skin and skin disorders. AB - Skin and skin disorders have had spiritual aspects since ancient times. Skin, hair, and nails are visible to self and others, and touchable by self and others. The skin is a major sensory organ. Skin also expresses emotions detectable by others through pallor, coldness, "goose bumps", redness, warmth, or sweating. Spiritual and religious significances of skin are revealed through how much of the skin has been and continues to be covered with what types of coverings, scalp and beard hair cutting, shaving and styling, skin, nail, and hair coloring and decorating, tattooing, and intentional scarring of skin. Persons with visible skin disorders have often been stigmatized or even treated as outcasts. Shamans and other spiritual and religious healers have brought about healing of skin disorders through spiritual means. Spiritual and religious interactions with various skin disorders such as psoriasis, leprosy, and vitiligo are discussed. Religious aspects of skin and skin diseases are evaluated for several major religions, with a special focus on Judaism, both conventional and kabbalistic. PMID- 25120379 TI - Empathy levels among first year Malaysian medical students: an observational study. PMID- 25120376 TI - Noncontraceptive benefits of the estradiol valerate/dienogest combined oral contraceptive: a review of the literature. AB - Combined oral contraceptives formulated to include estradiol (E2) have recently become available for the indication of pregnancy prevention. A combined estradiol valerate and dienogest pill (E2V/DNG), designed to be administered using an estrogen step-down and a progestin step-up regimen over 26 days of active treatment followed by 2 days of placebo (26/2-day regimen), has also undergone research to assess the potential for additional noncontraceptive benefits. Randomized, placebo-controlled studies have demonstrated that E2V/DNG is an effective treatment for heavy menstrual bleeding - a reduction in median menstrual blood loss approaching 90% occurs after 6 months of treatment. To date, E2V/DNG is the only oral contraceptive approved for this indication. Comparator studies have also demonstrated a reduction in hormone withdrawal-associated symptoms in users of E2V/DNG compared with a conventional 21/7-day regimen of ethinylestradiol/levonorgestrel. Other potential noncontraceptive benefits associated with E2V/DNG, like improvement in dysmenorrhea, sexual function, and quality of life, are comparable with those associated with other combined oral contraceptives and are discussed further in this review. PMID- 25120380 TI - Primary healthcare system and practice characteristics in Singapore. AB - It is crucial to adapt and improve the (primary) health care systems of countries to prepare for future patient profiles and their related needs. The main aim of this study was to acquire a comprehensive overview of the perceptions of primary care experts in Singapore about the state of primary care in Singapore, and to compare this with the state of primary care in other countries. Notwithstanding ranked 2(nd) in terms of efficiency of health care, Singapore is facing significant health care challenges. Emails were sent to 85 experts, where they were asked to rate Singapore's primary care system based on nine internationally adopted health system characteristics and six practice characteristics (response rate = 29%). The primary care system in Singapore received an average of 10.9 out of 30 possible points. Lowest ratings were given to: earnings of primary care physicians compared to specialists, requirement for 24 hr accessibility of primary care services, standard of family medicine in academic departments, reflection of community served by practices in patient lists, and the access to specialists without needing to be referred by primary care physicians. Singapore was categorized as a 'low' primary care country according to the experts. PMID- 25120381 TI - An exploration of self-management support in the context of palliative nursing: a modified concept analysis. AB - BACKGROUND: The role of self-management is often ambiguous, yet, it is an important area in clinical practice for palliative nurses. A clear conceptual understanding, however, of what it represents is lacking. METHOD: This paper reports an analysis of the concept of self-management support in palliative nursing. Avant and Walker's method was used to guide this concept analysis. A search of electronic databases (1990-2013), use of internet search engines and supplementary hand searching produced an international data set of reviews, empirical research, editorials, protocols and guidelines. RESULTS: Based on the analysis self-management support in palliative nursing has been defined as assessing, planning, and implementing appropriate care to enable the patient to live until they die and supporting the patient to be given the means to master or deal with their illness or their effects of their illness themselves. CONCLUSIONS: Clarity with the concept of self-management support and palliative nursing could enable nurses to provide more patient and family centred care to people facing life threatening illnesses. PMID- 25120382 TI - Metformin inhibition of neuroblastoma cell proliferation is differently modulated by cell differentiation induced by retinoic acid or overexpression of NDM29 non coding RNA. AB - BACKGROUND: Metformin is a widely used oral hypoglycemizing agent recently proposed as potential anti-cancer drug. In this study we report the antiproliferative effect of metformin treatment in a high risk neuroblastoma cell model, focusing on possible effects associated to different levels of differentiation and/or tumor initiating potential. METHODS: Antiproliferative and cytotoxic effects of metformin were tested in human SKNBE2 and SH-SY5Y neuroblastoma cell lines and in SKNBE2 cells in which differentiation is induced by retinoic acid treatment or stable overexpression of NDM29 non-coding RNA, both conditions characterized by a neuron-like differentiated phenotype. RESULTS: We found that metformin significantly inhibits the proliferation of NB cells, an effect that correlates with the inhibition of Akt, while AMPK activity resulted unchanged. Notably, metformin effects were modulated in a different ways by differentiating stimuli, being abolished after retinoic acid treatment but potentiated by overexpression of NDM29. CONCLUSION: These data suggest the efficacy of metformin as neuroblastoma anticancer agent, and support the requirement of further studies on the possible role of the differentiation status on the antiproliferative effects of this drug. PMID- 25120385 TI - The in-hospital consultation today: whom does it best serve? PMID- 25120383 TI - New strategy to control cell migration and metastasis regulated by CCN2/CTGF. AB - Connective tissue growth factor (CTGF)/CCN family member 2 (CCN2) is a CCN family member of matricellular signaling modulators. It has been shown that CCN2/CTGF mediates cell adhesion, aggregation and migration in a large variety of cell types, including vascular endothelial cells, fibroblasts, epithelial cells, aortic smooth muscle and also pluripotent stem cells. Others matricellular proteins are capable of interacting with CCN2/CTGF to mediate its function. Cell migration is a key feature for tumor cell invasion and metastasis. CCN2/CTGF seems to be a prognostic marker for cancer. In addition, here we intend to discuss recent discoveries and a new strategy to develop therapies against CCN2/CTGF, in order to treat cancer metastasis. PMID- 25120386 TI - The man in the waiting room. PMID- 25120384 TI - hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by targeting NOV/CCN3. AB - BACKGROUND: For treatment and prevention of metastatic disease, one of the premier challenges is the identification of pathways and proteins to target for clinical intervention. Micro RNAs (miRNAs) are short, non-coding RNAs, which regulate cellular activities by either mRNA degradation or translational inhibition. Our studies focused on the invasive properties of hsa-mir30c based on its high expression in MDA-MB-231 metastatic cells and our bioinformatic analysis of the Cancer Genome Atlas that identified aberrant hsa-mir-30c to be associated with poor survival. METHODS: Contributions of hsa-mir-30c to breast cancer cell invasion were examined by Matrigel invasion transwell assays following modulation of hsa-mir-30c or hsa-mir-30c* levels in MDA-MB-231 cells. hsa-mir-30c in silico predicted targets linked to cell invasion were screened for targeting by hsa-mir 30c in metastatic breast cancer cells by RT-qPCR. The contribution to invasion by a target of hsa-mir-30c, Nephroblastoma overexpressed (NOV), was characterized by siRNA and invasion assays. Significant effects were determined using Student's T tests with Welch's correction for unequal variance. RESULTS: MCF-7 and MDA-MB-231 cells were used as models of poorly invasive and late-stage metastatic disease, respectively. By modulating the levels of hsa-mir-30c in these cells, we observed concomitant changes in breast cancer cell invasiveness. From predicted targets of hsa-mir-30c that were related to cellular migration and invasion, NOV/CCN3 was identified as a novel target of hsa-mir-30c. Depleting NOV by siRNA caused a significant increase in the invasiveness of MDA-MB-231 cells is a regulatory protein associated with the extracellular matrix. CONCLUSIONS: NOV/CCN3 expression, which protects cells from invasion, is known in patient tumors to inversely correlate with advanced breast cancer and metastasis. This study has identified a novel target of hsa-mir-30c, NOV, which is an inhibitor of the invasiveness of metastatic breast cancer cells. Thus, hsa-mir-30c-mediated inhibition of NOV levels promotes the invasive phenotype of MDA-MB-231 cells and significantly, the miR-30/NOV pathways is independent of RUNX2, a known target of hsa-mir-30c that promotes osteolytic disease in metastatic breast cancer cells. Our findings allow for mechanistic insight into the clinical observation of poor survival of patients with elevated hsa-mir-30c levels, which can be considered for miRNA-based translational studies. PMID- 25120387 TI - Percutaneous closure versus medical therapy alone for cryptogenic stroke patients with a patent foramen ovale: meta-analysis of randomized controlled trials. AB - Of cryptogenic stroke patients younger than 55 years of age, up to 61% have had a patent foramen ovale (PFO). Observational studies have revealed reductions in recurrent neurologic events through PFO closure versus medical therapy, and randomized controlled trials have shown nonsignificant trends toward benefit. We systematically searched for randomized controlled trials of percutaneous PFO closure with medical therapy versus medical therapy alone in patients with cryptogenic stroke and performed a meta-analysis of treatment outcomes. The primary endpoint was combined death, stroke, and transient ischemic attack. We included 3 trials. Of 2,303 total patients, 1,150 underwent PFO closure and 1,153 received medical therapy (median follow-up period, 2.6 yr). The pooled incidence of the primary endpoint was 1.2 events per 100 patient-years in the closure group (95% confidence interval [CI], 0.2-2.3) and 1.8 in the therapy group (95% CI, 0.7 2.9) (P=0.32); the number needed to treat was 167 (range, 100-500). The corresponding pooled hazard ratio was 0.67 (95% CI, 0.44-1.01; P=0.054) in favor of closure. Closure was associated with an increased risk of atrial fibrillation: relative risk=3.51 (95% CI, 1.44-8.55; P=0.006). When stratified by device, use of the AmplatzerTM PFO Occluder resulted in significant stroke-prevention benefit over medical therapy alone: hazard ratio=0.44 (95% CI, 0.21-0.95; P=0.037). When compared with medical therapy alone, PFO closure with medical therapy showed a trend toward a decreased hazard of combined events, although the absolute event reduction was small and the number needed to treat was high. PMID- 25120388 TI - Abdominal fat suspension device for maintaining normal cardiorespiratory function in patients undergoing conscious sedation during surgery: a feasibility study. AB - Obese patients undergoing conscious-sedation surgery have increased perioperative morbidity because their excess abdominal tissue limits diaphragmatic excursion. We describe a simple device that might help attenuate this risk. We created a noninvasive suction device for abdominal suspension. By lifting the burden of excess weight, this device should decrease respiratory effort. To test the feasibility of excess weight removal in relieving cardiac stress, we tested 22 supine, healthy, normal-weight subjects by measuring their heart rates with and without a 13-kg tissue model on their abdomen to simulate excess weight. There was no significant difference in blood oxygen saturation before and after weight removal (P=0.318). However, the decrease in heart rate was significant (P <0.0001; paired 2-sample, one-tailed t test), which implies decreased respiratory effort. This result suggests the possibility that abdominal mass suspension in obese patients is associated with decreased respiratory effort. PMID- 25120389 TI - Use of oversized injectable valves in growing children for total repair of right ventricular outflow tract anomalies (preliminary results). AB - Right ventricular outflow tract surgery was originally confined to transannular patching, in the belief that pulmonary regurgitation was well tolerated. Because follow-up evaluations revealed the deleterious effects of pulmonary regurgitation, surgery today aims to spare or replace the valve. Available replacement devices have short lifetimes, considering growth mismatch in children. We hypothesize that oversizing the right infundibulum anticipates growth and that a squeezed prosthesis can complete the expansion process. The No React(r) Injectable BioPulmonic Valve is designed for right infundibular surgery in adults, and hundreds of implants have shown promising results. We used this device for surgery in babies, with the addition of an innovative oversizing technique. This study evaluates our preliminary results and investigates whether such a technique might reduce growth mismatch. From September 2010 through July 2012, we implanted 11 injectable pulmonic valves. The median age of our patients was 23 months. After opening the right infundibulum, we enlarged it as much as possible with a wide patch. Before completing the patch suture, we injected an oversized valve. No problems occurred during surgery. No major insufficiency or leak was observed. We conclude that prostheses can be quite oversized and perform well even when not completely expanded. Oversized injectable pulmonic valves, shrunken to a smaller diameter, enabled the implantation of a device wider than otherwise possible, without affecting performance. Moreover, the prosthesis tended to return to its original size following growth, thereby reducing growth mismatch. Longer follow-up and larger numbers of patients are needed for verification. PMID- 25120390 TI - Left ventricular remodeling after late revascularization correlates with baseline viability. AB - The ideal management of stable patients who present late after acute ST-elevation myocardial infarction (STEMI) is still a matter of conjecture. We hypothesized that the extent of improvement in left ventricular function after successful revascularization in this subset was related to the magnitude of viability in the infarct-related artery territory. However, few studies correlate the improvement of left ventricular function with the magnitude of residual viability in patients who undergo percutaneous coronary intervention in this setting. In 68 patients who presented later than 24 hours after a confirmed first STEMI, we performed resting, nitroglycerin-enhanced, technetium-99m sestamibi single-photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI) before percutaneous coronary intervention, and again 6 months afterwards. Patients whose baseline viable myocardium in the infarct-related artery territory was more than 50%, 20% to 50%, and less than 20% were divided into Groups 1, 2, and 3 (mildly, moderately, and severely reduced viability, respectively). At follow-up, there was significant improvement in end-diastolic volume, end-systolic volume, and left ventricular ejection fraction in Groups 1 and 2, but not in Group 3. We conclude that even late revascularization of the infarct-related artery yields significant improvement in left ventricular remodeling. In patients with more than 20% viable myocardium in the infarct-related artery territory, the extent of improvement in left ventricular function depends upon the amount of viable myocardium present. The SPECT-MPI can be used as a guide for choosing patients for revascularization. PMID- 25120391 TI - Heart failure in remission for more than 13 years after removal of a left ventricular assist device. AB - Mechanical cardiac unloading with use of a left ventricular assist device (LVAD) is associated with substantial improvements in left ventricular function and enables subsequent LVAD explantation in some patients. We describe the case of a 35-year-old man with dilated nonischemic cardiomyopathy who was supported with an LVAD for 9 months. After the device was removed, he led a normal life for 13 years and 4 months. However, at 49 years of age, he presented with new signs and symptoms of heart failure, necessitating implantation of a 2nd LVAD. Afterwards, he has remained asymptomatic. This case is unique in that the patient lived a normal life for longer than a decade before renewed left ventricular decompensation necessitated repeat LVAD therapy. Histologic examination revealed few changes between the first device's removal in 1999 and the 2nd device's implantation in 2012. PMID- 25120392 TI - Myxoma of the left ventricle. AB - This report concerns a 69-year-old woman who presented with an asymptomatic myxoma in the left ventricle. The tumor was successfully excised. We provide a very brief review of 72 other published cases of surgically treated left ventricular myxoma. PMID- 25120393 TI - Nontyphoidal cardiac salmonellosis: two case reports and a review of the literature. AB - Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of endocarditis and pericarditis that carries a high mortality rate. Proposed predisposing conditions include immunodeficiency states, congenital heart defects, and cardiac valve diseases. We present 2 cases of cardiovascular salmonellosis. The first case is that of a 73-year-old woman with mechanical mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second case is that of a 62-year-old man with a recent systemic lupus erythematosus exacerbation treated with oral steroids, who presented with obstructive features of tamponade and sepsis secondary to a large S. enteritidis purulent pericardial cyst. He recovered after emergent pericardial drainage and antibiotic therapy. Identifying patients at risk of cardiovascular salmonellosis is important for early diagnosis and treatment to minimize sequelae and death. We reviewed the literature to identify the predisposing risk factors of nontyphoidal Salmonella cardiac infection. PMID- 25120394 TI - Left ventricular aneurysm repair with use of a bovine pericardial patch. AB - Left ventricular aneurysm, which can impair systolic function, has a reported incidence of 10% to 35% in patients after myocardial infarction. In a 58-year-old woman who had a history of myocardial infarction, we excised a large left ventricular aneurysm and restored left ventricular geometry with use of a bovine pericardial patch. The aneurysm's characteristics and the patient's preoperative left ventricular ejection fraction of 0.25 had indicated surgical intervention. The patient had an uneventful postoperative course, and her left ventricular ejection fraction was 0.50 to 0.55 on the 4th postoperative day. This case illustrates the value of surgical treatment for patients who have a debilitating left ventricular aneurysm. PMID- 25120395 TI - Coarctation of persistent 5th aortic arch: first report of catheter-based intervention. AB - Persistent 5th aortic arch, originally called double-lumen aortic arch, is a rarely reported cardiac developmental anomaly that results in systemic-to systemic or systemic-to-pulmonary shunting. When this malformation occurs, other intracardiac defects are almost always present. We report the case of a 7-month old girl who presented with a heart murmur; she was found to have an interrupted 4th aortic arch and coarctation of a persistent 5th aortic arch, with no other defects. To our knowledge, this is the 3rd report of a pediatric patient with this condition in isolation, and the first report of its diagnosis and treatment by means of cardiac catheterization and balloon angioplasty. PMID- 25120396 TI - Left main coronary artery obstruction by dislodged native-valve calculus after transcatheter aortic valve replacement. AB - Transcatheter aortic valve replacement can be an effective, reliable treatment for severe aortic stenosis in surgically high-risk or ineligible patients. However, various sequelae like coronary artery obstruction can occur, not only in the long term, but also immediately after the procedure. We present the case of a 78-year-old woman whose left main coronary artery became obstructed with calculus 2 hours after the transfemoral implantation of an Edwards Sapien XT aortic valve. Despite percutaneous coronary intervention in that artery, the patient died. This case reminds us that early recognition of acute coronary obstruction and prompt intervention are crucial in patients with aortic stenosis who have undergone transcatheter aortic valve replacement. PMID- 25120397 TI - Cor triatriatum dexter and atrial septal defect in a 43-year-old woman. AB - Cor triatriatum dexter is a rare congenital heart anomaly in which a membrane divides the right atrium into 2 chambers. We report the case of a 43-year-old woman who had cor triatriatum dexter and a large atrial septal defect. During attempted percutaneous closure, the balloon disrupted the membrane and revealed that the defect had no inferior rim, precluding secure placement of an Amplatzer Septal Occluder. Surgical treatment subsequently proved to be successful. In patients with an incomplete membrane and a septal defect with well-defined rims, percutaneous treatment can be the first choice. In patients who have cor triatriatum dexter and unfavorable anatomic features or concomitant complex heart anomalies, open-heart surgery remains the gold standard for treatment. PMID- 25120398 TI - Concomitant reconstruction of arch vessels during repair of aortic dissection. AB - Surgery for acute aortic dissection is challenging, especially in cases of cerebral malperfusion. Should we perform only the aortic repair, or should we also reconstruct the arch vessels when they are severely affected by the disease process? Here we present a case of acute aortic dissection with multiple tears that involved the brachiocephalic artery and caused cerebral and right upper extremity malperfusion. The patient successfully underwent complete replacement of the brachiocephalic artery and the aortic arch during deep hypothermic circulatory arrest, with antegrade cerebral protection. We have found this technique to be safe and reproducible for use in this group of patients. PMID- 25120399 TI - Right ventricular outflow tract obstruction caused by double-chambered right ventricle presenting in adulthood. AB - Congenital heart diseases that cause obstruction of the right ventricular outflow tract are often difficult to diagnose. We report the case of a 49-year-old man who presented with long-standing shortness of breath on exertion. Imaging revealed right ventricular outflow tract obstruction caused by a double-chambered right ventricle, and he was referred for surgical correction. This case emphasizes both the detailed perioperative evaluation that is needed when diagnosing adults who present with manifestations of congenital heart disease and a method of successful surgical correction that resulted in symptom resolution. PMID- 25120400 TI - Penetrating nail-gun injury of the heart managed by adenosine-induced asystole in the absence of a heart-lung machine. AB - During his work, an 18-year-old carpenter-in-training overbalanced and shot himself in the left median thorax with a nail gun. The patient was delivered to our thoracic surgery unit with a tentative diagnosis of penetrating lung trauma. An emergent computed tomogram showed a heart-penetrating nail injury. The patient was taken to the operating room, where he underwent emergency surgery that included sternotomy, pericardiotomy, extraction of the nail, and trauma treatment of the heart injury. The surgery was performed in a unit without a heart-lung machine. For that reason, asystole was chemically induced by the intravenous administration of adenosine. The surgery was successful, and the patient was discharged from the hospital on the 10th postoperative day. In cases of penetrating injuries of the heart, especially those with a foreign body retained in situ, we believe that the intravenous administration of adenosine is an elegant solution for the rapid provocation of asystole. In contrast to other methods, adenosine-induced asystole enables relatively safe myocardial manipulation in the absence of a cardiac surgical unit and a heart-lung machine. PMID- 25120402 TI - Septic coronary artery embolism treated with aspiration thrombectomy: case report and review of literature. AB - Coronary embolization is a potentially fatal sequela of endocarditis. We report a case of Candida endocarditis with septic embolism to the left anterior descending coronary artery. This embolism was successfully treated with aspiration thrombectomy followed by balloon angioplasty. The treatment of acute coronary syndrome in the presence of septic embolism is controversial. Aspiration thrombectomy has been performed in this situation before, and it appears to be safer and more feasible than is thrombolysis or percutaneous transluminal angioplasty. PMID- 25120401 TI - Intimal sarcoma in the aortic arch partially obstructing the aorta with metastasis to the brain. AB - Primary tumors of the aorta are rare entities. We report the unusual manifestation of an aortic intimal sarcoma that presented as a brain metastasis in a 56-year-old, otherwise healthy woman. After the brain mass had been resected, multiple imaging methods revealed pseudocoarctation and the primary tumor in the aortic arch. To our knowledge, this is the first report of the diagnosis of an aortic intimal sarcoma with use of real-time, 3-dimensional transesophageal echocardiography. PMID- 25120403 TI - Intraoperative surgical sealant application during cardiac defect repair. AB - Bleeding can occur as a sequela to cardiac surgery. Surgical products-such as conventional sutures and clips, and somewhat less conventional sealants-have been developed to prevent this event. Among these, CoSeal is a sealant used at our institution; here we report the cases of 2 patients in whom CoSeal was used successfully as either a supplement or an alternative to suture repair. This sealant was found to be useful in attaining hemostasis both in high-pressure ventricular repair and in the rupture of a friable coronary sinus adjacent to vital structures (in this instance, a left circumflex coronary artery). PMID- 25120404 TI - Left-atrial-appendage occluder migrates in an asymptomatic patient. AB - Percutaneous closure of the left atrial appendage (LAA) is a new approach to the prevention of cardioembolic events in patients with atrial fibrillation. We implanted an LAA occlusion device (AmplatzerTM Cardiac Plug) in a 70-year-old woman via a transseptal approach. Upon her discharge from the hospital, a transthoracic echocardiogram showed stable anchoring of the device; 6 months after implantation, a routine transthoracic echocardiogram revealed migration of the occluder into the left ventricular outflow tract, in the absence of symptoms. We surgically removed the device from the mitral subvalvular apparatus and closed the LAA with sutures. This case shows that percutaneous LAA occlusion can result in serious adverse events, including device migration in the absence of signs or symptoms; therefore, careful follow-up monitoring is mandatory. PMID- 25120405 TI - Finding a lost coronary stent months later with use of multimethod imaging. PMID- 25120406 TI - Commissural prolapse of the mitral valve identified on 3-dimensional transesophageal echocardiography. PMID- 25120407 TI - Association of left ventricular noncompaction with polycystic kidney disease as shown by cardiac magnetic resonance imaging. PMID- 25120408 TI - Acute paraplegia during weightlifting: an unusual vascular catastrophe. PMID- 25120409 TI - More on weightlifting injuries. PMID- 25120410 TI - Low-amplitude electrocardiogram in a patient with atrial fibrillation, direct current electrical cardioversion, and takotsubo cardiomyopathy. PMID- 25120412 TI - Yet another Bradford's law: new evidence on integrated care from Japan. PMID- 25120411 TI - Health related quality of life and parental perceptions of child vulnerability among parents of a child with juvenile idiopathic arthritis: results from a web based survey. AB - BACKGROUND: A chronic illness, such as Juvenile Idiopathic Arthritis (JIA), has an impact on the whole family, especially on parents caring for the ill child. Therefore the aim of this study is to evaluate parental Health Related Quality of Life (HRQOL) and parental perceptions of child vulnerability (PPCV) and associated variables in parents of a child with JIA. METHODS: Parents of all JIA patients (0-18 years) in Amsterdam, the Netherlands, were eligible. HRQOL was measured using the TNO-AZL Questionnaire (TAAQOL) and PPCV using the Child Vulnerability Scale (CVS). The HRQOL of parents of a child with JIA was compared to a norm population, and differences between parents of a child with JIA and active arthritis versus parents of a child with JIA without active arthritis were analyzed (ANOVA). For PPCV, parents of a child with JIA were compared to a norm population, including healthy and chronically ill children (Chi(2), Mann-Whitney U test). Variables associated with PPCV were identified by logistic regression analyses. RESULTS: 155 parents (87.5% mothers) completed online questionnaires. JIA parents showed worse HRQOL than parents of healthy children on one out of twelve domains: fine motor HRQOL (p < .001). Parents of children with active arthritis showed worse HRQOL regarding daily activities (p < .05), cognitive functioning (p < .01) and depressive emotions (p < .05) compared to parents of children without active arthritis. Parents of children with JIA perceived their child as more vulnerable than parents of a healthy child (p < .001) and parents of a chronically ill child (p < .001). Parents of children with active arthritis reported higher levels of PPCV (p < .05) than parents of children without active arthritis. A higher degree of functional disability (p < .01) and shorter disease duration (p < .05) were associated with higher levels of PPCV. CONCLUSION: The HRQOL of JIA parents was comparable to the HRQOL of parents of a healthy child. JIA parents of a child with active arthritis showed worse HRQOL than parents of a child without active arthritis. Parents perceived their child with JIA as vulnerable. PMID- 25120413 TI - Methodological development of the interactive INTERLINKS Framework for Long-term Care. AB - There is increasing international research into health and social care services for older people in need of long-term care (LTC), but problems remain with respect to acquiring robust comparative information to enable judgements to be made regarding the most beneficial and cost-effective approaches. The project 'INTERLINKS' ('Health systems and LTC for older people in Europe') funded by the EU 7th Framework programme was developed to address the challenges associated with the accumulation and comparison of evidence in LTC across Europe. It developed a concept and method to describe and analyse LTC and its links with the health and social care system through the accumulation of policy and practice examples on an interactive web-based framework for LTC. This paper provides a critical overview of the theoretical and methodological approaches used to develop and implement the INTERLINKS Framework for LTC, with the aim of providing some guidance to researchers in this area. INTERLINKS has made a significant contribution to knowledge but robust evidence and comparability across European countries remain problematic due to the current and growing complexity and diversity of integrated LTC implementation. PMID- 25120414 TI - Esophageal Perforation due to Transesophageal Echocardiogram: New Endoscopic Clip Treatment. AB - Esophageal perforation due to transesophageal echocardiogram (TEE) during cardiac surgery is rare. A 72-year-old female underwent TEE during an operation for aortic valve replacement. Further, the patient presented hematemesis. Gastroscopy revealed an esophageal bleeding ulcer. Endoscopic therapy was successful. Although a CT scan excluded perforation, the patient became febrile, and a second gastroscopy revealed a big perforation at the site of ulcer. The patient's clinical condition required endoscopic intervention with a new OTSC((r)) clip (Ovesco Endoscopy, Tubingen, Germany). The perforation was successfully sealed. The patient remained on intravenous antibiotics, proton pump inhibitors and parenteral nutrition for few days, followed by enteral feeding. She was discharged fully recovered 3 months later. We clearly demonstrate an effective, less invasive treatment of an esophageal perforation with a new endoscopic clip. PMID- 25120415 TI - Severe Colitis Associated with both Epstein-Barr Virus and Cytomegalovirus Reactivation in a Patient with Severe Aplastic Anemia. AB - Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are members of the herpesvirus family and common causes of viral infection in humans. CMV infection of the gastrointestinal tract occurs mainly in immunocompromised individuals, on the other hand EBV infection and reactivation involving the gastrointestinal tract is very rare. A 56-year-old man was diagnosed with severe aplastic anemia and treated with antithymocyte globulin (ATG) and cyclosporine (CSP). After 2 years of ATG/CSP therapy, he suddenly started passing bloody diarrhea and developed a high fever despite CSP treatment. Endoscopic features included severe edema and multiple superficial ulcers; the patient was initially diagnosed with severe colitis resembling inflammatory bowel disease (IBD). However, his symptoms did not resolve with steroid treatment. Immunohistochemical analysis of samples obtained from a second colonoscopy showed cells positive for CMV, and in situ hybridization revealed EBV-encoded small RNA-1-positive cells. Additionally, the patient's serum was positive for C7-HRP, and both blood and colon tissues were positive for EBV DNA, which was detected using PCR analysis. We finally diagnosed the patient with colitis associated with reactivation of both CMV and EBV. The patient remains diarrhea-free after 1.5 years with scheduled globulin treatment and after cessation of immunosuppressive drug therapy. To our knowledge, this is the first reported case of an immunodeficient patient with severe hemorrhagic colitis that was associated with reactivation of both EBV and CMV, and whose endoscopic findings mimicked IBD. PMID- 25120416 TI - Characterization of primary afferent spinal innervation of mouse uterus. AB - The primary afferent innervation of the uterus is incompletely understood. The aim of this study was to identify the location and characteristics of primary afferent neurons that innervate the uterine horn of mice and correlate the different morphological types of putative primary afferent nerve endings, immunoreactive to the sensory marker, calcitonin gene related peptide (CGRP). Using retrograde tracing, injection of 5-10 MUL of 1,1'-didodecyl-3,3,3,3' tetramethylindocarbocyanine perchlorate (DiI) into discrete single sites in each uterine horn revealed a biomodal distribution of sensory neurons in dorsal root ganglia (DRG) with peak labeling occurring between T13-L3 and a second smaller peak between L6-S1. The mean cross sectional area of labeled cells was 463 MUm(2) +/- s.e.m. A significantly greater proportion of labeled neurons consisted of small cell bodies (<300 MUm(2)) in the sacral spinal cord (S2) compared with peak labeling at the lumbar (L2) region. In both sections and whole mount preparations, immunohistochemical staining for CGRP revealed substantial innervation of the uterus by CGRP-positive nerve fibers located primarily at the border between the circular and longitudinal muscle layers (N = 4). The nerve endings were classified into three distinct types: "single," "branching," or "complex," that often aligned preferentially in either the circular or longitudinal axis of the smooth muscles. Complex endings were often associated with mesenteric vessels. We have identified that the cell bodies of primary afferent neurons innervating the mouse uterus lie primarily in DRG at L2 and S1 spinal levels. Also, the greatest density of CGRP immunoreactivity lies within the myometrium, with at least three different morphological types of nerve endings identified. These findings will facilitate further investigations into the mechanisms underlying sensory transduction in mouse uterus. PMID- 25120417 TI - Bidirectional control of a one-dimensional robotic actuator by operant conditioning of a single unit in rat motor cortex. AB - The design of efficient neuroprosthetic devices has become a major challenge for the long-term goal of restoring autonomy to motor-impaired patients. One approach for brain control of actuators consists in decoding the activity pattern obtained by simultaneously recording large neuronal ensembles in order to predict in real time the subject's intention, and move the prosthesis accordingly. An alternative way is to assign the output of one or a few neurons by operant conditioning to control the prosthesis with rules defined by the experimenter, and rely on the functional adaptation of these neurons during learning to reach the desired behavioral outcome. Here, several motor cortex neurons were recorded simultaneously in head-fixed awake rats and were conditioned, one at a time, to modulate their firing rate up and down in order to control the speed and direction of a one-dimensional actuator carrying a water bottle. The goal was to maintain the bottle in front of the rat's mouth, allowing it to drink. After learning, all conditioned neurons modulated their firing rate, effectively controlling the bottle position so that the drinking time was increased relative to chance. The mean firing rate averaged over all bottle trajectories depended non-linearly on position, so that the mouth position operated as an attractor. Some modifications of mean firing rate were observed in the surrounding neurons, but to a lesser extent. Notably, the conditioned neuron reacted faster and led to a better control than surrounding neurons, as calculated by using the activity of those neurons to generate simulated bottle trajectories. Our study demonstrates the feasibility, even in the rodent, of using a motor cortex neuron to control a prosthesis in real-time bidirectionally. The learning process includes modifications of the activity of neighboring cortical neurons, while the conditioned neuron selectively leads the activity patterns associated with the prosthesis control. PMID- 25120418 TI - Longitudinal changes in task-evoked brain responses in Parkinson's disease patients with and without mild cognitive impairment. AB - Cognitive deficits are common in Parkinson's disease. Previous cross-sectional research has demonstrated a link between cognitive impairments and fronto striatal dopaminergic dysmodulation. However, longitudinal studies that link disease progression with altered task-evoked brain activity are lacking. Therefore, our objective was to longitudinally evaluate working-memory related brain activity changes in Parkinson's disease patients with and without mild cognitive impairment (MCI). Patients were recruited within a longitudinal cohort study of incident patients with idiopathic parkinsonism. We longitudinally (at baseline examination and at 12-months follow-up) compared 28 patients with Parkinson's disease without MCI with 11 patients with Parkinson's disease and MCI. Functional MRI blood oxygen level dependent signal was measured during a verbal two-back working-memory task. Patients with MCI under-recruited bilateral medial prefrontal cortex at both time-points (main effect of group: p < 0.001, uncorrected). Critically, a significant group-by-time interaction effect (p < 0.001, uncorrected) was found in the right fusiform gyrus, indicating that working-memory related activity decreased for patients with Parkinson's disease and MCI between baseline and follow-up, while patients without MCI were stable across time-points. The functional connectivity between right fusiform gyrus and bilateral caudate nucleus was stronger for patients without MCI relative to patients with MCI. Our findings support the view that deficits in working-memory updating are related to persistent fronto-striatal under-recruitments in patients with early phase Parkinson's disease and MCI. The longitudinal evolution of MCI in Parkinson's disease translates into additional task-evoked posterior cortical changes. PMID- 25120419 TI - Origin and function of short-latency inputs to the neural substrates underlying the acoustic startle reflex. AB - The acoustic startle reflex (ASR) is a survival mechanism of alarm, which rapidly alerts the organism to a sudden loud auditory stimulus. In rats, the primary ASR circuit encompasses three serially connected structures: cochlear root neurons (CRNs), neurons in the caudal pontine reticular nucleus (PnC), and motoneurons in the medulla and spinal cord. It is well-established that both CRNs and PnC neurons receive short-latency auditory inputs to mediate the ASR. Here, we investigated the anatomical origin and functional role of these inputs using a multidisciplinary approach that combines morphological, electrophysiological and behavioral techniques. Anterograde tracer injections into the cochlea suggest that CRNs somata and dendrites receive inputs depending, respectively, on their basal or apical cochlear origin. Confocal colocalization experiments demonstrated that these cochlear inputs are immunopositive for the vesicular glutamate transporter 1 (VGLUT1). Using extracellular recordings in vivo followed by subsequent tracer injections, we investigated the response of PnC neurons after contra-, ipsi-, and bilateral acoustic stimulation and identified the source of their auditory afferents. Our results showed that the binaural firing rate of PnC neurons was higher than the monaural, exhibiting higher spike discharges with contralateral than ipsilateral acoustic stimulations. Our histological analysis confirmed the CRNs as the principal source of short-latency acoustic inputs, and indicated that other areas of the cochlear nucleus complex are not likely to innervate PnC. Behaviorally, we observed a strong reduction of ASR amplitude in monaural earplugged rats that corresponds with the binaural summation process shown in our electrophysiological findings. Our study contributes to understand better the role of neuronal mechanisms in auditory alerting behaviors and provides strong evidence that the CRNs-PnC pathway mediates fast neurotransmission and binaural summation of the ASR. PMID- 25120420 TI - Urinary oxytocin positively correlates with performance in facial visual search in unmarried males, without specific reaction to infant face. AB - The neuropeptide oxytocin plays a central role in prosocial and parental behavior in non-human mammals as well as humans. It has been suggested that oxytocin may affect visual processing of infant faces and emotional reaction to infants. Healthy male volunteers (N = 13) were tested for their ability to detect infant or adult faces among adult or infant faces (facial visual search task). Urine samples were collected from all participants before the study to measure the concentration of oxytocin. Urinary oxytocin positively correlated with performance in the facial visual search task. However, task performance and its correlation with oxytocin concentration did not differ between infant faces and adult faces. Our data suggests that endogenous oxytocin is related to facial visual cognition, but does not promote infant-specific responses in unmarried men who are not fathers. PMID- 25120421 TI - Removing ballistocardiogram (BCG) artifact from full-scalp EEG acquired inside the MR scanner with Orthogonal Matching Pursuit (OMP). AB - Ballistocardiogram (BCG) artifact remains a major challenge that renders electroencephalographic (EEG) signals hard to interpret in simultaneous EEG and functional MRI (fMRI) data acquisition. Here, we propose an integrated learning and inference approach that takes advantage of a commercial high-density EEG cap, to estimate the BCG contribution in noisy EEG recordings from inside the MR scanner. To estimate reliably the full-scalp BCG artifacts, a near-optimal subset (20 out of 256) of channels first was identified using a modified recording setup. In subsequent recordings inside the MR scanner, BCG-only signal from this subset of channels was used to generate continuous estimates of the full-scalp BCG artifacts via inference, from which the intended EEG signal was recovered. The reconstruction of the EEG was performed with both a direct subtraction and an optimization scheme. We evaluated the performance on both synthetic and real contaminated recordings, and compared it to the benchmark Optimal Basis Set (OBS) method. In the challenging non-event-related-potential (non-ERP) EEG studies, our reconstruction can yield more than fourteen-fold improvement in reducing the normalized RMS error of EEG signals, compared to OBS. PMID- 25120423 TI - Processing of spatial sounds in human auditory cortex during visual, discrimination and 2-back tasks. AB - Previous imaging studies on the brain mechanisms of spatial hearing have mainly focused on sounds varying in the horizontal plane. In this study, we compared activations in human auditory cortex (AC) and adjacent inferior parietal lobule (IPL) to sounds varying in horizontal location, distance, or space (i.e., different rooms). In order to investigate both stimulus-dependent and task dependent activations, these sounds were presented during visual discrimination, auditory discrimination, and auditory 2-back memory tasks. Consistent with previous studies, activations in AC were modulated by the auditory tasks. During both auditory and visual tasks, activations in AC were stronger to sounds varying in horizontal location than along other feature dimensions. However, in IPL, this enhancement was detected only during auditory tasks. Based on these results, we argue that IPL is not primarily involved in stimulus-level spatial analysis but that it may represent such information for more general processing when relevant to an active auditory task. PMID- 25120422 TI - A review on auditory space adaptations to altered head-related cues. AB - In this article we present a review of current literature on adaptations to altered head-related auditory localization cues. Localization cues can be altered through ear blocks, ear molds, electronic hearing devices, and altered head related transfer functions (HRTFs). Three main methods have been used to induce auditory space adaptation: sound exposure, training with feedback, and explicit training. Adaptations induced by training, rather than exposure, are consistently faster. Studies on localization with altered head-related cues have reported poor initial localization, but improved accuracy and discriminability with training. Also, studies that displaced the auditory space by altering cue values reported adaptations in perceived source position to compensate for such displacements. Auditory space adaptations can last for a few months even without further contact with the learned cues. In most studies, localization with the subject's own unaltered cues remained intact despite the adaptation to a second set of cues. Generalization is observed from trained to untrained sound source positions, but there is mixed evidence regarding cross-frequency generalization. Multiple brain areas might be involved in auditory space adaptation processes, but the auditory cortex (AC) may play a critical role. Auditory space plasticity may involve context-dependent cue reweighting. PMID- 25120424 TI - Automatic real-time monitoring and assessment of tremor parameters in the upper limb from orientation data. AB - Upper limb tremor is the most prevalent movement disorder and, unfortunately, it is not effectively managed in a large proportion of the patients. Neuroprostheses that stimulate the sensorimotor pathways are one of the most promising alternatives although they are still under development. To enrich the interpretation of data recorded during long-term tremor monitoring and to increase the intelligence of tremor suppression neuroprostheses we need to be aware of the context. Context awareness is a major challenge for neuroprostheses and would allow these devices to react more quickly and appropriately to the changing demands of the user and/or task. Traditionally kinematic features are used to extract context information, with most recently the use of joint angles as highly potential features. In this paper we present two algorithms that enable the robust extraction of joint angle and related features to enable long-term continuous monitoring of tremor with context awareness. First, we describe a novel relative sensor placement identification technique based on orientation data. We focus on relative rather than absolute sensor location, because in many medical applications magnetic and inertial measurement units (MIMU) are used in a chain stretching over adjacent segments, or are always placed on a fixed set of locations. Subsequently we demonstrate how tremor parameters can be extracted from orientation data using an adaptive estimation algorithm. Relative sensor location was detected with an accuracy of 94.12% for the 4 MIMU configuration, and 100% for the 3 MIMU configurations. Kinematic tracking error values with an average deviation of 8% demonstrate our ability to estimate tremor from orientation data. The methods presented in this study constitute an important step toward more user-friendly and context-aware neuroprostheses for tremor suppression and monitoring. PMID- 25120425 TI - A new paradigm to induce mental stress: the Sing-a-Song Stress Test (SSST). AB - We here introduce a new experimental paradigm to induce mental stress in a quick and easy way while adhering to ethical standards and controlling for potential confounds resulting from sensory input and body movements. In our Sing-a-Song Stress Test, participants are presented with neutral messages on a screen, interleaved with 1-min time intervals. The final message is that the participant should sing a song aloud after the interval has elapsed. Participants sit still during the whole procedure. We found that heart rate and skin conductance during the 1-min intervals following the sing-a-song stress message are substantially higher than during intervals following neutral messages. The order of magnitude of the rise is comparable to that achieved by the Trier Social Stress Test. Skin conductance increase correlates positively with experienced stress level as reported by participants. We also simulated stress detection in real time. When using both skin conductance and heart rate, stress is detected for 18 out of 20 participants, approximately 10 s after onset of the sing-a-song message. In conclusion, the Sing-a-Song Stress Test provides a quick, easy, controlled and potent way to induce mental stress and could be helpful in studies ranging from examining physiological effects of mental stress to evaluating interventions to reduce stress. PMID- 25120427 TI - Investigating the effect of modifying the EEG cap lead configuration on the gradient artifact in simultaneous EEG-fMRI. AB - EEG data recorded during simultaneous fMRI are contaminated by large voltages generated by time-varying magnetic field gradients. Correction of the resulting gradient artifact (GA) generally involves low-pass filtering to attenuate the high-frequency voltage fluctuations of the GA, followed by subtraction of a GA template produced by averaging over repeats of the artifact waveforms. This average artifact subtraction (AAS) process relies on the EEG amplifier having a large enough dynamic range to characterize the artifact voltages and on invariance of the artifact waveform over repeated image acquisitions. Saturation of the amplifiers and changes in subject position can leave unwanted residual GA after AAS. Previous modeling work suggested that modifying the lead layout and the exit position of the cable bundle on the EEG cap could reduce the GA amplitude. Here, we used simulations and experiments to evaluate the effect of modifying the lead paths on the magnitude of the GA and on the residual artifact after AAS. The modeling work showed that for wire paths following great circles, the smallest overall GA occurs when the leads converge at electrode Cz. The performance of this new cap design was compared with a standard cap in experiments on a spherical agar phantom and human subjects. Using gradient pulses applied separately along the three Cartesian axes, we found that the GA due to the foot-head gradient was most significantly reduced relative to a standard cap for the phantom, whereas the anterior-posterior GA was most attenuated for human subjects. In addition, there was an overall 37% reduction in the RMS GA amplitude produced by a standard EPI sequence when comparing the two caps on the phantom. In contrast, the subjects showed an 11% increase in the average RMS of the GA. This work shows that the optimal design reduces the GA on a spherical phantom however; these gains are not translated to human subjects, probably due to the differences in geometry. PMID- 25120428 TI - Regulation and targeting of enzymes mediating Parkinson's disease pathogenesis: focus on Parkinson's disease kinases, GTPases, and ATPases. PMID- 25120426 TI - An anatomical and functional topography of human auditory cortical areas. AB - While advances in magnetic resonance imaging (MRI) throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla). Importantly, we illustrate that-whereas a group-based approach to analyze functional (tonotopic) maps is appropriate to highlight the main tonotopic axis the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e., myelination) as well as of functional properties (e.g., broadness of frequency tuning) is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post-mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions. PMID- 25120429 TI - Spike generation estimated from stationary spike trains in a variety of neurons in vivo. AB - To any model of brain function, the variability of neuronal spike firing is a problem that needs to be taken into account. Whereas the synaptic integration can be described in terms of the original Hodgkin-Huxley (H-H) formulations of conductance-based electrical signaling, the transformation of the resulting membrane potential into patterns of spike output is subjected to stochasticity that may not be captured with standard single neuron H-H models. The dynamics of the spike output is dependent on the normal background synaptic noise present in vivo, but the neuronal spike firing variability in vivo is not well studied. In the present study, we made long-term whole cell patch clamp recordings of stationary spike firing states across a range of membrane potentials from a variety of subcortical neurons in the non-anesthetized, decerebrated state in vivo. Based on the data, we formulated a simple, phenomenological model of the properties of the spike generation in each neuron that accurately captured the stationary spike firing statistics across all membrane potentials. The model consists of a parametric relationship between the mean and standard deviation of the inter-spike intervals, where the parameter is linearly related to the injected current over the membrane. This enabled it to generate accurate approximations of spike firing also under inhomogeneous conditions with input that varies over time. The parameters describing the spike firing statistics for different neuron types overlapped extensively, suggesting that the spike generation had similar properties across neurons. PMID- 25120432 TI - Stem cells for neonatal stroke- the future is here. PMID- 25120430 TI - How big is the myelinating orchestra? Cellular diversity within the oligodendrocyte lineage: facts and hypotheses. AB - Since monumental studies from scientists like His, Ramon y Cajal, Lorente de No and many others have put down roots for modern neuroscience, the scientific community has spent a considerable amount of time, and money, investigating any possible aspect of the evolution, development and function of neurons. Today, the complexity and diversity of myriads of neuronal populations, and their progenitors, is still focus of extensive studies in hundreds of laboratories around the world. However, our prevalent neuron-centric perspective has dampened the efforts in understanding glial cells, even though their active participation in the brain physiology and pathophysiology has been increasingly recognized over the years. Among all glial cells of the central nervous system (CNS), oligodendrocytes (OLs) are a particularly specialized type of cells that provide fundamental support to neuronal activity by producing the myelin sheath. Despite their functional relevance, the developmental mechanisms regulating the generation of OLs are still poorly understood. In particular, it is still not known whether these cells share the same degree of heterogeneity of their neuronal companions and whether multiple subtypes exist within the lineage. Here, we will review and discuss current knowledge about OL development and function in the brain and spinal cord. We will try to address some specific questions: do multiple OL subtypes exist in the CNS? What is the evidence for their existence and those against them? What are the functional features that define an oligodendrocyte? We will end our journey by reviewing recent advances in human pluripotent stem cell differentiation towards OLs. This exciting field is still at its earliest days, but it is quickly evolving with improved protocols to generate functional OLs from different spatial origins. As stem cells constitute now an unprecedented source of human OLs, we believe that they will become an increasingly valuable tool for deciphering the complexity of human OL identity. PMID- 25120431 TI - Striatal cholinergic interneurons in isolated generalized dystonia-rationale and perspectives for stem cell-derived cellular models. AB - Interneurons comprise a minority of the striatal neuronal population of roughly 5%. However, this heterogeneous population is of particular interest as it fulfills an important relay function in modulating the output of the only type of striatal projection neurons, i.e., the medium spiny neuron (MSN).One subtype of this heterogenous group, the cholinergic interneuron, is of particular scientific interest as there is a relevant body of evidence from animal models supporting its special significance in the disease process. The development of protocols for directed differentiation of human pluripotent stem cells (PSC) into striatal interneurons provides a unique opportunity to derive in vitro those cell types that are most severely affected in dystonia.In this review we first aim to give a concise overview about the normal function of striatal interneurons and their dysfunction in dystonia in order to identify the most relevant interneuronal subtype for the pathogenesis of dystonia. Secondly we demonstrate how knowledge about the embryonic development of striatal interneurons is of particular help for the development of differentiation protocols from PSC and by this depict potential ways of deriving in vitro disease models of dystonia. We furthermore address the question as to whether cell replacement therapies might represent a beneficial approach for the treatment of dystonia. PMID- 25120433 TI - Emerging role of the KCNT1 Slack channel in intellectual disability. AB - The sodium-activated potassium KNa channels Slack and Slick are encoded by KCNT1 and KCNT2, respectively. These channels are found in neurons throughout the brain, and are responsible for a delayed outward current termed I KNa. These currents integrate into shaping neuronal excitability, as well as adaptation in response to maintained stimulation. Abnormal Slack channel activity may play a role in Fragile X syndrome, the most common cause for intellectual disability and inherited autism. Slack channels interact directly with the fragile X mental retardation protein (FMRP) and I KNa is reduced in animal models of Fragile X syndrome that lack FMRP. Human Slack mutations that alter channel activity can also lead to intellectual disability, as has been found for several childhood epileptic disorders. Ongoing research is elucidating the relationship between mutant Slack channel activity, development of early onset epilepsies and intellectual impairment. This review describes the emerging role of Slack channels in intellectual disability, coupled with an overview of the physiological role of neuronal I KNa currents. PMID- 25120435 TI - Gain control mechanisms in spinal motoneurons. AB - Motoneurons provide the only conduit for motor commands to reach muscles. For many years, motoneurons were in fact considered to be little more than passive "wires". Systematic studies in the past 25 years however have clearly demonstrated that the intrinsic electrical properties of motoneurons are under strong neuromodulatory control via multiple sources. The discovery of potent neuromodulation from the brainstem and its ability to change the gain of motoneurons shows that the "passive" view of the motor output stage is no longer tenable. A mechanism for gain control at the motor output stage makes good functional sense considering our capability of generating an enormous range of forces, from very delicate (e.g., putting in a contact lens) to highly forceful (emergency reactions). Just as sensory systems need gain control to deal with a wide dynamic range of inputs, so to might motor output need gain control to deal with the wide dynamic range of the normal movement repertoire. Two problems emerge from the potential use of the brainstem monoaminergic projection to motoneurons for gain control. First, the projection is highly diffuse anatomically, so that independent control of the gains of different motor pools is not feasible. In fact, the system is so diffuse that gain for all the motor pools in a limb likely increases in concert. Second, if there is a system that increases gain, probably a system to reduce gain is also needed. In this review, we summarize recent studies that show local inhibitory circuits within the spinal cord, especially reciprocal and recurrent inhibition, have the potential to solve both of these problems as well as constitute another source of gain modulation. PMID- 25120436 TI - Inhibitory projections from the ventral nucleus of the trapezoid body to the medial nucleus of the trapezoid body in the mouse. AB - Neurons in the medial nucleus of the trapezoid body (MNTB) receive prominent excitatory input through the calyx of Held, a giant synapse that produces large and fast excitatory currents. MNTB neurons also receive inhibitory glycinergic inputs that are also large and fast, and match the calyceal excitation in terms of synaptic strength. GABAergic inputs provide additional inhibition to MNTB neurons. Inhibitory inputs to MNTB modify spiking of MNTB neurons both in-vitro and in-vivo, underscoring their importance. Surprisingly, the origin of the inhibitory inputs to MNTB has not been shown conclusively. We performed retrograde tracing, anterograde tracing, immunohistochemical experiments, and electrophysiological recordings to address this question. The results support the ventral nucleus of the trapezoid body (VNTB) as at least one major source of glycinergic input to MNTB. VNTB fibers enter the ipsilateral MNTB, travel along MNTB principal neurons and produce several bouton-like presynaptic terminals. Further, the contribution of GABA to the total inhibition declines during development, resulting in only a very minor fraction of GABAergic inhibition in adulthood, which is matched in time by a reduction in expression of a GABA synthetic enzyme in VNTB principal neurons. PMID- 25120434 TI - A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress. AB - Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded-protein response (UPR) through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS). Toxic accumulation of ROS within ER and mitochondria disturbs fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways have been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease, and others. In this review, we have discussed the UPR signaling pathways, and networking between ER stress-induced inflammatory pathways, oxidative stress, and mitochondrial signaling events, which further induce or exacerbate ER stress. PMID- 25120439 TI - Plasma membrane transporters GAT-1 and GAT-3 contribute to heterogeneity of GABAergic synapses in neocortex. AB - Cortical GABAergic synapses exhibit a high degree of molecular, anatomical and functional heterogeneity of their neurons of origins, presynaptic mechanisms, receptors, and scaffolding proteins. GABA transporters (GATs) have an important role in regulating GABA levels; among them, GAT-1 and GAT-3 play a prominent role in modulating tonic and phasic GABAAR-mediated inhibition. We asked whether GAT-1 and GAT-3 contribute to generating heterogeneity by studying their ultrastructural localization at cortical symmetric synapses using pre- and post embedding electron microcopy. GAT-1 and GAT-3 staining at symmetric synapses showed that in some cases the transporters were localized exclusively over axon terminals; in others they were in both axon terminals and perisynaptic astrocytic processes; and in some others GAT-1 and GAT-3 were in perisynaptic astrocytic processes only. Moreover, we showed that the organizational pattern of GAT-1, but not of GAT-3, exhibits a certain degree of specificity related to the post synaptic target of GABAergic synapses. These findings show that symmetric synapses expressing GAT-1 or GAT-3 are heterogeneous, and indicate that plasma membrane transporters can contribute to synaptic heterogeneity. PMID- 25120437 TI - Sound-by-sound thalamic stimulation modulates midbrain auditory excitability and relative binaural sensitivity in frogs. AB - Descending circuitry can modulate auditory processing, biasing sensitivity to particular stimulus parameters and locations. Using awake in vivo single unit recordings, this study tested whether electrical stimulation of the thalamus modulates auditory excitability and relative binaural sensitivity in neurons of the amphibian midbrain. In addition, by using electrical stimuli that were either longer than the acoustic stimuli (i.e., seconds) or presented on a sound-by-sound basis (ms), experiments addressed whether the form of modulation depended on the temporal structure of the electrical stimulus. Following long duration electrical stimulation (3-10 s of 20 Hz square pulses), excitability (spikes/acoustic stimulus) to free-field noise stimuli decreased by 32%, but returned over 600 s. In contrast, sound-by-sound electrical stimulation using a single 2 ms duration electrical pulse 25 ms before each noise stimulus caused faster and varied forms of modulation: modulation lasted <2 s and, in different cells, excitability either decreased, increased or shifted in latency. Within cells, the modulatory effect of sound-by-sound electrical stimulation varied between different acoustic stimuli, including for different male calls, suggesting modulation is specific to certain stimulus attributes. For binaural units, modulation depended on the ear of input, as sound-by-sound electrical stimulation preceding dichotic acoustic stimulation caused asymmetric modulatory effects: sensitivity shifted for sounds at only one ear, or by different relative amounts for both ears. This caused a change in the relative difference in binaural sensitivity. Thus, sound-by-sound electrical stimulation revealed fast and ear-specific (i.e., lateralized) auditory modulation that is potentially suited to shifts in auditory attention during sound segregation in the auditory scene. PMID- 25120440 TI - Differential processing of natural scenes in posterior cortical atrophy and in Alzheimer's disease, as measured with a saccade choice task. AB - Atrophy of the medial temporal lobe structures that support scene perception and the binding of an object to its context (i.e., the hippocampus and the parahippocampal cortex) appears early in the course of Alzheimer's disease (AD). However, few studies have investigated scene perception in people with AD. Here, we assessed the ability to find a target object within a natural scene in people with AD and in people with posterior cortical atrophy (PCA, a variant of AD). Pairs of color photographs were displayed on the left and right of a fixation cross for 1 s. In separate blocks of trials, participants were asked to categorize the target (an animal) by either moving their eyes toward the photograph containing the target (the saccadic choice task) or pressing a key corresponding to the target's location (the manual choice task). Isolated objects and objects within scenes were studied in both tasks. Participants with PCA were more impaired in detection of a target within a scene than participants with AD. The latter's performance pattern was more similar to that of age-matched controls in terms of accuracy, saccade latencies and the benefit gained from contextual information. Participants with PCA benefited less from contextual information in both the saccade and the manual choice tasks-suggesting that people with posterior brain lesions have impairments in figure/ground segregation and are more sensitive to object crowding. PMID- 25120438 TI - Activation of lateral hypothalamus-projecting parabrachial neurons by intraorally delivered gustatory stimuli. AB - The present study investigated a subpopulation of neurons in the mouse parabrachial nucleus (PbN), a gustatory and visceral relay area in the brainstem, that project to the lateral hypothalamus (LH). We made injections of the retrograde tracer Fluorogold (FG) into LH, resulting in fluorescent labeling of neurons located in different regions of the PbN. Mice were stimulated through an intraoral cannula with one of seven different taste stimuli, and PbN sections were processed for immunohistochemical detection of the immediate early gene c Fos, which labels activated neurons. LH projection neurons were found in all PbN subnuclei, but in greater concentration in lateral subnuclei, including the dorsal lateral subnucleus (dl). Fos-like immunoreactivity (FLI) was observed in the PbN in a stimulus-dependent pattern, with the greatest differentiation between intraoral stimulation with sweet (0.5 M sucrose) and bitter (0.003 M quinine) compounds. In particular, sweet and umami-tasting stimuli evoked robust FLI in cells in the dl, whereas quinine evoked almost no FLI in cells in this subnucleus. Double-labeled cells were also found in the greatest quantity in the dl. Overall, these results support the hypothesis that the dl contains direct a projection to the LH that is activated preferentially by appetitive compounds; this projection may be mediated by taste and/or postingestive mechanisms. PMID- 25120442 TI - Executive function and bilingualism in young and older adults. AB - Research suggests that being bilingual results in advantages on executive control processes and disadvantages on language tasks relative to monolinguals. Furthermore, the executive function advantage is thought to be larger in older than younger adults, suggesting that bilingualism may buffer against age-related changes in executive function. However, there are potential confounds in some of the previous research, as well as inconsistencies in the literature. The goal of the current investigation was to examine the presence of a bilingual advantage in executive control and a bilingual disadvantage on language tasks in the same sample of young and older monolingual anglophones, monolingual francophones, and French/English bilinguals. Participants completed a series of executive function tasks, including a Stroop task, a Simon task, a sustained attention to response task (SART), the Wisconsin Card Sort Test (WCST), and the digit span subtest of the Wechsler Adult Intelligence Scale, and language tasks, including the Boston Naming Test (BNT), and category and letter fluency. The results do not demonstrate an unequivocal advantage for bilinguals on executive function tasks and raise questions about the reliability, robustness and/or specificity of previous findings. The results also did not demonstrate a disadvantage for bilinguals on language tasks. Rather, they suggest that there may be an influence of the language environment. It is concluded that additional research is required to fully characterize any language group differences in both executive function and language tasks. PMID- 25120441 TI - Niche convergence suggests functionality of the nocturnal fovea. AB - The fovea is a declivity of the retinal surface associated with maximum visual acuity. Foveae are widespread across vertebrates, but among mammals they are restricted to haplorhine primates (tarsiers, monkeys, apes, and humans), which are primarily diurnal. Thus primates have long contributed to the view that foveae are functional adaptations to diurnality. The foveae of tarsiers, which are nocturnal, are widely interpreted as vestigial traits and therefore evidence of a diurnal ancestry. This enduring premise is central to adaptive hypotheses on the origins of anthropoid primates; however, the question of whether tarsier foveae are functionless anachronisms or nocturnal adaptations remains open. To explore this question, we compared the diets of tarsiers (Tarsius) and scops owls (Otus), taxa united by numerous anatomical homoplasies, including foveate vision. A functional interpretation of these homoplasies predicts dietary convergence. We tested this prediction by analyzing stable isotope ratios that integrate dietary information. In Borneo and the Philippines, the stable carbon isotope compositions of Tarsius and Otus were indistinguishable, whereas the stable nitrogen isotope composition of Otus was marginally higher than that of Tarsius. Our results indicate that species in both genera consumed mainly ground-dwelling prey. Taken together, our findings support a functional interpretation of the many homoplasies shared by tarsiers and scops owls, including a retinal fovea. We suggest that the fovea might function similarly in tarsiers and scops owls by calibrating the auditory localization pathway. The integration of auditory localization and visual fixation during prey detection and acquisition might be critical at low light levels. PMID- 25120443 TI - On the generalizability of resting-state fMRI machine learning classifiers. AB - Machine learning classifiers have become increasingly popular tools to generate single-subject inferences from fMRI data. With this transition from the traditional group level difference investigations to single-subject inference, the application of machine learning methods can be seen as a considerable step forward. Existing studies, however, have given scarce or no information on the generalizability to other subject samples, limiting the use of such published classifiers in other research projects. We conducted a simulation study using publicly available resting-state fMRI data from the 1000 Functional Connectomes and COBRE projects to examine the generalizability of classifiers based on regional homogeneity of resting-state time series. While classification accuracies of up to 0.8 (using sex as the target variable) could be achieved on test datasets drawn from the same study as the training dataset, the generalizability of classifiers to different study samples proved to be limited albeit above chance. This shows that on the one hand a certain amount of generalizability can robustly be expected, but on the other hand this generalizability should not be overestimated. Indeed, this study substantiates the need to include data from several sites in a study investigating machine learning classifiers with the aim of generalizability. PMID- 25120444 TI - Toward a new conception of habit and self-control in adolescent maturation. PMID- 25120446 TI - Assessment of size ordered recruitment. PMID- 25120445 TI - Roles of frontal and temporal regions in reinterpreting semantically ambiguous sentences. AB - Semantic ambiguity resolution is an essential and frequent part of speech comprehension because many words map onto multiple meanings (e.g., "bark," "bank"). Neuroimaging research highlights the importance of the left inferior frontal gyrus (LIFG) and the left posterior temporal cortex in this process but the roles they serve in ambiguity resolution are uncertain. One possibility is that both regions are engaged in the processes of semantic reinterpretation that follows incorrect interpretation of an ambiguous word. Here we used fMRI to investigate this hypothesis. 20 native British English monolinguals were scanned whilst listening to sentences that contained an ambiguous word. To induce semantic reinterpretation, the disambiguating information was presented after the ambiguous word and delayed until the end of the sentence (e.g., "the teacher explained that the BARK was going to be very damp"). These sentences were compared to well-matched unambiguous sentences. Supporting the reinterpretation hypothesis, these ambiguous sentences produced more activation in both the LIFG and the left posterior inferior temporal cortex. Importantly, all but one subject showed ambiguity-related peaks within both regions, demonstrating that the group level results were driven by high inter-subject consistency. Further support came from the finding that activation in both regions was modulated by meaning dominance. Specifically, sentences containing biased ambiguous words, which have one more dominant meaning, produced greater activation than those with balanced ambiguous words, which have two equally frequent meanings. Because the context always supported the less frequent meaning, the biased words require reinterpretation more often than balanced words. This is the first evidence of dominance effects in the spoken modality and provides strong support that frontal and temporal regions support the updating of semantic representations during speech comprehension. PMID- 25120448 TI - Habit and embodiment in Merleau-Ponty. PMID- 25120447 TI - The role of parietal cortex in the formation of color and motion based concepts. AB - Imaging evidence shows that separate subdivisions of parietal cortex, in and around the intraparietal sulcus (IPS), are engaged when stimuli are grouped according to color and to motion (Zeki and Stutters, 2013). Since grouping is an essential step in the formation of concepts, we wanted to learn whether parietal cortex is also engaged in the formation of concepts according to these two attributes. Using functional magnetic resonance imaging (fMRI), and choosing the recognition of concept-based color or motion stimuli as our paradigm, we found that there was strong concept-related activity in and around the IPS, a region whose homolog in the macaque monkey is known to receive direct but segregated anatomical inputs from V4 and V5. Parietal activity related to color concepts was juxtaposed but did not overlap with activity related to motion concepts, thus emphasizing the continuation of the segregation of color and motion into the conceptual system. Concurrent retinotopic mapping experiments showed that within the parietal cortex, concept-related activity increases within later stage IPS areas. PMID- 25120449 TI - Agency over a phantom limb and electromyographic activity on the stump depend on visuomotor synchrony: a case study. AB - Most patients, post-amputation, report the experience of a phantom limb. Some even sense voluntary movements when viewing a mirror image of the intact limb superimposed onto the phantom limb. While delayed visual feedback of an action is known to reduce a sense of agency, the effect of delayed visual feedback on phantom motor sensation (i.e., sense of controlling a phantom limb) has not been examined. Using a video-projection system, we examined the effect of delayed visual feedback on phantom motor sensation in an upper-limb amputee (male; left upper-limb amputation). He was instructed to view mirrored video images of his intact hand clasping and unclasping during a phantom limb movement. He then rated the intensity of the phantom motor sensation. Three types of hand movement images were presented as follows: synchronous, asynchronous with a 250-ms delay, and asynchronous with a 500-ms delay. Results showed that phantom motor sensation decreased when the image was delayed by 250 and 500 ms. However, when we instructed the patient to adjust the phase of phantom limb movement to that of the image with a 500-ms delay, phantom motor sensation increased. There was also a positive correlation between intensity of phantom motor sensation and electromyographic (EMG) activity on deltoids at the patient's stump. These results suggest that phantom motor sensation and EMG activity on the stump depend on visuomotor synchrony and top-down effects. PMID- 25120450 TI - Neurofeminism and feminist neurosciences: a critical review of contemporary brain research. AB - To date, feminist approaches to neurosciences have evaluated the debates surrounding practices of knowledge production within and research results of contemporary brain research. Consequently, neurofeminist scholars have critically examined gendered impacts of neuroscientific research. Feminist neuroscientists also develop research approaches for a more gender-appropriate neuroscientific research on several levels. Based on neurofeminist critique feminist neuroscientists aim to enrich neuroscientific work by offering methodological suggestions for a more differentiated setup of categories and experimental designs, for reflective result presentations and interpretations as well as for the analysis of result validity. Reframing neuro-epistemologies by including plasticity concepts works to uncover social influences on the gendered development of the brain and of behavior. More recently, critical work on contemporary neurocultures has highlighted the entanglements of neuroscientific research within society and the implications of 'neurofacts' for gendered cultural symbolisms, social practices, and power relations. Not least, neurofeminism critically analyses the portrayal of neuro-knowledge in popular media. This article presents on overview on neurofeminist debates and on current approaches of feminist neurosciences. The authors conclude their review by calling for a more gender-appropriate research approach that takes into account both its situatedness and reflections on the neuroscientific agenda, but also questions neurofeminist discourse in regards to uses and misuses of its concepts. PMID- 25120451 TI - Situated affective and social neuroscience. PMID- 25120452 TI - Marking the counterfactual: ERP evidence for pragmatic processing of German subjunctives. AB - Counterfactual conditionals are frequently used in language to express potentially valid reasoning from factually false suppositions. Counterfactuals provide two pieces of information: their literal meaning expresses a suppositional dependency between an antecedent (If the dice had been rigged...) and a consequent (... then the game would have been unfair). Their second, backgrounded meaning refers to the opposite state of affairs and suggests that, in fact, the dice were not rigged and the game was fair. Counterfactual antecedents are particularly intriguing because they set up a counterfactual world which is known to be false, but which is nevertheless kept to when evaluating the conditional's consequent. In the last years several event-related potential (ERP) studies have targeted the processing of counterfactual consequents, yet counterfactual antecedents have remained unstudied. We present an EEG/ERP investigation which employed German conditionals to compare subjunctive mood (which marks counterfactuality) with indicative mood at the critical point of mood disambiguation via auxiliary introduction in the conditional's antecedent. Conditional sentences were presented visually one word at a time. Participants completed an acceptability judgment and probe detection task which was not related to the critical manipulation of linguistic mood. ERPs at the point of mood disambiguation in the antecedent were compared between indicative and subjunctive. Our main finding is a transient negative deflection in frontal regions for subjunctive compared to indicative mood in a time-window of 450-600 ms. We discuss this novel finding in respect to working memory requirements for rule application and increased referential processing demands for the representation of counterfactuals' dual meaning. Our result suggests that the counterfactually implied dual meaning is processed without any delay at the earliest point where counterfactuality is marked by subjunctive mood. PMID- 25120453 TI - Magnetoencephalographic study on facial movements. AB - In this review, we introduced our three studies that focused on facial movements. In the first study, we examined the temporal characteristics of neural responses elicited by viewing mouth movements, and assessed differences between the responses to mouth opening and closing movements and an averting eyes condition. Our results showed that the occipitotemporal area, the human MT/V5 homologue, was active in the perception of both mouth and eye motions. Viewing mouth and eye movements did not elicit significantly different activity in the occipitotemporal area, which indicated that perception of the movement of facial parts may be processed in the same manner, and this is different from motion in general. In the second study, we investigated whether early activity in the occipitotemporal region evoked by eye movements was influenced by the facial contour and/or features such as the mouth. Our results revealed specific information processing for eye movements in the occipitotemporal region, and this activity was significantly influenced by whether movements appeared with the facial contour and/or features, in other words, whether the eyes moved, even if the movement itself was the same. In the third study, we examined the effects of inverting the facial contour (hair and chin) and features (eyes, nose, and mouth) on processing for static and dynamic face perception. Our results showed the following: (1) In static face perception, activity in the right fusiform area was affected more by the inversion of features while that in the left fusiform area was affected more by a disruption in the spatial relationship between the contour and features; and (2) In dynamic face perception, activity in the right occipitotemporal area was affected by the inversion of the facial contour. PMID- 25120454 TI - Uni- and crossmodal refractory period effects of event-related potentials provide insights into the development of multisensory processing. AB - To assess uni- and multisensory development in humans, uni- and crossmodal event related potential (ERP) refractory period effects were investigated. Forty-one children from 4 to 12 years of age and 15 young adults performed a bimodal oddball task with frequent and rare visual and auditory stimuli presented with two different interstimulus intervals (ISIs). Amplitudes of the visual and auditory ERPs were modulated as a function of the age of the participants, the modality of the preceding stimulus (same vs. different) and the preceding ISI (1000 or 2000 ms). While unimodal refractory period effects were observed in all age groups, crossmodal refractory period effects differed among age groups. Early crossmodal interactions (<150 ms) existing in the youngest age group (4-6 years) disappeared, while later crossmodal interactions (>150 ms) emerged with a parietal topography in older children and adults. Our results are compatible with the intersensory differentiation and the multisensory perceptual narrowing approach of multisensory development. Moreover, our data suggest that uni- and multisensory development run in parallel with unimodal development leading. PMID- 25120455 TI - Unconvincing support for role of mirror neurons in "action understanding": commentary on Michael et al. (2014). PMID- 25120456 TI - It's too quick to blame myself-the effects of fast and slow rates of change on credit assignment during object lifting. AB - Although there have been substantial research efforts examining the effect of various rates of change in reaching movements, there has been little to no research devoted to this issue during object manipulation tasks. In force-field and visuomotor adaptation studies, two parallel processes have been identified: first, a fast process that adapts and de-adapts quickly is thought to enable the actor to deal with potentially transient perturbations. Second, a slower, but longer lasting process adapts if these initial perturbations persist over time. In a largely separate body of research, the role of credit assignment has been examined in terms of allotting the cause of errors to changes in the body vs. changes in the outside world. Of course, these two processes are usually linked within the real world, with short lasting perturbations most often being linked to external causes and longer lasting perturbations being linked to internal causes. Here, we demonstrate that the increases in load forces associated with a gradual increase in object weight during a natural object lifting task are transferred when lifting a novel object, whereas a sudden increase in object weight is not. We speculate that gradual rates of change in the weight of the object being lifted are attributed to the self, whereas fast rates of change are more likely to be attributed to the external environment. This study extends our knowledge of the multiple timescales involved in motor learning to a more natural object manipulation scenario, while concurrently providing support for the hypothesis that the multiple time scales involved in motor learning are tuned for different learning contexts. PMID- 25120457 TI - The feedback related negativity encodes both social rejection and explicit social expectancy violation. AB - Humans consistently make predictions about the valence of future events and use feedback to validate initial predictions. While the valence of outcomes provides utilitarian information, the accuracy of predictions is crucial for future performance adjustment. The feedback related negativity (FRN), identified as a marker of reward prediction error, possibly encodes social rejection and social prediction error. To test this possibility, we used event related potential (ERP) techniques combined with social tasks in which participants were required to make explicit predictions (whether others will accept their "friend request" or not, Experiment 1) or implicit predictions (whether they would like this person or not, Experiment 2) respectively, and then received social feedback. We found that the FRN is sensitive to social rejection and explicit social prediction error in Experiment 1 but not implicit social prediction error in Experiment 2. We conclude that the FRN encodes social rejection and explicit social expectancy violation. PMID- 25120458 TI - Intraindividual reaction time variability affects P300 amplitude rather than latency. AB - The neural correlates of intraindividual response variability were investigated in a serial choice reaction time (CRT) task. Reaction times (RTs) from the faster and slower portions of the RT distribution for the task were separately aggregated and associated P300 event-related potentials computed. Independent behavioral measures of executive function and IQ were also recorded. Across frontal, fronto-central, central, centro-parietal and parietal scalp regions, P300 amplitudes were significantly greater for faster relative to slower behavioral responses. However, P300 peak amplitude latencies did not differ according to the speed of the behavioral RT. Importantly, controlling for select independent measures of executive function attenuated shared variance in P300 amplitude for faster and slower trials. The findings suggest that P300 amplitude rather than latency is associated with the speed of behavioral RTs, and the possibility that fluctuations in executive control underlie variability in speeded responding. PMID- 25120459 TI - Does co-morbid obsessive-compulsive disorder modify the abnormal language processing in schizophrenia patients? An FMRI study. AB - BACKGROUND: Impaired language processing is one of the most replicated findings in functional brain studies of schizophrenia (SCH). This is demonstrated by reduced activations in left prefrontal language areas (i.e., BA44/45, the inferior frontal gyrus, IFG) presented as decreased language lateralization. This finding was documented both in chronic as well as in first-episode SCH patients, arguing for a neurobiological marker for SCH. In a previous study, we demonstrated the specificity of this finding to SCH patients when compared to obsessive-compulsive disorder (OCD) patients in whom language processing was similar to healthy controls. Since a sizable proportion of SCH patients also meet DSM-IV criteria for OCD, we further sought to elucidate whether OCD attenuates abnormal prefrontal language lateralization in this unique group of schizo obsessive patients compared to their non-OCD-SCH counterparts. METHODS: We used functional magnetic resonance imaging (fMRI) to investigate regional activation and language lateralization in the left and right IFG and inter-hemispheric functional connectivity (FC) during a language task of auditory verb generation in 14 SCH patients with OCD, compared to 17 SCH patients without OCD, 13 OCD patients and 14 healthy controls. RESULTS: No between-group differences were found in the behavioral measurements of word generation. However, while OCD patients were indistinguishable from healthy volunteers, a similarly reduced lateralization in the IFG and diminished inter-hemispheric FC was noted in the two SCH groups with and without OCD. CONCLUSION: The co-occurrence of OCD in SCH does not attenuate abnormal processing of language as reflected by regional IFG activity and FC. These results further support the notion that these language processing abnormalities are characteristic of SCH and that SCH-OCD combined psychopathology is more akin to SCH than to OCD. PMID- 25120460 TI - Masking reveals parallel form systems in the visual brain. AB - It is generally supposed that there is a single, hierarchically organized pathway dedicated to form processing, in which complex forms are elaborated from simpler ones, beginning with the orientation-selective cells of V1. In this psychophysical study, we undertook to test another hypothesis, namely that the brain's visual form system consists of multiple parallel systems and that complex forms are other than the sum of their parts. Inspired by imaging experiments which show that forms of increasing perceptual complexity (lines, angles, and rhombuses) constituted from the same elements (lines) activate the same visual areas (V1, V2, and V3) with the same intensity and latency (Shigihara and Zeki, 2013, 2014), we used backward masking to test the supposition that these forms are processed in parallel. We presented subjects with lines, angles, and rhombuses as different target-mask pairs. Evidence in favor of our supposition would be if masking is the most effective when target and mask are processed by the same system and least effective when they are processed in different systems. Our results showed that rhombuses were strongly masked by rhombuses but only weakly masked by lines or angles, but angles and lines were well masked by each other. The relative resistance of rhombuses to masking by low-level forms like lines and angles suggests that complex forms like rhombuses may be processed in a separate parallel system, whereas lines and angles are processed in the same one. PMID- 25120461 TI - Structure of receptive fields in a computational model of area 3b of primary sensory cortex. AB - In a previous work, we introduced a computational model of area 3b which is built upon the neural field theory and receives input from a simplified model of the index distal finger pad populated by a random set of touch receptors (Merkell cells). This model has been shown to be able to self-organize following the random stimulation of the finger pad model and to cope, to some extent, with cortical or skin lesions. The main hypothesis of the model is that learning of skin representations occurs at the thalamo-cortical level while cortico-cortical connections serve a stereotyped competition mechanism that shapes the receptive fields. To further assess this hypothesis and the validity of the model, we reproduced in this article the exact experimental protocol of DiCarlo et al. that has been used to examine the structure of receptive fields in area 3b of the primary somatosensory cortex. Using the same analysis toolset, the model yields consistent results, having most of the receptive fields to contain a single region of excitation and one to several regions of inhibition. We further proceeded our study using a dynamic competition that deeply influences the formation of the receptive fields. We hypothesized this dynamic competition to correspond to some form of somatosensory attention that may help to precisely shape the receptive fields. To test this hypothesis, we designed a protocol where an arbitrary region of interest is delineated on the index distal finger pad and we either (1) instructed explicitly the model to attend to this region (simulating an attentional signal) (2) preferentially trained the model on this region or (3) combined the two aforementioned protocols simultaneously. Results tend to confirm that dynamic competition leads to shrunken receptive fields and its joint interaction with intensive training promotes a massive receptive fields migration and shrinkage. PMID- 25120462 TI - Associative learning of classical conditioning as an emergent property of spatially extended spiking neural circuits with synaptic plasticity. AB - Associative learning of temporally disparate events is of fundamental importance for perceptual and cognitive functions. Previous studies of the neural mechanisms of such association have been mainly focused on individual neurons or synapses, often with an assumption that there is persistent neural firing activity that decays slowly. However, experimental evidence supporting such firing activity for associative learning is still inconclusive. Here we present a novel, alternative account of associative learning in the context of classical conditioning, demonstrating that it is an emergent property of a spatially extended, spiking neural circuit with spike-timing dependent plasticity and short term synaptic depression. We show that both the conditioned and unconditioned stimuli can be represented by spike sequences which are produced by wave patterns propagating through the network, and that the interactions of these sequences are timing dependent. After training, the occurrence of the sequence encoding the conditioned stimulus (CS) naturally regenerates that encoding the unconditioned stimulus (US), therefore resulting in association between them. Such associative learning based on interactions of spike sequences can happen even when the timescale of their separation is significantly larger than that of individual neurons. In particular, our network model is able to account for the temporal contiguity property of classical conditioning, as observed in behavioral studies. We further show that this emergent associative learning in our network model is quite robust to noise perturbations. Our results therefore demonstrate that associative learning of temporally disparate events can happen in a distributed way at the level of neural circuits. PMID- 25120463 TI - 1D-3D hybrid modeling-from multi-compartment models to full resolution models in space and time. AB - Investigation of cellular and network dynamics in the brain by means of modeling and simulation has evolved into a highly interdisciplinary field, that uses sophisticated modeling and simulation approaches to understand distinct areas of brain function. Depending on the underlying complexity, these models vary in their level of detail, in order to cope with the attached computational cost. Hence for large network simulations, single neurons are typically reduced to time dependent signal processors, dismissing the spatial aspect of each cell. For single cell or networks with relatively small numbers of neurons, general purpose simulators allow for space and time-dependent simulations of electrical signal processing, based on the cable equation theory. An emerging field in Computational Neuroscience encompasses a new level of detail by incorporating the full three-dimensional morphology of cells and organelles into three-dimensional, space and time-dependent, simulations. While every approach has its advantages and limitations, such as computational cost, integrated and methods-spanning simulation approaches, depending on the network size could establish new ways to investigate the brain. In this paper we present a hybrid simulation approach, that makes use of reduced 1D-models using e.g., the NEURON simulator-which couples to fully resolved models for simulating cellular and sub-cellular dynamics, including the detailed three-dimensional morphology of neurons and organelles. In order to couple 1D- and 3D-simulations, we present a geometry-, membrane potential- and intracellular concentration mapping framework, with which graph- based morphologies, e.g., in the swc- or hoc-format, are mapped to full surface and volume representations of the neuron and computational data from 1D simulations can be used as boundary conditions for full 3D simulations and vice versa. Thus, established models and data, based on general purpose 1D-simulators, can be directly coupled to the emerging field of fully resolved, highly detailed 3D-modeling approaches. We present the developed general framework for 1D/3D hybrid modeling and apply it to investigate electrically active neurons and their intracellular spatio-temporal calcium dynamics. PMID- 25120464 TI - Operant conditioning: a minimal components requirement in artificial spiking neurons designed for bio-inspired robot's controller. AB - In this paper, we investigate the operant conditioning (OC) learning process within a bio-inspired paradigm, using artificial spiking neural networks (ASNN) to act as robot brain controllers. In biological agents, OC results in behavioral changes learned from the consequences of previous actions, based on progressive prediction adjustment from rewarding or punishing signals. In a neurorobotics context, virtual and physical autonomous robots may benefit from a similar learning skill when facing unknown and unsupervised environments. In this work, we demonstrate that a simple invariant micro-circuit can sustain OC in multiple learning scenarios. The motivation for this new OC implementation model stems from the relatively complex alternatives that have been described in the computational literature and recent advances in neurobiology. Our elementary kernel includes only a few crucial neurons, synaptic links and originally from the integration of habituation and spike-timing dependent plasticity as learning rules. Using several tasks of incremental complexity, our results show that a minimal neural component set is sufficient to realize many OC procedures. Hence, with the proposed OC module, designing learning tasks with an ASNN and a bio inspired robot context leads to simpler neural architectures for achieving complex behaviors. PMID- 25120465 TI - Brain-computer interface-based robotic end effector system for wrist and hand rehabilitation: results of a three-armed randomized controlled trial for chronic stroke. AB - The objective of this study was to investigate the efficacy of an Electroencephalography (EEG)-based Motor Imagery (MI) Brain-Computer Interface (BCI) coupled with a Haptic Knob (HK) robot for arm rehabilitation in stroke patients. In this three-arm, single-blind, randomized controlled trial; 21 chronic hemiplegic stroke patients (Fugl-Meyer Motor Assessment (FMMA) score 10 50), recruited after pre-screening for MI BCI ability, were randomly allocated to BCI-HK, HK or Standard Arm Therapy (SAT) groups. All groups received 18 sessions of intervention over 6 weeks, 3 sessions per week, 90 min per session. The BCI-HK group received 1 h of BCI coupled with HK intervention, and the HK group received 1 h of HK intervention per session. Both BCI-HK and HK groups received 120 trials of robot-assisted hand grasping and knob manipulation followed by 30 min of therapist-assisted arm mobilization. The SAT group received 1.5 h of therapist assisted arm mobilization and forearm pronation-supination movements incorporating wrist control and grasp-release functions. In all, 14 males, 7 females, mean age 54.2 years, mean stroke duration 385.1 days, with baseline FMMA score 27.0 were recruited. The primary outcome measure was upper extremity FMMA scores measured mid-intervention at week 3, end-intervention at week 6, and follow-up at weeks 12 and 24. Seven, 8 and 7 subjects underwent BCI-HK, HK and SAT interventions respectively. FMMA score improved in all groups, but no intergroup differences were found at any time points. Significantly larger motor gains were observed in the BCI-HK group compared to the SAT group at weeks 3, 12, and 24, but motor gains in the HK group did not differ from the SAT group at any time point. In conclusion, BCI-HK is effective, safe, and may have the potential for enhancing motor recovery in chronic stroke when combined with therapist assisted arm mobilization. PMID- 25120467 TI - Sequential treatment of multiple actinic keratoses with solaraze and actikerall. AB - Interest is increasing in the use of sequential or combined therapeutic modalities for spot or area treatment of actinic keratoses (AKs) to achieve complete sustained remission. For multiple lesions in a contained area, topical treatment offers less discomfort, better cosmesis and greater patient convenience than destructive/ablative techniques. Twelve patients with multiple grade I and II AK lesions of the scalp (cases 1-10) or the dorsum of the hand (cases 11 and 12), most with a history of recurrence, were treated with Solaraze gel (3% diclofenac sodium in 2.5% hyaluronic acid) twice daily for 12 weeks, followed by a 2-week treatment-free interval, then Actikerall cutaneous solution (5 fluorouracil 5 mg/g and salicylic acid 100 mg/g) once daily for up to 6 weeks as required. Sequential treatment provided complete (clinical and histological) clearance in 8/10 male patients. Two patients with numerous lesions had partial clearance (significant improvement) and the remaining few lesions were treated with erbium laser. Both female patients achieved complete clinical clearance with sequential treatment. Solaraze/Actikerall were well tolerated. A case of contact dermatitis with Solaraze resolved after discontinuation and the patient progressed to treatment with Actikerall. Local application site reactions resolved upon treatment completion. Topical lesion-directed sequential treatment with Solaraze/Actikerall is a rational approach to treat patients with multiple AKs. Sequential treatment produces excellent clearance rates which are accompanied by relevant improvement in patients' quality of life. PMID- 25120468 TI - Keratoacanthoma accompanied by multiple lung squamous cell carcinomas developing in a renal transplant recipient. AB - Keratoacanthoma (KA) is a benign keratinocytic neoplasm that spontaneously regresses after 3-6 months and shares features with well-differentiated squamous cell carcinoma (SCC). An increased incidence of both KA and non-melanoma skin tumor, including SCC, is seen among immunosuppressed, organ-transplant recipients. In this report we describe a case of KA accompanied by multiple lung SCCs developing in a renal transplant recipient. PMID- 25120466 TI - Characterizing relationships of DTI, fMRI, and motor recovery in stroke rehabilitation utilizing brain-computer interface technology. AB - The relationship of the structural integrity of white matter tracts and cortical activity to motor functional outcomes in stroke patients is of particular interest in understanding mechanisms of brain structural and functional changes while recovering from stroke. This study aims to probe these underlying mechanisms using diffusion tensor imaging (DTI) and fMRI measures. We examined the structural integrity of the posterior limb of the internal capsule (PLIC) using DTI and corticomotor activity using motor-task fMRI in stroke patients who completed up to 15 sessions of rehabilitation therapy using Brain-Computer Interface (BCI) technology. We hypothesized that (1) the structural integrity of PLIC and corticomotor activity are affected by stroke; (2) changes in structural integrity and corticomotor activity following BCI intervention are related to motor recovery; (3) there is a potential relationship between structural integrity and corticomotor activity. We found that (1) the ipsilesional PLIC showed significantly decreased fractional anisotropy (FA) values when compared to the contralesional PLIC; (2) lower ipsilesional PLIC-FA values were significantly associated with worse motor outcomes (i.e., ipsilesional PLIC-FA and motor outcomes were positively correlated.); (3) lower ipsilesional PLIC-FA values were significantly associated with greater ipsilesional corticomotor activity during impaired-finger-tapping-task fMRI (i.e., ipsilesional PLIC-FA and ipsilesional corticomotor activity were negatively correlated), with an overall bilateral pattern of corticomotor activity observed; and (4) baseline FA values predicted motor recovery assessed after BCI intervention. These findings suggest that (1) greater vs. lesser microstructural integrity of the ipsilesional PLIC may contribute toward better vs. poor motor recovery respectively in the stroke affected limb and demand lesser vs. greater cortical activity respectively from the ipsilesional motor cortex; and that (2) PLIC-FA is a promising biomarker in tracking and predicting motor functional recovery in stroke patients receiving BCI intervention. PMID- 25120469 TI - Rothmund-thomson syndrome: a 13-year follow-up. AB - Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder presenting with poikiloderma and other clinical features, affecting the bones and eyes and, in type II RTS, presenting an increased risk for malignancy. With about 300 cases reported so far, we present a 13-year follow-up including clinical images, X-rays and genetic analysis. A 13-month-old female started with a facial rash with blisters on her cheeks and limbs at the age of 3 months along with congenital hypoplastic thumbs, frontal bossing and fine hair, eyebrows and eyelashes. The patient was lost to follow-up and returned 12 years later with palmoplantar hyperkeratotic lesions, short stature, disseminated poikiloderma and sparse scalp hair, with absence of eyelashes and eyebrows. Radiographic analysis showed radial ray defect, absence of the thumb and three wrist carpal bones, and reduced bone density. Gene sequencing for the RECQL4 helicase gene revealed a mutation on each allele. RTS is a rare disease, and in this patient we observed the evolution of her skin lesions and other clinical features, which were important for the classification of type II RTS. The next years will provide even more information on this rare disease. PMID- 25120470 TI - Primary Duodenal Adenocarcinoma without Stenosis: A Case Report with a Brief Literature Review. AB - This article focuses on the symptomatic and diagnostic problems of primary duodenal adenocarcinoma (PDA) by way of two case reports and a literature review. An 85-year-old woman with an adenocarcinoma in the 1st duodenal portion was offered palliative care. A 90-year-old woman with an adenocarcinoma in the 3rd duodenal portion was also offered palliative care. A unique finding in the two cases reported herein is that PDA did not cause stenosis and occlusion of the lumen. As no reports of PDA without stenosis have been published so far, these cases may add to our knowledge of PDA. The diagnosis of PDA is often delayed because its symptoms may be absent until the tumor has progressed, thus leading to a delay of several months. Patients typically present with a long history of variable and vague symptoms, and many are diagnosed with advanced disease. As regards clinical manifestations, abdominal pain is the most frequent symptom. The majority of these tumors are found to have infiltrated the duodenal wall at presentation, with many being unresectable due to local and distal invasion. Esophagogastroduodenoscopy and gastrointestinal barium radiography are the main diagnostic tests for PDA, detecting 88.6 and 83.3% of tumors, respectively. In some cases, ultrasonography or computed tomography are useful for detecting PDA and determining vascular invasion. PMID- 25120471 TI - Use of Core Needle Biopsy rather than Fine-Needle Aspiration Cytology in the Diagnostic Approach of Breast Cancer. AB - BACKGROUND AND AIMS: In the following study case, we reviewed breast ultrasound guided core needle biopsy (CNB), using Mammotome (vacuum-assisted breast biopsy) and Tru-cut, carried out on palpable and nonpalpable uncertain breast lumps or malignant large lesions to be submitted to neoadjuvant chemotherapy. MATERIAL AND METHODS: Examinations were conducted during a 4-year period of clinical activity in a highly specialized center, from December 2009 to December 2013, in 712 patients previously subjected to fine-needle aspiration cytology (FNAC). RESULTS: The results demonstrated that among the 712 breast biopsies, in many cases FNAC was not conclusive, and therefore we proceeded with the echo-guided biopsy, through which we were able to collect sufficient material for the histological examination in order to direct patients to surgery or follow-up. CONCLUSIONS: CNB is far superior to FNAC, especially in cases of uncertainty, where it is preferable to proceed directly with CNB, which may also determine additional prognostic and predictive markers. Initially FNAC is less expensive, but the actual costs involved tend to be higher for FNAC as it is less accurate and a CNB is often required. In accordance with recent publications, we can confirm the full validity of CNB in the diagnostic approach of breast lesions. PMID- 25120473 TI - Severe dermatologic reactions with bendamustine: a case series. AB - Cutaneous drug reactions make up the largest proportion of adverse events in the medical field. Causality, in particular, is difficult to determine, and therefore, preventing recurrent reactions can be challenging. Bendamustine was initially thought to be a well-tolerated chemotherapy agent with few side effects aside from bone marrow suppression. However, the incidence of cutaneous reactions reported is rising. We describe three such reactions in relation to bendamustine administration in hopes of adding to the awareness of such side effects. PMID- 25120472 TI - Horrifying Basal cell carcinoma: cytological, immunohistochemical, and ultrastructural findings. AB - Basal cell carcinoma (BCC) is a slow-growing and frequently occurring tumor of the eyelids. Among BCC cases, there is a subtype of aggressive cases called horrifying BCC (HBCC). There are also rare BCC cases that show neuroendocrine differentiation. Here, we describe a case of HBCC with neuroendocrine differentiation. The patient, a 41-year-old woman, presented with abnormal left eye tearing and left cheek pain. On computed tomography imaging, a tumor that extended to the left orbit was detected in the left cheek. On cytological examination of fine-needle aspiration (FNA) samples, the tumor cells were observed as sheet-like clusters and single bare nuclei with a clear background; peripheral palisading was not clearly seen. On examination of the biopsy specimen taken after FNA, the tumor was found to be composed of cancer cell nests with scattered peripheral palisading in the dermis. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7 and CD56 and were negative for CK20, synaptophysin, and chromogranin A. Membrane-bound dense-core granules were detected on ultrastructural study. A HBCC case with neuroendocrine differentiation has not been previously reported. The correlation between the presence of neuroendocrine differentiation in HBCC and patient prognosis should be further studied. PMID- 25120474 TI - Massive bilateral serous retinal detachment in a case of hypertensive chorioretinopathy. AB - INTRODUCTION: Systemic high blood pressure is related to a variety of retinal manifestations. We present an atypical case of hypertensive chorioretinopathy with massive bilateral serous retinal detachment. CASE REPORT: A 26-year-old male with a genitourinary malformation and secondary grade IV chronic kidney failure as well as high blood pressure complained of acute vision loss. Dilated fundus examination evidenced a bilateral serous retinal detachment with macular involvement. The patient was unresponsive to oral antihypertensive therapy and dialysis treatment. The serous retinal detachment progressively decreased after the restoration of dialysis and antihypertensive therapy. The final visual acuity was 0.50 in both eyes. DISCUSSION: In cases of serous macular detachment, it is mandatory to rule out different systemic and ocular diseases. The presence of uncontrolled high blood pressure may produce aggressive bilateral retinal changes, thus hypertension must be under early and strict control in order to improve the visual outcomes. PMID- 25120475 TI - Swept-source optical coherence tomographic findings of choroidal osteoma. AB - PURPOSE: To report the morphologic features of a choroidal osteoma using swept source optical coherence tomography (SS-OCT) and fundus autofluorescence (FAF). METHODS: Two eyes of two cases with a choroidal osteoma were studied using SS-OCT and FAF. RESULTS: The location of the tumor was circumpapillary without macular involvement in case 1 and juxtapapillary with macular involvement in case 2. Both cases had a mixture of calcified and decalcified areas, and a concomitant choroidal neovascularization was found in case 2. The FAF images showed decreased autofluorescence in the central decalcified regions and relatively preserved fluorescence in marginal calcified regions in both cases. SS-OCT revealed a normal inner retina and an abnormal outer retina in both cases, and subretinal fluid in case 2. The calcified regions appeared sponge-like and were multilayered in case 2. A lamellar reflective pattern was observed in the decalcified regions in case 1, and hyperreflective mound-like areas were observed in both cases. SS OCT demonstrated hyperreflective areas above Bruch's membrane accompanied by disruption of Bruch's membrane in case 1. The chorioscleral border was visible in both cases. CONCLUSIONS: The FAF pattern in the calcified and decalcified areas of the choroidal osteoma may correspond to the different stage of tumor evolution. The SS-OCT findings indicate that choroidal osteomas can have characteristic reflective patterns and alterations of the overlying retina. PMID- 25120476 TI - Systemic inflammation, blood-brain barrier vulnerability and cognitive/non cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. AB - The incidence of dementia is increasing at an alarming rate, and has become a major public health concern. Alzheimer disease (AD) is the most common form of dementia and is characterized by progressive cognitive impairment. In addition to classical neuropathological features such as amyloid plaques and neurofibrillary tangles (NFT), accumulation of activated immune cells has been documented in the AD brain, suggesting a contribution of neuroinflammation in the pathogenesis of AD. Besides cognitive deterioration, non-cognitive symptoms, such as agitation, aggression, depression and psychosis, are often observed in demented patients, including those with AD, and these neuropsychological symptoms place a heavy burden on caregivers. These symptoms often exhibit sudden onset and tend to fluctuate over time, and in many cases, they are triggered by an infection in peripheral organs, suggesting that inflammation plays an important role in the pathogenesis of these non-cognitive symptoms. However, there is no mechanistic explanation for the relationship between inflammation and neuropsychiatric symptoms. Observations from experimental mouse models indicate that alteration of brain blood vessels, especially blood-brain barrier (BBB) dysfunction, may contribute to the relationship. The current review summarizes the results from recent studies on the relationship between inflammation and AD, while focusing on cerebrovascular alterations, which might provide an insight into the pathogenesis of cognitive/non-cognitive symptoms in AD patients and suggest a basis for the development of new therapeutic treatments for these conditions. PMID- 25120479 TI - Inflammatory nociception responses do not vary with age, but diminish with the pain history. AB - Some of the relevant factors that must be considered when dealing with old age include its growing numbers in the general population and pain contention in this age group. In this sense, it is important to study whether antinociceptive responses change with age. To elucidate this point, persistent pain in animals is the preferred model. In addition, the response to inflammatory pain in the same individual must be explored along its lifetime. Male Wistar rats were infiltrated with carrageenan (50 MUl intraplantar) and tested 3 h and 24 h after injection using thermal (plantar test) and mechanociceptive tests (von Frey). The rats were divided into the following groups: (a) young rats infiltrated for the first time at 12 weeks of age and re-infiltrated at 15 and 17 weeks; (b) adult rats infiltrated for the first time at 28 weeks of age and re-infiltrated at 44 and 56 weeks; and (c) old rats infiltrated for the first time at 56 weeks of age and re infiltrated at 72 weeks. The rats tested for the first time at 12 and 56 weeks of age showed hyperalgesia due to carrageenan infiltration at 3 h and 24 h after injection. This result showed that old rats maintain the same antialgesic response due to inflammation. However, when the injection was repeated in the three age groups, the latency to the thermal and mechanociceptive responses at 3 h is increased when compared to animals exposed for the first time to inflammation. The response to thermal and mechanociception in old rats is the same as in young animals as long as the nociceptive stimulus is not repeated. The repetition of the stimulus produces changes compatible with desensitization of the response and evidences the significance of algesic stimulus repetition in the same individual rather than the age of the individual. PMID- 25120478 TI - Effects of combined MAO-B inhibitors and levodopa vs. monotherapy in Parkinson's disease. AB - BACKGROUND: Prior studies report that monoamine oxidases inhibitors (MAO-I) when used as an adjunct to levodopa ameliorate motor symptoms in Parkinson's disease (PD), but this was not tested in relation to cognitive or psychiatric measures. OBJECTIVE: Here, we tested the effects of MAO-I as an adjunct to levodopa, in comparison to levodopa or dopamine (DA) agonists alone, on various cognitive, affective and quality of life measures. METHODS: We studied three groups of subjects: healthy controls, PD patients on combined levodopa and MAO-I, and PD patients on levodopa or DA agonists only. RESULTS: We found that compared to monotherapy, combined MAO-I and levodopa seemed to improve cognition, including probabilistic learning, working memory and executive functions. There were no differences between the different medication regimes on deterministic learning, attention or memory recall. It was also found that MAO-I as an adjunct to levodopa improves affective measures such as depression, apathy, anxiety and quality of life. Interestingly, this enhancing effect of combined levodopa and MAO-I was more pronounced in PD patients with severe akinesia, compared to patients with severe tremor. CONCLUSION: Our data are in agreement with (a) the Continuous Dopaminergic Stimulation (CDS) theory which states that continuous stimulation of the basal ganglia enhances motor, psychiatric and cognitive functions in PD patients; and/or (b) findings that MAO-I increase the bioavailability of monoamines that have beneficial effects on motor and behavioral dysfunction in PD. PMID- 25120480 TI - Graph analysis of verbal fluency test discriminate between patients with Alzheimer's disease, mild cognitive impairment and normal elderly controls. AB - Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment-subtypes amnestic (aMCI) and amnestic multiple domain (a+mdMCI)-and patients with Alzheimer's disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGA). The individuals were compared when divided in three (NC-MCI-AD) and four (NC-aMCI-a+mdMCI-AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly. PMID- 25120477 TI - Alzheimer's disease: relevant molecular and physiopathological events affecting amyloid-beta brain balance and the putative role of PPARs. AB - Alzheimer's disease (AD) is the most common form of age-related dementia. With the expected aging of the human population, the estimated morbidity of AD suggests a critical upcoming health problem. Several lines of research are focused on understanding AD pathophysiology, and although the etiology of the disease remains a matter of intense debate, increased brain levels of amyloid beta (Abeta) appear to be a critical event in triggering a wide range of molecular alterations leading to AD. It has become evident in recent years that an altered balance between production and clearance is responsible for the accumulation of brain Abeta. Moreover, Abeta clearance is a complex event that involves more than neurons and microglia. The status of the blood-brain barrier (BBB) and choroid plexus, along with hepatic functionality, should be considered when Abeta balance is addressed. Furthermore, it has been proposed that exposure to sub-toxic concentrations of metals, such as copper, could both directly affect these secondary structures and act as a seeding or nucleation core that facilitates Abeta aggregation. Recently, we have addressed peroxisomal proliferator-activated receptors (PPARs)-related mechanisms, including the direct modulation of mitochondrial dynamics through the PPARgamma-coactivator-1alpha (PGC-1alpha) axis and the crosstalk with critical aging- and neurodegenerative related cellular pathways. In the present review, we revise the current knowledge regarding the molecular aspects of Abeta production and clearance and provide a physiological context that gives a more complete view of this issue. Additionally, we consider the different structures involved in AD-altered Abeta brain balance, which could be directly or indirectly affected by a nuclear receptor (NR)/PPAR-related mechanism. PMID- 25120482 TI - Sarcopenia and physical frailty: two sides of the same coin. PMID- 25120481 TI - Amylin and its analogs: a friend or foe for the treatment of Alzheimer's disease? AB - Amylin, a gut-brain axis hormone, and amyloid-beta peptides (Abeta), a major component of the Alzheimer's disease (AD) brain, share several features, including similar beta-sheet secondary structures, binding to the same receptor and being degraded by the same protease, insulin degrading enzyme (IDE). However, while amylin readily crosses the blood brain barrier (BBB) and mediates several activities including improving glucose metabolism, relaxing cerebrovascular structure, modulating inflammatory reaction and perhaps enhancing neural regeneration, Abeta has no known physiological functions. Thus, abundant Abeta in the AD brain could block or interfere with the binding of amylin to its receptor and hinder its functions. Recent studies using animal models for AD demonstrate that amylin and its analog reduce the AD pathology in the brain and improve cognitive impairment in AD. Given that, in addition to amyloid plaques and neurofibrillary tangles, perturbed cerebral glucose metabolism and cerebrovascular damage are the hallmarks of the AD brain, we propose that giving exogenous amylin type peptides have the potential to become a new avenue for the diagnosis and therapeutic of AD. Although amylin's property of self-aggregation may be a limitation to developing it as a therapeutic for AD, its clinical analog, pramlintide containing 3 amino acid differences from amylin, does not aggregate like human amylin, but more potently mediates amylin's activities in the brain. Pramlintide is an effective drug for diabetes with a favorable profile of safety. Thus a randomized, double-blind, placebo-controlled clinical trial should be conducted to examine the efficacy of pramlintide for AD. This review summarizes the knowledge and findings on amylin type peptides and discuss pros and cons for their potential for AD. PMID- 25120484 TI - From industrial research to academic discoveries, toward a new concept of partnership: the Biomathics model. PMID- 25120483 TI - Relationships between Personality Traits, Medial Temporal Lobe Atrophy, and White Matter Lesion in Subjects Suffering from Mild Cognitive Impairment. AB - Mild cognitive impairment (MCI) is a heterogeneous cognitive status that can be a prodromal stage of Alzheimer's disease (AD). It is particularly relevant to focus on prodromal stages of AD such as MCI, because patho-physiological abnormalities of AD start years before the dementia stage. Medial temporal lobe (MTL) atrophy resulting from AD lesions and cerebrovascular lesions [i.e., white matter lesions (WML), lacunar strokes, and strokes] are often revealed concurrently on magnetic resonance imaging (MRI) in MCI subjects. Personality changes have been reported to be associated with MCI status and early AD. More specifically, an increase in neuroticism and a decrease in conscientiousness have been reported, suggesting that higher and lower scores, respectively, in neuroticism and conscientiousness are associated with an increased risk of developing the disease. However, personality changes have not been studied concomitantly with pathological structural brain alterations detected on MRI in patients suffering from MCI. Therefore, the objective of the present study was to assess the relationship between MTL atrophy, WML, lacunar strokes, and personality traits in such patients. The severity of WML was strongly associated with lower levels of conscientiousness and higher levels of neuroticism. Conversely, no association was detected between personality traits and the presence of lacunar strokes or MTL atrophy. Altogether, these results strongly suggest that personality changes occurring in a MCI population, at high risk of AD, are associated with WML, which can induce executive dysfunctions, rather than with MTL atrophy. PMID- 25120485 TI - Implementation of pharmacokinetic and pharmacodynamic strategies in early research phases of drug discovery and development at Novartis Institute of Biomedical Research. AB - Characterizing the relationship between the pharmacokinetics (PK, concentration vs. time) and pharmacodynamics (PD, effect vs. time) is an important tool in the discovery and development of new drugs in the pharmaceutical industry. The purpose of this publication is to serve as a guide for drug discovery scientists toward optimal design and conduct of PK/PD studies in the research phase. This review is a result of the collaborative efforts of DMPK scientists from various Metabolism and Pharmacokinetic (MAP) departments of the global organization Novartis Institute of Biomedical Research (NIBR). We recommend that PK/PD strategies be implemented in early research phases of drug discovery projects to enable successful transition to drug development. Effective PK/PD study design, analysis, and interpretation can help scientists elucidate the relationship between PK and PD, understand the mechanism of drug action, and identify PK properties for further improvement and optimal compound design. Additionally, PK/PD modeling can help increase the translation of in vitro compound potency to the in vivo setting, reduce the number of in vivo animal studies, and improve translation of findings from preclinical species into the clinical setting. This review focuses on three important elements of successful PK/PD studies, namely partnership among key scientists involved in the study execution; parameters that influence study designs; and data analysis and interpretation. Specific examples and case studies are highlighted to help demonstrate key points for consideration. The intent is to provide a broad PK/PD foundation for colleagues in the pharmaceutical industry and serve as a tool to promote appropriate discussions on early research project teams with key scientists involved in PK/PD studies. PMID- 25120486 TI - The IRP/IRE system in vivo: insights from mouse models. AB - Iron regulatory proteins 1 and 2 (IRP1 and IRP2) post-transcriptionally control the expression of several mRNAs encoding proteins of iron, oxygen and energy metabolism. The mechanism involves their binding to iron responsive elements (IREs) in the untranslated regions of target mRNAs, thereby controlling mRNA translation or stability. Whereas IRP2 functions solely as an RNA-binding protein, IRP1 operates as either an RNA-binding protein or a cytosolic aconitase. Early experiments in cultured cells established a crucial role of IRPs in regulation of cellular iron metabolism. More recently, studies in mouse models with global or localized Irp1 and/or Irp2 deficiencies uncovered new physiological functions of IRPs in the context of systemic iron homeostasis. Thus, IRP1 emerged as a key regulator of erythropoiesis and iron absorption by controlling hypoxia inducible factor 2alpha (HIF2alpha) mRNA translation, while IRP2 appears to dominate the control of iron uptake and heme biosynthesis in erythroid progenitor cells by regulating the expression of transferrin receptor 1 (TfR1) and 5-aminolevulinic acid synthase 2 (ALAS2) mRNAs, respectively. Targeted disruption of either Irp1 or Irp2 in mice is associated with distinct phenotypic abnormalities. Thus, Irp1(-/-) mice develop polycythemia and pulmonary hypertension, while Irp2(-/-) mice present with microcytic anemia, iron overload in the intestine and the liver, and neurologic defects. Combined disruption of both Irp1 and Irp2 is incombatible with life and leads to early embryonic lethality. Mice with intestinal- or liver-specific disruption of both Irps are viable at birth but die later on due to malabsorption or liver failure, respectively. Adult mice lacking both Irps in the intestine exhibit a profound defect in dietary iron absorption due to a "mucosal block" that is caused by the de-repression of ferritin mRNA translation. Herein, we discuss the physiological function of the IRE/IRP regulatory system. PMID- 25120487 TI - Drug elucidation: invertebrate genetics sheds new light on the molecular targets of CNS drugs. AB - Many important drugs approved to treat common human diseases were discovered by serendipity, without a firm understanding of their modes of action. As a result, the side effects and interactions of these medications are often unpredictable, and there is limited guidance for improving the design of next-generation drugs. Here, we review the innovative use of simple model organisms, especially Caenorhabditis elegans, to gain fresh insights into the complex biological effects of approved CNS medications. Whereas drug discovery involves the identification of new drug targets and lead compounds/biologics, and drug development spans preclinical testing to FDA approval, drug elucidation refers to the process of understanding the mechanisms of action of marketed drugs by studying their novel effects in model organisms. Drug elucidation studies have revealed new pathways affected by antipsychotic drugs, e.g., the insulin signaling pathway, a trace amine receptor and a nicotinic acetylcholine receptor. Similarly, novel targets of antidepressant drugs and lithium have been identified in C. elegans, including lipid-binding/transport proteins and the SGK-1 signaling pathway, respectively. Elucidation of the mode of action of anesthetic agents has shown that anesthesia can involve mitochondrial targets, leak currents, and gap junctions. The general approach reviewed in this article has advanced our knowledge about important drugs for CNS disorders and can guide future drug discovery efforts. PMID- 25120489 TI - Analysis of co-assembly and co-localization of ameloblastin and amelogenin. AB - Epithelially-derived ameloblasts secrete extracellular matrix proteins including amelogenin, enamelin, and ameloblastin. Complex intermolecular interactions among these proteins are believed to be important in controlling enamel formation. Here we provide in vitro and in vivo evidence of co-assembly and co-localization of ameloblastin with amelogenin using both biophysical and immunohistochemical methods. We performed co-localization studies using immunofluorescence confocal microscopy with paraffin-embedded tissue sections from mandibular molars of mice at 1, 5, and 8 days of age. Commercially-available ameloblastin antibody (M300) against mouse ameloblastin residues 107-407 and an antibody against full-length recombinant mouse (rM179) amelogenin were used. Ameloblastin-M300 clearly reacted along the secretory face of ameloblasts from days 1-8. Quantitative co localization was analyzed (QCA) in several configurations by choosing appropriate regions of interest (ROIs). Analysis of ROIs along the secretory face of ameloblasts revealed that at day 1, very high percentages of both the ameloblastin and amelogenin co-localized. At day 8 along the ameloblast cells the percentage of co-localization remained high for the ameloblastin whereas co localization percentage was reduced for amelogenin. Analysis of the entire thickness on day 8 revealed no significant co-localization of amelogenin and ameloblastin. With the progress of amelogenesis and ameloblastin degradation, there was a segregation of ameloblastin and co-localization with the C-terminal region decreased. CD spectra indicated that structural changes in ameloblastin occurred upon addition of amelogenin. Our data suggest that amelogenin ameloblastin complexes may be the functional entities at the early stage of enamel mineralization. PMID- 25120490 TI - Comparison of two mouse ameloblast-like cell lines for enamel-specific gene expression. AB - Ameloblasts are ectoderm-derived cells that produce an extracellular enamel matrix that mineralizes to form enamel. The development and use of immortalized cell lines, with a stable phenotype, is an important contribution to biological studies as it allows for the investigation of molecular activities without the continuous need for animals. In this study we compare the expression profiles of enamel-specific genes in two mouse derived ameloblast-like cell lines: LS8 and ALC cells. Quantitative PCR analysis indicates that, relative to each other, LS8 cells express greater mRNA levels for genes that define secretory-stage activities (Amelx, Ambn, Enam, and Mmp20), while ALC express greater mRNA levels for genes that define maturation-stage activities (Odam and Klk4). Western blot analyses show that Amelx, Ambn, and Odam proteins are detectable in ALC, but not LS8 cells. Unstimulated ALC cells form calcified nodules, while LS8 cells do not. These data provide greater insight as to the suitability of both cell lines to contribute to biological studies on enamel formation and biomineralization, and highlight some of the strengths and weaknesses when relying on enamel epithelial organ-derived cell lines to study molecular activities of amelogenesis. PMID- 25120488 TI - Nano-scale measurement of biomolecules by optical microscopy and semiconductor nanoparticles. AB - Over the past decade, great developments in optical microscopy have made this technology increasingly compatible with biological studies. Fluorescence microscopy has especially contributed to investigating the dynamic behaviors of live specimens and can now resolve objects with nanometer precision and resolution due to super-resolution imaging. Additionally, single particle tracking provides information on the dynamics of individual proteins at the nanometer scale both in vitro and in cells. Complementing advances in microscopy technologies has been the development of fluorescent probes. The quantum dot, a semi-conductor fluorescent nanoparticle, is particularly suitable for single particle tracking and super-resolution imaging. This article overviews the principles of single particle tracking and super resolution along with describing their application to the nanometer measurement/observation of biological systems when combined with quantum dot technologies. PMID- 25120491 TI - Need for multi-scale systems to identify spindle orientation regulators relevant to tissue disorganization in solid cancers. PMID- 25120493 TI - Sympathetic dysfunction in vasovagal syncope and the postural orthostatic tachycardia syndrome. AB - Orthostatic intolerance is the inability to tolerate the upright posture and is relieved by recumbence. It most commonly affects young women and has a major impact on quality of life and psychosocial well-being. Several forms of orthostatic intolerance have been described. The most common one is the recurrent vasovagal syncope (VVS) phenotype which presents as a transient and abrupt loss of consciousness and postural tone that is followed by rapid recovery. Another common type of orthostatic intolerance is the postural orthostatic tachycardia syndrome (POTS) which is characterized by an excessive rise in heart rate upon standing and is associated with symptoms of presyncope such as light-headedness, fatigue, palpitations, and nausea. Maintenance of arterial pressure under condition of reduced central blood volume during the orthostasis is accomplished in large part through sympathetic efferent nerve traffic to the peripheral vasculature. Therefore sympathetic nervous system (SNS) dysfunction is high on the list of possible contributors to the pathophysiology of orthostatic intolerance. Investigations into the role of the SNS in orthostatic intolerance have yielded mixed results. This review outlines the current knowledge of the function of the SNS in both VVS and POTS. PMID- 25120495 TI - Can exercise increase fitness and reduce weight in patients with schizophrenia and depression? AB - BACKGROUND: Psychiatric patients have a reduced life expectancy of 15-20 years compared with the general population. Most years of lost life are due to the excess mortality from somatic diseases. Sedentary lifestyle and medication is partly responsible for the high frequency of metabolic syndrome in this patient group and low levels of physical activity is associated with increased risk of cardiovascular disease, diabetes, and all-cause mortality. This study aimed to review trials allocating patients with either schizophrenia or depression to exercise interventions for effect on cardiovascular fitness, strength, and weight. METHODS: We searched PubMed, Embase, and PsycINFO including randomized clinical trial allocating patients with either schizophrenia or depression to isolated exercise interventions. RESULTS: We identified five trials including patients with schizophrenia (n = 94) and found little evidence that exercise could increase cardiovascular fitness or decrease weight. Nine exercise trials for patients with depression (n = 892) were identified increasing cardiovascular fitness by 11-30% and strength by 33-37%. No evidence in favor of exercise for weight reduction was found. CONCLUSION: Based on the current evidence isolated exercise interventions are unlikely to improve cardiovascular fitness or induce weight loss in patients with schizophrenia. In patients with depression, exercise interventions are likely to induce clinically relevant short term effects, however, due to lack of reporting, little is known about the effect on weight reduction and cardiovascular fitness. Future exercise trials regarding patients with mental illness should preferably measure changes in cardiovascular strength, repetition maximum, and anthropometric outcomes. Ideally, participants should be assessed beyond the intervention to identify long lasting effects. PMID- 25120492 TI - Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic inflammation. AB - Plasmacytoid dendritic cells (pDCs) are a specialized subset of DCs that links innate and adaptive immunity. They sense viral and bacterial pathogens and release high levels of Type I interferons (IFN-I) in response to infection. pDCs were shown to contribute to inflammatory responses in the steady state and in pathology. In atherosclerosis, pDCs are involved in priming vascular inflammation and atherogenesis through production of IFN-I and chemokines that attract inflammatory cells to inflamed sites. pDCs also contribute to the proinflammatory activation of effector T cells, cytotoxic T cells, and conventional DCs. However, tolerogenic populations of pDCs are found that suppress atherosclerosis associated inflammation through down-regulation of function and proliferation of proinflammatory T cell subsets and induction of regulatory T cells with potent immunomodulatory properties. Notably, atheroprotective tolerogenic DCs could be induced by certain self-antigens or bacterial antigens that suggests for great therapeutic potential of these DCs for development of DC-based anti-atherogenic vaccines. PMID- 25120494 TI - Tenascin-C and mechanotransduction in the development and diseases of cardiovascular system. AB - Living tissue is composed of cells and extracellular matrix (ECM). In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain tissue structure. ECM is also important for biological signaling, which influences various cellular functions in embryonic development, and physiological/pathological responses to extrinsic stimuli. Among ECM molecules, increased attention has been focused on matricellular proteins. Matricellular proteins are a growing group of non structural ECM proteins highly up-regulated at active tissue remodeling, serving as biological mediators. Tenascin-C (TNC) is a typical matricellular protein, which is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion. The expression is tightly regulated, dependent on the microenvironment, including various growth factors, cytokines, and mechanical stress. In the heart, TNC appears in a spatiotemporal-restricted manner during early stages of development, sparsely detected in normal adults, but transiently re-expressed at restricted sites associated with tissue injury and inflammation. Similarly, in the vascular system, TNC is strongly up-regulated during embryonic development and under pathological conditions with an increase in hemodynamic stress. Despite its intriguing expression pattern, cardiovascular system develops normally in TNC knockout mice. However, deletion of TNC causes acute aortic dissection (AAD) under strong mechanical and humoral stress. Accumulating reports suggest that TNC may modulate the inflammatory response and contribute to elasticity of the tissue, so that it may protect cardiovascular tissue from destructive stress responses. TNC may be a key molecule to control cellular activity during development, adaptation, or pathological tissue remodeling. PMID- 25120496 TI - Trophic Mechanisms for Exercise-Induced Stress Resilience: Potential Role of Interactions between BDNF and Galanin. AB - Current concepts of the neurobiology of stress-related disorders, such as anxiety and depression emphasize disruptions in neural plasticity and neurotrophins. The potent trophic actions of exercise, therefore, represent not only an effective means for prevention and treatment of these disorders, they also afford the opportunity to employ exercise paradigms as a basic research tool to uncover the neurobiological mechanisms underlying these disorders. Novel approaches to studying stress-related disorders focus increasingly on trophic factor signaling in corticolimbic circuits that both mediate and regulate cognitive, behavioral, and physiological responses to deleterious stress. Recent evidence demonstrates that the neural plasticity supported by these trophic mechanisms is vital for establishing and maintaining resilience to stress. Therapeutic interventions that promote these mechanisms, be they pharmacological, behavioral, or environmental, may therefore prevent or reverse stress-related mental illness by enhancing resilience. The present paper will provide an overview of trophic mechanisms responsible for the enhancement of resilience by voluntary exercise with an emphasis on brain-derived neurotrophic factor, galanin, and interactions between these two trophic factors. PMID- 25120497 TI - Timing and time perception: A selective review and commentary on recent reviews. PMID- 25120499 TI - Testing strong factorial invariance using three-level structural equation modeling. AB - Within structural equation modeling, the most prevalent model to investigate measurement bias is the multigroup model. Equal factor loadings and intercepts across groups in a multigroup model represent strong factorial invariance (absence of measurement bias) across groups. Although this approach is possible in principle, it is hardly practical when the number of groups is large or when the group size is relatively small. Jak et al. (2013) showed how strong factorial invariance across large numbers of groups can be tested in a multilevel structural equation modeling framework, by treating group as a random instead of a fixed variable. In the present study, this model is extended for use with three level data. The proposed method is illustrated with an investigation of strong factorial invariance across 156 school classes and 50 schools in a Dutch dyscalculia test, using three-level structural equation modeling. PMID- 25120500 TI - Is there an inverted-U relationship between creativity and psychopathology? PMID- 25120498 TI - The role of arousal in the spontaneous regulation of emotions in healthy aging: a fMRI investigation. AB - Despite ample support for enhanced affective well-being and emotional stability in healthy aging, the role of potentially important dimensions, such as the emotional arousal, has not been systematically investigated in neuroimaging studies. In addition, the few behavioral studies that examined effects of arousal have produced inconsistent findings. The present study manipulated the arousal of pictorial stimuli to test the hypothesis that preserved emotional functioning in aging is modulated by the level of arousal, and to identify the associated neural correlates. Young and older healthy participants were presented with negative and neutral pictures, which they rated for emotional content, while fMRI data were recorded. There were three main novel findings regarding the neural mechanisms underlying the processing of negative pictures with different levels of arousal in young and older adults. First, the common engagement of the right amygdala in young and older adults was driven by high arousing negative stimuli. Second, complementing an age-related reduction in the subjective ratings for low arousing negative pictures, there were opposing patterns of activity in the rostral/ventral anterior cingulate cortex (ACC) and the amygdala, which showed increased vs. decreased responses, respectively, to low arousing negative pictures. Third, increased spontaneous activity in the ventral ACC/ventromedial prefrontal cortex (vmPFC) in older adults was linked to reduced ratings for low arousing negative pictures. Overall, these findings advance our understanding of the neural correlates underlying processing of negative emotions with different levels of arousal in the context of enhanced emotional functioning in healthy aging. Notably, the results support the idea that older adults have emotion regulation networks chronically activated, in the absence of explicit induction of the goal to regulate emotions, and that this effect is specific to low arousing negative emotions. PMID- 25120501 TI - Error management for musicians: an interdisciplinary conceptual framework. AB - Musicians tend to strive for flawless performance and perfection, avoiding errors at all costs. Dealing with errors while practicing or performing is often frustrating and can lead to anger and despair, which can explain musicians' generally negative attitude toward errors and the tendency to aim for flawless learning in instrumental music education. But even the best performances are rarely error-free, and research in general pedagogy and psychology has shown that errors provide useful information for the learning process. Research in instrumental pedagogy is still neglecting error issues; the benefits of risk management (before the error) and error management (during and after the error) are still underestimated. It follows that dealing with errors is a key aspect of music practice at home, teaching, and performance in public. And yet, to be innovative, or to make their performance extraordinary, musicians need to risk errors. Currently, most music students only acquire the ability to manage errors implicitly - or not at all. A more constructive, creative, and differentiated culture of errors would balance error tolerance and risk-taking against error prevention in ways that enhance music practice and music performance. The teaching environment should lay the foundation for the development of such an approach. In this contribution, we survey recent research in aviation, medicine, economics, psychology, and interdisciplinary decision theory that has demonstrated that specific error-management training can promote metacognitive skills that lead to better adaptive transfer and better performance skills. We summarize how this research can be applied to music, and survey-relevant research that is specifically tailored to the needs of musicians, including generic guidelines for risk and error management in music teaching and performance. On this basis, we develop a conceptual framework for risk management that can provide orientation for further music education and musicians at all levels. PMID- 25120502 TI - Parallel effects of memory set activation and search on timing and working memory capacity. AB - Accurately estimating a time interval is required in everyday activities such as driving or cooking. Estimating time is relatively easy, provided a person attends to it. But a brief shift of attention to another task usually interferes with timing. Most processes carried out concurrently with timing interfere with it. Curiously, some do not. Literature on a few processes suggests a general proposition, the Timing and Complex-Span Hypothesis: A process interferes with concurrent timing if and only if process performance is related to complex span. Complex-span is the number of items correctly recalled in order, when each item presented for study is followed by a brief activity. Literature on task switching, visual search, memory search, word generation and mental time travel supports the hypothesis. Previous work found that another process, activation of a memory set in long term memory, is not related to complex-span. If the Timing and Complex-Span Hypothesis is true, activation should not interfere with concurrent timing in dual-task conditions. We tested such activation in single task memory search task conditions and in dual-task conditions where memory search was executed with concurrent timing. In Experiment 1, activating a memory set increased reaction time, with no significant effect on time production. In Experiment 2, set size and memory set activation were manipulated. Activation and set size had a puzzling interaction for time productions, perhaps due to difficult conditions, leading us to use a related but easier task in Experiment 3. In Experiment 3 increasing set size lengthened time production, but memory activation had no significant effect. Results here and in previous literature on the whole support the Timing and Complex-Span Hypotheses. Results also support a sequential organization of activation and search of memory. This organization predicts activation and set size have additive effects on reaction time and multiplicative effects on percent correct, which was found. PMID- 25120503 TI - Using Bayes to get the most out of non-significant results. AB - No scientific conclusion follows automatically from a statistically non significant result, yet people routinely use non-significant results to guide conclusions about the status of theories (or the effectiveness of practices). To know whether a non-significant result counts against a theory, or if it just indicates data insensitivity, researchers must use one of: power, intervals (such as confidence or credibility intervals), or else an indicator of the relative evidence for one theory over another, such as a Bayes factor. I argue Bayes factors allow theory to be linked to data in a way that overcomes the weaknesses of the other approaches. Specifically, Bayes factors use the data themselves to determine their sensitivity in distinguishing theories (unlike power), and they make use of those aspects of a theory's predictions that are often easiest to specify (unlike power and intervals, which require specifying the minimal interesting value in order to address theory). Bayes factors provide a coherent approach to determining whether non-significant results support a null hypothesis over a theory, or whether the data are just insensitive. They allow accepting and rejecting the null hypothesis to be put on an equal footing. Concrete examples are provided to indicate the range of application of a simple online Bayes calculator, which reveal both the strengths and weaknesses of Bayes factors. PMID- 25120505 TI - Measuring the crowd within again: a pre-registered replication study. AB - According to the crowd within effect, the average of two estimates from one person tends to be more accurate than a single estimate of that person. The effect implies that the well documented wisdom of the crowd effect-the crowd's average estimate tends to be more accurate than the individual estimates-can be obtained within a single individual. In this paper, we performed a high-powered, pre-registered replication study of the original experiment. Our replication results are evaluated with the traditional null hypothesis significance testing approach, as well as with effect sizes and their confidence intervals. We adopted a co-pilot approach, in the sense that all analyses were performed independently by two researchers using different analysis software. Moreover, we report Bayes factors for all tests. We successfully replicated the crowd within effect, both when the second guess was made immediately after the first guess, as well as when it was made 3 weeks later. The experimental protocol, the raw data, the post processed data and the analysis code are available online. PMID- 25120507 TI - The role of both parents' attachment pattern in understanding childhood obesity. AB - Within the research area on the determinants of childhood obesity, a relatively new approach is the use of attachment theory to explore the mechanisms underlying children's obesity risk, especially considered as emotion regulation strategies in parent-child relationship. Few are the empirical researches that have addressed this issue. The empirical investigations have used self-report measures to assess adult attachment. In attachment studies, the use of interview methods and/or performance-based instruments is advised to evaluate the entire range of possible adult attachment patterns and comprehensively explain the emotional strategies, correlates, and consequences of individual differences in attachment system functioning. The aim of this study was to explore the extent to which both parents' attachment patterns serve as self-regulative mechanisms related to childhood overweight/obesity by the Adult Attachment Projective Picture System (AAP) in a sample of 44 mothers and fathers of children referred for obesity. Insecure attachment was found as a risk factor both for mothers and fathers. Also unresolved/disorganization was found to play a significant role in childhood obesity. The role of father's attachment was explored and findings suggested considering it in etiology and treatment of childhood obesity. PMID- 25120506 TI - Musicians are more consistent: Gestural cross-modal mappings of pitch, loudness and tempo in real-time. AB - Cross-modal mappings of auditory stimuli reveal valuable insights into how humans make sense of sound and music. Whereas researchers have investigated cross-modal mappings of sound features varied in isolation within paradigms such as speeded classification and forced-choice matching tasks, investigations of representations of concurrently varied sound features (e.g., pitch, loudness and tempo) with overt gestures-accounting for the intrinsic link between movement and sound-are scant. To explore the role of bodily gestures in cross-modal mappings of auditory stimuli we asked 64 musically trained and untrained participants to represent pure tones-continually sounding and concurrently varied in pitch, loudness and tempo-with gestures while the sound stimuli were played. We hypothesized musical training to lead to more consistent mappings between pitch and height, loudness and distance/height, and tempo and speed of hand movement and muscular energy. Our results corroborate previously reported pitch vs. height (higher pitch leading to higher elevation in space) and tempo vs. speed (increasing tempo leading to increasing speed of hand movement) associations, but also reveal novel findings pertaining to musical training which influenced consistency of pitch mappings, annulling a commonly observed bias for convex (i.e., rising-falling) pitch contours. Moreover, we reveal effects of interactions between musical parameters on cross-modal mappings (e.g., pitch and loudness on speed of hand movement), highlighting the importance of studying auditory stimuli concurrently varied in different musical parameters. Results are discussed in light of cross-modal cognition, with particular emphasis on studies within (embodied) music cognition. Implications for theoretical refinements and potential clinical applications are provided. PMID- 25120508 TI - Emotion and affect in mental imagery: do fear and anxiety manipulate mental rotation performance? AB - Little is known about the effects of fear as a basic emotion on mental rotation (MR) performance. We expected that the emotional arousal evoked by fearful stimuli presented prior to each MR trial would enhance MR performance. Regarding the influence of anxiety, high anxious participants are supposed to show slower responses and higher error rates in this specific visuo-spatial ability. Furthermore, with respect to the embodied cognition viewpoint we wanted to investigate if the influence of fear on MR performance is the same for egocentric and object-based transformations. To investigate this, we presented either negative or neutral images prior to each MR trial. Participants were allocated to the specific emotion in a randomized order. Results show that fear enhances MR performance, expressed by a higher MR speed. Interestingly, this influence is dependent on the type of transformation: it is restricted to egocentric rotations. Both observation of emotional stimuli and egocentric strategies are associated with left hemisphere activation which could explain a stronger influence on this type of transformation during observation. Another possible notion is the conceptual link between visuo-spatial perspective taking and empathy based on the co-activation of parietal areas. Stronger responses in egocentric transformations could result from this specific link. Regarding the influence of anxiety, participants with high scores on the trait-anxiety scale showed poor results in both reaction time and MR speed. Findings of impoverished recruitment of prefrontal attentional control in patients with high scores in trait anxiety could be the explanation for this reduced performance. PMID- 25120509 TI - Visual appearance interacts with conceptual knowledge in object recognition. AB - Objects contain rich visual and conceptual information, but do these two types of information interact? Here, we examine whether visual and conceptual information interact when observers see novel objects for the first time. We then address how this interaction influences the acquisition of perceptual expertise. We used two types of novel objects (Greebles), designed to resemble either animals or tools, and two lists of words, which described non-visual attributes of people or man made objects. Participants first judged if a word was more suitable for describing people or objects while ignoring a task-irrelevant image, and showed faster responses if the words and the unfamiliar objects were congruent in terms of animacy (e.g., animal-like objects with words that described human). Participants then learned to associate objects and words that were either congruent or not in animacy, before receiving expertise training to rapidly individuate the objects. Congruent pairing of visual and conceptual information facilitated observers' ability to become a perceptual expert, as revealed in a matching task that required visual identification at the basic or subordinate levels. Taken together, these findings show that visual and conceptual information interact at multiple levels in object recognition. PMID- 25120511 TI - Psychotherapy participants show increased physiological responsiveness to a lab stressor relative to matched controls. AB - Accumulating evidence indicates that psychotherapy participants show increased physiological responsiveness to stress. The purpose of the present study was to examine differences between individuals participating in outpatient psychotherapy and matched controls using an experimental design. Forty-two psychotherapy participants and 48 matched controls were assessed on cardiovascular and cortisol functioning at baseline, during the Trier Social Stress Test (TSST), and during a 20-min recovery period. Psychotherapy participants and matched controls did not differ at baseline or during the TSST on the physiological measures but psychotherapy participants had higher cortisol and heart rate (HR) during the recovery period. In regards to reactivity, cortisol increased during the recovery period for the psychotherapy participants but decreased for those in the matched control group. Psychotherapy participants experiencing clinically significant levels of distress displayed elevated systolic and diastolic blood pressure and HR during the TSST when compared to psychotherapy participants not experiencing clinically significant levels of distress. Overall, physiological reactivity to stress appears to be an important issue for those in psychotherapy and directly addressing this issue may help improve psychotherapy outcomes. PMID- 25120510 TI - Multi-domain computerized cognitive training program improves performance of bookkeeping tasks: a matched-sampling active-controlled trial. AB - Cognitive skills are important predictors of job performance, but the extent to which computerized cognitive training (CCT) can improve job performance in healthy adults is unclear. We report, for the first time, that a CCT program aimed at attention, memory, reasoning and visuo-spatial abilities can enhance productivity in healthy younger adults on bookkeeping tasks with high relevance to real-world job performance. 44 business students (77.3% female, mean age 21.4 +/- 2.6 years) were assigned to either (a) 20 h of CCT, or (b) 20 h of computerized arithmetic training (active control) by a matched sampling procedure. Both interventions were conducted over a period of 6 weeks, 3-4 1-h sessions per week. Transfer of skills to performance on a 60-min paper-based bookkeeping task was measured at three time points-baseline, after 10 h and after 20 h of training. Repeated measures ANOVA found a significant Group X Time effect on productivity (F = 7.033, df = 1.745; 73.273, p = 0.003) with a significant interaction at both the 10-h (Relative Cohen's effect size = 0.38, p = 0.014) and 20-h time points (Relative Cohen's effect size = 0.40, p = 0.003). No significant effects were found on accuracy or on Conners' Continuous Performance Test, a measure of sustained attention. The results are discussed in reference to previous findings on the relationship between brain plasticity and job performance. Generalization of results requires further study. PMID- 25120512 TI - A holistic intervention program for children from low socioeconomic status families. PMID- 25120504 TI - Elucidating unconscious processing with instrumental hypnosis. AB - Most researchers leverage bottom-up suppression to unlock the underlying mechanisms of unconscious processing. However, a top-down approach - for example via hypnotic suggestion - paves the road to experimental innovation and complementary data that afford new scientific insights concerning attention and the unconscious. Drawing from a reliable taxonomy that differentiates subliminal and preconscious processing, we outline how an experimental trajectory that champions top-down suppression techniques, such as those practiced in hypnosis, is uniquely poised to further contextualize and refine our scientific understanding of unconscious processing. Examining subliminal and preconscious methods, we demonstrate how instrumental hypnosis provides a reliable adjunct that supplements contemporary approaches. Specifically, we provide an integrative synthesis of the advantages and shortcomings that accompany a top-down approach to probe the unconscious mind. Our account provides a larger framework for complementing the results from core studies involving prevailing subliminal and preconscious techniques. PMID- 25120514 TI - Singing and social inclusion. AB - There is a growing body of neurological, cognitive, and social psychological research to suggest the possibility of positive transfer effects from structured musical engagement. In particular, there is evidence to suggest that engagement in musical activities may impact on social inclusion (sense of self and of being socially integrated). Tackling social exclusion and promoting social inclusion are common concerns internationally, such as in the UK and the EC, and there are many diverse Government ministries and agencies globally that see the arts in general and music in particular as a key means by which social needs can be addressed. As part of a wider evaluation of a national, Government-sponsored music education initiative for Primary-aged children in England ("Sing Up"), opportunity was taken by the authors, at the request of the funders, to assess any possible relationship between (a) children's developing singing behavior and development and (b) their social inclusion (sense of self and of being socially integrated). Subsequently, it was possible to match data from n = 6087 participants, drawn from the final 3 years of data collection (2008-2011), in terms of each child's individually assessed singing ability (based on their singing behavior of two well-known songs to create a "normalized singing score") and their written responses to a specially-designed questionnaire that included a set of statements related to children's sense of being socially included to which the children indicated their level of agreement on a seven-point Likert scale. Data analyses suggested that the higher the normalized singing development rating, the more positive the child's self-concept and sense of being socially included, irrespective of singer age, sex and ethnicity. PMID- 25120517 TI - Intersubjectivity and interaction as crucial for understanding the moral role of shame: a critique of TOSCA-based shame research. PMID- 25120515 TI - The body and the fading away of abstract concepts and words: a sign language analysis. AB - One of the most important challenges for embodied and grounded theories of cognition concerns the representation of abstract concepts, such as "freedom." Many embodied theories of abstract concepts have been proposed. Some proposals stress the similarities between concrete and abstract concepts showing that they are both grounded in perception and action system while other emphasize their difference favoring a multiple representation view. An influential view proposes that abstract concepts are mapped to concrete ones through metaphors. Furthermore, some theories underline the fact that abstract concepts are grounded in specific contents, as situations, introspective states, emotions. These approaches are not necessarily mutually exclusive, since it is possible that they can account for different subsets of abstract concepts and words. One novel and fruitful way to understand the way in which abstract concepts are represented is to analyze how sign languages encode concepts into signs. In the present paper we will discuss these theoretical issues mostly relying on examples taken from Italian Sign Language (LIS, Lingua dei Segni Italiana), the visual-gestural language used within the Italian Deaf community. We will verify whether and to what extent LIS signs provide evidence favoring the different theories of abstract concepts. In analyzing signs we will distinguish between direct forms of involvement of the body and forms in which concepts are grounded differently, for example relying on linguistic experience. In dealing with the LIS evidence, we will consider the possibility that different abstract concepts are represented using different levels of embodiment. The collected evidence will help us to discuss whether a unitary embodied theory of abstract concepts is possible or whether the different theoretical proposals can account for different aspects of their representation. PMID- 25120516 TI - On the interrelation between reduced lateralization, schizotypy, and creativity. PMID- 25120513 TI - Hits and misses: leveraging tDCS to advance cognitive research. AB - The popularity of non-invasive brain stimulation techniques in basic, commercial, and applied settings grew tremendously over the last decade. Here, we focus on one popular neurostimulation method: transcranial direct current stimulation (tDCS). Many assumptions regarding the outcomes of tDCS are based on the results of stimulating motor cortex. For instance, the primary motor cortex is predictably suppressed by cathodal tDCS or made more excitable by anodal tDCS. However, wide-ranging studies testing cognition provide more complex and sometimes paradoxical results that challenge this heuristic. Here, we first summarize successful efforts in applying tDCS to cognitive questions, with a focus on working memory (WM). These recent findings indicate that tDCS can result in cognitive task improvement or impairment regardless of stimulation site or direction of current flow. We then report WM and response inhibition studies that failed to replicate and/or extend previously reported effects. From these opposing outcomes, we present a series of factors to consider that are intended to facilitate future use of tDCS when applied to cognitive questions. In short, common pitfalls include testing too few participants, using insufficiently challenging tasks, using heterogeneous participant populations, and including poorly motivated participants. Furthermore, the poorly understood underlying mechanism for long-lasting tDCS effects make it likely that other important factors predict responses. In conclusion, we argue that although tDCS can be used experimentally to understand brain function its greatest potential may be in applied or translational research. PMID- 25120518 TI - Role-play facilitates children's mindreading of those with atypical color perception. AB - The present study examined the effects of role-play experience on children's mindreading ability. Forty-one primary school children (20 boys, 21 girls, mean age: 9.37 years, range: 8-11 years) were introduced to a communication task in which the use of mindreading was essential. During each trial, participants viewed a shelf, presented on a laptop, which contained several familiar objects, and they were instructed to touch an object on the shelf following an order issued by a "manager" who stood at the opposite side of the shelf. There were two managers: one was a monkey manager with normal color vision, and the other was a dog manager with restricted color vision. The monkey manager could see all the objects in the same colors as the participants, whereas the dog manager saw some objects in different colors. Participants were required to respond according to the manager's instruction. In the restricted color vision condition, the dog manager saw the colors of objects differently; thus, participants had to work out his intentions, according to his different perspective. In the normal color vision condition, all objects were in the same colors as those seen by the monkey manager. Before the test phase, participants in the role-play group were provided a role-play experience in which they assumed the role of the dog manager with restricted color vision. The experimental data were analyzed using a 2 * 2 mixed design ANOVA (role-play condition * communication partner condition) to examine differences in the error rate. Both main effects and its interaction were significant. According to the post-hoc analyses, participants in the no-role-play condition made significantly more errors in the restricted color vision condition than in the normal color vision condition, whereas no such difference was found among participants in the role-play condition. These results suggest that role play experience could facilitate mindreading of characters with restricted color vision. PMID- 25120519 TI - A fan effect in anaphor processing: effects of multiple distractors. AB - Research suggests that the presence of a non-referent from the same category as the referent interferes with anaphor resolution. In five experiments, the hypothesis that multiple non-referents would produce a cumulative interference effect (i.e., a fan effect) was examined. This hypothesis was supported in Experiments 1A and 1B, with subjects being less accurate and slower to recognize referents (1A) and non-referents (1B) as the number of potential referents increased from two to five. Surprisingly, the number of potential referents led to a decrease in anaphor reading times. The results of Experiments 2A and 2B replicated the probe-recognition results in a completely within-subjects design and ruled out the possibility that a speeded-reading strategy led to the fan effect findings. The results of Experiment 3 provided evidence that subjects were resolving the anaphors. These results suggest that multiple non-referents do produce a cumulative interference effect; however, additional research is necessary to explore the effect on anaphor reading times. PMID- 25120520 TI - Responsibility problems for criminal justice. PMID- 25120522 TI - Movement induced tremor in musicians and non-musicians reflects adaptive brain plasticity. AB - Evidence exists that motor dexterity is associated with a higher tremor amplitude of physiological tremor. Likewise, lower frequencies are associated with motor control. So far only case reports of a higher amplitude of physiological tremor in musicians exist. Moreover, no study has investigated lower frequencies during a finger movement task in musicians who can be regarded as a model of motor expertise. We developed a model and derived three hypotheses which we investigated in this study: (1) Tremor amplitude is higher in the range of physiological tremor and (2) higher for frequency ranges of dystonic tremor in musicians compared to non-musicians; (3) there is no difference in tremor amplitude at frequencies below 4 Hz. We measured tremor during a finger flexion extension movement in 19 musicians (age 26.5 +/- 8.2 years) and 24 age matched non-musicians (age 26.5 +/- 8.7). By using empirical mode decomposition in combination with a Hilbert transform we obtained the instantaneous frequency and amplitude, allowing to compare tremor amplitudes throughout the movement at various frequency ranges. We found a significantly higher tremor amplitude in musicians for physiological tremor and a tendency toward a higher amplitude during most of the movement in the frequency range of 4-8 Hz, which, however, was not significant. No difference was found in the frequency range below 4 Hz for the flexion and for almost the entire extension movement. Our results corroborate findings that the 8-12 Hz oscillatory activity plays a role in motor dexterity. However, our results do not allow for the conclusion that tremor at the frequency range of 4-8 Hz is related to either plasticity induced changes that are beneficial for motor skill development nor to maladaptive changes as, e.g., focal dystonia. PMID- 25120521 TI - The emergence of human prosociality: aligning with others through feelings, concerns, and norms. AB - The fact that humans cooperate with nonkin is something we take for granted, but this is an anomaly in the animal kingdom. Our species' ability to behave prosocially may be based on human-unique psychological mechanisms. We argue here that these mechanisms include the ability to care about the welfare of others (other-regarding concerns), to "feel into" others (empathy), and to understand, adhere to, and enforce social norms (normativity). We consider how these motivational, emotional, and normative substrates of prosociality develop in childhood and emerged in our evolutionary history. Moreover, we suggest that these three mechanisms all serve the critical function of aligning individuals with others: Empathy and other-regarding concerns align individuals with one another, and norms align individuals with their group. Such alignment allows us to engage in the kind of large-scale cooperation seen uniquely in humans. PMID- 25120523 TI - Age-related changes in the temporal dynamics of executive control: a study in 5- and 6-year-old children. AB - Based on the Dual Mechanisms of Control theory (Braver et al., 2007), this study conducted in 5- and 6-year-olds, tested for a possible shift between two modes of control, proactive vs. reactive, which differ in the way goal information is retrieved and maintained in working memory. To this end, we developed a children adapted version of the AX-Continuous-Performance Task (AX-CPT). Twenty-nine 5 year-olds and 28-6-year-olds performed the task in both low and high working memory load conditions (corresponding, respectively, to a short and a long cue probe delay). Analyses suggested that a qualitative change in the mode of control occurs within the 5-year-old group. However, quantitative, more graded changes were also observed both within the 5-year-olds, and between 5 and 6 years of age. These graded changes demonstrated an increasing efficiency in proactive control with age. The increase in working memory load did not impact the type of dynamics of control, but had a detrimental effect on sensitivity to cue information. These findings highlight that the development of the temporal dynamics of control can be characterized by a shift from reactive to proactive control together with a more protracted and gradual improvement in the efficiency of proactive control. Moreover, the question of whether the observed shift in the mode of control is task dependant is debated. PMID- 25120524 TI - AT1 receptor blockade alters nutritional and biometric development in obesity resistant and obesity-prone rats submitted to a high fat diet. AB - Obesity is a chronic metabolic condition with important public health implications associated with numerous co-morbidities including cardiovascular disease, insulin resistance, and hypertension. The renin angiotensin system (RAS), best known for its involvement in cardiovascular control and body fluid homeostasis has, more recently, been implicated in regulation of energy balance. Interference with the RAS (genetically or pharmacologically) has been shown to influence body weight gain. In this study we investigated the effects of systemic AT1 receptor blockade using losartan on ingestive behaviors and weight gain in diet induced obese (DIO) rats. Prior to losartan administration (30 mg/kg/day) body weight gain remained constant within the DIO animals (3.6 +/- 0.3 g/day, n = 8), diet resistant (DR) animals (2.1 +/- 0.6 g/day, n = 8) and in the age-matched chow fed control (CHOW) animals (2.8 +/- 0.3 g/day, n = 8), Losartan administration abolished body weight gain in animals fed a high fat diet (DIO: 0.4 +/- 0.7 g/day, n = 8; and DR: -0.8 +/- 0.3 g/day, n = 8) while chow fed animals continued to gain weight (2.2 +/- 0.3 g/day, n = 8) as they had previously to oral administration of losartan. This decrease in daily body weight gain was accompanied by a decrease in food intake in the HFD fed animals. Following the removal of losartan, both the DIO and DR animals again showed daily increases in body weight gain and food intake which were similar to control values. Our data demonstrate that oral losartan administration attenuates body weight gain in animals fed a HFD whether the animal is obese (DIO) or not DR while having no effect on body weight gain in age-matched chow fed animals suggesting a protective effect of losartan against body weight gain while on a HFD. PMID- 25120525 TI - Colors, colored overlays, and reading skills. AB - In this article, we are concerned with the role of colors in reading written texts. It has been argued that colored overlays applied above written texts positively influence both reading fluency and reading speed. These effects would be particularly evident for those individuals affected by the so called Meares Irlen syndrome, i.e., who experience eyestrain and/or visual distortions - e.g., color, shape, or movement illusions - while reading. This condition would interest the 12-14% of the general population and up to the 46% of the dyslexic population. Thus, colored overlays have been largely employed as a remedy for some aspects of the difficulties in reading experienced by dyslexic individuals, as fluency and speed. Despite the wide use of colored overlays, how they exert their effects has not been made clear yet. Also, according to some researchers, the results supporting the efficacy of colored overlays as a tool for helping readers are at least controversial. Furthermore, the very nature of the Meares Irlen syndrome has been questioned. Here we provide a concise, critical review of the literature. PMID- 25120526 TI - Selectivity in early prosocial behavior. AB - Prosocial behavior requires expenditure of personal resources for the benefit of others, a fact that creates a "problem" when considering the evolution of prosociality. Models that address this problem have been developed, with emphasis typically placed on reciprocity. One model considers the advantages of being selective in terms of one's allocation of prosocial behavior so as to improve the chance that one will be benefitted in return. In this review paper, we first summarize this "partner choice" model and then focus on prosocial development in the preschool years, where we make the case for selective partner choice in early instances of human prosocial behavior. PMID- 25120527 TI - Effects of distraction on memory and cognition: a commentary. AB - This commentary is a review of the findings and ideas reported in the preceding nine articles on the effects of distraction on aspects of cognitive performance. The articles themselves deal with the disruptive effects of distraction on recall of words, objects and events, also on visual processing, category formation and other cognitive tasks. The commentary assesses the part played by "domain general" suppression of distracting information and the "domain-specific" competition arising when tasks and distraction involve very similar material. Some forms of distraction are meaningfully relevant to the ongoing task, and Treisman's (1964) model of selective attention is invoked to provide an account of findings in this area. Finally, individual differences to vulnerability to distraction are discussed; older adults are particularly affected by distracting stimuli although the failure to repress distraction can sometimes prove beneficial to later cognitive performance. PMID- 25120528 TI - In the jungle of time: the concept of identity as a way out. AB - WHAT COULD BE A UNIFYING PRINCIPLE FOR THE MANIFOLD OF TEMPORAL EXPERIENCES: the simultaneity or temporal order of events, the subjective present, the duration of experiences, or the impression of a continuity of time? Furthermore, we time travel to the past visiting in imagination previous experiences in episodic memory, and we also time travel to the future anticipating actions or plans. For such time traveling we divide time into three domains: past, present, and future. What could be an escape out of this "jungle of time" characterized by many different perceptual and conceptual phenomena? The key concept we want to propose is "identity" which is derived from homeostasis as a fundamental biological principle. Within this conceptual frame two modes of identity are distinguished: individual or self-identity required because of homeostatic demands, and object related identity necessary for the reliability and efficiency of neuro-cognitive processing. With this concept of self- and object-identity, the different temporal experiences can be conceptualized within a common frame. Thus, we propose a fundamental biological principle to conceptually unify temporal phenomena on the psychological level. PMID- 25120529 TI - Eye movement measurement in diagnostic assessment of disorders of consciousness. AB - We review the literature to appraise the evidence supporting or disputing the use of eye movement measurement in disorders of consciousness (DOC) with low levels of arousal or awareness, such as minimally conscious state (MCS), vegetative state (VS), and coma for diagnostic and prognostic purposes. We will focus on the effectiveness of each technique in the diagnostic classification of these patients and the gradual trend in research from manual to computerized tracking methods. New tools have become available at clinicians' disposal to assess eye movements with high spatial and temporal fidelity. The close relationship between eye movement generation and organic dysfunction in the brain allows these tools to be applied to the assessment of severe DOC as a unique supplementary toolset. We posit that eye tracking can improve clinical diagnostic precision for DOC, a key component of assessment that often dictates the course of clinical care in DOC patients. We see the emergence of long-term eye-tracking studies with seamless integration of technology in the future to improve the performance of clinical assessment in DOC. PMID- 25120530 TI - Developmental dynamics of radial vulnerability in the cerebral compartments in preterm infants and neonates. AB - The developmental vulnerability of different classes of axonal pathways in preterm white matter is not known. We propose that laminar compartments of the developing cerebral wall serve as spatial framework for axonal growth and evaluate potential of anatomical landmarks for understanding reorganization of the cerebral wall after perinatal lesions. The 3-T MRI (in vivo) and histological analysis were performed in a series of cases ranging from 22 postconceptional weeks to 3 years. For the follow-up scans, three groups of children (control, normotypic, and preterms with lesions) were examined at the term equivalent age and after the first year of life. MRI and histological abnormalities were analyzed in the following compartments: (a) periventricular, with periventricular fiber system; (b) intermediate, with periventricular crossroads, sagittal strata, and centrum semiovale; (c) superficial, composed of gyral white matter, subplate, and cortical plate. Vulnerability of thalamocortical pathways within the crossroads and sagittal strata seems to be characteristic for early preterms, while vulnerability of long association pathways in the centrum semiovale seems to be predominant feature of late preterms. The structural indicator of the lesion of the long association pathways is the loss of delineation between centrum semiovale and subplate remnant, which is possible substrate of the diffuse periventricular leukomalacia. The enhanced difference in MR signal intensity of centrum semiovale and subplate remnant, observed in damaged children after first year, we interpret as structural plasticity of intact short cortico cortical fibers, which grow postnatally through U-zones and enter the cortex through the subplate remnant. Our findings indicate that radial distribution of MRI signal abnormalities in the cerebral compartments may be related to lesion of different classes of axonal pathways and have prognostic value for predicting the likely outcome of prenatal and perinatal lesions. PMID- 25120532 TI - Higher TNF-alpha, IGF-1, and Leptin Levels are Found in Tasters than Non-Tasters. AB - Taste perception is controlled by taste cells that are present in the tongue that produce and secrete various metabolic hormones. Recent studies have demonstrated that taste receptors in tongue, gut, and pancreas are associated with local hormone secretion. The aim of this study was to determine whether there is a link between taste sensitivity and levels of circulating metabolic hormones in humans and whether taste sensitivity is potentially related to peripheral metabolic regulation. Thirty-one subjects were recruited and separated into tasters and non tasters based on their phenol thiocarbamide (PTC) bitter taste test results. Fasting plasma and saliva were collected and levels of hormones and cytokines were assayed. We observed significant differences in both hormone levels and hormone-body mass index (BMI) correlation between tasters and non-tasters. Tasters had higher plasma levels of leptin (p = 0.05), tumor necrosis factor alpha (TNF-alpha) (p = 0.04), and insulin-like growth factor 1 (IGF-1) (p = 0.03). There was also a trend toward increased IGF-1 levels in the saliva of tasters (p = 0.06). We found a positive correlation between plasma levels of glucose and BMI (R = 0.4999, p = 0.04) exclusively in non-tasters. In contrast, plasma C-peptide levels were found to be positively correlated to BMI (R = 0.5563, p = 0.03) in tasters. Saliva TNF-alpha levels were negatively correlated with BMI in tasters (R = -0.5908, p = 0.03). Our findings demonstrate that there are differences in circulating levels of leptin, TNF-alpha, and IGF-1 between tasters and non-tasters. These findings indicate that in addition to the regulation of food consumption, taste perception also appears to be tightly linked to circulating metabolic hormone levels. People with different taste sensitivity may respond differently to the nutrient stimulation. Further work investigating the link between taste perception and peripheral metabolic control could potentially lead to the development of novel therapies for obesity or Type 2 diabetes. PMID- 25120533 TI - Inter-species interconnections in acid mine drainage microbial communities. AB - Metagenomic studies are revolutionizing our understanding of microbes in the biosphere. They have uncovered numerous proteins of unknown function in tens of essentially unstudied lineages that lack cultivated representatives. Notably, few of these microorganisms have been visualized, and even fewer have been described ultra-structurally in their essentially intact, physiologically relevant states. Here, we present cryogenic transmission electron microscope (cryo-TEM) 2D images and 3D tomographic datasets for archaeal species from natural acid mine drainage (AMD) microbial communities. Ultrastructural findings indicate the importance of microbial interconnectedness via a range of mechanisms, including direct cytoplasmic bridges and pervasive pili. The data also suggest a variety of biological structures associated with cell-cell interfaces that lack explanation. Some may play roles in inter-species interactions. Interdependences amongst the archaea may have confounded prior isolation efforts. Overall, the findings underline knowledge gaps related to archaeal cell components and highlight the likely importance of co-evolution in shaping microbial lineages. PMID- 25120531 TI - Estrogens and stem cells in thyroid cancer. AB - Recent discoveries highlight the emerging role of estrogens in the initiation and progression of different malignancies through their interaction with stem cell (SC) compartment. Estrogens play a relevant role especially for those tumors bearing a gender disparity in incidence and aggressiveness, as occurs for most thyroid diseases. Although several experimental lines suggest that estrogens promote thyroid cell proliferation and invasion, their precise contribution in SC compartment still remains unclear. This review underlines the interplay between hormones and thyroid function, which could help to complete the puzzle of gender discrepancy in thyroid malignancies. Defining the association between estrogen receptors' status and signaling pathways by which estrogens exert their effects on thyroid cells is a potential tool that provides important insights in pathogenetic mechanisms of thyroid tumors. PMID- 25120534 TI - Effect of sulfate on low-temperature anaerobic digestion. AB - The effect of sulfate addition on the stability of, and microbial community behavior in, low-temperature anaerobic expanded granular sludge bed-based bioreactors was investigated at 15 degrees C. Efficient bioreactor performance was observed, with chemical oxygen demand (COD) removal efficiencies of >90%, and a mean SO(2-) 4 removal rate of 98.3%. In situ methanogensis appeared unaffected at a COD: SO(2-) 4 influent ratio of 8:1, and subsequently of 3:1, and was impacted marginally only when the COD: SO(2-) 4 ratio was 1:2. Specific methanogenic activity assays indicated a complex set of interactions between sulfate-reducing bacteria (SRB), methanogens and homoacetogenic bacteria. SO(2-) 4 addition resulted in predominantly acetoclastic, rather than hydrogenotrophic, methanogenesis until >600 days of SO(2-) 4-influenced bioreactor operation. Temporal microbial community development was monitored by denaturation gradient gel electrophoresis (DGGE) of 16S rRNA genes. Fluorescence in situ hybridizations (FISH), qPCR and microsensor analysis were combined to investigate the distribution of microbial groups, and particularly SRB and methanogens, along the structure of granular biofilms. qPCR data indicated that sulfidogenic genes were present in methanogenic and sulfidogenic biofilms, indicating the potential for sulfate reduction even in bioreactors not exposed to SO(2-) 4. Although the architecture of methanogenic and sulfidogenic granules was similar, indicating the presence of SRB even in methanogenic systems, FISH with rRNA targets found that the SRB were more abundant in the sulfidogenic biofilms. Methanosaeta species were the predominant, keystone members of the archaeal community, with the complete absence of the Methanosarcina species in the experimental bioreactor by trial conclusion. Microsensor data suggested the ordered distribution of sulfate reduction and sulfide accumulation, even in methanogenic granules. PMID- 25120536 TI - Production of a recombinant vaccine candidate against Burkholderia pseudomallei exploiting the bacterial N-glycosylation machinery. AB - Vaccines developing immune responses toward surface carbohydrates conjugated to proteins are effective in preventing infection and death by bacterial pathogens. Traditional production of these vaccines utilizes complex synthetic chemistry to acquire and conjugate the glycan to a protein. However, glycoproteins produced by bacterial protein glycosylation systems are significantly easier to produce, and could possible be used as vaccine candidates. In this work, we functionally expressed the Burkholderia pseudomallei O polysaccharide (OPS II), the Campylobacter jejuni oligosaccharyltransferase (OTase), and a suitable glycoprotein (AcrA) in a designer E. coli strain with a higher efficiency for production of glycoconjugates. We were able to produce and purify the OPS II-AcrA glycoconjugate, and MS analysis confirmed correct glycan was produced and attached. We observed the attachment of the O-acetylated deoxyhexose directly to the acceptor protein, which expands the range of substrates utilized by the OTase PglB. Injection of the glycoprotein into mice generated an IgG immune response against B. pseudomallei, and this response was partially protective against an intranasal challenge. Our experiments show that bacterial engineered glycoconjugates can be utilized as vaccine candidates against B. pseudomallei. Additionally, our new E. coli strain SDB1 is more efficient in glycoprotein production, and could have additional applications in the future. PMID- 25120537 TI - Identification of a cyclic-di-GMP-modulating response regulator that impacts biofilm formation in a model sulfate reducing bacterium. AB - We surveyed the eight putative cyclic-di-GMP-modulating response regulators (RRs) in Desulfovibrio vulgaris Hildenborough that are predicted to function via two component signaling. Using purified proteins, we examined cyclic-di-GMP (c-di GMP) production or turnover in vitro of all eight proteins. The two RRs containing only GGDEF domains (DVU2067, DVU0636) demonstrated c-di-GMP production activity in vitro. Of the remaining proteins, three RRs with HD-GYP domains (DVU0722, DVUA0086, and DVU2933) were confirmed to be Mn(2+)-dependent phosphodiesterases (PDEs) in vitro and converted c-di-GMP to its linear form, pGpG. DVU0408, containing both c-di-GMP production (GGDEF) and degradation domains (EAL), showed c-di-GMP turnover activity in vitro also with production of pGpG. No c-di-GMP related activity could be assigned to the RR DVU0330, containing a metal-dependent phosphohydrolase HD-OD domain, or to the HD-GYP domain RR, DVU1181. Studies included examining the impact of overexpressed cyclic di-GMP-modulating RRs in the heterologous host E. coli and led to the identification of one RR, DVU0636, with increased cellulose production. Evaluation of a transposon mutant in DVU0636 indicated that the strain was impaired in biofilm formation and demonstrated an altered carbohydrate:protein ratio relative to the D. vulgaris wild type biofilms. However, grown in liquid lactate/sulfate medium, the DVU0636 transposon mutant showed no growth impairment relative to the wild-type strain. Among the eight candidates, only the transposon disruption mutant in the DVU2067 RR presented a growth defect in liquid culture. Our results indicate that, of the two diguanylate cyclases (DGCs) that function as part of two-component signaling, DVU0636 plays an important role in biofilm formation while the function of DVU2067 has pertinence in planktonic growth. PMID- 25120535 TI - Deciphering the role of DC subsets in MCMV infection to better understand immune protection against viral infections. AB - Infection of mice with murine cytomegalovirus (MCMV) recapitulates many physiopathological characteristics of human CMV infection and enables studying the interactions between a virus and its natural host. Dendritic cells (DC) are mononuclear phagocytes linking innate and adaptive immunity which are both necessary for MCMV control. DC are critical for the induction of cellular immunity because they are uniquely efficient for the activation of naive T cells during their first encounter with a pathogen. DC are equipped with a variety of innate immune recognition receptors (I2R2) allowing them to detect pathogens or infections and to engulf molecules, microorganisms or cellular debris. The combinatorial engagement of I2R2 during infections controls DC maturation and shapes their response in terms of cytokine production, activation of natural killer (NK) cells and functional polarization of T cells. Several DC subsets exist which express different arrays of I2R2 and are specialized in distinct functions. The study of MCMV infection helped deciphering the physiological roles of DC subsets and their molecular regulation. It allowed the identification and first in vivo studies of mouse plasmacytoid DC which produce high level of interferons-alpha/beta early after infection. Despite its ability to infect DC and dampen their functions, MCMV induces very robust, efficient and long-lasting CD8 T cell responses. Their priming may rely on the unique ability of uninfected XCR1(+) DC to cross-present engulfed viral antigens and thus to counter MCMV interference with antigen presentation. A balance appears to have been reached during co-evolution, allowing controlled replication of the virus for horizontal spread without pathological consequences for the immunocompetent host. We will discuss the role of the interplay between the virus and DC in setting this balance, and how advancing this knowledge further could help develop better vaccines against other intracellular infectious agents. PMID- 25120538 TI - HTLV-1 and HTLV-2: highly similar viruses with distinct oncogenic properties. AB - HTLV-1 and HTLV-2 share broad similarities in their overall genetic organization and expression pattern, but they differ substantially in their pathogenic properties. This review outlines distinctive features of HTLV-1 and HTLV-2 that might provide clues to explain their distinct clinical outcomes. Differences in the kinetics of viral mRNA expression, functional properties of the regulatory and accessory proteins, and interactions with cellular factors and signal transduction pathways are discussed. PMID- 25120542 TI - Articles from the 15th ICI Meeting in Milan, Italy. PMID- 25120540 TI - Ontogenic, Phenotypic, and Functional Characterization of XCR1(+) Dendritic Cells Leads to a Consistent Classification of Intestinal Dendritic Cells Based on the Expression of XCR1 and SIRPalpha. AB - In the past, lack of lineage markers confounded the classification of dendritic cells (DC) in the intestine and impeded a full understanding of their location and function. We have recently shown that the chemokine receptor XCR1 is a lineage marker for cross-presenting DC in the spleen. Now, we provide evidence that intestinal XCR1(+) DC largely, but not fully, overlap with CD103(+) CD11b(-) DC, the hypothesized correlate of "cross-presenting DC" in the intestine, and are selectively dependent in their development on the transcription factor Batf3. XCR1(+) DC are located in the villi of the lamina propria of the small intestine, the T cell zones of Peyer's patches, and in the T cell zones and sinuses of the draining mesenteric lymph node. Functionally, we could demonstrate for the first time that XCR1(+)/CD103(+) CD11b(-) DC excel in the cross-presentation of orally applied antigen. Together, our data show that XCR1 is a lineage marker for cross presenting DC also in the intestinal immune system. Further, extensive phenotypic analyses reveal that expression of the integrin SIRPalpha consistently demarcates the XCR1(-) DC population. We propose a simplified and consistent classification system for intestinal DC based on the expression of XCR1 and SIRPalpha. PMID- 25120541 TI - Toll-like receptor-4 modulation for cancer immunotherapy. PMID- 25120539 TI - Blowing on embers: commensal microbiota and our immune system. AB - Vertebrates have co-evolved with microorganisms resulting in a symbiotic relationship, which plays an important role in health and disease. Skin and mucosal surfaces are colonized with a diverse population of commensal microbiota, over 1000 species, outnumbering the host cells by 10-fold. In the past 40 years, studies have built on the idea that commensal microbiota is in constant contact with the host immune system and thus influence immune function. Recent studies, focusing on mutualism in the gut, have shown that commensal microbiota seems to play a critical role in the development and homeostasis of the host immune system. In particular, the gut microbiota appears to direct the organization and maturation of lymphoid tissues and acts both locally and systemically to regulate the recruitment, differentiation, and function of innate and adaptive immune cells. While the pace of research in the area of the mucosal-immune interface has certainly intensified over the last 10 years, we are still in the early days of this field. Illuminating the mechanisms of how gut microbes shape host immunity will enhance our understanding of the causes of immune-mediated pathologies and improve the design of next-generation vaccines. This review discusses the recent advances in this field, focusing on the close relationship between the adaptive immune system and commensal microbiota, a constant and abundant source of foreign antigens. PMID- 25120543 TI - SOCS Proteins in Macrophage Polarization and Function. PMID- 25120544 TI - The Intercellular Metabolic Interplay between Tumor and Immune Cells. AB - Functional and effective immune response requires a metabolic rewiring of immune cells to meet their energetic and anabolic demands. Beyond this, the availability of extracellular and intracellular metabolites may serve as metabolic signals interconnecting with cellular signaling events to influence cellular fate and immunological function. As such, tumor microenvironment represents a dramatic example of metabolic derangement, where the highly metabolic demanding tumor cells may compromise the function of some immune cells by competing nutrients (a form of intercellular competition), meanwhile may support the function of other immune cells by forming a metabolic symbiosis (a form of intercellular collaboration). It has been well known that tumor cells harness immune system through information exchanges that are largely attributed to soluble protein factors and intercellular junctions. In this review, we will discuss recent advance on tumor metabolism and immune metabolism, as well as provide examples of metabolic communications between tumor cells and immune system, which may represent a novel mechanism of conveying tumor-immune privilege. PMID- 25120545 TI - Strategies for designing and monitoring malaria vaccines targeting diverse antigens. AB - After more than 50 years of intensive research and development, only one malaria vaccine candidate, "RTS,S," has progressed to Phase 3 clinical trials. Despite only partial efficacy, this candidate is now forecast to become the first licensed malaria vaccine. Hence, more efficacious second-generation malaria vaccines that can significantly reduce transmission are urgently needed. This review will focus on a major obstacle hindering development of effective malaria vaccines: parasite antigenic diversity. Despite extensive genetic diversity in leading candidate antigens, vaccines have been and continue to be formulated using recombinant antigens representing only one or two strains. These vaccine strains represent only a small fraction of the diversity circulating in natural parasite populations, leading to escape of non-vaccine strains and challenging investigators' abilities to measure strain-specific efficacy in vaccine trials. Novel strategies are needed to overcome antigenic diversity in order for vaccine development to succeed. Many studies have now cataloged the global diversity of leading Plasmodium falciparum and Plasmodium vivax vaccine antigens. In this review, we describe how population genetic approaches can be applied to this rich data source to predict the alleles that best represent antigenic diversity, polymorphisms that contribute to it, and to identify key polymorphisms associated with antigenic escape. We also suggest an approach to summarize the known global diversity of a given antigen to predict antigenic diversity, how to select variants that best represent the strains circulating in natural parasite populations and how to investigate the strain-specific efficacy of vaccine trials. Use of these strategies in the design and monitoring of vaccine trials will not only shed light on the contribution of genetic diversity to the antigenic diversity of malaria, but will also maximize the potential of future malaria vaccine candidates. PMID- 25120547 TI - Visualizing T Cell Migration in situ. AB - Mounting a protective immune response is critically dependent on the orchestrated movement of cells within lymphoid tissues. The structure of secondary lymphoid organs regulates immune responses by promoting optimal cell-cell and cell extracellular matrix interactions. Naive T cells are initially activated by antigen presenting cells in secondary lymphoid organs. Following priming, effector T cells migrate to the site of infection to exert their functions. Majority of the effector cells die while a small population of antigen-specific T cells persists as memory cells in distinct anatomical locations. The persistence and location of memory cells in lymphoid and non-lymphoid tissues is critical to protect the host from re-infection. The localization of memory T cells is carefully regulated by several factors including the highly organized secondary lymphoid structure, the cellular expression of chemokine receptors and compartmentalized secretion of their cognate ligands. This balance between the anatomy and the ordered expression of cell surface and soluble proteins regulates the subtle choreography of T cell migration. In recent years, our understanding of cellular dynamics of T cells has been advanced by the development of new imaging techniques allowing in situ visualization of T cell responses. Here, we review the past and more recent studies that have utilized sophisticated imaging technologies to investigate the migration dynamics of naive, effector, and memory T cells. PMID- 25120546 TI - Cancer stem cell immunology: key to understanding tumorigenesis and tumor immune escape? AB - Cancer stem cell (CSC) biology and tumor immunology have shaped our understanding of tumorigenesis. However, we still do not fully understand why tumors can be contained but not eliminated by the immune system and whether rare CSCs are required for tumor propagation. Long latency or recurrence periods have been described for most tumors. Conceptually, this requires a subset of malignant cells which is capable of initiating tumors, but is neither eliminated by immune cells nor able to grow straight into overt tumors. These criteria would be fulfilled by CSCs. Stem cells are pluripotent, immune-privileged, and long living, but depend on specialized niches. Thus, latent tumors may be maintained by a niche-constrained reservoir of long-living CSCs that are exempt from immunosurveillance while niche-independent and more immunogenic daughter cells are constantly eliminated. The small subpopulation of CSCs is often held responsible for tumor initiation, metastasis, and recurrence. Experimentally, this hypothesis was supported by the observation that only this subset can propagate tumors in non-obese diabetic/scid mice, which lack T and B cells. Yet, the concept was challenged when an unexpectedly large proportion of melanoma cells were found to be capable of seeding complex tumors in mice which further lack NK cells. Moreover, the link between stem cell-like properties and tumorigenicity was not sustained in these highly immunodeficient animals. In humans, however, tumor-propagating cells must also escape from immune-mediated destruction. The ability to persist and to initiate neoplastic growth in the presence of immunosurveillance - which would be lost in a maximally immunodeficient animal model - could hence be a decisive criterion for CSCs. Consequently, integrating scientific insight from stem cell biology and tumor immunology to build a new concept of "CSC immunology" may help to reconcile the outlined contradictions and to improve our understanding of tumorigenesis. PMID- 25120548 TI - Loss of Arabidopsis GAUT12/IRX8 causes anther indehiscence and leads to reduced G lignin associated with altered matrix polysaccharide deposition. AB - GAlactUronosylTransferase12 (GAUT12)/IRregular Xylem8 (IRX8) is a putative glycosyltransferase involved in Arabidopsis secondary cell wall biosynthesis. Previous work showed that Arabidopsis irregular xylem8 (irx8) mutants have collapsed xylem due to a reduction in xylan and a lesser reduction in a subfraction of homogalacturonan (HG). We now show that male sterility in the irx8 mutant is due to indehiscent anthers caused by reduced deposition of xylan and lignin in the endothecium cell layer. The reduced lignin content was demonstrated by histochemical lignin staining and pyrolysis Molecular Beam Mass Spectrometry (pyMBMS) and is associated with reduced lignin biosynthesis in irx8 stems. Examination of sequential chemical extracts of stem walls using 2D (13)C-(1)H Heteronuclear Single-Quantum Correlation (HSQC) NMR spectroscopy and antibody based glycome profiling revealed a reduction in G lignin in the 1 M KOH extract and a concomitant loss of xylan, arabinogalactan and pectin epitopes in the ammonium oxalate, sodium carbonate, and 1 M KOH extracts from the irx8 walls compared with wild-type walls. Immunolabeling of stem sections using the monoclonal antibody CCRC-M138 reactive against an unsubstituted xylopentaose epitope revealed a bi-lamellate pattern in wild-type fiber cells and a collapsed bi-layer in irx8 cells, suggesting that at least in fiber cells, GAUT12 participates in the synthesis of a specific layer or type of xylan or helps to provide an architecture framework required for the native xylan deposition pattern. The results support the hypothesis that GAUT12 functions in the synthesis of a structure required for xylan and lignin deposition during secondary cell wall formation. PMID- 25120549 TI - Structural divergence of plant TCTPs. AB - The Translationally Controlled Tumor Protein (TCTP) is a highly conserved protein at the level of sequence, considered to play an essential role in the regulation of growth and development in eukaryotes. However, this function has been inferred from studies in a few model systems, such as mice and mammalian cell lines, Drosophila and Arabidopsis. Thus, the knowledge regarding this protein is far from complete. In the present study bioinformatic analysis showed the presence of one or more TCTP genes per genome in plants with highly conserved signatures and subtle variations at the level of primary structure but with more noticeable differences at the level of predicted three-dimensional structures. These structures show differences in the "pocket" region close to the center of the protein and in its flexible loop domain. In fact, all predictive TCTP structures can be divided into two groups: (1) AtTCTP1-like and (2) CmTCTP-like, based on the predicted structures of an Arabidopsis TCTP and a Cucurbita maxima TCTP; according to this classification we propose that their probable function in plants may be inferred in principle. Thus, different TCTP genes in a single organism may have different functions; additionally, in those species harboring a single TCTP gene this could carry multiple functions. On the other hand, in silico analysis of AtTCTP1-like and CmTCTP-like promoters suggest that these share common motifs but with different abundance, which may underscore differences in their gene expression patterns. Finally, the absence of TCTP genes in most chlorophytes with the exception of Coccomyxa subellipsoidea, indicates that other proteins perform the roles played by TCTP or the pathways regulated by TCTP occur through alternative routes. These findings provide insight into the evolution of this gene family in plants. PMID- 25120551 TI - Programmed cell death (PCD): an essential process of cereal seed development and germination. AB - The life cycle of cereal seeds can be divided into two phases, development and germination, separated by a quiescent period. Seed development and germination require the growth and differentiation of new tissues, but also the ordered disappearance of cells, which takes place by a process of programmed cell death (PCD). For this reason, cereal seeds have become excellent model systems for the study of developmental PCD in plants. At early stages of seed development, maternal tissues such as the nucellus, the pericarp, and the nucellar projections undergo a progressive degeneration by PCD, which allows the remobilization of their cellular contents for nourishing new filial tissues such as the embryo and the endosperm. At a later stage, during seed maturation, the endosperm undergoes PCD, but these cells remain intact in the mature grain and their contents will not be remobilized until germination. Thus, the only tissues that remain alive when seed development is completed are the embryo axis, the scutellum and the aleurone layer. In germinating seeds, both the scutellum and the aleurone layer play essential roles in producing the hydrolytic enzymes for the mobilization of the storage compounds of the starchy endosperm, which serve to support early seedling growth. Once this function is completed, scutellum and aleurone cells undergo PCD; their contents being used to support the growth of the germinated embryo. PCD occurs with tightly controlled spatial-temporal patterns allowing coordinated fluxes of nutrients between the different seed tissues. In this review, we will summarize the current knowledge of the tissues undergoing PCD in developing and germinating cereal seeds, focussing on the biochemical features of the process. The effect of hormones and redox regulation on PCD control will be discussed. PMID- 25120550 TI - Mathematical modeling reveals that metabolic feedback regulation of SnRK1 and hexokinase is sufficient to control sugar homeostasis from energy depletion to full recovery. AB - Sucrose and trehalose-6-phosphate (T6P) are central compounds in the regulation and orchestration of whole plant metabolism, growth, development, and flowering. To evaluate their highly complex and regulatory interaction with the two conserved sugar and energy sensors Snf1-related protein kinase 1 (SnRK1), an AMPK related protein kinase, and hexokinase (Hxk), we developed a kinetic model which demonstrates the subtle metabolic control of sugar homeostasis in a wide range of concentrations without the need for changes in gene expression or protein concentrations. Our model approach is based on a comprehensive set of published metabolite concentrations under various conditions and coupled enzyme kinetics accounting for the role of SnRK1 and Hxk in the sugar and energy homeostasis. This allowed us to investigate interactions between sugar phosphates, such as T6P, which are metabolic inhibitors of SnRK1 and Hxk, and sucrose synthesis during the transition from carbon deficiency to availability. Model simulations and sensitivity analyses indicated that slight changes in SnRK1 activity induced by allosteric effectors may be sufficient to explain a dramatic readjustment of metabolic homeostasis. This may comprise up to 10-fold changes in metabolite concentrations. Further, the Hxk/T6P/SnRK1 interaction implemented in the model supports the interpretation of phenotypic and transcriptomic changes observed in Hxk overexpressing plants. Finally, our approach presents a theoretical framework to kinetically link metabolic networks to underlying regulatory instances. PMID- 25120552 TI - Regulation of cell fate determination in plants. PMID- 25120554 TI - Zn(2+)-dependent surface behavior of diacylglycerol pyrophosphate and its mixtures with phosphatidic acid at different pHs. AB - Diacylglycerol pyrophosphate (DGPP) is a minor lipid that attenuates the phosphatidic acid (PA) signal, and also DGPP itself would be a signaling lipid. Diacylglycerol pyrophosphate is an anionic phospholipid with a pyrophosphate group attached to diacylglycerol that was shown to respond to changes of pH, thus affecting the surface organization of DGPP and their interaction with PA. In this work, we have investigated how the presence of Zn(2+) modulates the surface organization of DGPP and its interaction with PA at acidic and basic pHs. Both lipids formed expanded monolayers at pHs 5 and 8. At pH 5, monolayers formed by DGPP became stiffer when Zn(2+)was added to the subphase, while the surface potential decreased. At this pH, Zn(2+) induced a phase transition from an expanded to a condensed-phase state in monolayers formed by PA. Conversely, at pH 8 the effects induced by the presence of Zn(2+) on the surface behaviors of the pure lipids were smaller. Thus, the interaction of the bivalent cation with both lipids was modulated by pH and by the ionization state of the polar head groups. Mixed monolayers of PA and DGPP showed a non-ideal behavior and were not affected by the presence of Zn(2+) at pH 8. This could be explained considering that when mixed, the lipids formed a closely packed monolayer that could not be further modified by the cation. Our results indicate that DGPP and PA exhibit expanded- and condensed-phase states depending on pH, on the proportion of each lipid in the film and on the presence of Zn(2+). This may have implications for a possible role of DGPP as a signaling lipid molecule. PMID- 25120556 TI - Quality assessment and control of high-throughput sequencing data. PMID- 25120555 TI - Primary analysis of repeat elements of the Asian seabass (Lates calcarifer) transcriptome and genome. AB - As part of our Asian seabass genome project, we are generating an inventory of repeat elements in the genome and transcriptome. The karyotype showed a diploid number of 2n = 24 chromosomes with a variable number of B-chromosomes. The transcriptome and genome of Asian seabass were searched for repetitive elements with experimental and bioinformatics tools. Six different types of repeats constituting 8-14% of the genome were characterized. Repetitive elements were clustered in the pericentromeric heterochromatin of all chromosomes, but some of them were preferentially accumulated in pretelomeric and pericentromeric regions of several chromosomes pairs and have chromosomes specific arrangement. From the dispersed class of fish-specific non-LTR retrotransposon elements Rex1 and MAUI like repeats were analyzed. They were wide-spread both in the genome and transcriptome, accumulated on the pericentromeric and peritelomeric areas of all chromosomes. Every analyzed repeat was represented in the Asian seabass transcriptome, some showed differential expression between the gonads. The other group of repeats analyzed belongs to the rRNA multigene family. FISH signal for 5S rDNA was located on a single pair of chromosomes, whereas that for 18S rDNA was found on two pairs. A BAC-derived contig containing rDNA was sequenced and assembled into a scaffold containing incomplete fragments of 18S rDNA. Their assembly and chromosomal position revealed that this part of Asian seabass genome is extremely rich in repeats containing evolutionarily conserved and novel sequences. In summary, transcriptome assemblies and cDNA data are suitable for the identification of repetitive DNA from unknown genomes and for comparative investigation of conserved elements between teleosts and other vertebrates. PMID- 25120553 TI - Looking at plant cell cycle from the chromatin window. AB - The cell cycle is defined by a series of complex events, finely coordinated through hormonal, developmental and environmental signals, which occur in a unidirectional manner and end up in producing two daughter cells. Accumulating evidence reveals that chromatin is not a static entity throughout the cell cycle. In fact, there are many changes that include nucleosome remodeling, histone modifications, deposition and exchange, among others. Interestingly, it is possible to correlate the occurrence of several of these chromatin-related events with specific processes necessary for cell cycle progression, e.g., licensing of DNA replication origins, the E2F-dependent transcriptional wave in G1, the activation of replication origins in S-phase, the G2-specific transcription of genes required for mitosis or the chromatin packaging occurring in mitosis. Therefore, an emerging view is that chromatin dynamics must be considered as an intrinsic part of cell cycle regulation. In this article, we review the main features of several key chromatin events that occur at defined times throughout the cell cycle and discuss whether they are actually controlling the transit through specific cell cycle stages. PMID- 25120557 TI - Development and in silico evaluation of large-scale metabolite identification methods using functional group detection for metabolomics. AB - Large-scale identification of metabolites is key to elucidating and modeling metabolism at the systems level. Advances in metabolomics technologies, particularly ultra-high resolution mass spectrometry (MS) enable comprehensive and rapid analysis of metabolites. However, a significant barrier to meaningful data interpretation is the identification of a wide range of metabolites including unknowns and the determination of their role(s) in various metabolic networks. Chemoselective (CS) probes to tag metabolite functional groups combined with high mass accuracy provide additional structural constraints for metabolite identification and quantification. We have developed a novel algorithm, Chemically Aware Substructure Search (CASS) that efficiently detects functional groups within existing metabolite databases, allowing for combined molecular formula and functional group (from CS tagging) queries to aid in metabolite identification without a priori knowledge. Analysis of the isomeric compounds in both Human Metabolome Database (HMDB) and KEGG Ligand demonstrated a high percentage of isomeric molecular formulae (43 and 28%, respectively), indicating the necessity for techniques such as CS-tagging. Furthermore, these two databases have only moderate overlap in molecular formulae. Thus, it is prudent to use multiple databases in metabolite assignment, since each major metabolite database represents different portions of metabolism within the biosphere. In silico analysis of various CS-tagging strategies under different conditions for adduct formation demonstrate that combined FT-MS derived molecular formulae and CS tagging can uniquely identify up to 71% of KEGG and 37% of the combined KEGG/HMDB database vs. 41 and 17%, respectively without adduct formation. This difference between database isomer disambiguation highlights the strength of CS-tagging for non-lipid metabolite identification. However, unique identification of complex lipids still needs additional information. PMID- 25120558 TI - Genome and metabolic network of "Candidatus Phaeomarinobacter ectocarpi" Ec32, a new candidate genus of Alphaproteobacteria frequently associated with brown algae. AB - Rhizobiales and related orders of Alphaproteobacteria comprise several genera of nodule-inducing symbiotic bacteria associated with plant roots. Here we describe the genome and the metabolic network of "Candidatus Phaeomarinobacter ectocarpi" Ec32, a member of a new candidate genus closely related to Rhizobiales and found in association with cultures of the filamentous brown algal model Ectocarpus. The "Ca. P. ectocarpi" genome encodes numerous metabolic pathways that may be relevant for this bacterium to interact with algae. Notably, it possesses a large set of glycoside hydrolases and transporters, which may serve to process and assimilate algal metabolites. It also harbors several proteins likely to be involved in the synthesis of algal hormones such as auxins and cytokinins, as well as the vitamins pyridoxine, biotin, and thiamine. As of today, "Ca. P. ectocarpi" has not been successfully cultured, and identical 16S rDNA sequences have been found exclusively associated with Ectocarpus. However, related sequences (>=97% identity) have also been detected free-living and in a Fucus vesiculosus microbiome barcoding project, indicating that the candidate genus "Phaeomarinobacter" may comprise several species, which may colonize different niches. PMID- 25120560 TI - The role of AGG interruptions in fragile X repeat expansions: a twenty-year perspective. AB - In 1994, it was suggested that AGG interruptions affect the stability of the fragile X triplet repeat. Until recently, however, this hypothesis was not explored on a large scale due primarily to the technical difficulty of determining AGG interruption patterns of the two alleles in females. The recent development of a PCR technology that overcomes this difficulty and accurately identifies the number and position of AGGs has led to several studies that examine their influence on repeat stability. Here, we present a historical perspective of relevant studies published during the last 20 years on AGG interruptions and examine those recent publications that have refined risk estimates for repeat instability and full-mutation expansions. PMID- 25120561 TI - HumanViCe: host ceRNA network in virus infected cells in human. AB - Host-virus interaction via host cellular components has been an important field of research in recent times. RNA interference mediated by short interfering RNAs and microRNAs (miRNA), is a widespread anti-viral defense strategy. Importantly, viruses also encode their own miRNAs. In recent times miRNAs were identified as key players in host-virus interaction. Furthermore, viruses were shown to exploit the host miRNA networks to suite their own need. The complex cross-talk between host and viral miRNAs and their cellular and viral targets forms the environment for viral pathogenesis. Apart from protein-coding mRNAs, non-coding RNAs may also be targeted by host or viral miRNAs in virus infected cells, and viruses can exploit the host miRNA mediated gene regulatory network via the competing endogenous RNA effect. A recent report showed that viral U-rich non-coding RNAs called HSUR, expressed in primate virus herpesvirus saimiri (HVS) infected T cells, were able to bind to three host miRNAs, causing significant alteration in cellular level for one of the miRNAs. We have predicted protein coding and non protein-coding targets for viral and human miRNAs in virus infected cells. We identified viral miRNA targets within host non-coding RNA loci from AGO interacting regions in three different virus infected cells. Gene ontology (GO) and pathway enrichment analysis of the genes comprising the ceRNA networks in the virus infected cells revealed enrichment of key cellular signaling pathways related to cell fate decisions and gene transcription, like Notch and Wnt signaling pathways, as well as pathways related to viral entry, replication and virulence. We identified a vast number of non-coding transcripts playing as potential ceRNAs to the immune response associated genes; e.g., APOBEC family genes, in some virus infected cells. All these information are compiled in HumanViCe (http://gyanxet-beta.com/humanvice), a comprehensive database that provides the potential ceRNA networks in virus infected human cells. PMID- 25120559 TI - Endoplasmic reticulum stress in hepatic steatosis and inflammatory bowel diseases. AB - As an adaptive response to the overloading with misfolded proteins in the endoplasmic reticulum (ER), ER stress plays critical roles in maintaining protein homeostasis in the secretory pathway to avoid damage to the host. Such a conserved mechanism is accomplished through three well-orchestrated pathways known collectively as unfolded protein response (UPR). Persistent and pathological ER stress has been implicated in a variety of diseases in metabolic, inflammatory, and malignant conditions. Furthermore, ER stress is directly linked with inflammation through UPR pathways, which modulate transcriptional programs to induce the expression of inflammatory genes. Importantly, the inflammation induced by ER stress is directly responsible for the pathogenesis of metabolic and inflammatory diseases. In this review, we will discuss the potential signaling pathways connecting ER stress with inflammation. We will also depict the interplay between ER stress and inflammation in the pathogenesis of hepatic steatosis, inflammatory bowel diseases and colitis-associated colon cancer. PMID- 25120563 TI - Accelerometer-Based Method for Extracting Respiratory and Cardiac Gating Information for Dual Gating during Nuclear Medicine Imaging. AB - Both respiratory and cardiac motions reduce the quality and consistency of medical imaging specifically in nuclear medicine imaging. Motion artifacts can be eliminated by gating the image acquisition based on the respiratory phase and cardiac contractions throughout the medical imaging procedure. Electrocardiography (ECG), 3-axis accelerometer, and respiration belt data were processed and analyzed from ten healthy volunteers. Seismocardiography (SCG) is a noninvasive accelerometer-based method that measures accelerations caused by respiration and myocardial movements. This study was conducted to investigate the feasibility of the accelerometer-based method in dual gating technique. The SCG provides accelerometer-derived respiratory (ADR) data and accurate information about quiescent phases within the cardiac cycle. The correct information about the status of ventricles and atria helps us to create an improved estimate for quiescent phases within a cardiac cycle. The correlation of ADR signals with the reference respiration belt was investigated using Pearson correlation. High linear correlation was observed between accelerometer-based measurement and reference measurement methods (ECG and Respiration belt). Above all, due to the simplicity of the proposed method, the technique has high potential to be applied in dual gating in clinical cardiac positron emission tomography (PET) to obtain motion-free images in the future. PMID- 25120562 TI - A revised dated phylogeny of the arachnid order Opiliones. AB - Dating the Opiliones tree of life has become an important enterprise for this group of arthropods, due to their ancient origins and important biogeographic implications. To incorporate both methodological innovations in molecular dating as well as new systematic discoveries of harvestman diversity, we conducted total evidence dating on a data set uniting morphological and/or molecular sequence data for 47 Opiliones species, including all four well-known Palaeozoic fossils, to test the placement of both fossils and newly discovered lineages in a single analysis. Furthermore, we investigated node dating with a phylogenomic data set of 24,202 amino acid sites for 14 species of Opiliones, sampling all extant suborders. In this way, we approached molecular dating of basal harvestman phylogeny using different data sets and approaches to assess congruence of divergence time estimates. In spite of the markedly different composition of data sets, our results show congruence across all analyses for age estimates of basal nodes that are well constrained with respect to fossil calibrations (e.g., Opiliones, Palpatores). By contrast, derived nodes that lack fossil calibrations (e.g., the suborders Cyphophthalmi, and Laniatores) have large uncertainty intervals in diversification times, particularly in the total evidence dating analysis, reflecting the dearth of calibration points and undersampling of derived lineages. Total evidence dating consistently produced older median ages than node dating for ingroup nodes, due to the nested placement of multiple Palaeozoic fossils. Our analyses support basal diversification of Opiliones in the Ordovician-Devonian period, corroborating the inferred ancient origins of this arthropod order, and underscore the importance of diversity discovery-both paleontological and neontological-in evolutionary inference. PMID- 25120564 TI - 15-Deoxy- gamma 12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPAR gamma and Reduction in NF- kappa B Activity. AB - Objective. 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA-) induced autoimmune hepatitis in mice. Materials and Methods. In vivo, Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and 15d-PGJ2 (10 MUg or 25 MUg) was administered 1 h before the ConA injection. The histological grade, proinflammatory cytokine levels, and NF-kappaB and PPARgamma activity were determined 6, 12, and 24 h after the ConA injection. In vitro, LO2 cells and RAW264.7 cells were pretreated with 15d-PGJ2 (2 MUM) 1 h before the stimulation with ConA (30 MUg/mL). The NF-kappaB and PPARgamma activity were determined 30 min after the ConA administration. Results. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 15d-PGJ2 activated PPARgamma, blocked the degradation of IkappaBalpha, and inhibited the translocation of NF kappaB into the nucleus. Conclusion. These results indicate that 15d-PGJ2 protects against ConA-induced autoimmune hepatitis by reducing proinflammatory cytokines. This reduction in inflammation may correlate with the activation of PPARgamma and the reduction in NF-kappaB activity. PMID- 25120565 TI - Pathogenesis of chronic urticaria: an overview. AB - The pathogenesis of chronic urticaria is not well delineated and the treatment is palliative as it is not tied to the pathomechanism. The centrality of mast cells and their inappropriate activation and degranulation as the key pathophysiological event are well established. The triggering stimuli and the complexity of effector mechanisms remain speculative. Autoimmune origin of chronic urticaria, albeit controversial, is well documented. Numerical and behavioral alterations in basophils accompanied by changes in signaling molecule expression and function as well as aberrant activation of extrinsic pathway of coagulation are other alternative hypotheses. It is also probable that mast cells are involved in the pathogenesis through mechanisms that extend beyond high affinity IgE receptor stimulation. An increasing recognition of chronic urticaria as an immune mediated inflammatory disorder related to altered cytokine-chemokine network consequent to immune dysregulation resulting from disturbed innate immunity is emerging as yet another pathogenic explanation. It is likely that these different pathomechanisms are interlinked rather than independent cascades, acting either synergistically or sequentially to produce clinical expression of chronic urticaria. Insights into the complexities of pathogenesis may provide an impetus to develop safer, efficacious, and targeted immunomodulators and biological treatment for severe, refractory chronic urticaria. PMID- 25120567 TI - Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS. AB - Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production. PMID- 25120566 TI - Zinc therapy in dermatology: a review. AB - Zinc, both in elemental or in its salt forms, has been used as a therapeutic modality for centuries. Topical preparations like zinc oxide, calamine, or zinc pyrithione have been in use as photoprotecting, soothing agents or as active ingredient of antidandruff shampoos. Its use has expanded manifold over the years for a number of dermatological conditions including infections (leishmaniasis, warts), inflammatory dermatoses (acne vulgaris, rosacea), pigmentary disorders (melasma), and neoplasias (basal cell carcinoma). Although the role of oral zinc is well-established in human zinc deficiency syndromes including acrodermatitis enteropathica, it is only in recent years that importance of zinc as a micronutrient essential for infant growth and development has been recognized. The paper reviews various dermatological uses of zinc. PMID- 25120569 TI - Identification and in vitro antimicrobial susceptibility of Brucella species isolated from human brucellosis. AB - Brucellosis is a world-wide zoonotic disease with a major impact on the public health. Due to the high risk of laboratory acquired infection, limited laboratory investigations were performed on this organism, including detailed identification and susceptibility study. Brucella melitensis is the commonest aetiological agent for human brucellosis in this region. The in vitro susceptibility pattern against selected antimicrobial agents was assessed using E-test. All isolates were noted to be sensitive to all the antimicrobial agents tested except for rifampicin where elevated MIC > 1 MUg/mL was noted in 30 out of 41 isolates tested. PMID- 25120570 TI - Degree and rate of growth discordance in dichorionic twins conceived by in vitro fertilization. AB - Objective. Our objective was to estimate degree and rate of discordant growth and its impact on perinatal outcome in dichorionic twin pregnancies conceived by in vitro fertilization (IVF) compared to those conceived spontaneously. Study Design. Growth discordance was defined as 90th percentiles for the study population. Adverse perinatal outcome was defined as 5-minute Apgar score <7 and/or admission to neonatal intensive care unit. Results. In the total study population of dichorionic twins (176 conceived by IVF and 215 spontaneously), 30% discordant growth represented the 90th percentile. After adjusting for gestational age, discordant twins conceived by IVF or spontaneously were at higher risk for adverse perinatal outcome (hazard ratio 4.4; 95% CI 2.4-8.3, P < 0.0001; hazard ratio 2.5; 95% CI 1.5-4.4, P = 0.001, resp.). Similar rates of 5 minute Apgar score <7, admission to neonatal intensive care unit, and delivery <34 weeks were found between discordant twins conceived by IVF and those conceived spontaneously. Conclusion. Dichorionic twins conceived by IVF are at similar risk for the rate and degree of discordant growth and adverse perinatal outcome compared to dichorionic twins conceived spontaneously. PMID- 25120571 TI - Stem cells: innovations in clinical applications. AB - The use of mesenchymal stem cells (MSCs) as clinical therapeutics is a relatively new avenue of study for treatment of a variety of diseases. The therapeutic impact of the MSCs is based upon their multiplicities of function and interaction with host tissues. MSCs can be anti-inflammatory, antifibrotic, antimicrobial, and regenerative, all which may improve outcomes in scenarios of damaged tissues and inflammation. Although most studies focus on utilizing MSCs to direct clinical efficacy, it is the ability to orchestrate host response in surrounding tissue that is especially unique and versatile. This orchestration of host response can be applied to a variety of clinical scenarios not only through cell cell interactions but also through production of bioactive secreted factors. These bioactive factors include small proteins, chemokines, cytokines, and other cellular regulators. These factors have the capacity to induce angiogenesis or blood vessel development, be chemotactic, and induce cellular recruitment. MSCs also have the capacity to differentiate with the implicated environment to regenerate tissue or accommodate host tissue in a cell specific manner. The differentiation cannot only be done in vivo but also can be optimized in vitro prior to in vivo administration, potentiating the versatility of the MSCs and opening avenues for corrective therapy and cell delivery of genes. The differentiation process depends on the environment with which the MSCs are put and results in active communication between the newly administered cells host tissue. Since these properties have been identified, there are a variety of clinical trials and studies being conducted on MSCs ability to treat human disease. This review outlines the potential use of MSCs, the types of tissue, and the innovative applications of MSCs for the treatment of diseases. PMID- 25120572 TI - Clinical, Molecular, and Epidemiological Analysis of Dengue Cases during a Major Outbreak in the Midwest Region of Minas Gerais, Brazil. AB - This study aims to perform the first molecular and clinical-epidemiological analysis of dengue cases in Divinopolis, MG, Brazil. Data from 4,110 cases of dengue were accessed and 190 clinical samples were collected for molecular analyses. In this study, 2.7% of the men and 3.0% of the women were admitted to hospital. There was no association between gender and hospital admission. The symptoms observed in this study are according to the Health Ministry, but fever was present in 82.2% and not in 100% of cases. The chance of hospital admission was 1.55 higher in patients with any kind of bleeding (334) and 2.4% of individuals without bleeding were also hospitalized due to other warning signs. In the molecular analyses, 23% of the samples were positive for DENV. DENV-2 and DENV-3 were identified in 2010, DENV-3 in 2011, DENV-1 in 2012, and DENV-1 and DENV-4 in 2013. DENV detection was possible in samples with only one day of symptoms. This first report of dengue data in Divinopolis provided more insight into the viral types and effects of disease in the city, confirming the need for caution in assessing cases of suspected dengue and for revision of the criteria proposed by the Health Ministry to classify cases of the disease. PMID- 25120573 TI - Ginsenoside rb1 protects neonatal rat cardiomyocytes from hypoxia/ischemia induced apoptosis and inhibits activation of the mitochondrial apoptotic pathway. AB - Aim. To investigate the effect of Ginsenoside Rb1 (GS-Rb1) on hypoxia/ischemia (H/I) injury in cardiomyocytes in vitro and the mitochondrial apoptotic pathway mediated mechanism. Methods. Neonatal rat cardiomyocytes (NRCMs) for the H/I groups were kept in DMEM without glucose and serum, and were placed into a hypoxic jar for 24 h. GS-Rb1 at concentrations from 2.5 to 40 uM was given during hypoxic period for 24 h. NRCMs injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. Cell apoptosis, ROS accumulation, and mitochondrial membrane potential (MMP) were assessed by flow cytometry. Cytosolic translocation of mitochondrial cytochrome c and Bcl-2 family proteins were determined by Western blot. Caspase-3 and caspase-9 activities were determined by the assay kit. Results. GS-Rb1 significantly reduced cell death and LDH leakage induced by H/I. It also reduced H/I induced NRCMs apoptosis induced by H/I, in accordance with a minimal reactive oxygen species (ROS) burst. Moreover, GS-Rb1 markedly decreased the translocation of cytochrome c from the mitochondria to the cytosol, increased the Bcl-2/ Bax ratio, and preserved mitochondrial transmembrane potential (DeltaPsim). Its administration also inhibited activities of caspase-9 and caspase-3. Conclusion. Administration of GS-Rb1 during H/I in vitro is involved in cardioprotection by inhibiting apoptosis, which may be due to inhibition of the mitochondrial apoptotic pathway. PMID- 25120574 TI - Effect of yoga on pain, brain-derived neurotrophic factor, and serotonin in premenopausal women with chronic low back pain. AB - Background. Serotonin and brain-derived neurotrophic factor (BDNF) are known to be modulators of nociception. However, pain-related connection between yoga and those neuromodulators has not been investigated. Therefore, we aimed to evaluate the effect of yoga on pain, BDNF, and serotonin. Methods. Premenopausal women with chronic low back pain practiced yoga three times a week for 12 weeks. At baseline and after 12 weeks, back pain intensity was measured using visual analogue scale (VAS), and serum BDNF and serotonin levels were evaluated. Additionally, back flexibility and level of depression were assessed. Results. After 12-week yoga, VAS decreased in the yoga group (P < 0.001), whereas it increased (P < 0.05) in the control group. Back flexibility was improved in the yoga group (P < 0.01). Serum BDNF increased in the yoga group (P < 0.01), whereas it tended to decrease in the control group (P = 0.05). Serum serotonin maintained in the yoga group, while it reduced (P < 0.01) in the control group. The depression level maintained in the yoga group, whereas it tended to increase in the control group (P = 0.07). Conclusions. We propose that BDNF may be one of the key factors mediating beneficial effects of yoga on chronic low back pain. PMID- 25120576 TI - Tanshinone IIA Downregulates HMGB1 and TLR4 Expression in a Spinal Nerve Ligation Model of Neuropathic Pain. AB - Fifty-four Sprague-Dawley rats weighing 200~240 g were randomly divided into sham operated group (sham group), vehicle-treated SNL group (model group), and Tan IIA treated SNL group (Tan IIA group). Tan IIA was administered intraperitoneally to rats in the Tan IIA-treated group at a dose of 30 mg/kg daily for 14 days after SNL surgery. Paw withdrawal mechanical thresholds (PWTs) and paw withdrawal thermal latencies (PWLs) were measured. High-mobility group box 1 (HMGB1) and Toll-like Receptor 4 (TLR4) mRNA and protein expression in the spinal cord were measured. Tumour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL 1beta), and interleukin-10 (IL-10) in the spinal cord were measured, too. Both the mechanical and heat pain thresholds were significantly decreased. After Tan IIA treatment, HMGB1, and TLR4 mRNA and protein levels, the expression of TNF alpha and IF-1beta was reduced significantly. In conclusion, Tanshinone IIA reversed SNL-induced thermal hyperalgesia and mechanical allodynia and downregulated HMGB1 and TLR4 levels and inhibited the HMGB1-TLR4 pathway. Tanshinone IIA inhibited TNF-alpha and IL-1beta expression but not IF-10 expression in the spinal cords of SNL rats. These results indicate that Tanshinone IIA inhibited SNL-induced neuropathic pain via multiple effects, and targeting the HMGB1-TLR4 pathway could serve as the basis of new antinociceptive agents. PMID- 25120575 TI - Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair. AB - Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC. PMID- 25120577 TI - A Study on the Effect of Neurogenesis and Regulation of GSK3beta/PP2A Expression in Acupuncture Treatment of Neural Functional Damage Caused by Focal Ischemia in MCAO Rats. AB - 170 SD rats were randomly divided to five groups. Rats in model group, no acupuncture group, and acupuncture group were subjected to MCAO surgery. Acupuncture group received 3 consecutive acupuncture treatments at a parameter that deep in 2 mm towards apex nasi and thrust/lifted at 3 times per second for 1 minute, while model group and no-acupuncture group were no-intervention control groups. Serious neural functional damage and sharp decrease of cerebral blood flow, obvious infarction volume, increased nestin mRNA expression, and immunopositive cells population (nestin(+), BrdU(+) and nestin/BrdU(+)) were found in MCAO rats which had not been observed in normal group and sham-operated group. However, the damage was attenuated by rat's "self-healing" capacity 3 days after MCAO. And the "self-healing" capacity can be strengthen by acupuncture treatment through increasing cerebral blood flow, neurogenesis, and regulation of gene transcription or GSK-3beta and PP2A expression. In conclusion, the present study indicates that the underlying mechanism of acupuncture treatment on neural functional damage caused by focal ischemia injury is a multiple interaction which may involve improved cerebral blood supply, neurogenesis, and regulation of gene transcription or GSK-3beta and PP2A expression in MCAO rats. PMID- 25120579 TI - Influence of providers and nurses on completion of non-targeted HIV screening in an urgent care setting. AB - INTRODUCTION: Despite recommendations by the Centers for Disease Control (CDC) that all adults be offered non-targeted HIV screening in all care settings, screening in acute-care settings remains unacceptably low. We performed an observational study to evaluate an HIV screening pilot in an academic-community partnership health center urgent care clinic. METHODS: We collected visit data via encounter forms and demographic and laboratory data from electronic medical records. A post-pilot survey of perceptions of HIV screening was administered to providers and nurses. Multivariable analysis was used to identify factors associated with completion of testing. RESULTS: Visit provider and triage nurse were highly associated with both acceptance of screening and completion of testing, as were younger age, male gender, and race/ethnicity. 23.5% of patients completed tests, although 36.0% requested screening; time constraints as well as risk perceptions by both the provider and patient were cited as limiting completion of screening. Post-pilot surveys showed mixed support for ongoing HIV screening in this setting by providers and little support by nurses. CONCLUSIONS: Visit provider and triage nurse were strongly associated with acceptance of testing, which may reflect variable opinions of HIV screening in this setting by clinical staff. Among patients accepting screening, visit provider remained strongly associated with completion of testing. Despite longstanding recommendations for non-targeted HIV screening, further changes to improve the testing and results process, as well as provider education and buy-in, are needed to improve screening rates. PMID- 25120580 TI - Therapeutic drug monitoring of voriconazole: a case report of multiple drug interactions in a patient with an increased CYP2C19 activity. AB - BACKGROUND: Voriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP 3A4. Drug-drug interactions and genetic polymorphisms modulate their activities. CASE PRESENTATION: A 35-year old African female patient with resistant HIV and a cerebral mass of unknown origin was treated with voriconazole for a suspicion of disseminated Aspergillosis infection. Voriconazole trough concentrations (C0) were within target range while the patient was under esomeprazole, a CYP2C19 inhibitor. Phenotyping showed decreased CYP2C19 activity, whereas genotyping showed a variant allele associated with increased enzyme activity. The patient was switched to ranitidine because of the introduction of atazanavir. CYP3A4 inhibition by atazanavir combined with uninhibited CYP2C19 activity resulted in subtherapeutic voriconazole C0. The reintroduction of esomeprazole allowed restoring voriconazole C0 back to target range. CONCLUSION: The integration of drug-drug interactions and pharmacogenetics data is crucial to interpret drug concentrations correctly, thus preventing suboptimal exposure to voriconazole. PMID- 25120581 TI - The radiographic method for evaluation of axial vertebral rotation - presentation of the new method. AB - The objective of this study is to present a new radiographic method for the assessment of vertebral rotation from an antero-posterior view of conventional X rays which is sufficiently precise in comparison with radiographic methods presently used in clinical practice (methods of Nash-Moe and Perdriolle). This method is based on the properties of the geometric shape of vertebrae and their shared dimensional proportions. It means that the relation between vertebral body width and height doesn't change significantly within the entire thoracic and lumbar sections of the spine. In order to verify the method, we have constructed a special device for vertebral fixation. Subsequently, the X-ray pictures of individual human vertebrae with predefined rotation values (ranging from 0 degrees to 45 degrees by steps of 3 degrees) were radio-graphically measured and then compared with their actual axial rotation on the vertebral rotation device. All arithmetic averages correlate very closely with the actual values. The verification of axial vertebral rotation with the assistance of CT and MRI pictures of six scoliotic patients (in supine position) and the evaluation of axial vertebral rotation by both the new radiographic method and with the Perdriolle method proved the satisfactory accuracy of our method. The main advantage of the newly presented radiographic method is the uncomplicated measurement of vertebral rotation from AP projection of conventional X-ray pictures or from its printed copies. The gold standard of the new radiographic method is the evaluation of axial rotation of vertebrae to 30 degrees approximately and the shape of vertebral bodies without severe structural deformities. The new radiographic method seems to be suitable for use in clinical practice. PMID- 25120578 TI - Differential glycosylation of envelope gp120 is associated with differential recognition of HIV-1 by virus-specific antibodies and cell infection. AB - BACKGROUND: HIV-1 entry into host cells is mediated by interactions between the virus envelope glycoprotein (gp120/gp41) and host-cell receptors. N-glycans represent approximately 50% of the molecular mass of gp120 and serve as potential antigenic determinants and/or as a shield against immune recognition. We previously reported that N-glycosylation of recombinant gp120 varied, depending on the producer cells, and the glycosylation variability affected gp120 recognition by serum antibodies from persons infected with HIV-1 subtype B. However, the impact of gp120 differential glycosylation on recognition by broadly neutralizing monoclonal antibodies or by polyclonal antibodies of individuals infected with other HIV-1 subtypes is unknown. METHODS: Recombinant multimerizing gp120 antigens were expressed in different cells, HEK 293T, T-cell, rhabdomyosarcoma, hepatocellular carcinoma, and Chinese hamster ovary cell lines. Binding of broadly neutralizing monoclonal antibodies and polyclonal antibodies from sera of subtype A/C HIV-1-infected subjects with individual gp120 glycoforms was assessed by ELISA. In addition, immunodetection was performed using Western and dot blot assays. Recombinant gp120 glycoforms were tested for inhibition of infection of reporter cells by SF162 and YU.2 Env-pseudotyped R5 viruses. RESULTS: We demonstrated, using ELISA, that gp120 glycans sterically adjacent to the V3 loop only moderately contribute to differential recognition of a short apex motif GPGRA and GPGR by monoclonal antibodies F425 B4e8 and 447-52D, respectively. The binding of antibodies recognizing longer peptide motifs overlapping with GPGR epitope (268 D4, 257 D4, 19b) was significantly altered. Recognition of gp120 glycoforms by monoclonal antibodies specific for other than V3-loop epitopes was significantly affected by cell types used for gp120 expression. These epitopes included CD4-binding site (VRC03, VRC01, b12), discontinuous epitope involving V1/V2 loop with the associated glycans (PG9, PG16), and an epitope including V3-base-, N332 oligomannose-, and surrounding glycans-containing epitope (PGT 121). Moreover, the different gp120 glycoforms variably inhibited HIV-1 infection of reporter cells. CONCLUSION: Our data support the hypothesis that the glycosylation machinery of different cells shapes gp120 glycosylation and, consequently, impacts envelope recognition by specific antibodies as well as the interaction of HIV-1 gp120 with cellular receptors. These findings underscore the importance of selection of appropriately glycosylated HIV-1 envelope as a vaccine antigen. PMID- 25120582 TI - Human Mammary Tumor Virus (HMTV) sequences in human milk. AB - BACKGROUND: Retroviral sequences 90-95% homologous to the mouse mammary tumor virus (MMTV) were present in 38% of the breast cancers studied from American women and were not detectable in non-tumor breast tissue from the same patient. The entire proviral structure was described and viral particles were isolated from primary cultures of human breast cancer. This virus was designated as human mammary tumor virus (HMTV). Hormone response elements present in the HMTV Long Terminal-Repeat (LTR) suggest a mechanism for association of HMTV with hormonally responding tissues. In fact, the incidence of HMTV sequences is higher in gestational breast cancers, which are associated with hormonal changes. Milk epithelial cells are also under hormonal regulation and therefore are excellent specimens for HMTV sequence detection. METHODS: The HMTV sequence was studied in milk samples from lactating women recruited with increased risk of breast cancer because they had undergone breast biopsies (Biopsy-Group) and lactating women without breast biopsies (Reference-Group). RESULTS: HMTV-env sequences were detected by PCR in milk of 7.61% of 92 women of the Reference-Group and in 20.55% of 73 women of the Biopsy-Group (p: 0.015). The sequences were 94-98% homologous to MMTV. HMTV-env and HMTV-env/LTR junction sequences were detected in high-speed pellet RNA, implying the presence of HMTV viral particles. PCR assays to detect the murine mitochondrial cytochrome oxidase gene and intracisternal-A-type particle sequences were performed to rule out mouse mitochondrial or genomic DNA contamination. Eight women of the 73 Biopsy-Group participants had breast cancer and the milk of only one of these eight women had HMTV-env sequences. In the remaining 65 women of the Biopsy-Group, under enough clinical suspicion to lead to biopsy, HMTV was detected in 14, nearly three times the number of milks as compared to the Reference-Group (21.54% versus 7.61%; p: 0.016). CONCLUSION: The significance of HMTV in milk from the Reference-Group, the greater frequency in the milk of women who had undergone a breast biopsy and its possible infectivity for infants are important questions under study. The similarity of HMTV to MMTV is striking and suggests one possible avenue for viral transmission in humans. PMID- 25120583 TI - A simple structure-based model for the prediction of HIV-1 co-receptor tropism. AB - BACKGROUND: Human Immunodeficiency Virus 1 enters host cells through interaction of its V3 loop (which is part of the gp120 protein) with the host cell receptor CD4 and one of two co-receptors, namely CCR5 or CXCR4. Entry inhibitors binding the CCR5 co-receptor can prevent viral entry. As these drugs are only available for CCR5-using viruses, accurate prediction of this so-called co-receptor tropism is important in order to ensure an effective personalized therapy. With the development of next-generation sequencing technologies, it is now possible to sequence representative subpopulations of the viral quasispecies. RESULTS: Here we present T-CUP 2.0, a model for predicting co-receptor tropism. Based on our recently published T-CUP model, we developed a more accurate and even faster solution. Similarly to its predecessor, T-CUP 2.0 models co-receptor tropism using information of the electrostatic potential and hydrophobicity of V3-loops. However, extracting this information from a simplified structural vacuum-model leads to more accurate and faster predictions. The area-under-the-ROC-curve (AUC) achieved with T-CUP 2.0 on the training set is 0.968+/-0.005 in a leave-one patient-out cross-validation. When applied to an independent dataset, T-CUP 2.0 has an improved prediction accuracy of around 3% when compared to the original T CUP. CONCLUSIONS: We found that it is possible to model co-receptor tropism in HIV-1 based on a simplified structure-based model of the V3 loop. In this way, genotypic prediction of co-receptor tropism is very accurate, fast and can be applied to large datasets derived from next-generation sequencing technologies. The reduced complexity of the electrostatic modeling makes T-CUP 2.0 independent from third-party software, making it easy to install and use. PMID- 25120586 TI - Correlation study on adiponectin gene SNP45 and long-term oxidative stress in patients with diabetes and carotid atherosclerosis. AB - The aim of the present study was to investigate the correlation between the adiponectin gene single nucleotide polymorphism (SNP)45 T/G and long-term oxidative stress in type II diabetes mellitus (T2DM) patients with carotid atherosclerosis. Patients with T2DM were divided into non-carotid atherosclerosis and carotid atherosclerosis groups, which were then subsequently divided into TT and TG + GG groups according to the adiponectin SNP45 T/G genotypes. Enzyme linked immunosorbent assay, TaqMan probe quantitative polymerase chain reaction (PCR), PCR-TaqMan, color Doppler and other methods were used to determine the adiponectin levels, gene polymorphisms, acquired mitochondrial DNA (mtDNA) A3243G somatic cell mutation rates and the carotid intima-media thickness. The somatic cell mutation rate of acquired mtDNA A3243A/G in the T2DM carotid atherosclerosis group was significantly higher compared with the group without carotid atherosclerosis. In addition, the acquired mtDNA A3243A/G somatic cell mutation rate in the T2DM carotid atherosclerosis group with the adiponectin gene SNP45 TT genotype was significantly lower compared with the SNP45 TG/GG genotype group. T2DM combined with carotid atherosclerosis was associated with long-term oxidative stress. In addition, adiponectin gene SNP45 T/G was associated with increased mtDNA A3243A/G somatic mutation rates in T2DM patients with carotid atherosclerosis. Therefore, adiponectin gene polymorphisms may lead to diabetes atherosclerosis through oxidative stress. PMID- 25120587 TI - Correlation between cystathionine beta-synthase T883C genetic polymorphism and primary hypertension. AB - The present study aimed to investigate the correlation between cystathionine beta synthase (CBS) T833C polymorphisms and primary hypertension. A case-control study was conducted by genotyping the representative variation in 545 hypertensive individuals (aged 49.23+/-7.56 years) and 500 normotensive individuals (aged 49.90+/-10.01 years). The T833C genetic polymorphisms of the CBS enzyme were detected in all subjects by amplification refractory mutation system polymerase chain reaction (PCR) analysis. The CBS T833C polymorphism was successfully genotyped in the general population with a sample size of 1,045 (545+500) individuals. The genotypic and allelic frequency distributions of the CBS T833C polymorphism were not significantly different between the hypertensive and normotensive groups (P>0.05). The CC genotype was significantly different (P<0.05) from the CT and TT genotypes in terms of body mass index (BMI), and the levels of triglycerides (TG) and homocysteine (Hcy). Multiple logistic regression analysis revealed that BMI, total cholesterol (TC) level, smoking, plasma Hcy level and a family history of hypertension were the independent risk factors for hypertension in the population studied. The results indicate that the level of plasma Hcy was a risk factor for hypertension in the population studied. However, the mutation of the CBS T833C gene was not concluded to be an important hereditary factor for influencing the level of plasma Hcy. PMID- 25120585 TI - Summary of the various treatments for osteonecrosis of the femoral head by mechanism: A review. AB - Osteonecrosis of the femoral head (ONFH), also known as femoral head avascular necrosis, is a pathological state with a number of possible etiologies including steroid administration, alcohol abuse, traumatic events, vascular injury and idiopathic origins. ONFH causes a reduction in the vascular supply to the subchondral bone of the femoral head, which results in osteocyte death and the collapse of the articular surface. Treatments for ONFH include non-weight-bearing therapy, physical support, the promotion of osteoclast apoptosis, and the reduction of osteoblast and osteocyte apoptosis. The aim of the present review was to summarize the treatments for ONFH by mechanism from a new perspective and to describe the condition with an emphasis on treatment options. PMID- 25120588 TI - Objective parameters aid the prediction of fistulas in pancreatic surgery. AB - Insufficiency of pancreatic anastomosis with leakage from the pancreatic stump and the development of fistulas account for the majority of surgical complications following pancreatic resection, which are often life threatening. The cause of pancreatic fistulas of the remnant tissue on a molecular level remains unclear. Thus, the aim of the present study was to investigate risk factors associated with postoperative pancreatic fistula (POPF) formation and to define parameters that may predict the resection outcome. Pancreatic resection margins were selected from 31 patients, including 16 individuals without and 15 patients with POPF, to analyze the degree of fibrosis, lipomatous atrophy, inflammatory activity and infiltration. Wound healing factors were assessed by luminex technology using tissue homogenates, while the distribution in situ was assessed using immunohistochemistry. Increased chronic inflammatory infiltration, a higher degree of fibrosis and a reduction in lipomatous atrophy were observed in the samples without anastomotic fistulas. Multiplex analysis of 38 wound healing factors demonstrated significantly higher levels of interleukin (IL)-6, 8 and -12, glucagon-like peptide-1 and matrix metalloproteinase (MMP)-1, -2, -3 and -12 in the group without fistulas, while lower concentrations of IL-10, IL-17 and gastric inhibitory polypeptide were observed. Therefore, the observations of the present study indicated that increased inflammatory infiltration and inflammatory activity, as well as higher concentrations of proinflammatory cytokines and higher MMP levels at the resection margins, predisposed individuals to a lower fistula incidence rate following pancreatic resection. PMID- 25120589 TI - Protective effects of quercetin and hyperoside on renal fibrosis in rats with unilateral ureteral obstruction. AB - Prevention of renal fibrosis is an important therapeutic strategy in the treatment of obstructive nephropathy. The purpose of the present study was to identify whether the combination of two natural plant-derived flavanoids, quercetin and hyperoside (QH), could inhibit renal fibrosis in the model of unilateral ureteral obstruction (UUO) in rats. QH mixtures (1:1) were fed to Wistar rats, and UUO ligation was performed on all the rats with the exception of the sham group. Masson's trichrome staining was used for interstitial fibrosis, while immunohistochemistry and western blot analysis were used to detect the expression of alpha-smooth muscle actin (SMA) and fibronectin (FN). In the QH group, the expression of SMA and FN was significantly lower than that in the untreated UUO group. In addition, QH administration significantly inhibited the SMA and FN expression of mesangial cells induced by interleukin-1beta. Consequently, it was evident that combinational QH therapy prevented UUO-induced renal fibrosis. Based on these findings, the combinatorial intervention of phytomedicine may present an improved treatment strategy for renal fibrotic disease. PMID- 25120590 TI - Lentivirus vector-mediated mitofusin-2 overexpression in rat ovary changes endocrine function and promotes follicular development in vivo. AB - The aim of the present study was to evaluate the expression and effect of rat mitofusin-2 (rMfn2) in the ovaries and other organs in rats. Rat models were developed by the intraovarian microinjection of an rMfn2-overexpressing lentiviral vector. Lenti-green fluorescent protein (GFP)-rMfn2 was microinjected into rat ovaries at a dosage of 2*106 tuberculin units virosome (n=25) and lenti GFP was microinjected as a control (n=25). The expression of rMfn2 in the ovaries and other tissues was observed by fluorescence microscopy on days 7, 15, 30, 45 and 60 after the microinjection (n=5/day from each group). The serum levels of estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined by radioimmunoassay. Western blotting was used for the quantitative analysis of the expression of rMfn2 and the progesterone receptor (PR), estradiol receptor (ER), luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR). The expression of rMfn2 was detected on day 7 after infection, increased with time and was maintained efficiently until day 60. In addition, rMfn2 was highly expressed in the fallopian tubes, uterus, cardiac muscle, liver and kidney, but expressed at a low level in adipose tissue. The serum levels of E2 and P in the model group were significantly increased compared with those in the control group, whereas the FSH and LH levels showed no significant difference between groups. The expression levels of the ER and PR in the model group were higher than those in the control group; however, no significant difference was observed between groups for the expression levels of LHR and FSHR. These findings suggest that the intraovarian microinjection of lenti-GFP-rMfn2 resulted in a significant time-dependent overexpression of rMfn2 in various organs, and that rMfn2 overexpression in rat ovaries changed the endocrine function and promoted follicular development. PMID- 25120584 TI - Current animal models of bladder cancer: Awareness of translatability (Review). AB - Experimental animal models are crucial in the study of biological behavior and pathological development of cancer, and evaluation of the efficacy of novel therapeutic or preventive agents. A variety of animal models that recapitulate human urothelial cell carcinoma have thus far been established and described, while models generated by novel techniques are emerging. At present a number of reviews on animal models of bladder cancer comprise the introduction of one type of method, as opposed to commenting on and comparing all classifications, with the merits of a certain method being explicit but the shortcomings not fully clarified. Thus the aim of the present study was to provide a summary of the currently available animal models of bladder cancer including transplantable (which could be divided into xenogeneic or syngeneic, heterotopic or orthotopic), carcinogen-induced and genetically engineered models in order to introduce their materials and methods and compare their merits as well as focus on the weaknesses, difficulties in operation, associated problems and translational potential of the respective models. Findings of these models would provide information for authors and clinicians to select an appropriate model or to judge relevant preclinical study findings. Pertinent detection methods are therefore briefly introduced and compared. PMID- 25120591 TI - Clinical analysis and etiology of porokeratosis. AB - The present study was performed in order to define the clinical manifestations of porokeratosis, with particular emphasis on genital porokeratosis. A total of 55 cases of porokeratosis were retrospectively reviewed between 2000 and 2007 from Huashan Hospital (Shanghai, China). Out of 55 cases, there were 22 cases of porokeratosis of Mibelli, 17 cases of disseminated superficial actinic porokeratosis (DSAP), 15 cases of disseminated superficial porokeratosis and one case of linear porokeratosis. The ratio of males to females was 39:16. Among them, 12 cases had a family history of porokeratosis. During the five-year follow up period, no malignant transformation was observed and no further aggravation of lesions was detected. The results indicated that the initial region of DSAP in the Chinese population may differ from Caucasians. In combination with other studies, the present study found that genital porokeratosis in the Chinese population is often associated with pruritus. Since no recurrence was observed in cases treated with surgical excision, it was suggested that surgical excision is a viable treatment strategy and should be used for porokeratotic lesions if possible. In addition, regular follow-ups are required, since the aggravation of porokeratosis may cause the development of malignancy transformation. PMID- 25120592 TI - Preclinical humanized mouse model with ectopic ovarian tissues. AB - The aim of the present study was to establish human ovarian stroma within the mouse subcutaneously, in order for the resulting stroma to serve as a useful preclinical tool to study the progression of human ovarian cancer in a humanized ovarian microenvironment. Normal human ovarian tissues were subcutaneously implanted into severe combined immunodeficient (SCID) mice and then the implants were identified by immunohistochemistry. The implants became vascularized and retained their original morphology for about 4 weeks following implantation. Immunohistochemical staining for cytokeratin-7 confirmed the ovarian origin of the epithelial cells. CD34 staining demonstrated human-derived vessels. Positive estrogen receptor and partially-positive progesterone receptor staining indicated the estrogen and progesterone dependence of the implants. Only vascular pericytes expressed alpha-smooth muscle actin, indicating the normal ovarian origin of the xenografts. Human ovarian tissue successfully survived in SCID mice and retained its original properties. This humanized mouse model may be used as preclinical tool to investigate ovarian cancer. PMID- 25120593 TI - MicroRNA expression profile in intrauterine hypoxia-induced pulmonary hypoplasia in rats. AB - Hypoxia is necessary for fetal development; however, excess hypoxia is detrimental. The mechanisms underlying the effects of hypoxia on lung development remain unclear, although important roles of microRNAs (miRNAs) during lung development have recently been established. However, the effect on lung development at an miRNA expression level, following changes in oxygen tension, have not yet been studied. In the present study, pregnant rats were exposed to a fraction of inspired oxygen of 10.5 or 21% for two days on gestation day 19, following which the body weight, lung wet weight, radial alveolar count (RAC) and mean linear intercept (Lm) of the newborn pups were analyzed on postnatal day 1. To define the role of miRNAs during lung development following intrauterine hypoxia exposure, the miRNA expression pattern was profiled using a miRNA microarray. The newborn rats in the hypoxic group exhibited statistically significant decreases in body weight, lung weight and the RAC, as well as a marked increase in the Lm. A total of 69 miRNAs were identified to have significant changes in expression, including 55 upregulated and 14 downregulated miRNAs. Quantitative polymerase chain reaction was used to validate the microarray results of six selected miRNAs. Therefore, the results indicated that late gestation intrauterine hypoxia exposure may cause lung injury and miRNAs may play important roles in this process. PMID- 25120594 TI - Comparison of the radiosensitivities of neurons and glial cells derived from the same rat brain. AB - Non-proliferating cells, such as mature neurons, are generally believed to be more resistant to X-rays than proliferating cells, such as glial and vascular endothelial cells. Therefore, the late adverse effects of radiotherapy on the brain have been attributed to the radiation-induced damage of glial and vascular endothelial cells. However, little is known about the radiosensitivities of neurons and glial cells due to difficulties in culturing these cells, particularly neurons, independently. In the present study, primary dissociated neurons and glial cultures were prepared separately from the hippocampi and cerebrum, respectively, which had been obtained from the same fetal rat on embryonic day 18. X-irradiations of 50 Gy were performed on the cultured neurons and glial cells at 7 and 21 days in vitro (DIV). The cells were fixed at 24 h after irradiation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was then performed to measure the apoptotic indices (AIs). The AIs of non-irradiated and irradiated neurons at 7 DIV were 23.7+/-6.7 and 64.9+/-4.8%, and those at 21 DIV were 52.1+/-17.4 and 44.6+/-12.5%, respectively. The AIs of non-irradiated and irradiated glial cells at 7 DIV were 5.8+/-1.5 and 78.4+/-3.3% and those at 21 DIV were 9.6+/-2.6 and 86.3+/-4.9%, respectively. Glial cells and neurons were radiosensitive at 7 DIV. However, while glial cells were radiosensitive at 21 DIV, neurons were not. PMID- 25120595 TI - Elevated levels of alanine transaminase and triglycerides within normal limits are associated with fatty liver. AB - In the present study, the threshold values of laboratory data for the diagnosis of non-alcoholic fatty liver disease (NAFLD) were investigated. The study enrolled patients who had undergone abdominal ultrasound (US) between April 2013 and August 2013, and for whom laboratory data were available on the same day. NAFLD was diagnosed following observations of a bright liver or hepatorenal echo contrast on the abdominal US scans. Patients were excluded from the study if they had liver diseases or had been prescribed prednisolone or methotrexate. Receiver operating characteristic curves, the Wilcoxon signed-rank test and Fisher's exact probability test were used for data analysis. In total, 80 NAFLD and 94 non-NAFLD patients were enrolled in the study. The threshold levels of alanine aminotransferase (ALT) and triglyceride (TG) for the diagnosis of NAFLD were 19.0 IU/l and 101 mg/dl, respectively. Patients were divided into two groups according to the levels of ALT and TG. Those with ALT levels of >19 IU/l and TG levels of >101 mg/dl were defined as the positive group, while the remaining patients were classified as the negative group. The specificity and positive predictive value using the combined threshold levels of ALT >19 IU/l and TG >101 mg/dl were 80.9 and 75.0%, respectively. Therefore, the results indicated that ALT levels of >19 IU/l or TG levels of >101 mg/dl were useful markers for the screening of NAFLD. However, NAFLD was more strongly suspected in patients with ALT levels of >19 IU/l and TG levels of >101 mg/dl. PMID- 25120596 TI - Long-term follow-up of whole lung lavage in patients with pulmonary alveolar proteinosis. AB - Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by intra alveolar accumulation of lipid and proteinaceous material. While a small subset of patients with PAP spontaneously improve or even undergo disease remission, the majority of patients develop persistent or progressive disease. Numerous therapies have been used to treat PAP over the years; however, at present, whole lung lavage (WLL) remains the gold standard treatment for PAP. In the present study, data were accumulated from a cohort of patients with PAP (n=11) between 2003 and 2011 at the Wuxi People's Hospital Affiliated to Nanjing Medical University. The disease affected males and females with a ratio of 2.7:1 and all the males were current or previous smokers. The disease severity score (DSS) of the patients was mainly distributed in DSS 4 or DSS 5. All the patients underwent WLL at least once, with one patient undergoing WLLs twice and another patient three times. The clinical features, arterial blood gas and pulmonary function of the patients, were assessed prior to and following the lavage. WLL resulted in a significant improvement in symptoms, radiographic features, PaO2, D(A-a)O2 and DLCO in patients with PAP, while pulmonary ventilation function did not significantly improve. WLL appears to be an effective approach for the treatment of PAP and leads to an improvement in survival rate. PMID- 25120597 TI - Helicobacter pylori infection promotes the invasion and metastasis of gastric cancer through increasing the expression of matrix metalloproteinase-1 and matrix metalloproteinase-10. AB - The aim of this study was to investigate the effect and mechanism of Helicobacter pylori infection in the invasion and metastasis of gastric cancer. Specimens from 80 patients with gastric cancer (of which 20 patients had metastatic gastric cancer) and 40 patients with chronic gastritis were included in this study. H. pylori infection was determined by ELISA and the expression of matrix metalloproteinase-1 (MMP-1) and MMP-10 was observed using immunohistochemistry. The correlation between H. pylori infection and the clinical pathological features of gastric cancer was analyzed by SPSS 13.0 software. The protein expression levels of MMP-1 and MMP-10 in MGC-803 cells infected with H. pylori were analyzed using western blotting. H. pylori infection was found in 62 of the 80 patients with gastric cancer and in 13 of the 40 patients with chronic gastritis. In addition, H. pylori infection was correlated with the staging and lymph node metastasis, but not with the gender, age and histological types of patients. H. pylori infection was also significantly correlated with the expression of MMP-1 and MMP-10 (r=0.8718, P<0.05 and r=0.5477, P<0.05, respectively). The expression of MMP-1 and MMP-10 was significantly upregulated following induction by H. pylori infection (P<0.05), with significant effects occurring following infection for 12 and 6 h, respectively. H. pylori infection may promote the invasion and metastasis of gastric cancer by increasing the expression of MMP-1 and MMP-10. PMID- 25120598 TI - DNA methylation of microRNA-375 in impaired glucose tolerance. AB - In the present study, the expression levels and DNA methylation status of microRNA (miRNA)-375 in patients with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were analyzed and the role of DNA methylation of miRNA 375 in the pathogenesis of T2DM was investigated. Compared with the miR-375 levels in patients with normal glucose tolerance (NGT; n=53), the samples from patients with IGT (n=44) exhibited downregulation of miR-375, while those from patients with T2DM (n=54) exhibited upregulation of miR-375 in the plasma. Additionally, the samples from patients with IGT were observed to be hypermethylated compared with those from patients with T2DM and NGT (P=0.042). Analysis of three CpG units (CpG1.2, CpG20 and CpG25.26.27) from 17 CpG sites (between -990 and -1,258 bp, relative to the transcription start site) revealed higher methylation levels in patients with IGT compared with those in patients with NGT (P<0.05). The methylation of two CpG units (CpG1.2 and CpG25.26.27) was higher in patients with IGT than in the patients with T2DM (P<0.05). Thus, the present study demonstrated that the miR-375 promoter was hypermethylated and the levels of miR-375 in the plasma were downregulated in the patients with IGT. DNA hypomethylation may have an important role in the regulation of miR-375 expression and may contribute to the pathogenesis of T2DM. PMID- 25120599 TI - Characteristics and risk factor analysis of 410 cases of tracheobronchial tuberculosis. AB - The present study analyzed the characteristics and risk factors associated with tracheobronchial tuberculosis (TBTB) in 410 patients with TBTB. Retrospective analysis was performed on the clinical features, bronchoscopy performance, bacteriological examination, imaging and treatment of 410 patients who were diagnosed with TBTB using bronchoscopy. Among the 410 patients, 10 patients underwent chest X-ray which revealed two cases of atelectasis, eight cases of patch or spot shadows, three cases of cavity, one case of nodule and one case with no abnormalities. The remaining 400 patients underwent computed tomography chest scans and/or airway reconstruction examinations. Among all the lesion types, the cavity type was found to be the most likely to cause bronchial stenosis or obstruction, with statistically significant differences when compared with the congestion, stenosis or scar lesion types (P<0.01). Moreover, for the cavity type, there were 194 sites of obstruction prior to therapy; however, only 23 sites of obstruction remained following therapy. Furthermore, there were 34 sites without stenosis prior to therapy and 205 sites without stenosis following therapy. The number of sites of obstruction was significantly decreased and the number of sites without stenosis was increased upon therapy. These findings suggest that the cavity type is the most sensitive type to therapy among the five types of TBTB lesion. PMID- 25120601 TI - Diagnosis of the cavo-hepato-atrial pathway in Budd-Chiari syndrome by ultrasonography. AB - The aim of this study was to investigate the ultrasonic features of the cavo hepato-atrial pathway in Budd-Chiari syndrome (BCS), by which blood is drained from the occluded inferior vena cava (IVC) to the right atrium via hepatic veins. Ultrasonograms from 11 patients with BCS with cavo-hepato-atrial pathways were retrospectively studied. Doppler ultrasound was used to observe the direction of the flow and measure the velocity of the blood-draining vessels. Blood flow in the draining vessels and the collaterals was shown as blue, red or bicolored depending on whether the flow direction was away from the transducer, towards the transducer or both. For measurement, the Doppler angle between the axis of the Doppler beam and that of the vein examined was always <60 degrees . Ultrasonography was performed 1-2 weeks prior to digital subtraction angiography (DSA). All patients were confirmed by DSA. Membranous and segmental occlusions of IVCs were observed in seven and four cases, respectively. Blood flow from the IVC reversed to the hepatic/accessory hepatic vein, continued through the dilated intrahepatic collaterals, onward to the other hepatic vein and finally to the right atrium. The majority of the inlets (8/11) of hepatic veins above the occlusion were narrow compared with the dilated distant parts of the lumens. Accelerated blood flow in the inlets was detected in all patients regardless of the luminal diameter. In conclusion, the results from the present study suggest that the unusual cavo-hepato-atrial pathway can be diagnosed reliably by ultrasonography, which may be useful for clinical management. PMID- 25120600 TI - Fistular onion stalk extract exhibits anti-atherosclerotic effects in rats. AB - Fistular onion stalk is used as a traditional herbal medicine, and its extract exhibits certain beneficial effects on cardiovascular disease. In this study, the effects of fistular onion stalk extract on the pathological features, circulating inflammatory cytokines, local renin-angiotensin-aldosterone system (RAAS) and signaling pathway activities were examined using an in vivo model of atherosclerosis. Atherosclerosis of the aorta was induced by loading Sprague Dawley rats with a high-fat diet and vitamin D2. Fistular onion stalk extract administration began five weeks after the induction of atherosclerosis and continued for 12 weeks. Rats treated with fistular onion stalk extract showed a significant reduction in the pathological region compared with the vehicle treated controls. Inhibition of atherosclerosis was associated with preservation of the vascular wall and immune cell infiltration. The extract also reduced the levels of the local inflammatory cytokines interleukin (IL)-1beta, IL-6, monocyte chemoattractant protein-1 and tumor necrosis factor-alpha. Furthermore, the extract downregulated the local activity of the RAAS. In addition, extract treatment inhibited several inflammatory signaling pathways by preventing phosphorylation, including the nuclear factor kappaB, Janus kinase/signal transducers and activators of transcription and mitogen-activated protein kinase pathways. These data indicate that fistular onion stalk extract may be useful for the attenuation of atherosclerosis, and the mechanism includes the regulation of the local inflammatory response. PMID- 25120602 TI - Diagnosis and management of a patient with primary pulmonary diffuse large B-cell lymphoma: A case report and review of the literature. AB - Primary pulmonary lymphoma (PPL) is an uncommon type of non-Hodgkin's lymphoma. The majority of PPLs are of low-grade, mucosa-associated lymphoid tissue type. Primary pulmonary diffuse large B-cell lymphoma (DLBCL) is extremely rare, and prompt diagnosis may be challenging since its clinical symptoms and signs are nonspecific. Although the clinical features, diagnostic procedures, optimal management and prognostic factors of this disease have not yet been well defined, open thoracotomy and chest computed tomography (CT)-guided percutaneous biopsy are the preferred methods used in previous studies. In the present case report, the diagnosis and management of a patient with primary pulmonary DLBCL is reported. A 68-year-old patient was admitted to hospital in May 2013, with complaints of shortness of breath and intermittent wheezing and a cough associated with the production of small amounts of phlegm. Following admission, chest CT scans revealed a mass in the right middle lobe with ground-glass opacities at the lesion margins, as well as air bronchograms in the areas of consolidation. Bronchoscopy was performed and revealed an endobronchial lesion and partial stenosis in the distal end of the middle segment bronchus. Transbronchial needle aspiration (TBNA) of the right hilar lymph node, as well as endobronchial biopsy, was performed. The patient was diagnosed with primary pulmonary DLBCL by subsequent histopathological and immunohistochemical analysis of biopsy specimens collected via TBNA. Following the final diagnosis, standard treatment with CHOP chemotherapy resulted in significant clinical and radiological response and the patient remained in remission 8 months later. These results indicate that TBNA may be an effective method for the diagnosis of primary pulmonary DLBCL. PMID- 25120603 TI - Post-transplant recurrent pericarditis with pericardial tamponade is successfully treated with colchicine: A case report. AB - Recurrent pericarditis is a rare complication following renal transplantation. Colchicine, an inhibitor of microtubule polymerization, has been recommended for the treatment of recurrent acute pericarditis in non-transplant patients and is commonly used for the treatment of gout in transplant patients. However, the use of colchicine for the treatment of recurrent pericarditis in renal transplant patients has rarely been reported. In the present study, a rare case of recurrent pericarditis, manifested as large pericardial effusion and pericardial tamponade within the first year following renal transplantation, was successfully treated with colchicine. Therefore, low-dose colchicine may be a safe and effective option for the treatment of recurrent pericarditis in renal transplant patients. PMID- 25120604 TI - Whole bone marrow cell culture: A convenient protocol for the in vitro expansion of endothelial progenitor cells. AB - The number and function of endothelial progenitor cells (EPCs) may be a predictive factor for the severity and outcome of cardiovascular disease. However, the manipulation of bone marrow mononuclear cell (BMMC) cultures for EPCs is an elaborate and difficult procedure in small experimental animals. The present study aimed to assess the feasibility of whole bone marrow cell (WBMC) culture for expanding EPCs in small experimental animals. C57BL/6 mice (age, 3-4 weeks; weight, 9.47+/-0.76 g) were used as the experimental animals, and WBMCs were isolated from the femora and tibiae and cultured in endothelial cell growth medium-2. A BMMC culture for EPCs was used as a control. EPC growth, phenotype and functions were assessed in vitro and in vivo. The results demonstrated that EPCs were easily obtained from a WBMC culture in vitro. The cells exhibited similar growth and biological characteristics when compared with the EPCs derived from the traditional BMMC culture system. Thus, the cells were able to simultaneously bind to lectin and cause phagocytosis of acetylated-low density lipoproteins. In addition, the cells exhibited high expression levels of cluster of differentiation 34 and fetal liver kinase 1, and possessed similar functional properties to BMMC-derived EPCs, including vascular network formation, proliferation, adhesion and migration abilities in vitro. Thus, WBMC-derived EPCs can improve the outcome of pulmonary vascular disease when transplanted into a monocrotaline-induced pulmonary hypertension mouse model. The results of the present study indicated that the WBMC culture system is a more convenient and effective method of obtaining and expanding EPCs compared with BMMC culture, with the advantage of a simplified procedure. PMID- 25120605 TI - Identification of genes in HepG2 cells that respond to DNA methylation and histone deacetylation inhibitor treatment. AB - Previous studies have demonstrated that epigenetics has an important role in the regulation of gene expression in cancer. Epigenetics is the study of reversible, heritable changes in gene function, which occur independently from changes in the DNA sequence. DNA methylation and histone deacetylation are the two most important epigenetic modifications. DNA methylation was one of the first discovered epigenetic modifications and it may lead to changes in chromatin structure, DNA conformation and DNA stability, thereby controlling gene expression. Sample data on the HepG2 cell line from the Gene Expression Omnibus database under GSE5230 accession number were obtained and GEOquery and the limma package were then used to analyze the data and identify differentially expressed genes using Gene Otology. This was conducted in order to investigate the effect on gene expression of inhibiting DNA methylation and histone deacetylation, and to explore the potential role of epigenetics in the development and treatment of hepatic carcinoma. It was found that inhibition of DNA methylation and histone deacetylation affected not only substance metabolism, but also the immune activity in HepG2 cells. Furthermore, common target sites for transcription factors were identified in the differentially expressed genes. It may be concluded that the inhibition of DNA methylation and histone deacetylation contributes to the treatment of hepatic carcinoma and may provide a novel therapeutic strategy for the treatment of hepatic cancer. PMID- 25120607 TI - A patient with agranulocytosis following the discontinuation of methimazole treatment for 4 months: A case report. AB - Agranulocytosis is a rare and serious adverse effect of antithyroid drugs (ATD), in particular methimazole (MMI), and usually develops within 3 months following the start of uninterrupted ATD treatment. Agranulocytosis may also develop for the first time following interruption and subsequent resumption of the same ATD treatment. In this case report, a 27-year-old female, who was treated for thyrotoxicosis with MMI, developed agranulocytosis following the discontinuation of MMI treatment for four months. To the best of our knowledge, this is the first study to report this. The aim of this report is to increase the awareness of physicians of the onset of agranulocytosis when MMI is discontinued, and to demonstrate that MMI should be used with caution. PMID- 25120606 TI - Prognostic significance of artemin and GFRalpha1 expression in laryngeal squamous cell carcinoma. AB - Artemin (ARTN) has been implicated in the development and progression of several human malignancies. However, the clinical and prognostic significance of ARTN and its receptors has not yet been investigated in human laryngeal squamous cell carcinoma (LSCC). Therefore, in the present study, the protein expression of ARTN and its receptor, namely GFRalpha1, was determined in 76 LSCC and 26 laryngeal polyp tissue samples using immunohistochemistry. Furthermore, the clinicopathological and prognostic significance of ARTN and GFRalpha1 expression was analyzed in patients with LSCC. The results revealed that the expression of ARTN and GFRalpha1 was significantly increased in LSCC compared with polyp tissue samples. Furthermore, the expression of ARTN and GFRalpha1 was positively associated with pTNM stage in LSCC. Kaplan-Meier survival analyses revealed a strong association between the expression of ARTN or GFRalpha1 and the survival of patients with LSCC. Correlation analysis demonstrated that the expression of ARTN was significantly correlated with the expression GFRalpha1. In conclusion, the results demonstrated that ARTN and GFRalpha1 may be useful predictors of disease progression and outcome in patients with LSCC. PMID- 25120608 TI - Iron regulates the expression of ferroportin 1 in the cultured hFOB 1.19 osteoblast cell line. AB - Iron metabolism is tightly regulated in osteoblasts, and ferroportin 1 (FPN1) is the only identified iron exporter in mammals to date. In the present study, the regulation of FNP1 in human osteoblasts was investigated following various iron treatments. The human osteoblast cell line hFOB 1.19 was treated with ferric ammonium citrate (FAC) or desferrioxamine (DFO) of various concentrations. The intracellular iron ion levels were measured using a confocal laser scanning microscope. In addition, the mRNA and protein expression levels of FPN1 were detected by quantitative polymerase chain reaction, western blot analysis and immunofluorescence. The results demonstrated that increasing iron concentrations via FAC treatment increased the expression of FPN1. By contrast, decreasing the iron concentration by DFO treatment decreased FNP1 expression levels. In addition to demonstrating that the FNP1 expression changed according to the iron concentration, the observations indicated that changes in FPN1 expression may contribute to the maintenance of the intracellular iron balance in osteoblasts. PMID- 25120609 TI - Unilateral ovarian and fallopian tube agenesis in an infertile patient with a normal uterus. AB - Congenital agenesis of the unilateral adnexa is a condition that has rarely been described in the literature. The current study presents the case of a 26-year-old female who was admitted to the Department of Gynecology at the Women's Hospital of Zhejiang University (Hangzhou, Zhejiang) for primary infertility. The patient was diagnosed with unilateral ovarian and fallopian tubal agenesis, without malformations of the uterus and urinary tract, during diagnostic laparoscopy and hysteroscopy. A literature review was conducted with the aim of determining the possible causes of these anomalies. However, the etiology of the adnexal anomaly remained unclear, although torsion or congenital defects were the most likely explanation. Therefore, the observations of the present study indicate that contralateral tubal pathologies may contribute to sterility. PMID- 25120610 TI - The effect of the Ras homolog gene family (Rho), member A/Rho associated coiled coil forming protein kinase pathway in atrial fibrosis of type 2 diabetes in rats. AB - Diabetes mellitus promotes atrial structural remodeling, thereby producing atrial arrhythmogenicity. Atrial arrhythmia can substantially increase the risk of premature death. The aim of this study was to investigate the role of Ras homolog gene family, member A (RhoA)/Rho associated coiled-coil forming protein kinase (ROCK) in atrial fibrosis in diabetic hearts, and the effects of fasudil hydrochloride hydrate on atrial fibrosis. An eight-week-old male Sprague-Dawley rat model of type 2 diabetes was established using a high-fat diet combined with streptozotocin [30 mg/kg, once, intraperitoneal (i.p.)]. Animals were randomly divided into three groups: Control rats, untreated diabetic rats that received vehicle, and treated diabetic rats that received Rho kinase inhibitor fasudil hydrochloride hydrate (10 mg/kg/day, i.p., for 14 weeks). The morphological features of atrial fibrosis were observed using Masson staining. The mRNA expression levels of RhoA, ROCK1, ROCK2, type-I and type-III procollagen were assessed with quantitative polymerase chain reaction. The protein levels of RhoA, ROCK1 and ROCK2 were evaluated using western blot analysis. The atria of untreated diabetic rats showed evident atrial fibrosis as compared to the control rats; the mRNA expression levels of RhoA, ROCK1, ROCK2, type-I and type-III procollagen were upregulated; and the protein levels of RhoA, ROCK1 and ROCK2 were increased. The treatment with fasudil hydrochloride hydrate significantly reduced atrial fibrosis, mRNA levels of RhoA, ROCK1, ROCK2, type-I and type-III procollagen, and the protein levels of RhoA, ROCK1 and ROCK2. The results suggested that RhoA/ROCK was involved in atrial fibrosis, and that fasudil hydrochloride hydrate ameliorates atrial fibrosis through the RhoA/ROCK pathway in rats with type 2 diabetes. PMID- 25120611 TI - Calcifying aponeurotic fibroma of the finger in an elderly patient: CT and MRI findings with pathologic correlation. AB - Calcifying aponeurotic fibroma (CAF) is a rare, locally aggressive fibroblastic lesion that occurs predominantly in the distal extremities of children and adolescents. In the present study, a case of pathologically proven CAF arising in the right little finger of a 69-year-old woman is presented. Physical examination revealed a firm, immobile, non-tender mass. Plain radiographs showed a faintly calcified soft tissue mass without bone involvement and computed tomography scans clearly demonstrated the presence of the lesion. Magnetic resonance imaging revealed that the lesion exhibited low to intermediate signal intensity on T1 weighted images and heterogeneous high signal intensity with small foci of low signal intensity on T2-weighted spectral presaturation with inversion recovery images. Contrast-enhanced fat-suppressed T1-weighted images demonstrated intense heterogeneous enhancement throughout the mass. The patient underwent an excisional biopsy. Histologically, the tumor showed a biphasic pattern, composed of a moderately cellular fibromatosis-like component and irregular calcified areas with polygonal epithelioid cells. There has been no evidence of local recurrence four months following surgery. To the best of our knowledge, this case report describes the oldest patient with this condition. PMID- 25120612 TI - Promoter methylation of Raf kinase inhibitory protein: A significant prognostic indicator for patients with gastric adenocarcinoma. AB - DNA methylation has an important role in the development of carcinomas. As a metastasis suppressor gene, Raf kinase inhibitory protein (RKIP) suppresses tumor cell invasion and metastasis. In the present study, the associations between RKIP protein expression and promoter methylation with clinicopathological parameters, prognosis and survival rates in gastric adenocarcinoma were investigated. RKIP protein expression and promoter methylation were measured in 135 cases of surgically resected gastric adenocarcinoma specimens and corresponding normal tissues using immunohistochemistry and methylation-specific polymerase chain reaction, respectively. Kaplan-Meier analyses were performed to analyze the patient survival rate. Prognostic factors were determined using multivariate Cox analysis. RKIP promoter methylation was detected in 48.9% of gastric carcinoma tissues and 5.17% of adjacent tissues (P<0.05). RKIP protein expression was detected in 43.0% of gastric carcinoma tissues and 91.1% of adjacent tissues (P<0.05). The protein expression levels and promoter methylation of RKIP were shown to correlate with pathological staging, Union for International Cancer Control-stage, tumor differentiation and lymph node metastasis (P<0.05). In addition, the protein expression of RKIP in gastric carcinomas was demonstrated to be associated with promoter methylation of RKIP. Survival analysis of gastric carcinoma patients revealed that promoter methylation in RKIP-positive tumors correlated with a significantly shorter survival time when compared with RKIP negative tumors (P=0.0002, using the log-rank test). Using multivariate Cox analysis, promoter methylation of RKIP was shown to be an independent prognostic factor (P=0.033). These results indicated that abnormal promoter methylation of RKIP may be one cause of downregulated RKIP expression. Downregulation of RKIP expression was shown to correlate with the incidence and development of gastric carcinomas. Thus, abnormal promoter methylation of RKIP may be a valuable biomarker for estimating gastric carcinoma prognosis. PMID- 25120613 TI - Lopinavir inhibits insulin signaling by promoting protein tyrosine phosphatase 1B expression. AB - Treatment with antiretroviral therapy, including protease inhibitors (PIs), may result in metabolic side-effects, for example insulin resistance. The aim of the present study was to investigate the mechanism of the dysregulation of insulin signaling by two PIs, lopinavir and darunavir, by analyzing changes in the expression or activity of proteins associated with insulin signaling. 3T3-L1 preadipocytes were pretreated with lopinavir or darunavir for 48 h and then stimulated with insulin for 30 min. The cell lysates were subjected to western blotting with anti-phospho-insulin receptor substrate (IRS) 1, anti-IRS1, anti suppressor of cytokine signaling (SOCS) 1, anti-SOCS3 and anti-protein tyrosine phosphatase (PTP) 1B antibodies and to immunoprecipitation with anti-IRS1 antibody. Translocation of glucose transporter 4 (GLUT4) following treatment with lopinavir or darunavir was observed using immunofluorescence. While GLUT4 was recruited to the cellular membrane in control adipocytes following insulin stimulation, it was diffusely distributed in the cytosol in lopinavir-treated adipocytes. In darunavir-treated adipocytes, GLUT4 was mainly recruited to the cellular membrane, but some GLUT4 remained in the cytosol. After insulin stimulation, IRS1 was tyrosine-phosphorylated to a greater extent in control adipocytes compared with darunavir-treated adipocytes. Tyrosine phosphorylation of IRS1 was inhibited in lopinavir-treated adipocytes. The expression of PTP1B was upregulated in adipocytes pretreated with the PIs, particularly lopinavir, compared with those pretreated with a vehicle control. The degree of regulation in insulin signaling differs between lopinavir and darunavir. One mechanism by which lopinavir regulates insulin signaling is by the promotion of PTP1B expression. PMID- 25120614 TI - Type 2 diabetes mellitus control and atherosclerosis prevention in a non-obese rat model using duodenal-jejunal bypass. AB - Type 2 diabetes mellitus (T2DM) is a prevalent disease worldwide and during its conventional treatment, vascular complications remain unavoidable. Roux-en-Y gastric bypass (GBP) is able to induce the remission of T2DM. However, studies of duodenal-jejunal bypass (DJB), a modified procedure of GBP, are being carried out to investigate its ability to induce the remission of T2DM and protect the aorta from atherosclerosis. The present study aimed to investigate the effect of DJB on the rate of T2DM remission and the prevention of atherosclerosis in the aorta in rats with streptozotocin-induced diabetes without obesity, and to explore the mechanism of DJB in protecting the aorta from atherosclerosis. A T2DM rat model was established with a high-fat diet and low-dose streptozotocin. Surgery was performed to analyze its effects on glucose homeostasis, lipid metabolism, inflammation and pathological changes. Furthermore, changes in c-jun NH2-terminal kinase 1 (JNK1) and inhibitor of kappaB kinase (IKKbeta) genes in the aorta following DJB surgery were examined. Levels of blood glucose, lipids, insulin and tumor necrosis factor (TNF)-alpha were significantly elevated in the T2DM diabetic model compared with the non-diabetic control. A gradual recovery was observed in the DJB group following surgery. Foam cells and atherosclerotic plaques appeared in the ascending aortic tissue in the sham-surgery and T2DM groups, whereas only slight lesions were observed in the DJB group. The expression levels of JNK1 and IKKbeta genes in the aorta were significantly increased in the sham-operated and T2DM groups compared with those in the DJB and normal control groups. The present study demonstrated that DJB caused remission of T2DM without weight loss in non-obese rats. Thus, DJB may delay or prevent the occurrence and development of atherosclerosis in the aorta and this may occur through the JNK1 and nuclear factor kappaB (NF-kappaB) signaling pathways. PMID- 25120615 TI - Protective roles of erythropoiesis-stimulating proteins in chronic heart failure with anemia. AB - Anemia is a common comorbidity in patients with chronic heart failure (CHF) and is frequently treated with erythropoiesis-stimulating proteins (ESPs). Previous studies, however, have been relatively short in duration and have not provided conclusive data on the safety or clinical efficacy of ESP treatment. The aim of this study was to explore the safety and therapeutic effects of ESPs in patients with anemia and CHF. A systematic literature search in EMBASE and MEDLINE from their inception to July 2013 was performed, and clinical studies that evaluated the effects of ESPs among patients with CHF were identified. Randomized clinical trials comparing the effects of ESP treatment with those of placebo treatment or usual care regimes in anemic patients with CHF were included. Nine randomized, controlled trials were identified, comprising 750 patients with CHF and anemia receiving ESP treatment for between three months and one year. ESP treatment had a significantly lower risk of CHF hospitalization [relative risk (RR), 0.47; 95% confidence interval (CI), 0.32-0.70; P=0.0002] and a moderate reduction in mortality risk (RR, 0.68; 95% CI, 0.38-1.19; P=0.18). Treatment with ESPs in patients with symptomatic CHF and anemia resulted in significant improvements in hemoglobin, hematocrit and brain natriuretic peptide levels, as well as exercise capacity, renal function, New York Heart Association class and left ventricular ejection fraction. In conclusion, this study found that treatment with ESPs exerts beneficial effects against CHF and is not associated with a higher mortality rate or adverse effects. These outcomes support the instigation of a trial evaluating the treatment of anemia with ESPs in patients with chronic CHF. PMID- 25120616 TI - Toll-like receptor 4 monoclonal antibody attenuates lipopolysaccharide-induced acute lung injury in mice. AB - Toll-like receptor 4 (TLR4) has an important role in the recognition of lipopolysaccharide (LPS) and in the activation of the inflammatory cascade. In the present study, the effect of TLR4 monoclonal antibody (mAb) on LPS-induced acute lung injury (ALI) was investigated in mice. A total of 45 male BALB/c mice were randomly divided into three groups, namely, the control (group C), sepsis (group S) and pretreatment groups (group P). Mice in group P were intraperitoneally treated with TLR4 mAb 1 h prior to the intraperitoneal administration of LPS. Following treatment with LPS for increasing times periods in groups S and P, the mRNA expression level of TLR4 in the lung tissue and the expression of inflammatory factors in the serum were analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. The degree of pulmonary edema, expressed as (wet weight - dry weight)/wet weight, as well as the lung injury scores, observed using a light microscope, were also analyzed. The results demonstrated that intraperitoneal administration of LPS in mice increased the mRNA expression levels of TLR4, the secretion of inflammatory factors in the serum, the degree of pulmonary edema and the lung injury score in a time-dependent manner. However, pretreatment with TLR4 mAb effectively attenuated the increased mRNA expression of TLR4 and the overproduction of inflammatory factors to correct the pulmonary edema and the elevated lung injury score induced by LPS. Therefore, TLR4 plays a critical role in LPS-induced ALI, and the TLR4 mAb decreases the secretion of inflammatory factors and attenuates the degree of pulmonary edema, thereby protecting the lungs from LPS-induced ALI. PMID- 25120617 TI - Treatment protocols for growth hormone-secreting pituitary adenomas combined with craniofacial fibrous dysplasia: A case report of atypical McCune-Albright syndrome. AB - McCune-Albright syndrome (MAS) is a rare, post-zygotic (non-germline) disorder, characterized by hypersecretory endocrinopathies, fibrous dysplasia of the bone and cafe-au-lait macules. The most common endocrine dysfunction is gonadal hyperfunction; thus, hypersecretion of growth hormones (GHs) as a manifestation of endocrine hyperfunction in MAS is rarely reported. MAS affects both genders, although the majority of cases have been reported in young females. Atypical presentations of MAS, with only one or two of the classic symptoms, have been previously described, but remain particularly challenging due to the lack of a diagnostic phenotype. In patients with atypical MAS, analysis of mutations in the gene of the alpha-subunit of the stimulatory G-protein is limited; thus, diagnosis is based on clinical judgment. In the present study, a male with polyostotic fibrous dysplasia and GH-secreting pituitary adenomas, diagnosed with atypical MAS, was reported. The pituitary adenoma was effectively treated with radiotherapy and the patient underwent surgery for the polyostotic fibrous dysplasia, with marked improvements observed in appearance. PMID- 25120618 TI - Overexpression of netrin-1 increases the expression of tight junction-associated proteins, claudin-5, occludin, and ZO-1, following traumatic brain injury in rats. AB - The function of the blood-brain barrier (BBB) depends on the integrity of tight junction (TJ)-associated proteins. Netrin-1 is known to promote angiogenesis and may also regulate the BBB. To understand the association between netrin-1 and the TJ-associated proteins, the expression levels of proteins involved in maintaining the integrity of the BBB, including netrin-1, claudin-5, occludin and zonula occluden (ZO)-1, were investigated in the present study using quantitative polymerase chain reaction, western blot analysis and immunofluorescence. The aim of the present study was to determine the changes in BBB permeability and whether pZsGreen1-N1 mediated overexpression of netrin-1 increased the expression of the TJ-associated proteins following traumatic brain injury (TBI). The results demonstrated that the levels of mRNA transcription and protein expression of the TJ-associated proteins, claudin-5, occludin and ZO-1, were significantly reduced following TBI. Furthermore, the changes in the expression of these three TJ proteins were consistent with the changes in the BBB permeability, indicating that weakening intercellular junctions leads to BBB opening. The present study also demonstrated that netrin-1 significantly increased the downregulation of claudin-5, occludin and ZO-1 expression levels induced by TBI, which provided a basis for further investigation on the role of netrin-1 in the integrity of TJs and proper functioning of the BBB. PMID- 25120619 TI - Role of cystatin C in renal damage and the optimum cut-off point of renal damage among patients with type 2 diabetes mellitus. AB - The aims of the present study were to evaluate the roles of serum cystatin C (SCysC) and urinary cystatin C (UCysC) in renal function impairment and investigate the optimum cut-off point for renal function impairment among patients with type 2 diabetes mellitus (DM). A total of 742 inpatients and outpatients with type 2 DM (age, 20-75 years) were enrolled in this population based cross-sectional study. The levels of SCysC and UCysC were determined and the odds ratios (ORs) and 95% confidence interval (CIs) of the calculated risk ratios of the different renal damage indicators were obtained. The levels of UCysC, urinary beta2-microglobulin (Ubeta2-MG), urinary albumin (UALB) and SCysC in the renal function impairment groups were observed in the following order: GFR C>GFR-B>GFR-A (P<0.05 or P<0.01). According to the levels of GFR were divided into 4 groups, group GFR-A >= 80ml/min, GFR-B group 50-80 ml/min, group Ccr-C 20 50 ml/min, group GFR-D <20 ml/min. Following adjustment for age and gender, multivariate correlation analysis results revealed that levels of Ubeta2-MG, UCysC and UALB negatively correlated with the glomerular filtration rate (GFR; P<0.05 or P<0.01). In addition, the duration of DM and the levels of SCysC and serum uric acid were shown to positively correlate with the GFR (P<0.05 or P<0.01). ORs for early renal function impairment significantly increased from the DM duration category of four years (OR, 1.74; 95% CI, 1.54-1.92). Receiver operating characteristic analysis demonstrated that the optimum DM cut-off point was four years, in which 60.79% sensitivity and 69.66% specificity were observed. Therefore, UCsyC levels may be used as an efficient indicator for the evaluation of early renal function impairment among patients with type 2 DM. In addition, renal lesions may initially occur in the renal tubule and then form in the renal glomerulus of patients with type 2 DM. PMID- 25120620 TI - Irradiation facilitates the inhibitory effect of the heat shock protein 90 inhibitor NVP-BEP800 on the proliferation of malignant glioblastoma cells through attenuation of the upregulation of heat shock protein 70. AB - The present study aimed to investigate the effect of NVP-BEP800, a novel heat shock protein (Hsp) 90 inhibitor of the 2-aminothieno[2,3-d]pyrimidine class, in combination with radiation on glioblastoma cells. T98G human glioblastoma cells were treated with dimethyl sulfoxide (DMSO), NVP-BEP800, NVP-BEP800 in combination with X-ray irradiation (10 Gy, 20 min), or X-ray irradiation only, and cultured for 40 h. Cell viability was measured upon completion of the treatments. In addition, apoptosis was measured and immunoblot analysis was performed to analyze the expression levels of cellular protein inhibitory kappaB kinase beta (IKKbeta). The combined treatment with NVP-BEP800 and X-ray irradiation resulted in the synergistic destruction of malignant cells. Furthermore, NVP-BEP800 significantly induced apoptosis in the human glioblastoma cells. The immunoblot analysis data indicated that NVP-BEP800 markedly reduced the expression level of IKKbeta. The results also revealed that X-ray irradiation significantly attenuated the increase in the level of Hsp70 in cells treated with NVP-BEP800. Since elevated levels of Hsp70 are associated with drug resistance induced by Hsp90 inhibitors, the effects of X-ray irradiation on Hsp70 levels may be associated with the enhanced effect on cells of the presence of irradiation. The results of the current study suggest that irradiation enhances the inhibitory effect of NVP-BEP800 on the proliferation of malignant glioblastoma cells by downregulating the expression level of cellular signaling protein IKKbeta and attenuating the upregulation of Hsp70 that is induced by NVP-BEP800. PMID- 25120621 TI - Effects of hypoxia-inducible factor-1alpha and matrix metalloproteinase-9 on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis-associated lung injury. AB - The aim of this study was to investigate the effects of hypoxia-inducible factor 1alpha (HIF-1alpha) and matrix metalloproteinase-9 (MMP-9) on alveolar-capillary barrier disruption and lung edema in rat models of severe acute pancreatitis associated lung injury (PALI). A total of 40 male Sprague-Dawley rats were randomly divided into a sham surgery group (n=10) and three PALI groups, in which acute pancreatitis was induced by the retrograde infusion of 5% sodium taurocholate (1 ml/kg). The PALI groups were as follows: i) Untreated PALI group (n=10); ii) 2-methoxyestradiol (2ME2) group (5 mg/kg body mass; n=10); and iii) 2ME2 group (15 mg/kg body mass; n=10). In the two 2ME2 groups, the HIF-1alpha inhibitor 2ME2 was administered intraperitoneally 1 h after the induction of AP. The severity of the pancreatitis was evaluated by the serum amylase levels and pathology. The severity of the lung injury was evaluated by the wet/dry ratio, blood gas analysis and pathology. The alveolar-capillary barrier disruption was assessed by Evans blue dye extravasation. The protein and mRNA expression levels of HIF-1alpha and MMP-9 were studied using enzyme-linked immunosorbent assays (ELISAs), western blot analysis and reverse transcription-polymerase chain reaction. The active tumor necrosis factor-alpha levels were measured using an ELISA. The HIF-1alpha inhibitor 2ME2 attenuated the severity of the pancreatitis and PALI, while the lung edema and alveolar-capillary barrier disruption were significantly ameliorated compared with those in the untreated PALI group. Administration of the higher dose of 2ME2 significantly suppressed the protein expression of MMP-9 in the lung tissues. The results indicate that HIF-1alpha has a major function in alveolar-capillary barrier disruption and lung edema in PALI via a molecular pathway cascade involving MMP-9. Inhibition of HIF-1alpha by 2ME2 attenuates alveolar-capillary barrier disruption and lung edema. Pharmacological blockade of this pathway in patients with PALI may provide a novel therapeutic strategy. PMID- 25120623 TI - Inhibitory effect of gene combination in a mouse model of colon cancer with liver metastasis. AB - The aim of the present study was to establish an animal liver metastasis model with human colon cancer and investigate the inhibitory effect of the wild type (WT) p53 gene combined with thymidine kinase/ganciclovir (TK/GCV) and cytosine deaminase/5-fluorocytosine (CD/5-FC) systems on liver metastasis of colon cancer. A nude mouse liver metastasis model with human colon cancer was established via a spleen cultivation method. A total of 32 nude mice were randomly divided into four groups, each group with eight mice. Group 1 mice received splenic injections of SW480 cells (control group), while group 2 mice were injected with SW480/p53 cells in the spleen. Group 3 mice were administered splenic injections of SW480/TK-CD cells, and GCV and 5-FC were injected into the abdominal cavity. Finally, group 4 mice received splenic injections of SW480/p53 cells mixed in equal proportion with SW480/TK-CD cells, as well as GCV and 5-FC injections in the abdominal cavity. These cells described were constructed in our laboratory and other laboratories. The number of liver metastatic tumors, the liver metastasis rate, conventional pathology, electron microscopy and other indicators in the nude mice of each group were compared and observed. The nude mouse liver metastasis model with human colon cancer was successfully established; the liver metastasis rate of the control group was 100%. The results demonstrated that the rate of liver metastasis in the nude mice in each treatment group decreased, as well as the average number of liver metastatic tumors. Furthermore, the effect of the treatment group with genetic combination (group 4) was the most effective, demonstrating that WTp53 had a synergistic effect with TK/GCV and CD/5-FC. Therefore, the present study successfully established a mouse model of liver metastasis with colon cancer by injecting human colon cancer cells in the spleen. Combined gene therapy was shown to have a synergistic effect, which effectively inhibited the formation of liver metastasis from colon cancer. PMID- 25120622 TI - Quantitative assessment of iron in heart and liver phantoms using dual-energy computed tomography. AB - The aim of the present study was to determine the correlation between dual-energy computed tomography (DECT) Hounsfield units (HU) and iron concentration, as well as the correlation between HU and magnetic resonance imaging (MRI)-derived R2* values, in phantoms of the heart and liver tissue. Phantoms were constructed containing pig heart or liver tissue and varying concentrations of iron (0.1, 5, 10, 15, 20 and 25 mg/ml). The phantoms were then examined by DECT and MRI. Linear regression analysis was used to determine the correlations between HU and iron concentration and HU and R2* values. The HU value of DECT increased with increasing iron concentrations in the liver and heart phantoms in a linear manner. The slope of the HU value change against iron concentration revealed that DeltaH80-140 provided a better discernment of iron concentration as compared with DeltaH100-140. The derived R2 values were all >0.9 for the associations of DECT and MRI measurements with iron concentrations. Therefore, DECT may be used for the determination of iron concentration in the liver and heart tissue, with the results correlating with those obtained with MRI. PMID- 25120624 TI - EBP50 regulates the apoptosis of pancreatic cancer cells by decreasing the expression levels of Bcl-2. AB - Increasing evidence has demonstrated that ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (EBP50) is involved in the malignant transformation of numerous human cancers. The present study investigated the involvement of EBP50 overexpression in the tumorigenicity of pancreatic cancer (PC). The results revealed that overexpression of EBP50 suppressed cell growth, promoted cell apoptosis and arrested G1-to-S phase progression in two human PC cell lines. Overexpression of EBP50 also suppressed B-cell lymphoma 2 (Bcl-2) expression. Furthermore, nude mouse tumor xenograft models were established by the subcutaneous injection of cell lines stably transfected with an EBP50-expressing plasmid. The in vivo data indicated that overexpression of EBP50 inhibited the growth of the PC tumors and induced cell apoptosis. Thus, the present study demonstrated that EBP50 overexpression induces growth inhibition and apoptosis in PC by decreasing Bcl-2 expression. The results suggest that EBP50 may function as a potential tumor suppressor in vivo and in vitro. PMID- 25120625 TI - Gliomatosis cerebri mimicking acute viral encephalitis and with malignant transformation of partial lesions: A case report. AB - Gliomatosis cerebri (GC) is a rare glial neoplasm, characterized by extensive diffuse brain infiltration and relative preservation of the underlying architecture. In the present case report, a patient with type 2 GC, which mimicked the clinicoradiological course of acute viral encephalitis, is presented. A 56-year-old male presented with fever, dizziness, headache and numbness in the right extremities three days prior to admission to hospital. The cerebrospinal fluid (CSF) showed mild pleocytosis. Brain magnetic resonance imaging (MRI) revealed hyperintensity on fluid-attenuated inversion recovery images in the left frontal, temporal, insular lobes and in the left thalamus. No signal enhancement was observed following gadolinium administration. The patient was diagnosed with acute viral encephalitis of unknown cause and received a 10 day course of acyclovir, intravenously. At the follow-up three months later, the patient had personality changes and memory deterioration. The results from the follow-up MRI revealed no remarkable changes. At the follow-up six months after presentation, the patient had expressive aphasia and severe headaches. Subsequently, the patient had two tonic-clonic seizure onsets. The results from the MRI showed an increase in lesion size, more edema around the lesion and irregular enhancement in the left frontal lobe. However, the lesions in the left temporal and insular lobes and in the left thalamus were nearly unchanged. Magnetic resonance spectroscopy (MRS) showed elevated choline (Cho)/creatine (Cr) and Cho/N-acetylaspartate (NAA) ratios, as well as decreased NAA/Cr ratios. Surgery was performed and the neuropathological diagnosis of WHO grade III astrocytoma was confirmed. Thus, it is important to pay attention to the differential diagnoses of GC and acute viral encephalitis in patients who have widespread MRI lesions. A brain biopsy is recommended for a diagnosis in this case. PMID- 25120626 TI - In vitro damage of Candida albicans biofilms by chitosan. AB - With the increasing usage of indwelling medical devices in clinical practice, the frequency of fungal infections has increased, such as that of Candida albicans (C. albicans). Biofilms, a protected niche for microorganisms, are resistant to a range of current antifungal agents. Chitosan is a polyatomic biopolymer with advantageous biocompatibility, biodegradation, nontoxicity and antibacterial properties. To investigate the inhibitory effect of chitosan on biofilms formed by C. albicans, cell viability, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H tetrazolium-5-caboxanilide reduction, and morphological assays, including fluorescence microscopy and scanning electron microscopy (SEM), were employed. As assessed by cell viability assay, chitosan showed significant inhibitory effects on the planktonic cells and the biofilm of C. albicans in a dose-dependent manner. Fluorescence microscopy and SEM assays confirmed that the chitosan treated group showed delayed C. albicans biofilm formation with defect morphological features, due to the inhibitory effects of the vast majority of fungal cell growth. In conclusion, C. albicans biofilms were compromised by the treatment with chitosan, providing an alternative therapeutic strategy against the fungal biofilms in the medical devices. PMID- 25120627 TI - Cryopreserved mouse fetal liver stromal cells treated with mitomycin C are able to support the growth of human embryonic stem cells. AB - An immortalized mouse fetal liver stromal cell line, named KM3, has demonstrated the potential to support the growth and maintenance of human embryonic stem cells (hESCs). In this study, the characteristics of KM3 cells were examined following cryopreservation at -70 degrees C and in liquid nitrogen for 15, 30 and 60 days following treatment with 10 MUg/ml mitomycin C. In addition, whether the KM3 cells were suitable for use as feeder cells to support the growth of hESCs was evaluated. The inhibition of mitosis without cell death was observed when the KM3 cells were treated with 10 MUg/ml mitomycin C for 2 h. The morphology of the KM3 cells cryopreserved in liquid nitrogen for 60 days was not markedly changed, and the cell survival rate was 84.60+/-1.14%. By contrast, the survival rate of the KM3 cells was 66.40+/-2.88% following cryopreservation at -70 degrees C for 60 days; the cells readily detached, were maintained for a shorter time, and had a reduced expression level of basic fibroblast growth factor. hESCs cultured on KM3 cells cryopreserved in liquid nitrogen for 60 days showed the typical bird's nest structure, with clear boundaries and a differentiation rate of 16.33+/-2.08%. The differentiation rate of hESCs cultured on KM3 cells cryopreserved at -70 degrees C for 60 days was 37.67+/-3.51%. These results indicate that the cryopreserved KM3 cells treated with mitomycin C may be directly used in the subculture of hESCs, and the effect is relatively good with -70 degrees C short-term or liquid nitrogen cryopreservation. PMID- 25120628 TI - Nicotinamide mononucleotide improves energy activity and survival rate in an in vitro model of Parkinson's disease. AB - Nicotinamide adenine dinucleotide (NAD+) repletion has been shown to provide marked neuroprotection from genotoxic agent-induced neuronal and astrocyte cell death. One of the key precursors of NAD+ is nicotinamide mononucleotide (NMN). Therefore, it was hypothesized that NMN may attenuate apoptosis and improve energy metabolism in Parkinson's disease (PD)-like behavioral and neuropathological changes, and produce significant beneficial effects. In this study, a cellular model of PD, using rotenone-treated PC12 cells, was established to test the hypothesis that NMN may decrease PD-like pathological changes. Experiments were carried out to investigate cell survival, including an intracellular lactate dehydrogenase (LDH) assay. Apoptotic and necrotic cell death, NAD+ levels and ATP levels were also evaluated. It was observed that NMN was able to significantly attenuate the rotenone-induced reduction in the survival rate of PC12 cells, as assessed by MTT and LDH assays. NMN treatment also significantly reduced the rotenone-induced apoptosis of the cells, as assessed by flow cytometry-based Annexin V/7-aminoactinomycin D staining. Furthermore, NMN restored intracellular levels of NAD+ and ATP in the rotenone treated cells, thus demonstrating the capacity of NMN to ameliorate mitochondrial inhibitor-induced impairments of energy metabolism. The present study indicates that NMN produces significant beneficial effects by attenuating apoptosis and improving energy metabolism in a cellular model of PD. These results suggest that NMN may become a promising therapeutic drug for PD. PMID- 25120629 TI - Associations between apolipoprotein CIII concentrations and microalbuminuria in type 2 diabetes. AB - Microalbuminuria (MAU) is a strong predictor of diabetic nephropathy (DN), which is the main cause of morbidity and mortality in patients with diabetes mellitus (DM). Dyslipidemia exists in the majority of patients with DM and contributes to micro- and macrovascular complications associated with DM. Apolipoprotein CIII (apoCIII) is an inhibitor of the activity of lipoprotein lipase, which metabolizes triglyceride (TG) in very low-density lipoprotein (VLDL) and facilitates its clearance from plasma. The aim of the present study was to investigate the associations between apoCIII and MAU and the effects of atorvastatin in type 2 diabetes. In total, 120 subjects were divided into type 2 diabetes and type 2 DN groups, while 60 healthy subjects were selected as controls. The patients with DN were administered 20 mg atorvastatin daily for 16 weeks. Blood pressure, body mass index (BMI) and levels of HbA1c, FBG, TG, VLDL cholesterol (VLDL-C), apoCIII and MAU were markedly elevated in the type 2 diabetes and type 2 DN groups compared with those in the control group (P<0.01), while high-density lipoprotein-cholesterol (HDL-C) levels were decreased significantly (P<0.01). All patients with type 2 DN showed significantly elevated blood pressure, apoCIII levels, MAU, course of the disease and rate of stroke and retinopathy compared with the patients with type 2 diabetes (P<0.01). MAU was significantly positively correlated with the course of the disease, systolic blood pressure, diastolic blood pressure, BMI and HbA1c, FBG, TG, total cholesterol, low-density lipoprotein-cholesterol, VLDL-C and apoCIII levels (P<0.05), whereas negatively correlated with HDL-C levels (r=-0.194, P=0.020). Logistic regression analysis showed that apoCIII levels were independently associated with MAU (odds ratio, 1.100; 95% confidence interval, 1.037-1.153; P<0.001). Atorvastatin improved the lipid profile and MAU in patients with type 2 DN (P<0.01). Therefore, the present study demonstrated that an independent positive correlation exists between the levels of apoCIII and MAU in patients with type 2 diabetes. Furthermore, atorvastatin may be used to improve the lipid profile and MAU in type 2 DN. PMID- 25120630 TI - Antiosteoporotic effects of Polycan in combination with calcium lactate-gluconate in ovariectomized rats. AB - The aim of the present study was to investigate the optimum composition of Polycan (beta-glucan complex) and calcium lactate-gluconate (CaLG) that exhibited the most beneficial effects in ovariectomy (OVX)-induced osteoporotic rats. Polycan and CaLG single formulas (100 mg/kg each), and three doses (50, 100 and 200 mg/kg) of three mixed formulas [polycan:CaLG (PCLG)=1:99, 5:95 and 10:90] were orally administered once a day for 84 days. The effects of the test materials were compared with those of a risedronate sodium-treated group. OVX resulted in an increase in body weight, decreased bone formation, elevated serum osteocalcin levels and urine deoxypyridinoline/creatinine ratio, as well as decreased serum bone-specific alkaline phosphatase levels, femur indices, bone mineral content, bone mineral density and failure load. However, these OVX induced osteoporotic changes markedly decreased following the administration of the test materials. Continuous oral treatment of Polycan or CaLG single formulas and the PCLG mixed formulas preserved bone mass and strength. The PCLG 10:90 mixed formula exhibited the most favorable synergistic antiosteoporotic effects in the OVX-induced osteoporotic rats as compared with equal doses of the Polycan or CaLG single formulas. PMID- 25120631 TI - Naringin administration inhibits platelet aggregation and release by reducing blood cholesterol levels and the cytosolic free calcium concentration in hyperlipidemic rabbits. AB - This study investigated the effects of naringin on platelet aggregation and release in hyperlipidemic rabbits, and the underlying mechanisms. The safety of naringin was also investigated. The rabbits were orally administered 60, 30 or 15 mg/kg of naringin once a day for 14 days after being fed a high fat/cholesterol diet for four weeks. Following the two weeks of drug administration, the degree of platelet aggregation induced by arachidonic acid, adenosine diphosphate and collagen was significantly reduced by naringin at certain doses compared with those in the rabbits of the model group (P<0.01). The levels of P-selectin and platelet factor 4 (PF4) also decreased following treatment with naringin compared with those of the model group. Certain doses of naringin significantly reduced the total cholesterol (TC) levels and elevated the ratio of high-density lipoprotein cholesterol to TC compared with those in the model group, and significantly decreased the cytosolic free calcium concentration ([Ca2+]i). No significant difference in the coagulation function was observed between the control and drug-treatment groups. These results indicate that naringin improved platelet aggregation and inhibited the excessive release of P-selectin and PF4 in hyperlipidemic rabbits. This study suggests that the antiplatelet effect of naringin may be due to its ability to regulate the levels of blood cholesterol and [Ca2+]i in platelets. Naringin also did not cause bleeding in the hyperlipidemic rabbits. PMID- 25120632 TI - Pharmacological postconditioning with tanshinone IIA attenuates myocardial ischemia-reperfusion injury in rats by activating the phosphatidylinositol 3 kinase pathway. AB - Tanshinone IIA, one of the active ingredients in the Chinese medicine Danshen, is cardioprotective when applied prior to sustained myocardial ischemia. The present study aimed to investigate whether pharmacological postconditioning with tanshinone IIA attenuates myocardial ischemia-reperfusion injury when applied prior to prolonged reperfusion following a sustained ischemia. A total of 88 Sprague-Dawley rats received 30 min myocardial ischemia followed by 5 or 120 min reperfusion. Compared with the ischemia-reperfusion model group, the group that received an intravenous injection of 10 mg/kg tanshinone IIA prior to reperfusion had a reduced myocardial infarct size, higher levels of phospho-Akt and phospho endothelial nitric oxide synthase and less reduction in the optical density of the mitochondria at 540 nm, indicating that the mitochondrial permeability transition (MPT) was attenuated. The cardioprotective effect conferred by tanshinone IIA was abolished by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). These results demonstrate that tanshinone IIA postconditioning protects the myocardium from ischemia-reperfusion injury through the PI3K/Akt pathway, and the MPT may be also involved in this process. PMID- 25120633 TI - Effects of spironolactone and losartan on the early neovascularization of acute myocardial infarction. AB - The aim of the present study was to investigate the effects of spironolactone and losartan on the early healing stage of acute myocardial infarction (AMI) in rats. An AMI rat model was established and the rats were randomly divided into four groups: AMI (n=12), AMI + spironolactone (AMI + S; n=12), AMI + losartan (AMI + L; n=12) and AMI + spironolactone combined with losartan (AMI + S + L; n=12). Sham-operated rats served as a control group (n=12). The expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the non-infarcted myocardium surrounding the AMI area were determined using immunohistochemistry. In addition, the capillary density in the non-infarcted myocardium surrounding the AMI area was detected. The capillary densities around the infarcted area in the AMI and treatment groups at day 7 and 14 following AMI surgery were significantly higher compared with the sham-operated rats. Compared with the AMI group, the capillary densities around the infarcted area and the ratio of MMPs/TIMP-1 were increased in the treatment groups following AMI surgery; however, the increased ratio of MMPs/TIMP-1 was reduced at day 14 following AMI surgery. Therefore, these results indicated that spironolactone and losartan may promote the formation of collateral circulation in the non-infarcted tissue surrounding the infarcted area by regulating the production of MMPs. PMID- 25120635 TI - Autologous stem cell transplantation for a monoclonal gammopathy of undetermined significance mimicking amyotrophic lateral sclerosis: A case report. AB - It is rare for patients with monoclonal gammopathy of undetermined significance (MGUS) to present with clinical features of fatal motor neuron disease, for example amyotrophic lateral sclerosis (ALS). There is no standard and effective therapy for either MGUS or ALS. In addition, stem cell transplantation appears to be ineffective for the treatment of this disease. In the present study, a 47-year old female with MGUS that mimicked ALS is presented. The M-protein levels of the patient were normalized following two cycles of chemotherapy and autologous stem cell transplantation treatment. MGUS was found to be alleviated and the symptoms of ALS did not deteriorate. The results showed a positive therapeutic effect of autologous stem cell transplantation for MGUS. PMID- 25120634 TI - Effect of sodium ferulate on delayed rectifier K+ currents in PC12 cells. AB - In order to investigate the effect of sodium ferulate (SF) on voltage-activated K+ channels, the delayed rectifier K+ current (Ik) in PC12 rat pheochromocytoma cells was recorded using the automated patch-clamp method. The results indicated that following the application of SF, the Ik in PC12 cells was significantly decreased in a concentration-dependent manner. The analysis of activation kinetic curves and inactivation kinetic curves of Ik showed that SF had an effect on the activation and inactivation kinetics. Following the application of 15.3 MUM SF, the activation curve of the Ik of PC12 cells was shifted to positive potentials and the inactivation curve of the Ik of PC12 cells was shifted to negative potentials. This study revealed that the delayed rectifier K+ currents of PC12 cells were inhibited following SF treatment in a concentration-dependent manner. The mechanism may be associated with the delayed activation and enhanced inactivation of Ik-associated channels. PMID- 25120636 TI - Exposure to high levels of glucose increases the expression levels of genes involved in cholesterol biosynthesis in rat islets. AB - Cells continually adjust their gene expression profiles in order to adapt to the availability of nutrients. Glucose is a major regulator of pxancreatic beta-cell function and cell growth. However, the mechanism of beta-cell adaptation to high levels of glucose remains uncertain. To identify the specific targets responsible for adaptation to high levels of glucose, the differentially expressed genes from primary rat islets treated with 3.3 and 16.7 mmol/l glucose for 24 h were detected by DNA microarray. The results revealed that the expression levels of genes that encode enzymes required for de novo cholesterol biosynthesis [3 hydroxy-3-methylglutaryl-CoA synthase 1 (Hmgcs1), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), mevalonate (diphospho) decarboxylase (Mvd), isopentenyl diphosphate delta-isomerase 1 (Idi1), squalene epoxidase (Sqle) and 7 dehydrocholesterol reductase (Dhcr7)] were significantly increased in islets treated with high levels of glucose compared with those in the islets treated with lower glucose levels. Quantitative polymerase chain reaction further confirmed that glucose stimulated the expression levels of these genes in a dose- and time-dependent manner. A similar result was obtained in islets isolated from rats subjected to 12, 24, 48 and 72 h of continuous glucose infusion. It has previously been recognized that cholesterol homeostasis is important for beta cell function. The present study provides, to the best of our knowledge, the first evidence for the involvement of the de novo cholesterol biosynthesis pathway in the adaptation of rat islets to high levels of glucose in vitro and in vivo. PMID- 25120637 TI - Protective effects of Guanxin Shutong capsule drug-containing serum on tumor necrosis factor-alpha-induced endothelial dysfunction through nicotinamide adenine dinucleotide phosphate oxidase and the nitric oxide pathway. AB - The Chinese medicinal formula Guanxin Shutong capsule (GXSTC) has been used for almost 10 years as a clinical treatment for chest pain, depression, palpitation and cardiovascular diseases. The aim of this study was to investigate the effects of GXSTC drug-containing serum on tumor necrosis factor-alpha (TNF-alpha) stimulated endothelial cells. Cell viability was measured by MTT assay, and nitric oxide (NO) levels and NO synthase (NOS) activity were measured as standards of endothelial dysfunction. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were evaluated using commercial kits. In addition, the protein expression of endothelial NOS (eNOS), AKT and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits was examined to evaluate the effect of GXSTC drug-containing serum on ECV304 cells. GXSTC significantly reversed the decrease in NO production induced by TNF-alpha (5 ng/ml) in ECV304 cells. The expression of NADPH oxidase subunits was increased by TNF-alpha treatment, but markedly inhibited by treatment with GXSTC in TNF-alpha-stimulated cells. In summary, GXSTC increased the production of NO in ECV304 cells and exerted a protective effect on ECV304 cells stimulated with TNF-alpha by upregulating the mRNA and protein expression of eNOS. This was accompanied by increased SOD activity and reduced MDA levels. These results suggested that GXSTC protects the endothelium via the NO pathway and exhibits antioxidant effects. PMID- 25120638 TI - Inhibition of Aurora-B suppresses HepG2 cell invasion and migration via the PI3K/Akt/NF-kappaB signaling pathway in vitro. AB - In the present study, the effect of Aurora-B inhibition on HepG2 cell invasion and migration in vitro was investigated. A recombinant plasmid targeting the Aurora-B gene (MiR-Aurora-B) was used to inhibit Aurora-B expression in HepG2 cells. Cell migration and invasion were investigated using Transwell migration and invasion assays. The results demonstrated that cell invasion and migration were suppressed by inhibiting Aurora-B. In addition, the effect of Aurora-B inhibition on the activity of the phosphoinositide 3-kinase (PI3K)/Akt/nuclear factor (NF)-kappaB signaling pathway was investigated by analyzing the protein expression levels of phosphorylated (p)-Akt, Akt, NF-kappaB p65, matrix metalloproteinase (MMP)-2 and MMP-9 using western blot analysis. The results demonstrated that the protein expression levels of p-Akt, NF-kappaB p65, MMP-2 and MMP-9 were reduced significantly by inhibiting Aurora-B. Therefore, inhibition of Aurora-B was shown to suppress hepatocellular carcinoma cell migration and invasion by decreasing the activity of the PI3K/Akt/NF-kappaB signaling pathway in vitro. PMID- 25120639 TI - Progesterone protects blood-brain barrier function and improves neurological outcome following traumatic brain injury in rats. AB - Inflammatory responses are associated with blood-brain barrier (BBB) dysfunction and neurological deficits following traumatic brain injury (TBI). The aim of the present study was to investigate the effects of progesterone on the expression of the inflammatory mediators prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), nuclear factor kappaB (NF-kappaB) and tumor necrosis factor-alpha (TNF-alpha) in the brain, BBB permeability, cerebral edema and neurological outcome, as well as to explore the mechanism of its neuroprotective effect. In this study, male rats were randomly divided into three groups: a sham-operated group (SHAM), a TBI group (TBI) and a progesterone treatment group (TBI-PROG). The TBI model was established using a modified Feeney's weight-dropping method. Brain samples were extracted 24 h following injury. The expression levels of COX-2 and NF-kappaB were examined using immunohistochemistry, whilst the expression levels of PGE2 and TNF-alpha were detected by enzyme-linked immunosorbent assay. BBB permeability was analyzed using Evans blue and cerebral edema was determined using the dry-wet method. The neurological outcome was evaluated using the modified neurological severity score test. The results revealed that progesterone treatment significantly reduced post-injury inflammatory response, brain edema and Evans blue dye extravasation, and improved neurological scores compared with those in the TBI group. In conclusion, the inhibition of inflammation may be an important mechanism by which progesterone protects the BBB and improves neurological outcome. PMID- 25120640 TI - Dendrobium candidum Wall. ex Lindl. attenuates CCl4-induced hepatic damage in imprinting control region mice. AB - The aim of the present study was to determine the preventive effect of the traditional Chinese medicine, Dendrobium candidum Wall ex Lindl. (D. candidum), on CCl4-induced hepatic damage in mice. The CCl4-induced hepatic damage mice were treated with D. candidum, and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglyceride (TG) and total cholesterol (TC) were determined. In addition, serum cytokine levels of interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were analyzed with kits, while liver tissues were analyzed using hematoxylin and eosin staining and reverse transcription polymerase chain reaction (RT-PCR). Furthermore, the contents of D. candidum were determined by nuclear magnetic resonance (NMR). D. candidum was demonstrated to successfully prevent hepatic damage in mice. The serum levels of AST, ALT and LDH were significantly decreased when the mice were treated with 200 and 400 mg/kg D. candidum, as compared with the control mice (P<0.05). The lowest enzymatic activities were exhibited in the 400 mg/kg D. candidum group, which produced similar results to the positive control drug, silymarin. In addition, in the 400 mg/kg D. candidum group, the highest levels of TG and TC were observed among the treated groups. D. candidum-treated groups also demonstrated reduced levels of the serum proinflammatory cytokines, IL-6, IL-12, TNF-alpha and IFN-gamma. The sections of liver tissue examined during histopathology in the high concentration 400 mg/kg D. candidum group recovered well from CCl4 damage; however, the sections in the 200 mg/kg D. candidum group revealed necrosis to a more serious degree. RT-PCR analysis was conducted on inflammation-associated genes, including nuclear factor (NF)-kappaB, IkappaB-alpha, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, in the livers of the mice. The 400 mg/kg D. candidum group demonstrated significantly decreased mRNA expression levels of NF-kappaB, iNOS and COX-2, but an increased expression level of IkappaB-alpha when compared with the CCl4-treated control group. Furthermore, using NMR, 11 compounds were identified in the D. candidum leaf, whose functional contents may aid the preventive effect observed in the current study. Therefore, D. candidum may potentially contribute to the prevention of CCl4-induced hepatic damage in vivo. PMID- 25120641 TI - NUP214 fusion genes in acute leukemia (Review). AB - Nucleoporin 214 (NUP214), previously termed CAN, is required for cell cycle and nucleocytoplasmic transport. The genetic features and clinical implications of five NUP214-associated fusion genes are described in this review. SET-NUP214 was most frequently observed in T-cell acute lymphoblastic leukemia (T-ALL), concomitant with the elevated expression of HOXA cluster genes. Furthermore, the fusion transcript may be regarded as a potential minimal residual disease marker for SET-NUP214-positive patients. Episomal amplifications of NUP214-ABL1 are specific to T-ALL patients. The NUP214-ABL1 gene is observed in ~6% of T-ALL, in children and adults. Targeted tyrosine kinase inhibitors plus standard chemotherapy appear to present a promising treatment strategy. DEK-NUP214 is formed by the fusion of exon 2 of DEK and exon 6 of NUP214. Achieving molecular negativity of DEK-NUP214 is of great importance for individual management. SQSTM1 NUP214 and NUP214-XKR3 were only identified in one T-ALL patient and one cell line, respectively. The NUP214 fusions have significant diagnostic and therapeutic implications for leukemia patients. Additional NUP214-associated fusions require identification in future studies. PMID- 25120642 TI - Aberrant DNA methylation in hepatocellular carcinoma tumor suppression (Review). AB - Aberrant DNA methylation leads to altered gene expression, resulting in cancerous features. Numerous tumor suppressor genes are silenced by DNA methylation during hepatocarcinogenesis. Promoter CpG island hypermethylation is an important mechanism for inactivating tumor suppressor genes in hepatocellular carcinoma (HCC). Hypermethylation of CpG islands in the p16 (INK4a) and p15 (INK4b) promoters may increase the risk of developing HCC, particularly hepatitis B virus related HCC. Environmental factors can lead to geographic variations in the methylation status of CpG islands. Aberrant DNA methylation of CpG islands is catalyzed by DNA methyltransferases (DNMTs). Thus, abnormal variations of DNMTs can contribute to hepatocarcinogenesis. In hepatitis-related HCC, microRNAs participate in hepatocarcinogenesis by directly targeting DNMTs, during which hepatitis B virus X acts as a regulator. DNA methylation may also contribute to HCC tumorigenesis by regulating the cell cycle. Based on the importance of DNA methylation in tumor suppression of HCC, certain DNA methylations may predict the risk of tumor development, tumor staging, patient survival and HCC recurrence. PMID- 25120643 TI - Potential new role of the GHSR-1a-mediated signaling pathway in cardiac remodeling after myocardial infarction (Review). AB - The gastrointestinal hormone ghrelin has important cardiovascular protective effects, however, its specific mechanisms are not yet completely understood. Recent studies have shown that the ghrelin receptor, growth hormone secretagogue receptor type 1a (GHSR-1a), regulates cell proliferation, apoptosis and inflammation-related signaling pathways. In human aortic endothelial cells, ghrelin activates NO production through AMP-activated protein kinase (AMPK) and Akt activation, and these effects can be blocked by knockdown of GHSR-1a. Obese mice have been found to exhibit an increased GHSR-1a content and expression in the heart, associated with an increase in phosphatidylinositol 3-kinase (PI3K) content and an increase AKT content and phosphorylation. Furthermore, GHSR-1a expression was observed to be increased in heart failure after myocardial infarction (MI) in rats. Given such complexity in GHSR-1a signaling and crosstalk with the AMPK and PI3K/Akt signaling pathways, both of which are well-known factors involved in cardiac remodeling after MI, we speculate that GHSR-1a signaling may play a regulatory role in cardiac protection and hope to identify new drugs targets. However, to date, no direct association between GHSR-1a and cardiac remodeling has been found. Therefore, further studies are required. PMID- 25120644 TI - Normal tissue studies in radiation oncology: A systematic review of highly cited articles and citation patterns. AB - Radiation therapy is one of the cornerstones of modern multidisciplinary cancer treatment. Normal tissue tolerance is critical as radiation-induced side effects may compromise organ function and quality of life. The importance of normal tissue research is reflected by the large number of scientific articles, which have been published between 2006 and 2010. The present study identified important areas of research as well as seminal publications. The article citation rate is among the potential indicators of scientific impact. Highly cited articles, arbitrarily defined as those with >=15 citations, were identified via a systematic search of the citation database, Scopus. Up to 608 articles per year were published between 2006 and 2010, however, <10% of publications in each year accumulated >=15 citations. This figure is notably low, when compared with other oncology studies. A large variety of preclinical and clinical topics, including toxicity prediction, the dose-volume relationship and radioprotectors, accumulated >=15 citations. However, clinical prevention or mitigation studies were underrepresented. The following conclusion may be drawn from the present study; despite the improved technology that has resulted in superior dose distribution, clinical prevention or mitigation studies are critical and must receive higher priority, funding and attention. PMID- 25120645 TI - Colorectal laterally spreading tumors show characteristic expression of cell polarity factors, including atypical protein kinase C lambda/iota, E-cadherin, beta-catenin and basement membrane component. AB - Colorectal flat-type tumors include laterally spreading tumors (LSTs) and flat depressed-type tumors. The former of which shows a predominant lateral spreading growth rather than an invasive growth. The present study examined the morphological characteristics of LSTs, in comparison with polypoid- or flat depressed-type tumors, along with the expression of atypical protein kinase C (aPKC) lambda/iota, a pivotal cell polarity regulator, and the hallmarks of cell polarity, as well as with type IV collagen, beta-catenin and E-cadherin. In total, 37 flat-type (24 LSTs and 13 flat depressed-type tumors) and 20 polypoid type colorectal tumors were examined. The LSTs were classified as 15 LST adenoma (LST-A) and nine LST cancer in adenoma (LST-CA). An immunohistochemical examination was performed on aPKC lambda/iota, type IV collagen, beta-catenin and E-cadherin. The LST-A and -CA showed a superficial replacing growth pattern, with expression of beta-catenin and E-cadherin in the basolateral membrane and type IV collagen along the basement membrane. In addition, 86.6% of LST-A and 55.6% of LST-CA showed aPKC lambda/iota expression of 1+ (weak to normal intensity staining in the cytoplasm compared with the normal epithelium). Furthermore, ~45% of the polypoid-type adenomas showed 2+ (moderate intensity staining in the cytoplasm and/or nucleus) and 66.7% of the polypoid-type cancer in adenoma were 3+ (strong intensity staining in the cytoplasm and nucleus). A statistically significant positive correlation was observed between the expression of aPKC lambda/iota and beta-catenin (r=0.842; P<0.001), or type IV collagen (r=0.823; P<0.001). The LSTs showed a unique growth pattern, different from the expanding growth pattern presented by a polypoid tumor and invasive cancer. The growth characteristics of LST appear to be caused by adequate coexpression of beta catenin, type IV collagen and aPKC lambda/iota. PMID- 25120647 TI - Matrigel induces L-plastin expression and promotes L-plastin-dependent invasion in human cholangiocarcinoma cells. AB - The function of the extracellular matrix (ECM) in the tumor microenvironment is not limited to forming a barrier against tumor invasion. As demonstrated in pathological specimens, cholangiocarcinoma samples exhibit an enrichment of the ECM surrounding the tumor cells. In this study, we examined involvement of the ECM in the regulation of the invasiveness of cholangiocarcinoma cells. The RMCCA1 cholangiocarcinoma cell line was cultured in culture plates either with or without a coating of reconstituted ECM basement membrane preparation (BD Matrigel matrix). In vitro invasion assays were then performed. In addition, the protein expression profile of the cell line was examined using two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry. The proteins expressed and their functional associations with cancer progression were determined. Culturing the RMCCA1 cell line in the BD Matrigel matrix induced cell invasion. Numerous proteins were induced by culturing the RMCCA1 cells in the matrix gel. The expression of L-plastin, an actin-binding protein, was significantly upregulated. The knockdown of L-plastin expression by siRNA silencing significantly suppressed the cellular response to matrix gel-stimulated cancer cell invasion. The ECM promotes the invasiveness of cholangiocarcinoma cells by upregulating L-plastin. These findings suggest the potential exploitation of this mechanism as a means of inhibiting the invasiveness of cholangiocarcinoma cells. PMID- 25120646 TI - Immunohistochemical expression of four different stem cell markers in prostate cancer: High expression of NANOG in conjunction with hypoxia-inducible factor 1alpha expression is involved in prostate epithelial malignancy. AB - Cancer stem cells (CSCs) have been identified in a variety of cancer types, including prostate cancer. The aim of the present study was to evaluate the immunohistochemical expression of NANOG, octamer 4 (OCT4), cluster of differentiation 133 (CD133) and NESTIN, which are all CSC markers, and assess their function in prostate carcinogenesis. A total of 114 patients were referred to the Kanazawa Medical University Hospital (Uchinada, Japan) having presented with elevated serum prostate-specific antigen levels and/or abnormal digital rectal examinations, and underwent transrectal ultrasound sonography guided eight core biopsies. The prostate pathological specimens were re-evaluated for selection in this study. When specimens were diagnosed as prostate cancer, immunohistochemical analysis of the four different stem cell markers (NANOG, OCT4, CD133 and NESTIN) and hypoxia-inducible factor (HIF)-1alpha was performed. Prostate cancer was found in 38 cases (33.3%), while the other patients had benign prostate hyperplasia with prostatitis. All prostate cancers were histopathologically identified as adenocarcinomas of various grades, and cancer cells and intraepithelial neoplasia (high grade) were immunohistochemically shown to express NANOG and OCT4, but not CD133 and NESTIN. The intensity of NANOG expression was much greater than that of OCT4, and the positivity and intensity of the four stem cell markers, including NANOG, were elevated with high Gleason scores. A significant correlation was observed between the NANOG- and HIF-1alpha positive regions. The CSC markers, in particular OCT4 and NANOG, were immunohistochemically expressed in prostate cancers. Furthermore, HIF-1alpha expression may affect NANOG and/or OCT4 expression. The findings of the current study suggested that NANOG expression may be a biomarker for the diagnosis of prostate cancer, and the coexpression of NANOG and HIF-1alpha may be involved in prostate carcinogenesis. PMID- 25120648 TI - Coexistence of t(15;17) and t(15;16;17) detected by fluorescence in situ hybridization in a patient with acute promyelocytic leukemia: A case report and literature review. AB - Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid alpha-receptor (RARA) gene at 17q21. The current study presents the case of a 54-year-old female with APL carrying the atypical PML/RARA fusion signal due to a novel complex variant translocation t(15;16;17)(q22;q24;q21), as well as the classical PML/RARA fusion signal. Subsequent array comparative genomic hybridization revealed somatic, cryptic deletions on 3p25.3, 8q23.1 and 12p13.2-p13.1, and a duplication on 8q11.2; however, no genetic material loss or gain was observed in the breakpoint regions of chromosomes 15, 16 or 17. To the best of our knowledge, this is the first report of the coexistence of two abnormal clones, one classical and one variant, presenting simultaneously in addition to cryptic chromosome segmental imbalances in an adult APL patient. PMID- 25120649 TI - Telomerase Cajal body protein 1 depletion inhibits telomerase trafficking to telomeres and induces G1 cell cycle arrest in A549 cells. AB - Telomerase Cajal body protein 1 (TCAB1) is a telomerase holoenzyme, which is markedly enriched in Cajal bodies (CBs) and facilitates the recruitment of telomerase to CBs in the S phase of the cell cycle. This recruitment is dependent on TCAB1 binding to a telomerase RNA component. The majority of cancer cells are able to grow indefinitely due to telomerase and its mechanism of trafficking to telomeres. In the present study, a certain level of TCAB1 expression in A549 human lung cells was identified and TCAB1 knockdown exhibited a potent antiproliferative effect on these cells, which was coupled with a decrease in the cell density and activity of the cellular enzymes. In addition, TCAB1-depletion was demonstrated to inhibit telomerase trafficking to telomeres in the A549 cells, leading to subsequent G1 cell cycle arrest without inducing apoptotic cell death. Overall, these observations indicated that TCAB1 may be essential for A549 cell proliferation and cell cycle regulation, and may be a potential candidate for the development of a therapeutic target for lung adenocarcinomas. PMID- 25120650 TI - Clinical significance of the 'not otherwise specified' subtype in candidates for resectable non-small cell lung cancer. AB - The histological subtype of non-small-cell lung cancer (NSCLC) is a significant factor when selecting treatment strategies. However, cases are occasionally encountered that are diagnosed as 'not otherwise specified' (NOS) prior to surgery, due to an uncertain histological subtype. The present study investigated the prognostic significance of the NOS subtype for patients with resectable NSCLC. Between 2001 and 2011, 1,913 patients were diagnosed with NSCLC using transbronchial biopsy and underwent surgical resection at two facilities in Japan. Of these patients, 151 (7.9%) were pre-operatively diagnosed with NSCLC NOS (NOS group) and the remainder had confirmed histological subtypes (confirmed group). The present study compared the clinicopathological features and prognoses of these groups. Analyses of resected specimens revealed that pleomorphic cell carcinoma, large cell neuroendocrine cell carcinoma, large cell carcinoma and adenosquamous carcinoma were significantly more common in the NOS group than in the confirmed group (P<0.001, P=0.002, P=0.019 and P=0.014, respectively). The five-year survival rate was significantly poorer in the NOS group (60.5 vs. 67.1%; P=0.010), particularly for stage I disease (70.8 vs. 80.7%; P=0.007). The results of a multivariate analysis of overall survival indicated that NOS was a significant independent prognostic factor (hazard ratio, 1.40; 95% confidence interval, 1.02-1.86; P=0.041). These results indicated that pre-operative NOS was significantly associated with poorer survival, including for stage I disease. In conjunction with other clinicopathological parameters, NOS can be a useful prognostic factor when deciding on a treatment strategy for NSCLC. PMID- 25120651 TI - Aberrant methylation and silencing of IRF8 expression in non-small cell lung cancer. AB - The aim of the present study was to investigate the aberrant methylation and altered expression of the interferon regulatory factor 8 (IRF8) gene in non-small cell lung cancer (NSCLC). Pyrosequencing assays were performed on 191 tumor specimens from NSCLC patients. The changes in IRF8 mRNA expression, prior to and following treatment with a demethylating agent and methylation itself, were examined in 13 lung cancer cell lines by quantitative polymerase chain reaction (qPCR) and pyrosequencing. IRF8 protein expression was examined in 94 of the 191 NSCLC specimens by immunohistochemical analysis. The IRF8 methylation level was significantly higher in the tumor tissues than in matched non-malignant lung tissues (P<0.0001). IRF8 was more frequently methylated in tumor tissues compared with matched non-malignant lung tissues, as defined by a predetermined cut-off value (P<0.0001). The IRF8 methylation level was strongly correlated with the change in mRNA expression in lung cancer cell lines and with the protein expression level in primary tumors. The IRF8 gene was more frequently methylated in patients without an epidermal growth factor receptor (EGFR) mutation than in patients with an EGFR mutation (P=0.015). IRF8 methylation correlated with recurrent prognosis in adenocarcinomas (log-rank test, P=0.048). IRF8 protein expression was frequently silenced in males, smokers, patients with non adenocarcinoma or with wild-type EGFR, or in an advanced stage. IRF8 is often silenced by its methylation, which is a frequent event in NSCLC and, therefore, methylation of IRF8 may act as a prognostic marker for recurrence. Analysis of IRF8 methylation status may provide novel opportunities for improved prognosis and therapy of resected NSCLC. PMID- 25120652 TI - Long-term urodynamic evaluation of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer. AB - The long-term urodynamics of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer remain unclear in the clinical setting. The present prospective observational study was conducted between January 2010 and December 2012 to evaluate the 6-month and 12-month follow-up data of urodynamic changes of bladder cancer patients who were initially treated by laparoscopic radical cystectomy with orthotopic ileal neobladder. A total of 53 eligible patients were included, and all patients were followed up for at least 12 months, with a median time of 18 months. During the follow-up period, no patients reported difficulty urinating, and the daily frequency of urination and the urine output were gradually improved with time. Dynamic urodynamic examinations showed that the maximum flow rate (11.4+/-1.1 vs. 7.3+/-1.4 ml/sec; P<0.001), residual urine content (22.8+/-10.5 vs. 40.7+/-12.7 ml; P<0.001), maximum bladder capacity (373.8+/-62.2 vs. 229.7+/-56.3 ml; P<0.001) and maximum bladder pressure during filling (35.8+/-6.7 vs. 26.4+/-7.0 cm H2O; P<0.001) at 12 months were all improved significantly compared with that at 6 months after the initial surgical treatment. However, there were no significant differences in maximum bladder pressure during voiding (75.7+/-24.7 vs. 73.1+/-24.7 cm H2O; P=0.618) and bladder compliance (26.9+/-13 vs. 27.4+/-13.1 cm H2O; P=0.848) at 12 and 6 months after initial surgical treatment. In conclusion, the urodynamics of this orthotopic ileal neobladder gradually improve, and its long-term urine storage and voiding functions are acceptable. PMID- 25120653 TI - Tonsil neuroendocrine carcinoma concurrent with hepatocellular carcinoma: A case report. AB - The majority of neuroendocrine tumors appear to be sporadic. Neuroendocrine carcinoma (NEC) typically arises in pancreatic, parathyroid and adrenal glands, but rarely arises in salivary glands. NEC of the tonsil is a rare type of tumor and the concurrent presentation of hepatocellular carcinoma (HCC) is considered to be more uncommon. There are few case reports of NEC of the tonsil in the literature and to date no studies have been conducted to establish its optimal management. The current study presents a case of a 72-year-old male who presented with left neck and tonsil tumors. A biopsy from the tonsil revealed a NEC, and computed tomography showed liver cirrhosis, multiple liver cancers and portal vein thrombosis, as well as metastasis to the hilar, abdomen and retroperitoneum. Histological examination of the hepatic revealed primary HCC. To the best of our knowledge, this is a condition that has not previously been reported. PMID- 25120654 TI - Lung adenocarcinoma harboring L858R and T790M mutations in epidermal growth factor receptor, with poor response to gefitinib: A case report. AB - Lung cancer is the leading cause of mortality among malignant diseases in humans worldwide. During the last decade, molecular targeted therapies for non-small cell lung cancer using first-generation, reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib, have been shown to be a promising approach for patients harboring activating mutations in EGFR. The current study reports a 77-year-old patient diagnosed with adenocarcinoma harboring L858R and T790M point mutations in the EGFR gene. The patient was treated with gefitinib as the second-line therapy, but no clinical benefit was observed. As the majority of patients with lung cancer receiving EGFR TKI therapy acquire resistance, repeated biopsies and detection of the EGFR mutation state are beneficial for selecting appropriate treatments. PMID- 25120656 TI - Human cytomegalovirus inhibits apoptosis by regulating the activating transcription factor 5 signaling pathway in human malignant glioma cells. AB - The activating transcription factor 5 (ATF5), also termed ATFx, is a member of the ATF/cAMP response element-binding protein (CREB) family of basic zipper proteins. ATF5 is an anti-apoptotic protein that is highly expressed in malignant glioma and is essential for glioma cell survival. Accumulating evidence indicates that human malignant gliomas are universally infected with human cytomegalovirus (HCMV). Recent studies have shown that HCMV may be resistant to the induction of apoptosis by disrupting cellular pathways in glioblastoma. To investigate the potential anti-apoptotic function of HCMV in glioma, malignant U87 glioma cells were infected with HCMV. The present study showed that HCMV infection suppressed apoptosis in glioblastoma U87 cells by regulating the expression of ATF5. Furthermore, in glioblastoma U87 cells, HCMV infection induced cellular proliferation in parallel with an increase in the expression level of ATF5 and B cell lymphoma/leukemia-2 to Bcl-2-associated X protein ratio. Loss of ATF5 function was achieved using a dominant-negative form of ATF5 in U87 cells, whereby cells appeared to grow marginally following HCMV infection when compared with the control. However, the anti-apoptotic ability was appeared to decline in the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. These results indicate that ATF5 signaling pathways may be important in the anti apoptotic activity of HCMV-infected glioblastoma cells; therefore, the anti apoptotic molecular mechanisms of HCMV in human glioblastoma cells were investigated in the current study. Prevention of HCMV infection may present a potential and promising approach for the treatment of malignant gliomas. PMID- 25120657 TI - Phosphatase and tensin homolog overexpression decreases proliferation and invasion and increases apoptosis in oral squamous cell carcinoma cells. AB - Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor which regulates various cellular functions. The aim of the present study was to analyze the function of PTEN gene expression in squamous cell carcinoma (SCC) cells. This gene exhibits a unique function in cell migration and proliferation during the early stages of embryonic development. However, its role as a tumor suppressor gene in tongue squamous carcinoma cells remains unclear. In the present study, an SCC-4 cell line stably expressing PTEN was established and the effects of PTEN gene expression on SCC-4 cell proliferation, invasion and apoptosis were investigated. PTEN expression was found to induce apoptosis in SCC-4 cells, possibly via negative regulation of the phosphatidylinositide 3-kinase/Akt signaling pathway and increased expression of Bcl-2-interacting mediator of cell death. In addition, PTEN was found to control the epithelial-mesenchymal transition in SCC cells, thereby reducing their invasive ability. Furthermore, Transwell assay revealed that the expression of E-cadherin was increased, while the expression of vimentin and SNAIL was decreased. This study has provided an important insight into the mechanisms by which PTEN mediates the progression and early metastasis of tongue carcinoma. PMID- 25120655 TI - miR-320a is an independent prognostic biomarker for invasive breast cancer. AB - Breast cancer is one of the most common malignancies worldwide and is the second leading cause of cancer-related mortality among females. miRNAs are a class of small noncoding RNAs that are aberrantly expressed in human cancers. Due to their small size and stability, miRNAs have the potential to be efficacious clinical targets. MicroRNA-320a (miR-320a) has been shown to be dysregulated in multiple malignancies. In the present study, the expression levels of miR-320a were investigated in 15 paraffin-embedded in situ breast carcinoma and 130 invasive breast cancer tissues, and the prognostic value for breast cancer patients was assessed. Chromogenic in situ hybridization revealed that 60/130 (46%) invasive breast cancer tissues exhibited high expression levels of miR-320a (staining index score of >=4). Furthermore, miR-320a staining was found to significantly correlate with tumor size (P=0.046), clinical stage (P<0.001), lymph node metastasis (P<0.001) and distant metastasis (P=0.006). In addition, patients exhibiting low miR-320a expression levels had shorter overall survival times (P<0.001). Univariate and multivariate analyses revealed that miR-320a was an independent prognostic biomarker for invasive breast cancer (hazard ratio, 0.221; 95% confidence interval, 0.050-0.979; P=0.047). Receiver operator characteristic curves revealed that the prognostic value of miR-320a was enhanced when compared with the widely used prognostic biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor-2) in invasive breast cancer. The results of the present study suggest that miR-320a presents a potential biomarker for the prognosis of invasive breast cancer, and dysregulation of miR-320a may be involved in invasive breast cancer progression. PMID- 25120658 TI - Submucosal small-cell neuroendocrine carcinoma of the larynx detected using 18F fluorodeoxyglucose positron emission tomography/computed tomography: A case report and review of the literature. AB - A 67-year-old male presented with a metastatic carcinoma in the right side of the neck from an unknown primary site. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed increased 18F-FDG uptake in the right larynx and right neck lymph nodes. A smooth lesion was identified in the submucosa of the right supraglottic region via a suspension laryngoscopy under general anaesthesia. A biopsy was performed and a frozen section revealed a small cell (SC) carcinoma. A total laryngectomy and bilateral neck dissection were performed simultaneously, and the pathological results demonstrated a SC neuroendocrine carcinoma. The patient received chemo-radiotherapy postoperatively, however, succumbed due to distant metastasis one year following surgery. PMID- 25120659 TI - Misdiagnosis of pancreatic papillary mucinous cystadenocarcinoma: A case report. AB - The morbidity of papillary cystadenocarcinoma of the pancreas is extremely low and the condition is rarely first found as spinal metastases, thus it is often misdiagnosed prior to surgery. The present study reports a case of papillary cystadenocarcinoma with thoracolumbar metastases in a 56-year-old male. The first symptom to occur was backache, however, computed tomography revealed no positive findings. The pain became exacerbated and the patient underwent lumbar and thoracic vertebrae magnetic resonance imaging, which identified abnormal signals. Imaging and pathological examinations were used for the final diagnosis. Due to multiple bone metastases, the patient the administration of induction chemotherapy was suggested, however, the patient refused. The patient succumbed to the disease in June 2013. PMID- 25120660 TI - Multifocal Langerhans cell histiocytosis in an adult with a pathological fracture of the mandible and spontaneous malunion: A case report. AB - Langerhans cell histiocytosis (LCH) is rare in the adult population and even rarer with jaw involvement. The current study presents the case of a 39-year-old male who complained of recurrent pain, swelling of the gingiva and an occasional pus-like discharge in the right mandible for one year. The patient was previously prescribed antibiotics, but this did not resolve the problem. An initial panoramic radiograph showed an osteolytic lesion and bone fracture in the right mandible. Eight months later, a new radiograph showed the spontaneous malunion of the fractured mandible. The patient was eventually diagnosed with Langerhans cell histiocytosis by histopathology and immunohistochemistry. Further lesions were found in the ribs and ilium by nuclear bone scanning. The patient was subsequently treated with systemic chemotherapy, and the lesions are currently effectively being controlled. This study is the first to show that spontaneous intralesional bone regeneration may lead to reunification of the mandible fracture caused by LCH in an adult. PMID- 25120662 TI - Shikonin promotes autophagy in BXPC-3 human pancreatic cancer cells through the PI3K/Akt signaling pathway. AB - The present study aimed to investigate the effect of shikonin on autophagy in BXPC-3 human pancreatic cancer cells and its underlying mechanism. Cell viability was assessed using the Cell Counting Kit-8 assay and the expression of light chain (LC) 3, p62, phosphoinositide 3-kinase (PI3K), Akt, phosphorylated (p)-PI3K and p-Akt was analyzed using western blot analysis. Following treatment with 1 MUmol/l shikonin for 48 h and 2.5 and 5 MUmol/l shikonin for 24 and 48 h, the viability of the BXPC-3 cells was found to be significantly reduced and the protein expression of LC3-II/LC3-I was observed to be increased, while the protein expression of p62, PI3K, Akt, p-PI3K and p-Akt was decreased. These findings suggest that shikonin promotes autophagy in BXPC-3 cells and that the underlying mechanism may be associated with the PI3K/Akt signaling pathway. PMID- 25120661 TI - Clinical significance of aberrant mammalian target of rapamycin expression in stage IIIB colon cancer. AB - The aim of the present study was to investigate the significance of aberrant expression of mammalian target of rapamycin (mTOR) and the activated form of mTOR kinase, phosphorylated mTOR (pmTOR), in human stage IIIB colon cancer. The expression of mTOR and pmTOR was detected by immunohistochemistry in the tumor tissue of stage IIIB colon cancer patients. The association between the expression of mTOR, pmTOR and clinicopathological parameters of patients was analyzed. The positive expression of mTOR and pmTOR was observed to be higher in 75.5% (80/106) and 76.4% (81/106) of the 106 colon cancer specimens, compared with the adjacent normal tissues. The high level of pmTOR expression was found to be significantly higher in the invasive tumor front cells and resulted in a higher risk of mortality. The results suggested that mTOR and pmTOR may be promising clinical markers and present novel molecular targets for designing novel therapeutic strategies to treat this malignancy. PMID- 25120663 TI - A 4-cm lipoma of the transverse colon causing colonic intussusception: A case report and literature review. AB - Colonic lipomas are rare benign tumors. Colonic intussusception is an uncommon complication of colonic lipoma. The current study presents an unusual case of a 4 cm symptomatic lipoma of the transverse colon causing colonic intussusception. A 65-year-old female was admitted to Wenzhou Central Hospital (Wenzhou, Zhejiang, China) with intermittent pain in the left abdomen that had been present for two weeks. Colonoscopy revealed a 4*5-cm intraluminal spherical mass with erosional mucosa 60 cm above the anal verge, indicating the presence of a malignant gastrointestinal stromal tumor. Contrast-enhanced computed tomography revealed a well-defined fatty tissue mass of 4 cm in diameter in the distal transverse colon proximal to the splenic flexure, with intussusception. The patient underwent segmental resection of the transverse colon and intraoperative frozen sections were obtained. The intraoperative frozen sections revealed a submucosal lipoma of the transverse colon and thus, a conclusive diagnosis was achieved. The patient was followed up for one year and 10 months following the segmental resection of the transverse colon, with a good prognosis. This study may increase clinical awareness with regard to colonic lipomas. Furthermore, open surgery combined with use of intraoperative frozen sections should be recommended for large symptomatic colonic lipomas accompanied by colonic intussusception, thus avoiding unnecessary radical resection and improving patient prognosis. PMID- 25120664 TI - Polymorphism of the p38beta gene in patients with colorectal cancer. AB - The p38 mitogen-activated protein kinase (MAPK) signaling pathways have been proposed to participate in the pathological process of cancer by affecting inflammation, proliferation, metastasis and cell survival. A single nucleotide polymorphism (SNP; rs2235356, -1628A->G) in the promoter region of the p38beta gene has been proposed as a genetic modifier for colorectal cancer (CRC) in a Chinese population. The present study evaluated the susceptibility of patients possessing this SNP to CRC, in addition to determining its association with clinical parameters in Swedish patients with CRC. Using the LightSNiP genotyping assay, this SNP was screened in 389 patients with CRC and 517 control subjects. No significant difference in the genotype distribution or in the allelic frequencies was identified between the two groups nor was any association identified with the clinical parameters. These findings indicate that the -1628A >G polymorphism of the p38beta gene is not significantly associated with a susceptibility to CRC in a Swedish population. PMID- 25120665 TI - Combination of autoantibodies against NY-ESO-1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and Southeast Asia, and early detection remains a challenge. Autoantibodies have been found to precede the manifestations of symptomatic cancer by several months to years, making their identification of particular relevance for early detection. In the present study, the diagnostic value of serum autoantibodies against NY-ESO-1 in NPC patients was evaluated. The study included 112 patients with NPC and 138 normal controls. Serum levels of autoantibodies against NY-ESO-1 and classical Epstein-Barr virus marker, viral capsid antigen immunoglobulin A (VCA-IgA), were measured by enzyme-linked immunosorbent assay. Measurement of autoantibodies against NY-ESO-1 and VCA-IgA demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval (CI), 33.7-52.6/89.4-97.8%] and 55.4/95.7% (95% CI, 45.7-64.7/90.4-98.2%), respectively. The area under receiver operating characteristic curve for autoantibodies against NY-ESO-1 (0.821; 95% CI, 0.771-0.871) was marginally lower than that for VCA-IgA (0.860; 95% CI, 0.810-0.910) in NPC. The combination of autoantibodies against NY-ESO-1 and VCA-IgA yielded an enhanced sensitivity of 80.4% (95% CI, 71.6-87.0%) and a specificity of 90.6% (95% CI, 84.1-94.7%). Moreover, detection of autoantibodies against NY-ESO-1 could differentiate early stage NPC patients from normal controls. Our results suggest that autoantibodies against NY-ESO-1 may serve as a potential biomarker, as a supplement to VCA-IgA, for the screening and diagnosis of NPC. PMID- 25120666 TI - Extended curettage and heat ablation for desmoplastic fibroma of the distal femur with a 12-year follow-up period: A case report. AB - Desmoplastic fibroma is a particularly rare, benign but locally aggressive, primary bone tumor. Owing to previously published reports stating high recurrence rates following curettage, the recommended primary treatment for desmoplastic fibroma is a marginal to wide tumor resection. In the current report, the case of an athlete with desmoplastic fibroma of the distal femur who was treated with extended curettage, heat ablation and artificial bone grafting is described. The postoperative course was uneventful and no recurrence has been observed during the 12-year follow-up period. The patient is able to sit on his heels with a straight back, without pain and is able run a complete marathon. PMID- 25120667 TI - Lymphatic invasion of micropapillary cancer cells is associated with a poor prognosis of pathological stage IA lung adenocarcinomas. AB - The cancer cells of lung adenocarcinoma with a micropapillary pattern (MPP) have been found to frequently invade lymphatic vessels, and the prognosis of patients with lung adenocarcinoma with an MPP is poor. In the present study, the cancer cells of lung adenocarcinomas containing an MPP were found to express vimentin more extensively than those in lung adenocarcinoma without an MPP. The contribution of cancer cells in the MPP component to adenocarcinoma lymphatic invasion was assessed using vimentin as a marker. Vimentin expression was analyzed in the cancer cells present in each lymphatic vessel and compared with the expression of vimentin in the cancer cells in the adenocarcinomas without an MPP component. The results showed that the cancer cells in the lymphatic vessels expressed vimentin more extensively than those in the adenocarcinoma components without an MPP, suggesting that cancer cells derived from an MPP component are present in the lymphatic vessels. By contrast, the area of the MPP component in each adenocarcinoma was <25%. These findings suggest that cancer cells in MPP components have a high capacity to invade lymphatic vessels and that their high invasive capacity may be associated with a poor prognosis in patients with adenocarcinoma with an MPP component. PMID- 25120668 TI - Interleukin 4, interleukin 6 and osteopontin-serological markers of head and neck malignancy in primary diagnostics: A pilot study. AB - The progression of head and neck squamous cell carcinoma (HNSCC) is stimulated by various angiogenic peptides and growth factors. A correlation between tumor progression and the secretion of various serological mediators in patients with malignant tumors of the head and neck is of major interest for tumor diagnostics, evaluation of the therapy response and it may predict prognosis by specifying the individual tumor biology. Established chemotherapeutic regimes for head and neck tumors usually consist of platinum-based chemotherapeutic drugs and 5 fluorouracil (5-FU). The present pilot study sought to assess the eligibility of seven serological factors as biomarkers for malignant tumors of the head and neck: Platelet-derived growth factor, vascular endothelial growth factor, epidermal growth factor receptor, osteopontin, granulocyte-colony stimulating factor, interleukin-4 (IL-4) and IL-6. The serum levels of each factor in 20 patients receiving concomitant radiochemotherapy with cisplatin or carboplatin and 5-FU with curative intent were determined prior and subsequent to chemotherapy and were compared with 40 healthy controls. Another aim of the pilot study was to investigate whether the serum of patients showed significant differences in the concentrations of the analyzed factors at the start of concomitant radiochemotherapy compared with the controls, whether those markers indicated a neoplastic process and whether concomitant radiochemotherapy with cisplatin or carboplatin and 5-FU induced significant alterations of concentration compared with pre-therapeutic levels. The included patients were histopathologically diagnosed with HNSCC and the average age was 62.3 years. The serum samples of the patients were obtained during the course of regular pre- and post-chemotherapeutic blood draws one week prior to the start of radiochemotherapy and one week following the completion of chemotherapy. The healthy controls were collected from patients of the Sleep Laboratory of the Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital (Mannheim, Germany) without clinical evidence or laboratory signs of inflammation or history of a malignant disease. The average age was 50.3 years. The serological level of each factor was ascertained by enzyme-linked immunosorbent assay in duplicate. Serum levels of IL-4, IL-6 and osteopontin were significantly increased in patients with HNSCC compared with those in chemotherapy-naive healthy controls. IL-4 and osteopontin showed no significant therapy-associated alterations. Notably, IL-6 levels significantly increased post-therapeutically. Using logistic regression with osteopontin and IL-4, an individual risk-profile for random samples was calculated. IL-4, IL-6 and osteopontin appear to be suitable indicators of the neoplastic process as they are significantly increased in HNSCC patients compared with the control group. With the exception of IL-6, whose levels were in fact increased following therapy, a significant therapy associated alteration of these factors was missing. Therefore, these serological markers failed to predict the therapy response, but they may be valuable as a screening instrument in primary diagnostics. PMID- 25120670 TI - Metachronous multiple gastrointestinal stromal tumors and adenocarcinoma of the colon: A case report. AB - Synchronous or metachronous occurrence of gastrointestinal stromal tumors (GISTs) and other primary gastrointestinal neoplasms has previously been reported. However, to the best of our knowledge, there are few studies regarding metachronous multiple GISTs and adenocarcinoma of the colon. The current case of an 80-year-old male patient who underwent a laparoscopic right hemicolectomy for colonic adenocarcinoma, located in the ascending colon, is presented. Twenty-one months after receiving the laparoscopic right hemicolectomy, two new disc-like bulge lesions in the descending colon and rectosigmoid were identified during an endoscopic follow-up examination, and a segmental bowel resection was performed. The final diagnosis of multiple colonic GISTs was established as a result of histopathological examination and immunohistochemistry. PMID- 25120669 TI - Polypoid colonic metastases from gastric stump carcinoma: A case report. AB - The present study aimed to investigate polypoid colonic metastases from gastric stump carcinoma by performing a retrospective analysis of the clinical data of a patient with such a diagnosis, and by discussing other previous case studies from the literature. The patient of the present study was an 80-year-old male who had undergone a gastrectomy 48 years previously for a benign perforated gastric ulcer. A colonoscopy revealed >10 multiple polypoid lesions of 6-10 mm in diameter distributed throughout the entire colon, except in the rectum. Each lesion had either erosion or a depression at the top and several were covered with a white fur-like substance. Biopsy specimens excised from the stomach showed a poorly-differentiated adenocarcinoma with diffuse signet ring cells, and a colonoscopy-guided biopsy revealed a signet ring cell adenocarcinoma. The patient was referred to the Oncology unit (Beijing Shijitan Hospital, Beijing, China) for assessment and chemotherapy treatment, which was initiated with 1,000 mg Xeloda orally administered twice a day for two-week courses every three weeks. The patient succumbed to upper gastrointestinal hemorrhage and pneumonia after three months. Gastric or gastric stump carcinoma may metastasize to the colon presenting as solitary or multiple colonic polyps. Thus, it is important to consider this diagnosis as such colon metastases may mimic solitary or multiple colonic polyps, which are commonly observed. A differential diagnosis is required in this complicated situation. PMID- 25120672 TI - Inflammatory cytokines induce vascular endothelial growth factor-C expression in melanoma-associated macrophages and stimulate melanoma lymph node metastasis. AB - Lymph node colonization by tumor cells is one of the key determinants of melanoma staging and prognosis, and tumor-associated macrophages (TAMs) are the predominant type of inflammatory cell in the tumor environment which secretes vascular endothelial growth factor (VEGF)-C, the most potent lymphangiogenic growth factor. In the present study, to elucidate the mechanism involved in VEGF C expression in TAMs, murine peritoneal macrophages were co-cultivated with syngeneic B16 melanoma cells to mimic the reciprocal interactions between tumor cells and macrophages found in spontaneous tumors. In the present study, upon contact with tumor cells, macrophages were found to express a higher level of VEGF-C which was associated with an increase in the expression of IL-1beta and TNF-alpha and their receptors. Antibodies against the IL-1beta and TNF-alpha receptors were added to media that had been conditioned by the macrophage-tumor cell co-cultures and inhibition of VEGF-C was observed in macrophages co cultivated with the tumor cells. Furthermore, when IL-1beta and TNF-alpha were used at a non-toxic level, they enhanced peritoneal lymph node colonization by melanoma cells. Thus, in the present study, macrophagic IL-1beta and TNF-alpha were observed to promote VEGF-C expression in TAMs, as well as melanoma lymph node metastasis, suggesting that inhibiting the signaling between tumor cells and TAMs may be required to inhibit lymphangiogenesis and lymph node metastasis. PMID- 25120671 TI - Undifferentiated embryonal liver sarcoma in childhood: A case report. AB - In order to improve the diagnosis and therapy of undifferentiated embryonal liver sarcoma (UELS), the present study presents the case of a 9-year-old female with UELS and discusses UELS in childhood. The patient presented with abdominal pain and fever. The laboratory tests, radiographic examination and pathological features presented by the female were similar to those of typical cases of UELS reported in childhood. The patient initially received surgical treatment and the immunohistochemical findings suggested that the patient had UELS. The patient's parents refused adjuvant chemotherapy and demonstrated a right prerenal mass 6 months post-surgery. Microscopic examination revealed that the tumor was evidence of undifferentiated embryonal sarcoma recurrence. However, the patient was comfortable and physical examination revealed no abnormal conditions. In addition, the laboratory results were normal. Abdominal computed tomography scan and ultrasound were performed every 3 months to monitor the tumor recurrence. At the time of writing, it has been 6 months after the second surgical procedure and there has been no appearence of abnormalities. Previous studies have shown that patients who receive combined therapy with complete tumor resection and adjuvant chemotherapy have a longer survival time than those who undergo surgical therapy alone. Complete tumor resection combined with adjuvant chemotherapy may reduce the risk of recurrence and enhance the survival time in patients with UELS. PMID- 25120674 TI - Chemotherapy-induced fulminant acute pancreatitis in pancreatic carcinoma: A case report. AB - Cases of chemotherapy-induced pancreatitis are rarely reported and among those diagnosed, the majority are mild and self-limiting. However, no previous cases of fulminant acute pancreatitis (FAP) induced by chemotherapeutic agents have been reported. The current study presents a case of FAP in a 62-year-old female on gemcitabine and capecitabine therapy. The patient was admitted to the China-Japan Friendship Hospital (Beijing, China) with the symptoms of acute pancreatitis two days after the completion of the first cycle of chemotherapy. Shock, hypoxemia and acute renal failure supervened, which resulted in mortality. As the common etiologies of pancreatitis were eliminated, a correlation between the incidence of FAP, and pancreatic cancer or chemotherapy, or both was suspected. Clinicians should be aware of this potential adverse effect when prescribing chemotherapeutic agents, particularly in patients with pre-existing risk factors for pancreatitis. PMID- 25120673 TI - Effect of daphnoretin on the proliferation and apoptosis of A549 lung cancer cells in vitro. AB - Daphnoretin is an active constituent of Wikstroemia indica C.A. Mey., which is widely distributed in the northwest and southwest regions of China. Previous studies have shown that daphnoretin has anticancer effects on leukemia, osteosarcoma and uterine cervix cancer cells. However, the effect of daphnoretin on human lung cancer cells has yet to be elucidated. In the present study, daphnoretin was observed to inhibit A549 lung cancer cell proliferation in a concentration- and time-dependent manner. Fluorescent microscopy and flow cytometric analysis showed that daphnoretin induced A549 cell apoptosis in a concentration-dependent manner. Western blot analysis also revealed that daphnoretin induced apoptosis through the regulation of the B-cell lymphoma-2 gene family in A549 cells. These findings indicate that daphnoretin may have potential as a therapeutic agent for the management of lung cancer. PMID- 25120675 TI - Primary adrenal nodular lymphocyte-predominant Hodgkin lymphoma: A case report and review of the literature. AB - Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma (HL), and is a rare disease manifestation in the adrenal gland, which is difficult to be diagnosed and treated. In the present study, we report a case of primary adrenal NLPHL in a 36-year-old male patient. The patient was without specific clinical signs and the definitive diagnosis was achieved by histological study. The patient underwent a laparoscopic left adrenalectomy and chemotherapy regimen of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). There is no standard treatment for adrenal NLPHL and therefore, treatment is based on that for other types of NLPHL, which includes radiotherapy and ABVD chemotherapy. Given the rarity of this disease, there are limited experiences with regard to its diagnosis and treatment. This study is useful for the differential diagnosis and treatment of adrenal masses. PMID- 25120676 TI - Primary chondrosarcoma presenting as an intrathoracic mass: A report of three cases. AB - Primary intrathoracic chondrosarcomas are rare tumors. The present study reports three cases of primary intrathoracic chondrosarcomas in two males and one female aged between 45 and 64 years. Clinically, one case presented with cough and blood sputum, while the other two cases of primary intrathoracic chondrosarcoma were found incidently during a routine health examination. Radiologically, the chondrosarcomas presented as large masses with intratumoral calcification. Chondrosarcoma should be distinguished from other calcified pulmonary lesions. In this study, all three cases underwent surgical treatment, and in one case, the surgery was accompanied by radiotherapy. To date, all patients have been followed up for between two and three years and are alive. PMID- 25120677 TI - Epithelioid angiosarcoma of the kidney: A case report and literature review. AB - Epithelioid angiosarcoma (EAS) is a rare disease which presents a great diagnostic challenge. The present study reports a case of EAS in the kidney in a 75-year-old male who presented with gross hematuria. An abdominal computed tomography scan revealed space-occupying lesions of the right kidney and renal cell carcinoma was suspected. Histological examination of the resected specimens showed pleomorphic epithelioid cells with vesicular nuclei, prominent nucleoli and eosinophilic cytoplasm that lined irregular vascular spaces. Immunohistochemical staining revealed that the tumor cells were positive for AE1/AE3, cytokeratin (CK) 7, vimentin, cluster of differentiation (CD) 31 and E cadherin, but showed no staining for CD10, CD34, factor VIII, CK20, carcinoembryonic antigen or desmin. Based on the histopathological and immunohistochemical findings, the patient was diagnosed with epithelioid angiosarcoma. Postoperative radiation therapy was administered and no recurrence was observed six months after surgery. PMID- 25120678 TI - Imaging observations of a schwannoma of low malignant potential in the anterior abdominal wall: A case report. AB - Neurilemmoma, also known as schwannoma, is an uncommon benign neoplasm that is most commonly found in the trunk and head and neck regions. The present study reports the case of a 67-year-old female with schwannoma localized in the anterior abdominal wall and analyzes the ultrasound and computed tomography (CT) imaging observations of the schwannoma. A dynamic time-intensity curve was also recorded in the study. A well-defined, elliptic low echo level, heterogeneous mass was observed during ultrasound examination. The CT scan revealed a solid, heterogeneous, low-density mass in the abdominal wall. Contrast-enhanced scans showed a heterogeneously enhanced mass during the arterial and venous phase. Centripetal fill-in was demonstrated and the mass was markedly, homogenously enhanced relative to the muscles during the delayed phase. Peak enhancement was observed during the venous phase and then slowly declined. However, the mass was hyperattenuated during the delayed phase. The lesion was completely excised and no evidence of recurrence has been identified during the 3 months of follow-up. The present study suggested that a diagnosis of schwannoma should be considered for certain patients with masses in the abdominal wall. Peripheral enhancement during the arterial and venous phases and homogeneous enhancement in the delayed phase are the significant imaging findings of a schwannoma. PMID- 25120679 TI - Never in mitosis gene A-related kinase 6 promotes cell proliferation of hepatocellular carcinoma via cyclin B modulation. AB - Never in mitosis gene A-related kinase (Nek) 6 is a recently identified Nek that is required for mitotic cell cycle progression; however, the role and mechanism of Nek6 activity during hepatocarcinogenesis is not well known. The aim of this study was to investigate the potential roles and internal mechanism of Nek6 in hepatocellular carcinoma (HCC) development. In the present study, Nek6 was found to be overexpressed in HCC samples and cell lines by florescent real-time quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. Furthermore, it was evidenced to contribute to oncogenesis and progression. The ectopic overexpression of Nek6 promoted cell proliferation and colony formation, whereas gene silencing of Nek6 inhibited these phenotypes, as documented in Huh7, PLC/PRF/5, Hep3B and HepG2 HCC cell lines. Mechanistic analyses indicated that Nek6 regulates the transcription of cyclin B through cdc2 activation, and promotes the accumulation of G0/G1-phase cells. In conclusion, the findings of the current study suggested that Nek6 contributes to the oncogenic potential of HCC, and may present as a potential therapeutic target in this disease. PMID- 25120680 TI - Expression of WASF3 in patients with non-small cell lung cancer: Correlation with clinicopathological features and prognosis. AB - Wiskott-Aldrich syndrome protein family member 3 (WASF3) is required for invasion and metastasis in different cancer cell types, and has been demonstrated to possess prognostic value in various types of human cancer. However, to the best of our knowledge, the expression profile of WASF3 and its correlations with the clinicopathological features of non-small cell lung cancer (NSCLC) have not yet been described. In the present study, the mRNA expression levels of WASF3, in 38 NSCLC patients and in matched normal tissues, were assessed using quantitative polymerase chain reaction and the protein expression in 96 specimens was analyzed using immunohistochemistry. In addition, patient survival data were collected retrospectively and the association between WASF3 expression and five-year overall survival was evaluated. The results demonstrated that the mRNA expression level of WASF3 in cancer tissues was markedly (approximately five times) higher compared with that of the normal tissues. The WASF3 protein expression profile in NSCLC was consistent with the mRNA expression result, which also correlated with the histological subtype and tumor stage. Furthermore, patients with WASF3 positive expression were associated with a poorer prognosis compared with those exhibiting WASF3-negative expression, and the five-year survival rate was 20.8 and 46.5%, respectively (Kaplan-Meier; log-rank, P=0.004). In the multivariate analysis, which included other clinicopathological features, WASF3 emerged as an independent prognostic factor (relative risk, 0.463; 95% CI, 0.271-0.792). These results indicate that WASF3 may be critical in the pathogenesis of NSCLC, in addition to being a valuable prognostic factor for NSCLC patients. Further investigations are required to identify the efficacy of WASF3 as a potential therapeutic target for the treatment of NSCLC. PMID- 25120681 TI - Nicotinamide N-methyltransferase is overexpressed in prostate cancer and correlates with prolonged progression-free and overall survival times. AB - Nicotinamide N -methyltransferase (NNMT) has been identified to be associated with tumorigenesis and the malignant transformation of numerous types of cancer. The aim of the present study was to explore the expression and prognostic significance of NNMT in prostate cancer (PCa). Immunohistochemical NNMT expression was examined in 26 cases of benign prostate hyperplasia (BPH), 18 cases of high-grade prostatic intraepithelial neoplasia (HGPIN) and 120 cases of PCa. While rarely expressed in BPH (8/26 cases; 30.8%), NNMT was found to be significantly upregulated in HGPIN (15/18 cases; 83.3%) and PCa (77/120 cases; 64.2%). Clinicopathological analysis revealed that NNMT expression was negatively correlated with Gleason score (P<0.001). Furthermore, Kaplan-Meier survival curves revealed that high NNMT expression was associated with prolonged progression-free survival (PFS) and overall survival (OS) times in patients with advanced PCa. Multivariate analysis showed that NNMT was an independent prognostic marker of PFS and OS in patients with advanced PCa. The results of the present study suggested that NNMT may contribute to the development of PCa and may potentially be a favorable prognostic marker for the survival of patients with advanced PCa. PMID- 25120682 TI - Periductal stromal sarcoma of the breast: A case report and review of the literature. AB - Periductal stromal sarcoma (PSS), spindle and epithelioid types, is a rare subtype of malignant fibroepithelial tumor. The morphological characteristics of this neoplasm are different from phyllodes tumor and stromal sarcoma. PSS exhibits biphasic histology with benign ductal elements and a sarcomatous stroma composed of spindle cells and lacking phyllodes tumor architecture. The therapeutic management of PSS is based on wide surgery with free margins, and adjuvant therapies are not required. To the best of our knowledge, the recurrence of PSS in <=5 months has not been reported in the literature to date. This report describes a 43-year-old woman who presented to our hospital with a recurrence of nodules in the left breast. The patient had undergone lumpectomy at a different hospital 5 months previously, and a diagnosis of phyllodes tumor was pathologically confirmed. On presentation at our hospital, the patient underwent a second lumpectomy. Histological examination revealed PSS and the patient underwent a simple mastectomy of the left breast with no adjuvant treatment (such as chemotherapy or radiotherapy). After 9 months of close follow-up examinations, no recurrence was observed. PSS is an extremely rare disease with low-grade sarcomatous behavior, which may evolve into a phyllodes tumor or an entity of breast cancer. Therefore, frequent follow-up examinations are required. PMID- 25120683 TI - Undifferentiated embryonal sarcoma of the liver mistaken for hepatic abscess in an adult. AB - Undifferentiated embryonal sarcoma of the liver (UESL) predominantly occurs in children under the age of 10 years, and ~90% of cases occur in children <15 years old. Patients may complain of abdominal pain, fever or other symptoms. No significant decrease has been identified in the hepatic function or elevation of alpha-fetoprotein, which differentiates UESL from primary carcinomas of the liver. In the present study, a rare and misdiagnosed case of an UESL arising in a male, which was mistaken for a hepatic abscess and retrospectively re-diagnosed, is reported. This case was misdiagnosed as a hepatic abscess initially, and it was diagnosed as UESL subsequent to performing tests, including a type-B ultrasonic scan and computed tomography (CT), and evaluating pathological findings. The rapid recurrence of the tumor in this patient was identified by CT, and this is associated with the malignancy of the disease. Currently, patients with UESL have a poor prognosis as there is not a successful treatment strategy. The present study analyzes the course of diagnosis and potential treatment for the disease. PMID- 25120684 TI - Ovarian steroid cell tumor, not otherwise specified: A rare case of postmenopausal vaginal bleeding. AB - Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS) are particularly rare ovarian tumors, which are composed of steroid-hormone secreting cells. The majority of patients with this tumor produce excessive quantities of testosterone and virilization is common. The current report presents a rare case of SCT in a 59-year-old female who presented with postmenopausal vaginal bleeding. The patient had experienced irregular vaginal bleeding for two months, 12 years after menopause. Transvaginal ultrasound and magnetic resonance imaging identified a solid adnexal mass and the pathological result of diagnostic curettage showed a proliferative endometrium. The patient's serum estrogen and testosterone levels were elevated (393.71 nmol/l and 22.28 nmol/l, respectively). The patient underwent an exploratory laparotomy, hysterectomy and bisalpingectomy. The neoplasm was well-circumscribed, solid, homogeneous and yellow in color. Microscopically, the tumor was predominantly composed of granular eosinophilic or vacuolated cytoplasm. Reinke's crystals, prominent nucleoli and Call-Exner bodies were not observed, and there was no mitotic figure. Immunohistochemistry demonstrated that the tumor cells were strongly positive for inhibin. The present rare case aims to expand the current knowledge of this type of ovarian tumor. PMID- 25120685 TI - Expression of Kin17 promotes the proliferation of hepatocellular carcinoma cells in vitro and in vivo. AB - Kin17 protein is ubiquitously expressed in mammals and is correlated with vital biological functions. However, little is known about the role of Kin17 in the proliferation of hepatocellular carcinoma cells. The aim of the present study was to investigate whether the upregulation of Kin17 can promote the growth of hepatocellular carcinoma cells. A series of assays was performed to study the effect of Kin17 in the proliferation of hepatocellular carcinoma cells in vitro and in vivo. The western blotting results revealed that Kin17 expression was increased in hepatocellular carcinoma tissues compared with that of the corresponding normal tissues. Moreover, ectopic upregulation of Kin17 expression promoted the growth of hepatocellular carcinoma cells in vitro and in vivo. These results indicated that Kin17 is involved in the tumorigenesis of hepatocellular carcinoma, and that Kin17 has the potential to serve as a therapeutic target for hepatocellular carcinoma. PMID- 25120686 TI - B7-H3 and B7-H1 expression in cerebral spinal fluid and tumor tissue correlates with the malignancy grade of glioma patients. AB - The B7 family consists of activating and inhibitory molecules that regulate immune responses. Recent research demonstrated the roles of soluble B7-H3 (sB7 H3) and soluble B7-H1 (sB7-H1) in the blood serum of various tumors; however, none of these studies investigated the expression of these proteins in the cerebral spinal fluid (CSF) and blood serum of patients with glioma. The aim of the present study was to investigate the expression of B7-H3 and B7-H1 in the CSF, blood serum and tissues of patients with glioma and their correlation with clinicopathological data. Between January 2012 and November 2012, samples were obtained from 78 patients with glioma, four CSF samples were obtained from patients with a moderate traumatic brain injury, four brain tissue samples were obtained from patients with a traumatic brain injury and 40 blood serum samples were obtained from healthy individuals. The expression of B7-H3 and B7-H1 in the CSF, blood serum and tumor samples of the patients with high-grade glioma was found to be higher than that in the patients with low-grade glioma. However, no significant differences in sB7-H3 and sB7-H1 expression were observed in the blood serum of the patients with glioma compared with the healthy control subjects. In addition, the expression of sB7-H3 and sB7-H1 in the CSF of the patients with glioma was higher than that in the CSF of the patients with a moderate traumatic brain injury. Furthermore, in the patients with glioma, B7-H3 and B7-H1 expression in the CSF and tumor tissue, although not in the blood serum, correlated with the glioma grade. PMID- 25120687 TI - Dermatofibrosarcoma protuberans of the breast: A case report. AB - Dermatofibrosarcoma protuberans (DFSP) is a rare, metastasizing tumor of the deep dermis and subcutaneous tissue. While it frequently occurs in the trunk and extremities, breast involvement has rarely been reported. In the present case, imaging and pathological technologies were used to detect DFSP of the breast. Surgical excision with wide margins (>3 cm) and pathology revealed spindle cells arranged in storiform patterns and short fascicles which were crucially CD34 positive, enabling a definitive diagnosis prior to surgery. PMID- 25120688 TI - Breast cancer metastasis to the stomach confirmed using gastroscopy: A case report. AB - Breast cancer metastasis to the stomach is relatively rare. Unlike infiltrating ductal carcinoma, invasive lobular carcinoma (ILC) has a high tendency to metastasize to the stomach. The present study reports a case of a 53-year-old female who had undergone a modified radical mastectomy of the left breast for ILC eight years previously and presented at the clinic seeking treatment for epigastric discomfort from sour regurgitation and belching that had persisted for one month. Gastroscopy revealed multiple apophysis lesions in the stomach, which were diagnosed as metastatic tumors to the stomach. The diagnosis was further established using histological and immunohistochemical analyses for gross cystic disease fluid protein-15, cytokeratin (CK) 7 and CK20. The patient was treated with systemic chemotherapy without surgery. During the treatment, two gastroscopy procedures revealed that the apophysis lesions in the gastric body had narrowed significantly. Few cases of breast cancer metastasizing to the stomach have been reported, particularly those that have been confirmed using gastroscopy. The present study reports a case of breast cancer metastasis to the stomach to raise awareness of the condition. PMID- 25120690 TI - Progression of penile cutaneous horn to squamous cell carcinoma: A case report. AB - The current report presents the case of a 43-year-old male suffering from a penile cutaneous horn. A surgical excision of the lesion was performed and histopathology demonstrated hyperkeratosis, dyskeratosis and epithelial hyperplasia. The cutaneous horn progressed to squamous cell carcinoma <1.5 months following surgery and a partial penectomy was conducted. The International Index of Erectile Function 5 questionnaire was used to assess the patient and the score had decreased in the one-month postoperative follow-up compared with that of the preoperative period. These findings indicate that undergoing a partial penectomy on initial diagnosis of a penile cutaneous horn should be considered in order to conserve a greater quantity of the penile tissue and improve the postoperative quality of life. PMID- 25120689 TI - Sarcomatoid carcinoma of the renal pelvis: A case report. AB - Sarcomatoid carcinoma is a high-grade malignant neoplasm which exhibits morphological and/or immunohistochemical evidence of bidirectional epithelial and mesenchymal differentiation. Sarcomatoid carcinoma occurring in the upper urinary tract is rare. The present study reports a case of primary sarcomatoid carcinoma of the renal pelvis. A 49-year-old female patient was admitted to Beijing Chao Yang Hospital for experiencing two weeks of intermittent hematuria. A computed tomography scan revealed a mass of 2 cm in diameter in the left renal pelvis. A retroperitoneoscopic nephroureterectomy combined with a bladder cuff excision was performed, and the final pathological diagnosis was sarcomatoid carcinoma of the renal pelvis. The patient did not receive systemic chemotherapy and radiotherapy. Regular follow-up was performed for 30 months, and there was no evidence of tumor local recurrence or distant metastasis. PMID- 25120691 TI - Metastasis of mesothelioma to the maxillary gingiva. AB - Malignant mesothelioma predominantly arises from the serosal surfaces of the pleural or peritoneal cavity. There is currently no effective standard treatment for mesothelioma and the prognosis for patients is poor; the majority of patients with malignant mesothelioma succumb between 12 and 17 months following diagnosis. The association of all forms of malignant mesothelioma with asbestos exposure has been well documented. However, metastasis to the oral gingiva is rare, as only four cases have previously been reported; two cases of metastasis to the tongue and four cases to the jaw bone. In the current report, the case of a 62-year-old male with metastatic mesothelioma is presented. To the best of our knowledge, this is the first report regarding the metastasis of this type of neoplasm to the maxillary gingiva. PMID- 25120692 TI - Biological characteristics of prostate cancer cells are regulated by hypoxia inducible factor 1alpha AB - Hypoxia-inducible factor (HIF)-1alpha has been reported to be associated with malignancy in a number of types of cancer. However, the role of HIF-1 alpha in the regulation of prostate cancer (PCa) growth has yet to be elucidated. The present study aimed to investigate the effect of HIF-1alpha on the biological characteristics of the PCa PC3 cell line. Full-length (fL) HIF-1alpha and dominant-negative (dn) HIF-1alpha were transfected into PC3 cells. The expression of HIF-1alpha and its downstream genes, including vascular endothelial growth factor (VEGF), erythropoietin (EPO) and CXC chemokine receptor 4 (CXCR4), were detected using western blot analysis. Cell proliferation, apoptosis and migration were assessed using MTT, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Boyden chamber assays. The expression of VEGF, EPO and CXCR4 was found to be upregulated in the fL HIF-1alpha-transfected PC3 cells and downregulated in the dn HIF-1alpha-transfected PC3 cells. The overexpression of HIF-1alpha was observed to enhance cell proliferation and migration and decrease docetaxol-induced cell apoptosis. However, dn HIF-1alpha was found to attenuate cell proliferation and migration, and promote docetaxol-induced cell apoptosis. These findings indicate that HIF-1alpha regulates the proliferation, apoptosis and migration of PC3 cells, at least in part, by regulating the expression of its target genes, including VEGF, EPO and CXCR4. Thus, the use of HIF-1alpha inhibitors may be a promising therapy for the treatment of PCa. PMID- 25120693 TI - XRCC2 rs3218536 polymorphism decreases the sensitivity of colorectal cancer cells to poly(ADP-ribose) polymerase 1 inhibitor. AB - Single nucleotide polymorphisms (SNPs) are associated with the development of certain types of cancer. The present study aimed to investigate the association between X-ray repair complementing defective repair in Chinese hamster cells 2 (XRCC2) SNPs and colorectal cancer (CRC) cell sensitivity to the poly(ADP-ribose) polymerase (PARP) 1 inhibitor olaparib (AZD2281). SNaPshot(r) analysis of XRCC2 SNPs was performed in five CRC cell lines. The AZD2281-sensitivities of the CRC cells were also analyzed using MTT assays. The effect of AZD2281 on XRCC2 and PARP1 expression was investigated in the five cell lines using quantitative polymerase chain reaction and western blot analyses. Parallel investigations were performed using a cisplatin (DDP) model of DNA damage. The XRCC2 rs3218536 SNP was found to be associated with the LoVo microsatellite instability CRC cell line. The relative rate of growth inhibition was found to be lower in the LoVo cells following treatment with AZD2281 compared with the other four cell lines (P=0.002). Furthermore, the XRCC2 mRNA level in the LoVo cells was observed to be significantly higher than that in the other four cell lines (P<0.05). Similar results were found using the DDP model of DNA damage (P<0.05). The present study indicated that the XRCC2 rs3218536 polymorphism decreases the sensitivity of CRC cells to AZD2281. PMID- 25120696 TI - Laparoscopic radiofrequency ablation-assisted enucleation of Xp11.2 translocation renal cell carcinoma: A case report. AB - The current study presents a case of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) in a 30-year-old female. The patient was referred to The Affiliated Drum Tower Hospital of the Medical College of Nanjing University (Nanjing, Jiangsu, China) due to a right renal tumor without evident symptoms, which was found by a routine physical examination. A computed tomography (CT) scan indicated that the mass exhibited cystic and solid components. The patient underwent laparoscopic radiofrequency ablation-assisted enucleation. Immunohistochemistry revealed intense nuclear staining for transcription factor E3 protein in the cancer cells. The patient was diagnosed with Xp11.2 RCC. The urological and radiological outcomes remained satisfactory after >2.5 years of follow-up. PMID- 25120695 TI - Conservative management of endometrial stromal sarcoma at stage III: A case report. AB - Endometrial stromal sarcoma (ESS) is a rare malignant tumor of the uterus. The standard treatment is surgery, such as total hysterectomy with bilateral salpingo oophorectomy. The use of adjuvant treatment, including chemotherapy, radiation therapy and endocrine therapy, remains controversial, so it is uncommon for conservative management to be performed in patients with low-grade ESS. The present study reports the case of a 19-year-old female with ESS at stage III who underwent a local mass resection by laparoscopic surgery. A high dose of progestin (medroxyprogesterone acetate) therapy was then administered. Conservative management resulted in complete remission of the low-grade ESS, with no sign of recurrence at the 33-month follow-up. PMID- 25120694 TI - Implications of PPPDE1 expression in the distribution of plakoglobin and beta catenin in pancreatic ductal adenocarcinoma. AB - Human PPPDE peptidase domain-containing protein 1 (PPPDE1) is a recently identified protein; however, its exact functions remain unclear. In our previous study, the PPPDE1 protein was found to be decreased in certain cancer tissues. In the present study, a total of 96 pancreatic ductal carcinoma tissue samples and 31 normal tissues samples were assessed to investigate the distribution of plakoglobin and beta-catenin under the conditions of various PPPDE1 expression levels by means of immunohistochemistry. Generally, the staining of PPPDE1 was strong in normal tissues, but weak in cancer tissues. Plakoglobin was mainly distributed along the membrane and cytoplasm border in normal cells, but was less evident in the membranes of cancer cells. In particular, a greater percentage of cells exhibited low membrane plakoglobin expression in cancer tissue with low PPPDE1 expression (PPPDE1-low cancer) compared with that in cancer tissue with high PPPDE1 expression (PPPDE1-high cancer). The distribution of beta-catenin in normal tissues was similar to that of plakoglobin. However, beta-catenin was peculiarly prone to invade nucleus in PPPDE1-low cancer compared with PPPDE1-high cancer. Our data suggested potential links between PPPDE1 expression and the distribution of plakoglobin and beta-catenin in pancreatic ductal adenocarcinoma, providing insights into the role of PPPDE1 in the progression of pancreatic cancer. PMID- 25120697 TI - Osteosarcoma arising from the parapharyngeal space: A case report. AB - The current study presents a rare case of osteoblastic osteosarcoma arising from an extremely rare site, namely, the parapharyngeal space. To the best of our knowledge, this is the first study of computed tomography (CT) and magnetic resonance imaging (MRI) of an osteosarcoma in the parapharyngeal space with pathological correlation. A 56-year-old male presented with a mass of the right facial region. CT and MRI showed a heterogeneous mass, with ossification or calcification, occupying the parapharyngeal space. Open biopsy revealed an osteoblastic osteosarcoma containing calcified malignant osteoid. Lung CT also showed multiple lung metastases at the time of the first visit to the Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine (Osaka, Japan). Systemic chemotherapy and radiotherapy were administered to the patient for palliation. The patient was alive at the 24-month follow-up subsequent to this treatment. Although a definitive diagnosis requires the use of a biopsy, the CT and MRI findings described in the present study suggest inclusion of this rare tumor in the differential diagnosis that is formed when such findings occur in the parapharyngeal space. The present study also briefly discusses osteosarcoma of the parapharyngeal space. PMID- 25120698 TI - Traumatic breast transposal to the abdominal wall: A case report. AB - Although abdominal wall masses are commonly observed in clinical practice, traumatic breast transposal appearing as an abdominal wall mass is a rare event. The unique phenomenon of a post-traumatic breast growing healthily in the abdominal wall has never previously been reported. The current study presents the case of a 40-year-old female who developed an unusually transposed, but healthy mammary gland in the right upper abdominal wall following a severe pedestrian traffic accident. In that accident, the powerful impact of the car caused multiple right-sided rib fractures, lung injuries and a protruding mass on the right abdominal wall. This sudden onset protruding mass was indicated to be breast tissue by computed tomography imaging and ultrasound scanning. The transposed mammary gland was resected and a pathological examination confirmed that it consisted of normal breast tissue. In this case, the force of the car caused no significant damage or necrosis to the right breast, but instead was sufficient to shift the mammary gland to the abdomen, where it grew healthily 6 months in its new location. This case highlights the capability of the mammary gland to withstand a powerful impact and survive. Moreover, it advances our knowledge of how mammary tissues respond to severe blunt-force impacts. PMID- 25120703 TI - Primary intraosseous carcinoma arising from an odontogenic cyst: A case report. AB - Cyst-like lesions in the mandible rarely develop into malignancies, and the reported incidence is between 0.3 and 2%. The present study describes a rare case of primary intraosseous squamous cell carcinoma of the mandible arising from an odontogenic cyst. A 59-year-old female was referred to Asahi University Murakami Memorial Hospital (Gifu, Japan), with acute pain in the right molars. An initial examination revealed buccal swelling and paresthesia of the mental nerve. Following an intraoral examination, the oral mucosa was confirmed to be normal, however, percussion pain was experienced between the lower right first premolar and second molar. Panoramic radiography revealed a retained lower right wisdom tooth and an irregular radiolucent area between the lower right molar and a mandibular angle with unclear margins. Computed tomography revealed diffuse bone resorption and an extensive loss of cortical bone on the buccal and lingual sides. A biopsy was performed and the pathological diagnosis was of a squamous cell carcinoma arising from the epithelial lining of the odontogenic cyst. Radical dissection was subsequently performed, however, histopathological examination of the resected specimen revealed neither invasion into the surrounding tissues penetrating the periosteum nor lymph node metastasis at the right submandibular lesion. Following the pathological diagnosis of primary intraosseous carcinoma (PIOC), the patient received 6,000 Gy radiation as post operative radiotherapy and chemotherapy with oral administration of tegafur, gimeracil and oteracil potassium. The patient is currently undergoing follow-up examinations. Although PIOC arising from an odontogenic cyst is rare, it should be considered as a differential diagnosis for radiolucency of the jaw bone, particularly in older patients exhibiting a history of cystic lesions. PMID- 25120705 TI - Primary neuroendocrine small cell carcinoma of the parotid gland: A case report and review of the literature. AB - Small cell carcinoma (SCC) is a malignant epithelial tumor that predominantly arises in the lungs. Primary SCC of the parotid gland is rare and difficult to diagnose by analysis of frozen sections obtained during surgery. Due to the aggressive nature of SCC and the frequent occurrence of distant metastases, identification of the disease is important. The current study reports the case of a male patient who presented with a right parotid gland mass. The tumor was resected and evaluated by light microscopy and immunohistochemical analysis. Immunohistochemically, the tumor was positive for cytokeratin, epithelial membrane antigen, cluster of differentiation 117, synaptophysin and thyroid transcription factor-1, which indicated that the tumor was a SCC of the parotid gland. An extended resection of the right parotid gland mass and dissection of the facial nerve were performed. Following discharge from the hospital, the patient received radiation therapy postoperatively. The patient has remained disease free during five months of follow-up. PMID- 25120699 TI - Giant primary cystic mediastinal lymphangioma: A case report. AB - Cystic lymphangioma mainly occurs in children. Cystic mediastinal lymphangioma (CML) originates from mediastinal tissues and is an extremely uncommon cystic lymphangioma that develops from the lymphatic vessels. The present study reports the case of 46-year-old male patient with a giant CML that was surgically resected by video-assisted thoracoscopy. The largest diameter of the CML was 18.0 cm, and ~400 ml of pale yellow fluid was removed from the cystic cavity during surgery. The postoperative pathological reports on the cystic wall showed that the neoplasm was a CML. At present, at the one-year postoperative follow-up, there are no signs of recurrence. In conclusion, complete surgical resection may prevent recurrence. PMID- 25120702 TI - Isolated duodenal myeloid sarcoma associated with the CBFbeta/MYH11 fusion gene followed by acute myeloid leukemia progression: A case report and literature review. AB - Myeloid sarcoma (MS) is a rare disease that presents as an extramedullary tumorous mass of immature myeloid precursors. The majority of MS are identified in acute myeloid leukemia (AML) patients and rarely present as a primary isolated MS without AML. In addition, inversion of chromosome 16 [inv(16)] and the CBFbeta/MYH11 fusion gene are rarely associated with MS. The current study reports a female patient with an isolated duodenal MS, who developed AML-M4 associated with the CBFbeta/MYH11 fusion gene and 48,XX,inv(16),+13,+22. A review of previously reported cases of isolated MS with the CBFbeta/MYH11 fusion gene was also performed. Isolated MS with the CBFbeta/MYH11 fusion gene was often observed in abdominal lesions, with the intestinal tract being the predominantly involved site. In addition, patients with isolated MS with the CBFbeta/MYH11 fusion exhibited a high risk of developing systemic AML. The diagnosis of isolated MS may be particularly challenging and, therefore, determining the optimal standard treatment for isolated MS is required. PMID- 25120701 TI - Association between four common microRNA polymorphisms and the risk of hepatocellular carcinoma and HBV infection. AB - microRNAs (miR/miRNAs) have been demonstrated to function as tumor suppressors and oncogenes, and miRNA polymorphisms may have a role in cancer development. The present study aimed to investigate the association between the miR-146aG>C, miR 149C>T, miR-196a2C>T and miR-499A>G polymorphisms and the risk of hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) infection. A total of 271 patients with HCC and 532 healthy control participants were enrolled in the present study. miR-146aG>C, miR-149C>T, miR-196a2C>T and miR-499A>G polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. A significant difference was identified in the genotype frequency of miR 196a2C>T in the patients in the case group compared with the control group (chi2=6.88; P=0.032). Compared with the CC genotype, the miR-196a2 TT genotype was associated with a significantly reduced risk of HCC [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.38-0.99], and a significantly reduced risk was also found in the dominant (OR, 0.69; 95% CI, 0.49-0.98) and recessive (OR, 0.70; 95% CI, 0.46-1.02) models. Moreover, individuals with HBV who were carrying the miR-196a2 CT and TT genotypes had a significantly reduced risk of HCC (OR, 0.62; 95% CI, 0.41-0.95; and OR, 0.39; 95% CI, 0.20-0.73, respectively). In conclusion, the present study found that the miR-196a2C>T polymorphism has a protective effect in patients with HCC, particularly in those with HBV infection. PMID- 25120700 TI - Mutation analysis of key genes in RAS/RAF and PI3K/PTEN pathways in Chinese patients with hepatocellular carcinoma. AB - The RAS/RAF and PI3K/PTEN signaling pathways play central roles in hepatocarcinogenesis. KRAS, NRAS, HRAS, BRAF, PIK3CA, PIK3R1 and PTEN are key cancer-related genes in the RAS/RAF and PI3K/PTEN signaling pathways. Genetic alterations in these genes often lead to the dysregulation of the two cascades. Little is known regarding the frequency of hotspot mutations in these critical components among Chinese patients with hepatocellular carcinoma (HCC). In the current study, 57 somatic hotspot mutations in 36 HCCs samples collected from Chinese patients using direct DNA sequencing method were examined. Two cases of KRAS somatic mutations (KRAS codon 61; Gln to His) were identified among 36 HCCs (5.6%). However, no mutations were found in the NRAS, HRAS, BRAF, PIK3CA, PIK3R1 and PTEN genes. These findings indicated that point mutations in the KRAS gene, but not mutations in NRAS, HRAS, BRAF, PIK3CA, PIK3R1 and PTEN genes, at a somatic level contribute to the abnormal activation of the RAS/RAF and PI3K/PTEN pathways in HCC. PMID- 25120704 TI - Metformin inhibits the proliferation of A549/CDDP cells by activating p38 mitogen activated protein kinase. AB - Metformin (Met) has been widely used in hypoglycemic therapy, and it is also able to reduce the incidence of tumors and tumor-related mortality. The present study investigated whether Met could inhibit the proliferation of lung cancer cells and enhance the sensitivity of a cisplatin-resistant lung cancer A549/CDDP cell line to cisplatin. It was found that Met treatment inhibited the proliferation of different lung cancer cells. Met inhibited the cell cycle of the A549/CDDP cells and induced apoptosis. Upon Met treatment, the A549/CDDP cells were arrested at the G1 phase. The apoptosis of the A549/CDDP cells was confirmed by the appearance of apoptotic bodies in cells stained with Hoechst 33258, and by the cleavage of BH3 interacting-domain death agonist and poly (ADP-ribose) polymerase. Furthermore, results showed that the phosphorylation level of p38 mitogen-activated protein kinase (MAPK) was increased after Met treatment. The p38 MAPK inhibitor, SB203580, significantly blocked Met-induced apoptosis in the A549/CDDP cells. It was further demonstrated that Met could enhance the sensitivity of the A549/CDDP cells to cisplatin. In summary, the present study identified Met as a drug sensitizer that could improve the treatment effect of cisplatin in cisplatin-resistant lung cancers. PMID- 25120706 TI - Ovarian hyperstimulation in premenopausal women during adjuvant tamoxifen treatment for endocrine-dependent breast cancer: A report of two cases. AB - Adjuvant endocrine therapy is an integral component of care for endocrine dependent breast cancer. The aim of this type of therapy is to counteract the production and the action of estrogens. The ovary is the primary site of estrogen production in premenopausal women, whereas, in postmenopausal women, the main source of estrogens is adipose tissue. Therefore, ovarian function suppression is an effective adjuvant strategy in premenopausal estrogen-dependent breast cancer. Similarly, the inhibition of estrogen action at the receptor site by tamoxifen has proven to be effective. To date, international consensus statements recommend tamoxifen (20 mg/day) for five years as the standard adjuvant endocrine therapy for premenopausal women. It should be noted that tamoxifen is a potent inducer of ovarian function and consequent hyperestrogenism in premenopausal women. In the present study, we report two cases of ovarian cyst formation with very high estrogen levels and endometrial hyperplasia during the administration of tamoxifen alone as adjuvant treatment for estrogen receptor-positive breast cancer in premenopausal women. These cases suggest that in young premenopausal patients with estrogen-dependent breast cancer, ovarian suppression is an essential prerequisite for an adjuvant endocrine therapy with tamoxifen. In this context, luteinizing hormone-releasing hormone agonist treatment by suppressing effective ovarian function may lead to a hypoestrogenic status that may positively impact breast cancer prognosis and prevent the effects of tamoxifen at the gynecological level. It is important to reconsider the action of tamoxifen on ovarian function and include these specific effects of tamoxifen in the informed consent of premenopausal patients who are candidates for tamoxifen alone as adjuvant endocrine treatment. PMID- 25120707 TI - Oral malignant melanoma: A report of two cases with BRAF molecular analysis. AB - Primary oral malignant melanoma is a rare condition, accounting for 1.3-1.4% of all melanomas, usually presenting with an aggressive clinical behavior. The present study reports the clinicopathological findings of two cases of oral malignant melanoma and discusses the epidemiology, diagnosis and current therapeutic approaches for this uncommon condition. In the first case the patient presented with a pigmented lesion located on the lower mucosal lip. The patient showed no nodal metastases and therefore, underwent a wedge resection. After seven months, the patient presented with neck lymph nodes and multiple visceral metastases. Molecular analysis of BRAF, using a pyrosequencing approach, revealed the presence of BRAF V600E mutation. The patient developed multiple visceral metastases, but refused treatment and was lost to follow-up. In the second case, no BRAF V600E mutation was found, but the patient exhibited a pigmented patch in the lower gingival mucosa, which was excised by surgical treatment. The patient was followed up by an oncologist, but did not undergo an additional therapy and is currently alive with no evidence of visceral metastases at one year following the diagnosis. PMID- 25120708 TI - Basaloid squamous cell carcinoma of the maxillary gingiva: A case report and review of the literature. AB - Basaloid squamous cell carcinoma (BSCC) is a rare, but distinct histologic variant of squamous cell carcinoma in the head and neck region. It is considered to have a poor prognosis due to its aggressive behavior and tendency to metastasize. The usual sites of BSCC are the floor of the mouth, hypopharynx and base of the tongue, and according to the English-language literature its presentation in the gingiva is somewhat uncommon. In the current report, the unusual case of a 40-year-old male is presented; the patient exhibited a painless irregular mass in the maxillary gingiva, which infiltrated the maxillary sinus, as observed by computed tomography. Hematoxylin and eosin-stained sections revealed a diagnosis of BSCC with typical central necrosis in the cancer nests, which contained basaloid and squamous cells. Immunohistochemistry revealed that p63 was weakly positive, high molecular weight cytokeratin (CK) was focally positive, and S-100, CK7, CK14 and vimentin were negative. It must be noted that histopathology results may be incorrectly interpreted as adenoid cystic carcinoma, undifferentiated carcinoma and basal cell adenocarcinoma. PMID- 25120709 TI - Meningeal myofibroblastoma in the frontal lobe: A case report. AB - Myofibroblastoma is a benign tumor composed of spindle cells in clusters and fascicles. To date, only three cases of intracranial myofibroblastoma have been reported. The present study reports the case of a 47-year-old female with meningeal myofibroblastoma. The patient had a history of ovarian cyst resection and presented with paroxysmal mild headaches that had been apparent for 4 years. Magnetic resonance imaging disclosed a well-circumscribed mass in the left frontal lobe. A resection of the mass was performed. Abundant fascicular clusters of spindle- and oval-shaped cells were found by conventional histopathology. Immunohistochemical staining demonstrated that these cells were strongly positive for smooth muscle actin, weakly positive for epithelial membrane antigen and negative for cluster of differentiation (CD)117, CD34, S-100 or desmin, with a Ki 67 index of >10%. These results supported the diagnosis of myofibroblastoma. No recurrence of the mass was found during the 24-month follow-up period. Overall, the patient exhibited a rare type of meningeal neoplasm. Resection of the tumor proved to be successful and no recurrence were found. Histopathological and immunohistochemical staining is crucial to form a diagnosis. To the best of our knowledge, the present study is the first to show the presence of myofibroblastoma in the left frontal lobe. PMID- 25120710 TI - Icotinib inhibits the invasion of Tca8113 cells via downregulation of nuclear factor kappaB-mediated matrix metalloproteinase expression. AB - Icotinib is an epidermal growth factor receptor tyrosine kinase inhibitor, which has been revealed to inhibit proliferation in tumor cells. However, the effect of icotinib on cancer cell metastasis remains to be explained. This study examines the effect of icotinib on the migration and invasion of squamous cells of tongue carcinoma (Tca8113 cells) in vitro. The results of the Boyden chamber invasion assay demonstrated that icotinib reduced cell invasion, suppressed the protein levels of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, and increased the expression of tissue inhibitor of metalloproteinase-1. In addition, icotinib was found to significantly decrease the protein levels of nuclear factor kappaB (NF kappaB) p65, which suggested that icotinib inhibits NF-kappaB activity. Furthermore, treatment with the NF-kappaB inhibitor, pyrrolidine dithiocarbamate, suppressed cell invasion and MMP-2 expression. These results suggested that icotinib inhibits the invasion of Tca8113 cells by downregulating MMP via the inactivation of the NF-kappaB signaling pathways. PMID- 25120711 TI - Late-onset sarcoidosis in a patient with gastric mucosa-associated lymphoid tissue non-Hodgkin lymphoma: A case report. AB - The simultaneous presence of hematological malignancies and sarcoidosis, defined as sarcoidosis-lymphoma syndrome, has been reported in 79 patients in the literature to date. The majority of these patients were affected by sarcoidosis and developed non-Hodgkin lymphoma or acute leukemia after 1-2 years; however, in <20 cases the malignancy developed first. This report presents the case of an 83 year-old male with a clinical history of Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma. The patient developed sarcoidosis 10 years after the first diagnosis, which caused the diagnostic work-up and differential diagnosis between a lymphoma relapse and de novo sarcoidosis to be challenging. PMID- 25120712 TI - Maintenance therapy with capecitabine in patients with locally advanced unresectable pancreatic adenocarcinoma. AB - Therapeutic options for locally advanced pancreatic cancer (LAPC) include concurrent chemoradiation, induction chemotherapy followed by chemoradiation or systemic therapy alone. The original Gastro-Intestinal Study Group and Eastern Cooperative Oncology Group studies defined fluorouracil (5-FU) with concurrent radiation therapy followed by maintenance 5-FU until progression, as the standard therapy for this subset of patients. Although this combined therapy has been demonstrated to increase local control and median survival from 8 to 12 months, almost all patients succumb to the disease secondary to either local or distant recurrence. Our earlier studies provided a strong rationale for the use of capecitabine in combination with concurrent radiation followed by maintenance capecitabine therapy. To report our clinical experience, we retrospectively evaluated our patients who were treated with maintenance capecitabine. We reviewed the medical records of patients with LAPC who received treatment with capecitabine and radiation, followed by a 4-week rest, then capecitabine alone 1,000 mg twice daily (ECOG performance status 2 or age >70 years) or 1,500 mg twice daily for 14 days every 3 weeks until progressive disease. We treated 43 patients between September 2004 and September 2012. The population consisted of 16 females and 25 males, with a median age of 64 years (range, 38-80 years). Patients received maintenance capecitabine for median duration of 9 months (range, 3-18 months). The median overall survival (OS) for these patients was 17 months, with two patients still living and receiving therapy. The 6-month survival rate was 91% (39/43), 1-year survival rate was 72% (31/43) and 2-year OS rate was 26% (11/43). Grade 3 or 4 toxicity was observed rarely: Hand-foot syndrome (HFS) in two patients, diarrhea in one patient and peripheral neuropathy in one patient, and there was no mortality directly related to treatment. Capecitabine maintenance therapy following chemoradiation in LAPC offers an effective, tolerable and convenient alternative to 5-FU. To the best of our knowledge, this is the largest study of its kind which has determined the safety and efficacy of capecitabine maintenance therapy for patients with LAPC. PMID- 25120713 TI - Crosstalk between the p38 and TGF-beta signaling pathways through TbetaRI, TbetaRII and Smad3 expression in plancental choriocarcinoma JEG-3 cells. AB - Choriocarcinoma is a highly aggressive tumor that develops from germ cells. Some choriocarcinomas originate in the testes or ovaries, while others may develop in the uterus after a normal pregnancy or after miscarriage. The tumor is characterized by early hematogenous spread to distal organs, such as the lung and brain. Transforming growth factor beta1 (TGF-beta1) is key in regulating tumor cell proliferation and invasion through a variety of Smad-dependent and independent pathways, including the p38 mitogen-activated protein kinase (MAPK) pathway. There appears to be crosstalk between the TGF-beta/Smad and p38 MAPK pathways; however, the molecular mechanisms underlying the crosstalk are not fully understood. The present study validated the role of TGF-beta signaling in cancer progression and explored the interaction between Smad and p38 MAPK signaling on transduction mediators in choriocarcinoma using the JEG-3 cell line. MTT assay was used to detect the effect of TGF-beta1 on JEG-3 cell proliferation. Cells were treated with p38 MAPK inhibitor and TGF-beta receptor inhibitor, followed by TGF-beta1, and reverse transcription quantitative real-time polymerase chain reaction was used to examine the transcriptional levels of Smad3 and TGF-beta receptors. The data demonstrated that TGF-beta can enhance the viability of JEG-3 cells. Blockade of the TGF-beta and p38 MAPK pathways attenuated the expression of Smad3, TGF-beta receptor type I (TbetaRI) and TbetaRII, and inhibited their expression in a dose-dependent manner. Analysis revealed that p38 MAPK is involved in and contributes to the TGF-beta pathway, dependent on the regulation of TbetaRI, TbetaRII and Smad3. Further investigation of the interactions between the TGF-beta and p38 MAPK pathways may offer potential venues for therapeutic intervention for choriocarcinoma. PMID- 25120715 TI - Laparoscopic liver biopsy in the diagnosis of hepatic epithelioid hemangioendothelioma: A case report. AB - Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver, and its definitive diagnosis is completely dependent on histopathological verification. In the present study, we report the case of a patient whose percutaneous liver biopsy failed to reveal a diagnosis of HEH, twice, and who was ultimately diagnosed by laparoscopic liver biopsy. The patient was a 42-year-old female with mild right upper quadrant discomfort. Ultrasonography and magnetic resonance imaging showed multiple mass lesions scattered throughout the liver, but no evidence of extrahepatic diseases. The initial laboratory tests included liver function tests and tumor markers were within normal limits. Subsequently, two, ultrasound (US)-guided liver biopsies from the liver lesion were performed using an 18-gauge needle, and both of these showed massive hepatocellular necrosis. To obtain adequate tissue samples for histological examination, the patient underwent laparoscopic liver biopsy. The overall immunohistochemical findings supported the diagnosis of HEH. In the present case, two, US-guided percutaneous liver biopsies failed to diagnose HEH, and laparoscopic liver biopsy was safely performed to obtained adequate specimens for analysis. Although this method is not the preferred technique and has certain disadvantages, it is considered to be a useful and minimally invasive approach for liver lesions when other less-invasive diagnostic modalities fail or are difficult to be performed. PMID- 25120714 TI - Tracheal adenoid cystic carcinoma mimicking a thyroid tumor: A case report. AB - At present, only eight cases of tracheal adenoid cystic carcinomas (ACCs) mimicking thyroid tumors have been reported. Since there are no guidelines available regarding their diagnosis and treatment, they present a significant clinical challenge. In the present study, patient treatment was analyzed to deliver the first concise summary of treatment options in patients with ACC mimicking a thyroid tumor. In addition, all available data regarding molecular abnormalities of this disease have been discussed. The current study presents a case of a 17-year-old patient with a tracheal ACC mimicking a thyroid tumor. The patient was diagnosed in 2007 with a pathological mass between the left lobe of the thyroid and the trachea, and underwent surgery and radiotherapy. In 2010, multiple lesions in the lungs were diagnosed and pulmonary metastasectomy was performed. Following surgery, the patient has been disease-free for almost 30 months. Thyroid tumor biopsy may reveal ACCs. This pathological report requires further investigation of the head and neck in order to confirm if the disease is of tracheal origin. Patients may present with a neck swelling, hoarseness of voice or dysphagia. Surgery must be considered as first-line therapy for all patients with local disease as it may be curative. For palliative treatment chemoradiotherapy based on cisplatin may be effective. The identification of cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations and mitochondrial abnormalities specific for ACCs is critical to the development of targeted therapies. Thus far, large studies have only reported the transcriptional activator Myb and mammalian target of rapamycin signaling pathway to be disrupted in ACCs. PMID- 25120716 TI - High efficacy of gefitinib in the treatment of EGFR mutation-positive advanced non-small cell lung adenocarcinoma: A case report. AB - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, are known to play a significant role in EGFR mutation positive non-small cell lung cancer. When an EGFR mutation is found, gefitinib and erlotinib have been shown to have significant roles in the treatment of untreated advanced NSCLC. This study reports an EGFR mutation in NSCLC treated with gefitinib and is notable due to the patient's marked improvement following a shorter than average duration of treatment with gefitinib. The present study reports the case of a 58-year-old male smoker with a dry cough. Computed tomography revealed a mass in the left inferior lobe of the lung. The patient was subsequently diagnosed with advanced lung adenocarcinoma, and an EGFR mutation (in-frame deletions of E746-A750 in exon 19) was found. The patient received multiple rounds of chemotherapy, followed by gefitinib maintenance therapy for 3 months. Later on, a grade 1 acne-like rash developed on the face and back that lasted throughout the treatment. Currently, the patient is stable, with no evidence of disease progression. The present study describes the disease and the treatment using gefitinib. PMID- 25120717 TI - Cathepsin D serum and urine concentration in superficial and invasive transitional bladder cancer as determined by surface plasmon resonance imaging. AB - Determination of cathepsin D (Cat D) concentration in serum and urine may be useful in the diagnosis of bladder cancer. The present study included 54 healthy patients and 68 patients with bladder cancer, confirmed by transurethral resection or cystectomy. Cat D concentration was determined using a surface plasmon resonance imaging biosensor. Cat D concentration in the serum of bladder cancer patients was within the range of 1.3-5.59 ng/ml, while for healthy donors it was within the range of 0.28-0.52 ng/ml. In urine, the Cat D concentration of bladder cancer patients was within the range of 1.35-7.14 ng/ml, while for healthy donors it was within the range of 0.32-0.68 ng/ml. Cat D concentration may represent an efficient tumor marker, as its concentration in the serum and urine of transitional cell carcinoma patients is extremely high when compared with healthy subjects. PMID- 25120718 TI - A large odontogenic myxoma of the bilateral maxillae: A case report. AB - Odontogenic myxomas (OMs) are benign mesenchymal locally aggressive neoplasms of the jaw bone. Although OMs predominantly involve the mandible, maxillary tumors are usually more aggressive than mandibular tumors. The present study describes the case of a 37-year-old male with a large odontogenic myxoma of the bilateral maxillae, which caused a defect in the right skull base bone. The tumor was successfully removed through radical resection of the hard tissue and local resection around the envelope of the soft tissue. The tumor exhibited no recurrence. However, the current methods for bilateral maxillary reconstruction to restore the maxillary buttress and achieve an optimal aesthetic appearance are complicated due to the lack of suitable conditions for oral rehabilitation with good dentition. PMID- 25120719 TI - Clinical significance of serum soluble death receptor 5 concentration in locally advanced non-small cell lung cancer patients. AB - There is an urgent requirement for the identification of suitable biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). The present study aimed to measure the levels of serum soluble death receptor 5 (sDR5) in patients with locally advanced stage III NSCLC, and to evaluate its diagnostic and prognostic significance in these patients. The sDR5 concentrations were evaluated by the enzyme-linked immunosorbent assay method in 50 healthy controls and 122 patients with locally advanced stage III NSCLC [including 57 adenocarcinoma (ADC) and 65 squamous cell carcinoma (SCC) patients], before and after concurrent chemoradiotherapy. It was found that the pretreatment sDR5 levels in patients with NSCLC were higher than the sDR5 levels of healthy controls (P<0.001). However, no significant difference in the sDR5 levels was observed between the ADC and SCC subgroups (P=0.874). According to multiple clinical classifications, a significant increase in the pretreatment serum sDR5 levels could be observed in IIIB-stage patients compared with IIIA-stage patients (P=0.009). Patients with a tumor burden >3 cm had higher pretreatment sDR5 concentration than those with a tumor burden <=3 cm (P=0.026). Additionally, T4 stage patients had significantly higher pretreatment sDR5 levels compared with those of T1-stage patients (P<0.001). There were no significant differences between pre- and post-treatment sDR5 concentrations in the total NSCLC patient group (P=0.462), ADC subgroup (P=0.066) and SCC subgroup (P=0.052). Furthermore, when patients were divided according to therapeutic response, the pretreatment sDR5 levels in the responder patients were significantly lower compared with those of the non-responders (P<0.001). Further survival analysis showed that the patients whose pretreatment sDR5 levels were <=14 pg/ml (cutoff value, 14 pg/ml) had a longer progression-free survival (PFS) time than patients with sDR5 levels >14 pg/ml. However, no correlation was observed between the post-treatment sDR5 levels and therapeutic response or PFS time. To the best of our knowledge, the present study results provide the first evidence that the pretreatment serum levels of sDR5 may be a useful biomarker for the diagnosis, prediction and prognosis of patients with locally advanced stage III NSCLC. PMID- 25120720 TI - Serum secreted frizzled-related protein 5 levels differentially decrease in patients with hepatitis B virus-associated chronic infection and hepatocellular carcinoma. AB - The aim of this study was to investigate the characteristics of serum secreted frizzled-related protein 5 (SFRP5), an inhibitor of Wnt signaling, in hepatitis B virus (HBV)-associated infections and hepatocellular carcinoma (HCC) patients. Serum SFRP5 levels were detected in 147 patients with HBV-associated chronic infection or HCC. Compared with the non-HBV-infected and non-HCC group, the HBV associated chronic infection and HCC groups exhibited decreased serum SFRP5 levels. A significant inverse correlation between serum SFRP5 levels and HBV DNA levels was identified in the HBV-associated chronic infection and HCC groups. Furthermore, SFRP5 levels differentially decreased in patients with HBV associated diseases, in a manner which was dependent on liver disease status. Compared with patients exhibiting HBV-associated chronic infection, patients with HCC were found to exhibit lower serum SFRP5 levels. The results of the present study indicated that patients with HBV-associated liver infection and HCC exhibited significantly deceased serum SFRP5 levels, which were found to negatively correlate with HBV DNA levels. Serum SFRP5 levels may present a biomarker for the severity of HBV-associated liver infection, and the risk of HCC initiation and progression. PMID- 25120721 TI - Metaplastic breast carcinoma development following surgical resection of an inflammatory myofibroblastic tumor in the right breast: A case report. AB - Inflammatory myofibroblastic tumors (IMTs) are uncommon, mesenchymal lesions, and malignant transformation is extremely rare. The current study presents the case of a 56-year-old female with a rapidly growing mass in the right breast, which was diagnosed as IMT. Immunohistochemically, the mass was positive for smooth muscle actin (SMA) and Ki-67 (positive staining in 30% of the cells), and negative for S-100, cluster of differentiation (CD)34, p63 and cytokeratin. Malignant transformation to metaplastic carcinoma of the spindle-cell type was observed following surgical resection. This metaplastic carcinoma demonstrated positive immunoreactivity for cytokeratin, vimentin, CD34, p63 and Ki-67 (>30%), and was negative for cytokeratin 7, SMA, desmin and S-100. The patient underwent total mastectomy of the right breast, followed by palliative chemotherapy with capecitabine; however, the patient succumbed to the disease after 12 weeks. The unusual case presented in the current study emphasizes the importance of pre operative examinations to determine the benign or malignant nature of IMTs, which aids in the choice of appropriate surgical procedures. PMID- 25120723 TI - 10058-F4, a c-Myc inhibitor, markedly increases valproic acid-induced cell death in Jurkat and CCRF-CEM T-lymphoblastic leukemia cells. AB - Adult T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis. Although it has been found that activation of Notch1 signaling occurs in >50% T-ALL patients, gamma-secretase inhibitors that target Notch1 signaling are of limited efficacy. However, c-Myc is an important direct target of Notch1 and, thus, c-Myc is another potential therapeutic target for T-ALL. Valproic acid (VPA), a histone deacetylase inhibitor, has been reported to treat various hematological malignancies. In the present study, we showed that c-Myc expression, at a transcriptional level, was dose-dependently downregulated in VPA-induced growth inhibition in T-ALL cell lines, Jurkat and CCRF-CEM cells. 10058-F4, a small molecule c-Myc inhibitor, could increase the downregulation of c-Myc and markedly increase the growth inhibition and cell death induced by VPA in Jurkat and CCRF CEM cells, which was accompanied by obvious cleavage of capase-3. Z-VAD-FMK, a caspase inhibitor, partially prevented the anti-leukemic effect. The results of the present study suggest that c-Myc inhibitors increase cell death induced by VPA in a caspase-dependent and -independent manner, and their combination could be a potent therapeutic strategy for adult T-ALL patients. PMID- 25120724 TI - PIN1 promoter polymorphism (-842 G>C) contributes to a decreased risk of cancer: Evidence from meta-analysis. AB - Peptidyl-prolylcis-trans isomerase NIMA-interacting 1 (encoded by the PIN1 gene) regulates the conformation of proline-directed phosphorylation sites and is important in the etiology of cancer. Since the identification of a functional polymorphism of PIN1, (-842 G>C; rs2233678), in the PIN1 promoter region, numerous studies have evaluated the association between the PIN1 promoter polymorphism (-842 G>C) and cancer risk. However, the available results are inconclusive. To derive a more precise estimation, a meta-analysis of seven previous case-control studies was performed, which included 4,524 cases exhibiting different tumor types and 4,561 control subjects. The published literature was retrieved from PubMed and EMBASE. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Overall, the results of the present study demonstrated that individuals carrying the variant C allele (G/C and C/C) were associated with a significantly decreased cancer risk (OR, 0.75; 95% CI, 0.62-0.90 for GC vs. GG; OR, 0.75; 95% CI, 0.64-0.88 for GC/CC vs. GG). In further stratified analyses, a decreased cancer risk was observed in the following subgroups: Breast and lung cancer patients, Asian individuals, and in studies with a sample size >500. The results indicated that the PIN1 promoter polymorphism (-842 G>C; rs2233678) contributes to a decreased risk of cancer via attenuating the transcriptional activity. PMID- 25120722 TI - Synergy of 1,25-dihydroxyvitamin D3 and carboplatin in growth suppression of SKOV 3 cells. AB - 1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] has been demonstrated to inhibit the growth of cancer cells. However, carboplatin is the most widely used chemotherapeutic agent to treat cancer. We hypothesized that vitamin D may enhance the antiproliferative effects of carboplatin, and tested this hypothesis in ovarian cancer SKOV-3 cells treated with carboplatin and 1,25(OH)2D3. Cell viability was determined by Cell Counting Kit-8, while cell cycle distribution, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. In these experiments, 1,25(OH)2D3 and carboplatin each provided dose-dependent suppression of SKOV-3 growth, and synergy was demonstrated between 10 nM 1,25(OH)2D3 and carboplatin. The proportion of cells in G0/G1 phase was markedly reduced by the drug combination, while the proportion of cells in G2/M phase was increased. Apoptosis did not increase in ovarian cancer cells treated with 10 nM 1,25(OH)2D3 alone; however, 1,25(OH)2D3 evidently enhanced carboplatin-induced apoptosis. Similarly, ROS production was evidently higher and MMP was lower in cells treated with the two drugs than in those treated with each drug alone. The results suggested that 1,25(OH)2D3 suppresses SKOV-3 growth and enhances the antiproliferative effect of carboplatin. The drugs function synergistically by inducing cell cycle arrest, increasing apoptosis and ROS production, and reducing MMP. PMID- 25120725 TI - Claudin-4 expression in gastric cancer cells enhances the invasion and is associated with the increased level of matrix metalloproteinase-2 and -9 expression. AB - Claudin-4 is a member of a large family of transmembrane proteins known as claudins, which are essential for the formation and maintenance of tight junctions. Our previous studies have revealed that claudin-4 proteins are overexpressed in metastatic gastric cancer. To clarify the roles of claudin-4 in gastric cancer metastasis, human gastric adenocarcinoma (AGS) cells constitutively expressing wild-type claudin-4 were generated. Expression of claudin-4 in AGS cells was found to increase cell invasion and migration, as measured by Boyden invasion chamber assays. Moreover, the claudin-4-expressing AGS cells were found to have increased matrix metalloproteinase (MMP)-2 and -9 expression, indicating that claudin-mediated increased invasion may be mediated through the activation of the MMP protein. Overall, the results suggest that claudin-4 overexpression may promote gastric cancer metastasis through the increased invasion of gastric cancer cells. PMID- 25120726 TI - Combined treatment of PC-3 cells with ultrasound and microbubbles suppresses invasion and migration. AB - The aim of the present study was to investigate whether ultrasound treatment combined with microbubbles inhibits cell invasion and migration in androgen independent prostate cancer (PCa) cells and to identify the probable mechanism. Ultrasound was used in continuous wave mode at a frequency of 21 kHz and with a spatial-average temporal-average intensity of 46 mW/cm2. Ultrasound combined with microbubbles (200 MUl; SonoVue) was administered to androgen-independent human PCa PC-3 cells for 30 sec. The PC-3 cells were divided into three groups: The control group, the ultrasound group (US) and the ultrasound combined with microbubbles group (US + MB). Following treatment for 12, 24, 48 and 72 h, cell counting kit-8 was used to assess cell viability. Cell invasion and migration was measured 12 h after treatment using Transwell migration assays. Quantitative polymerase chain reaction and western blot analysis were used to evaluate the expression of the migration-associated proteins, matrix metalloproteinase (MMP)-2 and MMP-9. Cell reproduction levels in the US and US + MB groups were significantly suppressed when compared with the control group (P<0.01) following 24 h of treatment and this suppression was significantly higher in the US + MB group than in the US group (P<0.01). However, no significant differences in cell reproduction levels between the three groups were identified at 12 h (P>0.05). Ultrasound combined with microbubbles significantly suppressed the level of invasion and migration in the PC-3 cells compared with the control group (190.83+/-14.63 vs. 509.67+/-18.62, P<0.01; and 86.67+/-10.60 vs. 271.33+/-65.14; P<0.01, respectively). Furthermore, combined treatment with ultrasound and microbubbles suppressed the expression of MMP-2 and MMP-9. In conclusion, it was found that ultrasound combined with microbubbles suppressed invasion and migration in human PCa PC-3 cells via downregulation of MMP-2 and MMP-9. PMID- 25120727 TI - Giant colonic lipoma with prolapse through the rectum treated by external local excision: A case report. AB - Colonic lipomas are a rare type of gastrointestinal benign tumor. Those that are <2 cm are generally asymptomatic and do not require any treatment. However, those that are >2 cm may be symptomatic, resulting in abdominal pain, changes in bowel habits, intestinal obstruction and rectal bleeding. A 39-year-old male patient presented with a mass prolapse through the anal canal, which was causing anal pain and rectal bleeding. The patient was admitted to hospital via the emergency services and directed to the Department of General Surgery with the preliminary diagnosis of a rectal prolapse. A pedunculated polyp (size, 10*8*7.5 cm) was detected at the 35th cm of the anal canal. Due to the large size of the polyp, an endoscopic polypectomy could not be performed. Therefore, the prolapsed lipoma was excised externally and the patient was discharged on the first postoperative day on which no complications were experienced. A colonic lipoma must be considered during the differential diagnosis of anorectal diseases, such as hemorrhoids and rectal prolapses. Local excision, hemicolectomy, and segmental and external resection should be considered in addition to an endoscopic polypectomy for the diagnosis and treatment of colonic lipomas. PMID- 25120728 TI - Intraspinal leiomyoma: A case report and literature review. AB - Leiomyomas are benign tumors which are predominantly found in the genitourinary and gastrointestinal tracts. Leiomyomas in the spine are extremely rare. The current study presents a case of a 35-year-old female with intraspinal leiomyoma who presented with low back pain and weakness in the left leg of two months. Computerized tomography and magnetic resonance imaging revealed an epidural mass at the T11-12 levels. The patient underwent a T11-12 laminectomy through posterior approach, achieving total removal of the tumor with a well-demarcated dissection plane. Pathological examination demonstrated a leiomyoma. Postoperatively, the patient showed a significant improvement in neurological function. Although intraspinal leiomyoma is extremely rare, it should be considered in the differential diagnosis of spinal lesions in females. The diagnosis is predominantly dependent on a pathological examination. Gross total resection is recommended for its treatment, however the prognosis remains poor. Post-operative hormonal therapy may be useful in controlling tumor recurrence. PMID- 25120729 TI - Is apolipoprotein E4 an important risk factor for vascular dementia? AB - Despite the fact that vascular dementia (VaD) represents the seconding leading cause of dementia in the USA, behind only Alzheimer's disease (AD), there remains a lack of consensus on the pathological criteria required for diagnosis of this disease. A number of clinical diagnostic criteria exist but are poorly validated and inconsistently applied. It is clear that vascular risk factors play an important role in the etiology of VaD, including hypertension, stroke, diabetes, and atherosclerosis. Vascular risk factors may increase the risk for VaD by promoting inflammation, cerebral vascular disease, white matter lesions, and hippocampal sclerosis. Because vascular risk factors seem to impart a high degree of risk for conferring VaD, it seems logical that the apolipoprotein E (APOE) status of individuals may be important. APOE plays a critical role in transporting cholesterol in and out of the CNS and in AD it is known that harboring the APOE allele increases the risk of AD perhaps due to the improper functioning of this protein. The purpose of this review is to examine the important pathological features and risk factors for VaD and to provide a critical assessment of the current literature regarding whether or not apoE4 also confers disease risk in VaD. The preponderance of data suggests that harboring one or both APOE4 alleles elevates the risk for VaD, but not to the same extent as found in AD. PMID- 25120730 TI - A focused review of hematopoietic neoplasms occurring in the therapy-related setting. AB - Hematological neoplasms developed in patients with a history of cytotoxic therapies comprise a group of diseases with a poor clinical outcome, and collectively categorized as "therapy-related myeloid neoplasms" (t-MN) in the 2008 World Health Organization (WHO) Classification. In recent years, numerous publications have emerged, and these studies have greatly expanded the scope of our understanding in this field. We here focused our review on several selected areas including secondary malignancies occurring in patients with autoimmune diseases; radiation therapy alone as a causative agent; the similarity and differences between therapy-related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML); clinical behavior and treatment outcome of t-AML patients with favorable cytogenetics; the incidence and clinical features of myelodysplastic/myeloproliferative neoplasms, as well as acute lymphoblastic leukemia and myeloproliferative neoplasms in patients with prior cytotoxic exposure. These recent studies have shown that therapy-related hematopoietic neoplasms are heterogeneous, and may manifest in various forms, more complex than we have recognized previously. Cytogenetic abnormalities and underlying mutations are likely to be the major factors dictating prognosis. PMID- 25120732 TI - BMP-7 attenuates liver fibrosis via regulation of epidermal growth factor receptor. AB - The aim of this study was to elucidate the effect of bone morphogenetic protein-7 (BMP-7) on liver fibrosis induced by carbon tetrachloride (CCl4) in vivo and on the hepatic stellate cells (HSC) activation in vitro. In vivo, thirty male ICR mice were randomly allocated to three groups, the control group (n = 6), the CCl4 group (n = 18) and the BMP-7+CCl4 group (n = 6). The model of liver fibrosis was induced by intraperitoneal injection with CCl4 three times per week lasting for 12 weeks in CCl4 group and the BMP-7+CCl4 group. After 8 weeks injection with CCl4, mice were intraperitoneal injected with human recombinant BMP-7 in BMP 7+CCl4 group. Meanwhile, mice in the CCl4 group were only intraperitoneal injection with equal amount of saline. The degree of liver fibrosis was assessed by HE and Masson's staining. PCR and western blot were used to detect mRNA and protein levels. In BMP-7+CCl4 group, serum levels of alanine aminotransferase (ALT) and aminotransferase (AST) were decreased and serum albumin (Alb) was increased. Meanwhile, the expressions of transforming growth factor-beta1 (TGF beta1) and alpha-smooth muscle actin (alpha-SMA) were down-regulated by BMP-7 intervention as compared to the CCl4 group (P < 0.05). Furthermore, BMP-7 also suppressed the expression of epidermal growth factor receptor (EGFR) and phosphorylated-epidermal growth factor receptor (pEGFR). HE and Masson stain showed that liver damage was alleviated in BMP-7+CCl4 group. In vitro study, expression of EGFR, TGF-beta1 and alpha-SMA were down regulated by BMP-7 dose dependently, indicating it might effect on suppression of HSC activation. Therefore, our data indicate BMP-7 was capable of inhibiting liver fibrosis and suppressing HSCs activation, and these effects might rely on its crosstalk with EGFR and TGF-beta1. We suggest that BMP-7 may be a potential reagentfor the prevention and treatment of liver fibrosis. PMID- 25120731 TI - Omega-conotoxin MVIIC attenuates neuronal apoptosis in vitro and improves significant recovery after spinal cord injury in vivo in rats. AB - Excessive accumulation of intracellular calcium is the most critical step after spinal cord injury (SCI). Reducing the calcium influx should result in a better recovery from SCI. Calcium channel blockers have been shown a great potential in reducing brain and spinal cord injury. In this study, we first tested the neuroprotective effect of MVIIC on slices of spinal cord subjected to ischemia evaluating cell death and caspase-3 activation. Thereafter, we evaluated the efficacy of MVIIC in ameliorating damage following SCI in rats, for the first time in vivo. The spinal cord slices subjected a pretreatment with MVIIC showed a cell protection with a reduction of dead cells in 24.34% and of caspase-3 specific protease activation. In the in vivo experiment, Wistar rats were subjected to extradural compression of the spinal cord at the T12 vertebral level using a weigh of 70 g/cm, following intralesional treatment with either placebo or MVIIC in different doses (15, 30 and 60 pmol) five minutes after injury. Behavioral testing of hindlimb function was done using the Basso Beattie Bresnahan locomotor rating scale, and revealed significant recovery with 15 pmol (G15) compared to other trauma groups. Also, histological bladder structural revealed significant outcome in G15, with no morphological alterations, and anti NeuN and TUNEL staining showed that G15 provided neuron preservation and indicated that this group had fewer neuron cell death, similar to sham. These results showed the neuroprotective effects of MVIIC in in vitro and in vivo model of SCI with neuronal integrity, bladder and behavioral improvements. PMID- 25120733 TI - Benign notochordal cell tumor: a retrospective study of 11 cases with 13 vertebra bodies. AB - PURPOSE: To analyze the clinical data, MRI, pathological diagnosis, treatment and long-term effects of benign notochordal cell tumor (BNCT), a newly described novel spine tumor. METHODS: We retrospectively studied 11 patients' clinical data of the above. RESULTS: The ratio of males to females was 4:7, and the average age was 49.2 years (range, 18-74 years). Cervical vertebra (5; 38.5%) and thoracic vertebra (5; 38.5%) were the most frequent site followed by the lumbar vertebra (3; 23%). Pain was the main symptom except case 2 who were diagnosed accidently because of prostate cancer. The mean delay from first clinical symptoms to diagnosis was ranged from 2 months to 20 years. MRI showed all BNCTs were osteolytic lesions with hypointense on T1-weighted sequences, hyperintense on T2 weighted sequences. There were 4 vertebral bodies with wedge fracture. There were two cases that had two noncontiguous vertebral bodies with BNCT. In histology, marrow replacement was noted by multivacuolated physaliphorous cells immunoreactive for CK, EMA and S100 protein. All 10 cases except case 2 had vertebral reconstruction and fixation with different methods. Of the 11 patients, 9 had full follow-up data which showed no evidence of recurrence or metastasis without further treatment. CONCLUSION: Noncontiguous multi-centricity BNCTs are rare. No specific vertebrae are more frequently involved. Once BNCT is diagnosed by pathology, the surgical intervention is necessary for the patients with obvious clinical symptoms although it is benign. There is no evidence of BNCT recurrence or metastasis. PMID- 25120734 TI - Primary angiosarcoma of the kidney: case analysis and literature review. AB - OBJECTIVE: To study the clinical presentation, diagnosis, treatment and prognosis of primary angiosarcoma of the kidney. METHODS: We treated a patient with primary angiosarcoma, then searched the published papers with the terms of 'primary angiosarcoma of the kidney' and 'primary renal angiosarcoma' in PubMed database, found 27 patients with detailed data, and analyzed their characters in the clinical presentation, diagnosis, treatment and prognosis. RESULTS: The primary angiosarcoma occurred mainly from 50 years old to 69 years old, predominated in male patients. The clinical presentation was flank pain and hematuria, and the nephrectomy was the mainstay of the treatment; the maximum diameter and the metastasis status at the time of diagnosis had important prognostic value. CONCLUSIONS: The primary angiosarcoma is a rare carcinoma and lacks of specific presentation. Accurate diagnosis depends on pathological examination. Surgery is the mainstay of the treatment, but the prognosis is poor. PMID- 25120735 TI - Immune cells in primary and metastatic gastrointestinal stromal tumors (GIST). AB - We have previously described immune cells in untreated primary gastrointestinal stromal tumors (GIST). Here we compare immune cells in metastatic and primary GIST, and describe their chemoattractants. For this purpose, tissue microarrays from 196 patients, 188 primary and 51 metastasized GIST were constructed for paraffin staining. Quantitative analysis was performed for cells of macrophage lineage (Ki-M1P, CD68), T-cells (CD3, CD56) and B-cells (CD20). Chemokine gene expression was evaluated by real-time RT-PCR. Immuno-localisation was verified by immunofluorescence. Ki-M1P+ cells were the predominant immune cells in both primary and metastatic GIST (2 8.8% +/- 7.1, vs. 26.7% +/- 6.3). CD68+ macrophages were significantly fewer, with no significant difference between primary GIST (3.6% +/- 2.1) and metastases (4.6% +/- 1.5). CD3+ T-cells were the most dominant lymphocytes with a significant increase in metastases (7.3% +/- 2.3 vs. 2.2% +/- 1.8 in primary GIST, P < 0.01). The percentage of CD56+ NK-cells was 1.1% +/- 0.9 in the primary, and 2.4 +/- 0.7 (P < 0.05) in the metastases. The number of CD20+ B-cells was generally low with 0.6% +/- 0.7 in the primary and 1.8% +/- 0.3 (P < 0.05) in the metastases. Analysis of the metastases showed significantly more Ki-M1P+ cells in peritoneal metastases (31.8% +/- 7.4 vs. 18.2% +/- 3.7, P < 0.01), whilst CD3+ T-cells were more common in liver metastases (11.7% +/- 1.8 vs. 4.4% +/- 2.6, P < 0.01). The highest transcript expression was seen for monocyte chemotactic protein 1 (MCP1/CCL2), macrophage inflammatory protein 1alpha (MIP-1alpha/CCL3) and the pro-angiogenic growth related oncoprotein 1 (Gro-alpha/CXCL-1). Whilst the ligands were predominantly expressed in tumor cells, their receptors were mostly present in immune cells. This locally specific microenvironment might influence neoplastic progression of GIST at the different metastatic sites. PMID- 25120736 TI - Angiopoietin-1 gene-modified human mesenchymal stem cells promote angiogenesis and reduce acute pancreatitis in rats. AB - Mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. Angiopoietin-1 (ANGPT1) plays an important role in the regulation of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that ANGPT1 gene-modified MSCs might be a potential therapeutic approach for severe acute pancreatitis (SAP) in rats. Human umbilical cord-derived MSCs with or without transfection with lentiviral vectors containing the ANGPT1 gene were delivered through the tail vein of rats 12 h after induction of SAP. Administration of MSCs alone significantly reduced pancreatic injury and inflammation, as reflected by reductions in pancreatitis severity scores and serum amylase and lipase levels as well as reducing the serum levels of proinflammatory cytokines (TNF-alpha, IFN-gamma, IL-1beta, and IL-6). Furthermore, administration of ANGPT1-transfected MSCs resulted in not only further reductions in pancreatic injury and serum levels of proinflammatory cytokines, but also promotion of pancreatic angiogenesis. These results suggest that MSCs and ANGPT1 have a synergistic role in the treatment of SAP. ANGPT1 gene modified MSCs may be developed as a potential novel therapy strategy for the treatment of SAP. PMID- 25120737 TI - Mast cell chymase in keloid induces profibrotic response via transforming growth factor-beta1/Smad activation in keloid fibroblasts. AB - This study was to examine whether mast cell chymase exists in human keloids and exerts its profibrotic effect via transforming growth factor-beta1/Smad signaling pathway. The number of mast cells and the expression levels of chymase in keloids and normal skin were examined by immunohistochemistry assays. The mRNA expression and activity changes of chymase in keloids and normal skin were determined by real-time quantitative PCR and radioimmunoassay. After keloid fibroblasts were treated with different concentrations of chymase (0, 15, 30, 60, and 120 ng/mL) for various time periods, the proliferation of keloid fibroblasts, collagen synthesis, mRNA and protein expression of TGF-beta1, and the protein expression of phosphorylated Smad2/3, Smad2/3 and Smad7 were investigated using MTT assay, ELISA and Western blotting. Mast cells and chymase exist in keloid. Gene expression and activity of mast cell chymase in keloid are significantly higher than those in normal skin. Chymase promotes keloid fibroblast proliferation and collagen synthesis by activating TGF-beta1. The activation of Smad protein signaling pathway by chymase is related to the elevated P-Smad protein expression in keloid fibroblasts. Our data demonstrated that mast cell chymase plays an important role in keloid formation through TGF-beta1/Smad signaling pathway. PMID- 25120738 TI - Generation of a chimeric dust mite hypoallergen using DNA shuffling for application in allergen-specific immunotherapy. AB - Specific immunotherapy (SIT) is the only treatment that provides long lasting relief of allergy symptoms. Unfortunately, SIT-based traditional remedies carry the risk of producing local and/or systemic side effects. To improve the safety and efficacy of SIT, it has been proposed that SIT must utilize allergens that are hypoallergenic but hyperimmunogenic. Therefore, we used DNA shuffling to generate mutant genes encoding hypoallergens with potent immunogenicity and screened them for their capacity to modify the allergic response. We tentatively shuffled the major group 1 allergen genes from house dust mite, Dermatophagoides farinae and Dermatophagoides pteronyssinus, and discovered a novel chimeric gene, termed C 1. The gene was expressed in Escherichia coli (E. coli) and the chimeric protein C 1 was purified. An animal model of asthma demonstrated that C 1 not only decreased the production of serum IgE and IgG1, and inhibited the production of IL-4 and IL-5 in the bronchoalveolar lavage fluid (BALF). C 1 also boosted the levels of IgG2a and IFN-gamma, which may demonstrate a rebalance of TH1 and TH2 allergic response. Additionally, flow cytometry showed that the immunogenicity of C 1 was higher than that of ProDer f 1, but was not significantly different from that of ProDer p 1. Our findings suggest that the C 1 is hypoallergenic and yet highly immunogenic, which makes it potentially safe and effective for use in SIT of allergic asthma. PMID- 25120739 TI - Interleukin-1beta induces autophagy by affecting calcium homeostasis and trypsinogen activation in pancreatic acinar cells. AB - The strong up-regulation of inflammatory mediators has been reported to play a key role in acute pancreatitis (AP). Elevated serum levels of interleukin-1beta (IL-1beta) are associated with the development of AP. However, the precise effect and mechanism of IL-1beta in AP remains obscure. In this study, we investigated the potential role and mechanism of IL-1beta in AP. We measured autophagy activation in response to IL-1beta in AR42J cells. The disrupting effects of IL 1beta on cellular Ca(2+) were observed. To determine whether the disruption of Ca(2+) signaling has protective effects in vivo during AP, male C57BL/6 mice were treated with cerulein to induce AP. We found that the treatment of AR42J cells with IL-1beta triggered autophagy and that the autophagic flux was impaired. In addition, IL-1beta induced Ca(2+) release from the ER. Furthermore, the expression of the ER stress markers GRP78 and IRE1 also increased. 2APB, an antagonist of the InsP3 receptor, inhibited increased expression of autophagy markers. Subsequent biochemical assays revealed that co-culture with IL-1beta could induce the activation of trypsinogen to trypsin and reduce the viability of acinar cells. Pathological changes of the pancreas were also observed in vivo. We found that the pathological injuries of the pancreas were significantly alleviated in mice co-treated with 2APB. Taken together, our results indicate that IL-1beta can induce trypsin activation and decrease cellular viability in pancreatic acinar cells. These effects depend on impaired autophagy via intracellular calcium changes. Ca(2+) signaling may become a promising therapeutic target in the treatment of pancreatitis. PMID- 25120740 TI - Prognostic value of CD44 expression in non-small cell lung cancer: a systematic review. AB - BACKGROUND: CD44 is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has been reported to correlate with poor prognosis of NSCLC in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and prognosis and clinicopathological features in NSCLC. METHODS: Relevant literatures were identified using PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases (up to February 2014). Data from eligible studies were extracted and included into meta-analysis using a random effects model. Studies were pooled. Summary hazard ratios (HR) and clinical parameters were calculated. RESULTS: We performed a final analysis of 1772 patients from 23 evaluable studies for Prognostic Value and 2167 patients from 28 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD44-V6 for overall survival in NSCLC was 1.63 [95% confidence interval (CI): 1.20-2.21] by univariate analysis and 1.29 (95% CI: 0.71-2.37) by multivariate analysis.The pooled HR of overexprssion panCD44 for overall survival in NSCLC was 1.53 (95% CI: 0.58-4.04) by univariate analysis and 3.00 (95% CI: 1.53-5.87) by multivariate analysis. Overexpression of CD44-V6 is associated with tumor differentiation (poor differentiation, OR = 1.66, 95% CI: 1.12-2.45), tumor histological type [squamous cell carcinomas (SCC), OR = 2.6, 95% CI: 1.63-5.02], clinical TMN stage (TMN stage III, OR = 2.22, 95% CI: 1.44-3.43) and lymph node metastasis (N1-3, 3.52, 95% CI: 2.08 5.93) in patients with NSCLC. However, there was no significant association between CD44-V6 and tumor size [T category, OR = 1.42, 95% CI: 0.73-2.78]. CONCLUSION: Our meta-analysis showed that CD44-V6 is an efficient prognostic factor for NSCLC. Overexpression of CD44-V6 was significantly associated with tumor differentiation, tumor histological type, clinical TMN stage and lymph node metastasis. However, there was no significant association between CD44-V6 and tumor size. Large prospective studies are now needed to confirm the clinical utility of CD44 as an independent prognostic marker. PMID- 25120741 TI - Efficacy of glucocorticoids in rodents of severe acute pancreatitis: a meta analysis. AB - BACKGROUND: The use of corticosteroid in the management of severe acute pancreatitis (SAP) remains contentious and is still being debated despite many pre-clinical studies demonstrating benefits. The limitations of clinical research on corticosteroid in SAP are disparities with regard to benefit, a lack of adequate safety data and insufficient understanding of its mechanisms of action. Thus, we performed a meta-analysis to assess the effectiveness of corticosteroid in experimental SAP and take a closer look at the relation between the animal studies and prospective trials. METHODS: Studies investigating corticosteroid use in rodent animal models of SAP were identified by searching multiple three electronic databases through October 2013, and by reviewing references lists of obtained articles. Data on mortality, changes of ascitic fluid and histopathology of pancreas were extracted. A random-effects model was used to compute the pooled efficacy. Publication bias and sensitivity analysis were also performed. RESULTS: We identified 15 published papers which met our inclusion criteria. Corticosteroid prolonged survival by a factor of 0.35 (95% CI 0.21-0.59). Prophylactic use of corticosteroid showed efficacy with regards to ascitic fluid and histopathology of pancreas, whereas therapeutic use did not. Efficacy was higher in large dose and dexamethasone groups. Study characteristics, namely type of steroids, rout of delivery, genders and strains of animal, accounted for a significant proportion of between-study heterogeneity. No significant publication bias was observed. CONCLUSIONS: On the whole, corticosteroids have showed beneficial effects in rodent animal models of SAP. Prophylactic use of corticosteroid has failed to validate usefulness in prophylaxis of postendoscopic retrogradcholangiopancreatography pancreatitis. Further appropriate and informative animal experiments should be performed before conducting clinical trials investigating therapeutic use in SAP. PMID- 25120742 TI - In vitro differentiation of bone marrow mesenchymal stem cells into endometrial epithelial cells in mouse: a proteomic analysis. AB - OBJECTIVE: Mouse bone marrow mesenchymal stem cells (BMSCs) have been demonstrated to differentiate into female endometrial epithelial cells (EECs) in vivo. Our previous studies demonstrated that BMSCs can differentiate in the direction of EECs when co-cultured with endometrial stromal cells in vitro. Here, we obtain and analyse differential proteins and their relevant pathways in the process of BMSCs differentiating into EECs by isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis. METHODS: A 0.4-MUm pore size indirect co-culture system was established with female mice endometrial stromal cells (EStCs) restricted in the upper Transwell chamber and BMSCs in the lower well plate. After indirect co-culture for several days, the BMSCs were revealed to progressively differentiate towards EECs in vitro. Then, four groups were divided according to different co-culture days with single culture groups of BMSCs as controls. Proteins were detected using iTRAQ based on 2DLC-ESI-MS/MS and data were analysed by bioinformatics. RESULTS: A total number of 311 proteins were detected, of which 210 proteins were identified with relative quantitation. Among them, 107 proteins were differentially expressed with a 1.2-fold change as the benchmark, with 61 up-regulated and 46 down-regulated proteins. Differential proteins CK19 and CK8 were epithelial markers and upregulated. Stromal marker vimentin were downregulated. Top canonical pathways was "remodeling of epithelial adhesions junctions" and "actin cytoskeleton signaling". Top networks was "cell to-cell signaling and interaction, tissue development and cellular movement" regulated by ERK/MAPK and alpha-catenin. CONCLUSION: To the best of our knowledge, this is the first preliminary study of differential protein expression in the differentiation process of BMSCs into EECs in vitro. We further elucidated BMSCs differentiated in the direction of EECs. In addition, ERK/MAPK and alpha catenin played important roles by regulating core differential proteins in the "cell-to-cell signaling and interaction, tissue development and cellular movement" network. PMID- 25120743 TI - Recurrent inflammatory myofibroblastic tumors harboring PIK3CA and KIT mutations. AB - Inflammatory myofibroblastic tumour (IMT) is a relatively rare soft tissue malignancy. It exhibits locally aggressive behavior with a tendency for local recurrence and rare metastasis, and rare recurrent IMTs may show histological progression. The genetic hallmark of IMT is ALK rearrangement from chromosome arm 2p, but gene mutations involved in IMT remain poorly understood. The aim of the present study was to perform a pairwise comparison of the gene mutations occurring in primary and recurrent IMT from the same patient. We conducted a high throughput analysis of 238 known mutations of 19 oncogenes in pairwise comparison primary and recurrent samples from 2 patients of IMT using Sequenom MassARRAY technology. Our results revealed 2 mutations in 2 recurrent lesion samples, including one in exon 11 of the KIT gene, resulting in a T-C substitution at position 1727 (L576P), the recurrent sample underwent histologic progression with "pleomorphic undifferentiated sarcoma-like" transformation; the other mutation was in exon 19 of the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene, resulting in a G-A substitution at position 1624 (E542K). Moreover, no any mutation was found in the primary lesion samples from 2 patients. Our findings suggest that variable genome changes might be present in IMT, especially during the progression from a primary tumour to recurrence. To the best of our knowledge, no such longitudinal study of IMT has been undertaken previously. PMID- 25120744 TI - Accuracy of fine needle aspiration biopsy processed by cytologic smear and cell block techniques for the diagnosis of lacrimal gland tumors: a study of 48 cases. AB - OBJECTIVE: To study the accuracy of fine needle aspiration biopsy (FNAB) processed by smear cytology and cell block (CB) techniques for the diagnosis of lacrimal gland tumors (LGTs). STUDY DESIGN: In a prospective study, we enrolled 48 consecutive patients with LGTs. Immediately after excision of LGTs, the tissues were underwent FNAB with 23-gauge needles. The FNAB samples were processed to produce cytologic smears and CB from which slides were cut for immunohistochemical staining. The remainders were submitted for routine histopathologic processing. The diagnostic value of FNAB was assessed by comparing the FNAB diagnoses to those made by routine histopathology. RESULTS: Cytopathologic evaluations based on smear cytology and CB with sections stained immunohistochemically can distinguish non-epithelial lesions from epithelial ones in all cases. The diagnostic sensitivities, specificities, and accuracies for distinguishing benign from malignant lesions were: cytologic smears--76%, 68%, and 71%, respectively; CB with immunohistochemical staining--88%, 87%, and 88%, respectively. The accuracy of the tissue diagnosis compared to routine histopathology was less for cytologic smears (58%) than for CB with immunohistochemistry (81%; P < 0.05). CONCLUSIONS: FNAB of LGT processed using a CB technique capable of producing immunohistochemically stained slides results in a greater percentage of accurate tissue diagnoses than do cytologic smears, when compared to routine histopathology. PMID- 25120745 TI - IL-22 promotes the migration and invasion of gastric cancer cells via IL 22R1/AKT/MMP-9 signaling. AB - IL-22, one important inflammatory cytokine of the IL-10 family, exerts its functions via IL-22 receptor that is composed of IL-22R1 and IL-10R2 subunits. Although IL-22 expression is reported to be elevated in many cancers, and increased IL-22 expression correlates with tumor progression and poor prognosis, little is known about the role of IL-22 in gastric cancer. In our study, we found that IL-22 stimulation promoted the migration and invasion of SGC-7901 cells. Furthermore, IL-22 increased AKT activation and MMP-9 production in a time- and dose-dependent manner, while knockdown of IL-22R1 attenuated the effect of IL-22 on gastric cancer cells. In addition, blocking of AKT activation suppressed the expression and secretion of MMP-9. Taken together, this present study suggests that IL-22 stimulation enhances the migration and invasion of gastric cancer cells by regulating IL-22R1/AKT/MMP-9 signaling axis. PMID- 25120746 TI - Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma. AB - Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerides into free fatty acids and glycerol. It has recently been found to be involved in cancer progression through the free fatty acid or endocannabinoid network after studies on its function in the endocannabinoid system. Here, we determined a role for MAGL in nasopharyngeal carcinoma (NPC), which is known for its high metastatic potential. Among the different NPC cells we tested, MAGL was highly expressed in high metastatic NPC cells, whereas low metastatic potential NPC cells exhibited lower expression of MAGL. Overexpression of MAGL in low metastatic NPC cells enhanced their motile behavior and metastatic capacity in vivo. Conversely, knockdown of MAGL reduced the motility of highly metastatic cells, reducing their metastatic capacity in vivo. Growth rate was not influenced by MAGL in either high or low metastatic cells. MAGL expression was associated with the epithelial-mesenchymal transition (EMT) proteins, such as E cadherin, vimentin and Snail. It was also related to the sidepopulation (SP) of NPC cells. Our findings establish that MAGL promotes metastases in NPC through EMT, and it may serve as a target for the prevention of NPC metastases. PMID- 25120747 TI - Transplanted bone marrow mesenchymal stem cells protects myocardium by regulating 14-3-3 protein in a rat model of diabetic cardiomyopathy. AB - OBJECTIVE: This study examined the mechanism of bone marrow mesenchymal stem cells (BMSCs) up-regulating the expression of 14-3-3 protein, blocking the myocardial apoptosis in diabetic cardiomyopathy and thereby improving cardiac function. METHODS AND RESULTS: (1) Rat model of diabetic cardiomyopathy was made by feeding rats with high fat/high sugar diet and intraperitoneal injection of small dose of streptozocin (STZ). The model was successfully established as confirmed by the detection of blood sugar, lipid profile, ultrasonographic and hemodynamic examinations. (2) Bone marrow (BM) liquid was taken from the rat femur and tibia bones. The BMSCs were obtained by culture and were confirmed by phase-contrast microscopy and flow cytometry. The BMSCs were transplanted into the rats and fluorescent microscopy showed that transplantation was successful. (3) TUNNEL, Western blotting revealed that in rats of DCM group, myocardial apoptosis was more severe and expression of capase-3 was significantly up regulated while in rats receiving transplantation of BMSCs showed opposite changes, with the differences being statistically significant (P < 0.05). (4) Western blotting exhibited that, compared with DCM group, 14-3-3 and p-Ask1 protein was significantly increased while Ask1 was obviously decreased. CONCLUSION: Our findings suggested that transplantation of bone marrow mesenchymal stem cells could inhibit the myocardial apoptosis in diabetic cardiomyopathy, possibly by up-regulating the expression of 14-3-3 protein and inhibiting the phosphorylation of Ask1. PMID- 25120748 TI - Co-expression of delta-catenin and RhoA is significantly associated with a malignant lung cancer phenotype. AB - Delta-catenin, a member of the p120-catenin subfamily, and the Rho GTPase RhoA both have roles in the regulation of the cytoskeleton. In this study, we found that delta-catenin positive expression and RhoA over-expression is consistently found in non-small cell lung cancer, but not in normal lung tissue, and that their co-expression was significantly associated with histological type, differentiation, pTNM stage, lymphatic metastasis and a poor prognosis. We also demonstrate that delta-catenin can directly interact with RhoA and regulate its activity, which in turn mediates tumor invasion and metastasis. PMID- 25120749 TI - Capsular tension ring implantation after lens extraction for management of subluxated cataracts. AB - PURPOSE: To evaluate the safety and efficacy of implantation of a capsular tension ring (CTR) and posterior chamber intraocular lens (PCIOL) after lens extraction in subluxated cataracts. SETTING: Department of Ophthalmology,General Hospital of PLA, Beijing, China. DESIGN: Prospective case series. METHODS: We selected 36 eyes in 34 patients with zonular dialysis <150 degrees . After emulsification and removal of the residual cortex, we inserted a CTR into the capsular bag to center the PCIOL. We measured preoperative and postoperative best corrected visual acuity (BCVA), centration of the CTR and IOL, and perioperative complications. RESULTS: No capsule collapseor fluctuationof the anterior chamber occurred. Most eyes (63.89%) had nuclear sclerosis of >= 3+. A CTR was implanted into the capsular bag without extension of zonular dialysis. A traumatic subluxated cataract was the most common cause (20 of 36 [55.56%]). We found a subluxated cataract in 3 eyes (3 of 36 [8.33%]) with previous acute angle-closure glaucoma. Mean follow up was 20.3 +/- 2.4 months. Preoperatively, only 5 eyes (13.89%) had a BCVA of >= 20/40, compared with 30eyes at the last visit (83.33%, P<.001). Improved BCVA was achieved in 33 eyes (91.7%) in week 1, and visual acuity remained stable up to 1 year. The CTRs with PCIOL were well centered at 1 year. CONCLUSION: In patients with a subluxated hard cataract <120 degrees , CTR implantation should be performed after lens extraction without extension of zonular dialysis and capsular destabilization. Maintaining anterior chamber depth and avoiding capsular bag collapse are critical. PMID- 25120750 TI - Clinical value of CD133 and nestin in patients with glioma: a population-based study. AB - Cancer stem cell-related (CSC) markers have been suggested to have promising potentials as novel types of prognostic and predictive markers in gliomas. However no single CSC-related marker is currently used in clinical decisions. The aim of this study was to investigate the prognostic value of CD133 and nestin separately and in combination using a novel quantitative approach in a well characterized population-based cohort of glioma patients. The expression of CD133 and nestin was measured by systematic random sampling in stained paraffin sections from 239 glioma patients diagnosed between 2005 and 2009. We found that the expression of CD133 did not correlate with WHO grade, and there was no association with overall survival (OS). The level of nestin correlated positively with WHO grade. In patients with WHO grade II tumors, a high level of nestin was associated with short progression-free survival (PFS) in multivariate analysis. High levels of co-localization were associated with poor PFS in patients with WHO grade II tumors, but not with OS. We conclude that CD133 was not an independent prognostic factor, but a high level of nestin was associated with poor PFS in patients with WHO grade II tumors. The combination of double-immunofluorescence and automated analysis seems to be a feasible and reproducible approach for investigation of the prognostic potential of biomarkers. PMID- 25120751 TI - Expression of leucine aminopeptidase 3 (LAP3) correlates with prognosis and malignant development of human hepatocellular carcinoma (HCC). AB - Leucine aminopeptidases (LAPs) were associated with tumor cell proliferation, invasion and/or angiogenesis. LAP3 is one important member of this family. However, its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. In the present study, we demonstrated that LAP3 expression was significantly up-regulated in HCC tissues as well as cells and was closely correlated with lower differentiation, positive lymph node metastasis and high Ki-67 expression, indicating a poor prognosis. Then cell viability assays, flow cytometry assays, wound-healing assays and matrigel invasion assays were performed to demonstrate that LAP3 promoted HCC cells proliferation by regulating G1/S checkpoint in cell cycle and advanced HCC cells migration. Furthermore, we discovered that knockdown LAP3 will enhance the sensitivity of HCC cells to cisplatin, thus promoting the cell death of HCC cells. Collectively, our results indicated that up-regulated expression of LAP3 might contribute to the proliferation and metastasis of HCC. Our data gains greater insight into the cancer-promoting role of LAP3 and its functions in HCC cells, possibly providing potential therapeutic strategies for clinical trials. PMID- 25120753 TI - Co-expression of uPAR and CXCR4 promotes tumor growth and metastasis in small cell lung cancer. AB - Urokinase-type plasminogen activator receptor (uPAR) and C-X-C-chemokine receptor 4 (CXCR4) are considered as key molecules in invasion and metastasis of several cancers via extracellular matrix degeneration and assist tumor metastasis to specific sites by chemotaxis. However, the combined effect of uPAR and CXCR4 on small cell lung cancer (SCLC), the most aggressive type of lung cancer, is not clear. In this study, we detected the expression of uPAR and CXCR4 in SCLC tissue samples (n = 50) by immunohistochemistry. The tumors with high expression of both uPAR and CXCR4 (12/50) had larger size, higher lymph node (LN) metastasis and worse prognosis of patients than those with low expression of uPAR and CXCR4 (38/50) (P < 0.05). We further identified and isolated the both uPAR and CXCR4 positive expression subpopulation cells (uPAR(+)CXCR4(+) cells) from the SCLC cell line H446 by flow cytometry. The uPAR(+)CXCR4(+) cancer cells showed a higher invasive and migrating capacity in the transwell and wound healing assays compared with other subpopulation cells (P < 0.05). uPAR(+)CXCR4(+) cells injected subcutaneously in nude mice markedly increased tumor growth and induced lung metastasis, while other subpopulation cells did not. In conclusion, these data suggest that uPAR and CXCR4 co-expression predicts worse prognosis of SCLC patients. uPAR(+)CXCR4(+) cells promote the tumor growth and play a potential role in metastasis of SCLC. PMID- 25120754 TI - Effects of simulated microgravity by RCCS on the biological features of Candida albicans. AB - During the spaceflight, a wide variety of microorganisms may be carried to the outer space by astronauts and aviation component. The yeast Candida albicans is an important opportunistic pathogen responsible for a variety of cutaneous and systemic human infections in human body, and the yeast cell itself could be affected by various stressful environmental factors including the weightless environment. We evaluated the effects of simulated microgravity on biological features of Candida albicans using the rotary cell culture system (RCCS). The growth curves of Candida albicans cultured in RCCS were recorded by spectrophotometer, the morphogenic switches were observed by optical microscope, and the viability of cells exposed to the various concentrations of fluconazole solution was assayed by flow cytometry at 7th, 14th and 21st day of experiment. The results showed that Candida albicans SC5314 under modeled microgravity were manifested as the growth curves leftward-shifted, lag phase shortened, along with logarithmic phase and stationary phase forwarded (P < 0.05). The simulated microgravity increased the growth rate and mycelia formation of Candida albicans. A statistically significant decrease in viability was detected in cells cultured for 7 d, 14 d and 21 d in group of simulated microgravity compared with the control group (P < 0.05). The increase of exposure time to simulate microgravity resulted in the decrease of viability of cells accordingly in same drug concentration compared with the control group. The study demonstrated that the three weeks' simulated microgravity in RCCS had a noticeable affect on the growth status of mycelia and spores and the morphogenic switches of Candida albicans, meanwhile, the yeast cells under simulated microgravity showed an increased antifungal susceptibility to fluconazole. PMID- 25120752 TI - RNA-seq identifies determinants of oxaliplatin sensitivity in colorectal cancer cell lines. AB - Oxaliplatin-based chemotherapy, such as FOLFOX, is the first-line therapy for advanced colorectal cancer (CRC) or metastatic CRC patients. However, the partial response of patients to these regimes and the severe peripheral neuropathy toxicity induced by oxaliplatin makes it urgent to figure out biomarkers for oxaliplatin sensitivity to select suitable patients who benefit from these treatments. In present work, 21 CRC cell lines with different sensitivities to oxaliplatin were applied to RNA-seq. The basal expression profiles of these cell lines were correlated to their response to oxaliplatin. Bioinformatics analysis suggested that expression of 58 genes was correlated, negatively or positively, to oxaliplatin response across the 21 CRC cell lines. These 58 genes were mainly enriched in small molecules biochemistry, Wnt/beta-catenin signaling and EMT pathways. The latter two pathways were predicted to be activated in oxaliplatin resistant CRC cell lines. Moreover, 15 genes were validated by qPCR that their expression levels were actually closely correlated to their response to oxaliplatin, in line with the biocomputation prediction. Taken together, our work might provide potential biomarkers for oxaliplatin sensitivity in CRC cell lines and therapeutic targets for combinational therapy with oxaliplatin. PMID- 25120755 TI - Aldo-keto reductase family 1 member B8 is secreted via non-classical pathway. AB - Mouse aldo-keto reductase family 1 member B8 (AKR1B8) has the highest similarity to human aldo-keto reductase family 1 member B10 (AKR1B10), a secretory protein through lysosomes-mediated non-classical secretory pathway. To identify whether AKR1B8 is secreted through the same pathway, we carried out this study. Self developed sandwich ELISA and western blot were used to detect AKR1B8 in cells and culture medium of CT-26 murine colon carcinoma cells. AKR1B8 releases in an independent manner to Brefeldin A, an inhibitor of ER-to-Golgi classical secretion pathway. Several factors, which are involved in the non-classical secretion pathway, such as temperature, ATP and calcium ion, regulated AKR1B8 secretion from mouse colorectal cancer cells CT-26. Lysosomotropic NH4Cl increased AKR1B8 secretion, and AKR1B8 was located in isolated lysosomes. Therefore, AKR1B8 is a new secretory protein through the lysosomes-mediated non classical pathway. PMID- 25120756 TI - Evaluation of glycophenotype in prostatic neoplasm by chemiluminescent assay. AB - This work aimed to evaluate the glycophenotype in normal prostate, bening prostatic hyperplasia (BPH) and prostatic adenocarcinoma (PCa) tissues by a chemiluminescent method. Concanavalin A (Con A), Ulex europaeus agglutinin (UEA I) and Peanut agglutinin (PNA) lectins were conjugated to acridinium ester (lectins-AE). These conjugates remained capable to recognize their specific carbohydrates. Tissue samples were incubated with lectins-AE. The chemiluminescence of the tissue-lectin-AE complex was expressed in relative light units (RLU). Transformed tissues (0.25 cm(2) by 8 um of thickness) showed statistical significant lower alpha-D-glucose/mannose (BPH: 226,931 +/- 17,436; PCa: 239,520 +/- 12,398) and Gal-beta(1-3)-GalNAc (BPH: 28,754 +/- 2,157; PCa: 16,728 +/- 1,204) expression than normal tissues (367,566 +/- 48,550 and 409,289 +/- 22,336, respectively). However, higher alpha-L-fucose expression was observed in PCa (251,118 +/- 14,193) in relation to normal (200,979 +/- 21,318) and BHP (169,758 +/- 10,264) tissues. It was observed an expressive decreasing of the values of RLU by inhibition of the interaction between tissues and lectins-AE using their specific carbohydrates. The relationship between RLU and tissue area showed a linear correlation for all lectin-AE in both transformed tissues. These results indicated that the used method is an efficient tool for specific, sensitive and quantitative analyses of prostatic glycophenotype. PMID- 25120757 TI - Propranolol enhanced adipogenesis instead of induction of apoptosis of hemangiomas stem cells. AB - Propranolol has been widely used in treating infantile hemangiomas (IHs). But recurrence of IHs was found in some cases on cessation of propranolol treatment. The other is that Chinese individuals reacted to propranolol differently from American Whites. Whether the difference of sensitivity is due to the beta adrenoceptor (beta-AR) expression pattern of hemangioma initiating cells remains unclear. In the present study, we isolated hemangioma-derived stem cells (hemSCs) from proliferative IHs and analyzed the biological characteristics and beta-AR expression pattern of hemSCs by immunostaining, Western blotting and multilineage differentiation assay as well. We also tested the effects of propranolol on hemSCs by evaluating VEGF expression, proliferation and apoptosis related parameters. Our results indicated that CD133(+) hemSCs located pre-vascular in proiferative IH tissues. Both beta1 and beta2-AR were expressed, while beta2-AR was dominant on hemSCs. Propranolol at 100-150 MUM inhibited proliferation of hemSCs, not did 50 MUM. Propranolol down-regulated VEGF expression of hemSCs, instead of inducing apoptosis. The adipogenic potential was enhanced by propranolol. Therefore, our current results suggested propranolol could not induce apoptosis of hemSCs, but played a curative role though suppressing VEGF synthesis and enhancement of adipogenesis of hemSCs. Our results might partially provide the insight of mechanism of relapse in some cases on cessation of propranolol treatment. PMID- 25120758 TI - S100B ranks as a new marker of multiple traumas in patients and may accelerate its development by regulating endothelial cell dysfunction. AB - S100 calcium binding protein B (S100B) is recently known as the markers for inflammatory diseases. However, its roles and underlying mechanism on multiple traumas remain unclearly. In this study, total 123 patients (87 male and 36 female) were enrolled and divided into two group: Injury severity score (ISS) >= 16 (n = 69); ISS < 16 (n = 54). ELISA assay confirmed that the circulating S100B levels in multi-trauma were obviously higher than that in healthy volunteers. Additionally, S100B concentrations was associated with injury severity as an obviously higher levels of S100B (2.18 MUg/L) in severe trauma group (ISS >= 16) than 1.26 MUg/L in moderate trauma group (ISS < 16). Furthermore, the average concentration of S100B was 2.91 MUg/L (n = 14) in fatal patients and 2.21 MUg/L in survivors, suggesting an obvious correlation between S100B and the severity degree of multi-injury. Further analysis confirmed an obvious correlation between S100B levels and sE-selectin, and Von willebrand factor (vWF), both of these are the marker of endothelial cell injury. After transfection with pcDNA3.1-S100B, human umbilical vein endothelial cells (HUVECs) cell apoptotic ratio was dramatically up-regulated, concomitant with the increase in IL-6 and IL-8 levels, suggesting that S100B might regulate the development of polytrauma by mediating endothelial cell dysfunction. Together, these results suggest a potential predictive value of S100B and its underlying mechanism in the pathological process of polytrauma. Therefore, this study will support the potential clinical aspect for the diagnostic and treatment of polytrauma and its complications. PMID- 25120759 TI - PNMA1 promotes cell growth in human pancreatic ductal adenocarcinoma. AB - Paraneoplastic Ma1 (PNMA1) is a member of an expanding family of 'brain/testis' proteins involved in an autoimmune disorder defined as paraneoplastic neurological syndrome (PNS). Although it is widely studied in PNS, little is known about the underlying clinical significance and biological function of PNMA1 in tumors. Here, we find that elevated PNMA1 expression is more commonly observed in pancreatic ductal adenocarcinoma (PDAC) cell lines, compared with normal pancreatic cell and tissues from pancreatic ductal adenocarcinoma patient. Besides, higher PNMA1 expression is closely correlated with large tumor size. Suppression of endogenous PNMA1 expression decreases cell viability and promotes cell apoptosis. Subsequent studies reveal that the PI3K/AKT, MAPK/ERK pathway and members of the anti-apoptotic Bcl-2 family may be involved in the pro-survival and anti-apoptotic effect of PNMA1 on PDAC. Taken together, this study provides evidence that PNMA1 is involved in tumor growth of pancreatic carcinoma and PNMA1 related pathways might represent a new treatment strategy. PMID- 25120761 TI - RNAi-mediated silencing of the Skp-2 gene causes inhibition of growth and induction of apoptosis in human renal carcinoma cells. AB - Renal cancer ranks one of the most frequent causes of cancer death in the world. S-phase kinase-associated protein 2 (SKP 2) is overexpressed in human tumors and has prognostic value in many cancers including renal cancer, indicating its potential as a therapeutic target. In this study, we investigated the therapeutic potential of Skp-2 in renal cancer using the technique of RNA silencing via short hairpin RNA (shRNA). Synthetic shRNA duplexes against Skp-2 were introduced to down-regulate the expression of Skp-2 in a highly malignant renal carcinoma cell line, ACHN. The results indicated that siRNA targeting of Skp-2 could lead to an efficient and specific inhibition of endogenous Skp-2 activity. Furthermore, we found that depletion of Skp-2 caused a dramatic cell cycle arrest, followed by massive apoptotic cell death, and eventually resulted in a significant decrease in growth, viability and tumor formation in renal cancer cell lines studied. PMID- 25120760 TI - HMGB1 enhances smooth muscle cell proliferation and migration in pulmonary artery remodeling. AB - HMGB1 is a necessary and critical mediator of acute lung injury and can act as a chemoattractant and anti-apoptosis factor in injury or repair in diseases. In this study we sought to determine whether HMGB1 is involved in the remodeling of pulmonary artery and investigate the mechanism. A rat model of pulmonary artery remodeling was successful induced with LPS infusion and the increasing of pulmonary arteries media was obviously inhibited in rats treated with thrice inject of HMGB1 neutralizing antibody. The percent of areas of tunica media to total artery wall was (0.53 +/- 0.15), (0.81 +/- 0.10) and (0.59 +/- 0.11) in control, LPS and antibody group respectively (p<0.05). Meanwhile, treatment with HMGB1 neutralizing antibody not only decreased the level of HMGB1 mRNA and protein significantly, but inhibited the expression of PCAN and Bcl-2 as well. On the contrary, Bax, a gen which represented the apoptosis, revealed an absolutely reversed trend to Bcl-2 in pulmonary arteries. Experiments in vitro showed that HMGB1 could stimulate the proliferation of hPASMC in MTT test and increase the number of migrated cells in a concentration-dependent manner in chemotaxis assay using modified Boyden chambers. In conclusion, data from this study support the concept that HMGB1 is involved in the remodeling of pulmonary artery by enhancing proliferation and migration of smooth muscle cell. Inhibiting HMGB1 may be a new target to deal with the remodeling of pulmonary artery. PMID- 25120762 TI - Identification of collaboration patterns of dysfunctional pathways in breast cancer. AB - Breast cancer (BC) is the most common malignancy among women. We aimed to illuminate the molecular dysfunctional mechanisms of BC progression. The mRNA expression profile of BC GSE15852 was downloaded from Gene Expression Omnibus database, including 43 normal samples and 43 cancer samples. Differentially expressed genes (DEGs) in BC were screened using the t-test by Benjamin and Hochberg method. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the selected DEGs were enriched using Hypergeomeric distribution model. In addition, functional similarity network among the enriched pathways was constructed to further analyze the collaboration of these pathways. We found 848 down-regulated DEGs were associated with 16 significant dysfunctional pathways, including PPAR signaling fatty acid metabolism, and 1584 up-regulated DEGs were related to 6 significant dysfunctional pathways, like cell cycle, protein export, and antigen processing and presentation in BC samples. Crosstalk network analysis of pathways indicated that pyruvate metabolism, propanoate metabolism, and glycolysis gluconeogenesis were the pathways with closest connections with other pathways in BC. In addition, other antigen processing and presentation, including 19 DEGs; PPAR signaling pathway, including 18 DEGs; and pyruvate metabolism pathway, including 13 DEGs were further analyzed. Our results suggested that dysfunctional of significant pathways can greatly affect the progression of BC. Several significant disorder pathways were enriched in our comprehensive study. They may provide guidelines to explore the dysfunctional mechanism of BC progression. PMID- 25120763 TI - Unclassified renal cell carcinoma: a clinicopathological, comparative genomic hybridization, and whole-genome exon sequencing study. AB - Unclassified renal cell carcinoma (URCC) is a rare variant of RCC, accounting for only 3-5% of all cases. Studies on the molecular genetics of URCC are limited, and hence, we report on 2 cases of URCC analyzed using comparative genome hybridization (CGH) and the genome-wide human exon GeneChip technique to identify the genomic alterations of URCC. Both URCC patients (mean age, 72 years) presented at an advanced stage and died within 30 months post-surgery. Histologically, the URCCs were composed of undifferentiated, multinucleated, giant cells with eosinophilic cytoplasm. Immunostaining revealed that both URCC cases had strong p53 protein expression and partial expression of cluster of differentiation-10 and cytokeratin. The CGH profiles showed chromosomal imbalances in both URCC cases: gains were observed in chromosomes 1p11-12, 1q12 13, 2q20-23, 3q22-23, 8p12, and 16q11-15, whereas losses were detected on chromosomes 1q22-23, 3p12-22, 5p30-ter, 6p, 11q, 16q18-22, 17p12-14, and 20p. Compared with 18 normal renal tissues, 40 mutated genes were detected in the URCC tissues, including 32 missense and 8 silent mutations. Functional enrichment analysis revealed that the missense mutation genes were involved in 11 different biological processes and pathways, including cell cycle regulation, lipid localization and transport, neuropeptide signaling, organic ether metabolism, and ATP-binding cassette transporter signaling. Our findings indicate that URCC may be a highly aggressive cancer, and the genetic alterations identified herein may provide clues regarding the tumorigenesis of URCC and serve as a basis for the development of targeted therapies against URCC in the future. PMID- 25120764 TI - Monocyte chemotactic protein-1 expression as a prognosic biomarker in patients with solid tumor: a meta analysis. AB - PURPOSE: A great deal of studies have been performed on the prognostic value of monocyte chemotactic protein-1 (MCP-1) in solid tumors in recent years. However, no consistent outcomes are reported. Therefore, the prognostic value of MCP-1 still remains controversial in patients with solid tumors. Here we aimed to evaluate the prognostic value of MCP-1 expression for patients with solid tumors. METHODS: Comprehensive literature was selected from PUBMED and EMBASE and clinical studies which reported analysis of survival data about MCP-1 in solid tumors were included. Stata 11.0 was used for performing a meta-analysis on evaluating the relation between MCP-1 and clinical staging, overall survival (OS) and disease free survival (DFS). RESULTS: Eleven studies with a total of 1324 patients with solid tumors were included into our meta-analysis. The result showed that high concentration of MCP-1 was related to a worse OS (HR = 1.95, 95% CI 1.32-2.88). The subgroup analysis on different location of tumors showed that high concentration of MCP-1 meant bad prognosis in patients with digestive cancer (HR = 2.66, 95% CI 1.44-4.91) and urogenital cancer (HR = 2.23, 95% CI 1.61 3.10), even head and neck cancer (HR = 1.99, 95% CI 0.95-4.18) other than respiratory cancer (HR = 1.10, 95% CI 0.39-3.11). Another subgroup analysed on different sites of cancer and indicated a poor prognosis on adenocarcinoma (HR = 2.10, 95% CI 1.63-2.69). CONCLUSIONS: Our findings suggest that MCP-1 can be regarded as a poor prognostic maker for solid tumors and may represent important new therapeutic targets. PMID- 25120765 TI - Increased HIF-1alpha expression in tumor cells and lymphocytes of tumor microenvironments predicts unfavorable survival in esophageal squamous cell carcinoma patients. AB - The expression of hypoxia-induced factor (HIF)-1alpha is up-regulated in tumor microenvironments under hypoxia condition. However, the prognostic significance of HIF-1alpha in esophageal squamous cell carcinoma (ESCC) is still elusive. We measured the HIF-1alpha expression by immunochemistry in tumor specimens from 136 resected ESCC; in the current study, the HIF-1alpha expression in tumor cells was significantly associated with tumor stage (P = 0.003) and lymph node metastasis (P = 0.006); whereas the HIF-1alpha expression in tumor-infiltrating lymphocytes (TILs) had no relationship with patients' clinicopathological parameters. Patients with high HIF-1alpha expression in tumor cells or in TILs showed worse survival related to those with low HIF-1alpha expression. Multivariate analysis demonstrated that expression of HIF-1alpha in TILs was an independent factor for DFS (P = 0.007) and OS (P = 0.013). Additionally, the expression of HIF-1alpha in tumor cells was an independent factor for DFS (P = 0.037) and OS (P = 0.033) in locoregional ESCC patients, whereas the expression of HIF-1alpha in TILs was an independent factor for DFS (P = 0.048) and OS (P = 0.039) in metastatic ESCC patients. Correlation analysis revealed that expressions of HIF-1alpha in tumor cells and in TILs were positively correlated, and patients with combined high HIF 1alpha in both tumor cells and TILs had the worst survivals (P < 0.05). These findings suggest that the HIF-1alpha expressions in different cell populations of ESCC microenvironments have different clinical relevance and prognostic impact on patients. PMID- 25120766 TI - RNAi screening identifies HAT1 as a potential drug target in esophageal squamous cell carcinoma. AB - Esophageal carcinoma (EC) is one of the most fatal carcinomas of the gastrointestinal tract. Aberrant activity of histone acetyltransferases (HATs)/deacetylases (HDACs) play a critical role in carcinogenesis through the regulation of the genes involved in cell differentiation, proliferation, and apoptosis. However, cellular functions of HATs/HDACs in esophageal cancer and its molecular mechanisms remain unclear. An RNAi screen was used in this study to identify the histone acetyltransferases (HATs) and deacetylases (HDACs) that could be critical for the survival of EC cells. We demonstrated that HAT1 (histone acetyltransferase 1) was an important determinant to regulate the proliferation of human EC Eca-109 cells. Furthermore, we showed that the knockdown of HAT1 induced a G2/M cell cycle arrest, which was associated with the disruption of cell cycle-related events, including the decrease of cyclinD1 as well as alteration in cyclinB1 expression. The expression of HAT1 was validated to be higher in the primary tumors and adjacent tissue as compared to that of the normal esophageal tissue. Furthermore, we found that HAT1 expression was directly correlated with the poor tumor differentiation of EC tissue, which suggested that HAT1 played an important role in esophageal carcinoma and that it could be a novel EC therapeutic target. PMID- 25120767 TI - Nuclear localizaiton of beta-catenin is associated with poor survival and chemo /radioresistance in human cervical squamous cell cancer. AB - Nuclear expression of beta-catenin has been suggested as an independent prognostic marker in a variety of cancers. The objective of this study was to investigate the clinicopathologic significance of nuclear beta-catenin expression in patients with cervical squamous cell carcinoma (CSCC). In this original research article, we detected nuclear beta-catenin expression in 29/171 CSCC tissues (17.0%). Patients without nuclear beta-catenin expression had a significantly better outcome than patients with nuclear beta-catenin expression (93.7% versus 82.7% P = 0.027). Furthermore, nuclear beta-catenin expression was predictive of prognosis in CSCC patients with early stage disease (FIGO stage I or tumor size <= 4 cm), with well/moderately differentiated tumors, or lymph node metastasis. Interestingly, nuclear beta-catenin expression correlated with poor outcome in patients who received postoperative chemotherapy or radiotherapy. Multivariate analysis suggested that nuclear beta-catenin expression is an independent prognostic indicator in CSCC. Our findings suggest that nuclear beta catenin expression may be used as a prognostic biomarker in CSCC, especially for patients with early stage disease, well/moderately differentiated tumors, or lymph node metastasis. Moreover, nuclear beta-catenin expression has potential as a predictive marker of chemoresistance and radioresistance in CSCC. PMID- 25120768 TI - Overexpression of MAGE-D4 in colorectal cancer is a potentially prognostic biomarker and immunotherapy target. AB - Melanoma-associated antigen D4 (MAGE-D4) is a novel member of MAGE family. This study aimed to examine the expression and immunogenicity of MAGE-D4 in colorectal cancer (CRC) to determine its potential as a prognosis and immunotherapeutic target. The expression of MAGE-D4 mRNA and protein was determined by RT-PCR and immunohistochemistry (IHC) in CRCs with paired adjacent non-tumor tissues, colorectal adenomas and normal colorectal tissues, respectively. Sera from 64 CRC patients were tested for MAGE-D4 antibody by ELISA. MAGE-D4 mRNA was more frequently expressed in CRCs (76.7%, 46/60) than in adjacent non-tumor tissues (15.0%, 9/60). MAGE-D4 protein was detected in all the CRC tissues tested, 70.0% of which showed high expression. There was no MAGE-D4 protein detected in any paired adjacent non-tumor tissue. No MAGE-D4 expression was found in colorectal adenomas and normal colorectal tissues by either RT-PCR or immunohistochemistry. Patients with high MAGE-D4 protein expression had significantly shorter overall survival than those with low MAGE-D4 protein expression (median, 68.6 vs 122.2 months; P=0.030). Furthermore, multivariate analysis exhibited high MAGE-D4 protein expression had a trend toward an independent prognostic factor (hazard ratio: 6.124; P=0.050). Humoral immunity to MAGE-D4 was detected in 12 of 64 (18.8%) CRC patients' sera but not in 77 healthy donors. There was no correlation between MAGE-D4 expression, serum antibody and clinicopathological parameters. These findings suggest MAGE-D4 may serve as a potentially prognostic biomarker and an attractive target of immunotherapy in CRC. PMID- 25120769 TI - Expression of aquaporin 8 and phosphorylation of Erk1/2 in cervical epithelial carcinogenesis: correlation with clinicopathological parameters. AB - Overexpression of aquaporins (AQPs) has been reported in several human cancers. Extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQPs expression. In this study, we examined cervical tissue samples to establish the relationship between Erk1/2 and AQPs in cervical carcinoma by RT-PCR, Western blot and immunohistochemistry. We also examined the relationship between AQP8, Erk1/2 and clinicopathological variables in patients with cervical cancer. Our results showed that Erk1/2 was differentially expressed at the level of transcription and was most highly expressed in CIN samples (P < 0.05). At the level of translation, significant differences were seen in the expression of AQP8, Erk1/2 and P-Erk1/2 (P < 0.05). Expression was highest in CIN samples, where 80.9%, 76.6%, and 66% of samples were positive for AQP8, Erk1/2 and P-Erk1/2, respectively. Expression in cervical carcinoma samples was higher than in normal cervical tissues (P < 0.01). AQP8 expression was associated with the depth of invasion of cervical cancer cells, and the expression of Erk1/2 and P-Erk1/2 was increased in earlier clinical stages and in lymphatic metastasis. AQP8 expression was positively correlated with Erk1/2 expression in cervical cancer. In conclusions, increased AQP8, Erk1/2 and P-Erk1/2 expression may play a role in transformation of CIN into cervical cancer, and in early invasion and lymphatic metastasis of cervical cancer. These proteins could potentially be used as molecular markers for early diagnosis of cervical carcinoma. PMID- 25120771 TI - Inhibitory effect of beta-elemene on human breast cancer cells. AB - It has been approved for the clinical application of beta-elemene to treat various cancers mainly brain tumors in China. In the present study, we found that beta-elemene significantly inhibited the in vitro growth of human breast cancer cells by inducing apoptosis. In addition, beta-elemene also induced the conversion of LC3-I into LC3-II as well as the formation of autolysosomes, indicating the activation of autophagy. Interestingly, inhibition of autophagy significantly potentiated the growth-inhibitory effect of beta-elemene on breast cancer cells. In summary, beta-elemene induced cytoprotective autophagy in human breast cancer cells in addition to apoptosis. Inhibition of autophagy significantly enhanced the cytotoxicity of beta-elemene to human breast cancer cells. Therefore, combination of beta-elemene with autophagy inhibitors could be a promising strategy for the treatment of breast cancer. PMID- 25120770 TI - Apigenin suppresses GLUT-1 and p-AKT expression to enhance the chemosensitivity to cisplatin of laryngeal carcinoma Hep-2 cells: an in vitro study. AB - Glucose transporter-1 (GLUT-1) and PI3K/Akt are known to be closely involved in resistance to chemotherapy. Co-targeted therapy reducing GLUT-1 expression and PI3K/Akt pathway activity may overcome the chemoresistance of human cancers. Apigenin may inhibit the expression of GLUT-1 and the PI3K/Akt pathway. We hypothesized that over-expression of GLUT-1 and p-Akt was associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. We explored whether apigenin inhibited GLUT-1 and p-Akt, resulting in sensitization of laryngeal carcinoma Hep-2 cells to cisplatin. Real-time RT-PCR and Western blotting confirmed the presence of GLUT-1 mRNA, and GLUT-1 and p-Akt proteins in Hep-2 cells. We found that resistance or insensitivity of Hep-2 cells to cisplatin might be associated with such expression. Apigenin markedly enhanced the cisplatin-induced suppression of Hep-2 cell growth. This effect was concentration and time-dependent. Thus apigenin may significantly reduce the levels of GLUT-1 mRNA, and GLUT-1 and p-Akt proteins, in cisplatin-treated Hep-2 cells, in a concentration- and time-dependent manner. To conclude, overexpression of GLUT-1 mRNA may be associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. Apigenin may enhance the sensitivity to cisplatin of laryngeal carcinoma cells via inhibition of GLUT-1 and p-Akt expression. PMID- 25120772 TI - Effects of BMSCs interactions with adventitial fibroblasts in transdifferentiation and ultrastructure processes. AB - In this study an in vitro model of simulated blood vessel injury was used to study the effects of bone marrow-derived mesenchymal stem cells (BMSCs) morphology and to detect vascular smooth muscle actin (SM alpha-actin) expression in the presence of adventitial fibroblasts. BMSCs from rats with DAPI-labeled nuclei were co-cultured with adventitial fibroblasts for 7 days, while BMSCs cultured alone served as controls. Cell morphology of BMSCs was assessed by laser confocal microscopy and SM alpha-actin or calponin expression in BMSCs was detected by immunofluorescence staining. The expression of SM alpha-actin mRNA was identified using RT-PCR. Cell ultrastructure was assessed by electron microscopy. The results demonstrate that BMSCs with DAPI-labeled nuclei were smaller compared with fibroblasts, and their nuclei emitted a blue fluorescence. Most BMSCs displayed a polygonal shape changing from their original long fusiform shape. BMSCs with blue nuclei and red cytoplasm (SM alpha-actin positive or calponin positive) were observed, and a substantial number of filaments were present in the cytoplasm as observed under electron microscopy. The number of these cells increased as a function of culture duration. However, SM alpha-actin expression was weak and calponin expression was not detected in the control group. This study provides important new information on the characterization of artherosclerosis pathogenesis and vascular restenosis after blood vessel injury. Our findings demonstrate that direct interactions with adventitial fibroblasts can induce vascular smooth muscle-like cell differentiation in BMSCs. PMID- 25120773 TI - Expression profiles of HA117 and its neighboring gene DPF3 in different colon segments of Hirschsprung's disease. AB - Hirschsprung's disease (HSCR) is characterized by the absence of enteric ganglion cells along variable regions of the colon. Established theory demonstrates that HSCR is the consequence caused by the abnormal arrest of the migration and differentiation of neural crest-derived stem cells (NCSCs). And retinoid signaling was considered to be involved. We speculated that, HA117, a retinoid related transcript of a long noncoding RNA (LncRNA), may be involved in the genesis of HSCR. In current research, colon specimens were collected from 25 HSCR patients and grouped into 3 segments: proximal anastomosis, dilated segment and stenotic segment. Real-Time PCR was used to analyze the expression profiles of HA117 and its neighboring gene DPF3 in different colon segments. Fluorescence in situ hybridization (FISH) was employed to detect the distribution of HA117 in the gut wall. Immunohistochemistry was performed to analyze the protein expression of DPF3 in different colon segments. HA117 expression in stenotic segment was higher compared to proximal anastomosis and dilated segment (p < 0.05). Whereas DPF3b mRNA was lower in stenotic segment than that in two other segments (p < 0.05). FISH detected HA117 was distributed in mucosa and muscle layer, mainly present in stenotic segment. Immunohistochemical staining showed that intensive DPF3 staining occurred in proximal anastomosis and the positive staining was hardly observed in stenotic segment. The results suggested that HA117 may be a factor exerting an anti-differentiation or or anti-maturation role in the genesis of HSCR. This gave us a novel cue for better understanding the etiology of HSCR. PMID- 25120774 TI - Possible prognostic significance of p53, cyclin D1 and Ki-67 in the second primary malignancy of patients with double primary malignancies. AB - Patients with two types of primary cancers are rare. In this study, we investigated the expression of p53, cyclin D1, and Ki-67 in the second primary malignancy. Tissue samples were obtained from the second primary cancer site of 43 patients who met the diagnostic criteria for double primary cancer. p53, cyclin D1 and Ki-67 were determined using immunohistochemistry. Categorical variables were compared using the Chi-squared test; correlation between data scores and histology was calculated using the Spearman's rank-order correlation. The expression rates of p53, cyclin D1 and Ki-67 in the second primary malignancy site were 60.5%, 30.2% and 65.1% respectively. p53 expression showed statistically significant association with tumor occurrence interval, pathological grading and nodal metastasis (p < 0.05). Positive correlation was detected between the expression of cyclin D1 and Ki-67 and the expression of p53 (r = 0.313, p = 0.041; r = 0.319, p = 0.037, respectively). High-expressing p53 or cyclin D second primary malignancies were associated with decreased overall survival (p = 0.040 and p = 0.043, respectively). Ki-67 expression levels did not exhibit statistically significant differences in survival. In conclusion, elevated protein expression of p53, cyclin D1 and Ki-67 in the second primary malignancy is an indicator of more aggressive malignant behavior of the secondary tumor. These markers may have prognostic value in the clinical setting. PMID- 25120775 TI - Knockdown of Aurora-B inhibits osteosarcoma cell invasion and migration via modulating PI3K/Akt/NF-kappaB signaling pathway. AB - Increasing evidences reveal that Aurora-B may be involved in metastasis of malignant tumor. In this study, we investigated the inhibitory effect of Aurora-B on invasion and migration of OS cells and the activity of PI3K/Akt/NF-kappaB signaling pathway in vitro. The expression of Aurora-B and p-Akt (Ser473) proteins was detected by immunohistochemistry in OS tissues from 24 patients with pulmonary metastatic disease, and the relationship between Aurora-B and p-Akt was investigated. The results showed that there was a positive correlation between Aurora-B and p-Akt protein expression. Furthermore, we down-regulated the expression of Aurora-B through a recombinant lentivirus (Lv-shAURKB). Migration and invasion of cells were investigated by wound healing and transwell invasion assays. Results showed that silencing Aurora-B inhibited cell migratory and invasive ability of OS cells in vitro. Finally, knockdown of Aurora-B suppresses the activity of PI3K/Akt/NF-kappaB signaling pathway in OS cells. Our results indicated that knockdown of Aurora-B suppresses OS cells migratory and invasive ability via modulating the "PI3K/Akt/NF-kappaB" signaling pathway in vitro. The Aurora-B blocker may be a new therapeutic strategy in OS management. PMID- 25120776 TI - Increased chromogranin A and neuron-specific enolase in rats with chronic nonbacterial prostatitis induced by 17-beta estradiol combined with castration. AB - Although chronic nonbacterial prostatitis (CNBP) is a common diagnosis in middle aged men, the etiology of this disease remains poorly understood. Neuroendocrine cells play an important role in the neuroendocrine regulation of the prostate, and chromogranin A (CgA) and neuron-specific enolase (NSE) are regarded as classic markers of neuroendocrine cells. This study aimed to determine CgA and NSE levels in a CNBP rat model to evaluate the role of neuroendocrine cells in the pathogenesis of CNBP. For developing a CNBP rat model, we examined the ability of 17-beta estradiol and surgical castration alone or in combination to induce CNBP. Histologic inflammation of the prostate was assessed in CNBP-induced rats by hematoxylin-eosin staining, whereas CgA and NSE protein levels were assessed by immunohistochemistry, Western blot analysis, and enzyme-linked immunosorbent assays. Our results showed that 17-beta estradiol combined with castration successfully induced CNBP and that CgA and NSE levels were increased in the prostate of CNBP rats as compared to those without CNBP. These findings indicate that the neuroendocrine regulation mediated by neuroendocrine cells may be involved in the pathogenesis of CNBP. PMID- 25120777 TI - Granular cell tumor of the esophagus: a clinicopathological study of 31 cases. AB - Granular cell tumors (GCTs) in esophagus are rare tumors lacking of systemic large group reports. In this study, we summarized the clinical characteristics, histological features and therapeutic approaches of 31 cases. GCTs generally located at middle and distal of the esophagus in middle aged and elderly patients with no incidence of gender differences. Histologically, tumor cells were mainly plump and polygonal with abundant, granular, amphophilic or eosinophilic cytoplasm. The growth pattern was solid or nested, usually with minimal infiltration and inflammatory infiltrates and lymphoid aggregation. All GCTs in the present study were benign according to Nasser criteria. Nestin, NSE, CD68 and S100 protein were moderate to strong positive. Moreover, a developmental morphology of a GCT was found, which included areas of relatively normal Schwann cells, transitional cells and typical cells of GCTs. All patients received endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Twenty-six patients were followed up and remained clinically well. In conclusion, GCTs of esophagus are neurogenic origin tumors with favourable prognosis. Definite diagnosis of GCTs relies upon pathological examination. The Nasser criteria for stratification are practical in guiding treatment strategy. ESD is a recommended therapeutic strategy, and the range of application is expanding. PMID- 25120778 TI - Alterations of microRNAs are associated with impaired growth of MCF-7 breast cancer cells induced by inhibition of casein kinase 2. AB - BACKGROUND AND AIM: Protein Kinase (casein kinase 2, CK2) is a pleiotropic serine threonine kinase that is frequently dysregulated in many human tumors; microRNAs (miRNAs) are a class of small noncoding RNAs which play important roles in human cancers. This study aimed to investigate the role of CK2 and miRNA expression in breast cancer. METHODS: Casein kinase 2 in MCF-7 breast cancer cell line was inhibited by the CK2 inhibitor TBB (4,5,6,7-tetrabromobenzotriazole), then cell proliferation was studied using MTT assay, and cell cycle distribution and apoptosis were detected by flow cytometry. The alteration of microRNAs expression profile was determined by microarray technology, followed by RT-PCR confirmation. RESULTS: Here, we for the first time showed that inhibition of CK2 in MCF-7 breast cancer cells causes suppressed cell growth, which was related with dysregulation of the miRNA profile and altered expression. CK2 inhibition induced the up-regulated expression of 17 miRNAs and 10 down-regulated microRNAs which contributed to the impaired growth, inhibited cell cycle progress and increased apoptosis of MCF-7 cells by a CK2 inhibitor. CONCLUSIONS: These findings highlight the potential role of dysregulated miRNA expression regulated by CK2 in breast cancer. PMID- 25120779 TI - Cyclin D1b overexpression inhibits cell proliferation and induces cell apoptosis in cervical cancer cells in vitro and in vivo. AB - Cyclin D1b is one of two proteins translated from cyclin D1 transcripts (isoforms a and b) that are generated due to gene polymorphism. Our previous study has reported low cyclin D1b expression in cervical cancer tissue, with an expression level in moderately or poorly differentiated tissues that was significantly lower than that in well-differentiated tissues. However, the functional role of cyclin D1b in cervical cancer remains to be elucidated. In this study, using a cervical cancer cell line with stable expression of cyclin D1b, we found that upregulation of cyclin D1b initiated cell cycle arrest at the G0/G1 phase and induced apoptosis, thereby inhibiting cell proliferation and colony formation. Furthermore, xenograft transplantation experiments in nude mice demonstrated that cyclin D1b upregulation inhibited cancer growth and induce apoptosis in vivo. In conclusion, the present study indicates anti-tumor effects of cyclin D1b in cervical cancer, suggesting that cyclin D1b may represent a potential therapeutic target for cervical cancer. PMID- 25120780 TI - Different levels of circulating Th22 cell and its related molecules in Graves' disease and Hashimoto's thyroiditis. AB - PURPOSE: The aim of this study was to make a comparative analysis of the possible different expression of Th22 cells in two subtypes of autoimmune thyroid diseases (AITDs), i.e., Graves' disease (GD) and Hashimoto's thyroiditis (HT). METHODS: We recruited 61 AITDs patients (31 GD and 30 HT) and 22 controls. Serum level of IL 22 was measured by enzyme linked immunosorbent assay (ELISA). The proportion of Th22 cells in peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry. The messenger RNA (mRNA) expressions of IL-22, its receptors (IL10R2, IL22R1) and key transcription factor (aryl hydrocarbon receptor, AHR) in PBMCs were assayed by quantitative reverse transcription polymerase chain reaction (qRT PCR). Several cytokines of the cultured PBMCs were also measured under IL-22 stimulation. RESULTS: The proportion of Th22 cells, serum IL22 level and IL-22 mRNA expression were significantly higher in patients with GD than in healthy controls. Additionally, AHR increased in GD patients compared to healthy controls. However, the elevation of Th22 cells and their relative cytokines was not found in patients with HT. Consistent with specific mRNAs expression of cultured PBMCs, IL-4 increment in supernatant was much higher in GD group than in control group, while IFN-gamma levels were decreased under IL-22 stimulation. CONCLUSION: Th22 cells may participate in the pathogenesis of AITDs as a proinflammatory factor, especially in GD, through expressing and secreting IL-22. PMID- 25120781 TI - Vascular alterations in schwannoma. AB - Schwannomas or neurilemmoma are benign peripheral nerve sheath tumors, which most frequently occur at the cerebellopontine angle. This morphologic study examines vascular alterations in these tumors, comparing them to other benign spindle cell neoplasms of the nervous system, while correlating these findings with evidence of vascular permeability. Thirty-four nervous system spindle cell neoplasms, sixteen schwannomas, nine fibroblastic/transitional meningiomas and nine peripheral neurofibromas were stained with H&E, Prussian-blue stain, and immunoreacted for factor VIII-related antigen and interstitial albumin. Schwannomas had focal clusters of vascular proliferation including groups of small thin-walled vessels, as well as larger vessels with extensive hyalinization. Neurofibromas and meningiomas almost uniformly had modest numbers of well-defined, thin walled individual vessels. Free hemosiderin and hemosiderin laden macrophages were frequently identified in schwannomas. Prussian-blue stain for iron revealed focal or fairly widespread positivity in almost all schwannomas, only one meningioma and none of the neurofibromas. Immunoreaction for albumin demonstrated leakage of vascular proteins into the interstitium confirming tumor vessel permeability in schwannomas. Neither neurofibromas nor meningiomas displayed any detectable interstitial albumin. The above findings confirm a degree of reactive proliferation of vessels in schwannoma along with functional deficits in their vascular integrity with permeability to protein and blood. The presence of hyalinized vessels, hemosiderin, both free and within macrophages, and more readily evident Prussian blue staining, may provide an additional diagnostic clue in discriminating between histologically similar spindle cell lesions. The study however raises the possibility that these changes likely precede or facilitate the degenerative 'ancient change' seen in some schwannoma. PMID- 25120782 TI - miR-218 modulate hepatocellular carcinoma cell proliferation through PTEN/AKT/PI3K pathway and HoxA10. AB - PURPOSE: To investigate the regulatory mechanism of miR-218 in human hepatocellular carcinoma (HCC). METHODS: qPCR was used to compare the expression levels miR-218 among six hepatocellular carcinoma cell lines and normal liver tissues. After transfecting MHCC97L cells with either miR-218 mimics or miR-218 inhibitor, western blotting was used to examine the expressing patterns of cyclinD1, p21, and PTEN/AKT/PI3K signaling pathway-related proteins. MTT and colony forming assay was used to assess the capability of cell proliferation. Bioinformatic method was applied to predict the binding of miR-218 on HoxA10, and western blotting was used to examine the modulatory effect of miR-218 AND HoxA10 on PTEN/AKT/PI3K pathway in HCC. RESULTS: The expression levels of miR-218 were frequently lower in HCC cell lines than in normal liver tissues. Over-expression of miR-218 in HCC cells significantly decreased cell proliferation whereas inhibiting miR-218 promoted cancer cell proliferation. Western blotting analysis demonstrated that tumorigenesis related protein cyclin D1 and p21, as well as PTEN/AKT/PI3K signaling pathways were actively modulated by miR-218 in HCC cells. The expression of endogenous HoxA10 was also down-regulated by miR-218 over expression, and silencing HoxA10 directly activated PTEN in HCC cells. CONCLUSION: Modulation of miR-218 actively affected HCC cancer cell development. The regulatory mechanism of miR-218 in HCC cells was acting through PTEN/AKT/PI3K pathway and possibly associated with HoxA10. PMID- 25120783 TI - Neutrophil-to-lymphocyte ratio (NLR) predicts mortality and adverse-outcomes after ST-segment elevation myocardial infarction in Chinese people. AB - Neutrophil-to-lymphocyte ratio (NLR) has been reported to predict cardiovascular risks and mortality in coronary artery diseases. We aimed to evaluate the capacity of NLR to predict long-term mortality in Chinese patients presenting with ST-segment elevation myocardial infarction (STEMI). We recorded NLR at admission, 24 or 72 hours after admission, and at discharge (14+/-2 days) of 692 patients presenting with STEMI at Xuanwu hospital, Beijing between 2002 and 2005, and assessed the capacity of NLR to predict mortality during follow up (median 9.43, interquartile range (IQR) 8.65-10.28 years). Backward stepwise multivariate Cox regression revealed that average inpatient NLR (NLRaverage) predicted all cause mortality (Hazard ratio 1.481) more accurately than absolute leukocyte and neutrophil counts (P<0.001). When patients were stratified into tertiles by NLRaverage (T1 NLR<3.16, T3 NLR>4.75), patients in T3 exhibited a 4.621-fold higher risk of mortality than patients in T1 (P=0.002). Patients in T3 had a significantly higher incidence of all-cause mortality (10.00%) than T1 (2.17%) and T2 (4.31%), cardiac-mortality (8.70%) than T1 (2.17%) and T2 (4.31%), hypotension (20.00%) than T1 (5.65%) and T2 (12.93%), arrhythmia (43.91%) than T1 (24.14%) and T2 (24.35%), and defibrillation (7.83%) than T1 (1.74%) and T2 (5.17%) in hospital; and suffered from higher mortality (46.09%) than T1 (9.13%) and T2 (29.74%), cardiac mortality (27.83%) than T1 (5.22%) and T2 (15.52%) and MACE events (36.52%) than T1 (13.04%) and T2 (31.9%) during long-term follow-up. Average NLR was a useful and powerful predictor of mortality and adverse-outcomes in Chinese patients presenting with STEMI. PMID- 25120784 TI - Clinicopathological features of hepatitis B virus recurrence after liver transplantation: eleven-year experience. AB - OBJECTIVE: We sought to investigate new changes in the clinical pathology of hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) in era of new nucleoside or nucleotide analogues. METHODS: One hundred and eighty four adult patients who underwent OLT for HBV-related end-stage liver disease between 1999 and 2010 were enrolled in this study. Of these patients, 156 received lamivudine (LAM) plus hepatitis B immune globulin (HBIG) and 28 were treated with LAM. The liver function, serologic parameters and HBV-DNA of the 184 recipients were followed up, and clinical pathological characteristics of grafts with HBV recurrence were examined in this study. RESULTS: One hundred and seventy nine (97%) were alive at their last follow-up and eleven (6%) had developed HBV recurrence at a median of 22 (range 6 to 46) months post-OLT. Two of the 11 recipients were detected with HBV-S gene mutation, and 5 were tested with YMDD mutation. Four recipients who died of irreversible graft dysfunction secondary to HBV recurrence, developed fibrosing cholestatic hepatitis (FCH) because of no effective antiviral agents available in the early stages of HBV recurrence after OLT. Six recipients who received adefovir (ADV) (and Entecavir, ETV) in the early stages of HBV recurrence after OLT achieved improvement in hepatic histology. CONCLUSIONS: HBV recurrence post-OLT could be controlled at an acceptable level for a long time and the recipients could achieve long-term survival by using new antiviral agents, instead of advancing into FCH in the short term after HBV recurrence. PMID- 25120785 TI - Dynamic metabolites profile of cerebral ischemia/reperfusion revealed by (1)H NMR based metabolomics contributes to potential biomarkers. AB - Current metabolomic studies of ischemic brain mainly attach importance on a certain ischemic period, are lack of data about dynamic metabolites in ischemic stroke process, especially early period. Thus, in this study, (1)H NMR spectroscopy was used to investigate biochemical changes in the early stages of rats' focal cerebral ischemia reperfusion (I/R) injury. Serum samples of 0, 0.5, 1, 3, 6, 12, 24 h of reperfusion, based on multivariate data analyses, were tested to analyze the changing of metabolites during the early disease process. Partial least squares-discriminant analysis scores plots of the (1)H NMR data revealed clear differences among the experiment groups. Combination the results of loading plot and t-test, we found that 13 metabolites were changed significantly. Among that, malonic acid and glycine are the most noticeable variable metabolites. Dramatic changed malonic acid and glycine most probably served as biomarkers in this study. These findings help us understand the biochemical metabolite changes in early ischemic stroke stages, especially different periods. That may be conducive to distinguish at-risk individuals, benefit early diagnosis and understand the dynamic pathogenesis of early cerebral ischemia. PMID- 25120786 TI - Immunohistochemical study for the origin of ductular reaction in chronic liver disease. AB - The appearance of proliferating bile ductular structures, which is called the "atypical ductular reaction" is frequently observed in various chronic liver diseases associated. However, the origin of these increased bile ductules has been a matter of controversy. In this study, we investigated the origin of ductular cells as an aspect of relation between epithelial to mesenchymal transition (EMT) and epithelial members of liver parenchyme, such as hepatocyte and cholangiocyte by immunohistochemical staining of human liver. Thirteen specimens of surgically resected liver with biliary cirrhosis were selected. Three sets of double immunohistochemical stains were done; Hep-Par 1 - cytokeratin 19 (CK19), Hep-Par 1 - alpha-sm ooth mus cle actin (alpha-SMA) and CK19 - alpha-SMA. As a result, we investigated the dual expression of the markers of hepatocyte and cholangiocyte in the same cell; in ductular cell and surrounding hepatocyte. However, there seems to be no dual expression of markers for EMT with epithelial markers. This study suggests a possibility of phenotypic change of mature hepatocyte into cholangiocyte. Future studies will be necessary to determine the role that proliferating cholangiocytes play in the pathogenesis of biliary fibrosis and how cholangiocytes interact with other cell types of the liver such as hepatic stellate cells or Kupffer cells. PMID- 25120787 TI - Prognostic value of hormone receptor status conversion following neoadjuvant chemotherapy in a series of operable breast cancer patients. AB - BACKGROUND: To investigate the prognostic value of hormone receptor (HR) status conversion after neoadjuvant chemotherapy (NAC) in patients with primary breast cancer. METHODS: 267 stage II-III breast cancer patients treated with NAC who had residual disease in the breast after NAC were retrospectively studied. The patients were divided into four groups based on the HR status: Group A, patients with HR-positive both before and after NAC; Group B, patients with HR status positive-to-negative change; Group C, patients with HR status negative-to positive change; Group D, patients with HR-negative both before and after NAC. Patients with positive HR status (regardless of before or after NAC) were treated with adjuvant endocrine therapy, and a survival analysis was performed. RESULTS: In total, 15.7% of patients had HR status change after NAC. progression-free survival (PFS) in Group A was similar to that in Group C (hazard ratio, 1.16; P = 0.652), but that in Group B was significantly lesser than that in Group A (hazard ratio, 6.88; P = 0.001), and that in Group C was significantly longer than that in Group D (hazard ratio, 6.88; P = 0.001). A similar pattern of results was obtained for overall survival (OS). CONCLUSIONS: The switch of HR status after NAC is remarkable for breast cancer. An HR switch may identify patients who would benefit from adjuvant endocrine therapy and impact the long-term outcome. PMID- 25120789 TI - Decreased LINE-1 methylation levels in aldosterone-producing adenoma. AB - PURPOSE: Abnormal global DNA methylation levels are associated with many diseases. In this study, we examined long interspersed nuclear elements-1 (LINE 1) methylation as a biomarker for abnormal global DNA methylation and aldosterone producing adenoma (APA). METHODS: Tissues from 25 APA and 6 normal adrenal glands (NAs) were analyzed for LINE-1 methylation by real-time methylation-specific polymerase chain reaction. The estimated LINE-1 methylation level was then tested for correlation with the clinicopathologic parameters of APA patients. RESULTS: The methylation index (MI) level for LINE-1 was 0.91 in NA samples and 0.77 in APA samples (P < 0.001). For the APA samples, there were no statistical correlations between the MI level and various clinicopathologic parameters such as gender (P = 0.07). CONCLUSION: LINE-1 methylation is significantly lower in APA samples than in NA samples. LINE-1 methylation is not correlated with the clinical characteristics of APA. PMID- 25120790 TI - Expression and clinical significance of cancer-testis genes in clear cell renal cell carcinoma. AB - Cancer-testis (CT) antigens, which are encoded by CT genes, have been recognized as a group of highly attractive targets for cancer immunotherapy. However, the expression and clinical relevance of CT genes in clear cell renal cell carcinoma (ccRCC) remains largely unknown. The present study aims to analyze the expression profile of 6 individual CT genes including MAGE-A1, MAGE-A3, MAGE-A12, cTAGE-1, cTAGE-2, and NY-ESO-1 in ccRCC and further investigate their possible correlations with clinicopathologic characteristics. The mRNA expressions of these CT genes were detected using reverse transcriptase-polymerase chain reaction (RT-PCR) in 105 ccRCC tissue samples (T1-2 in 70 samples, T3-4 in 35 samples; G1-2 in 65 samples, G3-4 in 40 samples) as well as the paired adjacent normal tissues. The most frequently expressed CT gene was MAGE-A3 (27.6%), followed by MAGE-A12 (23.8%), NY-ESO-1 (21%), MAGE-A1 (20%), cTAGE-1 (17.1%), and cTAGE-2 (14.3%). In contrast, no expression of CT genes was detected in the paired adjacent normal tissues. Furthermore, the MAGE-A3 protein expression was determined by Western blot and immunohistochemistry. MAGE-A3 protein was expressed in 21.9% ccRCC samples with a cytoplasmic staining pattern. No MAGE-A3 protein expression was found in the paired adjacent normal tissues. There was a significant correlation between MAGE-A3 expression at both mRNA (P =0.045) and protein (P = 0.03) levels with advanced stages of the disease. Taken together, CT genes may serve as promising targets of specific immunotherapy for ccRCC and particularly, MAGE-A3 may serve as a potential prognostic marker for ccRCC patients. PMID- 25120788 TI - Transcription factors related to epithelial mesenchymal transition in tumor center and margin in invasive lung adenocarcinoma. AB - The tumor microenvironment has many roles involving tumor progression, invasion and metastasis. The tumor cells at the tumor border loose epithelial properties and acquire mesenchymal features. This, epithelial-to-mesenchymal transition (EMT) has been suggested to be an important process for tissue and lymphovascular invasion. Pulmonary tissue samples from 15 patients with primary adenocarcinoma were evaluated with using immunofluorescence multi-staining the EMT-associated markers including E-cadherin and alpha-smooth muscle actin (alpha-SMA), and transcription factors including E-SNAIL and SLUG, and ZEB1. The data were analyzed in specific area, such as tumor center and tumor border. In this study we show that the invasive adenocarcinoma differentially expressed SNAIL and SLUG, and Zeb1 and it was associated with the loss of epithelial marker (E-cadherin) and gaining of mesenchymal marker (alpha-SMA) at the invasive border of lung carcinoma. The positive rates of SNAIL and ZEB1 were 26.7% and 0% in the tumor center and 40% and 20% in tumor margin, respectively. In addition, the expression of both SNAIL and ZEB1 at the border of tumor was observed in two cases (2/10). These two cases were associated with lymph node metastasis and advanced stage. The process of EMT has been suggested to be of prime importance for tissue and lymphovascular invasion. The process of EMT may be activated in the tumor border of lung adenocarcinoma. Related transcription factors, such as SNAIL and SLUG, and ZEB1, might be induced by paracrine effects of surrounded inflammatory cells and fibroblasts. PMID- 25120791 TI - Decreased RGS6 expression is associated with poor prognosis in pancreatic cancer patients. AB - Regulator of G-protein signaling 6 (RGS6), a member of a family of RGS proteins, has been reported to involve in multiple processes during tumor development. However, its role in pancreatic cancer has not been studied yet. In this study, we aimed to investigate the expression of RGS6 in pancreatic cancer and its role in predicting outcomes of patients with pancreatic cancer. We first measured the expression of RGS6 mRNA in 20 cases of tumor tissues and matched adjacent non tumorous tissues by quantitative real-time PCR and examined RGS6 protein by immunohistochemistry in tissue microarrays containing 90 tumor and 90 paired adjacent non-tumor tissues. Decreased RGS6 mRNA detected in primary tumor, compared with their non-tumor counterparts. In addition, decreased RGS6 protein expression was associated with tumor differentiation (P = 0.027), pT classification (P = 0.034), smoking status (P = 0.041) and a poor survival (P = 0.007). Cox proportional hazards regression modeling analysis revealed that lymph node metastasis (P = 0.001; hazard ratio, 2.347, 95% CI, 1.387-3.972), tumor differentiation (P = 0.015; hazard ratio, 0.505, 95% CI, 0.291-0.876) and RGS6 expression (P = 0.048; hazard ratio, 0.567, 95% CI, 0.324-0.994) were three independent prognostic factors. Taken together, these date demonstrate that RGS6 decreases in tumor tissue and may serve as a novel biomarker for outcomes in pancreatic cancer patients and be a potential therapeutic target potential therapeutic target. PMID- 25120794 TI - Complement membrane attack complex is related with immune-mediated necrotizing myopathy. AB - This study is to investigate the expression of complement membrane attack complex (C5b-9) in the skeletal muscle of patients with necrotizing myopathy (NM), and to investigate the relationship between C5b-9 and NM. Thirteen patients with NM and control patients with polymyositis and muscular dystrophy were enrolled in this study. Examinations including creatine kinase (CK) and L-lactate dehydrogenase (LDH) in the serum, electromyogram and muscle pathological examination were performed. C5b-9 expression in the skeletal muscle was determined by immunohistochemistry and analyzed by Image Plus Pro 6.0. C5b-9 expression was particularly prominent in necrotic muscle fibers, and also positive in blood vessels. C5b-9 diffusely expressed in vascular endothelial cells and smooth muscle layer. But the intensity was not related with the elevated level of serum CK. So, C5b-9 is strongly expressed in the necrotic muscle fiber and blood vessels, and may contribute to the pathogenesis of NM. PMID- 25120792 TI - A new 5-grading score in the diagnosis of prostate cancer with real-time elastography. AB - OBJECTIVE: To evaluate the clinical significance of transrectal real-time elastography (TRTE) in diagnosis of prostate cancer (PCA). METHODS: 195 patients with an elevated PSA level were enrolled in the study. A novel 5-grading score of prostate outer gland was applied by TRTE imaging. Receiver-operating characteristic curve (ROC) analyses were performed to assess the diagnostic performance of TRTE score. RESULTS: TRTE scores in patients with PCA and benign condition were 3.20 +/- 1.11 (range: 1-5) and 2.24 +/- 1.01 (range: 1-4), respectively (P < 0.001). The best cutoff value of TRTE score was 3, and the sensitivity, specificity, accuracy in the diagnosis were 68.6% (35/51), 69.4% (100/144) and 69.2% (135/195), respectively. The accuracy of TRTE in volume <= 30 ml group was significantly higher than that in the volume >= 50 ml group and the 30-50 ml group (76.9% vs. 65.0% and 76.9% vs. 71.4%, both P < 0.001). Accuracy of TRTE score was higher for those with PSA ranged 4-10 ng/ml than those with PSA > 10 ng/ml (85.3% vs. 66.7%, P = 0.002). CONCLUSION: TRTE score, a novel semi quantitative assessment of patients' prostate stiffness, can be served as a useful screening method for patients suspicious of PCA, especially those only having an elevated PSA level. PMID- 25120795 TI - Metastasis-associated colon cancer-1 is a novel prognostic marker for cervical cancer. AB - AIMS: To investigate metastasis associated in colon cancer 1 (MACC1) expression in cervical cancer. METHODS: One hundred and four paraffin-embedded cervical cancer specimens were immunohistochemically analyzed for MACC1 expression. The expression of MACC1 in 8 pairs of cervical cancer and adjacent normal cervical tissues were detected by Real-time PCR. RESULTS: MACC1 expression was upregulated in cervical cancer tissues compared with adjacent normal cervical tissues. Patients with higher MACC1 expression had shorter overall survival time, whereas those with lower ASAP1 expression survived longer (P = 0.029). Moreover, high expression of MACC1 was correlated with FIGO stage (P = 0.039) and lymph nodes metastasis (P = 0.003) of this disease. Multivariate analysis revealed that MACC1 was an independent prognostic factor (P = 0.043) for the overall survival of cervical cancer patients. CONCLUSION: Our study suggests that MACC1 may contribute to tumor development and progression in cervical cancer, and that MACC1 could be a useful marker for the prognosis of cervical cancer. PMID- 25120793 TI - Ileal interposition reduces blood glucose levels and decreases insulin resistance in a type 2 diabetes mellitus animal model by up-regulating glucagon-like peptide 1 and its receptor. AB - This study is to explore the possible mechanism of ileal interposition (IT) treatment of glycemic control of the type 2 diabetes mellitus (T2DM) by establishing an IT animal model. Twelve T2DM rats (GK rats) of 8-week old were divided into GK IT surgery group (GK-IT) and GK sham group (GK-Sham). Six Wistar rats were used as the non-T2DM sham group (WS-Sham). Enzyme-linked immunosorbent assay was used to detect plasma insulin concentration and fasting pancreas glucagon-like peptide-1 (GLP-1) concentration changes. Homeostasis model assessment of insulin resistance was used to quantitatively measure insulin resistance. Glucagon-like peptide-1 receptor (GLP-1R) expression was detected by Western blotting. IT significantly decreased fasting blood glucose level and the oral glucose tolerance, and reduced insulin resistance of GK rats by increasing GLP-1 concentration and GLP-1R levels. The postoperative pancreatic beta-cell apoptosis rate of GK-Sham group was significantly higher than those in the GK-IT group and the WS-Sham group. IT significantly reduces blood glucose and decreases insulin resistance by up-regulating GLP-1 concentrations and GLP-1R levels, which may contribute to insulin secretion of pancreatic beta-cells and decreases apoptosis of pancreatic beta-cell. PMID- 25120796 TI - Sex-specific association of the peptidase D gene rs731839 polymorphism and serum lipid levels in the Mulao and Han populations. AB - Little is known about the association of peptidase D (PEPD) gene rs731839 single nucleotide polymorphism (SNP) and serum lipid profiles in the Chinese population. The objective of the present study was to detect the association of the PEPD rs731839 SNP and serum lipid levels in the Mulao and Han populations. Genotyping of the PEPD rs731839 SNP was performed in 751 subjects of Mulao and 762 subjects of Han using polymerase chain reaction and restriction fragment length polymorphism and then confirmed by direct sequencing. The A allele carriers had higher serum high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI levels and lower triglyceride (TG) levels in Mulao; and higher HDL-C, low density lipoprotein cholesterol (LDL-C) and ApoAI levels in Han than the A allele non-carriers. Subgroup analyses showed that the A allele carriers had higher HDL C, ApoAI levels and lower TG levels in Mulao males but not in females; higher total cholesterol (TC), HDL-C, LDL-C and ApoAI levels in Han males; and higher TG, HDL-C and ApoAI levels in Han females than the A allele non-carriers. Serum lipid parameters were also correlated with several environmental factors in Mulao and Han populations, or in males and females in both ethnic groups. The association of the PEPD rs731839 SNP and serum lipid levels was different between the Mulao and Han populations, and between males and females in the both ethnic groups. There may be an ethnic- and/or sex-specific association of the PEPD rs731839 SNP and serum lipid levels in our study populations. PMID- 25120799 TI - Serum levels of microRNA-133b and microRNA-206 expression predict prognosis in patients with osteosarcoma. AB - The aim of the present study was to investigate whether the aberrant expression of microRNA (miR)-133b and miR-206 can be used as potential prognostic markers of human osteosarcoma. Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression levels of miR 133b and miR-206 in 100 pairs of osteosarcoma tissues and matched noncancerous bone tissues, and serum samples from 100 patients with osteosarcoma as well as in serum samples from 100 healthy controls. As a result, expression levels of miR 133b and miR-206 were both significantly decreased in osteosarcoma tissues and patients' sera (both P<0.001). Then, the downregulation of miR-133b and miR-206 both more frequently occurred in osteosarcoma patients with high tumor grade (both P=0.01), positive metastasis (both P<0.001) and recurrence (both P<0.001). Moreover, the patients with low miR-133b expression and low miR-206 expression both had shorter overall survival (OS, both P<0.001) and disease-free survival (DFS, both P<0.001) than those with high expressions. Of note, the OS and DFS of patients with combined low expression of miR-133b and miR-206 (miR-133b-low/miR 206-low) were the shortest (both P<0.001). Furthermore, low miR-133b expression, low miR-206 expression and conjoined expression of miR-133b/miR-206 were all independent prognostic factors for OS and DFS of osteosarcoma patients. Collectively, the aberrant expression of miR-133b and miR-206 may be implicated in tumorigenesis and tumor progression of osteosarcoma. More interestingly, detection of serum miR-133b and miR-206 expression could be further developed as novel, non-invasive and efficient markers for prognosis in patients with osteosarcomas. PMID- 25120797 TI - Expression of ALDH1 and TGFbeta2 in benign and malignant breast tumors and their prognostic implications. AB - The specific mechanism underlying the role of putative stem cell marker aldehyde dehydrogenase 1 (ALDH1) playing in development and progression of breast cancer is currently unclear. Transforming growth factor beta (TGFbeta) signaling pathway is reported to be activated in most cancers. Thus a study was initiated to explore possible differences and correlation of ALDH1 and TGFbeta2 expression in the most common malignant and benign tumors of the breast in Chinese women. Samples of 75 breast cancer tissues, 30 paracancerous normal tissues, and 39 fibroadenoma breast tissues were investigated for the expression of ALDH1 and TGFbeta2 using immunohistochemistry. The positive rates of ALDH1 and TGFbeta2 protein were 62.67% and 66.67%, respectively, in breast cancer tissues, which were significantly higher than that in normal fibroadenoma breast (P<0.05) and paracancerous tissues (P<0.01). ALDH1 and TGFbeta2 status were significantly associated with tumor histological grade and receptor status (P<0.05). Expression of ALDH1 was found to be positively correlative to TGFbeta2 in breast cancer (r = 0.33, P<0.01). Expression of both proteins remained significantly associated with reduced overall survival (OS) by univariate analysis (P<0.05). Multivariate Cox regression analysis showed that ALDH1 expression, tumor stage, and lymph node status are independent prognostic factors in invasive breast cancer patients. Thus ALDH1 and TGFbeta2 play important roles in the development of breast cancer. The ALDH1 phenotype is an independent predictor of poor prognosis, and TGFbeta2 signaling pathway activation might be involved in the pathological regulation of ALDH1 in breast cancer. PMID- 25120800 TI - Expression of O(6)-methylguanine DNA methyltransferase (MGMT) and its clinical significance in gastroenteropancreatic neuroendocrine neoplasm. AB - O(6)-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O(6)-alkylating agents. Until now, we know only little about the expression of MGMT in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). To study the expression of MGMT and its clinical significance in GEP-NEN, 174 specimens of GEP-NEN were examined, of which 152 specimens came from The First Affiliated Hospital, Sun Yat-sen University during October 1995 to November 2013, 22 specimens came from Peking Union Medical College Hospital during September 2004 to April 2010. MGMT protein was detected with EnVision immunohistochemical staining method. Clinicopathological factors were also collected and analyzed. We observed that the overall expression rate of MGMT was 83.9%. Over expression of MGMT protein was not associated with sex, age, functional status, primary tumor location, grading, classification, TNM stage and metastasis (P > 0.05). Kaplan-Meier analysis revealed that there was no significant difference in survival between MGMT-positive and MGMT-negative tumors of GEP-NEN patients (chi(2) = 0.887, P = 0.346). In multivariate analyses carried out by Cox proportional hazards regression model, MGMT expression was also not an independent predictors of survival. These results demonstrated that MGMT protein was highly expressed in GEP-NEN. MGMT deficiency rate was similar in pancreatic NEN and in gastrointestinal NEN. MGMT expression was not correlated with prognosis of GEP NEN. PMID- 25120798 TI - The absence of human papillomavirus in esophageal squamous cell carcinoma in East China. AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common types of tumors worldwide, particularly in China, and human papillomavirus (HPV) is thought to be a potential risk factor for this cancer. To determine whether this is true, we collected 177 formalin-fixed and paraffin-embedded ESCC samples from two hospitals. We screened for 23 different HPV genotypes using a human papillomavirus genotyping kit, which allowed us to amplify the L1 gene by polymerase chain reaction (PCR) and test for 23 HPV subtypes by reverse dot blot (RDB) on a single membrane. We also used immunohistochemistry (IHC) to detect the P16(INK4a) protein, the expression of which is linked to HPV E7 activity and which is used to diagnose cervical intraepithelial neoplasia. The genotyping results showed that only six samples were weakly positive for HPV: two for HPV16, two for HPV11 and two for HPV35, with no samples showing strong positive signals. The IHC results showed only five samples with diffuse positive staining, with the other samples being completely negative or having only focal positive signals, which were considered as negative. This study demonstrates that the HPV infection rate in ESCC samples is very low, suggesting that HPV is not the etiological cause of ESCC. PMID- 25120802 TI - HER2-positive mucinous adenocarcinomas of the ovary have an expansile invasive pattern associated with a favorable prognosis. AB - Ovarian primary mucinous adenocarcinomas (MACs) are refractory to conventional therapy. Biomarkers for ovarian MAC could facilitate prognosis and targeted therapy, but are not currently available. The expression of human epidermal growth factor 2 (HER-2) has been linked to enhanced survival of MAC patients and may hold potential as a biomarker, but this potential has not been sufficiently investigated. In this study, we examined the clinicopathological features of 46 cases of MAC and 36 cases of patients with mucinous borderline tumors (MBTs). The expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 were measured by immunohistochemistry and fluorescent in situ hybridization (FISH). Next, we compared the clinicopathological characteristics according to the HER2 expression profile. MBTs of the endocervical type tended to have simultaneous ER and PR expression (P = 0.0028) while MACs rarely showed ER or PR expression. HER2 expression was observed in 14 out of the 46 MACs (37.84%) and in none of the MBTs (P = 0.0002). HER2-positive MACs occurred approximately 10 years earlier than HER2-negative MACs (35.21 +/- 4.768 years compared to 46.78 +/- 1.977 years; P = 0.0105). All HER2-positive MACs demonstrated an expansile invasive pattern, while all MACs with infiltrative invasion pattern were HER2-negative (P = 0.0406). Kaplan-Meier survival analysis demonstrated a tendency for improved overall survival in HER2-positive MACs compared to HER2-negative MACs (P = 0.0389). In conclusion, HER2 overexpression in ovarian MACs is associated with an expansile, but not an infiltrative, invasion pattern and a favorable prognosis. Therefore, we suggest that HER2 may be a practical marker for histopathological categorization and a prognostic marker in ovarian MACs. PMID- 25120801 TI - High level of microtubule-associated protein light chain 3 predicts poor prognosis in resectable esophageal squamous cell carcinoma. AB - Microtubule-associated protein light chain 3 (LC3) is a key mediator bridging autophagy, apoptosis and differentiation. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) is still scanty. The purpose of this study was to investigate the clinical significance of LC3 by immunohistochemistry in a group of patients with ESCC treated with surgical resection. Tissue microarray that included 253 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of LC3 expression was analyzed statistically. The association of LC3 expression with the ESCC survival rate was assessed by Kaplan-Meier and Cox proportional-hazards regression. The results showed that the immunostaining of LC3 was distributed in cytoplasm and plasma-membrane. Significantly high LC3 expression was found in ESCC cells compared with that of normal esophageal epithelial cells. Patients with low expression of LC3 demonstrated higher overall survival compared with those with high expression of LC3 (mean of 71.1 months versus 55.5 months, P = 0.022). A similar result was observed for disease-free survival (mean of 68.7 months versus 51.8 months, P = 0.021). In subgroup analysis, LC3 expression could stratify pN0 patients with ESCC. Multivariate analysis showed that the level of LC3 expression was an independent prognostic factor in ESCC (RR = 1.407, P = 0.049). This paper shows high level of LC3 suggests poor prognosis for resectable ESCC patients. PMID- 25120803 TI - Bromodomain 4 protein is a predictor of survival for urothelial carcinoma of bladder. AB - BACKGROUND: Bromodomain 4 (BRD4) protein is a double bromodomain-containing protein that binds preferentially to acetylated chromatins. BRD4 is essential for cellular growth and has been implicated in cell cycle control, DNA replication and carcinogenesis. However, its expression profile and prognostic value in urothelial carcinoma of the bladder (UCB) have not been investigated. METHODS: Real-time quantitative PCR (qRT-PCR) and Western blot were used to explore BRD4 expression in UCBs and normal bladder tissues. Moreover immunohistochemistry (ICH) was used to detect the expression of BRD4 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. RESULTS: Up-regulated expression of BRD4 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blot when compared with their paired normal bladder tissues. Clinicopathological analysis was showed a significant correlation existed between the higher expression of BRD4 protein with the histological grade, lymph node metastasis and distant metastasis (P < 0.05); Survival analysis by Kaplan-Meier survival curve and log rank test demonstrated that elevated BRD4 expression in bladder cancer tissue predicted poorer overall survival (OS) compared with group in lower expression. Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of BRD4 was an independent prognostic factor in UCB. CONCLUSIONS: These results suggest that the aberrant expression of BRD4 in human UCB is possibly involved in the tumorigenesis and development, and the BRD4 protein could act as a potential biomarker for prognosis assessment of bladder cancer. Further studies on the cellular functions of BRD4 need to address these issues. PMID- 25120804 TI - Bortezomib-based chemotherapy regimens can improve response in newly diagnosed multiple myeloma patients with bcl-2 and survivin overexpression. AB - OBJECTIVE: To investigate the relationship between the Bcl-2 and survivin expression and the different regimens therapeutic efficacy newly diagnosed multiple myeloma (NDMM). METHODS: We retrospectively assessed the association of Bcl-2 and survivin expression with chemotherapeutic efficacy and prognosis in 59 NDMM patients in a single center. RESULTS: The positive expression rate for survivin and Bcl-2 was 35% and 74%, respectively. Survivin and Bcl-2 protein expression were not associated with clinical stage, suggesting that they are not related to tumor burden in NDMM. Bortezomib-based regimens were more effective in reducing tumor burden and achieving therapeutic (complete and partial) response compared with non-bortezomib-based regimens irrespective of Bcl-2 or survivin expression (P < 0.05). In cases with both negative Bcl-2 and survivin expression (Bcl-2(-)survivin(-)), the response to bortezomib and non-bortezomib-based regimens was similar (p = 0.429). Bcl-2 and survivin expression were not correlated with overall survival (OS); however, Bcl-2-survivin- cases showed a trend towards a longer OS (P = 0.078). CONCLUSION: We recommend bortezomib containing regimens for NDMM with single or double-positive Bcl-2 and survivin expression. PMID- 25120805 TI - DeltaNp63, CK5/6, TTF-1 and napsin A, a reliable panel to subtype non-small cell lung cancer in biopsy specimens. AB - Histopathological subtyping of nonsmall cell lung cancer (NSCLC) is currently important in selecting specific therapeutic agents. It can be challenging in distinguishing poorly differentiated lung adenocarcinoma (AC) from squamous cell carcinoma (SCC) on small biopsy samples. This study was aimed to evaluate the utility of a panel of immunohistochemical markers consisting of DeltaNp63 (p40), cytokeratins (CK) 5/6, thyroid transcription factor-1 (TTF-1) and napsin A (novel aspartic proteinase of the pepsin family) in subtyping poorly differentiated NSCLC. Forty-eight cases of NSCLC that could not be further classified by examination of hematoxylin-eosin (H&E)-stained slides on biopsy and had subsequent resection specimens were selected. Subtyping of the tumor was based on the resection specimen using the World Health Organization criteria. DeltaNp63 was expressed in all 16 SCCs (100%), and was negative in all ACs and LCCs. CK5/6 was positive in 13 of 16 SCCs (81%), and was negative in all ACs and LCCs. TTF-1 was positive in 20 of 25 ACs (80%) and 3 of 7 LCCs (43%), but none of 16 SCCs. Napsin A was positive in 16 of 25 ACs (64%) and was negative in all SCCs and LCCs. Our study shows that a panel including DeltaNp63, CK5/6, TTF-1, and napsin A allows correct subclassification of 39 of 48 cases of NSCLC on biopsy and may contribute to refine lung cancer classification in biopsy specimens, remarkably reducing the NSCLC-NOS (not otherwise specified) diagnostic category. PMID- 25120806 TI - Decreased expression of receptor tyrosine kinase of EphB1 protein in renal cell carcinomas. AB - Receptors tyrosine kinase of Eph superfamily plays an important role in human cancers. We previously found that EphB1 subtype is down-regulated in gastric cancer, colorectal cancer and ovary serous carcinoma. Fore the more, the decreased expression of EphB1 is related to invasion and metastasis in cancers. Although EphB1 has been revealed as an important receptor in cancers, our understanding of its roles in renal cell carcinoma (RCC) is limited. In the present study, using specific anit-EphB1 polyclonal antibody and immunohistochemistry, we evaluated EphB1 protein expression levels in RCC specimens surgically resected from 82 patients (including 62 conventional clear cell RCC, 10 papillary, and 10 chromophobic RCC cases). We found EphB1 protein is positively expressed in the epithelium of renal tubules. Decreased expression of EphB1 was found in all RCC carcinomas compared with expression in the normal epithelium of renal tubules. EphB1 protein moderately expressed in chromophobic RCC, weakly expressed in clear-cell RCC and negatively expressed in papillary RCC. Our results indicate that EphB1 may be involved in carcinogenesis of RCC, the molecular mechanisms of down-regulation of EphB1 including genetic and epigenetic alterations and the dedicated roles of EphB1 in occurrence and progress of RCC need to be explicated in next step. PMID- 25120807 TI - Association between mir-24 and mir-378 in formalin-fixed paraffin-embedded tissues of breast cancer. AB - BACKGROUND: MiR-24/378 is thought to be onco-miRNAs for their ability of enhancing tumor growth. The objective of this study was to evaluate the potential predictive value of miR-24/378 expression in formalin-fixed paraffin-embedded tissues of breast cancer patients. METHODS: The expression of miR-24/378 was examined in 101 breast cancer patients and 40 controls using real-time quantitative PCR. All statistical analyses were performed using SPSS16.0. RESULTS: We found that miR-24 and miR-378 were significantly up-regulated in breast cancer patients compared with controls (all P < 0.01). The expression levels of the two miRNAs were highly correlated with each other in breast cancer patients, with r = 0.778 between miR-24 and miR-378. Moreover, the two miRNAs exhibited great capability of discriminating between cancer patients and controls by ROC analysis. MiR-24 and miR-378 showed 0.79 and 0.807 AUC values respectively. CONCLUSIONS: Over-expression of miR-24 and miR-378 in FFPE tissue of breast cancer patients might conduct as an ideal source for biomarker discovery and validation in breast cancer patients. PMID- 25120808 TI - Synchronous primary triple carcinoma of thyroid and kidney accompanied by solitary fibrous tumor of the kidney: a unique case report. AB - Thyroid cancers coexisted with kidney cancer in a patient is an unusual event. Here, we described a case of 35-year-old woman with synchronous occurrence of primary papillary carcinoma and follicular carcinoma of the thyroid, accompanied by renal cell carcinoma and solitary fibrous tumor of the kidney, which has not been reported in literature to our best knowledge. Its clinical and pathological features, as well as the possible pathogenic factors were discussed. PMID- 25120809 TI - S-1 monotherapy as second line chemotherapy in advanced gastric cancer patients previously treated with cisplatin/infusional fluorouracil. AB - The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (ange: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination. PMID- 25120810 TI - C-kit and PDGFRA gene mutations in triple negative breast cancer. AB - In this study, we evaluated C-kit immunohistochemical expression and C-kit and platelet derived growth factor receptor A (PDGFRA) gene mutations in triple negative breast cancer. 171 cases were analyzed by immunohistochemical staining for the expression of C-kit and 45 cases, including 10 C-kit negative cases and 35 C-kit positive cases, were performed for C-kit gene mutations in exons 9, 11, 13 and 17 and PDGFRA gene mutations in exons 12 and 18. C-kit expression was detected in 42.1% of triple negative breast cancers. Only 1 activating mutation was detected in exon 11 of C-kit gene in 1 case. No activating mutations were found in the other 44 cases. C-kit expression is a frequent finding in triple negative breast cancers; 1 activating mutation which was also found in gastrointestinal stromal tumors was detected; a few cases might benefit from imatinib. PMID- 25120811 TI - Notch1 single nucleotide polymorphism rs3124591 is associated with the risk of development of invasive ductal breast carcinoma in a Chinese population. AB - Accumulated evidence has revealed the presence of Notch receptor polymorphisms in non-tumorous diseases; however, few studies have investigated the association of Notch polymorphisms with breast cancer risk. A total of 100 invasive ductal carcinoma (IDC) and 50 ductal carcinoma in situ (DCIS) patients and 100 usual ductal hyperplasia (UDH) controls were genotyped for the following Notch receptor single nucleotide polymorphisms (SNPs) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: Notch1, rs3124591; Notch2, rs11249433; Notch3, rs3815188, and rs1043994; and Notch4, rs367398, and rs520692. Immunohistochemistry was used to determine the effect of Notch polymorphisms on corresponding Notch protein expression in successfully genotyped patients. The frequency of rs3124591 TC genotype was significantly higher in IDC (24.7%, 20/81) and DCIS (30%, 12/40) patients than in UDH controls (8%, 8/97) (P = 0.002 and P = 0.011, respectively). However, the distribution of other SNP genotypes was not significantly different between IDC and DCIS patients and UDH controls. The frequency of TC genotype was significantly higher in poorly differentiated tumors than in well-differentiated and moderately differentiated tumors (P = 0.022). Importantly, a positive correlation between the rs3124591 TC genotype and high Notch1 protein expression was observed in DCIS patients (P = 0.043) but not in IDC patients. This is the first study to suggest an increased risk of IDC and DCIS of the breast for the Notch1 rs3124591 variant. Furthermore, given the inconsistent associations between the rs3124591 variant and Notch1 expression in IDC and DCIS, this variant may affect breast cancer risk through mechanisms in the latter stage other than alterations in Notch1 protein expression. PMID- 25120812 TI - Over-expression of p53, p21 and Cdc2 in histologically negative surgical margins is correlated with local recurrence of laryngeal squamous cell carcinoma. AB - The aim of this study was to explore the relationship between the expression of p53, p21 and Cdc2 in the early laryngeal cancer with negative pathological margins and its local recurrence. During 2004-2010, a total of 85 patients with early laryngeal cancer were selected in Tangshan Union Hospital, Hebei, China, and immunohistochemical method was used to detect the expression of p53, p21 and Cdc2 in the negative pathological margin tissues. All patients were followed up for two years to collect pathological data for evaluating the survival and tumor recurrence. Two years after surgery 14 of 85 patients with laryngeal cancer presented with recurrence (recurrent group), while 71 patients without recurrence (none recurrent group). The positive rate of p53, p21 and Cdc2 protein in laryngeal cancer tissues was 60.0% (51/85), 38.8% (33/85) and 70.6% (60/85), respectively, while that of the three proteins in the cancer adjacent tissues was 36.5% (31/85), 21.2% (18/85) and 29.4% (25/85), respectively. The differentiation and TNM stage of tumor had no correlation with the three proteins. The positive rate of p53 in the surgical margin of the recurrent group and non recurrent group was 71.4% (10/14) and 29.6% (21/71) (P = 0.003), that of p21 was 50.0% (7/14) and 15.5% (11/71), (P = 0.011) and Cdc2 was 57.1% (8/14) and 23.9% (17/71) (P = 0.030), respectively. In conclusion, p53, p21 and Cdc2 may be involved in the occurrence, development and recurrence of laryngeal squamous cell carcinoma. Overexpression of p53, p21 and Cdc2 in the surgical margin of early laryngeal cancer is closely related to local recurrence of tumor. PMID- 25120813 TI - Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma. AB - INTRODUCTION: Long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. lncRNA GAS5 has recently been identified to be involved in tumorigenesis of several cancers such as breast cancer, lung cancer and renal cancer. However, the regulation of GAS5 in hepatocellular carcinoma (HCC) has not yet been reported before. METHODS: Expression of GAS5 in tumor and their normal matched tissues was determined by quantitative real-time PCR in n = 71 HCC patients, and its association with overall survival of patients was analyzed by statistical analysis. RESULTS: The expression level of GAS5 was reduced in HCC in comparison to normal matched tissues (P < 0.05). It is also proved that GAS5 expression was to be associated with HCC tumor size, lymphnode metastasis and clinical stage (P < 0.05). In addition, the Kaplan-Meier survival curves revealed that low GAS5 expression was associated with poor prognosis in HCC patients. GAS5 expression was an independent prognostic marker of overall HCC patient survival in a multivariate analysis. CONCLUSIONS: The study proved for the first time that GAS5 down regulated in a majority of HCC patients. Our results indicated that GAS5 expression was an independent prognostic factor for patients with liver cancer, which might be a potential valuable biomarker for HCC. PMID- 25120814 TI - A comparison of ARMS and mutation specific IHC for common activating EGFR mutations analysis in small biopsy and cytology specimens of advanced non small cell lung cancer. AB - We have compared mutation analysis by Amplification Refractory Mutation System (ARMS) and epidermal growth factor receptor (EGFR) mutant-specific antibodies for their ability to detect two common activating EGFR mutations in a cohort of 115 advanced non-small cell lung cancer (NSCLC), including cytology material, core biopsy, and bronchoscopic biopsies. Assessment of EGFR mutation status was performed by using antibodies and ARMS assay specific to the two major forms of mutant EGFR, exon 19 deletion E746-A750 (c.2235_2249del15 or c.2236_2250del15, p. Glu746_Ala750 del) and exon 21 L858R point mutation (c.2573T>G, p.Leu858Arg). In this study the optimal buffer for antigen retrieval was sodium citrate (pH 6.0). Q score was used to evaluate the specific mutant EGFR proteins expression. Validation using clinical material showed deletions in exon 19 were detected in 19.1% and L858R mutation in 20% of all cases by ARMS assay. A cutoff value of score 1 was used as positive by IHC. No wild type cases were immuno-reactive. The antibodies performed well in cytology, core biopsies and bronchoscopic biopsies. There were only one false positive case using L858R IHC (sensitivity 100%, specificity 98.5%, positive predictive value 96%, negative predictive value 100%). All 23 E746-A750 exon 19 deletions identified by mutation analysis were positive by IHC. The sensitivity of exon 19 IHC for E746-A750 was 100%, specificity 100%, positive predictive value 100% and negative predictive value 100%. The result of the IHC stains was finely correlated with mutations status determined by ARMS assay. Although inferior to molecular genetic analysis of the EGFR gene, IHC is highly specific and sensitive for the targeted EGFR mutations. The antibodies are likely to be of clinical value in cases especially where limited tumor material is available, or in situations where molecular genetic analysis is not readily available. PMID- 25120815 TI - Urinary 6-sulfatoxymelatonin level in diabetic retinopathy patients with type 2 diabetes. AB - Melatonin is a powerful antioxidant. Decreased melatonin excretion has been reported to be associated with several oxidative stress-related diseases. The urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), has proved to be a very reliable index of melatonin production. The present study aims to evaluate the level of urinary aMT6s in patients with type 2 diabetes mellitus and diabetic retinopathy. Urine samples were collected from 10 patients with diabetes and no diabetic retinopathy (NDR), 19 patients with nonproliferative diabetic retinopathy (NPDR), 38 patients with proliferative diabetic retinopathy (PDR), and 16 subjects without diabetes mellitus, who served as controls. The level of aMT6s in specimens was assayed by a commercial aMT6s ELISA kit, creatinine levels were also measured for each sample to get urinary aMT6s/creatinine ratio. Creatinine-adjusted urinary aMT6s values were compared among four groups. The urinary aMT6s (mean +/- SD) levels were 9.95 +/- 2.42, 9.90 +/- 2.28, 8.40 +/- 1.84 and 5.58 +/- 1.33 ng/mg creatinine in the controls and in patients with NDR, NPDR, or PDR, respectively. The urinary aMT6s level of the PDR group was significantly lower than that of the control, NDR and DR groups. No significant difference was found among the control, NDR and DR groups. After adjustment for various factors (age, smoking, cancer, and coronary heart disease) that may influence the aMT6s level, the odds-ratio of urinary aMT6s comparing PDR patients to controls was 0.246 (95% confidence interval = 0.108-0.558, P = 0.001). Therefore, the urinary aMT6s level is significantly decreased in diabetic patients with PDR but not in diabetic patients without PDR, which indicates that decreased urinary aMT6s level may be associated with the pathogenesis of PDR. PMID- 25120816 TI - Immunohistochemical analysis using a BRAF V600E mutation specific antibody is highly sensitive and specific for the diagnosis of hairy cell leukemia. AB - Hairy cell leukemia (HCL) is usually diagnosed by morphology and flow cytometry studies. However, it is challenging sometimes to distinguish HCL from its mimics. Recently, the BRAF V600E mutation has been described as a disease-defining molecular marker for HCL which is present in nearly all cases of HCL but virtually absent in mimics of HCL. In this study, we investigated the possibility of using immunohistochemical detection of the BRAF V600E mutant protein to differentiate HCL from its mimics. A total of twenty-eight FFPE tissue specimens were studied, including HCL (n=12), HCL variant (HCL-v, n=3), splenic marginal zone lymphoma (SMZL, n=6), and other marginal zone lymphomas (MZL, n=7). Immunohistochemical studies were performed using a mouse monoclonal antibody (clone VE1, Spring Bioscience, CA) specific for BRAF V600E mutation. Molecularly confirmed BRAF V600E mutation positive and negative cases were used as the positive and negative controls respectively. All 12 cases of HCL showed cytoplasmic BRAF V600E protein expression in leukemia cells by immunohistochemical study regardless of tumor burden, whereas all cases of HCL mimics including HCL-v, SMZL, and MZL were negative for BRAF V600E protein. Using this BRAF V600E mutation specific antibody, this immunohistochemical study has 100% sensitivity and 100% specificity for the diagnosis of HCL in our cohort. In conclusion, immunohistochemical detection of the BRAF V600E mutant protein is highly sensitive and specific for the diagnosis of HCL. Compared to PCR or sequencing-based methodologies, immunohistochemistry is a relatively rapid and inexpensive alternative for the differential diagnosis between HCL and its mimics. PMID- 25120817 TI - Characteristics of demyelinating Charcot-Marie-Tooth disease with concurrent diabetes mellitus. AB - PURPOSE: Charcot-Marie-Tooth disease (CMT) is the most common type of inherited peripheral neuropathy and has a high degree of genetic heterogeneity. CMT with concurrent diabetes mellitus (DM) is rare. The purpose of this study is to explore the genetic, clinical and pathological characteristics of the patients with CMT and concurrent DM. METHODS: We investigated gene mutations (the peripheral myelin protein 22 gene, myelin protein zero gene, lipopolysaccharide induced tumor necrosis factor-alpha factor gene, early growth response gene and the neurofilament light chain gene loci) of a relatively large and typical Chinese family with CMT1 and concurrent DM2. From the literature, we also retrieved all reported families and single cases with CMT and concurrent DM. We comprehensively analyzed the characteristics of total 33 patients with CMT and concurrent DM, and further compared these characteristics with those of patients of diabetic peripheral neuropathy (DPN). RESULTS: Patients with CMT and concurrent DM had some relatively independent characteristics and pathogenic mechanisms. So we designated that kind of characteristic demyelinating CMT which accompanies DM as Yu-Xie syndrome (YXS), a new specific clinical subtype of CMT. CONCLUSION: CMT is an etiologic factor of DM, even though the intrinsic association between CMT and DM still remains further exploration. PMID- 25120818 TI - Lack of association between rs3807989 in cav1 and atrial fibrillation. AB - BACKGROUND: A novel gene Caveolin-1(CAV1) was identified to be susceptibility to PR interval and also associated with atrial fibrillation (AF) in two Genome wide associations studies (GWAS) studies in European ancestry. The purpose of this study was to determine the association of the SNPs in CAV1 gene of rs3807989 with AF in Chinese Han patients. METHODS AND RESULTS: We attempted a replication in a cohort of 839 Chinese AF patients and 1215 healthy controls using melting temperature shift allele-specific genotyping analysis. One SNP in CAV1 (rs3807989) was genotyped. The final study cohort consisted of 839 AF patients and 1215 healthy controls. No significant association was detected between rs3807989 and AF in a Chinese Han population (allelic P-adj = 0.828 with OR = 1.02; genotypic P-adj = 0.815, 0.405, 0.760 with a dominant model, recessive model, and additive model). After logistic regression with multiple covariates, the association remained non-significant with adjusted P value 0.828. When the AF cases were further divided into lone AF (31.5%) and other types of AF (68.5%), no significant association was found between rs3807989 and lone AF (P-adj = 0.929 with OR = 0.990) and other types of AF (P-adj = 0.597 with OR = 1.060). CONCLUSION: The SNP rs3807989 in CAV1 gene is not associated with AF or lone AF in our studies, which suggests that the SNP rs3807989 in CAV1 may not be a risk factor for AF in Chinese Han population. PMID- 25120819 TI - Associated liver enzymes with hyperlipidemic profile in type 2 diabetes patients. AB - Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and is associated with dyslipidemia and disturbed liver function. Aim of the present work is to assess the liver enzymes and to find its association with hyperlipidemic profile in T2DM. Total of 157 subjects were studied and divided into two groups; diabetes (n=81) and non-diabetes (n=76). Various biochemical parameters like fasting glucose, post prandial glucose, HbA1c, total cholesterol (TC), triglycerides (Tg), high density lipoprotein cholesterol (HDL-C), alanine amino transferase (ALT), aspartate amino transferase (AST) and gamma-glutamyl transferase (GGT) were analyzed by ROCHE module Cobas 6000 (C501 & C601) analyzer, kits were procured by ROCHE diagnostics. Low density lipoprotein cholesterol (LDL-C) was estimated by Freidwald's formula. Statistical analysis was performed by applying student t test and Pearson's correlation coefficient, at 0.0001 and 0.05 level of significance, respectively. All the glycemic control parameters, lipid profile parameters except HDL-C and liver enzymes were found increased in diabetes group and significantly differ from non-diabetes group (p>0.0001). ALT showed significant positive correlation with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and GGT at p>0.05. AST showed very weak relation with all parameters while GGT was positively associated with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and ALT at p>0.05. In conclusion, T2DM incline to elevate liver enzymes, especially ALT and GGT were of significance. Routine screening of ALT and GGT in T2DM patients may assists early detection of liver abnormalities and to arrest the progress of disease. PMID- 25120820 TI - Clear cell changes in mucinous tubular and spindle cell carcinoma: cytoplasmic pallor/clearing within tubules, vacuoles or hybrid conventional clear cell carcinoma of kidney? AB - Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and recently recognized subtype of renal cell carcinoma (RCC). Apart from the classic morphology comprising conventional three components, there exist a large number of non-classic morphological variants of MTSCC, which make it necessity to differentiate from other RCC. Herein, we report two non-classic morphological variants of MTSCC. Case 1, a 85 years old man, showed numerous vacuoles among inherent components and cytoplasmic pallor/clearing within tubules mimicking conventional clear cell RCC with a 8.5 years follow-up, while Case 2 indicated a "mucin-poor" MTSCC associated with simultaneous conventional clear cell RCC at her age of 73 years. Until now Case 1 carries the longest disease-free survival reported in literature since MTSCC was defined and ranks the oldest since reported in literature, while Case 2 is the first report of "mucin-poor" MTSCC associated with simultaneous conventional clear cell RCC. Now, since no biomarkers or imagining tools but pathological examination can confirm the diagnosis of MTSCC, the management is always following the guideline of RCC in clinical practice. Generally, most reports consider it as a good prognosis disease, but sarcomatoid variant, even classic subtype can progress rapidly to life-threatening disease. PMID- 25120821 TI - Pathogenesis of fulminant monkeypox with bacterial sepsis after experimental infection with West African monkeypox virus in a cynomolgus monkey. AB - The pathogenesis of severe human monkeypox, which causes systemic and fulminant infections, is not clear. This study presents a case repot of fulminant monkeypox with bacterial sepsis after experimental infection with monkeypox virus in a cynomolgus monkey (Macaca fascicularis). In our previous study (Saijo et al., 2009, J Gen Virol), two cynomolgus monkeys became moribund after experimental infection with monkeypox virus Liberia strain, West African strain. One exhibited typical monkeypox-related papulovesicular lesions. The other monkey presented fulminant clinical symptoms with a characteristic flat red rash similar to that found in smallpox, which is associated with extremely high fatality rates. In this study, we found that the monkey with flat red rash had high levels of viremia and neutropenia, as well as high plasma levels of pro-inflammatory cytokines and chemokines compared with the other monkey. Monkeypox virus replicates in epithelial cells and macrophages in various organs. Sepsis due to Gram-positive cocci was confirmed histopathologically in the monkey with flat red rash. The lack of inflammatory response in the lesion suggested that the monkey with sepsis experienced strong immune suppression during the viral infection. The neutropenia and excessive inflammatory cytokine responses indicate that neutrophils play key roles in the pathogenesis of systemic and fulminant human monkeypox virus infections with sepsis. PMID- 25120822 TI - Spontaneous regression of breast cancer with axillary lymph node metastasis: a case report and review of literature. AB - Spontaneous regression (SR) of cancer is a rare but well-documented biological phenomenon. However, the mechanism remains to be elucidated. We herein report a case of the SR of breast cancer at both the primary site and metastatic axillary lymph node with spontaneously-induced T cell-mediated immunological responses. A 52-year-old female with a lump in the left axilla was diagnosed to have a small breast carcinoma with a distinct axillary lymph node metastasis. During the preoperative systemic examination, she was diagnosed to have severe type 2 diabetes mellitus, was treated with insulin, and the hyperglycemia was normalized after one month. Surgery for left breast cancer was then performed. The postoperative histopathological examination revealed the SR of breast cancer at both the primary site and metastatic axillary lymph node. Immunohistochemical studies revealed that estrogen receptor positive, AE1/AE3-positive ductal carcinoma completely underwent necrosis associated with extensive infiltration of CD3-positive T cells in the tumor nodule in the lymph node. In addition, primary ductal carcinoma cells also underwent single cell necrosis with infiltration of T cells with lymph follicle-like organization of B cells in the mammary gland. The features were suggestive that the tumor eradication in the metastatic lymph node and regression of the primary ductal carcinoma could be due to host T cell response to the ductal carcinoma. As far as we know it is the first report that shows the spontaneous regression of breast cancer, probably due to the spontaneously-induced T cell response. PMID- 25120823 TI - Primary platelet-derived growth factor-producing, spindle-shaped diffuse large B cell lymphoma of the skull: a case report and literature review. AB - A 39-year-old woman with a right frontal mass underwent a cranial bone tumor biopsy. Histopathologic examination of hematoxylin and eosin-stained slides showed spindle-shaped tumor cells in a storiform pattern, appearing somewhat like a sarcoma. However, the tumor cells were CD20-positive by immunohistochemical staining. Therefore, a diagnosis of spindle-shaped diffuse large B-cell lymphoma (Sp-DLBCL) was made. There have been at least 35 cases of Sp-DLBCL documented in the literature, and most were of the germinal center type, while the present case is the first report of a vimentin-positive primary Sp-DLBCL of the skull. The DLBCL in this case was immunohistochemically stained for six representative cytokines that might give rise to fibrosis, due to the evidence of fibroblastic proliferation. The DLBCL cells were positive for platelet-derived growth factor (PDGF), and some cells were also positive for tumor necrosis factor (TNF) alpha. Based on these findings, it was inferred that the PDGF and TNFalpha produced by DLBCL cells induced fibroblastic proliferation. The resultant conspicuous fibrosis caused interfibrous impingement on the DLBCL cells, which deformed them into a spindle shape. The present case is the first reported case of a PDGF producing Sp-DLBCL. PMID- 25120824 TI - A case of blastic plasmacytoid dendritic cell neoplasm with ecchymotic lesions on the whole body. AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from plasmacytoid dendritic cell precursors is a very rare, and characterized by cutaneous and bone marrow involvement and leukemic spread. The neoplasm presents with an aggressive behavior, and the clinical findings include cytopenia, particularly thrombocytopenia. The tumor cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and CD123, which are markers of plasmacytoid dendritic cells, and negative for Epstein-Barr virus (EBV). From this point of view, a 71-year-old man who was initially found to have a cutaneous mass on his face and thorax was reported here, and initially was diagnosed as "eczema". The skin rashes then became aggravated on a trial of low dose topical corticosteroid for 2 months. According to skin biopsy, the tumor cells reveal an immature blastic appearance and positive for CD4 and CD56, negative for CD3, CD20, indicating a diagnosis of BPDCN. Here, we report the dismal course of a patient with BPDCN without accepting further therapy, and only survived 3 months. PMID- 25120825 TI - Plasmablastic lymphoma following combination treatment with fludarabine and rituximab for nongastric mucosa-associated lymphoid tissue lymphoma: a case report and review of literature. AB - Plasmablastic lymphoma (PBL) is an uncommon malignancy which predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients. Sporadic cases have been published describing PBL in immunocompetent patients as well as in immunodeficient patients following immunosuppressive therapy or transplantation. We hereby reported a case of PBL in a 69-year-old, HIV-negative male subjected to combination treatment with fludarabine and rituximab for nongastric mucosa-associated lymphoid tissue (MALT) lymphoma. The diagnosis of PBL was made with tumor cells of immunoblasts or plasmablasts morphology strongly positive for MUM-1, EMA and CD138, and partly positive for CD38, and negative for CD20, BCL-6, and CD56, and approximately 80% of which were positive for Ki-67. The case presented PBL after MALT, and a history of chemotherapy including fludarabine and rituximab led to the potential immunocompromised state. The patient died 5 months after the diagnosis of PBL. PMID- 25120826 TI - Mullerianosis and endosalpingiosis of the urinary bladder: report of two cases with review of the literature. AB - Mullerianosis of the urinary bladder is an extremely rare benign condition, characterized by the presence of a mixture of at least two mullerian-derived components, and endosalpingiosis is also an extremely rare condition, characterized by the presence of tubal-type epithelium. In this report, we describe the 17(th) case of mullerianosis and 5(th) case of endosalpingiosis of the urinary bladder. A 39-year-old Japanese female presented with menstrual hematuria and was found to have a polypoid lesion in the posterior wall of the urinary bladder. Histopathological study demonstrated variably-sized dilated tubular glands in the lamina propria and muscularis propria. These dilated glands were covered by ciliated cuboidal cells, and some of them were covered by columnar cells with intracytoplasmic mucin. Moreover, a tiny focus of endometrial tissues was also present. Immunohistochemically, these glandular cells were positive for estrogen receptor. Accordingly, a diagnosis of mullerianosis was made. The second case was a 37-year-old Japanese female, who was found to have a polypoid lesion in the posterior wall of the bladder. Dilated tubular glands were covered by ciliated cells in the lamina propria and muscularis propria. Neither endocervical nor endometrial tissues were observed. Immunohistochemically, these ciliated cells were positive for estrogen receptor. Accordingly, a diagnosis of endosalpingiosis was made. Our analysis revealed that these two conditions mainly affect premenopausal females and occur exclusively in the posterior wall. Although the pathogenesis remains completely unresolved, a metaplastic theory is favored. The recognition of these two conditions is important because they can mimic invasive adenocarcinoma. PMID- 25120828 TI - Low-grade endometrioid carcinoma of the ovary associated with undifferentiated carcinoma: case report and review of the literature. AB - The association of low-grade endometrioid carcinoma with undifferentiated carcinoma (UC) was first reported in endometrium carcinoma, termed with dedifferentiated carcinoma (DC). However, the coexistence of low-grade endometrioid carcinoma (LGEC) or serous carcinoma (LGSC) with UC has received minimal attention in ovary, and the behavior of this kind of neoplasm remains at further discussion. In this study, we reported a case of low-grade ovarian endometrioid carcinoma associated with UC and reviewed another four cases previously reported. We found a histological continuity between the LGEC and UC components in H&E section, which suggested a dedifferentiation from LGEC to UC components. In summary, this kind of pathological type has aggressive behavior and these patients have very poor prognosis regardless of the amount of undifferentiated carcinoma. PMID- 25120827 TI - Ectopic cortisol-producing adrenocortical adenoma in the renal hilum: histopathological features and steroidogenic enzyme profile. AB - Ectopic cortisol-producing adrenocortical adenomas (CPA) are extremely rare, and only four cases have previously been reported so far but the tumors were not ultrastructurally studied. Presented in this paper is the fifth case with ectopic CPA which was extensively examined to gain deeper insights in terms of the histopathological features and steroidogenic enzyme profile of the tumor. A 53 year-old woman complained of accidental discovery of left renal mass. She had a 5 year history of hypertension, weight gain, moon face, thin skin and systemic edema. These symptoms completely relieved after the tumor removal. Two years later, the above symptoms recurred, and a recurrent tumor was revealed in left renal hilum. The tumor was removed completely with relief of her symptoms of Cushing's syndrome. Histologically and ultrastructurally, the tumor was composed of compact cells and clear cells, and the former was prominent, suggesting an active secretory function of the tumor. The adenoma tissue showed a strong immunostaining for Melan-A, 3beta-hydroxysteroid dehydrogenase (HSD3B2) and 17alpha-hydroxylase1 (CYP17A1). Expression pattern for 11beta-hydroxylase 1 (CYP11B1), 11beta-hydroxylase 2 (CYP11B2), CYP17 and HSD3B2 mRNA in ectopic CPA was similar to that in the adrenal CPA. In conclusion, in terms of histopathological characteristic and steroidogenic enzyme profile, ectopic CPA is similar to adrenal CPA, suggesting that they are of identical cell origin. PMID- 25120829 TI - Sarcoidal granulomas in the mediastinal lymph nodes after treatment for marginal zone lymphoma of the esophagus: report of a case with review of the concept of the sarcoidosis-lymphoma syndrome. AB - Patients with sarcoidosis have a high risk of development of malignant lymphoma, and this association was coined the term "sarcoidosis-lymphoma syndrome". Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct clinicopathological entity, and the stomach is the most common site. The occurrence of this type of lymphoma in the esophagus is extremely rare. In this report, we describe the first documented case of sarcoidal granulomas in the mediastinal lymph nodes after treatment for MALT lymphoma of the esophagus. A 60-year-old Japanese female was found to have a submucosal tumor in the esophagus. Histopathological study revealed proliferation of small- to medium-sized lymphoid cells with convoluted nuclei, and immunohistochemically, these lymphoid cells were diffusely positive for CD20, bcl 2, and MUM1. R-CHOP therapy was performed, which led to tumor remission. Two years later, swelling of the mediastinal lymph nodes was detected. Histopathological study of the lymph nodes revealed presence of variably-sized epithelioid granulomas without caseating necrosis but no malignant lymphoma was noted. Sarcoidal granulomas can be observed in patients with malignant tumors including malignant lymphoma and carcinoma without history of systemic sarcoidosis. It is important to recognize that systemic sarcoidosis and sarcoidal reaction without evidence of systemic disease can occur after development of malignant lymphoma, therefore, sarcoidal reaction must be included in the differential diagnostic consideration of recurrent malignant lymphoma. PMID- 25120830 TI - Posterior reversible encephalopathy syndrome in a child with steroid-resistant nephrotic syndrome: a case report and review of literature. AB - Posterior reversible encephalopathy syndrome (PRES) is a rare and serious syndrome of central nervous system that can develop in both adults and children. It is characterized by acute onset of headache, confusion, seizures or focal neurological deficits along with radiological findings of white matter abnormalities in the parietal and occipital lobes. In the past ten years, this syndrome has been described mainly in adults, rare in children. Here, we report a case of PRES presenting in a 12-year-old girl with steroid-resistant nephrotic syndrome. Her neurological symptom was rapidly recovered after control of hypertension without discontinuation of cyclosporine A. PMID- 25120831 TI - A case of (123)I-MIBG scintigram-negative functioning pheochromocytoma: immunohistochemical and molecular analysis with review of literature. AB - A 70-year-old Japanese woman was referred to our hospital due to hyperhidrosis and rapid weight loss of 10 kg in a month. A lump measuring 26 mm in diameter was detected in the left adrenal gland by computed tomography. Biochemical tests showed high levels of serum and urinary norepinephrine and epinephrine. However, a (123)I-MIBG scintigram failed to detect any accumulation in the left adrenal tumor. A left adrenalectomy was performed post clinical diagnosis of (123)I-MIBG negative pheochromocytoma. Microscopically, the tumor exhibited pheochromocytoma compatible features. Immunohistochemical analysis revealed low expression of VMAT1 in the tumor compared to the normal, surrounding tissue. To test for a possible genetic alteration of the monoamine transporter genes, we performed whole-exome sequencing of the VMAT1, VMAT2, and NET genes in the tumor. No significant base sequence substitution or deletion/insertion was found in any transporter. This suggests that MIBG negativity is caused by a change that is independent of the base sequence abnormalities, such as an epigenetic change. Furthermore, a retrospective literature review of (123)I-MIBG negative scintigraphy cases indicates that a negative finding in the (123)I-MIBG scintigram is frequently associated with metastatic pheochromocytomas or SDHB mutations. However, a SDHB/D gene mutation has not been identified in the reported case. Although the patient needs careful monitoring following the surgery, to date she has been disease free for 12 months. This study could not find clear reasons for negative conversion, however, investigations of the negative conversion mechanism might reveal significant insights towards the improvement of patient survival. PMID- 25120832 TI - Multiple genital tract tumors and mucinous adenocarcinoma of colon in a woman with Peutz-Jeghers syndrome: a case report and review of literatures. AB - We report a very rare case of Peutz-Jeghers syndrome (PJS) composed of multiple genital tract tumors and mucinous adenocarcinoma. A 46-year-old woman presented to our hospital with lower abdominal pain resulting from PJS involves sex cord tumor with annular tubules (SCTAT), ovarian mucinous tumor, ovarian serous tumor, mucinous adenocarcinoma of colon. The CEA concentration is high before surgery, and decreases after the surgery and subsequent chemoradiotherapy. This case demonstrates a classic clinical presentation of a patient with PJS. PJS patients have increased risk of malignancy and early detection and regular surveillance of the high-risk patients with PJS is crucial. Surgery may be required for obstructive gastrointestinal lesions as well as those exhibiting malignant degeneration. PMID- 25120833 TI - Immunohistochemical results of HER2/neu protein expression assessed by rabbit monoclonal antibodies SP3 and 4B5 in colorectal carcinomas. AB - HER2/neu is an efficient target for cancer therapy. However, reports about its overexpression rate in colorectal carcinomas showed wide variability. This study aims to investigate HER2/neu expression in colorectal carcinomas using these two rabbit monoclonal HER2/neu antibodies, and to clarify the relationship between protein overexpression and gene amplification of HER2/neu and their clinicopathologic importance. Tissue microarray was performed from sections of 106 cases colorectal carcinomas. Their clinical data, including gender, age, stage, recurrence, lymph node metastasis, and follow-ups were collected. Immunohistochemistry for rabbit monoclonal antibody SP3 and 4B5 were performed, Fluorescent in situ hybridization was applied to detect the amplification of HER2/neu gene. The HER2/neu overexpression of (2+ and 3+) in our results were seen in 7.5% (8/106) for 4B5 and 3.8% (4/106) for SP3 respectively, the HER2/neu amplification was in 2.8% (3/106). All cases of overexpression for SP3 were included by those for 4B5. Both antibodies stained 3 cases of HER2/neu 3+, and FISH confirmed HER2/neu amplification did occurred in these cases. In our study, 4B5 was more sensitive to detect HER2/neu of colorectal carcinoma than SP3. 2.8% patients with colorectal patients might benefit from anti-HER2/neu therapy. PMID- 25120834 TI - Malignant solitary fibrous tumor of breast: a rare case report. AB - Solitary fibrous tumor (SFT) is rare mesenchymal neoplasm that has been originally and most often documented in the pleura. Recently, the ubiquitous nature of the SFT has been recognized with reports of involvement of numerous sites all over the body such as: upper respiratory tract, somatic tissue, mediastinum, head, and neck. Less than 10 cases SFT of breast have been reported. Herein, we presented a 52-year-old Asian female with SFT of breast, this tumor showed predominant malignant features. To our knowledge, SFT of breast with such malignant evidence is extremely rare. PMID- 25120835 TI - A case of lupus-like glomerulonephritis in an HIV patient with nephrotic range proteinuria, purpura, and elevated IgA level. AB - Human immunodeficiency virus (HIV) infection is growing medical concern worldwide. There are many types of glomerulonephritis which are associated with HIV infection. We report a case of a 53-year-old Korean man with an HIV infection, who was developed nephritic range proteinuria and purpura with elevated IgA level rasing a possibility of Henoch-Scholein Purpura (H-S purpura). However, renal biopsy showed "lupus-like feature" glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. Although baseline renal function was maintained without further need for maintenance dialysis following anti-retroviral therapy (ART) and steroid, patient died from uncontrolled gastrointestinal bleeding. PMID- 25120836 TI - Mixed granular cell astrocytoma and fibrosarcoma of the brain: a case report. AB - We describe a rare primary mixed granular cell astrocytoma and fibrosarcoma neoplasm, occurring in a 52-year-old female, with morphologic, immunohistochemical and molecular genetic features, whose tumor was entirely composed of granular cells and fibrosarcoma competent. This represents, to the best of our knowledge, the first report of the mixed granular cell astrocytoma and fibrosarcoma neoplasm. Moreover, two parts forming a complex arrangement that excluded it being assessed as a coincidental collision tumor. We discuss the relationship of two parts of this rare tumor by fluorescence in situ hybridization (FISH). Sarcomatous components in this tumor had the same aberrations of chromosomes to the gliomatous components of neoplasms, consisting of 1p 19q loss and no evidence of PTEN allele loss and amplification of EGFR. It was suggested that the sarcomatous component may be derived from glioma cells i this case. PMID- 25120837 TI - Plasmablastic lasmablastic lymphoma of the duodenal and jejunum. AB - Plasmablastic lymphoma (PBL) is a rare B-cell neoplasm with an aggressive clinical behavior that predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients. HIV-negative PBL has not been extensively reported. A 65-year-old female presented with anemia, who was HIV negative. Gastrointestinal fiberscope (GIF), and colon fiberscope (CF) were performed. However, we could not detect the bleeding sites. We detected the tumor by capsule endoscopy, and obtained the tumor cells from the duodenal and jejunal sites. The neoplastic cells were diffusely positive for CD56, epithelial membrane (EMA), CD4, lambda, and EBV-encoded RNA1 (EBER1) and partially positive for CD138 and CD79a. This patient was diagnosed as PBL. The small intestine is a rare extra oral site of involvement in PBL patients, and only four cases in HIV-negative patients have been reported. PMID- 25120838 TI - Primary follicular lymphoma of the spleen incidentally found in a patient with alcohol- and hepatitis C-related liver cirrhosis. AB - Primary splenic lymphoma is rare as non-Hodgkin lymphomas. Splenic infiltration of lymphoma cells may cause splenomegaly in many cases. However, splenomegaly is caused not only by tumor involvement but also by non-tumorous disorders. One of the most prevalent non-neoplastic causes is portal hypertension mostly due to liver cirrhosis. On the other hand, liver cirrhosis may underlie various extrahepatic manifestations including development of B-cell non-Hodgkin lymphomas. Here, we report a case of primary follicular lymphoma of the spleen in a patient with liver cirrhosis related to hepatitis C and alcohol. The lymphoma was incidentally found in an enlarged spleen resected palliatively to alleviate symptomatic pancytopenia of the patient. The main characteristic of our case is an incidental finding of a rare situation brought by careful pathological examination. Our case illustrates the importance to recognize a possibility of co occurrence of chronic liver disease and extrahepatic lymphoma. PMID- 25120839 TI - Sarcomatoid carcinoma involving the nasal cavity and paranasal sinus: a rare and highly progressive tumor. AB - Sarcomatoid carcinoma of nasal cavity and paranasal sinuses is an extremely rare malignant neoplasm. We report a case of sarcomatoid carcinoma arising in the left side nasal cavity and paranasal sinuses in a 65-year-old man who was hospitalized for left-side nasal epistaxis, odor sensation. Histopathologic examination revealed the tumor was composed of pleomorphic spindle and round cells with frequent mitosis, and no carcinomatous component was recognized. Immunohistochemistry revealed coexpression of cytokeratin and vimentin by the tumor cells, whereas expressions of EMA, S-100, HMB-45, Melan-A, LCA, MyoD1, CD34, CK7, F8 and desmin were negative. The diagnosis was sarcomatoid carcinoma of nasal cavity and paranasal sinuses. The neoplasm was partial resected by nasal endoscopic surgery following chemoradiation therapy immediately. But it was still progressing rapidly, and had a poor prognosis. PMID- 25120840 TI - Diagnostic problems related to acute fibrinous and organizing pneumonia: misdiagnosis in 2 cases of lung consolidation and occupying lesions. AB - Acute fibrinous and organizing pneumonia (AFOP) is a histological pattern characterized by intra-alveolus fibrinous deposition accompanied with a spectrum of clinical condition. It also presents in other types of lung lesions, thus renders risks to its diagnosis with small biopsies. Here we present 2 cases of lung consolidation and occupying lesions with typical histological presentation of AFOP. One case is tuberculosis presented as massive lung consolidation, initially treated as AFOP, and eventually progressed to bilateral military tuberculosis. The other case presented an occupying mass in the lung which was initially suspected to be an inflammatory mass with AFOP. Lobectomy revealed a poorly-differentiated adenocarcinoma, with AFOP pattern present in the peripheral tissues of the neoplastic mass. In conclusion, we suggest that it is not preferable to diagnose idiopathic AFOP in lung consolidation and occupying lesions before excluding other types of lesions. The diagnostic significance of AFOP should be deliberated. PMID- 25120841 TI - Blasts-more than meets the eye: evaluation of post-induction day 21 bone marrow in CBFB rearranged acute leukemia. AB - Induction chemotherapy is often the first therapeutic intervention for acute myeloid leukemia (AML). Evaluation of post induction bone marrow provides critical information for clinical management; in general increased blast countsor increased marrow cellularity is an ominous sign, suggestive of ineffective therapy, and may warrant additional rounds of chemotherapy. However, increased blasts alone are not necessarily predictive of recurrent/persistent disease. Here we report a very unusual observation in a case of AML with a core binding factor beta (CBFB) rearrangement. In this case the day 21 post-induction marrow biopsy showed a high blast count (approximately 20%), however,subsequent fluorescence in situ hybridization studies were negative for CBFB rearrangement. We compared this finding to post-induction marrows from a series of 6 AML cases with CBFB rearrangements, none of which showed an increased blast count. This case illustrates that increased blast counts, even those comprising 20% of cells, are not de facto evidence of induction failure, and that correlation with ancillary studies such as fluorescence in-situhybridization should be used to distinguish a persistent neoplastic clone, from a brisk marrow recovery. PMID- 25120842 TI - Intraneural malignant perineurioma: a case report and review of literature. AB - The great majority of malignant peripheral nerve sheath tumors (MPNSTs) exhibit Schwann differentiation. Few MPNSTs with perineurial differentiation are also named malignant perineuriomas. Benign perineurioms were classified as intraneural, extraneural (soft tissue), sclerosing, and reticular variant. Histopathological features of intraneural perineurioma are individual nerve axons surrounded by whorls of spindle-shaped cells arranged in an onion bulb-like pattern. However, intraneural malignant perineurioma is uncommon, its characteristic histological features were not clearly described yet. Positive for epithelial membrane antigen (EMA), glut-1 and claudin-1, is characteristic of malignant perineurioma. Herein, we report an intraneural malignant perineurioma in median nerve of a 13-year-old girl. The clinicopathological features were summarized and the related literatures were reviewed. PMID- 25120843 TI - Membranous basal cell adenoma arising in the eyelid. AB - Basal cell adenoma (BCA) is a specific entity that lacks the myxochondroid stromal component of pleomorphic adenoma. Membranous basal cell adenoma is a rare variant of BCA, which is characteristic by abundant eosinophilicextracellular hyaline material deposited either inside or at the periphery of the epithelial islands. Herin we describe the first case of membranous BCA arising in the upper eyelid in a 38-year-old woman. A well-demarcated nodule arising in the eyelid was composed of isomorphic basaloid cells organized with a prominent basal cell layer and distinct basement membrane-like material. Immunohistochemically, S100 protein and p63 highlighted the basal aspect of the peripheral epithelial cells, while CK7 expressed on the luminal cells. A diagnosis of membranous basal cell adenoma of the eyelid was made. At follow-up for 2 years and 3 months later, there was no evidence of recurrence. Further pathological characteristics of this disease are discussed. PMID- 25120844 TI - Basal cell adenoma in the parotid: a bizarre myoepithelial-derived stroma rich variant. AB - Basal cell adenoma (BCA) is a specific entity that lacks the myxochondroid stromal component of a pleomorphic adenoma. There are six histopathological types of BCA: solid, tubular, trabecular, membranous, cribriform, and myoepithelial derived stroma rich. Myoepithelial-derived stroma rich variant is so rare, especially with cellular atypia. Herin we describe a rare case of BCA arising in the parotid on a 25-year-old man. A well-demarcated nodule arising in the parotid that was composed of basaloid cells, forming small duct-like or tubular structures containing basement membrane-like material, as well as highly cellular elongated cells with hyperchromatic, enlarged, pleomorphic, and bizarre nuclei. Immunohistochemically, S100 protein and p63 highlighted the basal aspect of the peripheral epithelial cells and peripheral spindle and bizarre cells, while CK7 expressed on the luminal cells. We made a diagnosis of "basal cell adenoma, myoepithelial-derived stroma rich variant, with bizarre myoepithelial proliferation". The differential diagnosis includes cellular pleomorphic adenoma, basal cell adenocarcinoma, and carcinoma ex pleomorphic adenoma. After follow-up for 3 years, there was no evidence of recurrence. Further pathological characteristics of this disease are discussed. PMID- 25120845 TI - Nasopharyngeal adenoid cystic carcinoma: a case report and review of the literature. AB - ACC derived from nasopharyngeal epithelial cells is rare, usually benign. In this article, we reported a nasopharyngeal adenoid cystic carcinoma (NACC) in a 31 year-old woman with a symptom of hoarseness, headache, epistaxis slightly, diplopia, facial numbness and dysphagia near 3 months. A tumor on the right side of the nasopharynx was confirmed by laryngoscope check and MRI of the skull base. Histopathological findings showed that tumor cells were arranged in cord-like or acinar-like by atypical hyperplastic epithelial cells forming a cribriform and tubular pattern, and immunohistochemical findings showed that tumor tissues were immunopositive for p63 (+), CK7 (+), CK19 (+), CK8 (+), CK18 (+), SMA (+), CK (+), p53 (++), S-100 (+) and Ki-67 (5%+), and negative for CD34 (-), CK5/6 (-), CEA (-) and CD117 (-). Patient was treated by surgical operation and radiotherapy, and was followed-up near 10 months, no local recurrence and distant metastasis. PMID- 25120846 TI - Successful treatment of recurrent Kimura's disease with radiotherapy: a case report. AB - Kimura's disease is a rare, chronic inflammatory disorder affecting the skin and subcutaneous tissue, predominantly in the head and neck region. It is benign but may be recurrent and difficult to eradicate. A case of recurrent Kimura disease in a 53-year-old man was reported. Radiation therapy was performed for recurrence after surgical excision twice. The prescribed radiation dose was 36 Gy. With a follow-up time of 68 months, the patient was free of the disease. PMID- 25120847 TI - Meningitis and pneumococcal pyomyositis in a child with intramuscular hemangiomas: an autopsy case report. AB - Pyomyositis is the bacterial infection of skeletal muscle, usually accompanied by abscesses. The main etiologic agent is Staphylococcus aureus. There are rare cases attributed to Streptococcus pneumoniae. This paper presents an autopsy of a four year old child with multiple congenital intramuscular hemangiomas that developed pneumococcal pyomyositis associated with meningitis. The authors propose the hypothesis that patients with hemangiomas, mainly the intramuscular type, may also represent a risk group for pyomyositis. The possibility of respiratory/meningeal co-infection, might also be considered even if the clinical picture is restricted to the muscular system. PMID- 25120848 TI - Incidental finding of a giant asymptomatic right atrial tumor. AB - Primary cardiac tumors are very rare, atrial myxoma being the most common benign tumor of the heart. They may present with a great variety of incidental asymptomatic masses to severe life-threatening cardiovascular complications necessitating emergency surgery. Here we report the diagnostic evaluation and successful surgical resection of such a giant cardiac tumor which was found on a routine medical check-up in a 62-year-old patient. Histology confirmed diagnosis of unusually huge myxoma. This article demonstrates it's necessary to include cardiac tumors in the differential diagnosis of subtle and non-specific cardiothoracic symptoms. PMID- 25120849 TI - Expression of Gli1 and Wnt2B correlates with progression and clinical outcome of pancreatic cancer. AB - OBJECTIVE: The aim of this study was to investigate the expression and clinical significance of Gli1 and Wnt2B in pancreatic cancer. METHODS: We have constructed a formalin-fixed paraffin embedded pancreatic tissue microarrays 180 cylindrical tissue cores of human pancreatic cancer and its paracancerous nonmalignant pancreatic specimens (NMPs) from 90 patients. Levels of Gli1 and Wnt2B were measured by immunohistochemistry. We analyzed the correlations between the expression of these factors and clinicopathological parameters including prognosis. RESULTS: The expressions of both Gli1 and Wnt2B in human pancreatic cancer tissues were significantly higher than those of normal pancreatic tissues (P=0.000, P=0.004 respectively). The analysis showed that the high cytoplasmic expression levels of Gli1 in pancreatic cancer tissues had significant correlation with lymph node metastasis (P=0.036) and Wnt2B had significant correlation with perineural invasion (P=0.045). Gli1 and Wnt2B have no positive correlation. Survival analysis by Kaplan-Meier demonstrated that elevated Wnt2B expression in cancer tissue predicted worse overall survival (OS) compared with group in lower expression (P=0.024). No correlation was found between the expression of Gli1 and overall survival of pancreatic cancer patients (P>0.05). CONCLUSIONS: In conclusion, these results indicate that the high-expression levels of Gli1 and Wnt2B might play a pivotal role during tumorigenesis of pancreatic cancer, and the high expression of Wnt2B might be associated with poor prognosis. PMID- 25120850 TI - Immunohistochemical expression of MPO, CD163 and VEGF in inflammatory cells in acute respiratory distress syndrome: a case report. AB - Acute respiratory distress syndrome (ARDS) is a serious medical condition occurring in patients with polytrauma, pulmonary or non-pulmonary sepsis, pneumonia and many other circumstances. It causes inflammation of the lung parenchyma leading to impaired gas exchange with a systemic release of inflammatory mediators, causing consequential lung tissue injury, hypoxemia and frequently multiple organ failure. The aim of current study was to describe expression of inflammatory markers (myeloperoxidase, CD163 and vascular endothelial growth factor) by the cells in acute phase of ARDS. The lung samples of a 20-year-old man who had suffered a serious motorbike accident were obtained for histological examination. He died on the seventh day as a consequence of respiratory failure. Our results imply that expression of CD163 was restricted to activated alveolar macrophages and monocytes. Immunopositivityof MPO was observed in neutrophil granulocytes within lung alveoli and lung blood vessels. Myeloperoxidase positivity was observed in alveolar macrophages, too. Vascular endothelial growth factor was expressed in cytoplasm of neutrophil granulocytes, monocytes, small-sized alveolar macrophages and type II pneumocytes localized mostly inside lung alveoli. On the contrary, no positivity was observed in lung endothelial cells of blood vessels. PMID- 25120851 TI - Clinicopathological and prognostic significance of microRNA-107 in human non small cell lung cancer. AB - BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs which can function as oncogenes or tumor suppressor genes in human cancers. Researchers have found that the expression level of miR-107 was decreased in human non-small cell lung cancer (NSCLC) tissues and cell lines, however, its clinicopathological and prognostic significance in NSCLC has not been investigated. METHODS: Quantitative real-time PCR (qRT-PCR) was used to analyze the expression of miR-107 in 137 pairs of fresh NSCLC and matched adjacent normal tissue specimens. The chi-square test and Fishers exact tests were used to examine the associations between miR-107 expression and the clinicopathological characters. The overall survival (OS) and progression-free survival (PFS) were analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. RESULTS: The expression level of miR-107 was significantly lower in tumor tissues than that in corresponding noncancerous tissues (0.4676 +/- 0.2078 vs. 1.000 +/- 0.3953, P<0.001). Low expression of miR-107 was found to significantly correlate with TNM stage (p=0.001), regional lymph node involvement (p=0.04), and tumor differentiation (p=0.003). Kaplan-Meier analysis with the log-rank test indicated that low miR 107 expression had a significant impact on OS (35.2% vs. 69.3%; P=0.008) and PFS (30.0% vs. 56.2%; P=0.029). In a multivariate Cox model, we found that miR-107 expression was an independent poor prognostic factor for both 5-year OS (HR=2.57, 95% CI: 1.88-10.28; P=0.007) and 5-year PFS (HR=3.08, 95% CI: 2.01-8.92; P=0.003). CONCLUSION: The expression of miR-107 was decreased in NSCLC. Low expression of miR-107 was significantly associated with tumor progression and decreased survival in patients with NSCLC, indicating that miR-107 may serve as a novel prognostic marker in NSCLC. PMID- 25120853 TI - [Factors associated with infection in rheumatoid arthritis]. PMID- 25120852 TI - Inosine triphosphate pyrophosphohydrolase (ITPA) polymorphic sequence variants in Chinese ALL children and possible association with mercaptopurine related toxicity. AB - Genetic polymorphisms are important factors in effects and toxicity of chemotherapeutics. This study aimed to investigate whether there was a correlation between genotype or haplotype of inosine triphosph pyrophosphohydrolase(ITPA) and toxicities during maintenance therapy with mercaptopurine (6-MP) in Chinese patients with acute lymphoblastic leukemia (ALL). 95 ALL children who hospitalized between October 2004 and September 2007,were retrospectively analyzed. 6-MP toxicity was documented according to Common Toxicity Criteria, Version 2.0. ITPA sequencing was undertaken. Correlation between genotype/haplotype and 6-MP toxicity was analyzed. The results indicated that 50 cases (52.6%) had grade III-IV of bone marrow inhibition. These children had long-term disease-free survival (DFS), without hepatic and other organs' dysfunction and secondary tumors. Three variations were observed in ITPA exon 2 (94 C -> A), exon 3 (138 G -> A), and exon 8 (561 G -> A), the 94A carriers (CA and AA) had a lower risk of developing 6-MP toxicity when compared with carriers of the CC genotype (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.12-0.98, P = 0.039). The risk of 6-MP intolerance was decreased in patients with 138 allele and 561 allele polymorphism, but with no significant difference. Patients carrying the haplotype 94A-138A-561A was tolerance compared to those with wild-type haplotype 94C-138G-561G (OR: 0.26, 95% CI 0.07-0.94 P = 0.043). In conclusion, the risk of 6-MP intolerance was decreased in patients with 138 allele and 561 allele polymorphism, but without significant difference. Patients carrying the haplotype 94A-138A-561A was tolerance compared to those with the wild-type haplotype 94C-138G-561G. PMID- 25120854 TI - [Epidemiology and management of intrapartum infections in the maternity ward of Oueme-Plateau county hospital in Benin]. PMID- 25120855 TI - Providing medical care in unfamiliar settings; experience of an Egyptian campaign in Uganda. AB - Medical service in many African countries is affected by the limited infrastructure and the lack of economic and human potentials. Uganda is one the countries that suffers from lack of physicians as well as shortage of many medical facilities with many endemic health problems such as Goiter. A surgical camp was done by an Egyptian team of 8 physicians; three general surgeons, one pediatric surgeon, two gynecologists and one anesthetist. Over two hundred cases were screened in the outpatient clinic. Eighty nine operations were done in four days. General surgery procedures were 45 operations (50%), Pediatric procedures were 23 operations (26%) and Gynecological operations were 21 operations (24%) In conclusion Humanitarian relief for poor population in the developing world countries needs vigilant international collaboration. Special attention should be given to goiter in African countries. Training doctors from sub-Saharan African nations should be on the top of the agenda of the international medical community in order to reach a definitive solution for their health problems. PMID- 25120856 TI - Giant brain tuberculoma mimicking a malignant tumor in a child. PMID- 25120857 TI - Fracture of the bamboo spine (chronic ankylosing spondylitis) after cervical injury. PMID- 25120858 TI - [Eyelid S-shape deformation revealing a pleomorphic adenoma]. PMID- 25120859 TI - Effect of body composition on bone mineral density in Moroccan patients with juvenile idiopathic arthritis. AB - INTRODUCTION: The link between bone mass and body composition is widely recognized, but only few works were selectively performed on subjects with juvenile idiopathic arthritis. The aim of our study was to investigate the effect of body composition on bone mineral density (BMD) in Moroccan patients with juvenile idiopathic arthritis. METHODS: Thirty three children with juvenile idiopathic arthritis (JIA) were included in a cross-sectional study. The diagnosis of JIA was made according to the criteria of the International League of Association of Rheumatology (ILAR). Body mass index (BMI) was calculated from the ratio of weight/height(2)(kg/m(2)). Pubertal status was determined according to the Tanner criteria. Bone status, body composition and bone mineral content (BMC) were analyzed by using dual-energy X-ray absorptiometry (DXA). BMD was assessed at the lumbar spine (L1-L4) and at total body in (g/cm(2)). Total body fat tissue mass (FTM) and lean tissue mass (LTM) were also analyzed by DXA and expressed in kilograms. In children, low BMD was defined as a Z-score less than 2 and osteoporosis was defined as a Z-score less than -2 with a fracture history. RESULTS: A cross-sectional study was conducted in 33 Moroccan patients with JIA aged between 4 and 16 years, Fat mass was not related to bone density; in contrast, BMD was positively associated to LTM in total body(r = =0.41, p= 0.04) but not in lumbar spine (r = 0.29, p= 0.17). There exist significant correlation between BMC and BMD in total body (r = 0.51, p = 0.01). CONCLUSION: This study suggests that the LTM is a determining factor of the BMD during adolescence. Other studies with a broader sample would be useful to confirm this relation. PMID- 25120860 TI - Pattern of cardiovascular admissions at Nnamdi Azikiwe University Teaching Hospital Nnewi, South East Nigeria. AB - INTRODUCTION: Cardiovascular disease (CVD) is one of the top killer diseases in the world sparing neither developed or developing countries. The study was carried out to determine the pattern of cardiovascular admissions at Nnamdi Azikiwe University Teaching Hospital Nnewi South East Nigeria. METHODS: The study was a retrospective study covering the period January 2007 to December 2009. SPSS version 13 software was used to analyze data. RESULTS: 537 (15%) patients were admitted into the study out of 3546 patients {females 1756 and 1790} admitted into medical wards. 322 (60%) of study population were males and 215 (40%) females. 359(67.5%) were discharged, 170 (32%) died and 8 (0.5%) were discharged against medical advice. The majority of the deaths 105(61.8%), were in patients with CVA. Most of the deaths (111 or 65.3%) occurred within the first seven days of admission. The mean age of the population was 60.7 years +/-15.9 with a range of 18 to 110 years. The length of stay in hospital ranged between 1 and 140 days with a mean of 13.5 +/- 13.9 days and a median of 10 days. 33 of the subjects were single, 406 were married, 94 were widowed (11 males and 83 females) and 4 were divorced. 46.7% (251) were admitted for CVA and 30.9% (166) for heart failure. Cardiomyopathy/valvular heart diseases (clinical diagnosis due to absence of echocardiography) constituted 3.9%, hypertension 20.5% and pre existing hypertension with uremia 1.9%. CONCLUSION: The study has shown that cardiovascular disease contributed significantly to medical admissions the elderly accounting for a significant proportion. There is thus the need for intensification of primary preventive strategies for cardiovascular diseases. PMID- 25120861 TI - [Epidemiological profile of primary malignant tumors of the salivary glands: about 154 cases]. PMID- 25120862 TI - [Esophageal involvement during pemphigus vulgaris]. PMID- 25120863 TI - [Rectal stromal tumor: report of a case]. PMID- 25120864 TI - Painless extensive ossification of the Achilles tendon: a diagnostic trap? PMID- 25120865 TI - [Occipital tumors: a medical or surgical emergency?]. PMID- 25120867 TI - [Pre-renal mass of adrenal origin: what is your diagnosis?]. PMID- 25120866 TI - First results of hormone receptors' status in Malagasy women with invasive breast cancer. AB - INTRODUCTION: Breast cancer is the most common malignancy tumor amongst Malagasy women registered at the pathology unit of the "Institut Pasteur de Madagascar". In Madagascar, there is no laboratory practicing hormone receptors' status on these tumors. Until now no study about hormone receptors' status of Malagasy women with invasive breast cancer was performed. So it will be the first study talking about this topic. The aim of this study was to determine hormone receptors' status in Malagasy women with invasive breast cancer. METHODS: This retrospective and descriptive study was based on patients' medical files from 2009 to 2011. It included all invasive breast cancer diagnosed in Malagasy women at the pathology laboratory located at the "Institut Pasteur de Madagascar", in Antananarivo. Along this period this laboratory has sent paraffin blocks of invasive breast carcinoma in two pathological laboratories in France. RESULTS: We collected 77 cases of invasive breast cancer along this period. The mean age was 48.8 +/- 10.7, ranging from 26 years to 70 years. There were 46.8 % (n = 36) women with progesterone receptor positive (PR+), 53.2 % (n = 41) with progesterone receptor negative (PR-). For the estrogen receptor, 61.0 % (n = 47) were positive and 36.4 % (n = 28) were negative. ER+/PR+ represented 44.2 % (n = 34); ER-/PR- 33.8 % (n = 26); ER +/ PR- 16.8 % (n = 13); ER-/PR+ and ER-/PR- represented respectively 2.6 % (n = 2). CONCLUSION: Patients in our study had more important rate of ER-, PR- and a less important rate of ER+/PR+, PR+. These results suggest that more study related to Hormone Receptor profile should be conducted in Malagasy women with breast cancer. PMID- 25120869 TI - [Heart with six cavities in a 11-year old child]. PMID- 25120868 TI - Tobacco control research in Kenya: the existing body of knowledge. AB - This review examines the existing tobacco control research done in the country. It further identifies key gaps present in research and gives recommendations on priority research areas required to implement effective tobacco control programmes. Published literature, technical reports and reports by the Ministry of Health were reviewed. It included studies that measure tobacco use and its effects, monitor progress of tobacco control, or articles that are discussing tobacco control policy. The review was conducted in January 2013 and included 18 papers. There are six studies that assessed the prevalence of current tobacco consumption which yielded prevalence's of between 3.8%-19%. Only one study tried to determine an association between Tobacco use and Health. Studies that monitored progress of legislation indicated that the country lacked coordinated efforts for tobacco control, enforcement was weak and monitoring of the existing tobacco legislation was poor. This review has demonstrated that Kenya has made efforts to generate knowledge on tobacco control through research. However there is lack of research that demonstrates the effects of tobacco consumption on health and studies that detail the impact of the various tobacco control interventions. PMID- 25120870 TI - A tuberculosis case mimicking lymphoma. AB - Tuberculosis remains a worldwide health problem causing morbidity and mortality. Abdominal tuberculosis is a rare form of the disease. Abdominal form of tuberculosis can mimic other non-infectious diseases. In this report, we presented an abdominal tuberculosis presenting with an intra-abdominal mass lesion and multiple lymphadenopathies that mimics lymphoma. PMID- 25120871 TI - Late onset epilepsy associated with marijuana abuse: a case report with MRI findings. AB - Marijuana is the most widely used illicit substance in the world. The relation between marijuana use and epileptic seizures is still controversial. We report a case of late onset epilepsy associated with marijuana abuse, with brain magnetic resonance imaging (MRI) findings. A 44-year-old patient was admitted for 03 isolated episodes of secondary generalized tonic-clonic seizures. He had a history of 26 years regular marijuana smoking. On admission, we found a tachycardia, psychomotor slowing, asymmetric hyperreflexia, bilateral Babinski sign without weakness. Laboratory work-up showed a high level of urine of Delta-9 tetrahydroxycannabinol. Electroencephalogram was normal. Brain MRI revealed abnormal signal intensities in the right frontal lobe and basal ganglia. Seizures cessation was obtained with anti-epileptic treatment. We suggest that marijuana abuse through vascular and toxic mechanisms could explain seizures in this case. PMID- 25120872 TI - [Colobomatous cyst of the orbit]. PMID- 25120873 TI - [Critical study of the treatment of 159 elderly in psychiatric consultation]. PMID- 25120874 TI - Family and socioeconomic risk factors for undernutrition among children aged 6 to 23 Months in Ibadan, Nigeria. AB - INTRODUCTION: Child undernutrition is a major public health problem in Nigeria and other Sub-Saharan African countries. However, few analytical studies have quantified the role of risk factors. This study was conducted to determine the socio-economic and family related risk factors for undernutrition among children in Ibadan, Nigeria. METHODS: A case-control study was conducted among children 100 cases and 200 controls aged 6-23 months. A semi-structured interviewer- administered questionnaire was used to obtain information on socio-economic status, infant feeding practices of the mothers, children's immunization status and recent episodes of common childhood illnesses. Bivariate and multivariate analyses were conducted to identify the risk factors. RESULTS: On bivariate analysis, the maternal factors associated with undernutrition were maternal level of education below secondary level, monthly income below $20 and polygamous marriage. Socio-economic factors significantly associated with malnutrition were residence in a high density area, family accommodation in a single room apartment and family weekly expenditure on food below $55. Children's characteristics associated with child malnutrition included incomplete immunization for age, recent episodes of diarrhoea and acute respiratory infection. The significant risk factors on multivariate analysis were maternal monthly income <$20, monthly household food expenditure <$55, residence in a one room apartment, higher birth order and incomplete immunization of the child. CONCLUSION: The multiplicity of risk factors identified is indicative of the need for a multidisciplinary approach in developing preventive strategies child undernutrition. PMID- 25120875 TI - [Sirenomelia (Mermaid syndrome): description of the first Congolese cases and review of the literature]. PMID- 25120876 TI - [Cholesteatoma of the middle ear - retrospective study about 145 cases]. PMID- 25120877 TI - [Esophagitis dissecans: a rare cause of dysphagia]. PMID- 25120878 TI - [Gouty tophi of the hand revealing a gout]. PMID- 25120879 TI - [Tuberculous tenosynovitis of the extensors of the hand: a rare localization of tuberculosis]. PMID- 25120880 TI - [Ophthalmic zoster of th eyelid: good outcome with valaciclovir]. PMID- 25120881 TI - Forestier's disease presenting with dysphagia and disphonia. AB - Forestier's disease, also known as diffuse idiopathic skeletal hyperostosis (DISH), is a pathology of vertebral bodies characterised by exuberant osteophytis formation. Forestier's disease is usually managed conservatively. Surgical resection of the osteophytes is reported to be an effective treatment for severe cases and/ or cases with airway obstruction. We report a 55-year-old man presenting with 6 months' progressive dysphagia and dysphonia. He was managed successfully with an anterior cervical osteophytectomy without fusion. A literature review is included. PMID- 25120882 TI - Unusual presentation of hepatocellular carcinoma invading the anterior abdominal wall muscles. AB - Hepatocellular carcinoma (HCC) is a common cancer all over the world. It demonstrates a tendency for vascular invasion, producing extensive intrahepatic metastases and portal vein or inferior vena cava extension. Tumor spread of abdominal diseases via hepatic ligaments has also been reported. The author reports a rare case of HCC invading the anterior abdominal wall muscles and protruding into the subcutaneous fat. PMID- 25120883 TI - Intramuscular lipoma: infiltrating vs. well-circumscribed variant. PMID- 25120884 TI - [Contribution of imaging in the diagnosis of infectious sacroiliitis: about 19 cases]. PMID- 25120885 TI - [Bladder exstrophy: about a case diagnosed tardily]. PMID- 25120887 TI - Effects of disadvantage in early life on cardiometabolic health status in adulthood. PMID- 25120886 TI - Effects of Nrf2 deficiency on bone microarchitecture in an experimental model of osteoporosis. AB - OBJECTIVE: Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2), an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis. METHODS: Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2(-/-)). Bone microarchitecture was analyzed by MUCT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123. RESULTS: Sham-operated or ovariectomized Nrf2(-/-) mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2(-/-) mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro. CONCLUSION: We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture. PMID- 25120888 TI - Binge drinking and its relation to metabolic syndrome in korean adult men. AB - BACKGROUND: It is reported that heavy drinking increases the risk of metabolic syndrome. But there have been few studies on the relationship between the intensity of drinking and metabolic syndrome when drinking the same amount of alcohol. This study aimed to assess the relationship between the frequency of binge drinking and metabolic syndrome in Korean adult men. METHODS: From the database of the 4th and 5th Korea National Health and Nutrition Examination Survey conducted in 2007-2010, data of 8,305 adult men (>=19 years of age) was included in this analysis. Cross-sectional relationship between the frequency of binge drinking and metabolic syndrome was investigated adjusting for pure alcohol consumed per day. RESULTS: Adjusting for various confounders including pure alcohol consumed per day, the adjusted odds ratio for metabolic syndrome in those in higher frequency (more than 1/wk) binge drinking group was 1.62 (95% confidence interval, 1.30 to 2.03; P for trend = <0.001) compared to those in the non-binge drinking group. Through analysis of the relationship between pure alcohol consumed per day and metabolic syndrome, it was found that pure alcohol consumed per day had a positive relation to metabolic syndrome in the higher frequency binge drinking group (P for trend = 0.041). The relationship was inverse in the non-binge drinking group (P for trend = 0.002). CONCLUSION: Our study found a positive relationship between frequency of binge drinking and metabolic syndrome in adult men. And the effect of drinking on metabolic syndrome may depend on the frequency of binge drinking. Further studies are required to confirm this association. PMID- 25120889 TI - Association between Appendicular Fat Mass and Metabolic Risk Factors. AB - BACKGROUND: Different regional fat depots have different effects on lipid and glucose metabolism. The purpose of this study is to examine the relationship between body fat distribution as measured by dual-energy X-ray absorptiometry (DEXA) and metabolic risk factors and to disclose whether there is any difference between groups with and without metabolic syndrome (MS). METHODS: A total of 292 participants (98 men, 194 women) over 19 years old underwent whole-body DEXA to evaluate body composition with respect to the whole body, leg, arm, and android regions. Anthropometry and blood tests for metabolic risks were measured. RESULTS: One hundred and seven participants were diagnosed with MS. The MS group had significantly higher android fat (%) and had lower leg fat (%), arm fat (%), and appendicular (arms + legs) fat (%) than the non-MS group. Android fat (%) had a positive correlation with waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, log insulin, hemoglobin A1c (HbA1c), triglyceride (TG), and low density lipoprotein cholesterol, and had a negative correlation with high density lipoprotein (HDL) cholesterol. Appendicular fat (%) had a negative correlation with WC, SBP, DBP, glucose, log insulin, HbA1c, and TG, and had a positive correlation with HDL cholesterol. The association of appendicular fat with metabolic risk was consistently observed in non-MS, but the association was not observed except for SBP, glucose and log insulin in MS. CONCLUSION: In contrast with the adverse effects of android fat, appendicular fat distribution was associated with decreased risks of MS. The protective effect of appendicular fat against metabolic risk factors in non-MS was less characteristic in MS. PMID- 25120891 TI - Pro Re Nata Prescription and Perception Difference between Doctors and Nurses. AB - BACKGROUND: Pro re nata (PRN) prescription is a frequently used prescription method in hospitals. This study was conducted to investigate actual condition of PRN prescription and whether administration error occurred because of perception difference between doctors and nurses. METHODS: From May to July 2012, a survey was conducted among 746 doctors and nurses (88 doctors and 658 nurses) working at 5 hospitals located in Seoul, Gyeong-gi, and Gangwon Province. Doctors generating PRN prescription responded to actual conditions of PRN prescription and both doctors and nurses reported whether administration error occurred due to perception difference. RESULTS: Average number of PRN prescription of surgical residents was 4.6 +/- 5.4, which was larger than that of medical residents (1.7 +/- 1.0). Surgical residents more frequently recorded maximum number of daily intake (P = 0.034) and, although not statistically significant, more often wrote exact single dosage (P = 0.053) and maximum dosage per day (P = 0.333) than medical residents. Doctors expected nurses to notify them before the administration of medication; however, nurses were more likely to conduct PRN administration by their own decision without informing doctors. In addition, some doctors and nurses experienced administration errors because of it. CONCLUSION: Standard prescription methods need to be established since there is a perception difference in PRN prescription between doctors and nurses and this could be related to administration errors. PMID- 25120890 TI - Association between Nutrition Label Reading and Nutrient Intake in Korean Adults: Korea National Health and Nutritional Examination Survey, 2007-2009 (KNHANES IV). AB - BACKGROUND: Nutrition labels provide various information on the nutrient contents of food. However, despite the recent increase in the interest in dietary intake and expansion of related policies, studies on the association between nutrition label reading and dietary intake are lacking in Korea. METHODS: This study analyzed the 2007-2009 KNHANES (Korean National Health and Nutrition Examination Survey) data. To examine macronutrients and micronutrients intake according to nutrition label reading, analysis of covariance was used. Multiple logistic regression analysis was also used to examine the association between adherence to dietary reference intake and nutrition label reading. RESULTS: Nutrition label reading was significantly high among women, youth, and those with high education and high household income. Nutrition label reading was associated with higher intake of calcium and vitamin C in men and the lower intake of calorie, carbohydrates and higher energy ratio of protein in women. Additionally, male nutrition label readers were associated with adherence to dietary reference intake of fiber (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.23 to 3.26) and calcium (OR, 1.26; 95% CI, 1.03 to 1.54). In women, there were no significant differences in the adherence to the dietary reference intake in fat, fiber, sodium, potassium, and calcium according to the nutrition label reading. CONCLUSION: In men, nutrition label reading was associated with healthier intake of several micronutrients, although this was not observed in women. Consideration for clearly reporting vulnerable micronutrients in nutrition labels is necessary. PMID- 25120892 TI - The Relationship between Metabolic Syndrome and Childhood Maternal Education Level, Job Status Findings from the Korean National Health and Nutrition Examination, 2007-2009. AB - BACKGROUND: Childhood socioeconomic status (SES) is known to affect cardio metabolic disease risk. However, the relationship between childhood SES and metabolic syndrome (MetS) remains uncertain. Therefore, we investigated the relationship between childhood SES, as measured by maternal education and occupational status and adult-onset MetS in the Korean population. METHODS: We examined the association between childhood SES, as measured by maternal education level and occupational status during an individual's childhood, and MetS in Korean adults aged 20 to 79 years who participated in the 2007-2009 Korean National Health Examination and Nutrition Survey. The components of MetS, including waist circumference, fasting glucose, lipid profiles, and blood pressure, were measured. Adjusted odds ratios (ORs) for MetS were calculated using multiple logistic regression models. RESULTS: Significant differences in the association between maternal education level, occupational status, and MetS were found between males and females. In females, the adjusted MetS OR for the highest maternal education quartile relative to the lowest quartile was 0.46 (0.21-0.99). Similarly, in females, the adjusted OR for individuals whose mothers worked when they were children relative to those whose mothers did not work was 1.23 (1.04-1.44). In males, no significant associations between maternal education, maternal occupational status, and MetS were found. CONCLUSION: We found independent, positive associations between maternal education and occupational status and MetS in Korean females. These findings suggest that public health education targeting MetS prevention should be considered, especially among children with less opportunity for maternal support. PMID- 25120893 TI - Gluten-free diet and quality of life in celiac disease. AB - Many recent studies overshadow the effects of gluten-free diet. Gluten-free diet positive effects were observed in celiac disease patients: increase in body mass index, higher energy intakes, reducing adiposity gain, moderates the risk of the associated complications. However, adhering to a gluten-free diet is difficult for many people. A new solution is needed for quality of life of celiac disease patients, not for celiac disease treatment. Health education on gluten-free diet at home and in society seems to be the solution. The aim of our study is to evaluate the recent research on gluten-free diet as a nutritional therapy for patients with celiac disease. To achieve this purpose we have analyzed the published studies from 2008 to the present on nutrition in celiac disease. PMID- 25120894 TI - Prevalence of hepatitis D virus in hepatitis B virus infected patients referred to Taleghani hospital, Tehran, Iran. AB - AIM: The aim of this study was to determine the prevalence of HDV infection between HBV chronic patients referred to gastroenterology ward of Taleghani hospital Tehran, Iran and also investigating the risk factors in acquiring the HDV infection. BACKGROUND: Hepatitis B virus (HBV) and Hepatitis D virus (HDV) are major public health issues. Worldwide there are approximately 350 million individuals chronically infected with the HBV. A significant part of them, including 15 to 20 million coinfected with HDV. Hepatitis Delta virus is transferred mostly through blood and body fluids. PATIENTS AND METHODS: HBV and HDV infections were evaluated by Enzyme-linked immunosorbent assay (ELISA). Liver functional tests were assessed through auto analyzer. Patients were interviewed and data along the test results were entered into SPSS program. We used chi square, independent t-test and logistic regression for statistical analysis. RESULTS: 278 (54.6%) patients of the study group were male and 231 (45.4%) were female and the mean age of patients was 40.03 +/- 14.93. From 509 patients, 39(7.7%) had anti-HDV antibody. In a uni-variable analysis, age (p=0.001), periodontal procedures (p=0.015), endoscopy (p=0.024) and colonoscopy (p=0.012) were significantly related to HDV seropositivity. After adjustment by logistic regression, age remained the only significant factor in acquiring HDV infection. CONCLUSION: We highly recommend the health care workers to strictly follow the disinfection protocols of medical instruments. Since HDV seroprevalence changes over time, regular epidemiological studies are necessary to monitor the epidemiological trend of infection. PMID- 25120895 TI - Comparison of half-dose and full-dose triple therapy regimens for Helicobacter pylori eradication in patients with end-stage renal disease. AB - AIM: The aim of this study was to compare the half-dose and full-dose triple therapy regimens for Helicobacter pylori (Hp) eradication in patients with end stage renal disease. BACKGROUND: H. Pylori is one the most important causes of dyspepsia in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS: Sixty-six patients with ESRD were enrolled in the study with Hp infection and peptic disease with a need of Hp eradication. Patients were randomly assigned to full-dose (A=35 patients) or half-dose group (B=31 patients). Patients received clarithromycin 500 mg, amoxicillin 1000 mg and omeprazole 20 mg twice daily in group A and clarithromycin 250 mg and amoxicillin 500 mg twice daily and omeprazole 20 mg once daily in group B for two weeks. Patients provided stool samples 4 weeks of completing study to assess the success of Hp eradication by Hp specific stool antigen. Finally, the rate of eradication and complications were compared between two groups. RESULTS: The successful Hp eradication was achieved in 26 patients (74%) in group A and in 22 patients (74%) in group B. The difference between 2 groups was not statistically significant (p=0.973) (per protocol analysis). CONCLUSION: Half-dose triple-therapy with clarithromycin, amoxicillin and omeprazole is as effective as full-dose triple-therapy to eradicate the Hp in patients with ESRD. According to lower toxicity level, complications and cost in half-dose regimen in this subset of patients, this protocol is advised. PMID- 25120896 TI - The efficacy of a synbiotic containing Bacillus Coagulans in treatment of irritable bowel syndrome: a randomized placebo-controlled trial. AB - AIM: We aimed to evaluate the efficacy of a synbiotic containing Bacillus Coagulans in treatment of IBS. BACKGROUND: Some studies have shown the efficacy of probiotics in the treatment of irritable bowel syndrome (IBS). PATIENTS AND METHODS: Adult IBS patients (n=85) were randomized to receive a synbiotic containing Bacillus Coagulans or placebo for 12 weeks. Frequency of IBS symptoms including abdominal pain (scored 1 to 7), and diarrhea and constipation (scored 1 to 5) was evaluated before and after the intervention and then after nine months follow-up. RESULTS: Twenty-three patients in the synbiotic group and 33 patients in the placebo group completed the study (age = 39.8+/-12.7 years, 78.6% female). After treatment, more reduction in abdominal pain frequency was observed with synbiotic compared with placebo (score reduction 4.2+/-1.8 vs. 1.9+/-1.5, P<0.001). Diarrhea frequency was decreased in the synbiotic group, but not in the placebo group (score reduction 1.9+/-1.2 vs. 0.0+/-0.5, P<0.001). Decrease in constipation frequency was the same between the two groups (score reduction 0.9+/ 1.2 vs. 0.8+/-1.1, P=0.561). After nine months follow-up, abdominal pain frequency was decreased (P=0.016), constipation frequency was increased (P<0.001), and diarrhea frequency remained unchanged in the synbiotic group (P=1.000). In the placebo group, abdominal pain frequency was increased (P<0.001), constipation frequency remained unchanged (P=0.553), and diarrhea frequency was increased (P<0.001). CONCLUSION: Bacillus Coagulans improves abdominal pain and diarrhea in IBS patients. Further studies on a larger sample of patients are warranted. PMID- 25120898 TI - Molecular identification of Giardia lamblia; is there any correlation between diarrhea and genotyping in Iranian population? AB - AIM: The aim of this study is to investigate the molecular identification of Giardia lamblia in patients with diarrhea. BACKGROUND: Giardiasis caused by Giardia lamblia is a common intestinal disease. Although this parasitic infection found in mammals including human, pets and livestock, but few species within the genus Giardia can infects humans. G. lamblia have seven complex genotypes termed (A-H). Genotype A and B the main causes of human infections. PATIENTS AND METHODS: Sixty seven microscopically positive G. Lamblia samples were collected from clinical laboratories in Isfahan province between June 2013 and February 2014. Extraction of genomic DNA was performed for 65 concentrated cysts and 2 cultured trophozoites. Partial sequences of tpi including 148-bp and 81-bp were amplified for detection the genotypes A and B using RFLP- PCR protocol respectively. RESULTS: PCR results showed that out of 67 patients with giardiasis infection, genotype A (148 bp) was detected in 40 isolates (59.70%) compared to genotype B (81 bp) isolated was detected in 25 isolates (37.31%). Also two isolates (2.98%) had mix infection infected with genotype A and B. By comparing the frequency of genotype A (81.8%) and genotype B (13.6%), we found that genotype A is six times higher prevalence than genotype B in patients with diarrhea. CONCLUSION: We suggest that using sensitive techniques and larger sample for detection of G. lamblia genotypes and their subtypes would be necessary for investigation the immune system respond and correlation with diarrhea in the future studies in Iran. PMID- 25120897 TI - Discrimination of Entamoeba Spp. in children with dysentery. AB - AIM: The present study was performed in order to differentiate E. histolytica and E. dispar in children from Gorgan city, using a PCR method. BACKGROUND: Differential detection of two morphologically indistinguishable protozoan parasites Entamoeba histolytica and E. dispar has a great clinical and epidemiological importance because of potential invasive pathogenic E. histolytica and non-invasive parasite E. dispar. PATIENTS AND METHODS: One hundred and five dysentery samples were collected from children hospitalized in Taleghani hospital in Gorgan city. The fecal specimens were examined by light microscopy (10X then 40X) to distinguish Entamoeba complex. A single round PCR amplifying partial small-subunit rRNA gene was performed on positive microscopy samples to differentiate E. histolytica/ E. dispar and E. moshkovskii from each other. RESULTS: Twenty-five specimens (23.8%) were positive for Enramoeba complex in direct microscopic examination. PCR using positive controls indicated E. histolytica and E. dispar in two (2/25, 8%) and three (3/25, 12%) samples, respectively. CONCLUSION: There is a warrant to performing molecular diagnosis for stool examination at least in hospitalized children in order to prevent incorrect reports from laboratories and consequently mistreating by physicians. PMID- 25120899 TI - Cannabinoid hyperemesis should be recognised as an effect of chronic cannabis abuse. AB - Here we describe the second reported case of cannabinoid hyperemesis in UK. A 42 years old patient presented on more than one occasion with vomiting, abdominal pain, fever and dehydration and treated as sepsis with antibiotics. Extensive investigations including upper GI endoscopy, colonoscopy, chest X-ray, abdominal ultrasound, abdominal CT scan, barium swallow and echocardiogram; all reported normal. Once the diagnosis of cannabinoid hyperemesis was established, he was advised to abstain from cannabis use resulting in complete resolution of his symptoms. PMID- 25120900 TI - Right cervical lymphadenopathy: a rare presentation of metastatic hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the most common, malignant tumor of the liver. Hepatocellular carcinoma (HCC) commonly metastasizes to the lungs, abdominal lymph nodes, adrenal glands, or bones. Distant lymph node metastases are rare in hepatocellular carcinoma. A 49-year-old male patient presented with right sided neck mass. On examination there was right cervical lymphadenopathy and hepatomegaly. Excisional cervical lymph node biopsy showed metastatic carcinoma. However, further examination of the biopsy specimen for immuno-histochemistry markers, shows positivity for HepPar-1 & CD-10 suggestive of hepatocellular carcinoma. Considering the high incidence of HCC in Asia, a special attention should be given to such unusual site of presentation and metastasis of HCC; therefore, not to miss the diagnosis. PMID- 25120901 TI - An unusual cause of upper gastrointestinal bleeding. PMID- 25120902 TI - Recent advances in oesophageal diseases. AB - Dong Y, Qi B, Feng XY, Jiang CM. Meta-analysis of Barrett's esophagus in China. World J Gastroenterol 2013;19(46):8770-8779 The disease pattern of Barrett's esophagus (BE) in China is poorly characterised particularly in comparison with other developed countries. This meta-analysis of 3873 cases of BE collated from 69 clinical studies conducted in 25 provinces between 2000 and 2011 investigated the epidemiology and characteristics of BE in China compared to Western countries. The total endoscopic detection rate of BE was 1.0% (95%CI: 0.1%-1.8%) with an average patient age of 49.07 +/- 5.09 years, lower than many Western countries.The authors postulate this may be attributed to environmental risk factor variation, distinct genetics and different medical practice including diagnostic criteria for BE and expertise in endoscopy. This study identified a 1.781 male predominancefor BE in China, consistent with Western reports. Short segment BE accounted for 80.3% of cases with island type and cardiac type the most common endoscopic (44.8%) and histological (40.0%) manifestations respectively. Of the 1283 BE cases followed up for three to 36 months the incidence of esophageal cancer was 1.418 per 1000 person-years, lower than the incidence reported in Western countries. Lee HS, Jeon SW. Barrett esophagus in Asia: same disease with different pattern. ClinEndosc 2014;47(1):15-22 Barrett's esophagus (BE) is a common, pre-cancerous condition characterised by intestinal metaplasia of squamous esophageal epithelium usually attributed to chronic gastric acid exposure. This review article explores important differences in the disease pattern of BE between Asian and the Western countries. Overall the prevalence of BE is lower in Asia compared to the West with a greater proportion of short-segment type. The authors identify great variability in the endoscopic and pathologic diagnostic criteria for BE. Many of the studies in Asian countries did not use a standardised four-quadrant biopsy protocol which may have led to an underestimation of BE prevalence. The review highlights an increasing incidence of esophageal adenocarcinoma in the West but unclear disease trend in Asia with inter-country variability. Similarly in Asian and Western countries BE is associated with the presence of hiatus hernia, advancing age, male gender, alcohol consumption, smoking, abdominal obesity and longer duration of gastro esophageal reflux disease. The authors postulate that Helicobacter pylori infection, more prevalent in Asia than the West, may have a protective effect on BE. There is a need for larger, prospective studies to further clarify the disease pattern of BE in Asian countries. Clearly standardisation of the diagnostic process for BE is important to validate the differences in disease trends between Asian and Western countries. Kiadaliri AA. Gender and social disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7 Esophageal cancer (EC) is a major cause of morbidity and mortality particuarly in Iran where the incidence rate exceeds the global average. An understanding of the factors influencing the province-specific incidence of EC in Iran is important to inform disease-prevention strategies and address health inequalities. This ecological study used cancer registry data to investigate the relationship between gender and social class and the incidence of EC in Iran at province-level between 2003 and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan in females. Overall the EC incidence did not significantly differ according to gender. Interestingly, during the study period the ASIR increased by 4.6% per year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect increasing rates of establised risk factors for EC including obsesity and gastro esophageal reflux disease alongside more vigilant recording of new cases. Social class was inversely associated with the ASIR of EC regardless of gender which may be attributed to class differences in risk factor distribution particularly smoking, diet and obesity. An appreciation for the limitations of an epidemiological study is important when interpreting results which should be further evaluated in future studies. Islami F et al.Determinants of gastroesophageal reflux disease, including hookah smoking and opium use- A cross sectional analysis of 50,000 individuals. PLoS One 2014;9(2):e89256 Gastroesophageal reflux disease (GERD) is a highly prevalent cause of gastrointestinal symptoms worldwide incurring great cost to the primary and secondary healthcare sectors. An improved understanding of the factors which influence GERD symptoms in low- to medium- income countries may inform public health initiatives. This study analysed prospective data from the Golestan cohort study, primarily established to investigate determinants of upper gastrointestinal cancers, toexplore the risk factors influencing GERD symptoms (regurgitation and/or heartburn) in 50,045 individuals aged 40-75 years in Golestan Province, Iran enrolled between 01/2004 and 06/2008.Of note, 39.12% of individuals denied ever experiencing GERD symptoms. A further 19.89% reported at least once weekly GERD symptoms with 11.83% experiencing daily symptoms. Severe symptoms, defined as disturbing daily work or sleep, were recorded by 11.33% of individuals. Separately the occurrence of daily GERD symptoms and severe symptoms were inversely associated with male gender (OR 0.36, 95% CI 0.33-0.39 both), level of formal education (p=0.01 and p=0.001 respectively), wealth score (p<0.001 both) and regular nass chewing (OR 0.86, 95% CI 0.75-0.98 and OR 0.87, 95% CI 0.76-0.99 respectively)and were positively associated with body mass index (p<0.001 both), intensity of physical activity (p=0.04 both), cigarette pack years (p<0.001 both), alcohol consumption (OR 1.36, 95% CI 1.13-1.64 and OR 1.53, 95% CI 1.28-1.83 respectively) and opium use (OR 1.82, 95% CI 1.67-1.99 and OR 1.70, 95% CI 1.55-1.87 respectively).In addition hookah smoking had a borderline significant correlation with mild and moderate severity GERD symptoms in individuals who had never smoked cigarettes (OR 1.41, 95% CI 1.00-1.99 and OR 1.25, 95% CI 0.99-1.57 respectively). Overall this large study contributes useful data to inform the prevention and management of GERD symptoms particularly regarding the use of hookah, opium and nass which was previously unclear. Barbera M et al. The human squamous oesophagus has widespread capacity for clonal expansion from cells at diverse stages of differentiation. Gut 2014;0:1-9. doi:10.1136/gutjnl-2013-306171 Current knowledge on human esophageal tissue homeostasis and injury repair is derived predominantly from murine models and hence may be inaccurate due to cellular and architectural differences. This study used 3D imaging in conjunction withstaining for cell lineage markers to investigate the cellular mechanisms involved in homeostasis of the normal human squamous esophagus in 10 participants undergoing esophagectomy for esophageal cancer. The self-renewal potential of cell subpopulations was also assessed using in vitro and in vivo assays. A decreasing gradient of cell proliferation was observed from the inter-papillary basal layer to the tip of the papilla where there was no evidence of mitosis. The expression ofbeta1-integrin, a putative stem cell marker, was consistent throughout the basal layer and therefore the entire basal layer can be considered undifferentiated. Quiescent beta1 integrin/CD34-positive cells which failed to stain for CD45, S-100 or F4-80were identified at the tip of the papilla suggesting this is an extension of the basal layer. Contrary to previous data, this study found progenitor cells widely distributed in human esophageal tissue and included already differentiated epithelial cells. This insight into esophageal homeostasis may inform future studies exploring the pathological mechanisms underpinning homeostatic disruption in disease states such as Barrett's esophagus. Papers were prepared by: Drs Ishfaq Ahmad and Luke Materacki, Department of Medicine, Alexandra Hospital, Redditch, UK. PMID- 25110579 TI - Ten things to get right for marine conservation planning in the Coral Triangle. AB - Systematic conservation planning increasingly underpins the conservation and management of marine and coastal ecosystems worldwide. Amongst other benefits, conservation planning provides transparency in decision-making, efficiency in the use of limited resources, the ability to minimise conflict between diverse objectives, and to guide strategic expansion of local actions to maximise their cumulative impact. The Coral Triangle has long been recognised as a global marine conservation priority, and has been the subject of huge investment in conservation during the last five years through the Coral Triangle Initiative on Coral Reefs, Fisheries and Food Security. Yet conservation planning has had relatively little influence in this region. To explore why this is the case, we identify and discuss 10 challenges that must be resolved if conservation planning is to effectively inform management actions in the Coral Triangle. These are: making conservation planning accessible; integrating with other planning processes; building local capacity for conservation planning; institutionalising conservation planning within governments; integrating plans across governance levels; planning across governance boundaries; planning for multiple tools and objectives; understanding limitations of data; developing better measures of progress and effectiveness; and making a long term commitment. Most important is a conceptual shift from conservation planning undertaken as a project, to planning undertaken as a process, with dedicated financial and human resources committed to long-term engagement. PMID- 25120905 TI - Analysis of beta-N-methylamino-L-alanine (BMAA) in spirulina-containing supplements by liquid chromatography-tandem mass spectrometry. AB - Over the last decade the amino acid beta-N-methylamino-L-alanine (BMAA) has come under intense scrutiny. International laboratory and epidemiological research continues to support the hypothesis that environmental exposure to BMAA (e.g., through dietary practices, water supply) can promote the risk of various neurodegenerative diseases. A wide variety of cyanobacteria spp. have previously been reported to produce BMAA, with production levels dependent upon species, strain and environmental conditions. Since spirulina (Arthrospira spp.) is a member of the cyanobacteria phylum frequently consumed via dietary supplements, the presence of BMAA in such products may have public health implications. In the current work, we have analyzed ten spirulina-containing samples for the presence of BMAA; six pure spirulina samples from two separate raw materials suppliers, and four commercially-available multi-ingredient products containing 1.45 g of spirulina per 8.5 g serving. Because of controversy surrounding the measurement of BMAA, we have used two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods: one based on reversed phase LC (RPLC) with derivatization and the other based on hydrophilic interaction LC (HILIC). Potential matrix effects were corrected for by internal standardization using a stable isotope labeled BMAA standard. BMAA was not detected at low limits of detection (80 ng/g dry weight) in any of these product samples. Although these results are reassuring, BMAA analyses should be conducted on a wider sample selection and, perhaps, as part of ongoing spirulina production quality control testing and specifications. PMID- 25120903 TI - Vascular disruption and blood-brain barrier dysfunction in intracerebral hemorrhage. AB - This article reviews current knowledge of the mechanisms underlying the initial hemorrhage and secondary blood-brain barrier (BBB) dysfunction in primary spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are associated with ICH, for example, hypertension, Alzheimer's disease, vascular malformations and coagulopathies (genetic or drug-induced). After the initial bleed, there can be continued bleeding over the first 24 hours, so-called hematoma expansion, which is associated with adverse outcomes. A number of clinical trials are focused on trying to limit such expansion. Significant progress has been made on the causes of BBB dysfunction after ICH at the molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin, iron) and the inflammatory response to those components play a large role in ICH induced BBB dysfunction. There are current clinical trials of minimally invasive hematoma removal and iron chelation which may limit such dysfunction. Understanding the mechanisms underlying the initial hemorrhage and secondary BBB dysfunction in ICH is vital for developing methods to prevent and treat this devastating form of stroke. PMID- 25120908 TI - What can FGF23 do without Klotho? PMID- 25120907 TI - Quantitative phenotyping of bone fracture repair: a review. AB - Fracture repair is a complex process that involves the interaction of numerous molecular factors, cell lineages and tissue types. These biological processes allow for an impressive feat of engineering: an elastic soft callus is progressively replaced by a more rigid and mineralized callus. During this reparative phase, the healing bone is exposed to a risk of re-fracture. Bone volume and bone quality are the two major factors determining the strength of the callus. Although both factors are important, often only bone volume is analyzed and reported in preclinical studies. Recent developments in techniques for examining bone quality in the callus will enable the rapid and detailed analysis of its material properties and its microstructure. This review aims to give an overview of the methods available for quantitatively phenotyping the bone callus in preclinical studies such as Raman spectroscopy, nanoindentation, scanning acoustic microscopy, in vivo micro-computed tomography (micro-CT) and high resolution micro-CT. Consolidated and emerging experimental methods are described with a focus on their applicability, and with examples of their utilization. PMID- 25120909 TI - Instructions for producing a mouse model of glucocorticoid-induced osteoporosis. AB - Glucocorticoids are effective drugs used for the treatment of inflammatory diseases such as rheumatoid arthritis or asthma. Furthermore, they regulate various physiological processes, including bone remodeling. However, long-term high- and even low-dose glucocorticoid use is associated with a compromised bone quality and an increased fracture risk. At the cellular level, glucocorticoids suppress bone formation and stimulate bone resorption, which leads to loss of bone mass. To investigate the underlying mechanisms and new therapeutic strategies, the in vivo model for glucocorticoid-induced bone loss is widely used. This protocol outlines the common procedure that is currently used for the induction of bone loss in mice using glucocorticoids. It further provides useful hints and highlights possible pitfalls to take into account before starting an experiment. PMID- 25120906 TI - MicroRNAs as regulators of bone homeostasis and bone metastasis. AB - MicroRNAs (miRNAs) are short, endogenous RNAs that have essential roles in regulating gene expression through the disruption of target genes. The miRNA induced suppression can occur through Argonaute-mediated cleavage of target mRNAs or by translational inhibition. System-wide studies have underscored the integral role that miRNAs play in regulating the expression of essential genes within bone marrow stromal cells. The miRNA expression has been shown to enhance or inhibit cell differentiation and activity, and elucidating miRNA targets within bone marrow cells has revealed novel regulations during normal bone development. Importantly, multiple studies have shown that miRNA misexpression mediates the progression of bone-related pathologies, including osteopetrosis and osteoporosis, as well as the development and progression of osteosarcoma. Furthermore, recent studies have detailed the capacity for miRNAs to influence bone metastasis from a number of primary carcinomas. Taken together, these findings reveal the significant clinical potential for miRNAs to regulate bone homeostasis, as well as to mediate bone-related pathologies. PMID- 25120910 TI - Enhanced osteoblastogenesis in three-dimensional collagen gels. AB - Growth and differentiation of osteoblasts are often studied in cell cultures. In vivo, however, osteoblasts are embedded within a complex three-dimensional (3D) microenvironment, which bears little relation to standard culture flasks. Our study characterizes osteoblast-like cells cultured in 3D collagen gels and compares them with cells in two-dimensional (2D) cultures. Primary rat osteoblasts and MC3T3-E1 cells were seeded within type I collagen gels, and differentiation was determined by mineral staining and gene expression analysis. Cells growing in 3D gels showed positive mineral staining and induction of osteoblast marker genes earlier than cells growing in 2D. A number of genes, including osteocalcin, bone sialoprotein, alkaline phosphatase and dentin matrix protein 1, were already highly upregulated in 3D cultures 24 h after seeding. The early expression of osteoblast genes was dependent on the 3D structure and was not induced in cells growing on collagen-coated dishes in 2D. Comparison of thymidine incorporation between cells in 3D and 2D cultures treated with agents that induce proliferation-transforming growth factor beta, platelet-derived growth factor and lactoferrin-showed a much greater response in 3D gels. Cells in 3D cultures were also much more sensitive to inhibition of proliferation by the protein kinase inhibitor imatinib mesylate. The 3D collagen gels better represent the physiological bone environment and offer a number of technical advantages for the study of osteoblasts in vitro. These studies have additional practical implications as 3D collagen gels are considered as a scaffold material in regenerative medicine for the repair of bone defects. PMID- 25120913 TI - Need of surveillance response systems to combat Ebola outbreaks and other emerging infectious diseases in African countries. AB - There is growing concern in Sub-Saharan Africa about the spread of the Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, and the public health burden that it ensues. Since 1976, there have been 885,343 suspected and laboratory confirmed cases of EVD and the disease has claimed 2,512 cases and 932 fatality in West Africa. There are certain requirements that must be met when responding to EVD outbreaks and this process could incur certain challenges. For the purposes of this paper, five have been identified: (i) the deficiency in the development and implementation of surveillance response systems against Ebola and others infectious disease outbreaks in Africa; (ii) the lack of education and knowledge resulting in an EVD outbreak triggering panic, anxiety, psychosocial trauma, isolation and dignity impounding, stigmatisation, community ostracism and resistance to associated socio-ecological and public health consequences; (iii) limited financial resources, human technical capacity and weak community and national health system operational plans for prevention and control responses, practices and management; (iv) inadequate leadership and coordination; and (v) the lack of development of new strategies, tools and approaches, such as improved diagnostics and novel therapies including vaccines which can assist in preventing, controlling and containing Ebola outbreaks as well as the spread of the disease. Hence, there is an urgent need to develop and implement an active early warning alert and surveillance response system for outbreak response and control of emerging infectious diseases. Understanding the unending risks of transmission dynamics and resurgence is essential in implementing rapid effective response interventions tailored to specific local settings and contexts. THEREFORE, THE FOLLOWING ACTIONS ARE RECOMMENDED: (i) national and regional inter sectorial and trans-disciplinary surveillance response systems that include early warnings, as well as critical human resources development, must be quickly adopted by allied ministries and organisations in African countries in epidemic and pandemic responses; (ii) harnessing all stakeholders commitment and advocacy in sustained funding, collaboration, communication and networking including community participation to enhance a coordinated responses, as well as tracking and prompt case management to combat challenges; (iii) more research and development in new drug discovery and vaccines; and (iv) understanding the involvement of global health to promote the establishment of public health surveillance response systems with functions of early warning, as well as monitoring and evaluation in upholding research-action programmes and innovative interventions. PMID- 25120911 TI - The reversal phase of the bone-remodeling cycle: cellular prerequisites for coupling resorption and formation. AB - The reversal phase couples bone resorption to bone formation by generating an osteogenic environment at remodeling sites. The coupling mechanism remains poorly understood, despite the identification of a number of 'coupling' osteogenic molecules. A possible reason is the poor attention for the cells leading to osteogenesis during the reversal phase. This review aims at creating awareness of these cells and their activities in adult cancellous bone. It relates cell events (i) on the bone surface, (ii) in the mesenchymal envelope surrounding the bone marrow and appearing as a canopy above remodeling surfaces and (iii) in the bone marrow itself within a 50-MUm distance of this canopy. When bone remodeling is initiated, osteoprogenitors at these three different levels are activated, likely as a result of a rearrangement of cell-cell and cell-matrix interactions. Notably, canopies are brought under the osteogenic influence of capillaries and osteoclasts, whereas bone surface cells become exposed to the eroded matrix and other osteoclast products. In several diverse pathophysiological situations, including osteoporosis, a decreased availability of osteoprogenitors from these local reservoirs coincides with decreased osteoblast recruitment and impaired initiation of bone formation, that is, uncoupling. Overall, this review stresses that coupling does not only depend on molecules able to activate osteogenesis, but that it also demands the presence of osteoprogenitors and ordered cell rearrangements at the remodeling site. It points to protection of local osteoprogenitors as a critical strategy to prevent bone loss. PMID- 25120914 TI - Changes in sex difference in swimming speed in finalists at FINA World Championships and the Olympic Games from 1992 to 2013. AB - BACKGROUND: This study investigated swimming speeds and sex differences of finalists competing at the Olympic Games (i.e. 624 female and 672 male athletes) and FINA World Championships (i.e. 990 women and 1008 men) between 1992 and 2013. METHODS: Linear, non-linear and multi-level regression models were used to investigate changes in swimming speeds and sex differences for champions and finalists. RESULTS: Regarding finalists in FINA World Championships and Olympic Games, swimming speed increased linearly in both women and men in all disciplines and race distances. Male world champions' swimming speed remained stable in 200 m butterfly, 400 m, 800 m and 1,500 m freestyle. Considering women, swimming speed remained unchanged in 50 m and 400 m freestyle. In the Olympic Games, swimming speed of male champions remained unchanged in 200 m breaststroke, 50 m, 400 m, 800 m and 1,500 m freestyle. Female Olympic champions' swimming speed remained stable in 100 m and 200 m backstroke, 100 m butterfly, 200 m individual medley, 50 m and 200 m freestyle. Evaluating sex differences between finalists in FINA World Championships, results showed a linear decrease in 100 m breaststroke and 200 m butterfly and a non-linear increase in 100 m backstroke. In finals at the Olympic Games, the sex difference decreased linearly for 100 m backstroke, 400 m and 800 m freestyle. However, a linear increase for 200 m butterfly can be reported. Considering Olympic and world champions, the sex difference remained stable in all disciplines and race distances. CONCLUSION: Swimming speed of the finalists at the Olympic Games and FINA World Championships increased linearly. The top annual female swimmers increased swimming speed rather at longer race distances (i.e. 800 m and 1,500 m freestyle, 200 m butterfly, and 400 m individual medley), whereas the top annual male swimmers increased it rather at shorter race distances (i.e. 100 m and 200 m freestyle, 100 m butterfly, and 100 m breaststroke). Sex difference in swimming was unchanged in Olympic and world champions. Finalists and champions at the Olympic Games and FINA World Championships reduced the sex difference with increasing race distance. PMID- 25120915 TI - Relationship between age and elite marathon race time in world single age records from 5 to 93 years. AB - BACKGROUND: The aims of the study were (i) to investigate the relationship between elite marathon race times and age in 1-year intervals by using the world single age records in marathon running from 5 to 93 years and (ii) to evaluate the sex difference in elite marathon running performance with advancing age. METHODS: World single age records in marathon running in 1-year intervals for women and men were analysed regarding changes across age for both men and women using linear and non-linear regression analyses for each age for women and men. RESULTS: The relationship between elite marathon race time and age was non-linear (i.e. polynomial regression 4(th) degree) for women and men. The curve was U shaped where performance improved from 5 to ~20 years. From 5 years to ~15 years, boys and girls performed very similar. Between ~20 and ~35 years, performance was quite linear, but started to decrease at the age of ~35 years in a curvilinear manner with increasing age in both women and men. The sex difference increased non-linearly (i.e. polynomial regression 7(th) degree) from 5 to ~20 years, remained unchanged at ~20 min from ~20 to ~50 years and increased thereafter. The sex difference was lowest (7.5%, 10.5 min) at the age of 49 years. CONCLUSION: Elite marathon race times improved from 5 to ~20 years, remained linear between ~20 and ~35 years, and started to increase at the age of ~35 years in a curvilinear manner with increasing age in both women and men. The sex difference in elite marathon race time increased non-linearly and was lowest at the age of ~49 years. PMID- 25120916 TI - Cervical isometric strength and range of motion of elite rugby union players: a cohort study. AB - BACKGROUND: Head and neck injury is relatively common in Rugby Union. Despite this, strength and range-of-motion characteristics of the cervical spine are poorly characterised. The aim of this study was to provide data on the strength and range-of-motion of the cervical spine of professional rugby players to guide clinical rehabilitation. METHODS: A cohort study was performed evaluating 27 players from a single UK professional rugby club. Cervical isometric strength and range-of-motion were assessed in 3 planes of reference. Anthropometric data was collected and multivariate regression modelling performed with a view to predicting cervical isometric strength. RESULTS: Largest forces were generated in extension, with broadly equal isometric side flexion forces at around 90% of extension values. The forwards generated significantly more force than the backline in all parameters bar flexion. The forwards had substantially reduced cervical range-of-motion and larger body mass, with differences observed in height, weight, neck circumference and chest circumference (p < 0.002). Neck circumference was the sole predictor of isometric extension (adjusted R(2) = 30.34). CONCLUSION: Rehabilitative training programs aim to restore individuals to pre-injury status. This work provides reference ranges for the strength and range of motion of the cervical spine of current elite level rugby players. PMID- 25120917 TI - Reforming Cardiovascular Care in the United States towards High-Quality Care at Lower Cost with Examples from Model Programs in the State of Michigan. AB - Despite its status as a world leader in treatment innovation and medical education, a quality chasm exists in American health care. Care fragmentation and poor coordination contribute to expensive care with highly variable quality in the United States. The rising costs of health care since 1990 have had a huge impact on individuals, families, businesses, the federal and state governments, and the national budget deficit. The passage of the Affordable Care Act represents a large shift in how health care is financed and delivered in the United States. The objective of this review is to describe some of the economic and social forces driving health care reform, provide an overview of the Patient Protection and Affordable Care Act (ACA), and review model cardiovascular quality improvement programs underway in the state of Michigan. As health care reorganization occurs at the federal level, local and regional efforts can serve as models to accelerate improvement toward achieving better population health and better care at lower cost. Model programs in Michigan have achieved this goal in cardiovascular care through the systematic application of evidence-based care, the utilization of regional quality improvement collaboratives, community-based childhood wellness promotion, and medical device-based competitive bidding strategies. These efforts are examples of the direction cardiovascular care delivery will need to move in this era of the Affordable Care Act. PMID- 25120918 TI - A new paradigm is needed for medical education in the mid-twenty-first century and beyond: are we ready? AB - The twentieth century witnessed profound changes in medical education. All these changes, however, took place within the existing framework, suggested by Flexner a century ago. The present paper suggests that we are approaching a singularity point, where we shall have to change the paradigm and be prepared for an entirely new genre of medical education. This suggestion is based upon analysis of existing and envisaged trends: first, in technology, such as availability of information and sophisticated simulations; second, in medical practice, such as far-reaching interventions in life and death that create an array of new moral dilemmas, as well as a change in patient mix in hospitals and a growing need of team work; third, in the societal attitude toward higher education. The structure of the future medical school is delineated in a rough sketch, and so are the roles of the future medical teacher. It is concluded that we are presently not prepared for the approaching changes, neither from practical nor from attitudinal points of view, and that it is now high time for both awareness of and preparation for these changes. PMID- 25120920 TI - Delivering bad news: an approach according to jewish scriptures. AB - Despite a preoccupation in the medical literature with developing an effective approach for breaking bad news, the sources are based on personal opinion alone and only in some instances on qualitative research. Recognizing the gravity of this topic coupled with respect for the wisdom of the written and oral Jewish scriptures, this work is an attempt to delve into the diverse ancient writings to draw conclusions regarding a recommended methodology to guide and inform this task. It is interesting to learn that most elements related to this topic have previously been raised in various forms in the scriptures. The issues range from where, when, and how the bearer of bad news should undertake this duty, to details such as the environment, the format, the speed, and depth of the details to be disclosed. The essence of this paper is to enrich the reader using both positive and negative examples found in the Jewish heritage. Adopting these principles will hopefully provide an effective method for performing this unpleasant obligation, with the goal of limiting harmful consequences as much as possible. PMID- 25120919 TI - The perils of complementary alternative medicine. AB - More than 11,000 articles lauding alternative medicine appear in the PubMed database, but there are only a few articles describing the complications of such care. Two patients suffering from complications of alternative medicine were treated in our hospital: one patient developed necrotizing fasciitis after acupuncture, and the second developed an epidural hematoma after chiropractic manipulation. These complications serve as a clarion call to the Israeli Health Ministry, as well as to health ministries around the world, to include complementary medicine under its inspection and legislative authority. PMID- 25120921 TI - Spermatocytic variant of classic seminoma: a report of five cases and a brief review of the literature. AB - BACKGROUND: Spermatocytic seminoma is a rare testicular malignancy, appearing in the adult population. It has a good prognosis and a low rate of metastatic potential. OBJECTIVES: We present five cases diagnosed and treated with radiotherapy at Rambam Health Care Campus in Haifa, Israel. METHODS: Between 1974 and 1996, five patients with stage I spermatocytic seminoma were referred post orchiectomy to the Northern Israel Oncology Center. All five patients presented with the typical pathological features of the spermatocytic variant of classic seminoma, and all were staged clinically and radiologically. RESULTS: Mean age at diagnosis was 44 years (range 30-58 years). Main symptoms included a palpable testicular mass and/or testicular enlargement. Mean duration of symptoms was 9 months (range 0.5-24 months). Three patients were irradiated to the para aortic/ipsilateral iliacal lymph nodes (mean total dose 2,500 cGy), one patient with 4,000 cGy. One patient was irradiated to the bilateral iliacal lymph nodes (2,600 cGy). With a median follow-up of 15 years, four patients are alive with no evidence of disease or severe late side effects. One patient developed severe lymphedema and symptomatic peripheral vascular disease, stage IIA prostate carcinoma (hormonal and brachytherapy treatment) and a non-secretory hypophyseal adenoma (surgically removed); he died at the age of 75 due to severe peripheral vascular and coronary heart disease with no evidence of his first or second primaries. CONCLUSIONS: Prognosis is excellent and does not differ from classic seminoma. As in the accumulated experience in early-stage, low-risk classic seminoma, we suggest surveillance as the preferred policy. PMID- 25120922 TI - Vulvar cancer in the north of Israel. AB - PURPOSE: This is a population study of patients who were treated for vulvar cancer in a tertiary center in northern Israel, aimed to report clinical findings, treatment, and outcome. METHODS: A retrospective chart review of all medical records of consecutive patients who were treated for vulvar cancer in the years 1993-2012 was conducted. Data extracted from the medical records included demographics, histology, size of lesion, stage of disease at diagnosis, type of treatment, radiation dose, follow-up, recurrence, and survival. RESULTS: The study included 44 patients with a median age of 69.8 years (range, 42-93 years). Thirty-five (79.5%) of the patients were of Jewish descent, five were Arabic, and four were of other descent. The most common histology type was squamous cell carcinoma in 35 (79.5%) patients. Most patients were staged FIGO II-III at time of diagnosis. Surgery was the most common primary treatment modality (54.2%). Twenty-three (52.2%) patients had recurrent disease. Older age and more advanced stage at diagnosis were associated with increased mortality. CONCLUSION: Vulvar cancer is common among elderly women with co-morbidities who present in advanced disease stage; all these factors are significant for survival. PMID- 25120923 TI - Hitler's Jewish Physicians. AB - The mystery behind the behavior of infamous personalities leaves many open questions, particularly when related to the practice of medicine. This paper takes a brief look at two Jewish physicians who played memorable roles in the life of Adolf Hitler. PMID- 25120925 TI - Interaction of ingested leucine with glycine on insulin and glucose concentrations. AB - The majority of individual amino acids increase insulin and attenuate the plasma glucose response when ingested with glucose. Objective. To determine whether ingestion of two amino acids simultaneously, with glucose, would result in an additive effect. Leucine (Leu) and glycine (Gly) were chosen because they were two of the most potent glucose-lowering amino acids when given individually. Materials and Methods. Nine subjects received test items on four separate days. The first was a water control, then 25 g glucose, or Leu + Gly (1 mmol/kg fat free mass each) +/-25 g glucose, in random order. Glucose, insulin, and glucagon were measured frequently for 2.5 hours. Net areas were calculated. Results. The glucose area response decreased by 66%. The insulin area response increased by 24% after ingestion of Leu + Gly + glucose compared to ingestion of glucose alone. The decrease in glucose response was not additive; the increase in insulin response was far less than additive when compared to previously published individual amino acid results. The glucagon concentration remained unchanged. Conclusion. There is an interaction between Leu and Gly that results in a markedly attenuated glucose response. This occurred with a very modest increase in insulin response. Changes in glucagon response could not explain the results. The mechanism is unknown. PMID- 25120924 TI - A Clinical and Confocal Microscopic Comparison of Transepithelial PRK and LASEK for Myopia. AB - Purpose. To compare the clinical and confocal microscopic results of transepithelial PRK versus LASEK for correction of myopia. Materials and Methods. Twelve patients with myopia received transepithelial PRK in one eye and LASEK in the other. In transepithelial PRK-treated eyes, the corneal epithelium was removed with 40 microns of excimer laser ablation and in LASEK-treated eyes with 25-second application of 18% ethanol. Time to epithelial healing, ocular discomfort, uncorrected and best corrected visual acuities, manifest refraction, haze, greyscale value, and keratocyte apoptosis in confocal microscopy were recorded. Results. The mean time to epithelial healing was significantly longer after LASEK (4.00 +/- 0.43 versus 3.17 +/- 0.6 days). On day 1, ocular discomfort was significantly higher after transepithelial PRK. The grade of haze, keratocyte apoptosis, and greyscale value in confocal microscopy were significantly higher in transepithelial PRK-treated eyes at 1 month. All transepithelial PRK- and LASEK-treated eyes achieved 20/25 or better UCVA and were within +/-1.00 D of emmetropia at final visits. Conclusions. Both transepithelial PRK and LASEK offer effective correction of myopia at 1 year. However, LASEK appeared to induce less discomfort and less intense wound healing in the early postoperative period. PMID- 25120926 TI - Sequential Statistical Optimization of Media Components for the Production of Glucoamylase by Thermophilic Fungus Humicola grisea MTCC 352. AB - Glucoamylase is an industrially important enzyme which converts soluble starch into glucose. The media components for the production of glucoamylase from thermophilic fungus Humicola grisea MTCC 352 have been optimized. Eight media components, namely, soluble starch, yeast extract, KH2PO4, K2HPO4, NaCl, CaCl2, MgSO4 .7H2O, and Vogel's trace elements solution, were first screened for their effect on the production of glucoamylase and only four components (soluble starch, yeast extract, K2HPO4, and MgSO4 .7H2O) were identified as statistically significant using Plackett-Burman design. It was fitted into a first-order model (R (2) = 0.9859). Steepest ascent method was performed to identify the location of optimum. Central composite design was employed to determine the optimum values (soluble starch: 28.41 g/L, yeast extract: 9.61 g/L, K2HPO4: 2.42 g/L, and MgSO4 .7H2O: 1.91 g/L). The experimental activity of 12.27 U/mL obtained was close to the predicted activity of 12.15. High R (2) value (0.9397), low PRESS value (9.47), and AARD values (2.07%) indicate the accuracy of the proposed model. The glucoamylase production was found to increase from 4.57 U/mL to 12.27 U/mL, a 2.68-fold enhancement, as compared to the unoptimized medium. PMID- 25120927 TI - Applying Theory to Understand and Modify Nurse Intention to Adhere to Recommendations regarding the Use of Filter Needles: An Intervention Mapping Approach. AB - The manipulation of glass ampoules involves risk of particle contamination of parenteral medication, and the use of filter needles has often been recommended in order to reduce the number of particles in these solutions. This study aims to develop a theory-based intervention to increase nurse intention to use filter needles according to clinical guideline recommendations produced by a large university medical centre in Quebec (Canada). Using the Intervention Mapping framework, we first identified the psychosocial determinants of nurse intention to use filter needles according to these recommendations. Second, we developed and implemented an intervention targeting nurses from five care units in order to increase their intention to adhere to recommendations on the use of filter needles. We also assessed nurse satisfaction with the intervention. In total, 270 nurses received the intervention and 169 completed the posttest questionnaire. The two determinants of intention, that is, attitude and perceived behavioral control, were significantly higher after the intervention, but only perceived behavioral control remained a predictor of intention. In general, nurses were highly satisfied with the intervention. This study provides support for the use of Intervention Mapping to develop, implement, and evaluate theory-based interventions in order to improve healthcare professional adherence to clinical recommendations. PMID- 25120929 TI - Retracted: Peripheral cytokines as a chemical mediator for postconcussion like sickness behaviour in trauma and perioperative patients: literature review. PMID- 25120928 TI - Effects of inactivated Bordetella pertussis on phosphodiesterase in the lung of ovalbumin sensitized and challenged rats. AB - This paper indicated that inactivated Bordetella pertussis (iBp) can enhance the lung airway hyperreactivity of the rats sensitized and challenged with OVA. The mechanisms were involved in the upregulation of cAMP-PDE activity and PDE4A, PDE4D, and PDE3 gene expression in the lungs. But only PDE4 activity was different between the OVA and OVA+iBp groups, and PDE4D expression was significantly increased in iBp rats alone. So, our data suggested that cosensitization with OVA and iBp affects lung airway reactivity by modulating the lung cAMP-PDE activity and PDE4D gene expression. PMID- 25120930 TI - Performing chest x-rays at inspiration in uncooperative children: the effect of exercises with a training program for radiology technicians. AB - Objective. It is difficult to acquire a chest X-ray of a crying infant at maximum inspiration. A computer program was developed for technician training. Method. Video clips of 3 babies were used and the moment of deepest inspiration was determined in the single-frame view. 12 technicians simulated chest radiographs at normal video speed by pushing a button. The computer program stopped the video and calculated the period of time to the optimal instant for a chest X-ray. Demonstration software can be tested at website online. Every technician simulated 10 chest X-rays for each of the 3 video clips. The technicians then spent 40 minutes practicing performing chest X-rays at optimal inspiration. The test was repeated after 5, 20, and 40 minutes of practice. Results. 6 participants showed a significant improvement after exercises (collective 1). Deviation from the optimal instant for taking an X-ray at inspiration decreased from 0.39 to 0.22 s after 40 min of practice. 6 technicians showed no significant improvement (collective 2). Deviation decreased from a low starting value of 0.25 s to 0.21 s. Conclusion. The tested computer program improves the ability of radiology technicians to take a chest X-ray at optimal inspiration in a crying child. PMID- 25120931 TI - The Influence of DNA Extraction Procedure and Primer Set on the Bacterial Community Analysis by Pyrosequencing of Barcoded 16S rRNA Gene Amplicons. AB - In this study, the effect of different DNA extraction procedures and primer sets on pyrosequencing results regarding the composition of bacterial communities in the ileum of piglets was investigated. Ileal chyme from piglets fed a diet containing different amounts of zinc oxide was used to evaluate a pyrosequencing study with barcoded 16S rRNA PCR products. Two DNA extraction methods (bead beating versus silica gel columns) and two primer sets targeting variable regions of bacterial 16S rRNA genes (8f-534r versus 968f-1401r) were considered. The SEED viewer software of the MG-RAST server was used for automated sequence analysis. A total of 5.2 * 10(5) sequences were used for analysis after processing for read length (150 bp), minimum sequence occurrence (5), and exclusion of eukaryotic and unclassified/uncultured sequences. DNA extraction procedures and primer sets differed significantly in total sequence yield. The distribution of bacterial order and main bacterial genera was influenced significantly by both parameters. However, this study has shown that the results of pyrosequencing studies using barcoded PCR amplicons of bacterial 16S rRNA genes depend on DNA extraction and primer choice, as well as on the manner of downstream sequence analysis. PMID- 25120932 TI - Concomitant Colonization of Helicobacter pylori in Dental Plaque and Gastric Biopsy. AB - Frequently reported H. pylori antimicrobial therapy failures suggest that there might be a different niche where the bacteria can stay safe. Current study aims to examine potential role of oral colonization of H. pylori to feed reinfection after primary therapy. However, patients who were admitted to the gastroscopy section were chosen and gastric biopsy and dental plaque specimens were collected. Molecular and biochemical tests were applied to confirm H. pylori identity in different colonization niches. Results showed that 88.8% of dyspeptic patients had epigastric pains with nocturnal awakening when they were hungry (P = 0.023). All patients who received therapy already were again H. pylori positive while they are still carrying H. pylori in dental plaque (P = 0.001). Moreover, H. pylori infection was sought in 100% of gastric biopsy's dyspeptic patients who had ulcerated esophagitis and erosive duodenitis and who were H. pylori positive, and 75% of dyspeptic patients with duodenum deformity had this bacterium in gastric biopsies (P = 0.004). Present study showed that only successful eradication of gastric H. pylori cannot guarantee prevention of reinfection. Conclusively, a new strategy which indicates concomitant eradication in oral and gastric colonization can result in clearance of H. pylori infection. PMID- 25120933 TI - Robotic radical prostatectomy in patients with previous prostate surgery and radiotherapy. AB - Herein, we will review the available literature about robot-assisted radical prostatectomy in patients who have undergone prostate surgery or radiotherapy. Current data about this topic consists of small case series with limited follow up. Despite being technically demanding, robot-assisted radical prostatectomy (RARP) can be considered feasible in either setting. Prostate surgery or prostatic irradiation should not be considered as a contraindication for robot assisted radical prostatectomy. Nevertheless, patient counseling about the possible complications and the need for reintervention is of extreme importance in this patient population. Early oncologic and functional results of RARP performed in case of radiorecurrent prostate cancer look promising. Regarding postprostate surgery RARP, some series have reported comparable results, while some have demonstrated more inferior outcomes than those of naive cases. In order to assess the exact functional and oncologic outcome of RARP in patients with previous prostate surgery and radiotherapy, studies enrolling higher number of patients and providing longer follow-up data are needed. PMID- 25120935 TI - Pneumoperitoneum with subcutaneous emphysema after percutaneous endoscopic gastrostomy. AB - Percutaneous endoscopic gastrostomy is a safe way for enteral nutrition in selected patients. Generally, complications of this procedure are very rare but due to patients general health condition, delayed diagnosis and treatment of complications can be life threatening. In this study, we present a PEG-related massive pneumoperitoneum and subcutaneous emphysema in a patient with neuro Behcet. PMID- 25120934 TI - Tinnitus-related distress and the personality characteristic resilience. AB - It has been suggested that personality traits may be prognostic for the severity of suffering from tinnitus. Resilience as measured with the Wagnild and Young resilience scale represents a positive personality characteristic that promotes adaptation to adverse life conditions including chronic health conditions. Aim of the study was to explore the relation between resilience and tinnitus severity. In a cross-sectional study with a self-report questionnaire, information on tinnitus-related distress and subjective tinnitus loudness was recorded together with the personality characteristic resilience and emotional health, a measure generated from depression, anxiety, and somatic symptom severity scales. Data from 4705 individuals with tinnitus indicate that tinnitus-related distress and to a lesser extent the experienced loudness of the tinnitus show an inverse correlation with resilience. A mediation analysis revealed that the relationship between resilience and tinnitus-related distress is mediated by emotional health. This indirect effect indicates that high resilience is associated with better emotional health or less depression, anxiety, and somatic symptom severity, which in turn is associated with a less distressing tinnitus. Validity of resilience as a predictor for tinnitus-related distress is supported but needs to be explored further in longitudinal studies including acute tinnitus patients. PMID- 25120936 TI - Cutaneous Metastases from Primary Hepatobiliary Tumors as the First Sign of Tumor Recurrence following Liver Transplantation. AB - Cutaneous metastasis from hepatobiliary tumors is a rare event, especially following liver transplantation. We report our experience with two cases of cutaneous metastases from both hepatocellular carcinoma and mixed hepatocellular/cholangiocarcinoma following liver transplantation, along with a review of the literature. PMID- 25120937 TI - A rare cause of testicular metastasis: upper tract urothelial carcinoma. AB - Metastatic testicular cancers are rare. Primary tumor sources are prostate, lung, and gastrointestinal tract for metastatic testicular cancers. Metastasis of urothelial carcinoma (UC) to the testis is extremely rare. Two-thirds of upper tract urothelial carcinoma (UTUC) is of invasive stage at diagnosis and metastatic sites are the pelvic lymph nodes, liver, lung, and bone. We report a rare case of metastatic UTUC to the testis which has not been reported before, except one case in the literature. Testicular metastasis of UC should be considered in patients with hematuria and testicular swelling. PMID- 25120938 TI - Forearm compartment syndrome caused by reperfusion injury. AB - Compartment syndrome is commonly seen following lower extremity ischemia. However, upper extremities' compartment syndrome, especially after any vascular surgical procedures, is infrequent. Herein we report a case of an acute forearm compartment syndrome that was developed after delayed brachial artery embolectomy. PMID- 25120939 TI - Do improvements in balance relate to improvements in long-distance walking function after stroke? AB - Stroke survivors identify a reduced capacity to walk farther distances as a factor limiting their engagement at home and in community. Previous observational studies have shown that measures of balance ability and balance self-efficacy are strong predictors of long-distance walking function after stroke. Consequently, recommendations to target balance during rehabilitation have been put forth. The purpose of this study was to determine if the changes in balance and long distance walking function observed following a 12-week poststroke walking rehabilitation program were related. For thirty-one subjects with hemiparesis after stroke, this investigation explored the cross-sectional (i.e., before training) and longitudinal (i.e., changes due to intervention) relationships between measures of standing balance, walking balance, and balance self-efficacy versus long-distance walking function as measured via the 6-minute walk test (6MWT). A regression model containing all three balance variables accounted for 60.8% of the variance in 6MWT performance (adj R (2) = .584; F(3,27) = 13.931; P < .001); however, only dynamic balance (FGA) was an independent predictor (beta = .502) of 6MWT distance. Interestingly, changes in balance were unrelated to changes in the distance walked (each correlation coefficient <.17, P > .05). For persons after stroke similar to those studied, improving balance may not be sufficient to improve long-distance walking function. PMID- 25120940 TI - Y-Stenting for Bifurcation Aneurysm Coil Embolization: What is the Risk? AB - The use of two stents in a "Y" configuration (Y-stenting) to assist with coil embolization of complex bifurcation aneurysms has been accepted as an alternative to clip reconstruction of a select subset of challenging aneurysms. We review the risks associated with Y-stenting, including its procedural complication rates, angiographic occlusion rates, rerupture, and retreatment rates. PMID- 25120941 TI - Deep brain stimulation for tremor associated with underlying ataxia syndromes: a case series and discussion of issues. AB - BACKGROUND: Deep brain stimulation (DBS) has been utilized to treat various symptoms in patients suffering from movement disorders such as Parkinson's disease, dystonia, and essential tremor. Though ataxia syndromes have not been formally or frequently addressed with DBS, there are patients with ataxia and associated medication refractory tremor or dystonia who may potentially benefit from therapy. METHODS: A retrospective database review was performed, searching for cases of ataxia where tremor and/or dystonia were addressed by utilizing DBS at the University of Florida Center for Movement Disorders and Neurorestoration between 2008 and 2011. Five patients were found who had DBS implantation to address either medication refractory tremor or dystonia. The patient's underlying diagnoses included spinocerebellar ataxia type 2 (SCA2), fragile X associated tremor ataxia syndrome (FXTAS), a case of idiopathic ataxia (ataxia not otherwise specified [NOS]), spinocerebellar ataxia type 17 (SCA17), and a senataxin mutation (SETX). RESULTS: DBS improved medication refractory tremor in the SCA2 and the ataxia NOS patients. The outcome for the FXTAS patient was poor. DBS improved dystonia in the SCA17 and SETX patients, although dystonia did not improve in the lower extremities of the SCA17 patient. All patients reported a transient gait dysfunction postoperatively, and there were no reports of improvement in ataxia-related symptoms. DISCUSSION: DBS may be an option to treat tremor, inclusive of dystonic tremor in patients with underlying ataxia; however, gait and other symptoms may possibly be worsened. PMID- 25120942 TI - Observational Study of IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm (XCiDaBLE): Interim Results for the First 170 Subjects with Blepharospasm. AB - BACKGROUND: XCiDaBLE is a large, prospective, observational "naturalistic" study evaluating Xeomin(r) for Cervical Dystonia or BLEpharospasm in the United States. We report the interim results from the blepharospasm cohort of XCiDaBLE. METHODS: Subjects (?18 years old) with blepharospasm were followed for two treatment cycles of incobotulinumtoxinA and monitored for 4 weeks after injection via interactive voice/web response system (IVRS/IWRS). The investigator-reported scale includes the Clinical Global Impression Scale-Severity subscale (CGI-S). Patient-reported outcome measures include the Patient Global Impression Scale Severity (PGI-S) and -Improvement (PGI-I) subscales, Jankovic Rating Scale (JRS), SF-12v2(r) health survey, and Work Productivity and Activity Impairment questionnaire. Subjects are seen by the investigator at baseline (including the first injection), during the second injection, and at a final study visit (12 weeks after the second injection). RESULTS: One hundred seventy subjects were included in this interim analysis. The majority of subjects were female (77.1%) and white (91.8%), and had previously been treated with botulinum toxins (96.5%). The mean total dose (both eyes) was 71.5 U of incobotulinumtoxinA for the first injection. PGI-S, PGI-I, and JRS scores were significantly improved 4 weeks after treatment (all p<0.0001). No differences were noted in either quality of life (QoL) or work productivity in this short assessment period. No unexpected adverse events occurred. DISCUSSION: This is an interim study and assessment method based on an IVRS/IWRS. In this predominantly toxin-experienced cohort, significant benefits in specific and global measures of disease severity were seen in the immediate post-incobotulinumtoxinA injection period. It will be interesting to see if there are improvements in QoL with consistent individualized injections over a longer period. PMID- 25120944 TI - The GABA Hypothesis in Essential Tremor: Lights and Shadows. AB - BACKGROUND: The gamma-aminobutyric acid (GABA) hypothesis in essential tremor (ET) implies a disturbance of the GABAergic system, especially involving the cerebellum. This review examines the evidence of the GABA hypothesis. METHODS: The review is based on published data about GABA dysfunction in ET, taking into account studies on cerebrospinal fluid, pathology, electrophysiology, genetics, neuroimaging, experimental animal models, and human drug therapies. RESULTS: Findings from several studies support the GABA hypothesis in ET. The hypothesis follows four steps: 1) cerebellar neurodegeneration with Purkinje cell loss; 2) a decrease in GABA system activity in deep cerebellar neurons; 3) disinhibition in output deep cerebellar neurons with pacemaker activity; and 4) an increase in rhythmic activity of the thalamus and thalamo-cortical circuit, contributing to the generation of tremor. Doubts have been cast on this hypothesis, however, by the fact that it is based on relatively few works, controversial post-mortem findings, and negative genetic studies on the GABA system. Furthermore, GABAergic drug efficacy is low and some GABAergic drugs do not have antitremoric efficacy. DISCUSSION: The GABA hypothesis continues to be the most robust pathophysiological hypothesis to explain ET. There is light in all GABA hypothesis steps, but a number of shadows cannot be overlooked. We need more studies to clarify the neurodegenerative nature of the disease, to confirm the decrease of GABA activity in the cerebellum, and to test more therapies that enhance the GABA transmission specifically in the cerebellum area. PMID- 25120945 TI - The Non-motor Features of Essential Tremor: A Primary Disease Feature or Just a Secondary Phenomenon? AB - Essential tremor (ET) is a pathologically heterogeneous neurodegenerative disorder with both motor and increasingly recognized non-motor features. It is debated whether the non-motor manifestations in ET result from widespread neurodegeneration or are merely secondary to impaired motor functions and decreased quality of life due to tremor. It is important to review these features to determine how to best treat the non-motor symptoms of patients and to understand the basic pathophysiology of the disease and develop appropriate pharmacotherapies. In this review, retrospective and prospective clinical studies were critically analyzed to identify possible correlations between the severities of non-motor features and tremor. We speculated that if such a correlation existed, the non-motor features were likely to be secondary to tremor. According to the current literature, the deficits in executive function, attention, concentration, and memory often observed in ET are likely to be a primary manifestation of the disease. It has also been documented that patients with ET often exhibit characteristic personality traits. However, it remains to be determined whether the other non-motor features often seen in ET, such as anxiety, depression, and sleep disturbances are primary or secondary to motor manifestations of ET and subsequent poor quality of life. Finally, there is evidence that patients with ET can also have impaired color vision, disturbances of olfaction, and hearing impairments, though there are few studies in these areas. Further investigations of large cohorts of patients with ET are required to understand the prevalence, nature, and true significance of the non-motor features in ET. PMID- 25120943 TI - Essential tremor: a neurodegenerative disease? AB - BACKGROUND: Essential tremor (ET) is one of the most common neurological disorders among adults, and is the most common of the many tremor disorders. It has classically been viewed as a benign monosymptomatic condition, yet over the past decade, a growing body of evidence indicates that ET is a progressive condition that is clinically heterogeneous, as it may be associated with a spectrum of clinical features, with both motor and non-motor elements. In this review, I will describe the most significant emerging milestones in research which, when taken together, suggest that ET is a neurodegenerative condition. METHODS: A PubMed search conducted in June 2014 crossing the terms "essential tremor" (ET) and "neurodegenerative" yielded 122 entries, 20 of which included the term "neurodegenerative" in the article title. This was supplemented by articles in the author's files that pertained to this topic. RESULTS/DISCUSSION: There is an open and active dialogue in the medical community as to whether ET is a neurodegenerative disease, with considerable evidence in favor of this. Specifically, ET is a progressive disorder of aging associated with neuronal loss (reduction in Purkinje cells) as well as other post-mortem changes that occur in traditional neurodegenerative disorders. Along with this, advanced neuroimaging techniques are now demonstrating distinct structural changes, several of which are consistent with neuronal loss, in patients with ET. However, further longitudinal clinical and neuroimaging longitudinal studies to assess progression are required. PMID- 25120946 TI - Mirror movements identified in patients with moebius syndrome. AB - BACKGROUND: Moebius syndrome is a rare disorder with minimum clinical criteria of congenital facial weakness in association with impairment in abduction of one or both eyes. Mirror movements are not known to be associated with Moebius syndrome. CASE REPORT: We present three patients who meet minimum criteria for a diagnosis of Moebius syndrome and who also display mirror movements. DISCUSSION: This case series suggests that Moebius syndrome may be associated with mirror movements. Further investigation to delineate the genetic etiologies of Moebius syndrome is ongoing. Patients with Moebius syndrome and mirror movements may represent a specific subclass of this disorder. PMID- 25120947 TI - Assessment of the effect of Schistosoma haematobium co infection on malaria parasites and immune responses in rural populations in Gabon: study protocol. AB - BACKGROUND: Malaria and helminth co infection are common in tropical and subtropical areas where they affect the life of millions of people. While both helminth and malaria parasites have immunomodulatory activities, little is known about the consequence of co-infections on malaria antigen specific immune responses. METHOD/DESIGN: This study will be conducted in two rural areas of the Moyen Ogooue province in Gabon, endemic for both Plasmodium falciparum and Schistosoma haematobium infections. Participants, 5 to 50 years old, will be enrolled and grouped according to their infection status. S. haematobium and malaria parasites will be detected, demographic and clinical data will be recorded and blood will be collected for hematological as well as for immunological assays. The level of antibody specific to Plasmodium falciparum blood stage and gametocyte antigens will be measured using ELISA. PBMC will be isolated for phenotyping of different T cell subsets ex vivo by flow cytometry and for culture and cytokine response assessment. DISCUSSION: We will provide a comprehensive picture of the interaction between schistosomes and malaria parasites which co-localize in peripheral blood. We will test the hypothesis that schistosome infection has an impact on specific humoral as well as on cellular immune responses to malaria antigens. PMID- 25120948 TI - Peroxidase activity in scutella of maize in association with anatomical changes during germination and grain storage. AB - The embryo of the maize grain (Zea mays L.) is separated from the starchy endosperm by a fibrous structure, which is called the fibrous layer (FL). Using histochemical staining, it was determined that the FL is composed of collapsed cellular layers that contain phenols, neutral lipids, and 1,3-beta-glucan. Due to its composition, the FL prevents free diffusion and separates the embryo from the endosperm during germination. Twenty-four hours after imbibition, the scutellum epidermis initiated a series of asynchronous spatial modifications, including cell growth, the perforation of cell walls, increased peroxidase activity in the apoplastic space, and elevated levels of superoxide, phenols, and other components that interact with the fibrous layer, enabling its transformation in addition to the free flow between compartments. During storage at high relative humidity levels, which leads to fast or slow deterioration depending on the temperature, the activity of phenol peroxidase in the scutellum was associated with a loss of vigor and reduced germination capacity when compared with low temperature and low relative humidity conditions. Such deterioration is associated with alterations in autofluorescent emissions from endogenous compounds in the scutellum, indicating changes in the microenvironment or in the differential proportions of epidermal and FL components. PMID- 25120950 TI - Pectoral nerves (PECS) and intercostal nerve block for cardiac resynchronization therapy device implantation. AB - A 71-year-old man was scheduled to undergo cardiac resynchronization therapy device (CRTD) implantation. He was combined with severe chronic heart failure due to ischemic heart disease. NYHA class was 3 to 4 and electrocardiogram showed non sustained ventricular. Ejection fraction was about 20% revealed by transthoracic echocardiogram. He was also on several anticoagulation medications. We planned to implant the device under the greater pectoral muscle. As general anesthesia was considered risky, monitored anesthesia care utilizing peripheral nerve block and slight sedation was scheduled. Pectoral nerves (PECS) block and intercostal block was performed under ultrasonography with ropivacaine. For sedation during the procedure, continuous infusion of dexmedetomidine without a loading dose was performed. The procedure lasted about 3 hours, but the patient showed no pain or restlessness. Combination of PECS block and intercostal block may provide effective analgesia for CRTD implantation. PMID- 25120949 TI - Analyzing the efficiency of small and medium-sized enterprises of a national technology innovation research and development program. AB - This study analyzes the efficiency of small and medium-sized enterprises (SMEs) of a national technology innovation research and development (R&D) program. In particular, an empirical analysis is presented that aims to answer the following question: "Is there a difference in the efficiency between R&D collaboration types and between government R&D subsidy sizes?" Methodologically, the efficiency of a government-sponsored R&D project (i.e., GSP) is measured by Data Envelopment Analysis (DEA), and a nonparametric analysis of variance method, the Kruskal Wallis (KW) test is adopted to see if the efficiency differences between R&D collaboration types and between government R&D subsidy sizes are statistically significant. This study's major findings are as follows. First, contrary to our hypothesis, when we controlled the influence of government R&D subsidy size, there was no statistically significant difference in the efficiency between R&D collaboration types. However, the R&D collaboration type, "SME-University Laboratory" Joint-Venture was superior to the others, achieving the largest median and the smallest interquartile range of DEA efficiency scores. Second, the differences in the efficiency were statistically significant between government R&D subsidy sizes, and the phenomenon of diseconomies of scale was identified on the whole. As the government R&D subsidy size increases, the central measures of DEA efficiency scores were reduced, but the dispersion measures rather tended to get larger. PMID- 25120952 TI - Corrigendum: glycobiology of neuroblastoma: impact on tumor behavior, prognosis, and therapeutic strategies. PMID- 25120951 TI - Yttrium-90 radioembolization of hepatic metastases from colorectal cancer. AB - Liver metastases from colorectal cancer (CRC) result in substantial morbidity and mortality. The primary treatment is systemic chemotherapy, and in selected patients, surgical resection; however, for patients who are not surgical candidates and/or fail systemic chemotherapy, liver-directed therapies are increasingly being utilized. Yttrium-90 (Y-90) microsphere therapy, also known as selective internal radiation therapy (SIRT) or radioembolization, has proven to be effective in terms of extending time to progression of disease and also providing survival benefit. This review focuses on the use of Y-90 microsphere therapy in the treatment of liver metastases from CRC, including a comprehensive review of published clinical trials and prospective studies conducted thus far. We review the methodology, outcomes, and side effects of Y-90 microsphere therapy for metastatic CRC. PMID- 25120954 TI - X-linked inhibitor of apoptosis protein - a critical death resistance regulator and therapeutic target for personalized cancer therapy. AB - Defects in apoptosis regulation are one main cause of cancer development and may result from overexpression of anti-apoptotic proteins such as inhibitor of apoptosis proteins (IAPs). IAPs are cell death regulators that, among other functions, bind caspases, and interfere with apoptotic signaling via death receptors or intrinsic cell death pathways. All IAPs share one to three common structures, the so called baculovirus-IAP-repeat (BIR)-domains that allow them to bind caspases and other proteins. X-linked inhibitor of apoptosis protein (XIAP) is the most potent and best-defined anti-apoptotic IAP family member that directly neutralizes caspase-9 via its BIR3 domain and the effector caspases-3 and -7 via its BIR2 domain. A natural inhibitor of XIAP is SMAC/Diablo, which is released from mitochondria in apoptotic cells and displaces bound caspases from the BIR2/BIR3 domains of XIAP thereby reactivating cell death execution. The central apoptosis-inhibitory function of XIAP and its overexpression in many different types of advanced cancers have led to significant efforts to identify therapeutics that neutralize its anti-apoptotic effect. Most of these drugs are chemical derivatives of the N-terminal part of SMAC/Diablo. These "SMAC-mimetics" either specifically induce apoptosis in cancer cells or act as drug-sensitizers. Several "SMAC-mimetics" are currently tested by the pharmaceutical industry in Phase I and Phase II trials. In this review, we will discuss recent advances in understanding the function of IAPs in normal and malignant cells and focus on approaches to specifically neutralize XIAP in cancer cells. PMID- 25120955 TI - Side effects of yttrium-90 radioembolization. AB - Limited therapeutic options are available for hepatic malignancies. Image guided targeted therapies have established their role in management of primary and secondary hepatic malignancies. Radioembolization with yttrium-90 ((90)Y) microspheres is safe and efficacious for treatment of hepatic malignancies. The tumoricidal effect of radioembolization is predominantly due to radioactivity and not ischemia. This article will present a comprehensive review of the side effects that have been associated with radioembolization using (90)Y microspheres. Some of the described side effects are associated with all transarterial procedures. Side effects specific to radioembolization will also be discussed in detail. Methods to decrease the incidence of these potential side effects will also be discussed. PMID- 25120956 TI - Advancements toward a systems level understanding of the human oral microbiome. AB - Oral microbes represent one of the most well studied microbial communities owing to the fact that they are a fundamental part of human development influencing health and disease, an easily accessible human microbiome, a highly structured and remarkably resilient biofilm as well as a model of bacteria-bacteria and bacteria-host interactions. In the last 80 years since oral plaque was first characterized for its functionally stable physiological properties such as the highly repeatable rapid pH decrease upon carbohydrate addition and subsequent recovery phase, the fundamental approaches to study the oral microbiome have cycled back and forth between community level investigations and characterizing individual model isolates. Since that time, many individual species have been well characterized and the development of the early plaque community, which involves many cell-cell binding interactions, has been carefully described. With high throughput sequencing enabling the enormous diversity of the oral cavity to be realized, a number of new challenges to progress were revealed. The large number of uncultivated oral species, the high interpersonal variability of taxonomic carriage and the possibility of multiple pathways to dysbiosis pose as major hurdles to obtain a systems level understanding from the community to the gene level. It is now possible however to start connecting the insights gained from single species with community wide approaches. This review will discuss some of the recent insights into the oral microbiome at a fundamental level, existing knowledge gaps, as well as challenges that have surfaced and the approaches to address them. PMID- 25120953 TI - Genomic Analysis as the First Step toward Personalized Treatment in Renal Cell Carcinoma. AB - Drug resistance mechanisms in renal cell carcinoma (RCC) still remain elusive. Although most patients initially respond to targeted therapy, acquired resistance can still develop eventually. Most of the patients suffer from intrinsic (genetic) resistance as well, suggesting that there is substantial need to broaden our knowledge in the field of RCC genetics. As molecular abnormalities occur for various reasons, ranging from single nucleotide polymorphisms to large chromosomal defects, conducting whole-genome association studies using high throughput techniques seems inevitable. In principle, data obtained via genome wide research should be continued and performed on a large scale for the purposes of drug development and identification of biological pathways underlying cancerogenesis. Genetic alterations are mostly unique for each histological RCC subtype. According to recently published data, RCC is a highly heterogeneous tumor. In this paper, the authors discuss the following: (1) current state-of-the art knowledge on the potential biomarkers of RCC subtypes; (2) significant obstacles encountered in the translational research on RCC; and (3) recent molecular findings that may have a crucial impact on future therapeutic approaches. PMID- 25120959 TI - Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench. AB - High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases. PMID- 25120961 TI - Morphological study of dendritic cells in human cervix by zinc iodide osmium method. AB - BACKGROUND: Dendritic cells (DCs) are a heterogeneous population of antigen presenting cells that have been identified in several tissues including the female reproductive organs. The aim of the present study is to demonstrate the morphological differences of dendritic cells in normal human exocervix using the Zinc Iodide Osmium (ZIO) procedure. MATERIALS AND METHODS: Normal cervical tissues obtained from nine patients who underwent abdominal hysterectomies for various ailments were processed for histochemical study. Six microns thick serial sections were taken and viewed under a light microscope. The diameters of the cells were measured under a magnification of 40x using the Cellsens image analysing software and analysed using SPSS version 16. RESULTS AND CONCLUSION: In the normal human exocervix, a greater density of ZIO-positive DCs was noted in the epithelium and subepithelium and their distribution was not uniform. In some areas of epithelium, the ZIO-positive cells in the basal layer showed a typical dendritic morphology, while the cells in the intermediate and superficial layers were nondendritic polygonal cells. Intraepithelial capillaries were noted, which were surrounded by ZIO-positive nondendritic polygonal cells. There was significant difference in the mean diameters of typical DCs (8.61+/-1.86 MUm) and nondendritic polygonal cells (10.97+/-1.93 MUm). In the subepithelium the DCs had typical morphology and their distribution varied. ZIO positive DCs were noted in the epithelium and cervical glands of endocervix also. In conclusion, the human cervix has different subsets of ZIO positive DCs with varied distribution. Their functional role has yet to be defined. PMID- 25120962 TI - Evaluation of Fetal Central Nervous System Anomalies by Ultrasound and Its Anatomical Co-relation. AB - INTRODUCTION: Central nervous system anomalies are often severe and are the most common indications for therapeutic abortions. Ultrasound examination helps to identify and evaluate them well before birth. OBJECTIVES: Present study was undertaken to evaluate the incidence of central nervous system anomalies in utero by ultrasound and to confirm them by autopsy or postnatal examination. METHOD: Ultrasound screening of 7485 pregnant women was performed. Pregnancy with ultrasound findings of central nervous system anomalies were followed up. Prenatal ultrasound findings were confirmed by autopsy in cases of therapeutic abortions and fetal losses. In case of live birth postnatal findings were noted. RESULTS: Ultrasound detected central nervous system malformations in 24 fetuses. Ultrasound findings were matching in 83% on autopsy. Autopsy and postnatal findings together were matching with ultrasound in 85.7%. Two cases had additional minor findings on autopsy. CONCLUSION: The incidence of central nervous system malformations on ultrasound was 0.31%. Autopsy and postnatal examination showed high degree of correlation with ultrasound findings. PMID- 25120958 TI - Pathogenesis of cerebral malaria--inflammation and cytoadherence. AB - Despite decades of research on cerebral malaria (CM) there is still a paucity of knowledge about what actual causes CM and why certain people develop it. Although sequestration of P. falciparum infected red blood cells has been linked to pathology, it is still not clear if this is directly or solely responsible for this clinical syndrome. Recent data have suggested that a combination of parasite variant types, mainly defined by the variant surface antigen, P. falciparum erythrocyte membrane protein 1 (PfEMP1), its receptors, coagulation and host endothelial cell activation (or inflammation) are equally important. This makes CM a multi-factorial disease and a challenge to unravel its causes to decrease its detrimental impact. PMID- 25120957 TI - Staphylococcus aureus Small Colony Variants (SCVs): a road map for the metabolic pathways involved in persistent infections. AB - Persistent and relapsing infections, despite apparently adequate antibiotic therapy, occur frequently with many pathogens, but it is an especially prominent problem with Staphylococcus aureus infections. For the purposes of this review, persistence will encompass both of the concepts of long term survival within the host, including colonization, and the concept of resisting antibiotic therapy even when susceptible in the clinical microbiology laboratory. Over the past two decades, the mechanisms whereby bacteria achieve persistence are slowly being unraveled. S. aureus small colony variants (SCVs) are linked to chronic, recurrent, and antibiotic-resistant infections, and the study of SCVs has contributed significantly to understanding of persistence. In our earlier work, defects in electron transport and thymidylate biosynthesis were linked to the development of the SCV phenotype (reviewed in 2006), thus this work will be discussed only briefly. Since 2006, it has been found that persistent organisms including SCVs are part of the normal life cycle of bacteria, and often they arise in response to harsh conditions, e.g., antibiotics, starvation, host cationic peptides. Many of the changes found in these early SCVs have provided a map for the discovery mechanisms (pathways) for the development of persistent organisms. For example, changes in RNA processing, stringent response, toxin antitoxin, ribosome protein L6 (RplF), and cold shock protein B (CspB) found in SCVs are also found in other persisters. In addition, many classic persister organisms also show slow growth, hence SCVs. Recent work on S. aureus USA300 has elucidated the impact of aerobic expression of arginine deiminase genes on its ability to chronically colonize the skin and survive in abscesses. S. aureus SCVs also express arginine deiminase genes aerobically as well. Thus, many pathways found activated in electron transport type of SCVs are also increased in persisters that have intact electron transport. Many of these changes in metabolism result in slow growth; hence, small colonies are formed. Another common theme is that slow growth is also associated with reduced expression of virulence factors and enhanced uptake/survival within host cells. These adaptations to survive within the host are rooted in responses that were required for organisms to survive in a harsh environment long before they were mammals on the earth. PMID- 25120964 TI - Anomalous Branching Pattern of the Popliteal Artery (PA): A Case Report. AB - The Popliteal Artery (PA), which is the continuation of the Femoral artery, crosses the popliteal fossa at the distal border of popliteus; it divides into the Anterior and Posterior Tibial arteries. The Posterior Tibial Artery (PTA) divides into terminal branches proximal to popliteus, in which case the Anterior Tibial Artery (ATA) sometimes descends anterior to the muscle. Either the Anterior tibial or the PTA may be reduced or increased in size. The dorsalis pedis artery (DPA) is the continuation of the ATA, distal to the ankle. It passes to the proximal end of the first intermetatarsal space, to complete the plantar arch, and provides the first plantar metatarsal artery. In the present case the PA bifurcates into two terminal branches at a higher level than the normal. The ATA was hypo plastic and entered the anterior crural region in front of the popliteus muscle and finally terminated above the knee joint. Further the PTA was also hypo plastic giving off a hyperplastic PL which pierced the interosseous membrane and on entering the dorsum of the foot, it prolonged as the DPA. The rest of the PTA continued its course distally and divided into its usual branches, the medial and lateral planter arteries. Awareness of these variations in the vascular branching patterns of the lower limb, acts as a guide during femero distal bypass grafting procedures and surgical and percutaneous vascular reconstructions. PMID- 25120960 TI - High-throughput screening of tick-borne pathogens in Europe. AB - Due to increased travel, climatic, and environmental changes, the incidence of tick-borne disease in both humans and animals is increasing throughout Europe. Therefore, extended surveillance tools are desirable. To accurately screen tick borne pathogens (TBPs), a large scale epidemiological study was conducted on 7050 Ixodes ricinus nymphs collected from France, Denmark, and the Netherlands using a powerful new high-throughput approach. This advanced methodology permitted the simultaneous detection of 25 bacterial, and 12 parasitic species (including; Borrelia, Anaplasma, Ehrlichia, Rickettsia, Bartonella, Candidatus Neoehrlichia, Coxiella, Francisella, Babesia, and Theileria genus) across 94 samples. We successfully determined the prevalence of expected (Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Rickettsia helvetica, Candidatus Neoehrlichia mikurensis, Babesia divergens, Babesia venatorum), unexpected (Borrelia miyamotoi), and rare (Bartonella henselae) pathogens in the three European countries. Moreover we detected Borrelia spielmanii, Borrelia miyamotoi, Babesia divergens, and Babesia venatorum for the first time in Danish ticks. This surveillance method represents a major improvement in epidemiological studies, able to facilitate comprehensive testing of TBPs, and which can also be customized to monitor emerging diseases. PMID- 25120963 TI - Radiographical study showing asymmetry in the surface area of carpal bones in malnourished children. AB - BACKGROUND: Protein energy malnutrition, a major health and nutritional problem in India, leads to retardation in bone maturity and eventually physical growth. Many studies have been done on ossification centers of hand bones for estimation of skeletal maturation and to diagnose malnutrition but very few studies have been done so far to see effect of protein energy malnutrition on surface area of carpal bones. AIMS AND OBJECTIVES: The surface areas of carpal bones on radiographs on both sides were calculated, analysed and compared in protein energy malnutrition (PEM) cases and healthy controls upto five years of age to see the variability among study groups. MATERIALS AND METHODS: The study was conducted in Department of Paediatrics, Radiodiagnosis and Anatomy of S.N. Medical College, Agra, India consisting of 68 PEM cases and 68 controls of either sex upto five years of age. Radiography of wrist done and surface areas of carpal bones were calculated by using millimeter Graph Transparency paper by Hit method and data were evaluated for significance by using t-test. RESULT: The surface areas of capitate, hamate and triquetral bones of both hands were reduced in PEM children of all grades as compared to healthy controls. The surface areas of these carpal bones were much reduced in grade 2 and grade 3 PEM cases as compared to healthy controls and grade 1 PEM cases. Asymmetry in surface areas of capitate and hamate bones were ascertained in healthy controls and grade 1 PEM cases but due to delay in appearance of ossification centers and reduced surface areas of these bones, asymmetry could not be ascertained in grade 2 and grade 3 malnutrition children. CONCLUSION: The surface areas of capitate, hamate and triquetral bones on both sides were reduced in grade 2 and grade 3 PEM cases as compared to controls. Asymmetry in surface area of carpal bones was ascertained in healthy controls and grade 1 PEM cases. PMID- 25120966 TI - Foot index in right footed adults. PMID- 25120965 TI - Anatomical variation: median nerve formation - a case vignette. AB - Variations in the arrangement and distribution of brachial plexus and its branches in the infraclavicular part are common and have been reported by several investigators since the 19th century. These variations are significant for the neurologists, surgeons, anesthetists and the anatomists. During routine anatomical dissection of the right axilla and infraclavicular region of a 45-year old male cadaver, the medial root of the median nerve was found to receive a supplementary branch from the medial aspect of the terminal portion of the lateral cord of brachial plexus and the branch was passing infront of the axillary artery from lateral to medial side. The median nerve was formed by joining of the lateral and medial roots from the lateral and medial cords of brachial plexus, infront of brachial artery, lower down, at the junction of upper one-third and lower two-third of the arm, instead in the axilla. This variation could be one of the cause of pressure symptom which occurs on the axillary artery and also the injury which occurs on the lateral cord or upstream to the lateral cord, which may sometimes lead to an unexpected presentation of weakness of forearm flexors and thenar muscles. PMID- 25120967 TI - Study of cardiovascular reactivity to mental stress in different phases of menstrual cycle. AB - BACKGROUND: It is a well known fact that normally female sex hormone levels fluctuate during the menstrual cycle. The presence of receptors for these hormones on both heart and blood vessels may also hint at variations in physiological functions during menstrual cycle. So this study was an attempt to determine whether the follicular and luteal phases of menstrual cycle are characterized by variations in cardiovascular parameters in the resting state and also examine changes in cardiovascular reactivity to mental stress challenge during both the phases of menstrual cycle. METHODOLOGY: Thirty healthy females in the age group of 18-25 years with regular menstrual cycles fulfilling the inclusion criteria were examined for cardiovascular parameters (heart rate and blood pressures) at rest and their reactivity to mental stress during the follicular and luteal phase and were compared by using paired t-test. A p-value of <0.05 was considered as statistically significant. RESULTS: The women included in the study produced the well known reactivity to mental stress, in terms of blood pressure and heart rate increases, but the two phases of menstrual cycle were indistinguishable in so far as reactivity patterns were considered. The resting values of these cardiovascular parameters were also alike during the two phases. CONCLUSION: We were unable to unearth any differences in resting and reactivity values of cardiovascular parameters during the course of a normal menstrual cycle. This shows that stress reactivity variations during different phases of menstrual cycle may not be due to variations in hormonal levels per se, but due to collusion of hormonal variations and unknown genetic influences. PMID- 25120968 TI - Alteration of Interferon Gamma (IFN-gamma) in Human Plasma with Graded Physical Activity. AB - INTRODUCTION: Practice of regular exercise is beneficial for health. Physical exercises have been demonstrated to alter levels of the cytokine interferon Gamma in plasma. IFN-gamma is known to be an anti-inflammatory cytokine. MATERIALS AND METHODS: We assessed the effect of single bout of moderate exercise and a single bout of strenuous exercise and one month of regular moderate exercise on plasma IFN-gamma. The study consisted of 18 healthy volunteers (10 males and 8 females) with the mean age, 20.94 years, range, 18-25 years. The exercise regime adopted is the standardized 10m Shuttle Walk Test regime. IFN-gamma was estimated using the Sandwich ELISA technique. The reagent kit was obtained from Duoset ELISA Development System of R & D Systems Europe Ltd. The readings were taken at 450nm using Organon Teknika Reader 230S. STATISTICAL METHODS: Friedman test has been used for analysing IFN-gamma values. RESULTS: Mean and SD values of IFN-gamma (in picograms per ml) for baseline (no exercise) was: 54.56 +/- 28.54 (log transformation: 1.68+/-0.23), for acute moderate exercise: 28.94 +/- 38.46 (log transformation: 1.34 +/- 0.24), for acute strenuous exercise: 20.06 +/- 16.96 (log transformation: 1.18 +/-0.33) and after one month of regular moderate exercise: 106.33 +/- 21.51 (log transformation: 2.02 +/- 0.09). The change in IFN gamma levels showed significant difference between; a) baseline and moderate exercise, b) baseline and strenuous exercise, c) moderate and strenuous exercise, d) strenuous exercise and end of one month of regular moderate exercise, e) baseline and end of one month of regular moderate exercise, f) moderate exercise and end of one month of regular moderate exercise. IFN-gamma showed overall significance between different grades of exercise (p < 0.05). CONCLUSION: Plasma IFN-gamma decreases with one bout of acute moderate exercise, it decreases further with one bout of acute strenuous exercise and increases at end of one month of regular moderate exercise, which is more than baseline value. This shows that regular moderate exercise has beneficial effects on health by way of increasing plasma IFN-gamma level. PMID- 25120969 TI - Effect of age and Blood Pressure on Surrogate Markers of Atherosclerosis in Patients with Type 2 Diabetes Mellitus. AB - BACKGROUND: Increased arterial stiffness may be an important path- way linking diabetes mellitus to increased cardiovascular risk. AIM: The study was conducted to assess the surrogate markers of arterial stiffness in patients with Type 2 diabetes mellitus (T2DM), and compare with age-matched hypertensive and healthy controls. Also the effect of age and blood pressure on these markers was evaluated. SETTINGS AND DESIGN: This cross-sectional study was carried out at a tertiary care hospital in West India. METHODS: After a detailed medical history and anthropometric evaluation, all the participants were subjected to measurements of Arterial Stiffness Index (ASI), Pulse Wave Velocity (PWV), and Augmentation Index (AIx) using a non-invasive oscillometric method. The four study groups consisted of patients with T2DM (>5 years) along with hypertension, newly diagnosed patients with T2DM (<2years) without hypertension, hypertensive controls, and healthy controls. RESULTS: PWV, ASI, AIx were elevated in patients with T2DM compared to healthy controls (p<0.05). Patients with T2DM above 60 years had higher carotid-femoral PWV, ASI and AIx than those below 60 years (p<0.05). ASI and AIx were significantly increased in patients with T2DM with hypertension having systolic BP > 140 mmHg compared to those with systolic BP < 140 mmHg. A very strong correlation between PWV and AIx in patients with T2DM and hypertensive controls was observed. CONCLUSION: This study reveals that markers of arterial stiffness (PWV, ASI, AIx) were increased significantly in patients with T2DM compared to healthy controls. Age and systolic blood pressure had significant influence on these markers. Thus, oscillometric markers have potential utility in identifying subclinical atherosclerosis in patients with T2DM. PMID- 25120970 TI - Comparison of cognitive functions between male and female medical students: a pilot study. AB - BACKGROUND: There are gender differences in cognitive abilities. The major enigma is whether males or females perform better in various cognitive tasks. The reports were found to be contradictory. Studies have shown that oestrogen and testosterone accentuate cognitive functions. But the effects of progesterone on cognitive functions are still contradictory. OBJECTIVE: To assess and compare the cognitive functions between male and female students. METHODS: This study was conducted on healthy male (n=21) and female (n=21) volunteers who were aged between 19-37 years. Cognitive functions which were assessed in males (one time) and females (two times: during preovulatory and postovulatory phases of the menstrual cycle) were attentional: visual reaction time (VRT) and Go/No-Go VRT; perceptual: fast counting (FC), executive: Erisken Flanker Test (EFT) and Stroop Test (ST), and working memory. Data were compared by using Mann-Whitney U-test. RESULTS: Cognitive functions in female preovulatory phase were comparable to male cognitive functions. In addition, the female postovulatory phase cognitive functions were also similar to those of males in all the tasks, except those seen in VRT and ST. Male performed better than females in VRT (M: 331.66 ms, IQR: 286.99-375.33 vs. M: 367.8 ms, IQR: 340.66-435.66; p=0.05). However, in ST, females showed higher accuracies in reading colour interferences than males (M: 100%, IQR: 95.12-100 vs. M: 95.24%, IQR: 86.36-100; p=0.04). In addition, males showed trend of a poorer performance than females in Go/No-Go VRT, ST colour reading normal time and interference time and in working-memory time. CONCLUSION: Male cognitive functions were comparable to female preovulatory phase cognitive functions. However, females, during postovulatory phase of their cycle, may have advantages in executive tasks (Stroop test) and disadvantages in attentional tasks (VRT), as compared to males. PMID- 25120971 TI - Brainstem Auditory Evoked Potentials (BAEP)- A Pilot Study Conducted on Young Healthy Adults from Central India. AB - OBJECTIVE: To Evaluate I, II, III, IV, V wave latencies and I-III, III-V, I-V inter-peak latencies and V/I wave amplitude ratio in Normal subjects in Central India. METHODS: We recorded BAEP from 50 healthy normal subjects from the community of same sex and geographical setup. The absolute, interpeak and wave V/I amplitude ratio were measurement and recording was done using RMS EMG EP MARK II machine manufactured by RMS recorders and Medicare system, Chandigarh. RESULT: Absolute, interpeak and wave V/I amplitude ratio were measured in normal subjects and compared with other previous studies. CONCLUSION: This study was conducted as exploratory pilot study only on male healthy controls. Since, the study conducted in different regions, there are some differences in the latencies and interpeak latencies and amplitude ratio but they are within range, so reference range of this study can be used for future studies in this Wardha region of Central India. PMID- 25120972 TI - Study of Cholesteryl Ester Transfer Protein (CETP) I405v Genotype and Its Association with Lipid Fractions in Myocardial Infarction Patients: A Case Control Study. AB - OBJECTIVES: We determine the significant relation of HDL cholesterol and total cholesterol/HDL cholesterol between CETP I405V genotypes and activity of CETP. CETP is an essential for transfer of cholesterol ester to the liver from peripheral tissues which facilitating its transfer to TG rich VLDL. Reduction activity of CETP I405V may associate with genotypes of CETP I405V. This study is undertaken to assess the presence and impact of CETP I405V genotype in our population. MATERIALS AND METHODS: In this study 100 acute myocardial infarction patients and 100 normal age & sex matched healthy individuals were included. Serum Lipid profile was estimated by using universal standard methods whereas CETP I405V genotype was studied by ARMS PCR. RESULT: There is presence of CETP 405Val genotype both in patient as well as in control group. RESULTs show that HDL cholesterol (p<0.0001) and ratio of total cholesterol/HDL cholesterol are significantly (p<0.0043) associated with Val/Val genotype. In addition to that the CETP I405V genotype is associated with inhibition of CETP activity with higher HDL-C level and decreased total cholesterol/HDL cholesterol ratio. CONCLUSION: Our results show that the CETP I405V genotypes are very much significantly determinant of HDL cholesterol in patients with CHD. PMID- 25120973 TI - Validation of Method Performance of pH, PCO2, PO2, Na(+), K(+) of Cobas b121 ABG Analyser. AB - INTRODUCTION: The introduction of a new method or new analyser is a common occurrence in clinical biochemistry laboratory. Blood gas measurements and electrolytes are often performed in Point-of-Care (POC) settings. When a new POC analyser is obtained, the performance of the analyser should be evaluated by comparison to the measurements with the reference analyser in the laboratory. OBJECTIVES: Evaluation of method performance of pH, PCO2, PO2, Na(+), K(+) of cobas b121 ABG analyser. MATERIALS & METHODS: The evaluation of method performance of pH, PO2, PCO2, Na(+), K(+) of cobas b121 ABG analyser was done by comparing the results of 50 patient samples run on cobas b121 with the results obtained from Rapid lab values (reference analyser). Correlation coefficient was calculated from the results obtained from both the analysers. Precision was calculated by running biorad ABG control samples. RESULTS: The correlation coefficient values obtained for parameters were close to 1.0 indicating good correlation. The CV obtained for all the parameters were less than 5 indicating good precision. CONCLUSION: The new ABG analyser, Cobas b121 correlated well with the reference ABG analyser (Rapid Lab) and could be used to run on patient samples. PMID- 25120974 TI - Correlation of Plasma Lipid Profile with Salivary Oxidative Stress Markers in Type II Diabetes Mellitus Patients. AB - INTRODUCTION: Diabetes is known to be associated with greater production of reactive oxygen species (ROS) like malondialdehyde (MDA) and decreased antioxidants like total thiols and its estimation in plasma is used in monitoring the redox status. The aim of this study was to analyse the association between plasma lipid profile parameters like HDL and LDL with salivary MDA and thiols in diabetic patients. MATERIALS AND METHODS: Sixty subjects between the age group 35 70 years who were diagnosed with type II diabetes mellitus based on fasting blood glucose and glycated haemoglobin levels who attended the dental OPD at Kasturba Medical College and Hospital, Manipal consented to participate in this study. Plasma glucose, HDL and LDL were estimated in Cobas autoanalyser by hexokinase method, homogenous enzymatic colorimetric assay and Friedwald's formula respectively. Assessment of glycated hemoglobin was by ion exchange chromatography, MDA by thiobarbituric acid as a substrate and thiols by Ellmann's manual method in plasma and saliva. RESULTS: The association of plasma LDL with salivary MDA was found to be positive and significant and that with salivary thiols was negative and significant. Also, the association of plasma HDL with salivary MDA was found to be negative and significant and that with salivary thiols was positive and significant. CONCLUSION: RESULTS indicate the potential of saliva as a tool to monitor prognosis of diabetes. PMID- 25120975 TI - Association of high sensitivity C-reactive protein with the components of metabolic syndrome in diabetic and non-diabetic individuals. AB - BACKGROUND AND OBJECTIVES: High sensitivity C-reactive protein (hsCRP) has been associated with metabolic syndrome (MetS) and its components. Several studies have suggested hsCRP to be used as a marker for the primary prevention of cardiovascular diseases. So, we aimed to evaluate the association between hsCRP levels and the components of MetS in diabetic and non-diabetic population. MATERIALS AND METHODS: Type II diabetic patients (T2DM) (n= 121) and healthy controls (n= 121) were enrolled for the study. Anthropometric measurements were taken along with blood pressure from the arm. Ten ml of blood was collected after overnight fasting for the measurement of lipid profile, hsCRP, C-peptide and glucose levels. Insulin resistance (HOMA2-IR) was estimated by HOMA2 calculator utilizing glucose and C-peptide values. All participants were classified into two groups on the basis of the presence or absence of MetS. Data were analysed through SPSS 14 software. RESULTS: hsCRP, C-peptide and HOMA2-IR were significantly higher in T2DM subjects when compared with controls. As the number of the components of MetS increased, there was a linear increase in hsCRP levels in whole study population (p trend <.001), diabetic subjects (p trend <.001), as well as in controls (p trend <.001). HOMA2-IR and hsCRP levels were found to be better than LDL cholesterol and waist circumference for predicting the presence of MetS. CONCLUSION: hsCRP was found to be better than LDL cholesterol and waist circumference for the prediction of MetS. Hence, hsCRP could be used as a defining marker of MetS in the near future. PMID- 25120976 TI - Emergence of Escherichia coli, Co-Producing NDM-1 and OXA-48 Carbapenemases, in Urinary Isolates, at a Tertiary Care Centre at Central India. AB - OBJECTIVE: To detect genes encoding carbapenem resistance in urinary isolates of Escherichia coli recovered from hospitalized patients in tertiary care centre in Pune, India. METHODS: From Jan 2012 to Dec 2012, a total of 300 consecutive non duplicate (one isolate per patient) clinical isolates of Escherichia coli were recovered from urine cultures of hospitalized patients including hospital acquired infection cases admitted to the medical and surgical intensive care units. Polymerase chain reaction (PCR) assays and sequencing was used to determine the presence of beta-lactamase encoding genes. Conjugation experiments were performed to determine the transferability of beta-lactamase. RESULTS: All the isolates were completely resistant to the second and third generation cephalosporins tested as well as carbapenems. All the isolates showed 100% susceptibility to tigecycline and colistin in vitro. Conjugation experiments demonstrated that blaNDM-1 was transferable via plasmid. All the isolates showed presence of blaNDM-1 and co-association of blaOXA-48 was 25/45(55%) of the isolates. Repetitive element based PCR (REP PCR), Enterobacterial Repetitive Intergenic Consensus (ERIC PCR) and Randomly Amplified Polymorphic DNA (RAPD) revealed a diversity of six clonal types among E.coli isolates. CONCLUSION: Co production of NDM-1with OXA-48 in urinary isolates of E. coli was detected for the first time in India. Transmission of plasmid carrying these resistant genes to other members of Enterobacteriaceae will increase incidence of multidrug resistance. Early detection of these genes will help in prevention and adequate infection control by limiting the spread of these organisms. PMID- 25120977 TI - Comparision of Three Laboratory Tests for Detection of AmpC beta Lactamases in Klebsiella Species and E. Coli. AB - BACKGROUND AND OBJECTIVE: AmpC beta lactamases are one of the important causes of drug resistance in gram negative bacteria. Failure to detect these enzymes in the laboratory has contributed to therapeutic failures but there are till date no standard guideline available. This study was therefore undertaken to evaluate three phenotypic laboratory tests and the inhibitors used in two of the tests to detect AmpC beta lactamases produced by E. coli and Klebsiella species as they are most commonly isolated organisms. METHODS: E. coli and Klebsiella isolates from different clinical samples were tested for ESBLs production as per CLSI guidelines and excluded from the study. The non-ESBLs isolates were then screened for AmpC beta lactamases production, by cefoxitin and then confirmed by three different methods, i.e., Disc Potentiation Test (DPT) , Double Disc Synergy Test (DDST) and Modified Three Dimensional Test (M3DT) which in the absence of molecular methods, was taken as the gold standard. Boronic acid and cloxacillin were used as inhibitory agents in the Disc Potentiation and Double Disc synergy Tests. RESULTS: A total of 2,933 isolates were tested out of which 165 isolates were detected as non ESBLs producers,135 (81.82%) when screened for AmpC beta lactamases based on resistance to cefoxitin were labelled as positive. 30 (18.18%) cefoxitin sensitive isolates were labelled as probably non AmpC producers . M3DT, in addition to detecting all the 135 (100%) cefoxitin resistant isolates, also detected 5 (16.67%) cefoxitin sensitive isolates as AmpC producers. Other phenotypic tests, DPT and DDST with different inhibitors like boronic acid and cloxacillin in different potencies were all found to be less sensitive. The best results among these two methods were obtained with DDST using cloxacillin 500MUg. CONCLUSION: In the absence of recommended guidelines for AmpC detection, the study reports, among the tests performed, M3DT as the best phenotypic method for AmpC confirmation, as it is not only the most sensitive but also specific test for AmpC as it rules out the resistance due to other mechanisms like the porin channel. PMID- 25120978 TI - Clinico-Immunological Profile of Children Infected with HIV Through Vertical Transmission, in Southern India. AB - BACKGROUND: Karnataka, being "High Prevalent State" of southern India, the HIV infection among antenatal women has crossed 1%. There are very few reports available with CD4 count and stage wise clinical spectrum among children. The clinical spectrum among HIV infected infants and children vary in different areas of the world. Hence it is important to know the spectrum of opportunistic infections and their respective CD4 count among HIV infected children of our locality. MATERIALS AND METHODS: The opportunistic infections among 31 paediatric seropositive patients were evaluated. These all patients were classified as per CDC guide lines into stage I, stage II, and stage III based on CD4 counts of > 1000cells/MUl, 500-999 cells/MUl,<500cells/MUl respectively. The opportunistic infections were diagnosed by standard laboratory investigations. Clinical spectrum presented by each stage children was documented. RESULTS: Children in stage I were 5(16.1%),stage II 14(45.1%) and stage III 12(38.7%). Oral candidiasis (29%) was the commonest, followed by recurrent respiratory tract infection (25.8%), tubercular lymphadenitis (16.1%) and chronic diarrhoea (12.9%). CONCLUSION: The present study showed the children with higher CD4 count had few infections and children with lower CD4 count presented with multiple opportunistic infections. This study also showed vertical transmission as the sole mode of transmission. PMID- 25120979 TI - Non-Invasive Diagnosis of Helicobacter pylori: Evaluation of Two Enzyme Immunoassays, Testing Serum IgG and IgA Response in the Anand District of Central Gujarat,India. AB - CONTEXT: Validation of an accurate and less cumbersome noninvasive method to detect current Helicobacter pylori infection is a requisite for any laboratory. OBJECTIVES: The purpose of this study is to corroborate the usefulness of two commercially available kits NovaTec ELISA-A and ELISA-G, in the detection of ongoing H.pylori infection. MATERIALS AND METHODS: Two hundred and twenty eight consecutive serum samples of symptomatic patients who attended the endoscopy unit of "Deep" surgical hospital, Anand, which were collected during the period from 27th February 2008 to 31st august 2011, were studied. The sera were processed and tested for the detection of the H.pylori IgG and IgA antibody by using a solid phase; capture micro well ELISA, procured from Nova Tec immunodiagnostica GmbH Germany. RESULTS: IgG ELISA showed 100% sensitivity and Negative predictive value (NPV), while IgA ELISA was better in terms of specificity (61.4%) and accuracy (63%) as compared to IgG ELISA. We found 7% (16/228) of IgA positive cases with IgG negative response. IgG response was more common in reflux esophagitis patients (OR 1.451, 95%CI-0.850-2.477) and then in gastritis (OR 0.962, 95%CI 0.570-1.621) and duodenitis(OR-0.806, 95%CI-0.112-5.827), while IgA positive response was more common in duodenitis patients (OR-1.383, 95%CI-0.191-9.995) and reflux esophagitis patients (OR 1.289, 95% CI-0.756-2.197) and least in duodenal ulcer patients (OR 0.670, 95%CI-0.222-2.029). CONCLUSION: IgG update is reliable and accurate test and can be expedient as a screening test and thus serve as an alternative to endoscopy. For the purpose of excluding infection with H.pylori, the performance of IgG is moderate (low specificity) but can be improved by conjunctional IgA testing which will offer some additional diagnostic value. PMID- 25120980 TI - Plasmid Profile Analysis and bla VIM Gene Detection of Metalo beta-lactamase (MBL) Producing Pseudomonas aeruginosa Isolates from Clinical Samples. AB - INTRODUCTION: Pseudomonas aeruginosa is a frequent colonizer of hospitalized patients. They are responsible for serious infections such as meningitis, urological infections, septicemia and pneumonia. Carbapenem resistance of Pseudomonas aeruginosa is currently increasingly reported which is often mediated by production of metallo-beta-lactamase (MBL). Multidrug resistant Pseudomonas aeruginosa isolates may involve reduced cell wall permeability, production of chromosomal and plasmid mediated beta lactamases, aminoglycosides modifying enzymes and an active multidrug efflux mechanism. OBJECTIVE: This study is aimed to detect the presence and the nature of plasmids among metallo-beta-lactamase producing Pseudomonas aeruginosa isolates. Also to detect the presence of bla VIM gene from these isolates. MATERIALS AND METHODS: Clinical isolates of Pseudomonas aeruginosa showing the metalo-beta-lactamase enzyme (MBL) production were isolated. The MBL production was confirmed by three different methods. From the MBL producing isolates plasmid extraction was done by alkaline lysis method. Plasmid positive isolates were subjected for blaVIM gene detection by PCR method. RESULTS: Two thousand seventy six clinical samples yielded 316 (15.22%) Pseudomonas aeruginosa isolates, out of which 141 (44.62%) were multidrug resistant. Among them 25 (17.73%) were metallo-beta-lactamase enzyme producers. Plasmids were extracted from 18 out of 25 isolates tested. Five out of 18 isolates were positive for the blaVIM gene detection by the PCR amplification. CONCLUSION: The MBL producers were susceptible to polymyxin /colistin with MIC ranging from 0.5 - 2MUg/ml. Molecular detection of specific genes bla VIM were positive among the carbapenem resistant isolates. PMID- 25120981 TI - Waging war against extended spectrum Beta lactamase and metallobetalactamase producing pathogens- novel adjuvant antimicrobial agent cse1034- an extended hope. AB - Preamble: In the visage of multidrug resistance among gram negative bacilli, we look forward to carbapenem group of drugs as empiric choice in seriously ill patients. However increasing resistance to carbapenems, the last resort, is of growing concern for all. It's high time to look beyond Carbapenems and emphasize on Carbapenem sparers. OBJECTIVE: This study is to find the susceptibility pattern of the novel adjuvant antimicrobial CSE 1034 a combination of Ceftriaxone+sulbactam+disodium edetate for the current ESBL and MBL isolates in a tertiary care centre. MATERIALS AND METHODS: A total of 823 gram negative bacterial isolates were obtained from different clinical specimens during the period of March, 2013 to October, 2013. The overall prevalence of metallobetalactamase producing gram negative organisms was 11 percent (n=91). We included a total of 141 clinical isolates for this study. RESULTS: Among 141 clinical isolates, 50 isolates (35%) were ESBL producers and 91 (65%) were MBL producers. Maximum numbers of ESBL producers were identified in Escherichia coli followed by Klebsiella pneumoniae, Acinetobacter baumannii and Proteus spp. Maximum numbers of MBL producers were identified in Klebsiella pneumoniae followed by Pseudomonas aeruginosa. CSE 1034 (Ceftriaxone+sulbactam+disodium edetate) showed fairly good in-vitro susceptibility for these ESBL and MBL producing isolates. It exhibited 64 % to 100% susceptibility and 18% to 22% intermediate sensitivity to ESBL producing isolates and 42 % to 89 % susceptible and 10 % to 51 % intermediate response to MBL producing isolates. CONCLUSION: With increasing resistance to the commonly prescribed drugs used to treat infections caused by variety of gram negative organisms, Ceftriaxone+sulbactam+disodium edetate, a novel Antibiotic Adjuvant Entity (AAE) may be a promising option. PMID- 25120983 TI - Acanthamoeba detection in the anterior chamber after therapeutic penetrating keratoplasty. AB - Acanthamoeba infection has been recognized in almost all parts of the world. With most of the literature focusing on contact lens related Acanthamoeba keratitis, ophthalmologists may hesitate to diagnose this entity in patients without lenses. We report the case of a patient with Acanthamoeba infection of the anterior chamber, unrelated to contact lens wear, diagnosed by examination of aqueous tap following penetrating therapeutic keratoplasty. PMID- 25120982 TI - Isolation of MRSA, ESBL and AmpC - beta -lactamases from Neonatal Sepsis at a Tertiary Care Hospital. AB - BACKGROUND AND OBJECTIVES: The emergence of methicillin resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamases (ESBLs) in neonatal intensive care unit patients is increasing. This study aims to find out the bacteriological profile in neonatal sepsis and study their antimicrobial susceptibility pattern including detection of MRSA and ESBLs. MATERIALS AND METHODS: This study was conducted for a period of one and a half years from January 2010 to June 2011 in a tertiary care hospital in Chennai. A total of 182 blood samples were collected using sterile precautions. They were processed following standard laboratory protocol. Antibiogram was done using appropriate antibiotics by Kirby-Bauer disc diffusion method. Isolated Staphylococcus aureus were tested for methicillin resistance using Cefoxitin disc (30MUg), ESBL was detected using combined disc method, MIC reduction and Polymerase chain reaction, metallobetalactamases using EDTA and Amp-C beta lactamases using AmpC disc test. C-reactive protein (CRP) was estimated for all the cases. RESULTS: Out of the 182 cases, 110 (60.4%) were culture positive. Fifty five (63.9 %) of early onset sepsis cases had Gram negative bacteria (GNB) and 19 (79.1%) of late onset sepsis cases had Gram positive bacteria. Out of the total pathogens, 31 (28.1%) were Klebsiella pneumoniae and 30 (27%) were Staphylococcus aureus. 17 (56.6 %) of Staphylococcus aureus were found to be MRSA and they were 100% sensitive to Vancomycin. 33 (67.3%) of Enterobacteriaceae were ESBL producers. ESBL isolates were 100% sensitive to Imipenem. Three (6.1%) of Enterobacteriaceae were AmpC producers and 3 (27.2%) of Pseudomonas aeruginosa were MBL producers. CRP was positive in 99 (54.3%) cases, out of which 94 (94.9%) were culture positive. CONCLUSION: Klebsiella spp. and Staphylococcus aureus were the commonest bacteria causing neonatal sepsis in this centre. Multidrug resistance among the isolates was common. Early diagnosis and institution of specific antibiotics after studying the sensitivity pattern will help in reducing neonatal morbidity and mortality and prevent emergence of drug resistant strains. PMID- 25120986 TI - Seroprevalence of Hepatitis B, Hepatitis C and Human Immunodeficiency viruses amongst Injecting Drug Users in Mumbai,India. PMID- 25120984 TI - Multidrug resistant Shigella flexneri : a rare case of septicemia in an infant. AB - Shigellosis is still an important public health problem in developing and under developed countries. It may lead to rare but potentially fatal various extra intestinal complications like septicemia, involvement of CNS, urinary tract and liver especially in young malnourished children. The disease is difficult to prevent as only few bacteria are required for causing infection and there is increasing infection with multi drug resistant strains. A 6-month-old infant developed septicemia caused by multi drug resistant Shigella flexneri during an episode of gastrointestinal infection. The patient was managed in the emergency ward but unfortunately the infant expired. Considering septic shock, blood culture, stool culture and other relevant investigations were done. Stool as well as blood culture yielded Shigella flexneri. The isolates were multidrug resistant. Following is a rare case presentation of Shigella septicemia with severe shock, DIC and convulsions. The case report demonstrates how shigellosis can lead to a rare life threatening complication and hence should be considered as a possibility in septicemia associated with diarrhea and vomiting in infant and young children. PMID- 25120985 TI - Non-pigmented strain of serratia marcescens: an unusual pathogen causing pulmonary infection in a patient with malignancy. AB - Serratia marcescens is a member of the family Enterobacteriaceae. It has emerged in recent years as an opportunistic pathogen of nosocomial infections. Some biotypes of Serratia marcescens produce the non-diffusible red pigment prodigiosin. Though both pigmented and non-pigmented biotypes may be pathogenic for humans, the non-pigmented biotypes are more virulent due to cytotoxin production and presence of plasmids mediating antibiotic resistance. However in India only one study done 31 years back has reported on infections caused by non pigmented strains of Serratia marcescens. We present a case of a patient with squamous cell carcinoma of the left retromolar trigone, soft palate and buccal mucosa, who developed pulmonary infection with non-pigmented strain of Serratia marcescens. According to the available literature, this is the second report on infection with non-pigmented strain of Serratia marcescens from India. It is imperative to accurately detect the non-pigmented biotypes due to their tendency to cause serious and difficult to treat infections. PMID- 25120987 TI - Red Cell Distribution Width and Serum BNP Level Correlation in Diabetic Patients with Cardiac Failure: A Cross - Sectional Study. AB - INTRODUCTION: Red cell distribution width (RDW) is a red cell measurement given by fully automated hematology analyzers. It is a measure of heterogeneity in the size of circulating erythrocytes. Studies have shown that it is a prognostic marker in non - anemic diabetic patients with symptomatic cardiovascular disease but its correlation with cardiac failure in diabetics has not been studied so far. Moreover, studies have also shown that a higher RDW may reflect an underlying inflammatory state. Since Diabetes is a pro inflammatory state there is a possibility that it might have an influence on the RDW values even when there is no cardiac failure, but research data on this aspect is lacking. B-type natriuretic peptide (BNP) is a proven marker for cardiac failure whose values are comparable with echo cardio graphic findings in assessing the left ventricular dysfunction. AIM AND OBJECTIVES: This study aimed to find out the correlation between RDW% and serum BNP levels in Diabetics with heart failure (cases) when compared to those without failure (controls). Further, we compared the RDW % values of the cases with controls. Settings and Design : The study was approved by institutional ethical and research committee. A cross-sectional study was conducted with patients attending the Diabetes clinic of a tertiary care hospital in Chennai, India, during the period of October to December 2013. Hundred known cases of type II Diabetes mellitus attending Diabetes centre of the Hospital, with clinical and Echo cardio graphic features of cardiac failure were included as cases. Hundred age and gender matched diabetics with negative history of cardiovascular disease and with normal Echo cardio graphic features were included as controls. Informed consent was obtained from all the cases and controls. Demographic data and clinical history were gathered from all the cases and controls by using a standardized self - administered questionnaire. Biochemical and hematological parameters which included Fasting and Postprandial blood sugar, Glycosylated hemoglobin, Complete Blood count including RDW and serum BNP were performed for all the cases and controls. STATISTICAL ANALYSIS: RESULTS were tabulated and analysed using SPSS 20.0 version RESULTS: A statistically significant correlation (p<.001) was found between Red cell Distribution Width % and Serum B type Natriuretic Peptide values in the cases. Further, RDW% showed a statistically significant difference between cases and controls. CONCLUSION: RDW% can be used as a screening parameter to identify cardiac failure in Diabetic patients similar to non-diabetic cardiac failure. RDW% values are significantly higher in cases of Diabetes with failure in comparison to uncomplicated Diabetes. PMID- 25120989 TI - Incidental detection microfilaria in subcutaneous breast nodule of lactating female fnac: a rare case report. AB - Filariasis is a major public health problem which is faced in tropical countries like India. Its diagnosis is made by using peripheral blood smears. However, microfilaria has been detected incidentally during FNACs of various lesions, which were done in clinically unsuspected cases. We are reporting here, an uncommon case of filariasis, which caused a nodular, subcutaneous swelling in left breast of a 30 year old lactating female. A nodular subcutaneous swelling can be caused in breast of a lactating female by lactational associated mastitis, but filaria causing a nodular swelling in a lactating breast is a rare presentation. Aspiration of the swelling demonstrated enormous pathogen presence caused by Woucheria bancrofti and the patient responded well to six weeks of daily anti-filarial treatment with diethylcarbamazine citrate. PMID- 25120990 TI - Myxoid leiomyosarcoma of ovary-a rare case report. AB - Primary pure myxoid leiomyosarcoma of the ovary is extremely rare, comprising of only 1% of the ovarian tumours. Patient presented with a mass in the right iliac fossa since three months. Radiological diagnosis of broad ligament fibroid was given. Right salphingo-oophorectomy with enucleation of ischial fossa and wedge biopsy of left ovary was carried out. Based on gross, microscopy and immunohistochemistry a diagnosis of primary myxoid leiomyosarcoma of ovary was made. We report a rare case of primary pure myxoid leiomyosarcoma of the ovary with metastasis to ischial fossa emphasising on reliable prognostic markers. Ovarian leiomyosarcomas are highly aggressive tumours with poor prognosis. PMID- 25120988 TI - Rare case of chest wall schwannoma with destruction of rib, masquerading as a breast mass. AB - Schwannomas are slow growing, benign, nerve sheath tumours of Schwann cell origin. They predominantly involve head, neck and flexor surfaces of upper and lower extremities, while the chest wall is an uncommon location for schwannomas. Schwannomas may rarely cause erosion of adjacent bone. We are reporting a very rare case of a chest wall schwannoma with destruction of rib which occurred in a 35-year-old female patient, which initially presented as a breast mass and was radiologically misinterpreted as a malignant soft tissue tumour. PMID- 25120991 TI - Chondrolipoma of the lower lip: a case report. AB - A chondrolipoma is an extremely rare form of a benign mesenchymal tumour which contains mature fatty tissue and cartilage. We are presenting a case of chondrolipoma of the lower lip which was seen in a 6-year-old girl. Chondrolipomas are rare neoplasms; their terminologies and pathogeneses have been controversial in the past. Chondrolipomas are uncommonly seen in the oral cavity, in children and in females. Hence, we are reporting this present case because rarity of this lesion. PMID- 25120992 TI - Clear cell atypical fibroxantoma: a rare variant of atypical fibroxanthoma and review of the literature. AB - Atypical fibroxanthoma (AFX) is a superficial variant of pleomorphic malignant fibrous histiocytoma. Clear cell atypical fibroxanthoma (CCAFXA) is a rare variant of atypical fibroxanthoma. A 74-year-old male patient presented with a rapidly growing nodule on the shoulder, which had appeared over a 5-months period. Lesion was excised by the plastic surgeon. Microscopic examination showed an ulcerated nodule composed of pleomorphic spindled and polygonal cells with clear or vacuolated cytoplasm. The neoplastic cells were stained positively with CD68 and CD10 and were stained negative with S-100, Melan A, muscle-specific actin, or pan-cytokeratin. Final diagnosis was clear cell atypical fibroxanthoma. CCAFXA should be differentiated from other clear-cell neoplasms of the skin. Best of our knowledge only 11 cases CCAFXA of have been reported in published studies till date. Herein, we reported 12th case in literature of CCAFXA and review of the literature. PMID- 25120993 TI - Primary ovarian mucinous carcinoma with signet ring cells - report of a rare case. AB - Presence of signet ring cells in ovarian neoplasms are commonly encountered in Krukenberg tumours of ovary. Unusual presence in primary ovarian mucinous tumours may create a diagnostic difficulty. To the best of our knowledge only very few such cases have been reported in the literature indicating their rarity. We report a case of primary ovarian mucinous carcinoma with signet ring cells. The purpose of this presentation is to sensitize the pathologists to consider primary mucinous carcinoma as a differential diagnosis in tumours with signet ring cells. PMID- 25120994 TI - Gastrointestinal stromal tumour of small intestine presenting as a mesenteric mass. AB - Gastrointestinal stromal tumors (GISTs) are uncommon tumors; accounts for 0.1% to 3% of all gastrointestinal neoplasm. Most common site of involvement is stomach (60-70 %), small intestine (20-30 %) and rarely at extra-gastrointestinal sites like omentum and mesentery called as extra-gastrointestinal stromal tumor (EGIST). Diagnosis is based on characteristic histological findings and expression of transmembrane receptor tyrosine kinase protein (CD 117) derived from activated c-kit gene. Herein, we report a case of GIST of small intestine presented as mesenteric mass in a 35- year-old female and discuss review of literature. PMID- 25120995 TI - Chordoma Cutis - A Diagnosis not to be Missed. AB - Chordomas are rare midline tumors of the bone usually arising from sacrum, skull bones and spine, close to neuraxis. However an extensive involvement of the soft tissues can simulate a soft tissue subcutaneous tumour of the gluteal region -a presentation called chordoma cutis. Our patient presented with a gluteal mass and a trucut biopsy was done suspecting a soft tissue tumour. The hematoxylin and eosin stained section of the biopsy closely simulated a lipomatous tumour. However, on closer inspection the clear cells were found to have very fine vacuolations.The usual myxoid background and characteristic physaliferous cells seen in chordomas were not seen. Still a differential of chordoma was entertained in view of the site and age of the patient. Immunohistochemistry for cytokeratin and S-100 was performed and both were unambiguously positive. On literature search, we came across a soft tissue tumour called parachordoma which mimics chordoma both morphologically and immunohistochemically and has also been reported in the gluteal region. An MRI was performed which showed the tumour to be arising from the sacrum and secondarily involving the gluteal soft tissues. This case highlights the importance of considering chordoma in the differential diagnosis of gluteal masses with clear cell morphology even in the absence of physaliferous cells and myxoid background before signing them out as lipomatous tumours. PMID- 25120996 TI - A rare presentation of gallbladder carcinoma metastasis. AB - Gallbladder carcinoma is the 5th most common gastrointestinal cancer. Gallbladder cancer preferentially metastasizes to regional lymph nodes and liver parenchyma. Bone metastases from gallbladder carcinoma are rare presentation. We report a case of gallbladder carcinoma with solitary metastasis to femur bone with surrounding soft tissue involvement, mimicking as soft tissue tumour involving bone. PMID- 25120997 TI - Comparative efficacy of two different dosages of intrathecal magnesium sulphate supplementation in subarachnoid block. AB - BACKGROUND: Spinal anaesthesia is the primary anaesthetic technique for many types of surgeries. Adjuncts to the local anaesthetics (LA) used in spinal anaesthesia can exhibit undesirable side-effects like respiratory depression, urinary retention, pruritis, haemodynamic instability and nausea and vomiting, limiting their use. Magnesium when used in therapeutic doses avoids all of these side-effects. MATERIALS AND METHODS: We conducted a randomized double blind study on 90 patients, 30 in each group, scheduled for orthopaedic lower limb surgery under subarachnoid block. Group I: received bupivacaine (0.5%), 12.5 mg + 0.5 ml of preservative free 0.9% normal saline, Group II received bupivacaine (0.5%), 12.5 mg + 0.2 ml (50 mg) of preservative free 25 % magnesium sulphate + 0.3 ml of preservative free 0.9% normal saline Group III: received bupivacaine (0.5%) 12.5 mg + 0.3 ml (75 mg) of 25 % magnesium sulphate + 0.2 ml of preservative free 0.9% normal saline for subarachnoid block. The onset and duration of sensory block, the highest dermatomal level of sensory block, motor block, time to complete motor block recovery and duration of spinal anaesthesia were recorded. STATISTICAL ANALYSIS: ANOVA was applied to determine the significance of difference between different groups. If p-value was significant then Turkey's Post Hoc Multicomparison test was applied. Values of p<0.05 were considered to be statistically significant. RESULTS: The time of maximum sensory block, time of onset of motor block, duration of sensory block, duration of motor block and time of analgesia request were prolonged in patients given magnesium 50mg and 75mg along with local anaesthetic intrathecally. CONCLUSION: N-methyl-D-aspartate (NMDA) receptor antagonist, magnesium when administered intrathecally along with local anaesthetics prolongs the duration of spinal analgesia without adverse effects. PMID- 25120999 TI - Antidepressant effect of ketamine in sub anaesthetic doses in male albino mice. AB - BACKGROUND: Depression is the most common mental disorder in community settings, and is a major cause of disability across the world. Antidepressants such as SSRI (Selective Serotonin Reuptake Inhibitor) and TCA (Tricyclic antidepressants) are used. These drugs affect the adrenergic and serotonergic pathways. These drugs have an unfavorable side effect profile, take longer time to act and are not very effective in resistant cases. Alternate pathways involving the glutamate receptors have also been linked with depression, hence Ketamine an NMDA antagonist was evaluated for the antidepressant effect. AIM: To study the antidepressant effect of ketamine in subanaesthetic doses in male albino mice. STUDY DESIGN, MATERIALS AND METHODS: The study was a randomized controlled animal study done on 30 male albino BALB/c mice divided into five groups with Imipramine (10mg/kg) as the standard drug and Ketamine in varying doses (5, 7.5, 10 mg/kg) as the test drug. The animal model used was the forced swim test. The reduction in immobility time was taken as the index of the antidepressant effect. STATISTICAL ANALYSIS: The data were analysed with the one way ANOVA test using SPSS version 12. RESULTS AND CONCLUSION: The data analysis showed that Ketamine at a dose lower dose of Ketamine (5mg/kg) did not show a significant antidepressant effect in contrast to the higher doses (7.5 and 10mg/kg) which showed significant antidepressant effect ('p' > 0.05). The inference of this study is that Ketamine has significant antidepressant property at variable dose ranges and further studies can be done on these lines. PMID- 25120998 TI - Beneficial effects of nebivolol in comparison with atenolol on safety and tolerability in essential hypertension. AB - INTRODUCTION: Hypertension, "The silent killer" is a multifactorial disorder which is asymptomatic and if left untreated leads to lethal complications. Nebivolol is a third generation beta blocker with additional vasodilating property due to nitric oxide release. AIM: The current study aims to assess efficacy and safety of Nebivolol and compare with Atenolol. METHODS: This was prospective, double blind, comparative controlled clinical study. Total 90 patients were enrolled into study as per selection criteria. Patients were randomized to receive Atenolol and Nebivolol with 45 patients in each group for 12 weeks. RESULTS AND CONCLUSION: The mean reduction diastolic blood pressure in Nebivolol and Atenolol group was 10.77+/-2.60 and 10.05+/-2.83 respectively. The number of patients with adverse effect events was higher in the Atenolol than in the Nebivolol group (36.84% of Atenolol Vs 12.82% of Nebivolol). Thus it can be concluded that, for the same antihypertensive effect, Nebivolol was better tolerated than Atenolol. PMID- 25121000 TI - Comparative study of high dose mono-therapy of amlodipine or telmisartan, and their low dose combination in mild to moderate hypertension. AB - INTRODUCTION: Hypertension is one of the major public health challenges worldwide. Angiotensin receptor blockers (ARBs) and Calcium channel blockers (CCBs) are among the first line antihypertensive drugs. However, optimal treatment strategies in mild to moderate hypertensives who failed to achieve blood pressure (BP) control with low-dose mono-therapy are not well established. This study was done to compare efficacy and safety of high dose mono-therapy of Amlodipine, Telmisartan and their low dose combination in mild to moderate hypertensives who failed to achieve BP control with low dose mono-therapy of either drug. MATERIALS AND METHODS: A total of 96 patients, fulfilling inclusion and exclusion criteria were enrolled in the study after obtaining informed consent. Patients were randomized into three treatment groups i.e. Telmisartan 80 mg, Amlodipine 10 mg and low dose combination of Telmisartan 40 mg +Amlodipine 5 mg once daily for two months. The systolic BP, Diastolic BP, and ADRs were recorded at 0, 2, 4, 8 weeks. RESULTS: In the present study, significant reduction of mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP) was seen in all the three treatment groups. Low dose combination of Amlodipine 5 mg and Telmisartan 40 mg showed statistically significant reduction in SBP as compared to Telmisartan 80 mg mono-therapy and in DBP as compared to Amlodipine 10 mg mono-therapy. Maximum adverse drug reactions (ADRs) were reported in Amlodipine mono-therapy group, like ankle oedema, constipation, headache and fatigue. DISCUSSION AND CONCLUSION: In term of BP control, low-dose combination therapy appears a better therapeutic approach than high-dose mono therapy. PMID- 25121001 TI - Comparative Study of Lithotripsy and PCNL for 11-15 mm Lower Caliceal Calculi In Community Health Hospital. AB - BACKGROUND AND PURPOSE: Percutaneous Nephrolithotomy (PCNL) is not a popular procedure in smaller sized calculi due to its invasive nature, complications and need for anesthesia. Small sized lower caliceal calculi are generally treated by ESWL but have significantly less clearance rate in spite of several sittings. Here we want to study the efficacy and safe of both procedures in 11 to 15 mm lower caliceal calculi. MATERIALS AND METHODS: We present comparative study of lithotripsy and PCNL in 11-15 mm lower caliceal calculi in our hospital. Total 156 patients were studied 78 underwent lithotripsy and 78 underwent PCNL. We compared results in the form of clearance rate, the number of settings needed, hospital stay, need for anesthesia, blood transfusion rate, chest complication, the incidence of sepsis, the need for another procedure, need for stenting in either group. RESULTS: We found a 67.95% clearance rate in SWL group and 97.43% clearance rate in PCNL group. Hospital stay was minimum in SWL group and was 46 hours in PCNL group. The procedure time was 42 minutes in PCNL and it was 114 mins in SWL (considering all settings). The rest of the complications like chest complication, sepsis and bleeding were negligible due to the small size of calculi. CONCLUSION: In a small sized LPC calculi, PCNL is gaining increased popularity due to lower complication and high safety and complete clearance rate. It is wide accepted by society as the patient is totally stone free at the end of the procedure. SWL is less invasive but less effective and has given significant discomfort to patients. PMID- 25121002 TI - Evaluation of the Hepato and Nephron-Protective Effect of a Polyherbal Mixture using Wistar Albino Rats. AB - AIM: A polyherbal formulation prepared from a mixture of leaves of Gongronema latifolia, Ocimum gratissimum and Vernonia amygdalina (GOV) was evaluated for hepato-nephro protective properties against acetaminophen-induced toxicity in Wistar albino rats. MATERIALS AND METHODS: Normal Wistar albino rats were orally treated with different doses of GOV extract (2, 4 and 8 g/kg b. wt), distilled water and some standard hepatoprotective drugs such as Liv 52 and silymarin for 14 days. However, a day prior to the 14th day, 3 g/kg body weight dose of Acetaminophen (APAP) was administered p.o. 1h before GOV and the standard drugs to induce hepatic and renal damage. The normal control was setup which received only distilled water. The serum levels of liver marker enzymes, biochemical analytes, antioxidant enzymes and hematological parameters were monitored. RESULTS: The results showed that pretreatment of experimental animals with a different doses of the polyherbal formulation dose dependently caused a significant (p<=0.05) increase in the levels of most of the measured hematological parameters but significantly (p<=0.05) reduced the levels of MCV and monocytes when compared to the APAP induced toxin control group. Rats pretreated with GOV exhibited significant (p < 0.05) increase in serum levels of ALP, ALT, AST, GGT, LDH, Cholesterol, Triglycerides, Urea and a subsequent decrease in Albumin, Creatine and Total protein when compared to the normal rats. This trend in enzyme and biochemical analytes levels were significantly (p < 0.05) reversed when compared to toxin control group. GOV significantly (p < 0.05) and dose dependently increased the serum, kidney and hepatic CAT, GPx, GSH, GST, SOD and total protein activity in APAP induced damage in rats compared to the toxin control groups. CONCLUSION: The data from this study suggest that the polyherbal formulation possess hepato and nephron-protective potential against acetaminophen induced hepatotoxicity in rats, thus providing scientific rationale for its use in traditional medicine for the treatment of liver diseases. PMID- 25121003 TI - Pharmacotherapy of Bipolar Affective Disorder: A Hospital based Study from Sub Himalayan Valley of Nepal. AB - INTRODUCTION: In Bipolar disorder the mood of the patients fluctuates between depression and mania. The main objective of the study was to find out the commonest mood stabilizers used for the treatment of Bipolar affective disorders in Western Nepal in hospitalized patients in an actual clinical set up. METHODS: This was a cross-sectional study which was conducted between October 2009 and September 2010 at Psychiatric ward at Manipal teaching hospital, Pokhara, Nepal, a tertiary care hospital situated in Western Nepal. The diagnosis of the disease was based on ICD-10 (Tenth revision) Classification of mental and Behavioural disorders, Diagnostic Criteria for Research. We calculated odds ratio and their 95% confidence intervals (95% CI). p< 0.05 was considered as statistically significant. RESULTS: 62.1% of the patients were less than 40 yrs, 56.3% were male, 72.4% were unemployed and 75.9% of the patients were having monthly income <10,000/month. As far as ethnicity is concerned 37.9% of the cases were Brahmin and by occupation 29.9% of the patients were students followed by housewife 25.3%, labour 17.2%, retired 13.8% respectively. Drugs and Psychotherapy [OR 1.4, 95% (CI 0.575, 3.4017)] was prescribed in age <40 years as compared to age>40 yrs. Male patients [OR 7.22, 95% (CI 0.862, 60.499)] and [OR 2.353, 95% (CI 0.857, 6.455)] received drugs by trade names and drugs not from the national drug list of Nepal as compared to females. Monthly income <10,000/month and [OR 2.8, 95% (CI 0.742, 10.56)] tendency of receiving drugs by trade names. Among the mood elevators Sodium valproate was the commonest drug to be prescribed in 51/87(58.6%) patients followed by Lithium in 30/87 (34.5%) cases and Carbamazepine in 6/87 (6.9%) cases. Sodium valproate was prescribed at 1,000 mg/day, Lithium was prescribed at 900 mg/day in and Carbamazepine was prescribed at 800 mg/day. CONCLUSION: Among all the mood elevators Sodium valproate is the commonest drug prescribed for the treatment of bipolar affective disorder, recommended that there is a trend of using newer drugs like sodium valproate rather than the conventional mood stabilizers like Lithium for bipolar affective disorder in Western Development region of Nepal. PMID- 25121004 TI - Garenoxacin in Skin and Skin Structure Infections Sustained due to Road Traffic Accident. AB - Skin and soft tissue infections represent a continuum of symptoms that range from uncomplicated cellulitis to the potentially lethal entity necrotizing fasciitis that is often considered to be microbial invasions of the epidermis, dermis and subcutaneous tissues. Garenoxacin, a newer oral des-fluoroquinolone having potent antimicrobial activity against wide variety of common pathogens involved in skin and skin structure infections (SSTIs), including the resistant strains offer the advantage of broad spectrum of coverage including gram positive, gram negative and anaerobic organisms. This case study indicates the utility of garenoxacin in treating skin and soft tissue infections caused by road traffic accidents. PMID- 25121005 TI - A Population based Study on Alcoholism among Adult Males in a Rural Area, Tamil Nadu, India. AB - BACKGROUND: India's reputation as a country with a culture of abstinence especially in matters regarding alcohol is underserved. There has been a rapid proliferation of city bars and nightclubs in recent years and people are fast shedding its inhibitions about alcohol as a lifestyle choice. This scenario has led to fears of an undocumented rise in alcohol abuse among all sections of society. Policies by the government has been laid down to regulate sales and pricing of alcohol, but not well improvised. Our aim was to find out the prevalence of alcoholism among adult males in a rural population and also to analyze its association between various factors. MATERIALS AND METHODS: A cross sectional study in a rural population at Kuthampakkam village, in Poonamallee block of Tiruvallur district in Tamil Nadu, India. The study population included adult male population. Simple random sampling method was adopted. A structured questionnaire was used to collect information regarding the background characteristics, history of alcoholism and certain social factors. STATISTICAL ANALYSIS: Data entry and analysis was done using Statistical Package for Social Sciences (SPSS) version 15 software. Descriptive statistics were calculated for background variables and the prevalence of the alcoholism. Chi-square test and p value were calculated to see the association between alcoholism and social factors. RESULTS: A total of 157 adult male were enrolled in the study. The mean age of the study participants was 37.20 years. The prevalence of alcoholism among the study participants was 35.7%. Among them only 4.5% who presented with symptoms of chronic alcoholism had taken treatment. Reasons for not taking treatment for alcoholism among study population were mainly due to their family problems (55.2%). CONCLUSION: Although alcohol consumption has existed for many centuries, the quantity, usage pattern, and resultant problems have undergone substantial changes over the past 20 years. These developments have raised concerns about the public health and social consequences. Awareness among the population and necessary rehabilitation and self-help programs will help in bringing down the prevalence of alcoholism. PMID- 25121006 TI - Stressing 'mental stress' in hypertension: a rural background study. AB - BACKGROUND: Modern life is full of hassles, deadlines, frustrations and demands. Mental stress or psychosocial stress is one of the major risk factor for hypertension which itself is the risk factor for various other cardiovascular diseases. OBJECTIVES: To find out the prevalence of hypertension among rural study population above 40 years of age and analyze the relationship between mental stress and Hypertension amongst them. METHODOLOGY: A cross-sectional descriptive study was undertaken in rural Maharashtra from January 2007 till December 2008. Systematic random sampling was done to cover 3600 sample size above 40 years of age. A protocol was devised containing requisite items of socio demographic data and data was collected from individual households with the help of ancillary staff. Mental stress score based on Presumptive stressful life event score (PSLES) was used. For statistical analysis, Chi-square test, F-test and Z test were used. RESULTS: Prevalence of hypertension was found to be 5.92%. Males had maximum cases of hypertension [169 (7.27%)] compared to females [44 (3.44%)] which was statistically significant (chi2 = 21.63, p < 0.001). The rise in number of cases with increasing age was observed. Significant number of cases [127 (7.68%, p= 0.00006)] were found in study population belonging to 'More stress' group. Mean mental stress score of hypertensive study subjects was significantly higher (219) than normotensive study subjects (157). Males had significant higher stress score in both hypertensive and Normotensive group. CONCLUSION: Total 213 cases of hypertension were detected (5.92%). As the stress increases, risk of hypertension increases. Statistically significant association was found between mental stress and hypertension for males. But in females, no such association was found. Mental stress definitely acts as risk factor for hypertension. Invention, propagation and practical application of various stress relieving measures & exercises should be done. PMID- 25121007 TI - Same dog bite and different outcome in two cases - case report. AB - There is still no cure for rabies and survival from clinical rabies is extremely rare. It is a preventable disease if the post exposure prophylaxis is initiated in time and administered as per WHO guidelines including administration of rabies immunoglobulin. The role of passive rabies immunization products is to provide the immediate availability of neutralizing antibodies at the site of the exposure before it is physiologically possible for the patient to begin producing his or her own antibodies after vaccination. In this case report, the same dog has bitten to a boy and to an adult. Local wound treatment and use of human rabies immunoglobulin as well as gluteal region as a site of bite were the probable reasons for survival of the boy. On the other hand no local wound treatment, no use of rabies immunoglobulin and finger as a site of bite are the probable reasons for death of an adult due to rabies. PMID- 25121008 TI - Topical vs Combination Ciprofloxacin in the Management of Discharging Chronic Suppurative Otitis Media. AB - OBJECTIVES: To study the microbial flora and determine the efficacy of topical ciprofloxacin ear drops in comparison with combination of topical and oral ciprofloxacin as first line management in patients diagnosed with chronic suppurative otitis media. MATERIALS AND METHODS: Prospective randomized interventional clinical trial on 100 patients who presented with an acute episode of CSOM to our outpatient department. RESULTS: In our study, topical ciprofloxacin therapy was found to be an effective treatment for an acute on chronic otitis media as was the combination therapy though the overall recurrence rate was found to be more in the former group. CONCLUSION: In the absence of systemic infection or serious underlying disease, topical antibiotics alone constitute first line treatment for most patients with chronic suppurative otitis media, finding no evidence that systemic antibiotics alone or in combination with topical preparations improve treatment outcomes compared with topical antibiotics alone. PMID- 25121009 TI - Recurrent angiofibroma of ethmoid region - a rare variant. AB - The common variant of angiofibromas of head and neck region is juvenile nasopharyngeal angiofibroma (JNA). However extranasopharyngeal angiofibromas (ENAF) occurs very rarely at any age in either sex, and they differ from classical JNA in incidence, clinical and radiological presentation. They form the differential diagnosis for any mass nose or nasal polyp. We present a case of recurrent angiofibroma of ethmoid region presented with recurrent lesion with bilateral proptosis and bossing of forehead. MRI showed involvement of bilateral nasal cavities, ethmoids and frontal sinuses with erosions of ethmoid roof and posterior table of frontal sinuses. Entire mass was excised by craniofacial resection which was histopathologically confirmed as Angiofibroma. PMID- 25121010 TI - Atrophic rhinitis presenting with ethmoidal mucocele: a case report. AB - Atrophic rhinitis (AR) is a chronic debilitating nasal mucosal disease predominantly prevalent in tropical countries. In the present case a 70-year-old female presented with a swelling in the right medial canthal area for six months and had features of Atrophic rhinitis with large septal perforation leading to saddle nose deformity. Computed tomography pictures were suggestive of ethmoidal mucocele and was later decompressed endoscopically. The sequelae and complications of AR like nasal septal perforation, saddle nose deformity, chronic rhinosinusitis (CRS), local and systemic spread of infection, atrophic pharyngitis, laryngitis, dacryocystitis and nasal myiasis have been reported in literature. To the best of our knowledge, this is the first reported case of AR presenting with ethmoidal mucocele. A case of AR with CRS is to be treated with caution as it can lead to complications as it is often neglected. PMID- 25121011 TI - Evaluation of outcome of corrective ulnar osteotomy with bone grafting and annular ligament reconstruction in neglected monteggia fracture dislocation in children. AB - INTRODUCTION: Neglected Monteggia fracture dislocation in the paediatric age group constitutes significant disability in respect to pain, stiffness, deformity, neurological compromise and restriction of activities of daily living. MATERIALS AND METHODS: A longitudinal prospective study was done on 21 children with old Monteggia fracture-dislocation which included 18 cases of Bado type I and 3 cases of Bado type III at the department of orthopaedics, IPGME&R,SSKM hospital, Kolkata, India between 2007 and 2012. All were treated by modified Hirayama corrective osteotomy of ulna with wedge bone grafting along with restoration of its length and reconstruction of annular ligament using Bell Tawse method and fixation of radial head with transcapitellar Kirschner wire. Average follow up period was 5.5 years. RESULTS AND ANALYSIS: Results were evaluated on the basis of 100 point Mayo Elbow Performance Index, radiology and questionnaire. The mean postoperative increase in Mayo Elbow Performance Index score was 30 with average increase in the range of movement by 30o. In three cases, there was subluxation of radial head and in addition one had transient palsy of posterior interosseous nerve. Three cases showed distortion of the radial head which were insignificant functionally. Results of improvement in mean MEPI were analysed by chi-square test and was significant at 0 .01 level of significance. CONCLUSION: Study showed good results with modified Hirayama osteotomy with annular ligament reconstruction using Bell Tawse procedure which is a more biological option for restoration of elbow biomechanics. PMID- 25121012 TI - Vibration Therapy in Management of Delayed Onset Muscle Soreness (DOMS). AB - Both athletic and nonathletic population when subjected to any unaccustomed or unfamiliar exercise will experience pain 24-72 hours postexercise. This exercise especially eccentric in nature caused primarily by muscle damage is known as delayed-onset muscle soreness (DOMS). This damage is characterized by muscular pain, decreased muscle force production, reduce range of motion and discomfort experienced. DOMS is due to microscopic muscle fiber tears. The presence of DOMS increases risk of injury. A reduced range of motion may lead to the incapability to efficiently absorb the shock that affect physical activity. Alterations to mechanical motion may increase strain placed on soft tissue structures. Reduced force output may signal compensatory recruitment of muscles, thus leading to unaccustomed stress on musculature. Differences in strength ratios may also cause excessive strain on unaccustomed musculature. A range of interventions aimed at decreasing symptoms of DOMS have been proposed. Although voluminous research has been done in this regard, there is little consensus among the practitioners regarding the most effective way of treating DOMS. Mechanical oscillatory motion provided by vibration therapy. Vibration could represent an effective exercise intervention for enhancing neuromuscular performance in athletes. Vibration has shown effectiveness in flexibility and explosive power. Vibration can apply either local area or whole body vibration. Vibration therapy improves muscular strength, power development, kinesthetic awareness, decreased muscle sore, increased range of motion, and increased blood flow under the skin. VT was effective for reduction of DOMS and regaining full ROM. Application of whole body vibration therapy in postexercise demonstrates less pressure pain threshold, muscle soreness along with less reduction maximal isometric and isokinetic voluntary strength and lower creatine kinase levels in the blood. PMID- 25121013 TI - A Study of Etiological Pattern in an Epidemic of Acute Febrile Illness during Monsoon in a Tertiary Health Care Institute of Uttarakhand, India. AB - BACKGROUND: Many parts of India are endemic for the dengue, malaria, typhoid and scrub typhus infections. The relative contribution of these illnesses in an outbreak of acute febrile illness is not known in this region. OBJECTIVE: The present study was conducted to find out the etiological pattern in an epidemic of acute febrile illness in Uttarakhand during the monsoon period. The study also focuses on concurrent infections and tries to find out the mortality outcomes. MATERIALS AND METHODS: A retrospective study of four months was conducted on 1141 patients who presented with fever, and were suspected to have dengue, malaria, typhoid or scrub typhus. Patients of 12-years of age or above were included in the study. Serological tests for dengue, malaria, typhoid and scrub typhus were performed. Slides for malaria parasite were examined. In case of enteric fever only culture positive cases were included in the study. RESULT: Among the 1141 febrile patients dengue was detected in 812(71.2 %), malaria in 146(12.8%), typhoid in 92(8.1%) and scrub typhus in 69(6.0%) cases. Mixed infection was noted in 22(1.9%). CONCLUSION: Maximum (71.2 %) cases of fever were caused by dengue but significant number (32.3%) of patients suffered from malaria typhoid and scrub typhus. Many (1.9%) suffered from concurrent and multiple infections. PMID- 25121014 TI - Microbiological Profile and Drug Sensitivity Pattern among Community Acquired Pneumonia Patients in Tertiary Care Centre in Mangalore, Coastal Karnataka, India. AB - BACKGROUND: Community Acquired Pneumonia (CAP) is the most common respiratory tract infection in day to day practice. The knowledge of organism commonly causative of CAP helps in early empirical treatment initiation. AIM: To study the microbiological profile of patients with community acquired pneumonia and to study drug sensitivity pattern. METHODS: Hospital based cross sectional study among 100 patients with CAP was conducted in a tertiary care hospital of Southern India. Sputum culture showed that out of 100 patients 39 had an identifiable etiology with 12 patients having evidence of mixed infection. RESULT: Micro organisms isolated in sputum culture were Streptococcus pneumoniae (31%) followed by, Pseudomonas pyogens (15%), Klebsiella pneumoniae (13%). AFB smear was found to be positive in 6 patients. Organisms were found to be sensitive for piperacillin plus tazobactum (41%), aminoglycocides (amikacin-46%, gentamicin 31%), third generation cephalosporins (Cefotaxim-36%, Ceftriaxone-18%) and macrolides (Erythromicin-31%, Azithromycin-18%). Sensitivity to chloramphenicol was observed in 31% sputum culture positive patients. Ciprofloxacin sensitivity was seen among 49%. CONCLUSION: Most of the organisms were found to be sensitive to monotherapy with extended spectrum beta lactamases, third generation cephalosporins, fluroquinolones, macrolides. PMID- 25121015 TI - Ischaemic Stroke Following Percutaneous Transluminal Coronary Angioplasty (PTCA): A Rare Complication. AB - Stroke following coronary interventions is a devastating and most dreaded complication with significant morbidity and mortality. Various factors have been ascribed for this complication including the technical errors. We hereby describe such a patient who presented to us with the diagnosis of acute coronary syndrome and underwent percutaneous coronary intervention (PCI) but unfortunately developed left sided hemiparesis due to ischaemic stroke (right middle cerebral artery). She was managed as per the standard treatment protocols for acute coronary syndrome and later on for ischaemic stroke which she nicely responded to and was discharged in a haemodynamically stable condition. On follow-up after 15 days, she was totally symptom-free. We will discuss all the possible preventive and treatment measures for this rare complication of (PCI). PMID- 25121016 TI - Bi-opercular Syndrome: A Case Report and Minireview. AB - Opercular syndrome is a well known but neglected entity and is quite common, but it is difficult for non-neurologists to diagnose this entity because of lack of awareness. Inability to speak and swallow with dissociation of automatic voluntary movements in the affected muscles are the essential features of this syndrome. The aetiology in most of the reported cases is vascular (thrombosis or embolism) involving branches of middle cerebral artery supplying the opercular area. We are reporting a case of "bilateral opercular syndrome" caused by stroke in a young patient. He had sudden onset of bilateral facial and tongue palsy, inability to speak and swallow, but with preserved automatic functions. He was mute but verbal comprehension was normal. CT head revealed bilateral perisylvian infarcts. PMID- 25121017 TI - Churg strauss syndrome - a case report. AB - A male aged 45-years presented with complaints of fever for 7days, cough, breathlessness for 4 days, tingling of hands, feet and weakness of both hands and feet for 4 days duration. He was a known asthmatic with history of recurrent sinusitis in the past. On examination he had bilateral polyphonic wheeze and evidence of distal asymmetric sensory neuropathy with motor weakness. And on investigation he had eosinophilia, pulmonary function test showed reversible airway obstruction,nerve conduction studies revealed mononeuritis multiplex, muscle biopsy suggestive of eosinophilia infiltration, nerve biopsy suggestive of vacuities, 2DECHO showed RWMA in inter ventricular septum, Coronary angiogram showed narrowing in distal LAD territory. In view of sinusitis, asthma, eosinophilia, tissue infiltration by eosinophils we made a diagnosis of Churg Strauss syndrome. PMID- 25121018 TI - Multiple abdominal veins thrombosis secondary to protein s deficiency - a case report. AB - Abdominal venous thrombosis may present either as Budd-Chiari syndrome (BCS) caused by hepatic vein or proximal inferior vena cava (IVC) obstruction or as an extra hepatic portal obstruction (EHPVO) caused by Portal vein thrombosis or mesenteric vein thrombosis, but a mixed involvement is uncommon. Multiple abdominal venous obstructions presenting with thrombosis of hepatic vein, IVC, portal vein and renal vein are very rarely seen . We are reporting a rare case with thrombosis of IVC, hepatic vein, portal vein and renal vein, with protein S and protein C deficiencies, which was managed by giving anticoagulant therapy. PMID- 25121019 TI - High blood pressure in dialysis patients: cause, pathophysiology, influence on morbidity, mortality and management. AB - Dialysis is initiated in a patient with End stage renal disease. The recent guidelines suggest the initiation of dialysis when symptoms and signs of kidney failure are present and not merely a decrease in GFR. The most common complication postdialysis is the occurrence of hypotension. However many dialysis patients are found to be hypertensive. In this article, we mention the cause and pathophysiology of hypertension in dialysis patients and its management. PMID- 25121020 TI - Burden of antibiotic resistance in common infectious diseases: role of antibiotic combination therapy. AB - Globally, antimicrobial resistance is alarming concern especially in commonly reported disease entities like respiratory tract infection, enteric fever and infections associated with gram-negative bacilli (GNB). Rational use of antimicrobial drugs reported significant decrease in bacterial burden and may also reduce the risk of disease progression. However, at times in particular indication, certain patient and pathogen factor limits the selection and use of specific antibiotic therapy while in some case, due to presence of additional risk factor, aggressive therapy is required to achieve clinical reemission and prevent complications. Delay in start of suitable antibiotic therapy is another imperative factor for treatment failure and rise of drug resistance. With rapidly increasing antibiotic resistance and decline in new antibiotic drug development, the toughest challenge remains to maintain and preserve the efficacy of currently available antibiotics. Therefore, the best rational approach to fight these infections is to 'hit early and hit hard' and kills drug-susceptible bacteria before they become resistant. The preferred approach is to deploy two antibiotics that produce a stronger effect in combination than if either drug were used alone. Various society guidelines in particular indications also justify and recommend the use of combination of antimicrobial therapy. Combination therapies have distinct advantage over monotherapy in terms of broad coverage, synergistic effect and prevention of emergence of drug resistance. PMID- 25121021 TI - Penile incarceration with encircling metallic objects: a study of successful removal. AB - OBJECTIVE: This article aimed to study the various treatment options according to the grading scale for penile incarceration. MATERIALS AND METHODS: A retrospective review, of all the case files of patients presented with penile incarceration with encircling metallic object was performed. The patients were analyzed for age, marital status, motive, object used, who applied it, trauma grade, duration of incarceration, removal technique, removal time, anesthesia used and recovery time. RESULT: A total of seven patients were identified. The average age was 46.71 years. Self-sexual gratification was the most common motive (five patients). Six patients presented within 24 hours. Grade II of injury was commonest type of injury seen in five patients.The technique of removal chosen was according to grade of penile injury, duration of incarceration and type of object used. Spinal anesthesia was used in most of the cases (five patients). CONCLUSION: Penile incarceration with encircling metallic objects is a rare presentation and requires urgent intervention according to trauma grade to prevent complications. PMID- 25121022 TI - To study the levels of C - reactive protein and total leucocyte count in patients operated of open and laparoscopic cholecystectomy. AB - BACKGROUND: The recovery from laparoscopic cholecystectomy (LC) is rapid and most of the patients are discharged on the 1st post-operative day. There is an increased concentration of certain serum proteins, known as acute-phase reactive proteins (APRP) during the post-operative period depends on the degree of tissue damage and the inflammatory reaction. There is a direct positive correlation between the concentrations of APRP, especially C-reactive protein (CRP), and the severity of inflammation. This study was done to study the levels of C - reactive protein and Total Leucocyte Count in patients operated either by Open Cholecystectomy (OC) and Laparoscopic Cholecystectomy (LC). MATERIALS AND METHODS: This prospective study was conducted on 50 patients after approval from the Institutional Ethics Committee. Twenty five patients underwent open cholecystectomy and the other 25 had laparoscopic cholecystectomy. The pre and post operative concentrations of serum C-reactive protein (CRP) and total leukocyte count (TLC) were compared in both the groups. RESULTS: There were no differences in the preoperative serum CRP and TLC concentrations - in both the groups. Serum CRP rose significantly following OC compared to that of patients who underwent LC (10.52 +/- 1.96 mg% vs. 8.88 +/- 1.23 mg %). There were also significant differences in the post-operative TLC ( 9.49 +/- 1.05 m/mm3 for the OC group vs. 8.57 +/- 1.31 m/mm3 for the LC group), and the post-operative hospital stay (5.5 +/-1.5 days vs. 1.9 +/- 0.9 days). There was no correlation between serum CRP concentrations and the other post-operative parameters. CONCLUSION: The study provided the biochemical evidence supporting the clinical observation that LC is far less traumatic to the patient than OC. PMID- 25121023 TI - Clinical examination allied to ultrasonography in the assessment of new onset gynaecomastia: an observational study. AB - AIM: New onset gynaecomastia is a relatively common presentation to breast surgical services. The main aim of clinical and radiological evaluation is to exclude the presence of concurrent breast cancer. There exists much variability in the clinical assessment of male patients presenting with new onset gynaecomastia. MATERIALS AND METHODS: In the presented pilot study, all the male patients presenting with new onset gynaecomastia to our department over a period of two years were studied. RESULTS: Fifty three patients presented with new onset gynaecomastia during the study period. Clinical examination allied with ultrasonography confirmed benign breast disease in 50 patients with only three patient requiring breast biopsy to exclude malignancy. We detail the efficacy of utilising clinical examination in conjunction with ultrasonography to evaluate new onset gynaecomastia. CONCLUSIONS: We show that clinical examination used in conjunction with ultrasonography is both highly sensitive and specific for detecting male breast cancer in patients presenting with new onset gynaecomastia. PMID- 25121024 TI - Isolated duodenal adenoma presenting as gastrointestinal bleed - a case report. AB - Duodenal polyps are rare lesions in patients undergoing Esophago-gastro duodenoscopy (EGD), and the prevalence varies widely with range of 0.3-4.6% of cases. Duodenal adenomas most commonly occur in association with familial adenomatous polyposis. Isolated occurrence of such adenomas is very rare and presentation as upper gastrointestinal (GI) haemorrhage is even rarer. We herein report a case of elderly male patient presenting to emergency department with features of upper GI bleeding. Patient was resuscitated followed by EGD was done. On EGD bleeding duodenal polyp was found and endoscopic polypectomy was done to control the bleeding. Subsequent colonoscopy was done and was normal. The histopathological examination of the polypectomy specimen revealed tubular adenomatous polyp which is a premalignant condition. We also highlight the clinical presentation, histological types and treatment modalities available in the literature. However, there is lack of consensus regarding the outcome of various procedure described in the literature. PMID- 25121026 TI - Extraocular sebaceous carcinoma on the chest wall - a case report. AB - Sebaceous carcinoma is a rare aggressive skin cancer derived from the epithelium of sebaceous glands. Sebaceous carcinomas are generally divided as ocular or extraocular locations. Very few cases of extra ocular sebaceous carcinomas have been reported till date. Among them only six cases were reported which were on the chest wall. We are hereby reporting the seventh case of sebaceous carcinoma on the chest wall. The disease exhibits diverse clinical presentations and histologic patterns, often resulting in a delay in an accurate diagnosis as it may mimic many other cutaneous malignancies like Dermatofibrosarcoma protuberance Basal Cell Carcinoma or Squamous Cell Carcinoma. High degree of suspicion is required and sebaceous carcinoma should be considered as one of the differential diagnosis for an ulceroproliferative growth on the skin. PMID- 25121025 TI - Isolated splenic hydatidosis. AB - A 27-year-old female presented with pain in the left hypochondrium for the past six months. An abdominal examination revealed mild splenomegaly. An abdominal ultrasonography showed two cystic lesions at the superior pole of the spleen. Contrast enhanced CT scan abdomen confirmed the USG findings, demonstrating splenomegaly with nonenhancing cystic lesions having internal septations and suspicious daughter cysts within it, strongly suggestive of hydatid cysts. On serological testing, the patient was positive for IgG Antibodies against Eccinococcus. Following Pneumococcal vaccination, splenectomy was performed taking precautions to prevent accidental rupture or spillage of contents into the peritoneum. The postoperative period was uneventful with the patient making a swift recovery. Histopathological examination revealed extensive necrosis within the cysts. In the midst of the necrotic material, hooklets were seen. These features were consistent with a diagnosis of an infected Hydatid cyst. It is of utmost importance that a correct preop diagnosis is made since all precautions must be taken to prevent dissemination or seeding of the surgical field. Death has been reported due to anaphylactic shock resulting from spillage during excision or biopsy. The most important factor in diagnosing splenic hydatid cyst is the awareness of its possibility. PMID- 25121027 TI - Spontaneous Caecal Perforation Associated with Ogilvie's Syndrome Following Vaginal Delivery - A Case Report. AB - Acute pseudo-obstruction of the large bowel, Ogilvie's syndrome, can occur in the postpartum period following caesarean section which can result in caecal dilatation and may progress to perforation. This is quiet rare following normal vaginal delivery. Only two previous reports have been found in the English literature. We report a case of Ogilvie's syndrome with caecal perforation following normal vaginal delivery. PMID- 25121028 TI - Myofibroblastoma of female breast masquerading as schirrous malignancy - a rare case report with review of literature. AB - Myofibroblastoma is a rare benign mesenchymal tumour of the breast commonly reported in males. It is a spindle cell neoplasm exhibiting myofibroblastic differentiation with characteristic immunohistochemical staining. Herein, we present a case of myofibroblastoma in a premenopausal female which was mimicking like malignancy clinically. Lump was growing rapidly in size measuring 8 cm x 6 cm and stony hard in consistency. Mammogram showed a large homogeneous hyperdense lump suggestive of fibroadenoma, Hamartoma and fibromatosis. FNAC and trucut biopsy of mass could not be done due to stony hard consistency. Hence excision biopsy was done. Histopathological examination revealed the tumour as myofibroblastoma. Immunohistochemical staining for markers of myofibroblasts like CD-34 and Vimentin showed strong positivity. A negative expression for cytokeratin was noted. This case is presented for its rarity, unusual clinical presentation and stony hard consistency. PMID- 25121029 TI - Omental torsion. AB - Torsion of greater omentum is one of the rare causes of acute abdominal pain. It can be primary or secondary. Primary Omental Torsion (POT) occurs because a mobile, thicken segment of omentum rotates around a proximal fixed point in the absence of any associated or secondary intra-abdominal pathology. Secondary omental torsion is associated with a number of pre-existing conditions most common among them is inguinal hernia, other causes include tumours, cysts, internal or external herniation, foci of intra-abdominal inflammation and postsurgical wound or scarring. Torsion of omentum causes twisting of omentum along its long axis resulting in impaired blood supply. This rare condition is more predominant in middle-aged males. It clinically mimics acute appendicitis. It should be kept in mind as a differential diagnosis for acute abdomen. Laparoscopy can aid in diagnosis and management but explorative laparotomy is the definitive and therapeutic procedure of choice. However the condition is not life threatening as omentectomy reduces the inflammation and focus of adhesions within the abdomen. PMID- 25121030 TI - HBV & HCV - awareness in acute abdomen emergency cases. AB - A study was conducted on 100 cases of Acute abdomen admitted in surgery department of Govt Medical college and Rajendra Hospital, Patiala, India. Study group included patients with different abdominal emergencies, e.g. gastrointestinal perforation, intestinal obstruction, acute appendicitis, acute cholecystitis, pancreatitis etc. Out of these, three cases were positive for HBsAg alone, one for anti Hepatitis C-Virus (HCV) alone and one was positive for both HBsAg and anti HCV. PMID- 25121032 TI - Clinico-pathological profile of adnexal torsion cases: a retrospective analysis from a tertiary care teaching hospital. AB - INTRODUCTION: Torsion of the adnexa is a rare condition which can be potentially lethal for the women. The clinical presentation can be varied and can be seen in any age group. Understanding the clinical and pathological profile of patients suffering from adenexal torsion can guide the clinicians in diagnosing and managing the condition. OBJECTIVE: To analyze the clinical and pathological profile of adnexal torsion cases in a tertiary care teaching hospital. MATERIALS AND METHODS: The study was a retrospective analysis of hospital records. It included all cases of adnexal torsion that underwent laprotomy between January 2007 to December 2012 in a tertiary care teaching hospital. The study was approved by the Institute's human Ethics Committee. RESULTS: A total of 18 patients were included in the study. Majority (66.7%) of participants were in the reproductive age group. Abdominal pain was the most common symptom seen in 77.8% of patients. The other symptoms were abdominal distension, back ache and dysuria. Majority of the women belonged to Para 2 (44.4%) and Para 3 (27.8%). The proportion of women with one and two LSCS was 11.1% and 16.7% respectively. Tenderness (38.9%), mass (22.2%) were the common per abdomen findings. Perspeculum findings were normal in majority (88.9%) of the participants. About 39.2% of the patients presented with a mass in either fornices or pouch of Douglas on pervaginal examination. The side of lesion was only on right in 9 (50%) , only left in 7(38.9%) and both sides in 2 (11.1%) of cases. On histopathological examination, of the lesions there were mucinous cystadenoma (33.3%) serous cystadenoma (16.7%) and benign cystic teratoma (16.7%) as most common lesions. CONCLUSION: Adnexal torsion, though a rare clinical condition can present as an emergency most of the times. High index of suspicion is required for diagnosis, as the clinical presentation can be varied. But the diagnosis can be made certain only on the operating table, either by laparoscopy. Avoiding a delay in operating upon the patient will help prevent complications, and aid in conserving the ovary. PMID- 25121033 TI - Pregnancy with gilbert syndrome - a case report. AB - A primigravida presented to us at 32 weeks of gestation with vomiting, myalgia and jaundice. On examination she had icterus, she was dehydrated, uterus was corresponding to dates and the fetal heart rate was good. On evaluation, all the investigations were normal except mild unconjugated hyperbilirubinaemia and hypoglycaemia. Based on the above findings we derived at a diagnosis of Gilbert syndrome. Dehydration due to vomiting aggravated her jaundice. On correcting her dehydration jaundice resolved, patient improved symptomatically and was discharged two days later. She was later admitted at term and underwent emergency caesarian section in view of fetal distress. Mother and baby were fine postoperatively and was discharged on the fifth postoperative day Gilbert syndrome is rare in obstetric practice. Virtually all patients have decreased activity of Uridine diphosphate glucuronosyl transferase (UDPGT). The case is reported due to its rarity. PMID- 25121031 TI - Knowledge, Awareness and Prevention of Cervical Cancer among Women Attending a Tertiary Care Hospital in Puducherry, India. AB - BACKGROUND: Cervical cancer is one of the most common cancers among women worldwide, with highest mortality in India. The incidence and mortality of cervical cancer can be reduced by screening women for precancerous lesion and by administration of human papilloma virus vaccine to adolescent girls. Knowledge of the women about cervical cancer and awareness about its prevention are the key factors that determine their utilization of screening services. METHODS: A cross sectional survey of women attending Gynaecology Out-Patient Department (OPD) in a tertiary care hospital in Puducherry was conducted. Information about their knowledge of cervical cancer, awareness of its prevention and their socio demographic characters were collected. RESULTS: Mean age of the study population was 40.45 +/- 12 years. Less than half of the study population (178, 44.5%) knew about cervical cancer. Less than one-fourth of the population knew about screening services for prevention of cervical cancer, and majority (389, 97.2%) were not aware of vaccination as prevention for cervical cancer. CONCLUSION: Our study population shows poor knowledge about cervical cancer and is unaware of the concept of prevention. Hence extensive health education to the public is needed regarding cervical cancer and its prevention. PMID- 25121034 TI - Hypokalemic paraplegia in pregnancy. AB - Hypokalemic myopathy may range from numbness/weakness to complete paralysis. The aetiology may be congenital or acquired. It is characterized by acute muscular weakness with low levels of potassium (<3.5 meq/L). We present a case of 26-year old multigravida at 36 weeks of gestation with gestational hypertension on treatment, who came with acute onset of pain, numbness and weakness of both legs which worsened following betamethasone injection. She was diagnosed to have Hypokalemic paralysis with potassium levels of 2.1 meq/L. The medical profile remitted promptly on intravenous potassium replacement. Pregnancy was continued till 37 weeks with oral potassium supplements, antihypertensives and regular monitoring of serum potassium levels. The pregnancy was terminated after 37 weeks in view of gestational hypertension. Postpartum period was uneventful, patient was discharged after two weeks when potassium levels and BP returned to normal. PMID- 25121035 TI - A Rare Case of Delayed Pulmonary Oedema due to Methemoglobinemia Following Laparoscopic Chromopertubation with Methyleneblue. AB - The patient is a young infertile lady with right tubal block on hysterosalpingogram was subjected for diagnostic hysterolaparoscopy.Hysterolaparoscopy findings were normal. Transcervical chromopertubation was performed using 20 -30 ml of diluted methylene blue through hysterosalpingogram cannula. Hesitant flow of dye was noted on left side after 2 3 flushing attempts. Ampullary block noted on right side with no spillage of the dye. Patient made an uneventful anaesthetic recovery. Five hours later patient developed tachypnea,hypotension and bluish colored urine was drained. She was shifted to ICU and patient eventually recovered after hemodynamic support with oxygen, steroids and inotropes. Spectrophotometric analysis showed methemoglobin levels of 26.3%. This case is reported for its rare but potentially fatal complication of pulmonary oedema following methylene blue. In this case pulmonary oedema manifested late in the postoperative period compared to other reported cases in the literature where pulmonary oedema was seen during intraoperative period. PMID- 25121036 TI - Modified pelvic floor repair in prolapsed uterus, with total prevention of vault prolapse. AB - In and around Ammapettai, a rural area with an economically backward community, 515 cases were operated for prolapsed uteri, by doing modified pelvic floor repairs (Dr. Sunthanthradevi's method), without any incidence of vault prolapse, with patients being followed up for two years after their surgeries. PMID- 25121037 TI - A rare case of accidental esophageal perforation in an extremely low birth weight neonate. AB - Spontaneous perforation of esophagus in neonates is a rare occurrence. However iatrogenic perforation of the esophagus is not that uncommon, and is most frequently seen in preterm and low birth weight infants. In premature infants, an esophageal perforation (EP) mainly occurs while inserting an orogastric tube. The commonly reported symptoms of EP are sudden onset respiratory distress, due to the pleural effusion and pneumothorax. In our case neonate presented with apnea requiring ventilation. We present a rare case of an Extremely Low Birth Weight (ELBW) neonate with an iatrogenic esophageal perforation who presented with recurrent apneas, outlining aspects of diagnosis and management. PMID- 25121038 TI - A case of periodic hypokalemic paralysis in a patient with celiac disease. AB - A 4-year-old male child presented with recurrent episodes of diarrhoea for 6 months, each episode associated with weakness of all four limbs and documented hypokalemia who on examination had some pallor, short stature, flaccid quadriparesis with absent DTR. The patient responded clinically and biochemically to potassium supplement. TTG and Intestinal biopsy confirmed celiac disease. Patient was put on gluten free diet and patient is doing well with no recurrence. We present a case of Recurrent hypokalemic paralysis with previously unsuspected celiac disease who was not in celiac crisis. PMID- 25121039 TI - Papillary carcinoma in median aberrant thyroid (ectopic) - case report. AB - Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed. PMID- 25121040 TI - Magnetic resonance imaging (MRI) evaluation of perianal fistulae with surgical correlation. AB - AIMS: The purpose of the study was to evaluate the role of Magnetic Resonance Imaging in detection and characterization of perianal fistulae and correlating it with surgical findings. METHODS: Fifty consecutive patients with suspected perianal fistulae having one or more external openings were prospectively selected for MRI evaluation. Previously operated or patients with recurrent perianal disease were excluded from the study. MRI findings were recorded according to "St. James's University Hospital MR Imaging Classification of Perianal Fistulae" and correlated with surgical observations. Finally, comparison between T2-weighted fat saturated and postcontrast T1-weighted fat saturated sequences was done. RESULTS: Amongst the total of 50 patients, per-operative findings confirmed perianal fistulae in 45 patients. The sensitivity and specificity of MRI in correctly detecting and grading the primary tract was found to be 95.56% and 80% respectively; for abscess, it was 87.50% and 95.24% respectively. High sensitivity was also discerned in identification of secondary tract (93.75%), correct localization of internal opening (95.83%) and for correctly detecting the horse-shoeing (87.50%). Our assumption of null hypothesis was accepted on comparing results of T2-weighted fat saturated sequences and postcontrast T1-weighted fat saturated sequences. CONCLUSION: Magnetic Resonance Imaging (MRI) was highly accurate in assessment of surgically important parameters (primary tract and its grading, internal opening, secondary tract, abscess, horseshoeing) of perianal fistulae. Comparison of results of imaging findings on T2-weighted and postcontrast T1-weighted fat saturated sequences were statistically similar, so contrast study can be omitted, particularly while evaluating primary / previously unoperated perianal fistulae. PMID- 25121042 TI - Comparison of 128-Slice Dual Source CT Coronary Angiography with Invasive Coronary Angiography. AB - BACKGROUND: Coronary artery disease (CAD) is one of the leading cause of the morbidity and mortality in India as well as worldwide and last decade has seen a steep rise in incidence of CAD in India. Direct visualization of the coronary arteries by invasive catheterization still represents the cornerstone of the evaluation of CAD. Cardiac imaging is a challenge of 21 (st) century and is being answered by 128 slice dual source CT as it has good temporal resolution, high scanning speed as well as low radiation dose. AIM: To assess the diagnostic accuracy of 128-slice dual source CT Cardiac Angiography in comparison with Conventional Catheter Cardiac Angiography. MATERIALS AND METHODS: Forty patients attending the cardiology OPD with complaint of chest pain and suspected of having CAD were evaluated by CT coronary angiography and conventional invasive Catheter coronary angiography and the results were compared. All patients were checked for serum creatinine and ECG before the angiography. Computed Tomography (CT) coronary angiography was done using SIEMENS 128-slice Dual Source Flash Definition CT Scanner under either Retrospective or Prospective mode depending on the heart rate of the patient. Oral/IV beta-blocker were used whenever required. RESULTS: Coronary arteries were assessed as per 17- segment AHA model. A total of 600/ 609 segments were evaluable in 40 suspected patients on CT coronary angiography, of which 21 were false positives and 8 were false negatives with specificity of 95.12% and sensitivity and positive predictive value of 95.26% & 88.46% respectively. CONCLUSION: Non-invasive assessment of CAD is now possible with high accuracy on 128-slice dual source CT scanner. PMID- 25121041 TI - Allergic Bronchopulmonary Aspergillosis (ABPA)-The High Resolution Computed Tomography (HRCT) Chest Imaging Scenario. AB - INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) is a progressive disease which can lead to recurrent exacerbations, bronchiectatic changes and end stage fibrosis. Early diagnosis and treatment prevents its progression and alleviate its clinical manifestations. High resolution CT of the chest has emerged as a promising investigation for its diagnosis. AIMS AND OBJECTIVES: To review the high resolution computed tomography (HRCT) chest manifestations in ABPA patients. MATERIALS AND METHODS: This study included 110 patients with ABPA who had undergone HRCT of the chest in the routine diagnostic workup for ABPA. The scans were assessed for changes in bronchi, parenchyma and pleura and findings consistent with ABPA were evaluated. RESULTS: HRCT chest was normal in 24 patients. 86 patients demonstrated central bronchiectasis with predilection for upper and middle lobes. Centrilobular nodules with or without linear opacities (tree in bud pattern), mucoceles and high-attenuation mucus were seen in 86%, 59% and 36% patients respectively. CONCLUSION: Central bonchiectasis combined with centrilobular nodules and mucus impaction (especially high attenuation mucus) strongly favour the diagnosis of ABPA. PMID- 25121043 TI - High Resolution Computed Tomography Lung Spectrum in Symptomatic Adult HIV Positive Patients in South-East Asian Nation. AB - BACKGROUND: Pulmonary infections remain a leading cause of morbidity and mortality and one of the most frequent causes of hospital admission in HIV infected people worldwide. HRCT may be useful in the evaluation of patients with suspected pulmonary disease. The aim of given study was to determine the High Resolution Computed Tomography spectrum of lung parenchymal and interstitial imaging findings in HIV infected patients presented with chest symptoms. MATERIALS AND METHODS: This study was conducted in a tertiary health care centre, New Delhi, India. The study consisted of 45 patients. A thorough clinical history of all the HIV positive patients presenting with suspicion of pulmonary disease was taken. General physical and respiratory system examination of all patients was done. HRCT scans of the chest were done in all the cases taken in the study. RESULTS: Maximum number of patients was in age group 31-40 years (24 cases). Out of 45 patients included in our study, 32 (71%) were male and 13 (29%) were female. In our series of 45 patients, 62.2% of patients were diagnosed as having pulmonary tuberculosis, followed by bacterial infection in 20% cases and Pneumocystis jiroveci pneumonia (PJP) in 8.9% patients, while 8.9% of the study did not reveal any significant abnormality. Maximum number (22/28) of patients with pulmonary tuberculosis were indentified to have nodular opacities. The most common HRCT finding in bacterial infection was lobar consolidation. The most common HRCT finding in patients with PCP was diffuse ground glass opacities in mosaic pattern of distribution. CONCLUSION: HRCT is a highly sensitive tool for detecting lung parenchymal and interstitial lesions and allows better characterization of the lesions. HRCT findings should always be correlated with clinical findings, CD4 counts and other available investigations before arriving at a diagnosis or differential diagnosis. PMID- 25121044 TI - Unilateral right pulmonary agenesis in adulthood. AB - Congenital malformations of the lung, which may vary in degrees of severity, are very rare diseases. Pulmonary artery agenesis is a rare anomaly that may occur during the early involution of the proximal portions of the sixth aortic arch, during embryological development of the heart. This agenesis may be accompained by a complete or partial absence of the lung and its bronchus on the same side, which is diagnosed as pulmonary agenesis. In the great majority of the cases, the diagnosis is usually made at or soon after birth and it can be associated with multiple anomalies. However, extremely rare asymptomatic cases may go unnoticed until adulthood. We are presenting a patient with unilateral right pulmonary agenesis, who survived through adulthood without any symptoms and other congenital anomalies. The multislice computed tomography findings and differential diagnoses have been discussed. PMID- 25121045 TI - Role of CT Imaging with Volume Reconstruction in Hemi Facial Hypertrophy: A Pediatric Case Report. AB - Hemifacial hypertrophy is a rare congenital disorder more common in males.It involves the soft tissue, hard bones and teeth of the face.Its etiology is unknown and multiple theories have been postulated. We present a 6-year-old male with hemifacial hypertrophy and describes the importance of CT volume reconstruction in this condition. PMID- 25121046 TI - Genetic polymorphism of interleukin-18 gene promoter region in rheumatoid arthritis patients from southern India. AB - BACKGROUND: Interleukin-18 (IL-18) is a pro inflammatory cytokine which plays a key role in the acute and chronic inflammatory phases of Rheumatoid Arthritis (RA). The Single Nucleotide Polymorphisms (SNPs) of IL-18 gene promoter region at positions -137 and -607, are postulated to be associated with RA. To test this, this study aimed to identify the association between these SNPs of the IL-18 gene promoter region of RA in south Indian patients. MATERIALS AND METHODS: This study was carried on 190 subjects among which 90 were RA patients and 100 were age and sex matched controls. Genomic DNA was extracted by Salting out method. IL 18 gene promotor region SNPs, IL 18 - 607 and IL 18 -137 were amplified by using sequence specific primers. The amplified products of different samples were separated by using a 1.5% agarose gel, stained with ethidium bromide and photographed. All statistical analyses were carried out by using SYSTAT 12 software. RESULTS: At position 607, the frequencies of C allele, CC genotype, A allele and AA genotype were found to be significantly higher in patients and controls respectively and there was no significant difference in CA genotype. At position 137, there was no significant difference between the two groups with regard to G and C allelles but there was a significant increase in GG genotype of patients and CC genotype of controls. There was no association between duration of morning stiffness, rheumatoid factor positivity or negativity, age of onset and gender with distribution of genotypes and alleles. CONCLUSION: C allele, CC genotype at position-607 and GG genotype at position-137 are risk factors and A allele, AA genotype at position-607 and CC genotype at position-137 have protective effect for RA. PMID- 25121047 TI - A Retrospective Clinical Study of the Etiology and Post-operative Visual Outcome of Rhegmatogenous Retinal Detachment. AB - AIM: To study the etiology of rhegmatogenous retinal detachment and visual outcome after retinal detachment surgery. MATERIALS AND METHODS: Retrospective study conducted at the tertiary eye care hospital over a period of one year. Thirty eyes of 30 patients were included after fulfilling the inclusion criteria. Complete ocular examination details of each patient such as visual acuity for distant vision (checked with Snellen's acuity chart),slit lamp examination, fundus examination (done with +90D lens) and binocular indirect ophthalmoscopy. In addition the following were noted: extent of the detachment present, position and number of breaks, status of the macula, presence of PVR, mobility of retina and presence of any peripheral retinal degenerations, and fundus photographs of the patient (before and after surgery). RESULTS: Risk factors for retinal detachment included myopia in 7 eyes (23.3%), prior cataract surgery in 10 eyes (33.3%), peripheral retinal degeneration in 3 eyes (10%) and traction with new vessels in 1 eye (3.3%). Eighteen eyes (60%) presented with macula off while 12 eyes (40%) presented with macula partly or completely attached. Visual acuity at presentation was <3/60 in 16 eyes. Following surgery, retina was attached in 28 eyes (93.3%) and remained detached in 2 eyes (6.7%). Visual acuity after surgery was <3/60 in 12 eyes.Visual acuity improved in 13 eyes (43.3%), remained the same in 16 eyes (53.3%) and worsened in 1 eye (3.3%). CONCLUSION: Myopia and prior cataract surgery are important risk factors for Rhegmatogenous Retinal Detachment. Majority of patients in this setting presented late with Rhegmatogenous Retinal Detachment and this was responsible for relatively poor visual outcomes despite good anatomical results after surgery. Proper screening of eyes at risk and education of patients is important for preventing visual loss due to retinal detachment. PMID- 25121048 TI - Tryptophan hydroxylase 2 gene polymorphism in anxiety and depressive disorder in kashmiri population. AB - BACKGROUND: The gene of tryptophan hydroxylase is widely recognized as a major candidate gene in many psychiatric disorders. However, no study has been done which investigates tryptophan hydroxylase 2 gene polymorphism in anxiety and depressive disorders in Kashmiri population (India). OBJECTIVES: To study tryptophan hydroxylase 2 (TPH2) C 11993 A gene polymorphism in anxiety and depressive disorders. METHOD: Sixty patients of depression disorder, 60 patients of anxiety disorder and 40 unrelated healthy volunteers (control) were studied in a case control design. Polymorphism was determined using polymerase chain reaction (PCR) and agarose gel electrophoresis after digestion with HAP II enzyme. Genotypes and allele frequencies were compared using Chi-square tests, Fischer's exact test, odds ratio, 95% confidence interval (C.I) and p-value of <0.05 was considered to be statistical significant. RESULTS: The mean age +/- SD of anxiety, depression and control group was 32.73+/-10.99, 32.20+/-10 and 29.75+/-10.12 respectively and the difference was found to be statistically non significant (p=0.349).The mean HAM-A (Hamilton rating scale for anxiety) score and HAM-D (Hamilton rating scale for depression) score was high in both groups (anxiety and depression) and found to be statistically significant (p=0.001).Depression group had AA genotype (55.2%) than control (37.5%) and was found to be statistically non significant (p=0.890).Comparison of allelic frequency revealed no association of A allele in anxiety group (76.67%) compared with control (75.5%) and was found to be statistically non significant (p= 0.866), OR 1.09 (0.56-2.11). CONCLUSION: TPH2C 11993 A gene was not found to be associated with major depressive disorder (MDD) and anxiety disorder in Kashmiri population. PMID- 25121049 TI - Role of information communication technology in higher education: learners perspective in rural medical schools. AB - BACKGROUND: Higher education has undergone profound transformation due to recent technological advancements. Resultantly health profession students have a strong base to utilize information technology for their professional development. Studies over recent past reflect a striking change in pattern of technology usage amongst medical students expanding prospects exponentially by e-books, science apps, readymade power-point presentations, evidence based medicine, Wikipedia, etc. Aim & Objectives: The study was undertaken with an aim to explore the general perceptions of medical students and faculties about the role of Information Communication Technology in higher education and to gauge student's dependence on the same for seeking knowledge and information. STUDY DESIGN: Cross sectional, mixed research design. MATERIALS AND METHODS: The study was conducted in Department of Physiology, Datta Meghe Institute of Medical Sciences (Deemed University). Study population included students (n=150) and teaching faculty (n=10) of I(st) phase of medical curriculum. The survey questionnaire (10 closed ended and 5 open ended items) and Focus group discussion (FGD) captured the perceptions and attitudes of students and faculties respectively regarding the role and relevance of technology in higher education. OBSERVATIONS AND RESULTS: Quantitative analysis of closed ended responses was done by percentage distribution and Qualitative analysis of open ended responses and FGD excerpts was done by coding and observing the trends and patterns respectively. Overall the observations were in favour of increasing usability and dependability on technology as ready reference tool of subject information. Learners valued text books and technology almost equally and regarded computer training as a desirable incorporation in medical curriculum. CONCLUSION: Role of technology in education should be anticipated and appropriate measures should be undertaken for its adequate and optimum utilization by proper training of students as well as facilitators. PMID- 25121050 TI - Dermatology Specific Quality of Life in Vitiligo Patients and Its Relation with Various Variables: A Hospital Based Cross-sectional Study. AB - INTRODUCTION: Vitiligo is an acquired, idiopathic skin disease characterized by progressive loss of the inherited skin color. Vitiligo has a special significance to patients in our country because depigmentation is obvious on dark skin and due to the enormous stigma that the disease carries. MATERIALS AND METHODS: One hundred vitiligo patients aged more than 18 years were included in our hospital based study depending on inclusion and exclusion criteria. All the patients were asked to fill a validated Hindi version of DLQI questionnaire. DLQI scores and its interpretation were recorded separately. correlation of DLQI Scores with different variables like age, body surface area, duration of disease and socioeconomic status were studied using Pearson's correlations. Mean DLQI scores were also compared between different groups. RESULTS: Male and female patient were statistically similar in all variables, like their age, BSA of the involvement and DLQI score. DLQI interpretation showed that out of 100 patients of vitiligo, 16 felt no effect of vitiligo on their quality of life while 84 patients reported small to very large effect on their quality of life. Out of this 84, 37 felt small effects, 21 felt moderate effect and rest 26 felt very large effect on their quality of life. There was no significant difference among the different groups mentioned except very large effect on quality of life seen significantly more in unmarried patients compared to married one. CONCLUSION: Vitiligo although a cosmetic disease without any symptoms, it carry a significant social stigma especially in Indian society. Data interpretation in this study indicates that vitiligo affects QOL in majority of vitiligo patients and such patients require more aggressive and empathic attitude from a dermatologist to cure/improve this so called chronic cosmetic disease. PMID- 25121051 TI - Pretibial Myxedema Associated with Euthyroid Hashimoto's Thyroiditis: A Case Report. AB - Pretibial myxedema (PM) is an infiltrative dermopathy which is seen in grave's disease. It is also associated with hypothyroidism, but is infrequently seen in Hashimoto's thyroiditis. Lesions are seen commonly over pretibial region as non pitting oedema or with a plaque morphology. Heat shock protein (HSP) has been reported to be expressed by fibroblasts present at affected site, which cause lesions of PM. Histopathology differentiates it from other dermatoses. Lesions usually resolve spontaneously, but therapies like potent topical steroids, intralesional steroids, gamma globulin, pentoxifylline, surgery and radiotherapy are indicated. Here, a case of PM with euthyroid Hashimoto's thyroiditis has been reported, which was proven by histopathology. PMID- 25121052 TI - Anything Rare is Possible: Letrozole Induced Eczematous Skin Eruption. AB - Letrozole is used as first line drug in postmenopausal women with early-stage or advanced hormone-sensitive breast cancer. Letrozole has favourable tolerability profile when administered once daily and significant adverse reactions occur rarely. The objective of this report is to describe a case of eczematous skin eruption that occurred during letrozole treatment. A 61-year-old female patient was admitted with lump in the left breast. FNAC, HPE were done and the patient was diagnosed to have invasive ductal breast carcinoma. After a month of completing CT and EBRT, the patient was given 2.5 mg OD tab. letrozole at night. She developed itchy skin lesions over the right thigh that later generalised, at 6- weeks of treatment. The lesion has been defined as eczematous moderate to severe drug eruption. These lesions were attributed to letrozole therapy and recurred within 24h after rechallenge. Drug eruption is associated with many drugs but this is the first such report with letrozole. We suggest of being aware of such reactions during letrozole usage. PMID- 25121053 TI - Prevalence of Rubber Dam Usage during Endodontic Procedure: A Questionnaire Survey. AB - AIM: To determine the prevalence and frequency of rubber dam usage for endodontic procedures among general practitioners, specialized practitioners, undergraduate final year students and Endodontists in the state of Odisha, India. METHODOLOGY: A pre-piloted questionnaire was distributed among 737 subjects. Dentists and final year students were surveyed in relation to their prevalence of rubber dam usage. STATISTICAL ANALYSIS USED: Chi-square/ Fisher Exact tests have been used to find the significance of study parameters on categorical scale between two or more groups. RESULTS: Overall response rate was 71%. While about 94% of the subjects knew the use of rubber dam, 30% have used it for root canal cases and 23% use them for all cases of root canal treatment. Use of rubber dam was 15.4% in paediatric patients and 34.4% in adult patients. 68% of subjects received knowledge about rubber dam usage in undergraduate school. 75% felt that rubber dam should be compulsory before endodontic treatment & 90% were willing to gain knowledge through training and continuing dental education programs. CONCLUSION: Whilst rubber dam is used frequently for root canal treatment than operative treatment, in the present survey there is a low prevalence of its usage during endodontic therapy. This presents quality issues, as well as medico-legal and safety concerns for the professional and patients alike. Greater emphasis should be placed on the advantages of using rubber dam in clinical dentistry at dental school and through continuing dental education for practitioners to update their knowledge. PMID- 25121054 TI - Comparison of coronally advanced and semilunar coronally repositioned flap for the treatment of gingival recession. AB - BACKGROUND: Gingival Recession (GR) occurs in population with low oral hygiene levels. Root coverage may be achieved by a number of surgical techniques, including pedicle gingival grafts, free grafts, connective tissue grafts, gtr may also be used. The objective of the present study is to compare the clinical outcomes of the Semilunar Coronally Repositioned Flap (SCRF) and Coronally Advanced Flap (CAF) procedure in the treatment of miller's class I gingival recession defects in maxillary teeth. MATERIALS AND METHODS: Twenty systemically healthy patients, with isolated miller's class 1 gingival recessions, were selected and allocated randomly into two groups, Group I and Group II with 10 patients in each. In Group I, the patients were treated with coronally advanced flap procedure with sling sutures, whereas in Group II, patients were treated with semilunar coronally repositioned flap without sutures. RESULTS: Descriptive statistical analysis has been carried out in the present study. RESULTS on continuous measurements are presented on Mean +/- SD. Significance is assessed at 5 % level of significance. Student t-test (two tailed, dependent) has been used to find the significance of study parameters between baseline - 3 months and baseline - 6 months, 90% Confidence interval for mean has been computed. CONCLUSION: CAF provides consistently better results than SCRF With all other parameters, such as clinical attachment levels, percentage of root coverage and complete root coverage and esthetics were taken into account, caf was found to be superior. In contrary to this, there is significant increase in width of keratinized tissue in scrf group. PMID- 25121055 TI - Grading of Extraction and Its Relationship with Post-operative Pain and Trismus, along with Proposed Grading for Trismus. AB - BACKGROUND: Extraction of mandibular third molars are somewhat a matter of interest because of its malpositioning , curved roots, proximity to vital structures due to this the procedure is often associated with post operative complications like pain and trismus. The extraction of third molar was classified in four grads according to the difficulty of the procedure. AIMS: The purpose of this paper is to find any significant relationship between grading of extraction and post operative complications like pain and trismus. MATERIALS AND METHODS: A total number of 180 patients need to go for extraction of third molar was included in the study. The variables taken into account were grading of extraction, pain six hour post operatively trismus one day after extraction, and trismus five day after extraction. The four grades of extractions as described by Parent in 1974 were statistically analyzed by computing pearson product moment correlation coefficient with post operative pain and trismus first and fifth day to find any co relation between them. RESULTS: The grading of extraction was found significantly correlated with post operative pain, trismus one day after and fifth day of surgery. PMID- 25121056 TI - The role and efficacy of herbal antimicrobial agents in orthodontic treatment. AB - AIMS: To assess the effect of herbal antimicrobial agents on Streptococcus mutans count in biofilm formations during orthodontic treatment. MATERIALS AND METHODS: We calculated the growth inhibition of oral bacteria in the orthodontic appliances after herbal antibacterial agents were placed in culture media. The Minimum Inhibitory Concentrations (MICs) of these agents on Streptococcus mutans growth were determined. After cultivating colonies of Streptococci in biofilm medium with these herbal antimicrobial agents and orthodontic attachments, viable cell counting was performed from the bacteria which were attached on them. Scanning electron microscopy (SEM) analysis of morphology was observed on bacterial cells which were attached to orthodontic attachments. The effects of these agents were then evaluated and recommendations were forwarded. RESULTS: There was an increase in count of Streptococcus mutans with respect to the herbal antibacterial agents. CONCLUSION: Despite the antibacterial functions of these herbal agents, there was increase in the biofilm formation caused by Streptococcus mutans to orthodontic bands, which had occurred most likely through upregulation of glucosyl transferase expression. These extracts may thus play an important role in increased bacterial attachment to orthodontic wires. Thus, this study was corroborative of an amalgamation of Ayurvedic therapy and Orthodontic treatment. PMID- 25121057 TI - The effect of different chemical surface treatments of denture teeth on shear bond strength: a comparative study. AB - BACKGROUND: The development of better cross linked acrylic resin teeth has solved the problems related to wearing and discoloration of acrylic teeth. The same cross linking at ridge lap region acts as a double edge sword as it weakens the bond between denture base and tooth. AIM OF STUDY: The purpose of study was to evaluate the effect of surface treatment on the bond strength of resin teeth to denture base resin using monomethyl methacrylate monomer and dichloromethane with no surface treatment acting as control. SETTINGS AND DESIGN: Denture base cylinder samples in wax (n=180) were made with maxillary central incisor attached at 450 (JIST 6506). These samples were randomly and equally divided into three groups of 60 each. These specimens were then flasked, dewaxed as per the standard protocol. MATERIALS AND METHODS: Before acrylization, ridge lap area was treated as follows: Group A- no surface treatment act as control, Group B treated with monomethyl methacrylate monomer, Group C treated with dichloromethane. Digitally controlled acryliser was used for acrylization as per manufacturer's instructions and shear bond strength was tested on Universal Testing Machine (Servo Hydraulic, 50kN High Strain, BISS Research). STATISTICAL ANALYSIS USED: Result was statistically analyzed with One-way analysis of variance (ANOVA) and Post-hoc ANOVA Tukey's HSD test at 5% level of significance. RESULTS: The application of dichloromethane showed increased bond strength between cross linked acrylic resin teeth and heat cure denture base resin followed by monomethyl methacrylate monomer and control group. CONCLUSION: The application of dichloromethane on the ridge lap surface of the resin teeth before packing of the dough into the mold significantly increased the bond strength between cross linked acrylic resin teeth and heat cure denture base resin. PMID- 25121058 TI - Comparison of Salivary Beta Glucuronidase Activity in Chronic Periodontitis Patients with and without Diabetes Mellitus. AB - AIM OF THE STUDY: The aim of the study was to estimate the salivary beta glucuronidase (beta) activity in patients with chronic periodontitis with and without diabetes mellitus and to evaluate the relationship between Beta Glucuronidase activity and Periodontal clinical parameters. MATERIALS AND METHODS: The study consisted of 80 patients of both sexes with age ranging from 20-60 years and they were divided into four groups. Clinical parameters such as Gingival index, Probing depth and Clinical attachment loss were measured. Salivary Beta Glucuronidase activity was measured using spectrophotometer with reagents like phenolphthalein glucuronic acid, phosphate and glycine buffer. RESULTS: The mean BG activity of Group IV (1.17 +/- 0.27) was significantly higher than mean BGA levels of Group I, II, III. The p-value was < 0.05. The mean BGA levels of Group III (0.78 +/- 0.17) was significantly higher than mean BGA levels of Group I, Group II at 5 % level. There was a significant positive linear relationship between salivary beta Glucuronidase level and Probing Depth, clinical attachment level in the experimental Groups. CONCLUSION: The salivary beta Glucuronidase level was higher in Diabetic patients with periodontitis than nondiabetic periodontitis patients. PMID- 25121059 TI - Chlorhexidine chip in the treatment of chronic periodontitis - a clinical study. AB - AIM: The aim of this study was to clinically evaluate the use of biodegradable chlorhexidine chip when used as an adjunct to scaling and root planing (SRP) in the treatment of moderate to severe periodontitis patients. The study also intended to compare the combined therapy (SRP and Chlorhexidine chip) with chlorhexidine chip alone in individuals with periodontitis. MATERIALS AND METHODS: Fifteen patients with three sites having a probing depth of 5-8mm were considered for the study. Sites were numbered 1, 2, 3 randomly. The clinical parameters assessed were the Plaque Index (PI), gingival index (GI), Bleeding on probing (BOP), Clinical attachment level (CAL) and Probing pocket depth (PPD). Following baseline evaluation, on two sites scaling and root planing (SRP) was performed, no treatment was carried out in the third site. Chlorhexidine chips were placed on one site with SRP and another without SRP. A periodontal pack was placed on the site to prevent dislodgement of the CHX chip. Clinical parameters were recorded at baseline, one month and three months. Duration of the study was for three months. STATISTICAL ANALYSIS: T-test and Analysis of variance (ANOVA) has been carried out in the present study. RESULTS: All three groups presented with an improvement in the clinical parameters compared to baseline. There was no statistically significant difference between the SRP and SRP + CHIP group in all parameters. There was a significant difference when these two groups were compared to the chip alone group. The mean reductions in PPD were 2.8mm (SRP group), 2.6 (SRP+CHIP group), 0.8 (chip alone group) The mean gain in CAL were 2.8mm (SRP group), 2.5 (SRP+CHIP group), 0.7 (chip alone group). Reduction in bleeding on probing were significant for the SRP and SRP +CHIP group but not for the chip alone group. CONCLUSION: The CHX chip did not provide any clinical benefit beyond that achieved with conventional scaling and rootplaning after a three month period. PMID- 25121061 TI - Ankyloglossia among children of regular and special schools in karnataka, India: a prevalence study. AB - BACKGROUND: Tongue-tie (more formally known as ankyloglossia) is a congenital anomaly characterized by an abnormally short lingual frenulum, which may restrict the mobility of the tongue tip impairing its ability to fulfil its functions. Ankyloglossia is uncommon, but not rare. Incidence figures reported in the literature vary widely, ranging from 0.02% to 4.8%. Incidences of upto 10.7% have been reported. Since the literature provides no uniformity of information with regard to the incidence of tongue tie. The aim of this study was to evaluate the occurrence of tonguetie in general population and mentally challenged population, measure the grades of tongue-tie and also to determine the relations of gender with tongue-tie. MATERIALS AND METHODS: Seven hundred school children in the age group of 9-17 years were examined for the presence of tongue-tie, 350 from regular schools and 350 from special schools. The presence of tongue-tie was evaluated, measured and graded into grades 1 to 5 according to KOTLOW's method and data subjected to statistical analysis. RESULTS: Significantly higher incidence of 16.4% population having tongue-tie was identified, of which 18.57% were from general schools and 13.71% from special schools but the differences were not statistically significant. Males showed greater incidence than females and grades I, II, III were more predominantly seen than grade IV, but the differences were not significant statistically. CONCLUSION: Diagnostic criteria and definitive classifying systems are needed to allow for further comparative studies. PMID- 25121060 TI - Effect of Platelet-Rich-Plasma (PRP) and Implant Surface Topography on Implant Stability and Bone. AB - PURPOSE: To evaluate the effect of Platelet-Rich-Plasma (PRP) and different implant surface topography on implant stability and bone levels around immediately loaded dental implants. MATERIALS AND METHODS: Dental implants were placed in subjects divided into two groups and four subgroups on basis of implant treatment with PRP and implant surface topography used. A total of 30 implants were placed, 15 in each group. For PRP group, implants were placed after surface treatment with PRP. Temporization was done within two weeks and final prosthesis was given after three months. Implant stability was measured with Periotest at baseline, one month and three months. Bone height was measured on mesial & distal side on standardized IOPA x-rays. RESULTS: A statistically significant difference was noticed in implant stability with PRP at baseline. The effect of PRP on bone height changes was not statistically significant. A synergistic effect of PRP and square thread-form was observed on improved implant stability and bone levels; however, no such effect is seen with PRP and reverse buttress thread-form. CONCLUSION: Within the limitation of this study, enhancement on implant stability and bone healing was observed with PRP treated implant surfaces, and with use of implant with square thread-form. PMID- 25121062 TI - Decontamination methods used for dental burs - a comparative study. AB - AIMS AND OBJECTIVES: Infection control and modes of sterilizations are the key factors to avoid cross transmission of infection in the field of dentistry. Transmission of disease or infection is noted with improper sterilization of reused instruments. Dental burs are the most important tool in any endodontic or conservative procedures of teeth involving tooth contouring, restorative filling procedures and endodontic procedures. Hence, the present study is undertaken to assess the efficacy of different methods of sterilization or decontamination which are routinely used in dental clinics. MATERIALS AND METHODS: For the present study 96 round diamond burs were selected and divided into 6 groups. These burs were used for the access cavity preparation to get contamination and subjected for bacteriological culture. After getting base line date burs were subjected to manual scrubbing, hot air oven, glass bead sterilizer, ultrasonic cleaner and autoclave to get post decontamination data. RESULTS: The study revealed that mean colony forming units/ml of Streptococcus mutans decreased maximum for autoclave with 80% reduction, for Lactobacilli 76% reduction and for Candida albicans maximum reduction seen for glass bead sterilizer with 74%. CONCLUSION: Findings of our study revealed that none of the methods used were found to be absolutely efficacious in the decontamination of dental burs. However, among the experimental groups used in the present study, autoclave was found to be the relatively best method. PMID- 25121063 TI - Polarizing and light microscopic analysis of mineralized components and stromal elements in fibrous ossifying lesions. AB - INTRODUCTION: Fibro-osseous lesions, along with few reactive lesions of the jaws exhibit an overlapping histo-morphologic spectrum with respect to the nature of calcifications and stromal components. This causes difficulty in assessing the origin, pathogenesis and diagnosis of these lesions. AIM: The present study analyses the mineralized components, cellularity, stromal density and stromal composition (nature of collagen, presence of elastic and oxytalan fibres) in cases of ossifying fibroma (OF), fibrous dysplasia (FD) and peripheral ossifying fibroma (POF). MATERIALS AND METHODS: The study included a histochemical evaluation of six cases each of FD, OF and POF. Five consecutive sections of each case were stained with hematoxylin and eosin, picrosirius red (to assess maturation of fibres in polarizing light), van Gieson (for area fraction and collagen density) and aldehyde fuchsin (for elastic and oxytalan fibres) respectively. RESULTS: Significantly higher amounts of mature bone were seen in FD while cementicles having microlamellar pattern were predominant in OF and POF (p < 0.001). Area fraction, collagen density and immature stromal fibre content was higher in POF followed by FD and OF (p= 0.039). Oxytalan and elastic fibres were absent in FD. CONCLUSION: Higher cellularity of the stroma in OF was indicative of its neoplastic behaviour. Higher composition of oxytalan and elastic fibres in OF and POF supports their periodontal ligament origin. FD was distinct with more mature fibres in a lamellated bone and absence of oxytalan fibres. PMID- 25121064 TI - Combating nasal septum deviation in le fort 1 orthognathic surgery complications, with submental intubation. AB - INTRODUCTION: Orthognathic Le Fort 1 osteotomy, a surgical procedure performed to correct the aesthetics of mid face. Some of the complications of this surgery are hemorrhage, loss of sensation due to facial nerve damage, nasal septum deviation leading to crooked nose and snoring. Nasal septum deviation is the most common complication and one of the most noticeable complications that is developed during the Le Fort 1 osteotomy. AIM: To ascertain that Submental Intubation in Orthognathic Le Fort 1 Osteotomy combats Nasal septum Deviation. MATERIALS AND METHODS: Medical records and clinical data of 32 patients who underwent orthognathic Le Fort 1 Osteotomy under submental orotracheal intubation were analyzed to understand if nasal septum deviation and other complications of Le Fort 1 Osteotomy occurred in such cases based on 6 parameters. RESULTS: No complications of nasal septum deviation or other complications that's associated with orthognathic Le Fort 1 Osteotomy were found in the 32 cases that were analyzed. DISCUSSION: The surgeon needs to have a non-obtrusive nasal canal so as to determine the extent to which the nasal septum needs to be reduced so that it does not cause nasal septum deviation post the procedure. Submental oratracheal intubation provides the surgeon with an excellent view of the operating field, enough space for intra oral manipulation of the bone and septum for intra oral operation and control of dental occlusion. CONCLUSION: Submental intubation is a better method of intubation during Le Fort 1 osteotomy as it does not cause nasal septum deviation or other associated complications. PMID- 25121065 TI - Osteosarcoma of the jaws: case report on synchronous multicentric osteosarcomas. AB - Research has shown that osteosarcomas display high potential for metastasis to the lungs, pleurae and bones. Mandible, on the other hand, is an uncommon site for metastatic tumour cell colonization. Nevertheless, a metastatic tumour to mandible might be the first indication of an undiscovered malignancy at a distant site. This case report presents a case of a 61-year-old female patient. An osteosarcoma metastasized to her mandible shortly after the curettage of her jaw cyst. Both the metastatic osteosarcoma and the jaw cyst were confirmed by pathology. Initially, bilateral well-defined radiolucent lesions were shown in her panoramic X-ray image. Also, the diagnosis of a dentigerous cyst was made, based on histology. Two months later, a mixed radiolucent-radio opaque mass, which was confirmed as an osteosarcoma by pathology later, occupied the site of the previously enucleated dentigerous cyst, in her right mandible. Then, an identical osteosarcoma was found in the left pelvis on further doing overall radiological and pathological examinations. The pathologic hypotheses, treatment modality and follow-up of this case have also been presented. PMID- 25121066 TI - Removable partial denture supported by implants with prefabricated telescopic abutments - a case report. AB - Implants have been designed to rehabilitate edentulous patients with fixed prosthesis or implant supported overdentures. Implant-supported single crowns and fixed partial dentures have become successful treatment alternatives to removable and fixed partial dentures. However, it is common to have clinical situations which make it impossible to use conventional as well as implant supported fixed partial dentures. The implant supported removable partial dentures can be a treatment modality that offers the multitude of benefits of implant-based therapy biologic, biomechanical, social, and psychological to such patients. The aim of this article is to present a case report describing the fabrication and advantages of removable partial denture supported by teeth and implants for a patient with long edentulous span. The patient was satisfied with his dentures in terms of function and aesthetics. Regular follow-up visits over a period of three years revealed that the periodontal condition of remaining natural dentition and peri-implant conditions were stable. There was no evidence of excessive residual ridge resorption or mobility of the teeth, nor were any visible changes in the bone levels of the natural teeth or implants noted on radiographs. PMID- 25121067 TI - Diagnostic CBCT in Dentigerous Cyst with Ectopic Third Molar in the Maxillary Sinus-A Case Report. AB - Dentigerous cyst is the second most common odontogenic cyst after radicular cyst. This report describes a case of a dentigerous cyst associated with an impacted maxillary third molar. Patient presented with foul smelling discharge through nose and oral cavity. Cone beam computed tomography revealed maxillary third molar displaced to lateral wall of the nose and a unilocular radiolucency obliterating the entire maxillary sinus. A provisional diagnosis of infected dentigerous cyst was made. The cyst was enucleated along with removal of third molar. Histopathological examination confirmed the diagnosis of dentigerous cyst. The patient recovery was uneventful. PMID- 25121068 TI - A simplified technique for fabrication of orbital prosthesis. AB - Eye is a vital organ not only for vision, but also an important component of facial expression, and over-all personality of a person. Loss of eye, apart from leading to impaired vision has a crippling effect on the psychology of the patient. Prosthodontic rehabilitation of such cases includes fabrication of prosthesis by acrylic resin, silicone and implants. However, not all patients are willing to use implants for maxillofacial rehabilitation. Therefore, a custom made orbital prosthesis serves as an affordable and satisfactory alternative. PMID- 25121069 TI - Endodontic treatment of a maxillary first molar with seven root canals confirmed with cone beam computer tomography - case report. AB - The most common configuration of the maxillary first molar is the presence of three roots and four root canals, although the presence of several other configurations have already been reported. The objective of this work is to present a rare anatomic configuration with seven root canals diagnosed during an endodontic therapy. Endodontic treatment was performed using a dental operating microscope. Exploring the grooves surrounding the main canals with ultrasonic troughing was able expose unexpected root canals. Instrumentation with files of smaller sizes and tapers was performed to prevent root physical weakness. The anatomic configuration was confirmed with a Cone Beam Computer Tomography image analysis which was able to clearly show the presence of seven root canals. An electronic database search was conducted to identify all the published similar cases and the best techniques to approach them are discussed. PMID- 25121070 TI - Expressly fabricated molar tube bases: enhanced adhesion. AB - Clinicians, Orthodontists and their patients' parents often expect the best results in the shortest time span possible. Orthodontic bonding of molar tubes has been an acceptable risk in a modern era of refined biomaterials and instrumentation. Although many orthodontists still prefer banding to bonding, it is the failure rate of the tubes on molars which accounts to an impedance in molar bonding. One of the reasons for molar attachment failures is attributed to improper adaptation of the buccal tube base with or without increased thickness of composite. Merits of banding the second molars especially when these are the terminal teeth for anchorage have been overemphasized in the literature. The present article presents a simple and relatively less time consuming technique of preparing molar tubes to be bonded on tooth surfaces which may be quite difficult to isolate especially for bonding, for example, mandibular second molars. The increased surface area of the composite scaffold helps not only in enhanced bond strength but also serves to reduce the incidence of plaque accumulation given the dexterity of invitro preparation. The removal of the occlusal part of the molar tube scaffold helps in prevention of open / raised bite tendencies. The present innovation, therefore, is not merely serendipity but a structured technique to overcome a common dilemma for the clinical orthodontist. The present dictum of banding being superior to molar tube bonding may prove to be futile with trendsetting molar attachments. It is also an established fact that bonding proves to be a lesser expensive modality when compared to banding procedures. PMID- 25121071 TI - Cleidocranial dysplasia: a case report illustrating diagnostic clinical and radiological findings. AB - Cleidocranial dysplasia (CCD) is a rare congenital defect, primarily affecting bones, undergoing intramembranous ossification. CCD presents with skeletal defects of several bones, the most striking feature of which are partial or complete absence of clavicles, late fontanels closure, and presence of open skull sutures and multiple wormian bones. These patients may be first noticed by the dentist because of the aesthetic problems or delayed eruption of teeth experienced by the patient. Here, we report a typical case of CCD in a 15-year old female who had classical diagnostic feature of this syndrome. PMID- 25121073 TI - Mural adenomatoid odontogenic tumour as anterior mandibular swelling: a diagnostic challenge. AB - Adenomatoid odontogenic tumour is an uncommon, benign, hamartomatous lesion that commonly affects the anterior maxilla and has two radiographic variants, follicular and extrafollicular where the former is more common than the latter. Here, we report a case of 15-year-old female with midline swelling of the mandible. Radiographically, impacted right permanent mandibular canine was associated with the radiolucent lesion. Dentigerous cyst was given as provisional diagnosis. However, histologically the lesion represented the features of cystic variant of Adenomatoid odontogenic tumour. PMID- 25121072 TI - Management of Dilacerated and S-shaped Root Canals - An Endodontist's Challenge. AB - The unique morphology of dilacerated and S-shaped root canals often pose utmost challenges in their endodontic management. Common causes of failures in such cases are primarily related to procedural errors such as ledges, fractured instruments, canal blockages, zip and elbow creations. Knowledge of dental anatomy and its variations is essential for the success of endodontic treatment. A clinician is required to have an insight of the morphology of tooth related to its shape, form and structure before commencing treatment. Routine periapical radiographs aids in assessing these morphological variations in the root canal system. This article gives a review of the literature and reports an interesting case of dilacerated and S-shaped root canals of adjacent teeth in the same patient. PMID- 25121075 TI - Plasma torch toothbrush a new insight in fear free dentisry. AB - Dental treatment is considered painful either because of fear or anxiety. Even though fear and anxiety could be managed; the needle pricks and the heat generated with drills are both painful and destructive to the tissues of the tooth. A new technology which can reduce the pain and destruction of the dental tissues will be of huge value. Plasma torch toothbrush fits into such criteria and when developed fully, will be able to apply for many of the dental procedures for increasing the efficiency. PMID- 25121074 TI - Palliative dental care- a boon for debilitating. AB - World Health Organization defines "palliative care" as the active total care of patients whose disease is not responding to curative treatment. Palliative care actually deals with patients at the terminal end stage of the disease. We always face a question why a dentist should be in a palliative team? What is the exact role of dentist? Dental treatment may not always be strenuous and curative, but also can focus on improving quality of life of the patient. Hence forth the present paper enlightens the importance of dentist role in palliative team. PMID- 25121076 TI - Drug therapy trials for the prevention of bronchopulmonary dysplasia: current and future targets. PMID- 25121078 TI - Epidemiology of pediatric acute respiratory distress syndrome in singapore: risk factors and predictive respiratory indices for mortality. AB - AIM: Acute respiratory distress syndrome (ARDS) represents the most severe form of acute lung injury. The aim of our study is to describe the epidemiology of pediatric ARDS in Singapore and compare the outcomes of ARDS using the following respiratory indices: PaO2/FiO2 ratio (P/F ratio), SpO2/FiO2 ratio (S/F ratio), oxygenation index (OI), and oxygen saturation index (OSI). METHODS: We examined medical records of patients admitted to the Children's Intensive Care Unit in KK Women's and Children's Hospital from 2009 to 2012. Those who fulfilled criteria for the American-European Consensus Conference definition for ARDS were identified. Demographic, clinical, and radiographic information were extracted and analyzed. RESULTS: We identified 70 patients with ARDS. Median age (interquartile range) was 6.2 (1.4, 10.4) years. The most common risk factor was pneumonia [50 (71%)]. Overall mortality was 44 (63%) patients. Thirty-two (56%) patients had an underlying chronic comorbidity; 18 (46%) were hematology-oncology conditions. Fifty-six (80%) patients had multiorgan dysfunction. Adjunct therapies used in our patients included inhaled nitric oxide [5 (7%)], prone position [22 (31%)], steroids [26 (37%)], and neuromuscular blockade [26 (37%)]. A high OI and low PF ratio after 24 h of diagnosis of ARDS were associated with mortality. From day 3 onward, all four respiratory indices appropriately differentiated survivors from non-survivors. Severity based on the S/F ratio and OSI demonstrated association with decreased ventilator free days and ICU free days. CONCLUSION: Risk factors for mortality included having an underlying comorbidity, multiorgan dysfunction, a low PF ratio, and high OI at 24 h of ARDS. Abnormal SpO2-based measurements were reliable markers of poor outcomes in pediatric ARDS. PMID- 25121080 TI - Delay in breast cancer: implications for stage at diagnosis and survival. AB - Breast cancer continues to be a disease with tremendous public health significance. Primary prevention of breast cancer is still not available, so efforts to promote early detection continue to be the major focus in fighting breast cancer. Since early detection is associated with decreased mortality, one would think that it is important to minimize delays in detection and diagnosis. There are two major types of delay. Patient delay is delay in seeking medical attention after self-discovering a potential breast cancer symptom. System delay is delay within the health care system in getting appointments, scheduling diagnostic tests, receiving a definitive diagnosis, and initiating therapy. Earlier studies of the consequences of delay on prognosis tended to show that increased delay is associated with more advanced stage cancers at diagnosis, thus resulting in poorer chances for survival. More recent studies have had mixed results, with some studies showing increased survival with longer delays. One hypothesis is that diagnostic difficulties could perhaps account for this survival paradox. A rapidly growing lump may suggest cancer to both doctors and patients, while a slow growing lump or other symptoms could be less obvious to them. If this is the case, then the shorter delays would be seen with the more aggressive tumors for which the prognosis is worse leading to reduced survival. It seems logical that a tumor that is more advanced at diagnosis would lead to shorter survival but the several counter-intuitive studies in this review show that it is dangerous to make assumptions. PMID- 25121077 TI - Pulmonary manifestations of primary immunodeficiency disorders in children. AB - Primary immunodeficiencies (PIDs) are inherited disorders in which one or several components of immune system are decreased, missing, or of non-appropriate function. These diseases affect the development, function, or morphology of the immune system. The group of PID comprises more than 200 different disorders and syndromes and the number of newly recognized and revealed deficiencies is still increasing. Their clinical presentation and complications depend on the type of defects and there is a great variability in the relationship between genotypes and phenotypes. A variation of clinical presentation across various age categories is also presented and children could widely differ from adult patients with PID. Respiratory symptoms and complications present a significant cause of morbidity and also mortality among patients suffering from different forms of PIDs and they are observed both in children and adults. They can affect primarily either upper airways (e.g., sinusitis and otitis media) or lower respiratory tract [e.g., pneumonia, bronchitis, bronchiectasis, and interstitial lung diseases (ILDs)]. The complications from lower respiratory tract are usually considered to be more important and also more specific for PIDs and they determinate patients' prognosis. The spectrum of the causal pathogens usually demonstrates typical pattern characteristic for each PID category. The respiratory signs of PIDs can be divided into infectious (upper and lower respiratory tract infections and complications) and non-infectious (ILDs, bronchial abnormalities - especially bronchiectasis, malignancies, and benign lymphoproliferation). Early diagnosis and appropriate therapy can prevent or at least slow down the development and course of respiratory complications of PIDs. PMID- 25121079 TI - Existing data analysis in pediatric critical care research. AB - Our objectives were to review and categorize the existing data sources that are important to pediatric critical care medicine (PCCM) investigators and the types of questions that have been or could be studied with each data source. We conducted a narrative review of the medical literature, categorized the data sources available to PCCM investigators, and created an online data source registry. We found that many data sources are available for research in PCCM. To date, PCCM investigators have most often relied on pediatric critical care registries and treatment- or disease-specific registries. The available data sources vary widely in the level of clinical detail and the types of questions they can reliably answer. Linkage of data sources can expand the types of questions that a data source can be used to study. Careful matching of the scientific question to the best available data source or linked data sources is necessary. In addition, rigorous application of the best available analysis techniques and reporting consistent with observational research standards will maximize the quality of research using existing data in PCCM. PMID- 25121082 TI - Hurricane Sandy: How Did We Do? Assessing a Manhattan Hospital's Response. PMID- 25121081 TI - Evaluation of capacity-building program of district health managers in India: a contextualized theoretical framework. AB - Performance of local health services managers at district level is crucial to ensure that health services are of good quality and cater to the health needs of the population in the area. In many low- and middle-income countries, health services managers are poorly equipped with public health management capacities needed for planning and managing their local health system. In the south Indian Tumkur district, a consortium of five non-governmental organizations partnered with the state government to organize a capacity-building program for health managers. The program consisted of a mix of periodic contact classes, mentoring and assignments and was spread over 30 months. In this paper, we develop a theoretical framework in the form of a refined program theory to understand how such a capacity-building program could bring about organizational change. A well formulated program theory enables an understanding of how interventions could bring about improvements and an evaluation of the intervention. In the refined program theory of the intervention, we identified various factors at individual, institutional, and environmental levels that could interact with the hypothesized mechanisms of organizational change, such as staff's perceived self-efficacy and commitment to their organizations. Based on this program theory, we formulated context-mechanism-outcome configurations that can be used to evaluate the intervention and, more specifically, to understand what worked, for whom and under what conditions. We discuss the application of program theory development in conducting a realist evaluation. Realist evaluation embraces principles of systems thinking by providing a method for understanding how elements of the system interact with one another in producing a given outcome. PMID- 25121084 TI - Where India stands in malaria elimination? PMID- 25121083 TI - Discharge beta-Blocker Use and Race after Coronary Artery Bypass Grafting. AB - INTRODUCTION: The use of discharge beta-blockers after cardiac surgery is associated with a long-term mortality benefit. beta-Blockers have been suggested to be less effective in black cardiovascular patients compared with whites. To date, racial differences in the long-term survival of coronary artery bypass grafting (CABG) patients who receive beta-blockers at discharge have not been examined. METHODS: A retrospective cohort study was conducted on patients undergoing CABG between 2002 and 2011. Long-term survival was compared in patients who were and who were not discharged with beta-blockers. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. P-for-interaction between race and discharge beta-blocker use was computed using a likelihood ratio test. RESULTS: A total of 853 (88%) black (n = 970) and 3,038 (88%) white (n = 3,460) patients had a history of beta-blocker use at discharge (N = 4,430). Black patients who received beta-blockers survived longer than those not receiving beta-blockers and the survival advantage was comparable with white patients (black, adjusted HR = 0.33, 95% CI = 0.23-0.46; white, adjusted HR = 0.48, 95% CI = 0.39-0.58; p-for-interaction = 0.74). Among patients discharged on beta-blockers, we did not observe a long-term survival advantage for white compared with black patients (HR = 1.2, 95% CI = 0.95-1.5). CONCLUSION: beta-Blocker use at discharge was associated with a survival advantage among black patients after CABG and a similar association was observed in white patients. PMID- 25121085 TI - Problems and their solutions in genetic counseling education in Japan. AB - With the expansion of novel chromosome testing, a career as a certified genetic counselor has been gathering a lot of attention. However, few people certified as a genetic counselor after completing postgraduate courses are able to find employment as a genetic counselor, and their salaries are quite low. It is also questionable whether or not such newly graduated genetic counselors, who have limited life experience and knowledge, can fully understand family issues and properly perform counseling sessions. To address these issues, a wide range of education and training may be necessary. In this study, we examined current problems in genetic counseling education in Japan, and proposed effective measures to address these problems. Toward creating a new society, we are currently establishing a national qualification system and cultivating qualified professionals capable of providing patients with accurate information on chromosome and genetic testing. In addition, these professionals could encourage younger generations to have an interest in genetic counseling. I also hope that these professionals will work not only in Japan but all over the world. PMID- 25121086 TI - Novel TPP-riboswitch activators bypass metabolic enzyme dependency. AB - Riboswitches are conserved regions within mRNA molecules that bind specific metabolites and regulate gene expression. TPP-riboswitches, which respond to thiamine pyrophosphate (TPP), are involved in the regulation of thiamine metabolism in numerous bacteria. As these regulatory RNAs are often modulating essential biosynthesis pathways they have become increasingly interesting as promising antibacterial targets. Here, we describe thiamine analogs containing a central 1,2,3-triazole group to induce repression of thiM-riboswitch dependent gene expression in different E. coli strains. Additionally, we show that compound activation is dependent on proteins involved in the metabolic pathways of thiamine uptake and synthesis. The most promising molecule, triazolethiamine (TT), shows concentration dependent reporter gene repression that is dependent on the presence of thiamine kinase ThiK, whereas the effect of pyrithiamine (PT), a known TPP-riboswitch modulator, is ThiK independent. We further show that this dependence can be bypassed by triazolethiamine-derivatives that bear phosphate mimicking moieties. As triazolethiamine reveals superior activity compared to pyrithiamine, it represents a very promising starting point for developing novel antibacterial compounds that target TPP-riboswitches. Riboswitch-targeting compounds engage diverse endogenous mechanisms to attain in vivo activity. These findings are of importance for the understanding of compounds that require metabolic activation to achieve effective riboswitch modulation and they enable the design of novel compound generations that are independent of endogenous activation mechanisms. PMID- 25121087 TI - N-alkynyl derivatives of 5-fluorouracil: susceptibility to palladium-mediated dealkylation and toxigenicity in cancer cell culture. AB - Palladium-activated prodrug therapy is an experimental therapeutic approach that relies on the unique chemical properties and biocompatibility of heterogeneous palladium catalysis to enable the spatially-controlled in vivo conversion of a biochemically-stable prodrug into its active form. This strategy, which would allow inducing local activation of systemically administered drug precursors by mediation of an implantable activating device made of Pd(0), has been proposed by our group as a way to reach therapeutic levels of the active drug in the affected tissue/organ while reducing its systemic toxicity. In the seminal study of such an approach, we reported that propargylation of the N1 position of 5-fluorouracil suppressed the drug's cytotoxic properties, showed high stability in cell culture and facilitated the bioorthogonal restoration of the drug's pharmacological activity in the presence of extracellular Pd(0)-functionalized resins. To provide additional insight on the properties of this system, we have investigated different N1-alkynyl derivatives of 5-fluorouracil and shown that the presence of substituents near the triple bond influence negatively on its sensitivity to palladium catalysis under biocompatible conditions. Comparative studies of the N1 vs. the N3-propargyl derivatives of 5-fluorouracil revealed that masking each or both positions equally led to inactive derivatives (>200-fold reduction of cytotoxicity relative to the unmodified drug), whereas the depropargylation process occurred faster at the N1 position than at the N3, thus resulting in greater toxigenic properties in cancer cell culture. PMID- 25121088 TI - Associations of CTLA4 Gene Polymorphisms with Graves' Ophthalmopathy: A Meta Analysis. AB - Many studies have established that T-lymphocyte antigen-4 (CTLA4) is a susceptible gene for Graves' disease (GD). Also many studies showed the association between the CTLA4 exon-1 49A/G polymorphism and the risk of developing Graves' ophthalmopathy (GO) in GD patients. But those results were inconsistent. In recent years many new studies were published which helped to shed light on the relationship of CTLA4 SNP49 with GO. So we performed the meta analysis to explore the association between the SNP49 and GO susceptibility in GD patients. Studies up to February 29, 2012, were searched by using PubMed. The odds ratio was used to evaluate the strength of the association. Altogether 12 case-control studies involving 2,505 participants were included in the meta analysis. Results showed that the G allele was related to the increased risk of GO compared with the A allele under allelic genetic model (OR = 1.14, 95% CI: 1.14-1.72, P = 0.001) in European subgroup. No publication bias was detected. Our results showed that the SNP49 polymorphism of CTLA4 gene was related to increased risk of GO. PMID- 25121089 TI - Comparative Analysis of Glycogene Expression in Different Mouse Tissues Using RNA Seq Data. AB - Glycogenes regulate a wide array of biological processes in the development of organisms as well as different diseases such as cancer, primary open-angle glaucoma, and renal dysfunction. The objective of this study was to explore the role of differentially expressed glycogenes (DEGGs) in three major tissues such as brain, muscle, and liver using mouse RNA-seq data, and we identified 579, 501, and 442 DEGGs for brain versus liver (BvL579), brain versus muscle (BvM501), and liver versus muscle (LvM442) groups. DAVID functional analysis suggested inflammatory response, glycosaminoglycan metabolic process, and protein maturation as the enriched biological processes in BvL579, BvM501, and LvM442, respectively. These DEGGs were then used to construct three interaction networks by using GeneMANIA, from which we detected potential hub genes such as PEMT and HPXN (BvL579), IGF2 and NID2 (BvM501), and STAT6 and FLT1 (LvM442), having the highest degree. Additionally, our community analysis results suggest that the significance of immune system related processes in liver, glycosphingolipid metabolic processes in the development of brain, and the processes such as cell proliferation, adhesion, and growth are important for muscle development. Further studies are required to confirm the role of predicted hub genes as well as the significance of biological processes. PMID- 25121090 TI - New acquisition protocol of 18F-choline PET/CT in prostate cancer patients: review of the literature about methodology and proposal of standardization. AB - PURPOSE: (1) To evaluate a new acquisition protocol of (18)F-choline (FCH) PET/CT for prostate cancer patients (PC), (2) to review acquisition (18)F-choline PET/CT methodology, and (3) to propose a standardized acquisition protocol on FCH PET/CT in PC patients. MATERIALS: 100 consecutive PC patients (mean age 70.5 years, mean PSA 21.35 ng/mL) were prospectively evaluated. New protocol consisted of an early scan of the pelvis immediately after the injection of the tracer (1 bed position of 4 min) followed by a whole body scan at one 1 hour. Early and 1 hour images were compared for interfering activity and pathologic findings. RESULTS: The overall detection rate of FCH PET/CT was 64%. The early static images of the pelvis showed absence of radioactive urine in ureters, bladder, or urethra which allowed a clean evaluation of the prostatic fossae. Uptake in the prostatic region was better visualized in the early phase in 26% (7/30) of cases. Other pelvic pathologic findings (bone and lymph nodes) were visualized in both early and late images. CONCLUSION: Early (18)F-choline images improve visualization of abnormal uptake in prostate fossae. All pathologic pelvic deposits (prostate, lymph nodes, and bone) were visualized in both early and late images. PMID- 25121091 TI - Effects of converting tacrolimus formulation from twice-daily to once-daily in liver transplantation recipients. AB - Typically, tacrolimus is administrated twice daily. Prolonged-release tacrolimus is the once-daily formulation and may be more convenient for patients. Experience with the administration of the once-daily formulation is still limited. This study enrolled 210 liver transplant recipients who had stable liver function and converted tacrolimus from a twice-daily to once-daily formulation on a 1 mg to 1 mg basis. Among 210 patients, seven patients (3.3%) were withdrawn from the once daily formulation due to allergy and fatigue. For the other patients, the trough concentration after converting to the once-daily formulation was lower than that of the twice-daily formulation. Liver enzymes were mildly elevated in 3 months after formulation conversion and serum creatinine and uric acid were mildly decreased. Seven patients (3.4%) had clinical suspicion of acute rejection after the formulation conversion and three of them were caused by nonadherence. 155 patients (76.4%) experienced a more convenient life with an increase of social activity. Forty-seven patients (23.2%) experienced the convenience of once-daily formulation during overseas trips. In conclusion, tacrolimus can be safely converted from the twice-daily to the once-daily formulation for most stable liver recipients. Acute rejection may occur in a minority of patients during formulation conversion and should be carefully monitored. PMID- 25121092 TI - Expression of acetylcholine receptors by experimental rat renal allografts. AB - Chronic allograft injury (CAI) is a major cause for renal allograft dysfunction and characterized by vasculopathies, tubular atrophy, and fibrosis. We demonstrated that numerous leukocytes interact with vascular endothelial cells of allografts and produce acetylcholine, which contributes to vascular remodeling. The cholinergic system might be a promising target for the development of novel therapies. However, neither the cellular mechanisms nor the acetylcholine receptors involved in CAI are known. Kidney transplantation was performed in the Lewis to Lewis and in the Fischer-334 to Lewis rat strain combination, which is an established experimental model for CAI. Expression of nicotinic and muscarinic acetylcholine receptors mRNA was quantified in renal tissue by real-time RT-PCR on days 9 and 42 after surgery. We detected CHRNA2-7, CHRNA10, CHRNB2, CHRNB4, and CHRM1-3 mRNA in normal kidneys and in renal transplants. In contrast, CHRNA9, CHRM4, and CHRM5 mRNA remained below the threshold of detection. In renal allografts, CHRNA3 and CHRNB4 mRNA expression were dramatically reduced compared to isografts. In conclusion, we demonstrated that most acetylcholine receptor subtypes are expressed by normal and transplanted kidneys. Allograft rejection downmodulates CHRNA3 and CHRNB4 mRNA. The role of different acetylcholine receptor subtypes in the development of CAI remains to be established. PMID- 25121093 TI - Gonadal transcriptome analysis of male and female olive flounder (Paralichthys olivaceus). AB - Olive flounder (Paralichthys olivaceus) is an important commercially cultured marine flatfish in China, Korea, and Japan, of which female grows faster than male. In order to explore the molecular mechanism of flounder sex determination and development, we used RNA-seq technology to investigate transcriptomes of flounder gonads. This produced 22,253,217 and 19,777,841 qualified reads from ovary and testes, which were jointly assembled into 97,233 contigs. Among them, 23,223 contigs were mapped to known genes, of which 2,193 were predicted to be differentially expressed in ovary and 887 in testes. According to annotation information, several sex-related biological pathways including ovarian steroidogenesis and estrogen signaling pathways were firstly found in flounder. The dimorphic expression of overall sex-related genes provides further insights into sex determination and gonadal development. Our study also provides an archive for further studies of molecular mechanism of fish sex determination. PMID- 25121094 TI - Promoting nerve regeneration in a neurotmesis rat model using poly(DL-lactide epsilon-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly: in vitro and in vivo analysis. AB - In peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton's jelly (HMSCs), differentiated into neuroglial-like cells associated to poly (DL-lactide-epsilon-caprolactone) membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat sciatic nerve model. Results in vitro showed successful differentiation of HMSCs into neuroglial-like cells, characterized by expression of specific neuroglial markers confirmed by immunocytochemistry and by RT-PCR and qPCR targeting specific genes expressed. In vivo testing evaluated during the healing period of 20 weeks, showed no evident positive effect of HMSCs or neuroglial-like cell enrichment at the sciatic nerve repair site on most of the functional and nerve morphometric predictors of nerve regeneration although the nociception function was almost normal. EPT on the other hand, recovered significantly better after HMSCs enriched membrane employment, to values of residual functional impairment compared to other treated groups. When the neurotmesis injury can be surgically reconstructed with an end-to-end suture or by grafting, the addition of a PLC membrane associated with HMSCs seems to bring significant advantage, especially concerning the motor function recovery. PMID- 25121095 TI - Novel approach to reactive oxygen species in nontransfusion-dependent thalassemia. AB - The term Nontransfusion dependent thalassaemia (NTDT) was suggested to describe patients who had clinical manifestations that are too severe to be termed minor yet too mild to be termed major. Those patients are not entirely dependent on transfusions for survival. If left untreated, three main factors are responsible for the clinical sequelae of NTDT: ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. Reactive oxygen species (ROS) generation in NTDT patients is caused by 2 major mechanisms. The first one is chronic hypoxia resulting from chronic anemia and ineffective erythropoiesis leading to mitochondrial damage and the second is iron overload also due to chronic anemia and tissue hypoxia leading to increase intestinal iron absorption in thalassemic patients. Oxidative damage by reactive oxygen species (generated by free globin chains and labile plasma iron) is believed to be one of the main contributors to cell injury, tissue damage, and hypercoagulability in patients with thalassemia. Independently increased ROS has been linked to a myriad of pathological outcomes such as leg ulcers, decreased wound healing, pulmonary hypertension, silent brain infarcts, and increased thrombosis to count a few. Interestingly many of those complications overlap with those found in NTDT patients. PMID- 25121096 TI - TBT effects on the development of intersex (ovotestis) in female fresh water prawn Macrobrachium rosenbergii. AB - The impact of tributyltin (TBT) on the female gonad and the endocrine system in Macrobrachium rosenbergii was studied. Prawns were exposed to environmentally realistic concentrations of 10, 100, and 1000 ng/L of TBT for 6 months. Dose dependent effects were noticed in TBT exposed prawns. At 1000 ng/L TBT caused ovotestis formation (formation of male germ cells in ovary). Presence immature oocytes, fusion of developing oocytes, increase in interstitial connective tissues, and its modification into tubular like structure and abundance of spermatogonia in the ovary of TBT treated prawns. The control prawn ovary showed normal architecture of cellular organelles such as mature oocytes with type 2 yolk globules, lipid droplets, normal appearance of yolk envelop, and uniformly arranged microvilli. On the other hand, type 1 yolk globules, reduced size of microvilli, spermatogonial cells in ovary, spermatogonia with centrally located nucleus, and chromatin distribution throughout the nucleoplasm were present in the TBT treated group. Immunofluorescence staining indicated a reduction in vitellin content in ovary of TBT treated prawn. Moreover, TBT had inhibited the vitellogenesis by causing hormonal imbalance in M. rosenbergii. Thus, the present investigation demonstrates that TBT substantially affects sexual differentiation and gonadal development in M. rosenbergii. PMID- 25121097 TI - Caspase-14 expression impairs retinal pigment epithelium barrier function: potential role in diabetic macular edema. AB - We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR). Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE) dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D glucose) on caspase-14 expression in human RPE (ARPE-19) cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose (5 mM D-glucose + 25 mM L-glucose). We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing (ECIS) to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance (TER). These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema. PMID- 25121099 TI - Validity and reliability of the Bahasa Melayu version of the Migraine Disability Assessment questionnaire. AB - BACKGROUND: The study was designed to determine the validity and reliability of the Bahasa Melayu version (MIDAS-M) of the Migraine Disability Assessment (MIDAS) questionnaire. METHODS: Patients having migraine for more than six months attending the Neurology Clinic, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia, were recruited. Standard forward and back translation procedures were used to translate and adapt the MIDAS questionnaire to produce the Bahasa Melayu version. The translated Malay version was tested for face and content validity. Validity and reliability testing were further conducted with 100 migraine patients (1st administration) followed by a retesting session 21 days later (2nd administration). RESULTS: A total of 100 patients between 15 and 60 years of age were recruited. The majority of the patients were single (66%) and students (46%). Cronbach's alpha values were 0.84 (1st administration) and 0.80 (2nd administration). The test-retest reliability for the total MIDAS score was 0.73, indicating that the MIDAS-M questionnaire is stable; for the five disability questions, the test-retest values ranged from 0.77 to 0.87. CONCLUSION: The MIDAS-M questionnaire is comparable with the original English version in terms of validity and reliability and may be used for the assessment of migraine in clinical settings. PMID- 25121100 TI - Prevalence and correlation between TMD based on RDC/TMD diagnoses, oral parafunctions and psychoemotional stress in Polish university students. AB - The aim of the study was to assess the prevalence of temporomandibular disorders (TMD) and oral parafunctions, as well as their correlation with psychoemotional factors in Polish university students. The research was conducted in a group of 456 students (N = 456). The examination form comprised of two parts: survey and clinical examination. The research diagnostic criteria for temporomandibular disorders (RDC/TMD) was used in order to assess TMD. Symptoms of TMD were observed in 246 (54%) students after clinical examination. The largest group involved students with disc displacement (women: 132, 29%; men: 70, 15%). Women (164; 36%) suffered more frequently than men (82; 18%) from problems related to the stomatognathic system (P < 0.05), described themselves as easily excitable and emotionally burdened, and reported symptoms as tightness of the facial and neck muscles (P < 0.05). In 289 (64%) students intraoral symptoms concerning occlusal parafunctions were observed. In 404 (89%) examined students, nonocclusal parafunctions were recorded. A significant correlation between TMD and psychoemotional problems could be detected. TMD symptoms more often concern women. Emotional burden and excitability are factors predisposing muscular disorders. PMID- 25121098 TI - Cell death and deubiquitinases: perspectives in cancer. AB - The process of cell death has important physiological implications. At the organism level it is mostly involved in maintenance of tissue homeostasis. At the cellular level, the strategies of cell death may be categorized as either suicide or sabotage. The mere fact that many of these processes are programmed and that these are often deregulated in pathological conditions is seed to thought. The various players that are involved in these pathways are highly regulated. One of the modes of regulation is via post-translational modifications such as ubiquitination and deubiquitination. In this review, we have first dealt with the different modes and pathways involved in cell death and then we have focused on the regulation of several proteins in these signaling cascades by the different deubiquitinating enzymes, in the perspective of cancer. The study of deubiquitinases is currently in a rather nascent stage with limited knowledge both in vitro and in vivo, but the emerging roles of the deubiquitinases in various processes and their specificity have implicated them as potential targets from the therapeutic point of view. This review throws light on another aspect of cancer therapeutics by targeting the deubiquitinating enzymes. PMID- 25121101 TI - Hepatic chemerin and chemokine-like receptor 1 expression in patients with chronic hepatitis C. AB - INTRODUCTION: Chemerin seems to be involved in pathogenesis of chronic hepatitis C (CHC). Hepatic expressions of chemerin and its receptor, chemokine receptor like 1 (CMKLR1), in CHC have not been studied so far. AIM: To evaluate chemerin and CMKLR1 hepatic expression together with serum chemerin concentration in CHC patients and to assess their relationship with metabolic and histopathological abnormalities. METHODS: The study included 63 nonobese CHC patients. Transcription of chemerin and CMKLR1 was assessed by quantitative real-time PCR, while serum chemerin was assessed by enzyme-linked immunosorbent assay. RESULTS: Expression of chemerin and CMKLR1 was present in the liver of all CHC patients regardless of sex or age. This expression was not associated with necroinflammatory activity and steatosis grade, fibrosis stage, and metabolic abnormalities. There was a negative association between serum chemerin and chemerin hepatic expression (r = (-0.41), P = 0.006). CONCLUSION: The study for the first time confirmed a marked expression of chemerin and CMKLR1 in the liver of CHC patients. The study was performed using the homogenates of human liver tissue, so it is not possible to define whether hepatocytes or other cell types which are abundantly represented in the liver constitute the main source of chemerin and CMKLR1 mRNA. PMID- 25121102 TI - Fungi treated with small chemicals exhibit increased antimicrobial activity against facultative bacterial and yeast pathogens. AB - For decades, fungi have been the main source for the discovery of novel antimicrobial drugs. Recent sequencing efforts revealed a still high number of so far unknown "cryptic" secondary metabolites. The production of these metabolites is presumably epigenetically silenced under standard laboratory conditions. In this study, we investigated the effect of six small mass chemicals, of which some are known to act as epigenetic modulators, on the production of antimicrobial compounds in 54 spore forming fungi. The antimicrobial effect of fungal samples was tested against clinically facultative pathogens and multiresistant clinical isolates. In total, 30 samples of treated fungi belonging to six different genera reduced significantly growth of different test organisms compared to the untreated fungal sample (growth log reduction 0.3-4.3). For instance, the pellet of Penicillium restrictum grown in the presence of butyrate revealed significant higher antimicrobial activity against Staphylococcus (S.) aureus and multiresistant S. aureus strains and displayed no cytotoxicity against human cells, thus making it an ideal candidate for antimicrobial compound discovery. Our study shows that every presumable fungus, even well described fungi, has the potential to produce novel antimicrobial compounds and that our approach is capable of rapidly filling the pipeline for yet undiscovered antimicrobial substances. PMID- 25121103 TI - Stem cell based gene therapy in prostate cancer. AB - Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new upgraded cellular vehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using stem cells in prostate cancer include the cytosine deaminase/5 fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review the stem cell therapy in prostate cancer including its proven mechanisms and also limitations. PMID- 25121104 TI - Antidiabetic activity of Acacia tortilis (Forsk.) Hayne ssp. raddiana polysaccharide on streptozotocin-nicotinamide induced diabetic rats. AB - The present study was designed to investigate the antidiabetic activity of aqueous extract of Acacia tortilis polysaccharide (AEATP) from gum exudates and its role in comorbidities associated with diabetes in STZ-nicotinamide induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, glimepiride treated (10 mg/kg), and diabetic rats treated with 250, 500, and 1000 mg/kg dose of AEATP groups and fasting blood glucose, glycated hemoglobin, total cholesterol, triglyceride, LDL, VLDL, HDL, SGOT, and SGPT levels were measured. STZ significantly increased fasting blood glucose level, glycated hemoglobin, total cholesterol, triglyceride, LDL, VLDL, SGOT, and SGPT levels, whereas HDL level was reduced as compared to control group. After 7 days of administration, 500 and 1000 mg/kg dose of AEATP showed significant reduction (P < 0.05) in fasting blood glucose level compared to diabetic control. AEATP has also reduced total cholesterol, triglyceride, LDL, VLDL, SGOT, and SGPT levels and improved HDL level as compared to diabetic control group. Our study is the first to report the normalization of fasting blood glucose level, lipid profile, and liver enzyme in AEATP treated diabetic rats. Thus, it can be concluded that AEATP may have potentials for the treatment of T2DM and its comorbidities. PMID- 25121105 TI - Local packing density is the main structural determinant of the rate of protein sequence evolution at site level. AB - Functional and biophysical constraints result in site-dependent patterns of protein sequence variability. It is commonly assumed that the key structural determinant of site-specific rates of evolution is the Relative Solvent Accessibility (RSA). However, a recent study found that amino acid substitution rates correlate better with two Local Packing Density (LPD) measures, the Weighted Contact Number (WCN) and the Contact Number (CN), than with RSA. This work aims at a more thorough assessment. To this end, in addition to substitution rates, we considered four other sequence variability scores, four measures of solvent accessibility (SA), and other CN measures. We compared all properties for each protein of a structurally and functionally diverse representative dataset of monomeric enzymes. We show that the best sequence variability measures take into account phylogenetic tree topology. More importantly, we show that both LPD measures (WCN and CN) correlate better than all of the SA measures, regardless of the sequence variability score used. Moreover, the independent contribution of the best LPD measure is approximately four times larger than that of the best SA measure. This study strongly supports the conclusion that a site's packing density rather than its solvent accessibility is the main structural determinant of its rate of evolution. PMID- 25121106 TI - Rho/ROCK signal cascade mediates asymmetric dimethylarginine-induced vascular smooth muscle cells migration and phenotype change. AB - Asymmetric dimethylarginine (ADMA) induces vascular smooth muscle cells (VSMCs) migration. VSMC phenotype change is a prerequisite of migration. RhoA and Rho kinase (ROCK) mediate migration of VSMCs. We hypothesize that ADMA induces VSMC migration via the activation of Rho/ROCK signal pathway and due to VSMCs phenotype change. ADMA activates Rho/ROCK signal pathway that interpreted by the elevation of RhoA activity and phosphorylation level of a ROCK substrate. Pretreatment with ROCK inhibitor, Y27632 completely reverses the induction of ADMA on ROCK and in turn inhibits ADMA-induced VSMCs migration. When the Rho/ROCK signal pathway has been blocked by pretreatment with Y27632, the induction of ERK signal pathway by ADMA is completely abrogated. Elimination of ADMA via overexpression of dimethylarginine dimethylaminohydrolase 2 (DDAH2) and L arginine both blocks the effects of ADMA on the activation of Rho/ROCK and extra cellular signal-regulated kinase (ERK) in VSMCs. The expression of differentiated phenotype relative proteins was reduced and the actin cytoskeleton was disassembled by ADMA, which were blocked by Y27632, further interpreting that ADMA inducing VSMCs migration via Rho/ROCK signal pathway is due to its effect on the VSMCs phenotype change. Our present study may help to provide novel insights into the therapy and prevention of atherosclerosis. PMID- 25121108 TI - Particle-size distribution models for the conversion of Chinese data to FAO/USDA system. AB - We investigated eleven particle-size distribution (PSD) models to determine the appropriate models for describing the PSDs of 16349 Chinese soil samples. These data are based on three soil texture classification schemes, including one ISSS (International Society of Soil Science) scheme with four data points and two Katschinski's schemes with five and six data points, respectively. The adjusted coefficient of determination r (2), Akaike's information criterion (AIC), and geometric mean error ratio (GMER) were used to evaluate the model performance. The soil data were converted to the USDA (United States Department of Agriculture) standard using PSD models and the fractal concept. The performance of PSD models was affected by soil texture and classification of fraction schemes. The performance of PSD models also varied with clay content of soils. The Anderson, Fredlund, modified logistic growth, Skaggs, and Weilbull models were the best. PMID- 25121109 TI - A synchronous-asynchronous particle swarm optimisation algorithm. AB - In the original particle swarm optimisation (PSO) algorithm, the particles' velocities and positions are updated after the whole swarm performance is evaluated. This algorithm is also known as synchronous PSO (S-PSO). The strength of this update method is in the exploitation of the information. Asynchronous update PSO (A-PSO) has been proposed as an alternative to S-PSO. A particle in A PSO updates its velocity and position as soon as its own performance has been evaluated. Hence, particles are updated using partial information, leading to stronger exploration. In this paper, we attempt to improve PSO by merging both update methods to utilise the strengths of both methods. The proposed synchronous asynchronous PSO (SA-PSO) algorithm divides the particles into smaller groups. The best member of a group and the swarm's best are chosen to lead the search. Members within a group are updated synchronously, while the groups themselves are asynchronously updated. Five well-known unimodal functions, four multimodal functions, and a real world optimisation problem are used to study the performance of SA-PSO, which is compared with the performances of S-PSO and A PSO. The results are statistically analysed and show that the proposed SA-PSO has performed consistently well. PMID- 25121107 TI - Beneficial effects of adiponectin on periodontal ligament cells under normal and regenerative conditions. AB - Type 2 diabetes and obesity are increasing worldwide and linked to periodontitis, a chronic disease which is characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium. The mechanisms underlying the association of diabetes mellitus and obesity with periodontal destruction and compromised periodontal healing are not well understood, but decreased plasma levels of adiponectin, as found in diabetic and obese individuals, might be a critical mechanistic link. The aim of this in vitro study was to examine the effects of adiponectin on periodontal ligament (PDL) cells under normal and regenerative conditions, and to study the regulation of adiponectin and its receptors in these cells. Adiponectin stimulated significantly the expression of growth factors and extracellular matrix, proliferation, and in vitro wound healing, reduced significantly the constitutive tumor necrosis factor-alpha expression, and caused a significant upregulation of its own expression. The beneficial actions of enamel matrix derivative on a number of PDL cell functions critical for periodontal regeneration were partially enhanced by adiponectin. The periodontopathogen Porphyromonas gingivalis inhibited the adiponectin expression and stimulated the expression of its receptors. In conclusion, reduced levels of adiponectin, as found in type 2 diabetes and obesity, may compromise periodontal health and healing. PMID- 25121110 TI - Rhizomes help the forage grass Leymus chinensis to adapt to the salt and alkali stresses. AB - Leymus chinensis has extensive ecological adaptability and can grow well in saline-alkaline soils. The knowledge about tolerance mechanisms of L. chinensis could be base for utilization of saline-alkaline soils and grassland restoration and rebuilding. Two neutral salts (NaCl : Na2SO4 = 9 : 1) and two alkaline salts (NaHCO3 : Na2CO3 = 9 : 1) with concentration of 0, 100, and 200 mmol/L were used to treat potted 35-day-old seedlings with rhizome growth, respectively. After 10 days, the biomass and number of daughter shoots all decreased, with more reduction in alkali than in salt stress. The rhizome biomass reduced more than other organs. The number of daughter shoots from rhizome was more than from tillers. Under both stresses, Na(+) contents increased more in rhizome than in other organs; the reduction of K(+) content was more in underground than aerial tissue. Anion ions or organic acids were absorbed to neutralize cations. Na(+) content in stem and leaf increased markedly in high alkalinity (200 mmol/L), with accumulation of soluble sugar and organic acids sharply. Rhizomes help L. chinensis to adapt to saline and low alkaline stresses by transferring Na(+). However, rhizomes lost the ability to prevent Na(+) transport to aerial organs under high alkalinity, which led to severe growth inhibition of L. chinensis. PMID- 25121111 TI - Integrated navigation fusion strategy of INS/UWB for indoor carrier attitude angle and position synchronous tracking. AB - In some GPS failure conditions, positioning for mobile target is difficult. This paper proposed a new method based on INS/UWB for attitude angle and position synchronous tracking of indoor carrier. Firstly, error model of INS/UWB integrated system is built, including error equation of INS and UWB. And combined filtering model of INS/UWB is researched. Simulation results show that the two subsystems are complementary. Secondly, integrated navigation data fusion strategy of INS/UWB based on Kalman filtering theory is proposed. Simulation results show that FAKF method is better than the conventional Kalman filtering. Finally, an indoor experiment platform is established to verify the integrated navigation theory of INS/UWB, which is geared to the needs of coal mine working environment. Static and dynamic positioning results show that the INS/UWB integrated navigation system is stable and real-time, positioning precision meets the requirements of working condition and is better than any independent subsystem. PMID- 25121112 TI - The smallest spectral radius of graphs with a given clique number. AB - The first four smallest values of the spectral radius among all connected graphs with maximum clique size omega >= 2 are obtained. PMID- 25121113 TI - Long-term and short-term effects of hemodialysis on liver function evaluated using the galactose single-point test. AB - AIM: The galactose single-point (GSP) test assesses functioning liver mass by measuring the galactose concentration in the blood 1 hour after its administration. The purpose of this study was to investigate the impact of hemodialysis (HD) on short-term and long-term liver function by use of GSP test. METHODS: Seventy-four patients on maintenance HD (46 males and 28 females, 60.38 +/- 11.86 years) with a mean time on HD of 60.77 +/- 48.31 months were studied. The GSP values were compared in two groups: (1) before and after single session HD, and (2) after one year of maintenance HD. RESULTS: Among the 74 HD patient, only the post-HD Cr levels and years on dialysis were significantly correlated with GSP values (r = 0.280, P < 0.05 and r = -0.240, P < 0.05, resp.). 14 of 74 patients were selected for GSP evaluation before and after a single HD session, and the hepatic clearance of galactose was similar (pre-HD 410 +/- 254 g/mL, post HD 439 +/- 298 g/mL, P = 0.49). GSP values decreased from 420.20 +/- 175.26 g/mL to 383.40 +/- 153.97 g/mL after 1 year maintenance HD in other 15 patients (mean difference: 19.00 +/- 37.66 g/mL, P < 0.05). CONCLUSIONS: Patients on maintenance HD for several years may experience improvement of their liver function. However, a single HD session does not affect liver function significantly as assessed by the GSP test. Since the metabolism of galactose is dependent on liver blood flow and hepatic functional mass, further studies are needed. PMID- 25121114 TI - Towards dynamic remote data auditing in computational clouds. AB - Cloud computing is a significant shift of computational paradigm where computing as a utility and storing data remotely have a great potential. Enterprise and businesses are now more interested in outsourcing their data to the cloud to lessen the burden of local data storage and maintenance. However, the outsourced data and the computation outcomes are not continuously trustworthy due to the lack of control and physical possession of the data owners. To better streamline this issue, researchers have now focused on designing remote data auditing (RDA) techniques. The majority of these techniques, however, are only applicable for static archive data and are not subject to audit the dynamically updated outsourced data. We propose an effectual RDA technique based on algebraic signature properties for cloud storage system and also present a new data structure capable of efficiently supporting dynamic data operations like append, insert, modify, and delete. Moreover, this data structure empowers our method to be applicable for large-scale data with minimum computation cost. The comparative analysis with the state-of-the-art RDA schemes shows that the proposed scheme is secure and highly efficient in terms of the computation and communication overhead on the auditor and server. PMID- 25121115 TI - Displacement-based back-analysis of the model parameters of the Nuozhadu high earth-rockfill dam. AB - The parameters of the constitutive model, the creep model, and the wetting model of materials of the Nuozhadu high earth-rockfill dam were back-analyzed together based on field monitoring displacement data by employing an intelligent back analysis method. In this method, an artificial neural network is used as a substitute for time-consuming finite element analysis, and an evolutionary algorithm is applied for both network training and parameter optimization. To avoid simultaneous back-analysis of many parameters, the model parameters of the three main dam materials are decoupled and back-analyzed separately in a particular order. Displacement back-analyses were performed at different stages of the construction period, with and without considering the creep and wetting deformations. Good agreement between the numerical results and the monitoring data was obtained for most observation points, which implies that the back analysis method and decoupling method are effective for solving complex problems with multiple models and parameters. The comparison of calculation results based on different sets of back-analyzed model parameters indicates the necessity of taking the effects of creep and wetting into consideration in the numerical analyses of high earth-rockfill dams. With the resulting model parameters, the stress and deformation distributions at completion are predicted and analyzed. PMID- 25121116 TI - Narrow band region-based active contours model for noisy color image segmentation. AB - A narrow band active contour model for color image segmentation is proposed, which applies local statistics to improve the robustness against noise. The crux of our approach is to use intensity mean of local region to define the force function within a level set framework, within which a narrow band is implemented to further improve the computational efficiency. In addition, the image is segmented from channel-to-channel, which shows superior performance when the intensities of the object and background are similar. Furthermore, a multichannel segmentation combination method is used to integrate the information of multiple level sets. The proposed model has been applied to both synthetic and real images with expected results, and the comparison with the state-of-the-art approaches demonstrates the accuracy and superiority of our approach. PMID- 25121117 TI - Haematological and biochemical parameters during the laying period in common pheasant hens housed in enhanced cages. AB - The development of selected haematological and biochemical parameters during the laying period was monitored in common pheasant hens housed in an enhanced cage system. The cages were enhanced by the addition of two perches and a shelter formed by strips of cloth hanging in the corner of the cage. The results showed significant changes in the haematological and biochemical parameters monitored during egg laying. At the time when laying capacity approached a maximum, a decrease was observed (P < 0.05) in haematocrit, erythrocytes, and haemoglobin values, whereas monocytes, eosinophils, the heterophil/lymphocyte ratio, phosphorus, and calcium exhibited an increase (P < 0.05). At the end of the laying period, an increase (P < 0.05) was recorded in the count of leukocytes, heterophils, lymphocytes and basophils, the heterophil to lymphocyte ratio, and the concentrations of aspartate aminotransferase, cholesterol, phosphorus, and calcium, whereas lower values (P < 0.05) were recorded for haematocrit and plasma total protein in comparison with the values of the indicators at the beginning of the laying period. The results provide new information about dynamic changes in selected haematological and biochemical parameters in clinically healthy common pheasant hens during the laying period. PMID- 25121118 TI - Intrastrain comparison of the chemical composition and antioxidant activity of an edible mushroom, Pleurotus giganteus, and its potent neuritogenic properties. AB - Two strains of Pleurotus giganteus (commercial and wild) were tested for their ability to induce neurite outgrowth in rat pheochromocytoma (PC12) and mouse neuroblastoma-2a (N2a) cells. Treatment with the mushroom extracts resulted in neuronal differentiation and neuronal elongation, but not nerve growth factor (NGF) production. Linoleic acid (4.5-5.0%, w/w) which is a major fatty acid present in the ethanol extract promoted NGF biosynthesis when augmented with low concentration of NGF (5 ng/mL). The two strains of mushroom were found to be high in protein (154-192 g kg(-1)), total polysaccharides, phenolics, and flavonoids as well as vitamins B1, B2, and B3. The total phenolics present in the mushroom extracts were positively correlated to the antioxidant activity (free radical scavenging, ferric reducing power, and lipid peroxidation inhibition). To conclude, P. giganteus could potentially be used in well-balanced diet and as a source of dietary antioxidant to promote neuronal health. PMID- 25121119 TI - Automated detection and evaluation of swallowing using a combined EMG/bioimpedance measurement system. AB - INTRODUCTION: Developing an automated diagnostic and therapeutic instrument for treating swallowing disorders requires procedures able to reliably detect and evaluate a swallow. We tested a two-stage detection procedure based on a combined electromyography/bioimpedance (EMBI) measurement system. EMBI is able to detect swallows and distinguish them from similar movements in healthy test subjects. STUDY DESIGN: The study was planned and conducted as a case-control study (EA 1/019/10, and EA1/160/09, EA1/161/09). METHOD: The study looked at differences in swallowing parameters in general and in the event of penetration during swallows in healthy subjects and in patients with an oropharyngeal swallowing disorder. A two-stage automated swallow detection procedure which used electromyography (EMG) and bioimpedance (BI) to reliably detect swallows was developed. RESULTS: Statistically significant differences between healthy subjects and patients with a swallowing disorder were found in swallowing parameters previously used to distinguish between swallowing and head movements. Our two-stage algorithm was able to reliably detect swallows (sensitivity = 96.1%, specificity = 97.1%) on the basis of these differences. DISCUSSION: Using a two-stage detection procedure, the EMBI measurement procedure is able to detect and evaluate swallows automatically and reliably. The two procedures (EMBI + swallow detection) could in future form the basis for automated diagnosis and treatment (stimulation) of swallowing disorders. PMID- 25121121 TI - Mechanical performance and parameter sensitivity analysis of 3D braided composites joints. AB - 3D braided composite joints are the important components in CFRP truss, which have significant influence on the reliability and lightweight of structures. To investigate the mechanical performance of 3D braided composite joints, a numerical method based on the microscopic mechanics is put forward, the modeling technologies, including the material constants selection, element type, grid size, and the boundary conditions, are discussed in detail. Secondly, a method for determination of ultimate bearing capacity is established, which can consider the strength failure. Finally, the effect of load parameters, geometric parameters, and process parameters on the ultimate bearing capacity of joints is analyzed by the global sensitivity analysis method. The results show that the main pipe diameter thickness ratio gamma, the main pipe diameter D, and the braided angle alpha are sensitive to the ultimate bearing capacity N. PMID- 25121120 TI - Estimating body related soft biometric traits in video frames. AB - Soft biometrics can be used as a prescreening filter, either by using single trait or by combining several traits to aid the performance of recognition systems in an unobtrusive way. In many practical visual surveillance scenarios, facial information becomes difficult to be effectively constructed due to several varying challenges. However, from distance the visual appearance of an object can be efficiently inferred, thereby providing the possibility of estimating body related information. This paper presents an approach for estimating body related soft biometrics; specifically we propose a new approach based on body measurement and artificial neural network for predicting body weight of subjects and incorporate the existing technique on single view metrology for height estimation in videos with low frame rate. Our evaluation on 1120 frame sets of 80 subjects from a newly compiled dataset shows that the mentioned soft biometric information of human subjects can be adequately predicted from set of frames. PMID- 25121123 TI - A lower bound on the sinc function and its application. AB - A lower bound on the sinc function is given. Application for the sequence {b(n)}(n=1)(infinity) which related to Carleman inequality is given as well. PMID- 25121122 TI - Observer design for a core circadian rhythm network. AB - The paper investigates the observer design for a core circadian rhythm network in Drosophila and Neurospora. Based on the constructed highly nonlinear differential equation model and the recently proposed graphical approach, we design a rather simple observer for the circadian rhythm oscillator, which can well track the state of the original system for various input signals. Numerical simulations show the effectiveness of the designed observer. Potential applications of the related investigations include the real-world control and experimental design of the related biological networks. PMID- 25121124 TI - Electronically tunable quadrature oscillator using grounded components with current and voltage outputs. AB - The electronically tunable quadrature oscillator using a single multiple-output current controlled current differencing transconductance amplifier (MO-CCCDTA) and grounded passive components is presented. The proposed configuration uses a single MO-CCCDTA, two grounded capacitors and one grounded resistor. Two high output impedance quadrature current signals and two quadrature voltage signals with 90 degrees phase difference. The oscillation condition and oscillation frequency of the proposed quadrature oscillator are independently controllable. The use of only grounded passive components makes the proposed circuit ideal for integrated circuit implementation. PMID- 25121125 TI - Vehicle density based forwarding protocol for safety message broadcast in VANET. AB - In vehicular ad hoc networks (VANETs), the medium access control (MAC) protocol is of great importance to provide time-critical safety applications. Contemporary multihop broadcast protocols in VANETs usually choose the farthest node in broadcast range as the forwarder to reduce the number of forwarding hops. However, in this paper, we demonstrate that the farthest forwarder may experience large contention delay in case of high vehicle density. We propose an IEEE 802.11 based multihop broadcast protocol VDF to address the issue of emergency message dissemination. To achieve the tradeoff between contention delay and forwarding hops, VDF adaptably chooses the forwarder according to the vehicle density. Simulation results show that, due to its ability to decrease the transmission collisions, the proposed protocol can provide significantly lower broadcast delay. PMID- 25121126 TI - Applying dynamic priority scheduling scheme to static systems of pinwheel task model in power-aware scheduling. AB - Power-aware scheduling reduces CPU energy consumption in hard real-time systems through dynamic voltage scaling (DVS). In this paper, we deal with pinwheel task model which is known as static and predictable task model and could be applied to various embedded or ubiquitous systems. In pinwheel task model, each task's priority is static and its execution sequence could be predetermined. There have been many static approaches to power-aware scheduling in pinwheel task model. But, in this paper, we will show that the dynamic priority scheduling results in power-aware scheduling could be applied to pinwheel task model. This method is more effective than adopting the previous static priority scheduling methods in saving energy consumption and, for the system being still static, it is more tractable and applicable to small sized embedded or ubiquitous computing. Also, we introduce a novel power-aware scheduling algorithm which exploits all slacks under preemptive earliest-deadline first scheduling which is optimal in uniprocessor system. The dynamic priority method presented in this paper could be applied directly to static systems of pinwheel task model. The simulation results show that the proposed algorithm with the algorithmic complexity of O(n) reduces the energy consumption by 10-80% over the existing algorithms. PMID- 25121127 TI - Locked mouths: Tooth loss in a women's prison in northeastern Brazil. AB - BACKGROUND: Prisoners, in general, exhibit unsatisfactory oral conditions, especially with regard to the large number of missing teeth and with untreated caries. The aim of this study was to assess tooth loss, use of and need for prosthetic rehabilitation, and use of dental services among inmates. A cross sectional study involving 65 inmates was developed at the Regional Women's Prison of Campina Grande, Brazil. Data regarding sociodemographic and sentencing profile, use of dental services, dental morbidity, and self-perceived oral health impacts were investigated. Chi-square, Pearson, and Kruskal-Wallis (P < 0.05) statistical tests were used. The mean tooth loss was 11.3 teeth. Significant association between tooth loss and oral health satisfaction (P = 0.049), self perceived need for dental prosthesis (P < 0.001), uncomfortable teeth brushing (P = 0.005), difficult speaking (P = 0.002), and difficulty in performing routine tasks (P = 0.025) was observed. It was observed that 29.2% of inmates were using some type of prosthesis, all deemed unsuitable for use, and 78.5% of inmates needed prosthetic rehabilitation. The oral health condition of the population studied was found to be poor, and prisoners showed significant tooth loss and need for dentures, with the aggravation of having tooth extraction as the major reason for seeking dental care. PMID- 25121128 TI - Train repathing in emergencies based on fuzzy linear programming. AB - Train pathing is a typical problem which is to assign the train trips on the sets of rail segments, such as rail tracks and links. This paper focuses on the train pathing problem, determining the paths of the train trips in emergencies. We analyze the influencing factors of train pathing, such as transferring cost, running cost, and social adverse effect cost. With the overall consideration of the segment and station capability constraints, we build the fuzzy linear programming model to solve the train pathing problem. We design the fuzzy membership function to describe the fuzzy coefficients. Furthermore, the contraction-expansion factors are introduced to contract or expand the value ranges of the fuzzy coefficients, coping with the uncertainty of the value range of the fuzzy coefficients. We propose a method based on triangular fuzzy coefficient and transfer the train pathing (fuzzy linear programming model) to a determinate linear model to solve the fuzzy linear programming problem. An emergency is supposed based on the real data of the Beijing-Shanghai Railway. The model in this paper was solved and the computation results prove the availability of the model and efficiency of the algorithm. PMID- 25121129 TI - A note on parametric surfaces in Minkowski 3-space. AB - With the help of the Frenet frame of a given pseudo null curve, a family of parametric surfaces is expressed as a linear combination of this frame. The necessary and sufficient conditions are examined for that curve to be an isoparametric and asymptotic on the parametric surface. It is shown that there is not any cylindrical and developable ruled surface as a parametric surface. Also, some interesting examples are illustrated about these surfaces. PMID- 25121130 TI - Gender dysphoria: the role of sex reassignment surgery. PMID- 25121132 TI - Reconfigurable ring filter with controllable frequency response. AB - Reconfigurable ring filter based on single-side-access ring topology is presented. Using capacitive tuning elements, the electrical length of the ring can be manipulated to shift the nominal center frequency to a desired position. A synthesis is developed to determine the values of the capacitive elements. To show the advantage of the synthesis, it is applied to the reconfigurable filter design using RF lumped capacitors. The concept is further explored by introducing varactor-diodes to continuously tune the center frequency of the ring filter. For demonstration, two prototypes of reconfigurable ring filters are realized using microstrip technology, simulated, and measured to validate the proposed concept. The reconfigured filter using lumped elements is successfully reconfigured from 2 GHz to 984.4 MHz and miniaturized by 71% compared to the filter directly designed at the same reconfigured frequency, while, for the filter using varactor-diodes, the frequency is chosen from 1.10 GHz to 1.38 GHz spreading over 280 MHz frequency range. Both designs are found to be compact with acceptable insertion loss and high selectivity. PMID- 25121131 TI - Sequence variants of ADIPOQ and association with type 2 diabetes mellitus in Taiwan Chinese Han population. AB - Diabetes is a serious global health problem. Large-scale genome-wide association studies identified loci for type 2 diabetes mellitus (T2DM), including adiponectin (ADIPOQ) gene and transcription factor 7-like 2 (TCF7L2), but few studies clarified the effect of genetic polymorphisms of ADIPOQ and TCF7L2 on risk of T2DM. We attempted to elucidate association between T2DM and polymorphic variations of both in Taiwan's Chinese Han population, with our retrospective case-control study genotyping single nucleotide polymorphisms (SNPs) in ADIPOQ and TCF7L2 genes both in 149 T2DM patients and in 139 healthy controls from Taiwan. Statistical analysis gauged association of these polymorphisms with risk of T2DM to show ADIPOQ rs1501299 polymorphism variations strongly correlated with T2DM risk (P = 0.042), with rs2241766 polymorphism being not associated with T2DM (P = 0.967). However, both polymorphisms rs7903146 and rs12255372 of TCF7L2 were rarely detected in Taiwanese people. This study avers that ADIPOQ rs1501299 polymorphism contributes to risk of T2DM in the Taiwanese population. PMID- 25121134 TI - Damage assessment of two-way bending RC slabs subjected to blast loadings. AB - Terrorist attacks on vulnerable structures and their individual structural members may cause considerable damage and loss of life. However, the research work on response and damage analysis of single structural components, for example, a slab to blast loadings, is limited in the literature and this is necessary for assessing its vulnerability. This study investigates the blast response and damage assessment of a two-way bending reinforced concrete (RC) slab subjected to blast loadings. Numerical modeling and analysis are carried out using the commercial finite element code LS-DYNA 971. A damage assessment criterion for the two-way bending RC slab is defined based on the original and residual uniformly distributed load-carrying capacity. Parametric studies are carried out to investigate the effects of explosive weight and explosive position on the damage mode of the two-way RC slab. Some design parameters, such as the boundary conditions and the negative reinforcement steel bar length, are also discussed. The illustrated results show that the proposed criterion can apply to all failure modes. The damage assessment results are more accurate than the ones due to the conventional deformation criterion. PMID- 25121133 TI - On the open problem related to rank equalities for the sum of finitely many idempotent matrices and its applications. AB - Tian and Styan have shown many rank equalities for the sum of two and three idempotent matrices and pointed out that rank equalities for the sum P1 + ?+P k with P1,..., P k be idempotent (k > 3) are still open. In this paper, by using block Gaussian elimination, we obtained rank equalities for the sum of finitely many idempotent matrices and then solved the open problem mentioned above. Extensions to scalar-potent matrices and some related matrices are also included. PMID- 25121135 TI - Efficient and scalable graph similarity joins in MapReduce. AB - Along with the emergence of massive graph-modeled data, it is of great importance to investigate graph similarity joins due to their wide applications for multiple purposes, including data cleaning, and near duplicate detection. This paper considers graph similarity joins with edit distance constraints, which return pairs of graphs such that their edit distances are no larger than a given threshold. Leveraging the MapReduce programming model, we propose MGSJoin, a scalable algorithm following the filtering-verification framework for efficient graph similarity joins. It relies on counting overlapping graph signatures for filtering out nonpromising candidates. With the potential issue of too many key value pairs in the filtering phase, spectral Bloom filters are introduced to reduce the number of key-value pairs. Furthermore, we integrate the multiway join strategy to boost the verification, where a MapReduce-based method is proposed for GED calculation. The superior efficiency and scalability of the proposed algorithms are demonstrated by extensive experimental results. PMID- 25121136 TI - Stochastic optimized relevance feedback particle swarm optimization for content based image retrieval. AB - One of the major challenges for the CBIR is to bridge the gap between low level features and high level semantics according to the need of the user. To overcome this gap, relevance feedback (RF) coupled with support vector machine (SVM) has been applied successfully. However, when the feedback sample is small, the performance of the SVM based RF is often poor. To improve the performance of RF, this paper has proposed a new technique, namely, PSO-SVM-RF, which combines SVM based RF with particle swarm optimization (PSO). The aims of this proposed technique are to enhance the performance of SVM based RF and also to minimize the user interaction with the system by minimizing the RF number. The PSO-SVM-RF was tested on the coral photo gallery containing 10908 images. The results obtained from the experiments showed that the proposed PSO-SVM-RF achieved 100% accuracy in 8 feedback iterations for top 10 retrievals and 80% accuracy in 6 iterations for 100 top retrievals. This implies that with PSO-SVM-RF technique high accuracy rate is achieved at a small number of iterations. PMID- 25121137 TI - Generalized equilibrium problem with mixed relaxed monotonicity. AB - We extend the concept of relaxed alpha-monotonicity to mixed relaxed alpha-beta monotonicity. The concept of mixed relaxed alpha-beta-monotonicity is more general than many existing concepts of monotonicities. Finally, we apply this concept and well known KKM-theory to obtain the solution of generalized equilibrium problem. PMID- 25121138 TI - Thermal cycling life prediction of Sn-3.0Ag-0.5Cu solder joint using type-I censored data. AB - Because solder joint interconnections are the weaknesses of microelectronic packaging, their reliability has great influence on the reliability of the entire packaging structure. Based on an accelerated life test the reliability assessment and life prediction of lead-free solder joints using Weibull distribution are investigated. The type-I interval censored lifetime data were collected from a thermal cycling test, which was implemented on microelectronic packaging with lead-free ball grid array (BGA) and fine-pitch ball grid array (FBGA) interconnection structures. The number of cycles to failure of lead-free solder joints is predicted by using a modified Engelmaier fatigue life model and a type I censored data processing method. Then, the Pan model is employed to calculate the acceleration factor of this test. A comparison of life predictions between the proposed method and the ones calculated directly by Matlab and Minitab is conducted to demonstrate the practicability and effectiveness of the proposed method. At last, failure analysis and microstructure evolution of lead-free solders are carried out to provide useful guidance for the regular maintenance, replacement of substructure, and subsequent processing of electronic products. PMID- 25121139 TI - Outlier detection method in linear regression based on sum of arithmetic progression. AB - We introduce a new nonparametric outlier detection method for linear series, which requires no missing or removed data imputation. For an arithmetic progression (a series without outliers) with n elements, the ratio (R) of the sum of the minimum and the maximum elements and the sum of all elements is always 2/n : (0,1]. R ? 2/n always implies the existence of outliers. Usually, R < 2/n implies that the minimum is an outlier, and R > 2/n implies that the maximum is an outlier. Based upon this, we derived a new method for identifying significant and nonsignificant outliers, separately. Two different techniques were used to manage missing data and removed outliers: (1) recalculate the terms after (or before) the removed or missing element while maintaining the initial angle in relation to a certain point or (2) transform data into a constant value, which is not affected by missing or removed elements. With a reference element, which was not an outlier, the method detected all outliers from data sets with 6 to 1000 elements containing 50% outliers which deviated by a factor of +/-1.0e - 2 to +/ 1.0e + 2 from the correct value. PMID- 25121140 TI - Uplifting behavior of shallow buried pipe in liquefiable soil by dynamic centrifuge test. AB - Underground pipelines are widely applied in the so-called lifeline engineerings. It shows according to seismic surveys that the damage from soil liquefaction to underground pipelines was the most serious, whose failures were mainly in the form of pipeline uplifting. In the present study, dynamic centrifuge model tests were conducted to study the uplifting behaviors of shallow-buried pipeline subjected to seismic vibration in liquefied sites. The uplifting mechanism was discussed through the responses of the pore water pressure and earth pressure around the pipeline. Additionally, the analysis of force, which the pipeline was subjected to before and during vibration, was introduced and proved to be reasonable by the comparison of the measured and the calculated results. The uplifting behavior of pipe is the combination effects of multiple forces, and is highly dependent on the excess pore pressure. PMID- 25121142 TI - Plasmonic nanoparticle-film calipers for rapid and ultrasensitive dimensional and refractometric detection. AB - In this study, we develop an ultrasensitive nanoparticle (NP)-film caliper that functions with high resolution (angstrom scale) in response to both the dimensions and refractive index of the spacer sandwiched between the NPs and the film. The anisotropy of the plasmonic gap mode in the NP-film caliper can be characterized readily using spectroscopic ellipsometry (SE) without the need for further optical modeling. To the best of our knowledge, this paper is the first to report the use of SE to study the plasmonic gap modes in NP-film calipers and to demonstrate that SE is a robust and convenient method for analyzing NP-film calipers. The high sensitivity of this system originates from the plasmonic gap mode in the NP-film caliper, induced by electromagnetic coupling between the NPs and the film. The refractometric sensitivity of this NP-film caliper reaches up to 314 nm per RIU, which is superior to those of other NP-based sensors. The NP film caliper also provides high dimensional resolution, down to the angstrom scale. In this study, the shift in wavelength in response to the change in gap spacing is approximately 9 nm A(-1). Taking advantage of the ultrasensitivity of this NP-film caliper, we develop a platform for discriminating among thiol containing amino acids. PMID- 25121141 TI - Working capital management, corporate performance, and strategic choices of the wholesale and retail industry in China. AB - We examine the influence of strategic choice on working capital configurations and observe how the relationship between working capital ratio and operational performance differs depending on strategy. By clustering the strategic factors of the wholesale and retail industry, we find three categories of strategies: terminal market strategy, middle market strategy, and hybrid strategy. Using the panel data of the listed companies of the wholesale and retail industry as our sample, we analyze the differences in the ways companies configure working capital, the speed with which working capital adjusts to its target, and the effects of working capital on performance for companies that make different strategic choices. The empirical results suggest that working capital is configured and adjusted to its target in different ways under different competitive strategic choices. This effect is finally transferred to influence the relationship between working capital configuration and operational performance. PMID- 25121143 TI - Choosing to avoid poor-quality healthcare. PMID- 25121144 TI - Delta-9-tetrahydrocannabinol + cannabidiol. A reasonable option for some patients with multiple sclerosis. AB - Conventional drugs have only a limited impact on spasticity associated with multiple sclerosis and are rarely satisfactory. A solution for oral transmucosal delivery (spray) containing a mixture of cannabis extracts (2.7 mg of delta-9 tetrahydrocannabinol + 2.5 mg of cannabidiol per spray) has been granted marketing authorisation in France for patients who are inadequately relieved by standard treatments. Three double-blind, placebo-controlled trials in a total of about 300 patients tested this combination, in addition to ongoing treatment, for periods of 6 to 14 weeks. Individually, none of these trials showed any tangible anti-spastic efficacy, but two combined analyses showed "response rates" of about 35% with the mixture versus about 25% with placebo. In a trial with 572 patients, the 241 patients who "responded" after 4 weeks of treatment were randomised to either continue using the cannabis extract or receive placebo. Twelve weeks later, 75% of patients using the extract were still "responders", versus 51% of patients switched to placebo. The principal adverse effects of the cannabis extracts consist of neuropsychiatric disorders that resolve on treatment withdrawal. The potential for abuse increases with the dose and is tangible from 16 sprays per day. Pharmacokinetic interactions due to P-glycoprotein inhibition are likely. Treatment during pregnancy may lead to neonatal withdrawal symptoms. In practice, about 10% of patients in whom standard anti-spastic medications are unsatisfactory benefit from a specific effect of the cannabis extracts contained in this oral spray. PMID- 25121145 TI - INN common-stem nal. PMID- 25121146 TI - Insulin degludec. Uncertainty over cardiovascular harms. AB - Insulin isophane (NPH) is the standard long-acting human insulin for patients with type 1 and type 2 diabetes. Long-acting human insulin analogues are also available: insulin glargine and insulin detemir. Uncertainties remain concerning their long-term adverse effects. Insulin degludec (Tresiba, Novo Nordisk) is another long-acting human insulin analogue, also approved in the EU for patients with type 1 and type 2 diabetes. It was authorised at a concentration of 100 units per ml, like other insulins, and also at a concentration of 200 units per ml. There are no comparative data on insulin degludec 200 units per ml in patients using high doses of insulin. Insulin degludec has mainly been evaluated in ten randomised, unblinded, "non-inferiority" trials lasting 26 to 52 weeks, nine versus insulin glargine and one versus insulin detemir. Insulin degludec was administered at a fixed time each evening, or in either the morning or evening on alternate days, at varying intervals of 8 to 40 hours between doses. Efficacy in terms of HbA1c control was similar to that of the other insulin analogues administered once a day. The frequency of severe hypoglycaemia was similar in the groups treated with insulin degludec and those treated with the other insulins (10% to 12% among patients with type 1 diabetes and less than 5% in patients with type 2 diabetes). Deaths and other serious adverse events were similarly frequent in the different groups. A meta-analysis of clinical trials, carried out by the US Food and Drug Administration, suggested an increase of about 60% in the incidence of cardiovascular complications, based on a composite endpoint combining myocardial infarction, stroke and cardiovascular death. Other adverse effects observed in these trials were already known to occur with human insulin and its analogues, including weight gain, hypersensitivity reactions, reactions at the injection site, etc. The trials were too short in duration to assess long term harms, particularly cancer. Clinical experience with insulin degludec in pregnant women is very limited. It is therefore best to avoid using this analogue during pregnancy. In France, the concentration of all other insulins injected with a syringe or prefilled pen is 100 units per ml. The new concentration of 200 units per ml contained in insulin degludec prefilled pens creates a risk of confusion and overdose. In practice, there is already a relatively wide range of options available for patients with type 1 or type 2 diabetes who require insulin therapy. As insulin degludec has no proven advantages, it is better to avoid using it, at least pending further data on the risk of cardiovascular events. Insulin isophane remains the first-choice long-acting insulin, while insulin glargine is most appropriate for some patients with type 1 diabetes. PMID- 25121147 TI - Nalmefene. Alcohol dependence: no advance. AB - Alcohol dependence is a chronic, severe and sometimes fatal disease. Psychological and social support is a crucial element of patient management. Acamprosate and naltrexone are the drugs of choice to help patients remain abstinent, but they are only moderately effective. Nalmefene, an opioid receptor antagonist related to naltrexone, has been authorised in the European Union to help alcohol-dependent patients reduce their alcohol consumption. Nalmefene has not been compared with naltrexone or acamprosate in clinical trials. Clinical evaluation is mainly based on two double-blind, randomised, placebo-controlled trials in which nalmefene was taken "on demand" at a dose of one tablet per day. The trials lasted 6 months and included a total of 1322 patients. During an initial two-week period in which all patients received medical and psychosocial support, about one-third of patients in both trials reduced their alcohol consumption without medication. Depending on the subgroup and the trial, about one-third to one-half of patients discontinued medical treatment before the end of the study period. In both trials, patients taking nalmefene had two fewer "heavy drinking days" per month than patients in the placebo groups. However, at the end of the study, they continued to drink heavily at least one week per month on average. Daily alcohol consumption was 5 to 9 grams lower with nalmefene than with placebo. The most frequent adverse effects observed in clinical trials were insomnia, dizziness, headache and nausea, which were severe in more than 10% of patients. Other serious but less frequent adverse effects included confusion, hallucinations and dissociation, usually at the beginning of treatment. These adverse effects affected about 3% of patients treated with nalmefene, a proportion three times higher than in the placebo groups. The consequences of mixing nalmefene with large amounts of alcohol are not known. In practice, the effects of nalmefene in alcohol-dependent patients seeking to cut down or abstain are of questionable clinical relevance. Adverse effects are frequent and less well-determined than those of standard drugs. The impact of nalmefene on the complications of alcohol dependence is not known. The crucial first step in the management of alcohol-dependent patients is to establish a relationship built on trust and to provide psychological and social support. When medication is considered, it is better to choose acamprosate or naltrexone, drugs that are only moderately effective but better-assessed. PMID- 25121148 TI - Medication-induced violence others towards. AB - Violent behaviour towards others is occasionally caused by drug therapy, through sometimes complex and often poorly understood mechanisms. The consequences described in detailed case reports can be serious, including homicide. Many neuropsychotropic drugs can induce violent behaviour: smoking cessation drugs, selective serotonin reuptake inhibitor antidepressants, amphetamines, benzodiazepines and dopamine agonists. Some drugs not used as psychotropic agents have also been implicated, for example: corticosteroids; anti-infective drugs such as mefloquine, efavirenz, atazanavir, ribavirin and alfa interferons; testosterone; and the asthma drug montelukast. The frequency of these adverse effects cannot be reliably assessed using the data available. Only certain reports mention a previous behaviour disorder. In practice, it is helpful to inform patients if the drugs they are taking can provoke violent behaviour. It is advisable to ask these patients about any behavioural changes and to encourage them to inform members of their family or carers, to ensure that these changes are identified and their consequences averted. In addition, remind them that alcohol increases the risk. PMID- 25121149 TI - Problems encountered in the pharmacovigilance of violence and aggression. PMID- 25121150 TI - Alzheimer's disease in France: too many patients exposed to drug interactions involving cholinesterase inhibitors. AB - A study based on data from the French national health insurance system, for the period 2003-2011, has shown that patients with Alzheimer's disease receiving a cholinesterase inhibitor were exposed to another drug that reduces the heart rate in about 44% of cases, a neuroleptic in 33% of cases, and an antimuscarinic for urinary problems in 8% of cases. Drugs for Alzheimer's disease expose patients to dangerous drug-drug interactions. PMID- 25121151 TI - Capecitabine: toxic epidermal necrolysis and Stevens-Johnson syndrome. PMID- 25121152 TI - Mefloquine: persistent vestibular disorders. PMID- 25121153 TI - Contraceptive implants: pregnancies and problems with removal. PMID- 25121154 TI - Antibiotic therapy for acute appendicitis in adults. Fewer immediate complications than with surgery, but more subsequent failures. AB - Appendectomy is the standard treatment for acute appendicitis. Since the 1990s, antibiotic therapy has sometimes been proposed as an alternative to immediate appendectomy. How effective are antibiotics in adults with uncomplicated acute appendicitis, and what is the risk of complications? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. A systematic review with meta-analysis included four randomised trials of antibiotics versus immediate appendectomy, in 900 patients hospitalised with uncomplicated appendicitis. The studies included only patients with few severe symptoms, thus undermining the strength of the results. Antibiotic therapy was usually administered intravenously first, then orally. The antibiotics used were amoxicillin + clavulanic acid, cefotaxime, or a fluoroquinolone. Metronidazole or tinidazole was often added. The total duration of antibiotic treatment was 8 to 15 days. The overall incidence of complications of appendicitis (perforation, peritonitis and surgical wound infections) was 25% in the immediate appendectomy group versus 18% in the antibiotic group. The frequency of perforations and peritonitis did not differ between the groups. All symptoms of appendicitis disappeared, without relapse or rehospitalisation during the first month, in 78% of patients in the antibiotic group. After one year of follow-up, 63% of patients treated with antibiotics were asymptomatic and had no complications or recurrences. In another systematic review of five randomised trials, outcome at one year was optimal in 73% of patients treated with antibiotics alone versus 97% of patients who had immediate appendectomy. In practice, in early 2014, appendectomy remains the first-line treatment for uncomplicated acute appendicitis. In some still poorly characterised patients, the harm-benefit balance of antibiotic therapy is probably better than that of immediate appendectomy. When informed of the risks, some patients are likely to choose antibiotic therapy. PMID- 25121155 TI - Towards better patient care: drugs to avoid in 2014. AB - In order to help healthcare professionals and patients choose high-quality treatments and avoid harms, we have updated our list of drugs to avoid in early 2014. Prescrire's assessments of the harm-benefit balance of new drugs and indications are based on a rigorous procedure that includes a systematic and reproducible literature search, identification of patient-relevant outcomes, prioritisation of the supporting evidence, based on the strength of evidence, comparison with standard treatments; and an analysis of both known and potential adverse effects. Our 2014 review concerns drugs analysed in these pages over a four-year period, from 2010 to 2013. We identified 68 drugs that are potentially more harmful than beneficial in all of their authorised indications. In most cases, other drugs with a better harm-benefit balance are available. In other cases, there is no satisfactory alternative treatment. However, even for serious diseases, this does not justify exposing patients to serious risks when a drug has no proven efficacy. Some drugs can be used within the context of clinical trials, as long as patients enrolled in such studies are informed that the harms and benefits are uncertain and that this is precisely why they are being asked to participate in clinical research. Tailored supportive care is the best option when there are no available treatments capable of improving the prognosis, beyond the placebo effect. PMID- 25121156 TI - The finances of Association Mieux Prescrire: 2013 Prescrire annual report. PMID- 25121157 TI - Anti-D prophylaxis: past, present and future. AB - The new British Committee for Standards in Haematology (BCSH) guidelines for the use of anti-D immunoglobulin in pregnancy provide a welcome clarification of the use of anti-D in ectopic pregnancy and after red cell salvage during caesarean section, of dosing with different preparations and distinguishing non-immune and immune anti-D. The routine use of anti-D prophylaxis (RAADP) to prevent Rhesus (Rh) D alloimmunisation during the third trimester is well established and requires careful and well-audited local implementation to achieve the maximum public health benefit. In the UK, such scrutiny may be provided by the reporting of failed anti-D prophylaxis at women who have produced an immune anti-D that is detectable for the first time in the current pregnancy through the voluntary Serious Hazards of Transfusion reporting scheme (SHOT). Application of fetal RHD genotyping would avoid giving anti-D to RhD negative women carrying an RhD negative fetus. RAADP is directed by fetal RHD genotyping in some countries in Northern Europe led by the Netherlands and Denmark. The economic case for RAADP directed by fetal RHD genotyping needs to be carefully evaluated and in England is under consideration by National Institute for Health and Clinical Excellence (NICE). Possible future developments include the use of monoclonal anti-D preparations, now in advanced clinical trials, and also testing the hypothesis that directed RAADP from early in the second trimester may further reduce anti-D immunisation. PMID- 25121158 TI - BCSH guideline for the use of anti-D immunoglobulin for the prevention of haemolytic disease of the fetus and newborn. PMID- 25121159 TI - Baseline extracellular potassium level as an indicator of the rate of increase of the same on further storage in CPDA-1 whole blood units: a potential approach to complement FIFO system for prioritisation of blood bags for release from blood-banks. AB - BACKGROUND: Potassium levels in stored blood bags increases as they age. Hyperkalemia in transfused blood has undesirable cardiac effects. MATERIALS AND METHODS: Within a 19-month period, baseline and weekly samples from 15 CPDA-1 whole blood bags were collected till 28 days of storage and analysed for potassium, sodium, uric acid, albumin and whole blood haemoglobin. RESULTS: One unit increase in baseline (0 day) potassium in extracellular fluid of blood units was associated with the following increases in potassium levels on later days of storage: around two unit increase at 1 week (r2 = 0.50, P < 0.01) of storage; four units increase at 2 weeks (r2 = 0.64, P < 0.001) and 3 weeks (r2 = 0.51, P < 0.01) of storage; six units at 4 weeks (r2 = 0.53, P < 0.01) of storage. Baseline whole blood haemoglobin showed a moderate association with baseline potassium (r2 = 0.36, P < 0.05) and 2-week potassium (r2 = 0.35, P < 0.05) values. CONCLUSION: For CPDA-1 blood bags (i) low baseline potassium blood bags might be preferred for transfusion in cases demanding a low potassium load and (ii) coordinating the 'first-in-first-out' (FIFO) policy with 'early release of blood-bags with high initial potassium' might be helpful in improving the release of suitable blood units from blood-banks. PMID- 25121160 TI - Transfusion of packed red blood cells reduces selenium levels and increases lipid peroxidation in an in vivo ovine model. AB - BACKGROUND: Oxidative stress from surgery or critically illness has been shown to adversely contribute to morbidity and mortality. Recent studies record that oxidative stress is heightened following packed red blood cell (PRBC) transfusions and that products of oxidative stress accumulate as the PRBC ages. However, there are no studies that investigate if transfusion of aged PRBC actually increases the recipient's oxidative stress profile more than fresh PRBC. OBJECTIVE: To compare the effect of fresh vs aged PRBC transfusions on the recipient's oxidative stress using an ovine model. MATERIALS AND METHODS: Male sheep were transfused with either fresh (n = 6) or aged (n = 6) ovine PRBC, and serial blood samples taken. Plasma samples were analysed for lipid peroxidation using the thiobarbituric acid reactive substances (TBARS) assay. This served as an indicator of oxidative injury. Antioxidant function and trace element levels were also measured. RESULTS: Like human PRBC, the ovine PRBC had negligible selenium levels. Irrespective of age, PRBC transfusion was associated with reduced selenium levels and antioxidant function, which correlated with increased markers of lipid peroxidation. CONCLUSION: Transfusion of selenium poor PRBC can dilute selenium levels and compromise glutathione peroxidase antioxidant activity and thereby allow lipid peroxidation. As there was no evidence that aged PRBC induced more severe oxidative injury this suggests that selenium dilution is a key underlying mechanism. Further studies are needed to assess the impact of transfusion-related oxidative stress in massive transfusions. PMID- 25121161 TI - Job satisfaction, organisation commitment and retention in the public workforce: a survey among pharmacists in Malaysia. AB - OBJECTIVES: The aims of the study were to assess job satisfaction and organisational commitment among pharmacists working in the public sector and its influence on their likelihood to stay within the public workforce. METHODS: A cross-sectional survey was conducted among all fully registered pharmacists (FRPs) in the northern states of Malaysia in 2009 (n = 467). The questionnaire consisted of three sections to capture the demographic characteristics of the respondents, assess job satisfaction and organisational commitment of the respondents and their likelihood of staying in public service. KEY FINDINGS: A total of 247 FRPs (response rate 52.9%) in the northern region of Malaysia participated in this survey. Majority of the respondents were women (n = 205, 83.0%), of Chinese ethnicity (n = 155, 62.8%), graduates from public universities (n = 173, 70.0%), single (n = 172, 69.6%), with a median age of 27 years (interquartile range (IQR) 2.0) and had worked with the Ministry of Health for a median of 2.75 years (IQR 1.63). The mean job satisfaction and organisational commitment score were 58.09 (standard deviation (SD) 11.83) and 53.46 (SD 6.65) respectively out of a maximum possible score of 90. Majority of the respondents claimed that they were likely to stay in public service (n = 176, 71.3%). Their likelihood of staying in public service was affected by respondents' gender, ethnicity, job satisfaction and organisational commitment. CONCLUSIONS: The findings from this study provide stakeholders with evidence on factors and issues affecting pharmacists' job satisfaction and commitment in the public workforce as well as the likely turnover rate with an early cohort of pharmacists affected by the compulsory service. PMID- 25121163 TI - [Impact of tumor morcellation during the surgical extraction of solid tumors]. PMID- 25121164 TI - [CD74-NRG1: a new fusion gene in lung adenocarcinomas characterizing mucinous adenocarcinomas]. PMID- 25121165 TI - What prescribing means to pharmacists: a qualitative exploration of practising pharmacists in Alberta. AB - OBJECTIVE: In 2007 Alberta, Canada, became the first North American jurisdiction to adopt prescribing legislation for pharmacists. In light of these legislative changes and expanded scope of pharmacy practice, we evaluated what 'prescribing' means to pharmacists in Alberta and the application of prescribing in pharmacy practice. METHODS: We invited pharmacists to participate in semi-structured telephone interviews using closed and open-ended questions. Pharmacists working in community, hospital or other settings were selected using a mix of random and purposive sampling. Interviews were audiorecorded and transcribed, and data were entered into nVIVO 9 software. Transcriptions were analysed by two investigators using an interpretive description approach to identify themes. KEY FINDINGS: Thirty-eight pharmacists were interviewed, of whom 13 had additional (independent) prescribing authorization. Prescribing had a wide breadth of meaning to the pharmacists in our study, which included writing a new prescription and extending an existing prescription, as well as advising on non prescription medications. Pharmacists described prescribing in terms of the physical act of writing the prescription and as part of the patient care process as well as the legislated definition of pharmacist prescribing. The sense of increased responsibility associated with prescribing was noted by many pharmacists. CONCLUSION: Prescribing had diverse meanings to pharmacists in our study, and appeared to be context-specific. Understanding the meaning prescribing holds for individual pharmacists is important to explore whether pharmacist's definition of this expanded scope has shaped pharmacists' enactment of prescribing practice. PMID- 25121166 TI - Langerhans cell histiocytosis with atypical histiocytic marrow infiltration. PMID- 25121167 TI - Doublet spherocytes. PMID- 25121168 TI - Objective and subjective socioeconomic status and health symptoms in patients following hematopoietic stem cell transplantation. AB - OBJECTIVE: Recent research indicates that subjective socioeconomic status (SES) - the perception of one's own SES compared with other people - is an important predictor of cancer-related health outcomes. Subjective SES may function as a psychosocial mechanism by which objective SES affects health, well-being, and, more broadly, quality of life among cancer survivors. This study tested whether the association between objective SES and indicators of quality of life was mediated by subjective SES in a sample of cancer survivors who had undergone hematopoietic stem cell transplantation. METHODS: Hematopoietic stem cell transplantation survivors (N=268) completed measures of objective and subjective SES, along with four measures related to quality of life (depressive symptoms, health-related quality of life, symptoms of generalized distress, and posttraumatic stress disorder symptoms). RESULTS: Higher objective SES was associated with greater quality of life across all four measures. Subjective SES mediated the relationship between objective SES and depressive symptoms (total indirect effect b=-0.09, 95% confidence interval [CI] [-0.15, -0.05]), generalized distress (total indirect effect b=-0.08, 95% CI [-0.13, -0.04]), health-related quality of life (total indirect effect b=0.10, 95% CI [0.06, 0.17]), and posttraumatic stress disorder (total indirect effect b=-0.08, 95% CI [-0.14, -0.04]). CONCLUSIONS: Findings extend work on subjective SES to cancer and suggest that SES gradients in patient outcomes after cancer may reflect not only material resources but also psychosocial factors related to rank within social hierarchies. Further research may provide insights useful for reducing disparities in this population PMID- 25121170 TI - New European clinical trials regulation is published. PMID- 25121169 TI - Faecal carriage of Pseudomonas aeruginosa in healthy humans: antimicrobial susceptibility and global genetic lineages. AB - The aim of this study was to analyse the Pseudomonas aeruginosa faecal carriage rate in 98 healthy humans and to perform the phenotypic and genotypic characterization of recovered isolates. The genetic relatedness among the isolates was analysed by pulsed-field gel electrophoresis and multilocus sequence typing that was compared with worldwide epidemic clones. Pseudomonas aeruginosa was isolated from eight healthy individuals (8.2%), and two of them remained colonized after 5 months (in one case by the same clone). All 10 isolates (one/sample) were susceptible to 14 tested antipseudomonal agents and lacked integron structures. Six pulsed-field gel electrophoresis patterns and six sequence types (ST245, ST253, ST254, ST274, ST663 and the new one, ST1059) were identified among them. Four groups of OprD alterations were detected based on mutations and deletions related to PAO1 reference strain in our carbapenem susceptible strains. This is the first study focused on P. aeruginosa from faecal samples of healthy humans that provides additional insights into the antimicrobial resistance and genetic diversity of P. aeruginosa. Although the isolates were antimicrobial susceptible, most of the sequence types detected were genetically related to Spanish epidemic clones or globally spread sequence types, such as ST274 and ST253. PMID- 25121171 TI - 2014 ASCO Annual Meeting. PMID- 25121172 TI - 2014 SNMMI Annual Meeting. PMID- 25121173 TI - Targeting genetic drivers of lung cancer improves survival. PMID- 25121174 TI - Siltuximab in transplant-ineligible patients with myeloma. PMID- 25121175 TI - Patients with polycystic kidney disease at lower risk of cancer. PMID- 25121176 TI - Axitinib: VEGF inhibition in advanced thyroid cancer. PMID- 25121177 TI - Cancer patients missing out on treatment for heart problems. PMID- 25121178 TI - A new combination therapy for premenopausal breast cancer. PMID- 25121179 TI - Ibrutinib monotherapy in chronic lymphoid leukaemia. PMID- 25121180 TI - Enzalutamide in castration-resistant prostate cancer. PMID- 25121181 TI - Federal court judge blocks 340B orphan drug exclusion rule. PMID- 25121182 TI - E-cigarette market expands online. PMID- 25121183 TI - Study estimates economic returns from UK cancer research. PMID- 25121184 TI - Effect of partial pleurectomy on survival in mesothelioma. PMID- 25121185 TI - Exhibition: Cancer Baby: cancer meets Kawaii culture. PMID- 25121187 TI - Emory Guy Simmons 1920-2013. PMID- 25121186 TI - Consensus guidelines for the management of hepatitis C infection. AB - At prevalence of 2.7% in the early 1990's, it is estimated that approximately 500,000 people in Saudi Arabia have been exposed to the hepatitis C virus (HCV). Over 80% of such individuals remain infected and most of them progress to chronic hepatitis C (CHC), cirrhosis, and/or hepatocellular carcinoma (HCC). The incidence of newly acquired hepatitis C infection in Saudi Arabia has declined with the recent reported prevalence of approximately 1%. This decline is largely due to the early implementation of testing of blood donors for HCV. However, it is pertinent that measures are taken to identify patients already infected and offer treatment to those with good prognostic factors. Hepatitis C genotype 4, the most predominant genotype in Saudi Arabia (62%) has been resistant to conventional interferon (IFN) therapy and sustained response rate to combination therapy with IFN plus ribavirin (RBV) has been poor. The recently completed Ministry of Health (MOH) clinical trial reports improved sustained virological response (SVR) rate of 65.2% among week 12 early responders of HCV genotype 4 chronic hepatitis patients using pegylated (PEG)-IFN alfa-2a (40 KD) plus RBV. This encouraging process calls for a change in patient management towards a more community-based approach. With the aim of assessing these changes and defining a management strategy for HCV infected patients in Saudi Arabia, a consensus conference was held and consensus guidelines issued. The final recommendation will be made available to all MOH, tertiary and non-government hospitals in the Kingdom to provide uniform care to all CHC patients. Based on the SVR of the above mentioned clinical trial, the committee recommends treatment for patients with histologically proven CHC, with elevated serum alanine aminotransferase (ALT) and positive HCV ribonucleic acid (RNA). Patients with normal serum ALT may not be treated if liver histology is normal or reveals only minimal changes. Patients with decompensated cirrhosis should not be treated. Hepatitis C virus genotype 4 patients should be treated with combination therapy of PEG IFN alfa-2a (180 MUg/week) plus RBV (1000 - 1200 mg daily according to body weight) for 48 weeks. Patients with HCV non-genotype 4 may also be treated with combination therapy of PEG-IFN plus RBV, but genotypes 2 and 3 patients can be treated for 6 months only. Stringent monitoring for virological biochemical responses is eminent and provides the opportunity to interrupt treatment at week 12 in non responders. A strong counseling program should be available for untreated patients, relapsers and non-responders. An exit program for liver transplantation should also be set up. It is likely that some of the consensus recommendations will have to be revised in the short-term, as the results of ongoing studies become available. Future research in advances in diagnosis, pathogenesis, natural history, management and prevention should be encouraged and newer therapies for CHC patients should be sought for non-responders. PMID- 25121189 TI - A 49 year-old woman with a pineal mass. PMID- 25121188 TI - Climate-change impacts on sandy-beach biota: crossing a line in the sand. AB - Sandy ocean beaches are iconic assets that provide irreplaceable ecosystem services to society. Despite their great socioeconomic importance, beaches as ecosystems are severely under-represented in the literature on climate-change ecology. Here, we redress this imbalance by examining whether beach biota have been observed to respond to recent climate change in ways that are consistent with expectations under climate change. We base our assessments on evidence coming from case studies on beach invertebrates in South America and on sea turtles globally. Surprisingly, we find that observational evidence for climate change responses in beach biota is more convincing for invertebrates than for highly charismatic turtles. This asymmetry is paradoxical given the better theoretical understanding of the mechanisms by which turtles are likely to respond to changes in climate. Regardless of this disparity, knowledge of the unique attributes of beach systems can complement our detection of climate-change impacts on sandy-shore invertebrates to add rigor to studies of climate-change ecology for sandy beaches. To this end, we combine theory from beach ecology and climate-change ecology to put forward a suite of predictive hypotheses regarding climate impacts on beaches and to suggest ways that these can be tested. Addressing these hypotheses could significantly advance both beach and climate change ecology, thereby progressing understanding of how future climate change will impact coastal ecosystems more generally. PMID- 25121190 TI - 74 year-old woman with systemic lupus erythematosis and recent onset ataxia. PMID- 25121191 TI - 72 year old female with leg weakness. PMID- 25121192 TI - A 54 year-old man with progressive vision and hearing loss. PMID- 25121340 TI - Resonance electron attachment to tetracyanoquinodimethane. AB - Resonance interaction of low energy (0-14 eV) electrons with gas-phase 7,7,8,8 tetracyanoquinodimethane (TCNQ) was investigated using dissociative electron attachment (DEA) spectroscopy. Spectral features associated with formation of long-lived TCNQ molecular negative ions are detected at incident electron energies of 0.3, 1.3, and 3.0 eV. A variety of negative fragments is observed around 4 eV, and slow (microseconds) dissociative decay channels are detected at about 3 eV, in competition with simple re-emission of the captured electron. The average electron detachment time from the TCNQ(-) negative ions formed at 3 eV was evaluated to be 250 MUs. The experimental findings are interpreted with the support of density functional theory (DFT) calculations of the empty orbital energies, scaled with an empirical equation, and by comparison with earlier electron transmission spectroscopy (ETS) data. A possible mechanism for the unusual formation of long-lived molecular anions above zero energy (up to 3 eV) is briefly discussed. The present results on the interactions between electrons and isolated TCNQ molecules could give more insight into processes observed in TCNQ adsorbates under conditions of excess negative charge. In particular, electron-stimulated surface reactions are hypothesized, likely occurring when condensed TCNQ molecules are exposed to electron beam irradiation. PMID- 25121341 TI - Optimization of liganded polyethylenimine polyethylene glycol vector for nucleic acid delivery. AB - The delivery of nucleic acids into cells is an attractive approach for cancer therapy. Polyethylenimine (PEI) is among the most efficient nonviral carriers. Recent studies have demonstrated that PEI can be conjugated to targeting ligands, such as epidermal growth factor (EGF) and transferrin (Schaffert et al., 2011; Abourbeh et al., 2012; Ogris et al., 1999). Herein we present a simplified protocol for producing homogeneous preparations of PEGylated linear PEI: LPEI PEG2k. We generated two well-characterized copolymers, with ratios of LPEI to PEG of 1:1 and 1:3. These copolymers were further conjugated through disulfide bonds to a Her-2 targeting moiety, Her-2 affibody. This reaction yielded two triconjugates that target Her-2 overexpressing tumors. Polyplexes were formed by complexing plasmid DNA with the triconjugates. We characterized the biophysical properties of the conjugates, and found that the triconjugate 1:3 polyplex had lower zeta potential, larger particle size, and more heterogeneous shape than the triconjugate 1:1 polyplex. Triconjugate 1:1 and triconjugate 1:3 polyplexes were highly selective toward cells that overexpress Her-2 receptors, but triconjugate 1:1 polyplex was more efficient at gene delivery. Our studies show that the biophysical and biological properties of the conjugates can be profoundly affected by the ratio of LPEI:PEG2k:ligand. The procedure described here can be adapted to generate a variety of triconjugates, simply by changing the targeting moiety. PMID- 25121342 TI - Maternal lipids in pre-eclampsia: innocent bystander or culprit? AB - Pre-eclampsia continues to be a challenge--to understand the underlying pathogenesis and to prevent or treat in the clinical setting. One area of potential therapies opening up is treatment of maternal lipids and clinical trials are underway using statins in early pre-eclampsia. At present, most potential therapies to treat lipids cannot be recommended for general use in pregnancy and if we were to target maternal lipids to reduce rates of pre eclampsia, very large numbers of women may need to be treated. Prior to reaching that point, we first need to understand whether maternal lipids are pathogenic in the processes underlying pre-eclampsia. The aim of this review is to examine the role of lipids in the pathogenesis and outcomes of pre-eclampsia, how abnormal lipid genes may be implicated and consider whether treatment of hyperlipidemia has a more general place in the prevention or treatment of pre-eclampsia. PMID- 25121343 TI - Synthetic methods for compounds having CF3-S units on carbon by trifluoromethylation, trifluoromethylthiolation, triflylation, and related reactions. PMID- 25121344 TI - Proteins immobilization on the surface of modified plant viral particles coated with hydrophobic polycations. AB - Two hydrophobic cations based on poly-N-ethyl-vinylpyridine were used to produce biologically active complexes. The complexes obtained from tobacco mosaic virus (TMV) spherical particles (SPs), hydrophobic polycation, and a model protein were stable and did not aggregate in solution, particularly at high ionic strengths. The nucleic acid-free SPs were generated by thermal remodeling of the TMV (helical rod-shaped plant virus). The model protein preserved its antigenic activity in the ternary complex (SP-polycation-protein). Immobilization of proteins on the surface of SPs coated with hydrophobic cation is a promising approach to designing biologically active complexes used in bionanotechnologies. PMID- 25121346 TI - NMR, calorimetry, and computational studies of aqueous solutions of N-methyl-2 pyrrolidone. AB - N-Methyl-2-pyrrolidone (NMP) is a solvent with applications in different industrial fields. Although largely employed in aqueous mixtures, little is known on the structural and dynamic properties of this system. In order to improve the knowledge on NMP aqueous solutions, useful to the development of their applications, NMR spectroscopy, calorimetric titration, and puckering analysis of molecular dynamics (MD) simulations were employed in this work. Our calorimetric study evidenced the presence of strong interactions between NMP and water and revealed that, under comparable conditions, the solvation of NMP by water results in an interaction stronger than the solvation of water by NMP. Overall, the changes of (1)H and (13)C chemical shifts and 2D ROESY spectra upon dilution suggested a preferential location of water nearby the carbonyl group of NMP and the formation of hydrogen bonding between these two molecules. In parallel, observation of correlation times by (13)C NMR spectroscopy evidenced a different dynamic behavior moving from the NMP-rich region to the water-rich region, characterized by a maximum value at about 0.7 water mole fraction. MD simulations showed that the NMP conformation remains the same over the whole concentration range. Our results were discussed in terms of changes in the NMP assembling upon dilution. PMID- 25121345 TI - Clinical Manifestations and Outcomes of Syphilis-associated Uveitis in Northern Spain. AB - PURPOSE: To describe the clinical characteristics and to assess visual prognosis of patients with syphilis-associated uveitis in northern Spain. METHODS: Retrospective review of clinical records in eight general uveitis referral centers. RESULTS: Since the year 2000, 50 patients have been diagnosed: 31 men and 19 women; median age was 41 (19-76) years. A total of 34% were co-infected with HIV and 24% presented systemic manifestations of syphilis. Median initial visual acuity and vision at last visit in 93 affected eyes was 20/50 (20/20 20/2000) and 20/22 (20/20-20/2000), respectively (p < .0001). The most frequent manifestation was papillitis (33.3%). Fifty percent of eyes with macular edema on admission presented worsening of visual acuity at last visit, whereas frequency of worsening in eyes without edema was 7.1% (p = 0.009). CONCLUSIONS: In our series, patients with syphilitic uveitis were more usually middle-aged men and were frequently co-infected with HIV. Although most patients showed posterior segment involvement, visual prognosis was good. PMID- 25121348 TI - An oxysulfate Fe2O(SO4)2 electrode for sustainable Li-based batteries. AB - High-performing Fe-based electrodes for Li-based batteries are eagerly pursued because of the abundance and environmental benignity of iron, with especially great interest in polyanionic compounds because of their flexibility in tuning the Fe(3+)/Fe(2+) redox potential. We report herein the synthesis and structure of a new Fe-based oxysulfate phase, Fe2O(SO4)2, made at low temperature from abundant elements, which electrochemically reacts with nearly 1.6 Li atoms at an average voltage of 3.0 V versus Li(+)/Li, leading to a sustained reversible capacity of ~125 mAh/g. The Li insertion-deinsertion process, the first ever reported in any oxysulfate, entails complex phase transformations associated with the position of iron within the FeO6 octahedra. This finding opens a new path worth exploring in the quest for new positive electrode materials. PMID- 25121347 TI - Synthesis, characterization, and biological evaluation of new Ru(II) polypyridyl photosensitizers for photodynamic therapy. AB - Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+) (2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine), ptpy = 4'-phenyl 2,2':6',2"-terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and phototoxic index (PI) of 2 (IC50(light): 25.3 MUM, 420 nm, 6.95 J/cm(2); PI >4) and particularly of 1 (IC50(light): 0.62 MUM, 420 nm, 6.95 J/cm(2); PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm(2)) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(-) E. coli (>4 log10 CFU reduction). PMID- 25121349 TI - Comparing apples to oranges: comparative case study of 2 produce carts in Chicago. PMID- 25121350 TI - Information-seeking among chronic disease prevention staff in state health departments: use of academic journals. AB - Use of scientific evidence aids in ensuring that public health interventions have the best possible health and economic return on investment. We describe use of academic journals by state health department chronic disease prevention staff to find public health evidence. We surveyed more than 900 state health department staff from all states and the District of Columbia. Participants identified top journals or barriers to journal use. We used descriptive statistics to examine individual and aggregate state health department responses. On average, 45.7% of staff per state health department use journals. Common barriers to use included lack of time, lack of access, and expense. Strategies for increasing journal use are provided. PMID- 25121351 TI - Hypertension among US adults by disability status and type, National Health and Nutrition Examination Survey, 2001-2010. AB - The prevalence of hypertension among people with disabilities is not well understood. We combined data from the 2001-2010 National Health and Nutrition Examination Survey to obtain estimates of hypertension prevalence by disability status and type (cognitive, hearing, vision, or mobility limitation) and assess the association between disability and hypertension. Overall, 34% of adults with disabilities had hypertension compared with 27% of adults without disabilities; adults with mobility limitations were more likely to have hypertension than adults without disabilities (adjusted prevalence ratio: 1.23; 95% confidence interval: 1.16-1.32). Our results suggest that adults living with disabilities are an important subpopulation to include in hypertension reporting and intervention efforts. PMID- 25121352 TI - Factors related to coronary heart disease risk among men: validation of the Framingham Risk Score. AB - INTRODUCTION: Coronary heart disease (CHD) remains a leading cause of death in the United States. The Framingham Risk Score (FRS) was developed to help clinicians in determining their patients' CHD risk. We hypothesize that the FRS will be significantly predictive of CHD events among men in the Aerobics Center Longitudinal Study (ACLS) population. METHODS: Our study consisted of 34,557 men who attended the Cooper Clinic in Dallas, Texas, for a baseline clinical examination from 1972 through 2002. CHD events included self-reported myocardial infarction or revascularization or death due to CHD. During the 12-year follow-up 587 CHD events occurred. Multivariable-adjusted hazard ratios generated from ACLS analysis were compared with the application of FRS to the Framingham Heart Study (FHS). RESULTS: The ACLS cohort produced similar hazard ratios to the FHS. The adjusted Cox proportional hazard model revealed that men with total cholesterol of 280 mg/dL or greater were 2.21 (95% confidence interval (CI), 1.59-3.09) times more likely to have a CHD event than men with total cholesterol from 160 through 199mg/dL; men with diabetes were 1.63 (95% CI, 1.35-1.98) times more likely to experience a CHD event than men without diabetes. CONCLUSION: The FRS significantly predicts CHD events in the ACLS cohort. To the best of our knowledge, this is the first report of a large, single-center cohort study to validate the FRS by using extensive laboratory and clinical measurements. PMID- 25121353 TI - A new tumour suppression mechanism by p27Kip1: EGFR down-regulation mediated by JNK/c-Jun pathway inhibition. AB - p27Kip1 is a potent inhibitor of cyclin-dependent kinases that drive G1-to-S cell cycle transition. Reduced p27Kip1 expression is prevalent in a wide range of human tumours; however, the exact mechanism(s) of p27Kip1-mediated tumour suppression remains obscure. In the present study, we identified a close inverse relationship between p27Kip1 and EGFR (epidermal growth factor receptor) expression: the parental T24 human bladder cancer cells had high p27Kip1 expression but low EGFR expression and, in striking contrast, the metastatic derivative of T24 (T24T) had low p27Kip1 expression but high EGFR expression. This relationship was also found in various human cancer tissues, and was not only just correlative but also causal; depletion of p27Kip1 in MEF (mouse embryonic fibroblast) cells resulted in markedly elevated EGFR expression, a result reproducible with an Egfr promoter-luciferase reporter in both T24 and MEF cells, suggesting transcriptional repression of EGFR by p27Kip1. Indeed, p27Kip1 was found to regulate EGFR expression via the JNK (c-Jun N-terminal kinase)/c-Jun transcription factor: p27Kip1 deficiency activated JNK/c-Jun, whereas inhibition of JNK/c-Jun by dominant-negative mutants dramatically repressed Egfr transcription. Furthermore, the proximal promoter of the Egfr gene was crucial for its transcription, where the recruiting activity of c-Jun was much greater in p27Kip1-/- cells than in p27Kip1+/+ cells. Introduction of GFP-p27Kip1 into T24T cells suppressed JNK/c-Jun activation, EGFR expression and anchorage-independent growth. The results of the present study demonstrate that p27Kip1 suppresses JNK/c-Jun activation and EGFR expression in MEFs and human bladder cancer cells, and the results obtained are consistent with those from human cancer specimens. The present study provides new insights into p27Kip1 suppression of cancer cell growth, migration and metastasis. PMID- 25121354 TI - Initial staging of Hodgkin's disease: role of contrast-enhanced 18F FDG PET/CT. AB - The objective of this study was to compare the diagnostic accuracy of positron emission tomography/low-dose computed tomography (PET/ldCT) versus the same technique implemented by contrast-enhanced computed tomography (ceCT) in staging Hodgkin's disease (HD).Forty patients (18 men and 22 women, mean age 30 +/- 9.6) with biopsy-proven HD underwent a PET/ldCT study for initial staging including an unenhanced low-dose computed tomography for attenuation correction with positron emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT scan, in the same exam session. A detailed datasheet was generated for illness locations for separate imaging modality comparison and then merged in order to compare the separate imaging method results (PET/ldCT and ceCT) versus merged results positron emission tomography/contrast-enhanced computed tomography (PET/ceCT). The nodal and extranodal lesions detected by each technique were then compared with follow-up data that served as the reference standard.No significant differences were found at staging between PET/ldCT and PET/ceCT in our series. One hundred and eighty four stations of nodal involvement have been found with no differences in both modalities. Extranodal involvement was identified in 26 sites by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences concerning the stage (Ann Arbor).Our study shows a good concordance and conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the initial staging of HD, suggesting that PET/ldCT could suffice in most of these patients. PMID- 25121356 TI - Increased risk of end-stage renal disease in patients with renal cell carcinoma: a 12-year nationwide follow-up study. AB - The effect of renal cell carcinoma (RCC) on the risk for end-stage renal disease (ESRD) has not been confirmed. The present population-based study used the claims data from the Taiwan National Health Institutes from 1998 to 2010 to compare the risk for ESRD in patients with and without RCC.The study cohort consisted of 2940 patients who had newly diagnosed with RCC but no history of ESRD; the control cohort consisted of 23,520 matched patients without RCC. Cox proportional hazard regressions were performed to compute ESRD risk after adjusting for possible confounding factors. Kaplan-Meier analysis and the log-rank test were also used to compare patients and controls.A total of 119 patients in the RCC group (incidence rate: 119/2940; 4.05%) and 160 patients in the control group (incidence rate: 160/23,520; 0.68%) were diagnosed with ESRD during the follow-up period. After adjusting for potential confounders, the RCC group had an ESRD hazard ratio (HR) of 5.63 [95% confidence interval (CI): 4.37-7.24] relative to the control group. In addition, among patients with RCC, females (adjusted HR: 6.95, 95% CI: 4.82-10.1) had a higher risk for ESRD than males (adjusted HR: 4.79, 95% CI: 3.37-6.82). Finally, there were significant joint effects of chronic kidney disease and diabetes on increasing the risk of ESRD in patients with and without RCC (P < 0.01). The limitations of this study include the retrospective design and the inability to assess methods of treatment and measure the aggressiveness of RCC.Our data indicates that RCC is an independent risk factor for ESRD, especially in females. PMID- 25121359 TI - Selective response inversion to NO2 and acetic acid in ZnO and CdS nanocomposite gas sensor. AB - High sensitivity zinc oxide (ZnO) tetrapods (TPs) have been functionalized by nucleating cadmium sulphide (CdS) nanoparticles (NPs) directly on their surface with a spotted coverage thanks to an optimized synthesis in dimethylformamide (DMF). The obtained hybrid coupled material has been used to realize a gas sensing device with a highly porous nanostructured network, in which the proper alternation of ZnO-TPs and CdS-NPs gives rise to unconventional chemoresistive behaviours. Among the different tested gases and vapours, the sensor showed a unique fingerprint response-inversion between 300 degrees C and 400 degrees C only for nitrogen dioxide (NO2) and acetic acid (CH3COOH). PMID- 25121357 TI - High delta-like ligand 4 (DLL4) is correlated with peritumoral brain edema and predicts poor prognosis in primary glioblastoma. AB - Delta-like ligand 4 (DLL4), 1 of the 5 known Notch ligands, is involved in a variety of tumor initiation and progression, particularly in the process of tumor angiogenesis. However, the clinical and prognostic significance of DLL4 in glioblastoma have not been fully elucidated.Tumor tissues from 69 glioblastoma patients were analyzed using immunohistochemistry for DLL4 expression. Peritumoral brain edema (PTBE) on preoperative magnetic resonance imaging of these patients and the relationship with DLL4 expression were evaluated. The effect on prognosis was assessed by using the Kaplan-Meier survival and the Cox proportional hazard model.The results showed that elevated DLL4 expression was primarily distributed in the cytoplasm of tumor vascular endothelial cells and rarely detected in tumor cells. Univariate analysis indicated significant correlation of high DLL4 expression with shorter time to progression (TTP) (P < 0.001) and overall survival (OS) (P < 0.001) in glioblastoma. Multivariate analysis confirmed high DLL4 expression as an unfavorable prognostic indicator for TTP (P < 0.001) and OS (P < 0.001), independent of age, gender, symptom duration, resection degree, and PTBE. Importantly, the study also found that DLL4 expression was positively related with PTBE (Spearman's test: r = 0.845, P < 0.001). A multiple linear regression model was constructed to confirm that the positive index of DLL4 was associated with an increase in maximum extent of PTBE (P < 0.001).It is thus concluded that DLL4 is correlated with PTBE and may be useful for predicting prognosis in glioblastoma. PMID- 25121358 TI - Membranous nephropathy with crescents in a patient with Hashimoto's thyroiditis: a case report. AB - Membranous nephropathy is a common cause of nephrotic syndrome in adults. It usually occurs secondary to underlying disease processes such as autoimmune disorders, malignancy, infection, and drugs. The presentation of nephrotic syndrome with concomitant precipitous decline in renal function warrants investigation of a coexistent disorder.We report the case of a 30-year-old male who presented with symptoms and signs of hypothyroidism.A diagnosis of Hashimoto's thyroiditis was contemplated based on the presence of high serum levels of antithyroglobulin and antithyroid peroxidase antibodies. Upon initiation of treatment with levothyroxine, patient symptomatology improved; however, the laboratory studies demonstrated continued elevated creatinine, hematuria, and proteinuria, which had not been addressed. Two months following treatment initiation, he had progressive deterioration in renal function and proteinuria. A renal biopsy revealed coexistent necrotizing and crescentic glomerulonephritis and membranous nephropathy.The final diagnosis was necrotizing, crescentic glomerulonephritis with superimposed membranous nephropathy likely secondary to Hashimoto's thyrodiitis.Induction treatment with oral cyclophosphamide and prednisone was started.At the end of 6 months of treatment, there was improvement in renal function and proteinuria and maintenance treatment with azathioprine and low-dose prednisone was initiated. This case highlights the importance of precise and detailed evaluation of patients with autoimmune diseases such as Hashimoto's thyroiditis particularly in the presence of active urine sediment. Proper evaluation and diagnosis of such patients has implications on the prognosis and response to treatment. PMID- 25121355 TI - Characteristics of fecal and mucosa-associated microbiota in Chinese patients with inflammatory bowel disease. AB - The intestinal microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD), and geographical and genetic backgrounds impact the composition of the intestinal microbiota. However, there is a lack of evidence regarding the overall changes and characteristics of fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) in Chinese patients with IBD. We recruited 26 patients with Crohn's disease (CD), 46 patients with ulcerative colitis (UC), and 21 healthy individuals; we collected matched fresh fecal and mucosal samples from the same subjects. The microbial communities were studied by 454-pyrosequencing. Community-wide changes in FAM and MAM were observed in patients with IBD. The proportion of several butyrate-producing bacteria, such as of the genera Roseburia, Coprococcus, and Ruminococcus were significantly reduced, whereas the pathogens Escherichia-Shigella and Enterococcus were prevalent in patients with IBD. FAM and MAM were similar between CD and UC. FAM differed from MAM in healthy individuals and patients with UC. In conclusion, the compositions of FAM and MAM were altered in patients with IBD. The reduction of butyrate-producing bacteria and the increase in opportunistic pathogens might be associated with the pathogenesis of IBD. PMID- 25121360 TI - Anaphylactic cardiac collapse, sudden death and the Kounis syndrome. PMID- 25121361 TI - A pilot study on expression of toll like receptors (TLRs) in response to herpes simplex virus (HSV) infection in acute retinal pigment epithelial cells (ARPE) cells. AB - INTRODUCTION: Toll like receptors (TLRs) have been proven to play an important role in mounting the innate immune response in an infected host. The expression of TLRs against herpes simplex virus (HSV) have not been studied in retinitis. Therefore, the current study was undertaken to determine the same using the retinal pigment epithelial (ARPE-19) cell line. MATERIALS AND METHODS: APRE cells cultured in vitro were challenged with HSV 1 and 2 standard strains and 20 other clinical isolates. The cells were observed for cytopathic changes. The cell culture harvest was subjected to RNA extraction using a Total RNA mini kit. The RNA was subjected to reverse transcriptase polymerase chain reaction (PCR) for the amplification of TLRs 3, 4 and 9 and GAPDH housekeeping gene. The amplified products were subjected to electrophoresis on a 2% agarose gel and viewed under a transilluminator. RESULTS: TLR 3 and 4 were expressed by ARPE treated with all the 22 isolates. TLR 9 expression was seen in 16 of the 22 isolates. Bacterial contamination was ruled out by subjecting the harvests to PCR amplification of 16sRNA gene amplification of the eubacterial genome. CONCLUSIONS: The expression of TLR 4 has been reported for the first time in HSV infection. TLR 4 along with TLR 3 and 9 is responsible for the antiviral response in HSV infections. PMID- 25121362 TI - Outcome of surgically treated octogenarians with breast cancer. AB - CONTEXT: Breast cancer is the commonest cancer in women worldwide and its incidence increases with increasing age. In an era of evidence-based practice, there is a paucity of evidence relating to the management of breast cancer in an oncogeriatric population. The authors define oncogeriatrics as cancer in patients aged 80 years or more. AIM: The study aimed to evaluate the survival benefit of surgically managed octogenarians with breast cancer. MATERIALS AND METHODS: This was a retrospective study of octogenarians diagnosed with breast cancer over a 5 year period and who were treated surgically. Kaplan-Meier survival analysis was used to determine the overall survival. The differences in survival were tested using the logrank (Mantel-Cox) test. A P-value of <0.05 was considered to be statistically significant. RESULTS: One hundred patients were included (median age- 84 years, median follow up 3.3 years). A validated adult comorbidity evaluation-27 (ACE-27) index score system was used to characterize patient comorbidities. Fourteen percent of patients had severe comorbidities, 55% nonsevere, 11% no comorbidities, and 20% with unknown comorbidities. The estrogen receptor was positive in 67% of tumors. Eighty-four percent had mastectomy and 15% had wide local excision. Sixty-eight percent had axillary lymph node dissection, 10% had sentinel lymph node biopsy, and 5% had no axillary surgery. The majority (72%) of the tumors were pathologically T1 or T2 tumor. The Nottingham Prognostic Index (NPI) mean score was 4.4. The Kaplan-Meier survival analysis showed a median survival of 5 years. Forty-eight percent died during the observation period, with 54.2% of this group dying of causes unrelated to breast cancer. CONCLUSION: The surgically treated octogenarians in our sample had an acceptable survival outcome. PMID- 25121363 TI - Outcomes of surgical site infections in orthopedic trauma surgeries in a tertiary care centre in India. AB - BACKGROUND: Surgical site infections (SSIs) still cause significant morbidity and mortality despite advances in trauma care. We have studied in this paper the rate of SSIs, their outcomes in patients undergoing interventions for trauma and SSI trends in developing countries. MATERIALS AND METHODS: A 16-month study (May, 2011- August, 2012) was carried out. Patients undergoing interventions for orthopedic trauma were followed and assessed for SSIs and their outcomes and antimicrobial sensitivity patterns of the micro-organisms isolated were noted and correlated. RESULTS: A total of 40 (4.4%) confirmed cases of SSIs were identified among 852 patients of orthopedic trauma. Based on the new CDC criteria, after ruling out cellulitis, only 24 (2.6%) were found to have SSIs. A total of 12.5% of the SSIs were detected during follow-up. Acinetobacter baumannii was the predominant organism as also Staphylococcus aureus. Outcomes observed included changes in antibiotic regime, revision surgery, readmission to hospital and deaths. CONCLUSION: SSI is prevalent in orthopaedic trauma patients and an active surveillance program will help in early management and prevention. PMID- 25121364 TI - Lower levels of serum high-density lipoprotein cholesterol are associated with a worse Duke treadmill score in men but not in women. AB - BACKGROUND: High-density lipoprotein cholesterol (HDL-C) levels are inversely related to the atherosclerotic burden and are higher in women than in men. We aimed to investigate the sex-specific relationship between serum HDL-C levels and the Duke treadmill score (DTS) in this study. MATERIALS AND METHODS: A total of 111 patients (59 men, 42 women) with suspected coronary artery disease (CAD) who underwent exercise treadmill test (EST) were included. Fasting blood samples were obtained for the assessment of serum lipid levels. DTS was calculated for each patient based on EST findings including ST segment deviation and symptoms. RESULTS: Patients were categorized into a moderate to high risk group based on the DTS score (group-I: 38 patients) and a low risk group (group-II: 63 patients). There was a significant positive correlation between serum HDL-C levels and DTS (r = 0.230; P=0.021). The mean HDL-C level was significantly higher in group-II relative to group-I (49.25 +/-11.21 vs. 44.43 +/- 11.18, respectively, P = 0.04). An HDL-C level less than the cut-off value of 41.39 mg/dL predicted a moderate to severe risk DTS with 65% sensitivity and 69% specificity in men (area under curve = 0.732, P = 0.004), but not in women (area under curve = 0.505, P = 0.958). After adjustment for traditional CAD risk factors (age, sex, and smoking status), the relationship of DTS to HDL-C remained significant. (P = 0.030; adjusted OR = 0.948 [95% CI, 0.904-0.995]). CONCLUSION: Low HDL-C levels may be associated with a moderate to high risk Duke treadmill score in men, but not in women. Further research is required to clarify the sex specific relationship between HDL-C and DTS. PMID- 25121365 TI - Association of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and activity of P glycoprotein with response to anti-epileptic drugs. AB - BACKGROUND AND OBJECTIVE: Epilepsy, the most common neurological disorder, has treatment failure rate of 20 to 25%. Inter-individual variability in drug response can be attributed to genetic polymorphism in genes encoding different drug metabolizing enzymes, drug transporters (P-gp), and enzymes involved in sodium channel biosynthesis. The present study attempted to evaluate association of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and P-gp activity with treatment response in patients with epilepsy. MATERIALS AND METHODS: Patients with epilepsy on phenytoin and/or phenobarbital and/or carbamazepine were categorized into responders and non-responders as per the International League Against Epilepsy. Plasma drug concentration was estimated by high-performance liquid chromatography. P-gp activity was measured by flow cytometry using rhodamine efflux. The polymerase chain reaction (PCR-RFLP) was used to study polymorphisms of ABCB1 (C3435T), CYP2C9 (416 C > T, and 1061 A > T), and CYP2C19 (681 G > A and 636 G > A). RESULTS: Of total 117 patients enrolled in this study, genotype data was available for 115 patients. P-gp activity was higher in non-responders (n = 68) compared to responders (n = 47) (P<0.001). No association of 416 C > T and 1061 A > T in CYP2C9 or 681 G > A and 636 G > A in CYP2C19 was observed with response phenotype in genotypic analysis. Significant genotypic (odds ratio, OR = 4.5; 95% CI, 1.04 to 20.99) and allelic association (OR = 1.73; 95% CI, 1.02 to 2.95) was observed with ABCB1 C3435T and response phenotype. CONCLUSIONS: The response to antiepileptics seems to be modulated by C3435T in ABCB1 or P-gp activity. At present, role of other genetic factors in treatment responsiveness in epilepsy appears limited, warranting analysis in a larger cohort. PMID- 25121367 TI - Influence of alcohol on condom use pattern during non-spousal sexual encounter in male migrant workers in north India. AB - CONTEXT: Migrant workers constitute an important risk group for Human Immunodeficiency Virus/Acquired Immuno-Deficiency Syndrome transmission in India. Alcohol consumption before sexual intercourse has been postulated to influence condom use practices. This study aimed to assess this association with regard to non-spousal sexual encounters among male migrant workers in northern India. MATERIALS AND METHODS: A cross-sectional facility-based survey was conducted in 2011. Male migrant workers aged >=18 years, who were born outside Haryana, who had moved to the current location after 15 years of age,had worked in the current factory for at least 1 year, who were willing to participate and were able to give written, informed consent were included in the study. A consecutive sampling was performed. Descriptive, bivariate and multiple logistic regression analyses were carried out. RESULTS: A total of 162 participants reported having experienced non-spousal sexual encounters in the last 1 year. The proportion of men who reported not having used a condom at their last non-spousal sexual encounter was 59.3%, and 78.4% of the men reported having consumed alcohol in the last 1 year. About 48.1% of men reported having consumed alcohol before their last non-spousal sexual encounter. Men who consumed alcohol were three times more likely to not use a condom at their last non-spousal sexual encounter (OR = 3.1, 95% CI: 1.5-6.4). This association persisted even after adjusting for relevant confounders. CONCLUSION: Alcohol consumption had a negative influence on condom use during non-spousal sexual encounter among male migrant workers. An integrated approach to promote condom use and reduce alcohol consumption among migrant men needs to be undertaken through targeted intervention strategies. PMID- 25121366 TI - A prospective study of prevalence and association of peripheral neuropathy in Indian patients with newly diagnosed type 2 diabetes mellitus. AB - BACKGROUND: Diabetic peripheral neuropathy (DPN) predisposes to foot ulceration and gangrene. It has been reported that DPN is lower in Indians relative to Caucasians. Studies among recent onset patients with type 2 diabetes mellitus (T2DM) are very few. We studied the prevalence and risk factors of DPN in patients with newly diagnosed T2DM. MATERIALS AND METHODS: We prospectively studied 195 consecutive patients over age 30 with a duration of diabetes <=6 months. All underwent a clinical and biochemical evaluation and were screened for DPN using Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) as well as the vibration perception threshold using a biothesiometer. We compared the prevalence of peripheral neuropathy (PN) in 75 age- and sex-matched healthy controls. RESULTS: The cases had a mean age of 47.6 +/- 10.2 years (59% males) and duration of symptoms of 5.9 +/- 8.2 months prior to presentation. The overall prevalence of DPN was 29.2% [95% CI 22.8-35.7]. PN among matched control was 10.7% (95% CI 3.5-17.8). The prevalence of DPN showed an increasing trend with age (trend chi-square 11.8, P = 0.001). Abnormal vibration perception threshold was present in 43.3% (95% CI 36.3-50.3) of cases and had a significant correlation with NDS (P = 0.000). Abnormal monofilament testing was present in 6.1% of cases (95% CI 2.7- 9.5). A logistic regression analysis showed that DPN was independently associated with age (P = 0.002) and duration of diabetes prior to presentation (P = 0.02) but not with body mass index, plasma glucose, or HbA1c. CONCLUSIONS: Our study showed high prevalence of PN in recently diagnosed patients with T2DM, which was independently associated with age and duration of symptoms of diabetes prior to the diagnosis. Screening for DPN at diagnosis of diabetes is warranted, especially among older subjects. PMID- 25121369 TI - Brachial plexus injury in live related donor hepatectomy: a chart review. AB - Retrieval of the partial liver graft is a complicated and time-consuming procedure and reported to be associated with brachial plexus injury. We present a case series of brachial plexus injury in live related donor hepatectomy of 95 donors analyzed retrospectively. Seven donors suffered from brachial plexus injuries of varying severity and duration. Out of these, one donor had residual paresis. The reasons could be application of retractors, which may have led to traction and compression above the nerve roots. PMID- 25121368 TI - Prevalence of gastro-esophageal reflux disease in patients with difficult to control asthma and effect of proton pump inhibitor therapy on asthma symptoms, reflux symptoms, pulmonary function and requirement for asthma medications. AB - BACKGROUND: The hypothesis that GER can trigger or exacerbate asthma is supported by several clinical trials that have shown amelioration in asthma symptoms and/or an improvement in pulmonary function after antireflux therapy. AIMS: To investigate the prevalence of GER in patients with difficult to control asthma and to determine the effect of omeprazole on asthma symptoms, reflux symptoms, pulmonary function and on the requirement of asthma medications. MATERIALS AND METHODS: Patients with difficult to control asthma were recruited into the study. All patients underwent esophageal manometry and 24 hour esophageal pH monitoring. Pulmonary function tests were done before and after treatment. The severity of asthma and reflux was assessed by a 1 week pulmonary symptom score(PSS) and reflux symptom score(RSS) respectively before and after treatment. Those who had an abnormal pH study (pH <4 in the distal esophagus for >5% of the time) underwent anti-GER treatment with lifestyle changes, and a proton pump inhibitor (omeprazole 40 mg, bid) for 3 months. Asthma medications were added or deleted based on severity of asthma. RESULTS: Out of 250 asthmatic patients screened, forty patients fulfilled the inclusion criteria. Twenty eight of 40 patients(70%) were diagnosed to have GERD. Of the patients 28 with GER, 8 patients(28.5%) had no reflux symptoms. On 24 hr pH metry, the percentage time pH <4.0 was 10.81 +/- 4.72 and 1.11 +/- 1.21; Deemester score was 37.65 +/- 14.54 and 4.89 +/- 6.39 (p value is 0.0001) in GERD and non-GERD patients respectively.In GERD group, post treatment reflux symptom score(RSS) improved from 22.39 +/- 14.99 to 1.04 +/- 1.07, pulmonary symptom score(PSS) improved from 27.14 +/- 7.49 to 13.82 +/- 4.21 and night time asthma symptom score(NASS) improved from 6.71 +/- 1.80 to 3.04 +/- 1.23 (p-value <0.0001). After treatment, FEV1 and PEFR increased from 1.38 +/- 0.57 and 4.14 +/- 1.97 to 1.47 +/- 0.54 and 5.56 +/- 1.72, respectively (p-value 0.00114). CONCLUSIONS: PPI therapy improves nocturnal asthma symptoms, daytime asthma symptoms, pulmonary function and decreases requirement of asthma medications in these patients. PMID- 25121370 TI - Giambattista Canano and his myology. AB - Giambattista Canano was a sixteenth century Italian anatomist and physician. He was educated at the University of Ferrara where, upon graduation, he was appointed professor of anatomy. While at the university, Canano carried out a pioneering study of skeletal muscles. This study was to be published in a multi volumed book entitled Musculorum Humani Corporis Picturata Dissectio. However, only the section on the muscles of the upper limb was published, as Canano stopped the printing of his book. It is hypothesized that he met Vesalius at the time and saw the proofs of his Fabrica which he assessed as far superior and, consequently, decided to abort his project. The preserved copies of the Dissectio, however, show that the standards of Canano's work surpassed most of the anatomical studies published up to that time. Canano subsequently left the academic position and made a notable career as a physician. His appointments included prestigious positions of physician to the Pope and protomedicus of the House of Este in Ferrara. PMID- 25121371 TI - Pioglitazone: Hype and hope. PMID- 25121372 TI - Hoover's sign: Clinical relevance in Neurology. AB - Hoover's sign was described by Dr. Charles Franklin Hoover more than 100 years back to differentiate between the organic and functional weakness of pyramidal origin. This test is usually performed in the lower limbs and is valuable when on bedside one is not sure about the nature of hemiparesis. A subject with hemiparesis of organic cause while asked to flex the hip of normal leg against resistance will not exert pressure on the hand of examiner placed under the heel on the affected side while in hysterical weakness heightened pressure will be felt on the examiner's hand. The presumed genesis of this sign could be the crossed extensor reflex or the principle of synergistic contraction. It is a useful clinical test in differentiating functional and organic paresis with moderate sensitivity (63%) and high specificity (100%), but there are some limitations which should be kept in mind while evaluating a patient. PMID- 25121373 TI - Bedaquiline: a novel antitubercular drug for multidrug-resistant tuberculosis. AB - Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are emerging global health threats. Bedaquiline is a new antituberculous drug belonging to the diarylquinoline class that efficiently inhibits the adenosine triphosphate synthase enzyme of Mycobacterium tuberculosis. It is a bactericidal and long acting drug. It inhibits both dormant as well as replicating bacterial sub populations and thus shortens the duration of TB treatment. This drug has been approved by the Food and Drug Administration in December 2012 for the management of multidrug resistant-TB. The drug marks the introduction of a new addition to the TB armamentarium after four decades. PMID- 25121374 TI - Telomeres and telomerase: understanding basic structure and potential new therapeutic strategies targeting it in the treatment of cancer. AB - The impact of cancer on humanity is huge and a great deal of research is going on worldwide to find novel therapeutic targets. Telomerase is one such exciting target. Increased telomerase activity provides cancer cells with unlimited proliferative potential and is one of the hallmarks of cancer. This article provides a basic understanding of telomere and telomerase in cancer and summarizes various potential therapeutic approaches used for strategic targeting of telomerase enzyme. Medline, Medscape, EMBASE, Cochrane database, Scopus and clinicaltrials.gov were searched using terms like "telomeres", "telomerase" and "targeted cancer therapy". Journal articles published from 2005 to 2013 describing telomerase-based cancer therapy were screened. PMID- 25121375 TI - Arthritis, a complex connective and synovial joint destructive autoimmune disease: animal models of arthritis with varied etiopathology and their significance. AB - Animal models play a vital role in simplifying the complexity of pathogenesis and understanding the indefinable processes and diverse mechanisms involved in the progression of disease, and in providing new knowledge that may facilitate the drug development program. Selection of the animal models has to be carefully done, so that there is morphologic similarity to human arthritic conditions that may predict as well as augment the effective screening of novel antiarthritic agents. The review describes exclusively animal models of rheumatoid arthritis (RA) and osteoarthritis (OA). The development of RA has been vividly described using a wide variety of animal models with diverse insults (viz. collagen, Freund's adjuvant, proteoglycan, pristane, avridine, formaldehyde, etc.) that are able to simulate/trigger the cellular, biochemical, immunological, and histologic alterations, which perhaps mimic, to a great extent, the pathologic conditions of human RA. Similarly, numerous methods of inducing animal models with OA have also been described (such as spontaneous, surgical, chemical, and physical methods including genetically manipulated animals) which may give an insight into the events of alteration in connective tissues and their metabolism (synovial membrane/tissues along with cartilage) and bone erosion. The development of such arthritic animal models may throw light for better understanding of the etiopathogenic mechanisms of human arthritis and give new impetus for the drug development program on arthritis, a crippling disease. PMID- 25121376 TI - Age appropriate screening for cancer: evidence-based practice in the United States of America. AB - Cancer screening is a well established and integral part of routine care in the Western world including United States. Men and women are recommended to get age specific screening for common cancers like breast, cervical, prostate, and colon. The goal of screening is primary and secondary prevention. Cancer prevention and early detection of cancers has been shown to improve survival rates and decrease mortality by prompt appropriate treatment. This article serves to outline the current guidelines in the United States for cancer screening and the evidence for them as well as discusses the possibility of a similar model of care in India as well as barriers to such a screening program for cancer. The evidence was mostly obtained from systematic reviews done by the United States Preventive Services Task Force guidelines and other peer institutions like American Cancer Society and Agency for Healthcare Research and Quality. PMID- 25121377 TI - Laron syndrome. PMID- 25121378 TI - Needle in a haystack: Intraoperative breakage of pediatric minimal access surgery instruments. AB - The search for tiny bits of broken pediatric minimal access surgery (MAS) instruments in an operative field is akin to the search for a needle in a haystack. With the extension of MAS to the pediatric age group, instruments are becoming smaller and equitably more prone to breakage. When breakages occur, retrieval, especially in the pediatric abdominal cavity, can be challenging. Inability to do so would affect patient safety and also lead to a web of medico legal and ethical issues. We present two cases of intraoperative breakage: An eyeless 3-0 polyamide suture needle and a 2-mm grasper blade both of which were successfully retrieved and fortuitously escaped becoming retained surgical items. PMID- 25121379 TI - Dengue infection presenting as acute hypokalemic quadriparesis. AB - Dengue infection is one of the most common viral hemorrhagic fevers seen in the tropical countries, including India. Its presentation varies from an acute self resolving febrile illness to life-threatening hemorrhagic shock and multiorgan dysfunction leading to death. Neurological presentations are uncommon and limited to case reports only. Most common neurological manifestations being encephalitis, acute inflammatory demyelinating polyradiculoneuropathy, transverse myelitis, and acute disseminated encephalomyelitis.Hypokalemic quadriparesis as a presenting feature of dengue is extremely rare. Here, we report this case of a 33-year-old female, who presented with hypokalemic quadriparesis and was subsequently diagnosed as dengue infection. PMID- 25121380 TI - Hyperparathyroidism complicating pregnancy: a diagnostic challenge? AB - Primary hyperparathyroidism (PHPT) is a rare etiology of hypercalcemia-induced pancreatitis, contributing about 0.4% to 1.5% of cases in the general population and up to 13% of cases during pregnancy. PHPT that occurs during pregnancy is a challenging diagnosis as the physiological changes in calcium homeostasis mask the symptoms of hypercalcemia. PHPT during pregnancy often remains undiagnosed and untreated, and may result in serious clinical implications for the mother and fetus. Most clinicians consider surgery within the second trimester of pregnancy as the treatment of choice in this group of patients. This article refers to a case of a 24-year married woman in whom PHPT was diagnosed for the first time in postpartum period. She succumbed to complications on Day 20 postpartum. Pathological findings revealed metastatic calcification in lungs, pancreas and uterine vessels, chronic pancreatitis and renal cortical necrosis. PMID- 25121381 TI - Chanarin-Dorfman syndrome: clinical report and novel mutation in ABHD5 gene. AB - Chanarin-Dorfman syndrome (CDS) is a multisystem, autosomal recessive genetic disorder characterized by congenital non-bullous ichthyosiform erythroderma with accumulation of lipid droplets in granulocytes and basal keratinocytes. An 18 month-old female child presented with typical dermatological features of CDS. She was born as a collodion baby. Liver biopsy showed micronodular cirrhosis along with macrovesicular hepatic steatosis. Sequencing of all exons and exon-intron boundaries of the ABHD5 gene showed that the patient was homozygous for a novel mutation g.24947delG (c.773 + 1delG) in intron 5. This is the first Indian child with mutation proven CDS. PMID- 25121382 TI - Subcutaneous panniculitis like T cell lymphoma associated with erythromelalgia. AB - Erythromelalgia is a rare disorder that simulates a small fiber neuropathy and patients often have painful erythematous extremities during episodes. It is of two types: A primary or inherited form that is sometimes associated with a Na channel mutation or a secondary disorder associated with an underlying systemic disorder. We present a 19-year-old boy who presented to us with erythromelalgia and a febrile illness with systemic rash. Detailed work-up revealed another unusual condition: Subcutaneous panniculitis like T cell lymphoma (SPTCL). This is the first report of an association of erythromelalgia with SPTCL. PMID- 25121383 TI - Hyperkalemia induced pseudo-myocardial infarction in septic shock. AB - Hyperkalemia is an acute life-threatening disorder presenting to the emergency department. Patients with hyperkalemia may manifest characteristic electrocardiographic changes including tented T waves, widening of the QRS complex and loss of P waves, sine wave pattern and eventually asystole. There have been only few reports of hyperkalemia causing ST segment elevation on electrocardiogram simulating an acute myocardial infarction. This case describes pseudo-myocardial infarction due to hyperkalemia and septic shock. Rapid determination of serum potassium levels by bedside blood gas analyzers serves to be a useful guide. ST segment elevation related to hyperkalemia will resolve with successful reduction of the serum potassium levels by appropriate therapy. It is important for physicians to be aware of this condition as this will aid in initiating correct therapy and prevent the patient from unnecessary interventions and the associated risk of complications. PMID- 25121384 TI - An unusual complication of stroke thrombolysis. PMID- 25121385 TI - Understanding correlation in the context of outliers. PMID- 25121387 TI - Esophageal perforation and death following glyphosate poisoning. PMID- 25121386 TI - Impact of midday meals- have all variables been considered? PMID- 25121388 TI - Paediatric malignant peripheral nerve sheath tumor with osteoid, rhabdomyosarcomatous, and liposarcomatous differentiation. PMID- 25121389 TI - Scalp hematoma: an atypical presentation of neurofibromatosis and a cause of hemorrhagic shock. PMID- 25121390 TI - Internal jugular vein medial to carotid artery. PMID- 25121392 TI - Pure yolk sac tumor of testis in an adult: a rare occurrence. PMID- 25121391 TI - Valgus deformity caused by dysplasia epiphysealis hemimelica in the knee. PMID- 25121393 TI - Dr. Vidya Acharya. PMID- 25121396 TI - Impairments due to injury, United States-1971. AB - During 1971 there were an estimated 12.5 million impairments of various types caused by injury based on data reported in the Health Interview Survey of the civilian population not confined to institutions. An impairment is a chronic or permanent defect, disabling or not, representing for the most part decrease or loss of ability to perform certain functions, particularly those of the musculoskeletal system and special senses. The originating cause, or etiology, is obtained for each impairment reported in the interview. Based on data collected in 1971 there were an estimated 51.1 million impairments reported in household interviews in response to the list of impairments on the questionnnaire or in response to questions about conditions causing disability or medical attention, of which 24.6 percent were reported as having been caused by injury. The report, "Impairments Due to Injury by Class and Type of Accident, United States, July 1959-June 1961," (Series 10, No. 6) presented data quite similar to that in the present report. Among the 12.5 million impairments due to injury the most frequently reported type was impairment of back or spine (except paralysis) with an estimated prevalence of 3.1 million cases The second most frequently reported type was impairment of lower extremity or hip (except paralysis or absence) with an estimate of 2.7 million. An estimated 29.3 percent of all impairments due to injury caused some degree of limitation of activity. About 25.4 percent of all impairments due to injury resulted from accidents in the home; 29.3 percent resulted from- injury occurring while at work; 17.8 percent resulted from moving motor vehicle accidents; and 20 percent resulted from some type of fall. PMID- 25121394 TI - Efficacy of electronic portable assistive devices for people with acquired brain injury: a systematic review. AB - A systematic review was conducted to evaluate the efficacy of electronic portable assistive devices (EPADs) for people with acquired brain injury. A systematic database search (OVID, CINAHL) found 541 citations published between 1989 and the end of 2012. A total of 23 reports met the inclusion/exclusion criteria, namely intervention studies (group, n-of-1) testing the efficacy of EPADs as compensatory devices for cognitive impairment for people with acquired brain injury aged 16-65 years. Study quality was rated by the PEDro (Physiotherapy Evidence Database) scale, (randomised controlled trials), the Downes and Black tool (other group intervention studies), and the Single Case Experimental Design tool (single participant studies). Levels of evidence were determined using five levels of classification based on the Spinal Cord Injury Rehabilitation Evidence table. Results found no Level 1 studies (RCTs with PEDro score >= 6), four Level 2 studies and 10 Level 3 studies. There was insufficient evidence to recommend any practice standards, but sufficient evidence to recommend the use of electronic reminder systems in supporting the everyday functioning of people with acquired brain injury as a practice guideline. Higher quality studies are required to support a broader range of compensatory roles that EPADs have the potential to play in neurorehabilitation and the long-term support of people with acquired brain injury. PMID- 25121395 TI - Design, synthesis, and evaluation of multitarget-directed selenium-containing clioquinol derivatives for the treatment of Alzheimer's disease. AB - A series of selenium-containing clioquinol derivatives were designed, synthesized, and evaluated as multifunctional anti-Alzheimer's disease (AD) agents. In vitro examination showed that several target compounds exhibited activities such as inhibition of metal-induced Abeta aggregation, antioxidative properties, hydrogen peroxide scavenging, and the prevention of copper redox cycling. A parallel artificial membrane permeation assay indicated that selenium containing clioquinol derivatives possessed significant blood-brain barrier (BBB) permeability. Compound 8a, with a propynylselanyl group linked to the oxine, demonstrated higher hydrogen peroxide scavenging and intracellular antioxidant activity than clioquinol. Furthermore, 8a exhibited significant inhibition of Cu(II)-induced Abeta1-42 aggregation and was capable of disassembling the preformed Cu(II)-induced Abeta aggregates. Therefore, 8a is an excellent multifunctional promising compound for development of novel drugs for AD. PMID- 25121398 TI - A new entry to asymmetric platinum(IV) complexes via oxidative chlorination. AB - Pt(IV) complexes are usually prepared by oxidation of the corresponding Pt(II) counterparts, typically using hydrogen peroxide or chlorine. A different way to synthesize asymmetrical Pt(IV) compounds is the oxidative chlorination of Pt(II) counterparts with N-chlorosuccinimide. The reaction between cisplatin cis [PtCl2(NH3)2], carboplatin, cis-[PtCl2(dach)] and cis-[Pt(cbdc)(dach)] (cbdc = cyclobutane-1,1'-dicarboxylato; dach = cyclohexane-1R,2R-diamine) with N chlorosuccinimide in ethane-1,2-diol was optimized to produce the asymmetric Pt(IV) octahedral complexes [PtA2Cl(glyc)X2] (A2 = 2 NH3 or dach; glyc = 2 hydroxyethanolato; X2 = 2 Cl or cbdc) in high yield and purity. The X-ray crystal structure of the [Pt(cbdc)Cl(dach)(glyc)] complex is also reported. Moreover, the oxidation method proved to be versatile enough to produce other mixed Pt(IV) derivatives varying the reaction medium. The two trichlorido complexes easily undergo a pH-dependent hydrolysis reaction, whereas the dicarboxylato compounds are stable enough to allow further coupling reactions for drug targeting and delivery via the glyc reactive pendant. Therefore, the coupling reaction between the [Pt(cbdc)Cl(dach)(glyc)] and a model carboxylic acid, a model amine, and selectively protected amino acids is reported. PMID- 25121397 TI - ProSeal Laryngeal Mask Airway Attenuates Systemic and Cerebral Hemodynamic Response During Awakening of Neurosurgical Patients: A Randomized Clinical Trial. AB - BACKGROUND: Extubation and emergence from anesthesia may lead to systemic and cerebral hemodynamic changes that endanger neurosurgical patients. We aimed to compare systemic and cerebral hemodynamic variables and cough incidence in neurosurgery patients emerging from general anesthesia with the standard procedure (endotracheal tube [ETT] extubation) or after replacement of the ETT with a laryngeal mask airway (LMA). MATERIALS AND METHODS: Forty-two patients undergoing supratentorial craniotomy under general anesthesia were included in a randomized open-label parallel trial. Patients were randomized (sealed envelopes labeled with software-generated randomized numbers) to awaken with the ETT in place or after its replacement with a ProSeal LMA. We recorded mean arterial pressure as the primary endpoint and heart rate, middle cerebral artery flow velocity, regional cerebral oxygen saturation, norepinephrine plasma concentrations, and coughing. RESULTS: No differences were found between groups at baseline. All hemodynamic variables increased significantly from baseline in both groups during emergence. The ETT group had significantly higher mean arterial pressure (11.9 mm Hg; 95% confidence interval [CI], 2.1-21.8 mm Hg) (P=0.017), heart rate (7.2 beats/min; 95% CI, 0.7-13.7 beats/min) (P=0.03), and rate-pressure product (1045.4; 95% CI, 440.8-1650) (P=0.001). Antihypertensive medication was administered to more ETT-group patients than LMA-group patients (9 [42.9%] vs. 3 [14.3%] patients, respectively; P=0.04). The percent increase in regional cerebral oxygen saturation was greater in the ETT group by 26.1% (95% CI, 9.1%-43.2%) (P=0.002), but no between-group differences were found in MCA flow velocity. Norepinephrine plasma concentrations rose in both groups between baseline and the end of emergence: LMA: from 87.5+/-7.1 to 125.6+/-17.3 pg/mL; and ETT: from 118.1+/-14.1 to 158.1+/-24.7 pg/mL (P=0.007). The differences between groups were not significant. The incidence of cough was higher in the ETT group (87.5%) than in the LMA group (9.5%) (P<0.001). CONCLUSIONS: Replacing the ETT with the LMA before neurosurgical patients emerge from anesthesia results in a more favorable hemodynamic profile, less cerebral hyperemia, and a lower incidence of cough. PMID- 25121399 TI - Effects of mycoplasmal upper-respiratory-tract disease on movement and thermoregulatory behavior of gopher tortoises (Gopherus polyphemus) in Georgia, USA. AB - Abstract From 2011-12, we studied a gopher tortoise (Gopherus polyphemus) population with a historically high prevalence of antibodies to Mycoplasma agassizii to assess long-term effects of upper-respiratory-tract disease (URTD) on tortoise behavior. We radiotracked 30 adult tortoises (16 males, 14 females) from a long-term study site with the use of mark-recapture methods to determine site fidelity and to compare home-range size to that of a study in 1997. An additional 10 tortoises (six males, four females) with severe clinical signs of URTD from elsewhere in the study area were radiotracked and compared to tortoises that were asymptomatic or had only mild clinical signs. We also monitored thermoregulatory behavior of tortoises with the use of data loggers affixed to the carapace. There was no significant difference in home-range size between the asymptomatic tortoises and those with mild symptoms. Home ranges of tortoises with severe URTD were significantly larger than asymptomatic or mildly affected tortoises. Tortoises with severe clinical signs moved long distances over short periods, contradicting a hypothesis that chronically infected tortoises are less likely to emigrate. Prevalence of M. agassizii antibodies was similar among the three groups (98% overall), but prevalence of antibodies to a second pathogen associated with URTD, Mycoplasma testudineum, was lower in the asymptomatic (n=14, 7%) and mild-symptoms (n=7, 14%) groups than the severe-symptoms group (n=8, 50%). Variation in the average carapacial temperatures of tortoises with severe URTD was significantly different from carapacial temperatures of mild and asymptomatic tortoises, suggesting differences in thermoregulatory behavior of severely ill tortoises. Our 15-yr recapture data suggest that, despite high prevalence of M. agassizii, population density has not decreased over time. However, emigration, especially of tortoises with severe clinical disease, may play an important role in dispersal and persistence of pathogens. PMID- 25121400 TI - Molecular methods to detect Mycoplasma spp. And Testudinid herpesvirus 2 in desert tortoises (Gopherus agassizii) and implications for disease management. AB - Abstract Mycoplasmas are an important cause of upper respiratory tract disease (URTD) in desert tortoises (Gopherus agassizii) and have been a main focus in attempts to mitigate disease-based population declines. Infection risk can vary with an animal's population of origin, making screening tests popular tools for determining infection status in individuals and populations. To provide additional methods for investigating URTD we developed quantitative PCR (qPCR) assays specific for agents causing clinical signs of URTD: Mycoplasma agassizii, Mycoplasma testudineum, and Testudinid herpesvirus 2 (TeHV2) and tested necropsied desert tortoises housed at the Desert Tortoise Conservation Center in Las Vegas, Nevada, USA, as well as wild desert tortoises (n=3), during 2010. Findings were compared with M. agassizii enzyme-linked immunosorbent assay (ELISA) data. Based on qPCR, the prevalence of M. agassizii was 75% (33/44) and the prevalence of TeHV2 was 48% (20/42) in the evaluated population. Both agents were also present in the wild tortoises. Mycoplasma testudineum was not detected. The M. agassizii ELISA and qPCR results did not always agree. More tortoises were positive for M. agassizii by nasal mucosa testing than by nasal flush. Our findings suggest that mycoplasmas are not the only agents of concern and that a single M. agassizii ELISA or nasal flush qPCR alone failed to identify all potentially infected animals in a population. Caution should be exercised in using these tests for disposition decisions. PMID- 25121401 TI - Baseline cutaneous bacteria of free-living New Zealand native frogs (Leiopelma archeyi and Leiopelma hochstetteri) and implications for their role in defense against the amphibian chytrid (Batrachochytrium dendrobatidis). AB - Abstract Knowledge of baseline cutaneous bacterial microbiota may be useful in interpreting diagnostic cultures from captive sick frogs and as part of quarantine or pretranslocation disease screening. Bacteria may also be an important part of innate immunity against chytridiomycosis, a fungal skin disease caused by Batrachochytrium dendrobatidis (Bd). In February 2009, 92 distinct bacterial isolates from the ventral skin of 64 apparently healthy Leiopelma archeyi and Leiopelma hochstetteri native frogs from the Coromandel and Whareorino regions in New Zealand were identified using molecular techniques. The most-common isolates identified in L. archeyi were Pseudomonas spp. and the most common in L. hochstetteri were Flavobacterium spp. To investigate the possible role of bacteria in innate immunity, a New Zealand strain of Bd (Kaikorai Valley Lewingii-2008-SDS1) was isolated and used in an in vitro challenge assay to test for inhibition by bacteria. One bacterial isolate, a Flavobacterium sp., inhibited growth of Bd. These results imply that diverse cutaneous bacteria are present and may play a role in the innate defense in Leiopelma against pathogens, including Bd, and are a starting point for further investigation. PMID- 25121402 TI - Are passerine birds reservoirs for influenza A viruses? AB - Abstract Although peridomestic passerine species have been involved in influenza A virus (IAV) outbreaks in poultry, there is little evidence to indicate they serve as reservoirs for these viruses under natural conditions. Recent molecular based detections of IAV in terrestrial wild birds have challenged this paradigm, and it has been suggested that additional research is warranted to better define the role of these birds as IAV hosts. To address this need, we reviewed the published literature reporting results from IAV surveillance of passerines. We also conducted prospective virologic and serologic surveillance of North American passerines for IAVs. The literature review included 60 publications from 1975 2013 that reported results from 829 species of passerines and other terrestrial birds. In our prospective study during 2010 and 2011, 3,868 serum samples and 900 swab samples were collected and tested from 102 terrestrial wild bird species from Georgia, New Jersey, Delaware, and Minnesota, USA. Antibodies to the nucleoprotein of IAV were detected with a commercial blocking enzyme-linked immunosorbent assay in 4/3,868 serum samples (0.1%); all positive samples were from Minnesota. No virus was detected in 900 swab samples by virus isolation in embryonated chicken eggs or matrix real-time reverse transcriptase PCR. Our results are consistent with historic literature; although passerines and terrestrial wild birds may have a limited role in the epidemiology of IAV when associated with infected domestic poultry or other aberrant hosts, there is no evidence supporting their involvement as natural reservoirs for IAV. PMID- 25121403 TI - An alternative interpretation of plasma selenium data from endangered patagonian huemul deer (Hippocamelus bisulcus). PMID- 25121405 TI - Aprocta cylindrica (Nematoda) infection in a European Robin (Erithacus rubecula) in Britain. AB - A European Robin (Erithacus rubecula) found dead in England had marked blepharitis and periocular alopecia associated with Aprocta cylindrica (Nematoda: Aproctidae) and concurrent mixed fungal infections. Aprocta cylindrica should be considered a differential diagnosis in periocular abnormalities of robins and other insectivorous, migratory passerines in Western Europe. PMID- 25121406 TI - European mustelids occupying pristine wetlands in the Danube Delta are infected with Trichinella likely derived from domesticated swine. AB - Abstract We analyzed 32 specimens from nine species of Mustelidae for Trichinella; six infections from two Trichinella species were observed from three host species. This provides documentation of Trichinella in Mustela erminea and Martes foina in Romania and Trichinella spiralis in a mustelid host from Europe. Trichinella spiralis continues to be a public challenge characterized by a wide host range and geographical distribution ( Pozio 2007 ). During the past 20 yr, Romania has had the most reported human cases of trichinellosis in the world ( Blaga et al. 2007 ). Transmission occurs among domesticated swine, rats, and wild mammals that feed by scavenging or predation ( Pozio 2000 ). Trichinella transmission to humans may occur by consumption of meat of livestock infected after exposure to wildlife ( Pozio et al. 2009 ). PMID- 25121404 TI - Novel combinations of nalbuphine and medetomidine for wildlife immobilization. AB - We formulated novel drug combinations of nalbuphine HCl and medetomidine HCl (NalMed), with or without azaperone tartrate, for use in immobilizing Rocky Mountain elk (Cervus elaphus nelsoni) and potentially for other wildlife species. Using the lowest tested nalbuphine dose (0.3 mg/kg) that produced sedation in elk, we initially evaluated a combination of nalbuphine, medetomidine, and azaperone (NalMed-A) for immobilizing adult elk. Based on initial success, we then conducted follow-up trials to assess alternative NalMed formulations successively modified to improve field usability, striving to shorten induction within a dose volume that accommodated practical remote delivery. All NalMed formulations immobilized adult elk; however, combinations with dose volumes that included about 80 mg nalbuphine tended to yield the shortest inductions (mean 6.8 min with, and 7.7 min without, azaperone). Our findings demonstrate that nalbuphine and medetomidine can be combined to yield effective, low-volume (<= 2 mL), lightly regulated, reversible drug combinations. Based on results to date, we recommend NalMed-A (40 mg/mL nalbuphine, 10 mg/mL medetomidine, and 10 mg/mL azaperone) dosed at 1.8-2.0 mL for immobilizing adult elk; for recovery we recommend 50 mg naltrexone and 600 mg tolazoline administered intramuscularly (IM) about 5 min in advance of 100 mg atipamezole (divided 25 mg intravenously and 75 mg IM). Further work is under way to explore efficacy in other large mammal species. PMID- 25121407 TI - Pathogen infection and exposure, and ectoparasites of the federally endangered Amargosa vole (Microtus californicus scirpensis), California, USA. AB - Abstract We surveyed pathogens and ectoparasites among federally endangered Amargosa voles (Microtus californicus scirpensis) and sympatric rodents in Tecopa Hot Springs, Inyo County, California, December 2011-November 2012. We aimed to assess disease and detect possible spillover from or connectivity with other hosts within and outside the Amargosa ecosystem. We assessed 71 individual voles and 38 individual sympatric rodents for current infection with seven vector-borne zoonotic pathogens and past exposure to five pathogens. Thirteen percent of Amargosa voles were PCR positive for Toxoplasma gondii, a zoonotic protozoan that may alter host behavior or cause mortality. Additionally, we found antibodies against Borrelia burgdorferi sensu lato (SL) spp. in 21% of voles, against Anaplasma phagocytophilum in 2.6%, Rickettsia spp. in 13%, relapsing fever Borrelia (3.9%), and T. gondii (7.9%). Sympatric rodents also had active infections with Borrelia SL spp. (15%). Of the ectoparasites collected, the tick Ixodes minor is of particular interest because the study area is well outside of the species' reported range and because I. minor ticks infest migratory birds as well as rodents, showing a potential mechanism for pathogens to be imported from outside the Amargosa ecosystem. PMID- 25121408 TI - Serologic survey for cross-species pathogens in urban coyotes (Canis latrans), Colorado, USA. AB - Abstract As coyotes (Canis latrans) adapt to living in urban environments, the opportunity for cross-species transmission of pathogens may increase. We investigated the prevalence of antibodies to pathogens that are either zoonotic or affect multiple animal species in urban coyotes in the Denver metropolitan area, Colorado, USA, in 2012. We assayed for antibodies to canine parvovirus-2, canine distemper virus, rabies virus, Toxoplasma gondii, Yersinia pestis, and serotypes of Leptospira interrogans. Overall, 84% of the animals had antibodies to canine parvovirus-2, 44% for canine distemper virus, 20% for T. gondii (IgG), 28% for Y. pestis, and 4% for L. interrogans serotype Grippotyphosa. No neutralizing antibodies were detected to rabies virus, T. gondii (IgM), or L. interrogans serotypes other than Grippotyphosa. With 88% of animals exposed to at least one pathogen, our results suggest that coyotes may serve as important reservoirs and sentinels for etiologic agents. PMID- 25121410 TI - Detection and molecular characterization of a reovirus in black-capped chickadees (Poecile atricapillus) from Minnesota, USA. AB - In 2011, the Minnesota Rehabilitation Center submitted four dead Black-capped Chickadees (Poecile atricapillus) for necropsy to the Minnesota Veterinary Diagnostic Laboratory. All four chickadees were underweight and dehydrated and their intestinal contents were watery and yellowish. No significant lesions were observed upon histopathologic examination. Viral particles of the family Reoviridae were detected after negative-contrast electron microscopic examination of intestinal contents. Analysis by reverse transcriptase PCR and sequencing confirmed the presence of a reovirus. Based on phylogenetic analysis, the chickadee reovirus had 97.1% to 98.3% and 89.4% to 97.8% nucleotide identity with turkey enteric reoviruses from apparently healthy and enteritis-affected turkey poults, respectively. The chickadee reovirus had only 56.5% and 58.5% nucleotide and 54.5% and 56.8% amino acid identity with psittacine reovirus and Tvarminne avian virus, respectively. These results indicate that the chickadee reovirus is closely related to turkey reoviruses. PMID- 25121409 TI - Relatively high prevalence of pox-like lesions in Henslow's sparrow (Ammodrammus henslowii) among nine species of migratory grassland passerines in Wisconsin, USA. AB - Globally, Avipoxvirus species affect over 230 species of wild birds and can significantly impair survival. During banding of nine grassland songbird species (n=346 individuals) in southwestern Wisconsin, USA, we noted species with a 2-6% prevalence of pox-like lesions (possible evidence of current infection) and 4-10% missing digits (potential evidence of past infection). These prevalences approach those recorded among island endemic birds (4-9% and 9-20% for the Galapagos and Hawaii, respectively) for which Avipoxvirus species have been implicated as contributing to dramatic population declines. Henslow's Sparrow Ammodramus henslowii (n=165 individuals) had the highest prevalence of lesions (6.1%) and missing digits (9.7%). Among a subset of 26 Henslow's Sparrows from which blood samples were obtained, none had detectable antibody reactive to fowlpox virus antigen. However, four samples (18%) had antibody to canarypox virus antigen with test sample and negative control ratios (P/N values) ranging from 2.4 to 6.5 (median 4.3). Of four antibody-positive birds, two had lesions recorded (one was also missing a digit), one had digits missing, and one had no signs. Additionally, the birds with lesions or missing digits had higher P/N values than did the antibody-positive bird without missing digits or recorded lesions. This study represents an impetus for considering the impacts and dynamics of disease caused by Avipoxvirus among North American grassland bird species. PMID- 25121411 TI - Rabies in the insectivorous Pallas's mastiff bat (Molossus molossus) in northeastern Brazil. AB - We describe the pathologic and immunohistochemical findings in five cases of rabies in the insectivorous Pallas's mastiff bat (Molossus molossus) in the city of Patos, state of Paraiba, northeastern Brazil. All cases were found during the day, in different neighborhoods, prostrate and unable to fly. No significant lesions were observed at necropsy or on histologic examination. The brains of the five bats showed strong immunohistochemical labeling for rabies virus in the form of large corpuscles or multiple clusters of granules within the perikarya of neurons in different areas of the brain, mainly in the cerebral cortex and cerebellar Purkinje cells. Three bats tested by direct immunofluorescence and mouse inoculation were also positive for rabies. These data demonstrate that M. molossus may be infected with the rabies virus and develop rabies, even without histologic lesions in the central nervous system, and can be a source of infection for humans and domestic animals. PMID- 25121412 TI - Asymmetric synthesis of chiral heterocyclic amino acids via the alkylation of the Ni(II) complex of glycine and alkyl halides. AB - An investigation into the reactivity profile of alkyl halides has led to the development of a new method for the asymmetric synthesis of chiral heterocyclic amino acids. This protocol involves the asymmetric alkylation of the Ni(II) complex of glycine to form an intermediate, which then decomposes to form a series of valuable chiral amino acids in high yields and with excellent diastereoselectivity. The chiral amino acids underwent a smooth intramolecular cyclization process to afford the valuable chiral heterocyclic amino acids in high yields and enantioselectivities. This result paves the way for the development of a new synthetic method for chiral heterocyclic amino acids. PMID- 25121414 TI - Breast reconstruction and medical necessity. PMID- 25121413 TI - Maximum standardized uptake value on 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography and glucose transporter-1 expression correlates with survival in invasive ductal carcinoma of the pancreas. AB - OBJECTIVES: The purpose of this study was to assess the correlations among the maximum standardized uptake value (SUVmax) on 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT); the expressions of glucose transporter 1 (GLUT-1), glucose transporter 3, and epidermal growth factor receptor (EGFR); as well as prognosis in patients with invasive ductal carcinoma of the pancreas. METHODS: A total of 41 patients with surgically resected and histologically proven invasive ductal carcinoma of the pancreas who underwent preoperative FDG-PET/CT were assessed. The SUVmax at the primary tumor site was measured by FDG-PET/CT, and immunohistochemical staining of tumor sections was performed for GLUT-1, glucose transporter 3, and EGFR. RESULTS: Higher FDG uptake (SUVmax, >3.40) and GLUT-1 expression were significantly associated with shorter overall survival (P < 0.05). The SUVmax was not found to be significantly correlated with clinicopathological characteristics such as TNM classification, lymph node metastasis, and tumor differentiation. The EGFR expression was significantly correlated with the SUVmax (P = 0.024). CONCLUSIONS: Higher FDG uptake and GLUT-1 expression in invasive ductal carcinoma of the pancreas seems to be an important prognostic factor. In addition, the EGFR expression was significantly correlated with the SUVmax. PMID- 25121415 TI - Dakin's solution: historical perspective and current practice. AB - Dakin's solution was first introduced by military physicians responding to the challenges of treating artillery injuries in World War I. Administration was personnel intensive, and at times unpredictable in the conditions of the frontlines, but nonetheless the practice saved countless lives and limbs. Dakin's solution remained the prevailing method for treating contaminated wounds until the introduction of antibiotics during World War II. With the emergence of antibiotic-resistant organisms in the 1980s, interest in antiseptic treatment of wounds resurfaced; especially in chronic wounds, antiseptics once again saw liberal use. However, as the understanding of wound healing advanced, focus shifted from "prevention of infection" to "creation of an optimal environment for the repair process." Concern that antiseptics could be toxic to the cells of the repair process has led many to discontinue their use. Although such all-or-none approaches might simplify the decision-making process, they fail to address the complexity of optimal wound management. As recent research suggests, there may be a renewed role for Dakin's solution. PMID- 25121416 TI - Lessons learned from the first quadruple extremity transplantation in the world. AB - BACKGROUND: Limb transplantation is emerging as a promising area of surgery and is an indispensable alternative for prosthetic rehabilitation of amputees, the severity of which is increasing because of combat-related injuries. Successful unilateral and bilateral limb transplantations have already been performed before this operation. METHODS: We performed the first ever quadruple limb transplantation in February 2012. The limbs procured from a 40-year-old man heart beating donor were transplanted to a 27-year-old male patient who was a quadruple amputee for the last 14 years because of an electrical injury. RESULTS: To shorten the ischemic period to a minimum, 3 separate microsurgery teams worked simultaneously. All extremities were reperfused within 8 hours of procurement, and the operation lasted for 12 hours. Metabolic load was managed by hemodialysis. One hour after the completion of the operation, cardiac arrest developed, resuscitation of which necessitated median sternotomy and temporary partial cardiopulmonary support. Despite the removal of the transplanted limbs and all efforts including continuous hemodialysis, plasmapheresis, and extracorporeal membrane oxygenation, the patient died on the fourth day after transplantation in a clinical condition of severe systemic inflammation. CONCLUSIONS: The problems we faced were difficulty of vascular access for invasive monitoring and fluid replacement, and the severe systemic inflammation effects of which could not be dealt with, despite aggressive supportive treatment. We hope that our experience will enlighten the surgeons who are willing to extend the limits of limb transplantation and serve the success of future operations. PMID- 25121417 TI - Discussion of lessons learned from the first quadruple extremity transplantation in the world: the logic of massive allograft transplantation. PMID- 25121418 TI - Congenital nail abnormalities: a review of the literature. AB - Congenital nail abnormalities (CNAs) are rare conditions in which the nail tissue appears abnormal compared with the fingers and the toes. They usually present accompanying deformities and disorders. Our purpose was to review the current literature on the clinical aspects of CNA. We reviewed the literature to evaluate peer-reviewed articles on the topic. Detailed reports have characterized many types of CNA. In this article, we provide a review of the literature based on the current understanding of CNAs and the clinical varieties thereof. PMID- 25121419 TI - The forehead flap for immediate reconstruction of the nose after bite injuries: indications, advantages, and disadvantages. PMID- 25121420 TI - Fat graft survival: physics matters: invited commentary to "The impact of liposuction cannula size on adipocyte viability". PMID- 25121421 TI - Applications of algorithmic differentiation to phase retrieval algorithms. AB - In this paper, we generalize the techniques of reverse-mode algorithmic differentiation to include elementary operations on multidimensional arrays of complex numbers. We explore the application of the algorithmic differentiation to phase retrieval error metrics and show that reverse-mode algorithmic differentiation provides a framework for straightforward calculation of gradients of complicated error metrics without resorting to finite differences or laborious symbolic differentiation. PMID- 25121422 TI - Characteristic functions describing the power absorption response of periodic structures to partially coherent fields. AB - Periodic thin-film structures are widely used as absorptive structures for electromagnetic radiation. We show that the absorption behavior for partially coherent illumination can be fully characterized by a set of characteristic functions in wavenumber space. We discuss the prediction of these functions using electromagnetic solvers based on periodic boundary conditions, and their measurement experimentally using Energy Absorption Interferometry (EAI). The theory is developed here for the case of 2D absorbers with TE illumination and arbitrary material properties in the plane of the problem, except for the resistivity, which is assumed isotropic. Numerical examples are given for the case of absorbing strips printed on a semi-infinite substrate. We derive rules for the convergence of the representation as a function of the number of characteristic functions used, as well as conditions for sampling in EAI experiments. PMID- 25121423 TI - Compressed sampling strategies for tomography. AB - We investigate new sampling strategies for projection tomography, enabling one to employ fewer measurements than expected from classical sampling theory without significant loss of information. Inspired by compressed sensing, our approach is based on the understanding that many real objects are compressible in some known representation, implying that the number of degrees of freedom defining an object is often much smaller than the number of pixels/voxels. We propose a new approach based on quasi-random detector subsampling, whereas previous approaches only addressed subsampling with respect to source location (view angle). The performance of different sampling strategies is considered using object independent figures of merit, and also based on reconstructions for specific objects, with synthetic and real data. The proposed approach can be implemented using a structured illumination of the interrogated object or the detector array by placing a coded aperture/mask at the source or detector side, respectively. Advantages of the proposed approach include (i) for structured illumination of the detector array, it leads to fewer detector pixels and allows one to integrate detectors for scattered radiation in the unused space; (ii) for structured illumination of the object, it leads to a reduced radiation dose for patients in medical scans; (iii) in the latter case, the blocking of rays reduces scattered radiation while keeping the same energy in the transmitted rays, resulting in a higher signal-to-noise ratio than that achieved by lowering exposure times or the energy of the source; (iv) compared to view-angle subsampling, it allows one to use fewer measurements for the same image quality, or leads to better image quality for the same number of measurements. The proposed approach can also be combined with view-angle subsampling. PMID- 25121424 TI - Generation of hollow beam with radially polarized vortex beam and complex amplitude filter. AB - The generation of hollow beams with a long focal depth from a radially polarized Bessel-Gaussian beam with a second-order vortex phase and an amplitude filter is theoretically investigated by Richards-Wolf's integral. The null intensity on the optical axis is achieved by introducing the second-order vortex. The long focal depth is a result of the amplitude filtering based on the cosine function and Euler transformation. Numerical results indicate that the focal depth of a hollow beam is improved from 0.96lambda to 2.28lambda with a slight increase of the transverse size for the simplest amplitude filter design. The intensity distribution twist phenomenon of the x- and y-polarized components around the optical axis due to the introducing of the vortex phase is also discussed. It is believed that the proposed scheme can be used to achieve particle acceleration and optical trapping. PMID- 25121425 TI - High-precision rotation angle measurement method based on monocular vision. AB - To accurately measure the attitude angles (pitch, roll, and yaw) of a rigid object that rotates in a space, we propose a high-precision rotation angle measurement method based on monocular vision. This method combines camera self calibration, multiview geometry, and 3D measurement. This monocular vision measuring system consists of an area scan CCD, a prime lens, and a spots array target, which are fixed on the measured object. We can calculate the rotation angle according to the rebuilt rotating spots array target by using this monocular vision measuring system. The measurement precision of rotation angle can reach 1 arc sec in this paper's experiments. This method has high measurement precision and good stability. Therefore we can widely use this method in machinery manufacturing, engineering measurement, aerospace, and the military. PMID- 25121426 TI - Computational aspects of the through-focus characteristics of the human eye. AB - Calculating through-focus characteristics of the human eye from a single objective measurement of wavefront aberration can be accomplished through a range of methods that are inherently computationally cumbersome. A simple yet accurate and computationally efficient method is developed, which combines the philosophy of the extended Nijboer-Zernike approach with the radial-basis-function-based approximation of the complex pupil function. The main advantage of the proposed technique is that the increase of the computational cost for a vector-valued defocus parameter is practically negligible in comparison to the corresponding scalar-valued defocus parameter. PMID- 25121427 TI - Diffraction by a frustrated system: the triangular Ising antiferromagnet. AB - Expressions are derived for diffraction by the triangular Ising antiferromagnet, a disordered lattice system consisting of two kinds of scatterer and exhibiting geometric frustration. Analysis of the expressions shows characteristics of the diffraction patterns, including the presence of Bragg and diffuse diffraction, superlattice reflections, and their behavior with temperature. These characteristics are illustrated by numerical simulations. The results have application to diffraction imaging of disordered systems. PMID- 25121428 TI - Optimization for calibration of large-scale optical measurement positioning system by using spherical constraint. AB - The measurement accuracy of a large-scale optical measurement positioning system largely depends on the calibration procedure. A more reliable calibration approach for the system by using spherical constraints is presented in this paper, and both the adjustment model based on spherical constraint and the calculation method for the optimization are given. This approach can provide constraint in every direction of the system in the workspace and thereby estimate the orientation parameters more accurately than by using current methods. The experimental data show that by using the proposed method, which improves the accuracy of the depth direction, the average 3D coordinate error of the system compared with the laser tracker is about 0.18 mm in the whole workspace. PMID- 25121429 TI - Quantitative analysis of imperfect frequency multiplying in fractional Talbot planes and its effect on high-frequency-grating lithography. AB - Fractional Talbot images of amplitude line gratings, with small opening slits compared to the period, are characterized by an integer multiple of the gratings' spatial frequency. We investigate the formation of fractional Talbot images analytically within a scalar framework and give a comprehensible insight into the paraxial limits involved. Particular attention is paid to nonparaxial effects on the intensity distribution at fractional Talbot planes and their lateral periodicities. We present a comparison between the measured intensity distributions and a numerical implementation of our analytical method. Both ways reveal the paraxial limits of frequency multiplication on fractional Talbot images. The use of fractional Talbot images for lithography results in ghost diffraction orders. We roughly estimate the ghost orders quantitatively with a simple numerical model for monochromatic and polychromatic illumination. PMID- 25121430 TI - Outlier modeling for spectral data reduction. AB - The spectra in spectral reflectance datasets tend to be quite correlated and therefore they can be represented more compactly using standard techniques such as principal components analysis (PCA) as part of a lossy compression strategy. However, the presence of outlier spectra can often increase the overall error of the reconstructed spectra. This paper introduces a new outlier modeling (OM) method that detects, clusters, and separately models outliers with their own set of basis vectors. Outliers are defined in terms of the robust Mahalanobis distance using the fast minimum covariance determinant algorithm as a robust estimator of the multivariate mean and covariance from which it is computed. After removing the outliers from the main dataset, the performance of PCA on the remaining data improves significantly; however, since outlier spectra are a part of the image, they cannot simply be ignored. The solution is to cluster the outliers into a small number of clusters and then model each cluster separately using its own cluster-specific PCA-derived bases. Tests show that OM leads to lower spectral reconstruction errors of reflectance spectra in terms of both normalized RMS and goodness of fit. PMID- 25121431 TI - Combining local binary patterns and local color contrast for texture classification under varying illumination. AB - This paper presents a texture descriptor for color texture classification specially designed to be robust against changes in the illumination conditions. The descriptor combines a histogram of local binary patterns (LBPs) with a novel feature measuring the distribution of local color contrast. The proposed descriptor is invariant with respect to rotations and translations of the image plane and with respect to several transformations in the color space. We evaluated the proposed descriptor on the Outex test suite, by measuring the classification accuracy in the case in which training and test images have been acquired under different illuminants. The results obtained show that our descriptor outperforms the original LBP approach and its color variants, even when these are computed after color normalization. Moreover, it also outperforms several other color texture descriptors in the state of the art. PMID- 25121432 TI - Structural design and characteristics of dual-mode fibers with equalized group velocity. AB - We investigate how the index profile of a few-mode fiber (FMF) can be designed so that group velocities of the two lowest-order modes can be equalized at a normalized frequency, which is below the cut-off frequency of the LP21 mode. This can be achieved using a single-clad power-law profile with a sufficiently large profile exponent or a double-clad profile consisting of a graded-core surrounded by a sufficiently thick depressed inner cladding without index jump at their interface. The fabrication tolerances, effective index differences, intramodal dispersion differences, and effective mode areas of various single- and double-clad profiles are compared. The results show that, in comparison to single-clad fibers, double-clad fibers are capable of producing higher fabrication tolerances and reduced sensitivity of group delay difference to wavelength by three and two orders of magnitude, respectively. Our analyses provide insights into the design of FMFs, which will facilitate future development of high-capacity mode division long-haul transmission systems. PMID- 25121433 TI - Dynamical deformed Airy beams with arbitrary angles between two wings. AB - We study both numerically and experimentally the acceleration and propagation dynamics of 2D Airy beams with arbitrary initial angles between their "two wings." Our results show that the acceleration of these generalized 2D Airy beams strongly depends on the initial angles and cannot be simply described by the vector superposition principle (except for the normal case of a 90 degrees angle). However, as a result of the "Hyperbolic umbilic" catastrophe (a two-layer caustic), the main lobes of these 2D Airy beams still propagate along parabolic trajectories even though they become highly deformed. Under such conditions, the peak intensity (leading energy flow) of the 2D Airy beams cannot be confined along the main lobe, in contrast to the normal 90 degrees case. Instead, it is found that there are two parabolic trajectories describing the beam propagation: one for the main lobe, and the other for the peak intensity. Both trajectories can be readily controlled by varying the initial wing angle. Due to their self healing property, these beams tend to evolve into the well-known 1D or 2D Airy patterns after a certain propagation distance. The theoretical analysis corroborates our experimental observations, and explains clearly why the acceleration of deformed Airy beams increases with the opening of the initial wing angle. PMID- 25121434 TI - Analysis of Fibonacci gratings and their diffraction patterns. AB - Aperiodic and fractal optical elements are proving to be promising candidates in image-forming devices. In this paper, we analyze the diffraction patterns of Fibonacci gratings (FbGs), which are prototypical examples of aperiodicity. They exhibit novel characteristics such as redundancy and robustness that keep their imaging characteristics intact even when there is significant loss of information. FbGs also contain fractal signatures and are characterized by a fractal dimension. Our study suggests that aperiodic gratings may be better than their fractal counterparts in technologies based on such architectures. We also identify the demarcating features of aperiodic and fractal diffraction, which have been rather fuzzy in the literature so far. PMID- 25121435 TI - Changing correlation into anticorrelation by superposing thermal and laser light. AB - Correlation can be changed into anticorrelation by superposing thermal and laser light with the same frequency and polarization. Two-photon interference theory is employed to interpret this phenomenon. An experimental scheme is designed to verify the theoretical predictions by employing pseudothermal light to simulate thermal light. The experimental results are consistent with the theoretical results. PMID- 25121436 TI - Temporal dark adaptation to spatially complex backgrounds: effect of an additional light source. AB - Visual adaptation (and especially dark adaptation) has been studied extensively in the past, however, mainly addressing adaptation to fully dark backgrounds. At this stage, it is unclear whether these results are not too simple to be applied to complex situations, such as predicting adaptation of a motorist driving at night. To fill this gap we set up a study investigating how spatially complex backgrounds influence temporal dark adaptation. Our results showed that dark adaptation to spatially complex backgrounds leads to much longer adaptation times than dark adaptation to spatially uniform backgrounds. We conclude therefore that the adaptation models based on past studies overestimate the visual system's sensitivity to detect luminance variations in spatially complex environments. Our results also showed large variations in adaptation times when varying the degree of spatial complexity of the background. Hence, we may conclude that it is important to take into account models that are based on spatially complex backgrounds when predicting dark adaptation for complex environments. PMID- 25121437 TI - Rayleigh approximation for the scattering of small partially charged sand particles. AB - Based on the Rayleigh approximation, this paper presents the electromagnetic scattering properties of the small partially charged isotropic sphere and those of a similar anisotropic sphere and then discusses the effect of surface charges on particles' optical properties. The numerical simulation results show that the surface charges on a charged particle can enhance the scattering of the incident waves, and the effect on an anisotropic charged sphere is much greater than that on an isotropic charged particle. Therefore it is necessary to consider the medium property (isotropic or anisotropic) and electric effects of dust particles in the remote sensing of sandstorms. PMID- 25121439 TI - Custom-modified three-dimensional periodic microstructures by pattern-integrated interference lithography. AB - By combining interference lithography and projection photolithography concurrently, pattern-integrated interference lithography (PIIL) enables the wafer-scale, rapid, and single-exposure fabrication of multidimensional periodic microstructures that integrate arbitrary functional elements. To date, two dimensional PIIL has been simulated and experimentally demonstrated. In this paper, we report new simulated results of PIIL exposures for various custom modified three-dimensional (3D) periodic structures. These results were generated using custom PIIL comprehensive vector modeling. Simulations include mask integrated and mask-shaped 3D periodic arrangements as well as microcavities on top of or fully embedded within 3D periodic structures. These results indicate PIIL is a viable method for making versatile 3D periodic microstructures. PMID- 25121438 TI - Corresponding color datasets and a chromatic adaptation model based on the OSA UCS system. AB - Today chromatic adaptation transforms (CATs) are reconsidered, since their mathematical inconsistency has been shown in Color Res. Appl.38, 188 (2013) and by the CIE technical committee TC 8-11: CIECAM02 Mathematics. In 2004-2005 the author proposed an adaptation transform based on the uniform color scale system of the Optical Society of America (OSA-UCS) [J. Opt. Soc. Am. A21, 677 (2004); Color Res. Appl. 30, 31 (2005)] that transforms the cone-activation stimuli into adapted stimuli. The present work considers all the 37 available corresponding color (CC) datasets selected by CIE and (1) shows that the adapted stimuli obtained from CC data are defined up to an unknown transformation, and an unambiguous definition of the adapted stimuli requires additional hypotheses or suitable experimental data (as it is in the OSA-UCS system); (2) produces a CAT, represented by a linear transformation between CCs, associated with any CC dataset, whose high quality measured in DeltaE units discards the possibility of nonlinear transformations; (3) analyzes these color-conversion matrices in a heuristic way with a reference adaptation that is approximately that of the OSA UCS adapted colors for the D65 illuminant and particularly shows accordance with the Hunt effect and the Bezold-Brucke hue shift; (4) proposes the measurements of CC stimuli with a reference adaptation equal to that of the visual situation of the OSA-UCS system for defining adapted colors for any considered illumination adaptation and therefore for defining a general CAT formula. PMID- 25121440 TI - Rapid computation of the amplitude and phase of tightly focused optical fields distorted by scattering particles. AB - We develop an efficient method for accurately calculating the electric field of tightly focused laser beams in the presence of specific configurations of microscopic scatterers. This Huygens-Fresnel wave-based electric field superposition (HF-WEFS) method computes the amplitude and phase of the scattered electric field in excellent agreement with finite difference time-domain (FDTD) solutions of Maxwell's equations. Our HF-WEFS implementation is 2-4 orders of magnitude faster than the FDTD method and enables systematic investigations of the effects of scatterer size and configuration on the focal field. We demonstrate the power of the new HF-WEFS approach by mapping several metrics of focal field distortion as a function of scatterer position. This analysis shows that the maximum focal field distortion occurs for single scatterers placed below the focal plane with an offset from the optical axis. The HF-WEFS method represents an important first step toward the development of a computational model of laser-scanning microscopy of thick cellular/tissue specimens. PMID- 25121441 TI - Unitary rotations in two-, three-, and D-dimensional Cartesian data arrays. AB - Using a previous technique to rotate two-dimensional images on an N*N square pixellated screen unitarily, we can rotate three-dimensional pixellated cubes of side N, and also generally D-dimensional Cartesian data arrays, also unitarily. Although the number of operations inevitably grows as N(2D) (because each rotated pixel depends on all others), and Gibbs-like oscillations are inevitable, the result is a strictly unitary and real transformation (thus orthogonal) that is invertible (thus no loss of information) and could be used as a standard. PMID- 25121443 TI - Pattern recognition based on the correlated intensity fluctuations of thermal light. AB - Here we present a pattern recognition scheme based on the intensity correlation of thermal light. We prove theoretically that under spatially incoherent illumination the matched filtering technique can be realized in the ghost imaging field. Using the matched filtering technique, it is possible to distinguish an object from a preestablished set of objects through their ghost images, which are extracted by means of intensity correlation measurement. According to the pattern recognition scheme, we present a numerical simulation in which we can easily identify the character inserted into the object arm from a set of two characters through the position of the autocorrelation peak. This pattern recognition scheme opens up the possibility of performing coherent optical processing under spatially incoherent illumination. PMID- 25121442 TI - Signal-to-noise ratio limitations for intensity correlation imaging. AB - Intensity correlation imaging (ICI) is a concept which has been considered for the task of providing images of satellites in geosynchronous orbit using ground based equipment. This concept is based on the intensity interferometer principle first developed by Hanbury Brown and Twiss. It is the objective of this paper to establish that a sun-lit geosynchronous satellite is too faint a target object to allow intensity interferometry to be used in developing image information about it-at least not in a reasonable time and with a reasonable amount of equipment. An analytic treatment of the basic phenomena is presented. This is an analysis of one aspect of the statistics of the very high frequency random variations of a very narrow portion of the optical spectra of the incoherent (black-body like actually reflected sunlight) radiation from the satellite, an analysis showing that the covariance of this radiation as measured by a pair of ground-based telescopes is directly proportional to the square of the magnitude of one component of the Fourier transform of the image of the satellite-the component being the one for a spatial frequency whose value is determined by the separation of the two telescopes. This analysis establishes the magnitude of the covariance. A second portion of the analysis considers shot-noise effects. It is shown that even with much less than one photodetection event (pde) per signal integration time an unbiased estimate of the covariance of the optical field's random variations can be developed. Also, a result is developed for the standard deviation to be associated with the estimated value of the covariance. From these results an expression is developed for what may be called the signal-to-noise ratio to be associated with an estimate of the covariance. This signal-to-noise ratio, it turns out, does not depend on the measurement's integration time, Deltat (in seconds), or on the optical spectral bandwidth, Deltanu (in Hertz), utilized-so long as DeltatDeltanu?1, which condition it would be hard to violate. It is estimated that for a D=3.16 m diameter satellite, with a pair of D=1.0 m diameter telescopes (which value of D probably represents an upper limit on allowable aperture diameter since the telescope aperture must be much too small to even resolve the size of the satellite) at least N=2.55*10(16) separate pairs of (one integration time, pde count) measurement values must be collected to achieve just a 10 dB signal-to-noise ratio. Working with 10 pairs of telescopes (all with the same separation), and with 10 nearly adjacent and each very narrow spectral bands extracted from the light collected by each of the telescope-so that for each measurement integration time there would be 100 pairs of measurement values available-and with an integration time as short as Deltat=1 ns, it would take T=2.55*10(5) s or about 71 h to collect the data for just a single spatial frequency component of the image of the satellite. It is on this basis that it is concluded that the ICI concept does not seem likely to be able to provide a timely responsive capability for the imaging of geosynchronous satellites. PMID- 25121444 TI - Scintillations of optical plane and spherical waves in underwater turbulence. AB - The scintillation indices of optical plane and spherical waves propagating in underwater turbulent media are evaluated by using the Rytov method, and the variations in the scintillation indices are investigated when the rate of dissipation of mean squared temperature, the temperature and salinity fluctuations, the propagation distance, the wavelength, the Kolmogorov microscale length, and the rate of dissipation of the turbulent kinetic energy are varied. Results show that as in the atmosphere, also in underwater media the plane wave is more affected by turbulence as compared to the spherical wave. The underwater turbulence effect becomes significant at 5-10 m for a plane wave and at 20-25 m for a spherical wave. The turbulence effect is relatively small in deep water and is large at the surface of the water. Salinity-induced turbulence strongly dominates the scintillations compared to temperature-induced turbulence. PMID- 25121445 TI - Angular and polarization response of multimode sensors with resistive-grid absorbers. AB - High-sensitivity receiver systems with near-ideal polarization sensitivity are highly desirable for development of millimeter and submillimeter radio astronomy. Multimoded bolometers provide a unique solution to achieve such sensitivity, for which hundreds of single-mode sensors would otherwise be required. The primary concern in employing such multimoded sensors for polarimetery is the control of the polarization systematics. In this work, we examine the angular- and polarization-dependent absorption pattern of a thin resistive grid or membrane, which models an absorber used for a multimoded bolometer. The result shows that a freestanding thin resistive absorber with a surface resistivity of eta/2, where eta is the impedance of free space, attains a beam pattern with equal E- and H plane responses, leading to zero cross-polarization. For a resistive-grid absorber, the condition is met when a pair of grids is positioned orthogonal to each other and both have a resistivity of eta/2. When a reflective backshort termination is employed to improve absorption efficiency, the cross-polar level can be suppressed below -30 dB if acceptance angle of the sensor is limited to ?60 degrees . The small cross-polar systematics have even-parity patterns and do not contaminate the measurements of odd-parity polarization patterns, for which many of the recent instruments for cosmic microwave background are designed. Underlying symmetry that suppresses these cross-polar systematics is discussed in detail. The estimates and formalism provided in this work offer key tools in the design consideration of the instruments using the multimoded polarimeters. PMID- 25121446 TI - On calculating metamer sets for spectrally tunable LED illuminators. AB - Solid state lighting is becoming a popular light source for color vision experiments. One of the advantages of light emitting diodes (LEDs) is the possibility to shape the target light spectrum according to the experimenter's needs. In this paper, we present a method for creating metameric lights with an LED-based spectrally tunable illuminator. The equipment we use consists of six Gamma Scientific RS-5B lamps, each containing nine different LEDs and a 1 m integrating sphere. We provide a method for describing the (almost) entire set of illuminant metamers. It will be shown that the main difficulty in describing this set arises as the result of the intensity dependent peak-wavelength shift, which is manifested by the majority of the LEDs used by the illuminators of this type. We define the normalized metamer set describing all illuminator spectra that colorimetrically match a given chromaticity. Finally, we describe a method for choosing the smoothest or least smooth metamer from the entire set. PMID- 25121447 TI - Bloch modes at the surface of a photonic crystal interacting with a waveguide. AB - We theoretically studied the influence of an infinite set of waveguides on the evanescent field of Bloch waves at the surface of a one-dimensional photonic crystal (PC) excited by a TE Gaussian beam undergoing total internal reflection. The set of waveguides is regarded as a periodic inhomogeneous medium with period a. Numerical results are presented for the case in which a is greater than lambda, which is the wavelength used to excite the surface mode. When the waveguide tip is very close to the surface of the PC, a fraction of the surface wave is reflected by the tip, producing an interference pattern that can be observed in the near field. In this case, the system simulates scanning tunneling optical microscopy in 2D geometry, and an image of the field distribution of the surface mode is obtained by quantifying the flux energy throughout the waveguide. PMID- 25121448 TI - Maxwell-Gaussian beams with cylindrical polarization. AB - It is common practice to work in the approximation that beam-like radiation fields are polarized transverse to the propagation axis. However, even in the paraxial approximation, this fails to correctly describe beam polarization and propagation characteristics. We present here the paraxial Maxwell's equations for beams having cylindrical polarization, which describe the full vector structure of these beams in the paraxial regime. The effect that these relations have on the polarization and propagation of cylindrically polarized Laguerre-Gauss and Bessel-Gauss beams is subsequently explored. PMID- 25121450 TI - One-dimensional finite-elements method for the analysis of whispering gallery microresonators. AB - By taking advantage of axial symmetry of the planar whispering gallery microresonators, the three-dimensional (3D) problem of the resonator is reduced to a two-dimensional (2D) one; thus, only the cross section of the resonator needs to be analyzed. Then, the proposed formulation, which works based on a combination of the finite-elements method (FEM) and Fourier expansion of the fields, can be applied to the 2D problem. First, the axial field variation is expressed in terms of a Fourier series. Then, a FEM method is applied to the radial field variation. This formulation yields an eigenvalue problem with sparse matrices and can be solved using a well-known numerical technique. This method takes into account both the radiation loss and the dielectric loss; hence, it works efficiently either for high number or low number modes. Efficiency of the method was investigated by comparison of the results with those of commercial software. PMID- 25121449 TI - Zernike expansion of derivatives and Laplacians of the Zernike circle polynomials. AB - The partial derivatives and Laplacians of the Zernike circle polynomials occur in various places in the literature on computational optics. In a number of cases, the expansion of these derivatives and Laplacians in the circle polynomials are required. For the first-order partial derivatives, analytic results are scattered in the literature. Results start as early as 1942 in Nijboer's thesis and continue until present day, with some emphasis on recursive computation schemes. A brief historic account of these results is given in the present paper. By choosing the unnormalized version of the circle polynomials, with exponential rather than trigonometric azimuthal dependence, and by a proper combination of the two partial derivatives, a concise form of the expressions emerges. This form is appropriate for the formulation and solution of a model wavefront sensing problem of reconstructing a wavefront on the level of its expansion coefficients from (measurements of the expansion coefficients of) the partial derivatives. It turns out that the least-squares estimation problem arising here decouples per azimuthal order m, and per m the generalized inverse solution assumes a concise analytic form so that singular value decompositions are avoided. The preferred version of the circle polynomials, with proper combination of the partial derivatives, also leads to a concise analytic result for the Zernike expansion of the Laplacian of the circle polynomials. From these expansions, the properties of the Laplacian as a mapping from the space of circle polynomials of maximal degree N, as required in the study of the Neumann problem associated with the transport of-intensity equation, can be read off within a single glance. Furthermore, the inverse of the Laplacian on this space is shown to have a concise analytic form. PMID- 25121451 TI - Majorization and measures of classical polarization in three dimensions. AB - There has been much discussion in the literature about rival measures of classical polarization in three dimensions. We gather and compare the various proposed measures of polarization, creating a geometric representation of the polarization state space in the process. We use majorization, previously used in quantum information, as a criterion to establish a partial ordering on the polarization state space. Using this criterion and other considerations, the most useful polarization measure in three dimensions is found to be one dependent on the Bloch vector decomposition of the polarization matrix. PMID- 25121452 TI - Partial polarization of optical beams and near fields probed with a nanoscatterer. AB - We consider theoretically the detection of the spectral polarization characteristics of random, partially polarized optical beams and near fields by probing them with a dipolar nanoparticle. We show that measuring the polarization state of the scattered far field with a conventional waveplate-polarizer setup, possibly in several directions, results in the full 3*3 polarization matrix at the probe site. This allows us to deduce the distributions of the degree of polarization of the field and the Stokes parameters of the polarized part of the field with a resolution limited by the probe size. Regarding random near fields we show that, in analogy with a known result on beam fields, a degree of polarization of three-component light fields put forward in recent literature can in some cases be interpreted as a ratio of the intensity in the polarized part of the light to that of the total field. We demonstrate the technique by considering the probing of a Gaussian-Schell model beam and a thermally excited near field. The method extends the current scanning-probe techniques to the detection of partial polarization of random light fields and can find applications in nanophotonics and polarization optics. PMID- 25121453 TI - Silhouette estimation. AB - Silhouettes arise in a variety of imaging scenarios. Pristine silhouettes are often degraded via blurring, detector sampling, and detector noise. We present a maximum a posteriori estimator for the restoration of parameterized facial silhouettes. Extreme dealiasing and dramatic superresolution, well beyond the diffraction limit, are demonstrated through the use of strong prior knowledge. PMID- 25121454 TI - Accuracy of sun localization in the second step of sky-polarimetric Viking navigation for north determination: a planetarium experiment. AB - It is a widely discussed hypothesis that Viking seafarers might have been able to locate the position of the occluded sun by means of dichroic or birefringent crystals, the mysterious sunstones, with which they could analyze skylight polarization. Although the atmospheric optical prerequisites and certain aspects of the efficiency of this sky-polarimetric Viking navigation have been investigated, the accuracy of the main steps of this method has not been quantitatively examined. To fill in this gap, we present here the results of a planetarium experiment in which we measured the azimuth and elevation errors of localization of the invisible sun. In the planetarium sun localization was performed in two selected celestial points on the basis of the alignments of two small sections of two celestial great circles passing through the sun. In the second step of sky-polarimetric Viking navigation the navigator needed to determine the intersection of two such celestial circles. We found that the position of the sun (solar elevation theta(S), solar azimuth phi(S)) was estimated with an average error of +0.6 degrees <=Deltatheta<=+8.8 degrees and 3.9 degrees <=Deltaphi<=+2.0 degrees . We also calculated the compass direction error when the estimated sun position is used for orienting with a Viking sun compass. The northern direction (omega(North)) was determined with an error of 3.34 degrees <=Deltaomega(North)<=+6.29 degrees . The inaccuracy of the second step of this navigation method was high (Deltaomega(North)=-16.3 degrees ) when the solar elevation was 5 degrees <=theta(S)<=25 degrees , and the two selected celestial points were far from the sun (at angular distances 95 degrees <=gamma(1), gamma(2)<=115 degrees ) and each other (125 degrees <=delta<=145 degrees ). Considering only this second step, the sky-polarimetric navigation could be more accurate in the mid-summer period (June and July), when in the daytime the sun is high above the horizon for long periods. In the spring (and autumn) equinoctial period, alternative methods (using a twilight board, for example) might be more appropriate. Since Viking navigators surely also committed further errors in the first and third steps, the orientation errors presented here underestimate the net error of the whole sky-polarimetric navigation. PMID- 25121455 TI - Nonparaxial propagation and focusing properties of azimuthal-variant vector fields diffracted by an annular aperture. AB - Based on the vectorial Rayleigh-Sommerfeld integrals, the analytical expressions for azimuthal-variant vector fields diffracted by an annular aperture are presented. This helps us to investigate the propagation behaviors and the focusing properties of apertured azimuthal-variant vector fields under nonparaxial and paraxial approximations. The diffraction by a circular aperture, a circular disk, or propagation in free space can be treated as special cases of this general result. Simulation results show that the transverse intensity, longitudinal intensity, and far-field divergence angle of nonparaxially apertured azimuthal-variant vector fields depend strongly on the azimuthal index, the outer truncation parameter and the inner truncation parameter of the annular aperture, as well as the ratio of the waist width to the wavelength. Moreover, the multiple ring-structured intensity pattern of the focused azimuthal-variant vector field, which originates from the diffraction effect caused by an annular aperture, is experimentally demonstrated. PMID- 25121456 TI - Spatial-temporal-covariance-based modeling, analysis, and simulation of aero optics wavefront aberrations. AB - We introduce a framework for modeling, analysis, and simulation of aero-optics wavefront aberrations that is based on spatial-temporal covariance matrices extracted from wavefront sensor measurements. Within this framework, we present a quasi-homogeneous structure function to analyze nonhomogeneous, mildly anisotropic spatial random processes, and we use this structure function to show that phase aberrations arising in aero-optics are, for an important range of operating parameters, locally Kolmogorov. This strongly suggests that the d5/3 power law for adaptive optics (AO) deformable mirror fitting error, where d denotes actuator separation, holds for certain important aero-optics scenarios. This framework also allows us to compute bounds on AO servo lag error and predictive control error. In addition, it provides us with the means to accurately simulate AO systems for the mitigation of aero-effects, and it may provide insight into underlying physical processes associated with turbulent flow. The techniques introduced here are demonstrated using data obtained from the Airborne Aero-Optics Laboratory. PMID- 25121457 TI - Object-color-signal prediction using wraparound Gaussian metamers. AB - Alexander Logvinenko introduced an object-color atlas based on idealized reflectances called rectangular metamers in 2009. For a given color signal, the atlas specifies a unique reflectance that is metameric to it under the given illuminant. The atlas is complete and illuminant invariant, but not possible to implement in practice. He later introduced a parametric representation of the object-color atlas based on smoother "wraparound Gaussian" functions. In this paper, these wraparound Gaussians are used in predicting illuminant-induced color signal changes. The method proposed in this paper is based on computationally "relighting" that reflectance to determine what its color signal would be under any other illuminant. Since that reflectance is in the metamer set the prediction is also physically realizable, which cannot be guaranteed for predictions obtained via von Kries scaling. Testing on Munsell spectra and a multispectral image shows that the proposed method outperforms the predictions of both those based on von Kries scaling and those based on the Bradford transform. PMID- 25121458 TI - Modulation transfer function of a triangular pixel array detector. AB - The modulation transfer function (MTF) is the main parameter that is used to evaluate image quality in electro-optical systems. Detector sampling MTF in most electro-optical systems determines the cutoff frequency of the system. The MTF of the detector depends on its pixel shape. In this work, we calculated the MTF of a detector with an equilateral triangular pixel shape. Some new results were found in deriving the MTF for the equilateral triangular pixel shape. PMID- 25121459 TI - Validity of the Dysexecutive Questionnaire (DEX). Ratings by patients with brain injury and their therapists. AB - OBJECTIVE: This study investigated the validity of the DEX-Questionnaire (both completed by patients, DEX-Self and by therapists, DEX-TH), included in the Behavioural Assessment of the Dysexecutive Syndrome (BADS), at identifying differences in the severity of dysexecutive symptoms according to lesion location. It also examined the strength of associations of the DEX-Self and the DEX-TH reports with the sub-tests of the BADS as well as two other real-life executive tasks, the Everyday Description Task and the Twenty Question Test. METHODS: This study compared 30 patients with anterior lesions (AL) to 22 patients with posterior lesions (PL). Twenty-nine healthy participants and their relatives were included as controls. RESULTS: Significant group differences were found only on the DEX-TH, but not on the DEX-Self, indicating poor insight in patients with AL. The DEX-TH were revealed accurate in detecting more severe dysexecutive symptoms in the AL group. Furthermore, only the DEX-TH reportings were significantly correlated with the above executive tests. Multiple regression analysis showed that the Modified Six Elements Test, a sub-test of the BADS, predicted DEX-TH as accurately as the total BADS. CONCLUSION: The DEX-TH reportings and the MSET can provide valuable information about the severity of daily executive dysfunctioning, with implications for cognitive rehabilitation. PMID- 25121460 TI - Mixtures of lecithin and bile salt can form highly viscous wormlike micellar solutions in water. AB - The self-assembly of biological surfactants in water is an important topic for study because of its relevance to physiological processes. Two common types of biosurfactants are lecithin (phosphatidylcholine) and bile salts, which are both present in bile and involved in digestion. Previous studies on lecithin-bile salt mixtures have reported the formation of short, rodlike micelles. Here, we show that lecithin-bile salt micelles can be further induced to grow into long, flexible wormlike structures. The formation of long worms and their resultant entanglement into transient networks is reflected in the rheology: the fluids become viscoelastic and exhibit Maxwellian behavior, and their zero-shear viscosity can be up to a 1000-fold higher than that of water. The presence of worms is further confirmed by data from small-angle neutron and X-ray scattering and from cryo-transmission electron microscopy (cryo-TEM). We find that micellar growth peaks at a specific molar ratio (near equimolar) of bile salt:lecithin, which suggests a strong binding interaction between the two species. In addition, micellar growth also requires a sufficient concentration of background electrolyte such as NaCl or sodium citrate that serves to screen the electrostatic repulsion of the amphiphiles and to "salt out" the amphiphiles. We postulate a mechanism based on changes in the molecular geometry caused by bile salts and electrolytes to explain the micellar growth. PMID- 25121461 TI - Isotopic fractionation by a fungal P450 nitric oxide reductase during the production of N2O. AB - Nitrous oxide (N2O) is a potent greenhouse gas with a 100-year global warming potential approximately 300 times that of CO2. Because microbes account for over 75% of the N2O released in the U.S., understanding the biochemical processes by which N2O is produced is critical to our efforts to mitigate climate change. In the current study, we used gas chromatography-isotope ratio mass spectrometry (GC IRMS) to measure the delta(15)N, delta(18)O, delta(15)N(alpha), and delta(15)N(beta) of N2O generated by purified fungal nitric oxide reductase (P450nor) from Histoplasma capsulatum. The isotope values were used to calculate site preference (SP) values (difference in delta(15)N between the central (alpha) and terminal (beta) N atoms in N2O), enrichment factors (epsilon), and kinetic isotope effects (KIEs). Both oxygen and N(alpha) displayed normal isotope effects during enzymatic NO reduction with epsilon values of -25.70/00 (KIE = 1.0264) and -12.60/00 (KIE = 1.0127), respectively. However, bulk nitrogen (average delta(15)N of N(alpha) and N(beta)) and N(beta) exhibited inverse isotope effects with epsilon values of 14.00/00 (KIE = 0.9862) and 36.10/00 (KIE = 0.9651), respectively. The observed inverse isotope effect in delta(15)N(beta) is consistent with reversible binding of the first NO in the P450nor reaction mechanism. In contrast to the constant SP observed during NO reduction in microbial cultures, the site preference measured for purified H. capsulatum P450nor was not constant, increasing from ~ 150/00 to ~ 290/00 during the course of the reaction. This indicates that SP for microbial cultures can vary depending on the growth conditions, which may complicate source tracing during microbial denitrification. PMID- 25121462 TI - Vitamin D deficiency and infertility: insights from in vitro fertilization cycles. AB - CONTEXT: Vitamin D deficiency has been proven to affect fertility in mammals, but data in human is less convincing. In particular, data on in vitro fertilization (IVF), an attractive model to draw information on this topic, are sparse and conflicting. OBJECTIVE: Our objective was to investigate IVF outcome in women with deficient 25-hydroxy-vitamin D [25(OH)D] serum levels (<20 ng/mL). DESIGN AND SETTING: This prospective cross-sectional study was conducted at the infertility unit of an academic setting. PATIENTS: The main inclusion criteria were as follows: (1) indication to IVF, (2) age 18-42 years, (3) BMI 18-25 kg/m(2), (4) adequate ovarian reserve according to Bologna criteria. Eligible women provided a serum sample for 25(OH)D measurement at the time of cycle preparation. Subjects were subsequently excluded if the cycle was cancelled or if the attempt was excessively delayed. INTERVENTION: Quantitative detection of serum 25(OH)D. MAIN OUTCOME MEASURE: Clinical pregnancy rate. RESULTS: The number of recruited women with serum 25(OH)D <20 ng/mL and >= 20 ng/mL was 154 and 181, respectively. The clinical pregnancy rates were 20% (30/154) and 31% (56/181), respectively (P = .02); the adjusted odds ratio for clinical pregnancy in women with vitamin D >= 20 ng/mL was 2.15 (95% CI: 1.23-3.77). Subgroup analyses showed that the group of women with the highest serum levels (>30 ng/mL) had the highest chances of pregnancy. CONCLUSIONS: Vitamin D is an emerging factor influencing female fertility and IVF outcome. Additional studies are pressingly needed to confirm a causal relationship and to investigate the potential therapeutic benefits of vitamin D supplementation. PMID- 25121463 TI - 131I-noriodocholesterol uptake by testicular adrenal rest tumors in a patient with classical 21-hydroxylase deficiency. PMID- 25121465 TI - Copper clusters as novel fluorescent probes for the detection and photocatalytic elimination of lead ions. AB - A new homogeneous assay for a fast, selective and sensitive detection and elimination of lead ions has been developed using copper clusters as novel fluorescent probes in aqueous solutions. At the same time, their elimination is achieved using the efficient photocatalytic activity of such clusters. Both effects are explained in terms of an efficient electron transfer due to the LUMO energy of the cluster overlapping with the ion redox potential. The mechanism, which allows the explanation of previously reported results for different types of metal clusters, is further confirmed using smaller and larger Cu clusters displaying non-selective and non-quenching luminescence in the presence of different cations. PMID- 25121471 TI - It's a small World. PMID- 25121464 TI - Urinary phthalate metabolites are associated with decreased serum testosterone in men, women, and children from NHANES 2011-2012. AB - CONTEXT: There is evidence of declining trends in T levels among men in recent decades, as well as trends in related conditions at multiple life stages and in both sexes. There is also animal and limited human evidence that exposure to phthalates, chemicals found in plastics and personal care products, is associated with reduced androgen levels and associated disorders. OBJECTIVE: To explore relationships between urinary concentrations of 13 phthalate metabolites and serum total T levels among men, women, and children when adjusting for important confounders and stratifying by sex and age (6-12, 12-20, 20-40, 40-60, and 60-80 y). DESIGN: A cross-sectional study. SETTING: US National Health and Nutrition Examination Survey, 2011-2012. PATIENTS OR OTHER PARTICIPANTS: US general population. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum total T measured by isotope dilution-liquid chromatography-tandem mass spectrometry. RESULTS: Multiple phthalates were associated with significantly reduced T in both sexes and in differing age groups. In females, the strongest and most consistent inverse relationships were found among women ages 40-60 years. In boys 6-12 years old, an interquartile range increase in metabolites of di-2-ethylhexyl phthalate was associated with a 29% (95% confidence interval, 6, 47) reduction in T. In adult men, the only significant or suggestive inverse associations between phthalates (metabolites of di-2-ethylhexyl phthalate and dibutyl phthalate) and T were observed among men ages 40-60 years. CONCLUSIONS: Because T plays an important role in all life stages for both sexes, future efforts should focus on better defining these relationships and their broader impacts. PMID- 25121472 TI - Fine structures of self-assembled beta-cyclodextrin/Pluronic in dilute and dense systems: a small angle X-ray scattering study. AB - The evolution of the fine structures of self-assembled polypseudorotaxane (PPR) in Pluronic (PL F108) solutions containing dilute to dense beta-cyclodextrin (beta-CD) was illustrated for the first time by small angle X-ray scattering (SAXS). Dense beta-CD (~19 w/v%) was found feasible to be dispersed in 24% citric acid solution. 5% of PL F108 formed cylindrical micelles of 1 nm in radius and 8 nm in length in the presence of 24% citric acid through the dehydration of citric acid and citrate. PPR was formed through host-guest interaction between PL F108 and beta-CD. In dilute beta-CD system (1%), the single chains of PPR with separated beta-CD stacks on PL F108 were formed. The numbers of beta-CD in each stack increased from 1 to 4 on increasing beta-CD concentration to 9%. In a dense beta-CD system, PPR condensed to correlated structures majorly composed of two unit blocks through the hydrogen bonds between PPRs. Two distinguishable correlated domains with correlation lengths of 50 nm (marked alpha-phase) and 46 nm (marked beta-phase) along the chains, but without fine periodic structure within each individual domain, were identified in the 10% beta-CD solution. Periodic stacking of beta-CD in the domains developed in the 12% solution. As beta-CD concentration increased from 12 to 19%, the correlated heights of alpha and beta phases reduced from 41 and 32 nm to 30 and 10 nm, respectively. There were 48 beta-CDs that stabilized on each PL F108 chain in the 19% beta-CD system, which is in good agreement with stoichiometry. PMID- 25121473 TI - Graft and patient survival outcomes of a third kidney transplant. AB - BACKGROUND: The waiting time for deceased donor renal transplantation in the United States continues to grow. Retransplant candidates make up a small but growing percentage of the overall transplant waiting list and raise questions about the stewardship of scarce resources. The utility of renal transplantation among individuals with two prior renal transplants is not described in the literature, and we thus sought to determine the survival benefit associated with a third kidney transplant (3KT). METHODS: Multivariable Cox regression models were created to determine characteristics associated with 3KT outcomes and the survival benefit of 3KT among recipients wait listed and transplanted within the United States between 1995 and 2009. RESULTS: A total of 4,334 patients were waitlisted for a 3KT and 2,492 patients received a 3KT. In a multivariate analysis, 3KT demonstrated an overall patient survival benefit compared to the waitlist (hazards ratio, 0.379; 95% confidence interval, 0.302-0.475; P<0.001) for those awaiting their first, second, or third kidney transplants, although an inferior graft outcome compared to first kidney transplants. The time to survival benefit did not accrue until 8 months after transplantation. In addition, we found that the duration of second graft survival was predictive of third graft survival, such that second graft survival beyond 5 years is associated with superior 3KT graft survival. Second graft loss in 30 days or less was not associated with inferior 3KT graft survival. CONCLUSION: A 3KT achieves a survival benefit over remaining on the waitlist, although is associated with inferior graft outcomes compared to first kidney transplants. Graft survival of the second transplant beyond 5 years is associated with superior 3KT graft survival. PMID- 25121475 TI - Eculizumab and splenectomy as salvage therapy for severe antibody-mediated rejection after HLA-incompatible kidney transplantation. AB - BACKGROUND: Incompatible live donor kidney transplantation is associated with an increased rate of antibody-mediated rejection (AMR) and subsequent transplant glomerulopathy. For patients with severe, oliguric AMR, graft loss is inevitable without timely intervention. METHODS: We reviewed our experience rescuing kidney allografts with this severe AMR phenotype by using splenectomy alone (n=14), eculizumab alone (n=5), or splenectomy plus eculizumab (n=5), in addition to plasmapheresis. RESULTS: The study population was 267 consecutive patients with donor-specific antibody undergoing desensitization. In the first 3 weeks after transplantation (median=6 days), 24 patients developed sudden onset oliguria and rapidly rising serum creatinine with marked rebound of donor-specific antibody, and a biopsy that showed features of AMR. At a median follow-up of 533 days, 4 of 14 splenectomy-alone patients experienced graft loss (median=320 days), compared to four of five eculizumab-alone patients with graft failure (median=95 days). No patients treated with splenectomy plus eculizumab experienced graft loss. There was more chronic glomerulopathy in the splenectomy-alone and eculizumab-alone groups at 1 year, whereas splenectomy plus eculizumab patients had almost no transplant glomerulopathy. CONCLUSION: These data suggest that for patients manifesting early severe AMR, splenectomy plus eculizumab may provide an effective intervention for rescuing and preserving allograft function. PMID- 25121474 TI - Indicators of treatment responsiveness to rituximab and plasmapheresis in antibody-mediated rejection after kidney transplantation. AB - BACKGROUND: Treatment of patients with antibody-mediated rejection (AMR) after kidney transplantation by rituximab and plasmapheresis is ambiguous. Because of its unknown efficiency and serious side effects, biomarkers, which are predictive for responsiveness to this treatment in AMR patients, are required. METHODS: Twenty renal transplant patients were included in this retrospective study. Selection was based on Renal Index Biopsies, classified according to Banff within 3 months before treatment. Patients were categorized into responders (R) and nonresponders (NR) depending on whether they returned to dialysis within 6 months after initiation of rituximab treatment. Clinical, histopathologic (Banff classification) and serologic parameters were compared between both groups by t test, Mann-Whitney U test, or likelihood ratio chi-square test. RESULTS: In comparisons between the groups, the R group showed a 1.5-fold higher level of estimated glomerular filtration rate and a fourfold lower level of proteinuria. By contrast, there were no differences in the histologic scores for chronic transplant lesions between the groups. The t and i scores were higher in NRs, whereas Banff-C4d scores of peritubular capillaries were increased in the Rs. Transplant biopsies in the Rs exhibited more CD138+ cell infiltrates. Serologic determination of human leukocyte antigen antibodies showed higher positivity for human leukocyte antigen class II donor-specific antibodies in the R group. No significant differences in other clinical criteria were found. CONCLUSION: Increased proteinuria, decreased graft function, and a higher grade of tubulitis and inflammation in AMR are negative predictors for responsiveness to rituximab therapy. Rituximab therapy therefore should be initiated in an early phase of AMR. PMID- 25121476 TI - Outcomes after pregnancy in living lobar lung transplantation. AB - Pregnancy after lung transplantation has been described, but pregnancy after living donor lobar lung transplantation (LDLT) has not been reported. The aim of this study was to evaluate outcomes after pregnancy with LDLT and discuss current recommendations regarding pregnancy and lung transplantation. A total of four LDLT patients and five pregnancies were identified, all from our institution. No patient has developed worsening pulmonary function or acute or chronic rejection. The complications of pulmonary hypertension and rejection may be overestimated in this population, and recommendations for preventive sterilization at transplantation or abortion at the time of conception are likely unwarranted and unnecessary. PMID- 25121477 TI - Contact tracing investigation after professional exposure to tuberculosis in a Swiss hospital using both tuberculin skin test and IGRA. AB - SETTING: A 950 bed teaching hospital in Switzerland. AIM: To describe the result of a contact investigation among health care workers (HCW) and patients after exposure to a physician with smear-positive pulmonary tuberculosis in a hospital setting using standard tuberculin skin tests (TST) and Interferon-gamma release assay (IGRA). METHOD: HCW with a negative or unknown TST at hiring had a TST two weeks after the last contact with the index case (T0), repeated six weeks later if negative (T6). All exposed HCW had a T-SPOT.TB at T0 and T6. Exposed patients had a TST six weeks after the last contact, and a T-SPOT.TB if the TST was positive. RESULTS: Among 101 HCW, 17/73 (22%) had a positive TST at T0. TST was repeated in 50 at T6 and converted from negative to positive in eight (16%). Twelve HCW had a positive T-SPOT.TB at T0 and ten converted from negative to positive at T6. Seven HCW with a positive T-SPOT.TB reverted to negative at T6 or at later controls, most of them with test values close to the cut-off. Among 27 exposed patients tested at six weeks, ten had a positive TST, five of them confirmed by a positive T-SPOT.TB. CONCLUSIONS: HCW tested twice after exposure to a case of smear-positive pulmonary TB demonstrated a possible conversion in 10% with T-SPOT and 16% with TST. Some T-SPOT.TB reverted from positive to negative during the follow-up, mostly tests with a value close to the cut-off. Due to the variability of the test results, it seems advisable to repeat the test with values close to the cut-off before diagnosing the presence of a tuberculous infection. PMID- 25121478 TI - Review of recent developments in stimulated emission depletion microscopy: applications on cell imaging. AB - Stimulated emission depletion (STED) microscopy is one type of far-field optical technique demonstrated to provide subdiffraction resolution. STED microscopy utilizes a donut-shaped depletion beam to limit the probe volume to be much smaller than a diffraction-limited spot. Resolutions as small as a few tens of nanometers laterally are reported for cell analysis. The different versions of STED microscopes are described and contrasted in terms of their applicability for biological imaging. Finally, we suggest likely avenues for improving the performance and increasing the utility of STED microscopy. PMID- 25121479 TI - Performance assessment of time-domain optical brain imagers, part 1: basic instrumental performance protocol. AB - Performance assessment of instruments devised for clinical applications is of key importance for validation and quality assurance. Two new protocols were developed and applied to facilitate the design and optimization of instruments for time domain optical brain imaging within the European project nEUROPt. Here, we present the "Basic Instrumental Performance" protocol for direct measurement of relevant characteristics. Two tests are discussed in detail. First, the responsivity of the detection system is a measure of the overall efficiency to detect light emerging from tissue. For the related test, dedicated solid slab phantoms were developed and quantitatively spectrally characterized to provide sources of known radiance with nearly Lambertian angular characteristics. The responsivity of four time-domain optical brain imagers was found to be of the order of 0.1 m2 sr. The relevance of the responsivity measure is demonstrated by simulations of diffuse reflectance as a function of source-detector separation and optical properties. Second, the temporal instrument response function (IRF) is a critically important factor in determining the performance of time-domain systems. Measurements of the IRF for various instruments were combined with simulations to illustrate the impact of the width and shape of the IRF on contrast for a deep absorption change mimicking brain activation. PMID- 25121481 TI - Polarized Raman spectroscopic investigations on hemoglobin ordering in red blood cells. AB - We have investigated the dependence of the Raman spectrum of an optically trapped red blood cell (RBC) on the orientation of the cell, relative to the polarization direction of the Raman excitation beam. The Raman scattered light polarized parallel to the polarization direction of the excitation beam was observed to depend upon the orientation of the cell. In particular, the heme bands at ~754 cm 1 and in the 1500 to 1700 cm-1 region were observed to become maximum when the cells' equatorial plane was parallel to the excitation beam polarization direction and minimum when the cells' plane was normal to the polarization direction. In contrast, no significant orientational dependence was seen in the Raman scattered light polarized orthogonal to the polarization direction of the excitation beam. Theoretical simulations carried out to investigate these observations suggest that inside the RBCs, the hemoglobin molecules must be present in an ordered arrangement, such that heme-porphyrin planes become preferentially orientated parallel to the RBCs' equatorial plane. PMID- 25121480 TI - Performance assessment of time-domain optical brain imagers, part 2: nEUROPt protocol. AB - The nEUROPt protocol is one of two new protocols developed within the European project nEUROPt to characterize the performances of time-domain systems for optical imaging of the brain. It was applied in joint measurement campaigns to compare the various instruments and to assess the impact of technical improvements. This protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain. It was implemented with two types of inhomogeneous liquid phantoms based on Intralipid and India ink with well-defined optical properties. First, small black inclusions were used to mimic localized changes of the absorption coefficient. The position of the inclusions was varied in depth and lateral direction to investigate contrast and spatial resolution. Second, two-layered liquid phantoms with variable absorption coefficients were employed to study the quantification of layer-wide changes and, in particular, to determine depth selectivity, i.e., the ratio of sensitivities for deep and superficial absorption changes. We introduce the tests of the nEUROPt protocol and present examples of results obtained with different instruments and methods of data analysis. This protocol could be a useful step toward performance tests for future standards in diffuse optical imaging. PMID- 25121482 TI - Distinct APC subtypes drive spatially segregated CD4+ and CD8+ T-cell effector activity during skin infection with HSV-1. AB - Efficient infection control requires potent T-cell responses at sites of pathogen replication. However, the regulation of T-cell effector function in situ remains poorly understood. Here, we show key differences in the regulation of effector activity between CD4+ and CD8+ T-cells during skin infection with HSV-1. IFN gamma-producing CD4+ T cells disseminated widely throughout the skin and draining lymph nodes (LN), clearly exceeding the epithelial distribution of infectious virus. By contrast, IFN-gamma-producing CD8+ T cells were only found within the infected epidermal layer of the skin and associated hair follicles. Mechanistically, while various subsets of lymphoid- and skin-derived dendritic cells (DC) elicited IFN-gamma production by CD4+ T cells, CD8+ T cells responded exclusively to infected epidermal cells directly presenting viral antigen. Notably, uninfected cross-presenting DCs from both skin and LNs failed to trigger IFN-gamma production by CD8+ T-cells. Thus, we describe a previously unappreciated complexity in the regulation of CD4+ and CD8+ T-cell effector activity that is subset-specific, microanatomically distinct and involves largely non-overlapping types of antigen-presenting cells (APC). PMID- 25121483 TI - Serotonin 5-HT3 receptor-mediated vomiting occurs via the activation of Ca2+/CaMKII-dependent ERK1/2 signaling in the least shrew (Cryptotis parva). AB - Stimulation of 5-HT3 receptors (5-HT3Rs) by 2-methylserotonin (2-Me-5-HT), a selective 5-HT3 receptor agonist, can induce vomiting. However, downstream signaling pathways for the induced emesis remain unknown. The 5-HT3R channel has high permeability to extracellular calcium (Ca(2+)) and upon stimulation allows increased Ca(2+) influx. We examined the contribution of Ca(2+)/calmodulin dependent protein kinase IIalpha (Ca(2+)/CaMKIIalpha), interaction of 5-HT3R with calmodulin, and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling to 2 Me-5-HT-induced emesis in the least shrew. Using fluo-4 AM dye, we found that 2 Me-5-HT augments intracellular Ca(2+) levels in brainstem slices and that the selective 5-HT3R antagonist palonosetron, can abolish the induced Ca(2+) signaling. Pre-treatment of shrews with either: i) amlodipine, an antagonist of L type Ca(2+) channels present on the cell membrane; ii) dantrolene, an inhibitor of ryanodine receptors (RyRs) Ca2+-release channels located on the endoplasmic reticulum (ER); iii) a combination of their less-effective doses; or iv) inhibitors of CaMKII (KN93) and ERK1/2 (PD98059); dose-dependently suppressed emesis caused by 2-Me-5-HT. Administration of 2-Me-5-HT also significantly: i) enhanced the interaction of 5-HT3R with calmodulin in the brainstem as revealed by immunoprecipitation, as well as their colocalization in the area postrema (brainstem) and small intestine by immunohistochemistry; and ii) activated CaMKIIalpha in brainstem and in isolated enterochromaffin cells of the small intestine as shown by Western blot and immunocytochemistry. These effects were suppressed by palonosetron. 2-Me-5-HT also activated ERK1/2 in brainstem, which was abrogated by palonosetron, KN93, PD98059, amlodipine, dantrolene, or a combination of amlodipine plus dantrolene. However, blockade of ER inositol-1, 4, 5-triphosphate receptors by 2-APB, had no significant effect on the discussed behavioral and biochemical parameters. This study demonstrates that Ca(2+) mobilization via extracellular Ca(2+) influx through 5-HT3Rs/L-type Ca(2+) channels, and intracellular Ca(2+) release via RyRs on ER, initiate Ca(2+) dependent sequential activation of CaMKIIalpha and ERK1/2, which contribute to the 5-HT3R-mediated, 2-Me-5-HT-evoked emesis. PMID- 25121485 TI - Compromised dynamic cerebral autoregulation in patients with a right-to-left shunt: a potential mechanism of migraine and cryptogenic stroke. AB - BACKGROUND AND PURPOSE: The relationship between right-to-left shunts (RLS) and migraine and cryptogenic stroke is not well understood. In this study, we investigated whether RLS are associated with impairment of dynamic cerebral autoregulation (dCA), which may play a role in migraine and cryptogenic stroke. METHODS: Sixty-six migraineurs were enrolled in the study, including 36 non-RLS patients and 30 RLS patients. Non-invasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously from each patient by using transcranial Doppler and servo-controlled plethysmograph, respectively. Transfer function analysis was applied to derive autoregulatory parameters of gain, phase difference (PD), and autoregulation index. RESULTS: The PD in migraineurs with RLS was 50.6 +/- 22.9 degrees, which was significantly lower than that observed in the non-RLS group (67.2 +/- 18.2 degrees, P<0.001). The PD in the large RLS group (45.4 +/- 22.6 degrees) was significantly lower than that of the small RLS group (64.9 +/- 17.1 degrees, P<0.01) and non-RLS group (P<0.001); however, the PD in the small RLS group was similar to that of the non-RLS group. The PD in the permanent group (48.8 +/- 19.9 degrees) was similar to that of the latent group (52.6 +/- 26.1 degrees), and both were significantly lower than that of the non-RLS group (P<0.05). The autoregulation index results were similar to the PD findings. CONCLUSIONS: dCA is impaired in migraineurs with large RLS, and this may represent a potential mechanism linking RLS, migraine, and cryptogenic stroke. PMID- 25121484 TI - The protective role of symmetric stem cell division on the accumulation of heritable damage. AB - Stem cell divisions are either asymmetric-in which one daughter cell remains a stem cell and one does not-or symmetric, in which both daughter cells adopt the same fate, either stem or non-stem. Recent studies show that in many tissues operating under homeostatic conditions stem cell division patterns are strongly biased toward the symmetric outcome, raising the question of whether symmetry confers some benefit. Here, we show that symmetry, via extinction of damaged stem cell clones, reduces the lifetime risk of accumulating phenotypically silent heritable damage (mutations or aberrant epigenetic changes) in individual stem cells. This effect is greatest in rapidly cycling tissues subject to accelerating rates of damage accumulation over time, a scenario that describes the progression of many cancers. A decrease in the rate of cellular damage accumulation may be an important factor favoring symmetric patterns of stem cell division. PMID- 25121486 TI - Altered resting-state FMRI signals in acute stroke patients with ischemic penumbra. AB - BACKGROUND: Identifying the ischemic penumbra in acute stroke subjects is important for the clinical decision making process. The aim of this study was to use resting-state functional magnetic resonance singal (fMRI) to investigate the change in the amplitude of low-frequency fluctuations (ALFF) of these subjects in three different subsections of acute stroke regions: the infarct core tissue, the penumbra tissue, and the normal brain tissue. Another aim of this study was to test the feasilbility of consistently detecting the penumbra region of the brain through ALFF analysis. METHODS: Sixteen subjects with first-ever acute ischemic stroke were scanned within 27 hours of the onset of stroke using magnetic resonance imaging. The core of infarct regions and penumbra regions were determined by diffusion and perfusion-weighted imaging respectively. The ALFF were measured from resting-state blood oxygen level dependent (BOLD) fMRI scans. The averaged relative ALFF value of each regions were correlated with the time after the onset of stroke. RESULTS: Relative ALFF values were significantly different in the infarct core tissue, penumbra tissue and normal brain tissue. The locations of lesions in the ALFF maps did not match perfectly with diffusion and perfusion-weighted imagings; however, these maps provide a contrast that can be used to differentiate between penumbra brain tissue and normal brain tissue. Significant correlations between time after stroke onset and the relative ALFF values were present in the penumbra tissue but not in the infarct core and normal brain tissue. CONCLUSION: Preliminary results from this study suggest that the ALFF reflects the underlying neurovascular activity and has a great potential to estimate the brain tissue viability after ischemia. Results also show that the ALFF may contribute to acute stroke imaging for thrombolytic or neuroprotective therapies. PMID- 25121487 TI - Agricultural science in the wild: a social network analysis of farmer knowledge exchange. AB - Responding to demands for transformed farming practices requires new forms of knowledge. Given their scale and complexity, agricultural problems can no longer be solved by linear transfers in which technology developed by specialists passes to farmers by way of extension intermediaries. Recent research on alternative approaches has focused on the innovation systems formed by interactions between heterogeneous actors. Rather than linear transfer, systems theory highlights network facilitation as a specialized function. This paper contributes to our understanding of such facilitation by investigating the networks in which farmers discuss science. We report findings based on the study of a pastoral farming experiment collaboratively undertaken by a group of 17 farmers and five scientists. Analysis of prior contact and alter sharing between the group's members indicates strongly tied and decentralized networks. Farmer knowledge exchanges about the experiment have been investigated using a mix of quantitative and qualitative methods. Network surveys identified who the farmers contacted for knowledge before the study began and who they had talked to about the experiment by 18 months later. Open-ended interviews collected farmer statements about their most valuable contacts and these statements have been thematically analysed. The network analysis shows that farmers talked about the experiment with 192 people, most of whom were fellow farmers. Farmers with densely tied and occupationally homogeneous contacts grew their networks more than did farmers with contacts that are loosely tied and diverse. Thematic analysis reveals three general principles: farmers value knowledge delivered by persons rather than roles, privilege farming experience, and develop knowledge with empiricist rather than rationalist techniques. Taken together, these findings suggest that farmers deliberate about science in intensive and durable networks that have significant implications for theorizing agricultural innovation. The paper thus concludes by considering the findings' significance for current efforts to rethink agricultural extension. PMID- 25121488 TI - Efficacy and safety of rituximab in children with difficult-to-treat nephrotic syndrome. AB - BACKGROUND: Rituximab has emerged as an important medication for patients with steroid-dependent or steroid-resistant nephrotic syndrome. PATIENTS: We report the efficacy and safety of therapy with intravenous rituximab, administered once weekly for 2-4 doses, in 193 patients (mean age 10.9, range 2.2-18.7 years) with difficult-to-treat steroid dependence (n = 101), calcineurin inhibitor (CNI) dependent steroid resistance (n = 34) and CNI-resistant nephrotic syndrome (n = 58) managed at this center during 2006-13. OUTCOMES: Therapy in patients with steroid dependence and CNI-dependent steroid resistance led to significantly reduced relapse rates (respective mean difference 2.7 relapses/year and 2.2 relapses/year, corresponding to a decrease in relapses by 81.8 and 71.0%; both P < 0.0001). This resulted in a significant reduction in steroid requirement (mean difference 104.5 and 113.6 mg/kg/year, respectively; both P < 0.0001) and a trend to improved standard deviation scores for height (P = 0.069) and body mass index (P = 0.029). Remission was longer in patients with steroid dependence compared with CNI-dependent steroid resistance (median 16 versus 10 months; P < 0.0001). Prior response to cyclophosphamide predicted a lower risk of relapse in the former (hazard ratio, HR 0.56; P = 0.045); patients with initial resistance and CNI-dependent steroid resistance had increased risk of relapse (HR 2.66; P = 0.042). B-cell recovery, noted in 62.5% patients at 6 months, was not related to occurrence of relapse; redosing (n = 42 patients) was safe and effective. Response to therapy was unsatisfactory in patients with steroid- and CNI resistant nephrotic syndrome, with remission in 29.3%. Focal segmental glomerulosclerosis was associated with higher odds of non-response (odds ratio 11.1; P = 0.028) and lack of response was associated with progressive chronic kidney disease (HR 9.97; P = 0.035). Therapy with rituximab was safe; adverse effects or infections were noted in 19 (9.8%) patients. CONCLUSIONS: Therapy with rituximab is effective and safe in reducing relapse rates and need for immunosuppressive medications in patients with steroid-dependent and CNI dependent steroid-resistant nephrotic syndrome. PMID- 25121489 TI - Distribution of schistosomiasis and soil transmitted helminthiasis in Zimbabwe: towards a national plan of action for control and elimination. AB - BACKGROUND: Schistosomiasis and STH are among the list of neglected tropical diseases considered for control by the WHO. Although both diseases are endemic in Zimbabwe, no nationwide control interventions have been implemented. For this reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two diseases in the 2009-2013 National Health Strategy highlighting the importance of understanding the distribution and burden of the diseases as a prerequisite for elimination interventions. It is against this background that a national survey was conducted. METHODOLOGY: A countrywide cross-sectional survey was carried out in 280 primary schools in 68 districts between September 2010 and August 2011. Schistosoma haematobium was diagnosed using the urine filtration technique. Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris lumbricoides) were diagnosed using both the Kato Katz and formol ether concentration techniques. MAIN FINDINGS: Schistosomiasis was more prevalent country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0% while that of S. mansoni was 7.2%. Hookworms were the most common STH with a prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as defined by WHO for any schistosome species was 5.8% (range 0%-18.3% in districts). Only light to moderate infection intensities were observed for STH species. The distribution of schistosomiasis and STH varied significantly between provinces, districts and schools (p<0.001). Overall, the prevalence of co infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened. CONCLUSION AND RECOMMENDATIONS: This study provided comprehensive baseline data on the distribution of schistosomiasis and STH that formed the basis for initiating a national control and elimination programme for these two neglected tropical diseases in Zimbabwe. PMID- 25121490 TI - Phenotypic robustness and the assortativity signature of human transcription factor networks. AB - Many developmental, physiological, and behavioral processes depend on the precise expression of genes in space and time. Such spatiotemporal gene expression phenotypes arise from the binding of sequence-specific transcription factors (TFs) to DNA, and from the regulation of nearby genes that such binding causes. These nearby genes may themselves encode TFs, giving rise to a transcription factor network (TFN), wherein nodes represent TFs and directed edges denote regulatory interactions between TFs. Computational studies have linked several topological properties of TFNs - such as their degree distribution - with the robustness of a TFN's gene expression phenotype to genetic and environmental perturbation. Another important topological property is assortativity, which measures the tendency of nodes with similar numbers of edges to connect. In directed networks, assortativity comprises four distinct components that collectively form an assortativity signature. We know very little about how a TFN's assortativity signature affects the robustness of its gene expression phenotype to perturbation. While recent theoretical results suggest that increasing one specific component of a TFN's assortativity signature leads to increased phenotypic robustness, the biological context of this finding is currently limited because the assortativity signatures of real-world TFNs have not been characterized. It is therefore unclear whether these earlier theoretical findings are biologically relevant. Moreover, it is not known how the other three components of the assortativity signature contribute to the phenotypic robustness of TFNs. Here, we use publicly available DNaseI-seq data to measure the assortativity signatures of genome-wide TFNs in 41 distinct human cell and tissue types. We find that all TFNs share a common assortativity signature and that this signature confers phenotypic robustness to model TFNs. Lastly, we determine the extent to which each of the four components of the assortativity signature contributes to this robustness. PMID- 25121494 TI - Total internal and external ophthalmoplegia as presenting symptoms of Miller Fisher syndrome. PMID- 25121492 TI - A simple model of optimal population coding for sensory systems. AB - A fundamental task of a sensory system is to infer information about the environment. It has long been suggested that an important goal of the first stage of this process is to encode the raw sensory signal efficiently by reducing its redundancy in the neural representation. Some redundancy, however, would be expected because it can provide robustness to noise inherent in the system. Encoding the raw sensory signal itself is also problematic, because it contains distortion and noise. The optimal solution would be constrained further by limited biological resources. Here, we analyze a simple theoretical model that incorporates these key aspects of sensory coding, and apply it to conditions in the retina. The model specifies the optimal way to incorporate redundancy in a population of noisy neurons, while also optimally compensating for sensory distortion and noise. Importantly, it allows an arbitrary input-to-output cell ratio between sensory units (photoreceptors) and encoding units (retinal ganglion cells), providing predictions of retinal codes at different eccentricities. Compared to earlier models based on redundancy reduction, the proposed model conveys more information about the original signal. Interestingly, redundancy reduction can be near-optimal when the number of encoding units is limited, such as in the peripheral retina. We show that there exist multiple, equally-optimal solutions whose receptive field structure and organization vary significantly. Among these, the one which maximizes the spatial locality of the computation, but not the sparsity of either synaptic weights or neural responses, is consistent with known basic properties of retinal receptive fields. The model further predicts that receptive field structure changes less with light adaptation at higher input-to-output cell ratios, such as in the periphery. PMID- 25121491 TI - Is Plasmodium vivax malaria a severe malaria?: a systematic review and meta analysis. AB - BACKGROUND: Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection. METHODS/PRINCIPAL FINDINGS: We searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04-5.68, I2:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83-5.1, I2:83%), the 5-15 year-age group (OR: 0.6, 95% CI: 0.31-1.16, I2:81%) and adults (OR: 0.83, 95% CI: 0.67-1.03, I2:25%). Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64-18.94, I2: 92%), the 5-15 year-age group (OR:0.71, 95% CI: 0.06-8.57, I2:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62-0.92, I2:0%). Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5-0.76, I2:0%), while this was comparable in the 5-15 year- age group (OR: 0.43, 95% CI:0.06-2.91, I2:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59-1.01, I2:0%). CONCLUSION: Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt early detection. Subsequent treatment and monitoring of complications can be life-saving. PMID- 25121493 TI - Hyperglycemia and blood pressure treatment goal: a cross sectional survey of 18350 patients with type 2 diabetes in 77 tertiary hospitals in China. AB - OBJECTIVE: To investigate the association of hyperglycemia with blood pressure control goal in the patients with type 2 diabetes (T2D) cared by tertiary hospitals in China. STUDY DESIGN AND METHODS: A cross sectional survey of 29442 patients was conducted in 77 tertiary hospitals in 4 major cities in China in 2011 and 18350 of them without known hypertension were used in the analysis. Univariable and multivariable logistic regression analysis stratified on cities and hospitals was performed to obtain odds ratio of factors of interest for achievement of the blood pressure treatment goal, i.e., 140/80 mmHg as recommended by American Diabetes Association (ADA). Sensitivity analysis was performed after re-inclusion of 11902 patients with diagnosed hypertension. Findings from were further replicated in patients with T2D recruited using the same protocol from tertiary hospitals located in other central cities in China. RESULTS: The mean age was 58.2 (SD: 11.3) years and 53.3% were male, with a median of 4 years of disease duration. A total of 12129 patients (58.2%) did not achieve the ADA recommended goal for BP control. After adjusting for covariables, hyperglycemia was associated with failure to achieve the BP goal (OR of HbA1c at 6.5%-6.9% vs. <6.0%: 1.22, 95%CI: 1.08 to 1.39; OR of 7.0%-7.0% vs. <6.0%: 1.37, 1.21 to 1.54 and OR of >= 8.0% vs. <6.0%: 1.22, 95%CI: 1.08 to 1.38). The sensitivity analysis and the replication analysis showed similar results. CONCLUSIONS: Hyperglycemia defined as HbA1c >= 6.5% increased the risk of failure to achieve the BP goal in T2D patients. PMID- 25121495 TI - Phylobetadiversity among forest types in the Brazilian Atlantic Forest complex. AB - Phylobetadiversity is defined as the phylogenetic resemblance between communities or biomes. Analyzing phylobetadiversity patterns among different vegetation physiognomies within a single biome is crucial to understand the historical affinities between them. Based on the widely accepted idea that different forest physiognomies within the Southern Brazilian Atlantic Forest constitute different facies of a single biome, we hypothesize that more recent phylogenetic nodes should drive phylobetadiversity gradients between the different forest types within the Atlantic Forest, as the phylogenetic divergence among those forest types is biogeographically recent. We compiled information from 206 checklists describing the occurrence of shrub/tree species across three different forest physiognomies within the Southern Brazilian Atlantic Forest (Dense, Mixed and Seasonal forests). We analyzed intra-site phylogenetic structure (phylogenetic diversity, net relatedness index and nearest taxon index) and phylobetadiversity between plots located at different forest types, using five different methods differing in sensitivity to either basal or terminal nodes (phylogenetic fuzzy weighting, COMDIST, COMDISTNT, UniFrac and Rao's H). Mixed forests showed higher phylogenetic diversity and overdispersion than the other forest types. Furthermore, all forest types differed from each other in relation phylobetadiversity patterns, particularly when phylobetadiversity methods more sensitive to terminal nodes were employed. Mixed forests tended to show higher phylogenetic differentiation to Dense and Seasonal forests than these latter from each other. The higher phylogenetic diversity and phylobetadiversity levels found in Mixed forests when compared to the others likely result from the biogeographical origin of several taxa occurring in these forests. On one hand, Mixed forests shelter several temperate taxa, like the conifers Araucaria and Podocarpus. On the other hand, tropical groups, like Myrtaceae, are also very representative of this forest type. We point out to the need of more attention to Mixed forests as a conservation target within the Brazilian Atlantic Forest given their high phylogenetic uniqueness. PMID- 25121496 TI - Corneal viscoelastic properties from finite-element analysis of in vivo air-puff deformation. AB - Biomechanical properties are an excellent health marker of biological tissues, however they are challenging to be measured in-vivo. Non-invasive approaches to assess tissue biomechanics have been suggested, but there is a clear need for more accurate techniques for diagnosis, surgical guidance and treatment evaluation. Recently air-puff systems have been developed to study the dynamic tissue response, nevertheless the experimental geometrical observations lack from an analysis that addresses specifically the inherent dynamic properties. In this study a viscoelastic finite element model was built that predicts the experimental corneal deformation response to an air-puff for different conditions. A sensitivity analysis reveals significant contributions to corneal deformation of intraocular pressure and corneal thickness, besides corneal biomechanical properties. The results show the capability of dynamic imaging to reveal inherent biomechanical properties in vivo. Estimates of corneal biomechanical parameters will contribute to the basic understanding of corneal structure, shape and integrity and increase the predictability of corneal surgery. PMID- 25121499 TI - NICE supports allowing technology assessment bodies to provide advice to drug industry. PMID- 25121498 TI - Variation in the fitness effects of mutations with population density and size in Escherichia coli. AB - The fitness effects of mutations are context specific and depend on both external (e.g., environment) and internal (e.g., cellular stress, genetic background) factors. The influence of population size and density on fitness effects are unknown, despite the central role population size plays in the supply and fixation of mutations. We addressed this issue by comparing the fitness of 92 Keio strains (Escherichia coli K12 single gene knockouts) at comparatively high (1.2*10(7) CFUs/mL) and low (2.5*10(2) CFUs/mL) densities, which also differed in population size (high: 1.2*10(8); low: 1.25*10(3)). Twenty-eight gene deletions (30%) exhibited a fitness difference, ranging from 5 to 174% (median: 35%), between the high and low densities. Our analyses suggest this variation among gene deletions in fitness responses reflected in part both gene orientation and function, of the gene properties we examined (genomic position, length, orientation, and function). Although we could not determine the relative effects of population density and size, our results suggest fitness effects of mutations vary with these two factors, and this variation is gene-specific. Besides being a mechanism for density-dependent selection (r-K selection), the dependence of fitness effects on population density and size has implications for any population that varies in size over time, including populations undergoing evolutionary rescue, species invasions into novel habitats, and cancer progression and metastasis. Further, combined with recent advances in understanding the roles of other context-specific factors in the fitness effects of mutations, our results will help address theoretical and applied biological questions more realistically. PMID- 25121497 TI - Schistosome feeding and regurgitation. AB - Schistosomes are parasitic flatworms that infect >200 million people worldwide, causing the chronic, debilitating disease schistosomiasis. Unusual among parasitic helminths, the long-lived adult worms, continuously bathed in blood, take up nutrients directly across the body surface and also by ingestion of blood into the gut. Recent proteomic analyses of the body surface revealed the presence of hydrolytic enzymes, solute, and ion transporters, thus emphasising its metabolic credentials. Furthermore, definition of the molecular mechanisms for the uptake of selected metabolites (glucose, certain amino acids, and water) establishes it as a vital site of nutrient acquisition. Nevertheless, the amount of blood ingested into the gut per day is considerable: for males ~100 nl; for the more actively feeding females ~900 nl, >4 times body volume. Ingested erythrocytes are lysed as they pass through the specialized esophagus, while leucocytes become tethered and disabled there. Proteomics and transcriptomics have revealed, in addition to gut proteases, an amino acid transporter in gut tissue and other hydrolases, ion, and lipid transporters in the lumen, implicating the gut as the site for acquisition of essential lipids and inorganic ions. The surface is the principal entry route for glucose, whereas the gut dominates amino acid acquisition, especially in females. Heme, a potentially toxic hemoglobin degradation product, accumulates in the gut and, since schistosomes lack an anus, must be expelled by the poorly understood process of regurgitation. Here we place the new observations on the proteome of body surface and gut, and the entry of different nutrient classes into schistosomes, into the context of older studies on worm composition and metabolism. We suggest that the balance between surface and gut in nutrition is determined by the constraints of solute diffusion imposed by differences in male and female worm morphology. Our conclusions have major implications for worm survival under immunological or pharmacological pressure. PMID- 25121501 TI - Hypertrophic chondrocytes in the rabbit growth plate can proliferate and differentiate into osteogenic cells when capillary invasion is interposed by a membrane filter. AB - The fate of hypertrophic chondrocytes during endochondral ossification remains controversial. It has long been thought that the calcified cartilage is invaded by blood vessels and that new bone is deposited on the surface of the eroded cartilage by newly arrived cells. The present study was designed to determine whether hypertrophic chondrocytes were destined to die or could survive to participate in new bone formation. In a rabbit experiment, a membrane filter with a pore size of 1 um was inserted in the middle of the hypertrophic zone of the distal growth plate of ulna. In 33 of 37 animals, vascular invasion was successfully interposed by the membrane filter. During 8 days, the cartilage growth plate was enlarged, making the thickness 3-fold greater than that of the nonoperated control side. Histological examination demonstrated that the hypertrophic zone was exclusively elongated. At the terminal end of the growth plate, hypertrophic chondrocytes extruded from their territorial matrix into the open cavity on the surface of the membrane filter. The progenies of hypertrophic chondrocytes (PHCs) were PCNA positive and caspase-3 negative. In situ hybridization studies demonstrated that PHCs did not express cartilage matrix proteins anymore but expressed bone matrix proteins. Immunohistochemical studies also demonstrated that the new matrix produced by PHCs contained type I collagen, osteonectin, and osteocalcin. Based on these results, we concluded that hypertrophic chondrocytes switched into bone-forming cells after vascular invasion was interposed in the normal growth plate. PMID- 25121500 TI - The relationship between muscle fiber type-specific PGC-1alpha content and mitochondrial content varies between rodent models and humans. AB - PGC-1alpha regulates critical processes in muscle physiology, including mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, PGC 1alpha was suggested as an important regulator of fiber type determination. However, whether a muscle fiber type-specific PGC-1alpha content exists, whether PGC-1alpha content relates to basal levels of mitochondrial content, and whether such relationships are preserved between humans and classically used rodent models are all questions that have been either poorly addressed or never investigated. To address these issues, we investigated the fiber type-specific content of PGC-1alpha and its relationship to basal mitochondrial content in mouse, rat and human muscles using in situ immunolabeling and histochemical methods on muscle serial cross-sections. Whereas type IIa fibers exhibited the highest PGC-1alpha in all three species, other fiber types displayed a hierarchy of type IIx>I>IIb in mouse, type I = IIx> IIb in rat, and type IIx>I in human. In terms of mitochondrial content, we observed a hierarchy of IIa>IIx>I>IIb in mouse, IIa >I>IIx> IIb in rat, and I>IIa> IIx in human skeletal muscle. We also found in rat skeletal muscle that type I fibers displayed the highest capillarization followed by type IIa >IIx>IIb. Finally, we found in human skeletal muscle that type I fibers display the highest lipid content, followed by type IIa>IIx. Altogether, our results reveal that (i) the fiber type-specific PGC 1alpha and mitochondrial contents were only matched in mouse, (ii) the patterns of PGC-1alpha and mitochondrial contents observed in mice and rats do not correspond to that seen in humans in several respects, and (iii) the classical phenotypes thought to be regulated by PGC-1alpha do not vary exclusively as a function of PGC-1alpha content in rat and human muscles. PMID- 25121502 TI - Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells. AB - Four and a Half LIM protein 2 (FHL2) is a LIM domain only protein that is able to form various protein complexes and regulate gene transcription. Recent findings showed that FHL2 is a potential tumor suppressor gene that was down-regulated in hepatocellular carcinoma (HCC). Moreover, FHL2 can bind to and activate the TP53 promoter in hepatic cells. In this study, the activity of the two promoters of FHL2, 1a and 1b, were determined in the human embryonic kidney cell line HEK293 and the activation of these two promoters by p53 was investigated. Our results showed that the 1b promoter has a higher activity than the 1a promoter in HEK 293 cells but the 1a promoter is more responsive to the activation by p53 when compared with the 1b promoter. The regulation of FHL2 by p53 was further confirmed in liver cells by the overexpression of p53 in Hep3B cells and the knockdown of p53 in HepG2 cells. Combining promoter activity results of truncated mutants and predictions by bioinformatics tools, a putative p53 binding site was found in the exon 1a of FHL2 from +213 to +232. The binding between the p53 protein and the putative p53 binding site was then validated by the ChIP assay. Furthermore, the expression of FHL2 and TP53 were down-regulated in majority of HCC tumour samples (n = 41) and significantly correlated (P = 0.026). Finally, we found that the somatic mutation 747 (G->T), a hot spot mutation of the TP53 gene, is potentially associated with a higher expression of FHL2 in HCC tumour samples. Taken together, this is the first in-depth study about the transcriptional regulation of FHL2 by p53. PMID- 25121503 TI - Low intensity, high frequency vibration training to improve musculoskeletal function in a mouse model of Duchenne muscular dystrophy. AB - The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P >= 0.34). Vibration did not alter any measure of muscle contractile function (P >= 0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice. PMID- 25121505 TI - Pleiotropic effects of a methyl donor diet in a novel animal model. AB - Folate and other methyl-donor pathway components are widely supplemented due to their ability to prevent prenatal neural tube defects. Several lines of evidence suggest that these supplements act through epigenetic mechanisms (e.g. altering DNA methylation). Primary among these are the experiments on the mouse viable yellow allele of the agouti locus (A(vy)). In the Avy allele, an Intracisternal A particle retroelement has inserted into the genome adjacent to the agouti gene and is preferentially methylated. To further test these effects, we tested the same diet used in the Avy studies on wild-derived Peromyscus maniculatus, a native North American rodent. We collected tissues from neonatal offspring whose parents were fed the high-methyl donor diet as well as controls. In addition, we assayed coat-color of a natural variant (wide-band agouti = A(Nb)) that overexpresses agouti as a phenotypic biomarker. Our data indicate that these dietary components affected agouti protein production, despite the lack of a retroelement at this locus. Surprisingly, the methyl-donor diet was associated with defects (e.g. ovarian cysts, cataracts) and increased mortality. We also assessed the effects of the diet on behavior: We scored animals in open field and social interaction tests. We observed significant increases in female repetitive behaviors. Thus these data add to a growing number of studies that suggest that these ubiquitously added nutrients may be a human health concern. PMID- 25121507 TI - We are both doctors: a Palestinian doctor writes to an Israeli colleague. PMID- 25121504 TI - Phosphorylation of a central clock transcription factor is required for thermal but not photic entrainment. AB - Transcriptional/translational feedback loops drive daily cycles of expression in clock genes and clock-controlled genes, which ultimately underlie many of the overt circadian rhythms manifested by organisms. Moreover, phosphorylation of clock proteins plays crucial roles in the temporal regulation of clock protein activity, stability and subcellular localization. dCLOCK (dCLK), the master transcription factor driving cyclical gene expression and the rate-limiting component in the Drosophila circadian clock, undergoes daily changes in phosphorylation. However, the physiological role of dCLK phosphorylation is not clear. Using a Drosophila tissue culture system, we identified multiple phosphorylation sites on dCLK. Expression of a mutated version of dCLK where all the mapped phospho-sites were switched to alanine (dCLK-15A) rescues the arrythmicity of Clk(out) flies, yet with an approximately 1.5 hr shorter period. The dCLK-15A protein attains substantially higher levels in flies compared to the control situation, and also appears to have enhanced transcriptional activity, consistent with the observed higher peak values and amplitudes in the mRNA rhythms of several core clock genes. Surprisingly, the clock-controlled daily activity rhythm in dCLK-15A expressing flies does not synchronize properly to daily temperature cycles, although there is no defect in aligning to light/dark cycles. Our findings suggest a novel role for clock protein phosphorylation in governing the relative strengths of entraining modalities by adjusting the dynamics of circadian gene expression. PMID- 25121506 TI - Folliculin regulates cell-cell adhesion, AMPK, and mTORC1 in a cell-type-specific manner in lung-derived cells. AB - Germline loss-of-function BHD mutations cause cystic lung disease and hereditary pneumothorax, yet little is known about the impact of BHD mutations in the lung. Folliculin (FLCN), the product of the Birt-Hogg-Dube (BHD) gene, has been linked to altered cell-cell adhesion and to the AMPK and mTORC1 signaling pathways. We found that downregulation of FLCN in human bronchial epithelial (HBE) cells decreased the phosphorylation of ACC, a marker of AMPK activation, while downregulation of FLCN in small airway epithelial (SAEC) cells increased the activity of phospho-S6, a marker of mTORC1 activation, highlighting the cell type dependent functions of FLCN. Cell-cell adhesion forces were significantly increased in FLCN-deficient HBE cells, consistent with prior findings in FLCN deficient human kidney-derived cells. To determine how these altered cell-cell adhesion forces impact the lung, we exposed mice with heterozygous inactivation of Bhd (similarly to humans with germline inactivation of one BHD allele) to mechanical ventilation at high tidal volumes. Bhd(+/-) mice exhibited a trend (P = 0.08) toward increased elastance after 6 h of ventilation at 24 cc/kg. Our results indicate that FLCN regulates the AMPK and mTORC1 pathways and cell-cell adhesion in a cell type-dependent manner. FLCN deficiency may impact the physiologic response to inflation-induced mechanical stress, but further investigation is required. We hypothesize that FLCN-dependent effects on signaling and cellular adhesion contribute to the pathogenesis of cystic lung disease in BHD patients. PMID- 25121508 TI - Changes in corneal deformation parameters after lenticule creation and extraction during small incision lenticule extraction (SMILE) procedure. AB - PURPOSE: To investigate the effects of lenticule creation and subsequent corneal lenticule extraction on corneal deformation parameters during small incision lenticule extraction (SMILE) procedure. MATERIALS AND METHODS: In this prospective study, 18 eyes of 10 patients (27.90 +/- 7.11 years, -5.64 +/- 2.45 diopters) scheduled for SMILE procedure were enrolled. Changes in the corneal deformation parameters, including deformation amplitude (DA), applanation time(AT1 and AT2), applanation length(AL1 and AL2), corneal velocity(CV1 and CV2), peak distance(P.Dist.), radius and intraocular pressure values were measured preoperatively, immediately after lenticule creation and subsequent to corneal lenticule extraction in all eyes with the Corvis Scheimpflug Technology (Corvis ST, OCULUS, Wetzlar, Germany). Repeated measures analysis of variance (ANOVA) with bonferroni-adjusted post hoc comparisons was performed to investigate changes following each step of the procedure. RESULTS: All surgical procedures were uneventful. A significant difference was detected among the three time points (pre-operation, post-lenticule creation and post lenticule extraction) for AT1 (P<0.001), AT2 (P = 0.001), DA(P<0.001), and IOP(P = 0.002). Bonferroni-adjusted post hoc comparisons indicated that there was no significant change in AT1, AT2, DA, or IOP after lenticule creation (post hoc P>0.05), but there was a significant change in these parameters following subsequent corneal lenticule extraction (post hoc P<0.01), when compared to values obtained pre operatively. The scheimpflug camera of the Corvis ST demonstrated the intralamellar small gas bubbles formed from the vaporisation of tissue after lenticule creation and a gray zone was observed between the cap and the residual stromal bed after lenticule extraction. CONCLUSIONS: There is a significant change in corneal deformation parameters following SMILE procedure. The changes may be caused predominantly by stromal lenticule extraction, while lenticule creation with femtosecond laser may not have an obvious effect on corneal deformation properties. PMID- 25121509 TI - Intraosseous fixation compared to plantar plate fixation for first metatarsocuneiform arthrodesis: a cadaveric biomechanical analysis. AB - BACKGROUND: Metatarsocuneiform (MTC) fusion is a treatment option for management of hallux valgus. We compared the biomechanical characteristics of an internal fixation device with plantar plate fixation. METHODS: Seven matched pairs of feet from human cadavers were used to compare the intramedullary (IM) device plus compression screw to plantar plate combined with a compression screw. Specimen constructs were loaded in a cyclic 4-point bending test. We obtained initial/final stiffness, maximum load, and number of cycles to failure. Bone mineral density was measured with peripheral quantitative computed tomography. Performance was compared using time to event analysis with number of cycles as time variable, and a proportional hazard model including shared frailty model fitted with treatment and bone mineral density as covariates. RESULTS: On average the plates failed after 7517 cycles and a maximum load of 167 N, while the IM implants failed on average after 2946 cycles and a maximum load of 69 N. In all pairs the 1 treated with IM-implant failed earlier than the 1 treated with a plate (hazard ratio for IM-implant versus plate was 79.9 (95% confidence interval [6.1, 1052.2], P = .0009). The initial stiffness was 131 N/mm for the plantar plate and 43.3 N/mm for the IM implant. Initial stiffness (r = .955) and final stiffness (r = .952) were strongly related to the number of cycles to failure. Bone mineral density had no effect on the number of cycles to failure. CONCLUSION: Plantar plate fixation created a stronger and stiffer construct than IM fixation. CLINICAL RELEVANCE: A stiffer construct can reduce the risk of nonunion and shorten the period of non-weight-bearing. PMID- 25121510 TI - Early results with LifeStent implantation in RESILIENT and non-RESILIENT inclusion criteria patients. AB - The purpose of our study was to determine outcomes of patients receiving the LifeStent (Bard Peripheral Vascular, Tempe, AZ) for femoropopliteal peripheral arterial disease in real-world academic practice outside the limitations of an industry supported trial. All patients from 2009 to 2012 at our institution who received a LifeStent during endovascular interventions and had follow-up were included. Outcomes evaluated included patency and freedom from limb loss. A total of 166 limbs in 151 patients had the LifeStent implanted in de novo vessels (54% male; 68 +/- 12 years). Eighty-percent of limbs did not meet RESILIENT criteria due to Rutherford category >3 (51%), TransAtlantic Inter-Society Consensus II classifications C/ D (51%), zero runoff vessels (6%), or stent location (17%). Primary patency rates were 81% at 6 months and 58% at 12 months with predictors for primary patency loss at 1 year including Rutherford category >3 (HR: 1.8 (95% CI: 1.0-3.1), p = 0.04), tobacco use (HR: 1.8 (95% CI: 1.0-3.3), p = 0.04), and no clopidogrel at discharge (HR: 3.2 (95% CI: 1.6-6.7), p < 0.01). A preintervention Rutherford category >3 predicted 24-month limb loss (HR, 16.0 (95% CI: 2.0-122.0), p < 0.01). The LifeStent is a viable option regardless of the TransAtlantic Inter-Society Consensus II classification; however, critical limb ischemia, current tobacco use, and absence of clopidogrel on discharge predict decreased patency on follow-up. PMID- 25121512 TI - Diabetes prescribing in England consumes nearly 10% of primary care budget. PMID- 25121511 TI - Developing an internationally-applicable service specification for continence care: systematic review, evidence synthesis and expert consensus. AB - BACKGROUND: Global demographic trends suggest that the incidence of both urinary and faecal incontinence will rise in the coming years, bringing significant health and economic implications for both patients and payers. There is limited organisational evidence to guide payers and providers about service configuration which will deliver efficient guideline-compliant, high-quality patient care. OBJECTIVES: To create, using evidence from a systematic review, qualitative data and expert consensus an internationally applicable service specification for continence care. METHOD: Evidence was obtained from a systematic and grey literature review of published randomised controlled trials and quasi experimental studies reporting efficacy of continence service design at the level of the community dwelling patient with either bladder or bowel incontinence, governmental reports and policy frameworks supplemented by data from 47 semi structured interviews with clinicians, patients, patient-representatives and policy experts from four geographies broadly representative of different healthcare systems. RESULTS: A number of themes related to current and potential future organisation of continence care were identified from the data. A modular service specification with eight core components was created including case detection, initial assessment and treatment, case co-ordination, caregiver support, community-based support, specialist assessment and treatment, use of containment products, and use of technology. Within this framework important key recommendations are: ensure robust referral pathways, shift assessment for case coordination to nurses specializing in continence care, promote self-management and technology, use comprehensive assessment tools and service performance targets based on outcome and operational measures. CONCLUSIONS: This study has defined practice gaps in the provision of continence services and described eight core components of a service specification for incontinence that commissioners and payers of health and social care could consider using to provide high-quality continence care. A shift towards a community-delivered, nurse-led model appears to be associated with clinical and cost-effective care for people with bladder and bowel incontinence. PMID- 25121514 TI - The development of the pediatric NAFLD fibrosis score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease. AB - BACKGROUND: Noninvasive hepatic fibrosis scores that predict the presence of advanced fibrosis have been developed and validated in adult patients with NAFLD. The aims of our study were to assess the utility of commonly used adult fibrosis scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that can predict advanced fibrosis. METHODS: Consecutive children with biopsy-proven NAFLD were included. Fibrosis was determined by an experienced pathologist (F0 4). Advanced fibrosis was defined as fibrosis stage >= 3. The following adult fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 Index. Multivariable logistic regression analysis was performed to build a new pediatric model for predicting advanced fibrosis. RESULTS: Our cohort consisted of 242 children with a mean age of 12.4 +/- 3.1 years and 63% were female. 36 (15%) subjects had advanced fibrosis. APRI and FIB-4 were higher in patients with advanced fibrosis compared to those with fibrosis stage 0-2; however, AST/ALT ratio and NFS were not different between the two groups. We used our data to develop a new model to predict advanced fibrosis which included: ALT, alkaline phosphatase, platelet counts and GGT. The multivariable logistic regression model (z) was defined as follows: z = 1.1+(0.34*sqrt(ALT))+(0.002*alkaline phosphatase) - (1.1*log(platelets) - (0.02*GGT). This value was then converted into a probability distribution (p) with a value between 0 to 100 by the following formula: p = 100 * exp(z)/[1+exp(z)]. The AUCROC for this model was 0.74 (95% CI: 0.66, 0.82). This was found to be significantly better than APRI, NAFLD Fibrosis Score and FIB-4 Index. CONCLUSION: Noninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing advanced fibrosis in children with NAFLD. We developed a new pediatric NAFLD fibrosis score with improved performance characteristics. PMID- 25121515 TI - Toxic peptides occur frequently in pergid and argid sawfly larvae. AB - Toxic peptides containing D-amino acids are reported from the larvae of sawfly species. The compounds are suspected to constitute environmental contaminants, as they have killed livestock grazing in areas with congregations of such larvae, and related larval extracts are deleterious to ants. Previously, two octapeptides (both called lophyrotomin) and three heptapeptides (pergidin, 4-valinepergidin and dephosphorylated pergidin) were identified from three species in the family Pergidae and one in Argidae. Here, the hypothesis of widespread occurrence of these peptides among sawflies was tested by LC-MS analyses of single larvae from eight pergid and 28 argid species, plus nine outgroup species. At least two of the five peptides were detected in most sawfly species, whereas none in any outgroup taxon. Wherever peptides were detected, they were present in each examined specimen of the respective species. Some species show high peptide concentrations, reaching up to 0.6% fresh weight of 4-valinepergidin (1.75 mg/larva) in the pergid Pterygophorus nr turneri. All analyzed pergids in the subfamily Pterygophorinae contained pergidin and 4-valinepergidin, all argids in Arginae contained pergidin and one of the two lophyrotomins, whereas none of the peptides was detected in any Perginae pergid or Sterictiphorinae argid (except in Schizocerella pilicornis, which contained pergidin). Three of the four sawfly species that were previously known to contain toxins were reanalyzed here, resulting in several, often strong, quantitative and qualitative differences in the chemical profiles. The most probable ecological role of the peptides is defense against natural enemies; the poisoning of livestock is an epiphenomenon. PMID- 25121516 TI - Distance-dependent association of affect with pacing strategy in cycling time trials. AB - The psychological construct of affect is proposed to significantly contribute to pacing decisions during exercise. Borg's RPE scale, another important regulator of work rate, is criticized as an inadequate measure of the multiple perceptual responses experienced. This study aimed to examine power output distribution and associated changes in affect, self-efficacy, perceptual cues, HR, and respiratory gases during both 16.1- and 40-km self-paced cycling time trials (TT). Secondly, the differentiation between physical perceptions of exertion and sense of effort in self-paced exercise was investigated. METHOD: Fifteen trained male cyclists completed 16.1- and 40-km TT using a CompuTrainer cycle ergometer. Time, power output distribution, affect, self-efficacy, physical RPE (P-RPE), task effort and awareness (TEA), HR, and respiratory gases were measured throughout each TT. Linear mixed models explored associations of these variables with power output distribution and the relationship between P-RPE and TEA. RESULTS: Similar pacing strategies were adopted in the 16.1- and 40-km TT (P = 0.31), and the main effects were found for affect (P = 0.001) and RER (P < 0.001). Interactions between affect (P = 0.037) and RER (P = 0.004), with condition, indicated closer associations with power output distribution in 16.1 km than that in 40 km TT. P RPE was not significantly different from TEA (P = 0.053). CONCLUSION: A significant association between affect and power output distribution suggests that affective responses are task dependent even in self-paced exercise, and a greater association is demonstrated in higher intensity, 16.1 km TT. Furthermore, physical perceptions of exertion are not clearly differentiated from the sense of effort in self-paced exercise. PMID- 25121517 TI - Comparison of step outputs for waist and wrist accelerometer attachment sites. AB - PURPOSE: The objective of this study is to compare step outputs obtained from waist and wrist accelerometer attachment sites under laboratory and free-living conditions. METHODS: Under the laboratory condition, participants concurrently wore ActiGraph accelerometers at their waist and nondominant wrist while walking/running at treadmill speeds between 14 and 188 m.min. Visually counted steps served as a criterion standard. Participants then wore both accelerometers for 7 d. All accelerometer step data were processed applying both the manufacturer's default and low-frequency extension filters. Paired sample t-tests were used to evaluate mean differences in criterion steps per minute and the four (attachment site * filter) estimates produced from the waist- and wrist-worn accelerometers in the laboratory study. Free-living differences in mean steps per day detected between the waist and wrist (considering both filters) were computed. RESULTS: Relative to visually counted steps, the waist attachment site generally outperformed the wrist attachment site at most speeds, regardless of the applied filtering process. Under free-living conditions, the waist-worn accelerometer detected 6743 +/- 2398 (default filter) and 13,029 +/- 3734 (low frequency extension) steps per day. The concurrently worn wrist accelerometer detected 9301 +/- 2887 (default filter) and 15,493 +/- 3958 (low-frequency extension) steps per day. CONCLUSION: The wrist attachment site detected consistently fewer visually counted steps than the waist attachment site at most treadmill speeds during laboratory testing. In contrast, the wrist attachment site produced a higher average step count (ranging from approximately 2500 to 8700 more steps per day under free-living conditions, dependent on the filtering process applied) than the waist attachment site under free-living conditions. In conclusion, step outputs obtained from waist- and wrist-worn accelerometer attachment sites are generally not comparable under either laboratory or free living conditions. PMID- 25121513 TI - Comparing interferon-gamma release assays to tuberculin skin test in Thai children with tuberculosis exposure. AB - BACKGROUND: Data on the performance of interferon-gamma release assays (IGRAs), QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis (TB) are limited in Southeast Asia. This study aims to compare the performances of the two IGRAs and TST in Thai children with recent TB exposure. METHODS: This multicenter, prospective study enrolled children with recent exposure to active TB adults. Children were investigated for active TB. TST was performed and blood collected for T-Spot.TB and QFNGIT. RESULTS: 158 children were enrolled (87% TB exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV infection. 66.7% had TST>=10 mm, while 38.6% had TST>=15 mm. 32.5% had positive QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher among children with active TB compared with TB-exposed children. No indeterminate IGRA results were detected. No statistically significant differences between the performances of the IGRAs and TST at the two cut-offs with increasing TB exposure were detected. Concordance for positive IGRAs and TST ranged from 42-46% for TST>=10 mm and 62-67% for TST>=15 mm. On multivariable analyses, exposure to household primary/secondary caregiver with TB was associated with positive QFNGIT. Higher TB contact score and active TB were associated with positive T Spot.TB. CONCLUSIONS: Both QFNGIT and T-Spot.TB performed well in our Thai pediatric study population. No differences in the performances between tests with increasing TB exposure were found. Due to accessibility and low cost, using TST may more ideal than IGRAs in diagnosing latent and active TB in healthy children in Thailand and other similar settings. PMID- 25121518 TI - Myotonic dystrophy: diagnosis, management and new therapies. AB - PURPOSE OF REVIEW: Myotonic dystrophies type 1 and type 2 are progressive multisystem genetic disorders with clinical and genetic features in common. Myotonic dystrophy type 1 is the most prevalent muscular dystrophy in adults and has a wide phenotypic spectrum. The average age of death in myotonic dystrophy type 1 is in the fifth decade. In comparison, myotonic dystrophy type 2 tends to cause a milder phenotype with later onset of symptoms and is less common than myotonic dystrophy type 1. Historically, patients with myotonic dystrophy type 1 have not received the medical and social input they need to maximize their quality and quantity of life. This review describes the improved understanding in the molecular and clinical features of myotonic dystrophy type 1 as well as the screening of clinical complications and their management. We will also discuss new potential genetic treatments. RECENT FINDINGS: An active approach to screening and management of myotonic dystrophies type 1 and type 2 requires a multidisciplinary medical, rehabilitative and social team. This process will probably improve morbidity and mortality for patients. Genetic treatments have been successfully used in in-vitro and animal models to reverse the physiological, histopathological and transcriptomic features. SUMMARY: Molecular therapeutics for myotonic dystrophy will probably bridge the translational gap between bench and bedside in the near future. There will still be a requirement for clinical screening of patients with myotonic dystrophy with proactive and systematic management of complications. PMID- 25121520 TI - Acute conditions, incidence and associated disability, United States - july 1971 june 1972. AB - During JuIy 1971-June 1972, an estimated 447,735,000 acute illnesses or injuries requiring either medical attention or reduced daily activity were experienced by the civilian, noninstitutionalized population of the United States. The incidence of new cases of acute conditions per 100 persons per year was 220.2, which is somewhat larger than the annual incidence rate of 210.1 conditions per 100 persons reported for the previous 12-month period. The increase in the incidence rate was accounted for primarily by a rise in acute respiratory illnesses from 110.3 per 100 persons in July 1970-June 1971 to 120.7 in July 1971-June 1972. A notable increase in the incidence rate of influenza-like illnesses for 39.0 to 47.5 was responsible for the most part for the increased incidence rate of acute respiratory illnesses. This report is one of an annual series of such reports on the incidence of acute illness or injury based on data collected in the Health Interview Survey. The last report, Series 10, No. 82, covered the period July 1970-June 1971; acute illness or injury reports in Series 10 are Numbers 1, 10, 15, 26, 38, 44, 54, 69, and 77. The incidence of acute conditions on a calendar year basis is presented in summary form in the Current Estimates reports Series 10, Numbers 52, 60, 63, 72, 79, and 85 for 1967 through-1972. PMID- 25121519 TI - cAMP regulates expression of the cyclic nucleotide transporter MRP4 (ABCC4) through the EPAC pathway. AB - Multidrug resistance protein 4 (MRP4/ABCC4) has been established as an independent regulator of cyclic AMP (cAMP) levels particularly in vascular smooth muscle cells and in hematopoietic cells. Here, we assessed whether cAMP in turn regulates MRP4. A significant upregulation of MRP4 mRNA and protein by long-term treatment with cAMP-enhancing agents was observed in HeLa cells, smooth muscle cells, and megakaryoblastic leukemia M07e cells. This upregulation was not affected by inhibition of protein kinase A, but could be reverted by inhibitors and siRNA of an alternative cAMP-signaling route involving exchange proteins activated by cyclic AMP (EPAC) and mitogen-activated protein kinases. A selective EPAC activator could equally induce MRP4. The transcriptional regulation was confirmed in a luciferase reporter gene assay using a vector containing a 1494-bp fragment of the promoter region of the MRP4/ABCC4 gene. Our results suggest that enhanced cAMP levels upregulate MRP4 expression, which can result in increased cAMP efflux. PMID- 25121522 TI - Stable boron nitride diamondoids as nanoscale materials. AB - We predict the stability of diamondoids made up of boron and nitrogen instead of carbon atoms. The results are based on quantum-mechanical calculations within density functional theory (DFT) and show some very distinct features compared to the regular carbon-based diamondoids. These features are evaluated with respect to the energetics and electronic properties of the boron nitride diamondoids as compared to the respective properties of the carbon-based diamondoids. We find that BN-diamondoids are overall more stable than their respective C-diamondoid counterparts. The electronic band-gaps (E(g)) of the former are overall lower than those for the latter nanostructures but do not show a very distinct trend with their size. Contrary to the lower C-diamondoids, the BN-diamondoids are semiconducting and show a depletion of charge on the nitrogen site. Their differences in the distribution of the molecular orbitals, compared to their carbon-based counterparts, offer additional bonding and functionalization possibilities. These tiny BN-based nanostructures could potentially be used as nanobuilding blocks complementing or substituting the C-diamondoids, based on the desired properties. An experimental realization of boron nitride diamondoids remains to show their feasibility. PMID- 25121523 TI - Electromagnetic modelization of spherical focusing on a one-dimensional grating thanks to a conical B-spline modal method. AB - Focusing light onto nanostructures thanks to spherical lenses is a first step in enhancing the field and is widely used in applications. Nonetheless, the electromagnetic response of such nanostructures, which have subwavelength patterns, to a focused beam cannot be described by the simple ray tracing formalism. Here, we present a method for computing the response to a focused beam, based on the B-spline modal method adapted to nanostructures in conical mounting. The eigenmodes are computed in each layer for both polarizations and are then combined for the computation of scattering matrices. The simulation of a Gaussian focused beam is obtained thanks to a truncated decomposition into plane waves computed on a single period, which limits the computation burden. PMID- 25121521 TI - Child pain catastrophizing mediates the relation between parent responses to pain and disability in youth with functional abdominal pain. AB - OBJECTIVES: Functional abdominal pain (FAP) in youth is associated with substantial impairment in functioning, and prior research has shown that overprotective parent responses can heighten impairment. Little is known about how a range of parental behaviors (overprotection, minimizing, and/or encouragement) in response to their child's pain interact with child coping characteristics (eg, catastrophizing) to influence functioning in youth with FAP. In this study, it was hypothesized that the relation between parenting factors and child disability would be mediated by children's levels of maladaptive coping (ie, pain catastrophizing). METHODS: Seventy-five patients with FAP presenting to a pediatric pain clinic and their caregivers participated in the study. Youth completed measures of pain intensity (Numeric Rating Scale), pain catastrophizing (Pain Catastrophizing Scale), and disability (Functional Disability Inventory). Caregivers completed measures of parent pain catastrophizing (Pain Catastrophizing Scale), and parent responses to child pain behaviors (Adult Responses to Child Symptoms: Protection, Minimizing, and Encouragement/Monitoring subscales). RESULTS: Increased functional disability was significantly related to higher child pain intensity, increased child and parent pain catastrophizing, and higher levels of encouragement/monitoring and protection. Parent minimization was not related to disability. Child pain catastrophizing fully mediated the relation between parent encouragement/monitoring and disability and partially mediated the relation between parent protectiveness and disability. CONCLUSIONS: The impact of parenting behaviors in response to FAP on child disability is determined, in part, by the child's coping style. Findings highlight a more nuanced understanding of the parent-child interaction in determining pain-related disability levels, which should be taken into consideration in assessing and treating youth with FAP. PMID- 25121524 TI - Projection operator method for biperiodic diffraction gratings with anisotropic/bianisotropic generalizations. AB - The "projection operator" method is a variation of the normal-vector method for simulating optical diffraction from biperiodic gratings. A projection operator defined by the normal vector is interpolated over the grating volume rather than interpolating the vector itself. This approach circumvents difficulties associated with sign reversals and discontinuities encountered with the normal vector method, and it facilitates implementation for general grating geometries. The method is readily extensible to anisotropic and bianisotropic materials. Several numerical examples of the new method are presented, including comparisons to previously published test cases. PMID- 25121525 TI - Intrinsic optical torque of cylindrical vector beams on Rayleigh absorptive spherical particles. AB - The intrinsic optical torque of a focused cylindrical vector beam on a Rayleigh absorptive spherical particle is calculated via the corrected dipole approximation. Numerical results show that, for the radially polarized input field, the torque is distributed in the focal plane strictly along the azimuthal direction anywhere except at the focus. This shows a completely different property from what is observed in the focusing of a circularly polarized beam, where a strong axial torque component arises. For other cylindrically polarized input fields, the torque tends to align itself along the radial direction, as the polarization angle (the angle between the electric vector and the radial direction) changes from 0 degrees to 90 degrees . When limited to considering the torque at the equilibrium position, we find that only for those input fields with polarization angles larger than 50 degrees , the particle experiences a nonzero torque at its equilibrium position. This is verified by showing quantitatively the effects of the polarization angle on the magnitude and orientation of the torque at the equilibrium position. PMID- 25121526 TI - Realization of hybrid compressive imaging strategies. AB - The tendency of natural scenes to cluster around low frequencies is not only useful in image compression, it also can prove advantageous in novel infrared and hyperspectral image acquisition. In this paper, we exploit this signal model with two approaches to enhance the quality of compressive imaging as implemented in a single-pixel compressive camera and compare these results against purely random acquisition. We combine projection patterns that can efficiently extract the model-based information with subsequent random projections to form the hybrid pattern sets. With the first approach, we generate low-frequency patterns via a direct transform. As an alternative, we also used principal component analysis of an image library to identify the low-frequency components. We present the first (to the best of our knowledge) experimental validation of this hybrid signal model on real data. For both methods, we acquire comparable quality of reconstructions while acquiring only half the number of measurements needed by traditional random sequences. The optimal combination of hybrid patterns and the effects of noise on image reconstruction are also discussed. PMID- 25121527 TI - Real-time and accurate rail wear measurement method and experimental analysis. AB - When a train is running on uneven or curved rails, it generates violent vibrations on the rails. As a result, the light plane of the single-line structured light vision sensor is not vertical, causing errors in rail wear measurements (referred to as vibration errors in this paper). To avoid vibration errors, a novel rail wear measurement method is introduced in this paper, which involves three main steps. First, a multi-line structured light vision sensor (which has at least two linear laser projectors) projects a stripe-shaped light onto the inside of the rail. Second, the central points of the light stripes in the image are extracted quickly, and the three-dimensional profile of the rail is obtained based on the mathematical model of the structured light vision sensor. Then, the obtained rail profile is transformed from the measurement coordinate frame (MCF) to the standard rail coordinate frame (RCF) by taking the three dimensional profile of the measured rail waist as the datum. Finally, rail wear constraint points are adopted to simplify the location of the rail wear points, and the profile composed of the rail wear points are compared with the standard rail profile in RCF to determine the rail wear. Both real data experiments and simulation experiments show that the vibration errors can be eliminated when the proposed method is used. PMID- 25121528 TI - Diffraction by nanocrystals II. AB - Nanocrystals with more than one molecule in the unit cell will generally crystallize with incomplete unit cells on the crystal surface. Previous results show that the ensemble-averaged diffraction by such crystals consists of a usual Bragg component and two other Bragg-like components due to the incomplete unit cells. Using an intrinsic flexibility in the definition of the incomplete-unit cell part of a crystal, the problem is formulated such that the magnitude of the Bragg-like components is minimized, which leads to a simpler and more useful interpretation of the diffraction. Simulations show the nature of the relative magnitudes of the diffraction components in different regions of reciprocal space and the effect of crystal faceting. PMID- 25121529 TI - High-order integral equation methods for problems of scattering by bumps and cavities on half-planes. AB - This paper presents high-order integral equation methods for the evaluation of electromagnetic wave scattering by dielectric bumps and dielectric cavities on perfectly conducting or dielectric half-planes. In detail, the algorithms introduced in this paper apply to eight classical scattering problems, namely, scattering by a dielectric bump on a perfectly conducting or a dielectric half plane, and scattering by a filled, overfilled, or void dielectric cavity on a perfectly conducting or a dielectric half-plane. In all cases field representations based on single-layer potentials for appropriately chosen Green functions are used. The numerical far fields and near fields exhibit excellent convergence as discretizations are refined-even at and around points where singular fields and infinite currents exist. PMID- 25121530 TI - Holographic particle sizing and locating by using Hilbert-Huang transform. AB - By using the Hilbert-Huang transform, a novel method is proposed to perform the task of particle sizing and axial locating directly from in-line digital holograms rather than reconstructing the optical field. The intensity distribution of the particle hologram is decomposed into intrinsic mode functions (IMFs) by the empirical mode decomposition. From the Hilbert spectrum of these IMFs, the axial location of the particle can be calculated by fitting the spectrum to a straight line, and the particle size can be derived from the singularities of the spectrum. Our method does not need to predefine any basis function; thus the whole process is fast and efficient. The validity and accuracy of the method are demonstrated by the numerical simulations and experiments. It is expected that this method can be used in on-line particle sizing and 3D tracking. PMID- 25121531 TI - Coherence filtering and revivals in x-ray waveguides: a communication-modes approach. AB - Waveguides for short-wavelength x-rays have been successfully employed for microbeam and nanobeam production and microscopy experiments. The coherence of hard x-ray sources is generally poor, and therefore the spatial coherence filtering characteristics of waveguides have been attractive for high-resolution microscopy experiments. To quantify the spatial coherence filtering properties of a waveguide, we here report a theoretical study of the propagation of a partially coherent beam in a waveguide in the paraxial approximation. By propagating the cross-spectral density function associated with the partially coherent field, we quantify in detail the evolution of the spatial coherence as the beam proceeds along the waveguide. The propagation is efficiently accomplished using the communication-modes formalism. The generality of the approach makes it suitable to study more complex phenomena such as the second-order Talbot self-imaging effect and coherence revivals in waveguides. Numerical results are shown for waveguides illuminated by partially coherent hard x-rays. PMID- 25121532 TI - Accelerating propagation properties of misplaced Hermite-Gaussian beams. AB - A new family of finite-energy accelerating beams was constructed through misplacing the Hermite polynomial and Gaussian window function. The closed-form solution of k-space spectra and paraxial propagation of these beams are derived from the Fourier transform and the scalar angle spectra integral. These beams have similar propagation properties to finite Airy beams and parabolic beams, but the accelerating trajectory is hyperbola rather than parabola. The beam family can be experimentally generated by exponentially truncating the high-order Hermite-Gaussian beams in the spatial domain. PMID- 25121533 TI - Optical phase under deep turbulence conditions. AB - The Markov approximation for waves in random media specifies that, under strong scintillation conditions, the optical field of unbounded waves has a normal probability distribution with zero mean. Using the coherence function provided by the Markov approximation, we calculate statistics of the phase of the optical field that accounts for the presence of multiple phase dislocations. We also develop and test a Monte Carlo model that generates the phase samples obeying these statistics. In contrast to numerous phase models described in the literature, this model generates discontinuous phase samples that contain optical vortices. PMID- 25121534 TI - Scaling perceived saturation. AB - Two psychophysical experiments were conducted at North Carolina State University (NCSU) and Rochester Institute of Technology (RIT) to obtain replicated perceived saturation data from color normal observers on the order of one unit of saturation. The same 37 Munsell sample sheets, including up to four references that had similar perceived saturation but different hue, were used in both experiments. Different assessment methods included presenting either four references simultaneously or only one reference at a time to observers and obtaining judged saturation magnitudes for the given Munsell samples. Four saturation models comprising Sab*, Suv*, CIECAM02, as well as Richter/Lubbe, were tested. CIECAM02 gave the best prediction of saturation for data obtained at NCSU while Sab* outperformed other models for the RIT data. For the combined dataset, Sab*, the Richter/Lubbe, and CIECAM02-based saturation models exhibited comparable performances. The Standardized Residual Sum of Squares index was used to measure the inter- and intra-observer variability and goodness of fit. Inter- and intra-observer variability of assessments was smaller than or comparable to those reported for the typical color difference evaluation experiments. PMID- 25121535 TI - Light scattering by three-dimensional objects with semi-hard boundaries. AB - We introduce analytical models for scattering potentials of particles that have ellipsoid-, cylinder-, and parallelepiped-like shapes and adjustable edge sharpness with the help of the three-dimensional versions of the multi-Gaussian functions. The far fields produced upon scattering from such potentials are examined in detail and are shown to qualitatively and quantitatively depend on the scatterer's symmetry type as well as its orientation and edge sharpness. PMID- 25121536 TI - Backscatter analysis based algorithms for increasing transmission through highly scattering random media using phase-only-modulated wavefronts. AB - Recent theoretical and experimental advances have shed light on the existence of so-called "perfectly transmitting" wavefronts with transmission coefficients close to 1 in strongly backscattering random media. These perfectly transmitting eigen-wavefronts can be synthesized by spatial amplitude and phase modulation. Here, we consider the problem of transmission enhancement using phase-only modulated wavefronts. Motivated by biomedical applications, in which it is not possible to measure the transmitted fields, we develop physically realizable iterative and non-iterative algorithms for increasing the transmission through such random media using backscatter analysis. We theoretically show that, despite the phase-only modulation constraint, the non-iterative algorithms will achieve at least about 25pi%~78.5% transmission with very high probability, assuming that there is at least one perfectly transmitting eigen-wavefront and that the singular vectors of the transmission matrix obey the maximum entropy principle such that they are isotropically random. We numerically analyze the limits of phase-only-modulated transmission in 2D with fully spectrally accurate simulators and provide rigorous numerical evidence confirming our theoretical prediction in random media, with periodic boundary conditions, that is composed of hundreds of thousands of non-absorbing scatterers. We show via numerical simulations that the iterative algorithms we have developed converge rapidly, yielding highly transmitting wavefronts while using relatively few measurements of the backscatter field. Specifically, the best performing iterative algorithm yields ~70% transmission using just 15-20 measurements in the regime, where the non iterative algorithms yield ~78.5% transmission, but require measuring the entire modal reflection matrix. Our theoretical analysis and rigorous numerical results validate our prediction that phase-only modulation with a given number of spatial modes will yield higher transmission than amplitude and phase modulation with half as many modes. PMID- 25121538 TI - Electromagnetic energy within coated cylinders at oblique incidence and applications to graphene coatings. AB - We address electromagnetic (EM) wave scattering by an infinite coated cylinder at an arbitrary incidence angle. The time-averaged EM energy stored inside the core shell cylinder is analytically calculated for TM- and TE-polarized incident plane waves. An analytical expression relating the internal energy to the absorption cross section is derived. As an application, the EM energy inside dielectric cylinders coated with isotropic graphene layers epitaxially grown on silicon carbide (SiC) is studied. We find that off-resonance field enhancement occurs in graphene SiC microshells for TM-polarized terahertz waves, a phenomenon that can be explained in terms of Fano resonances. PMID- 25121537 TI - Wavefront reconstruction in phase-shifting interferometry via sparse coding of amplitude and absolute phase. AB - Phase-shifting interferometry is a coherent optical method that combines high accuracy with high measurement speeds. This technique is therefore desirable in many applications such as the efficient industrial quality inspection process. However, despite its advantageous properties, the inference of the object amplitude and the phase, herein termed wavefront reconstruction, is not a trivial task owing to the Poissonian noise associated with the measurement process and to the 2pi phase periodicity of the observation mechanism. In this paper, we formulate the wavefront reconstruction as an inverse problem, where the amplitude and the absolute phase are assumed to admit sparse linear representations in suitable sparsifying transforms (dictionaries). Sparse modeling is a form of regularization of inverse problems which, in the case of the absolute phase, is not available to the conventional wavefront reconstruction techniques, as only interferometric phase modulo-2pi is considered therein. The developed sparse modeling of the absolute phase solves two different problems: accuracy of the interferometric (wrapped) phase reconstruction and simultaneous phase unwrapping. Based on this rationale, we introduce the sparse phase and amplitude reconstruction (SPAR) algorithm. SPAR takes into full consideration the Poissonian (photon counting) measurements and uses the data-adaptive block matching 3D (BM3D) frames as a sparse representation for the amplitude and for the absolute phase. SPAR effectiveness is documented by comparing its performance with that of competitors in a series of experiments. PMID- 25121539 TI - Fast high-order perturbation of surfaces methods for simulation of multilayer plasmonic devices and metamaterials. AB - The scattering of time-harmonic linear waves by periodic media arises in a wide array of applications from materials science and nondestructive testing to remote sensing and oceanography. In this work we have in mind applications in optics, more specifically plasmonics, and the surface plasmon polaritons that are at the heart of remarkable phenomena such as extraordinary optical transmission, surface enhanced Raman scattering, and surface plasmon resonance biosensing. In this paper we develop robust, highly accurate, and extremely rapid numerical solvers for approximating solutions to grating scattering problems in the frequency regime where these are commonly used. For piecewise-constant dielectric constants, which are commonplace in these applications, surface formulations are clearly advantaged as they posit unknowns supported solely at the material interfaces. The algorithms we develop here are high-order perturbation of surfaces methods and generalize previous approaches to take advantage of the fact that these algorithms can be significantly accelerated when some or all of the interfaces are trivial (flat). More specifically, for configurations with one nontrivial interface (and one trivial interface) we describe an algorithm that has the same computational complexity as a two-layer solver. With numerical simulations and comparisons with experimental data, we demonstrate the speed, accuracy, and applicability of our new algorithms. PMID- 25121540 TI - Numerical solution of nonparaxial scalar diffraction integrals for focused fields. AB - In this paper, we present sampling conditions for fast-Fourier-transform-based field propagations. The input field and the propagation kernel are analyzed in a combined manner to derive sampling criteria that guarantee accurate calculation results in the output plane. These sampling criteria are also applicable to the propagation of general fields. For focal field calculations, geometrical optics is used to obtain a priori knowledge about the input and output fields. This a priori knowledge is used to determine an optimum balance between computational load and calculation accuracy. In a numerical example, correct results are obtained even though both the input field and the propagation kernel are sampled below the Nyquist rate. Finally, we show how chirp z-transform-based zoom algorithms may be analyzed using the same techniques. PMID- 25121541 TI - Large aperture adaptive doublet polymer lens for imaging applications. AB - We report a full design process-finite element modeling, fabrication, and characterization-of adaptive doublet polymer lenses. A first-order model was developed and used to design fluidic doublets, analogous to their glass counterparts. Two constant-volume fluidic chambers were enclosed by three flexible membranes, resulting in a variable focal length doublet with a clear aperture of 19.0 mm. Chromatic focal shift was then used to compare numerical modeling to experimentally measured results over a positive focal length range of 55-200 mm (f/2.89 to f/10.5). PMID- 25121542 TI - Compensation of modeling errors due to unknown domain boundary in diffuse optical tomography. AB - Diffuse optical tomography is a highly unstable problem with respect to modeling and measurement errors. During clinical measurements, the body shape is not always known, and an approximate model domain has to be employed. The use of an incorrect model domain can, however, lead to significant artifacts in the reconstructed images. Recently, the Bayesian approximation error theory has been proposed to handle model-based errors. In this work, the feasibility of the Bayesian approximation error approach to compensate for modeling errors due to unknown body shape is investigated. The approach is tested with simulations. The results show that the Bayesian approximation error method can be used to reduce artifacts in reconstructed images due to unknown domain shape. PMID- 25121543 TI - Plasmonic corrugated cylinder-cone terahertz probe. AB - The spoof surface plasmon polariton (SPP) effect on the electromagnetic field distribution near the tip of a periodically corrugated metal cylinder-cone probe working at the terahertz regime was studied. We found that radially polarized terahertz radiation could be coupled effectively through a spoof SPP into a surface wave and propagated along the corrugated surface, resulting in more than 20* electric field enhancement near the tip of probe. Multiple resonances caused by the antenna effect were discussed in detail by finite element computation and theoretical analysis of dispersion relation for spoof SPP modes. Moreover, the key figures of merit such as the resonance frequency of the SPP can be flexibly tuned by modifying the geometry of the probe structure, making it attractive for application in an apertureless background-free terahertz near-field microscope. PMID- 25121544 TI - Isochromatic lines as extension of Helmholtz reciprocity principle for effect paints. AB - Flake-based parameters were recently introduced as a physical concept to predict a series of measurement geometries producing similar reflection data for effect paints. We derive expressions to calculate these so-called isochromatic lines, connecting the two Helmholtz-reciprocal in-plane geometries with a series of out of-plane geometries. Thus isochromatic lines can be regarded as an extension of the Helmholtz reciprocity principle, which is valid for effect paints. We experimentally studied seven effect paint samples with large angular color variation along the length of four isochromatic lines. A change in illumination angles by up to 75 degrees while following isochromatic lines led to a standard deviation in color parameters of less than two units. When isochromatic lines were not followed, these colorimetric parameters varied by more than 10 units already by change in detection angle of 10 degrees . Therefore the concept of isochromatic lines works well for effect paints. PMID- 25121545 TI - Introducing the concept of anisotropy at different scales for modeling optical turbulence. AB - In this paper, the concept of anisotropy at different atmospheric turbulence scales is introduced. A power spectrum and its associated structure function with inner and outer scale effects and anisotropy are also shown. The power spectrum includes an effective anisotropic parameter zeta(eff) to describe anisotropy, which is useful for modeling optical turbulence when a non-Kolmogorov power law and anisotropy along the direction of propagation are present. PMID- 25121546 TI - DLAB: a class of daylight-based uniform color space. AB - CIELAB is based on the CIE 1931 color matching functions. If we are given a new set of color matching functions, how do we define a CIELAB-like uniform color space for the new functions? This problem arises because the CIE recommended its physiological cone fundamentals in 2006 and is considering a new set of color matching functions based on them. In fact, the same problem exists for many practical applications in digital imaging. Typical solutions involve using illuminant-dependent color correction matrices to transform the device-dependent color space into the CIE XYZ color space. This conversion process suffers information loss unless the two sets of color matching functions are linear combinations of each other. In this paper, we propose a design process that allows us to develop a CIELAB-like color space using the native sensor fundamentals. The basic idea is to choose the daylight locus as the yellow-blue opponent color process. We call this class of color space DLAB. We describe the design procedures and compare the resulting Munsell color uniformity under CIELAB (L*, a*, b*) and DLAB (L(+) ,a(+), b(+)). PMID- 25121547 TI - Fast reconstruction of fluorescence molecular tomography via a permissible region extraction strategy. AB - In order to obtain precise reconstruction results in fluorescence molecular tomography (FMT), large-scale matrix equations would be solved in the inverse problem generally. Thus, much time and memory needs to be consumed. In this paper, a permissible region extraction strategy is proposed to solve this problem. First, a preliminary result is rapidly reconstructed using the weight matrix compressed by principal component analysis or uniform sampling. And then the reconstructed target area in this preliminary result is considered as the a priori permissible region to guide the final reconstruction. Phantom experiments with double fluorescent targets are performed to test the performance of the strategy. The results illustrate that the proposed strategy can significantly accelerate the image reconstruction in FMT almost without quality degradation. PMID- 25121548 TI - Asymmetric information hiding and noise-free recovery based on rotating analyzer ellipsometry and quick-response code. AB - We report an asymmetric optical information hiding method based on a rotating analyzer ellipsometry technique. This asymmetric hiding architecture not only avoids the interception of keys during transmission or distribution but also makes the cyphertext more inconspicuous for attackers. A new kind of one-way optical trapdoor function is constructed based on the fact that the state of polarization (SOP) of elliptical polarized light cannot be recovered with only the knowledge of intensity captured after passing through a linear polarizer. Meanwhile, the SOP of a polarization ellipse could be calculated by rotating the polarizer to record two scenes of intensity after it. Introduction of a quick response code as a container leads to noise-free recovery for original information and enhances practicality of the proposed cryptosystem with versatile key sensitivity and fault tolerance capability. Numerical simulation results that support theoretical analysis are presented. Analysis on the relationship between hiding effect or quality of decryption and parameters of the algorithm also is provided. PMID- 25121551 TI - Diagnostic and prognostic TERT promoter mutations in thyroid fine-needle aspiration biopsy. AB - Two promoter mutations, chr5:1 295 228C>T and chr5:1 295 250C>T, in the gene for telomerase reverse transcriptase (TERT) have been recently identified in thyroid cancers and shown to be important in thyroid tumor pathogenesis. The diagnostic and prognostic potentials of testing for these mutations on thyroid fine-needle aspiration biopsy (FNAB) have not been investigated. Herein, we examined the two TERT promoter mutations along with the BRAF V600E mutation by direct DNA sequencing on 308 FNAB specimens preoperatively obtained from thyroid nodules with postoperatively confirmed pathological diagnoses. We found TERT promoter mutations in 0.0% (0/179) of benign thyroid nodules and 7.0% (9/129) of thyroid nodules of differentiated thyroid cancer, representing a 100% diagnostic specificity and 7.0% sensitivity, with the latter rising to 38.0% (49/129) when combined with BRAF V600E testing. Several TERT-promoter-mutation-positive thyroid nodules were cytologically indeterminate on FNAB. Approximately 80% of the TERT promoter mutation-positive thyroid nodules were thyroid cancers with aggressive clinicopathological behaviors, such as extrathyroidal invasion, lymph node metastases, distant metastases, disease recurrence or patient death. Thus, a positive TERT promoter mutation test not only definitively diagnoses a thyroid nodule as cancerous but also preoperatively identifies a cancer with aggressive potential. This is the first study, to our knowledge, of TERT promoter mutations on thyroid FNAB, demonstrating the value of this novel molecular testing in the diagnosis of thyroid nodules and preoperative risk stratification of thyroid cancer. Thus, testing of TERT promoter mutations on FNAB will enhance and improve the current molecular-based approaches to the management of thyroid nodules and thyroid cancer. PMID- 25121550 TI - Metagenomic identification of novel enteric viruses in urban wild rats and genome characterization of a group A rotavirus. AB - Rats are known as reservoirs and vectors for several zoonotic pathogens. However, information on the viruses shed by urban wild rats that could pose a zoonotic risk to human health is scare. Here, intestinal contents from 20 wild Norway rats (Rattus norvegicus) collected in the city of Berlin, Germany, were subjected to metagenomic analysis of viral nucleic acids. The determined faecal viromes of rats consisted of a variety of known and unknown viruses, and were highly variable among the individuals. Members of the families Parvoviridae and Picobirnaviridae represented the most abundant species. Novel picornaviruses, bocaviruses, sapoviruses and stool-associated circular ssDNA viruses were identified, which showed only low sequence identity to known representatives of the corresponding taxa. In addition, noroviruses and rotaviruses were detected as potential zoonotic gastroenteritis viruses. However, partial-genome sequence analyses indicated that the norovirus was closely related to the recently identified rat norovirus and the rotavirus B was closely related to the rat rotavirus strain IDIR; both viruses clustered separately from respective human virus strains in phylogenetic trees. In contrast, the rotavirus A sequences showed high identity to human and animal strains. Analysis of the nearly complete genome of this virus revealed the known genotypes G3, P[3] and N2 for three of the genome segments, whereas the remaining eight genome segments represented the novel genotypes I20-R11-C11-M10-A22-T14-E18-H13. Our results indicated a high heterogeneity of enteric viruses present in urban wild rats; their ability to be transmitted to humans remains to be assessed in the future. PMID- 25121549 TI - Novel porcine-like human G26P[19] rotavirus identified in hospitalized paediatric diarrhoea patients in Ho Chi Minh City, Vietnam. AB - During a hospital-based diarrhoeal disease study conducted in Ho Chi Minh City, Vietnam from 2009 to 2010, we identified four symptomatic children infected with G26P[19] rotavirus (RV)--an atypical variant that has not previously been reported in human gastroenteritis. To determine the genetic structure and investigate the origin of this G26P[19] strain, the whole genome of a representative example was characterized, revealing a novel genome constellation: G26-P[19]-I5-R1-C1-M1-A8-N1-T1-E1-H1. The genome segments were most closely related to porcine (VP7, VP4, VP6 and NSP1) and Wa-like porcine RVs (VP1-3 and NSP2-5). We proposed that this G26P[19] strain was the product of zoonotic transmission coupled with one or more reassortment events occurring in human and/or animal reservoirs. The identification of such strains has potential implications for vaccine efficacy in south-east Asia, and outlines the utility of whole-genome sequencing for studying RV diversity and zoonotic potential during disease surveillance. PMID- 25121553 TI - Two human challenge studies confirm high infectivity of Norwalk virus. PMID- 25121554 TI - Yeast as a potential vehicle for neglected tropical disease drug discovery. AB - High-throughput screening (HTS) efforts for neglected tropical disease (NTD) drug discovery have recently received increased attention because several initiatives have begun to attempt to reduce the deficit in new and clinically acceptable therapies for this spectrum of infectious diseases. HTS primarily uses two basic approaches, cell-based and in vitro target-directed screening. Both of these approaches have problems; for example, cell-based screening does not reveal the target or targets that are hit, whereas in vitro methodologies lack a cellular context. Furthermore, both can be technically challenging, expensive, and difficult to miniaturize for ultra-HTS [(u)HTS]. The application of yeast-based systems may overcome some of these problems and offer a cost-effective platform for target-directed screening within a eukaryotic cell context. Here, we review the advantages and limitations of the technologies that may be used in yeast cell based, target-directed screening protocols, and we discuss how these are beginning to be used in NTD drug discovery. PMID- 25121552 TI - Enalapril and ASS inhibit tumor growth in a transgenic mouse model of islet cell tumors. AB - Accumulating evidence suggests a role for angiotensin-converting enzymes involving the angiotensin II-receptor 1 (AT1-R) and the cyclooxygenase pathway in carcinogenesis. The effects of ASS and enalapril were assessed in vitro and in a transgenic mouse model of pancreatic neuroendocrine neoplasms (pNENs). The effects of enalapril and ASS on proliferation and expression of the AGTR1A and its target gene vascular endothelial growth factor (Vegfa) were assessed in the neuroendocrine cell line BON1. Rip1-Tag2 mice were treated daily with either 0.6 mg/kg bodyweight of enalapril i.p., 20 mg/kg bodyweight of ASS i.p., or a vehicle in a prevention (weeks 5-12) and a survival group (week 5 till death). Tumor surface, weight of pancreatic glands, immunostaining for AT1-R and nuclear factor kappa beta (NFKB), and mice survival were analyzed. In addition, sections from human specimens of 20 insulinomas, ten gastrinomas, and 12 non-functional pNENs were evaluated for AT1-R and NFKB (NFKB1) expression and grouped according to the current WHO classification. Proliferation was significantly inhibited by enalapril and ASS in BON1 cells, with the combination being the most effective. Treatment with enalapril and ASS led to significant downregulation of known target genes Vegf and Rela at RNA level. Tumor growth was significantly inhibited by enalapril and ASS in the prevention group displayed by a reduction of tumor size (84%/67%) and number (30%/45%). Furthermore, daily treatment with enalapril and ASS prolonged the overall median survival compared with vehicle-treated Rip1 Tag2 (107 days) mice by 9 and 17 days (P=0.016 and P=0.013). The AT1-R and the inflammatory transcription factor NFKB were abolished completely upon enalapril and ASS treatment. AT1-R and NFKB expressions were observed in 80% of human pNENs. Enalapril and ASS may provide an approach for chemoprevention and treatment of pNENs. PMID- 25121555 TI - Discovery of new uncompetitive inhibitors of glucose-6-phosphate dehydrogenase. AB - The enzyme glucose-6-phosphate dehydrogenase (G6PDH) catalyzes the first step of the oxidative branch of the pentose phosphate pathway, which provides cells with NADPH, an essential cofactor for many biosynthetic pathways and antioxidizing enzymes. In Trypanosoma cruzi, the G6PDH has being pursued as a relevant target for the development of new drugs against Chagas disease. At present, the best characterized inhibitors of T. cruzi G6PDH are steroidal halogenated compounds derivatives from the mammalian hormone precursor dehydroepiandrosterone, which indeed are also good inhibitors of the human homologue enzyme. The lack of target selectivity might result in hemolytic side effects due to partial inhibition of human G6PDH in red blood cells. Moreover, the treatment of Chagas patients with steroidal drugs might also cause undesired androgenic side effects. Aiming to identify of new chemical classes of T. cruzi G6PDH inhibitors, we performed a target-based high-throughput screen campaign against a commercial library of diverse compounds. Novel TcG6PDH inhibitors were identified among thienopyrimidine and quinazolinone derivatives. Preliminary structure activity relationships for the identified hits are presented, including structural features that contribute for selectivity toward the parasite enzyme. Our results indicate that quinazolinones are promising hits that should be considered for further optimization. PMID- 25121556 TI - A CXCR1 haplotype hampers HIV-1 matrix protein p17 biological activity. AB - OBJECTIVE: Monocyte inflammatory processes are fundamental events in AIDS pathogenesis. HIV-1 matrix protein p17, released from infected cells, was found to exert an interleukin (IL)-8 chemokine-like activity on human monocytes, promoting their trafficking and sustaining inflammatory processes, after binding to CXCR1. A haplotype of the CXCR1 gene (CXCR1_300_142) has been associated with slow HIV disease progression. Here, we determine how CXCR1 genetic variations impact on p17 biological activity. DESIGN/METHODS/RESULTS: Our results show that Jurkat cells overexpressing CXCR1 or the receptor carrying single polymorphism CXCR1_300 or CXCR1_142 are able to adhere and migrate in response to both IL-8 and p17. On the contrary, Jurkat cells overexpressing CXCR1_300_142 and monocytes of individuals with such CXCR1 polymorphisms lose the capacity to adhere and migrate in response to p17, but not to their physiological ligand IL-8. Surface plasmon resonance (SPR) and multispectral imaging flow cytometry showed that p17 bound with similar affinity to CXCR1 and CXCR1_300_142. Moreover, whereas p17 was able to activate CXCR1, it was incapable of functionally interacting with CXCR1_300_142 by phosphorylating extracellular signal-regulated kinase 1/2, which regulates chemokine-induced cellular responses. Finally, mutagenesis studies showed that, unlike IL-8, p17 does not use Glu-Leu-Arg-like motifs to activate CXCR1. CONCLUSIONS: Our results, showing the inability of p17 to activate CXCR1_300_142, a receptor found to be expressed on immune cells of patients with a low progression of HIV disease, point to a crucial role of p17 in AIDS pathogenesis. Our findings herein call for an exploration of the therapeutic potential of blocking the p17/CXCR1 axis in HIV infection. PMID- 25121558 TI - Erratum to: Effects of Saccharomyces boulardii on Neonatal Hyperbilirubinemia: A Randomized Controlled Trial. PMID- 25121557 TI - Hydrogen preconditioning during ex vivo lung perfusion improves the quality of lung grafts in rats. AB - BACKGROUND: Although the benefits of ex vivo lung perfusion (EVLP) have been globally advocated, the potentially deleterious effects of applying EVLP, in particular activation of proinflammatory cascades and alteration of metabolic profiles, are rarely discussed. This study examined proinflammatory events and metabolic profiles in lung grafts on EVLP and tested whether preconditioning lung grafts with inhaled hydrogen, a potent, cytoprotective gaseous signaling molecule, would alter the lungs' response to EVLP. METHODS: Rat heart-lung blocks were mounted on an acellular normothermic EVLP system for 4 hr and ventilated with air or air supplemented with 2% hydrogen. Arterial and airway pressures were monitored continuously; perfusate was sampled hourly to examine oxygenation. After EVLP, the lung grafts were transplanted orthotopically into syngeneic rats, and lung function was examined. RESULTS: Placing lung grafts on EVLP resulted in significant upregulation of the messenger RNAs for several proinflammatory cytokines, higher glucose consumption, and increased lactate production. Hydrogen administration attenuated proinflammatory changes during EVLP through upregulation of the heme oxygenase-1. Hydrogen administration also promoted mitochondrial biogenesis and significantly decreased lactate production. Additionally, in the hydrogen-treated lungs, the expression of hypoxia-inducible factor-1 was significantly attenuated during EVLP. These effects were maintained throughout EVLP and led to better posttransplant lung graft function in the recipients of hydrogen-treated lungs. CONCLUSIONS: Lung grafts on EVLP exhibited prominent proinflammatory changes and compromised metabolic profiles. Preconditioning lung grafts using inhaled hydrogen attenuated these proinflammatory changes, promoted mitochondrial biogenesis in the lungs throughout the procedure, and resulted in better posttransplant graft function. PMID- 25121559 TI - Stewart-Bluefarb syndrome: Report of five cases and a review of literature. AB - Stewart-Bluefarb syndrome is a rare angioproliferative disorder characterised by acroangiodermatitis associated with an underlying arteriovenous shunt. This condition should be differentiated from acroangiodermatitis of Mali classically described in association with chronic venous insufficiency. Patients with Stewart Bluefarb syndrome typically present with lower leg pigmented macules, papules and plaques that can coalesce to form larger confluent patches of pigmentation. Recognition of Stewart-Bluefarb syndrome may be difficult or delayed as the cutaneous manifestations may resemble a variety of other dermatological conditions. Most commonly, acroangiodermatitis may be confused with Kaposi's sarcoma and the condition is often referred to as 'Pseudo-Kaposi's sarcoma'. Acroangiodermatitis may also resemble or coexist with pigmentation of chronic venous insufficiency. As seen in this report, acroangiodermatitis may also be clinically confused with the 'cavernous' form of a capillary malformation. Here, we describe five patients with Stewart-Bluefarb syndrome. In one female and two male patients the diagnosis was delayed as the acroangiodermatitis closely resembled other conditions. All underlying arterio-venous communications were initially diagnosed on duplex ultrasound and confirmed with magnetic resonance angiography. Four patients were found to have a congenital arterio-venous malformation while one was diagnosed with a post-thrombotic arterio-venous fistula. Management included observation and intervention using a variety of techniques including percutaneous or trans-catheter embolisation, endovenous laser, radiofrequency ablation and foam ultrasound guided sclerotherapy. This case series highlights the challenges involved in the diagnosis and management of Stewart-Bluefarb syndrome. Given the local and systemic sequelae of high flow shunts, correct diagnosis and early detection of the underlying arterio-venous abnormality is crucial in the long-term management of these patients and in preventing the associated complications. PMID- 25121560 TI - Regional differences in statistical geometry of endothelial dense granules in human extremity veins. AB - OBJECTIVES: Leg and arm human veins are exposed to different gravitational stresses. We investigated if there is difference in the amount and geometry of secretory vesicles in their endothelium. METHODS: Superficial small vein segments were removed during vascular operations for electromicroscopic analysis. Vesicular area/total endothelial cross-sectional area was determined by computer based morphometry. Long and short axes of granule cross sections were measured by image analyzing software. RESULTS: Vesicular density in all samples was 2.26 +/- 0.34%. There was no significant difference between the vesicular densities of upper extremity and leg. The shape of the vesicles was more frequently elongated in leg than in arm sections (p < 0.01). CONCLUSIONS: The density of the vesicles does not depend on vascular region or orthostatic load. Ellipticity of these granules is significantly different in areas exposed to different gravitational stresses. This might contribute to the differences of thrombotic and hemodynamic properties of leg and upper body veins. PMID- 25121561 TI - Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer. AB - BACKGROUND: Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is effective in reducing serum uric acid, the build-up of which causes TLS. It is uncertain whether high-quality evidence exists to support its routine use in children with malignancies. OBJECTIVES: To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies. SEARCH METHODS: This is an update of the original review. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library issue 1, 2013), MEDLINE (1966 to February 2013), Embase (1980 to February 2013), and CINAHL (1982 to February 2013). In addition, we searched the reference lists of all identified relevant papers. We also explored other internet sources (updated search on 26 February 2013): the NHS' National Research Register, the US National Institutes of Health Ongoing Trials Register, the metaRegister of Controlled Trials, and ProQuest Dissertations & Theses Database. We also screened conference proceedings of the American Society of Clinical Oncology, the European Society for Medical Oncology, and the International Society of Paediatric Oncology meetings from 1993 to 2012. Finally, we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis. SELECTION CRITERIA: Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data. MAIN RESULTS: We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT showed no significant difference in mortality (both all cause mortality and mortality due to TLS), renal failure, and adverse effects between the treatment and the control groups. The frequency of normalisation of uric acid at four hours (Fisher's exact test P < 0.001) and area under curve of uric acid at four days (MD -201.00 mg/dLhr, 95% confidence interval (CI) -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group. The trial did not evaluate the primary outcome (incidence of clinical TLS).Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); all cause mortality was not significantly different between the groups. Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs), three days (two CCTs), four days (two CCTs), and seven days (one CCT) after therapy, but not one day (three CCTs), five days (one CCT), and 12 days (one CCT) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03). One CCT evaluated the primary outcome; no significant difference was identified.Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated no significant difference in uric acid normalisation and uric acid level at four hours). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no significant difference between treatment groups was identified. No significant difference in mortality (all cause mortality and mortality due to TLS) and renal failure was identified. The primary outcome was not evaluated.All included trials were highly susceptible to biases. AUTHORS' CONCLUSIONS: Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical tumour lysis syndrome, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects. PMID- 25121562 TI - Predictors of postpartum depression. AB - OBJECTIVE: To examine sociodemographic factors, pregnancy-associated psychosocial stress and depression, health risk behaviors, prepregnancy medical and psychiatric illness, pregnancy-related illnesses, and birth outcomes as risk factors for post-partum depression (PPD). METHODS: A prospective cohort study screened women at 4 and 8 months of pregnancy and used hierarchical logistic regression analyses to examine predictors of PPD. The study sample include 1,423 pregnant women at a university-based high risk obstetrics clinic. A score of >=10 on the Patient Health Questionnaire-9 (PHQ-9) indicated clinically significant depressive symptoms. RESULTS: Compared with women without significant postpartum depressive symptoms, women with PPD were significantly younger (p<0.0001), more likely to be unemployed (p=0.04), had more pregnancy associated depressive symptoms (p<0.0001) and psychosocial stress (p<0.0001), were more likely to be smokers (p<0.0001), were more likely to be taking antidepressants (ADs) during pregnancy (p=0.002), were less likely to drink any alcohol during pregnancy (p=0.02), and were more likely to have prepregnancy medical illnesses, including diabetes (p=0.02) and neurologic conditions (p=0.02). CONCLUSION: Specific sociodemographic and clinical risk factors for PPD were identified that could help physicians target depression case finding for pregnant women. PMID- 25121563 TI - Azithromycin associated with a reduction in 90-day mortality among older pneumonia patients, although a true clinical benefit is uncertain. PMID- 25121564 TI - Peer review of human studies run amok: a break in the fiduciary relation between scientists and the public. AB - Peer review aims to ensure the quality and credibility of research reporting. Conducted by volunteer scientists who receive no guidance or direction, peer review widely varies from fast and facilitative, to unclear and obstructive. Poor quality is an issue because most science research is publicly funded, whereby scientists must make an effort to quickly disseminate their findings back to the public. An unfortunately not uncommon barrier in this process is ineffective peer review. Most scientists agree that when done well, editors and reviewers drive and maintain the high standards of science. At the same time, ineffective peer review can cause great delay with no introduced improvement in final product. These delays and requests interfere with the path of communication between scientist and public, at a great cost to editors, reviewers, authors and those who stand to benefit from application of the results of the studies. We offer a series of concrete recommendations to improve this process. PMID- 25121565 TI - Balancing competing risks: perinatal exposure to macrolides increases the risk of infantile hypertrophic pyloric stenosis. PMID- 25121566 TI - Computational models on quantitative prediction of bioactivity of HIV-1 integrase 3' processing inhibitors. AB - In this study, four computational quantitative structure-activity relationship (QSAR) models were built to predict the bioactivity of 3' processing (3'P) inhibitors of HIV-1 integrase. Some 453 inhibitors whose bioactivity values were detected by the radiolabelling method were collected. The molecular structures were represented with MOE descriptors. In total, 21 descriptors were selected for modelling. All inhibitors were divided into a training set and a test set with two methods: (1) by a Kohonen's self-organizing map (SOM); (2) by a random selection. For every training set and test set, a multilinear regression (MLR) analysis and a support vector machine (SVM) were used to establish models, respectively. For the training/test set divided by SOM, the correlation coefficients (r) were over 0.84, and for the training/test set split randomly, the r values were over 0.86. Some molecular properties such as hydrogen bond donor capacity, atomic partial charge properties, molecular refractivity, the number of aromatic bonds and molecular surface area, volume and shape properties played important roles for inhibiting 3' processing step of HIV-1 integrase. PMID- 25121567 TI - Effect of unawareness on rehabilitation outcome in a randomised controlled trial of multicomponent intervention for patients with mild Alzheimer's disease. AB - Unawareness of deficit has been shown to affect the outcome of targeted cognitive intervention programmes applied to patients with Alzheimer' disease (AD), but the effects on multimodal therapeutic approaches have not yet been explored. This research investigated the efficacy of the Multi-Intervention Programme (MIP) approach on improving cognitive, functional, affective, and behavioural symptoms in people with mild AD. In addition, we examined whether the presence of unawareness influences the MIP outcomes. Sixty-one mild stage AD patients were randomly assigned to either an experimental group which carried out an MIP individually (48 sessions, 16 weeks duration), combining diverse cognitive tasks, training in daily life and recreational activities, or a waiting list group which did not receive any treatment for the same time period. The efficacy of MIP (vs. waiting list) was tested using various standardised neuropsychological, functional, and behavioural outcome measures. Planned analyses were carried out to determine the effect of unawareness versus awareness on such outcomes. The results showed that patients overall benefited from the MIP in terms of both cognitive and non-cognitive symptoms. AD patients with awareness of deficits showed positive effects on all outcome measures in comparison with the waiting list group, while AD patients with unawareness showed improvements in non cognitive symptoms only. In conclusion, the presence of unawareness reduces the cognitive and functional effects of MIP in patients with mild AD. PMID- 25121568 TI - A quantitative investigation of hemodynamic adaptation to pregnancy using uterine artery Doppler ultrasonography and finger photoplethysmography. AB - OBJECTIVE: Normal pregnancy is characterized by maternal hemodynamic adaptations of cardiovascular system and uterine artery. We aimed to investigate quantitatively the relationship between uterine artery Doppler (Ut AD) ultrasonography and finger photoplethysmography (PPG) in each of the three trimesters. METHODS: Eighty normal pregnancy subjects were recruited from the nulliparous women with uncomplicated singleton pregnancy presenting for a routine ultrasound scan and divided into three groups according to their trimester. Comparative analysis were conducted between Ut AD ultrasonography and finger PPG within and across trimesters, particularly with focus on the relationship between Uterine Artery Resistance Index (UtA RI) and photoplethysmographic reflection index (PPG RI) throughout pregnancy. Additional 10 preeclampsia patients in third trimester were enrolled for comparison. RESULTS: Both UtA RI and PPG RI were markedly decreased with gestation in normal pregnancy and generally consistent with each other in trend. The preeclampsia patients of third trimester were significantly higher in both indices, even more than normal pregnancy subjects of first trimester. CONCLUSIONS: The results of this study revealed clear relationship between UtA RI and PPG RI throughout pregnancy which could be exploited to enhance the potential ability in early recognition of pathophysiologic process in maternal adaptation and prediction of complicated pregnancy. PMID- 25121569 TI - Target temperature management for postcardiac arrest patients. PMID- 25121571 TI - Cortical thickness in ALS: towards a marker for upper motor neuron involvement. AB - OBJECTIVE: Examine whether cortical thinning is a disease-specific phenomenon across the spectrum of motor neuron diseases in relation to upper motor neuron (UMN) involvement. METHODS: 153 patients (112 amyotrophic lateral sclerosis (ALS), 19 patients with a clinical UMN phenotype, 22 with a lower motor neuron (LMN) phenotype), 60 healthy controls and 43 patients with an ALS mimic disorder were included for a cross-sectional cortical thickness analysis. Thirty-nine patients with ALS underwent a follow-up scan. T1-weighted images of the brain were acquired using a 3 T scanner. The relation between cortical thickness and clinical measures, and the longitudinal changes were examined. RESULTS: Cortical thickness of the precentral gyrus (PCG) was significantly reduced in ALS (p=1.71*10(-13)) but not in mimic disorders (p=0.37) or patients with an LMN phenotype (p=0.37), as compared to the group of healthy controls. Compared to patients with ALS, patients with a UMN phenotype showed an even lower PCG cortical thickness (p=1.97*10(-3)). Bulbar scores and arm functional scores showed a significant association with cortical thickness of corresponding body regions of the motor homunculus. Longitudinal analysis revealed a decrease of cortical thickness in the left temporal lobe of patients with ALS (parahippocampal region p=0.007 and fusiform cortex p=0.001). CONCLUSIONS: PCG cortical thinning was found to be specific for motor neuron disease with clinical UMN involvement. Normal levels of cortical thickness in mimic disorders or LMN phenotypes suggest that cortical thinning reflects pathological changes related to UMN involvement. Progressive cortical thinning in the temporal lobe suggests recruitment of non-motor areas, over time. PMID- 25121572 TI - CSF lactate levels, tau proteins, cognitive decline: a dynamic relationship in Alzheimer's disease. AB - OBJECTIVES: To investigate, in patients with Alzheimer's Disease (AD), the possible interplay linking alteration of neuronal energy metabolism, as measured via cerebrospinal fluid (CSF) lactate concentration, to severity of AD neurodegenerative processes and impairment of cognitive abilities. METHODS: In this study we measured and correlated CSF lactate concentrations, AD biomarker levels (tau-proteins and beta-amyloid) and Mini-Mental State Examination (MMSE) score in a population of drug-naive patients with AD ranging from mild (MMSE>=21/30) to moderate-severe (MMSE<21/30) cognitive decline. They were compared to healthy controls and patients with vascular dementia (VaD). RESULTS: Patients with AD (n=145) showed a significant increase of CSF lactate concentration compared to controls (n=80) and patients with VaD (n=44), which was higher in mild (n=67) than in patients with moderate-severe AD (n=78). Moreover, we found, in either the whole AD population or both subgroups, a CSF profile in which higher CSF levels of t-tau and p-tau proteins corresponded to lower concentrations of lactate. CONCLUSIONS: We verified the occurrence of high CSF lactate levels in patients with AD, which may be ascribed to mitochondria impairment. Hypothesising that tau proteins may exert a detrimental effect on the entire cellular energy metabolism, the negative correlation found between lactate and tau-protein levels may allow speculation that tau toxicity, already demonstrated to have affected mitochondria, could also impair glycolytic metabolism with a less evident increase of lactate levels in more severe AD. Thus, we suggest a dynamic relationship between neuronal energy metabolism, tau proteins and cognitive decline in AD and propose the clinical potential of assessing CSF lactate levels in patients with AD to better define the neuronal brain metabolism damage. PMID- 25121573 TI - Survey of common practices among oculofacial surgeons in the Asia-Pacific region: Graves' orbitopathy. AB - AIM: A web-based anonymous survey was performed to evaluate practice preferences in the management of Graves' orbitopathy amongst oculofacial surgeons in the Asia Pacific region. METHODS: A questionnaire with contentious topics in Graves' orbitopathy was sent out via email to oculofacial surgeons in 14 countries within Asia-Pacific between May to December 2012. RESULTS: A response rate of 25.2% to 34.6% was achieved (32-44 of 127 participants). 61.0% of respondents encountered Graves' orbitopathy commonly in their practice. The more common causes of vision loss in Graves' orbitopathy included dysthyroid optic neuropathy (67.5%) and exposure keratopathy (15.0%). The clinical activity score was the most popular grading system for assessing Graves' orbitopathy. The preferred non-surgical therapeutic approaches included intravenous pulsed methylprednisolone (79.5%), oral steroids (56.4%), orbital radiation (12.8%), steroid-sparing immunosuppressants (10.3%) and watchful observation (7.7%). Thyroid orbital decompression was uncommonly or rarely performed by respondents. Orbital surgical decompression was most commonly performed via the two-wall technique (73.5%) and most respondents performed fat decompression (69.4%). Post-operatively, the most common complications include under correction (45.5%) and diplopia (42.4%). CONCLUSION: We report the results of the first survey on the management of Graves' orbitopathy amongst oculofacial surgeons in Asia-Pacific. Our respondents practice preferences reflected the Graves' orbitopathy management consensus statement by the European group on Graves' orbitopathy in 2008. PMID- 25121570 TI - Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. AB - BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibodies have been recently described in children with acute disseminating encephalomyelitis (ADEM), but the clinical and neuroradiological characterisation of this subgroup is lacking. OBJECTIVE: To compare the clinical and neuroradiological features of paediatric ADEM with and without MOG antibodies. METHODS: Clinical course, cerebrospinal fluid (CSF)-, MRI studies, outcome and MOG status of 33 paediatric ADEM prospectively studied were reviewed. RESULTS: MOG antibodies (median 1:2560; range 1:160-1:20 480) were detected in 19 children with ADEM. The majority of children showed a decline of serum MOG-IgG titres over time. Children with MOG antibodies did not differ in their age at presentation, sex ratio, the presence of oligoclonal bands, clinical symptoms or initial severity, apart from a higher CSF cell count (p=0.038), compared with children without MOG antibodies. In addition, further relapsing demyelinating episodes associated with MOG antibodies were observed only in children with MOG antibodies. All 19 children with MOG antibodies had a uniform MRI pattern, characterised by large, hazy and bilateral lesions and the absence of atypical MRI features (eg, mainly small lesions, well defined lesions), which was significantly different compared to that of children without MOG antibodies (p=0.003; and p=0.032, respectively). In addition, children with MOG antibodies had involvement of more anatomical areas (p=0.035) including the myelon characterised by a longitudinally extensive transverse myelitis (p=0.003), more often a complete resolution of lesions (p=0.036) and a better outcome (p=0.038). CONCLUSIONS: Patients with ADEM with MOG antibodies in our cohort had a uniform MRI characterised by large, bilateral and widespread lesions with an increased frequency of longitudinal extensive transverse myelitis and a favourable clinical outcome in contrast to children lacking MOG antibodies. PMID- 25121574 TI - Formation of bare UO2(2+) and NUO(+) by fragmentation of gas-phase uranyl acetonitrile complexes. AB - In a prior study [Van Stipdonk; et al. J. Phys. Chem. A 2006, 110, 959-970], electrospray ionization (ESI) was used to generate doubly charged complex ions composed of the uranyl ion and acetonitrile (acn) ligands. The complexes, general formula [UO2(acn)n](2+), n = 0-5, were isolated in an 3-D quadrupole ion-trap mass spectrometer to probe intrinsic reactions with H2O. Two general reaction pathways were observed: (a) the direct addition of one or more H2O ligands to the doubly charged complexes and (b) charge-exchange reactions. For the former, the intrinsic tendency to add H2O was dependent on the number and type of nitrile ligand. For the latter, charge exchange involved primarily the formation of uranyl hydroxide, [UO2OH](+), presumably via a collision with gas-phase H2O and the elimination of a protonated nitrile ligand. Examination of general ion fragmentation patterns by collision-induced dissociation, however, was hindered by the pronounced tendency to generate hydrated species. In an update to this story, we have revisited the fragmentation of uranyl-acetonitrile complexes in a linear ion-trap (LIT) mass spectrometer. Lower partial pressures of adventitious H2O in the LIT (compared to the 3-D ion trap used in our previous study) minimized adduct formation and allowed access to lower uranyl coordination numbers than previously possible. We have now been able to investigate the fragmentation behavior of these complex ions completely, with a focus on tendency to undergo ligand elimination versus charge reduction reactions. CID can be used to drive ligand elimination to completion to furnish the bare uranyl dication, UO2(2+). In addition, fragmentation of [UO2(acn)](2+) generated [UO2(NC)](+), which subsequently fragmented to furnish NUO(+). Formation of the nitrido by transfer of N from cyanide was confirmed using precursors labeled with (15)N. The observed formation of [UO2(NC)](+) and NUO(+) was modeled by density functional theory. PMID- 25121578 TI - Evidence of water-in-ionic liquid microemulsion formation by nonionic surfactant Brij-35. AB - Brij-35, a common and popular nonionic surfactant, is shown to form water-in ionic liquid (w/IL) microemulsions with IL 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) as the bulk phase. The presence of w/[bmim][PF6] microemulsions is hinted by the significantly increased solubility of water in Brij-35 solution of [bmim][PF6]. The formation of w/[bmim][PF6] microemulsions by Brij-35 is confirmed using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) measurements. Brij-35 forms reverse micelle type aggregates within [bmim][PF6] in the absence of added-water. These reverse micelles become w/[bmim][PF6] microemulsions as the water is added to the system. As the water loading (w0) is increased, the average diameter of the aggregates increases. Fourier transform infrared (FTIR) absorbance data reveal the presence of both "bound" and "free" water within the system. The "bound" water is associated with the water pools of the w/[bmim][PF6] microemulsions. Excited state proton transfer (ESPT) involving probe pyranine shows deprotonation of pyranine within the water pools of the w/[bmim][PF6] microemulsions. PMID- 25121576 TI - Photochemical tyrosine oxidation in the structurally well-defined alpha3Y protein: proton-coupled electron transfer and a long-lived tyrosine radical. AB - Tyrosine oxidation-reduction involves proton-coupled electron transfer (PCET) and a reactive radical state. These properties are effectively controlled in enzymes that use tyrosine as a high-potential, one-electron redox cofactor. The alpha3Y model protein contains Y32, which can be reversibly oxidized and reduced in voltammetry measurements. Structural and kinetic properties of alpha3Y are presented. A solution NMR structural analysis reveals that Y32 is the most deeply buried residue in alpha3Y. Time-resolved spectroscopy using a soluble flash quench generated [Ru(2,2'-bipyridine)3](3+) oxidant provides high-quality Y32-O* absorption spectra. The rate constant of Y32 oxidation (kPCET) is pH dependent: 1.4 * 10(4) M(-1) s(-1) (pH 5.5), 1.8 * 10(5) M(-1) s(-1) (pH 8.5), 5.4 * 10(3) M(-1) s(-1) (pD 5.5), and 4.0 * 10(4) M(-1) s(-1) (pD 8.5). k(H)/k(D) of Y32 oxidation is 2.5 +/- 0.5 and 4.5 +/- 0.9 at pH(D) 5.5 and 8.5, respectively. These pH and isotope characteristics suggest a concerted or stepwise, proton first Y32 oxidation mechanism. The photochemical yield of Y32-O* is 28-58% versus the concentration of [Ru(2,2'-bipyridine)3](3+). Y32-O* decays slowly, t1/2 in the range of 2-10 s, at both pH 5.5 and 8.5, via radical-radical dimerization as shown by second-order kinetics and fluorescence data. The high stability of Y32 O* is discussed relative to the structural properties of the Y32 site. Finally, the static alpha3Y NMR structure cannot explain (i) how the phenolic proton released upon oxidation is removed or (ii) how two Y32-O* come together to form dityrosine. These observations suggest that the dynamic properties of the protein ensemble may play an essential role in controlling the PCET and radical decay characteristics of alpha3Y. PMID- 25121579 TI - Palladium-catalyzed intramolecular oxidative coupling involving double C(sp(2))-H bonds for the synthesis of annulated biaryl sultams. AB - The palladium-catalyzed intramolecular oxidative coupling described herein involves a double C(sp(2))-H bond functionalization in sulfonanilides, providing a workable access to biaryl sultams annulated into a six-membered ring that are otherwise difficult to obtain by literature methods. The other synthetic applications of this protocol including the synthesis of biaryl sultams containing a seven-membered ring and analogous sultones are also presented. PMID- 25121577 TI - Reduction-sensitive dual functional nanomicelles for improved delivery of paclitaxel. AB - We have developed a dual-functional nanocarrier composed of a hydrophilic polyethylene glycol (PEG) and a hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist), which is effective in delivery of hydrophobic anticancer drug, paclitaxel (PTX). To facilitate the retention of the therapeutic activity of the carrier, FTS was coupled to PEG via a reduction-sensitive disulfide linkage (PEG5k-S-S-FTS2). PEG5k-S-S-FTS2 conjugate formed uniform micelles with very small size (~30 nm) and the hydrophobic drug PTX could be readily incorporated into the micelles. Interestingly, inclusion of a disulfide linkage into the PEG5k-FTS2 micellar system resulted in a 4-fold decrease in the critical micelle concentration (CMC). In addition, the PTX loading capacity and colloidal stability of PTX-loaded micelles were improved. HPLC-MS showed that parent FTS could be more effectively released from PEG5k-S-S-FTS2 conjugate in tumor cells/tissues compared to PEG5k-FTS2 conjugate in vitro and in vivo. PEG5k S-S-FTS2 exhibited a higher level of cytotoxicity toward tumor cells than PEG5k FTS2 without a disulfide linkage. Furthermore, PTX-loaded PEG5k-S-S-FTS2 micelles were more effective in inhibiting the proliferation of cultured tumor cells compared to Taxol and PTX loaded in PEG5k-FTS2 micelles. More importantly, PTX loaded PEG5k-S-S-FTS2 micelles demonstrated superior antitumor activity compared to Taxol and PTX formulated in PEG5k-FTS2 micelles in an aggressive murine breast cancer model (4T1.2). PMID- 25121580 TI - Loop-Closure and Gaussian Models of Collective Structural Characteristics of Capped PEO Oligomers in Water. AB - Parallel-tempering MD results for a CH3(CH2-O-CH2)mCH3 chain in water are exploited as a database for analysis of collective structural characteristics of the PEO globule with a goal of defining models permitting statistical thermodynamic analysis of dispersants of Corexit type. The chain structure factor, relevant to neutron scattering from a deuterated chain in null water, is considered specifically. The traditional continuum-Gaussian structure factor is inconsistent with the simple k -> infinity behavior, but we consider a discrete Gaussian model that does achieve that consistency. Shifting and scaling the discrete-Gaussian model helps to identify the low-k to high-k transition near k ~ 2pi/0.6 nm when an empirically matched number of Gaussian links is about one third of the total number of effective atom sites. This short distance-scale boundary of 0.6 nm is directly verified with the r space distributions, and this distance is thus identified with a natural size for coarsened monomers. The probability distribution of Rg(2) is compared with the classic predictions for both the Gaussian model and freely jointed chains. ?Rg(2)(j)?, the contribution of the jth chain segment to ?Rg(2)?, depends on the contour index about as expected for Gaussian chains despite significant quantitative discrepancies that express the swelling of these chains in water. Monomers central to the chain contour occupy the center of the chain globule. The density profiles of chain segments relative to their center of mass can show distinctive density structuring for smaller chains due to the close proximity of central elements to the globule center. However, that density structuring washes out for longer chains where many chain elements additively contribute to the density profiles. Gaussian chain models thus become more satisfactory for the density profiles for longer chains. PMID- 25121581 TI - Order reduction of the chemical master equation via balanced realisation. AB - We consider a Markov process in continuous time with a finite number of discrete states. The time-dependent probabilities of being in any state of the Markov chain are governed by a set of ordinary differential equations, whose dimension might be large even for trivial systems. Here, we derive a reduced ODE set that accurately approximates the probabilities of subspaces of interest with a known error bound. Our methodology is based on model reduction by balanced truncation and can be considerably more computationally efficient than solving the chemical master equation directly. We show the applicability of our method by analysing stochastic chemical reactions. First, we obtain a reduced order model for the infinitesimal generator of a Markov chain that models a reversible, monomolecular reaction. Later, we obtain a reduced order model for a catalytic conversion of substrate to a product (a so-called Michaelis-Menten mechanism), and compare its dynamics with a rapid equilibrium approximation method. For this example, we highlight the savings on the computational load obtained by means of the reduced order model. Furthermore, we revisit the substrate catalytic conversion by obtaining a lower-order model that approximates the probability of having predefined ranges of product molecules. In such an example, we obtain an approximation of the output of a model with 5151 states by a reduced model with 16 states. Finally, we obtain a reduced-order model of the Brusselator. PMID- 25121582 TI - Neglected tropical diseases: a systematic evaluation of research capacity in Nigeria. AB - BACKGROUND: Nigeria carries the highest burden and diversity of neglected tropical diseases (NTDs) in sub-Saharan Africa and is preparing to scale up its efforts to control/eliminate these diseases. To achieve this it will require a range of internal technical support and expertise for mapping, monitoring and evaluating, operational research and documenting its success. In order to begin to evaluate this potential in Nigeria, this study collated and analysed information for lymphatic filariasis (LF), onchocerciasis, schistosomiasis and soil-transmitted helminths (STH), which are currently being targeted with preventive chemotherapy through mass drug administration (MDA). METHODOLOGY/PRINCIPAL FINDINGS: Information from 299 scientific articles published on the selected NTDs in 179 journals between January 2008 and September 2013 was extracted and systematically compiled into a geo-referenced database for analysis and mapping. The highest number of articles was from the southern geo political zones of the country. The majority of articles focused on one specific disease, and schistosomiasis and STH were found to have the highest and most wide ranging research output. The main type of study was parasitological, and the least was biotechnological. Nigerian authors were mostly affiliated with universities, and there was a wide range of international co-authors from Africa and other regions, especially the USA and UK. The majority of articles were published in journals with no known impact factor. CONCLUSIONS/SIGNIFICANCE: The extensive database and series of maps on the research capacity within Nigeria produced in this study highlights the current potential that exists, and needs to be fully maximized for the control/elimination of NTDs in the country. This study provides an important model approach that can be applied to other low and middle income countries where NTDs are endemic, and NTD programmes require support from the expertise within their own country, as well as internationally, to help raise their profile and importance. PMID- 25121583 TI - Illustrating anticipatory life cycle assessment for emerging photovoltaic technologies. AB - Current research policy and strategy documents recommend applying life cycle assessment (LCA) early in research and development (R&D) to guide emerging technologies toward decreased environmental burden. However, existing LCA practices are ill-suited to support these recommendations. Barriers related to data availability, rapid technology change, and isolation of environmental from technical research inhibit application of LCA to developing technologies. Overcoming these challenges requires methodological advances that help identify environmental opportunities prior to large R&D investments. Such an anticipatory approach to LCA requires synthesis of social, environmental, and technical knowledge beyond the capabilities of current practices. This paper introduces a novel framework for anticipatory LCA that incorporates technology forecasting, risk research, social engagement, and comparative impact assessment, then applies this framework to photovoltaic (PV) technologies. These examples illustrate the potential for anticipatory LCA to prioritize research questions and help guide environmentally responsible innovation of emerging technologies. PMID- 25121585 TI - Direct spectroscopic observation of closed-shell singlet, open-shell singlet, and triplet p-biphenylyloxenium ion. AB - The photophysics and photochemistry of p-biphenylyl hydroxylamine hydrochloride was studied using laser flash photolysis ranging from the femtosecond to the microsecond time scale. The singlet excited state of this photoprecursor is formed within 350 fs and partitions into three different transients that are assigned to the p-biphenyloxy radical, the open-shell singlet p-biphenylyloxenium ion, and the triplet p-biphenylyloxenium ion, having lifetimes of 40 MUs, 45 ps, and 1.6 ns, respectively, in CH3CN. The open-shell singlet p-biphenylyloxenium ion predominantly undergoes internal conversion to produce the closed-shell singlet p-biphenylyloxenium ion, which has a lifetime of 5-20 ns. The longer lived radical is unambiguously assigned by nanosecond time-resolved resonance Raman (ns-TR(3)) spectroscopy, and the assignment of the short-lived singlet and triplet oxenium ion transient absorptions are supported by matching time dependent density functional theory (TD-DFT) predictions of the absorptions of these species, as well as by product studies that implicate the intermediacy of charged electrophilic intermediates. Product studies from photolysis give p biphenylol as the major product and a chloride adduct as the major product when NaCl is added as a trap. Thermolysis studies give p-biphenylol as a major product, as well as water, ammonium, and chloro adducts. These studies provide a rare direct look at a discrete oxenium ion intermediate and the first detection of open-shell singlet and triplet configurations of an oxenium ion, as well as providing an intriguing example of the importance of excited state dynamics in governing the electronic state population of reactive intermediates. PMID- 25121584 TI - Inference of transposable element ancestry. AB - Most common methods for inferring transposable element (TE) evolutionary relationships are based on dividing TEs into subfamilies using shared diagnostic nucleotides. Although originally justified based on the "master gene" model of TE evolution, computational and experimental work indicates that many of the subfamilies generated by these methods contain multiple source elements. This implies that subfamily-based methods give an incomplete picture of TE relationships. Studies on selection, functional exaptation, and predictions of horizontal transfer may all be affected. Here, we develop a Bayesian method for inferring TE ancestry that gives the probability that each sequence was replicative, its frequency of replication, and the probability that each extant TE sequence came from each possible ancestral sequence. Applying our method to 986 members of the newly-discovered LAVA family of TEs, we show that there were far more source elements in the history of LAVA expansion than subfamilies identified using the CoSeg subfamily-classification program. We also identify multiple replicative elements in the AluSc subfamily in humans. Our results strongly indicate that a reassessment of subfamily structures is necessary to obtain accurate estimates of mutation processes, phylogenetic relationships and historical times of activity. PMID- 25121586 TI - A new avenue toward androgen receptor pan-antagonists: C2 sterically hindered substitution of hydroxy-propanamides. AB - The androgen receptor (AR) represents the primary target for prostate cancer (PC) treatment even when the disease progresses toward androgen-independent (AIPC) or castration-resistant (CRPC) forms. Because small chemical changes in the structure of nonsteroidal AR ligands determine the pharmacological responses of AR, we developed a novel stereoselective synthetic strategy that allows sterically hindered C2-substituted bicalutamide analogues to be obtained. Biological and theoretical evaluations demonstrate that C2-substitution with benzyl and phenyl moieties is a new, valuable option toward improving pan antagonist behavior. Among the synthesized compounds, (R)-16m, when compared to casodex, (R)-bicalutamide, and enzalutamide, displayed very promising in vitro activity toward five different prostate cancer cell lines, all representative of CPRC and AIPC typical mutations. Despite being less active than (R)-bicalutamide, (R)-16m also displayed marked in vivo antitumor activity on VCaP xenografts and thus it may serve as starting point for developing novel AR pan-antagonists. PMID- 25121588 TI - Photocatalytic activity of ZnWO4: band structure, morphology and surface modification. AB - Photocatalytic degradation of organic contaminants is an important application area in solar energy utilization. To improve material photocatalytic properties, understanding their photocatalytic mechanism is indispensable. Here, the photocatalytic performance of ZnWO4 nanocrystals was systematicly investigated by the photodegradation of tetraethylated rhodamine (RhB) under simulated sunlight irradiation, including the influence of morphology, AgO/ZnWO4 heterojunction and comparison with CoWO4 nanowires. The results show that the photocatalytic activity of ZnWO4 is higher than that of CoWO4, and the ZnWO4 nanorods exhibit better photocatalytic activity than that of ZnWO4 nanowires. In addition, the mechanism for the difference of the photocatalytic activity was also investigated by comparison of their photoluminescence and photocurrents. AgO nanoparticles were assembled uniformly on the surface of ZnWO4 nanowires to form a heterojunction that exhibited enhanced photocatalytic activity under irradiation at the initial stage. We found that a good photocatalyst should not only have an active structure for electrons directly to transfer from the valence band to the conduction band without the help of phonons but also a special electronic configuration for the high mobility, to ensure more excited electrons and holes in a catalytic reaction. PMID- 25121587 TI - Black and white women in Maryland receive different treatment for cervical cancer. AB - PURPOSE: Despite an overall decrease in incidence, the death rate from cervical cancer in the United States remains higher in black women than their white counterparts. We examined the Maryland Cancer Registry (MCR) to determine treatment factors that may explain differences in outcomes between races in the state of Maryland. METHODS: Incident cervical cancers in the MCR 1992-2008 were examined. Demographics, tumor characteristics and treatments were compared between races and over time. RESULTS: Our analysis included 2034 (1301 white, 733 black) patients. Black women were more likely to have locally advanced or metastatic disease at diagnosis (p<0.01). They were more likely to receive any radiation or chemotherapy combined with radiation and less likely to receive surgery (p<0.01). When adjusted for stage and insurance status black women had 1.50 (95% CI 1.20-1.87) times the odds of receiving radiation and 1.43 (95% CI 1.11-1.82) times the odds of receiving chemotherapy. Black women with cervical cancer had 0.51 times the adjusted odds (95% CI 0.41-0.65) of receiving surgery compared to white women. Racial differences in treatment did not change significantly over time. CONCLUSIONS: Surgical treatment for newly diagnosed cervical cancer in the state of Maryland was significantly less common amongst black women than white during our study period. Equivalent treatments are not being administered to white and black patients with cervical cancer in Maryland. Differences in care may contribute to racial disparities in outcomes for women with cervical cancer. PMID- 25121589 TI - Factors associated with appointment non-adherence among African-Americans with severe, poorly controlled hypertension. AB - BACKGROUND: Missed appointments are associated with an increased risk of hospitalization and mortality. Despite its widespread prevalence, little data exists regarding factors related to appointment non-adherence among hypertensive African-Americans. OBJECTIVE: To investigate factors associated with appointment non-adherence among African-Americans with severe, poorly controlled hypertension. DESIGN AND PARTICIPANTS: A cross-sectional survey of 185 African Americans admitted to an urban medical center in Maryland, with severe, poorly controlled hypertension from 1999-2004. Categorical and continuous variables were compared using chi-square and t-tests. Adjusted multivariable logistic regression was used to assess correlates of appointment non-adherence. MAIN OUTCOME MEASURES: Appointment non-adherence was the primary outcome and was defined as patient-report of missing greater than 3 appointments out of 10 during their lifetime. RESULTS: Twenty percent of participants (n = 37) reported missing more than 30% of their appointments. Patient characteristics independently associated with a higher odds of appointment non-adherence included not finishing high school (Odds ratio [OR] = 3.23 95% confidence interval [CI] (1.33-7.69), hypertension knowledge ([OR] = 1.20 95% CI: 1.01-1.42), lack of insurance ([OR] = 6.02 95% CI: 1.83-19.88), insurance with no medication coverage ([OR] = 5.08 95% CI: 1.05-24.63), cost of discharge medications ([OR] = 1.20 95% CI: 1.01 1.42), belief that anti-hypertensive medications do not work ([OR] = 3.67 95% CI: 1.16-11.7), experience of side effects ([OR] = 3.63 95% CI: 1.24-10.62), medication non-adherence ([OR] = 11.31 95% CI: 3.87-33.10). Substance abuse was not associated with appointment non-adherence ([OR] = 1.05 95% CI: 0.43-2.57). CONCLUSIONS: Appointment non-adherence among African-Americans with poorly controlled hypertension was associated with many markers of inadequate access to healthcare, knowledge, attitudes and beliefs. PMID- 25121590 TI - EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to promote B-cell proliferation. AB - Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the human population. EBV is associated with several types of malignancies originating from lymphoid and epithelial cell types. EBV latent antigen 3C (EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney murine leukemia provirus integration site (PIM-1), which encodes an oncogenic serine/threonine kinase, is linked to several cellular functions involving cell survival, proliferation, differentiation, and apoptosis. Notably, enhanced expression of Pim-1 kinase is associated with numerous hematological and non hematological malignancies. A higher expression level of Pim-1 kinase is associated with EBV infection, suggesting a crucial role for Pim-1 in EBV-induced tumorigenesis. We now demonstrate a molecular mechanism which reveals a direct role for EBNA3C in enhancing Pim-1 expression in EBV-infected primary B-cells. We also showed that EBNA3C is physically associated with Pim-1 through its amino terminal domain, and also forms a molecular complex in B-cells. EBNA3C can stabilize Pim-1 through abrogation of the proteasome/Ubiquitin pathway. Our results demonstrate that EBNA3C enhances Pim-1 mediated phosphorylation of p21 at the Thr145 residue. EBNA3C also facilitated the nuclear localization of Pim-1, and promoted EBV transformed cell proliferation by altering Pim-1 mediated regulation of the activity of the cell-cycle inhibitor p21/WAF1. Our study demonstrated that EBNA3C significantly induces Pim-1 mediated proteosomal degradation of p21. A significant reduction in cell proliferation of EBV transformed LCLs was observed upon stable knockdown of Pim-1. This study describes a critical role for the oncoprotein Pim-1 in EBV-mediated oncogenesis, as well as provides novel insights into oncogenic kinase-targeted therapeutic intervention of EBV-associated cancers. PMID- 25121591 TI - DNA binding and condensation properties of the herpes simplex virus type 1 triplex protein VP19C. AB - Herpesvirus capsids are regular icosahedrons with a diameter of a 125 nm and are made up of 162 capsomeres arranged on a T = 16 lattice. The capsomeres (VP5) interact with the triplex structure, which is a unique structural feature of herpesvirus capsid shells. The triplex is a heterotrimeric complex; one molecule of VP19C and two of VP23 form a three-pronged structure that acts to stabilize the capsid shell through interactions with adjacent capsomeres. VP19C interacts with VP23 and with the major capsid protein VP5 and is required for the nuclear localization of VP23. Mutation of VP19C results in the abrogation of capsid shell synthesis. Analysis of the sequence of VP19C showed the N-terminus of VP19C is very basic and glycine rich. It was hypothesized that this domain could potentially bind to DNA. In this study an electrophoretic mobility shift assay (EMSA) and a DNA condensation assay were performed to demonstrate that VP19C can bind DNA. Purified VP19C was able to bind to both a DNA fragment of HSV-1 origin as well as a bacterial plasmid sequence indicating that this activity is non specific. Ultra-structural imaging of the nucleo-protein complexes revealed that VP19C condensed the DNA and forms toroidal DNA structures. Both the DNA binding and condensing properties of VP19C were mapped to the N-terminal 72 amino acids of the protein. Mutational studies revealed that the positively charged arginine residues in this N-terminal domain are required for this binding. This DNA binding activity, which resides in a non-conserved region of the protein could be required for stabilization of HSV-1 DNA association in the capsid shell. PMID- 25121592 TI - Discovery of a eukaryotic pyrroloquinoline quinone-dependent oxidoreductase belonging to a new auxiliary activity family in the database of carbohydrate active enzymes. AB - Pyrroloquinoline quinone (PQQ) is a redox cofactor utilized by a number of prokaryotic dehydrogenases. Not all prokaryotic organisms are capable of synthesizing PQQ, even though it plays important roles in the growth and development of many organisms, including humans. The existence of PQQ-dependent enzymes in eukaryotes has been suggested based on homology studies or the presence of PQQ-binding motifs, but there has been no evidence that such enzymes utilize PQQ as a redox cofactor. However, during our studies of hemoproteins, we fortuitously discovered a novel PQQ-dependent sugar oxidoreductase in a mushroom, the basidiomycete Coprinopsis cinerea. The enzyme protein has a signal peptide for extracellular secretion and a domain for adsorption on cellulose, in addition to the PQQ-dependent sugar dehydrogenase and cytochrome domains. Although this enzyme shows low amino acid sequence homology with known PQQ-dependent enzymes, it strongly binds PQQ and shows PQQ-dependent activity. BLAST search uncovered the existence of many genes encoding homologous proteins in bacteria, archaea, amoebozoa, and fungi, and phylogenetic analysis suggested that these quinoproteins may be members of a new family that is widely distributed not only in prokaryotes, but also in eukaryotes. PMID- 25121593 TI - Oridonin attenuates Abeta1-42-induced neuroinflammation and inhibits NF-kappaB pathway. AB - Neuroinflammation induced by beta-amyloid (Abeta) plays a critical role in the pathogenesis of Alzheimer's disease (AD), and inhibiting Abeta-induced neuroinflammation serves as a potential strategy for the treatment of AD. Oridonin (Ori), a compound of Rabdosia rubescens, has been shown to exert anti inflammatory effects. In this study, we demonstrated that Ori inhibited glial activation and decreased the release of inflammatory cytokines in the hippocampus of Abeta1-42-induced AD mice. In addition, Ori inhibited the NF-kappaB pathway and Abeta1-42-induced apoptosis. Furthermore, Ori could attenuate memory deficits in Abeta1-42-induced AD mice. In conclusion, our study demonstrated that Ori inhibited the neuroinflammation and attenuated memory deficits induced by Abeta1 42, suggesting that Ori might be a promising candidate for AD treatment. PMID- 25121594 TI - Expression analysis of a stress-related phosphoinositide-specific phospholipase C gene in wheat (Triticum aestivum L.). AB - Plant phosphoinositide-specific phospholipases C (PI-PLCs) function in several essential plant processes associated with either development or environmental stress. In this report, we examined the expression patterns of TaPLC1 under drought and high salinity stress at the transcriptional and post-transcriptional levels. TaPLC1 mRNA was expressed in all wheat organs examined. U73122 and edelfosine, the PLC inhibitor, impaired seedling growth and enhanced seedling sensitivity to drought and high salinity stress. Though TaPLC1 expression in wheat was lowest at the seedling stage, it was strongly induced under conditions of stress. When 6-day-old wheat seedlings were treated with 200 mM NaCl or 20% (w/v) PEG 6000 for 6 or 12 h, respectively, the TaPLC1 transcript level increased by 16-fold compared to the control. Western blotting showed that the TaPLC protein concentration was also maintained at a high level from 24 to 48 h during stress treatment. Together, our results indicate the possible biological functions of TaPLC1 in regulating seedling growth and the response to drought and salinity stress. PMID- 25121596 TI - Vaccine strategies for the control and prevention of Japanese encephalitis in Mainland China, 1951-2011. AB - Japanese encephalitis (JE) is arguably one of the most serious viral encephalitis diseases worldwide. China has a long history of high prevalence of Japanese encephalitis, with thousands of cases reported annually and incidence rates often exceeding 15/100,000. In global terms, the scale of outbreaks and high incidence of these pandemics has almost been unique, placing a heavy burden on the Chinese health authorities. However, the introduction of vaccines, developed in China, combined with an intensive vaccination program initiated during the 1970s, as well as other public health interventions, has dramatically decreased the incidence from 20.92/100,000 in 1971, to 0.12/100,000 in 2011. Moreover, in less readily accessible areas of China, changes to agricultural practices designed to reduce chances of mosquito bites as well as mosquito population densities have also been proven effective in reducing local JE incidence. This unprecedented public health achievement has saved many lives and provided valuable experience that could be directly applicable to the control of vector-borne diseases around the world. Here, we review and discuss strategies for promotion and expansion of vaccination programs to reduce the incidence of JE even further, for the benefit of health authorities throughout Asia and, potentially, worldwide. PMID- 25121595 TI - A neural network approach to fMRI binocular visual rivalry task analysis. AB - The purpose of this study was to investigate whether artificial neural networks (ANN) are able to decode participants' conscious experience perception from brain activity alone, using complex and ecological stimuli. To reach the aim we conducted pattern recognition data analysis on fMRI data acquired during the execution of a binocular visual rivalry paradigm (BR). Twelve healthy participants were submitted to fMRI during the execution of a binocular non rivalry (BNR) and a BR paradigm in which two classes of stimuli (faces and houses) were presented. During the binocular rivalry paradigm, behavioral responses related to the switching between consciously perceived stimuli were also collected. First, we used the BNR paradigm as a functional localizer to identify the brain areas involved the processing of the stimuli. Second, we trained the ANN on the BNR fMRI data restricted to these regions of interest. Third, we applied the trained ANN to the BR data as a 'brain reading' tool to discriminate the pattern of neural activity between the two stimuli. Fourth, we verified the consistency of the ANN outputs with the collected behavioral indicators of which stimulus was consciously perceived by the participants. Our main results showed that the trained ANN was able to generalize across the two different tasks (i.e. BNR and BR) and to identify with high accuracy the cognitive state of the participants (i.e. which stimulus was consciously perceived) during the BR condition. The behavioral response, employed as control parameter, was compared with the network output and a statistically significant percentage of correspondences (p-value <0.05) were obtained for all subjects. In conclusion the present study provides a method based on multivariate pattern analysis to investigate the neural basis of visual consciousness during the BR phenomenon when behavioral indicators lack or are inconsistent, like in disorders of consciousness or sedated patients. PMID- 25121597 TI - CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the abdomen. AB - BACKGROUND: The absence of CDK4 amplification in liposarcomas is associated with favorable prognosis. We aimed to identify the factors associated with tumor recurrence in patients with well-differentiated (WD) and dedifferentiated (DD) liposarcomas. METHODS: From 2000 to 2010, surgical resections for 101 WD and DD liposarcomas were performed. Cases in which complete surgical resections with curative intent were carried out were selected. MDM2 and CDK4 gene amplification were analyzed by quantitative real-time polymerase chain reaction (Q-PCR). RESULTS: There were 31 WD and 17 DD liposarcomas. Locoregional recurrence was observed in 11 WD and 3 DD liposarcomas. WD liposarcomas showed better patient survival compared to DD liposarcomas (P<0.05). Q-PCR analysis of the liposarcomas revealed the presence of CDK4 amplification in 44 cases (91.7%) and MDM2 amplification in 46 cases (95.8%). WD liposarcomas with recurrence after surgical resection had significantly higher levels of CDK4 amplification compared to those without recurrence (P = 0.041). High level of CDK4 amplification (cases with CDK4 amplification higher than the median 7.54) was associated with poor recurrence free survival compared to low CDK4 amplification in both univariate (P = 0.012) and multivariate analyses (P = 0.020). CONCLUSIONS: Level of CDK4 amplification determined by Q-PCR was associated with the recurrence of WD liposarcomas after surgical resection. PMID- 25121598 TI - Logarithmic and power law input-output relations in sensory systems with fold change detection. AB - Two central biophysical laws describe sensory responses to input signals. One is a logarithmic relationship between input and output, and the other is a power law relationship. These laws are sometimes called the Weber-Fechner law and the Stevens power law, respectively. The two laws are found in a wide variety of human sensory systems including hearing, vision, taste, and weight perception; they also occur in the responses of cells to stimuli. However the mechanistic origin of these laws is not fully understood. To address this, we consider a class of biological circuits exhibiting a property called fold-change detection (FCD). In these circuits the response dynamics depend only on the relative change in input signal and not its absolute level, a property which applies to many physiological and cellular sensory systems. We show analytically that by changing a single parameter in the FCD circuits, both logarithmic and power-law relationships emerge; these laws are modified versions of the Weber-Fechner and Stevens laws. The parameter that determines which law is found is the steepness (effective Hill coefficient) of the effect of the internal variable on the output. This finding applies to major circuit architectures found in biological systems, including the incoherent feed-forward loop and nonlinear integral feedback loops. Therefore, if one measures the response to different fold changes in input signal and observes a logarithmic or power law, the present theory can be used to rule out certain FCD mechanisms, and to predict their cooperativity parameter. We demonstrate this approach using data from eukaryotic chemotaxis signaling. PMID- 25121600 TI - Pectinmethylesterases (PME) and pectinmethylesterase inhibitors (PMEI) enriched during phloem fiber development in flax (Linum usitatissimum). AB - Flax phloem fibers achieve their length by intrusive-diffusive growth, which requires them to penetrate the extracellular matrix of adjacent cells. Fiber elongation therefore involves extensive remodelling of cell walls and middle lamellae, including modifying the degree and pattern of methylesterification of galacturonic acid (GalA) residues of pectin. Pectin methylesterases (PME) are important enzymes for fiber elongation as they mediate the demethylesterification of GalA in muro, in either a block-wise fashion or in a random fashion. Our objective was to identify PMEs and PMEIs that mediate phloem fiber elongation in flax. For this purpose, we measured transcript abundance of candidate genes at nine different stages of stem and fiber development and found sets of genes enriched during fiber elongation and maturation as well as during xylem development. We expressed one of the flax PMEIs in E. coli and demonstrated that it was able to inhibit most of the native PME activity in the upper portion of the flax stem. These results identify key genetic components of the intrusive growth process and define targets for fiber engineering and crop improvement. PMID- 25121599 TI - An otx/nodal regulatory signature for posterior neural development in ascidians. AB - In chordates, neural induction is the first step of a complex developmental process through which ectodermal cells acquire a neural identity. In ascidians, FGF-mediated neural induction occurs at the 32-cell stage in two blastomere pairs, precursors respectively of anterior and posterior neural tissue. We combined molecular embryology and cis-regulatory analysis to unveil in the ascidian Ciona intestinalis the remarkably simple proximal genetic network that controls posterior neural fate acquisition downstream of FGF. We report that the combined action of two direct FGF targets, the TGFbeta factor Nodal, acting via Smad- and Fox-binding sites, and the transcription factor Otx suffices to trigger ascidian posterior neural tissue formation. Moreover, we found that this strategy is conserved in the distantly related ascidian Phallusia mammillata, in spite of extreme sequence divergence in the cis-regulatory sequences involved. Our results thus highlight that the modes of gene regulatory network evolution differ with the evolutionary scale considered. Within ascidians, developmental regulatory networks are remarkably robust to genome sequence divergence. Between ascidians and vertebrates, major fate determinants, such as Otx and Nodal, can be co-opted into different networks. Comparative developmental studies in ascidians with divergent genomes will thus uncover shared ascidian strategies, and contribute to a better understanding of the diversity of developmental strategies within chordates. PMID- 25121601 TI - SNP identification by transcriptome sequencing and candidate gene-based association analysis for heat tolerance in the bay scallop Argopecten irradians. AB - The northern bay scallop Argopecten irradians irradians (Lamarck) and the southern bay scallop Argopecten irradians concentricus (Say) were introduced into China in the 1980s and 1990s, and are now major aquaculture molluscs in China. Here, we report the transcriptome sequencing of the two subspecies and the subsequent association analysis on candidate gene on the trait of heat tolerance. In total, RNA from six tissues of 67 and 42 individuals of northern and southern bay scallops, respectively, were used and 55.5 and 34.9 million raw reads were generated, respectively. There were 82,267 unigenes produced in total, of which 32,595 were annotated. Altogether, 32,206 and 23,312 high-quality SNPs were identified for northern and southern bay scallops, respectively. For case-control analysis, two intercrossed populations were heat stress treated, and both heat susceptible and heat-resistant individuals were collected. According to annotation and SNP allele frequency analysis, 476 unigenes were selected, and 399 pairs of primers were designed. Genotyping was conducted using the high resolution melting method, and Fisher's exact test was performed for allele frequency comparison between the heat-susceptible and heat-resistant groups. SNP all-53308-760 T/C showed a significant difference in allele frequency between the heat-susceptible and heat-resistant groups. Notably, considerable difference in allele frequency at this locus was also observed between the sequenced natural populations. These results suggest that SNP all-53308-760 T/C may be related to the heat tolerance of the bay scallop. Moreover, quantitative expression analysis revealed that the expression level of all-53308 was negatively correlated with heat tolerance of the bay scallop. PMID- 25121602 TI - Conserving plants in gene banks and nature: investigating complementarity with Trifolium thompsonii Morton. AB - A standard conservation strategy for plant genetic resources integrates in situ (on-farm or wild) and ex situ (gene or field bank) approaches. Gene bank managers collect ex situ accessions that represent a comprehensive snap shot of the genetic diversity of in situ populations at a given time and place. Although simple in theory, achieving complementary in situ and ex situ holdings is challenging. Using Trifolium thompsonii as a model insect-pollinated herbaceous perennial species, we used AFLP markers to compare genetic diversity and structure of ex situ accessions collected at two time periods (1995, 2004) from four locations, with their corresponding in situ populations sampled in 2009. Our goal was to assess the complementarity of the two approaches. We examined how gene flow, selection and genetic drift contributed to population change. Across locations, we found no difference in diversity between ex situ and in situ samples. One population showed a decline in genetic diversity over the 15 years studied. Population genetic differentiation among the four locations was significant, but weak. Association tests suggested infrequent, long distance gene flow. Selection and drift occurred, but differences due to spatial effects were three times as strong as differences attributed to temporal effects, and suggested recollection efforts could occur at intervals greater than fifteen years. An effective collecting strategy for insect pollinated herbaceous perennial species was to sample >150 plants, equalize maternal contribution, and sample along random transects with sufficient space between plants to minimize intrafamilial sampling. Quantifying genetic change between ex situ and in situ accessions allows genetic resource managers to validate ex situ collecting and maintenance protocols, develop appropriate recollection intervals, and provide an early detection mechanism for identifying problematic conditions that can be addressed to prevent further decline in vulnerable in situ populations. PMID- 25121603 TI - Top-down inputs enhance orientation selectivity in neurons of the primary visual cortex during perceptual learning. AB - Perceptual learning has been used to probe the mechanisms of cortical plasticity in the adult brain. Feedback projections are ubiquitous in the cortex, but little is known about their role in cortical plasticity. Here we explore the hypothesis that learning visual orientation discrimination involves learning-dependent plasticity of top-down feedback inputs from higher cortical areas, serving a different function from plasticity due to changes in recurrent connections within a cortical area. In a Hodgkin-Huxley-based spiking neural network model of visual cortex, we show that modulation of feedback inputs to V1 from higher cortical areas results in shunting inhibition in V1 neurons, which changes the response properties of V1 neurons. The orientation selectivity of V1 neurons is enhanced without changing orientation preference, preserving the topographic organizations in V1. These results provide new insights to the mechanisms of plasticity in the adult brain, reconciling apparently inconsistent experiments and providing a new hypothesis for a functional role of the feedback connections. PMID- 25121605 TI - Temperature and food influence shell growth and mantle gene expression of shell matrix proteins in the pearl oyster Pinctada margaritifera. AB - In this study, we analyzed the combined effect of microalgal concentration and temperature on the shell growth of the bivalve Pinctada margaritifera and the molecular mechanisms underlying this biomineralization process. Shell growth was measured after two months of rearing in experimental conditions, using calcein staining of the calcified structures. Molecular mechanisms were studied though the expression of 11 genes encoding proteins implicated in the biomineralization process, which was assessed in the mantle. We showed that shell growth is influenced by both microalgal concentration and temperature, and that these environmental factors also regulate the expression of most of the genes studied. Gene expression measurement of shell matrix protein thereby appears to be an appropriate indicator for the evaluation of the biomineralization activity in the pearl oyster P. margaritifera under varying environmental conditions. This study provides valuable information on the molecular mechanisms of mollusk shell growth and its environmental control. PMID- 25121604 TI - Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, telethonin): identification of cardiac clock-controlled genes using open access bioinformatics data. AB - Circadian rhythms are important for healthy cardiovascular physiology and are regulated at the molecular level by a circadian clock mechanism. We and others previously demonstrated that 9-13% of the cardiac transcriptome is rhythmic over 24 h daily cycles; the heart is genetically a different organ day versus night. However, which rhythmic mRNAs are regulated by the circadian mechanism is not known. Here, we used open access bioinformatics databases to identify 94 transcripts with expression profiles characteristic of CLOCK and BMAL1 targeted genes, using the CircaDB website and JTK_Cycle. Moreover, 22 were highly expressed in the heart as determined by the BioGPS website. Furthermore, 5 heart enriched genes had human/mouse conserved CLOCK:BMAL1 promoter binding sites (E boxes), as determined by UCSC table browser, circadian mammalian promoter/enhancer database PEDB, and the European Bioinformatics Institute alignment tool (EMBOSS). Lastly, we validated findings by demonstrating that Titin cap (Tcap, telethonin) was targeted by transcriptional activators CLOCK and BMAL1 by showing 1) Tcap mRNA and TCAP protein had a diurnal rhythm in murine heart; 2) cardiac Tcap mRNA was rhythmic in animals kept in constant darkness; 3) Tcap and control Per2 mRNA expression and cyclic amplitude were blunted in Clock(Delta19/Delta19) hearts; 4) BMAL1 bound to the Tcap promoter by ChIP assay; 5) BMAL1 bound to Tcap promoter E-boxes by biotinylated oligonucleotide assay; and 6) CLOCK and BMAL1 induced tcap expression by luciferase reporter assay. Thus this study identifies circadian regulated genes in silico, with validation of Tcap, a critical regulator of cardiac Z-disc sarcomeric structure and function. PMID- 25121606 TI - Impact of hormone-associated resistance to activated protein C on the thrombotic potential of oral contraceptives: a prospective observational study. AB - INTRODUCTION: The increased thrombotic risk of oral contraceptives (OC) has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC). To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use. PATIENTS AND METHODS: Blood samples were collected prospectively from healthy women (n = 21) before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA) technology. Thrombin generation markers and other hemostasis parameters were measured additionally. RESULTS: All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p = 0.0003). Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur. CONCLUSIONS: In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as predictors of OC-associated thrombotic risk. PMID- 25121607 TI - The prevalence and magnitude of impaired cutaneous sensation across the hand in the chronic period post-stroke. AB - Sensation is commonly impaired immediately post-stroke but little is known about the long-term changes in cutaneous sensation that have the capacity to adversely impact independence and motor-function. We investigated cutaneous sensory thresholds across the hand in the chronic post-stroke period. Cutaneous sensation was assessed in 42 community-dwelling stroke patients and compared to 36 healthy subjects. Sensation was tested with calibrated monofilaments at 6 sites on the hand that covered the median, ulnar and radial innervation territories and included both glabrous (hairless) and hairy skin. The motor-function of stroke patients was assessed with the Wolf Motor Function Test and the upper-limb motor Fugl-Meyer Assessment. Impaired cutaneous sensation was defined as monofilament thresholds >3 SD above the mean of healthy subjects and good sensation was <= 3 SD. Cutaneous sensation was impaired for 33% of patients and was 40-84% worse on the more-affected side compared to healthy subjects depending on the site (p<0.05). When the stroke patient data were pooled cutaneous sensation fell within the healthy range, although ~ 1/3 of patients were classified with impaired sensation. Classification by motor-function revealed low levels of impaired sensation. The magnitude of sensory loss was only apparent when the sensory-function of stroke patients was classified as good or impaired. Sensation was most impaired on the dorsum of the hand where age-related changes in monofilament thresholds are minimal in healthy subjects. Although patients with both high and low motor-function had poor cutaneous sensation, overall patients with low motor-function had poorer cutaneous sensation than those with higher motor-function, and relationships were found between motor impairments and sensation at the fingertip and palm. These results emphasize the importance of identifying the presence and magnitude of cutaneous sensory impairments in the chronic period after stroke. PMID- 25121609 TI - Largest genetic survey to date shows major success for giant panda breeding programs. PMID- 25121608 TI - Relationships between the ABC-exporter HetC and peptides that regulate the spatiotemporal pattern of heterocyst distribution in Anabaena. AB - In the model cyanobacterium Anabaena sp. PCC 7120, cells called heterocysts that are specialized in the fixation of atmospheric nitrogen differentiate from vegetative cells of the filament in the absence of combined nitrogen. Heterocysts follow a specific distribution pattern along the filament, and a number of regulators have been identified that influence the heterocyst pattern. PatS and HetN, expressed in the differentiating cells, inhibit the differentiation of neighboring cells. At least PatS appears to be processed and transferred from cell to cell. HetC is similar to ABC exporters and is required for differentiation. We present an epistasis analysis of these regulatory genes and of genes, hetP and asr2819, successively downstream from hetC, and we have studied the localization of HetC and HetP by use of GFP fusions. Inactivation of patS, but not of hetN, allowed differentiation to proceed in a hetC background, whereas inactivation of hetC in patS or patS hetN backgrounds decreased the frequency of contiguous proheterocysts. A HetC-GFP protein is localized to the heterocysts and especially near their cell poles, and a putative HetC peptidase domain was required for heterocyst differentiation but not for HetC-GFP localization. hetP is also required for heterocyst differentiation. A HetP-GFP protein localized mostly near the heterocyst poles. ORF asr2819, which we denote patC, encodes an 84-residue peptide and is induced upon nitrogen step-down. Inactivation of patC led to a late spreading of the heterocyst pattern. Whereas HetC and HetP appear to have linked functions that allow heterocyst differentiation to progress, PatC may have a role in selecting sites of differentiation, suggesting that these closely positioned genes may be functionally related. PMID- 25121610 TI - The HIV-1 envelope transmembrane domain binds TLR2 through a distinct dimerization motif and inhibits TLR2-mediated responses. AB - HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR) responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD) of the HIV-1 envelope (ENV) directly interacts with TLR2 TMD within the membrane milieu. This interaction attenuates TNFalpha, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models. This was associated with decreased levels of ERK phosphorylation. Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu. The administration of the ENV TMD in vivo to lipotechoic acid (LTA)/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation. Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection. Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation. PMID- 25121611 TI - Exogenous lactate supply affects lactate kinetics of rainbow trout, not swimming performance. AB - Intense swimming causes circulatory lactate accumulation in rainbow trout because lactate disposal (Rd) is not stimulated as strongly as lactate appearance (Ra). This mismatch suggests that maximal Rd is limited by tissue capacity to metabolize lactate. This study uses exogenous lactate to investigate what constrains maximal Rd and minimal Ra. Our goals were to determine how exogenous lactate affects: 1) Ra and Rd of lactate under baseline conditions or during graded swimming, and 2) exercise performance (critical swimming speed, Ucrit) and energetics (cost of transport, COT). Results show that exogenous lactate allows swimming trout to boost maximal Rd lactate by 40% and reach impressive rates of 56 MUmol.kg(-1).min(-1). This shows that the metabolic capacity of tissues for lactate disposal is not responsible for setting the highest Rd normally observed after intense swimming. Baseline endogenous Ra (resting in normoxic water) is not significantly reduced by exogenous lactate supply. Therefore, trout have an obligatory need to produce lactate, either as a fuel for oxidative tissues and/or from organs relying on glycolysis. Exogenous lactate does not affect Ucrit or COT, probably because it acts as a substitute for glucose and lipids rather than extra fuel. We conclude that the observed 40% increase in Rd lactate is made possible by accelerating lactate entry into oxidative tissues via monocarboxylate transporters (MCTs). This observation together with the weak expression of MCTs and the phenomenon of white muscle lactate retention show that lactate metabolism of rainbow trout is significantly constrained by transmembrane transport. PMID- 25121612 TI - Cold water immersion enhances recovery of submaximal muscle function after resistance exercise. AB - We investigated the effect of cold water immersion (CWI) on the recovery of muscle function and physiological responses after high-intensity resistance exercise. Using a randomized, cross-over design, 10 physically active men performed high-intensity resistance exercise followed by one of two recovery interventions: 1) 10 min of CWI at 10 degrees C or 2) 10 min of active recovery (low-intensity cycling). After the recovery interventions, maximal muscle function was assessed after 2 and 4 h by measuring jump height and isometric squat strength. Submaximal muscle function was assessed after 6 h by measuring the average load lifted during 6 sets of 10 squats at 80% of 1 repetition maximum. Intramuscular temperature (1 cm) was also recorded, and venous blood samples were analyzed for markers of metabolism, vasoconstriction, and muscle damage. CWI did not enhance recovery of maximal muscle function. However, during the final three sets of the submaximal muscle function test, participants lifted a greater load (P < 0.05, Cohen's effect size: 1.3, 38%) after CWI compared with active recovery. During CWI, muscle temperature decreased ~7 degrees C below postexercise values and remained below preexercise values for another 35 min. Venous blood O2 saturation decreased below preexercise values for 1.5 h after CWI. Serum endothelin-1 concentration did not change after CWI, whereas it decreased after active recovery. Plasma myoglobin concentration was lower, whereas plasma IL-6 concentration was higher after CWI compared with active recovery. These results suggest that CWI after resistance exercise allows athletes to complete more work during subsequent training sessions, which could enhance long-term training adaptations. PMID- 25121613 TI - Pushing the limits of blood pressure control under severe heat stress. Focus on "Active and passive heat stress similarly compromise tolerance to a simulated hemorrhagic challenge". PMID- 25121614 TI - Autophagy is essential to support skeletal muscle plasticity in response to endurance exercise. AB - Physical exercise is a stress that can substantially modulate cellular signaling mechanisms to promote morphological and metabolic adaptations. Skeletal muscle protein and organelle turnover is dependent on two major cellular pathways: Forkhead box class O proteins (FOXO) transcription factors that regulate two main proteolytic systems, the ubiquitin-proteasome, and the autophagy-lysosome systems, including mitochondrial autophagy, and the MTORC1 signaling associated with protein translation and autophagy inhibition. In recent years, it has been well documented that both acute and chronic endurance exercise can affect the autophagy pathway. Importantly, substantial efforts have been made to better understand discrepancies in the literature on its modulation during exercise. A single bout of endurance exercise increases autophagic flux when the duration is long enough, and this response is dependent on nutritional status, since autophagic flux markers and mRNA coding for actors involved in mitophagy are more abundant in the fasted state. In contrast, strength and resistance exercises preferentially raise ubiquitin-proteasome system activity and involve several protein synthesis factors, such as the recently characterized DAGK for mechanistic target of rapamycin activation. In this review, we discuss recent progress on the impact of acute and chronic exercise on cell component turnover systems, with particular focus on autophagy, which until now has been relatively overlooked in skeletal muscle. We especially highlight the most recent studies on the factors that can impact its modulation, including the mode of exercise and the nutritional status, and also discuss the current limitations in the literature to encourage further works on this topic. PMID- 25121616 TI - The association of serum vitamin D concentration with serious complications after noncardiac surgery. AB - BACKGROUND: Vitamin D deficiency is a global health problem. Epidemiological studies demonstrate that vitamin D is both cardioprotective and neuroprotective. Vitamin D also plays a substantial role in innate and acquired immunity. Our goal was to evaluate the association of serum vitamin D concentration on serious postoperative complications and death in noncardiac surgical patients. METHODS: We retrospectively analyzed the data of 3509 patients who had noncardiac surgery at the Cleveland Clinic Main Campus and had a serum vitamin D measurement. The relationship between serum vitamin D concentration and all-cause in-hospital mortality, in-hospital cardiovascular morbidity, and serious in-hospital infections was assessed as a common effect odds ratio (OR) by using a multivariate generalized estimating equation model with adjustment for demographic, medical history variables, and type and duration of surgery. RESULTS: Higher vitamin D concentrations were associated with decreased odds of in-hospital mortality/morbidity (P = 0.003). There was a linear reduction of the corresponding common effect odds ratio (OR 0.93, 95% confidence interval, 0.88 0.97) for severe in-hospital outcomes for each 5 ng/mL increase in vitamin D concentration over the range from 4 to 44 ng/mL. In addition, we found that the odds versus patients with vitamin D <13 ng/mL (i.e., 1st quintile) were significantly lower in patients with vitamin D 13-20, 20-27, 27-36, and > 36 ng/mL (i.e., 2nd-5th quintiles); the corresponding estimated ORs were 0.65 (99% confidence interval, 0.43-0.98), 0.53 (0.35-0.80), 0.44 (0.28-0.70), and 0.49 (0.31-0.78), respectively. However, there was no statistically significant difference among individual quintiles >13 ng/mL. CONCLUSIONS: Vitamin D concentrations were associated with a composite of in-hospital death, serious infections, and serious cardiovascular events in patients recovering from noncardiac surgery. While causality cannot be determined from our retrospective analysis, the association suggests that a large randomized trial of preoperative vitamin D supplementation and postoperative outcomes is warranted. PMID- 25121617 TI - Cooling strategies targeting trauma. PMID- 25121615 TI - Cadherin cytoplasmic domains inhibit the cell surface localization of endogenous E-cadherin, blocking desmosome and tight junction formation and inducing cell dissociation. AB - The downregulation of E-cadherin function has fundamental consequences with respect to cancer progression, and occurs as part of the epithelial-mesenchymal transition (EMT). In this study, we show that the expression of the Discosoma sp. red fluorescent protein (DsRed)-tagged cadherin cytoplasmic domain in cells inhibited the cell surface localization of endogenous E-cadherin, leading to morphological changes, the inhibition of junctional assembly and cell dissociation. These changes were associated with increased cell migration, but were not accompanied by the down-regulation of epithelial markers and up regulation of mesenchymal markers. Thus, these changes cannot be classified as EMT. The cadherin cytoplasmic domain interacted with beta-catenin or plakoglobin, reducing the levels of beta-catenin or plakoglobin associated with E-cadherin, and raising the possibility that beta-catenin and plakoglobin sequestration by these constructs induced E-cadherin intracellular localization. Accordingly, a cytoplasmic domain construct bearing mutations that weakened the interactions with beta-catenin or plakoglobin did not impair junction formation and adhesion, indicating that the interaction with beta-catenin or plakoglobin was essential to the potential of the constructs. E-cadherin-alpha-catenin chimeras that did not require beta-catenin or plakoglobin for their cell surface transport restored cell-cell adhesion and junction formation. PMID- 25121618 TI - Long-term benefits versus side-effects from bone-targeted therapies for cancer patients: minimizing risk while maximizing benefits. AB - PURPOSE OF REVIEW: Bone-targeted therapies such as bisphosphonates and denosumab are established in the treatment of cancer patients to prevent or delay skeletal related events and improve quality of life. Along with these benefits of bone targeted therapies, there are also known risks and adverse effects. RECENT FINDINGS: Although historically bone-targeted therapy use has been limited to palliation in patients with bone metastases, recent evidence suggests that these agents may also have anti-cancer effects. This will likely lead to the greater use of these agents in patients with earlier-stage disease. Increased use will lead to more adverse effects. In particular, the risk of rare but severe toxicities will become important. SUMMARY: This article explores strategies to maximize the clinical benefit of such therapy while minimizing associated risks. PMID- 25121621 TI - Edentulous persons, United States-1971. AB - There were an estimated 22.6 million edentulous persons in the United States according to the Health Interview Survey conducted in 1971. The Ju1y 1957-June 1958 survey estimate of the number of persons who were edentulous (had lost all their natural teeth) was 21.9 million. Since in most instances it takes many years of dental neglect for an individual to lose all his teeth, persons with no teeth are heavily concentrated in the older age groups. For example, in 1971,86.3 percent (19.5 million) of the edentulous population were in the age group 45 years of age and older, while in 1957-58 the comparable figure was 85.2 percent. Virtually every American will be affected during his or her lifetime by dental decay or periodontal disease. Reports previously published in the Vital and Health Statistics series contain national estimates of the prevalence, severity, and effects of dental disease among U.S. adults. Based on dental examinations conducted during 1960-62, it was estimated that approximately 20 million adults had lost all their natural teeth. Of the remaining adults with at least one natural tooth (approximately 90 million), about haIf had 18 or more decayed, missing, or filled teeth. In addition, about three out of four of those with natural teeth had periodontal disease, and about one out of four had an advanced form of periodontal disease with pocket formations. The result of neglected dental caries and advanced periodontal disease is the loss of teeth. Persons using artificial dentures are considerably less efficient at chewing than persons with healthy natural teeth. For the aged, artificial dentures mean a decrease in masticator function at a time when an efficient dental function is increasingly desirable due to changes in nutritional requirements. While the ultimate dental health goaI is the eradication of dental disease, an important immediate goal is the reduction of tooth Ioss. Tooth loss can usualIy be obviated by diagnosing and treating dental disease in its early stages and by utilizing the preventive measures now available. PMID- 25121620 TI - Evaluation of an mHealth intervention aiming to improve health-related behavior and sleep and reduce fatigue among airline pilots. AB - OBJECTIVES: The aim of this study was to evaluate the effects of an mHealth intervention (intervention using mobile technology) consisting of tailored advice regarding exposure to daylight, sleep, physical activity, and nutrition, and aiming to improve health-related behavior, thereby reducing sleep problems and fatigue and improving health perception of airline pilots. METHODS: A randomized controlled trial was conducted among 502 airline pilots. The intervention group was given access to both the MORE Energy mobile application (app) with tailored advice and a website with background information. The control group was directed to a website with standard information about fatigue. Health-related behavior, fatigue, sleep, and health perception outcomes were measured through online questionnaires at baseline and at three and six months after baseline. The effectiveness of the intervention was determined using linear and Poisson mixed model analyses. RESULTS: After six months, compared to the control group, the intervention group showed a significant improvement on fatigue (beta= -3.76, P<0.001), sleep quality (beta= -0.59, P=0.007), strenuous physical activity (beta=0.17, P=0.028), and snacking behavior (beta= -0.81, P<0.001). No significant effects were found for other outcome measures. CONCLUSIONS: The MORE Energy mHealth intervention reduced self-reported fatigue compared to a minimal intervention. Some aspects of health-related behavior (physical activity and snacking behavior) and sleep (sleep quality) improved as well, but most did not. The results show offering tailored advice through an mHealth intervention is an effective means to support employees who have to cope with irregular flight schedules and circadian disruption. This kind of intervention might therefore also be beneficial for other working populations with irregular working hours. PMID- 25121619 TI - Optimization of photoactive protein Z for fast and efficient site-specific conjugation of native IgG. AB - Antibody conjugates have been used in a variety of applications from immunoassays to drug conjugates. However, it is becoming increasingly clear that in order to maximize an antibody's antigen binding ability and to produce homogeneous antibody-conjugates, the conjugated molecule should be attached onto IgG site specifically. We previously developed a facile method for the site-specific modification of full length, native IgGs by engineering a recombinant Protein Z that forms a covalent link to the Fc domain of IgG upon exposure to long wavelength UV light. To further improve the efficiency of Protein Z production and IgG conjugation, we constructed a panel of 13 different Protein Z variants with the UV-active amino acid benzoylphenylalanine (BPA) in different locations. By using this panel of Protein Z to cross-link a range of IgGs from different hosts, including human, mouse, and rat, we discovered two previously unknown Protein Z variants, L17BPA and K35BPA, that are capable of cross-linking many commonly used IgG isotypes with efficiencies ranging from 60% to 95% after only 1 h of UV exposure. When compared to existing site-specific methods, which often require cloning or enzymatic reactions, the Protein Z-based method described here, utilizing the L17BPA, K35BPA, and the previously described Q32BPA variants, represents a vastly more accessible and efficient approach that is compatible with nearly all native IgGs, thus making site-specific conjugation more accessible to the general research community. PMID- 25121622 TI - Activation of the D1 receptors inhibits the long-term potentiation in vivo induced by acute morphine administration through a D1-GluN2A interaction in the nucleus accumbens. AB - Dopamine D1-like receptors can modulate glutamate-mediated excitatory synaptic neurotransmission, but the underlying molecular mechanism remains elusive. Here, we report that acute in-vivo morphine administration induces the long-term potentiation (Mor-LTP) of field excitatory postsynaptic potentials at the prefrontal cortex-to-nucleus accumbens shell synapses, and this process requires the activation of GluN2A-containing N-methyl-D-aspartate receptors. This Mor-LTP is completely inhibited by the D1-like receptor agonist SKF81297, but not by the D2-like receptor agonist quinpirole. SKF81297-inhibited Mor-LTP is restored by pretreatment with the TAT-conjugated interfering peptide TAT-D1-t3, which is a synthetic blocker of the direct D1-GluN2A receptor interaction. These results indicate that the activation of D1 receptors modulates Mor-LTP by the direct D1 GluN2A interaction at the prefrontal cortex-to-nucleus accumbens shell synapses and might play a role in addiction-related plastic alterations. PMID- 25121623 TI - Electrophysiological response to omitted stimulus in sentence processing. AB - The current study provides evidence that the absence of a syntactically expected item leads to a sustained cognitive processing demand. Event-related potentials were measured at the omission of a syntactically expected object argument in a speech sequence. English monolingual adults listened to paired sentences. The first sentence in the pair established a context. The second sentence provided a response to the first sentence that was either grammatically correct by containing an overt object argument in the form of a pronoun, or was syntactically unacceptable by omitting the expected object pronoun. Event-related potentials measured at the omission of the object argument showed a prolonged positivity for 100-600 ms with a broad scalp distribution, and for 600-1000 ms with a focus in the anterior region. This observed omitted stimulus potential may contain characteristics of the P300 component, associated with the detection of the deviation of an expected stimulus, and the classical P600 related to syntactic reanalysis. Further, the late anterior P600 may indicate an increased memory demand in sentence comprehension. Thus, this linguistic omitted stimulus potential is a cognitive indicator of language processing that can be used to investigate the organization of linguistic knowledge. PMID- 25121625 TI - Primary pure signet-ring cell carcinoma of the anus: a case report with immunohistochemical study. PMID- 25121624 TI - Acupuncture-induced changes in functional connectivity of the primary somatosensory cortex varied with pathological stages of Bell's palsy. AB - Bell's palsy is the most common cause of acute facial nerve paralysis. In China, Bell's palsy is frequently treated with acupuncture. However, its efficacy and underlying mechanism are still controversial. In this study, we used functional MRI to investigate the effect of acupuncture on the functional connectivity of the brain in Bell's palsy patients and healthy individuals. The patients were further grouped according to disease duration and facial motor performance. The results of resting-state functional MRI connectivity show that acupuncture induces significant connectivity changes in the primary somatosensory region of both early and late recovery groups, but no significant changes in either the healthy control group or the recovered group. In the recovery group, the changes also varied with regions and disease duration. Therefore, we propose that the effect of acupuncture stimulation may depend on the functional connectivity status of patients with Bell's palsy. PMID- 25121626 TI - Signet-ring cell carcinoma of the nonampullary duodenum and proximal jejunum: a case report with an immunohistochemical study. PMID- 25121627 TI - Gastric gastrointestinal stromal tumor lost in the peritoneum after endoscopic resection. PMID- 25121628 TI - Doxycycline-induced pill esophagitis. PMID- 25121629 TI - Large polypoid lymphoid follicles in the stomach causing anemia. PMID- 25121631 TI - Endoscopic ultrasound-guided thrombin injection in a large splenic artery aneurysm: first report in a patient with tropical chronic pancreatitis. PMID- 25121632 TI - The "death" of lethal injection as we know it? The role of chemical execution in the American criminal justice system. AB - Several independent elements have recently combined to thrust United States capital punishment into a chaos. Corrections officials and policy makers have attempted to "humanize" capital punishment by evolving into a chemical execution process, and soften the outward appearance. Foreign policies have interrupted chemical protocols by banning key ingredients. These disruptions are spawning new theories of legal challenges in capital punishment. This is a critical time for stakeholders and all members of a civilized society to pause and reflect on the role of capital punishment. PMID- 25121630 TI - Extensive small-bowel Crohn's disease detected by the newly introduced 360 degrees panoramic viewing capsule endoscopy system. PMID- 25121633 TI - An introduction to "keeping the 'health' in health communication": a column devoted to interdisciplinary vocabulary. AB - Health communication research and practice often involve interdisciplinary collaborations. These endeavors include vocabularies associated with the different disciplines and backgrounds of the collaborators. This feature will be devoted to providing glossaries to introduce these vocabularies. PMID- 25121634 TI - One-step synthesis of graphene-Au nanoparticle hybrid materials from metal salt loaded micelles. AB - In this study, we present a facile one-step method to synthesize graphene-Au nanoparticle (NP) hybrid materials by using HAuCl4-loaded poly(styrene)-block poly(2-vinylpyridine) (PS-P2VP) micelles as solid carbon sources. N-doped graphene with controllable thickness can be grown from PS-P2VP micelles covered by a Ni capping layer by an annealing process; simultaneously, the HAuCl4 in the micelles were reduced into Au NPs under a reductive atmosphere to form Au NPs on graphene. The decoration of Au NPs leads to an obviously enhanced electrical conductivity and a slightly increased work function of graphene due to the electron transfer effect. The graphene-Au NP hybrid materials also exhibit a localized surface plasmon resonance feature of Au NPs. This work provides a novel and accessible route for the one-step synthesis of graphene-Au NP hybrid materials with high quality, which might be useful for future applications in optoelectronic devices. PMID- 25121635 TI - Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice. AB - The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment. PMID- 25121636 TI - Congenital hemophagocytic lymphohistiocytosis presenting as thrombocytopenia in a newborn. AB - Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by dysregulation and hyperactivation of the immune system, and can be familial or acquired. HLH presenting in infancy can be rapidly fatal if not promptly recognized and treated. Congenital HLH can be caused by various genetic mutations or part of immunodeficiency syndromes. We present an infant with Griscelli syndrome and familial HLH with atypical genetic mutations, presenting as thrombocytopenia on the first day of life, cured with chemotherapy and unrelated cord blood transplant. PMID- 25121637 TI - Adjuvant Gemcitabine and Gemcitabine-based Chemoradiotherapy Versus Gemcitabine Alone After Pancreatic Cancer Resection: The Indiana University Experience. AB - OBJECTIVES: Adjuvant therapy after surgical resection is the current standard for pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains unclear. This study was conducted to compare the efficacy outcomes with adjuvant gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy (CT) alone after pancreaticoduodenectomy. METHODS: Among 165 patients who underwent surgical resection for pancreatic cancer at Indiana University Medical Center between 2004 and 2008, we retrospectively identified 53 consecutive patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and had adequate follow-up medical records. The median follow-up was 19.1 months. Median disease-free (DFS) and overall survival (OS) were determined using Kaplan Meier method, and a Cox-regression model was used to compare survival outcomes after adjusting for age, status of resection margins, and lymph node involvement. RESULTS: The OS for the CT-CRT group was significantly higher compared with the CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group (hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly superior OS and DFS were observed among patients younger than 65 years, T3/T4 tumor stage, negative resection margins, and positive lymph node involvement. CONCLUSION: Gemcitabine plus gemcitabine-based CRT compared with gemcitabine alone leads to superior DFS and OS for patients with resected pancreatic cancer. PMID- 25121638 TI - Competitive immunochromatographic assay for the detection of thiodiglycol sulfoxide, a degradation product of sulfur mustard. AB - An immunochromatographic assay (ICA) based on the competitive antigen-coated format using colloidal gold as the label was developed for the detection of thiodiglycol sulfoxide (TDGO), an important metabolite and degradation compound of sulphur mustard (SM). The ICA test strip consisted of a membrane with a detection zone, a sample pad and an absorbent pad. The membrane was separately coated with hapten-OVA conjugate (test line) and anti-rabbit mouse IgG (control line). The visual detection limit for TDGO by ICA detection was found to be 10 MUg mL(-1). For validation, the ICA results obtained for spiked water samples were in good agreement with those obtained by indirect competitive inhibition enzyme-linked immunosorbent assay (ELISA) for TDGO. The assay time for detection was less than 10 min. The developed ICA has the potential to be a useful on-site screening tool for the retrospective detection of SM in environmental samples. PMID- 25121639 TI - Significance and costs of complex biopsychosocial health care needs in elderly people: results of a population-based study. AB - OBJECTIVE: To improve health care for the elderly, a consideration of biopsychosocial health care needs may be of particular importance-especially because of the prevalence of multiple conditions, mental disorders, and social challenges facing elderly people. The aim of the study was to investigate significance and costs of biopsychosocial health care needs in elderly people. METHODS: Data were derived from the 8-year follow-up of the ESTHER study-a German epidemiological study in the elderly population. A total of 3124 participants aged 57 to 84 years were visited at home by trained medical doctors. Biopsychosocial health care needs were assessed using the INTERMED for the Elderly (IM-E) interview. Health-related quality of life (HRQOL) was measured by the 12-Item Short-Form Health Survey, and psychosomatic burden was measured by the Patient Health Questionnaire. RESULTS: The IM-E correlated with decreased mental (mental component score: r = -0.38, p < .0001) and physical HRQOL (physical component score: r = -0.45, p < .0001), increased depression severity (r = 0.53, p < .0001), and costs (R = 0.41, p < .0001). The proportion of the participants who had an IM-E score of at least 21 was 8.2%; according to previous studies, they were classified as complex patients (having complex biopsychosocial health care needs). Complex patients showed a highly reduced HRQOL compared with participants without complex health care needs (mental component score: 37.0 [10.8] versus 48.7 [8.8]; physical component score: 33.0 [9.1] versus 41.6 [9.5]). Mean health care costs per 3 months of complex patients were strongly increased (1651.1 &OV0556; [3192.2] versus 764.5 &OV0556; [1868.4]). CONCLUSIONS: Complex biopsychosocial health care needs are strongly associated with adverse health outcomes in elderly people. It should be evaluated if interdisciplinary treatment plans would improve the health outcomes for complex patients. PMID- 25121640 TI - Quantitative Trait Loci from Two Genotypes of Oat (Avena sativa) Conditioning Resistance to Puccinia coronata. AB - Developing oat cultivars with partial resistance to crown rust would be beneficial and cost-effective for disease management. Two recombinant inbred-line populations were generated by crossing the susceptible cultivar Provena with two partially resistant sources, CDC Boyer and breeding line 94197A1-9-2-2-2-5. A third mapping population was generated by crossing the partially resistant sources to validate the quantitative trait locus (QTL) results. The three populations were evaluated for crown rust severity in the field at Louisiana State University (LSU) in 2009 and 2010 and at the Cereal Disease Laboratory (CDL) in St. Paul, MN, in 2009, 2010, and 2011. An iSelect platform assay containing 5,744 oat single nucleotide polymorphisms was used to genotype the populations. From the 2009 CDL test, linkage analyses revealed two QTLs for partial resistance in the Provena/CDC Boyer population on chromosome 19A. One of the 19A QTLs was also detected in the 2009 LSU test. Another QTL was detected on chromosome 12D in the CDL 2009 test. In the Provena/94197A1-9-2-2-2-5 population, only one QTL was detected, on chromosome 13A, in the CDL 2011 test. The 13A QTL from the Provena/94197A1-9-2-2-2-5 population was validated in the CDC Boyer/94197A1-9-2-2-2-5 population in the CDL 2010 and 2011 tests. Comparative analysis of the significant marker sequences with the rice genome database revealed 15 candidate genes for disease resistance on chromosomes 4 and 6 of rice. These genes could be potential targets for cloning from the two resistant parents. PMID- 25121641 TI - Regional and field-specific factors affect the composition of fusarium head blight pathogens in subtropical no-till wheat agroecosystem of Brazil. AB - A multiyear survey of >200 wheat fields in Parana (PR) and Rio Grande do Sul (RS) states was conducted to assess the extent and distribution of Fusarium graminearum species complex (FGSC) diversity in the southern Brazilian wheat agroecosystem. Five species and three trichothecene genotypes were found among 671 FGSC isolates from Fusarium head blight (FHB)-infected wheat heads: F. graminearum (83%) of the 15-acetyldeoxynivalenol (15-ADON) genotype, F. meridionale (12.8%) and F. asiaticum (0.4%) of the nivalenol (NIV) genotype, and F. cortaderiae (2.5%) and F. austroamericanum (0.9%) with either the NIV or the 3 ADON genotype. Regional differences in FGSC composition were observed, with F. meridionale and the NIV type being significantly (P<0.001) more prevalent in PR (>28%) than in RS (<=9%). Within RS, F. graminearum was overrepresented in fields below 600 m in elevation and in fields with higher levels of FHB incidence (P<0.05). Species composition was not significantly influenced by previous crop or the stage of grain development at sampling. Habitat-specific differences in FGSC composition were evaluated in three fields by characterizing a total of 189 isolates collected from corn stubble, air above the wheat canopy, and symptomatic wheat kernels. Significant differences in FGSC composition were observed among these habitats (P<0.001). Most strikingly, F. meridionale and F. cortaderiae of the NIV genotype accounted for the vast majority (>96%) of isolates from corn stubble, whereas F. graminearum with the 15-ADON genotype was dominant (>84%) among isolates from diseased wheat kernels. Potential differences in pathogenic fitness on wheat were also suggested by a greenhouse competitiveness assay in which F. graminearum was recovered at much higher frequency (>90%) than F. meridionale from four wheat varieties inoculated with an equal mixture of F. graminearum and F. meridionale isolates. Taken together, the data presented here suggest that FGSC composition and, consequently, the trichothecene contamination in wheat grown in southern Brazil is influenced by host adaptation and pathogenic fitness. Evidence that F. meridionale and F. cortaderiae with the NIV genotype are regionally significant contributors to FHB may have significant implications for food safety and the economics of cereal production. PMID- 25121642 TI - Evidence for Systemic Infection by Puccinia horiana, Causal Agent of Chrysanthemum White Rust, in Chrysanthemum. AB - Puccinia horiana, causal agent of the disease commonly known as chrysanthemum white rust (CWR), is a quarantine-significant fungal pathogen of chrysanthemum in the United States and indigenous to Asia. The pathogen was believed to have been eradicated in the United States but recently reappeared on several occasions in northeastern United States. The objective of the study presented here was to determine whether P. horiana could systemically infect chrysanthemum plants, thus providing a means of survival through winters. Scanning and transmission electron microscopy revealed the development of P. horiana on the surface and within leaves, stems, or crowns of inoculated chrysanthemum plants artificially exposed to northeastern U.S. winter temperatures. P. horiana penetrated leaves directly through the cuticle and then colonized the mesophyll tissue both inter- and intracellularly. An electron-dense material formed at the interface between fungal and host mesophyll cells, suggesting that the pathogen adhered to the plant cells. P. horiana appeared to penetrate mesophyll cell walls by enzymatic digestion, as indicated by the absence of deformation lines in host cell walls at penetration sites. The fungus was common in vascular tissue within the infected crown, often nearly replacing the entire contents of tracheid cell walls. P. horiana frequently passed from one tracheid cell to an adjacent tracheid cell by penetration either through pit pairs or nonpitted areas of the cell walls. Individual, presumed, fungal cells in mature tracheid cells of the crown and stems arising from infected crowns suggested that the pathogen might have been moving at least partially by means of the transpiration stream. The demonstration that chrysanthemum plants can be systemically infected by P. horiana suggests that additional disease control measures are required to effectively control CWR. PMID- 25121644 TI - Ab initio chemical synthesis of designer metal phosphate frameworks at ambient conditions. AB - Stepwise hierarchical and rational synthesis of porous zinc phosphate frameworks by predictable and directed assembly of easily isolable tetrameric zinc phosphate [Zn(dipp)(solv)]4 (dippH2 = diisopropylphenyldihydrogen phosphate; solv = CH3OH or dimethyl sulfoxide) with D4R (double-4-ring) topology has been achieved. The preformed and highly robust D4R secondary building unit can be coordinatively interconnected through a varied choice of bipyridine-based ditopic spacers L1-L7 to isolate eight functional zinc phosphate frameworks, [Zn4(dipp)4(L1)1.5(DMSO)].4H2O (2), [Zn4(dipp)4(L2)1.5(CH3OH)] (3), [Zn4(dipp)4(L1)2] (4), [Zn4(dipp)4(L3)2] (5), [Zn4(dipp)4(L4)2] (6), [Zn4(dipp)4(L5)2] (7), [Zn4(dipp)4(L6)2] (8), and [Zn4(dipp)4(L7)2] (9), in good yield. The preparative procedures are simple and do not require high pressure or temperature. Surface area measurements of these framework solids show that the guest accessibility of the frameworks can be tuned by suitable modification of bipyridine spacers. PMID- 25121643 TI - Sodium dodecyl sulfate monomers induce XAO peptide polyproline II to alpha-helix transition. AB - XAO peptide (Ac-X2A7O2-NH2; X: diaminobutyric acid side chain, -CH2CH2NH3(+); O: ornithine side chain, -CH2CH2CH2NH3(+)) in aqueous solution shows a predominantly polyproline II (PPII) conformation without any detectable alpha-helix-like conformations. Here we demonstrate by using circular dichroism (CD), ultraviolet resonance Raman (UVRR) and nuclear magnetic resonance (NMR) spectroscopy that sodium dodecyl sulfate (SDS) monomers bind to XAO and induce formation of alpha helix-like conformations. The stoichiometry and the association constants of SDS and XAO were determined from the XAO-SDS diffusion coefficients measured by pulsed field gradient NMR. We developed a model for the formation of XAO-SDS aggregate alpha-helix-like conformations. Using UVRR spectroscopy, we calculated the Ramachandran psi angle distributions of aggregated XAO peptides. We resolved alpha-, pi- and 3(10)-helical conformations and a turn conformation. XAO nucleates SDS aggregation at SDS concentrations below the SDS critical micelle concentration. The XAO4-SDS16 aggregates have four SDS molecules bound to each XAO to neutralize the four side chain cationic charges. We propose that the SDS alkyl chains partition into a hydrophobic core to minimize the hydrophobic area exposed to water. Neutralization of the flanking XAO charges enables alpha-helix formation. Four XAO-SDS4 aggregates form a complex with an SDS alkyl chain dominated hydrophobic core and a more hydrophilic shell where one face of the alpha-helix peptide contacts the water environment. PMID- 25121646 TI - Determining asymptotically large population sizes in insect swarms. AB - Social animals commonly form aggregates that exhibit emergent collective behaviour, with group dynamics that are distinct from the behaviour of individuals. Simple models can qualitatively reproduce such behaviour, but only with large numbers of individuals. But how rapidly do the collective properties of animal aggregations in nature emerge with group size? Here, we study swarms of Chironomus riparius midges and measure how their statistical properties change as a function of the number of participating individuals. Once the swarms contain order 10 individuals, we find that all statistics saturate and the swarms enter an asymptotic regime. The influence of environmental cues on the swarm morphology decays on a similar scale. Our results provide a strong constraint on how rapidly swarm models must produce collective states. But our findings support the feasibility of using swarms as a design template for multi-agent systems, because self-organized states are possible even with few agents. PMID- 25121645 TI - Physical activity, sedentary behavior and risk of hypertensive disorders of pregnancy in Hispanic women. AB - OBJECTIVE: Prior studies of the association between physical activity and hypertensive disorders of pregnancy have been conflicting; the majority focused on leisure-time activity only, did not use physical activity questionnaires validated for pregnancy, and were conducted in primarily non-Hispanic white populations. METHODS: We prospectively evaluated this association among 1240 Hispanic women in Proyecto Buena Salud. The Pregnancy Physical Activity Questionnaire, validated for use in pregnancy, was used to assess pre- and early pregnancy sports/exercise, household/caregiving, occupational and transportation activity. Diagnoses of hypertensive disorders of pregnancy were based on medical record abstraction and confirmed by the study obstetrician. RESULTS: A total of 49 women (4.0%) were diagnosed with a hypertensive disorder of pregnancy, including 32 women (2.6%) with pre-eclampsia. In age-adjusted analyses, high levels of early pregnancy household/caregiving activity were associated with reduced risk of total hypertensive disorders (OR = 0.4, 95% CI 0.1-0.9) and pre eclampsia (OR = 0.3, 95% CI 0.1-0.9) relative to low levels; however, these findings were no longer statistically significant in multivariable models. Pre pregnancy activity and pattern of activity from pre- to early-pregnancy were not significantly associated with risk. Finally, sedentary behavior was not significantly associated with hypertensive disorders. CONCLUSION: Findings from this prospective study of Hispanic women were consistent with those of prior prospective cohorts indicating that physical activity prior to and during early pregnancy does not significantly reduce risk of hypertensive disorders of pregnancy. PMID- 25121647 TI - Programming chemistry in DNA-addressable bioreactors. AB - We present a formal calculus, termed the chemtainer calculus, able to capture the complexity of compartmentalized reaction systems such as populations of possibly nested vesicular compartments. Compartments contain molecular cargo as well as surface markers in the form of DNA single strands. These markers serve as compartment addresses and allow for their targeted transport and fusion, thereby enabling reactions of previously separated chemicals. The overall system organization allows for the set-up of programmable chemistry in microfluidic or other automated environments. We introduce a simple sequential programming language whose instructions are motivated by state-of-the-art microfluidic technology. Our approach integrates electronic control, chemical computing and material production in a unified formal framework that is able to mimic the integrated computational and constructive capabilities of the subcellular matrix. We provide a non-deterministic semantics of our programming language that enables us to analytically derive the computational and constructive power of our machinery. This semantics is used to derive the sets of all constructable chemicals and supermolecular structures that emerge from different underlying instruction sets. Because our proofs are constructive, they can be used to automatically infer control programs for the construction of target structures from a limited set of resource molecules. Finally, we present an example of our framework from the area of oligosaccharide synthesis. PMID- 25121648 TI - Interfacial and biological properties of the gradient coating on polyamide substrate for bone substitute. AB - Fabrication of bioactive and mechanical matched bone substitutes is crucial for clinical application in bone defects repair. In this study, nano hydroxyapatite/polyamide (nHA/PA) composite was coated on injection-moulded PA by a chemical corrosion and phase-inversion technique. The shear strength, gradient composition and pore structure of the bioactive coating were characterized. Osteoblast-like MG63 cells were cultured on pure PA and composite-coated PA samples. The cells' adhesion, spread and proliferation were determined using MTT assay and microscopy. The results confirm that the samples with the nHA/PA composite coating have better cytocompatibility and have no negative effects on cells. To investigate the in vivo biocompatibility, both pure PA and composite coated PA cylinders were implanted in the trochlea of rabbit femurs and studied histologically, and the bonding ability with bone were determined using push-out tests. The results show that composite-coated implants exhibit better biocompatibility and the shear strength of the composite-coated implants with host bone at 12 weeks can reach 3.49+/-0.42 MPa, which is significantly higher than that of pure PA implants. These results indicate that composite-coated PA implants have excellent biocompatibility and bonding abilities with host bone and they have the potential to be applied in repair of bone defects. PMID- 25121652 TI - Polarization-sensitive OFDI using polarization-multiplexed wavelength-swept laser. AB - We demonstrate a novel polarization-sensitive optical frequency domain imaging system employing passive polarization multiplexing. Simple modification of a fiber delay line in the wavelength-swept light source enables illumination with two perpendicular polarizations that are required for determination of the Stokes vector components of the light reflected from each depth of the tissue. This simple all-passive approach provides a robust and low-cost solution for PS imaging replacing relatively complex conventional schemes such as polarization modulation or frequency-encoded polarization multiplexing. PMID- 25121651 TI - Real-time optoacoustic tomography of indocyanine green perfusion and oxygenation parameters in human finger vasculature. AB - We interrogated whether optoacoustic tomography could be employed to study blood functional parameters and biodistribution of injected fluorescent agents in humans. Using a multichannel scanner at a frame rate of 10 images per second, we obtained cross-sectional images of the human finger in real time, before and after the administration of indocyanine green. We demonstrated that multispectral optoacoustic tomography can sense fast flow kinetics and resolve spatiotemporal characteristics of a common fluorochrome in human vasculature at clinically relevant concentrations. We further register ICG images with oxygen saturation maps and anatomical views of the proximal interphalangeal joint of a healthy volunteer. PMID- 25121653 TI - Broadband angular filtering with a volume Bragg grating and a surface grating pair. AB - We propose and perform broadband angular filtering with the combination of a volume Bragg grating and a surface grating pair. The condition for broadband operation is discussed. Near-field modulation, contrast ratio, and power spectral density are used to evaluate the filtering performances in the spatial and frequency domain. Experimental results show that the bandwidth of the output beam through the grating combination is remarkably increased, and the medium and high frequencies are effectively eliminated. PMID- 25121650 TI - Masticatory biomechanics in the rabbit: a multi-body dynamics analysis. AB - Multi-body dynamics is a powerful engineering tool which is becoming increasingly popular for the simulation and analysis of skull biomechanics. This paper presents the first application of multi-body dynamics to analyse the biomechanics of the rabbit skull. A model has been constructed through the combination of manual dissection and three-dimensional imaging techniques (magnetic resonance imaging and micro-computed tomography). Individual muscles are represented with multiple layers, thus more accurately modelling muscle fibres with complex lines of action. Model validity was sought through comparing experimentally measured maximum incisor bite forces with those predicted by the model. Simulations of molar biting highlighted the ability of the masticatory system to alter recruitment of two muscle groups, in order to generate shearing or crushing movements. Molar shearing is capable of processing a food bolus in all three orthogonal directions, whereas molar crushing and incisor biting are predominately directed vertically. Simulations also show that the masticatory system is adapted to process foods through several cycles with low muscle activations, presumably in order to prevent rapidly fatiguing fast fibres during repeated chewing cycles. Our study demonstrates the usefulness of a validated multi-body dynamics model for investigating feeding biomechanics in the rabbit, and shows the potential for complementing and eventually reducing in vivo experiments. PMID- 25121649 TI - An explicit immunogenetic model of gastrointestinal nematode infection in sheep. AB - Gastrointestinal nematodes are a global cause of disease and death in humans, wildlife and livestock. Livestock infection has historically been controlled with anthelmintic drugs, but the development of resistance means that alternative controls are needed. The most promising alternatives are vaccination, nutritional supplementation and selective breeding, all of which act by enhancing the immune response. Currently, control planning is hampered by reliance on the faecal egg count (FEC), which suffers from low accuracy and a nonlinear and indirect relationship with infection intensity and host immune responses. We address this gap by using extensive parasitological, immunological and genetic data on the sheep-Teladorsagia circumcincta interaction to create an immunologically explicit model of infection dynamics in a sheep flock that links host genetic variation with variation in the two key immune responses to predict the observed parasitological measures. Using our model, we show that the immune responses are highly heritable and by comparing selective breeding based on low FECs versus high plasma IgA responses, we show that the immune markers are a much improved measure of host resistance. In summary, we have created a model of host-parasite infections that explicitly captures the development of the adaptive immune response and show that by integrating genetic, immunological and parasitological understanding we can identify new immune-based markers for diagnosis and control. PMID- 25121654 TI - Direct comparison of optical lattice clocks with an intercontinental baseline of 9000 km. AB - We have demonstrated a direct frequency comparison between two 87Sr lattice clocks operated in intercontinentally separated laboratories in real time. Two way satellite time and frequency transfer technique, based on the carrier-phase, was employed for a direct comparison, with a baseline of 9000 km between Japan and Germany. A frequency comparison was achieved for 83,640 s, resulting in a fractional difference of (1.1+/-1.6)*10-15, where the statistical part is the largest contributor to the uncertainty. This measurement directly confirms the agreement of the two optical frequency standards on an intercontinental scale. PMID- 25121655 TI - Polarization-resolved near-backscattering of airborne aggregates composed of different primary particles. AB - We measured the polarization-resolved angular elastic scattering intensity distribution of aggregates composed of primary particles with different shapes and packing densities in the near-backward directions (155 degrees -180 degrees ). Specifically, we compare aggregates composed of spherical polystyrene latex spheres, cylinder-like Bacillus subtilis particles, and Arizona road dust, as well as tryptophan particles. We observe clearly differentiable polarization aspect ratios and find that the negative polarization dip is more pronounced in more densely packed aggregates or particles. This work indicates that the polarization aspect ratio in the near-backward direction may be used as a fingerprint to discriminate between aggregates with the same size and overall shape by differences in their constituent particles. PMID- 25121656 TI - Phase-predictable tuning of single-frequency optical synthesizers. AB - We investigate the tuning behavior of a novel type of single-frequency optical synthesizers by phase comparison of the output signals of two identical devices. We achieve phase-stable and cycle-slip free frequency tuning over 28.1 GHz with a maximum zero-to-peak phase deviation of 62 mrad. In contrast to previous implementations of single-frequency optical synthesizers, no comb line order switching is needed when tuned over more than one comb line spacing range of the employed frequency comb. PMID- 25121657 TI - Control of chromaticity by phosphor in glasses with low temperature sintered silicate glasses for LED applications. AB - Phosphor-in-glass (PiG) color converters for LED applications were fabricated with a mixture of phosphors, Y3Al5O12:Ce3+ (yellow) and CaAlSiN3:Eu2+ (red). The low sintering temperature (550 degrees C) of SiO2-Na2O-RO (R=Ba, Zn) glass powder enabled the inclusion of CaAlSiN3:Eu2+ (red) phosphor which cannot be embedded with conventional glass powders for PiGs. By simply varying the mixing ratio of glass to phosphors as well as the ratio of yellow to red phosphors, the facile control of the CIE chromaticity coordinates and correlated color temperature of the LED following the Planckian locus has been achieved. Phosphors were well distributed within the glass matrix without noticeable reactions, preserving the enhanced thermal quenching property of the PiG compared to those with silicone resins, for LEDs. PMID- 25121658 TI - Plasmon mode characteristics of metallic nanowire in uniaxial anisotropic dielectric. AB - The plasmon mode characteristics of metallic nanowire embedded in a uniaxial anisotropic dielectric are investigated theoretically. The hybrid plasmon modes found in this structure are significantly different from the traditional plasmon modes of metallic nanowire in a homogeneous isotropic dielectric. In contrast to the transverse-magnetic-like wave for a traditional fundamental mode, the hybrid fundamental mode of metallic nanowire involves a nonzero longitudinal magnetic field component. The degenerate behaviors of adjacent order plasmon modes are demonstrated in the case of a strongly anisotropic dielectric. Moreover, the dependence of the degenerate characteristics on the radius of a metallic nanowire and the excited wavelength are clearly shown by dispersion relation. The results of the study provide a useful approach to modulate surface plasmon polaritons with anisotropic medium. PMID- 25121659 TI - Possibility of direct estimation of terahertz pulse electric field. AB - In this Letter, we introduce a new method of estimation of the terahertz (THz) field amplitude. This method uses second-harmonic generation (SHG) in the presence of THz and DC fields in gaseous media. We take into account contributions from both nonionized molecules and free plasma electrons to the nonlinear process of SHG. We analyze the applicability of this method of detection to obtaining correct information on the waveform and amplitude of broadband THz pulses. PMID- 25121660 TI - Polarization-dependent study of THz air-biased coherent detection. AB - We present an investigation of the polarization dependence of THz air-biased coherent detection (ABCD) on the polarization directions of fundamental waves. The intensity, ellipticity, and polarization angle of the THz-field-induced second-harmonic are affected by the air plasma birefringence and can be predicted by cross-phase modulation theory. Due to the plasma birefringence, the polarization state of THz waves cannot be determined by the polarization state of the second harmonic with the traditional polarization measurement method. It would be inaccurate to measure arbitrary THz-wave polarization in a single scan with THz ABCD when the birefringence effect is significant. PMID- 25121661 TI - Giant Goos-Hanchen shift in scattering: the role of interfering localized plasmon modes. AB - The longitudinal and transverse beam shifts, namely, the Goos-Hanchen (GH) and the Spin-Hall (SH) shifts are usually observed at planar interfaces. It has recently been shown that the transverse SH shift may also arise due to scattering of plane waves. Here, we show that analogous in-plane (longitudinal) shifts also exist in the scattering of plane waves from micro/nano systems. We study both the GH and the SH shifts in plasmonic metal nanoparticles/nanostructures and dielectric micro-particles employing a unified framework that utilizes the transverse components of the Poynting vector of the scattered wave. The results demonstrate that the interference of neighboring resonance modes in plasmonic nanostructures (e.g., electric dipolar and quadrupolar modes in metal spheres) leads to great enhancement of the GH shift in scattering from such systems. We also unravel interesting correlations between these shifts with the polarimetry parameters, diattenuation and retardance. PMID- 25121662 TI - Rigorous speckle simulation using surface integral equations and higher order boundary element method. AB - The scattering of electromagnetic waves from rough surfaces has been actively studied for more than a century now because of its involvement in vast application areas. In the past two decades, great advances have been made by incorporating multiple scattering effects into analytical approaches. However, no model can yet be applied to surfaces with arbitrary roughness. It is also very difficult to study the cross-polarization, shadowing, or multiple scattering effects. In order to study more fundamentally the interaction of polarized light with more general rough surfaces of general media, we have developed a rigorous numerical simulator to calculate the resulting speckle fields. The full Maxwell equations were solved using surface integral equations combined with a boundary element method. The rough surface was discretized by higher order quadrilateral edge elements. The effective tangential electric and magnetic fields in each element in terms of 10 edges were first solved. The scattered electric and magnetic fields everywhere in space were then calculated correspondingly. One of the great advantages of such a simulator is that both the near and far fields can be calculated directly. Preliminary results of different kinds of metallic structures are presented, by which the advantages of the method are demonstrated. PMID- 25121663 TI - Surface plasmons in nanowires with toroidal magnetic structure. AB - We consider the problem of the influence of a toroidal magnetization on a cylindrical surface plasmon polariton (SPP) propagating along a nanowire of a circular cross section. It follows from the dispersion equations that the SPP wavenumber linearly depends on the toroidal moment and the effect of magneto optical nonreciprocity appears. The numerical solution of the dispersion equations demonstrates that the corresponding splitting of the SPP dispersion curves for two opposite directions of the toroidal moment is increased by an order of magnitude with respect to the planar case. The largest values of this splitting are observed for systems with relatively low optical losses, as is demonstrated by calculations for SPPs in a gold cylinder surrounded by rare-earth bismuth iron garnet. PMID- 25121664 TI - Sub-10-fs pulses tunable from 480 to 980 nm from a NOPA pumped by an Yb:KGW source. AB - We describe two noncollinear optical parametric amplifier (NOPA) systems pumped by either the second (515 nm) or the third (343 nm) harmonic from an Yb:KGW source. Pulse durations as short as 6.8 fs are readily obtained by compression with chirped mirrors. The availability of both the second and third harmonics for NOPA pumping allows for gap-free tuning from 520 to 980 nm. The use of an intermediate NOPA to generate seed light at 780 nm extends the tuning range of the third harmonic pumped NOPA toward 450 nm. PMID- 25121665 TI - Flexible operability and amplification of gray pulses. AB - We have investigated experimentally the flexible production and amplification of gray pulses for the first time to our knowledge. Switchable wavelengths, tunable pulse-widths, and adjustable contrasts have all been obtained in a fiber laser. Amplification of gray pulses was also experimentally investigated in detail. The contrast of the pulses could also be increased in an amplifier. The robust stability that results from the interactions between adjacent harmonic mode locking counterparts of gray pulses was found to last for up to ten hours. To the best of our knowledge, the gray pulses trains we have generated are the most stable achieved to date in an all-fiber laser system. This finding can be used as a guide for the establishment of robust gray pulses as laser sources. PMID- 25121666 TI - Ultralong photonic nanojet formed by a two-layer dielectric microsphere. AB - A photonic nanojet is a highly focused optical beam with a subwavelength waist on the shadow side of the sphere. Successful far-field applications require long nanojets that extend afar. Using the exact Mie theory, we show that ultralong nanojets can be generated using a simple two-layer microsphere structure, using conventional optical materials that are readily available. In particular, we show that for a glass-based two-layer microsphere, the nanojet has an extension of 22 wavelengths. We also show that long nanojets can be formed using semiconductors at infrared frequencies in free space. PMID- 25121667 TI - Time-resolved coherent Raman spectroscopy by high-speed pump-probe delay scanning. AB - Using a spinning window pump-probe delay scanner, we demonstrate a means of acquiring time-resolved vibrational spectra at rates up to 700 Hz. The time dependent phase shift accumulated by the probe pulse in the presence of a coherently vibrating sample gives rise to a Raman-induced frequency shifting readily detectable in a balanced detector. This rapid delay scanning system represents a 23-fold increase in averaging speed and is >10* faster than state-of the-art voice coil delay lines. These advancements make pump-probe spectroscopy a more practical means of imaging complex media. PMID- 25121668 TI - Nanoscale TiO2-coated LPGs as radiation-tolerant humidity sensors for high-energy physics applications. AB - This Letter deals with a feasibility analysis for the development of radiation tolerant fiber-optic humidity sensors based on long-period grating (LPG) technology to be applied in high-energy physics (HEP) experiments currently running at the European Organization for Nuclear Research (CERN). In particular, here we propose a high-sensitivity LPG sensor coated with a finely tuned titanium dioxide (TiO2) thin layer (~100 nm thick) through the solgel deposition method. Relative humidity (RH) monitoring in the range 0%-75% and at four different temperatures (in the range -10 degrees C-25 degrees C) was carried out to assess sensor performance in real operative conditions required in typical experiments running at CERN. Experimental results demonstrate the very high RH sensitivities of the proposed device (up to 1.4 nm/% RH in correspondence to very low humidity levels), which turned out to be from one to three orders of magnitude higher than those exhibited by fiber Bragg grating sensors coated with micrometer-thin polyimide overlays. The radiation tolerance capability of the TiO2-coated LPG sensor is also investigated by comparing the sensing performance before and after its exposure to a 1 Mrad dose of gamma-ionizing radiation. Overall, the results collected demonstrate the strong potential of the proposed technology with regard to its future exploitation in HEP applications as a robust and valid alternative to the commercial (polymer-based) hygrometers currently used. PMID- 25121669 TI - Generation of 9 MeV gamma-rays by all-laser-driven Compton scattering with second harmonic laser light. AB - Gamma-ray photons with energy >9 MeV were produced when second-harmonic generated laser light (3 eV) inverse-Compton-scattered from a counterpropagating relativistic (~450 MeV) laser-wakefield-accelerated electron beam. Two laser pulses from the same laser system were used: one to accelerate electrons and one to scatter. Since the two pulses play very different roles in the gamma-ray generation process, and thus have different requirements, a novel laser system was developed. It separately and independently optimized the optical properties of the two pulses. This approach also mitigated the deleterious effects on beam focusing that generally accompany nonlinear optics at high peak-power levels. PMID- 25121670 TI - Dark state lasers. AB - We propose a new type of laser resonator based on imaginary energy-level splitting (imaginary coupling or quality factor Q-splitting) in a pair of coupled microcavities. A particularly advantageous arrangement involves two microring cavities with different free-spectral ranges in a configuration wherein they are coupled by far-field interference in a shared radiation channel. A novel Vernier like effect for laser resonators is designed in which only one longitudinal resonant mode has a lower loss than the small-signal gain and can achieve lasing while all other modes are suppressed. This configuration enables ultrawidely tunable single-frequency lasers based on either homogeneously or inhomogeneously broadened gain media. The concept is an alternative to the common external cavity configurations for achieving tunable single-mode operation in a laser. The proposed laser concept builds on a high-Q "dark state," which is established by radiative interference coupling and bears a direct analogy to parity-time symmetric Hamiltonians in optical systems. Variants of this concept should be extendable to parametric-gain-based oscillators, enabling widely tunable single frequency light sources. PMID- 25121671 TI - Enhanced XUV pulse generation at 89 nm via nonlinear interaction of UV femtosecond filaments. AB - We demonstrated efficient generation of ultrafast extreme ultraviolet (XUV) pulses at 89 nm from an intense 267 nm UV femtosecond filamentation in argon gas. The XUV pulse generation efficiency was significantly enhanced through UV filament termination from the argon gas into the background vacuum that prevented backconversion of the generated third-harmonic XUV to the fundamental-wave UV pulses. This was further combined with noncollinear UV filament interaction that produced volume-plasma to pre-extract XUV pulses from the filament core, resulting in further XUV enhancement. The generated 89 nm XUV pulses reached what is so far, to our knowledge, the highest pulse energy of 190 nJ. PMID- 25121672 TI - Monolithically integrated selectable repetition-rate laser diode source of picosecond optical pulses. AB - We describe the characterization of a monolithically integrated photonic device for short pulse generation featuring a mode-locked laser diode, a Mach-Zehnder modulator (MZM), and a semiconductor optical amplifier (SOA). The integrated device is designed for fabrication by a generic foundry scheme with a view to ease of design, testing, and manufacture. Trains of 6.8 ps pulses are generated at repetition rates that are electronically switchable from 14 GHz to 109 MHz. The SOA boosts the peak power by 7.4 dB, and the pulses are compressible to 2.4 ps by dispersion compensation using single-mode telecommunications fiber. PMID- 25121673 TI - Reweighted L1 regularization for restraining artifacts in FMT reconstruction images with limited measurements. AB - In fluorescence molecular tomography (FMT), many artifacts exist in the reconstructed images because of the inherently ill-posed nature of the FMT inverse problem, especially with limited measurements. A new method based on iterative reweighted L1 (IRL1) regularization is proposed for reducing artifacts with limited measurements. Phantom experiments demonstrate that the reconstructed images have fewer artifacts even with very limited measurements. This indicates that FMT based on IRL1 can obtain high-quality images and thus has the potential to observe dynamic changes in fluorescence-targeted molecules. PMID- 25121674 TI - Investigating diamond Raman lasers at the 100 W level using quasi-continuous-wave pumping. AB - Quasi-cw pumping is used to investigate the high-power characteristics of cw beam conversion in diamond Raman lasers (DRLs). We show that thermal gradients establish in DRLs at approximately 50 MUs for a 100 MUm pump beam diameter, and thus that the steady state for cw operation can be reached within the 100-300 MUs pulse duration of conventional quasi-cw pump laser technology. Using this approach, a steady-state on-time output power of 108 W was obtained from an external-cavity DRL during 250 MUs pulses with 34% conversion efficiency. No thermal lens in the diamond was evident, showing excellent prospects for further power scaling. PMID- 25121676 TI - Multiwavelength phase unwrapping and aberration correction using depth filtered digital holography. AB - In this Letter, we present a new approach to processing data from a standard spectral domain optical coherence tomography (OCT) system using depth filtered digital holography (DFDH). Intensity-based OCT processing has an axial resolution of the order of a few micrometers. When the phase information is used to obtain optical path length differences, subwavelength accuracy can be achieved, but this limits the resolvable step heights to half of the wavelength of the system. Thus there is a metrology gap between phase- and intensity-based methods. Our concept addresses this metrology gap by combining DFHD with multiwavelength phase unwrapping. Additionally, the measurements are corrected for aberrations. Here, we present proof of concept measurements of a structured semiconductor sample. PMID- 25121675 TI - L(p) regularization for early gate fluorescence molecular tomography. AB - Time domain fluorescence molecular tomography (TD-FMT) provides a unique dataset for enhanced quantification and spatial resolution. The time-gate dataset can be divided into two temporal groups around the maximum counts gate, which are early gates and late gates. It is well established that early gates allow for improved spatial resolution and late gates are essential for fluorophore unmixing and concentration quantification. However, the inverse problem of FMT is ill-posed and typically underdetermined, which makes image reconstruction highly susceptible to data noise. More specifically, photon counts are inherently very low at early gates due to high absorption and scattering of tissue, resulting in a low signal-to-noise ratio and unstable reconstructions. In this work, an L(p) regularization-based reconstruction algorithm was developed and tested with our wide-field mesh-based Monte Carlo simulation strategy. We compared the early time gate reconstructions obtained with the different p (p?{1/16,1/8,1/4,1/3,1/2,1,2}) from a synthetic murine model simulating the fluorophore uptake in the kidneys and preclinical data. The results from a 3D mouse atlas and a mouse experiment show that our L(1/4) regularization methods give the best performance for early time gates reconstructions. PMID- 25121677 TI - Excellent optical thermometry based on single-color fluorescence in spherical NaEuF4 phosphor. AB - Temperature-dependent luminescence of spherical NaEuF4 phosphors with different particle sizes was studied. The thermally coupled 5D0 and 5D1 level of Eu3+ was observed. The linear dependence of emission intensities of 5D0 level of NaEuF4 phosphor on temperature confirmed the excellent temperature sensing performance. Sensitivity up to 0.43% is achieved via decreasing the particle size, which is higher than that of reported thermometry based on upconversion of lanthanide ions. Moreover, the original luminescent intensity of 90% was recovered after 10 temperature-changed cycles, indicating good sensing stability. Therefore, spherical NaEuF4 phosphor might be a promising candidate for optical temperature sensors. PMID- 25121678 TI - Ultrahigh-capacity access network architecture for mobile data backhaul using integrated W-band wireless and free-space optical links with OAM multiplexing. AB - In this Letter, we propose and experimentally demonstrate a novel access network architecture using hybrid integrated W-band wireless and free-space optical (FSO) links with orbital angular momentum (OAM) multiplexing. The transmission of a 20 GBd quadrature phase-shift keying signal modulated over 10 OAM modes has been demonstrated over a 0.6 m FSO link and a 0.4 m W-band wireless link at 100 GHz. The experimental results show that the architecture can support future ultrahigh capacity, converged optical-wireless access networks that require extra bandwidth and system flexibility in mobile data networks. PMID- 25121679 TI - Surface and thickness profile measurement of a transparent film by three wavelength vertical scanning interferometry. AB - We have developed a novel areal film thickness and topography measurement method using three-wavelength interferometry. The method simultaneously estimates the profiles of the front and back surfaces and the thickness distribution of a transparent film by model-based separation of two overlapped signals in an interferogram. The validity of the proposed method is demonstrated using computer simulations and actual experiments. PMID- 25121680 TI - Edge extraction using a time-varying vortex beam in incoherent digital holography. AB - Edge extraction using a time-varying vortex beam (TV-VB) is demonstrated in optical scanning holography (OSH) operating in an incoherent mode. OSH is a two pupil heterodyne scanning optical system. We propose that one of the pupil functions used is a delta function and the other pupil function is a spiral phase plate (SPP). The interference of these pupils creates a TV-VB to scan over an object to record the edge-only information of an object holographically. We also find that a reconstructed edge with better contrast is achieved by translating the SPP away from the pupil plane. Experimental results are compared with computer simulations and found to be in good agreement. PMID- 25121681 TI - Optomechanically induced transparency in the mechanical-mode splitting regime. AB - We employ a decoupled Heisenberg-Langevin equation for the observation and physical interpretation of mechanical-mode splitting (MMS) of the movable mirror in a generic optomechanical system. Then we identify some observable and significant features of MMS in a two-mode cavity. That is, the second control field coupled to another optical mode is input to the system to modify the mechanical mode, leading to the suppression of transmission, the appearance of the doublet in the spectrum of the anti-Stokes field, and the emergence of optomechanically induced transparency in corresponding new mechanical modes. Furthermore, we open two transparent windows in virtue of MMS and find the second splitting of the mechanical mode in this two-mode optomechanical system. PMID- 25121683 TI - Two types of sinc Schell-model beams and their propagation characteristics. AB - Two types of partially coherent beams with sinc Schell-model-correlated function are introduced. The evolution behaviors of scalar beams generated by these two types of sources in free space are investigated with the help of the weighted superposition method and numerical examples. It is illustrated that the far field produced by these two novel sources carry tunable flat and dark hollow profiles, respectively. Our results suggest two new kinds of modal structure of the correlation source and of the optical field that such sources produce. PMID- 25121682 TI - Si/ZnO nanocomb arrays decorated with Ag nanoparticles for highly efficient surface-enhanced Raman scattering. AB - High-density ZnO nanocombs were first grown on a nanoporous silicon pillar array, and pre-prepared 3D Si/ZnO/Ag nanocomb arrays were employed as substrates for surface-enhanced Raman scattering (SERS). The finite-difference time-domain simulation result shows that two kinds of inter-Ag-NP nanogaps in the geometry create a large number of SERS "hot spots," which contributes to the detection limits for rhodamine-6G as low as 10-12 M and the Raman enhancement factor as large as 109. The linear dependence between the Raman peak intensities and the concentrations of thiram provides a new calibration method for rapid and quantitative detection of trace organic molecules. PMID- 25121684 TI - Generalized description of spectral incoherent solitons. AB - Spectral incoherent solitons (SIS) refer to an incoherent solitonic structure that only can be identified in the frequency domain and which is sustained by noninstantaneous Raman-like nonlinearities. We provide a generalized formulation of SIS by considering the generalized nonlinear Schrodinger equation. We show that nonlinear dispersive effects (e.g., self-steepening) dramatically affect the structure of SIS, in particular by significantly decelerating their spectral velocity in frequency space. The wave turbulence description of the problem reveals an underlying self-organization process: the soliton trajectory in frequency space is selected in such a way that it allows the system to self organize into a stationary SIS state. PMID- 25121686 TI - Modulational instability in dispersion oscillating fiber ring cavities. AB - We show that the use of a dispersion oscillating fiber in passive cavities significantly extends the modulational instability to novel high-frequency bands, which also destabilizes the branches of the steady response that are stable with homogeneous dispersion. By means of Floquet theory, we obtain the exact explicit expression for the sideband gain, and a simple analytical estimate for the frequencies of the maximum gain. Numerical simulations show that stable stationary trains of pulses can be excited in the cavity. PMID- 25121685 TI - Abnormal high-Q modes of coupled stadium-shaped microcavities. AB - It is well known that the strongly deformed microcavity with fully chaotic ray dynamics cannot support high-Q modes due to its fast chaotic diffusion to the critical line of refractive emission. Here, we investigate how the Q factor is modified when two chaotic cavities are coupled, and show that some modes, whose Q factor is about 10 times higher than that of the corresponding single cavity, can exist. These abnormal high-Q modes are the result of an optimal combination of coupling and cavity geometry. As an example, in the coupled stadium-shaped microcavities, the mode pattern extends over both cavities such that it follows a whispering-gallery-type mode at both ends, whereas a big coupling spot forms at the closest contact of the two microcavities. The pattern of such a "rounded bow tie" mode allows the mode to have a high-Q factor. This mode pattern minimizes the leakage of light at both ends of the microcavities as the pattern at both ends is similar to the whispering gallery mode. PMID- 25121687 TI - Germanium p-i-n avalanche photodetector fabricated by point defect healing process. AB - In this Letter, we report Ge p-i-n avalanche photodetectors (APD) with low dark current (sub 1 MUA below V(R)=5 V), low operating voltage (avalanche breakdown voltage=8-13 V), and high multiplication gain (440-680) by exploiting a point defect healing method (between 600 degrees C and 650 degrees C) and optimizing the doping concentration of the intrinsic region (p-type ~1017 cm-3). In addition, Raman spectroscopy and electrochemical capacitance voltage analyses were performed to investigate the junction interfaces in more detail. This successful demonstration of Ge p-i-n APD with low dark current, low operating voltage, and high gain is promising for low-power and high-sensitivity Ge PD applications. PMID- 25121688 TI - Omnidirectional light absorption of disordered nano-hole structure inspired from Papilio ulysses. AB - Butterflies routinely produce nanostructured surfaces with useful properties. Here, we report a disordered nano-hole structure with ridges inspired by Papilio ulysses that produce omnidirectional light absorption compared with the common ordered structure. The result shows that the omnidirectional light absorption is affected by polarization, the incident angle, and the wavelength. Using the finite-difference time-domain (FDTD) method, the stable omnidirectional light absorption is achieved in the structure inspired from the Papilio ulysses over a wide incident angle range and with various wavelengths. This explains some of the mysteries of the structure of the Papilio ulysses butterfly. These conclusions can guide the design of omnidirectional absorption materials. PMID- 25121689 TI - Distortion-free wide-angle 3D imaging and visualization using off-axially distributed image sensing. AB - We propose a new off-axially distributed image sensing (ODIS) using a wide-angle lens for reconstructing distortion-free wide-angle slice images computationally. In the proposed system, the wide-angle image sensor captures a wide-angle 3D scene, and thus the collected information of the 3D objects is severely distorted. To correct this distortion, we introduce a new correction process involving a wide-angle lens to the computational reconstruction in ODIS. This enables us to reconstruct distortion-free, wide-angle slice images for visualization of 3D objects. Experimental results are carried out to verify the proposed method. To the best of our knowledge, this is the first time the use of a wide-angle lens in a multiple-perspective 3D imaging system is described. PMID- 25121690 TI - Stable localized modes in asymmetric waveguides with gain and loss. AB - It is shown that asymmetric waveguides with gain and loss can support a stable propagation of optical beams. This means that the propagation constants of modes of the corresponding complex optical potential are real. A class of such waveguides is found from a relation between two spectral problems. A particular example of an asymmetric waveguide, described by the hyperbolic functions, is analyzed. The existence and stability of linear modes and of continuous families of nonlinear modes are demonstrated. PMID- 25121691 TI - Resolution improvement in laser diode-based pump-probe microscopy with an annular pupil filter. AB - We experimentally demonstrate the use of annular beams to improve lateral resolution in laser-diode-based pump-probe microscopy. We found that the width of the point-spreading function in the case of the annular pump-probe beams is 162 nm, which is 30% smaller than that of the circular beams (232 nm). Furthermore, side lobes were efficiently suppressed at the focal plane since the pump-probe signal is proportional to the product of the two beam intensities. This scheme is demonstrated for the photothermal signal of nonfluorescent gold nanoparticles and the stimulated emission signal of fluorescence beads. PMID- 25121692 TI - Stable planar mesoscopic photonic crystal cavities. AB - Mesoscopic self-collimation (MSC) in mesoscopic photonic crystals with high reflectivity is exploited to realize a novel high Q-factor cavity by means of mesoscopic PhC planar mirrors. These mirrors efficiently confine a mode inside a planar Fabry-Perot-like cavity, that results from a beam focusing effect that stabilizes the cavity even for small beam sizes, resembling the focusing behavior of curved mirrors. Moreover, they show an improved reflectivity with respect to their standard distributed Bragg reflector counterparts that allows higher compactness. A Q-factor higher than 104 has been achieved for an optimized 5 period-long mirror cavity. The optimization of the Q-factor and the performances in terms of energy storage, field enhancement, and confinement are detailed. PMID- 25121693 TI - Optical injection unlocking for cavity ringdown spectroscopy. AB - Continuous wave cavity ringdown spectroscopy requires a rapid termination of the injection of light into the cavity to initiate the decay (i.e., ringdown) event. We demonstrate a technique that accomplishes this through pulsed optical injection of a second laser into the main laser, resulting in 20-100 MHz frequency shifts in the otherwise cavity-locked main laser sufficient to create ringdown events at 3.5 kHz. Data on the frequency shift as a function of both main laser current and relative wavelength are presented, as well as a demonstration that single exponential decays are maintained in the process. PMID- 25121694 TI - Nonlinear Raman-Nath diffraction of femtosecond laser pulses. AB - We study the nonlinear Raman-Nath diffraction (NRND) of femtosecond laser pulses in a 1D periodic nonlinear photonic structure. The calculated second-harmonic spectra represent frequency combs for different orders of transverse phase matching. These frequency combs are in close analogy with the well-known spectral Maker fringes observed in single crystals. The spectral intensity of the second harmonic experiences a redshift with a propagation angle, which is opposite the case of Cerenkov nonlinear diffraction. We analyze how NRND is affected by the group-velocity mismatch between fundamental and second-harmonic pulses and by the parameters of the structure. Our experimental results prove the theoretical predictions. PMID- 25121695 TI - Design of an efficient single photon source from a metallic nanorod dimer: a quasi-normal mode finite-difference time-domain approach. AB - We describe how the finite-difference time-domain (FDTD) technique can be used to compute the quasi-normal mode (QNM) for metallic nano-resonators, which is important for describing and understanding light-matter interactions in nanoplasmonics. We use the QNM to model the enhanced spontaneous emission rate for dipole emitters near a gold nanorod dimer structure using a newly developed QNM expansion technique. Enhanced single photon emission factors of around 1500 and output beta-factors of around 60% are found near the localized plasmon resonance. PMID- 25121696 TI - GHz bandwidth noise eater hybrid optical amplifier: design guidelines. AB - This Letter describes the design of an optical amplifier system optimized to reduce the relative intensity noise (RIN) of the input signal, and discloses its performance in terms of intensity noise reduction and bandwidth, without phase noise degradation. This polarization-maintaining amplifier is composed of an erbium-doped fiber amplifier (EDFA) cascaded with a semiconductor optical amplifier (SOA). The EDFA is sized to feed the SOA with a constant power corresponding to the optimal saturation level for noise reduction, through coherent population oscillations. When properly optimized, such an amplifier provides, simultaneously, 17 dB optical gain, 5.4 dB noise factor, and 20 dB reduction of the input-RIN across a 3 GHz bandwidth, without any electronics feedback loop. PMID- 25121697 TI - Incoherent-light temporal stretching of high-speed intensity waveforms. AB - We propose and demonstrate experimentally the first incoherent-light scheme for temporal imaging (magnification) of intensity waveforms. The scheme is based on a time-domain equivalent of a pinhole camera under incoherent illumination, involving two dispersive lines and temporal intensity modulation with a short gate. We report incoherent-light temporal stretching of radiofrequency waveforms by a magnification factor of 2.86, with a time-bandwidth product exceeding 160, i.e., a resolution of ~50 ps over a temporal aperture of ~8 ns, totally avoiding the use of chirp-controlled pulsed lasers. This work opens up new perspectives for realization of many critical high-speed signal-processing modules using practical incoherent light-wave schemes. PMID- 25121698 TI - Diode-pumped microchip Tm:KLu(WO4)2 laser with more than 3 W of output power. AB - A diode-pumped microchip laser containing a quasi-monolithic plano-plano cavity is realized on the basis of a Tm:KLu(WO4)2 crystal. The maximum CW output power is 3.2 W (at an absorbed pump power of 6.8 W) and the slope efficiency as high as 50.4%. The laser is operating at 1946 nm in the TEM00 mode with a M2<1.05. Microchip operation with Tm:KLu(WO4)2 is, in principle, due to a special crystal cut along the N(g) optical indicatrix axis. This crystal cut possesses positive near-spherical thermal lens that provides the required mode stabilization in the plano-plano cavity. Sensitivity factors of the thermal lens, "generalized" thermo optic coefficients and constants describing the photoelastic effect are determined for the monolithic Tm:KLu(WO4)2 crystal. PMID- 25121699 TI - Method for refractive index measurement of nanoparticles. AB - A new method of measuring the refractive indices of nanoparticles has been proposed based on refractive index matching between nanoparticles and surrounding organic solvents. By finding the most transparent point of the transmittance spectrum, the refractive index of the nanoparticles is equal to that of the solvents at the corresponding wavelength. Utilizing a Rayleigh scattering model, the effects of refractive index mismatching (Deltan) on the transmittance are investigated under different conditions. Some criteria for getting highly transparent nanoparticle dispersion and accurate refractive index measurements are suggested, which can support practical applications for nanomaterials in optical and optoelectronic applications. PMID- 25121700 TI - 1 Gbps directed optical decoder based on two cascaded microring resonators. AB - We report an electro-optic directed optical decoder based on two cascaded microring resonators (MRRs). PN junctions embedded around the MRRs are employed to modulate the MRRs through the carrier-injection scheme. The optical decoding function from a 2-bit electrical signal to a 4-bit optical signal at the speed of 1 Gbps is performed successfully by the device. PMID- 25121701 TI - Flexible picosecond thulium-doped fiber laser using the active mode-locking technique. AB - An all-fiber actively mode-locked thulium-doped fiber laser (AML-TDFL) based on a 10 GHz bandwidth electro-optic intensity modulator (EOM) providing flexible picosecond pulses at 1980 nm is presented. The EOM is driven by electrical pulses rather than traditional sine-wave signals. The repetition rate of output pulses was 21.4 MHz at fundamental mode-locking, which could be scaled up to 1.498 GHz through the 70th order harmonic mode-locking, and the shortest measured output pulse width was 38 ps. Furthermore, the output pulse width could be tuned by either adjusting the modulation frequency with small detuning or changing the width of these driving electrical pulses without frequency detuning. In our work, the stability of these mode-locked pulses obtained from the AML-TDFL was superior; for instance, the measured supermode suppression ratio of 1.498 GHz pulses train was up to 48 dB. PMID- 25121702 TI - Holographic patterning of graphene-oxide films by light-driven reduction. AB - We report on the patterning and reduction of graphene-oxide films by holographic lithography. Light reduction can be used to engineer low-cost graphene-based devices by performing a local conversion of insulating oxide into the conductive graphene. In this work, computer-generated holograms have been exploited to realize complex graphene patterns in a single shot, different from serial laser writing or mask-based photolithographic processes. The technique has been further improved by achieving speckle noise reduction: submicron and diffraction-limited features have been obtained. In addition we have also demonstrated that the gray scale lithography capability can be used to obtain different reduction levels in a single exposure. PMID- 25121703 TI - Optical microscope for three-dimensional surface displacement and shape measurements at the microscale. AB - We report a novel optical microscope for full-field, noncontact measurements of three-dimensional (3D) surface deformation and topography at the microscale. The microscope system is based on a seamless integration of the diffraction-assisted image correlation (DAIC) method with fluorescent microscopy. We experimentally demonstrate the microscope's capability for 3D measurements with submicrometer spatial resolution and subpixel measurement accuracy. PMID- 25121704 TI - A Raman waveplate for spinor Bose-Einstein condensates. AB - We demonstrate a waveplate for a pseudo-spin-1/2 Bose-Einstein condensate (BEC) using a two-photon Raman interaction. The angle of the waveplate is set by the relative phase of the optical fields, and the retardance is controlled by the pulse area. The waveplate allows us to image maps of the Stokes parameters of a BEC and thereby measure its relative ground-state phase. We demonstrate the waveplate by measuring the Stokes parameters of a coreless vortex. PMID- 25121705 TI - Heterodyne-detected and ultrafast time-resolved second-harmonic generation for sensitive measurements of charge transfer. AB - In organic photovoltaics many key ultrafast processes occur at the interface between electron donor and acceptor molecules. Traditional ultrafast spectroscopies, such as pump-probe or time-resolved fluorescence, are not ideal for studying the interface because most of their signal is from the bulk material. Time-resolved second-harmonic generation (TRSHG) spectroscopy solves this problem by only generating signal from the interface. We demonstrate an optically heterodyned TRSHG to reduce the impact of stray light, enhance sensitivity, and detect the full complex signal field. PMID- 25121706 TI - In situ detection of laser-induced slip initiation on the silicon wafer surface. AB - We propose a real-time in situ method to detect slip initiation on the surface of silicon wafers during high-power laser beam irradiation. In this method, light is collected from the surface of a silicon wafer subjected to laser irradiation. When the slip is initiated, it strongly scatters the laser beam, allowing detection of the time of the slip initiation based on the resulting sudden increase in the scattering signal. To demonstrate the performance of this method, a silicon wafer specimen was illuminated by a near-infrared continuous-wave fiber laser beam (of wavelength 1070 nm) at four different laser powers, and the scattered light was detected. The scattering signal increased suddenly at the time of slip initiation. To confirm the occurrence of slip, the surface morphologies of the silicon specimens after laser irradiation were analyzed using an optical microscope; surface slips were observed only in the specimens for which the sudden increase in scattering had been detected. Thus, the proposed method is shown to be very effective for the real-time in situ detection of surface slip initiation induced by high-power laser beam irradiation on silicon wafers. PMID- 25121707 TI - Experimental study on the dynamics of polarized strong optical injection in 1550 nm VCSELs. AB - We have experimentally analyzed the dynamics of polarized strong optical injection in 1550 nm vertical-cavity surface-emitting lasers (VCSELs). The locking ranges of optical injection-locked (OIL) VCSELs are experimentally measured in different states of polarized strong optical injection. Based on our novel ellipse model, the influence of the polarization state of strong injection light is quantitatively studied for the first time. PMID- 25121708 TI - Radiologic Manifestations of Senile Lymph Nodes in the Popliteal Fossa. AB - PURPOSE: To determine the radiologic manifestations of senile lymph nodes in the popliteal fossa for radiologic and clinical application. METHODS: A total of six lower extremities from four unembalmed human cadavers were studied. Under a surgical microscope, 6% hydrogen peroxide was used to detect the lymphatic vessels commencing from the foot and leg. A 30-gauge needle was inserted into the vessels and injected with a radio-opaque lead oxide mixture. The specimens were radiographed and photographed to demonstrate the lymph nodes in the popliteal fossa. The final results were transferred to the computer for image analysis. RESULTS: An average of two lymph nodes (range 1 to 3) were found in the popliteal fossa of the lower extremity. They were divided into superficial and deep popliteal groups. The superficial group was located in the superficial layer of the popliteal fossa around the small saphenous vein (SSV). The deep group was close to the popliteal surface of the femur and always located next to the popliteal vein. All lymph nodes were transparent in appearance and contained coiled lymphatic tubules. The size and density of the tubules varied. CONCLUSION: The radiologic manifestations of senile lymph nodes in the popliteal fossa have been presented and discussed to upgrade our radiologic and anatomical knowledge. This will be of benefit for radiologic and clinical applications. PMID- 25121709 TI - Enhancing Gibbs sampling method for motif finding in DNA with initial graph representation of sequences. AB - Finding short patterns with residue variation in a set of sequences is still an open problem in genetics, since motif-finding techniques on DNA and protein sequences are inconclusive on real data sets and their performance varies on different species. Hence, finding new algorithms and evolving established methods are vital to further understanding of genome properties and the mechanisms of protein development. In this work, we present an approach to finding functional motifs in DNA sequences in connection to Gibbs sampling method. Starting points in the search space are partly determined via graphical representation of input sequences opposed to completely random initial points with the standard Gibbs sampling. Our algorithm is evaluated on synthetic as well as on real data sets by using several statistics, such as sensitivity, positive predictive value, specificity, performance, and correlation coefficient. Additionally, a comparison between our algorithm and the basic standard Gibbs sampling algorithm is made to show improvement in accuracy, repeatability, and performance. PMID- 25121710 TI - Health department use of social media to identify foodborne illness - Chicago, Illinois, 2013-2014. AB - An estimated 55 million to 105 million persons in the United States experience acute gastroenteritis caused by foodborne illness each year, resulting in costs of $2-$4 billion annually. Many persons do not seek treatment, resulting in underreporting of the actual number of cases and cost of the illnesses. To prevent foodborne illness, local health departments nationwide license and inspect restaurants and track and respond to foodborne illness complaints. New technology might allow health departments to engage with the public to improve foodborne illness surveillance. For example, the New York City Department of Health and Mental Hygiene examined restaurant reviews from an online review website to identify foodborne illness complaints. On March 23, 2013, the Chicago Department of Public Health (CDPH) and its civic partners launched FoodBorne Chicago, a website (https://www.foodbornechicago.org) aimed at improving food safety in Chicago by identifying and responding to complaints on Twitter about possible foodborne illnesses. In 10 months, project staff members responded to 270 Twitter messages (tweets) and provided links to the FoodBorne Chicago complaint form. A total of 193 complaints of possible foodborne illness were submitted through FoodBorne Chicago, and 133 restaurants in the city were inspected. Inspection reports indicated 21 (15.8%) restaurants failed inspection, and 33 (24.8%) passed with conditions indicating critical or serious violations. Eight tweets and 19 complaint forms to FoodBorne Chicago described seeking medical treatment. Collaboration between public health professionals and the public via social media might improve foodborne illness surveillance and response. CDPH is working to disseminate FoodBorne Chicago via freely available open source software. PMID- 25121711 TI - Sugar-sweetened beverage consumption among adults -- 18 states, 2012. AB - Reducing consumption of calories from added sugars is a recommendation of the 2010 Dietary Guidelines for Americans and an objective of Healthy People 2020. Sugar-sweetened beverages (SSB) are major sources of added sugars in the diets of U.S. residents. Daily SSB consumption is associated with obesity and other chronic health conditions, including diabetes and cardiovascular disease. U.S. adults consumed an estimated average of 151 kcal/day of SSB during 2009-2010, with regular (i.e., nondiet) soda and fruit drinks representing the leading sources of SSB energy intake. However, there is limited information on state specific prevalence of SSB consumption. To assess regular soda and fruit drink consumption among adults in 18 states, CDC analyzed data from the 2012 Behavioral Risk Factor Surveillance System (BRFSS). Among the 18 states surveyed, 26.3% of adults consumed regular soda or fruit drinks or both >=1 times daily. By state, the prevalence ranged from 20.4% to 41.4%. Overall, consumption of regular soda or fruit drinks was most common among persons aged 18-34 years (24.5% for regular soda and 16.6% for fruit drinks), men (21.0% and 12.3%), non-Hispanic blacks (20.9% and 21.9%), and Hispanics (22.6% and 18.5%). Persons who want to reduce added sugars in their diets can decrease their consumption of foods high in added sugars such as candy, certain dairy and grain desserts, sweetened cereals, regular soda, fruit drinks, sweetened tea and coffee drinks, and other SSBs. States and health departments can collaborate with worksites and other community venues to increase access to water and other healthful beverages. PMID- 25121712 TI - Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP) -- United States, 2014-15 influenza season. AB - This report updates the 2013 recommendations by the Advisory Committee on Immunization Practices (ACIP) regarding use of seasonal influenza vaccines. Updated information for the 2014-15 influenza season includes 1) antigenic composition of U.S. seasonal influenza vaccines; 2) vaccine dose considerations for children aged 6 months through 8 years; and 3) a preference for the use, when immediately available, of live attenuated influenza vaccine (LAIV) for healthy children aged 2 through 8 years, to be implemented as feasible for the 2014-15 season but not later than the 2015-16 season. Information regarding issues related to influenza vaccination not addressed in this report is available in the 2013 ACIP seasonal influenza recommendations. PMID- 25121713 TI - Notes from the field: hospitalizations for respiratory disease among unaccompanied children from Central America - multiple States, June-July 2014. AB - During October 2013-June 2014, approximately 54,000 unaccompanied children, mostly from the Central American countries of El Salvador, Guatemala, and Honduras, were identified attempting entry into the United States from Mexico, exceeding numbers reported in previous years. Once identified in the United States, U.S. Customs and Border Protection, an agency of the U.S. Department of Homeland Security, processes the unaccompanied children and transfers them to the Office of Refugee Resettlement (ORR), an office of the Administration for Children and Families, U.S. Department of Health and Human Services. ORR cares for the children in shelters until they can be released to a sponsor, typically a parent or relative, who can care for the child while their immigration case is processed. In June 2014, in response to the increased number of unaccompanied children, U.S. Customs and Border Protection expanded operations to accommodate children at a processing center in Nogales, Arizona. ORR, together with the U.S. Department of Defense, opened additional large temporary shelters for the children at Lackland Air Force Base, Texas; U.S. Army Garrison Ft. Sill, Oklahoma; and Naval Base Ventura County, California. PMID- 25121714 TI - Notes from the field: malnutrition and elevated mortality among refugees from South Sudan - Ethiopia, June-July 2014. AB - As a result of armed civil conflict in South Sudan that started in mid-December of 2013, an estimated 1.1 million persons were internally displaced, and approximately 400,000 refugees fled South Sudan to neighboring countries (primarily to Ethiopia, Uganda, Sudan, and Kenya). Refugees from South Sudan arriving in Ethiopia are sheltered in three refugee camps located in Gambella region: Leitchuor, Kule, and Tierkidi. The camps were established during January May 2014 and have estimated refugee populations of 47,000, 51,000, and 50,000, respectively. Reports from health clinics and humanitarian agencies providing assistance to refugees suggested poor nutritional status of arriving refugees and elevated mortality rates. To assess the nutritional status of refugee children aged 6-59 months and mortality rates (crude [all ages] and aged <5 years), the Administration for Refugee and Returnee Affairs (an Ethiopian government aid agency), the United Nations High Commissioner for Refugees, World Food Programme, and United Nations Children's Fund, in collaboration with CDC, conducted cross sectional population-representative surveys in Leitchuor, Kule, and Tierkidi camps during June-July 2014. Anthropometric measurements in children were taken using standard procedures, and nutritional status was classified based on 2006 World Health Organization (WHO) growth standards. Hemoglobin was measured using HemoCue Hb 301. Anemia was diagnosed according to WHO thresholds. Retrospective mortality rates in Leitchuor and Kule were measured using a household census method. PMID- 25121715 TI - Alginate gelation-induced cell death during laser-assisted cell printing. AB - Modified laser-induced forward transfer has emerged as a promising bioprinting technique. Depending on the operating conditions and cell properties, laser cell printing may cause cell injury and even death, which should be carefully elucidated for it to be a viable technology. This study has investigated the effects of alginate gelation, gelation time, alginate concentration, and laser fluence on the post-transfer cell viability of NIH 3T3 fibroblasts. Sodium alginate and calcium chloride are used as the gel precursor and gel reactant solution to form cell-laden alginate microspheres. It is found that the effects of gelation depend on the duration of gelation. Two-minute gelation is observed to increase the cell viability after 24 h incubation, mainly due to the protective cushion effect of the forming gel membrane during droplet landing. Despite the cushion effect from 10 min gelation, it is observed that the cell viability decreases after 24 h incubation because of the forming thick gel membrane that reduces nutrient and oxygen diffusion from the culture medium. In addition, the cell viability after 24 h incubation decreases as the laser fluence or alginate concentration increases. PMID- 25121716 TI - Binding of a monoclonal antibody to the phospholamban cytoplasmic domain interferes with the channel activity of phospholamban reconstituted in a tethered bilayer lipid membrane. AB - Phospholamban (PLN), a membrane protein present in the sarcoplasmic reticulum of cardiac myocytes, is a crucial regulator of cardiac function. It is known that PLN appears as a monomer and as a pentamer. However, the role of the PLN pentamer and its ability to generate an ion channel are a matter of debate. To address this issue we employed an experimental approach that combines electrochemical impedance spectroscopy and surface plasmon resonance measurements. In particular, we investigated the channel activity of wild-type PLN reconstituted in a tethered bilayer lipid membrane (tBLM) on a gold surface. Our results indicate that reconstituted PLN can generate ion-conducting channels in a tBLM. Experiments with a PLN monoclonal antibody support an oriented incorporation of PLN in the tBLM. We show that the binding of the antibody to the PLN cytoplasmic domain interferes with PLN channel activity. PMID- 25121717 TI - A DFT study on the reaction mechanism of dimerization of methyl methacrylate catalyzed by N-heterocyclic carbene. AB - Reaction mechanisms of the N-heterocyclic carbene (NHC)-catalyzed dimerization of methyl methacrylate were studied using density functional theory (DFT) at the M05 2X/6-31G(d,p) level of theory. Four possible reaction channels (A, B, C, and D) have been investigated in this work. Particularly, we proposed a novel reaction pathway, where the proton transfers are assisted by a different molecule. The calculated results indicate that the channels B and D are more energetically favourable channels. The obtained results suggest that the E-isomer product is the main product, which is in agreement with the experimental results. Further calculations and analyses of global and local reactivity indices reveal the role of the NHC catalysts in the title reaction. The mechanistic insights gained are valuable for not only rational design of more efficient NHC catalysts but also for understanding the similar reaction mechanism. PMID- 25121718 TI - Trimethyltin-mediated covalent gold-carbon bond formation. AB - We study the formation of covalent gold-carbon bonds in benzyltrimethylstannane (C10H16Sn) deposited on Au in ultra-high-vacuum conditions. Through X-ray photoemission spectroscopy and X-ray absorption measurements, we find that the molecule fragments at the Sn-benzyl bond when exposed to Au surfaces at temperatures as low as -110 degrees C. The resulting benzyl species is stabilized by the presence of Au(111) but only forms covalent Au-C bonds on more reactive Au surfaces like Au(110). We also present spectroscopic proof for the existence of an electronic "gateway" state localized on the Au-C bond that is responsible for its unique electronic properties. Finally, we use DFT-based nudged elastic band calculations to elucidate the crucial role played by the under-coordinated Au surface in the formation of Au-C bonds. PMID- 25121721 TI - Rapid spectrophotometric method for determining surface free energy of microalgal cells. AB - Microalgae are one of the most promising renewable energy sources with environmental sustainability. The surface free energy of microalgal cells determines their biofouling and bioflocculation behavior and hence plays an important role in microalgae cultivation and harvesting. To date, the surface energetic properties of microalgal cells are still rarely studied. We developed a novel spectrophotometric method for directly determining the surface free energy of microalgal cells. The principles of this method are based on analyzing colloidal stability of microalgae suspensions. We have shown that this method can effectively differentiate the surface free energy of four microalgal strains, i.e., marine Chlorella sp., marine Nannochloris oculata, freshwater autotrophic Chlorella sp., and freshwater heterotrophic Chlorella sp. With advantages of high throughput and simplicity, this new spectrophotometric method has the potential to evolve into a standard method for measuring the surface free energy of cells and abiotic particles. PMID- 25121719 TI - Leukocyte activity in patients with ST-segment elevation acute myocardial infarction treated with anakinra. AB - Anakinra, the recombinant form of the human interleukin (IL)-1 receptor antagonist, blunts the acute systemic inflammatory response in patients with ST segment elevation myocardial infarction (STEMI), by determining a fall in peripheral blood leukocyte and plasma C-reactive protein levels. The aim of the present study was to determine the effects of anakinra on the activity of leukocytes measured ex vivo. Blood was collected 72 h after admission in 17 patients enrolled in the Virginia Commonwealth University-Anakirna Remodeling Trial (2) (VCU-ART2) and randomly treated with anakinra (N=7) or placebo (N=10). Whole blood was cultured at 37 degrees C for 24 h to measure spontaneous production of IL-6 or stimulated with Escherichia coli lipopolysaccharide (LPS) for toll-like receptor (TLR)-4 or heat-killed Staphylococcus epidermidis (SE) for TLR-2 activation. The cultures of anakinra-treated patients produced significantly less IL-6 spontaneously (71 pg/mL [27-114]) compared with placebo treated patients (290 pg/mL [211-617], p=0.005). LPS- or SE-induced IL-6 production, on the other hand, was not statistically different between anakinra versus placebo-treated patients (344 pg/mL [94-560] versus 370 pg/mL [306-991], p=0.32 for LPS, and 484 pg/mL [77-612] versus 615 pg/mL [413-871], p=0.31 for SE, respectively). IL-1 blockade with anakinra in STEMI patients results in reduced spontaneous leukocyte activity ex vivo without impairing the responsiveness to bacterial stimuli. PMID- 25121720 TI - The identification of perillyl alcohol glycosides with improved antiproliferative activity. AB - A facile route to perillyl alcohol (POH) differential glycosylation and the corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in vitro studies revealed a sugar dependent antiproliferative activity and the inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of representative POH glycosides. The most active glycoside from this cumulative study (4'-azido-d-glucoside, PG9) represents one of the most cytotoxic POH analogues reported to date. PMID- 25121722 TI - Low-cost motility tracking system (LOCOMOTIS) for time-lapse microscopy applications and cell visualisation. AB - Direct visualisation of cells for the purpose of studying their motility has typically required expensive microscopy equipment. However, recent advances in digital sensors mean that it is now possible to image cells for a fraction of the price of a standard microscope. Along with low-cost imaging there has also been a large increase in the availability of high quality, open-source analysis programs. In this study we describe the development and performance of an expandable cell motility system employing inexpensive, commercially available digital USB microscopes to image various cell types using time-lapse and perform tracking assays in proof-of-concept experiments. With this system we were able to measure and record three separate assays simultaneously on one personal computer using identical microscopes, and obtained tracking results comparable in quality to those from other studies that used standard, more expensive, equipment. The microscopes used in our system were capable of a maximum magnification of 413.6*. Although resolution was lower than that of a standard inverted microscope we found this difference to be indistinguishable at the magnification chosen for cell tracking experiments (206.8*). In preliminary cell culture experiments using our system, velocities (mean um/min +/- SE) of 0.81 +/- 0.01 (Biomphalaria glabrata hemocytes on uncoated plates), 1.17 +/- 0.004 (MDA-MB-231 breast cancer cells), 1.24 +/- 0.006 (SC5 mouse Sertoli cells) and 2.21 +/- 0.01 (B. glabrata hemocytes on Poly-L-Lysine coated plates), were measured and are consistent with previous reports. We believe that this system, coupled with open-source analysis software, demonstrates that higher throughput time-lapse imaging of cells for the purpose of studying motility can be an affordable option for all researchers. PMID- 25121724 TI - Endobronchial ultrasound elastography in the diagnosis of mediastinal and hilar lymph nodes. AB - OBJECTIVE: Endobronchial ultrasound elastography is a new technique for describing the stiffness of tissue during endobronchial ultrasound-guided transbronchial needle aspiration. The aims of this study were to evaluate the utility of endobronchial ultrasound elastography for mediastinal and hilar lymph nodes, and to compare the elastographic patterns of lymph nodes with results from endobronchial ultrasound-guided transbronchial needle aspiration. METHODS: Seventy-five lymph nodes were evaluated. A convex probe endobronchial ultrasound was used with a new endoscopic ultrasound processor to assess elastographic patterns that were classified based on color distribution as follows: Type 1, predominantly non-blue (green, yellow and red); Type 2, part blue, part non-blue (green, yellow and red); Type 3, predominantly blue. The elastographic patterns were compared with the final pathologic results from endobronchial ultrasound guided transbronchial needle aspiration. RESULTS: On pathological evaluation of the lymph nodes, 33 were benign and 42 were malignant. The lymph nodes that were classified as Type 1 on endobronchial ultrasound elastography were benign in 24/24 (100%); for Type 2 lymph nodes, 6/14 (46.9%) were benign and 8/14 (57.1%) were malignant; Type 3 lymph nodes were benign in 2/37 (5.4%) and malignant in 35/37 (94.6%). In classifying Type 1 as 'benign' and Type 3 as 'malignant,' the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy rates were 100, 92.3, 94.6, 100 and 96.7%, respectively. CONCLUSIONS: Endobronchial ultrasound elastography of mediastinal and hilar lymph nodes is a noninvasive technique that can be performed reliably and may be helpful in the prediction of nodal metastasis during endobronchial ultrasound guided transbronchial needle aspiration. PMID- 25121725 TI - On resilience and acceptance in the transition to palliative care at the end of life. AB - Specialist palliative care is a prominent and expanding site of health service delivery, providing highly specialised care to people at the end of life. Its focus on the delivery of specialised life-enhancing care stands in contrast to biomedicine's general tendency towards life-prolonging intervention. This philosophical departure from curative or life-prolonging care means that transitioning patients can be problematic, with recent work suggesting a wide range of potential emotional, communication and relational difficulties for patients, families and health professionals. Yet, we know little about terminally ill patients' lived experiences of this complex transition. Here, through interviews with 40 inpatients in the last few weeks of life, we explore their embodied and relational experiences of the transition to inpatient care, including their accounts of an ethic of resilience in pre-palliative care and an ethic of acceptance as they move towards specialist palliative care. Exploring the relationship between resilience and acceptance reveals the opportunities, as well as the limitations, embedded in the normative constructs that inflect individual experience of this transition. This highlights a contradictory dynamic whereby participants' experiences were characterised by talk of initiating change, while also acquiescing to the terminal progression of their illness. PMID- 25121726 TI - Dynamic alignment of transtibial prostheses through visualization of socket reaction moments. AB - BACKGROUND AND AIM: Dynamic alignment of transtibial prostheses is generally performed based on visual interpretation of gait without the benefit of any kinetic analysis in the clinic. The aim of this technical note was to present and discuss the possibilities of assisting dynamic alignment of transtibial prostheses through visualization of socket reaction moments. TECHNIQUE: Smart PyramidTM (currently EuropaTM) was used to measure the socket reaction moments under various alignment conditions from an amputee with transtibial prosthesis. The socket reaction moments were plotted to visualize the effect of alignment changes on them, and they were clinically interpreted. DISCUSSION: Socket reaction moments could complement information available to prosthetists to optimize prosthetic alignment. They could be used to reduce excessive loading on sensitive areas, to improve gait stability, or to communicate the outcome of dynamic alignment with the amputees. Further research is needed to identify the contribution of kinematics and kinetics for optimal alignment. CLINICAL RELEVANCE: Dynamic alignment of transtibial prostheses is currently tuned subjectively based on prosthetists' experiences and skills. Socket reaction moments may potentially provide objective information for prosthetists to align transtibial prostheses in the clinic. PMID- 25121727 TI - Collaboration between medical and veterinary professions on the problem of dog bites. PMID- 25121728 TI - Hematology as a diagnostic tool in bovine medicine. AB - The objective of the current review is to provide the reader with an overview of the bovine hematological profile. Sample collection, bovine reference ranges, and cattle-specific characteristics of erythrocyte, leukocyte, and platelet parameters are reviewed. Furthermore, diseases associated with abnormalities in the complete blood cell count of cattle are discussed. PMID- 25121730 TI - Systematic comparison of non-invasive measures for the assessment of atrial fibrillation complexity: a step forward towards standardization of atrial fibrillation electrogram analysis. AB - AIMS: To present a comparison of electrocardiogram-based non-invasive measures of atrial fibrillation (AF) substrate complexity computed on invasive animal recordings to discriminate between short-term and long-term AF. The final objective is the selection of an optimal sub-set of measures for AF complexity assessment. METHODS AND RESULTS: High-density epicardial direct contact mapping recordings (234 leads) were acquired from the right and the left atria of 17 goats in which AF was induced for 3 weeks (short-term AF group, N = 10) and 6 months (long-term AF group, N = 7). Several non-invasive measures of AF organization proposed in the literature in the last decade were investigated to assess their power in discriminating between the short-term and long-term group. The best performing measures were identified, which when combined attained a correct classification rate of 100%. Their ability to predict standard invasive AF complexity measures was also tested, showing an average R(2) of 0.73 +/- 0.04. CONCLUSION: An optimal set of measures of the AF substrate complexity was identified out of the set of non-invasive measures analysed in this study. These measures may contribute to improve patient-tailored diagnosis and therapy of sustained AF. PMID- 25121729 TI - PDGF-BB does not accelerate healing in diabetic mice with splinted skin wounds. AB - Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered to accelerate tissue repair of impaired chronic wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied PDGF-BB, we used a controlled full thickness splinted excisional wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined silicone splinted wound model, with reduced wound contraction, controlled splint and bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice. Wounds were topically treated once daily with either 3 ug PDGF-BB in 30 ul of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound contraction, wound closure, reepithelialization, collagen content, and wound bed inflammation were evaluated clinically and histopathologically. The bioactivity of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted wound model. Considering that the predominant mechanism of wound healing in humans is by re-epithelialization, the most appropriate model for evaluating therapeutics is one that uses splints to prevent excessive wound contraction. Here, we report that PDGF-BB does not promote wound closure by re epithelialization in a murine splinted wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the wound model used. PMID- 25121732 TI - Six in 10 doctors in Scotland plan to vote against independence. PMID- 25121734 TI - One-dimensional titanium dioxide nanomaterials: nanotubes. PMID- 25121731 TI - Nitric oxide from IFNgamma-primed macrophages modulates the antimicrobial activity of beta-lactams against the intracellular pathogens Burkholderia pseudomallei and Nontyphoidal Salmonella. AB - Our investigations show that nonlethal concentrations of nitric oxide (NO) abrogate the antibiotic activity of beta-lactam antibiotics against Burkholderia pseudomallei, Escherichia coli and nontyphoidal Salmonella enterica serovar Typhimurium. NO protects B. pseudomallei already exposed to beta-lactams, suggesting that this diatomic radical tolerizes bacteria against the antimicrobial activity of this important class of antibiotics. The concentrations of NO that elicit antibiotic tolerance repress consumption of oxygen (O2), while stimulating hydrogen peroxide (H2O2) synthesis. Transposon insertions in genes encoding cytochrome c oxidase-related functions and molybdenum assimilation confer B. pseudomallei a selective advantage against the antimicrobial activity of the beta-lactam antibiotic imipenem. Cumulatively, these data support a model by which NO induces antibiotic tolerance through the inhibition of the electron transport chain, rather than by potentiating antioxidant defenses as previously proposed. Accordingly, pharmacological inhibition of terminal oxidases and nitrate reductases tolerizes aerobic and anaerobic bacteria to beta-lactams. The degree of NO-induced beta-lactam antibiotic tolerance seems to be inversely proportional to the proton motive force (PMF), and thus the dissipation of DeltaH+ and DeltaPsi electrochemical gradients of the PMF prevents beta-lactam mediated killing. According to this model, NO generated by IFNgamma-primed macrophages protects intracellular Salmonella against imipenem. On the other hand, sublethal concentrations of imipenem potentiate the killing of B. pseudomallei by NO generated enzymatically from IFNgamma-primed macrophages. Our investigations indicate that NO modulates the antimicrobial activity of beta lactam antibiotics. PMID- 25121735 TI - Subverting ER-stress towards apoptosis by nelfinavir and curcumin coexposure augments docetaxel efficacy in castration resistant prostate cancer cells. AB - Despite its side-effects, docetaxel (DTX) remains a first-line treatment against castration resistant prostate cancer (CRPC). Therefore, strategies to increase its anti-tumor efficacy and decrease its side effects are critically needed. Targeting of the constitutive endoplasmic reticulum (ER) stress in cancer cells is being investigated as a chemosensitization approach. We hypothesized that the simultaneous induction of ER-stress and suppression of PI3K/AKT survival pathway will be a more effective approach. In a CRPC cell line, C4-2B, we observed significant (p<0.005) enhancement of DTX-induced cytotoxicity following coexposure to thapsigargin and an AKT-inhibitor. However, since these two agents are not clinically approved, we investigated whether a combination of nelfinavir (NFR) and curcumin (CUR), known to target both these metabolic pathways, can similarly increase DTX cytotoxicity in CRPC cells. Within 24 hrs post-exposure to physiologic concentrations of NFR (5 uM) and CUR (5 uM) a significantly (p<0.005) enhanced cytotoxicity was evident with low concentration of DTX (10 nM). This 3 drug combination rapidly increased apoptosis in aggressive C4-2B cells, but not in RWPE-1 cells or in primary prostate epithelial cells (PrEC). Comparative molecular studies revealed that this 3-drug combination caused a more pronounced suppression of phosphorylated-AKT and higher induction in phosphorylated eIF2alpha in C4-2B cells, as compared to RWPE-1 cells. Acute exposure (3-9 hrs) to this 3-drug combination intensified ER-stress induced pro-apoptotic markers, i.e. ATF4, CHOP, and TRIB3. At much lower concentrations, chronic (3 wks) exposures to these three agents drastically reduced colony forming units (CFU) by C4-2B cells. In vivo studies using mice containing C4-2B tumor xenografts showed significant (p<0.05) enhancement of DTX's (10 mg/kg) anti-tumor efficacy following coexposure to NFR (20 mg/kg) & CUR (100 mg/kg). Immunohistochemical (IHC) analyses of tumor sections indicated decreased Ki-67 staining and increased TUNEL intensity in mice exposed to the 3-drug combination. Therefore, subverting ER-stress towards apoptosis using adjuvant therapy with NFR and CUR can chemosensitize the CRPC cells to DTX therapy. PMID- 25121733 TI - Gene expansion shapes genome architecture in the human pathogen Lichtheimia corymbifera: an evolutionary genomics analysis in the ancient terrestrial mucorales (Mucoromycotina). AB - Lichtheimia species are the second most important cause of mucormycosis in Europe. To provide broader insights into the molecular basis of the pathogenicity associated traits of the basal Mucorales, we report the full genome sequence of L. corymbifera and compared it to the genome of Rhizopus oryzae, the most common cause of mucormycosis worldwide. The genome assembly encompasses 33.6 MB and 12,379 protein-coding genes. This study reveals four major differences of the L. corymbifera genome to R. oryzae: (i) the presence of an highly elevated number of gene duplications which are unlike R. oryzae not due to whole genome duplication (WGD), (ii) despite the relatively high incidence of introns, alternative splicing (AS) is not frequently observed for the generation of paralogs and in response to stress, (iii) the content of repetitive elements is strikingly low (<5%), (iv) L. corymbifera is typically haploid. Novel virulence factors were identified which may be involved in the regulation of the adaptation to iron limitation, e.g. LCor01340.1 encoding a putative siderophore transporter and LCor00410.1 involved in the siderophore metabolism. Genes encoding the transcription factors LCor08192.1 and LCor01236.1, which are similar to GATA type regulators and to calcineurin regulated CRZ1, respectively, indicating an involvement of the calcineurin pathway in the adaption to iron limitation. Genes encoding MADS-box transcription factors are elevated up to 11 copies compared to the 1-4 copies usually found in other fungi. More findings are: (i) lower content of tRNAs, but unique codons in L. corymbifera, (ii) Over 25% of the proteins are apparently specific for L. corymbifera. (iii) L. corymbifera contains only 2/3 of the proteases (known to be essential virulence factors) in comparison to R. oryzae. On the other hand, the number of secreted proteases, however, is roughly twice as high as in R. oryzae. PMID- 25121737 TI - A role for H2S in the microcirculation of newborns: the major metabolite of H2S (thiosulphate) is increased in preterm infants. AB - Excessive vasodilatation during the perinatal period is associated with cardiorespiratory instability in preterm neonates. Little evidence of the mechanisms controlling microvascular tone during circulatory transition exists. We hypothesised that hydrogen sulphide (H2S), an important regulator of microvascular reactivity and central cardiac function in adults and animal models, may contribute to the vasodilatation observed in preterm newborns. Term and preterm neonates (24-43 weeks gestational age) were studied. Peripheral microvascular blood flow was assessed by laser Doppler. Thiosulphate, a urinary metabolite of H2S, was determined by high performance liquid chromatography as a measure of 24 hr total body H2S turnover for the first 3 days of postnatal life. H2S turnover was greatest in very preterm infants and decreased with increasing gestational age (p = 0.0001). H2S turnover was stable across the first 72 hrs of life in older neonates. In very preterm neonates, H2S turnover increased significantly from day 1 to 3 (p =0.0001); and males had higher H2S turnover than females (p = 0.04). A significant relationship between microvascular blood flow and H2S turnover was observed on day 2 of postnatal life (p = 0.0004). H2S may play a role in maintaining microvascular tone in the perinatal period. Neonates at the greatest risk of microvascular dysfunction characterised by inappropriate peripheral vasodilatation--very preterm male neonates--are also the neonates with highest levels of total body H2S turnover suggesting that overproduction of this gasotransmitter may contribute to microvascular dysfunction in preterms. Potentially, H2S is a target to selectively control microvascular tone in the circulation of newborns. PMID- 25121736 TI - Diverse host-seeking behaviors of skin-penetrating nematodes. AB - Skin-penetrating parasitic nematodes infect approximately one billion people worldwide and are responsible for some of the most common neglected tropical diseases. The infective larvae of skin-penetrating nematodes are thought to search for hosts using sensory cues, yet their host-seeking behavior is poorly understood. We conducted an in-depth analysis of host seeking in the skin penetrating human parasite Strongyloides stercoralis, and compared its behavior to that of other parasitic nematodes. We found that Str. stercoralis is highly mobile relative to other parasitic nematodes and uses a cruising strategy for finding hosts. Str. stercoralis shows robust attraction to a diverse array of human skin and sweat odorants, most of which are known mosquito attractants. Olfactory preferences of Str. stercoralis vary across life stages, suggesting a mechanism by which host seeking is limited to infective larvae. A comparison of odor-driven behavior in Str. stercoralis and six other nematode species revealed that parasite olfactory preferences reflect host specificity rather than phylogeny, suggesting an important role for olfaction in host selection. Our results may enable the development of new strategies for combating harmful nematode infections. PMID- 25121738 TI - Combinatorial G-CSF/AMD3100 treatment in cardiac repair after myocardial infarction. AB - AIMS: Several studies suggest that circulating bone marrow derived stem cells promote the regeneration of ischemic tissues. For hematopoietic stem cell transplantation combinatorial granulocyte-colony stimulating factor (G CSF)/Plerixafor (AMD3100) administration was shown to enhance mobilization of bone marrow derived stem cells compared to G-CSF monotherapy. Here we tested the hypothesis whether combinatorial G-CSF/AMD3100 therapy has beneficial effects in cardiac recovery in a mouse model of myocardial infarction. METHODS: We analyzed the effect of single G-CSF (250 ug/kg/day) and combinatorial G-CSF/AMD3100 (100 ug/kg/day) treatment on cardiac morphology, vascularization, and hemodynamics 28 days after permanent ligation of the left anterior descending artery (LAD). G-CSF treatment started directly after induction of myocardial infarction (MI) for 3 consecutive days followed by a single AMD3100 application on day three after MI in the G-CSF/AMD3100 group. Cell mobilization was assessed by flow cytometry of blood samples drawn from tail vein on day 0, 7, and 14. RESULTS: Peripheral blood analysis 7 days after MI showed enhanced mobilization of white blood cells (WBC) and endothelial progenitor cells (EPC) upon G-CSF and combinatorial G-CSF/AMD3100 treatment. However, single or combinatorial treatment showed no improvement in survival, left ventricular function, and infarction size compared to the saline treated control group 28 days after MI. Furthermore, no differences in histology and vascularization of infarcted hearts could be observed. CONCLUSION: Although the implemented treatment regimen caused no adverse effects, our data show that combinatorial G-CSF/AMD therapy does not promote myocardial regeneration after permanent LAD occlusion. PMID- 25121740 TI - Microbial-derived butyrate: an oncometabolite or tumor-suppressive metabolite? AB - Dietary factors, microbial composition, and metabolism are intimately intertwined into a complex network whose activities influence important intestinal functions. In a recent issue of Cell, Belcheva et al. (2014) show that microbial-derived butyrate promotes proliferation of cancer-initiated intestinal epithelial cells, suggesting that it can act as an oncometabolite. PMID- 25121739 TI - CXCL12 induces connective tissue growth factor expression in human lung fibroblasts through the Rac1/ERK, JNK, and AP-1 pathways. AB - CXCL12 (stromal cell-derived factor-1, SDF-1) is a potent chemokine for homing of CXCR4+ fibrocytes to injury sites of lung tissue, which contributes to pulmonary fibrosis. Overexpression of connective tissue growth factor (CTGF) plays a critical role in pulmonary fibrosis. In this study, we investigated the roles of Rac1, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and activator protein-1 (AP-1) in CXCL12-induced CTGF expression in human lung fibroblasts. CXCL12 caused concentration- and time-dependent increases in CTGF expression and CTGF-luciferase activity. CXCL12-induced CTGF expression was inhibited by a CXCR4 antagonist (AMD3100), small interfering RNA of CXCR4 (CXCR4 siRNA), a dominant negative mutant of Rac1 (RacN17), a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor (PD98059), a JNK inhibitor (SP600125), a p21 activated kinase inhibitor (PAK18), c-Jun siRNA, and an AP-1 inhibitor (curcumin). Treatment of cells with CXCL12 caused activations of Rac1, Rho, ERK, and c-Jun. The CXCL12-induced increase in ERK phosphorylation was inhibited by RacN17. Treatment of cells with PD98059 and SP600125 both inhibited CXCL12 induced c-Jun phosphorylation. CXCL12 caused the recruitment of c-Jun and c-Fos binding to the CTGF promoter. Furthermore, CXCL12 induced an increase in alpha smooth muscle actin (alpha-SMA) expression, a myofibroblastic phenotype, and actin stress fiber formation. CXCL12-induced actin stress fiber formation and alpha-SMA expression were respectively inhibited by AMD3100 and CTGF siRNA. Taken together, our results suggest that CXCL12, acting through CXCR4, activates the Rac/ERK and JNK signaling pathways, which in turn initiates c-Jun phosphorylation, and recruits c-Jun and c-Fos to the CTGF promoter and ultimately induces CTGF expression in human lung fibroblasts. Moreover, overexpression of CTGF mediates CXCL12-induced alpha-SMA expression. PMID- 25121741 TI - What lies within: coinfections and immunity. AB - Helminth-induced immunomodulation is thought to influence the outcome of secondary infections. Osborne et al. (2014) and Reese et al. (2014) demonstrate that helminth infection impacts viral infections by tilting the immune system toward Th2/M2 immune regulatory responses that dampen Th1/M1 antiviral responses as well as promote reactivation of latent herpesviruses. PMID- 25121742 TI - Malaria parasite epigenetics: when virulence and romance collide. AB - Blood-stage malaria parasites evade the immune system by switching the protein exposed at the surface of the infected erythrocyte. A small proportion of these parasites commits to sexual development to mediate mosquito transmission. Two studies in this issue (Brancucci et al., 2014; Coleman et al., 2014) shed light on shared epigenetic machinery underlying both of these events. PMID- 25121743 TI - How a virus blocks a cellular emergency access lane to the nucleus, STAT! AB - Early in viral infection, the STAT1 transcription factor is rapidly transported into the nucleus using a nonconventional import mechanism to establish an antiviral state. In this issue, Xu et al. (2014) show how the Ebola virus VP24 protein precisely blocks specialized STAT1 import while leaving other cellular import processes intact. PMID- 25121744 TI - Getting rid of the bad apple: inflammasome-induced extrusion of Salmonella infected enterocytes. AB - Two reports in this issue of Cell Host & Microbe (Sellin et al., 2014; Knodler et al., 2014) establish the cell-intrinsic inflammasome-induced extrusion of infected enterocytes as a general defense mechanism against acute bacterial infections. PMID- 25121746 TI - Heterochromatin protein 1 secures survival and transmission of malaria parasites. AB - Clonally variant expression of surface antigens allows the malaria parasite Plasmodium falciparum to evade immune recognition during blood stage infection and secure malaria transmission. We demonstrate that heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, controls expression of numerous P. falciparum virulence genes as well as differentiation into the sexual forms that transmit to mosquitoes. Conditional depletion of P. falciparum HP1 (PfHP1) prevents mitotic proliferation of blood stage parasites and disrupts mutually exclusive expression and antigenic variation of the major virulence factor PfEMP1. Additionally, PfHP1-dependent regulation of PfAP2-G, a transcription factor required for gametocyte conversion, controls the switch from asexual proliferation to sexual differentiation, providing insight into the epigenetic mechanisms underlying gametocyte commitment. These findings show that PfHP1 is centrally involved in clonally variant gene expression and sexual differentiation in P. falciparum and have major implications for developing antidisease and transmission-blocking interventions against malaria. PMID- 25121745 TI - Collateral damage: microbiota-derived metabolites and immune function in the antibiotic era. AB - Our long-standing evolutionary association with gut-associated microbial communities has given rise to an intimate relationship, which affects many aspects of human health. Recent studies on the mechanisms that link these microbial communities to immune education, nutrition, and protection against pathogens point to microbiota-derived metabolites as key players during these microbe-host interactions. A disruption of gut-associated microbial communities by antibiotic treatment can result in a depletion of microbiota-derived metabolites, thereby enhancing pathogen susceptibility, impairing immune homeostasis, and contributing to the rise of certain chronic inflammatory diseases. Here, we highlight some of the recently elucidated mechanisms that showcase the impacts of microbiota-derived metabolites on human health. PMID- 25121747 TI - A Plasmodium falciparum histone deacetylase regulates antigenic variation and gametocyte conversion. AB - The asexual forms of the malaria parasite Plasmodium falciparum are adapted for chronic persistence in human red blood cells, continuously evading host immunity using epigenetically regulated antigenic variation of virulence-associated genes. Parasite survival on a population level also requires differentiation into sexual forms, an obligatory step for further human transmission. We reveal that the essential nuclear gene, P. falciparum histone deacetylase 2 (PfHda2), is a global silencer of virulence gene expression and controls the frequency of switching from the asexual cycle to sexual development. PfHda2 depletion leads to dysregulated expression of both virulence-associated var genes and PfAP2-g, a transcription factor controlling sexual conversion, and is accompanied by increases in gametocytogenesis. Mathematical modeling further indicates that PfHda2 has likely evolved to optimize the parasite's infectious period by achieving low frequencies of virulence gene expression switching and sexual conversion. This common regulation of cellular transcriptional programs mechanistically links parasite transmissibility and virulence. PMID- 25121748 TI - Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1. AB - During antiviral defense, interferon (IFN) signaling triggers nuclear transport of tyrosine-phosphorylated STAT1 (PY-STAT1), which occurs via a subset of karyopherin alpha (KPNA) nuclear transporters. Many viruses, including Ebola virus, actively antagonize STAT1 signaling to counteract the antiviral effects of IFN. Ebola virus VP24 protein (eVP24) binds KPNA to inhibit PY-STAT1 nuclear transport and render cells refractory to IFNs. We describe the structure of human KPNA5 C terminus in complex with eVP24. In the complex, eVP24 recognizes a unique nonclassical nuclear localization signal (NLS) binding site on KPNA5 that is necessary for efficient PY-STAT1 nuclear transport. eVP24 binds KPNA5 with very high affinity to effectively compete with and inhibit PY-STAT1 nuclear transport. In contrast, eVP24 binding does not affect the transport of classical NLS cargo. Thus, eVP24 counters cell-intrinsic innate immunity by selectively targeting PY STAT1 nuclear import while leaving the transport of other cargo that may be required for viral replication unaffected. PMID- 25121749 TI - HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells. AB - Immune evasion genes help human cytomegalovirus (HCMV) establish lifelong persistence. Without immune pressure, laboratory-adapted HCMV strains have undergone genetic alterations. Among these, the deletion of the UL/b' domain is associated with loss of virulence. In a screen of UL/b', we identified pUL135 as a protein responsible for the characteristic cytopathic effect of clinical HCMV strains that also protected from natural killer (NK) and T cell attack. pUL135 interacted directly with abl interactor 1 (ABI1) and ABI2 to recruit the WAVE2 regulatory complex to the plasma membrane, remodel the actin cytoskeleton and dramatically reduce the efficiency of immune synapse (IS) formation. An intimate association between F-actin filaments in target cells and the IS was dispelled by pUL135 expression. Thus, F-actin in target cells plays a critical role in synaptogenesis, and this can be exploited by pathogens to protect against cytotoxic immune effector cells. An independent interaction between pUL135 and talin disrupted cell contacts with the extracellular matrix. PMID- 25121750 TI - HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria. AB - Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B cells using recombinant antibody technology and probed their relationship to commensal bacteria. The dominant ileum B cell response was to Env gp41. Remarkably, a majority (82%) of the ileum anti-gp41 antibodies cross reacted with commensal bacteria, and of those, 43% showed non-HIV-1 antigen polyreactivity. Pyrosequencing revealed shared HIV-1 antibody clonal lineages between ileum and blood. Mutated immunoglobulin G antibodies cross-reactive with both Env gp41 and microbiota could also be isolated from the ileum of HIV-1 uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive antibodies originate in the intestine, and the gp41 Env response in HIV-1 infection can be derived from a preinfection memory B cell pool triggered by commensal bacteria that cross-react with Env. PMID- 25121751 TI - Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa. AB - The gut mucosal epithelium separates the host from the microbiota, but enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this barrier. Defenses against such acute insults remain incompletely understood. Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting pathogen loads in the epithelium during early infection. Although the epithelium invading S.Tm replicate initially, this intraepithelial replicative niche is restricted by expulsion of infected enterocytes into the lumen. This mechanism is compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are deleted, or ablated specifically in the epithelium, resulting in ~100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1alpha/beta and IL-18, appear dispensable for epithelial restriction of early infection. These data establish the role of an epithelium-intrinsic inflammasome, which drives expulsion of infected cells to restrict the pathogen's intraepithelial proliferation. This may represent a general defense mechanism against mucosal infections. PMID- 25121754 TI - Assessment of the relationship between nondipping phenomenon and microvolt T-wave alternans. AB - OBJECTIVE: The aim of this cross-sectional study was to evaluate microvolt T-wave alternans (MTWA) as a marker of myocardial electrical instability in normotensive and hypertensive individuals with either nondipper or dipper-type circadian rhythm of blood pressure. MATERIALS AND METHODS: The study group included a total of 181 patients: 118 hypertensive patients and 63 normotensive healthy volunteers [mean age 46 +/- 8; 34 men (54%)]. The patients with hypertension were divided into two groups on the basis of their results of 24-h ambulatory blood pressure monitoring: 61 patients with dipper hypertension [mean age 46 +/- 6; 32 men (52.5%)] and 57 patients with nondipper hypertension [mean age 48 +/- 10; 36 men (63.2%)]. The MTWAs of all patients were analyzed using the time-domain modified moving average method by means of a treadmill exercise stress test. RESULTS: MTWA positivity was statistically significantly different between all groups. Left ventricular mass index, E/E', interventricular septum, posterior wall, 24-h systolic blood pressure and diastolic blood pressure, and night-time systolic blood pressure and diastolic blood pressure were correlated positively with MTWA. Left ventricular mass index and the presence of nondipper hypertension were determined to be independent predictors of MTWA positivity. CONCLUSION: The blunting of the nocturnal decrease in blood pressure was associated with MTWA positivity in hypertensive patients. PMID- 25121753 TI - Hepatitis C virus subverts liver-specific miR-122 to protect the viral genome from exoribonuclease Xrn2. AB - The abundant, liver-specific microRNA miR-122 forms extensive base-pairing interactions with the 5' noncoding region of the hepatitis C virus (HCV) RNA genome, protecting the viral RNA from degradation. We discovered that the 5'-3' exoribonuclease Xrn2, which plays a crucial role in the transcription termination of RNA polymerase II, modulates HCV RNA abundance in the cytoplasm, but is counteracted by miR-122-mediated protection. Specifically, Xrn2 depletion results in increased accumulation of viral RNA, while Xrn2 overexpression diminishes viral RNA abundance. Depletion of Xrn2 did not alter translation or replication rates of HCV RNA, but affected viral RNA stability. Importantly, during sequestration of miR-122, Xrn2 depletion restored HCV RNA abundance, arguing that Xrn2 depletion eliminates the miR-122 requirement for viral RNA stability. Thus, Xrn2 has a cytoplasmic, antiviral function against HCV that is counteracted by HCV's subversion of miR-122 to form a protective oligomeric complex at the 5' end of the viral genome. PMID- 25121752 TI - Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. AB - Inflammasome-mediated host defenses have been extensively studied in innate immune cells. Whether inflammasomes function for innate defense in intestinal epithelial cells, which represent the first line of defense against enteric pathogens, remains unknown. We observed enhanced Salmonella enterica serovar Typhimurium colonization in the intestinal epithelium of caspase-11-deficient mice, but not at systemic sites. In polarized epithelial monolayers, siRNA mediated depletion of caspase-4, a human ortholog of caspase-11, also led to increased bacterial colonization. Decreased rates of pyroptotic cell death, a host defense mechanism that extrudes S. Typhimurium-infected cells from the polarized epithelium, accounted for increased pathogen burdens. The caspase-4 inflammasome also governs activation of the proinflammatory cytokine, interleukin (IL)-18, in response to intracellular (S. Typhimurium) and extracellular (enteropathogenic Escherichia coli) enteric pathogens, via intracellular LPS sensing. Therefore, an epithelial cell-intrinsic noncanonical inflammasome plays a critical role in antimicrobial defense at the intestinal mucosal surface. PMID- 25121755 TI - The effect of orthostatic stress type on cardiovascular control. AB - OBJECTIVES: We aimed to compare the cardiovascular responses of a novel orthostatic stress test, the passive seated orthostatic stress test (PSOST), with those during passive head-up tilt testing (HUTT). We hypothesized that cardiovascular responses during PSOST would be similar to those during HUTT (the 'gold standard'). METHODS: We tested 15 healthy volunteers, who underwent both PSOST and HUTT during one session in a random order. We measured beat-to-beat blood pressure, heart rate, peripheral resistance, stroke volume, cardiac output, and middle cerebral artery blood flow velocity during each test. RESULTS: Blood pressure responses were not significantly different between PSOST and HUTT, except for a significantly lower delayed nadir and 15-min recovery value in systolic arterial pressure during HUTT. HUTT elicited a significantly larger increase in heart rate during all test intervals in comparison with PSOST, as well as a larger decline in stroke volume during almost all test intervals. Responses for the other hemodynamic variables were not significantly different between the tests at any test interval. Repeated HUTT has large inherent variability, which was also evident from the variability in the mean differences on comparing PSOST and HUTT. There was a significant bias for larger heart rate increases (P<0.01) and a greater delayed systolic arterial pressure decline during HUTT. CONCLUSION: We have shown that PSOST and HUTT elicit similar blood pressure and cerebrovascular responses in the early stages of the upright phase. We believe that PSOST is a reasonable surrogate for HUTT in assessing orthostatic hypotension in population groups that are unable to stand for prolonged periods of time. PMID- 25121756 TI - Neck circumference and body mass index as independent predictors of hypertension misclassification in patients suspected of having obstructive sleep apnea. AB - OBJECTIVE(S): Twenty-four-hour ambulatory blood pressure monitoring (ABPM) seems to be the most accurate way of diagnosing hypertension in patients with obstructive sleep apnea (OSA). However, this diagnostic tool is expensive and time-consuming and is therefore not used routinely. We aimed to find baseline predictors that enable the identification of patients who misclassify themselves as nonhypertensive to optimize the use of ABPM. METHODS: Clinically suspected OSA patients (n=369) were enrolled and underwent overnight polysomnography and 24-h ABPM, and completed a data collection form. Anthropometric measurements were assessed. Generalized additive models, the minimum P-value approach, and logistic regression models were used for data analysis. Results were considered significant when alpha is equal to 0.05. RESULTS: One hundred and twenty-two patients who were not on antihypertensive medication did not report hypertension, but according to ABPM data, 43.4% (n=53) of them had misclassified themselves as nonhypertensive. These patients had a significantly higher apnea-hypopnea index (P<0.001), ABPM variables (P<0.001), BMI (P=0.002), and neck circumference (NC) (P=0.002) than nonhypertensive patients (n=69). BMI and NC emerged as independent predictors of hypertension misclassification. The cut-off points that best discriminated the two groups of patients were 27 kg/m and 39 cm for BMI and NC, respectively. The resulting binary BMI and NC remained independent predictors of hypertension misclassification in the final model (odds ratio: 3.2, P=0.010; odds ratio: 2.4, P=0.038). CONCLUSION: Our findings emphasize the importance of ABPM for the diagnosis of hypertension in patients suspected of having OSA with a BMI and NC above 27 kg/m and 39 cm, respectively. PMID- 25121757 TI - Transcriptome sequencing from diverse human populations reveals differentiated regulatory architecture. AB - Large-scale sequencing efforts have documented extensive genetic variation within the human genome. However, our understanding of the origins, global distribution, and functional consequences of this variation is far from complete. While regulatory variation influencing gene expression has been studied within a handful of populations, the breadth of transcriptome differences across diverse human populations has not been systematically analyzed. To better understand the spectrum of gene expression variation, alternative splicing, and the population genetics of regulatory variation in humans, we have sequenced the genomes, exomes, and transcriptomes of EBV transformed lymphoblastoid cell lines derived from 45 individuals in the Human Genome Diversity Panel (HGDP). The populations sampled span the geographic breadth of human migration history and include Namibian San, Mbuti Pygmies of the Democratic Republic of Congo, Algerian Mozabites, Pathan of Pakistan, Cambodians of East Asia, Yakut of Siberia, and Mayans of Mexico. We discover that approximately 25.0% of the variation in gene expression found amongst individuals can be attributed to population differences. However, we find few genes that are systematically differentially expressed among populations. Of this population-specific variation, 75.5% is due to expression rather than splicing variability, and we find few genes with strong evidence for differential splicing across populations. Allelic expression analyses indicate that previously mapped common regulatory variants identified in eight populations from the International Haplotype Map Phase 3 project have similar effects in our seven sampled HGDP populations, suggesting that the cellular effects of common variants are shared across diverse populations. Together, these results provide a resource for studies analyzing functional differences across populations by estimating the degree of shared gene expression, alternative splicing, and regulatory genetics across populations from the broadest points of human migration history yet sampled. PMID- 25121758 TI - Age and sex-specific relationships between phthalate exposures and obesity in Chinese children at puberty. AB - OBJECTIVE: To examine the age and sex-specific associations of urine levels of six mono-phthalates with body size and fat distribution in Chinese children at puberty. MATERIALS AND METHODS: Four hundred and ninety-three school-aged children (247 boys, 246 girls) were recruited. Obesity related anthropometric indices were measured and body fat proportion (BF%) was calculated. Spot urine samples were collected and phthalate monoesters were detected by an API 2000 electrospray triple quadrupole mass spectrometer (ESI-MS/MS). Associations between phthalate exposure and overweight/obesity measures and their trends were examined by multiple linear regression and Logistic regression analyses, respectively. RESULTS: Di-2-ethylhexyl phthalate (DEHP) metabolites and monobutyl phthalate (MBP) were found to be the most detectable chemicals. In 8-10 years (yrs) group, concentrations of MEHP and MBP were significantly higher in girls than those in boys. However, concentrations of all phthalate monoesters, except for MEP and MEHP, in 11-13 yrs boys were significantly higher than those in girls. After adjusting for confounders including puberty onset, urinary concentrations of MBP and sum of low molecular-weight phthalate metabolites (?LMP) were positively associated with boys' obesity in a concentration-effect manner, while concentrations of MEHP, MEHHP and sum of DEHP metabolites (?MEHP) were negatively associated with girls' obesity. Associations between phthalate exposure levels and BMI z-score changes were age- and sex-specific in school-age children. CONCLUSION: There are age and sex-specific concentration-effect associations between phthalate exposure and fat distribution in Chinese children. Urinary phthalate levels in 11-13 yrs boys were about 30 percent higher than those in girls, and ?MEHP levels in younger boys (<10 yrs) were significantly higher than those in elder boys (>10 yrs). Associations were positive for MBP and ?LMP with both BMI z-score and fat distribution in boys >10 years of age, and negative for ?MEHP with fat distribution in girls <10 years of age. PMID- 25121759 TI - Primary amoebic meningoencephalitis caused by Naegleria fowleri: an old enemy presenting new challenges. AB - First discovered in 1899, Naegleria fowleri is a protist pathogen, known to infect the central nervous system and produce primary amoebic meningoencephalitis. The most distressing aspect is that the fatality rate has remained more than 95%, despite our advances in antimicrobial chemotherapy and supportive care. Although rare worldwide, most cases have been reported in the United States, Australia, and Europe (France). A large number of cases in developing countries go unnoticed. In particular, religious, recreational, and cultural practices such as ritual ablution and/or purifications, Ayurveda, and the use of neti pots for nasal irrigation can contribute to this devastating infection. With increasing water scarcity and public reliance on water storage, here we debate the need for increased awareness of primary amoebic meningoencephalitis and the associated risk factors, particularly in developing countries. PMID- 25121760 TI - The rich get richer: brain injury elicits hyperconnectivity in core subnetworks. AB - There remains much unknown about how large-scale neural networks accommodate neurological disruption, such as moderate and severe traumatic brain injury (TBI). A primary goal in this study was to examine the alterations in network topology occurring during the first year of recovery following TBI. To do so we examined 21 individuals with moderate and severe TBI at 3 and 6 months after resolution of posttraumatic amnesia and 15 age- and education-matched healthy adults using functional MRI and graph theoretical analyses. There were two central hypotheses in this study: 1) physical disruption results in increased functional connectivity, or hyperconnectivity, and 2) hyperconnectivity occurs in regions typically observed to be the most highly connected cortical hubs, or the "rich club". The current findings generally support the hyperconnectivity hypothesis showing that during the first year of recovery after TBI, neural networks show increased connectivity, and this change is disproportionately represented in brain regions belonging to the brain's core subnetworks. The selective increases in connectivity observed here are consistent with the preferential attachment model underlying scale-free network development. This study is the largest of its kind and provides the unique opportunity to examine how neural systems adapt to significant neurological disruption during the first year after injury. PMID- 25121761 TI - Isolation of cancer stem cells from three human glioblastoma cell lines: characterization of two selected clones. AB - Cancer stem cells (CSC) were isolated via a non-adherent neurosphere assay from three glioma cell lines: LI, U87, and U373. Using a clonal assay, two clones (D2 and F11) were selected from spheres derived from LI cells and were characterized for the: expression of stem cell markers (CD133, Nestin, Musashi-1 and Sox2); proliferation; differentiation capability (determined by the expression of GalC, betaIII-Tubulin and GFAP); Ca(2+) signaling and tumorigenicity in nude mice. Both D2 and F11 clones expressed higher levels of all stem cell markers with respect to the parental cell line. Clones grew more slowly than LI cells with a two-fold increase in duplication time. Markers of differentiation (betaIII-Tubulin and GFAP) were expressed at high levels in both LI cells and in neurospheres. The expression of Nestin, Sox2, and betaIII-Tubulin was down-regulated in D2 and F11 when cultured in serum-containing medium, whereas Musashi-1 was increased. In this condition, duplication time of D2 and F11 increased without reaching that of LI cells. D2, F11 and parental cells did not express voltage-dependent Ca(2+) channels but they exhibited increased intracellular Ca(2+) levels in response to ATP. These Ca(2+) signals were larger in LI cells and in spheres cultured in serum-containing medium, while they were smaller in serum-free medium. The ATP treatment did not affect cell proliferation. Both D2 and F11 induced the appearance of tumors when ortotopically injected in athymic nude mice at a density 50-fold lower than that of LI cells. All these data indicate that both clones have characteristics of CSC and share the same stemness properties. The findings regarding the expression of differentiation markers and Ca(2+)-channels show that both clones are unable to reach the terminal differentiation. Both D2 and F11 might represent a good model to improve the knowledge on CSC in glioblastoma and to identify new therapeutic approaches. PMID- 25121762 TI - Unveiling time in dose-response models to infer host susceptibility to pathogens. AB - The biological effects of interventions to control infectious diseases typically depend on the intensity of pathogen challenge. As much as the levels of natural pathogen circulation vary over time and geographical location, the development of invariant efficacy measures is of major importance, even if only indirectly inferrable. Here a method is introduced to assess host susceptibility to pathogens, and applied to a detailed dataset generated by challenging groups of insect hosts (Drosophila melanogaster) with a range of pathogen (Drosophila C Virus) doses and recording survival over time. The experiment was replicated for flies carrying the Wolbachia symbiont, which is known to reduce host susceptibility to viral infections. The entire dataset is fitted by a novel quantitative framework that significantly extends classical methods for microbial risk assessment and provides accurate distributions of symbiont-induced protection. More generally, our data-driven modeling procedure provides novel insights for study design and analyses to assess interventions. PMID- 25121763 TI - Genetic diversity and structure of Dalmatian pyrethrum (Tanacetum cinerariifolium Trevir./Sch./Bip., Asteraceae) within the Balkan refugium. AB - Dalmatian pyrethrum (Tanacetum cinerariifolium Trevir./Sch./Bip.) is an outcrossing, perennial insecticidal plant, restricted to the eastern Adriatic coast (Mediterranean). Amplified fragment-length polymorphisms (AFLP) were used to investigate the genetic diversity and structure within and among 20 natural plant populations. The highest level of gene diversity, the number of private alleles and the frequency down-weighted marker values (DW) were found in northern Adriatic populations and gradually decreased towards the southern boundary of the species range. Genetic impoverishment of these southern populations is most likely the result of human-related activities. An analysis of molecular variance (AMOVA) indicated that most of the genetic diversity was attributed to differences among individuals within populations (85.78%), which are expected due to the outcrossing nature of the species. A Bayesian analysis of the population structure identified two dominant genetic clusters. A spatial analysis of the genetic diversity indicated that 5.6% of the genetic differentiation resulted from isolation by distance (IBD), while 12.3% of the genetic differentiation among populations followed the pattern of isolation by environmental distance (IBED). Knowledge of the genetic diversity patterns of the natural populations and the mechanism behind these patterns is required for the exploitation and possible conservation management of this endemic and economically important species. PMID- 25121766 TI - A deterministic model predicts the properties of stochastic calcium oscillations in airway smooth muscle cells. AB - The inositol trisphosphate receptor ([Formula: see text]) is one of the most important cellular components responsible for oscillations in the cytoplasmic calcium concentration. Over the past decade, two major questions about the [Formula: see text] have arisen. Firstly, how best should the [Formula: see text] be modeled? In other words, what fundamental properties of the [Formula: see text] allow it to perform its function, and what are their quantitative properties? Secondly, although calcium oscillations are caused by the stochastic opening and closing of small numbers of [Formula: see text], is it possible for a deterministic model to be a reliable predictor of calcium behavior? Here, we answer these two questions, using airway smooth muscle cells (ASMC) as a specific example. Firstly, we show that periodic calcium waves in ASMC, as well as the statistics of calcium puffs in other cell types, can be quantitatively reproduced by a two-state model of the [Formula: see text], and thus the behavior of the [Formula: see text] is essentially determined by its modal structure. The structure within each mode is irrelevant for function. Secondly, we show that, although calcium waves in ASMC are generated by a stochastic mechanism, [Formula: see text] stochasticity is not essential for a qualitative prediction of how oscillation frequency depends on model parameters, and thus deterministic [Formula: see text] models demonstrate the same level of predictive capability as do stochastic models. We conclude that, firstly, calcium dynamics can be accurately modeled using simplified [Formula: see text] models, and, secondly, to obtain qualitative predictions of how oscillation frequency depends on parameters it is sufficient to use a deterministic model. PMID- 25121765 TI - Mobility and generation of mosaic non-autonomous transposons by Tn3-derived inverted-repeat miniature elements (TIMEs). AB - Functional transposable elements (TEs) of several Pseudomonas spp. strains isolated from black shale ore of Lubin mine and from post-flotation tailings of Zelazny Most in Poland, were identified using a positive selection trap plasmid strategy. This approach led to the capture and characterization of (i) 13 insertion sequences from 5 IS families (IS3, IS5, ISL3, IS30 and IS1380), (ii) isoforms of two Tn3-family transposons--Tn5563a and Tn4662a (the latter contains a toxin-antitoxin system), as well as (iii) non-autonomous TEs of diverse structure, ranging in size from 262 to 3892 bp. The non-autonomous elements transposed into AT-rich DNA regions and generated 5- or 6-bp sequence duplications at the target site of transposition. Although these TEs lack a transposase gene, they contain homologous 38-bp-long terminal inverted repeat sequences (IRs), highly conserved in Tn5563a and many other Tn3-family transposons. The simplest elements of this type, designated TIMEs (Tn3 family derived Inverted-repeat Miniature Elements) (262 bp), were identified within two natural plasmids (pZM1P1 and pLM8P2) of Pseudomonas spp. It was demonstrated that TIMEs are able to mobilize segments of plasmid DNA for transposition, which results in the generation of more complex non-autonomous elements, resembling IS driven composite transposons in structure. Such transposon-like elements may contain different functional genetic modules in their core regions, including plasmid replication systems. Another non-autonomous element "captured" with a trap plasmid was a TIME derivative containing a predicted resolvase gene and a res site typical for many Tn3-family transposons. The identification of a portable site-specific recombination system is another intriguing example confirming the important role of non-autonomous TEs of the TIME family in shuffling genetic information in bacterial genomes. Transposition of such mosaic elements may have a significant impact on diversity and evolution, not only of transposons and plasmids, but also of other types of mobile genetic elements. PMID- 25121768 TI - Metabolome analysis of Drosophila melanogaster during embryogenesis. AB - The Drosophila melanogaster embryo has been widely utilized as a model for genetics and developmental biology due to its small size, short generation time, and large brood size. Information on embryonic metabolism during developmental progression is important for further understanding the mechanisms of Drosophila embryogenesis. Therefore, the aim of this study is to assess the changes in embryos' metabolome that occur at different stages of the Drosophila embryonic development. Time course samples of Drosophila embryos were subjected to GC/MS based metabolome analysis for profiling of low molecular weight hydrophilic metabolites, including sugars, amino acids, and organic acids. The results showed that the metabolic profiles of Drosophila embryo varied during the course of development and there was a strong correlation between the metabolome and different embryonic stages. Using the metabolome information, we were able to establish a prediction model for developmental stages of embryos starting from their high-resolution quantitative metabolite composition. Among the important metabolites revealed from our model, we suggest that different amino acids appear to play distinct roles in different developmental stages and an appropriate balance in trehalose-glucose ratio is crucial to supply the carbohydrate source for the development of Drosophila embryo. PMID- 25121767 TI - Bone morphogenetic protein 6 polymorphisms are associated with radiographic progression in ankylosing spondylitis. AB - BACKGROUND AND OBJECT: Nearly 25 genetic loci associated with susceptibility to ankylosing spondylitis (AS) have been identified by several large studies. However, there have been limited studies to identify the genes associated with radiographic severity of the disease. Thus we investigated which genes involved in bone formation pathways might be associated with radiographic severity in AS. METHODS: A total of 417 Korean AS patients were classified into two groups based on the radiographic severity as defined by the modified Stoke' Ankylosing Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone formation were selected and genotyped. Odds ratios (OR) and 95% confidence interval (95% CI) were analysed by multivariate logistic regression controlling for age at onset of symptoms, sex, disease duration, and smoking status as covariates. RESULTS: We identified new loci of bone morphogenetic protein 6 (BMP6) associated with radiographic severity in patients with AS that passed false discovery rate threshold. Two SNPs in BMP6 were significantly associated with radiologic severity [rs270378 (OR 1.97, p = 6.74 * 10(-4)) and rs1235192 [OR 1.92, p = 1.17 * 10(-3)]) adjusted by covariates. CONCLUSION: This is the first study to demonstrate that BMP6 is associated with radiographic severity in AS, supporting the role wingless-type like/BMP pathway on radiographic progression in AS. PMID- 25121769 TI - Adjuvant and salvage radiotherapy after prostatectomy: a systematic review and meta-analysis. AB - PURPOSE: In men with adverse prognostic factors (APFs) after radical prostatectomy (RP), the most appropriate timing to administer radiotherapy remains a subject for debate. We conducted a systemic review and meta-analysis to evaluate the therapeutic strategies: adjuvant radiotherapy (ART) and salvage radiotherapy (SRT). MATERIALS AND METHODS: We comprehensively searched PubMed, EMBASE, Web of Science and the Cochrane Library and performed the meta-analysis of all randomized controlled trials (RCTs) and retrospective comparative studies assessing the prognostic factors of ART and SRT. RESULTS: Between May 1998 and July 2012, 2 matched control studies and 16 retrospective studies including a total of 2629 cases were identified (1404 cases for ART and 1185 cases for SRT). 5-year biochemical failure free survival (BFFS) for ART was longer than that for SRT (Hazard Ratio [HR]: 0.37; 95% CI, 0.30-0.46; p<0.00001, I(2) = 0%). 3-year BFFS was significantly longer in the ART (HR: 0.38; 95% CI, 0.28-0.52; p<0.00001, I(2) = 0%). Overall survival (OS) was also better in the ART (RR: 0.53; 95% CI, 0.41-0.68; p<0.00001, I(2) = 0%), as did disease free survival (DFS) (RR: 0.53; 95% CI, 0.43-0.66; p<0.00001, I(2) = 0%). Exploratory subgroup analysis and sensitivity analysis revealed the similar results with original analysis. CONCLUSION: ART therapy offers a safe and efficient alternative to SRT with longer 3-year and 5-year BFFS, better OS and DFS. Our recommendation is to suggest ART for patients with APFs and may reduce the need for SRT. Given the inherent limitations of the included studies, future well-designed RCTs are awaited to confirm and update this analysis. PMID- 25121764 TI - Helicobacter pylori from gastric cancer and duodenal ulcer show same phylogeographic origin in the Andean region in Colombia. AB - BACKGROUND: A recent report has shown that the phylogenetic origin of Helicobacter pylori based on multi-locus sequence typing (MLST) was significantly associated with the severity of gastritis in Colombia. However, the potential relationship between phylogenetic origin and clinical outcomes was not examined in that study. If the phylogenetic origin rather than virulence factors were truly associated with clinical outcomes, identifying a population at high risk for gastric cancer in Colombia would be relatively straightforward. In this study, we examined the phylogenetic origins of strains from gastric cancer and duodenal ulcer patients living in Bogota, Colombia. METHODS: We included 35 gastric cancer patients and 31 duodenal ulcer patients, which are considered the variant outcomes. The genotypes of cagA and vacA were determined by polymerase chain reaction. The genealogy of these Colombian strains was analyzed by MLST. Bacterial population structure was analyzed using STRUCTURE software. RESULTS: H. pylori strains from gastric cancer and duodenal ulcer patients were scattered in the phylogenetic tree; thus, we did not detect any difference in phylogenetic distribution between gastric cancer and duodenal ulcer strains in the hpEurope group in Colombia. Sixty-six strains, with one exception, were classified as hpEurope irrespective of the cagA and vacA genotypes, and type of disease. STRUCTURE analysis revealed that Colombian hpEurope strains have a phylogenetic connection to Spanish strains. CONCLUSIONS: Our study showed that a phylogeographic origin determined by MLST was insufficient for distinguishing between gastric cancer and duodenal ulcer risk among hpEurope strains in the Andean region in Colombia. Our analysis also suggests that hpEurope strains in Colombia were primarily introduced by Spanish immigrants. PMID- 25121771 TI - Brain tumor classification using the diffusion tensor image segmentation (D-SEG) technique. AB - BACKGROUND: There is an increasing demand for noninvasive brain tumor biomarkers to guide surgery and subsequent oncotherapy. We present a novel whole-brain diffusion tensor imaging (DTI) segmentation (D-SEG) to delineate tumor volumes of interest (VOIs) for subsequent classification of tumor type. D-SEG uses isotropic (p) and anisotropic (q) components of the diffusion tensor to segment regions with similar diffusion characteristics. METHODS: DTI scans were acquired from 95 patients with low- and high-grade glioma, metastases, and meningioma and from 29 healthy subjects. D-SEG uses k-means clustering of the 2D (p,q) space to generate segments with different isotropic and anisotropic diffusion characteristics. RESULTS: Our results are visualized using a novel RGB color scheme incorporating p, q and T2-weighted information within each segment. The volumetric contribution of each segment to gray matter, white matter, and cerebrospinal fluid spaces was used to generate healthy tissue D-SEG spectra. Tumor VOIs were extracted using a semiautomated flood-filling technique and D-SEG spectra were computed within the VOI. Classification of tumor type using D-SEG spectra was performed using support vector machines. D-SEG was computationally fast and stable and delineated regions of healthy tissue from tumor and edema. D-SEG spectra were consistent for each tumor type, with constituent diffusion characteristics potentially reflecting regional differences in tissue microstructure. Support vector machines classified tumor type with an overall accuracy of 94.7%, providing better classification than previously reported. CONCLUSIONS: D-SEG presents a user-friendly, semiautomated biomarker that may provide a valuable adjunct in noninvasive brain tumor diagnosis and treatment planning. PMID- 25121772 TI - Hell's BELs: bacterial E3 ligases that exploit the eukaryotic ubiquitin machinery. PMID- 25121770 TI - Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. AB - BACKGROUND: Ependymomas are rare CNS tumors. Previous studies describing the clinical course of ependymoma patients were restricted to small sample sizes, often with patients at a specific institution. METHODS: Clinically annotated ependymoma tissue samples from 19 institutions were centrally reviewed. Patients were all adults aged 18 years or older at the time of diagnosis. Potential prognostic clinical factors identified on univariate analysis were included in a multivariate Cox proportional hazards model with backwards selection to model progression-free survival. RESULTS: The 282 adult ependymoma patients were equally male and female with a mean age of 43 years (range, 18-80y) at diagnosis. The majority were grade II (78%) with the tumor grade for 20 cases being reclassified on central review (half to higher grade). Tumor locations were spine (46%), infratentorial (35%), and supratentorial (19%). Tumor recurrence occurred in 26% (n = 74) of patients with a median time to progression of 14 years. A multivariate Cox proportional hazards model identified supratentorial location (P < .01), grade III (anaplastic; P < .01), and subtotal resection, followed or not by radiation (P < .01), as significantly increasing risk of early progression. CONCLUSIONS: We report findings from an ongoing, multicenter collaboration from a collection of clinically annotated adult ependymoma tumor samples demonstrating distinct predictors of progression-free survival. This unique resource provides the opportunity to better define the clinical course of ependymoma for clinical and translational studies. PMID- 25121773 TI - Effects of aprepitant on the pharmacokinetics of controlled-release oral oxycodone in cancer patients. AB - PURPOSE: Oxycodone is a u-opioid receptor agonist widely used in the treatment of cancer pain. The predominant metabolic pathway of oxycodone is CYP3A4-mediated N demethylation to noroxycodone, while a minor proportion undergoes 3-O demethylation to oxymorphone by CYP2D6. The aim of this study was to investigate the effects of the mild CYP3A4 inhibitor aprepitant on the pharmacokinetics of orally administered controlled-release (CR) oxycodone. METHOD: This study design was an open-label, single-sequence with two phases in cancer patients with pain who continued to be administered orally with multiple doses of CR oxycodone every 8 or 12 hours. Plasma concentration of oxycodone and its metabolites were measured up to 8 hours after administration as follows: on day 1, CR oxycodone was administered alone; on day 2, CR oxycodone was administered with aprepitant (125 mg, at the same time of oxycodone dosing in the morning). The steady-state trough concentrations (Css) were measured from day 1 to day 3. RESULTS: Aprepitant increased the area under the plasma concentration-time curve (AUC0-8) of oxycodone by 25% (p<0.001) and of oxymorphone by 34% (p<0.001), as well as decreased the AUC0-8 of noroxycodone by 14% (p<0.001). Moreover, aprepitant increased Css of oxycodone by 57% (p = 0.001) and of oxymorphone by 36% (p<0.001) and decreased Css of noroxycodone by 24% (p = 0.02) at day 3 compared to day 1. CONCLUSIONS: The clinical use of aprepitant in patients receiving multiple doses of CR oxycodone for cancer pain significantly altered plasma concentration levels, but would not appear to need modification of the CR oxycodone dose. TRIAL REGISTRATION: UMIN.ac.jp UMIN000003580. PMID- 25121774 TI - Impact of propofol anaesthesia on cytokine expression profiles in the developing rat brain: a randomised placebo-controlled experimental in-vivo study. AB - BACKGROUND: Recent experimental data indicate that volatile anaesthetics can induce a neuroinflammatory response in the central nervous system. The questions of to what extent this occurs in the developing brain and whether nonvolatile anaesthetics are also involved remain unanswered. OBJECTIVES: The objective of this study is to investigate the impact of propofol anaesthesia on cytokine mRNA expression profiles in the neonatal brain at defined stages of the brain growth spurt. DESIGN: A randomised placebo-controlled experimental in-vivo study. SETTING: Translational research laboratories at the University of Geneva Medical School. METHODS: Wistar rats received 6-h propofol anaesthesia at postnatal day 10 or 20. A quantitative real-time PCR was used to evaluate the impact of this treatment paradigm on mRNA expression profiles of selected members of the cytokine family in the prefrontal cortex and hippocampus. RESULTS: Propofol anaesthesia induced a transient 1.8-fold (interquartile range, IQR 1.7 to 2.2) increase (P = 0.004) in prefrontal but not hippocampal tumour necrosis factor mRNA concentrations in 10-day-old animals. No such effect was detected in 20-day old animals. No changes in mRNA concentrations of two other pro-inflammatory cytokines, interleukins IL-6 and IL-1beta, were detected following drug exposure at any developmental stages or in any studied brain regions. In contrast, propofol anaesthesia at postnatal day 10 induced a transient increase in the mRNA expression patterns of two chemokines: Ccl2 and Ccl3 [for Ccl2 mRNA: 4.4-fold (3.8 to 5.6) increase in the prefrontal cortex, P = 0.0002 and a 3.5-fold (2.8 to 5.3) increase in the hippocampus, P = 0.0001; for Ccl3 mRNA: 2.9-fold (2.6 to 4.31) increase in the prefrontal cortex, P = 0.0001, and a 2.7-fold (2.2 to 3.6) increase in the hippocampus, P = 0.0003]. Propofol did not affect Ccl2 and Ccl3 mRNA concentrations in 20-day-old animals. In addition, it did not impact on two other members of the chemokine family, Cxcl1 and Cx3cl1, at any time points or in any brain regions investigated. CONCLUSION: This study suggests that propofol anaesthesia does not have a major impact on pro-inflammatory cytokine expression profiles in the developing central nervous system during the brain growth spurt. These results raise arguments against the involvement of neuroinflammatory pathways in propofol-related neurotoxicity observed following the administration of this drug in the early postnatal period. PMID- 25121775 TI - Mortality in patients with AIDS-related cytomegalovirus retinitis in Myanmar. PMID- 25121777 TI - Effect of human immunodeficiency virus infection on plasma bactericidal activity against Salmonella enterica serovar Typhimurium. AB - Individuals with human immunodeficiency virus (HIV) infection have increased susceptibility to invasive disease caused by Salmonella enterica serovar Typhimurium. Studies from Africa have suggested that this susceptibility is related in part to the development of a high level of lipopolysaccharide (LPS) specific IgG that is able to inhibit the killing of S. Typhimurium by bactericidal antibodies in healthy individuals. To explore this issue further, we examined the bactericidal activity against S. Typhimurium using serum and plasma samples from healthy controls and various clinical subgroups of HIV-infected adults in the United States. We found that the bactericidal activity in the samples from HIV-positive elite controllers was comparable to that from healthy individuals, whereas it was significantly reduced in HIV-positive viremic controllers and untreated chronic progressors. As demonstrated previously for healthy controls, the bactericidal activity of the plasma from the elite controllers was inhibited by preincubation with S. Typhimurium LPS, suggesting that it was mediated by anti-LPS antibodies. S. Typhimurium LPS-specific IgG was significantly reduced in all subgroups of HIV-infected individuals. Interestingly, and in contrast to the healthy controls, plasma from all HIV positive subgroups inhibited in vitro killing of S. Typhimurium by plasma from a healthy individual. Our results, together with the findings from Africa, suggest that multiple mechanisms may be involved in the HIV-induced dysregulation of humoral immunity to S. Typhimurium. PMID- 25121778 TI - Decorin binding proteins A and B in the serodiagnosis of Lyme disease in North America. AB - The laboratory diagnosis of Lyme disease is based upon the detection of antibodies generated against Borrelia burgdorferi using a two-tier assay, typically consisting of an enzyme-linked immunosorbent assay (ELISA), followed by a Western blot. This system, put into place to address the nonspecificity associated with standalone first-tier assays, is insensitive for diagnosing early infection, when most people seek care. The use of bacterial lysates or whole protein antigens as first-tier assay targets contributes to nonspecificity due, in part, to the presence of cross-reactive epitopes that are also found in other bacteria. This precludes their use as sensitive standalone assays. The use of peptides containing linear epitopes that are highly specific for B. burgdorferi offers a method for reducing this cross-reactivity. In the present study, we mapped the linear epitopes of the prominently expressed Borrelia adhesins decorin binding protein A (DbpA) and DbpB. We identified several epitopes in each protein that were highly conserved among North American strains of B. burgdorferi, and we screened peptides containing specific epitopes using serum panels from early and late Lyme disease patients. The individual peptides primarily detected IgM but not IgG, while the proteins efficiently detected both IgM and IgG. While no individual peptide demonstrated better utility for antibody detection than its respective whole protein, an assay containing a combination of a DbpA and a DbpB peptide adequately detected both IgM and IgG, accurately identifying 87.5% (84/96) of the early Lyme disease patients and 80.0% (16/20) of the late Lyme disease patients. PMID- 25121776 TI - Analysis of mutant SOD1 electrophoretic mobility by Blue Native gel electrophoresis; evidence for soluble multimeric assemblies. AB - Mutations in superoxide dismutase 1 (SOD1) cause familial forms of amyotrophic lateral sclerosis (fALS). Disease causing mutations have diverse consequences on the activity and half-life of the protein, ranging from complete inactivity and short half-life to full activity and long-half-life. Uniformly, disease causing mutations induce the protein to misfold and aggregate and such aggregation tendencies are readily visualized by over-expression of the proteins in cultured cells. In the present study we have investigated the potential of using immunoblotting of proteins separated by Blue-Native gel electrophoresis (BNGE) as a means to identify soluble multimeric forms of mutant protein. We find that over expressed wild-type human SOD1 (hSOD1) is generally not prone to form soluble high molecular weight entities that can be separated by BNGE. For ALS mutant SOD1, we observe that for all mutants examined (A4V, G37R, G85R, G93A, and L126Z), immunoblots of BN-gels separating protein solubilized by digitonin demonstrated varied amounts of high molecular weight immunoreactive entities. These entities lacked reactivity to ubiquitin and were partially dissociated by reducing agents. With the exception of the G93A mutant, these entities were not reactive to the C4F6 conformational antibody. Collectively, these data demonstrate that BNGE can be used to assess the formation of soluble multimeric assemblies of mutant SOD1. PMID- 25121779 TI - The Staurotypus turtles and aves share the same origin of sex chromosomes but evolved different types of heterogametic sex determination. AB - Reptiles have a wide diversity of sex-determining mechanisms and types of sex chromosomes. Turtles exhibit temperature-dependent sex determination and genotypic sex determination, with male heterogametic (XX/XY) and female heterogametic (ZZ/ZW) sex chromosomes. Identification of sex chromosomes in many turtle species and their comparative genomic analysis are of great significance to understand the evolutionary processes of sex determination and sex chromosome differentiation in Testudines. The Mexican giant musk turtle (Staurotypus triporcatus, Kinosternidae, Testudines) and the giant musk turtle (Staurotypus salvinii) have heteromorphic XY sex chromosomes with a low degree of morphological differentiation; however, their origin and linkage group are still unknown. Cross-species chromosome painting with chromosome-specific DNA from Chinese soft-shelled turtle (Pelodiscus sinensis) revealed that the X and Y chromosomes of S. triporcatus have homology with P. sinensis chromosome 6, which corresponds to the chicken Z chromosome. We cloned cDNA fragments of S. triporcatus homologs of 16 chicken Z-linked genes and mapped them to S. triporcatus and S. salvinii chromosomes using fluorescence in situ hybridization. Sixteen genes were localized to the X and Y long arms in the same order in both species. The orders were also almost the same as those of the ostrich (Struthio camelus) Z chromosome, which retains the primitive state of the avian ancestral Z chromosome. These results strongly suggest that the X and Y chromosomes of Staurotypus turtles are at a very early stage of sex chromosome differentiation, and that these chromosomes and the avian ZW chromosomes share the same origin. Nonetheless, the turtles and birds acquired different systems of heterogametic sex determination during their evolution. PMID- 25121782 TI - Abdominoplasty-derived dermal-fat graft augmentation gluteoplasty. AB - BACKGROUND: Plastic surgeons are exploring novel techniques for augmentation gluteoplasty as the demand for this procedure increases annually in the United States. OBJECTIVES: The authors retrospectively reviewed a series of lower abdominal dermal-fat graft augmentation gluteoplasties to validate the procedure. METHODS: Nine consecutive patients underwent abdominoplasty or torsoplasty in which 2 oval dermal-fat grafts were excised, de-epithelialized, and then implanted into subfascial gluteal pockets for augmentation. All operations were independently conducted by 1 of 2 surgeons at facilities in Maryland and New Jersey. RESULTS: The mean age of the 9 female patients was 46 years. The mean dermal-graft size was 188 cm(2), and the mean graft weight was 288 g. One graft became infected and required excision 39 days after the procedure. There were no other complications. All surviving grafts provided a substantial increase in posterior projection and long-lasting gluteal volume. CONCLUSIONS: Dermal-fat graft augmentation gluteoplasty provides a voluminous, natural-feeling, and durable aesthetic result. The procedure should be considered a viable option for patients undergoing abdominoplasty or torsoplasty, especially as more experience is gained. LEVEL OF EVIDENCE: 4. PMID- 25121780 TI - Structural characterization of the DC-SIGN-Lewis(X) complex. AB - Dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a C-type lectin highly expressed on the surface of antigen presenting dendritic cells. DC-SIGN mediates interactions among dendritic cells, pathogens, and a variety of epithelia, myeloid cells, and endothelia by binding to high mannose residues on pathogenic invaders or fucosylated residues on the membranes of other immune cells. Although these interactions are normally beneficial, they can also contribute to disease. The structural characterization of binding geometries is therefore of interest as a basis for the construction of mimetics that can mediate the effects of abnormal immune response. Here, we report the structural characteristics of the interaction of the DC-SIGN carbohydrate recognition domain (CRD) with a common fucosylated entity, the Lewis(X) trisaccharide (Le(X)), using NMR methods. Titration of the monomeric DC SIGN CRD with Le(X) monitored by 2D NMR revealed significant perturbations of DC SIGN cross-peak positions in (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra and identified residues near the binding site. Additionally, saturation transfer difference (STD) and transferred nuclear Overhauser effect (trNOE) NMR experiments, using a tetrameric form of DC-SIGN, identified binding epitopes and bound conformations of the Le(X) ligand. The restraints derived from these multiple experiments were used to generate models for the binding of Le(X) to the DC-SIGN CRD. Ranking of the models based on the fit of model-based simulations of the trNOE data and STD buildup curves suggested conformations distinct from those seen in previous crystal structures. The new conformations offer insight into how differences between binding of Lewis(X) and mannose terminated saccharides may be propagated. PMID- 25121784 TI - Effectiveness of prophylactic antibiotics in outpatient plastic surgery. AB - BACKGROUND: The effectiveness of prophylactic antibiotics has not been established for patients who undergo plastic surgery as outpatients, and consensus guidelines for antibiotic administration in clean-contaminated plastic surgery are not available. OBJECTIVES: In a retrospective study of outpatients, the authors examined preoperative timing of prophylactic antibiotics, whether postoperative antibiotics were administered, and whether any correlations existed between these practices and surgical complications. METHODS: The medical records of 468 plastic surgery outpatients were reviewed. Collected data included preoperative antibiotic timing, postoperative antibiotic use, comorbidities, and complications. Rates of complications were calculated and compared with other data. RESULTS: All 468 patients received antibiotics preoperatively, but only 93 (19.9%) received them >=1 hour before the initial incision. Antibiotics were administered 15 to 44 minutes before surgery in 217 patients (46.4%). There was no significant difference in complication rates between the 315 patients who received postoperative prophylactic antibiotics (16.2%) and the 153 who did not (20.9%). Comorbidities had no bearing on postoperative complications. CONCLUSIONS: Postoperative antibiotic prophylaxis may be unnecessary for outpatient plastic surgery patients. LEVEL OF EVIDENCE: 3. PMID- 25121786 TI - Anatomy of the sternal origin of the pectoralis major: implications for subpectoral augmentation. AB - BACKGROUND: The pectoralis major typically is manipulated for implant coverage and pocket design in subpectoral breast augmentation. An understanding of its anatomy can guide successful creation of the implant pocket. OBJECTIVES: The authors evaluated the anatomy of the sternal origin of the pectoralis major to inform surgical planning, help establish a technique for subpectoral augmentation mammaplasty, and identify the most common locations of perforators. METHODS: The sternal origins of 24 pectoralis major muscles were dissected and examined in 15 female cadavers to determine the structure and width of the pectoralis major sternal origin and its relationship to the locations of internal mammary perforators. RESULTS: The average width of the sternal origin of the pectoralis major was 7.1 mm (range, 3 mm-1.8 cm). This width decreased slightly from the second rib to the second intercostal space and then increased progressively in the caudal direction toward the fifth rib. The sternal origin terminated an average of 5.4 mm (range, 1-16 mm) from the midline, with the greatest distance at the fifth rib and large variability throughout. A row of perforators from the internal mammary artery traversed the subpectoral space an average of 2.7 cm from the midline (range, 1-3.7 cm). CONCLUSIONS: The sternal origin of the pectoralis major was thin and highly variable, suggesting that its partial release for implant medialization during subpectoral augmentation is unsafe. PMID- 25121785 TI - Will 1-stage implant salvage after periprosthetic breast infection ever be routine? A 6-year successful experience. AB - BACKGROUND: Concomitant with the recent increase in breast augmentations has been an increase in periprosthetic infections necessitating further surgery. The conventional treatment of periprosthetic infections has been a multistage procedure involving explantation, control of infection, and reimplantation. OBJECTIVES: The authors describe a 1-stage salvage procedure for the management of periprosthetic infections. This technique may become the standard for managing infection following cosmetic breast surgery. METHODS: The authors performed a retrospective review of all patients who had periprosthetic infection following cosmetic breast augmentation. The treatment included explantation, sequential cleaning of the wound, and immediate insertion of a new prosthesis and drain. All patients received intravenous antibiotics postoperatively. Of 3012 patients undergoing primary breast augmentation, periprosthetic infection developed in 17 patients. These 17 patients underwent 1-stage implant salvage. Patients were monitored for <=6 years. RESULTS: All implants were retained; aesthetic results were satisfactory; and no significant adverse events were recorded after implant salvage. CONCLUSIONS: One-stage implant salvage for periprosthetic infection has similar outcomes to conventional multistage procedures and may be preferred by patients. LEVEL OF EVIDENCE: 4. PMID- 25121787 TI - The oncoplastic reduction approach to breast conservation therapy: benefits for margin control. AB - BACKGROUND: Reduction mammaplasty during lumpectomy allows more generous resection and minimizes potential for poor cosmesis as compared with breast conservation therapy alone. OBJECTIVES: The authors assessed the benefits of oncoplastic reduction for margin status in patients with breast cancer by conducting a retrospective review of cases of tumor resection alone vs tumor resection with oncoplastic reduction. METHODS: Patients with breast cancer who underwent lumpectomy performed by a single oncologic surgeon between 2009 and 2013 were included. Patients were stratified into 2 groups based on surgical procedure: tumor resection with oncoplastic reduction (group 1) vs tumor resection alone (group 2). Patient demographics including risk factors, diagnosis, cancer stage, and procedure type were recorded. Tumor size, specimen weight, width of narrowest margin, and receptor status were determined. Outcome variables included margin positivity (<=1 mm), need for re-excision, and conversion to completion mastectomy. RESULTS: A total of 222 breasts from 207 patients were included in the study: 83 in group 1 and 139 in group 2. The patients in group 1 had a lower incidence of positive margins and wider free surgical margins, required re-excision less often, and went on to completion mastectomy less often. Patients in group 1 were younger and had cancer that was more advanced. When controlling for these variables on multivariate regression analysis, the oncoplastic technique was independently associated with fewer positive margins and fewer instances of re-excision. CONCLUSIONS: The oncoplastic reduction technique achieves wider free margins and less often necessitates re excision or subsequent mastectomy. The long-term oncologic effect of this approach deserves further study. LEVEL OF EVIDENCE: 4. PMID- 25121788 TI - The pull-up spreader high (PUSH) technique for nasal tip support. AB - BACKGROUND: Nasal tip depression is associated with nasal valve collapse. The pull-up spreader high (PUSH) technique was developed to enlarge the nasal dorsum and upwardly rotate and define the nasal tip by lifting the domes. OBJECTIVES: The authors reviewed a case series to assess the long-term effectiveness of the PUSH technique in improving nasal airflow and aesthetic outcomes. METHODS: This retrospective study included 50 consecutive cases of PUSH rhinoplasty. Objective (acoustic rhinomanometry) and subjective (patient questionnaire) evaluations of the stability of the aesthetic result and improvement of airflow were conducted before and 3 years after PUSH rhinoplasty. RESULTS: PUSH rhinoplasty resulted in long-term stability of the aesthetic effect. All patients had pleasing aesthetic results and a general improvement in the nasal airway. When the degree of nasal obstruction was scored from 1 (greatest obstruction) to 10 (least obstruction), 22 patients rated their nasal function improved to a score of 10 and 28 patients to a score of 8. Rhinomanometry indicated that only 1 patient had worsened nasal airflow. CONCLUSIONS: The PUSH technique enables stable upward rotation and improved definition of the severely depressed nasal tip through an open approach. LEVEL OF EVIDENCE: 4. PMID- 25121789 TI - Task shifting for non-communicable disease management in low and middle income countries--a systematic review. AB - BACKGROUND: One potential solution to limited healthcare access in low and middle income countries (LMIC) is task-shifting- the training of non-physician healthcare workers (NPHWs) to perform tasks traditionally undertaken by physicians. The aim of this paper is to conduct a systematic review of studies involving task-shifting for the management of non-communicable disease (NCD) in LMIC. METHODS: A search strategy with the following terms "task-shifting", "non physician healthcare workers", "community healthcare worker", "hypertension", "diabetes", "cardiovascular disease", "mental health", "depression", "chronic obstructive pulmonary disease", "respiratory disease", "cancer" was conducted using Medline via Pubmed and the Cochrane library. Two reviewers independently reviewed the databases and extracted the data. FINDINGS: Our search generated 7176 articles of which 22 were included in the review. Seven studies were randomised controlled trials and 15 were observational studies. Tasks performed by NPHWs included screening for NCDs and providing primary health care. The majority of studies showed improved health outcomes when compared with usual healthcare, including reductions in blood pressure, increased uptake of medications and lower depression scores. Factors such as training of NPHWs, provision of algorithms and protocols for screening, treatment and drug titration were the main enablers of the task-shifting intervention. The main barriers identified were restrictions on prescribing medications and availability of medicines. Only two studies described cost-effective analyses, both of which demonstrated that task-shifting was cost-effective. CONCLUSIONS: Task-shifting from physicians to NPHWs, if accompanied by health system re-structuring is a potentially effective and affordable strategy for improving access to healthcare for NCDs. Since the majority of study designs reviewed were of inadequate quality, future research methods should include robust evaluations of such strategies. PMID- 25121791 TI - Flow-diverting stents for intracranial bifurcation aneurysm treatment. AB - BACKGROUND: Although initially considered safe when covering bifurcation sites, flow-diverting stents may provoke thrombosis of side branches that are covered during aneurysm treatment. OBJECTIVE: To understand the occurrence and clinical expression of side-branch remodeling in distal intracranial arterial sites after flow diverter deployment by means of correlation of imaging and clinical data. METHODS: We analyzed our prospectively collected data on a series of patients treated with flow diverters for intracranial aneurysms at bifurcation sites. From February 2011 to May 2013, 32 patients with 37 aneurysms (anterior communicating artery, 9 [24.3%]; anterior cerebral artery, 5 [13.5%]; middle cerebral artery, 19 (51.4%); terminal internal carotid artery, 4 [10.8%]) were treated. We divided aneurysms into 2 groups based on the side branches covered by the stent during treatment. Group A consisted of cases with side branches that supplied brain territories also receiving a direct collateral supply. Group B consisted of cases in which side branches supplied territories without direct collateral supply. The 2 groups were compared statistically. RESULTS: Total exclusion occurred in 97.3% of aneurysms at follow-up. Initial modified Rankin Scale (mRS) score was 0 to 1 for 29 patients (90.6%) and 2 for 3 patients (9.4%). New permanent neurological deficit was reported in 3 patients (9.4%). At the 6-month follow-up, the mRS score was 0 to 1 for 31 patients (96.8%) and 3 for 1 patient (3.2%). Although 78.5% of side branches in group A underwent narrowing or occlusion after 6 months, no new stroke was found on magnetic resonance imaging. CONCLUSION: Symptomatic modifications of side branches after flow diverter treatment depend on the extent and type of collateral supply. PMID- 25121792 TI - A novel protocol of continuous navigation guidance for endoscopic third ventriculostomy. AB - BACKGROUND: Although considered a standard neurosurgical procedure, endoscopic third ventriculostomy (ETV) is associated with a relatively high complication rate that is predominantly related to malpositioning of the trajectory. OBJECTIVE: To develop an advanced navigation protocol for ETV, assess its possible benefits over commonly used ETV trajectories, and apply this protocol during surgery. METHODS: After development of our advanced protocol, the imaging data of 59 patients who underwent ETV without navigation guidance was transferred to our navigation software. An individualized endoscope trajectory was created according to our protocol in all cases. This trajectory was compared with 2 standard trajectories, especially with regard to the distance to relevant neuronal structures: a trajectory manually measured on preoperative radiological images, as performed in all 59 cases, and a trajectory resulting from a commonly used fixed coronal burr hole. Subsequently, we applied the protocol in 15 ETVs to assess the feasibility and procedural complications. RESULTS: Our individualized trajectory resulted in a significantly greater distance to the margins of the foramen of Monro, and the burr hole was located more posteriorly from the coronal suture in comparison with the standard trajectories. The advanced ETV technique was feasible in all 15 procedures, and no major complications occurred in any procedure. In 1 patient, a fornix contusion without clinical correlation was observed. CONCLUSION: Our data indicate that the proposed navigation protocol for ETV optimizes the distance of the endoscope to important neuronal structures. Continuous endoscope and puncture device guidance may further add to the safety of this procedure. PMID- 25121793 TI - Early postmarket experience after US Food and Drug Administration approval with the Trevo device for thrombectomy for acute ischemic stroke. AB - BACKGROUND: TREVO 2 showed the Trevo stent retriever to be more successful for revascularization than Merci for acute stroke intervention in patients treated within 8 hours of symptom onset. These results led to US Food and Drug Administration approval of Trevo. OBJECTIVE: To report the first postmarket experience with Trevo since US Food and Drug Administration approval at a single high-volume comprehensive stroke center in the United States. METHODS: A retrospective analysis of prospectively collected data was conducted in patients who underwent intervention for ischemic stroke with the Trevo device. Trevo was used alone or in conjunction with other intra-arterial devices. Two groups of patients were identified: those with symptom onset within (group 1) and those with symptom onset beyond (group 2) 8 hours. Recanalization, outcome, symptomatic intracranial hemorrhage, and in-hospital and 90-day mortality were assessed. RESULTS: Fifty-two patients were identified, 27 in group 1 and 25 in group 2. Thrombolysis in Cerebral Infarction grade 2 to 3 revascularization was achieved in 93% of group 1 and 84% of group 2 patients. In-hospital mortality and symptomatic intracranial hemorrhage rates were 3.8% and 12% for groups 1 and 2, respectively. Ninety-day mortality was 15% and 24% for groups 1 and 2, respectively. In groups 1 and 2, 48% and 42% of patients, respectively, had good outcomes (modified Rankin Scale score, 0-2), and 50% in both groups of patients achieved Thrombolysis in Cerebral Infarction grade 3 revascularization. Group 2 had longer revascularization times and required adjuvant devices more frequently. CONCLUSION: Our postmarket experience shows that in highly selected patients Trevo is safe and effective, even beyond 8 hours, despite longer procedure times and the need for adjuvant devices. PMID- 25121794 TI - Journal club: the impact of body mass index on hospital stay and complications after spinal fusion. PMID- 25121795 TI - Response to journal club: the impact of body mass index on hospital stay and complications after spinal fusion. PMID- 25121790 TI - Role of hemoglobin and iron in hydrocephalus after neonatal intraventricular hemorrhage. AB - BACKGROUND: Neonatal germinal matrix hemorrhage/intraventricular hemorrhage is common and often results in hydrocephalus. The pathogenesis of posthemorrhagic hydrocephalus is not fully understood. OBJECTIVE: To explore the potential role of hemoglobin and iron released after hemorrhage. METHODS: Artificial cerebrospinal fluid (aCSF), hemoglobin, or iron was injected into the right lateral ventricle of postnatal day-7 Sprague Dawley rats. Ventricle size, heme oxygenase-1 (HO-1) expression, and the presence of iron were evaluated 24 and 72 hours after injection. A subset of animals was treated with an iron chelator (deferoxamine) or vehicle for 24 hours after hemoglobin injection, and ventricle size and cell death were evaluated. RESULTS: Intraventricular injection of hemoglobin and iron resulted in ventricular enlargement at 24 hours compared with the injection of aCSF. Protoporphyrin IX, the iron-deficient immediate heme precursor, did not result in ventricular enlargement after injection into the ventricle. HO-1, the enzyme that releases iron from heme, was increased in the hippocampus and cortex of hemoglobin-injected animals at 24 hours compared with aCSF-injected controls. Treatment with an iron chelator, deferoxamine, decreased hemoglobin-induced ventricular enlargement and cell death. CONCLUSION: Intraventricular injection of hemoglobin and iron can induce hydrocephalus. Treatment with an iron chelator reduced hemoglobin-induced ventricular enlargement. This has implications for the pathogenesis and treatment of posthemorrhagic hydrocephalus. ABBREVIATIONS: aCSF, artificial cerebrospinal fluidDAB, 3,3'-diaminobenzidine-4HClGMH-IVH, germinal matrix hemorrhage/intraventricular hemorrhageHO-1, heme oxygenase-1ICH, intracerebral hemorrhagePBS, phosphate-buffered salineSVZ, subventricular zoneTBST, tris buffered saline with Tween 20. PMID- 25121796 TI - Let's study how worker health affects the psychosocial work environment. PMID- 25121799 TI - Disability days, United States, 1971. AB - Data are presented in this report on the total number and annual rates per person for disability days experienced by the civilian, noninstitutionalized population for 1971. Disability days included are restricted-activity days, bed days, work loss days, and school-loss days. A day of restricted activity is defined as a day on which a person reduced his normal activities for the entire day because of illness or injury. Bed days, work-loss days, and school-loss days are included in the total number of restricted-activity days. Demographic characteristics used to described the persons with disability days are age, sex, place of residence, geographic region, famiIy income, usual activity, color, employment status, and for the currently employed population, industry and occupation. Previous reports of data from the Health Interview Survey on disability days are pubIished for July 1961-June 1962, July 1963-June 1964, July 1965-June 1966, and January December 1968 in Vital and Health Statistics, Series 10, Numbers 4, 24, 47, and 67. Data on work-loss days for the currently employed during 1968 are discussed in Series 10, Number 71. Summary data from July 1965-June 1966 and January December 1968 are also shown in this report for comparative purposes. PMID- 25121798 TI - Rethinking unmet need: Determinants of contraceptive use in Santiago, the Dominican Republic. AB - Inadequate access to contraceptives is often considered the primary source of unmet need among women who desire to prevent pregnancy. This study evaluates two potential determinants of contraceptive use among Dominican women: (1) perceived access to family planning and (2) perceived personal reproductive control, a measure based in psychological theories of locus of control. Sexually active women aged 18-45 who did not desire fertility were surveyed to assess influences on contraceptive use. In-depth interviews were conducted among a subset of participants to contextualise survey results. Fewer than half (49%) of the 80 survey respondents had used contraception in the last 3 months. Higher personal reproductive control was significantly related to contraceptive use (aOR 1.18, 95% CI 1.04-1.34), however, higher perceived access to contraceptives was not (aOR 1.09, 95% CI 0.97-1.23). Male partner influence was identified as a barrier to contraceptive use. In this population, high personal reproductive control is a better predictor of contraceptive use than perceived access. PMID- 25121800 TI - [Christoph Scheiner and the physiological optics of the eye]. PMID- 25121801 TI - [Treatment options for nystagmus]. AB - The goal of treatment for nystagmus is to reduce or to abolish the typical symptoms associated with nystagmus. These are (i) reduction of visual acuity (and amblyopia in infantile nystagmus), (ii) abnormal head posture (with possible secondary changes of cervical spine) and (iii) oscillopsia (often connected with vertigo and disorders of gait and orientation). Treatment strategies include pharmacological treatment, surgical therapy and optical devices. Choice of treatment depends on the type of nystagmus and its characteristics. SURGICAL THERAPY: The following surgical procedures were successfully used as treatment of selected symptoms: (i) unilateral recess-resect surgery of the dominant eye in infantile esotropia with latent nystagmus for the relief of abnormal head posture, (ii) Kestenbaum operation of both eyes in infantile nystagmus syndrome with excentric null zone and abnormal head posture, (iii) recess-resect surgery to produce artificial exophoria in infantile nystagmus syndrome. PHARMACOLOGICAL TREATMENT: Depending on the pathophysiology of different types of nystagmus, several drugs were effective in clinical application (off-label use): (i) gabapentin (non-selective GABAergic and anti-glutamatergic effect): up to 2400 mg/d in infantile nystagmus, acquired pendular nystagmus and oculopalatal tremor, (ii) nemantine (anti-glutamatergic effect): dosage up to 40 mg/d in infantile nystagmus, also in acquired pendular nystagmus and oculopalatal tremor, (iii) baclofen (GABA-B-receptor agonist): 3 * 5-10 mg/d in periodic alternating nystagmus and in upbeat nystagmus, (iv) 4-aminopyridine (non-selective blocker of voltage-gated potassium channels): 3 * 5 mg/d or 1-2 * 10 mg Fampridin in downbeat nystagmus and upbeat nystagmus, (v) acetazolamide (carbonic anhydrase inhibitor): in hereditary episodic ataxia type 2. OPTICAL DEVICES: (i) Contact lenses are used in infantile nystagmus in order to overcome negative effects of eye glasses in abnormal head posture, lateral gaze, and higher refractive errors, (ii) spectacle prisms are useful to induce an artificial exophoria (base-out prisms) or to shift an excentric null zone (base in direction of head posture) of infantile nystagmus with abnormal head posture, (iii) low vision aids may be necessary and should be prescribed according to magnification requirements. PMID- 25121803 TI - An approach toward constructing the trioxadispiroketal core in the DEF-ring of (+)-spirastrellolide A. AB - A concise and stereoselective synthesis of the trioxadispiroketal motif that embodies the DEF-ring of the marine macrolide (+)-spirastrellolide A is described. The synthetic approach features a sequence of cyclic acetal tethered ring-closing metathesis and Suarez oxidative cyclization, thereby constituting a viable strategy for constructing the Northern Half. PMID- 25121802 TI - Characteristics of fishing operations, environment and life history contributing to small cetacean bycatch in the northeast Atlantic. AB - Fisheries bycatch is a key threat to cetacean species globally. Managing the impact requires an understanding of the conditions under which animals are caught and the sections of the population affected. We used observer data collected on an albacore tuna gillnet fishery in the northeast Atlantic, to assess operational and environmental factors contributing to bycatch of common and striped dolphins, using generalised linear models and model averaging. Life history demographics of the captured animals were also investigated. In both species, young males dominated the catch. The age ratio of common dolphins was significantly different from that estimated for the population in the region, based on life tables (G = 17.1, d.f. = 2, p = 0.002). Skewed age and sex ratios may reflect varying vulnerability to capture, through differences in behaviour or segregation in populations. Adult females constituted the second largest portion of the bycatch for both species, with potential consequences for population sustainability. Depth was the most important parameter influencing bycatch of both species and reflected what is known about common and striped dolphin habitat use in the region as the probability of catching common dolphins decreased, and striped dolphins increased, with increasing depth. Striped dolphin capture was similarly influenced by the extent to which operations were conducted in daylight, with the probability of capture increasing with increased operations in the pre-sunset and post-sunrise period, potentially driven by increased ability of observers to record animals during daylight operations, or by diurnal movements increasing contact with the fishery. Effort, based on net length and soak time, had little influence on the probability of capturing either species. Our results illustrate the importance of assessing the demographic of the animals captured during observer programmes and, perhaps more importantly, suggest that effort restrictions alone may not be sufficient to eradicate bycatch in areas where driftnets and small cetaceans co-occur. PMID- 25121805 TI - Flowing gas in mass spectrometer: method for characterization and impact on ion processing. AB - Mass spectrometers are complex instrumentation systems where ions are transferred though different pressure regions and mass-analyzed under high vacuum. In this work, we have investigated the impact of the gas flows that exit almost universally in all pressure regions. We developed a method that incorporates the dynamic gas field with the electric field in the simulation of ion trajectories. The scope of the electro-hydrodynamic simulation (EHS) method was demonstrated for characterizing the ion optical systems at atmospheric pressure interfaces. With experimental validation, the trapping of the externally injected ions in a linear ion trap at low pressure was also studied. Further development of the EHS method and the knowledge acquired in this research are expected to be useful in the design of hybrid instruments and the study of ion energetics. PMID- 25121804 TI - A randomized, double-blind, placebo-controlled 12 week trial of acetaminophen extended release for the treatment of signs and symptoms of osteoarthritis. AB - OBJECTIVE: Determine efficacy and safety of acetaminophen extended release (ER) 1300 mg given three times daily compared to placebo for relieving signs and symptoms of hip or knee osteoarthritis. RESEARCH DESIGN AND METHODS: Sixty investigators at 58 private, ambulatory, primary care sites in the US enrolled 542 outpatient adults >=40 years old with moderate to severe idiopathic osteoarthritis pain into a randomized, placebo-controlled, double-blind 12 week clinical trial. Patients were randomly assigned to treatment given three times daily of acetaminophen 1300 mg (n = 267) or placebo (n = 275). RESULTS: The three primary endpoints measured through week 12 favored acetaminophen ER as follows: least squares (LS) mean change from baseline for WOMAC physical function subscale score was significantly greater for acetaminophen ER than for placebo (P = 0.011); LS mean patient's global assessment of response to therapy was significantly greater for acetaminophen ER than for placebo (P = 0.010); and LS mean change from baseline for WOMAC pain subscale score was marginally greater for acetaminophen ER than for placebo (P = 0.054). LS mean change from baseline for secondary endpoints through week 12 also favored acetaminophen ER compared with placebo: significantly for WOMAC stiffness subscale score (P = 0.004), significantly for WOMAC total index score (P = 0.013), and marginally for Nottingham Health Profile energy subscale score (P = 0.057). The percentage of patients with any adverse event was similar for both treatment groups. Hepatic transaminases exceeded 3 * ULN in seven acetaminophen ER patients and one placebo patient. Elevations were attributed to health conditions in three of seven acetaminophen ER patients; elevations in the remaining four patients returned to or toward normal. CONCLUSIONS: Acetaminophen ER 1300 mg, a nonprescription drug, given three times daily, can provide effective relief of signs and symptoms of osteoarthritis of the hip or knee and was well tolerated. ClinicalTrials.gov registration number: NCT00240799. PMID- 25121806 TI - Iran plans to ban vasectomies and female sterilisation to boost population. PMID- 25121807 TI - Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members. AB - Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = >= 0.34, p = <0.0001 for all). Seventy five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region. PMID- 25121808 TI - Transnational, social, and neighborhood ties and smoking among Latino immigrants: does gender matter? AB - OBJECTIVES: We examined whether transnational ties, social ties, and neighborhood ties were independently associated with current smoking status among Latino immigrants. We also tested interactions to determine whether these associations were moderated by gender. METHODS: We conducted a series of weighted logistic regression analyses (i.e., economic remittances, number of return visits, friend support, family support, and neighborhood cohesion) using the Latino immigrant subsample (n = 1629) of the National Latino and Asian American Study in 2002 and 2003. RESULTS: The number of past-year return visits to the country-of-origin was positively associated with current smoker status. Gender moderated the association between economic remittances, friend support, and smoking. Remittance behavior had a protective association with smoking, and this association was particularly pronounced for Latino immigrant women. Friendship support lowered the odds of smoking among men, but not women. CONCLUSIONS: Our results underscore the growing importance of transnational networks for understanding Latino immigrant health and the gendered patterns of the associations between social ties, transnational ties, and health risk behaviors. PMID- 25121809 TI - Science as an early driver of policy: child labor reform in the early Progressive Era, 1870-1900. AB - Scientific evidence is an increasingly important driver of social and environmental policy concerning child health. This trend began earlier than generally recognized. The child labor reform movement of the Gilded Age and early Progressive Era reflected not only moral and economic forces but also the dramatic advances during the later decades of the 19th century in scientific knowledge concerning children's biological and psychological vulnerability to environmental and psychosocial stressors. The growing importance of scientific information in shaping policy concerning children's health between 1870 and 1900 is illustrated by the events leading up to and following the New York State Child Labor Law of 1886. Child labor reform during this period was a critical step in the development of a science-based as well as a value-driven movement to protect children's environmental health and well-being that continues today. PMID- 25121811 TI - Instituting a sugar-sweetened beverage ban: experience from a children's hospital. AB - Sugar-sweetened beverage (SSB) consumption is linked to increased weight and obesity in children and remains the major source of added sugar in the typical US diet across all age groups. In an effort to improve the nutritional offerings for patients and employees within our institution, Nationwide Children's Hospital in Columbus, Ohio, implemented an SSB ban in 2011 in all food establishments within the hospital. In this report, we describe how the ban was implemented. We found that an institutional SSB ban altered beverage sales without revenue loss at nonvending food locations. From a process perspective, we found that successful implementation requires excellent communication and bold leadership at several levels throughout the hospital environment. PMID- 25121810 TI - A framework for evaluating the impact of obesity prevention strategies on socioeconomic inequalities in weight. AB - We developed a theoretical framework to organize obesity prevention interventions by their likely impact on the socioeconomic gradient of weight. The degree to which an intervention involves individual agency versus structural change influences socioeconomic inequalities in weight. Agentic interventions, such as standalone social marketing, increase socioeconomic inequalities. Structural interventions, such as food procurement policies and restrictions on unhealthy foods in schools, show equal or greater benefit for lower socioeconomic groups. Many obesity prevention interventions belong to the agento-structural types of interventions, and account for the environment in which health behaviors occur, but they require a level of individual agency for behavioral change, including workplace design to encourage exercise and fiscal regulation of unhealthy foods or beverages. Obesity prevention interventions differ in their effectiveness across socioeconomic groups. Limiting further increases in socioeconomic inequalities in obesity requires implementation of structural interventions. Further empirical evaluation, especially of agento-structural type interventions, remains crucial. PMID- 25121812 TI - Sexual orientation, adult connectedness, substance use, and mental health outcomes among adolescents: findings from the 2009 New York City Youth Risk Behavior Survey. AB - OBJECTIVES: We examined associations between identifying as lesbian, gay, or bisexual (LGB) and lacking a connection with an adult at school on adolescent substance use and mental health outcomes including suicidality. METHODS: We analyzed data from the 2009 New York City Youth Risk Behavior Survey (n=8910). Outcomes of interest included alcohol use, marijuana use, illicit drug use, depressive symptomatology, suicide ideation, and suicide attempt. RESULTS: The prevalence of each outcome was significantly higher among LGB adolescents than heterosexual adolescents and among those who lacked an adult connection at school than among those who did have such a connection. Even when LGB adolescents had an adult connection at school, their odds of most outcomes were significantly higher than for heterosexual adolescents. Those LGB adolescents who lacked a school adult connection had the poorest outcomes (about 45% reported suicide ideation; 31% suicide attempt). CONCLUSIONS: Adolescents who are LGB, particularly those who lack a connection with school adults, are at high risk for substance use and poorer mental health outcomes. Interventions should focus on boosting social support and improving outcomes for this vulnerable group. PMID- 25121813 TI - Physical dating violence victimization among sexual minority youth. AB - OBJECTIVES: We examined (1) whether sexual minority youths (SMYs) are at increased risk for physical dating violence victimization (PDVV) compared with non-SMYs, (2) whether bisexual youths have greater risk of PDVV than lesbian or gay youths, (3) whether youths who have had sexual contact with both sexes are more susceptible to PDVV than youths with same sex-only sexual contact, and (4) patterns of PDVV among SMYs across demographic groups. METHODS: Using 2 measures of sexual orientation, sexual identity and sexual behavior, and compiling data from 9 urban areas that administered the Youth Risk Behavior Surveys from 2001 to 2011, we conducted logistic regression analyses to calculate odds of PDVV among SMYs across demographic sub-samples. RESULTS: SMYs have significantly increased odds of PDVV compared with non-SMYs. Bisexual youths do not have significantly higher odds of PDVV than gay or lesbian youths, but youths who had sexual contact with both-sexes possess significantly higher odds of PDVV than youths with same sex-only sexual contact. These patterns hold for most gender, grade, and racial/ethnic subgroups. CONCLUSIONS: Overall, SMYs have greater odds of PDVV versus non-SMYs. Among SMYs, youths who had sexual contact with both sexes have greater odds of PDVV than youths with same sex-only sexual contact. Prevention programs that consider sexual orientation, support tolerance, and teach coping and conflict resolution skills could reduce PDVV among SMYs. PMID- 25121814 TI - The Affordable Care Act and emergency care. AB - The Affordable Care Act (ACA) will have far-reaching effects on the way health care is designed and delivered. Several elements of the ACA will directly affect both demand for ED care and expectations for its role in providing coordinated care. Hospitals will need to employ strategies to reduce ED crowding as the ACA expands insurance coverage. Discussions between EDs and primary care physicians about their respective roles providing acute unscheduled care would promote the goals of the ACA. PMID- 25121815 TI - A statewide collaboration to initiate mental health screening and assess services for detained youths in Indiana. AB - OBJECTIVES: We describe a statewide effort to implement detention-based mental health screening and assess follow-up services offered to detained youths in Indiana. METHODS: A total of 25,265 detention stays (15,461 unique youths) occurred between January 1, 2008, and December 31, 2011, across 16 detention centers participating in the Indiana Juvenile Mental Health Screening Project. We collected screening results and reports of detention-based follow-up mental health services and referrals from justice system records. RESULTS: Approximately 21% of youths screened positive for mental health issues requiring follow-up. A positive screen significantly predicted that youths would receive a follow-up mental health service or referral while detained or upon detention center discharge, compared with youths who did not screen positive (61% vs 39%). Logistic regression models indicated that a positive screen was associated with (1) contact with a mental health clinician within 24 hours of detention center intake and (2) a mental health referral upon discharge. White youths were more likely than minorities to receive both follow-up services. CONCLUSIONS: Future statewide efforts to improve the mental health of detained youths should incorporate standards for providing appropriate follow-up services in detention centers. PMID- 25121816 TI - The Montana Radon Study: social marketing via digital signage technology for reaching families in the waiting room. AB - OBJECTIVES: I tested a social marketing intervention delivered in health department waiting rooms via digital signage technology for increasing radon program participation among priority groups. METHODS: I conducted a tri-county, community-based study over a 3-year period (2010-2013) in a high-radon state by using a quasi-experimental design. We collected survey data for eligible participants at the time of radon test kit purchase. RESULTS: Radon program participation increased at the intervention site (t38 = 3.74; P = .001; 95% confidence interval [CI] = 4.8, 16.0) with an increase in renters (chi(2)1,228 = 4.3; P = .039), Special Supplementary Nutrition Program for Women, Infants, and Children families (chi(2)1,166 = 3.13; P = .077) and first-time testers (chi(2)1,228 = 10.93; P = .001). Approximately one third (30.3%; n = 30) attributed participation in the radon program to viewing the intervention message. The intervention crossover was also successful with increased monthly kit sales (t37 = 2.69; P = .01; 95% CI = 1.20, 8.47) and increased households participating (t23 = 4.76; P < .001; 95% CI = 3.10, 7.88). CONCLUSIONS: A social marketing message was an effective population-based intervention for increasing radon program participation. The results prompted policy changes for Montana radon programming and adoption of digital signage technology by 2 health departments. PMID- 25121818 TI - Using vignettes to tap into moral reasoning in public health policy: practical advice and design principles from a study on food advertising to children. AB - In this article, we describe a process for designing and applying vignettes in public health policy research and practice. We developed this methodology for a study on moral reasoning underpinning policy debate on food advertising to children. Using vignettes prompted policy actors who were relatively entrenched in particular ways of speaking professionally about a controversial and ethically challenging issue to converse in a more authentic and reflective way. Vignettes hold benefits and complexities. They can focus attention on moral conflicts, draw out different types of evidence to support moral reasoning, and enable simultaneous consideration of real and ideal worlds. We suggest a process and recommendations on design features for crafting vignettes for public health policy. PMID- 25121817 TI - The relationship between gun ownership and stranger and nonstranger firearm homicide rates in the United States, 1981-2010. AB - OBJECTIVES: We examined the relationship between gun ownership and stranger versus nonstranger homicide rates. METHODS: Using data from the Supplemental Homicide Reports of the Federal Bureau of Investigation's Uniform Crime Reports for all 50 states for 1981 to 2010, we modeled stranger and nonstranger homicide rates as a function of state-level gun ownership, measured by a proxy, controlling for potential confounders. We used a negative binomial regression model with fixed effects for year, accounting for clustering of observations among states by using generalized estimating equations. RESULTS: We found no robust, statistically significant correlation between gun ownership and stranger firearm homicide rates. However, we found a positive and significant association between gun ownership and nonstranger firearm homicide rates. The incidence rate ratio for nonstranger firearm homicide rate associated with gun ownership was 1.014 (95% confidence interval=1.009, 1.019). CONCLUSIONS: Our findings challenge the argument that gun ownership deters violent crime, in particular, homicides. PMID- 25121820 TI - Reducing tobacco use and access through strengthened minimum price laws. AB - Higher prices reduce consumption and initiation of tobacco products. A minimum price law that establishes a high statutory minimum price and prohibits the industry's discounting tactics for tobacco products is a promising pricing strategy as an alternative to excise tax increases. Although some states have adopted minimum price laws on the basis of statutorily defined price "markups" over the invoice price, existing state laws have been largely ineffective at increasing the retail price. We analyzed 3 new variations of minimum price laws that hold great potential for raising tobacco prices and reducing consumption: (1) a flat rate minimum price law similar to a recent enactment in New York City, (2) an enhanced markup law, and (3) a law that incorporates both elements. PMID- 25121819 TI - The implications of fundamental cause theory for priority setting. AB - Application of fundamental cause theory to Powers and Faden's model of social justice highlights the ethical superiority of upstream public health interventions. In this article, I assess the ramifications of fundamental cause theory specifically in context of public health priority setting. Ethically optimal public health policy simultaneously maximizes overall population health and compresses health inequalities. The fundamental cause theory is an important framework in helping to identify which categories of public health interventions are most likely to advance these twin goals. PMID- 25121821 TI - Sexual identity, partner gender, and sexual health among adolescent girls in the United States. AB - OBJECTIVES: We examined associations between adolescent girls' sexual identity and the gender of their sexual partners, on one hand, and their reports of sexual health behaviors and reproductive health outcomes, on the other. METHODS: We analyzed weighted data from pooled Youth Risk Behavior Surveys (2005 and 2007) representative of 13 US jurisdictions, focusing on sexually experienced girls in 8th through 12th grade (weighted n=6879.56). We used logistic regression with hierarchical linear modeling to examine the strength of associations between reports about sexual orientation and sexual and reproductive health. RESULTS: Sexual minority girls consistently reported riskier behaviors than did other girls. Lesbian girls' reports of risky sexual behaviors (e.g., sex under the influence of drugs or alcohol) and negative reproductive health outcomes (e.g., pregnancy) were similar to those of bisexual girls. Partner gender and sexual identity were similarly strong predictors of all of the sexual behaviors and reproductive health outcomes we examined. CONCLUSIONS: Many sexual minority girls, whether categorized according to sexual identity or partner gender, are vulnerable to sexual and reproductive health risks. Attention to these risks is needed to help sexual minority girls receive necessary services. PMID- 25121823 TI - Highly luminescent salts containing well-shielded lanthanide-centered complex anions and bulky imidazolium countercations. AB - Four salts containing imidazolium cations and europium(III)- or terbium(III) centered complex anions have been successfully synthesized from an ethanol/H2O solution. The single-crystal X-ray diffraction analyses reveal that these compounds have a common formula of [R][Ln(DETCAP)4] [R = 1-ethyl-3 methylimidazolium (C2mim), Ln = Eu (1) and Tb (2); R = 1-butyl-3 methylimidazolium (C4mim), Ln = Eu (3) and Tb (4); DETCAP = diethyl-2,2,2 trichloroacetylphosphoramidate], in which the lanthanide centers are chelated by four chelating pseudo-beta-diketonate ligands (DETCAP)(-), forming the respective complex anions. Their thermal behaviors and stabilities were also investigated to study the role of the length of the side chain in the cations. Fluorescence measurements at both room temperature and liquid-nitrogen temperature show that these materials show intense characteristic europium(III) or terbium(III) emissions and have long decay times. Their overall quantum yields were determined to be in the range of 30-49%. PMID- 25121822 TI - Reduction in fatalities, ambulance calls, and hospital admissions for road trauma after implementation of new traffic laws. AB - OBJECTIVES: We evaluated the public health benefits of traffic laws targeting speeding and drunk drivers (British Columbia, Canada, September 2010). METHODS: We studied fatal crashes and ambulance dispatches and hospital admissions for road trauma, using interrupted time series with multiple nonequivalent comparison series. We determined estimates of effect using linear regression models incorporating an autoregressive integrated moving average error term. We used neighboring jurisdictions (Alberta, Saskatchewan, Washington State) as external controls. RESULTS: In the 2 years after implementation of the new laws, significant decreases occurred in fatal crashes (21.0%; 95% confidence interval [CI]=15.3, 26.4) and in hospital admissions (8.0%; 95% CI=0.6, 14.9) and ambulance calls (7.2%; 95% CI=1.1, 13.0) for road trauma. We found a very large reduction in alcohol-related fatal crashes (52.0%; 95% CI=34.5, 69.5), and the benefits of the new laws are likely primarily the result of a reduction in drinking and driving. CONCLUSIONS: These findings suggest that laws calling for immediate sanctions for dangerous drivers can reduce road trauma and should be supported. PMID- 25121824 TI - Evolution at a different pace: distinctive phylogenetic patterns of cone snails from two ancient oceanic archipelagos. AB - Ancient oceanic archipelagos of similar geological age are expected to accrue comparable numbers of endemic lineages with identical life history strategies, especially if the islands exhibit analogous habitats. We tested this hypothesis using marine snails of the genus Conus from the Atlantic archipelagos of Cape Verde and Canary Islands. Together with Azores and Madeira, these archipelagos comprise the Macaronesia biogeographic region and differ remarkably in the diversity of this group. More than 50 endemic Conus species have been described from Cape Verde, whereas prior to this study, only two nonendemic species, including a putative species complex, were thought to occur in the Canary Islands. We combined molecular phylogenetic data and geometric morphometrics with bathymetric and paleoclimatic reconstructions to understand the contrasting diversification patterns found in these regions. Our results suggest that species diversity is even lower than previously thought in the Canary Islands, with the putative species complex corresponding to a single species, Conus guanche. One explanation for the enormous disparity in Conus diversity is that the amount of available habitat may differ, or may have differed in the past due to eustatic (global) sea level changes. Historical bathymetric data, however, indicated that sea level fluctuations since the Miocene have had a similar impact on the available habitat area in both Cape Verde and Canary archipelagos and therefore do not explain this disparity. We suggest that recurrent gene flow between the Canary Islands and West Africa, habitat losses due to intense volcanic activity in combination with unsuccessful colonization of new Conus species from more diverse regions, were all determinant in shaping diversity patterns within the Canarian archipelago. Worldwide Conus species diversity follows the well established pattern of latitudinal increase of species richness from the poles towards the tropics. However, the eastern Atlantic revealed a striking pattern with two main peaks of Conus species richness in the subtropical area and decreasing diversities toward the tropical western African coast. A Random Forests model using 12 oceanographic variables suggested that sea surface temperature is the main determinant of Conus diversity either at continental scales (eastern Atlantic coast) or in a broader context (worldwide). Other factors such as availability of suitable habitat and reduced salinity due to the influx of large rivers in the tropical area also play an important role in shaping Conus diversity patterns in the western coast of Africa. PMID- 25121826 TI - Folate ligand anchored liquid crystal microdroplets emulsion for in vitro detection of KB cancer cells. AB - A KB cancer cell-selective, liquid crystal microdroplets emulsion is prepared using folic acid-conjugated block copolymers (PS-b-PAA-FA) and sodium dodecyl sulfate (SDS) as a mediator to induce configurational transitions in 4-cyano-4' pentylbiphenyl (5CB) liquid crystal microdroplets emulsion. The prepared liquid crystal microdroplets emulsion has shown a configurational transition from radial to bipolar on interacting with KB cancer cells, but no transition from radial to bipolar configuration is observed when liquid crystal microdroplets emulsion was allowed to interact with other normal cells such as fibroblast and osteoblast. The KB cancer cell selectivity of liquid crystal microdroplets emulsion has been considered due to the presence of KB cancer cell folate receptor-specific ligand (FA) at the surface of liquid crystal microdroplets, which allowed liquid crystal microdroplets to interact specifically with KB cancer cells. The ligand-receptor interactions have been considered responsible for triggering the configurational transitions from radial to bipolar in liquid crystal microdroplets emulsion. Thus, folate ligand anchored liquid crystal microdroplets emulsion has shown a potential to be used for in vitro detection of KB cancer cells in the early stage of tumor development. PMID- 25121825 TI - Genetic contribution to postpartum haemorrhage in Swedish population: cohort study of 466,686 births. AB - OBJECTIVE: To investigate the familial clustering of postpartum haemorrhage in the Swedish population, and to quantify the relative contributions of genetic and environmental effects. DESIGN: Register based cohort study. SETTING: Swedish population (multi-generation and medical birth registers). MAIN OUTCOME MEASURE: Postpartum haemorrhage, defined as >1000 mL estimated blood loss. PARTICIPANTS: The first two live births to individuals in Sweden in 1997-2009 contributed to clusters representing intact couples (n = 366,350 births), mothers with separate partners (n = 53,292), fathers with separate partners (n = 47,054), sister pairs (n = 97,228), brother pairs (n = 91,168), and mixed sibling pairs (n = 177,944). METHODS: Familial clustering was quantified through cluster specific tetrachoric correlation coefficients, and the influence of potential sharing of known risk factors was evaluated with alternating logistic regression. Relative contributions of genetic and environmental effects to the variation in liability for postpartum haemorrhage were quantified with generalised linear mixed models. RESULTS: The overall prevalence of postpartum haemorrhage after vaginal deliveries in our sample was 4.6%. Among vaginal deliveries, 18% (95% confidence interval 9% to 26%) of the variation in postpartum haemorrhage liability was attributed to maternal genetic factors, 10% (1% to 19%) to unique maternal environment, and 11% (0% to 26%) to fetal genetic effects. Adjustment for known risk factors only partially explained estimates of familial clustering, suggesting that the observed shared genetic and environmental effects operate in part through pathways independent of known risk factors. There were similar patterns of familial clustering for both of the main subtypes examined (atony and retained placenta), though strongest for haemorrhage after retained placenta. CONCLUSIONS: There is a maternal genetic predisposition to postpartum haemorrhage, but more than half of the total variation in liability is attributable to factors that are not shared in families. PMID- 25121828 TI - A single practice's experience of NHS 111. PMID- 25121829 TI - Role of desorption kinetics in the rhamnolipid-enhanced biodegradation of polycyclic aromatic hydrocarbons. AB - The main aim of this study was to investigate the effect of a rhamnolipid biosurfactant on biodegradation of (14)C-labeled phenanthrene and pyrene under desorption-limiting conditions. The rhamnolipid caused a significant solubilization and enhanced biodegradation of PAHs sorbed to soils. The enhancement was, however, negatively influenced by experimental conditions that caused an enrichment of slow desorption fractions. These conditions included aging, a higher organic matter content in soil, and previous extraction with Tenax to remove the labile-desorbing chemical. The decline in bioavailability caused by aging on sorbed (14)C-pyrene was partially reversed by rhamnolipids, which enhanced mineralization of the aged compound, although not so efficiently like with the unaged chemical. This loss in biosurfactant efficiency in promoting biodegradation can be explained by intra-aggregate diffusion of the pollutant during aging. We suggest that rhamnolipid can enhance biodegradation of soil sorbed PAHs by micellar solubilization, which increase the cell exposure to the chemicals in the aqueous phase, and partitioning into soil organic matter, thus enhancing the kinetics of slow desorption. Our study show that rhamnolipid can constitute a valid alternative to chemical surfactants in promoting the biodegradation of slow desorption PAHs, which constitutes a major bottleneck in bioremediation. PMID- 25121827 TI - Systemic injection of CD34(+)-enriched human cord blood cells modulates poststroke neural and glial response in a sex-dependent manner in CD1 mice. AB - Stroke in the developing brain is an important cause of neurological morbidity. We determined the impact of human cord blood-derived CD34(+)-enriched mononuclear cells (CBSC) intraperitoneally injected 48 h after an ischemic stroke at postnatal day 12 by evaluating poststroke neurogenic niche proliferation, glial response, and recovery in CD1 mice. Percent brain atrophy was quantified from Nissl-stained sections. Density of BrdU, Iba-1, and GFAP staining were quantified in the dentate gyrus and the subventricular zone (SVZ). Immunohistochemistry for human nuclear antibody, human mitochondrial antibody, and human CD34(+) cells was done on injured and uninjured brains from CBSC- and vehicle-treated mice. Developmental neurobehavioral milestones were evaluated pre- and post-treatment. No significant differences in stroke severity were noted between CBSC and vehicle treated injured animals. With a 1*10(5) CBSC dose, there was a significant increase in subgranular zone (SGZ) proliferation in the CBSC-versus vehicle treated stroke-injured male mice. SVZ glial fibrillary acidic protein (GFAP) expression was increased contralaterally in injured females treated with CBSC but suppressed in injured males. Significant negative correlations between severity of the stroke-injury and spleen weights, and between spleen weights and SGZ proliferation, and a positive correlation between GFAP expression and severity of brain injury were noted in the vehicle-treated injured mice but not in the CBSC treated mice. GFAP expression and SVZ proliferation were positively correlated. In conclusion, neurogenic niche proliferation and glial brain responses to CBSC after neonatal stroke may involve interactions with the spleen and are sex dependent. PMID- 25121830 TI - The complete mitochondrial DNA of white shark (Carcharodon carcharias) from Isla Guadalupe, Mexico. AB - The Isla Guadalupe white shark mitochondrial structure is similar to the one previously reported for a white shark individual from Taiwan with a total length of 16,745 and 16,742 bp respectively; the base composition of the genomes was as follow A (30.60%), T (28.67%), C (26.86%) and G (13.87%), contains 13 protein coding genes and 24 tRNA genes and the non-coding control region. The tRNA genes range from 70-72 bp. Gene order is the same as in other vertebrates and teleosts. PMID- 25121831 TI - The comparison of two complete mitochondrial genomes of Pseudobagrus ondon (Siluriformes, Bagridae). AB - The complete mitochondrial genome of Pseudobagrus ondon collected from the Qiantang River in Zhejiang Province was determined in this study with polymerase chain reaction. It contained 22 tRNA genes, 13 protein-coding genes, 2 rRNAs and a control region with the base composition 31.03% A, 27.92% C, 25.78% T and 15.27% G. It shared the arrangement pattern that was identical with most vertebrates. Here we compared the complete mitochondrial genome with another Pseudobagrus ondon species has been sequenced before discovering some differences between the two entities belong to the same species. The complete genome of the one in this study was 16,531 bp in length but the other was 16,534 bp. The variable sites and the genetic distances between them were 105 bp and 0.7%, respectively. There was 79 variable sites occurred in the protein-coding genes except that gene ATP8 and ND3 were the same sequences in the two mitogenomes. Considering that relatively little work has been done on the fishes of Pseudobagrus, we hope this study could make some contribution for the phylogenetic relationships of this group of fishes. PMID- 25121832 TI - DNA-barcoding of perch-like fishes (Actinopterygii: Perciformes) from far-eastern seas of Russia with taxonomic remarks for some groups. AB - The analysis of variation among 203 nucleotide sequences of Co-1 gene (DNA barcode) for 45 species, 31 genera and 7 families of the order Perciformes from the Far Eastern seas of Russia has been performed. As a result, 42 species (93.3%) can be unambiguously identified using molecular DNA-barcode at Co-1, whereas more variable markers are required for other species (6.7%): Stichaeus grigorjewi, S. nozawae, and Lumpenus sagitta. The latter includes as well 2 morphologically distinct (by number of vertebrae) but genetically unresolved species, L. sagitta (Sea of Okhotsk) and L. fabricii (Bering Sea). In addition, within this genus morphologically poorly characterized but genetically well distinguished cryptic species has been detected. Amphi-Pacific distribution is in question relative to L. sagitta. Cryptic diversity was observed in the genus Ammodytes. PMID- 25121833 TI - Evolutionary history and population genetic structure of the endemic tree frog Hyla tsinlingensis (Amphibia: Anura: Hylidae) inferred from mitochondrial gene analysis. AB - The influence of topography and Pleistocenic climatic fluctuations on the population genetic structure of amphibians in the Tsinling-Dabieshan Mountains of China is poorly investigated. Hyla tsinlingensis is a tree frog endemic to the Tsinling-Dabieshan Mountains, with a restricted and patchy distribution that is currently shrinking. We speculated on the evolutionary history of amphibians in this region by studying the population genetic structure of H. tsinlingensis. Using a total of 212 samples, 32 haplotypes and four haplogroups were found in the present study. Population genetic structure showed significant differentiation (F(ST)) between most populations of H. tsinlingensis in the Tsinling-Dabieshan Mountains. An analysis of molecular variance (AMOVA) suggested that most of the observed genetic variation occurs between the two regions (the Tsinling and Dabieshan Mountains). Mantel tests indicated that the genetic divergence was induced through isolation by distance. Using Monmonier's maximum difference algorithm to predict the genetic barrier, two putative barriers in gene flow that separate lineages of H. tsinlingensis were identified. Mismatch distribution and neutrality tests found a sudden population expansion in all haplogroups except the Tsinling population and total population. This population expansion was identified between 0.5 Myr to 0.1 Myr (Quaternary) by Bayesian skyline plot (BSP). Divergence dating indicated the divergence time between the Tsinling population and Dabieshan population to be 3.26 MYA (Pliocene). In conclusion, the topography of the Tsinling and Dabieshan Mountains exerts a significant impact on the population genetic structure of H. tsinlingensis, and climatic oscillations during glacial periods in the Quaternary affected the distribution of H. tsinlingensis. PMID- 25121834 TI - Complete mitochondrial genome of the Antarctic bullhead notothen, Notothenia coriiceps (Perciformes, Nototheniidae). AB - The complete sequence of the mitochondrial genome of Notothenia coriiceps was obtained by genome assembly. The complete sequence was determined to be 18,347 base pairs in length and to contain 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 2 control regions. Of the thirteen protein-coding genes, two genes (cox1 and atp6) had GTG start codons, and six genes (nad2, cox2, cox3, nad3, nad4, and cytb) had incomplete stop codons that require the post transcriptional addition of A bases. The base composition of the mitogenome was 26.3% A, 27.6% T, 17.5% G, and 28.5% C. PMID- 25121835 TI - The complete mitochondrial DNA of the bay snook, Petenia splendida, a native Mexican cichlid. AB - The mitogenome of the tenguayaca, Petenia splendida (GenBank accession number KJ914664) has a total length of 16,518 bp, and the arrangement consist of 15 protein-coding genes, 2 ribosomal RNA (rRNA) genes and 22 transfer RNA (tRNA) genes. Gene order was equal to the mitogenomes of other new world cichlids. PMID- 25121836 TI - Optical temperature sensing based on the near-infrared emissions from Nd3+/Yb3+ codoped CaWO4. AB - Under a 980 nm diode laser excitation, the near-infrared (NIR) emissions from Nd3+:4F7/2, 4F5/2, and 4F3/2 states in Nd3+/Yb3+ codoped CaWO4 powder were studied at temperatures ranging from 303 to 873 K. As the temperature increased, the NIR luminescence intensity was significantly enhanced and nearly 190-fold enhancement was achieved at 873 K compared with that at 303 K. By using the fluorescence intensity ratio technique, the thermometry behaviors through the NIR emissions were investigated. The results illustrate that the sensitivity and the accuracy achieved here are much higher than temperature sensors based on other rare earth ion doped materials. PMID- 25121837 TI - Numerical analysis of efficient light extraction with an elliptical solid immersion lens. AB - We introduce and analyze a design concept based on nonspherical solid immersion lens (SIL) geometry. We find via finite difference time domain (FDTD) simulations that elliptical solid immersion lenses (eSILs) exhibit a notably improved emission directionality compared to the standard SIL design. Large light collection efficiencies are achieved even for small numerical apertures (NAs). For example, using a NA as low as 0.3, over 65% of the total light emitted by a dipole can be collected. PMID- 25121839 TI - Designing metal hemispheres on silicon ultrathin film solar cells for plasmonic light trapping. AB - We systematically investigate the design of two-dimensional silver (Ag) hemisphere arrays on crystalline silicon (c-Si) ultrathin film solar cells for plasmonic light trapping. The absorption in ultrathin films is governed by the excitation of Fabry-Perot TEMm modes. We demonstrate that metal hemispheres can enhance absorption in the films by (1) coupling light to c-Si film waveguide modes and (2) exciting localized surface plasmon resonances (LSPRs). We show that hemisphere arrays allow light to couple to fundamental TEm and TMm waveguide modes in c-Si film as well as higher-order versions of these modes. The near field light concentration of LSPRs also may increase absorption in the c-Si film, though these resonances are associated with significant parasitic absorption in the metal. We illustrate how Ag plasmonic hemispheres may be utilized for light trapping with 22% enhancement in short-circuit current density compared with that of a bare 100 nm thick c-Si ultrathin film solar cell. PMID- 25121838 TI - Continuously tuning effective refractive index based on thermally controllable magnetic metamaterials. AB - By employing a thermally active magnetic material, we theoretically design a kind of electromagnetic metamaterial with intrinsic magnetic response, termed magnetic metamaterial (MM). The retrieved effective electric permittivity epsilon(eff) and magnetic permeability MU(eff) exhibit a nearly continuous transition from double negative to double zero, and then to double positive by controlling the temperature, indicating a flexible tunability of the effective refractive index. The beam splitting, collimation, focusing, and total reflection are achieved at different typical temperatures. Most importantly, with the MM implemented under a gradient temperature, a gradient negative-zero-positive index metamaterial (NZPIM) can possibly be realized, thus providing a new platform to study wave features in NZPIM. PMID- 25121840 TI - Low-threshold Brillouin laser at 2 MUm based on suspended-core chalcogenide fiber. AB - We present, to the best of our knowledge, the first demonstration of a 2 MUm Brillouin laser based on a thulium-doped fiber pump and a chalcogenide fiber. A short 1.5 m piece of suspended-core chalcogenide As38Se62 fiber is employed as a gain medium, taking advantage of its small effective mode area and high Brillouin gain coefficient. A record-low lasing threshold of 52 mW is achieved, which is about 10 times lower than previously demonstrated in silica fiber cavities. PMID- 25121841 TI - Prospects for diode-pumped alkali-atom-based hollow-core photonic-crystal fiber lasers. AB - By employing large hollow-core Kagome fiber in a double-clad configuration, the performance of a potentially rubidium vapor-based fiber laser is explored. The absorbed power and laser efficiency versus pump power are calculated utilizing a simple laser model. Our results show that a Kagome-based high-power fiber laser is feasible provided that the value of the collisional fine-structure mixing rate will be elevated by increasing the ambient temperature or by increasing the helium pressure. PMID- 25121842 TI - Post-filament self-trapping of ultrashort laser pulses. AB - Laser filamentation is understood to be self-channeling of intense ultrashort laser pulses achieved when the self-focusing because of the Kerr nonlinearity is balanced by ionization-induced defocusing. Here, we show that, right behind the ionized region of a laser filament, ultrashort laser pulses can couple into a much longer light channel, where a stable self-guiding spatial mode is sustained by the saturable self-focusing nonlinearity. In the limiting regime of negligibly low ionization, this post-filamentation beam dynamics converges to a large-scale beam self-trapping scenario known since the pioneering work on saturable self focusing nonlinearities. PMID- 25121843 TI - Plasmonic waveguides cladded by hyperbolic metamaterials. AB - Strongly anisotropic media with hyperbolic dispersion can be used for claddings of plasmonic waveguides (PWs). In order to analyze the fundamental properties of such waveguides, we analytically study 1D waveguides arranged from a hyperbolic metamaterial (HMM) in a HMM-Insulator-HMM (HIH) structure. We show that HMM claddings give flexibility in designing the properties of HIH waveguides. Our comparative study on 1D PWs reveals that HIH-type waveguides can have a higher performance than MIM or IMI waveguides. PMID- 25121844 TI - Improved configuration and reduction of phase noise in a narrow linewidth ultrawideband optical RF source. AB - In this Letter, we report on the improved configuration of a widely tunable optical RF generation system, particularly for the generation of low-frequency RF, as well as the reduction of phase noise in that same system. Using an amplitude modulator, a simplified system design was demonstrated with fewer components and improved phase noise performance, especially at RF frequencies below ~36 GHz. Excess phase noise due to acoustic vibrations of the optical fibers was also successfully eliminated by mechanical isolation. A minimum phase noise of -124 dBc/Hz at 10 kHz offset was demonstrated at 4 GHz. PMID- 25121846 TI - Nonlinear switching in a two-concentric-core chalcogenide glass optical fiber for passively mode-locking a fiber laser. AB - We propose an all-fiber mode-locking device, which operates based on nonlinear switching in a novel two-concentric-core fiber structure. The design is particularly attractive given the ease of fabrication and coupling to other components in a mode-locked fiber laser cavity. The nonlinear switching in this coupler is studied, and the relative power transmission is obtained. The analysis shows that this nonlinear switch is practical for mode-locking fiber lasers and is forgiving to fabrication errors. PMID- 25121845 TI - 152 W average power Tm-doped fiber CPA system. AB - A high-power thulium (Tm)-doped fiber chirped-pulse amplification system emitting a record compressed average output power of 152 W and 4 MW peak power is demonstrated. This result is enabled by utilizing Tm-doped photonic crystal fibers with mode-field diameters of 35 MUm, which mitigate detrimental nonlinearities, exhibit slope efficiencies of more than 50%, and allow for reaching a pump-power-limited average output power of 241 W. The high-compression efficiency has been achieved by using multilayer dielectric gratings with diffraction efficiencies higher than 98%. PMID- 25121847 TI - Photo-aligned ferroelectric liquid crystals in microchannels. AB - In this Letter we disclose a method to realize a good alignment of ferroelectric liquid crystals (FLCs) in microchannels, based on photo-alignment. The sulfonic azo dye used in our research offers variable anchoring energy depending on the irradiation energy and thus provides good control on the FLC alignment in microchannels. The good FLC alignment has been observed only when anchoring energy normalized to the capillary diameter is less than the elastic energy of the FLC helix. The same approach can also be used for the different microstructures viz. photonic crystal fibers, microwaveguides, etc. which gives an opportunity for designing a photonic devices based on FLC. PMID- 25121848 TI - Achromatic wide-view circular polarizers for a high-transmittance vertically aligned liquid crystal cell. AB - We propose an optical compensation scheme through which we can eliminate the off axis light leakage in a vertically-aligned liquid crystal cell with circular polarizers. In this scheme, four uniaxial films with complementary dispersion characteristics are used to compensate one another, resulting in achromatic effective phase retardation for off-axis angles. By using the proposed optical compensation, a contrast ratio higher than 2000:1 can be realized over the entire 55 degrees viewing cone in a multi-domain vertical-alignment liquid crystal cell with circular polarizers. PMID- 25121849 TI - Dual spectral-band interferometry for spatio-temporal characterization of high power femtosecond lasers. AB - We present and demonstrate a technique called RED-SEA TADPOLE for the spatio temporal characterization of high peak power femtosecond lasers. It retains the basic principle of an existing method, where a scanning monomode fiber is utilized in an interferometric scheme to measure the spectral amplitude and phase at all points across an ultrashort laser beam. We combine this approach with dual spectral-band interferometry, to correct for all phase errors occurring in this interferometer, thus allowing for the simultaneous measurement of the beam wavefront and pulse front in a collimated beam of large diameter. The generic phase correction procedure implemented here can also be extended to other fiber optic device applications sensitive to phase fluctuations. PMID- 25121850 TI - Size-controlled Ge nanostructures for enhanced Er3+ light emission. AB - The potential of Ge nanoparticles (NPs) embedded in Al2O3 with tunable effective optical bandgap values in the range of 1.0-3.3 eV to induce enhanced Er3+ light emission is investigated. We demonstrate nonresonant indirect excitation of the Er3+ ions mediated by the Ge NPs at room temperature. Efficient Er3+ light emission enhancement is obtained for Ge NPs with large effective optical bandgaps in the range of 1.85 to 2.8 eV. The coupled Ge NP-Er emission shows a negligible thermal quenching from 10 K to room temperature that is related to Er3+ de excitation through thermally activated defect states. PMID- 25121851 TI - Optical feedback frequency stabilized cavity ring-down spectroscopy. AB - We introduce optical feedback frequency stabilized cavity ring-down spectroscopy (OFFS-CRDS), a near-shot-noise-limited technique that combines kilohertz resolution with an absorption detection sensitivity of 5*10(-13) cm(-1) Hz(-1/2). Its distributed feedback laser source is stabilized to a highly stable V-shaped reference cavity by optical feedback and fine-tuned by means of single-sideband modulation. The stability of this narrow laser is transferred to a ring-down (RD) cavity using a new fibered Pound-Drever-Hall (PDH) locking scheme without a dedicated electro-optic phase modulator, yielding several hundred RD events per second. We demonstrate continuous coverage of more than 7 nm with a baseline noise of 5*10(-12) cm(-1) and a dynamic range spanning six decades. With its resonant intracavity light intensity on the order of 1 kW/cm2, the spectrometer was used for observing a Lamb dip in a transition of carbon dioxide involving four vibrational quanta. Saturating such a weak transition at 160 MUW input power, OFFS-CRDS paves the way to Doppler-free molecular overtone spectroscopy for precision measurements of hyperfine structures and pressure shifts. PMID- 25121852 TI - Optical forces and torques on realistic plasmonic nanostructures: a surface integral approach. AB - We develop a novel formalism to calculate the optical forces and torques on complex and realistic nanostructures by combining the surface integral equation (SIE) technique with Maxwell's stress tensor. The optical force is calculated directly on the scatterer surface from the currents obtained from the SIE, which does not require an additional surface to evaluate Maxwell's stress tensor; this is especially useful for intricate geometries such as plasmonic antennas. SIE enables direct evaluation of forces from the surface currents very efficiently and accurately for complex systems. As a proof of concept, we establish the accuracy of the model by comparing the results with the calculations from the Mie theory. The flexibility of the method is demonstrated by simulating a realistic plasmonic system with intricate geometry. PMID- 25121853 TI - Ultracompact silicon-on-insulator polarization rotator for polarization diversified circuits. AB - We present an ultracompact (15.3 MUm long) and high-efficiency silicon-on insulator polarization rotator designed for polarization-diversified circuits. The rotator is comprised of a bilevel-tapered TM0-to-TE1 mode converter and a novel bent-tapered TE1-to-TE0 mode converter. The rotator has a simulated polarization conversion loss lower than 0.2 dB and a polarization-extinction ratio larger than 25 dB over a wavelength range of 80 nm around 1550 nm. The rotator has a SiO2 top-cladding and can be fabricated in a CMOS-compatible process. PMID- 25121854 TI - Local spectroscopy of silver nanowire in different environments excited with a halogen lamp. AB - We report a propagation spectrum detection system in which one end of a plasmonic silver nanowire is locally illuminated from a normal halogen lamp and the scattered light is recorded spectroscopically at the other end. The system is applied to investigate surface plasmon polariton-Fabry-Perot (SPP-FP) modes of silver nanowires with different lengths at air-glass and oil-glass interfaces. The generalized FP model is used to analyze the spectrum, which fits well with the experimental results. The influence of nanowire length and environment on the properties of the FP resonances is discussed. The propagation spectrum detection system will find applications for integrated optical circuits and plasmonic sensing. PMID- 25121855 TI - GeSn/Ge multiquantum well photodetectors on Si substrates. AB - Vertical incidence GeSn/Ge multiquantum well (MQW) pin photodetectors on Si substrates were fabricated with a Sn concentration of 7%. The epitaxial structure was grown with a special low temperature molecular beam epitaxy process. The Ge barrier in the GeSn/Ge MQW was kept constant at 10 nm. The well width was varied between 6 and 12 nm. The GeSn/Ge MQW structures were grown pseudomorphically with the in-plane lattice constant of the Ge virtual substrate. The absorption edge shifts to longer wavelengths with thicker QWs in agreement with expectations from smaller quantization energies for the thicker QWs. PMID- 25121856 TI - Generation of multiple sheets of light using spatial-filtering technique. AB - We develop an optical system for generating multiple light sheets. This is enabled by employing a special class of spatial filters in a cylindrical lens geometry. The proposed binary filter placed at the back aperture of the cylindrical lens results in the generation of a periodic transverse pattern extending along the z axis (i.e., multiple light sheets). Experimental results confirm the generation of multiple light sheets of thickness 6.6 MUm with an intersheet spacing of 13.4 MUm. The proposed imaging technique may facilitate three-dimensional imaging in nano-optics, fluorescence microscopy, and nanobiology. PMID- 25121857 TI - Refocusing criterion via sparsity measurements in digital holography. AB - Several automatic approaches have been proposed in the past to compute the refocus distance in digital holography (DH). However most of them are based on a maximization or minimization of a suitable amplitude image contrast measure, regarded as a function of the reconstruction distance parameter. Here we show that, by using the sparsity measure coefficient regarded as a refocusing criterion in the holographic reconstruction, it is possible to recover the focus plane and, at the same time, establish the degree of sparsity of digital holograms, when samples of the diffraction Fresnel propagation integral are used as a sparse signal representation. We employ a sparsity measurement coefficient known as Gini's index thus showing for the first time, to the best of our knowledge, its application in DH, as an effective refocusing criterion. Demonstration is provided for different holographic configurations (i.e., lens and lensless apparatus) and for completely different objects (i.e., a thin pure phase microscopic object as an in vitro cell, and macroscopic puppets) preparation. PMID- 25121858 TI - Transmission enhancement through square coaxial aperture arrays in metallic film: when leaky modes filter infrared light for multispectral imaging. AB - The diffractive behavior of arrays of square coaxial apertures in a gold layer is studied. These structures exhibit a resonant transmission enhancement that is used to design tunable bandpass filters for multispectral imaging in the 7-13 MUm wavelength range. A modal analysis is used for this design and the study of their spectral features. Thus we show that the resonance peak is due to the excitation of leaky modes of the open photonic structure. Fourier transform infrared (FTIR) spectrophotometry transmission measurements of samples deposited on Si substrate show good agreement with numerical results and demonstrate angular tolerance of up to 30 degrees of the fabricated filters. PMID- 25121859 TI - Quantitative optical inspection of contact lenses immersed in wet cell using swept source OCT. AB - We demonstrate swept source optical coherence tomography (OCT) imaging of contact lenses (CLs) in a wet cell and comprehensive quantitative characterization of CLs from volumetric OCT datasets. The approach is based on a technique developed for lens autopositioning and autoleveling enabled by lateral capillary interactions between the wet cell wall and the lens floating on the liquid surface. The demonstrated OCT imaging has enhanced contrast due to the application of a scattering medium and it improves visualization of both CL interfaces and edges. We also present precise and accurate three-dimensional metrology of soft and rigid CLs based on the OCT data. The accuracy and precision of the extracted lens parameters are compared with the manufacturer's specifications. The presented methodology facilitates industrial inspection methods of the CLs. PMID- 25121861 TI - 100 kHz, 100 ms, 400 J burst-mode laser with dual-wavelength diode-pumped amplifiers. AB - The burst duration of an all-diode-pumped burst-mode laser is extended to 100 ms and 100 kHz (10,000 pulses) by utilizing dual-wavelength diode pumping. Total energies of 225 J at 10 kHz and 400 J at 100 kHz are achieved during the 100 ms burst period at 1064 nm. This represents an order-of-magnitude increase in the number of pulses compared with prior work, while maintaining similar or higher pulse energies. Amplitude tailoring of each pulse is used to flatten the burst profile, reducing the standard deviation in pulse energy over the 100 ms burst from 3.7% to 2.1% with a burst-to-burst standard deviation of 0.8%. PMID- 25121862 TI - Chaotic behavior of cavity solitons induced by time delay feedback. AB - We investigate spatiotemporal dynamics of cavity solitons in a broad area vertical-cavity surface-emitting laser with saturable absorption subject to time delayed optical feedback. We show that the inclusion of feedback leads to a period doubling route to chaos of spatially localized light structures. PMID- 25121860 TI - Handheld photoacoustic microscopy to detect melanoma depth in vivo. AB - We developed handheld photoacoustic microscopy (PAM) to detect melanoma and determine tumor depth in nude mice in vivo. Compared to our previous PAM system for melanoma imaging, a new light delivery mechanism is introduced to improve light penetration. We show that melanomas with 4.1 and 3.7 mm thicknesses can be successfully detected in phantom and in in vivo experiments, respectively. With its deep melanoma imaging ability and handheld design, this system can be tested for clinical melanoma diagnosis, prognosis, and surgical planning for patients at the bedside. PMID- 25121863 TI - Optically pumped distributed feedback dye lasing with slide-coated TiO2 inverse opal slab as Bragg reflector. AB - We demonstrate an optical amplification of organic dye within a TiO2 inverse-opal (IO) distributed feedback (DFB) reflector prepared by a slide-coating method. Highly reflective TiO2 IO film was fabricated by slide coating the binary aqueous dispersions of polystyrene microspheres and charge-stabilized TiO2 nanoparticles on a glass slide and subsequently removing the polymer-opal template. TiO2 IO film was infiltrated, in turn, with the solutions of DCM, a fluorescent dye in various solvents with different indices of refraction. Optical pumping by frequency-doubled Nd:YAG laser resulted in amplified spontaneous emission in each dye solution. In accordance with the semi-empirical simulation by the FDTD method, DCM in ethanol showed the best emission/stopband matching for the TiO2 IO film used in this study. Therefore, photo excitation of a DCM/ethanol cavity showed a single-mode DFB lasing at 640 nm wavelength at moderate pump energy. PMID- 25121864 TI - Electron beam position monitor for a dielectric microaccelerator. AB - We report the fabrication and first demonstration of an electron beam position monitor for a dielectric microaccelerator. This device is fabricated on a fused silica substrate using standard optical lithography techniques and uses the radiated optical wavelength to measure the electron beam position with a resolution of 10 MUm, or 7% of the electron beam spot size. This device also measures the electron beam spot size in one dimension. PMID- 25121865 TI - Effect and elimination of alignment error in an optical fiber current sensor. AB - This Letter demonstrates the effect and elimination of alignment error in an optical fiber current sensor. An optical model is built to illustrate the effect of alignment error, which does not induce zero drift and has a large effect on output accuracy. The total alignment error and modulation angle of the polarization controller are defined as k and theta, respectively. Parameter t is equal to 2theta-2k. An elimination method of the error k is proposed, which corrects the angle theta to keep parameter t at 90 deg. This method avoids the measurement of all splice angles separately. Its feasibility is shown by simulation results. In addition, the measurement method and conditions of parameter t are presented. The final t is about 90.24 deg. Furthermore, the effectiveness of the proposed elimination method is proven by a performance test. PMID- 25121866 TI - Efficient Q-switched Ho:GdVO4 laser resonantly pumped at 1942 nm. AB - An efficient 2 MUm room-temperature Q-switched Ho:GdVO4 laser end-pumped by a 1942 nm Tm-fiber laser is demonstrated. To our knowledge, this is the first report of Q-switched performance of Ho:GdVO4 crystal. A maximum CW output power of 6.85 W under the absorbed pump power of 24.1 W was obtained with a slope efficiency of 39.5% at a temperature of 17 degrees C. With the same absorbed pump power, a maximum output energy per pulse of about 0.9 mJ and minimum pulse width of 4.7 ns were obtained at the pulsed repetition frequency (PRF) of 5 kHz, corresponding to a peak power of approximately 187.2 kW. PMID- 25121867 TI - Photonic generation of triangular pulses based on nonlinear polarization rotation in a highly nonlinear fiber. AB - We propose a novel method to generate triangular pulses based on the nonlinear polarization rotation (NPR) effect in a highly nonlinear fiber. A continuous wave probe beam is polarization-rotated by an intensity-modulated control beam via the NPR effect. A polarization-division-multiplexing emulator is exploited to split the probe beam into two orthogonally polarized states with imbalanced time delay. After detection by a photodetector, a 90 degrees microwave phase shifter is used to compensate the phases of the fundamental and the third-order harmonic components in order to generate triangular pulses. Triangular pulses at 5 and 6 GHz with full duty cycles are experimentally generated. The root mean square errors between the generated and the simulated waveforms are 3.6e-4 and 1e-4 for triangular pulses at 5 and 6 GHz, respectively. PMID- 25121868 TI - Controllable continuous-wave Nd:YVO4 self-Raman lasers using intracavity adaptive optics. AB - A controllable self-Raman laser using an adaptive optics (AO)-based control loop featuring an intracavity deformable mirror is reported. This method has the potential to alleviate thermal lensing within the Raman and laser gain media, and enable solid-state Raman lasers to reach new power levels. A proof-of-concept experiment using a Nd:YVO4 self-Raman laser and resulting in 18% enhancement of the first Stokes output power is reported. Moreover, wavelength selection between two Raman laser outputs (lambda=1109 and 1176 nm) emanating from the 379 and 893 cm(-1) Raman shifts of YVO4, respectively, was achieved using this AO technique. PMID- 25121869 TI - Compact 4.7 W, 18.3% wall-plug efficiency green laser based on an electrically pumped VECSEL using intracavity frequency doubling. AB - We have demonstrated a compact, 4.7 W green laser based on an electrically pumped vertical external-cavity surface emitting laser through intracavity frequency doubling. The overall wall-plug efficiency (electrical to green) was 18.3%. The power fluctuations were measured to be +/-1.4% over a 2 h time period. PMID- 25121870 TI - Fiber-optic ferrule-top nanomechanical resonator with multilayer graphene film. AB - Compact ferrule-top nanomechanical resonators with multilayer graphene (MLG) diaphragms as vibrating elements are demonstrated. The resonators comprise a suspended MLG film supported by a ceramic ferrule with a bore diameter of ~125 MUm. The mechanical resonance of the graphene film is excited and detected by an all-fiber optical interrogation system. Based on a beam-shape graphene mechanical resonator, a force sensitivity of ~3.8 fN/Hz1/2 was theoretically predicted. The integration of nanomechanical graphene film with optical fiber simplifies the excitation and interrogation of the resonator and would allow the development of practical fiber-optic sensors for force, mass, and pressure measurements. PMID- 25121871 TI - Binocular open-view instrument to measure aberrations and pupillary dynamics. AB - We have designed and built a binocular Hartmann-Shack wave-front sensor using a single microlens array and camera for real-time aberration measurement of both eyes in an open-view configuration. Furthermore, the use of a long wavelength (1050 nm) laser diode makes the illumination source completely invisible, so that measurements can be unobtrusively performed while the subject stares at the visual world under realistic conditions. The setup provides a large dynamic range and simultaneous measurements of convergence, pupil size, accommodation, and aberrations. The open-view design not only offers the possibility of measuring the subject's ocular optics under natural conditions but also allows coupling the device with other existing vision testing instruments and setups, which increases its potential to become a powerful tool for different visual optics studies. PMID- 25121872 TI - Speckle phase noise in coherent laser ranging: fundamental precision limitations. AB - Frequency-modulated continuous-wave laser detection and ranging (FMCW LADAR) measures the range to a surface through coherent detection of the backscattered light from a frequency-swept laser source. The ultimate limit to the range precision of FMCW LADAR, or any coherent LADAR, to a diffusely scattering surface will be determined by the unavoidable speckle phase noise. Here, we demonstrate the two main manifestations of this limit. First, frequency-dependent speckle phase noise leads to a non-Gaussian range distribution having outliers that approach the system range resolution, regardless of the signal-to-noise ratio. These outliers are reduced only through improved range resolution (i.e., higher optical bandwidths). Second, if the range is measured during a continuous lateral scan across a surface, the spatial pattern of speckle phase is converted to frequency noise, which leads to additional excess range uncertainty. We explore these two effects and show that laboratory results agree with analytical expressions and numerical simulations. We also show that at 1 THz optical bandwidth, range precisions below 10 MUm are achievable regardless of these effects. PMID- 25121873 TI - Top-hat beam output with 100 MUJ temporally shaped narrow-bandwidth nanosecond pulses from a linearly polarized all-fiber system. AB - We report on an all-fiber system delivering more than 100 MUJ pulses with a top hat beam output in the few nanoseconds regime at 10 kHz. The linearly polarized flattened beam is obtained thanks to a 3-mm-long single-mode microstructured fiber spliced to the amplifier's output. PMID- 25121874 TI - Heterogeneously integrated III-V-on-silicon multibandgap superluminescent light emitting diode with 290 nm optical bandwidth. AB - A broadband superluminescent III-V-on-silicon light-emitting diode (LED) was realized. To achieve the large bandwidth, quantum well intermixing and multiple die bonding of InP on a silicon photonic waveguide circuit were combined for the first time, to the best of our knowledge. The device consists of four sections with different bandgaps, centered around 1300, 1380, 1460, and 1540 nm. The fabricated LEDs were connected on-chip in a serial way, where the light generated in the smaller bandgap sections travels through the larger bandgap sections. By balancing the pump current in the four LEDs, we achieved 292 nm of 3 dB bandwidth and an on-chip power of -8 dBm. PMID- 25121876 TI - Parametric laser pulse shortening. AB - We report simultaneous laser pulse shortening and wavelength conversion based on spectral-temporal correlation in high-gain optical parametric generation (OPG). By spectrally filtering the off-peak signal energy, we shortened a 560 ps pump pulse at 1064 nm to an 80 ps signal pulse at 1.5 MUm from a 45 mm long PPLN optical parametric generator with 60 MUJ pump energy from a passively Q-switched Nd:YAG laser. Using the same technique, we further demonstrated a 3.6 time shortened laser pulse at 1072 nm from noncollinearly phase matched OPG in a 44 mm long lithium niobate crystal with 3 mJ amplified pump energy from the same Nd:YAG laser. PMID- 25121875 TI - Femtosecond pulse shaping enables detection of optical Kerr-effect (OKE) dynamics for molecular imaging. AB - We apply femtosecond pulse shaping to generate optical pulse trains that directly access a material's nonlinear refractive index (n2) and can thus determine time resolved optical Kerr-effect (OKE) dynamics. Two types of static pulse trains are discussed: The first uses two identical fields delayed in time, plus a pump field at a different wavelength. Time-resolved OKE dynamics are retrieved by monitoring the phase of the interference pattern produced by the two identical fields in the Fourier-domain (FD) as a function of pump-probe-time-delay (where the probe is one of the two identical fields). The second pulse train uses three fields with equal time delays, but with the center field phase shifted by pi/2. In this pulse scheme, changes on a sample's nonlinear refractive index produce a new frequency in the FD signal, which in turn yields background-free intensity changes in the conjugate (time) domain and provides superior signal-to-noise ratios. The demonstrated sensitivity improvements enable, for the first time to our knowledge, molecular imaging based on OKE dynamics. PMID- 25121877 TI - 3D-printed miniature gas cell for photoacoustic spectroscopy of trace gases. AB - A new methodology for the development of miniature photoacoustic trace gas sensors using 3D printing is presented. A near-infrared distributed feedback (DFB) laser is used together with a polymer-based gas cell, off-the-shelf fiber optic collimators, and a microelectromechanical system (MEMS) microphone to measure acetylene at 1532.83 nm. The resonance behavior of the miniature gas cell is analyzed using a theoretical and experimental approach, with a measured resonance frequency of 15.25 kHz and a Q-factor of 15. A minimum normalized noise equivalent absorption of 4.5*10(-9) W cm(-1) Hz(-1/2) is shown together with a 3sigma detection limit of 750 parts per billion (ppb) for signal averaging times of 35 s. The fiber-coupled delivery and miniature cost-effective cell design allows for use in multipoint and remote detection applications. PMID- 25121878 TI - Opto-mechanical probe for combining atomic force microscopy and optical near field surface analysis. AB - We have developed a new easy-to-use probe that can be used to combine atomic force microscopy (AFM) and scanning near-field optical microscopy (SNOM). We show that, using this device, the evanescent field, obtained by total internal reflection conditions in a prism, can be visualized by approaching the surface with the scanning tip. Furthermore, we were able to obtain simultaneous AFM and SNOM images of a standard test grating in air and in liquid. The lateral resolution in AFM and SNOM mode was estimated to be 45 and 160 nm, respectively. This new probe overcomes a number of limitations that commercial probes have, while yielding the same resolution. PMID- 25121879 TI - Suppression and splitting of modulational instability sidebands in periodically tapered optical fibers because of fourth-order dispersion. AB - We study the modulational instability induced by periodic variations of group velocity dispersion in the proximity of the zero dispersion point. Multiple instability peaks originating from parametric resonance coexist with the conventional modulation instability because of fourth-order dispersion, which in turn is suppressed by the oscillations of dispersion. Moreover, isolated unstable regions appear in the space of parameters because of imperfect phase matching. This confirms the dramatic effect of periodic tapering in the control and shaping of MI sidebands in optical fibers. PMID- 25121880 TI - Quantum correlation of fiber-based telecom-band photon pairs through standard loss and random media. AB - We study quantum correlation and interference of fiber-based telecom-band photon pairs with one photon of the pair experiencing multiple scattering in a random medium. We measure joint probability of two-photon detection for signal photon in a normal channel and idler photon in a channel, which is subjected to two independent conditions: standard loss (neutral density filter) and random media. We observe that both conditions degrade the correlation of signal and idler photons, and depolarization of the idler photon in random medium can enhance two photon interference at certain relative polarization angles. Our theoretical calculation on two-photon polarization correlation and interference as a function of mean free path is in agreement with our experiment data. We conclude that quantum correlation of a polarization-entangled photon pair is better preserved than a polarization-correlated photon pair as one photon of the pair scatters through a random medium. PMID- 25121881 TI - Optimization of multicore fiber for high-temperature sensing. AB - We demonstrate a novel high-temperature sensor using multicore fiber (MCF) spliced between two single-mode fibers. Launching light into such fiber chains creates a supermode interference pattern in the MCF that translates into a periodic modulation in the transmission spectrum. The spectrum shifts with changes in temperature and can be easily monitored in real time. This device is simple to fabricate and has been experimentally shown to operate at temperatures up to 1000 degrees C in a very stable manner. Through simulation, we have optimized the multicore fiber design for sharp spectral features and high overall transmission in the optical communications window. Comparison between the experiment and the simulation has also allowed determination of the thermo-optic coefficient of the MCF as a function of temperature. PMID- 25121882 TI - Measurement of group velocity dispersion in a solid-core photonic crystal fiber filled with a nematic liquid crystal. AB - Liquid crystal-filled photonic crystal fibers (PCFs) are promising candidates for electrically tunable integrated photonic devices. In this Letter, we present group velocity measurements on such fibers. A large mode area PCF, LMA8, was infiltrated with the liquid crystal mixture, E7. The measurements were performed with an interferometric setup. The fiber exhibits several spectral transmission windows in the visible wavelength regime that originate from the bandgap guiding mechanism. The dispersion of these windows is very unusual compared to typical fibers. Our measurements show that it can change from -2500 ps km(-1) nm(-1) to +2500 ps km(-1) nm(-1) within a spectral range of only 15 nm. This leads to multiple zero dispersion wavelengths in the visible wavelength range. PMID- 25121883 TI - Ultrafast laser inscription of mid-IR directional couplers for stellar interferometry. AB - We report the ultrafast laser fabrication and mid-IR characterization (3.39 MUm) of four-port evanescent field directional couplers. The couplers were fabricated in a commercial gallium lanthanum sulfide glass substrate using sub-picosecond laser pulses of 1030 nm light. Straight waveguides inscribed using optimal fabrication parameters were found to exhibit propagation losses of ~0.8 dB.cm( 1). A series of couplers were inscribed with different interaction lengths, and we demonstrate power-splitting ratios of between 8% and 99% for mid-IR light with a wavelength of 3.39 MUm. These results clearly demonstrate that ultrafast laser inscription can be used to fabricate high-quality evanescent field couplers for future applications in astronomical interferometry. PMID- 25121884 TI - Lattice plasmon resonance in core-shell SiO2/Au nanocylinder arrays. AB - Core-shell SiO2/Au nanocylinder arrays (NCAs) are studied using finite-difference time-domain simulations. The increase of height induces new surface plasmon resonances along the nanocylinders, i.e., dipole and quadrupole modes. Orthogonal coupling between superstrate diffraction order and the height-induced dipole mode is observed, which could achieve a well-defined lattice plasmon mode even for smaller NCAs in asymmetric environments. Electromagnetic field distribution has been employed to determine the coupling origin. Radiative loss could also be effectively suppressed in these core-shell NCAs, indicating the possibility of future applications in fluorescence enhancement and nanolasers. PMID- 25121885 TI - Comparison of T-matrix calculation methods for scattering by cylinders in optical tweezers. AB - The T-matrix method, or the T-matrix formulation of scattering, is a framework for mathematically describing the scattering properties of an object as a linear relationship between expansion coefficients of the incident and scattering fields in a basis of vector spherical wave functions (VSWFs). A variety of methods can be used to calculate the T-matrix. We explore the applicability of the extended boundary condition method (EBCM) and point matching (PM) method to calculate the T-matrix for scattering by cylinders in optical tweezers and hence the optical force acting on them. We compare both methods with the discrete-dipole approximation (DDA) to measure their accuracy for different sizes and aspect ratios (ARs) for Rayleigh and wavelength-size cylinders. We determine range of sizes and ARs giving errors below 1% and 10%. These results can help researchers choose the most efficient method to calculate the T-matrix for nonspherical particles with acceptable accuracy. PMID- 25121886 TI - Time-domain coherent anti-Stokes Raman scattering in terms of the time-delayed Yuratich equation. AB - We show that the increasingly popular nonlinear optical technique of time-domain coherent anti-Stokes Raman scattering (CARS), which is often viewed from the dynamical perspective of the semiclassical time-dependent third-order polarization, can also be studied by means of the time-delayed version of the Yuratich equation, so popular in traditional frequency-domain CARS. The method proves successful in explaining experimental results that are otherwise treated by means of numerical methods only. PMID- 25121888 TI - High-speed silicon modulator with band equalization. AB - Electro-optic modulation up to 70 Gbit/s has been demonstrated using a silicon Mach-Zehnder modulator with a bias voltage of -1.5 V. In a wide frequency range from DC, an increasing input impedance of the modulator was designed to equalize its electro-optic frequency response. Without a bias voltage, the 3 dB bandwidth was measured as 35 GHz and it is predicted to be as high as 55 GHz at -3 V bias. Frequency responses of the modulator operated with counter-propagating waves were tested to verify the proposed prediction model. PMID- 25121887 TI - Interferometric fiber-optic bending/nano-displacement sensor using plastic dual core fiber. AB - We demonstrate an interferometric fiber-optic bending/nano-displacement sensor based on a plastic dual-core fiber. The light coupled into the two fiber cores is first guided along the fiber, and then reflected by the mirror coated at the fiber end. Reflected light coming out of the fiber produces interference that shifts as the fiber bends. The interference shift is interrogated using a slit and a photodetector. The resolution of our sensor is ~3*10(-4) m(-1) for sensing the bending curvature, and ~70 nm for sensing the displacement. PMID- 25121889 TI - Mid-infrared digital holography and holographic interferometry with a tunable quantum cascade laser. AB - Mid-infrared digital holography based on CO2 lasers has proven to be a powerful coherent imaging technique due to reduced sensitivity to mechanical vibrations, increased field of view, high optical power, and possible vision through scattering media, e.g., smoke. Here we demonstrate a similar and more compact holographic system based on an external cavity quantum cascade laser emitting at 8 MUm. Such a setup, which includes a highly sensitive microbolometric camera, allows the acquisition of speckle holograms of scattering objects, which can be processed in real time. In addition, by exploiting the broad laser tunability, we can acquire holograms at different wavelengths, from which we extract phase images not subjected to phase wrapping, at synthetic wavelengths ranging from hundreds of micrometers to several millimeters. PMID- 25121890 TI - Optical limiting properties of a nonlinear multilayer Fabry-Perot resonator containing niobium pentoxide as nonlinear medium. AB - The optical limiting effect was numerically simulated and experimentally observed for a 25-layer thin-film Fabry-Perot microresonator by 7 ns laser pulses at 532 nm. The sample, made by vacuum evaporation and consisting of alternating Nb2O5 and SiO2 layers, has an ultranarrow line of transparency at near 532 nm within a wide spectral band of reflection. By adjusting simulated results in accordance with experimental dependencies of transmittance, reflectance, and absorbance on incident light intensity, the coefficient of optical nonlinearity of Nb2O5 was estimated at (6+1i).10(-12) cm2/W. PMID- 25121891 TI - Combining cw-seeding with highly nonlinear fibers in a broadly tunable femtosecond optical parametric amplifier at 42 MHz. AB - We report on a precisely tunable and highly stable femtosecond oscillator-pumped optical parametric amplifier at a 41.7 MHz repetition rate for spectroscopic applications. A novel concept based on cw-seeding of a first amplification stage with subsequent spectral broadening and shaping, followed by two further amplification stages, allows for precise sub-nanometer and gap-free tuning from 1.35 to 1.75 MUm and 2.55 to 4.5 MUm. Excellent spectral stability is demonstrated with deviations of less than 0.008% rms central wavelength and 1.6% rms bandwidth over 1 h. Spectral shaping of the seed pulse allows precise adjustment of both the bandwidth and the pulse duration over a broad range at a given central wavelength. Transform-limited pulses nearly as short as 107 fs are achieved. More than half a Watt of average power in the near- and more than 200 mW in the mid-infrared with power fluctuations less than 0.6% rms over 1 h provide an excellent basis for spectroscopic experiments. The pulse-to-pulse power fluctuations are as small as 1.8%. Further, we demonstrate for the first time, to the best of our knowledge, that by using hollow-core capillaries with highly nonlinear liquids as a host medium for self-phase modulation, the signal tuning range can be extended and covers the region from 1.4 MUm up to the point of degeneracy at 2.07 MUm. Hence, the idler covers 2.07 to 4.0 MUm. PMID- 25121892 TI - High-power flip-chip semiconductor disk laser in the 1.3 MUm wavelength band. AB - We present 6.1 W of output power from a flip-chip semiconductor disk laser (SDL) emitting in the 1.3 MUm wavelength region. This is the first demonstration of a flip-chip SDL in this wavelength range with output powers that are comparable to those obtained with intracavity diamond heat spreaders. The flip-chip configuration circumvents the optical distortions and losses that the intracavity diamond heat spreaders can introduce into the laser cavity. This is essential for several key applications of SDLs. PMID- 25121894 TI - Cost-efficient delay generator for fast terahertz imaging. AB - We present a fast and low-cost delay generator for terahertz (THz) waves that transfers a rotational motion of a transparent dielectric cube into an effective THz delay. The device is easily implemented in the THz beam path and allows for coherent sampling over 40 ps with a scan rate of hundreds of hertz. Furthermore, we show that our approach is particularly suitable for fast THz imaging. PMID- 25121893 TI - Implications of Raman scattering and phase noise on multiple four-wave mixing processes in an optical fiber. AB - Implications of spontaneous and stimulated Raman scattering (SSRS) and phase noise on the spatial evolution of multiple-order sidebands arising from four-wave mixing (FWM) along the length of an optical fiber are investigated. A modified split-step Fourier method is used to solve the governing coupled nonlinear Schrodinger equations. The phase noise overcomes the depletive nature of SSRS and stabilizes the FWM sidebands, in good agreement with experimental results. PMID- 25121895 TI - Plasmonic routing in aperiodic graphene sheet arrays. AB - We discover deep-subwavelength, low-loss, and diffraction-free surface plasmon polariton (SPP) beam routing effects in aperiodic graphene sheet arrays (a-GSAs). The a-GSAs are constructed by varying either the interlayer spaces between graphene or the individual graphene chemical potentials. The SPP beams can be accelerated or decelerated in the a-GSAs, resulting in beam routing in different paths. The wave fronts of the beams are always parallel to the propagation direction, allowing the generation of transverse radiation pressure. All of these behaviors of SPPs are demonstrated by fully vectorial simulation and Hamilton optics analysis. PMID- 25121896 TI - Miniature forward-viewing spectrally encoded endoscopic probe. AB - Spectrally encoded endoscopy is a promising technique for minimally invasive imaging, allowing high-quality imaging through small diameter probes that do not require rapid mechanical scanning. A novel optical configuration that employs broadband visible light and dual-channel imaging is used to demonstrate a miniature forward-viewing probe having a high number of resolvable points, low speckle contrast, negligible backreflections, and high signal-to-noise ratio. The system would be most suitable for imaging through narrow ducts and vessels for clinical diagnosis at hard-to-reach locations in the body. PMID- 25121897 TI - Remote wind sensing with a CW diode laser lidar beyond the coherence regime. AB - We experimentally demonstrate for the first time (to our knowledge) a coherent CW lidar system capable of wind speed measurement at a probing distance beyond the coherence regime of the light source. A side-by-side wind measurement was conducted on the field using two lidar systems with identical optical designs but different laser linewidths. While one system was operating within the coherence regime, the other was measuring at least 2.4 times the coherence range. The probing distance of both lidars is 85 m and the radial wind speed correlation was measured to be r2=0.965 between the two lidars at a sampling rate of 2 Hz. Based on our experimental results, we describe a practical guideline for designing a wind lidar operating beyond the coherence regime. PMID- 25121898 TI - Fingerprints of topological defects in a metasurface. AB - Singularity, representing a structurally stable topological defect (TD), plays a pivotal role in various physical systems. Here we theoretically present the fingerprints of TDs and uncover the resulting exotic optical properties in a tailored metasurface system. The presence of the TDs results in coherent perfect absorption, and dramatic optical property transition from slow to superluminal light behavior when the parameters cross the TD. Our investigation provides a new route to explore many phenomena of the TDs, extends the capabilities of metasurface, and offers benefits to develop potential nanophotonic applications based on the design of the metasurface. PMID- 25121899 TI - Giant optical forces in planar dielectric photonic metamaterials. AB - We demonstrate that resonant optical forces generated within all-dielectric planar photonic metamaterials at near-infrared illumination wavelengths can be an order of magnitude larger than in corresponding plasmonic metamaterials, reaching levels many tens of times greater than the force resulting from radiation pressure. This is made possible by the dielectric structures' freedom from Joule losses and the consequent ability to sustain Fano-resonances with high quality factors that are unachievable in plasmonic nanostructures. Dielectric nano optomechanical metamaterials can thus provide a functional platform for a range of novel dynamically controlled and self-adaptive nonlinear, tunable/switchable photonic metamaterials. PMID- 25121900 TI - Narsarsukite-structure fluorosilicate as a blue component for white LEDs: structural and optical properties. AB - A new blue-emitting phosphor, K2ScSi4O10F:Eu>2+ (KSSOF:Eu2+), was synthesized through a solid-state reaction. The structural and optical properties of KSSOF:Eu2+ phosphor, in addition to its thermal quenching and fabrication of white LEDs (WLEDs), were investigated for the first time. The phosphor showed broad blue emission, with a maximum at ~434 nm under near-ultraviolet excitation due to 5d->4f transition of the Eu2+ ion. The critical distance was calculated to be 12 A using the critical concentration of Eu2+ and Dexter's theory for energy transfer. WLEDs were fabricated by blending KSSOF:Eu2+, commercial Lu3Al5O12:Ce3+, and (Sr,Ca)AlSiN3:Eu2+ phosphors, showed a high color rendering index of 88 at a correlated color temperature of 4134 K under a forward bias current of 100 mA. PMID- 25121901 TI - Extended parametric gain range in photonic crystal fibers with strongly frequency dependent field distributions. AB - The parametric gain range of a degenerate four-wave mixing process is determined in the undepleted pump regime. The gain range is considered with and without taking the mode field distributions of the four-wave mixing components into account. It is found that the mode field distributions have to be included to evaluate the parametric gain correctly in dispersion-tailored speciality fibers and that mode profile engineering can provide a way to increase the parametric gain range. PMID- 25121902 TI - Narrow bandwidth, picosecond, 1064 nm pumped optical parametric generator for the mid-IR based on HgGa2S4. AB - We report on optical parametric generation in a mercury thiogallate (HgGa2S4) crystal pumped by 16 ps, 1064 nm pulses at 250 kHz. A broad tuning range extending from 1.19 to 1.47 MUm (signal) and from 3.85 to 10 MUm (idler) is achieved. Narrow bandwidth, quasi-Fourier limited operation with high beam quality for the signal/idler pulses and >14% pump depletion is obtained by continuous wave seed injection at 1.29 MUm. PMID- 25121903 TI - Bilayer holey plasmonic vortex lenses for the far field transmission of pure orbital angular momentum light states. AB - We report the design of a holey plasmonic vortex lens (PVL) structure able to couple circularly polarized impinging light to a plasmonic vortex in the form of the fundamental TM mode of a metal-insulator-metal plasmonic waveguide. The field transmitted through the hole milled at the center of the second metal layer of the structure is characterized by a well-defined spiral harmonic, entirely determined by the spin of impinging light and by the chirality of the PVL structure. Scattering finite elements simulations are presented for single layer standard PVLs and for bilayer ones, comparing the spiral spectra of the transmitted field and the efficiencies of the architectures. PMID- 25121904 TI - Noncontact photoacoustic imaging based on all-fiber heterodyne interferometer. AB - We report on a noncontact photoacoustic imaging system utilizing an all-fiber optic heterodyne interferometer as an acoustic wave detector. The acoustic wave generated by a short laser pulse via the photoacoustic effect and arriving at the sample surface could be detected with the fiber-optic heterodyne interferometer without physical contact or using an impedance matching medium. A phantom experiment was conducted to evaluate the proposed system, and the initial acoustic pressure distribution was calculated using a Fourier-based reconstruction algorithm. It is expected that the all-fiber-optic configuration of the proposed system can be applied as a minimally invasive diagnostic tool. PMID- 25121905 TI - Phase conjugation of vector fields by degenerate four-wave mixing in a Fe-doped LiNbO3. AB - We propose a method to generate the phase-conjugate wave of the vector field by degenerate four-wave mixing in a c-cut Fe-doped LiNbO3 crystal. We demonstrate experimentally that the phase-conjugate wave of the vector field can be generated. In particular, the phase-conjugate vector field has also the peculiar function of compensating the polarization distortion, as the traditional phase conjugate scaler field can compensate the phase distortion. PMID- 25121906 TI - Design of spatio-temporally modulated static infrared imaging Fourier transform spectrometer. AB - A novel static medium wave infrared (MWIR) imaging Fourier transform spectrometer (IFTS) is conceptually proposed and experimentally demonstrated. In this system, the moving mirror in traditional temporally modulated IFTS is replaced by multi step micro-mirrors to realize the static design. Compared with the traditional spatially modulated IFTS, they have no slit system and are superior with larger luminous flux and higher energy efficiency. The use of the multi-step micro mirrors can also make the system compact and light. PMID- 25121907 TI - Demonstration of tunable optical generation of higher-order modulation formats using nonlinearities and coherent frequency comb. AB - We demonstrate a tunable, optical generation scheme of higher-order modulation formats including pulse amplitude modulation (PAM) and quadrature amplitude modulation (QAM). Using this method, 100.4 Gbit/s 16-QAM and 120 Gbit/s 64-QAM were generated from 50.2 and 40 Gbit/s QPSK signals at EVMs of 7.8% and 6.4%, and 60 Gbit/s 8-PAM were generated at an EVM of 8.1% using three 20-Gbit/s BPSK signals. We also demonstrated a successful transmission of 80 Gbit/s 16-QAM through 80 km SMF-28 after compensating with 20 km DCF. All signals were generated, transmitted, and detected with BER below the forward error correction threshold. PMID- 25121908 TI - Suppression of nonlinear phonon relaxation in Yb:YAG thin disk via zero phonon line pumping. AB - A quantitative comparison of conventional absorption line (940 nm) pumping and zero phonon line (ZPL) (969 nm) pumping of a Yb:YAG thin disk laser is reported. Characteristics of an output beam profile, surface temperature, and deformation of a thin disk under the different pump wavelengths are evaluated. We found that a nonlinear phonon relaxation (NPR) of the excited state in Yb:YAG, which induces nonlinear temperature rise and large aspheric deformation, did not appear in the case of a ZPL pumped Yb:YAG thin disk. This means that the advantage of ZPL pumping is not only the reduction of quantum defect but also the suppression of NPR. The latter effect is more important for high power lasers. PMID- 25121909 TI - Precise frequency measurement and characterization of a continuous scanning single-mode laser with an optical frequency comb. AB - We developed a high-precision frequency-measurement system for continuously scanning single-mode cw lasers. The high precision for wide frequency range is realized by employing an optical frequency comb. The developed system operates as a strong tool for analyzing the spectral profile and scan characteristics of lasers, which is suitable for high-resolution molecular spectroscopy. We demonstrated the ability of our system with Doppler-free spectroscopy of molecular iodine. PMID- 25121910 TI - Using shadows to measure spatial coherence. AB - We present a very simple method for measuring the spatial coherence of quasi monochromatic fields through the comparison of two measurements of the radiant intensity with and without a small obscuration at the test plane. From these measurements one can measure simultaneously the field's coherence at all pairs of points whose centroid is the centroid of the obstacle. This method can be implemented without the need of any refractive or diffractive focusing elements. PMID- 25121911 TI - Experimental observation of lateral emission in freestanding GaN-based membrane devices. AB - This Letter describes a double-sided process to fabricate freestanding membrane devices on a GaN-on-silicon platform. The photoluminescence measurement is taken to characterize the optical performance. A large portion of the excited light from InGaN/GaN multiple quantum wells is trapped as waveguide modes and propagates in different directions. Experimental results show that the propagation direction of the waveguide mode can be converted into the direction normal to the surface at the edge of a freestanding membrane, and the emitted light is attenuated due to light propagation loss before it gets out from the edge. Subwavelength grating can also convert waveguide modes into air modes on a freestanding membrane. These results suggest that the emission efficiency can be greatly improved by employing more efficient light extraction methods and that GaN-based photonic waveguides are promising in the visible range. PMID- 25121912 TI - One-way optical transmission in silicon grating-photonic crystal structures. AB - One-way optical transmission through a composite structure of grating-photonic crystal (PC) is presented. This unidirectional transportation property originates from the diffraction of grating to change the direction of light incident into the PC from pseudobandgaps to passbands of the PC. Numerical simulation shows that a light beam in a certain range of frequencies can transmit the composite structure when it is incident from the grating interface but is completely reflected by the structure when it is incident from the PC interface, which is further verified experimentally. The present structure may provide another more compact way for designing on-chip optical diode-like integrated devices. PMID- 25121913 TI - All-optical modulation and switching by a metamaterial of plasmonic circuits. AB - We demonstrate experimentally the modulation and switching of one light beam by a second beam using metamaterials constructed from arrays of plasmonic circuits. Each circuit consists of three gold nanorods that mix together two coherent but orthogonally polarized light beams leading to modulation by an interference effect. By adjusting the phase and the amplitude of one of the beams, the amplitude and spectral composition of the second beam is altered. The plasmonic circuits display an asymmetry that enables an angle-dependent modulation, which we demonstrate with a diffraction grating where the energy directed into two diffraction orders is controlled by a second light beam. This effect appears like an optically controlled blaze that we use to switch a light beam between two different directions. PMID- 25121914 TI - Single-mode air-clad liquid-core waveguides on a surface energy patterned substrate. AB - We demonstrate a new kind of single-mode micro-optical waveguide based on a liquid core on top of solid substrate and air cladding. The liquid is held in place by surface tension and patterned surface energy on the substrate. Due to the smooth nature of the liquid/air interface down to the molecular level, low scattering losses are expected. Losses were measured to be -6.0 and -7.8 dB/cm for, respectively, 12 and 9 MUm wide waveguides. PMID- 25121915 TI - Narrow-linewidth quantum cascade laser at 8.6 MUm. AB - We report on a narrow-linewidth distributed-feedback quantum cascade laser at 8.6 MUm that is optical-feedback locked to a high-finesse V-shaped cavity. The spectral purity of the quantum cascade laser is fully characterized using a high sensitivity optical frequency discriminator, leading to a 1 ms linewidth of less than 4 kHz and a minimum laser frequency noise spectral density as low as 0.01 Hz2/Hz for Fourier frequencies larger than 100 kHz. The cumulative standard deviation of the laser intensity is better than 0.1% over an integration bandwidth from 2 Hz to 100 MHz. PMID- 25121917 TI - Tunable electro-optic filter based on metal-ferroelectric nanocomposite for VLC. AB - The emerging technology of visible light communications (VLC) will provide a new modality of communication. This technology uses illumination lighting to carry information. We propose to add a smart capability to mitigate interferences from unwanted light sources. This is achieved by adaptively filtering interference light using a tunable filter to block interferences dynamically. In this Letter, we present an innovative concept for a tunable notch filter based on ferroelectric thin films embedded with noble metal nanoparticles. The adaptivity of the filter is achieved by controlling the external applied voltage. This voltage creates an electric field that changes the refractive index of the host film through the linear electro-optic effect. Moreover, the fundamental characteristics of the filter are determined by the layer's parameters, such as film thickness, nanoparticles concentration and geometry, and the material of both the host thin film and nanoparticles. We study the tunability of lead zirconate titanate (PZT) embedded with Ag nanoparticles that reaches approximately 50 nm, between 530 and 590 nm. Moreover, we showed that a PZT notch filter embedded with Ag nanoshells has its stop band shifted to shorter wavelengths. These tunable filters can be used as mode selectors inside a laser resonator, spatial light filters for imaging and communication both for VLC and infrared communication. PMID- 25121916 TI - Generation of attenuation-compensating Airy beams. AB - We present an attenuation-corrected "nondiffracting" Airy beam. The correction factor can be adjusted to deliver a beam that exhibits an adjustable exponential intensity increase or decrease over a finite distance. A digital micromirror device that shapes both amplitude and phase is used to experimentally verify the propagation of these beams through air and partially absorbing media. PMID- 25121918 TI - Controlling high-power autofocusing waves with periodic lattices. AB - We show numerically that by using radial symmetric lattices, the focal spot characteristics and filament peak intensity of high-power autofocusing waves can be controlled. The lattice induced diffraction is able to isolate the main on axis peak and control the focus position. In addition, at higher power the lattice can control and stabilize the peak intensity of the filament over an extended distance. PMID- 25121919 TI - Efficient excitation of photoluminescence in a two-dimensional waveguide consisting of a quantum dot-polymer sandwich-type structure. AB - In this Letter, we study a new kind of organic polymer waveguide numerically and experimentally by combining an ultrathin (10-50 nm) layer of compactly packed CdSe/ZnS core/shell colloidal quantum dots (QDs) sandwiched between two cladding poly(methyl methacrylate) (PMMA) layers. When a pumping laser beam is coupled into the waveguide edge, light is mostly confined around the QD layer, improving the efficiency of excitation. Moreover, the absence of losses in the claddings allows the propagation of the pumping laser beam along the entire waveguide length; hence, a high-intensity photoluminescence (PL) is produced. Furthermore, a novel fabrication technology is developed to pattern the PMMA into ridge structures by UV lithography in order to provide additional light confinement. The sandwich-type waveguide is analyzed in comparison to a similar one formed by a PMMA film homogeneously doped by the same QDs. A 100-fold enhancement in the waveguided PL is found for the sandwich-type case due to the higher concentration of QDs inside the waveguide. PMID- 25121920 TI - Experimental observation of the effect of generic singularities in polychromatic dark hollow beams. AB - This Letter presents the essence of our recent experimental study on generic singularities carrying spatially partially coherent, polychromatic dark hollow beams (PDHBs). To the best of our knowledge, this is the first experimental demonstration of generic singularities-induced wavefront tearing in focused polychromatic beams. PMID- 25121921 TI - Polarization-diversified photonic comb filter with independently tunable free spectrum range. AB - A polarization-diversified photonic comb filter with tunable free spectrum range (FSR) is proposed using two variable differential group delay (DGD) elements in a loop configuration. Two different cosine transfer functions could be simultaneously realized on orthogonal polarization states. Experimental demonstrations also verify feasibilities in various reconfigurable transfer functions. PMID- 25121922 TI - Cascaded uncoupled dual-ring modulator. AB - We demonstrate, by coherent driving two uncoupled rings in same direction, that the effective photon circulating time in the dual-ring modulator is reduced, with increased modulation quality. The inter-ring detuning-dependent photon dynamics, Q factor, extinction ratio, and optical modulation amplitude of two cascaded silicon ring resonators are studied and compared with that of a single-ring modulator. Experimentally measured eye diagrams, together with coupled mode theory simulations, demonstrate the enhancement of the dual-ring configuration at 20 Gbps with a Q~20,000. PMID- 25121924 TI - Protein stable isotope fingerprinting: multidimensional protein chromatography coupled to stable isotope-ratio mass spectrometry. AB - Protein stable isotope fingerprinting (P-SIF) is a method to measure the carbon isotope ratios of whole proteins separated from complex mixtures, including cultures and environmental samples. The goal of P-SIF is to expose the links between taxonomic identity and metabolic function in microbial ecosystems. To accomplish this, two dimensions of chromatography are used in sequence to resolve a sample containing ca. 5-10 mg of mixed proteins into 960 fractions. Each fraction then is split in two aliquots: The first is digested with trypsin for peptide sequencing, while the second has its ratio of (13)C/(12)C (value of delta(13)C) measured in triplicate using an isotope-ratio mass spectrometer interfaced with a spooling wire microcombustion device. Data from cultured species show that bacteria have a narrow distribution of protein delta(13)C values within individual taxa (+/-0.7-1.20/00, 1sigma). This is moderately larger than the mean precision of the triplicate isotope measurements (+/-0.50/00, 1sigma) and may reflect heterogeneous distribution of (13)C among the amino acids. When cells from different species are mixed together prior to protein extraction and separation, the results can predict accurately (to within +/ 1sigma) the delta(13)C values of the original taxa. The number of data points required for this endmember prediction is >=20/taxon, yielding a theoretical resolution of ca. 10 taxonomic units/sample. Such resolution should be useful to determine the overall trophic breadth of mixed microbial ecosystems. Although we utilize P-SIF to measure natural isotope ratios, it also could be combined with experiments that incorporate stable isotope labeling. PMID- 25121925 TI - Concentration dependence of ionic hydration numbers. AB - Isothermal compressibility data of 23 aqueous electrolyte solutions at 25 degrees C from the literature are used to calculate their hydration numbers, which diminish as the concentration increases. Their limit at very high concentration is near the "number of adsorption sites" of water molecules on the ions, obtained by the BET method. On the contrary, hydration numbers obtained from ultrasound speed measurements yielding isentropic compressibilities cannot be valid, being much too large at infinite dilution. PMID- 25121923 TI - Wage, work environment, and staffing: effects on nurse outcomes. AB - Research has shown that hospitals with better nurse staffing and work environments have better nurse outcomes-less burnout, job dissatisfaction, and intention to leave the job. Many studies, however, have not accounted for wage effects, which may confound findings. By using a secondary analysis with cross sectional administrative data and a four-state survey of nurses, we investigated how wage, work environment, and staffing were associated with nurse outcomes. Logistic regression models, with and without wage, were used to estimate the effects of work environment and staffing on burnout, job dissatisfaction, and intent to leave. We discovered that wage was associated with job dissatisfaction and intent to leave but had little influence on burnout, while work environment and average patient-to-nurse ratio still have considerable effects on nurse outcomes. Wage is important for good nurse outcomes, but it does not diminish the significant influence of work environment and staffing on nurse outcomes. PMID- 25121927 TI - Incidence of steroid-induced ocular hypertension after vitreoretinal surgery with difluprednate versus prednisolone acetate. AB - PURPOSE: To identify changes in intraocular pressure (IOP) after vitreoretinal surgical procedures in eyes that received either difluprednate ophthalmic emulsion 0.05% (DP) or prednisolone acetate ophthalmic suspension 1% (PA). METHODS: A retrospective chart review compared a consecutive series of 100 patients who received DP with 100 patients who received PA after vitreoretinal surgery. Data were collected for a 3-month period from the time of surgery. RESULTS: A significantly higher number of patients treated with DP (35%, n = 35) developed increased IOP (>21 mmHg with a change from baseline of >10 mmHg) compared with those receiving PA (22%, n = 22) (P = 0.042). The mean maximum IOP in the DP cohort (26.7 mmHg) was significantly higher than that in the PA cohort (22.8 mmHg) (P = 0.0027). Additionally, the rise in IOP from baseline was significantly higher in the DP-treated cohort (9.0 mmHg) than that in the PA treated cohort (6.0 mmHg) (P = 0.027). CONCLUSION: Eyes treated with DP after vitreoretinal surgery were at increased risk for developing clinically significant increases in IOP compared with those receiving PA. PMID- 25121928 TI - Visual and anatomical outcomes of macular epiretinal membrane peeling after previous rhegmatogenous retinal detachment repair. AB - PURPOSE: To report outcomes and prognostic factors after epiretinal membrane peeling in patients with previous rhegmatogenous retinal detachment repair. METHODS: A consecutive case series. Best-corrected visual acuity and optical coherence tomography characteristics were analyzed before and after epiretinal membrane surgery. RESULTS: Fifty-three eyes were analyzed. Best-corrected visual acuity improved by a mean of 10 letters at 1 month (N = 45; P = 0.001), 15 at 3 months (N = 42; P < 0.001), 11 at 6 months (N = 35; P = 0.001), and 16 at 12 months (N = 33; P < 0.001). The mean optical coherence tomography central foveal thickness decreased by 141 (N = 22; P < 0.001), 185 (N = 24; P < 0.001), 180 (N = 17; P = 0.001), and 151 MUm (N = 9; P = 0.017) at 1, 3, 6, and 12 months, respectively. Better preoperative best-corrected visual acuity correlated with better best-corrected visual acuity at all follow-up visits (P <= 0.001). Intact preoperative inner segment/outer segment junction and external limiting membrane line, but not the change in central foveal thickness or location of fluid, correlated with better postoperative best-corrected visual acuity through 6 months. CONCLUSION: Epiretinal membrane peeling after previous rhegmatogenous retinal detachment repair resulted in significant improvements in visual acuity and optical coherence tomography thickness, even in eyes with previous macula involving rhegmatogenous retinal detachment. Better preoperative visual acuity and intact outer retinal layers by optical coherence tomography were the main prognostic factors for visual outcomes. PMID- 25121929 TI - Diagnostic and therapeutic challenges. PMID- 25121926 TI - Cholesterol selectively regulates IL-5 induced mitogen activated protein kinase signaling in human eosinophils. AB - Eosinophils function contributes to human allergic and autoimmune diseases, many of which currently lack curative treatment. Development of more effective treatments for eosinophil-related diseases requires expanded understanding of eosinophil signaling and biology. Cell signaling requires integration of extracellular signals with intracellular responses, and is organized in part by cholesterol rich membrane microdomains (CRMMs), commonly referred to as lipid rafts. Formation of these organizational membrane domains is in turn dependent upon the amount of available cholesterol, which can fluctuate widely with a variety of disease states. We tested the hypothesis that manipulating membrane cholesterol content in primary human peripheral blood eosinophils (PBEos) would selectively alter signaling pathways that depend upon membrane-anchored signaling proteins localized within CRMMs (e.g., mitogen activated protein kinase [MAPK] pathway), while not affecting pathways that signal through soluble proteins, like the Janus Kinase/Signal Transducer and Activator of Transcription [JAK/STAT] pathway. Cholesterol levels were increased or decreased utilizing cholesterol chelating methyl-beta-cyclodextrin (MbetaCD), which can either extract membrane cholesterol or add exogenous membrane cholesterol depending on whether MbetaCD is preloaded with cholesterol. Human PBEos were pretreated with MbetaCD (cholesterol removal) or MbetaCD+Cholesterol (MbetaCD+Chol; cholesterol delivery); subsequent IL-5-stimulated signaling and physiological endpoints were assessed. MbetaCD reduced membrane cholesterol in PBEos, and attenuated an IL-5-stimulated p38 and extracellular-regulated kinase 1/2 phosphorylation (p-p38, p-ERK1/2), and an IL-5 dependent increase in interleukin-1beta (IL-1beta) mRNA levels. In contrast, MbetaCD+Chol treatment elevated PBEos membrane cholesterol levels and basal p p38, but did not alter IL-5-stimulated phosphorylation of ERK1/2, STAT5, or STAT3. Furthermore, MbetaCD+Chol pretreatment attenuated an IL-5-induced increase in cell survival at 48 hours, measured as total cellular metabolism. The reduction in cell survival following cholesterol addition despite unaltered STAT phosphorylation contradicts the current dogma in which JAK/STAT activation is sufficient to promote eosinophil survival, and suggests an additional, unidentified mechanism critically regulates IL-5-mediated human PBEos survival. PMID- 25121930 TI - Impact of duration of macula-off retinal detachment on visual outcome: a systematic review and meta-analysis of literature. AB - PURPOSE: To systematically review the influence of the lag time between macula off retinal detachment and surgical intervention on postoperative visual acuity as main outcome measure. METHODS: Systematic review and meta-analysis of articles published from 1995 to October 2013 of patients with macula-off retinal detachment and treated with scleral buckling or pars plana vitrectomy. Eligible data were pooled in a meta-analysis, analyzing the odds ratio between different durations of <= 3, <= 4, <= 7, and <= 10 days, comparing a final visual acuity of <= 0.4 logMAR with >0.4 logMAR, using a random-effects model. Last, the number needed to treat was calculated. RESULTS: Fourteen articles were eligible, of which 9 studies contained data that were suitable for meta-analysis. Patients who were operated with scleral buckling (n = 602) within 3 days since macular detachment had a statistically significant better chance of reaching a final visual acuity of 0.4 logMAR or better compared with a longer duration of macular detachment, with an odds ratio for <= 3 days versus 4 days to 7 days of 2.86 (95% confidence interval, 1.37-5.99) and an odds ratio for <= 3 days versus >3 days of 3.09 (95% confidence interval, 1.56-6.12), and with a number needed to treat of 4. For pars plana vitrectomy, the limited amount of data precluded a meta analysis with substantial results. CONCLUSION: This meta-analysis suggests that scleral buckling for macular detachment must preferably be performed within 3 days to optimize visual outcome. PMID- 25121931 TI - Preoperative carbohydrate treatment for enhancing recovery after elective surgery. AB - BACKGROUND: Preoperative carbohydrate treatments have been widely adopted as part of enhanced recovery after surgery (ERAS) or fast-track surgery protocols. Although fast-track surgery protocols have been widely investigated and have been shown to be associated with improved postoperative outcomes, some individual constituents of these protocols, including preoperative carbohydrate treatment, have not been subject to such robust analysis. OBJECTIVES: To assess the effects of preoperative carbohydrate treatment, compared with placebo or preoperative fasting, on postoperative recovery and insulin resistance in adult patients undergoing elective surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 3), MEDLINE (January 1946 to March 2014), EMBASE (January 1947 to March 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1980 to March 2014) and Web of Science (January 1900 to March 2014) databases. We did not apply language restrictions in the literature search. We searched reference lists of relevant articles and contacted known authors in the field to identify unpublished data. SELECTION CRITERIA: We included all randomized controlled trials of preoperative carbohydrate treatment compared with placebo or traditional preoperative fasting in adult study participants undergoing elective surgery. Treatment groups needed to receive at least 45 g of carbohydrates within four hours before surgery or anaesthesia start time. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by at least two review authors, with discrepancies resolved by consensus. Data were abstracted and documented pro forma and were entered into RevMan 5.2 for analysis. Quality assessment was performed independently by two review authors according to the standard methodological procedures expected by The Cochrane Collaboration. When available data were insufficient for quality assessment or data analysis, trial authors were contacted to request needed information. We collected trial data on complication rates and aspiration pneumonitis. MAIN RESULTS: We included 27 trials involving 1976 participants Trials were conducted in Europe, China, Brazil, Canada and New Zealand and involved patients undergoing elective abdominal surgery (18), orthopaedic surgery (4), cardiac surgery (4) and thyroidectomy (1). Twelve studies were limited to participants with an American Society of Anaesthesiologists grade of I-II or I III.A total of 17 trials contained at least one domain judged to be at high risk of bias, and only two studies were judged to be at low risk of bias across all domains. Of greatest concern was the risk of bias associated with inadequate blinding, as most of the outcomes assessed by this review were subjective. Only six trials were judged to be at low risk of bias because of blinding.In 19 trials including 1351 participants, preoperative carbohydrate treatment was associated with shortened length of hospital stay compared with placebo or fasting (by 0.30 days; 95% confidence interval (CI) 0.56 to 0.04; very low-quality evidence). No significant effect on length of stay was noted when preoperative carbohydrate treatment was compared with placebo (14 trials including 867 participants; mean difference -0.13 days; 95% CI -0.38 to 0.12). Based on two trials including 86 participants, preoperative carbohydrate treatment was also associated with shortened time to passage of flatus when compared with placebo or fasting (by 0.39 days; 95% CI 0.70 to 0.07), as well as increased postoperative peripheral insulin sensitivity (three trials including 41 participants; mean increase in glucose infusion rate measured by hyperinsulinaemic euglycaemic clamp of 0.76 mg/kg/min; 95% CI 0.24 to 1.29; high-quality evidence).As reported by 14 trials involving 913 participants, preoperative carbohydrate treatment was not associated with an increase or a decrease in the risk of postoperative complications compared with placebo or fasting (risk ratio of complications 0.98, 95% CI 0.86 to 1.11; low-quality evidence). Aspiration pneumonitis was not reported in any patients, regardless of treatment group allocation. AUTHORS' CONCLUSIONS: Preoperative carbohydrate treatment was associated with a small reduction in length of hospital stay when compared with placebo or fasting in adult patients undergoing elective surgery. It was found that preoperative carbohydrate treatment did not increase or decrease postoperative complication rates when compared with placebo or fasting. Lack of adequate blinding in many studies may have contributed to observed treatment effects for these subjective outcomes, which are subject to possible biases. PMID- 25121933 TI - Registered nurses, nurse specialists and physicians have a neutral to moderately positive view on nurse prescribing, though physicians still have patient safety concerns. AB - Implications for practice and research: The process of assigning medical roles to nurses has to be gradual and stepwise. The influence of this process on the consequences for the nursing and medical professions, and for the quality of care, should be investigated further. PMID- 25121934 TI - Nurse home visits for infants and toddlers of low-income families improve behavioural, language and attention outcomes at age 6-9 years; paraprofessional visits improve visual attention and task switching. AB - Implications for practice and research: Infant home visiting can be efficacious in improving child developmental outcomes throughout early childhood. Home visiting by trained nurses produce positive outcomes, whereas outcomes for paraprofessionals are mixed. This study suggests that future research should be directed towards understanding how nurses have a more positive impact on mothers and their children than paraprofessionals. PMID- 25121935 TI - Health professionals' pain management decisions are influenced by their role (nurse or physician) and by patient gender, age and ethnicity. AB - Implications for practice and research: Healthcare providers from different fields may respond differently to patients with pain. On average, nurses rated pain intensity higher than physicians and were more likely to prescribe opioids. Patient demographic characteristics may influence nurses' and physicians' perceptions of pain intensity and decisions to treat pain with opioid analgesics. This study must be replicated with a more robust study design before findings can be translated into recommendations for intervention. PMID- 25121936 TI - High prevalence of neck, shoulder and back pain among nursing graduates warrants preventive strategies during the degree and into working life. AB - Implications for practice and research: Physical, organisational and social aspects of work significantly contribute to musculoskeletal pain in nurses, along with nonoccupational contextual and personal factors. Measures to prevent neck, shoulder and back pain in nurses should be implemented for nurses from the very beginning of their training programmes, while modifications to overtime work and physical loads should be seriously considered. Preventive measures targeting overtime work, physical workload and psychosocial factors need investigating further. PMID- 25121937 TI - Magnetic reflectometry of heterostructures. AB - Measuring the magnetic configuration at complex buried layers and interfaces is an important task, which requires especially a non-destructive probing technique. X-ray resonant magnetic reflectometry (XRMR) combines the non-destructive depth profiling potential of x-ray reflectometry with the excellent sensitivity for magnetic phenomena, utilizing the x-ray magnetic circular dichroism effect. It provides the magnetic spatial distribution with a precision down to the angstrom scale, combined with element and symmetry specificity, sub-monolayer sensitivity, and the possible separation of spin and orbital magnetic moments. This review provides an overview to the XRMR technique in a tutorial way. We focus on the introduction to the theory, measurement types, and data simulation. We provide related experimental examples and show selected applications. PMID- 25121932 TI - Conditional inactivation of Upstream Binding Factor reveals its epigenetic functions and the existence of a somatic nucleolar precursor body. AB - Upstream Binding Factor (UBF) is a unique multi-HMGB-box protein first identified as a co-factor in RNA polymerase I (RPI/PolI) transcription. However, its poor DNA sequence selectivity and its ability to generate nucleosome-like nucleoprotein complexes suggest a more generalized role in chromatin structure. We previously showed that extensive depletion of UBF reduced the number of actively transcribed ribosomal RNA (rRNA) genes, but had little effect on rRNA synthesis rates or cell proliferation, leaving open the question of its requirement for RPI transcription. Using gene deletion in mouse, we now show that UBF is essential for embryo development beyond morula. Conditional deletion in cell cultures reveals that UBF is also essential for transcription of the rRNA genes and that it defines the active chromatin conformation of both gene and enhancer sequences. Loss of UBF prevents formation of the SL1/TIF1B pre initiation complex and recruitment of the RPI-Rrn3/TIF1A complex. It is also accompanied by recruitment of H3K9me3, canonical histone H1 and HP1alpha, but not by de novo DNA methylation. Further, genes retain penta-acetyl H4 and H2A.Z, suggesting that even in the absence of UBF the rRNA genes can maintain a potentially active state. In contrast to canonical histone H1, binding of H1.4 is dependent on UBF, strongly suggesting that it plays a positive role in gene activity. Unexpectedly, arrest of rRNA synthesis does not suppress transcription of the 5S, tRNA or snRNA genes, nor expression of the several hundred mRNA genes implicated in ribosome biogenesis. Thus, rRNA gene activity does not coordinate global gene expression for ribosome biogenesis. Loss of UBF also unexpectedly induced the formation in cells of a large sub-nuclear structure resembling the nucleolar precursor body (NPB) of oocytes and early embryos. These somatic NPBs contain rRNA synthesis and processing factors but do not associate with the rRNA gene loci (NORs). PMID- 25121938 TI - Objective evaluation of elbow flexion strength and fatigability after nerve transfer in adult traumatic upper brachial plexus injuries. AB - Nerve transfers Oberlin-type are currently used in upper brachial plexus lesions to recover elbow flexion. Is the regained active motion sufficient to resume heavy manual activities? Five adult patients (mean age 37 years) operated of a nerve transfer to recover elbow flexion (transfer of a motor fascicle of the ulnar nerve to the motor branch of the biceps; in three patients, additional transfer from the median to the motor nerve of the brachialis) were clinically and isokinetically evaluated, after a mean follow-up of 47 months. The median Constant-Murley score was 22/100, the DASH 56/100 and the MEPI 60/100. For isokinetic tests the most significant finding was a severe deficit of elbow strength, of about 80%. No patient was able to maintain an isometric contraction during sufficient time to evaluate fatigability. This preliminary study suggests that major functional impairments persist despite early recovery of elbow flexion. These results should be confirmed in a study on a larger group of patients. PMID- 25121939 TI - Coronal fracture of the scaphoid--a case report and literature review. AB - Coronal fracture of the scaphoid is a rare configuration of scaphoid fracture. Only three cases have been found to be reported in English literature. In our case, a 25-year-old man sustained right wrist injury after a fall with an outstretched hand, was suspected of suffering from a scaphoid fracture as shown on the pre-operative plain radiograph. Coronal fracture of the patient's scaphoid was found intra-operatively and was fixed with two headless compression screws in dorsal-to-volar direction. Post-operative outcome was clinically good as patient was symptom-free, and a computed tomography and radiograph showed complete healing of the fracture with no sign of avascular necrosis. PMID- 25121940 TI - Wrist rhythm during wrist joint motion evaluated by dynamic radiography. AB - We hypothesized that wrist joint motion involves a "wrist rhythm" similar to the scapulohumeral rhythm. Therefore, we used a flat-panel detector to evaluate the ratio of radiolunate and capitolunate joint motions during wrist joint motion by dynamic radiography. The subjects were 20 healthy men. Dynamic imaging of the wrist joint was performed during active exercise for a total of ten seconds. In this study, we defined the radiocarpal (RL angle) and midcarpal joint angle (CL angle) as the wrist joint angle in the obtained images and measured the variation of these angles. The average curve was plotted and regression lines calculated from the average curve. The ratio was calculated from the slopes of the regression lines of the RL CL angles. These findings indicated that the ratio of the RL and CL angle motions was approximately 1:4 during palmar flexion and approximately 2:1 during dorsiflexion. PMID- 25121941 TI - Bilateral bipartite carpal scaphoid: a case report and literature review. AB - Congenital bipartite carpal scaphoid has been reported as an extremely rare congenital anomaly. We report a case of a 47-year-old man who was found with bilateral bipartite carpal scaphoids with no history of injury. Radiographs demonstrated symmetric findings of the distinct bipartition of the scaphoid without obvious degenerative change in both wrists. The patient complained of no other symptoms. The diagnostic differentiation of scaphoid bipartition from the pseudarthrosis of the scaphoid could be important in avoiding unnecessary surgery and inappropriate assessment in compensation cases. PMID- 25121942 TI - Modified Brunelli pull-out suture technique in zone II flexor tendon rupture: a fresh human cadaver study. AB - PURPOSE: The aim of our study is to develop a suture technique that has sufficient strength of active mobilization. METHODS: Thirty two fingers of six fresh human cadavers were divided into two groups. Flexor digitorum profundus (FDP) tendons in the study group were repaired by modified Brunelli suture technique and modified Kessler suture technique, while those in the control group were repaired by Modified Kessler suture technique. Flexion and extension movements were performed with 10 N of load, increasing 1 N at a time to the tendons in both groups. Rupture and significant gap formation was evaluated up to 20 N of load. In the study, to evaluate the resistance to active motion, 1000 times flexion and extension motion cycle was performed with a load of 20 N. The succeeding repaired tendons was also tested with flexion and extension movements increasing the load 1 N at a time. RESULTS: In the study group, failure and significant gap formation on the repair zone were not observed after 20 N of load and 1000 times cyclic flexion and extension movements for resisting to active motion. The rupture and significant gap formation was observed on a average load of 98.43 +/- 0.47 N. In the Modified Kessler suture technique, on the eight tendons before reaching the 20 N of load for resisting to active motion, and the remaining eight tendons, during the 20 N loaded motion cycle essential for active motion, rupture and significant gap formation was observed. The failure and significant gap formation was observed on a average load of 18.37 +/- 1.89 N. It is measured that by accompanying Modified Brunelli suture to the Modified Kessler suture technique, the resistance was increased up to 5-6 times. DISCUSSION: By the Modified Brunelli suture technique, active motion can be started to the finger without a dorsal block sling immediately after the surgery. Clinical Relavans: By the modified technique, the rehabilitation difficulty and joint stiffness will be minimized. PMID- 25121943 TI - Locking finger due to a partial laceration of the flexor digitorum superficialis tendon: a case report. AB - A 39-year-old woman sustained a small wound on the palm of her right hand, which quickly healed naturally; however, a month later pain and limited range of motion were noted in her right finger. Surgery revealed the radial half of the flexor digitorum superficialis (FDS) tendon was ruptured and formed a flap, which hooked at the entrance of the A1 pulley. The proximal stump was sutured to the remaining ulnar (normal) side of the FDS tendon. Locking occurs between the tendon flap and the tendon sheath; therefore, when there is no fibrous tendon sheath near the partially ruptured tendon, locking will not occur. PMID- 25121944 TI - Volar perilunate trans-scaphoid dislocation: a case. AB - We report a rare case of volar perilunate trans-scaphoid dislocation that was treated with open reduction and internal fixation. PMID- 25121945 TI - Associations between ulnar nerve strain and accompanying conditions in patients with cubital tunnel syndrome. AB - Pathophysiology of cubital tunnel syndrome (CubTS) is still controversial. Ulnar nerve strain at the elbow was measured intraoperatively in 13 patients with CubTS before simple decompression. The patients were divided into three groups according to their accompanying conditions: compression/adhesion, idiopathic, and relaxation groups. The mean ulnar nerve strain was 43.5 +/- 30.0%, 25.5 +/- 14.8%, and 9.0 +/- 5.0% in the compression/adhesion, idiopathic, and relaxation groups respectively. The mean ulnar nerve strains in patients with McGowan's classification grades I, II, and III were 18.0 +/- 4.2%, 27.1 +/- 22.7%, and 33.7 +/- 24.7%, respectively. The Jonckheere-Terpstra test showed that there were significant reductions in the ulnar nerve strain among the first three groups, but not in the three groups according to McGowan's classification. Our results suggest that the pathophysiology, not disease severity, of CubTS may be explained at least in part by the presence of ulnar nerve strain. PMID- 25121946 TI - Treatment of hook of the hamate fractures in adults using low-intensity pulsed ultrasound. AB - Two delayed unions and one nonunion of hook of the hamate fractures in adults aged 31-, 40-, and 41-years-old were treated with low-intensity pulsed ultrasound (LIPUS). Ultrasound treatment was started at three, four, and six months after injury and ultrasound exposure at the hook of the hamate in the hypothenar eminence was carried out for four to five months. During the management period, there was no immobilisation with a cast or brace and limited strain with only routine daily activities allowed. In all cases, bony union was confirmed on carpal tunnel radiographs or computed tomography at the final follow-up time of eight and 36 months after injuries. PMID- 25121947 TI - Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1. AB - The immunocytes that regulate papillomavirus infection and lesion development in humans and animals remain largely undefined. We found that immunocompetent mice with varying H-2 haplotypes displayed asymptomatic skin infection that produced L1 when challenged with 6*1010 MusPV1 virions, the recently identified domestic mouse papillomavirus (also designated "MmuPV1"), but were uniformly resistant to MusPV1-induced papillomatosis. Broad immunosuppression with cyclosporin A resulted in variable induction of papillomas after experimental infection with a similar dose, from robust in Cr:ORL SENCAR to none in C57BL/6 mice, with lesional outgrowth correlating with early viral gene expression and partly with reported strain-specific susceptibility to chemical carcinogens, but not with H-2 haplotype. Challenge with 1*1012 virions in the absence of immunosuppression induced small transient papillomas in Cr:ORL SENCAR but not in C57BL/6 mice. Antibody-induced depletion of CD3+ T cells permitted efficient virus replication and papilloma formation in both strains, providing experimental proof for the crucial role of T cells in controlling papillomavirus infection and associated disease. In Cr:ORL SENCAR mice, immunodepletion of either CD4+ or CD8+ T cells was sufficient for efficient infection and papillomatosis, although deletion of one subset did not inhibit the recruitment of the other subset to the infected epithelium. Thus, the functional cooperation of CD4+ and CD8+ T cells is required to protect this strain. In contrast, C57BL/6 mice required depletion of both CD4+ and CD8+ T cells for infection and papillomatosis, and separate CD4 knock-out and CD8 knock-out C57BL/6 were also resistant. Thus, in C57BL/6 mice, either CD4+ or CD8+ T cell-independent mechanisms exist that can protect this particular strain from MusPV1-associated disease. These findings may help to explain the diversity of pathological outcomes in immunocompetent humans after infection with a specific human papillomavirus genotype. PMID- 25121948 TI - Predictive clinical indicators of biochemical progression in advanced prostate cancer patients receiving Leuplin depot as androgen deprivation therapy. AB - Therapeutic planning and counseling for advanced prostate cancer patients receiving androgen deprivation therapy (ADT) is complicated because the prognoses are highly variable. The purpose of this study is to identify predictive clinical indicators of biochemical progression (BCP). In this retrospective analysis, data from 107 newly diagnosed patients (from November 1995 to April 2008) with advanced prostate adenocarcinoma receiving Leuprorelin acetate depot were analyzed. Data was collected from the computerized registry of two collaborating medical centers in Taiwan. Cox regression and Kaplan-Meier analyses were used to evaluate the relationship between potential predictive parameters and BCP. Univariate analysis revealed that predictors of BCP included (1) initial serum prostate-specific antigen (PSA) (hazard ratio [HR], 1.00; 95% confidence interval [CI] 1.00-1.00); (2) log of initial PSA (HR, 1.35; 95% CI 1.17-1.56); (3) PSA density at diagnosis (HR, 1.00; 95% CI 1.00-1.01), and (4) pathological bone fracture (HR, 2.22; 95% CI 1.20-4.11). Age (HR, 0.94; 95% CI 0.91-0.98) and hemoglobin levels (HR, 0.86; 95% CI 0.76-0.97) were also associated with greater risk of BCP. After adjusting for age, pathologic fracture, and hemoglobin level, the initial PSA and PSA density were no longer significantly associated with BCP. However, age and hemoglobin levels continued to be associated with greater risk of BCP (P <= 0.007). Using Kaplan-Meier analysis, patients with higher initial PSA concentration, pathological bone fracture, and low hemoglobin had a greater probability of BCP. Thus, low hemoglobin and age are predictive indicators of BCP and therefore early indicators of BCP despite ADT therapy. PMID- 25121950 TI - CE: Champions for central line care. AB - OVERVIEW: In 2012, acute care hospitals in the United States reported 30,100 central line-associated bloodstream infections (CLABSIs) to the National Healthcare Safety Network of the Centers for Disease Control and Prevention. Known to substantially increase morbidity, length of stay, and cost of care, CLABSIs are associated with a mortality rate of 12% to 25% and an additional cost of $22,885 to $29,330 per incident. Following five months with a sustained CLABSI rate of zero per 1,000 catheter days, the acuity adaptable critical care unit at Geisinger Medical Center in Danville, Pennsylvania, saw the CLABSI rate spike to 3.97 per 1,000 catheter days in March 2011, prompting a quality improvement project and, ultimately, the implementation within the unit of a champion team program to guide central line care. PMID- 25121949 TI - CE: Original Research: Staff nurses' use of research to facilitate evidence-based practice. AB - OBJECTIVES: To determine to what extent RNs in an acute care multihospital system used research findings in their practice; what types of knowledge they used in their practice; and what personal, professional, and organizational factors enhanced or hindered their research utilization. METHODS: A cross-sectional, descriptive, online survey design was used. The survey, which asked about use of research findings in practice and evidence-based practice (EBP) participation, was placed on the hospital system intranet. Of the 2,900 RNs invited to participate, 1,112 nurses completed usable surveys, for a response rate of 38%. This article reports findings for 794 of the staff nurses who responded to the survey. RESULTS: The forms of knowledge that staff nurses reported relying on most were their personal experience with patients, conferences, hospital policies and procedures, physician colleagues, and nursing peers. Although a variety of resources were available for nurses to use in locating research and implementing EBP, respondents reported many of the same barriers that have been reported in other studies over the last two decades: lack of time, lack of resources, and lack of knowledge. Although their attitudes about research utilization and EBP were positive overall, respondents expected unit-based educators and clinical nurse specialists to collect and synthesize the research for them. CONCLUSIONS: These findings are similar to those of other recent studies regarding nurses' research utilization and EBP. A great deal of work remains to be done if we are to inform, educate, and assist staff nurses in using research and implementing EBP. It may be unrealistic to expect bedside nurses to add these activities to their duties unless they are compensated for the time and have the support of master's or doctorally prepared nurses to serve as EBP coaches and champions. PMID- 25121952 TI - Response to comment on 'Preoperative nomogram for the identification of lymph node metastasis in early cervical cancer'. PMID- 25121951 TI - Operational momentum in multiplication and division? AB - Biases are commonly seen in numerical cognition. The operational momentum (OM) effect shows that responses to addition and subtraction problems are biased in the whole-number direction of the operation. It is not known if this bias exists for other arithmetic operations. To determine whether OM exists in scalar operations, we measured response bias in adults performing symbolic (Arabic digits) and non-symbolic (dots) multiplication and division problems. After seeing two operands, with either a multiplication (*) or division (/) sign, participants chose among five response choices. Both non-random performance profiles and the significant contribution of both operands in a multiple regression analysis predicting the chosen values, suggest that adults were able to use numerical information to approximate the outcomes in both notations, though they were more accurate on symbolic problems. Performance on non-symbolic problems was influenced by the size of the correct choice relative to alternatives. Reminiscent of the bias in addition and subtraction, we found a significant response bias for non-symbolic problems. Non-symbolic multiplication problems were overestimated and division problems were underestimated. These results indicate that operational momentum is present in non-symbolic multiplication and division. Given the influence of the size of the correct choice relative to alternatives, an interaction between heuristic bias and approximate calculation is possible. PMID- 25121953 TI - Overdiagnosis due to breast cancer screening: updated estimates of the Helsinki service study in Finland. AB - BACKGROUND: Overdiagnosis is the most important adverse event of breast cancer screening with the estimates ranging from 0% to 40-50% depending on invitational age and methods. We updated the estimates of overdiagnosis in Helsinki service screening study in Finland by comparing the observed and expected cumulative incidence of all breast carcinomas and invasive breast carcinomas. METHODS: Women aged 50-59 years have been invited to Helsinki service screening since 1986. The incidence of breast carcinoma in the first invited birth cohorts born in 1935 1939 was compared with older, non-invited cohorts. The minimum follow-up time of the invitees after the last screening round was 14 years. Expected cumulative incidence rates were estimated with two alternative approaches. RESULTS: For both any breast carcinoma and invasive breast carcinoma, the estimates of overdiagnosis varied from 5% (95% CI=-1, 11%) to 7% (95% CI=1, 13%) depending on the approach. CONCLUSIONS: Our estimates of overdiagnosis are of the same magnitude than other plausible estimates in Europe. Both alternative approaches produced similar estimates for the expected cumulative incidence, which increased the confidence in the estimates of overdiagnosis. PMID- 25121954 TI - Comment on 'Pre-operative nomogram for the identification of lymph node metastasis in early cervical cancer'. PMID- 25121958 TI - Transition-state structure for the quintessential SN2 reaction of a carbohydrate: reaction of alpha-glucopyranosyl fluoride with azide ion in water. AB - We report that the SN2 reaction of alpha-d-glucopyranosyl fluoride with azide ion proceeds through a loose (exploded) transition-state (TS) structure. We reached this conclusion by modeling the TS using a suite of five experimental kinetic isotope effects (KIEs) as constraints for the calculations. We also report that the anomeric (13)C-KIE is not abnormally large (k12/k13 = 1.024 +/- 0.006), a finding which is at variance with the previous literature value (Zhang et al. J. Am. Chem. Soc. 1994, 116, 7557). PMID- 25121956 TI - Serum protein profiling reveals baseline and pharmacodynamic biomarker signatures associated with clinical outcome in mCRC patients treated with chemotherapy +/- cediranib. AB - BACKGROUND: This study evaluated soluble serum proteins as biomarkers to subset patients with metastatic colorectal cancer (mCRC) treated with chemotherapy+/ cediranib, a vascular endothelial growth factor (VEGF) signalling inhibitor (VEGFi). Exploring biomarkers at pre- and on-treatment may identify patient subgroups showing clinical benefit on cediranib combination. METHODS: Two hundred and seven serum proteins were analysed in 588 mCRC patients at pre- and on treatment with chemotherapy (FOLFOX/CAPOX)+/-cediranib 20 mg. Patients were enrolled in the phase III trial HORIZON II. We correlated baseline biomarker signatures and pharmacodynamic (PD) biomarkers with PFS and OS. RESULTS: We identified a baseline signature (BS) of 47 biomarkers that included VEGFA, VEGFD, VEGFR2, VEGFR3 and TIE-2, which defined two distinct subgroups of patients. Patients treated with chemotherapy plus cediranib who had 'high' BS had shorter PFS (HR=1.82, P=0.003) than patients with 'low' BS. This BS did not correlate with PFS of the patients treated with chemotherapy plus placebo. In addition, we identified a profile of 16 PD proteins on treatment associated with PFS (HR=0.58, P<0.001) and OS (HR=0.52, P<0.001) in patients treated with chemotherapy plus cediranib. This PD profile did not correlate with PFS and OS in patients treated with chemotherapy plus placebo. CONCLUSIONS: Serum proteins may represent relevant biomarkers to predict the outcome of patients treated with VEGFi-based therapies. We report a BS and PD biomarkers that may identify mCRC patients showing increased benefit of combining cediranib with chemotherapy. These exploratory findings need to be validated in future prospective studies. PMID- 25121957 TI - Rapid detection of shrimp white spot syndrome virus by real time, isothermal recombinase polymerase amplification assay. AB - White spot syndrome virus (WSSV) causes large economic losses to the shrimp aquaculture industry, and thus far there are no efficient therapeutic treatments available against this lethal virus. In this study, we present the development of a novel real time isothermal recombinase polymerase amplification (RPA) assay for WSSV detection on a small ESEQuant Tube Scanner device. The RPA sensitivity, specificity and rapidity were evaluated by using a plasmid standard as well as viral and shrimp genomic DNAs. Compared with qPCR, the RPA assay revealed more satisfactory performance. It reached a detection limit up to 10 molecules in 95% of cases as determined by probit analysis of 8 independent experiments within 6.41 +/- 0.17 min at 39 degrees C. Consequently, this rapid RPA method has great application potential for field use or point of care diagnostics. PMID- 25121959 TI - Physical activity behavior and role overload in mothers. AB - We examined physical activity stages of change, physical activity behavior, and role overload in different stages of motherhood in a predominantly Australian sample. Neither physical activity behavior, stages of physical activity change, nor role overload significantly differed across motherhood groups. Role overload was significantly higher for mothers in the contemplation, planning, and action stages of physical activity than in the maintenance stage of change. Role overload had a weak, although significant, negative correlation with leisure-time physical activity. We conclude that strategies focused upon reducing role overload or perceived role overload have only limited potential to meaningfully increase leisure-time physical activity in mothers. PMID- 25121955 TI - Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. AB - BACKGROUND: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. RESULTS: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n=430) and non-aggressive (n=413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62 0.96; P-trend=0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. CONCLUSIONS: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC. PMID- 25121960 TI - The population genetics of evolutionary rescue. AB - Evolutionary rescue occurs when a population that is threatened with extinction by an environmental change adapts to the change sufficiently rapidly to survive. Here we extend the mathematical theory of evolutionary rescue. In particular, we model evolutionary rescue to a sudden environmental change when adaptation involves evolution at a single locus. We consider adaptation using either new mutations or alleles from the standing genetic variation that begin rare. We obtain several results: i) the total probability of evolutionary rescue from either new mutation or standing variation; ii) the conditions under which rescue is more likely to involve a new mutation versus an allele from the standing genetic variation; iii) a mathematical description of the U-shaped curve of total population size through time, conditional on rescue; and iv) the time until the average population size begins to rebound as well as the minimal expected population size experienced by a rescued population. Our analysis requires taking into account a subtle population-genetic effect (familiar from the theory of genetic hitchhiking) that involves "oversampling" of those lucky alleles that ultimately sweep to high frequency. Our results are relevant to conservation biology, experimental microbial evolution, and medicine (e.g., the dynamics of antibiotic resistance). PMID- 25121963 TI - Synthetic, structural, NMR and catalytic studies of phosphinic amide-phosphoryl chalcogenides (chalcogen = O, S, Se) as mixed-donor bidentate ligands in zinc chemistry. AB - ortho Substituted (diphenylphosphoryl)-, (diphenylphosphorothioyl)- and (diphenylphosphoroselenoyl)-phosphinic amides o-C6H4(P(X)Ph2)(P(O)N(i)Pr2) (X = O (20a), S (20b), Se (20c)) were synthesized by ortho directed lithiation of N,N diisopropyl-P,P-diphenylphosphinic amide (Ph2P(O)N(i)Pr2) followed by trapping with Ph2PCl and subsequent oxidation of the o-(diphenylphosphine)phosphinic amide (19) with H2O2, S8 and Se. The reaction of the new mixed-donor bidentate ligands with zinc dichloride afforded the corresponding complexes [ZnCl2(P(X)Ph2)o C6H4(P(O)N(i)Pr2)] (21a-c). The new compounds were structurally characterized in solution by nuclear magnetic resonance spectroscopy and in the solid-state by X ray diffraction analysis of the ligand (20b) and the three complexes (21a-c). The X-ray crystal structure of 20b suggests the existence of a P[double bond, length as m-dash]O->P(S)-C intramolecular nonbonded interaction. The natural bond orbital (NBO) analysis using DFT methods showed that the stabilization effect provided by a nO->sigma*P-C orbital interaction was negligible. The molecular structure of the complexes consisted of seven-membered chelates formed by O,X coordination of the ligands to the zinc cation. The metal is four-coordinated by binding to the two chlorine atoms showing a distorted tetrahedral geometry. Applications in catalysis revealed that hemilabile ligands 20a-c act as significant promoters of the addition of diethylzinc to aldehydes, with 20a showing the highest activity. Chelation of Et2Zn with 20a was evidenced by NMR spectroscopy. PMID- 25121961 TI - Awakening and withdrawal of life-sustaining treatment in cardiac arrest survivors treated with therapeutic hypothermia*. AB - OBJECTIVES: To characterize the prevalence of withdrawal of life-sustaining treatment, as well as the time to awakening, short-term neurologic outcomes, and cause of death in comatose survivors of out-of-hospital resuscitated cardiopulmonary arrests treated with therapeutic hypothermia. DESIGN: Single center, prospective observational cohort study of consecutive patients with out of-hospital cardiopulmonary arrests. SETTING: Academic tertiary care hospital and level one trauma center in Minneapolis, MN. PATIENTS: Adults with witnessed, nontraumatic, out-of-hospital cardiopulmonary arrests regardless of initial electrocardiographic rhythm with return of spontaneous circulation who were admitted to an ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study cohort included 154 comatose survivors of witnessed out-of-hospital cardiopulmonary arrests who were admitted to an ICU during the 54-month study period. One hundred eighteen patients (77%) were treated with therapeutic hypothermia. The mean age was 59 years, 104 (68%) were men, and 83 (54%) had an initial rhythm of ventricular tachycardia or fibrillation. Only eight of all 78 patients (10%) who died qualified as brain dead; and 81% of all patients (63 of 78) who died did so after withdrawal of life-sustaining treatment. Twenty of 56 comatose survivors (32%) treated with hypothermia who awoke (as defined by Glasgow Motor Score of 6) and had good neurologic outcomes (defined as Cerebral Performance Category 1-2) did so after 72 hours. CONCLUSIONS: Our study supports delaying prognostication and withdrawal of life-sustaining treatment to beyond 72 hours in cases treated with therapeutic hypothermia. Larger multicenter prospective studies are needed to better define the most appropriate time frame for prognostication in comatose cardiac arrest survivors treated with therapeutic hypothermia. These data are also consistent with the notion that a majority of out-of-hospital cardiopulmonary arrest survivors die after a decision to withdrawal of life-sustaining treatment and that very few of these survivors progress to brain death. PMID- 25121965 TI - Risk factors for cardiovascular disease in people with idiopathic pulmonary fibrosis: a population-based study. AB - OBJECTIVE: People with idiopathic pulmonary fibrosis (IPF) have been shown to be at an increased risk for cardiovascular (CV) disease, but reasons for this are unknown. The aim of this study was to compare the prevalence of common CV risk factors in people with IPF and the general population and establish the incidence of ischemic heart disease (IHD) and stroke after the diagnosis of IPF, controlling for these risk factors. METHODS: We used data from a large, UK primary care database to identify incident cases of IPF and matched general population control subjects. We compared the prevalence of risk factors for CV disease and prescription of CV medications in people with IPF (before diagnosis) with control subjects from the general population and assessed the incidence of IHD and stroke in people with IPF (after diagnosis) compared with control subjects. RESULTS: We identified 3,211 cases of IPF and 12,307 control subjects. Patients with IPF were more likely to have a record of hypertension (OR, 1.31; 95% CI, 1.19-1.44), and diabetes (OR, 1.20; 95% CI, 1.07-1.34) compared with control subjects; they were also more likely to have been prescribed several CV drugs. The rate of first-time IHD events was more than twice as high in patients than control subjects (rate ratio, 2.32; 95% CI, 1.85-2.93; P < .001), but the incidence of stroke was only marginally higher (P = .09). Rate ratios for IHD and stroke were not altered substantially after adjusting for CV risk factors. CONCLUSIONS: Several CV risk factors were more prevalent in people with IPF; however, this did not account for the increased rate of IHD in this group of patients. PMID- 25121964 TI - 3-alkoxy-pyrrolo[1,2-b]pyrazolines as selective androgen receptor modulators with ideal physicochemical properties for transdermal administration. AB - We describe the synthesis and characterization of 3-alkoxy-pyrrolo[1,2 b]pyrazolines as novel selective androgen receptor (AR) modulators that possess excellent physicochemical properties for transdermal administration. Compound 26 bound to human AR with an IC50 of 0.7 nM with great selectivity over other nuclear hormone receptors and potently activated AR in a C2C12 muscle cell reporter gene assay with an EC50 of 0.5 nM. It showed high aqueous solubility of 1.3 g/L at pH 7.4, and an in silico model as well as a customized parallel artificial membrane permeability assay indicated good skin permeation. Indeed, when measuring skin permeation through excised human skin, an excellent flux of 2 MUg/(cm(2).h) was determined without any permeation enhancers. In a 2 week Hershberger model using castrated rats, the compound showed dose-dependent effects fully restoring skeletal muscle weight at 0.3 mg/kg/day after subcutaneous administration with high selectivity over prostate stimulation. PMID- 25121962 TI - Strongyloidiasis--an insight into its global prevalence and management. AB - BACKGROUND: Strongyloides stercoralis, an intestinal parasitic nematode, infects more than 100 million people worldwide. Strongyloides are unique in their ability to exist as a free-living and autoinfective cycle. Strongyloidiasis can occur without any symptoms or as a potentially fatal hyperinfection or disseminated infection. The most common risk factors for these complications are immunosuppression caused by corticosteroids and infection with human T lymphotropic virus or human immunodeficiency virus. Even though the diagnosis of strongyloidiasis is improved by advanced instrumentation techniques in isolated and complicated cases of hyperinfection or dissemination, efficient guidelines for screening the population in epidemiological surveys are lacking. METHODOLOGY AND RESULTS: In this review, we have discussed various conventional methods for the diagnosis and management of this disease, with an emphasis on recently developed molecular and serological methods that could be implemented to establish guidelines for precise diagnosis of infection in patients and screening in epidemiological surveys. A comprehensive analysis of various cases reported worldwide from different endemic and nonendemic foci of the disease for the last 40 years was evaluated in an effort to delineate the global prevalence of this disease. We also updated the current knowledge of the various clinical spectrum of this parasitic disease, with an emphasis on newer molecular diagnostic methods, treatment, and management of cases in immunosuppressed patients. CONCLUSION: Strongyloidiasis is considered a neglected tropical disease and is probably an underdiagnosed parasitic disease due to its low parasitic load and uncertain clinical symptoms. Increased infectivity rates in many developed countries and nonendemic regions nearing those in the most prevalent endemic regions of this parasite and the increasing transmission potential to immigrants, travelers, and immunosuppressed populations are indications for initiating an integrated approach towards prompt diagnosis and control of this parasitic disease. PMID- 25121966 TI - Genome-wide association analysis of radiation resistance in Drosophila melanogaster. AB - BACKGROUND: Ionizing radiation is genotoxic to cells. Healthy tissue toxicity in patients and radiation resistance in tumors present common clinical challenges in delivering effective radiation therapies. Radiation response is a complex, polygenic trait with unknown genetic determinants. The Drosophila Genetic Reference Panel (DGRP) provides a model to investigate the genetics of natural variation for sensitivity to radiation. METHODS AND FINDINGS: Radiation response was quantified in 154 inbred DGRP lines, among which 92 radiosensitive lines and 62 radioresistant lines were classified as controls and cases, respectively. A case-control genome-wide association screen for radioresistance was performed. There are 32 single nucleotide polymorphisms (SNPs) associated with radio resistance at a nominal p<10(-5); all had modest effect sizes and were common variants with the minor allele frequency >5%. All the genes implicated by those SNP hits were novel, many without a known role in radiation resistance and some with unknown function. Variants in known DNA damage and repair genes associated with radiation response were below the significance threshold of p<10(-5) and were not present among the significant hits. No SNP met the genome-wide significance threshold (p = 1.49 * 10(-7)), indicating a necessity for a larger sample size. CONCLUSIONS: Several genes not previously associated with variation in radiation resistance were identified. These genes, especially the ones with human homologs, form the basis for exploring new pathways involved in radiation resistance in novel functional studies. An improved DGRP model with a sample size of at least 265 lines and ideally up to 793 lines is recommended for future studies of complex traits. PMID- 25121967 TI - Kinetic memory based on the enzyme-limited competition. AB - Cellular memory, which allows cells to retain information from their environment, is important for a variety of cellular functions, such as adaptation to external stimuli, cell differentiation, and synaptic plasticity. Although posttranslational modifications have received much attention as a source of cellular memory, the mechanisms directing such alterations have not been fully uncovered. It may be possible to embed memory in multiple stable states in dynamical systems governing modifications. However, several experiments on modifications of proteins suggest long-term relaxation depending on experienced external conditions, without explicit switches over multi-stable states. As an alternative to a multistability memory scheme, we propose "kinetic memory" for epigenetic cellular memory, in which memory is stored as a slow-relaxation process far from a stable fixed state. Information from previous environmental exposure is retained as the long-term maintenance of a cellular state, rather than switches over fixed states. To demonstrate this kinetic memory, we study several models in which multimeric proteins undergo catalytic modifications (e.g., phosphorylation and methylation), and find that a slow relaxation process of the modification state, logarithmic in time, appears when the concentration of a catalyst (enzyme) involved in the modification reactions is lower than that of the substrates. Sharp transitions from a normal fast-relaxation phase into this slow-relaxation phase are revealed, and explained by enzyme-limited competition among modification reactions. The slow-relaxation process is confirmed by simulations of several models of catalytic reactions of protein modifications, and it enables the memorization of external stimuli, as its time course depends crucially on the history of the stimuli. This kinetic memory provides novel insight into a broad class of cellular memory and functions. In particular, applications for long-term potentiation are discussed, including dynamic modifications of calcium-calmodulin kinase II and cAMP-response element-binding protein essential for synaptic plasticity. PMID- 25121968 TI - WW domain folding complexity revealed by infrared spectroscopy. AB - Although the intrinsic tryptophan fluorescence of proteins offers a convenient probe of protein folding, interpretation of the fluorescence spectrum is often difficult because it is sensitive to both global and local changes. Infrared (IR) spectroscopy offers a complementary measure of structural changes involved in protein folding, because it probes changes in the secondary structure of the protein backbone. Here we demonstrate the advantages of using multiple probes, infrared and fluorescence spectroscopy, to study the folding of the FBP28 WW domain. Laser-induced temperature jumps coupled with fluorescence or infrared spectroscopy have been used to probe changes in the peptide backbone on the submillisecond time scale. The relaxation dynamics of the beta-sheets and beta turn were measured independently by probing the corresponding IR bands assigned in the amide I region. Using these wavelength-dependent measurements, we observe three kinetics phases, with the fastest process corresponding to the relaxation kinetics of the turns. In contrast, fluorescence measurements of the wild-type WW domain and tryptophan mutants exhibit single-exponential kinetics with a lifetime that corresponds to the slowest phase observed by infrared spectroscopy. Mutant sequences provide evidence of an intermediate dry molten globule state. The slowest step in the folding of this WW domain is the tight packing of the side chains in the transition from the dry molten globule intermediate to the native structure. This study demonstrates that using multiple complementary probes enhances the interpretation of protein folding dynamics. PMID- 25121969 TI - iNitro-Tyr: prediction of nitrotyrosine sites in proteins with general pseudo amino acid composition. AB - Nitrotyrosine is one of the post-translational modifications (PTMs) in proteins that occurs when their tyrosine residue is nitrated. Compared with healthy people, a remarkably increased level of nitrotyrosine is detected in those suffering from rheumatoid arthritis, septic shock, and coeliac disease. Given an uncharacterized protein sequence that contains many tyrosine residues, which one of them can be nitrated and which one cannot? This is a challenging problem, not only directly related to in-depth understanding the PTM's mechanism but also to the nitrotyrosine-based drug development. Particularly, with the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop a high throughput tool in this regard. Here, a new predictor called "iNitro-Tyr" was developed by incorporating the position-specific dipeptide propensity into the general pseudo amino acid composition for discriminating the nitrotyrosine sites from non-nitrotyrosine sites in proteins. It was demonstrated via the rigorous jackknife tests that the new predictor not only can yield higher success rate but also is much more stable and less noisy. A web-server for iNitro Tyr is accessible to the public at http://app.aporc.org/iNitro-Tyr/. For the convenience of most experimental scientists, we have further provided a protocol of step-by-step guide, by which users can easily get their desired results without the need to follow the complicated mathematics that were presented in this paper just for the integrity of its development process. It has not escaped our notice that the approach presented here can be also used to deal with the other PTM sites in proteins. PMID- 25121970 TI - Efficiency of dendritic cell vaccination against B16 melanoma depends on the immunization route. AB - Dendritic cells (DC) presenting tumor antigens are crucial to induce potent T cell-mediated anti-tumor immune responses. Therefore DC-based cancer vaccines have been established for therapy, however clinical outcomes are often poor and need improvement. Using a mouse model of B16 melanoma, we found that the route of preventive DC vaccination critically determined tumor control. While repeated DC vaccination did not show an impact of the route of DC application on the prevention of tumor growth, a single DC vaccination revealed that both the imprinting of skin homing receptors and an enhanced proliferation state of effector T cells was seen only upon intracutaneous but not intravenous or intraperitoneal immunization. Tumor growth was prevented only by intracutaneous DC vaccination. Our results indicate that under suboptimal conditions the route of DC vaccination crucially determines the efficiency of tumor defense. DC-based strategies for immunotherapy of cancer should take into account the immunization route in order to optimize tissue targeting of tumor antigen specific T cells. PMID- 25121972 TI - Making mock-FNA smears from fresh surgical pathology specimens to improve smear preparation technique and to create cytohistological correlation series. AB - BACKGROUND: Fine needle aspiration (FNA) cytology is a well-established diagnostic method based on the microscopic interpretation of often scant cytological material; therefore, experience, good technique and smear quality are equally important in obtaining satisfactory results. AIMS OF STUDY: We studied the use of fresh surgical pathology specimens for making so-called mock-FNA smears with the potential of cytohistological correlation. Additionally, we studied how this process aids the improvement of preparation technique and smear quality. METHODS: Cytological aspirates from 32 fresh biopsy specimens from various sites: lung (20), lymph nodes (6), and breast (6) were obtained, all with a clinical diagnosis of tumor. Aspiration was performed from grossly palpable tumors. 25 G needle and Cameco-type syringe holder was used with minimal or no suction. RESULTS: Unfixed surgical specimens provided sufficient cytological material that resulted in good quality smears. After standard processing of specimens into microscopic sections from paraffin embedded tissues, cytohistological case-series were created. No significant alteration was reported in tissue architecture on hematoxylin-eosin stained sections after the aspiration procedure. A gradual, but steady improvement was observed in smear quality just after a few preparations. DISCUSSIONS AND CONCLUSIONS: Our study proved that surgical specimens may be used as a source of cytological material to create cytohistological correlation studies and also to improve FNA cytology skills. The use of very fine gauge needle (25 G, 0,6 mm diameter) during the sampling process does not alter tissue architecture therefore the final histopathological diagnosis is not compromised. We conclude that by using fresh surgical specimens useful cytohistological collections can be created both as a teaching resource and as improving experience. PMID- 25121973 TI - Pregnancy, maternal exposure to analgesic medicines, and leukemia in Brazilian children below 2 years of age. AB - Childhood leukemia etiology, and mainly the interactions of genetic and environmental risk factors, remains largely unexplored. This national hospital based case-control study was carried out in Brazil among children aged 0-23 months who were recruited at cancer and general hospitals in 13 states. Maternal medicine intake during pregnancy, including analgesic intake, was assessed by face-to-face interviews with the mothers of 231 leukemia patients and 411 controls. Unconditional logistic regression was used to ascertain crude and adjusted odds ratios (ORs), and their 95% confidence intervals (CIs) for the association between maternal analgesic use during pregnancy and early age leukemia. Acetaminophen use during the first trimester of pregnancy showed an OR=0.39 (95% CI 0.17-0.93) for acute lymphocytic leukemia and an OR=0.37 (95% CI 0.16-0.88) for use in the second trimester. For acute myeloid leukemia, an OR=0.11 (95% CI 0.02-0.97) was found following acetaminophen use in the second trimester. For acute lymphocytic leukemia, the exclusive use of dipyrone during preconception showed an OR=1.63 (95% CI 1.06-2.53) and dipyrone intake during lactation showed an OR=2.00 (95% CI 1.18-3.39). These results suggest that acetaminophen use during pregnancy may protect against development of early age leukemia in the offspring, whereas dipyrone use may act as a risk factor for such an outcome. PMID- 25121971 TI - Mechanical cell-matrix feedback explains pairwise and collective endothelial cell behavior in vitro. AB - In vitro cultures of endothelial cells are a widely used model system of the collective behavior of endothelial cells during vasculogenesis and angiogenesis. When seeded in an extracellular matrix, endothelial cells can form blood vessel like structures, including vascular networks and sprouts. Endothelial morphogenesis depends on a large number of chemical and mechanical factors, including the compliancy of the extracellular matrix, the available growth factors, the adhesion of cells to the extracellular matrix, cell-cell signaling, etc. Although various computational models have been proposed to explain the role of each of these biochemical and biomechanical effects, the understanding of the mechanisms underlying in vitro angiogenesis is still incomplete. Most explanations focus on predicting the whole vascular network or sprout from the underlying cell behavior, and do not check if the same model also correctly captures the intermediate scale: the pairwise cell-cell interactions or single cell responses to ECM mechanics. Here we show, using a hybrid cellular Potts and finite element computational model, that a single set of biologically plausible rules describing (a) the contractile forces that endothelial cells exert on the ECM, (b) the resulting strains in the extracellular matrix, and (c) the cellular response to the strains, suffices for reproducing the behavior of individual endothelial cells and the interactions of endothelial cell pairs in compliant matrices. With the same set of rules, the model also reproduces network formation from scattered cells, and sprouting from endothelial spheroids. Combining the present mechanical model with aspects of previously proposed mechanical and chemical models may lead to a more complete understanding of in vitro angiogenesis. PMID- 25121976 TI - Prevalence and incidence of diabetes in Stockholm County 1990-2010. AB - BACKGROUND: Diabetes is on the rise in the western world, but data from Scandinavia are inconsistent with indications of stable or even reverse trends. To shed new light on this issue, we investigated diabetes trends in Stockholm County 1990-2010, taking into account trends in risk factors and mortality. METHODS: We used data from a large population-based quadrennial public health survey conducted between 1990 and 2010 in Stockholm County (~ 2.1 million inhabitants), supplemented with data from national registers. The age standardized prevalence and incidence rates of diabetes and related risk factors 1990-2010 were estimated in adult inhabitants. We also modelled the influence of potential risk factors on the diabetes trends and estimated the life time risk of diabetes. RESULTS: The prevalence of diabetes was 4.6% (95% confidence interval (CI); 4.5-4.8%) in 2010 compared to 2.8% (95% CI; 2.3-3.5%) in 1990. Between 1990 and 2002 the prevalence rose annually by 3.8% (95% CI; 2.1-5.5). Incidence rates showed a similar pattern and rose by 3.0% (95% CI; 0.3-5.7%) annually 1990-2002. The rising incidence was mainly attributable to increasing prevalence of overweight/obesity, which rose by 46% during the observation period. In 2010, the lifetime risk of adult onset diabetes was 28% (95% CI; 26-31%) in men and 19% (95% CI; 17-21%) in women. CONCLUSIONS: Diabetes rates have been increasing in Stockholm over the last decades, both in terms of incidence and prevalence, and this development is most likely the result of increasing overweight and obesity in the population. PMID- 25121974 TI - Cardiovascular complications following chronic treatment with cocaine and testosterone in adolescent rats. AB - Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR), and exacerbated the tachycardiac baroreflex response. Cocaine treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function. PMID- 25121977 TI - Cost-utility analysis of a treatment advice to discontinue inappropriate long term antidepressant use in primary care. AB - BACKGROUND: Antidepressant prescriptions have increased exponentially, burdening health care costs. OBJECTIVE: To evaluate the costs and effects of an antidepressant cessation advice in case of inappropriate long-term use in primary care, i.e. long-term usage without a (current) indication. METHODS: A economic evaluation during 1-year follow-up was performed, from a societal perspective, as part of a cluster-randomised controlled clinical trial (PANDA). Costs were assessed using the Trimbos/iMTA questionnaire for costs associated with psychiatric illness. Health-related quality of life was measured using the EuroQol 5D. Outcome was costs per quality adjusted life year (QALY). Missing values were estimated using multiple imputation, bootstrap simulations were performed to address the uncertainty surrounding the incremental cost effectiveness ratios (ICERs). RESULTS: There was no difference in average QALYs between the intervention (0.70) and control group (0.72) [difference -0.02 (95% CI -0.05 to 0.10)]. The intervention group, however, was less expensive than the control group (total costs ?3636 versus ?5267, respectively). Most cost effectiveness pairs were located in the south-west quadrant of the cost effectiveness plane, implying the intervention was less effective but also less costly. The ICER of the pooled data was ?70,180, meaning that for one QALY lost, ?70,180 is saved. CONCLUSIONS: This study shows that an antidepressant cessation advice given to patients (and their FPs) with inappropriate long-term antidepressant usage, albeit not effective, does seem to result in a reduction of societal costs. This reduction in costs is mostly due to reduction of productivity losses, possibly due to patient empowerment and loss of stigma. PMID- 25121978 TI - Attitudes about providing HIV care: voices from publicly funded clinics in California. AB - BACKGROUND: As the enactment of health care reform becomes a reality in the USA, it has been widely predicted that HIV+ patients will increasingly be cared for by primary care physicians (PCPs), many of whom lack the experience to deliver full spectrum HIV care. OBJECTIVE: To describe PCPs' preparedness for an influx of HIV+ patients. METHODS: This qualitative study included interviews with 20 PCPs from community health centres in California. We inquired about clinicians' experiences with HIV, their strategies for dealing with unfamiliar aspects of medicine and their management of complicated patients. We also identified the clinicians' preferred types of information and consultation resources. RESULTS: PCPs are not yet comfortable as providers of comprehensive HIV care; however, they are dedicated to delivering excellent care to all of their patients, regardless of disease process. Although they prefer to refer HIV+ patients to centres of excellence, they are willing to adopt full responsibility when necessary and believe they can deliver high-quality HIV care if provided with adequate consultation and informational resources. CONCLUSIONS: The Affordable Care Act will insure an estimated 20000 more HIV+ patients in California. With a dwindling supply of HIV specialists, many of these patients will be principally cared for by PCPs. PCPs will go to great lengths to ensure that HIV+ patients receive superior care, but they need the support of HIV specialists to expand their skills. Priority should be given to ensuring that expert consultation is widely available to PCPs who find themselves caring for HIV+ patients. PMID- 25121979 TI - Population-based Stroke Atlas for outcome prediction: method and preliminary results for ischemic stroke from CT. AB - BACKGROUND AND PURPOSE: Knowledge of outcome prediction is important in stroke management. We propose a lesion size and location-driven method for stroke outcome prediction using a Population-based Stroke Atlas (PSA) linking neurological parameters with neuroimaging in population. The PSA aggregates data from previously treated patients and applies them to currently treated patients. The PSA parameter distribution in the infarct region of a treated patient enables prediction. We introduce a method for PSA calculation, quantify its performance, and use it to illustrate ischemic stroke outcome prediction of modified Rankin Scale (mRS) and Barthel Index (BI). METHODS: The preliminary PSA was constructed from 128 ischemic stroke cases calculated for 8 variants (various data aggregation schemes) and 3 case selection variables (infarct volume, NIHSS at admission, and NIHSS at day 7), each in 4 ranges. Outcome prediction for 9 parameters (mRS at 7th, and mRS and BI at 30th, 90th, 180th, 360th day) was studied using a leave-one-out approach, requiring 589,824 PSA maps to be analyzed. RESULTS: Outcomes predicted for different PSA variants are statistically equivalent, so the simplest and most efficient variant aiming at parameter averaging is employed. This variant allows the PSA to be pre-calculated before prediction. The PSA constrained by infarct volume and NIHSS reduces the average prediction error (absolute difference between the predicted and actual values) by a fraction of 0.796; the use of 3 patient-specific variables further lowers it by 0.538. The PSA-based prediction error for mild and severe outcomes (mRS = [2]-[5]) is (0.5-0.7). Prediction takes about 8 seconds. CONCLUSIONS: PSA-based prediction of individual and group mRS and BI scores over time is feasible, fast and simple, but its clinical usefulness requires further studies. The case selection operation improves PSA predictability. A multiplicity of PSAs can be computed independently for different datasets at various centers and easily merged, which enables building powerful PSAs over the community. PMID- 25121980 TI - Emptying effect of massage on parotid gland radioiodine content. AB - BACKGROUND: To prevent salivary dysfunction in thyroid cancer patients who have undergone radioiodine ablation, massaging the parotid gland (PG) is presumed to be helpful for the removal of radioiodine. The purpose of this study was to evaluate the effect of PG massage in the removal of radioiodine from the PG. METHODS: Forty-four patients (female, 38; 49.1 +/- 11.0 years) who underwent total thyroidectomy followed by I-131 ablation were included in this prospective study. Three serial salivary gland scans were performed 2 h after administration of I-123 in thyroid hormone withdrawal status. The patients were divided into two groups. There was a 1-min (or 2-min) interval between the first and second scans for control, followed by the performance of PG massage for 1 min (or 2 min) between the second and third scans. Changes in uptakes were calculated between the first and second scans (control) and between the second and third scans (massage). RESULTS: The mean change in uptake at the 1-min massage was 0.97 +/- 11.27%, whereas that at the 1-min control was 11.54 +/- 5.59% (P<0.001). The mean change in uptake at the 2-min massage was also significantly lower than that at the 2-min control (11.11 +/- 6.97 vs. -0.85 +/- 9.78%, P<0.001). However, no statistical difference was observed between the mean changes in uptake after 1- and 2-min massages (P=0.573). CONCLUSION: PG massage reduced the radioiodine uptake in the PG, and the effect of PG massage for 1 min was comparable with that of PG massage for 2 min. PG massage can be applied to thyroid cancer patients who receive radioiodine therapy to reduce PG dysfunction. PMID- 25121981 TI - Who Seeks Cita Con El Doctor? Twelve Years of Spanish-Language Radio Program Targeting U.S. Latinos. AB - PURPOSE: Spanish-dominant Latinos make up 13% of the U.S. population, and this group is poorer and faces multiple threats to health compared with the general population. Additionally, Spanish speakers face challenges accessing health information that is often not available in Spanish. This study provides a descriptive epidemiology of a unique, low-cost health information source: the longest-running U.S.-based Spanish-language call-in radio health education program. METHOD: From the universe of all calls 1999 to 2011, stratified random sampling yielded 1,237 analyzed calls, which were manually coded for caller sex, age, proxy status, and health concern. Descriptive statistics were used to examine basic demographics of callers and call topics overall and by sex and proxy caller status. RESULTS: Among all calls, the top three call-generating health topics were specific symptoms/conditions, sexual/reproductive health, and gastrointestinal concerns. The top nine topics were consistent among women, men, and proxy callers; however, relative frequency of topics varied across groups. Nearly one quarter of calls were initiated on behalf of someone, generally a child, spouse or sibling, or parent. Sixty percent of callers were women; women made 70% of proxy calls. CONCLUSION: Understanding the differences in information seeking behaviors, information needs, and source preferences is important for determining where and how to disseminate health information and may help explain disparities in knowledge and health outcomes. The radio talk show format provides a uniquely personal, culturally sensitive channel for meeting health information needs of a vulnerable population while leveraging the cost-effectiveness and wide reach of a mass medium. PMID- 25121982 TI - Application of a socio-ecological model to mother-infant bed-sharing. AB - Mother-infant bed-sharing has been associated with an increased risk of sleep related infant deaths, and thus, health messaging has aimed to discourage this behavior. Despite this messaging, bed-sharing remains a common practice in the United States, especially among minority families. Moreover, rates of accidental suffocation and strangulation in bed (often related to bed-sharing) are on the rise, with Black infants at two to three times greater risk than Whites. Multiple studies have identified risk factors for bed-sharing, but a gap remains between findings and translation into interventions. The socio-ecological model (SEM) has been suggested as a way to study and design interventions addressing complex public health issues. This article reconceptualizes the literature on mother infant bed-sharing using the SEM. PubMed, POPLINE, ERIC, and Psych Info were searched for articles that (a) included bed-sharing as the outcome variable, (b) were published between 2000 and 2013, (c) were conducted in the United States, and (d) included quantitative comparison of more than one factor. The following data were extracted: sample characteristics, bed-sharing definition, methods, factors examined, key findings, and conclusions. Data were summarized into five SEM levels--infant, maternal, family and household, and community and society, nested within the historical context of race. Sixteen studies met inclusion criteria. Significant factors associated with bed-sharing were present within each SEM level of influence. Educational interventions may increase efficacy by attending to multiple levels of the SEM, especially when implementing such interventions within minority subpopulations. Using a harm reduction approach to reducing the risk around bed-sharing may be one way to account for the multiple influences on bed-sharing. The science and practice of minimizing mother-infant bed-sharing may be advanced through use of the SEM. PMID- 25121985 TI - Candida albicans pathogenicity and epithelial immunity. PMID- 25121984 TI - Lipoprotein-apheresis reduces circulating microparticles in individuals with familial hypercholesterolemia. AB - Lipoprotein-apheresis (apheresis) removes LDL-cholesterol in patients with severe dyslipidemia. However, reduction is transient, indicating that the long-term cardiovascular benefits of apheresis may not solely be due to LDL removal. Microparticles (MPs) are submicron vesicles released from the plasma membrane of cells. MPs, particularly platelet-derived MPs, are increasingly being linked to the pathogenesis of many diseases. We aimed to characterize the effect of apheresis on MP size, concentration, cellular origin, and fatty acid concentration in individuals with familial hypercholesterolemia (FH). Plasma and MP samples were collected from 12 individuals with FH undergoing routine apheresis. Tunable resistive pulse sensing (np200) and nanoparticle tracking analysis measured a fall in MP concentration (33 and 15%, respectively; P < 0.05) pre- to post-apheresis. Flow cytometry showed MPs were predominantly annexin V positive and of platelet (CD41) origin both pre- (88.9%) and post-apheresis (88.4%). Fatty acid composition of MPs differed from that of plasma, though apheresis affected a similar profile of fatty acids in both compartments, as measured by GC-flame ionization detection. MP concentration was also shown to positively correlate with thrombin generation potential. In conclusion, we show apheresis nonselectively removes annexin V-positive platelet-derived MPs in individuals with FH. These MPs are potent inducers of coagulation and are elevated in CVD; this reduction in pathological MPs could relate to the long-term benefits of apheresis. PMID- 25121986 TI - Efficacy of an internet-based problem-solving training for teachers: results of a randomized controlled trial. AB - OBJECTIVE: The primary purpose of this randomized controlled trial (RCT) was to evaluate the efficacy of internet-based problem-solving training (iPST) for employees in the educational sector (teachers) with depressive symptoms. The results of training were compared to those of a waitlist control group (WLC). METHODS: One-hundred and fifty teachers with elevated depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D >=16) were assigned to either the iPST or WLC group. The iPST consisted of five lessons, including problem solving and rumination techniques. Symptoms were assessed before the intervention began and in follow-up assessments after seven weeks, three months, and six months. The primary outcome was depressive symptom severity (CES-D). Secondary outcomes included general and work-specific self-efficacy, perceived stress, pathological worries, burnout symptoms, general physical and mental health, and absenteeism. RESULTS: iPST participants displayed a significantly greater reduction in depressive symptoms after the intervention (d=0.59, 95% CI 0.26 0.92), after three months (d=0.37, 95% CI 0.05-0.70) and after six months (d=0.38, 95% CI 0.05-0.70) compared to the control group. The iPST participants also displayed significantly higher improvements in secondary outcomes. However, workplace absenteeism was not significantly affected. CONCLUSION: iPST is effective in reducing symptoms of depression among teachers. Disseminated on a large scale, iPST could contribute to reducing the burden of stress-related mental health problems among teachers. Future studies should evaluate iPST approaches for use in other working populations. PMID- 25121983 TI - Epoxy alcohol synthase of the rice blast fungus represents a novel subfamily of dioxygenase-cytochrome P450 fusion enzymes. AB - The genome of the rice blast fungus Magnaporthe oryzae codes for two proteins with N-terminal dioxygenase (DOX) and C-terminal cytochrome P450 (CYP) domains, respectively. One of them, MGG_13239, was confirmed as 7,8-linoleate diol synthase by prokaryotic expression. The other recombinant protein (MGG_10859) possessed prominent 10R-DOX and epoxy alcohol synthase (EAS) activities. This enzyme, 10R-DOX-EAS, transformed 18:2n-6 sequentially to 10(R)-hydroperoxy 8(E),12(Z)-octadecadienoic acid (10R-HPODE) and to 12S(13R)-epoxy-10(R)-hydroxy 8(E)-octadecenoic acid as the end product. Oxygenation at C-10 occurred by retention of the pro-R hydrogen of C-8 of 18:2n-6, suggesting antarafacial hydrogen abstraction and oxygenation. Experiments with (18)O2 and (16)O2 gas confirmed that the epoxy alcohol was formed from 10R-HPODE, likely by heterolytic cleavage of the dioxygen bond with formation of P450 compound I, and subsequent intramolecular epoxidation of the 12(Z) double bond. Site-directed mutagenesis demonstrated that the cysteinyl heme ligand of the P450 domain was required for the EAS activity. Replacement of Asn(965) with Val in the conserved AsnGlnXaaGln sequence revealed that Asn(965) supported formation of the epoxy alcohol. 10R-DOX EAS is the first member of a novel subfamily of DOX-CYP fusion proteins of devastating plant pathogens. PMID- 25121988 TI - Personal Out-of-Pocket Health Expenses, United States, 1970. AB - Money spent on medical and dental care is an important concern of many families. To alleviate the burden, a large number of families carry health insurance to cover much of this expense. However, there remain some direct out-of- pocket health expenditures for many of us. During 1971 the Health Interview Survey conducted a study to measure the out-of-pocket health expenses of the civilian population not confined to institutions. A self-enumeration questionnaire was mailed to some 11,970 households comprising a representative sample of the Nation's households, the same sample as that used in the last quarter of 1970 for the Health Interview Survey (see the "Source of Data" for details). Information was requested on out-of-pocket expenditures in 1970 for hospital, doctor, dental, or optical services, prescribed medicine, and other medical expenses for each family member as well as the total amount of health insurance premiums (including Medicare premiums) paid directly by the family during 1970. No attempt has been made in the study to measure the total cost of medical and dental care, since it is difficult, if not impossible, for family members to report the amounts paid through insurance benefits, government programs such as Medicare and Medicaid, welfare, philanthropy, and other third-party payers. The total amount of national health expenditures, including out-of-pocket costs, is measured by the Social Security Administration and reported in the Social Security Bulletin in several annual series of reports. Another source of expenditure data is the Center for Health Administration Studies of the University of Chicago. PMID- 25121987 TI - Induced pluripotent stem cells without c-Myc ameliorate retinal oxidative damage via paracrine effects and reduced oxidative stress in rats. AB - PURPOSE: To investigate the efficacy and mechanisms of non-c-Myc induced pluripotent stem cell (iPSC) transplantation in a rat model of retinal oxidative damage. METHODS: Paraquat was intravitreously injected into Sprague-Dawley rats. After non-c-Myc iPSC transplantation, retinal function was evaluated by electroretinograms (ERGs). The generation of reactive oxygen species (ROS) was determined by lucigenin- and luminol-enhanced chemiluminescence. The expression of brain-derived neurotrophic factor, ciliary neurotrophic factor, basic fibroblast growth factor (bFGF), stromal cell-derived factor (SDF)-1alpha, and CXCR4 was measured by immunohistochemistry and ELISA. An in vitro study using SH SY5Y cells was performed to verify the protective effects of SDF-1alpha. RESULTS: Transplantation of non-c-Myc iPSCs effectively promoted the recovery of the b wave ratio in ERGs and significantly ameliorated retinal damage. Non-c-Myc iPSC transplantation decreased ROS production and increased the activities of superoxide dismutase and catalase, thereby reducing retinal oxidative damage and apoptotic cells. Moreover, non-c-Myc iPSC transplantation resulted in significant upregulation of SDF-1alpha, followed by bFGF, accompanied by a significant improvement in the ERG. In vitro studies confirmed that treatment with SDF-1alpha significantly reduced apoptosis in a dose-dependent manner in SH-SY5Y cells. Most transplanted cells remained in the subretinal space, with spare cells expressing neurofilament M markers at day 28. Six months after transplantation, no tumor formation was seen in animals with non-c-Myc iPSC grafts. CONCLUSIONS: We demonstrated the potential benefits of non-c-Myc iPSC transplantation for treating oxidative-damage-induced retinal diseases. SDF-1alpha and bFGF play important roles in facilitating the amelioration of retinal oxidative damage after non-c-Myc iPSC transplantation. PMID- 25121990 TI - Antibiotic resistance: a primer and call to action. AB - During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention, 2013; World Health Organization, 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral, and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices. PMID- 25121989 TI - Mucin 5B promoter polymorphism is associated with susceptibility to interstitial lung diseases in Chinese males. AB - The variation of G>T in the MUC5B promoter (rs35705950) has been associated with idiopathic pulmonary fibrosis (IPF) and familial interstitial pneumonia (FIP) in Caucasians, but no information is available regarding this variant in the Chinese population. We recruited 405 patients with interstitial lung diseases (ILD), including 165 IPF patients and 2043 healthy controls, for genotyping the MUC5B gene in the Chinese population. One hundred three patients with pneumonia and 360 patients with autoimmune diseases (ADs) were recruited as disease controls. Our results indicated that the prevalence of the minor allele (T) of the polymorphism rs35705950 in healthy Chinese subjects was approximately 0.66%, which was lower than that described in the Caucasian population. The frequencies of the T allele were 3.33% and 2.22% in IPF and ILD patients, respectively, and these values were significantly higher than those of healthy controls (P = 0.001, OR = 4.332 for IPF, and P = 0.002, OR = 2.855 for ILD). A stratified analysis showed that this variant in MUC5B associated with the risk for ILD mainly in older male Chinese subjects. No difference was observed between patients with pneumonia, AD patients, and healthy controls. PMID- 25121992 TI - Methylphenidate intoxication: somnolence as an uncommon clinical symptom and proof of overdosing by increased serum levels of ritalinic acid. AB - There is considerable evidence for an increase of methylphenidate (MPH) abuse; thus, physicians might be confronted more frequently with MPH intoxications. Possible symptoms of intoxications with MPH are orofacial, stereotypic movements and tics as well as tachycardia, cardiac arrhythmias, arterial hypertension, hyperthermia, hallucinations and epileptic seizures. Here we report a patient who demonstrated somnolence as an uncommon clinical feature of MPH intoxication. The patient exhibited subnormal MPH serum levels (3 MUg/l), however markedly increased serum levels of ritalinic acid (821 MUg/l; inactive metabolite of MPH), that finally confirmed the initially suspected MPH intoxication. Due to the short half-life of orally administered MPH (t1/2~3 h) the sole measurement of MPH serum levels might be misleading concerning the proof of MPH overdosing in some cases. Parallel measurement of MPH and ritalinic acid is recommended in cases with suspected MPH intoxication and insufficient anamnestic data. PMID- 25121991 TI - Cost-effectiveness of collaborative care for depression in UK primary care: economic evaluation of a randomised controlled trial (CADET). AB - BACKGROUND: Collaborative care is an effective treatment for the management of depression but evidence on its cost-effectiveness in the UK is lacking. AIMS: To assess the cost-effectiveness of collaborative care in a UK primary care setting. METHODS: An economic evaluation alongside a multi-centre cluster randomised controlled trial comparing collaborative care with usual primary care for adults with depression (n = 581). Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER) were calculated over a 12-month follow-up, from the perspective of the UK National Health Service and Personal Social Services (i.e. Third Party Payer). Sensitivity analyses are reported, and uncertainty is presented using the cost-effectiveness acceptability curve (CEAC) and the cost-effectiveness plane. RESULTS: The collaborative care intervention had a mean cost of L272.50 per participant. Health and social care service use, excluding collaborative care, indicated a similar profile of resource use between collaborative care and usual care participants. Collaborative care offered a mean incremental gain of 0.02 (95% CI: -0.02, 0.06) quality-adjusted life-years over 12 months, at a mean incremental cost of L270.72 (95% CI: -202.98, 886.04), and resulted in an estimated mean cost per QALY of L14,248. Where costs associated with informal care are considered in sensitivity analyses collaborative care is expected to be less costly and more effective, thereby dominating treatment as usual. CONCLUSION: Collaborative care offers health gains at a relatively low cost, and is cost-effective compared with usual care against a decision-maker willingness to pay threshold of L20,000 per QALY gained. Results here support the commissioning of collaborative care in a UK primary care setting. PMID- 25121994 TI - Non-glutamatergic clozapine augmentation strategies: a review and meta-analysis. AB - Persistent negative symptoms and cognitive impairment are major clinical problems in the treatment of schizophrenia. There is no convincing evidence regarding the efficacy of augmentation of clozapine with a second antipsychotic, ethyl eicosapentaenoic acid (E-EPA), an antidepressant, a mood stabilizer or extract of Ginkgo biloba in clozapine-resistant schizophrenia. We present an overview of studies in which the potential clinical utility of the addition of non glutamatergic agents to clozapine is assessed. We performed a meta-analysis on the efficacy of both risperidone and aripiprazole compared to placebo. We compared the effects of the addition of a second antipsychotic or an antidepressant to clozapine on positive, negative, overall and affective symptoms of schizophrenia in double-blind placebo-controlled trials. PMID- 25121993 TI - Pegylated interferon pharmacokinetics and self-reported depressive symptoms during antiviral treatment for chronic hepatitis C. AB - BACKGROUND: Pegylated interferon-2a (PegIFN-2a)+ribavirin treatment for chronic hepatitis C is often associated with depressive symptoms. Previous studies have failed to explore whether PegIFN-2a pharmacokinetic variability plays an etiologic role in PegIFN-2a-induced mood disorders. The objective of this investigation was to evaluate the association between trough PegIFN-2a concentration at treatment week 4 ("PegIFN-2a Cmin4") and an increase in depressive symptoms. METHODS: Using data from Virahep-C, the association between PegIFN-2a Cmin4 and the following depression outcomes were evaluated using the Center for Epidemiological Studies-Depression scale (CES-D): (1) change in CES-D score from baseline to week 12; (2) greatest difference in CES-D score between baseline and weeks 4, 12, or 24; and (3) occurrence of severe depressive symptoms (CES-D greater than 23) at weeks 4, 12, or 24. One post-hoc analysis examined whether PegIFN-2a exposure during the first week of treatment was associated with change in CES-D score from baseline to week 4. RESULTS: No significant associations between PegIFN-2a Cmin4 and the depression outcomes were observed (p>0.05). Exploratory analyses suggest a possible relationship between PegIFN-2a exposure during the first week of therapy and CES-D score change from baseline to week 4 (p=0.03). CONCLUSIONS: PegIFN-2a concentration levels from baseline to week 4 do not predict the onset and severity of depressive symptoms during 24 weeks of antiviral therapy; however PegIFN-2a levels during the first week of treatment may predict depressive symptoms in the first 4 weeks, earlier than anticipated and warrants further exploration. PMID- 25121997 TI - Palladium-catalyzed direct ortho-nitration of azoarenes using NO2 as nitro source. AB - A palladium-catalyzed direct ortho-nitration reaction of azoarenes was developed in which NO2 was used as both nitro source and oxidant for the first time. The nitration products were converted into o-aminoazoarenes or benzotriazole derivatives by a simple reduction. PMID- 25121998 TI - When meaning is useless. AB - The aim of this study is to disentangle the relative contribution of semantic and phonological representation in immediate serial recall. Indeed, short-term memory (STM) performance could be enhanced by familiarity with the phonological form of the word only or together with semantic information. Participants learned two sets of words in an unknown language: for one set they acquired both phonology and semantics, while for the other only phonology. After that, they performed two immediate serial recall tasks involving either "phonology and semantics" or "only phonology" words and one with untrained words. The analyses showed that the trained lists did not differ from each other, while they did from the untrained one. These data confirm that familiarity with the phonological form is sufficient for immediate serial recall. Therefore, we argue that semantics is not required for verbal STM, but knowledge of the phonological form is what matters. PMID- 25121995 TI - The influence of body mass index, age and sex on inflammatory disease risk in semi-captive Chimpanzees. AB - Obesity and ageing are emerging issues in the management of captive primates, including Chimpanzees, Pan troglodytes. Studies on humans show that obesity and old age can independently increase the risk of inflammatory-associated diseases indicated by elevated levels of pro-inflammatory cells and proteins in the blood of older or obese compared to levels in younger or non-obese individuals. In humans, sex can influence the outcomes of these risks. Health management of these problems in chimpanzee populations requires an understanding of similarities and differences of factors influencing inflammatory disease risks in humans and in chimpanzees. We examined the relationship between age, sex and Body Mass Index (BMI) with hematological biomarkers of inflammatory disease risk established for humans which include the neutrophil to lymphocyte ratio (NLR), and neutrophil, white blood cell (WBC), platelet microparticle and platelet counts. We found that higher values of NLR, neutrophil count and platelet microparticle count were associated with higher BMI values and older age indicating increased inflammation risk in these groups; a similar pattern to humans. There was a strong sex by age interaction on inflammation risk, with older males more at risk than older females. In contrast to human studies, total WBC count was not influenced by BMI, but like humans, WBC and platelet counts were lower in older individuals compared to younger individuals. Our findings are similar to those of humans and suggest that further insight on managing chimpanzees can be gained from extensive studies of ageing and obesity in humans. We suggest that managing BMI should be an integral part of health management in captive chimpanzee populations in order to partially reduce the risk of diseases associated with inflammation. These results also highlight parallels in inflammation risk between humans and chimpanzees and have implications for understanding the evolution of inflammation related diseases in apes. PMID- 25121996 TI - Repair-related activation of hedgehog signaling in stromal cells promotes intrahepatic hypothyroidism. AB - Thyroid hormone (TH) is important for tissue repair because it regulates cellular differentiation. Intrahepatic TH activity is controlled by both serum TH levels and hepatic deiodinases. TH substrate (T4) is converted into active hormone (T3) by deiodinase 1 (D1) but into inactive hormone (rT3) by deiodinase 3 (D3). Although the relative expressions of D1 and D3 are known to change during liver injury, the cell types and signaling mechanisms involved are unclear. We evaluated the hypothesis that changes in hepatic deiodinases result from repair related activation of the Hedgehog pathway in stromal cells. We localized deiodinase expression, assessed changes during injury, and determined how targeted manipulation of Hedgehog signaling in stromal cells impacted hepatic deiodinase expression, TH content, and TH action in rodents. Humans with chronic liver disease were also studied. In healthy liver, hepatocytes strongly expressed D1 and stromal cells weakly expressed D3. During injury, hepatocyte expression of D1 decreased, whereas stromal expression of D3 increased, particularly in myofibroblasts. Conditionally disrupting Hedgehog signaling in myofibroblasts normalized deiodinase expression. Repair-related changes in deiodinases were accompanied by reduced hepatic TH content and TH-regulated gene expression. In patients, this was reflected by increased serum rT3. Moreover, the decreases in the free T3 to rT3 and free T4 to rT3 ratios distinguished advanced from mild fibrosis, even in individuals with similar serum levels of TSH and free T4. In conclusion, the Hedgehog-dependent changes in liver stromal cells drive repair related changes in hepatic deiodinase expression that promote intrahepatic hypothyroidism, thereby limiting exposure to T3, an important factor for cellular differentiation. PMID- 25121999 TI - 20 years of leptin: leptin at 20: an overview. AB - Historically, adipose tissue was considered to be a passive storage vessel discharging nutrients in times of famine and accumulating fat in times of surfeit. This view changed with the identification of leptin as an adipocyte hormone. Leptin functions as an afferent signal in a negative feedback loop that regulates food intake and metabolism to maintain homeostatic control of adipose tissue mass. Before this, the existence of a system maintaining homeostatic control of energy balance was unclear. The identification of leptin has thus uncovered a new endocrine system that also links changes in nutrition to adaptive responses in most if not all other physiologic systems. Further studies have revealed a set of clinical syndromes caused by leptin deficiency, including lipodystrophy and hypothalamic amenorrhea. This work has led to new therapeutic approaches for a number of human conditions and has also established a conceptual framework for studying the pathogenesis of obesity. PMID- 25122001 TI - The role of dipeptidyl peptidase 4 (DPP4) in the preservation of renal function: DPP4 involvement in hemoglobin expression. AB - In a previous study, we demonstrated that dipeptidyl peptidase 4 (DPP4)-deficient rats were susceptible to reduced glomerular filtration rate as a result of streptozotocin (STZ)-induced diabetes. Therefore, we proposed that DPP4 might be responsible for the preservation of renal function. In this study, to verify the role of DPP4 in the preservation of renal function, we performed a microarray analysis of the kidneys of WT and DPP4-deficient rats after STZ treatment, and gene expression analysis using rat kidneys, human embryonic kidney 293 (HEK293) cells, and human renal cancer cells (CakI-1). The microarray analysis indicated that the expression levels of the transporter activity, heme-binding, and pheromone binding-related genes changed significantly. The results of gene expression analysis indicated that there were no significant differences in the expression levels of hemoglobin mRNA between the DPP4-deficient and WT rats; however, the expression levels of hemoglobin mRNA in the kidneys of DPP4 deficient rats tended to decrease when compared with those of both the non-STZ treated and STZ-treated WT rats. The expression levels of hemoglobin in HEK293 and Caki-1 cells were significantly decreased when DPP4 was knocked down by siRNA, were significantly increased by the addition of soluble human DPP4, and were also significantly increased by the addition of the DPP4 inhibitor, sitagliptin. The expression level of DPP4 was also significantly increased by the addition of sitagliptin in both cell types. Our findings indicate that DPP4 regulates the expression of the hemoglobin genes, and might play a role in the preservation of renal function; however, the underlying mechanism of this preservation remains to be elucidated. PMID- 25122000 TI - Gastrin induces ductal cell dedifferentiation and beta-cell neogenesis after 90% pancreatectomy. AB - Induction of beta-cell mass regeneration is a potentially curative treatment for diabetes. We have recently found that long-term gastrin treatment results in improved metabolic control and beta-cell mass expansion in 95% pancreatectomised (Px) rats. In this study, we investigated the underlying mechanisms of gastrin induced beta-cell mass expansion after Px. After 90%-Px, rats were treated with gastrin (Px+G) or vehicle (Px+V), pancreatic remnants were harvested on days 1, 3, 5, 7, and 14 and used for gene expression, protein immunolocalisation and morphometric analyses. Gastrin- and vehicle-treated Px rats showed similar blood glucose levels throughout the study. Initially, after Px, focal areas of regeneration, showing mesenchymal cells surrounding ductal structures that expressed the cholecystokinin B receptor, were identified. These focal areas of regeneration were similar in size and cell composition in the Px+G and Px+V groups. However, in the Px+G group, the ductal structures showed lower levels of keratin 20 and beta-catenin (indicative of duct dedifferentiation) and higher levels of expression of neurogenin 3 and NKX6-1 (indicative of endocrine progenitor phenotype), as compared with Px+V rats. In Px+G rats, beta-cell mass and the number of scattered beta-cells were significantly increased compared with Px+V rats, whereas beta-cell replication and apoptosis were similar in the two groups. These results indicate that gastrin treatment-enhanced dedifferentiation and reprogramming of regenerative ductal cells in Px rats, increased beta-cell neogenesis and fostered beta-cell mass expansion. PMID- 25122002 TI - UCP1 is present in porcine adipose tissue and is responsive to postnatal leptin. AB - Intrauterine growth restriction (IUGR) may be accompanied by inadequate thermoregulation, especially in piglets that are not considered to possess any brown adipose tissue (BAT) and are thus entirely dependent on shivering thermogenesis in order to maintain body temperature after birth. Leptin can stimulate heat production by promoting non-shivering thermogenesis in BAT, but whether this response occurs in piglets is unknown. Newborn female piglets that were characterised as showing IUGR (mean birth weight of approximately 0.98 kg) were therefore administered injections of either saline or leptin once a day for the first 5 days of neonatal life. The dose of leptin was 0.5 mg/kg, which is sufficient to increase plasma leptin by approximately tenfold and on the day of birth induced a rapid increase in body temperature to values similar to those of normal-sized 'control' piglets (mean birth weight of ~1.47 kg). Perirenal adipose tissue was then sampled from all offspring at 21 days of age and the presence of the BAT-specific uncoupling protein 1 (UCP1) was determined by immunohistochemistry and immunoblotting. UCP1 was clearly detectable in all samples analysed and its abundance was significantly reduced in the IUGR piglets that had received saline compared with controls, but was raised to the same amount as in controls in those IUGR females given leptin. There were no differences in gene expression between primary markers of brown and white adipose tissues between groups. In conclusion, piglets possess BAT that when stimulated exogenously by leptin can promote increased body temperature. PMID- 25122003 TI - Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat skeletal muscle. AB - Insulin resistance (IR) in skeletal muscle is an important component of both type 2 diabetes and the syndrome of sarcopaenic obesity, for which there are no effective therapies. Urocortins (UCNs) are not only well established as neuropeptides but also have their roles in metabolism in peripheral tissues. We have shown recently that global overexpression of UCN3 resulted in muscular hypertrophy and resistance to the adverse metabolic effects of a high-fat diet. Herein, we aimed to establish whether short-term local UCN3 expression could enhance glucose disposal and insulin signalling in skeletal muscle. UCN3 was found to be expressed in right tibialis cranialis and extensor digitorum longus muscles of rats by in vivo electrotransfer and the effects studied vs the contralateral muscles after 1 week. No increase in muscle mass was detected, but test muscles showed 19% larger muscle fibre diameter (P=0.030), associated with increased IGF1 and IGF1 receptor mRNA and increased SER256 phosphorylation of forkhead transcription factor. Glucose clearance into the test muscles after an intraperitoneal glucose load was increased by 23% (P=0.018) per unit mass, associated with increased GLUT1 (34% increase; P=0.026) and GLUT4 (48% increase; P=0.0009) proteins, and significantly increased phosphorylation of insulin receptor substrate-1, AKT, AKT substrate of 160 kDa, glycogen synthase kinase 3beta, AMP-activated protein kinase and its substrate acetyl coA carboxylase. Thus, UCN3 expression enhances glucose disposal and signalling in muscle by an autocrine/paracrine mechanism that is separate from its pro-hypertrophic effects, implying that such a manipulation may have promised for the treatment of IR syndromes including sarcopaenic obesity. PMID- 25122004 TI - Hepatitis B virus subgenotype A1: evolutionary relationships between Brazilian, African and Asian isolates. AB - Brazil is a country of low hepatitis B virus (HBV) endemicity in which the genotype A of HBV (HBV/A) is the most prevalent. The complete nucleotide sequences of 26 HBV/A isolates, originating from eight Brazilian states, were determined. All were adw2. Twenty-three belonged to subgenotype A1 and three to A2. By phylogenetic analysis, it was shown that all the 23 HBV/A1 isolates clustered together with isolates from Bangladesh, India, Japan, Nepal, the Philippines and United Arab Emirates, but not with those of Congo, Kenya, Malawi, Rwanda, South Africa, Tanzania, Uganda and Zimbabwe. Four amino acid residues in the polymerase (His138 in the terminal protein domain, Pro18 and His90 in the spacer, and Ser109 in the reverse transcriptase), and one (Phe17) in the precore region, predominated in Latin American and Asian HBV/A1 isolates, but were rarely encountered in African isolates, with the exception of those from Somalia. Specific variations of two adjacent amino acids in the C-terminal domain of the HBx protein, namely Ala146 and Pro147, were found in all the Brazilian, but rarely in the other HBV/A1 isolates. By Bayesian analysis, the existence of an 'Asian-American' clade within subgenotype A1 was supported by a posterior probability value of 0.996. The close relatedness of the Brazilian, Asian and Somalian isolates suggests that the HBV/A1 strains predominant in Brazil did not originate from the five million slaves who were imported from Central and Western Africa from 1551 to 1840, but rather from the 300-400,000 captives forcibly removed from southeast Africa at the middle of the 19th century. PMID- 25122006 TI - The meaningful use of electronic health records and health care quality. AB - The federal government is investing approximately $30 billion in incentives for adoption and meaningful use (MU) of electronic health records (EHRs). Whether achieving MU improves quality of care is unclear. The researchers conducted a longitudinal study of 514 primary care physicians in New York State from 2010 to 2011. Quality of care provided by those who achieved stage 1 MU was compared with the quality provided by those who used EHRs but did not achieve stage 1 MU. Generalized estimating equations were used to determine whether receipt of MU incentives was independently associated with performance on 9 MU quality measures. In 2011, 44% of physicians achieved MU and 56% did not. No difference in quality was found between those who achieved stage 1 MU and those who were using EHRs but had not achieved MU. Longer follow-up is needed to observe the full effects of this multistage national policy. PMID- 25122005 TI - Role of vascular smooth muscle PPARgamma in regulating AT1 receptor signaling and angiotensin II-dependent hypertension. AB - Peroxisome proliferator activated receptor gamma (PPARgamma) has been reported to play a protective role in the vasculature; however, the underlying mechanisms involved are not entirely known. We previously showed that vascular smooth muscle specific overexpression of a dominant negative human PPARgamma mutation in mice (S-P467L) leads to enhanced myogenic tone and increased angiotensin-II-dependent vasoconstriction. S-P467L mice also exhibit increased arterial blood pressure. Here we tested the hypotheses that a) mesenteric smooth muscle cells isolated from S-P467L mice exhibit enhanced angiotensin-II AT1 receptor signaling, and b) the increased arterial pressure of S-P467L mice is angiotensin-II AT1 receptor dependent. Phosphorylation of mitogen-activated protein/extracellular signal regulated kinase (ERK1/2) was robustly increased in mesenteric artery smooth muscle cell cultures from S-P467L in response to angiotensin-II. The increase in ERK1/2 activation by angiotensin-II was blocked by losartan, a blocker of AT1 receptors. Angiotensin-II-induced ERK1/2 activation was also blocked by Tempol, a scavenger of reactive oxygen species, and correlated with increased Nox4 protein expression. To investigate whether endogenous renin-angiotensin system activity contributes to the elevated arterial pressure in S-P467L, non-transgenic and S P467L mice were treated with the AT1 receptor blocker, losartan (30 mg/kg per day), for 14-days and arterial pressure was assessed by radiotelemetry. At baseline S-P467L mice showed a significant increase of systolic arterial pressure (142.0 +/- 10.2 vs 129.1 +/- 3.0 mmHg, p<0.05). Treatment with losartan lowered systolic arterial pressure in S-P467L (132.2 +/- 6.9 mmHg) to a level similar to untreated non-transgenic mice. Losartan also lowered arterial pressure in non transgenic (113.0 +/- 3.9 mmHg) mice, such that there was no difference in the losartan-induced depressor response between groups (-13.53 +/- 1.39 in S-P467L vs -16.16 +/- 3.14 mmHg in non-transgenic). Our results suggest that interference with PPARgamma in smooth muscle: a) causes enhanced angiotensin-II AT1 receptor mediated ERK1/2 activation in resistance vessels, b) and may elevate arterial pressure through both angiotensin-II AT1 receptor-dependent and -independent mechanisms. PMID- 25122008 TI - A supersandwich electrochemiluminescence immunosensor based on mimic intramolecular interaction for sensitive detection of proteins. AB - An electrochemiluminescence (ECL) immunoassay protocol was developed based on mimic-intramolecular interaction for sensitive detection of prostate specific antigen (PSA). It was constructed by integrating the ECL luminophore (tris(4,4' dicarboxylicacid-2,2'-bipyridyl)-ruthenium(ii)dichloride (Ru(dcbpy)3(2+))) and coreactant (histidine) into the supersandwich DNA structure. This strategy was more effective in amplifying the ECL signal by shortening the electronic transmission distance, improving the ECL luminous stability and enhancing the ECL luminous efficiency. The ECL matrices denoted as MWCNTs@PDA-AuNPs were fabricated through spontaneous oxidative polymerization of dopamine (DA) on multiwalled carbon nanotubes (MWCNTs) and reducing HAuCl4 to produce gold nanoparticles (AuNPs) by DA simultaneously. Then, the prepared matrices were applied to bind capture antibodies. Moreover, supersandwich Ab2 bioconjugate was designed using a PAMAM dendrimer to immobilize the detection antibody and supersandwich DNA structure. The PAMAM dendrimer, with a plurality of secondary and tertiary amine groups, not only facilitated high-density immobilization of the detection antibody and supersandwich DNA structure, but also greatly amplified the ECL signal of Ru(dcbpy)3(2+). The supersandwich DNA structure contained multiple Ru(dcbpy)3(2+) and histidine, further amplifying the ECL signal. The proposed supersandwich immunosensor showed high sensitivity with a detection limit of 4.2 fg mL(-1) and a wide linear range of 0.01 pg mL(-1)-40.00 ng mL(-1). With the excellent stability, satisfying precision and reproducibility, the proposed immunosensor indicates promising practicability for clinical diagnosis. PMID- 25122009 TI - Workers: the climate canaries. PMID- 25122007 TI - Lymphocyte Activation Gene-3 (LAG-3) negatively regulates environmentally-induced autoimmunity. AB - Environmental factors including drugs, mineral oils and heavy metals such as lead, gold and mercury are triggers of autoimmune diseases in animal models or even in occupationally exposed humans. After exposure to subtoxic levels of mercury (Hg), genetically susceptible strains of mice develop an autoimmune disease characterized by the production of highly specific anti-nucleolar autoantibodies, hyperglobulinemia and nephritis. However, mice can be tolerized to the disease by a single low dose administration of Hg. Lymphocyte Activation Gene-3 (LAG-3) is a CD4-related, MHC-class II binding molecule expressed on activated T cells and NK cells which maintains lymphocyte homeostatic balance via various inhibitory mechanisms. In our model, administration of anti-LAG-3 monoclonal antibody broke tolerance to Hg resulting in autoantibody production and an increase in serum IgE level. In addition, LAG-3-deficient B6.SJL mice not only had increased susceptibility to Hg-induced autoimmunity but were also unresponsive to tolerance induction. Conversely, adoptive transfer of wild-type CD4(+) T cells was able to partially rescue LAG-3-deficient mice from the autoimmune disease. Further, in LAG-3-deficient mice, mercury elicited higher amounts of IL-6, IL-4 and IFN-gamma, cytokines known to play a critical role in mercury-induced autoimmunity. Therefore, we conclude that LAG-3 exerts an important regulatory effect on autoimmunity elicited by a common environmental pollutant. PMID- 25122010 TI - Epigenome: biosensor of cumulative exposure to chemical and nonchemical stressors related to environmental justice. AB - Understanding differential disease susceptibility requires new tools to quantify the cumulative effects of environmental stress. Evidence suggests that social, physical, and chemical stressors can influence disease through the accumulation of epigenetic modifications. Geographically stable epigenetic alterations could identify plausible mechanisms for health disparities among the disadvantaged and poor. Relations between neighborhood-specific epigenetic markers and disease would identify the most appropriate targets for medical and environmental intervention. Complex interactions among genes, the environment, and disease require the examination of how epigenetic changes regulate susceptibility to environmental stressors. Progress in understanding disparities in disease susceptibility may depend on assessing the cumulative effect of environmental stressors on genetic substrates. We highlight key concepts regarding the interface between environmental stress, epigenetics, and chronic disease. PMID- 25122011 TI - Why is life expectancy declining among low-educated women in the United States? PMID- 25122012 TI - Is science public health's BFF? PMID- 25122013 TI - Dentist supply and children's oral health in the United States. AB - OBJECTIVES: We evaluated the relationship between dentist supply and children's oral health and explored heterogeneity by children's age and urbanicity. METHODS: We obtained data from the 2007 National Survey of Children's Health (>27,000 children aged 1-10 years; >23,000 children aged 11-17 years). We estimated the association between state-level dentist supply and multiple measures of children's oral health using regression analysis adjusting for several child, family, and population-level characteristics. RESULTS: Dentist supply was significantly related to better oral health outcomes among children aged 1 to 10 years. The odds of decay and bleeding gums were lower by more than 50% (odds ratio [OR]=0.46; 95% CI=0.23, 0.95) and 80% (OR=0.18; 95% CI=0.05, 0.76), respectively, with an additional dentist per 1000 population. The odds of a worse maternal rating of child's dental health on a 5-category scale from poor to excellent were lower by about 50% in this age group with an additional dentist per 1000 population (OR=0.51; 95% CI=0.29, 0.91). We observed associations only for children in urban settings. CONCLUSIONS: Dentist supply is associated with improved oral health for younger children in urban settings. PMID- 25122014 TI - Insidious trends and social/environmental justice: public health's challenge for responding to hazard events. PMID- 25122016 TI - Fleming et al. respond. PMID- 25122015 TI - Use of research evidence in state policymaking for childhood obesity prevention in Minnesota. AB - OBJECTIVES: We describe how scientific evidence about obesity has been used in Minnesota legislative materials to understand how research evidence might more effectively be translated into policymaking. METHODS: We selected 13 obesity related bills introduced from 2007 to 2011 in Minnesota. Using state archives, we collected all legislative committee meeting materials and floor testimony related to each bill. We used a coding instrument to systematically analyze the content of a sample of 109 materials for their use of research evidence and non-research based information. RESULTS: Research evidence was mentioned in 41% of all legislative materials. Evidence was often used to describe the prevalence or consequences of obesity or policy impacts but not to describe health disparities. In 45% of materials that cited evidence, no source of evidence was indicated. By contrast, 92% of materials presented non-research-based information, such as expert beliefs, constituent opinion, political principles, and anecdotes. CONCLUSIONS: Despite an abundance of available research evidence on obesity, less than half of legislative materials cited any such evidence in discussions around obesity-related bills under consideration in Minnesota. PMID- 25122017 TI - The alcohol policy environment and policy subgroups as predictors of binge drinking measures among US adults. AB - OBJECTIVES: We examined the relationships of the state-level alcohol policy environment and policy subgroups with individual-level binge drinking measures. METHODS: We used generalized estimating equations regression models to relate the alcohol policy environment based on data from 29 policies in US states from 2004 to 2009 to 3 binge drinking measures in adults from the 2005 to 2010 Behavioral Risk Factor Surveillance System surveys. RESULTS: A 10 percentage point higher alcohol policy environment score, which reflected increased policy effectiveness and implementation, was associated with an 8% lower adjusted odds of binge drinking and binge drinking 5 or more times, and a 10% lower adjusted odds of consuming 10 or more drinks. Policies that targeted the general population rather than the underage population, alcohol consumption rather than impaired driving, and raising the price or reducing the availability of alcohol had the strongest independent associations with reduced binge drinking. Alcohol taxes and outlet density accounted for approximately half of the effect magnitude observed for all policies. CONCLUSIONS: A small number of policies that raised alcohol prices and reduced its availability appeared to affect binge drinking. PMID- 25122018 TI - The tobacco industry, researchers, and ethical access to UK Biobank: using the public interest and public good. AB - We have asked whether the strategic purpose of the tobacco industry is something that a public resource, such as UK Biobank, should support. Tobacco industry health research has been known to work irreconcilably with the purposes of such institutions, which can be surmised as for the public good and defined to improve the provision, diagnosis, and treatment of illness and the promotion of health throughout society. We have isolated possible conflicts of interest that underlie vested research agendas of the tobacco industry and that may extend to tobacco industry-funded researchers. With respect to research, we find that the tobacco industry is entirely at odds with the purposes of public biobanking. PMID- 25122020 TI - Moving upstream: why rehabilitative justice in military discharge proceedings serves a public health interest. AB - The cultural divide between US military and civilian institutions amplifies the consequences of military discharge status on public health and criminal justice systems in a manner that is invisible to a larger society. Prompt removal of problematic wounded warriors through retributive justice is more expedient than lengthy mental health treatment. Administrative and punitive discharges usually preclude Department of Veterans Affairs eligibility, posing a heavy public health burden. Moving upstream--through military rehabilitative justice addressing military offenders' mental health needs before discharge--will reduce the downstream consequences of civilian maladjustment and intergenerational transmission of mental illness. The public health community can play an illuminating role by gathering data about community effect and by advocating for policy change at Department of Veterans Affairs and community levels. PMID- 25122019 TI - Systematic review of the effect of pictorial warnings on cigarette packages in smoking behavior. AB - We used a structured approach to assess whether active smokers presented with pictorial warnings on cigarette packages (PWCP) had a higher probability of quitting, reducing, and attempting to quit smoking than did unexposed smokers. We identified 21 articles from among nearly 2500 published between 1993 and 2013, prioritizing coverage over relevance or quality because we expected to find only a few studies with behavioral outcomes. We found very large heterogeneity across studies, poor or very poor methodological quality, and generally null or conflicting findings for any explored outcome. The evidence for or against the use of PWCP is insufficient, suggesting that any effect of PWCP on behavior would be modest. Determining the single impact of PWCP on behavior requires studies with strong methodological designs and longer follow-up periods. PMID- 25122021 TI - Patterns of visit attendance in the nurse-family partnership program. AB - OBJECTIVES: We examined visit attendance patterns in the Memphis trial of the Nurse-Family Partnership and associations between these patterns and family characteristics, outcomes, and treatment-control differences in outcomes. METHODS: We employed repeated measures latent class analysis to identify attendance patterns among the 228 mothers assigned to receive home nurse visits during pregnancy and until the child was aged 2 years, associated background characteristics, outcomes, and treatment-control differences by visit class. Home visits were conducted from June 1990 to March 1994. We collected outcome data from May 1992 to April 1994 and July 2003 to December 2006. RESULTS: We identified 3 visit attendance patterns. High attenders (48%) had the most visits and good outcomes. Low attenders (33%) had the most education and the best outcomes. Increasing attenders (18%) had the fewest completed visits during pregnancy, the poorest intake characteristics, and the poorest outcomes. Treatment-control group differences varied by class, with high and low attenders having better outcomes on some measures than did their control group counterparts. CONCLUSIONS: Three patterns were associated with distinct groups of mothers with different long-term outcomes. Further examination and use of patterns to classify mothers and prioritize resources may improve efficiency in the Nurse-Family Partnership. PMID- 25122022 TI - Integrating health into disaster risk reduction strategies: key considerations for success. AB - The human and financial costs of disasters are vast. In 2011, disasters were estimated to have cost $378 billion worldwide; disasters have affected 64% of the world's population since 1992. Consequently, disaster risk reduction strategies have become increasingly prominent on national and international policy agendas. However, the function of health in disaster risk reduction strategies often has been restricted to emergency response. To mitigate the effect of disasters on social and health development goals (such as risk reduction Millennium Development Goals) and increase resilience among at-risk populations, disaster strategies should assign the health sector a more all-encompassing, proactive role. We discuss proposed methods and concepts for mainstreaming health in disaster risk reduction and consider barriers faced by the health sector in this field. PMID- 25122023 TI - On the value of the "Man Up Monday" campaign. PMID- 25122025 TI - Reproductive rights denied: the Hyde Amendment and access to abortion for Native American women using Indian health service facilities. AB - Restrictions on the use of federal funds to provide abortions have limited the access to abortion services for Native American women receiving care at Indian Health Service facilities. Current data suggest that the vast majority of Indian Health Service facilities are unequipped to provide abortions under any circumstances. Native American women experience disproportionately high rates of sexual assault and unintended pregnancy. Hyde Amendment restrictions systematically infringe on the reproductive rights of Native American women and present a pressing public health policy concern. PMID- 25122024 TI - Implementation of tobacco cessation quitline practices in the United States and Canada. AB - OBJECTIVES: We examined relationships between implementation of tobacco quitline practices, levels of evidence of practices, and quitline reach and spending. METHODS: In June and July 2009, a total of 176 quitline funders and providers in the United States and Canada completed a survey on quitline practices, in particular quitline-level implementation for the reported practices. From these data, we selected and categorized evidence-based and emerging quitline practices by the strength of the evidence for each practice to increase quitline efficacy and reach. RESULTS: The proportion of quitlines implementing each practice ranged from 3% (text messaging) to 92% (providing a multiple-call protocol). Implementation of practices showing higher levels of evidence for increasing either reach or efficacy showed moderate but significant positive correlations with both reach outcomes and spending levels. The strongest correlation was between reach outcomes and spending levels (r=0.80; P<.01). CONCLUSIONS: The strong relationship between quitline spending and reach reinforces the need to increase quitline funding to levels commensurate with national cessation goals. PMID- 25122026 TI - Evaluating the implementation process of a citywide smoke-free multiunit housing ordinance: insights from community stakeholders. AB - We evaluated the implementation process of Richmond, California's citywide smoke free multiunit housing ordinance. We conducted semistructured focus groups with multiunit housing tenants, owners, and managers. Residents understood the harms of secondhand smoke but lacked accurate information about the ordinance and questioned its enforceability. They shared concerns that the city lacked cessation resources for smokers wishing to quit because of the ordinance. To increase compliance with the ordinance, tenants, owners, and managers need accurate information. PMID- 25122027 TI - Effects of statewide job losses on adolescent suicide-related behaviors. AB - OBJECTIVES: We investigated the impact of statewide job loss on adolescent suicide-related behaviors. METHODS: We used 1997 to 2009 data from the Youth Risk Behavior Survey and the Bureau of Labor Statistics to estimate the effects of statewide job loss on adolescents' suicidal ideation, suicide attempts, and suicide plans. Probit regression models controlled for demographic characteristics, state of residence, and year; samples were divided according to gender and race/ethnicity. RESULTS: Statewide job losses during the year preceding the survey increased girls' probability of suicidal ideation and suicide plans and non-Hispanic Black adolescents' probability of suicidal ideation, suicide plans, and suicide attempts. Job losses among 1% of a state's working-age population increased the probability of girls and Blacks reporting suicide-related behaviors by 2 to 3 percentage points. Job losses did not affect the suicide-related behaviors of boys, non-Hispanic Whites, or Hispanics. The results were robust to the inclusion of other state economic characteristics. CONCLUSIONS: As are adults, adolescents are affected by economic downturns. Our findings show that statewide job loss increases adolescent girls' and non Hispanic Blacks' suicide-related behaviors. PMID- 25122029 TI - Adverse outcomes among homeless adolescents and young adults who report a history of traumatic brain injury. AB - OBJECTIVES: We examined the prevalence of self-reported traumatic brain injury (TBI) among homeless young people and explored whether sociodemographic characteristics, mental health diagnoses, substance use, exposure to violence, or difficulties with activities of daily living (ADLs) were associated with TBI. METHODS: We analyzed data from the Wilder Homelessness Study, in which participants were recruited in 2006 and 2009 from streets, shelters, and locations in Minnesota that provide services to homeless individuals. Participants completed 30-minute interviews to collect information about history of TBI, homelessness, health status, exposure to violence (e.g., childhood abuse, assault), and other aspects of functioning. RESULTS: Of the 2732 participating adolescents and young adults, 43% reported a history of TBI. Participants with TBI became homeless at a younger age and were more likely to report mental health diagnoses, substance use, suicidality, victimization, and difficulties with ADLs. The majority of participants (51%) reported sustaining their first injury prior to becoming homeless or at the same age of their first homeless episode (10%). CONCLUSIONS: TBI occurs frequently among homeless young people and is a marker of adverse outcomes such as mental health difficulties, suicidal behavior, substance use, and victimization. PMID- 25122028 TI - Enhancing diversity in the public health research workforce: the research and mentorship program for future HIV vaccine scientists. AB - OBJECTIVES: We developed and evaluated a novel National Institutes of Health sponsored Research and Mentorship Program for African American and Hispanic medical students embedded within the international, multisite HIV Vaccine Trials Network, and explored its impact on scientific knowledge, acquired skills, and future career plans. METHODS: Scholars conducted social, behavioral, clinical, or laboratory-based research projects with HIV Vaccine Trials Network investigators over 8 to 16 weeks (track 1) or 9 to 12 months (track 2). We conducted an in depth, mixed-methods evaluation of the first 2 cohorts (2011-2013) to identify program strengths, areas for improvement, and influence on professional development. RESULTS: A pre-post program assessment demonstrated increases in self-reported knowledge, professional skills, and interest in future HIV vaccine research. During in-depth interviews, scholars reported that a supportive, centrally administered program; available funding; and highly involved mentors and staff were keys to the program's early success. CONCLUSIONS: A multicomponent, mentored research experience that engages medical students from underrepresented communities and is organized within a clinical trials network may expand the pool of diverse public health scientists. Efforts to sustain scholar interest over time and track career trajectories are warranted. PMID- 25122030 TI - Analysis of the accuracy of weight loss information search engine results on the internet. AB - OBJECTIVES: We systematically identified and evaluated the quality and comprehensiveness of online information related to weight loss that users were likely to access. METHODS: We evaluated the content quality, accessibility of the information, and author credentials for Web sites in 2012 that were identified from weight loss specific queries that we generated. We scored the content with respect to available evidence-based guidelines for weight loss. RESULTS: One hundred three Web sites met our eligibility criteria (21 commercial, 52 news/media, 7 blogs, 14 medical, government, or university, and 9 unclassified sites). The mean content quality score was 3.75 (range=0-16; SD=2.48). Approximately 5% (4.85%) of the sites scored greater than 8 (of 12) on nutrition, physical activity, and behavior. Content quality score varied significantly by type of Web site; the medical, government, or university sites (mean=4.82, SD=2.27) and blogs (mean=6.33, SD=1.99) had the highest scores. Commercial (mean=2.37, SD=2.60) or news/media sites (mean=3.52, SD=2.31) had the lowest scores (analysis of variance P<.005). CONCLUSIONS: The weight loss information that people were likely to access online was often of substandard quality because most comprehensive and quality Web sites ranked too low in search results. PMID- 25122032 TI - On Agent Orange in Vietnam. PMID- 25122031 TI - Impact of an exercise intervention on physical activity during pregnancy: the behaviors affecting baby and you study. AB - OBJECTIVES: We examined the impact of a prenatal exercise intervention on physical activity in 260 women at risk for gestational diabetes mellitus. METHODS: We randomized participants in the Behaviors Affecting Baby and You (BABY) Study, which took place from 2007 to 2012, to either a 12-week individually tailored, motivationally matched exercise intervention (n=132) or to a comparison health and wellness intervention (n=128). We assessed physical activity with the Pregnancy Physical Activity Questionnaire. We used linear mixed models to evaluate the impact of the interventions on change in physical activity according to intensity and type, total walking, and sedentary behavior. RESULTS: Compared with the health and wellness arm, the exercise arm had significantly greater increases in sports or exercise activity (0.3 vs 5.3 metabolic equivalent of task [MET] hours/week; P<.001), and smaller declines in total activity (-42.7 vs -2.1 MET hours/week; P=.02) and activities of moderate to vigorous intensity ( 30.6 vs -10.6 MET hours/week; P=.05), and was more likely to achieve recommended guidelines for physical activity (odds ratio=2.12; 95% confidence interval=1.45, 3.10). CONCLUSIONS: These findings extend the previous literature by demonstrating the benefits of a clinically feasible exercise intervention in an ethnically and socio-economically diverse population. Given the increased risk of adverse maternal health outcomes in ethnic minority groups, these findings may have important implications for reducing health disparities. PMID- 25122034 TI - Research informs abortion care policy change in California. PMID- 25122035 TI - Reversibly tunable upconversion luminescence by host-guest chemistry. AB - Tuning upconversion (UPC) luminescence using external stimuli and fields, as well as chemical reactions, is expected to lead to novel and efficient optical sensors. Herein, highly tunable UPC luminescence was achieved through a host guest chemistry approach. Specifically, interlayer ion exchange reactions reversibly tuned the emission intensity and green-red color of Er/Yb-codoped A2La2Ti3O10 layered perovskite, where A corresponds to proton and alkali metal ions, enabling the visualization of host-guest interactions and reactions. PMID- 25122036 TI - Repair-dependent cell radiation survival and transformation: an integrated theory. AB - The repair-dependent model of cell radiation survival is extended to include radiation-induced transformations. The probability of transformation is presumed to scale with the number of potentially lethal damages that are repaired in a surviving cell or the interactions of such damages. The theory predicts that at doses corresponding to high survival, the transformation frequency is the sum of simple polynomial functions of dose; linear, quadratic, etc, essentially as described in widely used linear-quadratic expressions. At high doses, corresponding to low survival, the ratio of transformed to surviving cells asymptotically approaches an upper limit. The low dose fundamental- and high dose plateau domains are separated by a downwardly concave transition region. Published transformation data for mammalian cells show the high-dose plateaus predicted by the repair-dependent model for both ultraviolet and ionizing radiation. For the neoplastic transformation experiments that were analyzed, the data can be fit with only the repair-dependent quadratic function. At low doses, the transformation frequency is strictly quadratic, but becomes sigmodial over a wider range of doses. Inclusion of data from the transition region in a traditional linear-quadratic analysis of neoplastic transformation frequency data can exaggerate the magnitude of, or create the appearance of, a linear component. Quantitative analysis of survival and transformation data shows good agreement for ultraviolet radiation; the shapes of the transformation components can be predicted from survival data. For ionizing radiations, both neutrons and x-rays, survival data overestimate the transforming ability for low to moderate doses. The presumed cause of this difference is that, unlike UV photons, a single x-ray or neutron may generate more than one lethal damage in a cell, so the distribution of such damages in the population is not accurately described by Poisson statistics. However, the complete sigmodial dose-response data for neoplastic transformations can be fit using the repair-dependent functions with all parameters determined only from transformation frequency data. PMID- 25122033 TI - An education in contrast: state-by-state assessment of school immunization records requirements. AB - OBJECTIVES: We reviewed the complexities of school-related immunization policies, their relation to immunization information systems (IIS) and immunization registries, and the historical context to better understand this convoluted policy system. METHODS: We used legal databases (Lexis-Nexis and Westlaw) to identify school immunization records policies for 50 states, 5 cities, and the District of Columbia (Centers for Disease Control and Prevention "grantees"). The original search took place from May to September 2010 (cross-referenced in July 2013 with the list on http://www.immunize.org/laws ). We describe the requirements, agreement with IIS policies, and penalties for policy violations. RESULTS: We found a complex web of public health, medical, and education-directed policies, which complicates immunization data sharing. Most (79%) require records of immunizations for children to attend school or for a child-care institution licensure, but only a few (11%) require coordination between IIS and schools or child-care facilities. CONCLUSIONS: To realize the full benefit of IIS investment, including improved immunization and school health program efficiencies, IIS and school immunization records policies must be better coordinated. States with well-integrated policies may serve as models for effective harmonization. PMID- 25122037 TI - Molecular xenomonitoring using mosquitoes to map lymphatic filariasis after mass drug administration in American Samoa. AB - BACKGROUND: Mass drug administration (MDA) programs have dramatically reduced lymphatic filariasis (LF) incidence in many areas around the globe, including American Samoa. As infection rates decline and MDA programs end, efficient and sensitive methods for detecting infections are needed to monitor for recrudescence. Molecular methods, collectively termed 'molecular xenomonitoring,' can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested mosquitoes trapped throughout the inhabited islands of American Samoa to identify areas of possible continuing LF transmission after completion of MDA. METHODOLOGY/PRINCIPLE FINDINGS: Mosquitoes were collected using BG Sentinel traps from most of the villages on American Samoa's largest island, Tutuila, and all major villages on the smaller islands of Aunu'u, Ofu, Olosega, and Ta'u. Real time PCR was used to detect Wuchereria bancrofti DNA in pools of <= 20 mosquitoes, and PoolScreen software was used to infer territory-wide prevalences of W. bancrofti DNA in the mosquitoes. Wuchereria bancrofti DNA was found in mosquitoes from 16 out of the 27 village areas sampled on Tutuila and Aunu'u islands but none of the five villages on the Manu'a islands of Ofu, Olosega, and Ta'u. The overall 95% confidence interval estimate for W. bancrofti DNA prevalence in the LF vector Ae. polynesiensis was 0.20-0.39%, and parasite DNA was also detected in pools of Culex quinquefasciatus, Aedes aegypti, and Aedes (Finlaya) spp. CONCLUSIONS/SIGNIFICANCE: Our results suggest low but widespread prevalence of LF on Tutuila and Aunu'u where 98% of the population resides, but not Ofu, Olosega, and Ta'u islands. Molecular xenomonitoring can help identify areas of possible LF transmission, but its use in the LF elimination program in American Samoa is limited by the need for more efficient mosquito collection methods and a better understanding of the relationship between prevalence of W. bancrofti DNA in mosquitoes and infection and transmission rates in humans. PMID- 25122038 TI - Hippocampal volume and the rapid antidepressant effect of ketamine. AB - Accumulating evidence underscores the utility of ketamine in treating severely treatment-resistant depressed patients. We investigated the relationship between the rapid antidepressant effects of ketamine and hippocampal volume, a biomarker of antidepressant treatment outcome. We gave 16 medication-free, major depressive disorder (MDD) patients a single, sub-anesthetic dose infusion of ketamine (0.5 mg/kg, over 40 min). We assessed depression severity pre-treatment, and at 24 h post-treatment, with the Montgomery-Asberg Depression Rating Scale (MADRS). Prior to treatment, patients underwent magnetic resonance imaging (MRI) to estimate their hippocampal volume: We obtained viable MRI data in 13 patients. Delta MADRS (post- minus pre-treatment) was significantly correlated with the pre-treatment volumes of the left hippocampus (r = 0.66; p = 0.01), but not the right hippocampus (r = 0.49; p = 0.09). The correlation between delta MADRS and the left hippocampus remained high (r > 0.6; p = 0.13), after controlling for several demographic and clinical variables, although the p value increased due to the reduced degree of freedom (df = 5). Ketamine exerts enhanced antidepressant effects in patients with a relatively smaller hippocampus, a patient population that has been repeatedly shown to be refractory to traditional antidepressants. PMID- 25122039 TI - Analysis of sociability and preference for social novelty in the acute and subchronic phencyclidine rat. AB - Both acute and sub-chronic phencyclidine administration produce behavioural and pathophysiological changes that resemble some features of schizophrenia. The present study aimed to determine if acute and sub-chronic phencyclidine treatment in male rats produces deficits in sociability and social novelty preference, which may reflect aspects of the negative symptomatology observed in schizophrenia. Rats were treated with phencyclidine acutely (2 or 5 mg/kg) or subchronically (2 or 5 mg/kg bi-daily for one week followed by a one week wash out period) or vehicle. Social affiliative behaviour was assessed using the sociability and preference for social novelty paradigm where social interaction time was measured in (a) a chamber containing an unfamiliar conspecific vs an empty chamber (sociability), or (b) a chamber containing an unfamiliar conspecific vs a chamber containing a familiar conspecific (preference for social novelty). Results showed that acute administration of phencyclidine produced a reduction in measures of sociability but had no effect on preference for social novelty while sub-chronic administration of phencyclidine had no effect on sociability or social novelty. This study provides further evidence for the usefulness of phencyclidine models in modelling the symptomatology of schizophrenia. PMID- 25122040 TI - Effects of tobacco smoke constituents, anabasine and anatabine, on memory and attention in female rats. AB - Nicotine has been well characterized to improve memory and attention. Nicotine is the primary, but not only neuroactive compound in tobacco. Other tobacco constituents such as anabasine and anatabine also have agonist actions on nicotinic receptors. The current study investigated the effects of anabasine and anatabine on memory and attention. Adult female Sprague-Dawley rats were trained on a win-shift spatial working and reference memory task in the 16-arm radial maze or a visual signal detection operant task to test attention. Acute dose effect functions of anabasine and anatabine over two orders of magnitude were evaluated for both tasks. In the radial-arm maze memory test, anabasine but not anatabine significantly reduced the memory impairment caused by the NMDA antagonist dizocilpine (MK-801). In the signal detection attentional task, anatabine but not anabasine significantly attenuated the attentional impairment caused by dizocilpine. These studies show that non-nicotine nicotinic agonists in tobacco, similar to nicotine, can significantly improve memory and attentional function. Both anabasine and anatabine produced cognitive improvement, but their effectiveness differed with regard to memory and attention. Follow-up studies with anabasine and anatabine are called for to determine their efficacy as therapeutics for memory and attentional dysfunction. PMID- 25122041 TI - Central noradrenergic mechanisms and the acute stress response during painful stimulation. AB - Events that threaten tissue integrity including noxious stimulation activate central noradrenergic circuits, particularly locus coeruleus and its projections. Recent advances in theory hold that an adaptive, defensive shift in brain activity takes place in response to threat. In principle, this shift may accentuate the autonomic and central biomarkers of the perception of painful events and the experience of pain itself. We have examined the effects of an alpha-2 agonist on pupil dilation responses, skin conductance responses, near field somatosensory evoked potentials and pain reports in normal volunteers undergoing repeated trials of painful fingertip stimulation delivered at low, medium and high intensities. In a double-blinded study, 114 healthy male and female volunteers underwent repeated noxious stimulation under baseline, placebo and active drug conditions where the active drug was the alpha-2 agonist tizanidine 4 mg. In contrast to baseline and placebo conditions, tizanidine 4 mg significantly reduced the magnitudes of the mean pupil dilation response, the mean skin conductance response, the mean near field somatosensory evoked potential peak-to-peak amplitude and the mean pain intensity rating. Stimulus intensity significantly altered all three biomarkers and the pain report in a graded fashion. There were no sex differences. These findings support the hypotheses that painful events activate central noradrenergic circuits, and that these circuits play a role in the autonomic and central arousal associated with pain. PMID- 25122042 TI - Potentiation of latent inhibition by haloperidol and clozapine is attenuated in Dopamine D2 receptor (Drd-2)-deficient mice: do antipsychotics influence learning to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms? AB - Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it has previously been shown that Drd-2 is not necessary for antipsychotic drugs to reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure of learning to ignore irrelevant stimuli. Weiner's 'two-headed' model indicates that antipsychotics not only reverse LI disruption, 'disrupted LI', but also potentiate LI when low/absent in controls, 'persistent' LI. We investigated whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2 -/- mice, suggesting moderation of this effect of antipsychotics in the absence of Drd-2. Haloperidol potentiated LI similarly in both Drd1 -/- and wild-type mice, indicating no such moderation in Drd1 -/-. These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced. Identification of the non Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis. PMID- 25122045 TI - Electrophysiological correlates of alcohol- and non-alcohol-related stimuli processing in binge drinkers: a follow-up study. AB - BACKGROUND: The continuation of binge drinking is associated with the development of neurocognitive brain abnormalities similar to those observed in patients with alcohol dependence. Alcohol cue reactivity constitutes a risk marker for alcohol dependence. Through event-related potentials (ERPs), we aimed to examine its potential presence as well as its evolution over time in binge drinkers in a one year period. METHODS: ERPs were recorded during a visual oddball task in which controls (n=15) and binge drinkers (n=15) had to detect infrequent deviant stimuli (related or unrelated to alcohol) among frequent standard stimuli. The test was performed twice with a one-year interval in order to explore the long lasting influence of drinking habits. RESULTS: Contrary to the controls, binge drinkers showed significantly reduced amplitudes of the P1 component for both alcohol and non-alcohol-related cues and of the P3 component only for neutral cues in the second assessment compared with the first. CONCLUSION: The continuation of binge drinking over one year is associated with the development of brain functional abnormalities (indexed by the P1 component) as well as a higher reactivity to alcohol-related stimuli and/or a decreased reactivity to non alcohol-related stimuli (indexed by the P3 component). PMID- 25122043 TI - Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity in the rat hippocampus. AB - Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5 HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor. Vortioxetine has been shown to improve cognitive performance in several preclinical rat models and in patients with major depressive disorder. Here we investigated the mechanistic basis for these effects by studying the effect of vortioxetine on synaptic transmission, long-term potentiation (LTP), a cellular correlate of learning and memory, and theta oscillations in the rat hippocampus and frontal cortex. Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3 receptor antagonism. Vortioxetine also enhanced LTP in the CA1 region of the hippocampus. Finally, vortioxetine increased fronto-cortical theta power during active wake in whole animal electroencephalographic recordings. In comparison, the selective SERT inhibitor escitalopram showed no effect on any of these measures. Taken together, our results indicate that vortioxetine can increase pyramidal cell output, which leads to enhanced synaptic plasticity in the hippocampus. Given the central role of the hippocampus in cognition, these findings may provide a cellular correlate to the observed preclinical and clinical cognition-enhancing effects of vortioxetine. PMID- 25122044 TI - Effects of ecstasy on cooperative behaviour and perception of trustworthiness: a naturalistic study. AB - BACKGROUND: Acute recreational use of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') can promote pro-social effects which may alter interpersonal perceptions. AIMS: To explore such effects, this study investigated whether acute recreational use of ecstasy was associated with changes in individual perception of trustworthiness of people's faces and co-operative behaviours. METHOD: An independent group, repeated measures design was used in which 17 ecstasy users were tested on the night of drug use (day 0) and again three days later (day 3); 22 controls were tested on parallel days. On each day, participants rated the trustworthiness of 66 faces, carried out three co-operative behaviour tasks (public good; dictator; ultimatum game) and completed mood self-ratings. RESULTS: Acute ecstasy use was associated with increased face trustworthiness ratings and increased cooperative behaviour on the dictator and ultimatum games; on day 3 there were no group differences on any task. Self-ratings showed the standard acute ecstasy effects (euphoria, energy, jaw clenching) with negative effects (less empathy, compassion, more distrust, hostility) emerging on day 3. CONCLUSIONS: Our findings of increased perceived trustworthiness and co-operative behaviours following use of ecstasy suggest that a single dose of the drug enhances aspects of empathy. This may in turn contribute to its popularity as a recreational drug and potentially to its enhancement of the therapeutic alliance in psychotherapy. PMID- 25122046 TI - CYP2C19 variation, not citalopram dose nor serum level, is associated with QTc prolongation. AB - Recently, a FDA Safety Communication warned of a dose-dependent risk for QTc prolongation with citalopram, which is metabolized by CYP2C19 of the cytochrome P450 system. We investigate associations between citalopram and escitalopram dose, serum concentration, CYP2C19 phenotype, and QTc. We undertook a retrospective chart review of citalopram or escitalopram patients with the inclusion criteria of consistent medication dose, CYP2C19 phenotype (extensive metabolizers [EM], intermediate metabolizers [IM], poor metabolizers [PM]), and QTc interval on ECG. We further identified 42 citalopram users with citalopram serum concentration measurements and ECG. Regression and one-way ANOVA were used to examine the relationship between citalopram dose, citalopram serum concentration, CYP2C19 phenotype, and QTc interval. Of 75 citalopram patients, the EM group had significantly shorter QTc intervals than a combined IM+PM group (427.1+/-23.6 ms vs. 440.1+/-26.6 ms, one-tailed t-test, p=0.029). In the 80 escitalopram cohort, there was no significant difference in QTc between phenotype groups. There was no statistical correlation between citalopram (p=0.62) or escitalopram (p=0.30) dose and QTc. QTc was not associated with citalopram serum level (p=0.45). In contrast to the FDA warning, this study found no association between citalopram/escitalopram dose and QTc. However, PM of the drug tended to have longer QTc intervals. Our findings suggest cytochrome P450 genotyping in select patients may be helpful to guide medication optimization while limiting harmful effects. PMID- 25122047 TI - A radical approach to balancing the tides of tubular flow. PMID- 25122049 TI - Angiotensin induces a pressor regulating role for collecting duct renin. PMID- 25122048 TI - Collecting duct-specific knockout of renin attenuates angiotensin II-induced hypertension. AB - The physiological and pathophysiological significance of collecting duct (CD) derived renin, particularly as it relates to blood pressure (BP) regulation, is unknown. To address this question, we generated CD-specific renin knockout (KO) mice and examined BP and renal salt and water excretion. Mice containing loxP flanked exon 1 of the renin gene were crossed with mice transgenic for aquaporin 2-Cre recombinase to achieve CD-specific renin KO. Compared with controls, CD renin KO mice had 70% lower medullary renin mRNA and 90% lower renin mRNA in microdissected cortical CD. Urinary renin levels were significantly lower in KO mice (45% of control levels) while plasma renin concentration was significantly higher in KO mice (63% higher than controls) during normal-Na intake. While no observable differences were noted in BP between the two groups with varying Na intake, infusion of angiotensin II at 400 ng.kg(-1).min(-1) resulted in an attenuated hypertensive response in the KO mice (mean arterial pressure 111 +/- 4 mmHg in KO vs. 128 +/- 3 mmHg in controls). Urinary renin excretion and epithelial Na(+) channel (ENaC) remained significantly lower in the KO mice following ANG II infusion compared with controls. Furthermore, membrane associated ENaC protein levels were significantly lower in KO mice following ANG II infusion. These findings suggest that CD renin modulates BP in ANG II-infused hypertension and these effects are associated with changes in ENaC expression. PMID- 25122051 TI - WHO gives go ahead for experimental treatments to be used in Ebola outbreak. PMID- 25122050 TI - Oxidative stress-induced alterations in PPAR-gamma and associated mitochondrial destabilization contribute to kidney cell apoptosis. AB - The mechanism(s) underlying renoprotection by peroxisome proliferator-activated receptor (PPAR)-gamma agonists in diabetic and nondiabetic kidney disease are not well understood. Mitochondrial dysfunction and oxidative stress contribute to kidney disease. PPAR-gamma upregulates proteins required for mitochondrial biogenesis. Our aim was to determine whether PPAR-gamma has a role in protecting the kidney proximal tubular epithelium (PTE) against mitochondrial destabilisation and oxidative stress. HK-2 PTE cells were subjected to oxidative stress (0.2-1.0 mM H2O2) for 2 and 18 h and compared with untreated cells for apoptosis, mitosis (morphology/biomarkers), cell viability (MTT), superoxide (dihydroethidium), mitochondrial function (MitoTracker red and JC-1), ATP (luminescence), and mitochondrial ultrastructure. PPAR-gamma, phospho-PPAR-gamma, PPAR-gamma coactivator (PGC)-1alpha, Parkin (Park2), p62, and light chain (LC)3beta were investigated using Western blots. PPAR-gamma was modulated using the agonists rosiglitazone, pioglitazone, and troglitazone. Mitochondrial destabilization increased with H2O2concentration, ATP decreased (2 and 18 h; P < 0.05), Mitotracker red and JC-1 fluorescence indicated loss of mitochondrial membrane potential, and superoxide increased (18 h, P < 0.05). Electron microscopy indicated sparse mitochondria, with disrupted cristae. Mitophagy was evident at 2 h (Park2 and LC3beta increased; p62 decreased). Impaired mitophagy was indicated by p62 accumulation at 18 h (P < 0.05). PPAR-gamma expression decreased, phospho-PPAR-gamma increased, and PGC-1alpha decreased (2 h), indicating aberrant PPAR-gamma activation and reduced mitochondrial biogenesis. Cell viability decreased (2 and 18 h, P < 0.05). PPAR-gamma agonists promoted further apoptosis. In summary, oxidative stress promoted mitochondrial destabilisation in kidney PTE, in association with increased PPAR-gamma phosphorylation. PPAR-gamma agonists failed to protect PTE. Despite positive effects in other tissues, PPAR-gamma activation appears to be detrimental to kidney PTE health when oxidative stress induces damage. PMID- 25122053 TI - Whole exome sequencing implicates an INO80D mutation in a syndrome of aortic hypoplasia, premature atherosclerosis, and arterial stiffness. AB - BACKGROUND: Massively parallel, high-throughput sequencing technology is helping to generate new insights into the genetic basis of human diseases. We used whole exome sequencing to identify the mutation underlying a syndrome affecting 2 siblings with aortic hypoplasia, calcific atherosclerosis, systolic hypertension, and premature cataract. METHODS AND RESULTS: Exonic regions were captured and sequenced using a next-generation sequencing platform to generate 100 bases paired-end reads. A computational genomic data analysis pipeline was used to perform quality control, align reads to a reference genome, and identify genetic variants; findings were confirmed using a different exome analyses pipeline. The 2 siblings were homozygous for a rare missense mutation (Ser818Cys) in INO80D, a subunit of the human INO80 chromatin remodeling complex. Homozygosity mapping and Sanger sequencing confirmed that the mutation is located in one of the runs of homozygosity on chromosome 2. INO80D encodes a key subunit of the human IN080 complex, a multiprotein complex involved in DNA binding, chromatin modification, organization of chromosome structure, and ATP-dependent nucleosome sliding. By introducing a new disulphide-bond in the protein product and also disrupting the composition of low-complexity regions, the Ser818Cys mutation may affect INO80D function, protein-protein interactions, and chromatin remodeling. CONCLUSIONS: Our findings suggest a link between the Ser818Cys mutation in INO80D, a subunit of the human INO80 chromatin remodeling complex, and accelerated arterial aging. PMID- 25122052 TI - Low-expression variant of fatty acid-binding protein 4 favors reduced manifestations of atherosclerotic disease and increased plaque stability. AB - BACKGROUND: Fatty acid-binding protein 4 (FABP4 or aP2 in mice) has been identified as a key regulator of core aspects of cardiometabolic disorders, including lipotoxic endoplasmic reticulum stress in macrophages. A functional promoter polymorphism (rs77878271) of human FABP4 gene has been described resulting in reduced FABP4 transcription. METHODS AND RESULTS: We investigated the effects of this low-expression variant of FABP4 on cardiovascular morbidity and carotid atherosclerosis on a population level (n=7491) and in patient cohorts representing endarterectomized patients with advanced carotid atherosclerosis (n=92) and myocardial infarction (n=3432). We found that the low-expression variant was associated with decreased total cholesterol levels (P=0.006) with the largest reduction in variant allele homozygotes. Obese variant allele carriers also showed reduced carotid intima-media thickness (P=0.010) and lower prevalence of carotid plaques (P=0.060). Consistently, the variant allele homozygotes showed 8-fold lower odds for myocardial infarction (P=0.019; odds ratio, 0.12; 95% confidence interval, 0.003-0.801). Within the carotid plaques, the variant allele was associated with a 3.8-fold reduction in FABP4 transcription (P=0.049) and 2.7 fold reduction in apoptosis (activated caspase 3; P=0.043). Furthermore, the variant allele was enriched to patients with asymptomatic carotid stenosis (P=0.038). High FABP4 expression in the carotid plaques was associated with lipid accumulation, intraplaque hemorrhages, plaque ulcerations, and phosphoactivated endoplasmic reticulum stress markers. CONCLUSIONS: Our results reveal FABP4 rs77878271 as a novel variant affecting serum total cholesterol levels and cardiovascular risk. A therapeutic regimen reducing FABP4 expression within the atherosclerotic plaque may promote lesion stability through modulation of endoplasmic reticulum stress signaling, and attenuation of apoptosis, lipid burden, and inflammation. PMID- 25122056 TI - Nurses' use of an integrated electronic health record: results of a case site analysis. AB - Purpose: To explore how nurses use an integrated Electronic Health Record (EHR) in practice. Methods: A multi-site case study across two hospitals in Kaiser Permanente Northern California. Non-participant observation was used to explore nurses' use of the EHR, while semi-structured interviews with nurses and managers explored their perceptions of the EHR and how it affected their practice. Data were analyzed thematically using codes derived deductively from the literature and inductively from the data. Results: Key themes arising from the analysis suggest that the EHR changed various elements of the way nurses practiced. Introducing the EHR was thought to have improved communication, ease of access to information and the safety of medication administration processes. At an organizational level, there was variability in how the EHR was used to support care documentation and initiatives to improve the quality of care provided by nurses. Conclusion: The EHR was perceived to improve efficiency, safety and communication by the majority of nurses who were interviewed. However, it is likely that a number of other factors such as individual nurse's characteristics and organizational culture influence how an EHR can be used effectively to improve outcomes for patients. PMID- 25122054 TI - Volatilization of arsenic from polluted soil by Pseudomonas putida engineered for expression of the arsM Arsenic(III) S-adenosine methyltransferase gene. AB - Even though arsenic is one of the most widespread environmental carcinogens, methods of remediation are still limited. In this report we demonstrate that a strain of Pseudomonas putida KT2440 endowed with chromosomal expression of the arsM gene encoding the As(III) S-adenosylmethionine (SAM) methyltransfase from Rhodopseudomonas palustris to remove arsenic from contaminated soil. We genetically engineered the P. putida KT2440 with stable expression of an arsM-gfp fusion gene (GE P. putida), which was inserted into the bacterial chromosome. GE P. putida showed high arsenic methylation and volatilization activity. When exposed to 25 MUM arsenite or arsenate overnight, most inorganic arsenic was methylated to the less toxic methylated arsenicals methylarsenate (MAs(V)), dimethylarsenate (DMAs(V)) and trimethylarsine oxide (TMAs(V)O). Of total added arsenic, the species were about 62 +/- 2.2% DMAs(V), 25 +/- 1.4% MAs(V) and 10 +/ 1.2% TMAs(V)O. Volatilized arsenicals were trapped, and the predominant species were dimethylarsine (Me2AsH) (21 +/- 1.0%) and trimethylarsine (TMAs(III)) (10 +/ 1.2%). At later times, more DMAs(V) and volatile species were produced. Volatilization of Me2AsH and TMAs(III) from contaminated soil is thus possible with this genetically engineered bacterium and could be instrumental as an agent for reducing the inorganic arsenic content of soil and agricultural products. PMID- 25122055 TI - Changes in the expression of cyp35a family genes in the soil nematode Caenorhabditis elegans under controlled exposure to chlorpyrifos using passive dosing. AB - In order to use sensitive molecular-level biomarkers for the evaluation of environmental risks, it is necessary to establish a quantitative dose-response relationship. Passive dosing is regarded as a promising new technique for maintaining a constant exposure condition of hydrophobic chemicals in the assay medium. The main goals of the present study were (1) to quantitatively compare gene expression results obtained using the passive dosing method and the conventional spiking method and (2) to investigate changes in gene expression with respect to the free concentration and exposure duration using passive dosing. Chlorpyrifos (CP), which is oxidized by the cytochrome P450 monooxygenases, was selected as a model chemical, and the expression of cytochrome P450 subfamily protein 35A gene series (cyp-35a1-5) was analyzed by quantitative real-time PCR on soil nematode Caenorhabditis elegans. Whereas the free concentration of CP rapidly decreased and the expression of cyp genes varied with the volume of exposure medium and the test duration when the spiking method was used, the free concentration in the assay medium was stable throughout the experiment when the passive dosing method was used. In addition, the level of gene expression increased with exposure time up to 8 h and with increasing CP concentration. The observed increased gene expression could be explained by increasing body residue concentration of CP with exposure time. In conclusion, quantitative dose-response relationships for gene expression biomarkers could be obtained for highly hydrophobic chemicals when the constant exposure condition is provided and the free concentration is used as the dose-metric. PMID- 25122058 TI - Targeted MRSA screening can be as effective as universal screening. PMID- 25122057 TI - Effect of FGF-2 on collagen tissue regeneration by human vertebral bone marrow stem cells. AB - The effects of fibroblast growth factor-2 (FGF-2) on collagen tissue regeneration by human bone marrow stem cells (hBMSCs) were investigated. hBMSCs were isolated from human vertebral body bone marrow during vertebral surgery and a population of hBMSCs with the characteristics of mesenchymal stem cells was observed. The FGF-2 treatment (5 ng/mL) affected on the colony-forming efficiency, proliferation, and in vitro differentiation of hBMSCs. Insoluble/soluble collagen and hydroxyproline synthesis was significantly enhanced in hBMSCs expanded with FGF-2 and the treatment of FGF-2 caused a reduction in the mRNA expression of collagen type I, but an increase of collagen types II and III along with lysyl oxidase family genes. Collagen formation was also examined using an in vivo assay model by transplanting hBMSCs into immunocompromised mice (n=4) and the histologic and immunohistochemical results revealed that significantly more collagen with a well-organized structure was formed by FGF-2-treated hBMSCs at 8 weeks posttransplantation (P<0.05). The DNA microarray assay demonstrated that genes related to extracellular matrix formation were significantly upregulated. To elucidate the underlying mechanism, chemical inhibitors against extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) were treated and following downstream expression was observed. Collectively, FGF-2 facilitated the collagen-producing potency of hBMSCs both in vitro and in vivo, rendering them more suitable for use in collagen regeneration in the clinical field. PMID- 25122060 TI - Dramatic changes in 67 miRNAs during initiation of first wave of spermatogenesis in Mus musculus testis: global regulatory insights generated by miRNA-mRNA network analysis. AB - We mapped global changes in miRNA and mRNA profiles spanning the first wave of spermatogenesis using prepubertal (Postnatal Day 8 [P8]), pubertal (P16), and adolescent (P24) Mus musculus testes and identified the differential expression of 67 miRNAs and 8226 mRNAs. These two data sets were integrated into miRNA dependent regulatory networks based on miRWalk predictions. In a network representing the P8 to P16 transition, downregulation of four miRNAs and upregulation of 19 miRNAs were linked with 81 upregulated target mRNAs and 228 downregulated target mRNAs, respectively. Furthermore, during the P16 to P24 transition, two miRNAs were downregulated, and eight miRNAs were upregulated, which linked with 64 upregulated mRNAs and 389 downregulated mRNAs, respectively. Only three of the miRNAs present in the network (miR-34b-5p, miR-34c, and miR 449a) showed a progressive increase from P8 through P16 to P24, while the remaining miRNAs in the network showed statistically significant changes in their levels either during the P8 to P16 transition or during the P16 to P24 transition. Analysis of the chromosomal location of these differentially expressed miRNAs showed that 14 out of 25 miRNAs upregulated from P8 to P16, and 18 out of 40 miRNAs upregulated from P8 to P24 were X-linked. This is suggestive of their escape from meiotic sex chromosome inactivation and postmeiotic sex chromatin. This integrated network of miRNA-level and mRNA-level changes in mouse testis during the first wave of spermatogenesis is expected to build a base for evaluating the role of miRNA-mediated gene expression regulation in maturing mammalian testis. PMID- 25122061 TI - Trophoblast-specific reduction of VEGFA alters placental gene expression and maternal cardiovascular function in mice. AB - Given the angiogenic function of vascular endothelial growth factor A (VEGFA), the function of its expression by trophoblast in the avascular placental junctional zone is unknown. In mice, cells from the trophoblast-specific protein alpha (Tpbpa) lineage populate this zone and, in late gestation, some of these cells invade the decidual layer. To diminish Vegfa expression in Tpbpa cells, we crossed Vegfa(flox/flox) females with males carrying Tpbpa-Cre. For single deletion (sd) of Vegfa in Tpbpa cells in 100% of conceptuses (SD100 pregnancies, sd conceptuses) we crossed homozygous lines. For double deletion (dd) of both Vegfa alleles in 50% of the conceptuses (DD50 pregnancies, 50% dd conceptuses and 50% no deletion [nd]), we crossed homozygous Vegfa(flox/flox) females with males heterozygous for Tpbpa-Cre and homozygous for Vegfa(flox/flox). Controls were Vegfa(flox/flox) females bred to wild-type males (V-CTRL pregnancies). In SD100 pregnancies, maternal plasma immunoreactive VEGFA significantly increased and arterial blood pressure decreased, whereas fetal body weight and placental Flt1, sFlt1, and Prl3b1 mRNA were unchanged. In DD50, maternal immunoreactive VEGFA and arterial pressures were unaltered, but both dd and nd conceptuses exhibited significantly increased embryonic lethality, altered expression of Flt1, sFlt1, and Prl3b1 mRNA in the decidual layer, and decreased fetal body weight relative to V-CTRL. Maternal cardiac output significantly increased in proportion to dd conceptuses in the pregnancy. In DD50, results are consistent with altered maternal function beginning in early gestation and adversely impacting both conceptus genotypes. We conclude that maternal function is influenced by Vegfa expression in trophoblast cells at the maternal-fetal interface, likely via an endocrine mechanism. PMID- 25122062 TI - MicroRNA-378a-5p targets cyclin G2 to inhibit fusion and differentiation in BeWo cells. AB - MicroRNAs are expressed abundantly in the placenta throughout pregnancy. We have previously reported that microRNA (miR)-378a-5p promoted trophoblast migration and invasion. To further understand the role of miR-378a-5p during placental development, we investigated whether it may regulate the differentiation of syncytiotrophoblast (STB). Using a choriocarcinoma cell line, BeWo, we found that miR-378a-5p was down-regulated during forskolin-induced STB differentiation. Transfection of a miR-378a-5p mimic into BeWo cells decreased the formation of multinucleated STB, increased E-cadherin, and decreased the expression level of STB marker genes. On the other hand, transfection of anti-miR-378a-5p resulted in an increase in formation of multinucleated STB and expression of STB marker genes, as well as the loss of E-cadherin. Bioinformatic analysis revealed that miR-378a-5p has four potential binding sites at the 3' untranslated region (UTR) of cyclin G2 (CCNG2). Using luciferase reporter assays, we showed that miR-378a 5p decreased the luciferase activity of reporter constructs that contain CCNG2 3' UTR. In addition, miR-378a-5p decreased, whereas anti-miR-378a-5p increased, CCNG2 mRNA levels. Overexpression of CCNG2 increased the expression of syncytin-1 and fusion index and reversed the inhibitory effects of miR-378a-5p. In contrast, silencing of CCNG2 using siRNA increased E-cadherin and decreased syncytin-1 levels. These findings provide initial evidence that CCNG2 promotes STB differentiation and suggest that miR-378a-5p exerts an inhibitory role in STB differentiation, in part, by down-regulating CCNG2 expression, in the BeWo cell model. PMID- 25122063 TI - Endocrine gland-derived endothelial growth factor (EG-VEGF) is a potential novel regulator of human parturition. AB - EG-VEGF is an angiogenic factor that we identified as a new placental growth factor during human pregnancy. EG-VEGF is also expressed in the mouse fetal membrane (FM) by the end of gestation, suggesting a local role for this protein in the mechanism of parturition. However, injection of EG-VEGF to gravid mice did not induce labor, suggesting a different role for EG-VEGF in parturition. Here, we searched for its role in the FM in relation to human parturition. Human pregnant sera and total FM, chorion, and amnion were collected during the second and third trimesters from preterm no labor, term no labor, and term labor patients. Primary human chorion trophoblast and FM explants cultures were also used. We demonstrate that circulating EG-VEGF increased toward term and significantly decreased at the time of labor. EG-VEGF production was higher in the FM compared to placentas matched for gestational age. Within the FM, the chorion was the main source of EG-VEGF. EG-VEGF receptors, PROKR1 and PROKR2, were differentially expressed within the FM with increased expression toward term and an abrupt decrease with the onset of labor. In chorion trophoblast and FM explants collected from nonlaboring patients, EG-VEGF decreased metalloproteinase 2 and -9 activities and increased PGDH (prostaglandin-metabolizing enzyme) expression. Altogether these data demonstrate that EG-VEGF is a new cytokine that acts locally to ensure FM protection in late pregnancy. Its fine contribution to the initiation of human labor is exhibited by the abrupt decrease in its levels as well as a reduction in its receptors. PMID- 25122064 TI - The role of placental nutrient sensing in maternal-fetal resource allocation. AB - The placenta mediates maternal-fetal exchange and has historically been regarded as a passive conduit for nutrients. However, emerging evidence suggests that the placenta actively responds to nutritional and metabolic signals from the mother and the fetus. We propose that the placenta integrates a multitude of maternal and fetal nutritional cues with information from intrinsic nutrient-sensing signaling pathways to match fetal demand with maternal supply by regulating maternal physiology, placental growth, and nutrient transport. This process, which we have called placental nutrient sensing, ensures optimal allocation of resources between the mother and the fetus to maximize the chances for propagation of parental genes without jeopardizing maternal health. We suggest that these mechanisms have evolved because of the evolutionary pressures of maternal undernutrition, which result in decreased placental growth and down regulation of nutrient transporters, thereby limiting fetal growth to ensure maternal survival. These regulatory loops may also function in response to maternal overnutrition, leading to increased placental growth and nutrient transport in cases of maternal obesity or gestational diabetes. Thus, placental nutrient sensing modulates maternal-fetal resource allocation to increase the likelihood of reproductive success. This model implies that the placenta plays a critical role in mediating fetal programming and determining lifelong health. PMID- 25122066 TI - Synergistic simvastatin and metformin combination chemotherapy for osseous metastatic castration-resistant prostate cancer. AB - Docetaxel chemotherapy remains a standard of care for metastatic castration resistant prostate cancer (CRPC). Docetaxel modestly increases survival, yet results in frequent occurrence of side effects and resistant disease. An alternate chemotherapy with greater efficacy and minimal side effects is needed. Acquisition of metabolic aberrations promoting increased survival and metastasis in CRPC cells includes constitutive activation of Akt, loss of adenosine monophosphate-activated protein kinase (AMPK) activity due to Ser-485/491 phosphorylation, and overexpression of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMG-CoAR). We report that combination of simvastatin and metformin, within pharmacologic dose range (500 nmol/L to 4 MUmol/L simvastatin and 250 MUmol/L to 2 mmol/L metformin), significantly and synergistically reduces C4 2B3/B4 CRPC cell viability and metastatic properties, with minimal adverse effects on normal prostate epithelial cells. Combination of simvastatin and metformin decreased Akt Ser-473 and Thr-308 phosphorylation and AMPKalpha Ser 485/491 phosphorylation; increased Thr-172 phosphorylation and AMPKalpha activity, as assessed by increased Ser-79 and Ser-872 phosphorylation of acetyl CoA carboxylase and HMG-CoAR, respectively; decreased HMG-CoAR activity; and reduced total cellular cholesterol and its synthesis in both cell lines. Studies of C4-2B4 orthotopic NCr-nu/nu mice further demonstrated that combination of simvastatin and metformin (3.5-7.0 MUg/g body weight simvastatin and 175-350 MUg/g body weight metformin) daily by oral gavage over a 9-week period significantly inhibited primary ventral prostate tumor formation, cachexia, bone metastasis, and biochemical failure more effectively than 24 MUg/g body weight docetaxel intraperitoneally injected every 3 weeks, 7.0 MUg/g/day simvastatin, or 350 MUg/g/day metformin treatment alone, with significantly less toxicity and mortality than docetaxel, establishing combination of simvastatin and metformin as a promising chemotherapeutic alternative for metastatic CRPC. PMID- 25122067 TI - The CDK4/6 inhibitor LY2835219 overcomes vemurafenib resistance resulting from MAPK reactivation and cyclin D1 upregulation. AB - B-RAF selective inhibitors, including vemurafenib, were recently developed as effective therapies for melanoma patients with B-RAF V600E mutation. However, most patients treated with vemurafenib eventually develop resistance largely due to reactivation of MAPK signaling. Inhibitors of MAPK signaling, including MEK1/2 inhibitor trametinib, failed to show significant clinical benefit in patients with acquired resistance to vemurafenib. Here, we describe that cell lines with acquired resistance to vemurafenib show reactivation of MAPK signaling and upregulation of cyclin D1 and are sensitive to inhibition of LY2835219, a selective inhibitor of cyclin-dependent kinase (CDK) 4/6. LY2835219 was demonstrated to inhibit growth of melanoma A375 tumor xenografts and delay tumor recurrence in combination with vemurafenib. Furthermore, we developed an in vivo vemurafenib-resistant model by continuous administration of vemurafenib in A375 xenografts. Consistently, we found that MAPK is reactivated and cyclin D1 is elevated in vemurafenib-resistant tumors, as well as in the resistant cell lines derived from these tumors. Importantly, LY2835219 exhibited tumor growth regression in a vemurafenib-resistant model. Mechanistic analysis revealed that LY2835219 induced apoptotic cell death in a concentration-dependent manner in vemurafenib-resistant cells whereas it primarily mediated cell-cycle G1 arrest in the parental cells. Similarly, RNAi-mediated knockdown of cyclin D1 induced significantly higher rate of apoptosis in the resistant cells than in parental cells, suggesting that elevated cyclin D1 activity is important for the survival of vemurafenib-resistant cells. Altogether, we propose that targeting cyclin D1 CDK4/6 signaling by LY2835219 is an effective strategy to overcome MAPK-mediated resistance to B-RAF inhibitors in B-RAF V600E melanoma. PMID- 25122065 TI - Genetic alterations affecting cholesterol metabolism and human fertility. AB - Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. PMID- 25122068 TI - Integrated analysis of transcriptomes of cancer cell lines and patient samples reveals STK11/LKB1-driven regulation of cAMP phosphodiesterase-4D. AB - The recent proliferation of data on large collections of well-characterized cancer cell lines linked to therapeutic drug responses has made it possible to identify lineage- and mutation-specific transcriptional markers that can help optimize implementation of anticancer agents. Here, we leverage these resources to systematically investigate the presence of mutation-specific transcription markers in a wide variety of cancer lineages and genotypes. Sensitivity and specificity of potential transcriptional biomarkers were simultaneously analyzed in 19 cell lineages grouped into 228 categories based on the mutational genotypes of 12 cancer-related genes. Among a total of 1,455 category-specific expression patterns, the expression of cAMP phosphodiesterase-4D (PDE4D) with 11 isoforms, one of the PDE4(A-D) subfamilies, was predicted to be regulated by a mutant form of serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) present in lung cancer. STK11/LKB1 is the primary upstream kinase of adenine monophosphate activated protein kinase (AMPK). Subsequently, we found that the knockdown of PDE4D gene expression inhibited proliferation of STK11-mutated lung cancer lines. Furthermore, challenge with a panel of PDE4-specific inhibitors was shown to selectively reduce the growth of STK11-mutated lung cancer lines. Thus, we show that multidimensional analysis of a well-characterized large-scale panel of cancer cell lines provides unprecedented opportunities for the identification of unexpected oncogenic mechanisms and mutation-specific drug targets. PMID- 25122070 TI - Prostate cancer cell response to paclitaxel is affected by abnormally expressed securin PTTG1. AB - PTTG1 protein, the human securin, has a central role in sister chromatid separation during mitosis, and its altered expression has been reported in many tumor types. Paclitaxel is a widely used chemotherapeutic drug, whose mechanism of action is related to its ability to arrest cells in mitosis and the subsequent induction of the intrinsic apoptotic pathway. By using two prostate cancer cell lines with different responses to paclitaxel treatment, we have identified two situations in which PTTG1 influences cell fate differentially. In slippage-prone PC3 cells, both PTTG1 downregulation and overexpression induce an increase in mitotic cells that is associated with diminished apoptosis after paclitaxel treatment. In LNCaP cells, however, PTTG1 downregulation prevents mitotic entry and, subsequently, inhibits mitosis-associated, paclitaxel-induced apoptosis. In contrast, PTTG1 overexpression induces an increase in mitotic cells and apoptosis after paclitaxel treatment. We have also identified a role for Mcl-1 protein in preventing apoptosis during mitosis in PC3 cells, as simultaneous PTTG1 and Mcl-1 silencing enhances mitosis-associated apoptosis after paclitaxel treatment. The finding that a more efficient mitotic arrest alone in PC3 cells is not enough to increase apoptosis was also confirmed with the observation that a selected paclitaxel-resistant PC3 cell line showed an apoptosis-resistant phenotype associated with increased mitosis upon paclitaxel treatment. These findings could contribute to identify putative responsive and nonresponsive cells and help us to approach incomplete responses to paclitaxel in the clinical setting. PMID- 25122072 TI - In vitro selection, characterization, and biosensing application of high-affinity cylindrospermopsin-targeting aptamers. AB - Contamination of freshwater with cyanotoxin cylindrospermopsin (CYN) represents a significant global concern for public health. The sensitive detection of CYN is necessary to effectively manage and control the treatment of water resources. Here we report a novel, highly sensitive label-free aptasensor for CYN analysis, using aptamers as specific receptors. We have selected the DNA aptamers from a diverse random library using the in vitro screening SELEX approach. The aptamers exhibited high affinity for CYN with Kd of nanomolar range. One aptamer exhibited conformational change upon CYN recognition (CD analysis) and was used to fabricate the label-free impedimetric aptasensor for CYN. A self-assembled monolayer from a disulfide-derivatized aptamer was formed on a gold electrode to fabricate the aptasensor. Upon CYN capturing to the aptasensor surface, a marked drop in the electron transfer resistance was obtained, which was used as the principle of detection of CYN. This resulted from the aptamer's conformational change induced by CYN recognition. The present aptasensor could detect CYN with the limit of detection as low as 100 pM and a wide linear range of 0.1 to 80 nM. When mounted on the gold surface, the aptamer exhibited a lower dissociation constant for CYN than that observed in the fluorescence assay, implying that the anchoring of the aptamer on the Au surface improved its affinity to CYN. Moreover, the aptasensor showed high specificity toward other coexistent cyanobacterial toxins of microcystin-LR and Anatoxin-a. Further biosensor designs will be generated using those aptamers for simple and sensitive CYN monitoring. PMID- 25122074 TI - Fully solution-processed transparent conducting oxide-free counter electrodes for dye-sensitized solar cells: spray-coated single-wall carbon nanotube thin films loaded with chemically-reduced platinum nanoparticles. AB - We report fully solution-processed fabrication of transparent conducting oxide free counter electrodes (CEs) for dye-sensitized solar cells (DSSCs) by combining spray-coating of single-wall carbon nanotubes (SWCNTs) and chemical reduction of chloroplatinic acid precursor to platinum nanoparticles (Pt NPs) with formic acid. The power conversion efficiency of a semitransparent DSSC with such SWCNT based CE loaded with Pt NPs is comparable to that of a control device with a conventional CE. Quantification of Pt loading shows that network morphology of entangled SWCNTs is efficient in forming and retaining chemically reduced Pt NPs. Moreover, electron microscopy and electrochemical impedance spectroscopy results show that mainly Pt NPs, which are tens of nanometers in diameter and reside at the surface of SWCNT CEs, contribute to electrocatalytic activity for triiodide reduction, to which we attribute strong correlation between power conversion efficiency of DSSCs and time constant deduced from equivalent-circuit analysis of impedance spectra. PMID- 25122069 TI - Drug repurposing identifies a synergistic combination therapy with imatinib mesylate for gastrointestinal stromal tumor. AB - Gastrointestinal stromal tumor (GIST) is a rare and therefore often neglected disease. Introduction of the kinase inhibitor imatinib mesylate radically improved the clinical response of patients with GIST; however, its effects are often short-lived, with GISTs demonstrating a median time-to-progression of approximately two years. Although many investigational drugs, approved first for other cancers, have been subsequently evaluated for the management of GIST, few have greatly affected the overall survival of patients with advanced disease. We employed a novel, focused, drug-repurposing effort for GIST, including imatinib mesylate-resistant GIST, evaluating a large library of FDA-approved drugs regardless of current indication. As a result of the drug-repurposing screen, we identified eight FDA-approved drugs, including fludarabine phosphate (F-AMP), that showed synergy with and/or overcame resistance to imatinib mesylate. F-AMP induces DNA damage, Annexin V, and caspase-3/7 activities as the cytotoxic effects on GIST cells, including imatinib mesylate-resistant GIST cells. F-AMP and imatinib mesylate combination treatment showed greater inhibition of GIST cell proliferation when compared with imatinib mesylate and F-AMP alone. Successful in vivo experiments confirmed the combination of imatinib mesylate with F-AMP enhanced the antitumor effects compared with imatinib mesylate alone. Our results identified F-AMP as a promising, repurposed drug therapy for the treatment of GISTs, with potential to be administered in combination with imatinib mesylate or for treatment of imatinib mesylate-refractory tumors. PMID- 25122073 TI - Anal heterosex among young people and implications for health promotion: a qualitative study in the UK. AB - OBJECTIVE: To explore expectations, experiences and circumstances of anal sex among young people. DESIGN: Qualitative, longitudinal study using individual and group interviews. PARTICIPANTS: 130 men and women aged 16-18 from diverse social backgrounds. SETTING: 3 contrasting sites in England (London, a northern industrial city, rural southwest). RESULTS: Anal heterosex often appeared to be painful, risky and coercive, particularly for women. Interviewees frequently cited pornography as the 'explanation' for anal sex, yet their accounts revealed a complex context with availability of pornography being only one element. Other key elements included competition between men; the claim that 'people must like it if they do it' (made alongside the seemingly contradictory expectation that it will be painful for women); and, crucially, normalisation of coercion and 'accidental' penetration. It seemed that men were expected to persuade or coerce reluctant partners. CONCLUSIONS: Young people's narratives normalised coercive, painful and unsafe anal heterosex. This study suggests an urgent need for harm reduction efforts targeting anal sex to help encourage discussion about mutuality and consent, reduce risky and painful techniques and challenge views that normalise coercion. PMID- 25122071 TI - Lipid catabolism via CPT1 as a therapeutic target for prostate cancer. AB - Prostate cancer is the most commonly diagnosed malignancy among Western men and accounts for the second leading cause of cancer-related deaths. Prostate cancer tends to grow slowly and recent studies suggest that it relies on lipid fuel more than on aerobic glycolysis. However, the biochemical mechanisms governing the relationships between lipid synthesis, lipid utilization, and cancer growth remain unknown. To address the role of lipid metabolism in prostate cancer, we have used etomoxir and orlistat, clinically safe drugs that block lipid oxidation and lipid synthesis/lipolysis, respectively. Etomoxir is an irreversible inhibitor of the carnitine palmitoyltransferase (CPT1) enzyme that decreases beta oxidation in the mitochondria. Combinatorial treatments using etomoxir and orlistat resulted in synergistic decreased viability in LNCaP, VCaP, and patient derived benign and prostate cancer cells. These effects were associated with decreased androgen receptor expression, decreased mTOR signaling, and increased caspase-3 activation. Knockdown of CPT1A enzyme in LNCaP cells resulted in decreased palmitate oxidation but increased sensitivity to etomoxir, with inactivation of AKT kinase and activation of caspase-3. Systemic treatment with etomoxir in nude mice resulted in decreased xenograft growth over 21 days, underscoring the therapeutic potential of blocking lipid catabolism to decrease prostate cancer tumor growth. PMID- 25122076 TI - Limitation of activity due to chronic conditions United States, 1969 and 1970. AB - During 1969 and 1970 an estimated average of 23,237,000 persons, about 11.7 percent of the civilian, noninstitutionalized population of the United States, were reported in health interviews to be limited to some extent as a result of chronic disease or impairment. Limitation of activity is a measure of long-term disability resulting from chronic conditions. It is defined as inability to carry on the major activity for one's age-sex group, such as working, keeping house, or going to school; restriction in the amount or kind of major activity; or restriction in relation to other activities, such as recreational, church, or civic interests. PMID- 25122075 TI - Noise-assisted charge pump in elastically deformable molecular junctions. AB - We study a charge pump realized with an elastically deformable quantum dot whose center of mass follows a nonlinear stochastic dynamics. The interplay of noise, nonlinear effects, dissipation and interaction with an external time-dependent driving on the pumped charge is fully analyzed. The results show that the quantum pumping mechanism not only is not destroyed by the force fluctuations, but it becomes stronger when the forcing signal frequency is tuned close to the resonance of the vibrational mode. The robustness of the quantum pump with temperature is also investigated and an exponential decay of the pumped charge is found when the coupling to the vibrational mode is present. Implications of our results for nanoelectromechanical systems are also discussed. PMID- 25122077 TI - Septic arthritis and acute rheumatic fever in children: the diagnostic value of serological inflammatory markers. AB - INTRODUCTION: Joint pain and raised inflammatory markers are features of both acute rheumatic fever (ARF) and septic arthritis, often posing a diagnostic challenge to clinicians. Important differences in the presenting serological inflammatory marker profile may assist patient diagnosis, however, as clinical experience suggests that ARF is associated with a higher erythrocyte sedimentation rate (ESR), whereas other serological markers may be similarly elevated in these 2 conditions. OBJECTIVE: The goal of this study was to determine the diagnostic value of serological inflammatory markers and white cell count (WCC) in children presenting with acute joint pain secondary to ARF or septic arthritis. METHODS: Data were obtained from the Auckland regional rheumatic fever database and hospital computer records between 2005 and 2012. Records of all patients under the age of 16 years who were admitted with a new diagnosis of ARF or septic arthritis were analyzed. The diagnosis of ARF was defined on the basis of the New Zealand modification of the Jones Criteria, and the diagnosis of septic arthritis was defined on the basis of joint fluid cytology and culture. Baseline characteristics, serological inflammatory markers, and serum WCC were compared between the ARF and septic arthritis patient groups. RESULTS: Children with ARF displayed significantly higher ESR, higher serum C reactive protein, and lower serum WCC than children with septic arthritis on presentation to hospital. In children presenting with monoarthritis, an ESR>64.5, serum WCC<12.1*109/L, and age above 8.5 years were found to be significant independent predictors of ARF. Children with all 3 predictors had a 71% risk for ARF and a 29% risk for septic arthritis. A significant proportion (30%) of children with the final diagnosis of ARF initially presented with monoarthritis; 14% of these children (5/34) had received nonsteroidal anti-inflammatory medication before hospital presentation, and 74% of these children (25/34) had abnormal echocardiograms on admission. CONCLUSIONS: ARF and septic arthritis are important diagnoses to consider in children presenting with acute joint pain in New Zealand. A significant proportion of patients with ARF initially present with acute monoarthritis. Serological inflammatory markers and WCC on presentation differ significantly between children with ARF and septic arthritis. PMID- 25122079 TI - Comment on Morin et al "Positive Communication Paradigm Decreases Early Recurrence in Clubfoot Treatment". PMID- 25122078 TI - Congenital tibial deficiency: a 37-year experience at 1 institution. AB - BACKGROUND: The purpose of this study is to evaluate all cases of tibial deficiency seen at a single institution from 1975 to 2012, to classify these cases by the Jones classification if possible, to evaluate for associated anomalies, and to review the surgical treatments provided to these patients. METHODS: Ninety-five patients (125 extremities) treated at our institution between 1975 and 2012 with tibial deficiency had complete records allowing for classification and review of full treatment course. These patients' records and imaging were retrospectively reviewed for any associated anomalies, surgical treatment performed, and limb deformity characterized by the Jones classification where possible. RESULTS: Seventy-three of 125 limbs (58%) were classified as Jones type 1A, 6 (5%) as type 1B, 18 (14%) as type 2, and 12 (10%) as type 4. Two limbs initially classified radiographically as type 3 deformities subsequently developed a proximal tibia epiphyses and thus did not represent true type 3 deformities. Fourteen limbs (11%) were characterized by global tibial deficiency but with proximal and distal epiphyses and could not be classified according to the Jones classification. Seventy-five of the 95 patients (79%) had associated anomalies. Other lower extremity anomalies were most frequent; however, upper extremity, spine, and visceral anomalies were also noted. CONCLUSIONS: True type 3 deformity as described by Jones was not seen in our patient population; all patients developed a proximal epiphysis. Therefore, this group may be better served by limb salvage than amputation. Fourteen (11%) limbs, characterized by global tibia shortening relative to the fibula of variable degree, could not be classified according to the Jones classification. We propose adding this group as a new group within the Jones classification, which we call type 5. Finally, in this patient population, the Brown procedure for type 1 tibial deficiency universally failed, confirming results of prior studies. LEVEL OF EVIDENCE: This is a level IV study, a retrospective review of 95 patients with tibial deficiency from a single institution. PMID- 25122080 TI - Calf circumference discrepancies in patients with unilateral clubfoot: Ponseti versus surgical release. AB - BACKGROUND: Talipes equinovarus is the most common congenital lower limb abnormality. Decreased calf size has been found to have negative impacts on patients' subjective appraisals of long-term outcomes. This study compares calf circumference ratios in 2 groups of patients with unilateral clubfoot, those treated according to the Ponseti method and those treated with extensive surgery, to determine whether the current standard of care achieves better anatomic outcomes. METHODS: Patients >1 year after treatment for unilateral clubfoot were recruited during normal follow-up appointments and both calves were measured using a standardized protocol. A questionnaire concerning their treatment history was also completed. Data were analyzed by comparing calf circumference ratios between treatment modalities. RESULTS: Thirty-five patients with unilateral clubfoot were recruited after satisfying inclusion criteria. Twenty-four (69%) were included in the Ponseti-managed group, and 11 (31%) were in the extensive surgery group. The affected legs were on average 3% to 10% smaller than the control legs across all groups. The surgery group's average calf ratio was significantly less at 90.8%+/-3.5% compared with 94.4%+/-3.3% in the Ponseti group. CONCLUSIONS: The calf circumference of limbs affected by clubfoot is significantly smaller in those treated with extensive surgery as compared with those treated with the Ponseti method alone, with or without percutaneous tenotomy. This supports the Ponseti method as the standard of care for achieving the most favorable anatomic outcome. LEVEL OF EVIDENCE: Level I. PMID- 25122081 TI - What's new in Shock? September 2014. PMID- 25122083 TI - Impact of arterial oxygen tension on venous oxygen saturation. PMID- 25122082 TI - Remote ischemic preconditioning mitigates myocardial and neurological dysfunction via K(ATP) channel activation in a rat model of hemorrhagic shock. AB - Severe hemorrhagic shock and resuscitation is a state of global body ischemia and reperfusion that causes myocardial and cerebral dysfunction. We investigated whether remote ischemic preconditioning (RIPC) would reduce myocardial and cerebral ischemia and reperfusion injuries after hemorrhagic shock as the result of the K(ATP) channel activation. Twenty-one male rats were randomized into three groups: RIPC, RIPC with K(ATP) channel blocker, and control. Remote ischemic preconditioning was induced by four cycles of 5 min of limb ischemia followed by reperfusion for 5 min. Hemorrhagic shock was induced by removing 50% of the estimated total blood volume during an interval of 1 h. Thirty minutes after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The animals were monitored for 2 h and observed for an additional 72 h. Myocardial function was measured by echocardiography, and sublingual microcirculation was measured by a sidestream dark-field imaging device at baseline, 1 h after bleeding, 30 min after the completion of bleeding, 30 min after reinfusion, and hourly intervals thereafter. The survival and neurological function were evaluated at 12, 24, 48, and 72 h after reinfusion. At 2 h after reinfusion, ejection fraction and myocardial performance index were significantly better in the RIPC group than in the control group (P < 0.01). The sublingual microvascular flow index and perfused vessel density were significantly greater after reinfusion in the RIPC group than that in the control group (P < 0.01). The duration of survival was significantly longer, and neurological deficit score was significantly better in the RIPC group than the control animals (P < 0.01). Pretreatment with the K(ATP) channel blocker (glibenclamide) completely abolished the myocardial and cerebral protective effects of RIPC. We demonstrate, for the first time, that after severe hemorrhagic shock and resuscitation, RIPC mitigated myocardial and neurological dysfunction with improved survival by activation of the K(ATP) channel. PMID- 25122084 TI - Reply: To PMID 24667613. PMID- 25122085 TI - X-ray scattering from immunostimulatory tetrapod-shaped DNA in aqueous solution to explore its biological activity-conformation relationship. AB - We carried out synchrotron X-ray scattering experiments from four DNA supermolecules designed to form tetrapod shapes; these supermolecules had different sequences but identical numbers of total base pairs, and each contained an immunostimulatory CpG motif. We confirmed that the supermolecules did indeed form the expected tetrapod shape. The sample that had the largest radius of gyration (Rg) induced the most cytokine secretion from cultured immune cells. Structural analysis in combination with a rigid tetrapod model and an atomic scale DNA model revealed that the larger Rg can be ascribed to dissociation of the DNA double strands in the central connecting portion of the DNA tetrapod. This finding suggests that the biological activity is related to the ease with which single DNA strands can be formed. PMID- 25122087 TI - Antioxidants and respiratory disease: the uric acid paradox. PMID- 25122086 TI - Epigenetic landscapes explain partially reprogrammed cells and identify key reprogramming genes. AB - A common metaphor for describing development is a rugged "epigenetic landscape" where cell fates are represented as attracting valleys resulting from a complex regulatory network. Here, we introduce a framework for explicitly constructing epigenetic landscapes that combines genomic data with techniques from spin-glass physics. Each cell fate is a dynamic attractor, yet cells can change fate in response to external signals. Our model suggests that partially reprogrammed cells are a natural consequence of high-dimensional landscapes, and predicts that partially reprogrammed cells should be hybrids that co-express genes from multiple cell fates. We verify this prediction by reanalyzing existing datasets. Our model reproduces known reprogramming protocols and identifies candidate transcription factors for reprogramming to novel cell fates, suggesting epigenetic landscapes are a powerful paradigm for understanding cellular identity. PMID- 25122088 TI - Response to: Domiciliary long term non-invasive ventilation in COPD: should we select subgroups with a better likelihood to respond to NIV in subsequent randomised controlled trials? PMID- 25122089 TI - Spinosad and the tomato borer Tuta absoluta: a bioinsecticide, an invasive pest threat, and high insecticide resistance. AB - The introduction of an agricultural pest species into a new environment is a potential threat to agroecosystems of the invaded area. The phytosanitary concern is even greater if the introduced pest's phenotype expresses traits that will impair the management of that species. The invasive tomato borer, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is one such species and the characterization of the insecticide resistance prevailing in the area of origin is important to guide management efforts in new areas of introduction. The spinosad is one the main insecticides currently used in Brazil for control of the tomato borer; Brazil is the likely source of the introduction of the tomato borer into Europe. For this reason, spinosad resistance in Brazilian populations of this species was characterized. Spinosad resistance has been reported in Brazilian field populations of this pest species, and one resistant population that was used in this study was subjected to an additional seven generations of selection for spinosad resistance reaching levels over 180,000-fold. Inheritance studies indicated that spinosad resistance is monogenic, incompletely recessive and autosomal with high heritability (h(2) = 0.71). Spinosad resistance was unstable without selection pressure with a negative rate of change in the resistance level ( = -0.51) indicating an associated adaptive cost. Esterases and cytochrome P450-dependent monooxygenases titration decreased with spinosad selection, indicating that these detoxification enzymes are not the underlying resistance mechanism. Furthermore, the cross-resistance spectrum was restricted to the insecticide spinetoram, another spinosyn, suggesting that altered target site may be the mechanism involved. Therefore, the suspension of spinosyn use against the tomato borer would be a useful component in spinosad resistance management for this species. Spinosad use against this species in introduced areas should be carefully monitored to prevent rapid selection of high levels of resistance and the potential for its spread to new areas. PMID- 25122091 TI - A life-course approach to human reproduction. PMID- 25122092 TI - Griefwork online: perinatal loss, lifecourse disruption and online support. AB - The Internet provides new opportunities for accessing and giving support following perinatal loss and in this article we report on a project concerned to explore the use of social networking and online networks following such an experience. Perinatal loss can be defined and perceived as biographical disruption yet this type of loss sometimes lacks social recognition. Our ethnographic study reveals that not only do mothers, and sometimes fathers and grandmothers, seek support on the Internet but they also engage in griefwork (the work the bereaved do with others). PMID- 25122090 TI - EVA-1 functions as an UNC-40 Co-receptor to enhance attraction to the MADD-4 guidance cue in Caenorhabditis elegans. AB - We recently discovered a secreted and diffusible midline cue called MADD-4 (an ADAMTSL) that guides migrations along the dorsoventral axis of the nematode Caenorhabditis elegans. We showed that the transmembrane receptor, UNC-40 (DCC), whose canonical ligand is the UNC-6 (netrin) guidance cue, is required for extension towards MADD-4. Here, we demonstrate that MADD-4 interacts with an EVA 1/UNC-40 co-receptor complex to attract cell extensions. EVA-1 is a conserved transmembrane protein with predicted galactose-binding lectin domains. EVA-1 functions in the same pathway as MADD-4, physically interacts with both MADD-4 and UNC-40, and enhances UNC-40's sensitivity to the MADD-4 cue. This enhancement is especially important in the presence of UNC-6. In EVA-1's absence, UNC-6 interferes with UNC-40's responsiveness to MADD-4; in UNC-6's absence, UNC-40's responsiveness to MADD-4 is less dependent on EVA-1. By enabling UNC-40 to respond to MADD-4 in the presence of UNC-6, EVA-1 may increase the precision by which UNC-40-directed processes can reach their MADD-4-expressing targets within a field of the UNC-6 guidance cue. PMID- 25122093 TI - Sex differences in predicting chronicity of low-back pain after acute trauma using lumbar muscle area. AB - OBJECTIVE: The aim of this study was to investigate sex differences in predicting chronicity of low-back pain after acute trauma using cross-sectional areas of paraspinal (multifidus and erector spinae) and psoas muscles. DESIGN: Between January 2006 and December 2010, a total of 54 patients were interviewed at least 6 mos after the trauma event. The subjects were classified into chronic low-back pain group and improved low-back pain group according to the presence of low-back pain for more than 6 mos. The cross-sectional area of the multifidus, erector spinae, and psoas muscles was measured at the level of the lower margin of the L3 and L5 vertebrae using magnetic resonance imaging. RESULTS: The cross-sectional area of the multifidus and erector spinae muscles at L5 in the chronic low-back pain group was significantly smaller than that of the improved low-back pain group (P < 0.05) in the men. There were no significant differences in the other parameters between the groups in the men. There were no significant differences in any parameters in the women. CONCLUSIONS: In the men, the cross-sectional area of the multifidus and erector spinae muscles at the lower lumbar level can be considered to be prognostic factors for the chronic low-back pain after acute trauma. The authors thus suggest that strengthening of lumbar paraspinal muscles could be helpful for preventing chronicity of low-back pain. PMID- 25122094 TI - Men with early degrees of knee osteoarthritis present functional and morphological impairments of the quadriceps femoris muscle. AB - OBJECTIVE: Quadriceps muscle weakness is common in knee osteoarthritis (OA). Reasons for weakness may include atrophy, reduction in the muscle fibers number, and changes in the muscle activation. It is uncertain when these muscular changes begin to appear. Therefore, the purpose of this study was to determine whether men with early stages of knee OA already had functional and quadriceps muscle morphologic alterations. DESIGN: Forty men were divided into two groups: control group (healthy subjects) and OA group (subjects with knee OA). A biopsy of the vastus lateralis muscle was performed for morphometric analysis. Isokinetic evaluation of knee extensor torque, concentric and eccentric (90 and 180 degrees/sec), was performed simultaneously with vastus lateralis electromyographic activity evaluation. RESULTS: Significant differences were found in knee extensor torque (P < 0.05) and in normalized root mean square (P < 0.01) during the eccentric contractions (both velocities), with higher values for the control group. No differences were found during concentric contractions. The OA group presented greater values of the minimum diameter of type 1 fibers and greater proportion and relative cross-sectional area of type 2b fibers (P < 0.05). CONCLUSIONS: Men with early stages of knee OA do not present alterations of concentric strength but had decreased eccentric strength and morphologic quadriceps muscle changes, indicating neuromuscular adaptations. PMID- 25122095 TI - Review of secondary health conditions in postpolio syndrome: prevalence and effects of aging. AB - OBJECTIVE: This study sought to better understand the prevalence and the severity of secondary health conditions in individuals with postpolio syndrome (PPS) as well as the association between these conditions and aging. DESIGN: A scoping literature review was conducted searching electronic databases for studies published from 1986 to 2011. The scoping review provided information regarding the prevalence and associations of secondary health conditions in PPS with age or other duration-related variables. RESULTS: The findings indicate that (1) individuals with PPS experience a number of serious secondary health conditions; (2) the most common conditions or symptoms are fatigue, pain, respiratory and sleep complaints, and increased risk for falls; (3) reports of the associations between the frequency or the severity of conditions and age-related factors are variable, perhaps because of methodological inconsistencies between studies; and (4) there is a marked lack of longitudinal research examining the natural course of health conditions in people aging with PPS. CONCLUSIONS: Longitudinal research is needed to understand the course of health conditions and the impact of multiple secondary conditions in people aging with PPS. Efforts are also needed to develop and test the efficacy of interventions to prevent these secondary health conditions or reduce their negative impact. PMID- 25122096 TI - Effect of hip abduction exercise with manual pelvic fixation on recruitment of deep trunk muscles. AB - OBJECTIVE: The aim of this study was to determine whether side-lying hip abduction exercise while applying manual pelvic fixation is more effective than hip abduction without manual pelvic fixation for promoting deep trunk muscle activity. DESIGN: This is a cross-sectional study comparing deep trunk muscle activation between hip abduction exercise without and with manual pelvic fixation in ten participants. Muscle activation was measured using fine-wire and surface electromyography. RESULTS: Hip abduction with manual pelvic fixation was found to result in significantly more recruitment of all studied deep trunk muscles except the ipsilateral obliquus externus compared with hip abduction without manual pelvic fixation (P < 0.05). The greatest increased activation was seen in the ipsilateral deep and superficial multifidus. The increase in deep multifidus percentage of maximal voluntary contraction was greater than that of the rectus abdominis, the obliquus externus, the transversuus abdominis/obliquus internus, the lumbar erector spinae, the superficial multifidus, and the gluteus medius (P < 0.05). The superficial multifidus percentage of maximal voluntary contraction was significantly increased over that of the rectus abdominis and the obliquus externus (P < 0.05). Moderate correlation between deep and superficial multifidus activation was found (Pearson correlation coefficient, 0.537). CONCLUSIONS: Hip abduction training in the side-lying position while applying manual pelvic fixation seems to be more effective for recruiting deep trunk muscles for dynamic lumbar spinal stabilization. PMID- 25122097 TI - Strength training associated with task-oriented training to enhance upper-limb motor function in elderly patients with mild impairment after stroke: a randomized controlled trial. AB - OBJECTIVE: The aim of this study was to verify the effects of loaded exercises associated with a task-oriented training (TOT) program in the recovery of upper limb function in individuals with chronic hemiparesis after stroke. DESIGN: This study used a single-blinded, randomized controlled trial. Patients were included into two TOT groups: one that performed the task-oriented therapy without load (TOT group, n = 10) and another one that performed task-oriented therapy with personalized resistance (TOT_ST group, n = 10) for 6 wks, for a total of 12 sessions. Main measures included The Upper Extremity Performance Test, shoulder flexor and handgrip strength, shoulder active range of motion, motor impairment (Fugl-Meyer Scale), and muscle tone. RESULTS: The TOT_ST group demonstrated better scores relating to unilateral tasks and in the quality aspects of bilateral movements (The Upper Extremity Performance Test, P = 0.04) at the end of rehabilitation protocol. The highest muscle force gain was reached by the TOT_ST group for the shoulder flexors (P = 0.001). Similarly, the active range of motion (P = 0.01) and Fugl-Meyer scores (P = 0.001) were higher in the TOT_ST group compared with the TOT group. Both groups showed improvement after training. CONCLUSIONS: Strength training was able to intensify the upper-limb rehabilitation, as demonstrated by the superior scores achieved by the TOT_ST group in most of the evaluated parameters. Muscle strength training might be a pivotal element of the task-oriented rehabilitation program of chronic patients with mild impairment after stroke. PMID- 25122098 TI - Simultaneous bilateral biceps tendon rupture: a case report with practical sonographic diagnosis. AB - Simultaneous bilateral complete tear of the biceps tendons is a rare clinical entity with challenging treatment approaches. Current diagnostic imaging of rupture of the biceps tendon has reverted to magnetic resonance imaging; however, in the recent years, sonography has been widely used in musculoskeletal practice. The authors present a case of simultaneous bilateral biceps tendon rupture diagnosed on the basis of fundamental sonographic findings of the torn biceps tendons. PMID- 25122099 TI - Effects of low-level laser therapy on skeletal muscle repair: a systematic review. AB - A review of the literature was performed to demonstrate the most current applicability of low-level laser therapy (LLLT) for the treatment of skeletal muscle injuries, addressing different lasers, irradiation parameters, and treatment results in animal models. Searches were performed in the PubMed/MEDLINE, SCOPUS, and SPIE Digital Library databases for studies published from January 2006 to August 2013 on the use of LLLT for the repair of skeletal muscle in any animal model. All selected articles were critically appraised by two independent raters. Seventeen of the 36 original articles on LLLT and muscle injuries met the inclusion criteria and were critically evaluated. The main effects of LLLT were a reduction in the inflammatory process, the modulation of growth factors and myogenic regulatory factors, and increased angiogenesis. The studies analyzed demonstrate the positive effects of LLLT on the muscle repair process, which are dependent on irradiation and treatment parameters. The findings suggest that LLLT is an excellent therapeutic resource for the treatment of skeletal muscle injuries in the short-term. PMID- 25122100 TI - Lower gastrointestinal bleeding associated with diclofenac topical patch in a patient with colonic mass and on antiplatelet therapy for atrial fibrillation. AB - Topical formulations of diclofenac, a nonsteroidal anti-inflammatory drug commonly prescribed to treat musculoskeletal complaints such as osteoarthritis, low back pain, and myofascial pain, are available in the form of a solution, gel, and patch. The topical application of diclofenac results in substantially lower systemic exposure to diclofenac compared with oral diclofenac, resulting in a more favorable side effect profile. To the authors' knowledge, this is the first case report of a lower gastrointestinal bleed associated with diclofenac topical patch use in a 77 yr-old-woman with a history of colonic mass and atrial fibrillation on antiplatelet therapy. PMID- 25122101 TI - Rare communication between the musculocutaneous and median nerves in the forearm: its clinical significance. AB - Morphologic classifications of communication between musculocutaneous and median nerves are not based on the distribution and the function of the communicating branch. The authors report a rare case of such a communication with passage of the median nerve through the pronator teres muscle and discuss its clinical significance. The musculocutaneous nerve was divided into a lateral branch that continued to the lateral antebrachial cutaneous nerve and a medial branch that joined the median nerve in the forearm. The authors separated the nerve bundles and noted that the communicating branch derived from the sixth to seventh cervical nerves and supplied nerve fibers to the pronator teres muscle and the proper palmar digital nerve of the thumb. In addition, the median nerve penetrated the humeral head of the pronator teres muscle. Isolated musculocutaneous neuropathy with such a communication may cause unexpected symptoms such as sensory deficit in the palm and muscular weakness of the forearm and the thumb. PMID- 25122102 TI - Disease-in-a-dish: the contribution of patient-specific induced pluripotent stem cell technology to regenerative rehabilitation. AB - Advances in regenerative medicine technologies will lead to dramatic changes in how patients in rehabilitation medicine clinics are treated in the upcoming decades. The multidisciplinary field of regenerative medicine is developing new tools for disease modeling and drug discovery based on induced pluripotent stem cells. This approach capitalizes on the idea of personalized medicine by using the patient's own cells to discover new drugs, increasing the likelihood of a favorable outcome. The search for compounds that can correct disease defects in the culture dish is a conceptual departure from how drug screens were done in the past. This system proposes a closed loop from sample collection from the diseased patient, to in vitro disease model, to drug discovery and Food and Drug Administration approval, to delivering that drug back to the same patient. Here, recent progress in patient-specific induced pluripotent stem cell derivation, directed differentiation toward diseased cell types, and how those cells can be used for high-throughput drug screens are reviewed. Given that restoration of normal function is a driving force in rehabilitation medicine, the authors believe that this drug discovery platform focusing on phenotypic rescue will become a key contributor to therapeutic compounds in regenerative rehabilitation. PMID- 25122103 TI - Core stability, knee muscle strength, and anterior translation are correlated with postural stability in anterior cruciate ligament-reconstructed patients. AB - OBJECTIVE: The purpose of this study was to investigate the relationship of postural stability and lower extremity performance with core stability, knee laxity, and muscle strength in patients with anterior cruciate ligament reconstruction. DESIGN: Twenty-eight anterior cruciate ligament-reconstructed subjects were included in the study. Anterior knee laxity tests, isokinetic knee muscle strength tests, and core stability tests were performed. Single-limb postural stability was assessed in both eyes-open and eyes-closed positions on a static surface and an eyes-open condition on a foam surface. A single-legged hop test was performed to assess lower extremity performance. To detect differences between the operated and healthy leg, a Mann-Whitney U test was performed, and a correlation analysis was performed using the Spearman correlation coefficient. RESULTS: Knee muscle strength and laxity were different between the operated and healthy legs (P < 0.05). Postural stability scores correlated with core stability tests (P < 0.05) in both the operated and healthy legs. In the operated leg, knee laxity and muscle strength correlated with the mediolateral sway index on a foam surface (P < 0.05). Knee flexor and extensor muscle strength correlated with the single-legged hop for both legs (P < 0.05). CONCLUSIONS: Decreased core stability, decreased knee muscle strength, and increased knee laxity correlated with single-limb postural stability. Better hop performance was demonstrated with better knee flexor and extensor muscle strength and was independent from core stability. PMID- 25122104 TI - Iliac artery endofibrosis in a middle-aged female long-distance runner. AB - Exercise-induced iliac artery endofibrosis is a recently described abnormality of the external iliac artery that typically affects younger, healthy endurance athletes. Characteristic of the initially termed cyclist's iliac syndrome is lower limb pain during exercise with rapid recovery after exercise. This clinically complicated case describes an older female long-distance runner in whom an incorrect diagnosis of fibromuscular dysplasia was originally made when she presented with claudication and thrombosis of the right external iliac artery. A thrombectomy and bilateral balloon angioplasty were performed; however, her symptoms persisted. Four months later, she unexpectedly complained of dual calf claudication, a diagnosis of exercise-induced iliac artery endofibrosis was made, and a bilateral prosthetic graft bypass procedure was performed, which resulted in a good outcome. PMID- 25122105 TI - Letter to the editor regarding "Peripheral nerve stimulation compared with usual care for pain relief of hemiplegic shoulder pain" Am J Phys Med Rehabil 2014;93: 17-27. PMID- 25122106 TI - Stem cell therapy for intervertebral disk regeneration. AB - Intervertebral disk degeneration has been considered an irreversible process characterized by a decrease in cell viability, attenuation of proteoglycan and type II collagen synthesis, and dehydration of nucleus pulposus. Stem cell therapy specifically addresses the degenerative process and offers a potentially effective treatment modality. Current preclinical studies show that mesenchymal stem cells have the capacity to repair degenerative disks by differentiation toward chondrocyte-like cells, which produce proteoglycans and type II collagen. There has been evidence that mesenchymal stem cell transplantation into the intervertebral disk increases the intradiskal magnetic resonance imaging T2 signal intensity, increases the disk height, and decreases the degenerative grade in animal models. Appropriate selection of cell carriers/matrix is important because it may prevent cell leakage into the spinal canal and provide an environment that facilitates cell proliferation and differentiation. Although human cell therapy trials for degenerative disk disease are on the horizon, potential issues might arise. The authors hereby review the current state of regenerative cell therapy in degenerative disk disease, with emphasis in cell source, techniques for cellular expansion, induction, transplantation, potential benefit, and risks of the use of this novel medical armamentarium in the treatment of degenerative disk disease. PMID- 25122108 TI - Introduction to the series: Association of Academic Physiatrists research committee funding priority recommendations. PMID- 25122107 TI - An etiological paradigm shift for chronic hemiplegic shoulder pain. PMID- 25122109 TI - Elder abuse in Portugal: findings from the first national prevalence study. AB - In this study, we present findings of the Portuguese national prevalence study, "Aging and Violence," the purpose of which was to estimate the prevalence of abuse and neglect of older people in family settings over a 12-month period and examine the relationship between abuse and sociodemographic and health characteristics. Through a telephone survey of a representative probability sample (N = 1,123), we evaluated 12 abusive behaviors and demographic data. Overall, 12.3% of older adults experienced elder abuse in family settings. The prevalence rates of specific types were as follows: psychological, 6.3%; financial, 6.3%; physical, 2.3%; neglect, 0.4%; and sexual, 0.2%. Logistic regression was employed to determine the relationship between abuse and covariates. The study suggests that education level, age, and functional status are significantly associated with abuse. Accurate estimates of the prevalence of elder abuse and understanding of victim and perpetrator characteristics are fundamental to designing effective strategies for prevention and intervention. PMID- 25122110 TI - Mercury poisoning as a cause of intracranial hypertension. AB - Mercury poisoning is a rare but fatal toxicologic emergency. Neurologic manifestations involving the central nervous system are seen usually with chronic mercury intoxication. The most commonly seen complaints are headache, tremor, impaired cognitive skills, weakness, muscle atrophy, and paresthesia. Here, we present a male patient who was chronically exposed to elemental mercury and had papilledema and intracranial hypertension without parenchymal lesion in the central nervous system. A 12-year-old male patient was referred to our emergency room because of severe fatigue, generalized muscle pain and weakness, which was present for a month. Physical examination revealed painful extremities, decreased motor strength and the lack of deep tendon reflexes in lower extremities. He had mixed type polyneuropathy in his electromyography. Whole blood and 24-hour urinary mercury concentrations were high. A chelation therapy with succimer (dimercaptosuccinic acid) was started on the fourth day of his admission. On the seventh day of his admission, he developed headache and nausea, and bilateral papilledema and intracranial hypertension were detected on physical examination. Acetazolamide was started and after 1 month of treatment, the fundi examination was normal. The patient stayed in the hospital for 35 days and was then discharged with acetazolamide, vitamin B6, gabapentin, and followed as an outpatient. His clinical findings were relieving day by day. Although headache is the most common symptom in mercury poisoning, the clinician should evaluate the fundus in terms of intracranial hypertension. PMID- 25122111 TI - Rates and characteristics of radiographically detected intracerebral cavernous malformations after cranial radiation therapy in pediatric cancer patients. AB - Rates and characteristics of intracerebral cavernous malformations after cranial radiation therapy remain poorly understood. Herein we report on intracerebral cavernous malformations detected on follow-up imaging in pediatric cancer patients who received cranial radiation therapy at age <=18 years from 1980 to 2009. Through chart reviews (n = 362) and phone interviews (n = 104) of a retrospective cohort, we identified 10 patients with intracerebral cavernous malformations. The median latency time for detection of intracerebral cavernous malformations after cranial radiation therapy was 12 years (range 1-24 years) at a median age of 21.4 years (interquartile range = 15-28). The cumulative incidence was 3% (95% confidence interval 1%-8%) at 10 years post cranial radiation therapy and 14% (95% confidence interval 7%-26%) at 15 years. Three patients underwent surgical resection. Two surgical specimens were pathologically similar to sporadically occurring intracerebral cavernous malformations; one was consistent with capillary telangiectasia. Intracerebral cavernous malformations are common after cranial radiation therapy and can show a spectrum of histologic features. PMID- 25122112 TI - Succinic Semialdehyde Dehydrogenase Deficiency in a Chinese Boy: A Novel ALDH5A1 Mutation With Severe Phenotype. AB - Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessive disorder affecting catabolism of the neurotransmitter gamma-aminobutyric acid (GABA), with a wide range of clinical phenotype. We report a Malaysian Chinese boy with a severe early onset phenotype due to a previously unreported mutation. Urine organic acid chromatogram revealed elevated 4-hydroxybutyric acid. Magnetic resonance imaging (MRI) of the brain demonstrated cerebral atrophy with atypical putaminal involvement. Molecular genetic analysis showed a novel homozygous 3-bp deletion at the ALDH5A1 gene c.1501_1503del (p.Glu501del). Both parents were confirmed to be heterozygotes for the p.Glu501del mutation. The clinical course was complicated by the development of subdural hemorrhage probably as a result of rocking the child to sleep for erratic sleep-wake cycles. This case illustrates the need to recognize that trivial or unintentional shaking of such children, especially in the presence of cerebral atrophy, can lead to subdural hemorrhage. PMID- 25122114 TI - Structure of CfaA suggests a new family of chaperones essential for assembly of class 5 fimbriae. AB - Adhesive pili on the surface of pathogenic bacteria comprise polymerized pilin subunits and are essential for initiation of infections. Pili assembled by the chaperone-usher pathway (CUP) require periplasmic chaperones that assist subunit folding, maintain their stability, and escort them to the site of bioassembly. Until now, CUP chaperones have been classified into two families, FGS and FGL, based on the short and long length of the subunit-interacting loops between its F1 and G1 beta-strands, respectively. CfaA is the chaperone for assembly of colonization factor antigen I (CFA/I) pili of enterotoxigenic E. coli (ETEC), a cause of diarrhea in travelers and young children. Here, the crystal structure of CfaA along with sequence analyses reveals some unique structural and functional features, leading us to propose a separate family for CfaA and closely related chaperones. Phenotypic changes resulting from mutations in regions unique to this chaperone family provide insight into their function, consistent with involvement of these regions in interactions with cognate subunits and usher proteins during pilus assembly. PMID- 25122115 TI - Transcriptome of American oysters, Crassostrea virginica, in response to bacterial challenge: insights into potential mechanisms of disease resistance. AB - The American oyster Crassostrea virginica, an ecologically and economically important estuarine organism, can suffer high mortalities in areas in the Northeast United States due to Roseovarius Oyster Disease (ROD), caused by the gram-negative bacterial pathogen Roseovarius crassostreae. The goals of this research were to provide insights into: 1) the responses of American oysters to R. crassostreae, and 2) potential mechanisms of resistance or susceptibility to ROD. The responses of oysters to bacterial challenge were characterized by exposing oysters from ROD-resistant and susceptible families to R. crassostreae, followed by high-throughput sequencing of cDNA samples from various timepoints after disease challenge. Sequence data was assembled into a reference transcriptome and analyzed through differential gene expression and functional enrichment to uncover genes and processes potentially involved in responses to ROD in the American oyster. While susceptible oysters experienced constant levels of mortality when challenged with R. crassostreae, resistant oysters showed levels of mortality similar to non-challenged oysters. Oysters exposed to R. crassostreae showed differential expression of transcripts involved in immune recognition, signaling, protease inhibition, detoxification, and apoptosis. Transcripts involved in metabolism were enriched in susceptible oysters, suggesting that bacterial infection places a large metabolic demand on these oysters. Transcripts differentially expressed in resistant oysters in response to infection included the immune modulators IL-17 and arginase, as well as several genes involved in extracellular matrix remodeling. The identification of potential genes and processes responsible for defense against R. crassostreae in the American oyster provides insights into potential mechanisms of disease resistance. PMID- 25122118 TI - Clinical outcome and blood transfusion after infant cardiac surgery with a routine use of conventional ultrafiltration. AB - OBJECTIVE: Priming-related hemodilution is the culprit behind excessive body water accumulation, postoperative coagulopathy and enhanced blood transfusion in infant cardiac surgery patients. In this retrospective, observational study, clinical data were analyzed to assess the effect of conventional ultrafiltration on allogenic blood transfusion and patient clinical outcome. METHODS: All infants with a bodyweight up to 10 kg who underwent consequent cardiac surgery in 2011 and 2012 were eligible for the audit. Seventy patients, operated in accordance with existing pediatric protocol, enrolled in the control group. The study group consisted of 55 patients who were operated employing conventional ultrafiltration during bypass and recently adjusted hematocrit targets. The following variables were primarily investigated: hematocrit and colloid osmotic pressure value, total volume of blood products transfused and duration of postoperative mechanical ventilation. Secondary outcome measures were: postoperative urine production, postoperative blood loss, length of stay at the intensive care unit and hospital stay. RESULTS: There were no significant differences between the groups in relation to demographics or hematological and cardiopulmonary bypass data. The ultrafiltration volume removed from circulation during bypass in the study group was 171 +/- 99 ml. No significant difference between the groups was found with regard to the total allogenic blood transfusion (study group 216 +/- 92 ml versus control group 191 +/-93 ml; p = 0.136). All recorded clinical end points, duration of mechanical ventilation, duration of chest tube in situ, stay in ICU and stay in hospital, were similar between the groups. CONCLUSIONS: Routine use of conventional ultrafiltration during the cardiac surgery for patients with a bodyweight less than 10 kg was a safe technique that allowed us to achieve higher hematocrit levels at the end of the operation without additional transfusions of allogenic blood. On the other hand, ultrafiltration did not improve the clinical end points. PMID- 25122116 TI - Distinct patterns of the lipid alterations between genotype 1 and 2 chronic hepatitis C patients after viral clearance. AB - BACKGROUND: The hepatitis C virus (HCV) genotype-specific impacts on the host metabolic alterations remained inconclusive. METHODS: A prospective study including 229 (118 genotype 1 (G1) and 111 G2) consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR) >= 2.5). Paired t-tests were used to compare the pre- and post-treatment variables. RESULTS: Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR) but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001) and apolipoprotein A1 (p = 0.012) were only found in G2, whereas increased triglyceride/HDL (p = 0.01) ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019) and apolipoprotein A1 (p = 0.012) but a decrease in HOMA-IR (p = 0.04), C-peptide (p = 0.019) and hemoglobin A1c (p = 0.047) were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002) was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01) but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041) and triglyceride (p = 0.044) levels than G2 patients. CONCLUSIONS: G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR. PMID- 25122117 TI - The role of transapical cannulation in the operative management of acute aortic dissection. AB - OBJECTIVES: The aim of the study was to investigate the usefulness of transapical cannulation as the routine cannulation site in patients with acute aortic dissection and to compare it with other cannulation methods. METHODS: Between January 2010 and December 2013, emergency surgery was performed in 111 consecutive patients with acute type A aortic dissection. Patients were divided into two groups: transapical cannulation group and other cannulation sites group (including femoral and axillary artery cannulation). Pre-, intra- and postoperative data were compared between these two groups of patients. RESULTS: Transapical cannulation was the most frequent cannulation site (78 patients, 70.3%), the femoral artery was selected in 24 patients (21.6%) and the axillary artery in 9 patients (8.1%). The mortality rate in the transapical group was 16.7% and 18.2% when other cannulation sites were chosen (p=0.85). No difference in postoperative stroke rate (6.4% vs 9.1%, p=0.62, transapical vs other cannulation sites group, respectively), myocardial infarction (6.4% vs 6.1%, p=0.94) and postoperative acute renal insufficiency incidence (9% vs 6.1%, p=0.61) was found. CONCLUSIONS: Routine transapical cannulation in patients with acute type A aortic dissection is a fast and safe way to establish cardiopulmonary bypass. There is no difference in major operative outcomes after transapical cannulation when compared to the other cannulation sites. PMID- 25122119 TI - Modeling development in retinal afferents: retinotopy, segregation, and ephrinA/EphA mutants. AB - During neural development, neurons extend axons to target areas of the brain. Through processes of growth, branching and retraction these axons establish stereotypic patterns of connectivity. In the visual system, these patterns include retinotopic organization and the segregation of individual axons onto different subsets of target neurons based on the eye of origin (ocular dominance) or receptive field type (ON or OFF). Characteristic disruptions to these patterns occur when neural activity or guidance molecule expression is perturbed. In this paper we present a model that explains how these developmental patterns might emerge as a result of the coordinated growth and retraction of individual axons and synapses responding to position-specific markers, trophic factors and spontaneous neural activity. This model derives from one presented earlier (Godfrey et al., 2009) but which is here extended to account for a wider range of phenomena than previously described. These include ocular dominance and ON-OFF segregation and the results of altered ephrinA and EphA guidance molecule expression. The model takes into account molecular guidance factors, realistic patterns of spontaneous retinal wave activity, trophic molecules, homeostatic mechanisms, axon branching and retraction rules and intra-axonal signaling mechanisms that contribute to the survival of nearby synapses on an axon. We show that, collectively, these mechanisms can account for a wider range of phenomena than previous models of retino-tectal development. PMID- 25122120 TI - Genetic deletion of SEPT7 reveals a cell type-specific role of septins in microtubule destabilization for the completion of cytokinesis. AB - Cytokinesis terminates mitosis, resulting in separation of the two sister cells. Septins, a conserved family of GTP-binding cytoskeletal proteins, are an absolute requirement for cytokinesis in budding yeast. We demonstrate that septin dependence of mammalian cytokinesis differs greatly between cell types: genetic loss of the pivotal septin subunit SEPT7 in vivo reveals that septins are indispensable for cytokinesis in fibroblasts, but expendable in cells of the hematopoietic system. SEPT7-deficient mouse embryos fail to gastrulate, and septin-deficient fibroblasts exhibit pleiotropic defects in the major cytokinetic machinery, including hyperacetylation/stabilization of microtubules and stalled midbody abscission, leading to constitutive multinucleation. We identified the microtubule depolymerizing protein stathmin as a key molecule aiding in septin independent cytokinesis, demonstrated that stathmin supplementation is sufficient to override cytokinesis failure in SEPT7-null fibroblasts, and that knockdown of stathmin makes proliferation of a hematopoietic cell line sensitive to the septin inhibitor forchlorfenuron. Identification of septin-independent cytokinesis in the hematopoietic system could serve as a key to identify solid tumor-specific molecular targets for inhibition of cell proliferation. PMID- 25122122 TI - Unraveling the interplay of backbone rigidity and electron rich side-chains on electron transfer in peptides: the realization of tunable molecular wires. AB - Electrochemical studies are reported on a series of peptides constrained into either a 310-helix (1-6) or beta-strand (7-9) conformation, with variable numbers of electron rich alkene containing side chains. Peptides (1 and 2) and (7 and 8) are further constrained into these geometries with a suitable side chain tether introduced by ring closing metathesis (RCM). Peptides 1, 4 and 5, each containing a single alkene side chain reveal a direct link between backbone rigidity and electron transfer, in isolation from any effects due to the electronic properties of the electron rich side-chains. Further studies on the linear peptides 3-6 confirm the ability of the alkene to facilitate electron transfer through the peptide. A comparison of the electrochemical data for the unsaturated tethered peptides (1 and 7) and saturated tethered peptides (2 and 8) reveals an interplay between backbone rigidity and effects arising from the electron rich alkene side chains on electron transfer. Theoretical calculations on beta-strand models analogous to 7, 8 and 9 provide further insights into the relative roles of backbone rigidity and electron rich side-chains on intramolecular electron transfer. Furthermore, electron population analysis confirms the role of the alkene as a "stepping stone" for electron transfer. These findings provide a new approach for fine-tuning the electronic properties of peptides by controlling backbone rigidity, and through the inclusion of electron rich side-chains. This allows for manipulation of energy barriers and hence conductance in peptides, a crucial step in the design and fabrication of molecular-based electronic devices. PMID- 25122121 TI - Efficacy and safety of praziquantel, tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths. AB - BACKGROUND: Both tribendimidine and mebendazole are broad-spectrum drugs for anti intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths. METHOD: We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment. RESULTS: 156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel. CONCLUSION: Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura. TRIAL REGISTRATION: Controlled Trials.com ISRCTN55086560. PMID- 25122123 TI - The frequency and determinants of liver stiffness measurement failure: a retrospective study of "real-life" 38,464 examinations. AB - OBJECTIVE: To investigate the frequency and determinants of liver stiffness measurement (LSM) failure by means of FibroScan in "real-life" Chinese patients. METHODS: A total of 38,464 "real-life" Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC), alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC) and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m) and M probe (for adults) were used. LSM failure defined as zero valid shots (unsuccessful LSM), or the ratio of the interquartile range to the median of 10 measurements (IQR/M) greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM). RESULTS: LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464), among them, there were 958 cases (2.49%) with unsuccessful LSM, and 328 patients (0.85%) with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI) greater than 30 kg/m(2), female sex, age greater than 50 years, intercostal spaces (IS) less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P<0.0001). CONCLUSIONS: The principal reasons of LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC, decompensated LC, elder or female patients are higher. These results emphasize the need for adequate operator training, technological improvements and optimal criteria for specific patient subpopulations. PMID- 25122125 TI - Drug-pathway interaction prediction via multiple feature fusion. AB - Predicting new drug-pathway interactions from heterogeneous biological data is important not only for the understanding of various drug response and molecular interaction processes, but also for the development of novel drugs and the therapy of human diseases. In this paper, three different learning methods including the Bipartite Local Models method (BLM), Gaussian Interaction Profiles kernels (GIP) method and Graph-based Semi-supervised Learning method (GBSSL) were used to predict drug-pathway interactions. To realize the purpose, drugs were firstly represented by functional groups and chemical structure similarity, and pathways were represented by their related gene expressions and semantic similarity based features. Then, the parameter optimization procedures were further adopted to deal with heterogeneous data sources. As a result, the proposed methods achieved a high ROC curve score (AUC score) over 0.95, which validated the effectiveness of multiple information integration. Moreover, several new potential drug-pathway interactions were identified for further biological function research. PMID- 25122124 TI - Snail promotes epithelial mesenchymal transition in breast cancer cells in part via activation of nuclear ERK2. AB - Snail transcription factor is up-regulated in several cancers and associated with increased tumor migration and invasion via induction of epithelial-to-mesenchymal transition (EMT). MAPK (ERK1/2) signaling regulates cellular processes including cell motility, adhesion, and invasion. We investigated the regulation of ERK1/2 by Snail in breast cancer cells. ERK1/2 activity (p-ERK) was higher in breast cancer patient tissue as compared to normal tissue. Snail and p-ERK were increased in several breast cancer cell lines as compared to normal mammary epithelial cells. Snail knockdown in MDA-MB-231 and T47-D breast cancer cells decreased or re-localized p-ERK from the nuclear compartment to the cytoplasm. Snail overexpression in MCF-7 breast cancer cells induced EMT, increased cell migration, decreased cell adhesion and also increased tumorigenicity. Snail induced nuclear translocation of p-ERK, and the activation of its subcellular downstream effector, Elk-1. Inhibiting MAPK activity with UO126 or knockdown of ERK2 isoform with siRNA in MCF-7 Snail cells reverted EMT induced by Snail as shown by decreased Snail and vimentin expression, decreased cell migration and increased cell adhesion. Overall, our data suggest that ERK2 isoform activation by Snail in aggressive breast cancer cells leads to EMT associated with increased cell migration and decreased cell adhesion. This regulation is enhanced by positive feedback regulation of Snail by ERK2. Therefore, therapeutic targeting of ERK2 isoform may be beneficial for breast cancer. PMID- 25122126 TI - Disrupted TH17/Treg balance in patients with chronic low back pain. AB - Chronic low back pain (CLBP) is a leading cause of disability and costs in health care systems worldwide. Despite extensive research, the exact pathogenesis of CLBP, particularly the individual risk of chronification remains unclear. To investigate a possible role of the adaptive immune system in the pathophysiology of CLBP, we analyzed T cell related cytokine profiles, T cell related mRNA expression patterns and the distribution of T cell subsets in 37 patients suffering from nonspecific CLBP before and after multimodal therapy in comparison to 25 healthy controls. Serum patterns of marker cytokines were analyzed by Luminex technology, mRNA expression of cytokines and specific transcription factors was measured by real-time PCR, and distribution of TH1-, TH2-, TH17- and regulatory T cell (Tregs) subsets was determined by multicolor flow cytometry. We found that CLBP patients exhibit an increased number of anti-inflammatory Tregs, while pro-inflammatory TH17 cells are decreased, resulting in an altered TH17/Treg ratio. Accordingly, FoxP3 and TGF-beta-mRNA expression was elevated, while expression of IL-23 was reduced. Serum cytokine analyses proved to be unsuitable to monitor the adaptive immune response in CLBP patients. We further show that even after successful therapy with lasting reduction of pain, T cell subset patterns remained altered after a follow-up period of 6 months. These findings suggest an involvement of TH17/Treg cells in the pathogenesis of CLBP and emphasize the importance of these cells in the crosstalk of pain and immune response. TRIAL REGISTRATION: German Clinical Trial Register: Registration Trial DRKS00005954. PMID- 25122128 TI - Examination of the Relationship Between Hopelessness Levels and Coping Strategies Among the Family Caregivers of Patients With Cancer. AB - BACKGROUND: Family caregivers who provide care for cancer patients may have to cope with a variety of physical, social, and economic problems during the caregiving process. A sense of hopelessness seems to lead to increasingly negative evaluations of new situations and less effective coping strategies. OBJECTIVE: The objective of the study was to examine the relationship between hopelessness and the coping strategies of the family caregivers of oncology patients. METHODS: This cross-sectional, descriptive correlational design study was carried out in the adult oncology unit and outpatient radiation oncology units of a university hospital in Turkey. The research sample was composed of 110 family caregivers. A sociodemographic data form, the Coping Stress Strategies Scale, and the Beck Hopelessness Scale were used in face-to-face interviews. RESULTS: Significant correlations were found between hopelessness and coping strategies. There was a positive correlation between hopelessness and the helpless approaches, which constitute a part of the emotion-focused coping strategies (r = 0.254, P < .01). There was a negative correlation between hopelessness and problem-focused coping strategies (optimistic approach and seeking social support) (r = -0.484, P < .01; r = -0.190, P < .05). CONCLUSION: In our study, we found that when the hopes of family caregivers are raised, they may adopt a more optimistic approach, and seek more social support, and display more effective coping strategies. IMPLICATIONS FOR PRACTICE: This study could be used to help develop nursing interventions and efficient coping strategies. It suggests how oncology nurses may support family caregivers to increase their level of hope. PMID- 25122127 TI - Genomic distribution of H3K9me2 and DNA methylation in a maize genome. AB - DNA methylation and dimethylation of lysine 9 of histone H3 (H3K9me2) are two chromatin modifications that can be associated with gene expression or recombination rate. The maize genome provides a complex landscape of interspersed genes and transposons. The genome-wide distribution of DNA methylation and H3K9me2 were investigated in seedling tissue for the maize inbred B73 and compared to patterns of these modifications observed in Arabidopsis thaliana. Most maize transposons are highly enriched for DNA methylation in CG and CHG contexts and for H3K9me2. In contrast to findings in Arabidopsis, maize CHH levels in transposons are generally low but some sub-families of transposons are enriched for CHH methylation and these families exhibit low levels of H3K9me2. The profile of modifications over genes reveals that DNA methylation and H3K9me2 is quite low near the beginning and end of genes. Although elevated CG and CHG methylation are found within gene bodies, CHH and H3K9me2 remain low. Maize has much higher levels of CHG methylation within gene bodies than observed in Arabidopsis and this is partially attributable to the presence of transposons within introns for some maize genes. These transposons are associated with high levels of CHG methylation and H3K9me2 but do not appear to prevent transcriptional elongation. Although the general trend is for a strong depletion of H3K9me2 and CHG near the transcription start site there are some putative genes that have high levels of these chromatin modifications. This study provides a clear view of the relationship between DNA methylation and H3K9me2 in the maize genome and how the distribution of these modifications is shaped by the interplay of genes and transposons. PMID- 25122129 TI - Community Nursing Care of Chinese-Australian Cancer Patients: A Qualitative Study. AB - BACKGROUND: Providing quality care and support to cancer patients from minority cultures can challenge community nurses when language barriers and cultural complexities intersect with the need for complex care. OBJECTIVES: This article reports on a qualitative study that explores interactions between community nurses and Chinese-Australian cancer patients. METHODS: The research method focused on particular nurse-patient encounters and involved preencounter and postencounter interviews with the nurse, postencounter interviews with the patient, and observation of the encounters. Participants included community nurses, Chinese cancer patients being cared for at home, and their carers if present. RESULTS: Four themes were conceptualized: (1) the impact of language barriers on nurse-patient interactions, (2) patient understandings of the scope and objectives of healthcare services, (3) cultural complexities and sensitivities, and (4) valued care and support. The study demonstrates that, although many nurses do provide comprehensive, culturally competent care, language barriers can lead to task-oriented rather than comprehensive approaches, and other cultural complexities do have an impact on patient experiences and on the quality of nurse-patient interactions. Nevertheless, most patient participants experienced a feeling of security as a result of regular contact with a community nursing service. CONCLUSION: Cancer patients with complex care needs but limited English proficiency require support to negotiate complicated community services networks. Culturally competent community nurses can provide this support. IMPLICATIONS FOR PRACTICE: The study highlights the need for continuing cultural competence education for community nurses and the importance of careful discharge planning to ensure continuity of care for this vulnerable patient group. PMID- 25122131 TI - Social Cultural Influences on Breast Cancer Views and Breast Health Practices Among Chinese Women in the United Kingdom. AB - BACKGROUND: Incidence rates for breast cancer have increased significantly among Chinese women, accompanied by low utilization of breast screening and delay in symptom presentation. OBJECTIVE: The aims of this study were to explore (1) views on breast cancer and breast health among Chinese women in the United Kingdom and (2) the potential influence of social and cultural context on views and screening behavior. METHODS: Qualitative interviews were carried out with 22 Chinese women. Pertinent aspects of Grounded Theory methods, including simultaneous data collection and analysis, constant comparison, and memo writing, were used. RESULTS: Four themes emerged: cultural views on breast cancer, information sources and knowledge, breast screening practice, and views on healthcare services. The theme views on breast cancer had 3 subthemes: a fearful disease, taboo, and fatalism. Aspects of traditional Chinese culture had important influences on Chinese women's views on breast cancer. Self-care formed the most significant strategy to promote health and prevent illness. Although the study found high utilization of breast screening when offered, only 6 women reported breast awareness practices. CONCLUSIONS: This study found that traditional beliefs were not the sole determinant of breast health behavior. The way in which breast screening services are offered in the United Kingdom may reduce the significance of cultural views and shape individuals' health behavior. IMPLICATIONS FOR PRACTICE: Findings indicate that information on breast awareness should be delivered to this group of women in Chinese by health professionals through Chinese mass media. PMID- 25122130 TI - Effects of a Randomized Controlled Trial to Increase Repeat Mammography Screening in Iranian Women. AB - BACKGROUND: Although mammography use has increased in developed countries, regular screening in developing countries including Iran remains low. Multiple frameworks, including the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB), have been used to understand screening practices among Iranians. The HBM includes intrapersonal constructs such as perceptions of breast cancer and mammography. The TPB includes interpersonal and environmental constructs, such as perceived control and subjective norms. OBJECTIVES: The current study had 2 objectives: (1) to examine changes in the HBM and TPB constructs and repeat mammography screening in women receiving either intervention and women in the control group and (2) to compare changes in the HBM and TPB constructs and repeat mammography screening across the 2 interventions. METHODS: One hundred eight-four women from 3 randomly selected health centers in Sanandaj, Iran, participated. Eligibility criteria were being 50 years or older, having received a mammogram in the past 2 to 3 years, and no intention to obtain a mammogram within the next year. RESULTS: The TPB and HBM participants exhibited greater changes in the HBM and TPB constructs and were more likely to have a mammogram relative to control participants. The TPB and HBM participants exhibited comparable changes in constructs and repeat mammography. CONCLUSION: Findings suggest both interventions equally improved mammography screening. Additional studies are furthermore warranted to address nonadherent Iranian women's needs in line with these conceptual models. IMPLICATIONS FOR PRACTICE: Use of the HBM and TPB constructs in clinical practice may be helpful to promote continued screening among this population. PMID- 25122133 TI - Ways of coping with stress and perceived social support in gynecologic cancer patients. AB - BACKGROUND: Stress is commonly encountered among cancer patients and may be a challenge affecting immune system resistance. Social support may contribute positively to the health of cancer patients, playing a role in coping with stress. OBJECTIVE: The aim of this study was to determine whether ways of coping are related to social support given to women with gynecologic cancer. METHODS: The study was performed as a cross-sectional design in a university hospital in Istanbul, Turkey, with 221 women with gynecologic cancer; the data were collected via 3 questionnaires, the first with sociodemographic and clinical features, the second with multidimensional scale of perceived social support, and the third with the scale of ways of coping with stress. RESULTS: Women with gynecologic cancer who were employed and declared their incomes as balanced and reported more years of education were more likely to perceive higher social support and to use the ineffective coping ways with stress at a lower rate (P < .05) than other participants. Based on correlational analysis, effective coping ways with stress increase as perceived social support from family, friends, significant other, and total increases (P < .05). CONCLUSIONS: Social support from family members is the mainstay of coping with stress by women with gynecologic cancer. IMPLICATIONS FOR PRACTICE: Nurses are indispensable in increasing social support required by women with gynecologic cancer. Well-trained clinical nurses via in-service programs should be experienced and aware of women diagnosed with gynecologic cancer in need of social support during hospital visits and provide necessary guidance. PMID- 25122132 TI - Gender and Role Differences in Couples' Communication During Cancer Survivorship. AB - BACKGROUND: Individuals with cancer and their partners often experience communication difficulties. However, questions still remain regarding the influence of gender and role in cancer survivor-partner communication within couples. OBJECTIVE: The current study intended to examine the communication patterns in breast, colorectal, and prostate cancer survivor-partner couples during cancer survivorship and whether gender and role differences in couples communication exist. METHODS: The dominant-less dominant method of sequential mixed design was used. Ten couples who were recruited from the University Hospital registry in Cleveland, Ohio, participated in both mail surveys and individual interviews. Family and cancer-related communication was assessed in the quantitative phase. RESULTS: Both male survivors and partners demonstrated better family communication scores compared with their female counterparts, whereas there were no gender differences in the cancer-related communication scores. In the qualitative phase, 3 major themes were identified: (1) selective sharing of cancer-related issues, (2) initiation of cancer-related communication, and (3) emotional reaction in communication. The patterns associated with these themes differed between the male survivor-female partner and female survivor-male partner couples. CONCLUSIONS: This study provides new knowledge about family and cancer-related communication. Our findings highlight the importance of understanding different perspectives in the quality of communication by gender and role. IMPLICATIONS FOR PRACTICE: Exploring couples' communication patterns by gender and role stimulates the research and the development of effective consumer centered communication interventions. The findings provide assessment tools to inform dyadic communication patterns for clinical and scientific purposes. PMID- 25122134 TI - Patients With Hepatocellular Carcinoma Near the End of Life: A Longitudinal Qualitative Study of Their Illness Experiences. AB - BACKGROUND: In the United States, the incidence of hepatocellular carcinoma (HCC) is rising. For those diagnosed with terminal HCC, there is no curative treatment and duration of survival is typically 1 to 2 years. Research on illness and treatment experiences toward the end of life for patients with terminal HCC is limited. OBJECTIVE: The aim of this study was to explore the illness experiences of patients with terminal HCC as they approached the end of life. METHODS: This study used a prospective, longitudinal descriptive design. Interview data were collected from 14 patients once a month for up to 6 months, for a total of 45 interviews. Data were analyzed using conventional content analysis. RESULTS: Three major themes (illness perceptions, decision to start treatment, and navigating treatment over time) and 10 subthemes were identified that were reflected across time in all patient experiences. Patients faced challenges with symptom experiences, treatment decisions, and unmet information needs affecting their quality of life. CONCLUSIONS: Gaining knowledge about the challenges facing patients with HCC is crucial for designing interventions that optimize their quality of life. IMPLICATIONS FOR PRACTICE: Healthcare professionals may improve the quality of life of patients with terminal HCC by eliciting patients' perceptions of their illness and treatment decisions, symptom experiences, and information needs as the disease progresses and providing symptom management and offering information tailored to their needs. Care for patients with HCC who are approaching the end of life should be multidisciplinary and include timely referral to palliative care. PMID- 25122138 TI - Model study of the pressure build-up during subcutaneous injection. AB - In this study we estimate the subcutaneous tissue counter pressure during drug infusion from a series of injections of insulin in type 2 diabetic patients using a non-invasive method. We construct a model for the pressure evolution in subcutaneous tissue based on mass continuity and the flow laws of a porous medium. For equivalent injection forces we measure the change in the infusion rate between injections in air at atmospheric pressure and in tissue. From a best fit with our model, we then determine the flow permeability as well as the bulk modulus of the tissue, estimated to be of the order 10-11-10-10 m2 and 105 Pa, respectively. The permeability is in good agreement with reported values for adipose porcine tissue. We suggest our model as a general way to estimate the pressure build-up in tissue during subcutaneous injection. PMID- 25122137 TI - Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice. AB - MED1 (Mediator complex subunit 1) is a co-activator of various transcription factors that function in multiple transcriptional pathways. We have already established keratinocyte-specific MED1 null mice (Med1(epi-/-)) that develop epidermal hyperplasia. Herein, to investigate the function(s) of MED1 in skin wound healing, full-thickness skin wounds were generated in Med1(epi-/-) and age matched wild-type mice and the healing process was analyzed. Macroscopic wound closure and the re-epithelialization rate were accelerated in 8-week-old Med1(epi /-) mice compared with age-matched wild-type mice. Increased lengths of migrating epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis were observed in 8-week-old Med1(epi-/-) mice, whereas wound contraction and the area of alpha-SMA-positive myofibroblasts in the granulation tissue were unaffected. Migration was enhanced in Med1(epi-/-) keratinocytes compared with wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of follistatin was significantly decreased in Med1(epi-/-) keratinocytes. Moreover, the mitogen-activated protein kinase pathway was enhanced before and after treatment of Med1(epi-/-) keratinocytes with activin A in vitro. Cell-cycle analysis showed an increased ratio of S phase cells after activin A treatment of Med1(epi-/-) keratinocytes compared with wild-type keratinocytes. These findings indicate that the activin-follistatin system is involved in this acceleration of skin wound healing in 8-week-old Med1(epi-/-) mice. On the other hand, skin wound healing in 6-month-old Med1(epi-/-) mice was significantly delayed with decreased numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive label retaining cells in hair follicles compared with age-matched wild-type mice. These results agree with our previous observation that hair follicle bulge stem cells are reduced in older Med1(epi-/-) mice, indicating a decreased contribution of hair follicle stem cells to epidermal regeneration after wounding in 6-month old Med1(epi-/-) mice. This study sheds light on the novel function of MED1 in keratinocytes and suggests a possible new therapeutic approach for skin wound healing and aging. PMID- 25122139 TI - Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques. AB - OBJECTIVE: Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques. METHODS: Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort). RESULTS: We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585-11267) area under the curve (AUC) vs. 9633 (3580-21565) AUC, P<0.001). Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean +/- SD; 8969 +/- 3485 AUC vs. 7020 +/- 3442 AUC, P = 0.02). All associations remained significant after adjustment for age, sex and use of drugs against platelet activation. CONCLUSION: Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques. PMID- 25122140 TI - Construction and validation of a regulatory network for pluripotency and self renewal of mouse embryonic stem cells. AB - A 30-node signed and directed network responsible for self-renewal and pluripotency of mouse embryonic stem cells (mESCs) was extracted from several ChIP-Seq and knockdown followed by expression prior studies. The underlying regulatory logic among network components was then learned using the initial network topology and single cell gene expression measurements from mESCs cultured in serum/LIF or serum-free 2i/LIF conditions. Comparing the learned network regulatory logic derived from cells cultured in serum/LIF vs. 2i/LIF revealed differential roles for Nanog, Oct4/Pou5f1, Sox2, Esrrb and Tcf3. Overall, gene expression in the serum/LIF condition was more variable than in the 2i/LIF but mostly consistent across the two conditions. Expression levels for most genes in single cells were bimodal across the entire population and this motivated a Boolean modeling approach. In silico predictions derived from removal of nodes from the Boolean dynamical model were validated with experimental single and combinatorial RNA interference (RNAi) knockdowns of selected network components. Quantitative post-RNAi expression level measurements of remaining network components showed good agreement with the in silico predictions. Computational removal of nodes from the Boolean network model was also used to predict lineage specification outcomes. In summary, data integration, modeling, and targeted experiments were used to improve our understanding of the regulatory topology that controls mESC fate decisions as well as to develop robust directed lineage specification protocols. PMID- 25122142 TI - Making biomolecular simulations accessible in the post-Nobel Prize era. PMID- 25122135 TI - Small molecule adenosine 5'-monophosphate activated protein kinase (AMPK) modulators and human diseases. AB - Adenosine 5'-monophosphate activated protein kinase (AMPK) is a master sensor of cellular energy status that plays a key role in the regulation of whole-body energy homeostasis. AMPK is a serine/threonine kinase that is activated by upstream kinases LKB1, CaMKKbeta, and Tak1, among others. AMPK exists as alphabetagamma trimeric complexes that are allosterically regulated by AMP, ADP, and ATP. Dysregulation of AMPK has been implicated in a number of metabolic diseases including type 2 diabetes mellitus and obesity. Recent studies have associated roles of AMPK with the development of cancer and neurological disorders, making it a potential therapeutic target to treat human diseases. This review focuses on the structure and function of AMPK, its role in human diseases, and its direct substrates and provides a brief synopsis of key AMPK modulators and their relevance in human diseases. PMID- 25122141 TI - Inhibition of the TRAIL death receptor by CMV reveals its importance in NK cell mediated antiviral defense. AB - TNF-related apoptosis inducing ligand (TRAIL) death receptors (DR) regulate apoptosis and inflammation, but their role in antiviral defense is poorly understood. Cytomegaloviruses (CMV) encode many immune-modulatory genes that shape host immunity, and they utilize multiple strategies to target the TNF family cytokines. Here we show that the m166 open reading frame (orf) of mouse CMV (MCMV) is strictly required to inhibit expression of TRAIL-DR in infected cells. An MCMV mutant lacking m166 expression (m166stop) is severely compromised for replication in vivo, most notably in the liver, and depleting natural killer (NK) cells, or infecting TRAIL-DR-/- mice, restored MCMV-m166stop replication completely. These results highlight the critical importance for CMV to have evolved a strategy to inhibit TRAIL-DR signaling to thwart NK-mediated defenses. PMID- 25122143 TI - Comprehensive CFTR gene analysis of the French cystic fibrosis screened newborn cohort: implications for diagnosis, genetic counseling, and mutation-specific therapy. AB - PURPOSE: Newborn screening (NBS) for cystic fibrosis (CF) was implemented throughout France in 2002. It involves a four-tiered procedure: immunoreactive trypsin (IRT)/DNA/IRT/sweat test [corrected] was implemented throughout France in 2002. The aim of this study was to assess the performance of molecular CFTR gene analysis from the French NBS cohort, to evaluate CF incidence, mutation detection rate, and allelic heterogeneity. METHODS: During the 8-year period, 5,947,148 newborns were screened for cystic fibrosis. The data were collected by the Association Francaise pour le Depistage et la Prevention des Handicaps de l'Enfant. The mutations identified were classified into four groups based on their potential for causing disease, and a diagnostic algorithm was proposed. RESULTS: Combining the genetic and sweat test results, 1,160 neonates were diagnosed as having cystic fibrosis. The corresponding incidence, including both the meconium ileus (MI) and false-negative cases, was calculated at 1 in 4,726 live births. The CF30 kit, completed with a comprehensive CFTR gene analysis, provides an excellent detection rate of 99.77% for the mutated alleles, enabling the identification of a complete genotype in 99.55% of affected neonates. With more than 200 different mutations characterized, we confirmed the French allelic heterogeneity. CONCLUSION: The very good sensitivity, specificity, and positive predictive value obtained suggest that the four-tiered IRT/DNA/IRT/sweat test procedure may provide an effective strategy for newborn screening for cystic fibrosis. PMID- 25122146 TI - Feasibility study to quantify the auditory and social environment of older adults using a digital language processor. AB - OBJECTIVE: To investigate the feasibility of using a digital language processor (DLP) to objectively quantify the auditory and social environment of older adults. DESIGN: Thirty-seven participants aged 64 to 91 years residing in a retirement community were asked to wear a DLP to record their auditory and language environment during 1 waking day. Recordings were analyzed with specialized software to derive quantitative estimates such as the number of spoken words heard and percentage of time spent around meaningful speech versus television/radio. RESULTS: Adequate DLP recordings that began before 10 AM and lasted for 10 hours or greater were collected from 24 participants. The mean duration of recording was 13 hours and 13 minutes, and individuals spent a mean of 26.7% (range, 4%-58%) of their waking day near a television or other electronic sounds. The projected mean word count over a maximum of 16 hours was 33,141 with nearly a 14-fold range between the lowest and highest observed values (range, 5120-77,882). CONCLUSIONS: High-quality objective data on the auditory environment of older adults can be feasibly measured with the DLP. Findings from this study may guide future studies investigating auditory and language outcomes in older adults. PMID- 25122147 TI - Influence of laser-assisted cochleostomy on acoustically evoked compound action potentials in the guinea pig. AB - HYPOTHESIS: Making a cochleostomy with a laser can affect the inner ear function. BACKGROUND: Different types of lasers can be used to create a fenestration in the footplate of the stapes during stapedotomy. Because of variations in absorption spectra of the laser light in various tissues or fluids, each laser has its own characteristics and possible side effects. MATERIALS AND METHODS: The basal turns of the cochleae of 20 guinea pigs were fenestrated using 4 types of lasers (thulium, KTP, CO2, diode; all groups n = 4). A control group (n = 4) was included to correct for the effects of the surgery alone. At 3 different time points, acoustically evoked compound action potentials (CAPs) were recorded at 5 frequencies and at different sound pressure levels. N1-P2 amplitudes were measured, and subsequently, thresholds were calculated. A repeated measures analysis of variance was used to investigate differences between groups. RESULTS: There was a decrease in CAP amplitudes and an increase in CAP thresholds after cochleostomy with each laser. The increase in thresholds was significantly larger for higher frequencies. The thulium laser evoked the largest threshold shifts, the KTP laser the smallest with the CO2, and diode lasers in intermediate positions. Overall, there was an increase in latencies after treatment. CONCLUSION: Laser treatment on or near the cochlea can cause damage to the sensitivity of the cochlea for sound. The thulium laser seems to be the worst choice in this respect. PMID- 25122145 TI - Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion. AB - PURPOSE: The aim of this study was to identify the genetic cause of early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy in a consanguineous family. METHODS: An affected 6-month-old child underwent neurological and ophthalmological examinations. Genetic analyses included homozygosity mapping, copy number analysis, conventional polymerase chain reaction, Sanger sequencing, quantitative polymerase chain reaction, and whole exome sequencing. Expression analysis of GRID2 was performed by quantitative polymerase chain reaction and immunohistochemistry. RESULTS: A homozygous deletion of exon 2 of GRID2 (p.Gly30_Glu81del) was identified in the proband. GRID2 encodes an ionotropic glutamate receptor known to be selectively expressed in cerebellar Purkinje cells. Here, we demonstrated GRID2 expression in human adult retina and retinal pigment epithelium. In addition, Grid2 expression was demonstrated in different stages of murine retinal development. GRID2 immunostaining was shown in murine and human retina. Whole-exome sequencing in the proband did not provide arguments for other disease-causing mutations, supporting the idea that the phenotype observed represents a single clinical entity. CONCLUSION: We identified GRID2 as an underlying disease gene of early onset autosomal recessive cerebellar ataxia with retinal dystrophy, expanding the clinical spectrum of GRID2 deletion mutants. We demonstrated for the first time GRID2 expression and localization in human and murine retina, providing evidence for a novel functional role of GRID2 in the retina. PMID- 25122144 TI - Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations. AB - PURPOSE: The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established. METHODS: We analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations. RESULTS: We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding. CONCLUSION: These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196. PMID- 25122148 TI - Management of incus necrosis in revision stapedectomy using hydroxyapatite bone cement. AB - OBJECTIVE: Review audiological outcomes after revision stapedectomy using hydroxyapatite cement. STUDY DESIGN: Retrospective case review. SETTING: Tertiary neurotological referral center. PATIENTS: Thirty-seven cases of previously treated otosclerosis where incus erosion was observed during revision stapedectomy. INTERVENTION(S): Hydroxyapatite cement was used to rebuild the eroded incus and stabilize the prosthesis during revision stapedectomy. MAIN OUTCOME MEASURE(S): Pre- and postoperative bone conduction (BC) and air conduction (AC) pure-tone averages (PTA) (0.5, 1, 2, 3 kHz) including high tone BC (1, 2, 4 kHz), air-bone gap (ABG), and speech discrimination scores were measured. Short-term (3 wk) and longer-term (average 12 mo) hearing outcomes were measured. Data are reported according to the most recent guidelines of the AAO HNS Committee on Hearing and Equilibrium. RESULTS: Among 37 ears undergoing revision stapedectomy with hydroxyapatite cement, the AC PTA was 59.8 dB preoperatively and 34.6 dB postoperatively (p < 0.0001) at latest follow-up. The mean postoperative ABG was 8.8 dB (SD = 8.6, range -1.3-36.3 dB) while a mean improvement of 2.1 dB (SD = 6.5, range -8.33-15.0 dB) of the high tone BC PTA was observed. One revision case was noted during the follow-up period. CONCLUSION: Hydroxyapatite cement is useful to reconstruct and stabilize the prosthesis in revision stapedectomy when erosion of the long process is encountered. Short- and longer-term hearing results are favorable when compared to previously reported results of revision stapedectomy. PMID- 25122149 TI - Bilateral hearing loss heralding sporadic Creutzfeldt-Jakob disease: a case report and literature review. AB - OBJECTIVE: To report a case of sporadic Creutzfeldt-Jakob disease (CJD) with bilateral hearing loss at onset and literature review of the scarce cases of CJD with similar audiologic manifestations at presentation. CASE REPORT: A 67-yr-old man presented to the hospital for evaluation of rapid progression of behavioral decline, unsteady gait, and bilateral hearing loss. Three months before admission, he abruptly developed bilateral hypoacusis without associated tinnitus or vertigo. Shortly after, his family noted an ataxic gait and behavioral changes, for example, paranoid delusions. Initial workup, including a complete autoimmune panel and heavy metals, infectious, toxicology, and paraneoplastic panel (e.g., anti-Hu, anti-VGKC), was conducted. Electroencephalography revealed diffuse generalized slowing without periodic complexes. The presence of distortion product otoacoustic emissions bilaterally was consistent with normal cochlear function, suggesting a retrocochlear origin for symptoms of hearing loss. In the meantime, the patient developed startle myoclonus. The brain magnetic resonance imaging demonstrated asymmetric cortical ribbon along with T2 FLAIR signal hyperintensities of bilateral basal ganglia. Later on, the protein 14-3-3 in the cerebrospinal fluid came back positive, which supported the diagnosis of CJD. Only three cases of CJD with deafness at onset have been published: one sporadic, associated with symptoms suggestive of polyneuropathy; and the other two familial, with the E200K mutation. One presented with symptoms of polyneuropathy and the other with typical features. CONCLUSION: This case illustrates the phenotypic variability of presentation of CJD in a patient with hearing loss as the initial manifestation. In patients with subacute bilateral hypoacusis and signs of dementia, the differential diagnosis of CJD must be taken into consideration. PMID- 25122150 TI - Sex differences in response to tadalafil in pulmonary arterial hypertension. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease with high rates of morbidity and mortality. Current therapies improve symptoms, functional capacity, and, in select cases, survival. Little is known about patient factors that may predict the likelihood of patient-important, clinically relevant responses to therapy such as the 6-min walk distance (6MWD) and health related quality of life (HRQoL). METHODS: Data from the randomized clinical trial of tadalafil in PAH were used. Adjusted logistic regression models were created to examine the relationship between baseline characteristics and odds of achieving the minimal important difference (MID) in three parameters, defined as either a > 33-m increase in 6MWD, a > 5-unit increase in physical component summary score of the Medical Outcomes Study Short Form-36 (SF-36), or a > 5-unit increase in mental component summary score of the SF-36. RESULTS: The study included 405 subjects. Younger age, male sex, lower baseline 6MWD, and disease etiology were associated with greater odds of achieving the MID for the 6-min walk test. Active treatment, younger age, and male sex were associated with greater odds of achieving the MID for the physical component summary score. Male sex was associated with greater odds of achieving the MID for the mental component summary score. CONCLUSIONS: Age, sex, baseline functional capacity, and disease etiology are variably associated with the likelihood of achieving clinically relevant responses in patient-important outcomes to PAH-specific therapy such as 6MWD and HRQoL. The increased likelihood of response in men compared with women is a novel finding and may reflect pathophysiologic differences between sexes. PMID- 25122152 TI - The Arabidopsis 14-3-3 protein RARE COLD INDUCIBLE 1A links low-temperature response and ethylene biosynthesis to regulate freezing tolerance and cold acclimation. AB - In plants, the expression of 14-3-3 genes reacts to various adverse environmental conditions, including cold, high salt, and drought. Although these results suggest that 14-3-3 proteins have the potential to regulate plant responses to abiotic stresses, their role in such responses remains poorly understood. Previously, we showed that the RARE COLD INDUCIBLE 1A (RCI1A) gene encodes the 14 3-3 psi isoform. Here, we present genetic and molecular evidence implicating RCI1A in the response to low temperature. Our results demonstrate that RCI1A functions as a negative regulator of constitutive freezing tolerance and cold acclimation in Arabidopsis thaliana by controlling cold-induced gene expression. Interestingly, this control is partially performed through an ethylene (ET) dependent pathway involving physical interaction with different ACC SYNTHASE (ACS) isoforms and a decreased ACS stability. We show that, consequently, RCI1A restrains ET biosynthesis, contributing to establish adequate levels of this hormone in Arabidopsis under both standard and low-temperature conditions. We further show that these levels are required to promote proper cold-induced gene expression and freezing tolerance before and after cold acclimation. All these data indicate that RCI1A connects the low-temperature response with ET biosynthesis to modulate constitutive freezing tolerance and cold acclimation in Arabidopsis. PMID- 25122151 TI - The ABC transporter ABCG1 is required for suberin formation in potato tuber periderm. AB - The lipid biopolymer suberin plays a major role as a barrier both at plant environment interfaces and in internal tissues, restricting water and nutrient transport. In potato (Solanum tuberosum), tuber integrity is dependent on suberized periderm. Using microarray analyses, we identified ABCG1, encoding an ABC transporter, as a gene responsive to the pathogen-associated molecular pattern Pep-13. Further analyses revealed that ABCG1 is expressed in roots and tuber periderm, as well as in wounded leaves. Transgenic ABCG1-RNAi potato plants with downregulated expression of ABCG1 display major alterations in both root and tuber morphology, whereas the aerial part of the ABCG1-RNAi plants appear normal. The tuber periderm and root exodermis show reduced suberin staining and disorganized cell layers. Metabolite analyses revealed reduction of esterified suberin components and hyperaccumulation of putative suberin precursors in the tuber periderm of RNA interference plants, suggesting that ABCG1 is required for the export of suberin components. PMID- 25122155 TI - Water-soluble and cleavable quercetin-amino acid conjugates as safe modulators for P-glycoprotein-based multidrug resistance. AB - Quercetin-amino acid conjugates with alanine or glutamic acid moiety attached at 7-O and/or 3-O position of quercetin were prepared, and their multidrug resistance (MDR)-modulatory effects were evaluated. A quercetin-glutamic acid conjugate, 7-O-Glu-Q (3a), was as potent as verapamil in reversing MDR and sensitized MDR MES-SA/Dx5 cells to various anticancer drugs with EC50 values of 0.8-0.9 MUM. Analysis on Rh-123 accumulation confirmed that 3a inhibits drug efflux by Pgp, and Pgp ATPase assay showed that 3a interacts with the drug binding site of Pgp to stimulate its ATPase activity. Physicochemical analysis of 3a revealed that solubility, stability, and cellular uptake of quercetin were significantly improved by the glutamic acid promoiety, which eventually dissociates from 3a to produce quercetin and quercetin metabolites in intracellular milieu. Taken together, potent MDR-modulating activity along with intracellular conversion into the natural flavonoid quercetin warrants development of the quercetin-amino acid conjugates as safe MDR modulators. PMID- 25122156 TI - Clinical audit: still an important tool for improving healthcare. AB - The use of data to challenge and improve healthcare has a long and distinguished history but has often failed to bring about expected improvements. It has never become fully embedded in clinical practice, probably because data alone are insufficient to drive change. There is now a greater appreciation that changing and improving healthcare requires changing behaviours. Clinical audit remains one of the important tools that can be used to facilitate such change. PMID- 25122153 TI - Comparative transcriptome atlases reveal altered gene expression modules between two Cleomaceae C3 and C4 plant species. AB - C(4) photosynthesis outperforms the ancestral C(3) state in a wide range of natural and agro-ecosystems by affording higher water-use and nitrogen-use efficiencies. It therefore represents a prime target for engineering novel, high yielding crops by introducing the trait into C(3) backgrounds. However, the genetic architecture of C(4) photosynthesis remains largely unknown. To define the divergence in gene expression modules between C(3) and C(4) photosynthesis during leaf ontogeny, we generated comprehensive transcriptome atlases of two Cleomaceae species, Gynandropsis gynandra (C(4)) and Tarenaya hassleriana (C(3)), by RNA sequencing. Overall, the gene expression profiles appear remarkably similar between the C(3) and C(4) species. We found that known C(4) genes were recruited to photosynthesis from different expression domains in C(3), including typical housekeeping gene expression patterns in various tissues as well as individual heterotrophic tissues. Furthermore, we identified a structure-related module recruited from the C(3) root. Comparison of gene expression patterns with anatomy during leaf ontogeny provided insight into genetic features of Kranz anatomy. Altered expression of developmental factors and cell cycle genes is associated with a higher degree of endoreduplication in enlarged C(4) bundle sheath cells. A delay in mesophyll differentiation apparent both in the leaf anatomy and the transcriptome allows for extended vein formation in the C(4) leaf. PMID- 25122157 TI - Practical pharmacokinetics: what do you really need to know? AB - Having some understanding of pharmacokinetics is important for all clinicians when prescribing medications. Key elements to effective and safe prescribing include making sure that we don't underdose a medication making it ineffective, but also do not overprescribe a treatment known to cause toxic effects. In paediatrics, there are significant physiological and developmental differences that add to the challenges of safe prescribing. This article aims to provide the clinician with some basic paediatric pharmacokinetic principles with clinical examples to aid their prescribing skills. PMID- 25122154 TI - Identification of a sphingolipid alpha-glucuronosyltransferase that is essential for pollen function in Arabidopsis. AB - Glycosyl inositol phosphorylceramide (GIPC) sphingolipids are a major class of lipids in fungi, protozoans, and plants. GIPCs are abundant in the plasma membrane in plants, comprising around a quarter of the total lipids in these membranes. Plant GIPCs contain unique glycan decorations that include a conserved glucuronic acid (GlcA) residue and various additional sugars; however, no proteins responsible for glycosylating GIPCs have been identified to date. Here, we show that the Arabidopsis thaliana protein INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE1 (IPUT1) transfers GlcA from UDP-GlcA to GIPCs. To demonstrate IPUT1 activity, we introduced the IPUT1 gene together with genes for a UDP-glucose dehydrogenase from Arabidopsis and a human UDP-GlcA transporter into a yeast mutant deficient in the endogenous inositol phosphorylceramide (IPC) mannosyltransferase. In this engineered yeast strain, IPUT1 transferred GlcA to IPC. Overexpression or silencing of IPUT1 in Nicotiana benthamiana resulted in an increase or a decrease, respectively, in IPC glucuronosyltransferase activity in vitro. Plants in which IPUT1 was silenced accumulated IPC, the immediate precursor, as well as ceramides and glucosylceramides. Plants overexpressing IPUT1 showed an increased content of GIPCs. Mutations in IPUT1 are not transmitted through pollen, indicating that these sphingolipids are essential in plants. PMID- 25122158 TI - Developing clinical guidelines: how much rigour is required? AB - Clinical guidelines that are rigorously developed play a fundamental role in improving healthcare and reducing unnecessary variations in practice. National guidelines are increasingly used by healthcare professionals, patients and commissioners; however, national bodies are unable to meet the demand for guidance on all topics. There are fewer resources available for guidance produced locally or by specialty groups, and it is necessary to achieve a balance between pragmatism and rigour while conforming to the widely accepted norms of what constitutes a good guideline. This paper introduces the key concepts around this topic with suggestions for those interested in developing their own guideline. An example of challenges encountered in generating high-quality clinical guidance is given in box 1. Box 1 Challenges in guideline development Professor Johnson runs a local developmental paediatrics service with eight other colleagues. All have different ways of managing children with PAVING syndrome. This was difficult for patients and staff and has led to disagreements on how certain patients should be managed. As a result, Professor Johnson developed a Guideline Development Group to look at the management of PAVING syndrome. The group identified 12 clinical questions (including diagnosis, exclusion of comorbidities, treatment modalities), searched the PubMed database and found some useful evidence that they used to formulate key recommendations. For one question about behavioural therapy, PubMed did not suggest any evidence so they informally arrived at a consensus among themselves and wrote up their guideline. On the back of this success, they applied for the guideline to be endorsed or supported by the Royal College of Paediatrics and Child Health (RCPCH). To their frustration, it was turned down on methodological grounds. Professor Johnson wrote to the RCPCH saying that he was "pretty peeved that the PAVING syndrome guideline had been rejected" for the College endorsement given all the work that had gone into writing it and "would the College mind being a bit more explicit in their guidance," to anyone who might consider doing this in the future? PMID- 25122159 TI - PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats. AB - In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARalpha expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARalpha expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARalpha ligand leukotriene B4 upregulated the expression of PPARalpha and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARalpha expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARalpha expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands. PMID- 25122160 TI - Structure of chitosan determines its interactions with mucin. AB - Synthetic and natural mucoadhesive biomaterials in optimized galenical formulations are potentially useful for the transmucosal delivery of active ingredients to improve their localized and prolonged effects. Chitosans (CS) have potent mucoadhesive characteristics, but the exact mechanisms underpinning such interactions at the molecular level and the role of the specific structural properties of CS remain elusive. In the present study we used a combination of microviscosimetry, zeta potential analysis, isothermal titration calorimetry (ITC) and fluorescence quenching to confirm that the soluble fraction of porcine stomach mucin interacts with CS in water or 0.1 M NaCl (at c < c*; relative viscosity, eta(rel), ~ 2.0 at pH 4.5 and 37 degrees C) via a heterotypic stoichiometric process significantly influenced by the degree of CS acetylation (DA). We propose that CS-mucin interactions are driven predominantly by electrostatic binding, supported by other forces (e.g., hydrogen bonds and hydrophobic association) and that the DA influences the overall conformation of CS and thus the nature of the resulting complexes. Although the conditions used in this model system are simpler than the typical in vivo environment, the resulting knowledge will enable the rational design of CS-based nanostructured materials for specific transmucosal drug delivery (e.g., for Helicobacter pylori stomach therapy). PMID- 25122161 TI - Transformation of the multidisciplinary diabetic foot clinic into a multidisciplinary diabetic foot day unit: results from a service evaluation. AB - The natural history of the diabetic foot is aggressive and complex. To counteract this, we describe the transformation of a Multidisciplinary Diabetic Foot Clinic into a Multidisciplinary Diabetic Foot Day Unit, which delivers an emergency open access system for patients, with a "one-stop," same day service in which investigations are performed, results reviewed and treatment implemented. It also provides joint clinics with vascular, orthopaedic, and plastic surgeons and specialized clinics for casting of complex neuropathic feet and for the administration of intravenous or intramuscular antibiotics on the same day. The aim was to document these increasingly wide-ranging facilities by undertaking a retrospective evaluation over a 6-week period, with analysis of notes, investigations, and an anonymous patient satisfaction survey. The clinic was visited by 597 patients who attended in 1076 appointments, of which 112 (10.4%) were emergency visits; these patients attended the clinic without a booked appointment but via an open access policy, 93 of whom were known to the clinic, but 19 were new self-referred patients to the service. Furthermore, 197 (18%) were seen in a Joint Vascular Diabetic Foot Clinic and 98 (9%) were seen in a Joint Orthopaedic Plastic Diabetic Foot Clinic, 570 (53%) were seen in an Active Ulcer Clinic and 97 (9%) in a Total Contact Casting Clinic. Forty-five percent of patients were prescribed antibiotics, including 188 (76%) as oral and 45(18%) as intravenous antibiotics and 15(6%) as intramuscular injections. Of the 1076 appointments, 150 (14%) patients were in the foot clinic for more than 4 hours. Sixty (10%) patients were reviewed 4 or more times over the 6-week period. Only 22 (2%) were admitted to hospital. Of the 125 survey responders, 98% were satisfied with this service, which has evolved from a Diabetic Foot Clinic into a Multidisciplinary Diabetic Foot Day Unit. PMID- 25122162 TI - Diltiazem for the management of malignancy-associated perineal pain and tenesmus. AB - BACKGROUND: Perineal pain is a frequent complaint of patients with advanced cancer (colorectal, genitourinary, prostate), and often quite difficult to manage with significant impact on quality of life. Calcium channel blockers (CCBs) are potent inhibitors of intestinal smooth muscle contraction and have been shown to impact tone and motility of the gastrointestinal tract. As such, they have been used in various pain syndromes of the lower gastrointestinal tract, such as chronic anal fissure, to promote healing and improve pain. Here we describe two cases using oral diltiazem for malignancy-associated perineal pain and tenesmus. DISCUSSION: The first case describes an elderly male with advanced urothelial cancer post surgical resection and chemoradiation who suffered from rectal pain described as "sitting on a football" despite nerve blocks and oral opioids. He experienced dramatic improvement in pain scores and daily requirements of oral analgesics after starting oral diltiazem. The second case describes a middle-aged female with rectal cancer post surgical resection and chemoradiation who suffered from quality-of-life-limiting rectal pain and pressure despite oral opioids. She experienced dramatic improvement in the "pressure-type" pain after adding oral diltiazem. CONCLUSION: Based on our experience with these two cases, we propose oral diltiazem for use as an adjunct therapy for management of chronic malignancy associated perineal pain, specifically with characteristics of pressure-type pain and tenesmus. PMID- 25122163 TI - Face mask sampling for the detection of Mycobacterium tuberculosis in expelled aerosols. AB - BACKGROUND: Although tuberculosis is transmitted by the airborne route, direct information on the natural output of bacilli into air by source cases is very limited. We sought to address this through sampling of expelled aerosols in face masks that were subsequently analyzed for mycobacterial contamination. METHODS: In series 1, 17 smear microscopy positive patients wore standard surgical face masks once or twice for periods between 10 minutes and 5 hours; mycobacterial contamination was detected using a bacteriophage assay. In series 2, 19 patients with suspected tuberculosis were studied in Leicester UK and 10 patients with at least one positive smear were studied in The Gambia. These subjects wore one FFP30 mask modified to contain a gelatin filter for one hour; this was subsequently analyzed by the Xpert MTB/RIF system. RESULTS: In series 1, the bacteriophage assay detected live mycobacteria in 11/17 patients with wearing times between 10 and 120 minutes. Variation was seen in mask positivity and the level of contamination detected in multiple samples from the same patient. Two patients had non-tuberculous mycobacterial infections. In series 2, 13/20 patients with pulmonary tuberculosis produced positive masks and 0/9 patients with extrapulmonary or non-tuberculous diagnoses were mask positive. Overall, 65% of patients with confirmed pulmonary mycobacterial infection gave positive masks and this included 3/6 patients who received diagnostic bronchoalveolar lavages. CONCLUSION: Mask sampling provides a simple means of assessing mycobacterial output in non-sputum expectorant. The approach shows potential for application to the study of airborne transmission and to diagnosis. PMID- 25122167 TI - The floods in China: report by the medical director of the health organisation on the work undertaken to co-ordinate the campaign against epidemics. PMID- 25122164 TI - Qishenyiqi protects ligation-induced left ventricular remodeling by attenuating inflammation and fibrosis via STAT3 and NF-kappaB signaling pathway. AB - AIM: Qi-shen-yi-qi (QSYQ), a formula used for the routine treatment of heart failure (HF) in China, has been demonstrated to improve cardiac function through down-regulating the activation of the Renin-Angiotensin-Aldosterone System (RAAS). However, the mechanisms governing its therapeutic effects are largely unknown. The present study aims to demonstrate that QSYQ treatment can prevent left ventricular remodeling in heart failure by attenuating oxidative stress and inhabiting inflammation. METHODS: Sprague-Dawley (SD) rats were randomly divided into 6 groups: sham group, model group (LAD coronary artery ligation), QSYQ group with high dosage, middle dosage and low dosage (LAD ligation and treated with QSYQ), and captopril group (LAD ligation and treated with captopril as the positive drug). Indicators of fibrosis (Masson, MMPs, and collagens) and inflammation factors were detected 28 days after surgery. RESULTS: Results of hemodynamic alterations (dp/dt value) in the model group as well as other ventricular remodeling (VR) markers, such as MMP-2, MMP-9, collagen I and III elevated compared with sham group. VR was accompanied by activation of RAAS (angiotensin II and NADPHoxidase). Levels of pro-inflammatory cytokines (TNF alpha, IL-6) in myocardial tissue were also up-regulated. Treatment of QSYQ improved cardiac remodeling through counter-acting the aforementioned events. The improvement of QSYQ was accompanied with a restoration of angiotensin II NADPHoxidase-ROS-MMPs pathways. In addition, "therapeutic" QSYQ administration can reduce both TNF-alpha-NF-B and IL-6-STAT3 pathways, respectively, which further proves the beneficial effects of QSYQ. CONCLUSIONS: Our study demonstrated that QSYQ protected LAD ligation-induced left VR via attenuating AngII -NADPH oxidase pathway and inhabiting inflammation. These findings provide evidence as to the cardiac protective efficacy of QSYQ to HF and explain the beneficial effects of QSYQ in the clinical application for HF. PMID- 25122165 TI - ATO/ATRA/anthracycline-chemotherapy sequential consolidation achieves long-term efficacy in primary acute promyelocytic leukemia. AB - The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3, ATO) has been effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but the long-term efficacy and safety among newly diagnosed APL patients are unclear. In this retrospective study, total 45 newly diagnosed APL patients received ATRA/chemotherapy combination regimen to induce remission. Among them, 43 patients (95.6%) achieved complete remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment with a median follow-up of 55 months. In these patients, the estimated overall survival (OS) and the relapse free survival (RFS) were 94.4% +/- 3.9% and 94.6 +/- 3.7%, respectively. The toxicity profile was mild and reversible. No secondary carcinoma was observed. These results demonstrated the high efficacy and minimal toxicity of ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for APL. PMID- 25122170 TI - Genetics and health communication: a primer. AB - The progress of genetic knowledge has been swift and steadfast. As we move forward in the genomic era, post Human Genome Project, and continue to explore how one's genes interact with one's environment, it becomes increasingly important for all audiences to have a firm grasp of the vocabulary used in this health context. This primer is intended to be used as a reference and to introduce and/or make more clear concepts related to genetics to increase understanding. PMID- 25122166 TI - In vitro and in vivo studies for assessing the immune response and protection inducing ability conferred by Fasciola hepatica-derived synthetic peptides containing B- and T-cell epitopes. AB - Fasciolosis is considered the most widespread trematode disease affecting grazing animals around the world; it is currently recognised by the World Health Organisation as an emergent human pathogen. Triclabendazole is still the most effective drug against this disease; however, resistant strains have appeared and developing an effective vaccine against this disease has increasingly become a priority. Several bioinformatics tools were here used for predicting B- and T cell epitopes according to the available data for Fasciola hepatica protein amino acid sequences. BALB/c mice were immunised with the synthetic peptides by using the ADAD vaccination system and several immune response parameters were measured (antibody titres, cytokine levels, T-cell populations) to evaluate their ability to elicit an immune response. Based on the immunogenicity results so obtained, seven peptides were selected to assess their protection-inducing ability against experimental infection with F. hepatica metacercariae. Twenty-four B- or T epitope-containing peptides were predicted and chemically synthesised. Immunisation of mice with peptides so-called B1, B2, B5, B6, T14, T15 and T16 induced high levels of total IgG, IgG1 and IgG2a (p<0.05) and a mixed Th1/Th2/Th17/Treg immune response, according to IFN-gamma, IL-4, IL-17 and IL-10 levels, accompanied by increased CD62L+ T-cell populations. A high level of protection was obtained in mice vaccinated with peptides B2, B5, B6 and T15 formulated in the ADAD vaccination system with the AA0029 immunomodulator. The bioinformatics approach used in the present study led to the identification of seven peptides as vaccine candidates against the infection caused by Fasciola hepatica (a liver-fluke trematode). However, vaccine efficacy must be evaluated in other host species, including those having veterinary importance. PMID- 25122171 TI - Post-processing in cardiovascular computed tomography: performance of a client server solution versus a stand-alone solution. AB - PURPOSE: To compare the performance of server-based (CSS) versus stand-alone post processing software (ES) for the evaluation of cardiovascular CT examinations (cvCT) and to determine the crucial steps. MATERIALS AND METHODS: Data of 40 patients (20 patients for coronary artery evaluation and 20 patients prior to transcatheter aortic valve implantation [TAVI]) were evaluated by 5 radiologists with CSS and ES. Data acquisition was performed using a dual-source 128-row CT unit (SOMATOM Definition Flash, Siemens, Erlangen, Germany) and a 64-row CT unit (Brilliance 64, Philips, Hamburg, Germany). The following workflow was evaluated: Data loading, aorta and coronary segmentation, curved multiplanar reconstruction (cMPR) and 3 D volume rendering technique (3D-VRT), measuring of coronary artery stenosis and planimetry of the aortic annulus. The time requirement and subjective quality for the workflow were evaluated. RESULTS: The coronary arteries as well as the TAVI data could be evaluated significantly faster with CSS (5.5 +/- 2.9 min and 8.2 +/- 4.0 min, respectively) than with ES (13.9 +/- 5.2 min and 15.2 +/- 10.9 min, respectively, p <= 0.01). Segmentation of the aorta (CSS: 1.9 +/- 2.0 min, ES: 3.7 +/- 3.3 min), generating cMPR of coronaries (CSS: 0.5 +/- 0.2 min, ES: 5.1 +/- 2.6 min), aorta and iliac vessels (CSS: 0.5 +/- 0.4 min and 0.4 +/- 0.4 min, respectively, ES: 1.6 +/- 0.7 min and 2.8 +/- 3 min, respectively) could be performed significantly faster with CSS than with ES with higher quality of cMPR, measuring of coronary stenosis and 3D-VRT (p < 0.05). CONCLUSION: Evaluation of cvCT can be accomplished significantly faster and better with CSS than with ES. The segmentation remains the most time-consuming workflow step, so optimization of segmentation algorithms could improve performance even further. PMID- 25122172 TI - The role of volume perfusion CT in the diagnosis of pathologies of the pancreas. AB - The review discusses the potential role of volume perfusion CT (VPCT) in the diagnosis and follow-up of different pathologies of the pancreas. VPCT enables a differentiation of different pancreatic tumors like adenocarcinoma or neuroendocrine tumors based on functional parameters like blood flow, blood volume and permeability. Furthermore, the article discusses the potential indications for VPCT imaging of inflammatory diseases of the pancreas such as acute or chronic pancreatitis and autoimmune pancreatitis. PMID- 25122173 TI - Radiological evaluation of the therapeutic response of malignant diseases: status quo, innovative developments and requirements for radiology. AB - In consequence of the rapid development of newer targeted and personalized tumor therapies, radiology as an essential component of the treatment concept of numerous malignant diseases needs to improve in order to adequately capture and evaluate the effects, but also the side effects of these novel therapeutic agents. The early recognition of therapy response or failure is crucial for the optimal planning of the further treatment and can therefore have direct impact on the chances of recovery and the survival time of oncological patients. In previous years, the goal of medical imaging was to just qualitatively assess the increase or reduction in the size of tumors and their metastases, which was often achieved by a simple subjective estimation of the tumor findings by the diagnosing radiologist. Nowadays, radiology is faced with the challenge of evaluating changes during therapy quantitatively and of visualizing therapeutic effects that are more discrete (e. g. necrosis, altered tumor perfusion). The importance of an adequate assessment of therapy response is further underlined by the fact that in these days, a good portion of oncological patients are enrolled in clinical trials, in which the quantitative radiological evaluation of malignant disorders is an important surrogate parameter. On the basis of this development, the demands for radiology to provide more sophisticated assessments of therapy response and documentation of imaging findings have been constantly growing. The following article provides an overview of the established and still widely spread but in particular also the latest imaging modalities and evaluation criteria with regard to oncological diseases as well as of the increasing demands on radiology that result from these developments. Beyond that, future advancements in tumor imaging are taken into account and the new challenges these developments will bring are discussed. KEY POINTS: * In the era of personalized medicine, evaluation criteria that are individually adapted to the respective patient are required.* Radiology needs to substantially contribute to oncological treatment concepts and the evaluation of therapeutic response. PMID- 25122175 TI - [A rare complication of pulmonary tuberculosis - Rasmussen aneurysm - radiologic diagnosis and therapy]. PMID- 25122174 TI - S3 guideline for chronic pancreatitis - diagnosis, classification and therapy for the radiologist. AB - Chronic pancreatitis shows an increasing prevalence and incidence mainly in the Western Hemisphere. Early diagnosis and therapy are frequently delayed because of non-specific symptoms as well as non-specific blood values. The German Society of Digestive and Metabolic Diseases (DGVS) organized the preparation and publication of an interdisciplinary S3 level guideline with the support of the German Radiological Society (DRG) as 1 of 11 contributing societies. In this article we present and discuss the main topics of the guideline regarding the diagnosis, differential diagnosis and therapy of complications of this complex chronic disease with a focus on clinical and scientific radiologists. KEY POINTS: * Ultarsound represents the perfect first line imaging modality * For further diagnostic werk up MRI with MRCP are recommended for the differential diagnosis of pancreatic cancer * For clinical studies the modified (CT, MRI) Cambridge classification is recommended. PMID- 25122176 TI - [A rare complication: acute ischemic stomach necrosis within the scope of non occlusive mesenteric ischemia (NOMI)]. PMID- 25122177 TI - [Contrast medium going astray]. PMID- 25122178 TI - [Chronic adhesive small intestine volvulus in adulthood, a rare disease picture]. PMID- 25122179 TI - [Osteolytic behavior of a growing tumor of the calvarium: rare differential intraosseous meningioma diagnosis]. PMID- 25122180 TI - A systematic review of scope and quality of health economic evaluation studies in Vietnam. AB - INTRODUCTION: The application of health economic evaluation (HEE) evidence can play an important role in strategic planning and policy making. This study aimed to assess the scope and quality of existing research, with the goal of elucidating implications for improving the use of HEE evidence in Vietnam. METHODS: A comprehensive search strategy was developed to search medical online databases (Medline, Google Scholar, and Vietnam Medical Databases) to select all types of HEE studies except cost-only analyses. Two researchers assessed the quality of selected studies using the Quality of Health Economic Studies (QHES) instrument. RESULTS: We selected 26 studies, including 6 published in Vietnam. The majority of these studies focused on infectious diseases (14 studies), with HIV being the most common topic (5 studies). Most papers were cost-effectiveness studies that measured health outcomes using DALY units. Using QHES, we found that the overall quality of HEE studies published internationally was much higher (mean score 88.7+13.3) than that of those published in Vietnam (mean score 67.3+22.9). Lack of costing perspectives, reliable data sources and sensitivity analysis were the main shortcomings of the reviewed studies. CONCLUSION: This review indicates that HEE studies published in Vietnam are limited in scope and number, as well as by several important technical errors or omissions. It is necessary to formalize the process of health economic research in Vietnam and to institutionalize the links between researchers and policy-makers. Additionally, the quality of HEE should be enhanced through education about research techniques, and the implementation of standard HEE guidelines. PMID- 25122181 TI - Multivitamin and protein supplement use is associated with positive mood states and health behaviors in US Military and Coast Guard personnel. AB - Approximately 60% of Armed Forces personnel regularly consume dietary supplements (DSs). We investigated the association of mood and health behaviors with multiple classes of DSs in military and Coast Guard personnel (N = 5536). Participants completed a survey of DS use and the Quick Mood Scale to assess mood domains of wakeful-drowsiness, relaxed-anxious, cheerful-depressed, friendly-aggression, clearheaded-confused, and well coordinated-clumsy. Supplements were categorized as multivitamin/minerals (MVM), individual vitamin/minerals, protein/amino acid supplements (PS), combination products (C), herbals (H), purported steroid analogs, (S) and other (O). One-way analyses of covariance assessed associations of DSs and perceived health behavior with mood controlling for age. Logistic regression determined associations between DS use and health behavior. Users of MVM and PS reported feeling significantly (P < 0.05) more awake, relaxed, cheerful, clearheaded, and coordinated. Participants using PS and S reported feeling less friendly (more aggressive, P < 0.02). Users of MVM and PS were more likely to report their general health, eating habits, and fitness level as excellent/good (P < 0.05). Participants reporting health behaviors as excellent/good were more (P < 0.01) awake, relaxed, cheerful, friendly, clearheaded, and coordinated. As no known biological mechanisms can explain such diverse effects of MVM and PS use on multiple mood states, health, eating habits, and fitness, we hypothesize these associations are not causal, and DS intake does not alter these parameters per se. Preexisting differences in mood and other health-related behaviors and outcomes between users versus nonusers of DSs could be a confounding factor in studies of DSs. PMID- 25122182 TI - MicroRNA-30e* suppresses dengue virus replication by promoting NF-kappaB dependent IFN production. AB - MicroRNAs have been shown to contribute to a repertoire of host-pathogen interactions during viral infection. Our previous study demonstrated that microRNA-30e* (miR-30e*) directly targeted the IkappaBalpha 3'-UTR and disrupted the NF-kappaB/IkappaBalpha negative feedback loop, leading to hyperactivation of NF-kappaB. This current study investigated the possible role of miR-30e* in the regulation of innate immunity associated with dengue virus (DENV) infection. We found that DENV infection could induce miR-30e* expression in DENV-permissive cells, and such an overexpression of miR-30e* upregulated IFN-beta and the downstream IFN-stimulated genes (ISGs) such as OAS1, MxA and IFITM1, and suppressed DENV replication. Furthermore, suppression of IkappaBalpha mediates the enhancing effect of miR-30e* on IFN-beta-induced antiviral response. Collectively, our findings suggest a modulatory role of miR-30e* in DENV induced IFN-beta signaling via the NF-kappaB-dependent pathway. Further investigation is needed to evaluate whether miR-30e* has an anti-DENV effect in vivo. PMID- 25122184 TI - Rape in war: how a US law prevents aid for safe abortions. PMID- 25122183 TI - Mannosylation of virus-like particles enhances internalization by antigen presenting cells. AB - Internalization of peptides by antigen presenting cells is crucial for the initiation of the adaptive immune response. Mannosylation has been demonstrated to enhance antigen uptake through mannose receptors, leading to improved immune responses. In this study we test the effect of surface mannosylation of protein based virus-like particles (VLP) derived from Rabbit hemorrhagic disease virus (RHDV) on uptake by murine and human antigen presenting cells. A monomannoside and a novel dimannoside were synthesized and successfully conjugated to RHDV VLP capsid protein, providing approximately 270 mannose groups on the surface of each virus particle. VLP conjugated to the mannoside or dimannoside exhibited significantly enhanced binding and internalization by murine dendritic cells, macrophages and B cells as well as human dendritic cells and macrophages. This uptake was inhibited by the inclusion of mannan as a specific inhibitor of mannose specific uptake, demonstrating that mannosylation of VLP targets mannose receptor-based uptake. Consistent with mannose receptor-based uptake, partial retargeting of the intracellular processing of RHDV VLP was observed, confirming that mannosylation of VLP provides both enhanced uptake and modified processing of associated antigens. PMID- 25122187 TI - All of the above: When multiple correct response options enhance the testing effect. AB - Previous research has shown that multiple choice tests often improve memory retention. However, the presence of incorrect lures often attenuates this memory benefit. The current research examined the effects of "all of the above" (AOTA) options. When such options are correct, no incorrect lures are present. In the first three experiments, a correct AOTA option on an initial test led to a larger memory benefit than no test and standard multiple choice test conditions. The benefits of a correct AOTA option occurred even without feedback on the initial test; for both 5-minute and 48-hour retention delays; and for both cued recall and multiple choice final test formats. In the final experiment, an AOTA question led to better memory retention than did a control condition that had identical timing and exposure to response options. However, the benefits relative to this control condition were similar regardless of the type of multiple choice test (AOTA or not). Results suggest that retrieval contributes to multiple choice testing effects. However, the extra testing effect from a correct AOTA option, rather than being due to more retrieval, might be due simply to more exposure to correct information. PMID- 25122185 TI - A nationwide study of SLE in Japanese identified subgroups of patients with clear signs patterns and associations between signs and age or sex. AB - We performed a nationwide study to determine the distributions of the signs and clinical markers of systemic lupus erythematosus (SLE) and identify any patterns in their distributions to allow patient subclassification. We obtained 256,999 patient-year records describing the disease status of SLE patients from 2003 to 2010. Of these, 14,779 involved patients diagnosed within the last year, and 242,220 involved patients being followed up. Along with basic descriptive statistics, we analyzed the effects of sex, age and disease duration on the frequencies of signs in the first year and follow-up years. The patients and major signs were clustered using the Ward method. The female patients were younger at onset. Renal involvement and discoid eczema were more frequent in males, whereas arthritis, photosensitivity and cytopenia were less. Autoantibody production and malar rash were positively associated with young age, and serositis and arthritis were negatively associated. Photosensitivity was positively associated with a long disease duration, and autoantibody production, serositis and cytopenia were negatively associated. The SLE patients were clustered into subgroups, as were the major signs. We identified differences in SLE clinical features according to sex, age and disease duration. Subgroups of SLE patients and the major signs of SLE exist. PMID- 25122188 TI - Ovarian stimulation using human chorionic gonadotrophin impairs blastocyst implantation and decidualization by altering ovarian hormone levels and downstream signaling in mice. AB - Ovarian stimulation induced by follicle-stimulating hormone and human chorionic gonadotrophin (hCG) is commonly used in assisted reproductive technology to increase embryo production. However, recent clinical and animal studies have shown that ovarian stimulation disrupts endometrial function and embryo development and adversely affects pregnancy outcomes. How ovarian stimulation impairs pregnancy establishment and the precise mechanisms by which this stimulation reduces the chances of conception remain unclear. In this study, we first demonstrated that ovarian stimulation using hCG alone impairs implantation, decidualization and fetal development of mice by generating abnormal ovarian hormone levels. We also showed that ovarian hormone levels were altered because of changes in the levels of the enzymes involved in their synthesis in the follicles and corpora lutea. Furthermore, we determined that anomalous ovarian hormone secretion induced by ovarian stimulation alters the spatiotemporal expression of progesterone receptors and their downstream genes, especially in the uterine epithelium. Epithelial estrogenic signaling and cell proliferation were promoted on the day of implantation in stimulated mice and these changes led to the failure of uterine transition from the prereceptive to the receptive state. Collectively, our findings indicate that ovarian stimulation using hCG induces an imbalance in steroid hormone secretion, which causes a failure of the development of uterine receptivity and subsequent implantation and decidualization by altering the expression of steroid receptors and their downstream signaling associated with embryo implantation. PMID- 25122186 TI - Cardiac structure and function and prognosis in heart failure with preserved ejection fraction: findings from the echocardiographic study of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial. AB - BACKGROUND: Abnormalities in cardiac structure and function in heart failure with preserved ejection fraction may help identify patients at particularly high risk for cardiovascular morbidity and mortality. METHODS AND RESULTS: Cardiac structure and function were assessed by echocardiography in a blinded core laboratory at baseline in 935 patients with heart failure with preserved ejection fraction (left ventricular ejection fraction >=45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial and related to the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest, and its components. At a median follow-up of 2.9 years, 244 patients experienced the primary outcome. Left ventricular hypertrophy (adjusted hazard ratio, 1.52; 95% confidence interval, 1.16-2.00), elevated left ventricular filling pressure (E/E'; adjusted hazard ratio 1.05 per 1 integer increase; 95% confidence interval, 1.02-1.07), and higher pulmonary artery pressure assessed by the tricuspid regurgitation velocity (hazard ratio, 1.23 per 0.5 m/s increase; 95% confidence interval, 1.02-1.49) were associated with the composite outcome and heart failure hospitalization alone after adjusting for clinical and laboratory variables. The risk of adverse outcome associated with left ventricular hypertrophy was additive to the risk associated with elevated E/E'. CONCLUSIONS: Among heart failure with preserved ejection fraction patients enrolled in TOPCAT, left ventricular hypertrophy, higher left ventricular filling pressure, and higher pulmonary artery pressure were predictive of heart failure hospitalization, cardiovascular death, or aborted cardiac arrest independent of clinical and laboratory predictors. These features, both alone and in combination, identify heart failure with preserved ejection fraction patients at particularly high risk for cardiovascular morbidity and mortality. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302. PMID- 25122190 TI - Dual-channel-mediated spin coupling for one-electron-oxidized cobalt(II)-saddled porphyrin. AB - Saddle-shaped Co(II)[OET(p-R)PP] (R = CF3, H, CH3) can be readily oxidized with Cl2, Br2, and I2 to the corresponding one-electron-oxidation product Co[OET(p R)PP]X (X = Cl, Br, I) with the clear character of a ring cation radical. With the series of (1)H and (13)C NMR spectra of these related complexes, both the axial ligand and peripheral substituent of the ring macrocycle are proven to act as a dual channel to tune spin coupling between low-spin Co(II) and a porphyrin pi-cation radical. Density functional theory calculations have shown that the antiferromagnetic coupling between spins residing in d(z)(2) and a(2u) are expected to exist as the ground state. The paramagnetic properties are attributed to an a(1u)-type ferromagnetic excited triplet state. PMID- 25122189 TI - Treatment selections using risk-benefit profiles based on data from comparative randomized clinical trials with multiple endpoints. AB - In a typical randomized clinical study to compare a new treatment with a control, oftentimes each study subject may experience any of several distinct outcomes during the study period, which collectively define the "risk-benefit" profile. To assess the effect of treatment, it is desirable to utilize the entirety of such outcome information. The times to these events, however, may not be observed completely due to, for example, competing risks or administrative censoring. The standard analyses based on the time to the first event, or individual component analyses with respect to each event time, are not ideal. In this paper, we classify each patient's risk-benefit profile, by considering all event times during follow-up, into several clinically meaningful ordinal categories. We first show how to make inferences for the treatment difference in a two-sample setting where categorical data are incomplete due to censoring. We then present a systematic procedure to identify patients who would benefit from a specific treatment using baseline covariate information. To obtain a valid and efficient system for personalized medicine, we utilize a cross-validation method for model building and evaluation and then make inferences using the final selected prediction procedure with an independent data set. The proposal is illustrated with the data from a clinical trial to evaluate a beta-blocker for treating chronic heart failure patients. PMID- 25122192 TI - Inner and outer portions of colonic circular muscle: ultrastructural and immunohistochemical changes in rat chronically treated with otilonium bromide. AB - Rat colonic circular muscle, main target of otilonium bromide (OB) spasmolytic activity, is subdivided in an inner and outer portion. Since the inner one is particularly rich in organelles involved in calcium availability (caveolae, smooth endoplasmic reticulum, mitochondria), the expression of specific markers (Caveolin-1, eNOS, calreticulin, calsequestrin) in comparison with the outer portion was investigated. The possible changes of these organelles and related markers, and of muscarinic receptors (Mr2) were then studied after OB chronic exposition. Rats were treated with 2-20 mg/kg/OB for 10 or 30 days. Proximal colon was processed by electron microscopy, immunohistochemistry, and western blot. In colon strips the stimulated contractility response to muscarinic agonist was investigated. The inner portion showed a higher expression of Caveolin-1 and Mr2, but not of eNOS, calreticulin and calsequestrin, compared to the outer portion. Chronic OB treatment caused similar ultrastructural and immunohistochemical changes in both portions. Organelles and some related markers were increased at 10 days; Mr2 expression and muscle contractility induced by methacholine was increased at 30 days. The present findings: 1) provide new information on the immunohistochemical properties of the inner portion of the circular layer that are in favour of a role it might play in colonic motility distinct from that of the outer portion; 2) demonstrate that chronically administered OB interferes with cell structures and molecules responsible for calcium handling and storage, and modifies cholinergic transmission. In conclusion, chronic OB administration in the colonic circular muscle layer directly interacts with the organelles and molecules calcium-related and with the Mr2. PMID- 25122194 TI - Regulating new psychoactive drugs: innovation leading to compromise. PMID- 25122195 TI - Graphene in the aquatic environment: adsorption, dispersion, toxicity and transformation. AB - Graphene-family nanomaterials (GFNs) including pristine graphene, reduced graphene oxide (rGO) and graphene oxide (GO) offer great application potential, leading to the possibility of their release into aquatic environments. Upon exposure, graphene/rGO and GO exhibit different adsorption properties toward environmental adsorbates, thus the molecular interactions at the GFN-water interface are discussed. After solute adsorption, the dispersion/aggregation behaviors of GFNs can be altered by solution chemistry, as well as by the presence of colloidal particles and biocolloids. GO has different dispersion performance from pristine graphene and rGO, which is further demonstrated from surface properties. Upon exposure in aquatic environments, GFNs have adverse impacts on aquatic organisms (e.g., bacteria, algae, plants, invertebrates, and fish). The mechanisms of GFNs toxicity at the cellular level are reviewed and the remaining unclear points on toxic mechanisms such as membrane damage are presented. Moreover, we highlight the transformation routes of GO to rGO. The degradation of GFNs upon exposure to UV irradiation and/or biota is also reviewed. In view of the unanswered questions, future research should include comprehensive characterization of GFNs, new approaches for explaining GFNs aggregation, environmental behaviors of metastable GO, and the relationship between dispersion of GFNs and the related adsorption properties. PMID- 25122199 TI - Prevalence of chronic skin and musculoskeletal conditions, United States-1969. AB - During 1969 the prevalence of chronic skin ,and musculoskeletal diseases among members of the civilian noninstitutionalized population was measured in the Health Interview Survey. Prevalence estimates and measures of impact of these conditions on the population covered by the Survey are presented in this report. This is the first report on the prevalence of chronic skin and musculoskeletal conditions based on data collected in health interviews to be published in the series, Vital and Health Statistics, and is one in a series of reports on specific condition groups (Series 10, Nos. 83,84, and 94). Methodological studies have shown that chronic conditions are generally underreported in interview surveys. Respondents in health interviews can report only those conditions of which they are aware and which they are willing to report to the interviewer. Reporting is better for those conditions which have made an impact on the affected individual and his family. Conditions that are severe, costly, or require treatment tend to be better reported than conditions having lesser impact. For instance, a condition which has caused hospitalization, limitation of activity, visits to the doctor, or days in bed is more likely to be reported in the interview than a condition which has little or no impact on the person. PMID- 25122196 TI - Epithelial and stromal microRNA signatures of columnar cell hyperplasia linking Let-7c to precancerous and cancerous breast cancer cell proliferation. AB - Columnar cell hyperplasia (CCH) is the earliest histologically identifiable breast lesion linked to cancer progression and is characterized by increased proliferation, decreased apoptosis and elevated oestrogen receptor alpha (ERalpha) expression. The mechanisms underlying the initiation of these lesions have not been clarified but might involve early and fundamental changes in cancer progression. MiRNAs are key regulators of several biological processes, acting by influencing the post-transcriptional regulation of numerous targets, thus making miRNAs potential candidates in cancer initiation. Here we have defined novel epithelial as well as stromal miRNA signatures from columnar cell hyperplasia lesions compared to normal terminal duct lobular units by using microdissection and miRNA microarrays. Let-7c were among the identified downregulated epithelial miRNAs and its functions were delineated in unique CCH derived cells and breast cancer cell line MCF-7 suggesting anti-proliferative traits potentially due to effects on Myb and ERalpha. MiR-132 was upregulated in the stroma surrounding CCH compared to stoma surrounding normal terminal duct lobular units (TDLUs), and overexpression of miR-132 in immortalized fibroblasts and in fibroblasts co cultured with epithelial CCH cells caused substantial expression changes of genes involved in metabolism, DNA damage and cell motility. The miRNA signatures identified in CCH indicate early changes in the epithelial and stromal compartment of CCH and could represent early key alterations in breast cancer progression that potentially could be targeted in novel prevention or treatment schedules. PMID- 25122200 TI - Adult stroke risk after growth hormone treatment in childhood: first do no harm. PMID- 25122193 TI - Global genetic variations predict brain response to faces. AB - Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ~ 500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40-50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R(2) = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R(2) = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co opting these regions into the face network. PMID- 25122197 TI - Increased generation of HIV-1 gp120-reactive CD8+ T cells by a DNA vaccine construct encoding the chemokine CCL3. AB - DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody derived single chain Fragment variable (scFv) specific for the major histocompatibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8+ T cells compared to non targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation. PMID- 25122201 TI - Bulbar muscle MRI changes in patients with SMA with reduced mouth opening and dysphagia. AB - OBJECTIVE: We performed a study in patients with proximal spinal muscular atrophy (SMA) to determine the prevalence of reduced maximal mouth opening (MMO) and its association with dysphagia as a reflection of bulbar dysfunction and visualized the underlying mechanisms using MRI. METHODS: We performed a cross-sectional study of MMO in 145 patients with SMA types 1-4 and 119 healthy controls and used MRI in 12 patients to visualize mandibular condylar shape and sliding and the anatomy of muscle groups relevant for mouth opening and closing. We analyzed associations of reduced MMO with SMA severity and complaints of dysphagia. RESULTS: Reduced MMO was defined as an interincisal distance <= 35 mm and was found in none of the healthy controls and in 100%, 79%, 50%, and 7% of patients with SMA types 1, 2, 3a, and 3b/4, respectively. MRI showed severe fatty degeneration of the lateral pterygoid muscles that mediate mouth opening by allowing mandibular condylar sliding but relatively mild involvement of the mouth closing muscles in patients with reduced MMO. Reduced MMO was associated with SMA type, age, muscle weakness, and dysphagia (p < 0.05). CONCLUSIONS: Reduced MMO is common in SMA types 1-3a and is mainly caused by fatty degeneration of specific mouth opening muscles. Reduced MMO is a sign of bulbar dysfunction in SMA. PMID- 25122198 TI - The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. AB - TMPRSS2 is an androgen-regulated cell-surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastases. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries, we identified a spectrum of TMPRSS2 substrates that include pro hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-MET receptor tyrosine kinase signaling, and initiated a proinvasive epithelial-to-mesenchymal transition phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment. SIGNIFICANCE: The vast majority of prostate cancer deaths are due to metastasis. Loss of TMPRSS2 activity dramatically attenuated the metastatic phenotype through mechanisms involving the HGF-c-MET axis. Therapeutic approaches directed toward inhibiting TMPRSS2 may reduce the incidence or progression of metastasis in patients with prostate cancer. PMID- 25122202 TI - Aspirin for secondary prevention after stroke of unknown etiology in resource limited settings. AB - OBJECTIVE: To analyze the potential impact of aspirin therapy for long-term secondary prevention after stroke of undetermined etiology in resource-limited settings without access to neuroimaging to distinguish ischemic stroke from intracerebral hemorrhage (ICH). METHODS: We conducted a decision analysis using a Markov state transition model. Sensitivity analyses were performed across the worldwide reported range of the proportion of strokes due to ICH and the 95% confidence intervals (CIs) of aspirin-associated relative risks in patients with ICH. RESULTS: For patients with stroke of undetermined etiology, long-term aspirin was the preferred treatment strategy across the worldwide reported range of the proportion of strokes due to ICH. At 34% of strokes due to ICH (the highest proportion reported in a large epidemiologic study), the benefit of aspirin remained beyond the upper bounds of the 95% CIs of aspirin-associated post-ICH relative risks most concerning to clinicians (ICH recurrence risk and mortality risk if ICH recurs on aspirin). Based on the estimated 11,590,204 strokes in low- and middle-income countries in 2010, our model predicts that aspirin therapy for secondary stroke prevention in all patients with stroke in these countries could lead to an estimated yearly decrease of 84,492 recurrent strokes and 4,056 stroke-related mortalities. CONCLUSIONS: The concern that the risks of aspirin in patients with stroke of unknown etiology could outweigh the benefits is not supported by our model, which predicts that aspirin for secondary prevention in patients with stroke of undetermined etiology in resource-limited settings could lead to decreased stroke-related mortality and stroke recurrence. PMID- 25122204 TI - Population-based incidence and prevalence of facioscapulohumeral dystrophy. AB - OBJECTIVE: To determine the incidence and prevalence of facioscapulohumeral muscular dystrophy (FSHD) in the Netherlands. METHODS: Using 3-source capture recapture methodology, we estimated the total yearly number of newly found symptomatic individuals with FSHD, including those not registered in any of the 3 sources. To this end, symptomatic individuals with FSHD were available from 3 large population-based registries in the Netherlands if diagnosed within a 10 year period (January 1, 2001 to December 31, 2010). Multiplication of the incidence and disease duration delivered the prevalence estimate. RESULTS: On average, 52 people are newly diagnosed with FSHD every year. This results in an incidence rate of 0.3/100,000 person-years in the Netherlands. The prevalence rate was 12/100,000, equivalent to 2,000 affected individuals. CONCLUSIONS: We present population-based incidence and prevalence estimates regarding symptomatic individuals with FSHD, including an estimation of the number of symptomatic individuals not present in any of the 3 used registries. This study shows that the total number of symptomatic persons with FSHD in the population may well be underestimated and a considerable number of affected individuals remain undiagnosed. This suggests that FSHD is one of the most prevalent neuromuscular disorders. PMID- 25122203 TI - The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia. AB - OBJECTIVE: To assess the clinical spectrum of ataxia-telangiectasia (A-T) in adults, with a focus on movement disorders. METHODS: A total of 14 consecutive adults with A-T were included at 2 tertiary adult movement disorders centers and compared to 53 typical patients with A-T. Clinical evaluation, neurophysiologic and video-oculographic recording, imaging, laboratory investigations, and ATM analysis were performed. RESULTS: In comparison with typical A-T cases, our patients demonstrated later mean age at onset (6.1 vs 2.5 years, p < 0.0001), later loss of walking ability (p = 0.003), and longer survival (p = 0.0039). The presenting feature was ataxia in 71% and dysarthria and dystonia in 14% each. All patients displayed movement disorders, among which dystonia and subcortical myoclonus were the most common (86%), followed by tremor (43%). Video oculographic recordings revealed mostly dysmetric saccades and 46% of patients had normal latencies (i.e., no oculomotor apraxia) and velocities. The alpha fetoprotein (AFP) level was normal in 7%, chromosomal instability was found in 29% (vs 100% of typical patients, p = 0.0006), and immunoglobulin deficiency was found in 29% (vs 69%, p = 0.057). All patients exhibited 2 ATM mutations, including at least 1 missense mutation in 79% of them (vs 36%, p = 0.0067). CONCLUSION: There is great variability of phenotype and severity in A-T, including a wide spectrum of movement disorders. Karyotype and repeated AFP level assessments should be performed in adults with unexplained movement disorders as valuable clues towards the diagnosis. In case of a compatible phenotype, A-T should be considered even if age at onset is late and progression is slow. PMID- 25122205 TI - Increased risk of osteoporosis in patients with myasthenia gravis: a population based cohort study. AB - OBJECTIVE: To determine the risk of osteoporosis in patients with myasthenia gravis (MG) in a large cohort representing 99% of the population of Taiwan. METHODS: Data from the Taiwan National Health Insurance Research Database were used to conduct retrospective cohort analyses. The study cohort consisted of 2,073 patients with MG who were 3-fold frequency-matched by age and sex and assigned the same index year as a comparison cohort without MG. Cox proportional hazard regression analysis was conducted to estimate the risk of osteoporosis. RESULTS: The MG cohort had a 1.96-fold increased risk of developing osteoporosis compared with the comparison cohort (hazard ratio [HR] = 1.96, 95% confidence interval [CI] = 1.57-2.44). Patients with MG older than 30 years developed an increased risk of osteoporosis, with the highest risk in the age group from 30 to 44 years, compared with the control cohort. Corticosteroid-naive patients with MG had a 1.52-fold increased risk of developing osteoporosis (HR = 1.52, 95% CI = 1.11-2.08), and the corticosteroid-treated cohort had a 2.37-fold increased risk of developing osteoporosis (HR = 2.37, 95% CI = 1.82-3.07). CONCLUSION: This population-based retrospective cohort study provides evidence that MG is associated with a high risk of osteoporosis regardless of corticosteroid use. PMID- 25122206 TI - Growth hormone treatment for childhood short stature and risk of stroke in early adulthood. AB - OBJECTIVES: We investigated the incidence of stroke and stroke subtypes in a population-based cohort of patients in France treated with growth hormone (GH) for short stature in childhood. METHODS: Adult morbidity data were obtained in 2008-2010 for 6,874 children with idiopathic isolated GH deficiency or short stature who started GH treatment between 1985 and 1996. Cerebrovascular events were validated using medical reports and imaging data and classified according to standard definitions of subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke. Case ascertainment completeness was estimated with capture recapture methods. The incidence of stroke and of stroke subtypes was calculated and compared with population values extracted from registries in Dijon and Oxford, between 2000 and 2012. RESULTS: Using both Dijon and Oxford population based registries as references, there was a significantly higher risk of stroke among patients treated with GH in childhood. The excess risk of stroke was mainly attributable to a very substantially and significantly higher risk of hemorrhagic stroke (standardized incidence ratio from 3.5 to 7.0 according to the registry rates considered, and accounting or not accounting for missed cases), and particularly subarachnoid hemorrhage (standardized incidence ratio from 5.7 to 9.3). CONCLUSIONS: We report a strong relationship between hemorrhagic stroke and GH treatment in childhood for isolated growth hormone deficiency or childhood short stature. Patients treated with GH worldwide should be advised about this association and further studies should evaluate the potentially causal role of GH treatment in these findings. PMID- 25122207 TI - Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis. AB - OBJECTIVE: We investigated a large sample of patients with amyotrophic lateral sclerosis (ALS) at rest in order to assess the value of (18)F-2-fluoro-2-deoxy-d glucose ((18)F-FDG) PET as a biomarker to discriminate patients from controls. METHODS: A total of 195 patients with ALS and 40 controls underwent brain (18)F FDG-PET, most within 5 months of diagnosis. Spinal and bulbar subgroups of ALS were also investigated. Twenty-five bilateral cortical and subcortical volumes of interest and cerebellum were taken into account, and (18)F-FDG uptakes were individually normalized by whole-brain values. Group analyses investigated the ALS-related metabolic changes. Discriminant analysis investigating sensitivity and specificity was performed using the 51 volumes of interest as well as age and sex. Metabolic connectivity was explored by voxel-wise interregional correlation analysis. RESULTS: Hypometabolism was found in frontal, motor, and occipital cortex and hypermetabolism in midbrain, temporal pole, and hippocampus in patients with ALS compared to controls. A similar metabolic pattern was also found in the 2 subgroups. Discriminant analysis showed a sensitivity of 95% and a specificity of 83% in separating patients from controls. Connectivity analysis found a highly significant positive correlation between midbrain and white matter in corticospinal tracts in patients with ALS. CONCLUSIONS: (18)F-FDG distribution changes in ALS showed a clear pattern of hypometabolism in frontal and occipital cortex and hypermetabolism in midbrain. The latter might be interpreted as the neurobiological correlate of diffuse subcortical gliosis. Discriminant analysis resulted in high sensitivity and specificity in differentiating patients with ALS from controls. Once validated by diseased-control studies, the present methodology might represent a potentially useful biomarker for ALS diagnosis. CLASSIFICATON OF EVIDENCE: This study provides Class III evidence that (18)F-FDG PET accurately distinguishes patients with ALS from normal controls (sensitivity 95.4%, specificity 82.5%). PMID- 25122208 TI - A transposable element insertion confers xenobiotic resistance in Drosophila. AB - The increase in availability of whole genome sequences makes it possible to search for evidence of adaptation at an unprecedented scale. Despite recent progress, our understanding of the adaptive process is still very limited due to the difficulties in linking adaptive mutations to their phenotypic effects. In this study, we integrated different levels of biological information to pinpoint the ecologically relevant fitness effects and the underlying molecular and biochemical mechanisms of a putatively adaptive TE insertion in Drosophila melanogaster: the pogo transposon FBti0019627. We showed that other than being incorporated into Kmn1 transcript, FBti0019627 insertion also affects the polyadenylation signal choice of CG11699 gene. Consequently, only the short 3'UTR transcript of CG11699 gene is produced and the expression level of this gene is higher in flies with the insertion. Our results indicated that increased CG11699 expression leads to xenobiotic stress resistance through increased ALDH-III activity: flies with FBti0019627 insertion showed increased survival rate in response to benzaldehyde, a natural xenobiotic, and to carbofuran, a synthetic insecticide. Although differences in survival rate between flies with and without the insertion were not always significant, when they were, they were consistent with FBti0019627 mediating resistance to xenobiotics. Taken together, our results provide a plausible explanation for the increase in frequency of FBti0019627 in natural populations of D. melanogaster and add to the limited number of examples in which a natural genetic mutation has been linked to its ecologically relevant phenotype. Furthermore, the widespread distribution of TEs across the tree of life and conservation of stress response pathways across organisms make our results relevant not only for Drosophila, but for other organisms as well. PMID- 25122209 TI - A scalable and accurate targeted gene assembly tool (SAT-Assembler) for next generation sequencing data. AB - Gene assembly, which recovers gene segments from short reads, is an important step in functional analysis of next-generation sequencing data. Lacking quality reference genomes, de novo assembly is commonly used for RNA-Seq data of non model organisms and metagenomic data. However, heterogeneous sequence coverage caused by heterogeneous expression or species abundance, similarity between isoforms or homologous genes, and large data size all pose challenges to de novo assembly. As a result, existing assembly tools tend to output fragmented contigs or chimeric contigs, or have high memory footprint. In this work, we introduce a targeted gene assembly program SAT-Assembler, which aims to recover gene families of particular interest to biologists. It addresses the above challenges by conducting family-specific homology search, homology-guided overlap graph construction, and careful graph traversal. It can be applied to both RNA-Seq and metagenomic data. Our experimental results on an Arabidopsis RNA-Seq data set and two metagenomic data sets show that SAT-Assembler has smaller memory usage, comparable or better gene coverage, and lower chimera rate for assembling a set of genes from one or multiple pathways compared with other assembly tools. Moreover, the family-specific design and rapid homology search allow SAT Assembler to be naturally compatible with parallel computing platforms. The source code of SAT-Assembler is available at https://sourceforge.net/projects/sat assembler/. The data sets and experimental settings can be found in supplementary material. PMID- 25122210 TI - IL-31 associated with coronary artery lesion formation in Kawasaki disease. AB - BACKGROUND: Kawasaki disease (KD) is known to be associated with T help (Th) 2 reaction and subsequently allergic diseases. Interleukin-31 (IL-31) has also been reported to be involved in Th2 mediated diseases such as allergic diseases. However, the role of IL-31 in KD has not been previously reported. The aim of this study is to investigate whether IL-31 is associated with KD and its clinical outcome. MATERIAL: A total of 78 KD patients who met the criteria of KD were enrolled in this study as well as 20 age-matched controls. Plasma samples were conducted to measure IL-31 before intravenous immunoglobulin (IVIG) treatment (KD1), within 3 days after IVIG treatment (KD2) and at least 3 weeks after IVIG treatment (KD3) by utilizing enzyme-linked immunosorbent assay (ELISA). RESULT: Our findings showed that IL-31 expression was higher in KD patients after IVIG treatment significantly (KD2>KD1: 1265.0+/-199.3 vs. 840.2+/-152.5 pg/ml, p<0.0001). Further analysis revealed that IL-31 level was significantly higher in KD patients with coronary artery lesion (CAL) (656.6+/-139.5 vs. 1373.0+/-422.0 pg/ml, p = 0.04) before IVIG treatment (KD1). There were no significant differences between the IVIG resistance and IVIG responsiveness groups. CONCLUSION: IL-31 was increased after IVIG treatment in patients with KD and was significantly associated with CAL formation. The results from this study may help to identify a novel risk factor for predicting KD and CAL formation. PMID- 25122211 TI - In-cell intrabody selection from a diverse human library identifies C12orf4 protein as a new player in rodent mast cell degranulation. AB - The high specificity of antibodies for their antigen allows a fine discrimination of target conformations and post-translational modifications, making antibodies the first choice tool to interrogate the proteome. We describe here an approach based on a large-scale intracellular expression and selection of antibody fragments in eukaryotic cells, so-called intrabodies, and the subsequent identification of their natural target within living cell. Starting from a phenotypic trait, this integrated system allows the identification of new therapeutic targets together with their companion inhibitory intrabody. We applied this system in a model of allergy and inflammation. We first cloned a large and highly diverse intrabody library both in a plasmid and a retroviral eukaryotic expression vector. After transfection in the RBL-2H3 rat basophilic leukemia cell line, we performed seven rounds of selection to isolate cells displaying a defect in FcepsilonRI-induced degranulation. We used high throughput sequencing to identify intrabody sequences enriched during the course of selection. Only one intrabody was common to both plasmid and retroviral selections, and was used to capture and identify its target from cell extracts. Mass spectrometry analysis identified protein RGD1311164 (C12orf4), with no previously described function. Our data demonstrate that RGD1311164 is a cytoplasmic protein implicated in the early signaling events following FcepsilonRI-induced cell activation. This work illustrates the strength of the intrabody-based in-cell selection, which allowed the identification of a new player in mast cell activation together with its specific inhibitor intrabody. PMID- 25122214 TI - Evidence for two types of lateral interactions in visual perception of temporal signals. AB - The aim of this work was to investigate the mechanisms of lateral interactions involved in flicker perception. Furthermore, the spatial properties of the monoptic and dichoptic components of these mechanisms were studied. We quantified the perceived flicker strength (PFS) in the center of a test stimulus, which was simultaneously modulated with a surround stimulus of variable size. The modulation depth of a separate stimulus, identical to the center test stimulus but without the surround, was determined using a two-alternative forced choice procedure. Using LCD goggles synchronized to the frame rate of a CRT screen, the center and surround of the test stimulus were presented either monoptically or dichoptically. In the monoptic condition, center-surround interactions have subcortical and cortical origins. In the dichoptic condition, center-surround interactions must have a cortical origin. The difference between the dichoptic and the monoptic data is an estimate of the contribution of the subcortical mechanisms. At each condition (surround stimulus size; monoptic or dichoptic presentation), the PFS was measured for phase differences between center and surround stimuli. The PFS changed systematically with phase difference. It also was observed that the PFS in the center stimulus changed merely be the presence of a surround stimulus independently of the center-surround phase difference. We propose that this is a phase-independent mechanism related to contrast adaptation owing to the presence of surround modulation. Our data suggest that both phase dependent and -independent mechanisms have cortical and subcortical origins. There were no systematic differences between the spatial properties of subcortical and cortical components involved in PFS modulation. PMID- 25122213 TI - Scaling-up access to antiretroviral therapy for children: a cohort study evaluating care and treatment at mobile and hospital-affiliated HIV clinics in rural Zambia. AB - BACKGROUND: Travel time and distance are barriers to care for HIV-infected children in rural sub-Saharan Africa. Decentralization of care is one strategy to scale-up access to antiretroviral therapy (ART), but few programs have been evaluated. We compared outcomes for children receiving care in mobile and hospital-affiliated HIV clinics in rural Zambia. METHODS: Outcomes were measured within an ongoing cohort study of HIV-infected children seeking care at Macha Hospital, Zambia from 2007 to 2012. Children in the outreach clinic group received care from the Macha HIV clinic and transferred to one of three outreach clinics. Children in the hospital-affiliated clinic group received care at Macha HIV clinic and reported Macha Hospital as the nearest healthcare facility. RESULTS: Seventy-seven children transferred to the outreach clinics and were included in the analysis. Travel time to the outreach clinics was significantly shorter and fewer caretakers used public transportation, resulting in lower transportation costs and fewer obstacles accessing the clinic. Some caretakers and health care providers reported inferior quality of service provision at the outreach clinics. Sixty-eight children received ART at the outreach clinics and were compared to 41 children in the hospital-affiliated clinic group. At ART initiation, median age, weight-for-age z-scores (WAZ) and CD4(+) T-cell percentages were similar for children in the hospital-affiliated and outreach clinic groups. Children in both groups experienced similar increases in WAZ and CD4(+) T-cell percentages. CONCLUSIONS: HIV care and treatment can be effectively delivered to HIV-infected children at rural health centers through mobile ART teams, removing potential barriers to uptake and retention. Outreach teams should be supported to increase access to HIV care and treatment in rural areas. PMID- 25122212 TI - The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. AB - A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ binding motif (PBM), a domain involved in protein-protein interactions, is a major determinant of virulence. Elimination of SARS-CoV E protein PBM by using reverse genetics caused a reduction in the deleterious exacerbation of the immune response triggered during infection with the parental virus and virus attenuation. Cellular protein syntenin was identified to bind the E protein PBM during SARS-CoV infection by using three complementary strategies, yeast two hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin redistributed from the nucleus to the cell cytoplasm during infection with viruses containing the E protein PBM, activating p38 MAPK and leading to the overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led to a decrease in p38 MAPK activation in SARS-CoV infected cells, further reinforcing their functional relationship. Active p38 MAPK was reduced in lungs of mice infected with SARS-CoVs lacking E protein PBM as compared with the parental virus, leading to a decreased expression of inflammatory cytokines and to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led to an increase in mice survival after infection with SARS-CoV, confirming the relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is a virulence domain that activates immunopathology most likely by using syntenin as a mediator of p38 MAPK induced inflammation. PMID- 25122215 TI - Encoding of configural regularity in the human visual system. AB - The visual system is very efficient in encoding stimulus properties by utilizing available regularities in the inputs. To explore the underlying encoding strategies during visual information processing, we presented participants with two-line configurations that varied in the amount of configural regularity (or degrees of freedom in the relative positioning of the two lines) in a fMRI experiment. Configural regularity ranged from a generic configuration to stimuli resembling an "L" (i.e., a right-angle L-junction), a "T" (i.e., a right-angle midpoint T-junction), or a "+",-the latter being the most regular stimulus. We found that the response strength in the shape-selective lateral occipital area was consistently lower for a higher degree of regularity in the stimuli. In the second experiment, using multivoxel pattern analysis, we further show that regularity is encoded in terms of the fMRI signal strength but not in the distributed pattern of responses. Finally, we found that the results of these experiments could not be accounted for by low-level stimulus properties and are distinct from norm-based encoding. Our results suggest that regularity plays an important role in stimulus encoding in the ventral visual processing stream. PMID- 25122216 TI - Accuracy and speed of material categorization in real-world images. AB - It is easy to visually distinguish a ceramic knife from one made of steel, a leather jacket from one made of denim, and a plush toy from one made of plastic. Most studies of material appearance have focused on the estimation of specific material properties such as albedo or surface gloss, and as a consequence, almost nothing is known about how we recognize material categories like leather or plastic. We have studied judgments of high-level material categories with a diverse set of real-world photographs, and we have shown (Sharan, 2009) that observers can categorize materials reliably and quickly. Performance on our tasks cannot be explained by simple differences in color, surface shape, or texture. Nor can the results be explained by observers merely performing shape-based object recognition. Rather, we argue that fast and accurate material categorization is a distinct, basic ability of the visual system. PMID- 25122217 TI - Exploring heterozygosity-survival correlations in a wild songbird population: contrasting effects between juvenile and adult stages. AB - The relationship between genetic diversity and fitness, a major issue in evolutionary and conservation biology, is expected to be stronger in traits affected by many loci and those directly influencing fitness. Here we explore the influence of heterozygosity measured at 15 neutral markers on individual survival, one of the most important parameters determining individual fitness. We followed individual survival up to recruitment and during subsequent adult life of 863 fledgling pied flycatchers born in two consecutive breeding seasons. Mark recapture analyses showed that individual heterozygosity did not influence juvenile or adult survival. In contrast, the genetic relatedness of parents was negatively associated with the offspring's survival during the adult life, but this effect was not apparent in the juvenile (from fledgling to recruitment) stage. Stochastic factors experienced during the first year of life in this long distance migratory species may have swamped a relationship between heterozygosity and survival up to recruitment. PMID- 25122218 TI - Improving children's oral health: an interdisciplinary research framework. AB - Despite the concerted efforts of research and professional and advocacy stakeholders, recent evidence suggests that improvements in the oral health of young children in the United States has not followed the prevailing trend of oral health improvement in other age groups. In fact, oral health disparities in the youngest children may be widening, yet efforts to translate advances in science and technology into meaningful improvements in populations' health have had limited success. Nevertheless, the great strides in genomics, biological, behavioral, social, and health services research in the past decade have strengthened the evidence base available to support initiatives and translational efforts. Concerted actions to accelerate this translation and implementation process are warranted; at the same time, policies that can help tackle the upstream determinants of oral health disparities are imperative. This article summarizes the proceedings from the symposium on the interdisciplinary continuum of pediatric oral health that was held during the 43rd annual meeting of the American Association for Dental Research, Charlotte, North Carolina, USA. This report showcases the latest contributions across the interdisciplinary continuum of pediatric oral health research and provides insights into future research priorities and necessary intersectoral synergies. Issues are discussed as related to the overwhelming dominance of social determinants on oral disease and the difficulty of translating science into action. PMID- 25122220 TI - Quantifying the role of population subdivision in evolution on rugged fitness landscapes. AB - Natural selection drives populations towards higher fitness, but crossing fitness valleys or plateaus may facilitate progress up a rugged fitness landscape involving epistasis. We investigate quantitatively the effect of subdividing an asexual population on the time it takes to cross a fitness valley or plateau. We focus on a generic and minimal model that includes only population subdivision into equivalent demes connected by global migration, and does not require significant size changes of the demes, environmental heterogeneity or specific geographic structure. We determine the optimal speedup of valley or plateau crossing that can be gained by subdivision, if the process is driven by the deme that crosses fastest. We show that isolated demes have to be in the sequential fixation regime for subdivision to significantly accelerate crossing. Using Markov chain theory, we obtain analytical expressions for the conditions under which optimal speedup is achieved: valley or plateau crossing by the subdivided population is then as fast as that of its fastest deme. We verify our analytical predictions through stochastic simulations. We demonstrate that subdivision can substantially accelerate the crossing of fitness valleys and plateaus in a wide range of parameters extending beyond the optimal window. We study the effect of varying the degree of subdivision of a population, and investigate the trade-off between the magnitude of the optimal speedup and the width of the parameter range over which it occurs. Our results, obtained for fitness valleys and plateaus, also hold for weakly beneficial intermediate mutations. Finally, we extend our work to the case of a population connected by migration to one or several smaller islands. Our results demonstrate that subdivision with migration alone can significantly accelerate the crossing of fitness valleys and plateaus, and shed light onto the quantitative conditions necessary for this to occur. PMID- 25122221 TI - Clonal expansion of the Pseudogymnoascus destructans genotype in North America is accompanied by significant variation in phenotypic expression. AB - Pseudogymnoascus destructans is the causative agent of an emerging infectious disease that threatens populations of several North American bat species. The fungal disease was first observed in 2006 and has since caused the death of nearly six million bats. The disease, commonly known as white-nose syndrome, is characterized by a cutaneous infection with P. destructans causing erosions and ulcers in the skin of nose, ears and/or wings of bats. Previous studies based on sequences from eight loci have found that isolates of P. destructans from bats in the US all belong to one multilocus genotype. Using the same multilocus sequence typing method, we found that isolates from eastern and central Canada also had the same genotype as those from the US, consistent with the clonal expansion of P. destructans into Canada. However, our PCR fingerprinting revealed that among the 112 North American isolates we analyzed, three, all from Canada, showed minor genetic variation. Furthermore, we found significant variations among isolates in mycelial growth rate; the production of mycelial exudates; and pigment production and diffusion into agar media. These phenotypic differences were influenced by culture medium and incubation temperature, indicating significant variation in environmental condition--dependent phenotypic expression among isolates of the clonal P. destructans genotype in North America. PMID- 25122222 TI - Long-term sonographic and serological follow-up of inactive echinococcal cysts of the liver: hints for a "watch-and-wait" approach. AB - Human cystic echinococcosis is a chronic, complex and neglected infection. Its clinical management has evolved over decades without adequate evaluation of efficacy. Recent expert opinion recommends that uncomplicated inactive cysts of the liver should be left untreated and solely monitored over time ("watch-and wait" approach). However, clinical data supporting this approach are still scant and published mostly as conference proceedings. In this study, we report our experience with long-term sonographic and serological follow-up of inactive cysts of the liver. From March 1994 to October 2013, 38 patients with 47 liver cysts, diagnosed as inactive without any previous treatment history, were followed with ultrasound and serology at 6-12 months intervals for a period of at least 24 months (median follow-up 51.95 months) in our outpatient clinic. In 97.4% of patients, the cysts remained inactive over time and in only one case was reactivation of the cyst detected. No complications occurred during the time of monitoring. During follow-up, serology tests for CE were negative at diagnosis or became negative in 74.1% and were positive or became positive in 25.9% of cases. Patients with inactive cysts on ultrasound but positive serological tests were also investigated by CT scan (chest and abdomen) to rule out extra-hepatic cyst localization. This study confirms the importance of a stage-specific approach to the management of cystic echinococcosis and supports the use of a monitoring-only approach to inactive, uncomplicated cysts of the liver. It also confirms that serology plays only an ancillary role in the clinical management of these patients, compared to ultrasound and other imaging techniques. The implications of these findings for clinical management and natural history of cystic echinococcosis are discussed. PMID- 25122219 TI - Histone deacetylase inhibitors impair the elimination of HIV-infected cells by cytotoxic T-lymphocytes. AB - Resting memory CD4+ T-cells harboring latent HIV proviruses represent a critical barrier to viral eradication. Histone deacetylase inhibitors (HDACis), such as suberanilohydroxamic acid (SAHA), romidepsin, and panobinostat have been shown to induce HIV expression in these resting cells. Recently, it has been demonstrated that the low levels of viral gene expression induced by a candidate HDACi may be insufficient to cause the death of infected cells by viral cytopathic effects, necessitating their elimination by immune effectors, such as cytotoxic T lymphocytes (CTL). Here, we study the impact of three HDACis in clinical development on T-cell effector functions. We report two modes of HDACi-induced functional impairment: i) the rapid suppression of cytokine production from viable T-cells induced by all three HDACis ii) the selective death of activated T cells occurring at later time-points following transient exposures to romidepsin or, to a lesser extent, panobinostat. As a net result of these factors, HDACis impaired CTL-mediated IFN-gamma production, as well as the elimination of HIV infected or peptide-pulsed target cells, both in liquid culture and in collagen matrices. Romidepsin exerted greater inhibition of antiviral function than SAHA or panobinostat over the dose ranges tested. These data suggest that treatment with HDACis to mobilize the latent reservoir could have unintended negative impacts on the effector functions of CTL. This could influence the effectiveness of HDACi-based eradication strategies, by impairing elimination of infected cells, and is a critical consideration for trials where therapeutic interruptions are being contemplated, given the importance of CTL in containing rebound viremia. PMID- 25122223 TI - Temporally dynamic habitat suitability predicts genetic relatedness among caribou. AB - Landscape heterogeneity plays a central role in shaping ecological and evolutionary processes. While species utilization of the landscape is usually viewed as constant within a year, the spatial distribution of individuals is likely to vary in time in relation to particular seasonal needs. Understanding temporal variation in landscape use and genetic connectivity has direct conservation implications. Here, we modelled the daily use of the landscape by caribou in Quebec and Labrador, Canada and tested its ability to explain the genetic relatedness among individuals. We assessed habitat selection using locations of collared individuals in migratory herds and static occurrences from sedentary groups. Connectivity models based on habitat use outperformed a baseline isolation-by-distance model in explaining genetic relatedness, suggesting that variations in landscape features such as snow, vegetation productivity and land use modulate connectivity among populations. Connectivity surfaces derived from habitat use were the best predictors of genetic relatedness. The relationship between connectivity surface and genetic relatedness varied in time and peaked during the rutting period. Landscape permeability in the period of mate searching is especially important to allow gene flow among populations. Our study highlights the importance of considering temporal variations in habitat selection for optimizing connectivity across heterogeneous landscape and counter habitat fragmentation. PMID- 25122224 TI - Hox gene duplications correlate with posterior heteronomy in scorpions. AB - The evolutionary success of the largest animal phylum, Arthropoda, has been attributed to tagmatization, the coordinated evolution of adjacent metameres to form morphologically and functionally distinct segmental regions called tagmata. Specification of regional identity is regulated by the Hox genes, of which 10 are inferred to be present in the ancestor of arthropods. With six different posterior segmental identities divided into two tagmata, the bauplan of scorpions is the most heteronomous within Chelicerata. Expression domains of the anterior eight Hox genes are conserved in previously surveyed chelicerates, but it is unknown how Hox genes regionalize the three tagmata of scorpions. Here, we show that the scorpion Centruroides sculpturatus has two paralogues of all Hox genes except Hox3, suggesting cluster and/or whole genome duplication in this arachnid order. Embryonic anterior expression domain boundaries of each of the last four pairs of Hox genes (two paralogues each of Antp, Ubx, abd-A and Abd-B) are unique and distinguish segmental groups, such as pectines, book lungs and the characteristic tail, while maintaining spatial collinearity. These distinct expression domains suggest neofunctionalization of Hox gene paralogues subsequent to duplication. Our data reconcile previous understanding of Hox gene function across arthropods with the extreme heteronomy of scorpions. PMID- 25122225 TI - Maternal exposure to predator scents: offspring phenotypic adjustment and dispersal. AB - Predation is a strong selective pressure generating morphological, physiological and behavioural responses in organisms. As predation risk is often higher during juvenile stages, antipredator defences expressed early in life are paramount to survival. Maternal effects are an efficient pathway to produce such defences. We investigated whether maternal exposure to predator cues during gestation affected juvenile morphology, behaviour and dispersal in common lizards (Zootoca vivipara). We exposed 21 gravid females to saurophagous snake cues for one month while 21 females remained unexposed (i.e. control). We measured body size, preferred temperature and activity level for each neonate, and released them into semi-natural enclosures connected to corridors in order to measure dispersal. Offspring from exposed mothers grew longer tails, selected lower temperatures and dispersed thrice more than offspring from unexposed mothers. Because both tail autotomy and altered thermoregulatory behaviour are common antipredator tactics in lizards, these results suggest that mothers adjusted offspring phenotype to risky natal environments (tail length) or increased risk avoidance (dispersal). Although maternal effects can be passive consequences of maternal stress, our results strongly militate for them to be an adaptive antipredator response that may increase offspring survival prospects. PMID- 25122226 TI - Early life expenditure in sexual competition is associated with increased reproductive senescence in male red deer. AB - The evolutionary theories of senescence predict that investment in reproduction in early life should come at the cost of reduced somatic maintenance, and thus earlier or more rapid senescence. There is now growing support for such trade offs in wild vertebrates, but these exclusively come from females. Here, we test this prediction in male red deer (Cervus elaphus) using detailed longitudinal data collected over a 40-year field study. We show that males which had larger harems and thereby allocated more resources to reproduction during early adulthood experienced higher rates of senescence in both harem size and rut duration. Males that carried antlers with more points during early life did not show more pronounced declines in reproductive traits in later life. Overall, we demonstrate that sexual competition shapes male reproductive senescence in wild red deer populations and provide rare empirical support for the disposable soma theory of ageing in males of polygynous vertebrate species. PMID- 25122227 TI - Cryptic cuckoo eggs hide from competing cuckoos. AB - Interspecific arms races between cuckoos and their hosts have produced remarkable examples of mimicry, with parasite eggs evolving to match host egg appearance and so evade removal by hosts. Certain bronze-cuckoo species, however, lay eggs that are cryptic rather than mimetic. These eggs are coated in a low luminance pigment that camouflages them within the dark interiors of hosts' nests. We investigated whether cuckoo egg crypsis is likely to have arisen from the same coevolutionary processes known to favour egg mimicry. We added high and low luminance-painted eggs to the nests of large-billed gerygones (Gerygone magnirostris), a host of the little bronze-cuckoo (Chalcites minutillus). Gerygones rarely rejected either egg type, and did not reject natural cuckoo eggs. Cuckoos, by contrast, regularly removed an egg from clutches before laying their own and were five times more likely to remove a high luminance model than its low luminance counterpart. Given that we found one-third of all parasitized nests were exploited by multiple cuckoos, our results suggest that competition between cuckoos has been the key selective agent for egg crypsis. In such intraspecific arms races, crypsis may be favoured over mimicry because it can reduce the risk of egg removal to levels below chance. PMID- 25122229 TI - Contrasting effects of large density changes on relative testes size in fluctuating populations of sympatric vole species. AB - Across species, there is usually a positive relationship between sperm competition level and male reproductive effort on ejaculates, typically measured using relative testes size (RTS). Within populations, demographic and ecological processes may drastically alter the level of sperm competition and thus, potentially affect the evolution of testes size. Here, we use longitudinal records (across 38 years) from wild sympatric Fennoscandian populations of five species of voles to investigate whether RTS responds to natural fluctuations in population density, i.e. variation in sperm competition risk. We show that for some species RTS increases with density. However, our results also show that this relationship can be reversed in populations with large-scale between-year differences in density. Multiple mechanisms are suggested to explain the negative RTS-density relationship, including testes size response to density-dependent species interactions, an evolutionary response to sperm competition levels that is lagged when density fluctuations are over a certain threshold, or differing investment in pre- and post-copulatory competition at different densities. The results emphasize that our understanding of sperm competition in fluctuating environments is still very limited. PMID- 25122228 TI - Three-way interactions between mosquito population, viral strain and temperature underlying chikungunya virus transmission potential. AB - Interactions between pathogens and their insect vectors in nature are under the control of both genetic and non-genetic factors, yet most studies on mosquito vector competence for human pathogens are conducted in laboratory systems that do not consider genetic and/or environmental variability. Evaluating the risk of emergence of arthropod-borne viruses (arboviruses) of public health importance such as chikungunya virus (CHIKV) requires a more realistic appraisal of genetic and environmental contributions to vector competence. In particular, sources of variation do not necessarily act independently and may combine in the form of interactions. Here, we measured CHIKV transmission potential by the mosquito Aedes albopictus in all combinations of six worldwide vector populations, two virus strains and two ambient temperatures (20 degrees C and 28 degrees C). Overall, CHIKV transmission potential by Ae. albopictus strongly depended on the three-way combination of mosquito population, virus strain and temperature. Such genotype-by-genotype-by-environment (G * G * E) interactions question the relevance of vector competence studies conducted with a simpler set of conditions. Our results highlight the need to account for the complex interplay between vectors, pathogens and environmental factors to accurately assess the potential of vector-borne diseases to emerge. PMID- 25122230 TI - Genetic elimination of field-cage populations of Mediterranean fruit flies. AB - The Mediterranean fruit fly (medfly, Ceratitis capitata Wiedemann) is a pest of over 300 fruits, vegetables and nuts. The sterile insect technique (SIT) is a control measure used to reduce the reproductive potential of populations through the mass release of sterilized male insects that mate with wild females. However, SIT flies can display poor field performance, due to the effects of mass-rearing and of the irradiation process used for sterilization. The development of female lethal RIDL (release of insects carrying a dominant lethal) strains for medfly can overcome many of the problems of SIT associated with irradiation. Here, we present life-history characterizations for two medfly RIDL strains, OX3864A and OX3647Q. Our results show (i) full functionality of RIDL, (ii) equivalency of RIDL and wild-type strains for life-history characteristics, and (iii) a high level of sexual competitiveness against both wild-type and wild-derived males. We also present the first proof-of-principle experiment on the use of RIDL to eliminate medfly populations. Weekly releases of OX3864A males into stable populations of wild-type medfly caused a successive decline in numbers, leading to eradication. The results show that genetic control can provide an effective alternative to SIT for the control of pest insects. PMID- 25122231 TI - Prediction of phylogeographic endemism in an environmentally complex biome. AB - Phylogeographic endemism, the degree to which the history of recently evolved lineages is spatially restricted, reflects fundamental evolutionary processes such as cryptic divergence, adaptation and biological responses to environmental heterogeneity. Attempts to explain the extraordinary diversity of the tropics, which often includes deep phylogeographic structure, frequently invoke interactions of climate variability across space, time and topography. To evaluate historical versus contemporary drivers of phylogeographic endemism in a tropical system, we analyse the effects of current and past climatic variation on the genetic diversity of 25 vertebrates in the Brazilian Atlantic rainforest. We identify two divergent bioclimatic domains within the forest and high turnover around the Rio Doce. Independent modelling of these domains demonstrates that endemism patterns are subject to different climatic drivers. Past climate dynamics, specifically areas of relative stability, predict phylogeographic endemism in the north. Conversely, contemporary climatic heterogeneity better explains endemism in the south. These results accord with recent speleothem and fossil pollen studies, suggesting that climatic variability through the last 250 kyr impacted the northern and the southern forests differently. Incorporating sub regional differences in climate dynamics will enhance our ability to understand those processes shaping high phylogeographic and species endemism, in the Neotropics and beyond. PMID- 25122232 TI - Facial fluctuating asymmetry is not associated with childhood ill-health in a large British cohort study. AB - The idea that symmetry in facial traits is associated with attractiveness because it reliably indicates good physiological health, particularly to potential sexual partners, has generated an extensive literature on the evolution of human mate choice. However, large-scale tests of this hypothesis using direct or longitudinal assessments of physiological health are lacking. Here, we investigate relationships between facial fluctuating asymmetry (FA) and detailed individual health histories in a sample (n = 4732) derived from a large longitudinal study (Avon Longitudinal Study of Parents and Children) in South West England. Facial FA was assessed using geometric morphometric analysis of facial landmark configurations derived from three-dimensional facial scans taken at 15 years of age. Facial FA was not associated with longitudinal measures of childhood health. However, there was a very small negative association between facial FA and IQ that remained significant after correcting for a positive allometric relationship between FA and face size. Overall, this study does not support the idea that facial symmetry acts as a reliable cue to physiological health. Consequently, if preferences for facial symmetry do represent an evolved adaptation, then they probably function not to provide marginal fitness benefits by choosing between relatively healthy individuals on the basis of small differences in FA, but rather evolved to motivate avoidance of markers of substantial developmental disturbance and significant pathology. PMID- 25122234 TI - Consistent inference of a general model using the pseudolikelihood method. AB - Recently, a maximum pseudolikelihood (MPL) inference method has been successfully applied to statistical physics models with intractable likelihoods. We use information theory to derive a relation between the pseudolikelihood and likelihood functions. Furthermore, we show the consistency of the pseudolikelihood method for a general model. PMID- 25122233 TI - Costs for switching partners reduce network dynamics but not cooperative behaviour. AB - Social networks represent the structuring of interactions between group members. Above all, many interactions are profoundly cooperative in humans and other animals. In accordance with this natural observation, theoretical work demonstrates that certain network structures favour the evolution of cooperation. Yet, recent experimental evidence suggests that static networks do not enhance cooperative behaviour in humans. By contrast, dynamic networks do foster cooperation. However, costs associated with dynamism such as time or resource investments in finding and establishing new partnerships have been neglected so far. Here, we show that human participants are much less likely to break links when costs arise for building new links. Especially, when costs were high, the network was nearly static. Surprisingly, cooperation levels in Prisoner's Dilemma games were not affected by reduced dynamism in social networks. We conclude that the mere potential to quit collaborations is sufficient in humans to reach high levels of cooperative behaviour. Effects of self-structuring processes or assortment on the network played a minor role: participants simply adjusted their cooperative behaviour in response to the threats of losing a partner or of being expelled. PMID- 25122235 TI - Particle diagrams and embedded many-body random matrix theory. AB - We present a method which uses Feynman-like diagrams to calculate the statistical quantities of embedded many-body random matrix problems. The method provides a promising alternative to existing techniques and offers many important simplifications. We use it here to find the fourth, sixth, and eighth moments of the level density of an m-body system with k fermions or bosons interacting through a random Hermitian potential (k <= m) in the limit where the number of possible single-particle states is taken to infinity. All share the same transition, starting immediately after 2k = m, from moments arising from a semicircular level density to Gaussian moments. The results also reveal a striking feature; the domain of the 2nth moment is naturally divided into n subdomains specified by the points 2k = m,3 k = m,...,nk = m. PMID- 25122236 TI - Anomalous preasymptotic colloid transport by hydrodynamic dispersion in microfluidic capillary flow. AB - The anomalous preasymptotic transport of colloids in a microfluidic capillary flow due to hydrodynamic dispersion is measured by noninvasive nuclear magnetic resonance (NMR). The data indicate a reduced scaling of mean squared displacement with time from the (c) ~ t(3) behavior for the interaction of a normal diffusion process with a simple shear flow. This nonequilibrium steady-state system is shown to be modeled by a continuous time random walk (CTRW) on a moving fluid. The full propagator of the motion is measured by NMR, providing verification of the assumption of Gaussian jump length distributions in the CTRW model. The connection of the data to microrheology measurements by NMR, in which every particle in a suspension contributes information, is established. PMID- 25122239 TI - Derivation of a neural field model from a network of theta neurons. AB - Neural field models are used to study macroscopic spatiotemporal patterns in the cortex. Their derivation from networks of model neurons normally involves a number of assumptions, which may not be correct. Here we present an exact derivation of a neural field model from an infinite network of theta neurons, the canonical form of a type I neuron. We demonstrate the existence of a "bump" solution in both a discrete network of neurons and in the corresponding neural field model. PMID- 25122237 TI - Effective attenuation length of an electron in liquid water between 10 and 600 eV. AB - The absolute values of the effective attenuation length of an electron in liquid water are determined using soft x-ray O1s photoemission spectroscopy of a liquid beam of water without employing any theoretical estimation or computationally obtained value. The effective attenuation length is greater than 1 nm in the entire electron kinetic energy region and exhibits very flat energy dependence in the 10-100 eV region. PMID- 25122238 TI - Order parameter for structural heterogeneity in disordered solids. AB - We construct a structural order parameter from the energy equipartition of normal modes of vibration to quantify the structural heterogeneity in disordered solids. The order parameter exhibits strong spatial correlations with low-temperature dynamics and local structural entropy. To characterize the role of particles with the most defective local structures identified by the order parameter, we pin them and measure the system response. It turns out that particles with the largest value of the order parameter are responsible for the quasilocalized low frequency vibration, instability, softening, and nonaffinity of disordered solids. The order parameter thus crucially links the heterogeneous structure to low-temperature dynamics and mechanical properties of disordered solids. PMID- 25122240 TI - Front propagation in cellular flows for fast reaction and small diffusivity. AB - We investigate the influence of fluid flows on the propagation of chemical fronts arising in Fisher-Kolmogorov-Petrovsky-Piskunov (FKPP) type models. We develop an asymptotic theory for the front speed in a cellular flow in the limit of small molecular diffusivity and fast reaction, i.e., large Peclet (Pe) and Damkohler (Da) numbers. The front speed is expressed in terms of a periodic path--an instanton--that minimizes a certain functional. This leads to an efficient procedure to calculate the front speed, and to closed-form expressions for (logPe)(-1) ? Da ? Pe and for Da ? Pe. Our theoretical predictions are compared with (i) numerical solutions of an eigenvalue problem and (ii) simulations of the advection-diffusion-reaction equation. PMID- 25122241 TI - Dynamics of strongly correlated and strongly inhomogeneous plasmas. AB - Kinetic and fluid equations are derived for the dynamics of classical inhomogeneous trapped plasmas in the strong coupling regime. The starting point is an extended Singwi-Tosi-Land-Sjolander (STLS) ansatz for the dynamic correlation function, which is allowed to depend on time and both particle coordinates separately. The time evolution of the correlation function is determined from the second equation of the Bogolyubov-Born-Green-Kirkwood-Yvon hierarchy. We study the equations in the linear limit and derive a nonlocal equation for the fluid displacement field. Comparisons to first-principles molecular dynamics simulations reveal an excellent quality of our approach thereby overcoming the limitations of the broadly used STLS scheme. PMID- 25122243 TI - Generalized Klein-Gordon models: behavior around the ground state condensate. AB - In this work, we investigate the balance between the nonlinear and linear interaction energy of an interparticle anharmonic system in the vicinity of the ground state condensate. As a result, we find that the nonlinear interaction energy is very significant in the vicinity of each degree of freedom. We address some potential applications of the findings to miscellaneous areas of interests such as soliton theory, hydrodynamics, solid state physics, ferromagnetic and ferroelectric domain walls, condensed matter physics, and particle physics, among others. PMID- 25122244 TI - Estimation of probability densities using scale-free field theories. AB - The question of how best to estimate a continuous probability density from finite data is an intriguing open problem at the interface of statistics and physics. Previous work has argued that this problem can be addressed in a natural way using methods from statistical field theory. Here I describe results that allow this field-theoretic approach to be rapidly and deterministically computed in low dimensions, making it practical for use in day-to-day data analysis. Importantly, this approach does not impose a privileged length scale for smoothness of the inferred probability density, but rather learns a natural length scale from the data due to the tradeoff between goodness of fit and an Occam factor. Open source software implementing this method in one and two dimensions is provided. PMID- 25122242 TI - Reduced instability growth with high-adiabat high-foot implosions at the National Ignition Facility. AB - Hydrodynamic instabilities are a major obstacle in the quest to achieve ignition as they cause preexisting capsule defects to grow and ultimately quench the fusion burn in experiments at the National Ignition Facility. Unstable growth at the ablation front has been dramatically reduced in implosions with "high-foot" drives as measured using x-ray radiography of modulations at the most dangerous wavelengths (Legendre mode numbers of 30-90). These growth reductions have helped to improve the performance of layered DT implosions reported by O. A. Hurricane et al. [Nature (London) 506, 343 (2014)], when compared to previous "low-foot" experiments, demonstrating the value of stabilizing ablation-front growth and providing directions for future ignition designs. PMID- 25122245 TI - Depinning of stiff directed lines in random media. AB - Driven elastic manifolds in random media exhibit a depinning transition to a state with nonvanishing velocity at a critical driving force. We study the depinning of stiff directed lines, which are governed by a bending rigidity rather than line tension. Their equation of motion is the (quenched) Herring Mullins equation, which also describes surface growth governed by surface diffusion. Stiff directed lines are particularly interesting as there is a localization transition in the static problem at a finite temperature and the commonly exploited time ordering of states by means of Middleton's theorems [Phys. Rev. Lett. 68, 670 (1992)] is not applicable. We employ analytical arguments and numerical simulations to determine the critical exponents and compare our findings with previous works and functional renormalization group results, which we extend to the different line elasticity. We see evidence for two distinct correlation length exponents. PMID- 25122246 TI - Fisher exponent from pseudo-epsilon expansion. AB - The critical exponent eta for three-dimensional systems with an n-vector order parameter is evaluated in the framework of the pseudo-epsilon expansion approach. The pseudo-epsilon expansion (tau series) for eta found up to the tau(7) term for n = 0, 1, 2, 3 and within the tau(6) order for general n is shown to have a structure that is rather favorable for getting numerical estimates. The use of Pade approximants and direct summation of the tau series result in iteration procedures rapidly converging to the asymptotic values that are very close to the most reliable numerical estimates of eta known today. The origin of such an efficiency is discussed and shown to lie in the general properties of the pseudo epsilon expansion machinery interfering with some peculiarities of the renormalization group expansion of eta. PMID- 25122247 TI - Anomalous diffusion induced by enhancement of memory. AB - We introduced simple microscopic non-Markovian walk models which describe the underlying mechanism of anomalous diffusions. In the models, we considered the competitions between randomness and memory effects of previous history by introducing the probability parameters. The memory effects were considered in two aspects: one is the perfect memory of whole history and the other is the latest memory enhanced with time. In the perfect memory model superdiffusion was induced with the relation of the Hurst exponent H to the controlling parameter p as H = p for p>1/2, while in the latest memory enhancement models, anomalous diffusions involving both superdiffusion and subdiffusion were induced with the relations H = (1+alpha)/2 and H = (1-alpha)/2 for 0 <= alpha <= 1, where alpha is the parameter controlling the degree of the latest memory enhancement. Also we found that, although the latest memory was only considered, the memory improved with time results in the long-range correlations between steps and the correlations increase as time goes on. Thus we suggest the memory enhancement as a key origin describing anomalous diffusions. PMID- 25122249 TI - Topological phase transition in a discrete quasicrystal. AB - We investigate a two-dimensional tiling model. Even though the degrees of freedom in this model are discrete, it has a hidden continuous global symmetry in the infinite lattice limit, whose corresponding Goldstone modes are the quasicrystalline phasonic degrees of freedom. We show that due to this continuous symmetry and despite the apparent discrete nature of the model, a topological phase transition from a quasi-long-range ordered to a disordered phase occurs at a finite temperature, driven by vortex proliferation. We argue that some of the results are universal properties of two-dimensional systems whose ground state is a quasicrystalline state. PMID- 25122248 TI - Nonsteady dynamic properties of a domain wall for the creep state under an alternating driving field. AB - With Monte Carlo simulations, the nonsteady dynamic properties of a domain wall have been systematically investigated for the thermally activated creep state under an alternating driving field. Taking the driven random-field Ising model in two dimensions as an example, two distinct growth stages of the domain interface are identified with both the correlation length and roughness function. One stage belongs to the universality class of the random depositions, and the other to that of the quenched Edwards-Wilkinson equation. In the latter case, due to the dynamic effect of overhangs, the domain interface may exhibit an intrinsic anomalous scaling behavior, different from that of the quenched Edwards-Wilkinson equation. PMID- 25122250 TI - Thermodynamic properties and entropy scaling law for diffusivity in soft spheres. AB - The purely repulsive soft-sphere system, where the interaction potential is inversely proportional to the pair separation raised to the power n, is considered. The Laplace transform technique is used to derive its thermodynamic properties in terms of the potential energy and its density derivative obtained from molecular dynamics simulations. The derived expressions provide an analytic framework with which to explore soft-sphere thermodynamics across the whole softness-density fluid domain. The trends in the isochoric and isobaric heat capacity, thermal expansion coefficient, isothermal and adiabatic bulk moduli, Gruneisen parameter, isothermal pressure, and the Joule-Thomson coefficient as a function of fluid density and potential softness are described using these formulas supplemented by the simulation-derived equation of state. At low densities a minimum in the isobaric heat capacity with density is found, which is a new feature for a purely repulsive pair interaction. The hard-sphere and n = 3 limits are obtained, and the low density limit specified analytically for any n is discussed. The softness dependence of calculated quantities indicates freezing criteria based on features of the radial distribution function or derived functions of it are not expected to be universal. A new and accurate formula linking the self-diffusion coefficient to the excess entropy for the entire fluid softness-density domain is proposed, which incorporates the kinetic theory solution for the low density limit and an entropy-dependent function in an exponential form. The thermodynamic properties (or their derivatives), structural quantities, and diffusion coefficient indicate that three regions specified by a convex, concave, and intermediate density dependence can be expected as a function of n, with a narrow transition region within the range 5 < n < 8. PMID- 25122251 TI - Nonequilibrium ensemble inequivalence and large deviations of the density in the ABC model. AB - We consider the one-dimensional driven ABC model under particle-conserving and particle-nonconserving processes. Two limiting cases are studied: (a) The rates of the nonconserving processes are vanishingly slow compared with the conserving processes in the thermodynamic limit and (b) the two rates are comparable. For case (a) we provide a detailed analysis of the phase diagram and the large deviations function of the overall density, G(r). The phase diagram of the nonconserving model, derived from G(r), is found to be different from the conserving one. This difference, which stems from the nonconvexity of G(r), is analogous to ensemble inequivalence found in equilibrium systems with long-range interactions. An outline of the analysis of case (a) was given in an earlier letter. For case (b) we show that, unlike the conserving model, the nonconserving model exhibits a moving density profile in the steady state with a velocity that remains finite in the thermodynamic limit. Moreover, in contrast with case (a), the critical lines of the conserving and nonconserving models do not coincide. These are new features which are present only when the rates of the conserving and nonconserving processes are comparable. In addition, we analyze G(r) in case (b) using macroscopic fluctuations theory. Much of the derivation presented in this paper is applicable to any driven-diffusive system coupled to an external particle bath via a slow dynamics. PMID- 25122253 TI - Long-range correlations in a locally driven exclusion process. AB - We show that the presence of a driven bond in an otherwise diffusive lattice gas with simple exclusion interaction results in long-range density-density correlation in its stationary state. In dimensions d > 1 we show that in the thermodynamic limit this correlation decays as C(r,s)~(r(2)+s(2))(-d) at large distances r and s away from the drive with |r - s| ? 1. This is derived using an electrostatic analogy whereby C(r,s) is expressed as the potential due to a configuration of electrostatic charges distributed in 2d dimension. At bulk density rho=1/2 we show that the potential is that of a localized quadrupolar charge. At other densities the same is correct in leading order in the strength of the drive and it is argued numerically to be valid at higher orders. PMID- 25122252 TI - Generation of a tunable environment for electrical oscillator systems. AB - Many physical, chemical, and biological systems can be modeled by means of random frequency harmonic oscillator systems. Even though the noise-free evolution of harmonic oscillator systems can be easily implemented, the way to experimentally introduce, and control, noise effects due to a surrounding environment remains a subject of lively interest. Here, we experimentally demonstrate a setup that provides a unique tool to generate a fully tunable environment for classical electrical oscillator systems. We illustrate the operation of the setup by implementing the case of a damped random-frequency harmonic oscillator. The high degree of tunability and control of our scheme is demonstrated by gradually modifying the statistics of the oscillator's frequency fluctuations. This tunable system can readily be used to experimentally study interesting noise effects, such as noise-induced transitions in systems driven by multiplicative noise, and noise-induced transport, a phenomenon that takes place in quantum and classical coupled oscillator networks. PMID- 25122254 TI - Equilibrium states of generic quantum systems subject to periodic driving. AB - When a closed quantum system is driven periodically with period T, it approaches a periodic state synchronized with the drive in which any local observable measured stroboscopically approaches a steady value. For integrable systems, the resulting behavior is captured by a periodic version of a generalized Gibbs ensemble. By contrast, here we show that for generic nonintegrable interacting systems, local observables become independent of the initial state entirely. Essentially, this happens because Floquet eigenstates of the driven system at quasienergy omega(alpha) consist of a mixture of the exponentially many eigenstates of the undriven Hamiltonian, which are thus drawn from the entire extensive undriven spectrum. This is a form of equilibration which depends only on the Hilbert space of the undriven system and not on any details of its Hamiltonian. PMID- 25122255 TI - Self-propelled particle in an external potential: existence of an effective temperature. AB - We study a stationary state of a single self-propelled, athermal particle in linear and quadratic external potentials. The self-propulsion is modeled as a fluctuating internal driving force evolving according to the Ornstein-Uhlenbeck process, independently of the state of the particle. Without an external potential, in the long time limit, the self-propelled particle moving in a viscous medium performs diffusive motion, which allows one to identify an effective temperature. We show that in the presence of a linear external potential the stationary state distribution has an exponential form with the sedimentation length determined by the effective temperature of the free self propelled particle. In the presence of a quadratic external potential the stationary state distribution has a Gaussian form. However, in general, this distribution is not determined by the effective temperature of the free self propelled particle. PMID- 25122256 TI - Small-cluster renormalization group in Ising and Blume-Emery-Griffiths models with ferromagnetic, antiferromagnetic, and quenched disordered magnetic interactions. AB - The Ising and Blume-Emery-Griffiths (BEG) models' critical behavior is analyzed in two dimensions and three dimensions by means of a renormalization group scheme on small clusters made of a few lattice cells. Different kinds of cells are proposed for both ordered and disordered model cases. In particular, cells preserving a possible antiferromagnetic ordering under renormalization allow for the determination of the Neel critical point and its scaling indices. These also provide more reliable estimates of the Curie fixed point than those obtained using cells preserving only the ferromagnetic ordering. In all studied dimensions, the present procedure does not yield a strong-disorder critical point corresponding to the transition to the spin-glass phase. This limitation is thoroughly analyzed and motivated. PMID- 25122257 TI - Revisiting Feynman's ratchet with thermoelectric transport theory. AB - We show how the formalism used for thermoelectric transport may be adapted to Smoluchowski's seminal thought experiment, also known as Feynman's ratchet and pawl system. Our analysis rests on the notion of useful flux, which for a thermoelectric system is the electrical current and for Feynman's ratchet is the effective jump frequency. Our approach yields original insight into the derivation and analysis of the system's properties. In particular we define an entropy per tooth in analogy with the entropy per carrier or Seebeck coefficient, and we derive the analog to Kelvin's second relation for Feynman's ratchet. Owing to the formal similarity between the heat fluxes balance equations for a thermoelectric generator (TEG) and those for Feynman's ratchet, we introduce a distribution parameter gamma that quantifies the amount of heat that flows through the cold and hot sides of both heat engines. While it is well established that gamma = 1/2 for a TEG, it is equal to 1 for Feynman's ratchet. This implies that no heat may be rejected in the cold reservoir for the latter case. Further, the analysis of the efficiency at maximum power shows that the so-called Feynman efficiency corresponds to that of an exoreversible engine, with gamma = 1. Then, turning to the nonlinear regime, we generalize the approach based on the convection picture and introduce two different types of resistance to distinguish the dynamical behavior of the considered system from its ability to dissipate energy. We finally put forth the strong similarity between the original Feynman ratchet and a mesoscopic thermoelectric generator with a single conducting channel. PMID- 25122258 TI - Effect of coupling strength on a two-lane partially asymmetric coupled totally asymmetric simple exclusion process with Langmuir kinetics. AB - We analyze an open system comprised of two parallel totally asymmetric simple exclusion processes with particle attachment and detachment in the bulk under partially asymmetric coupling conditions. The phase diagrams are obtained using boundary layer analysis of continuum mean-field equations and characterized for different values of lane-changing rates. The structure of the phase diagram remains qualitatively the same as the one in fully asymmetric coupling conditions up to a certain critical order of lane-changing rates, after which significant changes are found in the phase diagram. The effect of system size on the steady state dynamics has also been examined. To validate theoretical findings, extensive Monte Carlo simulations are carried out. PMID- 25122259 TI - Energy pumping in electrical circuits under avalanche noise. AB - We theoretically study energy pumping processes in an electrical circuit with avalanche diodes, where non-Gaussian athermal noise plays a crucial role. We show that a positive amount of energy (work) can be extracted by an external manipulation of the circuit in a cyclic way, even when the system is spatially symmetric. We discuss the properties of the energy pumping process for both quasistatic and finite-time cases, and analytically obtain formulas for the amounts of the work and the power. Our results demonstrate the significance of the non-Gaussianity in energetics of electrical circuits. PMID- 25122260 TI - Role of the interpretation of stochastic calculus in systems with cross correlated Gaussian white noises. AB - We derive the Fokker-Planck equation for multivariable Langevin equations with cross-correlated Gaussian white noises for an arbitrary interpretation of the stochastic differential equation. We formulate the conditions when the solution of the Fokker-Planck equation does not depend on which stochastic calculus is adopted. Further, we derive an equivalent multivariable Ito stochastic differential equation for each possible interpretation of the multivariable Langevin equation. To demonstrate the usefulness and significance of these general results, we consider the motion of Brownian particles. We study in detail the stability conditions for harmonic oscillators with two white noises, one of which is additive, random forcing, and the other, which accounts for fluctuations of either the damping or the spring coefficient, is multiplicative. We analyze the role of cross correlation in terms of the different noise interpretations and confirm the theoretical predictions via numerical simulations. We stress the interest of our results for numerical simulations of stochastic differential equations with an arbitrary interpretation of the stochastic integrals. PMID- 25122261 TI - Scaling of clusters near discontinuous percolation transitions in hyperbolic networks. AB - We investigate the onset of the discontinuous percolation transition in small world hyperbolic networks by studying the systems-size scaling of the typical largest cluster approaching the transition, p ? p(c). To this end, we determine the average size of the largest cluster ~ N(Psi(p)) in the thermodynamic limit using real-space renormalization of cluster-generating functions for bond and site percolation in several models of hyperbolic networks that provide exact results. We determine that all our models conform to the recently predicted behavior regarding the growth of the largest cluster, which found diverging, albeit subextensive, clusters spanning the system with finite probability well below p(c) and at most quadratic corrections to unity in Psi(p) for p ? p(c). Our study suggests a large universality in the cluster formation on small-world hyperbolic networks and the potential for an alternative mechanism in the cluster formation dynamics at the onset of discontinuous percolation transitions. PMID- 25122262 TI - Scaling hypothesis for the Euclidean bipartite matching problem. AB - We propose a simple yet very predictive form, based on a Poisson's equation, for the functional dependence of the cost from the density of points in the Euclidean bipartite matching problem. This leads, for quadratic costs, to the analytic prediction of the large N limit of the average cost in dimension d = 1,2 and of the subleading correction in higher dimension. A nontrivial scaling exponent, gamma(d) = d-2/d, which differs from the monopartite's one, is found for the subleading correction. We argue that the same scaling holds true for a generic cost exponent in dimension d > 2. PMID- 25122263 TI - Optimal efficiency of a noisy quantum heat engine. AB - In this article we use optimal control to maximize the efficiency of a quantum heat engine executing the Otto cycle in the presence of external noise. We optimize the engine performance for both amplitude and phase noise. In the case of phase damping we additionally show that the ideal performance of a noiseless engine can be retrieved in the adiabatic (long time) limit. The results obtained here are useful in the quest for absolute zero, the design of quantum refrigerators that can cool a physical system to the lowest possible temperature. They can also be applied to the optimal control of a collection of classical harmonic oscillators sharing the same time-dependent frequency and subjected to similar noise mechanisms. Finally, our methodology can be used for the optimization of other interesting thermodynamic processes. PMID- 25122264 TI - Multiple phase transitions in extended hard-core lattice gas models in two dimensions. AB - We study the k-NN hard-core lattice gas model in which the first k next-nearest neighbor sites of a particle are excluded from occupation by other particles on a two-dimensional square lattice. This model is the lattice version of the hard disk system with increasing k corresponding to decreasing lattice spacing. While the hard-disk system is known to undergo a two-step freezing process with increasing density, the lattice model has been known to show only one transition. Here, based on Monte Carlo simulations and high-density expansions of the free energy and density, we argue that for k = 4,10,11,14,?, the lattice model undergoes multiple transitions with increasing density. Using Monte Carlo simulations, we confirm the same for k = 4,...,11. This, in turn, resolves an existing puzzle as to why the 4-NN model has a continuous transition against the expectation of a first-order transition. PMID- 25122265 TI - Quantum systems equilibrate rapidly for most observables. AB - Considering any Hamiltonian, any initial state, and measurements with a small number of possible outcomes compared to the dimension, we show that most measurements are already equilibrated. To investigate nontrivial equilibration, we therefore consider a restricted set of measurements. When the initial state is spread over many energy levels, and we consider the set of observables for which this state is an eigenstate, most observables are initially out of equilibrium yet equilibrate rapidly. Moreover, all two-outcome measurements, where one of the projectors is of low rank, equilibrate rapidly. PMID- 25122266 TI - Mean-field universality class induced by weak hyperbolic curvatures. AB - Order-disorder phase transition of the ferromagnetic Ising model is investigated on a series of two-dimensional lattices that have negative Gaussian curvatures. Exceptional lattice sites of coordination number seven are distributed on the triangular lattice, where the typical distance between the nearest exceptional sites is proportional to an integer parameter n. Thus, the corresponding curvature is asymptotically proportional to -n(-2). Spontaneous magnetization and specific heat are calculated by means of the corner transfer matrix renormalization group method. For all the finite n cases, we observe the mean field-like phase transition. It is confirmed that the entanglement entropy at the transition temperature is linear in (c/6)ln n, where c = 1/2 is the central charge of the Ising model. The fact agrees with the presence of the typical length scale n being proportional to the curvature radius. PMID- 25122267 TI - Fluctuations of isolated and confined surface steps of monatomic height. AB - The temporal evolution of equilibrium fluctuations for surface steps of monatomic height is analyzed studying one-dimensional solid-on-solid models. Using Monte Carlo simulations, fluctuations due to periphery diffusion (PD) as well as due to evaporation and condensation are considered, both for isolated steps and for steps confined by the presence of straight steps. For isolated steps, the dependence of the characteristic power laws, their exponents, and prefactors on temperature, slope, and curvature is elucidated, with the main emphasis on PD, taking into account finite-size effects. The entropic repulsion due to a second straight step may lead, among other things, to an interesting transient power-law like growth of the fluctuations, for PD. Findings are compared to results of previous Monte Carlo simulations and predictions based, mostly, on scaling arguments and Langevin theory. PMID- 25122268 TI - Numerical test of hydrodynamic fluctuation theory in the Fermi-Pasta-Ulam chain. AB - Recent work has developed a nonlinear hydrodynamic fluctuation theory for a chain of coupled anharmonic oscillators governing the conserved fields, namely, stretch, momentum, and energy. The linear theory yields two propagating sound modes and one diffusing heat mode, all three with diffusive broadening. In contrast, the nonlinear theory predicts that, at long times, the sound mode correlations satisfy Kardar-Parisi-Zhang scaling, while the heat mode correlations have Levy-walk scaling. In the present contribution we report on molecular dynamics simulations of Fermi-Pasta-Ulam chains to compute various spatiotemporal correlation functions and compare them with the predictions of the theory. We obtain very good agreement in many cases, but also some deviations. PMID- 25122269 TI - Reinterpretation of velocity-dependent atomic friction: influence of the inherent instrumental noise in friction force microscopes. AB - We have applied both the master equation method and harmonic transition state theory to interpret the velocity-dependent friction behavior observed in atomic friction experiments. To understand the discrepancy between attempt frequencies measured in atomic force microscopy experiments and those estimated by theoretical models, both thermal noise and instrumental noise are introduced into the model. It is found that the experimentally observed low attempt frequency and the transition point at low velocity regimes can be interpreted in terms of the instrumental noise inherent in atomic force microscopy. In contrast to previous models, this model also predicts (1) the existence of a two-slope curve of velocity dependence and (2) the decrease of critical velocity with temperature, which provides clues for further experimental verification of the influence of instrumental noise in friction measurements. PMID- 25122270 TI - Code-division multiple-access multiuser demodulator by using quantum fluctuations. AB - We examine the average-case performance of a code-division multiple-access (CDMA) multiuser demodulator in which quantum fluctuations are utilized to demodulate the original message within the context of Bayesian inference. The quantum fluctuations are built into the system as a transverse field in the infinite range Ising spin glass model. We evaluate the performance measurements by using statistical mechanics. We confirm that the CDMA multiuser modulator using quantum fluctuations achieve roughly the same performance as the conventional CDMA multiuser modulator through thermal fluctuations on average. We also find that the relationship between the quality of the original information retrieval and the amplitude of the transverse field is somehow a "universal feature" in typical probabilistic information processing, viz., in image restoration, error correcting codes, and CDMA multiuser demodulation. PMID- 25122271 TI - Strong local passivity in finite quantum systems. AB - Passive states of quantum systems are states from which no system energy can be extracted by any cyclic (unitary) process. Gibbs states of all temperatures are passive. Strong local (SL) passive states are defined to allow any general quantum operation, but the operation is required to be local, being applied only to a specific subsystem. Any mixture of eigenstates in a system-dependent neighborhood of a nondegenerate entangled ground state is found to be SL passive. In particular, Gibbs states are SL passive with respect to a subsystem only at or below a critical system-dependent temperature. SL passivity is associated in many body systems with the presence of ground state entanglement in a way suggestive of collective quantum phenomena such as quantum phase transitions, superconductivity, and the quantum Hall effect. The presence of SL passivity is detailed for some simple spin systems where it is found that SL passivity is neither confined to systems of only a few particles nor limited to the near vicinity of the ground state. PMID- 25122272 TI - Logarithmic finite-size effects on interfacial free energies: phenomenological theory and Monte Carlo studies. AB - The computation of interfacial free energies between coexisting phases (e.g., saturated vapor and liquid) by computer simulation methods is still a challenging problem due to the difficulty of an atomistic identification of an interface and interfacial fluctuations on all length scales. The approach to estimate the interfacial tension from the free-energy excess of a system with interfaces relative to corresponding single-phase systems does not suffer from the first problem but still suffers from the latter. Considering d-dimensional systems with interfacial area L(d-1) and linear dimension L(z) in the direction perpendicular to the interface, it is argued that the interfacial fluctuations cause logarithmic finite-size effects of order ln(L)/L(d-1) and order ln(L(z))/L(d-1), in addition to regular corrections (with leading-order const/L(d-1)). A phenomenological theory predicts that the prefactors of the logarithmic terms are universal (but depend on the applied boundary conditions and the considered statistical ensemble). The physical origin of these corrections are the translational entropy of the interface as a whole, "domain breathing" (coupling of interfacial fluctuations to the bulk order parameter fluctuations of the coexisting domains), and capillary waves. Using a new variant of the ensemble switch method, interfacial tensions are found from Monte Carlo simulations of d = 2 and d = 3 Ising models and a Lennard-Jones fluid. The simulation results are fully consistent with the theoretical predictions. PMID- 25122273 TI - Dynamic hysteretic features of Ising-type thin films. AB - In order to elucidate the nature of hysteresis characteristics in a magnetic Ising-type thin film with a certain thickness, such as types of frequency dispersion curves, decay of hysteresis loop area, corresponding coercive field and remanent magnetization values, etc., we investigate the hysteretic response of each layer within effective-field theory. Throughout the analysis, the best appropriate parameter values are chosen since they would allow us to observe the reversed magnetic hysteresis after a certain value of external field frequency. This eccentric phenomenon has prompted us to associate it to the domain nucleation and growth mechanism in the dynamic process. Exotic shapes of the response for different layer indices in two different regimes of modified surface exchange are particularly emphasized. PMID- 25122274 TI - Two-point resistance of a resistor network embedded on a globe. AB - We consider the problem of two-point resistance in an (m-1) * n resistor network embedded on a globe, a geometry topologically equivalent to an m * n cobweb with its boundary collapsed into one single point. We deduce a concise formula for the resistance between any two nodes on the globe using a method of direct summation pioneered by one of us [Z.-Z. Tan, L. Zhou, and J. H. Yang, J. Phys. A: Math. Theor. 46, 195202 (2013)]. This method is contrasted with the Laplacian matrix approach formulated also by one of us [F. Y. Wu, J. Phys. A: Math. Gen. 37, 6653 (2004)], which is difficult to apply to the geometry of a globe. Our analysis gives the result in the form of a single summation. PMID- 25122275 TI - Effects of cross-correlated noises on the transport of active Brownian particles. AB - The transport properties of active Brownian particles driven by cross-correlated noises are investigated. Using the Langevin and Fokker-Planck approaches, the theoretical analysis of the model is presented. It is found that correlated noises can produce a net velocity, which stems from the symmetric breaking of the system induced by the correlation between noises. The mean velocity is negative for positive correlation but positive for negative correlation. The mean velocity increases while the effective diffusion decreases as the absolute value of the correlation between the noises increases. Both the mean velocity and the effective diffusion show a nonmonotonic dependence on the multiplicative noise, but a monotonically decreasing dependence on the additive noise. PMID- 25122276 TI - Large pseudocounts and L2-norm penalties are necessary for the mean-field inference of Ising and Potts models. AB - The mean-field (MF) approximation offers a simple, fast way to infer direct interactions between elements in a network of correlated variables, a common, computationally challenging problem with practical applications in fields ranging from physics and biology to the social sciences. However, MF methods achieve their best performance with strong regularization, well beyond Bayesian expectations, an empirical fact that is poorly understood. In this work, we study the influence of pseudocount and L(2)-norm regularization schemes on the quality of inferred Ising or Potts interaction networks from correlation data within the MF approximation. We argue, based on the analysis of small systems, that the optimal value of the regularization strength remains finite even if the sampling noise tends to zero, in order to correct for systematic biases introduced by the MF approximation. Our claim is corroborated by extensive numerical studies of diverse model systems and by the analytical study of the m-component spin model for large but finite m. Additionally, we find that pseudocount regularization is robust against sampling noise and often outperforms L(2)-norm regularization, particularly when the underlying network of interactions is strongly heterogeneous. Much better performances are generally obtained for the Ising model than for the Potts model, for which only couplings incoming onto medium frequency symbols are reliably inferred. PMID- 25122277 TI - Exclusion processes with avalanches. AB - In an exclusion process with avalanches, when a particle hops to a neighboring empty site which is adjacent to an island the particle on the other end of the island immediately hops, and if it joins another island this triggers another hop. There are no restrictions on the length of the islands and the duration of the avalanche. This process is well defined in the low-density region rho < 1/2. We describe the nature of steady states (on a ring) and determine all correlation functions. For the asymmetric version of the process, we compute the steady state current, and we describe shock and rarefaction waves which arise in the evolution of the step-function initial profile. For the symmetric version, we determine the diffusion coefficient and examine the evolution of a tagged particle. PMID- 25122278 TI - Nonergodicity, fluctuations, and criticality in heterogeneous diffusion processes. AB - We study the stochastic behavior of heterogeneous diffusion processes with the power-law dependence D(x) ~ |x|(alpha) of the generalized diffusion coefficient encompassing sub- and superdiffusive anomalous diffusion. Based on statistical measures such as the amplitude scatter of the time-averaged mean-squared displacement of individual realizations, the ergodicity breaking and non Gaussianity parameters, as well as the probability density function P(x,t), we analyze the weakly nonergodic character of the heterogeneous diffusion process and, particularly, the degree of irreproducibility of individual realizations. As we show, the fluctuations between individual realizations increase with growing modulus |alpha| of the scaling exponent. The fluctuations appear to diverge when the critical value alpha = 2 is approached, while for even larger alpha the fluctuations decrease, again. At criticality, the power-law behavior of the mean squared displacement changes to an exponentially fast growth, and the fluctuations of the time-averaged mean-squared displacement do not converge for increasing number of realizations. From a systematic comparison we observe some striking similarities of the heterogeneous diffusion process with the familiar subdiffusive continuous time random walk process with power-law waiting time distribution and diverging characteristic waiting time. PMID- 25122279 TI - Kinetic Monte Carlo simulations of proton conductivity. AB - The kinetic Monte Carlo method is used to model the dynamic properties of proton diffusion in anhydrous proton conductors. The results have been discussed with reference to a two-step process called the Grotthuss mechanism. There is a widespread belief that this mechanism is responsible for fast proton mobility. We showed in detail that the relative frequency of reorientation and diffusion processes is crucial for the conductivity. Moreover, the current dependence on proton concentration has been analyzed. In order to test our microscopic model the proton transport in polymer electrolyte membranes based on benzimidazole C(7)H(6)N(2) molecules is studied. PMID- 25122280 TI - Emergence of limit-periodic order in tiling models. AB - A two-dimensional (2D) lattice model defined on a triangular lattice with nearest and next-nearest-neighbor interactions based on the Taylor-Socolar monotile is known to have a limit-periodic ground state. The system reaches that state during a slow quench through an infinite sequence of phase transitions. We study the model as a function of the strength of the next-nearest-neighbor interactions and introduce closely related 3D models with only nearest-neighbor interactions that exhibit limit-periodic phases. For models with no next-nearest-neighbor interactions of the Taylor-Socolar type, there is a large degenerate class of ground states, including crystalline patterns and limit-periodic ones, but a slow quench still yields the limit-periodic state. For the Taylor-Socolar lattic model, we present calculations of the diffraction pattern for a particular decoration of the tile that permits exact expressions for the amplitudes and identify domain walls that slow the relaxation times in the ordered phases. For one of the 3D models, we show that the phase transitions are first order, with equilibrium structures that can be more complex than in the 2D case, and we include a proof of aperiodicity for a geometrically simple tile with only nearest neighbor matching rules. PMID- 25122281 TI - Nonequilibrium dynamics of four-point correlations of collective density fluctuations in a supercooled liquid. AB - In this paper we study the four-point correlation function chi(4) of collective density fluctuations in a nonequilibrium liquid. The equilibration is controlled by a modified stretched exponential behavior (exp[-(t(w)/tau)(beta)]) having the relaxation time tau dependent on the aging time t(w). Similar aging behavior has been seen experimentally in supercooled liquids. The basic equations of fluctuating nonlinear hydrodynamics are solved here numerically to obtain chi(4) for equilibrium and non equilibrium states. We also identify a dynamic length scale xi from the equilibrated function. xi(T) grows with fall of temperature T. From a broader perspective, we demonstrate here that the characteristic signatures of dynamical heterogeneities in a supercooled liquid, observed previously in computer simulations of the dynamics of a small number of particles, are also present in the coarse grained equations of generalized hydrodynamics. PMID- 25122282 TI - Critical Casimir interactions between spherical particles in the presence of bulk ordering fields. AB - The spatial suppression of order parameter fluctuations in a critical media produces critical Casimir forces acting on confining surfaces. This scenario is realized in a critical binary mixture near the demixing transition point that corresponds to the second-order phase transition of the Ising universality class. Due to these critical interactions similar colloids, immersed in a critical binary mixture near the consolute point, exhibit attraction. The numerical method for computation of the interaction potential between two spherical particles using Monte Carlo simulations for the Ising model is proposed. This method is based on the integration of the local magnetization over the applied local magnetic field. For the stronger interaction the concentration of the component of the mixture that does not wet colloidal particles should be larger than the critical concentration. The strongest amplitude of the interactions is observed below the critical point. PMID- 25122283 TI - Rare regions and Griffiths singularities at a clean critical point: the five dimensional disordered contact process. AB - We investigate the nonequilibrium phase transition of the disordered contact process in five space dimensions by means of optimal fluctuation theory and Monte Carlo simulations. We find that the critical behavior is of mean-field type, i.e., identical to that of the clean five-dimensional contact process. It is accompanied by off-critical power-law Griffiths singularities whose dynamical exponent z' saturates at a finite value as the transition is approached. These findings resolve the apparent contradiction between the Harris criterion, which implies that weak disorder is renormalization-group irrelevant, and the rare region classification, which predicts unconventional behavior. We confirm and illustrate our theory by large-scale Monte Carlo simulations of systems with up to 70(5) sites. We also relate our results to a recently established general relation between the Harris criterion and Griffiths singularities [Phys. Rev. Lett. 112, 075702 (2014)], and we discuss implications for other phase transitions. PMID- 25122284 TI - One-dimensional disordered Ising models by replica and cavity methods. AB - Using a formalism based on the spectral decomposition of the replicated transfer matrix for disordered Ising models, we obtain several results that apply both to isolated one-dimensional systems and to locally treelike graph and factor graph (p-spin) ensembles. We present exact analytical expressions, which can be efficiently approximated numerically for many types of correlation functions and for the average free energies of open and closed finite chains. All the results achieved, with the exception of those involving closed chains, are then rigorously derived without replicas, using a probabilistic approach with the same flavor of cavity method. PMID- 25122285 TI - Structure and thermodynamic properties of relativistic electron gases. AB - Relativistic effect is important in many quantum systems but theoretically complicated from both fundamental and practical perspectives. Herein we introduce an efficient computational procedure to predict the structure and energetic properties of relativistic quantum systems by mapping the Pauli principle into an effective pairwise-additive potential such that the properties of relativistic nonquantum systems can be readily predicted from conventional liquid-state methods. We applied our theoretical procedure to relativistic uniform electron gases and compared the pair correlation functions with those for systems of nonrelativistic electrons. A simple analytical expression has been developed to correlate the exchange-correlation free energy of relativistic uniform electron systems. PMID- 25122286 TI - 1/ f noise from the laws of thermodynamics for finite-size fluctuations. AB - Computer simulations of the Ising model exhibit white noise if thermal fluctuations are governed by Boltzmann's factor alone; whereas we find that the same model exhibits 1/f noise if Boltzmann's factor is extended to include local alignment entropy to all orders. We show that this nonlinear correction maintains maximum entropy during equilibrium fluctuations. Indeed, as with the usual way to resolve Gibbs' paradox that avoids entropy reduction during reversible processes, the correction yields the statistics of indistinguishable particles. The correction also ensures conservation of energy if an instantaneous contribution from local entropy is included. Thus, a common mechanism for 1/f noise comes from assuming that finite-size fluctuations strictly obey the laws of thermodynamics, even in small parts of a large system. Empirical evidence for the model comes from its ability to match the measured temperature dependence of the spectral density exponents in several metals and to show non-Gaussian fluctuations characteristic of nanoscale systems. PMID- 25122287 TI - Condensation of fluctuations in and out of equilibrium. AB - Condensation of fluctuations is an interesting phenomenon conceptually distinct from condensation on average. One striking feature is that, contrary to what happens on average, condensation of fluctuations may occur even in the absence of interaction. The explanation emerges from the duality between large deviation events in the given system and typical events in a new and appropriately biased system. This phenomenon is investigated in the context of the Gaussian model, chosen as a paradigmatical noninteracting system, before and after an instantaneous temperature quench. It is shown that the bias induces a mean-field like effective interaction responsible for the condensation on average. Phase diagrams, covering both the equilibrium and the off-equilibrium regimes, are derived for observables representative of generic behaviors. PMID- 25122288 TI - Effect of disorder on condensation in the lattice gas model on a random graph. AB - The lattice gas model of condensation in a heterogeneous pore system, represented by a random graph of cells, is studied using an exact analytical solution. A binary mixture of pore cells with different coordination numbers is shown to exhibit two phase transitions as a function of chemical potential in a certain temperature range. Heterogeneity in interaction strengths is demonstrated to reduce the critical temperature and, for large-enough degreeS of disorder, divides the cells into ones which are either on average occupied or unoccupied. Despite treating the pore space loops in a simplified manner, the random-graph model provides a good description of condensation in porous structures containing loops. This is illustrated by considering capillary condensation in a structural model of mesoporous silica SBA-15. PMID- 25122289 TI - Work and efficiency of quantum Otto cycles in power-law trapping potentials. AB - We study the performance of a quantum Otto cycle operating in trapping potentials of different shapes. We show that, while both the mean work output and the efficiency of two Otto cycles in different trapping potentials can be made equal, the work probability distribution will still be strongly affected by the difference in structure of the energy levels. To exemplify our results, we study the family of potentials of the form V(t)(x) ~ x(2q). This family of potentials possesses a simple scaling property that allows for analytical insights into the efficiency and work output of the cycle. We perform a comparison of quantum Otto cycles in various physically relevant scenarios and find that in certain instances, the efficiency of the cycle is greater when using potentials with larger values of q, while in other cases, the efficiency is greater with harmonic traps. PMID- 25122290 TI - Finite-size corrections to disordered Ising models on random regular graphs. AB - We derive the analytical expression for the first finite-size correction to the average free energy of disordered Ising models on random regular graphs. The formula can be physically interpreted as a weighted sum over all non-self intersecting loops in the graph, the weight being the free-energy shift due to the addition of the loop to an infinite tree. PMID- 25122291 TI - Equilibrium time-correlation functions for one-dimensional hard-point systems. AB - As recently proposed, the long-time behavior of equilibrium time-correlation functions for one-dimensional systems are expected to be captured by a nonlinear extension of fluctuating hydrodynamics. We outline the predictions from the theory aimed at the comparison with molecular dynamics. We report on numerical simulations of a fluid with a hard-shoulder potential and of a hard-point gas with alternating masses. These models have in common that the collision time is zero and their dynamics amounts to iterating collision by collision. The theory is well confirmed, with the twist that the nonuniversal coefficients are still changing at longest accessible times. PMID- 25122292 TI - Heat transfer in the spin-boson model: a comparative study in the incoherent tunneling regime. AB - We study the transfer of heat in the nonequilibrium spin-boson model with an Ohmic dissipation. In the nonadiabatic limit we derive a formula for the thermal conductance based on a rate equation formalism at the level of the noninteracting blip approximation, valid for temperatures T>T(K), with T(K) as the Kondo temperature. We evaluate this expression analytically assuming either weak or strong couplings, and demonstrate that our results agree with exact relations. Far-from-equilibrium situations are further examined, showing a close correspondence to the linear response limit. PMID- 25122293 TI - Order-disorder transition in swirled granular disks. AB - We study the order-disorder transition of horizontally swirled dry and wet granular disks by means of computer simulations. Our systematic investigation of the local order formation as a function of amplitude and period of the external driving force shows that a large cluster of hexagonally ordered particles forms for both dry and wet granular particles at intermediate driving energies. Disordered states are found at small and large driving energies. Wet granular particles reach a higher degree of local hexagonal order with respect to the dry case. For both cases we report a qualitative phase diagram showing the amount of local order at different state points. Furthermore, we find that the transition from hexagonal order to a disordered state is characterized by the appearance of particles with square local order. PMID- 25122294 TI - Effect of size polydispersity versus particle shape in dense granular media. AB - We present a detailed analysis of the morphology of granular systems composed of frictionless pentagonal particles by varying systematically both the size span and particle shape irregularity, which represent two polydispersity parameters of the system. The microstructure is characterized in terms of various statistical descriptors such as global and local packing fractions, radial distribution functions, coordination number, and fraction of floating particles. We find that the packing fraction increases with the two parameters of polydispersity, but the effect of shape polydispersity for all the investigated structural properties is significant only at low size polydispersity where the positional and/or orientational ordering of the particles prevail. We focus in more detail on the class of side/side contacts, which is the interesting feature of our system as compared to a packing of disks. We show that the proportion of such contacts has weak dependence on the polydispersity parameters. The side- side contacts do not percolate but they define clusters of increasing size as a function of size polydispersity and decreasing size as a function of shape polydispersity. The clusters have anisotropic shapes but with a decreasing aspect ratio as polydispersity increases. This feature is argued to be a consequence of strong force chains (forces above the mean), which are mainly captured by side-side contacts. Finally, the force transmission is intrinsically multiscale, with a mean force increasing linearly with particle size. PMID- 25122295 TI - Granular flow through an aperture: influence of the packing fraction. AB - For the last 50 years, the flow of a granular material through an aperture has been intensely studied in gravity-driven vertical systems (e.g., silos and hoppers). Nevertheless, in many industrial applications, grains are horizontally transported at constant velocity, lying on conveyor belts or floating on the surface of flowing liquids. Unlike fluid flows, that are controlled by the pressure, granular flow is not sensitive to the local pressure but rather to the local velocity of the grains at the outlet. We can also expect the flow rate to depend on the local density of the grains. Indeed, vertical systems are packed in dense configurations by gravity, but, in contrast, in horizontal systems the density can take a large range of values, potentially very small, which may significantly alter the flow rate. In the present article, we study, for different initial packing fractions, the discharge through an orifice of monodisperse grains driven at constant velocity by a horizontal conveyor belt. We report how, during the discharge, the packing fraction is modified by the presence of the outlet, and we analyze how changes in the packing fraction induce variations in the flow rate. We observe that variations of packing fraction do not affect the velocity of the grains at the outlet, and, therefore, we establish that flow-rate variations are directly related to changes in the packing fraction. PMID- 25122296 TI - Memory effect in uniformly heated granular gases. AB - We evidence a Kovacs-like memory effect in a uniformly driven granular gas. A system of inelastic hard particles, in the low density limit, can reach a nonequilibrium steady state when properly forced. By following a certain protocol for the drive time dependence, we prepare the gas in a state where the granular temperature coincides with its long time value. The temperature subsequently does not remain constant but exhibits a nonmonotonic evolution with either a maximum or a minimum, depending on the dissipation and on the protocol. We present a theoretical analysis of this memory effect at Boltzmann-Fokker-Planck equation level and show that when dissipation exceeds a threshold, the response can be called anomalous. We find excellent agreement between the analytical predictions and direct Monte Carlo simulations. PMID- 25122297 TI - Electric double-layer potentials and surface regulation properties measured by colloidal-probe atomic force microscopy. AB - We show how the colloidal-probe technique, which is based on force measurements made with the atomic force microscope, can be used to accurately determine the charging parameters of water-solid interfaces. Besides yielding accurate values of the double-layer or diffuse-layer potential, the method also allows reliable determination of the charge regulation properties of the surfaces. The latter can be quantified with a regulation parameter, which is essential to properly describe forces between interfaces, especially in asymmetric situations when one of the interfaces is charged and the other one is close to neutral. The technique relies on a highly charged probe particle, for which the charging properties are accurately determined by interpreting the double-layer contribution of the measured force profiles in the symmetric sphere-sphere geometry with Poisson Boltzmann (PB) theory. Once the probe particle is calibrated, this particle is used to measure the force profile between an unknown substrate in the asymmetric sphere-sphere or sphere-plane geometry. From this profile, the diffuse-layer potential and regulation parameter of the substrate can be again determined with PB theory. The technique is highly versatile, as it can be used for a wide variety of substrates, including colloidal particles and planar substrates. The technique is also applicable in salt solutions containing multivalent ions. The current drawbacks of the technique are that it can only be applied up to moderately high salt levels, typically to 10 mM, and only for relatively large particles, typically down to about 1 MUm in diameter. How the technique could be extended to higher salt levels and smaller particle size is also briefly discussed. PMID- 25122298 TI - Directional locking in deterministic lateral-displacement microfluidic separation systems. AB - We analyze the trajectory of suspended spherical particles moving through a square array of obstacles, in the deterministic limit and at zero Reynolds number. We show that in the dilute approximation of widely separated obstacles, the average motion of the particles is equivalent to the trajectory followed by a point particle moving through an array of obstacles with an effective radius. The effective radius accounts for the hydrodynamic as well as short-range repulsive nonhydrodynamic interactions between the suspended particles and the obstacles, and is equal to the critical offset at which particle trajectories become irreversible. Using this equivalent system we demonstrate the presence of directional locking in the trajectory of the particles and derive an inequality that accurately describes the "devil's staircase" type of structure observed in the migration angle as a function of the forcing direction. We use these results to determine the optimum resolution in the fractionation of binary mixtures using deterministic lateral-displacement microfluidic separation systems as well as to comment on the collision frequencies when the arrays of posts are utilized as immunocapture devices. PMID- 25122299 TI - Diffusing-wave spectroscopy in an inhomogeneous object: local viscoelastic spectra from ultrasound-assisted measurement of correlation decay arising from the ultrasound focal volume. AB - We demonstrate diffusing-wave spectroscopy (DWS) in a localized region of a viscoelastically inhomogeneous object by measurement of the intensity autocorrelation [g(2)(tau)] that captures only the decay introduced by the temperature-induced Brownian motion in the region. The region is roughly specified by the focal volume of an ultrasound transducer which introduces region specific mechanical vibration owing to insonification. Essential characteristics of the localized non-Markovian dynamics are contained in the decay of the modulation depth [M(tau)], introduced by the ultrasound forcing in the focal volume selected, on g(2)(tau). The modulation depth M(tau(i)) at any delay time tau(i) can be measured by short-time Fourier transform of g(2)(tau) and measurement of the magnitude of the spectrum at the ultrasound drive frequency. By following the established theoretical framework of DWS, we are able to connect the decay in M(tau) to the mean-squared displacement (MSD) of scattering centers and the MSD to G*(omega), the complex viscoelastic spectrum. A two-region composite polyvinyl alcohol phantom with different viscoelastic properties is selected for demonstrating local DWS-based recovery of G*(omega) corresponding to these regions from the measured region specific M(tau(i))vstau(i). The ultrasound assisted measurement of MSD is verified by simulating, using a generalized Langevin equation (GLE), the dynamics of the particles in the region selected as well as by the usual DWS experiment without the ultrasound. It is shown that whereas the MSD obtained by solving the GLE without the ultrasound forcing agreed with its experimental counterpart covering small and large values of tau, the match was good only in the initial transients in regard to experimental measurements with ultrasound. PMID- 25122300 TI - Water electrolyte transport through corrugated carbon nanopores. AB - We investigate the effect of wall roughness on water electrolyte transport characteristics at different temperatures through carbon nanotubes by using nonequilibrium molecular dynamics simulations. Our results reveal that shearing stress and the nominal viscosity increase with ion concentration in corrugated carbon nanotubes (CNTs), in contrast to cases in smooth CNTs. Also, the temperature increase leads to the reduction of shearing stress and the nominal viscosity at moderate degrees of wall roughness. At high degrees of wall roughness, the temperature increase will enhance radial movements and increases resistance against fluid motion. As the fluid velocity increases, the particles do not have enough time to fully adjust their positions to minimize system energy, which causes shearing stress and the nominal viscosity to increase. By increasing roughness amplitude or decreasing roughness wavelength, the shearing stress will increase. Synergistic effects of such parameters (wall roughness, velocity, ion concentration, and temperature) inside corrugated CNTs are studied and compared with each other. The molecular mechanisms are considered by investigating the radial density profile and the radial velocity profile of confined water inside modified CNT. PMID- 25122301 TI - Phase behavior of a fluid with a double Gaussian potential displaying waterlike features. AB - Pair potentials that are bounded at the origin provide an accurate description of the effective interaction for many systems of dissolved soft macromolecules (e.g., flexible dendrimers). Using numerical free-energy calculations, we reconstruct the equilibrium phase diagram of a system of particles interacting through a potential that brings together a Gaussian repulsion with a much weaker Gaussian attraction, close to the thermodynamic stability threshold. Compared to the purely repulsive model, only the reentrant branch of the melting line survives, since for lower densities solidification is overridden by liquid-vapor separation. As a result, the phase diagram of the system recalls that of water up to moderate (i.e., a few tens of MPa) pressures. Upon superimposing a suitable hard core on the double-Gaussian potential, a further transition to a more compact solid phase is induced at high pressure, which might be regarded as the analog of the ice I-to-ice III transition in water. PMID- 25122302 TI - Influence of primary-particle density in the morphology of agglomerates. AB - Agglomeration processes occur in many different realms of science, such as colloid and aerosol formation or formation of bacterial colonies. We study the influence of primary-particle density in agglomerate structures using diffusion controlled Monte Carlo simulations with realistic space scales through different regimes (diffusion-limited aggregation and diffusion-limited colloid aggregation). The equivalence of Monte Carlo time steps to real time scales is given by Hirsch's hydrodynamical theory of Brownian motion. Agglomerate behavior at different time stages of the simulations suggests that three indices (the fractal exponent, the coordination number, and the eccentricity index) characterize agglomerate geometry. Using these indices, we have found that the initial density of primary particles greatly influences the final structure of the agglomerate, as observed in recent experimental works. PMID- 25122303 TI - Self-propelled particle transport in regular arrays of rigid asymmetric obstacles. AB - We report numerical results which show the achievement of net transport of self propelled particles (SPPs) in the presence of a two-dimensional regular array of convex, either symmetric or asymmetric, rigid obstacles. The repulsive interparticle (soft disks) and particle-obstacle interactions present no alignment rule. We find that SPPs present a vortex-type motion around convex symmetric obstacles even in the absence of hydrodynamic effects. Such a motion is not observed for a single SPP, but is a consequence of the collective motion of SPPs around the obstacles. A steady particle current is spontaneously established in an array of nonsymmetric convex obstacles (which presents no cavity in which particles may be trapped), and in the absence of an external field. Our results are mainly a consequence of the tendency of the self-propelled particles to attach to solid surfaces. PMID- 25122304 TI - Model for a mixture of macroions, counterions, and co-ions in a waterlike fluid. AB - We propose an integral equation theory for a mixture of macroions, counterions, and co-ions in a waterlike fluid in which all the components are accounted for explicitly. The macroions can carry positive and negative surface charges simultaneously, mimicking in this way the situation occurring in protein solutions. To solve this complex model numerically, we utilize the associative mean spherical approximation, developed earlier for low-molecular-mass charge symmetric electrolyte solutions. To illustrate the potential of this approach, we present numerical results for various experimental conditions. Among the measurable properties we choose to calculate the osmotic coefficient, a quantity that reflects the stability of the solution. We show that the osmotic coefficient depends not only on the magnitude of the net charge on the macroion but also on its sign, as well as on the nature of the low-molecular-mass electrolyte present. These specific ion effects are the consequence of differences in hydration between the ions in solution and charged groups on the macroion. PMID- 25122305 TI - Characteristics of angular cross correlations studied by light scattering from two-dimensional microsphere films. AB - Recently the analysis of scattering patterns by angular cross-correlation analysis (CCA) was introduced to reveal the orientational order in disordered samples with special focus to future applications on x-ray free-electron laser facilities. We apply this CCA approach to ultra-small-angle light-scattering data obtained from two-dimensional monolayers of microspheres. The films were studied in addition by optical microscopy. This combined approach allows to calculate the cross-correlations of the scattering patterns, characterized by the orientational correlation function Psi(l)(q), as well as to obtain the real-space structure of the monolayers. We show that CCA is sensitive to the orientational order of monolayers formed by the microspheres which are not directly visible from the scattering patterns. By mixing microspheres of different radii the sizes of ordered monolayer domains is reduced. For these samples it is shown that Psi(l)(q) quantitatively describes the degree of hexagonal order of the two dimensional films. The experimental CCA results are compared with calculations based on the microscopy images. Both techniques show qualitatively similar features. Differences can be attributed to the wave-front distortion of the laser beam in the experiment. This effect is discussed by investigating the effect of different wave fronts on the cross-correlation analysis results. The so determined characteristics of the cross-correlation analysis will be also relevant for future x-ray-based studies. PMID- 25122306 TI - How nonmagnetic particles intensify rotational diffusion in magnetorheological fluids. AB - In this work we propose a mechanism to explain the enhancement of the magnetic field-induced yield stress when nonmagnetic particles are added to magnetic particulate suspensions, i.e., two-component suspensions. Our main hypothesis is that the nonmagnetic particles collide with the field-induced magnetic aggregates under shear flow. Consequently, supplementary fluctuations of the orientations of the magnetic aggregates occur, resulting in an effective rotary diffusion process, which increases the dynamic yield stress of the suspension. Furthermore, the collision rate and the rotary diffusivity of the aggregates should increase with the concentration of nonmagnetic particles. Rheological measurements in plate-plate and cylindrical Couette geometries confirm the increase of the yield stress with the volume fraction of nonmagnetic particles. In addition, such an effect appears to be more important in Couette geometry, for which orientation fluctuations of the magnetic aggregates play a more significant role. Finally, a theoretical model based on this rotary diffusion mechanism is developed, providing a quantitative explanation of the experimentally observed trends. PMID- 25122307 TI - Surface shear-transformation zones in amorphous solids. AB - We perform a systematic study of the characteristics of shear transformation zones (STZs) that nucleate at free surfaces of two-dimensional amorphous solids subject to tensile loading using two different atomistic simulation methods, the standard athermal, quasistatic (AQ) approach and our recently developed self learning metabasin escape (SLME) method, to account for the finite temperature and strain-rate effects. In the AQ, or strain-driven limit, the nonaffine displacement fields of surface STZs decay exponentially away from their centers at similar decay rates as their bulk counterparts, though the direction of maximum nonaffine displacement is tilted away from the tensile axis due to surface effects. Using the SLME method at room temperature and at the high strain rates that are seen in classical molecular dynamics simulations, the characteristics for both bulk and surface STZs are found to be identical to those seen in the AQ simulations. However, using the SLME method at room temperature and experimentally relevant strain rates, we find a transition in the surface STZ characteristics where a loss in the characteristic angular tensile-compression symmetry is observed. Finally, the thermally activated surface STZs exhibit a slower decay rate in the nonaffine displacement field than do strain-driven surface STZs, which is characterized by a larger drop in potential energy resulting from STZ nucleation that is enabled by the relative compliance of the surface as compared to the bulk. PMID- 25122308 TI - Interplay of model ingredients affecting aggregate shape plasticity in diffusion limited aggregation. AB - We analyze the combined effect of three ingredients of an aggregation model- surface tension, particle flow and particle source--representing typical characteristics of many aggregation growth processes in nature. Through extensive numerical experiments and for different underlying lattice structures we demonstrate that the location of incoming particles and their preferential direction of flow can significantly affect the resulting general shape of the aggregate, while the surface tension controls the surface roughness. Combining all three ingredients increases the aggregate shape plasticity, yielding a wider spectrum of shapes as compared to earlier works that analyzed these ingredients separately. Our results indicate that the considered combination of effects is fundamental for modeling the polymorphic growth of a wide variety of structures in confined geometries and/or in the presence of external fields, such as rocks, crystals, corals, and biominerals. PMID- 25122309 TI - Phase-field modeling of grain-boundary premelting using obstacle potentials. AB - We investigate the multiorder parameter phase field model of Steinbach and Pezzolla [Physica D 134, 385 (1999)] concerning its ability to describe grain boundary premelting. For a single order parameter situation solid-melt interfaces are always attractive, which allows us to have (unstable) equilibrium solid-melt solid coexistence above the bulk melting point. The temperature-dependent melt layer thickness and the disjoining potential, which describe the interface interaction, are affected by the choice of the thermal coupling function and the measure to define the amount of the liquid phase. Due to the strictly finite interface thickness the interaction range also is finite. For a multiorder parameter model we find either purely attractive or purely repulsive finite ranged interactions. The premelting transition is then directly linked to the ratio of the grain boundary and solid-melt interfacial energy. PMID- 25122310 TI - Thermally activated depinning motion of contact lines in pseudopartial wetting. AB - We investigate pressure-driven motion of liquid-liquid menisci in circular tubes, for systems in pseudopartial wetting conditions. The originality of this type of wetting lies in the coexistence of a macroscopic contact angle with a wetting liquid film covering the solid surface. Focusing on small capillary numbers, we report observations of an apparent contact angle hysteresis at first sight similar to the standard partial wetting case. However, this apparent hysteresis exhibits original features. We observe very long transient regimes before steady state, up to several hundreds of seconds. Furthermore, in steady state, the velocities are nonzero, meaning that the contact line is not strongly pinned to the surface defects, but are very small. The velocity of the contact line tends to vanish near the equilibrium contact angle. These observations are consistent with the thermally activated depinning theory that has been proposed to describe partial wetting systems on disordered substrates and suggest that a single physical mechanism controls both the hysteresis (or the pinning) and the motion of the contact line. The proposed analysis leads to the conclusion that the depinning activated energy is lower with pseudopartial wetting systems than with partial wetting ones, allowing the direct observation of the thermally activated motion of the contact line. PMID- 25122311 TI - Self-similarity and scaling of thermal shock fractures. AB - The problem of crack pattern formation due to thermal shock loading at the surface of half space is solved numerically using the two-dimensional boundary element method. The results of numerical simulations with 100-200 random simultaneously growing and interacting cracks are used to obtain scaling relations for crack length and spacing. The numerical results predict that such a process of pattern formation with quasistatic crack growth is not stable and at some point the excess energy leads to unstable propagation of one of the longest cracks. This single-crack scenario should be understood in a local sense. There could be other unstable cracks far away that together can form a new pattern. The onset of instability has also been determined from numerical results. PMID- 25122312 TI - Boundary lubrication with a liquid crystal monolayer. AB - We study boundary lubrication characteristics of a liquid crystal (LC) monolayer sheared between two crystalline surfaces by nonequilibrium molecular dynamics simulations, using a simplified rigid bead-necklace model of the LC molecules. We consider LC monolayers confined by surfaces with three different atomic structures, subject to different shearing velocities, thus approximating a wide variety of materials and driving conditions. The time dependence of the friction force is studied and correlated with that of the orientational order exhibited by the LC molecules, arising from the competition between the effect of the structure of the confining surfaces and that of the imposed sliding direction. We show that the observed stick-slip events for low shear rates involve order disorder transitions, and that the LC monolayer no longer has enough time to reorder at high shear rates, resulting in a smooth sliding regime. An irregular stick-slip phase between the regular stick-slip and smooth sliding is observed for intermediate shear rates regardless of the surface structure. PMID- 25122313 TI - High-speed atomic force microscope imaging: adaptive multiloop mode. AB - In this paper, an imaging mode (called the adaptive multiloop mode) of atomic force microscope (AFM) is proposed to substantially increase the speed of tapping mode (TM) imaging while preserving the advantages of TM imaging over contact mode (CM) imaging. Due to its superior image quality and less sample disturbances over CM imaging, particularly for soft materials such as polymers, TM imaging is currently the most widely used imaging technique. The speed of TM imaging, however, is substantially (over an order of magnitude) lower than that of CM imaging, becoming the major bottleneck of this technique. Increasing the speed of TM imaging is challenging as a stable probe tapping on the sample surface must be maintained to preserve the image quality, whereas the probe tapping is rather sensitive to the sample topography variation. As a result, the increase of imaging speed can quickly lead to loss of the probe-sample contact and/or annihilation of the probe tapping, resulting in image distortion and/or sample deformation. The proposed adaptive multiloop mode (AMLM) imaging overcomes these limitations of TM imaging through the following three efforts integrated together: First, it is proposed to account for the variation of the TM deflection when quantifying the sample topography; second, an inner-outer feedback control loop to regulate the TM deflection is added on top of the tapping-feedback control loop to improve the sample topography tracking; and, third, an online iterative feedforward controller is augmented to the whole control system to further enhance the topography tracking, where the next-line sample topography is predicted and utilized to reduce the tracking error. The added feedback regulation of the TM deflection ensures the probe-sample interaction force remains near the minimum for maintaining a stable probe-sample interaction. The proposed AMLM imaging is tested and demonstrated by imaging a poly(tert-butyl acrylate) sample in experiments. The experimental results demonstrate that the image quality achieved by using the proposed AMLM imaging at a scan rate of 25 Hz and over a large-size imaging (50 MUm * 25 MUm) is at the same level of that obtained using TM imaging at 1 Hz, while the probe-sample interaction force is noticeably reduced from that achieved using TM imaging at 2.5 Hz. PMID- 25122314 TI - Contact angle hysteresis and pinning at periodic defects in statics. AB - This article deals with the theoretical prediction of the wetting hysteresis on nonideal solid surfaces in terms of the surface heterogeneity parameters. The spatially periodical chemical heterogeneity is considered. We propose precise definitions for both the advancing and the receding contact angles for the Wilhelmy plate geometry. It is well known that in such a system, a multitude of metastable states of the liquid meniscus occurs for each different relative position of the defect pattern on the plate with respect to the liquid level. As usual, the static advancing and receding angles are assumed to be a consequence of the preceding contact line motion in the respective direction. It is shown how to select the appropriate states among all metastable states. Their selection is discussed. The proposed definitions are applicable to both the static and the dynamic contact angles on heterogeneous surfaces. The static advancing and receding angles are calculated for two examples of periodic heterogeneity patterns with sharp borders: the horizontal alternating stripes of a different wettability (studied analytically) and the doubly periodic pattern of circular defects on a homogeneous base (studied numerically). The wetting hysteresis is determined as a function of the defect density and the spatial period. A comparison with the existing results is carried out. PMID- 25122315 TI - Sharp interfaces in two-dimensional free boundary problems: interface calculation via matched conformal maps. AB - We use conformal maps to study a free boundary problem for a two-fluid electromechanical system, where the interface between the fluids is determined by the combined effects of electrostatic forces, gravity, and surface tension. The free boundary in our system develops sharp corners or singularities in certain parameter regimes, and this is an impediment to using existing "single-scale" numerical conformal mapping methods. The difficulty is due to the phenomenon of crowding, i.e., the tendency of nodes in the preimage plane to concentrate near the sharp regions of the boundary, leaving the smooth regions of the boundary poorly resolved. A natural idea is to exploit the scale separation between the sharp regions and smooth regions to solve for each region separately and then stitch the solutions together. However, this is not straightforward as conformal maps are rigid "global" objects, and it is not obvious how one would patch two conformal maps together to obtain a new conformal map. We develop a "multiscale" (i.e., adaptive) conformal mapping method that allows us to carry out this program of stitching conformal maps on different scales together. We successfully apply our method to the electromechanical model problem. PMID- 25122316 TI - Damage accumulation in quasibrittle fracture. AB - The strength of quasibrittle materials depends on the ensemble of defects inside the sample and on the way damage accumulates before failure. Using large-scale numerical simulations of the random fuse model, we investigate the evolution of the microcrack distribution as the applied load approaches the fracture point. We find that the distribution broadens mostly due to a tendency of cracks to coalesce in a way that increases with system size. We study how the observed behavior depends on the disorder present in the sample and relate the results with fracture size effects. PMID- 25122317 TI - Dewetting of evaporating thin films over nanometer-scale topographies. AB - A lubrication model is used to study dewetting of an evaporating thin film layer over a solid substrate with a nanometer-scale topography. The effects of the geometry of the topography, the contact angle, the film thickness, and the slippage on the dewetting have been studied. Our results reveal that the evaporation enhances the dewetting process and reduces the depinning time over the topography. Also it is shown that the depinning time is inversely proportional to the slippage and increasing the contact angle may considerably reduce the depinning time, while the film thickness increases the depinning time. PMID- 25122318 TI - Equilibrium configurations of nematic liquid crystals on a torus. AB - The topology and the geometry of a surface play a fundamental role in determining the equilibrium configurations of thin films of liquid crystals. We propose here a theoretical analysis of a recently introduced surface Frank energy, in the case of two-dimensional nematic liquid crystals coating a toroidal particle. Our aim is to show how a different modeling of the effect of extrinsic curvature acts as a selection principle among equilibria of the classical energy and how new configurations emerge. In particular, our analysis predicts the existence of stable equilibria with complex windings. PMID- 25122319 TI - Dynamics of colloidal particles in electrohydrodynamic convection of nematic liquid crystal. AB - We have studied the dynamics of micrometer-sized colloidal particles in electrohydrodynamic convection of nematic liquid crystal. Above the onset voltage of electroconvection, the parallel array of convection rolls appears to be perpendicular to the nematic field at first. The particles are forced to rotate by convection flow and are trapped within a single roll in this voltage regime. A slow glide motion along the roll axis is also observed. The frequency of rotational motion and the glide velocity increase with the applied voltage. Under a much larger voltage where the roll axis temporally fluctuates, the particles occasionally hop to the neighbor rolls. In this voltage regime, the motion of the particles becomes two-dimensional. The motion perpendicular to the roll axis exhibits diffusion behavior at a long time period. The effective diffusion constant is 10(3)-10(4) times larger than the molecular one. The observed behavior is compared with the result obtained by a simple stochastic model for the transport of the particles in convection. The enhancement of diffusion can be quantitatively described well by the rotation frequency in a roll, the width of the roll, and the hopping probability to the neighbor rolls. PMID- 25122320 TI - Electric-field variations within a nematic-liquid-crystal layer. AB - A thin layer of nematic liquid crystal (NLC) across which an electric field is applied is a setup of great industrial importance in liquid crystal display devices. There is thus a large literature modeling this situation and related scenarios. A commonly used assumption is that an electric field generated by electrodes at the two bounding surfaces of the layer will produce a field that is uniform: that is, the presence of NLC does not affect the electric field. In this paper, we use calculus of variations to derive the equations coupling the electric potential to the orientation of the NLC's director field, and use a simple one-dimensional model to investigate the limitations of the uniform field assumption in the case of a steady applied field. The extension of the model to the unsteady case is also briefly discussed. PMID- 25122321 TI - Gold nanoparticle liquid crystal composites as a tunable nonlinear medium. AB - We investigate the nonlinearity of a liquid crystal cell doped with gold nanoparticles by considering their selective absorption. Such nonlinearities are promising for optical processing applications and optical limiters. Systems displaying thermal nonlinearities are particularly attractive as the maximum nonlinearity may occur in the absence of an applied field and additionally this nonlinearity can be controlled by the reorientation of the liquid crystal. We show that there exists a theoretical optimum concentration of absorbers, which maximizes the nonlinearity. Further we show that the nonlinearity of the system can be tuned by the reorientation of the liquid crystal host, with the nonlinearity decreasing from 9 * 10(-5) cm(2)W(-1) to zero by the application of a magnetic field of the order of 0.01 Tesla. This allows a fine control of the diffraction efficiency and, in principle, many other nonlinear effects. PMID- 25122322 TI - Two-dimensional skyrmions and other solitonic structures in confinement frustrated chiral nematics. AB - We explore spatially localized solitonic configurations of a director field, generated using optical realignment and laser-induced heating, in frustrated chiral nematic liquid crystals confined between substrates with perpendicular surface anchoring. We demonstrate that, in addition to recently studied torons and Hopf-fibration solitonic structures (hopfions), one can generate a host of other axially symmetric stable and metastable director field configurations where local twist is matched to the surface boundary conditions through introduction of point defects and loops of singular and nonsingular disclinations. The experimentally demonstrated structures include the so-called "baby-skyrmions" in the form of double twist cylinders oriented perpendicular to the confining substrates where their double twist field configuration is matched to the perpendicular boundary conditions by loops of twist disclinations. We also generate complex textures with arbitrarily large skyrmion numbers. A simple back of-the-envelope theoretical analysis based on free energy considerations and the nonpolar nature of chiral nematics provides insights into the long-term stability and diversity of these inter-related solitonic field configurations, including different types of torons, cholestric-finger loops, two-dimensional skyrmions, and more complex structures comprised of torons, hopfions, and various disclination loops that are experimentally observed in a confinement-frustrated chiral nematic system. PMID- 25122323 TI - Rheology of twist-grain-boundary-A liquid crystals. AB - We report studies on the rheological properties of a liquid crystalline analog of Abrikosov phase in type-II superconductors known as twist-grain-boundary-A (TGB(A)) phase. The TGB(A) phase shows a large apparent yield stress compared to the cholesteric (N*) phase. The storage modulus (G') of the TGB(A) phase is significantly larger than the loss modulus (G''). The dynamic relaxation measurements indicate a solid-like behavior of N*, TGB(A), and smectic-C* phases. The complex shear modulus of the TGB(A) phase exhibits a power-law behavior G*(omega) ~ omega(alpha) with alpha ? 0.5. The relative amplitude of G' and G'' at various temperatures indicate that the enhanced elasticity of TGB(A) phase is due to the structural defects. PMID- 25122324 TI - Symmetry breaking of nematic umbilical defects through an amplitude equation. AB - The existence, stability properties, and bifurcation diagram of the nematic umbilical defects is studied. Close to the Freedericksz transition of nematic liquid crystals with negative anisotropic dielectric constant and homeotropic anchoring, an anisotropic Ginzburg-Landau equation for the amplitude of the tilt of the director away from the vertical axis is derived by taking the three dimensional (3D) to 2D limit of the Frank-Oseen model. The anisotropic Ginzburg Landau equation allows us to reveal the mechanism of symmetry breaking of nematic umbilical defects. The positive defect is fully characterized as a function of the anisotropy, while the negative defect is characterized perturbatively. Numerical simulations show quite good agreement with the analytical results. PMID- 25122325 TI - Comparative studies on field-induced stretching behavior of single-walled and multiwalled carbon nanotube clusters. AB - We demonstrate distinct entanglement of single-walled carbon nanotube (SWCNT) and multiwalled carbon nanotube (MWCNT) clusters in nematic liquid crystal medium using scanning electron microscopy technique and the entanglement influence on electric field-induced stretching phenomena of the said clusters in the same medium under optical microscopy investigation. The observed stretching threshold field for MWCNT clusters is found to be higher than the SWCNT counterpart caused by the interplay between attractive field-induced dipolar interaction of intercarbon nanotube (CNT) bundles and the distinct degree of entanglement of neighboring CNT bundles. Subsequently observed different tensile elasticity modulus results for different CNT kinds also confirm different CNT bundle entanglement and attractive dipolar interaction between adjacent CNT bundles in CNT clusters are responsible for distinct stretching threshold field behavior. PMID- 25122326 TI - Coarse-grained molecular dynamics simulations of the tensile behavior of a thermosetting polymer. AB - Using a previously developed coarse-grained model, we conducted large-scale (~ 85 * 85 * 85 nm(3)) molecular dynamics simulations of uniaxial-strain deformation to study the tensile behavior of an epoxy molding compound, epoxy phenol novolacs (EPN) bisphenol A (BPA). Under the uniaxial-strain deformation, the material is found to exhibit cavity nucleation and growth, followed by stretching of the ligaments separated by the cavities, until the ultimate failure through ligament scissions. The nucleation sites of cavities are rather random and the subsequent cavity growth accounts for much (87%) of the volumetric change during the uniaxial-strain deformation. Ultimate failure of the materials occurs when the cavity volume fraction reaches ~ 60%. During the entire deformation process, polymer strands in the network are continuously extended to their linear states and broken in the postyielding strain hardening stage. When most of the strands are stretched to their taut configurations, rapid scission of a large number of strands occurs within a small strain increment, which eventually leads to fracture. Finally, through extensive numerical simulations of various loading conditions in addition to uniaxial strain, we find that yielding of the EPN-BPA can be described by the pressure-modified von Mises yield criterion. PMID- 25122327 TI - Healing of polymer interfaces: Interfacial dynamics, entanglements, and strength. AB - Self-healing of polymer films often takes place as the molecules diffuse across a damaged region, above their melting temperature. Using molecular dynamics simulations we probe the healing of polymer films and compare the results with those obtained for thermal welding of homopolymer slabs. These two processes differ from each other in their interfacial structure since damage leads to increased polydispersity and more short chains. A polymer sample was cut into two separate films that were then held together in the melt state. The recovery of the damaged film was followed as time elapsed and polymer molecules diffused across the interface. The mass uptake and formation of entanglements, as obtained from primitive path analysis, are extracted and correlated with the interfacial strength obtained from shear simulations. We find that the diffusion across the interface is significantly faster in the damaged film compared to welding because of the presence of short chains. Though interfacial entanglements increase more rapidly for the damaged films, a large fraction of these entanglements are near chain ends. As a result, the interfacial strength of the healing film increases more slowly than for welding. For both healing and welding, the interfacial strength saturates as the bulk entanglement density is recovered across the interface. However, the saturation strength of the damaged film is below the bulk strength for the polymer sample. At saturation, cut chains remain near the healing interface. They are less entangled and as a result they mechanically weaken the interface. Chain stiffness increases the density of entanglements, which increases the strength of the interface. Our results show that a few entanglements across the interface are sufficient to resist interfacial chain pullout and enhance the mechanical strength. PMID- 25122328 TI - Electrets in soft materials: nonlinearity, size effects, and giant electromechanical coupling. AB - Development of soft electromechanical materials is critical for several tantalizing applications such as soft robots and stretchable electronics, among others. Soft nonpiezoelectric materials can be coaxed to behave like piezoelectrics by merely embedding charges and dipoles in their interior and assuring some elastic heterogeneity. Such so-called electret materials have been experimentally shown to exhibit very large electromechanical coupling. In this work, we derive rigorous nonlinear expressions that relate effective electromechanical coupling to the creation of electret materials. In contrast to the existing models, we are able to both qualitatively and quantitatively capture the known experimental results on the nonlinear response of electret materials. Furthermore, we show that the presence of another form of electromechanical coupling, flexoelectricity, leads to size effects that dramatically alter the electromechanical response at submicron feature sizes. One of our key conclusions is that nonlinear deformation (prevalent in soft materials) significantly enhances the flexoelectric response and hence the aforementioned size effects. PMID- 25122329 TI - Active matter transport and jamming on disordered landscapes. AB - We numerically examine the transport of active run-and-tumble particles with steric particle-particle interactions driven with a drift force over random disordered landscapes composed of fixed obstacles. For increasing run lengths, the net particle transport initially increases before reaching a maximum and decreasing at larger run lengths. The transport reduction is associated with the formation of cluster or living crystal states that become locally jammed or clogged by the obstacles. We also find that the system dynamically jams at lower particle densities when the run length is increased. Our results indicate that there is an optimal activity level for transport of run-and-tumble type active matter through quenched disorder and could be important for understanding biological transport in complex environments or for applications of active matter particles in random media. PMID- 25122330 TI - Linear noise approximation for oscillations in a stochastic inhibitory network with delay. AB - Understanding neural variability is currently one of the biggest challenges in neuroscience. Using theory and computational modeling, we study the behavior of a globally coupled inhibitory neural network, in which each neuron follows a purely stochastic two-state spiking process. We investigate the role of both this intrinsic randomness and the conduction delay on the emergence of fast (e.g., gamma) oscillations. Toward that end, we expand the recently proposed linear noise approximation (LNA) technique to this non-Markovian "delay" case. The analysis first leads to a nonlinear delay-differential equation (DDE) with multiplicative noise for the mean activity. The LNA then yields two coupled DDEs, one of which is driven by additive Gaussian white noise. These equations on their own provide an excellent approximation to the full network dynamics, which are much longer to integrate. They further allow us to compute a theoretical expression for the power spectrum of the population activity. Our analytical result is in good agreement with the power spectrum obtained via numerical simulations of the full network dynamics, for the large range of parameters where both the intrinsic stochasticity and the conduction delay are necessary for the occurrence of oscillations. The intrinsic noise arises from the probabilistic description of each neuron, yet it is expressed at the system activity level, and it can only be controlled by the system size. In fact, its effect on the fluctuations in system activity disappears in the infinite network size limit, but the characteristics of the oscillatory activity depend on all model parameters including the system size. Using the Hilbert transform, we further show that the intrinsic noise causes sporadic strong fluctuations in the phase of the gamma rhythm. PMID- 25122331 TI - Reconstruction of network structures from repeating spike patterns in simulated bursting dynamics. AB - Repeating patterns of spike sequences from a neuronal network have been proposed to be useful in the reconstruction of the network topology. Reverberations in a physiologically realistic model with various physical connection topologies (from random to scale free) have been simulated to study the effectiveness of the pattern-matching method in the reconstruction of network topology from network dynamics. Simulation results show that functional networks reconstructed from repeating spike patterns can be quite different from the original physical networks; even global properties, such as the degree distribution, cannot always be recovered. However, the pattern-matching method can be effective in identifying hubs in the network. Since the form of reverberations is quite different for networks with and without hubs, the form of reverberations together with the reconstruction by repeating spike patterns might provide a reliable method to detect hubs in neuronal cultures. PMID- 25122332 TI - Swimming efficiency of spherical squirmers: beyond the Lighthill theory. AB - Nonreciprocal shape deformations can drive inertialess cellular swimming, as first explored by Taylor and Lighthill in the 1950s, for the small-amplitude squirming of a planar and a spherical surface, respectively. Lighthill's squirmer, in particular, has been extensively studied for large wave numbers in the context of ciliated microbes. The maximal power efficiency for small amplitude planar squirming motility is well characterized and degenerate, with nonunique optimal swimming strokes. We explicitly show that this degeneracy is retained at high wave numbers for the small-amplitude spherical squirmer such as a ciliated microbe but is broken for low wave numbers. Hence further complexity emerges in parameter regimes outside that of ciliate swimming even at small amplitudes. Large-amplitude squirming also characterizes more recent observations of large-amplitude/low-wave-number membrane deformations driving the motility of Euglena, neutrophils, and Dictyostelium discoideum. Thus boundary element numerical methods are used to explore swimming with increased deformation amplitudes, especially in the context of power efficiency and swimming performance. As radial squirming amplitudes are increased, small-amplitude linearized theories can be unreliable even for nominally low deformation amplitudes. Furthermore, even for a simple single-mode metachronal wave, a highly motile and efficient large-deformation/small-wave-number swimming modality arises, which can surpass theoretical limitations of purely tangential squirming given a constrained surface deformation velocity. PMID- 25122333 TI - Numerical simulation of the pairwise interaction of deformable cells during migration in a microchannel. AB - Leukocytes and other circulating cells deform and move relatively to the channel flow in the lateral and translational directions. Their migratory property is important in immune response, hemostasis, cancer progression, delivery of nutrients, and microfluidic technologies such as cell separation and enrichment, and flow cytometry. Using our three-dimensional computational algorithm for multiphase viscoelastic flow, we have investigated the effect of pairwise interaction on the lateral and translational migration of circulating cells in a microchannel. The numerical simulation data show that when two cells with the same size and small separation distance interact, repulsive interaction take place until they reach the same lateral equilibrium position. During this process, they undergo swapping or passing, depending on the initial separation distance between each other. The threshold value of this distance increases with cell deformation, indicating that the cells experiencing larger deformation are more likely to swap. When a series of closely spaced cells with the same size are considered, they generally undergo damped oscillation in both lateral and translational directions until they reach equilibrium positions where they become evenly distributed in the flow direction (self-assembly phenomenon). A series of cells with a large lateral separation distance could collide repeatedly with each other, eventually crossing the centerline and entering the other side of the channel. For a series of cells with different deformability, more deformable cells, upon impact with less deformable cells, move to an equilibrium position closer to the centerline. The results of our study show that the bulk deformation of circulating cells plays a key role in their migration in a microchannel. PMID- 25122334 TI - Control of cardiac alternans by mechanical and electrical feedback. AB - A persistent alternation in the cardiac action potential duration has been linked to the onset of ventricular arrhythmia, which may lead to sudden cardiac death. A coupling between these cardiac alternans and the intracellular calcium dynamics has also been identified in previous studies. In this paper, the system of PDEs describing the small amplitude of alternans and the alternation of peak intracellular Ca(2+) are stabilized by optimal boundary and spatially distributed actuation. A simulation study demonstrating the successful annihilation of both alternans on a one-dimensional cable of cardiac cells by utilizing the full-state feedback controller is presented. Complimentary to these studies, a three variable Nash-Panfilov model is used to investigate alternans annihilation via mechanical (or stretch) perturbations. The coupled model includes the active stress which defines the mechanical properties of the tissue and is utilized in the feedback algorithm as an independent input from the pacing based controller realization in alternans annihilation. Simulation studies of both control methods demonstrate that the proposed methods can successfully annihilate alternans in cables that are significantly longer than 1 cm, thus overcoming the limitations of earlier control efforts. PMID- 25122336 TI - Inferring the origin of an epidemic with a dynamic message-passing algorithm. AB - We study the problem of estimating the origin of an epidemic outbreak: given a contact network and a snapshot of epidemic spread at a certain time, determine the infection source. This problem is important in different contexts of computer or social networks. Assuming that the epidemic spread follows the usual susceptible-infected-recovered model, we introduce an inference algorithm based on dynamic message-passing equations and we show that it leads to significant improvement of performance compared to existing approaches. Importantly, this algorithm remains efficient in the case where the snapshot sees only a part of the network. PMID- 25122335 TI - Determination of effective brain connectivity from functional connectivity with application to resting state connectivities. AB - Neural field theory insights are used to derive effective brain connectivity matrices from the functional connectivity matrix defined by activity covariances. The symmetric case is exactly solved for a resting state system driven by white noise, in which strengths of connections, often termed effective connectivities, are inferred from functional data; these include strengths of connections that are underestimated or not detected by anatomical imaging. Proximity to criticality is calculated and found to be consistent with estimates obtainable from other methods. Links between anatomical, effective, and functional connectivity and resting state activity are quantified, with applicability to other complex networks. Proof-of-principle results are illustrated using published experimental data on anatomical connectivity and resting state functional connectivity. In particular, it is shown that functional connection matrices can be used to uncover the existence and strength of connections that are missed from anatomical connection matrices, including interhemispheric connections that are difficult to track with techniques such as diffusion spectrum imaging. PMID- 25122337 TI - Voter model on the two-clique graph. AB - I examine the mean consensus time (i.e., exit time) of the voter model in the so called two-clique graph. The two-clique graph is composed of two cliques interconnected by some links and considered as a toy model of networks with community structure or multilayer networks. I analytically show that, as the number of interclique links per node is varied, the mean consensus time experiences a crossover between a fast consensus regime [i.e., O(N)] and a slow consensus regime [i.e., O(N(2))], where N is the number of nodes. The fast regime is consistent with the result for homogeneous well-mixed graphs such as the complete graph. The slow regime appears only when the entire network has O(1) interclique links. The present results suggest that the effect of community structure on the consensus time of the voter model is fairly limited. PMID- 25122338 TI - Simultaneous first- and second-order percolation transitions in interdependent networks. AB - In a system of interdependent networks, an initial failure of nodes invokes a cascade of iterative failures that may lead to a total collapse of the whole system in the form of an abrupt first-order transition. When the fraction of initial failed nodes 1-p reaches criticality p = p(c), the abrupt collapse occurs by spontaneous cascading failures. At this stage, the giant component decreases slowly in a plateau form and the number of iterations in the cascade tau diverges. The origin of this plateau and its increasing with the size of the system have been unclear. Here we find that, simultaneously with the abrupt first order transition, a spontaneous second-order percolation occurs during the cascade of iterative failures. This sheds light on the origin of the plateau and how its length scales with the size of the system. Understanding the critical nature of the dynamical process of cascading failures may be useful for designing strategies for preventing and mitigating catastrophic collapses. PMID- 25122339 TI - Geometrical invariability of transformation between a time series and a complex network. AB - We present a dynamically equivalent transformation between time series and complex networks based on coarse geometry theory. In terms of quasi-isometric maps, we characterize how the underlying geometrical characters of complex systems are preserved during transformations. Fractal dimensions are shown to be the same for time series (or complex network) and its transformed counterpart. Results from the Rossler system, fractional Brownian motion, synthetic networks, and real networks support our findings. This work gives theoretical evidences for an equivalent transformation between time series and networks. PMID- 25122341 TI - Detecting network communities beyond assortativity-related attributes. AB - In network science, assortativity refers to the tendency of links to exist between nodes with similar attributes. In social networks, for example, links tend to exist between individuals of similar age, nationality, location, race, income, educational level, religious belief, and language. Thus, various attributes jointly affect the network topology. An interesting problem is to detect community structure beyond some specific assortativity-related attributes rho, i.e., to take out the effect of rho on network topology and reveal the hidden community structures which are due to other attributes. An approach to this problem is to redefine the null model of the modularity measure, so as to simulate the effect of rho on network topology. However, a challenge is that we do not know to what extent the network topology is affected by rho and by other attributes. In this paper, we propose a distance modularity, which allows us to freely choose any suitable function to simulate the effect of rho. Such freedom can help us probe the effect of rho and detect the hidden communities which are due to other attributes. We test the effectiveness of distance modularity on synthetic benchmarks and two real-world networks. PMID- 25122340 TI - Efficiently inferring community structure in bipartite networks. AB - Bipartite networks are a common type of network data in which there are two types of vertices, and only vertices of different types can be connected. While bipartite networks exhibit community structure like their unipartite counterparts, existing approaches to bipartite community detection have drawbacks, including implicit parameter choices, loss of information through one mode projections, and lack of interpretability. Here we solve the community detection problem for bipartite networks by formulating a bipartite stochastic block model, which explicitly includes vertex type information and may be trivially extended to k-partite networks. This bipartite stochastic block model yields a projection-free and statistically principled method for community detection that makes clear assumptions and parameter choices and yields interpretable results. We demonstrate this model's ability to efficiently and accurately find community structure in synthetic bipartite networks with known structure and in real-world bipartite networks with unknown structure, and we characterize its performance in practical contexts. PMID- 25122342 TI - Suppressing epidemics on networks by exploiting observer nodes. AB - To control infection spreading on networks, we investigate the effect of observer nodes that recognize infection in a neighboring node and make the rest of the neighbor nodes immune. We numerically show that random placement of observer nodes works better on networks with clustering than on locally treelike networks, implying that our model is promising for realistic social networks. The efficiency of several heuristic schemes for observer placement is also examined for synthetic and empirical networks. In parallel with numerical simulations of epidemic dynamics, we also show that the effect of observer placement can be assessed by the size of the largest connected component of networks remaining after removing observer nodes and links between their neighboring nodes. PMID- 25122343 TI - Competing spreading processes on multiplex networks: awareness and epidemics. AB - Epidemiclike spreading processes on top of multilayered interconnected complex networks reveal a rich phase diagram of intertwined competition effects. A recent study by the authors [C. Granell et al., Phys. Rev. Lett. 111, 128701 (2013).] presented an analysis of the interrelation between two processes accounting for the spreading of an epidemic, and the spreading of information awareness to prevent infection, on top of multiplex networks. The results in the case in which awareness implies total immunization to the disease revealed the existence of a metacritical point at which the critical onset of the epidemics starts, depending on completion of the awareness process. Here we present a full analysis of these critical properties in the more general scenario where the awareness spreading does not imply total immunization, and where infection does not imply immediate awareness of it. We find the critical relation between the two competing processes for a wide spectrum of parameters representing the interaction between them. We also analyze the consequences of a massive broadcast of awareness (mass media) on the final outcome of the epidemic incidence. Importantly enough, the mass media make the metacritical point disappear. The results reveal that the main finding, i.e., existence of a metacritical point, is rooted in the competition principle and holds for a large set of scenarios. PMID- 25122344 TI - Robustness of a network formed of spatially embedded networks. AB - We present analytic and numeric results for percolation in a network formed of interdependent spatially embedded networks. We show results for a treelike and a random regular network of networks each with (i) unconstrained dependency links and (ii) dependency links restricted to a maximum Euclidean length r. Analytic results are given for each network of networks with spatially unconstrained dependency links and compared to simulations. For the case of two fully interdependent spatially embedded networks it was found [Li et al., Phys. Rev. Lett. 108, 228702 (2012)] that the system undergoes a first-order phase transition only for r>r(c) ~ 8. We find here that for treelike networks of networks (composed of n networks) r(c) significantly decreases as n increases and rapidly (n >= 11) reaches its limiting value of 1. For cases where the dependencies form loops, such as in random regular networks, we show analytically and confirm through simulations that there is a certain fraction of dependent nodes, q(max), above which the entire network structure collapses even if a single node is removed. The value of q(max) decreases quickly with m, the degree of the random regular network of networks. Our results show the extreme sensitivity of coupled spatial networks and emphasize the susceptibility of these networks to sudden collapse. The theory proposed here requires only numerical knowledge about the percolation behavior of a single network and therefore can be used to find the robustness of any network of networks where the profile of percolation of a singe network is known numerically. PMID- 25122345 TI - Epidemic outbreaks in two-scale community networks. AB - We consider a model for the diffusion of epidemics in a population that is partitioned into local communities. In particular, assuming a mean-field approximation, we analyze a continuous-time susceptible-infected-susceptible (SIS) model that has appeared recently in the literature. The probability by which an individual infects individuals in its own community is different from the probability of infecting individuals in other communities. The aim of the model, compared to the standard, nonclustered one, is to provide a compact description for the presence of communities of local infection where the epidemic process is faster compared to the rate at which it spreads across communities. Ultimately, it provides a tool to express the probability of epidemic outbreaks in the form of a metastable infection probability. In the proposed model, the spatial structure of the network is encoded by the adjacency matrix of clusters, i.e., the connections between local communities, and by the vector of the sizes of local communities. Thus, the existence of a nontrivial metastable occupancy probability is determined by an epidemic threshold which depends on the clusters' size and on the intercommunity network structure. PMID- 25122346 TI - General optimization technique for high-quality community detection in complex networks. AB - Recent years have witnessed the development of a large body of algorithms for community detection in complex networks. Most of them are based upon the optimization of objective functions, among which modularity is the most common, though a number of alternatives have been suggested in the scientific literature. We present here an effective general search strategy for the optimization of various objective functions for community detection purposes. When applied to modularity, on both real-world and synthetic networks, our search strategy substantially outperforms the best existing algorithms in terms of final scores of the objective function. In terms of execution time for modularity optimization this approach also outperforms most of the alternatives present in literature with the exception of fastest but usually less efficient greedy algorithms. The networks of up to 30000 nodes can be analyzed in time spans ranging from minutes to a few hours on average workstations, making our approach readily applicable to tasks not limited by strict time constraints but requiring the quality of partitioning to be as high as possible. Some examples are presented in order to demonstrate how this quality could be affected by even relatively small changes in the modularity score stressing the importance of optimization accuracy. PMID- 25122348 TI - Effect of environment fluctuations on pattern formation of single species. AB - System-environment interactions are intrinsically nonlinear and dependent on the interplay between many degrees of freedom. The complexity may be even more pronounced when one aims to describe biologically motivated systems. In that case, it is useful to resort to simplified models relying on effective stochastic equations. A natural consideration is to assume that there is a noisy contribution from the environment, such that the parameters that characterize it are not constant but instead fluctuate around their characteristic values. From this perspective, we propose a stochastic generalization of the nonlocal Fisher KPP equation where, as a first step, environmental fluctuations are Gaussian white noises, both in space and time. We apply analytical and numerical techniques to study how noise affects stability and pattern formation in this context. Particularly, we investigate noise-induced coherence by means of the complementary information provided by the dispersion relation and the structure function. PMID- 25122347 TI - Interplay of network dynamics and heterogeneity of ties on spreading dynamics. AB - The structure of a network dramatically affects the spreading phenomena unfolding upon it. The contact distribution of the nodes has long been recognized as the key ingredient in influencing the outbreak events. However, limited knowledge is currently available on the role of the weight of the edges on the persistence of a pathogen. At the same time, recent works showed a strong influence of temporal network dynamics on disease spreading. In this work we provide an analytical understanding, corroborated by numerical simulations, about the conditions for infected stable state in weighted networks. In particular, we reveal the role of heterogeneity of edge weights and of the dynamic assignment of weights on the ties in the network in driving the spread of the epidemic. In this context we show that when weights are dynamically assigned to ties in the network, a heterogeneous distribution is able to hamper the diffusion of the disease, contrary to what happens when weights are fixed in time. PMID- 25122349 TI - Parallel discrete-event simulation schemes with heterogeneous processing elements. AB - To understand the effects of nonidentical processing elements (PEs) on parallel discrete-event simulation (PDES) schemes, two stochastic growth models, the restricted solid-on-solid (RSOS) model and the Family model, are investigated by simulations. The RSOS model is the model for the PDES scheme governed by the Kardar-Parisi-Zhang equation (KPZ scheme). The Family model is the model for the scheme governed by the Edwards-Wilkinson equation (EW scheme). Two kinds of distributions for nonidentical PEs are considered. In the first kind computing capacities of PEs are not much different, whereas in the second kind the capacities are extremely widespread. The KPZ scheme on the complex networks shows the synchronizability and scalability regardless of the kinds of PEs. The EW scheme never shows the synchronizability for the random configuration of PEs of the first kind. However, by regularizing the arrangement of PEs of the first kind, the EW scheme is made to show the synchronizability. In contrast, EW scheme never shows the synchronizability for any configuration of PEs of the second kind. PMID- 25122350 TI - Percolation on fitness-dependent networks with heterogeneous resilience. AB - The ability to understand the impact of adversarial processes on networks is crucial to various disciplines. The objects of study in this article are fitness driven networks. Fitness-dependent networks are fully described by a probability distribution of fitness and an attachment kernel. Every node in the network is endowed with a fitness value and the attachment kernel translates the fitness of two nodes into the probability that these two nodes share an edge. This concept is also known as mutual attractiveness. In the present article, fitness does not only serve as a measure of attractiveness, but also as a measure of a node's robustness against failure. The probability that a node fails increases with the number of failures in its direct neighborhood and decreases with higher fitness. Both static and dynamic network models are considered. Analytical results for the percolation threshold and the occupied fraction are derived. One of the results is that the distinction between the dynamic and the static model has a profound impact on the way failures spread over the network. Additionally, we find that the introduction of mutual attractiveness stabilizes the network compared to a pure random attachment. PMID- 25122351 TI - Networks maximizing the consensus time of voter models. AB - We explore the networks that yield the largest mean consensus time of voter models under different update rules. By analytical and numerical means, we show that the so-called lollipop graph, barbell graph, and double-star graph maximize the mean consensus time under the update rules called the link dynamics, voter model, and invasion process, respectively. For each update rule, the largest mean consensus time scales as O(N^{3}), where N is the number of nodes in the network. PMID- 25122352 TI - Hidden scaling patterns and universality in written communication. AB - The temporal statistics exhibited by written correspondence appear to be media dependent, with features which have so far proven difficult to characterize. We explain the origin of these difficulties by disentangling the role of spontaneous activity from decision-based prioritizing processes in human dynamics, clocking all waiting times through each agent's "proper time" measured by activity. This unveils the same fundamental patterns in written communication across all media (letters, email, sms), with response times displaying truncated power-law behavior and average exponents near -3/2. When standard time is used, the response time probabilities are theoretically predicted to exhibit a bimodal character, which is empirically borne out by our newly collected years-long data on email. These perspectives on the temporal dynamics of human correspondence should aid in the analysis of interaction phenomena in general, including resource management, optimal pricing and routing, information sharing, and emergency handling. PMID- 25122353 TI - Transmission of linear regression patterns between time series: from relationship in time series to complex networks. AB - The linear regression parameters between two time series can be different under different lengths of observation period. If we study the whole period by the sliding window of a short period, the change of the linear regression parameters is a process of dynamic transmission over time. We tackle fundamental research that presents a simple and efficient computational scheme: a linear regression patterns transmission algorithm, which transforms linear regression patterns into directed and weighted networks. The linear regression patterns (nodes) are defined by the combination of intervals of the linear regression parameters and the results of the significance testing under different sizes of the sliding window. The transmissions between adjacent patterns are defined as edges, and the weights of the edges are the frequency of the transmissions. The major patterns, the distance, and the medium in the process of the transmission can be captured. The statistical results of weighted out-degree and betweenness centrality are mapped on timelines, which shows the features of the distribution of the results. Many measurements in different areas that involve two related time series variables could take advantage of this algorithm to characterize the dynamic relationships between the time series from a new perspective. PMID- 25122354 TI - Modular networks with delayed coupling: synchronization and frequency control. AB - We study the collective dynamics of modular networks consisting of map-based neurons which generate irregular spike sequences. Three types of intramodule topology are considered: a random Erdos-Renyi network, a small-world Watts Strogatz network, and a scale-free Barabasi-Albert network. The interaction between the neurons of different modules is organized by relatively sparse connections with time delay. For all the types of the network topology considered, we found that with increasing delay two regimes of module synchronization alternate with each other: inphase and antiphase. At the same time, the average rate of collective oscillations decreases within each of the time-delay intervals corresponding to a particular synchronization regime. A dual role of the time delay is thus established: controlling a synchronization mode and degree and controlling an average network frequency. Furthermore, we investigate the influence on the modular synchronization by other parameters: the strength of intermodule coupling and the individual firing rate. PMID- 25122355 TI - Solutions of the higher-order Manakov-type continuous and discrete equations. AB - We derive exact and approximate localized solutions for the Manakov-type continuous and discrete equations. We establish the correspondence between the solutions of the coupled Ablowitz-Ladik equations and the solutions of the coupled higher-order Manakov equations. PMID- 25122356 TI - Dynamics in the Sakaguchi-Kuramoto model with two subpopulations [corrected]. AB - The dynamics in a variant of globally coupled Sakaguchi-Kuramoto [corrected]. phase oscillators is studied. The model consists of two subpopulations, each with a different phase lag and interaction strength. Using Ott-Antonson ansatz, we analyze the dynamics in the model and present the numerical results. There exist stationary synchronous states which are generalized pi states and two types of traveling wave states. We find that the traveling wave states are the dominant dynamics in comparison with the stationary states. Particularly, we find that the stationary and traveling wave states can be smoothly connected through the properly chosen parameter paths. PMID- 25122357 TI - Size-dependent diffusion promotes the emergence of spatiotemporal patterns. AB - Spatiotemporal patterns, indicating the spatiotemporal variability of individual abundance, are a pronounced scenario in ecological interactions. Most of the existing models for spatiotemporal patterns treat species as homogeneous groups of individuals with average characteristics by ignoring intraspecific physiological variations at the individual level. Here we explore the impacts of size variation within species resulting from individual ontogeny, on the emergence of spatiotemporal patterns in a fully size-structured population model. We found that size dependency of animal's diffusivity greatly promotes the formation of spatiotemporal patterns, by creating regular spatiotemporal patterns out of temporal chaos. We also found that size-dependent diffusion can substitute large-amplitude base harmonics with spatiotemporal patterns with lower amplitude oscillations but with enriched harmonics. Finally, we found that the single generation cycle is more likely to drive spatiotemporal patterns compared to predator-prey cycles, meaning that the mechanism of Hopf bifurcation might be more common than hitherto appreciated since the former cycle is more widespread than the latter in case of interacting populations. Due to the ubiquity of individual ontogeny in natural ecosystems we conclude that diffusion variability within populations is a significant driving force for the emergence of spatiotemporal patterns. Our results offer a perspective on self-organized phenomena, and pave a way to understand such phenomena in systems organized as complex ecological networks. PMID- 25122358 TI - Front propagation in a chaotic flow field. AB - We investigate numerically the dynamics of a propagating front in the presence of a spatiotemporally chaotic flow field. The flow field is the three-dimensional time-dependent state of spiral defect chaos generated by Rayleigh-Benard convection in a spatially extended domain. Using large-scale parallel numerical simulations, we simultaneously solve the Boussinesq equations and a reaction advection-diffusion equation with a Fischer-Kolmogorov-Petrovskii-Piskunov reaction for the transport of the scalar species in a large-aspect-ratio cylindrical domain for experimentally accessible conditions. We explore the front dynamics and geometry in the low-Damkohler-number regime, where the effect of the flow field is significant. Our results show that the chaotic flow field enhances the front propagation when compared with a purely cellular flow field. We quantify this enhancement by computing the spreading rate of the reaction products for a range of parameters. We use our results to quantify the complexity of the three-dimensional front geometry for a range of chaotic flow conditions. PMID- 25122359 TI - Dynamics of impurities in a three-dimensional volume-preserving map. AB - We study the dynamics of inertial particles in three-dimensional incompressible maps, as representations of volume-preserving flows. The impurity dynamics has been modeled, in the Lagrangian framework, by a six-dimensional dissipative bailout embedding map. The fluid-parcel dynamics of the base map is embedded in the particle dynamics governed by the map. The base map considered for the present study is the Arnold-Beltrami-Childress (ABC) map. We consider the behavior of the system both in the aerosol regime, where the density of the particle is larger than that of the base flow, as well as the bubble regime, where the particle density is less than that of the base flow. The phase spaces in both the regimes show rich and complex dynamics with three types of dynamical behaviors--chaotic structures, regular orbits, and hyperchaotic regions. In the one-action case, the aerosol regime is found to have periodic attractors for certain values of the dissipation and inertia parameters. For the aerosol regime of the two-action ABC map, an attractor merging and widening crisis is identified using the bifurcation diagram and the spectrum of Lyapunov exponents. After the crisis an attractor with two parts is seen, and trajectories hop between these parts with period 2. The bubble regime of the embedded map shows strong hyperchaotic regions as well as crisis induced intermittency with characteristic times between bursts that scale as a power law behavior as a function of the dissipation parameter. Furthermore, we observe a riddled basin of attraction and unstable dimension variability in the phase space in the bubble regime. The bubble regime in the one-action case shows similar behavior. This study of a simple model of impurity dynamics may shed light upon the transport properties of passive scalars in three-dimensional flows. We also compare our results with those seen earlier in two-dimensional flows. PMID- 25122360 TI - Shallow-water soliton dynamics beyond the Korteweg-de Vries equation. AB - An alternative way for the derivation of the new Korteweg-de Vries (KdV)-type equation is presented. The equation contains terms depending on the bottom topography (there are six new terms in all, three of which are caused by the unevenness of the bottom). It is obtained in the second-order perturbative approach in the weakly nonlinear, dispersive, and long wavelength limit. Only treating all these terms in the second-order perturbation theory made the derivation of this KdV-type equation possible. The motion of a wave, which starts as a KdV soliton, is studied according to the new equation in several cases by numerical simulations. The quantitative changes of a soliton's velocity and amplitude appear to be directly related to bottom variations. Changes of the soliton's velocity appear to be almost linearly anticorrelated with changes of water depth, whereas correlation of variation of soliton's amplitude with changes of water depth looks less linear. When the bottom is flat, the new terms narrow down the family of exact solutions, but at least one single soliton survives. This is also checked by numerics. PMID- 25122361 TI - Symbolic dynamics-based error analysis on chaos synchronization via noisy channels. AB - In this study, symbolic dynamics is used to research the error of chaos synchronization via noisy channels. The theory of symbolic dynamics reduces chaos to a shift map that acts on a discrete set of symbols, each of which contains information about the system state. Using this transformation, a coder-decoder scheme is proposed. A model for the relationship among word length, region number of a partition, and synchronization error is provided. According to the model, the fundamental trade-off between word length and region number can be optimized to minimize the synchronization error. Numerical simulations provide support for our results. PMID- 25122362 TI - Control for a synchronization-desynchronization switch. AB - How to freely enhance or suppress synchronization of networked dynamical systems is of great importance in many disciplines. A unified precise control method for a synchronization-desynchronization switch, called the pull-push control method, is suggested. Namely, synchronization can be achieved when the original systems are desynchronous by pulling (or protecting) one node or a certain subset of nodes, whereas desynchronization can be accomplished when the systems are already synchronous by pushing (or kicking) one node or a certain subset of nodes. With this method, the controlled nodes should be chosen by the generalized eigenvector centrality of the critical synchronization mode of the Laplacian matrix. Compared with existing control methods for synchronization, it displays high efficiency, flexibility, and precision as well. PMID- 25122363 TI - Electrokinetic instability near charge-selective hydrophobic surfaces. AB - The influence of the texture of a hydrophobic surface on the electro-osmotic slip of the second kind and the electrokinetic instability near charge selective surfaces (permselective membranes, electrodes, or systems of microchannels and nanochannels) is investigated theoretically using a simple model based on the Rubinstein-Zaltzman approach. A simple formula is derived to evaluate the decrease in the instability threshold due to hydrophobicity. The study is complemented by numerical investigations both of linear and nonlinear instabilities near a hydrophobic membrane surface. Theory predicts a significant enhancement of the ion flux to the surface and shows a good qualitative agreement with the available experimental data. PMID- 25122364 TI - Chaotic motion of light particles in an unsteady three-dimensional vortex: experiments and simulation. AB - We study the chaotic motion of a small rigid sphere, lighter than the fluid in a three-dimensional vortex of finite height. Based on the results of Eulerian and Lagrangian measurements, a sequence of models is set up. The time-independent model is a generalization of the Burgers vortex. In this case, there are two types of attractors for the particle: a fixed point on the vortex axis and a limit cycle around the vortex axis. Time dependence might combine these regular attractors into a single chaotic attractor, however its robustness is much weaker than what the experiments suggest. To construct an aperiodically time-dependent advection dynamics in a simple way, Gaussian noise is added to the particle velocity in the numerical simulation. With an appropriate choice of the noise properties, mimicking the effect of local turbulence, a reasonable agreement with the experimentally observed particle statistics is found. PMID- 25122365 TI - Interfacial dynamics of two immiscible fluids in spatially periodic porous media: the role of substrate wettability. AB - We delineate the contact line dynamics of two immiscible fluids in a medium having spatially periodic porous structures. The flow is driven by an external applied pressure gradient. We bring out the combined consequences of the solid fraction distribution and the substrate wettability on the resulting dynamics of the contact line, by employing phase-field formalism. We capture the sequence of spatiotemporal events leading to formation of liquid bridges by trapping a small amount of displaced phase fluid between two consecutive porous blocks, as dictated by the combinations of substrate wettability and solid fraction. We also demonstrate the existence of a regime of complete interfacial recovery, depending on the parametric space of the governing parameters under concern. Our results essentially demonstrate the intricate mechanisms by virtue of which the wettabilities of the substrates alter the dynamical evolutions of interfaces and the subsequent shapes and sizes of the adsorbed dispersed phases, bearing far ranging consequences in several practical applications ranging from oil recovery to groundwater flow. PMID- 25122366 TI - Magnetic energy dissipation and mean magnetic field generation in planar convection-driven dynamos. AB - A numerical study of dynamos in rotating convecting plane layers is presented which focuses on magnetic energies and dissipation rates and the generation of mean fields (where the mean is taken over horizontal planes). The scaling of the magnetic energy with the flux Rayleigh number is different from the scaling proposed in spherical shells, whereas the same dependence of the magnetic dissipation length on the magnetic Reynolds number is found for the two geometries. Dynamos both with and without mean field exist in rapidly rotating convecting plane layers. PMID- 25122367 TI - Nonaxisymmetric high-aspect-ratio ellipsoids under shear: lowest-order correction for finite aspect ratios. AB - We extend the classic study of the motion of small ellipsoidal particles under shear, focusing on simplifications obtained by considerations of the extreme aspect ratios typical of rheoscopic particles (e.g., Kalliroscope). Specifically, we study conditions under which the long-time behavior of scalene (i.e., triaxial or nonaxisymmetric) ellipsoids are well approximated by a model that is low order in the appropriate aspect ratios. After enumerating and describing the generic long-time motions of such particles in the lowest-order model, we investigate corrections induced by the physically appropriate lowest-order correction to the base model, with special attention to a periodic wobbling motion special to scalene ellipsoids. PMID- 25122368 TI - Finite time blow-up and breaking of solitary wind waves. AB - The evolution of surface water waves in finite depth under wind forcing is reduced to an antidissipative Korteweg-de Vries-Burgers equation. We exhibit its solitary wave solution. Antidissipation accelerates and increases the amplitude of the solitary wave and leads to blow-up and breaking. Blow-up occurs in finite time for infinitely large asymptotic space so it is a nonlinear, dispersive, and antidissipative equivalent of the linear instability which occurs for infinite time. Due to antidissipation two given arbitrary and adjacent planes of constant phases of the solitary wave acquire different velocities and accelerations inducing breaking. Soliton breaking occurs in finite space in a time prior to the blow-up. We show that the theoretical growth in amplitude and the time of breaking are both testable in an existing experimental facility. PMID- 25122369 TI - dc Step response of induced-charge electro-osmosis between parallel electrodes at large voltages. AB - Induced-charge electro-osmosis (ICEO) is important since it can be used for realizing high performance microfluidic devices. Here, we analyze the simplest problem of ion relaxation around a circular polarizable cylinder between parallel blocking electrodes in a closed cell by using a multiphysics coupled simulation technique. This technique is based on a combination of the finite-element method and finite-volume method for the Poisson-Nernst-Planck (PNP) equations having a flow term and the Stokes equation having an electric stress term. Through this analysis, we successfully demonstrate that on application of dc voltages, quadorapolar ICEO vortex flows grow during the charging time of the cylinder for both unbounded and bounded problems and decay during the charging time of the parallel electrodes only for the bounded problem using blocking electrodes. Further, by proposing a simple model that considers the two-dimensional (2D) PNP equations analytically, we successfully explain the step response time of the ICEO flow for the both unbounded and bounded problems. Furthermore, at low applied voltages, we find analytical formulations on steady diffused-ion problems and steady ICEO-flow problems and examine that our numerical results agree well with the analytical results. Moreover, by considering an ion-conserving condition with 2D Poisson-Boltzmann equations, we explain significant decrease of the maximum slip velocity at large applied voltages fairly well. We believe that our analysis will contribute greatly to the realistic designs of prospective high performance microfluidic devices. PMID- 25122370 TI - Cyclones and attractive streaming generated by acoustical vortices. AB - Acoustical and optical vortices have attracted great interest due to their ability to capture and manipulate particles with the use of radiation pressure. Here we show that acoustical vortices can also induce axial vortical flow reminiscent of cyclones, whose topology can be controlled by adjusting the properties of the acoustical beam. In confined geometry, the phase singularity enables generating "attractive streaming" with the flow directed toward the transducer. This opens perspectives for contactless vortical flow control. PMID- 25122371 TI - Nonequilibrium shock-heated nitrogen flows using a rovibrational state-to-state method. AB - A rovibrational collisional model is developed to study the internal energy excitation and dissociation processes behind a strong shock wave in a nitrogen flow. The reaction rate coefficients are obtained from the ab initio database of the NASA Ames Research Center. The master equation is coupled with a one dimensional flow solver to study the nonequilibrium phenomena encountered in the gas during a hyperbolic reentry into Earth's atmosphere. The analysis of the populations of the rovibrational levels demonstrates how rotational and vibrational relaxation proceed at the same rate. This contrasts with the common misconception that translational and rotational relaxation occur concurrently. A significant part of the relaxation process occurs in non-quasi-steady-state conditions. Exchange processes are found to have a significant impact on the relaxation of the gas, while predissociation has a negligible effect. The results obtained by means of the full rovibrational collisional model are used to assess the validity of reduced order models (vibrational collisional and multitemperature) which are based on the same kinetic database. It is found that thermalization and dissociation are drastically overestimated by the reduced order models. The reasons of the failure differ in the two cases. In the vibrational collisional model the overestimation of the dissociation is a consequence of the assumption of equilibrium between the rotational energy and the translational energy. The multitemperature model fails to predict the correct thermochemical relaxation due to the failure of the quasi-steady-state assumption, used to derive the phenomenological rate coefficient for dissociation. PMID- 25122372 TI - Hydrodynamic interaction of microswimmers near a wall. AB - The hydrodynamics of an archetypal low-Reynolds number swimmer, called "squirmer," near a wall has been numerically studied. For a single squirmer, depending on the swimming mechanism, three different modes are distinguished: (a) the squirmer escaping from the wall, (b) the squirmer swimming along the wall at a constant distance and orientation angle, and (c) the squirmer swimming near the wall in a periodic trajectory. The role of inertial effects on the near-wall motion of the squirmer is quantified. The dynamics of multiple squirmers swimming between two walls is found to be very different from a single squirmer. Near-wall accumulation of squirmers are observed. At a relatively small concentration c = 0.1, around 60-80% of the squirmers are accumulated near the walls and attraction of pushers and pullers toward the wall is stronger than neutral squirmers. Near wall squirmers orient normal to the wall, while in the bulk region, the squirmers are mostly oriented parallel to the wall. At a high concentration c = 0.4, the percentage of the near-wall squirmers is around 40%. The orientation angle of squirmers in the bulk region is more uniformly distributed at high concentrations. In the near-wall region, pullers repel each other, while pushers are attracted to each other and form clusters. PMID- 25122373 TI - Spanwise gradients in flow speed help stabilize leading-edge vortices on revolving wings. AB - While a leading-edge vortex on an infinite translating wing is shed after a short distance of travel, its counterpart on a finite span revolving insect wing or maple seed membrane exhibits robust attachment. The latter explains the aerodynamic lift generated by such biological species. Here we analyze the mechanisms responsible for leading-edge vortex attachment. We compute the Navier Stokes solution of the flow past a finite span wing (i) embedded in a uniform oncoming flow, (ii) embedded in a spanwise varying oncoming flow, and (iii) revolving about its root. We show that over flapping amplitudes typical of insect flight (phi = 120 degrees ), the spanwise gradient of the local wing speed may suffice in maintaining leading-edge vortex attachment. We correlate this result with the development of spanwise flow, driven by the spanwise gradient of pressure, and we evaluate the sensitivity of such a mechanism to the Reynolds number. It is noted, however, that leading-edge vortex attachment through the spanwise gradient of the local wing speed does not promote large lift, which ultimately arises from centrifugal and Coriolis effects. PMID- 25122374 TI - Simple model of a planar undulating magnetic microswimmer. AB - One of the most efficient actuation methods of robotic microswimmers for biomedical applications is by applying time-varying external magnetic fields. In order to improve the design of the swimmer and optimize its performance, one needs to develop simple theoretical models that enable explicit analysis of the swimmer's dynamics. This paper studies the dynamics of a simple microswimmer model with two magnetized links connected by an elastic joint, which undergoes planar undulations induced by an oscillating magnetic field. The nonlinear dynamics of the microswimmer is formulated by assuming Stokes flow and using resistive force theory to calculate the viscous drag forces. Key effects that enable the swimmer to overcome the scallop theorem and generate net propulsion are identified, including violation of front-back symmetry. Assuming small oscillation amplitude, approximate solution is derived by using perturbation expansion, and leading-order expressions for the swimmer's displacement per cycle X and average speed V are obtained. Optimal actuation frequencies that maximize X or V are found for given swimmer's parameters. An ultimate optimal choice of swimmer's parameters and actuation frequency is found, for which the average swimming speed V attains a global maximum. Finally, the theoretical predictions of optimal performance values are validated by comparison to reported experimental results of magnetic microswimmers. PMID- 25122375 TI - Interfacial pattern formation in confined power-law fluids. AB - The interfacial pattern formation problem in an injection-driven radial Hele-Shaw flow is studied for the situation in which a Newtonian fluid of negligible viscosity displaces a viscous non-Newtonian power-law fluid. By utilizing a Darcy law-like formulation, we tackle the fluid-fluid interface evolution problem perturbatively, and we derive second-order mode-coupling equations that describe the time evolution of the perturbation amplitudes. This allows us to investigate analytically how the non-Newtonian nature of the dislocated fluid determines the morphology of the emerging interfacial patterns. If the pushed fluid is shear thinning, our results indicate the development of side-branching structures. On the other hand, if the displaced fluid is shear-thickening, one detects the formation of petal-like shapes, markedly characterized by strong tip-splitting events. Finally, a time-dependent injection protocol is presented that is able to restrain finger proliferation via side-branching and tip-splitting. This permits the emergence of symmetric n-fold interfacial shapes for which the number of fingers remains fixed as time progresses. This procedure generalizes existing controlling strategies for purely Newtonian flow circumstances to the case of a non-Newtonian, displaced power-law fluid. PMID- 25122376 TI - Dynamics of the vapor layer below a Leidenfrost drop. AB - In the Leidenfrost effect a small drop of fluid is levitated, above a sufficiently hot surface, on a persistent vapor layer generated by evaporation from the drop. The vapor layer thermally insulates the drop from the surface leading to extraordinarily long drop lifetimes. The top-view shape of the levitated drops can exhibit persistent starlike vibrations. I extend recent work [Burton et al., Phys. Rev. Lett. 109, 074301 (2012)] to study the bottom surface of the drop using interference imaging. In this work I use a high-speed camera and automated image analysis to image, locate, and classify the interference fringes. From the interference fringes I reconstruct the shape and height profile of the rim where the drop is closest to the surface. I measure the drop-size dependence of the planar vibrational mode frequencies, which agree well with previous work. I observe a distinct breathing mode in the average radius of the drop, the frequency of which scales differently with drop size than the other modes. This breathing mode can be tightly coupled to a vertical motion of the drop. I further observe a qualitative difference in the structure and dynamics of the vertical profile of the rim between large and small drops. PMID- 25122377 TI - Dynamics of an axisymmetric liquid bridge close to the minimum-volume stability limit. AB - We analyze both theoretically and experimentally the dynamical behavior of an isothermal axisymmetric liquid bridge close to the minimum-volume stability limit. First, the nature of this stability limit is investigated experimentally by determining the liquid bridge response to a mass force pulse for volumes just above that limit. In our experiments, the liquid bridge breakup takes place only when the critical volume is surpassed and is never triggered by the mass force pulse. Second, the growth of the small-amplitude perturbation mode initiating the liquid bridge breakage is measured experimentally and calculated from the linearized Navier-Stokes equations. The results of the linear stability analysis allow one to explain why liquid bridges with volumes just above the stability limit are so robust. Finally, the nonlinear process leading to the liquid bridge breakup is described from both experimental data and the solution of the full Navier-Stokes equations. Special attention is paid to the free-surface pinchoff. The results show that the flow becomes universal (independent of both the initial and boundary conditions) sufficiently close to that singularity and suggest that the transition from the inviscid to the viscous regime is about to take place in the final stage of both the experiments and numerical simulations. PMID- 25122378 TI - Lattice model for spontaneous imbibition in porous media: the role of effective tension and universality class. AB - Recently, anomalous scaling properties of front broadening during spontaneous imbibition of water in Vycor glass, a nanoporous medium, were reported: the mean height and the width of the propagating front increase with time t both proportional to t(1/2). Here, we propose a simple lattice imbibition model and elucidate quantitatively how the correlation range of the hydrostatic pressure and the disorder strength of the pore radii affect the scaling properties of the imbibition front. We introduce an effective tension of liquid across neighboring pores, which depends on the aspect ratio of each pore, and show that it leads to a dynamical crossover: both the mean height and the roughness grow faster in the presence of tension in the intermediate-time regime but eventually saturate in the long-time regime. The universality class of the long-time behavior is discussed by examining the associated scaling exponents and their relation to directed percolation. PMID- 25122379 TI - Effect of velocity boundary conditions on the heat transfer and flow topology in two-dimensional Rayleigh-Benard convection. AB - The effect of various velocity boundary condition is studied in two-dimensional Rayleigh-Benard convection. Combinations of no-slip, stress-free, and periodic boundary conditions are used on both the sidewalls and the horizontal plates. For the studied Rayleigh numbers Ra between 10(8) and 10(11) the heat transport is lower for Gamma=0.33 than for Gamma=1 in case of no-slip sidewalls. This is, surprisingly, the opposite for stress-free sidewalls, where the heat transport increases for a lower aspect ratio. In wider cells the aspect-ratio dependence is observed to disappear for Ra >= 10(10). Two distinct flow types with very different dynamics can be seen, mostly dependent on the plate velocity boundary condition, namely roll-like flow and zonal flow, which have a substantial effect on the dynamics and heat transport in the system. The predominantly horizontal zonal flow suppresses heat flux and is observed for stress-free and asymmetric plates. Low aspect-ratio periodic sidewall simulations with a no-slip boundary condition on the plates also exhibit zonal flow. In all the other cases, the flow is roll like. In two-dimensional Rayleigh-Benard convection, the velocity boundary conditions thus have large implications on both roll-like and zonal flow that have to be taken into consideration before the boundary conditions are imposed. PMID- 25122380 TI - Statistics of the inverse-cascade regime in two-dimensional magnetohydrodynamic turbulence. AB - We present a detailed direct numerical simulation of statistically steady, homogeneous, isotropic, two-dimensional magnetohydrodynamic turbulence. Our study concentrates on the inverse cascade of the magnetic vector potential. We examine the dependence of the statistical properties of such turbulence on dissipation and friction coefficients. We extend earlier work significantly by calculating fluid and magnetic spectra, probability distribution functions (PDFs) of the velocity, magnetic, vorticity, current, stream-function, and magnetic-vector potential fields, and their increments. We quantify the deviations of these PDFs from Gaussian ones by computing their flatnesses and hyperflatnesses. We also present PDFs of the Okubo-Weiss parameter, which distinguishes between vortical and extensional flow regions, and its magnetic analog. We show that the hyperflatnesses of PDFs of the increments of the stream function and the magnetic vector potential exhibit significant scale dependence and we examine the implication of this for the multiscaling of structure functions. We compare our results with those of earlier studies. PMID- 25122381 TI - Casimir effect in active matter systems. AB - We numerically examine run-and-tumble active matter particles in Casimir geometries composed of two finite parallel walls. We find that there is an attractive force between the two walls of a magnitude that increases with increasing run length. The attraction exhibits an unusual exponential dependence on the wall separation, and it arises due to a depletion of swimmers in the region between the walls by a combination of the motion of the particles along the walls and a geometric shadowing effect. This attraction is robust as long as the wall length is comparable to or smaller than the swimmer run length, and is only slightly reduced by the inclusion of steric interactions between swimmers. We also examine other geometries and find regimes in which there is a crossover from attraction to repulsion between the walls as a function of wall separation and wall length. PMID- 25122382 TI - Motion transitions of falling plates via quasisteady aerodynamics. AB - In this paper, we study the dynamics of freely falling plates based on the Kirchhoff equation and the quasisteady aerodynamic model. Motion transitions among fluttering, tumbling along a cusp-like trajectory, irregular, and tumbling along a straight trajectory are obtained by solving the dynamical equations. Phase diagrams spanning between the nondimensional moment of inertia and aerodynamic coefficients or aspect ratio are built to identify regimes for these falling styles. We also investigate the stability of fixed points and bifurcation scenarios. It is found that the transitions are all heteroclinic bifurcations and the influence of the fixed-point stability is local. PMID- 25122383 TI - Diffuse-interface modeling of liquid-vapor coexistence in equilibrium drops using smoothed particle hydrodynamics. AB - We study numerically liquid-vapor phase separation in two-dimensional, nonisothermal, van der Waals (vdW) liquid drops using the method of smoothed particle hydrodynamics (SPH). In contrast to previous SPH simulations of drop formation, our approach is fully adaptive and follows the diffuse-interface model for a single-component fluid, where a reversible, capillary (Korteweg) force is added to the equations of motion to model the rapid but smooth transition of physical quantities through the interface separating the bulk phases. Surface tension arises naturally from the cohesive part of the vdW equation of state and the capillary forces. The drop models all start from a square-shaped liquid and spinodal decomposition is investigated for a range of initial densities and temperatures. The simulations predict the formation of stable, subcritical liquid drops with a vapor atmosphere, with the densities and temperatures of coexisting liquid and vapor in the vdW phase diagram closely matching the binodal curve. We find that the values of surface tension, as determined from the Young-Laplace equation, are in good agreement with the results of independent numerical simulations and experimental data. The models also predict the increase of the vapor pressure with temperature and the fitting to the numerical data reproduces very well the Clausius-Clapeyron relation, thus allowing for the calculation of the vaporization pressure for this vdW fluid. PMID- 25122384 TI - Statistical symmetries of the Lundgren-Monin-Novikov hierarchy. AB - It was shown by Oberlack and Rosteck [Discr. Cont. Dyn. Sys. S, 3, 451 2010] that the infinite set of multipoint correlation (MPC) equations of turbulence admits a considerable extended set of Lie point symmetries compared to the Galilean group, which is implied by the original set of equations of fluid mechanics. Specifically, a new scaling group and an infinite set of translational groups of all multipoint correlation tensors have been discovered. These new statistical groups have important consequences for our understanding of turbulent scaling laws as they are essential ingredients of, e.g., the logarithmic law of the wall and other scaling laws, which in turn are exact solutions of the MPC equations. In this paper we first show that the infinite set of translational groups of all multipoint correlation tensors corresponds to an infinite dimensional set of translations under which the Lundgren-Monin-Novikov (LMN) hierarchy of equations for the probability density functions (PDF) are left invariant. Second, we derive a symmetry for the LMN hierarchy which is analogous to the scaling group of the MPC equations. Most importantly, we show that this symmetry is a measure of the intermittency of the velocity signal and the transformed functions represent PDFs of an intermittent (i.e., turbulent or nonturbulent) flow. Interesting enough, the positivity of the PDF puts a constraint on the group parameters of both shape and intermittency symmetry, leading to two conclusions. First, the latter symmetries may no longer be Lie group as under certain conditions group properties are violated, but still they are symmetries of the LMN equations. Second, as the latter two symmetries in its MPC versions are ingredients of many scaling laws such as the log law, the above constraints implicitly put weak conditions on the scaling parameter such as von Karman constant kappa as they are functions of the group parameters. Finally, let us note that these kind of statistical symmetries are of much more general type, i.e., not limited to MPC or PDF equations emerging from Navier-Stokes, but instead they are admitted by other nonlinear partial differential equations like, for example, the Burgers equation when in conservative form and if the nonlinearity is quadratic. PMID- 25122385 TI - Humidity distribution affected by freely exposed water surfaces: simulations and experimental verification. AB - Accurate models for the water vapor flux at a water-air interface are required in various scientific, reliability and civil engineering aspects. Here, a study of humidity distribution in a container with air and freely exposed water is presented. A model predicting a spatial distribution and time evolution of relative humidity based on statistical rate theory and computational fluid dynamics is developed. In our approach we use short-term steady-state steps to simulate the slowly evolving evaporation in the system. Experiments demonstrate considerably good agreement with the computer modeling and allow one to distinguish the most important parameters for the model. PMID- 25122386 TI - Casimir effect in swimmer suspensions. AB - We show that the Casimir effect can emerge in microswimmer suspensions. In principle, two effects conspire against the development of Casimir effects in swimmer suspensions. First, at low Reynolds number, the force on any closed volume vanishes, but here the relevant effect is the drag by the flow produced by the swimmers, which can be finite. Second, the fluid velocity and the pressure are linear on the swimmer force dipoles, and averaging over the swimmer orientations would lead to a vanishing effect. However, being that the suspension is a discrete system, the noise terms of the coarse-grained equations depend on the density, which itself fluctuates, resulting in effective nonlinear dynamics. Applying the tools developed for other nonequilibrium systems to general coarse grained equations for swimmer suspensions, the Casimir drag is computed on immersed objects, and it is found to depend on the correlation function between the rescaled density and dipolar density fields. By introducing a model correlation function with medium-range order, explicit expressions are obtained for the Casimir drag on a body. When the correlation length is much larger than the microscopic cutoff, the average drag is independent of the correlation length, with a range that depends only on the size of the immersed bodies. PMID- 25122387 TI - Geometrical interpretation of long-time tails of first-passage time distributions in porous media with stagnant parts. AB - Using a combined experimental-numerical approach, we study the first-passage time distributions (FPTD) of small particles in two-dimensional porous materials. The distributions in low-porosity structures show persistent long-time tails, which are independent of the Peclet number and therefore cannot be explained by the advection-diffusion equation. Instead, our results suggest that these tails are caused by stagnant, i.e., quiescent areas where particles are trapped for some time. Comparison of measured FPTD with an analytical expression for the residence time of particles, which diffuse in confined regions and are able to escape through a small pore, yields good agreement with our data. PMID- 25122388 TI - Saturation of shape instabilities in single-bubble sonoluminescence. AB - Excitation of shape instabilities represents one route to bubble death in single bubble sonoluminescence. This feature is satisfactorily explained by an expansion to first order in the amplitude of a shape distortion in the form of a spherical harmonic. By taking the expansion to second order, it is found that regions of parameter space exist where the exponential growth into bubble disruption is checked and a saturated stable state of shape distortion is possible. Experimental evidence provided by Mie scattering is presented, and a possible connection to simultaneous spatially anisotropic light emission is discussed. PMID- 25122389 TI - Chaotic mixing in effective compressible flows. AB - We study numerically joint mixing of salt and colloids by chaotic advection and how salt inhomogeneities accelerate or delay colloid mixing by inducing a velocity drift V(dp) between colloids and fluid particles as proposed in recent experiments [J. Deseigne et al., Soft Matter 10, 4795 (2014)]. We demonstrate that because the drift velocity is no longer divergence free, small variations to the total velocity field drastically affect the evolution of colloid variance sigma(2) = -(2). A consequence is that mixing strongly depends on the mutual coherence between colloid and salt concentration fields, the short time evolution of scalar variance being governed by a new variance production term P = -/2 when scalar gradients are not developed yet so that dissipation is weak. Depending on initial conditions, mixing is then delayed or enhanced, and it is possible to find examples for which the two regimes (fast mixing followed by slow mixing) are observed consecutively when the variance source term reverses its sign. This is indeed the case for localized patches modeled as Gaussian concentration profiles. PMID- 25122390 TI - Extension of the dielectric breakdown model for simulation of viscous fingering at finite viscosity ratios. AB - Immiscible displacement of viscous oil by water in a petroleum reservoir is often hydrodynamically unstable. Due to similarities between the physics of dielectric breakdown and immiscible flow in porous media, we extend the existing dielectric breakdown model to simulate viscous fingering patterns for a wide range of viscosity ratios (MU(r)). At low values of power-law index eta, the system behaves like a stable Eden growth model and as the value of eta is increased to unity, diffusion limited aggregation-like fractals appear. This model is compared with our two-dimensional (2D) experiments to develop a correlation between the viscosity ratio and the power index, i.e., eta = 10(-5)MU(r)(0.8775). The 2D and three-dimensional (3D) simulation data appear scalable. The fingering pattern in 3D simulations at finite viscosity ratios appear qualitatively similar to the few experimental results published in the literature. PMID- 25122391 TI - Taylor column instability in the problem of a vibrational hydrodynamic top. AB - The object of experimental study is a fluid flow generated by differential rotation of a free light spherical body in a rotating cylindrical cavity. The body stays near the axis under the action of centrifugal force. The body rotation is generated by a force field oscillating in the cavity reference system (vibrational hydrodynamic top). It was found that the Taylor-Proudman column that forms undergoes instability, which manifests itself in the formation of a two dimensional azimuthal wave at the column boundary, in a Stewartson layer. The experimental results are summarized on a plane of dimensionless parameters, i.e., the dimensionless velocity of the cavity rotation and Rossby number. The bounds of the Stewartson layer stability were found and the supercritical structures and transition sequences were studied. Systematic research into that problem in its classical formulation--when a sphere is fixed on the axis and its differential rotation is imposed--was done for comparison. It was demonstrated that in conditions of vibratory differential rotation of a free sphere the stability threshold of the Stewartson layer was reduced by more than one order of magnitude, in comparison with the classical case. A qualitative change was also found in the wave phase velocity which for a free sphere exceeds the lagging differential rotation velocity of the body. It was concluded that the uncovered specifics are related to the difference in the mechanism of the Taylor-Proudman column formation and of the flow generation in it. For a vibrational hydrodynamic top, streams in the column will not be defined by Ekman pumping but by steady streaming, which is also responsible for the free-sphere differential rotation. PMID- 25122392 TI - Dynamics of a self-diffusiophoretic particle in shear flow. AB - Colloidal particles can achieve autonomous motion by a number of physicochemical mechanisms. For instance, if a spherical particle acts as a catalyst with an asymmetric surface reactivity, a molecular solute concentration gradient will develop in the surrounding fluid that can propel the particle via self diffusiophoresis. Theoretical analyses of self-diffusiophoresis have mostly been considered in quiescent fluid, where the solute concentration is usually assumed to evolve solely via diffusion. In practical applications, however, self propelled colloidal particles can be expected to reside in flowing fluids. Here, we examine the role of ambient flow on self-diffusiophoresis by quantifying the dynamics of a model Janus particle in a simple shear flow. The imposed flow can distort the self-generated solute concentration gradient. The extent of this distortion is quantified by a Peclet number, Pe, associated with the shear flow. Utilizing matched asymptotic analysis, we determine the concentration gradient surrounding a Janus particle in shear flow at a small, but finite, Peclet number and the resulting particle motion. For example, when the symmetry axis of the particle is aligned with the imposed flow, the Janus particle experiences an O(Pe) cross-streamline drift and an O(Pe(3/2)) reduction in translational velocity along the flow direction. We then analyze the in-plane trajectory of the Janus particle in shear. We find that the particle performs elliptical orbits around its initial position in the flow, which decrease in size with increasing Pe. PMID- 25122393 TI - Three-dimensional coherent structures of electrokinetic instability. AB - A direct numerical simulation of the three-dimensional elektrokinetic instability near a charge-selective surface (electric membrane, electrode, or system of micro or nanochannels) has been carried out and analyzed. A special finite-difference method has been used for the space discretization along with a semi-implicit 31/3 step Runge-Kutta scheme for the integration in time. The calculations employ parallel computing. Three characteristic patterns, which correspond to the overlimiting currents, are observed: (a) two-dimensional electroconvective rolls, (b) three-dimensional regular hexagonal structures, and (c) three-dimensional structures of spatiotemporal chaos, which are a combination of unsteady hexagons, quadrangles, and triangles. The transition from (b) to (c) is accompanied by the generation of interacting two-dimensional solitary pulses. PMID- 25122394 TI - Pore-scale simulation of fluid flow and solute dispersion in three-dimensional porous media. AB - In the present work fluid flow and solute transport through porous media are described by solving the governing equations at the pore scale with finite-volume discretization. Instead of solving the simplified Stokes equation (very often employed in this context) the full Navier-Stokes equation is used here. The realistic three-dimensional porous medium is created in this work by packing together, with standard ballistic physics, irregular and polydisperse objects. Emphasis is placed on numerical issues related to mesh generation and spatial discretization, which play an important role in determining the final accuracy of the finite-volume scheme and are often overlooked. The simulations performed are then analyzed in terms of velocity distributions and dispersion rates in a wider range of operating conditions, when compared with other works carried out by solving the Stokes equation. Results show that dispersion within the analyzed porous medium is adequately described by classical power laws obtained by analytic homogenization. Eventually the validity of Fickian diffusion to treat dispersion in porous media is also assessed. PMID- 25122395 TI - Asymptotic separation in multispecies collisional plasma shocks. AB - When a piston drives a shock in a multicomponent plasma, residual separation of the ion species persists close to the piston-plasma boundary, long after the shock has propagated away from the boundary and has reached a (nearly) steady state solution. This effect is observed in hybrid particle-in-cell simulations with two kinetic ion species and fluid electrons. It is a consequence of the different dynamics experienced by ions of different mass and charge-to-mass ratio and must be taken into account to properly model the physics of species separation in collisional plasma shocks. PMID- 25122396 TI - Experimental measurement of velocity correlations for two microparticles in a plasma with ion flow. AB - Velocity correlations are measured in a dusty plasma with only two microparticles. These correlations allow a characterization of the oscillatory modes and an identification of the effects of ion wakes. Ion wake effects are isolated by comparing two experiments with the microparticles aligned parallel vs perpendicular to the ion flow. From records of microparticle velocities, the one- and two-particle distribution functions f(1) and f(2) are obtained, and the two particle correlation function g(2) = f(2)-f(1)f(1) is calculated. Comparing the two experiments, we find that motion is much more correlated when the microparticles are aligned with the ion flow and the character of the oscillatory modes depends on the ion flow direction due to the ion wake. PMID- 25122397 TI - Quantum-relativistic hydrodynamic model for a spin-polarized electron gas interacting with light. AB - We develop a semirelativistic quantum fluid theory based on the expansion of the Dirac Hamiltonian to second order in 1/c. By making use of the Madelung representation of the wave function, we derive a set of hydrodynamic equations that comprises a continuity equation, an Euler equation for the mean velocity, and an evolution equation for the electron spin density. This hydrodynamic model is then applied to study the dynamics of a dense and weakly relativistic electron plasma. In particular, we investigate the impact of the quantum-relativistic spin effects on the Faraday rotation in a one-dimensional plasma slab irradiated by an x-ray laser source. PMID- 25122399 TI - Superdiffusion of two-dimensional Yukawa liquids due to a perpendicular magnetic field. AB - Stochastic transport of a two-dimensional (2D) dusty plasma liquid with a perpendicular magnetic field is studied. Superdiffusion is found to occur especially at higher magnetic fields with beta of order unity. Here, beta = omega(c)/omega(pd) is the ratio of the cyclotron and plasma frequencies for dust particles. The mean-square displacement MSD = 4D(alpha)t(alpha) is found to have an exponent alpha > 1, indicating superdiffusion, with alpha increasing monotonically to 1.1 as beta increases to unity. The 2D Langevin molecular dynamics simulation used here also reveals that another indicator of random particle motion, the velocity autocorrelation function, has a dominant peak frequency omega(peak) that empirically obeys omega(peak)(2) = omega(c)(2) + omega(pd)(2)/4. PMID- 25122401 TI - Interaction force in a vertical dust chain inside a glass box. AB - Small number dust particle clusters can be used as probes for plasma diagnostics. The number of dust particles as well as cluster size and shape can be easily controlled employing a glass box placed within a Gaseous Electronics Conference (GEC) rf reference chamber to provide confinement of the dust. The plasma parameters inside this box and within the larger plasma chamber have not yet been adequately defined. Adjusting the rf power alters the plasma conditions causing structural changes of the cluster. This effect can be used to probe the relationship between the rf power and other plasma parameters. This experiment employs the sloshing and breathing modes of small cluster oscillations to examine the relationship between system rf power and the particle charge and plasma screening length inside the glass box. The experimental results provided indicate that both the screening length and dust charge decrease as rf power inside the box increases. The decrease in dust charge as power increases may indicate that ion trapping plays a significant role in the sheath. PMID- 25122400 TI - Observation of self-excited acoustic vortices in defect-mediated dust acoustic wave turbulence. AB - Using the self-excited dust acoustic wave as a platform, we demonstrate experimental observation of self-excited fluctuating acoustic vortex pairs with +/- 1 topological charges through spontaneous waveform undulation in defect mediated turbulence for three-dimensional traveling nonlinear longitudinal waves. The acoustic vortex pair has helical waveforms with opposite chirality around the low-density hole filament pair in xyt space (the xy plane is the plane normal to the wave propagation direction). It is generated through ruptures of sequential crest surfaces and reconnections with their trailing ruptured crest surfaces. The initial rupture is originated from the amplitude reduction induced by the formation of the kinked wave crest strip with strong stretching through the undulation instability. Increasing rupture causes the separation of the acoustic vortex pair after generation. A similar reverse process is followed for the acoustic vortex annihilating with the opposite-charged acoustic vortex from the same or another pair generation. PMID- 25122402 TI - Role of viscous friction in the reverse rotation of a disk. AB - The mechanical response of a circularly driven disk in a dissipative medium is considered. We focus on the role played by viscous friction in the spinning motion of the disk, especially on the effect called reverse rotation, where the intrinsic and orbital rotations are antiparallel. Contrary to what happens in the frictionless case, where steady reverse rotations are possible, we find that this dynamical behavior may exist only as a transient when dissipation is considered. Whether or not reverse rotations in fact occur depends on the initial conditions and on two parameters, one related to dragging, inertia, and driving, the other associated with the geometric configuration of the system. The critical value of this geometric parameter (separating the regions where reverse rotation is possible from those where it is forbidden) as a function of viscosity is well adjusted by a q-exponential function. PMID- 25122398 TI - Equilibration dynamics and conductivity of warm dense hydrogen. AB - We investigate subpicosecond dynamics of warm dense hydrogen at the XUV free electron laser facility (FLASH) at DESY (Hamburg). Ultrafast impulsive electron heating is initiated by a <= 300-fs short x-ray burst of 92-eV photon energy. A second pulse probes the sample via x-ray scattering at jitter-free variable time delay. We show that the initial molecular structure dissociates within (0.9 +/- 0.2) ps, allowing us to infer the energy transfer rate between electrons and ions. We evaluate Saha and Thomas-Fermi ionization models in radiation hydrodynamics simulations, predicting plasma parameters that are subsequently used to calculate the static structure factor. A conductivity model for partially ionized plasma is validated by two-temperature density-functional theory coupled to molecular dynamic simulations and agrees with the experimental data. Our results provide important insights and the needed experimental data on transport properties of dense plasmas. PMID- 25122403 TI - Self-similar propagation and asymptotic optical waves in nonlinear waveguides. AB - The properties of self-similar optical waves propagating in a tapered cubic quintic nonlinear waveguide are investigated. Using a lens-type transformation we obtain the exact analytical self-similar solutions which describe the propagation of bright-shaped solitons, dark-shaped solitons, kink-shaped solitons, and antikink-shaped solitons. The stability of the solutions is examined by numerical simulations such that stable bright solitons are found. Beyond the exact analytical solutions, asymptotic optical waves are also found by employing a direct ansatz. These waves possess linear chirps and can propagate self similarly. The possibility of controlling the shape of output asymptotic optical waves is demonstrated. The analytical results are confirmed by numerical simulations. Finally, we investigate the generation and propagation properties of self-similar optical waves in a quintic nonlinear medium. PMID- 25122404 TI - Improved transfer matrix methods for calculating quantum transmission coefficient. AB - Methods for calculating the transmission coefficient are proposed, all of which arise from improved nonreflecting WKB boundary conditions at the edge of the computational domain in one-dimensional geometries. In the first, the Schrodinger equation is solved numerically, while the second is a transfer matrix (TM) algorithm where the potential is approximated by steps, but with the first and last matrix modified to reflect the new boundary condition. Both methods give excellent results with first-order WKB boundary conditions. The third uses the transfer matrix method with third-order WKB boundary conditions. For the parabolic potential, the average error for the modified third-order TM method reduces by factor of 4100 over the unmodified TM method. PMID- 25122405 TI - Theory of ion transport with fast acid-base equilibrations in bioelectrochemical systems. AB - Bioelectrochemical systems recover valuable components and energy in the form of hydrogen or electricity from aqueous organic streams. We derive a one-dimensional steady-state model for ion transport in a bioelectrochemical system, with the ions subject to diffusional and electrical forces. Since most of the ionic species can undergo acid-base reactions, ion transport is combined in our model with infinitely fast ion acid-base equilibrations. The model describes the current-induced ammonia evaporation and recovery at the cathode side of a bioelectrochemical system that runs on an organic stream containing ammonium ions. We identify that the rate of ammonia evaporation depends not only on the current but also on the flow rate of gas in the cathode chamber, the diffusion of ammonia from the cathode back into the anode chamber, through the ion exchange membrane placed in between, and the membrane charge density. PMID- 25122406 TI - Boundary condition at a two-phase interface in the lattice Boltzmann method for the convection-diffusion equation. AB - A boundary scheme in the lattice Boltzmann method (LBM) for the convection diffusion equation, which correctly realizes the internal boundary condition at the interface between two phases with different transport properties, is presented. The difficulty in satisfying the continuity of flux at the interface in a transient analysis, which is inherent in the conventional LBM, is overcome by modifying the collision operator and the streaming process of the LBM. An asymptotic analysis of the scheme is carried out in order to clarify the role played by the adjustable parameters involved in the scheme. As a result, the internal boundary condition is shown to be satisfied with second-order accuracy with respect to the lattice interval, if we assign appropriate values to the adjustable parameters. In addition, two specific problems are numerically analyzed, and comparison with the analytical solutions of the problems numerically validates the proposed scheme. PMID- 25122407 TI - Multiscale dynamics of semiflexible polymers from a universal coarse-graining procedure. AB - Simulating the dynamics of a semiflexible polymer across time and length scales that bridge the rigid and flexible regimes requires a physically sound method for generating coarse-grained representations of the polymer. Here, we study the dynamic behavior of the discrete stretchable, shearable wormlike chain model, which can be used to coarse-grain a continuous semi-elastic chain at an arbitrary discretization. We show that the dynamics of this universal model match those of the wormlike chain at length scales above the discretization length. The evolution of the stress correlation, as probed through Brownian dynamics simulations, is found to reproduce the predicted behavior in both the rigid and flexible regimes, spanning over six orders of magnitude in time scales. The coarse-graining approach employed here thus enables dynamic simulation of semiflexible polymers at lengths and times that were previously inaccessible with conventional methods. PMID- 25122408 TI - Nonequilibrium scheme for computing the flux of the convection-diffusion equation in the framework of the lattice Boltzmann method. AB - In this paper, we propose a local nonequilibrium scheme for computing the flux of the convection-diffusion equation with a source term in the framework of the multiple-relaxation-time (MRT) lattice Boltzmann method (LBM). Both the Chapman Enskog analysis and the numerical results show that, at the diffusive scaling, the present nonequilibrium scheme has a second-order convergence rate in space. A comparison between the nonequilibrium scheme and the conventional second-order central-difference scheme indicates that, although both schemes have a second order convergence rate in space, the present nonequilibrium scheme is more accurate than the central-difference scheme. In addition, the flux computation rendered by the present scheme also preserves the parallel computation feature of the LBM, making the scheme more efficient than conventional finite-difference schemes in the study of large-scale problems. Finally, a comparison between the single-relaxation-time model and the MRT model is also conducted, and the results show that the MRT model is more accurate than the single-relaxation-time model, both in solving the convection-diffusion equation and in computing the flux. PMID- 25122409 TI - Real-space finite-difference calculation method of generalized Bloch wave functions and complex band structures with reduced computational cost. AB - Generalized Bloch wave functions of bulk structures, which are composed of not only propagating waves but also decaying and growing evanescent waves, are known to be essential for defining the open boundary conditions in the calculations of the electronic surface states and scattering wave functions of surface and junction structures. Electronic complex band structures being derived from the generalized Bloch wave functions are also essential for studying bound states of the surface and junction structures, which do not appear in conventional band structures. We present a novel calculation method to obtain the generalized Bloch wave functions of periodic bulk structures by solving a generalized eigenvalue problem, whose dimension is drastically reduced in comparison with the conventional generalized eigenvalue problem derived by Fujimoto and Hirose [Phys. Rev. B 67, 195315 (2003)]. The generalized eigenvalue problem derived in this work is even mathematically equivalent to the conventional one, and, thus, we reduce computational cost for solving the eigenvalue problem considerably without any approximation and losing the strictness of the formulations. To exhibit the performance of the present method, we demonstrate practical calculations of electronic complex band structures and electron transport properties of Al and Cu nanoscale systems. Moreover, employing atom-structured electrodes and jellium approximated ones for both of the Al and Si monatomic chains, we investigate how much the electron transport properties are unphysically affected by the jellium parts. PMID- 25122410 TI - Self-energy-modified Poisson-Nernst-Planck equations: WKB approximation and finite-difference approaches. AB - We propose a modified Poisson-Nernst-Planck (PNP) model to investigate charge transport in electrolytes of inhomogeneous dielectric environment. The model includes the ionic polarization due to the dielectric inhomogeneity and the ion ion correlation. This is achieved by the self energy of test ions through solving a generalized Debye-Huckel (DH) equation. We develop numerical methods for the system composed of the PNP and DH equations. Particularly, toward the numerical challenge of solving the high-dimensional DH equation, we developed an analytical WKB approximation and a numerical approach based on the selective inversion of sparse matrices. The model and numerical methods are validated by simulating the charge diffusion in electrolytes between two electrodes, for which effects of dielectrics and correlation are investigated by comparing the results with the prediction by the classical PNP theory. We find that, at the length scale of the interface separation comparable to the Bjerrum length, the results of the modified equations are significantly different from the classical PNP predictions mostly due to the dielectric effect. It is also shown that when the ion self energy is in weak or mediate strength, the WKB approximation presents a high accuracy, compared to precise finite-difference results. PMID- 25122411 TI - Path-integral Monte Carlo method for Renyi entanglement entropies. AB - We introduce a quantum Monte Carlo algorithm to measure the Renyi entanglement entropies in systems of interacting bosons in the continuum. This approach is based on a path-integral ground state method that can be applied to interacting itinerant bosons in any spatial dimension with direct relevance to experimental systems of quantum fluids. We demonstrate how it may be used to compute spatial mode entanglement, particle partitioned entanglement, and the entanglement of particles, providing insights into quantum correlations generated by fluctuations, indistinguishability, and interactions. We present proof-of principle calculations and benchmark against an exactly soluble model of interacting bosons in one spatial dimension. As this algorithm retains the fundamental polynomial scaling of quantum Monte Carlo when applied to sign problem-free models, future applications should allow for the study of entanglement entropy in large-scale many-body systems of interacting bosons. PMID- 25122412 TI - Generalized modification in the lattice Bhatnagar-Gross-Krook model for incompressible Navier-Stokes equations and convection-diffusion equations. AB - In this paper, two modified lattice Boltzmann Bhatnagar-Gross-Krook (LBGK) models for incompressible Navier-Stokes equations and convection-diffusion equations are proposed via the addition of correction terms in the evolution equations. Utilizing this modification, the value of the dimensionless relaxation time in the LBGK model can be kept in a proper range, and thus the stability of the LBGK model can be improved. Although some gradient operators are included in the correction terms, they can be computed efficiently using local computational schemes such that the present LBGK models still retain the intrinsic parallelism characteristic of the lattice Boltzmann method. Numerical studies of the steady Poiseuille flow and unsteady Womersley flow show that the modified LBGK model has a second-order convergence rate in space, and the compressibility effect in the common LBGK model can be eliminated. In addition, to test the stability of the present models, we also performed some simulations of the natural convection in a square cavity, and we found that the results agree well with those reported in the previous work, even at a very high Rayleigh number (Ra = 10(12)). PMID- 25122413 TI - Acoustic equations of state for simple lattice Boltzmann velocity sets. AB - The lattice Boltzmann (LB) method typically uses an isothermal equation of state. This is not sufficient to simulate a number of acoustic phenomena where the equation of state cannot be approximated as linear and constant. However, it is possible to implement variable equations of state by altering the LB equilibrium distribution. For simple velocity sets with velocity components xi(ialpha)?( 1,0,1) for all i, these equilibria necessarily cause error terms in the momentum equation. These error terms are shown to be either correctable or negligible at the cost of further weakening the compressibility. For the D1Q3 velocity set, such an equilibrium distribution is found and shown to be unique. Its sound propagation properties are found for both forced and free waves, with some generality beyond D1Q3. Finally, this equilibrium distribution is applied to a nonlinear acoustics simulation where both mechanisms of nonlinearity are simulated with good results. This represents an improvement on previous such simulations and proves that the compressibility of the method is still sufficiently strong even for nonlinear acoustics. PMID- 25122414 TI - Electronically- and crystal-structure-driven magnetic structures and physical properties of RScSb (R = rare earth) compounds: a neutron diffraction, magnetization and heat capacity study. AB - The synthesis of the new equiatomic RScSb (R = La-Nd, Sm, Gd-Tm, Lu, Y) compounds has been recently reported. These rare earth compounds crystallize in two different crystal structures, adopting the CeScSi-type (I4/mmm) for the lighter R (La-Nd, Sm) and the CeFeSi-type (P4/nmm) structure for the heavier R (R = Gd-Tm, Lu, Y). Here we report the results of neutron diffraction, magnetization and heat capacity measurements on some of these compounds (R = Ce, Pr, Nd, Gd and Tb). Band structure calculations have also been performed on CeScSb and GdScGe (CeScSi type), and on GdScSb and TbScSb (CeFeSi-type) to compare and understand the exchange interactions in CeScSi and CeFeSi structure types. The neutron diffraction investigation shows that all five compounds order magnetically, with the highest transition temperature of 66 K in TbScSb and the lowest of about 9 K in CeScSb. The magnetic ground state is simple ferromagnetic (tau = [0 0 0]) in CeScSb, as well in NdScSb for 32 > T > 22 K. Below 22 K a second magnetic transition, with propagation vector tau = [1/4 1/4 0], appears in NdScSb. PrScSb has a magnetic structure within, determined by mostly ferromagnetic interactions and antiferromagnetic alignment of the Pr-sites connected through the I-centering (tau = [1 0 0]). A cycloidal spiral structure with a temperature dependent propagation vector tau = [delta delta 1/2] is found in TbScSb. The results of magnetization and heat capacity lend support to the main conclusions derived from neutron diffraction. As inferred from a sharp peak in magnetization, GdScSb orders antiferromagnetically at 56 K. First principles calculations show lateral shift of spin split bands towards lower energy from the Fermi level as the CeScSi type structure changes to the CeFeSi-type structure. This rigid shift may force the system to transform from exchange split ferromagnetic state to the antiferromagnetic state in RScSb compounds (as seen for example in GdScSb and TbScSb) and is proposed to explain the change-over from a ferromagnetic structure as found in the CeScSi-type compounds CeScSb and NdScSb to the antiferromagnetic state as found in TbScSb and GdScSb. PMID- 25122417 TI - A note from the Editor-in-Chief on enhancements to the journal. PMID- 25122415 TI - Construction and characterization of a repetitive DNA library in Parodontidae (Atinopterygii:Characiformes): a genomic and evolutionary approach to the degeneration of the w sex cromosome. AB - Repetitive DNA sequences, including tandem and dispersed repeats, comprise a large portion of eukaryotic genomes and are important for gene regulation, sex chromosome differentiation, and karyotype evolution. In Parodontidae, only the repetitive DNAs WAp and pPh2004 and rDNAs were previously studied using fluorescence in situ hybridization. This study aimed to build a library of repetitive DNA in Parodontidae. We isolated 40 clones using Cot-1; 17 of these clones exhibited similarity to repetitive DNA sequences, including satellites, minisatellites, microsatellites, and class I and class II transposable elements (TEs), from Danio rerio and other organisms. The physical mapping of the clones to chromosomes revealed the presence of a satellite DNA, a Helitron element, and degenerate short interspersed element (SINE), long interspersed element (LINE), and tc1-mariner elements on the sex chromosomes. Some clones exhibited dispersed signals; other sequences were not detected. The 5S rDNA was detected on an autosomal pair. These elements likely function in the molecular degeneration of the W chromosome in Parodontidae. Thus, the location of these elements on the chromosomes is important for understanding the function of these repetitive DNAs and for integrative studies with genome sequencing. The presented data demonstrate that an intensive invasion of TEs occurred during W sex chromosome differentiation in the Parodontidae. PMID- 25122418 TI - Practice makes perfect protocols: the Canadian anaplastic lymphoma kinase study. PMID- 25122419 TI - RET mutations in neuroendocrine tumors: including small-cell lung cancer. PMID- 25122420 TI - An evidence-based determination of issues affecting quality of life and patient reported outcomes in lung cancer: results of a survey of 660 patients. AB - INTRODUCTION: Identifying issues of importance for patients with lung cancer is critical in individualizing care and developing effective quality of life instruments based on evidence. This study was conducted to provide enhanced content validity for measures assessing quality of life and patient-reported outcomes (PROs). METHODS: We conducted an anonymous, cross-sectional, electronic web-based survey of 660 lung cancer patients. The survey asked patients to rank 20 quality of life issues on a 5-point scale ranging from "not important at all" to "very important". Analysis was obtained using key factors such as stage of disease, performance status, and gender. RESULTS: The survey was completed by 297 males and 363 females (median age 62 years). The top five rated issues were: quality of life, maintaining independence, ability to perform normal activities, ability to sleep, and not being fatigued. The issues of importance were all ranked, using the two highest categories ("very important" and "important") by at least 90% of patients. Although symptoms are important to patients, they were not the most highly ranked issues of concern; instead, global issues illustrating the effect of the symptoms on the patient, such as quality of life, maintaining independence, and performing normal activities were ranked highest. CONCLUSIONS: This is the largest analysis of evidence-based data determining content validity for quality of life and PROs as indicated by patients. These results provide greater confidence that the content of lung cancer quality of life measures is appropriate. In addition, the survey clearly demonstrates that PRO measures that only evaluate symptoms are not fully responding to patient-expressed needs. PMID- 25122421 TI - Association of patient-provider communication domains with lung cancer treatment. AB - BACKGROUND: Patient-physician communication is critical for helping patients understand and complete the complex steps needed to diagnose stage and treat lung cancer. We assessed which domains of patient-physician communication about lung cancer and its treatment are associated with receipt of disease-directed, stage appropriate treatment. METHODS: Patients with recently diagnosed lung cancer were recruited from four medical centers in New York City from 2008 to 2011. Participants were surveyed about discussions with physicians regarding treatment, symptoms, and needs. Multiple regression analysis and structural equation modeling were used to assess which communication factors were associated with disease treatment. RESULTS: Of the 352 participants, 191 (54%) received disease directed, stage-appropriate treatment. Unadjusted associations between communication items and treatment found that participants who felt that their physicians explained the risks and disadvantages of lung cancer treatment (p < 0.01), discussed their chances of cure (p = 0.02), discussed goals of treatment (p < 0.01), or who were warm and friendly (p = 0.04) were more likely to undergo treatment. Three communication domains were identified: treatment information, physician support, and patient symptoms/needs. After adjusting for known determinants of lung cancer treatment, increased treatment information was associated with higher probability of cancer-directed treatment (p = 0.003). Other communication domains (physician support or patient symptoms/needs) were not independent predictors of treatment (p > 0.05 for both comparisons). CONCLUSION: These data suggest that treatment information is particularly important for increasing the probability of cancer-directed therapy among lung cancer patients. Clinicians should ensure that they clearly discuss treatment goals and options with patients while maintaining empathy, supporting patient needs, and addressing symptoms. PMID- 25122422 TI - Canadian anaplastic lymphoma kinase study: a model for multicenter standardization and optimization of ALK testing in lung cancer. AB - INTRODUCTION: Fluorescence in situ hybridization (FISH) is currently the standard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a screening and alternative diagnostic method. The Canadian ALK (CALK) study was initiated to implement a multicenter optimization and standardization of laboratory developed ALK IHC and FISH tests across 14 hospitals. METHODS: Twenty eight lung adenocarcinomas with known ALK status were used as blinded study samples. Thirteen laboratories performed IHC using locally developed staining protocols for 5A4, ALK1, or D5F3 antibodies; results were assessed by H-score. Twelve centers conducted FISH using protocols based on Vysis' ALK break-apart FISH kit. Initial IHC results were used to optimize local IHC protocols, followed by a repeat IHC study to assess the results of standardization. Three laboratories conducted a prospective parallel IHC and FISH analysis on 411 consecutive clinical samples using post-validation optimized assays. RESULTS: Among study samples, FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors. Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68, respectively. IHC optimization improved the intraclass correlation coefficients to 0.94. Factors affecting FISH scoring and outliers were identified. Post-optimization concurrent IHC/FISH testing in 373 informative cases revealed 100% sensitivity and specificity for IHC versus FISH. CONCLUSIONS: Multicenter standardization study may accelerate the implementation of ALK testing protocols across a country/region. Our data support the use of an appropriately validated IHC assay to screen for ALK+ lung cancers. PMID- 25122423 TI - Inherited variation in the ATP-binding cassette transporter ABCB1 and survival after chemotherapy for stage III-IV lung cancer. AB - BACKGROUND: The ATP-binding cassette transporter gene ABCB1 and the glutathione S transferase gene GSTP1 code for a multidrug resistance protein and for a detoxifying phase II metabolic enzyme, respectively, with substrate specificities that include chemotherapy drugs often used to treat lung cancer. METHODS: We genotyped 11 ABCB1 and eight GSTP1 single nucleotide polymorphisms (SNPs) in 698 white lung cancer patients (all current or former cigarette smokers) and used log rank test statistics and proportional hazards regression to evaluate associations between SNP genotype and survival. RESULTS: Using data from all 698 cases, one SNP in ABCB1 (rs2235013) was statistically significantly associated with overall survival (p = 0.038, log-rank test). Chemotherapy and stage jointly (p = 0.025) significantly modified the association between rs2235013 and survival, with statistically significant (p = 0.013, log-rank test) association observed in the subgroup of stage III to IV lung cancer patients who received chemotherapy as part of their first course of treatment (n = 160; 93.1% nonsmall cell). Patients who inherited the minor T allele at ABCB1 rs2235013 experienced better overall survival and recurrence-free survival (hazard ratio, per minor T allele, [95% confidence interval]: 0.66 [0.49-0.90] and 0.55 [0.31-0.95], respectively; adjusted for year of diagnosis, sex, age at diagnosis, cigarette pack years, and stage). In addition, in the advanced stage chemotherapy-treated subgroup, four ABCB1 SNPs (rs6949448, rs2235046, rs1128503, and rs10276036) in mutual high linkage disequilibrium with rs2235013 and an independent ABCB1 SNP (rs1045642) showed statistically significant association (p < 0.05) with survival. CONCLUSIONS: Inherited variation in ABCB1 may affect survival specifically in advanced stage lung cancer patients who receive chemotherapy. PMID- 25122424 TI - A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage I to IIIA non-small-cell lung cancers. AB - INTRODUCTION: While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene promoter methylation in early-stage non-small-cell lung cancers (NSCLCs), few studies have investigated this question prospectively. METHODS: Primary tumor tissue from patients with resected pathologic stage I to IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual tumor suppressor genes (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. RESULTS: A total of 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (62%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p = 0.03). The total number of genes with methylated promoters did not correlate with RFS (p = 0.89) or OS (p = 0.55). CONCLUSION: Contrary to data established by previous retrospective series, tumor suppressor gene promoter methylation (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs. PMID- 25122425 TI - The prognostic significance of focal adhesion kinase expression in stage I non small-cell lung cancer. AB - INTRODUCTION: Focal adhesion kinase (FAK) plays a significant role in cancer cell survival signaling and is overexpressed in various malignancies, including lung cancer. Previous studies suggest that FAK overexpression is an independent factor predicting poor prognosis in non-small-cell lung cancer (NSCLC). The aim of this study is to confirm these findings specifically in stage I NSCLC. METHODS: A retrospective tissue microarray (TMA) analysis of FAK protein expression by immunohistochemistry was performed in 157 surgically resected stage I NSCLC specimen and in the corresponding matched normal lung tissue. The FAK 4.47 monoclonal antibody was used for FAK immunostaining. The scoring system of triplicate tumor cores included intensity of staining plus extent of staining for a composite score that ranged from 0 to 6. The association between FAK score and survival was evaluated. RESULTS: There were 103 stage IA and 54 stage IB patients, with mean follow-up of 5.5 years. Normal lung alveoli and interstitial tissue had mean FAK score of 0 (median score 0, range 0 to 2). Tumor samples had mean FAK score 3.1 (median score 3.5, range 0-6), with 57% of the samples having FAK score >= 3. Continuous FAK score was not associated with demographic data, tumor histology, or grade, nor survival in this cohort of stage I NSCLC patients. CONCLUSIONS: FAK is expressed in more than 50% of stage I NSCLC lung cancer but not in normal lung alveoli and interstitial tissue. FAK expression is not associated with survival outcome in this North American cohort. PMID- 25122426 TI - DNMT3B overexpression by deregulation of FOXO3a-mediated transcription repression and MDM2 overexpression in lung cancer. AB - INTRODUCTION: DNA methyltransferase 3B (DNMT3B) contributes to de novo DNA methylation and its overexpression promotes tumorigenesis. However, whether DNMT3B is upregulated by transcriptional deregulation remains unclear. METHODS: We studied the transcriptional repression of DNMT3B by forkhead O transcription factor 3a (FOXO3a) in lung cancer cell, animal, and clinical models. RESULTS: The results of luciferase reporter assay showed that FOXO3a negatively regulated DNMT3B promoter activity by preferentially interacting with the binding element FOXO3a-E (+166 to +173) of DNMT3B promoter. Ectopically overexpressed FOXO3a or combined treatment with doxorubicin to induce FOXO3a nuclear accumulation further bound at the distal site, FOXO3a-P (-249 to -242) by chromatin immunoprecipitation assay. Knockdown of FOXO3a resulted in an open chromatin structure and high DNMT3B mRNA and protein expression. Abundant FOXO3a repressed DNMT3B promoter by establishing a repressed chromatin structure. Note that FOXO3a is a degradation substrate of MDM2 E3-ligase. Cotreatment with doxorubicin and MDM2 inhibitor, Nutlin-3, further enforced abundant nuclear accumulation of FOXO3a resulting in decrease expression of DNMT3B leading to synergistic inhibition of tumor growth and decrease of methylation status on tumor suppressor genes in xenograft specimens. Clinically, lung cancer patients with DNMT3B high, FOXO3a low, and MDM2 high expression profile correlated with poor prognosis examined by immunohistochemistry and Kaplan-Meier survival analysis. CONCLUSIONS: We reveal a new mechanism that FOXO3a transcriptionally represses DNMT3B expression and this regulation can be attenuated by MDM2 overexpression in human lung cancer model. Cotreatment with doxorubicin and Nutlin-3 is a novel therapeutic strategy through epigenetic modulation. PMID- 25122427 TI - RET mutation and expression in small-cell lung cancer. AB - BACKGROUND: There is growing interest in defining the somatic mutations associated with small-cell lung cancer (SCLC). Unfortunately, a serious blockade to genomic analyses of this disease is a limited access to tumors because surgery is rarely performed. We used our clinical/pathologic database of SCLC patients to determine the availability of biopsy specimens that could be used for genomic studies and to identify tumors for initial oncogene analysis. METHODS: DNA was extracted from six tumors, three primary and three metastatic, and analyzed by SEQUENOM platform technology. RESULTS: Primary-resected tumor tissue represents less than 3% of all diagnostic specimens in this disease, highlighting the limited access to tissue sufficient for comprehensive genomic analyses. We identified an activating M918T RET somatic mutation in a metastatic SCLC tumor specimen. Bioinformatic search identified RET mutations in other SCLC studies. Stable overexpression of both mutant M918T and wild-type RET in two SCLC cell lines, H1048 and SW1271, activated ERK signaling, MYC expression, and increased cell proliferation, particularly by mutant RET. Stable cells became sensitized to the RET tyrosine kinase inhibitors, vandetanib and ponatinib. Further analysis of RET mRNA expression in SCLC revealed wide variability in both cells and tumors, and SCLC cells demonstrated significantly higher RET expression compared with adenocarcinoma lung cells. CONCLUSIONS: Our data suggest that a subpopulation of SCLC patients may derive benefit from tyrosine kinase inhibitors targeting RET. Coupled with the presence of RET fusion proteins in non-small-cell lung cancer, our data indicate an emerging role for RET in SCLC. PMID- 25122428 TI - Therapeutic priority of the PI3K/AKT/mTOR pathway in small cell lung cancers as revealed by a comprehensive genomic analysis. AB - INTRODUCTION: The information regarding therapeutically relevant genomic alterations in small cell lung cancer (SCLC) is not well developed. We analyzed the SCLC genome using an integrative approach to stratify the targetable alterations. METHODS: We performed whole exon sequencing (n = 51) and copy number analysis (n =47) on surgically resected tumors and matched normal tissue samples from treatment-naive Japanese SCLC patients. RESULTS: The demographics of the 51 patients included in this study were as follows: median age, 67 years (range, 42 86 years); female, 9 (18%); history of smoking, 50 (98%); and pathological stage I/II/III/IV, 28/13/9/1, respectively. The average number of nonsynonymous mutations was 209 (range, 41-639; standard deviation, 130). We repeatedly confirmed the high prevalence of inactivating mutations in TP53 and RB1, and the amplification of MYC family members. In addition, genetic alterations in the PI3K/AKT/mTOR pathway were detected in 36% of the tumors: PIK3CA, 6%; PTEN, 4%; AKT2, 9%; AKT3, 4%; RICTOR, 9%; and mTOR, 4%. Furthermore, the individual changes in this pathway were mutually exclusive. Importantly, the SCLC cells harboring active PIK3CA mutations were potentially targetable with currently available PI3K inhibitors. CONCLUSIONS: The PI3K/AKT/mTOR pathway is distinguishable in SCLC genomic alterations. Therefore, a sequencing-based comprehensive analysis could stratify SCLC patients by potential therapeutic targets. PMID- 25122429 TI - Safety and effectiveness of bevacizumab-containing treatment for non-small-cell lung cancer: final results of the ARIES observational cohort study. AB - INTRODUCTION: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, was approved by the US Food and Drug Administration for the treatment of advanced non-small-cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. ARIES (Avastin Regimens: Investigation of Effectiveness and Safety), a prospective observational cohort study, evaluated outcomes in a large, community-based population of patients with first-line NSCLC. METHODS: From 2006 to 2009, ARIES enrolled patients with locally advanced or metastatic NSCLC who were eligible for bevacizumab, excluding those with predominantly squamous histology. Patients were required to provide informed consent and to have initiated bevacizumab with chemotherapy within 4 months before enrollment. There were no protocol-defined treatments or assessments. The dosing of bevacizumab and chemotherapy, and the choice of chemotherapy regimen, was at the discretion of the treating physician. RESULTS: ARIES enrolled 1967 patients with first-line NSCLC. At study closure, median follow-up was 12.5 months (range, 0.2-65.5). Median age was 65 years (range, 31 93), and 252 patients (12.8%) identified as never smokers. Median progression free survival was 6.6 months (95% confidence interval, 6.3-6.9), and median overall survival was 13.0 months (95% confidence interval, 12.2-13.8) with first line bevacizumab plus chemotherapy. Incidences of bevacizumab-associated adverse events (19.7% overall) were consistent with those in randomized controlled trials of bevacizumab in NSCLC. CONCLUSION: Results from ARIES demonstrate similar outcomes to randomized controlled trials of bevacizumab when added to standard chemotherapy in a real-world patient population with advanced NSCLC. PMID- 25122430 TI - Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free tumor DNA as a surrogate for determination of EGFR status. AB - INTRODUCTION: In the phase IV, open-label, single-arm study NCT01203917, first line gefitinib 250 mg/d was effective and well tolerated in Caucasian patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (previously published). Here, we report EGFR mutation analyses of plasma-derived, circulating-free tumor DNA. METHODS: Mandatory tumor and duplicate plasma (1 and 2) baseline samples were collected (all screened patients; n = 1060). Preplanned, exploratory analyses included EGFR mutation (and subtype) status of tumor versus plasma and between plasma samples. Post hoc, exploratory analyses included efficacy by tumor and plasma EGFR mutation (and subtype) status. RESULTS: Available baseline tumor samples were 1033 of 1060 (118 positive of 859 mutation status known; mutation frequency, 13.7%). Available plasma 1 samples were 803 of 1060 (82 positive of 784 mutation status known; mutation frequency, 10.5%). Mutation status concordance between 652 matched tumor and plasma 1 samples was 94.3% (95% confidence interval [CI], 92.3-96.0) (comparable for mutation subtypes); test sensitivity was 65.7% (95% CI, 55.8 74.7); and test specificity was 99.8% (95% CI, 99.0-100.0). Twelve patients of unknown tumor mutation status were subsequently identified as plasma mutation positive. Available plasma 2 samples were 803 of 1060 (65 positive of 224 mutation status-evaluable and -known). Mutation status concordance between 224 matched duplicate plasma 1 and 2 samples was 96.9% (95% CI, 93.7-98.7). Objective response rates are as follows: mutation-positive tumor, 70% (95% CI, 60.5-77.7); mutation-positive tumor and plasma 1, 76.9% (95% CI, 65.4-85.5); and mutation positive tumor and mutation-negative plasma 1, 59.5% (95% CI, 43.5-73.7). Median progression-free survival (months) was 9.7 (95% CI, 8.5-11.0; 61 events) for mutation-positive tumor and 10.2 (95% CI, 8.5-12.5; 36 events) for mutation positive tumor and plasma 1. CONCLUSION: The high concordance, specificity, and sensitivity demonstrate that EGFR mutation status can be accurately assessed using circulating-free tumor DNA. Although encouraging and suggesting that plasma is a suitable substitute for mutation analysis, tumor tissue should remain the preferred sample type when available. PMID- 25122431 TI - Reproducibility of histopathological diagnosis in poorly differentiated NSCLC: an international multiobserver study. AB - INTRODUCTION: The 2004 World Health Organization classification of lung cancer contained three major forms of non-small-cell lung cancer: squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of this study was first, to assess the reproducibility of a set of histopathological features for SqCC in relation to other poorly differentiated non-small-cell lung cancers and second, to assess the value of immunohistochemistry in improving the diagnosis. METHODS: Resection specimens (n = 37) with SqCC, large cell carcinoma, basaloid carcinoma, sarcomatoid carcinoma, lymphoepithelial-like carcinoma, and solid AdC, were contributed by the participating pathologists. Hematoxylin and eosin (H&E) stained slides were digitized. The diagnoses were evaluated in two ways. First, the histological criteria were evaluated and the (differential) diagnosis on H&E alone was scored. Second, the added value of additional stains to make an integrated diagnosis was examined. RESULTS: The histologic criteria defining SqCC were consistently used, but in poorly differentiated cases they were infrequently present, rendering the diagnosis more difficult. Kappa scores on H&E alone were for SqCC 0.46, large cell carcinoma 0.25, basaloid carcinoma 0.27, sarcomatoid carcinoma 0.52, lymphoepithelial-like carcinoma 0.56, and solid AdC 0.21. The kappa score improved with the use of additional stains for SqCC (combined with basaloid carcinoma) to 0.57, for solid AdC to 0.63. CONCLUSION: The histologic criteria that may be used in the differential diagnosis of poorly differentiated lung cancer were more precisely refined. Furthermore, additional stains improved the reproducibility of histological diagnosis of SqCC and AdC, uncovering information that was not present in routine H&E stained slides. PMID- 25122432 TI - The prognostic impact of KRAS, its codon and amino acid specific mutations, on survival in resected stage I lung adenocarcinoma. AB - BACKGROUND: Despite complete surgical resection, patients with stage I non-small cell lung cancer (NSCLC) are at risk for disease recurrence. The impact of common oncogenic driver mutations on prognosis in stage I NSCLC is limited. The pure prognostic value of KRAS mutational status was explored in resected stage I lung adenocarcinoma. METHODS: Mutation status was tested in patients who had complete resection of stage I lung adenocarcinoma without any adjuvant therapy, using a multiplex polymerase chain reaction)-based assay. Disease-free survival (DFS) and overall survival (OS) were compared between patients with KRAS-mutant (KRAS-MUT), KRAS-MUT subtypes, and KRAS wild-type (KRAS-WT) tumors. RESULTS: A total of 312 patients were included in this analysis; 127 harbored KRAS mutations and 185 had KRAS-WT tumors. When compared with KRAS-WT, KRAS-MUT was associated with significantly shorter OS (hazard ratio 4.36, 95% confidence interval 2.09-9.07; p < 0.0001) and DFS (hazard ratio 3.62, 95% confidence interval 2.11-6.22; p < 0.0001). When stratifying KRAS-WT patients based on EGFR status, KRAS-MUT patients had worse OS (p = 0.0001) and DFS (p < 0.0001) than patients with EGFR MUT and EGFR-WT/KRAS-WT (WT/WT). Patients with codon 12 mutations had superior DFS (p = 0.0314), but there were no differences in OS compared with mutations found in codons 13 and 61 (p = 0.1772). We observed better DFS associated with G12C/G12V mutations compared with other amino acid specific KRAS mutations (p = 0.0271) with a trend towards improved OS (p = 0.0636). Multivariate analysis identified KRAS mutation as independent predictor of worse OS (p = 0.001) and DFS (p < 0.0001). CONCLUSION: KRAS is an independent prognostic marker in resected stage I lung adenocarcinoma. Differential outcomes are associated with codon and amino acid specific KRAS mutations. PMID- 25122433 TI - Toxicities of organs at risk in the mediastinal and hilar regions following stereotactic body radiotherapy for centrally located lung tumors. AB - INTRODUCTION: We investigated tolerable doses to organs at risk (OARs) in the mediastinum and pulmonary hilum following stereotactic body radiotherapy for centrally located lung tumors. METHODS: Between 2005 and 2012, 381 patients with lung tumors were treated with stereotactic body radiotherapy of 40 to 60 Gy in five fractions. From among these patients, we extracted those who received greater than 25 Gy irradiation to OARs and analyzed dosimetric factors in relation to grade 3 to 5 toxicities. RESULTS: In total, 398 OARs in 133 patients were analyzed, with a median follow-up of 33 (range, 3-87) months. The numbers receiving greater than 25 Gy irradiation to the aorta, vena cava, pulmonary artery, pulmonary vein, bronchus, trachea, heart, and esophagus were 72, 33, 73, 60, 55, 13, 69, and 23, respectively. The corresponding median Dmax 0.5 ml were 43.8, 32.0, 32.2, 29.1, 28.4, 28.7, 41.1, and 21.7 Gy. Of these patients, two developed grade 5 and one grade 3 hemoptysis, and two had grade 3 obstructive pneumonia. Two patients with grade 5 hemoptysis received high doses at the pulmonary artery and bronchus (59.2 and 54.4 Gy, and 61.3 and 59.6 Gy, respectively). No other grade 3 to 5 toxicities occurred. CONCLUSION: Therapeutic indications and dose-intensity should be carefully determined for patients with central tumors, especially when doses to the pulmonary artery and bronchus in the pulmonary hilum exceed 50 Gy. Tolerable doses for other OARs might, however, be higher than in this study, though longer follow-up is necessary to assess this possibility. PMID- 25122434 TI - Can computed tomography characteristics predict outcomes in patients undergoing radial endobronchial ultrasound-guided biopsy of peripheral lung lesions? AB - INTRODUCTION: Percutaneous computed tomography (CT)-guided lung biopsy is a standard minimally invasive technique for sampling peripheral lung lesions. Radial endobronchial ultrasound (EBUS) offers an alternative approach but it has yet to be defined which patients are most suited to this procedure. The primary aim of this study was to investigate whether CT characteristics could predict the success of radial EBUS-guided sampling. METHODS: The University Hospital South Manchester provides a radial EBUS service, under conscious sedation without fluoroscopy, double-hinged curettes, or guide sheaths, to a large cancer Network in the United Kingdom. This retrospective analysis of a prospectively maintained database included all patients undergoing radial EBUS from January 2011 to June 2013. Lesion size, structure, location, and presence of a bronchus sign on thoracic CT were analyzed against predefined outcomes using multivariate analysis. RESULTS: One-hundred and seventeen patients underwent radial EBUS in the study period (mean age 69.5, mean lesion size 36.6 mm). The presence of a bronchus sign on CT was the only independent predictor of all predefined outcomes: (1) lesion identification with radial EBUS, (2) positioning of probe within the center of the lesion, and (3) accurate pathological diagnosis; odds ratio (OR) 31.1 (7.8-123.9, p < 0.0001), OR 44.8 (5.6-354.9, p < 0.0001) and OR 46.6 (11.1-195.3, p < 0.0001) respectively. The sensitivity and diagnostic accuracy for those patients with a bronchus sign on CT was 87.3% and 86.7% compared with 12.5% and 11.1% for those lacking the bronchus sign. DISCUSSION: The patients most likely to benefit from radial EBUS, without the use of adjuncts, are those with a bronchus sign on CT. PMID- 25122435 TI - Re-evaluating the optimal radiation dose for definitive chemoradiotherapy for esophageal squamous cell carcinoma. AB - BACKGROUND: The optimal radiation dose for treating esophageal squamous cell carcinoma (ESCC) has long been debated. We evaluated if doses greater than 50.4 Gy delivered with modern techniques are beneficial in terms of tumor control, survival, and toxicity. METHODS: We included 193 consecutive patients with ESCC treated with definitive concurrent chemoradiotherapy from 1998 to 2012. Patients were treated to a dose of <=50.4 Gy (low-dose, n = 137) or greater than 50.4 Gy (high-dose, n = 56). Tumor response, local-regional control, survival, and treatment toxicity were compared between groups. RESULTS: High-dose group had a significantly lower local failure rate (17.9% versus 34.3%, p = 0.024) and a marginal better 5-year local-regional failure-free survival (68.7% versus 55.9%, p = 0.052) than the low-dose group. No significant differences were found between high- and low-dose groups in tumor complete response rate (p = 0.975), regional failure rate (p = 0.336), distant metastasis rate (p = 0.390), or 5-year overall survival (p = 0.617). No difference in the incidence of toxic effects was observed between the two groups except for grade 3 skin reaction (12.5% [high] versus 2.2% [low], p < 0.001) and grade greater than or equal to 3 esophageal stricture (32.1% [high] versus 18.2% [low], p = 0.037). CONCLUSIONS: Local tumor control might be improved by higher dose of greater than 50.4 Gy, when delivered with modern techniques and concurrent chemotherapy, at the consequence of increased toxicity without impact on overall survival. PMID- 25122436 TI - Clinical characteristics, tumor, node, metastasis status, and mutation rate in domain of epidermal growth factor receptor gene in serbian patients with lung adenocarcinoma. AB - OBJECTIVE: Mutation rate in domain of EGFR gene varies between populations of lung cancer patients. Primary aim of this study was to analyze clinical and pathological characteristics, and tumor, node, metastasis status and stage of diseases, in relation to mutation status. METHODS: After histological confirmation of lung adenocarcinoma tissue obtained during bronchoscopy was consecutively sent for EGFR testing. Genomic DNA extraction was performed with the QIAamp DNA FFPE Tissue kit. Clinical data for multivariate analysis were extracted from hospital based-lung cancer registry. RESULTS: Among 360 tested patients, there was 67.8% males and 32.2% females, aged 61 +/- 9.8 years. Majority of patients were smokers (57.0%) with Eastern Cooperative Oncology Group 1 performance status (92.2%). Mutation in EGFR gene was detected in 42 (11.7%) patients. Deletion in exon 19 was detected in 24 (6.7%) patients, mutation in exon 21 in 17 (4.7%), and mutation in exon 18 in one patient (0.3%). Patients were mostly diagnosed in stage IV adenocarcinoma (74.4%). Statistically significant differences were determined in relation to smoking (p < 0.001), T descriptor (size; p = 0.019) and gender (p = 0.002). CONCLUSIONS: Mutation rate in domain of EGFR gene in investigated lung cancer population is in range with reported data in Caucasian race. Smoking, T descriptor and gender were found to be related to the EGFR status. PMID- 25122438 TI - Popcorn in the lung. PMID- 25122437 TI - Biomarker analyses from a randomized, placebo-controlled, phase IIIb trial comparing bevacizumab with or without erlotinib as maintenance therapy for the treatment of advanced non-small-cell lung cancer (ATLAS). AB - INTRODUCTION: ATLAS compared bevacizumab plus erlotinib (B+E) with bevacizumab plus placebo (B+P) as maintenance therapy after first-line bevacizumab plus chemotherapy (B+C) for advanced non-small-cell lung cancer (NSCLC). Prespecified biomarkers were prospectively evaluated. METHODS: Tumor samples were analyzed for: epidermal growth factor receptor (EGFR) expression (immunohistochemistry [IHC]); EGFR gene copy number (fluorescence in-situ hybridization [FISH]); EGFR mutations (exon 19 deletions/L858R mutations); and KRAS mutations (exons 2/3). Progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS: Of 743 patients randomized to receive maintenance treatment (after four cycles of B+C without progression), 190 (B+E) and 177 (B+P) were evaluable for biomarker status. Median PFS (from randomization) was 4.4 months (B+E) versus 3.7 months (B+P; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.99), which was numerically similar to the intent-to-treat PFS. PFS benefit of B+E was observed across most biomarker subgroups. EGFR IHC, EGFR FISH, and EGFR/KRAS mutation status were not predictive of outcome. B+E-treated patients with EGFR mutation-positive NSCLC had longer PFS compared with B+P-treated patients (HR, 0.44; 95% CI, 0.22-0.86; p = 0.0139). Patients with KRAS wild-type disease had significant PFS improvements with B+E, compared with B+P (HR, 0.66; 95% CI, 0.485 0.914; p = 0.0105). No OS benefit of B+E was observed. CONCLUSIONS: Patients with KRAS wild-type or EGFR mutation-positive NSCLC derived PFS benefits from B+E. However, EGFR IHC, EGFR FISH, and EGFR or KRAS mutation status were not strongly predictive of survival. A larger sample size would be needed to confirm the initial trends observed in this study. PMID- 25122439 TI - Effective treatment with icotinib in primary adenoid cystic carcinoma of the lung with liver metastasis. PMID- 25122440 TI - Cisplatin or Carboplatin for advanced non-small-cell lung cancer? PMID- 25122441 TI - EGFR mutations in Asian patients with advanced lung adenocarcinoma. PMID- 25122442 TI - EGFR mutation detection by polymerase chain reaction-direct sequencing and allele specific real-time PCR. PMID- 25122443 TI - Prevalence of selected chronic digestive conditions, United States - july december 1968. AB - This report on chronic digestive conditions is the first of a new series of reports on the prevalence of selected chronic conditions" based on data collected as a part of the Health Interview Survey. Estimates of the prevalence of chronic diseases or impairments have been made from information reported in the Health Interview Survey since its inception in July of 1957. Since that time efforts have been made to improve the quality of the data on the prevalence of chronic conditions. Chronic conditions reported in interviews may be described as those of which the respondent is aware and which he is willing to report to an interviewer. The diagnostic accuracy of reported conditions is dependent on the information the attending physician has passed on to the family or, in the absence of medical attention, on the previous medical experience or education of the family. Prior to 1968 in the Health Interview Survey an attempt was made to obtain data on all chronic conditions that respondents had had during the. 12 month period before the date of the interview; checklists of about 40 to 50 chronic conditions and impairments were used. Beginning in 1968 the procedure was changed, and data were obtained only for chronic conditions within one system of conditions each year (although data on all conditions causing long term limitations of activity, disability days, and physician visits were still obtained). In 1968 respondents were read a list of 25 conditions, the majority of which were digestive conditions (see question 16a, appendix III). A more detailed discussion of basic changes made in 1968 can be found in Vital and Health Statistics, Series 2, Number 48. PMID- 25122444 TI - A bispecific fusion protein and a bifunctional enediyne-energized fusion protein consisting of TRAIL, EGFR peptide ligand, and apoprotein of lidamycin against EGFR and DR4/5 show potent antitumor activity. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mainly induces apoptosis through the extrinsic death receptor-induced pathway by ligation with death receptor 4 (DR4) and death receptor 5 (DR5). On the basis of the antitumor activity to cancer cells and no cytotoxity to normal cells of TRAIL and the target of the epidermal growth factor receptor (EGFR) ligand peptide, the study constructed a new bispecific fusion protein and a new bifunctional enediyne energized fusion protein and investigated their antitumor efficacy. Bispecific fusion protein Ec-LDP-TRAIL showed potent binding activity to cancer cell lines with a high expression of EGFR or DR4/DR5 such as A431 and H460 cells, whereas poor binding activity to NIH/3T3 cells with low expressing EGFR and DR4/DR5. Ec LDP-TRAIL also showed more potent cytotoxicity to A431 and H460 cells than Ec LDP, which could result from the TRAIL-inducing apoptosis. Results of an in-vivo efficacy study showed that Ec-LDP-TRAIL at a dose of 10 mg/kg decreased the growth of epidermoid carcinoma A431 xenografts by 80.19% (P < 0.01) on day 26. Immunohistochemical detection of nuclear antigen factor Ki-67 suggested that Ec LDP-TRAIL effectively induced cell necrosis and inhibited cell proliferation of tumor. From IC50 values, bispecific and bifunctional energized fusion protein Ec LDP-TRAIL-AE was more potent and selective in its cytotoxicity against different carcinoma cell lines than corresponding lidamycin in vitro and induction of the cleavage of poly(ADP-ribose)polymerase was observed in A431 cells treated with Ec LDP-TRAIL-AE and lidamycin, respectively. Ec-LDP-TRAIL-AE also significantly inhibited the growth of A431 xenografts in a nude mouse model. These properties suggested that Ec-LDP-TRAIL and Ec-LDP-TRAIL-AE may be promising candidates for targeted cancer therapy. PMID- 25122445 TI - Surgical site infections after deep brain stimulation surgery: frequency, characteristics and management in a 10-year period. AB - BACKGROUND/AIMS: Deep brain stimulation (DBS) implant infection is a feared complication, as it is difficult to manage and leads to increased patient morbidity. We wanted to assess the frequency and possible risk factors of DBS related infections at our centre. In the purpose of evaluating treatment options, we also analyzed treatment, and the clinical and microbiological characteristics of the infections. METHODS: Electronic medical records of all patients undergoing DBS surgery at our centre, from 2001 through 2010, were retrospectively reviewed. RESULTS: Of the 588 procedures performed 33 (5.6%) led to an infection. Some patients underwent several procedures, thus 32 out of totally 368 patients (8.7%), and 19 out of 285 patients (6.7%) who received primary lead implantation, developed an infection. Most infections (52%) developed within the first month and 79% within three months. In the majority of the infections (79%) hardware removal was performed. Staphylococcus aureus infections were the most frequent (36%), and more likely to have earlier onset, pus formation, a more aggressive development and lead to hardware removal. No risk factors were identified. CONCLUSIONS: Our results indicate that infections with more severe symptoms and growth of staphylococcus aureus should be treated with local hardware removal and antibiotic therapy. In other infections, an initial trial of antibiotic treatment could be considered. New knowledge about the microbiology of DBS related infections may lead to more effective antimicrobial treatment. PMID- 25122447 TI - Experimental parameterisation of principal physics in buoyancy variations of marine teleost eggs. AB - It is generally accepted that the high buoyancy of pelagic marine eggs is due to substantial influx of water across the cell membrane just before ovulation. Here we further develop the theoretical basis by applying laboratory observations of the various components of the fertilized egg in first-principle equations for egg specific gravity (rho(egg)) followed by statistical validation. We selected Atlantic cod as a model animal due to the affluent amount of literature on this species, but also undertook additional dedicated experimental works. We found that specific gravity of yolk plus embryo is central in influencing rho(egg) and thereby the buoyancy. However, our established framework documents the effect on rho(egg) of the initial deposition of the heavy chorion material in the gonad prior to spawning. Thereafter, we describe the temporal changes in rho(egg) during incubation: Generally, the eggs showed a slight rise in rho(egg) from fertilization to mid-gastrulation followed by a gradual decrease until full development of main embryonic organs just before hatching. Ontogenetic changes in rho(egg) were significantly associated with volume and mass changes of yolk plus embryo. The initial rho(egg) at fertilization appeared significantly influenced by the chorion volume fraction which is determined by the combination of the final chorion volume of the oocyte and of the degree of swelling (hydrolyzation) prior to spawning. The outlined principles and algorithms are universal in nature and should therefore be applicable to fish eggs in general. PMID- 25122448 TI - The impact of past direct-personal traumatic events on 12-month outcome in first episode psychotic mania: trauma and early psychotic mania. AB - OBJECTIVE: Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania. METHODS: Traumatic events were retrospectively evaluated from patient files in a sample of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point. RESULTS: Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the sample. Participants with past direct-personal trauma had significantly higher symptoms of mania (p=0.02), depression (p=0.03) and psychopathology (p=0.01) 12 months following their first episode compared to participants without past direct personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant (p=0.05); however, participants with past direct-personal trauma had significantly poorer social and occupational functioning (p=0.04) at the 12-month assessment with medium effect. CONCLUSIONS: Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent individuals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated. PMID- 25122450 TI - Theory of Mind and attachment styles in people with psychotic disorders, their siblings, and controls. AB - OBJECTIVE: Impaired Theory of Mind (ToM) and insecure (adult) attachment styles have been found in persons with schizophrenia as well as in their healthy siblings. ToM refers to the ability to infer mental states of self and others including beliefs and emotions. Insecure attachment is proposed to underlie impaired ToM, and comprises avoidant (discomfort with close relationships, high value of autonomy) and anxious (separation anxiety, dependency on others) attachment. Insight into the association between attachment style and ToM is clinically relevant, as it enhances our understanding and clinical approach to social dysfunction in schizophrenia. Therefore, we studied the association between insecure attachment styles and ToM in patients with schizophrenia, their siblings, and healthy controls. METHODS: A total of 111 patients with a diagnosis in the schizophrenia spectrum, 106 non-affected siblings and 63 controls completed the Psychosis Attachment Measure, the Conflicting Beliefs and Emotions, a subsection of the Wechsler Adult Intelligence Scale, and the Childhood Trauma Questionnaire-Short Form. Severity of symptoms was assessed with the Community Assessment of Psychic Experiences and the Positive and Negative Syndrome Scale. RESULTS: After controlling for sex, intelligence, history of trauma and symptom severity, avoidant attachment was significantly associated with cognitive as well as with affective ToM, showing U-shaped associations, indicating better ToM performance for patients with lower or higher levels of avoidant attachment compared to medium levels. Anxious attachment in patients was associated with more problems in cognitive ToM. CONCLUSION: The results from this study support the idea that an anxious attachment style is associated with worse ToM performance in patients. Results also suggested a potential protective role of higher levels of avoidant attachment on ToM. These findings bear clinical relevance, as activation of (insecure) attachment mechanisms may affect interpersonal relations, as well as therapeutic working alliance. Further clarification is needed, especially on associations between ToM and avoidant attachment. PMID- 25122449 TI - DSM-IV and DSM-5 social anxiety disorder in the Australian community. AB - OBJECTIVE: Current and accurate estimates of prevalence, correlates, comorbid concerns and treatment-seeking behaviours associated with disorders are essential for informing policy, clinical practice and research. The most recent snapshot of social anxiety disorder in Australia was published more than a decade ago, with significant changes to the accessibility of mental health treatment services and diagnostic measures occurring during this period. This paper aims to (i) update the understanding of social anxiety disorder, its associations and patterns of treatment-seeking behaviours in the Australian population, and (ii) explore the impact of revised diagnostic criteria detailed in the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) on prevalence estimates. METHODS: The National Survey of Mental Health and Wellbeing (NSMHWB) was conducted by the Australian Bureau of Statistics in 2007, collecting information from a nationally representative random sample of 8841 Australians aged 16-85 years. The presence of social anxiety disorder diagnostic criteria and related disorders were assessed over 12 months and lifetime periods using the World Mental Health Composite International Diagnostic Interview. RESULTS: Profiles of social anxiety disorder were consistent with previous estimates, with higher prevalence in females and younger age groups. Of the 8.4% of Australians meeting criteria for social anxiety disorder at some point in their lifetime (12 month prevalence 4.2%), a majority also experienced comorbid mental health concerns (70%). The revised performance-only specifier included in the DSM-5 was applicable to only 0.3% of lifetime cases. Just over 20% of people reporting social anxiety disorder as their primary concern sought treatment, most commonly through general practitioners. CONCLUSIONS: Social anxiety disorder continues to be prevalent in the Australian population and highly related to other disorders, yet few people experiencing social anxiety disorder seek treatment. PMID- 25122451 TI - Twelve-month prevalence and predictors of self-reported suicidal ideation and suicide attempt among Korean adolescents in a web-based nationwide survey. AB - OBJECTIVE: The suicide rate in South Korea was the highest among the Organisation for Economic Co-operation and Development (OECD) countries in 2011. Although the suicide rate in adolescents is lower than that of adults and is reported to be decreasing in young males in some countries, it has consistently increased in recent years in South Korea. We aimed to determine the prevalence, pattern, and predictors of suicidal ideation and attempt in the past 12 months. METHODS: A total sample of 72,623 adolescents aged 12-18 years who responded to a web-based anonymous self-reported survey between September and October 2010 was used for the analysis. RESULTS: The suicidal ideation and suicide attempt rates were 19.1% and 4.9%, respectively. Being female, having a poor perceived socioeconomic status and a poor perceived academic performance, subjective feelings of depression, cigarette smoking, alcohol use, perceived general medical health, and experiences of any involvement with sexual intercourse were the contributing factors that predicted elevated risks for suicidal ideation and suicide attempt. In contrast to previous reports in other countries, the suicide attempt rate in Korean female adolescents peaked at age 13 years, and there were no differences in suicidal ideation in females by age. There were no differences in both suicidal ideation and attempt rates in males by age. CONCLUSION: A multidisciplinary approach that takes into consideration the characteristics of Korean adolescents with suicidal ideation or suicide attempt is warranted for developing prevention and treatment programs. PMID- 25122452 TI - Unsupervised eye pupil localization through differential geometry and local self similarity matching. AB - The automatic detection and tracking of human eyes and, in particular, the precise localization of their centers (pupils), is a widely debated topic in the international scientific community. In fact, the extracted information can be effectively used in a large number of applications ranging from advanced interfaces to biometrics and including also the estimation of the gaze direction, the control of human attention and the early screening of neurological pathologies. Independently of the application domain, the detection and tracking of the eye centers are, currently, performed mainly using invasive devices. Cheaper and more versatile systems have been only recently introduced: they make use of image processing techniques working on periocular patches which can be specifically acquired or preliminarily cropped from facial images. In the latter cases the involved algorithms must work even in cases of non-ideal acquiring conditions (e.g in presence of noise, low spatial resolution, non-uniform lighting conditions, etc.) and without user's awareness (thus with possible variations of the eye in scale, rotation and/or translation). Getting satisfying results in pupils' localization in such a challenging operating conditions is still an open scientific topic in Computer Vision. Actually, the most performing solutions in the literature are, unfortunately, based on supervised machine learning algorithms which require initial sessions to set the working parameters and to train the embedded learning models of the eye: this way, experienced operators have to work on the system each time it is moved from an operational context to another. It follows that the use of unsupervised approaches is more and more desirable but, unfortunately, their performances are not still satisfactory and more investigations are required. To this end, this paper proposes a new unsupervised approach to automatically detect the center of the eye: its algorithmic core is a representation of the eye's shape that is obtained through a differential analysis of image intensities and the subsequent combination with the local variability of the appearance represented by self similarity coefficients. The experimental evidence of the effectiveness of the method was demonstrated on challenging databases containing facial images. Moreover, its capabilities to accurately detect the centers of the eyes were also favourably compared with those of the leading state-of-the-art methods. PMID- 25122453 TI - Sorghum phytochrome B inhibits flowering in long days by activating expression of SbPRR37 and SbGHD7, repressors of SbEHD1, SbCN8 and SbCN12. AB - Light signaling by phytochrome B in long days inhibits flowering in sorghum by increasing expression of the long day floral repressors PSEUDORESPONSE REGULATOR PROTEIN (SbPRR37, Ma1) and GRAIN NUMBER, PLANT HEIGHT AND HEADING DATE 7 (SbGHD7, Ma6). SbPRR37 and SbGHD7 RNA abundance peaks in the morning and in the evening of long days through coordinate regulation by light and output from the circadian clock. 58 M, a phytochrome B deficient (phyB-1, ma3R) genotype, flowered ~60 days earlier than 100 M (PHYB, Ma3) in long days and ~11 days earlier in short days. Populations derived from 58 M (Ma1, ma3R, Ma5, ma6) and R.07007 (Ma1, Ma3, ma5, Ma6) varied in flowering time due to QTL aligned to PHYB/phyB-1 (Ma3), Ma5, and GHD7/ghd7-1 (Ma6). PHYC was proposed as a candidate gene for Ma5 based on alignment and allelic variation. PHYB and Ma5 (PHYC) were epistatic to Ma1 and Ma6 and progeny recessive for either gene flowered early in long days. Light signaling mediated by PhyB was required for high expression of the floral repressors SbPRR37 and SbGHD7 during the evening of long days. In 100 M (PHYB) the floral activators SbEHD1, SbCN8 and SbCN12 were repressed in long days and de repressed in short days. In 58 M (phyB-1) these genes were highly expressed in long and short days. Furthermore, SbCN15, the ortholog of rice Hd3a (FT), is expressed at low levels in 100 M but at high levels in 58 M (phyB-1) regardless of day length, indicating that PhyB regulation of SbCN15 expression may modify flowering time in a photoperiod-insensitive manner. PMID- 25122454 TI - Diverse expression of selected SMN complex proteins in humans with sporadic amyotrophic lateral sclerosis and in a transgenic rat model of familial form of the disease. AB - BACKGROUND AND OBJECTIVE: There is circumstantial evidence linking sporadic amyotrophic lateral sclerosis (ALS) cases to a malfunction or deficit of a multimeric SMN complex that scrutinizes cellular RNAs; the core of this complex is survival motor neuron (SMN, or gemin 1) protein. We intended to verify this hypothesis by comparing the expression of both SMN and several other functionally associated gemins in the anterior horn motoneurons of patients who died of sporadic ALS (sALS), of transgenic rats with overexpression of the mutated human superoxide dismutase 1 gene (SOD1(G93A)) that represent a model of familial ALS (fALS), and of the respective controls. METHODS: Using archival material of paraffin blocks with samples of human and rat spinal cords, immunohistochemical reactions with antibodies against SMN and gemins 2, 3, and 4 were performed and assessed by light microscopy. RESULTS: The expression of SMN and all other studied gemins was observed in motoneurons of sALS patients, fALS rats, and in all controls, although the intensity varied. The immunolabeling was most intense in sALS patients with relatively fast disease course, and decreased with increasing disease duration in both the human sALS and rat fALS material. Irrespective of the disease stage, sALS material showed no or very low gemin 2 immunoreactivity, while clear gemin 2 immunoreactivity was observed in all fALS rats and control material. CONCLUSION: The deficient expression of gemin 2 in spinal cord motoneurons in human sALS may lead to a dysfunction and loss of neuroprotective action of the SMN complex. PMID- 25122455 TI - Dynamic mechanisms of neocortical focal seizure onset. AB - Recent experimental and clinical studies have provided diverse insight into the mechanisms of human focal seizure initiation and propagation. Often these findings exist at different scales of observation, and are not reconciled into a common understanding. Here we develop a new, multiscale mathematical model of cortical electric activity with realistic mesoscopic connectivity. Relating the model dynamics to experimental and clinical findings leads us to propose three classes of dynamical mechanisms for the onset of focal seizures in a unified framework. These three classes are: (i) globally induced focal seizures; (ii) globally supported focal seizures; (iii) locally induced focal seizures. Using model simulations we illustrate these onset mechanisms and show how the three classes can be distinguished. Specifically, we find that although all focal seizures typically appear to arise from localised tissue, the mechanisms of onset could be due to either localised processes or processes on a larger spatial scale. We conclude that although focal seizures might have different patient specific aetiologies and electrographic signatures, our model suggests that dynamically they can still be classified in a clinically useful way. Additionally, this novel classification according to the dynamical mechanisms is able to resolve some of the previously conflicting experimental and clinical findings. PMID- 25122456 TI - White blood cell-based detection of asymptomatic scrapie infection by ex vivo assays. AB - Prion transmission can occur by blood transfusion in human variant Creutzfeldt Jakob disease and in experimental animal models, including sheep. Screening of blood and its derivatives for the presence of prions became therefore a major public health issue. As infectious titer in blood is reportedly low, highly sensitive and robust methods are required to detect prions in blood and blood derived products. The objectives of this study were to compare different methods- in vitro, ex vivo and in vivo assays--to detect prion infectivity in cells prepared from blood samples obtained from scrapie infected sheep at different time points of the disease. Protein misfolding cyclic amplification (PMCA) and bioassays in transgenic mice expressing the ovine prion protein were the most efficient methods to identify infected animals at any time of the disease (asymptomatic to terminally-ill stages). However scrapie cell and cerebellar organotypic slice culture assays designed to replicate ovine prions in culture also allowed detection of prion infectivity in blood cells from asymptomatic sheep. These findings confirm that white blood cells are appropriate targets for preclinical detection and introduce ex vivo tools to detect blood infectivity during the asymptomatic stage of the disease. PMID- 25122457 TI - Global decline in suitable habitat for Angiostrongylus ( = Parastrongylus) cantonensis: the role of climate change. AB - Climate change is implicated in the alteration of the ranges of species worldwide. Such shifts in species distributions may introduce parasites/pathogens, hosts, and vectors associated with disease to new areas. The parasite Angiostrongylus ( = Parastrongylus) cantonensis is an invasive species that causes eosinophilic meningitis in humans and neurological abnormalities in domestic/wild animals. Although native to southeastern Asia, A. cantonensis has now been reported from more than 30 countries worldwide. Given the health risks, it is important to describe areas with potentially favorable climate for the establishment of A. cantonensis, as well as areas where this pathogen might become established in the future. We used the program Maxent to develop an ecological niche model for A. cantonensis based on 86 localities obtained from published literature. We then modeled areas of potential A. cantonensis distribution as well as areas projected to have suitable climatic conditions under four Representative Concentration Pathways (RCP) scenarios by the 2050s and the 2070s. The best model contained three bioclimatic variables: mean diurnal temperature range, minimum temperature of coldest month and precipitation of warmest quarter. Potentially suitable habitat for A. cantonensis was located worldwide in tropical and subtropical regions. Under all climate change RCP scenarios, the center of the projected distribution shifted away from the equator at a rate of 68-152 km per decade. However, the extent of areas with highly suitable habitat (>50%) declined by 10.66-15.66% by the 2050s and 13.11-16.11% by the 2070s. These results conflict with previous studies, which have generally found that the prevalence of tropical pathogens will increase during the 21st century. Moreover, it is likely that A. cantonensis will continue to expand its current range in the near future due to introductions and host expansion, whereas climate change will reduce the total geographic area of most suitable climatic conditions during the coming decades. PMID- 25122458 TI - De novo transcriptome assembly and comparative analysis of differentially expressed genes in Prunus dulcis Mill. in response to freezing stress. AB - Almond (Prunus dulcis Mill.), one of the most important nut crops, requires chilling during winter to develop fruiting buds. However, early spring chilling and late spring frost may damage the reproductive tissues leading to reduction in the rate of productivity. Despite the importance of transcriptional changes and regulation, little is known about the almond's transcriptome under the cold stress conditions. In the current research, we used RNA-seq technique to study the response of the reproductive tissues of almond (anther and ovary) to frost stress. RNA sequencing resulted in more than 20 million reads from anther and ovary tissues of almond, individually. About 40,000 contigs were assembled and annotated de novo in each tissue. Profile of gene expression in ovary showed significant alterations in 5,112 genes, whereas in anther 6,926 genes were affected by freezing stress. Around two thousands of these genes were common altered genes in both ovary and anther libraries. Gene ontology indicated the involvement of differentially expressed (DE) genes, responding to freezing stress, in metabolic and cellular processes. qRT-PCR analysis verified the expression pattern of eight genes randomly selected from the DE genes. In conclusion, the almond gene index assembled in this study and the reported DE genes can provide great insights on responses of almond and other Prunus species to abiotic stresses. The obtained results from current research would add to the limited available information on almond and Rosaceae. Besides, the findings would be very useful for comparative studies as the number of DE genes reported here is much higher than that of any previous reports in this plant. PMID- 25122460 TI - Effects of aging on osteogenic response and heterotopic ossification following burn injury in mice. AB - Heterotopic ossification (HO) is a common and debilitating complication of burns, traumatic brain injuries, and musculoskeletal trauma and surgery. Although the exact mechanism of ectopic bone formation is unknown, mesenchymal stem cells (MSCs) capable of osteogenic differentiation are known to play an essential role. Interestingly, the prevalence of HO in the elderly population is low despite the high overall occurrence of musculoskeletal injury and orthopedic procedures. We hypothesized that a lower osteogenicity of MSCs would be associated with blunted HO formation in old compared with young mice. In vitro osteogenic differentiation of adipose-derived MSCs from old (18-20 months) and young (6-8 weeks) C57/BL6 mice was assessed, with or without preceding burn injury. In vivo studies were then performed using an Achilles tenotomy with concurrent burn injury HO model. HO formation was quantified using MUCT scans, Raman spectroscopy, and histology. MSCs from young mice had more in vitro bone formation, upregulation of bone formation pathways, and higher activation of Smad and nuclear factor kappa B (NF kappaB) signaling following burn injury. This effect was absent or blunted in cells from old mice. In young mice, burn injury significantly increased HO formation, NF-kappaB activation, and osteoclast activity at the tenotomy site. This blunted, reactive osteogenic response in old mice follows trends seen clinically and may be related to differences in the ability to mount acute inflammatory responses. This unique characterization of HO and MSC osteogenic differentiation following inflammatory insult establishes differences between age populations and suggests potential pathways that could be targeted in the future with therapeutics. PMID- 25122461 TI - Prion propagation can occur in a prokaryote and requires the ClpB chaperone. AB - Prions are self-propagating protein aggregates that are characteristically transmissible. In mammals, the PrP protein can form a prion that causes the fatal transmissible spongiform encephalopathies. Prions have also been uncovered in fungi, where they act as heritable, protein-based genetic elements. We previously showed that the yeast prion protein Sup35 can access the prion conformation in Escherichia coli. Here, we demonstrate that E. coli can propagate the Sup35 prion under conditions that do not permit its de novo formation. Furthermore, we show that propagation requires the disaggregase activity of the ClpB chaperone. Prion propagation in yeast requires Hsp104 (a ClpB ortholog), and prior studies have come to conflicting conclusions about ClpB's ability to participate in this process. Our demonstration of ClpB-dependent prion propagation in E. coli suggests that the cytoplasmic milieu in general and a molecular machine in particular are poised to support protein-based heredity in the bacterial domain of life. PMID- 25122463 TI - RLIMS-P: an online text-mining tool for literature-based extraction of protein phosphorylation information. AB - Protein phosphorylation is central to the regulation of most aspects of cell function. Given its importance, it has been the subject of active research as well as the focus of curation in several biological databases. We have developed Rule-based Literature Mining System for protein Phosphorylation (RLIMS-P), an online text-mining tool to help curators identify biomedical research articles relevant to protein phosphorylation. The tool presents information on protein kinases, substrates and phosphorylation sites automatically extracted from the biomedical literature. The utility of the RLIMS-P Web site has been evaluated by curators from Phospho.ELM, PhosphoGRID/BioGrid and Protein Ontology as part of the BioCreative IV user interactive task (IAT). The system achieved F-scores of 0.76, 0.88 and 0.92 for the extraction of kinase, substrate and phosphorylation sites, respectively, and a precision of 0.88 in the retrieval of relevant phosphorylation literature. The system also received highly favorable feedback from the curators in a user survey. Based on the curators' suggestions, the Web site has been enhanced to improve its usability. In the RLIMS-P Web site, phosphorylation information can be retrieved by PubMed IDs or keywords, with an option for selecting targeted species. The result page displays a sortable table with phosphorylation information. The text evidence page displays the abstract with color-coded entity mentions and includes links to UniProtKB entries via normalization, i.e., the linking of entity mentions to database identifiers, facilitated by the GenNorm tool and by the links to the bibliography in UniProt. Log in and editing capabilities are offered to any user interested in contributing to the validation of RLIMS-P results. Retrieved phosphorylation information can also be downloaded in CSV format and the text evidence in the BioC format. RLIMS-P is freely available. DATABASE URL: http://www.proteininformationresource.org/rlimsp/ PMID- 25122465 TI - Development of the Cell Population in the Brain White Matter of Young Children. AB - While brain gray matter is primarily associated with sensorimotor processing and cognition, white matter modulates the distribution of action potentials, coordinates communication between different brain regions, and acts as a relay for input/output signals. Previous studies have described morphological changes in gray and white matter during childhood and adolescence, which are consistent with cellular genesis and maturation, but corresponding events in infants are poorly documented. In the present study, we estimated the total number of cells (neurons, oligodendrocytes, astrocytes, and microglia) in the cerebral white matter of 9 infants aged 0-33 months, using design-based stereological methods to obtain quantitative data about brain development. There were linear increases with age in the numbers of oligodendrocytes (7-28 billion) and astrocytes (1.5 6.7 billion) during the first 3 years of life, thus attaining two-thirds of the corresponding numbers in adults. The numbers of neurons (0.7 billion) and microglia (0.2 billion) in the white matter did not increase during the first 3 years of life, but showed large biological variation. PMID- 25122462 TI - Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits. AB - Epsin is an evolutionarily conserved endocytic clathrin adaptor whose most critical function(s) in clathrin coat dynamics remain(s) elusive. To elucidate such function(s), we generated embryonic fibroblasts from conditional epsin triple KO mice. Triple KO cells displayed a dramatic cell division defect. Additionally, a robust impairment in clathrin-mediated endocytosis was observed, with an accumulation of early and U-shaped pits. This defect correlated with a perturbation of the coupling between the clathrin coat and the actin cytoskeleton, which we confirmed in a cell-free assay of endocytosis. Our results indicate that a key evolutionary conserved function of epsin, in addition to other roles that include, as we show here, a low affinity interaction with SNAREs, is to help generate the force that leads to invagination and then fission of clathrin-coated pits. PMID- 25122464 TI - Lower intensified target LDL-c level of statin therapy results in a higher risk of incident diabetes: a meta-analysis. AB - BACKGROUND: A recent meta-analysis has reported that intensive-dose statin drug increases the risk of incident diabetes. However, doubling of the statin dose generates only a further 6% decrease in low-density lipoprotein cholesterol (LDL c) on average. This study aimed to determine whether statin therapy with lower intensive-target LDL-c level contributes to higher risk of new-onset diabetes. METHODS: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled endpoint trials of statins conducted from 1966 to 2012. We included trials with more than 1000 participants who were followed up for at least 2 years. The included trials were stratified by the target LDL-c level. I2 statistic was used to measure heterogeneity between trials. We further calculated risk estimates with random-effect meta-analysis. Meta-regression was used to identify the potential risk factors of statin-induced diabetes. RESULTS: Fourteen trials with a total of 95 102 non-diabetic participants were included. The risks elevated by 33% [odds ratio (OR) = 1.33; 95% confidence interval (CI) 1.14-1.56; I(2) = 7.7%] and 16% (OR = 1.16; 95% CI 1.06-1.28; I(2)= 0.0%) when the intensified target LDL-c levels were <= 1.8 mmol/L and 1.8-2.59 mmol/L, respectively. The risk of incident diabetes did not increase when the target LDL-c level was >= 2.59 mmol/L. Apart from age, female, and baseline level of total cholesterol, meta-regression analysis showed that the target and baseline levels of LDL-c and relative LDL-c reduction were predictors of statin-induced diabetes. CONCLUSION: A lower intensified target LDL-c level of statin therapy resulted in a higher risk of incident diabetes. PMID- 25122466 TI - The Fault Lies on the Other Side: Altered Brain Functional Connectivity in Psychiatric Disorders is Mainly Caused by Counterpart Regions in the Opposite Hemisphere. AB - Many psychiatric disorders are associated with abnormal resting-state functional connectivity between pairs of brain regions, although it remains unclear whether the fault resides within the pair of regions themselves or other regions connected to them. Identifying the source of dysfunction is crucial for understanding the etiology of different disorders. Using pathway- and network based techniques to analyze resting-state functional magnetic imaging data from a large population of patients with attention deficit hyperactivity disorder (239 patients, 251 controls), major depression (39 patients, 37 controls), and schizophrenia (69 patients, 62 controls), we show for the first time that only network-based cross-correlation identifies significant functional connectivity changes in all 3 disorders which survive correction. This demonstrates that the primary source of dysfunction resides not in the regional pairs themselves but in their external connections. Combining pathway and network-based functional connectivity analysis, we established that, in all 3 disorders, the counterparts of pairs of regions in the opposite hemisphere contribute 60-76% to altered functional connectivity, compared with only 17-21% from the regions themselves. Thus, a transdiagnostic feature is of abnormal functional connectivity between brain regions produced via their contralateral counterparts. Our results demonstrate an important role for contralateral counterpart regions in contributing to altered regional connectivity in psychiatric disorders. PMID- 25122467 TI - Common myna roosts are not recruitment centres. AB - We studied communal roosting in the Common Myna (Acridotheres tristis) in the light of the recruitment centre hypothesis and predation at the roost. The number and sizes of flocks departing from and arriving at focal roosts were recorded over a two year period. We also recorded the sizes and behaviour of foraging flocks. We found that flock sizes of birds departing from roosts at sunrise were larger than those at the feeding site, suggesting that there was no recruitment from the roosts. Flocks entering the roosts during sunset were larger on average than those leaving the following sunrise, suggesting no consolidation of flocks in the morning. Flocks entering the roosts at sunset were also larger on average than those that had left that sunrise, although there was no recruitment at the feeding site. There was no effect of group size on the proportion of time spent feeding. Contrary to expectation, single birds showed lower apparent vigilance than birds that foraged in pairs or groups, possibly due to scrounging tactics being used in the presence of feeding companions. Thus, the recruitment centre hypothesis did not hold in our study population of mynas. Predation at dawn and dusk were also not important to communal roosting: predators near the roosts did not result in larger flocks, and resulted in larger durations of arrival/departure contrary to expectation. Since flock sizes were smallest at the feeding site and larger in the evening than in the morning, but did not coincide with predator activity, information transfer unrelated to food (such as breeding opportunities) may possibly give rise to the evening aggregations. PMID- 25122468 TI - Education on hygiene and sanitation is the need of the hour in India. PMID- 25122469 TI - Effects of a post-deworming health hygiene education intervention on absenteeism in school-age children of the Peruvian Amazon. AB - Soil-transmitted helminth (STH) infections are a leading cause of disability and disease burden in school-age children of worm-endemic regions. Their effect on school absenteeism, however, remains unclear. The World Health Organization currently recommends delivering mass deworming and health hygiene education through school-based programs, in an effort to control STH-related morbidity. In this cluster-RCT, the impact of a health hygiene education intervention on absenteeism was measured. From April to June 2010, all Grade 5 students at 18 schools in a worm-endemic region of the Peruvian Amazon were dewormed. Immediately following deworming, nine schools were randomly assigned to the intervention arm of the trial using a matched-pair design. The Grade 5 students attending intervention schools (N = 517) received four months of health hygiene education aimed at increasing knowledge of STH prevention. Grade 5 students from the other nine schools (N = 571) served as controls. Absenteeism was measured daily through teachers' attendance logs. After four months of follow-up, overall absenteeism rates at intervention and control schools were not statistically significantly different. However, post-trial non-randomized analyses have shown that students with moderate-to-heavy Ascaris infections and light hookworm infections four months after deworming had, respectively, missed 2.4% (95% CI: 0.1%, 4.7%) and 4.6% (95% CI: 1.9%, 7.4%) more schooldays during the follow-up period than their uninfected counterparts. These results provide empirical evidence of a direct effect of STH infections on absenteeism in school-age children. PMID- 25122470 TI - Identification of suitable reference genes for gene expression studies of shoulder instability. AB - Shoulder instability is a common shoulder injury, and patients present with plastic deformation of the glenohumeral capsule. Gene expression analysis may be a useful tool for increasing the general understanding of capsule deformation, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) has become an effective method for such studies. Although RT-qPCR is highly sensitive and specific, it requires the use of suitable reference genes for data normalization to guarantee meaningful and reproducible results. In the present study, we evaluated the suitability of a set of reference genes using samples from the glenohumeral capsules of individuals with and without shoulder instability. We analyzed the expression of six commonly used reference genes (ACTB, B2M, GAPDH, HPRT1, TBP and TFRC) in the antero-inferior, antero-superior and posterior portions of the glenohumeral capsules of cases and controls. The stability of the candidate reference gene expression was determined using four software packages: NormFinder, geNorm, BestKeeper and DataAssist. Overall, HPRT1 was the best single reference gene, and HPRT1 and B2M composed the best pair of reference genes from different analysis groups, including simultaneous analysis of all tissue samples. GenEx software was used to identify the optimal number of reference genes to be used for normalization and demonstrated that the accumulated standard deviation resulting from the use of 2 reference genes was similar to that resulting from the use of 3 or more reference genes. To identify the optimal combination of reference genes, we evaluated the expression of COL1A1. Although the use of different reference gene combinations yielded variable normalized quantities, the relative quantities within sample groups were similar and confirmed that no obvious differences were observed when using 2, 3 or 4 reference genes. Consequently, the use of 2 stable reference genes for normalization, especially HPRT1 and B2M, is a reliable method for evaluating gene expression by RT-qPCR. PMID- 25122471 TI - EVM005: an ectromelia-encoded protein with dual roles in NF-kappaB inhibition and virulence. AB - Poxviruses contain large dsDNA genomes encoding numerous open reading frames that manipulate cellular signalling pathways and interfere with the host immune response. The NF-kappaB signalling cascade is an important mediator of innate immunity and inflammation, and is tightly regulated by ubiquitination at several key points. A critical step in NF-kappaB activation is the ubiquitination and degradation of the inhibitor of kappaB (IkappaBalpha), by the cellular SCFbeta TRCP ubiquitin ligase complex. We show here that upon stimulation with TNFalpha or IL-1beta, Orthopoxvirus-infected cells displayed an accumulation of phosphorylated IkappaBalpha, indicating that NF-kappaB activation was inhibited during poxvirus infection. Ectromelia virus is the causative agent of lethal mousepox, a natural disease that is fatal in mice. Previously, we identified a family of four ectromelia virus genes (EVM002, EVM005, EVM154 and EVM165) that contain N-terminal ankyrin repeats and C-terminal F-box domains that interact with the cellular SCF ubiquitin ligase complex. Since degradation of IkappaBalpha is catalyzed by the SCFbeta-TRCP ubiquitin ligase, we investigated the role of the ectromelia virus ankyrin/F-box protein, EVM005, in the regulation of NF kappaB. Expression of Flag-EVM005 inhibited both TNFalpha- and IL-1beta stimulated IkappaBalpha degradation and p65 nuclear translocation. Inhibition of the NF-kappaB pathway by EVM005 was dependent on the F-box domain, and interaction with the SCF complex. Additionally, ectromelia virus devoid of EVM005 was shown to inhibit NF-kappaB activation, despite lacking the EVM005 open reading frame. Finally, ectromelia virus devoid of EVM005 was attenuated in both A/NCR and C57BL/6 mouse models, indicating that EVM005 is required for virulence and immune regulation in vivo. PMID- 25122473 TI - The impact of herbicide-resistant rice technology on phenotypic diversity and population structure of United States weedy rice. AB - The use of herbicide-resistant (HR) Clearfield rice (Oryza sativa) to control weedy rice has increased in the past 12 years to constitute about 60% of rice acreage in Arkansas, where most U.S. rice is grown. To assess the impact of HR cultivated rice on the herbicide resistance and population structure of weedy rice, weedy samples were collected from commercial fields with a history of Clearfield rice. Panicles from each weedy type were harvested and tested for resistance to imazethapyr. The majority of plants sampled had at least 20% resistant offspring. These resistant weeds were 97 to 199 cm tall and initiated flowering from 78 to 128 d, generally later than recorded for accessions collected prior to the widespread use of Clearfield rice (i.e. historical accessions). Whereas the majority (70%) of historical accessions had straw colored hulls, only 30% of contemporary HR weedy rice had straw-colored hulls. Analysis of genotyping-by-sequencing data showed that HR weeds were not genetically structured according to hull color, whereas historical weedy rice was separated into straw-hull and black-hull populations. A significant portion of the local rice crop genome was introgressed into HR weedy rice, which was rare in historical weedy accessions. Admixture analyses showed that HR weeds tend to possess crop haplotypes in the portion of chromosome 2 containing the ACETOLACTATE SYNTHASE gene, which confers herbicide resistance to Clearfield rice. Thus, U.S. HR weedy rice is a distinct population relative to historical weedy rice and shows modifications in morphology and phenology that are relevant to weed management. PMID- 25122474 TI - Multiple sclerosis: progression rate and severity in a multicenter cohort from Algeria. PMID- 25122472 TI - Label-free protein quantification for plant Golgi protein localization and abundance. AB - The proteomic composition of the Arabidopsis (Arabidopsis thaliana) Golgi apparatus is currently reasonably well documented; however, little is known about the relative abundances between different proteins within this compartment. Accurate quantitative information of Golgi resident proteins is of great importance: it facilitates a better understanding of the biochemical processes that take place within this organelle, especially those of different polysaccharide synthesis pathways. Golgi resident proteins are challenging to quantify because the abundance of this organelle is relatively low within the cell. In this study, an organelle fractionation approach targeting the Golgi apparatus was combined with a label-free quantitative mass spectrometry (data independent acquisition method using ion mobility separation known as LC-IMS MS(E) [or HDMS(E)]) to simultaneously localize proteins to the Golgi apparatus and assess their relative quantity. In total, 102 Golgi-localized proteins were quantified. These data show that organelle fractionation in conjunction with label-free quantitative mass spectrometry is a powerful and relatively simple tool to access protein organelle localization and their relative abundances. The findings presented open a unique view on the organization of the plant Golgi apparatus, leading toward unique hypotheses centered on the biochemical processes of this organelle. PMID- 25122475 TI - The central role of mitochondria in axonal degeneration in multiple sclerosis. AB - Neurodegeneration in multiple sclerosis (MS) is related to inflammation and demyelination. In acute MS lesions and experimental autoimmune encephalomyelitis focal immune attacks damage axons by injuring axonal mitochondria. In progressive MS, however, axonal damage occurs in chronically demyelinated regions, myelinated regions and also at the active edge of slowly expanding chronic lesions. How axonal energy failure occurs in progressive MS is incompletely understood. Recent studies show that oligodendrocytes supply lactate to myelinated axons as a metabolic substrate for mitochondria to generate ATP, a process which will be altered upon demyelination. In addition, a number of studies have identified mitochondrial abnormalities within neuronal cell bodies in progressive MS, leading to a deficiency of mitochondrial respiratory chain complexes or enzymes. Here, we summarise the mitochondrial abnormalities evident within neurons and discuss how these grey matter mitochondrial abnormalities may increase the vulnerability of axons to degeneration in progressive MS. Although neuronal mitochondrial abnormalities will culminate in axonal degeneration, understanding the different contributions of mitochondria to the degeneration of myelinated and demyelinated axons is an important step towards identifying potential therapeutic targets for progressive MS. PMID- 25122476 TI - Non-random escape pathways from a broadly neutralizing human monoclonal antibody map to a highly conserved region on the hepatitis C virus E2 glycoprotein encompassing amino acids 412-423. AB - A challenge for hepatitis C virus (HCV) vaccine development is to define epitopes that are able to elicit protective antibodies against this highly diverse virus. The E2 glycoprotein region located at residues 412-423 is conserved and antibodies to 412-423 have broadly neutralizing activities. However, an adaptive mutation, N417S, is associated with a glycan shift in a variant that cannot be neutralized by a murine but by human monoclonal antibodies (HMAbs) against 412 423. To determine whether HCV escapes from these antibodies, we analyzed variants that emerged when cell culture infectious HCV virions (HCVcc) were passaged under increasing concentrations of a specific HMAb, HC33.1. Multiple nonrandom escape pathways were identified. Two pathways occurred in the context of an N-glycan shift mutation at N417T. At low antibody concentrations, substitutions of two residues outside of the epitope, N434D and K610R, led to variants having improved in vitro viral fitness and reduced sensitivity to HC33.1 binding and neutralization. At moderate concentrations, a S419N mutation occurred within 412 423 in escape variants that have greatly reduced sensitivity to HC33.1 but compromised viral fitness. Importantly, the variants generated from these pathways differed in their stability. N434D and K610R-associated variants were stable and became dominant as the virions were passaged. The S419N mutation reverted back to N419S when immune pressure was reduced by removing HC33.1. At high antibody concentrations, a mutation at L413I was observed in variants that were resistant to HC33.1 neutralization. Collectively, the combination of multiple escape pathways enabled the virus to persist under a wide range of antibody concentrations. Moreover, these findings pose a different challenge to vaccine development beyond the identification of highly conserved epitopes. It will be necessary for a vaccine to induce high potency antibodies that prevent the formation of escape variants, which can co-exist with lower potency or levels of neutralizing activities. PMID- 25122477 TI - Surface physicochemistry and ionic strength affects eDNA's role in bacterial adhesion to abiotic surfaces. AB - Extracellular DNA (eDNA) is an important structural component of biofilms formed by many bacteria, but few reports have focused on its role in initial cell adhesion. The aim of this study was to investigate the role of eDNA in bacterial adhesion to abiotic surfaces, and determine to which extent eDNA-mediated adhesion depends on the physicochemical properties of the surface and surrounding liquid. We investigated eDNA alteration of cell surface hydrophobicity and zeta potential, and subsequently quantified the effect of eDNA on the adhesion of Staphylococcus xylosus to glass surfaces functionalised with different chemistries resulting in variable hydrophobicity and charge. Cell adhesion experiments were carried out at three different ionic strengths. Removal of eDNA from S. xylosus cells by DNase treatment did not alter the zeta potential, but rendered the cells more hydrophilic. DNase treatment impaired adhesion of cells to glass surfaces, but the adhesive properties of S. xylosus were regained within 30 minutes if DNase was not continuously present, implying a continuous release of eDNA in the culture. Removal of eDNA lowered the adhesion of S. xylosus to all surfaces chemistries tested, but not at all ionic strengths. No effect was seen on glass surfaces and carboxyl-functionalised surfaces at high ionic strength, and a reverse effect occurred on amine-functionalised surfaces at low ionic strength. However, eDNA promoted adhesion of cells to hydrophobic surfaces irrespective of the ionic strength. The adhesive properties of eDNA in mediating initial adhesion of S. xylosus is thus highly versatile, but also dependent on the physicochemical properties of the surface and ionic strength of the surrounding medium. PMID- 25122480 TI - Attorneys general from 29 US states urge tougher e-cigarette regulations. PMID- 25122479 TI - Optimal behavioral hierarchy. AB - Human behavior has long been recognized to display hierarchical structure: actions fit together into subtasks, which cohere into extended goal-directed activities. Arranging actions hierarchically has well established benefits, allowing behaviors to be represented efficiently by the brain, and allowing solutions to new tasks to be discovered easily. However, these payoffs depend on the particular way in which actions are organized into a hierarchy, the specific way in which tasks are carved up into subtasks. We provide a mathematical account for what makes some hierarchies better than others, an account that allows an optimal hierarchy to be identified for any set of tasks. We then present results from four behavioral experiments, suggesting that human learners spontaneously discover optimal action hierarchies. PMID- 25122478 TI - Epidermal growth factor stimulates nuclear factor-kappaB activation and heme oxygenase-1 expression via c-Src, NADPH oxidase, PI3K, and Akt in human colon cancer cells. AB - Previous report showed that epidermal growth factor (EGF) promotes tumor progression. Several studies demonstrated that growth factors can induce heme oxygenase (HO)-1 expression, protect against cellular injury and cancer cell proliferation. In this study, we investigated the involvement of the c-Src, NADPH oxidase, reactive oxygen species (ROS), PI3K/Akt, and NF-kappaB signaling pathways in EGF-induced HO-1 expression in human HT-29 colon cancer cells. Treatment of HT-29 cells with EGF caused HO-1 to be expressed in concentration- and time-dependent manners. Treatment of HT-29 cells with AG1478 (an EGF receptor (EGFR) inhibitor), small interfering RNA of EGFR (EGFR siRNA), a dominant negative mutant of c-Src (c-Src DN), DPI (an NADPH oxidase inhibitor), glutathione (an ROS inhibitor), LY294002 (a PI3K inhibitor), and an Akt DN inhibited EGF-induced HO-1 expression. Stimulation of cells with EGF caused an increase in c-Src phosphorylation at Tyr406 in a time-dependent manner. Treatment of HT-29 cells with EGF induced an increase in p47(phox) translocation from the cytosol to membranes. The EGF-induced ROS production was inhibited by DPI. Stimulation of cells with EGF resulted in an increase in Akt phosphorylation at Ser473, which was inhibited by c-Src DN, DPI, and LY 294002. Moreover, treatment of HT-29 cells with a dominant negative mutant of IkappaB (IkappaBalphaM) inhibited EGF-induced HO-1 expression. Stimulation of cells with EGF induced p65 translocation from the cytosol to nuclei. Treatment of HT-29 cells with EGF induced an increase in kappaB-luciferase activity, which was inhibited by a c-Src DN, LY 294002, and an Akt DN. Furthermore, EGF-induced colon cancer cell proliferation was inhibited by Sn(IV)protoporphyrin-IX (snPP, an HO-1 inhibitor). Taken together, these results suggest that the c-Src, NADPH oxidase, PI3K, and Akt signaling pathways play important roles in EGF-induced NF-kappaB activation and HO-1 expression in HT-29 cells. Moreover, overexpression of HO-1 mediates EGF induced colon cancer cell proliferation. PMID- 25122481 TI - Interactions of Rice tungro bacilliform pararetrovirus and its protein P4 with plant RNA-silencing machinery. AB - Small interfering RNA (siRNA)-directed gene silencing plays a major role in antiviral defense. Virus-derived siRNAs inhibit viral replication in infected cells and potentially move to neighboring cells, immunizing them from incoming virus. Viruses have evolved various ways to evade and suppress siRNA production or action. Here, we show that 21-, 22-, and 24-nucleotide (nt) viral siRNAs together constitute up to 19% of total small RNA population of Oryza sativa plants infected with Rice tungro bacilliform virus (RTBV) and cover both strands of the RTBV DNA genome. However, viral siRNA hotspots are restricted to a short noncoding region between transcription and reverse-transcription start sites. This region generates double-stranded RNA (dsRNA) precursors of siRNAs and, in pregenomic RNA, forms a stable secondary structure likely inaccessible to siRNA directed cleavage. In transient assays, RTBV protein P4 suppressed cell-to-cell spread of silencing but enhanced cell-autonomous silencing, which correlated with reduced 21-nt siRNA levels and increased 22-nt siRNA levels. Our findings imply that RTBV generates decoy dsRNA that restricts siRNA production to the structured noncoding region and thereby protects other regions of the viral genome from repressive action of siRNAs, while the viral protein P4 interferes with cell-to cell spread of antiviral silencing. PMID- 25122482 TI - The novel monocot-specific 9-lipoxygenase ZmLOX12 is required to mount an effective jasmonate-mediated defense against Fusarium verticillioides in maize. AB - Fusarium verticillioides is a major limiting factor for maize production due to ear and stalk rot and the contamination of seed with the carcinogenic mycotoxin fumonisin. While lipoxygenase (LOX)-derived oxylipins have been implicated in defense against diverse pathogens, their function in maize resistance against F. verticillioides is poorly understood. Here, we functionally characterized a novel maize 9-LOX gene, ZmLOX12. This gene is distantly related to known dicot LOX genes, with closest homologs found exclusively in other monocot species. ZmLOX12 is predominantly expressed in mesocotyls in which it is strongly induced in response to F. verticillioides infection. The Mutator transposon-insertional lox12-1 mutant is more susceptible to F. verticillioides colonization of mesocotyls, stalks, and kernels. The infected mutant kernels accumulate a significantly greater amount of the mycotoxin fumonisin. Reduced resistance to the pathogen is accompanied by diminished levels of the jasmonic acid (JA) precursor 12-oxo phytodienoic acid, JA-isoleucine, and expression of jasmonate biosynthetic genes. Supporting the strong defense role of jasmonates, the JA deficient opr7 opr8 double mutant displayed complete lack of immunity to F. verticillioides. Unexpectedly, the more susceptible lox12 mutant accumulated higher levels of kauralexins, suggesting that F. verticillioides is tolerant to this group of antimicrobial phytoalexins. This study demonstrates that this unique monocot-specific 9-LOX plays a key role in defense against F. verticillioides in diverse maize tissues and provides genetic evidence that JA is the major defense hormone against this pathogen. PMID- 25122483 TI - Nucleoporin 75 is involved in the ethylene-mediated production of phytoalexin for the resistance of Nicotiana benthamiana to Phytophthora infestans. AB - Mature Nicotiana benthamiana shows stable resistance to the oomycete pathogen Phytophthora infestans. Induction of phytoalexin (capsidiol) production is essential for the resistance, which is upregulated via a mitogen-activated protein kinase (MAPK) cascade (NbMEK2-WIPK/SIPK) followed by ethylene signaling. In this study, NbNup75 (encodes a nuclear pore protein Nucleoporin75) was identified as an essential gene for resistance of N. benthamiana to P. infestans. In NbNup75-silenced plants, initial events of elicitor-induced responses such as phosphorylation of MAPK and expression of defense-related genes were not affected, whereas induction of later defense responses such as capsidiol production and cell death induction was suppressed or delayed. Ethylene production induced by either INF1 or NbMEK2 was reduced in NbNup75-silenced plants, whereas the expression of NbEAS (a gene for capsidiol biosynthesis) induced by ethylene was not affected, indicating that Nup75 is required for the induction of ethylene production but not for ethylene signaling. Given that nuclear accumulation of polyA RNA was increased in NbNup75-silenced plants, efficient export of mRNA from nuclei via nuclear pores would be important for the timely upregulation of defense responses. Collectively, Nup75 is involved in the induction of a later stage of defense responses, including the ethylene-mediated production of phytoalexin for the resistance of N. benthamiana to P. infestans. PMID- 25122484 TI - Endoscopic balloon dilatation as an effective treatment for lower and upper benign gastrointestinal system anastomotic stenosis. AB - OBJECTIVE: Endoscopic balloon dilatation (EBD) is currently accepted as an effective, safe, and first-line treatment of postoperative benign gastrointestinal anastomosis stenosis (BGAS); however, a limited number of publications on the subject exist in the literature. The aim of the study was to retrospectively evaluate the efficiency of endoscopic dilatation in patients with postoperative intestinal anastomotic stenoses at a single surgical center. METHODS: Patients with postoperative BGAS treated by EBD at our institution from February 2008 to 2012 were included. The dilatations were all performed using through-the-scope balloons. The balloon was introduced into the stricture using a guidewire under radiologic guidance. Each dilatation session consisted of 2 to 3 two-minute multistep inflations of the balloon until adequate dilatation was achieved. RESULTS: Of the 48 patients included in the study, 44 patients (91.7%) fully recovered and 4 (8.3%) did not respond to treatment. The mean follow-up period was 24 months (range, 3 to 57 mo). Four patients who did not respond to the procedure were treated surgically. Two patients (4.1%) with intestinal perforation during EBD were treated conservatively with a stent. CONCLUSIONS: EBD has a low rate of complications and a high success rate, is well tolerated, and avoids further surgical procedures for BGAS. Therefore, EBD should be the first choice of treatment for postoperative anastomotic stenoses. PMID- 25122485 TI - Totally laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy for choledochal cyst in adults: a single-institute experience of 5 years. AB - PURPOSE: The present study aimed to describe the authors' experience and the intermediate-term outcome for totally laparoscopic choledochal cyst excision and Roux-en-Y hepatoenterostomy at a single center in a 5-year period. METHODS: We retrospectively analyzed the clinical data of totally laparoscopic choledochal cyst excision and Roux-en-Y hepatoenterostomy on 31 adult patients from January 2009 to November 2013. RESULTS: Thirty-one cases successfully underwent totally laparoscopic choledochal cyst excision laparoscopy and Roux-en-Y hepatoenterostomy. The operation time varied from 200 to 360 minutes. The intraoperative blood loss was 50 to 210 mL. The patients passed flatus in 3.0 +/- 1.3 days. The mean time interval to resume oral intake from the time of surgery was 3.8 +/- 1.4 days. The duration of postoperative intravenous fluids was 4 to 11 days. Postoperative ambulation varied from 2 to 4 days. The duration of hospital stay was 4 to 13 days. Follow-up observations lasted 3 to 59 months and complications were noted in 4 patients. Of these patients, 1 patient suffered postoperative respiratory tract infection, 1 patient had an episode of adhesive small bowel obstruction, biliary leakage occurred in 1 patient, and 1 patient developed an anastomotic stoma stricture and cholangitis. There were no perioperative deaths. CONCLUSIONS: Totally laparoscopic cyst excision and Roux-en Y hepaticojejunostomy is a safe, efficacious, and minimally invasive procedure for the most instances of adult choledochal cyst. The key of success is skilled laparoscopic skills, good team cooperation, and stapler anastomosis. PMID- 25122488 TI - Extended phase-correlated rescanning irradiation to improve dose homogeneity in carbon-ion beam liver treatment. AB - We previously reported that an adequate number of simple layered phase-correlated rescanning (PCR) irradiations improve dose conformation to a moving target. However, if PCR is not completed within a single gating window due to the particular irradiation specifications selected in advance and/or layer size, the iso-energy layer is completed using next gating window, and the effect of rescanning is effectively nullified. To solve this problem, we developed extended PCR irradiation. Extended PCR is conceptually based on simple PCR. It differs in that the dose rate is adjusted to irradiate the number of rescans within multiple gating windows when simple PCR is not finished within a single gating window. This process is repeated until the total prescribed dose is given. Here, 4DCT imaging was performed under free-breathing conditions in 10 patients with hepatocellular carcinoma. 4D dose distributions for a single field approach were performed with simple PCR and extended PCR using 4DCT. A total dose of 11.25 Gy(RBE) was administered to the field-specific target volume. The number of rescans was changed from 1 to 10. Respiratory gating of a 30% duty cycle around exhalation was applied. Dose assessment metrics (CTV-D95, CTV-Dmin, CTV-Dmax) with PCR improved with an increasing number of rescans, and largely plateaued at five or more rescans. Minimum D95 and Dmin values, and maximum Dmax and HI values fluctuated at odd and even numbers of rescans. Extended PCR improved all dose assessment metrics whereas PCR did not. Values with extended PCR were mostly constant with three or more rescans, or in other words independent of the number of rescans. Extended PCR improved dose conformation to a moving target with greater efficacy than simple PCR when more than two gating windows were necessary. Extended PCR can be applied to irradiation machines having a low maximum dose rate. PMID- 25122487 TI - Global gene expression profiling in three tumor cell lines subjected to experimental cycling and chronic hypoxia. AB - Hypoxia is one of the most important features of the tumor microenvironment, exerting an adverse effect on tumor aggressiveness and patient prognosis. Two types of hypoxia may occur within the tumor mass, chronic (prolonged) and cycling (transient, intermittent) hypoxia. Cycling hypoxia has been shown to induce aggressive tumor cell phenotype and radioresistance more significantly than chronic hypoxia, though little is known about the molecular mechanisms underlying this phenomenon. The aim of this study was to delineate the molecular response to both types of hypoxia induced experimentally in tumor cells, with a focus on cycling hypoxia. We analyzed in vitro gene expression profile in three human cancer cell lines (melanoma, ovarian cancer, and prostate cancer) exposed to experimental chronic or transient hypoxia conditions. As expected, the cell-type specific variability in response to hypoxia was significant. However, the expression of 240 probe sets was altered in all 3 cell lines. We found that gene expression profiles induced by both types of hypoxia were qualitatively similar and strongly depend on the cell type. Cycling hypoxia altered the expression of fewer genes than chronic hypoxia (6,132 vs. 8,635 probe sets, FDR adjusted p<0.05), and with lower fold changes. However, the expression of some of these genes was significantly more affected by cycling hypoxia than by prolonged hypoxia, such as IL8, PLAU, and epidermal growth factor (EGF) pathway-related genes (AREG, HBEGF, and EPHA2). These transcripts were, in most cases, validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our results indicate that experimental cycling hypoxia exerts similar, although less intense effects, on the examined cancer cell lines than its chronic counterpart. Nonetheless, we identified genes and molecular pathways that seem to be preferentially regulated by cyclic hypoxia. PMID- 25122489 TI - A commentary on the disparate perspectives of clinical microbiologists and surgeons: ad hoc antimicrobial use. AB - Prosthetic joints and other orthopedic implants have improved quality of life for patients world-wide and the use of such devices is increasing. However, while infection rates subsequent to associated surgery are relatively low (<3%), the consequences of incidence are considerable, encompassing morbidity (including amputation) and mortality in addition to significant social and economic costs. Emphasis, therefore, has been placed on mitigating microbial risk, with clinical microbiologists and surgeons utilizing rapidly evolving molecular laboratory techniques in detection and diagnosis of infection, which still occurs despite sophisticated patient management. Multidisciplinary approaches are regularly adopted to achieve this. In this commentary, we describe an unusual case of Actinomyces infection in total hip arthroplasty and, in that context, describe the perspectives of the clinical microbiology and surgical teams and how they contrasted. More specifically, this case demonstrates an ad hoc approach to structured eradication of biofilms and intracellular bacteria related to biomaterials, as reflected in early usage of linezolid. This is a complex topic and, as described in this case, such accelerated treatment can be effective. This commentary focuses on the merits of such inadvisable use of potent antimicrobials amid the risk of diminishing valuable antimicrobial efficacy, albeit resulting in desirable patient outcomes. PMID- 25122490 TI - Human NR5A1/SF-1 mutations show decreased activity on BDNF (brain-derived neurotrophic factor), an important regulator of energy balance: testing impact of novel SF-1 mutations beyond steroidogenesis. AB - CONTEXT: Human NR5A1/SF-1 mutations cause 46,XY disorder of sex development (DSD) with broad phenotypic variability, and rarely cause adrenal insufficiency although SF-1 is an important transcription factor for many genes involved in steroidogenesis. In addition, the Sf-1 knockout mouse develops obesity with age. Obesity might be mediated through Sf-1 regulating activity of brain-derived neurotrophic factor (BDNF), an important regulator of energy balance in the ventromedial hypothalamus. OBJECTIVE: To characterize novel SF-1 gene variants in 4 families, clinical, genetic and functional studies were performed with respect to steroidogenesis and energy balance. PATIENTS: 5 patients with 46,XY DSD were found to harbor NR5A1/SF-1 mutations including 2 novel variations. One patient harboring a novel mutation also suffered from adrenal insufficiency. METHODS: SF 1 mutations were studied in cell systems (HEK293, JEG3) for impact on transcription of genes involved in steroidogenesis (CYP11A1, CYP17A1, HSD3B2) and in energy balance (BDNF). BDNF regulation by SF-1 was studied by promoter assays (JEG3). RESULTS: Two novel NR5A1/SF-1 mutations (Glu7Stop, His408Profs*159) were confirmed. Glu7Stop is the 4th reported SF-1 mutation causing DSD and adrenal insufficiency. In vitro studies revealed that transcription of the BDNF gene is regulated by SF-1, and that mutant SF-1 decreased BDNF promoter activation (similar to steroid enzyme promoters). However, clinical data from 16 subjects carrying SF-1 mutations showed normal birth weight and BMI. CONCLUSIONS: Glu7Stop and His408Profs*159 are novel SF-1 mutations identified in patients with 46,XY DSD and adrenal insufficiency (Glu7Stop). In vitro, SF-1 mutations affect not only steroidogenesis but also transcription of BDNF which is involved in energy balance. However, in contrast to mice, consequences on weight were not found in humans with SF-1 mutations. PMID- 25122492 TI - A review of the Fukushima nuclear reactor accident: radiation effects on the thyroid and strategies for prevention. AB - PURPOSE OF REVIEW: This is a summary of the nuclear accident at the Tokyo Electric Power Company Fukushima Daiichi Nuclear Power Stations (FDNPS) on 11 March 2011 to be used as a review of the radiation effects to the thyroid and strategies of prevention. RECENT FINDINGS: The amount of radioiodine released to the environment following the Fukushima accident was 120 Peta Becquerel, which is approximately one-tenth of that in the Chernobyl accident. Residents near the FDNPS were evacuated within a few days and foodstuffs were controlled within 1 or 2 weeks. Therefore, thyroid radiation doses were less than 100 mSv (intervention levels for stable iodine administration) in the majority of children, including less than 1 year olds, living in the evacuation areas. Because the incidence of childhood thyroid cancer increased in those residing near the site following the Chernobyl accident, thyroid screening of all children (0-18 years old) in the Fukushima Prefecture was started. To date, screening of more than 280 000 children has resulted in the diagnosis of thyroid cancer in 90 children (approximate incidence, 313 per million). Thus, although the dose of radiation was much lower, the incidence of thyroid cancer appears to be much higher than that following the Chernobyl accident. SUMMARY: A comparison of the thyroidal consequences following the Fukushima and Chernobyl nuclear reactor accidents is discussed. We also summarize the recent increased incidence in thyroid cancer in the Fukushima area following the accident in relation to increased thyroid ultrasound screening and the use of advanced ultrasound techniques. VIDEO ABSTRACT: http://links.lww.com/COE/A8. PMID- 25122491 TI - Psychiatric and cognitive manifestations of hypothyroidism. AB - PURPOSE OF REVIEW: Overt hypothyroidism has major effects on neuropsychiatric function, but patients with mild hypothyroidism may attribute unrelated neuropsychiatric symptoms to their thyroid condition. This review will summarize data on neuropsychiatric effects of hypothyroidism, and provide guidelines regarding the relationship between hypothyroidism and neuropsychiatric issues, and treatment indications. RECENT FINDINGS: Clinical investigations and functional imaging studies confirm that overt hypothyroidism is associated with affective and cognitive decrements, largely reversible with treatment. In contrast, subclinical hypothyroidism is not associated with major neuropsychiatric deficits, although studies utilizing sensitive measures show small deficits in memory and executive function. Neuropsychiatric complaints are more common when patients are aware of their thyroid disease, regardless of their thyroid function at the time of testing. SUMMARY: Neuropsychiatric dysfunction is common in overt hypothyroidism and will improve (perhaps not completely resolve) with therapy. Deficits related to thyroid dysfunction are usually mild in subclinical hypothyroidism, and realistic expectations need to be set regarding symptom reversibility with treatment. Patients with mild hypothyroidism and significant distress related to neuropsychiatric symptoms, most likely, have independent diagnoses that should be evaluated separately. PMID- 25122495 TI - MODMatcher: multi-omics data matcher for integrative genomic analysis. AB - Errors in sample annotation or labeling often occur in large-scale genetic or genomic studies and are difficult to avoid completely during data generation and management. For integrative genomic studies, it is critical to identify and correct these errors. Different types of genetic and genomic data are inter connected by cis-regulations. On that basis, we developed a computational approach, Multi-Omics Data Matcher (MODMatcher), to identify and correct sample labeling errors in multiple types of molecular data, which can be used in further integrative analysis. Our results indicate that inspection of sample annotation and labeling error is an indispensable data quality assurance step. Applied to a large lung genomic study, MODMatcher increased statistically significant genetic associations and genomic correlations by more than two-fold. In a simulation study, MODMatcher provided more robust results by using three types of omics data than two types of omics data. We further demonstrate that MODMatcher can be broadly applied to large genomic data sets containing multiple types of omics data, such as The Cancer Genome Atlas (TCGA) data sets. PMID- 25122493 TI - How sensitive (second-generation) thyroglobulin measurement is changing paradigms for monitoring patients with differentiated thyroid cancer, in the absence or presence of thyroglobulin autoantibodies. AB - PURPOSE OF REVIEW: To discuss new insights regarding how sensitive (second generation) thyroglobulin immunometric assays (TgIMAs), (functional sensitivities <=0.10 MUg/L) necessitate different approaches for postoperative thyroglobulin monitoring of patients with differentiated thyroid cancer (DTC), depending on the presence of thyroglobulin autoantibodies (TgAbs). RECENT FINDINGS: Reliable low range serum thyroglobulin measurement has both enhanced clinical utility and economic advantages, provided TgAb is absent (~75% DTC patients). Basal [nonthyroid-stimulating hormone (TSH) stimulated] TgIMA measurement obviates the need for recombinant human TSH stimulation because basal TgIMA below 0.20 MUg/L has comparable negative predictive value (>95%) to recombinant human TSH stimulated thyroglobulin values below the cutoff of 2 MUg/L. Now that radioiodine remnant ablation is no longer considered necessary to treat low-risk DTC, the trend and doubling time of low basal thyroglobulin values arising from postsurgical thyroid remnants have recognized prognostic significance. The major limitation of TgIMA testing is interference by TgAb (~25% DTC patients), causing TgIMA underestimation that can mask disease. When TgAb is present, the trend in TgAb concentrations (measured by the same method) can serve as the primary (surrogate) tumor-marker and be augmented by thyroglobulin measured by a TgAb resistant class of method (radioimmunoassay or liquid chromatography-tandem mass spectrometry). SUMMARY: The growing use of TgIMA measurement is changing paradigms for postoperative DTC monitoring. When TgAb is absent, it is optimal to monitor the basal TgIMA trend and doubling time (using the same method) in preference to recombinant human TSH-stimulated thyroglobulin testing. When TgAb is present, interference renders TgIMA testing unreliable and the trend in serum TgAb concentrations per se (same method) can serve as a (surrogate) tumor-marker. PMID- 25122496 TI - Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo. AB - A common strategy shared by all known gammaherpesviruses is their ability to establish a latent infection in lymphocytes--predominantly in B cells. In immunocompromised patients, such as transplant recipients or AIDS patients, gammaherpesvirus infections can lead to the development of lymphoproliferative disease and lymphoid malignancies. The human gamma-herpesviruses, EBV and KSHV, encode proteins that are capable of modulating the host immune signaling machinery, thereby subverting host immune responses. Murine gamma-herpesvirus 68 (MHV68) infection of laboratory strains of mice has proven to be useful small animal model that shares important pathogenic strategies with the human gamma herpesviruses. The MHV68 M2 protein is known to manipulate B cell signaling and, dependent on route and dose of virus inoculation, plays a role in both the establishment of latency and virus reactivation. M2 contains two tyrosines that are targets for phosphorylation, and have been shown to interact with the B cell signaling machinery. Here we describe in vitro and in vivo studies of M2 mutants which reveals that while both tyrosines Y120 and Y129 are required for M2 induction of IL-10 expression from primary murine B cells in vitro, only Y129 is critical for reactivation from latency and plasma cell differentiation in vivo. PMID- 25122497 TI - Controlling asthma by training of Capnometry-Assisted Hypoventilation (CATCH) vs slow breathing: a randomized controlled trial. AB - BACKGROUND: Hyperventilation has been associated with adverse effects on lung function, symptoms, and well-being in asthma. We examined whether raising end tidal CO2 levels (ie, Pco2) compared with slow breathing is associated with improvements in asthma control, including peak flow variability. METHODS: One hundred twenty patients with asthma were randomly assigned to capnometry-assisted respiratory training (CART) for raising Pco2 or slow breathing and awareness training (SLOW) for slowing respiratory rate. Patients received five weekly sessions and completed bid homework exercises over 4 weeks. Blinded assessments at baseline, posttreatment, 1- and 6-month follow-up of asthma control, Pco2, and diurnal peak flow variability were primary outcome measures. Additionally, we measured pulmonary function (spirometry, forced oscillation, exhaled nitric oxide, and methacholine challenge), symptoms, quality of life, and bronchodilator use. Because the control group received active treatment, we expected improvements in asthma control in both groups but more pronounced benefits from CART. RESULTS: Improvements were seen in 17 of 21 clinical indexes (81.0%) in both interventions, including the primary outcome variables asthma control (d = 0.81), peak flow variability (d = 0.54), quality of life, bronchodilator use, lung function, and airway hyperreactivity. Most improvements were sustained across the 6-month follow-up. Compared with slow breathing, CART showed greater increases in Pco2 (d = 1.45 vs 0.64 for CART vs SLOW, respectively) and greater reductions in respiratory impedance during treatment, less distress during methacholine challenge, and greater reduction in asthma symptoms at follow-up (P < .05). CONCLUSIONS: Brief interventions aimed at raising Pco2 or slowing respiratory rate provide significant, sustained, and clinically meaningful improvements in asthma control. Raising Pco2 was associated with greater benefits in aspects of lung function and long-term symptoms. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00975273; URL: www.clinicaltrials.gov. PMID- 25122498 TI - Bursts and heavy tails in temporal and sequential dynamics of foraging decisions. AB - A fundamental understanding of behavior requires predicting when and what an individual will choose. However, the actual temporal and sequential dynamics of successive choices made among multiple alternatives remain unclear. In the current study, we tested the hypothesis that there is a general bursting property in both the timing and sequential patterns of foraging decisions. We conducted a foraging experiment in which rats chose among four different foods over a continuous two-week time period. Regarding when choices were made, we found bursts of rapidly occurring actions, separated by time-varying inactive periods, partially based on a circadian rhythm. Regarding what was chosen, we found sequential dynamics in affective choices characterized by two key features: (a) a highly biased choice distribution; and (b) preferential attachment, in which the animals were more likely to choose what they had previously chosen. To capture the temporal dynamics, we propose a dual-state model consisting of active and inactive states. We also introduce a satiation-attainment process for bursty activity, and a non-homogeneous Poisson process for longer inactivity between bursts. For the sequential dynamics, we propose a dual-control model consisting of goal-directed and habit systems, based on outcome valuation and choice history, respectively. This study provides insights into how the bursty nature of behavior emerges from the interaction of different underlying systems, leading to heavy tails in the distribution of behavior over time and choices. PMID- 25122500 TI - Plasminogen activator inhibitor-1 in aging. AB - Plasminogen activator inhibitor-1 (PAI-1), a principal inhibitor of fibrinolysis, is induced in thrombotic, fibrotic, and cardiovascular diseases, which in turn primarily afflict the older population. This induction of PAI-1 may play an important role in the pathology of these diseases as PAI-1 can regulate the dissolution of fibrin and also inhibit the degradation of the extracellular matrix by reducing plasmin generation. PAI-1 expression is elevated in aged individuals and is significantly upregulated in a variety of pathologies associated with the process of aging, including myocardial and cerebral infarction, vascular (athero) sclerosis, cardiac and lung fibrosis, metabolic syndromes (e.g., hypertension, hyperlipidemia, and insulin resistance), cancer, and inflammatory/stress responses. Thus, PAI-1 may play a critical role in the development of aging-associated pathological changes. In addition, PAI-1 is recognized as a marker of senescence and a key member of a group of proteins collectively known as the senescence-messaging secretome. In this review, we highlight the role of PAI-1 in the pathophysiology of aging and aging-associated disorders. PMID- 25122499 TI - Thermostability of in vitro evolved Bacillus subtilis lipase A: a network and dynamics perspective. AB - Proteins in thermophilic organisms remain stable and function optimally at high temperatures. Owing to their important applicability in many industrial processes, such thermostable proteins have been studied extensively, and several structural factors attributed to their enhanced stability. How these factors render the emergent property of thermostability to proteins, even in situations where no significant changes occur in their three-dimensional structures in comparison to their mesophilic counter-parts, has remained an intriguing question. In this study we treat Lipase A from Bacillus subtilis and its six thermostable mutants in a unified manner and address the problem with a combined complex network-based analysis and molecular dynamic studies to find commonality in their properties. The Protein Contact Networks (PCN) of the wild-type and six mutant Lipase A structures developed at a mesoscopic scale were analyzed at global network and local node (residue) level using network parameters and community structure analysis. The comparative PCN analysis of all proteins pointed towards important role of specific residues in the enhanced thermostability. Network analysis results were corroborated with finer-scale molecular dynamics simulations at both room and high temperatures. Our results show that this combined approach at two scales can uncover small but important changes in the local conformations that add up to stabilize the protein structure in thermostable mutants, even when overall conformation differences among them are negligible. Our analysis not only supports the experimentally determined stabilizing factors, but also unveils the important role of contacts, distributed throughout the protein, that lead to thermostability. We propose that this combined mesoscopic-network and fine-grained molecular dynamics approach is a convenient and useful scheme not only to study allosteric changes leading to protein stability in the face of negligible over-all conformational changes due to mutations, but also in other molecular networks where change in function does not accompany significant change in the network structure. PMID- 25122502 TI - Quick and label-free detection for Coumaphos by using surface plasmon resonance biochip. AB - Coumaphos is a common organophosphorus pesticide used in agricultural products. It is harmful to human health and has a strictly stipulated maximum residue limit (MRL) on fruits and vegetables. Currently existing methods for detection are complex in execution, require expensive tools and are time consuming and labor intensive. The surface plasmon resonance method has been widely used in biomedicine and many other fields. This study discusses a detection method based on surface plasmon resonance in organophosphorus pesticide residues. As an alternative solution, this study proposes a method to detect Coumaphos. The method, which is based on surface plasmon resonance (SPR) and immune reaction, belongs to the suppression method. A group of samples of Coumaphos was detected by this method. The concentrations of Coumaphos in the samples were 0 ug/L, 50 ug/L, 100 ug/L, 300 ug/L, 500 ug/L, 1000 ug/L, 3000 ug/L and 5000 ug/L, respectively. Through detecting a group of samples, the process of kinetic reactions was analyzed and the corresponding standard curve was obtained. The sensibility is less than 25 ug/L, conforming to the standard of the MRL of Coumaphos stipulated by China. This method is label-free, using an unpurified single antibody only and can continuously test at least 80 groups of samples continuously. It has high sensitivity and specificity. The required equipments are simple, environmental friendly and easy to control. So this method is promised for a large number of samples quick detection on spot and for application prospects. PMID- 25122501 TI - Dissemination of Orientia tsutsugamushi and inflammatory responses in a murine model of scrub typhus. AB - Central aspects in the pathogenesis of scrub typhus, an infection caused by Orientia (O.) tsutsugamushi, have remained obscure. Its organ and cellular tropism are poorly understood. The purpose of this study was to analyze the kinetics of bacterial dissemination and associated inflammatory responses in infected tissues in an experimental scrub typhus mouse model, following infection with the human pathogenic strain Karp. We provide a thorough analysis of O. tsutsugamushi infection in inbred Balb/c mice using footpad inoculation, which is close to the natural way of infection. By a novel, highly sensitive qPCR targeting the multi copy traD genes, we quantitatively monitored the spread of O. tsutsugamushi Karp from the skin inoculation site via the regional lymph node to the internal target organs. The highest bacterial loads were measured in the lung. Using confocal imaging, we also detected O. tsutsugamushi at the single cell level in the lung and found a predominant macrophage rather than endothelial localization. Immunohistochemical analysis of infiltrates in lung and brain revealed differently composed lesions with specific localizations: iNOS expressing macrophages were frequent in infiltrative parenchymal noduli, but uncommon in perivascular lesions within these organs. Quantitative analysis of the macrophage response by immunohistochemistry in liver, heart, lung and brain demonstrated an early onset of macrophage activation in the liver. Serum levels of interferon (IFN)-gamma were increased during the acute infection, and we showed that IFN-gamma contributed to iNOS-dependent bacterial growth control. Our data show that upon inoculation to the skin, O. tsutsugamushi spreads systemically to a large number of organs and gives rise to organ-specific inflammation patterns. The findings suggest an essential role for the lung in the pathogenesis of scrub typhus. The model will allow detailed studies on host pathogen interaction and provide further insight into the pathogenesis of O. tsutsugamushi infection. PMID- 25122503 TI - Nicotine intake from electronic cigarettes on initial use and after 4 weeks of regular use. AB - INTRODUCTION: Electronic cigarettes (EC) have the potential to generate a substantial public health benefit if there is a switch from smoking to EC use on a population scale. The nicotine delivery from EC is likely to play a major role in their attractiveness to smokers. We assessed nicotine delivery from a first generation EC and the effect of experience with its use on nicotine intake. METHODS: Six smokers provided pharmacokinetic (PK) data after their first use of EC and again following 4 weeks of use. RESULTS: The peak nicotine levels were achieved within 5 min of starting the EC use, which suggests that EC may provide nicotine via pulmonary absorption. There were large individual differences in nicotine intake. Compared with the PK profile when using EC for the first time, 4 weeks of practice generated a 24% increase in the peak plasma concentrations (from 4.6 to 5.7 ng/ml; nonsignificant) and a 79% increase in overall nicotine intake (AUC(0 -> inf) increased from 115 to 206 ng*min/ml; p < .05). CONCLUSIONS: First-generation EC provide faster nicotine absorption than nicotine replacement products, but to compete successfully with conventional cigarettes, EC may need to provide higher doses of nicotine. Nicotine intake from EC can increase with practice, but further studies are needed to confirm this effect. PMID- 25122504 TI - A maladaptive role for EP4 receptors in mouse mesangial cells. AB - Roles of the prostaglandin E2 E-prostanoid 4 receptor (EP4) on extracellular matrix (ECM) accumulation induced by TGF-beta1 in mouse glomerular mesangial cells (GMCs) remain unknown. Previously, we have identified that TGF-beta1 stimulates the expression of FN and Col I in mouse GMCs. Here we asked whether stimulation of EP4 receptors would exacerbate renal fibrosis associated with enhanced glomerular ECM accumulation. We generated EP4(Flox/Flox) and EP4(+/-) mice, cultured primary WT, EP4(Flox/Flox) and EP4(+/-) GMCs, AD-EP4 transfected WT GMCs (EP4 overexpression) and AD-Cre transfected EP4(Flox/Flox) GMCs (EP4 deleted). We found that TGF-beta1-induced cAMP and PGE2 synthesis decreased in EP4 deleted GMCs and increased in EP4 overexpressed GMCs. Elevated EP4 expression in GMCs augmented the coupling of TGF-beta1 to FN, Col I expression and COX2/PGE2 signaling, while TGF-beta1 induced FN, Col I expression and COX2/PGE2 signaling were down-regulated in EP4 deficiency GMCs. 8 weeks after 5/6 nephrectomy (Nx), WT and EP4(+/-) mice exhibited markedly increased accumulation of ECM compared with sham-operated controls. Albuminuria, blood urea nitrogen and creatinine (BUN and Cr) concentrations were significantly increased in WT mice as compared to those of EP4(+/-) mice. Urine osmotic pressure was dramatically decreased after 5/6 Nx surgery in WT mice as compared to EP4(+/-) mice. The pathological changes in kidney of EP4(+/-) mice was markedly alleviated compared with WT mice. Immunohistochemical analysis showed significant reductions of Col I and FN in the kidney of EP4(+/-) mice compared with WT mice. Collectively, this investigation established EP4 as a potent mediator of the pro-TGF-beta1 activities elicited by COX2/PGE2 in mice GMCs. Our findings suggested that prostaglandin E2, acting via EP4 receptors contributed to accumulation of ECM in GMCs and promoted renal fibrosis. PMID- 25122506 TI - Minimally invasive intervention for infected necrosis in acute pancreatitis. AB - Infected necrosis is the main indication for invasive intervention in acute necrotizing pancreatitis. The 2013 IAP/APA guidelines state that percutaneous catheter drainage should be the first step in the treatment of infected necrosis. In 50-65% of patients, additional necrosectomy is required after catheter drainage, which was traditionally done by open necrosectomy. Driven by the perceived lower complication rate, there is an increasing trend toward minimally invasive percutaneous and endoscopic transluminal necrosectomy. The authors present an overview of current minimally invasive treatment options for necrotizing pancreatitis and review recent developments in clinical studies. PMID- 25122505 TI - Antiplatelet effect of catechol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A2 production. AB - Catechol (benzenediol) is present in plant-derived products, such as vegetables, fruits, coffee, tea, wine, areca nut and cigarette smoke. Because platelet dysfunction is a risk factor of cardiovascular diseases, including stroke, atherosclerosis and myocardial infarction, the purpose of this study was to evaluate the anti-platelet and anti-inflammatory effect of catechol and its mechanisms. The effects of catechol on cyclooxygenase (COX) activity, arachidonic acid (AA)-induced aggregation, thromboxane B2 (TXB2) production, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production and extracellular signal-regulated kinase (ERK)/p38 phosphorylation were determined in rabbit platelets. In addition, its effect on IL-1beta-induced prostaglandin E2 (PGE2) production by fibroblasts was determined. The ex vivo effect of catechol on platelet aggregation was also measured. Catechol (5-25 uM) suppressed AA induced platelet aggregation and inhibited TXB2 production at concentrations of 0.5-5 uM; however, it showed little cytotoxicity and did not alter U46619-induced platelet aggregation. Catechol (10-50 uM) suppressed COX-1 activity by 29-44% and COX-2 activity by 29-50%. It also inhibited IL-1beta-induced PGE2 production, but not COX-2 expression of fibroblasts. Moreover, catechol (1-10 uM) attenuated AA induced ROS production in platelets and phorbol myristate acetate (PMA)-induced ROS production in human polymorphonuclear leukocytes. Exposure of platelets to catechol decreased AA-induced ERK and p38 phosphorylation. Finally, intravenous administration of catechol (2.5-5 umole/mouse) attenuated ex vivo AA-induced platelet aggregation. These results suggest that catechol exhibited anti-platelet and anti-inflammatory effects, which were mediated by inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation. The anti-platelet effect of catechol was confirmed by ex vivo analysis. Exposure to catechol may affect platelet function and thus cardiovascular health. PMID- 25122507 TI - Domain organization, catalysis and regulation of eukaryotic cystathionine beta synthases. AB - Cystathionine beta-synthase (CBS) is a key regulator of sulfur amino acid metabolism diverting homocysteine, a toxic intermediate of the methionine cycle, via the transsulfuration pathway to the biosynthesis of cysteine. Although the pathway itself is well conserved among eukaryotes, properties of eukaryotic CBS enzymes vary greatly. Here we present a side-by-side biochemical and biophysical comparison of human (hCBS), fruit fly (dCBS) and yeast (yCBS) enzymes. Preparation and characterization of the full-length and truncated enzymes, lacking the regulatory domains, suggested that eukaryotic CBS exists in one of at least two significantly different conformations impacting the enzyme's catalytic activity, oligomeric status and regulation. Truncation of hCBS and yCBS, but not dCBS, resulted in enzyme activation and formation of dimers compared to native tetramers. The dCBS and yCBS are not regulated by the allosteric activator of hCBS, S-adenosylmethionine (AdoMet); however, they have significantly higher specific activities in the canonical as well as alternative reactions compared to hCBS. Unlike yCBS, the heme-containing dCBS and hCBS showed increased thermal stability and retention of the enzyme's catalytic activity. The mass-spectrometry analysis and isothermal titration calorimetry showed clear presence and binding of AdoMet to yCBS and hCBS, but not dCBS. However, the role of AdoMet binding to yCBS remains unclear, unlike its role in hCBS. This study provides valuable information for understanding the complexity of the domain organization, catalytic specificity and regulation among eukaryotic CBS enzymes. PMID- 25122510 TI - The palliative performance scale applied in high-care residential hospice: a retrospective study. AB - BACKGROUND: The Palliative Performance Scale (PPS) is a tool that is widely used to predict end of life. In Ontario, Canada, the PPS is used to mark the terminal phase of life and eligibility for terminal care. OBJECTIVE: The aim of this retrospective study was to confirm that a PPS level of 40% can be used as a marker for the terminal phase of life. METHOD: PPS levels from 78 patients were calculated based on the intake reports made at admission to an inpatient hospice. RESULTS: Although 77 patients passed away within a period of 3 months, PPS levels at admission varied from 10% to 70%. Fifty-six percent of all patients had a PPS level of 40% or less. Regarding survival, three significant PPS profiles, consisting of two or more PPS levels could be distinguished. PMID- 25122508 TI - Saccadic eye movements in depressed elderly patients. AB - The primary aim of this study was to characterize oculomotor performances in elderly depressed patients. The second aim was to investigate whether cognitive inhibition measured by the antisaccade task was associated with a psychomotor retardation or rather with a more specific cognitive-motor inhibition deficit. Twenty patients with a major depressive disorder and forty-seven healthy subjects performed two eye movement tasks. Saccadic reaction time and error rates were analyzed in the prosaccade task to obtain basic parameters of eye movements. Saccade latency, error rates and correction rates were evaluated in the antisaccade task to investigate inhibition capacities. Performances were impaired in patients, who exhibited a higher reaction time and error rates compared to controls. The higher time cost of inhibition suggested that the reaction time was not related to global psychomotor retardation alone. The higher time cost of inhibition could be explained by a specific alteration of inhibition processes evaluated by the antisaccade task. These changes were associated with the severity of depression. These findings provide a new perspective on cognitive inhibition in elderly depressed patients and could have important clinical implications for our understanding of critical behaviors involving deficits in inhibitory processes in the elderly. PMID- 25122511 TI - Poisson indicator and Fano factor for probing dynamic disorder in single-molecule enzyme inhibition kinetics. AB - We consider a generic stochastic model to describe the kinetics of single molecule enzyme inhibition reactions in which the turnover events correspond to conversion of substrate into a product by a single enzyme molecule in the presence of an inhibitor. We observe that slow fluctuations between the active and inhibited state of the enzyme or the enzyme substrate complex can induce dynamic disorder, which is manifested in the measurement of the Poisson indicator and the Fano factor as functions of substrate concentrations for different inhibition reactions. For a single enzyme molecule inhibited by the product, we derive a single-molecule Michaelis-Menten equation for the reaction rate, which shows a dependence on the substrate concentration similar to the ensemble enzymatic catalysis rate as obtained from bulk experimental results. The measurement of Fano factor is shown to be able to discriminate reactions following different inhibition mechanisms and also extract kinetic rates. PMID- 25122509 TI - Effects of baseline problematic alcohol and drug use on internet-based cognitive behavioral therapy outcomes for depression, panic disorder and social anxiety disorder. AB - PURPOSE: Patients' problematic substance use prevalence and effects were explored in relation to internet-based cognitive behavioral therapy (ICBT) outcomes for depression, panic disorder and social anxiety disorder. METHODS: At baseline and treatment conclusion, 1601 ICBT patients were assessed with self-rated measures for alcohol and drug use (AUDIT/DUDIT), depressive symptoms (MADRS-S), panic disorder symptoms (PDSS-SR) and social anxiety symptoms (LSAS-SR). RESULTS: Problematic substance use (AUDIT >= 8 for men, >= 6 for women; DUDIT >= 1) occurred among 32.4% of the patients; 24.1% only alcohol, 4.6% only drugs, and 3.7% combined alcohol and drug use. Hazardous alcohol use and probable alcohol dependence negatively affected panic disorder outcomes, and hazardous drug use led to worse social anxiety outcomes. Depression outcomes were not affected by substance use. Treatment adherence was negatively affected by problematic drug use among men and 25-34 year olds; combined substance use negatively affected adherence for women and 35-64 year olds. CONCLUSION: Problematic substance use does not preclude ICBT treatment but can worsen outcomes, particularly problematic alcohol use for panic disorder patients and hazardous drug use for social anxiety patients. ICBT clinicians should exercise particular caution when treating men and younger patients with problematic drug use, and women or older patients with combined substance use. PMID- 25122512 TI - Ultrasound current source density imaging of the cardiac activation wave using a clinical cardiac catheter. AB - Ultrasound current source density imaging (UCSDI), based on the acoustoelectric (AE) effect, is a noninvasive method for mapping electrical current in 4-D (space + time). This technique potentially overcomes limitations with conventional electrical mapping procedures typically used during treatment of sustained arrhythmias. However, the weak AE signal associated with the electrocardiogram is a major challenge for advancing this technology. In this study, we examined the effects of the electrode configuration and ultrasound frequency on the magnitude of the AE signal and quality of UCSDI using a rabbit Langendorff heart preparation. The AE signal was much stronger at 0.5 MHz (2.99 MUV/MPa) than 1.0 MHz (0.42 MUV/MPa). Also, a clinical lasso catheter placed on the epicardium exhibited excellent sensitivity without penetrating the tissue. We also present, for the first time, 3-D cardiac activation maps of the live rabbit heart using only one pair of recording electrodes. Activation maps were used to calculate the cardiac conduction velocity for atrial (1.31 m/s) and apical (0.67 m/s) pacing. This study demonstrated that UCSDI is potentially capable of real-time 3-D cardiac activation wave mapping, which would greatly facilitate ablation procedures for treatment of arrhythmias. PMID- 25122514 TI - We are both doctors: an Israeli doctor writes to a Palestinian colleague. PMID- 25122513 TI - Cationic charged helical glycopolypeptide using ring opening polymerization of 6 deoxy-6-azido-glyco-N-carboxyanhydride. AB - Glycopolypeptides with a defined secondary structure are of significance in understanding biological phenomena. Synthetic glycopolypeptides, or polypeptides featuring pendant carbohydrate moieties, have been of particular interest in the field of tissue engineering and drug delivery. In this work, we have synthesized charged water-soluble glycopolypeptides that adopt a helical conformation in water. This was carried out by the synthesis of a glyco-N-carboxyanhydride (glyco NCA) containing an azide group at the sixth position of the carbohydrate ring. Subsequently, the NCA was polymerized to obtain azide-containing glycopolypeptides having good control over molecular weight and polydispersity index (PDI) in high yields. We were also able to control the incorporation of the azide group by synthesizing random co-glycopolypeptide containing 6-deoxy-6-azido and regular 6-OAc functionalized glucose. This azide functionality allows for the easy attachment of a bioactive group, which could potentially enhance the biological activity of the glycopolypeptide. We were able to obtain water-soluble charged glycopolypeptides by both reducing the azide groups into amines and using CuAAC with propargylamine. These charged glycopolypeptides were shown to have a helical conformation in water. Preliminary studies showed that these charged glycopolypeptides showed good biocompatibility and were efficiently taken up by HepG2 cells. PMID- 25122515 TI - Steered quantum dynamics for energy minimization. AB - We introduce a quantum optimal control algorithm for energy minimization that combines the diffeomorphic modulation under observable response preserving homotopy (D-MORPH) gradient and the Broyden Fletcher Goldfarb Shanno (BFGS) iterative scheme for nonlinear optimization. An extended set of controls defining the time-dependent mass, dipole moment, and external perturbational field are optimized to find an effective Hamiltonian that steers the dynamics of the system into the global minimum without getting trapped into local minima. The algorithm is illustrated as applied to energy minimization on rugged surfaces and golf potentials comparable to those previously explored for testing quantum annealing methodologies. PMID- 25122517 TI - Characteristics of persons with corrective lenses, United States -1971. AB - This report from the Health Interview Survey presents data on the use of corrective lenses for persons 3 years of age and over. Estimates are derived from a survey during 1971 of the civilian, noninstitutionalized population of the United States. Corrective lenses include eyeglasses and contact lenses. The term "corrective Ienses" is limited to visual aids worn to correct or improve vision and therefore excludes sunglasses worn only to filter light, safety glasses worn only for protection of the eyes, hand magnifying glasses, and other such devices. However, if the safety glasses are worn also for correction or improvement of vision, they are considered corrective lenses, as are prescription glasses. This report analyzes use of corrective Ienses by various demographic characteristics. An earlier report from the Health Interview Survey presented data on corrective lenses based on the July 1965-June 1966 survey. It contained information on age at which persons first obtained corrective lenses, type of prescription, usage, and the source of the optical examination if the individual was examined during the 2-year period prior to interview ("Characteristics of Persons with Corrective Lenses: United States, July 1965-June 1966," Vital and Health Statistics, Series 10, Number 53). A later section of the present report compares demographic differences in the proportion of the population with corrective lenses for the two time periods. PMID- 25122516 TI - Infrageneric phylogeny and temporal divergence of Sorghum (Andropogoneae, Poaceae) based on low-copy nuclear and plastid sequences. AB - The infrageneric phylogeny and temporal divergence of Sorghum were explored in the present study. Sequence data of two low-copy nuclear (LCN) genes, phosphoenolpyruvate carboxylase 4 (Pepc4) and granule-bound starch synthase I (GBSSI), from 79 accessions of Sorghum plus Cleistachne sorghoides together with those from outgroups were used for maximum likelihood (ML) and Bayesian inference (BI) analyses. Bayesian dating based on three plastid DNA markers (ndhA intron, rpl32-trnL, and rps16 intron) was used to estimate the ages of major diversification events in Sorghum. The monophyly of Sorghum plus Cleistachne sorghoides (with the latter nested within Sorghum) was strongly supported by the Pepc4 data using BI analysis, and the monophyly of Sorghum was strongly supported by GBSSI data using both ML and BI analyses. Sorghum was divided into three clades in the Pepc4, GBSSI, and plastid phylograms: the subg. Sorghum lineage; the subg. Parasorghum and Stiposorghum lineage; and the subg. Chaetosorghum and Heterosorghum lineage. Two LCN homoeologous loci of Cleistachne sorghoides were first discovered in the same accession. Sorghum arundinaceum, S. bicolor, S. x drummondii, S. propinquum, and S. virgatum were closely related to S. x almum in the Pepc4, GBSSI, and plastid phylograms, suggesting that they may be potential genome donors to S. almum. Multiple LCN and plastid allelic variants have been identified in S. halepense of subg. Sorghum. The crown ages of Sorghum plus Cleistachne sorghoides and subg. Sorghum are estimated to be 12.7 million years ago (Mya) and 8.6 Mya, respectively. Molecular results support the recognition of three distinct subgenera in Sorghum: subg. Chaetosorghum with two sections, each with a single species, subg. Parasorghum with 17 species, and subg. Sorghum with nine species and we also provide a new nomenclatural combination, Sorghum sorghoides. PMID- 25122518 TI - Synthesis of neplanocin A and its 3'-epimer via an intramolecular Baylis-Hillman reaction. AB - The key cyclopentenyl intermediate 11b was synthesized in 4 steps from d-ribose in 41% overall yield via an efficient intramolecular Baylis-Hillman reaction. This novel key intermediate can be modified easily and transformed to neplanocin A (1a) and its 3'-epimer (1b). PMID- 25122519 TI - Breast-cancer patients' participation behavior and coping during presurgical consultations: a pilot study. AB - In the context of breast-cancer care, there is extremely little research on the association between observed (i.e., taped and coded) communication behaviors and patients' health outcomes, especially those other than satisfaction. In the context of presurgical consultations between female breast cancer patients and a surgeon, the aim of this exploratory study was to test the association between communication-based participation behaviors and pre-post consultation changes in aspects of patients' mental adjustment to cancer (i.e., coping). Participants included 51 women newly diagnosed with breast cancer and a surgical oncologist from a National Cancer Institute (NCI)-designated cancer center in the northeastern United States. Outcomes were changes in patients' fighting spirit, helplessness/hopelessness, anxious preoccupation, cognitive avoidance, and fatalism (measured immediately before and after consultations via survey), and the main predictors were three communication-based participation behaviors coded from videotapes of consultations: patient question asking, patient assertion of treatment preferences, and surgeon solicitation of patient question/concern/opinion. Patients who more frequently asserted their treatment preferences experienced increases in their fighting spirit (p = .01) and decreases in their anxious preoccupation (p = .02). When companions (e.g., sister, spouse) asked more questions, patients experienced decreases in their anxious preoccupation (p = .05). These findings suggest that, in the present context, there may be specific, trainable communication behaviors, such as patients asserting their treatment preferences and companions asking questions, that may improve patients' psychosocial health outcomes. PMID- 25122520 TI - A mitochondria-targetable fluorescent probe for dual-channel NO imaging assisted by intracellular cysteine and glutathione. AB - A mitochondria-specific fluorescent probe for NO (1) was synthesized by the direct conjugation of a pyronin dye with one of the amino groups of o phenylenediamino (OPD). The probe could selectively detect NO over dehydroascorbic acid (DHA), ascorbic acid (AA), and methylglyoxal (MGO) as well as the reactive oxygen/nitrogen species (ROS/RNS) with the significant off-on response due to the production of a red-emission triazole 2. In the presence of cysteine/glutathione (Cys/GSH), 2 could be further transformed into a green emission aminopyronin 4 and a red-emission thiopyronin 5, respectively. Assisted by intracellular Cys and GSH, the probe demonstrated its potential to monitor mitochondrial NO in a dual-channel mode. PMID- 25122521 TI - "The Castle of Remembrance": New insights from a cognitive training programme for autobiographical memory in Alzheimer's disease. AB - Autobiographical memory deficits are prominent from the early stages of Alzheimer's disease (AD) and result in a loss of personal identity. Nevertheless, standardised methods of autobiographical memory stimulation for the neuropsychological rehabilitation of patients with AD remain underdeveloped. Our aim was to evaluate the impact of a new cognitive training programme for autobiographical memory (REMau) on both the episodic and semantic components of autobiographical memory performance across lifetime periods, as well as on mood. Pre/post evaluations were conducted on two groups of patients with early to moderate AD, assigned to one of two different training activities: either the REMau or a cognitive training programme focused on collective semantic memory. Statistical comparisons showed significant improvement of episodic and semantic autobiographical memory performance in the REMau group, which was more pronounced for the semantic component, as well as improved mood. By contrast, deleterious pre/post differences were observed in the other group. Most interestingly, this study showed that the REMau programme boosted autobiographical memory from the reminiscence bump period, which is considered crucial for the construction and maintenance of personal identity. We discuss the theoretical and practical implications of these results for the reduction of autobiographical memory deficits in AD. PMID- 25122522 TI - Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography. AB - We have recently established a procedure for serial femtosecond crystallography (SFX) in lipidic cubic phase (LCP) for protein structure determination at X-ray free-electron lasers (XFELs). LCP-SFX uses the gel-like LCP as a matrix for growth and delivery of membrane protein microcrystals for crystallographic data collection. LCP is a liquid-crystalline mesophase composed of lipids and water. It provides a membrane-mimicking environment that stabilizes membrane proteins and supports their crystallization. Here we describe detailed procedures for the preparation and characterization of microcrystals for LCP-SFX applications. The advantages of LCP-SFX over traditional crystallographic methods include the capability of collecting room-temperature high-resolution data with minimal effects of radiation damage from sub-10-MUm crystals of membrane and soluble proteins that are difficult to crystallize, while eliminating the need for crystal harvesting and cryo-cooling. Compared with SFX methods for microcrystals in solution using liquid injectors, LCP-SFX reduces protein consumption by 2-3 orders of magnitude for data collection at currently available XFELs. The whole procedure typically takes 3-5 d, including the time required for the crystals to grow. PMID- 25122523 TI - Addition of exogenous alpha-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous alpha-synuclein to Lewy body and Lewy neurite-like aggregates. AB - This protocol describes a primary neuronal model of formation of alpha-synuclein (alpha-syn) aggregates that recapitulate features of the Lewy bodies and Lewy neurites found in Parkinson's disease brains and other synucleinopathies. This model allows investigation of aggregate formation, their impact on neuron function, and development of therapeutics. Addition of preformed fibrils (PFFs) synthesized from recombinant alpha-syn to neurons seeds the recruitment of endogenous alpha-syn into aggregates characterized by detergent insolubility and hyperphosphorylation. Aggregate formation follows a lag phase of 2-3 d, followed by formation in axons by days 4-7, spread to somatodendritic compartments by days 7-10 and neuron death ~14 d after PFF addition. Here we provide methods and highlight the crucial steps for PFF formation, PFF addition to cultured hippocampal neurons and confirmation of aggregate formation. Neurons derived from various brain regions from nontransgenic and genetically engineered mice and rats can be used, allowing interrogation of the effect of specific genes on aggregate formation. PMID- 25122524 TI - Similarity-based modeling in large-scale prediction of drug-drug interactions. AB - Drug-drug interactions (DDIs) are a major cause of adverse drug effects and a public health concern, as they increase hospital care expenses and reduce patients' quality of life. DDI detection is, therefore, an important objective in patient safety, one whose pursuit affects drug development and pharmacovigilance. In this article, we describe a protocol applicable on a large scale to predict novel DDIs based on similarity of drug interaction candidates to drugs involved in established DDIs. The method integrates a reference standard database of known DDIs with drug similarity information extracted from different sources, such as 2D and 3D molecular structure, interaction profile, target and side-effect similarities. The method is interpretable in that it generates drug interaction candidates that are traceable to pharmacological or clinical effects. We describe a protocol with applications in patient safety and preclinical toxicity screening. The time frame to implement this protocol is 5-7 h, with additional time potentially necessary, depending on the complexity of the reference standard DDI database and the similarity measures implemented. PMID- 25122526 TI - Metal-free sp(3) C-H functionalization: a novel approach for the syntheses of selenide ethers and thioesters from methyl arenes. AB - A DTBP-promoted metal-free and solvent-free formation of C-Se and C-S bonds through sp(3) C-H functionalization of methyl arenes with diselenides and disulfides is described. PMID- 25122527 TI - It's all in the communication. PMID- 25122525 TI - Tracheal tissue engineering in rats. AB - Tissue-engineered tracheal transplants have been successfully performed clinically. However, before becoming a routine clinical procedure, further preclinical studies are necessary to determine the underlying mechanisms of in situ tissue regeneration. Here we describe a protocol using a tissue engineering strategy and orthotopic transplantation of either natural decellularized donor tracheae or artificial electrospun nanofiber scaffolds into a rat model. The protocol includes details regarding how to assess the scaffolds' biomechanical properties and cell viability before implantation. It is a reliable and reproducible model that can be used to investigate the crucial aspects and pathways of in situ tracheal tissue restoration and regeneration. The model can be established in <6 months, and it may also provide a means to investigate cell surface interactions, cell differentiation and stem cell fate. PMID- 25122528 TI - Current estimates, from the health interview survey, United States-1972. AB - National estimates of the basic health variables collected in the 1972 Health Interview Survey of the civilian noninstitutionalized population are presented in this report. While the detailed tables in this report contain data by age and sex categories, later reports will present more detailed analysis of similar data by additional selected demographic variables. The text tables present data for 1970 and 1971 as well as for 1972; however, the discussion is limited largely to changes occurring between 1971 and 1972, since the previous report (Current Estimates, Series 10, No. 79) compares the 1970 and 1971 data. PMID- 25122529 TI - Use of Systematic Methods to Improve Disease Identification in Administrative Data: The Case of Severe Sepsis. AB - BACKGROUND: Selection of International Classification of Diseases (ICD)-based coded information for complex conditions such as severe sepsis is a subjective process and the results are sensitive to the codes selected. We use an innovative data exploration method to guide ICD-based case selection for severe sepsis. METHODS: Using the Nationwide Inpatient Sample, we applied Latent Class Analysis (LCA) to determine if medical coders follow any uniform and sensible coding for observations with severe sepsis. We examined whether ICD-9 codes specific to sepsis (038.xx for septicemia, a subset of 995.9 codes representing Systemic Inflammatory Response syndrome, and 785.52 for septic shock) could all be members of the same latent class. RESULTS: Hospitalizations coded with sepsis-specific codes could be assigned to a latent class of their own. This class constituted 22.8% of all potential sepsis observations. The probability of an observation with any sepsis-specific codes being assigned to the residual class was near 0. The chance of an observation in the residual class having a sepsis-specific code as the principal diagnosis was close to 0. Validity of sepsis class assignment is supported by empirical results, which indicated that in-hospital deaths in the sepsis-specific class were around 4 times as likely as that in the residual class. CONCLUSIONS: The conventional methods of defining severe sepsis cases in observational data substantially misclassify sepsis cases. We suggest a methodology that helps reliable selection of ICD codes for conditions that require complex coding. PMID- 25122530 TI - Persistent medication affordability problems among disabled Medicare beneficiaries after Part D, 2006-2011. AB - BACKGROUND: Disabled Americans who qualify for Medicare coverage typically have multiple chronic conditions, are highly dependent on effective drug therapy, and have limited financial resources, putting them at risk for cost-related medication nonadherence (CRN). Since 2006, the Part D benefit has helped Medicare beneficiaries afford medications. OBJECTIVE: To investigate recent national trends in medication affordability among this vulnerable population, stratified by morbidity burden. DESIGN AND SUBJECTS: We estimated annual rates of medication affordability among nonelderly disabled participants in a nationally representative survey (2006-2011, n=14,091 person-years) using multivariate logistic regression analyses. MEASURE: Survey-reported CRN and spending less on other basic needs to afford medicines. RESULTS: In the 6 years following Part D implementation, the proportion of disabled Medicare beneficiaries reporting CRN ranged from 31.6% to 35.6%, while the reported prevalence of spending less on other basic needs to afford medicines ranged from 17.7% to 21.8%. Across study years, those with multiple chronic conditions had consistently worse affordability problems. In 2011, the prevalence of CRN was 37.3% among disabled beneficiaries with >= 3 morbidities as compared with 28.1% among those with fewer morbidities; for spending less on basic needs, the prevalence was 25.4% versus 15.7%, respectively. There were no statistically detectable changes in either measure when comparing 2011 with 2007. CONCLUSIONS: Disabled Medicare beneficiaries continue to struggle to afford prescription medications. There is an urgent need for focused policy attention on this vulnerable population, which has inadequate financial access to drug treatments, despite having drug coverage under Medicare Part D. PMID- 25122531 TI - The ecological fallacy of the role of age in chronic disease and hospital demand. AB - OBJECTIVE: To examine the relationship between age and all-cause hospital utilization in the years preceding and following a diagnosis in hospital of heart failure, type 2 diabetes, or chronic obstructive pulmonary disease (COPD). RESEARCH DESIGN: A cohort study of all patients in Western Australia who have had a principal diagnosis of heart failure, type 2 diabetes, or COPD, upon admission to hospital. All-cause hospital utilization 6 years preceding and 4 years following cardinal events, that is, a disease-specific diagnosis upon hospital admission, where such an event has not occurred in the previous 2 years, are examined in specific age groups. RESULTS: Six years preceding a cardinal event, all-cause emergency department (ED) presentations are similar in all age groups, from under 55 to over 85 years of age, except in COPD where ED presentation rates are higher in younger groups. All-cause hospital inpatient days are transiently higher in the years preceding and following a cardinal event in older age groups, yet return to similar levels across all age cohorts after 4 years. ED presentations are significantly higher in the 4 years following cardinal events in younger compared with older groups. CONCLUSIONS: Longitudinal analysis of utilization around cardinal events overcomes the confounding effect of differences in chronic disease rates between age groups, avoiding a source of ecologic bias that erroneously attributes increasing utilization in individuals with chronic disease to age. Programs designed to reduce hospital demand in patients with chronic disease should possibly focus on younger, rather than older, individuals. PMID- 25122532 TI - Comb-push ultrasound shear elastography (CUSE) for evaluation of thyroid nodules: preliminary in vivo results. AB - In clinical practice, an overwhelming majority of biopsied thyroid nodules are benign. Therefore, there is a need for a complementary and noninvasive imaging tool to provide clinically relevant diagnostic information about thyroid nodules to reduce the rate of unnecessary biopsies. The goal of this study was to evaluate the feasibility of utilizing comb-push ultrasound shear elastography (CUSE) to measure the mechanical properties (i.e., stiffness) of thyroid nodules and use this information to help classify nodules as benign or malignant. CUSE is a fast and robust 2-D shear elastography technique in which multiple laterally distributed acoustic radiation force beams are utilized simultaneously to produce shear waves. Unlike other shear elasticity imaging modalities, CUSE does not suffer from limited field of view (FOV) due to shear wave attenuation and can provide a large FOV at high frame rates. To evaluate the utility of CUSE in thyroid imaging, a preliminary study was performed on a group of five healthy volunteers and 10 patients with ultrasound-detected thyroid nodules prior to fine needle aspiration biopsy. The measured shear wave speeds in normal thyroid tissue and thyroid nodules were converted to Young's modulus (E), indicating a measure of tissue stiffness. Our results indicate an increase in E for thyroid nodules compared to normal thyroid tissue. This increase was significantly higher in malignant nodules compared to benign. The Young's modulus in normal thyroid tissue, benign and malignant nodules were found to be 23.2 +/-8.29 kPa, 91.2+/ 34.8 kPa, and 173.0+/-17.1 kPa, respectively. Results of this study suggest the utility of CUSE in differentiating between benign and malignant thyroid nodules. PMID- 25122533 TI - Design, synthesis, and biological evaluation of stable colchicine binding site tubulin inhibitors as potential anticancer agents. AB - To block the metabolically labile sites of novel tubulin inhibitors targeting the colchicine binding site based on SMART, ABI, and PAT templates, we have designed, synthesized, and biologically tested three focused sets of new derivatives with modifications at the carbonyl linker, the para-position in the C ring of SMART template, and modification of A ring of the PAT template. Structure-activity relationships of these compounds led to the identification of new benzimidazole and imidazo[4,5-c]pyridine-fused ring templates, represented by compounds 4 and 7, respectively, which showed enhanced antitumor activity and substantially improved the metabolic stability in liver microsomes compared to SMART. MOM group replaced TMP C ring and generated a potent analogue 15, which showed comparable potency to the parent SMART compound. Further modification of PAT template yielded another potent analogue 33 with 5-indolyl substituent at A ring. PMID- 25122534 TI - Monolithic gyroidal mesoporous mixed titanium-niobium nitrides. AB - Mesoporous transition metal nitrides are interesting materials for energy conversion and storage applications due to their conductivity and durability. We present ordered mixed titanium-niobium (8:2, 1:1) nitrides with gyroidal network structures synthesized from triblock terpolymer structure-directed mixed oxides. The materials retain both macroscopic integrity and mesoscale ordering despite heat treatment up to 600 degrees C, without a rigid carbon framework as a support. Furthermore, the gyroidal lattice parameters were varied by changing polymer molar mass. This synthesis strategy may prove useful in generating a variety of monolithic ordered mesoporous mixed oxides and nitrides for electrode and catalyst materials. PMID- 25122535 TI - Bias voltage induced resistance switching effect in single-molecule magnets' tunneling junction. AB - An electric-pulse-induced reversible resistance change effect in a molecular magnetic tunneling junction, consisting of a single-molecule magnet (SMM) sandwiched in one nonmagnetic and one ferromagnetic electrode, is theoretically investigated. By applying a time-varying bias voltage, the SMM's spin orientation can be manipulated with large bias voltage pulses. Moreover, the different magnetic configuration at high-resistance/low-resistance states can be 'read out' by utilizing relative low bias voltage. This device scheme can be implemented with current technologies (Khajetoorians et al 2013 Science 339 55) and has potential application in molecular spintronics and high-density nonvolatile memory devices. PMID- 25122537 TI - Postoperative neurocognitive dysfunction in elderly patients after xenon versus propofol anesthesia for major noncardiac surgery: a double-blinded randomized controlled pilot study: retraction. PMID- 25122536 TI - Evaluation of the Macular Choroidal Thickness Using Spectral Optical Coherence Tomography in Pseudoexfoliation Glaucoma. AB - PURPOSE: To evaluate the choroidal thickness (CT) in pseudoexfoliative (PEX) glaucoma and age-matched healthy subjects using spectral optical coherence tomography (SD-OCT). PATIENTS AND METHODS: In this prospective study, 32 eyes of 32 PEX glaucoma patients and 30 eyes of 30 age-matched healthy subjects were enrolled. The CT is measured perpendicularly (from the outer edge of the hyperreflective retinal pigment epithelium to the inner sclera) at the fovea, and 1.5 mm temporal, 3.0 mm temporal, 1.5 mm nasal, and 3.0 mm nasal to the fovea using SD-OCT (RTVue-100). RESULTS: The groups were similar regarding the mean age and axial length values (both, P>0.05). The CT measurements were 182.12 +/- 39.88 and 201.56 +/- 32.00 MUm at 1.5 mm nasal to the fovea (P=0.039), and 126.47 +/- 32.12 and 146.60 +/- 31.37 MUm at 3.0 mm nasal to the fovea (P=0.015) in the PEX glaucoma and control groups, respectively. There were no significant differences in the subfoveal and temporal CT measurements among the 2 groups (all, P>0.05). CONCLUSIONS: The findings of this study indicate that PEX glaucoma causes significant thinning in the nasal choroid. Thus, measuring the CT with SD-OCT may be the way of better clarification of the relationship between PEX and glaucomatous optic neuropathy. PMID- 25122538 TI - Fungal natural products in research and development. AB - To date approximately 100 000 fungal species are known although far more than one million are expected. The variety of species and the diversity of their habitats, some of them less exploited, allow the conclusion that fungi continue to be a rich source of new metabolites. Besides the conventional fungal isolates, an increasing interest in endophytic and in marine-derived fungi has been noticed. In addition new screening strategies based on innovative chemical, biological, and genetic approaches have led to novel fungal metabolites in recent years. The present review focuses on new fungal natural products published from 2009 to 2013 highlighting the originality of the structures and their biological potential. Furthermore synthetic products based on fungal metabolites as well as new developments in the uses or the biological activity of known compounds or new derivatives are discussed. PMID- 25122540 TI - Nanoparticle size detection limits by single particle ICP-MS for 40 elements. AB - The quantification and characterization of natural, engineered, and incidental nano- to micro-size particles are beneficial to assessing a nanomaterial's performance in manufacturing, their fate and transport in the environment, and their potential risk to human health. Single particle inductively coupled plasma mass spectrometry (spICP-MS) can sensitively quantify the amount and size distribution of metallic nanoparticles suspended in aqueous matrices. To accurately obtain the nanoparticle size distribution, it is critical to have knowledge of the size detection limit (denoted as Dmin) using spICP-MS for a wide range of elements (other than a few available assessed ones) that have been or will be synthesized into engineered nanoparticles. Herein is described a method to estimate the size detection limit using spICP-MS and then apply it to nanoparticles composed of 40 different elements. The calculated Dmin values correspond well for a few of the elements with their detectable sizes that are available in the literature. Assuming each nanoparticle sample is composed of one element, Dmin values vary substantially among the 40 elements: Ta, U, Ir, Rh, Th, Ce, and Hf showed the lowest Dmin values, <=10 nm; Bi, W, In, Pb, Pt, Ag, Au, Tl, Pd, Y, Ru, Cd, and Sb had Dmin in the range of 11-20 nm; Dmin values of Co, Sr, Sn, Zr, Ba, Te, Mo, Ni, V, Cu, Cr, Mg, Zn, Fe, Al, Li, and Ti were located at 21 80 nm; and Se, Ca, and Si showed high Dmin values, greater than 200 nm. A range of parameters that influence the Dmin, such as instrument sensitivity, nanoparticle density, and background noise, is demonstrated. It is observed that, when the background noise is low, the instrument sensitivity and nanoparticle density dominate the Dmin significantly. Approaches for reducing the Dmin, e.g., collision cell technology (CCT) and analyte isotope selection, are also discussed. To validate the Dmin estimation approach, size distributions for three engineered nanoparticle samples were obtained using spICP-MS. The use of this methodology confirms that the observed minimum detectable sizes are consistent with the calculated Dmin values. Overall, this work identifies the elements and nanoparticles to which current spICP-MS approaches can be applied, in order to enable quantification of very small nanoparticles at low concentrations in aqueous media. PMID- 25122541 TI - High open circuit voltage in regioregular narrow band gap polymer solar cells. AB - The regioregular narrow band gap (E(g) ~1.5 eV) conjugated polymer PIPCP was designed and synthesized. PIPCP contains a backbone comprised of CPDT-PT-IDT-PT repeat units (CPDT = cyclopentadithiophene, PT = pyridyl[2,1,3]thiadiazole, IDT = indacenodithiophene) and strictly organized PT orientations, such that the pyridyl N-atoms point toward the CPDT fragment. Comparison of PIPCP with the regiorandom counterpart PIPC-RA illustrates that the higher level of molecular order translates to higher power conversion efficiencies (PCEs) when incorporated into bulk heterojunction (BHJ) organic solar cells. Examination of thin films via absorption spectroscopy and grazing incidence wide-angle X-ray diffraction (GIWAXS) experiments provides evidence of higher order within thin films obtained by spin coating. Most significantly, we find that PIPCP:PC61BM blends yield devices with an open circuit voltage (V(oc)) of 0.86 V, while maintaining a PCE of ~6%. Comparison against a wide range of analogous narrow band gap conjugated polymers reveals that this V(oc) value is particularly high for a BHJ system with band gaps in the 1.4-1.5 eV range thereby indicating a very low E(g) - eV(oc) loss. PMID- 25122542 TI - Systematic variation of gel-phase texture in phospholipid membranes. AB - The tilted gel phase of lipid bilayers can display in-plane orientational texture due to long-range alignment of the molecular director. We explore systematic variations of texture defects in a series of binary phospholipid membranes. Using polarized two-photon fluorescence microscopy, the texture pattern of single domains is revealed. The appearance of a central vortex-type defect in each domain correlates with a particular range of hydrophobic mismatch values h > 1 nm at the domain border while domains with h < 1 nm correlate with uniformly aligned texture. The central vortex defect is characterized by a defect angle, indicating its bend or splay nature. Using image analysis, we measure the defect angle and find that it has primarily bend character for small mismatch values (h ~ 1 nm) and primarily splay nature for larger values of h. For domains containing a vortex, the domain shape is decoupled from the texture while for uniformly textured domains there is a preferred texture orientation of ?45 degrees along the domain border. The results establish a foundation for understanding texture phenomena in compositionally complex membranes. PMID- 25122539 TI - Patterns of admixture and population structure in native populations of Northwest North America. AB - The initial contact of European populations with indigenous populations of the Americas produced diverse admixture processes across North, Central, and South America. Recent studies have examined the genetic structure of indigenous populations of Latin America and the Caribbean and their admixed descendants, reporting on the genomic impact of the history of admixture with colonizing populations of European and African ancestry. However, relatively little genomic research has been conducted on admixture in indigenous North American populations. In this study, we analyze genomic data at 475,109 single-nucleotide polymorphisms sampled in indigenous peoples of the Pacific Northwest in British Columbia and Southeast Alaska, populations with a well-documented history of contact with European and Asian traders, fishermen, and contract laborers. We find that the indigenous populations of the Pacific Northwest have higher gene diversity than Latin American indigenous populations. Among the Pacific Northwest populations, interior groups provide more evidence for East Asian admixture, whereas coastal groups have higher levels of European admixture. In contrast with many Latin American indigenous populations, the variance of admixture is high in each of the Pacific Northwest indigenous populations, as expected for recent and ongoing admixture processes. The results reveal some similarities but notable differences between admixture patterns in the Pacific Northwest and those in Latin America, contributing to a more detailed understanding of the genomic consequences of European colonization events throughout the Americas. PMID- 25122543 TI - Marked anti-tumor effects of CD8(+)CD62L(+) T cells from melanoma-bearing mice. AB - CD8(+)CD62L(+) T cells have been shown to play pivotal roles in anti-viral immunity, chronic myeloid leukemia and renal cell carcinoma. Recently, CD8(+)CD62L(+) T cells from naive mice (nCD8(+)CD62L(+) T cells) have shown superior anti-tumor properties in melanoma-bearing mice. Considering that antigen specific memory T cells have shown to possess more potent immunity than non specific memory T cells, we hypothesized that CD8(+)CD62L(+) T cells from tumor bearing individuals (mCD8(+)CD62L(+) T cells) might have superior anti-tumor effect than nCD8(+)CD62L(+) T cells. Therefore, we investigated phenotypes, functions and the in vivo distribution of mCD8(+)CD62L(+) T cells in tumor bearing mice. We found that, while keeping the features of central memory T cells, the frequency of mCD8(+)CD62L(+) T cell in the spleen of tumor-bearing mice was significantly higher than that the one of nCD8(+)CD62L(+) T cell in naive mice. Moreover, we demonstrated that mCD8(+)CD62L(+) T cells had higher proliferation rate and IFN-gamma production than nCD8(+)CD62L(+) T cells, in vitro. We performed adoptive transfer of mCD8(+)CD62L(+) T cells into melanoma bearing mice and tracked them in spleen, lymph nodes and in melanoma tissues. Our results show that mCD8(+)CD62L(+) T cells had stronger in vivo anti-tumoral activity than nCD8(+)CD62L(+) T cells. This study highlights the therapeutic potential of mCD8(+)CD62L(+) T cells in the immunotherapy of melanoma and possibly other tumors. PMID- 25122545 TI - Italy between drinking culture and control policies for alcoholic beverages. AB - This paper focuses on whether the on-going dramatic decrease in alcohol consumption in Italy, especially of wine, during 1961-2008, was associated with which parallel sociodemographic and economic changes and with alcohol control policies. The study, using both time series (TS) and artificial neural network (ANN)-based analyses documents that its selected sociodemographic and economic factors, and particularly urbanization, had a definite connection with wine consumption decrease, spirits decrease, and the increase in beer consumption over time. On the other hand, control policies showed no effect on the decline in alcohol consumption, since no alcohol control policy existed in Italy between 1960 and 1987. A few policies introduced since 1988 (BAC and sale restrictions during mass events) may have contributed to reducing or to maintaining the on going reduction. Study limitations are noted and future needed research is suggested. PMID- 25122546 TI - Asymmetrical distribution of choline phospholipids revealed by click chemistry and freeze-fracture electron microscopy. AB - Choline-containing phospholipids (Cho-PLs) are major components of all cellular membranes. We developed an electron microscopic technique to investigate the poorly understood problem of how Cho-PLs are distributed between membrane leaflets. Our method relies on generating freeze-fracture replicas of cells metabolically labeled with the choline analog, propargylcholine, followed by "click" reaction to conjugate biotin to propargylcholine head groups, and immunodetection of biotin with colloidal gold. Using this method in budding yeast, we found that, surprisingly, the Golgi and plasma membrane display a cytoplasmic leaflet-dominant asymmetry in Cho-PL distribution; in contrast, Cho PLs are evenly distributed between the exoplasmic and cytoplasmic leaflets of other organelle membranes. In mammalian culture cells, the plasma membrane shows symmetrical Cho-PL distribution between leaflets, suggesting a fundamental difference between yeast and mammals. Our method should be expandable to other classes of lipids and will be useful for deciphering the mechanism responsible for generating lipid asymmetry in biological membranes. PMID- 25122547 TI - Evaluation of chirp reversal power modulation sequence for contrast agent imaging. AB - Over the last decade, significant research effort has been focused on the use of chirp for contrast agent imaging because chirps are known to significantly increase imaging contrast-to-noise ratio (CNR). New imaging schemes, such as chirp reversal (CR), have been developed to improve contrast detection by increasing non-linear microbubble responses. In this study we evaluated the contrast enhancement efficiency of various chirped imaging sequences in combination with well-established imaging schemes such as power modulation (PM) and pulse inversion (PI). The imaging schemes tested were implemented on a fully programmable open scanner and evaluated by ultrasonically scanning (excitation frequency of 2.5 MHz; amplitude of 350 kPa) a tissue-mimicking flow phantom comprising a 4 mm diameter tube through which aqueous dispersions (dilution fraction of 1/2000) of the commercial ultrasound contrast agent, SonoVue((r)) were continuously circulated. The recovery of non-linear microbubble responses after chirp compression requires the development and the optimization of a specific filter. A compression filter was therefore designed and used to compress and extract several non-linear components from the received microbubble responses. The results showed that using chirps increased the image CNR by approximately 10 dB, as compared to conventional Gaussian apodized sine burst excitation but degraded the axial resolution by a factor of 1.4, at -3 dB. We demonstrated that the highest CNR and contrast-to-noise ratio (CTR) were achievable when CR was combined with PM as compared to other imaging schemes such as PI. PMID- 25122544 TI - Cyclotorsional and non-cyclotorsional components of eye rotation observed from sitting to supine position. AB - PURPOSE: Evaluate average cyclotorsional and non-cyclotorsional components (NCY) of eye rotation from sitting to supine, and associate average cyclotorsion to different variables. METHODS: Medical records of patients who underwent bilateral sequential laser refractive surgery were retrospectively evaluated. Recorded variables included the patient's age, refraction, automated keratometry, pupil displacement and eye rotation from sitting to supine position. Measured iris rotation (total rotation, TR) was decomposed into two components: NCY, defined as the common rotation component of each eye of the same patient, and cyclotorsional component (CY), defined as the assumed independent eye rotation for each eye in relation to the face, so that TR=NCY+CY. Cyclotorsion ratio (CR) was calculated as CR=|CY|/|TR|, and used to correlate CY with TR for each eye. RESULTS: Data from 310 eyes of 155 patients were evaluated. TR was +1.43 degrees +/-3.41 degrees (-8.30 degrees to +9.20 degrees ). Average CYs and NCYs per patient were +1.43 degrees +/-2.04 degrees (-3.15+/- to +7.40 degrees ) and -0.28 degrees +/-2.72 degrees (-6.85 degrees to +7.15 degrees ), respectively. TR demonstrated that 40.6% and 8.4% of patients presented bilateral excyclotorsion and incyclotorsion, respectively. When excluding NCYs, average CYs demonstrated that 74.2% of patients presented excyclotorsion and 23.9% presented incyclotorsion. CR demonstrated that TR represented from 75% to 125% of average CY in 19.68% of the eyes. TR overestimated and underestimated average CYs above these limits in 52.26% and 28.06% of the eyes, respectively. There was no statistical association between average CYs and the different variables. DISCUSSION: This study demonstrates that most of the rotations previously attributed to torsional components were probably due to NCYs, such as postural misalignments. Apparently, the amplitude of cyclotorsional movements is smaller than observed in previous reports, and could not be associated with any studied variable. PMID- 25122548 TI - Computed tomography-guided C2 pedicle screw placement for treatment of unstable hangman fractures. AB - STUDY DESIGN: Case series and description of technique. OBJECTIVE: The purpose of this study was to evaluate the feasibility and accuracy of inserting pedicle screws in unstable Hangman fracture cases by using intraoperative CT (O-arm) based navigation. SUMMARY OF BACKGROUND DATA: Hangman fracture, also known as traumatic spondylolisthesis of the C2, is defined as a fracture involving the lamina, articular facets, pedicles, or pars of the axis vertebra. Opinions vary regarding the optimal treatment of unstable Hangman fractures. Some authors have recommended the use of rigid orthosis, whereas others have recommended surgical stabilization. The peculiar anatomy of the upper cervical spine is highly variable, and the presence of surrounding neurovascular structures makes pedicle screw fixation even more technically challenging. The advent of intraoperative 3 dimensional navigation systems permits safe and accurate instrumentation of the cervical spine. METHODS: Ten patients with unstable Hangman fracture, with age ranging from 17 years to 81 years, were operated under O-arm-based navigation, and screw position was confirmed with intraoperative computed tomographic scan. RESULTS: A total of 52 screws were inserted under O-arm guidance: 20 in C2 pedicle, 20 in C3 lateral mass, and rest in C4 lateral mass. Screw misplacement was seen in only 1 C2 pedicle screw (1 of 20, 5%). No new-onset neurological deficit developed in any of the patients. Follow-up ranged from 3 months to 21 months. Bony fusion was achieved in all. Full rotation was preserved at C1-C2 joint. All the patients (50%) with neurological deficits before surgery improved after surgery. CONCLUSION: This series demonstrates that C2 pedicle screws can be put with precision under O-arm-guided navigation, and intraoperative computed tomographic scan can confirm position of screws. Patients can be operated and mobilized early with negligible risk of screw misplacement, with preservation of motion at the C1-C2 joint. LEVEL OF EVIDENCE: 4. PMID- 25122551 TI - Prevalence and risk factors of respiratory symptoms among home-based garment workers in Bangkok, Thailand. AB - This study aimed to determine the prevalence and risk factors associated with respiratory symptoms. A cross-sectional study with random sampling method was employed and 300 home-based garment workers (HBGWs) were recruited. Risk factors, including personal factors; knowledge, health preventive behaviors, and skill of self-health surveillance, working condition, and respiratory symptoms were assessed. Data were collected using self-reported questionnaires. Prevalence of respiratory symptom was 22.3%. Majority of participants were female (78%). Mean age and working experience were 37.38 years (SD = 10.70) and 13.58 years (SD = 8.71), respectively. Allergic respiratory symptoms (odds ratio [OR] = 16.5; 95% confidence interval [CI] = 8.61-31.7) and garment dust exposure (OR = 12.3; 95% CI = 6.49-23.3) were significantly associated with respiratory symptoms (P < .001). Logistic regression analysis indicated history of allergic predicted the respiratory symptoms (OR = 12.96; 95% CI = 4.24-39.55). HBGWs who had serious allergic symptoms and high exposure to dust were at risk of respiratory symptoms. Therefore, preventive program for garment dust exposure among HBGWs is needed. PMID- 25122552 TI - Assessment of internalized stigma among patients with mental disorders in Thiruvananthapuram district, Kerala, India. AB - This study aims to compare the prevalence of high internalized stigma of mental illness among patients attending community-based and psychiatric hospital-based care in Thiruvananthapuram district, Kerala, India and to examine the factors associated with high internalized stigma. A cross-sectional survey was conducted among 290 patients, mean age 45 years, 38.2% and 61.8% female. A Malayalam version of the Internalized Stigma of Mental Illness inventory was used for assessing internalized stigma. A multistage random sampling method was adopted. The prevalence of high internalized stigma was higher among patients from community-based care (44.7%) as compared with those from psychiatric hospital based care (34.1%). Apart from treatment in community-based care, age <= 45 years, unemployment, absence of long-term friendships, no hope of cure with medication, presence of other illnesses, and substance use were significantly associated with high internalized stigma. More than one third of the subjects had high internalized stigma. PMID- 25122550 TI - Cooperativity to increase Turing pattern space for synthetic biology. AB - It is hard to bridge the gap between mathematical formulations and biological implementations of Turing patterns, yet this is necessary for both understanding and engineering these networks with synthetic biology approaches. Here, we model a reaction-diffusion system with two morphogens in a monostable regime, inspired by components that we recently described in a synthetic biology study in mammalian cells.1 The model employs a single promoter to express both the activator and inhibitor genes and produces Turing patterns over large regions of parameter space, using biologically interpretable Hill function reactions. We applied a stability analysis and identified rules for choosing biologically tunable parameter relationships to increase the likelihood of successful patterning. We show how to control Turing pattern sizes and time evolution by manipulating the values for production and degradation relationships. More importantly, our analysis predicts that steep dose-response functions arising from cooperativity are mandatory for Turing patterns. Greater steepness increases parameter space and even reduces the requirement for differential diffusion between activator and inhibitor. These results demonstrate some of the limitations of linear scenarios for reaction-diffusion systems and will help to guide projects to engineer synthetic Turing patterns. PMID- 25122554 TI - Matrix metalloproteinase 9-mediated shedding of syndecan 4 in response to tumor necrosis factor alpha: a contributor to endothelial cell glycocalyx dysfunction. AB - The endothelial surface glycocalyx is a hydrated mesh in which proteoglycans are prominent. It is damaged in diseases associated with elevated levels of tumor necrosis factor alpha (TNF-alpha). We investigated the mechanism of TNF-alpha induced disruption of the glomerular endothelial glycocalyx. We used conditionally immortalized human glomerular endothelial cells (GEnCs), quantitative PCR arrays, Western blotting, immunoprecipitation, immunofluorescence, and dot blots to examine the effects of TNF-alpha. TNF-alpha induced syndecan 4 (SDC4) mRNA up-regulation by 2.5-fold, whereas cell surface SDC4 and heparan sulfate (HS) were reduced by 36 and 30%, respectively, and SDC4 and sulfated glycosaminoglycan in the culture medium were increased by 52 and 65%, respectively, indicating TNF-alpha-induced shedding. Small interfering (siRNA) knockdown of SDC4 (by 52%) caused a corresponding loss of cell surface HS of similar magnitude (38%), and immunoprecipitation demonstrated that SDC4 and HS are shed as intact proteoglycan ectodomains. All of the effects of TNF-alpha on SDC4 and HS were abrogated by the metalloproteinase (MMP) inhibitor batimastat. Also abrogated was the associated 37% increase in albumin passage across GEnC monolayers. Specific MMP9 knockdown by siRNA similarly blocked TNF-alpha effects. SDC4 is the predominant HS proteoglycan in the GEnC glycocalyx. TNF-alpha-induced MMP9-mediated shedding of SDC4 is likely to contribute to the endothelial glycocalyx disruption observed in diabetes and inflammatory states. PMID- 25122553 TI - Activation of EPAC1/2 is essential for osteoclast formation by modulating NFkappaB nuclear translocation and actin cytoskeleton rearrangements. AB - Bisphosphonates inhibit osteoclast differentiation/function via inhibition of Rap1A isoprenylation. As Rap1 is the effector of exchange protein directly activated by cAMP (EPAC) proteins, we determined the role of EPAC in osteoclast differentiation. We examined osteoclast differentiation as the number of primary murine/human bone-marrow precursors that differentiated into multinucleated TRAP positive cells in the presence of EPAC-selective stimulus (8-pCTP-2'-O-Me-cAMP, 100 MUM; 8-pCTP-2'-O-Me-cAMP-AM, 1 MUM) or inhibitor brefeldin A (BFA), ESI-05, and ESI-09 (10 MUM each). Rap1 activity was assessed, and signaling events, as well as differentiation in EPAC1/2-knockdown RAW264.7 cells, were studied. Direct EPAC1/2 stimulation significantly increased osteoclast differentiation, whereas EPAC1/2 inhibition diminished differentiation (113 +/- 6%, P < 0.05, and 42 +/- 10%, P < 0.001, of basal, respectively). Rap1 activation was maximal 15 min after RANKL stimulation (147 +/- 9% of basal, P < 0.001), whereas silencing of EPAC1/2 diminished activated Rap1 (43 +/- 13 and 20 +/- 15% of control, P < 0.001) and NFkB nuclear translocation. TRAP-staining revealed no osteoclast differentiation in EPAC1/2-KO cells. Cathepsin K, NFATc1, and osteopontin mRNA expression decreased in EPAC1/2-KO cells when compared to control. RhoA, cdc42, Rac1, and FAK were activated in an EPAC1/2-dependent manner, and there was diminished cytoskeletal assembly in EPAC1/2-KO cells. In summary, EPAC1 and EPAC2 are critical signaling intermediates in osteoclast differentiation that permit RANKL stimulated NFkB nuclear translocation and actin rearrangements. Targeting this signaling intermediate may diminish bone destruction in inflammatory arthritis. PMID- 25122555 TI - Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers Danlos syndrome from benign joint hypermobility syndrome in patients. AB - There is a clinical overlap between classic Ehlers-Danlos syndrome (cEDS) and benign joint hypermobility syndrome (BJHS), with hypermobility as the main symptom. The purpose of this study was to investigate the role of type V collagen mutations and tendon pathology in these 2 syndromes. In patients (cEDS, n=7; BJHS, n=8) and controls (Ctrl, n=8), we measured patellar tendon ultrastructure (transmission electron microscopy), dimensions (magnetic resonance imaging), and biomechanical properties (force and ultrasonographic measurements during a ramped isometric knee extension). Mutation analyses (COL5A1 and COL5A2) were performed in the patients. COL5A1 mutations were found in 3 of 4 of the patients with cEDS. Patellar tendon dimensions were similar between the groups, but large, irregular collagen fibrils were in 4 of 5 patients with cEDS. In the cEDS group, tendon stiffness and Young's modulus were reduced to ~50% of that in BJHS and Ctrl groups (P<0.05). The nonhypermobile, healthy controls were matched with the patients in age, sex, body weight, and physical activity, to compare outcomes. COL5A1 mutations led to structural tendon pathology and low tendon stiffness in cEDS, explaining the patients' hypermobility, whereas no tendon pathology was found that explained the hypermobility in BJHS. PMID- 25122557 TI - Disuse deterioration of human skeletal muscle challenged by resistive exercise superimposed with vibration: evidence from structural and proteomic analysis. AB - In the present bed rest (BR) study, 23 volunteers were randomized into 3 subgroups: 60 d BR control (Ctr); BR with resistive exercise (RE; lower-limb load); and resistive vibration exercise (RVE; RE with superimposed vibration). The aim was to analyze by confocal and electron microscopy the effects of vibration on myofibril and filament integrity in soleus (Sol) and vastus lateralis (VL) muscle; differential proteomics of contractile, cytoskeletal, and costameric proteins (TN-C, ROCK1, and FAK); and expression of PGC1alpha and atrophy-related master genes MuRF1 and MuRF2. RVE (but not RE) preserved myofiber size and phenotype in Sol and VL by overexpressing MYBPC1 (42%, P <= 0.01), WDR1 (39%, P <= 0.01), sarcosin (84%, P <= 0.01), and CKM (20%, P <= 0.01) and prevented myofibrillar ultrastructural damage as detectable by MuRF1 expression. In Sol, cytoskeletal and contractile proteins were normalized by RVE, and TN-C increased (59%, P <= 0.01); the latter also with RE (108%, P <= 0.01). In VL, the outcomes of both RVE (acting on sarcosin and desmin) and RE (by way of troponinT slow and MYL2) were similar. RVE appears to be a highly efficient countermeasure protocol against muscle atrophy and ultrastructural and molecular dysregulation induced by chronic disuse. PMID- 25122556 TI - Long-acting antituberculous therapeutic nanoparticles target macrophage endosomes. AB - Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 MUg/10(6) cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 MUg/10(6) cells for native drugs. High RIF and INHP levels were retained in MDM for >15 d following nanoparticle loading. Rapid loss of native drugs was observed in cells and culture fluids within 24 h. Antimicrobial activities were determined against Mycobacterium smegmatis (M. smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs. Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments. These were the same compartments that contained the pathogen. Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens. PMID- 25122559 TI - Fixing the troubled mental health system. PMID- 25122560 TI - The community care chest is running out of cards. PMID- 25122561 TI - Introducing the foundation Chair of the new Division of Ecoimmunology and Disease Ecology. PMID- 25122558 TI - Protective role of macrophage migration inhibitory factor in nonalcoholic steatohepatitis. AB - MIF is an inflammatory cytokine but is hepatoprotective in models of hepatotoxin induced liver fibrosis. Hepatic fibrosis can also develop from metabolic liver disease, such as nonalcoholic fatty liver disease (NASH). We investigated the role of MIF in high-fat or methionine- and choline-deficient diet mouse models of NASH. Mif(-/-) mice showed elevated liver triglyceride levels (WT, 53+/-14 mg/g liver; Mif(-/-), 103+/-7 mg/g liver; P<0.05) and a 2-3-fold increased expression of lipogenic genes. Increased fatty degeneration in the livers of Mif(-/-) mice was associated with increased hepatic inflammatory cells (1.6-fold increase in F4/80(+) macrophages) and proinflammatory cytokines (e.g., 2.3-fold increase in Tnf-alpha and 2-fold increase in Il-6 expression). However, inflammatory cells and cytokines were decreased by 50-90% in white adipose tissue (WAT) of Mif(-/-) mice. Subset analysis showed that macrophage phenotypes in livers of Mif(-/-) mice were skewed toward M2 (e.g., 1.7-fold and 2.5-fold increase in Arg1 and Il 13, respectively, and 2.5-fold decrease in iNos), whereas macrophages were generally reduced in WAT of these mice (70% reduction in mRNA expression of F4/80(+) macrophages). The protective MIF effect was scrutinized in isolated hepatocytes. MIF reversed inflammation-induced triglyceride accumulation in Hepa1 6 cells and primary hepatocytes and also attenuated oleic acid-elicited triglyceride increase in 3T3-L1 adipocytes. Protection from fatty hepatocyte degeneration was paralleled by a 2- to 3-fold reduction by MIF of hepatocyte proinflammatory cytokine production. Blockade of MIF receptor cluster of differentiation 74 (CD74) but not of CXCR2 or CXCR4 fully reverted the protective effect of MIF, comparable to AMPK inhibition. In summary, we demonstrate that MIF mediates hepatoprotection through the CD74/AMPK pathway in hepatocytes in metabolic models of liver injury. PMID- 25122562 TI - Small primary care physician practices have low rates of preventable hospital admissions. AB - Nearly two-thirds of US office-based physicians work in practices of fewer than seven physicians. It is often assumed that larger practices provide better care, although there is little evidence for or against this assumption. What is the relationship between practice size--and other practice characteristics, such as ownership or use of medical home processes--and the quality of care? We conducted a national survey of 1,045 primary care-based practices with nineteen or fewer physicians to determine practice characteristics. We used Medicare data to calculate practices' rate of potentially preventable hospital admissions (ambulatory care-sensitive admissions). Compared to practices with 10-19 physicians, practices with 1-2 physicians had 33 percent fewer preventable admissions, and practices with 3-9 physicians had 27 percent fewer. Physician owned practices had fewer preventable admissions than hospital-owned practices. In an era when health care reform appears to be driving physicians into larger organizations, it is important to measure the comparative performance of practices of all sizes, to learn more about how small practices provide patient care, and to learn more about the types of organizational structures--such as independent practice associations--that may make it possible for small practices to share resources that are useful for improving the quality of care. PMID- 25122563 TI - Different phase behavior and packing of ceramides with long (C16) and very long (C24) acyls in model membranes: infrared spectroscopy using deuterated lipids. AB - Ceramides (Cer) are the central molecules in sphingolipid metabolism that participate in cellular signaling and also prevent excessive water loss by the skin. Previous studies showed that sphingosine-based Cer with a long 16C chain (CerNS16) and very long 24C-chain ceramides (CerNS24) differ in their biological actions. Increased levels of long CerNS16 at the expense of the very long CerNS24 have been found in atopic dermatitis patients, and this change correlated with the skin barrier properties. To probe the membrane behavior of the long CerNS16 and the very long chain CerNS24, we studied their interactions with fatty acids and cholesterol in model stratum corneum membranes using infrared spectroscopy. Using Cer with deuterated acyls and/or deuterated fatty acids, we showed differences in lipid mixing, packing, and thermotropic phase behavior between long and very long Cer. These differences were observed in the presence of lignoceric acid or a heterogeneous fatty acid mixture (C16-C24), in the presence or absence of cholesterol sulfate, and at 5-95% humidity. In these membranes, very long CerNS24 prefers an extended (splayed-chain) conformation in which the fatty acid is associated with the very long Cer chain. In contrast, the shorter CerNS16 and fatty acids are mostly phase separated. PMID- 25122564 TI - Pharmacokinetic modeling of the subcutaneous absorption of therapeutic proteins. AB - Subcutaneous injection is an important route of administration for therapeutic proteins that provides several advantages over other modes of parenteral delivery. Despite extensive clinical use, the exact mechanism underlying subcutaneous absorption of proteins is not completely understood, and the accuracy of prediction of absorption of biotherapeutics in humans remains unsatisfactory. This review summarizes a variety of models that have been developed for describing the pharmacokinetics of therapeutic proteins administered by subcutaneous injection, including single- and dual-pathway absorption models. Modeling of the lymphatic uptake and redistribution, absorption of monoclonal antibodies and insulin, and population analysis of protein absorption are discussed. The review also addresses interspecies modeling and prediction of absorption in humans, highlights important factors affecting the absorption processes, and suggests approaches for future development of mechanism-based absorption models. PMID- 25122566 TI - Joint removal of random and fixed-pattern noise through spatiotemporal video filtering. AB - We propose a framework for the denoising of videos jointly corrupted by spatially correlated (i.e., nonwhite) random noise and spatially correlated fixed-pattern noise. Our approach is based on motion-compensated 3D spatiotemporal volumes, i.e., a sequence of 2D square patches extracted along the motion trajectories of the noisy video. First, the spatial and temporal correlations within each volume are leveraged to sparsify the data in 3D spatiotemporal transform domain, and then the coefficients of the 3D volume spectrum are shrunk using an adaptive 3D threshold array. Such array depends on the particular motion trajectory of the volume, the individual power spectral densities of the random and fixed-pattern noise, and also the noise variances which are adaptively estimated in transform domain. Experimental results on both synthetically corrupted data and real infrared videos demonstrate a superior suppression of the random and fixed pattern noise from both an objective and a subjective point of view. PMID- 25122565 TI - In vitro assay of six UDP-glucuronosyltransferase isoforms in human liver microsomes, using cocktails of probe substrates and liquid chromatography-tandem mass spectrometry. AB - UDP-glucuronosyltransferase (UGT)-mediated drug-drug interactions are commonly evaluated during drug development. We present a validated method for the simultaneous evaluation of drug-mediated inhibition of six major UGT isoforms, developed in human liver microsomes through the use of pooled specific UGT probe substrates (cocktail assay) and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The six probe substrates used in this assay were estradiol (UGT1A1), chenodeoxycholic acid (UGT1A3), trifluoperazine (UGT1A4), 4-hydroxyindole (UGT1A6), propofol (UGT1A9), and naloxone (UGT2B7). In a cocktail incubation, UGT1A1, UGT1A9, and UGT2B7 activities were substantially inhibited by other substrates. This interference could be eliminated by dividing substrates into two incubations: one containing estradiol, trifluoperazine, and 4 hydroxyindole, and the other containing chenodeoxycholic acid, propofol, and naloxone. Incubation mixtures were pooled for the simultaneous analysis of glucuronyl conjugates in a single LC-MS/MS run. The optimized cocktail method was further validated against single-probe substrate assays using compounds known to inhibit UGTs. The degree of inhibition of UGT isoform activities by such known inhibitors in this cocktail assay was not substantially different from that in single-probe assays. This six-isoform cocktail assay may be very useful in assessing the UGT-based drug-interaction potential of candidates in a drug discovery setting. PMID- 25122567 TI - Incremental N-mode SVD for large-scale multilinear generative models. AB - Tensor decomposition is frequently used in image processing and machine learning for its ability to express higher order characteristics of data. Among tensor decomposition methods, N-mode singular value decomposition (SVD) is widely used owing to its simplicity. However, the data dimension often becomes too large to perform N-mode SVD directly due to memory limitation. An incremental method to N mode SVD can be used to resolve this issue, but existing approaches only provide a result, which is just enough to solve discriminative problems, not the full factorization result. In this paper, we present a complete derivation of the incremental N-mode SVD, which can be applied to generative models, accompanied by a technique that can reduce the computational cost by reordering calculations. The proposed incremental N-mode SVD can also be used effectively to update the current result of N-mode SVD when new training data is received. The proposed method provides a very good approximation of N -mode SVD for the experimental data, and requires much less computation in updating a multilinear model. PMID- 25122568 TI - A novel video dataset for change detection benchmarking. AB - Change detection is one of the most commonly encountered low-level tasks in computer vision and video processing. A plethora of algorithms have been developed to date, yet no widely accepted, realistic, large-scale video data set exists for benchmarking different methods. Presented here is a unique change detection video data set consisting of nearly 90 000 frames in 31 video sequences representing six categories selected to cover a wide range of challenges in two modalities (color and thermal infrared). A distinguishing characteristic of this benchmark video data set is that each frame is meticulously annotated by hand for ground-truth foreground, background, and shadow area boundaries-an effort that goes much beyond a simple binary label denoting the presence of change. This enables objective and precise quantitative comparison and ranking of video-based change detection algorithms. This paper discusses various aspects of the new data set, quantitative performance metrics used, and comparative results for over two dozen change detection algorithms. It draws important conclusions on solved and remaining issues in change detection, and describes future challenges for the scientific community. The data set, evaluation tools, and algorithm rankings are available to the public on a website and will be updated with feedback from academia and industry in the future. PMID- 25122569 TI - DEB: definite error bounded tangent estimator for digital curves. AB - We propose a simple and fast method for tangent estimation of digital curves. This geometric-based method uses a small local region for tangent estimation and has a definite upper bound error for continuous as well as digital conics, i.e., circles, ellipses, parabolas, and hyperbolas. Explicit expressions of the upper bounds for continuous and digitized curves are derived, which can also be applied to nonconic curves. Our approach is benchmarked against 72 contemporary tangent estimation methods and demonstrates good performance for conic, nonconic, and noisy curves. In addition, we demonstrate a good multigrid and isotropic performance and low computational complexity of O(1) and better performance than most methods in terms of maximum and average errors in tangent computation for a large variety of digital curves. PMID- 25122570 TI - Interacting geometric priors for robust multimodel fitting. AB - Recent works on multimodel fitting are often formulated as an energy minimization task, where the energy function includes fitting error and regularization terms, such as low-level spatial smoothness and model complexity. In this paper, we introduce a novel energy with high-level geometric priors that consider interactions between geometric models, such that certain preferred model configurations may be induced.We argue that in many applications, such prior geometric properties are available and should be fruitfully exploited. For example, in surface fitting to point clouds, the building walls are usually either orthogonal or parallel to each other. Our proposed energy function is useful in dealing with unknown distributions of data errors and outliers, which are often the factors leading to biased estimation. Furthermore, the energy can be efficiently minimized using the expansion move method. We evaluate the performance on several vision applications using real data sets. Experimental results show that our method outperforms the state-of-the-art methods without significant increase in computation. PMID- 25122571 TI - Sharing visual secrets in single image random dot stereograms. AB - Visual cryptography schemes (VCSs) generate random and meaningless shares to share and protect secret images. Conventional VCSs suffer from a transmission risk problem because the noise-like shares will raise the suspicion of attackers and the attackers might intercept the transmission. Previous research has involved in hiding shared content in halftone shares to reduce these risks, but this method exacerbates the pixel expansion problem and visual quality degradation problem for recovered images. In this paper, a binocular VCS (BVCS), called the (2,n)-BVCS, and an encryption algorithm are proposed to hide the shared pixels in the single image random dot stereograms (SIRDSs). Because the SIRDSs have the same 2D appearance as the conventional shares of a VCS, this paper tries to use SIRDSs as cover images of the shares of VCSs to reduce the transmission risk of the shares. The encryption algorithm alters the random dots in the SIRDSs according to the construction rule of the (2,n)-BVCS to produce nonpixel-expansion shares of the BVCS. Altering the dots in a SIRDS will degrade the visual quality of the reconstructed 3D objects. Hence, we propose an optimization model that is based on the visual quality requirement of SIRDSs to develop construction rules for a (2,n)-BVCS that maximize the contrast of the recovered image in the BVCS. PMID- 25122572 TI - VSI: a visual saliency-induced index for perceptual image quality assessment. AB - Perceptual image quality assessment (IQA) aims to use computational models to measure the image quality in consistent with subjective evaluations. Visual saliency (VS) has been widely studied by psychologists, neurobiologists, and computer scientists during the last decade to investigate, which areas of an image will attract the most attention of the human visual system. Intuitively, VS is closely related to IQA in that suprathreshold distortions can largely affect VS maps of images. With this consideration, we propose a simple but very effective full reference IQA method using VS. In our proposed IQA model, the role of VS is twofold. First, VS is used as a feature when computing the local quality map of the distorted image. Second, when pooling the quality score, VS is employed as a weighting function to reflect the importance of a local region. The proposed IQA index is called visual saliency-based index (VSI). Several prominent computational VS models have been investigated in the context of IQA and the best one is chosen for VSI. Extensive experiments performed on four large-scale benchmark databases demonstrate that the proposed IQA index VSI works better in terms of the prediction accuracy than all state-of-the-art IQA indices we can find while maintaining a moderate computational complexity. The MATLAB source code of VSI and the evaluation results are publicly available online at http://sse.tongji.edu.cn/linzhang/IQA/VSI/VSI.htm. PMID- 25122573 TI - Patchwise joint sparse tracking with occlusion detection. AB - This paper presents a robust tracking approach to handle challenges such as occlusion and appearance change. Here, the target is partitioned into a number of patches. Then, the appearance of each patch is modeled using a dictionary composed of corresponding target patches in previous frames. In each frame, the target is found among a set of candidates generated by a particle filter, via a likelihood measure that is shown to be proportional to the sum of patch reconstruction errors of each candidate. Since the target's appearance often changes slowly in a video sequence, it is assumed that the target in the current frame and the best candidates of a small number of previous frames, belong to a common subspace. This is imposed using joint sparse representation to enforce the target and previous best candidates to have a common sparsity pattern. Moreover, an occlusion detection scheme is proposed that uses patch-reconstruction errors and a prior probability of occlusion, extracted from an adaptive Markov chain, to calculate the probability of occlusion per patch. In each frame, occluded patches are excluded when updating the dictionary. Extensive experimental results on several challenging sequences shows that the proposed method outperforms state-of the-art trackers. PMID- 25122574 TI - A universal variational framework for sparsity-based image inpainting. AB - In this paper, we extend an existing universal variational framework for image inpainting with new numerical algorithms. Given certain regularization operator Phi and denoting u the latent image, the basic model is to minimize the l(p), (p=0,1) norm of Phiu preserving the pixel values outside the inpainting region. Utilizing the operator splitting technique, the original problem can be approximated by a new problem with extra variable. With the alternating minimization method, the new problem can be decomposed as two subproblems with exact solutions. There are many choices for Phi in our approach such as gradient operator, wavelet transform, framelet transform, or other tight frames. Moreover, with slight modification, we can decouple our framework into two relatively independent parts: 1) denoising and 2) linear combination. Therefore, we can take any denoising method, including BM3D filter in the denoising step. The numerical experiments on various image inpainting tasks, such as scratch and text removal, randomly missing pixel filling, and block completion, clearly demonstrate the super performance of the proposed methods. Furthermore, the theoretical convergence of the proposed algorithms is proved. PMID- 25122575 TI - Design, synthesis, and characterization of 1,3,5-tri(1H-benzo[d]imidazol-2 yl)benzene-based fluorescent supramolecular columnar liquid crystals with a broad mesomorphic range. AB - A new kind of supramolecular columnar liquid crystal T-A with a broad mesomorphic range (up to 164.9 degrees C), good thermal stability, and strong fluorescence is designed and formed by the H-bonding between 1,3,5-tri(1H-benzo[d]imidazol-2 yl)benzene (T) and serial gallic acid derivatives (A). Two components are easily available because of simple routes, common reactions, high yields, commercial starting materials, and inexpensive catalysts. The introduction of the 1,2,3 triazole structure into component A makes the textures different and is slightly disadvantageous for the T-A complexes. PMID- 25122576 TI - The changing relationship between bacterial STIs and HIV prevalence in South Africa - an ecological study. AB - Prevalence estimates of various bacterial sexually transmitted infections in South Africa have declined considerably since the mid-1990s. Syphilis among pregnant women, for example, declined from 10.8% in 1998 to 2.8% in 2001. We used Pearson's correlation coefficients to estimate the association between the prevalence of syphilis/male urethral discharge/male genital ulcers and the peak HIV prevalence at a district and provincial level in the early and late phases of the HIV epidemic in South Africa. Prevalence estimates of syphilis, male urethral discharge and male genital ulcers during the period preceding the peak HIV prevalence were all positively correlated with the peak HIV prevalence at a provincial level (Pearson's correlation coefficient [r] = 0.83, p = 0.006; r = 0.66, p = 0.052; r = 0.79, 0.011, respectively). These relationships all switched to a negative association later in the HIV epidemic at a provincial level (r = 0.53, p = 0.14; r = -0.73, p = 0.130; r = -0.54, p = 0.027, respectively). AIDS mortality may have played an important role in the decline of bacterial sexually transmitted infections such as syphilis in this region. Consequently, the relatively recent scale-up of antiretroviral therapy may result in a resurgence of syphilis and other sexually transmitted infections as observed in high-income countries. PMID- 25122577 TI - A case of relapsed visceral Kaposi's sarcoma with bilateral chylothoraces successfully treated with paclitaxel. AB - Chylothorax is a rare complication of visceral Kaposi's sarcoma. We report a case with bilateral chylothoraces secondary to relapsed visceral Kaposi's sarcoma who was successfully treated with paclitaxel chemotherapy. PMID- 25122578 TI - Antiretroviral treatment failure predicts mortality in rural Tanzania. AB - Virological monitoring of HIV-infected patients on antiretroviral treatment (ART) is rarely available in resource-limited settings and many patients experience unrecognized virological failure. We studied the long-term consequences of virological failure in rural Tanzania. Previously, virological efficacy was measured in a cohort treated with ART. In the present study, patients with virological failure (VF; HIV-RNA >400 copies/ml) were followed up and compared to those with virological response (VR; HIV-RNA <400 copies/ml) with regard to mortality, CD4 change and subsequent virological outcome. Fifty-six patients with VF had a median CD4 count of 358 cells/ul (interquartile range [IQR] 223-635) and a median HIV-RNA of 13,573 copies/ml (IQR 2326-129,736). Median CD4 count for those with VR was 499 cells/ul (IQR 290-636). During a median follow-up time of 39 months (IQR 18-42), 8 of 56 patients (14.3%) with VF died, compared to 1 of 63 patients (1.6%) with VR (p = 0.009). All registered deaths were HIV-related. Of 55 patients with subsequent HIV-RNA measurements, only 12 of 30 (40%) patients with VF achieved virological suppression, compared to 20 of 25 (80%) patients with VR (p = 0.003). Virological failure predicted death and subsequent virological failure in patients on ART in a resource-limited setting. PMID- 25122579 TI - Measuring patient satisfaction: three years' data and experience of using a validated patient questionnaire. AB - A validated patient satisfaction questionnaire for use in sexual health clinics was run throughout the southwest region (the UK) three times over three years (13 clinics in January 2012 and 12/13 clinics in January 2013 and the same 12 clinics again in January 2014). The questionnaire covered aspects of pre-appointment, performance of health care professionals, facilities, privacy, respectful communication, information on leaving and overall experience. Data from 1750 questionnaires are presented with means and 95% confidence intervals. Patients under the age of 25 were less likely to rate care as excellent and/or very good (P = 0.001) compared with those above the age of 25. There was no difference in satisfaction levels according to gender or sexual orientation. Time in clinic was strongly associated with satisfaction levels - those in clinic for over 90 min expressed less satisfaction (P = 0.0005). We hope that other clinics may find it useful to use the validated questionnaire to look at their own performance and compare it against the southwest data. The main value is to identify areas where changes to service delivery could translate into improved practice and improved satisfaction, particularly where performance is identified as less than the 95% confidence intervals. PMID- 25122580 TI - Does dropping day 5 PEP follow-up affect outcomes? An audit of HIV post-exposure prophylaxis at a central London sexual health clinic. AB - UK post-exposure prophylaxis (PEP) guidelines were updated by the British Association for Sexual Health and HIV (BASHH) in 2011. In 2013, we changed policy to omit day 5 PEP follow-up at 56 Dean Street as it was felt clinically unnecessary. This audit compares our performance against BASHH standards for PEP attenders during June 2012 and June 2013. We identified 162 PEP prescriptions; PEP assessment and appropriate sexually transmitted infection testing was done well. PEP completion rates and post-PEP HIV testing were lower than BASHH standards. Following omission of day 5 review, documentation that results have been checked was poor; however, attendance at follow-up was not adversely affected. PMID- 25122582 TI - Covalent linking of quantum dots to polymer for inorganic-inorganic luminescence films via layer-by-layer assembly with clay. AB - Herein, positively charged QDs were initially prepared by covalently linking to poly(allylamine hydrochloride) (PAH). The resulting PAH-modified QDs in conjunction with MMT nanosheets were utilized to fabricate QDs/MMT UTFs via LBL assembly. Strong photoluminescence, temperature responsiveness, long-term stability and high uniformity make these films potential candidates for a wide range of applications. PMID- 25122583 TI - Health Characteristics by Geographic Region, large Metropolitan Areas, and Other Places of Residence, United States - 1969-70. AB - The estimates for selected health characteristics presented in this report are based on Health Interview Survey data collected during 1969-70. The health characteristics discussed include activity limitation due to chronic disease, disability days, incidence of acute conditions and persons injured, hospitalization, and physician and dental visits. The information is shown by the four geographic regions, metropolitan areas, and farm and nonfarm places of residence outside the metropolitan areas. Another breakdown of the data shows estimates by residence inside or outside the metropolitan area. An earlier report (Vital and Health Statistics Series 10, No. 36) contained similar information for the period July 1963-June 1965. PMID- 25122581 TI - Social inequalities in early childhood health and development: a European-wide systematic review. AB - The evidence examining the relationship between specific social factors and early childhood health and developmental outcomes has never been systematically collated or synthesized. This review aims to identify the key social factors operating at the household, neighborhood, and country levels that drive inequalities in child health and development. Medline and CHICOS (a European child-cohort inventory) were systematically searched to identify all European studies published within the past 10 y. 13,270 Medline articles and 77 European child cohorts were searched, identifying 201 studies from 32 European countries. Neighborhood deprivation, lower parental income/wealth, educational attainment, and occupational social class, higher parental job strain, parental unemployment, lack of housing tenure, and household material deprivation were identified as the key social factors associated with a wide range of adverse child health and developmental outcomes. Similar association trends were observed across most European countries, with only minor country-level differences. Multiple adverse social factors operating at both the household and neighborhood levels are independently associated with a range of adverse health and developmental outcomes throughout early childhood. The social gradient in health and developmental outcomes observed throughout the remaining life course may be partly explained by gradients initiated in early childhood. PMID- 25122585 TI - Re: "Estimated rate of reactivation of latent tuberculosis infection in the United States, overall and by population subgroup". PMID- 25122584 TI - Validity of an ecometric neighborhood physical disorder measure constructed by virtual street audit. AB - Neighborhood physical disorder is thought to affect mental and physical health, but it has been difficult to measure objectively and reliably across large geographical areas or multiple locales. Virtual street audits are a novel method for assessing neighborhood characteristics. We evaluated the ecometric properties of a neighborhood physical disorder measure constructed from virtual street audit data. Eleven trained auditors assessed 9 previously validated items developed to capture physical disorder (e.g., litter, graffiti, and abandoned buildings) on 1,826 block faces using Google Street View imagery (Google, Inc., Mountain View, California) dating from 2007-2011 in 4 US cities (San Jose, California; Detroit, Michigan; New York, New York; and Philadelphia, Pennsylvania). We constructed a 2 parameter item response theory scale to estimate latent levels of disorder on each block face and defined a function using kriging to estimate physical disorder levels, with confidence estimates, for any point in each city. The internal consistency reliability of the resulting scale was 0.93. The final measure of disorder was positively correlated with US Census data on unemployment and housing vacancy and negatively correlated with data on owner-occupied housing. These results suggest that neighborhood physical disorder can be measured reliably and validly using virtual audits, facilitating research on possible associations between physical disorder and health. PMID- 25122586 TI - High-frequency transcutaneous electrical nerve stimulation alleviates spasticity after spinal contusion by inhibiting activated microglia in rats. AB - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) can be used as a physical therapy for spasticity, but the effects of TENS on spasticity and its underlying mechanisms remain unclear. OBJECTIVE: The purpose of this study was to test the effects of TENS on spasticity and the role of activated microglia as underlying mechanisms of TENS treatment for spasticity in rats with a 50-mm contusive spinal cord injury (SCI). METHODS: A spinal contusion was made at the T12 spinal segment in adult male Sprague-Dawley rats using the NYU impactor. Behavioral tests for motor function were conducted before and after SCI and before and after TENS application. To assess spasticity, the modified Ashworth scale (MAS) was used before and after SCI, high-frequency (HF)/low-frequency (LF) TENS application at 3 different intensities (motor threshold [MT], 50% and 90% MT) or minocycline administration. Immunohistochemistry for microglia was performed at the lumbar spinal segments. RESULTS: Motor recovery reached a plateau approximately 28 days after SCI. Spasticity was well developed and was sustained above the MAS grade of 3, beginning at 28 days after SCI. HF-TENS at 90% MT significantly alleviated spasticity. Motor function did not show any significant changes with LF- or HF-TENS treatment. HF-TENS significantly reduced the proportion of activated microglia observed after SCI. Minocycline, the microglia inhibitor, also significantly alleviated spasticity with the reduction of activated microglia expression. CONCLUSIONS: These results suggest that HF TENS at 90% MT alleviates spasticity in rats with SCI by inhibiting activated microglia. PMID- 25122588 TI - An investigation of heat transfer between a microcantilever and a substrate for improved thermal topography imaging. AB - This paper reports the numerical and experimental investigation of heat transfer from a heated microcantilever to a substrate and uses the resulting insights to improve thermal topography imaging. The cantilever sensitivity, defined as change in thermal signal due to changes in the topography height, is relatively constant for feature heights in the range 100-350 nm. Since the cantilever-substrate heat transfer is governed by thermal conduction through the air, the cantilever sensitivity is nearly constant across substrates of varying thermal conductivity. Surface features with lateral size larger than 2.5 MUm can induce artifacts in the cantilever signal resulting in measurement errors as large as 28%. These artifacts arise from thermal conduction from the cantilever in the lateral direction, parallel to the surface. We show how these artifacts can be removed by accounting for this lateral conduction and removing it from the thermal signal. This technique reduces the measurement error by as much as 26%, can be applied to arbitrary substrate topographies, and can be scaled to arrays of heated cantilevers. These results could lead to improvements in nanometer-scale thermal measurements including scanning thermal microscopy and tip-based nanofabrication. PMID- 25122587 TI - Varied overground walking training versus body-weight-supported treadmill training in adults within 1 year of stroke: a randomized controlled trial. AB - BACKGROUND: Although task-related walking training has been recommended after stroke, the theoretical basis, content, and impact of interventions vary across the literature. There is a need for a comparison of different approaches to task related walking training after stroke. OBJECTIVE: To compare the impact of a motor-learning-science-based overground walking training program with body-weight supported treadmill training (BWSTT) in ambulatory, community-dwelling adults within 1 year of stroke onset. METHODS: In this rater-blinded, 1:1 parallel, randomized controlled trial, participants were stratified by baseline gait speed. Participants assigned to the Motor Learning Walking Program (MLWP) practiced various overground walking tasks under the supervision of 1 physiotherapist. Cognitive effort was encouraged through random practice and limited provision of feedback and guidance. The BWSTT program emphasized repetition of the normal gait cycle while supported on a treadmill and assisted by 1 to 3 therapy staff. The primary outcome was comfortable gait speed at postintervention assessment (T2). RESULTS: In total, 71 individuals (mean age = 67.3; standard deviation = 11.6 years) with stroke (mean onset = 20.9 [14.1] weeks) were randomized (MLWP, n = 35; BWSTT, n = 36). There was no significant between-group difference in gait speed at T2 (0.002 m/s; 95% confidence interval [CI] = -0.11, 0.12; P > .05). The MLWP group improved by 0.14 m/s (95% CI = 0.09, 0.19), and the BWSTT group improved by 0.14 m/s (95% CI = 0.08, 0.20). CONCLUSIONS: In this sample of community-dwelling adults within 1 year of stroke, a 15-session program of varied overground walking-focused training was not superior to a BWSTT program of equal frequency, duration, and in-session step activity. PMID- 25122589 TI - In situ assembly of well-dispersed Ni nanoparticles on silica nanotubes and excellent catalytic activity in 4-nitrophenol reduction. AB - The easy aggregation nature of ferromagnetic nanoparticles (NPs) prepared by conventional routes usually leads to a large particle size and low loading, which greatly limits their applications to the reduction of 4-nitrophenol (4-NP). Herein, we developed a novel in situ thermal decomposition and reduction strategy to prepare Ni nanoparticles/silica nanotubes (Ni/SNTs), which can markedly prevent the aggregation and growth of Ni NPs, resulting in an ultra-small particle size (about 6 nm), good dispersion and especially high loading of Ni NPs. It was found that Ni/SNTs, which have a high specific surface area (416 m(2) g(-1)), exhibit ultra-high catalytic activity in the 4-NP reduction (complete reduction of 4-NP within only 60 s at room temperature), which is superior to most noble metal (Au, Pt, and Pd) supported catalysts. Ni/SNTs still showed high activity even after re-use for several cycles, suggesting good stability. In particular, the magnetic property of Ni/SNTs makes it easy to recycle for reuse. PMID- 25122590 TI - Preorganized bis-thioureas as powerful anion carriers: chloride transport by single molecules in large unilamellar vesicles. AB - Transmembrane anion carriers (anionophores) have potential in biological research and medicine, provided high activities can be obtained. There is particular interest in treating cystic fibrosis (CF), a genetic illness caused by deficient anion transport. Previous work has found that anionophore designs featuring axial ureas on steroid and trans-decalin scaffolds can be especially effective. Here we show that replacement of ureas by thioureas yields substantial further enhancements. Six new bis-thioureas have been prepared and tested for Cl(-)/NO3( ) exchange in 1-palmitoyl-2-oleoylphosphatidylcholine/cholesterol large unilamellar vesicles (LUVs). The bis-thioureas are typically >10 times more effective than the corresponding ureas and are sufficiently active that transport by molecules acting singly in LUVs is readily detected. The highest activity is shown by decalin 9, which features N-(3,5-bis(trifluoromethyl)phenyl)thioureido and octyl ester substituents. A single molecule of transporter 9 in a 200 nm vesicle promotes Cl(-)/NO3(-) exchange with a half-life of 45 s and an absolute rate of 850 chloride anions per second. Weight-for-weight, this carrier is only slightly less effective than CFTR, the natural anion channel associated with CF. PMID- 25122592 TI - Biomimetic and bioinspired materials for applications in biophotonics. PMID- 25122591 TI - MR compatibility aspects of a silicon photomultiplier-based PET/RF insert with integrated digitisation. AB - The combination of Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) into a single device is being considered a promising tool for molecular imaging as it combines the high sensitivity of PET with the functional and anatomical images of MRI. For highest performance, a scalable, MR compatible detector architecture with a small form factor is needed, targeting at excellent PET signal-to-noise ratios and time-of-flight information. Therefore it is desirable to use silicon photo multipliers and to digitize their signals directly in the detector modules inside the MRI bore. A preclinical PET/RF insert for clinical MRI scanner was built to demonstrate a new architecture and to study the interactions between the two modalities.The disturbance of the MRI's static magnetic field stays below 2 ppm peak-to-peak within a diameter of 56 mm (90 mm using standard automatic volume shimming). MRI SNR is decreased by 14%, RF artefacts (dotted lines) are only visible in sequences with very low SNR. Ghosting artefacts are visible to the eye in about 26% of the EPI images, severe ghosting only in 7.6%. Eddy-current related heating effects during long EPI sequences are noticeable but with low influence of 2% on the coincidences count rate. The time resolution of 2.5 ns, the energy resolution of 29.7% and the volumetric spatial resolution of 1.8 mm(3) in the PET isocentre stay unaffected during MRI operation. Phantom studies show no signs of other artefacts or distortion in both modalities. A living rat was simultaneously imaged after the injection with (18)F-Fluorodeoxyglucose (FDG) proving the in vivo capabilities of the system. PMID- 25122593 TI - Design and control of a dual unidirectional brake hybrid actuation system for haptic devices. AB - Hybrid actuators combining brakes and motors have emerged as an efficient solution to achieve high performance in haptic devices. In this paper, an actuation approach using two unidirectional brakes and a DC motor is proposed. The brakes are coupled to overrunning clutches and can apply a torque in only one rotational direction. The associated control laws, that are independent of the virtual environment model, calculate the control gains in real time in order limit the energy and the stiffness delivered by the motor to ensure stability. The reference torque is respected using the combination of the motor and the brake. Finally, an user experiment has been performed to evaluate the influence of passive and active torque differences in the perception of elasticity. The proposed actuator has a torque range of 0.03 Nm to 5.5 Nm with a 17.75 kNm (-2) torque density. PMID- 25122594 TI - Velocity estimation algorithms for audio-haptic simulations involving stick-slip. AB - With real-time models of friction that take velocity as input, accuracy depends in great part on adequately estimating velocity from position measurements. This process can be sensitive to noise, especially at high sampling rates. In audio haptic acoustic simulations, often characterized by friction-induced, relaxation type stick-slip oscillations, this gives a gritty, dry haptic feel and a raspy, unnatural sound. Numerous techniques have been proposed, but each depend on tuning parameters so that they may offer a good trade-off between delay and noise rejection. In an effort to compare fairly, each of thirteen methods considered in the present study was automatically optimized and evaluated; finally a subset of these were compared subjectively. Results suggest that no one method is ideal for all gain levels, though the best general performance was found by using a sliding mode differentiator as input to a Kalman integrator. An additional conclusion is that estimators do not approach the quality available in physical velocity transduction, and therefore such sensors should be considered in haptic device design. PMID- 25122595 TI - Pilot study of a new rehabilitation tool: improved unilateral short-term adaptation of the human angular vestibulo-ocular reflex. AB - HYPOTHESIS: Unilateral vestibulo-ocular reflex (VOR) short-term adaptation training causes some increase toward the nonadapting side (~30% of increase on adapting side). We conducted a pilot study to determine if the increase could be reduced by providing a visual stimulus during rotations to the nonadapting side. BACKGROUND: Unilateral vestibular short-term adaptation is a technique that could increase the ipsilesional VOR response of vestibular patients with unilateral hypofunction. However, this technique results in the VOR response increasing for rotations toward the nonadapting (normal) side, which is undesirable because the VOR will be overcompensatory (causing nonstable vision) during head rotations toward the normal side. METHODS: We built a portable helmet device that sensed horizontal angular head velocity to generate a visual target that required a preset VOR gain (eye velocity/head velocity) for optimal image stabilization that could be set differently for leftward and rightward head rotations. We tested 10 subjects (six controls and four patients with vestibular hypofunction). We measured the active and passive VOR gain during high-peak-acceleration, unilateral, transient head rotations (head impulses) before and after unilateral VOR adaptation training. RESULTS: In control subjects, for rotations toward the adapting side (target gain = 1.5), the VOR gain increased because of training by 26.1% +/- 23.4% during active head impulses and by 14.6% +/- 13.0% during passive head impulses. In contrast, for rotations toward the nonadapting side, there were no statistically significant increases. CONCLUSION: A visual stimulus driving the VOR gain to unity toward the nonadapting side aids unilateral adaptation more so than no visual stimulus. PMID- 25122596 TI - Dizziness is more prevalent than autophony among patients who have undergone repair of superior canal dehiscence. AB - OBJECTIVE: Studies have reported high early success rates in rectifying dizziness and autophony after primary repair of superior canal dehiscence (SCD). We sought to identify the prevalence of dizziness and autophony at later time points in patients who had undergone SCD repair. We also assessed any problems with hearing in this population, along with prevalence of headaches and decreases in overall quality of life. STUDY QUALITY DESIGN: Identification of patients via retrospective chart review, followed by administration of multiple validated surveys. SETTING: Tertiary, hospital-based neurotology practice. PATIENTS: All 62 patients who had undergone primary SCD repair at Massachusetts Eye and Ear Infirmary with follow-up time of at least 3 months were contacted, with 38 responses from 22 women and 16 men. The average follow-up was 34 months (range, 3 155 mo). INTERVENTIONS: Patient surveys. MAIN OUTCOME MEASURES: Dizziness Handicap Inventory and Autophony Index. SECONDARY OUTCOME MEASURES: Hearing Handicap Survey, MIDAS headache survey, and Short Form-36 Quality of Life Survey. RESULTS: Twenty patients reported low DHI scores, whereas 18 patients reported elevated DHI scores corresponding to moderate-to-severe dizziness. Autophony was less prevalent, as 3 patients experienced autophony in the operated ear, whereas 3 patients experienced "unmasking" of autophony in the contralateral ear. HHI scores were not significantly different between the low DHI and high DHI group. There were significantly more female subjects in the high DHI group, which was also characterized by significantly more severe MIDAS grades and significantly worse SF-36 scores. CONCLUSION: Dizziness is more prevalent than autophony among patients who have undergone SCD repair, although the majority of these patients are satisfied with their decision to undergo surgery. Female sex and migraine headaches are associated with dizziness in this patient population. Further work is necessary to determine causal relationships among these associations. PMID- 25122597 TI - Intratympanic steroid injection for Bell's palsy: preliminary randomized controlled study. AB - OBJECTIVE: To investigate adjuvant effect and safety of intratympanic steroid for the treatment of Bell's palsy. STUDY DESIGN: Prospective, investigator blinded, randomized study. SETTING: Tertiary referral center. PATIENTS: Patients who received treatment for Bell's palsy from December 2007 to March 2011 were randomly divided into two groups. The control group (n = 17) was treated with systemic steroid plus antiviral agent, and intratympanic steroid injection group (IT group, n = 14) received intratympanic steroid injection combined with medications. Facial functions were evaluated on a regular basis up to 6 months. INTERVENTION: Intratympanic steroid injection. MAIN OUTCOME MEASURES: Facial nerve functions of initial presentation and follow-up were evaluated with House Brackmann (H-B) system. Primary outcome was complete recovery rate of 6 months. Secondary outcomes included improvement of H-B grade within 3 weeks, time of first improvement in facial function, and cumulative recovery rate. In addition, subgroup analysis of H-B grade over than IV was performed. RESULTS: Complete recovery rate was not different between groups. Time of first improvement was shorter in IT group (p = 0.043). And IT group had a better cumulative recovery rate (p = 0.041) and showed the significant improvement in H-B grade within 3 weeks compared with control group (p = 0.045). In severe facial palsy, complete recovery rate of IT group and control group were 80% and 50% (p = 0.16), and IT groups showed the significant facial improvement within 3 weeks (p = 0.025). And there were no major adverse effects of intratympanic injection. CONCLUSION: Intratympanic steroid injection might be a safe and useful adjuvant treatment modality for Bell's palsy. PMID- 25122598 TI - Long-term results of 185 consecutive osseointegrated hearing device implantations: a comparison among children, adults, and elderly. AB - OBJECTIVE: To determine the occurrence and type of perioperative and postoperative complications in patients implanted with an osseointegrated hearing device (OHD) (also known as BAHA/BAHS) and compare results in children, adults, and elderly and for different surgical techniques. STUDY DESIGN: Retrospective case file review. SETTING: Tertiary referral center. PATIENTS: Patients implanted with an OHD between 2004 and 2012, with more than 6 months of follow-up. INTERVENTION: OHD implantation. MAIN OUTCOME MEASURES: Implant loss, adverse skin reactions (Holgers' score, >=2), skin overgrowth, and discomfort resulting in abutment and/or implant removal. RESULTS: One hundred eighty-five implantations in 176 patients were reviewed. Overall, 3.8% of the implants were lost spontaneously after a mean of 2.5 years. Implant loss in children was 18% versus 2.5% in adults and 3.8% in elderly. Adverse skin reactions occurred in 14% of observations overall; in 10% in children compared with 16% in adults and 9% in elderly. Partial or total skin overgrowth was seen in 4% and 6% of the observations in children and adults, respectively, whereas none of the elderly experienced this problem. The abutment was removed because of discomfort and/or no benefit in 10% overall, in 13% of adults, and in 6% of the elderly; none of the children opted for removal. Linear incision technique showed fewest complications. CONCLUSION: OHD implantation is a procedure with few major complications. Adverse skin reaction is the most common complication. Children lose the implant more frequently than adults. Elderly patients have less adverse skin reactions/skin overgrowth. Discomfort leading to abutment removal is a concern especially among adults. PMID- 25122599 TI - Calvarium thinning in patients with spontaneous cerebrospinal fluid leak. AB - OBJECTIVE: To determine the thickness of the calvarium in patients with spontaneous cerebrospinal fluid (CSF) leaks. STUDY DESIGN: Case control study. SETTING: University of Iowa Hospitals and Clinics. PATIENTS: Those with a confirmed spontaneous CSF leak compared to non-obese (body mass index, BMI < 30) and obese (BMI >= 30) cochlear implant (CI) control groups. All patients had to have temporal bone CT scans that fit specified criteria. INTERVENTION: Bilateral volumetric analysis of the squamous temporal bone and the zygoma in all patients. Assessment of patient age, sex, BMI, and medical comorbidities. MAIN OUTCOME MEASURE: Assessment of the average thickness of the squamous temporal bone and zygoma compared to control groups. RESULTS: The average BMI of patients with spontaneous CSF leaks was significantly higher than non-obese CI controls (43.73 +/- 9.19 vs. 24.60 +/- 3.10; P < 0.0001). The calvarium in patients with spontaneous CSF leaks was 23% thinner than both non-obese CI controls (3.29 +/- 0.68 vs. 4.25 +/- 0.58; P < 0.0001) and obese CI controls (3.29 +/- 0.68 vs. 4.27 +/- 0.68; P < 0.0001). In addition, the skull thickness of obese CI patients (body mass index, BMI = 37.34 +/- 6.1) was not significantly different from non obese CI controls (4.27 +/- 0.68 vs. 4.25 +/- 0.58; P = 0.92). The extracranial zygoma was not significantly different among the three groups (ANOVA = 0.9). In our study groups, 5.8% of both CI control groups had the diagnosis of obstructive sleep apnea (OSA), whereas 46.2% of the spontaneous CSF leak patients presented with the diagnosis of OSA. CONCLUSION: Patients with spontaneous CSF leak are more likely to be obese, have the diagnosis of OSA, and show thinning of their entire calvarium that is independent of BMI. These data suggest an additional obesity-associated intracranial process contributes to skull thinning. PMID- 25122601 TI - Influence of cochlear implant insertion depth on performance: a prospective randomized trial. AB - OBJECTIVE: The purpose of the present study was to assess the influence of electrode insertion length on cochlear implant (CI) performance. STUDY DESIGN: Prospective randomized allocation of CI patients to receive either a standard (26.4 mm)- or medium (20.9 mm)-length electrode array. The processing strategy and electrode insertion number were held constant. The postoperative testing audiologist was blinded to the map details and array. SETTING: Tertiary referral center. PATIENTS: Thirteen adult CI candidates randomized to receive the standard (n = 7) or medium-length (n = 6) electrode array. INTERVENTION(S): Unilateral CI using standard- or medium-length array from the same implant system. MAIN OUTCOME MEASURES(S): Speech perception was assessed with HINT sentences in quiet and steady-state noise (SNR, +10) and CNC words in quiet at defined intervals. Quality of life was assessed using the Hearing Device Satisfaction Survey and the Abbreviated Profile of Hearing Aid Benefit (APHAB). Music perception was assessed using the Musical Sounds In Cochlear implants (MuSIC) test. Postoperative electrode insertion angle was assessed using reconstructed computed tomographic images. RESULTS: Interim analysis necessitated discontinuation of subject enrollment by the institutional review board. There was a trend (p = 0.07) for improved speech perception performance among standard array patients. This difference was significant when the standard array group was increased retrospectively. Quality of life and music perception differences were not apparent between groups. CONCLUSION: Longer electrode insertions (and greater insertion angles) appear to offer better speech perception performance in the early postactivation period when using the same implant system. PMID- 25122600 TI - Intracochlear inflammatory response to cochlear implant electrodes in humans. AB - HYPOTHESIS: This study evaluates the types and degrees of tissue response adjacent to the electrode of multichannel cochlear implants. BACKGROUND: Cochlear implant electrodes have been classified as biocompatible prostheses. Nevertheless, in some reports, electrode extrusion, chronic inflammation, and even soft failure of the implant system have been attributed to a tissue response to the electrode. METHODS: All celloidin-embedded temporal bones with multichannel cochlear implants from the temporal bone collection of the Massachusetts Eye and Ear Infirmary were included in the study. A total of 28 temporal bones from 21 subjects were identified and processed for histology. The severity of cellular response including eosinophil and lymphocytic infiltration, giant cell reaction, new bone formation, and fibrosis were scored on a scale from 0 to 3 at three 1-mm segments along the electrode: first 1 mm at the cochleostomy, last 1 mm from the tip of the electrode, and midway between these proximal and distal segments. The values were compared using the Wilcoxon test. RESULTS: A granulomatous reaction to the electrode was observed in 27 (96.4%) temporal bones. Eosinophil infiltration was observed in 7 (25%) temporal bones, suggesting an allergic reaction. The Inflammatory response to the electrode was significantly greater at the basal turn of cochlea close to the cochleostomy (p < 0.05) than distal to it. CONCLUSION: An inflammatory response is common after cochlear implantation, and it is more robust at the cochleostomy than distal to it, suggesting the role of trauma of insertion as a contributing factor. PMID- 25122602 TI - Radiologic classification of superior canal dehiscence: implications for surgical repair. AB - OBJECTIVE: Surgical access to repair a superior canal dehiscence (SCD) is influenced by the location of the bony defect and its relationship to surrounding tegmen topography as seen on computed tomography. There are currently no agreed upon methods of characterizing these radiologic findings. We propose a formal radiologic classification system of SCD based on dehiscence location and adjacent tegmen topography. STUDY DESIGN: Retrospective case review SETTING: Tertiary, neurotology referral center PATIENTS: We identified 298 patients with superior canal dehiscence on CT from February 2001 to October 2013. Of these, 251 had symptomatic superior canal dehiscence syndrome and were included in the study. INTERVENTION: Patients underwent high-resolution temporal bone CT scans with creation of axial, coronal, Poschl, and Stenver reformatted images to examine the superior semicircular canal. Two residents-in-training and a head and neck radiologist independently read the scans. MAIN OUTCOME MEASURES: CT scans were assessed for (1) superior canal dehiscence or "near" dehiscence, (2) defect location relative to the skull base, (3) surrounding tegmen defects, (4) geniculate ganglion dehiscence, (5) superior petrosal sinus-associated dehiscence (SPS), (6) low-lying tegmen, and (7) the distance between the outer table of the temporal bone and the arcuate eminence. PMID- 25122603 TI - A Neurodynamic Optimization Method for Recovery of Compressive Sensed Signals With Globally Converged Solution Approximating to l0 Minimization. AB - Finding the optimal solution to the constrained l0 -norm minimization problems in the recovery of compressive sensed signals is an NP-hard problem and it usually requires intractable combinatorial searching operations for getting the global optimal solution, unless using other objective functions (e.g., the l1 norm or lp norm) for approximate solutions or using greedy search methods for locally optimal solutions (e.g., the orthogonal matching pursuit type algorithms). In this paper, a neurodynamic optimization method is proposed to solve the l0 -norm minimization problems for obtaining the global optimum using a recurrent neural network (RNN) model. For the RNN model, a group of modified Gaussian functions are constructed and their sum is taken as the objective function for approximating the l0 norm and for optimization. The constructed objective function sets up a convexity condition under which the neurodynamic system is guaranteed to obtain the globally convergent optimal solution. An adaptive adjustment scheme is developed for improving the performance of the optimization algorithm further. Extensive experiments are conducted to test the proposed approach in this paper and the output results validate the effectiveness of the new method. PMID- 25122604 TI - Identifying Similar Cases in Document Networks Using Cross-Reference Structures. AB - Our objective was to explore the creation of document networks based on different thresholds of shared information and different clustering algorithms on those networks to identify document clusters describing similar clinical cases. We created networks from vaccine adverse event report sets using seven approaches for linking reports. We then applied three clustering algorithms [visualization of similarities (VOS), Louvain, k-means] to these networks and evaluated their ability to identify known clusters. The report sets included one simulated set and three sets from the Vaccine Adverse Event Reporting System; each was split into training and testing subsets. Training subsets were used to estimate parameter values for the clustering algorithms and testing subsets to evaluate clusters. We created the networks by linking reports based on shared information in the form either of individual Medical Dictionary for Regulatory Activities Preferred Terms (PTs) or of dyads, triplets, quadruplets, quintuplets, and sextuplets of PTs; we created another network by weighting the single PT network connections by Lin's information theoretic approach to similarity. We then repeated this entire process using networks based on text mining output rather than structured data. We evaluated report clustering using recall, precision, and f-measure. The VOS algorithm outperformed Louvain and k-means in general. The best weighting scheme appeared to be related to the complexity of the known cluster. For example, singleton weighting performed best for an intussusception cluster driven by a single PT. We observed marginal differences between the code- and textual-based clustering. In conclusion, our approach supported identification of similar nodes in a document network. PMID- 25122605 TI - Accurate segmentation of partially overlapping cervical cells based on dynamic sparse contour searching and GVF snake model. AB - Overlapping cells segmentation is one of the challenging topics in medical image processing. In this paper, we propose to approximately represent the cell contour as a set of sparse contour points, which can be further partitioned into two parts: the strong contour points and the weak contour points. We consider the cell contour extraction as a contour points locating problem and propose an effective and robust framework for segmentation of partially overlapping cells in cervical smear images. First, the cell nucleus and the background are extracted by a morphological filtering-based K-means clustering algorithm. Second, a gradient decomposition-based edge enhancement method is developed for enhancing the true edges belonging to the center cell. Then, a dynamic sparse contour searching algorithm is proposed to gradually locate the weak contour points in the cell overlapping regions based on the strong contour points. This algorithm involves the least squares estimation and a dynamic searching principle, and is thus effective to cope with the cell overlapping problem. Using the located contour points, the Gradient Vector Flow Snake model is finally employed to extract the accurate cell contour. Experiments have been performed on two cervical smear image datasets containing both single cells and partially overlapping cells. The high accuracy of the cell contour extraction result validates the effectiveness of the proposed method. PMID- 25122606 TI - EEG compression of scalp recordings based on dipole fitting. AB - A novel technique for electroencephalogram (EEG) compression is proposed in this paper. This technique models the intrinsic dependence inherent between the different EEG channels. It is based on methods borrowed from dipole fitting that is usually used in order to find a solution to the classic problems in EEG analysis: inverse and forward problems. To compress the EEG signals, the forward model based on approximated source dipoles is first used to provide an approximation of the recorded signals. Then, (based on a smoothness factor) appropriate coding techniques are suggested to compress the residuals of the fitting process. Results show that this technique works well for different recordings and for different patients, and is even able to provide near-lossless compression for certain types of recordings. PMID- 25122607 TI - Geometric asymmetry driven Janus micromotors. AB - The production and application of nano-/micromotors is of great importance. In order for the motors to work, asymmetry in their chemical composition or physical geometry must be present if no external asymmetric field is applied. In this paper, we present a "coconut" micromotor made of platinum through the partial or complete etching of the silica templates. It was shown that although both the inner and outer surfaces are made of the same material (Pt), motion of the structure can be observed as the convex surface is capable of generating oxygen bubbles. This finding shows that not only the chemical asymmetry of the micromotor, but also its geometric asymmetry can lead to fast propulsion of the motor. Moreover, a considerably higher velocity can be seen for partially etched coconut structures than the velocities of Janus or fully etched, shell-like motors. These findings will have great importance on the design of future micromotors. PMID- 25122611 TI - Sensorimotor adaptation: multiple forms of plasticity in motor circuits. AB - One of the most striking properties of the adult central nervous system is its ability to undergo changes in function and/or structure. In mammals, learning is a major inducer of adaptive plasticity. Sensorimotor adaptation is a type of procedural--motor--learning that allows maintaining accurate movements in the presence of environmental or internal perturbations by adjusting motor output. In this work, we will review experimental evidence gathered from rodents and human and nonhuman primates pointing to possible sites of adaptation-related plasticity at different levels of organization of the nervous system. PMID- 25122609 TI - Inhibition of sphingosine kinase 2 downregulates the expression of c-Myc and Mcl 1 and induces apoptosis in multiple myeloma. AB - Sphingolipid metabolism is being increasingly recognized as a key pathway in regulating cancer cell survival and proliferation. However, very little is known about its role in multiple myeloma (MM). We investigated the potential of targeting sphingosine kinase 2 (SK2) for the treatment of MM. We found that SK2 was overexpressed in MM cell lines and in primary human bone marrow (BM) CD1381 myeloma cells. Inhibition of SK2 by SK2- specific short hairpin RNA or ABC294640 (a SK2 specific inhibitor) effectively inhibited myeloma cell proliferation and induced caspase 3-mediated apoptosis. ABC294640 inhibited primary human CD1381 myeloma cells with the same efficacy as with MM cell lines. ABC294640 effectively induced apoptosis of myeloma cells, even in the presence of BM stromal cells. Furthermore, we found that ABC294640 downregulated the expression of pS6 and directed c-Myc and myeloid cell leukemia 1 (Mcl-1) for proteasome degradation. In addition, ABC294640 increased Noxa gene transcription and protein expression. ABC294640, per se, did not affect the expression of B-cell lymphoma 2 (Bcl-2), but acted synergistically with ABT-737 (a Bcl-2 inhibitor) in inducing myeloma cell death. ABC294640 suppressed myeloma tumor growth in vivo in mouse myeloma xenograft models. Our data demonstrated that SK2 provides a novel therapeutic target for the treatment of MM.This trial was registered at www.clinicaltrials.gov as #NCT01410981. PMID- 25122610 TI - Functional characterization of the human dendritic cell immunodeficiency associated with the IRF8(K108E) mutation. AB - We have previously reported on a unique patient in whom homozygosity for a mutation at IRF8 (IRF8(K108E)) causes a severe immunodeficiency. Laboratory evaluation revealed a highly unusual myeloid compartment, remarkable for the complete absence of CD141 and CD161 monocytes, absence of CD11c1 conventional dendritic cells (DCs) and CD11c1/CD1231 plasmacytoid DCs, and striking granulocytic hyperplasia. The patient initially presented with severe disseminated mycobacterial and mucocutaneous fungal infections and was ultimately cured by cord blood transplant. Sequencing RNA from the IRF8(K108E) patient's primary blood cells prior to transplant shows not only depletion of IRF8-bound and IRF8-regulated transcriptional targets, in keeping with the distorted composition of the myeloid compartment, but also a paucity of transcripts associated with activated CD41 and CD81 T lymphocytes. This suggests that T cells reared in the absence of a functional antigen-presenting compartment in IRF8(K108E) are anergic. Biochemical characterization of the IRF8(K108E) mutant in vitro shows that loss of the positively charged side chain at K108 causes loss of nuclear localization and loss of transcriptional activity, which is concomitant with decreased protein stability, increased ubiquitination, increased small ubiquitin-like modification, and enhanced proteasomal degradation. These findings provide functional insight into the molecular basis of immunodeficiency associated with loss of IRF8. PMID- 25122614 TI - Sulfitobacter geojensis sp. nov., Sulfitobacter noctilucae sp. nov., and Sulfitobacter noctilucicola sp. nov., isolated from coastal seawater. AB - Four Gram-stain-negative, aerobic, rod-shaped bacterial strains, MM-124, MM-126, NB-68 and NB-77, were isolated from the coastal seawater or a region with a bloom of sea sparkle around Geoje island in Korea. The sequence similarity values of the 16S rRNA gene between the isolates and Sulfitobacter mediterraneus DSM 12244(T) ranged from 97.7 to 98.2%, and phylogenetic relationships suggested that they belong to a phylogenetic branch that includes the genera Sulfitobacter and Roseobacter. The isoprenoid quinone of all three novel strains was ubiquinone-10 and the major fatty acid was cis-vaccenic acid, as in other species of the genus Sulfitobacter. However, there were several differences in the morphological, physiological and biochemical characteristics among the four strains and the reference species of the genus Sulfitobacter. Moreover, the average nucleotide identity values between the three sequenced isolates and the reference strains were below 76.33, indicating that genomic variation exists between the isolates and reference strains. Chemotaxonomic characteristics together with phylogenetic affiliations and genomic distances illustrate that strains MM-124, NB-68 and NB 77 represent novel species of the genus Sulfitobacter, for which the names Sulfitobacter geojensis sp. nov. (type strain MM-124(T) =KCTC 32124(T) =JCM 18835(T)), Sulfitobacter noctilucae sp. nov. (type strain NB-68(T) =KCTC 32122(T) =JCM 18833(T)) and Sulfitobacter noctilucicola sp. nov. (type strain NB-77(T) =KCTC 32123(T) =JCM 18834(T)) are proposed. PMID- 25122612 TI - Unbiased analysis of potential targets of breast cancer susceptibility loci by Capture Hi-C. AB - Genome-wide association studies have identified more than 70 common variants that are associated with breast cancer risk. Most of these variants map to non-protein coding regions and several map to gene deserts, regions of several hundred kilobases lacking protein-coding genes. We hypothesized that gene deserts harbor long-range regulatory elements that can physically interact with target genes to influence their expression. To test this, we developed Capture Hi-C (CHi-C), which, by incorporating a sequence capture step into a Hi-C protocol, allows high resolution analysis of targeted regions of the genome. We used CHi-C to investigate long-range interactions at three breast cancer gene deserts mapping to 2q35, 8q24.21, and 9q31.2. We identified interaction peaks between putative regulatory elements ("bait fragments") within the captured regions and "targets" that included both protein-coding genes and long noncoding (lnc) RNAs over distances of 6.6 kb to 2.6 Mb. Target protein-coding genes were IGFBP5, KLF4, NSMCE2, and MYC; and target lncRNAs included DIRC3, PVT1, and CCDC26. For one gene desert, we were able to define two SNPs (rs12613955 and rs4442975) that were highly correlated with the published risk variant and that mapped within the bait end of an interaction peak. In vivo ChIP-qPCR data show that one of these, rs4442975, affects the binding of FOXA1 and implicate this SNP as a putative functional variant. PMID- 25122613 TI - High-resolution mapping of transcriptional dynamics across tissue development reveals a stable mRNA-tRNA interface. AB - The genetic code is an abstraction of how mRNA codons and tRNA anticodons molecularly interact during protein synthesis; the stability and regulation of this interaction remains largely unexplored. Here, we characterized the expression of mRNA and tRNA genes quantitatively at multiple time points in two developing mouse tissues. We discovered that mRNA codon pools are highly stable over development and simply reflect the genomic background; in contrast, precise regulation of tRNA gene families is required to create the corresponding tRNA transcriptomes. The dynamic regulation of tRNA genes during development is controlled in order to generate an anticodon pool that closely corresponds to messenger RNAs. Thus, across development, the pools of mRNA codons and tRNA anticodons are invariant and highly correlated, revealing a stable molecular interaction interlocking transcription and translation. PMID- 25122615 TI - Zhongshania aliphaticivorans sp. nov., an aliphatic hydrocarbon-degrading bacterium isolated from marine sediment, and transfer of Spongiibacter borealis Jang et al. 2011 to the genus Zhongshania as Zhongshania borealis comb. nov. AB - A Gram-staining-negative, facultatively aerobic bacterium, designated SM-2(T), was isolated from a sea-tidal flat of Yellow Sea, South Korea. Cells were catalase- and oxidase-positive motile rods with a single polar flagellum. Growth of strain SM-2(T) was observed at 10-37 degrees C (optimum, 25-30 degrees C), at pH 5.5-8.5 (optimum, pH 7.0-7.5) and in the presence of 0-11% (w/v) NaCl (optimum, 2%). Strain SM-2(T) contained ubiquinone-8 (Q-8) as the sole isoprenoid quinone and C(17:1)omega8c, summed feature 3 (comprising C(16:1)omega7c and/or iso-C(15:0) 2-OH), C(17:0) and C(18:1)omega7c as the major fatty acids. Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified lipid were identified as the major cellular polar lipids. The G+C content of the genomic DNA was 52.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SM-2(T) formed a tight phyletic lineage with Zhongshania antarctica ZS5-23(T), Zhongshania guokunii ZS6-22(T) and Spongiibacter borealis CL-AS9(T), but that S. borealis CL-AS9(T) was distinct from other species of the genus Spongiibacter. Based on 16S rRNA gene sequence similarities, strain SM-2(T) was most closely related to S. borealis CL-AS9(T), Z. antarctica ZS5-23(T) and Z. guokunii ZS6-22(T), with similarities of 99.5%, 98.9% and 98.7%, respectively, but the DNA-DNA hybridization values among these species were clearly lower than 70%. On the basis of chemotaxonomic data and molecular properties, we propose strain SM-2(T) represents a novel species of the genus Zhongshania with the name Zhongshania aliphaticivorans sp. nov. (type strain SM-2(T) =KACC 18120(T) =JCM 30138(T)). We also propose the transfer of Spongiibacter borealis Jang et al. 2011 to the genus Zhongshania as Zhongshania borealis comb. nov. (type strain CL-AS9(T) =KCCM 90094(T) =JCM 17304(T)). PMID- 25122617 TI - Determining the reach of a home-based physical activity program for older adults within the context of a randomized controlled trial. AB - Determining the reach of physical activity (PA) programs is challenging due to inconsistent reporting across studies. The purpose of this study was to document multiple indicators of program reach for a 6-month, Digital Versatile Disc (DVD) delivered home-based PA program. Radio, newspaper and direct mailing advertisements were tracked to determine costs as well as the number and representativeness of older adults exposed and responding to recruitment. It was estimated that all older adults in the recruitment area (n = 105 515) may have been exposed to at least one of the recruitment strategies--563 responded and 383 were screened as eligible. Of those that enrolled (n = 307), the DVD reached between 81% and 97% of the participants over each month within the 6 month period. Newspaper advertisements were most effective (n = 222) at a cost of $78 per participant enrolled. CONCLUSION: Using multiple indicators of reach supports the accurate calculation and generalizability of recruiting older adults into PA programs. PMID- 25122618 TI - Male smoker and non-smoker responses to television advertisements on the harms of secondhand smoke in China, India and Russia. AB - Mass media campaigns can play an important role in strengthening support for smoke-free policies and reducing exposure to secondhand smoke (SHS). Identifying anti-SHS advertisements that are effective in diverse cultural contexts may allow for resource sharing in low- and middle-income countries. A convenience sample of 481 male cigarette smokers and non-smokers in three high tobacco burden and culturally dissimilar countries (India, China and Russia) viewed and rated five anti-SHS ads. Multivariate logistic regression analyses were conducted for 'Message Acceptance', 'Negative Emotion', 'Perceived Effectiveness' and 'Behavioral Intentions'. Smokers and non-smokers in all countries consistently rated the strong graphic, health harm ads as the most effective, and the 'informational' ad as the least effective overall: the graphic ad 'Baby Alive' was at least 1.8 times more likely than the informational ad 'Smoke-free works' to receive positive ratings on all four outcomes (all P < 0.001). Graphic, health harm messages about SHS exposure have the greatest universal appeal and are the most effective in motivating changes in behavioral intentions. Similarity in reactions between smokers and non-smokers, and across countries, suggests that resource sharing and the use of a single graphic ad targeted at smokers and non smokers would be cost-efficient strategies. PMID- 25122616 TI - Feasibility and reliability of pocket-size ultrasound examinations of the pleural cavities and vena cava inferior performed by nurses in an outpatient heart failure clinic. AB - BACKGROUND: Routine assessment of volume state by ultrasound may improve follow up of heart failure patients. AIMS: We aimed to study the feasibility and reliability of focused pocket-size ultrasound examinations of the pleural cavities and the inferior vena cava performed by nurses to assess volume state at an outpatient heart failure clinic. METHODS: Ultrasound examinations were performed in 62 included heart failure patients by specialized nurses with a pocket-size imaging device (PSID). Patients were then re-examined by a cardiologist with a high-end scanner for reference within 1 h. Specialized nurses were able to obtain and interpret images from both pleural cavities and the inferior vena cava and estimate the volume status in all patients. RESULTS: Time consumption for focused ultrasound examination was median 5 min. In total 26 patients had any kind of pleural effusion (in 39 pleural cavities) by reference. The sensitivity, specificity, positive and negative predictive values were high, all >= 92%. The correlations with reference were high for all measurements, all r >= 0.79. Coefficients of variation for end-expiratory dimension of inferior vena cava and quantification of pleural effusion were 10.8% and 12.7%, respectively. CONCLUSIONS: Specialized nurses were, after a dedicated training protocol, able to obtain reliable recordings of both pleural cavities and the inferior vena cava by PSID and interpret the images in a reliable way. Implementing focused ultrasound examinations to assess volume status by nurses in an outpatient heart failure clinic may improve diagnostics, and thus improve therapy. PMID- 25122619 TI - Understanding something that is remotely sensible, scaling active chlorophyll fluorescence from leaves to canopies at ranges of ~50 metres. PMID- 25122620 TI - Seasonal changes in carbon and nitrogen compound concentrations in a Quercus petraea chronosequence. AB - Forest productivity declines with tree age. This decline may be due to changes in metabolic functions, resource availability and/or changes in resource allocation (between growth, reproduction and storage) with tree age. Carbon and nitrogen remobilization/storage processes are key to tree growth and survival. However, studies of the effects of tree age on these processes are scarce and have not yet considered seasonal carbon and nitrogen variations in situ. This study was carried out in a chronosequence of sessile oak (Quercus petraea Liebl.) for 1 year to survey the effects of tree age on the seasonal changes of carbon and nitrogen compounds in several tree compartments, focusing on key phenological stages. Our results highlight a general pattern of carbon and nitrogen function at all tree ages, with carbon reserve remobilization at budburst for growth, followed by carbon reserve formation during the leafy season and carbon reserve use during winter for maintenance. The variation in concentrations of nitrogen compounds shows less amplitude than that of carbon compounds. Storage as proteins occurs later, and mainly depends on leaf nitrogen remobilization and root uptake in autumn. We highlight several differences between tree age groups, in particular the loss of carbon storage function of fine and medium-sized roots with tree ageing. Moreover, the pattern of carbon compound accumulation in branches supports the hypothesis of a preferential allocation of carbon towards growth until the end of wood formation in juvenile trees, at the expense of the replenishment of carbon stores, while mature trees start allocating carbon to storage right after budburst. Our results demonstrate that at key phenological stages, physiological and developmental functions differ with tree age, and together with environmental conditions, influence the carbon and nitrogen concentration variations in sessile oaks. PMID- 25122621 TI - CecropinXJ, a silkworm antimicrobial peptide, induces cytoskeleton disruption in esophageal carcinoma cells. AB - Antimicrobial peptides exist in the non-specific immune system of organism and participate in the innate host defense of each species. CecropinXJ, a cationic antimicrobial peptide, possesses potent anticancer activity and acts preferentially on cancer cells instead of normal cells, but the mechanism of cancer cell death induced by cecropinXJ remains largely unknown. This study was performed to investigate the cytoskeleton-disrupting effects of cecropinXJ on human esophageal carcinoma cell line Eca109 using scanning electron microscopy observation, fluorescence imaging, cell migration and invasion assays, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT PCR) analysis. The electronic microscope and fluorescence imaging observation suggested that cecropinXJ could result in morphological changes and induce damage to microtubules and actin of Eca109 cells in a dose-dependent manner. The cell migration and invasion assays demonstrated that cecropinXJ could inhibit migration and invasion of tumor cells. Western blot and qRT-PCR analysis showed that there was obvious correlation between microtubule depolymerization and actin polymerization induced by cecropinXJ. Moreover, cecropinXJ might also cause decreased expression of alpha-actin, beta-actin, gamma-actin, alpha-tubulin, and beta-tubulin genes in concentration- and time-dependent manners. In summary, this study indicates that cecropinXJ triggers cytotoxicity in Eca109 cells through inducing the cytoskeleton destruction and regulating the expression of cytoskeleton proteins. This cecropinXJ-mediated cytoskeleton-destruction effect is instrumental in our understanding of the detailed action of antimicrobial peptides in human cancer cells and cecropinXJ might be a potential therapeutic agent for the treatment of cancer in the future. PMID- 25122622 TI - Beam-induced motion correction for sub-megadalton cryo-EM particles. AB - In electron cryo-microscopy (cryo-EM), the electron beam that is used for imaging also causes the sample to move. This motion blurs the images and limits the resolution attainable by single-particle analysis. In a previous Research article (Bai et al., 2013) we showed that correcting for this motion by processing movies from fast direct-electron detectors allowed structure determination to near atomic resolution from 35,000 ribosome particles. In this Research advance article, we show that an improved movie processing algorithm is applicable to a much wider range of specimens. The new algorithm estimates straight movement tracks by considering multiple particles that are close to each other in the field of view, and models the fall-off of high-resolution information content by radiation damage in a dose-dependent manner. Application of the new algorithm to four data sets illustrates its potential for significantly improving cryo-EM structures, even for particles that are smaller than 200 kDa. PMID- 25122623 TI - Cryo-EM enters a new era. AB - Advances in detector hardware and image-processing software have led to a revolution in the use of electron cryo-microscopy to determine complex molecular structures at high resolution. PMID- 25122625 TI - Advancing research. AB - eLife has introduced a new type of article-the Research Advance-that allows the authors of an eLife paper to publish results that build on their original research paper. PMID- 25122626 TI - Strategies to Promote Cultural Competence in Distance Education. AB - Cultural competence is a mainstay in health care and nursing education. With the expansion in the number of distance-based nursing programs across the country, innovative teaching methods for distance learning faculty are required to instill cultural competence in students. Faculty must be deliberate when planning distance-based learning activities that incorporate cultural experiences. This article describes several such strategies including the creative use of blogging, recorded lectures, the online synchronous classroom, social media, and cultural immersion projects. These methods capitalize on existing information technologies and offer distance-based students the opportunity to connect with one another, as well as develop the awareness, sensitivity, and respect that is required when providing culturally competent care. These teaching methods are modifiable to meet the teaching and learning needs of the faculty and the students, thereby allowing educators to support the integration of cultural competence into patient care for distance students. PMID- 25122624 TI - Complexin inhibits spontaneous release and synchronizes Ca2+-triggered synaptic vesicle fusion by distinct mechanisms. AB - Previously we showed that fast Ca(2+)-triggered vesicle fusion with reconstituted neuronal SNAREs and synaptotagmin-1 begins from an initial hemifusion-free membrane point contact, rather than a hemifusion diaphragm, using a single vesicle-vesicle lipid/content mixing assay (Diao et al., 2012). When complexin-1 was included, a more pronounced Ca(2+)-triggered fusion burst was observed, effectively synchronizing the process. Here we show that complexin-1 also reduces spontaneous fusion in the same assay. Moreover, distinct effects of several complexin-1 truncation mutants on spontaneous and Ca(2+)-triggered fusion closely mimic those observed in neuronal cultures. The very N-terminal domain is essential for synchronization of Ca(2+)-triggered fusion, but not for suppression of spontaneous fusion, whereas the opposite is true for the C-terminal domain. By systematically varying the complexin-1 concentration, we observed differences in titration behavior for spontaneous and Ca(2+)-triggered fusion. Taken together, complexin-1 utilizes distinct mechanisms for synchronization of Ca(2+)-triggered fusion and inhibition of spontaneous fusion. PMID- 25122627 TI - Managing the ethical challenges of next-generation sequencing in genomic medicine. AB - INTRODUCTION: Next-generation sequencing (NGS) is transforming the conduct of genetic research and diagnostic investigation. This creates new challenges as it generates additional information, including unsought and unwanted information. Nevertheless, this information must be deliberately managed-interpreted, disclosed and then either stored or destroyed. AREAS OF AGREEMENT: Handling the process of consent to exome or genome sequencing should include discussion about the possible detection of variants of uncertain significance (VUSs) or incidental findings (IFs) that the patient may prefer not to hear about. A plan should be drawn up that specifies whether and how the patient would be recontacted in the future with new interpretations. AREAS OF CONTROVERSY: There is an active debate about which IFs or VUSs should be disclosed to the patient when an exome or genome sequence has been performed, or whether all findings of any possible relevance should always be disclosed. How this is managed has important implications for the initial explanation of the test to the patient and the process of consent. The assumption is often made that all sequence information should be stored, but this may not be sustainable or useful. GROWING POINTS: Efforts are being made to build a consensus on what 'incidental' information should be disclosed. These policy questions are being addressed in many centres and practices are evolving rapidly. AREAS TIMELY FOR DEVELOPING RESEARCH: Those interested in genetics, public health, bioethics and medical ethics may wish to debate these issues and influence future practice in both genetic research and genetic diagnostic services. PMID- 25122628 TI - Bed rest promotes reductions in walking speed, functional parameters, and aerobic fitness in older, healthy adults. AB - CONTEXT: The exact relationship between the bed rest-induced loss of skeletal muscle and reductions in muscle strength and physical performance in the older individuals is still unclear. OBJECTIVE: We examined the effect of 10 days of bed rest on changes in regional body composition, muscle strength, and functional status, and the relationship between these variables in older individuals. DESIGN, PARTICIPANTS, AND INTERVENTION: Regional body composition was measured using dual energy x-ray absorptiometry. We also determined changes in leg strength and several indices of functional status, including walking speed. RESULTS: Body weight, body mass index, and total and lower extremity lean mass decreased with bed rest. There were also significant reductions in knee extension one repetition maximum, isometric knee extension, knee extension 60 degrees concentric, stair ascent time, stair ascent power, stair descent time, VO2 max, floor transfer test, 5-minute walk time, and chair stand. The overall change in total and lower extremity lean mass was also directly related to bed rest-induced reductions in one repetition maximum knee extension. CONCLUSIONS: Bed rest promoted overall declines in muscle mass, muscle strength, and physical function in older individuals. The changes in lean tissue were closely correlated with the bed rest-induced decline of muscle strength. PMID- 25122629 TI - Ultrasound-guided percutaneous needle electrolysis in chronic lateral epicondylitis: short-term and long-term results. AB - BACKGROUND: Ultrasound (US)-guided percutaneous needle electrolysis (PNE) is a novel minimally invasive approach which consists of the application of a galvanic current through an acupuncture needle. OBJECTIVE: To evaluate the clinical and ultrasonographic effectiveness of a multimodal programme (PNE, eccentric exercise (EccEx) and stretching) in the short term for patients with chronic lateral epicondylitis, and to determine whether the clinical outcomes achieved decline over time. METHODS: A one-way repeated measures study was performed in a clinical setting in 36 patients presenting with lateral epicondylitis. The patients received one session of US-guided PNE per week over 4-6 weeks, associated with a home programme of EccEx and stretching. The main outcome measures were severity of pain, disability (Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire), structural tendon changes (US), hypervascularity and patients' perceptions of overall outcome. Measurements at 6, 26 and 52 weeks follow-up included recurrence rates (increase in severity of pain or disability compared with discharge), perception of overall outcome and success rates. RESULTS: All outcome measures registered significant improvements between pre-intervention and discharge. Most patients (n=30, 83.3%) rated the overall outcome as 'successful' at 6 weeks. The ultrasonographic findings showed that the hypoechoic regions and hypervascularity of the extensor carpi radialis brevis changed significantly. At 26 and 52 weeks, all participants (n=32) perceived a 'successful' outcome. Recurrence rates were null after discharge and at follow-up at 6, 26 and 52 weeks. CONCLUSIONS: Symptoms and degenerative structural changes of chronic lateral epicondylitis are reduced after US-guided PNE associated with EccEx and stretching, with encouragingly low recurrences in the mid to long term. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02085928. PMID- 25122630 TI - The epidemiological and clinical characteristics of diarrhea associated with enteropathogenic, enteroaggregative and diffuse-adherent Escherichia coli in Egyptian children. AB - A total of 220 enteroadherent Escherichia coli were identified from 729 Egyptian children with diarrhea using the HEp-2 adherence assay. Enteropathogenic E.coli (EPEC = 38) was common among children <6 months old and provoked vomiting, while diffuse-adhering E.coli (DAEC = 109) induced diarrheal episodes of short duration, and enteroaggregative E.coli (EAEC = 73) induced mild non-persistent diarrhea. These results suggest that EPEC is associated with infantile diarrhea in Egyptian children. PMID- 25122632 TI - Two-year carcinogenicity study in rats with a nonnucleoside reverse transcriptase inhibitor. AB - Administration of lersivirine, a nonnucleotide reverse transcriptase inhibitor, daily by oral gavage to Sprague-Dawley rats for up to 2 yr was associated with decreased survival, decreased body weights, and an increase in neoplasms and related proliferative lesions in the liver, thyroid, kidney, and urinary bladder. Thyroid follicular adenoma and carcinoma, the associated thyroid follicular hypertrophy/hyperplasia, hepatocellular adenoma/adenocarcinoma, altered cell foci, and hepatocellular hypertrophy were consistent with lersivirine-related induction of hepatic microsomal enzymes. Renal tubular adenoma and renal tubular hyperplasia were attributed to the lersivirine-related exacerbation of chronic progressive nephropathy (CPN), while urinary bladder hyperplasia and transitional cell carcinoma in the renal pelvis and urinary bladder were attributed to urinary calculi. Renal tubular neoplasms associated with increased incidence and severity of CPN, neoplasms of transitional epithelium attributed to crystalluria, and thyroid follicular and hepatocellular neoplasms related to hepatic enzyme induction have low relevance for human risk assessment. PMID- 25122631 TI - Tel1ATM dictates the replication timing of short yeast telomeres. AB - Telomerase action is temporally linked to DNA replication. Although yeast telomeres are normally late replicating, telomere shortening leads to early firing of subtelomeric DNA replication origins. We show that double-strand breaks flanked by short telomeric arrays cause origin firing early in S phase at late replicating loci and that this effect on origin firing time is dependent on the Tel1(ATM) checkpoint kinase. The effect of Tel1(ATM) on telomere replication timing extends to endogenous telomeres and is stronger than that elicited by Rif1 loss. These results establish that Tel1(ATM) specifies not only the extent but also the timing of telomerase recruitment. PMID- 25122633 TI - Stability study of carboplatin infusion solutions in 0.9% sodium chloride in polyvinyl chloride bags. AB - BACKGROUND AND PURPOSE: Carboplatin is a platinum-containing compound with efficacy against various malignancies. The physico-chemical stability of carboplatin in dextrose 5% water (D5W) has been thoroughly studied; however, there is a paucity of stability data in clinically relevant 0.9% sodium chloride infusion solutions. The manufacturer's limited stability data in sodium chloride solutions hampers the flexibility of carboplatin usage in oncology patients. Hence, the purpose of this study is to determine the physical and chemical stability of carboplatin-sodium chloride intravenous solutions under different storage conditions. METHODS: The physico-chemical stability of 0.5 mg/mL, 2.0 mg/mL, and 4.0 mg/mL carboplatin-sodium chloride solutions prepared in polyvinyl chloride bags was determined following storage at room temperature under ambient fluorescent light and under refrigeration in the dark. Concentrations of carboplatin were measured at predetermined time points up to seven days using a stability-indicating high-performance liquid chromatography method. RESULTS: All tested solutions were found physically stable for at least seven days. The greatest chemical stability was observed under refrigerated storage conditions. At 4C, all tested solutions were found chemically stable for at least seven days, with nominal losses of <=6%. Following storage at room temperature exposed to normal fluorescent light, the chemical stability of 0.5 mg/mL, 2.0 mg/mL, and 4.0 mg/mL solutions was three days, five days, and seven days, respectively. CONCLUSION: The extended physico-chemical stability of carboplatin prepared in sodium chloride reported herein permits advance preparation of these admixtures, facilitating pharmacy utility and operations. Since no antibacterial preservative is contained within these carboplatin solutions, we recommend storage, when prepared under specified aseptic conditions, no greater than 24 h at room temperature or three days under refrigeration. PMID- 25122634 TI - Compliance with National Comprehensive Cancer Network anti-emesis guidelines in a Community Hospital Cancer Center. AB - OBJECTIVE: Nausea and vomiting are common adverse events exhibited by patients receiving chemotherapy. Prophylactic use of anti-emetic agents has been shown to reduce chemotherapy-induced nausea and vomiting. Compliance with the National Comprehensive Cancer Network anti-emesis guidelines (Version 1.2013) by practitioners in a community out-patient hospital (Blount Memorial Hospital) has been reviewed and the results are presented herein. DESIGN: Retrospective study of patients receiving their first cycle of chemotherapy. PATIENTS: A total of 487 patients were reviewed from January 2005 to July 2012. In total, 70 patients were categorized in the high-risk category, 292 patients were categorized in the moderate-risk category, 60 patients were categorized in the low-risk category, and 65 patients were categorized in the minimal-risk category as per the National Comprehensive Cancer Network guidelines. Included patients were being administered the first cycle of their first treatment at Blount Memorial Hospital. DATA: Data were collected retrospectively from patient chemotherapy dispensing folders. RESULTS: In all, 63% of the patients received appropriate anti-emetic prophylaxis medications as per the National Comprehensive Cancer Network guidelines. Post-comparison between outcomes based on the risk category showed that patients in the moderate-risk category were most likely (91%) and patients in the low-risk category were least likely (6.67%) to receive appropriate anti-emetic prophylaxis as per the National Comprehensive Cancer Network guidelines. CONCLUSION: Overall compliance with guidelines is acceptable. Patients in the moderate risk category are most likely to receive appropriate anti-emetic prophylaxis. PMID- 25122635 TI - Tranexamic acid for surgical bleeding. PMID- 25122636 TI - Deficient human beta-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection. AB - Genital tract infection and reduced sperm motility are considered two pivotal etiological factors for male infertility associated with leukocytospermia and asthenozoospermia, respectively. We demonstrate that the amount of human beta defensin 1 (DEFB1) in sperm from infertile men exhibiting either leukocytospermia or asthenozoospermia, both of which are associated with reduced motility and reduced bactericidal activity in sperm, is much lower compared to that in normal fertile sperm. Interference with DEFB1 function also decreases both motility and bactericidal activity in normal sperm, whereas treatment with recombinant DEFB1 markedly restores DEFB1 expression, bactericidal activity, sperm quality, and egg penetrating ability in sperm from both asthenozoospermia and leukocytospermia patients. DEFB1 interacts with chemokine receptor type 6 (CCR6) in sperm and triggers Ca(2+) mobilization, which is important for sperm motility. Interference with CCR6 function also reduces motility and bactericidal activity of normal sperm. The present finding explains a common defect in male infertility associated with both asthenozoospermia and leukocytospermia, indicating a dual role of DEFB1 in defending male fertility. These results also suggest that the expression of DEFB1 and CCR6 may have diagnostic potential and that treatment of defective sperm with recombinant DEFB1 protein may be a feasible therapeutic approach for male infertility associated with poor sperm motility and genital tract infection. PMID- 25122638 TI - A single localized dose of enzyme-responsive hydrogel improves long-term survival of a vascularized composite allograft. AB - Currently, systemic immunosuppression is used in vascularized composite allotransplantation (VCA). This treatment has considerable side effects and reduces the quality of life of VCA recipients. We loaded the immunosuppressive drug tacrolimus into a self-assembled hydrogel, which releases the drug in response to proteolytic enzymes that are overexpressed during inflammation. A one time local injection of the tacrolimus-laden hydrogel significantly prolonged graft survival in a Brown Norway-to-Lewis rat hindlimb transplantation model, leading to a median graft survival of >100 days compared to 33.5 days in tacrolimus only-treated recipients. Control groups with no treatment or hydrogel only showed a graft survival of 11 days. Histopathological evaluation, including anti-graft antibodies and complement C3, revealed significantly reduced immune responses in the tacrolimus-hydrogel group compared with tacrolimus only. In conclusion, a single-dose local injection of an enzyme-responsive tacrolimus hydrogel is capable of preventing VCA rejection for >100 days in a rat model and may offer a new approach for immunosuppression in VCA. PMID- 25122637 TI - Lymph node fibroblastic reticular cell transplants show robust therapeutic efficacy in high-mortality murine sepsis. AB - Sepsis is an aggressive inflammatory syndrome and a global health burden estimated to kill 7.3 million people annually. Single-target molecular therapies have not addressed the multiple disease pathways triggered by septic injury. Cell therapies might offer a broader set of mechanisms of action that benefit complex, multifocal disease processes. We describe a population of immune-specialized myofibroblasts derived from lymph node tissue, termed fibroblastic reticular cells (FRCs). Because FRCs have an immunoregulatory function in lymph nodes, we hypothesized that ex vivo-expanded FRCs would control inflammation when administered therapeutically. Indeed, a single injection of ex vivo-expanded allogeneic FRCs reduced mortality in mouse models of sepsis when administered at early or late time points after septic onset. Mice treated with FRCs exhibited lower local and systemic concentrations of proinflammatory cytokines and reduced bacteremia. When administered 4 hours after induction of lipopolysaccharide endotoxemia, or cecal ligation and puncture (CLP) sepsis in mice, FRCs reduced deaths by at least 70%. When administered late in disease (16 hours after CLP), FRCs still conveyed a robust survival advantage (44% survival compared to 0% for controls). FRC therapy was dependent on the metabolic activity of nitric oxide synthase 2 (NOS2) as the primary molecular mechanism of drug action in the mice. Together, these data describe a new anti-inflammatory cell type and provide preclinical evidence for therapeutic efficacy in severe sepsis that warrants further translational study. PMID- 25122641 TI - Translational pain research: Lessons from genetics and genomics. AB - Pharmacological, surgical, psychological, and alternative medicine approaches for the treatment of chronic pain, including neuropathic pain, provide only partial relief for most patients, with the efficacy of existing medications often blunted by dose-limiting side effects arising from drug actions on cells outside the pain signaling axis. The development of more effective treatments for pain- particularly chronic pain states such as neuropathic pain--has been hampered by lack of predictive animal models and biomarkers, variation in pain characteristics between patients or on a day-to-day basis for single patients, patient stratification on the basis of symptoms rather than mechanism, and a high rate of placebo responses. We discuss genetic and genomic approaches to translational pain research. We review examples of the identification and validation of human pain targets through rodent genome-wide association studies (GWAS) and global mRNA expression studies, functional screening in flies and mice, human GWAS and whole-exome sequencing studies, and the targeted candidate gene approach. These and other emerging genetic and genomic strategies are likely to facilitate the development of new, more effective pain therapeutics. PMID- 25122639 TI - Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses. AB - Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted. PMID- 25122642 TI - Does a single dose of intravenous dexamethasone reduce Symptoms in Emergency department patients with low Back pain and RAdiculopathy (SEBRA)? A double-blind randomised controlled trial. AB - OBJECTIVE: To assess the effect of a single dose of intravenous dexamethasone in addition to routine treatment on visual analogue scale (VAS) pain scores at 24 h in emergency department (ED) patients with low back pain with radiculopathy (LBPR). METHODS: Double-blind randomised controlled trial of 58 adult ED patients with LBPR, conducted in one tertiary and one urban ED. The intervention was 8 mg of intravenous dexamethasone (or placebo) in addition to current routine care. The primary outcome was the change in VAS pain scores between presentation and 24 h. Secondary outcomes included VAS pain scores at 6 weeks, ED length of stay (EDLOS), straight leg raise (SLR) angles and Oswestry functional scores. RESULTS: Patients treated with dexamethasone had a 1.86 point (95% CI 0.31 to 3.42, p=0.019) greater reduction in VAS pain scores at 24 h than placebo (dexamethasone: -2.63 (95% CI -3.63 to -1.63) versus placebo: -0.77 (95% CI -2.04 to 0.51)). At 6 weeks, both groups had similar significant and sustained decrease in VAS scores compared with baseline. Patients receiving dexamethasone had a significantly shorter EDLOS (median: 3.5 h vs 18.8 h, p=0.049) and improved SLR angle at discharge (14.7 degrees , p=0.040). There was no difference in functional scores. CONCLUSIONS: In patients with LBPR, a single dose of intravenous dexamethasone in addition to routine management improved VAS pain scores at 24 h, but this effect was not statistically significant at 6 weeks. Dexamethasone may reduce EDLOS and can be considered as a safe adjunct to standard treatment. TRIAL REGISTRATION NUMBER: ACTRN12611001020976. PMID- 25122643 TI - Analysis of mandibular structure using 3D facial computed tomography. AB - OBJECTIVE: This study measured and analyzed the position and dimension of genial tubercle (GT) and mental foramen (MF) STUDY DESIGN: Retrospective chart review study. SETTING: Tertiary care teaching hospital. SUBJECTS AND METHODS: Two hundred ten subjects were included who received 3-dimensional (3D) facial computed tomography (CT), and the GT and MF were evaluated. Subjects were divided into 4 groups by gender and skeletal type. Seven variables were measured: (1) height of GT (GTH), (2) width of GT (GTW), (3) distance from apices of lower incisors to superior border of GT (LI-SGT), (4) distance from inferior border of GT to inferior border of mandible (IGT-IBM), (5) thickness of anterior mandible (MT), (6) distance from symphysis of mandible to MF (S-MF), and (7) distance from superior border of GT to inferior border of mandible (SGT-IBM). RESULTS: All the parameters showed marked differences in individuals. Class I males showed longer GTH, MT, and SGT-IBM than class I females (P < .05). IGT-IBM and S-MF were longer in class II males than in class I females (P < .05). LI-SGT and IGT-IBM also showed personal variation. CONCLUSION: Anatomical features of mandibular structures showed individual variations. GTH, IGT-IBM, MT, S-MF, and SGT-IBM also showed differences between the groups. PMID- 25122644 TI - High-salt intake induces cardiomyocyte hypertrophy in rats in response to local angiotensin II type 1 receptor activation. AB - Many studies have shown that risk factors that are independent of blood pressure (BP) can contribute to the development of cardiac hypertrophy (CH). Among these factors, high-salt (HS) intake was prominent. Although some studies have attempted to elucidate the role of salt in the development of this disease, the mechanisms by which salt acts are not yet fully understood. Thus, the aim of this study was to better understand the mechanisms of CH and interstitial fibrosis (IF) caused by HS intake. Male Wistar rats were divided into 5 groups according to diet [normal salt (NS; 1.27% NaCl) or HS (8% NaCl)] and treatment [losartan (LOS) (HS+LOS group), hydralazine (HZ) (HS+HZ group), or N-acetylcysteine (NAC) (HS+NAC group)], which was given in the drinking water. Tail-cuff BP, transverse diameter of the cardiomyocyte, IF, angiotensin II type 1 receptor (AT1) gene and protein expression, serum aldosterone, cardiac angiotensin II, cardiac thiobarbituric acid-reactive substances, and binding of conformation-specific anti-AT1 and anti-angiotensin II type 2 receptor (AT2) antibodies in the 2 ventricles were measured. Based on the left ventricle transverse diameter data, the primary finding was the occurrence of significant BP-independent CH in the HS+HZ group (96% of the HS group) and a partial or total prevention of such hypertrophy via treatment with NAC or LOS (81% and 67% of the HS group, respectively). The significant total or partial prevention of IF using all 3 treatments (HS+HZ, 27%; HS+LOS, 27%; and HS+NAC, 58% of the HS group, respectively), and an increase in the AT1 gene and protein expression and activity in groups that developed CH, confirmed that CH occurred via the AT1 in this experimental model. Thus, this study unveiled some relevant previously unknown mechanisms of CH induced by chronic HS intake in Wistar rats. The link of oxidative stress with CH in our experimental model is very interesting and stimulates further evaluation for its full comprehension. PMID- 25122640 TI - Lost but making progress--Where will new analgesic drugs come from? AB - There is a critical need for effective new pharmacotherapies for pain. The paucity of new drugs successfully reaching the clinic calls for a reassessment of current analgesic drug discovery approaches. Many points early in the discovery process present significant hurdles, making it critical to exploit advances in pain neurobiology to increase the probability of success. In this review, we highlight approaches that are being pursued vigorously by the pain community for drug discovery, including innovative preclinical pain models, insights from genetics, mechanistic phenotyping of pain patients, development of biomarkers, and emerging insights into chronic pain as a disorder of both the periphery and the brain. Collaborative efforts between pharmaceutical, academic, and public entities to advance research in these areas promise to de-risk potential targets, stimulate investment, and speed evaluation and development of better pain therapies. PMID- 25122646 TI - Glycine stimulates protein synthesis and inhibits oxidative stress in pig small intestinal epithelial cells. AB - Glycine has recently been classified as a nutritionally essential amino acid for maximal growth in young pigs. Currently, little is known about the metabolism or function of glycine in the neonatal intestine. This work was conducted to test the hypothesis that glycine has a protective effect against oxidative stress in intestinal epithelial cells. Jejunal enterocytes isolated from newborn pigs were cultured in the presence of 0.0-2 mmol/L glycine for measurements of glycine metabolism, cell proliferation, protein turnover, apoptosis, and antioxidative response. Compared with 0.0-0.5 mmol/L glycine, 1.0 mmol/L glycine enhanced (P < 0.05) cell growth (by 8-24% on day 2 and by 34-224% on day 4, respectively) and protein synthesis (by 36-419%) while reducing (P < 0.05) protein degradation (by 7-28%). This effect of glycine was associated with activation of the mammalian target of rapamycin signaling pathway in enterocytes. By using a model of oxidative stress induced by 30 MUmol/L 4-hydroxynonenal (4-HNE), which was assessed by flow cytometry analysis, 1.0 mmol/L glycine inhibited (P < 0.05) activation of caspase 3 by 25% and attenuated (P < 0.05) 4-HNE-induced apoptosis by 38% in intestinal porcine epithelial cell line 1 cells through promotion of reduced glutathione synthesis and expression of glycine transporter 1 while reducing the activation of extracellular signal-regulated kinases, c-Jun amino terminal kinases, and p38 protein in the mitogen-activated protein kinase signaling pathway. These novel findings provide a biochemical mechanism for the use of dietary glycine to improve intestinal health in neonates under conditions of oxidative stress and glycine deficiency. PMID- 25122645 TI - MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers. AB - BACKGROUND: MicroRNAs (miRNAs) regulate genes in animals and plants and can be synthesized endogenously. In milk, miRNAs are encapsulated in exosomes, thereby conferring protection against degradation and facilitating uptake by endocytosis. The majority of bovine miRNAs have nucleotide sequences complementary to human gene transcripts, suggesting that miRNAs in milk might regulate human genes. OBJECTIVES: We tested the hypotheses that humans absorb biologically meaningful amounts of miRNAs from nutritionally relevant doses of milk, milk-borne miRNAs regulate human gene expression, and mammals cannot compensate for dietary miRNA depletion by endogenous miRNA synthesis. METHODS: Healthy adults (3 men, 2 women; aged 26-49 y) consumed 0.25, 0.5, and 1.0 L of milk in a randomized crossover design. Gene expression studies and milk miRNA depletion studies were conducted in human cell cultures and mice, respectively. For comparison, feeding studies with plant miRNAs from broccoli were conducted in humans. RESULTS: Postprandial concentration time curves suggest that meaningful amounts of miRNA (miR)-29b and miR-200c were absorbed; plasma concentrations of miR-1 did not change (negative control). The expression of runt-related transcription factor 2 (RUNX2), a known target of miR-29b, increased by 31% in blood mononuclear cells after milk consumption compared with baseline. When milk exosomes were added to cell culture media, mimicking postprandial concentrations of miR-29b and miR-200c, reporter gene activities significantly decreased by 44% and 17%, respectively, compared with vehicle controls in human embryonic kidney 293 cells. When C57BL/6J mice were fed a milk miRNA-depleted diet for 4 wk, plasma miR-29b concentrations were significantly decreased by 61% compared with miRNA-sufficient controls, i.e., endogenous synthesis did not compensate for dietary depletion. Broccoli sprout feeding studies were conducted as a control and elicited no detectable increase in Brassica-specific miRNAs. CONCLUSION: We conclude that miRNAs in milk are bioactive food compounds that regulate human genes. PMID- 25122648 TI - Low doses of eicosapentaenoic acid and docosahexaenoic acid from fish oil dose dependently decrease serum triglyceride concentrations in the presence of plant sterols in hypercholesterolemic men and women. AB - Plant sterols (PSs) lower LDL cholesterol (LDL-C) concentrations, whereas the n-3 (omega-3) fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglyceride (TG) concentrations. Incorporating both PSs and EPA+DHA from fish oil (FO) in a single food format was expected to beneficially affect 2 blood lipid risk factors. The aim of this study was to investigate the dose response relation between low doses (<2 g/d) of EPA+DHA from FO, incorporated in a low-fat PS-enriched spread, and TG concentrations. In addition, effects on LDL C were investigated. The study was designed as a randomized, double-blind, placebo-controlled parallel study. After a 4-wk run-in period, subjects were randomly assigned to consume either a control (C) spread (no PSs, no FO) or 1 of 4 intervention spreads containing a fixed amount of PSs (2.5 g/d) and varying amounts of FO (0.0, 0.9, 1.3, and 1.8 g/d of EPA+DHA) for 4 wk. Before and after the intervention, fasting blood samples were drawn for measuring serum lipids and EPA and DHA in erythrocyte membranes. In total, 85 hypercholesterolemic men and 247 women with a mean age of 57.9 y (range: 25-74 y) were included. Eighteen subjects dropped out during the study. At baseline, mean TG and LDL-C concentrations were 1.09 and 4.00 mmol/L, respectively. After the intervention, a significant dose-response relation for the TG-lowering effect of EPA+DHA [betaln (TG) = -0.07 mmol/L per gram of EPA+DHA; P < 0.01] was found. Compared with the C group, TG concentrations were 9.3-16.2% lower in the different FO groups (P < 0.05 for all groups). LDL-C concentrations were 11.5-14.7% lower in the different PS groups than in the C group (P < 0.01 for all groups). EPA and DHA in erythrocyte membranes were dose-dependently higher after FO intake than after the C spread, indicating good compliance. Consumption of a low-fat spread enriched with PSs and different low doses of n-3 fatty acids from FO decreased TG concentrations in a dose-dependent manner and decreased LDL-C concentrations. This trial was registered at clinicaltrials.gov as NCT01313988. PMID- 25122649 TI - Computer modeling of obesity links theoretical energetic measures with experimental measures of fuel use for lean and obese men. AB - The goal of this research was to use a computational model of human metabolism to predict energy metabolism for lean and obese men. The model is composed of 6 state variables representing amino acids, muscle protein, visceral protein, glucose, triglycerides, and fatty acids (FAs). Differential equations represent carbohydrate, amino acid, and FA uptake and output by tissues based on ATP creation and use for both lean and obese men. Model parameterization is based on data from previous studies. Results from sensitivity analyses indicate that model predictions of resting energy expenditure (REE) and respiratory quotient (RQ) are dependent on FA and glucose oxidation rates with the highest sensitivity coefficients (0.6, 0.8 and 0.43, 0.15, respectively, for lean and obese models). Metabolizable energy (ME) is influenced by ingested energy intake with a sensitivity coefficient of 0.98, and a phosphate-to-oxygen ratio by FA oxidation rate and amino acid oxidation rate (0.32, 0.24 and 0.55, 0.65 for lean and obese models, respectively). Simulations of previously published studies showed that the model is able to predict ME ranging from 6.6 to 9.3 with 0% differences between published and model values, and RQ ranging from 0.79 to 0.86 with 1% differences between published and model values. REEs >7 MJ/d are predicted with 6% differences between published and model values. Glucose oxidation increases by ~0.59 mol/d, RQ increases by 0.03, REE increases by 2 MJ/d, and heat production increases by 1.8 MJ/d in the obese model compared with lean model simulations. Increased FA oxidation results in higher changes in RQ and lower relative changes in REE. These results suggest that because fat mass is directly related to REE and rate of FA oxidation, body fat content could be used as a predictor of RQ. PMID- 25122647 TI - Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet. AB - BACKGROUND: Biotin functions as a cofactor for several carboxylase enzymes with key roles in metabolism. At present, the dietary requirement for biotin is unknown and intake recommendations are provided as Adequate Intakes (AIs). The biotin AI for adults and pregnant women is 30 MUg/d, whereas 35 MUg/d is recommended for lactating women. However, pregnant and lactating women may require more biotin to meet the demands of these reproductive states. OBJECTIVE: The current study sought to quantify the impact of reproductive state on biotin status response to a known dietary intake of biotin. METHODS: To achieve this aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27 at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and control (n = 21) women who participated in a 10- to 12-wk feeding study providing 57 MUg of dietary biotin/d as part of a mixed diet. RESULTS: Over the course of the study, pregnant women excreted 69% more (vs. control; P < 0.001) 3 hydroxyisovaleric acid (3-HIA), a metabolite that accumulates during the catabolism of leucine when the activity of biotin-dependent methylcrotonyl coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3 hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA, was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may arise from carnitine inadequacy during gestation. No differences (P > 0.05) were detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between pregnant and control women. Lactating women excreted 76% more (vs. control; P = 0.001) of the biotin catabolite bisnorbiotin, indicating that lactation accelerates biotin turnover and loss. Notably, with respect to control women, lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P = 0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine catabolism and that these metabolites may not be useful indicators of biotin status during lactation. CONCLUSIONS: Overall, these data demonstrate significant alterations in markers of biotin metabolism during pregnancy and lactation and suggest that biotin intakes exceeding current recommendations are needed to meet the demands of these reproductive states. This trial was registered at clinicaltrials.gov as NCT01127022. PMID- 25122651 TI - Fatty Acid Binding Protein 3 Is Involved in n-3 and n-6 PUFA transport in mouse trophoblasts. AB - BACKGROUND: Low placental fatty acid (FA) transport during the embryonic period has been suggested to result in fetal developmental disorders and various adult metabolic diseases, but the molecular mechanism by which FAs are transported through the placental unit remains largely unknown. OBJECTIVE: The aim of this study was to examine the distribution and functional relevance of FA binding protein (FABP), a cellular chaperone of FAs, in the mouse placenta. METHODS: We clarified the localization of FABPs and sought to examine their function in placental FA transport through the phenotypic analysis of Fabp3-knockout mice. RESULTS: Four FABPs (FABP3, FABP4, FABP5, and FABP7) were expressed with spatial heterogeneity in the placenta, and FABP3 was dominantly localized to the trophoblast cells. In placentas from the Fabp3-knockout mice (both sexes), the transport coefficients for linoleic acid (LA) were significantly reduced compared with those from wild-type mice by 25% and 44% at embryonic day (E) 15.5 and E18.5, respectively, whereas those for alpha-linolenic acid (ALA) were reduced by 19% and 17%, respectively. The accumulation of LA (18% and 27% at E15.5 and E18.5) and ALA (16% at E15.5) was also significantly less in the Fabp3-knockout fetuses than in wild-type fetuses. In contrast, transport and accumulation of palmitic acid (PA) were unaffected and glucose uptake significantly increased by 23% in the gene-ablated mice compared with wild-type mice at E18.5. Incorporation of LA (51% and 52% at 1 and 60 min, respectively) and ALA (23% at 60 min), but not PA, was significantly less in FABP3-knockdown BeWo cells than in controls, whereas glucose uptake was significantly upregulated by 51%, 50%, 31%, and 33% at 1, 20, 40, and 60 min, respectively. CONCLUSIONS: Collectively FABP3 regulates n 3 (omega-3) and n-6 (omega-6) polyunsaturated FA transport in trophoblasts and plays a pivotal role in fetal development. PMID- 25122650 TI - Gestational iron deficiency is associated with pica behaviors in adolescents. AB - A relation between pica (the craving and purposive consumption of nonfood items) during pregnancy and anemia is observed frequently. However, few studies related pica behaviors to biomarkers of iron status, and little is known about pica prevalence in U.S. pregnant adolescents. To address this, we undertook a longitudinal study examining iron status and pica behaviors among a group of 158 pregnant adolescents (aged <=18 y). Approximately two-thirds of the participants were African American and 25% were Hispanic. Maternal iron status indicators [hemoglobin, soluble transferrin receptor, serum ferritin (SF), total body iron (TBI), and serum hepcidin] were assessed during pregnancy (18.5-37.3 wk) and at delivery. Pica behavior was assessed up to 3 times across gestation. Among the 158 adolescents, 46% reported engaging in pica behavior. Substances ingested included ice (37%), starches (8%), powders (4%), and soap (3%). During pregnancy, mean SF [geometric mean: 13.6 MUg/L (95% CI: 11.0, 17.0 MUg/L)], TBI (mean +/- SD: 2.5 +/- 4.2 mg/kg), and hepcidin [geometric mean: 19.1 MUg/L (95% CI: 16.3, 22.2 MUg/L)] concentrations were significantly lower (P < 0.05) in the pica group (n = 72) than values observed among the non-pica group [SF, geometric mean: 21.1 MUg/L (95% CI: 18.0, 25.0 MUg/L); TBI, mean +/- SD: 4.3 +/- 3.5 mg/kg; hepcidin, geometric mean: 27.1 MUg/L (95%: 23.1, 32.1 MUg/L); n = 86]. Although additional studies must address the etiology of these relations, this practice should be screened for, given its association with low iron status and because many of the substances ingested may be harmful. This trial was registered at clinicaltrials.gov as NCT01019902. PMID- 25122652 TI - The development of halophyte-based agriculture: past and present. AB - BACKGROUND: Freshwater comprises about a mere 2.5% of total global water, of which approximately two-thirds is locked into glaciers at the polar ice caps and on mountains. In conjunction with this, in many instances irrigation with freshwater causes an increase in soil salinity due to overirrigation of agricultural land, inefficient water use and poor drainage of unsuitable soils. The problem of salinity was recognized a long time ago and, due to the importance of irrigated agriculture, numerous efforts have been devoted towards improving crop species for better utilization of saline soils and water. Irrigating plants with saline water is a challenge for practitioners and researchers throughout the world. SCOPE: Recruiting wild halophytes with economic potential was suggested several decades ago as a way to reduce the damage caused by salinization of soil and water. A range of cultivation systems for the utilization of halophytes have been developed, for the production of biofuel, purification of saline effluent in constructed wetlands, landscaping, cultivation of gourmet vegetables, and more. This review critically analyses past and present halophyte-based production systems in the context of genetics, physiology, agrotechnical issues and product value. There are still difficulties that need to be overcome, such as direct germination in saline conditions or genotype selection. However, more and more research is being directed not only towards determining salt tolerance of halophytes, but also to the improvement of agricultural traits for long-term progress. PMID- 25122653 TI - Resin duct size and density as ecophysiological traits in fire scars of Pseudotsuga menziesii and Larix occidentalis. AB - BACKGROUND AND AIMS: Resin ducts (RDs) are features present in most conifer species as defence structures against pests and pathogens; however, little is known about RD expression in trees following fire injury. This study investigates changes in RD size and density in fire scars of Douglas fir (Pseudotsuga menziesii) and western larch (Larix occidentalis) as a means to evaluate the ecophysiological significance of traumatic resinosis for tree defence and survival. METHODS: Transverse and tangential microsections were prepared for light microscopy and image analysis in order to analyse axial and radial RDs, respectively. Epithelial cells of RDs and fusiform rays associated with radial RDs were also examined. RDs were compared between normal xylem and wound xylem at four different section heights along the fire-injured stem. KEY RESULTS: Following fire injury, P. menziesii axial RDs narrowed by 38-43 % in the first year after injury, and the magnitude of this change increased with stem height. Larix occidentalis axial RDs widened by 46-50 % in the second year after injury. Radial RDs were of equivalent size in P. menziesii, but widened by 162-214 % in L. occidentalis. Fusiform rays were larger following fire injury, by 4-14 % in P. menziesii and by 23-38 % in L. occidentalis. Furthermore, axial RD density increased in both species due to the formation of tangential rows of traumatic RDs, especially in the first and second years after injury. However, radial RD density did not change significantly. CONCLUSIONS: These results highlight traumatic resinosis as a species-specific response. Pseudotsuga menziesii produce RDs of equivalent or reduced size, whereas L. occidentalis produce wider RDs in both the axial and radial duct system, thereby increasing resin biosynthesis and accumulation within the whole tree. Larix occidentalis thus appears to allocate more energy to defence than P. menziesii. PMID- 25122654 TI - Labellar anatomy and secretion in Bulbophyllum Thouars (Orchidaceae: Bulbophyllinae) sect. Racemosae Benth. & Hook. f. AB - BACKGROUND AND AIMS: Floral secretions are common in Bulbophyllum Thouars, and the labella of a number of Asian species are said to produce secretions rich in lipids that act as food rewards for insect pollinators. Although some of these reports are based on simple histochemical tests, a much greater number are anecdotal and, hitherto, neither the ultrastructure of the labellum nor the secretory process has been investigated in detail. Furthermore, sophisticated histochemical approaches have generally not been applied. Here, both the labellar structure and the secretory process are investigated for four species of Asian Bulbophyllum sect. Racemosae Benth. & Hook. f., namely Bulbophyllum careyanum (Hook.) Spreng., B. morphologorum Kraenzl., B. orientale Seidenf. and B. wangkaense Seidenf., and compared with those of unequivocal lipid-secreting orchids. METHODS: Labellar, secretory tissue was investigated using light microscopy, scanning electron microscopy, transmission electron microscopy and histochemistry. KEY RESULTS: The adaxial median longitudinal groove of the labellum contained secretory tissue comprising palisade-like epidermal cells, similar to those of certain lipid-secreting Oncidiinae Benth. However, these cells and their secretions gave positive results mainly for protein and mucilage, and their organelle complement was consistent with that of cells involved in protein and mucilage synthesis. Sub-cuticular accumulation of secretion resulted in cuticular distension and blistering. The sub-epidermal layer of isodiametric parenchyma contained starch and, like the epidermal cells, ultrastructure consistent with mucilage synthesis. Lipids were mainly confined to the cuticle, and hardly any intracellular lipid droplets were observed. CONCLUSIONS: It is proposed that mucilage is produced by dictyosomes present in the palisade-like epidermal cells. Mucilage precursors may also be produced by these same organelles in sub-epidermal cells and are thought to pass along the symplast via plasmodesmata into the adjoining palisade-like secretory cells, which contain abundant arrays of rough endoplasmic reticulum. Here, they become chemically modified and form a protein-rich, mucilaginous secretion that, following vesicle mediated transport across the cytoplasm, traverses the cell wall and accumulates in blisters formed from the distended cuticle. Rupture of these blisters releases the secretion onto the labellar surface. However, in certain species, there is some evidence that the secretion may traverse the cuticle via cuticular pores, and micro-channels may permit the passage of fragrance. Hydrolysis of sub epidermal starch probably generates the carbohydrate and, together with mitochondria, much of the energy required for the secretory process. This anatomical organization resembles that found in certain lipid-secreting, Neotropical species of Bulbophyllum and Oncidiinae, but since the chemical composition of their secretions is different, and these taxa occur on a separate continent and have different insect pollinators, parallelism of floral anatomy is likely. PMID- 25122655 TI - Responses to shading of naturalized and non-naturalized exotic woody species. AB - BACKGROUND AND AIMS: Recent studies have suggested that responses to shading gradients may play an important role in establishment success of exotic plants, but hitherto few studies have tested this. Therefore, a common-garden experiment was conducted using multiple Asian woody plant species that were introduced to Europe >100 years ago in order to test whether naturalized and non-naturalized species differ in their responses to shading. Specifically, a test was carried out to determine whether naturalized exotic woody species maintained better growth under shaded conditions, and whether they expressed greater (morphological and physiological) adaptive plasticity in response to shading, relative to non naturalized species. METHODS: Nineteen naturalized and 19 non-naturalized exotic woody species were grown under five light levels ranging from 100 to 7 % of ambient light. For all plants, growth performance (i.e. biomass), morphological and CO2 assimilation characteristics were measured. For the CO2 assimilation characteristics, CO2 assimilation rate was measured at 1200 MUmol m(-2) s(-1) (i.e. saturated light intensity, A1200), 50 MUmol m(-2) s(-1) (i.e. low light intensity, A50) and 0 MUmol m(-2) s(-1) (A0, i.e. dark respiration). KEY RESULTS: Overall, the naturalized and non-naturalized species did not differ greatly in biomass production and measured morphological and CO2 assimilation characteristics across the light gradient. However, it was found that naturalized species grew taller and reduced total leaf area more than non-naturalized species in response to shading. It was also found that naturalized species were more capable of maintaining a high CO2 assimilation rate at low light intensity (A50) when grown under shading. CONCLUSIONS: The results indicate that there is no clear evidence that the naturalized species possess a superior response to shading over non-naturalized species, at least not at the early stage of their growth. However, the higher CO2 assimilation capacity of the naturalized species under low-light conditions might facilitate early growth and survival, and thereby ultimately favour their initial population establishment over the non naturalized species. PMID- 25122657 TI - Modelling biomechanics of bark patterning in grasstrees. AB - BACKGROUND AND AIMS: Bark patterns are a visually important characteristic of trees, typically attributed to fractures occurring during secondary growth of the trunk and branches. An understanding of bark pattern formation has been hampered by insufficient information regarding the biomechanical properties of bark and the corresponding difficulties in faithfully modelling bark fractures using continuum mechanics. This study focuses on the genus Xanthorrhoea (grasstrees), which have an unusual bark-like structure composed of distinct leaf bases connected by sticky resin. Due to its discrete character, this structure is well suited for computational studies. METHODS: A dynamic computational model of grasstree development was created. The model captures both the phyllotactic pattern of leaf bases during primary growth and the changes in the trunk's width during secondary growth. A biomechanical representation based on a system of masses connected by springs is used for the surface of the trunk, permitting the emergence of fractures during secondary growth to be simulated. The resulting fracture patterns were analysed statistically and compared with images of real trees. KEY RESULTS: The model reproduces key features of grasstree bark patterns, including their variability, spanning elongated and reticulate forms. The patterns produced by the model have the same statistical character as those seen in real trees. CONCLUSIONS: The model was able to support the general hypothesis that the patterns observed in the grasstree bark-like layer may be explained in terms of mechanical fractures driven by secondary growth. Although the generality of the results is limited by the unusual structure of grasstree bark, it supports the hypothesis that bark pattern formation is primarily a biomechanical phenomenon. PMID- 25122656 TI - Contribution of above- and below-ground plant traits to the structure and function of grassland soil microbial communities. AB - BACKGROUND AND AIMS: Abiotic properties of soil are known to be major drivers of the microbial community within it. Our understanding of how soil microbial properties are related to the functional structure and diversity of plant communities, however, is limited and largely restricted to above-ground plant traits, with the role of below-ground traits being poorly understood. This study investigated the relative contributions of soil abiotic properties and plant traits, both above-ground and below-ground, to variations in microbial processes involved in grassland nitrogen turnover. METHODS: In mountain grasslands distributed across three European sites, a correlative approach was used to examine the role of a large range of plant functional traits and soil abiotic factors on microbial variables, including gene abundance of nitrifiers and denitrifiers and their potential activities. KEY RESULTS: Direct effects of soil abiotic parameters were found to have the most significant influence on the microbial groups investigated. Indirect pathways via plant functional traits contributed substantially to explaining the relative abundance of fungi and bacteria and gene abundances of the investigated microbial communities, while they explained little of the variance in microbial activities. Gene abundances of nitrifiers and denitrifiers were most strongly related to below-ground plant traits, suggesting that they were the most relevant traits for explaining variation in community structure and abundances of soil microbes involved in nitrification and denitrification. CONCLUSIONS: The results suggest that consideration of plant traits, and especially below-ground traits, increases our ability to describe variation in the abundances and the functional characteristics of microbial communities in grassland soils. PMID- 25122658 TI - Mitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy. AB - One of the genes involved in Charcot-Marie-Tooth (CMT) disease, an inherited peripheral neuropathy, is GDAP1. In this work, we show that there is a true ortholog of this gene in Drosophila, which we have named Gdap1. By up- and down regulation of Gdap1 in a tissue-specific manner, we show that altering its levels of expression produces changes in mitochondrial size, morphology and distribution, and neuronal and muscular degeneration. Interestingly, muscular degeneration is tissue-autonomous and not dependent on innervation. Metabolic analyses of our experimental genotypes suggest that alterations in oxidative stress are not a primary cause of the neuromuscular degeneration but a long-term consequence of the underlying mitochondrial dysfunction. Our results contribute to a better understanding of the role of mitochondria in CMT disease and pave the way to generate clinically relevant disease models to study the relationship between mitochondrial dynamics and peripheral neurodegeneration. PMID- 25122659 TI - Absence of ALOX5 gene prevents stress-induced memory deficits, synaptic dysfunction and tauopathy in a mouse model of Alzheimer's disease. AB - Although the initial events of Alzheimer's disease (AD) are still not known, it is clear that the disease in its sporadic form results from the combination of genetic and environmental risk factors. Among the latter, behavioral stress has been increasingly recognized as an important factor in the propagation of AD. However, the mechanisms underlying this modulation remain to be fully investigated. Since stress up-regulates the ALOX5 gene product, 5-lipoxygenase (5LO), herein we investigated its role in modulating stress-dependent development of the AD phenotype. To reach this goal, triple transgenic (3xTg) mice and 3xTg genetically deficient for 5LO were investigated after undergoing a restraint/isolation paradigm. In the present paper, we found that 28 days of restraint/isolation stress worsened tau phosphorylation and solubility, increased glycogen synthase kinase 3beta activity, compromised long-term potentiation and impaired fear-conditioned memory recall in 3xTg animals, but not in 3xTg animals lacking 5LO (3xTg/5LO-/-). These results highlight the novel functional role that the ALOX5 gene plays in the development of the biochemical, electrophysiological and behavioral sequelae of stress in the AD context. They provide critical support that this gene and its expressed protein are viable therapeutic targets to prevent the onset or delay the progression of AD in individuals exposed to this risk factor. PMID- 25122660 TI - Synergic prodegradative activity of Bicalutamide and trehalose on the mutant androgen receptor responsible for spinal and bulbar muscular atrophy. AB - Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease due to a CAG triplet-repeat expansion in the androgen receptor (AR) gene, which is translated into an elongated polyglutamine (polyQ) tract in AR protein (ARpolyQ). ARpolyQ toxicity is activated by the AR ligand testosterone (or dihydrotestosterone), and the polyQ triggers ARpolyQ misfolding and aggregation in spinal cord motoneurons and muscle cells. In motoneurons, testosterone triggers nuclear toxicity by inducing AR nuclear translocation. Thus, (i) prevention of ARpolyQ nuclear localization, combined with (ii) an increased ARpolyQ cytoplasmic clearance, should reduce its detrimental activity. Using the antiandrogen Bicalutamide (Casodex((r))), which slows down AR activation and nuclear translocation, and the disaccharide trehalose, an autophagy activator, we found that, in motoneurons, the two compounds together reduced ARpolyQ insoluble forms with higher efficiency than that obtained with single treatments. The ARpolyQ clearance was mediated by trehalose-induced autophagy combined with the longer cytoplasmic retention of ARpolyQ bound to Bicalutamide. This allows an increased recognition of misfolded species by the autophagic system prior to their migration into the nucleus. Interestingly, the combinatory use of trehalose and Bicalutamide was also efficient in the removal of insoluble species of AR with a very long polyQ (Q112) tract, which typically aggregates into the cell nuclei. Collectively, these data suggest that the combinatory use of Bicalutamide and trehalose is a novel approach to facilitate ARpolyQ clearance that has to be tested in other cell types target of SBMA (i.e. muscle cells) and in vivo in animal models of SBMA. PMID- 25122661 TI - TDP-43 loss of cellular function through aggregation requires additional structural determinants beyond its C-terminal Q/N prion-like domain. AB - TDP-43 aggregates are the neurohistological landmark of diseases like amyotrophic lateral sclerosis and frontotemporal dementia. Their role in the pathogenesis of these conditions is not yet clear mainly due to the lack of proper models of aggregation that may allow the study of the mechanism of formation, their interactions with other cellular components and their effect on the cell metabolism. In this work, we have used tandem repeats of the prion like Q/N-rich region of TAR DNA-binding protein (TDP-43) fused to additional TDP-43 protein sequences to trigger aggregate formation in neuronal and non-neuronal cell lines. At the functional level, these aggregates are able to sequester endogenous TDP-43 depleting its nuclear levels and inducing loss of function at the pre-mRNA splicing level. No apparent direct cellular toxicity of the aggregates seems to be present beyond the lack of functional TDP-43. To our knowledge, this is the only system that achieves full functional TDP 43 depletion with effects similar to RNAi depletion or gene deletion. As a result, this model will prove useful to investigate the loss-of-function effects mediated by TDP-43 aggregation within cells without affecting the expression of the endogenous gene. We have identified the N-terminus sequence of TDP-43 as the domain that enhances its interaction with the aggregates and its insolubilization. These data show for the first time that cellular TDP-43 aggregation can lead to total loss of function and to defective splicing of TDP-43-dependent splicing events in endogenous genes. PMID- 25122664 TI - Practice patterns and trends in the use of medical therapy in patients undergoing percutaneous coronary intervention in Ontario. AB - BACKGROUND: Clinical guidelines emphasize medical therapy as the initial approach to the management of patients with stable coronary artery disease (CAD). However, the extent to which medical therapy is applied before and after percutaneous coronary intervention (PCI) in contemporary clinical practice is uncertain. We evaluated medication use for patients with stable CAD undergoing PCI, and assessed whether the COURAGE study altered medication use in the Canadian healthcare system. METHODS AND RESULTS: A population-based cohort of 23 680 older patients >65 years old) with stable CAD undergoing PCI in Ontario between 2003 and 2010 was assembled. Optimal medical therapy (OMT) was defined as prescription for a beta-blocker, statin, and either angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in the 90 days before PCI, and the same medications plus thienopyridine 90 days following PCI. Prior to PCI, 8023 (33.9%) patients were receiving OMT, 11 891 (50.2%) were on suboptimal therapy, and 3766 (15.9%) were not prescribed any medications of interest. There was significant improvement in medical therapy following PCI (OMT: 11 149 [47.1%], suboptimal therapy: 11 591 [48.9%], and none: 940 [4.0%], P<0.001). Utilization rate of OMT reduced significantly after the publication of COURAGE (34.9% before versus 32.8% after, P<0.001). Similarly, the rate of OMT following PCI was lower in the period after publication of COURAGE (47.3% before versus 46.9% after, P<0.001). CONCLUSIONS: OMT was prescribed in about 1 in 3 patients prior to PCI and less than half after PCI. In contrast to the anticipated impact of COURAGE, we found lower rates of medication use in PCI patients after its publication. PMID- 25122662 TI - Genomic analysis of fibrolamellar hepatocellular carcinoma. AB - Pediatric tumors are relatively infrequent, but are often associated with significant lethality and lifelong morbidity. A major goal of pediatric cancer research has been to identify key drivers of tumorigenesis to eventually develop targeted therapies to enhance cure rate and minimize acute and long-term toxic effects. Here, we used genomic approaches to identify biomarkers and candidate drivers for fibrolamellar hepatocellular carcinoma (FL-HCC), a very rare subtype of pediatric liver cancer for which limited therapeutic options exist. In-depth genomic analyses of one tumor followed by immunohistochemistry validation on seven other tumors showed expression of neuroendocrine markers in FL-HCC. DNA and RNA sequencing data further showed that common cancer pathways are not visibly altered in FL-HCC but identified two novel structural variants, both resulting in fusion transcripts. The first, a 400 kb deletion, results in a DNAJB1-PRKCA fusion transcript, which leads to increased cAMP-dependent protein kinase (PKA) activity in the index tumor case and other FL-HCC cases compared with normal liver. This PKA fusion protein is oncogenic in HCC cells. The second gene fusion event, a translocation between the CLPTM1L and GLIS3 genes, generates a transcript whose product also promotes cancer phenotypes in HCC cell lines. These experiments further highlight the tumorigenic role of gene fusions in the etiology of pediatric solid tumors and identify both candidate biomarkers and possible therapeutic targets for this lethal pediatric disease. PMID- 25122663 TI - Plasma phospholipid fatty acid biomarkers of dietary fat quality and endogenous metabolism predict coronary heart disease risk: a nested case-control study within the Women's Health Initiative observational study. AB - BACKGROUND: Although the relationship between dietary fat quality and coronary heart disease (CHD) risk has been evaluated, typically using diet questionnaires, results are inconsistent and data in postmenopausal women are limited. Plasma phospholipid fatty acid (PL-FA) profiles, reflecting dietary intake and endogenous FA metabolism, may better predict diet-CHD risk. METHODS AND RESULTS: Using a nested case-control design, we assessed the association between plasma PL FA profiles and CHD risk in 2448 postmenopausal women (1224 cases with confirmed CHD and 1224 controls matched for age, enrollment date, race/ethnicity, and absence of CHD at baseline and after 4.5 years of follow-up) participating in the Women's Health Initiative observational study. PL-FA profile was measured using gas chromatography. Product/precursor ratios were used to estimate stearoyl-CoA desaturase (16:1n-7/16:0, 18:1n-9/18:0), Delta6-desaturase (20:3n-6/18:2n-6), and Delta5-desaturase (20:4n-6/20:3n-6) activities, indicators of endogenous FA metabolism. Multivariate conditional logistic regression was used to obtain odds ratios (95% CIs) for CHD risk. While no associations were observed for the predominant PL fatty acid (16:0, 18:0, 18:1n-9, and 18:2n-6), plasma PL-saturated fatty acid (1.20 [1.08 to 1.32]) and endogenously synthesized PL omega6 fatty acids (20:3n-6; 3.22 [1.95 to 5.32]), 22:5n-6; 1.63 [1.20 to 2.23]) and Delta6 desaturase (1.25 [1.11 to 1.41]) were positively associated with CHD risk. PL omega3 fatty acids (20:5n-3; 0.73 [0.58 to 0.93], 22:5n-3; 0.56 [0.33 to 0.94], 22:6n-3; 0.56 [0.39 to 0.80]), 18:1n-7 (0.54 [0.29 to 0.99]), and Delta5 desaturase (0.78 [0.70 to 0.88]) were inversely associated with CHD risk. Results support current guidelines regarding regular fish consumption. Additional findings include associations between endogenously synthesized fatty acids and CHD risk, which were partly explained by changes in Delta6-desaturase and Delta5 desaturase indexes, suggesting that in vivo metabolism may also play an important role in predicting CHD risk in this cohort of postmenopausal women. CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov, Unique identifier: NCT01864122. PMID- 25122665 TI - Choosing wisely for syncope: low-value carotid ultrasound use. AB - BACKGROUND: The United States spends more than $750 billion annually on tests and procedures that do not benefit patients. Although there is no physiological indication for carotid ultrasound in "simple" syncope in the absence of focal neurological signs or symptoms suggestive of stroke, there is concern that this practice remains common for routine syncope workups. METHODS AND RESULTS: We used a 5% random-sample Medicare claims database to evaluate large-scale national trends in utilization of low-value carotid ultrasound imaging for simple syncope. We found that 16.5% of all Medicare beneficiaries with simple syncope underwent carotid imaging and 6.5% of all carotid ultrasounds ordered in 2009 were for this low-value indication. These findings were complemented by a manual chart review of 313 patients at a large academic medical center who underwent carotid ultrasound for simple syncope over a 5-year period. For the 48 (15.4%) of 313 patients with stenosis >=50%, carotid ultrasound did not yield a causal diagnosis. Only 2% of the 313 patients imaged experienced a change in medications after a positive study, and <1% of patients underwent a carotid revascularization procedure. CONCLUSIONS: These data suggest that carotid ultrasound for patients with uncomplicated syncope are still commonly ordered and may be an easy target for institutions striving to curtail low-value care. PMID- 25122666 TI - Association of lower extremity performance with cardiovascular and all-cause mortality in patients with peripheral artery disease: a systematic review and meta-analysis. AB - BACKGROUND: Peripheral artery disease (PAD) is associated with impaired mobility and a high rate of mortality. The aim of this systematic review was to investigate whether reduced lower extremity performance was associated with an increased incidence of cardiovascular and all-cause mortality in people with PAD. METHODS AND RESULTS: A systematic search of the MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane Library databases was conducted. Studies assessing the association between measures of lower extremity performance and cardiovascular or all-cause mortality in PAD patients were included. A meta-analysis was conducted combining data from commonly assessed performance tests. The 10 identified studies assessed lower extremity performance by strength tests, treadmill walking performance, 6-minute walk, walking velocity, and walking impairment questionnaire (WIQ). A meta-analysis revealed that shorter maximum walking distance was associated with increased 5-year cardiovascular (unadjusted RR=2.54, 95% CI 1.86 to 3.47, P<10(-5), n=1577, fixed effects) and all-cause mortality (unadjusted RR=2.23 95% CI 1.85 to 2.69, P<10(-5), n=1710, fixed effects). Slower 4-metre walking velocity, a lower WIQ stair-climbing score, and poor hip extension, knee flexion, and plantar flexion strength were also associated with increased mortality. No significant associations were found for hip flexion strength, WIQ distance score, or WIQ speed score with mortality. CONCLUSIONS: A number of lower extremity performance measures are prognostic markers for mortality in PAD and may be useful clinical tools for identifying patients at higher risk of death. Further studies are needed to determine whether interventions that improve measures of lower extremity performance reduce mortality. PMID- 25122667 TI - Polymorphism identification and improved genome annotation of Brassica rapa through Deep RNA sequencing. AB - The mapping and functional analysis of quantitative traits in Brassica rapa can be greatly improved with the availability of physically positioned, gene-based genetic markers and accurate genome annotation. In this study, deep transcriptome RNA sequencing (RNA-Seq) of Brassica rapa was undertaken with two objectives: SNP detection and improved transcriptome annotation. We performed SNP detection on two varieties that are parents of a mapping population to aid in development of a marker system for this population and subsequent development of high-resolution genetic map. An improved Brassica rapa transcriptome was constructed to detect novel transcripts and to improve the current genome annotation. This is useful for accurate mRNA abundance and detection of expression QTL (eQTLs) in mapping populations. Deep RNA-Seq of two Brassica rapa genotypes-R500 (var. trilocularis, Yellow Sarson) and IMB211 (a rapid cycling variety)-using eight different tissues (root, internode, leaf, petiole, apical meristem, floral meristem, silique, and seedling) grown across three different environments (growth chamber, greenhouse and field) and under two different treatments (simulated sun and simulated shade) generated 2.3 billion high-quality Illumina reads. A total of 330,995 SNPs were identified in transcribed regions between the two genotypes with an average frequency of one SNP in every 200 bases. The deep RNA-Seq reassembled Brassica rapa transcriptome identified 44,239 protein-coding genes. Compared with current gene models of B. rapa, we detected 3537 novel transcripts, 23,754 gene models had structural modifications, and 3655 annotated proteins changed. Gaps in the current genome assembly of B. rapa are highlighted by our identification of 780 unmapped transcripts. All the SNPs, annotations, and predicted transcripts can be viewed at http://phytonetworks.ucdavis.edu/. PMID- 25122669 TI - Evidence of hermaphroditism and sex ratio distortion in the fungal feeding nematode Bursaphelenchus okinawaensis. AB - Nematodes have many different reproductive strategies along with their divergent life histories; the ability of hermaphrodite to self- and cross-fertilize is useful for genetic manipulation. Here, we demonstrate the hermaphroditism of the fungal feeding nematode Bursaphelenchus okinawaensis, which was formerly described as a parthenogenetic nematode, and we show its other unique sexual characteristics. To determine that it is hermaphroditic, we performed the following experiments: observation of the pronuclear and chromosome behavior during oogenesis and early embryogenesis; observation of spermatogenesis during the fourth larval stage; investigation of sperm utilization; and investigation of phenotypic segregation after cross-mating using a chemically induced visible mutant. We then investigated the mating preferences and spermatid size difference between males and hermaphrodites. B. okinawaensis males successfully mated only with sperm-depleted old hermaphrodites, and the spermatid sizes of males were almost the same as those of hermaphrodites. Moreover, the sex ratio of cross fertilized progeny was highly skewed toward hermaphrodites. B. okinawaensis is phylogenetically distant from established model nematodes such as C. elegans and is more closely related to some economically relevant parasitic nematodes. This newly discovered hermaphroditic nematode has great potential for evolutionary and parasitological research. PMID- 25122668 TI - Genome-wide linkage disequilibrium in nine-spined stickleback populations. AB - Variation in the extent and magnitude of genome-wide linkage disequilibrium (LD) among populations residing in different habitats has seldom been studied in wild vertebrates. We used a total of 109 microsatellite markers to quantify the level and patterns of genome-wide LD in 13 Fennoscandian nine-spined stickleback (Pungitius pungitius) populations from four (viz. marine, lake, pond, and river) different habitat types. In general, high magnitude (D' > 0.5) of LD was found both in freshwater and marine populations, and the magnitude of LD was significantly greater in inland freshwater than in marine populations. Interestingly, three coastal freshwater populations located in close geographic proximity to the marine populations exhibited similar LD patterns and genetic diversity as their marine neighbors. The greater levels of LD in inland freshwater compared with marine and costal freshwater populations can be explained in terms of their contrasting demographic histories: founder events, long-term isolation, small effective sizes, and population bottlenecks are factors likely to have contributed to the high levels of LD in the inland freshwater populations. In general, these findings shed new light on the patterns and extent of variation in genome-wide LD, as well as the ecological and evolutionary factors driving them. PMID- 25122670 TI - Distinct and predictive histone lysine acetylation patterns at promoters, enhancers, and gene bodies. AB - In eukaryotic cells, histone lysines are frequently acetylated. However, unlike modifications such as methylations, histone acetylation modifications are often considered redundant. As such, the functional roles of distinct histone acetylations are largely unexplored. We previously developed an algorithm RFECS to discover the most informative modifications associated with the classification or prediction of mammalian enhancers. Here, we used this tool to identify the modifications most predictive of promoters, enhancers, and gene bodies. Unexpectedly, we found that histone acetylation alone performs well in distinguishing these unique genomic regions. Further, we found the association of characteristic acetylation patterns with genic regions and association of chromatin state with splicing. Taken together, our work underscores the diverse functional roles of histone acetylation in gene regulation and provides several testable hypotheses to dissect these roles. PMID- 25122672 TI - The health effects of employment. PMID- 25122671 TI - Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. AB - BACKGROUND: Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. PATIENTS AND METHODS: Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. RESULTS: Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09 0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16-0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6-2.2, P = 0.833). CONCLUSIONS: Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified PFS threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care. Encouraging median OS and safety data from this well-controlled and appropriately designed randomized trial indicate a positive benefit-risk ratio. Further development of masitinib in imatinib-resistant/intolerant patients with advanced GIST is warranted. PMID- 25122674 TI - Clovis at the end of the world. PMID- 25122675 TI - Plasmonic nanoparticle scattering for color holograms. AB - This work presents an original approach to create holograms based on the optical scattering of plasmonic nanoparticles. By analogy to the diffraction produced by the scattering of atoms in X-ray crystallography, we show that plasmonic nanoparticles can produce a wave-front reconstruction when they are sampled on a diffractive plane. By applying this method, all of the scattering characteristics of the nanoparticles are transferred to the reconstructed field. Hence, we demonstrate that a narrow-band reconstruction can be achieved for direct white light illumination on an array of plasmonic nanoparticles. Furthermore, multicolor capabilities are shown with minimal cross-talk by multiplexing different plasmonic nanoparticles at subwavelength distances. The holograms were fabricated from a single subwavelength thin film of silver and demonstrate that the total amount of binary information stored in the plane can exceed the limits of diffraction and that this wavelength modulation can be detected optically in the far field. PMID- 25122676 TI - Pharmacological chaperones in the age of proteomic pathology. PMID- 25122673 TI - Calcineurin determines toxic versus beneficial responses to alpha-synuclein. AB - Calcineurin (CN) is a highly conserved Ca(2+)-calmodulin (CaM)-dependent phosphatase that senses Ca(2+) concentrations and transduces that information into cellular responses. Ca(2+) homeostasis is disrupted by alpha-synuclein (alpha-syn), a small lipid binding protein whose misfolding and accumulation is a pathological hallmark of several neurodegenerative diseases. We report that alpha syn, from yeast to neurons, leads to sustained highly elevated levels of cytoplasmic Ca(2+), thereby activating a CaM-CN cascade that engages substrates that result in toxicity. Surprisingly, complete inhibition of CN also results in toxicity. Limiting the availability of CaM shifts CN's spectrum of substrates toward protective pathways. Modulating CN or CN's substrates with highly selective genetic and pharmacological tools (FK506) does the same. FK506 crosses the blood brain barrier, is well tolerated in humans, and is active in neurons and glia. Thus, a tunable response to CN, which has been conserved for a billion years, can be targeted to rebalance the phosphatase's activities from toxic toward beneficial substrates. These findings have immediate therapeutic implications for synucleinopathies. PMID- 25122678 TI - Reconsidering the phylogenetic utility of miRNA in animals. PMID- 25122677 TI - Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity. AB - Graves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFNalpha, a key cytokine secreted during viral infections, and overlapped them with known GD associated SNPs. We mapped an open chromatin region overlapping two adjacent GD associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261 site. Repression by PLZF depended on the rs12101261 disease susceptibility allele and was increased by IFNalpha. Intrathymic TSHR expression was decreased in individuals homozygous for the rs12101261 disease-associated genotype compared with carriers of the disease-protective allele. Our studies discovered a genetic epigenetic interaction involving a noncoding SNP in the TSHR gene that regulates thymic TSHR gene expression and facilitates escape of TSHR-reactive T cells from central tolerance, triggering GD. PMID- 25122680 TI - Intraoperative cell-cycle analysis to guide brain tumor removal. PMID- 25122679 TI - Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy. AB - Autophagy is the principal catabolic prosurvival pathway during nutritional starvation. However, excessive autophagy could be cytotoxic, contributing to cell death, but its mechanism remains elusive. Arginine starvation has emerged as a potential therapy for several types of cancers, owing to their tumor-selective deficiency of the arginine metabolism. We demonstrated here that arginine depletion by arginine deiminase induces a cytotoxic autophagy in argininosuccinate synthetase (ASS1)-deficient prostate cancer cells. Advanced microscopic analyses of arginine-deprived dying cells revealed a novel phenotype with giant autophagosome formation, nucleus membrane rupture, and histone associated DNA leakage encaptured by autophagosomes, which we shall refer to as chromatin autophagy, or chromatophagy. In addition, nuclear inner membrane (lamin A/C) underwent localized rearrangement and outer membrane (NUP98) partially fused with autophagosome membrane. Further analysis showed that prolonged arginine depletion impaired mitochondrial oxidative phosphorylation function and depolarized mitochondrial membrane potential. Thus, reactive oxygen species (ROS) production significantly increased in both cytosolic and mitochondrial fractions, presumably leading to DNA damage accumulation. Addition of ROS scavenger N-acetyl cysteine or knockdown of ATG5 or BECLIN1 attenuated the chromatophagy phenotype. Our data uncover an atypical autophagy-related death pathway and suggest that mitochondrial damage is central to linking arginine starvation and chromatophagy in two distinct cellular compartments. PMID- 25122681 TI - A sequence-specific transcription activator motif and powerful synthetic variants that bind Mediator using a fuzzy protein interface. AB - Although many transcription activators contact the same set of coactivator complexes, the mechanism and specificity of these interactions have been unclear. For example, do intrinsically disordered transcription activation domains (ADs) use sequence-specific motifs, or do ADs of seemingly different sequence have common properties that encode activation function? We find that the central activation domain (cAD) of the yeast activator Gcn4 functions through a short, conserved sequence-specific motif. Optimizing the residues surrounding this short motif by inserting additional hydrophobic residues creates very powerful ADs that bind the Mediator subunit Gal11/Med15 with high affinity via a "fuzzy" protein interface. In contrast to Gcn4, the activity of these synthetic ADs is not strongly dependent on any one residue of the AD, and this redundancy is similar to that of some natural ADs in which few if any sequence-specific residues have been identified. The additional hydrophobic residues in the synthetic ADs likely allow multiple faces of the AD helix to interact with the Gal11 activator-binding domain, effectively forming a fuzzier interface than that of the wild-type cAD. PMID- 25122683 TI - No evidence for sample contamination or diet offset for pre-Columbian chicken dates from El Arenal. PMID- 25122682 TI - Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats. AB - Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence. PMID- 25122685 TI - Statistical flaws undermine pre-Columbian chicken debate. PMID- 25122684 TI - No evidence against Polynesian dispersal of chickens to pre-Columbian South America. PMID- 25122686 TI - A Site-Specific Integrated Col2.3GFP Reporter Identifies Osteoblasts Within Mineralized Tissue Formed In Vivo by Human Embryonic Stem Cells. AB - The use of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) for study and treatment of bone diseases or traumatic bone injuries requires efficient protocols to differentiate hESCs/iPSCs into cells with osteogenic potential and the ability to isolate differentiated osteoblasts for analysis. We have used zinc finger nuclease technology to deliver a construct containing the Col2.3 promoter driving GFPemerald to the AAVS1 site (referred to as a "safe harbor" site), in human embryonic stem cells (H9Zn2.3GFP), with the goal of marking the cells that have become differentiated osteoblasts. In teratomas formed using these cells, we identified green fluorescent protein (GFP) positive cells specifically associated with in vivo bone formation. We also differentiated the cells into a mesenchymal stem cell population with osteogenic potential and implanted them into a mouse calvarial defect model. We observed GFP positive cells associated with alizarin complexone-labeled newly formed bone surfaces. The cells were alkaline phosphatase-positive, and immunohistochemistry with human specific bone sialoprotein (BSP) antibody indicates that the GFP positive cells are also associated with the human BSP-containing matrix, demonstrating that the Col2.3GFP construct marks cells in the osteoblast lineage. Single-cell cloning generated a 100% Col2.3GFP-positive cell population, as demonstrated by fluorescence in situ hybridization using a GFP probe. The karyotype was normal, and pluripotency was demonstrated by Tra1-60 immunostaining, pluripotent low density reverse transcription-polymerase chain reaction array and embryoid body formation. These cells will be useful to develop optimal osteogenic differentiation protocols and to isolate osteoblasts from normal and diseased iPSCs for analysis. PMID- 25122687 TI - Are all cancer stem cells created equal? AB - Numerous solid malignancies have been reported to contain cancer stem cells (CSCs). Distinct functional characteristics have been attributed to CSCs, and thus it is widely believed that these unique cells may have genetic and phenotypic homogeneity. Recent exciting but limited evidence, however, contradicts this tenet and supports the intriguing concept of genetic and phenotypic diversity in the CSC population. We propose that CSC heterogeneity at the inter- and intrapatient levels may be due to the cell of origin, to environmental cues, and/or to human papillomavirus infection. Additional insight into CSC heterogeneity is needed to identify actionable targets for optimal eradication of the diverse CSC subpopulations within a tumor. PMID- 25122688 TI - Longitudinal Analysis of DNA Methylation in CD34+ Hematopoietic Progenitors in Myelodysplastic Syndrome. AB - Myelodysplastic syndrome (MDS) is a disorder of hematopoietic stem cells (HSCs) that is often treated with DNA methyltransferase 1 (DNMT1) inhibitors (5 azacytidine [AZA], 5-aza-2'-deoxycytidine), suggesting a role for DNA methylation in disease progression. How DNMT inhibition retards disease progression and how DNA methylation contributes to MDS remain unclear. We analyzed global DNA methylation in purified CD34+ hematopoietic progenitors from MDS patients undergoing multiple rounds of AZA treatment. Differential methylation between MDS phenotypes was observed primarily at developmental regulators not expressed within the hematopoietic compartment and was distinct from that observed between healthy hematopoietic cell types. After AZA treatment, we observed only limited DNA demethylation at sites that varied between patients. This suggests that a subset of the stem cell population is resistant to AZA and provides a basis for disease relapse. Using gene expression data from patient samples and an in vitro AZA treatment study, we identified differentially methylated genes that can be activated following treatment and that remain silent in the CD34+ stem cell compartment of high-risk MDS patients. Haploinsufficiency in mice of one of these genes (NR4A2) has been shown to lead to excessive HSC proliferation, and our data suggest that suppression of NR4A2 by DNA methylation may be involved in MDS progression. PMID- 25122692 TI - Type of homogenization and fat loss during continuous infusion of human milk. AB - BACKGROUND: Substantial fat loss may occur during continuous feeding of human milk (HM). A decrease of fat loss has been described following homogenization. Well-established methods of homogenization of HM for routine use in the neonatal intensive care unit (NICU) would be desirable. OBJECTIVE: We compared the loss of fat based on the use of 3 different methods for homogenizing thawed HM during continuous feeding. METHODS: Sixteen frozen donor HM samples were thawed, homogenized with ultrasound and separated into 3 aliquots ("baseline agitation," "hourly agitation," and "ultrasound"), and then frozen for 48 hours. Aliquots were thawed again and a baseline agitation was applied. Subsequently, aliquots baseline agitation and hourly agitation were drawn into a syringe, while ultrasound was applied to aliquot ultrasound before it was drawn into a syringe. The syringes were loaded into a pump (2 mL/h; 4 hours). At hourly intervals the hourly agitation infusion was stopped, the syringe was disconnected and gently shaken. During infusion, samples from the 3 groups were collected hourly for analysis of fat and caloric content. RESULTS: The 3 groups of homogenization showed similar fat content at the beginning of the infusion. For fat, mean (SD) hourly changes of -0.03 (0.01), -0.09 (0.01), and -0.09 (0.01) g/dL were observed for the hourly agitation, baseline agitation, and ultrasound groups, respectively. The decrease was smaller for the hourly agitation group (P < .001). CONCLUSION: When thawed HM is continuously infused, a smaller fat loss is observed when syringes are agitated hourly versus when ultrasound or a baseline homogenization is used. PMID- 25122691 TI - Concise review: dedifferentiation meets cancer development: proof of concept for epigenetic cancer. AB - The technology for generation of induced pluripotent stem cells (iPSCs) has made significant contributions to various scientific fields, and the field of cancer biology is no exception. Although cancer is generally believed to develop through accumulation of multiple genetic mutations, there is increasing evidence that cancer cells also acquire epigenetic abnormalities during development, maintenance, and progression. Because the epigenetic status of somatic cells changes dynamically through reprogramming, iPSC technology can be utilized to actively and globally alter the epigenetic status of differentiated cells. Using this technology, a recent study has revealed that some types of cancer can develop mainly through disruption of the epigenetic status triggered by dedifferentiation. In this paper, we outline the reprograming process and the epigenetic mechanism associated with the maintenance or conversion of cell identity. We then describe several observations suggesting that dedifferentiation can play an important role in cancer development. Finally, we introduce the system responsible for in vivo reprogramming to demonstrate the involvement of dedifferentiation-driven epigenetic disruption in cancer development, and propose that particular types of cancer can develop predominantly through epigenetic alterations. PMID- 25122690 TI - Cost-effective master cell bank validation of multiple clinical-grade human pluripotent stem cell lines from a single donor. AB - Standardization guidelines for human pluripotent stem cells are still very broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan. The requirements for validation of human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) in general follow the regulations for other clinically compliant biologics already in place but without addressing key differences between cell types or final products. In order to realize the full potential of stem cell therapy, validation criteria, methodology, and, most importantly, strategy, should address the shortfalls and efficiency of current approaches; without this, hESC- and, especially, iPSC-based therapy will not be able to compete with other technologies in a cost-efficient way. We addressed the protocols for testing cell lines for human viral pathogens and propose a novel strategy that would significantly reduce costs. It is highly unlikely that the multiple cell lines derived in parallel from a tissue sample taken from one donor would have different profiles of endogenous viral pathogens; we therefore argue that samples from the Master Cell Banks of sibling lines could be safely pooled for validation. We illustrate this approach with tiered validation of two sibling clinical-grade hESC lines, KCL033 and KCL034 (stage 1, sterility; stage 2, specific human pathogens; and stage 3, nonspecific human pathogens). The results of all tests were negative. This cost-effective strategy could also be applied for validation of Master Cell Banks of multiple clinical-grade iPSC lines derived from a single donor. PMID- 25122689 TI - Different culture conditions modulate the immunological properties of adipose stem cells. AB - The potential of human adipose stem cells (ASCs) for regenerative medicine has received recognition owing to their ease of isolation and their multilineage differentiation capacity. Additionally, low immunogenicity and immunosuppressive properties make them a relevant cell source when considering immunomodulation therapies and allogeneic stem cell treatments. In the current study, immunogenicity and immunosuppression of ASCs were determined through mixed lymphocyte reactions. The immunogenic response was analyzed after cell isolation and expansion in fetal bovine serum (FBS), human serum (HS)-supplemented medium, and xeno-free and serum-free (XF/SF) conditions. Additionally, the immunophenotype and the secretion of CXC chemokine ligand 8 (CXCL8), CXCL9, CXCL10, C-C chemokine ligand 2 (CCL2), CCL5, interleukin 2 (IL-2), IL-4, IL-6, IL 10, IL-17A, tumor necrosis factor-alpha, interferon-gamma, transforming growth factor-beta1, indoleamine 2,3-deoxygenase, Galectin-1, and Galectin-3 were analyzed. The results showed that ASCs were weakly immunogenic when expanded in any of the three conditions. The significantly strongest suppression was observed with cells expanded in FBS conditions, whereas higher ASC numbers were required to display suppression in HS or XF/SF conditions. In addition, statistically significant differences in protein secretion were observed between direct versus indirect cocultures and between different culture conditions. The characteristic immunophenotype of ASCs was maintained in all conditions. However, in XF/SF conditions, a significantly lower expression of CD54 (intercellular adhesion molecule 1) and a higher expression of CD45 (lymphocyte common antigen) was observed at a low passage number. Although culture conditions have an effect on the immunogenicity, immunosuppression, and protein secretion profile of ASCs, our findings demonstrated that ASCs have low immunogenicity and promising immunosuppressive potential whether cultured in FBS, HS, or XF/SF conditions. PMID- 25122693 TI - Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study. AB - BACKGROUND: In T3 rectal cancer (RC), preoperative chemoradiotherapy [5 fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes. PATIENTS AND METHODS: This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5 FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate. RESULTS: Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B). CONCLUSION: Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189. PMID- 25122694 TI - Second-line chemotherapy in advanced biliary cancer: the present now will later be past. PMID- 25122695 TI - Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. PMID- 25122698 TI - SILARS: an effective stable isotope labeling with ammonium nitrate-15N in rice seedlings for quantitative proteomic analysis. PMID- 25122699 TI - A novel single-nucleotide mutation in a CLAVATA3 gene homolog controls a multilocular silique trait in Brassica rapa L. PMID- 25122696 TI - Combinatorial complexity in a transcriptionally centered signaling hub in Arabidopsis. AB - A subfamily of four Phytochrome (phy)-Interacting bHLH transcription Factors (PIFs) collectively promote skotomorphogenic development in dark-grown seedlings. This activity is reversed upon exposure to light, by photoactivated phy molecules that induce degradation of the PIFs, thereby triggering the transcriptional changes that drive a transition to photomorphogenesis. The PIFs function both redundantly and partially differentially at the morphogenic level in this process. To identify the direct targets of PIF transcriptional regulation genome wide, we analyzed the DNA-binding sites for all four PIFs by ChIP-seq analysis, and defined the genes transcriptionally regulated by each PIF, using RNA-seq analysis of pif mutants. Despite the absence of detectable differences in DNA binding-motif recognition between the PIFs, the data show a spectrum of regulatory patterns, ranging from single PIF dominance to equal contributions by all four. Similarly, a broad array of promoter architectures was found, ranging from single PIF-binding sites, containing single sequence motifs, through multiple PIF-binding sites, each containing one or more motifs, with each site occupied preferentially by one to multiple PIFs. Quantitative analysis of the promoter occupancy and expression level induced by each PIF revealed an intriguing pattern. Although there is no robust correlation broadly across the target-gene population, examination of individual genes that are shared targets of multiple PIFs shows a gradation in correlation from strongly positive, through uncorrelated, to negative. This finding suggests a dual-layered mechanism of transcriptional regulation, comprising both a continuum of binding-site occupancy by each PIF and a superimposed layer of local regulation that acts differentially on each PIF, to modulate its intrinsic transcriptional activation capacity at each site, in a quantitative pattern that varies between the individual PIFs from gene to gene. These findings provide a framework for probing the mechanisms by which transcription factors with overlapping direct-target genes integrate and selectively transduce signals to their target networks. PMID- 25122697 TI - MADS-box transcription factor AGL21 regulates lateral root development and responds to multiple external and physiological signals. AB - Plant root system morphology is dramatically influenced by various environmental cues. The adaptation of root system architecture to environmental constraints, which mostly depends on the formation and growth of lateral roots, is an important agronomic trait. Lateral root development is regulated by the external signals coordinating closely with intrinsic signaling pathways. MADS-box transcription factors are known key regulators of the transition to flowering and flower development. However, their functions in root development are still poorly understood. Here we report that AGL21, an AGL17-clade MADS-box gene, plays a crucial role in lateral root development. AGL21 was highly expressed in root, particularly in the root central cylinder and lateral root primordia. AGL21 overexpression plants produced more and longer lateral roots while agl21 mutants showed impaired lateral root development, especially under nitrogen-deficient conditions. AGL21 was induced by many plant hormones and environmental stresses, suggesting a function of this gene in root system plasticity in response to various signals. Furthermore, AGL21 was found positively regulating auxin accumulation in lateral root primordia and lateral roots by enhancing local auxin biosynthesis, thus stimulating lateral root initiation and growth. We propose that AGL21 may be involved in various environmental and physiological signals mediated lateral root development and growth. PMID- 25122700 TI - Oculomotor task switching: alternating from a nonstandard to a standard response yields the unidirectional prosaccade switch-cost. AB - The completion of an antisaccade (i.e., a nonstandard task) lengthens the reaction time (RT) of a subsequent prosaccade: a behavioral phenomenon termed the unidirectional prosaccade switch-cost. One explanation for the unidirectional prosaccade switch-cost is suppressing a stimulus-driven prosaccade during the preceding antisaccade trial engenders a residual inhibition of the oculomotor networks that support prosaccade planning (i.e., the oculomotor inhibition hypothesis). Alternatively, the unidirectional prosaccade switch-cost may reflect the persistent activation of the antisaccade's nonstandard task rules (i.e., task set), which delays the planning of the next prosaccade (i.e., task-set inertia hypothesis). To determine which hypothesis provides the most parsimonious account for the unidirectional prosaccade switch-cost, participants alternated between pro- and antisaccades wherein task instructions (i.e., pro- and antisaccade) were provided before (i.e., classic cuing) or concurrent (i.e., delayed cuing) with response cuing. Importantly, pro- and antisaccades elicited via the delayed cuing condition required the suppression of a stimulus-driven prosaccade at response cuing (i.e., response suppression) to discern the appropriate to-be-performed task. Results showed that classic and delayed antisaccades, but not delayed prosaccades, lengthened the RT of subsequent prosaccades. That delayed prosaccades, which require response suppression for their successful execution, did not lengthen the RT of subsequent prosaccades indicates that the oculomotor inhibition hypothesis does not account for the unidirectional prosaccade switch cost. Instead, the current findings are in line with the assertion that the task set associated with a nonstandard antisaccade persists inertially and delays the planning of a subsequent prosaccade (i.e., task-set inertia hypothesis). PMID- 25122701 TI - Role of spinal bombesin-responsive neurons in nonhistaminergic itch. AB - Intrathecal administration of the neurotoxin bombesin-saporin reduces or abolishes pruritogen-evoked scratching behavior. We investigated whether spinal neurons that respond to intradermal (ID) injection of pruritogens also respond to spinal superfusion of bombesin and vice versa. Single-unit recordings were made from superficial lumbar spinal dorsal horn neurons in anesthetized mice. We identified neurons with three search strategies: 1) ID injection of the nonhistaminergic itch mediator chloroquine, 2) spinal superfusion of bombesin, and 3) noxious pinch. All units were tested with an array of itch mediators (chloroquine, histamine, SLIGRL, BAM8-22), algogens [capsaicin, allyl isothiocyanate (AITC)], and physical stimuli (brush, pinch, noxious heat, cooling) applied to the hindlimb receptive field. The vast majority of chloroquine-responsive units also responded to bombesin. Of 26 chloroquine sensitive units tested, most responded to SLIGRL, half responded to histamine and/or BAM8-22, and most responded to capsaicin and/or AITC as well as noxious thermal and mechanical stimuli. Of 29 bombesin-responsive units, a large majority also responded to other itch mediators as well as AITC, capsaicin, and noxious thermal and mechanical stimuli. Responses to successive applications of bombesin exhibited tachyphylaxis. In contrast, of 36 units responsive to noxious pinch, the majority (67%) did not respond to ID chloroquine or spinal bombesin. It is suggested that chloroquine- and bombesin-sensitive spinal neurons signal itch from the skin. PMID- 25122703 TI - Radial-tangential anisotropy of crowding in the early visual areas. AB - Crowding, the inability to recognize an individual object in clutter (Bouma H. Nature 226: 177-178, 1970), is considered a major impediment to object recognition in peripheral vision. Despite its significance, the cortical loci of crowding are not well understood. In particular, the role of the primary visual cortex (V1) remains unclear. Here we utilize a diagnostic feature of crowding to identify the earliest cortical locus of crowding. Controlling for other factors, radially arranged flankers induce more crowding than tangentially arranged ones (Toet A, Levi DM. Vision Res 32: 1349-1357, 1992). We used functional magnetic resonance imaging (fMRI) to measure the change in mean blood oxygenation level dependent (BOLD) response due to the addition of a middle letter between a pair of radially or tangentially arranged flankers. Consistent with the previous finding that crowding is associated with a reduced BOLD response [Millin R, Arman AC, Chung ST, Tjan BS. Cereb Cortex (July 5, 2013). doi:10.1093/cercor/bht159], we found that the BOLD signal evoked by the middle letter depended on the arrangement of the flankers: less BOLD response was associated with adding the middle letter between radially arranged flankers compared with adding it between tangentially arranged flankers. This anisotropy in BOLD response was present as early as V1 and remained significant in downstream areas. The effect was observed while subjects' attention was diverted away from the testing stimuli. Contrast detection threshold for the middle letter was unaffected by flanker arrangement, ruling out surround suppression of contrast response as a major factor in the observed BOLD anisotropy. Our findings support the view that V1 contributes to crowding. PMID- 25122702 TI - Adaptation of high-gamma responses in human auditory association cortex. AB - This study investigates adaptation of high-frequency cortical responses [>60 Hz; high-gamma (HG)] to simple and complex sounds in human nonprimary auditory cortex. We used intracranial electrocorticographic recordings to measure event related changes in HG power as a function of stimulus probability. Tone and speech stimuli were presented in a series of traditional oddball and control paradigms. We hypothesized that HG power attenuates with stimulus repetition over multiple concurrent time scales in auditory association cortex. Time-frequency analyses were performed to identify auditory-responsive sites. Single-trial analyses and quantitative modeling were then used to measure trial-to-trial changes in HG power for high (frequent), low (infrequent), and equal (control) stimulus probabilities. Results show strong reduction of HG responses to frequently repeated tones and speech, with no differences in responses to infrequent and equal-probability stimuli. Adaptation of the HG frequent response, and not stimulus-acoustic differences or deviance-detection enhancement effects, accounted for the differential responses observed for frequent and infrequent sounds. Adaptation of HG responses showed a rapid onset (less than two trials) with slower adaptation between consecutive, repeated trials (2-10 s) and across trials in a stimulus block (~7 min). The auditory-evoked N100 response also showed repetition-related adaptation, consistent with previous human scalp and animal single-unit recordings. These findings indicate that HG responses are highly sensitive to the regularities of simple and complex auditory events and show adaptation on multiple concurrent time scales in human auditory association cortex. PMID- 25122705 TI - Analysis of the long-term actions of gabapentin and pregabalin in dorsal root ganglia and substantia gelatinosa. AB - The alpha2delta-ligands pregabalin (PGB) and gabapentin (GBP) are used to treat neuropathic pain. We used whole cell recording to study their long-term effects on substantia gelatinosa and dorsal root ganglion (DRG) neurons. Spinal cord slices were prepared from embryonic day 13 rat embryos and maintained in organotypic culture for >5 wk (neuronal age equivalent to young adult rats). Exposure of similarly aged DRG neurons (dissociated and cultured from postnatal day 19 rats) to GBP or PGB for 5-6 days attenuated high-voltage-activated calcium channel currents (HVA ICa). Strong effects were seen in medium-sized and in small isolectin B4-negative (IB4-) DRG neurons, whereas large neurons and small neurons that bound isolectin B4 (IB4+) were hardly affected. GBP (100 MUM) or PGB (10 MUM) were less effective than 20 MUM Mn(2+) in suppression of HVA ICa in small DRG neurons. By contrast, 5-6 days of exposure to these alpha2delta-ligands was more effective than 20 MUM Mn(2+) in reducing spontaneous excitatory postsynaptic currents at synapses in substantia gelatinosa. Spinal actions of gabapentinoids cannot therefore be ascribed to decreased expression of HVA Ca(2+) channels in primary afferent nerve terminals. In substantia gelatinosa, 5-6 days of exposure to PGB was more effective in inhibiting excitatory synaptic drive to putative excitatory neurons than to putative inhibitory neurons. Although spontaneous inhibitory postsynaptic currents were also attenuated, the overall long-term effect of alpha2delta-ligands was to decrease network excitability as monitored by confocal Ca(2+) imaging. We suggest that selective actions of alpha2delta ligands on populations of DRG neurons may predict their selective attenuation of excitatory transmission onto excitatory vs. inhibitory neurons in substantia gelatinosa. PMID- 25122704 TI - Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats. AB - Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 +/- 0.4 vs. 2.44 +/- 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15-30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4 AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. PMID- 25122706 TI - Decoding stimulus duration from neural responses in the auditory midbrain. AB - Neurons with responses selective for the duration of an auditory stimulus are called duration-tuned neurons (DTNs). Temporal specificity in their spiking suggests that one function of DTNs is to encode stimulus duration; however, the efficacy of duration encoding by DTNs has yet to be investigated. Herein, we characterize the information content of individual cells and a population of DTNs from the mammalian inferior colliculus (IC) by measuring the stimulus-specific information (SSI) and estimated Fisher information (FI) of spike count responses. We found that SSI was typically greatest for those stimulus durations that evoked maximum spike counts, defined as best duration (BD) stimuli, and that FI was maximal for stimulus durations off BD where sensitivity to a change in duration was greatest. Using population data, we demonstrate that a maximum likelihood estimator (MLE) can accurately decode stimulus duration from evoked spike counts. We also simulated a two-alternative forced choice task by having MLE models decide whether two durations were the same or different. With this task we measured the just-noticeable difference threshold for stimulus duration and calculated the corresponding Weber fractions across the stimulus domain. Altogether, these results demonstrate that the spiking responses of DTNs from the mammalian IC contain sufficient information for the CNS to encode, decode, and discriminate behaviorally relevant auditory signal durations. PMID- 25122708 TI - Nerve growth factor alters the sensitivity of rat masseter muscle mechanoreceptors to NMDA receptor activation. AB - Intramuscular injection of nerve growth factor (NGF) into rat masseter muscle induces a local mechanical sensitization that is greater in female than in male rats. The duration of NGF-induced sensitization in male and female rats was associated with an increase in peripheral N-methyl-d-aspartate (NMDA) receptor expression by masseter muscle afferent fibers that began 3 days postinjection. Here, we investigated the functional consequences of increased NMDA expression on the response properties of masseter muscle mechanoreceptors. In vivo extracellular single-unit electrophysiological recordings of trigeminal ganglion neurons innervating the masseter muscle were performed in anesthetized rats 3 days after NGF injection (25 MUg/ml, 10 MUl) into the masseter muscle. Mechanical activation threshold was assessed before and after intramuscular injection of NMDA. NMDA injection induced mechanical sensitization in both sexes that was increased significantly following NGF injection in the male rats but not in the female rats. However, in female but not male rats, further examination found that preadministration of NGF induced a greater sensitization in slow Adelta-fibers (2 7 m/s) than fast Adelta-fibers (7-12 m/s). This suggests that preadministration of NGF had a different effect on slowly conducting mechanoreceptors in the female rats compared with the male rats. Although previous studies have found an association between estrogenic tone and NMDA activity, no correlation was observed between NMDA-evoked mechanical sensitization and plasma estrogen level. This study suggests NGF alters NMDA-induced mechanical sensitization in the peripheral endings of masseter mechanoreceptors in a sexually dimorphic manner. PMID- 25122709 TI - Visual selectivity for heading in the macaque ventral intraparietal area. AB - The patterns of optic flow seen during self-motion can be used to determine the direction of one's own heading. Tracking eye movements which typically occur during everyday life alter this task since they add further retinal image motion and (predictably) distort the retinal flow pattern. Humans employ both visual and nonvisual (extraretinal) information to solve a heading task in such case. Likewise, it has been shown that neurons in the monkey medial superior temporal area (area MST) use both signals during the processing of self-motion information. In this article we report that neurons in the macaque ventral intraparietal area (area VIP) use visual information derived from the distorted flow patterns to encode heading during (simulated) eye movements. We recorded responses of VIP neurons to simple radial flow fields and to distorted flow fields that simulated self-motion plus eye movements. In 59% of the cases, cell responses compensated for the distortion and kept the same heading selectivity irrespective of different simulated eye movements. In addition, response modulations during real compared with simulated eye movements were smaller, being consistent with reafferent signaling involved in the processing of the visual consequences of eye movements in area VIP. We conclude that the motion selectivities found in area VIP, like those in area MST, provide a way to successfully analyze and use flow fields during self-motion and simultaneous tracking movements. PMID- 25122707 TI - Dopamine transporter gene susceptibility to methylation is associated with impulsivity in nonhuman primates. AB - Impulsivity, the predisposition to act without regard for negative consequences, is a characteristic of several psychiatric disorders and is thought to result in part from genetic variation in the untranslated region of the dopamine transporter (DAT) gene. As the exact link between genetic mutations and impulsivity has not been established, we used oculomotor behavior to characterize rhesus monkeys as impulsive or calm and genetic/epigenetic analysis and positron emission tomography (PET) to correlate phenotype to DAT genotype, DAT gene methylation, and DAT availability. We found three single nucleotide polymorphisms (SNPs) in the 3'-UTR of the DAT gene, one of which provided a potential site for methylation in the impulsive group. Bisulfite analysis showed that the DNA of the impulsive but not the calm subjects was methylated at one SNP. Because genetic/epigenetic modifications could lead to differences in protein expression, we measured DAT availability using [(18)F]2beta-carbomethoxy-3beta-(4 chlorophenyl)-8-(2-fluoroethyl)-nortropane ([(18)F]FECNT) PET and found higher DAT availability in the internal globus pallidus, an output nucleus of the basal ganglia, of the impulsive group. Higher DAT availability lowers dopamine levels, potentially altering neuronal circuits involved in the initiation of action, thus contributing to the impulsive phenotype. The association between increased methylation in the DAT gene and greater DAT availability suggests that mutations to the regulatory portion of the DAT gene lead to a susceptibility to epigenetic modification resulting in a discrete behavioral phenotype. PMID- 25122710 TI - Low-intensity electric fields induce two distinct response components in neocortical neuronal populations. AB - Low-intensity alternating electric fields applied to the scalp are capable of modulating cortical activity and brain functions, but the underlying mechanisms remain largely unknown. Here, we report two distinct components of voltage sensitive dye signals induced by low-intensity, alternating electric fields in rodent cortical slices: a "passive component," which corresponds to membrane potential changes directly induced by the electric field; and an "active component," which is a widespread depolarization that is dependent on excitatory synaptic transmission. The passive component is stationary, with amplitude and phase accurately reflecting the cortical cytoarchitecture. In contrast, the active component is initiated from a local "hot spot" of activity and spreads to a large population as a propagating wave with rich local dynamics. The propagation of the active component may play a role in modulating large-scale cortical activity by spreading a low level of excitation from a small initiation point to a vast neuronal population. PMID- 25122711 TI - Effects of millimeter wave irradiation and equivalent thermal heating on the activity of individual neurons in the leech ganglion. AB - Many of today's radiofrequency-emitting devices in telecommunication, telemedicine, transportation safety, and security/military applications use the millimeter wave (MMW) band (30-300 GHz). To evaluate the biological safety and possible applications of this radiofrequency band for neuroscience and neurology, we have investigated the physiological effects of low-intensity 60-GHz electromagnetic irradiation on individual neurons in the leech midbody ganglia. We applied incident power densities of 1, 2, and 4 mW/cm(2) to the whole ganglion for a period of 1 min while recording the action potential with a standard sharp electrode electrophysiology setup. For comparison, the recognized U.S. safe exposure limit is 1 mW/cm(2) for 6 min. During the exposure to MMWs and gradual bath heating at a rate of 0.04 degrees C/s (2.4 degrees C/min), the ganglionic neurons exhibited similar dose-dependent hyperpolarization of the plasma membrane and decrease in the action potential amplitude. However, narrowing of the action potential half-width during MMW irradiation at 4 mW/cm(2) was 5 times more pronounced compared with that during equivalent bath heating of 0.6 degrees C. Even more dramatic difference in the effects of MMW irradiation and bath heating was noted in the firing rate, which was suppressed at all applied MMW power densities and increased in a dose-dependent manner during gradual bath heating. The mechanism of enhanced narrowing of action potentials and suppressed firing by MMW irradiation, compared with that by gradual bath heating, is hypothesized to involve specific coupling of MMW energy with the neuronal plasma membrane. PMID- 25122712 TI - The irregular firing properties of thalamic head direction cells mediate turn specific modulation of the directional tuning curve. AB - Head direction cells encode an animal's heading in the horizontal plane. However, it is not clear why the directionality of a cell's mean firing rate differs for clockwise, compared with counterclockwise, head turns (this difference is known as the "separation angle") in anterior thalamus. Here we investigated in freely behaving rats whether intrinsic neuronal firing properties are linked to this phenomenon. We found a positive correlation between the separation angle and the spiking variability of thalamic head direction cells. To test whether this link is driven by hyperpolarization-inducing currents, we investigated the effect of thalamic reticular inhibition during high-voltage spindles on directional spiking. While the selective directional firing of thalamic neurons was preserved, we found no evidence for entrainment of thalamic head direction cells by high-voltage spindle oscillations. We then examined the role of depolarization inducing currents in the formation of separation angle. Using a single compartment Hodgkin-Huxley model, we show that modeled neurons fire with higher frequencies during the ascending phase of sinusoidal current injection (mimicking the head direction tuning curve) when simulated with higher high-threshold calcium channel conductance. These findings demonstrate that the turn-specific encoding of directional signal strongly depends on the ability of thalamic neurons to fire irregularly in response to sinusoidal excitatory activation. Another crucial factor for inducing phase lead to sinusoidal current injection was the presence of spike-frequency adaptation current in the modeled neurons. Our data support a model in which intrinsic biophysical properties of thalamic neurons mediate the physiological encoding of directional information. PMID- 25122715 TI - Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury. AB - In humans, a chronic spinal cord injury (SCI) impairs the excitability of pathways mediating early flexor reflexes and increases the excitability of late, long-lasting flexor reflexes. We hypothesized that in individuals with SCI, locomotor training will alter the behavior of these spinally mediated reflexes. Nine individuals who had either chronic clinically motor complete or incomplete SCI received an average of 44 locomotor training sessions. Flexor reflexes, elicited via sural nerve stimulation of the right or left leg, were recorded from the ipsilateral tibialis anterior (TA) muscle before and after body weight support (BWS)-assisted treadmill training. The modulation pattern of the ipsilateral TA responses following innocuous stimulation of the right foot was also recorded in 10 healthy subjects while they stepped at 25% BWS to investigate whether body unloading during walking affects the behavior of these responses. Healthy subjects did not receive treadmill training. We observed a phase dependent modulation of early TA flexor reflexes in healthy subjects with reduced body weight during walking. The early TA flexor reflexes were increased at heel contact, progressively decreased during the stance phase, and then increased throughout the swing phase. In individuals with SCI, locomotor training induced the reappearance of early TA flexor reflexes and changed the amplitude of late TA flexor reflexes during walking. Both early and late TA flexor reflexes were modulated in a phase-dependent pattern after training. These new findings support the adaptive capability of the injured nervous system to return to a prelesion excitability and integration state. PMID- 25122714 TI - Minimum conditions for the induction of cortical spreading depression in brain slices. AB - Cortical spreading depression (CSD) occurs during various forms of brain injury such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought to be the mechanism of the migraine aura. It is therefore expected to occur over a range of conditions including the awake behaving state. Yet it is unclear how such a massive depolarization could occur under relatively benign conditions. Using a microfluidic device with focal stimulation capability in a mouse brain slice model, we varied extracellular potassium concentration as well as the area exposed to increased extracellular potassium to determine the minimum conditions necessary to elicit CSD. Importantly, we focused on potassium levels that are physiologically plausible (<=145 mM; the intracellular potassium concentration). We found a strong correlation between the threshold concentration and the slice area exposed to increased extracellular potassium: minimum area of exposure was needed with the highest potassium concentration, while larger areas were needed at lower concentrations. We also found that moderate elevations of extracellular potassium were able to elicit CSD in relatively small estimated tissue volumes that might be activated under noninjury conditions. Our results thus show that CSD may be inducible under the conditions that expected in migraine aura as well as those related to brain trauma. PMID- 25122716 TI - Opposed optimal strategies of weighting somatosensory inputs for planning reaching movements toward visual and proprioceptive targets. AB - Behavioral studies have suggested that the brain uses a visual estimate of the hand to plan reaching movements toward visual targets and somatosensory inputs in the case of somatosensory targets. However, neural correlates for distinct coding of the hand according to the sensory modality of the target have not yet been identified. Here we tested the twofold hypothesis that the somatosensory input from the reaching hand is facilitated and inhibited, respectively, when planning movements toward somatosensory (unseen fingers) or visual targets. The weight of the somatosensory inputs was assessed by measuring the amplitude of the somatosensory evoked potential (SEP) resulting from vibration of the reaching finger during movement planning. The target sensory modality had no significant effect on SEP amplitude. However, Spearman's analyses showed significant correlations between the SEPs and reaching errors. When planning movements toward proprioceptive targets without visual feedback of the reaching hand, participants showing the greater SEPs were those who produced the smaller directional errors. Inversely, participants showing the smaller SEPs when planning movements toward visual targets with visual feedback of the reaching hand were those who produced the smaller directional errors. No significant correlation was found between the SEPs and radial or amplitude errors. Our results indicate that the sensory strategy for planning movements is highly flexible among individuals and also for a given sensory context. Most importantly, they provide neural bases for the suggestion that optimization of movement planning requires the target and the reaching hand to both be represented in the same sensory modality. PMID- 25122713 TI - Modulation of motoneuron firing by recurrent inhibition in the adult rat in vivo. AB - Recent reports show that synaptic inhibition can modulate postsynaptic spike timing without having strong effects on firing rate. Thus synaptic inhibition can achieve multiplicity in neural circuit operation through variable modulation of postsynaptic firing rate vs. timing. We tested this possibility for recurrent inhibition (RI) of spinal motoneurons. In in vivo electrophysiological studies of adult Wistar rats anesthetized by isoflurane, we examined repetitive firing of individual lumbosacral motoneurons recorded in current clamp and modulated by synchronous antidromic electrical stimulation of multiple motor axons and their centrally projecting collateral branches. Antidromic stimulation produced recurrent inhibitory postsynaptic potentials (RIPSPs) having properties similar to those detailed in the cat. Although synchronous RI produced marked short-term modulation of motoneuron spike timing and instantaneous firing rate, there was little or no suppression of average firing rate. The bias in firing modulation of timing over average rate was observed even for high-frequency RI stimulation (100 Hz), perhaps because of the brevity of RIPSPs, which were more than twofold shorter during motoneuron firing compared with rest. These findings demonstrate that RI in the mammalian spinal cord has the capacity to support and not impede heightened motor pool activity, possibly during rapid, forceful movements. PMID- 25122718 TI - Learning-related neuronal activity in the ventral lateral geniculate nucleus during associative cerebellar learning. AB - During delay eyeblink conditioning, rats learn to produce an eyelid-closure conditioned response (CR) to a conditioned stimulus (CS), such as a light, which precedes and coterminates with an unconditioned stimulus (US). Previous studies have suggested that the ventral lateral geniculate nucleus (LGNv) might play an important role in visual eyeblink conditioning by supplying visual sensory input to the pontine nuclei (PN) and also receiving feedback from the cerebellum. No prior study has investigated LGNv neuronal activity during eyeblink conditioning. The present study used multiple tetrodes to monitor single-unit activity in the rat LGNv during pre-exposure (CS only), unpaired CS/US, and paired CS-US training conditions. This behavioral-training sequence was used to investigate nonassociative- and associative-driven neuronal activity in the LGNv during training. LGNv neuronal activity habituated during unpaired training and then recovered from habituation during subsequent paired training, which may indicate that the LGNv plays a role in attention to the CS. The amplitude of LGNv neuronal activity correlated with CR production during paired but not unpaired CS/US training. Cerebellar feedback to the LGNv may play a role in modulating LGNv activity and attention to the CS during paired training. Based on the present findings, we hypothesize that the role of LGNv in visual eyeblink conditioning goes beyond simply routing visual CS information to the PN and involves modulation of attention. PMID- 25122720 TI - High-quality 3-dimensional imaging for patients with anomalous pulmonary veins. AB - The branching pattern of pulmonary veins exhibits many variations. Here we describe 2 patients with lung malignancies who were found to have pulmonary vein anomalies. We performed video-assisted thoracoscopic lobectomies based on preoperative simulations by 3-dimensional computed tomography. Using 3 dimensional computed tomography, a surgeon can easily construct digital images of the patient's pulmonary vessels within a few minutes. Simulation using 3 dimensional computed tomography imaging is useful for further understanding of the surgical anatomy. PMID- 25122719 TI - Gender Differences in Health Literacy Among Korean Adults: Do Women Have a Higher Level of Health Literacy Than Men? AB - The role of gender in determining the level of health literacy in Korean adults is unclear. This study aimed to investigate the level of health literacy in Korean adults and identify factors associated with health literacy by gender. This study employed a cross-sectional survey design with a convenient sample of 585 community-dwelling Korean adults age19 years and older. Health literacy was measured by using eight items selected from Chew et al.'s 16-question self reported health literacy measure. In accordance with Andersen's health behavior model, predisposing, enabling, and need factors were included in the multiple regression model. Women indicated a higher level of health literacy than men in understanding medical forms, directions on medication bottles, and written information offered by health care providers. Additionally, for Korean women, a higher level of health literacy was associated with attaining a higher education level and having a consistent place to receive care. Unmarried men and men who had higher self-rated health reported a higher level of health literacy compared with their counterparts. Lower level of depression and higher monthly income were significantly linked to a higher level of health literacy in both men and women. This study has established the importance of gender differences in health literacy and suggests gender-specific intervention may be warranted to reduce the existing gap in health literacy in both Korean men and women. Future research should replicate this study to confirm whether or not our finding is an international phenomenon. PMID- 25122721 TI - Genetic polymorphisms in preoperative myocardial infarction. AB - OBJECTIVE: This study compared plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in patients with myocardial infarction with ST-segment elevation before undergoing to coronary artery bypass grafting, and in patients who had previously undergone coronary artery bypass grafting. METHOD: Seventy patients with myocardial infarction with ST-segment elevation, scheduled to undergo coronary artery bypass grafting, were included in the study group, and 70 patients who had previously undergone coronary artery bypass grafting were included in the control group. Genetic polymorphisms were determined using real-time polymerase chain reaction methods. RESULTS: Our data showed that there were no significant differences in plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms or allele frequencies between the 2 groups. CONCLUSION: Plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase C677T and A1298C polymorphisms were not associated risk factors in patients who had myocardial infarction with ST-segment elevation and planned to have coronary artery bypass grafting. PMID- 25122717 TI - Elevated serotonergic signaling amplifies synaptic noise and facilitates the emergence of epileptiform network oscillations. AB - Serotonin fibers densely innervate the cortical sheath to regulate neuronal excitability, but its role in shaping network dynamics remains undetermined. We show that serotonin provides an excitatory tone to cortical neurons in the form of spontaneous synaptic noise through 5-HT3 receptors, which is persistent and can be augmented using fluoxetine, a selective serotonin re-uptake inhibitor. Augmented serotonin signaling also increases cortical network activity by enhancing synaptic excitation through activation of 5-HT2 receptors. This in turn facilitates the emergence of epileptiform network oscillations (10-16 Hz) known as fast runs. A computational model of cortical dynamics demonstrates that these two combined mechanisms, increased background synaptic noise and enhanced synaptic excitation, are sufficient to replicate the emergence fast runs and their statistics. Consistent with these findings, we show that blocking 5-HT2 receptors in vivo significantly raises the threshold for convulsant-induced seizures. PMID- 25122722 TI - A case of right superior vena cava draining into the left atrial roof. AB - We report the multidisciplinary consideration in a case of right superior vena cava draining into the left atrial roof. A 12-year-old boy was diagnosed with a sinus venosus-type atrial septal defect associated with anomalous right upper pulmonary venous return. However, intraoperative inspection showed the right superior vena cava draining into the left atrial roof, associated with anomalous right upper pulmonary venous return. An anatomical radical operation was performed using a modified conventional technique. PMID- 25122723 TI - Single coronary artery anomaly without previous myocardial infarction does not cause ischemic mitral insufficiency. PMID- 25122724 TI - Opioid therapy for knee osteoarthritis and postoperative persistent pain after knee arthroplasty. PMID- 25122725 TI - Mortality in patients with giant cell arteritis. AB - OBJECTIVE: The aim of this study was to examine whether GCA is associated with increased mortality. METHODS: We conducted a nationwide population-based cohort study including all individuals who between 1993 and 2011 were registered in the Danish National Hospital Register and the Danish Pathology Register with a biopsy proven diagnosis of GCA (n = 1787). Through the Danish Civil Registration System we identified a comparison cohort of 33 953 persons from the background population, individually matched on age and sex. Data on causes of death were obtained from the Danish Registry of Causes of Death. We used Poisson regression to determine mortality rate ratios as estimates of relative risk of death and specific causes of death. RESULTS: Compared with the general population, the relative risk (RR) of death in patients diagnosed with GCA was 1.17 (95% CI 1.01, 1.36) and 1.22 (95% CI 1.05, 1.41) 0-2 years and >10 years after diagnosis, respectively, whereas we observed no increased mortality during the follow-up period of 2-10 years [RR 0.96 (95% CI 0.88, 1.05)]. The increased mortality during the first 2 years of follow-up was mainly due to diseases of the circulatory system, including aortic aneurisms. CONCLUSION: GCA is associated with slightly increased early and late mortality. PMID- 25122726 TI - The global anti-phospholipid syndrome score in primary APS. AB - OBJECTIVE: The aim of this study was to evaluate the clinical relevance of the global APS score (GAPSS) in a cohort of primary APS patients. METHODS: This study included 62 consecutive patients with primary APS. Data on clinical manifestations, conventional cardiovascular risk factors and aPL profile were collected. The GAPSS was calculated for each patient by adding together the points corresponding to the risk factors, based on a linear transformation derived from the beta regression coefficient as follows: 3 for hyperlipidaemia, 1 for arterial hypertension, 5 for aCL IgG/IgM, 4 for anti-beta2 glycoprotein I IgG/IgM, 3 for aPS-PT IgG/IgM and 4 for LA. RESULTS: Higher GAPSS values were seen in patients who experienced thrombosis alone when compared with those with pregnancy loss alone [11.5 (S.D. 4.6) and 8.7 (S.D. 3.2), P = 0.04]. Patients with both thrombosis and pregnancy loss showed higher GAPSS than those with pregnancy loss alone [12.5 (S.D. 4.6) vs 8.7 (S.D. 3.2), P = 0.02]. Higher GAPSS values were also shown after subgrouping for the site of thrombosis when compared with pregnancy loss alone [12.2 (S.D. 5.2) for arterial thrombosis, 12.0 (S.D. 4.0) for venous vs 8.7 (S.D. 3.2), P = 0.02 and P = 0.04, respectively]. Patients with thrombotic recurrences showed higher GAPSS values when compared with those without recurrence [13.7 (S.D. 3.1) vs 9.4 (S.D. 3.9), P = 0.02]. This was also seen when comparing recurrences vs no recurrences independently of the site of the thrombotic event [13.9 (S.D. 3.6) vs 11.0 (S.D. 4.3), P = 0.01 for arterial and 13.6 (S.D. 2.18) vs 8.91 (S.D. 3.6), P < 0.01 for venous thrombosis]. GAPSS values >=11 were strongly associated with a higher risk of recurrence [odds ratio (OR) 18.27 (95% CI 3.74, 114.5) for a cut-off of 11, OR 20.64 (95% CI 3.92, 185.92) for a cut-off of 12 and 21.64 (95% CI 3.89, 189.56) for a cut-off of 15]. GAPSS values >=11 seemed to have the best risk accuracy in terms of sensitivity and specificity. CONCLUSION: The GAPSS is demonstrated to be a valid tool for a substantial improvement in risk stratification for thrombosis in primary APS. PMID- 25122728 TI - Tall cell variant of papillary thyroid carcinoma in children: report of three cases with long-term follow-up from a single institution. AB - Papillary thyroid carcinoma (PTC), tall cell (TC) variant, is exceptional in children. In adults it represents about 20% of PTCs, featuring a high-risk neoplasm, with a 4-fold risk of relapse and a 20-fold relapse-related risk of death. Out of 42 cases of pediatric PTCs, we found 3 cases of PTC-TC (7%) with clinical data at onset and follow-up up to June 2014. They were 3 females aged 13, 15, and 15 years. Local extrathyroid extension was present in 2 cases. Neither nodal nor distant metastases were found. Two patients underwent hemithyroidectomy and 1 patient a total thyroidectomy, followed in all cases by life-long suppressive hormonal therapy. On follow-up, the patients were alive and well after 29, 24, and 29 years, respectively. The rarity of PTC-TC in children was confirmed. The behavior was indolent after a median follow-up of about 29 years, following treatment with hemithyroidectomy in 2 cases and controlled by suppressive hormonal therapy. The results of this series, albeit small, suggest that TC morphology in PTC does not carry the same negative prognostic significance in children as it does in adults. A conservative approach should therefore be considered for these 'pediatric type' cases of this tumor type. PMID- 25122730 TI - Modigliani-like art in surgical pathology. PMID- 25122727 TI - Predictive impact on medium-term mortality of hematological parameters in Acute Coronary Syndromes: added value on top of GRACE risk score. AB - BACKGROUND: Red Cell Distribution Width (RDW) prognostic value in patients with Acute Coronary Syndrome (ACS) has been well validated whereas that of Platelet Distribution Width (PDW) is less well known. OBJECTIVES: Investigate the incremental prognostic value, on top of GRACE risk score, of a new variable resulting from the combination of RDW and PDW. METHODS: Consecutive patients with ACS. Complete blood count, with RDW and PDW, was obtained. Primary endpoint was one-year all-cause mortality and Cox regression models were used to measure the influence of RDW and PDW on patients' survival time. A new combination categorical variable (RDW/PDW) was created with both discretized RDW and PDW and logistic regression models were used. Predictive value and discriminative ability of the model with GRACE risk score alone and of the model with inclusion of RDW/PDW was assessed. RESULTS: We included 787 patients. Hospital and one-year mortality rates were 5.1% and 7.8%, respectively. Both continuous RDW and PDW were independent predictors of death. The best cut-off for RDW was 13.9%, and 14.5% for PDW. Inclusion of RDW/PDW in a model with GRACE risk score improved the AUC from 0.81 (95% CI 0.75-0.86) to 0.84 (95% CI 0.79-0.90) (p=0.024) with an improvement in total NRI (56%) and IDI (0.048). CONCLUSIONS: Simple markers such as RDW and PDW can be useful in risk stratification of death after ACS. Combining both markers with GRACE risk score improved the predictive value for all-cause mortality and reduced the estimated risk of those who did not die. PMID- 25122729 TI - Art and human expression in histology. PMID- 25122731 TI - Measuring progress in global health. PMID- 25122732 TI - Cognitive Testing to Identify Children With ADHD Who Do and Do Not Respond to Methylphenidate. AB - OBJECTIVE: To explore the utility of cognitive measures for predicting response of children and adolescents to methylphenidate (MPH). METHOD: Participants from the International Study to Predict Optimized Treatment-in ADHD (iSPOT-A) completed a cognitive test battery prior to receiving 6 weeks of MPH. The responder criterion was a 25% reduction in ADHD-Rating Scale-IV scores. Receiver Operator Characteristics (ROC) classified non-responders from responders with maximal sensitivity and specificity. RESULTS: Overall, 62% of participants responded to MPH. Response rates for ROC-identified groups ranged from 18% to 85%. Non-responders showed compromised cognition related to switching of attention, sustained attention, planning, and impulsivity. One group of responders were 10 years of age or older and had impaired switching of attention and impulsivity; a second group had enhanced switching of attention, normal or higher Continuous Performance Task (CPT) scores, and above average scores on digit span. CONCLUSION: Cognitive tests may provide a simple, low-cost tool for treatment planning for children and adolescents with ADHD. PMID- 25122733 TI - Researchers push back against overhauling clinical trials. PMID- 25122734 TI - Water pipe smoking: not risk free. PMID- 25122737 TI - Hormone therapy can wait in PSA-only relapse. PMID- 25122735 TI - Identifying cancer mutations as therapeutic targets. PMID- 25122739 TI - The enemy of my enemy is my friend: intraguild predation between invaders and natives facilitates coexistence with shared invasive prey. AB - Understanding and predicting the outcomes of biological invasions is challenging where multiple invader and native species interact. We hypothesize that antagonistic interactions between invaders and natives could divert their impact on subsequent invasive species, thus facilitating coexistence. From field data, we found that, when existing together in freshwater sites, the native amphipod Gammarus duebeni celticus and a previous invader G. pulex appear to facilitate the establishment of a second invader, their shared prey Crangonyx pseudogracilis. Indeed, the latter species was rarely found at sites where each Gammarus species was present on its own. Experiments indicated that this may be the result of G. d. celticus and G. pulex engaging in more intraguild predation (IGP) than cannibalism; when the 'enemy' of either Gammarus species was present, that is, the other Gammarus species, C. pseudogracilis significantly more often escaped predation. Thus, the presence of mutual enemies and the stronger inter- than intraspecific interactions they engage in can facilitate other invaders. With some invasive species such as C. pseudogracilis having no known detrimental effects on native species, and indeed having some positive ecological effects, we also conclude that some invasions could promote biodiversity and ecosystem functioning. PMID- 25122740 TI - Preterm birth is associated with an increased fundamental frequency of spontaneous crying in human infants at term-equivalent age. AB - Human infant crying has been researched as a non-invasive tool for assessing neurophysiological states at an early developmental stage. Little is known about the acoustic features of spontaneous cries in preterm infants, although their pain-induced cries are at a higher fundamental frequency (F0) before term equivalent age. In this study, we investigated the effects of gestational age, body size at recording and intrauterine growth retardation (IUGR) on the F0 of spontaneous cries in healthy preterm and full-term infants at term-equivalent age. We found that shorter gestational age was significantly associated with higher F0, although neither smaller body size at recording nor IUGR was related to increased F0 in preterm infants. These findings suggest that the increased F0 of spontaneous cries is not caused by their smaller body size, but instead might be caused by more complicated neurophysiological states owing to their different intrauterine and extrauterine experiences. PMID- 25122741 TI - Size matters: plasticity in metabolic scaling shows body-size may modulate responses to climate change. AB - Variability in metabolic scaling in animals, the relationship between metabolic rate ( R: ) and body mass ( M: ), has been a source of debate and controversy for decades. R: is proportional to MB: , the precise value of B: much debated, but historically considered equal in all organisms. Recent metabolic theory, however, predicts B: to vary among species with ecology and metabolic level, and may also vary within species under different abiotic conditions. Under climate change, most species will experience increased temperatures, and marine organisms will experience the additional stressor of decreased seawater pH ('ocean acidification'). Responses to these environmental changes are modulated by myriad species-specific factors. Body-size is a fundamental biological parameter, but its modulating role is relatively unexplored. Here, we show that changes to metabolic scaling reveal asymmetric responses to stressors across body-size ranges; B: is systematically decreased under increasing temperature in three grazing molluscs, indicating smaller individuals were more responsive to warming. Larger individuals were, however, more responsive to reduced seawater pH in low temperatures. These alterations to the allometry of metabolism highlight abiotic control of metabolic scaling, and indicate that responses to climate warming and ocean acidification may be modulated by body-size. PMID- 25122742 TI - Efficient nearest neighbors via robust sparse hashing. AB - This paper presents a new nearest neighbor (NN) retrieval framework: robust sparse hashing (RSH). Our approach is inspired by the success of dictionary learning for sparse coding. Our key idea is to sparse code the data using a learned dictionary, and then to generate hash codes out of these sparse codes for accurate and fast NN retrieval. But, direct application of sparse coding to NN retrieval poses a technical difficulty: when data are noisy or uncertain (which is the case with most real-world data sets), for a query point, an exact match of the hash code generated from the sparse code seldom happens, thereby breaking the NN retrieval. Borrowing ideas from robust optimization theory, we circumvent this difficulty via our novel robust dictionary learning and sparse coding framework called RSH, by learning dictionaries on the robustified counterparts of the perturbed data points. The algorithm is applied to NN retrieval on both simulated and real-world data. Our results demonstrate that RSH holds significant promise for efficient NN retrieval against the state of the art. PMID- 25122743 TI - Monte Carlo non-local means: random sampling for large-scale image filtering. AB - We propose a randomized version of the nonlocal means (NLM) algorithm for large scale image filtering. The new algorithm, called Monte Carlo nonlocal means (MCNLM), speeds up the classical NLM by computing a small subset of image patch distances, which are randomly selected according to a designed sampling pattern. We make two contributions. First, we analyze the performance of the MCNLM algorithm and show that, for large images or large external image databases, the random outcomes of MCNLM are tightly concentrated around the deterministic full NLM result. In particular, our error probability bounds show that, at any given sampling ratio, the probability for MCNLM to have a large deviation from the original NLM solution decays exponentially as the size of the image or database grows. Second, we derive explicit formulas for optimal sampling patterns that minimize the error probability bound by exploiting partial knowledge of the pairwise similarity weights. Numerical experiments show that MCNLM is competitive with other state-of-the-art fast NLM algorithms for single-image denoising. When applied to denoising images using an external database containing ten billion patches, MCNLM returns a randomized solution that is within 0.2 dB of the full NLM solution while reducing the runtime by three orders of magnitude. PMID- 25122744 TI - Mycobacterium RbpA cooperates with the stress-response sigmaB subunit of RNA polymerase in promoter DNA unwinding. AB - RbpA, a transcriptional activator that is essential for Mycobacterium tuberculosis replication and survival during antibiotic treatment, binds to RNA polymerase (RNAP) in the absence of promoter DNA. It has been hypothesized that RbpA stimulates housekeeping gene expression by promoting assembly of the sigma(A) subunit with core RNAP. Here, using a purified in vitro transcription system of M. tuberculosis, we show that RbpA functions in a promoter-dependent manner as a companion of RNAP essential for promoter DNA unwinding and formation of the catalytically active open promoter complex (RPo). Screening for RbpA activity using a full panel of the M. tuberculosis sigma subunits demonstrated that RbpA targets sigma(A) and stress-response sigma(B), but not the alternative sigma subunits from the groups 3 and 4. In contrast to sigma(A), the sigma(B) subunit activity displayed stringent dependency upon RbpA. These results suggest that RbpA-dependent control of RPo formation provides a mechanism for tuning gene expression during the switch between different physiological states, and in the stress response. PMID- 25122745 TI - Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation. AB - Artificial transcription factors (ATFs) and genomic nucleases based on a DNA binding platform consisting of multiple zinc finger domains are currently being developed for clinical applications. However, no genome-wide investigations into their binding specificity have been performed. We have created six-finger ATFs to target two different 18 nt regions of the human SOX2 promoter; each ATF is constructed such that it contains or lacks a super KRAB domain (SKD) that interacts with a complex containing repressive histone methyltransferases. ChIP seq analysis of the effector-free ATFs in MCF7 breast cancer cells identified thousands of binding sites, mostly in promoter regions; the addition of an SKD domain increased the number of binding sites ~ 5-fold, with a majority of the new sites located outside of promoters. De novo motif analyses suggest that the lack of binding specificity is due to subsets of the finger domains being used for genomic interactions. Although the ATFs display widespread binding, few genes showed expression differences; genes repressed by the ATF-SKD have stronger binding sites and are more enriched for a 12 nt motif. Interestingly, epigenetic analyses indicate that the transcriptional repression caused by the ATF-SKD is not due to changes in active histone modifications. PMID- 25122747 TI - Systematic exploration of a class of hydrophobic unnatural base pairs yields multiple new candidates for the expansion of the genetic alphabet. AB - We have developed a family of unnatural base pairs (UBPs), which rely on hydrophobic and packing interactions for pairing and which are well replicated and transcribed. While the pair formed between d5SICS and dNaM (d5SICS-dNaM) has received the most attention, and has been used to expand the genetic alphabet of a living organism, recent efforts have identified dTPT3-dNaM, which is replicated with even higher fidelity. These efforts also resulted in more UBPs than could be independently analyzed, and thus we now report a PCR-based screen to identify the most promising. While we found that dTPT3-dNaM is generally the most promising UBP, we identified several others that are replicated nearly as well and significantly better than d5SICS-dNaM, and are thus viable candidates for the expansion of the genetic alphabet of a living organism. Moreover, the results suggest that continued optimization should be possible, and that the putatively essential hydrogen-bond acceptor at the position ortho to the glycosidic linkage may not be required. These results clearly demonstrate the generality of hydrophobic forces for the control of base pairing within DNA, provide a wealth of new structure-activity relationship data and importantly identify multiple new candidates for in vivo evaluation and further optimization. PMID- 25122746 TI - Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector. AB - Engineered DNA-binding proteins that manipulate the human genome and transcriptome have enabled rapid advances in biomedical research. In particular, the RNA-guided CRISPR/Cas9 system has recently been engineered to create site specific double-strand breaks for genome editing or to direct targeted transcriptional regulation. A unique capability of the CRISPR/Cas9 system is multiplex genome engineering by delivering a single Cas9 enzyme and two or more single guide RNAs (sgRNAs) targeted to distinct genomic sites. This approach can be used to simultaneously create multiple DNA breaks or to target multiple transcriptional activators to a single promoter for synergistic enhancement of gene induction. To address the need for uniform and sustained delivery of multiplex CRISPR/Cas9-based genome engineering tools, we developed a single lentiviral system to express a Cas9 variant, a reporter gene and up to four sgRNAs from independent RNA polymerase III promoters that are incorporated into the vector by a convenient Golden Gate cloning method. Each sgRNA is efficiently expressed and can mediate multiplex gene editing and sustained transcriptional activation in immortalized and primary human cells. This delivery system will be significant to enabling the potential of CRISPR/Cas9-based multiplex genome engineering in diverse cell types. PMID- 25122748 TI - Probing the elastic limit of DNA bending. AB - Sharp bending of double-stranded DNA (dsDNA) plays an essential role in genome structure and function. However, the elastic limit of dsDNA bending remains controversial. Here, we measured the opening rates of small dsDNA loops with contour lengths ranging between 40 and 200 bp using single-molecule Fluorescence Resonance Energy Transfer. The relationship of loop lifetime to loop size revealed a critical transition in bending stress. Above the critical loop size, the loop lifetime changed with loop size in a manner consistent with elastic bending stress, but below it, became less sensitive to loop size, indicative of softened dsDNA. The critical loop size increased from ~ 60 bp to ~ 100 bp with the addition of 5 mM magnesium. We show that our result is in quantitative agreement with the kinkable worm-like chain model, and furthermore, can reproduce previously reported looping probabilities of dsDNA over the range between 50 and 200 bp. Our findings shed new light on the energetics of sharply bent dsDNA. PMID- 25122749 TI - Molecular insights into replication initiation by Qbeta replicase using ribosomal protein S1. AB - Ribosomal protein S1, consisting of six contiguous OB-folds, is the largest ribosomal protein and is essential for translation initiation in Escherichia coli. S1 is also one of the three essential host-derived subunits of Qbeta replicase, together with EF-Tu and EF-Ts, for Qbeta RNA replication in E. coli. We analyzed the crystal structure of Qbeta replicase, consisting of the virus encoded RNA-dependent RNA polymerase (beta-subunit), EF-Tu, EF-Ts and the N terminal half of S1, which is capable of initiating Qbeta RNA replication. Structural and biochemical studies revealed that the two N-terminal OB-folds of S1 anchor S1 onto the beta-subunit, and the third OB-fold is mobile and protrudes beyond the surface of the beta-subunit. The third OB-fold mainly interacts with a specific RNA fragment derived from the internal region of Qbeta RNA, and its RNA binding ability is required for replication initiation of Qbeta RNA. Thus, the third mobile OB-fold of S1, which is spatially anchored near the surface of the beta-subunit, primarily recruits the Qbeta RNA toward the beta-subunit, leading to the specific and efficient replication initiation of Qbeta RNA, and S1 functions as a replication initiation factor, beyond its established function in protein synthesis. PMID- 25122751 TI - Binding of the transcription factor Atf1 to promoters serves as a barrier to phase nucleosome arrays and avoid cryptic transcription. AB - Schizosaccharomyces pombe displays a large transcriptional response common to several stress conditions, regulated primarily by the transcription factor Atf1. Atf1-dependent promoters contain especially broad nucleosome depleted regions (NDRs) prior to stress imposition. We show here that basal binding of Atf1 to these promoters competes with histones to create wider NDRs at stress genes. Moreover, deletion of atf1 results in nucleosome disorganization specifically at stress coding regions and derepresses antisense transcription. Our data indicate that the transcription factor binding to promoters acts as an effective barrier to fix the +1 nucleosome and phase downstream nucleosome arrays to prevent cryptic transcription. PMID- 25122750 TI - Negative regulation of the interferon response by an interferon-induced long non coding RNA. AB - Long non-coding RNAs (lncRNAs) play critical roles in diverse cellular processes; however, their involvement in many critical aspects of the immune response including the interferon (IFN) response remains poorly understood. To address this gap, we compared the global gene expression pattern of primary human hepatocytes before and at three time points after treatment with IFN-alpha. Among ~ 200 IFN-induced lncRNAs, one transcript showed ~ 100-fold induction. This RNA, which we named lncRNA-CMPK2, was a spliced, polyadenylated nuclear transcript that was induced by IFN in diverse cell types from human and mouse. Similar to protein-coding IFN-stimulated genes (ISGs), its induction was dependent on JAK STAT signaling. Intriguingly, knockdown of lncRNA-CMPK2 resulted in a marked reduction in HCV replication in IFN-stimulated hepatocytes, suggesting that it could affect the antiviral role of IFN. We could show that lncRNA-CMPK2 knockdown resulted in upregulation of several protein-coding antiviral ISGs. The observed upregulation was caused by an increase in both basal and IFN-stimulated transcription, consistent with loss of transcriptional inhibition in knockdown cells. These results indicate that the IFN response involves a lncRNA-mediated negative regulatory mechanism. lncRNA-CMPK2 was strongly upregulated in a subset of HCV-infected human livers, suggesting a role in modulation of the IFN response in vivo. PMID- 25122752 TI - The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1. AB - Single-stranded DNA (ssDNA) at DNA ends is an important regulator of the DNA damage response. Resection, the generation of ssDNA, affects DNA damage checkpoint activation, DNA repair pathway choice, ssDNA-associated mutation and replication fork stability. In eukaryotes, extensive DNA resection requires the nuclease Exo1 and nuclease/helicase pair: Dna2 and Sgs1(BLM). How Exo1 and Dna2 Sgs1(BLM) coordinate during resection remains poorly understood. The DNA damage checkpoint clamp (the 9-1-1 complex) has been reported to play an important role in stimulating resection but the exact mechanism remains unclear. Here we show that the human 9-1-1 complex enhances the cleavage of DNA by both DNA2 and EXO1 in vitro, showing that the resection-stimulatory role of the 9-1-1 complex is direct. We also show that in Saccharomyces cerevisiae, the 9-1-1 complex promotes both Dna2-Sgs1 and Exo1-dependent resection in response to uncapped telomeres. Our results suggest that the 9-1-1 complex facilitates resection by recruiting both Dna2-Sgs1 and Exo1 to sites of resection. This activity of the 9-1-1 complex in supporting resection is strongly inhibited by the checkpoint adaptor Rad9(53BP1). Our results provide important mechanistic insights into how DNA resection is regulated by checkpoint proteins and have implications for genome stability in eukaryotes. PMID- 25122753 TI - An intensity ratio of interlocking loops determines circadian period length. AB - Circadian clocks allow organisms to orchestrate the daily rhythms in physiology and behaviors, and disruption of circadian rhythmicity can profoundly affect fitness. The mammalian circadian oscillator consists of a negative primary feedback loop and is associated with some 'auxiliary' loops. This raises the questions of how these interlocking loops coordinate to regulate the period and maintain its robustness. Here, we focused on the REV-ERBalpha/Cry1 auxiliary loop, consisting of Rev-Erbalpha/ROR-binding elements (RORE) mediated Cry1 transcription, coordinates with the negative primary feedback loop to modulate the mammalian circadian period. The silicon simulation revealed an unexpected rule: the intensity ratio of the primary loop to the auxiliary loop is inversely related to the period length, even when post-translational feedback is fixed. Then we measured the mRNA levels from two loops in 10-mutant mice and observed the similar monotonic relationship. Additionally, our simulation and the experimental results in human osteosarcoma cells suggest that a coupling effect between the numerator and denominator of this intensity ratio ensures the robustness of circadian period and, therefore, provides an efficient means of correcting circadian disorders. This ratio rule highlights the contribution of the transcriptional architecture to the period dynamics and might be helpful in the construction of synthetic oscillators. PMID- 25122754 TI - DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells. AB - The 5'-3' resection of DNA ends is a prerequisite for the repair of DNA double strand breaks by homologous recombination, microhomology-mediated end joining, and single strand annealing. Recent studies in yeast have shown that, following initial DNA end processing by the Mre11-Rad50-Xrs2 complex and Sae2, the extension of resection tracts is mediated either by exonuclease 1 or by combined activities of the RecQ family DNA helicase Sgs1 and the helicase/endonuclease Dna2. Although human DNA2 has been shown to cooperate with the BLM helicase to catalyze the resection of DNA ends, it remains a matter of debate whether another human RecQ helicase, WRN, can substitute for BLM in DNA2-catalyzed resection. Here we present evidence that WRN and BLM act epistatically with DNA2 to promote the long-range resection of double strand break ends in human cells. Our biochemical experiments show that WRN and DNA2 interact physically and coordinate their enzymatic activities to mediate 5'-3' DNA end resection in a reaction dependent on RPA. In addition, we present in vitro and in vivo data suggesting that BLM promotes DNA end resection as part of the BLM-TOPOIIIalpha-RMI1-RMI2 complex. Our study provides new mechanistic insights into the process of DNA end resection in mammalian cells. PMID- 25122755 TI - Kinesin-2 KIF3AB exhibits novel ATPase characteristics. AB - KIF3AB is an N-terminal processive kinesin-2 family member best known for its role in intraflagellar transport. There has been significant interest in KIF3AB in defining the key principles that underlie the processivity of KIF3AB in comparison with homodimeric processive kinesins. To define the ATPase mechanism and coordination of KIF3A and KIF3B stepping, a presteady-state kinetic analysis was pursued. For these studies, a truncated murine KIF3AB was generated. The results presented show that microtubule association was fast at 5.7 MUm(-1) s( 1), followed by rate-limiting ADP release at 12.8 s(-1). ATP binding at 7.5 MUm( 1) s(-1) was followed by an ATP-promoted isomerization at 84 s(-1) to form the intermediate poised for ATP hydrolysis, which then occurred at 33 s(-1). ATP hydrolysis was required for dissociation of the microtubule.KIF3AB complex, which was observed at 22 s(-1). The dissociation step showed an apparent affinity for ATP that was very weak (K1/2,ATP at 133 MUm). Moreover, the linear fit of the initial ATP concentration dependence of the dissociation kinetics revealed an apparent second-order rate constant at 0.09 MUm(-1) s(-1), which is inconsistent with fast ATP binding at 7.5 MUm(-1) s(-1) and a Kd ,ATP at 6.1 MUm. These results suggest that ATP binding per se cannot account for the apparent weak K1/2,ATP at 133 MUm. The steady-state ATPase Km ,ATP, as well as the dissociation kinetics, reveal an unusual property of KIF3AB that is not yet well understood and also suggests that the mechanochemistry of KIF3AB is tuned somewhat differently from homodimeric processive kinesins. PMID- 25122756 TI - A novel eliminase from a marine bacterium that degrades hyaluronan and chondroitin sulfate. AB - Lyases cleave glycosaminoglycans (GAGs) in an eliminative mechanism and are important tools for the structural analysis and oligosaccharide preparation of GAGs. Various GAG lyases have been identified from terrestrial but not marine organisms even though marine animals are rich in GAGs with unique structures and functions. Herein we isolated a novel GAG lyase for the first time from the marine bacterium Vibrio sp. FC509 and then recombinantly expressed and characterized it. It showed strong lyase activity toward hyaluronan (HA) and chondroitin sulfate (CS) and was designated as HA and CS lyase (HCLase). It exhibited the highest activities to both substrates at pH 8.0 and 0.5 m NaCl at 30 degrees C. Its activity toward HA was less sensitive to pH than its CS lyase activity. As with most other marine enzymes, HCLase is a halophilic enzyme and very stable at temperatures from 0 to 40 degrees C for up to 24 h, but its activity is independent of divalent metal ions. The specific activity of HCLase against HA and CS reached a markedly high level of hundreds of thousands units/mg of protein under optimum conditions. The HCLase-resistant tetrasaccharide Delta(4,5)HexUAalpha1-3GalNAc(6-O-sulfate)beta1-4GlcUA(2-O-sulfate)beta1 3GalNAc(6-O-sulfate) was isolated from CS-D, the structure of which indicated that HCLase could not cleave the galactosaminidic linkage bound to 2-O-sulfated d glucuronic acid (GlcUA) in CS chains. Site-directed mutagenesis indicated that HCLase may work via a catalytic mechanism in which Tyr-His acts as the Bronsted base and acid. Thus, the identification of HCLase provides a useful tool for HA- and CS-related research and applications. PMID- 25122757 TI - The atomic resolution structure of human AlkB homolog 7 (ALKBH7), a key protein for programmed necrosis and fat metabolism. AB - ALKBH7 is the mitochondrial AlkB family member that is required for alkylation- and oxidation-induced programmed necrosis. In contrast to the protective role of other AlkB family members after suffering alkylation-induced DNA damage, ALKBH7 triggers the collapse of mitochondrial membrane potential and promotes cell death. Moreover, genetic ablation of mouse Alkbh7 dramatically increases body weight and fat mass. Here, we present crystal structures of human ALKBH7 in complex with Mn(II) and alpha-ketoglutarate at 1.35 A or N-oxalylglycine at 2.0 A resolution. ALKBH7 possesses the conserved double-stranded beta-helix fold that coordinates a catalytically active iron by a conserved HX(D/E) ... Xn ... H motif. Self-hydroxylation of Leu-110 was observed, indicating that ALKBH7 has the potential to catalyze hydroxylation of its substrate. Unlike other AlkB family members whose substrates are DNA or RNA, ALKBH7 is devoid of the "nucleotide recognition lid" which is essential for binding nucleobases, and thus exhibits a solvent-exposed active site; two loops between beta-strands beta6 and beta7 and between beta9 and beta10 create a special outer wall of the minor beta-sheet of the double-stranded beta-helix and form a negatively charged groove. These distinct features suggest that ALKBH7 may act on protein substrate rather than nucleic acids. Taken together, our findings provide a structural basis for understanding the distinct function of ALKBH7 in the AlkB family and offer a foundation for drug design in treating cell death-related diseases and metabolic diseases. PMID- 25122758 TI - Electrostatic interactions in the binding pathway of a transient protein complex studied by NMR and isothermal titration calorimetry. AB - Much of our knowledge of protein binding pathways is derived from extremely stable complexes that interact very tightly, with lifetimes of hours to days. Much less is known about weaker interactions and transient complexes because these are challenging to characterize experimentally. Nevertheless, these types of interactions are ubiquitous in living systems. The combination of NMR relaxation dispersion Carr-Purcell-Meiboom-Gill (CPMG) experiments and isothermal titration calorimetry allows the quantification of rapid binding kinetics for complexes with submillisecond lifetimes that are difficult to study using conventional techniques. We have used this approach to investigate the binding pathway of the Src homology 3 (SH3) domain from the Fyn tyrosine kinase, which forms complexes with peptide targets whose lifetimes are on the order of about a millisecond. Long range electrostatic interactions have been shown to play a critical role in the binding pathways of tightly binding complexes. The role of electrostatics in the binding pathways of transient complexes is less well understood. Similarly to previously studied tight complexes, we find that SH3 domain association rates are enhanced by long range electrostatics, whereas short range interactions are formed late in the docking process. However, the extent of electrostatic association rate enhancement is several orders of magnitudes less, whereas the electrostatic-free basal association rate is significantly greater. Thus, the SH3 domain is far less reliant on electrostatic enhancement to achieve rapid association kinetics than are previously studied systems. This suggests that there may be overall differences in the role played by electrostatics in the binding pathways of extremely stable versus transient complexes. PMID- 25122759 TI - Stable single alpha-helices are constant force springs in proteins. AB - Single alpha-helix (SAH) domains are rich in charged residues (Arg, Lys, and Glu) and stable in solution over a wide range of pH and salt concentrations. They are found in many different proteins where they bridge two functional domains. To test the idea that their high stability might enable these proteins to resist unfolding along their length, the properties and unfolding behavior of the predicted SAH domain from myosin-10 were characterized. The expressed and purified SAH domain was highly helical, melted non-cooperatively, and was monomeric as shown by circular dichroism and mass spectrometry as expected for a SAH domain. Single molecule force spectroscopy experiments showed that the SAH domain unfolded at very low forces (<30 pN) without a characteristic unfolding peak. Molecular dynamics simulations showed that the SAH domain unfolds progressively as the length is increased and refolds progressively as the length is reduced. This enables the SAH domain to act as a constant force spring in the mechanically dynamic environment of the cell. PMID- 25122760 TI - Activating transcription factor 3-mediated chemo-intervention with cancer chemokines in a noncanonical pathway under endoplasmic reticulum stress. AB - The cell-protective features of the endoplasmic reticulum (ER) stress response are chronically activated in vigorously growing malignant tumor cells, which provide cellular growth advantages over the adverse microenvironment including chemotherapy. As an intervention with ER stress responses in the intestinal cancer cells, preventive exposure to flavone apigenin potentiated superinduction of a regulatory transcription factor, activating transcription factor 3 (ATF3), which is also known to be an integral player coordinating ER stress response related gene expression. ATF3 superinduction was due to increased turnover of ATF3 transcript via stabilization with HuR protein in the cancer cells under ER stress. Moreover, enhanced ATF3 caused inhibitory action against ER stress induced cancer chemokines that are potent mediators determining the survival and metastatic potential of epithelial cancer cells. Although enhanced ATF3 was a negative regulator of the well known proinflammatory transcription factor NF kappaB, blocking of NF-kappaB signaling did not affect ER stress-induced chemokine expression. Instead, immediately expressed transcription factor early growth response protein 1 (EGR-1) was positively involved in cancer chemokine induction by ER stressors. ER stress-induced EGR-1 and subsequent chemokine production were repressed by ATF3. Mechanistically, ATF3 directly interacted with and recruited HDAC1 protein, which led to epigenetic suppression of EGR-1 expression and subsequent chemokine production. Conclusively, superinduced ATF3 attenuated ER stress-induced cancer chemokine expression by epigenetically interfering with induction of EGR-1, a transcriptional modulator crucial to cancer chemokine production. Thus, these results suggest a potent therapeutic intervention of ER stress response-related cancer-favoring events by ATF3. PMID- 25122761 TI - Group X secretory phospholipase A2 regulates insulin secretion through a cyclooxygenase-2-dependent mechanism. AB - Group X secretory phospholipase A2 (GX sPLA2) potently hydrolyzes membrane phospholipids to release arachidonic acid (AA). While AA is an activator of glucose-stimulated insulin secretion (GSIS), its metabolite prostaglandin E2 (PGE2) is a known inhibitor. In this study, we determined that GX sPLA2 is expressed in insulin-producing cells of mouse pancreatic islets and investigated its role in beta cell function. GSIS was measured in vivo in wild-type (WT) and GX sPLA2-deficient (GX KO) mice and ex vivo using pancreatic islets isolated from WT and GX KO mice. GSIS was also assessed in vitro using mouse MIN6 pancreatic beta cells with or without GX sPLA2 overexpression or exogenous addition. GSIS was significantly higher in islets isolated from GX KO mice compared with islets from WT mice. Conversely, GSIS was lower in MIN6 cells overexpressing GX sPLA2 (MIN6-GX) compared with control (MIN6-C) cells. PGE2 production was significantly higher in MIN6-GX cells compared with MIN6-C cells and this was associated with significantly reduced cellular cAMP. The effect of GX sPLA2 on GSIS was abolished when cells were treated with NS398 (a COX-2 inhibitor) or L-798,106 (a PGE2-EP3 receptor antagonist). Consistent with enhanced beta cell function, GX KO mice showed significantly increased plasma insulin levels following glucose challenge and were protected from age-related reductions in GSIS and glucose tolerance compared with WT mice. We conclude that GX sPLA2 plays a previously unrecognized role in negatively regulating pancreatic insulin secretion by augmenting COX-2 dependent PGE2 production. PMID- 25122762 TI - Peroxiredoxin 4 improves insulin biosynthesis and glucose-induced insulin secretion in insulin-secreting INS-1E cells. AB - Oxidative folding of (pro)insulin is crucial for its assembly and biological function. This process takes place in the endoplasmic reticulum (ER) and is accomplished by protein disulfide isomerase and ER oxidoreductin 1beta, generating stoichiometric amounts of hydrogen peroxide (H2O2) as byproduct. During insulin resistance in the prediabetic state, increased insulin biosynthesis can overwhelm the ER antioxidative and folding capacity, causing an imbalance in the ER redox homeostasis and oxidative stress. Peroxiredoxin 4 (Prdx4), an ER-specific antioxidative peroxidase can utilize luminal H2O2 as driving force for reoxidizing protein disulfide isomerase family members, thus efficiently contributing to disulfide bond formation. Here, we examined the functional significance of Prdx4 on beta-cell function with emphasis on insulin content and secretion during stimulation with nutrient secretagogues. Overexpression of Prdx4 in glucose-responsive insulin-secreting INS-1E cells significantly metabolized luminal H2O2 and improved the glucose-induced insulin secretion, which was accompanied by the enhanced proinsulin mRNA transcription and insulin content. This beta-cell beneficial effect was also observed upon stimulation with the nutrient insulin secretagogue combination of leucine plus glutamine, indicating that the effect is not restricted to glucose. However, knockdown of Prdx4 had no impact on H2O2 metabolism or beta-cell function due to the fact that Prdx4 expression is negligibly low in pancreatic beta-cells. Moreover, we provide evidence that the constitutively low expression of Prdx4 is highly susceptible to hyperoxidation in the presence of high glucose. Overall, these data suggest an important role of Prdx4 in maintaining insulin levels and improving the ER folding capacity also under conditions of a high insulin requirement. PMID- 25122763 TI - Heat shock protein 83 (Hsp83) facilitates methoprene-tolerant (Met) nuclear import to modulate juvenile hormone signaling. AB - Juvenile hormone (JH) receptors, methoprene-tolerant (Met) and Germ-cell expressed (Gce), transduce JH signals to induce Kr-h1 expression in Drosophila. Dual luciferase assay identified a 120-bp JH response region (JHRR) in the Kr h1alpha promoter. Both in vitro and in vivo experiments revealed that Met and Gce transduce JH signals to induce Kr-h1 expression through the JHRR. DNA affinity purification identified chaperone protein Hsp83 as one of the proteins bound to the JHRR in the presence of JH. Interestingly, Hsp83 physically interacts with PAS-B and basic helix-loop-helix domains of Met, and JH induces Met-Hsp83 interaction. As determined by immunohistochemistry, Met is mainly distributed in the cytoplasm of fat body cells of the larval when the JH titer is low and JH induces Met nuclear import. Hsp83 was accumulated in the cytoplasm area adjunct to the nucleus in the presence of JH and Met/Gce. Loss-of-function of Hsp83 attenuated JH binding and JH-induced nuclear import of Met, resulting in a decrease in the JHRR-driven reporter activity leading to reduction of Kr-h1 expression. These data show that Hsp83 facilitates the JH-induced nuclear import of Met that induces Kr-h1 expression through the JHRR. PMID- 25122764 TI - A pituitary homeobox 2 (Pitx2):microRNA-200a-3p:beta-catenin pathway converts mesenchymal cells to amelogenin-expressing dental epithelial cells. AB - Pitx2, Wnt/beta-catenin signaling, and microRNAs (miRs) play a critical role in the regulation of dental stem cells during embryonic development. In this report, we have identified a Pitx2:beta-catenin regulatory pathway involved in epithelial cell differentiation and conversion of mesenchymal cells to amelogenin expressing epithelial cells via miR-200a. Pitx2 and beta-catenin are expressed in the labial incisor cervical loop or epithelial stem cell niche, with decreased expression in the differentiating ameloblast cells of the mouse lower incisor. Bioinformatics analyses reveal that miR-200a-3p expression is activated in the pre-ameloblast cells to enhance epithelial cell differentiation. We demonstrate that Pitx2 activates miR-200a-3p expression and miR-200a-3p reciprocally represses Pitx2 and beta-catenin expression. Pitx2 and beta-catenin interact to synergistically activate gene expression during odontogenesis and miR-200a-3p attenuates their expression and directs differentiation. To understand how this mechanism controls cell differentiation and cell fate, oral epithelial and odontoblast mesenchymal cells were reprogrammed by a two-step induction method using Pitx2 and miR-200a 3p. Conversion to amelogenin expressing dental epithelial cells involved an up regulation of the stem cell marker Sox2 and proliferation genes and decreased expression of mesenchymal markers. E-cadherin expression was increased as well as ameloblast specific factors. The combination of Pitx2, a regulator of dental stem cells and miR-200a converts mesenchymal cells to a fully differentiated dental epithelial cell type. This pathway and reprogramming can be used to reprogram mesenchymal or oral epithelial cells to dental epithelial (ameloblast) cells, which can be used in tissue repair and regeneration studies. PMID- 25122765 TI - Determinants of versican-V1 proteoglycan processing by the metalloproteinase ADAMTS5. AB - Proteolysis of the Glu(441)-Ala(442) bond in the glycosaminoglycan (GAG) beta domain of the versican-V1 variant by a disintegrin-like and metalloproteinase domain with thrombospondin type 1 motif (ADAMTS) proteases is required for proper embryo morphogenesis. However, the processing mechanism and the possibility of additional ADAMTS-cleaved processing sites are unknown. We demonstrate here that if Glu(441) is mutated, ADAMTS5 cleaves inefficiently at a proximate upstream site but normally does not cleave elsewhere within the GAGbeta domain. Chondroitin sulfate (CS) modification of versican is a prerequisite for cleavage at the Glu(441)-Ala(442) site, as demonstrated by reduced processing of CS deficient or chondroitinase ABC-treated versican-V1. Site-directed mutagenesis identified the N-terminal CS attachment sites Ser(507) and Ser(525) as essential for processing of the Glu(441)-Ala(442) bond by ADAMTS5. A construct including only these two GAG chains, but not downstream GAG attachment sites, was cleaved efficiently. Therefore, CS chain attachment to Ser(507) and Ser(525) is necessary and sufficient for versican proteolysis by ADAMTS5. Mutagenesis of Glu(441) and an antibody to a peptide spanning Thr(432)-Gly(445) (i.e. containing the scissile bond) reduced versican-V1 processing. ADAMTS5 lacking the C-terminal ancillary domain did not cleave versican, and an ADAMTS5 ancillary domain construct bound versican-V1 via the CS chains. We conclude that docking of ADAMTS5 with two N terminal GAG chains of versican-V1 via its ancillary domain is required for versican processing at Glu(441)-Ala(442). V1 proteolysis by ADAMTS1 demonstrated a similar requirement for the N-terminal GAG chains and Glu(441). Therefore, versican cleavage can be inhibited substantially by mutation of Glu(441), Ser(507), and Ser(525) or by an antibody to the region of the scissile bond. PMID- 25122766 TI - Myosin light chain kinase (MLCK) regulates cell migration in a myosin regulatory light chain phosphorylation-independent mechanism. AB - Myosin light chain kinase (MLCK) has long been implicated in the myosin phosphorylation and force generation required for cell migration. Here, we surprisingly found that the deletion of MLCK resulted in fast cell migration, enhanced protrusion formation, and no alteration of myosin light chain phosphorylation. The mutant cells showed reduced membrane tether force and fewer membrane F-actin filaments. This phenotype was rescued by either kinase-dead MLCK or five-DFRXXL motif, a MLCK fragment with potent F-actin-binding activity. Pull down and co-immunoprecipitation assays showed that the absence of MLCK led to attenuated formation of transmembrane complexes, including myosin II, integrins and fibronectin. We suggest that MLCK is not required for myosin phosphorylation in a migrating cell. A critical role of MLCK in cell migration involves regulating the cell membrane tension and protrusion necessary for migration, thereby stabilizing the membrane skeleton through F-actin-binding activity. This finding sheds light on a novel regulatory mechanism of protrusion during cell migration. PMID- 25122767 TI - Hyaluronan breakdown contributes to immune defense against group A Streptococcus. AB - Group A Streptococcus (GAS) commonly infects human skin and occasionally causes severe and life-threatening invasive diseases. The hyaluronan (HA) capsule of GAS has been proposed to protect GAS from host defense by mimicking endogenous HA, a large and abundant glycosaminoglycan in the skin. However, HA is degraded during tissue injury, and the functions of short-chain HA that is generated during infection have not been studied. To examine the impact of the molecular mass of HA on GAS infection, we established infection models in vitro and in vivo in which the size of HA was defined by enzymatic digestion or custom synthesis. We discovered that conversion of high molecular mass HA to low molecular mass HA facilitated GAS phagocytosis by macrophages and limited the severity of infection in mice. In contrast, native high molecular mass HA significantly impaired internalization by macrophages and increased GAS survival in murine blood. Thus, our data demonstrate that GAS virulence can be influenced by the size of HA derived from both the bacterium and host and suggest that high molecular mass HA facilitates GAS deep tissue infections, whereas the generation of short-chain HA can be protective. PMID- 25122768 TI - Thiosulfate transfer mediated by DsrE/TusA homologs from acidothermophilic sulfur oxidizing archaeon Metallosphaera cuprina. AB - Conserved clusters of genes encoding DsrE and TusA homologs occur in many archaeal and bacterial sulfur oxidizers. TusA has a well documented function as a sulfurtransferase in tRNA modification and molybdenum cofactor biosynthesis in Escherichia coli, and DsrE is an active site subunit of the DsrEFH complex that is essential for sulfur trafficking in the phototrophic sulfur-oxidizing Allochromatium vinosum. In the acidothermophilic sulfur (S(0))- and tetrathionate (S4O6(2-))-oxidizing Metallosphaera cuprina Ar-4, a dsrE3A-dsrE2B-tusA arrangement is situated immediately between genes encoding dihydrolipoamide dehydrogenase and a heterodisulfide reductase-like complex. In this study, the biochemical features and sulfur transferring abilities of the DsrE2B, DsrE3A, and TusA proteins were investigated. DsrE3A and TusA proved to react with tetrathionate but not with NaSH, glutathione persulfide, polysulfide, thiosulfate, or sulfite. The products were identified as protein-Cys-S thiosulfonates. DsrE3A was also able to cleave the thiosulfate group from TusA Cys(18)-S-thiosulfonate. DsrE2B did not react with any of the sulfur compounds tested. DsrE3A and TusA interacted physically with each other and formed a heterocomplex. The cysteine residue (Cys(18)) of TusA is crucial for this interaction. The single cysteine mutants DsrE3A-C(93)S and DsrE3A-C(101)S retained the ability to transfer the thiosulfonate group to TusA. TusA-C(18)S neither reacted with tetrathionate nor was it loaded with thiosulfate with DsrE3A Cys-S-thiosulfonate as the donor. The transfer of thiosulfate, mediated by a DsrE like protein and TusA, is unprecedented not only in M. cuprina but also in other sulfur-oxidizing prokaryotes. The results of this study provide new knowledge on oxidative microbial sulfur metabolism. PMID- 25122769 TI - Mitogen-activated protein kinase (MAPK)-regulated interactions between Osterix and Runx2 are critical for the transcriptional osteogenic program. AB - The transcription factors Runx2 and Osx (Osterix) are required for osteoblast differentiation and bone formation. Runx2 expression occurs at early stages of osteochondroprogenitor determination, followed by Osx induction during osteoblast maturation. We demonstrate that coexpression of Osx and Runx2 leads to cooperative induction of expression of the osteogenic genes Col1a1, Fmod, and Ibsp. Functional interaction of Osx and Runx2 in the regulation of these promoters is mediated by enhancer regions with adjacent Sp1 and Runx2 DNA-binding sites. These enhancers allow formation of a cooperative transcriptional complex, mediated by the binding of Osx and Runx2 to their specific DNA promoter sequences and by the protein-protein interactions between them. We also identified the domains involved in the interaction between Osx and Runx2. These regions contain the amino acids in Osx and Runx2 known to be phosphorylated by p38 and ERK MAPKs. Inhibition of p38 and ERK kinase activities or mutation of their known phosphorylation sites in Osx or Runx2 strongly disrupts their physical interaction and cooperative transcriptional effects. Altogether, our results provide a molecular description of a mechanism for Osx and Runx2 transcriptional cooperation that is subject to further regulation by MAPK-activating signals during osteogenesis. PMID- 25122771 TI - A distinct switch in interactions of the histone H4 tail domain upon salt dependent folding of nucleosome arrays. AB - The core histone tail domains mediate inter-nucleosomal interactions that direct folding and condensation of nucleosome arrays into higher-order chromatin structures. The histone H4 tail domain facilitates inter-array interactions by contacting both the H2A/H2B acidic patch and DNA of neighboring nucleosomes. Likewise, H4 tail-H2A contacts stabilize array folding. However, whether the H4 tail domains stabilize array folding via inter-nucleosomal interactions with the DNA of neighboring nucleosomes remains unclear. We utilized defined oligonucleosome arrays containing a single specialized nucleosome with a photo inducible cross-linker in the N terminus of the H4 tail to characterize these interactions. We observed that the H4 tail participates exclusively in intra array interactions with DNA in unfolded arrays. These interactions are diminished during array folding, yet no inter-nucleosome, intra-array H4 tail-DNA contacts are observed in condensed chromatin. However, we document contacts between the N terminus of the H4 tail and H2A. Installation of acetylation mimics known to disrupt H4-H2A surface interactions did not increase observance of H4-DNA inter nucleosomal interactions. These results suggest the multiple functions of the H4 tail require targeted distinct interactions within condensed chromatin. PMID- 25122770 TI - Interaction with the Src homology (SH3-SH2) region of the Src-family kinase Hck structures the HIV-1 Nef dimer for kinase activation and effector recruitment. AB - HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 A. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu 93 interfered with Nef.Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners. PMID- 25122772 TI - Inhibition of neuronal cell mitochondrial complex I with rotenone increases lipid beta-oxidation, supporting acetyl-coenzyme A levels. AB - Rotenone is a naturally occurring mitochondrial complex I inhibitor with a known association with parkinsonian phenotypes in both human populations and rodent models. Despite these findings, a clear mechanistic link between rotenone exposure and neuronal damage remains to be determined. Here, we report alterations to lipid metabolism in SH-SY5Y neuroblastoma cells exposed to rotenone. The absolute levels of acetyl-CoA were found to be maintained despite a significant decrease in glucose-derived acetyl-CoA. Furthermore, palmitoyl-CoA levels were maintained, whereas the levels of many of the medium-chain acyl-CoA species were significantly reduced. Additionally, using isotopologue analysis, we found that beta-oxidation of fatty acids with varying chain lengths helped maintain acetyl-CoA levels. Rotenone also induced increased glutamine utilization for lipogenesis, in part through reductive carboxylation, as has been found previously in other cell types. Finally, palmitoylcarnitine levels were increased in response to rotenone, indicating an increase in fatty acid import. Taken together, these findings show that alterations to lipid and glutamine metabolism play an important compensatory role in response to complex I inhibition by rotenone. PMID- 25122773 TI - Inhibition of the functional interplay between endoplasmic reticulum (ER) oxidoreduclin-1alpha (Ero1alpha) and protein-disulfide isomerase (PDI) by the endocrine disruptor bisphenol A. AB - Bisphenol A (BPA) is an endocrine disruptor that may have adverse effects on human health. We recently isolated protein-disulfide isomerase (PDI) as a BPA binding protein from rat brain homogenates and found that BPA markedly inhibited PDI activity. To elucidate mechanisms of this inhibition, detailed structural, biophysical, and functional analyses of PDI were performed in the presence of BPA. BPA binding to PDI induced significant rearrangement of the N-terminal thioredoxin domain of PDI, resulting in more compact overall structure. This conformational change led to closure of the substrate-binding pocket in b' domain, preventing PDI from binding to unfolded proteins. The b' domain also plays an essential role in the interplay between PDI and ER oxidoreduclin 1alpha (Ero1alpha), a flavoenzyme responsible for reoxidation of PDI. We show that BPA inhibited Ero1alpha-catalyzed PDI oxidation presumably by inhibiting the interaction between the b' domain of PDI and Ero1alpha; the phenol groups of BPA probably compete with a highly conserved tryptophan residue, located in the protruding beta-hairpin of Ero1alpha, for binding to PDI. Consistently, BPA slowed down the reoxidation of PDI and caused the reduction of PDI in HeLa cells, indicating that BPA has a great impact on the redox homeostasis of PDI within cells. However, BPA had no effect on the interaction between PDI and peroxiredoxin-4 (Prx4), another PDI family oxidase, suggesting that the interaction between Prx4 and PDI is different from that of Ero1alpha and PDI. These results indicate that BPA, a widely distributed and potentially harmful chemical, inhibits Ero1-PDI-mediated disulfide bond formation. PMID- 25122775 TI - HIV vaccine trial exploits a dual and central role for innate immunity. AB - Limited understanding of correlates of protection from HIV transmission hinders development of an efficacious vaccine. D. J. M. Lewis and colleagues (J. Virol. 88:11648-11657, 2014, doi:10.1128/JVI.01621-14) now report that vaginal immunization with an HIVgp140 vaccine linked to the 70-kDa heat shock protein downregulated the human immunodeficiency virus (HIV) coreceptor CCR5 (chemokine [C-C motif] receptor 5) and increased expression of the HIV resistance factor APOBEC3G (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G), in women. These effects correlated with HIV suppression ex vivo. Thus, vaccine induced innate responses not only facilitate adaptive immunity-they may prove to be critical for preventing HIV transmission. PMID- 25122774 TI - 3,6,2',4',5'-Pentahydroxyflavone, an orally bioavailable multiple protein kinase inhibitor, overcomes gefitinib resistance in non-small cell lung cancer. AB - Non-small cell lung cancer (NSCLC) is the most lethal cancer, causing more than 150,000 deaths in the United States in 2013. The receptor tyrosine kinase inhibitors such as gefitinib are not perfect clinical therapeutic agents for NSCLC treatment due to primary or acquired tyrosine kinase inhibitor resistance. Herein, 3,6,2',4',5'-pentahydroxyflavone (36245-PHF) was identified as a multiple kinase inhibitor for NSCLC treatment based on the computational screening of a natural products database. 36245-PHF was shown to inhibit PI3K and Aurora A and B kinases and overcome gefitinib-resistant NSCLC growth. Our data clearly showed that 36245-PHF markedly inhibited anchorage-independent growth of gefitinib resistant NSCLC cell lines and exerted a substantial chemotherapeutic effect following oral administration in a gefitinib-resistant NSCLC xenograft model. The evidence from three different subsequent methodological approaches, in vitro, ex vivo, and in vivo, all confirmed that 36245-PHF as a multiple protein kinase inhibitor. Overall, we identified 36245-PHF as a multiple protein kinase inhibitor and as a novel therapeutic agent to overcome gefitinib-resistant NSCLC growth, which could provide a new option for clinical NSCLC oral treatment. PMID- 25122777 TI - Type I interferon protects mice from fatal neurotropic infection with Langat virus by systemic and local antiviral responses. AB - Vector-borne flaviviruses, such as tick-borne encephalitis virus (TBEV), West Nile virus, and dengue virus, cause millions of infections in humans. TBEV causes a broad range of pathological symptoms, ranging from meningitis to severe encephalitis or even hemorrhagic fever, with high mortality. Despite the availability of an effective vaccine, the incidence of TBEV infections is increasing. Not much is known about the role of the innate immune system in the control of TBEV infections. Here, we show that the type I interferon (IFN) system is essential for protection against TBEV and Langat virus (LGTV) in mice. In the absence of a functional IFN system, mice rapidly develop neurological symptoms and succumb to LGTV and TBEV infections. Type I IFN system deficiency results in severe neuroinflammation in LGTV-infected mice, characterized by breakdown of the blood-brain barrier and infiltration of macrophages into the central nervous system (CNS). Using mice with tissue-specific IFN receptor deletions, we show that coordinated activation of the type I IFN system in peripheral tissues as well as in the CNS is indispensable for viral control and protection against virus induced inflammation and fatal encephalitis. IMPORTANCE: The type I interferon (IFN) system is important to control viral infections; however, the interactions between tick-borne encephalitis virus (TBEV) and the type I IFN system are poorly characterized. TBEV causes severe infections in humans that are characterized by fever and debilitating encephalitis, which can progress to chronic illness or death. No treatment options are available. An improved understanding of antiviral innate immune responses is pivotal for the development of effective therapeutics. We show that type I IFN, an effector molecule of the innate immune system, is responsible for the extended survival of TBEV and Langat virus (LGTV), an attenuated member of the TBE serogroup. IFN production and signaling appeared to be essential in two different phases during infection. The first phase is in the periphery, by reducing systemic LGTV replication and spreading into the central nervous system (CNS). In the second phase, the local IFN response in the CNS prevents virus-induced inflammation and the development of encephalitis. PMID- 25122776 TI - Increased replicative fitness can lead to decreased drug sensitivity of hepatitis C virus. AB - Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-alpha), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV. Importance: Viral drug resistance is usually attributed to the presence of amino acid substitutions in the protein targeted by the drug. In the present study with HCV, we show that high viral replicative fitness can confer a general drug resistance phenotype to the virus. The results exclude the possibility that genomes with drug resistance mutations are responsible for the observed phenotype. The fact that replicative fitness can be a determinant of multidrug resistance may explain why the virus is less sensitive to drug treatments in prolonged chronic HCV infections that favor increases in replicative fitness. PMID- 25122778 TI - Computational prediction of vaccine strains for human influenza A (H3N2) viruses. AB - Human influenza A viruses are rapidly evolving pathogens that cause substantial morbidity and mortality in seasonal epidemics around the globe. To ensure continued protection, the strains used for the production of the seasonal influenza vaccine have to be regularly updated, which involves data collection and analysis by numerous experts worldwide. Computer-guided analysis is becoming increasingly important in this problem due to the vast amounts of generated data. We here describe a computational method for selecting a suitable strain for production of the human influenza A virus vaccine. It interprets available antigenic and genomic sequence data based on measures of antigenic novelty and rate of propagation of the viral strains throughout the population. For viral isolates sampled between 2002 and 2007, we used this method to predict the antigenic evolution of the H3N2 viruses in retrospective testing scenarios. When seasons were scored as true or false predictions, our method returned six true positives, three false negatives, eight true negatives, and one false positive, or 78% accuracy overall. In comparison to the recommendations by the WHO, we identified the correct antigenic variant once at the same time and twice one season ahead. Even though it cannot be ruled out that practical reasons such as lack of a sufficiently well-growing candidate strain may in some cases have prevented recommendation of the best-matching strain by the WHO, our computational decision procedure allows quantitative interpretation of the growing amounts of data and may help to match the vaccine better to predominating strains in seasonal influenza epidemics. Importance: Human influenza A viruses continuously change antigenically to circumvent the immune protection evoked by vaccination or previously circulating viral strains. To maintain vaccine protection and thereby reduce the mortality and morbidity caused by infections, regular updates of the vaccine strains are required. We have developed a data driven framework for vaccine strain prediction which facilitates the computational analysis of genetic and antigenic data and does not rely on explicit evolutionary models. Our computational decision procedure generated good matches of the vaccine strain to the circulating predominant strain for most seasons and could be used to support the expert-guided prediction made by the WHO; it thus may allow an increase in vaccine efficacy. PMID- 25122780 TI - Core-binding factor subunit beta is not required for non-primate lentiviral Vif mediated APOBEC3 degradation. AB - Viral infectivity factor (Vif) is required for lentivirus fitness and pathogenicity, except in equine infectious anemia virus (EIAV). Vif enhances viral infectivity by a Cullin5-Elongin B/C E3 complex to inactivate the host restriction factor APOBEC3. Core-binding factor subunit beta (CBF-beta) is a cell factor that was recently shown to be important for the primate lentiviral Vif function. Non-primate lentiviral Vif also degrades APOBEC3 through the proteasome pathway. However, it is unclear whether CBF-beta is required for the non-primate lentiviral Vif function. In this study, we demonstrated that the Vifs of non primate lentiviruses, including feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), caprine arthritis encephalitis virus (CAEV), and maedi-visna virus (MVV), do not interact with CBF-beta. In addition, CBF-beta did not promote the stability of FIV, BIV, CAEV, and MVV Vifs. Furthermore, CBF-beta silencing or overexpression did not affect non-primate lentiviral Vif-mediated APOBEC3 degradation. Our results suggest that non-primate lentiviral Vif induces APOBEC3 degradation through a different mechanism than primate lentiviral Vif. Importance: The APOBEC3 protein family members are host restriction factors that block retrovirus replication. Vif, an accessory protein of lentivirus, degrades APOBEC3 to rescue viral infectivity by forming Cullin5-Elongin B/C-based E3 complex. CBF-beta was proved to be a novel regulator of primate lentiviral Vif function. In this study, we found that CBF-beta knockdown or overexpression did not affect FIV Vif's function, which induced polyubiquitination and degradation of APOBEC3 by recruiting the E3 complex in a manner similar to that of HIV-1 Vif. We also showed that other non-primate lentiviral Vifs did not require CBF-beta to degrade APOBEC3. CBF-beta did not interact with non-primate lentiviral Vifs or promote their stability. These results suggest that a different mechanism exists for the Vif-APOBEC interaction and that non-primates are not suitable animal models for exploring pharmacological interventions that disrupt Vif-CBF-beta interaction. PMID- 25122779 TI - Modulation of hepatitis C virus genome replication by glycosphingolipids and four phosphate adaptor protein 2. AB - Hepatitis C virus (HCV) assembles its replication complex on cytosolic membrane vesicles often clustered in a membranous web (MW). During infection, HCV NS5A protein activates PI4KIIIalpha enzyme, causing massive production and redistribution of phosphatidylinositol 4-phosphate (PI4P) lipid to the replication complex. However, the role of PI4P in the HCV life cycle is not well understood. We postulated that PI4P recruits host effectors to modulate HCV genome replication or virus particle production. To test this hypothesis, we generated cell lines for doxycycline-inducible expression of short hairpin RNAs (shRNAs) targeting the PI4P effector, four-phosphate adaptor protein 2 (FAPP2). FAPP2 depletion attenuated HCV infectivity and impeded HCV RNA synthesis. Indeed, FAPP2 has two functional lipid-binding domains specific for PI4P and glycosphingolipids. While expression of the PI4P-binding mutant protein was expected to inhibit HCV replication, a marked drop in replication efficiency was observed unexpectedly with the glycosphingolipid-binding mutant protein. These data suggest that both domains are crucial for the role of FAPP2 in HCV genome replication. We also found that HCV significantly increases the level of some glycosphingolipids, whereas adding these lipids to FAPP2-depleted cells partially rescued replication, further arguing for the importance of glycosphingolipids in HCV RNA synthesis. Interestingly, FAPP2 is redistributed to the replication complex (RC) characterized by HCV NS5A, NS4B, or double-stranded RNA (dsRNA) foci. Additionally, FAPP2 depletion disrupts the RC and alters the colocalization of HCV replicase proteins. Altogether, our study implies that HCV coopts FAPP2 for virus genome replication via PI4P binding and glycosphingolipid transport to the HCV RC. IMPORTANCE: Like most viruses with a positive-sense RNA genome, HCV replicates its RNA on remodeled host membranes composed of lipids hijacked from various internal membrane compartments. During infection, HCV induces massive production and retargeting of the PI4P lipid to its replication complex. However, the role of PI4P in HCV replication is not well understood. In this study, we have shown that FAPP2, a PI4P effector and glycosphingolipid-binding protein, is recruited to the HCV replication complex and is required for HCV genome replication and replication complex formation. More importantly, this study demonstrates, for the first time, the crucial role of glycosphingolipids in the HCV life cycle and suggests a link between PI4P and glycosphingolipids in HCV genome replication. PMID- 25122781 TI - Emergence of broadly neutralizing antibodies and viral coevolution in two subjects during the early stages of infection with human immunodeficiency virus type 1. AB - Delineating the key early events that lead to the development of broadly neutralizing anti-HIV-1 antibodies during natural infection may help guide the development of immunogens and vaccine regimens to prevent HIV-1 infection. In this study, we monitored two HIV-1-positive subjects, VC20013 and VC10014, over the course of infection from before they developed broadly neutralizing antibody (bNAb) activity until several years after neutralizing breadth was detected in plasma. Both subjects developed bNAb activity after approximately 1 year postinfection, which ultimately mapped to the membrane-proximal external region (MPER) in VC20013 and an epitope that overlaps the CD4 receptor binding site in VC10014. In subject VC20013, we were able to identify anti-MPER activity in the earliest plasma sample that exhibited no bNAb activity, indicating that this epitope specificity was acquired very early on, but that it was initially not able to mediate neutralization. Escape mutations within the bNAb epitopes did not arise in the circulating envelopes until bNAb activity was detectable in plasma, indicating that this early response was not sufficient to drive viral escape. As bNAb activity began to emerge in both subjects, we observed a simultaneous increase in autologous antienvelope antibody binding affinity, indicating that antibody maturation was occurring as breadth was developing. Our findings illustrate one potential mechanism by which bNAbs develop during natural infection in which an epitope target is acquired very early on during the course of infection but require time and maturation to develop into broadly neutralizing activity. IMPORTANCE: One major goal of HIV-1 vaccine research is the development of a vaccine that can elicit broadly neutralizing antibodies (bNAbs). Although no such vaccine exists, bNAbs develop in approximately 20% of HIV-1-infected subjects, providing a prototype of the bNAbs that must be reelicited by vaccine. Thus, there is significant interest in understanding the mechanisms by which bNAbs develop during the course of infection. We studied the timing, epitope specificity, and evolution of the bNAb responses in two HIV-1-positive patients who developed bNAb activity within the first several years after infection. In one subject, antibodies to a broadly neutralizing epitope developed very early but were nonneutralizing. After several months, neutralizing activity developed, and the virus mutated to escape their activity. Our study highlights one mechanism for the development of bNAbs where early epitope acquisition followed by sufficient time for antibody maturation drives the epitope-specific antibody response toward broadly neutralizing activity. PMID- 25122782 TI - Probing the functions of the paramyxovirus glycoproteins F and HN with a panel of synthetic antibodies. AB - Paramyxoviruses are enveloped negative-strand RNA viruses that are significant human and animal pathogens. Most paramyxoviruses infect host cells via the concerted action of a tetrameric attachment protein (variously called HN, H, or G) that binds either sialic acid or protein receptors on target cells and a trimeric fusion protein (F) that merges the viral envelope with the plasma membrane at neutral pH. F initially folds to a metastable prefusion conformation that becomes activated via a cleavage event during cellular trafficking. Upon receptor binding, the attachment protein, which consists of a globular head anchored to the membrane via a helical tetrameric stalk, triggers a major conformation change in F which results in fusion of virus and host cell membranes. We recently proposed a model for F activation in which the attachment protein head domains move following receptor binding to expose HN stalk residues critical for triggering F. To test the model in the context of wild-type viral glycoproteins, we used a restricted-diversity combinatorial Fab library and phage display to rapidly generate synthetic antibodies (sAbs) against multiple domains of the paramyxovirus parainfluenza 5 (PIV5) pre- and postfusion F and HN. As predicted by the model, sAbs that bind to the critical F-triggering region of the HN stalk do not disrupt receptor binding or neuraminidase (NA) activity but are potent inhibitors of fusion. An inhibitory prefusion F-specific sAb recognized a quaternary antigenic site and may inhibit fusion by preventing F refolding or by blocking the F-HN interaction. Importance: The paramyxovirus family of negative strand RNA viruses cause significant disease in humans and animals. The viruses bind to cells via their receptor binding protein and then enter cells by fusion of their envelope with the host cell plasma membrane, a process mediated by a metastable viral fusion (F) protein. To understand the steps in viral membrane fusion, a library of synthetic antibodies to F protein and the receptor binding protein was generated in bacteriophage. These antibodies bound to different regions of the F protein and the receptor binding protein, and the location of antibody binding affected different processes in viral entry into cells. PMID- 25122783 TI - Visualization of retroviral envelope spikes in complex with the V3 loop antibody 447-52D on intact viruses by cryo-electron tomography. AB - The gp120 portion of the envelope spike on human immunodeficiency virus type 1 (HIV-1) plays a critical role in viral entry into host cells and is a key target for the humoral immune response, and yet many structural details remain elusive. We have used cryoelectron tomography to visualize the binding of the broadly neutralizing monoclonal antibody (MAb) 447-52D to intact envelope spikes on virions of HIV-1 MN strain. Antibody 447-52D has previously been shown to bind to the tip of the V3 loop. Our results show antibody arms radiating from the sides of the gp120 protomers at a range of angles and place the antibody-bound V3 loop in an orientation that differs from that predicted by most current models but consistent with the idea that antibody binding dislodges the V3 loop from its location in the Env spike, making it flexible and disordered. These data reveal information on the position of the V3 loop and its relative flexibility and suggest that 447-52D neutralizes HIV-1 MN by capturing the V3 loop, blocking its interaction with the coreceptor and altering the structure of the envelope spike. IMPORTANCE: Antibody neutralization is one of the primary ways that the body fights infection with HIV. Because HIV is a highly mutable virus, the body must constantly produce new antibodies to counter new strains of HIV that the body itself is producing. Consequently, antibodies capable of neutralizing multiple HIV strains are comparatively few. An improved understanding of the mechanism of antibody neutralization might advance the development of immunogens. Most neutralizing antibodies target the Env glycoprotein spikes found on the virus surface. The broadly neutralizing antibody 447-52D targets the highly conserved beta-turn of variable loop 3 (V3) of gp120. The importance of V3 lies in its contribution to the coreceptor binding site on the target cell. We show here that 447-52D binding to V3 converts the Env conformation from closed to open and makes the V3 loop highly flexible, implying disruption of coreceptor binding and attachment to the target cell. PMID- 25122784 TI - Equine viperin restricts equine infectious anemia virus replication by inhibiting the production and/or release of viral Gag, Env, and receptor via distortion of the endoplasmic reticulum. AB - Viperin is an endoplasmic reticulum (ER)-associated multifunctional protein that regulates virus replication and possesses broad antiviral activity. In many cases, viperin interferes with the trafficking and budding of viral structural proteins by distorting the membrane transportation system. The lentivirus equine infectious anemia virus (EIAV) has been studied extensively. In this study, we examined the restrictive effect of equine viperin (eViperin) on EIAV replication and investigated the possible molecular basis of this restriction to obtain insights into the effect of this cellular factor on retroviruses. We demonstrated that EIAV infection of primary equine monocyte-derived macrophages (eMDMs) upregulated the expression of eViperin. The overexpression of eViperin significantly inhibited the replication of EIAV in eMDMs, and knockdown of eViperin transcription enhanced the replication of EIAV in eMDMs by approximately 45.8%. Further experiments indicated that eViperin restricts EIAV at multiple steps of viral replication. The overexpression of eViperin inhibited EIAV Gag release. Both the alpha-helix domain and radical S-adenosylmethionine (SAM) domain were required for this activity. However, the essential motifs in SAM were different from those reported for the inhibition of HIV-1 Gag by human viperin. Furthermore, eViperin disrupted the synthesis of both EIAV Env and receptor, which consequently inhibited viral production and entry, respectively, and this disruption was dependent on the eViperin alpha-helix domain. Using immunofluorescence assays and electron microscopy, we demonstrated that the alpha helix domain is responsible for the distortion of the endoplasmic reticulum (ER). Finally, EIAV did not exhibit counteracting eViperin at the protein level. IMPORTANCE: In previous studies, viperin was indicated as restricting virus replications primarily by the inhibition of virus budding. Here, we show that viperin may have multiple antiviral mechanisms, including the reduction of EIAV Gag budding and Env expression, and these activities are dependent on different viperin domains. We especially demonstrate that the overexpression of viperin inhibits EIAV entry by decreasing the level of virus receptor. Therefore, viperin restriction of viruses is determined largely by the dependence of virus on the cellular membrane transportation system. PMID- 25122785 TI - Cross-clade ultrasensitive PCR-based assays to measure HIV persistence in large cohort studies. AB - A small pool of infected cells persists in HIV-infected individuals receiving antiretroviral therapy (ART). Here, we developed ultrasensitive assays to precisely measure the frequency of cells harboring total HIV DNA, integrated HIV DNA, and two long terminal repeat (2-LTR) circles. These assays are performed on cell lysates, which circumvents the labor-intensive step of DNA extraction, and rely on the coquantification of each HIV molecular form together with CD3 gene sequences to precisely measure cell input. Using primary isolates from HIV subtypes A, B, C, D, and CRF01_A/E, we demonstrate that these assays can efficiently quantify low target copy numbers from diverse HIV subtypes. We further used these assays to measure total HIV DNA, integrated HIV DNA, and 2-LTR circles in CD4(+) T cells from HIV-infected subjects infected with subtype B. All samples obtained from ART-naive subjects were positive for the three HIV molecular forms (n = 15). Total HIV DNA, integrated HIV DNA, and 2-LTR circles were detected in, respectively, 100%, 94%, and 77% of the samples from individuals in which HIV was suppressed by ART. Higher levels of total HIV DNA and 2-LTR circles were detected in untreated subjects than individuals on ART (P = 0.0003 and P = 0.0004, respectively), while the frequency of CD4(+) T cells harboring integrated HIV DNA did not differ between the two groups. These results demonstrate that these novel assays have the ability to quantify very low levels of HIV DNA of multiple HIV subtypes without the need for nucleic acid extraction, making them well suited for the monitoring of viral persistence in large populations of HIV-infected individuals. IMPORTANCE: Since the discovery of viral reservoirs in HIV-infected subjects receiving suppressive ART, measuring the degree of viral persistence has been one of the greatest challenges in the field of HIV research. Here, we report the development and validation of ultrasensitive assays to measure HIV persistence in HIV-infected individuals from multiple geographical regions. These assays are relatively inexpensive, do not require DNA extraction, and can be completed in a single day. Therefore, they are perfectly adapted to monitor HIV persistence in large cohorts of HIV-infected individuals and, given their sensitivity, can be used to monitor the efficacy of therapeutic strategies aimed at interfering with HIV persistence after prolonged ART. PMID- 25122787 TI - The N terminus of the influenza B virus nucleoprotein is essential for virus viability, nuclear localization, and optimal transcription and replication of the viral genome. AB - The nucleoprotein (NP) of influenza viruses is a multifunctional protein with essential roles throughout viral replication. Despite influenza A and B viruses belonging to separate genera of the Orthomyxoviridae family, their NP proteins share a relatively high level of sequence conservation. However, NP of influenza B viruses (BNP) contains an evolutionarily conserved N-terminal 50-amino-acid extension that is absent from NP of influenza A viruses. There is conflicting evidence as to the functions of the BNP N-terminal extension; however, this has never been assessed in the context of viral infection. We have used reverse genetics to assess the significance of this region on the functions of BNP and virus viability. The truncation of more than three amino acids prevented virus recovery, suggesting that the N-terminal extension is essential for virus viability. Mutational analysis indicated that multiple regions of the protein are involved in the nuclear localization of BNP, with the entire N-terminal extension required for this to function efficiently. Viruses containing mutations in the first 10 residues of BNP demonstrated few differences in nuclear localization; however, the viruses exhibited significant reductions in viral mRNA transcription and genome replication, resulting in significantly attenuated phenotypes. Mutations introduced to ablate a previously reported nuclear localization signal also resulted in a significant decrease in mRNA production during early stages of viral replication. Overall, our results demonstrate that the N-terminal extension of BNP is essential to virus viability not only for directing nuclear localization of BNP but also for regulating viral mRNA transcription and genome replication. IMPORTANCE: The multifunctional NP of influenza viruses has roles throughout the viral replication cycle; therefore, it is essential for virus viability. Despite high levels of homology between the NP of influenza A and B viruses, the NP of influenza B virus contains an evolutionarily conserved 50 amino-acid N-terminal extension that is absent from the NP of influenza A viruses. In this study, we show that this N-terminal extension is essential for virus viability, and we confirm and expand upon recent findings that this region of BNP is required for nuclear localization of the protein. Furthermore, we demonstrate for the first time that the N terminus of BNP is involved in regulating viral mRNA transcription and replication of the viral genome. As the NP of influenza A virus lacks this N-terminal extension, these viruses may have evolved separate mechanisms to regulate these processes. PMID- 25122786 TI - The temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus PB2, PB1, and NP genes are influenced by the species of origin of the PB2 gene in reassortant viruses derived from influenza A/California/07/2009 and A/WSN/33 viruses. AB - Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (>= 100 fold) replication at 39 degrees C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391 E, 581 G, and 661 T), PB2 (265 S), and NP (34 G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04(ts sig) and CA07(ts sig) viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39 degrees C, but the replication of WSN(ts sig) was restricted >= 100-fold compared to that at 33 degrees C. Reassortant CA07(ts sig) viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication >= 100 fold at 39 degrees C. In ferrets, the CA07(ts sig) virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07(ts sig) virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses. IMPORTANCE: Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our data indicate this is associated with the presence of a PB2 gene segment derived from an avian influenza virus. We show that a reassortant 2009 pandemic H1N1 virus with the ts signature from a licensed LAIV donor virus is ts in vitro and attenuated in vivo when the PB2 gene is derived from a human origin virus but not from an avian virus. Our study provides information that could benefit the rational design of alternative LAIV backbones against animal origin influenza viruses. PMID- 25122788 TI - Epitope mapping of the hemagglutinin molecule of A/(H1N1)pdm09 influenza virus by using monoclonal antibody escape mutants. AB - We determined the antigenic structure of pandemic influenza A(H1N1)pdm09 virus hemagglutinin (HA) using 599 escape mutants that were selected using 16 anti-HA monoclonal antibodies (MAbs) against A/Narita/1/2009. The sequencing of mutant HA genes revealed 43 amino acid substitutions at 24 positions in three antigenic sites, Sa, Sb, and Ca2, which were previously mapped onto A/Puerto Rico/8/34 (A/PR/8/34) HA (A. J. Caton, G. G. Brownlee, J. W. Yewdell, and W. Gerhard, Cell 31:417-427, 1982), and an undesignated site, i.e., amino acid residues 141, 142, 143, 171, 172, 174, 177, and 180 in the Sa site, residues 170, 173, 202, 206, 210, 211, and 212 in the Sb site, residues 151, 154, 156, 157, 158, 159, 200, and 238 in the Ca2 site, and residue 147 in the undesignated site (numbering begins at the first methionine). Sixteen MAbs were classified into four groups based on their cross-reactivity with the panel of escape mutants in the hemagglutination inhibition test. Among them, six MAbs targeting the Sa and Sb sites recognized both residues at positions 172 and 173. MAb n2 lost reactivity when mutations were introduced at positions 147, 159 (site Ca2), 170 (site Sb), and 172 (site Sa). We designated the site consisting of these residues as site Pa. From 2009 to 2013, no antigenic drift was detected for the A(H1N1)pdm09 viruses. However, if a novel variant carrying a mutation at a position involved in the epitopes of several MAbs, such as 172, appeared, such a virus would have the advantage of becoming a drift strain. IMPORTANCE: The first influenza pandemic of the 21st century occurred in 2009 with the emergence of a novel virus originating with swine influenza, A(H1N1)pdm09. Although HA of A(H1N1)pdm09 has a common origin (1918 H1N1) with seasonal H1N1, the antigenic divergence of HA between the seasonal H1N1 and A(H1N1)pdm09 viruses gave rise to the influenza pandemic in 2009. To take precautions against the antigenic drift of the A(H1N1)pdm09 virus in the near future, it is important to identify its precise antigenic structure. To obtain various mutants that are not neutralized by MAbs, it is important to neutralize several plaque-cloned parent viruses rather than only a single parent virus. We characterized 599 escape mutants that were obtained by neutralizing four parent viruses of A(H1N1)pdm09 in the presence of 16 MAbs. Consequently, we were able to determine the details of the antigenic structure of HA, including a novel epitope. PMID- 25122789 TI - The matrix gene segment destabilizes the acid and thermal stability of the hemagglutinin of pandemic live attenuated influenza virus vaccines. AB - The threat of future influenza pandemics and their potential for rapid spread, morbidity, and mortality has led to the development of pandemic vaccines. We generated seven reassortant pandemic live attenuated influenza vaccines (pLAIVs) with the hemagglutinin (HA) and neuraminidase (NA) genes derived from animal influenza viruses on the backbone of the six internal protein gene segments of the temperature sensitive, cold-adapted (ca) A/Ann Arbor/60 (H2N2) virus (AA/60 ca) of the licensed seasonal LAIV. The pLAIV viruses were moderately to highly restricted in replication in seronegative adults; we sought to determine the biological basis for this restriction. Avian influenza viruses generally replicate at higher temperatures than human influenza viruses and, although they shared the same backbone, the pLAIV viruses had a lower shutoff temperature than seasonal LAIV viruses, suggesting that the HA and NA influence the degree of temperature sensitivity. The pH of HA activation of highly pathogenic avian influenza viruses was greater than human and low-pathogenicity avian influenza viruses, as reported by others. However, pLAIV viruses had a consistently higher pH of HA activation and reduced HA thermostability compared to the corresponding wild-type parental viruses. From studies with single-gene reassortant viruses bearing one gene segment from the AA/60 ca virus in recombinant H5N1 or pH1N1 viruses, we found that the lower HA thermal stability and increased pH of HA activation were associated with the AA/60 M gene. Together, the impaired HA acid and thermal stability and temperature sensitivity likely contributed to the restricted replication of the pLAIV viruses we observed in seronegative adults. IMPORTANCE: There is increasing evidence that the HA stability of influenza viruses depends on the virus strain and host species and that HA stability can influence replication, virulence, and transmission of influenza A viruses in different species. We investigated the HA stability of pandemic live attenuated influenza vaccine (pLAIV) viruses and observed that the pLAIV viruses consistently had a less stable HA than the corresponding wild-type influenza viruses. The reduced HA stability and temperature sensitivity of the pLAIV viruses may account for their restricted replication in clinical trials. PMID- 25122791 TI - Stearoyl coenzyme A desaturase 1 is associated with hepatitis C virus replication complex and regulates viral replication. AB - The hepatitis C virus (HCV) life cycle is tightly regulated by lipid metabolism of host cells. In order to identify host factors involved in HCV propagation, we have recently screened a small interfering RNA (siRNA) library targeting host genes that control lipid metabolism and lipid droplet formation using cell culture-grown HCV (HCVcc)-infected cells. We selected and characterized the gene encoding stearoyl coenzyme A (CoA) desaturase 1 (SCD1). siRNA-mediated knockdown or pharmacological inhibition of SCD1 abrogated HCV replication in both subgenomic replicon and Jc1-infected cells, while exogenous supplementation of either oleate or palmitoleate, products of SCD1 activity, resurrected HCV replication in SCD1 knockdown cells. SCD1 was coimmunoprecipitated with HCV nonstructural proteins and colocalized with both double-stranded RNA (dsRNA) and HCV nonstructural proteins, indicating that SCD1 is associated with HCV replication complex. Moreover, SCD1 was fractionated and enriched with HCV nonstructural proteins at detergent-resistant membrane. Electron microscopy data showed that SCD1 is required for NS4B-mediated intracellular membrane rearrangement. These data further support the idea that SCD1 is associated with HCV replication complex and that its products may contribute to the proper formation and maintenance of membranous web structures in HCV replication complex. Collectively, these data suggest that manipulation of SCD1 activity may represent a novel host-targeted antiviral strategy for the treatment of HCV infection. IMPORTANCE: Stearoyl coenzyme A (CoA) desaturase 1 (SCD1), a liver specific enzyme, regulates hepatitis C virus (HCV) replication through its enzyme activity. HCV nonstructural proteins are associated with SCD1 at detergent resistant membranes, and SCD1 is enriched on the lipid raft by HCV infection. Therein, SCD1 supports NS4B-mediated membrane rearrangement to provide a suitable microenvironment for HCV replication. We demonstrated that either genetic or chemical knockdown of SCD1 abrogated HCV replication in both replicon cells and HCV-infected cells. These findings provide novel mechanistic insights into the roles of SCD1 in HCV replication. PMID- 25122790 TI - Methyltransferase-defective avian metapneumovirus vaccines provide complete protection against challenge with the homologous Colorado strain and the heterologous Minnesota strain. AB - Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. Since its discovery in the 1970s, aMPV has been recognized as an economically important pathogen in the poultry industry worldwide. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at guanine N-7 (G-N-7) and ribose 2'-O positions. In this study, we generated a panel of recombinant aMPV (raMPV) Colorado strains carrying mutations in the S-adenosyl methionine (SAM) binding site in the CR VI of L protein. These recombinant viruses were specifically defective in ribose 2'-O, but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of specific-pathogen-free (SPF) young turkeys. Importantly, turkeys vaccinated with these MTase-defective raMPVs triggered a high level of neutralizing antibody and were completely protected from challenge with homologous aMPV Colorado strain and heterologous aMPV Minnesota strain. Collectively, our results indicate (i) that aMPV lacking 2'-O methylation is highly attenuated in vitro and in vivo and (ii) that inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for aMPV and perhaps other paramyxoviruses. IMPORTANCE: Paramyxoviruses include many economically and agriculturally important viruses such as avian metapneumovirus (aMPV), and Newcastle disease virus (NDV), human pathogens such as human respiratory syncytial virus, human metapneumovirus, human parainfluenza virus type 3, and measles virus, and highly lethal emerging pathogens such as Nipah virus and Hendra virus. For many of them, there is no effective vaccine or antiviral drug. These viruses share common strategies for viral gene expression and replication. During transcription, paramyxoviruses produce capped, methylated, and polyadenylated mRNAs. Using aMPV as a model, we found that viral ribose 2'-O methyltransferase (MTase) is a novel approach to rationally attenuate the virus for vaccine purpose. Recombinant aMPV (raMPV) lacking 2'-O MTase were not only highly attenuated in turkeys but also provided complete protection against the challenge of homologous and heterologous aMPV strains. This novel approach can be applicable to other animal and human paramyxoviruses for rationally designing live attenuated vaccines. PMID- 25122792 TI - Kinetic and phenotypic analysis of CD8+ T cell responses after priming with alphavirus replicons and homologous or heterologous booster immunizations. AB - Alphavirus replicons are potent inducers of CD8(+) T cell responses and thus constitute an attractive vaccine vector platform for developing novel vaccines. However, the kinetics and memory phenotype of CD8(+) T cell responses induced by alphavirus replicons are not well characterized. Furthermore, little is known how priming with alphavirus replicons affects booster immune responses induced by other vaccine modalities. We demonstrate here that a single immunization with an alphavirus replicon, administered as viral particles or naked DNA, induced an antigen-specific CD8(+) T cell response that had a sharp peak, followed by a rapid contraction. Administering a homologous boost before contraction had occurred did not further increase the response. In contrast, boosting after contraction when CD8(+) T cells had obtained a memory phenotype (based on CD127/CD62L expression), resulted in maintenance of CD8(+) T cells with a high recall capacity (based on CD27/CD43 expression). Increasing the dose of replicon particles promoted T effector memory (Tem) and inhibited T central memory development. Moreover, infection with a replicating alphavirus induced a similar distribution of CD8(+) T cells as the replicon vector. Lastly, the distribution of T cell subpopulations induced by a DNA-launched alphavirus replicon could be altered by heterologous boosts. For instance, boosting with a poxvirus vector (MVA) favored expansion of the Tem compartment. In summary, we have characterized the antigen-specific CD8(+) T cell response induced by alphavirus replicon vectors and demonstrated how it can be altered by homologous and heterologous boost immunizations. IMPORTANCE: Alphavirus replicons are promising vaccine candidates against a number of diseases and are by themselves developed as vaccines against, for example, Chikungunya virus infection. Replicons are also considered to be used for priming, followed by booster immunization using different vaccine modalities. In order to rationally design prime-boost immunization schedules with these vectors, characterization of the magnitude and phenotype of CD8(+) T cell responses induced by alphavirus replicons is needed. Here, we demonstrate how factors such as timing and dose affect the phenotypes of memory T cell populations induced by immunization with alphavirus replicons. These findings are important for designing future clinical trials with alphaviruses, since they can be used to tailor vaccination regimens in order to induce a CD8(+) T cell response that is optimal for control and/or clearance of a specific pathogen. PMID- 25122794 TI - The VP4 peptide of hepatitis A virus ruptures membranes through formation of discrete pores. AB - Membrane-active peptides, components of capsid structural proteins, assist viruses in overcoming the host membrane barrier in the initial stages of infection. Several such peptides have been identified, and their roles in membrane fusion or disruption have been characterized through biophysical studies. In several members of the Picornaviridae family, the role of the VP4 structural peptide in cellular-membrane penetration is well established. However, there is not much information on the membrane-penetrating capsid components of hepatitis A virus (HAV), an unusual member of this family. The VP4 peptide of HAV differs from its analogues in other picornaviruses in being significantly shorter in length and in lacking a signal for myristoylation, thought to be a critical requisite for VP4-mediated membrane penetration. Here we report, for the first time, that the atypical VP4 in HAV contains significant membrane-penetrating activity. Using a combination of biophysical assays and molecular dynamics simulation studies, we show that VP4 integrates into membrane vesicles through its N-terminal region to finally form discrete pores of 5- to 9-nm diameter, which induces leakage in the vesicles without altering their overall size or shape. We further demonstrate that the membrane activity of VP4 is specific toward vesicles mimicking the lipid content of late endosomes at acidic pH. Taken together, our data indicate that VP4 might be essential for the penetration of host endosomal membranes and release of the viral genome during HAV entry. IMPORTANCE: Hepatitis A virus causes acute hepatitis in humans through the fecal oral route and is particularly prevalent in underdeveloped regions with poor hygienic conditions. Although a vaccine for HAV exists, its high cost makes it unsuitable for universal application in developing countries. Studies on host virus interaction for HAV have been hampered due to a lack of starting material, since the virus is extremely slow growing in culture. Among the unknown aspects of the HAV life cycle is its manner of host membrane penetration, which is one of the most important initial steps in viral infection. Here, we present data to suggest that a small peptide, VP4, a component of the HAV structural polyprotein, might be essential in helping the viral genome cross cell membranes during entry. It is hoped that this work might help in elucidating the manner of initial host cell interaction by HAV. PMID- 25122793 TI - Apolipoprotein E likely contributes to a maturation step of infectious hepatitis C virus particles and interacts with viral envelope glycoproteins. AB - The assembly of infectious hepatitis C virus (HCV) particles is tightly linked to components of the very-low-density lipoprotein (VLDL) pathway. We and others have shown that apolipoprotein E (ApoE) plays a major role in production of infectious HCV particles. However, the mechanism by which ApoE contributes to virion assembly/release and how it gets associated with the HCV particle is poorly understood. We found that knockdown of ApoE reduces titers of infectious intra- and extracellular HCV but not of the related dengue virus. ApoE depletion also reduced amounts of extracellular HCV core protein without affecting intracellular core amounts. Moreover, we found that ApoE depletion affected neither formation of nucleocapsids nor their envelopment, suggesting that ApoE acts at a late step of assembly, such as particle maturation and infectivity. Importantly, we demonstrate that ApoE interacts with the HCV envelope glycoproteins, most notably E2. This interaction did not require any other viral proteins and depended on the transmembrane domain of E2 that also was required for recruitment of HCV envelope glycoproteins to detergent-resistant membrane fractions. These results suggest that ApoE plays an important role in HCV particle maturation, presumably by direct interaction with viral envelope glycoproteins. IMPORTANCE: The HCV replication cycle is tightly linked to host cell lipid pathways and components. This is best illustrated by the dependency of HCV assembly on lipid droplets and the VLDL component ApoE. Although the role of ApoE for production of infectious HCV particles is well established, it is still poorly understood how ApoE contributes to virion formation and how it gets associated with HCV particles. Here, we provide experimental evidence that ApoE likely is required for an intracellular maturation step of HCV particles. Moreover, we demonstrate that ApoE associates with the viral envelope glycoproteins. This interaction appears to be dispensable for envelopment of virus particles but likely contributes to the quality control of secreted infectious virions. These results shed new light on the exploitation of host cell lipid pathways by HCV and the link of viral particle assembly to the VLDL component ApoE. PMID- 25122795 TI - Inhibition of breast cancer cell proliferation through disturbance of the calcineurin/NFAT pathway by human herpesvirus 6B U54 tegument protein. AB - Nuclear factor of activated T cell (NFAT) proteins are key regulators involved in multiple physiological mechanisms, such as immune response and cell growth. The capacity of selective calcineurin/NFAT inhibitors to decrease NFAT-dependent cancer cell progression, particularly in breast cancer, has already been demonstrated. In this study, we report a role for the human herpesvirus 6B (HHV 6B) U54 tegument protein in inhibiting MCF-7 breast cancer cell proliferation by inhibiting NFAT activation. PMID- 25122796 TI - High frequencies of polyfunctional CD8+ NK cells in chronic HIV-1 infection are associated with slower disease progression. AB - Natural killer (NK) cells are effector and regulatory innate immune cells and play a critical role in the first line of defense against various viral infections. Although previous reports have indicated the vital contributions of NK cells to HIV-1 immune control, nongenetic NK cell parameters directly associated with slower disease progression have not been defined yet. In a longitudinal, retrospective study of 117 untreated HIV-infected subjects, we show that higher frequencies as well as the absolute numbers of CD8(+) CD3(-) lymphocytes are linked to delayed HIV-1 disease progression. We show that the majority of these cells are well-described blood NK cells. In a subsequent cross sectional study, we demonstrate a significant loss of CD8(+) NK cells in untreated HIV-infected individuals, which correlated with HIV loads and inversely correlated with CD4(+) T cell counts. CD8(+) NK cells had modestly higher frequencies of CD57-expressing cells than CD8(-) cells, but CD8(+) and CD8(-) NK cells showed no differences in the expression of a number of activating and inhibiting NK cell receptors. However, CD8(+) NK cells exhibited a more functional profile, as detected by cytokine production and degranulation. IMPORTANCE: We demonstrate that the frequency of highly functional CD8(+) NK cells is inversely associated with HIV-related disease markers and linked with delayed disease progression. These results thus indicate that CD8(+) NK cells represent a novel NK cell-derived, innate immune correlate with an improved clinical outcome in HIV infection. PMID- 25122797 TI - Inhibition of interleukin-2 gene expression by human herpesvirus 6B U54 tegument protein. AB - Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen causing lifelong infections in approximately 95% of humans worldwide. To persist within its host, HHV-6B has developed several immune evasion mechanisms, such as latency, during which minimal proteins are expressed, and the ability to disturb innate and adaptive immune responses. The primary cellular targets of HHV-6B are CD4(+) T cells. Previous studies by Flamand et al. (L. Flamand, J. Gosselin, I. Stefanescu, D. Ablashi, and J. Menezes, Blood 85:1263-1271, 1995) reported on the capacity of HHV-6A as well as UV-irradiated HHV-6A to inhibit interleukin-2 (IL 2) synthesis in CD4(+) lymphocytes, suggesting that viral structural components could be responsible for this effect. In the present study, we identified the HHV 6B U54 tegument protein (U54) as being capable of inhibiting IL-2 expression. U54 binds the calcineurin (CaN) phosphatase enzyme, causing improper dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T cells) proteins, resulting in suboptimal IL-2 gene transcription. The U54 GISIT motif (amino acids 293 to 297), analogous to the NFAT PXIXIT motif, contributed to the inhibition of NFAT activation. IMPORTANCE Human herpesvirus 6A (HHV-6A) and HHV-6B are associated with an increasing number of pathologies. These viruses have developed strategies to avoid the immune response allowing them to persist in the host. Several studies have illustrated mechanisms by which HHV-6A and HHV 6B are able to disrupt host defenses (reviewed in L. Dagna, J. C. Pritchett, and P. Lusso, Future Virol. 8:273-287, 2013, doi:10.2217/fvl.13.7). Previous work informed us that HHV-6A is able to suppress synthesis of interleukin-2 (IL-2), a key immune growth factor essential for adequate T lymphocyte proliferation and expansion. We obtained evidence that HHV-6B also inhibits IL-2 gene expression and identified the mechanisms by which it does so. Our work led us to the identification of U54, a virion-associated tegument protein, as being responsible for suppression of IL-2. Consequently, we have identified HHV-6B U54 protein as playing a role in immune evasion. These results further contribute to our understanding of HHV-6 interactions with its human host and the efforts deployed to ensure its long-term persistence. PMID- 25122798 TI - Polyomavirus small T antigen interacts with yes-associated protein to regulate cell survival and differentiation. AB - Murine polyomavirus small t antigen (PyST) regulates cell cycle, cell survival, apoptosis, and differentiation and cooperates with middle T antigen (MT) to transform primary cells in vitro and in vivo. Like all polyomavirus T antigens, PyST functions largely via its interactions with host cell proteins. Here, we show that PyST binds both Yes-associated protein 1 (YAP1) and YAP2, integral parts of the Hippo signaling pathway, which is a subject of increasing interest in human cancer. The transcription factor TEAD, which is a known target of YAP, is also found in PyST complexes. PyST enhanced YAP association with protein phosphatase 2A (PP2A), leading to decreased YAP phosphorylation. PyST increased YAP levels by decreasing its degradation. This effect was mediated by a reduction in YAP association with beta-transducin repeat protein (betaTRCP), which is known to regulate YAP turnover in a phosphorylation-dependent manner. Genetic analysis has identified PyST mutants defective in YAP binding. These mutants demonstrated that YAP binding is important for PyST to block myoblast differentiation and to synergize with the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) to promote cell death in 3T3-L1 preadipocytes placed under differentiation conditions. In addition to YAP binding, both of these phenotypes require PyST binding to PP2A. Importance: The Hippo/YAP pathway is a highly conserved cascade important for tissue development and homeostasis. Defects in this pathway are increasingly being associated with cancer. Polyomavirus small t antigen is a viral oncogene that cooperates with middle T antigen in transformation. On its own, small t antigen controls cell survival and differentiation. By binding YAP, small t antigen brings it together with protein phosphatase 2A. This work shows how this association of small t antigen with YAP is important for its effects on cell phenotype. It also suggests that PyST can be used to characterize cellular processes that are regulated by YAP. PMID- 25122799 TI - The composition of West Nile virus lipid envelope unveils a role of sphingolipid metabolism in flavivirus biogenesis. AB - West Nile virus (WNV) is an emerging zoonotic mosquito-borne flavivirus responsible for outbreaks of febrile illness and meningoencephalitis. The replication of WNV takes place on virus-modified membranes from the endoplasmic reticulum of the host cell, and virions acquire their envelope by budding into this organelle. Consistent with this view, the cellular biology of this pathogen is intimately linked to modifications of the intracellular membranes, and the requirement for specific lipids, such as cholesterol and fatty acids, has been documented. In this study, we evaluated the impact of WNV infection on two important components of cellular membranes, glycerophospholipids and sphingolipids, by mass spectrometry of infected cells. A significant increase in the content of several glycerophospholipids (phosphatidylcholine, plasmalogens, and lysophospholipids) and sphingolipids (ceramide, dihydroceramide, and sphingomyelin) was noticed in WNV-infected cells, suggesting that these lipids have functional roles during WNV infection. Furthermore, the analysis of the lipid envelope of WNV virions and recombinant virus-like particles revealed that their envelopes had a unique composition. The envelopes were enriched in sphingolipids (sphingomyelin) and showed reduced levels of phosphatidylcholine, similar to sphingolipid-enriched lipid microdomains. Inhibition of neutral sphingomyelinase (which catalyzes the hydrolysis of sphingomyelin into ceramide) by either pharmacological approaches or small interfering RNA-mediated silencing reduced the release of flavivirus virions as well as virus-like particles, suggesting a role of sphingomyelin-to-ceramide conversion in flavivirus budding and confirming the importance of sphingolipids in the biogenesis of WNV. Importance: West Nile virus (WNV) is a neurotropic flavivirus spread by mosquitoes that can infect multiple vertebrate hosts, including humans. There is no specific vaccine or therapy against this pathogen licensed for human use. Since the multiplication of this virus is associated with rearrangements of host cell membranes, we analyzed the effect of WNV infection on different cellular lipids that constitute important membrane components. The levels of multiple lipid species were increased in infected cells, pointing to the induction of major alterations of cellular lipid metabolism by WNV infection. Interestingly, certain sphingolipids, which were increased in infected cells, were also enriched in the lipid envelope of the virus, thus suggesting a potential role during virus assembly. We further verified the role of sphingolipids in the production of WNV by means of functional analyses. This study provides new insight into the formation of flavivirus infectious particles and the involvement of sphingolipids in the WNV life cycle. PMID- 25122800 TI - Regulation of autophagic activation by Rta of Epstein-Barr virus via the extracellular signal-regulated kinase pathway. AB - Autophagy is an intracellular degradation pathway that provides a host defense mechanism against intracellular pathogens. However, many viruses exploit this mechanism to promote their replication. This study shows that lytic induction of Epstein-Barr virus (EBV) increases the membrane-bound form of LC3 (LC3-II) and LC3-containing punctate structures in EBV-positive cells. Transfecting 293T cells with a plasmid that expresses Rta also induces autophagy, revealing that Rta is responsible for autophagic activation. The activation involves Atg5, a key component of autophagy, but not the mTOR pathway. The expression of Rta also activates the transcription of the genes that participate in the formation of autophagosomes, including LC3A, LC3B, and ATG9B genes, as well as those that are involved in the regulation of autophagy, including the genes TNF, IRGM, and TRAIL. Additionally, treatment with U0126 inhibits the Rta-induced autophagy and the expression of autophagy genes, indicating that the autophagic activation is caused by the activation of extracellular signal-regulated kinase (ERK) signaling by Rta. Finally, the inhibition of autophagic activity by an autophagy inhibitor, 3-methyladenine, or Atg5 small interfering RNA, reduces the expression of EBV lytic proteins and the production of viral particles, revealing that autophagy is critical to EBV lytic progression. This investigation reveals how an EBV-encoded transcription factor promotes autophagy to affect viral lytic development. PMID- 25122801 TI - Combined alphavirus replicon particle vaccine induces durable and cross protective immune responses against equine encephalitis viruses. AB - Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in macaques and demonstrated good protection against aerosol challenge with an epizootic VEEV-IAB virus, Trinidad donkey. Similarly, the EEEV replicon and V/W/E combination vaccine elicited neutralizing antibodies against EEEV and protected against aerosol exposure to a North American variety of EEEV. Both the WEEV replicon and combination V/W/E vaccination, however, elicited poor neutralizing antibodies to WEEV in macaques, and the protection conferred was not as strong. These results demonstrate that a combination V/W/E vaccine is possible for protection against aerosol challenge and that cross-interference between the vaccines is minimal. Importance: Three related viruses belonging to the genus Alphavirus cause severe encephalitis in humans: Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), and eastern equine encephalitis virus (EEEV). Normally transmitted by mosquitoes, these viruses can cause disease when inhaled, so there is concern that these viruses could be used as biological weapons. Prior reports have suggested that vaccines for these three viruses might interfere with one another. We have developed a combined vaccine for Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis expressing the surface proteins of all three viruses. In this report we demonstrate in both mice and macaques that this combined vaccine is safe, generates a strong immune response, and protects against aerosol challenge with the viruses that cause Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis. PMID- 25122804 TI - My second-favourite medical journal. PMID- 25122802 TI - DESC1 and MSPL activate influenza A viruses and emerging coronaviruses for host cell entry. AB - The type II transmembrane serine protease (TTSP) TMPRSS2 cleaves and activates the influenza virus and coronavirus surface proteins. Expression of TMPRSS2 is essential for the spread and pathogenesis of H1N1 influenza viruses in mice. In contrast, H3N2 viruses are less dependent on TMPRSS2 for viral amplification, suggesting that these viruses might employ other TTSPs for their activation. Here, we analyzed TTSPs, reported to be expressed in the respiratory system, for the ability to activate influenza viruses and coronaviruses. We found that MSPL and, to a lesser degree, DESC1 are expressed in human lung tissue and cleave and activate the spike proteins of the Middle East respiratory syndrome and severe acute respiratory syndrome coronaviruses for cell-cell and virus-cell fusion. In addition, we show that these proteases support the spread of all influenza virus subtypes previously pandemic in humans. In sum, we identified two host cell proteases that could promote the amplification of influenza viruses and emerging coronaviruses in humans and might constitute targets for antiviral intervention. Importance: Activation of influenza viruses by host cell proteases is essential for viral infectivity and the enzymes responsible are potential targets for antiviral intervention. The present study demonstrates that two cellular serine proteases, DESC1 and MSPL, activate influenza viruses and emerging coronaviruses in cell culture and, because of their expression in human lung tissue, might promote viral spread in the infected host. Antiviral strategies aiming to prevent viral activation might thus need to encompass inhibitors targeting MSPL and DESC1. PMID- 25122806 TI - Industry involvement in continuing medical education: time to say no. PMID- 25122807 TI - Realigning training with need: A case for mandatory family medicine resident experience in community-based care of the frail elderly. PMID- 25122810 TI - Logic of care. PMID- 25122803 TI - Counteracting effects of cellular Notch and Epstein-Barr virus EBNA2: implications for stromal effects on virus-host interactions. AB - A number of diverse environmental cues have been linked to B lymphocyte differentiation and activation. One such cue, Notch-2, may be particularly relevant to the biology of infection with Epstein-Barr virus (EBV), which colonizes the B cell compartment. Activated Notch and EBV nuclear antigen 2 (EBNA2) both function as transcriptional activators by virtue of their interactions with the transcription factor RBP-Jkappa. Although EBNA2 and activated Notch appear to have partially overlapping functions, we now report that activated Notch counteracts a crucial EBNA2 function both in newly infected primary B cells and in lymphoblastoid cell lines (LCLs). EBNA2 is directly responsible for the initiation of transcription of the majority of EBV proteins associated with type III latency, leading to the outgrowth of LCLs. One of the key proteins driving this outgrowth is latent membrane protein 1 (LMP1), which is regulated by an EBNA2-responsive element within its ED-L1 promoter. Activation of Notch-2 via Delta-like ligand 1 inhibits EBNA2-mediated initiation of LMP1 transcription. Furthermore, ligated Notch-2 also efficiently turns off LMP1 expression from the ED-L1 promoter in LCLs already expressing LMP1. Modulation of EBV gene expression by Notch was not confined to EBNA2-dependent events. Activated Notch-2 also inhibited EBV entry into the lytic cycle in a B cell non Hodgkin's lymphoma line by upregulating the cellular transcription factor Zeb2, which represses the transcription of BZLF1. These results support the concept that in vivo, cumulative signals from the microenvironment downregulate EBV gene expression in B cells to the latency 0 gene expression profile observed in B cells entering the peripheral blood. Importance: Experimental infection of resting B cells by Epstein-Barr virus leads to the growth transformation program of virus gene expression and the outgrowth of lymphoblastoid cell lines. Previous studies at the single-cell level revealed complex cellular and viral signaling networks regulating transcription of the viral genome. This study demonstrates that viral gene expression can also be radically altered by molecules expressed on stromal cells in the microenvironment of lymphoid tissue, specifically, Delta like ligand 1 on stromal cells ligating Notch-2 on infected B cells. Activation of Notch interferes with the transactivation function of EBNA2, downregulates the expression of LMP1 and LMP2a, and inhibits the activation of lytic virus replication in a B cell non-Hodgkin's lymphoma line by preventing expression of BZLF1. The significance of these observations is that they indicate new mechanisms whereby the microenvironment in normal lymphoid tissue may facilitate the repression of viral gene expression, enabling establishment of true latency in memory B cells. PMID- 25122811 TI - Clinical review or hypothesis? PMID- 25122812 TI - Response. PMID- 25122814 TI - Guideline for referral of patients with suspected lung cancer by family physicians and other primary care providers. AB - OBJECTIVE: The aim of this guideline is to assist FPs and other primary care providers with recognizing features that should raise their suspicions about the presence of lung cancer in their patients. COMPOSITION OF THE COMMITTEE: Committee members were selected from among the regional primary care leads from the Cancer Care Ontario Provincial Primary Care and Cancer Network and from among the members of the Cancer Care Ontario Lung Cancer Disease Site Group. METHODS: This guideline was developed through systematic review of the evidence base, synthesis of the evidence, and formal external review involving Canadian stakeholders to validate the relevance of recommendations. REPORT: Evidence-based guidelines were developed to improve the management of patients presenting with clinical features of lung cancer within the Canadian context. CONCLUSION: Earlier identification and referral of patients with lung cancer might ultimately help improve lung cancer morbidity and mortality. These guidelines might also be of value for informing the development of lung cancer diagnostic programs and for helping policy makers to ensure appropriate resources are in place. PMID- 25122815 TI - Guideline for referral of patients with suspected colorectal cancer by family physicians and other primary care providers. AB - OBJECTIVE: The aim of this guideline is to assist FPs and other primary care providers with recognizing features that should raise their suspicions about the presence of colorectal cancer (CRC) in their patients. COMPOSITION OF THE COMMITTEE: Committee members were selected from among the regional primary care leads from the Cancer Care Ontario Provincial Primary Care and Cancer Network, the members of the Ontario Colorectal Cancer Screening Advisory Committee, and the members of the Cancer Care Ontario Gastrointestinal Cancer Disease Site Group. METHODS: This guideline was developed through systematic review of the evidence base, synthesis of the evidence, and formal external review involving Canadian stakeholders to validate the relevance of recommendations. REPORT: Evidence-based guidelines were developed to improve the management of patients presenting with clinical features of CRC within the Canadian context. CONCLUSION: The judicious balancing of suspicion of CRC and level of risk of CRC should encourage timely referral by FPs and primary care providers. This guideline might also inform indications for referral to CRC diagnostic assessment programs. PMID- 25122818 TI - Practical strategies for prevention and treatment of heat-induced illness. PMID- 25122816 TI - Consuming non-alcoholic beer and other beverages during pregnancy and breastfeeding. AB - QUESTION: An increasing number of my patients are asking about the safety of consuming non-alcoholic beer and other alcohol-free versions of alcoholic beverages during pregnancy and breastfeeding, as they believe that these drinks might be a "safer" alternative to regular alcoholic beverages. What are Motherisk's recommendations regarding these products? ANSWER: Such drinks might contain higher ethanol levels than what is indicated on their labels. As there is no known safe level of alcohol intake in pregnancy, abstinence from non-alcoholic beverages would eliminate any risk of fetal alcohol spectrum disorder. Although it is likely that moderate intake of non-alcoholic beverages would pose no harm to breastfed infants, briefly delaying breastfeeding after consumption of such drinks would ensure that the infant is not exposed to alcohol. PMID- 25122817 TI - Accidental digital epinephrine injection: to treat or not to treat? PMID- 25122820 TI - A horse-and-buggy kind of doctor. PMID- 25122821 TI - Dr Agnes Kluz MD CCFP. PMID- 25122822 TI - Balancing life and work. PMID- 25122819 TI - Colorectal cancer risk information presented by a nonphysician assistant does not increase screening rates. AB - OBJECTIVE: To determine the effectiveness of presenting individualized colorectal cancer (CRC) risk information for increasing CRC screening rates in primary care patients at above-average risk of CRC. DESIGN: Randomized controlled trial. SETTING: Georgia Regents University in Augusta-an academic family medicine clinic in the southeastern United States. PARTICIPANTS: Outpatients (50 to 70 years of age) scheduled for routine visits in the family medicine clinic who were determined to be at above-average risk of CRC. INTERVENTIONS: Individualized CRC risk information calculated from the Your Disease Risk tool compared with a standard CRC screening handout. MAIN OUTCOME MEASURES: Intention to complete CRC screening. Secondary measures included the proportions of subjects completing fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. RESULTS: A total of 1147 consecutive records were reviewed to determine eligibility. Overall, 210 (37.7%) of 557 eligible participants were randomized to receive either individualized CRC risk information (prepared by a research assistant) or a standard CRC screening handout. The intervention group had a mean (SD) age of 55.7 (4.8) years and the control group had a mean (SD) age of 55.6 (4.6) years. Two-thirds of the participants in each group were female. The intervention group and the control group were matched by race (P = .40). There was no significant difference between groups for intention to complete CRC screening (P = .58). Overall, 26.7% of the intervention participants and 27.7% of the control participants completed 1 or more CRC screening tests (P = .66). CONCLUSION: Presentation of individualized CRC risk information by a nonphysician assistant as a decision aid did not result in higher CRC screening rates in primary care patients compared with presentation of general CRC screening information. Future research is needed to determine if physician presentation of CRC risk information would result in increased screening rates compared with research assistant presentation. PMID- 25122825 TI - Meet Dr Pamela Eisener-Parsche: Our new Associate Executive Director and Director of Academic Family Medicine. PMID- 25122828 TI - Statins and cognitive impairment. PMID- 25122830 TI - Systematic review of guidelines for the management of suspected lung cancer in primary care. AB - OBJECTIVE: To systematically review the literature and provide an update and integration of existing peer-reviewed guidelines with recent systematic reviews and with primary studies related to the early recognition and management of lung cancer in primary care. DATA SOURCES: MEDLINE and EMBASE were searched for relevant articles. The quality of the evidence to support existing guideline recommendations, and the consistency of recommendations with updated evidence, were assessed. Applicability in a Canadian primary care setting was also evaluated. STUDY SELECTION: All studies that explored signs or symptoms of or risk factors for lung cancer in the primary care setting were included. All diagnostic studies in which symptomatic primary care patients underwent 1 or more investigations were also searched. SYNTHESIS: Recommendations were consistent among guidelines despite a paucity of supporting evidence. Updated evidence provided further support for the recommendations. Recommendations for identifying signs and symptoms of lung cancer presenting in primary care and for initial management can be adopted and applied within a Canadian primary care setting. CONCLUSION: This updated review of recommendations might help promote evidence based practice and, ultimately, more timely management and improved prognosis for lung cancer patients. It might also assist in the development of lung cancer diagnostic assessment programs. PMID- 25122831 TI - Systematic review of clinical features of suspected colorectal cancer in primary care. AB - OBJECTIVE: To systematically review the diagnostic accuracy of clinical features associated with colorectal cancer (CRC) presenting in primary care. DATA SOURCES: MEDLINE and EMBASE were searched for studies in primary care that provided information on clinical features predictive of CRC. Positive predictive values were used to guide the determination of clinical features associated with increased risk of CRC. STUDY SELECTION: Systematic reviews or primary studies that provided possible clinical features predictive of CRC were included. SYNTHESIS: Clinical features of patients presenting in primary care that are associated with increased risk of CRC, listed in descending order of association, included palpable rectal or abdominal mass; rectal bleeding combined with weight loss; iron deficiency anemia; rectal bleeding mixed with stool; rectal bleeding in the absence of perianal symptoms; rectal bleeding combined with change in bowel habits; dark rectal bleeding; rectal bleeding and diarrhea; and change in bowel habits. Being male and increasing age were also, in general, associated with increased risk of CRC. CONCLUSION: Recognition of clinical features associated with increased risk of CRC by FPs might help with earlier identification and referral among patients presenting in primary care. This review might help inform providers and CRC diagnostic assessment programs about indications for assessment and further investigation. PMID- 25122832 TI - Collaboration between family physicians and nurse clinicians: opinions of graduates in family medicine. AB - OBJECTIVE: To determine whether graduating family physicians are exposed to collaboration between family physicians and nurse clinicians during their training, as well as their opinions about shared care between doctors and nurse clinicians in the delivery of patient care. DESIGN: Anonymous online survey. SETTING: Two French-Canadian university family medicine residency programs. PARTICIPANTS: The 2010 and 2011 graduating family physicians (N = 343) from the University of Montreal and Laval University in Quebec. MAIN OUTCOME MEASURES: The extent to which nurse clinicians in graduating family physicians' training milieu were involved in preventive and curative patient care activities, and graduates' opinions about nurse clinicians sharing care with physicians. RESULTS: Of 343 graduates, 186 (54.2%) participated in the survey. Although as residents in family medicine their exposure to shared care with nurse clinicians was somewhat limited, respondents indicated that they were generally quite open to the idea of sharing care with nurse clinicians. More than 70% of respondents agreed or strongly agreed that nurse clinicians could adjust, according to protocols of clinical guidelines, the treatment of patients with diabetes, hypertension, and asthma, as well as regulate medication for pain control in terminally ill patients. By contrast, respondents were less favourable to nurse clinicians adjusting the treatment of patients with depression. More than 80% of respondents agreed or strongly agreed that nurse clinicians could initiate treatment via a medical directive for routine hormonal contraception, acne, uncomplicated cystitis, and sexually transmitted infections. Respondents' opinions on nurse clinicians initiating treatment for pharyngitis and otitis were more divided. CONCLUSION: Graduating family physicians are quite open to collaborating with nurse clinicians. Although they have observed some collaboration between physicians and nurses, there are areas of shared clinical activities in which they would benefit from further exposure and training. PMID- 25122833 TI - Simultaneous quantification of furanocoumarins from Aegle marmelos fruit pulp extract. AB - Aegle marmelos Correa (Rutaceae) is a prominent species in the Sub-Himalayan region, also found in central and south India, and has been widely used as remedy for diarrhea and dysentery. Unripe fruits show antiviral activity and prove to be a potent hypoglycemic agent. In this study, a high-performance liquid chromatography (HPLC) method for the simultaneous quantification of major furocoumarin components marmelosin, psoralen and bergapten in the extract from fruit pulp of A. marmelos has been developed. Components were found in the range of 5-6.5, >0.4-0.75 and >0.25 mg/g of dried fruit weight, respectively. The method was validated for linearity, precision, accuracy, robustness, limit of detection and limit of quantification. Linearity was determined over the range of 5-40 ug/mL (r > 0.965). Intra- and interday precision showed a relative standard deviation of <2.5%. The accuracy of the method was determined by a spike recovery study, and the average recoveries were 99.46, 101.04 and 100.8% for marmelosin, psoralen and bergapten, respectively. The proposed HPLC method was found to be simple, precise and specific and can be used simultaneously for the routine quality control of raw materials of A. marmelos fruit extracts and their products, and also other products containing these markers. PMID- 25122834 TI - Simultaneously optimizing spatial spectral features based on mutual information for EEG classification. AB - High performance of the brain-computer interface (BCI) needs efficient algorithms to extract discriminative features from raw electroencephalography (EEG) signals. In this paper, we present a novel scheme to extract spatial spectral features for the motor imagery-based BCI. The learning task is formulated by maximizing the mutual information between spatial spectral features (MMISS) and class labels, by which a unique objective function directly related to Bayes classification error is optimized. The spatial spectral features are assumed to follow a parametric Gaussian distribution, which has been validated by the normal distribution Mardia's test, and under this assumption the estimation of mutual information is derived. We propose a gradient based alternative and iterative learning algorithm to optimize the cost function and derive the spatial and spectral filters simultaneously. The experimental results on dataset IVa of BCI competition III and dataset IIa of BCI competition IV show that the proposed MMISS is able to efficiently extract discriminative features from motor imagery-based EEG signals to enhance the classification accuracy compared to other existing algorithms. PMID- 25122835 TI - Hierarchical String Cuts: A Translation, Rotation, Scale and Mirror Invariant Descriptor for Fast Shape Retrieval. AB - This paper presents a novel approach for both fast and accurately retrieving similar shapes. A hierarchical string cuts (HSC) method is proposed to partition a shape into multiple level curve segments of different lengths from a point moving around the contour to describe the shape gradually and completely from the global information to the finest details. At each hierarchical level, the curve segments are cut by strings to extract features that characterize the geometric and distribution properties in that particular level of details. The translation, rotation, scale and mirror invariant HSC descriptor enables a fast metric based matching to achieve the desired high accuracy. Encouraging experimental results on four databases demonstrated that the proposed method can consistently achieve higher (or similar) retrieval accuracies than the state-of-the-art benchmarks with a more than 120 times faster speed. This may suggest a new way of developing shape retrieval techniques in which a high accuracy can be achieved by a fast metric matching algorithm without using the time-consuming correspondence optimisation strategy. PMID- 25122837 TI - The lightweight Delft Cylinder Hand: first multi-articulating hand that meets the basic user requirements. AB - Rejection rates of upper limb prostheses are high (23%-45%). Amputees indicate that the highest design priority should be reduction of the mass of the prosthetic device. Despite all efforts, the mass of the new prosthetic hands is 35%-73% higher than that of older hands. Furthermore, current hands are thicker than a human hand, they operate slower and do not provide proprioceptive force and position feedback. This study presents the Delft Cylinder Hand, a body powered prosthetic hand which mass is 55%-68% lower than that of the lightest current prosthetic hands, operates faster, has an anthropomorphic shape, and provides proprioceptive force and position feedback. The hand has articulating fingers, actuated by miniature hydraulic cylinders. The articulating fingers adapt to the shape of the grasped object. Its functional scores are similar to that of current prosthetic devices. The hand has a higher mechanical performance than current body-powered hands. It requires 49%-162% less energy from the user and it can deliver a higher maximum pinch force (30-60 N). PMID- 25122836 TI - Hierarchy of neural organization in the embryonic spinal cord: Granger-causality graph analysis of in vivo calcium imaging data. AB - The recent development of genetically encoded calcium indicators enables monitoring in vivo the activity of neuronal populations. Most analysis of these calcium transients relies on linear regression analysis based on the sensory stimulus applied or the behavior observed. To estimate the basic properties of the functional neural circuitry, we propose a network approach to calcium imaging recorded at single cell resolution. Differently from previous analysis based on cross-correlation, we used Granger-causality estimates to infer information propagation between the activities of different neurons. The resulting functional network was then modeled as a directed graph and characterized in terms of connectivity and node centralities. We applied our approach to calcium transients recorded at low frequency (4 Hz) in ventral neurons of the zebrafish spinal cord at the embryonic stage when spontaneous coiling of the tail occurs. Our analysis on population calcium imaging data revealed a strong ipsilateral connectivity and a characteristic hierarchical organization of the network hubs that supported established propagation of activity from rostral to caudal spinal cord. Our method could be used for detecting functional defects in neuronal circuitry during development and pathological conditions. PMID- 25122838 TI - Theoretical modeling and experimental validation of surface stress in thrombin aptasensor. AB - Adsorption of target molecules on the immobilized microcantilever surface produced beam displacement due to the differential surface stress generated between the immobilized and non-immobilized surface. Surface stress is caused by the intermolecular forces between the molecules. Van der Waals, electrostatic forces, hydrogen bonding, hydrophobic effect and steric hindrance are some of the intermolecular forces involved. A theoretical framework describing the adsorption induced microcantilever displacement is derived in this paper. Experimental displacement of thrombin aptamer-thrombin interactions was carried out. The relation between the electrostatic interactions involved between adsorbates (thrombin) as well as adsorbates and substrates (thrombin aptamer) and the microcantilever beam displacement utilizing the proposed mathematical model was quantified and compared to the experimental value. This exercise is important to aid the designers in microcantilever sensing performance optimization. PMID- 25122839 TI - Measurement of intravenously administered gamma-Fe2O3 particle amount in mice tissues using vibrating sample magnetometer. AB - Dispersions of platelet gamma-Fe2O3 particles 30-50nm in size were intravenously administered to mice and the amount of particles accumulated in each tissue was obtained by magnetization measurement using a vibrating sample magnetometer. Background noise was greatly reduced by measuring dried tissues under a magnetic field of 500 Oe so that the effect of diamagnetism was slight. Remarkable particle accumulation was observed in the liver and spleen. Considerable particle accumulation was observed in the lung when a large quantity of gamma-Fe2 O3 particles was administered. There was no significant particle accumulation in the kidney and heart. PMID- 25122840 TI - Prediction of essential proteins based on overlapping essential modules. AB - Many computational methods have been proposed to identify essential proteins by using the topological features of interactome networks. However, the precision of essential protein discovery still needs to be improved. Researches show that majority of hubs (essential proteins) in the yeast interactome network are essential due to their involvement in essential complex biological modules and hubs can be classified into two categories: date hubs and party hubs. In this study, combining with gene expression profiles, we propose a new method to predict essential proteins based on overlapping essential modules, named POEM. In POEM, the original protein interactome network is partitioned into many overlapping essential modules. The frequencies and weighted degrees of proteins in these modules are employed to decide which categories does a protein belong to? The comparative results show that POEM outperforms the classical centrality measures: Degree Centrality (DC), Information Centrality (IC), Eigenvector Centrality (EC), Subgraph Centrality (SC), Betweenness Centrality (BC), Closeness Centrality (CC), Edge Clustering Coefficient Centrality (NC), and two newly proposed essential proteins prediction methods: PeC and CoEWC. Experimental results indicate that the precision of predicting essential proteins can be improved by considering the modularity of proteins and integrating gene expression profiles with network topological features. PMID- 25122841 TI - Biological analysis of Jeffrey nanofluid in a curved channel with heat dissipation. AB - This study examines the peristaltic flow of Jeffrey nanofluid in a curved channel. The governing equations of Jeffrey nanofluid model for curved channel are derived including the effects of curvature. The highly nonlinear partial differential equations are simplified by using the long wave length and low Reynolds number assumptions. The reduced nonlinear partial differential equations are solved analytically with the help of homotopy perturbation method. The expression for pressure rise is computed through numerical integration. The physical features of pertinent parameters have been discussed by plotting the graphs of pressure rise, velocity, temperature, nanoparticle volume fraction and stream functions. It is observed that the curve-ness of the channel decreases the pressure rise in the peristaltic pumping region. Moreover, curve-ness of the channel effects the fluid flow by decreasing the fluid velocity near inner wall and increasing the velocity near the outer wall of the channel. PMID- 25122842 TI - Blind image quality assessment via deep learning. AB - This paper investigates how to blindly evaluate the visual quality of an image by learning rules from linguistic descriptions. Extensive psychological evidence shows that humans prefer to conduct evaluations qualitatively rather than numerically. The qualitative evaluations are then converted into the numerical scores to fairly benchmark objective image quality assessment (IQA) metrics. Recently, lots of learning-based IQA models are proposed by analyzing the mapping from the images to numerical ratings. However, the learnt mapping can hardly be accurate enough because some information has been lost in such an irreversible conversion from the linguistic descriptions to numerical scores. In this paper, we propose a blind IQA model, which learns qualitative evaluations directly and outputs numerical scores for general utilization and fair comparison. Images are represented by natural scene statistics features. A discriminative deep model is trained to classify the features into five grades, corresponding to five explicit mental concepts, i.e., excellent, good, fair, poor, and bad. A newly designed quality pooling is then applied to convert the qualitative labels into scores. The classification framework is not only much more natural than the regression based models, but also robust to the small sample size problem. Thorough experiments are conducted on popular databases to verify the model's effectiveness, efficiency, and robustness. PMID- 25122843 TI - The Connection Between Bayesian Estimation of a Gaussian Random Field and RKHS. AB - Reconstruction of a function from noisy data is key in machine learning and is often formulated as a regularized optimization problem over an infinite dimensional reproducing kernel Hilbert space (RKHS). The solution suitably balances adherence to the observed data and the corresponding RKHS norm. When the data fit is measured using a quadratic loss, this estimator has a known statistical interpretation. Given the noisy measurements, the RKHS estimate represents the posterior mean (minimum variance estimate) of a Gaussian random field with covariance proportional to the kernel associated with the RKHS. In this brief, we provide a statistical interpretation when more general losses are used, such as absolute value, Vapnik or Huber. Specifically, for any finite set of sampling locations (that includes where the data were collected), the maximum a posteriori estimate for the signal samples is given by the RKHS estimate evaluated at the sampling locations. This connection establishes a firm statistical foundation for several stochastic approaches used to estimate unknown regularization parameters. To illustrate this, we develop a numerical scheme that implements a Bayesian estimator with an absolute value loss. This estimator is used to learn a function from measurements contaminated by outliers. PMID- 25122844 TI - Adaptive Output-Feedback Neural Control of Switched Uncertain Nonlinear Systems With Average Dwell Time. AB - This paper investigates the problem of adaptive neural tracking control via output-feedback for a class of switched uncertain nonlinear systems without the measurements of the system states. The unknown control signals are approximated directly by neural networks. A novel adaptive neural control technique for the problem studied is set up by exploiting the average dwell time method and backstepping. A switched filter and different update laws are designed to reduce the conservativeness caused by adoption of a common observer and a common update law for all subsystems. The proposed controllers of subsystems guarantee that all closed-loop signals remain bounded under a class of switching signals with average dwell time, while the output tracking error converges to a small neighborhood of the origin. As an application of the proposed design method, adaptive output feedback neural tracking controllers for a mass-spring-damper system are constructed. PMID- 25122845 TI - Discrete-Time Zhang Neural Network for Online Time-Varying Nonlinear Optimization With Application to Manipulator Motion Generation. AB - In this brief, a discrete-time Zhang neural network (DTZNN) model is first proposed, developed, and investigated for online time-varying nonlinear optimization (OTVNO). Then, Newton iteration is shown to be derived from the proposed DTZNN model. In addition, to eliminate the explicit matrix-inversion operation, the quasi-Newton Broyden-Fletcher-Goldfarb-Shanno (BFGS) method is introduced, which can effectively approximate the inverse of Hessian matrix. A DTZNN-BFGS model is thus proposed and investigated for OTVNO, which is the combination of the DTZNN model and the quasi-Newton BFGS method. In addition, theoretical analyses show that, with step-size h=1 and/or with zero initial error, the maximal residual error of the DTZNN model has an O(tau(2)) pattern, whereas the maximal residual error of the Newton iteration has an O(tau) pattern, with tau denoting the sampling gap. Besides, when h ? 1 and h ? (0,2) , the maximal steady-state residual error of the DTZNN model has an O(tau(2)) pattern. Finally, an illustrative numerical experiment and an application example to manipulator motion generation are provided and analyzed to substantiate the efficacy of the proposed DTZNN and DTZNN-BFGS models for OTVNO. PMID- 25122846 TI - Temporal and spatial monitoring and prediction of epidemic outbreaks. AB - This paper introduces a nonlinear dynamic model to study spatial and temporal dynamics of epidemics of susceptible-infected-removed type. It involves modeling the respective collections of epidemic states and syndromic observations as random finite sets. Each epidemic state consists of the number of infected individuals in an isolated population system and the corresponding partially known parameters of the epidemic model. The infectious disease could spread between population systems with known probabilities based on prior knowledge of ecological and biological features of the environment. The problem is then formulated in the context of Bayesian framework and estimated via a probability hypothesis density filter. Each population system under surveillance is assumed to be homogenous and fixed, with daily reports on the number of infected people available for monitoring and prediction. When model parameters are partially known, results of numerical studies indicate that the proposed approach can help early prediction of the epidemic in terms of peak and duration. PMID- 25122847 TI - Global asymptotic stabilization using adaptive fuzzy PD control. AB - It is well-known that standard adaptive fuzzy control (AFC) can only guarantee uniformly ultimately bounded stability due to inherent fuzzy approximation errors (FAEs). This paper proves that standard AFC with proportional-derivative (PD) control can guarantee global asymptotic stabilization even in the presence of FAEs for a class of uncertain affine nonlinear systems. Variable-gain PD control is designed to globally stabilize the plant. An optimal FAE is shown to be bounded by the norm of the plant state vector multiplied by a globally invertible and nondecreasing function, which provides a pivotal property for stability analysis. Without discontinuous control compensation, the closed-loop system achieves global and partially asymptotic stability in the sense that all plant states converge to zero. Compared with previous adaptive approximation-based global/asymptotic stabilization approaches, the major advantage of our approach is that global stability and asymptotic stabilization are achieved concurrently by a much simpler control law. Illustrative examples have further verified the theoretical results. PMID- 25122848 TI - On fuzzy sampled-data control of chaotic systems via a time-dependent Lyapunov functional approach. AB - In this paper, a novel approach to fuzzy sampled-data control of chaotic systems is presented by using a time-dependent Lyapunov functional. The advantage of the new method is that the Lyapunov functional is continuous at sampling times but not necessarily positive definite inside the sampling intervals. Compared with the existing works, the constructed Lyapunov functional makes full use of the information on the piecewise constant input and the actual sampling pattern. In terms of a new parameterized linear matrix inequality (LMI) technique, a less conservative stabilization condition is derived to guarantee the exponential stability for the closed-loop fuzzy sampled-data system. By solving a set of LMIs, the fuzzy sampled-data controller can be easily obtained. Finally, the chaotic Lorenz system and Rossler's system are employed to illustrate the feasibility and effectiveness of the proposed method. PMID- 25122849 TI - Feature selection in supervised saliency prediction. AB - There is an increasing interest in learning mappings from features to saliency maps based on human fixation data on natural images. These models have achieved better results than most bottom-up (unsupervised) saliency models. However, they usually use a large set of features trying to account for all possible saliency related factors, which increases time cost and leaves the truly effective features unknown. Through supervised feature selection, we show that the features used in existing models are highly redundant. On each of three benchmark datasets considered in this paper, a small number of features are found to be good enough for predicting human eye fixations in free viewing experiments. The resulting model achieves comparable results to that with all features and outperforms the state-of-the-art models on these datasets. In addition, both the features selected and the model trained on any dataset exhibit good performance on the other two datasets, indicating robustness of the selected features and models across different datasets. Finally, after training on a dataset for two different tasks, eye fixation prediction and salient object detection, the selected features show robustness across the two tasks. Taken together, these findings suggest that a small set of features could account for visual saliency. PMID- 25122850 TI - Model learning and knowledge sharing for a multiagent system with Dyna-Q learning. AB - In a multiagent system, if agents' experiences could be accessible and assessed between peers for environmental modeling, they can alleviate the burden of exploration for unvisited states or unseen situations so as to accelerate the learning process. Since how to build up an effective and accurate model within a limited time is an important issue, especially for complex environments, this paper introduces a model-based reinforcement learning method based on a tree structure to achieve efficient modeling and less memory consumption. The proposed algorithm tailored a Dyna-Q architecture to multiagent systems by means of a tree structure for modeling. The tree-model built from real experiences is used to generate virtual experiences such that the elapsed time in learning could be reduced. As well, this model is suitable for knowledge sharing. This paper is inspired by the concept of knowledge sharing methods in multiagent systems where an agent could construct a global model from scattered local models held by individual agents. Consequently, it can increase modeling accuracy so as to provide valid simulated experiences for indirect learning at the early stage of learning. To simplify the sharing process, the proposed method applies resampling techniques to grafting partial branches of trees containing required and useful experiences disseminated from experienced peers, instead of merging the whole trees. The simulation results demonstrate that the proposed sharing method can achieve the objectives of sample efficiency and learning acceleration in multiagent cooperation applications. PMID- 25122851 TI - A video, text, and speech-driven realistic 3-d virtual head for human-machine interface. AB - A multiple inputs-driven realistic facial animation system based on 3-D virtual head for human-machine interface is proposed. The system can be driven independently by video, text, and speech, thus can interact with humans through diverse interfaces. The combination of parameterized model and muscular model is used to obtain a tradeoff between computational efficiency and high realism of 3 D facial animation. The online appearance model is used to track 3-D facial motion from video in the framework of particle filtering, and multiple measurements, i.e., pixel color value of input image and Gabor wavelet coefficient of illumination ratio image, are infused to reduce the influence of lighting and person dependence for the construction of online appearance model. The tri-phone model is used to reduce the computational consumption of visual co articulation in speech synchronized viseme synthesis without sacrificing any performance. The objective and subjective experiments show that the system is suitable for human-machine interaction. PMID- 25122852 TI - Multilayer obstacle-avoiding x-architecture steiner minimal tree construction based on particle swarm optimization. AB - As the basic model for very large scale integration routing, the Steiner minimal tree (SMT) can be used in various practical problems, such as wire length optimization, congestion, and time delay estimation. In this paper, an effective algorithm based on particle swarm optimization is presented to construct a multilayer obstacle-avoiding X-architecture SMT (ML-OAXSMT). First, a pretreatment strategy is presented to reduce the total number of judgments for the routing conditions around obstacles and vias. Second, an edge transformation strategy is employed to make the particles have the ability to bypass the obstacles while the union-find partition is used to prevent invalid solutions. Third, according to the feature of ML-OAXSMT problem, we design an edge-vertex encoding strategy, which has the advantage of simple and effective. Moreover, a penalty mechanism is proposed to help the particle bypass the obstacles, and reduce the generation of via at the same time. Experimental results show that our algorithm from a global perspective of multilayer structure can achieve the best solution quality among the existing algorithms. Finally, to our best knowledge, we redefine the edge cost and then construct the obstacle-avoiding preferred direction X-architecture Steiner tree, which is the first work to address this problem and can offer the theory supports for chip design based on non-Manhattan architecture. PMID- 25122853 TI - Poor performance of the determine HIV-1/2 Ag/Ab combo fourth-generation rapid test for detection of acute infections in a National Household Survey in Swaziland. AB - Fourth-generation HIV rapid tests (RTs) claim to detect both p24 antigen (Ag) and HIV antibodies (Ab) for early identification of acute infections, important for targeting prevention and reducing HIV transmission. In a nationally representative household survey in Swaziland, 18,172 adults, age 18 to 49 years, received home-based HIV rapid testing in 2010 and 2011. Of the 18,172 individuals, 5,822 (32.0%) were Ab positive (Ab(+)) by the Determine HIV-1/2 Ab/Ab combo test, and 5,789 (99.4%) of those were confirmed to be reactive in the Uni-Gold test. Determine combo identified 12 individuals as having acute infections (Ag(+)/Ab negative [Ab(-)]); however, none had detectable HIV-1 RNA and 8 of 12 remained HIV negative at their 6-week follow-up visit (4 were lost to follow-up). All RT-nonreactive samples were pooled and tested by nucleic acid amplification testing (NAAT) to identify acute infections. NAAT identified 13 (0.1%) of the 12,338 HIV antibody-negative specimens as HIV RNA positive, with RNA levels ranging from 300 to >10,000,000 copies/ml. However, none of them were Ag(+) by Determine combo. Follow-up testing of 12 of the 13 NAAT-positive individuals at 6 months demonstrated 12 seroconversions (1 individual was lost to follow-up). Therefore, the Determine combo test had a sensitivity of 0% (95% confidence interval, 0 to 28) and positive predictive value of 0% for the detection of acute infections. The ability of the 4th-generation Determine combo to detect antigen was very poor in Swaziland. Thus, the Determine combo test does not add any value to the current testing algorithm; rather, it adds additional costs and complexity to HIV diagnosis. The detection of acute HIV infections may need to rely on other testing strategies. PMID- 25122855 TI - Comparison of flocked and aptima swabs and two specimen transport media in the aptima combo 2 assay. AB - Self-collected vaginal Aptima swabs and flocked swabs in Aptima specimen transport medium and ESwabs in ESwab medium detected all 37 Chlamydia trachomatis infected patients from 287 women tested by the Aptima Combo assay. Prevalence rates of C. trachomatis, Neisseria gonorrhoeae, and dual infection were 12.8%, 3.1%, and 2.4%, respectively. PMID- 25122856 TI - Mupirocin-induced mutations in ileS in various genetic backgrounds of methicillin resistant Staphylococcus aureus. AB - Topical mupirocin is widely used for the decolonization of methicillin-resistant Staphylococcus aureus (MRSA) carriers. We evaluated the capacity of various MRSA clonotypes to develop mutations in the ileS gene associated with low-level mupirocin resistance. Twenty-four mupirocin-sensitive MRSA isolates from a variety of genotypes (determined by a multilocus variable-number tandem-repeat assay) were selected. Mupirocin MICs were determined by Etest. The isolates were then incubated in subinhibitory concentrations of mupirocin for 7 to 14 days. Repeat MIC determinations and sequencing of the ileS gene were then performed. Doubling times of isolates exposed to mupirocin and of unexposed isolates were compared. We found that exposure to mupirocin led to rapid induction of low-level resistance (MICs of 8 to 24 MUg/ml) in 11 of 24 (46%) MRSA isolates. This phenomenon was observed in strains with diverse genetic backgrounds. Various mutations were detected in 18 of 24 (75%) MRSA isolates. Acquisition of mutations appeared to be a stepwise process during prolonged incubation with the drug. Among the five isolates exhibiting low-level resistance and the highest MICs, four tested sensitive after incubation in the absence of mupirocin but there was no reversion to the susceptible wild-type primary sequence. Resistance was not associated with significant fitness cost, suggesting that MRSA strains with low level mupirocin resistance may have a selective advantage in facilities where mupirocin is commonly used. Our findings emphasize the importance of the judicious use of this topical agent and the need to closely monitor for the emergence of resistance. PMID- 25122854 TI - PCR in diagnosis of invasive aspergillosis: a meta-analysis of diagnostic performance. AB - Invasive aspergillosis is a difficult-to-diagnose infection with a high mortality rate that affects high-risk groups such as patients with neutropenia and hematologic malignancies. We performed a bivariate meta-analysis of diagnostic data for an Aspergillus sp. PCR assay with blood specimens from high-risk hematology patients. We included all studies involving human subjects that assessed the performance of any PCR assay for invasive aspergillosis in whole blood or serum and that used the European Organization for the treatment of Cancer/Mycoses Study Group criteria as a reference standard. Three investigators independently searched the literature for eligible studies and extracted the data. Out of a total of 37 studies, 25 met strict quality criteria and were included in our evidence synthesis. Twenty-five studies with 2,595 patients were analyzed. The pooled diagnostic performance of whole-blood and serum PCR assays was moderate, with a sensitivity and specificity of 84% (95% confidence interval [CI], 75 to 91%) and 76% (95% CI, 65 to 84%), respectively, suggesting that a positive or negative result is unable, on its own, to confirm or exclude a suspected infection. The performance of a PCR assay of serum was not significantly different from that of whole blood. Notably, at least two positive PCR test results were found to have a specificity of 95% and a sensitivity of 64% for invasive infection, achieving a high positive likelihood ratio of 12.8. Importantly, the European Aspergillus PCR Initiative (EAPCRI) recommendations improved the performance of the PCR even further when at least two positive specimens were used to define PCR positivity. In conclusion, two positive PCR results should be considered highly indicative of an active Aspergillus sp. infection. Use of the EAPCRI recommendations by clinical laboratories can further enhance PCR performance. PMID- 25122857 TI - Evaluation of the nanosphere Verigene BC-GN assay for direct identification of gram-negative bacilli and antibiotic resistance markers from positive blood cultures and potential impact for more-rapid antibiotic interventions. AB - The Verigene BC-GN assay correctly identified all 51 Gram-negative bacilli (GNB) from positive blood cultures and all 14 carbapenemase enzymes tested. The assay gave organism identification (ID) results an average of 24 h faster compared to conventional identifications. Medical management could have been modified for 31.8% of patients an average 33 h sooner. In conclusion, the BC-GN assay is a very accurate, rapid assay which would allow for more-immediate medical management decisions in patients with bacteremia from GNB. PMID- 25122858 TI - Two cases of bacteriemia caused by nontoxigenic, non-O1, non-O139 Vibrio cholerae isolates in Ho Chi Minh City, Vietnam. AB - The toxigenic bacterium Vibrio cholerae belonging to the O1 and O139 serogroups is commonly associated with epidemic diarrhea in tropical settings; other diseases caused by this environmental pathogen are seldom identified. Here we report two unassociated cases of nonfatal, nontoxigenic V. cholerae non-O1, non O139 bacteremia in patients with comorbidities in Ho Chi Minh City, Vietnam, that occurred within a 4-week period. PMID- 25122860 TI - Generation of calves persistently infected with HoBi-like pestivirus and comparison of methods for detection of these persistent infections. AB - The identification and elimination of persistently infected (PI) cattle are the most effective measures for controlling bovine pestiviruses, including bovine viral diarrhea virus (BVDV) and the emerging HoBi-like viruses. Here, colostrum deprived calves persistently infected with HoBi-like pestivirus (HoBi-like PI calves) were generated and sampled (serum, buffy coat, and ear notches) on the day of birth (DOB) and weekly for 5 consecutive weeks. The samples were subjected to diagnostic tests for BVDV--two reverse transcriptase PCR (RT-PCR) assays, two commercial real-time RT quantitative PCR (RT-qPCR), two antigen capture enzyme linked immunosorbent assays (ACE), and immunohistochemistry (IHC)--and to HoBi like virus-specific RT-PCR and RT-qPCR assays. The rate of false negatives varied among the calves. The HoBi-like virus-specific RT-PCR detected HoBi-like virus in 83%, 75%, and 87% of the serum, buffy coat, and ear notch samples, respectively, while the HoBi-like RT-qPCR detected the virus in 83%, 96%, and 62%, respectively. In comparison, the BVDV RT-PCR test had a higher rate of false negatives in all tissue types, especially for the ear notch samples (missing detection in at least 68% of the samples). The commercial BVDV RT-qPCRs and IHC detected 100% of the ear notch samples as positive. While ACE based on the BVDV glycoprotein E(rns) detected infection in at least 87% of ear notches, no infections were detected using NS3-based ACE. The BVDV RT-qPCR, ACE, and IHC yielded higher levels of detection than the HoBi-like virus-specific assays, although the lack of differentiation between BVDV and HoBi-like viruses would make these tests of limited use for the control and/or surveillance of persistent HoBi-like virus infection. An improvement in HoBi-like virus tests is required before a reliable HoBi-like PI surveillance program can be designed. PMID- 25122859 TI - Laboratory detection of Clostridium difficile in piglets in Australia. AB - Clostridium difficile is a well-known enteric pathogen of humans and the causative agent of high-morbidity enteritis in piglets aged 1 to 7 days. C. difficile prevalence in Australian piglets is as high as 70%. The current diagnostic assays have been validated only for human infections, and there are no published studies assessing their performance in Australian piglets. We evaluated the suitability of five assays for detecting C. difficile in 157 specimens of piglet feces. The assays included a loop-mediated isothermal amplification (LMIA) PCR for tcdA (illumigene C. difficile; Meridian), a real-time PCR for tcdB (GeneOhm Cdiff; Becton Dickinson), two-component enzyme immunoassays (EIA) for C. difficile glutamate dehydrogenase (GDH) (EIA-GDH) and TcdA/TcdB (EIA-TcdA/TcdB) (C. diff Quik Chek; Alere), and direct culture (DC) (C. difficile chromID agar; bioMerieux). The assays for detection of the organism were compared against enrichment culture (EC), and assays for detection of toxins/toxin genes were compared against EC followed by PCR for toxin genes (toxigenic EC [TEC]). The recovery of C. difficile by EC was 39.5% (n = 62/157), and TEC revealed that 58.1% (n = 36/62) of isolates were positive for at least one toxin gene (tcdA/tcdB). Compared with those for EC/TEC, the sensitivities, specificities, positive predictive values, and negative predictive values were, respectively, as follows: DC, 91.9, 100.0, 100.0, and 95.0%; EIA-GDH, 41.9, 92.6, 78.8, and 71.0%; EIA-TcdA/TcdB, 5.6, 99.2, 66.7, and 77.9%; real-time PCR, 42.9, 96.7, 78.9, and 85.4% and LMIA-PCR, 25.0, 95.9, 64.3, and 81.1%. The performance of the molecular methods was poor, suggesting that the current commercially available assays for diagnosis of C. difficile in humans are not suitable for use in piglets. C. difficile recovery by the DC provides a cost-effective alternative. PMID- 25122861 TI - Comparative evaluation of three commercial systems for detection of high-risk human papillomavirus in cervical and vaginal ThinPrep PreservCyt samples and correlation with biopsy results. AB - Genital human papillomavirus (HPV) is the etiologic agent of more than 99% of all cervical cancers worldwide, with 14 genotypes being considered oncogenic or "high risk" because of their association with severe dysplasia and cervical carcinoma. Among these 14 high-risk types, HPV-16 and -18 account for approximately 70% of cervical cancers. The aim of this study was to evaluate three FDA-approved HPV nucleic acid-based tests for the ability to predict high-grade cervical intraepithelial neoplasias (CIN2 or worse) in corresponding tissue biopsy specimens. Residual specimens (total n = 793, cervical n = 743, vaginal n = 50) collected in ThinPrep PreservCyt medium with a cytologic result of >= atypical squamous cells of undetermined significance were tested by the Hybrid Capture 2 (HC2) assay (Qiagen, Gaithersburg, MD), the cobas HPV test (Roche Diagnostics, Indianapolis, IN), and the APTIMA HPV assay (Hologic, San Diego, CA). Genotyping for HPV-16 and HPV-18 was simultaneously performed by the cobas HPV test. Results were compared to cervical or vaginal biopsy findings, when they were available (n = 350). Among the 350 patients with corresponding biopsy results, 81 (23.1%) showed >= CIN2 by histopathology. The >= CIN2 detection sensitivity was 91.4% by the cobas and APTIMA assays and 97.5% by HC2 assay. The specificities of the cobas, APTIMA, and HC2 assays were 31.2, 42.0, and 27.1%, respectively. When considering only positive HPV-16 and/or HPV-18 genotype results, the cobas test showed a sensitivity and a specificity of 51.9 and 86.6%, respectively. While the HC2, cobas, and APTIMA assays showed similar sensitivities for the detection of >= CIN2 lesions, the specificities of the three tests varied, with the greatest specificity (86.6%) observed when the HPV-16 and/or HPV-18 genotypes were detected. PMID- 25122863 TI - Evaluation of disk potentiation test using kirby-bauer disks containing high dosage fosfomycin and glucose-6-phosphate to detect production of glutathione S transferase responsible for fosfomycin resistance. PMID- 25122862 TI - Collection and characterization of samples for establishment of a serum repository for lyme disease diagnostic test development and evaluation. AB - Serological assays and a two-tiered test algorithm are recommended for laboratory confirmation of Lyme disease. In the United States, the sensitivity of two-tiered testing using commercially available serology-based assays is dependent on the stage of infection and ranges from 30% in the early localized disease stage to near 100% in late-stage disease. Other variables, including subjectivity in reading Western blots, compliance with two-tiered recommendations, use of different first- and second-tier test combinations, and use of different test samples, all contribute to variation in two-tiered test performance. The availability and use of sample sets from well-characterized Lyme disease patients and controls are needed to better assess the performance of existing tests and for development of improved assays. To address this need, the Centers for Disease Control and Prevention and the National Institutes of Health prospectively collected sera from patients at all stages of Lyme disease, as well as healthy donors and patients with look-alike diseases. Patients and healthy controls were recruited using strict inclusion and exclusion criteria. Samples from all included patients were retrospectively characterized by two-tiered testing. The results from two-tiered testing corroborated the need for novel and improved diagnostics, particularly for laboratory diagnosis of earlier stages of infection. Furthermore, the two-tiered results provide a baseline with samples from well-characterized patients that can be used in comparing the sensitivity and specificity of novel diagnostics. Panels of sera and accompanying clinical and laboratory testing results are now available to Lyme disease serological test users and researchers developing novel tests. PMID- 25122864 TI - Predictive value of testing nasopharyngeal samples for respiratory viruses in the setting of lower respiratory tract disease. AB - To determine the predictive value of nasopharyngeal (NP) sample testing for respiratory viruses (RVs) in suspected lower respiratory tract disease, 72 paired NP and bronchoalveolar lavage (BAL) fluid specimen sets, mostly from transplant recipients or patients with hematologic malignancies, were analyzed. Overall, 31.3% of the specimens tested positive for an RV. In 19 sets (26.4%), the NP and BAL fluid specimens were both positive for an RV; in 3 sets (4.2%), the NP specimens were positive but the BAL fluid specimens were negative; and in 3 other sets, the NP specimens were negative but the BAL fluid specimens were positive. The positive and negative predictive values of the NP specimens were 86.4% and 94%, respectively. PMID- 25122865 TI - Mutational analysis of Pneumocystis jirovecii dihydropteroate synthase and dihydrofolate reductase genes in HIV-infected patients in China. AB - We investigated Pneumocystis jirovecii dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) genes for mutations in 25 Chinese HIV-infected patients with P. jirovecii pneumonia. We identified DHPS mutations in 3 (12%) patients and DHFR mutations in 1 (4%) patient. The prevalence of DHPS and DHFR mutations in China remains low, as it does in other developing countries. PMID- 25122866 TI - Clinical characteristics of patients who test positive for Clostridium difficile by repeat PCR. AB - The high sensitivity of PCR assays for diagnosing Clostridium difficile infection (CDI) has greatly reduced the need for repeat testing after a negative result. Nevertheless, a small subset of patients do test positive within 7 days of a negative test. The aim of this study was to evaluate the clinical characteristics of these patients to determine when repeat testing may be appropriate. The results of all Xpert C. difficile PCR (Cepheid, Sunnyvale CA) tests performed in the clinical microbiology laboratory at New York-Presbyterian Hospital, Columbia University Medical Center (NYPH/CUMC) from 1 May 2011 through 6 September 2013, were reviewed. A retrospective case-control study was performed, comparing patients who tested positive within 7 days of a negative test result to a random selection of 50 controls who tested negative within 7 days of a negative test result. During the study period, a total of 14,875 tests were performed, of which 1,066 were repeat tests (7.2%). Eleven of these repeat tests results were positive (1.0%). The only risk factor independently associated with repeat testing positive was history of a prior CDI (odds ratio [OR], 19.6 [95% confidence interval {CI}, 4.0 to 19.5], P < 0.001). We found that patients who test positive for C. difficile by PCR within 7 days of a negative test are more likely to have a history of CDI than are patients who test negative with repeat PCR. This finding may be due to the high rate of disease relapse or the increased likelihood of empirical therapy leading to false-negative results in these patients. PMID- 25122867 TI - Systematic review of health outcomes in relation to salt intake highlights the widening divide between guidelines and the evidence. PMID- 25122868 TI - Sodium and cardiovascular disease: what the data show. PMID- 25122869 TI - Graudal et al. article on sodium intake should include ethnic disclaimer. PMID- 25122870 TI - Response to "Article on sodium intake should include ethnic disclaimer". PMID- 25122875 TI - The central importance of the cytoskeleton for increased cell stiffness in cardiovascular disease. Focus on "Diabetes increases stiffness of live cardiomyocytes measured by atomic force microscopy nanoindentation". PMID- 25122874 TI - Biomechanical strain vehicles for fibroblast-directed skeletal myoblast differentiation and myotube functionality in a novel coculture. AB - Skeletal muscle functionality is governed by multiple stimuli, including cytokines and biomechanical strain. Fibroblasts embedded within muscle connective tissue respond to biomechanical strain by secreting cytokines that induce myoblast differentiation and, we hypothesize, regulate myotube function. A coculture was established to allow cross talk between fibroblasts in Bioflex wells and myoblasts on nondeformable coverslips situated above Bioflex wells. Cyclic short-duration strain (CSDS) modeling repetitive stress/injury, acyclic long-duration strain (ALDS) modeling manipulative therapy, and combined strain paradigms (CSDS + ALDS) were applied to fibroblasts. Nonstrained myoblasts in uniculture and coculture served as controls. After fibroblasts had induced myoblast differentiation, myotube contraction was assessed by perfusion of ACh (10(-11)-10(-3) M). CSDS-treated fibroblasts increased myotube contractile sensitivity vs. uniculture (P < 0.05). As contraction is dependent on ACh binding, expression and clustering of nicotinic ACh receptors (nAChRs) were measured. CSDS-treated fibroblasts increased nAChR expression (P < 0.05), which correlated with myotube contraction. ALDS-treated fibroblasts did not significantly affect contraction or nAChR expression. Agrin-treated myotubes were then used to design a computer algorithm to identify alpha-bungarotoxin-stained nAChR clusters. ALDS-treated fibroblasts increased nAChR clustering (P < 0.05), while CSDS-treated fibroblasts disrupted cluster formation. CSDS-treated fibroblasts produced nAChRs preferentially located in nonclustered regions (P < 0.05). Strain-activated fibroblasts mediate myotube differentiation with multiple functional phenotypes. Similar to muscle injury, CSDS-treated fibroblasts disrupted nAChR clusters and hypersensitized myotube contraction, while ALDS treated fibroblasts aggregated nAChRs in large clusters, which may have important clinical implications. Cellular strategies aimed at improving muscle functionality, such as through biomechanical strain vehicles that activate fibroblasts to stabilize postsynaptic nAChRs on nearby skeletal muscle, may serve as novel targets in neuromuscular disorders. PMID- 25122877 TI - Making the cut: analytical and empirical bioethics. PMID- 25122878 TI - Surgical castration, coercive offers and coercive effects: it is still not about consent. PMID- 25122880 TI - Understanding the basis of antibiotic resistance: a platform for drug discovery. AB - There are numerous genes in Salmonella enterica serovar Typhimurium that can confer resistance to fluoroquinolone antibiotics, including those that encode topoisomerase proteins, the primary targets of this class of drugs. However, resistance is often multifactorial in clinical isolates and it is not uncommon to also detect mutations in genes that affect the expression of proteins involved in permeability and multi-drug efflux. The latter mechanism, mediated by tripartite efflux systems, such as that formed by the AcrAB-TolC system, confers inherent resistance to many antibiotics, detergents and biocides. Genetic inactivation of efflux genes gives multi-drug hyper-susceptibility, and in the absence of an intact AcrAB-TolC system some chromosomal and transmissible antibiotic resistance genes no longer confer clinically relevant levels of resistance. Furthermore, a functional multi-drug resistance efflux pump, such as AcrAB-TolC, is required for virulence and the ability to form a biofilm. In part, this is due to altered expression of virulence and biofilm genes being sensitive to efflux status. Efflux pump expression can be increased, usually due to mutations in regulatory genes, and this confers resistance to clinically useful drugs such as fluoroquinolones and beta-lactams. Here, I discuss some of the work my team has carried out characterizing the mechanisms of antibiotic resistance in Salmonella enterica serovar Typhimurium from the late 1980s to 2014. A video of this Prize Lecture, presented at the Society for General Microbiology Annual Conference 2014, can be viewed via this link: https://www.youtube.com/watch?v=MCRumMV99Yw. PMID- 25122881 TI - Toward a better understanding of the injured hippocampus: multimodal imaging in functionally relevant substructures. PMID- 25122876 TI - ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that contributes to fibrotic remodeling. AB - Genesis of myofibroblasts is obligatory for the development of pathology in many adult lung diseases. Adult lung tissue contains a population of perivascular ABCG2(pos) mesenchymal stem cells (MSC) that are precursors of myofibroblasts and distinct from NG2 pericytes. We hypothesized that these MSC participate in deleterious remodeling associated with pulmonary fibrosis (PF) and associated hypertension (PH). To test this hypothesis, resident lung MSC were quantified in lung samples from control subjects and PF patients. ABCG2(pos) cell numbers were decreased in human PF and interstitial lung disease compared with control samples. Genetic labeling of lung MSC in mice enabled determination of terminal lineage and localization of ABCG2 cells following intratracheal administration of bleomycin to elicit fibrotic lung injury. Fourteen days following bleomycin injury enhanced green fluorescent protein (eGFP)-labeled lung MSC-derived cells were increased in number and localized to interstitial areas of fibrotic and microvessel remodeling. Finally, gene expression analysis was evaluated to define the response of MSC to bleomycin injury in vivo using ABCG2(pos) MSC isolated during the inflammatory phase postinjury and in vitro bleomycin or transforming growth factor-beta1 (TGF-beta1)-treated cells. MSC responded to bleomycin treatment in vivo with a profibrotic gene program that was not recapitulated in vitro with bleomycin treatment. However, TGF-beta1 treatment induced the appearance of a profibrotic myofibroblast phenotype in vitro. Additionally, when exposed to the profibrotic stimulus, TGF-beta1, ABCG2, and NG2 pericytes demonstrated distinct responses. Our data highlight ABCG2(pos) lung MSC as a novel cell population that contributes to detrimental myofibroblast-mediated remodeling during PF. PMID- 25122882 TI - Evolutionarily conserved mechanisms in calcium handling may underlie intrinsic sensitivity to dopaminergic neuron death. PMID- 25122885 TI - Electrophysiological correlates of voice learning and recognition. AB - Listeners can recognize familiar human voices from variable utterances, suggesting the acquisition of speech-invariant voice representations during familiarization. However, the neurocognitive mechanisms mediating learning and recognition of voices from natural speech are currently unknown. Using electrophysiology, we investigated how representations are formed during intentional learning of initially unfamiliar voices that were later recognized among novel voices. To probe the acquisition of speech-invariant voice representations, we compared a "same sentence" condition, in which speakers repeated the study utterances at test, and a "different sentence" condition. Although recognition performance was higher for same compared with different sentences, substantial voice learning also occurred for different sentences, with recognition performance increasing across consecutive study-test-cycles. During study, event-related potentials elicited by voices subsequently remembered elicited a larger sustained parietal positivity (~250-1400 ms) compared with subsequently forgotten voices. This difference due to memory was unaffected by test sentence condition and may thus reflect the acquisition of speech-invariant voice representations. At test, voices correctly classified as "old" elicited a larger late positive component (300-700 ms) at Pz than voices correctly classified as "new." This event-related potential OLD/NEW effect was limited to the same sentence condition and may thus reflect speech-dependent retrieval of voices from episodic memory. Importantly, a speech-independent effect for learned compared with novel voices was found in beta band oscillations (16-17 Hz) between 290 and 370 ms at central and right temporal sites. Our results are a first step toward elucidating the electrophysiological correlates of voice learning and recognition. PMID- 25122883 TI - Damage to the Salience Network and interactions with the Default Mode Network. AB - Interactions between the Salience Network (SN) and the Default Mode Network (DMN) are thought to be important for cognitive control. However, evidence for a causal relationship between the networks is limited. Previously, we have reported that traumatic damage to white matter tracts within the SN predicts abnormal DMN function. Here we investigate the effect of this damage on network interactions that accompany changing motor control. We initially used fMRI of the Stop Signal Task to study response inhibition in humans. In healthy subjects, functional connectivity (FC) between the right anterior insula (rAI), a key node of the SN, and the DMN transiently increased during stopping. This change in FC was not seen in a group of traumatic brain injury (TBI) patients with impaired cognitive control. Furthermore, the amount of SN tract damage negatively correlated with FC between the networks. We confirmed these findings in a second group of TBI patients. Here, switching rather than inhibiting a motor response: (1) was accompanied by a similar increase in network FC in healthy controls; (2) was not seen in TBI patients; and (3) tract damage after TBI again correlated with FC breakdown. This shows that coupling between the rAI and DMN increases with cognitive control and that damage within the SN impairs this dynamic network interaction. This work provides compelling evidence for a model of cognitive control where the SN is involved in the attentional capture of salient external stimuli and signals the DMN to reduce its activity when attention is externally focused. PMID- 25122886 TI - An amplitude modulation/demodulation scheme for whisker-based texture perception. AB - Whisking rodents can discriminate finely textured objects using their vibrissae. The biomechanical and neural processes underlying such sensory tasks remain elusive. Here we combine the use of model micropatterned substrates and high resolution videography of rats' whiskers during tactile exploration to study how texture information is mechanically encoded in the whisker motion. A biomechanical modeling of the whisker is developed, which yields quantitative predictions of the spectral and temporal characteristics of the observed whisker kinetics, for any given topography. These texture-induced whisker vibrations are then replayed via a multiwhisker stimulator while recording neuronal responses in the barrel field of the primary somatosensory cortex (S1bf). These results provide a comprehensive description of the transduction process at play during fine texture sensing in rats. They suggest that the sensory system operates through a vibratory amplitude modulation/demodulation scheme. Fine textural properties are encoded in the time-varying envelope of the whisker-resonant vibrations. This quantity is then recovered by neural demodulation, as it effectively drives the spiking-rate signal of a large fraction of S1 cortical neurons. This encoding/decoding scheme is shown to be robust against variations in exploratory conditions, such as the scanning speed or pad-to-substrate distance, thus allowing for reliable tactile discrimination in realistic conditions. PMID- 25122884 TI - Synaptic GluN2A and GluN2B containing NMDA receptors within the superficial dorsal horn activated following primary afferent stimulation. AB - NMDA receptors are important elements in pain signaling in the spinal cord dorsal horn. They are heterotetramers, typically composed of two GluN1 and two of four GluN2 subunits: GluN2A-2D. Mice lacking some of the GluN2 subunits show deficits in pain transmission yet functional synaptic localization of these receptor subtypes in the dorsal horn has not been fully resolved. In this study, we have investigated the composition of synaptic NMDA receptors expressed in monosynaptic and polysynaptic pathways from peripheral sensory fibers to lamina I neurons in rats. We focused on substance P receptor-expressing (NK1R+) projection neurons, critical for expression of hyperalgesia and allodynia. EAB-318 and (R)-CPP, GluN2A/B antagonists, blocked both monosynaptic and polysynaptic NMDA EPSCs initiated by primary afferent activation by ~90%. Physiological measurements exploiting the voltage dependence of monosynaptic EPSCs similarly indicated dominant expression of GluN2A/B types of synaptic NMDA receptors. In addition, at synapses between C fibers and NK1R+ neurons, NMDA receptor activation initiated a secondary, depolarizing current. Ifenprodil, a GluN2B antagonist, caused modest suppression of monosynaptic NMDA EPSC amplitudes, but had a widely variable, sometimes powerful, effect on polysynaptic responses following primary afferent stimulation when inhibitory inputs were blocked to mimic neuropathic pain. We conclude that GluN2B subunits are moderately expressed at primary afferent synapses on lamina I NK1R+ neurons, but play more important roles for polysynaptic NMDA EPSCs driven by primary afferents following disinhibition, supporting the view that the analgesic effect of the GluN2B antagonist on neuropathic pain is at least in part, within the spinal cord. PMID- 25122887 TI - Deep brain stimulation abolishes slowing of reactions to unlikely stimuli. AB - The cortico-basal-ganglia circuit plays a critical role in decision making on the basis of probabilistic information. Computational models have suggested how this circuit could compute the probabilities of actions being appropriate according to Bayes' theorem. These models predict that the subthalamic nucleus (STN) provides feedback that normalizes the neural representation of probabilities, such that if the probability of one action increases, the probabilities of all other available actions decrease. Here we report the results of an experiment testing a prediction of this theory that disrupting information processing in the STN with deep brain stimulation should abolish the normalization of the neural representation of probabilities. In our experiment, we asked patients with Parkinson's disease to saccade to a target that could appear in one of two locations, and the probability of the target appearing in each location was periodically changed. When the stimulator was switched off, the target probability affected the reaction times (RT) of patients in a similar way to healthy participants. Specifically, the RTs were shorter for more probable targets and, importantly, they were longer for the unlikely targets. When the stimulator was switched on, the patients were still faster for more probable targets, but critically they did not increase RTs as the target was becoming less likely. This pattern of results is consistent with the prediction of the model that the patients on DBS no longer normalized their neural representation of prior probabilities. We discuss alternative explanations for the data in the context of other published results. PMID- 25122888 TI - Exocytotic machineries of vestibular type I and cochlear ribbon synapses display similar intrinsic otoferlin-dependent Ca2+ sensitivity but a different coupling to Ca2+ channels. AB - The hair cell ribbon synapses of the mammalian auditory and vestibular systems differ greatly in their anatomical organization and firing properties. Notably, vestibular Type I hair cells (VHC-I) are surrounded by a single calyx-type afferent terminal that receives input from several ribbons, whereas cochlear inner hair cells (IHCs) are contacted by several individual afferent boutons, each facing a single ribbon. The specificity of the presynaptic molecular mechanisms regulating transmitter release at these different sensory ribbon synapses is not well understood. Here, we found that exocytosis during voltage activation of Ca(2+) channels displayed higher Ca(2+) sensitivity, 10 mV more negative half-maximum activation, and a smaller dynamic range in VHC-I than in IHCs. VHC-I had a larger number of Ca(2+) channels per ribbon (158 vs 110 in IHCs), but their Ca(2+) current density was twofold smaller because of a smaller open probability and unitary conductance. Using confocal and stimulated emission depletion immunofluorescence microscopy, we showed that VHC-I had fewer synaptic ribbons (7 vs 17 in IHCs) to which Cav1.3 channels are more tightly organized than in IHCs. Gradual intracellular Ca(2+) uncaging experiments revealed that exocytosis had a similar intrinsic Ca(2+) sensitivity in both VHC-I and IHCs (KD of 3.3 +/- 0.6 MUM and 4.0 +/- 0.7 MUM, respectively). In otoferlin-deficient mice, exocytosis was largely reduced in VHC-I and IHCs. We conclude that VHC-I and IHCs use a similar micromolar-sensitive otoferlin Ca(2+) sensor and that their sensory encoding specificity is essentially determined by a different functional organization of Ca(2+) channels at their synaptic ribbons. PMID- 25122889 TI - Sensory-evoked and spontaneous gamma and spindle bursts in neonatal rat motor cortex. AB - Self-generated neuronal activity originating from subcortical regions drives early spontaneous motor activity, which is a hallmark of the developing sensorimotor system. However, the neural activity patterns and role of primary motor cortex (M1) in these early movements are still unknown. Combining voltage sensitive dye imaging (VSDI) with simultaneous extracellular multielectrode recordings in postnatal day 3 (P3)-P5 rat primary somatosensory cortex (S1) and M1 in vivo, we observed that tactile forepaw stimulation induced spindle bursts in S1 and gamma and spindle bursts in M1. Approximately 40% of the spontaneous gamma and spindle bursts in M1 were driven by early motor activity, whereas 23.7% of the M1 bursts triggered forepaw movements. Approximately 35% of the M1 bursts were uncorrelated to movements and these bursts had significantly fewer spikes and shorter burst duration. Focal electrical stimulation of layer V neurons in M1 mimicking physiologically relevant 40 Hz gamma or 10 Hz spindle burst activity reliably elicited forepaw movements. We conclude that M1 is already involved in somatosensory information processing during early development. M1 is mainly activated by tactile stimuli triggered by preceding spontaneous movements, which reach M1 via S1. Only a fraction of M1 activity transients trigger motor responses directly. We suggest that both spontaneously occurring and sensory evoked gamma and spindle bursts in M1 contribute to the maturation of corticospinal and sensorimotor networks required for the refinement of sensorimotor coordination. PMID- 25122890 TI - High-NaCl perception in Drosophila melanogaster. AB - Salt is a fundamental nutrient that is required for many physiological processes, including electrolyte homeostasis and neuronal activity. In mammals and Drosophila, the detection of NaCl induces two different behaviors: low-salt concentrations provide an attractive stimulus, whereas high-salt concentrations are avoided. We identified the gene called serrano (sano) as being expressed in the sensory organs of Drosophila larvae. A transgenic reporter line showed that sano was coexpressed with Gr66a in a subset of gustatory neurons in the terminal organ of third-instar larvae. The disruption of sano gene expression in gustatory neurons led to the specific loss of high-salt concentration avoidance in larvae, whereas the detection of other attractive or aversive substances was unaffected. Moreover, using a cellular marker sensitive to calcium levels, Sano function was shown to be required for neuronal activity in response to high-salt concentrations. In these neurons, the loss of the DEG/ENaC channel PPK19 function also eliminated the cellular response to high-salt concentrations. Our study revealed that PPK19 and Sano are required in the neurons of the larval gustatory organs for the detection of high-salt concentrations. PMID- 25122891 TI - NMDA spike/plateau potentials in dendrites of thalamocortical neurons. AB - Dendritic NMDA spike/plateau potentials, first discovered in cortical pyramidal neurons, provide supralinear integration of synaptic inputs on thin and distal dendrites, thereby increasing the impact of these inputs on the soma. The more specific functional role of these potentials has been difficult to clarify, partly due to the complex circuitry of cortical neurons. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus participate in simpler circuits. They receive their primary afferent input from retina and send their output to visual cortex. Cortex, in turn, regulates this output through massive feedback to distal dendrites of the TC neurons. The TC neurons can operate in two modes related to behavioral states: burst mode prevailing during sleep, when T-type calcium bursts largely disrupt the transfer of signals from retina to cortex, and tonic mode, which provides reliable transfer of retinal signals to cortex during wakefulness. We studied dendritic potentials in TC neurons with combined two photon calcium imaging and whole-cell recording of responses to local dendritic glutamate iontophoresis in acute brain slices from mice. We found that NMDA spike/plateaus can be elicited locally at distal dendrites of TC neurons. We suggest that these dendritic potentials have important functions in the cortical regulation of thalamocortical transmission. NMDA spike/plateaus can induce shifts in the functional mode from burst to tonic by blockade of T-type calcium conductances. Moreover, in tonic mode, they can facilitate the transfer of retinal signals to cortex by depolarization of TC neurons. PMID- 25122892 TI - Human and monkey striatal interneurons are derived from the medial ganglionic eminence but not from the adult subventricular zone. AB - In adult rodent and monkey brains, newly born neurons in the subventricular zone (SVZ) in the wall of the lateral ventricle migrate into the olfactory bulb (OB) via the rostral migratory stream (RMS). A recent study reported that interneurons are constantly generating in the adult human striatum from the SVZ. In contrast, by taking advantage of the continuous expression of Sp8 from the neuroblast stage through differentiation into mature interneurons, we found that the adult human SVZ does not generate new interneurons for the striatum. In the adult human SVZ and RMS, very few neuroblasts were observed, and most of them expressed the transcription factor Sp8. Neuroblasts in the adult rhesus monkey SVZ-RMS-OB pathway also expressed Sp8. In addition, we observed that Sp8 was expressed by most adult human and monkey OB interneurons. However, very few Sp8+ cells were in the adult human striatum. This suggests that neuroblasts in the adult human SVZ and RMS are likely destined for the OB, but not for the striatum. BrdU-labeling results also revealed few if any newly born neurons in the adult rhesus monkey striatum. Finally, on the basis of transcription factor expression, we provide strong evidence that the vast majority of interneurons in the human and monkey striatum are generated from the medial ganglionic eminence during embryonic developmental stages, as they are in rodents. We conclude that, although a small number of neuroblasts exist in the adult human SVZ, they do not migrate into the striatum and become mature striatal interneurons. PMID- 25122894 TI - Size and synchronization of auditory cortex promotes musical, literacy, and attentional skills in children. AB - Playing a musical instrument is associated with numerous neural processes that continuously modify the human brain and may facilitate characteristic auditory skills. In a longitudinal study, we investigated the auditory and neural plasticity of musical learning in 111 young children (aged 7-9 y) as a function of the intensity of instrumental practice and musical aptitude. Because of the frequent co-occurrence of central auditory processing disorders and attentional deficits, we also tested 21 children with attention deficit (hyperactivity) disorder [AD(H)D]. Magnetic resonance imaging and magnetoencephalography revealed enlarged Heschl's gyri and enhanced right-left hemispheric synchronization of the primary evoked response (P1) to harmonic complex sounds in children who spent more time practicing a musical instrument. The anatomical characteristics were positively correlated with frequency discrimination, reading, and spelling skills. Conversely, AD(H)D children showed reduced volumes of Heschl's gyri and enhanced volumes of the plana temporalia that were associated with a distinct bilateral P1 asynchrony. This may indicate a risk for central auditory processing disorders that are often associated with attentional and literacy problems. The longitudinal comparisons revealed a very high stability of auditory cortex morphology and gray matter volumes, suggesting that the combined anatomical and functional parameters are neural markers of musicality and attention deficits. Educational and clinical implications are considered. PMID- 25122893 TI - Ribosome profiling reveals a cell-type-specific translational landscape in brain tumors. AB - Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5'-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. PMID- 25122895 TI - VGluT1+ neuronal glutamatergic signaling regulates postnatal developmental maturation of cortical protoplasmic astroglia. AB - Functional maturation of astroglia is characterized by the development of a unique, ramified morphology and the induction of important functional proteins, such as glutamate transporter GLT1. Although pathways regulating the early fate specification of astroglia have been characterized, mechanisms regulating postnatal maturation of astroglia remain essentially unknown. Here we used a new in vivo approach to illustrate and quantitatively analyze developmental arborization of astroglial processes. Our analysis found a particularly high increase in the number of VGluT1(+) neuronal glutamatergic synapses that are ensheathed by processes from individual developing astroglia from postnatal day (P) 14 to P26, when astroglia undergo dramatic postnatal maturation. Subsequent silencing of VGluT1(+) synaptic activity in VGluT1 KO mice significantly reduces astroglial domain growth and the induction of GLT1 in the cortex, but has no effect on astroglia in the hypothalamus, where non-VGluT1(+) synaptic signaling predominates. In particular, electron microscopy analysis showed that the loss of VGluT1(+) synaptic signaling significantly decreases perisynaptic enshealthing of astroglial processes on synapses. To further determine whether synaptically released glutamate mediates VGluT1(+) synaptic signaling, we pharmacologically inhibited and genetically ablated metabotropic glutamate receptors (mGluRs, especially mGluR5) in developing cortical astroglia and found that developmental arborization of astroglial processes and expression of functional proteins, such as GLT1, is significantly decreased. In summary, our genetic analysis provides new in vivo evidence that VGluT1(+) glutamatergic signaling, mediated by the astroglial mGluR5 receptor, regulates the functional maturation of cortical astroglia during development. These results elucidate a new mechanism for regulating the developmental formation of functional neuron-glia synaptic units. PMID- 25122896 TI - A single-system model predicts recognition memory and repetition priming in amnesia. AB - We challenge the claim that there are distinct neural systems for explicit and implicit memory by demonstrating that a formal single-system model predicts the pattern of recognition memory (explicit) and repetition priming (implicit) in amnesia. In the current investigation, human participants with amnesia categorized pictures of objects at study and then, at test, identified fragmented versions of studied (old) and nonstudied (new) objects (providing a measure of priming), and made a recognition memory judgment (old vs new) for each object. Numerous results in the amnesic patients were predicted in advance by the single system model, as follows: (1) deficits in recognition memory and priming were evident relative to a control group; (2) items judged as old were identified at greater levels of fragmentation than items judged new, regardless of whether the items were actually old or new; and (3) the magnitude of the priming effect (the identification advantage for old vs new items) overall was greater than that of items judged new. Model evidence measures also favored the single-system model over two formal multiple-systems models. The findings support the single-system model, which explains the pattern of recognition and priming in amnesia primarily as a reduction in the strength of a single dimension of memory strength, rather than a selective explicit memory system deficit. PMID- 25122897 TI - Neurovascular coupling and decoupling in the cortex during voluntary locomotion. AB - Hemodynamic signals are widely used to infer neural activity in the brain. We tested the hypothesis that hemodynamic signals faithfully report neural activity during voluntary behaviors by measuring cerebral blood volume (CBV) and neural activity in the somatosensory cortex and frontal cortex of head-fixed mice during locomotion. Locomotion induced a large and robust increase in firing rate and gamma-band (40-100 Hz) power in the local field potential in the limb representations in somatosensory cortex, and was accompanied by increases in CBV, demonstrating that hemodynamic signals are coupled with neural activity in this region. However, in the frontal cortex, CBV did not change during locomotion, but firing rate and gamma-band power both increased, indicating a decoupling of neural activity from the hemodynamic signal. These results show that hemodynamic signals are not faithful indicators of the mean neural activity in the frontal cortex during locomotion; thus, the results from fMRI and other hemodynamic imaging methodologies for studying neural processes must be interpreted with caution. PMID- 25122898 TI - Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning. AB - An essential aspect of episodic memory is the formation of associations between neutral sensory cues in the environment. In light of recent evidence that this critical aspect of learning does not require the hippocampus, we tested the involvement of the retrosplenial cortex (RSC) in this process using a chemogenetic approach that allowed us to temporarily silence neurons along the entire rostrocaudal extent of the RSC. A viral vector containing the gene for a synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC. When the receptor was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transiently silenced (confirmed using a patch-clamp procedure). Rats expressing hM4Di and control rats were trained in a sensory preconditioning procedure in which a tone and light were paired on some trials and a white noise stimulus was presented alone on the other trials during the Preconditioning phase. Thus, rats were given the opportunity to form an association between a tone and a light in the absence of reinforcement. Later, the light was paired with food. During the test phase when the auditory cues were presented alone, controls exhibited more conditioned responding during presentation of the tone compared with the white noise reflecting the prior formation of a tone-light association. Silencing RSC neurons during the Preconditioning phase prevented the formation of an association between the tone and light and eliminated the sensory preconditioning effect. These findings indicate that RSC may contribute to episodic memory formation by linking essential sensory stimuli during learning. PMID- 25122900 TI - Differential contribution of hippocampal subfields to components of associative taste learning. AB - The ability to associate the consumption of a taste with its positive or negative consequences is fundamental to survival and influences the behavior of species ranging from invertebrate to human. As a result, for both research and clinical reasons, there has been a great effort to understand the neuronal circuits, as well as the cellular and molecular mechanisms, underlying taste learning. From a neuroanatomical perspective, the contributions of the cortex and amygdala are well documented; however, the literature is riddled with conflicting results regarding the role of the hippocampus in different facets of taste learning. Here, we use conditional genetics in mice to block NMDA receptor-dependent plasticity individually in each of the three major hippocampal subfields, CA1, CA3, and the dentate gyrus, via deletion of the NR1 subunit. Across the CA1, CA3, and dentate gyrus NR1 knock-out lines, we uncover a pattern of differential deficits that establish the dispensability of hippocampal plasticity in incidental taste learning, the requirement of CA1 plasticity for associative taste learning, and a specific requirement for plasticity in the dentate gyrus when there is a long temporal gap between the taste and its outcome. Together, these data establish that the hippocampus is involved in associative taste learning and suggest an episodic component to this type of memory. PMID- 25122899 TI - Spinal cord injury causes brain inflammation associated with cognitive and affective changes: role of cell cycle pathways. AB - Experimental spinal cord injury (SCI) causes chronic neuropathic pain associated with inflammatory changes in thalamic pain regulatory sites. Our recent studies examining chronic pain mechanisms after rodent SCI showed chronic inflammatory changes not only in thalamus, but also in other regions including hippocampus and cerebral cortex. Because changes appeared similar to those in our rodent TBI models that are associated with neurodegeneration and neurobehavioral dysfunction, we examined effects of mouse SCI on cognition, depressive-like behavior, and brain inflammation. SCI caused spatial and retention memory impairment and depressive-like behavior, as evidenced by poor performance in the Morris water maze, Y-maze, novel objective recognition, step-down passive avoidance, tail suspension, and sucrose preference tests. SCI caused chronic microglial activation in the hippocampus and cerebral cortex, where microglia with hypertrophic morphologies and M1 phenotype predominated. Stereological analyses showed significant neuronal loss in the hippocampus at 12 weeks but not 8 d after injury. Increased cell-cycle-related gene (cyclins A1, A2, D1, E2F1, and PCNA) and protein (cyclin D1 and CDK4) expression were found chronically in hippocampus and cerebral cortex. Systemic administration of the selective cyclin dependent kinase inhibitor CR8 after SCI significantly reduced cell cycle gene and protein expression, microglial activation and neurodegeneration in the brain, cognitive decline, and depression. These studies indicate that SCI can initiate a chronic brain neurodegenerative response, likely related to delayed, sustained induction of M1-type microglia and related cell cycle activation, which result in cognitive deficits and physiological depression. PMID- 25122902 TI - Interplay between synchronization of multivesicular release and recruitment of additional release sites support short-term facilitation at hippocampal mossy fiber to CA3 pyramidal cells synapses. AB - Synaptic short-term plasticity is a key regulator of neuronal communication and is controlled via various mechanisms. A well established property of mossy fiber to CA3 pyramidal cell synapses is the extensive short-term facilitation during high-frequency bursts. We investigated the mechanisms governing facilitation using a combination of whole-cell electrophysiological recordings, electrical minimal stimulation, and random-access two-photon microscopy in acute mouse hippocampal slices. Two distinct presynaptic mechanisms were involved in short term facilitation, with their relative contribution dependent on extracellular calcium concentration. The synchronization of multivesicular release was observed during trains of facilitating EPSCs recorded in 1.2 mM external Ca(2+) ([Ca(2+)]e). Indeed, covariance analysis revealed a gradual augmentation in quantal size during trains of EPSCs, and application of the low-affinity glutamate receptor antagonist gamma-D-glutamylglycine showed an increase in cleft glutamate concentration during paired-pulse stimulation. Whereas synchronization of multivesicular release contributed to the facilitation in 1.2 mM [Ca(2+)]e, variance-mean analysis showed that recruitment of more release sites (N) was likely to account for the larger facilitation observed in 2.5 mM [Ca(2+)]e. Furthermore, this increase in N could be promoted by calcium microdomains of heterogeneous amplitudes observed in single mossy fiber boutons. Our findings suggest that the combination of multivesicular release and the recruitment of additional release sites act together to increase glutamate release during burst activity. This is supported by the compartmentalized spatial profile of calcium elevations in boutons and helps to expand the dynamic range of mossy fibers information transfer. PMID- 25122901 TI - The essential role of primate orbitofrontal cortex in conflict-induced executive control adjustment. AB - Conflict in information processing evokes trial-by-trial behavioral modulations. Influential models suggest that adaptive tuning of executive control, mediated by mid-dorsal lateral prefrontal cortex (mdlPFC) and anterior cingulate cortex (ACC), underlies these modulations. However, mdlPFC and ACC are parts of distributed brain networks including orbitofrontal cortex (OFC), posterior cingulate cortex (PCC), and superior-dorsal lateral prefrontal cortex (sdlPFC). Contributions of these latter areas in adaptive tuning of executive control are unknown. We trained monkeys to perform a matching task in which they had to resolve the conflict between two behavior-guiding rules. Here, we report that bilateral lesions in OFC, but not in PCC or sdlPFC, impaired selection between these competing rules. In addition, the behavioral adaptation that is normally induced by experiencing conflict disappeared in OFC-lesioned, but remained normal in PCC-lesioned or sdlPFC-lesioned monkeys. Exploring underlying neuronal processes, we found that the activity of neurons in OFC represented the conflict between behavioral options independent from the other aspects of the task. Responses of OFC neurons to rewards also conveyed information of the conflict level that the monkey had experienced along the course to obtain the reward. Our findings indicate dissociable functions for five closely interconnected cortical areas suggesting that OFC and mdlPFC, but not PCC or sdlPFC or ACC, play indispensable roles in conflict-dependent executive control of on-going behavior. Both mdlPFC and OFC support detection of conflict and its integration with the task goal, but in contrast to mdlPFC, OFC does not retain the necessary information for conflict-induced modulation of future decisions. PMID- 25122904 TI - Dynamic target match signals in perirhinal cortex can be explained by instantaneous computations that act on dynamic input from inferotemporal cortex. AB - Finding sought objects requires the brain to combine visual and target signals to determine when a target is in view. To investigate how the brain implements these computations, we recorded neural responses in inferotemporal cortex (IT) and perirhinal cortex (PRH) as macaque monkeys performed a delayed-match-to-sample target search task. Our data suggest that visual and target signals were combined within or before IT in the ventral visual pathway and then passed onto PRH, where they were reformatted into a more explicit target match signal over ~10-15 ms. Accounting for these dynamics in PRH did not require proposing dynamic computations within PRH itself but, rather, could be attributed to instantaneous PRH computations performed upon an input representation from IT that changed with time. We found that the dynamics of the IT representation arose from two commonly observed features: individual IT neurons whose response preferences were not simply rescaled with time and variable response latencies across the population. Our results demonstrate that these types of time-varying responses have important consequences for downstream computation and suggest that dynamic representations can arise within a feedforward framework as a consequence of instantaneous computations performed upon time-varying inputs. PMID- 25122906 TI - Post-error slowing as a consequence of disturbed low-frequency oscillatory phase entrainment. AB - A common finding across many reaction time tasks is that people slow down on trials following errors, a phenomenon known as post-error slowing. In the present study, we tested a novel hypothesis about the neural mechanism underlying post error slowing. Recent research has shown that when task-relevant stimuli occur in a rhythmic stream, neuronal oscillations entrain to the task structure, thereby enhancing reaction speed. We hypothesized that under such circumstances post error slowing results from an error-induced disturbance of this endogenous brain rhythm. To test this hypothesis, we measured oscillatory EEG dynamics while human subjects performed a demanding discrimination task under time pressure. We found that low-frequency neuronal oscillations entrained to the stimulus presentation rhythm, and that the low-frequency phase at stimulus onset predicted the speed of responding. Importantly, we found that this entrainment was disrupted following errors, and that the degree of phase disturbance was closely related to the degree of post-error slowing on the subsequent trial. These results describe a new mechanism underlying behavioral changes following errors. PMID- 25122907 TI - Recycling endosomes undergo rapid closure of a fusion pore on exocytosis in neuronal dendrites. AB - Exocytosis of recycling endosomes (REs) represents the last step of receptor and membrane recycling, a fundamental process involved in many aspects of cell physiology. In neurons, it is involved in the control of cell polarity and synaptic plasticity and is locally and tightly regulated. However, its molecular mechanisms are still poorly understood. We have imaged single exocytosis events of REs in rat hippocampal neurons in culture transfected with three types of receptors tagged with the pH-sensitive GFP mutant superecliptic phluorin. We found that exocytosis events are grouped into two categories: (1) short burst events in which receptors diffuse into the plasma membrane in a few seconds; and (2) long display events in which receptors remain visible and clustered after exocytosis for many seconds. Display events are much rarer in non-neuronal cells, such as fibroblasts and astrocytes. Using two-color imaging and fast extracellular solution changes, we show that display events correspond to the rapid opening and closing of a fusion pore (or "kiss-and-run") with a median opening time of 2.6 s, which restricts the diffusion of multiple receptor types and bound cargo. Moreover, the RE marker Rab11 remains enriched after display exocytosis events and controls the mode of RE exocytosis. Finally, a given RE can undergo multiple rounds of display exocytosis. The last step of recycling can thus be controlled in neurons for the selective delivery of receptors at the cell surface. PMID- 25122903 TI - A heroin addiction severity-associated intronic single nucleotide polymorphism modulates alternative pre-mRNA splicing of the MU opioid receptor gene OPRM1 via hnRNPH interactions. AB - Single nucleotide polymorphisms (SNPs) in the OPRM1 gene have been associated with vulnerability to opioid dependence. The current study identifies an association of an intronic SNP (rs9479757) with the severity of heroin addiction among Han-Chinese male heroin addicts. Individual SNP analysis and haplotype based analysis with additional SNPs in the OPRM1 locus showed that mild heroin addiction was associated with the AG genotype, whereas severe heroin addiction was associated with the GG genotype. In vitro studies such as electrophoretic mobility shift assay, minigene, siRNA, and antisense morpholino oligonucleotide studies have identified heterogeneous nuclear ribonucleoprotein H (hnRNPH) as the major binding partner for the G-containing SNP site. The G-to-A transition weakens hnRNPH binding and facilitates exon 2 skipping, leading to altered expressions of OPRM1 splice-variant mRNAs and hMOR-1 proteins. Similar changes in splicing and hMOR-1 proteins were observed in human postmortem prefrontal cortex with the AG genotype of this SNP when compared with the GG genotype. Interestingly, the altered splicing led to an increase in hMOR-1 protein levels despite decreased hMOR-1 mRNA levels, which is likely contributed by a concurrent increase in single transmembrane domain variants that have a chaperone-like function on MOR-1 protein stability. Our studies delineate the role of this SNP as a modifier of OPRM1 alternative splicing via hnRNPH interactions, and suggest a functional link between an SNP-containing splicing modifier and the severity of heroin addiction. PMID- 25122905 TI - Characterization of transcriptomes of cochlear inner and outer hair cells. AB - Inner hair cells (IHCs) and outer hair cells (OHCs) are the two types of sensory receptor cells that are critical for hearing in the mammalian cochlea. IHCs and OHCs have different morphology and function. The genetic mechanisms that define their morphological and functional specializations are essentially unknown. The transcriptome reflects the genes that are being actively expressed in a cell and holds the key to understanding the molecular mechanisms of the biological properties of the cell. Using DNA microarray, we examined the transcriptome of 2000 individually collected IHCs and OHCs from adult mouse cochleae. We show that 16,647 and 17,711 transcripts are expressed in IHCs and OHCs, respectively. Of those genes, ~73% are known genes, 22% are uncharacterized sequences, and 5.0% are noncoding RNAs in both populations. A total of 16,117 transcripts are expressed in both populations. Uniquely and differentially expressed genes account for <15% of all genes in either cell type. The top 10 differentially expressed genes include Slc17a8, Dnajc5b, Slc1a3, Atp2a3, Osbpl6, Slc7a14, Bcl2, Bin1, Prkd1, and Map4k4 in IHCs and Slc26a5, C1ql1, Strc, Dnm3, Plbd1, Lbh, Olfm1, Plce1, Tectb, and Ankrd22 in OHCs. We analyzed commonly and differentially expressed genes with the focus on genes related to hair cell specializations in the apical, basolateral, and synaptic membranes. Eighty-three percent of the known deafness-related genes are expressed in hair cells. We also analyzed genes involved in cell-cycle regulation. Our dataset holds an extraordinary trove of information about the molecular mechanisms underlying hair cell morphology, function, pathology, and cell-cycle control. PMID- 25122909 TI - Volitional walking via upper limb muscle-controlled stimulation of the lumbar locomotor center in man. AB - Gait disturbance in individuals with spinal cord lesion is attributed to the interruption of descending pathways to the spinal locomotor center, whereas neural circuits below and above the lesion maintain their functional capability. An artificial neural connection (ANC), which bridges supraspinal centers and locomotor networks in the lumbar spinal cord beyond the lesion site, may restore the functional impairment. To achieve an ANC that sends descending voluntary commands to the lumbar locomotor center and bypasses the thoracic spinal cord, upper limb muscle activity was converted to magnetic stimuli delivered noninvasively over the lumbar vertebra. Healthy participants were able to initiate and terminate walking-like behavior and to control the step cycle through an ANC controlled by volitional upper limb muscle activity. The walking like behavior stopped just after the ANC was disconnected from the participants even when the participant continued to swing arms. Furthermore, additional simultaneous peripheral electrical stimulation to the foot via the ANC enhanced this walking-like behavior. Kinematics of the induced behaviors were identical to those observed in voluntary walking. These results demonstrate that the ANC induces volitionally controlled, walking-like behavior of the legs. This paradigm may be able to compensate for the dysfunction of descending pathways by sending commands to the preserved locomotor center at the lumbar spinal cord and may enable individuals with paraplegia to regain volitionally controlled walking. PMID- 25122910 TI - Perceptual gloss parameters are encoded by population responses in the monkey inferior temporal cortex. AB - There are neurons localized in the lower bank of the superior temporal sulcus (STS) in the inferior temporal (IT) cortex of the monkey that selectively respond to specific ranges of gloss characterized by combinations of three physical reflectance parameters: specular reflectance (rhos), diffuse reflectance (rhod), and spread of specular reflection (alpha; Nishio et al., 2012). In the present study, we examined how the activities of these gloss-selective IT neurons are related to perceived gloss. In an earlier psychophysical study, Ferwerda et al. (2001) identified a perceptually uniform gloss space defined by two axes where the c-axis corresponds to a nonlinear combination of rhos and rhod and the d-axis corresponds to 1 - alpha. In the present study, we tested the responses of gloss selective neurons to stimuli in the perceptual gloss space defined by the c- and d-axes. We found that gloss-selective neurons systematically changed their responses in the perceptual gloss space, and the distribution of the tuning directions of the population of gloss-selective neurons is biased toward directions in which perceived gloss increases. We also found that a set of perceptual gloss parameters as well as surface albedo can be well explained by the population activities of gloss-selective neurons, and that these parameters are likely encoded by the gloss-selective neurons in this area of the STS to represent various glosses. These results thus provide evidence that the IT cortex represents perceptual gloss space. PMID- 25122908 TI - Multisensory training improves auditory spatial processing following bilateral cochlear implantation. AB - Cochlear implants (CIs) partially restore hearing to the deaf by directly stimulating the inner ear. In individuals fitted with CIs, lack of auditory experience due to loss of hearing before language acquisition can adversely impact outcomes. For example, adults with early-onset hearing loss generally do not integrate inputs from both ears effectively when fitted with bilateral CIs (BiCIs). Here, we used an animal model to investigate the effects of long-term deafness on auditory localization with BiCIs and approaches for promoting the use of binaural spatial cues. Ferrets were deafened either at the age of hearing onset or as adults. All animals were implanted in adulthood, either unilaterally or bilaterally, and were subsequently assessed for their ability to localize sound in the horizontal plane. The unilaterally implanted animals were unable to perform this task, regardless of the duration of deafness. Among animals with BiCIs, early-onset hearing loss was associated with poor auditory localization performance, compared with late-onset hearing loss. However, performance in the early-deafened group with BiCIs improved significantly after multisensory training with interleaved auditory and visual stimuli. We demonstrate a possible neural substrate for this by showing a training-induced improvement in the responsiveness of auditory cortical neurons and in their sensitivity to interaural level differences, the principal localization cue available to BiCI users. Importantly, our behavioral and physiological evidence demonstrates a facilitative role for vision in restoring auditory spatial processing following potential cross-modal reorganization. These findings support investigation of a similar training paradigm in human CI users. PMID- 25122911 TI - Microsaccadic responses indicate fast categorization of sounds: a novel approach to study auditory cognition. AB - The mental chronometry of the human brain's processing of sounds to be categorized as targets has intensively been studied in cognitive neuroscience. According to current theories, a series of successive stages consisting of the registration, identification, and categorization of the sound has to be completed before participants are able to report the sound as a target by button press after ~300-500 ms. Here we use miniature eye movements as a tool to study the categorization of a sound as a target or nontarget, indicating that an initial categorization is present already after 80-100 ms. During visual fixation, the rate of microsaccades, the fastest components of miniature eye movements, is transiently modulated after auditory stimulation. In two experiments, we measured microsaccade rates in human participants in an auditory three-tone oddball paradigm (including rare nontarget sounds) and observed a difference in the microsaccade rates between targets and nontargets as early as 142 ms after sound onset. This finding was replicated in a third experiment with directed saccades measured in a paradigm in which tones had to be matched to score-like visual symbols. Considering the delays introduced by (motor) signal transmission and data analysis constraints, the brain must have differentiated target from nontarget sounds as fast as 80-100 ms after sound onset in both paradigms. We suggest that predictive information processing for expected input makes higher cognitive attributes, such as a sound's identity and category, available already during early sensory processing. The measurement of eye movements is thus a promising approach to investigate hearing. PMID- 25122912 TI - Amyloid precursor protein dimerization and synaptogenic function depend on copper binding to the growth factor-like domain. AB - Accumulating evidence suggests that the copper-binding amyloid precursor protein (APP) has an essential synaptic function. APP synaptogenic function depends on trans-directed dimerization of the extracellular E1 domain encompassing a growth factor-like domain (GFLD) and a copper-binding domain (CuBD). Here we report the 1.75 A crystal structure of the GFLD in complex with a copper ion bound with high affinity to an extended hairpin loop at the dimerization interface. In coimmunoprecipitation assays copper binding promotes APP interaction, whereas mutations in the copper-binding sites of either the GFLD or CuBD result in a drastic reduction in APP cis-orientated dimerization. We show that copper is essential and sufficient to induce trans-directed dimerization of purified APP. Furthermore, a mixed culture assay of primary neurons with HEK293 cells expressing different APP mutants revealed that APP potently promotes synaptogenesis depending on copper binding to the GFLD. Together, these findings demonstrate that copper binding to the GFLD of APP is required for APP cis-/trans directed dimerization and APP synaptogenic function. Thus, neuronal activity or disease-associated changes in copper homeostasis likely go along with altered APP synaptic function. PMID- 25122913 TI - Escaping compound eye ancestry: the evolution of single-chamber eyes in holometabolous larvae. AB - Stemmata, the eyes of holometabolous insect larvae, have gained little attention, even though they exhibit remarkably different optical solutions, ranging from compound eyes with upright images, to sophisticated single-chamber eyes with inverted images. Such optical differences raise the question of how major transitions may have occurred. Stemmata evolved from compound eye ancestry, and optical differences are apparent even in some of the simplest systems that share strong cellular homology with adult ommatidia. The transition to sophisticated single-chamber eyes occurred many times independently, and in at least two different ways: through the fusion of many ommatidia [as in the sawfly (Hymenoptera)], and through the expansion of single ommatidia [as in tiger beetles (Coleoptera), antlions (Neuroptera) and dobsonflies (Megaloptera)]. Although ommatidia-like units frequently have multiple photoreceptor layers (tiers), sophisticated image-forming stemmata tend to only have one photoreceptor tier, presumably a consequence of the lens only being able to efficiently focus light on to one photoreceptor layer. An interesting exception is found in some diving beetles [Dytiscidae (Coleoptera)], in which two retinas receive sharp images from a bifocal lens. Taken together, stemmata represent a great model system to study an impressive set of optical solutions that evolved from a relatively simple ancestral organization. PMID- 25122914 TI - The role of titin in eccentric muscle contraction. AB - Muscle contraction and force regulation in skeletal muscle have been thought to occur exclusively through the relative sliding of and the interaction between the contractile filaments actin and myosin. While this two-filament sarcomere model has worked well in explaining the properties of isometrically and concentrically contracting muscle, it has failed miserably in explaining experimental observations in eccentric contractions. Here, I suggest, and provide evidence, that a third filament, titin, is involved in force regulation of sarcomeres by adjusting its stiffness in an activation-dependent (calcium) and active force dependent manner. Upon muscle activation, titin binds calcium at specific sites, thereby increasing its stiffness, and cross-bridge attachment to actin is thought to free up binding sites for titin on actin, thereby reducing titin's free-spring length, thus increasing its stiffness and force upon stretch of active muscle. This role of titin as a third force regulating myofilament in sarcomeres, although not fully proven, would account for many of the unexplained properties of eccentric muscle contraction, while simultaneously not affecting the properties predicted by the two-filament cross-bridge model in isometric and concentric muscle function. Here, I identify the problems of the two-filament sarcomere model and demonstrate the advantages of the three-filament model by providing evidence of titin's contribution to active force in eccentric muscle function. PMID- 25122916 TI - Feeding rates and under-ice foraging strategies of the smallest lunge filter feeder, the Antarctic minke whale (Balaenoptera bonaerensis). AB - Body size and feeding mode are two fundamental characteristics that determine foraging performance and ecological niche. As the smallest obligate lunge filter feeders, minke whales represent an ideal system for studying the physical and energetic limits of filter feeding in endotherms. We used multi-sensor suction cup tags to quantify the feeding performance of Antarctic minke whales. Foraging dives around and beneath sea ice contained up to 24 lunges per dive, the highest feeding rates for any lunge-feeding whale. Their small size allows minke whales access to krill in sea-ice environments not easily accessible to larger baleen whales. Furthermore, their ability to filter feed provides an advantage over other smaller sympatric krill predators such as penguins and seals that feed on individual prey. The unique combination of body size, feeding mechanism and sea ice habitat of Antarctic minke whales defines a previously undocumented energetic niche that is unique among aquatic vertebrates. PMID- 25122915 TI - Temporal binding of neural responses for focused attention in biosonar. AB - Big brown bats emit biosonar sounds and perceive their surroundings from the delays of echoes received by the ears. Broadcasts are frequency modulated (FM) and contain two prominent harmonics sweeping from 50 to 25 kHz (FM1) and from 100 to 50 kHz (FM2). Individual frequencies in each broadcast and each echo evoke single-spike auditory responses. Echo delay is encoded by the time elapsed between volleys of responses to broadcasts and volleys of responses to echoes. If echoes have the same spectrum as broadcasts, the volley of neural responses to FM1 and FM2 is internally synchronized for each sound, which leads to sharply focused delay images. Because of amplitude-latency trading, disruption of response synchrony within the volleys occurs if the echoes are lowpass filtered, leading to blurred, defocused delay images. This effect is consistent with the temporal binding hypothesis for perceptual image formation. Bats perform inexplicably well in cluttered surroundings where echoes from off-side objects ought to cause masking. Off-side echoes are lowpass filtered because of the shape of the broadcast beam, and they evoke desynchronized auditory responses. The resulting defocused images of clutter do not mask perception of focused images for targets. Neural response synchronization may select a target to be the focus of attention, while desynchronization may impose inattention on the surroundings by defocusing perception of clutter. The formation of focused biosonar images from synchronized neural responses, and the defocusing that occurs with disruption of synchrony, quantitatively demonstrates how temporal binding may control attention and bring a perceptual object into existence. PMID- 25122917 TI - Pre-start timing information is used to set final linear speed in a C-start manoeuvre. AB - In their unique hunting behaviour, archerfish use a complex motor decision to secure their prey: based solely on how dislodged prey initially falls, they select an adapted C-start manoeuvre that turns the fish right towards the point on the water surface where their prey will later land. Furthermore, they take off at a speed that is set so as to arrive in time. We show here that the C-start manoeuvre and not subsequent tail beating is necessary and sufficient for setting this adaptive level of speed. Furthermore, the C-start pattern is adjusted to independently determine both the turning angle and the take-off speed. The selection of both aspects requires no a priori information and is done based on information sampled from the onset of target motion until the C-start is launched. Fin strokes can occur right after the C-start manoeuvre but are not required to fine-tune take-off speed, but rather to maintain it. By probing the way in which the fish set their take-off speed in a wide range of conditions in which distance from the later catching point and time until impact varied widely and unpredictably, we found that the C-start manoeuvre is programmed based on pre C-start estimates of distance and time until impact. Our study hence provides the first evidence for a C-start that is fine-tuned to produce an adaptive speed level. PMID- 25122918 TI - Adaptive changes in echolocation sounds by Pipistrellus abramus in response to artificial jamming sounds. AB - The echolocation behavior of Pipistrellus abramus during exposure to artificial jamming sounds during flight was investigated. Echolocation pulses emitted by the bats were recorded using a telemetry microphone mounted on the bats' backs, and their adaptation based on acoustic characteristics of emitted pulses was assessed in terms of jamming-avoidance responses (JARs). In experiment 1, frequency modulated jamming sounds (3 ms duration) mimicking echolocation pulses of P. abramus were prepared. All bats showed significant increases in the terminal frequency of the frequency-modulated pulse by an average of 2.1-4.5 kHz when the terminal frequency of the jamming sounds was lower than the bats' own pulses. This frequency shift was not observed using jamming frequencies that overlapped with or were higher than the bats' own pulses. These findings suggest that JARs in P. abramus are sensitive to the terminal frequency of jamming pulses and that the bats' response pattern was dependent on the slight difference in stimulus frequency. In experiment 2, when bats were repeatedly exposed to a band-limited noise of 70 ms duration, the bats in flight more frequently emitted pulses during silent periods between jamming sounds, suggesting that the bats could actively change the timing of pulse emissions, even during flight, to avoid temporal overlap with jamming sounds. Our findings demonstrate that bats could adjust their vocalized frequency and emission timing during flight in response to acoustic jamming stimuli. PMID- 25122919 TI - Forward shift of feeding buzz components of dolphins and belugas during associative learning reveals a likely connection to reward expectation, pleasure and brain dopamine activation. AB - For many years, we heard sounds associated with reward from dolphins and belugas. We named these pulsed sounds victory squeals (VS), as they remind us of a child's squeal of delight. Here we put these sounds in context with natural and learned behavior. Like bats, echolocating cetaceans produce feeding buzzes as they approach and catch prey. Unlike bats, cetaceans continue their feeding buzzes after prey capture and the after portion is what we call the VS. Prior to training (or conditioning), the VS comes after the fish reward; with repeated trials it moves to before the reward. During training, we use a whistle or other sound to signal a correct response by the animal. This sound signal, named a secondary reinforcer (SR), leads to the primary reinforcer, fish. Trainers usually name their whistle or other SR a bridge, as it bridges the time gap between the correct response and reward delivery. During learning, the SR becomes associated with reward and the VS comes after the SR rather than after the fish. By following the SR, the VS confirms that the animal expects a reward. Results of early brain stimulation work suggest to us that SR stimulates brain dopamine release, which leads to the VS. Although there are no direct studies of dopamine release in cetaceans, we found that the timing of our VS is consistent with a response after dopamine release. We compared trained vocal responses to auditory stimuli with VS responses to SR sounds. Auditory stimuli that did not signal reward resulted in faster responses by a mean of 151 ms for dolphins and 250 ms for belugas. In laboratory animals, there is a 100 to 200 ms delay for dopamine release. VS delay in our animals is similar and consistent with vocalization after dopamine release. Our novel observation suggests that the dopamine reward system is active in cetacean brains. PMID- 25122921 TI - Genetic evidence for monogamy in the dwarf seahorse, Hippocampus zosterae. AB - Syngnathid fishes (pipefishes, seahorses, and seadragons) exhibit a wide array of mating systems ranging from monogamy with long-term pair bonds to more promiscuous mating systems, such as polyandry and polygynandry. Some seahorses, including the dwarf seahorse Hippocampus zosterae, have been found to be socially monogamous. Although several seahorse species have also been shown to be genetically monogamous, parentage analysis has not yet been applied to the dwarf seahorse. We developed 8 novel microsatellites for the dwarf seahorse to conduct genetic parentage analysis to confirm that this species is indeed monogamous. Using 4 selected loci and a total of 16 pregnant male seahorses, with 8 collected in Florida and 8 sampled in Texas, we genotyped all of the offspring within each male's brood to determine the maternal contributions to each brood. We found a maximum of 4 alleles per locus segregating within each pregnant male's brood, a pattern consistent with each brood having exactly 1 mother and 1 father. These results support previous laboratory-based behavioral studies and indicate that the dwarf seahorse, H. zosterae, is genetically monogamous. PMID- 25122923 TI - Secretion and immunogenicity of the meningioma-associated antigen TXNDC16. AB - In a previous study, we identified thioredoxin domain containing 16 (TXNDC16) as a meningioma-associated Ag by protein macroarray screening. Serological screening detected autoantibodies against TXNDC16 exclusively in meningioma patients' sera and not in sera of healthy controls. TXNDC16 was previously found to be an endoplasmic reticulum (ER)-luminal glycoprotein. In this study, we show an additional ER-associated localization of TXNDC16 in the cytosol by in vitro synthesis, molecular mass shift assay, and flow cytometry. We were able to show TXNDC16 secretion in different human cell lines due to masked and therefore nonfunctional ER retrieval motif. A previously indicated exosomal TXNDC16 secretion could not be confirmed in HEK293 cells. The secreted serum protein TXNDC16 is bound in circulating immune complexes, which were found both in meningioma and healthy blood donor sera. Employing a customized array with 163 overlapping TXNDC16 peptides and measuring autoantibody reactivity, we achieved discrimination of meningioma sera from healthy controls with an accuracy of 87.2% using a set of only five immunogenic TXNDC16 epitopes. PMID- 25122924 TI - Antibody-mediated immune suppression of erythrocyte alloimmunization can occur independently from red cell clearance or epitope masking in a murine model. AB - Anti-D can prevent immunization to the RhD Ag on RBCs, a phenomenon commonly termed Ab-mediated immune suppression (AMIS). The most accepted theory to explain this effect has been the rapid clearance of RBCs. In mouse models using SRBC, these xenogeneic cells are always rapidly cleared even without Ab, and involvement of epitope masking of the SRBC Ags by the AMIS-inducing Ab (anti SRBC) has been suggested. To address these hypotheses, we immunized mice with murine transgenic RBCs expressing the HOD Ag (hen egg lysozyme [HEL], in sequence with ovalbumin, and the human Duffy transmembrane protein) in the presence of polyclonal Abs or mAbs to the HOD molecule. The isotype, specificity, and ability to induce AMIS of these Abs were compared with accelerated clearance as well as steric hindrance of the HOD Ag. Mice made IgM and IgG reactive with the HEL portion of the molecule only. All six of the mAbs could inhibit the response. The HEL-specific Abs (4B7, IgG1; GD7, IgG2b; 2F4, IgG1) did not accelerate clearance of the HOD-RBCs and displayed partial epitope masking. The Duffy-specific Abs (MIMA 29, IgG2a; CBC-512, IgG1; K6, IgG1) all caused rapid clearance of HOD RBCs without steric hindrance. To our knowledge, this is the first demonstration of AMIS to erythrocytes in an all-murine model and shows that AMIS can occur in the absence of RBC clearance or epitope masking. The AMIS effect was also independent of IgG isotype and epitope specificity of the AMIS-inducing Ab. PMID- 25122922 TI - The natural product phyllanthusmin C enhances IFN-gamma production by human NK cells through upregulation of TLR-mediated NF-kappaB signaling. AB - Natural products are a major source for cancer drug development. NK cells are a critical component of innate immunity with the capacity to destroy cancer cells, cancer-initiating cells, and clear viral infections. However, few reports describe a natural product that stimulates NK cell IFN-gamma production and unravel a mechanism of action. In this study, through screening, we found that a natural product, phyllanthusmin C (PL-C), alone enhanced IFN-gamma production by human NK cells. PL-C also synergized with IL-12, even at the low cytokine concentration of 0.1 ng/ml, and stimulated IFN-gamma production in both human CD56(bright) and CD56(dim) NK cell subsets. Mechanistically, TLR1 and/or TLR6 mediated PL-C's activation of the NF-kappaB p65 subunit that in turn bound to the proximal promoter of IFNG and subsequently resulted in increased IFN-gamma production in NK cells. However, IL-12 and IL-15Rs and their related STAT signaling pathways were not responsible for the enhanced IFN-gamma secretion by PL-C. PL-C induced little or no T cell IFN-gamma production or NK cell cytotoxicity. Collectively, we identify a natural product with the capacity to selectively enhance human NK cell IFN-gamma production. Given the role of IFN gamma in immune surveillance, additional studies to understand the role of this natural product in prevention of cancer or infection in select populations are warranted. PMID- 25122930 TI - Early events in annelid regeneration: a cellular perspective. AB - The ability to regenerate extensive portions of the body is widespread among the phylum Annelida and this group includes some of the most highly regenerative animals known. Knowledge of the cellular and molecular basis of regeneration in this group is thus important for understanding how regenerative processes have evolved both within the group and across animal phyla. Here, the cellular basis of annelid regeneration is reviewed, with a focus on the earliest steps of regeneration, namely wound-healing and formation of the blastema. Information from a wide range of annelids is compiled in order to identify common and variable elements. There is a large body of valuable older literature on the cellular basis of regeneration in annelids and an effort is made to review this literature in addition to more recent studies. Annelids typically seal the wound through muscular contraction and undergo some autolysis of tissue at the site of the wound. Bodily injury elicits extensive cell migration toward the wound, involving several different types of cells. Some migrating cells form a tissue clot and phagocytize damaged tissues, whereas others are inferred to contribute to regenerated tissue, specifically mesodermal tissue. In one annelid subgroup, the clitellates, a group of mesodermal cells, sometimes referred to as neoblasts, is inferred to migrate over considerable distances, with cells moving to the wound from several segments away. Epidermis and gut epithelia severed upon amputation typically heal by fusing with like tissue, although not always. After amputation, cellular contacts with the extracellular matrix are disrupted and major changes in cell morphology and adhesion occur within tissues near the wound. Interactions of tissues at the wound appear key for initiating a blastema, with a particularly important role suggested for the ventral nerve cord, although species are variable in this regard; longer-distance effects mediated by the brain are also reported. The anterior-posterior polarity of the blastema can be mis-assigned, leading most commonly to double-headed worms, and the dorsal ventral polarity of the blastema appears to be induced by the ventral nerve cord. The blastema is thought to arise from contributions of all three tissue layers, with each layer replacing itself in a tissue-specific manner. Blastemal cells originate mostly locally, although some long-distance migration of source-cells is suggested in clitellates. A number of important questions remain about the cellular basis of regeneration in annelids and addressing many of these would be greatly aided by developing approaches to identify and isolate specific cell types and techniques to image and trace cells in vivo. PMID- 25122925 TI - The surprising dynamics of scaffolding proteins. AB - The function of scaffolding proteins is to bring together two or more proteins in a relatively stable configuration, hence their name. Numerous scaffolding proteins are found in nature, many having multiple protein-protein interaction modules. Over the past decade, examples of scaffolding complexes long thought to be stable have instead been found to be surprisingly dynamic. These studies are scattered among different biological systems, and so the concept that scaffolding complexes might not always represent stable entities and that their dynamics can be regulated has not garnered general attention. We became aware of this issue in our studies of a scaffolding protein in microvilli, which forced us to reevaluate its contribution to their structure. The purpose of this Perspective is to draw attention to this phenomenon and discuss why complexes might show regulated dynamics. We also wish to encourage more studies on the dynamics of "stable" complexes and to provide a word of caution about how functionally important dynamic associations may be missed in biochemical and proteomic studies. PMID- 25122933 TI - Don't lose sleep over seasonal affective disorder. PMID- 25122931 TI - Urinary tract infections: what both men and women should know. PMID- 25122928 TI - Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study. AB - More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks' gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks' gestation, the consumption of >=3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70-0.77) and 0.68 (0.63-0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78-1.0] and 0.78 [0.58 0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia. PMID- 25122932 TI - Breaking bones: one fracture can lead to another. PMID- 25122934 TI - I recently developed proctitis after completing radiation treatment for prostate cancer. What should I do? PMID- 25122935 TI - What is an ESR and when is my doctor likely to order it? PMID- 25122936 TI - Your medicine cabinet's best cold fighter. PMID- 25122937 TI - A reason to cry over burnt toast. PMID- 25122939 TI - Master new skills to retain memory. PMID- 25122938 TI - A breakthrough in mantle cell lymphoma. PMID- 25122940 TI - Servicemembers' Group Life Insurance--Veterans' Group Life Insurance regulation update--ABO, VGLI application, SGLI 2-year disability extension. Final rule. AB - This document amends the Department of Veterans Affairs (VA) insurance regulations concerning Servicemembers' Group Life Insurance (SGLI) to reflect the statutory provisions of the Veterans' Benefits Act of 2010, which became law on October 13, 2010, and resulted in the need for amendments to change the SGLI Disability Extension period from 1 year to 2 years in duration; provide SGLI Traumatic Injury Protection (TSGLI) retroactive coverage effective from October 7, 2001, for all qualifying injuries regardless of the geographic location and military operation in which the injuries were incurred; and remove the SGLI and Veterans' Group Life Insurance (VGLI) Accelerated Benefits Option (ABO) discount rate. This rule also clarifies that ''initial premium'' refers to ''initial Veterans' Group Life Insurance premium,'' updates the current address of the Office of Servicemembers' Group Life Insurance (OSGLI), managed by Prudential Insurance Company of America, to reflect where the ABO application is mailed for processing, and corrects the OSGLI phone number. Finally, this rule removes the ABO application form from the regulation, and it corrects and clarifies language concerning the VGLI application period that was inadvertently incorrectly modified in a prior amendment of the regulations. PMID- 25122941 TI - Medicare, Medicaid, and Children's Health Insurance Programs: announcement of the extended temporary moratoria on enrollment of ambulance suppliers and home health agencies in designated geographic locations. Extension of temporary moratoria. AB - This document announces the extension of temporary moratoria on the enrollment of new ambulance suppliers and home health agencies (HHAs) in specific locations within designated metropolitan areas in Florida, Illinois, Michigan, Texas, Pennsylvania, and New Jersey to prevent and combat fraud, waste, and abuse. PMID- 25122942 TI - Schedule for rating disabilities--mental disorders and definition of psychosis for certain VA purposes. Interim final rule. AB - The Department of Veterans Affairs (VA) is amending the portion of its Schedule for Rating Disabilities (VASRD) dealing with mental disorders and its adjudication regulations that define the term ''psychosis.'' The VASRD refers to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV), and VA's adjudication regulations refer to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR). DSM-IV and DSM-IV-TR were recently updated by issuance of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). This rulemaking will remove outdated DSM references by deleting references to DSM-IV and DSM-IV-TR and replacing them with references to DSM-5. Additionally, this rulemaking will update the nomenclature used to refer to certain mental disorders to conform to DSM-5. PMID- 25122944 TI - Administrative simplification: change to the compliance date for the International Classification of Diseases, 10th Revision (ICD-10-CM and ICD-10 PCS) medical data code sets. Final rule. AB - This final rule implements section 212 of the Protecting Access to Medicare Act of 2014 by changing the compliance date for the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) for diagnosis coding, including the Official ICD-10-CM Guidelines for Coding and Reporting, and the International Classification of Diseases, 10th Revision, Procedure Coding System (ICD-10-PCS) for inpatient hospital procedure coding, including the Official ICD 10-PCS Guidelines for Coding and Reporting, from October 1, 2014 to October 1, 2015. It also requires the continued use of the International Classification of Diseases, 9th Revision, Clinical Modification, Volumes 1 and 2 (diagnoses), and 3 (procedures) (ICD-9-CM), including the Official ICD-9-CM Guidelines for Coding and Reporting, through September 30, 2015. PMID- 25122943 TI - Specifications for medical examinations of coal miners. Interim final rule. AB - With this action, the Department of Health and Human Services (HHS), in accordance with a final rule recently published by the Department of Labor's Mine Safety and Health Administration (MSHA), is amending its regulations to establish standards for the approval of facilities that conduct spirometry examinations and to require that all coal mine operators submit a plan for the provision of spirometry and X-ray examinations to all surface and underground coal miners. PMID- 25122945 TI - Final priority; Technical Assistance on State Data Collection--IDEA Data Management Center. Final priority. AB - The Assistant Secretary for the Office of Special Education and Rehabilitative Services (OSERS) announces a priority under the Technical Assistance on State Data Collection program. The Assistant Secretary may use this priority for competitions in fiscal year (FY) 2014 and later years. We take this action to fund a cooperative agreement to establish and operate an IDEA Data Management Center (Center) that will provide technical assistance (TA) to improve the capacity of States to meet the data collection requirements of the Individuals with Disabilities Education Act (IDEA). PMID- 25122946 TI - Medicare program; prospective payment system and consolidated billing for skilled nursing facilities for FY 2015. Final rule. AB - This final rule updates the payment rates used under the prospective payment system (PPS) for skilled nursing facilities (SNFs) for fiscal year (FY) 2015. In addition, it adopts the most recent Office of Management and Budget (OMB) statistical area delineations to identify a facility's urban or rural status for the purpose of determining which set of rate tables will apply to the facility, and to determine the SNF PPS wage index including a 1-year transition with a blended wage index for all providers for FY 2015. This final rule also contains a revision to policies related to the Change of Therapy (COT) Other Medicare Required Assessment (OMRA). This final rule includes a discussion of a provision related to the Affordable Care Act involving Civil Money Penalties. Finally, this final rule discusses the SNF therapy payment research currently underway within CMS, observed trends related to therapy utilization among SNF providers, and the agency's commitment to accelerating health information exchange in SNFs. PMID- 25122947 TI - Medicare program; inpatient rehabilitation facility prospective payment system for federal fiscal year 2015. AB - This final rule updates the prospective payment rates for inpatient rehabilitation facilities (IRFs) for federal fiscal year (FY) 2015 as required by the statute. This final rule finalizes a policy to collect data on the amount and mode (that is, Individual, Concurrent, Group, and Co-Treatment) of therapy provided in the IRF setting according to therapy discipline, revises the list of diagnosis and impairment group codes that presumptively meet the "60 percent rule'' compliance criteria, provides a way for IRFs to indicate on the Inpatient Rehabilitation Facility-Patient Assessment Instrument (IRF-PAI) form whether the prior treatment and severity requirements have been met for arthritis cases to presumptively meet the "60 percent rule'' compliance criteria, and revises and updates quality measures and reporting requirements under the IRF quality reporting program (QRP). This rule also delays the effective date for the revisions to the list of diagnosis codes that are used to determine presumptive compliance under the "60 percent rule'' that were finalized in FY 2014 IRF PPS final rule and adopts the revisions to the list of diagnosis codes that are used to determine presumptive compliance under the "60 percent rule'' that are finalized in this rule. This final rule also addresses the implementation of the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), for the IRF prospective payment system (PPS), which will be effective when ICD-10-CM becomes the required medical data code set for use on Medicare claims and IRF-PAI submissions. PMID- 25122948 TI - Medicare program; inpatient psychiatric facilities prospective payment system- update for fiscal year beginning October 1, 2014 (FY 2015). Final rule. AB - This final rule will update the prospective payment rates for Medicare inpatient hospital services provided by inpatient psychiatric facilities (IPFs). These changes will be applicable to IPF discharges occurring during the fiscal year (FY) beginning October 1, 2014 through September 30, 2015. This final rule will also address implementation of ICD-10-CM and ICD-10-PCS codes; finalize a new methodology for updating the cost of living adjustment (COLA), and finalize new quality measures and reporting requirements under the IPF quality reporting program. PMID- 25122949 TI - Concentrations of mobile source air pollutants in urban microenvironments. AB - Human exposures to criteria and hazardous air pollutants (HAPs) in urban areas vary greatly due to temporal-spatial variations in emissions, changing meteorology, varying proximity to sources, as well as due to building, vehicle, and other environmental characteristics that influence the amounts of ambient pollutants that penetrate or infiltrate into these microenvironments. Consequently, the exposure estimates derived from central-site ambient measurements are uncertain and tend to underestimate actual exposures. The Exposure Classification Project (ECP) was conducted to measure pollutant concentrations for common urban microenvironments (MEs) for use in evaluating the results of regulatory human exposure models. Nearly 500 sets of measurements were made in three Los Angeles County communities during fall 2008, winter 2009, and summer 2009. MEs included in-vehicle, near-road, outdoor and indoor locations accessible to the general public. Contemporaneous 1- to 15-min average personal breathing zone concentrations of carbon monoxide (CO), carbon dioxide (CO2), volatile organic compounds (VOCs), nitric oxide (NO), nitrogen oxides (NO(x)), particulate matter (< 2.5 microm diameter; PM2.5) mass, ultrafine particle (UFP; < 100 nm diameter) number black carbon (BC), speciated HAPs (e.g, benzene, toluene, ethylbenzene, xylenes [BTEX], 1,3-butadiene), and ozone (O3) were measured continuously. In-vehicle and inside/outside measurements were made in various passenger vehicle types and in public buildings to estimate penetration or infiltration factors. A large fraction of the observed pollutant concentrations for on-road MEs, especially near diesel trucks, was unrelated to ambient measurements at nearby monitors. Comparisons of ME concentrations estimated using the median ME/ambient ratio versus regression slopes and intercepts indicate that the regression approach may be more accurate for on-road MEs. Ranges in the ME/ambient ratios among ME categories were generally greater than differences among the three communities for the same ME category, suggesting that the ME proximity factors may be more broadly applicable to urban MEs. Implications: Estimates of population exposure to air pollutants extrapolated from ambient measurements at ambient fixed site monitors or exposure surrogates are prone to uncertainty. This study measured concentrations of mobile source air toxics (MSAT) and related criteria pollutants within in-vehicle, outdoor near road, and indoor urban MEs to provide multipollutant ME measurements that can be used to calibrate regulatory exposure models. PMID- 25122950 TI - Investigation of time-resolved atmospheric conditions and indoor/outdoor particulate matter concentrations in homes with gas and biomass cook stoves in Nogales, Sonora, Mexico. AB - This paper reports findings from a case study designed to investigate indoor and outdoor air quality in homes near the United States-Mexico border During the field study, size-resolved continuous particulate matter (PM) concentrations were measured in six homes, while outdoor PM was simultaneously monitored at the same location in Nogales, Sonora, Mexico, during March 14-30, 2009. The purpose of the experiment was to compare PM in homes using different fuels for cooking, gas versus biomass, and to obtain a spatial distribution of outdoor PM in a region where local sources vary significantly (e.g., highway, border crossing, unpaved roads, industry). Continuous PM data were collected every 6 seconds using a valve switching system to sample indoor and outdoor air at each home location. This paper presents the indoor PM data from each home, including the relationship between indoor and outdoor PM. The meteorological conditions associated with elevated ambient PM events in the region are also discussed. Results indicate that indoor air pollution has a strong dependence on cooking fuel, with gas stoves having hourly averaged median PM3 concentrations in the range of 134 to 157 microg m(-3) and biomass stoves 163 to 504 microg m(-1). Outdoor PM also indicates a large spatial heterogeneity due to the presence of microscale sources and meteorological influences (median PM3: 130 to 770 microg m(-3)). The former is evident in the median and range of daytime PM values (median PM3: 250 microg m(-3), maximum: 9411 microg m(-3)), while the meteorological influences appear to be dominant during nighttime periods (median PM3: 251 microg m(-3), maximum: 10,846 microg m(-3)). The atmospheric stability is quantified for three nighttime temperature inversion episodes, which were associated with an order of magnitude increase in PM10 at the regulatory monitor in Nogales, AZ (maximum increase: 12 to 474 microg m(-3)). Implications: Regulatory air quality standards are based on outdoor ambient air measurements. However, a large fraction of time is typically spent indoors where a variety of activities including cooking, heating, tobacco smoking, and cleaning can lead to elevated PM concentrations. This study investigates the influence of meteorology, outdoor PM, and indoor activities on indoor air pollution (IAP) levels in the United States-Mexico border region. Results indicate that cooking fuel type and meteorology greatly influence the IAP in homes, with biomass fuel use causing the largest increase in PM concentration. PMID- 25122951 TI - Role of sodium ions in the vitrification process: glass matrix modification, slag structure depolymerization, and influence of metal immobilization. AB - This study investigates the role of Na ions, a common flux, in the vitrification process. Artificial glass systems composed of Al2O3, CaO, and SiO2 with various Na concentrations were melted at 1450 degrees C. The specimens were cooled by air cooling and water quenching and the metal mobility was evaluated using a sequential extraction procedure. The X-ray diffraction analysis and scanning electron microscopy observations showed that Na ions governed the air-cooled slag's structure. Na ions initially depolymerized CaSiO3-linked chains into CaSiO3 chains, and further cut them into shorter and nonuniform ones, making the slag structure amorphous. With even more Na ions, CaSiO3 chains were divided into single SiO4 tetrahedrons and formed Na-related crystals (Na2Ca3Si2O8 and NaAlSiO4). The phase distributions of Al, Cr, Cu Mn, and Ni showed that Na has a positive effect on the immobilization of heavy metals at suitable concentrations, but a negative effect when in excess amounts. Implications: Vitrification has been widely used to treat hazardous materials. The Na-bearing additives were often used as a flux to improve the melting process. This study described the role of Na played in the vitrification process. The Na ions acted as glass modifier and depolymerize the chain structure of slag. With adequate addition amount of Na ions, the immobilization of heavy metals was improved. The results provided much information about the crystalline phase variation, metal mobility, and surface characteristics while Na serves as a flux. PMID- 25122952 TI - Particle size distribution and its relationship to black carbon in two urban and one rural site in Santiago de Chile. AB - The size distribution of particles has been studied in three sites in the Metropolitan area of Santiago de Chile in the winter of 2009 and a comparison with black carbon was performed. Two sites are located near busy streets in Santiago and the other site is located in a rural area about 40 km west of Santiago with little influence from vehicles, but large influence from wood burning. The campaign lasted 1 or 2 weeks in each site. We have divided the particle size measurements into four groups (10-39 nm, 40-62 nm, 63-174 nm, and 175-700 nm) in order to compare with the carbon monitor. In the sites near the street, black carbon has a high correlation (R = 0.85) with larger particles (175 700 nm). The correlation decreased when black carbon was compared with smaller particles, having very small correlation with the smallest sizes (10-39 nm). In the rural site, black carbon also has a high correlation (R = 0.86) with larger particles (175-700 nm), but the correlation between black carbon and the finest particles (10-39 nm) decreases to near 0. These measurements are an indication that wood burning does not generate particles smaller than -50 nm. In the urban sites, particle size distribution is peaked toward smaller particles (10-39 nm) only during rush hours, but at other times, particles size distribution is peaked toward larger sizes. When solar radiation was high, evidence of secondary particle formation was seen in the rural site, but not in the urban sites. The correlation between the number of secondary particles and solar radiation was R2 = 0.46, indicating that it there may be other variables that play a role in ultrafine particle formation. Implications: A study of the size distribution of particles and black carbon concentration in two street sites and one rural site shows that in the last site the number of particles ultrafine particles (d < 40 nm) is 10 times lower but the number of larger particles is about 2 times lower. Thus, the rural site has less of the particles that are more dangerous to health. The number ofultrafine particles is mostly associated with traffic, while the number of larger particles is associated with wood burning and other sources. Wood burning does not generate particles smaller than -50 nm. PMID- 25122953 TI - Recovering valuable metals from recycled photovoltaic modules. AB - Recovering valuable metals such as Si, Ag, Cu, and Al has become a pressing issue as end-of-life photovoltaic modules need to be recycled in the near future to meet legislative requirements in most countries. Of major interest is the recovery and recycling of high-purity silicon (> 99.9%) for the production of wafers and semiconductors. The value of Si in crystalline-type photovoltaic modules is estimated to be -$95/kW at the 2012 metal price. At the current installed capacity of 30 GW/yr, the metal value in the PV modules represents valuable resources that should be recovered in the future. The recycling of end of-life photovoltaic modules would supply > 88,000 and 207,000 tpa Si by 2040 and 2050, respectively. This represents more than 50% of the required Si for module fabrication. Experimental testwork on crystalline Si modules could recover a > 99.98%-grade Si product by HNO3/NaOH leaching to remove Al, Ag, and Ti and other metal ions from the doped Si. A further pyrometallurgical smelting at 1520 degrees C using CaO-CaF2-SiO2 slag mixture to scavenge the residual metals after acid leaching could finally produce > 99.998%-grade Si. A process based on HNO3/NaOH leaching and subsequent smelting is proposed for recycling Si from rejected or recycled photovoltaic modules. Implications: The photovoltaic industry is considering options of recycling PV modules to recover metals such as Si, Ag, Cu, Al, and others used in the manufacturing of the PV cells. This is to retain its "green" image and to comply with current legislations in several countries. An evaluation of potential resources made available from PV wastes and the technologies used for processing these materials is therefore of significant importance to the industry. Of interest are the costs of processing and the potential revenues gained from recycling, which should determine the viability of economic recycling of PV modules in the future. PMID- 25122954 TI - Trends in on-road vehicle emissions and ambient air quality in Atlanta, Georgia, USA, from the late 1990s through 2009. AB - On-road vehicle emissions of carbon monoxide (CO), nitrogen oxides (NO(x)), and volatile organic compounds (VOCs) during 1995-2009 in the Atlanta Metropolitan Statistical Area were estimated using the Motor Vehicle Emission Simulator (MOVES) model and data from the National Emissions Inventories and the State of Georgia. Statistically significant downward trends (computed using the nonparametric Theil-Sen method) in annual on-road CO, NO(x), and VOC emissions of 6.1%, 3.3%, and 6.0% per year, respectively, are noted during the 1995-2009 period despite an increase in total vehicle distance traveled. The CO and NO(x) emission trends are correlated with statistically significant downward trends in ambient air concentrations of CO and NO(x) in Atlanta ranging from 8.0% to 11.8% per year and from 5.8% to 8.7% per year, respectively, during similar time periods. Weather-adjusted summertime ozone concentrations in Atlanta exhibited a statistically significant declining trend of 2.3% per year during 2001-2009. Although this trend coexists with the declining trends in on-road NO(x), VOC, and CO emissions, identifying the cause of the downward trend in ozone is complicated by reductions in multiple precursors from different source sectors. Implications: Large reductions in on-road vehicle emissions of CO and NO(x) in Atlanta from the late 1990s to 2009, despite an increase in total vehicle distance traveled, contributed to a significant improvement in air quality through decreases in ambient air concentrations of CO and NO(x) during this time period. Emissions reductions in motor vehicles and other source sectors resulted in these improvements and the observed declining trend in ozone concentrations over the past decade. Although these historical trends cannot be extrapolated to the future because pollutant concentration contributions due to on-road vehicle emissions will likely become an increasingly smaller fraction of the atmospheric total, they provide an indication of the benefits of past control measures. PMID- 25122955 TI - Annual and weekly patterns of ozone and particulate matter in Jeddah, Saudi Arabia. AB - Air pollution has been an increasing concern within the Kingdom of Saudi Arabia and other Middle Eastern countries. In this work the authors present an analysis of daily ozone (O3), nitrogen oxide (NO(x)), and particulate matter (< 10 miccrom aerodynamic diameter; PM10) concentrations for two years (2010 and 2011) at sites in and around the coastal city of Jeddah, as well as a remote background site for comparison. Monthly and weekly variations, along with their implications and consequences, were also examined. O3 within Jeddah was remarkably low, and exhibited the so-called weekend effect--elevated O3 levels on the weekends, despite reduced emissions of O3 precursors on those days. Weekend O3 increases averaged between 12% and 14% in the city, suggesting that NO(x)/volatile organic compound (VOC) ratios within cities such as Jeddah may be exceptionally high. Sites upwind or far removed from Jeddah did not display this weekend effect. Based on these results, emission control strategies in and around Jeddah must carefully address NO(x)/VOC ratios so as to reduce O3 at downwind locations without increasing it within urban locations themselves. PM10 concentrations within Jeddah were elevated compared with North American cites of similar climatology though comparable to other large cities within the Middle East. Implications: Daily concentrations of O3, PM10, and NO(x) in and around the city of Jeddah, Saudi Arabia, are analyzed and compared with those of other reference cities. Extremely low O3 levels, along with a significant urban weekend effect (higher weekend O3, despite reduced NO(x) concentrations), is apparent, along with high levels of PM10 within the city. Urban O3 in Jeddah was found to be lower than that of other comparable cities, but the strong weekend effect suggests that care must be taken to reduce downwind O3 levels without increasing them within the city itself. Further research into the emissions and chemistry contributing to the reduced O3 levels within the city is warranted. PMID- 25122956 TI - Carbon dioxide adsorption on amine-impregnated mesoporous materials prepared from spent quartz sand. AB - Mesoporous MCM-41 was synthesized using cetyltrimethyl ammonium bromide (CTAB) as a cationic surfactant and spent quartz sand as the silica source. Modification of the mesoporous structure to create an absorbent was then completed using 3 aminopropyltrimethoxysilane. Amine-Quartz-MCM (The A-Q-MCM) adsorbents were then characterized by N2 adsorption/desorption, elemental analysis (EA), X-ray fluorescence (XRF), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), as well as the carbon dioxide (CO2) adsorption/desorption performance. In this study, spent quartz sand was utilized to synthesize Quartz-MCM (Q-MCM) and the amine functionalized material, A-Q-MCM, which exhibited a higher uptake of CO2 at room temperature compared with the nongrafted material. The results showed that Q-MCM is similar to MCM-41 synthesized using commercial methods. The surface area, pore volume, and pore diameter were found to be as high as 1028 m2/g, 0.907 cm3/g, and 3.04 nm, respectively. Under the condition of CO2 concentration of 5000 ppm, retention time of 50 cc/min, and the dosage of 1 g/cm3, the mean adsorption capacity of CO2 onto A-Q-MCM was about 89 mg/g, and the nitrogen content of A-Q-MCM was 2.74%. The adsorption equilibrium was modeled well using a Freundlich isotherm. Implications: In this study, spent quartz sand was utilized to synthesize Q-MCM. The amine functionalized material exhibited a higher uptake of CO2 at room temperature compared with the nongrafted material. The results showed that Q-MCM is similar to MCM-41 synthesized using commercial methods. The adsorption equilibrium was modeled well using a Freundlich isotherm. PMID- 25122957 TI - Emission, speciation, and evaluation of impacts of non-methane volatile organic compounds from open dump site. AB - Surface emission from Dhapa, the only garbage disposal ground in Kolkata, is a matter of concern to the local environment and also fuels the issues of occupational and environmental health. Surface emission of the Dhapa landfill site was studied using a flux chamber measurement for nonmethane volatile organic compounds (NMVOCs). Eighteen noncarbonyl volatile organic compounds (VOCs) and 14 carbonyl VOCs, including suspected and known carcinogens, were found in appreciable concentrations. The concentrations of the target species in the flux chamber were found to be significantly higher for most of the species in summer than winter. Surface emission rate of landfill gas was estimated by using two different approaches to assess the applicability for an open landfill site. It was found that the emissions predicted using the model Land GEM version 3.02 is one to two orders less than the emission rate calculated from flux chamber measurement for the target species. Tropospheric ozone formation has a serious impact for NMVOC emission. The total ozone-forming potential (OFP) of the Dhapa dumping ground considering all target NMVOCs was estimated to be 4.9E+04 and 1.2E+05 g/day in winter and summer, respectively. Also, it was found that carbonyl VOCs play a more important role than noncarbonyl VOCs for tropospheric ozone formation. Cumulative cancer risk estimated for all the carcinogenic species was found to be 2792 for 1 million population, while the total noncancer hazard index (HI) was estimated to be 246 for the occupational exposure to different compounds from surface emission to the dump-site workers at Dhapa. Implications: This paper describes the real-time surface emission of NMVOCs from an open municipal solid waste (MSW) dump site studied using a flux chamber. Our study findings indicate that while planning for new landfill site in tropical meteorology, real-time emission data must be considered, rather than relying on modeled data. The formation of tropospheric ozone from emitted NMVOC has also been studied. Our result shows how an open landfill site acts as a source and adds to the tropospheric ozone for the airshed of a metropolitan city. PMID- 25122958 TI - A comprehensive study on landfill site selection for Kolkata City, India. AB - Kolkata is one of the four major metropolitan cities in India and the capital city of the state of West Bengal. With an area of 187.33 km2 and a population of about 10 million (including a floating population of about 6 million), the city generates about 3500 Metric Ton (MT) of solid waste per day. Currently, Kolkata Municipal Corporation (KMC) disposes its waste at Dhapa (21.47 ha), where the disposal rate exceeds 3000 MT/day, and at Garden Reach (3.52 ha), where the disposal rate is 100 MT/day. Considering the exhaustion of Dhapa land space, city planners are urgently searching for an alternate disposal ground. National Environmental Engineering Research Institute (NEERI), under the sponsorship of Central Pollution Control Board (CPCB), has brought out literature developing the site selection criteria for municipal solid waste disposal ground to suit Indian conditions. The developed criteria encompass environmental conditions, accessibility, geological and hydrogeological conditions, and ecological and societal effects. This paper attempts to locate the most suitable site for disposal of KMC area solid waste using the multicriterion decision analysis as stipulated in CPCB 2003 guidelines and the overlay analysis of geographic information system (GIS). Implications: The paper is based on landfill site selection for dumping of solid waste generated within Kolkata Municipal Corporation (KMC) area. The methodology uses GIS/remote sensing, Site Sensitivity Index (an offshoot of pairwise comparison technique developed in CPCB 2003 guidelines, Government of India), and the Delphi technique. Dhapa landfill site, where solid waste of KMC area is currently being disposed, is exhausted; the authors of this article thus found it relevant to carry out a research on the selection of an alternative landfill site. The study undertaken was comprehensive, yet presented in a lucid way so that policymakers will find easy to comprehend. PMID- 25122959 TI - A personal reflection on our future leaders. PMID- 25122960 TI - Generation to generation. Jesus, formation and transitions in leadership. PMID- 25122961 TI - CHI's formation initiatives. Programs help embed core values. PMID- 25122962 TI - Storytelling moves learning from head to heart to feet. PMID- 25122963 TI - The sounds of Project ECHO. PMID- 25122964 TI - Measuring ministry formation. Moving promise into practice. PMID- 25122965 TI - Tomorrow's Leaders, Class of 2014. PMID- 25122966 TI - Catching up with two leaders from the Class of 2011. PMID- 25122967 TI - Interview with Richard Gilfillan, MD. How leadership will empower ministry's move to population health. PMID- 25122968 TI - Preliminary results. CHA survey gauges formation effectiveness. PMID- 25122969 TI - Celebrating 100 years. PMID- 25122970 TI - The growth of systems. Unprecedented challenges. PMID- 25122971 TI - What we have here is a failure to communicate. The ethical dimension of health literacy. PMID- 25122972 TI - Add ethical decision-making to the planning process. PMID- 25122973 TI - Norms for canonical elections. PMID- 25122974 TI - Setting donation standards for surplus. PMID- 25122975 TI - Comparative plaque removal efficacy of two new powered toothbrushes and a manual toothbrush. AB - OBJECTIVE: The purpose of this study was to determine the plaque-reducing effectiveness of two new powered toothbrushes and compare them to a manual toothbrush control. METHODS: This examiner-blind, randomized study used a crossover design. Sixty-five qualifying male and female subjects were randomly assigned one of the two test powered brushes (Spinbrush Truly Radiant Deep Clean [TRDC] or Spinbrush Truly Radiant Extra Whitening [TREW], Church & Dwight Co., Inc., Princeton, NJ, USA) or an ADA standard manual toothbrush (MT; American Dental Association, Chicago, IL, USA) according to one of three computer generated sequences. Following instruction in the use of their assigned toothbrush, subjects brushed at home with a standard fluoride toothpaste twice daily for two minutes during a one-week familiarization period. At the end of this period, the subjects returned to the study site after refraining from oral hygiene for 12-16 hours, and from eating, drinking, and smoking for four hours. Plaque was scored using the Rustogi Modification of the Navy Plaque Index. Subjects brushed under supervision with their assigned toothbrush for two minutes, and plaque was rescored. They were then given one of the alternate toothbrushes according to their assigned sequence, and the familiarization routine and evaluation processes were repeated until each of the subjects used each of the three brushes. RESULTS: Within-group analyses showed that all three toothbrushes produced statistically significant reductions from the pre-brushing baseline in whole mouth and regional plaque scores (p < 0.001), with respective whole mouth reductions of 17.9%, 42.3%, and 38.1% for MT, TRDC, and TREW. Between group analyses showed that TRDC and TREW were each significantly more effective (p < 0.001) than MT, as each showed at least twice as much of a reduction in whole mouth scores. Both of the powered brushes also produced statistically significantly greater reductions than the manual brush at each of the twelve subsets of sites examined, with the greatest differences at interpoximal sites and sites presenting access difficulty, such as those in the lingual posterior region. Additionally, TRDC produced a statistically significant 11.5% greater reduction than TREW (p = 0.001) in whole mouth plaque scores, and statistically significantly greater reductions in two of the subsets evaluated. CONCLUSION: Both of the powered brushes tested proved to be safe and significantly more effective than the standard manual control brush in reducing plaque. While the finding that the TRDC was significantly more effective than the TREW in reducing whole mouth plaque and plaque in two subsets demonstrates that small differences in toothbrush design may impact performance, longer-term studies would be needed to assess the extent to which this translates to meaningful clinical outcomes. PMID- 25122976 TI - A six-week clinical evaluation of the plaque and gingivitis efficacy of an oscillating-rotating power toothbrush with a novel brush head utilizing angled CrissCross bristles versus a sonic toothbrush. AB - OBJECTIVE: To compare the efficacy of an oscillating-rotating power toothbrush with a novel brush head incorporating angled CrissCross bristles (Oral-B Triumph with SmartGuide with Oral-B CrossAction brush head) versus a sonic toothbrush (Sonicare DiamondClean) for plaque and gingivitis reduction over a six-week period. METHODS: This was a single-center, randomized, examiner-blind, two treatment, parallel group study involving 65 subjects per group. Subjects presenting with mild-to-moderate gingivitis at Baseline were randomly assigned to either the oscillating-rotating brush or the sonic brush. They were instructed to use their assigned toothbrush and a standard fluoride dentifrice for two minutes twice daily at home for six weeks. Gingivitis and plaque were assessed at Baseline and Week 6 using the Modified Gingival Index (MGI), Gingival Bleeding Index (GBI), and Rustogi Modified Navy Plaque Index (RMNPI). Data were analyzed using an Analysis of Covariance (ANCOVA), with baseline as the covariate. Subjects also completed a consumer perception questionnaire to evaluate their brushing experience. RESULTS: One-hundred and thirty subjects were enrolled in the study and randomized to treatment. Sixty-four subjects per group completed the trial. Both brushes produced statistically significant reductions in gingivitis and plaque measures at Week 6 relative to Baseline (p < 0.001 for all). The oscillating-rotating brush with the novel brush head demonstrated statistically significantly greater reductions in all gingivitis and plaque measures compared to the sonic toothbrush. The benefits for the oscillating rotating brush over the sonic brush were 32.6% for gingivitis, 35.4% for gingival bleeding, 32% for number of bleeding sites, 22% for whole mouth plaque, 24.2% for gingival margin plaque, and 33.3% for approximal plaque (p < or = 0.001 for all measures except gingival margin plaque, where p = 0.018). Analysis of the consumer perception questionnaire results showed subjects using the oscillating rotating brush rated it higher for overall use experience and key attributes related to cleaning, gentleness, and brush head shape/size versus subjects in the sonic brush group. There were no adverse events reported or observed for either brush. CONCLUSION: This six-week randomized, examiner-blind, comparative clinical study showed the oscillating-rotating toothbrush, with a novel brush head incorporating angled CrissCross bristles, was significantly better than an advanced sonic power toothbrush at reducing gingival inflammation and bleeding, as well as reducing whole mouth plaque, plaque along the gumline, and in the approximal regions. PMID- 25122977 TI - A clinical study to assess the effect of a stabilized stannous fluoride dentifrice on hypersensitivity relative to a marketed sodium fluoride/triclosan control. AB - OBJECTIVE: To evaluate the efficacy of a marketed stabilized stannous fluoride (SnF2) dentifrice in reducing dentinal hypersensitivity as compared to a marketed sodium fluoride (NaF)/triclosan dentifrice over an eight-week period. METHODS: Adults with confirmed dentinal hypersensitivity were enrolled in this randomized and controlled, parallel group, double blind, eight-week, single-center clinical trial. Random assignment to one of two dentifrice test groups via age, gender, and thermal sensitivity of enrolled test teeth was performed at baseline, with subjects assigned to twice-daily unsupervised brushing with either the marketed SnF2 dentifrice (Oral-B Pro-Expert, 0.454% SnF2 plus 0.077% NaF) or the marketed 0.32% NaF with 0.3% triclosan/copolymer dentifrice control (Colgate Total Advanced). Tactile sensitivity (Yeaple Probe) and thermal sensitivity (airblast/Schiff Air Index) evaluations of the selected test teeth were performed at baseline pre-treatment, and again at Weeks 2 and 8 of product use to compare the dentifrices' relative hypersensitivity protection effectiveness. RESULTS: Ninety-seven (97) of the 100 enrolled subjects completed the trial and were fully evaluable. At both Week 2 and Week 8, for both the thermal and tactile evaluation measurements, subjects brushing with the marketed SnF2 dentifrice experienced statistically significantly (p < 0.0001) superior average dentinal hypersensitivity improvement versus subjects assigned to the NaF/triclosan control dentifrice. Between groups, superior relative mean reduction in thermal Schiff Air Index favored SnF2 by 24% at Week 2 and 68% at Week 8, while greater relative mean tactile Yeaple Probe benefits were observed for SnF2 relative to the control by 114% after Week 2 and 184% at Week 8. The dentifrices were well tolerated. CONCLUSION: Twice-daily brushing with a marketed SnF2 dentifrice provided superior dentinal hypersensitivity improvement versus a commercially available NaF/triclosan dentifrice, with significantly (p < 0.0001) greater relief after two weeks, and even larger relative benefits at eight weeks. PMID- 25122978 TI - Brush head composition, wear profile, and cleaning efficacy: an assessment of three electric brush heads using in vitro methods. AB - OBJECTIVE: The objective of this research was to evaluate a current store brand (SB) brush head for composition/physical characteristics, Wear Index (WI), and cleaning efficacy versus the previous SB brush head refill design (SB control) and the Oral-B Precision Clean brush head (positive control, PC). METHODS: This research consisted of three parts: 1) Analytical analysis using Fourier Transform Infrared (FT-IR) spectrometry to evaluate the chemical composition of the current SB brush head bristles relative to the SB control. In addition, physical parameters such as bristle count and diameter were determined. 2) Wear Index (WI) investigation to determine the Wear Index scores of in vitro-aged brush heads at four weeks (one month) and 13 weeks (three months) by a trained investigator. To "age" the brush heads, a robot system was used as a new alternative in vitro method to simulate aging by consumer use. 3) Robot testing to determine the cleaning performance of in vitro-aged brush heads, comparing one month-aged current SB brush heads with the SB control (one and three months-aged) and the PC brush heads (three months-aged) in a standardized fashion. RESULTS: 1) FT-IR analysis revealed that the chemical composition of the current and control SB refill brush heads is identical. In terms of physical parameters, the current SB brush head has 12% more bristles and a slightly oval brush head compared to the round brush head of the SB control. 2) Wear Index analysis showed there was no difference in the one month-aged current SB brush head versus the one month-aged SB control (1.67 vs. 1.50, p = 0.65) or versus the three months-aged PC brush head (1.67 vs. 1.50, p = 0.65). The one month-aged current SB brush head demonstrated statistically significantly less wear than the three months-aged SB control (1.67 vs. 2.67, p = 0.01). 3) Analysis of cleaning efficacy shows that the one month-aged current SB brush head had improved cleaning performance over the one month-aged SB control brush head (p < 0.05), despite no statistically significant difference in wear. Both the one month-aged current and control SB brush heads showed statistically significantly lower cleaning performance compared to the three months-aged PC brush heads (p < 0.01). CONCLUSION: While the current SB brush head showed improved cleaning over the SB control, it demonstrated significantly lower durability and cleaning in comparison to the PC brush head. Dental professionals should be aware of these differences, both in durability and in cleaning performance, when recommending brush heads to their patients. PMID- 25122979 TI - A randomized 12-week clinical comparison of an oscillating-rotating toothbrush to a new sonic brush in the reduction of gingivitis and plaque. AB - OBJECTIVE: To evaluate the efficacy of a marketed oscillating-rotating (O-R) power toothbrush (Oral-B Triumph with SmartGuide and FlossAction brush head, D34/EB25) to a new sonic toothbrush (Sonicare FlexCare Platinum) in the reduction of gingivitis and plaque over a 12-week test period. METHODS: This was a single center, randomized, open label, examiner-blind, two-treatment, parallel group study. Subjects who met the entrance criteria were enrolled in the study and randomly assigned to either the O-R or sonic treatment group. Subjects brushed with their assigned toothbrush and a marketed fluoride dentifrice for two minutes twice daily at home for 12 weeks. Gingivitis and plaque were evaluated at Baseline, Week 6, and Week 12. Gingivitis was assessed using the Modified Gingival Index (MGI) and Gingival Bleeding Index (GBI), and plaque was assessed using the Rustogi Modified Navy Plaque Index (RMNPI). Data were analyzed using an Analysis of Covariance (ANCOVA) with Baseline as the covariate. RESULTS: In total, 130 subjects (65 per group) were randomized to treatment and 127 subjects completed the study. Both brushes produced statistically significant (p < 0.001) reductions in gingivitis and plaque measures relative to Baseline. At Week 12, the O-R brush demonstrated significantly greater reductions than the sonic brush in whole mouth gingivitis measures (p = 0.007). Additionally, the O-R brush presented significantly fewer bleeding sites (p < 0.007) and significantly greater reductions in whole mouth plaque measures (p < or = 0.035) at Weeks 6 and 12 versus the sonic brush. The benefit for the O-R brush versus the sonic brush at Week 12 was 11.7% for gingivitis, 19.8% for number of bleeding sites, and 12.2% for whole mouth plaque. There were no adverse events reported or observed for either brush. CONCLUSION: The oscillating-rotating toothbrush demonstrated statistically significantly greater reductions in whole mouth plaque at Weeks 6 and 12, as well as significantly greater gingivitis reductions over the long-term (12 weeks), compared to the new sonic toothbrush. PMID- 25122980 TI - A clinical study of the efficacy of a new chewing gum containing calcium hydroxyapatite in reducing dentin hypersensitivity. AB - OBJECTIVE: A controlled, clinical, double blind study was conducted to assess the efficacy of a sugar-free chewing gum containing calcium hydroxyapatite on dentin hypersensitivity, versus a placebo chewing gum with no active ingredients, after one and two weeks. METHODS: One hundred and seven subjects joined the trial and were allocated into the test or the control (placebo) group by a random table. The test chewing gum contained calcium hydroxyapatite and dicalcium phosphate dihydrate; the control chewing gum was identical, but without those ingredients. Participants were required to chew two pieces of their assigned chewing gum three times a day. Dentin hypersensitivity was evaluated following three clinical test indexes (tactile, air blast, cold water) and one subjective index. RESULTS: One hundred subjects completed the study with 50 allocated to each group. The clinical test index reductions after one and two weeks in the test group were, respectively, 36% and 54% for tactile, 35% and 66% for air blast, and 24% and 49% for cold water. The clinical test index reductions after one and two weeks in the control group were, respectively, 16% and 30% for tactile, 11% and 25% for air blast, and 14% and 31% for cold water. These reductions at one and two weeks were significant for the test group (p < 0.01). For the control group they were significant (p < 0.01) only at two weeks. The comparisons between the groups at two weeks showed a significant statistical difference between the test and the control gum for tactile (p < 0.01), for air blast (p < 0.001), for cold water (p < 0.05), and for the subjective index (p < 0.05). CONCLUSION: In this trial, the group using the chewing gum containing calcium hydroxyapatite had a statistically significant reduction in all clinical test indexes for dentin hypersensitivity after one and two weeks, and a statistically significant reduction compared to the control gum group. PMID- 25122981 TI - Psychotherapy supervision developments and innovations for the new millennium: contributions from the cutting edge. AB - What are some of the most recent, cutting-edge developments and innovations in psychotherapy supervision? And what is their particular significance for supervision now and into its future? In this special supervision issue of the American Journal of Psychotherapy, those questions are considered, and some compelling answers are provided. In what follows, I introduce this special journal issue: (a) define supervision and indicate its purposes; (b) summarize the contents of each innovative paper; and (c) accentuate the significance of each presented development/innovation. The papers contained in this issue boldly speak to supervision's future and provide exciting--and highly profitable- directions to pursue in forever making psychotherapy supervision a far more anchored, accountable, and educational experience. PMID- 25122982 TI - Best Practices in Clinical Supervision: another step in delineating effective supervision practice. AB - Across the helping professions, we have arrived at a point where it is possible to create statements of best practices in supervision that are based on available empirical research; credentialing, ethical, and legal guidelines; and consensus opinion. Best practices are different from, but certainly complementary to, statements of supervision competencies. In this paper, I highlight the differences between competencies and best practices, and then describe the development and content of one comprehensive statement, the Best Practices in Clinical Supervision created for the field of counseling and counselor education. I then illustrate the applicability of the Best Practices across disciplines and countries through a comparison and contrast with several other existing documents. I conclude with a brief look at the development of supervisor expertise, which requires not only declarative knowledge (competencies) and procedural knowledge (statements of best practices), but also reflective knowledge. The latter is composed of insights built over years of supervision education, experience, and self-reflection regarding necessary adaptions and improvisations that inform an individualized approach to supervision practice. PMID- 25122983 TI - Using learning objectives for psychotherapy supervision. AB - Although learning objectives, often in the form of competencies, are now standard for training mental health professionals, they are not generally used to guide psychotherapy supervision. Nevertheless, when learning objectives are not used to guide supervision, supervisors and supervisees often remain uncertain about the goals of supervision, how those goals should be attained, and how they should be assessed. In this paper we review the literature on learning objectives for psychotherapy training and supervision, outline reasons for using learning objectives in psychotherapy supervision, and suggest ways to use learning objectives in training. PMID- 25122984 TI - Evaluation of psychology practitioner competence in clinical supervision. AB - There is a growing consensus favouring the development, advancement, and implementation of a competency-based approach for psychology training and supervision. There is wide recognition that skills, attitude-values, and relationship competencies are as critical to a psychologist's competence as are knowledge capabilities, and that these key competencies are best measured during placements, leaving the clinical supervisor in an unparalleled position of advantage to provide formative and summative evaluations on the supervisee's progression towards competence. Paradoxically, a compelling body of literature from across disciplines indicates that supervisor ratings of broad domains of competence are systematically compromised by biases, including leniency error and halo effect. The current paper highlights key issues affecting summative competency evaluations by supervisors: what competencies should be evaluated, who should conduct the evaluation, how (tools) and when evaluations should be conducted, and process variables that affect evaluation. The article concludes by providing research recommendations to underpin and promote future progress and by offering practice recommendations to facilitate a more credible and meaningful evaluation of competence and competencies. PMID- 25122985 TI - The use of supervision notes as a targeted training strategy. AB - Despite a call for more training of clinical supervisors, little has emerged in the professional literature to offer pedagogical strategies for training. This article describes the use of supervision documentation to guide the development of supervisors-in-training (SITs). Specifically, supervision notes are used to assist and monitor SITs understanding and application of supervisor models. PMID- 25122986 TI - Beyond the "acid test": a conceptual review and reformulation of outcome evaluation in clinical supervision. AB - Theoretical models abound within clinical supervision, but these rarely have been applied to supervision evaluation. Instead, it appears that reviewers and researchers have simply transferred to supervision the conceptual frameworks used within medicine, especially the idea that clinical outcomes are the "acid test" of supervisory effectiveness or quality. Following a careful examination of the key literature, in this paper I argue that this has led to an over-emphasis on clinical outcomes, with the net effect of reducing scientific confidence, understanding, and the effectiveness of supervision. To begin to rectify this bias, an augmented fidelity framework is used to reformulate evaluation, drawing on some of the key concepts guiding evaluation within related fields (i.e. service evaluation; staff development; psychotherapy; applied research). The resulting evaluation model is specific to clinical supervision and can help to increase our understanding, enhance our practice, re-prioritise research, and inspire confidence in supervision. PMID- 25122987 TI - Videoconference for psychotherapy training and supervision: two case examples. AB - Psychotherapy supervision and training are now widely available online. However, many supervisors still may be unclear on how online supervision actually works, or what it actually looks like in practice. In this article, three case examples of online videoconference-based supervision programs will be described. Partial transcripts from two online supervision sessions are provided. The benefits and limitations of online supervision are discussed, including discussion of supervision process, ethics, privacy, and security. PMID- 25122988 TI - Clinical supervision in the 21st century: revisiting pressing needs and impressing possibilities. AB - What are some of the most pressing needs currently confronting clinical supervision? In this paper, I give attention to that question. Drawing on two 1990 reviews for comparative purposes, I examine where supervision is now relative to four areas: (a) supervision training and practice; (b) measurement; (c) difference and diversity; and (d) research. Lines of advance, pressing needs, and potential remedies are considered across each area. Effort is made to accentuate the "robustly international" nature of clinical supervision and its increasing globalization. PMID- 25122989 TI - [The medicolegal relevance of benign and malignant coronary artery anomalies]. AB - Isolated coronary anomalies are rare abnormalities that can be divided into benign and malignant forms. Malignant coronary artery abnormalities generally present already during infancy or early childhood by causing symptoms or sudden death. Benign abnormalities often remain asymptomatic because they are hemodynamically irrelevant. Among the 12,985 autopsies performed at the Institute of Legal Medicine at the University of Frankfurt (Germany) between 1995 and 2013, there were eight cases (0.062%) with isolated coronary artery abnormalities. Five of these cases (0.039%) could be included in our retrospective study. These involved one deceased female and four deceased male subjects, aged between 2 and 57 years. In three of these cases (aged 6, 9, and 11 years old), the coronary anomaly was classified as malignant and was recorded as the cause of death. Benign isolated coronary anomalies are often incidental findings during autopsies. However, in one of the cases in our study, coronary sclerosis in precisely the anomalous vessel was found to be the origin of a fatal myocardial infarction. Malignant isolated coronary artery anomalies attain medicolegal significance when they remain undetected despite advanced early detection protocols and cause sudden death in childhood. PMID- 25122990 TI - [Cause and manner of death in the autopsy material of the Institute of Forensic Medicine, Justus Liebig University Giessen, from 2002-2006]. AB - A retrospective analysis of the autopsy material of the Institute of Forensic Medicine, Justus Liebig University Giessen, in the years 2002 to 2006 showed that the Giessen material is similar to that of comparable studies but contains a relatively large share of lethal intoxications and cases with a concrete suspicion of poisoning in which the cause of death was not definitely clarified by further investigations. On the basis of our own results it is demonstrated that additional chemical, toxicological and histological examinations are helpful to determine initially unclear causes of death. In view of the already very low autopsy rates in Germany it is strange that more detailed diagnostic measures are often omitted. PMID- 25122991 TI - [Hans Gross as an archaeologist--the significance of archaeology for 'encyclopedic' criminology]. AB - In some cases, forensics and criminology have to cooperate with disciplines that usually are counted among the humanities, e.g. with archaeology. This article examines the significance of this cooperation for the criminological epistemology at the turn of the 19th century. These methodological considerations are illustrated by an example: When Hans Gross, who became the founder of the Austrian School of Criminology later, saw an unusually shaped hill near Feldbach, a town in southern Styria, he assumed this hill to be a burial mound and informed the responsible archaeological authorities immediately. Further investigations showed, however, that this hill was a natural formation. This is an early example for interdisciplinary cooperation, which proves that both in archaeology and in criminology a thorough inspection of the site is decisive for further scientific analysis of the topic of research. PMID- 25122992 TI - [Intentional poisoning of two wives by their husband?]. AB - The authors report on the death of two women who were married to the same man one after the other. Exhumation and toxicological investigation of the first wife, who had died 7 years before, did not produce any conclusive evidence of homicide. With regard to the circumstances of death of the second wife the husband made different statements. According to the result of the chemical and toxicological investigations death was caused by acute intoxication with the beta-blocker metoprolol. The man was found guilty of killing on request (which is a criminal offence in Germany) by administering the beta-blocker metoprolol through a transnasal gastric tube. PMID- 25122993 TI - [Hand injuries by pyrotechnic articles--case report and reconstructive experimental investigations]. AB - Injuries caused by explosions of fireworks often involve people's hands. The case of a young man who suffered severe hand injuries as well as damage to both eardrums and one eye is described. Reconstructive experimental investigations of the explosive effect of six different pyrotechnic articles were carried out using human hands from body donors. With the most powerful firecrackers that used to be legally available in Germany ("Super-Boller A", "Kanonenschlag") and a self-made one with 36 g gunpowder only blackening of the skin occurred. Three pyrotechnic articles not allowed in Germany ("La Bomba", "Color salute" and "Vogelschreck") caused serious injury to the hand's soft tissue and bones. PMID- 25122994 TI - [Cranial CT as basis for reconstruction of events and identification of a weapon]. AB - Radiological findings, especially CT scans, are of great importance in the reconstruction of events and may also be helpful to identify the weapon used. This is illustrated by a briefly survived craniocerebral trauma whose origin was controversially discussed. A 51-year-old man had suffered a severe craniocerebral trauma in a robbery. The CT scans revealed fractures of the left parietal region, among them a spider's web fracture, on the cause of which opinions differed (fall or blow). It was also unclear which of the three confiscated objects (empty wine bottle, bending iron, wooden hammer) was used for the assault. Evaluation of the CT findings showed that at least two blows had obviously been inflicted to the cranial skull. Apart from several injuries of the scalp due to blows, the typical combination of findings in the occipital region and contre-coup lesions suggested that the head had also hit the ground due to a fall. The soft tissue injuries may have been caused by all the three confiscated objects. The bony injuries were most probably caused by the bending iron, whereas the wooden hammer and the wine bottle could be ruled out as the causative weapon or were at least highly improbable. PMID- 25122995 TI - Effect of chainring ovality on joint power during cycling at different workloads and cadences. AB - Non-circular chainrings theoretically enhance cycling performance by increasing effective chainring diameter and varying crank velocity, but research has failed to consistently reproduce the benefits in cycling trials. The aim of this study was (1) to investigate the effect of different chainring shapes on sagittal knee joint moment and sagittal lower limb joint powers and (2) to investigate whether alterations are affected by cadence and workload. Fourteen elite cyclists cycled in six conditions (70, 90 and 110 rpm, each at 180 and 300 W), for 2 min each, using three chainrings of different ovalities (1.0-1.215). Kinematic data and pedal forces were collected. For most conditions, only the chainring with the highest ovality (1.215) was characterised by smaller sagittal knee joint moments, smaller relative sagittal knee joint power contribution and larger relative sagittal hip joint power contribution, which suggests a change from maximising efficiency to maximising power production. Effect sizes increased with higher cadences, but not with higher workload. This study has application for athletes, clinicians and sports equipment industry as a non-circular chainring can change joint-specific power generation and decrease knee joint moment, but certain ovality seems to be necessary to provoke this effect. PMID- 25122996 TI - Grip pressure distributions and associated variability in golf: a two-club comparison. AB - Teaching and playing professionals offer multiple theories concerning the manner in which forces should be applied to the handle of the club during the golf swing. This study extends recent research concerning grip pressures and forces in golf, with the purpose of exploring the similarities and differences between force profiles for a 7-iron and driver swung by proficient golfers. A secondary purpose was to further analyze the way that golfers use grip forces to manipulate the club. Grip forces were measured on eight low handicap golfers (USGA indexes 0 to 7) swinging their own 7-irons and drivers. In total, lead-hand and trail-hand grip forces were isolated as well as anatomically specific forces within the hands. Force profile variability across multiple swings for each golfer and between golfers characterized consistencies and important differences. Correlations between 7-iron and driver force profiles characterized force 'signatures.' The data highlight large fluctuations in grip forces during the swing. Marked differences between participants were observed, involving force magnitudes and phasing. Dominant forces arose primarily from the lead hand, specifically the last three fingers. Force profiles were highly repeatable across swings for a golfer (standard deviations < 7% of total force) and force profile correlations between 7-iron and driver for a golfer were remarkably high (r2 = 0.86). Notably, within swing force variability was greatest during club acceleration, but dramatically decreased at impact. PMID- 25122997 TI - Musculoskeletal loading during the round-off in female gymnastics: the effect of hand position. AB - Chronic elbow injuries from tumbling in female gymnastics present a serious problem for performers. This research examined how the biomechanical characteristics of impact loading and elbow kinematics and kinetics change as a function of technique selection. Seven international-level female gymnasts performed 10 trials of the round-off from a hurdle step to flic-flac with 'parallel' and 'T-shape' hand positions. Synchronized kinematic (3D-automated motion analysis system; 247 Hz) and kinetic (two force plates; 1,235 Hz) data were collected for each trial. Wilcoxon non-parametric test and effect-size statistics determined differences between the hand positions examined in this study. Significant differences (p < 0.05) and large effect sizes (ES > 0.8) were observed for peak vertical ground reaction force (GRF), anterior-posterior GRF, resultant GRF, loading rates of these forces and elbow joint angles, and internal moments of force in sagittal, transverse, and frontal planes. In conclusion, the T-shape hand position reduces vertical, anterior-posterior, and resultant contact forces and has a decreased loading rate indicating a safer technique for the round-off. Significant differences observed in joint elbow moments highlighted that the T-shape position may prevent overloading of the joint complex and consequently reduce the potential for elbow injury. PMID- 25122998 TI - An analysis of two styles of arm action in the vertical countermovement jump. AB - The aim of this study was to determine the effect of two arm swing techniques, the simultaneous arm swing and the early arm swing, on vertical countermovement jump performance and on the contribution of the arms to vertical movement at the centre of mass (CM) during the propulsion phase. Participants were 28 athletes practicing sports in which the vertical jump constitutes a basic ability. Ground reaction forces were recorded by a force platform and the sagittal plane motion was recorded by a video camera. Although at take-off the vertical velocity (2.7 +/- 0.2m/s for simultaneous technique vs. 2.8 +/- 0.2m/s for early technique; p = 0.040) and position (1.18 +/- 0.06m for simultaneous vs. 1.17 +/- 0.05m for early; p = 0.033) of the CM were significantly different, no difference was observed in jump height (1.56 +/- 0.01m in both techniques). The arm action differed during the initial and final propulsion phases in both styles but the accumulated vertical contribution was similar. The practical implication in sports is that the use of the arm-swing technique to reach the maximum jump height should be determined by tactical demands instead of the technical execution of the arms. PMID- 25122999 TI - Comparison of support leg kinetics between side-step and cross-step cutting techniques. AB - The purpose of this study was to investigate differences in the support leg joint moment and moment power between side-step (SS) and cross-step (CS) cutting techniques with a prescribed 90 degrees cutting angle. Ground reaction forces (1,000Hz) and three-dimensional kinematics (250Hz) of SS and CS cutting techniques were collected from 20 male college athletes. Normalised peak knee extension moment was larger in the SS technique than in the CS technique (0.40 +/ 0.10 in SS; 0.26 +/- 0.08 in CS). In the SS technique, the knee extensors (-0.10 +/- 0.06 in SS; -0.02 +/- 0.04 in CS) and ankle plantarflexors (-0.12 +/- 0.05 in SS; -0.07 +/- 0.03 in CS) did significantly more negative work (normalised). The direction change angle (40.5 +/- 8.7 degrees in SS; 33.0 +/- 6.8 degrees in CS) and the decrease in horizontal velocity of the centre of mass (-0.63 +/- 0.23 m/s in SS; -0.31 +/- 0.23 m/s in CS) were significantly larger in the SS technique. These results suggest that the SS technique is an effective means of changing running direction at the expense of velocity of the centre of mass and that the CS technique is better for minimising the reduction in horizontal velocity of the centre of mass. PMID- 25123000 TI - Is starting with the feet out of the water faster in backstroke swimming? AB - This study aimed to determine if starting with the feet above the water (FAW) in male backstroke swimming resulted in faster start times (15-m time) than when the feet were underwater (FUW). It was hypothesised that setting higher on the wall would generate increased horizontal force and velocity, resulting in quicker starts. Twelve high-level male backstrokers performed three trials of the FAW and FUW techniques. A biomechanical swimming testing system comprising one force plate (1,000 Hz), four lateral-view (100Hz), and five overhead (50Hz) video cameras captured the swimmers' performance. Data for each participant's fastest trial for each technique were collated, grouped, and statistically analysed. Analysis included Wilcoxon, Spearman Rho correlation, and regression analysis. Wilcoxon results revealed a significantly faster start time for the FAW technique (p < 0.01). Peak horizontal force was significantly smaller for FAW (p = 0.02), while take-off horizontal velocity was significantly greater (p = 0.01). Regression analysis indicated take-off horizontal velocity to be a good predictor of start time for both techniques, and the horizontal displacement of the centre of mass for the FAW start. PMID- 25123001 TI - Scapulothoracic kinematics during tennis forehand drive. AB - Scapular dyskinesis is recognized as an abnormality in the kinetic chain; yet, there has been little research quantifying scapular motion during sport tasks. Tennis forehand drives of eight highly skilled tennis players were studied to assess the scapulothoracic kinematics and evaluate repeatability using video based motion analysis. Scapulothoracic downward/upward rotation, posterior/anterior tilt, and internal/external rotation were computed using an acromial marker cluster. On average, the upward rotation, anterior tilt, and internal rotation varied from 1 degrees to 26 degrees, from 7 degrees to 32 degrees, and from 42 degrees to 100 degrees, respectively, during the tennis forehand drive. During the backswing and forward swing phases of the forehand stroke, small changes were observed for the three scapular angle values, while all angles increased rapidly during the follow-through phase. This suggests that the tennis forehand drive may contribute to scapula dyskinesis, mainly due to the great amplitude in scapulothoracic anterior tilt and internal rotation observed during the follow-through phase. Knowledge of normal scapula motion during sport tasks performed at high velocity could improve the understanding of various sport specific adaptations and pathologies. PMID- 25123002 TI - Unsteady flow phenomena in human undulatory swimming: a numerical approach. AB - The undulatory underwater sequence is one of the most important phases in competitive swimming. An understanding of the recurrent vortex dynamics around the human body and their generation could therefore be used to improve swimming techniques. In order to produce a dynamic model, we applied human joint kinematics to three-dimensional (3D) body scans of a female swimmer. The flow around this dynamic model was then calculated using computational fluid dynamics with the aid of moving 3D meshes. Evaluation of the numerical results delivered by the various motion cycles identified characteristic vortex structures for each of the cycles, which exhibited increasing intensity and drag influence. At maximum thrust, drag forces appear to be 12 times higher than those of a passive gliding swimmer. As far as we know, this is the first disclosure of vortex rings merging into vortex tubes in the wake after vortex recapturing. All unsteady structures were visualized using a modified Q-criterion also incorporated into our methods. At the very least, our approach is likely to be suited to further studies examining swimmers engaging in undulatory swimming during training or competition. PMID- 25123003 TI - Comparisons of the latching on between newborns with tongue-tie and normal newborns. AB - BACKGROUND: Breastfeeding is recommended as the exclusive feeding for the first six months of the newborns life. Difficulty in latching and breastfeeding resulting from tongue-tie are believed to be a problem. OBJECTIVE: To compare the latching on between newborns with tongue-tie (ankyloglossia) and normal newborns. MATERIAL AND METHOD: The subjects were 833 normal, postpartum women who delivered without complications at HRH Princess Maha Chakri Sririndhorn Medical Center in Nakhon Nayok Province between January and June 2013. Their newborns oral cavities' were checked for tongue-tie screening and diagnoses using Kotlow's criteria. Latch scores were used for latch-on assessment at the second day postpartum. Demographic data and latch scores were collected and analyzed by the t-test, Chi-square test, Odds ratio with 95% confidence interval and One-way of ANOVA test. RESULTS: The data shows that the incidence of tongue-tie was 13.4% (6.2% with mild tongue-tie, 5.5% with moderate tongue-tie, and 1.7% with severe tongue-tie). The mean of latch scores in the tongue-tied groups were significantly lower than that in the normal group, especially in the moderate and severe tongue-tie subgroups. The odds ratios for latch scores were < or = 8 compared between the moderate and severe tongue-tied subgroups and the score in the normal and mild tongue-tied subgroups was 1.4. CONCLUSION: The latch scores in tongue-tied newborns were significantly lower than those in normal newborns. PMID- 25123004 TI - Management and clinical outcomes of endometrial hyperplasia during a 13-year period in Songklanagarind Hospital. AB - BACKGROUND: Endometrial hyperplasia has long been considered a precursor of endometrial cancer but there is no consensus regarding its management. OBJECTIVE: To identify management practices and evaluate outcomes of treatments for women diagnosed with endometrial hyperplasia (EH). MATERIAL AND METHOD: The medical records of endometrial hyperplasia at Songklanagarind Hospital between January 2000 and December 2012 were retrospectively reviewed. RESULTS: Two hundred ninety seven patients were diagnosed with endometrial hyperplasia during the study period. Four patients who did not come for treatment and could not be contacted were excluded Therefore, 293 patients were included in the study. Simple hyperplasia (SH) was the most common diagnosis accounting for 79.2% of all cases, followed by complex hyperplasia (CH) 13.0%, complex atypical hyperplasia (CAH) 5.8%, and simple atypical hyperplasia (SAH) 2.0%. Seventy-eight percent (18/23) of the patients with atypical endometrial hyperplasia were treated by hysterectomy compared with 9.6% (26/270) of patients without atypia. Of the patients diagnosed with atypical EH, 30.4% (7/23) were associated with endometrial carcinoma. Overall, 6% (12/201) of the women who had initial non hysterectomy management and had additional tissue taken to assess response, had persistent disease, and 1% (2/201) had progressive disease. Eleven patients (5.9%), who had an initial complete regression during the non-hysterectomy management, experienced a recurrence to EH and 2.1% (4/187) were found to have recurrence to endometrial cancer CONCLUSION: The majority of patients with atypical hyperplasia were managed by initial hysterectomy. The high risk of concomitant endometrial cancer supports this choice of treatment. In the non atypical EH, the initial non-hysterectomy management was common but EH recurrence and progression to endometrial cancer after the initial regression occurs often. Therefore, long-term follow-up should be advised. PMID- 25123005 TI - Nomogram of placental thickness, placental volume and placental vascular indices in healthy pregnant women between 12 and 20 weeks of gestation. AB - OBJECTIVE: To generate the nomogram of placental thickness, volume, and vascular indices in healthy pregnant women between 12 to 20 weeks of gestation. MATERIAL AND METHOD: An experimental cross sectional study of pregnant women, which were categorized into nine groups according to their gestational age ranging from 12 to 20 weeks of gestation, was done. Placental parameters that included placental thickness, volume, and vascular indices were measured using a Voluson E8 ultrasound machine. The measurements were correlated with gestational age. RESULTS: Two hundred ninety four subject were included in this study. The study indicated that the placental thickness and volume significantly increased with gestational age (r = 0.481, p < 0.001 and r = 0.837, p < 0.001). The correlation between the placental volume and gestational age can be formulated according to this equation: Placental volume (cm3) = e7.584-42.45(1/GA); R2 = 0.76. Nonetheless, there is a very low correlation between the vascularization index (VI), vascularization flow index (VFI), and the gestational age (r = 0.162, p = 0.005 and r = 0.158, p = 0.007). The flow index (FI) was shown to have no correlation with gestational age (r(p) = -0.067, p = 0.254). CONCLUSION: From the present study, the placental thickness and placental volume significantly increased with gestational age. The VI and VFI showed poor correlation with gestational age while the FI had no correlation with the gestational age. PMID- 25123006 TI - Radiation, chemotherapy or combined modality therapy in adjuvant treatment for stage III endometrial carcinoma in lower southern Thailand: disease recurrence and overall survival. AB - OBJECTIVE: To survey disease-free survival (DFS) and overall survival (OS) of patients with stage III endometrial carcinoma treated with post-operative radiation and/or chemotherapy MATERIAL AND METHOD: The medical records of patients with surgical stage III endometrial carcinoma, and receiving adjuvant treatment between January 2003 and December 2012 were reviewed DFS and OS were analyzed using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: Of the 54 eligible patients, 61% underwent radiation, 19% chemotherapy, and 20% chemotherapy with radiation. The median DFS was 36.7 months. The 3-year DFS and OS was 51.9% (95% CI 36.3-74.1%) and 70.6% (95% CI 57.4-86.8%), respectively. There was no significant difference in DFS and OS among treatment groups. Cox regression analysis showed grade 2-3 tumors and menopause were associated with poor DFS and OS. CONCLUSION: The DFS and OS in stage III endometrial carcinoma receiving postoperative adjuvant therapy were quite good and were not different among radiation therapy, chemotherapy, and combined treatment groups. The multi-center randomized prospective study was needed to determine the standard modality. PMID- 25123007 TI - Burden of adult pneumonia in Thailand: a nationwide hospital admission data 2010. AB - OBJECTIVE: To quantify the admission mortality, pathogens,factors related to mortality, length of hospital stay, and healthcare costs in adult hospitalized pneumonia in Thailand MATERIAL AND METHOD: The data on hospitalized pneumonia for the 2010 fiscal year extracted from the three main health insurance coverage schemes in Thailand (the Social Security System (SSS), the Medical Welfare System (MWS), and the Civil Servant Medical Benefit System (CSMBS)) were analyzed RESULTS: Adult hospitalized pneumonia admissions numbered 136,696, with mortality rate 9.63%. The mortality increased with increasing age, 15.49% for age > 80 years. Influenza virus was the major etiology for 19 to 25 years old (49.30%) with low mortality (1-2%). S. pneumoniae and typical pathogens were found in every age group. The mortality rate for S. pneumoniae increased with age, viz. 0%, 1.96%, 5.56%, 7.02%, 6.98%, and 24.24% for 19 to 25, 26 to 40, 41 to 60, 61 to 70, 71 to 80, and 81+ years old. The mortality rate from C. pneumonia was about 10% and high among the younger age group. Gram-negative bacilli and Staphylococcus caused high mortality (about 20 to 35%), especially in the older age group. The major risk factors for increasing mortality were: elderly (OR 3.46, 95% CI 3.27-3.77), alcoholic liver disease (OR 3.26, 95% CI 2.85-3.72), cirrhosis (OR 3.45, 95% CI 2.93-4.08), heart disease (OR 2.47, 95% CI 2.38-2.56), ischemic heart disease (OR 2.21, 95% CI 2.07-2.36), renal failure (OR 5.26, 95% CI 5.07-5.49), and cerebrovascular disease (OR 3.62, 95% CI 3.43-3.82). The median length of hospital stay was four days (IQR, 3-7 days) and the median cost of treatment per admission was US$ 256.63 (IQR, US$ 147.81-531.21). Complications such as acute respiratory failure, acute respiratory distress syndrome (ARDS), septicemia, shock, and acute renal failure made hospital stays two to three days longer and costs three to seven times higher than no complications. CONCLUSION: The mortality from pneumonia among the elderly was high, especially for those over 80 and with multiple medical co-morbidities. PMID- 25123008 TI - The association between bioimpedance analysis and quality of life in pre-dialysis stage 5 chronic kidney disease, hemodialysis and peritoneal dialysis patients. AB - BACKGROUND: Protein-energy wasting is a significant problem in End stage renal disease (ESRD) patients. Furthermore, it compromises the patient's Quality of life (QOL). Multifrequency Bioimpedance Spectroscopy (BIS) is a validated method to assess body composition in dialysis patients. There has been no data on the relationship between body composition and QOL in ESRD patients who were treated with different modalities. OBJECTIVE: To explore the association between body composition as assessed by BIS and QOL in ESRD patients who received different treatment modalities. MATERIAL AND METHOD: The present study is a cross sectional, descriptive analytic study of the association between QOL and BIS in ESRD patients in Burapha University, Chonburi, Thailand. QOL was assessed by WHOQOL-BREF questionnaire, body composition was measured by BIS technique. The difference between groups was tested by one-way ANOVA test, relationship between groups was tested with Pearson correlation test. RESULTS: Eighteen predialysis CKD5, 26 peritoneal dialysis (PD), and 34 hemodialysis (HD) patients were included in the present study. All PD patients had weekly Kt/V > or = 1.7 per week and all HD patients had weekly Kt/V > or = 3.6 per week. There were no statistically difference in baseline characteristics including Charlson comorbidity index, dietary intake, BMI, and blood pressure between groups. Mean QOL scores in each group were in the middle range and not significantly difference. PD patients had more over hydration when compare to HD patients (16.18 +/- 11.24 vs. 2.36 +/- 11.07 %OH/ECW p < 0.0001). There were inversed correlation between overhydration and physical health in HD patients (r = -0.372, p = 0.033) but not in PD and CKD5 patients. CKD5 patients had more lean tissue index (LTI) than PD and HD patients (LTI = 14.34 +/- 3.13, 12.26 +/- 3.65, 11.48 +/- 3.48 kg/m2 respectively, p = 0.023). There were correlation between LTI and overall QOL in CKD5 (r = 0.690, p = 0.002) and PD patients (r = 0.498, p = 0.010). In HD patients, LTI was associated with better physical health (r = 0.464, p = 0.007). CONCLUSION: QOL in predialysis-CKD5, PD and HD patients were not statistically different. HD patients had better volume control than PD patients. Higher LTI were associated with better QOL in ESRD patients. PMID- 25123009 TI - The associations of SEA-alpha thalassemia 1, XmnI-Ggamma polymorphism and beta globin gene mutations with the clinical severity of beta-thalassemia syndrome in northern Thailand. AB - BACKGROUND: At least three genetic factors including beta-thalassemia mutations, alpha-thalassemia, and XmnI-Ggamma polymorphism were shown to modify clinical symptoms in beta-thalassemia disease. OBJECTIVE: To determine associations of beta-thalassemia mutations, SEA-alpha thalassemia 1, and XmnI-Ggamma polymorphism, and clinical severity of beta-thalassemia in northern Thailand. MATERIAL AND METHOD: Thirty-two beta-thalassemia major and 28 beta-thalassemia intermedia attending the Thalassemia Clinic at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand were recruited The beta-globin gene mutations and SEA-alpha thalassemia 1 were determined by MS-PCR and Gap-PCR, respectively. The XmnI-Ggamma polymorphism was identified by RFLP analysis. Odds ratio was calculated to evaluate the associations of these three genetic factors and clinical symptoms. RESULTS: Eight beta-globin gene mutations (both beta0 and beta+) were found Twenty-nine point one percent of the patients had at least one XmnI-Ggamma site (XmnI-Ggamma: +) and 4.1% of the patients were heterozygote for the SEA-alpha thalassemia 1. The beta-globin gene mutations showed maximal impact and the XmnI-Ggamma polymorphism had minimal influence on clinical severity in this cohort. The SEA-alpha thalassemia 1 had the least effect on the clinical severity due to its low prevalence in these patients. CONCLUSION: Although these three genetic factors play roles in modifying clinical symptoms of beta thalassemia, the beta-thalassemia mutations should be considered first, followed respectively by the XmnI-Ggamma polymorphism and the SEA-alpha thalassemia 1, in management and prenatal diagnosis of beta-thalassemia in northern Thailand. PMID- 25123010 TI - Validation of the Thai version of the questionnaire for identifying subjects with potential rheumatic diseases. AB - OBJECTIVE: To translate and evaluate the diagnostic property and the feasibility of the Thai version of the questionnaire for identifying subjects with potential rheumatic diseases. MATERIAL AND METHOD: The original screening questionnaires by Liang MH et al were translated and modified from the English version to the Thai version. The Thai version of the questionnaire was administered to 450 subjects. RESULTS: Two hundred and twenty-five patients who fulfilled standard diagnostic criteria of each rheumatic disease and 225 healthy subjects were consecutively recruited. A positive response to one or more questions of the questionnaire gave a sensitivity (95% confidence interval or CI), specificity (95% CI), positive, and negative likelihood ratios of 94% (90-97), 73% (67-79), 3.48, and 0.08, respectively. The accuracy of test was 93%. Median time-to-complete questionnaire was three minutes (range 0.5-15). Most ofthem (950%) completed questionnaires by themselves. However 12% of the questionnaires had missing items. False positive was prevalent in women, young age, high-educated individuals, and government officers. CONCLUSION: The Thai version of the screening questionnaire is valid and easy to use for identifying subjects with potential rheumatic diseases. It is suitable to use as a screening tool in primary care setting or epidemiologic research. PMID- 25123011 TI - Patency of vascular accesses for Thai hemodialysis patients. AB - OBJECTIVE: Vascular access for hemodialysis is the mode of renal replacement therapy for chronic renal failure patients. The present study reports patency rates of arteriovenous fistula (AVF) and graft (AVG). MATERIAL AND METHOD: Between July 2008 and June 2011, 336 vascular accesses were performed in 293 patients in Department of Surgery, Faculty of Medicine, Khon Kaen University. The patient was follow until June 2012. A retrospective review was conduct to analyze patency rate. RESULTS: Two hundred ninety three patients underwent 286 AVFs and 50 AVGs. Patency rate was analyzed with the Kaplan-Meier method. Primary patency rate of AVF at one, two, and three-year was 78.69%, 70.43%, and 60.72%, respectively Assisted primary patency of AVF at one, two, and three-year was 88.24%, 75.63%, and 40.34%, respectively. Secondary patency rate of AVF at one and two-year was 71.46% and 71.46%, respectively. Primary patency rate of AVG at one, two, and three-year was 63.94%, 43.93%, and 36.60%, respectively. Assisted primary patency of AVG at one-year was 100%. Secondary patency rate of AVG at one year was 46.30%. Graft infection was the major complication ofAVG (12%). CONCLUSION: The authors' results of vascular access surgery were comparable to results from a review of literature. PMID- 25123012 TI - Comparative study of femoral sizing between intraoperative measurement and CT based PSI in total knee arthroplasty. AB - BACKGROUND: Appropriate femoral sizing in total knee arthroplasty (TKA) is an important factor for flexion. An oversized femoral component will decrease flexion gap and postoperative flexion. By using custom cutting blocks technique with computed tomography (CT) imaging to design cutting blocks will help determine sizing of each patient. The differences of femoral sizing between intraoperative measurement and custom cutting blocks technique are still questionable. OBJECTIVE: To compare femoral component sizing between custom cutting blocks technique and conventional technique. MATERIAL AND METHOD: Retrospective cross-sectional study was collected from 2,321 patients underwent primary TKA with the same prosthesis design in Bangkok between January 2012 and December 2012. The population was separated into three groups, group A, 2,053 patients operated by orthopedic surgeons in Bangkok by conventional instrument femoral sizing, group B, 218 patients operated by senior experienced arthroplasty surgeon (Chotanaphuti T) at Phramongkutklao Hospital using the same measurement technique as group A, and group C, 50 patients operated by Chotanaphuti T using custom cutting blocks technique for femoral sizing. The femoral component sizes were assigned from small to large size as number 1 to 6. Chi-square test and Fisher's exact test was used to determine the significant differences between amount of patients of each group. RESULTS: In group A, femoral components were selected in size 1 (n = 157; 8%), 2 (n = 576; 28%), 3 (n = 737; 36%), 4 (n = 431; 21%), 5 (n = 144; 7%), and 6 (n = 8; 0.4%) respectively. In group B, femoral components were selected in size 1 (n = 31; 14%), 2 (n = 55; 25%), 3 (n = 64; 29%), 4 (n = 31; 140%), 5 (n = 37; 180%), and 6 (n = 0; 0%) respectively. In group C, femoral components were selected in size 1 (n = 7; 14%), 2 (n = 19; 38%), 3 (n = 11; 220%), 4 (n = 12; 24%), 5 (n = 1; 20%), and 6 (n = 0; 0%) respectively. The most chosen size of group A and B were No. 3, but for group C was No. 2, which was smaller than the first two group by one size. There were statistical difference in group A versus group B (p < 0.0001), and group B versus group C (p = 0. 009), but not difference in group A versus group C (p = 0. 096). CONCLUSION: Custom cutting blocks technique chooses a femoral component closer to knee anatomy of the patients and smaller than intraoperative technique. There are several possible causes, which include variable of level or sagittal angle error of distal femoral bone cut. PMID- 25123013 TI - The sensory restoration in radial nerve injury using the first branch of dorsal ulnar cutaneous nerve--a cadaveric study for the feasibility of procedure and case demonstration. AB - OBJECTIVE: To demonstrate the new sensory restoration technique in radial nerve injury using the first branch of dorsal ulnar cutaneous nerve as the donor sensory nerve. MATERIAL AND METHOD: Forty formalin-preserved cadavers (18 males and 22 females) were used as the subjects of the present study. The localization of the origin of first branch of dorsal ulnar cutaneous nerve was performed. The measurement was done to determine the origin of this nerve in relation to the tip of ulnar styloid. The simulated transfer was done. The length of the superficial radial nerve that had to be cut was determined. The measurement was done by two observers to determine the reliability of measurement. RESULTS: The mean horizontal distance (X) to the origin of first branch of dorsal ulnar cutaneous nerve measured from the tip of ulnar styloid on the right and left side were 5.22 mm and 6.51 mm respectively. The mean vertical distance (Y) to the origin of first branch of dorsal ulnar cutaneous nerve measured from the tip of ulnar styloid on the right and left side were -7.72 mm and -4.37 mm respectively. The mean length of superficial radial nerve that had to be cut to allow tension free anastomosis, measured from the tip of radial styloid on the right and left side were 68.21 mm and 65.92 mm respectively. The estimated average size of the transferred branch of ulnar cutaneous nerve was about 70% of the size of superficial radial nerve. CONCLUSION: The sensory restoration in radial nerve injury using sensory nerve transfer from the first branch of dorsal ulnar cutaneous nerve was technically feasible regarding to the comparable size between two nerves and anatomic consistency of the first branch of dorsal ulnar cutaneous nerve. PMID- 25123014 TI - CT perfusion in predicting treatment response of nasopharyngeal carcinoma. AB - BACKGROUND: Direct nasopharyngoscope with biopsy is the gold standard for assessing tumor response of nasopharyngeal carcinoma (NPC). It is invasive with risk of hemorrhage or infection. OBJECTIVE: Explore the usefulness of pre treatment CTperfusion (CTP) and clarify the parameters in predicting the treatment response. MATERIAL AND METHOD: Twelve patients with histologically proven NPC who underwent pretreatment contrast enhanced CT (CECT) and CTP with parameters (blood flow (BF), blood volume (BV) and permeability), followed by CECT at three months after complete concurrent chemo-radiotherapy or radiotherapy were included in this prospective, cross-sectional study. Pre- and post-treatment primary tumor volumes based on free hand drawn region encompassing the entire primary tumor were measured and compared The response to therapy was also assessed by RECIST guideline version 1.1, based on sum of the diameters of longest diameter for primary tumor and minimal transverse diameter for nodal lesions for all target lesions on the pre- and post-treatment imaging, and classified into "Non-response" group and "Complete response" group. Statistical analysis was performed using Pearson 's correlation coefficients and Mann-Whitney U test. RESULTS: Ten and two patients (83.3%, 16.7%) belonged to "Complete response" and "Non-response "groups respectively. Elevated permeability, BF and BV had a following trend of positive correlation with degree of primary tumor volume reduction without statistical significance. The values ofpermeability, BFE and BV had a trend to be higher in "Complete response" group compared with "Non response" group (p = 0.053, 0.390 and 0.519 respectively). The permeability had the highest predictive value with an area under the ROC curve of 0.95 and cutoff value of 45 ml/100 g/min (sensitivity, 100%; specificity, 90%). CONCLUSION: Pre treatment CTP can be useful non-invasive tool in predicting treatment response of NPC. Permeability is the excellent parameter used to differentiate between complete and non-response groups. PMID- 25123015 TI - Efficiency comparison of three methods for extracting genomic DNA of the pathogenic oomycete Pythium insidiosum. AB - BACKGROUND: The fungus-like organism Pythium insidiosum is the causative agent of a life-threatening tropical infectious disease, pythiosis, which has high rates of morbidity and mortality. A lack of reliable diagnostic tools and effective treatments for pythiosis presents a major challenge to healthcare professionals. Unfortunately, surgical removal of infected organs remains the default treatment for pythiosis. P. insidiosum is an understudied organism. In-depth study of the pathogen at the molecular level could lead to better means of infection control High quality genomic DNA (gDNA) is needed for molecular biology-based research and application development, such as: PCR-assisted diagnosis, population studies, phylogenetic analysis, and molecular genetics assays. OBJECTIVE: To evaluate quality and quantity of the P. insidiosum gDNA extracted by three separate protocols intended for fungal gDNA preparation. MATERIAL AND METHOD: Seven P. insidiosum isolates were subjected to gDNA extraction by using conventional extraction, rapid-extraction, and salt-extraction protocols. RESULTS: The conventional protocol offered the best gDNA in terms of quality and quantity, and could be scaled up. The rapid-extraction protocol had a short turnaround time, but the quality and quantity of the gDNA obtained were limited. The salt extraction protocol was simple, rapid, and efficient, making it appealing for high throughput preparation of small-scale gDNA samples. CONCLUSION: Compared to rapid-extraction protocol, both conventional-extraction and salt-extraction protocols provided a better quality and quantity of gDNA, suitable for molecular studies of P. insidiosum. In contrast to the other two methods, the salt extraction protocol does not require the use of hazardous and expensive materials such as phenol, chloroform, or liquid nitrogen. PMID- 25123016 TI - Effectiveness of olanzapine for the treatment of breakthrough chemotherapy induced nausea and vomiting. AB - OBJECTIVE: To evaluate safety and efficacy of olanzapine for breakthrough emesis in addition to standard antiemetic regimen in cancer patients receiving highly emetogenic chemotherapy. MATERIAL AND METHOD: A phase II prospective open label clinical trial was conducted in tertiary care based hospital. Forty-six cancer patients diagnosed with solid tumors were enrolled to receive at least one cycle of highly emetogenic chemotherapy (HEC) every two to four weeks. Each patient was provided standard antiemetic consisting of the generic form of ondansetron plus corticosteroids and metoclopramide according to clinical practice guideline. Olanzapine was administered as 5 mg orally every 12 hours for two doses in patients experiencing breakthrough emesis for at least one episode despite standard prevention. The efficacy and tolerability were evaluated every six hours for 24 hours (utilizing Index of Nausea, Vomiting and Retching: INVR tool). RESULTS: Of 46 evaluable patients receiving HEC and additional olanzapine between September 2009 and July 2010, the complete response of breakthrough emesis, retching, and nausea control among patients were 60.9%, 71.7%, and 50.0%, respectively. Adverse events reported were mild and tolerable including dizziness, fatigue, and dyspepsia. CONCLUSION: Olanzapine is considered to be safe and effective treatment of breakthrough vomiting in cancer patients undergoing highly emetogenic chemotherapy in the present study. PMID- 25123017 TI - Co-existence of porokeratosis variants concurrent with Bowen's disease: two rare cases report. AB - Coexisting variants of porokeratosis rarely occurs. Disseminated superficial porokeratosis (DSP) is characterized by multiple uniform small annular papules distributed all over body. DSP commonly coexist with linear porokeratosis (LP), but it is uncommon for DSP to coexist with porokeratosis of Mibelli (PM). PM presents with central atrophic erythematous plaques and thread-like elevated border. It occurs mainly on extremities. Although malignant transformation can be found in the porokeratosis, there is still no report case of coexisting variants of porokeratosis concurrent with Bowen's disease. The clinical and histopathologic finding of rare coexisting variants of porokeratosis (PM and DSP) concurrent with squamous dysplasia is described. PMID- 25123019 TI - Itching for answers: how histamine relaxes lymphatic vessels. AB - In the current issue of Microcirculation, studies by Kurtz et al. and Nizamutdinova et al. together provide new evidence supporting a role for histamine as an endothelial-derived molecule that inhibits lymphatic muscle contraction. In particular, Nizamutdinova et al. show that the effects of flow induced shear stress on lymphatic endothelium are mediated by both nitric oxide and histamine, since only blockade of both prevents contraction strength and frequency from being altered by flow. Separately, Kurtz et al. used confocal microscopy to determine a preferential expression of histamine receptors on the lymphatic endothelium and demonstrated that histamine applied to spontaneously contracting collecting lymphatics inhibits contractions. Previous studies disagreed on whether histamine stimulates or inhibits lymphatic contractions, but also used differing concentrations, species, and preparations. Together these new reports shed light on how histamine acts within the lymphatic vasculature, but also raise important questions about the cell type on which histamine exerts its effects and the signaling pathways involved. This editorial briefly discusses the contribution of each study and its relevance to lymphatic biology. PMID- 25123020 TI - Call for papers: development of action mirroring: submissions due 1 February 2015. PMID- 25123021 TI - Is increased choroidal thickness associated with primary angle closure? PMID- 25123018 TI - Chronic loss of noradrenergic tone produces beta-arrestin2-mediated cocaine hypersensitivity and alters cellular D2 responses in the nucleus accumbens. AB - Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. Chronic inhibition of dopamine beta-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in beta arrestin2 (betaArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of betaArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Galphai inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Galphas inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in betaArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs. PMID- 25123023 TI - Fumarates, a new treatment option for therapy-resistant hidradenitis suppurativa: a prospective open-label pilot study. PMID- 25123022 TI - Targets for parathyroid hormone in secondary hyperparathyroidism: is a "one-size fits-all" approach appropriate? A prospective incident cohort study. AB - BACKGROUND: Recommendations for secondary hyperparathyroidism (SHPT) consider that a "one-size-fits-all" target enables efficacy of care. In routine clinical practice, SHPT continues to pose diagnosis and treatment challenges. One hypothesis that could explain these difficulties is that dialysis population with SHPT is not homogeneous. METHODS: EPHEYL is a prospective, multicenter, pharmacoepidemiological study including chronic dialysis patients (>= 3 months) with newly SHPT diagnosis, i.e. parathyroid hormone (PTH) >= 500 ng/L for the first time, or initiation of cinacalcet, or parathyroidectomy. Multiple correspondence analysis and ascendant hierarchical clustering on clinico biological (symptoms, PTH, plasma phosphorus and alkaline phosphatase) and treatment of SHPT (cinacalcet, vitamin D, calcium, or calcium-free calcic phosphate binder) were performed to identify distinct phenotypes. RESULTS: 305 patients (261 with incident PTH >= 500 ng/L; 44 with cinacalcet initiation) were included. Their mean age was 67 +/- 15 years, and 60% were men, 92% on hemodialysis and 8% on peritoneal dialysis. Four subgroups of SHPT patients were identified: 1/ "intermediate" phenotype with hyperphosphatemia without hypocalcemia (n = 113); 2/ younger patients with severe comorbidities, hyperphosphatemia and hypocalcemia, despite SHPT multiple medical treatments, suggesting poor adherence (n = 73); 3/ elderly patients with few cardiovascular comorbidities, controlled phospho-calcium balance, higher PTH, and few treatments (n = 75); 4/ patients who initiated cinacalcet (n = 43). The quality criterion of the model had a cut-off of 14 (>2), suggesting a relevant classification. CONCLUSION: In real life, dialysis patients with newly diagnosed SHPT constitute a very heterogeneous population. A "one-size-fits-all" target approach is probably not appropriate. Therapeutic management needs to be adjusted to the 4 different phenotypes. PMID- 25123024 TI - Continuous and simultaneous estimation of finger kinematics using inputs from an EMG-to-muscle activation model. AB - BACKGROUND: Surface electromyography (EMG) signals are often used in many robot and rehabilitation applications because these reflect motor intentions of users very well. However, very few studies have focused on the accurate and proportional control of the human hand using EMG signals. Many have focused on discrete gesture classification and some have encountered inherent problems such as electro-mechanical delays (EMD). Here, we present a new method for estimating simultaneous and multiple finger kinematics from multi-channel surface EMG signals. METHOD: In this study, surface EMG signals from the forearm and finger kinematic data were extracted from ten able-bodied subjects while they were tasked to do individual and simultaneous multiple finger flexion and extension movements in free space. Instead of using traditional time-domain features of EMG, an EMG-to-Muscle Activation model that parameterizes EMD was used and shown to give better estimation performance. A fast feed forward artificial neural network (ANN) and a nonparametric Gaussian Process (GP) regressor were both used and evaluated to estimate complex finger kinematics, with the latter rarely used in the other related literature. RESULTS: The estimation accuracies, in terms of mean correlation coefficient, were 0.85 +/- 0.07, 0.78 +/- 0.06 and 0.73 +/- 0.04 for the metacarpophalangeal (MCP), proximal interphalangeal (PIP) and the distal interphalangeal (DIP) finger joint DOFs, respectively. The mean root-mean-square error in each individual DOF ranged from 5 to 15%. We show that estimation improved using the proposed muscle activation inputs compared to other features, and that using GP regression gave better estimation results when using fewer training samples. CONCLUSION: The proposed method provides a viable means of capturing the general trend of finger movements and shows a good way of estimating finger joint kinematics using a muscle activation model that parameterizes EMD. The results from this study demonstrates a potential control strategy based on EMG that can be applied for simultaneous and continuous control of multiple DOF(s) devices such as robotic hand/finger prostheses or exoskeletons. PMID- 25123026 TI - Could monitoring methylation markers aid the management of schizophrenia? PMID- 25123025 TI - Biomarker and more: can translocator protein 18 kDa predict recovery from brain injury and myocarditis? PMID- 25123029 TI - Biomarkers and aging. AB - Biomarkers and Ageing 25 February 2014, London, UK This conference was organized by Euroscicon and was part of the 2014 Ageing Summit. The central theme was biomarkers and aging including current research on biomarkers at the genomics and proteomics level. The informal atmosphere of the conference promoted interaction and networking opportunities between key leaders from industry, academic and clinics. Presentations as well as the discussion panel session brought opportunities to widely discuss the relevance of biomarkers as signatures for human aging or age-related diseases. The meeting highlighted the importance of genomics and regulatory elements in aging, their probable role in successful aging and their potential interest for future antiaging approaches. The meeting was chaired by David Melzer and Lorna Harries (University of Exeter, UK). PMID- 25123030 TI - Development of NuQ nucleosome blood tests for the detection of colon cancer. AB - Dr Jake Micallef speaks to Hannah L Wilson, Commissioning Editor: Dr Micallef has 20 years of experience in research and development and in the management of early stage biotechnical companies, including the manufacture of biotechnology products and the establishment of manufacturing operations. Dr Micallef gained this experience while working for WHO over a 10-year period from 1985. While working for WHO, Dr Micallef developed new diagnostic products in the areas of reproductive health and cancer. In 1990 he commenced development of a new diagnostic technology platform for WHO that was launched in 1992 and supported 13 tests. Dr Micallef also initiated and implemented in-house manufacture (previously outsourced to Abbott Diagnostics Inc., Dartford, UK) and worldwide distribution of these products for WHO. In 1990, he started a 'not-for-profit' WHO company, Immunometrics Ltd (London, UK), which marketed and distributed those diagnostic products worldwide. In 1999 Dr Micallef studied for an MBA and went on to co-found Gene Expression Technologies Ltd (London, UK) in 2001 where he successfully lead the development of the chemistry of the GeneICE technology and implemented the manufacture of GeneICE molecules. He also played a major role in business development and procured a GeneICE contract with Bayer Pharmaceuticals (Leverkusen, Germany). From 2004 to 2007, he taught 'science and enterprise' to science research workers from four universities at CASS Business School (London, UK) before joining Cronos Therapeutics (London, UK) in 2004. In 2006 Cronos was listed in the UK on AIM, becoming ValiRx. Dr Micallef continued to work as Technical Officer for ValiRx, where he in-licensed the Hypergenomics and Nucleosomics technologies and co-founded ValiBio SA (Namur, Belgium), which is now Belgian Volition SA, a subsidiary of Singapore Volition. Dr Micallef was educated at King's College London (UK; BSc, Biology and Chemistry, 1977; PhD Physical Chemistry, 1981), St Thomas' Hospital Medical School, London (UK; MSc Chemical Pathology, 1985) and Imperial College Management School (UK; MBA, 2000). PMID- 25123031 TI - Dynamic sequencing of circulating tumor DNA: novel noninvasive cancer biomarker. PMID- 25123032 TI - Pilot study of A-FABP levels as a predictive factor of SPECT results in asymptomatic relatives of patients with cardiovascular disease. AB - BACKGROUND: A-FABP is a promising link between metabolic syndrome and atherosclerosis. It is not well known whether level of A-FABP predicts results of SPECT. PATIENTS & METHODS: In 82 subjects (53 males) with a median age of 54 years, who were first-degree relatives of patients with cardiovascular disease, the following tests and examinations were performed: A-FABP, calcium score (CS) and SPECT. RESULTS: Subjects with positive and negative SPECT results differed significantly in the noncategorized CS (p = 0.001), uric acid (p = 0.025) and the total cholesterol:high-density lipoprotein ratio (p = 0.043), but not in other parameters (including A-FABP). To predict SPECT results, the best model proved to be a logistic regression model with gender and noncategorized CS as predictors, with an area under the receiver operating characteristic curve of 0.89 (the sensitivity and specificity based on a CS cutoff of 11.1 were 77.78 and 75.34%, respectively). CONCLUSION: The serum level of A-FABP is not a predictor of a positive SPECT result. PMID- 25123034 TI - Circulating microparticles reflect treatment effects and clinical status in multiple sclerosis. AB - AIM: To evaluate whether circulating microparticles (MPs) derived from three cell subtypes (platelets, total leukocytes or monocytes) obtained from multiple sclerosis (MS) patients were modulated depending on the clinical status and to investigate the effect of treatments on MP levels. PATIENTS & METHODS: The MP counts were assessed with flow cytometry. RESULTS: The platelet-derived MP level was higher in untreated MS patients than controls. Relapsing-remitting patients showed the highest levels in the three subtypes of MP while secondary progressive patients presented similar levels to those of healthy controls. Treatments had significant effects increasing the three subtypes of MP counts. CONCLUSION: We suggest that MPs play a role in MS pathogenesis, reflecting disease status with an increment of their shedding during inflammatory periods and turning to baseline during chronic progressive degeneration. PMID- 25123033 TI - Sialylation of Thomsen-Friedenreich antigen is a noninvasive blood-based biomarker for GNE myopathy. AB - AIM: The exact pathomechanism of GNE myopathy remains elusive, but likely involves aberrant sialylation. We explored sialylation status of blood-based glycans as potential disease markers. METHODS: We employed immunoblotting, lectin histochemistry and mass spectrometry. RESULTS: GNE myopathy muscle showed hyposialylation of predominantly O-linked glycans. The O-linked glycome of patients' plasma compared with controls showed increased amounts of desialylated Thomsen-Friedenreich (T)-antigen, and/or decreased amounts of its sialylated form, ST-antigen. Importantly, all patients had increased T/ST ratios compared with controls. These ratios were normalized in a patient treated with intravenous immunoglobulins as a source of sialic acid. DISCUSSION: GNE myopathy clinical trial data will reveal whether T/ST ratios correlate to muscle function. CONCLUSION: Plasma T/ST ratios are a robust blood-based biomarker for GNE myopathy, and may also help explain the pathology and course of the disease. PMID- 25123035 TI - Serum HER2 extracellular domain as a potential alternative for tissue HER2 status in metastatic gastric cancer patients. AB - AIM: We investigated whether serum concentrations of the HER2 extracellular domain (ECD) can be used as an alternative to test tissue HER2 status in metastatic gastric cancer. MATERIALS & METHODS: A total of 133 cases of metastatic gastric cancer were included in present study. Serum HER2 ECD was measured by chemiluminescence immunoassay (CLIA). Receiver operating characteristic curve analysis was used to determine optimal serum HER2 ECD concentrations for differentiation between positive and negative HER2 status. RESULTS: The median level of serum HER2 ECD was 9.6 ng/ml in metastatic gastric cancer patients. There was a significant relationship between serum and tissue levels of HER2 protein (p < 0.001). Area under the curve for serum HER2 ECD was 0.771 (95% CI: 0.682-0.860). CONCLUSION: Levels of serum HER2 ECD are highly correlated with tissue HER2 status in metastatic gastric cancer. Serum HER2 ECD assay can be considered as a potential alternative for tissue HER2 status. PMID- 25123036 TI - KLK11 mRNA expression predicts poor disease-free and overall survival in colorectal adenocarcinoma patients. AB - BACKGROUND: Dysregulated expression of several KLK family members has been observed in colorectal adenocarcinoma. In the present study, the prognostic value of KLK11 mRNA expression as a molecular tissue biomarker in colorectal adenocarcinoma was examined. MATERIALS & METHODS: Using quantitative real-time PCR, KLK11 mRNA expression was studied in 120 cancerous and 41 paired noncancerous colorectal specimens obtained from 120 patients with primary colorectal adenocarcinoma. RESULTS: A significant upregulation of KLK11 transcripts in colorectal tumors was observed. KLK11 mRNA expression was associated with the depth of tumor invasion and the histological grade. Furthermore, KLK11 mRNA expression predicted poor disease-free and overall survival, independently of patient gender, age, tumor size, location, histological subtype, grade, venous invasion, lymphatic invasion, TNM stage, radiotherapy and chemotherapy treatment. CONCLUSION: KLK11 mRNA expression could be considered as a new molecular prognostic biomarker in colorectal adenocarcinoma, with additional prognostic value in patients with highly invasive tumors and/or positive lymph nodes. PMID- 25123037 TI - IGFBP1 in epithelial circulating tumor cells as a potential response marker to selective internal radiation therapy in hepatocellular carcinoma. AB - BACKGROUND: Local ablative techniques such as selective internal radiation therapy (SIRT) have become the mainstay of treating hepatocellular carcinoma (HCC) in the bridging-to-transplant and palliative setting. We recently demonstrated that epithelial circulating tumor cells (CTCs) correlate to an unfavorable outcome. We wanted to scrutinize whether molecular markers detected in this specific CTC subgroup may also have clinical implications. MATERIALS & METHODS: Mononuclear cells and CTCs were isolated from peripheral blood samples using density gradient centrifugation followed by depletion of hematopoietic and enrichment of epithelial (EpCAM(+)) cells employing immunomagnetic beads. The mRNA expression of candidate markers was correlated with response to SIRT in 25 patients using quantitative real-time reverse-transcription PCR. RESULTS: IGFBP1 mRNA expression levels were significantly correlated with time to progression in a Kaplan-Meier log rank test (p = 0.04; 0 vs 4 months) and receiver operating characteristic analysis demonstrated a potential use to predict patients with shortened time to progression (area under the curve: 0.8; 95% CI: 0.44-0.98; p = 0.03). CONCLUSION: The EpCAM fraction of CTCs may be useful to detect novel molecular markers to individualize treatment decision in patients with HCC. PMID- 25123038 TI - Novel single-chain antibody GD3A10 defines a chondroitin sulfate biomarker for ovarian cancer. AB - AIMS: Ovarian cancer has the highest case-to-fatality-index of all gynecological cancers. In this study, tumor-related alterations in the extracellular matrix, especially regarding chondroitin sulfate glycosaminoglycans, are proposed as a novel biomarker in ovarian cancer. MATERIALS & METHODS: Phage display technology was applied to select antibody GD3A10, which was obtained by biopanning using embryonic glycosaminoglycans as a source for carcinogenic antigens. GD3A10 antigen specificity was studied in situ using glycosaminoglycan degrading enzymes. A patient cohort (n = 159) was immunohistochemically stained. Scoring was correlated with clinical prognostic parameters and survival. Normal rat organs were used to study normal antigen distribution. RESULTS: GD3A10 is a specific anti-chondroitin sulfate antibody and the epitope was absent or very restricted in normal rat organs, normal ovaries and benign ovarian tumors. Strong stromal expression was observed in malignant ovarian tumors, and correlated with poor prognostic factors such as subtype, tumor grade and recurrence. CONCLUSION: tumor-associated glycosaminoglycans are an interesting source of biomarkers in ovarian cancer, as shown here using chondroitin sulfate antibody GD3A10. PMID- 25123039 TI - Biomarkers of cartilage and surrounding joint tissue. AB - The identification and clinical demonstration of efficacy and safety of osteo- and chondro-protective drugs are met with certain difficulties. During the last few decades, the pharmaceutical industry has, in the field of rheumatology, experienced disappointments associated with the development of disease modification. Today, the vast amount of patients suffering from serious, chronic joint diseases can only be offered treatments aimed at improving symptoms, such as pain and acute inflammation, and are not aimed at protecting the joint tissue. This huge, unmet medical need has been the driver behind the development of improved analytical techniques allowing better and more efficient clinical trial design, implementation and analysis. With this review, we aim to provide a brief and general overview of biochemical markers of joint tissue, with special focus on neoepitopes. Furthermore, we highlight recent studies applying biochemical markers in joint degenerative diseases. These disorders, including osteoarthritis, rheumatoid arthritis and spondyloarthropathies, are the most predominant disorders in Europe and the USA, and have enormous socioeconomical impact. PMID- 25123040 TI - miRNA panels as biomarkers for bladder cancer. AB - AIM: Specific miRNA profiles have been identified for several samples from patients with bladder cancer. The results are not always congruent and partly contradictory. A comparison of published data was performed to select potential markers. MATERIALS & METHODS: A literature search in PubMed identified 79 articles published prior to June 2013. Reports regarding the detection of miRNAs in urine and blood have rarely been published; to date, nine respectively three articles are available. RESULTS: The comparison of published data proved the utility of miRNAs as diagnostic and prognostic indicators of bladder cancer. In urine samples from bladder cancer patients, seven miRNAs were concordantly expressed with tumor tissues. CONCLUSION: Standardization is strictly required in pre-analytics and methods of miRNA measurements. PMID- 25123041 TI - Implementation of PSA-based active surveillance in prostate cancer. AB - Prostate cancer screening had led to the diagnosis of a large proportion of localized and low-risk disease. Many of these cancer cases are believed to be indolent and would not be clinically perceived in the absence of screening. In addition to that, the wide use of active treatment has exposed these patients to treatment-related quality-of-life impact. In this setting active surveillance as a way of deferring active treatment and reserving such treatment to cases of disease progression only has gained interest. PSA has been widely used to identify patients eligible for active surveillance and also for disease monitoring. The goal of this review was to describe the place of PSA in the monitoring of patients under active surveillance based on the existing studies and to discuss the importance of PSA in light of other existing or emerging tools to monitor prostate cancer in active surveillance. PMID- 25123042 TI - Detection of colorectal cancer by DNA methylation biomarker SEPT9: past, present and future. AB - Colorectal cancer has become the third most common cancer in the world. Early diagnosis and treatment can significantly reduce colorectal cancer mortality. The current routinely used fecal-based screening methods do not provide satisfactory sensitivity. Although colonoscopy provides macroscopic diagnosis, the compliance is low due to its inconvenience and complications. Hence, the development of new screening methods is needed urgently. Peripheral blood SEPT9 gene methylation assay has become a potential option with promising future for early detection and screening of colorectal cancer. It is shown to be convenient, reliable with good compliance by several clinical trials. This article will review the theoretical foundation and development of the assay, focusing on its clinical trials, comparing it with other screening methods and discussing its future applications. PMID- 25123045 TI - Scratch wound closure of myoblasts and myotubes is reduced by inflammatory mediators. AB - Complex interactions exist between muscle repair processes and acute inflammatory responses that are initiated by exercise-induced muscle damage. The purpose of this study was to examine whether inflammatory mediators secreted by activated macrophages affect the migration of myogenic cells to the injury site. Migration was measured using a scratch wound closure assay in C2 C12 -derived myogenic cells incubated in activated macrophage-conditioned medium. Both myoblast and myotube migrations were significantly reduced in activated macrophage-conditioned medium compared with control medium. Furthermore, we demonstrated that the inhibitory effect on myoblast and myotube migrations was mediated, at least in part, by the two major cytokines secreted by activated macrophages, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6. These findings suggest that the migration rate of myogenic cells may be reduced by inflammatory mediators. It may provide useful insights for future researches on the role of macrophages in the process of muscle repair and regeneration. PMID- 25123046 TI - Multicomponent reactions involving phosphines, arynes and aldehydes. AB - Although nucleophilic phosphine-catalysis is a powerful tool for the construction of various carbocycles and heterocycles, the reactions in which phosphines are incorporated into the final product are rare, and the reports on phosphine addition to highly electrophilic arynes are scarce. Herein, we report the phosphine triggered multicomponent reaction of arynes and aldehydes, which takes place via the formal [3+2] cycloaddition of an initially generated 1,3 phosphonium zwitterion from phosphines and arynes with aldehydes. The reaction resulted in the formation of a diverse range of stable pentacovalent phosphoranes in good yields based on the benzooxaphosphole system. PMID- 25123044 TI - Effect of Part D coverage restrictions for antidepressants, antipsychotics, and cholinesterase inhibitors on related nursing home resident outcomes. AB - OBJECTIVES: In 2006, Medicare Part D transitioned prescription drug coverage for dual-eligible nursing home residents from Medicaid to Medicare and randomly assigned them to Part D prescription drug plans (PDPs). Because PDPs may differ in coverage, plans may be more or less generous for drugs that an individual is taking. Taking advantage of the fact that randomization mitigates potential selection bias common in observational studies, this study sought to assess the effect of PDP coverage on resident outcomes for three medication classes- antidepressants, antipsychotics, and cholinesterase inhibitors. DESIGN: Retrospective cohort study to examine the effect of coverage restrictions- including noncoverage and coverage with restrictions--on depression, hallucinations and delusions, aggressive behaviors, cognitive performance, and activities of daily living for dual-eligible nursing home residents randomized to PDPs in 2006 to 2008. The analyses further adjusted for baseline health status to address any residual imbalances in the comparison groups. SETTING: Linked data from Medicare claims, Minimum Data Set assessments, pharmacy claims, and PDP formulary information. PARTICIPANTS: Dual-eligible nursing home residents aged 65 and older living in facilities that contracted with a single pharmacy provider. RESULTS: PDP coverage restrictions in three medication classes of interest were not significantly associated with the resident outcomes examined. Although cholinesterase inhibitor users facing coverage restrictions had a 0.04-point lower depression rating score than residents facing no restrictions, this difference was not statistically significant after adjusting for multiple comparisons. CONCLUSION: The findings suggest that exogenous changes in coverage for three commonly used medication classes had no detectable effect on nursing home resident outcomes in 2006 to 2008. There are several possible explanations for this lack of association, including the role of policy protections for dual eligible nursing home residents and the possibility that suitable clinical alternatives were identified or that previously used medications offered little clinical benefit. PMID- 25123047 TI - Poor adherence to the World Health Organization guidelines of treatment of severe pneumonia in children at Khartoum, Sudan. AB - BACKGROUND: Community-acquired pneumonia (CAP) is as a major cause for childhood morbidity and mortality worldwide. This study was conducted to investigate the adherence and response of the WHO guidelines for treatment of severe pneumonia. METHOD: A cross-sectional study was conducted in the period of June 2009 to July 2010 at Khartoum Hospital, Sudan. Children admitted and treated for severe pneumonia were enrolled. RESULTS: Only 39 (18.8%) out of 208 enrolled children received prescriptions that were adherent to the WHO guidelines of treatment of severe pneumonia. In logistic regression none of the investigated variable (age, gender, and clinical presentations) was associated with the adherence to the WHO guidelines. There was no significant difference in the response between adherent and non-adherent prescriptions. There was no association between the demographic, clinical data, treatment-adherence to the guidelines and the patients' response. CONCLUSION: There is a poor (18.8%) adherence to the WHO guidelines of the treatment of severe pneumonia in the region regardless to the age, gender and clinical presentation. PMID- 25123048 TI - Quality assessment of 3D-CTVR, MPR and section plane techniques in ossicular chain reconstruction in middle ear cholesteatoma. AB - AIM: To assess the quality of three-dimensional volume rendered computer tomography (3D-CTVR), multi-planar reformation (MPR) and CT section plane in the fine diagnosis of ossicular chain in middle ear cholesteatoma. METHODS: Sixty patients with middle ear cholesteatoma were selected in this retrospective study. All cases underwent pre-operative CT scan. The respective radiologic reports of the ossicles status via three protocols were then compared to surgical findings. RESULTS: Quality assessment of these three protocols in the fine diagnosis of fine ossicles buried inside the soft tissue showed that both CTVR and MPR are more superior to conventional section plane, especially CTVR. CONCLUSION: The uses of CTVR and MPR, in conjunction with conventional section plane, are better able to show where the true and fine ossicular chain in the cholesteatoma mass is. In the final analysis, we believe that the use of CTVR and MPR techniques can have profound contributive value in future clinical work. PMID- 25123050 TI - Bovine tuberculosis slaughter surveillance in the United States 2001-2010: assessment of its traceback investigation function. AB - BACKGROUND: The success of tracing cattle to the herd of origin after the detection and confirmation of bovine tuberculosis (TB) lesions in cattle at slaughter is a critical component of the national bovine TB eradication program in the United States (U.S.). The aims of this study were to 1) quantify the number of bovine TB cases identified at slaughter that were successfully traced to their herd of origin in the U.S. during 2001-2010, 2) quantify the number of successful traceback investigations that found additional TB infected animals in the herd of origin or epidemiologically linked herds, and 3) describe the forms of animal identification present on domestic bovine TB cases and their association with traceback success. RESULTS: We analyzed 2001-2010 data in which 371 granulomatous lesions were confirmed as bovine TB. From these 114 bovine TB cases, 78 adults (i.e. sexually intact bovines greater than two years of age), and 36 fed (i.e. less than or equal to two years of age) were classified as domestic cattle (U.S. originated). Of these adults and fed cases, 83% and 13% were successfully traced, respectively. Of these traceback investigations, 70% of adult cases and 50% of fed cases identified additional bovine TB infected animals in the herd of origin or an epidemiologically linked herd. We found that the presence of various forms of animal identification on domestic bovine TB cases at slaughter may facilitate successful traceback investigations; however, they do not guarantee it. CONCLUSIONS: These results provide valuable information with regard to epidemiological traceback investigations and serve as a baseline to aid U.S. officials when assessing the impact of newly implemented strategies as part of the national bovine TB eradication in the U.S. PMID- 25123051 TI - Comparison of three noninvasive methods for hemoglobin screening of blood donors. AB - BACKGROUND: To prevent phlebotomy of anemic individuals and to ensure hemoglobin (Hb) content of the blood units, Hb screening of blood donors before donation is essential. Hb values are mostly evaluated by measurement of capillary blood obtained from fingerstick. Rapid noninvasive methods have recently become available and may be preferred by donors and staff. The aim of this study was to evaluate for the first time all different noninvasive methods for Hb screening. STUDY DESIGN AND METHODS: Blood donors were screened for Hb levels in three different trials using three different noninvasive methods (Haemospect [MBR Optical Systems GmbH & Co. KG], NBM 200 [LMB Technology GmbH], Pronto-7 [Masimo Europe Ltd]) in comparison to the established fingerstick method (CompoLab Hb [Fresenius Kabi GmbH]) and to levels obtained from venous samples on a cell counter (Sysmex [Sysmex Europe GmbH]) as reference. The usability of the noninvasive methods was assessed with an especially developed survey. RESULTS: Technical failures occurred by using the Pronto-7 due to nail polish, skin color, or ambient light. The NBM 200 also showed a high sensitivity to ambient light and noticeably lower Hb levels for women than obtained from the Sysmex. The statistical analysis showed the following bias and standard deviation of differences of all methods in comparison to the venous results: Haemospect, -0.22 +/- 1.24; NBM, 200 -0.12 +/- 1.14; Pronto-7, -0.50 +/- 0.99; and CompoLab Hb, 0.53 +/- 0.81. CONCLUSION: Noninvasive Hb tests represent an attractive alternative by eliminating pain and reducing risks of blood contamination. The main problem for generating reliable results seems to be preanalytical variability in sampling. Despite the sensitivity to environmental stress, all methods are suitable for Hb measurement. PMID- 25123052 TI - Low physiological levels of prostaglandins E2 and F2alpha improve human sperm functions. AB - Prostaglandins (PGs) have been reported to be present in the seminal fluid and cervical mucus, affecting different stages of sperm maturation from spermatogenesis to the acrosome reaction. This study assessed the effects of low physiological PGE2 and PGF2alpha concentrations on human sperm motility and on the ability of the spermatozoa to bind to the zona pellucida (ZP). Human spermatozoa were isolated from seminal samples with normal concentration and motility parameters and incubated with 1MUM PGE2, 1MUM PGF2alpha or control solution to determine sperm motility and the ability to bind to human ZP. The effects of both PGs on intracellular calcium levels were determined. Incubation for 2 or 18h with PGE2 or PGF2alpha resulted in a significant (P<0.05) increase in the percentage of spermatozoa with progressive motility. In contrast with PGF2alpha, PGE2 alone induced an increase in sperm intracellular calcium levels; however, the percentage of sperm bound to the human ZP was doubled for both PGs. These results indicate that incubation of human spermatozoa with low physiological levels of PGE2 or PGF2alpha increases sperm functions and could improve conditions for assisted reproduction protocols. PMID- 25123053 TI - Pre-existing anti-HLA antibodies negatively impact survival of pediatric aplastic anemia patients undergoing HSCT. AB - Graft failure and survival are the major problems for patients with aplastic anemia undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti-HLA antibodies negatively impact engraftment in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic HSCT at a single institution between 2006 and 2012 investigated the influence of anti-HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti-HLA antibodies. Pre-existing anti-HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti-HLA class I antibodies. Anti-HLA antibodies were associated with worse five-yr survival (78.6% vs. 100%, p = 0.021) and higher treatment-related mortality (21.4% vs. 0%, p = 0.028) compared with antibody-negative patients. Anti-HLA class I antibody-positive patients had poorer five-yr survival (75.0%) than anti-HLA class I&II antibody-positive and antibody-negative patients (87.5% and 100.0%, respectively, p = 0.039). Presence of anti-HLA class I antibodies (p = 0.024) and older age (10 yr or more; p = 0.027) significantly increased the risk of post-HSCT mortality. Pre-existing anti HLA antibodies negatively affect the outcome of HSCT in pediatric patients with aplastic anemia. Routine testing for anti-HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT. PMID- 25123054 TI - Tobacco use and smoking cessation among third-year dental students in southern Brazil. AB - The aim of the present cross-sectional study was to assess tobacco use and smoking cessation among third-year dental students in southern Brazil. The Global Health Professions Student Survey questionnaire was used in eight dental schools in Rio Grande do Sul state, Brazil. Of the 663 eligible students, 576 (87%) participated. The prevalence of current smoking was 19.1% [95% confidence interval (CI): 12.9-25.3%], and 61.6% (95% CI: 54.9-68.3%) of students reported having smoked at least once in their lifetime. The prevalence of dental students who had smoked >= 100 cigarettes in their lifetime was 17.1% (95% CI: 12.5 21.7%). Being frequently exposed to other smokers at home or in other places (second-hand smoke) increased the likelihood of current smoking by two- to threefold. Approximately 6.1% (95% CI: 3.5-8.7%) of the students reported that they currently wanted to stop smoking and 7.5% (95% CI: 5.3-9.6%) had tried to stop smoking in the last year. Friends and family were the most frequent sources of help or counselling, and only a limited proportion of students received help from health professionals. Tobacco use and exposure to second-hand smoking is widespread among dental students in southern Brazil. Smoking-cessation initiatives targeting health care students are urgently needed. PMID- 25123049 TI - Daily torpor and hibernation in birds and mammals. AB - Many birds and mammals drastically reduce their energy expenditure during times of cold exposure, food shortage, or drought, by temporarily abandoning euthermia, i.e. the maintenance of high body temperatures. Traditionally, two different types of heterothermy, i.e. hypometabolic states associated with low body temperature (torpor), have been distinguished: daily torpor, which lasts less than 24 h and is accompanied by continued foraging, versus hibernation, with torpor bouts lasting consecutive days to several weeks in animals that usually do not forage but rely on energy stores, either food caches or body energy reserves. This classification of torpor types has been challenged, suggesting that these phenotypes may merely represent extremes in a continuum of traits. Here, we investigate whether variables of torpor in 214 species (43 birds and 171 mammals) form a continuum or a bimodal distribution. We use Gaussian-mixture cluster analysis as well as phylogenetically informed regressions to quantitatively assess the distinction between hibernation and daily torpor and to evaluate the impact of body mass and geographical distribution of species on torpor traits. Cluster analysis clearly confirmed the classical distinction between daily torpor and hibernation. Overall, heterothermic endotherms tend to be small; hibernators are significantly heavier than daily heterotherms and also are distributed at higher average latitudes (~35 degrees ) than daily heterotherms (~25 degrees ). Variables of torpor for an average 30 g heterotherm differed significantly between daily heterotherms and hibernators. Average maximum torpor bout duration was >30-fold longer, and mean torpor bout duration >25-fold longer in hibernators. Mean minimum body temperature differed by ~13 degrees C, and the mean minimum torpor metabolic rate was ~35% of the basal metabolic rate (BMR) in daily heterotherms but only 6% of BMR in hibernators. Consequently, our analysis strongly supports the view that hibernators and daily heterotherms are functionally distinct groups that probably have been subject to disruptive selection. Arguably, the primary physiological difference between daily torpor and hibernation, which leads to a variety of derived further distinct characteristics, is the temporal control of entry into and arousal from torpor, which is governed by the circadian clock in daily heterotherms, but apparently not in hibernators. PMID- 25123055 TI - Comparison of three methods for detection of gametocytes in Melanesian children treated for uncomplicated malaria. AB - BACKGROUND: Gametocytes are the transmission stages of Plasmodium parasites, the causative agents of malaria. As their density in the human host is typically low, they are often undetected by conventional light microscopy. Furthermore, application of RNA-based molecular detection methods for gametocyte detection remains challenging in remote field settings. In the present study, a detailed comparison of three methods, namely light microscopy, magnetic fractionation and reverse transcriptase polymerase chain reaction for detection of Plasmodium falciparum and Plasmodium vivax gametocytes was conducted. METHODS: Peripheral blood samples from 70 children aged 0.5 to five years with uncomplicated malaria who were treated with either artemether-lumefantrine or artemisinin-naphthoquine were collected from two health facilities on the north coast of Papua New Guinea. The samples were taken prior to treatment (day 0) and at pre-specified intervals during follow-up. Gametocytes were measured in each sample by three methods: i) light microscopy (LM), ii) quantitative magnetic fractionation (MF) and, iii) reverse transcriptase PCR (RTPCR). Data were analysed using censored linear regression and Bland and Altman techniques. RESULTS: MF and RTPCR were similarly sensitive and specific, and both were superior to LM. Overall, there were approximately 20% gametocyte-positive samples by LM, whereas gametocyte positivity by MF and RTPCR were both more than two-fold this level. In the subset of samples collected prior to treatment, 29% of children were positive by LM, and 85% were gametocyte positive by MF and RTPCR, respectively. CONCLUSIONS: The present study represents the first direct comparison of standard LM, MF and RTPCR for gametocyte detection in field isolates. It provides strong evidence that MF is superior to LM and can be used to detect gametocytaemic patients under field conditions with similar sensitivity and specificity as RTPCR. PMID- 25123056 TI - Pulmonary microvascular lesions regress in reperfused chronic thromboembolic pulmonary hypertension. AB - BACKGROUND: Pulmonary microvascular disease (PMD) develops in both occluded and non-occluded territories in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and may cause persistent pulmonary hypertension after pulmonary endarterectomy. Endothelin-1 (ET-1) and interleukin-6 (IL-6) are potential PMD severity biomarkers, but it remains unknown whether they are related to occluded or non-occluded territories. We assessed PMD and ET-1/IL-6 gene expression profiles in occluded and non-occluded territories with and without chronic lung reperfusion in an animal CTEPH model. METHODS: Chronic PH was induced in 10 piglets by left pulmonary artery (PA) ligation followed by weekly embolization of right lower lobe arteries with enbucrilate tissue adhesive for 5 weeks. At Week 6, 5 of 10 animals underwent left PA reperfusion. At Week 12, animals with and without reperfusion were compared with sham animals (n = 5). Hemodynamics, lung morphometry and ET-1/IL-6 gene expression profiles were assessed in the left lung (LL, occluded territories) and right upper lobe (RUL, non-occluded territories). RESULTS: At Week 12, mean PA pressure remained elevated without reperfusion (29.0 +/- 2.8 vs 27.0 +/- 1.1 mm Hg, p = 0.502), but decreased after reperfusion (30.0 +/- 1.5 vs 20.5 +/- 1.7 mm Hg, p = 0.013). Distal media thickness in the LL and RUL PAs and systemic vasculature to the LL were significantly lower in the reperfused and sham groups compared with the non reperfused group. PMD progression was related to ET-1 and IL-6 gene expression in the RUL and to the ET-A/ET-B gene expression ratio in the LL. CONCLUSIONS: PMD regressed in occluded and non-occluded territories after lung reperfusion. Changes in ET-1 and IL-6 gene expression were associated with PMD in non-occluded territories. PMID- 25123057 TI - Four types of Bifidobacteria trigger autophagy response in intestinal epithelial cells. AB - OBJECTIVES: To investigate the influence of gut microbiota on autophagy activation in intestinal epithelial cells (IEC) and to evaluate the IEC autophagy response to different types of Bifidobacteria. METHODS: IEC-18 cells were treated with lipopolysaccharide (LPS) derived from enteropathogenic Escherichia coli (EPEC) O127:B8 and culture medium supernatants of four types of Bifidobacteria. Transepithelial electrical resistance (TEER) was measured using an epithelial voltohmmeter. Autophagy was determined by transmission electron microscopy (TEM), the ratio of LC3-II to LC3-I and the persistence of both green fluorescent protein (GFP) and mCherry signals using a tandem mCherry-GFP-LC3 construct. The expression of Atg12-Atg5-Atg16 complex was measured by quantitative real-time polymerase chain reaction. RESULTS: EPEC-LPS significantly diminished the TEER of IEC compared with untreated controls by 45-55%. This reduction was not observed after treated with Bifidobacteria at all time points. Bifidobacteria could initiate the activation of autophagy in IEC, based on both the ratio of LC3-II to LC3-I and TEM. There was no difference in the influence of the four types of Bifidobacteria on the autophagy response. Compared with Bifidobacteria, IEC reacted to EPEC-LPS much more intensively by autophagy accumulation. More mCherry(+) LC3 autophagic puncta and increased expressions of autophagy genes Atg5, Atg12 and Atg16 could be detected after being treated with Bifidobacteria and EPEC-LPS. CONCLUSIONS: Bifidobacteria initiate autophagy activation in IEC. The Atg12-Atg5-Atg16 multimeric complex might participate in the activation of Bifidobacteria-induced cell autophagy. PMID- 25123058 TI - Electroneutralized amphiphilic triblock copolymer with a peptide dendron for efficient muscular gene delivery. AB - Hydrophilic-hydrophobic-hydrophilic triblock copolymers, such as Pluronic L64, P85, and P105, have attracted more attention due to their enhancement in muscular gene delivery. In the present study, a new kind of electroneutralized triblock copolymer, LPL, dendron G2(L-lysine-Boc)-PEG2k-dendron G2(L-lysine-Boc), was designed and investigated. This hydrophobic-hydrophilic-hydrophobic copolymer is composed of a structure reverse to that of L64, one of the most effective materials for intramuscular gene delivery so far. Our results showed that LPL exhibited good in vivo biocompatibility after intramuscular and intravenous administration. LPL mediated higher reporter gene expression than L64 in assays of beta-galactosidase (LacZ), luciferase, and fluorescent protein E2-Crimson. Furthermore, LPL-mediated mouse growth hormone expression significantly accelerated mouse growth within the first 10 days. Altogether, LPL-mediated gene expression in skeletal muscle exhibits the potential of successful gene therapy. The current study also presented an innovative way to design and construct new electroneutralized triblock copolymers for safe and effective intramuscular gene delivery. PMID- 25123059 TI - Relationship between patient-perceived vocal handicap and clinician-rated level of vocal dysfunction. AB - OBJECTIVES/HYPOTHESIS: The relationship between patient-reported vocal handicap and clinician-rated measures of vocal dysfunction is not understood. This study aimed to determine if a correlation exists between the Voice Handicap Index-10 (VHI-10) and the Voice Functional Communication Measure rating in the National Outcomes Measurement System (NOMS). STUDY DESIGN: Retrospective case series. METHODS: Four hundred and nine voice evaluations over 12 months at a tertiary voice center were reviewed. The VHI-10 and NOMS scores, diagnoses, and potential comorbid factors were collected and analyzed. RESULTS: For the study population as a whole, there was a moderate negative correlation between the NOMS rating and the VHI-10 (Pearson r = -0.57). However, for a given NOMS level, there could be considerable spread in the VHI-10. In addition, as the NOMS decreased stepwise below level 4, there was a corresponding increase in the VHI-10. However, a similar trend in VHI-10 was not observed for NOMS above level 4, indicating the NOMS versus VHI-10 correlation was not linear. Among diagnostic groups, the strongest correlation was found for subjects with functional dysphonia. The NOMS versus VHI-10 correlation was not affected by gender or the coexistence of a psychiatric diagnosis. CONCLUSIONS: A simple relationship between VHI-10 and NOMS rating does not exist. Patients with mild vocal dysfunction have a less direct relationship between their NOMS ratings and the VHI-10. These findings provide insight into the interpretation of patient-perceived and clinician-rated measures of vocal function and may allow for better management of expectations and patient counseling in the treatment of voice disorders. PMID- 25123060 TI - A new, microalgal DHA- and EPA-containing oil lowers triacylglycerols in adults with mild-to-moderate hypertriglyceridemia. AB - In this double-blind, parallel trial, 93 healthy adults with hypertriglyceridemia (triacylglycerols [TAG] 150-499 mg/dL) were randomized to receive either a nutritional oil derived from marine algae (DHA-O; 2.4 g/day docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA] in a 2.7:1 ratio), fish oil (FO; 2.0 g/day DHA and EPA in a 0.7:1 ratio), or a corn oil/soy oil control as 4-1g softgel capsules/day with meals for 14 weeks; and were instructed to maintain their habitual diet. Percent changes from baseline for DHA-O, FO, and control, respectively, were TAG (-18.9, -22.9, 3.5; p<0.001 DHA-O and FO vs. control), low density lipoprotein cholesterol (4.6, 6.8, -0.6; p<0.05 DHA-O and FO vs. control), and high-density lipoprotein cholesterol (4.3, 6.9, 0.6; p<0.05 FO vs. control). This study demonstrated that ingestion of microalgal DHA-O providing 2.4 g/day DHA+EPA lowered TAG levels to a degree that was not different from that of a standard fish oil product, and that was significantly more than for a corn oil/soy oil control. PMID- 25123061 TI - Heterogeneity in cord blood DHA concentration: towards an explanation. AB - This paper aimed to identify the dietary and non-dietary determinants of docosahexaenoic acid (DHA) levels in umbilical cord blood at delivery. DHA was measured in cord blood plasma phospholipids of 1571 participants from the DOMInO (DHA to Optimize Mother Infant Outcome) randomized controlled trial. Socioeconomic, lifestyle and clinical data relating to the mother and current pregnancy were obtained from all women and their relationships with cord blood DHA assessed. DHA concentrations in the cord plasma phospholipids at delivery covered a 3-4 fold range in both control and DHA groups. The total number of DHA rich intervention supplement capsules consumed over the course of pregnancy and gestational age at delivery individually explained 21% and 16% respectively of the variation in DHA abundance in the cord blood plasma phospholipids at delivery, but no other clinical or life-style factors explored in this study could account for >2% of the variation. Indeed, more than 65% of the variation remained unaccounted for even when all factors were included in the analysis. These data suggest that factors other than maternal DHA intake have an important role in determining cord blood DHA concentrations at delivery, and may at least partially explain the variation in the response of infants to maternal DHA supplementation reported in published trials. PMID- 25123062 TI - Gene expression of fatty acid transport and binding proteins in the blood-brain barrier and the cerebral cortex of the rat: differences across development and with different DHA brain status. AB - Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in brain cells but also transporting DHA from the blood across the blood-brain barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate the level of gene expression of fatty acid transport and fatty acid binding proteins in the cerebral cortex and at the BBB level during the perinatal period of active brain DHA accretion, at weaning, and until the adult age. We measured by real time RT-PCR the mRNA expression of different isoforms of fatty acid transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid binding proteins (FABPs) and the fatty acid transporter (FAT)/CD36 in cerebral cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14, 21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA dietary supplies (control, totally deficient or DHA-supplemented). In control rats, all the genes were expressed at the BBB level (P14 to P60), the mRNA levels of FABP5 and ACSL3 having the highest values. Age-dependent differences included a systematic decrease in the mRNA expressions between P14-P21 and P60 (2 to 3 fold), with FABP7 mRNA abundance being the most affected (10-fold). In the cerebral cortex, mRNA levels varied differently since FATP4, ACSL3 and ACSL6 and the three FABPs genes were highly expressed. There were no significant differences in the expression of the 10 genes studied in n-3 deficient or DHA supplemented rats despite significant differences in their brain DHA content, suggesting that brain DHA uptake from the blood does not necessarily require specific transporters within cerebral endothelial cells and could, under these experimental conditions, be a simple passive diffusion process. PMID- 25123064 TI - Fluorescence in-situ hybridization identifies Mastermind-like 2 (MAML2) rearrangement in odontogenic cysts with mucous prosoplasia: a pilot study. AB - AIMS: The pathogenesis of intraosseous mucoepidermoid carcinoma (IMEC) remains unknown. Coexistence with odontogenic cysts (ODC) has been reported in 32-48% of IMEC. Furthermore, prosoplastic mucous cells are often seen in the epithelial lining of ODCs. MECT1-MAML2 fusion transcripts have been identified in >66% of salivary gland MEC cases. The aim of this study was to investigate the presence of MAML2 rearrangement in ODCs featuring mucous prosoplasia. METHODS AND RESULTS: Ten cases of ODC with a mucous cell component and three cases of IMEC were evaluated using fluorescence in-situ hybridization. All cases occurred in the mandible. The ODCs exhibited a M:F ratio of 4:1 (mean age 49.2 years), while all IMECs occurred in women (mean age 68.3 years). All three IMECs demonstrated MAML2 rearrangement, in 26-61% of tumour cells. Successful hybridization was observed in nine of 10 cases of ODC. In two of these nine, there was MAML2 rearrangement in 12% and 24% of the lining epithelial cells, while three of the nine showed rearrangement in 7-8% of cells; the remaining four cases were negative. CONCLUSIONS: We identified MAML2 rearrangements in five of nine ODCs lined by mucus-secreting cells. This suggests that at least a subset of ODCs with mucous prosoplasia are characterized by molecular events considered diagnostic for intraosseous and extraosseous MEC. PMID- 25123065 TI - [Comorbidity in 207 cannabis users in a specific outpatient setting]. AB - BACKGROUND: Health care seeking for a problematic use of cannabis is in progress in France. OBJECTIVES: The aim is to assess the addictive and psychiatric comorbidity in cannabis users seen in the specific setting at the Lariboisiere hospital. METHOD: Two hundred and seven cannabis users were included from January 2004 to December 2009. Twelve-month and lifetime diagnosis of abuse and dependence (cannabis, alcohol, cocaine/crack) (DSM-IV), current and lifetime mood disorders, anxiety disorders, eating disorders and psychotic disorders were assessed (Mini-International Neuropsychiatric Interview). Logistic regression analyses identified adjusted odds ratios associated with the gender and the health care seeking (P=0.01). RESULTS: One hundred and forty-seven men (71%) and 60 women (29%), 29.3+/-8.6 years (15.2-51.6 years). Most of the outpatients ask for health care themselves (59.7%), whereas 19.4% are asked to seek health care by relatives (19.4%) or because of an academic, health or justice injunction (20.4%). In total, 49.3% of the outpatients are single, 35.7% are cohabitating, 9.3% are married and 6.3% are separated/divorced. About 20.4% of the outpatients are students, 35.7% have a professional activity, 19% are jobless, 2.4% are impaired, 0.5% are retired, at home and 12.1% do not have an official income. Twelve-month and lifetime prevalence of abuse/dependence are: cannabis (10.1/82.1% and 8.7/88.4%), alcohol (9.7/8.7% and 19.3/18.8%), cocaine/crack (2.4/3.4% and 4.8/11.6%). The mean duration of cannabis dependence for the current dependent users is 8.4+/-5.8 years. The mean number of "joints" during the last 6 months is 6+/-4.3, the mean amount of cannabis per week is 12.5+/ 11.3g. About 51.3% of the dependent users report externalized and/or internalized disorders at school during childhood and adolescence. In total, 19.4% of the dependent users have a suicide attempt history and 18.9% have a psychiatric hospitalisation history, more frequently women (P<0.01 and P=0.02). About 73.8% have a psychologist or psychiatrist care history. In total, 38.1% of users have at least one current mood disorder, females more frequently than males (P<0.001). Current and lifetime prevalence of mood disorders are: major depressive disorder (MDD) (29.1% and 57.1%); current dysthymia (20.3%); hypomania (1.9 and 6.7%); mania (2.9 and 12.8%). Females have more frequently than males current and lifetime MDD (P<0.001). About 53.2% of users have at least one current anxiety disorder, females more frequently than males (P<0.001). Current and lifetime prevalence of anxiety disorders are: panic disorder (10 and 16.4%); agoraphobia (13.9 and 17.4%); social phobia (26.9 and 32.8%); obsessive-compulsive disorder (9.5 and 12.9%); post-traumatic stress disorder (PTSD) (6.5 and 16.4%); current generalized anxiety disorder (26.8%). Females have more frequently current and lifetime: agoraphobia (P=0.01 and P<0.001); PTSD (P<0.001); current social phobia (P=0.049). Current and lifetime eating disorders prevalence are: anorexia (0 and 1.5%); bulimia (4 and 8%); females more frequently have bulimia (P=0.02 and P<0.001). In total, 4.8% have a psychotic disorder. Adjusted odds ratios of associated variables to gender (women/men) are lifetime MDD OR=4.71 [2.1-10.61] (P<0.001) and later age of onset of cannabis abuse OR=1.1 [1.04-1.17] (P=0.002). Adjusted odds ratios associated with personal health care seeking compared to a non personal motivated health care seeking are the numbers of criteria of 12 month cannabis dependence OR=1.26 [1.06-1.51] (P=0.009) and age OR=1.07 [1.03 1.12] (P=0.002). CONCLUSION: Our survey confirms the high mood and anxiety disorders comorbidity in cannabis dependent users seen in a specific setting and underlines the need to evaluate those disorders. PMID- 25123063 TI - MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1. AB - BACKGROUND: The IFN-alpha-inducible restriction factor MxB blocks HIV-1 infection after reverse transcription but prior to integration. Genetic evidence suggested that capsid is the viral determinant for restriction by MxB. This work explores the ability of MxB to bind to the HIV-1 core, and the role of capsid-binding in restriction. RESULTS: We showed that MxB binds to the HIV-1 core and that this interaction leads to inhibition of the uncoating process of HIV-1. These results identify MxB as an endogenously expressed protein with the ability to inhibit HIV 1 uncoating. In addition, we found that a benzimidazole-based compound known to have a binding pocket on the surface of the HIV-1 capsid prevents the binding of MxB to capsid. The use of this small-molecule identified the MxB binding region on the surface of the HIV-1 core. Domain mapping experiments revealed the following requirements for restriction: 1) MxB binding to the HIV-1 capsid, which requires the 20 N-terminal amino acids, and 2) oligomerization of MxB, which is mediated by the C-terminal domain provides the avidity for the interaction of MxB with the HIV-1 core. CONCLUSIONS: Overall our work establishes that MxB binds to the HIV-1 core and inhibits the uncoating process of HIV-1. Moreover, we demonstrated that HIV-1 restriction by MxB requires capsid binding and oligomerization. PMID- 25123066 TI - A multiplanar complex resection of a low-grade chondrosarcoma of the distal femur guided by K-wires previously inserted under CT-guide: a case report. AB - BACKGROUND: In muscular skeletal oncology aiming to achieve wide surgical margin is one of the main factors influencing patient prognosis. In cases where lesions are either meta or epiphyseal, surgery most often compromises joint integrity and stability because muscles, tendons and ligaments are involved in wide resection. When lesions are well circumscribed they can be completely resected by performing multi-planar osteotomies guided by computer-assisted navigation. We describe a case of low-grade chondrosarcoma of the distal femur where a simple but effective technique was useful to perform complex multiplanar osteotomies. No similar techniques are reported in the literature. CASE PRESENTATION: A 57 year-old Caucasian female was referred to our department for the presence of a distal femur chondrosarcoma. A resection with the presenting technique was scheduled. The first step consists of inserting several K-wires under CT-scan control to delimitate the tumor; the second step consists of tumor removal: in operative theatre, following surgical access, k-wires are used as guide positioning; scalpels are externally placed to k-wires to perform a safe osteotomy. CONCLUSIONS: Computed assisted resections can be considered the most advantageous method to reach the best surgical outcome; unfortunately navigation systems are only available in specialized centres. The present technique allows for a multiplanar complex resection when navigation systems are not available. This technique can be applied in low-grade tumours where a minimal wide margin can be considered sufficient. PMID- 25123067 TI - Echinococcus as a model system: biology and epidemiology. AB - The introduction of Echinococcus to Australia over 200 years ago and its establishment in sheep rearing areas of the country inflicted a serious medical and economic burden on the country. This resulted in an investment in both basic and applied research aimed at learning more about the biology and life cycle of Echinococcus. This research served to illustrate the uniqueness of the parasite in terms of developmental biology and ecology, and the value of Echinococcus as a model system in a broad range of research, from fundamental biology to theoretical control systems. These studies formed the foundation for an international, diverse and ongoing research effort on the hydatid organisms encompassing stem cell biology, gene regulation, strain variation, wildlife diseases and models of transmission dynamics. We describe the development, nature and diversity of this research, and how it was initiated in Australia but subsequently has stimulated much international and collaborative research on Echinococcus. PMID- 25123068 TI - Genetic diversity of the Chinese liver fluke Clonorchis sinensis from Russia and Vietnam. AB - Clonorchiasis is a parasitic disease of high public health importance in many countries in southeastern Asia and is caused by the Chinese liver fluke Clonorchis sinensis. However, the genetic structure and demographic history of its populations has not been sufficiently studied throughout the geographic range of the species and available data are based mainly on partial gene sequencing. In this study, we explored the genetic diversity of the complete 1560 bp cytochrome c oxidase subunit 1 (cox1) gene sequence for geographically isolated C. sinensis populations in Russia and Vietnam, to our knowledge for the first time. The results demonstrated low nucleotide and high haplotype differentiation within and between the two compared regions and a clear geographical vector for the distribution of genetic diversity patterns among the studied populations. These results suggest a deep local adaptation of the parasite to its environment including intermediate hosts and the existence of gene flow across the species' range. Additionally, we have predicted an amino acid substitution in the functional site of the COX1 protein among the Vietnamese populations, which were reported to be difficult to treat with praziquantel. The haplotype networks consisted of several region-specific phylogenetic lineages, the formation of which could have occurred during the most extensive penultimate glaciations in the Pleistocene Epoch. The patterns of genetic diversity and demographics are consistent with population growth of the liver fluke in the late Pleistocene following the Last Glacial Maximum, indicating the lack of a population bottleneck during the recent past in the species' history. The data obtained have important implications for understanding the phylogeography of C. sinensis, its host-parasite interactions, the ability of this parasite to evolve drug resistance, and the epidemiology of clonorchiasis under global climate change. PMID- 25123069 TI - Four-decade-old mummified umbilical tissue making retrospective molecular diagnosis of ornithine carbamoyltransferase deficiency. PMID- 25123070 TI - Factors influencing household uptake of improved solid fuel stoves in low- and middle-income countries: a qualitative systematic review. AB - Household burning of solid fuels in traditional stoves is detrimental to health, the environment and development. A range of improved solid fuel stoves (IS) are available but little is known about successful approaches to dissemination. This qualitative systematic review aimed to identify factors that influence household uptake of IS in low- and middle-income countries. Extensive searches were carried out and studies were screened and extracted using established systematic review methods. Fourteen qualitative studies from Asia, Africa and Latin-America met the inclusion criteria. Thematic synthesis was used to synthesise data and findings are presented under seven framework domains. Findings relate to user and stakeholder perceptions and highlight the importance of cost, good stove design, fuel and time savings, health benefits, being able to cook traditional dishes and cleanliness in relation to uptake. Creating demand, appropriate approaches to business, and community involvement, are also discussed. Achieving and sustaining uptake is complex and requires consideration of a broad range of factors, which operate at household, community, regional and national levels. Initiatives aimed at IS scale up should include quantitative evaluations of effectiveness, supplemented with qualitative studies to assess factors affecting uptake, with an equity focus. PMID- 25123071 TI - Vasculogenic mimicry: a new prognostic sign of human osteosarcoma. AB - Vasculogenic mimicry (VM), a formation of nonendothelial microvascular channels, has been generally recognized as a new pattern of neovascularization in aggressive malignancies. However, whether VM is present and clinically significant in osteosarcoma remains unknown. We identified VM by CD34/periodic acid-Schiff double staining of osteosarcoma specimens before chemotherapy and investigated its prognostic implications. Tumors were also immunohistochemically stained for focal adhesion kinase (FAK) and migration inducing gene 7 (Mig-7) to determine whether these markers are associated with the occurrence of VM. VM was found in 15 of 66 osteoblastic-type osteosarcoma samples (22.7%), and the incidence of VM did not differ with respect to patient sex, age, tumor size, tumor site, surgical type, or histologic response to preoperative chemotherapy. However, Kaplan-Meier survival analysis determined that the presence of VM and the tumor necrosis rate after preoperative chemotherapy are associated with both the overall survival (P = .011 and P = .040, respectively) and metastasis-free survival (P = .002 and P = .045, respectively). Furthermore, Cox proportional hazards analysis showed that the presence of VM and the histologic response to preoperative chemotherapy were independent indicators for both poor overall survival (P = .007 and P = .024, respectively) and poor metastasis-free survival (P = .002 and P = .027, respectively). The expression level of FAK and Mig-7 were higher in the VM group than the non-VM group (P = .017 and P = .021, respectively). These results demonstrate the presence of VM in osteoblastic osteosarcoma and suggest that VM is an unfavorable prognostic factor with FAK and Mig-7 expressions as a potential mechanism of VM formation in osteosarcoma. PMID- 25123072 TI - Leukocyte chemotactic factor 2 amyloidosis can be reliably diagnosed by immunohistochemical staining. PMID- 25123073 TI - Sclerosing epithelioid fibrosarcoma presenting as intraabdominal sarcomatosis with a novel EWSR1-CREB3L1 gene fusion. AB - We report a case of intraabdominal sclerosing epithelioid fibrosarcoma (SEF) with a t (11;22)(p11.2;q12.2) Ewing sarcoma breakpoint region 1-cAMP-responsive element-binding protein 3-like 1 translocation. A 43-year old man presented with massive ascites and shortness of breath. Imaging studies revealed a large mesenteric-based mass with extensive omental/peritoneal disease. After resection and cytoreductive surgery, the tumor recurred with metastasis to the lungs; the patient is still alive with disease. Histologically, there was a uniform population of epithelioid cells arranged in cords and nests, embedded in a dense collagenous matrix; no areas of low-grade fibromyxoid sarcoma were identified. All immunohistochemical markers were nonreactive. Fluorescence in situ hybridization studies showed rearrangement of Ewing sarcoma breakpoint region 1. Genomic profiling by clinical grade next-generation sequencing revealed a fusion gene between intron 11 of Ewing sarcoma breakpoint region 1 (22q12.2) and intron 5 of cAMP-responsive element-binding protein 3-like 1 (11p11.2). This is the first report of "pure" or true SEF presenting as intraabdominal sarcomatosis with confirmation of the recently described unique Ewing sarcoma breakpoint region 1 cAMP-responsive element-binding protein 3-like 1 gene fusion in SEF without areas of low-grade fibromyxoid sarcoma. PMID- 25123074 TI - Choledochal cysts: a clinicopathologic study of 36 cases with emphasis on the morphologic and the immunohistochemical features of premalignant and malignant alterations. AB - Choledochal cysts (CDCs) are believed to represent a risk factor for the development of neoplasia. However, the frequency and morphology of neoplastic changes have not been systematically studied, especially in North America. Our aims were to study the frequency and morphology of preneoplastic/neoplastic changes of CDCs. Thirty-six cysts were subjected to clinicopathological analyses. Metaplasia was found in 14 of 35, of which 9 had biliary intraepithelial neoplasia (BilIN). Of the 14 with metaplasia, 13 showed pyloric gland; 5, intestinal; and 2, squamous. BilINs included 6 BilIN-1, 2 BilIN-2, and 2 BilIN-3. Carcinoma was identified in 5 cases of which 3 were associated with metaplasia and BilIN. Only 1 of 18 cases without metaplasia had BilIN, and none had carcinoma (P = .0008). There was a trend toward more BilIN and carcinoma with intestinal rather than with pyloric gland metaplasia. All cases with metaplasia or/and BilIN were negative for MUC1. All cases with intestinal metaplasia were positive for CK20, CDX2, and MUC2, whereas cases with pyloric gland were positive for MUC6. MUC1, CEA, and B72.3 were positive only in carcinoma. There was a trend toward increasing p53 and Ki-67 from metaplasia to BilIN to carcinoma. Four of 5 patients with carcinoma died, and one was alive with disease. All others were free of disease except for one who developed new cysts. CDCs are associated with a high rate of BilIN (28.5%) and carcinoma (14.3%). CDCs show a sequence of tumor progression from metaplasia to BilIN and carcinoma. PMID- 25123075 TI - Leukocyte chemotactic factor 2 amyloidosis cannot be reliably diagnosed by immunohistochemical staining--reply. PMID- 25123077 TI - Mimickers of neoplasm on abdominal and pelvic CT. AB - PURPOSE: The radiologist can encounter benign significant imaging findings on computed tomography that can be incorrectly interpreted as neoplasm. The authors review several benign findings and demonstrate several methods to differentiate these findings from more sinister pathology. CONCLUSION: It is imperative for the radiologist to be cognizant of and how to correctly identify mimickers of pathology so that unnecessary interventions and surgeries are avoided. PMID- 25123076 TI - Colchicine for acute gout. AB - BACKGROUND: This is an update of a Cochrane review first published in 2006. Gout is one of the most common rheumatic diseases worldwide. Despite the use of colchicine as one of the first-line therapies for the treatment of acute gout, evidence for its benefits and harms is relatively limited. OBJECTIVES: To evaluate the benefits and harms of colchicine for the treatment of acute gout. SEARCH METHODS: We searched the following electronic databases from inception to April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. We did not impose any date or language restrictions in the search. We also handsearched conference proceedings of the American College of Rheumatology and the European League against Rheumatism (2010 until 2013) and reference lists of identified studies. We searched the clinical trials register clinicaltrials.gov and the WHO trials register. SELECTION CRITERIA: We considered published randomised controlled trials (RCTs) and controlled clinical trials (CCTs) evaluating colchicine therapy compared with another therapy (active or placebo) in acute gout. The primary benefit outcome of interest was pain, defined as a proportion with 50% or greater decrease in pain, and the primary harm outcome was study participants withdrawal due to adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results for relevant studies, extracted data into a standardised form and assessed the risk of bias of included studies. We pooled data if deemed to be sufficiently clinically homogeneous. We assessed the quality of the body of evidence for each outcome using the GRADE approach. MAIN RESULTS: Two RCTs (124 participants) were included in this updated review, including one new RCT. We considered one trial to be at low risk of bias, while we considered the newly included trial to be at unclear risk of bias. Both trials included a placebo and a high-dose colchicine arm, although the colchicine regimens varied. In one trial 0.5 mg colchicine was given every two hours until there was either complete relief of symptoms or toxicity and the total doses were not specified. In the other trial a total of 4.8 mg colchicine was given over six hours. The newly identified trial also included a low-dose colchicine arm (total 1.8 mg over one hour).Based upon pooled data from two trials (124 participants), there is low-quality evidence that a greater proportion of people receiving high-dose colchicine experience a 50% or greater decrease in pain from baseline up to 32 to 36 hours compared with placebo (35/74 in the high-dose colchicine group versus 12/50 in the placebo group (risk ratio (RR) 2.16, 95% confidence interval (CI) 1.28 to 3.65), with a number needed to treat to benefit (NNTB) of 4 (95% CI 3 to 12). However, the total number of adverse events (diarrhoea, vomiting or nausea) is greater in those who receive high-dose colchicine versus placebo (62/74 in the high-dose colchicine group versus 11/50 in the placebo group (RR 3.81, 95% CI 2.28 to 6.38), with a number needed to treat to harm (NNTH) of 2 (95% CI 2 to 5). Only one trial included reduction of inflammation as part of a composite measure comprising pain, tenderness, swelling and erythema, each graded on a four-point scale (none 0 to severe 3) to derive a maximum score for any one joint of 12. They reported the proportion of people who achieved a 50% reduction in this composite score. Based upon one trial (43 participants), there was low-quality evidence that more people in the high-dose colchicine group had a 50% or greater decrease in composite score from baseline up to 32 to 36 hours than people in the placebo group (11/22 in the high-dose colchicine group versus 1/21 in the placebo group (RR 10.50, 95% CI 1.48 to 74.38) and 45% absolute difference).Based upon data from one trial (103 participants), there was low-quality evidence that low-dose colchicine is more efficacious than placebo with respect to the proportion of people who achieve a 50% or greater decrease in pain from baseline to 32 to 36 hours (low dose colchicine 31/74 versus placebo 5/29 (RR 2.43, 95% CI 1.05 to 5.64)), with a NNTB of 5 (95% CI 2 to 20). There are no additional harms in terms of adverse events (diarrhoea, nausea or vomiting) with low-dose colchicine compared to placebo (19/74 and 6/29 respectively (RR 1.24, 95% CI 0.55 to 2.79)).Based upon data from one trial (126 participants), there is low-quality evidence that there are no additional benefits in terms of the proportion of people achieving 50% or greater decrease in pain from baseline up to 32 to 36 hours with high-dose colchicine compared to low-dose (19/52 and 31/74 respectively (RR 0.87, 95% CI 0.56 to 1.36). However, there were statistically significantly more adverse events in those who received high-dose colchicine (40/52 versus 19/74 in the low dose group (RR 3.00, 95% CI 1.98 to 4.54)), with a NNTH of 2 (95% CI 2 to 3).No trials reported function of the target joint, patient-reported global assessment of treatment success, health-related quality of life or withdrawals due to adverse events. We identified no studies comparing colchicine to non-steroidal anti-inflammatory drugs (NSAIDs) or other active treatments such as glucocorticoids (by any route). AUTHORS' CONCLUSIONS: Based upon only two published trials, there is low-quality evidence that low-dose colchicine is likely to be an effective treatment for acute gout. We downgraded the evidence because of a possible risk of selection and reporting biases and imprecision. Both high and low-dose colchicine improve pain when compared to placebo. While there is some uncertainty around the effect estimates, compared with placebo, high-dose but not low-dose colchicine appears to result in a statistically significantly greater number of adverse events. Therefore low-dose colchicine may be the preferred treatment option. There are no trials about the effect of colchicine in populations with comorbidities or in comparison with other commonly used treatments, such as NSAIDs and glucocorticoids. PMID- 25123078 TI - High-grade undifferentiated sarcomas of the uterus: diagnosis, outcomes, and new treatment approaches. AB - High-grade undifferentiated sarcomas (HGUS) are rare malignancies accounting for 6 % of all uterine sarcomas and have a very poor outcome. Histological classification of HGUS is currently debated as a subgroup with uniform nucleoli, and frequently YWHAE-FAM22 transcript has been described, constituting a potential target for new therapies. In localized HGUS, surgery involving total hysterectomy and bilateral oophorectomy is recommended. Adjuvant radiotherapy has recently been suggested in a retrospective study to decrease local recurrence and improve survival versus observation in localized HGUS. In metastatic or recurrent disease, chemotherapy with doxorubicin with or without ifosfamide constitutes the standard of care. Gemcitabine plus docetaxel also seems to be an interesting alternative. Targeted therapies such as pazopanib are now available for soft tissue sarcomas and so could be proposed for uterine sarcoma patients after first or second-line chemotherapy in the metastatic phase. Further investigations are needed to determine their indications and targets. A European Organisation for Research and Treatment of Cancer (EORTC) randomized trial testing maintenance therapy with cabozantinib after first-line chemotherapy in HGUS is ongoing. PMID- 25123080 TI - The role of individual and collective moral disengagement in peer aggression and bystanding: a multilevel analysis. AB - This study investigates the relationships between individual and collective moral disengagement and aggression-related behaviors (peer aggression, defending, and passive bystanding) among 918 adolescents (55.8% boys; M age = 14.1 years, SD = 1.1). Hierarchical linear modeling showed that, at the individual level, aggressive behavior was significantly explained by both individual moral disengagement and student perceived collective moral disengagement, which was also positively associated with defending. Student perceived collective moral disengagement moderated the link between individual moral disengagement and peer aggression. At the class level, classroom collective moral disengagement explained between-class variability in all the three aggression-related behaviors. These results extend previous research by demonstrating the role of collective moral disengagement at the individual and the class levels and have potential implications for interventions. PMID- 25123079 TI - Cancer-promoting effects of microbial dysbiosis. AB - Humans depend on our commensal bacteria for nutritive, immune-modulating, and metabolic contributions to maintenance of health. However, this commensal community exists in careful balance that, if disrupted, enters dysbiosis; this has been shown to contribute to the pathogenesis of colon, gastric, esophageal, pancreatic, laryngeal, breast, and gallbladder carcinomas. This development is closely tied to host inflammation, which causes and is aggravated by microbial dysbiosis and increases vulnerability to pathogens. Advances in sequencing technology have increased our ability to catalog microbial species associated with various cancer types across the body. However, defining microbial biomarkers as cancer predictors presents multiple challenges, and existing studies identifying cancer-associated bacteria have reported inconsistent outcomes. Combining metabolites and microbiome analyses can help elucidate interactions between gut microbiota, metabolism, and the host. Ultimately, understanding how gut dysbiosis impacts host response and inflammation will be critical to creating an accurate picture of the role of the microbiome in cancer. PMID- 25123081 TI - Stress sensitivity interacts with depression history to predict depressive symptoms among youth: prospective changes following first depression onset. AB - Predictors of depressive symptoms may differ before and after the first onset of major depression due to stress sensitization. Dependent stressors, or those to which characteristics of individuals contribute, have been shown to predict depressive symptoms in youth. The current study sought to clarify how stressors' roles may differ before and after the first depressive episode. Adolescents (N = 382, aged 11 to 15 at baseline) were assessed at baseline and every 3 months over the course of 2 years with measures of stressors and depressive symptoms. Semi structured interviews were conducted every 6 months to assess for clinically significant depressive episodes. Hierarchical linear modeling showed a significant interaction between history of depression and idiographic fluctuations in dependent stressors to predict prospective elevations of symptoms, such that dependent stressors were more predictive of depressive symptoms after onset of disorder. Independent stressors predicted symptoms, but the strength of the association did not vary by depression history. These results suggest a synthesis of dependent stress and stress sensitization processes that might maintain inter-episode depressive symptoms among youth with a history of clinical depression. PMID- 25123082 TI - Low-dose decitabine induces MAGE-A expression and inhibits invasion via suppression of NF-kappaB2 and MMP2 in Eca109 cells. AB - Decitabine, a demethylating drug, is the first-line treatment for myelodysplastic syndromes and gains better overall survival, which is based on epigenetic mechanism. Activated by promoter demethylation, melanoma-associated antigens-A (MAGE-A), cancer-testis antigens are attractive targets for immunotherapy. Our purpose was to investigate whether decitabine could show anti-tumor effects for esophageal cancer and explore its mechanism. In addition, we aimed to examine its modulation for most MAGE-A members. The results showed the baseline expression were MAGE-A2, -3,-9, and -10 in Eca109 cells and decitabine (0.5 MUM) could induce MAGE-A8 and -A4 whereas reduce MAGE-A9 and -A10. Moreover, decitabine (0.5 MUM) inhibited cell proliferation, migration and invasive ability by 15%, 34% and 47.2%, respectively and decreased expressions of NF-kappaB2 and MMP2. Our results demonstrated that low-dose decitabine induced the expression of MAGE-A8 and -A4, and inhibited cell invasion through decreasing expression of MMP2 and NF-kappaB2, which provides possibilities for combing decitabine with immunotherapy targeting MAGE-A to treat advanced esophageal squamous cell carcinoma. PMID- 25123083 TI - Superparamagnetic iron oxide nanoparticles impair endothelial integrity and inhibit nitric oxide production. AB - Superparamagnetic iron oxide nanoparticles (SPION) are widely used both clinically and experimentally for diverse in vivo applications, such as contrast enhancement in magnetic resonance imaging, hyperthermia and drug delivery. Biomedical applications require particles to have defined physical and chemical properties, and to be stable in biological media. Despite a suggested low cytotoxic action, adverse reactions of SPION in concentrations relevant for biomedical use have not yet been studied in sufficient detail. In the present work we employed Endorem(r), dextran-stabilized SPION approved as an intravenous contrast agent, and compared its action to a set of other nanoparticles with potential for magnetic resonance imaging applications. SPION in concentrations relevant for in vivo applications were rapidly taken up by endothelial cells and exhibited no direct cytotoxicity. Electric cell impedance sensing measurements demonstrated that SPION, but not BaSO4/Gd nanoparticles, impaired endothelial integrity, as was confirmed by increased intercellular gap formation in endothelial monolayers. These structural changes induced the subcellular translocation and inhibition of the cytoprotective and anti-atherosclerotic enzyme endothelial NO-synthase and reduced NO production. Lipopolysaccharide induced inflammatory NO production of macrophages was not affected by SPION. In conclusion, our data suggest that SPION might substantially alter endothelial integrity and function at therapeutically relevant doses, which are not cytotoxic. PMID- 25123084 TI - The influence of social anxiety on the body checking behaviors of female college students. AB - Social anxiety and eating pathology frequently co-occur. However, there is limited research examining the relationship between anxiety and body checking, aside from one study in which social physique anxiety partially mediated the relationship between body checking cognitions and body checking behavior (Haase, Mountford, & Waller, 2007). In an independent sample of 567 college women, we tested the fit of Haase and colleagues' foundational model but did not find evidence of mediation. Thus we tested the fit of an expanded path model that included eating pathology and clinical impairment. In the best-fitting path model (CFI=.991; RMSEA=.083) eating pathology and social physique anxiety positively predicted body checking, and body checking positively predicted clinical impairment. Therefore, women who endorse social physique anxiety may be more likely to engage in body checking behaviors and experience impaired psychosocial functioning. PMID- 25123086 TI - Telomerase reverse transcriptase promoter mutation is an early somatic genetic alteration in the transformation of premalignant nodules in hepatocellular carcinoma on cirrhosis. AB - Genetic determinants of the early steps of carcinogenesis on cirrhosis are still poorly understood. We aimed to evaluate the occurrence of telomerase reverse transcriptase (TERT) promoter mutations in the transformation of cirrhotic nodules into hepatocellular carcinoma (HCC). We analyzed a series of 268 liver samples, including 96 nodules developed in 58 patients with cirrhosis and 114 additional cirrhosis. All samples were screened for TERT promoter mutations, and in 31 nodules, for 10 genes recurrently mutated in HCC. Immunohistochemistry (IHC) analyses were performed for glypican 3, glutamine synthase, and heat shock protein 70. Six liver pathologists reviewed all the samples. Among The 96 nodules, 88 were firmly diagnosed as low-grade dysplastic nodules (LGDNs; 32 cases), high-grade dysplastic nodules (HGDNs; 16 cases), early HCC (eHCC; 23 cases), or small and progressed HCC in 17 cases. The agreement between the initial diagnosis from pathological report and the final expert consensus report was moderate for the diagnosis of benign versus malignant nodules (weighted kappa = 0.530). TERT promoter mutations were highly related to the step-wise hepatocarcinogenesis because mutations were identified in 6% of LGDNs, 19% of HGDNs, 61% of eHCCs, and 42% of small and progressed HCC. TERT promoter mutation is the most frequent molecular alteration in eHCC given that the IHC criteria for diagnosis of malignancy were found in only 39% of the cases. TERT promoter mutation was also the earliest genetic alteration because mutations in 10 other genes were only identified in 28% of the small and progressed HCC. CONCLUSION: Frequency of TERT promoter mutations rapidly increases during the different steps of the transformation of premalignant lesions into HCC on cirrhosis. Consequently, somatic TERT promoter mutation is a new biomarker predictive of transformation of premalignant lesions into HCC. PMID- 25123087 TI - High-throughput continuous flow femtosecond laser-assisted cell optoporation and transfection. AB - We present a femtosecond-laser based nanoprocessing system for transient optical cell membrane poration to allow the introduction of foreign molecules into the interior of a cell with very high throughput. In the setup, cells flow through a micro-flow tube for spatial confinement and are simultaneously targeted by fs laser radiation. Beam-shaping generates a focal geometry along a line which is scanned across the micro-flow cell to increase the number of reachable cells. Successful cell membrane poration was observed indirectly by cell transfection even with cell-light interaction times in the millisecond range. The system was characterized by experiments with Chinese hamster ovary cells regarding cell viability, the uptake of extrinsic molecules and cell transfection efficiency. The continuous flow of cells enables a tremendous increase of cell throughput compared to previous nonflow approaches by treating millions of cells, although with only limited efficiency. The setup opens the possibility to realize a completely automated high-throughput laser-assisted cell-poration system which could be integrated in lab-on-a-chip devices. PMID- 25123085 TI - Genetic diversity of porcine group A rotavirus strains in the UK. AB - Rotavirus is endemic in pig farms where it causes a loss in production. This study is the first to characterise porcine rotavirus circulating in UK pigs. Samples from diarrheic pigs with rotavirus enteritis obtained between 2010 and 2012 were genotyped in order to determine the diversity of group A rotavirus (GARV) in UK pigs. A wide range of rotavirus genotypes were identified in UK pigs: six G types (VP7); G2, G3, G4, G5, G9 and G11 and six P types (VP4); P[6], P[7], P[8], P[13], P[23], and P[32]. With the exception of a single P[8] isolate, there was less than 95% nucleotide identity between sequences from this study and any available rotavirus sequences. The G9 and P[6] genotypes are capable of infecting both humans and pigs, but showed no species cross-over within the UK as they were shown to be genetically distinct, which suggested zoonotic transmission is rare within the UK. We identified the P[8] genotype in one isolate, this genotype is almost exclusively found in humans. The P[8] was linked to a human Irish rotavirus isolate in the same year. The discovery of human genotype P[8] rotavirus in a UK pig confirms this common human genotype can infect pigs and also highlights the necessity of surveillance of porcine rotavirus genotypes to safeguard human as well as porcine health. PMID- 25123088 TI - Genotoxic, epigenetic, and transcriptomic effects of tamoxifen in mouse liver. AB - Tamoxifen is a non-steroidal anti-estrogenic drug widely used for the treatment and prevention of breast cancer in women; however, there is evidence that tamoxifen is hepatocarcinogenic in rats, but not in mice. Additionally, it has been reported that tamoxifen may cause non-alcoholic fatty liver disease (NAFLD) in humans and experimental animals. The goals of the present study were to (i) investigate the mechanisms of the resistance of mice to tamoxifen-induced hepatocarcinogenesis, and (ii) clarify effects of tamoxifen on NAFLD-associated liver injury. Feeding female WSB/EiJ mice a 420 p.p.m. tamoxifen-containing diet for 12 weeks resulted in an accumulation of tamoxifen-DNA adducts, (E)-alpha (deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N(2)-yl) N-desmethyltamoxifen (dG-DesMeTAM), in the livers. The levels of hepatic dG-TAM and dG-DesMeTAM DNA adducts in tamoxifen-treated mice were 578 and 340 adducts/108 nucleotides, respectively, while the extent of global DNA and repetitive elements methylation and histone modifications did not differ from the values in control mice. Additionally, there was no biochemical or histopathological evidence of NAFLD-associated liver injury in mice treated with tamoxifen. A transcriptomic analysis of differentially expressed genes demonstrated that tamoxifen caused predominantly down-regulation of hepatic lipid metabolism genes accompanied by a distinct over-expression of the lipocalin 13 (Lcn13) and peroxisome proliferator receptor gamma (Ppargamma), which may prevent the development of NAFLD. The results of the present study demonstrate that the resistance of mice to tamoxifen-induced liver carcinogenesis may be associated with its ability to induce genotoxic alterations only without affecting the cellular epigenome and an inability of tamoxifen to induce the development of NAFLD. PMID- 25123091 TI - Azavinylidenephosphoranes: a class of cyclic push-pull carbenes. AB - The synthesis of a novel family of cyclic push-pull carbenes, namely, azavinylidene phosphoranes, is described. The methodology is based on a formal [3+2] cycloaddition between terminal alkynes and phosphine-imines followed by an oxidation/deprotonation step. Carbenes 6, obtained by simple deprotonation, exhibit typical transient carbene reactivity like the intramolecular C?H insertion reaction and a pronounced ambiphilic character exemplified by [2+1] cycloaddition with electron-poor methyl acrylate. Owing to the cyclic structure, carbenes 6 also exhibit an excellent coordination ability toward transition metals. Rh(I) complex 10 was obtained in excellent yield and was fully characterized by multinuclear NMR spectroscopy and X-ray crystallography. The corresponding Rh(I) -carbonyl complex was also prepared; this indicates that carbenes 6 belong to the strongest sigma-donating ligands to date. DFT calculations confirmed the high sigma-donation ability of 6 and their classification as push-pull carbenes with a relatively small singlet-triplet energy gap of 23.2-24.3 kcal mol(-1) . PMID- 25123090 TI - [The posterocentral approach to the posterior tibial plateau]. AB - OBJECTIVE: An anatomically preformed approach to the posterior tibial plateau is described. In avulsion fractures of the posterior cruciate ligament (PCL), the aim is to restore stability of the knee joint with functional treatment, while in posterior shearing tibial plateau fractures the aim is to restore anatomical dorsal alignment of the tibia. INDICATIONS: Avulsion fracture the PCL, posterior shearing tibial plateau fracture. CONTRAINDICATIONS: Knee infection, compartment syndrome, joint instability, and osteoarthritis in avulsion fractures of the PCL. OPERATION TECHNIQUE: Supine position, L-shaped skin incision, dissection of the fascia, protection of the sural nerve, separation of the gastrocnemial heads, identification of the neurovascular bundle, retraction of the gastrocnemial heads. Fixation of the bony avulsion using screws. In tibial plateau fractures, dissection of the soleus and popliteus muscle, fracture reduction, and plate fixation. POSTOPERATIVE MANAGEMENT: Due to the approach no specific treatment necessary. PCL: functional treatment, with knee brace full weight bearing possible, without 20 kg weight bearing using crutches for 4-6 weeks, tibia: CT for postoperative result and planning of the ventral osteosynthesis after about 5 days, then weight bearing 20 kg and functional treatment for 8-12 weeks. RESULTS: A total of 33 patients were operated using a posterocentral approach, 22 had a posterior shearing tibial plateau fracture, and 11 an avulsion fracture of the PCL. Temporary hypesthesia around the scar, at the lateral foot, and lateral lower leg were observed in 3 patients, each having one (area supplied by the sural nerve). In 3 cases screw tips at the anterior proximal tibia were palpable. The posterocentral approach reveals a low complication rate due to the anatomical approach. PMID- 25123089 TI - Dye-loaded ferritin nanocages for multimodal imaging and photothermal therapy. AB - Multimodal imaging-guided photothermal therapy (PTT), for the therapy of cancer, based on a ferritin (FRT) nanocage loaded with the near-infrared dye IR820 (designated DFRT) is demonstrated. The dual roles of DFRT (in imaging and PTT) are successfully balanced by using two different excitation wavelengths: 550 nm for high quantum-yield fluorescence imaging on the one hand and 808 nm for photoacoustic imaging and PTT with high photothermal conversion efficiency on the other. PMID- 25123092 TI - A specialized post anaesthetic care unit improves fast-track management in cardiac surgery: a prospective randomized trial. AB - INTRODUCTION: Fast-track treatment in cardiac surgery has become the global standard of care. We compared the efficacy and safety of a specialised post anaesthetic care unit (PACU) to a conventional intensive care unit (ICU) in achieving defined fast-track end-points in adult patients after elective cardiac surgery. METHODS: In a prospective, single blinded, randomized study, 200 adult patients undergoing elective cardiac surgery (coronary artery bypass graft (CABG), valve surgery or combined CABG and valve surgery), were selected to receive their postoperative treatment either in the ICU (n = 100), or in the PACU (n = 100). Patients who, at the time of surgery, were in cardiogenic shock, required renal dialysis, or had an additive EuroSCORE of more than 10 were excluded from the study. The primary end points were: time to extubation (ET), and length of stay in the PACU or ICU (PACU/ICU LOS respectively). Secondary end points analysed were the incidences of: surgical re-exploration, development of haemothorax, new onset cardiac arrhythmia, low cardiac output syndrome, need for cardio-pulmonary resuscitation, stroke, acute renal failure, and death. RESULTS: Median time to extubation was 90 [50; 140] min in the PACU vs. 478 [305; 643] min in the ICU group (P < 0.001). Median length of stay in PACU was 3.3 [2.7; 4.0] hours vs. 17.9 [10.3; 24.9] hours in the ICU (P < 0.001). Of the adverse events examined, only the incidence of new onset cardiac arrhythmia (25 in PACU vs. 41 in ICU, P = 0.02) was statistically different between groups. CONCLUSIONS: Treatment in a specialised PACU rather than an ICU, after elective cardiac surgery leads to earlier extubation and quicker discharge to a step down unit, without compromising patient safety. TRIAL REGISTRATION: ISRCTN71768341. Registered 11 March 2014. PMID- 25123095 TI - Asymmetric Michael addition/intramolecular cyclization catalyzed by bifunctional tertiary amine-squaramides: construction of chiral 2-amino-4H-chromene-3 carbonitrile derivatives. AB - The efficient asymmetric Michael addition/intramolecular cyclization of malononitrile with dienones catalyzed by a chiral bifunctional tertiary amine squaramide catalyst for the synthesis of chiral 2-amino-4H-chromene-3 carbonitrile derivatives was developed. The corresponding products were obtained in good to excellent yields (up to 99%) with excellent enantioselectivities (up to 98% ee) for most of the bisarylidenecyclopentanones. PMID- 25123096 TI - Transport phenomena in nanoporous materials. AB - Diffusion, that is, the irregular movement of atoms and molecules, is a universal phenomenon of mass transfer occurring in all states of matter. It is of equal importance for fundamental research and technological applications. The present review deals with the challenges of the reliable observation of these phenomena in nanoporous materials. Starting with a survey of the different variants of diffusion measurement, it highlights the potentials of "microscopic" techniques, notably the pulsed field gradient (PFG) technique of NMR and the techniques of microimaging by interference microscopy (IFM) and IR microscopy (IRM). Considering ensembles of guest molecules, these techniques are able to directly record mass transfer phenomena over distances of typically micrometers. Their concerted application has given rise to the clarification of long-standing discrepancies, notably between microscopic equilibrium and macroscopic non equilibrium measurements, and to a wealth of new information about molecular transport under confinement, hitherto often inaccessible and sometimes even unimaginable. PMID- 25123093 TI - Shedding of Salmonella in single age caged commercial layer flock at an early stage of lay. AB - The shedding of Salmonella in a single age commercial egg layer flock was investigated at the onset of lay (18weeks) followed by two longitudinal samplings at 24 and 30weeks. At the age of 18weeks, when the first sampling was performed, the prevalence of Salmonella in faeces was 82.14% whereas all egg belt and dust samples were Salmonella positive by culture method. In later samplings, at the age of 24 and 30weeks, the prevalence of Salmonella in faeces was significantly reduced (p<0.001) to 38.88% and 12.95% respectively, however all egg belt and dust samples remained positive by culture method. The prevalence of Salmonella in faeces collected from the low tier cages was significantly higher (p=0.009) as compared with samples from the high tier cages. In all types of samples processed by culture method, S. Mbandaka was the most frequently (54.40%) isolated serovar followed by S. Worthington (37.60%), S. Anatum (0.8%), and S. Infantis (0.8%). All samples were also tested by real-time PCR method. The observed agreement between culture method and real-time PCR in detecting Salmonella-positive dust and egg belt samples was 100%. There was almost perfect agreement (observed agreement=99.21%) for the detection of Salmonella-positive eggshells. Observed agreement between culture method and real-time PCR for detecting Salmonella positive shoe cover and faecal samples was, however, moderate (80%) and low (54.27%) respectively. Real-time PCR results showed that there was a significant increase in the load of Salmonella on egg belt, dust and shoe cover samples at the 24 and 30weeks of lay as compared to the 18weeks of lay. Real-time PCR provided a more rapid and reliable method of detection of Salmonella on all dry sample types whereas the traditional culture method proved much more reliable when trying to detect Salmonella in wet faecal samples. PMID- 25123094 TI - Modeling of topology-dependent neural network plasticity induced by activity dependent electrical stimulation. AB - Activity-dependent electrical stimulation can induce cerebrocortical reorganization in vivo by activating brain areas using stimulation derived from the statistics of neural or muscular activity. Due to the nature of synaptic plasticity, network topology is likely to influence the effectiveness of this type of neuromodulation, yet its effect under different network topologies is unclear. To address this issue, we simulated small-scale three-neuron networks to explore topology-dependent network plasticity. The induced neuroplastic changes were evaluated by network coherence and unit-pair mutual information measures. We demonstrated that involvement of monosynaptic feedforward and reciprocal connections is more likely to lead to persistent decreased network coherence and increased network mutual information independent of the global network topology. On the contrary, disynaptic feedforward connections exhibit heterogeneous coherence and unit-pair mutual information sensitivity that depends strongly upon the network context. PMID- 25123097 TI - Allelic-specific expression in relation to Bombyx mori resistance to Bt toxin. AB - Understanding the mechanism of Bt resistance is one of the key elements of the effective application of Bt in pest control. The lepidopteran model insect, the silkworm, demonstrates qualities that make it an ideal species to use in achieving this understanding. We screened 45 strains of silkworm (Bombyx mori) using a Cry1Ab toxin variant. The sensitivity levels of the strains varied over a wide range. A resistant strain (P50) and a phylogenetically related susceptible strain (Dazao) were selected to profile the expressions of 12 Bt resistance related genes. The SNPs in these genes were detected based on EST analysis and were validated by allelic-specific PCR. A comparison of allelic-specific expression between P50 and Dazao showed that the transcript levels of heterozygous genes containing two alleles rather than an imbalanced allelic expression contribute more to the resistance of P50 against Bt. The responses of the allelic-specific expression to Bt in hybrid larvae were then investigated. The results showed that the gene expression pattern of an ATP-binding cassette transporter C2 (ABCC2) and an aminopeptidase N (APN3), changed in an allelic specific manner, with the increase of the resistant allele expression correlated with larval survival. The results suggest that a trans-regulatory mechanism in ABCC2 and APN3 allelic-specific expression is involved in the insect's response to the Bt toxin. The potential role of allelic-specific gene regulation in insect resistance to Bt toxins is discussed. PMID- 25123099 TI - Lanthanide doped nanoparticles as remote sensors for magnetic fields. AB - We report the effect of magnetic fields (MFs) on emission Eu-doped NaYF4 nanoparticles. A notable shift in the position of emission bands and the suppressed emission intensity are observed with the MF. These magnetic-optical interactions are explained in terms of the Zeeman effect, enhanced cross relaxation rate and change of site symmetry. PMID- 25123098 TI - [Symptom control and place of death in palliative cancer patients in primary care. Results of the controlled PAMINO evaluation study]. AB - BACKGROUND: The care of patients at the end of life focuses on preservation of the quality of life, symptom control and fulfillment of the preferred place of death. Only few care and outcome-related data for primary palliative care in Germany are available; therefore, the objective was to examine the quality of life, symptom control and place of death of patients with palliative treatment by general practitioners (GP). MATERIAL AND METHODS: The study is part of the PAMINO project, a non-randomized, controlled trial evaluating the effectiveness of continuing medical education for GPs (>= 40 h) in palliative care (ISRCTN78021852). Cancer patients with an estimated life expectancy of less than 6 months were recruited by GPs with (PG) or without (CG) continuing education and documented the diagnosis, medication based on the hospice and palliative care collation ( Hospiz- und Palliativ-Erfassung, HOPE) core documentation and the preferred place of death. Patients rated their symptom burden and health-related quality of life using the quality of life questionnaire (QLQ-C15-PAL). Baseline (t0) data at enrollment and the last individual (t1) assessment were used for the analysis. RESULTS: Data of 68 patients (PG: n = 43, CG: n = 25, mean age 69.2 +/- 12 years, average time since cancer diagnosis 14 months) were available at t0 and t1 (mean period 4.0 +/- 2.1 months). Physical function decreased while emotional functioning remained stable. Patient-perceived pain did not increase; however, GPs intensified the pain therapy. The PGs prescribed non-opioid analgesics more frequently than CGs. During the observation period 59 patients died of which 40 out of 48 (83 %) as preferred at home. CONCLUSIONS: Stable emotional functioning, good symptom control in cancer patients at the end of life and the high rate of dying at home as preferred suggest that GPs with specific training can ensure high-quality general palliative care. PMID- 25123100 TI - Median and quantile tests under complex survey design using SAS and R. AB - Techniques for conducting hypothesis testing on the median and other quantiles of two or more subgroups under complex survey design are limited. In this paper, we introduce programs in both SAS and R to perform such a test. A detailed illustration of the computations, macro variable definitions, input and output for the SAS and R programs are also included in the text. Urinary iodine data from National Health and Nutrition Examination Survey (NHANES) are used as examples for comparing medians between females and males as well as comparing the 75th percentiles among three salt consumption groups. PMID- 25123101 TI - Event-driven, pattern-based methodology for cost-effective development of standardized personal health devices. AB - Experiences applying standards in personal health devices (PHDs) show an inherent trade-off between interoperability and costs (in terms of processing load and development time). Therefore, reducing hardware and software costs as well as time-to-market is crucial for standards adoption. The ISO/IEEE11073 PHD family of standards (also referred to as X73PHD) provides interoperable communication between PHDs and aggregators. Nevertheless, the responsibility of achieving inexpensive implementations of X73PHD in limited resource microcontrollers falls directly on the developer. Hence, the authors previously presented a methodology based on patterns to implement X73-compliant PHDs into devices with low-voltage low-power constraints. That version was based on multitasking, which required additional features and resources. This paper therefore presents an event-driven evolution of the patterns-based methodology for cost-effective development of standardized PHDs. The results of comparing between the two versions showed that the mean values of decrease in memory consumption and cycles of latency are 11.59% and 45.95%, respectively. In addition, several enhancements in terms of cost-effectiveness and development time can be derived from the new version of the methodology. Therefore, the new approach could help in producing cost effective X73-compliant PHDs, which in turn could foster the adoption of standards. PMID- 25123102 TI - Bayesian bivariate generalized Lindley model for survival data with a cure fraction. AB - The cure fraction models have been widely used to analyze survival data in which a proportion of the individuals is not susceptible to the event of interest. In this article, we introduce a bivariate model for survival data with a cure fraction based on the three-parameter generalized Lindley distribution. The joint distribution of the survival times is obtained by using copula functions. We consider three types of copula function models, the Farlie-Gumbel-Morgenstern (FGM), Clayton and Gumbel-Barnett copulas. The model is implemented under a Bayesian framework, where the parameter estimation is based on Markov Chain Monte Carlo (MCMC) techniques. To illustrate the utility of the model, we consider an application to a real data set related to an invasive cervical cancer study. PMID- 25123103 TI - Geometric and electronic properties of edge-decorated graphene nanoribbons. AB - Edge-decorated graphene nanoribbons are investigated with the density functional theory; they reveal three stable geometric structures. The first type is a tubular structure formed by the covalent bonds of decorating boron or nitrogen atoms. The second one consists of curved nanoribbons created by the dipole-dipole interactions between two edges when decorated with Be, Mg, or Al atoms. The final structure is a flat nanoribbon produced due to the repulsive force between two edges; most decorated structures belong to this type. Various decorating atoms, different curvature angles, and the zigzag edge structure are reflected in the electronic properties, magnetic properties, and bonding configurations. Most of the resulting structures are conductors with relatively high free carrier densities, whereas a few are semiconductors due to the zigzag-edge-induced anti ferromagnetism. PMID- 25123104 TI - Platelet-to-lymphocyte ratio for early diagnosis of celiac disease. PMID- 25123106 TI - Tetralogy of Fallot with coronary artery to pulmonary artery fistula. PMID- 25123108 TI - Cricothyroid onabotulinum toxin A injection to avert tracheostomy in bilateral vocal fold paralysis. AB - IMPORTANCE: More than half of children with bilateral vocal fold paralysis require a tracheostomy for airway management. We report an innovative, minimally invasive approach consisting of onabotulinum toxin A injection into the cricothyroid muscles. OBSERVATIONS: Onabotulinum toxin A was injected under direct vision into the cricothyroid muscles of 6 pediatric patients with bilateral abductor vocal fold paralysis. None of the patients had fold fixation on laryngoscopy performed at the time of the injection. All patients had a documented increase in airway patency as visualized on flexible laryngoscopy within days after injection. This procedure successfully averted a tracheostomy in 5 patients and permitted decannulation of the sixth patient. CONCLUSIONS AND RELEVANCE: Onabotulinum toxin A injection into the cricothyroid muscles leads to an increase in the glottic space, providing an adequate airway. Onabotulinum toxin A injection in the cricothyroid muscles could be offered as a safe, effective, noninvasive first-line option for patients with bilateral vocal fold paralysis. PMID- 25123105 TI - Mice selected for extremes in stress reactivity reveal key endophenotypes of major depression: a translational approach. AB - Clear evidence has linked dysregulated hypothalamus-pituitary-adrenocortical (HPA) axis function to the aetiology and pathophysiology of major depression (MD), as observed in the majority of patients. Increased stress reactivity and hyperactivity of the HPA axis seem characteristic for psychotic/melancholic depression, while the atypical subtype of depression has been connected with the opposing phenotypes. However, the underlying molecular-genetic mechanisms are poorly understood. In the present study, mouse lines selectively bred for extremes in stress reactivity (SR), i.e. presenting high (HR) or low (LR) corticosterone secretion in response to stressors, were used to characterise the molecular alterations on all levels of the HPA axis. Results were contrasted with clinical phenotypes of MD patients from the Munich Antidepressant Response Signature project, stratified according to their cortisol response in the Dex/CRH test. Distinct differences between HR and LR mice were found in the expression of HPA axis-related genes in the adrenals, pituitary and selected brain areas. Moreover, HR animals presented an enhanced adrenal sensitivity, increased stress induced neuronal activation in the PVN and an overshooting Dex/CRH test response, whereas LR animals showed a blunted response in these paradigms. Interestingly, analogous neuroendocrine, morphometric, psychopathological and behavioural differences were observed between the respective high and low HPA axis responder groups of MD patients. Our findings suggests that (i) the SR mouse model can serve as a valuable tool to elucidate HPA axis-related mechanisms underlying affective disorders and (ii) a stratification of MD patients according to their HPA axis-related neuroendocrine function should be considered for clinical research and treatment. PMID- 25123107 TI - Risk and information evaluation of prioritized genes for complex traits: application to bipolar disorder. AB - Many susceptibility genes for complex traits were identified without conclusive findings. There is a strong need to integrate rapidly accumulated genomic data from multi-dimensional platforms, and to conduct risk evaluation for potential therapeutic and diagnostic usages. We set up an algorithm to computationally search for optimal weight-vector for various data sources, while minimized potential noises. Through gene-prioritization framework, combined scores for the resulting prioritized gene-set were calculated using a genome-wide association (GWA) dataset, following with evaluation using weighted genetic risk score and risk-attributed information using an independent GWA dataset. The significance of association of GWA data was corrected for gene length. Enriched functional pathways were identified for the prioritized gene-set using the Gene Ontology analysis. We illustrated our framework with bipolar disorder. 233 prioritized genes were identified from 10,830 candidates that curated from six platforms. The prioritized genes were significantly enriched (P(adjusted) < 1 * 10(-5)) in 18 biological functions and molecular mechanisms including membrane, synaptic transmission, transmission of nerve impulse, integral to membrane, and plasma membrane. Our risk evaluation demonstrated higher weighted genetic risk score in bipolar patients than controls (P-values ranged from 0.002 to 3.8 * 10(-6)). Substantial risk-information (71%) was extracted from prioritized genes for bipolar illness than other candidate-gene sets. Our evidence-based prioritized gene-set provides opportunity to explore the complex network and to conduct follow-up basic and clinical studies for complex traits. PMID- 25123109 TI - Reversible Pisa syndrome associated to subdural haematoma: case-report. AB - BACKGROUND: Pisa Syndrome or Pleurothotonus is a relatively rare truncal dystonia, characterized by tonic flexion of the trunk and head to one side with slight rotation of the body. Since frequently associated to specific drugs such as antipsychotics and cholinesterase inhibitors or to Parkinson Disease, a pathophysiological role of cholinergic-dopaminergic imbalance has been suggested. We report here the first case of Pisa Syndrome due to an extracerebral pathology as subdural haematoma. CASE PRESENTATION: A hypertensive patient was admitted to Our Department for subacute onset of tonic flexion and slight rotation of the trunk associated to progressive motor deficit in left upper limb after a mild head trauma without loss of consciousness occurred around three month before. No previous or current pharmacological interventions with antidepressant, neuroleptic or anticholinergic drugs were anamnestically retrieved. Familiar and personal history was negative for neurological disorders other than acute cerebrovascular diseases. Acutely performed cerebral MRI with DWI showed a voluminous right subdural haematoma with mild shift of median line. After surgical evacuation, both motor deficit and truncal dystonia were dramatically resolved. At one-year follow up, the patient did not develop any extrapyramidal and cognitive signs or symptoms. CONCLUSIONS: According to many Authors, the occurrence of truncal dystonia during several pharmacologic treatments and neurodegenerative disorders (such as Alzheimer disease and parkinsonian syndromes) supported the hypothesis that a complex dysregulation of multiple neurotransmitter systems are involved. We suggest a possible role of basal ganglia compression in pathogenesis of truncal dystonia by means of thalamo cortical trait functional disruption and loss of proprioceptive integration. A further contribution of the subcortical structure displacement that alters motor cortex connectivity to basal ganglia may be postulated. PMID- 25123111 TI - "Neuroendocrine adenoma of the middle ear with the history of otitis media and carcinoma of the cheek: a case report". AB - BACKGROUND: Neuroendocrine adenomas of the middle ear are rare benign tumors deriving from middle ear mucosal cell with both neuroendocrine and epithelial properties. Approximately one hundred cases have been reported in the literature. Here we report a patient with neuroendocrine adenoma of the middle ear with the history of otitis media; the patient earlier had received radiotherapy for the treatment of basal cell carcinoma. CASE PRESENTATION: A 49- year- old Saudi man presented with a progressive hearing loss and fullness in the left ear with the history of otitis media for which he had undergone myringotomy and ventilating tubes insertion. Earlier at the age of 45 years this patient was given radiotherapy for the treatment of basal cell carcinoma in his cheek. The otoscopy showed a protruded external ear mass obscuring the tympanic membrane. Microscopy and histological examination suggested an endocrine adenoma of the middle ear. The computerized tomography scan of the temporal bone showed an extensive soft tissue mass without any osteolysis. Histological and immunohistochemical examination following surgical excision confirmed the diagnosis of neuroendocrine adenoma of the middle ear. CONCLUSION: A rare case of neuroendocrine adenoma of the middle ear with earlier history of otitis media and carcinoma of the cheek is presented here. Surgical excision of mass resulted in uneventful recovery. Although the etiologic factors leading to the disease is far from clear, the role of radiotherapy given for the treatment of basal cell carcinoma may not be ruled out. PMID- 25123110 TI - Functional outcome in people at high risk for psychosis predicted by thalamic glutamate levels and prefronto-striatal activation. AB - Little is known about the neurobiological factors that determine functional outcome in people at high risk for psychosis. We use multimodal neuroimaging to investigate whether cortical responses during a cognitive task and thalamic glutamate levels were associated with subsequent functional outcome. Sixty subjects participated: 27 healthy controls (CTRL) and 33 at ultrahigh risk (UHR) for psychosis. At baseline, cortical responses during a verbal fluency task were measured using functional Magnetic Resonance Imaging (fMRI) and proton Magnetic Resonance Spectroscopy (1H-MRS) was used to measure thalamic glutamate levels. The UHR subjects were then followed clinically for a mean duration of 18 months, and subdivided into "good" and "poor" functional outcome subgroups according to their Global Assessment of Function score at follow-up. UHR subjects with a poor functional outcome showed greater cortical and subcortical activation than UHR subjects with a good functional outcome. They also had lower levels of thalamic glutamate and showed a negative relationship between thalamic glutamate levels and prefrontal-striatal activation that was not present in the good functional outcome or control groups. In people at high risk for psychosis, their subsequent level of functioning may depend on the extent to which neurophysiological and neurochemical function is perturbed when they first present to clinical services. PMID- 25123112 TI - An eight-year epidemiologic study based on baculovirus-expressed type-specific spike proteins for the differentiation of type I and II feline coronavirus infections. AB - BACKGROUND: Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV). FCoVs are divided into two serotypes with markedly different infection rates among cat populations around the world. A baculovirus expressed type-specific domain of the spike proteins of FCoV was used to survey the infection of the two viruses over the past eight years in Taiwan. RESULTS: An immunofluorescence assay based on cells infected with the recombinant viruses that was capable of distinguishing between the two types of viral infection was established. A total of 833 cases from a teaching hospital was surveyed for prevalence of different FCoV infections. Infection of the type I FCoV was dominant, with a seropositive rate of 70.4%, whereas 3.5% of cats were infected with the type II FCoV. In most cases, results derived from serotyping and genotyping were highly agreeable. However, 16.7% (4/24) FIP cats and 9.8% (6/61) clinically healthy cats were found to possess antibodies against both viruses. Moreover, most of the cats (84.6%, 22/26) infected with a genotypic untypable virus bearing a type I FCoV antibody. CONCLUSION: A relatively simple serotyping method to distinguish between two types of FCoV infection was developed. Based on this method, two types of FCoV infection in Taiwan was first carried out. Type I FCoV was found to be predominant compared with type II virus. Results derived from serotyping and genotyping support our current understanding of evolution of disease-related FCoV and transmission of FIP. PMID- 25123113 TI - Characterization of newly gained introns in Daphnia populations. AB - As one of the few known species in an active phase of intron proliferation, the microcrustacean Daphnia pulex is an especially attractive system for interrogating the gain and loss of introns in natural populations. In this study, we used a comparative population-genomic approach to identify and characterize 90 recently gained introns in this species. Molecular clock analyses indicate that these introns arose between 3.9 * 10(5) and 1.45 * 10(4) years ago, with a spike in intron proliferation approximately 5.2 * 10(4) to 1.22 * 10(5) years ago. Parallel gains at homologous positions contribute to 47.8% (43/90) of discovered new introns. A disproportionally large number of new introns were found in historically isolated populations in Oregon. Nonetheless, derived, intron-bearing alleles were also identified in a wide range of geographic locations, suggesting intron gain and, to a lesser degree, intron loss are important sources of genetic variation in natural populations of Daphnia. A majority (55/90 or 61.1%) of the identified neointrons have associated internal direct repeats with lengths and compositions that are unlikely to occur by chance, suggesting repeated bouts of staggered double-strand breaks (DSBs) during their evolution. Accordingly, internal, staggered DSBs may contribute to a passive trend toward increased length and sequence diversity in nascent introns. PMID- 25123115 TI - "We are supposed to take care of it": a qualitative examination of care and repair behaviour of long-lasting, insecticide-treated nets in Nasarawa State, Nigeria. AB - BACKGROUND: The longevity of long-lasting insecticidal nets (LLIN) under field conditions has important implications for malaria vector control. The behaviour of bed net users, including net care and repair, may protect or damage bed nets and impact the physical integrity of nets. However, this behaviour, and the motivating and inhibiting factors, is not well understood. METHODS: Qualitative research methods were used to examine behaviour, attitudes and norms around damage, care and repair of LLINs. Eighteen in-depth interviews (IDI) and six focus group discussions (FGD) were conducted with LLIN users in two local government areas of Nasarawa State, Nigeria. A brief background questionnaire with the 73 participants prior to IDIs or FGDs collected additional data on demographics, net use, and care and repair behaviour. RESULTS: Respondents cited that the major causes of damage to bed nets are primarily children, followed by rodents, everyday handling that is not gentle, and characteristics of sleeping spaces. Caring for nets was perceived as both preventing damage by careful handling and keeping the net clean, which may lead to over-washing of LLINs. Repairing a damaged net was considered something that net users should do and the responsibility of adults in the household. Despite this, reported frequency of net repair was low (18%). Motivations for taking care of and repairing nets centred around caring for one's family, avoiding mosquito bites, saving money, and maintaining the positive opinion of others by keeping a clean and intact net. Barriers to net care and repair related to time availability and low perceived value of bed nets or of one's health. CONCLUSION: This study provides novel and valuable insights on the perceptions and attitudes of LLIN users in Nasarawa, Nigeria on the durability of bed nets, how to care for and repair nets, and for what reasons. Communication around net care should stress proper daily storage of nets, regular net inspections, prompt repairs, and clarify misconceptions about proper washing frequency and technique. These messages should include compelling motivators, such as local social norms of household hygiene. PMID- 25123114 TI - The transcriptome of Nacobbus aberrans reveals insights into the evolution of sedentary endoparasitism in plant-parasitic nematodes. AB - Within the phylum Nematoda, plant-parasitism is hypothesized to have arisen independently on at least four occasions. The most economically damaging plant parasitic nematode species, and consequently the most widely studied, are those that feed as they migrate destructively through host roots causing necrotic lesions (migratory endoparasites) and those that modify host root tissue to create a nutrient sink from which they feed (sedentary endoparasites). The false root-knot nematode Nacobbus aberrans is the only known species to have both migratory endoparasitic and sedentary endoparasitic stages within its life cycle. Moreover, its sedentary stage appears to have characteristics of both the root knot and the cyst nematodes. We present the first large-scale genetic resource of any false-root knot nematode species. We use RNAseq to describe relative abundance changes in all expressed genes across the life cycle to provide interesting insights into the biology of this nematode as it transitions between modes of parasitism. A multigene phylogenetic analysis of N. aberrans with respect to plant-parasitic nematodes of all groups confirms its proximity to both cyst and root-knot nematodes. We present a transcriptome-wide analysis of both lateral gene transfer events and the effector complement. Comparing parasitism genes of typical root-knot and cyst nematodes to those of N. aberrans has revealed interesting similarities. Importantly, genes that were believed to be either cyst nematode, or root-knot nematode, "specific" have both been identified in N. aberrans. Our results provide insights into the characteristics of a common ancestor and the evolution of sedentary endoparasitism of plants by nematodes. PMID- 25123117 TI - Predictors of long-term effect from education and exercise in patients with knee and hip pain. AB - INTRODUCTION: Education and exercise are poorly implemented in osteoarthritis care. The purpose of the present study was to identify predictors of effectiveness at one year from education and exercise in patients with knee or hip pain in clinical practice. MATERIAL AND METHODS: Good Life with Arthritis in Denmark is an implementation initiative consisting of education and 12 sessions of neuromuscular exercise delivered by trained physiotherapists. Pain (visual analogue scale 0-100) and quality of life (EQ-5D) were assessed at baseline and after three and 12 months. Changes in outcome from baseline to one year were dependent variables in regression analyses, while changes from baseline to 3 months and absolute results at three months in physical performance (30-second chair stand test) and self-efficacy were predictor variables. RESULTS: A total of 79/82 patients completed the one-year follow-up. Improvements in pain and EQ-5D at three months were maintained at one year (p < 0.006). Change in self-efficacy from baseline to three months (Beta = -0.369) and 30-second chair stand test (Beta = -0.251) and self-efficacy at three months (Beta = -0.492) were predictors of one-year improvement in pain (p < 0.05). Furthermore, self-efficacy at three months (Beta = 0.304) was a predictor of one-year improvement in EQ-5D (p = 0.01). CONCLUSION: The identified predictors highlight the importance of combining education and exercise. This study indicates that good long-term treatment results are achievable in clinical practice. PMID- 25123116 TI - Could hyaluronic acid (HA) reduce Bacillus Calmette-Guerin (BCG) local side effects? Results of a pilot study. AB - BACKGROUND: Bacillus Calmette-Guerin (BCG) is considered the most effective treatment to reduce recurrence and progression of non-muscle invasive bladder cancer (NMIBC) but can induce local side effects leading to treatment discontinuation or interruption. Aim of this exploratory study is to investigate if the sequential administration of Hyaluronic acid (HA) may reduce local side effects of BCG. METHODS: 30 consecutive subjects undergoing BCG intravesical administration for high risk NMIBC were randomized to receive BCG only (Group A) or BCG and HA (Group B). A 1 to 10 Visual Analog Scale (VAS) for bladder pain, International Prostate Symptom Score (IPSS) and number of micturitions per day were evaluated in the two groups before and after six weekly BCG instillations. Patients were also evaluated at 3 and 6 months by means of cystostopy and urine cytology. RESULTS: One out of 30 (3,3%) patients in group A dropped out from the protocol, for local side effects. Mean VAS for pain was significantly lower in group B after BCG treatment (4.2 vs. 5.8, p = 0.04). Post vs. pre treatment differences in VAS for pain, IPSS and number of daily micturitions were all significantly lower in group B. Three patients in group A and 4 in group B presented with recurrent pathology at 6 month follow up. CONCLUSIONS: These preliminary data suggest a possible role of HA in reducing BCG local side effects and could be used to design larger randomized controlled trials, assessing safety and efficacy of sequential BCG and HA administration. TRIAL REGISTRATION: NCT02207608 (ClinicalTrials.gov) 01/08/2014. Policlinico Tor Vergata Ethics Committee, resolution n 69-2011. PMID- 25123118 TI - Admission medical records made at night time have the same quality as day and evening time records. AB - INTRODUCTION: A thorough and accurate admission medical record is an important tool in ensuring patient safety during the hospital stay. Surgeons' performance might be affected during night shifts due to sleep deprivation. The aim of the study was to assess the quality of admission medical records during day, evening and night time. MATERIAL AND METHODS: A total of 1,000 admission medical records were collected from 2009 to 2013 based equally on four diagnoses: mechanical bowel obstruction, appendicitis, gallstone disease and gastrointestinal bleeding. The records were reviewed for errors by a pre-defined checklist based on Danish standards for admission medical records. The time of dictation for the medical record was registered. RESULTS: A total of 1,183 errors were found in 778 admission medical records made during day- and evening time, and 322 errors in 222 admission medical records from night time shifts. No significant overall difference in error was found in the admission medical records when day and evening values were compared to night values. Subgroup analyses made for all four diagnoses showed no difference in day and evening values compared with night time values. CONCLUSION: Night time deterioration was not seen in the quality of the medical records. PMID- 25123119 TI - Treatment of insufficient lactation is often not evidence-based. AB - INTRODUCTION: Breast milk has many advantages over formula for infants in developed and developing countries alike. Despite intentions of breastfeeding, some women develop insufficient lactation. Treatment options traditionally include breastfeeding education and pharmacotherapy. MATERIAL AND METHODS: An electronic questionnaire regarding treatment of insufficient lactation was sent to all obstetric departments (n = 21) and neonatal wards (n = 17) in Denmark. Three main questions were included which focused on: breastfeeding education for women, use of pharmacotherapy and availability of local guidelines. RESULTS: In all, 30 out of a total of 38 departments participated; and among those, 93% offered some form of breastfeeding education. 50% used either metoclopramide or syntocinon to promote lactation. None used domperidone. 73% had a local clinical guideline. 77% offered sessions with a lactation consultant. CONCLUSION: Despite lack of evidence, half of the Danish obstetric departments and neonatal wards use metoclopramide and syntocinon for insufficient lactation. Domperidone might provide an alternative, but no departments reported its use. Management of insufficient lactation should always be initiated by counselling and education. Only when these treatment options are exhausted should pharmacotherapy with a suitable medication be considered. PMID- 25123120 TI - Improvement in health-related quality of life following Roux-en-Y gastric bypass. AB - INTRODUCTION: This study explored whether health-related quality of life (HRQOL) changes following Roux-en-Y gastric bypass surgery were associated with identifiable socio-demographic or clinical characteristics, and it examined the impact on health outcomes of changes in the Danish criteria for bariatric surgery. MATERIAL AND METHODS: Participants (n = 55) completed the Short Form Health Survey v2 (SF-36) before and 22 +/- 4.2 months after surgery. Information on socio-demographics, body mass index (BMI), co-morbidity and satisfaction with surgery were collected through patient questionnaires and hospital records. RESULTS: There was overall improvement on all SF-36 subscales and in the mean physical score (PCS) and mean mental score (MCS) (p = 0.001). A total of five patients had lower PCS and 13 patients had lower MCS after surgery, but we identified no particular characteristics associated with this poorer outcome. Co morbidity and preoperative PCS/MCS showed a strong correlation with change in PCS/MCS score. CONCLUSION: Gastric bypass had a positive overall effect on HRQOL, but further investigation of individual variations is needed. We found no significant differences in HRQOL outcome between those patients who would be accepted for bariatric surgery under the current Danish criteria for bariatric surgery and those patients who only fulfilled the criteria for bariatric surgery before 2011. FUNDING: not relevant. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02032199. PMID- 25123121 TI - Treatment of hypophosphataemic rickets in children remains a challenge. AB - INTRODUCTION: Hypophosphataemic rickets (HR) is a rare hereditary disease characterised by hypophosphataemia, defects in bone mineralisation and rickets. MATERIAL AND METHODS: We searched the hospital files at H.C. Andersen Children's Hospital, Odense University Hospital, Denmark, for children with the International Classification of Diseases 10 codes E83.3B (vitamin D resistant rickets) and E83.3A1 (familiar hypophosphataemia) from 1 February 2012 to 1 May 2012. Data were collected retrospectively. RESULTS: Fifteen HR children were identified. X-linked hypophosphataemia with mutations in the phosphate-regulating endopeptidase homologue, X-linked were present in 80%; three had autosomal recessive HR with dentin matrix protein mutations. The children were treated with phosphate and alphacalcidol for an average of 7.7 years +/- 5.1 standard deviations (SD). At the latest follow-up, the mean age was 10.1 (+5.4) years, and the mean height had declined 0.8 SD from the first contact. A total of 40% had an actual height below -2.0 SD, and 40% underwent surgery for leg deformities. Among the medically treated patients, five had genu varus with a mean medial femoral condyle distance of 6.6 cm (+ 2.79), and two patients had genu valgus with a mean medial malleolus distance of 12.3 cm (+ 1.77). Episodes of secondary hyperparathyroidism were seen in 87%, and one patient developed transient nephrocalcinosis. CONCLUSION: The current medical treatment for HR is insufficient. The rarity of the disease and the treatment difficulties of HR call for centralised management. International multi-centre trials including novel treatment options are warranted. PMID- 25123122 TI - Poor interpretation of chest X-rays by junior doctors. AB - INTRODUCTION: Studies targeting medical students and junior doctors have shown that their radiological skills are insufficient. Despite the widespread use of chest X-ray; however, a study of Danish junior doctors' skills has not previously been performed. MATERIAL AND METHODS: A total of 22 participants per-used a standardised series of ten chest X-rays. The test used a multiple-choice form for each image, and the clinical data and the tentative diagnosis of each image were also made available to the participants. For each image, the participant chose a single primary diagnosis; and for each diagnosis, the participant's confidence in the diagnosis was assessed on a five-point Likert scale. The diagnoses were divided into four groups: normal findings, chronic diseases, acute diseases and hyperacute diseases or conditions. RESULTS: A total of 22 doctors receiving basic clinical education (BCE) completed the study. Overall, participants correctly established 51% of the diagnoses. The participants' overall confidence in the primary diagnoses was 57.5% on the Likert scale, corresponding to 57.5% confidence in the proposed diagnoses. The sensitivity was calculated to 0.49 (95% confidence interval (CI): 0.41-0.57) and the specificity to 0.55 (95% CI: 0.41 0.68). CONCLUSION: Based on the results from this study, we conclude that BCE doctors do not meet the minimum requirements for radiological diagnostic skills for the use of chest X-ray that were established for this study. PMID- 25123123 TI - Increased mortality in the elderly after emergency abdominal surgery. AB - INTRODUCTION: The purpose of this study was to evaluate the relation between preoperative delay and mortality in surgical patients undergoing primary emergency laparotomy (PEL) in an unselected, well-described patient cohort in a university hospital setting. MATERIAL AND METHODS: This study was a retrospective analysis of patient charts and perioperative documentation in an unselected consecutive cohort of 131 patients. Covariates for survival outcomes were evaluated in a multivariate analysis. No external funding and no competing interests were declared. The study was approved by The Danish Data Protection Agency; and in pursuance of national Danish research guidelines concerning retrospective studies, approval from ethics committee was not relevant. RESULTS: PEL was performed in 131 patients in the observation period. The median age of the patients was 68 years. The median time from admission to start of operation for all patients was 9.5 hours. No association between a time to operation exceeding six hours and post-operative mortality was found (adjusted odds ratio (95% confidence interval) = 0.67 (0.25-1.78)). Patients over 75 years of age had a very high mortality (47.8%). Most patients died within 30 days post operatively. CONCLUSION: Acute admission and emergency laparotomy is associated with a very high mortality, especially in elderly patients. However, delay in the surgical treatment exceeding six hours is not associated with a higher mortality. There may be a considerable potential for improving care and management in these patients through a more systematic approach. PMID- 25123124 TI - Single-port laparoscopic rectal surgery - a systematic review. AB - INTRODUCTION: Single-port laparoscopic surgery (SPLS) for colonic disease has been widely described, whereas data for SPLS rectal resection are sparse. This review aimed to evaluate the feasibility, safety and complication profile of SPLS for rectal diseases. METHODS: A systematic literature search of PubMed and Embase was performed in September 2013 according to the PRISMA guidelines. Original reports on the use of SPLS in high and low anterior resection, Hartmann's operation and abdominoperineal resection were included. Outcome measures were intra-operative details and complications, short-term oncological outcome and early complication profile. RESULTS: No randomised studies or controlled clinical studies were identified. All studies were case series or case reports. Only five studies included more than ten patients operated with SPLS, comprising a total of 120 patients. These studies formed the basis for the final analyses of outcome. Operative times ranged from 79 to 280 min. Conversion rates to conventional laparoscopic surgery and to open surgery were 12% and 2.5%, respectively. The number of harvested lymph nodes in malignant cases was 13-18. The post-operative complication rate was 25.5%. Length of hospital stay was 1-16 days. No 30-day mortality was reported. CONCLUSION: Short-term results suggest that SPLS for rectal disease is feasible and safe with an acceptable complication rate when performed by experienced surgeons in selected patients. Oncological safety and the possible benefits remain to be proven. Future rectal SPLS procedures should be performed in a protocolled set-up. PMID- 25123125 TI - Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance. AB - Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients with type 2 diabetes. This supports the hypothesis of an unique pathogenesis of insulin resistance in PCOS. Insulin in physiological concentrations stimulates glucose uptake in human skeletal muscle in vivo by activation of the insulin signaling cascade to glucose transport through the enzymes IRS1, PI3K, Akt2, AS160/TBC1D4 and RAC1, and to glycogen synthesis through Akt2, inhibition of GSK3 and activation of glycogen synthase (GS) via dephosphorylation of serine residues in both the NH2-terminal (site 2+2a) and the COOH-terminal end (site 3a+3b). In type 2 diabetes, obesity and PCOS, there is, although with some variation from study to study, defects in insulin signaling through IRS1, PI3K, Akt2 and AS160/TBC1D4, which can explain reduced insulin action on glucose transport. In type 2 diabetes an altered intracellular distribution of SNAP23 and impaired activation of RAC1 also seem to play a role for reduced insulin action on glucose transport. In all common metabolic disorders, we observed an impaired insulin activation of GS, which seems to be caused by attenuated dephosphorylation of GS at site 2+2a, whereas as the inhibition of GSK3 and the dephosphorylation of GS at its target sites, site 3a+3a, appeared to be completely normal. In individuals with inherited insulin resistance, we observed largely the same defects in insulin action on IRS1, PI3K, Akt2 and GS, as well as a normal inhibition of GSK3 and dephosphorylation of GS at site 3a+3b. In these individuals, however, a markedly reduced insulin clearance seems to partially rescue insulin signaling to glucose transport and GS. Adiponectin is thought to improve insulin sensitivity primarily by increasing lipid oxidation through activation of the enzyme AMPK, and possibly via cross talking of adiponectin with insulin signaling, and hence glucose transport and glycogen synthesis. We demonstrated a strong correlation between plasma adiponectin and insulin action on glucose disposal and glycogen synthesis in obesity, type 2 diabetes and PCOS. In individuals with inherited insulin resistance, plasma adiponectin was normal, but the correlation of adiponectin with insulin-stimulated glucose uptake and glycogen synthesis was at least equally strong. Moreover, we found a correlation between plasma adiponectin and insulin activation of GS. This result is supported by a number of recent studies of animal models and muscle cell lines, which have shown that adiponectin augments insulin action on enzymes in the insulin signaling cascade. In contrast, we observed no differences in the abundance or activity of AMPK in obesity, type 2 diabetes, PCOS or inherited insulin resistance. This indicates that reduced insulin sensitivity in these conditions is not mediated via abnormal AMPK activity. The results from these studies demonstrate that the well-established abnormalities in insulin action on glucose uptake and glycogen synthesis are reflected by defects in insulin signaling to these cellular processes in type 2 diabetes, obesity, and PCOS, and as expected also in inherited insulin resistance caused by a mutation in INSR. In common metabolic disorders, low plasma adiponectin may contribute to insulin resistance and defects in insulin signaling, whereas in inherited insulin resistance a normal plasma adiponectin and reduced insulin clearance could contribute to maintain a sufficient activation of the insulin signaling cascade. The insight gained from these studies have improved our understanding of the molecular mechanisms underlying insulin resistance in skeletal muscle of humans, and can form the basis for further studies, which can lead to the development of treatment that more directly targets insulin resistance, and hence reduce the risk of type 2 diabetes and cardiovascular disease. PMID- 25123126 TI - Prognostic interactions between cardiovascular risk factors. AB - BACKGROUND: Cardiovascular disease (CVD) still remains the leading cause of death worldwide, especially in Europe where the prevalence of hypertension is 60% higher compared with the United States and Canada and the clustering of hypertension and the metabolic disorders central adiposity, dyslipidemia and dysglycemia, known as the metabolic syndrome (MetS), affects 25% of the population. Despite the great initiatives of many primary prevention strategies, risk factor control is still poor. In an attempt to optimize risk factor control, two issues among others have been of great debate in the past decade: (1) the superiority of systolic blood pressure (SBP) as a risk factor in the elderly; and (2) the clinical relevance of MetS. However, in order to further elucidate these issues, we need to get a deeper understanding of how the cardiovascular risk factors interact with one another. Thus, prognostic interactions were used in the present PhD thesis to test the following hypotheses: Primary hypotheses: (1) The superiority of SBP over diastolic blood pressure (DBP) as a risk factor occurs at an earlier age if an individual presents with other cardiovascular risk factors. (2) The prevalence and prognostic significance of MetS differ according to age and gender. The first hypothesis is explored in paper 1 (for the endpoint fatal and nonfatal (total) stroke) and paper II (for mortality from coronary heart disease (CHD), stroke, and all-causes), while the second hypothesis is explored in paper III (for total CHD, total stroke, and CVD mortality). METHODS: Using 34 42 cohorts from the MORGAM Project with baseline between 1982-1997, approximately 68 000-86 000 apparently healthy men and women aged 19-78 years, without CVD (papers I-III) and not receiving antihypertensive treatment (papers I-II) were included. During 12-13 years of follow-up, the incident events of total stroke were up to 1957, of total CHD were 4368, and of all-cause mortality were 7903. In papers I-II, event risk was analyzed by multivariate-adjusted Cox regressions including SBP and DBP simultaneously, as well as other cardiovascular risk factors and any significant interactions between variables. In paper III, MetS prevalence and prognostic significance was considered according to modified definitions of the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program - Adult Treatment Panel (NCEP-ATP III), and the influence of possible interactions between age and gender on MetS prevalence and prognostic significance was explored using logistic as well as multivariate-adjusted Cox regressions. MetS was analyzed separately for men and women in various age-groups. RESULTS: Taking into account the significant interactions between cardiovascular risk factors, the results were as follows: Papers I-II: Age-related shifts were shown for the independent relative importance of SBP and DBP as risk factors for stroke (both total and fatal) and all-cause mortality, but not for CHD mortality where SBP remained significant in all ages. The prognostic shift to the superiority of SBP was significantly established in the 6th decade, and only for stroke mortality was this shift influenced by other cardiovascular risk factors, such that it occurred at an earlier age in men from high-risk countries and with a higher cholesterol level. However, from mid-age and onwards, a potential harmful effect of low DBP for the risk of total stroke and all-cause mortality was present. Paper III: The prevalence and prognostic significance of MetS showed great variations among countries and were influenced by both age and gender. With older age, the prevalence of MetS increased 5-fold in women from ages 19-39 years to 60-78 years and 2-fold in men. The CVD risk associated with MetS was (1) higher in women than in men especially when using the NCEP-ATP III criteria, and (2) independently of age in men whereas in women total CHD risk decreased significantly and the total stroke risk tended to increase (although not significant) with older age. CONCLUSION: The present thesis elucidates through prognostic interactions the complex interplay between cardiovascular risk factors. Our results indicate the independent prognostic superiority of SBP in elderly Europeans, and only for stroke mortality risk this prognostic superiority of SBP was influenced by other cardiovascular risk factors such that it was established at an earlier age. The prevalence and prognostic significance of MetS differed according to both age and gender. In women, MetS was associated with higher relative event risks and the MetS associated relative CHD risk decreased with advancing age. PMID- 25123127 TI - Offspring body size and metabolic profile - effects of lifestyle intervention in obese pregnant women. AB - Worldwide, the prevalence of obesity has reached epidemic proportions. In Denmark one third of all pregnant women are overweight and 12 % are obese. Perhaps even more concerning, a dramatic rise in the prevalence of childhood overweight and obesity has also been evident over recent decades. The obesity epidemic is not simply a consequence of poor diet or sedentary lifestyles. Obesity is a multifactorial condition in which environmental, biological and genetic factors all play essential roles. The Developmental Origins of Health and Disease (DoHaD) hypothesis has highlighted the link between prenatal, perinatal and early postnatal exposure to certain environmental factors and subsequent development of obesity and non-communicable diseases. Maternal obesity and excessive gestational weight gain, resulting in over-nutrition of the fetus, are major contributors to obesity and metabolic disturbances in the offspring. Pregnancy offers the opportunity to modify the intrauterine environment, and maternal lifestyle changes during gestation may confer health benefits to the child. The overall aim with this PhD thesis was to study the effects of maternal obesity on offspring body size and metabolic outcomes, with special emphasis on the effects of lifestyle intervention during pregnancy. The thesis is based on a literature review, description of own studies and three original papers/manuscripts (I, II and III). In paper I, we used data from the Danish Medical Birth Registry. The aim of this paper was to examine the impact of maternal pregestational Body Mass Index (BMI) and smoking on neonatal abdominal circumference (AC) and weight at birth and to define reference curves for birth AC and weight in offspring of healthy, non-smoking, normal weight women. Data on 366,886 singletons were extracted and analyzed using multivariate linear regressions. We found that birth AC and weight increased with increasing pregestational BMI and decreased with smoking. Reference curves were created for offspring of healthy, non-smoking mothers with normal pregestational BMI. Paper II and III are based on an offspring follow-up of a randomized controlled trial (RCT) with 360 obese pregnant women. The intervention during pregnancy consisted of two major components: dietary advice and physical activity. The intervention resulted in a small, but significant difference in gestational weight gain compared to the control group. A number of 301 completed the trial and were eligible for the follow-up. We managed to include 157 mother and child dyads in the follow-up, which was conducted in Odense University Hospital and Aarhus University Hospital, Skejby between February 2010 and November 2012. At that time the children were in the ages 2.5-3 years. In addition to the children from the RCT, a group of 97 children born to lean mothers were included as an external reference group. The follow-up consisted of a clinical examination with anthropometric measures, DEXA scans and fasting blood samples for evaluation of metabolic outcomes. In paper II the effect of the maternal intervention on offspring body composition and anthropometric outcomes was studied. The primary outcome was BMI Z-score and secondary outcomes were: body composition values by DEXA (fat mass, lean mass and fat percentage), BMI, percentage of overweight or obese children and skin fold thicknesses. We found no significant differences in offspring outcomes between randomized groups of the preceding RCT. Neither was any differences detected between offspring of the RCT or the external reference group born to lean mothers. Paper III focused on the metabolic outcomes in the offspring. We additionally studied the predictive values of birth weight (BW) and birth abdominal circumference (BAC) on metabolic risk factors. We found that both BAC and BW were significantly associated with several risk factors in early childhood. All metabolic measurements in RCT offspring were similar, and no differences were detected between the RCT offspring and the external reference group of offspring of lean mothers. Lifestyle intervention in obese pregnant women has the potential to modify the intrauterine environment and confer long term benefits to the child. In this follow-up study, lifestyle intervention in pregnancy did not result in changes in offspring body composition or metabolic risk factors at 2.8 years. This might be due to a limited difference in gestational weight gain between follow-up attendees. When comparing offspring of obese women with offspring of normal weight mothers all outcomes were similar. We speculate that obese mothers entering a lifestyle intervention RCT regardless of the intervention have a high motivation to focus on healthy lifestyle during pregnancy, which makes it difficult to determine the effects of the randomized lifestyle intervention compared to an unselected control group of obese women. Our studies (paper I and III) on birth abdominal circumference show that abdominal size at birth is a good predictor of later adverse metabolic profile. Abdominal circumference at birth may reflect visceral adiposity and this measurement together with birth weight are strongly associated to later adverse metabolic outcome. Future studies should be performed in other populations to confirm this. PMID- 25123128 TI - Trophectoderm morphology predicts outcomes of pregnancy in vitrified-warmed single-blastocyst transfer cycle in a Chinese population. AB - PURPOSE: In this study, we estimated the effect of blastocoele expansion, ICM and TE quality after warming and culture on the rates of clinical pregnancy, live birth and miscarriage in vitrified-warmed single-blastocyst transfer cycle in a Chinese population. METHODS: A retrospective analysis of 263 cycles of vitrified warmed single-blastocyst transfers was performed. RESULTS: The blastocysts with higher TE grade significantly increased the rates of clinical pregnancy (OR = 0.59, 95 % CI, 0.35-0.99, P = 0.045, grade (A + B) vs grade C) and live birth (OR = 0.55, 95 % CI, 0.32-0.94, P = 0.029, grade (A + B) vs grade C). And the association between TE grade and the rate of live birth didn't change after the number of repeated cycles was adjusted (OR = 0.55, 95 % CI, 0.32-0.95, P = 0.033, grade (A + B) vs grade C). The number of repeated cycles was a confounding factor significantly different between the live birth and no live birth groups. By contrast, neither blastocoele expansion nor inner cell mass was statistically related to the rates of clinical pregnancy, live birth and miscarriage. CONCLUSIONS: Our data firstly provided the evidence that TE grading, but not ICM grading, was significantly associated with the clinical pregnancy rate and live birth rate in vitrified-warmed blastocyst transfer cycles in a Chinese population. TE morphology may help predict outcomes of pregnancy in single blastocyst transfer. PMID- 25123129 TI - The biomechanics of biodegradable versus titanium interference screw fixation for anterior cruciate ligament augmentation and reconstruction. AB - PURPOSE: The ligament augmentation and reconstruction system (LARS) is one of the options available for anterior cruciate ligament (ACL) reconstruction. To date, however, there are no published data regarding the biomechanical properties of LARS fixation for ACL reconstruction. The aim of this study was to investigate the biomechanical properties of various LARS interference-screw fixations. METHODS: A total of 100 LARS ligaments were fixed in porcine femurs with five different interference screws (four biodegradable screws and one titanium interference screw) introduced from inside-out or extra-articularly outside-in. Each group consisted of ten specimens. The constructs were cyclically stretched and subsequently loaded until failure. We evaluated the maximum load before failure, elongation during cyclic loading, stiffness, and failure mode. RESULTS: Elongation during cyclical loading for all devices tested was significantly larger between the first and 20th cycles than between the 20th and 500th cycles (p < 0.05). Maximum failure load was not significantly lower for the biodegradable screws than for the titanium screws (p > 0.05). All specimens failed because of ligament pull-out from the bony tunnel. CONCLUSIONS: Our findings suggest that biomechanical secure fixation of the LARS for ACL reconstruction can be achieved using either biodegradable or titanium interference screws. The stability of fixation is independent of the approach, type of investigation, and type of fixation (extra-articular outside-in or intra articular inside-out). PMID- 25123130 TI - Self-management and bipolar disorder--a clinician's guide to the literature 2011 2014. AB - This review provides clinicians and individuals with bipolar disorder (BD) with an overview of evidence-based skills shown to be effective in BD and amenable to self-management including psychoeducation; monitoring moods, medications, and social function; sleep hygiene; setting goals and relapse plans; and healthy lifestyles (physical activity, healthy eating, weight loss and management, medical comorbidities). Currently available self-management resources for BD are summarized by mode of delivery (workbooks, mobile technologies, internet, and peer-led interventions). Regardless of the self-management intervention/topic, the research suggests that personally tailored interventions of longer duration and greater frequency may be necessary to achieve the maximal benefit among individuals with BD. Means to support these self-management interventions as self sustaining identities are critically needed. Hopefully, the recent investment in patient-centered research and care will result in best practices for the self management of BD by mode of delivery. Since self-management of BD should complement rather than replace medical care, clinicians need to partner with their patients to incorporate and support advances in self-management for individuals with BD. PMID- 25123131 TI - A combination of eicosapentaenoic acid-free fatty acid, epigallocatechin-3 gallate and proanthocyanidins has a strong effect on mTOR signaling in colorectal cancer cells. AB - Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. The development of novel anti-CRC agents able to overcome drug resistance and/or off target toxicity is of pivotal importance. The mammalian target of rapamycin (mTOR) plays a critical role in CRC, regulating protein translation and controlling cell growth, proliferation, metabolism and survival. The aim of this study was to explore the effect of a combination of three natural compounds, eicosapentaenoic acid-free fatty acid (EPA-FFA), epigallocatechin-3-gallate (EGCG) and proanthocyanidins (grape seed [GS] extract) at low cytotoxic concentrations on CRC cells and test their activity on mTOR and translational regulation. The CRC cell lines HCT116 and SW480 were treated for 24h with combinations of EPA-FFA (0-150 uM), EGCG (0-175 uM) and GS extract (0-15 uM) to evaluate the effect on cell viability. The low cytotoxic combination of EPA-FFA 150 uM, EGCG 175 uM and GS extract 15 uM completely inhibited the mTOR signaling in HCT116 and SW480 cells, reaching an effect stronger than or comparable to that of the mTOR inhibitor Rapamycin in HCT116 or SW480 cells, respectively. Moreover, the treatment led to changes of protein translation of ribosomal proteins, c-Myc and cyclin D1. In addition, we found a reduction of clonal capability in both cell lines, with block of cell cycle in G0G1 and induction of apoptosis. Our data suggest that the low cytotoxic combination of EPA-FFA, EGCG and GS extract, tested for the first time here, inhibits mTOR signaling and thus could be considered for CRC treatment. PMID- 25123133 TI - Defective RAGE activity in embryonal rhabdomyosarcoma cells results in high PAX7 levels that sustain migration and invasiveness. AB - Rhabdomyosarcoma is a muscle-derived malignant tumor mainly affecting children. The most frequent variant, embryonal rhabdomyosarcoma (ERMS) is characterized by overexpression of the transcription factor, PAX7 which prevents ERMS cells from exiting the cell cycle and terminally differentiating. However, a role for PAX7 in the invasive properties of ERMS cells has not been investigated in detail thus far. Here we show that ectopic expression of receptor for advanced glycation end products (RAGE) in human ERMS cells results in the activation of a RAGE/myogenin axis which downregulates PAX7 by transcriptional and post-translational mechanisms, as in normal myoblasts, and reduces metastasis formation. High PAX7 sustains migration and invasiveness in ERMS cells by upregulating EPHA3 and EFNA1 and downregulating NCAM1 thus decreasing the neural cell adhesion molecule (NCAM)/polysialylated-NCAM ratio. Microarray gene expression analysis shows that compared with the RAGE(-ve) TE671/WT cells and similarly to primary human myoblasts, TE671/RAGE cells show upregulation of genes involved in muscle differentiation and cell adhesion, and downregulation of cell migration related and major histocompatibility complex class I genes. Our data reveal a link between PAX7 and metastasis occurrence in ERMSs, and support a role for the RAGE/myogenin axis in metastasis suppression. Thus, low RAGE expression in ERMS primary tumors may be predictive of metastatic behavior. PMID- 25123132 TI - Overexpression of miR-146a in basal-like breast cancer cells confers enhanced tumorigenic potential in association with altered p53 status. AB - The tumor suppressor p53 is the most frequently mutated gene in human cancers, mutated in 25-30% of breast cancers. However, mutation rates differ according to breast cancer subtype, being more prevalent in aggressive estrogen receptor negative tumors and basal-like and HER2-amplified subtypes. This heterogeneity suggests that p53 may function differently across breast cancer subtypes. We used RNAi-mediated p53 knockdown (KD) and antagomir-mediated KD of microRNAs to study how gene expression and cellular response to p53 loss differ in luminal versus basal-like breast cancer. As expected, p53 loss caused downregulation of established p53 targets (e.g. p21 and miR-34 family) and increased proliferation in both luminal and basal-like cell lines. However, some p53-dependent changes were subtype specific, including expression of miR-134, miR-146a and miR-181b. To study the cellular response to miR-146a upregulation in p53-impaired basal-like lines, antagomir KD of miR-146a was performed. KD of miR-146a caused decreased proliferation and increased apoptosis, effectively ablating the effects of p53 loss. Furthermore, we found that miR-146a upregulation decreased NF-kappaB expression and downregulated the NF-kappaB-dependent extrinsic apoptotic pathway (including tumor necrosis factor, FADD and TRADD) and antagomir-mediated miR-146a KD restored expression of these components, suggesting a plausible mechanism for miR-146a-dependent cellular responses. These findings are relevant to human basal like tumor progression in vivo, since miR-146a is highly expressed in p53 mutant basal-like breast cancers. These findings suggest that targeting miR-146a expression may have value for altering the aggressiveness of p53 mutant basal like tumors. PMID- 25123134 TI - The effects of synthetic oligopeptide derived from enamel matrix derivative on cell proliferation and osteoblastic differentiation of human mesenchymal stem cells. AB - Enamel matrix derivative (EMD) is widely used in periodontal tissue regeneration therapy. However, because the bioactivity of EMD varies from batch to batch, and the use of a synthetic peptide could avoid use from an animal source, a completely synthetic peptide (SP) containing the active component of EMD would be useful. In this study an oligopeptide synthesized derived from EMD was evaluated for whether it contributes to periodontal tissue regeneration. We investigated the effects of the SP on cell proliferation and osteoblast differentiation of human mesenchymal stem cells (MSCs), which are involved in tissue regeneration. MSCs were treated with SP (0 to 1000 ng/mL), to determine the optimal concentration. We examined the effects of SP on cell proliferation and osteoblastic differentiation indicators such as alkaline phosphatase activity, the production of procollagen type 1 C-peptide and osteocalcin, and on mineralization. Additionally, we investigated the role of extracellular signal related kinases (ERK) in cell proliferation and osteoblastic differentiation induced by SP. Our results suggest that SP promotes these processes in human MSCs, and that ERK inhibitors suppress these effects. In conclusion, SP promotes cell proliferation and osteoblastic differentiation of human MSCs, probably through the ERK pathway. PMID- 25123135 TI - Mammalian cytochrome P450-dependent metabolism of polychlorinated dibenzo-p dioxins and coplanar polychlorinated biphenyls. AB - Polychlorinated dibenzo-p-dioxins (PCDDs) and coplanar polychlorinated biphenyls (PCBs) contribute to dioxin toxicity in humans and wildlife after bioaccumulation through the food chain from the environment. The authors examined human and rat cytochrome P450 (CYP)-dependent metabolism of PCDDs and PCBs. A number of human CYP isoforms belonging to the CYP1 and CYP2 families showed remarkable activities toward low-chlorinated PCDDs. In particular, human CYP1A1, CYP1A2, and CYP1B1 showed high activities toward monoCDDs, diCDDs, and triCDDs but no detectable activity toward 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD). Large amino acids located at putative substrate-recognition sites and the F-G loop in rat CYP1A1 contributed to the successful metabolism of 2,3,7,8-tetraCDD. Rat, but not human, CYP1A1 metabolized 3,3',4,4',5-pentachlorobiphenyl (CB126) to two hydroxylated metabolites. These metabolites are probably less toxic than is CB126, due to their higher solubility. Homology models of human and rat CYP1A1s and CB126 docking studies indicated that two amino acid differences in the CB126 binding cavity were important for CB126 metabolism. In this review, the importance of CYPs in the metabolism of dioxins and PCBs in mammals and the species-based differences between humans and rats are described. In addition, the authors reveal the molecular mechanism behind the binding modes of dioxins and PCBs in the heme pocket of CYPs. PMID- 25123136 TI - Association between phosphatase related gene variants and coronary artery disease: case-control study and meta-analysis. AB - Recent studies showed that the serum alkaline phosphatase is an independent predictor of the coronary artery disease (CAD). In this work, we aimed to summarize the association between three phosphatase related single nucleotide polymorphisms (rs12526453, rs11066301 and rs3828329) and the risk of CAD in Han Chinese. Our results showed that the rs3828329 of the ACP1 gene was closely related to the risk of CAD in Han Chinese (OR = 1.45, p = 0.0006). This significant association of rs3828329 with CAD was only found in the females (Additive model: OR = 1.80, p = 0.001; dominant model: OR = 1.69, p = 0.03; recessive model: OR = 1.96, p = 0.0008). Moreover, rs3828329 was likely to exert its effect in females aged 65 years and older (OR = 2.27, p = 0.001). Further meta-analyses showed that the rs12526453 of PHACTR11 gene (OR = 1.14, p < 0.0001, random-effect method) and the rs11066301 of PTPN11 gene (OR = 1.15, p < 0.0001, fixed-effects method) were associated with CAD risk in multiple populations. Our results showed that the polymorphisms rs12526453 and rs11066301 are significantly associated with the CAD risk in multiple populations. The rs3828329 of ACP1 gene is also a risk factor of CAD in Han Chinese females aged 65 years and older. PMID- 25123137 TI - Angiotensin I-converting enzyme (ACE) inhibitory activity and ACE inhibitory peptides of salmon (Salmo salar) protein hydrolysates obtained by human and porcine gastrointestinal enzymes. AB - The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE) inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes) and ex vivo digestion (with human gastrointestinal enzymes). Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50%) of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes. PMID- 25123139 TI - [Official experimental testing of biomedical products. Regulatory frame and importance of for quality, safety and efficacy]. AB - The official experimental testing of biomedicinal products provides a very significant contribution to ensuring quality, safety and efficacy of these indispensable medicines. Already in the prelicensing phase or to elucidate clusters of increased adverse effects, official medicinal control laboratories are committed to perform experimental testing. The official batch release can be seen as external quality control of the manufacturer's release testing. For proficient performance in these tasks, scientific research is required, in particular on the development and refinement of test methods, and considering the continuous development of innovative biomedicinal products. This article is aimed at introducing the present thematic issue and in particular the regulatory basis of experimental product testing, and illustrates by means of several examples its great importance for the sake of the patients. PMID- 25123138 TI - Melatonin suppresses hypoxia-induced migration of HUVECs via inhibition of ERK/Rac1 activation. AB - Melatonin, a naturally-occurring hormone, possesses antioxidant properties and ameliorates vascular endothelial dysfunction. In this study, we evaluate the impact of melatonin on the migratory capability of human umbilical vein endothelial cells (HUVECs) to hypoxia and further investigate whether ERK/Rac1 signaling is involved in this process. Here, we found that melatonin inhibited hypoxia-stimulated hypoxia-inducible factor-1alpha (HIF-1alpha) expression and cell migration in a dose-dependent manner. Mechanistically, melatonin inhibited Rac1 activation and suppressed the co-localized Rac1 and F-actin on the membrane of HUVECs under hypoxic condition. In addition, the blockade of Rac1 activation with ectopic expression of an inactive mutant form of Rac1-T17N suppressed HIF 1alpha expression and cell migration in response to hypoxia, as well, but constitutive activation of Rac1 mutant Rac1-V12 restored HIF-1alpha expression, preventing the inhibition of melatonin on cell migration. Furthermore, the anti Rac1 effect of melatonin in HUVECs appeared to be associated with its inhibition of ERK phosphorylation, but not that of the PI3k/Akt signaling pathway. Taken together, our work indicates that melatonin exerts an anti-migratory effect on hypoxic HUVECs by blocking ERK/Rac1 activation and subsequent HIF-1alpha upregulation. PMID- 25123140 TI - [Viral safety of biological medicinal products]. AB - Viral safety of blood donations, plasma products, viral vaccines and gene therapy medicinal products, biotechnical-derived products and tissue and cell therapy products is a particular challenge. These products are manufactured using a variety of human or animal-derived starting materials and reagents; therefore, extensive testing of donors and of cell banks established for production is required. Furthermore, the viral safety of reagents, such as bovine sera, porcine trypsin and human transferrin or albumin needs to be considered. Whenever possible, manufacturing steps for inactivation or removal of viruses should be introduced; however, sometimes it is not possible to introduce such steps for tissues or cell-based medicinal products as the activity and viability of cells will be compromised. It might be possible to implement steps for inactivation or removal of potential contaminating enveloped viruses only for production of small and stable non-enveloped viral gene vectors. PMID- 25123141 TI - Comparing mortality among adult, general intensive care units in England with varying intensivist cover patterns: a retrospective cohort study. AB - INTRODUCTION: Research has demonstrated that intensivist-led care of the critically ill is associated with reduced intensive care unit (ICU) and hospital mortality. The objective of this study was to evaluate whether a relation exists between intensivist cover pattern (for example, number of days of continuous cover) and patient outcomes among adult general ICUs in England. METHODS: We conducted a retrospective cohort study by using data from a pooled case mix and outcome database of adult general critical care units participating in the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme. Consecutive admissions to participating units for the years 2010 to 2011 were linked to a survey of intensivist cover practices. Our primary outcome of interest was mortality at ultimate discharge from acute-care hospital. RESULTS: The analysis included 80,122 patients admitted to 130 ICUs in 128 hospitals. Multivariable logistic regression analysis was used to assess the relation between intensivist cover patterns (days of continuous cover, grade of physician staffing at nighttime, and frequency of daily handovers) and acute hospital mortality, adjusting for patient case mix. No relation was seen between days of continuous cover by a single intensivist or grade of physician staffing at nighttime and acute hospital mortality. Acute hospital mortality and ICU length of stay were not associated with intensivist characteristics, intensivist full time equivalents per bed, or years of clinical experience. Intensivist participation in handover was associated with increased mortality (odds ratio, 1.27; 95% confidence interval, 1.04 to 1.55); however, only nine units reported no intensivist participation. CONCLUSIONS: We found no relation between days of continuous cover by a single intensivist or grade of physician staffing at nighttime and patient outcomes in adult, general ICUs in England. Intensivist participation in handover was associated with increased mortality; further research to confirm or refute this finding is required. PMID- 25123144 TI - The 2014 AHA/ACC valve disease guideline: new stages of disease, new treatment options, and a call for earlier intervention. PMID- 25123142 TI - Effectiveness and safety of ciclesonide in the treatment of patients with persistent allergic or non-allergic asthma in medical practice (Data from a non interventional study conducted in Austria). AB - BACKGROUND: Effectiveness and safety profile of ciclesonide in the treatment of persistent allergic or non-allergic asthma was evaluated in real-life setting in Austria. METHODS: Prospective, single-arm, 3-month observational, non interventional, open-label cohort study in patients with persistent asthma (with or without allergic component) of any severity grade was conducted. Patients were either treatment naive or switched to treatment with ciclesonide and had an indication for treatment with inhaled corticosteroids. RESULTS: In all, 307 patients (50.8% female; mean age, 45.7 years) were prescribed ciclesonide. After 3 months of observation, the percentage of patients with daily symptoms had declined from 33.2 to 3.9%, night-time symptoms from 21.8 to 5.2%, physical activity limitations from 73.9 to 24.4%, and rescue medication usage from 70.0 to 45.9%. The mean total Asthma Control Questionnaire (ACQ) score was 2.32 +/- 1.14 at the first and 1.08 +/- 0.88 at the final visit. The number of patients with well-controlled asthma (ACQ score < 1) increased considerably from 11.0% at baseline to 52.2% at study end. Clinically important mean improvements were observed in the total self-assessed Asthma Quality of Life score and all four domain scores. The mean forced expiratory volume in 1 s (FEV1) increased by 0.3 L from 2.60 +/- 0.87 L to 2.89 +/- 0.86 L, and the mean FEV1% predicted increased from 75.1 +/- 15.4% to 83.7 +/- 14.9%. Incidence of adverse drug reactions (ADRs) was low (4 ADRs in 3 of 307 patients, or 1.0%). CONCLUSION: This study confirmed the effectiveness and safety of ciclesonide under routine conditions in Austria. Improvements in symptom control, lung function, and quality of life were observed. Ciclesonide was well tolerated. PMID- 25123143 TI - Auditory hallucinations associated with nitrofurantoin use: case report and review of the literature. AB - OBJECTIVE: In this case report, we present an 83-year-old Caucasian immune competent woman with Alzheimer's disease and organic personality disorder who developed auditory hallucinations when treated with two nitrofurantoin (NF) tablets (100 mg) every 12 h because of acute cystitis due to extended-spectrum beta-lactamase-positive Escherichia coli. An 83-year-old Caucasian woman with Alzheimer's disease developed auditory hallucinations 2 days after intake of two NF tablets (100 mg) daily. After thorough discussion, it was decided not to rechallenge with NF because of the serious adverse effect. After NF discontinuation suggested by clinical pharmacist and switching to imipenem 500 mg and cilastatin 500 mg three times daily for 7 days, symptoms significantly improved the next day. No other drugs known to interact with NF were administered. DISCUSSION: NF-induced adverse effects have been reported frequently, but NF-induced auditory hallucinations with early onset in an immune competent geriatric patient, without previous reported hallucinations or seizures, have not been reported in the literature. Scoring according to the Naranjo adverse drug reaction scale revealed a probable relationship between auditory hallucinations and NF use in our patient (6 points). The exact mechanism for the central nervous system (CNS) toxicity of NF in this patient is not known, but we believe that the CNS penetration of NF may result in the accumulation of toxic drug levels in CNS. CONCLUSION: This case report can be used to remind clinicians and clinical pharmacists of keeping in mind the potential of NF associated with auditory hallucinations, which can be easily confused with more serious conditions. PMID- 25123147 TI - Bronze, silver and gold: functionalized group 11 organotin sulfide clusters. AB - The synthesis, properties and reactivity of group 11 organotin sulfide clusters [(R(1)Sn)4(SnCl)2(MPPh3)2S8] (M = Cu, Ag), [(R(3)Sn)10Ag10S20], and [(R(1,3)Sn)2(AuPPh3)2S4] with covalently bound, carbonyl or hydrazine-terminated ligands R(1) = CMe2CH2C(Me)O or R(3) = CMe2CH2C(Me)NNH2 are reported. PMID- 25123148 TI - Ultrasensitive detection of cancer cells and glycan expression profiling based on a multivalent recognition and alkaline phosphatase-responsive electrogenerated chemiluminescence biosensor. AB - A multivalent recognition and alkaline phosphatase (ALP)-responsive electrogenerated chemiluminescence (ECL) biosensor for cancer cell detection and in situ evaluation of cell surface glycan expression was developed on a poly(amidoamine) (PAMAM) dendrimer-conjugated, chemically reduced graphene oxide (rGO) electrode interface. In this strategy, the multivalency and high affinity of the cell-targeted aptamers on rGO provided a highly efficient cell recognition platform on the electrode. The ALP and concanavalin A (Con A) coated gold nanoparticles (Au NPs) nanoprobes allowed the ALP enzyme-catalyzed production of phenols that inhibited the ECL reaction of Ru(bpy)3(2+) on the rGO electrode interface, affording fast and highly sensitive ECL cytosensing and cell surface glycan evaluation. Combining the multivalent aptamer interface and ALP nanoprobes, the ECL cytosensor showed a detection limit of 38 CCRF-CEM cells per mL in human serum samples, broad dynamic range and excellent selectivity. In addition, the proposed biosensor provided a valuable insight into dynamic profiling of the expression of different glycans on cell surfaces, based on the carbohydrates recognized by lectins applied to the nanoprobes. This biosensor exhibits great promise in clinical diagnosis and drug screening. PMID- 25123149 TI - Novel tunneling system for implantation of percutaneous nerve field stimulator electrodes: a technical note. AB - INTRODUCTION: The field of neuromodulation continues to grow, especially in the area of pain management. Percutaneous nerve field stimulation continues to gain significant popularity for chronic, focal, and intractable neuropathic pain. MATERIALS AND METHODS: Tuohy needles have been traditionally used as the instrument of choice for subcutaneous implantation of peripheral field stimulators. The ON-Q(r) Tunneling System (Braun Melsungen AG, Melsungen, Germany) provides an adaptable option for subcutaneous implantation of electrodes, with a variety of lengths and gauges available. This system uses a disposable blunt needle and a peel-away sheath and is firm but malleable. Gentle curves can be applied to the stylet prior to implantation. The blunt, malleable nature of the needle and the soft Silastic sheath allow for applications in areas with greater curvature, such as the face, and ensure a subcutaneous placement. CONCLUSIONS: The great adaptability of this system allows for implantation of electrodes subcutaneously with efficacy and ease. Here we present a technical note on the use of this system for subcutaneous implantation of peripheral nerve field stimulators. PMID- 25123150 TI - Elevated APOBEC3B correlates with poor outcomes for estrogen-receptor-positive breast cancers. AB - Recent observations connected DNA cytosine deaminase APOBEC3B to the genetic evolution of breast cancer. We addressed whether APOBEC3B is associated with breast cancer clinical outcomes. APOBEC3B messenger RNA (mRNA) levels were related in 1,491 primary breast cancers to disease-free (DFS), metastasis-free (MFS), and overall survival (OS). For independent validation, APOBEC3B mRNA expression was associated with patient outcome data in five additional cohorts (over 3,500 breast cancer cases). In univariate Cox regression analysis, increasing APOBEC3B expression as a continuous variable was associated with worse DFS, MFS, and OS (hazard ratio [HR] = 1.20, 1.21, and 1.24, respectively; all P < .001). Also, in untreated ER-positive (ER+), but not in ER-, lymph-node-negative patients, high APOBEC3B levels were associated with a poor DFS (continuous variable: HR = 1.29, P = .001; dichotomized at the median level, HR = 1.66, P = .0002). This implies that APOBEC3B is a marker of pure prognosis in ER + disease. These findings were confirmed in the analyses of five independent patient sets. In these analyses, APOBEC3B expression dichotomized at the median level was associated with adverse outcomes (METABRIC discovery and validation, 788 and 706 ER + cases, disease-specific survival (DSS), HR = 1.77 and HR = 1.77, respectively, both P < .001; Affymetrix dataset, 754 ER + cases, DFS, HR = 1.57, P = 2.46E-04; NKI295, 181 ER + cases, DFS, HR = 1.72, P = .054; and BIG 1-98, 1,219 ER + cases, breast-cancer-free interval (BCFI), HR = 1.42, P = 0.0079). APOBEC3B is a marker of pure prognosis and poor outcomes for ER + breast cancer, which strongly suggests that genetic aberrations induced by APOBEC3B contribute to breast cancer progression. PMID- 25123152 TI - Association between dental caries activity, quality of life and obesity in Brazilian adolescents. AB - OBJECTIVES: The impact of oral conditions on quality of life in overweight/obesity needs to be elucidated. The aim of this study was to evaluate the association between dental caries activity, quality of life and obesity in Brazilian adolescents. MATERIALS AND METHODS: This study was conducted at public schools in Brazil, on a sample of 202 adolescents, 12 years of age. For anthropometric evaluation, the body mass index (BMI)-for-age was used. In oral examinations, the Decayed, Missing, Filled teeth (DMFT), significant caries (SiC) and dental caries activity (DCA) indices were used (kappa > 0.94). The Child-Oral Impacts on Daily Performance (Child-OIDP) index was applied. The sample was divided into two groups: O (overweight/obese; n = 101) and N (normal weight; n = 101). For data analysis, chi-square, odds ratio (OR), Wilcoxon and Pearson correlation tests were used (P < 0.05). RESULTS: The DMFT scores were 1.67 and 2.12 and the SiC scores were 3.85 and 4.26 for groups O and N, respectively. BMI for-age was significantly related to DCA (OR = 0.579; P < 0.000) and to SiC (OR = 0.649; P = 0.024). There were differences between the groups in eating, cleaning mouth, emotional status, smiling, studying and the overall Child-OIDP (P < 0.05). Positive associations between the impacts on eating, cleaning mouth and smiling were found (P < 0.05). DMFT values showed significant correlation with the emotional status performance in group O and the DCA was positively correlated with performance at school in group O (P < 0.05). CONCLUSION: Obesity, dental caries and quality of life were not correlated. Adolescents with normal weight presented a low perception of the impact of oral conditions on quality of life; however, it seemed to affect psychological aspects in their daily performances. Providing adolescents with nutritional assistance may prevent obesity and dental caries, and improve their quality of life. PMID- 25123153 TI - The compassion deficit and what to do about it: a response to Paley. PMID- 25123151 TI - RhoC upregulation is correlated with reduced E-cadherin in human breast cancer specimens after chemotherapy and in human breast cancer MCF-7 cells. AB - Therapy-resistant cancer cells are a major problem in cancer research. Recent studies suggest that the epithelial-mesenchymal transition (EMT) is a key mechanism in therapy resistance. Yet, the expressions of EMT markers, EMT core regulators, and a stem cell marker of BMI1 during chemotherapy have been poorly analyzed in clinical breast cancer specimens. In the present study, we investigated the roles of RhoC under chemotherapy to follow up on earlier findings demonstrating the involvement of RhoC in prostate cancer resistance to endocrine therapy. Immunohistochemically, E-cadherin expression was significantly lower in human breast cancer specimens analyzed after chemotherapy than specimens biopsied before chemotherapy. Significant upregulation of fibronectin, a mesenchymal EMT marker, was found in post-chemotherapy analysis. A study of the EMT core regulators of SNAIL1, SNAIL2, TWIST1, and a well-known stem cell marker of BMI1 revealed no post-chemotherapy upregulation of these molecules. In contrast, RhoC expression was significantly upregulated in post-chemotherapy breast cancer specimens. MCF-7 cells stably transfected with the constitutive active (CA) RhoC plasmid manifested a reduced level of E-cadherin at the peripheries and disorganization of actin fibers, with no accompanying upregulation of SNAIL1, SNAIL2, TWIST1, or BMI1 in Western blots. Exposure of etoposide on MCF-7 cells showed RhoC upregulation together with reduced membranous expression of E-cadherin and disorganization of actin fibers. In MTT assay, however, the CA-RhoC-expressing MCF-7 cells failed to show chemotherapy resistance under etoposide treatment. Taken in sum, RhoC may contribute to an EMT like process in human breast cancer during chemotherapy. PMID- 25123155 TI - Ambulatory measurement of the ECG T-wave amplitude. AB - Ambulatory recording of the preejection period (PEP) can be used to measure changes in cardiac sympathetic nervous system (SNS) activity under naturalistic conditions. Here, we test the ECG T-wave amplitude (TWA) as an alternative measure, using 24-h ambulatory monitoring of PEP and TWA in a sample of 564 healthy adults. The TWA showed a decrease in response to mental stress and a monotonic decrease from nighttime sleep to daytime sitting and more physically active behaviors. Within-participant changes in TWA were correlated with changes in the PEP across the standardized stressors (r = .42) and the unstandardized naturalistic conditions (mean r = .35). Partialling out changes in heart rate and vagal effects attenuated these correlations, but they remained significant. Ambulatory TWA cannot replace PEP, but simultaneous recording of TWA and PEP provides a more comprehensive picture of changes in cardiac SNS activity in real life settings. PMID- 25123154 TI - Contrasting effects of geriatric versus general medical multimorbidity on quality of ambulatory care. AB - OBJECTIVES: To determine whether greater burden of geriatric conditions would have contrasting effects on quality of care (QOC) than nongeriatric, general medical conditions. DESIGN: Cross-sectional observation over 1 year of ambulatory care. SETTING: The Assessing Care of Vulnerable Elders-2 study. PARTICIPANTS: Older adults prospectively screened for falls, incontinence, and dementia (N = 644). MEASUREMENTS: Participant-level QOC in absolute percentage points calculated using 65 ambulatory care care-process quality indicators (QIs) for 13 general medical and geriatric conditions (#QIs provided/#QIs eligible). Secondary outcomes were geriatric QOC (a subset of 38 geriatric care QIs) and medical QOC (the 27 remaining nongeriatric QIs). Exposure variables were number of six medical conditions (medical comorbidity) and six geriatric conditions (geriatric comorbidity), controlling for age, sex, number of primary care visits, and site. RESULTS: Medical and geriatric comorbidity were unrelated to each other (correlation coefficient = 0.04, P = .27) yet had opposite effects on QOC. Each additional medical condition was associated with a 3.2-percentage point (95% confidence interval (CI) = 2.3-4.2 percentage point) increment in QOC, and each additional geriatric condition was associated with 4.9-percentage point (95% CI = 3.5-6.5 percentage point) decrement in QOC. Participants with greater geriatric comorbidity received poorer medical and geriatric QOC. CONCLUSION: Greater burden of geriatric conditions, or geriatric multimorbidity, is associated with poorer QOC. Geriatric multimorbidity should be targeted for better care using a comprehensive approach. PMID- 25123157 TI - Early angiography and clot retrieval in treatment of acute superior mesenteric artery embolus. PMID- 25123156 TI - Impaired fear recognition and attentional set-shifting is associated with brain structural changes in alcoholic patients. AB - Alcoholic patients with multiple detoxifications/relapses show cognitive and emotional deficits. We performed structural magnetic resonance imaging and examined performance on a cognitive flexibility task (intra-extradimensional set shift and reversal; IED). We also presented subjects with fearful, disgust and anger facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n = 12) or singly detoxified patients (SDTx; n = 17) and social drinker controls (n = 31). Alcoholic patients were less able than controls to change their behavior in accordance with the changing of the rules in the IED and they were less accurate in recognizing fearful expressions in particular. They also showed lower gray matter volume compared with controls in frontal brain areas, including inferior frontal cortex (IFC) and insula that mediate emotional processing, inferior parietal lobule and medial frontal cortex that mediate attentional and motor planning processes, respectively. Impairments in performance and some of the regional decreases in gray matter were greater in MDTx. Gray matter volume in IFC in patients was negatively correlated with the number of detoxifications, whereas inferior parietal lobule was negatively correlated with the control over drinking score (impaired control over drinking questionnaire). Performance in IED was also negatively correlated with gray matter volume in IFC/BA47, whereas recognition of fearful faces was positively correlated with the IFC gray matter. Repeated episodes of detoxification from alcohol, related to severity of dependency, are coupled with altered brain structure in areas of emotional regulation, attention and motor planning. Such changes may confer increased inability to switch behavior according to environmental demands and social incompetence, contributing to relapse. PMID- 25123158 TI - Does amplitude-integrated electroencephalogram background pattern correlate with cerebral injury in neonates with hypoxic-ischaemic encephalopathy? AB - AIMS: To determine the correlation between amplitude-integrated electroencephalogram (aEEG) background pattern and cerebral magnetic resonance imaging (MRI) in infants with hypoxic-ischaemic encephalopathy (HIE) and to examine whether the correlation changes with therapeutic hypothermia. METHODS: We included 38 term-born infants with HIE of whom 17 were cooled. All were continuously monitored with aEEG. Background pattern was scored at the beginning and the end of the recording. Cerebral MRI was obtained on median day 5 (2-11 days). Abnormalities were classified using a predefined scoring system for basal ganglia, watershed and overall injury, and then grouped into mild-moderate and severe. RESULTS: Abnormal aEEG background pattern correlated with more severe cerebral injury on MRI in the non-cooled infants (P < 0.01). In addition, cooled infants had less severe cerebral injury than non-cooled infants, in particular on T2-weighted images (watershed P = 0.04 and total injury score = 0.07). CONCLUSIONS: Abnormal aEEG background pattern is predictive of abnormal MRI, but therapeutic hypothermia seems to reduce this association. Thus, when cooling is applied in a clinical setting, the predictive value of aEEG may be limited. PMID- 25123159 TI - Immunohistochemical panel for the diagnosis of Hirschsprung's disease using antibodies to MAP2, calretinin, GLUT1 and S100. AB - AIMS: The diagnosis of Hirschsprung's disease is currently based on the identification of aganglionosis and the presence of an increase in acetylcholinesterase-positive hypertrophic nerve fibres in the large bowel submucosa. However, acetylcholinesterase staining is laborious and requires a skilled technician. The aim of this study was to identify a method for diagnosing Hirschsprung's disease reliably using an immunohistochemical panel of recently proposed markers. METHODS AND RESULTS: Sixty-nine specimens from 37 patients were evaluated. MAP2 and calretinin antibodies were shown to stain ganglia reliably in the submucosal and myenteric plexuses of normal tissue. By contrast, reduced staining of ganglia was observed in patients with Hirschsprung's disease. Staining for GLUT1 and S100 was used to evaluate the number and thickness of nerve fibres. Gain of GLUT1 and S100 expression was in contrast to the loss of calretinin and MAP2. Hypertrophic submucosal nerve fibres in Hirschsprung's disease develop a perineurium with a ring-like GLUT1 staining pattern similar in size and intensity to that observed in deeper subserosal tissue. CONCLUSIONS: The diagnosis of Hirschsprung's disease using immunohistochemical panels could be as accurate as with conventional frozen section techniques. In particular, the use of a combination of markers for ganglia and hypertrophic nerve fibres highlighting a prominent perineurium in Hirschsprung's disease could be an alternative method. PMID- 25123160 TI - The use of endoscopic cyclophotocoagulation for moderate to advanced glaucoma. AB - Endoscopic Cyclophotocoagulation (ECP) is a glaucoma surgery designed to reduce the intraocular pressure (IOP) by partially ablating the ciliary processes to decrease aqueous humour production and secretion. The aim of this paper is to review the literature regarding the background, indications and results of the surgery. Although there are case reports of visually devastating complications, including persistent hypotony and phthisis, the use of ECP is often reported in eyes with advanced diseases. When compared with both trabeculectomy and aqueous shunt implantation, the visual outcomes were better with ECP while the IOP outcomes were very similar. The evidence supports ECP as a very effective surgical option in recalcitrant glaucoma while some evidence supports its safety for use as a primary procedure. PMID- 25123161 TI - The stars within the melanocytic garden: unusual variants of Spitz naevi. AB - BACKGROUND: Spitz naevi may present a wide spectrum of morphologies. Histopathologically, many variants, including desmoplastic, angiomatoid, verrucous/polypoid, plexiform, pagetoid, halo, myxoid, granulomatous and tubular Spitz naevi have been described. Clinical and dermoscopic features of these unusual variants of Spitz naevi have been reported only rarely. OBJECTIVES: The aim of this study is to describe clinical, dermoscopic and histopathological features of uncommon morphological variants of Spitz naevi in order to raise awareness among clinicians about their peculiar patterns of presentation. METHODS: We searched our image database retrospectively from 2004 to 2014 for images of excised tumours using Spitz/Reed naevus as a keyword. RESULTS: A total of 307 excised skin lesions with a histopathological diagnosis of Spitz/Reed naevus were found. Among those we identified 13 uncommon variants of Spitz naevi including six cases of desmoplastic Spitz naevus, five cases of angiomatoid Spitz naevus and two cases of verrucous Spitz naevus. These lesions did not fulfil the already described dermoscopic criteria of Spitz naevi, with the exception of angiomatoid Spitz naevi, exhibiting a pinkish background and dotted vessels in dermoscopy. Desmoplastic Spitz naevi may be difficult to differentiate from dermatofibroma clinically, and from melanoma under dermoscopic examination. Verrucous Spitz naevi, despite their relatively unusual clinical features, show reassuring morphological clues histologically, which allows the differential diagnosis from an atypical spitzoid tumour. CONCLUSIONS: In all cases an atypical melanocytic lesion could not be excluded under dermoscopy, thus warranting excision and histopathological examination. PMID- 25123162 TI - Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5). AB - BACKGROUND: The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age. METHOD: A total of 1719 children, with the breakdown into groupings of <30, 30-36, and >= 37 weeks gestation at birth, contributed to the primary outcome: death or survival with a disability in one of the following domains: neuromotor, neurosensory, and neurobehavioral/emotional disability and were included in this analysis. RESULTS: Gestational age at birth was strongly associated with the primary outcome, p < 0.001. Overall, the interaction between ACS groups and gestational age at birth was not significant, p = 0.064. Specifically, in the 2 preterm categories, there was no difference in the primary outcome between single vs. multiple ACS therapy. However, for infants born >=37 weeks gestation, there was a statistically significant increase in the risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to 38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p = 0.037. CONCLUSION: Preterm birth (<37 weeks gestation) remained the primary factor contributing to an adverse outcome regardless of the number of courses of ACS therapy. Children born >= 37 weeks and exposed to multiple ACS therapy may have an increased risk of neurodevelopmental/neurosensory impairment by 5 years of age. To optimize outcomes for infants/children, efforts in reducing the incidence of preterm birth should remain the primary focus in perinatal research. TRIAL REGISTRATION: This study has been registered at (identifier NCT00187382). PMID- 25123163 TI - Itch-associated peptides: RNA-Seq and bioinformatic analysis of natriuretic precursor peptide B and gastrin releasing peptide in dorsal root and trigeminal ganglia, and the spinal cord. AB - BACKGROUND: Three neuropeptides, gastrin releasing peptide (GRP), natriuritic precursor peptide B (NPPB), and neuromedin B (NMB) have been proposed to play roles in itch sensation. However, the tissues in which these peptides are expressed and their positions in the itch circuit has recently become the subject of debate. Here we used next-gen RNA-Seq to examine the expression of transcripts coding for GRP, NPPB, NMB, and other peptides in DRG, trigeminal ganglion, and the spinal cord as well as expression levels for their cognate receptors in these tissues. RESULTS: RNA-Seq demonstrates that GRP is not transcribed in mouse, rat, or human sensory ganglia. NPPB, which activates natriuretic peptide receptor 1 (NPR1), is well expressed in mouse DRG and less so in rat and human, whereas NPPA, which also acts on the NPR1 receptor, is expressed in all three species. Analysis of transcripts expressed in the spinal cord of mouse, rat, and human reveals no expression of Nppb, but unambiguously detects expression of Grp and the GRP-receptor (Grpr). The transcripts coding for NMB and tachykinin peptides are among the most highly expressed in DRG. Bioinformatics comparisons using the sequence of the peptides used to produce GRP-antibodies with proteome databases revealed that the C-terminal primary sequence of NMB and Substance P can potentially account for results from previous studies which showed GRP immunostaining in the DRG. CONCLUSIONS: RNA-Seq corroborates a primary itch afferent role for NPPB in mouse and potentially NPPB and NPPA in rats and humans, but does not support GRP as a primary itch neurotransmitter in mouse, rat, or humans. As such, our results are at odds with the initial proposal of Sun and Chen (2007) that GRP is expressed in DRG. By contrast, our data strongly support an itch pathway where the itch-inducing actions of GRP are exerted through its release from spinal cord neurons. PMID- 25123164 TI - Prognostic relevance of aberrant SOCS-1 gene promoter methylation in myelodysplastic syndromes patients. AB - INTRODUCTION: The inactivation of suppressor of cytokine signaling SOCS-1, a negative regulator of cytokine pathways, by hypermethylation was shown in hematological malignancies including Myelsplastic Syndromes. So far, its prognostic relevance in myelodysplastic syndromes (MDS) patients has not been understood. METHODS: Methylation status of SOCS-1 gene was analyzed in series of 100 patients using methylation-specific PCR (MS-PCR) and correlated with disease severity, progression, and survival by comparing prognostic factors such as hematological, clinical, and cytogenetics. RESULTS: Of the total of 100 MDS patients analyzed, methylation of SOCS1 gene was found in 53% patients. Also, the frequency of patients with poor and intermediate cytogenetics was observed significantly high in methylated group (P < 0.001). Moreover, the patients with methylated SOCS-1 gene had significantly more frequent disease progression as compared to the patients with unmethylated SOCS-1 gene (P < 0.006). Both progression-free survival and median overall survival were significantly shorter in patients with methylated SOCS-1 gene when compared to the patients with unmethylated SOCS-1 gene (P = 0.006 & P = 0.001, respectively). CONCLUSION: This study for the first time showed that the mathylation of SOCS-1 gene plays an important role in the disease progression and is associated with poor survival especially among the high-risk patients. This may be due to high association between SOCS1 methylation and higher risk subtypes of MDS (such as RAEB) in this study. PMID- 25123165 TI - Assessment of patients' wound-related pain experiences in University College Hospital, Ibadan, Nigeria. AB - This study was necessitated by the international recognition of wound-related pain (WRP) as a must-address issue and patient-centred concerns. The aim of this study was to assess patients' WRP experiences at rest and in relation to dressing change. This descriptive study utilised a WRP questionnaire which incorporated a visual analogue scale of 0-10 for data collection. A total of 109 patients participated in this study; 95.4% of the participants experienced wound pain at rest and during performance of activities of daily living, which were moderate (47.1%) and severe (30.8%) in intensity. Also, 91.7% of the participants experienced wound dressing change-related pain, mostly as moderate (47.0%) and severe (28.0%) pain. The major factors that worsened WRP experiences were touch/handling, change in position/movement, wound cleansing, removal of dressings and usage of honey as a dressing agent, while the use of analgesic and brief rest between dressing change were considered the major strategies that can relieve WRP. WRP experiences have been reported by patients at rest, during performance of activities of daily living and at wound dressing change. A need to incorporate WRP assessment has been observed, which is vital in improving wound care outcome. PMID- 25123167 TI - FASTQSim: platform-independent data characterization and in silico read generation for NGS datasets. AB - BACKGROUND: High-throughput next generation sequencing technologies have enabled rapid characterization of clinical and environmental samples. Consequently, the largest bottleneck to actionable data has become sample processing and bioinformatics analysis, creating a need for accurate and rapid algorithms to process genetic data. Perfectly characterized in silico datasets are a useful tool for evaluating the performance of such algorithms. Background contaminating organisms are observed in sequenced mixtures of organisms. In silico samples provide exact truth. To create the best value for evaluating algorithms, in silico data should mimic actual sequencer data as closely as possible. RESULTS: FASTQSim is a tool that provides the dual functionality of NGS dataset characterization and metagenomic data generation. FASTQSim is sequencing platform independent, and computes distributions of read length, quality scores, indel rates, single point mutation rates, indel size, and similar statistics for any sequencing platform. To create training or testing datasets, FASTQSim has the ability to convert target sequences into in silico reads with specific error profiles obtained in the characterization step. CONCLUSIONS: FASTQSim enables users to assess the quality of NGS datasets. The tool provides information about read length, read quality, repetitive and non-repetitive indel profiles, and single base pair substitutions. FASTQSim allows the user to simulate individual read datasets that can be used as standardized test scenarios for planning sequencing projects or for benchmarking metagenomic software. In this regard, in silico datasets generated with the FASTQsim tool hold several advantages over natural datasets: they are sequencing platform independent, extremely well characterized, and less expensive to generate. Such datasets are valuable in a number of applications, including the training of assemblers for multiple platforms, benchmarking bioinformatics algorithm performance, and creating challenge datasets for detecting genetic engineering toolmarks, etc. PMID- 25123166 TI - Applicable apparent diffusion coefficient of an orthotopic mouse model of gastric cancer by improved clinical MRI diffusion weighted imaging. AB - In vivo imaging studies in animal models are hindered by variables that contribute to poor image quality and measurement reliability. As such we sought to improve the diffusion coefficient (ADC) of an orthotopic mouse model of gastric cancer in diffusion-weighted images (DWI) using alginate moulding and Ultrasonic coupling medium. BGC-823 human gastric cancer cells were subcutaneously injected into the abdomen of nude mice and 1 mm(3) primary tumour was orthotopically transplanted. Alginate and coupling medium were applied to the mice and MRI (T2 and DWI) was performed for 6 weeks. Regions of interest (ROI) were drawn and liver and tumour ADC were evaluated. Using alginate moulding, the mean quality total score of DW imaging was 8.53; however, in control animals this value was 5.20 (p < 0.001). The coefficient of variation of ADC of liver in experimental and control groups were 0.071 and 0.270 (p < 0.001), respectively, suggesting this method may be helpful for DWI studies of important human diseases such as gastric cancer. PMID- 25123168 TI - Arytenoid adduction with nerve-muscle pedicle transfer vs arytenoid adduction with and without type I thyroplasty in paralytic dysphonia. AB - IMPORTANCE: Optimal glottal closure as well as symmetrical vocal fold masses and tensions are essential prerequisites for normal voice production. Successful phonosurgery depends on restoring these prerequisites to achieve long-term improvement. OBJECTIVE: To evaluate the efficacy of the laryngeal framework surgical treatments (arytenoid adduction with and without thyroplasty type I [AA +/- Th-I]) compared with arytenoid adduction combined with nerve-muscle pedicle flap transfer (AA + NMP) in unilateral vocal fold paralysis. Patterns of voice outcome were compared over a 2-year period. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of clinical records of 22 patients who presented to an institutional practice with severe paralytic dysphonia between March 1999 and December 2008, who received 2 different treatments. Postoperative follow-up was conducted over 2 years. INTERVENTIONS: Eleven patients were treated with AA +/- Th-I and 11 patients were treated with AA + NMP. MAIN OUTCOMES AND MEASURES: Vocal function was evaluated preoperatively and at 3, 12, and 24 months postoperatively. Vocal parameters evaluated were jitter, shimmer, harmonics to noise ratio (HNR), maximum phonation time (MPT), and overall grade and breathiness grade of the Grade-Roughness-Breathiness-Asthenia-Strain (GRBAS) voice scale. The outcomes of voice measurements were compared within each group across time and among the 2 groups at each time point. RESULTS: All voice parameters showed initial postoperative improvement in both groups after 3 months. Moreover, the AA + NMP group showed significant steady improvement over the 2-year follow-up, which did not occur in the AA +/- Th-I group. In the AA + NMP group, MPT increased from a mean (SD) of 5.4 (2.1) s at preoperative assessment to 21.5 (7.0) s at 24 months; jitter decreased from 8.6% (5.3%) to 1.2% (0.7%); shimmer decreased from 13.1% (6.0%) to 4.0% (1.6%); HNR increased from 3.8 (3.3) to 9.0 (0.8); overall grade of GRBAS decreased from 2.4 (0.9) to 0.2 (0.4); and breathiness grade of GRBAS decreased from 2.0 (1.0) to 0.1 (0.3). CONCLUSIONS AND RELEVANCE: Unlike the conventional laryngeal framework surgical treatments, AA + NMP provided long-term voice improvement with nearly normal voice quality. Thus, it can be considered an effective surgical treatment for paralytic dysphonia due to unilateral vocal fold paralysis associated with large glottal gap. PMID- 25123169 TI - Toward modular biological models: defining analog modules based on referent physiological mechanisms. AB - BACKGROUND: Currently, most biomedical models exist in isolation. It is often difficult to reuse or integrate models or their components, in part because they are not modular. Modular components allow the modeler to think more deeply about the role of the model and to more completely address a modeling project's requirements. In particular, modularity facilitates component reuse and model integration for models with different use cases, including the ability to exchange modules during or between simulations. The heterogeneous nature of biology and vast range of wet-lab experimental platforms call for modular models designed to satisfy a variety of use cases. We argue that software analogs of biological mechanisms are reasonable candidates for modularization. Biomimetic software mechanisms comprised of physiomimetic mechanism modules offer benefits that are unique or especially important to multi-scale, biomedical modeling and simulation. RESULTS: We present a general, scientific method of modularizing mechanisms into reusable software components that we call physiomimetic mechanism modules (PMMs). PMMs utilize parametric containers that partition and expose state information into physiologically meaningful groupings. To demonstrate, we modularize four pharmacodynamic response mechanisms adapted from an in silico liver (ISL). We verified the modularization process by showing that drug clearance results from in silico experiments are identical before and after modularization. The modularized ISL achieves validation targets drawn from propranolol outflow profile data. In addition, an in silico hepatocyte culture (ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The ISHC achieves validation targets drawn from propranolol intrinsic clearance data exhibiting considerable between-lab variability. The data used as validation targets for PMMs originate from both in vitro to in vivo experiments exhibiting large fold differences in time scale. CONCLUSIONS: This report demonstrates the feasibility of PMMs and their usefulness across multiple model use cases. The pharmacodynamic response module developed here is robust to changes in model context and flexible in its ability to achieve validation targets in the face of considerable experimental uncertainty. Adopting the modularization methods presented here is expected to facilitate model reuse and integration, thereby accelerating the pace of biomedical research. PMID- 25123170 TI - Impact of dairy consumption on essential hypertension: a clinical study. AB - BACKGROUND: Several studies have presented evidence suggesting that dairy consumption has beneficial effects on blood pressure (BP) in healthy subjects; however, only a few studies have examined this possibility in patients with established essential hypertension using ambulatory blood pressure monitoring. The objective of this study was to investigate how consuming dairy products impacts mean daytime systolic and diastolic BP in men and women with mild to moderate essential hypertension. METHODS: Eighty-nine men and women with systolic BP >= 135 mm Hg and <= 160 mm Hg and diastolic BP <= 110 mm Hg were enrolled in this single-blind, randomized, cross-over, controlled study. Participants had to incorporate three daily servings of dairy products or control products equivalent in macronutrients and sodium during four-week treatment phases. Twenty-four hour ambulatory BP and endothelial function were assessed at screening and at the end of each dietary phase. RESULTS: The consumption of three daily servings of dairy products led to a significant reduction in mean daytime ambulatory systolic BP ( 2 mm Hg; P = 0.05) in men compared with readings after the control phase. In women, dairy consumption had no effect on ambulatory systolic BP. Moreover, endothelial function was significantly improved by dairy consumption in the whole cohort. CONCLUSION: These data indicate that the consumption of three daily servings of dairy products have beneficial effects on daytime systolic ambulatory BP compared to a heart-healthy, dairy-free, diet in men with mild to moderate essential hypertension. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov as NCT01776216. PMID- 25123171 TI - Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats. AB - Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. PMID- 25123172 TI - Protocol for a randomized, placebo-controlled, double-blind clinical trial investigating sacral neuromodulation for neurogenic lower urinary tract dysfunction. AB - BACKGROUND: Sacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction, but its value in patients with a neurological cause is unclear. Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction, the number of investigated patients is low and there is a lack of randomized controlled trials. METHODS AND DESIGN: This study is a prospective, randomized, placebo-controlled, double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction are enrolled. After minimally invasive bilateral tined lead placement into the sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation testing for 3-6 weeks. In case of successful (defined as improvement of at least 50% in key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to baseline values) prolonged sacral neuromodulation testing, the neuromodulator is implanted in the upper buttock. After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation, the patients are randomized in a 1:1 allocation in sacral neuromodulation ON or OFF. At the end of the 2 months double-blind sacral neuromodulation phase, the patients have a neuro-urological re-evaluation, unblinding takes place, and the neuromodulator is turned ON in all patients. The primary outcome measure is success of sacral neuromodulation, secondary outcome measures are adverse events, urodynamic parameters, questionnaires, and costs of sacral neuromodulation. DISCUSSION: It is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for patients with refractory neurogenic lower urinary tract dysfunction. If this type of treatment is effective in the neurological population, it would revolutionize the management of neurogenic lower urinary tract dysfunction. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov; Identifier: NCT02165774. PMID- 25123173 TI - Cannabinoid-mediated short-term plasticity in hippocampus. AB - Endocannabinoids (eCBs) modulate both excitatory and inhibitory neurotransmission in hippocampus via activation of pre-synaptic cannabinoid receptors. Here, we present a model for cannabinoid mediated short-term depression of excitation (DSE) based on our recently developed model for the equivalent phenomenon of suppressing inhibition (DSI). Furthermore, we derive a simplified formulation of the calcium-mediated endocannabinoid synthesis that underlies short-term modulation of neurotransmission in hippocampus. The simplified model describes cannabinoid-mediated short-term modulation of both hippocampal inhibition and excitation and is ideally suited for large network studies. Moreover, the implementation of the simplified DSI/DSE model provides predictions on how both phenomena are modulated by the magnitude of the pre-synaptic cell's activity. In addition we demonstrate the role of DSE in shaping the post-synaptic cell's firing behaviour qualitatively and quantitatively in dependence on eCB availability and the pre-synaptic cell's activity. Finally, we explore under which conditions the combination of DSI and DSE can temporarily shift the fine balance between excitation and inhibition. This highlights a mechanism by which eCBs might act in a neuro-protective manner during high neural activity. PMID- 25123174 TI - Magnetic resonance imaging in patients with unilateral bloody nipple discharge; useful when conventional diagnostics are negative? AB - BACKGROUND: Unilateral bloody nipple discharge (UBND) is mostly caused by benign conditions such as papilloma or ductal ectasia. However, in 7-33 % of all nipple discharge, it is caused by breast cancer. Conventional diagnostic imaging like mammography (MMG) and ultrasonography (US) is performed to exclude malignancy. Preliminary investigations of breast magnetic resonance imaging (MRI) assume that it has additional value. With an increasing availability of MRI, it is of clinical importance to evaluate this. We evaluated the additional diagnostic value of MRI in patients with UBND in the absence of a palpable mass, with normal conventional imaging. METHODS: All women with UBND in the period November 2007 July 2012 were included. In addition to the standard work-up (patient's history, physical examination, MMG, and US), MRI was performed. Data from these examinations and treatment were collected retrospectively. RESULTS: A total of 111 women (mean age 52 years; range 23-80) were included. In nine (8 %) patients, malignancy was suspected on MRI while conventional imaging was normal. In eight (89 %) of these patients, histology was obtained, two by core biopsy and six by terminal duct excision. Benign conditions were found in six patients (86 %) and a (pre-) malignant lesion in two patients. In both cases, it concerned a ductal carcinoma in situ, which was treated with breast-conserving therapy. Moreover, in two cases of (pre)malignancy, the MRI was interpreted as negative. CONCLUSION: In patients with UBND who show no signs of a malignancy on conventional diagnostic examinations, the added value of a breast MRI is limited, since a malignancy can be demonstrated in <2 %. PMID- 25123175 TI - Early postoperative small bowel obstruction is an independent risk factor for subsequent adhesive small bowel obstruction in patients undergoing open colectomy. AB - BACKGROUND: This prospective study was performed to investigate whether postoperative ileus (POI) or early postoperative small bowel obstruction (EPSBO) affects the development of adhesive small bowel obstruction (SBO) in patients undergoing colectomy. METHODS: We prospectively enrolled 1,002 patients who underwent open colectomy by a single surgeon. POI was defined as the absence of bowel function for more than 5 days or as a delay in oral intake beyond 7 days postoperatively. EPSBO was defined as the clinical and radiologic identification of SBO after resuming oral intake between postoperative days 7 and 30. Adhesive SBO was defined as SBO developing after 30 days because of intraperitoneal adhesion. The associations between POI, EPSBO, patient- and surgery-related variables, and the development of adhesive SBO were analyzed. RESULTS: A total of 85 (8.5 %) patients developed POI, and 42 patients (4.2 %) developed EPSBO, with seven patients experiencing both POI and EPSBO. During the follow-up period (median 51 months), 70 patients (7.0 %) developed adhesive SBO, six (8.6 %) of whom needed laparotomy. The occurrence of adhesive SBO was significantly higher in patients with EPSBO than in those without EPSBO (26.5 vs. 7.5 % at 5 years, P < 0.001), but not in patients with POI (13.4 vs. 7.8 % at 5 years, P = 0.158). Multivariable analysis showed colostomy (hazard ratio [HR] 2.530, P = 0.006) and EPSBO (HR 4.063, P < 0.001) as independent risk factors for adhesive SBO. CONCLUSIONS: The development of adhesive SBO after colectomy is more frequent in patients with EPSBO and colostomy; however, POI does not increase the risk of adhesive SBO. PMID- 25123176 TI - Clinical significance of anatomical variant of the left hepatic artery for perihilar cholangiocarcinoma applied to right-sided hepatectomy. AB - BACKGROUND: Full understanding of the hilar anatomy is crucial for successful surgical resection of perihilar cholangiocarcinoma (PHC). METHODS: The three dimensional positional relationship between the left hepatic artery (LHA) and the umbilical portion of the left portal vein (UP) was evaluated using multidetector row computed tomography (CT) in 58 consecutive patients who underwent right-sided hepatectomy for Bismuth-Corlette IIIa or IV tumors. The positional relationship of the LHA related to UP was classified into the following three types: L-UP type, LHA runs into the left lateral section (LLS) from the left caudal side of the UP; R-UP type, LHA runs into the LLS from the right cranial side of the UP; and combined type, one branch of the LHA runs into the LLS from the right cranial side of the UP, and the other from the left caudal side of the UP. RESULTS: L-UP type LHA was observed in 53 cases (91.4 %), R-UP type in three cases (5.2 %), and combined type in two cases (3.4 %). No cancer involvement of the LHA was seen in any cases with L-UP type. In one case with R-UP type (one of three; 33.3 %) and one case with combined type (one of two, 50 %), cancer invasion to the LHA was observed at the right side of the UP, requiring combined resection of the involved LHA. CONCLUSIONS: R-UP-type LHA running just along the left hepatic duct may be easily involved by right-side predominant PHC when extending to the left hepatic duct. Hepatobiliary surgeons should recognize this anatomical variant and carefully evaluate the running courses of LHA to successfully perform R0 resection in right-sided hepatectomy for PHC. PMID- 25123177 TI - The pathologic correlation between liver and portal vein invasion in perihilar cholangiocarcinoma: evaluating the oncologic rationale for the American Joint Committee on Cancer definitions of T2 and T3 tumors. AB - BACKGROUND: The American Joint Committee on Cancer (AJCC) has recommended that cancers with liver involvement be graded T2b and those with portal vein involvement be graded T3, although the value of staging as prognostic factors remains unclear. We evaluated the current definition of the T2/3 tumors for perihilar cholangiocarcinoma. METHODS: A total of 202 patients with perihilar cholangiocarcinoma who underwent hepatectomy without vascular resection were enrolled. Clinicopathologic data about invasion of the liver and the unilateral portal vein were evaluated. RESULTS: The liver and the unilateral portal vein were involved in 100 (49.5 %) and 38 (18.8 %) patients, respectively. The survival rates were not significantly different between patients with and without liver invasion (48.6 vs. 52.2 %, respectively, at 5 years, P = 0.157) and between patients with or without unilateral portal vein invasion (43.2 vs. 52.1 %, respectively, at 5 years, P = 0.363). The survival rate of patients with tumors staged pT2b was not significantly different from the rate of patients with pT2a (63.4 vs. 55.6 % at 5 years, P = 0.912), and the pT2b tumor patient survival rate was better than the rate of patients with pT3 (34.9 % at 5 years, P = 0.011). Using multivariate analysis, nodal metastasis (P = 0.003), positive surgical margin (P = 0.010), and Bismuth type IV tumor (P = 0.039) were identified as independent prognostic factors. CONCLUSIONS: The liver and the unilateral portal vein are frequently involved in perihilar cholangiocarcinoma. The determinants of the current AJCC T2/3 tumor classifications are rational; however, subdivision of T2 tumors may be of less clinical value. PMID- 25123179 TI - The effect of Doppler ultrasound on early vascular interventions and clinical outcomes after liver transplantation. AB - BACKGROUND: During the immediate postoperative period after liver transplantation (LT), postoperative bleeding and vascular complications (stenosis, thrombosis) are the two most common complications that require therapeutic decisions. Doppler ultrasound (DUS) is the established method for screening vascular patency after LT during the immediate postoperative period. The objective of our study was to evaluate the impact of DUS performed on postoperative days (POD) 1 and 2 on early vascular interventions. METHODS: We studied 200 patients who had undergone living donor or deceased donor liver transplantation between January 2011 and March 2012. Postoperative liver DUS findings of up to POD 14, including patency of hepatic artery, portal vein, and hepatic vein, were retrieved. Patients with normal DUS findings on POD 1 and POD 2 were classified as the normal early DUS group. Patients with abnormal DUS findings at POD1 or POD2 were classified as the abnormal early DUS group. Frequency of vascular interventions was compared between the two groups. Risk factors that predict vascular interventions also were assessed. RESULTS: On POD 1 and 2, 81.5 % (163/200) had normal DUS findings and management was not altered by subsequent DUS findings. Two patients in the normal group were found to have hepatic artery dissection and hepatic vein thrombosis on routine CT on POD 7 and received vascular intervention. DUS results in the two patients were normal until POD 6, but DUS performed after the CT on POD 7 were consistent with the CT findings. Of the 37 recipients who showed abnormal DUS findings on POD 1 or 2, the DUS findings were normalized or unchanged thereafter in 33 patients and no vascular interventions were performed. Two patients underwent hepatic artery thrombectomy on POD 2, one patient required a portal vein thrombectomy on POD 1, and one patient died on POD 3 due to bleeding. The overall incidence of vascular complication requiring vascular interventions was 2.5 %. Logistic regression identified abnormal DUS findings on POD 1 or 2 as an independent risk factor of vascular complications requiring intervention. CONCLUSIONS: In LT recipients who demonstrate normal DUS findings in the first 2 postoperative days, additional DUS screening may have value only when clinically indicated. PMID- 25123180 TI - Enhanced recovery programs in liver surgery. PMID- 25123181 TI - Preventing inguinodynia after hernia surgery: does the type of mesh matter? PMID- 25123182 TI - Moderate intra-abdominal free fluid on computed tomogram in patients with blunt trauma abdomen: time to shun non-operative approach. PMID- 25123184 TI - Epigalloccatechin-3-gallate inhibits ocular neovascularization and vascular permeability in human retinal pigment epithelial and human retinal microvascular endothelial cells via suppression of MMP-9 and VEGF activation. AB - Epigalloccatechin-3-gallate (EGCG) is the main polyphenol component of green tea (leaves of Camellia sinensis). EGCG is known for its antioxidant, anti inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play a key role in the processes of extracellular matrix (ECM) remodeling and microvascular permeability during angiogenesis. We investigated the inhibitory effects of EGCG on ocular neovascularization and vascular permeability using the retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG treatment significantly decreased mRNA and protein expression levels of MMP-9 in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor alpha (TNF-alpha) in human retinal pigment epithelial cells (HRPECs). EGCG also effectively protected ARPE-19 cells from cell death and attenuated mRNA expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2) by inhibiting generation of reactive oxygen species (ROS). EGCG significantly inhibited proliferation, vascular permeability, and tube formation in VEGF induced human retinal microvascular endothelial cells (HRMECs). Furthermore, EGCG significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models. In addition, EGCG effectively limited upregulation of MMP-9 and platelet endothelial cell adhesion molecule (PECAM/CD31) on corneal neovascularization (CNV) induced by alkaline burn. Our data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for treatment and prevention of ocular angiogenic diseases such as age-related macular degeneration, diabetic retinopathy, and corneal neovascularization. PMID- 25123186 TI - The effect of some fluoroquinolone family members on biospeciation of copper(II), nickel(II) and zinc(II) ions in human plasma. AB - The speciation of Cu2+, Ni2+ and Zn2+ ions in the presence of the fluoroquinolones (FQs) moxifloxacin, ofloxacin, levofloxacin and ciprofloxacin, in human blood plasma was studied under physiological conditions by computer simulation. The speciation was calculated using an updated model of human blood plasma including over 6,000 species with the aid of the program Hyss2009. The identity and stability of metal-FQ complexes were determined by potentiometric (310 K, 0.15 mol/L NaCl), spectrophotometric, spectrofluorimetric, ESI-MS and 1H NMR measurements. In the case of Cu2+ ion the concentration of main low molecular weight (LMW) plasma complex (Cu(Cis)His) is very slightly influenced by all examined FQs. FQs show much higher influence on main plasma Ni2+ and Zn2+ complexes: (Ni(His)2 and Zn(Cys)Cit, respectively. Levofloxacin exhibits the highest influence on the fraction of the main nickel complex, Ni(His)2, even at a concentration level of 3*10-5 mol/L. The same effect is seen on the main zinc complex, Zn(Cys)Cit. Calculated plasma mobilizing indexes indicate that ciprofloxacin possesses the highest mobilizing power from plasma proteins, toward copper ion, while levofloxacin is the most influential on nickel and zinc ions. The results obtained indicate that the drugs studied are safe in relation to mobilization of essential metal ions under physiological conditions. The observed effects were explained in terms of competitive equilibrium reactions between the FQs and the main LMW complexes of the metal ions. PMID- 25123187 TI - Tryptophan as a probe to study the anticancer mechanism of action and specificity of alpha-helical anticancer peptides. AB - In the present study, a single tryptophan, as a fluorescence probe, was shifted from the N-terminus to the middle and to the C-terminus of a 26-residue alpha helical anticancer peptide sequence to study the mechanism of action and specificity. The hydrophobicity of peptides, as well as peptide helicity and self associating ability, were slightly influenced by the position change of tryptophan in the peptide sequence, while the hemolytic activity and anticancer activity of the peptide analogs remained the same. The tryptophan fluorescence experiment demonstrated that peptide analogs were more selective against LUVs mimicking cancer cell membranes than LUVs mimicking normal cell membranes. During the interaction with target membranes, the N-terminus of an anticancer peptide may be inserted vertically or tilted into the hydrophobic components of the phospholipid bilayer first. The thermodynamic parameters of the peptides PNW and PCW, when interacting with zwitterionic DMPC or negatively charged DMPS, were determined by ITC. DSC experiments showed that peptide analogs significantly altered the phase transition profiles of DMPC, but did not dramatically modify the phase transition of DMPS. It is demonstrated that hydrophobic interactions are the main driving force for peptides interacting with normal cell membranes, whilst, electrostatic interactions dominate the interactions between peptides and cancer cell membranes. Utilizing tryptophan as a fluorescence probe molecule appears to be a practicable approach to determine the interaction of peptides with phospholipid bilayers. PMID- 25123185 TI - Effect on the aroma profile of Graciano and Tempranillo red wines of the application of two antifungal treatments onto vines. AB - The effect of two antifungals (boscalid+kresoxim-methyl and metrafenone) applied onto vines under Good Agricultural Practices (GAPs) on the volatile composition of Tempranillo and Graciano red wines was studied. Changes in aroma profile in the wines were assessed from the combined odour activity values (OAVs) for the volatile compounds in each of seven different odorant series (viz., ripe fruits, fresh fruits, lactic, floral, vinous, spicy and herbaceous). Graciano wines obtained from grapes treated with the antifungals exhibited markedly increased concentrations of varietal volatile compounds (monoterpenes and C13 norisoprenoids) and aldehydes, and decreased concentrations of acetates and aromatic alcohols. By contrast, the concentrations of volatile compounds in Tempranillo wines showed different changes depending on the fungicide applied. Also, the aroma profiles of wines obtained from treated grapes were modified, particularly the ripe fruit nuances in Graciano wines. The OAV of this odorant series underwent an increase by more than 60% with respect to the control wine as a result of the increase of beta-damascenone concentration (which imparts wine a dry plum note). The aroma profile of Tempranillo red wines containing metrafenone residues exhibited marked changes relative to those from untreated grapes. PMID- 25123188 TI - The toxicity mechanisms of action of Abeta25-35 in isolated rat cardiac myocytes. AB - beta-Amyloid (Abeta) is deposited in neurons and vascular cells of the brain and is characterized as a pathologic feature of Alzheimer's disease (AD). Recently studies have reported that there is an association between cardiovascular risk factors and AD, however the mechanism of this association is still uncertain. In this study we observed Abeta had an effect on cardiovascular cells. We represent as a major discovery that Abeta25-35 had toxicity on isolated rat cardiac myocytes by impacting the cytoskeleton assembly and causing ER stress, ultimately contributing to the apoptosis of the myocytes. Importantly, the activation of ER stress and subsequent cellular dysfunction and apoptosis by Abeta25-35 was regulated by the MAPK pathway, which could be prevented by inhibition of p38 via pharmacological inhibitors. It was noteworthy that Abeta25-35 played a critical role in cardiac myocytes, suggesting that Alzheimer's disease (AD) had a relation with the heart and understanding of these associations in future will help search for effective treatment strategies. PMID- 25123183 TI - Imaging live cells at the nanometer-scale with single-molecule microscopy: obstacles and achievements in experiment optimization for microbiology. AB - Single-molecule fluorescence microscopy enables biological investigations inside living cells to achieve millisecond- and nanometer-scale resolution. Although single-molecule-based methods are becoming increasingly accessible to non experts, optimizing new single-molecule experiments can be challenging, in particular when super-resolution imaging and tracking are applied to live cells. In this review, we summarize common obstacles to live-cell single-molecule microscopy and describe the methods we have developed and applied to overcome these challenges in live bacteria. We examine the choice of fluorophore and labeling scheme, approaches to achieving single-molecule levels of fluorescence, considerations for maintaining cell viability, and strategies for detecting single-molecule signals in the presence of noise and sample drift. We also discuss methods for analyzing single-molecule trajectories and the challenges presented by the finite size of a bacterial cell and the curvature of the bacterial membrane. PMID- 25123189 TI - Intracellular diagnostics: hunting for the mode of action of redox-modulating selenium compounds in selected model systems. AB - Redox-modulating compounds derived from natural sources, such as redox active secondary metabolites, are currently of considerable interest in the field of chemoprevention, drug and phytoprotectant development. Unfortunately, the exact and occasionally even selective activity of such products, and the underlying (bio-)chemical causes thereof, are often only poorly understood. A combination of the nematode- and yeast-based assays provides a powerful platform to investigate a possible biological activity of a new compound and also to explore the "redox link" which may exist between its activity on the one side and its chemistry on the other. Here, we will demonstrate the usefulness of this platform for screening several selenium and tellurium compounds for their activity and action. We will also show how the nematode-based assay can be used to obtain information on compound uptake and distribution inside a multicellular organism, whilst the yeast-based system can be employed to explore possible intracellular mechanisms via chemogenetic screening and intracellular diagnostics. Whilst none of these simple and easy-to-use assays can ultimately substitute for in-depth studies in human cells and animals, these methods nonetheless provide a first glimpse on the possible biological activities of new compounds and offer direction for more complicated future investigations. They may also uncover some rather unpleasant biochemical actions of certain compounds, such as the ability of the trace element supplement selenite to induce DNA strand breaks. PMID- 25123190 TI - [Quality of life after operation for early Barrett's cancer: a prospective comparison of Ivor Lewis resection versus modified Merendino resection]. PMID- 25123193 TI - I want to fly home: a terminal cancer patient's right to go home. PMID- 25123192 TI - Changes in medication profile among patients with advanced cancer admitted to an acute palliative care unit. AB - PURPOSE: The decision-making process for medication use in the last weeks of life is complex because of patient frailty and poor prognosis. Limited literature is available on medication use in the palliative care setting, particularly in acute palliative care units (APCUs). We examined the changes in medication profile among hospitalized patients with advanced cancer before their palliative care inpatient consultation team referral, after palliative care consultation, at the time of APCU admission, and at APCU discharge or death. METHODS: We included consecutive patients with advanced cancer who were first seen by our inpatient palliative care consultation team and subsequently admitted to the APCU. We retrieved data on all scheduled medications at the prespecified time points. RESULTS: Among the 100 patients, the median duration of hospitalization was 10.5 days (interquartile range 8-15 days), and the median APCU stay was 5 days (interquartile range 3-7 days). The average number of medications before palliative care inpatient consultation team referral, after palliative care consultation, at APCU admission and at APCU discharge/death was 9.2 (standard deviation [SD] 4.5), 9.9 (SD 4.2), 10.3 (SD 3.8), and 10.1 (SD 3.8), respectively (P = 0.03). An increasing proportion of patients received medications for symptom control over their course of hospitalization, including systemic corticosteroids, laxatives, neuroleptics, and antiulcer agents (P < 0.05). In contrast, the frequency of several classes of medications such as antihypertensives, antilipemics, and anticonvulsants decreased over time (P < 0.05). CONCLUSIONS: Palliative care involvement was associated with an increase in symptom control medications and decrease in medications for comorbid conditions over time. PMID- 25123191 TI - Deep sequencing reveals clonal evolution patterns and mutation events associated with relapse in B-cell lymphomas. AB - BACKGROUND: Molecular mechanisms associated with frequent relapse of diffuse large B-cell lymphoma (DLBCL) are poorly defined. It is especially unclear how primary tumor clonal heterogeneity contributes to relapse. Here, we explore unique features of B-cell lymphomas - VDJ recombination and somatic hypermutation - to address this question. RESULTS: We performed high-throughput sequencing of rearranged VDJ junctions in 14 pairs of matched diagnosis-relapse tumors, among which 7 pairs were further characterized by exome sequencing. We identify two distinctive modes of clonal evolution of DLBCL relapse: an early-divergent mode in which clonally related diagnosis and relapse tumors diverged early and developed in parallel; and a late-divergent mode in which relapse tumors developed directly from diagnosis tumors with minor divergence. By examining mutation patterns in the context of phylogenetic information provided by VDJ junctions, we identified mutations in epigenetic modifiers such as KMT2D as potential early driving events in lymphomagenesis and immune escape alterations as relapse-associated events. CONCLUSIONS: Altogether, our study for the first time provides important evidence that DLBCL relapse may result from multiple, distinct tumor evolutionary mechanisms, providing rationale for therapies for each mechanism. Moreover, this study highlights the urgent need to understand the driving roles of epigenetic modifier mutations in lymphomagenesis, and immune surveillance factor genetic lesions in relapse. PMID- 25123194 TI - Unanticipated frequency and consequences of regimen-related diarrhea in patients being treated with radiation or chemoradiation regimens for cancers of the head and neck or lung. AB - PURPOSE: To better understand the indirect effects of standard courses of radiation therapy (RT) on distant tissue toxicity, we evaluated the frequency, course, and health and economic burden of regimen-related diarrhea in a large, multinational group of patients who were being treated for cancers of the head and neck (HNC) or lung (NSCLC). METHODS: In this exploratory, prospective study, 284 patients being treated for HNC and 60 being treated for NSCLC were stratified into four cohorts to evaluate the effect of radiation alone and radiation plus concomitant chemotherapy (CRT) on radiation-induced diarrhea (RID). RID was assessed daily throughout RT using a patient-reported five-point categorical scale. Health and resource use outcomes were evaluated at least weekly during radiation. RESULTS: Moderate to severe RID was reported in all groups and was worse among patient being treated with concomitant chemoradiation (CRT). Whereas 29 % of patients treated with radiation only developed RID, the incidence was 42 % among CRT-treated patients. Tumor site did not impact the rate of RID, but did impact the rate of development and was more acute in patients being treated for NSCLC than for HNC. Patients with significant RID had worse health and resource use outcomes than did patients without RID regardless of the form of treatment. G tube placement, weight loss, unplanned office visits, and in-patient days were adversely affected by RID. Not surprisingly, patients treated with CRT had poorer health and resource outcomes than RT only patients, even in the absence of RID. CONCLUSION: In addition to local tissue toxicities, our results suggest that focal radiation may also be associated with significant distant tissue-centric injury here represented by RID. While these changes were seen with radiation alone, the addition of chemotherapy increased the incidence and burden of illness. RID adversely impacted resource use. This unanticipated finding supports the hypothesis that focal radiation therapy results in pathobiological changes that extend beyond the radiation field and which can produce distant changes. PMID- 25123195 TI - Ligand-size dependent water proton relaxivities in ultrasmall gadolinium oxide nanoparticles and in vivo T1 MR images in a 1.5 T MR field. AB - The dependence of longitudinal (r1) and transverse (r2) water proton relaxivities of ultrasmall gadolinium oxide (Gd2O3) nanoparticles on the surface coating ligand-size was investigated. Both r1 and r2 values decreased with increasing ligand-size. We attributed this to the ligand-size effect. In addition the effectiveness of d-glucuronic acid-coated ultrasmall Gd2O3 nanoparticles as T1 magnetic resonance imaging (MRI) contrast agents was confirmed by measuring the in vitro cytotoxicity and using in vivo T1 MR images in a mouse in a 1.5 T MR field. PMID- 25123196 TI - Caffeine consumption around an exercise bout: effects on energy expenditure, energy intake, and exercise enjoyment. AB - Combining an exercise and nutritional intervention is arguably the optimal method of creating energy imbalance for weight loss. This study sought to determine whether combining exercise and caffeine supplementation was more effective for promoting acute energy deficits and manipulations to substrate metabolism than exercise alone. Fourteen recreationally active participants (mean +/- SD body mass index: 22.7 +/- 2.6 kg/m2) completed a resting control trial (CON), a placebo exercise trial (EX), and a caffeine exercise trial (EX+CAF, 2 * 3 mg/kg of caffeine 90 min before and 30 min after exercise) in a randomized, double blinded design. Trials were 4 h in duration with 1 h of rest, 1 h of cycling at ~65% power at maximum O2 consumption or rest, and a 2-h recovery. Gas exchange, appetite perceptions, and blood samples were obtained periodically. Two hours after exercise, participants were offered an ad libitum test meal where energy and macronutrient intake were recorded. EX+CAF resulted in significantly greater energy expenditure and fat oxidation compared with EX (+250 kJ; +10.4 g) and CON (+3,126 kJ; +29.7 g) (P < 0.05). A trend for reduced energy and fat intake compared with CON (-718 kJ; -8 g) (P = 0.055) was observed. Consequently, EX+CAF created a greater energy deficit (P < 0.05). Caffeine also led to exercise being perceived as less difficult and more enjoyable (P < 0.05). Combining caffeine with exercise creates a greater acute energy deficit, and the implications of this protocol for weight loss or maintenance over longer periods of time in overweight/obese populations should be further investigated. PMID- 25123197 TI - Hemodynamic responses during graded and constant-load plantar flexion exercise in middle-aged men and women with type 2 diabetes. AB - We tested the hypotheses that type 2 diabetes (T2D) impairs the 1) leg hemodynamic responses to an incremental intermittent plantar-flexion exercise and 2) dynamic responses of leg vascular conductance (LVC) during low-intensity (30% maximal voluntary contraction, MVC) and high-intensity (70% MVC) constant-load plantar-flexion exercise in the supine posture. Forty-four middle-aged individuals with T2D (14 women), and 35 healthy nondiabetic (ND) individuals (18 women) were tested. Leg blood flow (LBF) was measured between each contraction using venous occlusion plethysmography. During the incremental test peak force (Fpeak) relative to MVC was significantly reduced (P < 0.05) in men and women with T2D compared with their respective nondiabetic counterparts. Peak LBF and the slope of LBF relative to percentage Fpeak were also reduced (P < 0.05) in women with T2D compared with healthy women (peak blood flow, 460.6 +/- 126.8 vs. 628.3 +/- 347.7 ml/min; slope, 3.78 +/- 1.74 vs. 5.85 +/- 3.14 ml.min(-1).%Fpeak (-1)) and in men with T2D compared with nondiabetic men (peak blood flow, 621.7 +/- 241.3 vs. 721.2 +/- 359.7 ml/min; slope, 5.75 +/- 2.66 vs. 6.33 +/- 3.63 ml.min(-1).%Fpeak (-1)). During constant-load contractions at 30% MVC T2D did not affect the dynamic responses of LVC (LBF/MAP). However, at 70% MVC [completed by a subgroup of participants (20 with T2D, 6 women; 13 ND, 6 women)] the time constant of the second growth phase of LVC was longer and the amplitude of the first growth phase was lower (P < 0.05 for both) in men and women with T2D. The results suggest that the T2D-induced impairments in performance of the leg muscles are related to reductions in blood flow in both men and women. PMID- 25123198 TI - Acute effects of taurine on sarcoplasmic reticulum Ca2+ accumulation and contractility in human type I and type II skeletal muscle fibers. AB - Taurine occurs in high concentrations in muscle and is implicated in numerous physiological processes, yet its effects on many aspects of contractility remain unclear. Using mechanically skinned segments of human vastus lateralis muscle fibers, we characterized the effects of taurine on sarcoplasmic reticulum (SR) Ca2+ accumulation and contractile apparatus properties in type I and type II fibers. Prolonged myoplasmic exposure (>10 min) to taurine substantially increased the rate of accumulation of Ca2+ by the SR in both fiber types, with no change in the maximum amount accumulated; no such effect was found with carnosine. SR Ca2+ accumulation was similar with 10 or 20 mM taurine, but was significantly slower at 5 mM taurine. Cytoplasmic taurine (20 mM) had no detectable effects on the responsiveness of the Ca2+ release channels in either fiber type. Taurine caused a small increase in Ca2+ sensitivity of the contractile apparatus in type I fibers, but type II fibers were unaffected; maximum Ca(2+)-activated force was unchanged in both cases. The effects of taurine on SR Ca2+ accumulation (1) only became apparent after prolonged cytoplasmic exposure, and (2) persisted for some minutes after complete removal of taurine from the cytoplasm, consistent with the hypothesis that the effects were due to an action of taurine from inside the SR. In summary, taurine potentiates the rate of SR Ca2+ uptake in both type I and type II human fibers, possibly via an action from within the SR lumen, with the degree of potentiation being significantly reduced at low physiological taurine levels. PMID- 25123199 TI - Quantitative and temporal differential recovery of articular and muscular limitations of knee joint contractures; results in a rat model. AB - Joint contractures alter the mechanical properties of articular and muscular structures. Reversibility of a contracture depends on the restoration of the elasticity of both structures. We determined the differential contribution of articular and muscular structures to knee flexion contractures during spontaneous recovery. Rats (250, divided into 24 groups) had one knee joint surgically fixed in flexion for six different durations, from 1 to 32 wk, creating joint contractures of various severities. After the fixation was removed, the animals were left to spontaneously recover for 1 to 48 wk. After the recovery periods, animals were killed and the knee extension was measured before and after division of the transarticular posterior muscles using a motorized arthrometer. No articular limitation had developed in contracture of recent onset (<=2 wk of fixation, P > 0.05); muscular limitations were responsible for the majority of the contracture (34 +/- 8 degrees and 38 +/- 6 degrees , respectively; both P < 0.05). Recovery for 1 and 8 wk reversed the muscular limitation of contractures of recent onset (1 and 2 wk of fixation, respectively). Long-lasting contractures (>=4 wk of fixation) presented articular limitations, irreversible in all 12 durations of recovery compared with controls (all 12 P < 0.05). Knee flexion contractures of recent onset were primarily due to muscular structures, and they were reversible during spontaneous recovery. Long-lasting contractures were primarily due to articular structures and were irreversible. Comprehensive temporal and quantitative data on the differential reversibility of mechanically significant alterations in articular and muscular structures represent novel evidence on which to base clinical practice. PMID- 25123200 TI - Cardiovascular and thermoregulatory biomarkers of heat stroke severity in a conscious rat model. AB - Multiorgan failure is a catastrophic consequence of heat stroke (HS) and considered the underlying etiology of mortality. Identifying novel biomarkers capable of predicting the extent of HS-induced organ damage will enhance point-of care triage and treatment. Conscious male F344 rats (n = 32) were radiotelemetered for continuous core temperature (Tc), heart rate, and arterial pressure measurement. Twenty-two animals were exposed to ambient temperature of 37 degrees C to a maximum Tc of 41.9 +/- 0.1 degrees C. Rats were euthanized at 24 h of recovery for analysis of plasma biomarkers [cardiac troponin I (cTnI), blood urea nitrogen (BUN), alanine aminotransferase (ALT), albumin, glucose] and histology. Tc profiles observed during recovery stratified HS severity into Mild, Moderate, and Severe. Eleven (50%) animals exhibited an acute compensatory hemodynamic response to heat exposure and a monophasic Tc profile consisting of sustained hyperthermia (~1 degrees C). Five (23%) rats displayed hemodynamic challenge and a biphasic Tc profile with rapid return to baseline followed by rebound hyperthermia. All biomarkers were significantly altered from control values (P < 0.05). Four (18%) animals exhibited significant hemodynamic compromise during heat and a triphasic profile characterized by rapid cooling to baseline Tc, rebound hyperthermia, and subsequent hypothermia (~35 degrees C) through 24 h. cTnI showed a 40-fold increase over CON (P < 0.001) and correlated with BUN (r = 0.912) consistent with cardiorenal failure. Hypoglycemia correlated with ALT (r = 0.824) suggestive of liver dysfunction. Histology demonstrated myocardial infarction, renal tubular necrosis, and acute liver necrosis. Two (9%) animals succumbed during HS recovery. This study identified novel biomarkers that predict HS severity and organ damage during acute recovery that could provide clinical significance for identifying key biomarkers of HS pathogenesis. PMID- 25123202 TI - Copper metal-organic framework nanocrystal for plane effect nonenzymatic electro catalytic activity of glucose. AB - This work describes the first demonstration of nanocrystal plane dependent nonenzymatic electro-catalytic glucose activity of [Cu3(btc)2] nanocrystals with different shapes (nanocube, truncated cube, cuboctahedron, and octahedron). From electrochemical results, the obtained [Cu3(btc)2] nanocube modified electrode shows the best nonenzymatic electro-catalytic glucose activity. Interestingly, decreasing the {100} crystal planes from cubes to octahedra, changes the nonenzymatic electro-catalytic activity from highly sensitive to general. PMID- 25123201 TI - Protective effect of sex on chronic stress- and depressive behavior-induced vascular dysfunction in BALB/cJ mice. AB - The presence of chronic, unresolvable stresses leads to negative health outcomes, including development of clinical depression/depressive disorders, with outcome severity being correlated with depressive symptom severity. One of the major outcomes associated with chronic stress and depression is the development of cardiovascular disease (CVD) and an elevated CVD risk profile. However, in epidemiological research, sex disparities are evident, with premenopausal women suffering from depressive symptoms more acutely than men, but also demonstrating a relative protection from the onset of CVD. Given this, we investigated the differential effect of sex on conduit artery and resistance arteriolar function in male and female mice following 8 wk of an unpredictable chronic mild stress (UCMS) protocol. In males, plasma cortisol and depressive symptom severity (e.g., coat status, anhedonia, delayed grooming) were elevated by UCMS. Endothelium dependent dilation to methacholine/acetylcholine was impaired in conduit arteries and skeletal muscle arterioles, suggesting a severe loss of nitric oxide bioavailability and increased production of thromboxane A2 vs. prostaglandin I2 associated with elevated reactive oxygen species (ROS) and an increased level of systemic inflammation. Endothelium-independent dilation was intact. In females, depressive symptoms and plasma cortisol increases were more severe than in males, although alterations to vascular reactivity were blunted, including the effects of elevated ROS and inflammation on dilator responses. These results suggest that compared with males, female rats are more susceptible to chronic stress in terms of the severity of depressive behaviors, but that the subsequent development of vasculopathy is blunted owing to an improved ability to tolerate elevated ROS and systemic inflammatory stress. PMID- 25123203 TI - Acute kidney injury after snakebite accident treated in a Brazilian tertiary care centre. AB - AIM: Acute kidney injury (AKI) is one of the main causes of morbidity and mortality in cases of envenomation by venomous snakes. The present study was carried out to investigate the clinical and laboratory manifestations in accidents with venomous snakes and the risk factors associated with AKI in these accidents. METHODS: A retrospective study was carried out with patients victims of snakebite admitted to a reference centre. AKI was defined according to the RIFLE and AKIN criteria. RESULTS: A total of 276 patients were included, of which 230 (83.7%) were males. AKI was observed in 42 cases (15.2%). The mean genus involved in the accidents was Bothrops (82.2%). Mean age of patients with AKI was higher than in patients without AKI (43 +/- 20 vs. 34 +/- 21 years, P = 0.015). The time elapsed between the accident and medical care was higher in the AKI group (25 +/- 28 vs. 14 +/- 16h, P = 0.034), as well as the time elapsed between the accident and the administration of antivenom (30.7 +/- 27 vs. 15 +/- 16 h, P = 0.01). Haemodialysis was required in 30% of cases and complete renal function recovery was observed in 54.8% of cases at hospital discharge. There were four deaths, none of which had AKI. Factors associated with AKI were haemorrhagic abnormalities (P = 0.036, OR = 6.718, 95% CI: 1.067-25.661) and longer length of hospital stay (P = 0.004, OR = 1.69, 95% CI 1.165-2.088). CONCLUSION: Acute kidney injury is an important complication of snakebite accidents, showing low mortality, but high morbidity, which can lead to partial renal function recovery. PMID- 25123204 TI - Protocol for the induction of subarachnoid hemorrhage in mice by perforation of the Circle of Willis with an endovascular filament. AB - Genetically engineered mice are a valuable tool to investigate the molecular and cellular mechanisms leading to brain damage following subarachnoid hemorrhage (SAH). Therefore, several murine SAH models were developed during the last 15 years. Among those models, the perforation of the Circle of Willis by an endovascular filament or "filament model" turned out to become the most popular one, since it is believed to reproduce some of the most prominent pathophysiological features observed after human SAH. Despite the importance of the endovascular filament model for SAH research, relatively few studies were published using this technique during the past years and a number of laboratories reported problems establishing the technique. This triggered discussions about the standardization, reproducibility, and the reliability of the model. In order to improve this situation, the current paper aims to provide a comprehensive hands-on protocol of the murine endovascular filament model. The protocol proved to result in induction of SAH in mice with high intrapersonal and interpersonal reproducibility and is based on our experience with this technique for more than 10 years. By sharing our experience with this valuable model, we aim to initiate a constantly ongoing discussion process on the improvement of standards and techniques in the field of experimental SAH research. PMID- 25123206 TI - Commentary: predictors of severe outcomes associated with Clostridium difficile infection in inflammatory bowel disease patients. PMID- 25123205 TI - Effects of childhood abuse on adult obesity: a systematic review and meta analysis. AB - Controversy exists surrounding the role of childhood abuse in obesity development. This is a meta-analysis of observational studies on the role of childhood abuse in adult obesity. Systematic searches of PubMed, PsycInfo, Medline and CINAHL resulted in 23 cohort studies (4 prospective, 19 retrospective) with n=112,708 participants, containing four abuse types (physical, emotional, sexual, general). Four studies reported dose-response effects. A random effects model was used to quantify effect sizes, meta regression/subgroup analysis for identifying potential moderating variables and Egger's test for publication bias. Adults who reported childhood abuse were significantly more likely to be obese (odds ratio [OR]: 1.34, 95% confidence interval [CI]: 1.24-1.45, P<0.001). All four types of abuse were significantly associated with adult obesity: physical (OR: 1.28, 95% CI: 1.13-1.46), emotional (OR: 1.36, 95% CI: 1.08-1.71), sexual (OR: 1.31, 95% CI: 1.13-1.53) and general abuse (OR: 1.45, 95% CI: 1.25-1.69). Severe abuse (OR: 1.50, 95% CI: 1.27-1.77) was significantly more associated with adult obesity (P=0.043) compared with light/moderate abuse (OR: 1.13, 95% CI: 0.91-1.41). We found no significant effects of study design (prospective vs. retrospective, P=0.07), age (P=0.96) or gender (P=0.92). Publication bias was evident (Egger's test P=0.007), but effect sizes remained statistically significant in sensitivity analyses. Childhood abuse was clearly associated with being obese as an adult, including a positive dose response association. This suggests that adverse life experiences during childhood plays a major role in obesity development, potentially by inducing mental and emotional perturbations, maladaptive coping responses, stress, inflammation and metabolic disturbances. PMID- 25123207 TI - Production and supply of high-quality food protein for human consumption: sustainability, challenges, and innovations. AB - The Food and Agriculture Organization of the United Nations estimates that 843 million people worldwide are hungry and a greater number suffer from nutrient deficiencies. Approximately one billion people have inadequate protein intake. The challenge of preventing hunger and malnutrition will become even greater as the global population grows from the current 7.2 billion people to 9.6 billion by 2050. With increases in income, population, and demand for more nutrient-dense foods, global meat production is projected to increase by 206 million tons per year during the next 35 years. These changes in population and dietary practices have led to a tremendous rise in the demand for food protein, especially animal source protein. Consuming the required amounts of protein is fundamental to human growth and health. Protein needs can be met through intakes of animal and plant source foods. Increased consumption of food proteins is associated with increased greenhouse gas emissions and overutilization of water. Consequently, concerns exist regarding impacts of agricultural production, processing and distribution of food protein on the environment, ecosystem, and sustainability. To address these challenging issues, the New York Academy of Sciences organized the conference "Frontiers in Agricultural Sustainability: Studying the Protein Supply Chain to Improve Dietary Quality" to explore sustainable innovations in food science and programming aimed at producing the required quality and quantity of protein through improved supply chains worldwide. This report provides an extensive discussion of these issues and summaries of the presentations from the conference. PMID- 25123208 TI - Clinical and economic outcomes of nutrition interventions across the continuum of care. AB - Optimal nutrition across the continuum of care plays a key role in the short- and long-term clinical and economic outcomes of patients. Worldwide, an estimated one quarter to one-half of patients admitted to hospitals each year are malnourished. Malnutrition can increase healthcare costs by delaying patient recovery and rehabilitation and increasing the risk of medical complications. Nutrition interventions have the potential to provide cost-effective preventive care and treatment measures. However, limited data exist on the economics and impact evaluations of these interventions. In this report, nutrition and health system researchers, clinicians, economists, and policymakers discuss emerging global research on nutrition health economics, the role of nutrition interventions across the continuum of care, and how nutrition can affect healthcare costs in the context of hospital malnutrition. PMID- 25123209 TI - Antibody-drug conjugates: an emerging modality for the treatment of cancer. AB - Antibody-drug conjugates (ADCs) offer promise as a therapeutic modality that can potentially reduce the toxicities and poor therapeutic indices caused by the lack of specificity of conventional anticancer therapies. ADCs combine the potency of cytotoxic agents with the target selectivity of antibodies by chemically linking a cytotoxic payload to an antibody, potentially creating a synthetic molecule that will deliver targeted antitumor therapy that is both safe and efficacious. The ADC repertoire contains a range of payload molecules, antibodies, and linkers. Two ADC molecules, Kadcyla(r) and Adcetris(r), have been approved by the FDA, and many more are currently in clinical development. PMID- 25123211 TI - Architecture and morphology of the human ventromedial prefrontal cortex. AB - A previous report identified the location of comparable architectonic areas in the ventral frontal cortex of the human and macaque brains [S. Mackey & M. Petrides (2010) Eur. J. Neurosci., 32, 1940-1950]. The present article provides greater detail with regard to the definition of architectonic areas within the ventromedial part of the human ventral frontal cortex and describes their location: (i) in Montreal Neurological Institute proportional stereotactic space; and (ii) in relation to sulcal landmarks. Structural magnetic resonance scans of four brains were obtained before the preparation of the histological specimens, so that the architectonic parcellation could be reconstructed in its original three-dimensional volume. The areal density of individual cortical layers was sampled quantitatively in the ventromedial prefrontal cortex of eight brains (16 hemispheres). The agranular cortex along the ventral edge of the corpus callosum and posterior margin of the ventromedial surface is replaced by a graded series of increasingly granular and more complexly laminated areas that succeed one another in a posterior-to-anterior direction. In parallel, the width of the supragranular layers (i.e. layers II and III) increases as compared with the infragranular layers (i.e. layers V and VI) from posterior to anterior. A measure of how rapidly cortical features change at areal boundaries also showed that the rate of change in the granule and pyramidal cell densities of layers IV and V, respectively, was greater at the borders between posterior areas than between anterior areas. This article will facilitate the anatomical identification and comparison of experimental data involving the human vmPFC. PMID- 25123210 TI - Long-term systemic inflammation and cognitive impairment in a population-based cohort. AB - OBJECTIVES: Evidence suggests inflammation is associated with cognitive impairment, but previous epidemiological studies have reported conflicting results. DESIGN: Prospective population-based cohort. SETTING: Epidemiology of Hearing Loss Study participants. PARTICIPANTS: Individuals without cognitive impairment in 1998-2000 (N = 2,422; 1,947 with necessary data). MEASUREMENTS: Cognitive impairment (Mini-Mental State Examination score <24 or diagnosis of dementia) was ascertained in 1998-2000, 2003-2005, and 2009-2010. Serum C reactive protein (CRP) and interleukin-6 (IL-6) were measured in 1988-1990, 1998 2000, and 2009-2010; tumor necrosis factor-alpha was measured from 1998-2000. RESULTS: Participants with high CRP in 1988-1990 and 1998-2000 had lower risk of cognitive impairment than those with low CRP at both time points (hazard ratio (HR) = 0.46, 95% confidence interval (CI) = 0.26-0.80). Risk did not differ according to 10-year IL-6 profile or baseline inflammation category in the whole cohort. In sensitivity analyses restricted to statin nonusers, those with high IL 6 at both times had greater risk of cognitive impairment than those with low IL-6 at both times (HR = 3.35, 95% CI = 1.09-10.30). In secondary analyses, each doubling of IL-6 change over 20 years was associated with greater odds of cognitive impairment in 2009-2010 in the whole cohort (odds ratio (OR) = 1.40, 95% CI = 1.04-1.89), whereas a doubling of CRP change over 20 years was associated with cognitive impairment only in statin nonusers (OR = 1.32, 95% CI = 1.06-1.65). CONCLUSION: With data collected over 20 years, this study demonstrated greater likelihood of cognitive impairment in individuals with repeated high or increasing IL-6. The inconsistent CRP findings may reflect effects of statin medications, survival effects, or adverse effects associated with chronically low CRP. Further studies of long-term inflammation and cognitive impairment are needed. PMID- 25123214 TI - Contrasting electrogenerated chemiluminescence for a dissolved and surface attached carbazole thiophene cyanoacrylate dye. AB - The electrogenerated chemiluminescence (ECL) of a carbazole thiophene cyanoacrylate dye ((2-cyano-3-[5"'-(9-ethyl-9H-carbazol-3-yl)-3',3",3"',4-tetra-n hexyl-[2,2',5',2",5",2"']-quarter-thiophenyl-5yl]acrylate) = MK-2) has been investigated in solution, where the maximum ECL wavelength occurs at 640 nm, and in a thin film on an ITO surface, where the ECL is substantially red-shifted to 730 nm. The ECL intensity for the solution annihilation reaction is relatively weak, whereas a much higher ECL intensity is measured with oxalate as a co reactant. This result is attributed to the two Nernstian reversible oxidation waves of the thiophene moiety of MK-2, whereas the reduction is stabilized by the unblocked carbazole and cyanoacrylate groups. PMID- 25123212 TI - Baby steps: investigating the development of perceptual-motor couplings in infancy. AB - There are cells in our motor cortex that fire both when we perform and when we observe similar actions. It has been suggested that these perceptual-motor couplings in the brain develop through associative learning during correlated sensorimotor experience. Although studies with adult participants have provided support for this hypothesis, there is no direct evidence that associative learning also underlies the initial formation of perceptual-motor couplings in the developing brain. With the present study we addressed this question by manipulating infants' opportunities to associate the visual and motor representation of a novel action, and by investigating how this influenced their sensorimotor cortex activation when they observed this action performed by others. Pre-walking 7-9-month-old infants performed stepping movements on an infant treadmill while they either observed their own real-time leg movements (Contingent group) or the previously recorded leg movements of another infant (Non-contingent control group). Infants in a second control group did not perform any steps and only received visual experience with the stepping actions. Before and after the training period we measured infants' sensorimotor alpha suppression, as an index of sensorimotor cortex activation, while they watched videos of other infants' stepping actions. While we did not find greater sensorimotor alpha suppression following training in the Contingent group as a whole, we nevertheless found that the strength of the visuomotor contingency experienced during training predicted the amount of sensorimotor alpha suppression at post-test in this group. We did not find any effects of motor experience alone. These results suggest that the development of perceptual-motor couplings in the infant brain is likely to be supported by associative learning during correlated visuomotor experience. PMID- 25123215 TI - Compression force on the upper jaw during neonatal intubation: mannequin study. AB - AIM: Neonatal intubation is a technically challenging procedure, and pressure related injuries to surrounding structures have been reported. The primary objective of this study was to determine the pressure exerted on the upper jaw during tracheal intubation using a neonatal mannequin. METHOD: Multidisciplinary care providers working at a neonatal intensive care unit were requested to intubate a neonatal mannequin using the standard laryngoscope and 3.0-mm (internal diameter) endotracheal tube. Compression force exerted was measured by using pressure-sensitive film taped on the upper jaw before every intubation attempt. Pressure, area under pressure and time taken to intubate were compared between the different types of health-care professionals. RESULTS: Thirty care providers intubated the mannequin three times each. Pressure impressions were observed on the developer film after every intubation attempt (n = 90). The mean pressure exerted during intubation across all health-care providers was 568 kPa (SD 78). The mean area placed under pressure was 142 mm(2) (SD 45), and the mean time taken for intubation was 14.7 s (SD 4.3). There was no difference in pressure exerted on the upper jaw between frequent and less frequent intubators. It was found that pressure greater than 400 kPa was inadvertently applied on the upper jaw during neonatal intubation, far exceeding the 250 kPa shown to cause tissue injury in animal models. CONCLUSION: The upper jaw is exposed to a significant compression force during intubation. Although such exposure is brief, it has the potential to cause tissue injury. Contact of the laryngoscope blade with the upper jaw occurred in all intubation attempts with the currently used design of laryngoscope. PMID- 25123213 TI - Epidemiology and clinical characteristics of autoimmune hepatitis in the Netherlands. AB - BACKGROUND AND AIMS: Epidemiological data on autoimmune hepatitis (AIH) are scarce. In this study, we determined the clinical and epidemiological characteristics of AIH patients in the Netherlands (16.7 million inhabitants). METHODS: Clinical characteristics were collected from 1313 AIH patients (78% females) from 31 centers, including all eight academic centers in the Netherlands. Additional data on ethnicity, family history and symptoms were obtained by the use of a questionnaire. RESULTS: The prevalence of AIH was 18.3 (95% confidential interval [CI]: 17.3-19.4) per 100,000 with an annual incidence of 1.1 (95% CI: 0.5-2) in adults. An incidence peak was found in middle-aged women. At diagnosis, 56% of patients had fibrosis and 12% cirrhosis in liver biopsy. Overall, 1% of patients developed HCC and 3% of patients underwent liver transplantation. Overlap with primary biliary cirrhosis and primary sclerosing cholangitis was found in 9% and 6%, respectively. The clinical course did not differ between Caucasian and non-Caucasian patients. Other autoimmune diseases were found in 26% of patients. Half of the patients reported persistent AIH related symptoms despite treatment with a median treatment period of 8 years (range 1-44 years). Familial occurrence was reported in three cases. CONCLUSION: This is the largest epidemiological study of AIH in a geographically defined region and demonstrates that the prevalence of AIH in the Netherlands is uncommon. Although familial occurrence of AIH is extremely rare, our twin data may point towards a genetic predisposition. The high percentage of patients with cirrhosis or fibrosis at diagnosis urges the need of more awareness for AIH. PMID- 25123216 TI - Letter by Kirchoff-Torres and Labovitz regarding article, "Lifelong rupture risk of intracranial aneurysms depends on risk factors: a prospective Finnish cohort study". PMID- 25123218 TI - Response to letter regarding article, "Lifelong rupture risk of intracranial aneurysms depends on risk factors: a prospective Finnish cohort study". PMID- 25123217 TI - Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke. AB - BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is prevalent and there is a clinical need for biomarkers to identify individuals at higher risk for AF. Fixed throughout a life course and assayable early in life, genetic biomarkers may meet this need. Here, we investigate whether multiple single nucleotide polymorphisms together as an AF genetic risk score (AF-GRS) can improve prediction of one's risk for AF. METHODS: In 27 471 participants of the Malmo Diet and Cancer Study, a prospective, community-based cohort, we used Cox models that adjusted for established AF risk factors to assess the association of AF-GRS with incident AF and ischemic stroke. Median follow-up was 14.4 years for incident AF and 14.5 years for ischemic stroke. The AF-GRS comprised 12 single nucleotide polymorphisms that had been previously shown to be associated with AF at genome wide significance. RESULTS: During follow-up, 2160 participants experienced a first AF event and 1495 had a first ischemic stroke event. Participants in the top AF-GRS quintile were at increased risk for incident AF (hazard ratio, 2.00; 95% confidence interval, 1.73-2.31; P=2.7*10(-21)) and ischemic stroke (hazard ratio, 1.23; 95% confidence interval, 1.04-1.46; P=0.02) when compared with the bottom quintile. Addition of the AF-GRS to established AF risk factors modestly improved both discrimination and reclassification (P<0.0001 for both). CONCLUSIONS: An AF-GRS can identify 20% of individuals who are at ~2-fold increased risk for incident AF and at 23% increased risk for ischemic stroke. Targeting diagnostic or therapeutic interventions to this subset may prove clinically useful. PMID- 25123219 TI - Circuit class therapy and 7-day-week therapy increase physiotherapy time, but not patient activity: early results from the CIRCIT trial. AB - BACKGROUND AND PURPOSE: The optimum model of physiotherapy service delivery for maximizing active task practice during rehabilitation after stroke is unknown. The purpose of the study was to examine the relative effectiveness of 2 alternative models of physiotherapy service delivery against a usual care control with regard to increasing patient activity. METHODS: Substudy within a large 3 armed randomized controlled trial, which compared 3 different models of physiotherapy service delivery, was provided for 4 weeks during subacute, inpatient rehabilitation (n=283). The duration of all physiotherapy sessions was recorded. In addition, 32 participants were observed at 10-minute intervals for 1 weekday and 1 weekend day between 8:00 am and 4:30 pm. At each observation, we recorded physical activity, location, and people present. RESULTS: Participants receiving 7-day-week and circuit class therapy received an additional 3 hours and 22 hours of physiotherapy time, respectively, when compared with usual care. Participants were standing or walking for a median of 8.2% of observations. On weekdays, circuit class therapy participants spent more time in therapy-related activity (10.2% of observations) when compared with usual care participants (6.1% of observations). On weekends, 7-day therapy participants spent more time in therapy-related activity (4.2% of observations) when compared with both usual care and circuit class therapy participants (0% of observations for both groups). Activity levels outside of therapy sessions did not differ between groups. CONCLUSIONS: A greater dosage of physiotherapy time did not translate into meaningful increases in physical activity across the day. CLINICAL TRIAL REGISTRATION URL: http://www.anzctr.org.au/. Unique identifier: ACTRN12610000096055. PMID- 25123220 TI - Combined effects of socioeconomic position, smoking, and hypertension on risk of ischemic and hemorrhagic stroke. AB - BACKGROUND AND PURPOSE: Combined effects of socioeconomic position and well established risk factors on stroke incidence have not been formally investigated. METHODS: In a pooled cohort study of 68 643 men and women aged 30 to 70 years in Denmark, we examined the combined effect and interaction between socioeconomic position (ie, education), smoking, and hypertension on ischemic and hemorrhagic stroke incidence by the use of the additive hazards model. RESULTS: During 14 years of follow-up, 3613 ischemic strokes and 776 hemorrhagic strokes were observed. Current smoking and hypertension were more prevalent among those with low education. Low versus high education was associated with greater ischemic, but not hemorrhagic, stroke incidence. The combined effect of low education and current smoking was more than expected by the sum of their separate effects on ischemic stroke incidence, particularly among men: 134 (95% confidence interval, 49-219) extra cases per 100 000 person-years because of interaction, adjusted for age, cohort study, and birth cohort. There was no clear evidence of interaction between low education and hypertension. The combined effect of current smoking and hypertension was more than expected by the sum of their separate effects on ischemic and hemorrhagic stroke incidence. This effect was most pronounced for ischemic stroke among women: 178 (95% confidence interval, 103-253) extra cases per 100 000 person-years because of interaction, adjusted for age, cohort study, and birth cohort. CONCLUSIONS: Reducing smoking in those with low socioeconomic position and in those with hypertension could potentially reduce social inequality stroke incidence. PMID- 25123221 TI - Better health, less spending: delivery innovation for ischemic cerebrovascular disease. PMID- 25123223 TI - Statin therapy for venous ulcers. PMID- 25123222 TI - Low levels of low-density lipoprotein-C associated with proprotein convertase subtilisin kexin 9 inhibition do not increase the risk of hemorrhagic transformation. AB - BACKGROUND AND PURPOSE: Low levels of low-density lipoprotein-cholesterol (LDL-C) are suspected to be associated with a risk of hemorrhagic transformation after ischemic stroke. We assessed the risk of hemorrhagic transformation after cerebral ischemia/reperfusion in mice with low levels of LDL-C resulting from proprotein convertase subtilisin kexin 9 (PCSK9) deficiency. METHODS: PCSK9-/- and PCSK9+/+ mice were fed with a high-fat/high-cholesterol (21%/0.15%) diet for 1 month. Plasma lipids were measured using colorimetric assays. PCSK9-/- and PCSK9+/+ mice (n=15 per group) were subjected to a 4-hour intraluminal occlusion of the middle cerebral artery followed by 20 hours of reperfusion. Spontaneous hemorrhagic transformation was assessed by quantification of hemoglobin in ischemic tissue. In vitro, a cell model of blood-brain barrier was used to test endothelial barrier integrity in response to decreasing concentrations of LDL-C from 1 to 0.25g/L in ischemia/reperfusion conditions. RESULTS: PCSK9-/- mice had lower LDL-C, high-density lipoprotein-cholesterol, and total cholesterol levels than PCSK9+/+ mice before and after 1 month on the high-fat/high-cholesterol diet. Hemoglobin concentration in ischemic cerebral tissue was not different between PCSK9-/- and PCSK9+/+ mice (31.5 [18.9-60.1] and 32.8 [14.7-69.9] ng/mg protein, respectively; P=0.81). Infarct volume was also similar in both groups (P=0.66). Incubation of human cerebral endothelial cells with decreasing concentrations of LDL-C under ischemia/reperfusion conditions did not alter blood brain barrier permeability. CONCLUSIONS: Low levels of LDL-C did not increase the risk of hemorrhagic transformation after cerebral ischemia/reperfusion in mice. Our observations suggest that PCSK9 inhibition, leading to LDL-C lowering, should not increase hemorrhagic complications after acute ischemic stroke. PMID- 25123224 TI - Pneumocyte injury and ubiquitin-positive pneumocytes in interstitial lung diseases. AB - Pneumocyte injury is a characteristic of pulmonary interstitial pneumonias (IPs). Histological markers of pneumocyte injury and inflammation include pneumocyte necrosis, erosion, hyaline membrane and fibrin exudation with subsequent intraluminal granulation tissue formation. We found that intracytoplasmic inclusions in pneumocytes are ubiquitin-positive (Ub(+) ) and that the number of Ub(+) pneumocytes shows positive correlation with the extent of diffuse alveolar damage (DAD). To determine the role of Ub(+) pneumocytes and inclusions in IPs, we studied their relationship with pathological and clinical features of DAD, usual interstitial pneumonia (UIP) and organizing pneumonia (OP), including airspace enlargement with fibrosis (AEF). We analysed Ub(+) pneumocytes, inclusions, erosions and intraluminal granulation tissue in relation to pneumocyte injury. The numbers of immunohistochemically identified Ub(+) inclusions in each IP were higher than the number of inclusions detected by light microscopy. The inclusions detected by Ub(+) immunostaining were identical to the inclusions observed by light microscopy. UIP and DAD had many Ub(+) inclusions, while OP and AEF had fewer Ub(+) inclusions. These results suggest that the extent of Ub(+) inclusions reflects the severity of pneumocyte injury among IPs. Thus, Ub(+) inclusions are a histological marker of pneumocyte injury that may be helpful in determining the severity and prognosis of IPs. PMID- 25123226 TI - Assessment of ocular pain following ranibizumab intravitreal injection. PMID- 25123225 TI - Synthetic biology approaches to improve biocatalyst identification in metagenomic library screening. AB - There is a growing demand for enzymes with improved catalytic performance or tolerance to process-specific parameters, and biotechnology plays a crucial role in the development of biocatalysts for use in industry, agriculture, medicine and energy generation. Metagenomics takes advantage of the wealth of genetic and biochemical diversity present in the genomes of microorganisms found in environmental samples, and provides a set of new technologies directed towards screening for new catalytic activities from environmental samples with potential biotechnology applications. However, biased and low level of expression of heterologous proteins in Escherichia coli together with the use of non-optimal cloning vectors for the construction of metagenomic libraries generally results in an extremely low success rate for enzyme identification. The bottleneck arising from inefficient screening of enzymatic activities has been addressed from several perspectives; however, the limitations related to biased expression in heterologous hosts cannot be overcome by using a single approach, but rather requires the synergetic implementation of multiple methodologies. Here, we review some of the principal constraints regarding the discovery of new enzymes in metagenomic libraries and discuss how these might be resolved by using synthetic biology methods. PMID- 25123227 TI - Genetic alterations of chromosome 8 genes in oral cancer. AB - The clinical relevance of DNA copy number alterations in chromosome 8 were investigated in oral cancers. The copy numbers of 30 selected genes in 33 OSCC patients were detected using the multiplex ligation-dependent probe amplification (MLPA) technique. Amplifications of the EIF3E gene were found in 27.3% of the patients, MYC in 18.2%, RECQL4 in 15.2% and MYBL1 in 12.1% of patients. The most frequent gene losses found were the GATA4 gene (24.2%), FGFR1 gene (24.2%), MSRA (21.2) and CSGALNACT1 (12.1%). The co-amplification of EIF3E and RECQL4 was found in 9% of patients and showed significant association with alcohol drinkers. There was a significant association between the amplification of EIF3E gene with non betel quid chewers and the negative lymph node status. EIF3E amplifications did not show prognostic significance on survival. Our results suggest that EIF3E may have a role in the carcinogenesis of OSCC in non-betel quid chewers. PMID- 25123229 TI - Avoiding perceived past resource use of potential competitors affects niche dynamics in a bird community. AB - BACKGROUND: Social information use is usually considered to lead to ecological convergence among involved con- or heterospecific individuals. However, recent results demonstrate that observers can also actively avoid behaving as those individuals being observed, leading to ecological divergence. This phenomenon has been little explored so far, yet it can have significant impact on resource use, realized niches and species co-existence. In particular, the time-scale and the ecological context over which such shifts can occur are unknown. We examined with a long-term (four years) field experiment whether experimentally manipulated, species-specific, nest-site feature preferences (symbols on nest boxes) are transmitted across breeding seasons and affect future nest-site preferences in a guild of three cavity-nesting birds. RESULTS: Of the examined species, resident great tits (Parus major) preferred the symbol that had been associated with unoccupied nest boxes in the previous year, i.e., their preference shifted towards niche space previously unused by putative competitors and conspecifics. CONCLUSIONS: Our results show that animals can remember the earlier resource use of conspecifics and other guild members and adjust own decisions accordingly one year after. Our experiment cannot reveal the ultimate mechanism(s) behind the observed behaviour but avoiding costs of intra- or interspecific competition or ectoparasite load in old nests are plausible reasons. Our findings imply that interspecific social information use can affect resource sharing and realized niches in ecological time-scale through active avoidance of observed decisions and behavior of potentially competing species. PMID- 25123228 TI - Cyclic phosphatidic acid relieves osteoarthritis symptoms. AB - BACKGROUND: Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. Natural cPA and its chemically stabilized cPA derivative, 2-carba-cPA (2ccPA), inhibit chronic and acute inflammation, and 2ccPA attenuates neuropathic pain. Osteoarthritis (OA) is a degenerative disease frequently associated with symptoms such as inflammation and joint pain. Because 2ccPA has obvious antinociceptive activity, we hypothesized that 2ccPA might relieve the pain caused by OA. We aimed to characterize the effects of 2ccPA on the pathogenesis of OA induced by total meniscectomy in the rabbit knee joint. RESULTS: Intra-articular injection of 2ccPA (twice a week for 42 days) significantly reduced pain and articular swelling. Histopathology showed that 2ccPA suppressed cartilage degeneration in OA. We also examined the effects of 2ccPA on the inflammatory and catabolic responses of human OA synoviocytes and chondrosarcoma SW1353 cells in vitro. 2ccPA stimulated synthesis of hyaluronic acid and suppressed production of the metalloproteinases MMP-1, -3, and -13. However, it had no effect on the production of interleukin (IL)-6, an inflammatory cytokine. The suppressive effect of 2ccPA on MMP-1 and -3 production in synoviocytes and on MMP-13 production in SW1353 cells was not mediated by the lysophosphatidic acid receptor, LPA1 receptor (LPA1R). CONCLUSIONS: Our results suggest that 2ccPA significantly reduces the pain response to OA by inducing hyaluronic acid production and suppressing MMP-1, -3, and -13 production in synoviocytes and chondrocytes. PMID- 25123230 TI - The (cost) effectiveness of an online intervention for pregnant women with affective symptoms: protocol of a randomised controlled trial. AB - BACKGROUND: Women in pregnancy and postpartum have an increased vulnerability to develop an affective disorder. Affective disorders in pregnancy are associated with an increased risk of prematurity, dysmaturity (foetal weight below the 10th percentile as determined by ultrasound) and the development of postpartum depressive disorder. Untreated affective disorders and their complications may also result in considerable costs. Recent meta-analyses showed that interventions during pregnancy are less effective than postpartum interventions probably because of high attrition due to the barriers pregnant women experience with attending sessions outside their homes. An internet-based self-help intervention may overcome these barriers as it can be followed at home, and also in one's own time. Such internet interventions showed to be effective for decreasing affective symptoms in general.This randomised clinical trial examines whether an internet based self-help intervention is effective in the reduction of affective symptoms in pregnancy and postpartum and results in an improvement of the perinatal outcome. We will also determine the cost-effectiveness of the intervention. METHODS/DESIGN: We will investigate the effectiveness of a 6 week internet-based self-help problem solving treatment (PST) for affective symptoms in pregnancy. We aim to include 286 women with mild to severe affective symptoms who will be randomly assigned to the internet-based intervention or a waiting list control group. Primary outcome measures are affective symptoms and the perinatal outcome. Secondary outcome measures are quality of life, and economic costs. All assessments are based on self-report and will take place at baseline (T0), 10 weeks later (after completion of the intervention (T1), 4 weeks before the expected day of birth (T2), and 6 weeks after delivery (T3). The control group will be measured at the same moments in time. Analysis will be based on the intention-to-treat principle. DISCUSSION: If shown (cost) effective, internet based PST will offer new possibilities to treat pregnant women for affective symptoms, to improve their perinatal outcome and to prevent the development of postpartum depressive disorders. TRIAL REGISTRATION: Nederlands Trial Register: NTR4321. PMID- 25123232 TI - What is the association of heme aggregates with the peritrophic matrix of adult female mosquitoes? AB - The aim of this Letter is to call attention to the presence of iron-containing or heme aggregates seen within or near the peritrophic matrix (PM) in published Anopheles gambiae and Aedes aegypti midgut micrographs. The micrographs shown here suggest that the PM of An. gambiae adult female is not a homogenous layer and instead may have a peritrophin layer surrounded by heme aggregates that are possibly associated to other molecules involved in their formation. In depth studies addressing PM structure in different mosquito species are needed, as these will be important to continue clarifying the roles of the PM. PMID- 25123233 TI - Cost-effectiveness analysis of endoscopic sphenopalatine artery ligation vs arterial embolization for intractable epistaxis. AB - IMPORTANCE: Intractable epistaxis is a common otolaryngology emergency. Transnasal endoscopic sphenopalatine artery ligation (TESPAL) and endovascular arterial embolization both provide excellent success rates, and therefore the decision to choose one over the other can be challenging. OBJECTIVE: To aid in decision making by evaluating the cost-effectiveness of TESPAL vs endovascular arterial embolization for intractable epistaxis. DESIGN, SETTING, AND PARTICIPANTS: Economic evaluation using a decision tree model with a 14-day time horizon for emergency department consultations for patients with intractable epistaxis defined as persistent bleeding despite bilateral anterior nasal packing. The economic perspective was the health care third-party payer. Effectiveness and probability data were obtained from the published medical literature. Costs were obtained from the published literature, the Centers for Medicare & Medicaid Services database, and the Healthcare Cost and Utilization Project database. Multiple sensitivity analyses were performed, including a probabilistic sensitivity analysis. Comparative treatment groups were (1) TESPAL and (2) embolization. INTERVENTIONS: TESPAL and endovascular arterial embolization. MAIN OUTCOME AND MEASURES: The primary outcome was the incremental cost-effectiveness ratio (ICER) for successful control of epistaxis. RESULTS: The reference case demonstrated that the embolization strategy was more effective but more costly compared with the TESPAL strategy: $22,324.70 per 0.70 effectiveness compared with $12,484.14 per 0.68 of effectiveness, respectively. The embolization vs TESPAL ICER was $492,028, which is higher than any willingness to pay (WTP), suggesting that TESPAL is the cost-effective decision. The sensitivity analysis demonstrated a 77.6% and 73.7% certainty that the TESPAL strategy is cost-effective at WTP thresholds of $10,000 and $50,000, respectively. CONCLUSIONS AND RELEVANCE: Results from this economic evaluation suggest that when both TESPAL and arterial embolization are viable options (based on patient and institutional factors), TESPAL is the more cost-effective treatment strategy for patients with intractable epistaxis. PMID- 25123231 TI - Modeling the dependence of respiration and photosynthesis upon light, acetate, carbon dioxide, nitrate and ammonium in Chlamydomonas reinhardtii using design of experiments and multiple regression. AB - BACKGROUND: In photosynthetic organisms, the influence of light, carbon and inorganic nitrogen sources on the cellular bioenergetics has extensively been studied independently, but little information is available on the cumulative effects of these factors. Here, sequential statistical analyses based on design of experiments (DOE) coupled to standard least squares multiple regression have been undertaken to model the dependence of respiratory and photosynthetic responses (assessed by oxymetric and chlorophyll fluorescence measurements) upon the concomitant modulation of light intensity as well as acetate, CO2, nitrate and ammonium concentrations in the culture medium of Chlamydomonas reinhardtii. The main goals of these analyses were to explain response variability (i.e. bioenergetic plasticity) and to characterize quantitatively the influence of the major explanatory factor(s). RESULTS: For each response, 2 successive rounds of multiple regression coupled to one-way ANOVA F-tests have been undertaken to select the major explanatory factor(s) (1st-round) and mathematically simulate their influence (2nd-round). These analyses reveal that a maximal number of 3 environmental factors over 5 is sufficient to explain most of the response variability, and interestingly highlight quadratic effects and second-order interactions in some cases. In parallel, the predictive ability of the 2nd-round models has also been investigated by k-fold cross-validation and experimental validation tests on new random combinations of factors. These validation procedures tend to indicate that the 2nd-round models can also be used to predict the responses with an inherent deviation quantified by the analytical error of the models. CONCLUSIONS: Altogether, the results of the 2 rounds of modeling provide an overview of the bioenergetic adaptations of C. reinhardtii to changing environmental conditions and point out promising tracks for future in-depth investigations of the molecular mechanisms underlying the present observations. PMID- 25123234 TI - A pilot prospective study to evaluate whether the bladder morphology in cystography and/or urodynamic may help predict the response to botulinum toxin a injection in neurogenic bladder refractory to anticholinergics. AB - BACKGROUND: We have observed different clinical responses to botulinum toxin A (BTX-A) in patients who had similar urodynamic parameters before the procedure. Furthermore, some bladders evaluated by cystography and cystoscopy during the procedure had different characteristics that could influence the outcome of the treatment. The aim of this study was to assess whether cystography and urodynamic parameters could help predict which patients with neurogenic detrusor overactivity (NDO) refractory to anticholinergics respond better to treatment with injection of BTX-A. METHODS: In total, 34 patients with spinal cord injury were prospectively evaluated. All patients emptied their bladder by clean intermittent catheterization (CIC) and had incontinence and NDO, despite using 40 mg or more of intravesical oxybutynin and undergoing detrusor injection of BTX-A (300 IU). Pretreatment evaluation included urodynamic, and cystography. Follow-up consisted of urodynamic and ambulatory visits four months after treatment. The cystography parameters used were bladder shape, capacity and presence of diverticula. Urodynamic parameters used for assessment were maximum cystometric capacity (MCC), maximum detrusor pressure (MDP), compliance and reflex volume (RV). RESULTS: After injection of BTX-A, 70% of the patients had success, with 4 months or more of continence. Before the treatment, there were significant differences in most urodynamic parameters between those who responded successfully compared to those who did not. Patients who responded successfully had greater MCC (p = 0.019), higher RV (p = 0.041), and greater compliance (p = 0.043). There was no significant difference in the MDP (0.691). The cystography parameters were not significantly different between these groups bladder shape (p = 0.271), capacity (p > 0.720) and presence of diverticula (p > 0.999). Statistical analyses were performed using SPSS (version 20.0) and included Student's t-test for two paired samples and Fisher's exact test, with a significance threshold of 0.05. CONCLUSIONS: This study suggests that the cystography parameters evaluated cannot be used to help predict the response to injection of BTX-A in the treatment of refractory NDO. However, the urodynamic parameters were significantly different in patients who responded to the treatment, with the exception of the MDP. PMID- 25123236 TI - Similar differentiation patterns between PBP expression levels and pheromone component ratios in two populations of Sesamia nonagrioides. AB - Pheromone-binding proteins (PBPs) are thought to contribute to the specificity of the pheromone detection system through an initial selective binding with pheromone molecules. Here, we report different expression levels of PBP transcripts in the antennae of two populations of the stemborer Sesamia nonagrioides (Lepidoptera: Noctuidae), one collected in Europe and one in sub Saharan Africa. The three PBP transcripts previously identified in this species were found to be expressed in both male and female antennae. Whereas PBP3 did not show any differential expression, PBP1 and PBP2 appeared to be expressed differently according to the population origin and sex. Simultaneously, we measured and compared the ratio of the three components of the S. nonagrioides pheromone blend (Z11-16:Ac; Z11-16:OH; Z11-16:Ald) in females of the two populations. The ratio of Z11-16:OH and Z11-16:Ald varied significantly according to the population origin of this species. Cluster analyses revealed similar differentiation patterns between PBP1 and PBP2 expression levels and the ratios of Z11-16:OH and Z11-16:Ald. Different female sexual signals may thus correspond to different male reception systems, which are adjusted by the PBP expression levels, thereby ensuring optimal communication within populations. PMID- 25123235 TI - Topically applied ZnO nanoparticles suppress allergen induced skin inflammation but induce vigorous IgE production in the atopic dermatitis mouse model. AB - BACKGROUND: Metal oxide nanoparticles such as ZnO are used in sunscreens as they improve their optical properties against the UV-light that causes dermal damage and skin cancer. However, the hazardous properties of the particles used as UV filters in the sunscreens and applied to the skin have remained uncharacterized. METHODS: Here we investigated whether different sized ZnO particles would be able to penetrate injured skin and injured allergic skin in the mouse atopic dermatitis model after repeated topical application of ZnO particles. Nano-sized ZnO (nZnO) and bulk-sized ZnO (bZnO) were applied to mechanically damaged mouse skin with or without allergen/superantigen sensitization. Allergen/superantigen sensitization evokes local inflammation and allergy in the skin and is used as a disease model of atopic dermatitis (AD). RESULTS: Our results demonstrate that only nZnO is able to reach into the deep layers of the allergic skin whereas bZnO stays in the upper layers of both damaged and allergic skin. In addition, both types of particles diminish the local skin inflammation induced in the mouse model of AD; however, nZnO has a higher potential to suppress the local effects. In addition, especially nZnO induces systemic production of IgE antibodies, evidence of allergy promoting adjuvant properties for topically applied nZnO. CONCLUSIONS: These results provide new hazard characterization data about the metal oxide nanoparticles commonly used in cosmetic products and provide new insights into the dermal exposure and hazard assessment of these materials in injured skin. PMID- 25123237 TI - Prevalence and drug resistance of mycobacteria in Turkish cystic fibrosis patients. AB - BACKGROUND: Isolation of mycobacteria in cystic fibrosis (CF) patients is increasingly being reported. Because of having long term antimicrobial treatment, CF patients are at risk of pulmonary infection with especially resistant nontuberculous mycobacteria (NTM) strains. The aim of the present study is to determine the prevalence of mycobacterium spp. and antimicrobial susceptibility in Turkish CF patients. METHODS: During a 5.5 year study period, 376 sputa from 130 CF patients were analyzed. Antimycobacterial susceptibility testing was performed by the Bactec 460 TB System and the E test method. RESULTS: Totaly 28 (7.44%) Mycobacterium spp. were isolated from eight (6.15%) CF patients. Five isolates (17.9%) were identified as Mycobacterium tuberculosis complex (MTBC), 14 (50%) as Mycobacterium abscessus and nine (32.1%) as Mycobacterium lentiflavum. All MTBC isolates were found to be susceptible to streptomycin, isoniazid, rifampicin, and ethambutol. Resistance to some antibiotics was detected in some NTM strains. These are the first data about the prevalence of mycobacteria in CF patients from Turkey. CONCLUSIONS: In pediatric CF patients, specific mycobacterial analysis of sputum specimens and susceptibility testing should be performed for allowing early detection, identification and the possibility of eradication of these bacteria. PMID- 25123238 TI - Intravenous iron sucrose: an alternative for oral iron in pregnancy with iron deficiency anemia. PMID- 25123239 TI - The John Charnley Award: Highly crosslinked polyethylene in total hip arthroplasty decreases long-term wear: a double-blind randomized trial. AB - BACKGROUND: The use of highly crosslinked polyethylene (HXLPE) is now commonplace for total hip arthroplasty. Hip simulator studies and short-term in vivo measurements suggest that the wear rate of some types of HXLPE is significantly less than conventional ultrahigh-molecular-weight polyethylene (UHMWPE). However, there are few long-term data to support its use. QUESTIONS/PURPOSES: The aim of this study was to measure the long-term steady-state wear of HXLPE compared with UHMWPE liners in a prospective, double-blind, randomized controlled trial using radiostereometric analysis. METHODS: Fifty-four patients were randomized to receive hip arthroplasties with either UHMWPE liners or HXLPE liners. Complete followup was available on 39 of these patients (72%). All patients received the same cemented stem and an uncemented acetabular component. Three-dimensional penetration of the head into the socket was determined at 10 years using a radiostereometric analysis system, which has an in vivo accuracy of <0.1 mm. Oxford Hip Scores were compared between the groups. RESULTS: At 10 years there was significantly less wear of HXLPE (0.003 mm/year; 95% confidence interval [CI], +/-0.010; SD 0.023; range, -0.057 to 0.074) compared with UHMWPE (0.030 mm/year; 95% CI, +/-0.012; p<0.001; SD 0.0.27; range, -0.001 to 0.164). The volumetric penetration from 1 to 10 years for the UHMWPE group was 98 mm3 (95% CI, +/-46 mm3; SD 102 mm3; range, -4 to 430 mm3) compared with 14 mm3 (95% CI, +/ 40 mm3; SD 91 mm3; range, -189 to 242 mm3) for the HXLPE group (p=0.01). CONCLUSIONS: This study demonstrates that HXLPE has little detectable steady state in vivo wear. This may result in fewer reoperations from loosening; however, careful clinical followup into the second decade still needs to be performed. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 25123240 TI - Does HIV infection increase the risk of perioperative complications after THA? A nationwide database study. AB - BACKGROUND: Recent studies have shown successful midterm outcomes after total hip arthroplasty (THA) in patients with human immunodeficiency virus (HIV). However, little data exist on the epidemiology, risk of perioperative complications, and length of stay in patients with HIV receiving THA. QUESTIONS/PURPOSES: The purposes of this study were to assess (1) the demographic trends of patients with HIV who underwent primary THA; (2) the differences in the risk of major and minor perioperative complications among patients with and without HIV; and (3) the differences in mean length of hospital stay among patients with and without HIV. METHODS: The Nationwide Inpatient Sample was used to compare patients with and without HIV who were admitted for THA between 1998 and 2010 in the United States. We extracted data on each admission's age, sex, race, insurance, and comorbidities. The study population consisted of 2,656,696 patients without HIV and 9275 patients with HIV. RESULTS: Patients with HIV were more likely to be younger, be male, not pay with Medicare, and be of a nonwhite race. After controlling for confounding variables, patients with HIV were more likely to have major complications (2.9% [266 of 9275] versus 2.7% [71,952 of 2,656,696]; odds ratio [OR], 1.47; 95% confidence interval [CI], 1.08-2.00; p=0.014) and minor complications (5.2% [483 of 9275] versus 4.8% [127,940 of 2,656,696]; OR, 1.61; 95% CI, 1.29-2.02; p<0.001) compared with patients who did not have HIV. Patients undergoing THA who had HIV also had an increased length of hospital stay compared with patients without HIV (4.31 versus 3.83 days, p<0.001). CONCLUSIONS: Given these findings, we believe orthopaedic surgeons should be aware of the potential for longer and more complicated hospital stays after THA among patients with HIV. However, the modest increase in risk of adverse outcomes does not cause us to recommend against THA for patients with HIV who otherwise meet reasonable surgical indications. Future studies should explore the relationships between markers of HIV severity and risk of adverse outcomes after THA during the hospital stay and followup. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 25123241 TI - Continued good results with modular trabecular metal augments for acetabular defects in hip arthroplasty at 7 to 11 years. AB - BACKGROUND: Reconstruction of large acetabular defects remains a substantial challenge in hip arthroplasty. There remains a paucity of data on the long-term results of acetabular trabecular metal augments. QUESTIONS/PURPOSES: The purpose of this study was to assess the survivorship, clinical outcomes, restoration of center of rotation of the hip, and radiological signs of component fixation of trabecular metal augments in the context of reconstruction of acetabular defects. METHODS: Between 2002 and 2005, we performed 56 revision (n=53) and primary (n=3) THAs using trabecular metal augments in combination with a trabecular metal acetabular component. Of the 56 patients, 16 (29%) died during followup. Of the 40 surviving patients, 37 (93%) had complete radiological followup, 23 (58%) had complete outcome questionnaire followup, and 17 (42%) provided partial questionnaire responses in the clinic or over the telephone. Median followup was 110 months (range, 88-128 months). During that period, we used these implants when preoperative templating indicated that an augment would be required to achieve acetabular implant stability with restoration of the hip center of rotation. We also chose during surgery to use an augment when we could not achieve a stable acetabular trial component without one. The combination of trabecular metal augments and trabecular metal shells was used in 18% (53 of 292) of our acetabular revisions during that time. Survivorship, functional outcome (WOMAC and Oxford hip score), health status (SF-12), and osseointegration according to the criteria of Moore and presence of radiolucencies were determined. RESULTS: Survivorship of the augments at 10 years was 92% (95% confidence interval, 81%-97%). Four patients underwent cup revision, one for infection and three for loosening. The mean WOMAC global score was 79 (SD 17), the mean Oxford hip score 76 (SD 18), the mean physical component SF-12 score was 39 (SD 11), and the mean mental component SF-12 score was 52 (SD 9). The center of rotation was corrected from more than 35 mm above the inter-teardrop line in 48 of 56 patients preoperatively to only five of 46 postoperatively. One patient had radiographic findings suggestive of loosening, but this patient was asymptomatic. CONCLUSIONS: The results of the acetabular trabecular metal augments continue to be encouraging in the medium to long term with low rates of revision or loosening in this complex group of patients. We continue to recommend the use of these augments in the reconstruction of complex acetabular defects. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 25123242 TI - CORR Insights(r): minorities are less likely to receive autologous blood transfusion for major elective orthopaedic surgery. PMID- 25123243 TI - Do corresponding authors take responsibility for their work? A covert survey. AB - BACKGROUND: Publication of a manuscript does not end an author's responsibilities. Reasons to contact an author after publication include clarification, access to raw data, and collaboration. However, legitimate questions have been raised regarding whether these responsibilities generally are being met by corresponding authors of biomedical publications. QUESTIONS/PURPOSES: This study aims to establish (1) what proportion of corresponding authors accept the responsibility of correspondence; (2) identify characteristics of responders; and (3) assess email address decay with time. We hypothesize that the response rate is unrelated to journal impact factor. METHODS: We contacted 450 corresponding authors throughout various fields of biomedical research regarding the availability of additional data from their study, under the pretense of needing these data for a related review article. Authors were randomly selected from 45 journals whose impact factors ranged from 52 to 0; the source articles were published between May 2003 and May 2013. The proportion of corresponding authors who replied, along with author characteristics were recorded, as was the proportion of emails that were returned for inactive addresses; 446 authors were available for final analysis. RESULTS: Fifty-three percent (190/357) of the authors with working email addresses responded to our request. Clinical researchers were more likely to reply than basic/translational scientists (51% [114/225] versus 34% [76/221]; p<0.001). Impact factor and other author characteristics did not differ. Logistic regression analysis showed that the odds of replying decreased by 15% per year (odds ratio [OR], 0.85; 95% CI, 0.79-0.91; p<0.001), and showed a positive relationship between clinical research and response (OR, 2.0; 95% CI, 1.3-2.9; p=0.001). In 2013 all email addresses (45/45) were reachable, but within 10 years, 49% (21/43) had become invalid. CONCLUSIONS: Our results suggest that contacting corresponding authors is problematic throughout the field of biomedical research. Defining the responsibilities of corresponding authors by journals more explicitly-particularly after publication of their manuscript-may increase the response rate on data requests. Possible other ways to improve communication after research publication are: (1) listing more than one email address per corresponding author, eg, an institutional and personal address; (2) specifying all authors' email addresses; (3) when an author leaves an institution, send an automated reply offering alternative ways to get in touch; and (4) linking published manuscripts to research platforms. PMID- 25123244 TI - Cochrane in CORR(r): surgery for rotator cuff disease (review). PMID- 25123245 TI - Thigh pain in an 18-year-old man. PMID- 25123246 TI - Editorial comment: 2013Musculoskeletal Infection Society meeting. PMID- 25123247 TI - CORR Insights(r): does advanced cryotherapy reduce pain and narcotic consumption after knee arthroplasty? PMID- 25123249 TI - A significant inhibitory effect on advanced glycation end product formation by catechin as the major metabolite of lotus seedpod oligomeric procyanidins. AB - Several lines of evidence suggested that B-type procyanidin oligomers from lotus seedpod (LSOPC) may effectively modulate the formation of advanced glycation end products (AGEs). In vivo, LSOPC is metabolized by intestinal flora to become various kinds of phenolic compounds that possess potent antioxidant activities. However, few reports of the absorption and metabolism of LSOPC have been revealed. In the present study, rats were orally administered with LSOPC at a dose of 300 mg/kg body weight. The metabolites of LSOPC in urine were elucidated by HPLC-MS/MS analysis 24 h post-administration. Eight major metabolites were significantly increased by the administration of 300 mg/kg of LSOPC (p < 0.01). The anti-glycative activity of LSOPC and its metabolites were investigated. The results showed that LSOPC and catechin had greater anti-glycative activities than other metabolites, which were positively correlated to their carbonyl scavenging activities and antioxidant capacities. PMID- 25123248 TI - Vitamin E supplementation in chemical colorectal carcinogenesis: a two-edged knife. AB - This work investigated the effects of Vitamin E (VE) on aberrant crypt foci (ACF) incidence, oxidative stress parameters (serum and hepatic VE concentration, and homocysteine, glutathione (GSH), and malondialdehyde (MDA) levels), and expression of both cyclooxygenase-2 (COX2) and proliferating cellular nuclear antigen (PCNA) in experimental colorectal carcinogenesis. Male Wistar rats received subcutaneous injections of 1,2-dimethylhydrazine (DMH) twice a week, for two weeks (40 mg/kg), except for the Control group. Animals were separated into groups that received different amounts of VE in the diet: 0 IU (0*), 75 IU (recommended daily intake, RDI), 225 IU (3* RDI), or 1500 IU (20* RDI), during (dDMH) or after (aDMH) administration of carcinogen. The 0*dDMH and 3*dDMH groups showed decreased serum VE levels. Hepatic VE concentration was higher in 3*aDMH as compared with the other groups. All the groups, except the Control and the 0*aDMH groups, had reduced GSH levels. The 0*dDMH, 0*aDMH, and 20*aDMH groups exhibited increased MDA levels. The aDMH groups had higher ACF incidence and PCNA expression. The 0*aDMH group presented higher ACF rate, followed by 20*aDMH. Moreover, the 3*aDMH group displayed reduced ACF incidence and COX2 expression. Multivariate analysis revealed that GSH modulated homocysteine levels and COX2. These results suggested that 1500 IU of VE is hazardous, whereas 225 IU of VE has beneficial effects on chemical colorectal carcinogenesis. PMID- 25123251 TI - Etiopathogenesis of acquired cholesteatoma: prominent theories and recent advances in biomolecular research. AB - OBJECTIVE: To review recent biomolecular advances in etiopathogenesis of acquired cholesteatoma. DATA SOURCES: MEDLINE via OVID (to March 2014) and PubMed (to March 2014). REVIEW METHODS: All articles referring to etiopathogenesis of acquired cholesteatoma were identified in the above databases, from which 89 articles were included in this review. RESULTS: The mechanisms underlying the etiopathogenesis of acquired cholesteatoma remain a subject of competing hypotheses. Four theories dominate the debate, including theories of invagination, immigration, squamous metaplasia, and basal cell hyperplasia. However, no single theory has been able to explain the clinical characteristics of all cholesteatoma types: uncoordinated hyperproliferation, invasion, migration, altered differentiation, aggressiveness, and recidivism. Modern technologies have prompted a number of researchers to seek explanations at the molecular level. First, cholesteatomas could be considered an example of uncontrolled cell growth, capable of altering the balance toward cellular hyperproliferation and enhancing the capacity for invasion and osteolysis. Second, the dysregulation of cell growth control involves internal genomic or epigenetic alterations and external stimuli, which induce excessive host immune response to inflammatory and infectious processes. This comprises several complex and dynamic pathophysiologic changes that involve extracellular and intracellular signal transduction cascades. CONCLUSIONS: This article summarizes the existing theories and provides conceptual insights into the etiopathogenesis of acquired cholesteatoma, with the aim of stimulating continued efforts to develop a nonsurgical means of treating the disorder. PMID- 25123252 TI - In vitro performance and principles of anti-siphoning devices. AB - BACKGROUND: Anti-siphon devices (ASDs) of various working principles were developed to overcome overdrainage-related complications associated with ventriculoperitoneal shunting. OBJECTIVE: We aimed to provide comparative data on the pressure and flow characteristics of six different types of ASDs (gravity assisted, membrane-controlled, and flow-regulated) in order to achieve a better understanding of these devices and their potential clinical application. METHODS: We analyzed three gravity-dependent ASDs (ShuntAssistant [SA], Miethke; Gravity Compensating Accessory [GCA], Integra; SiphonX [SX], Sophysa), two membrane controlled ASDs (Anti-Siphon Device [IASD], Integra; Delta Chamber [DC], Medtronic), and one flow-regulated ASD (SiphonGuard [SG], Codman). Defined pressure conditions within a simulated shunt system were generated (differential pressure 10-80 cmH2O), and the specific flow and pressure characteristics were measured. In addition, the gravity-dependent ASDs were measured in defined spatial positions (0-90 degrees ). RESULTS: The flow characteristics of the three gravity-assisted ASDs were largely dependent upon differential pressure and on their spatial position. All three devices were able to reduce the siphoning effect, but each to a different extent (flow at inflow pressure: 10 cmH2O, siphoning -20 cmH2O at 0 degrees /90 degrees : SA, 7.1 +/- 1.2*/2.3 +/- 0.5* ml/min; GCA, 10.5 +/- 0.8/3.4 +/- 0.4* ml/min; SX, 9.5 +/- 1.2*/4.7 +/- 1.9* ml/min, compared to control, 11.1 +/- 0.4 ml/min [*p < 0.05]). The flow characteristics of the remaining ASDs were primarily dependent upon the inflow pressure effect (flow at 10 cmH2O, siphoning 0 cmH2O/ siphoning -20cmH2O: DC, 2.6 +/- 0.1/ 4 +/- 0.3* ml/min; IASD, 2.5 +/- 0.2/ 0.8 +/- 0.4* ml/min; SG, 0.8 +/- 0.2*/ 0.2 +/- 0.1* ml/min [*p < 0.05 vs. control, respectively]). CONCLUSION: The tested ASDs were able to control the siphoning effect within a simulated shunt system to differing degrees. Future comparative trials are needed to determine the type of device that is superior for clinical application. PMID- 25123250 TI - Lipoic acid plays a role in scleroderma: insights obtained from scleroderma dermal fibroblasts. AB - INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and organs. Increase in oxidative stress and platelet-derived growth factor receptor (PDGFR) activation promote collagen I (Col I) production, leading to fibrosis in SSc. Lipoic acid (LA) and its active metabolite dihydrolipoic acid (DHLA) are naturally occurring thiols that act as cofactors and antioxidants, and are produced by lipoic acid synthetase (LIAS). The goal of this study was to examine whether LA and LIAS was deficient in SSc patients and determine the effect of DHLA on the phenotype of SSc dermal fibroblasts. N-acetylcysteine (NAC), a commonly used thiol antioxidant, was included as a comparison. METHODS: Dermal fibroblasts were isolated from healthy subjects and patients with diffuse cutaneous SSc. Matrix metalloproteinase (MMPs), tissue inhibitors of MMPs (TIMP), plasminogen activator inhibitor-1 (PAI 1) and LIAS were measured by ELISA. The expression of Col I was measured by immunofluorescence, hydroxyproline assay, and quantitative PCR. PDGFR phosphorylation and alpha-smooth muscle actin (alpha-SMA) was measured by Western blotting. Student's t-tests were performed for statistical analysis and p-values of less than 0.05 with two-tailed analysis were considered statistically significant. RESULTS: The expression of LA and LIAS in SSc dermal fibroblasts was lower than normal fibroblasts, however LIAS was significantly higher in SSc plasma and appeared to be released from monocytes. DHLA lowered cellular oxidative stress, and decreased PDGFR phosphorylation, Col I, PAI-1, and alpha SMA expression in SSc dermal fibroblasts. It also restored the activities of phosphatases that inactivated the PDGFR. SSc fibroblasts produced lower levels of MMP-1 and 3, and DHLA increased them. In contrast, TIMP-1 levels were higher in SSc but DHLA had minimal effect. Both DHLA and NAC increased MMP-1 activity when SSc cells were stimulated with PDGF. In general, DHLA showed better efficacy than NAC in most cases. CONCLUSIONS: DHLA not only acts as an antioxidant but also an antifibrotic since it has the ability to reverse the profibrotic phenotype of SSc dermal fibroblasts. Our study suggests that thiol antioxidants, including NAC and LA/DHLA, could be beneficial for patients with SSc. PMID- 25123253 TI - Clinical COPD Questionnaire in patients with chronic respiratory disease. AB - BACKGROUND AND OBJECTIVE: The Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (CCQ) is an easy to complete, health-related quality of life questionnaire which has been well-validated in COPD. The responsiveness of the CCQ in chronic respiratory disease patients other than COPD has not been previously described. The study aims were to determine if the CCQ in chronic respiratory disease correlates with other health related quality of life questionnaires, to assess the responsiveness of the CCQ to pulmonary rehabilitation and to determine the minimum important difference. METHODS: The CCQ, COPD Assessment Test (CAT), the Chronic Respiratory Questionnaire (CRQ) and St George's Respiratory Questionnaire (SGRQ) were measured in 138 chronic respiratory disease patients completing pulmonary rehabilitation. Change in CCQ with pulmonary rehabilitation was correlated with change in the other questionnaires. The minimum important difference of the CCQ was calculated using distribution and anchor-based approaches. RESULTS: The CCQ, CAT, CRQ and SGRQ improved significantly with rehabilitation with effect sizes of -0.43, -0.26, 0.62, -0.37. Change in CCQ correlated significantly with CAT, CRQ and SGRQ (r = 0.53, -0.64, 0.30, all P < 0.0001). The minimum important difference was -0.42 at the population level and -0.4 at the individual level. CONCLUSIONS: The CCQ is responsive to pulmonary rehabilitation in chronic respiratory disease patients, with an MID estimated at -0.4 at the individual level. PMID- 25123254 TI - Poor neonatal acid-base status in term fetuses with low cerebroplacental ratio. AB - OBJECTIVE: To determine whether small- and appropriate-for-gestational-age (SGA and AGA) term fetuses with a low cerebroplacental ratio (CPR) have worse neonatal acid-base status than those with normal CPR. METHODS: This was a retrospective study of 2927 term fetuses divided into groups according to birth-weight centile and CPR multiple of the median. The acid-base status at birth as determined by arterial and venous umbilical cord blood pH was compared between weight-centile groups with and without low CPR. RESULTS: CPR was better correlated with umbilical cord blood pH (arterial pH, r(2) = 0.008, P < 0.0001 and venous pH, r(2) = 0.01, P < 0.0001) than was birth weight (arterial pH, r(2) = 0.001, P =0.180 and venous pH, r(2) = 0.005, P < 0.001). AGA fetuses with low CPR were more academic than were those with normal CPR (P = 0.0359 and 0.0006, respectively, for arterial and venous pH). CONCLUSIONS: The findings of this study demonstrate that low CPR in AGA fetuses is an equally important marker of low neonatal pH secondary to placental underperfusion as is being SGA. Although the relative importance of low CPR and birth weight in identifying pregnancies at risk of placental hypoxemia and adverse fetal and neonatal outcome remains to be determined, this finding may be of particular value in the prediction and prevention of stillbirth and long-term neurodevelopmental disability. PMID- 25123256 TI - Similar hypotensive effects of combined aerobic and resistance exercise with 1 set versus 3 sets in women with metabolic syndrome. AB - The aim of the present study was to compare the response of systolic blood pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP) following combined training with 1 set or with 3 sets of resistance exercise (RE). Sixteen women with metabolic syndrome (MetS) were randomly assigned to perform two combined exercise protocols and a control session (CON): 1-set, 30 min of aerobic exercise (AE) at 65-70% of reserve heart rate and 1 set of 8-12 repetitions at 80% of 10-RM in six resistance exercises; 3-sets, same protocol but with 3 sets; and CON, 30 min of seated rest. The SBP, MBP and DBP were measured before and every 15 min during 90 min following the experimental sessions. The SBP displayed a decrease (P <= 0.05) during the 90 min following the RE session with 1-set and 3-set, while MBP was decreased (P <= 0.05) up to 75 min after 1-set and up to 30 min after the 3-set exercise session compared with pre-intervention values. There was a decrease in DBP only for the greatest individual decrease following 1-set (-6.1 mmHg) and 3-set (-4.9 mmHg) combined exercise sessions, without differences between them. The rate-pressure product and heart rate remained significantly higher (P <= 0.05) 75 min and 90 min after the combined exercise session with 1- and 3-sets compared with the CON, respectively. In conclusion, a low-volume RE combined with AE resulted in similar decrease of SBP when compared with RE with 3-sets in women with MetS, which could be beneficial in situations of limited time. PMID- 25123255 TI - CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases. AB - Mowat-Wilson syndrome (MWS) is characterized by moderate to severe intellectual disability and distinctive facial features in association with variable structural congenital anomalies/clinical features including congenital heart disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum, short stature, epilepsy, and microcephaly. Less common clinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These cases may be more difficult to diagnose. In this report, we add 28 MWS patients with molecular confirmation of ZEB2 mutation, including seven with an uncommon presenting feature. Among the "unusual" patients, two patients had clinical features of charge syndrome including choanal atresia, coloboma, cardiac defects, genitourinary anomaly (1/2), and severe intellectual disability; two patients had craniosynostosis; and three patients had mild intellectual disability. Sixteen patients have previously-unreported mutations in ZEB2. Genotype-phenotype correlations were suggested in those with mild intellectual disability (two had a novel missense mutation in ZEB2, one with novel splice site mutation). This report increases the number of reported patients with MWS with unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. These patients highlight the importance of facial gestalt in the accurate identification of MWS when less common features are present. PMID- 25123257 TI - Periodontal therapy for the management of cardiovascular disease in patients with chronic periodontitis. AB - BACKGROUND: There is an association between chronic periodontitis and cardiovascular disease (CVD). However, it is not known whether periodontal therapy could prevent or manage CVD in patients with chronic periodontitis. OBJECTIVES: The objective of this systematic review was to investigate the effects of periodontal therapy in preventing the occurrence of, and management or recurrence of, CVD in patients with chronic periodontitis. SEARCH METHODS: The electronic databases that were searched were the Cochrane Oral Health Group's Trials Register (to 7 April 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 3), MEDLINE via OVID (1946 to 7 April 2014), EMBASE via OVID (1980 to 7 April 2014), CINAHL via EBSCO (1937 to 7 April 2014), OpenGrey (to 7 April 2014), the Chinese BioMedical Literature Database (1978 to April 2014), the China National Knowledge Infrastructure (1994 to April 2014) and the VIP database (1989 to April 2014). We searched the US National Institutes of Health Trials Register, the World Health Organization (WHO) Clinical Trials Registry Platform and Sciencepaper Online for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs were considered eligible. Studies were selected if they included patients with a diagnosis of chronic periodontitis and previous CVD (secondary prevention studies) or no CVD (primary prevention studies); patients in the intervention group received active periodontal therapy compared to maintenance therapy, no periodontal treatment or another kind of periodontal treatment in the control group. DATA COLLECTION AND ANALYSIS: Two review authors carried out the study identification, data extraction and risk of bias assessment independently and in duplicate. Any discrepancies between the two authors were resolved by discussion or with a third review author. A formal pilot-tested data extraction form was adopted for the data extraction, and the Cochrane Collaboration's tool for risk of bias assessment was used for the critical appraisal of the literature. MAIN RESULTS: No studies were identified that assessed primary prevention of CVD in people with periodontitis. One study involving 303 participants with >= 50% blockage of one coronary artery or a coronary event within three years, but not the three months prior, was included. The study was at high risk of bias due to deviation from the protocol treatment allocation and lack of follow-up data. The trial compared scaling and root planing (SRP) with community care for a follow-up period of six to 25 months. No data on deaths (all-cause or CVD-related) were reported. There was insufficient evidence to determine the effect of SRP and community care in reducing the risk of CVD recurrence in patients with chronic periodontitis (risk ratio (RR) 0.72; 95% confidence interval (CI) 0.23 to 2.22; very low quality evidence). The effects of SRP compared with community care on high-sensitivity C-reactive protein (hs-CRP) (mean difference (MD) 0.62; -1.45 to 2.69), the number of patients with high hs-CRP (RR 0.77; 95% CI 0.32 to 1.85) and adverse events (RR 9.06; 95% CI 0.49 to 166.82) were also not statistically significant. The study did not assess modifiable cardiovascular risk factors, other blood test results, heart function parameters or revascularisation procedures. AUTHORS' CONCLUSIONS: We found very low quality evidence that was insufficient to support or refute whether periodontal therapy can prevent the recurrence of CVD in the long term in patients with chronic periodontitis. No evidence on primary prevention was found. PMID- 25123258 TI - Precession electron diffraction-assisted crystal phase mapping of metastable c GaN films grown on (001) GaAs. AB - The control growth of the cubic meta-stable nitride phase is a challenge because of the crystalline nature of the nitrides to grow in the hexagonal phase, and accurately identifying the phases and crystal orientations in local areas of the nitride semiconductor films is important for device applications. In this study, we obtained phase and orientation maps of a metastable cubic GaN thin film using precession electron diffraction (PED) under scanning mode with a point-to-point 1 nm probe size beam. The phase maps revealed a cubic GaN thin film with hexagonal GaN inclusions of columnar shape. The orientation maps showed that the inclusions have nucleation sites at the cubic GaN {111} facets. Different growth orientations of the inclusions were observed due to the possibility of the hexagonal {0001} plane to grow on any different {111} cubic facet. However, the generation of the hexagonal GaN inclusions is not always due to a 60 degrees rotation of a {111} plane. These findings show the advantage of using PED along with phase and orientation mapping, and the analysis can be extended to differently composed semiconductor thin films. PMID- 25123259 TI - Fatty acid desaturase 1 gene polymorphisms control human hepatic lipid composition. AB - Fatty acid desaturase (FADS) genes and their variants have been associated with multiple metabolic phenotypes, including liver enzymes and hepatic fat accumulation, but the detailed mechanism remains unclear. We aimed to delineate the role of FADSs in modulating lipid composition in human liver. We performed a targeted lipidomic analysis of a variety of phospholipids, sphingolipids, and ceramides among 154 human liver tissue samples. The associations between previously genome-wide association studies (GWASs)-identified six FADS single nucleotide polymorphisms (SNPs), and these lipid levels as well as total hepatic fat content (HFC) were tested. The potential function of these SNPs in regulating transcription of three FADS genes (FADS1, FADS2, and FADS3) in the locus was also investigated. We found that though these SNPs were in high linkage disequilibrium (r(2) > 0.8), the rare alleles of these SNPs were consistently and significantly associated with the accumulation of multiple long-chain fatty acids (LCFAs), with C47H85O13P (C36:4), a phosphatidylinositol (PI), and C43H80O8PN (C38:3), a phosphatidylethanolamine (PE), reached the Bonferroni corrected significance (P < 3 * 10(-4)). Meanwhile, these SNPs were significantly associated with increased ratios between the more saturated and relatively less saturated forms of LCFAs, especially between PEs, PIs, and phosphatidylcholines (PCs; P <= 3.5 * 10(-6)). These alleles were also associated with increased total HFC (P < 0.05). Further analyses revealed that these alleles were associated with decreased hepatic expression of FADS1 (P = 0.0018 for rs174556), but not FADS2 or FADS3 (P > 0.05). CONCLUSION: Our findings revealed critical insight into the mechanism underlying FADS1 and its polymorphisms in modulating hepatic lipid deposition by altering gene transcription and controlling lipid composition in human livers. PMID- 25123260 TI - Long-term phenological trends, species accumulation rates, aphid traits and climate: five decades of change in migrating aphids. AB - Aphids represent a significant challenge to food production. The Rothamsted Insect Survey (RIS) runs a network of 12.2-m suction-traps throughout the year to collect migrating aphids. In 2014, the RIS celebrated its 50th anniversary. This paper marks that achievement with an extensive spatiotemporal analysis and the provision of the first British annotated checklist of aphids since 1964. Our main aim was to elucidate mechanisms that advance aphid phenology under climate change and explain these using life-history traits. We then highlight emerging pests using accumulation patterns. Linear and nonlinear mixed-effect models estimated the average rate of change per annum and effects of climate on annual counts, first and last flights and length of flight season since 1965. Two climate drivers were used: the accumulated day degrees above 16 degrees C (ADD16) indicated the potential for migration during the aphid season; the North Atlantic Oscillation (NAO) signalled the severity of the winter before migration took place. All 55 species studied had earlier first flight trends at rate of beta = 0.611 +/- SE 0.015 days year(-1). Of these species, 49% had earlier last flights, but the average species effect appeared relatively stationary (beta = -0.010 +/- SE 0.022 days year(-1)). Most species (85%) showed increasing duration of their flight season (beta = 0.336 +/- SE 0.026 days year(-1)), even though only 54% increased their log annual count (beta = 0.002 +/- SE <0.001 year(-1)). The ADD16 and NAO were shown to drive patterns in aphid phenology in a spatiotemporal context. Early in the year when the first aphids were migrating, the effect of the winter NAO was highly significant. Further into the year, ADD16 was a strong predictor. Latitude had a near linear effect on first flights, whereas longitude produced a generally less-clear effect on all responses. Aphids that are anholocyclic (permanently parthenogenetic) or are monoecious (non-host alternating) were advancing their phenology faster than those that were not. Climate drives phenology and traits help explain how this takes place biologically. Phenology and trait ecology are critical to understanding the threat posed by emerging pests such as Myzus persicae nicotianae and Aphis fabae cirsiiacanthoidis, as revealed by the species accumulation analysis. PMID- 25123261 TI - The application of micro-vacuo-certo-contacting ophthalmophanto in X-ray radiosurgery for tumors in an eyeball. AB - The large errors of routine localization for eyeball tumors restricted X-ray radiosurgery application, just for the eyeball to turn around. To localize the accuracy site, the micro-vacuo-certo-contacting ophthalmophanto (MVCCOP) method was used. Also, the outcome of patients with tumors in the eyeball was evaluated. In this study, computed tomography (CT) localization accuracy was measured by repeating CT scan using MVCCOP to fix the eyeball in radiosurgery. This study evaluated the outcome of the tumors and the survival of the patients by follow up. The results indicated that the accuracy of CT localization of Brown-Roberts Wells (BRW) head ring was 0.65 mm and maximum error was 1.09 mm. The accuracy of target localization of tumors in the eyeball using MVCCOP was 0.87 mm averagely, and the maximum error was 1.19 mm. The errors of fixation of the eyeball were 0.84 mm averagely and 1.17 mm maximally. The total accuracy was 1.34 mm, and 95% confidence accuracy was 2.09 mm. The clinical application of this method in 14 tumor patients showed satisfactory results, and all of the tumors showed the clear rims. The site of ten retinoblastomas was decreased significantly. The local control interval of tumors were 6 ~ 24 months, median of 10.5 months. The survival of ten patients was 7 ~ 30 months, median of 16.5 months. Also, the tumors were kept stable or shrank in the other four patients with angioma and melanoma. In conclusion, the MVCCOP is suitable and dependable for X-ray radiosurgery for eyeball tumors. The tumor control and survival of patients are satisfactory, and this method can effectively postpone or avoid extirpation of eyeball. PMID- 25123262 TI - Lipase member H is a novel secreted protein associated with a poor prognosis for breast cancer patients. AB - The objective of this study is to identify the expression status and clinical implications of lipase member H (LIPH) in breast cancer in order to develop strategies for breast cancer management. LIPH expression status was detected in 346 breast cancer specimens by immunohistochemistry. The relationship between LIPH expression, clinico-pathological parameters, and prognosis of breast cancer was determined. LIPH expression was higher in breast cancer specimens than in paracarcinoma tissues (P=0.01). In total, 64.74% (224/346) of breast cancer samples had high expression of the LIPH protein. LIPH was related to tumor size, histological grade, lymph node metastasis, and distant metastasis (P=0.073, 0.001, 0.001, and 0.001, respectively). Furthermore, individuals with high LIPH expression had a significantly higher rate of distant metastasis and poorer disease-specific survival than those with no or low LIPH expression (P=0.01). A Cox regression test indicated that the LIPH protein was an independent prognostic factor (P=0.001). LIPH was differentially expressed in breast cancer individuals and is an independent prognostic factor for breast cancer as well as a potential target for its management. PMID- 25123263 TI - Matrix metalloproteinase-7 mRNA and protein expression in gastric carcinoma: a meta-analysis. AB - Messenger RNA (mRNA) acts as template for protein synthesis. The matrix metalloproteinase-7 (MMP-7) protein and its mRNA expression have been suggested to be involved in the development of various diseases and cancers. We aimed to study associations between the MMP-7 protein and mRNA expression in gastric carcinoma (GC) patients. We searched in the Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, and several Chinese databases. Studies were pooled and odds ratios and their corresponding 95 % confidence intervals were calculated. Subgroup analyses and publication bias detection were also conducted. Statistical analysis was performed via Version 12.0 STATA software. An updated meta-analysis based on 16 independent cohort studies was performed to investigate this association. The study suggests that significant differences in MMP-7 protein levels were observed in tumor-node metastasis (TNM) I-II vs. III-IV (odds radio (OR) =3.19, 95 % confidence interval (95%CI) =1.59 ~ 6.41, P=0.001), in T1-2 vs. T3-4 invasive grade (OR=1.82, 95%CI=1.07 ~ 3.12, P=0.028), and in distant metastasis-positive vs. metastasis negative samples (OR=3.14, 95%CI=1.05 ~ 9.35, P=0.040). Increased MMP-7 mRNA levels were found to be significantly correlated with invasive grade (T3-4 vs. T1 2: OR=5.61, 95%CI=2.64 ~ 11.95, P<0.001) and in the lymph node (LN) metastasis (positive vs. negative: OR=7.08, 95%CI=4.20 ~ 11.93, P<0.001) group. Country subgroup analysis yielded significantly different estimates in the protein expression of MMP-7 of all experimental groups. MMP-7 mRNA levels were increased in LN metastasis-positive GC in contrast to metastasis-negative in China and Korea (all P<0.05); this was not shown in Japan (P>0.05). Higher protein and mRNA levels of MMP-7 were statistically associated with aggressive LN metastasis, advanced TNM stage, and invasion in GC patients; MMP-7 can thus potentially serve as a useful biomarker in determining GC progression and prognosis. PMID- 25123264 TI - High expression of UCH37 is significantly associated with poor prognosis in human epithelial ovarian cancer. AB - Ubiquitin carboxyl-terminal hydrolase 37 (UCH37) is a member of deubiquitinating enzymes. It can suppress protein degradation through disassembling polyubiquitin from the distal subunit of the chain. The aim of this study was to assess the value of UCH37 in predicting tumor recurrence after curative resection in epithelial ovarian cancer (EOC) patients. In this study, the expression level of UCH37 in 5 paired EOC and normal tissue was tested by Western blot. And the association of UCH37 expression and prognostic value was analyzed in 100 tumor specimens from EOC patients, who underwent curative resection between 2003 and 2011. We found that UCH37 was up-regulated in most of the tumor tissue and high expression of UCH37 was an independent significant predictor associated with the poor outcome and recurrence of EOC (p=0.0037 and p=0.0042 in overall and disease free survival, respectively), especially in the advanced stage of EOC (p=0.0106 and p=0.0115 in overall and disease-free survival, respectively), and may become a novel predictor for prognosis of EOC patients after curative resection. Our data suggest for the first time that UCH37 overexpression is associated with advanced tumor progression and poor clinical outcome of EOC patients and may help physicians make informed decisions regarding adjuvant treatment following curative resection. PMID- 25123265 TI - Plasma interleukin-11 (IL-11) levels have diagnostic and prognostic roles in patients with pancreatic cancer. AB - Interleukin-11 (IL-11) affects inflammation, motility, and invasion in cancer. Here, we investigated the clinical significance of plasma IL-11 (IL-11p) levels in patients with pancreatic cancer. We enrolled 44 patients with pathologically confirmed diagnoses of pancreatic cancer into this study (median age at diagnosis, 68 years; range, 42-86 years), along with 30 age- and sex-matched healthy controls and 3 patients with pancreatitis complicated with pancreatic cysts and 15 patients with early pancreatitis. Median baseline IL-11p levels of patients with pancreatic cancer were significantly higher than that of the healthy controls (P < 0.001), as were those of the 15 patients with early pancreatitis. IL-11p levels presented high diagnostic accuracy for pancreatic cancer (area under the curve (AUC), 0.901; sensitivity, 97.7%; specificity, 70.0%). Age, sex, lesion site, disease stage, serum dehydrogenase, alkaline phosphatase, gamma-glutamyltransferase, and white blood cells, platelets, and hemoglobin levels did not correlate with IL-11p concentrations (P>0.05), but patients with distant metastases had lower median IL-11p values than did patients without distant metastases (P=0.043). Patients with IL-11p higher than the median level (43.2 pg/mL) had better prognoses than those with lower values (P=0.004), particularly as IL-11p concentration increased to >= 50 pg/mL (P=0.001). IL-11p concentration correlated with overall survival (>= median IL-11p, 10 months; 0.05). UCA1 can be used as a non-invasive diagnostic biomarker for TCC bladder as an adjunct to cytology in the early diagnosis of primary urinary bladder cancer. PMID- 25123268 TI - miR-203a regulates proliferation, migration, and apoptosis by targeting glycogen synthase kinase-3beta in human renal cell carcinoma. AB - MicroRNAs play a crucial role in cancer progression and metastasis. miR-203a has been identified as a tumor suppressor in various cancers. However, its functions in renal cell carcinoma have not been illustrated. In this study, we detected the miR-203a expression in renal cell carcinoma and evaluated its association with clinical features. Overexpression of miR-203a was found in renal cell carcinoma tissues and renal cell carcinoma cells. High miR-203a expression is correlated with tumor stage and short overall survival time. Bioinformatics and luciferase assay confirmed that glycogen synthase kinase-3beta was a target gene of miR 203a. Silencing of miR-203a could inhibit cell proliferation and migration, arrest them in G1 phase, and promote apoptosis in vitro. miR-203a promotes the progression of renal cell carcinoma and predicts a poor prognosis. PMID- 25123269 TI - Genetic variants in the KDR gene is associated with the prognosis of transarterial chemoembolization treated hepatocellular carcinoma. AB - Kinase insert domain receptor (KDR) is the principal receptor that promotes the proangiogenic action of vascular endothelial growth factor and is involved in the tumorigenesis and progression of many malignancies, including hepatocellular carcinoma (HCC). Single-nucleotide polymorphisms (SNPs) of KDR have been reported to be with the risk and prognosis of several malignancies. Our aim was to determine whether SNPs in KDR gene are associated with clinical outcomes in HCC patients treated with transcatheter arterial chemoembolization. A total of 192 HCC patients were tested for KDR SNPs, and the SNP results were correlated with progression-free survival (PFS) and overall survival (OS). The association of the SNPs with the overall survival (OS) of patients was assessed by Kaplan-Meier method, and then Cox proportional hazards model was used to assess the variables resulted significant at univariate analysis. No significant differences were found in correlation between KDR SNPs and patients' PFS. Our data showed that genotype AA+TA of rs1870377 and genotype CC+TC of rs2071559 were significantly associated with overall survival of HCC patients (P<0.001 and P<0.001, respectively) and remained as significant predictors for OS adjusting for high level of serum AFP (>400 MUg/L), existence of portal vein tumor thrombus, and high BCLC stage (HR=0.61; 95% CI, 0.36-0.88; P=0.003 and HR=0.54; 95% CI, 0.40 0.94; P=0.002, respectively). Our results suggest that SNPs rs1870377 and rs2071559 in the KDR gene may serve as independent prognosis biomarkers for unresectable HCC patient, which warranted further validating investigation. PMID- 25123271 TI - A systematic review and meta-analysis of perineural dexamethasone for peripheral nerve blocks. AB - We systematically reviewed the safety and efficacy of perineural dexamethasone as an adjunct for peripheral nerve blockade in 29 controlled trials of 1695 participants. We grouped trials by the duration of local anaesthetic action (short- or medium- vs long-term). Dexamethasone increased the mean (95% CI) duration of analgesia by 233 (172-295) min when injected with short- or medium term action local anaesthetics and by 488 (419-557) min when injected with long term action local anaesthetics, p < 0.00001 for both. However, these results should be interpreted with caution due to the extreme heterogeneity of results, with I2 exceeding 90% for both analyses. Meta-regression did not show an interaction between dose of perineural dexamethasone (4-10 mg) and duration of analgesia (r2 = 0.02, p = 0.54). There were no differences between 4 and 8 mg dexamethasone on subgroup analysis. PMID- 25123272 TI - Size dependence of the upconverted luminescence of NaYF4:Er,Yb microspheres for use in ratiometric thermometry. AB - The size-dependent temperature sensitivity is observed on the upconversion luminescence of NaYF4:Er,Yb microspheres with sizes between 0.7 and 2 MUm that are prepared by a poly(acrylic acid)-assisted hydrothermal process. It is found that the fluorescence intensity ratio (FIR) of their green upconversion emissions (with peaks at 521 and 539 nm) is strongly size-dependent at temperatures between 223 and 403 K. As the size of the spheres increases from 0.7 to 1.6 MUm, the maximum sensitivity decreases from 36.8 * 10(-4) to 24.7 * 10(-4) K(-1). This effect is mainly attributed to the larger specific surface area of the smaller spheres where a relatively large number of Er(III) ions are located at the surface. This results in an increase in the efficiency of the (4)S3/2 -> (2)H11/2 population process of the Er(III) ions due to stronger electron-phonon interactions with increasing T. Heating of the spheres by NIR light is also supposed to cause enhanced electron-phonon interactions in such particles. PMID- 25123270 TI - Caveolin-1 in oral squamous cell carcinoma microenvironment: an overview. AB - Caveolin-1 plays an important role in the pathogenesis of oncogenic cell transformation, tumorigenesis, and metastasis. Increased expression of caveolin-1 in an array of tumors has confirmed its value in prognosis. It has been established that oxidative stress is the main cause for loss of stromal caveolin 1 via autophagy in the tumor microenvironment. In this overview, we attempt to abridge the relationship between caveolin-1 and oral squamous cell carcinoma, taking all the established theories into consideration. PMID- 25123273 TI - Transcriptional and epigenetic networks orchestrating immune cell development and function. PMID- 25123274 TI - The role of chromatin dynamics in immune cell development. AB - In immune cells, as in all mammalian cells, nuclear DNA is wrapped around histones to form nucleosomes. The positioning and modifications of nucleosomes throughout the genome defines the chromatin state of the cell and has a large impact on gene regulation. Chromatin state is dynamic throughout immune cell development and activation. High-throughput open chromatin assays, such as DNase seq, can be used to find regulatory element across the genome and, when combined with histone modifications, can specify their function. During hematopoiesis, distal regulatory elements, known as enhancers, are established by pioneer factors that alter chromatin state. Some of these enhancers are lost, some are gained, and some are maintained as a memory of the cell's developmental origin. The enhancer landscape is unique to the cell lineage-with different enhancers regulating the same promoter-and determines the mechanism of cell type-specific activation after exposure to stimuli. Histone modification and promoter architecture govern the diverse responses to stimulation. Furthermore, chromatin dynamics may explain the high plasticity of certain tissue-resident immune cell types. Future epigenomic research will depend on the development of more efficient experiments and better methods to associate enhancers with genes. The ultimate goal of mapping genome-wide chromatin state throughout the hematopoietic tree will help illuminate the mechanisms behind immune cell development and function. PMID- 25123276 TI - Deciphering the epigenetic code of T lymphocytes. AB - The multiple lineages and differentiation states that constitute the T-cell compartment all derive from a common thymic precursor. These distinct transcriptional states are maintained both in time and after multiple rounds of cell division by the concerted actions of a small set of lineage-defining transcription factors that act in conjunction with a suite of chromatin-modifying enzymes to activate, repress, and fine-tune gene expression. These chromatin modifications collectively provide an epigenetic code that allows the stable and heritable maintenance of the T-cell phenotype. Recently, it has become apparent that the epigenetic code represents a therapeutic target for a variety of immune cell disorders, including lymphoma and acute and chronic inflammatory diseases. Here, we review the recent advances in epigenetic regulation of gene expression, particularly as it relates to the T-cell differentiation and function. PMID- 25123280 TI - Orchestration of plasma cell differentiation by Bach2 and its gene regulatory network. AB - Bach2 is a basic region-leucine zipper (bZip) transcription factor that forms heterodimers with small Maf oncoproteins and binds to target genes, thus repressing their expression. Bach2 is required for class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B cells. Bach2 represses the expression of Prdm1 encoding Blimp-1 repressor and thereby inhibits terminal differentiation of B cells to plasma cells. This causes a delay in the induction of Prdm1, thereby securing a time window for the expression of Aicda encoding activation-induced cytidine deaminase (AID) required for both CSR and SHM. Based on the characteristics of a gene regulatory network (GRN) involving Bach2 and Prdm1 and its dynamics, a 'delay-driven diversity' model was introduced to explain the responses of activated B cells. Bach2 is also required for the proper differentiation and function of peripheral T cells. In the absence of Bach2, CD4(+) T cells show increased differentiation to effector cells producing higher levels of Th2-related cytokines, such as IL-4 and IL-10, and a reduction in the generation of regulatory T cells. Bach2 represses many genes in T cells, including Prdm1, suggesting that the Bach2-Prdm1 pathway is also important in maintaining the homeostasis of T cells. Furthermore, Bach2 is essential for the function of alveolar macrophages. Therefore, Bach2 orchestrates both acquired and innate immunity at multiple points. Its connection with disease is also reviewed in this report. PMID- 25123279 TI - The regulatory network of B-cell differentiation: a focused view of early B-cell factor 1 function. AB - During the last decades, many studies have investigated the transcriptional and epigenetic regulation of lineage decision in the hematopoietic system. These efforts led to a model in which extrinsic signals and intrinsic cues establish a permissive chromatin context upon which a regulatory network of transcription factors and epigenetic modifiers act to guide the differentiation of hematopoietic lineages. These networks include lineage-specific factors that further modify the epigenetic landscape and promote the generation of specific cell types. The process of B lymphopoiesis requires a set of transcription factors, including Ikaros, PU.1, E2A, and FoxO1 to 'prime' cis-regulatory regions for subsequent activation by the B-lineage-specific transcription factors EBF1 and Pax-5. The expression of EBF1 is initiated by the combined action of E2A and FoxO1, and it is further enhanced and maintained by several positive feedback loops that include Pax-5 and IL-7 signaling. EBF1 acts in concert with Ikaros, PU.1, Runx1, E2A, FoxO1, and Pax-5 to establish the B cell-specific transcription profile. EBF1 and Pax-5 also collaborate to repress alternative cell fates and lock cells into the B-lineage fate. In addition to the functions of EBF1 in establishing and maintaining B-cell identity, EBF1 is required to coordinate differentiation with cell proliferation and survival. PMID- 25123277 TI - Transcriptional and epigenetic regulation of T-helper lineage specification. AB - Combined with TCR stimuli, extracellular cytokine signals initiate the differentiation of naive CD4(+) T cells into specialized effector T-helper (Th) and regulatory T (Treg) cell subsets. The lineage specification and commitment process occurs through the combinatorial action of multiple transcription factors (TFs) and epigenetic mechanisms that drive lineage-specific gene expression programs. In this article, we review recent studies on the transcriptional and epigenetic regulation of distinct Th cell lineages. Moreover, we review current study linking immune disease-associated single-nucleotide polymorphisms with distal regulatory elements and their potential role in the disease etiology. PMID- 25123275 TI - Transcriptional and epigenetic networks of helper T and innate lymphoid cells. AB - The discovery of the specification of CD4(+) helper T cells to discrete effector 'lineages' represented a watershed event in conceptualizing mechanisms of host defense and immunoregulation. However, our appreciation for the actual complexity of helper T-cell subsets continues unabated. Just as the Sami language of Scandinavia has 1000 different words for reindeer, immunologists recognize the range of fates available for a CD4(+) T cell is numerous and may be underestimated. Added to the crowded scene for helper T-cell subsets is the continuously growing family of innate lymphoid cells (ILCs), endowed with common effector responses and the previously defined 'master regulators' for CD4(+) helper T-cell subsets are also shared by ILC subsets. Within the context of this extraordinary complexity are concomitant advances in the understanding of transcriptomes and epigenomes. So what do terms like 'lineage commitment' and helper T-cell 'specification' mean in the early 21st century? How do we put all of this together in a coherent conceptual framework? It would be arrogant to assume that we have a sophisticated enough understanding to seriously answer these questions. Instead, we review the current status of the flexibility of helper T-cell responses in relation to their genetic regulatory networks and epigenetic landscapes. Recent data have provided major surprises as to what master regulators can or cannot do, how they interact with other transcription factors and impact global genome-wide changes, and how all these factors come together to influence helper cell function. PMID- 25123284 TI - Staying innate: transcription factor maintenance of innate lymphoid cell identity. AB - Innate and adaptive lymphocytes are characterized by phenotypic and functional characteristics that result from genomic rearrangements (in the case of antigen specific B and T cells) coupled with selective gene expression patterns that are generated in a context-dependent fashion. Cell-intrinsic expression of transcription factors (TFs) play a critical role in the regulation of gene expression that establish the distinct lymphoid subsets but also have been proposed to play an ongoing role in the maintenance of lineage-associated transcriptional signatures that comprise lymphocyte identity. This is the case for CD19(+) B cells that require Pax5 expression throughout their lifespan, as well as for diverse T-helper subsets that have specialized immune functions. Innate lymphoid cells (ILCs) comprise diverse effectors cells that differentiate under TF control and have critical roles in the early stages of immune responses. In this review, ILC development is reviewed and the requirement for persistent TF expression in the maintenance of transcriptional signatures that define ILC identity is explored. PMID- 25123283 TI - The interface between transcriptional and epigenetic control of effector and memory CD8+ T-cell differentiation. AB - Immunity to many intracellular pathogens requires the proliferation, differentiation, and function of CD8(+) cytotoxic T lymphocytes (CTLs). While the majority of effector CTLs die upon clearance of the pathogen, a small proportion of them survive to become long-lived memory CTLs. Memory CTLs can provide protective immunity against re-exposure to the same pathogen and are the principle motivation behind T-cell- based vaccine design. While a large body of cellular immunologic research has proven invaluable to define effector and memory CTLs by their different phenotypes and functions, an emerging focus in the field has been to understand how environmental cues regulate CTL differentiation on a genomic level. Genome-wide studies to profile transcriptional and epigenetic changes during infection have revealed that dynamic changes in DNA methylation patterns and histone modifications accompany transcriptional signatures that define and regulate CTL differentiation states. In this review, we emphasize the importance of epigenetic regulation of CD8(+) T-cell differentiation and the likely role that transcription factors play in this process. PMID- 25123278 TI - Innate immune regulation by STAT-mediated transcriptional mechanisms. AB - The term innate immunity typically refers to a quick but non-specific host defense response against invading pathogens. The innate immune system comprises particular immune cell populations, epithelial barriers, and numerous secretory mediators including cytokines, chemokines, and defense peptides. Innate immune cells are also now recognized to play important contributing roles in cancer and pathological inflammatory conditions. Innate immunity relies on rapid signal transduction elicited upon pathogen recognition via pattern recognition receptors (PRRs) and cell:cell communication conducted by soluble mediators, including cytokines. A majority of cytokines involved in innate immune signaling use a molecular cascade encompassing receptor-associated Jak protein tyrosine kinases and STAT (signal transducer and activator of transcription) transcriptional regulators. Here, we focus on roles for STAT proteins in three major innate immune subsets: neutrophils, macrophages, and dendritic cells (DCs). While knowledge in this area is only now emerging, understanding the molecular regulation of these cell types is necessary for developing new approaches to treat human disorders such as inflammatory conditions, autoimmunity, and cancer. PMID- 25123281 TI - Mi-2/NuRD chromatin remodeling complexes regulate B and T-lymphocyte development and function. AB - Mi-2/nucleosomal remodeling and deacetylase (NuRD) complexes are important epigenetic regulators of chromatin structure and gene expression. Mi-2/NuRD complexes are an assemblage of proteins that combine key epigenetic regulators necessary for (i) histone deacetylation and demethylation, (ii) binding to methylated DNA, (iii) mobilization of nucleosomes, and (iv) recruitment of additional regulatory proteins. Depending on their context in chromatin, Mi 2/NuRD complexes either activate or repress gene transcription. In this regard, they are important regulators of hematopoiesis and lymphopoiesis. Mi-2/NuRD complexes maintain pools of hematopoietic stem cells. Specifically, components of these complexes control multiple stages of B-cell development by regulating B cell specific transcription. With one set of components, they inhibit terminal differentiation of germinal center B cells into plasma B cells. They also mediate gene repression together with Blimp-1 during plasma cell differentiation. In cooperation with Ikaros, Mi-2/NuRD complexes also play important roles in T-cell development, including CD4 versus CD8 fate decisions and peripheral T-cell responses. Dysregulation of NuRD during lymphopoiesis promotes leukemogenesis. Here, we review general properties of Mi-2/NuRD complexes and focus on their functions in gene regulation and development of lymphocytes. PMID- 25123282 TI - Complex interactions of transcription factors in mediating cytokine biology in T cells. AB - T-helper (Th) cells play critical roles within the mammalian immune system, and the differentiation of naive CD4(+) T cells into distinct T-helper subsets is critical for normal immunoregulation and host defense. These carefully regulated differentiation processes are controlled by networks of cytokines, transcription factors, and epigenetic modifications, resulting in the generation of multiple CD4(+) T-cell subsets, including Th1, Th2, Th9, Th17, Treg, and Tfh cells. In this review, we discuss the roles of transcription factors in determining the specific type of differentiation and in particular the role of interleukin-2 (IL 2) in promoting or inhibiting Th differentiation. In addition to discussing master regulators and subset-specific transcription factors for distinct T-helper cell populations, we focus on signal transducer and activator of transcription (STAT) proteins and on the cooperative action of interferon regulatory factor 4 (IRF4) with activator protein 1 (AP-1) family proteins and STAT3 in the assembly of complexes that broadly influence T-cell differentiation. PMID- 25123286 TI - Carboxylated pillar[5]arene-coated gold nanoparticles with chemical stability and enzyme-like activity. AB - A facile synthesis of gold nanoparticles (AuNPs) covered with a multidentate macrocycle, carboxylated pillar[5]arene (CP), via a one-pot hydrothermal process is reported. The resulting AuNPs are highly stable against salts and pH variations, while their traditional counterparts are not stable at the same conditions. For the stabilization, multiple carboxylate groups of CP might contribute to electrostatic or steric stabilization. In addition, we found that CP-coated AuNPs exhibit greater peroxidase-like activity than citrate-stabilized AuNPs in the presence of silver cations. The system presented herein would provide a new scheme to fabricate unique sensory systems in combination with enzymes, which can bind to the pocket of CP. PMID- 25123287 TI - Polysaccharide-based oleogels prepared with an emulsion-templated approach. AB - The preparation and characterization of oleogels structured by using a combination of a surface-active and a non-surface-active polysaccharide through an emulsion-templated approach is reported. Specifically, the oleogels were prepared by first formulating a concentrated oil-in-water emulsion, stabilized with a combination of cellulose derivatives and xanthan gum, followed by the selective evaporation of the continuous water phase to drive the network formation, resulting in an oleogel with a unique microstructure and interesting rheological properties, including a high gel strength, G'>4000 Pa, shear sensitivity, good thixotropic recovery, and good thermostability. PMID- 25123290 TI - A search for the most accurate formula for sonographic weight estimation by fetal sex - a retrospective cohort study. AB - OBJECTIVE: The aim of this study was to assess the effect of fetal sex on the accuracy of multiple formulas for sonographic estimation fetal weight (SEFW). METHODS: The cohort included all singleton live births recorded at a single medical center from January 2004 to September 2011. The accuracy of SEFW was compared between male and female fetuses using 6575 SEFW performed within 3 days prior to delivery. Fetal weight was estimated using 27 models. RESULTS: The accuracy of different formulas in predicting birth weight of male and female fetuses was found to be significantly different in almost every accuracy index that was compared (P < 0.05). The model by Sabbagha et al. was found to be the most accurate in assessing female fetuses. The most accurate model for male fetuses was a sex-specific formula by Melamed et al. We also found that a combination of the most accurate formula for each sex to one combined sex specific model increased SEFW accuracy significantly. CONCLUSION: The accuracy of SEFW is significantly related to fetal sex. The combination of the formulas by Melamed et al. and Sabbagha et al. for male and female fetuses accordingly allowed more accurate SEFW in our research population. PMID- 25123289 TI - Metformin Restores Intermediate-Conductance Calcium-Activated K+ Channel- and Small-Conductance Calcium-Activated K+ Channel-Mediated Vasodilatation Impaired by Advanced Glycation End Products in Rat Mesenteric Artery. [Corrected]. AB - The present study was designed to investigate the effect of metformin on the impairment of intermediate-conductance and small-conductance Ca(2+)-activated potassium channels (IKCa and SKCa)-mediated relaxation in diabetes and the underlying mechanism. The endothelial vasodilatation function of mesenteric arteries was assessed with the use of wire myography. Expression levels of IKCa and SKCa and phosphorylated Thr(172) of AMP-activated protein kinase (AMPK) were measured using Western blot technology. The channel activity was observed using a whole-cell patch voltage clamp. Reactive oxygen species (ROS) were measured using dihydroethidium and 2',7'-dichlorofluorescein diacetate. Metformin restored the impairment of IKCa- and SKCa-mediated vasodilatation in mesenteric arteries from streptozotocin-induced type 2 diabetic rats and that from normal rats incubated with advanced glycation end products (AGEs) for 3 hours. In cultured human umbilical vein endothelial cells (HUVECs), 1 MUM metformin reversed AGE-induced increase of ROS and attenuated AGE- and H2O2- induced downregulation of IKCa and SKCa after long-term incubation (>24 hours). Short-term treatment (3 hours) with 1 MUM metformin reversed the decrease of IKCa and SKCa currents induced by AGE incubation for 3 hours without changing the channel expression or the AMPK activation in HUVECs. These results are the first to demonstrate that metformin restored IKCa- and SKCa-mediated vasodilatation impaired by AGEs in rat mesenteric artery, in which the upregulation of channel activity and protein expression is likely involved. PMID- 25123291 TI - On the photo-induced charge-carrier generation within monolayers of self assembled organic donor-acceptor dyads. AB - By means of STM and nc-AFM the self-assembly of a new donor-acceptor (DA) dyad molecule on highly oriented pyrolytic graphite is identified and compared to molecular simulations. Kelvin probe force microscopy (KPFM) measurements clearly show the photovoltaic activity of this model system under illumination. The optoelectronic properties and the local morphology of the DA dyad assembly are simultaneously probed by KPFM down to the level of one molecular monolayers. PMID- 25123292 TI - A facile synthesis of multi metal-doped rectangular ZnO nanocrystals using a nanocrystalline metal-organic framework template. AB - A multi metal (M: Fe, Co, and Ni)-doped rectangular ZnO nanocrystal (r-ZnO:M) was synthesised using nanocrystalline metal-organic framework-5 (n-MOF-5). After calcination in air, M-inserted n-MOF-5 led to r-ZnO:M of the wurtzite crystal structure with a small amount (<1%) of spinel ZnM2O4 phase. The inserted metal atoms of r-ZnO:M, replacing the Zn atoms of the wurtzite ZnO structure, were well dispersed throughout the nanocrystal. Density functional theory calculations not only confirm the structural stability of wurtzite r-ZnO:M and negligible contribution of spinel ZnM2O4 but also elucidate the experimentally observed increase of visible light absorbance and appearance of ferromagnetism upon metal atom doping. PMID- 25123288 TI - ABCD2 alters peroxisome proliferator-activated receptor alpha signaling in vitro, but does not impair responses to fenofibrate therapy in a mouse model of diet induced obesity. AB - Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) alpha ligand that has been widely used as a lipid-lowering agent in the treatment of hypertriglyceridemia. ABCD2 (D2) is a peroxisomal long-chain acyl-CoA transporter that is highly induced by fenofibrate in the livers of mice. To determine whether D2 is a modifier of fibrate responses, wild-type and D2-deficient mice were treated with fenofibrate for 14 days. The absence of D2 altered expression of gene clusters associated with lipid metabolism, including PPARalpha signaling. Using 3T3-L1 adipocytes, which express high levels of D2, we confirmed that knockdown of D2 modified genomic responses to fibrate treatment. We next evaluated the impact of D2 on effects of fibrates in a mouse model of diet induced obesity. Fenofibrate treatment opposed the development of obesity, hypertriglyceridemia, and insulin resistance. However, these effects were unaffected by D2 genotype. We concluded that D2 can modulate genomic responses to fibrates, but that these effects are not sufficiently robust to alter the effects of fibrates on diet-induced obesity phenotypes. PMID- 25123285 TI - ID'ing innate and innate-like lymphoid cells. AB - The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B- and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. PMID- 25123293 TI - Water-stable zirconium-based metal-organic framework material with high-surface area and gas-storage capacities. AB - We designed, synthesized, and characterized a new Zr-based metal-organic framework material, NU-1100, with a pore volume of 1.53 ccg(-1) and Brunauer Emmett-Teller (BET) surface area of 4020 m(2) g(-1) ; to our knowledge, currently the highest published for Zr-based MOFs. CH4 /CO2 /H2 adsorption isotherms were obtained over a broad range of pressures and temperatures and are in excellent agreement with the computational predictions. The total hydrogen adsorption at 65 bar and 77 K is 0.092 g g(-1) , which corresponds to 43 g L(-1) . The volumetric and gravimetric methane-storage capacities at 65 bar and 298 K are approximately 180 vSTP /v and 0.27 g g(-1) , respectively. PMID- 25123294 TI - Lasting personality pathology following exposure to catastrophic trauma in adults: systematic review. AB - BACKGROUND: By definition, personality disorders (PDs) are evident in late childhood and adolescence, but evidence for personality pathology occurring after adolescence is unclear. AIM: We aimed to review extant literature on personality change following exposure to catastrophic trauma in adults in order to identify the prevalence and clinical features of any long-term personality pathology. METHOD: Relevant studies were identified by searching three bibliographic databases (MEDLINE, EMBASE and PsychINFO) from inception to November 2011 using terms related to personality and trauma. RESULTS: No prospective studies that investigated long-term personality change following exposure to trauma in adults were found. Two retrospective studies reported the prevalence of enduring personality change of 2.6% and 6% (weighted prevalence 4.6%, 95% confidence interval 3.4-6.3%), and one study reported 20% increase in adult-onset antisocial behaviour following exposure to trauma. Findings from cross-sectional studies that examined the prevalence of PDs in people exposed to catastrophic trauma reported that Cluster C and Cluster A were the most common with avoidant, paranoid and obsessive-compulsive PDs among those most frequently reported. CONCLUSION: A minority of adults who are exposed to severe trauma appear to go on to develop significant personality pathology. The observed personality disturbance is multifarious and more extensive than the prototype described in ICD-10. PMID- 25123296 TI - Maximum likelihood estimation of FRET efficiency and its implications for distortions in pixelwise calculation of FRET in microscopy. AB - Ratiometric determination of the efficiency of fluorescence or Forster resonance energy transfer (FRET) is one of the most widespread methods for the characterization of protein clustering and conformation. Low photon numbers, often present in pixel-by-pixel determination of FRET efficiency in digital microscopy, result in large uncertainties in the derived FRET parameter. Here, we propose a method based on maximum likelihood estimation (MLE) of FRET efficiency using photon counting detectors to overcome this limitation. Intensities measured in the donor, FRET, and acceptor channels were all assumed to follow Poisson statistics as a result of detector shot noise. The joint probability of photon numbers detected in the donor, FRET, and acceptor channels was derived using an equation describing the relationship between the three measured intensities. The FRET efficiency generating the measured photon numbers with the largest likelihood was determined iteratively providing a single FRET value for all pixels in the calculation. Since as few as 100 pixels are sufficient to provide a maximum likelihood estimate for FRET, biological variability in FRET values can be revealed by performing the analysis for regions of interests in an image. Since the algorithm provides the probability of a combination of donor, FRET, and acceptor intensities observed in each individual pixel given a certain FRET efficiency, outlier pixels with low probabilities could be excluded from the analysis. Simulations carried out with low photon numbers in the presence and absence of outlier pixels revealed that the proposed approach can reliably and reproducibly estimate FRET efficiency. In addition, systematic evaluation of the simulation results showed that the distribution of pixel-by-pixel FRET efficiencies is skewed, and the mean of these FRET values is a biased and unreliable estimate of the FRET efficiency. In the absence of outlier pixels, FRET calculated from summed donor, FRET, and acceptor intensities proved to be as reliable as MLE. We conclude that MLE of FRET outperforms calculations using summed and pixel-by-pixel intensities in biologically relevant situations involving low photon numbers and outlier pixels. (c) 2014 International Society for Advancement of Cytometry. PMID- 25123295 TI - A multicentre randomized trial of the treatment of patients with pemphigus vulgaris with infliximab and prednisone compared with prednisone alone. AB - BACKGROUND: Pemphigus vulgaris (PV) is a blistering disease and tumour necrosis factor-alpha has a role in its pathogenesis. OBJECTIVES: To evaluate the safety of infliximab (IFX) with prednisone compared with prednisone alone in the treatment of PV. In addition, treatment response was assessed and mechanistic studies were performed. METHODS: Subjects with PV who had ongoing disease activity while being maintained on prednisone were randomized to receive either IFX or placebo in addition to prednisone. Response status and immunoglobulin (Ig) G anti-desmoglein (Dsg)1 and Dsg3 antibodies were assessed at 18 and 26 weeks. RESULTS: Ten subjects were randomized to each group. There were no safety signals during the course of the study. At week 18, one subject in each group had responded. At week 26, three IFX-treated subjects vs. none in the placebo group had responded (P = 0.21). At weeks 18 and 26, the median IgG anti-Dsg1 and anti Dsg3 levels were lower in the IFX-treated patients [IgG anti-Dsg-1 (week 18, P = 0.035; week 26, P = 0.022); IgG anti-Dsg3 (week 18, P = 0.035; week, 26 P = 0.05)]. CONCLUSIONS: This study is limited by the relatively small sample size. There was no significant difference between study arms in the proportion of subjects with treatment-related adverse events > grade 3. IFX therapy was not shown to be effective for the treatment of patients with PV in this randomized, placebo-controlled trial, although IFX treatment may be associated with a decrease in anti-Dsg1 and Dsg3 antibodies. PMID- 25123298 TI - Patient-reported outcomes of dental implant therapy in a large randomly selected sample. AB - BACKGROUND: In addition to traditional clinical parameters, the need to include patient-reported assessments into dental implant research has been emphasized. AIM: The aim of this study was to evaluate patient-reported outcomes following implant-supported restorative therapy in a randomly selected patient sample. MATERIAL AND METHODS: Four thousand seven hundred and sixteen patients were randomly selected from the data register of the Swedish Social Insurance Agency. A questionnaire containing 10 questions related to implant-supported restorative therapy was mailed to each of the individuals about 6 years after therapy. Associations between questionnaire data, and (i) patient-related, (ii) clinician related and (iii) therapy-related variables were identified by multivariate analyses. RESULTS: Three thousand eight hundred and twenty-seven patients (81%) responded to the questionnaire. It was demonstrated that the overall satisfaction among patients was high. Older patients presented with an overall more positive perception of the results of the therapy than younger patients and males were more frequently satisfied in terms of esthetics than females. While clinical setting did not influence results, patients treated by specialist dentists as opposed to general practitioners reported a higher frequency of esthetic satisfaction and improved chewing ability. In addition, patients who had received extensive implant-supported reconstructions, in contrast to those with small reconstructive units, reported more frequently on improved chewing ability and self-confidence but also to a larger extent on implant-related complications. CONCLUSION: It is suggested that patient-perceived outcomes of implant-supported restorative therapy are related to (i) age and gender of the patient, (ii) the extent of restorative therapy and (iii) the clinician performing the treatment. PMID- 25123303 TI - Building up a chemical proteomics network in Europe and beyond. PMID- 25123297 TI - Tumor genome analysis includes germline genome: are we ready for surprises? AB - We sought to describe the spectrum of potential and confirmed germline genomic events incidentally identified during routine medium-throughput somatic tumor DNA sequencing, and to provide a framework for pre- and post-test consent and counseling for patients and families. Targeted tumor-only next-generation sequencing (NGS) had been used to evaluate for possible druggable genomic events obtained from consecutive new patients with metastatic gastroesophageal, hepatobiliary or colorectal cancer seen at the University of Chicago. A panel of medical oncologists, cancer geneticists and genetic counselors retrospectively grouped these patients (N = 111) based on probability of possessing a potentially inherited mutation in a cancer susceptibility gene, both prior to and after incorporating tumor-only NGS results. High-risk patients (determined from NGS results) were contacted and counseled in person by a genetic counselor (N = 21). When possible and indicated, germline genetic testing was offered. Of 8 evaluable high-risk patients, 7 underwent germline testing. Three (37.5%) had confirmed actionable germline mutations (all in the BRCA2 gene). NGS offers promise, but poses significant challenges for oncologists who are ill prepared to handle incidental findings that have clinical implications for at risk family members. In this relatively small cohort of patients undergoing tumor genomic testing for gastrointestinal malignancies, we incidentally identified 3 BRCA2 mutations carriers. This report underscores the need for oncologists to develop a framework for pre- and post-test communication of risks to patients undergoing routine tumor-only sequencing. PMID- 25123302 TI - Carlos F. Barbas III (1964-2014): Visionary at the interface of chemistry and biology. PMID- 25123304 TI - Report from the Third Annual Symposium of the RIKEN-Max Planck Joint Research Center for Systems Chemical Biology. AB - The third Annual Symposium of the RIKEN-Max Planck Joint Research Center for Systems Chemical Biology was held at Ringberg castle, May 21-24, 2014. At this meeting 45 scientists from Japan and Germany presented the latest results from their research spanning a broad range of topics in chemical biology and glycobiology. PMID- 25123305 TI - The pathology of bowel cancer screening. AB - Colorectal cancer screening is widely promulgated in many parts of the world and population screening is occurring in many countries, especially in western Europe. Although, intuitively, it might be thought that the pathology resulting from screening should be straightforward, being mainly that of polyp diagnosis and the biopsy diagnosis and staging of established adenocarcinoma, in fact experience has shown that there are several areas of considerable difficulty and controversy. In the UK somewhat different programmes, all based on faecal occult blood (FOB) screening, have been developed and each has generated similar pathological conundra. These include the biopsy diagnosis of adenocarcinoma, colorectal serrated pathology, the diagnosis and management of polyp cancers and last, but certainly not least, the phenomenon of the large sigmoid colonic adenomatous polyp with epithelial misplacement/pseudo-invasion. Polyp cancers provide especially difficult management conundra and discussion of that management within a multidisciplinary team-based management meeting is regarded as essential in the UK. Large adenomatous polyps of the sigmoid colon with epithelial misplacement are selected into FOB-based screening programmes and have provided extraordinary diagnostic challenges. Finally, the quality assurance procedures introduced for screening can ensure a considerable overall improvement in the quality of lower gastrointestinal tract pathological reporting. PMID- 25123306 TI - Effects of cortical microstimulation on confidence in a perceptual decision. AB - Decisions are often associated with a degree of certainty, or confidence--an estimate of the probability that the chosen option will be correct. Recent neurophysiological results suggest that the central processing of evidence leading to a perceptual decision also establishes a level of confidence. Here we provide a causal test of this hypothesis by electrically stimulating areas of the visual cortex involved in motion perception. Monkeys discriminated the direction of motion in a noisy display and were sometimes allowed to opt out of the direction choice if their confidence was low. Microstimulation did not reduce overall confidence in the decision but instead altered confidence in a manner that mimicked a change in visual motion, plus a small increase in sensory noise. The results suggest that the same sensory neural signals support choice, reaction time, and confidence in a decision and that artificial manipulation of these signals preserves the quantitative relationship between accumulated evidence and confidence. PMID- 25123308 TI - Separate microcircuit modules of distinct v2a interneurons and motoneurons control the speed of locomotion. AB - Spinal circuits generate locomotion with variable speed as circumstances demand. These circuits have been assumed to convey equal and uniform excitation to all motoneurons whose input resistance dictates their activation sequence. However, the precise connectivity pattern between excitatory premotor circuits and the different motoneuron types has remained unclear. Here, we generate a connectivity map in adult zebrafish between the V2a excitatory interneurons and slow, intermediate, and fast motoneurons. We show that the locomotor network does not consist of a uniform circuit as previously assumed. Instead, it can be deconstructed into three separate microcircuit modules with distinct V2a interneuron subclasses driving slow, intermediate, or fast motoneurons. This modular design enables the increase of locomotor speed by sequentially adding microcircuit layers from slow to intermediate and fast. Thus, this principle of organization of vertebrate spinal circuits represents an intrinsic mechanism to increase the locomotor speed by incrementally engaging different motor units. PMID- 25123307 TI - The crystal structure of netrin-1 in complex with DCC reveals the bifunctionality of netrin-1 as a guidance cue. AB - Netrin-1 is a guidance cue that can trigger either attraction or repulsion effects on migrating axons of neurons, depending on the repertoire of receptors available on the growth cone. How a single chemotropic molecule can act in such contradictory ways has long been a puzzle at the molecular level. Here we present the crystal structure of netrin-1 in complex with the Deleted in Colorectal Cancer (DCC) receptor. We show that one netrin-1 molecule can simultaneously bind to two DCC molecules through a DCC-specific site and through a unique generic receptor binding site, where sulfate ions staple together positively charged patches on both DCC and netrin-1. Furthermore, we demonstrate that UNC5A can replace DCC on the generic receptor binding site to switch the response from attraction to repulsion. We propose that the modularity of binding allows for the association of other netrin receptors at the generic binding site, eliciting alternative turning responses. PMID- 25123309 TI - Amygdala-dependent fear memory consolidation via miR-34a and Notch signaling. AB - Using an array-based approach after auditory fear conditioning and microRNA (miRNA) sponge-mediated inhibition, we identified a role for miR-34a within the basolateral amygdala (BLA) in fear memory consolidation. Luciferase assays and bioinformatics suggested the Notch pathway as a target of miR-34a. mRNA and protein levels of Notch receptors and ligands are downregulated in a time- and learning-specific manner after fear conditioning in the amygdala. Systemic and stereotaxic manipulations of the Notch pathway indicated that Notch signaling in the BLA suppresses fear memory consolidation. Impairment of fear memory consolidation after inhibition of miR-34a within the BLA is rescued by inhibiting Notch signaling. Together, these data suggest that within the BLA, a transient decrease in Notch signaling, via miR-34a regulation, is important for the consolidation of fear memory. This work expands the idea that developmental molecules have roles in adult behavior and that existing interventions targeting them hold promise for treating neuropsychiatric disorders. VIDEO ABSTRACT: PMID- 25123310 TI - Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. AB - Human induced pluripotent stem cells (iPSCs) from a healthy 86-year-old male were differentiated into neural stem cells and grafted into adult immunodeficient rats after spinal cord injury. Three months after C5 lateral hemisections, iPSCs survived and differentiated into neurons and glia and extended tens of thousands of axons from the lesion site over virtually the entire length of the rat CNS. These iPSC-derived axons extended through adult white matter of the injured spinal cord, frequently penetrating gray matter and forming synapses with rat neurons. In turn, host supraspinal motor axons penetrated human iPSC grafts and formed synapses. These findings indicate that intrinsic neuronal mechanisms readily overcome the inhibitory milieu of the adult injured spinal cord to extend many axons over very long distances; these capabilities persist even in neurons reprogrammed from very aged human cells. VIDEO ABSTRACT: PMID- 25123311 TI - Network structure within the cerebellar input layer enables lossless sparse encoding. AB - The synaptic connectivity within neuronal networks is thought to determine the information processing they perform, yet network structure-function relationships remain poorly understood. By combining quantitative anatomy of the cerebellar input layer and information theoretic analysis of network models, we investigated how synaptic connectivity affects information transmission and processing. Simplified binary models revealed that the synaptic connectivity within feedforward networks determines the trade-off between information transmission and sparse encoding. Networks with few synaptic connections per neuron and network-activity-dependent threshold were optimal for lossless sparse encoding over the widest range of input activities. Biologically detailed spiking network models with experimentally constrained synaptic conductances and inhibition confirmed our analytical predictions. Our results establish that the synaptic connectivity within the cerebellar input layer enables efficient lossless sparse encoding. Moreover, they provide a functional explanation for why granule cells have approximately four dendrites, a feature that has been evolutionarily conserved since the appearance of fish. PMID- 25123313 TI - Unique interweaved microtubule scaffold mediates osmosensory transduction via physical interaction with TRPV1. AB - The electrical activity of mammalian osmosensory neurons (ONs) is increased by plasma hypertonicity to command thirst, antidiuretic hormone release, and increased sympathetic tone during dehydration. Osmosensory transduction is a mechanical process whereby decreases in cell volume cause the activation of transient receptor potential vanilloid type-1 (TRPV1) channels to induce depolarization and increase spiking activity in ONs. However, it is not known how cell shrinking is mechanically coupled to channel activation. Using superresolution imaging, we found that ONs are endowed with a uniquely interweaved scaffold of microtubules throughout their somata. Microtubules physically interact with the C terminus of TRPV1 at the cell surface and provide a pushing force that drives channels activation during shrinking. Moreover, we found that changes in the density of these interactions can bidirectionally modulate osmosensory gain. Microtubules are thus an essential component of the vital neuronal mechanotransduction apparatus that allows the brain to monitor and correct body hydration. PMID- 25123312 TI - Dnmt3a regulates global gene expression in olfactory sensory neurons and enables odorant-induced transcription. AB - During differentiation, neurons exhibit a reorganization of DNA modification patterns across their genomes. The de novo DNA methyltransferase Dnmt3a is implicated in this process, but the effects of its absence have not been fully characterized in a purified neuronal population. To better understand how DNA modifications contribute to neuronal function, we performed a comprehensive analysis of the epigenetic and transcriptional landscapes of Dnmt3a-deficient mature olfactory sensory neurons (mOSNs), the primary sensory neurons of the olfactory epithelium. Dnmt3a is required for both 5-methylcytosine and 5 hydroxymethylcytosine patterning within accessible genomic regions, including hundreds of neurodevelopmental genes and neural enhancers. Loss of Dnmt3a results in the global disruption of gene expression via activation of silent genes and reduction of mOSN-expressed transcripts. Importantly, the DNA modification state and inducibility of odorant-activated genes are markedly impaired in Dnmt3a knockouts, suggesting a crucial role for this enzyme in establishing an epigenetic landscape compatible with neuronal plasticity. PMID- 25123315 TI - [Pulmonary hypertension in internal medicine]. PMID- 25123316 TI - [Intervention research in public health. Methodological and legal aspects of collective interventions]. PMID- 25123314 TI - The Drosophila IR20a clade of ionotropic receptors are candidate taste and pheromone receptors. AB - Insects use taste to evaluate food, hosts, and mates. Drosophila has many "orphan" taste neurons that express no known taste receptors. The Ionotropic Receptor (IR) superfamily is best known for its role in olfaction, but virtually nothing is known about a clade of ~35 members, the IR20a clade. Here, a comprehensive analysis of this clade reveals expression in all taste organs of the fly. Some members are expressed in orphan taste neurons, whereas others are coexpressed with bitter- or sugar-sensing Gustatory receptor (Gr) genes. Analysis of the closely related IR52c and IR52d genes reveals signatures of adaptive evolution, roles in male mating behavior, and sexually dimorphic expression in neurons of the male foreleg, which contacts females during courtship. These neurons are activated by conspecific females and contact a neural circuit for sexual behavior. Together, these results greatly expand the repertoire of candidate taste and pheromone receptors in the fly. PMID- 25123317 TI - [Pulmonary hypertension in chronic respiratory diseases]. AB - Pulmonary hypertension is frequent in advanced chronic respiratory diseases, with an estimated prevalence at the time of pulmonary transplantation of 30-50 % in idiopathic pulmonary fibrosis, 30-50 % in chronic obstructive pulmonary disease, 50 % in combined pulmonary fibrosis and emphysema, 75 % in sarcoidosis, and more than 75 % of cases in pulmonary Langerhans cell histiocytosis. Histologic features include varying degrees of pulmonary arterial remodeling (prominent), vascular rarefaction (emphysema), fibrosis or specific involvement of the pulmonary arteries (idiopathic pulmonary fibrosis, sarcoidosis, lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis), in situ thrombosis, and frequently associated involvement of the pulmonary veins (idiopathic pulmonary fibrosis, sarcoidosis). Pulmonary hypertension is usually detected using echocardiography with Doppler, however right heart catheterisation is required to confirm precapillary pulmonary hypertension defined by pulmonary artery pressure >= 25 mm Hg, with pulmonary artery wedge pressure <= 15 mm Hg. When present, it is associated with decreased exercise capacity and worse mortality. Pulmonary hypertension in chronic respiratory disease is almost invariably multifactorial; hypoxia is one of its main determinants, however supplemental oxygen therapy rarely reverses pulmonary hypertension. Management of pulmonary hypertension in chronic respiratory disease is mostly based on the optimal treatment of the underlying disease. Available data do not support the use of drug therapies specific for pulmonary hypertension in the setting of chronic respiratory diseases, however very few clinical studies have been conducted so far specifically in this context. PMID- 25123318 TI - Increasing occurrence of choledochal malformations in children: a single-center 37-year experience from Finland. AB - OBJECTIVE: Few reports on choledochal malformations (CMs) in European populations exist. MATERIALS AND METHODS: The medical records of pediatric CM patients managed in our nationwide referral center for pediatric hepatobiliary surgery between 1976 and 2013 (n = 38; 71% females) were reviewed. RESULTS: Over follow up time, the relative proportion of fusiform CMs increased significantly (p = 0.007) and the estimated total incidence rose from 1:128,000 to 1:38,000 (p = 0.017). Cystic CMs (42%) presented at younger age than fusiform CMs (47%) (0.8 vs. 4.6 years, p = 0.001). Two-thirds had abdominal pain and half were cholestatic at presentation. Pancreatitis had occurred in 16%. In addition to ultrasound, 71% underwent magnetic resonance cholangiopancreatography and 39% underwent endoscopic retrograde cholangiopancreatography. Median CM dilatation was 15 (10-28) mm and a 12 (9-13) mm long common pancreaticobiliary channel was confirmed in 61%, increasingly during recent years. Intrahepatic biliary tree was dilated in 19%, whereas main ducts were dilated in 50%. Apart from two operated in the 1970s and one with choledochocele, patients underwent resection of extrahepatic bile ducts with Roux-en-Y hepaticojejunostomy at age of 4.2 (0.8 9.2) years. Postoperative bile leakage and hemorrhage required reoperations in two. At last follow-up 4.8 (1.3-13.2) years postoperatively, none had dilated intrahepatic biliary ducts or elevated plasma bilirubin (5 [3-7] umol/l). Single cholangitis episodes had occurred in two, whereas others were asymptomatic. CONCLUSION: CM incidence has increased significantly in Finland, being currently over threefold higher than previous estimates in the Western world would suggest. Removal of the extrahepatic biliary tree with hepaticojejunostomy for type I and IV CMs yielded excellent results. PMID- 25123320 TI - Narrowing the cystoscopy gap. PMID- 25123319 TI - Kinetic and stoichiometric characterization of organoautotrophic growth of Ralstonia eutropha on formic acid in fed-batch and continuous cultures. AB - Formic acid, acting as both carbon and energy source, is a safe alternative to a carbon dioxide, hydrogen and dioxygen mix for studying the conversion of carbon through the Calvin-Benson-Bassham (CBB) cycle into value-added chemical compounds by non-photosynthetic microorganisms. In this work, organoautotrophic growth of Ralstonia eutropha on formic acid was studied using an approach combining stoichiometric modeling and controlled cultures in bioreactors. A strain deleted of its polyhydroxyalkanoate production pathway was used in order to carry out a physiological characterization. The maximal growth yield was determined at 0.16 Cmole Cmole(-1) in a formate-limited continuous culture. The measured yield corresponded to 76% to 85% of the theoretical yield (later confirmed in pH controlled fed-batch cultures). The stoichiometric study highlighted the imbalance between carbon and energy provided by formic acid and explained the low growth yields measured. Fed-batch cultures were also used to determine the maximum specific growth rate (MUmax = 0.18 h(-1) ) and to study the impact of increasing formic acid concentrations on growth yields. High formic acid sensitivity was found in R eutropha since a linear decrease in the biomass yield with increasing residual formic acid concentrations was observed between 0 and 1.5 g l(-1) . PMID- 25123321 TI - Harnessing big data for health care and research: are urologists ready? AB - We are at a crossroads in terms of the data we collect and how they are analyzed. In health care, big data analytics may uncover associations, patterns, and trends with the potential to advance patient care and lower costs. To adapt to this approach, urologists will have to ask the right questions. PMID- 25123322 TI - Robotics: Will they give a new kick to single-site surgery? PMID- 25123323 TI - The development of prognostic and predictive biomarkers in renal cell cancer are not one and the same thing. PMID- 25123324 TI - Editorial. PMID- 25123326 TI - Increasing the sensitivity of endocervical curettings by performing ThinPrep(r) Pap on transport container fluid: is diagnostic material going down the drain? AB - OBJECTIVE: The sensitivity of endocervical curettage (ECC) can be suboptimal because of limited epithelial tissue. The false-negative rate for ECC in patients with cervical intraepithelial neoplasia involving the endocervical canal has been reported to be 45%. ECC samples are transported to pathology in formalin- or saline-filled containers; this fluid is discarded after the specimen has been submitted. We evaluated the utility of performing liquid-based cytological preparations from ECC transport container fluid as a way to increase the sensitivity of ECC specimens. METHODS: Consecutive ECC specimens received at one of the two participating institutions were selected prospectively. A surgical pathology mesh bag was placed over a ThinPrep((r)) CytoLyt((r)) solution container, and the specimen was filtered through the bag, collecting the transport fluid in the container. The CytoLyt((r)) was processed to obtain a container fluid ThinPrep((r)) (CF-TP) liquid-based Papanicolaou (Pap) slide. The CF-TP slides were reviewed and the findings were compared with those from the ECC and follow-up specimens. RESULTS: The cohort included 53 patients. Discrepancies between CF-TP and ECC were seen in 14 of the 53 patients (26%); a more significant lesion was identified in CF-TP relative to ECC in 13 of these cases. CF-TP diagnosis was confirmed in eight of 11 cases with histological follow-up. A positive CF-TP result was confirmed by histology in six of nine cases with negative ECC. CONCLUSIONS: Combining the pathological evaluation of ECC specimens with liquid-based cytology performed on the transport container fluid can increase the diagnostic sensitivity of the ECC procedure for the detection of cervical lesions. PMID- 25123327 TI - Investigations on a wheat bran biorefinery involving organosolv fractionation and enzymatic treatment. AB - The present study elucidates the organosolv treatment of wheat bran, the major by product of the milling industry. The influence of temperature (160-200 degrees C) and ethanol concentration (30-60% (w/w)) at a given process time of 30min was investigated. Enzymatic treatments of the organosolv extracts including solid residues led to an overall glucose yield of 75%. The conversion of hemicelluloses into xylose and arabinose was approximately 60% and 45%, respectively. Proteins could be almost completely dissolved, however, practically no free amino acids were obtained. Surprisingly, only around 30% of lignin and 65% of minerals were dissolved. Severe treatment conditions induced the disintegration of fat into glycerol and fatty acids as well as the formation of sugar degradation products. During the lignin precipitation step, proteins partially coprecipitated. PMID- 25123329 TI - Normovolemic hemodilution using hydroxyethyl starch 130/0.4 (Voluven) in a Jehovah's Witness child requiring cardiopulmonary bypass for ventricular septal defect repair. AB - Surgical repair of congenital heart disease during cardiopulmonary bypass is common, and performing these complicated procedures in the absence of blood transfusions is especially challenging. A case of a Jehovah's Witness child who underwent surgical repair of a ventricular septal defect utilizing a new tetrastarch for autologous normovolemic hemodilution is reported. A successful operative repair was achieved without the need for non-autologous blood transfusion. PMID- 25123328 TI - Speeded manual responses to unseen visual stimuli in hemianopic patients: what kind of blindsight? AB - Blindsight, i.e., unconscious visually guided behaviour triggered by stimuli presented to a cortically blind hemifield, has been typically found either by using direct (forced choice) or indirect (interhemispheric) methods. However, one would expect to find blindsight also in fast responses to suddenly appearing visual stimuli, a reminiscence of evolutionary ancient adaptive behaviour. In this study we provide preliminary evidence of this form of blindsight by using a conservative method for assessing blindsight based on a comparison between the cumulative probability functions (CPFs) of simple reaction times to blind and intact field stimuli. Furthermore, in two patients with blindsight we provided evidence that their above-chance unconscious responses were likely to be triggered by the intact hemisphere. PMID- 25123330 TI - Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in Auckland, New Zealand. AB - Hand-foot-and-mouth disease is a common, usually mild childhood illness caused by enteroviruses. Over the last five years, coxsackievirus A6 has been identified as a causative agent in outbreaks in Europe, South-East Asia and America. It has an atypical presentation compared with other enteroviruses, with more widespread rash, larger blisters and subsequent skin peeling and/or nail shedding. We give the first description of an outbreak of coxsackievirus A6 in New Zealand and how health-care communication networks enabled detection of and dissemination of information about this emergent strain. PMID- 25123331 TI - Frequency of thrombotic risk factors in Chinese familial Budd-Chiari Syndrome. PMID- 25123332 TI - Serum soluble CD40 Ligand levels are associated with severity and mortality of brain trauma injury patients. AB - BACKGROUND: Serum soluble CD40 Ligand (sCD40L) levels, which exhibit prothrombotic and proinflammatory properties, have not been studied in patients with traumatic brain injury (TBI). Thus, the objective of this study was to determine whether serum sCD40L levels are associated with severity and mortality in patients with severe TBI. METHODS: This was a prospective, observational and multicenter study carried out in six Spanish Intensive Care Units. Patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9 were included, while those with Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Serum levels of sCD40L were measured on the day of TBI. Endpoint was established in 30-day mortality. RESULTS: We found higher serum sCD40L levels (P<0.001) in non-surviving TBI patients (N=27) than in survivor ones (N=73). Logistic regression analysis showed that serum sCD40L levels were associated with 30-day mortality (OR=1.58; 95% CI=1.12-2.21; P=0.008) controlling for APACHE-II score and computer tomography findings. The area under the curve (AUC) for serum sCD40L levels as predictor of 30-day mortality was 0.79 (95% CI=0.70-0.86; P<0.001). Survival analysis showed that patients with serum sCD40L levels higher than 2.11 ng/mL presented increased 30-day mortality than patients with lower levels (Hazard ratio=9.0; 95% CI=4.25-19.27; P<0.001). We found an association between serum sCD40L levels and APACHE-II (rho=0.33; P=0.001), and GCS score (rho=-0.21; P=0.04). CONCLUSIONS: To our knowledge, this is the first study reporting data on serum sCD40L levels in patients with severe TBI. The most relevant and newer findings of our study are that serum sCD40L levels in non surviving patients with severe TBI are higher than in surviving ones, and that there are an association between serum sCD40L levels and TBI severity and mortality. PMID- 25123334 TI - High exposure to erlotinib and severe drug-induced interstitial lung disease in patients with non-small-cell lung cancer. PMID- 25123333 TI - Interval lung cancers not detected on screening chest X-rays: How are they different? AB - BACKGROUND: The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial provides us an opportunity to describe interval lung cancers not detected by screening chest X-ray (CXR) compared to screen-detected cancers. METHODS: Participants were screened for lung cancer with CXR at baseline and annually for two (never smokers) or three (ever smokers) more years. Screen-detected cancers were those with a positive CXR and diagnosed within 12 months. Putative interval cancers were those with a negative CXR screen but with a diagnosis of lung cancer within 12 months. Potential interval cancers were re-reviewed to determine whether lung cancer was missed and probably present during the initial interpretation or whether the lesion was a "true interval" cancer. RESULTS: 77,445 participants were randomized to the intervention arm with 70,633 screened. Of 5227 positive screens from any screening round, 299 resulted in screen detected lung cancers; 151 had potential interval cancers with 127 CXR available for re-review. Cancer was probably present in 45/127 (35.4%) at time of screening; 82 (64.6%) were "true interval" cancers. Compared to screen-detected cancers, true interval cancers were more common among males, persons with <12 years education and those with a history of smoking. True interval lung cancers were more often small cell, 28.1% vs. 7.4%, and less often adenocarcinoma, 25.6% vs. 56.2% (p<0.001), more advanced stage IV (30.5% vs. 16.6%, p<0.02), and less likely to be in the right upper lobe, 17.1% vs. 36.1% (p<0.02). CONCLUSION: True interval lung cancers differ from CXR-screen-detected cancers with regard to demographic variables, stage, cell type and location. ClinicalTrials.gov number: NCT00002540. PMID- 25123335 TI - [Pushing the boundaries: How stereotactic irradiation offers new hope for treatment]. PMID- 25123337 TI - Metabolic syndrome and peripheral arterial disease. PMID- 25123336 TI - Analysis in conditional cannabinoid 1 receptor-knockout mice reveals neuronal subpopulation-specific effects on epileptogenesis in the kindling paradigm. AB - The endocannabinoid system serves as a retrograde negative feedback mechanism. It is thought to control neuronal activity in an epileptic neuronal network. The purpose of this study was to evaluate the impact of the endocannabinoid and endovanilloid systems on both epileptogenesis and ictogenesis. Therefore, we modulated the endocannabinoid and endovanilloid systems genetically and pharmacologically, and analyzed the subsequent impact on seizure progression in the kindling model of temporal lobe epilepsy in mice. In addition, the impact of seizures on associated cellular alterations was evaluated. Our principal results revealed that the endocannabinoid system affects seizure and afterdischarge duration dependent on the neuronal subpopulation being modulated. Genetic deletion of CB1-receptors (CB1Rs) from principal neurons of the forebrain and pharmacological antagonism with rimonabant (5 mg/kg) caused longer seizure duration. Deletion of CB1R from GABAergic forebrain neurons resulted in the opposite effect. Along with these findings, the CB1R density was elevated in animals with repetitively induced seizures. However, neither genetic nor pharmacological interventions had any impact on the development of generalized seizures. Other than CB1, genetic deletion or pharmacological blockade with SB366791 (1 mg/kg) of transient receptor potential vanilloid receptor 1 (TRPV1) had no effect on the duration of behavioral or electrographic seizure activity in the kindling model. In conclusion, we demonstrate that endocannabinoid, but not endovanilloid, signaling affects termination of seizure activity, without influencing seizure severity over time. These effects are dependent on the neuronal subpopulation. Thus, the data argue that the endocannabinoid system plays an active role in seizure termination but does not regulate epileptogenesis. PMID- 25123338 TI - NK-derived IFN-gamma/IL-4 triggers the sexually disparate polarization of macrophages in CVB3-induced myocarditis. AB - Coxsackievirus B3 (CVB3) is a common etiology of myocarditis with an increased morbidity and mortality in males. We previously reported that differential polarization of macrophages contributed to sexually dimorphic susceptibility of mice to CVB3-induced myocarditis. However, the underlying kinetics, impetus as well as the molecular mechanism remain unclear. Here, we demonstrated that myocardial macrophages started to polarize at as early as day 5 post CVB3 infection in both genders of BALB/c mice, with M1 phenotype detected in males and M2a phenotype in females, and this trend was further amplified at day 7 when myocarditis reached peak. In addition, we identified that prevailed IFN-gamma in males and dominant IL-4 in females were critical myocardial cytokines for the disparate macrophage polarization, which respectively activated JAK1-STAT1 and JAK3-STAT6 pathways. Strikingly, we found that the main source of IFN-gamma and IL-4 cytokines in both genders were myocardial infiltrating NK cells, which differentially secreted cytokines in various microenvironments manifested synergistically by sex hormones and CVB3 infection. Consistently, depletion of NK cells significantly impeded the myocardial macrophage polarization in both genders of CVB3-infected mice. Collectively, these data indicated that myocardial NK-derived IFN-gamma/IL-4 was critical for the differential polarization of macrophages in CVB3-induced myocarditis via activating JAK1-STAT1 and JAK3-STAT6 pathways respectively. Our study may help understand the mechanism of sexually differential polarization of macrophages and provide clues for the gender bias in CVB3-induced myocarditis. PMID- 25123339 TI - The link between pediatric heart failure and mitochondrial lipids. PMID- 25123340 TI - Psychometric evaluation of the Marijuana Reduction Strategies Self-Efficacy Scale with young recreational marijuana users. AB - INTRODUCTION: This study evaluated the cue-reactivity and several psychometric properties of a questionnaire designed to assess marijuana users' self-efficacy to employ 21 specific cognitive-behavioral strategies to reduce their marijuana use. METHOD: Using a web-based recruitment and data-collection procedure, 513 regular marijuana users completed dependent measures following marijuana-related or control cue exposure. RESULTS: Although exposure to marijuana-related stimuli significantly increased reported craving, mean reduction-strategy self-efficacy scores did not differ as a function of cue exposure. Reliability analyses supported retaining all 21 items as a single scale. Reduction-strategy self efficacy was positively associated with marijuana-refusal self-efficacy and with recent past use of reduction strategies, was negatively associated with quantity and frequency of marijuana use and marijuana-related problems, and was positively but weakly associated with general self-efficacy. The most frequently reported strategies that were employed reflected restricting marijuana use to once per day, not keeping a large stash available, turning down unwanted hits, and not obtaining more marijuana right away if one's supply runs out. CONCLUSIONS: These findings further support the reliability and validity of the questionnaire when administered to a diverse sample of regular marijuana users. PMID- 25123341 TI - ADHD as a risk factor for early onset and heightened adult problem severity of illicit substance use: an accelerated gateway model. AB - The primary aims of the present study were to assess ADHD history as a risk factor for earlier initiation and current use of licit and illicit substances among a sample of drug using adults. It was hypothesized that ADHD history would accelerate the Gateway Theory of drug use. Participants included 941 drug-using African American and Caucasian individuals in Baltimore, Maryland. The sample consisted of 124 (13.2%) participants who reported a history of ADHD and 817 (86.8%) who reported no history of ADHD. The accelerated gateway hypothesis was supported, as a history of self-reported ADHD was significantly associated with younger ages of initiation for alcohol, cigarettes, marijuana, and cocaine use. Participants with a history of ADHD were also more likely to engage in recent HIV risk behavior, such as injection drug use and needle sharing. This study provides compelling data in support of an accelerated gateway model for substance use related to ADHD history and increased problem severity in adulthood. Targeted substance use prevention and intervention may be beneficial for those with ADHD. PMID- 25123342 TI - It depends on when you ask: motives for using marijuana assessed before versus after a marijuana use event. AB - BACKGROUND: Marijuana use motives are typically evaluated retrospectively using measures that summarize or generalize across episodes of use, which may compromise validity. Using Ecological Momentary Assessment data, we examined the main reason for a specific marijuana use event measured both prospectively and retrospectively. We then determined reason types, event characteristics, and user characteristics that predicted change in reason. METHODS: Thirty-six medical outpatients age 15 to 24 years who used marijuana two times a week or more used a handheld computer to select their main reason for use from the five categories of the Marijuana Motives Measure (Simons, Correia, & Carey, 1998) just before and after each time they used marijuana over two weeks (n=263 events with before/after reason). The reasons were examined individually and according to dimensions identified in motivational models of substance use (positive/negative, internal/external). RESULTS: The reason assessed before use changed to a different reason after use for 20% of events: 10% of events for pleasure; 21%, to cope; 35%, to be more social; 55%, to expand my mind; and 100%, to conform. In the multivariable model, external and expansion reasons each predicted change in reason for use (p<0.0001 and p=0.001, respectively). Youth were also more likely to change their reason if older (p=0.04), if male (p=0.02), and with weekend use (p=0.002). CONCLUSION: Retrospective assessments of event-specific motives for marijuana use may be unreliable and therefore invalid for a substantial minority of events, particularly if use is for external or expansion reasons. PMID- 25123343 TI - Cannabis use and suicidal ideations in high-school students. AB - BACKGROUND: The association of cannabis use and suicidal ideations in adolescents has been inconsistent. This discrepancy may reflect differences in controlled confounders. In particular, no study has controlled for personality disorder traits linked to both cannabis use and suicidality such as borderline and psychopathic personality traits. METHOD: Participants were 972 high-school students who completed questionnaires assessing cannabis use, suicidal ideations, depressive symptoms, social anxiety symptoms, and borderline and psychopathic personality traits. RESULTS: Cannabis use was not a significant independent predictor of suicidal ideations after adjustment for confounding personality traits in the total sample and in the subsample of cannabis users. PMID- 25123344 TI - Differences in quit attempts between non-Hispanic Black and White daily smokers: the role of smoking motives. AB - INTRODUCTION: The prevalence of smoking across racial/ethnic groups has declined over the years, yet racial health disparities for smoking persist. Studies indicate that non-Hispanic Black smokers attempt to quit smoking more often compared to non-Hispanic White smokers but are less successful at doing so. Research suggests that motives to quit smoking differ by race, however, less is known about the role of motives to smoke in explaining racial differences in attempts to quit smoking. METHODS: This study examined whether smoking motives accounted for the differential rates in quit attempts between non-Hispanic Black (n=155) and non-Hispanic White (n=159) smokers. Data were culled from a larger study of heavy-drinking smokers. The Wisconsin Index of Smoking Dependence Motives (WISDM) assessed motives to smoke. RESULTS: As expected, Black and White smokers reported similar smoking patterns, yet Black smokers reported higher rates of failed attempts to quit smoking than White smokers. Findings indicated that Black, compared to White, smokers endorsed lower scores in the negative reinforcement, positive reinforcement, and taste WISDM subscales and scores in these subscales mediated the relationship between race and quit attempts. CONCLUSIONS: In this study, Blacks, compared to Whites, endorsed lower motives to smoke, which are generally associated with successful quit attempts, yet they experienced more failed attempts to quit smoking. This study demonstrates racial health disparities at the level of smoking motives and suggests that Black smokers remain vulnerable to failed quit attempts despite reporting lower motives to smoke. PMID- 25123345 TI - Violent offending severity among injecting drug users: examining risk factors and issues around classification. AB - OBJECTIVE: There is a paucity of research as to how injecting drug users (IDU) might be differentiated in the severity of their violent offending. This paper reported on the risks associated with severity, as well as issues around severity classification and the impact on observed relationships with known major risk factors. METHOD: A cross-sectional survey administered to 300 IDU, who had injected drugs weekly or more in the past 12months. A structured questionnaire addresses potential substance use and early-life risk factors for violent offending. RESULTS: Four severity groups were identified: non-violent (24%), low (34%), moderate (22%) and high (20%) level offenders. Higher severity groups had more prevalent and more severe histories of childhood maltreatment, child psychopathology and dysfunctional trait personalities, as well as more severe substance use problems than low-level and non-violent IDU. Regression analyses found that only two of 15 risk factors remained uniformly associated with violent offending across the four classification schemes tested: (1) having committed violence under the influence and (2) having more impulsive trait personalities. CONCLUSIONS: Disaggregating IDU into distinct subgroups showed that the extent and severity of predispositional and substance use risk exposure corresponded to the severity of violent offending. There is a need to establish a systematic method for classifying severity given that there were clinically meaningful differences between groups which require further exploration and replication, and because there was extensive variation in the risks associated with severity across schemes. PMID- 25123346 TI - Typology of driving-under-the-influence (DUI) offenders revisited: Inclusion of DUI-specific attitudes. AB - OBJECTIVES: Much work remains to improve rehabilitative interventions for driving under-the-influence (DUI) offenders. There is heterogeneity of patterns of alcohol use, personality, and driving behaviour within DUI offenders, but little is known about how their appraisal of DUI differs. This study investigated within offender variability in DUI-specific attitudinal variables. METHOD: Convicted male DUI offenders (N=219) living in greater Tokyo were interviewed. Cluster analysis was undertaken using age, psychological distress, personality trait, alcohol use, and attitudes towards DUI. Discriminant function analysis explored the relative explanatory power of the grouping variables. RESULT: Many offenders reported current excessive alcohol consumption. About 26-36% of the participants were potentially alcohol-dependent based on screening instruments/biomarkers. Cluster analysis identified five subgroups. The biggest subgroup considered their DUI a singular mistake and reported strong self-efficacy for avoiding further DUI (clusters 1 and 2). A small subgroup manifested alcohol dependence, psychological distress, higher impulsivity, and lower self-efficacy for avoiding DUI (cluster 3). Another subgroup exhibited a tendency to rationalise DUI, higher likelihood of future DUI, and lower self-efficacy for avoiding DUI (cluster 4). Most participants in another small subgroup abstained from alcohol use temporarily after their convictions (cluster 5). CONCLUSION: The majority of DUI offenders regarded their DUI conviction as an exceptional mishap, while they continued consuming hazardous amounts of alcohol. DUI-specific attitudinal variables, including DUI rationalisation and self-efficacy for avoiding future DUI incidents, constituted a distinct aspect of the problem, suggesting the need to address this issue in addition to the underlying alcohol use problem. PMID- 25123347 TI - Comparing college smokers' and dual users' expectancies towards cigarette smoking. AB - BACKGROUND: As no agreed upon definition exists for dual use (i.e., individuals who concurrently use more than one form of tobacco), this population remains largely unstudied in the substance use literature, despite increases in smokeless tobacco use among young adults. Individuals 18-25years of age report the highest rates of smokeless tobacco use, dual use, and cigarette use. The current study compared the smoking outcome expectancies of college student dual users to those who reported only smoking cigarettes. METHODS: The Short Form of the Smoking Consequences Questionnaire was used to examine potential differences in positive or negative expectations regarding cigarette use. RESULTS: Data from this study suggest that smokers believe that smoking will lead to greater positive consequences ("cigarettes taste good"), negative reinforcement ("cigarettes help me deal with anger"), and weight/appetite reduction ("smoking controls my appetite") when compared to dual users. Conversely, dual users believed that smoking would lead to greater negative consequences (e.g., "smoking is taking years off of my life"). DISCUSSION: These results may help to explain why some smokers choose not to use smokeless tobacco products for harm reduction or smoking cessation purposes, as well as why increases are being observed in smokeless tobacco rates among young adults. PMID- 25123348 TI - Neurobiological correlates of physical self-concept and self-identification with avatars in addicted players of Massively Multiplayer Online Role-Playing Games (MMORPGs). AB - AIMS: MMORPG addiction has been associated with self-concept impairments and increased identification with the own avatar. Yet, the underlying neurobiological mechanisms of self-identification with avatars, especially reflected in the left angular gyrus (AG), have only been assessed in regular gamers. Therefore, the study aims to examine neurobiological processes in addicted MMORPG players while evaluating their own and their personal avatar's body image (physical self concept). METHODS: Sixteen addicted and seventeen non-addicted gamers underwent functional Magnetic Resonance Imaging (fMRI) while viewing images of themselves, their own avatar and unfamiliar persons. The Body Image Questionnaire (FKB-20) and Visual Analog Scales (VAS) assessing the degree of attractiveness, sympathy and gender identity of the self, of the avatar as well as of the unfamiliar persons were applied. RESULTS: Addicts showed a significantly extended negative body image and lower gender identity levels as well as decreased bilateral brain activations in the AG and the middle occipital gyrus during self-perception. They further exhibited higher activations in the left AG during avatar-perception. Regression analyses in the overall group and in addicted gamers indicated a significant positive correlation between gender identity and brain activation in the left AG during self-perception. CONCLUSIONS: Our results confirm addicted MMORPG players to have physical self-concept deficits which may be related to hypoactivations in the AG. The findings further indicate addicted gamers to have a tendency to identify themselves easier with their own avatar than with their real self. Lower gender identity levels might be associated with physical self concept deficits in MMORPG addiction. PMID- 25123349 TI - Alcohol use, impulsivity, and the non-medical use of prescription stimulants among college students. AB - The non-medical use of prescription drugs (NMUPD) is a growing public health concern. College students have been identified as a particularly at risk population for engagement in NMUPD. Across all prescription drug classes, stimulants show the highest ratio of illicit to medical use and are thus important to examine within this population. Emerging research has suggested a relationship between the non-medical use of prescription stimulants (NMUPS) and alcohol use within the college student population. Finally, the construct of impulsivity may serve as an additional indicator for students who engage in NMUPS as well as those who engage in NMUPS/alcohol co-ingestion. The purpose of this paper is to expand on previous prevalence data collected for the past year NMUPS and NMUPS/alcohol co-ingestion. Additionally, this paper examines whether those who engage in NMUPS or NMUPS/alcohol co-ingestion differ significantly from their non-using counterparts on measures of alcohol use, alcohol related negative consequences, binge drinking, and impulsivity. Finally, binary logistic regression models indicated that increased alcohol use, alcohol related negative consequences, and impulsivity all significantly increase the odds of an individual engaging in NMUPS or NMUPS/alcohol co-ingestion. PMID- 25123350 TI - From hundreds to thousands: Widening the normal human Urinome (1). AB - It is currently unknown how many proteins can be detected in urine. Improving the analytical approach would increase their number and potentially strengthen their predictive potential in diseases. We developed a combination of analytical procedures for maximizing sensitivity and reproducibility of normal human urinary proteome analysis based on ultracentrifugation, vesicles separation, combinatorial peptide ligand libraries (CPLL) and solvent removal of pigments. Proteins were identified by an Orbitrap Velos Mass Spectrometry. Overall, 3429 proteins were characterized: most components (1615) were contained in vesicles while the remaining 1794 were equally distributed among CPLL and butanol insoluble fractions. Several proteins were detected exclusively in one of the phases of the procedure, suggesting that each step is crucial in the fractionation strategy. Many (1724) proteins are described here whose presence in urine has never been reported and represents a potential source of information considering that urine is the unique site of excretion of products of interaction of metabolic processes. Improving the characterization of normal urinary proteome would also represent the basis for the analysis of urine biomarkers in human diseases. BIOLOGICAL SIGNIFICANCE: Sub-fractionating normal urine by successive steps (vesicle separation, CPLL and solvent treatments) allowed the identification of 3429 proteins, a relevant part (1724) being detected for the first time in urine. Several proteins of new description have been implicated in physiology pathways and in pathologies thus representing a potential source of new information on both metabolic processes and diseases. PMID- 25123351 TI - Extended bottom-up proteomics with secreted aspartic protease Sap9. AB - We investigate the benefits and experimental feasibility of approaches enabling the shift from short (1.7 kDa on average) peptides in bottom-up proteomics to about twice longer (~3.2 kDa on average) peptides in the so-called extended bottom-up proteomics. Candida albicans secreted aspartic protease Sap9 has been selected for evaluation as an extended bottom-up proteomic-grade enzyme due to its suggested dibasic cleavage specificity and ease of production. We report the extensive characterization of Sap9 specificity and selectivity revealing that protein cleavage by Sap9 most often occurs in the vicinity of proximal basic amino acids, and in select cases also at basic and hydrophobic residues. Sap9 is found to cleave a large variety of proteins in a relatively short, ~1 h, period of time and it is efficient in a broad pH range, including slightly acidic, e. g., pH5.5, conditions. Importantly, the resulting peptide mixtures contain representative peptides primarily in the target 3-7 kDa range. The utility and advantages of this enzyme in routine analysis of protein mixtures are demonstrated and the limitations are discussed. Overall, Sap9 has a potential to become an enzyme of choice in an extended bottom-up proteomics, which is technically ready to complement the traditional bottom-up proteomics for improved targeted protein structural analysis and expanded proteome coverage. BIOLOGICAL SIGNIFICANCE: Advances in biological applications of mass spectrometry-based bottom-up proteomics are oftentimes limited by the extreme complexity of biological samples, e.g., proteomes or protein complexes. One of the reasons for it is in the complexity of the mixtures of enzymatically (most often using trypsin) produced short (<3 kDa) peptides, which may exceed the analytical capabilities of liquid chromatography and mass spectrometry. Information on localization of protein modifications may also be affected by the small size of typically produced peptides. On the other hand, advances in high-resolution mass spectrometry and liquid chromatography have created an intriguing opportunity of improving proteome analysis by gradually increasing the size of enzymatically derived peptides in MS-based bottom-up proteomics. Bioinformatics has already confirmed the envisioned advantages of such approach. The remaining bottle-neck is an enzyme that could produce longer peptides. Here, we report on the characterization of a possible candidate enzyme, Sap9, which may be considered for producing longer, e.g., 3-7 kDa, peptides and lead to a development of extended bottom-up proteomics. PMID- 25123352 TI - Caries-preventive effectiveness of fluoride varnish as adjunct to oral health promotion and supervised tooth brushing in preschool children: a double-blind randomized controlled trial. AB - OBJECTIVES: To evaluate the effect of biannual fluoride varnish applications in preschool children as an adjunct to school-based oral health promotion and supervised tooth brushing with 1000ppm fluoride toothpaste. METHODS: 424 preschool children, 2-5 year of age, from 10 different pre schools in Athens were invited to this double-blind randomized controlled trial and 328 children completed the 2-year programme. All children received oral health education with hygiene instructions twice yearly and attended supervised tooth brushing once daily. The test group was treated with fluoride varnish (0.9% diflurosilane) biannually while the control group had placebo applications. The primary endpoints were caries prevalence and increment; secondary outcomes were gingival health, mutans streptococci growth and salivary buffer capacity. RESULTS: The groups were balanced at baseline and no significant differences in caries prevalence or increment were displayed between the groups after 1 and 2 years, respectively. There was a reduced number of new pre-cavitated enamel lesions during the second year of the study (p=0.05) but the decrease was not statistically significant. The secondary endpoints were unaffected by the varnish treatments. CONCLUSIONS: Under the present conditions, biannual fluoride varnish applications in preschool children did not show significant caries-preventive benefits when provided as an adjunct to school-based supervised tooth brushing with 1000ppm fluoride toothpaste. CLINICAL SIGNIFICANCE: In community based, caries prevention programmes, for high caries risk preschool children, a fluoride varnish may add little to caries prevention, when 1000ppm fluoride toothpaste is used daily. PMID- 25123353 TI - ASC, a bioactive steroidal saponin from Ophitopogin japonicas, inhibits angiogenesis through interruption of Src tyrosine kinase-dependent matrix metalloproteinase pathway. AB - As angiogenesis is an important target for antitumour drugs, the agents that inhibit angiogenesis may help reduce the use of chemotherapy by blocking tumour blood supply. In this study, we investigated a potent angiogenesis inhibitor, ASC, a steroidal saponin compound, which has been purified from Ophitopogin japonicus (L.f) Ker.-Gawl. Our observations showed that ASC significantly suppressed human umbilical vein endothelial cell (HUVECs) growth both in vitro and in vivo. This may be resulted from the G2/M cell cycle arrest effects of ASC. Moreover, ASC inhibited HUVECs invasion and tube formation processes, which were associated with endothelial cells remodelling. A mechanism study indicated that ASC down-regulated the expression of Src tyrosine kinase, further leading to the blockage of Akt-dependent matrix metalloproteinases (mainly for MMP-9) signalling pathway, which was functionally associated with angiogenic blood vessels. Finally, ASC significantly inhibited angiogenesis and MMPs/VEGF expression in the subcutaneously injected matrigel in C57/BL mice. These findings suggest that ASC might be a potential drug candidate in anti-angiogenesis and anticancer therapies. PMID- 25123354 TI - The influence of eating disorders on mothers' sensitivity and adaptation during feeding: a longitudinal observational study. AB - BACKGROUND: Parents with past and current eating disorders (ED) have been shown to report troubles nourishing their infants. This could increase the risk of infant feeding problems linked to maternal anxiety and depression. It is not clear how mothers' eating difficulties before pregnancy and at the time of birth can affect infant's feeding. We aimed to specify the impact of eating disorders on mothers' adaptation and sensitivity to their offspring during feeding, by comparing a population of mothers with eating disorders and controls. METHODS: Twenty-eight women agreed to participate in interviews and filmed mother-baby interactions. Pregnant women consulting at an obstetric unit for care follow-up were screened and tested for symptoms of eating disorders with the EDE-Q Questionnaire (Eating Disorders Examination Questionnaire) and the EDE Interview (Eating Disorders Examination Interview). Infant functional troubles and mothers' sensitivity were investigated through the Symptom Check List. Reciprocal adaptation during feeding with their new-borns was filmed and analysed with the Chatoor Infant Feeding Scale. Before pregnancy, two women suffered from anorexia, three suffered from bulimia, three had binge eating symptoms and two were diagnosed with EDNOS (Eating Disorders Not Otherwise Specified). RESULTS: Mothers suffering from ED tended to show more difficult interactive patterns in terms of dyadic reciprocity when feeding their babies compared with mothers with no symptoms of eating disorders. In the interviews, other than the behavioural data gathered, ED mothers expressed feeling more dissatisfaction and uneasiness during feeding. CONCLUSIONS: Pregnancy seems to be an useful period for interviewing women on eating disorders, allowing for the design and implementation of prevention programmes based on mothers' narratives and infant/mother observations and treatment. PMID- 25123355 TI - Intracolonial genetic variation affects reproductive skew and colony productivity during colony foundation in a parthenogenetic termite. AB - BACKGROUND: In insect societies, intracolonial genetic variation is predicted to affect both colony efficiency and reproductive skew. However, because the effects of genetic variation on these two colony characteristics have been tested independently, it remains unclear whether they are affected by genetic variation independently or in a related manner. Here we test the effect of genetic variation on colony efficiency and reproductive skew in a rhinotermitid termite, Reticulitermes speratus, a species in which female-female pairs can facultatively found colonies. We established colonies using two types of female-female pairs: colonies founded by sisters (i.e., sister-pair colonies) and those founded by females from different colonies (i.e., unrelated-pair colonies). Colony growth and reproductive skew were then compared between the two types of incipient colonies. RESULTS: At 15 months after colony foundation, unrelated-pair colonies were larger than sister-pair colonies, although the caste ratio between workers and nymphs, which were alternatively differentiated from young larvae, did not differ significantly. Microsatellite DNA analyses of both founders and their parthenogenetically produced offspring indicated that, in both sister-pair and unrelated-pair colonies, there was no significant skew in the production of eggs, larvae, workers and soldiers. Nymph production, however, was significantly more skewed in the sister-pair colonies than in unrelated-pair colonies. Because nymphs can develop into winged adults (alates) or nymphoid reproductives, they have a higher chance of direct reproduction than workers in this species. CONCLUSIONS: Our results support the idea that higher genetic variation among colony members could provide an increase in colony productivity, as shown in hymenopteran social insects. Moreover, this study suggests that low genetic variation (high relatedness) between founding females increases reproductive skew via one female preferentially channeling her relatives along the reproductive track. This study thus demonstrated that, in social insects, intracolonial genetic variation can simultaneously affect both colony efficiency and reproductive skew. PMID- 25123356 TI - Self-adhesive epidermal carbon nanotube electronics for tether-free long-term continuous recording of biosignals. AB - The long-term, continuous, inconspicuous, and noiseless monitoring of bioelectrical signals is critical to the early diagnosis of disease and monitoring health and wellbeing. However, it is a major challenge to record the bioelectrical signals of patients going about their daily lives because of the difficulties of integrating skin-like conducting materials, the measuring system, and medical technologies in a single platform. In this study, we developed a thin epidermis-like electronics that is capable of repeated self-adhesion onto skin, integration with commercial electronic components through soldering, and conformal contact without serious motion artifacts. Using well-mixed carbon nanotubes and adhesive polydimethylsiloxane, we fabricated an epidermal carbon nanotube electronics which maintains excellent conformal contact even within wrinkles in skin, and can be used to record electrocardiogram signals robustly. The electrode is biocompatible and can even be operated in water, which means patients can live normal lives despite wearing a complicated recording system. PMID- 25123358 TI - Unilateral ear and temporomandibular joint discomfort. PMID- 25123357 TI - Re-irradiation of recurrent glioblastoma multiforme using 11C-methionine PET/CT/MRI image fusion for hypofractionated stereotactic radiotherapy by intensity modulated radiation therapy. AB - BACKGROUND: This research paper presents a valid treatment strategy for recurrent glioblastoma multiforme (GBM) using hypofractionated stereotactic radiotherapy by intensity modulated radiation therapy (HS-IMRT) planned with 11C-methionine positron emission tomography (MET-PET)/computed tomography (CT)/magnetic resonance imaging (MRI) fusion. METHODS: Twenty-one patients with recurrent GBM received HS-IMRT planned by MET-PET/CT/MRI. The region of increased amino acid tracer uptake on MET-PET was defined as the gross tumor volume (GTV). The planning target volume encompassed the GTV by a 3-mm margin. Treatment was performed with a total dose of 25- to 35-Gy, given as 5- to 7-Gy daily for 5 days. RESULTS: With a median follow-up of 12 months, median overall survival time (OS) was 11 months from the start of HS-IMRT, with a 6-month and 1-year survival rate of 71.4% and 38.1%, respectively. Karnofsky performance status was a significant prognostic factor of OS as tested by univariate and multivariate analysis. Re-operation rate was 4.8% for radiation necrosis. No other acute or late toxicity Grade 3 or higher was observed. CONCLUSIONS: This is the first prospective study of biologic imaging optimized HS-IMRT in recurrent GBM. HS-IMRT with PET data seems to be well tolerated and resulted in a median survival time of 11 months after HS-IMRT. PMID- 25123359 TI - Reduction in C-terminal amidated species of recombinant monoclonal antibodies by genetic modification of CHO cells. AB - BACKGROUND: During development of recombinant monoclonal antibodies in Chinese hamster ovary (CHO) cells, C-terminal amidated species are observed. C-terminal amidation is catalysed by peptidylglycine alpha-amidating monooxygenase (PAM), an enzyme known to be expressed in CHO cells. The significant variations between clones during clone selection, and the relatively high content of amidated species (up to 15%) in comparison to reference material (4%), led us to develop a cell line with reduced production of C-terminal amidated monoclonal antibodies using genetic manipulation. RESULTS: Initial target validation was performed using the RNA interference approach against PAM, which resulted in a CHO cell line with C-terminal amidation decreased to 3%. Due to the transient effects of small-interfering RNAs, and possible stability problems using short-hairpin RNAs, we knocked-down the PAM gene using zinc finger nucleases. Plasmid DNA and mRNA for zinc finger nucleases were used to generate a PAM knock-out, which resulted in two CHO cell lines with C-terminal amidation decreased to 6%, in CHO Der2 and CHO Der3 cells. CONCLUSION: Two genetically modified cell lines were generated using a zinc finger nuclease approach to decrease C-terminal amidation on recombinant monoclonal antibodies. These two cell lines now represent a pool from which the candidate clone with the highest comparability to the reference molecule can be selected, for production of high-quality and safe therapeutics. PMID- 25123360 TI - Understanding the experience of myotonic dystrophy. Mixed method study. AB - Myotonic dystrophy (DM) is a progressive multi-systemic disorder characterized by myotonia and muscle weakness where currently no effective treatment or cure to prevent or delay the disorder exists. This study used mixed methods to examine the experience of living with DM, in patients and their close relatives. Thirteen patients and eight next of kin responded completing Quality of Life and Psychological distress questionnaires in this cross-sectional study, and participating in a semi-structured interview. The findings indicate a higher level of anxiety and hopelessness in next of kin compared to patients, while patients were more depressed. Next of kin reported higher physical, but lower emotional quality of life than patients. Qualitative interviews confirmed the questionnaire findings. The findings from this study may be helpful in genetic counseling. Genetic counselors and geneticists should not only be aware of the burden of being a next of kin, but include discussions about opportunities to minimize the burden in families affected with DM. The findings may be of relevance in counseling for other types of neuromuscular disorders. PMID- 25123362 TI - Enhanced bioconversion of ethylene glycol to glycolic acid by a newly isolated Burkholderia sp. EG13. AB - Burkholderia sp. EG13 with high ethylene glycol-oxidizing activity was isolated from soil, which could be used for the synthesis of glycolic acid from the oxidation of ethylene glycol. Using the resting cells of Burkholderia sp. EG13 as biocatalysts, the optimum reaction temperature and pH were 30 degrees C and 6.0, respectively. After 24 h of biotransformation, the yield of glycolic acid from 200 mM ethylene glycol was 98.8 %. Furthermore, an integrated bioprocess for the production of glycolic acid which involved in situ product removal (ISPR) was investigated. Using fed-batch method with ISPR, a total of 793 mM glycolic acid has been accumulated in the reaction mixture after the 4th feed. PMID- 25123361 TI - Tracing the emergence of multidrug-resistant Acinetobacter baumannii in a Taiwanese hospital by evaluating the presence of integron gene intI1. AB - BACKGROUND: In Changhua County, Taiwan, the number of clinical Acinetobacter baumannii isolates has risen since 2002, and multidrug-resistant Acinetobacter baumannii (MDRAB) has spread rapidly throughout Taiwan. In this study, to reveal the mechanism involved with the rapid dissemination of MDRAB emergence, the utility of the class 1 integron, intI1 integrase gene, as an MDRAB-associated biomarker was examined. A cross-sectional, clinical epidemiological study was performed at Changhua Christian Hospital between January 1st, 2001 and December 31st, 2004. Besides the existence of intI1 gene was examined, the pulse-field gel electrophoresis (PFGE) was also performed to determine the epidemiological characteristics of the isolates. FINDINGS: The overall hospital infection rate was 5-6%, while the infection rate of the intensive care unit (ICU) fluctuated. No positive correlation was observed between MDRAB isolates and the presence of intI1 (r = 0.168, P = 0.254). Additionally, no positive correlation was observed between the infection rate in the ICU and the presence of intI1 (r = -0.107, P = 0.468) or between the hospital infection rate and the presence of intI1 (r = 0.189, P = 0.199). However, two predominant clones among the MDRAB isolates were identified by PFGE. CONCLUSIONS: Although the presence of the intI1 gene does not seem suitable for tracing MDRAB emergence in Changhua County, two predominant clones were identified by PFGE, and subsequent studies to identify whether these clones were responsible for original nosocomial infection are needed. PMID- 25123363 TI - High overexpression and purification of optimized bacterio-opsin from Halobacterium Salinarum R1 in E. coli. AB - The purple membrane of Halobacterium Salinarum carries out a protein, bacteriorhodopsin (bR), which is a model for structure-function studies of membrane proteins. The heterologous expression of integral membrane proteins (IMPS) is difficult. In this study, we reported the heterologous overexpression of bacterio-opsin (bO) in Escherichia coli BL21 (DE3). Bacterio-opsin expression is facilitated by using mistic, a membrane protein from Bacillus subtilis in E. coli BL21 (DE3) membranes. The optimized bO gene was cloned in fusion to the C terminus of mistic in pET 30a (+) and contains an oct-histidine in C-terminal to facilitate purification. Different medium, temperature, and induction time were used to optimize protein overexpression. The highest expression was obtained from the Terrific Broth (TB) medium at 18 degrees C with an IPTG concentration of 0.1 mM. The final purified bR was 192 +/- 1 mg/L which has an important value for the production of membrane proteins in E. coli. PMID- 25123364 TI - Improved pretreatment process using an electron beam for optimization of glucose yield with high selectivity. AB - In this study, electron beam irradiation (EBI) assisted by a dilute acid pretreatment process was investigated to improve the glucose yield and show high selectivity in the enzymatic hydrolysis of rice straw. In the first step, EBI of rice straw was performed at various doses ranging from 50 to 500 kGy. The electron beam-irradiated rice straw was then autoclaved with 3 % dilute acid at 120 degrees C for 1 h. The pretreated rice straw was finally subjected to enzymatic hydrolysis at 50 degrees C for 24, 48, and 72 h by 70 filter paper units (FPU)/mL cellulase and 40 cellobiose units (CbU)/mL glucosidase. Glucose was obtained with a very high selectivity of 92.7 % and a total sugar yield of 80 % from pretreated rice straw after 72 h of enzymatic hydrolysis. PMID- 25123365 TI - Temperature Dependence of the Complexation Mechanism of Celecoxib and Hydroxyl beta-cyclodextrin in Aqueous Solution. AB - Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is commonly used as a complexation reagent to solubilize compounds with poor aqueous solubility to improve in vivo dosing. However, the degree of solubility enhancement was often limited by the formation of only a 1:1 complex and a low complexation constant (K). Such a limitation can be significantly improved by the formation of 1:2 complexes in some cases. Despite the understanding of the solubility advantage of the formation of the 1:2 complexes, there is no systematic understanding that could drive for the formation of 1:2 complexes. Thus, in most cases, the formation of 1:2 complexes was limited by observation bases. In this study, we pioneer the usages of molecular dynamics (MD) simulation to understand the phenomena of a model drug of celecoxib (CCB) and HP-beta-CD. It has been reported that celecoxib (CCB) forms 1:1 complexes with cyclodextrin in solution; however, some data suggest the existence of a 1:2 complex. The simulation results suggest that a transition state of CCB and HP-beta-CD may exit at a higher temperature of CCB and HP-beta-CD; a model drug, such as celecoxib (CCB), that is known to form 1:1 complexes can achieve a higher degree of complexation (1:2) and obtain much improved solubility when the same amount of cyclodextrin was used and demonstrated in vitro. The simulation results of CCB and HP-beta-CD could be a model system that may provide important insights into the inclusion mechanism. PMID- 25123367 TI - [Hereditary transthyretin amyloidosis]. AB - Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused by extracellular deposition of misfolded proteins and, therefore represents a hereditary protein folding or deposition disease that leads to progressive organ damage and eventually death. In most instances mutations within the transthyretin gene are the underlying cause. The main manifestation is a rapidly progressing axonal sensorimotor and autonomic polyneuropathy (familial amyloid polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional manifestations include the gastrointestinal tract and the eyes. A second manifestation type is cardiomyopathy with little or no polyneuropathy (familial amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has been established for 25 years. Recently, the oral agent tafamidis, a transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy. Additional treatment options are currently being studied. PMID- 25123368 TI - [Spirituality in schizophrenic diseases]. AB - OBJECTIVE: The aim of this study was to investigate different dimensions of religiosity and spirituality among schizophrenic inpatients (F 2x) compared to addiction patients (F 10.2, F 19.2) and to healthy controls. In addition the dimensions of religious and spiritual well-being were examined and related to different parameters of mental illness. METHOD: The group of schizophrenic patients (n = 39) was compared to a group of addiction patients (n = 33) and a healthy control group (n = 38) by means of the multidimensional inventory for religious/spiritual well-being (MI-RSWB). Additionally, dimensions of RSWB were related to the Beck depression inventory (BDI) and the brief symptom inventory (BSI) in the group of schizophrenic patients. RESULTS: The group of schizophrenic patients did not differ from the addiction patients or from the healthy controls in the RSWB dimensions, except for the hope transcendent sub-dimension. Furthermore, dimensions of RSWB turned out to be negatively correlated with the severity of psychiatric symptoms (BDI and BSI). CONCLUSION: As assumed a positive relationship between RSWB and subjective well-being can be confirmed also for the group of schizophrenic patients. Existentially oriented dimensions such as hope and forgiveness might be specifically relevant for the group of schizophrenics. PMID- 25123366 TI - [Neurobiology of schizophrenia: new findings from the structure to the molecules]. AB - During recent years improved methods in neuroimaging, molecular biology and genetics contributed to new insights into the neurobiology of schizophrenia. This review summarizes and discusses current findings and their impact on the pathophysiology of the disease. New magnetic resonance imaging (MRI) based methods allow investigation of small subregions of the hippocampus and structural and functional connectivity analyses using multimodal imaging approaches. Volume deficits are correlated with MRI spectroscopy based data of the glutamatergic and GABAergic systems and confirm the glutamate hypothesis of schizophrenia. Due to detailed clinical investigations, the association between brain imaging, symptom dimensions and cognitive deficits are becoming more evident. Genome-wide microarray assessments facilitate more detailed analyses of groups of differentially expressed genes and will advance with the application of next generation sequencing (NGS) and the development of inducible pluripotent stem cells. To date a multitude of new risk genes have been detected due to genome wide association studies, each with a small effect. Future challenges encompass the identification of their neurobiological function and impact on neuroplastic processes, brain structure and function. Based on such information, the development of innovative risk-based therapy strategies is to be expected. PMID- 25123369 TI - Model selection in historical biogeography reveals that founder-event speciation is a crucial process in Island Clades. AB - Founder-event speciation, where a rare jump dispersal event founds a new genetically isolated lineage, has long been considered crucial by many historical biogeographers, but its importance is disputed within the vicariance school. Probabilistic modeling of geographic range evolution creates the potential to test different biogeographical models against data using standard statistical model choice procedures, as long as multiple models are available. I re-implement the Dispersal-Extinction-Cladogenesis (DEC) model of LAGRANGE in the R package BioGeoBEARS, and modify it to create a new model, DEC + J, which adds founder event speciation, the importance of which is governed by a new free parameter, [Formula: see text]. The identifiability of DEC and DEC + J is tested on data sets simulated under a wide range of macroevolutionary models where geography evolves jointly with lineage birth/death events. The results confirm that DEC and DEC + J are identifiable even though these models ignore the fact that molecular phylogenies are missing many cladogenesis and extinction events. The simulations also indicate that DEC will have substantially increased errors in ancestral range estimation and parameter inference when the true model includes + J. DEC and DEC + J are compared on 13 empirical data sets drawn from studies of island clades. Likelihood-ratio tests indicate that all clades reject DEC, and AICc model weights show large to overwhelming support for DEC + J, for the first time verifying the importance of founder-event speciation in island clades via statistical model choice. Under DEC + J, ancestral nodes are usually estimated to have ranges occupying only one island, rather than the widespread ancestors often favored by DEC. These results indicate that the assumptions of historical biogeography models can have large impacts on inference and require testing and comparison with statistical methods. PMID- 25123371 TI - Distal bypasses in patients with diabetes and infrapopliteal disease: technical considerations to achieve success. AB - The combination of diabetes and peripheral arterial disease (PAD) is challenging in many ways. The characteristic and complex distal distribution of PAD often encountered in patients with diabetes means that bypass surgery in this context is technically challenging. In addition, many of these patients have a burden of serious comorbidities that must be optimized and managed concurrently. While the authors acknowledge that "achieving success" in distal bypass relies on much more than technical expertise, there are some technical aspects that should be considered when planning surgery on these patients. This article outlines some important issues in the treatment pathway of a patient with diabetes and PAD requiring distal bypass surgery--from selection and optimization of the patient (in the context of a multidisciplinary team) and preoperative workup, to the operative strategy planning, technical tips, and nonoperative adjuncts. These considerations, as well as sound knowledge of the underlying disease process, confounding medical factors and awareness of the difficulty in predicting treatment outcomes, should help maximize the chances of success. PMID- 25123372 TI - Do you want to organize a multidisciplinary diabetic foot clinic? We can help. AB - The diabetic foot (DF) is a complex pathology involving the lower limb of 8 to 10 million people around the world, and its prevalence is rising, creating a dramatic need for effective therapeutic answers. The multidisciplinary DF clinic has been proposed as a model to fight this complication from the International Working Group on Diabetic Foot (IWGDF) inside a more articulated 3-level organization strategy. The organization and technical aspects of this strategy, together with the characteristics of each of the 3 levels have been analyzed and described in the article, together with the aims and limitations of each of the levels to cope with a 3-dimensional pathology involving systemic, local, and logistic aspects. The implementation of this model in Europe produced positive results measured so far in at least 2 nationwide experiences, in Germany and in Italy, and it should be taken in account whenever health policies apply to the DF issue. PMID- 25123370 TI - The cereal starch endosperm development and its relationship with other endosperm tissues and embryo. AB - The cereal starch endosperm is the central part of endosperm, and it is rich in starch and protein which are the important resources for human food. The starch and protein are separately accumulated in starch granules and protein bodies. Content and configuration of starch granules and protein bodies affect the quality of the starch endosperm. The development of starch endosperm is mediated by genes, enzymes, and hormones, and it also has a close relationship with other endosperm tissues and embryo. This paper reviews the latest investigations on the starch endosperm and will provide some useful information for the future researches on the development of cereal endosperm. PMID- 25123373 TI - Confronting a dramatic situation: the charcot foot complicated by osteomyelitis. AB - Charcot osteoarthropathy is a serious complication of diabetic neuropathy. Its prevalence in the diabetic population varies in the literature in relation to certain variables, such as the method of assessment, clinical or instrumental; the population studied; and the scope of the selection. This article is intended as a review of the recent literature concerning Charcot osteoarthropathy in its evolution and complications characterized by the development of ulceration and subsequent bone infection. Diagnosis and treatment strategies--either medical or surgical--are discussed both for Charcot arthropathy and osteomyelitis. PMID- 25123374 TI - Atraumatic intubation: experience using a 5.0 endotracheal tube without a stylet for laryngeal surgery. AB - OBJECTIVES/HYPOTHESIS: Vocal fold injury is a well-know complication of intubation, with rates reported as high as 69%. Laryngology textbooks recommend the use of a small endotracheal tube (ETT) to help avoid these complications and optimize visualization. Case reports have suggested that the rigid stylet can lead to laryngeal injury. Given the additional risks, intubation without the stylet is our preferred practice. There is limited documentation in the literature regarding this viewpoint. Our study investigated the feasibility of and potential barriers to intubation using 5.0 ETT without a stylet. STUDY DESIGN: Prospective study. METHODS: Consecutive adult patients undergoing laryngeal surgery were recruited for intubation with a 5.0 ETT without a stylet. Demographic data, specialty and training level of the intubator, and factors that would predict a difficult intubation were recorded. Descriptive statistical analysis was performed. RESULTS: Findings of the participants (n = 67) included average American Society of Anesthesiologists (ASA) physical status classification (2.2), average Mallampati score (1.7), average Cormack-Lehane grade (1.5), and average body mass index (28.0). Five patients (7.4%) required intubation using a stylet, and one of these five participants was intubated initially with a stylet. Of these five participants, 80% required use of a GlideScope (P < .001), and they had significantly higher ASA classification (P = .047) and number of intubation attempts (P = .042). One patient sustained an oropharyngeal injury during intubation with a stylet. No participants had laryngeal injury. CONCLUSIONS: Most patients can be intubated successfully using a 5.0 ETT without a stylet. There were no cases of laryngeal trauma with this technique. LEVEL OF EVIDENCE: 2b. PMID- 25123375 TI - A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma. AB - BACKGROUND AND OBJECTIVE: Mesothelioma is an incurable cancer with a rising global incidence. Intrapleural delivery of a commercially available compound made up of proteins produced by Staphylococcus aureus has been used clinically to induce pleurodesis. We investigate if this bacterial compound has anti-tumoural activities against pleural malignancies, in addition to its pleurodesing effect. METHODS: The effects of the treatment on mesothelioma cells were evaluated in vitro and further tested in two validated murine models. RESULTS: This S. aureus bio-product mixture effectively kills mesothelioma cells and induces the release of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and vascular endothelial growth factor from primary human mesothelial cells but not malignant pleural mesothelioma cells in vitro. Intratumoural delivery of the treatment in BALB/c mice induced tumour necrosis and local activation of T cells. Tumour growth was significantly inhibited in the treatment group during and after the treatment period (size of tumour 58.8 +/- 10.3 mm(2) vs 118.3 +/- 6.7 mm(2) from saline controls at day 23, n = 9-12 per group), P < 0.001. Tumour growth resumed on cessation of treatment, confirming the inhibition was treatment related. Treatment benefits were further validated in an orthotopic peritoneal model of mesothelioma and the compound significantly reduced the mesothelioma load (P < 0.05 vs saline controls). Mice in the treatment group had a significant increase in the percentage of activated CD4(+) and CD8(+) T cells in tumour-draining lymph nodes. No histological side-effects were observed with the treatment. CONCLUSIONS: This proof-of-principle study demonstrates promising antitumoural activity of a commercially available compound of S. aureus bio-products against mesothelioma. PMID- 25123376 TI - Porous polymers based on aryleneethynylene building blocks. AB - Porous conjugated polymers are synthesized by metal-catalyzed coupling reactions. The progress for porous polymers when planar or tetrahedral building blocks are connected by alkyne units into novel materials is highlighted. The most prominent reaction for the buildup of the microporous alkyne-bridged polymers is the Sonogashira reaction, connecting alkynes to aromatic iodides or bromides. The availability of the building blocks and the potency of the Sonogashira reaction allow preparing a large variety of intrinsically porous polymeric materials, in which rigid struts connect multipronged centers. The microporous polymers are used as catalysts and as storage materials for gases and sensors. Postfunctionalization schemes, understanding of structure-property relationships, and the quest for high porosity are pertinent. PMID- 25123377 TI - Neurophysiological correlates of eye movement desensitization and reprocessing sessions: preliminary evidence for traumatic memories integration. AB - We have investigated the potential role of eye movement desensitization and reprocessing (EMDR) in enhancing the integration of traumatic memories by measuring EEG coherence, power spectra and autonomic variables before (pre-EMDR) and after (post-EMDR) EMDR sessions during the recall of patient's traumatic memory. Thirteen EMDR sessions of six patients with post-traumatic stress disorder were recorded. EEG analyses were conducted by means of the standardized Low Resolution Electric Tomography (sLORETA) software. Power spectra, EEG coherence and heart rate variability (HRV) were compared between pre- and post EMDR sessions. After EMDR, we observed a significant increase of alpha power in the left inferior temporal gyrus (T = 3.879; P = 0.041) and an increased EEG coherence in beta band between C3 and T5 electrodes (T = 6.358; P < 0.001). Furthermore, a significant increase of HRV in the post-EMDR sessions was also observed (pre-EMDR: 6.38 +/- 6.83; post-EMDR: 2.46 +/- 2.95; U-Test = 45, P = 0.043). Finally, the values of lagged coherence were negatively associated with subjective units of disturbance (r(24) = -0.44, P < 0.05) and positively associated with parasympathetic activity (r(24) = 0.40, P < 0.05). Our results suggest that EMDR leads to an integration of dissociated aspects of traumatic memories and, consequently, a decrease of hyperarousal symptoms [Correction made here after initial publication]. PMID- 25123378 TI - Long term follow-up of four patients with Keutel syndrome. AB - Keutel syndrome (KS) [OMIM 245150] is an autosomal recessive hereditary syndrome characterized by multiple peripheral pulmonary stenoses (PPS), brachytelephalangia, inner ear deafness, and abnormal cartilage ossification or calcification. Mutations in the matrix Gla protein (MGP) gene have been reported in different unrelated families with KS previously. MGP is an extracellular matrix protein and calcification inhibitor; mutations in its encoding gene result in cartilage ossification or calcification, the main presenting feature of KS. This report describes the findings of four sisters with KS born to consanguineous parents were followed for 26 years in an irregular fashion. During follow-up of the patients over the years the complications appear to be mostly involving the respiratory system. Permanent skin rashes, papillary microcarcinoma of the thyroid, asthma, massive bullous pulmonary emphysema, severe systemic arterial hypertension, and short term memory loss were observed during long term follow up. The fertility status of the patients were also observed and infertility was observed in one of three married patients. PMID- 25123379 TI - Incidence of and risk factors for incisional hernia after abdominal surgery. AB - BACKGROUND: Few larger studies have estimated the incidence of incisional hernia (IH) after abdominal surgery. METHODS: Patients who had abdominal surgery between November 2009 and February 2011 were included in the study. The incidence rate and risk factors for IH were monitored for at least 180 days. RESULTS: A total of 4305 consecutive patients were registered. Of these, 378 were excluded because of failure to complete follow-up and 3927 patients were analysed. IH was diagnosed in 318 patients. The estimated incidence rates for IH were 5.2 per cent at 12 months and 10.3 per cent at 24 months. In multivariable analysis, wound classification III and IV (hazard ratio (HR) 2.26, 95 per cent confidence interval 1.52 to 3.35), body mass index of 25 kg/m(2) or higher (HR 1.76, 1.35 to 2.30), midline incision (HR 1.74, 1.28 to 2.38), incisional surgical-site infection (I-SSI) (HR 1.68, 1.24 to 2.28), preoperative chemotherapy (HR 1.61, 1.08 to 2.37), blood transfusion (HR 1.46, 1.04 to 2.05), increasing age by 10 year interval (HR 1.30, 1.16 to 1.45), female sex (HR 1.26, 1.01 to 1.59) and thickness of subcutaneous tissue for every 1-cm increase (HR 1.18, 1.03 to 1.35) were identified as independent risk factors. Compared with superficial I-SSI, deep I-SSI was more strongly associated with the development of IH. CONCLUSION: Although there are several risk factors for IH, reducing I-SSI is an important step in the prevention of IH. REGISTRATION NUMBER: UMIN000004723 (University Hospital Medical Information Network, http://www.umin.ac.jp/ctr/index.htm). PMID- 25123380 TI - Mothering, fathering, and the regulation of negative and positive emotions in high-functioning preschoolers with autism spectrum disorder. AB - BACKGROUND: Children with autism spectrum disorder (ASD) exhibit difficulties in regulating emotions and authors have called to study the specific processes underpinning emotion regulation (ER) in ASD. Yet, little observational research examined the strategies preschoolers with ASD use to regulate negative and positive emotions in the presence of their mothers and fathers. METHODS: Forty preschoolers with ASD and 40 matched typically developing children and their mothers and fathers participated. Families were visited twice for identical battery of paradigms with mother or father. Parent-child interactions were coded for parent and child behaviors and children engaged in ER paradigms eliciting negative (fear) and positive (joy) emotions with each parent. ER paradigms were microcoded for negative and positive emotionality, ER strategies, and parent regulation facilitation. RESULTS: During free play, mothers' and fathers' sensitivity and warm discipline were comparable across groups; however, children with ASD displayed lower positive engagement and higher withdrawal. During ER paradigms, children with ASD expressed less positive emotionality overall and more negative emotionality during fear with father. Children with ASD used more simple self-regulatory strategies, particularly during fear, but expressed comparable levels of assistance seeking behavior toward mother and father in negative and positive contexts. Parents of children with ASD used less complex regulation facilitation strategies, including cognitive reappraisal and emotional reframing, and employed simple tactics, such as physical comforting to manage fear and social gaze to maintain joy. CONCLUSION: Findings describe general and parent- and emotion-specific processes of child ER and parent regulation facilitation in preschoolers with ASD. Results underscore the ability of such children to seek parental assistance during moments of high arousal and the parents' sensitive adaptation to their children's needs. Reduced positive emotionality, rather than increased negative reactivity and self-regulatory efforts, emerges as the consistent element associated with ER processes in this group. PMID- 25123381 TI - Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir. AB - Sofosbuvir (Sovaldi, SOF) is a nucleotide analog prodrug that targets the hepatitis C virus (HCV) nonstructural protein 5B (NS5B) polymerase and inhibits viral replication. High sustained virological response rates are achieved when SOF is used in combination with ribavirin with or without pegylated interferon in subjects with chronic HCV infection. Potential mechanisms of HCV resistance to SOF and other nucleos(t)ide analog NS5B polymerase inhibitors are not well understood. SOF was the first U.S. Food and Drug Administration (FDA)-approved antiviral drug for which genotypic resistance analyses were based almost entirely on next-generation sequencing (NGS), an emerging technology that lacks a standard data analysis pipeline. The FDA Division of Antiviral Products developed an NGS analysis pipeline and performed independent analyses of NGS data from five SOF clinical trials. Additionally, structural bioinformatics approaches were used to characterize potential resistance-associated substitutions. Using protocols we developed, independent analyses of the NGS data reproduced results that were comparable to those reported by Gilead Sciences, Inc. Low-frequency, treatment emergent substitutions occurring at conserved NS5B amino acid positions in subjects who experienced virological failure were also noted and further evaluated. The NS5B substitutions, L159F (sometimes in combination with L320F or C316N) and V321A, emerged in 2.2%-4.4% of subjects who failed SOF treatment across clinical trials. Moreover, baseline polymorphisms at position 316 were potentially associated with reduced response rates in HCV genotype 1b subjects. Analyses of these variants modeled in NS5B crystal structures indicated that all four substitutions could feasibly affect SOF anti-HCV activity. CONCLUSION: SOF has a high barrier to resistance; however, low-frequency NS5B substitutions associated with treatment failure were identified that may contribute to resistance of this important drug for chronic HCV infection. PMID- 25123382 TI - A comparison of airway dimensions, measured by acoustic reflectometry and ultrasound before and after general anaesthesia. AB - Changes in airway dimensions can occur during general anaesthesia and surgery for a variety of reasons. This study explored factors associated with postoperative changes in airway dimensions. Patient airway volume was measured by acoustic reflectometory and neck muscle diameter by ultrasound echography in the pre- and post-anaesthetic periods in a total of 281 patients. Neck circumference was also assessed during these periods. A significant decrease in median (IQR [range]) total airway volume (from 63.8 (51.8-75.7 [14.7-103]) ml to 45.9 (33.5-57.2 [6.4 96.3]) ml, p < 0.0001), and a significant increase in muscle diameter (from 4.3 (3.3-5.6 [2.2-9.0]) mm to 5.8 (4.7-7.3 [2.8-1.3]) mm, p < 0.0001) and neck circumference (from 34.0 (32.5-37.0 [29.5-49.0]) cm to 35.0 (33.5-38.0 [30.5 50.5]) cm, p < 0.0001) were observed. It may be possible that changes in airway volume and neck circumference were influenced by surgical duration or peri operative fluid management (rho) = -0.31 (95% CI -0.24 to -0.01), p = 0.0301, 0.17 (-0.23 to -0.06), p = 0.0038, 0.23 (0.12-0.34), p < 0.0001, and 0.16 (0.05 0.27), p = 0.0062, respectively). The intra-oral space can significantly decrease and neck thickness increase after general anaesthesia, and might increase the risk of difficult laryngoscopy and intubation if airway management is required after extubation following general anaesthesia. PMID- 25123384 TI - Editorial: Ultra violet (UV) exposure and IBD--should more be done to demonstrate an association before trying to find its mechanism? PMID- 25123383 TI - Editorial: Early corticosteroids in ulcerative colitis. PMID- 25123385 TI - Editorial: Early corticosteroids in ulcerative colitis--authors' reply. PMID- 25123386 TI - Editorial: UV exposure and IBD--should more be done to demonstrate an association before trying to find its mechanism? Authors' reply. PMID- 25123387 TI - Editorial: Escalation to weekly dosing in adalimumab-treated patients with active ulcerative colitis. PMID- 25123388 TI - Editorial: Unsedated transnasal endoscopy. PMID- 25123389 TI - Editorial: Metabolomic analysis of breath volatile organic compounds--a new scent for inflammatory bowel disease. PMID- 25123390 TI - Editorial: Gut microbiota and chemotherapy- or radiation-induced gastrointestinal mucositis. PMID- 25123391 TI - Letter: Bismuth quadruple therapy with Pylera for H. pylori infection. PMID- 25123392 TI - Letter: Bismuth quadruple therapy with Pylera for Helicobacter pylori infection- authors' reply. PMID- 25123393 TI - Letter: Herbal hepatotoxicity--an update on traditional Chinese medicine preparations. PMID- 25123394 TI - Letter: Herbal hepatotoxicity--an update on traditional Chinese medicine preparations; authors' reply. PMID- 25123396 TI - Binding of fullerenes to amyloid beta fibrils: size matters. AB - Binding affinity of fullerenes C20, C36, C60, C70 and C84 for amyloid beta fibrils is studied by docking and all-atom molecular dynamics simulations with the Amber force field and water model TIP3P. Using the molecular mechanic-Poisson Boltzmann surface area method one can demonstrate that the binding free energy linearly decreases with the number of carbon atoms of fullerene, i.e. the larger is the fullerene size, the higher is the binding affinity. Overall, fullerenes bind to Abeta9-40 fibrils stronger than to Abeta17-42. The number of water molecules trapped in the interior of 12Abeta9-40 fibrils was found to be lower than inside pentamer 5Abeta17-42. C60 destroys Abeta17-42 fibril structure to a greater extent compared to other fullerenes. Our study revealed that the van der Waals interaction dominates over the electrostatic interaction and non-polar residues of amyloid beta peptides play the significant role in interaction with fullerenes providing novel insight into the development of drug candidates against Alzheimer's disease. PMID- 25123395 TI - Validation of DNA promoter hypermethylation biomarkers in breast cancer--a short report. AB - PURPOSE: DNA promoter hypermethylation of tumor suppressor genes is known to occur early in cancer development, including breast cancer. To improve early breast cancer detection, we aimed to investigate whether the identification of DNA promoter hypermethylation might be of added value. METHODS: The methylation status of a panel of 19 candidate genes (AKR1B1, ALX1, ARHGEF7, FZD10, GHSR, GPX7, GREM1, GSTP1, HOXD1, KL, LHX2, MAL, MGMT, NDRG2, RASGRF2, SFRP1, SFRP2, TM6SF1 and TMEFF2) was determined in formalin-fixed paraffin-embedded normal breast and breast cancer tissue samples using gel-based methylation-specific PCR (MSP). RESULTS: The promoters of the AKR1B1, ALX1, GHSR, GREM1, RASGRF2, SFRP2, TM6SF1 and TMEFF2 genes were found to be significantly differentially methylated in normal versus malignant breast tissues. Based on sensitivity, specificity and logistic regression analyses the best performing genes for detecting breast cancer were identified. Through multivariate analyses, we found that AKR1B1 and TM6SF1 could detect breast cancer with an area under the curve (AUC) of 0.986 in a receiver operating characteristic (ROC) assessment. CONCLUSIONS: Based on our data, we conclude that AKR1B1 and TM6SF1 may serve as candidate methylation biomarkers for early breast cancer detection. Further studies are underway to evaluate the methylation status of these genes in body fluids, including nipple aspirates and blood. PMID- 25123398 TI - Activator-free palladium-catalyzed silylation of aryl chlorides with silylsilatranes. AB - The palladium-catalyzed silylation of aryl chlorides with silylsilatranes proceeds under activator-free conditions; hence, wide functional group compatibility is displayed and boryl and siloxy groups are able to survive. Experimental and computational studies revealed that smooth transmetalation from the silylsilatrane to the arylpalladium chloride is facilitated by strong interaction between the Lewis acidic silicon and the chloride. PMID- 25123397 TI - Profilin as a severe food allergen in allergic patients overexposed to grass pollen. AB - BACKGROUND: Profilins are ubiquitous proteins that act as panallergens in sensitized patients, considered to be mild or incomplete food allergens. The aim of the study was to evaluate the role of profilins as severe food allergens in allergic patients overexposed to grass who were referred for severe food reactions and were sensitized to profilins. METHODS: After a careful in vitro screening, 26 patients were included, classified into two groups, mild (17) and severe reactors (9), based on clinical history and subsequently provoked orally with purified profilin in a double-blind placebo-controlled food challenge setup. RESULTS: A significant number of patients presented severe positive food challenge test reactions at low doses of the allergen profilin. Patients prone to suffer from severe reactions had lower IgG4/IgE ratio to major grass allergens than those who did not. CONCLUSION: Profilins are complete food allergens in food allergic patient populations that are exposed to high levels of grass pollen. This type of patient constitutes an optimal model to understand the link between respiratory and food allergies. The nature of the observed reactions and the low level of allergen eliciting the reactions suggest that intake through the oral mucosa might constitute a relevant route of exposure to food allergens. PMID- 25123399 TI - Triphenylamine groups improve blocking behavior of phenoxazine dyes in cobalt electrolyte-based dye-sensitized solar cells. AB - Novel phenoxazine dyes are successfully introduced as sensitizers into dye sensitized solar cells (DSCs) with cobalt-based electrolyte. In sensitizers with triphenylamine (TPA) groups recombination from electrons in the TiO2 conduction band to the cobalt(III) species is suppressed. The effect of the steric properties of the phenoxazine sensitizers on the overall device performance and on recombination and regeneration processes is compared. Optimized DSCs sensitized with IB2 having two TPA groups in combination with tris(2,2' bipyridyl) cobalt(II/III) yield efficiencies of 6.3%, similar to that of IB3, which is equipped with mutiple alkoxy groups. TH310 with only one TPA group gives lower efficiency and open circuit voltage, while IB1 without TPA groups performs even worse. These results demonstrate that both TPA groups on the IB2 are needed for an efficient blocking effect. These results reveal a possible new role for TPA units in DSC sensitizer design. PMID- 25123400 TI - Stage-specific metabolization of triacylglycerols during seed germination of Sacha Inchi (Plukenetia volubilis L.). AB - BACKGROUND: A detailed study was carried out on Sacha Inchi (Plukenetia volubilis L.) to investigate the mobilization of storage lipids during seed germination. RESULTS: Thin layer chromatography analysis of the total lipids showed a rapid decline in the triacylglycerol (TAG) and diacylglycerol (DAG) contents after the early stages (3-10 days after imbibition (DAI)) followed by a steady breakdown during the later stages (20 and 30 DAI) of germination. Trace amounts of monoacylglycerols (MAG) were identified during the final stage (30 DAI). Further, gas chromatography analysis showed an increase in the major unsaturated fatty acid (linoleic and linolenic) content from 3 to 10 DAI followed by a slow decline. In addition, the major saturated fatty acid (palmitic and oleic) content showed a decrease during the early stages (3-10 DAI) and an increase during the later stages (20 and 30 DAI). CONCLUSION: The present study provides the first report on the metabolization of TAG along with fatty acid changes during the seed germination of Sacha Inchi. PMID- 25123401 TI - Blue SHG enhancement by silver nanocubes photochemically prepared on a RbTiOPO4 ferroelectric crystal. AB - Silver nanocubes with low size dispersion have been selectively photo-deposited on the positive surface of a periodically poled RbTiOPO4 ferroelectric crystal. The obtained nanocubes show preferential orientations with respect to the substrate suggesting epitaxial growth. The plasmonic resonances supported by the nanocubes are exploited to enhance blue SHG at the domain walls. PMID- 25123402 TI - Improving paediatric diabetes care with the use of an integrated paediatric electronic diabetes information management system and routine uploading of blood glucose meters and insulin pumps in outpatient clinics. PMID- 25123403 TI - Why is kernicterus still a major cause of death and disability in low-income and middle-income countries? AB - Neonatal jaundice is predominantly a benign condition that affects 60%-80% of newborns worldwide but progresses to potentially harmful severe hyperbilirubinaemia in some. Despite the proven therapeutic benefits of phototherapy for preventing extreme hyperbilirubinaemia, acute bilirubin encephalopathy or kernicterus, several low-income and middle-income countries (LMIC) continue to report high rates of avoidable exchange transfusions, as well as bilirubin-induced mortality and neurodevelopmental disorders. Considering the critical role of appropriate timing in treatment effectiveness, this review set out to examine the contributory factors to the burden of severe hyperbilirubinaemia and kernicterus based on the 'three delays model' described by Thaddeus and Maine in the 91 most economically disadvantaged LMICs with Gross National Income per capita <=US$6000 and median human development index of 0.525 (IQR: 0.436-0.632). Strategies for addressing these delays are proposed including the need for clinical and public health leadership to curtail the risk and burden of kernicterus in LMICs. PMID- 25123404 TI - Propranolol for infantile haemangiomas: single centre experience of 250 cases and proposed therapeutic protocol. AB - OBJECTIVE: To assess the safety and efficacy of systemic propranolol for the treatment of complicated infantile haemangiomas. DESIGN: Retrospective review of case notes of paediatric patients treated with propranolol for complicated infantile haemangiomas. SETTING: Tertiary care children's hospital. PATIENTS: All paediatric patients with complicated infantile haemangiomas who commenced treatment with propranolol from July 2008 to December 2011 and have completed treatment for at least 3 months. RESULTS: 250 patients were treated with propranolol; 34.4% were premature and 5.6% postmature. Indications for propranolol included: vision compromise (42.0%), bleeding and/or ulceration (30.4%) airway obstruction (8.8%), feeding difficulty (8.4%), risk of permanent disfigurement (4.4%) and other (6%) (nasal obstruction, auditory canal obstruction, large haemangioma, compression of neck structure and spinal cord). Median age at beginning of treatment was 4.5 months. Median age at end of treatment was 16.7 months. Median length of therapy was 11.8 months. Adverse effects (such as wheezing, worsening of ulceration, sleep disturbance, diarrhoea) occurred in 38 patients (15.2%), leading to modifications in management in 26 patients (10.4%). 240 patients (96%) had good to excellent response to treatment. 20 patients (8%) experienced regrowth of the haemangioma on cessation of propranolol and six patients (2.4%) required propranolol to be restarted. CONCLUSIONS: In appropriately selected patients, propranolol is a safe and effective treatment for infantile haemangiomas. PMID- 25123406 TI - Preparation of dithienylphospholes by 1,1-carboboration. AB - In this study the scope of the 1,1-carboboration reaction was extended to the preparation of mixed heterole-based conjugated pi-systems. Two arylbis(alkynyl)phosphane starting materials 2 were synthesized bearing two thiophene isomers at the alkyne units and the bulky tipp-substituent (tipp=2,4,6 triisopropylphenyl) at the phosphorous atom. The bis(thienylethynyl)phosphanes 2 were converted into the corresponding 2,5-thienyl-substituted 3-borylphospholes 4 in a double 1,1-carboboration reaction sequence employing the strongly electrophilic B(C6 F5 )3 reagent under mild reaction conditions. Subsequent Suzuki-Miyaura type cross-coupling yielded the corresponding 3-phenylphospholes 7 in a one-pot procedure from phosphanes 2 in high yields. Phospholes 7 were converted into the respective phosphole oxides 8. A photophysical characterization of derivatives 7 and 8 was carried out. The results presented here demonstrate the suitability of the 1,1-carboboration reaction for the preparation of phosphole-/thiophene-based, light-emitting systems. PMID- 25123405 TI - Successful outcome of renal transplantation in a child with HIV-associated nephropathy. AB - Classical HIV-associated nephropathy (HIVAN) was first described before the advent of highly active antiretroviral therapy in late stages of HIV disease with high viral load and low CD4 cell count. Renal transplantation has been successful in a large series of carefully selected HIV-infected adults, with patient and renal allograft survival approaching those of non-HIV-infected patients. We report the successful outcome of living related renal transplantation in a vertically transmitted HIV-infected 8-year-old girl with end-stage kidney disease on haemodialysis due to HIVAN. The pretransplant preparations and post-transplant care, with particular emphasis on immunosuppression and avoidance of opportunistic infections, are discussed. PMID- 25123407 TI - Fullerene growth from encapsulated graphene flakes. AB - The direct in situ observation of fullerene formation encapsulated within a graphene ridge has been made possible using an aberration corrected transmission electron microscope (AC-TEM). An atom-by-atom mechanism was proposed based on in situ AC-TEM observations. First principle calculations found a continuous energy decrease upon the addition of carbon atoms to the edge of the graphene flakes, which mimics the fullerene growth steps and supports the atom-by-atom mechanism. The ridged graphene structure worked as a container for pinning small graphene flakes and capturing carbon atoms, which increased the growth probability of the fullerene structure within the small encapsulated space. PMID- 25123408 TI - Genomic medicine: a question of value: despite the promise of personalized medicine, genomic testing has yet to prove its cost-effectiveness. PMID- 25123409 TI - Complications related to harvest of the proximal end of the fibula: a systematic review. AB - BACKGROUND: The fibula is a common source of bone graft used in skeletal reconstruction. Although in most cases only the diaphysis of the fibula is used, there are clinical scenarios in which the proximal end of the fibula and fibular head are harvested for use in articular reconstruction. The purpose of this systematic review is to determine the incidence of knee instability and peroneal nerve motor dysfunction associated with removal of the proximal end of the fibula and fibular head. METHODS: A systematic search was performed using the PubMed, Ovid MEDLINE, and cochrane databases. Studies accepted for review included those that clearly reported donor site morbidity (instability or peroneal nerve motor dysfunction) after proximal fibula resection. All studies in which the proximal fibula was resected for bone graft or for marginal resection of tumor were included. RESULTS: Fifteen studies reporting a total of 337 patients were included. The rate of symptomatic knee instability after proximal fibula resection was 3.9%. The incidence of instability that was detectible on physical examination or stress radiographs was higher. Although transient motor dysfunction was not uncommon, the incidence of persistent peroneal nerve motor dysfunction was 2.6%. CONCLUSION: Although asymptomatic laxity is common, the incidence of symptomatic knee instability after resection of the proximal fibula is relatively low. The incidence of persistent peroneal nerve motor dysfunction is also low when the nerve is intentionally protected during surgery. PMID- 25123410 TI - A national study on adherence to a basal cell carcinoma guideline; development of a tool to assess guideline adherence. AB - BACKGROUND: Clinical practice guideline implementation may be at variance with actual daily practice, as guideline adherence is a complex process depending on many actors and factors. Feedback regarding adherence is essential to monitor the effect that a guideline has in clinical practice and whether or not the quality of care is raised by implementation. OBJECTIVES: Developing a tool for obtaining and giving nationwide feedback regarding adherence. METHODS: From February 2010 to June 2013, a 32-item questionnaire was used as an audit tool during committee visits to assess adherence across 37 dermatological centres in The Netherlands. The questions were derived from the recommendations by the Dutch Dermatological and Venereological Society (NVDV) in the Dutch Basal Cell Carcinoma (BCC) guideline. Five selected medical records per dermatologist were audited and the results were discussed with the audited centre. Data were pooled to calculate the compliance with each recommendation across all participating centres. RESULTS: Adherence to recommended actions varied considerably (20.2-100%) across the domains of prevention, diagnostics, treatments and aftercare. Using and reporting surgical margins, giving patient advice, restricting the use of cryosurgery for certain BCCs and reporting on prognostic factors all failed to reach a threshold of 80%. Nonadherence to recommended actions proved to be related to whether or not a dermatologist was directly involved. CONCLUSIONS: The findings emphasize the importance of direct feedback to practitioners regarding adherence. Furthermore, together with existing frameworks, the method described could be used by developers in a guideline update to identify and anticipate barriers to successful implementation. PMID- 25123411 TI - Simultaneous flow cytometric analysis of IFN-gamma and CD4 mRNA and protein expression kinetics in human peripheral blood mononuclear cells during activation. AB - The application of fluorescently-labeled antibodies for flow cytometric identification and characterization of specific cell types within heterogeneous populations by their protein expression profile is well established. While detection of proteins is informative, concomitant transcript analysis in the same cells would provide a more complete and comprehensive view of intracellular signaling events. We recently reported on the efficient detection of RNA in suspension cells for flow cytometric analysis. The improved RNA flow cytometry procedure described here allows for the specific labeling of multiple RNA species, and is compatible with antibody-based targeting of extracellular and intracellular antigens for multiplexing purposes. To show proof of concept, human peripheral blood mononuclear cells were stimulated with phorbol 12-myristate 13 acetate and ionomycin for a maximum of 5 h, during which their CD4 and interferon gamma (IFN-gamma) transcript and protein levels were monitored. Substantial and increasing numbers of IFN-gamma mRNA+ cells were detected within 30 min after initiation of induction, while IFN-gamma protein+ cells could only be discerned at 1 h and beyond. Surprisingly, resting lymphocytes contained less CD4 mRNA but more of the protein per cell compared with monocytes, revealing a difference in the relationship of transcript and protein levels in these two cell types. We additionally applied monensin, which is commonly used to block cytokine secretion, and found that IFN-gamma mRNA can still be analyzed consistently using the improved RNA flow cytometry staining method. Notably, a subset of IFN-gamma mRNA(-)/protein+ cells that were not observed in the absence of monensin became apparent at the 5-h mark. This subset probably represents cells that have accumulated IFN-gamma protein, but no longer transcribe mRNA. Collectively, the results described here exemplify how the improved RNA flow cytometry labeling procedure can be applied to simultaneously assess mRNA and protein dynamics to gain insight into the regulation of gene transcription and translation in individual cells. PMID- 25123412 TI - Screening for prostate cancer in the US? Reduce the harms and keep the benefit. AB - While the benefit of prostate-specific antigen (PSA) based screening is uncertain, a significant proportion of screen-detected cases is overdiagnosed. In order to make screening worthwhile, it is necessary to find policies that minimize overdiagnosis, without significantly increasing prostate cancer mortality (PCM). Using a microsimulation model (MISCAN) we project the outcomes of 83 screening policies in the US population, with different start and stop ages, screening frequencies, strategies where the PSA value changes the screening frequency, and strategies in which the PSA threshold (PSAt) increases with age. In the basecase strategy, yearly screening 50-74 with a PSAt of 3, the lifetime risk of PCM and overdiagnosis equals, respectively, 2.4 and 3.8%. The policies that reduce overdiagnosis the most (for maximum PCM increases relative to basecase of 1%, 3%, and 5%, respectively) are with a PSAt of 3, (1) yearly screening 50-74 where, if PSA <1 at age 65 or older, frequency becomes 4 years, with 3.6% (5.9% reduction), (2) 2-year screening 50-72, with 2.9% (24.3% reduction), and (3) yearly screening 50-70 (PSAt of 4 after age 66), with 2.2% (43.4% reduction). Stopping screening at age 70 is a reasonable way to reduce the harms and keep the benefit. Decreasing the stopping age has a larger effect on overdiagnosis reduction than reducing the screen frequency. Screening policies where the frequency of screening depends on PSA result or in which the PSAt changes with age did not substantially improve the balance of harms and benefits relative to simple yearly screening. PMID- 25123413 TI - Effect of physicochemical factors on glycerol production by simultaneous cultures of wine micro-organisms using the response surface method. AB - AIM: To evaluate the effect of temperature, pH and SO2 on growth and glycerol production improvement by Saccharomyces cerevisiae mc2, Kloeckera apiculata mF and Oenococcus oeni X2L using the response surface method (RSM). METHODS AND RESULTS: Multifactorial design of cultures with physicochemical factors variations was performed. The micro-organisms grew in all cultures conditions. Overall, after 6 days yeasts prevailed, especially S. cerevisiae (10(9) CFU ml( 1)), while O. oeni reached 10(7) CFU ml(-1). At initial fixed pH 5.5, metabolic behaviour of cultures showed a temperature-dependent response. Total malate consumption occurred at 26 degrees C, 50 mg l(-1) SO2. Glucose and pentoses utilization was highly modified when varying SO2. Ethanol showed negative interaction with temperature-SO2 relationship. At low SO2, glycerol and acetate production increased when temperature enhanced. Predictive results of RSM indicate that 26 degrees C, 60.24 mg l(-1) SO2 and pH 5.5 were the optimal conditions for glycerol and organic acids synthesis compatible with wine quality. CONCLUSIONS: We propose a predictive condition to improve the performance of mixed cultures for must fermentations. SIGNIFICANCE AND IMPACT OF THE STUDY: To optimize the culture conditions to design mixed starters containing autochthonous yeasts and O. oeni strains for winemaking and to obtain products with high glycerol content, low acidity and maintenance of regional characteristics. PMID- 25123414 TI - Sub-crestal positioning of implants results in higher bony crest resorption: an experimental study in dogs. AB - OBJECTIVE: To compare peri-implant soft- and hard-tissue integration at implants installed juxta- or sub-crestally. Furthermore, differences in the hard and soft peri-implant tissue dimensions at sites prepared with drills or sonic instruments were to be evaluated. MATERIAL AND METHODS: Three months after tooth extraction in six dogs, recipient sites were prepared in both sides of the mandible using conventional drills or a sonic device (Sonosurgery((r))). Two implants with a 1.7 mm high-polished neck were installed, one with the rough/smooth surface interface placed at the level of the buccal bony crest (control) and the second placed 1.3 mm deeper (test). After 8 weeks of non-submerged healing, biopsies were harvested and ground sections prepared for histological evaluation. RESULTS: The buccal distances between the abutment/fixture junction (AF) and the most coronal level of osseointegration (B) were 1.6 +/- 0.6 and 2.4 +/- 0.4 mm; between AF and the top of the bony crest (C), they were 1.4 +/- 0.4 and 2.2 +/- 0.2 mm at the test and control sites, respectively. The top of the peri-implant mucosa (PM) was located more coronally at the test (1.2 +/- 0.6 mm) compared to the control sites (0.6 +/- 0.5 mm). However, when the original position of the bony crest was taken into account, a higher bone loss and a more apical position of the peri-implant mucosa resulted at the test sites. CONCLUSIONS: The placement of implants into a sub-crestal location resulted in a higher vertical buccal bone resorption and a more apical position of the peri-implant mucosa in relation to the level of the bony crest at implant installation. Moreover, peri-implant hard-tissue dimensions were similar at sites prepared with either drills or Sonosurgery((r)). PMID- 25123415 TI - Mosaic activity patterns and their relation to perceptual similarity: open discussions on the molecular basis and circuitry of odor recognition. AB - Enormous advances have been made in the recent years in regard to the mechanisms and neural circuits by which odors are sensed and perceived. Part of this understanding has been gained from parallel studies in insects and rodents that show striking similarity in the mechanisms they use to sense, encode, and perceive odors. In this review, we provide a short introduction to the functioning of olfactory systems from transduction of odorant stimuli into electrical signals in sensory neurons to the anatomical and functional organization of the networks involved in neural representation of odors in the central nervous system. We make emphasis on the functional and anatomical architecture of the first synaptic relay of the olfactory circuit, the olfactory bulb in vertebrates and the antennal lobe in insects. We discuss how the exquisite and conserved architecture of this structure is established and how different odors are encoded in mosaic activity patterns. Finally, we discuss the validity of methods used to compare activation patterns in relation to perceptual similarity. PMID- 25123417 TI - Epidemiological research on the incidence and prevalence of arterial hypertension in the Portuguese population: a scoping review. AB - INTRODUCTION AND OBJECTIVES: The Portuguese population is reported to have among the highest levels of mean blood pressure. The aim of the present study is to conduct a structured literature review describing the scope (quantity, focus and nature) of published epidemiological research on the prevalence and incidence of hypertension in the Portuguese population. METHODS: The scoping review was conducted during June 2013, using two information sources, B-on and PubMed, to search for published studies on the prevalence and incidence of hypertension with data collected between 2005-2013 and 1995-2013, respectively. RESULTS: We identified 527 publications: 14 on the prevalence and two on the incidence of hypertension. The results show more studies on populations in the North region of Portugal; an apparent lack of published studies specifically targeting the Alentejo and Algarve populations; long delays between data collection and publication of results (up to nine years); considerable variability in measurement methods; and infrequent data stratification by gender and age. CONCLUSIONS: Differences in blood pressure measurement methods, not specified in most studies, the infrequency of stratification of results by gender and age, and the geographic asymmetry in coverage of the Portuguese population, hinder monitoring of the incidence and prevalence of hypertension in Portugal. PMID- 25123416 TI - Synthesis and evaluation of translocator 18 kDa protein (TSPO) positron emission tomography (PET) radioligands with low binding sensitivity to human single nucleotide polymorphism rs6971. AB - The imaging of translocator 18 kDa protein (TSPO) in living human brain with radioligands by positron emission tomography (PET) has become an important means for the study of neuroinflammatory conditions occurring in several neuropsychiatric disorders. The widely used prototypical PET radioligand [(11)C](R)-PK 11195 ([(11)C](R)-1; [N-methyl-(11)C](R)-N-sec-butyl-1-(2 chlorophenyl)-N-methylisoquinoline-3-carboxamide) gives a low PET signal and is difficult to quantify, whereas later generation radioligands have binding sensitivity to a human single nucleotide polymorphism (SNP) rs6971, which imposes limitations on their utility for comparative quantitative PET studies of normal and diseased subjects. Recently, azaisosteres of 1 have been developed with improved drug-like properties, including enhanced TSPO affinity accompanied by moderated lipophilicity. Here we selected three of these new ligands (7-9) for labeling with carbon-11 and for evaluation in monkey as candidate PET radioligands for imaging brain TSPO. Each radioligand was readily prepared by (11)C-methylation of an N-desmethyl precursor and was found to give a high proportion of TSPO-specific binding in monkey brain. One of these radioligands, [(11)C]7, the direct 4-azaisostere of 1, presents many radioligand properties that are superior to those reported for [(11)C]1, including higher affinity, lower lipophilicity, and stable quantifiable PET signal. Importantly, 7 was also found to show very low sensitivity to the human SNP rs6971 in vitro. Therefore, [(11)C]7 now warrants evaluation in human subjects with PET to assess its utility for imaging TSPO in human brain, irrespective of subject genotype. PMID- 25123418 TI - Staff's person-centredness in dementia care in relation to job characteristics and job-related well-being: a cross-sectional survey in nursing homes. AB - AIM: To explore the role of nursing staff's person-centredness caring for people with dementia in relation to their work environment and job-related well-being. BACKGROUND: Given the development towards person-centred care and labour force issues, research has recently focused on the effect of person-centredness on nursing staff's well-being. Findings from occupational stress research suggest that employees' personal characteristics, such as person-centredness, can moderate the impact particular job characteristics have on their job-related well being. DESIGN: Cross-sectional survey. METHODS: A national survey was conducted among healthcare staff (n = 1147) in 136 living arrangements for people with dementia in the Netherlands (2008-2009). Hierarchical regression analyses were used. RESULTS: Person-centredness moderates the relationship between coworker support and three outcomes of job-related well-being and between supervisor support and two of these outcomes. For highly person-centred nursing staff, coworker support was found to have a weaker impact and supervisor support to have a stronger impact on their job-related well-being. In addition, direct effects showed that person-centredness was weakly associated with more job satisfaction, more emotional exhaustion and more strongly with more personal accomplishment. CONCLUSION: Nursing staff's person-centredness does play a modest role in relation to job characteristics and job-related well-being. Findings indicate that person-centredness is not only beneficial to residents with dementia as found earlier, but also for nursing staff themselves; specifically, in case nursing staff members feel supported by their supervisor. Since a more person centred workforce feels more competent, further implementation of person-centred care might have a positive impact on the attractiveness of the profession. PMID- 25123419 TI - Pilomatricoma of the male breast: sonographic mammographic MRI features with pathologic correlation. AB - We report a case of 43-year-old man who presented with an enlarging, painless, palpable mass in the left breast for one year associated with surface blue discoloration of the skin. Mammogram showed a well-defined 2.3-cm mass with microcalcifications. Ultrasound revealed a well-defined, subcutaneous hypoechoic mass adherent to the skin with multiple bright foci. Ultrasound-guided needle biopsy produced a dark-colored sample corresponding to pilomatricoma on final pathology. Bilateral breast magnetic resonance imaging showed heterogeneously hyperintense in T1- and T2-weighted images with heterogeneous enhancement toward the delayed phase. Surgical resection was carried out with wide margins. PMID- 25123420 TI - Retro-ureteral internal hernia after transperitoneal ureter reimplantation: an unusual cause of small bowel obstruction. AB - Report of a case of surgically confirmed closed-loop small bowel obstruction due to internal hernia following transperitoneal ureter reimplantation. Multidetector computed tomography (CT) demonstrated the presence and the cause of this unusual postsurgical internal hernia. The CT findings are presented herein. PMID- 25123421 TI - Chronic recurrent multifocal osteomyelitis complicated by hip subluxation: a case report. PMID- 25123422 TI - Cytological follow-up after hysterectomy: is vaginal vault cytology sampling a clinical governance problem? The University Hospital of North Staffordshire approach. AB - OBJECTIVES: Vaginal vault cytology sampling following hysterectomy is recommended for specific indications in national guidelines. However, clinical governance issues surround compliance with guidance. Our first study objective was to quantify how many patients undergoing hysterectomy at the University Hospital of North Staffordshire (UHNS) had vault cytology advice in their histology report and, if indicated, whether it was arranged. The second was to devise a vault cytology protocol based on local experience and national guidance. METHODS: The local cancer registry was searched. Clinical, clerical and histological data for all patients undergoing hysterectomy were collected. RESULTS: In total, 271 patients were identified from both the gynae-oncology and benign gynaecology teams. Of these, 24% (65/271) were gynae-oncology patients with a mean age of 69 years. The benign gynaecology team had 76% (206/271) of patients with a mean age of 55 years. Subsequently, 94% (256/271) had cytology follow-up advice in their histopathology report. Ultimately, from both cohorts, 39% (18/46) had follow-up cytology performed when indicated. CONCLUSION: A high proportion of cases complied with national guidance. However, a disappointingly high number did not have vault cytology sampling when this was indicated. This is probably a result of the complex guidance that is misunderstood in both primary and secondary care. Vault follow-up of patients after hysterectomy rests with the team performing the surgery. Vault cytology, if indicated, should be performed in secondary care and follow-up should be planned. The protocol set out in this article should be followed to avoid unnecessary clinical governance failings. PMID- 25123423 TI - Sulphate fertilization ameliorates long-term aluminum toxicity symptoms in perennial ryegrass (Lolium perenne). AB - Effects of the oxanion sulphate on plant aluminum (Al(3+)) detoxification mechanisms are not well understood. Therefore, holistic physiological and biochemical modifications induced by progressively increased doses of sulphate fertilization in the presence of long-term Al(3+) stress were investigated in the aluminum sensitive perennial ryegrass (Lolium perenne L. cvJumbo). Plant growth inhibition induced by Al(3+) was decreased in response to increasing doses of sulphate supply. Aluminum concentrations measured in roots of perennial ryegrass by atomic absorption spectrometry declined significantly with increasing sulphate concentrations. In parallel, we determined a rise of sulphur in shoots and roots of perennial ryegrass. Inclusion of up to 360 MUM of sulphate enhanced cysteine and glutathione biosynthesis in Al(3+) (1.07 MUM) treated plants. This increase of thiol-containing compounds favored all modifications in the glutathione redox balance, declining lipid peroxidation, decreasing the activity of superoxide dismutase, and modifying the expression of proteins involved in the diminution of Al(3+) toxicity in roots. In particular, proteome analysis by 1D-SDS-PAGE and LC MS/MS allowed to identify up (e.g. vacuolar proton ATPase, proteosome beta subunit, etc) and down (Glyoxilase I, Ascorbate peroxidase, etc.) regulated proteins induced by Al(3+) toxicity symptoms in roots. Although, sulphate supply up to 480 MUM caused a reduction in Al(3+) toxicity symptoms, it was not as efficient as compared to 360 MUM sulphate fertilization. These results suggest that sulphate fertilization ameliorates Al(3+) toxicity responses in an intracellular specific manner within Lolium perenne. PMID- 25123424 TI - Delphi consensus on the current clinical and therapeutic knowledge on Anderson Fabry disease. AB - BACKGROUND: Management of Anderson-Fabry disease (AFD) is contentious, particularly regarding enzyme replacement therapy (ERT). We report results of a Delphi consensus panel on AFD management. METHODS: A survey to gauge consensus among AFD experts was distributed online and responses were analysed. Statements on: 1) diagnosis; 2) when starting ERT; 3) management of ERT infusion and adverse reactions; and 4) follow-up/monitoring response to therapy and progression of disease were included. Responses without consensus were discussed with an enlarged panel and modified to reach consensus. RESULTS: 15 experts responded to the survey. After plenary discussion among the enlarged panel, consensus was reached on most statements. Key points were the use of a target organ biopsy to show Gb3 deposits in symptomatic women with negative molecular analysis, the need for ERT in symptomatic women and in all patients with persistent signs and symptoms +/- organ damage. It was agreed to assess vital signs before ERT administration and use a 0.2 MUL filter on infusion to reduce the risk of adverse reactions, that serum should be drawn prior to the first infusion for anti agalsidase antibody analysis to have a baseline value if a subsequent adverse reaction appears, and that pre-medication is required in those with prior infusion reactions. Holter ECG monitoring, cardiac and brain MRI, renal parameters, and abdominal ultrasound were considered important for the assessment of disease progression and response at ERT. CONCLUSIONS: This consensus supplies guidance to healthcare providers on best practice in the management of patients with AFD and indicates a need for more guidance. PMID- 25123425 TI - Prevalence of malnutrition, obesity and nutritional risk of Australian paediatric inpatients: a national one-day snapshot. AB - AIM: Low prevalence rates of malnutrition at 2.5% to 4% have previously been reported in two tertiary paediatric Australian hospitals. The current study is the first to measure the prevalence of malnutrition, obesity and nutritional risk of paediatric inpatients in multiple hospitals throughout Australia. METHODS: Malnutrition, obesity and nutritional risk prevalence were investigated in 832 and 570 paediatric inpatients, respectively, in eight tertiary paediatric hospitals and eight regional hospitals across Australia on a single day. Malnutrition and obesity prevalence was determined using z-scores and body mass index (BMI) percentiles. High nutritional risk was determined as a Paediatric Yorkhill Malnutrition Score of 2 or more. RESULTS: The prevalence rates of malnourished, wasted, stunted, overweight and obese paediatric patients were 15%, 13.8%, 11.9%, 8.8% and 9.9%, respectively. Patients who identified as Aboriginal and Torres Strait Islander were more likely to have lower height-for-age z-scores (P < 0.01); however, BMI and weight-for-age z-scores were not significantly different. Children who were younger, from regional hospitals or with a primary diagnosis of cardiac disease or cystic fibrosis had significantly lower anthropometric z-scores (P = 0.05). Forty-four per cent of patients were identified as at high nutritional risk and requiring further nutritional assessment. CONCLUSIONS: The prevalence of malnutrition and nutritional risk of Australian paediatric inpatients on a given day was much higher when compared with the healthy population. In contrast, the proportion of overweight and obese patients was less. PMID- 25123426 TI - Cytotoxic effects of escin on human castration-resistant prostate cancer cells through the induction of apoptosis and G2/M cell cycle arrest. AB - OBJECTIVE: To evaluate the in vitro and in vivo effects of escin on human castration-resistant prostate cancer (CRPC) cells, PC-3 and DU-145. MATERIALS AND METHODS: The inhibition of cell proliferation and its mechanism were assessed through a cytotoxicity assay, flow cytometry, and Western blot. The in vivo efficacy of escin in CRPC cells was assessed using a xenograft tumor model subcutaneously established in BALB/c nude mice. RESULTS: The treatment with escin significantly reduced cell viability of CRPC cells in a dose- and time-dependent manner. Escin induced apoptosis in a time-dependent manner, which was accompanied by increases in pro-apoptotic (BCL-2 associated X protein, cleaved-caspase3, and cleaved-poly [adenosine diphosphate-ribose] polymerase) proteins and decreases in antiapoptotic (X-linked inhibitor of apoptosis protein, cellular inhibitor of apoptosis protein-1, cellular inhibitor of apoptosis protein-2B-cell leukemia/lymphoma-2, and B-cell lymphoma-extra large) proteins. Escin induced G2/M-phase cell cycle arrest and thus led to a significant decrease in the expression of cyclinB1 and its activating partner cyclin-dependent kinase 1, with the concomitant induction of p21. In addition, escin significantly inhibited the growth of CRPC cells in xenograft models. CONCLUSION: The results show that escin induced cytotoxic effects on CRPC cells through the induction of apoptosis and G2/M cell cycle arrest, indicating it may be a novel therapeutic agent for CRPC. PMID- 25123427 TI - The antitumor effect of suicide gene therapy using Bifidobacterium infantis mediated herpes simplex virus thymidine kinase/ganciclovir in a nude mice model of renal cell carcinoma. AB - OBJECTIVE: To confirm the effectivity of Bifidobacterium infantis-mediated herpes simplex virus thymidine kinase/ganciclovir suicide gene system on the treatment of renal cell carcinoma in nude mice and further explore the mechanisms. MATERIALS AND METHODS: A B infantis thymidine kinase (B infantis-TK) suicide gene system was constructed in our previous study. Tumor-bearing nude mice were randomized into 4 groups and injected with normal saline, B infantis, B infantis/pGEX-1lambdaT, and B infantis-TK, respectively, via tail vein, followed by intraperitoneal injection of ganciclovir. The treatment effects were evaluated by the terminal deoxynucleotidyl transferase-mediated deoxynucleotide triphosphate nick end labeling assay, quantitative reverse transcriptase polymerase chain reaction, and Western blotting. Side effects were also recorded. RESULTS: Compared with the other 3 treatments, the treatment with B infantis-TK resulted in a significant effective antitumor activity and stronger apoptotic response. Western blot analysis showed that the expression levels of Rel A and Bcl-xL were significantly lower, whereas those of caspase 3 and Bax were significantly higher in tumor tissues resected from group B infantis-TK, which were consistent with the quantitative reverse transcriptase-polymerase chain reaction results. CONCLUSION: The B infantis-TK/ganciclovir therapy system exhibits an effective antitumor activity by promoting tumor cell apoptosis through both the intrinsic and the extrinsic apoptotic pathways. PMID- 25123428 TI - Gossypiboma mimicking a retroperitoneal tumor. AB - "Gossypiboma" denotes a mass of cotton that is retained in the body after surgery. An image is presented of a retroperitoneal mass in a lady who had a right nephrectomy 8 years earlier for a nonfunctioning kidney. Clinical examination and plain abdominal radiography were not contributory. Contrast enhanced abdominal computed tomography revealed a well-defined, heterogeneous, spherical, soft-tissue mass, 13 * 9 * 9 cm in size, in the retroperitoneum, with a dense enhanced wall, abutting the right psoas and posterior abdominal wall. Exploration revealed an abdominal sponge surrounded by foreign body granuloma adherent to surrounding structures. Gossypiboma can mimic a tumor and is a diagnostic challenge. PMID- 25123429 TI - Comparison of radiation dose from conventional and triple-bolus computed tomography urography protocols in the diagnosis and management of patients with renal cortical neoplasms. AB - OBJECTIVE: To retrospectively compare the radiation dose of triple-bolus computed tomography (TBCT) and conventional CT (CCT) urography protocols, analyze the effects of body mass index (BMI) on radiation dose in each group, and assess image quality. MATERIALS AND METHODS: We retrospectively reviewed the images of patients who underwent CCT or TBCT imaging in the management of renal cortical neoplasms. We used standard volumetric CT dose index (CTDIvol) and dose length product (DLP) to estimate radiation exposure. In addition, 2 urologists rated the quality of 20 CT images from each group using a survey with a 5-point Likert scale. The survey consisted of 10 questions relating to the ability of the scan to identify relevant renal anatomy. RESULTS: The study included 120 patients. CTDIvol and DLP were 28.7% and 40.4% lower in the TBCT protocol, respectively (both P < .001). Increased BMI was associated with a higher DLP for the CCT group compared with the TBCT group (P < .001). The effect of BMI on CTDIvol did not differ between the CCT and TBCT groups. There was no difference in the urologists' assessments of CT image quality. CONCLUSION: In patients with renal cortical neoplasms, TBCT provides comparable image quality to CCT, with lower ionizing radiation exposure without compromising image quality. Obese patients may benefit more from TBCT scans. PMID- 25123431 TI - Differential synaptic distribution of the scaffold proteins Cask and Caskin1 in the bovine retina. AB - Scaffold proteins organize pre- and postsynaptic compartments and align pre- and postsynaptic events. Cask is a multi-domain scaffold protein essential for brain synaptic functions. Caskin1 is a recently discovered, brain-specific Cask interacting multi-domain protein of unknown function. In the present study, we determined the localization of these scaffold proteins in the bovine retina. The retina contains tonically active ribbon synapses and conventional synapses. We found Cask highly enriched in virtually all retinal synapses. Cask was localized in close vicinity to the active zone protein RIM1/2 in ribbon and conventional synapses. Caskin1 is also enriched in retinal synapses but is present only in a subset of Cask-positive synapses. These findings suggest that Cask plays an important role in all retinal synapses. In contrast, Caskin1 appears to execute more specialized functions in distinct sets of retinal synapses, possibly for neuronal pathway formation and stabilization of distinct synaptic contacts. PMID- 25123432 TI - Landmark-free statistical analysis of the shape of plant leaves. AB - The shapes of plant leaves are important features to biologists, as they can help in distinguishing plant species, measuring their health, analyzing their growth patterns, and understanding relations between various species. Most of the methods that have been developed in the past focus on comparing the shape of individual leaves using either descriptors or finite sets of landmarks. However, descriptor-based representations are not invertible and thus it is often hard to map descriptor variability into shape variability. On the other hand, landmark based techniques require automatic detection and registration of the landmarks, which is very challenging in the case of plant leaves that exhibit high variability within and across species. In this paper, we propose a statistical model based on the Squared Root Velocity Function (SRVF) representation and the Riemannian elastic metric of Srivastava et al. (2011) to model the observed continuous variability in the shape of plant leaves. We treat plant species as random variables on a non-linear shape manifold and thus statistical summaries, such as means and covariances, can be computed. One can then study the principal modes of variations and characterize the observed shapes using probability density models, such as Gaussians or Mixture of Gaussians. We demonstrate the usage of such statistical model for (1) efficient classification of individual leaves, (2) the exploration of the space of plant leaf shapes, which is important in the study of population-specific variations, and (3) comparing entire plant species, which is fundamental to the study of evolutionary relationships in plants. Our approach does not require descriptors or landmarks but automatically solves for the optimal registration that aligns a pair of shapes. We evaluate the performance of the proposed framework on publicly available benchmarks such as the Flavia, the Swedish, and the ImageCLEF2011 plant leaf datasets. PMID- 25123430 TI - The hepatitis B virus e antigen suppresses the respiratory burst and mobility of human monocytes and neutrophils. AB - The Hepatitis B virus (HBV) e antigen (HBeAg) is a secretory, non-structural protein, and associated with persistent infection of HBV. Previous studies indicate that HBeAg is able to regulate T cell-mediated responses, however, the interaction between HBeAg and the innate immune system is poorly understood. In this study, we demonstrated that recombinant HBeAg (rHBe) bound to human peripheral blood monocytes, neutrophils, and B lymphocytes but not to T lymphocytes. We focused on investigating the effects of HBeAg on monocytes and neutrophils and found that rHBe decreased the respiratory burst in both types of cells. Furthermore, we observed that cell migration in monocytes and neutrophils was suppressed by rHBe in a transwell assay. The attenuation of rHBe was not caused by a general cytotoxic effect because rHBe treatment stimulated low levels of cytokine and chemokine production by monocytes and it promoted neutrophil survival. Since the recruitment of monocytes and neutrophils to the infected site is crucial for the initiation of inflammation, HBeAg may modulate innate immune responses by diminishing the respiratory burst and migration of monocytes and neutrophils, which might interfere with the subsequent innate and adaptive immune responses against HBV, leading to the establishment of chronic infection. PMID- 25123433 TI - PECM: prediction of extracellular matrix proteins using the concept of Chou's pseudo amino acid composition. AB - The extracellular matrix proteins (ECMs) are widely found in the tissues of multicellular organisms. They consist of various secreted proteins, mainly polysaccharides and glycoproteins. The ECMs involve the exchange of materials and information between resident cells and the external environment. Accurate identification of ECMs is a significant step in understanding the evolution of cancer as well as promises wide range of potential applications in therapeutic targets or diagnostic markers. In this paper, an accurate computational method named PECM is proposed for identifying ECMs. Here, we explore various sequence derived discriminative features including evolutionary information, predicted secondary structure, and physicochemical properties. Rather than simply combining the features which may bring information redundancy and unwanted noises, we use Fisher-Markov selector and incremental feature selection approach to search the optimal feature subsets. Then, we train our model by the technique of support vector machine (SVM). PECM achieves good prediction performance with the ACC scores about 86% and 90% on testing and independent datasets, which are competitive with the state-of-the-art ECMs prediction tools. A web-server named PECM which implements the proposed approach is freely available at http://59.73.198.144:8088/PECM/. PMID- 25123434 TI - Failure analysis of porcupine quills under axial compression reveals their mechanical response during buckling. AB - Porcupine quills are natural structures formed by a thin walled conical shell and an inner foam core. Axial compression tests, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FT-IR) were all used to compare the characteristics and mechanical properties of porcupine quills with and without core. The failure mechanisms that occur during buckling were analyzed by scanning electron microscopy (SEM), and it was found that delamination buckling is mostly responsible for the decrease in the measured buckling stress of the quills with regard to predicted theoretical values. Our analysis also confirmed that the foam core works as an energy dissipater improving the mechanical response of an empty cylindrical shell, retarding the onset of buckling as well as producing a step wise decrease in force after buckling, instead of an instantaneous decrease in force typical for specimens without core. Cell collapse and cell densification in the inner foam core were identified as the key mechanisms that allow for energy absorption during buckling. PMID- 25123435 TI - Fracture mechanics analyses of ceramic/veneer interface under mixed-mode loading. AB - Few studies have focused on the interface fracture performance of zirconia/veneer bilayered structure, which plays an important role in dental all-ceramic restorations. The purpose of this study was to evaluate the fracture mechanics performance of zirconia/veneer interface in a wide range of mode-mixities (at phase angles ranging from 0 degrees to 90 degrees ), and to examine the effect of mechanical properties of the materials and the interface on the fracture initiation and crack path of an interfacial crack. A modified sandwich test configuration with an oblique interfacial crack was proposed and calibrated to choose the appropriate geometry dimensions by means of finite element analysis. The specimens with different interface inclination angles were tested to failure under three-point bending configuration. Interface fracture parameters were obtained with finite element analyses. Based on the interfacial fracture mechanics, three fracture criteria for crack kinking were used to predict crack initiation and propagation. In addition, the effects of residual stresses due to coefficient of thermal expansion mismatch between zirconia and veneer on the crack behavior were evaluated. The crack initiation and propagation were well predicted by the three fracture criteria. For specimens at phase angle of 0, the cracks propagated in the interface; whereas for all the other specimens the cracks kinked into the veneer. Compressive residual stresses in the veneer can improve the toughness of the interface structure. The results suggest that, in zirconia/veneer bilayered structure the veneer is weaker than the interface, which can be used to explain the clinical phenomenon that veneer chipping rate is larger than interface delamination rate. Consequently, a veneer material with larger fracture toughness is needed to decrease the failure rate of all-ceramic restorations. And the coefficient of thermal expansion mismatch of the substrates can be larger to produce larger compressive stresses in the veneer. PMID- 25123436 TI - Assessing microbiological water quality in drinking water distribution systems with disinfectant residual using flow cytometry. AB - Flow cytometry (FCM) as a diagnostic tool for enumeration and characterization of microorganisms is rapidly gaining popularity and is increasingly applied in the water industry. In this study we applied the method to obtain a better understanding of total and intact cell concentrations in three different drinking water distribution systems (one using chlorine and two using chloramines as secondary disinfectants). Chloramine tended to result in lower proportions of intact cells than chlorine over a wider residual range, in agreement with existing knowledge that chloramine suppresses regrowth more efficiently. For chlorinated systems, free chlorine concentrations above 0.5 mg L(-1) were found to be associated with relatively low proportions of intact cells, whereas lower disinfectant levels could result in substantially higher percentages of intact cells. The threshold for chlorinated systems is in good agreement with guidelines from the World Health Organization. The fact that the vast majority of samples failing the regulatory coliform standard also showed elevated proportions of intact cells suggests that this parameter might be useful for evaluating risk of failure. Another interesting parameter for judging the microbiological status of water, the biological regrowth potential, greatly varied among different finished waters providing potential help for investment decisions. For its measurement, a simple method was introduced that can easily be performed by water utilities with FCM capability. PMID- 25123437 TI - Modelling the metabolic shift of polyphosphate-accumulating organisms. AB - Enhanced biological phosphorus removal (EBPR) is one of the most important methods of phosphorus removal in municipal wastewater treatment plants, having been described by different modelling approaches. In this process, the PAOs (polyphosphate accumulating organisms) and GAOs (glycogen accumulating organisms) compete for volatile fatty acids uptake under anaerobic conditions. Recent studies have revealed that the metabolic pathways used by PAOs in order to obtain the energy and the reducing power needed for polyhydroxyalkanoates synthesis could change depending on the amount of polyphosphate stored in the cells. The model presented in this paper extends beyond previously developed metabolic models by including the ability of PAO to change their metabolic pathways according to the content of poly-P available. The processes of the PAO metabolic model were adapted to new formulations enabling the change from P-driven VFA uptake to glycogen-driven VFA uptake using the same process equations. The stoichiometric parameters were changed from a typical PAO coefficient to a typical GAO coefficient depending on the internal poly-P with Monod-type expressions. The model was calibrated and validated with seven experiments under different internal poly-P concentrations, showing the ability to correctly represent the PAO metabolic shift at low poly-P concentrations. The sensitivity and error analysis showed that the model is robust and has the ability to describe satisfactorily the change from one metabolic pathway to the other one, thereby encompassing a wider range of process conditions found in EBPR plants. PMID- 25123438 TI - MiR-7b directly targets DC-STAMP causing suppression of NFATc1 and c-Fos signaling during osteoclast fusion and differentiation. AB - DC-STAMP is a key regulating molecule of osteoclastogenesis and osteoclast precursor (OCP) fusion. Emerging lines of evidence showed that microRNAs play crucial roles in bone metabolism and osteoclast differentiation, but no microRNA has yet been reported to be directly related to OCPs fusion. Through a microarray, we found that the expression of miR-7b in RAW264.7 cells was significantly decreased after induction with M-CSF and RANKL. The overexpression of miR-7b in RAW264.7 cells attenuated the number of TRAP-positive cells number and the formation of multinucleated cells, whereas the inhibition of miR-7b enhanced osteoclastogenesis. Through a dual luciferase reporter assay, we confirmed that miR-7b directly targets DC-STAMP. Other fusogenic molecules, such as CD47, ATP6v0d2, and OC-STAMP, were detected to be down-regulated in accordance with the inhibition of DC-STAMP. Because DC-STAMP also participates in osteoclast differentiation through the ITAM-ITIM network, multiple osteoclast-specific genes in the ITAM-ITIM network were detected to identify how DC-STAMP is involved in this process. The results showed that molecules associated with the ITAM-ITIM network, such as NFATc1 and OSCAR, which are crucial in osteoclastogenesis, were consistently altered due to DC-STAMP inhibition. These findings suggest that miR 7b inhibits osteoclastogenesis and cell-cell fusion by directly targeting DC STAMP. In addition, the inhibition of DC-STAMP and its downstream signals changed the expression of other fusogenic genes and key regulating genes, such as Nfatc1, c-fos, Akt, Irf8, Mapk1, and Traf6. In conclusion, our findings indicate that miR 7b may be a potential therapeutic target for the treatment of osteoclast-related bone disorders. PMID- 25123439 TI - Docosahexaenoic acid intake ameliorates ketamine-induced impairment of spatial cognition and learning ability in ICR mice. AB - Several studies have reported the ketamine-induced cognitive impairment. Docosahexaenoic acid (DHA) supplementation improves cognitive function in human infants and protects against learning impairment in patients with Alzheimer's disease (AD). In this study, we investigated the effect of DHA on ketamine induced impairment of spatial cognition and learning ability in Institute of Cancer Research (ICR) mice. Morris water maze (MWM) was used to assess spatial learning and memory. Gamma-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex were measured using high-performance liquid chromatography (HPLC). The results showed that intraperitoneal injection of ketamine (30mg/kg, twice per day) for 4 weeks led to the decline of spatial cognitive ability in mice, and 420mg/(kgd) DHA supplementation for 6 weeks improved ketamine-induced spatial cognitive impairment to a certain extent. The up-regulation of GABA levels in the hippocampus and prefrontal cortex was related to the improvement in spatial learning. Our results suggested that DHA supplementation would be a promising intervention to improve ketamine-induced spatial memory and cognitive dysfunction, and this effect of DHA might be correlated with the up-regulation of GABA levels. PMID- 25123440 TI - Sleep deprivation impairs spontaneous object-place but not novel-object recognition in rats. AB - Effects of sleep deprivation (SD) on one-trial recognition memory were investigated in rats using either a spontaneous novel-object or object-place recognition test. Rats were allowed to explore a field in which two identical objects were presented. After a delay period, they were placed again in the same field in which either: (1) one of the two objects was replaced by another object (novel-object recognition); or (2) one of the sample objects was moved to a different place (object-place recognition), and their exploration behavior to these objects was analyzed. Four hours SD immediately after the sample phase (early SD group) disrupted object-place recognition but not novel-object recognition, while SD 4-8h after the sample phase (delayed SD group) did not affect either paradigm. The results suggest that sleep selectively promotes the consolidation of hippocampal dependent memory, and that this effect is limited to within 4h after learning. PMID- 25123441 TI - The glossopharyngeal nerve controls epithelial expression of Sprr2a and Krt13 around taste buds in the circumvallate papilla. AB - Tastants reach the tip of taste bud cells through taste pores which are openings in the epithelium. We found Sprr2a is selectively expressed in the upper layer of the epithelium surrounding taste buds in the circumvallate papilla (CV) where the epithelium is organized into taste pores. Sprr2a is a member of a small proline rich protein family, which is suggested to be involved in the restitution/migration phase of epithelial wound healing. The expression of Sprr2a was restricted to the upper layer and largely segregated with Ptch1 expression that is restricted to the basal side of the epithelium around the taste buds. Denervation resulted in the gradual loss of Sprr2a-expressing cells over 10 days similarly to that of taste bud cells which is in contrast to the rapid loss of Ptch1 expression. We also found that denervation caused an increase of Keratin (Krt)13 expression around taste buds that corresponded with the disappearance of Sprr2a and Ptch1 expression. Taste buds were surrounded by Krt13-negative cells in the CV in control mice. However, at 6 days post-denervation, taste buds were tightly surrounded by Krt13-positive cells. During taste bud development, taste bud cells emerged together with Krt13-negtive cells, and Sprr2a expression was increased along with the progress of taste bud development. These results demonstrate that regional gene expression surrounding taste buds is associated with taste bud formation and controlled by the innervating taste nerve. PMID- 25123442 TI - Motor and cognitive impairment in a mouse model of ischemic carotid artery disease. AB - We have recently established a novel mouse model of bilateral common carotid artery gradual occlusion. This model serves as a mimic of severe carotid artery disease with multiple cerebral infarctions induced by cerebrovascular insufficiency. In this study, we examined whether locomotor and cognitive impairment was induced in these mice using a test battery for neurological and cognitive functions. Adult C57BL/6J male mice were subjected to either ameroid constrictor (AC) placement to gradually narrow the bilateral common carotid arteries or to sham surgery. At 28 days post-surgery, locomotor activity was assessed by rotarod and wire hang tests, and cognitive function was assessed using the Y-maze and Morris water maze tests. Rotarod and wire hang tests showed a significantly shorter latency to fall in mice subjected to the placement of ACs compared with sham surgery mice. AC-implanted mice showed significant impairments in working memory on the Y-maze test and in spatial learning and reference memory on the Morris water maze test. Therefore, the current mouse model with AC placement on the bilateral common carotid arteries showed locomotor disability, learning deficits, and memory impairment, which well-replicated the outcomes of patients with ischemic carotid artery disease. This model will be useful for investigating the mechanisms underlying the neurological and cognitive deficits following cerebrovascular insufficiency and for exploring pharmacological interventions for stroke patients with severe carotid artery disease. PMID- 25123443 TI - KB-R7943, an inhibitor of the reverse Na(+)/Ca(2+) exchanger, does not modify secondary pathology in the thalamus following focal cerebral stroke in rats. AB - Remote areas connected to cortical infarcts, such as the thalamus, are affected by stroke due to delayed retrograde degeneration of afferent connections. This is temporally associated with the accumulation of beta-amyloid (Abeta) and calcium. Here we tested a hypothesis that prevention of excessive Ca(2+) influx into the axoplasm via the reverse Na(+)/Ca(2+) exchanger (NCX) would provide axonal protection and eventually lessen the Abeta and calcium load in the thalamus. We found that chronic treatment with a specific inhibitor of the reverse NCX, KB R7943 (30mg/kg once daily, 27 days) after middle cerebral artery occlusion did not prevent atypical secondary pathology in the thalamus or improve functional outcome. The present data do not support a role for reverse NCX activity in the complex pathology within the thalamus after cerebral ischemia. PMID- 25123444 TI - Evaluation of several micro RNA (miRNA) levels in children and adolescents with attention deficit hyperactivity disorder. AB - Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent childhood disorders, although disorders etiology and pathogenesis remains unknown, several theories about ADHD development have been proposed and many researchers believe that it is caused by both genetic and environmental factors. In this study we evaluated miR18a-5p, miR22-3p, miR24-3p, miR106b-5p, miR107, miR125b-5p and miR155a-5p levels in child and adolescent ADHD patients. The research sample consisted a group of 52 ADHD patients, and 52 healthy volunteer controls. There was no significant difference in age and sex between the two groups (p>0.05). miRNA 18a-5p, 22-3p, 24-3p, 106b-5p and 107 levels were statistically significantly decreased in ADHD patients(p<0.05). miRNA 155a-5p levels were increased in patients group (p<0.05). The positive predictive value (PPV) and negative predictive value of miR107 was estimated for the cutoff point of 0.4480. PPV was 70% and NPV was 86.5% for the taken cut off point. There could be a close relationship between levels of circulating miRNAs and ADHD. If we could understand how the signaling pathways arranged by miRNAs, impact on CNS development, function and pathology this can improve our knowledge about ADHD etiology and treatment. PMID- 25123445 TI - The free-exploratory paradigm as a model of trait anxiety in female rats: test retest reliability. AB - The free-exploratory paradigm has been proposed as a model of trait anxiety and as such has been proven stable over time, which is a sine qua non condition for any model proposing to evaluate a personality trait. However this stability has only been shown for male rats. Considering that anxiety disorders are most prevalent in women, it's crucial that females are tested in animal models. With this in mind, the stability over time of female rats in the free-exploratory paradigm was evaluated using a test-retest procedure. The behaviour of drug naive, adult, female, Wistar rats was measured in the free-exploratory apparatus on two occasions two months apart. The following parameters were evaluated: percentage of distance travelled in the novel compartment; number of attempts to enter the novel compartment; percentage of time spent in the novel compartment; and percentage of time rearing in the novel compartment. Subsequently, the intraclass correlation coefficient (ICC) and the kappa index (kappa) were calculated for each of these parameters. The "percentage of time spent in the novel compartment" (ICC=0.727; kappa=0.457), the "percentage of distance travelled in the novel compartment" (ICC=0.680; kappa=0.370), and the "percentage of time rearing in the novel compartment" (ICC=0.648; kappa=0.309) were found to be stable over time. Analysis of these parameters indicated fair to substantial reliability over time in two-month inter-trial interval. Therefore, our results support the idea of the free-exploratory paradigm as an animal model of trait anxiety for female rats. PMID- 25123446 TI - The re-organization of functional brain networks in pharmaco-resistant epileptic patients who respond to VNS. AB - Vagal nerve stimulation (VNS) is a therapeutic add-on treatment for patients with pharmaco-resistant epilepsy. The mechanism of action is still largely unknown. Previous studies have shown that brain network topology during the inter-ictal period in epileptic patients deviates from normal configuration. In the present paper, we investigate the relationship between clinical improvement induced by VNS and alterations in brain network topology. We hypothesize that, as a consequence of the VNS add-on treatment, functional brain network architecture shifts back toward a more efficient configuration in patients responding to VNS. Electroencephalographic (EEG) recordings from ten patients affected by pharmaco resistant epilepsy were analyzed in the classical EEG frequency bands. The phase lag index (PLI) was used to estimate functional connectivity between EEG channels and the minimum spanning tree (MST) was computed in order to characterize VNS induced alterations in network topology in a bias-free way. Our results revealed a clear network re-organization, in terms of MST modification, toward a more integrated architecture in patients responding to the VNS. In particular, the results show a significant interaction effect between benefit from VNS (responders/non-responders) and condition (pre/post VNS implantation) in the theta band. This finding suggests that the positive effect induced by VNS add-on treatment in epileptic patients is related to a clear network re-organization and that this network modification can reveal the long debated mechanism of action of VNS. Therefore, MST analysis could be useful in evaluating and monitoring the efficacy of VNS add-on treatment potentially in both epilepsy and psychiatric diseases. PMID- 25123447 TI - Different effects of cabergoline and bromocriptine on metabolic and cardiovascular risk factors in patients with elevated prolactin levels. AB - Hyperprolactinaemia is suggested to be associated with metabolic and hormonal complications. No previous study has compared the effect of different dopamine agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular risk factors in patients with elevated prolactin levels. The study included eight bromocriptine-resistant women with prolactinoma (group 1) and twelve matched women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids, glucose homeostasis markers and plasma levels of prolactin, insulin-like growth factor-1 (IGF-1) and cardiovascular risk factors were assessed before and after 6 months of therapy. Both treatments normalized plasma prolactin levels. Cabergoline reduced triglycerides, 2-hr post-challenge plasma glucose, the homeostatic model assessment of insulin resistance (HOMA-IR), and circulating levels of IGF-1, free fatty acids (FFA), uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL cholesterol and 25-hydroxyvitamin D. With the exception of a reduction in HOMA IR, bromocriptine treatment produced no significant effect on the investigated biomarkers. Cabergoline was superior to bromocriptine in affecting 2-hr post challenge plasma glucose levels, HOMA-IR, as well as circulating levels of IGF-1, FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25-hydroxyvitamin D. Our results may suggest that cabergoline is superior to bromocriptine when it comes to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients. These findings seem to support previous observations that cabergoline may be a better treatment for patients with elevated prolactin levels than bromocriptine. PMID- 25123448 TI - Prevalence of childbirth fear in an Australian sample of pregnant women. AB - BACKGROUND: Childbirth fear is reported to affect around 20% of women. However reporting on levels of symptom severity vary. Unlike Scandinavian countries, there has been limited focus on childbirth fear in Australia. The aim of this paper is to determine the prevalence of low, moderate, high and severe levels of childbirth fear in a large representative sample of pregnant women drawn from a large randomised controlled trial and identify demographic and obstetric characteristics associated with childbirth fear. METHOD: Using a descriptive cross-sectional design, 1,410 women in their second trimester were recruited from one of three public hospitals in south-east Queensland. Participants were screened for childbirth fear using the Wijma Delivery Expectancy/Experience Questionnaire Version A (WDEQ-A). Associations of demographic and obstetric factors and levels of childbirth fear between nulliparous and multiparous women were investigated. RESULTS: Prevalence of childbirth fear was 24% overall, with 31.5% of nulliparous women reporting high levels of fear (score >= 66 on the WDEQ A) compared to 18% of multiparous women. Childbirth fear was associated with paid employment, parity, and mode of last birth, with higher levels of fear in first time mothers (p < 0.001) and in women who had previously had an operative birth (p < 0.001). CONCLUSION: Prevalence of childbirth fear in Australian women was comparable to international rates. Significant factors associated with childbirth fear were being in paid employment, and obstetric characteristics such as parity and birth mode in the previous pregnancy. First time mothers had higher levels of fear than women who had birthed before. A previous operative birth was fear provoking. Experiencing a previous normal birth was protective of childbirth fear. PMID- 25123449 TI - Bright-white beetle scales optimise multiple scattering of light. AB - Whiteness arises from diffuse and broadband reflection of light typically achieved through optical scattering in randomly structured media. In contrast to structural colour due to coherent scattering, white appearance generally requires a relatively thick system comprising randomly positioned high refractive-index scattering centres. Here, we show that the exceptionally bright white appearance of Cyphochilus and Lepidiota stigma beetles arises from a remarkably optimised anisotropy of intra-scale chitin networks, which act as a dense scattering media. Using time-resolved measurements, we show that light propagating in the scales of the beetles undergoes pronounced multiple scattering that is associated with the lowest transport mean free path reported to date for low-refractive-index systems. Our light transport investigation unveil high level of optimisation that achieves high-brightness white in a thin low-mass-per-unit-area anisotropic disordered nanostructure. PMID- 25123452 TI - Could the Affordable Care Act Medicaid expansion affect otolaryngology-head and neck surgery? PMID- 25123450 TI - Comparison of primary target volumes delineated on four-dimensional CT and 18 F FDG PET/CT of non-small-cell lung cancer. AB - BACKGROUND: To determine the optimal threshold of 18 F-fluorodexyglucose (18 F FDG) positron emission tomography CT (PET/CT) images that generates the best volumetric match to internal gross target volume (IGTV) based on four-dimensional CT (4DCT) images. METHODS: Twenty patients with non-small cell lung cancer (NSCLC) underwent enhanced three-dimensional CT (3DCT) scan followed by enhanced 4DCT scan of the thorax under normal free breathing with the administration of intravenous contrast agents. A total of 100 ml of ioversol was injected intravenously, 2 ml/s for 3DCT and 1 ml/s for 4DCT. Then 18 F-FDG PET/CT scan was performed based on the same positioning parameters (the same immobilization devices and identical position verified by laser localizer as well as skin marks). Gross target volumes (GTVs) of the primary tumor were contoured on the ten phases images of 4DCT to generate IGTV10. GTVPET were determined with eight different threshold using an auto-contouring function. The differences in the position, volume, concordance index (CI) and degree of inclusion (DI) of the targets between GTVPET and IGTV10 were compared. RESULTS: The images from seventeen patients were suitable for further analysis. Significant differences between the centric coordinate positions of GTVPET (excluding GTVPET15%) and IGTV10 were observed only in z axes (P < 0.05). GTVPET15%, GTVPET25% and GTVPET2.0 were not statistically different from IGTV10 (P < 0.05). GTVPET15% approximated closely to IGTV10 with median percentage volume changes of 4.86%. The best CI was between IGTV10 and GTVPET15% (0.57). The best DI of IGTV10 in GTVPET was IGTV10 in GTVPET15% (0.80). CONCLUSION: None of the PET-based contours had both close spatial and volumetric approximation to the 4DCT IGTV10. At present 3D-PET/CT should not be used for IGTV generation. PMID- 25123451 TI - Adjuvant-dependent regulation of interleukin-17 expressing gammadelta T cells and inhibition of Th2 responses in allergic airways disease. AB - BACKGROUND: Th2 immune responses are linked primarily to mild and moderate asthma, while Th17 cells, Interleukin-17A (IL-17) and neutrophilia have been implicated in more severe forms of disease. How Th2-dependent allergic reactions are influenced by Th17 and IL-17-gammadelta T cells is poorly understood. In murine models, under some conditions, IL-17 promotes Th2-biased airway inflammatory responses. However, IL-17-gammadelta T cells have been implicated in the inhibition and resolution of allergic airway inflammation and hyperresponsiveness (AHR). METHODS: We compared airway responses in Balb/c mice sensitized to OVA with (and without) a Th2-skewing aluminum-based adjuvant and the IL-17 skewing, complete Freund's adjuvant (CFA). AHR was measured invasively by flexiVent, while serum OVA-IgE was quantified by an enzyme immunoassay. Airway inflammatory and cytokine profiles, and cellular sources of IL-17 were assessed from bronchoalveolar lavage and/or lungs. The role of gammadelta T cells in these responses was addressed in OVA/CFA sensitized mice using a gammadelta T cell antibody. RESULTS: Following OVA challenge, all mice exhibited mixed eosinophilic/neutrophilic airway inflammatory profiles and elevated serum OVA IgE. Whereas OVA/alum sensitized mice had moderate inflammation and AHR, OVA/CFA sensitized mice had significantly greater inflammation but lacked AHR. This correlated with a shift in IL-17 production from CD4+ to gammadelta T cells. Additionally, OVA/CFA sensitized mice, given a gammadelta TCR stimulatory antibody, showed increased frequencies of IL-17-gammadelta T cells and diminished airway reactivity and eosinophilia. CONCLUSIONS: Thus, the conditions of antigen sensitization influence the profile of cells that produce IL-17, the balance of which may then modulate the airway inflammatory responses, including AHR. The possibility for IL-17-gammadelta T cells to reduce AHR and robust eosinophilic inflammation provides evidence that therapeutic approaches focused on stimulating and increasing airway IL-17-gammadelta T cells may be an effective alternative in treating steroid resistant, severe asthma. PMID- 25123453 TI - High expression of microRNA-130b correlates with poor prognosis of patients with hepatocellular carcinoma. AB - BACKGROUND: Whether microRNA-130b(miR-130b) can serve as a prognostic biomarker of hepatocellular carcinoma (HCC) has not been investigated. In the present study, we investigated the feasibility of miR-130b as a novel prognostic biomarker for HCC. METHODS: We retrospectively investigated 97 patients diagnosed with HCC who underwent routine curative surgery between May 2007 and July 2012. miR-130b expression in HCC tissues and paired normal adjacent liver tissues was measured by reverse transcription and real-time PCR (RT-PCR). Survival curves were plotted using the Kaplan-Meier method and differences in survival rates were analyzed using the log-rank test. RESULTS: miR-130b expression level was significantly higher in HCC tissues compared with normal adjacent liver tissues (P<0.0001). The 5-year overall survival (OS) of high miR-130b expression group was significantly shorter than that of low miR-130b expression group (43.6% vs. 71.5%; P=0.022). Moreover, the 5-year disease-free survival (DFS) of high miR 130b expression group was also significantly shorter than that of low miR-130b expression group (25.9% vs. 63.9%; P=0.012). In a multivariate Cox model, we found that miR-130b expression was an independent prognostic factor for both 5 year OS (hazards ratio [HR] =2.523, 95% confidence interval [CI] =1.024-7.901, P=0.011) and 5-year DFS (HR=4.003, CI=1.578-7.899, P=0.005) in HCC. CONCLUSION: The results indicated that high expression of microRNA-130b was correlated with significant characteristics of patients with HCC, and it might be useful as a novel prognostic biomarker for HCC. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_160. PMID- 25123454 TI - Evidence for functional convergence in genes upregulated by herbivores ingesting plant secondary compounds. AB - BACKGROUND: Nearly 40 years ago, Freeland and Janzen predicted that liver biotransformation enzymes dictated diet selection by herbivores. Despite decades of research on model species and humans, little is known about the biotransformation mechanisms used by mammalian herbivores to metabolize plant secondary compounds (PSCs). We investigated the independent evolution of PSC biotransformation mechanisms by capitalizing on a dramatic diet change event-the dietary inclusion of creosote bush (Larrea tridentata)-that occurred in the recent evolutionary history of two species of woodrats (Neotoma lepida and N. bryanti). RESULTS: By comparing gene expression profiles of two populations of woodrats with evolutionary experience to creosote and one population naive to creosote, we identified genes either induced by a diet containing creosote PSCs or constitutively higher in populations with evolutionary experience of creosote. Although only one detoxification gene (an aldo-keto reductase) was induced by both experienced populations, these populations converged upon functionally equivalent strategies to biotransform the PSCs of creosote bush by constitutively expressing aldehyde and alcohol dehydrogenases, Cytochromes P450s, methyltransferases, glutathione S-transferases and sulfotransferases. The response of the naive woodrat population to creosote bush was indicative of extreme physiological stress. CONCLUSIONS: The hepatic detoxification system of mammals is notoriously complex, with hundreds of known biotransformation enzymes. The comparison herein of woodrat taxa that differ in evolutionary and ecological experience with toxins in creosote bush reveals convergence in the overall strategies used by independent species after a historical shift in diet. In addition, remarkably few genes seemed to be important in this dietary shift. The research lays the requisite groundwork for future studies of specific biotransformation pathways used by woodrats to metabolize the toxins in creosote and the evolution of diet switching in woodrats. On a larger level, this work advances our understanding of the mechanisms used by mammalian herbivores to process toxic diets and illustrates the importance of the selective relationship of PSCs in shaping herbivore diversity. PMID- 25123455 TI - A secure and efficient chaotic map-based authenticated key agreement scheme for telecare medicine information systems. AB - Advancement in network technology provides new ways to utilize telecare medicine information systems (TMIS) for patient care. Although TMIS usually faces various attacks as the services are provided over the public network. Recently, Jiang et al. proposed a chaotic map-based remote user authentication scheme for TMIS. Their scheme has the merits of low cost and session key agreement using Chaos theory. It enhances the security of the system by resisting various attacks. In this paper, we analyze the security of Jiang et al.'s scheme and demonstrate that their scheme is vulnerable to denial of service attack. Moreover, we demonstrate flaws in password change phase of their scheme. Further, our aim is to propose a new chaos map-based anonymous user authentication scheme for TMIS to overcome the weaknesses of Jiang et al.'s scheme, while also retaining the original merits of their scheme. We also show that our scheme is secure against various known attacks including the attacks found in Jiang et al.'s scheme. The proposed scheme is comparable in terms of the communication and computational overheads with Jiang et al.'s scheme and other related existing schemes. Moreover, we demonstrate the validity of the proposed scheme through the BAN (Burrows, Abadi, and Needham) logic. PMID- 25123456 TI - QoS-aware health monitoring system using cloud-based WBANs. AB - Wireless Body Area Networks (WBANs) are amongst the best options for remote health monitoring. However, as standalone systems WBANs have many limitations due to the large amount of processed data, mobility of monitored users, and the network coverage area. Integrating WBANs with cloud computing provides effective solutions to these problems and promotes the performance of WBANs based systems. Accordingly, in this paper we propose a cloud-based real-time remote health monitoring system for tracking the health status of non-hospitalized patients while practicing their daily activities. Compared with existing cloud-based WBAN frameworks, we divide the cloud into local one, that includes the monitored users and local medical staff, and a global one that includes the outer world. The performance of the proposed framework is optimized by reducing congestion, interference, and data delivery delay while supporting users' mobility. Several novel techniques and algorithms are proposed to accomplish our objective. First, the concept of data classification and aggregation is utilized to avoid clogging the network with unnecessary data traffic. Second, a dynamic channel assignment policy is developed to distribute the WBANs associated with the users on the available frequency channels to manage interference. Third, a delay-aware routing metric is proposed to be used by the local cloud in its multi-hop communication to speed up the reporting process of the health-related data. Fourth, the delay aware metric is further utilized by the association protocols used by the WBANs to connect with the local cloud. Finally, the system with all the proposed techniques and algorithms is evaluated using extensive ns-2 simulations. The simulation results show superior performance of the proposed architecture in optimizing the end-to-end delay, handling the increased interference levels, maximizing the network capacity, and tracking user's mobility. PMID- 25123457 TI - Using data envelopment analysis to analyse the efficiency of primary care units. AB - In this paper we analyse the efficiency of primary care centres (PCCs) adopting Information and Communication Technology (ICT) devices, using a new database on primary care centres in the Basque Region in Spain. Using a four-stage Data Envelopment Analysis methodology, we are able to explicitly take into account the role of ICT in affecting the efficiency of primary care centres. We understand that this is the first time that ICT enters into the determination of efficiency of the health sector. The role of exogenous factors is explicitly considered in this analysis and shows that including these variables is not neutral to the efficiency evaluation, but leads to an efficiency indicator that only encompasses the effect of managerial skills. The paper provides some useful policy implications regarding the role of ICT in improving the efficiency of primary care units. PMID- 25123459 TI - [Skin adnexal tumors with follicular differentiation]. AB - Skin adnexal tumors with predominantly follicular differentiation represent a clinicopathological heterogeneous group of neoplasms and are classified according to the cytologically achieved differentiation of the follicular compartment. Given the complex structure of non-neoplastic hair follicles it is not surprising to find varying differentiations in neoplasms and there are overlapping clinicopathological features between the established entities. The use of immunohistochemical staining has only a limited value in the diagnosis of follicular neoplasms. PMID- 25123460 TI - Methodological aspects of in vitro assessment of bio-accessible risk element pool in urban particulate matter. AB - In vitro tests simulating the elements release from inhaled urban particulate matter (PM) with artificial lung fluids (Gamble's and Hatch's solutions) and simulated gastric and pancreatic solutions were applied for an estimation of hazardous element (As, Cd, Cr, Hg, Mn, Ni, Pb and Zn) bio-accessibility in this material. An inductively coupled plasma optical emission spectrometry (ICP-OES) and an inductively coupled plasma mass spectrometry (ICP-MS) were employed for the element determination in extracted solutions. The effect of the extraction agent used, extraction time, sample-to-extractant ratio, sample particle size and/or individual element properties was evaluated. Different patterns of individual elements were observed, comparing Hatch's solution vs. simulated gastric and pancreatic solutions. For Hatch's solution, a decreasing sample-to extractant ratio in a PM size fraction of <0.063 mm resulted in increasing leached contents of all investigated elements. As already proved for other operationally defined extraction procedures, the extractable element portions are affected not only by their mobility in the particulate matter itself but also by the sample preparation procedure. Results of simulated in vitro tests can be applied for the reasonable estimation of bio-accessible element portions in the particulate matter as an alternative method, which, consequently, initiates further examinations including potential in vivo assessments. PMID- 25123458 TI - PPM1D silencing by RNA interference inhibits the proliferation of lung cancer cells. AB - BACKGROUND: PPM1D (protein phosphatase, Mg2+/Mn2+ dependent, 1D) has been reported to be involved in multiple human tumors. This study was designed to investigate the functional role of PPM1D in lung cancer cells. METHODS: Expression levels of PPM1D were analyzed in A549 and H1299 cells by real-time PCR and Western blotting. Lentivirus-mediated short hairpin RNA (shRNA) was used to knock down PPM1D expression in both cell lines. The effects of PPM1D on lung cancer cell growth were investigated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide), colony formation and flow cytometry assays. RESULTS: Knockdown of PPM1D in lung cancer cells resulted in decreased cell proliferation and impaired colony formation ability. Moreover, flow cytometry analysis showed that knockdown of PPM1D arrested cell cycle at the G0/G1 phase. Furthermore, PPM1D silencing downregulated the expression of cyclin B1 in H1299 cells. Therefore, it is reasonable to speculate that the mechanisms by which PPM1D knockdown alleviates cell growth may be partly via the induction of cell cycle arrest due to the suppression of cyclin B1. CONCLUSIONS: These results suggest that PPM1D silencing by RNA interference (RNAi) may be a potential therapeutic approach for the treatment of lung cancer. PMID- 25123461 TI - Oxidative stress and Ca(2+) signals involved on cadmium-induced apoptosis in rat hepatocyte. AB - Cadmium (Cd) is an important industrial and environmental pollutant. In animals, the liver is the major target organ of Cd toxicity. In this study, rat hepatocytes were treated with 2.5~10 MUM Cd for various durations. Studies on nuclear morphology, chromatin condensation, and apoptotic cells demonstrate that Cd concentrations ranging within 2.5~10 MUM induced apoptosis. The early-stage marker of apoptosis, i.e., decreased mitochondrial membrane potential, was observed as early as 1.5 h at 5 MUM Cd. Significant (P < 0.01) reactive oxygen species (ROS) production at 5 MUM Cd and 0.75 h occurred prior to the decrease of the mitochondrial membrane potential, suggesting the involvement of ROS in mitochondrial membrane damage. Glutathione (GSH) level significantly decreased after cell treatment with 5 and 10 MUM Cd after 12 h (P < 0.01). Meanwhile, the intracellular free Ca(2+) concentration ([Ca(2+)] i ) of Cd-exposed cells significantly increased (P < 0.01) at 1.5 h, and pretreatment with the calcium chelator Bapta-AM partially blocked Cd-induced apoptosis. This finding indicated that the elevation of [Ca(2+)] i may play an important role in apoptosis. Overall, these results showed that oxidative stress and Ca(2+) signaling were critical mediators of the Cd-induced apoptosis of rat hepatocytes. PMID- 25123462 TI - Possible correlation of selenoprotein W with inflammation factors in chicken skeletal muscles. AB - The aim of the present study was to investigate the possible correlation of selenoprotein W (SelW) with inflammatory injury induced by dietary selenium (Se) deficiency in chicken. One-day-old male chickens were fed either a commercial diet or a Se-deficient diet for 55 days. Then, the expression levels of SelW messenger RNA (mRNA) and inflammation-related genes (NF-kappaB, TNF-alpha, iNOS, COX-2, and PTGES) in chicken skeletal muscles (wing muscle, pectoral muscle, and thigh muscle) were determined at 15, 25, 35, 45, and 55 days old, respectively. In addition, the correlation between SelW mRNA expression and inflammation related genes were assessed. The results showed that dietary Se deficiency reduced the mRNA expression of SelW in chicken wing, pectorals, and thigh muscles. In contrast, Se deficiency increased the mRNA expression levels of inflammation-related genes in chicken skeletal muscle tissues at different time points. The Pearson's correlation coefficients showed that the mRNA expression levels of inflammation-related genes were significantly negative related to SelW (p < 0.05). These data showed that Se deficiency induced the inflammatory response in chicken skeletal muscle. As one important selenoprotein gene in skeletal muscles, SelW may play a role in the regulation of inflammation reaction in Se-deficiency myopathy. PMID- 25123463 TI - Zinc-binding sites on selected flavonoids. AB - Flavonoids have attracted increased attention due to their broad bioactivities related to health and diseases. Modulating metal homeostasis may play an important role in their bioactivities. Recent studies have suggested that dietary flavonoids may affect zinc homeostasis, uptake, and transport. In this work, the zinc-binding sites on a few selected flavonoids have been investigated by (1)H NMR spectroscopy under physiological relevant pH and the species formed were verified by mass spectrometry. Zinc binding induces distinct changes in the proton resonances on the flavonoid rings, providing useful information to locate the Zn-binding sites. No Zn-binding was observed with flavone which lacks a chelation site. Zinc was found to bind to the 3-hydroxyl-4-keto, catechol, and 5 hydroxyl-4-keto chelation sites of flavonol, 3',4'-dihydroxylflavone and chrysin, respectively. Kaempferol and myricetin chelate zinc at the 3-hydroxyl-4-keto site while rutin binds zinc preferentially at the 5-hydroxyl-4-keto site. However, morin appears to bind zinc at the 1-ether-2-hydroxyl site. PMID- 25123464 TI - Security analysis and improvements of authentication and access control in the Internet of Things. AB - Internet of Things is a ubiquitous concept where physical objects are connected over the internet and are provided with unique identifiers to enable their self identification to other devices and the ability to continuously generate data and transmit it over a network. Hence, the security of the network, data and sensor devices is a paramount concern in the IoT network as it grows very fast in terms of exchanged data and interconnected sensor nodes. This paper analyses the authentication and access control method using in the Internet of Things presented by Jing et al. (Authentication and Access Control in the Internet of Things. In Proceedings of the 2012 32nd International Conference on Distributed Computing Systems Workshops, Macau, China, 18-21 June 2012, pp. 588-592). According to our analysis, Jing et al.'s protocol is costly in the message exchange and the security assessment is not strong enough for such a protocol. Therefore, we propose improvements to the protocol to fill the discovered weakness gaps. The protocol enhancements facilitate many services to the users such as user anonymity, mutual authentication, and secure session key establishment. Finally, the performance and security analysis show that the improved protocol possesses many advantages against popular attacks, and achieves better efficiency at low communication cost. PMID- 25123466 TI - Design and implementation of a RF powering circuit for RFID tags or other batteryless embedded devices. AB - A RF powering circuit used in radio-frequency identification (RFID) tags and other batteryless embedded devices is presented in this paper. The RF powering circuit harvests energy from electromagnetic waves and converts the RF energy to a stable voltage source. Analysis of a NMOS gate-cross connected bridge rectifier is conducted to demonstrate relationship between device sizes and power conversion efficiency (PCE) of the rectifier. A rectifier with 38.54% PCE under normal working conditions is designed. Moreover, a stable voltage regulator with a temperature and voltage optimizing strategy including adoption of a combination resistor is developed, which is able to accommodate a large input range of 4 V to 12 V and be immune to temperature variations. Latch-up prevention and noise isolation methods in layout design are also presented. Designed with the HJTC 0.25 MUm process, this regulator achieves 0.04 mV/ degrees C temperature rejection ratio (TRR) and 2.5 mV/V voltage rejection ratio (VRR). The RF powering circuit is also fabricated in the HJTC 0.25 MUm process. The area of the RF powering circuit is 0.23 * 0.24 mm2. The RF powering circuit is successfully integrated with ISO/IEC 15693-compatible and ISO/IEC 14443-compatible RFID tag chips. PMID- 25123465 TI - Acoustic devices for particle and cell manipulation and sensing. AB - An emerging demand for the precise manipulation of cells and particles for applications in cell biology and analytical chemistry has driven rapid development of ultrasonic manipulation technology. Compared to the other manipulation technologies, such as magnetic tweezing, dielectrophoresis and optical tweezing, ultrasonic manipulation has shown potential in a variety of applications, with its advantages of versatile, inexpensive and easy integration into microfluidic systems, maintenance of cell viability, and generation of sufficient forces to handle particles, cells and their agglomerates. This article briefly reviews current practice and reports our development of various ultrasonic standing wave manipulation devices, including simple devices integrated with high frequency (>20 MHz) ultrasonic transducers for the investigation of biological cells and complex ultrasonic transducer array systems to explore the feasibility of electronically controlled 2-D and 3-D manipulation. Piezoelectric and passive materials, fabrication techniques, characterization methods and possible applications are discussed. The behavior and performance of the devices have been investigated and predicted with computer simulations, and verified experimentally. Issues met during development are highlighted and discussed. To assist long term practical adoption, approaches to low-cost, wafer level batch-production and commercialization potential are also addressed. PMID- 25123467 TI - Implantable impedance plethysmography. AB - We demonstrate by theory, as well as by ex vivo and in vivo measurements that impedance plethysmography, applied extravascularly directly on large arteries, is a viable method for monitoring various cardiovascular parameters, such as blood pressure, with high accuracy. The sensor is designed as an implant to monitor cardiac events and arteriosclerotic progression over the long term. PMID- 25123468 TI - Liquid seal for temperature sensing with fiber-optic refractometers. AB - Liquid sealing is an effective method to convert a fiber-optic refractometer into a simple and highly sensitive temperature sensor. A refractometer based on the thin-core fiber modal interferometer is sealed in a capillary tube filled with Cargille oil. Due to the thermo-optic effect of the sealing liquid, the high refractive-index sensitivity refractometer is subsequently sensitive to the ambient temperature. It is found that the liquid-sealed sensor produces a highest sensitivity of -2.30 nm/ degrees C, which is over 250 times higher than its intrinsic sensitivity before sealing and significantly higher than that of a grating-based fiber sensors. The sensing mechanisms, including the incidental temperature-induced strain effect, are analyzed in detail both theoretically and experimentally. The liquid sealing technique is easy and low cost, and makes the sensor robust and insensitive to the surrounding refractive index. It can be applied to other fiber-optic refractometers for temperature sensing. PMID- 25123469 TI - Time- and computation-efficient calibration of MEMS 3D accelerometers and gyroscopes. AB - We propose calibration methods for microelectromechanical system (MEMS) 3D accelerometers and gyroscopes that are efficient in terms of time and computational complexity. The calibration process for both sensors is simple, does not require additional expensive equipment, and can be performed in the field before or between motion measurements. The methods rely on a small number of defined calibration measurements that are used to obtain the values of 12 calibration parameters. This process enables the static compensation of sensor inaccuracies. The values detected by the 3D sensor are interpreted using a generalized 3D sensor model. The model assumes that the values detected by the sensor are equal to the projections of the measured value on the sensor sensitivity axes. Although this finding is trivial for 3D accelerometers, its validity for 3D gyroscopes is not immediately apparent; thus, this paper elaborates on this latter topic. For an example sensor device, calibration parameters were established using calibration measurements of approximately 1.5 min in duration for the 3D accelerometer and 2.5 min in duration for the 3D gyroscope. Correction of each detected 3D value using the established calibration parameters in further measurements requires only nine addition and nine multiplication operations. PMID- 25123470 TI - [Craniocerebral trauma: magnetic resonance imaging of diffuse axonal injury]. AB - CLINICAL/METHODICAL ISSUE: Acceleration-deceleration rotational brain trauma is a common cause of disability or death in young adults and often leads to a focal destruction of axons. The resulting pathology, axonal shear injury is referred to as diffuse axonal injury (DAI). The DAI-associated lesions occur bilaterally, are widely dispersed and have been observed in the surface and deep white matter. They are found near to and far from the impact site. STANDARD RADIOLOGICAL METHODS: When DAI is clinically suspected, magnetic resonance imaging (MRI) is the method of choice for further clarification, especially in patients where cranial computed tomography (CT) is inconspicuous. METHODICAL INNOVATIONS: To investigate the presence of DAI after traumatic brain injury (TBI), a multimodal MRI approach is applied including the common structural and also functional imaging sequences. PERFORMANCE: For structural MRI, fluid-attenuated inversion recovery (FLAIR) weighted and susceptibility contrast imaging (SWI) are the sequences mainly used. The SWI technique is extremely sensitive to blood breakdown products, which appear as small signal voids at three locations, at the gray-white interface, in the corpus callosum and in the brain stem. Functional MRI comprises a group of constantly developing techniques that have great potential in optimal evaluation of the white matter in patients after craniocerebral trauma. These imaging techniques allow the visualization of changes associated with shear injuries, such as functional impairment of axons and decreased blood flow and abnormal metabolic activity of the brain parts affected. ACHIEVEMENTS: The multimodal MRI approach in patients with DAI results in a more detailed and differentiated representation of the underlying pathophysiological changes of the injured nerve tracts and helps to improve the diagnostic and prognostic accuracy of MRI. PRACTICAL RECOMMENDATIONS: When DAI is suspected multimodal MRI should be performed as soon as possible after craniocerebral injury. PMID- 25123471 TI - Internet-based stress management for women with preterm labour--a case-based experience report. AB - Pregnant women with preterm labour (PTL) in pregnancy often experience increased distress and anxieties regarding both the pregnancy and the child's health. The pathogenesis of PTL is, among other causes, related to the stress-associated activation of the maternal-foetal stress system. In spite of these psychobiological associations, only a few research studies have investigated the potential of psychological stress-reducing interventions. The following paper will present an online anxiety and stress management self-help program for pregnant women with PTL. Structure and content of the program will be illustrated by a case-based experience report. L.B., 32 years (G3, P1), was recruited at gestational week 27 while hospitalized for PTL for 3 weeks. She worked independently through the program for 6 weeks and had regular written contact with a therapist. Processing the program had a positive impact on L.B.'s anxiety and stress levels, as well as on her experienced depressive symptoms and bonding to the foetus. As PTL and the risk of PTB are associated with distress, psychological stress-reducing interventions might be beneficial. This study examines the applicability of an online intervention for pregnant women with PTL. The case report illustrates how adequate low-threshold psychological support could be provided to these women. PMID- 25123472 TI - Use of osteoporosis medications among Turkish patients. PMID- 25123473 TI - Correcting for the bias caused by exposure measurement error in epidemiological studies. AB - An important goal of many epidemiological studies is to estimate the magnitude of association between an exposure and an outcome. Exposure measurement error causes bias in such estimates of association and can be substantial. In this article, we describe the problem of exposure measurement error and its effects. We show how a simple hand calculation, in conjunction with validation study data and a calibration equation, can be used to correct estimates for the bias caused by exposure measurement error. Correcting estimates of association for measurement error helps researchers appropriately assess effect size. PMID- 25123476 TI - Tom D. Humphreys II: a pioneer of molecular embryology. PMID- 25123474 TI - SUMO-1 plays crucial roles for spindle organization, chromosome congression, and chromosome segregation during mouse oocyte meiotic maturation. AB - Small ubiquitin-related modifier-1 (SUMO-1)-dependent modifications of many target proteins are involved in a range of intracellular processes. Previous studies reported the localization of SUMO-1 during oocyte meiosis, and that overexpression of Sentrin/SUMO-specific protease 2 (SENP2), a de-SUMOylation protease, altered SUMO-modified proteins, and caused defects in metaphase-II spindle organization. In this study, we detailed the consequences of SUMO-1 mediated SUMOylation by either inhibition of SUMO-1 or UBC9 with a specific antibody or their depletion by specific siRNA microinjection. Inhibition or depletion of SUMO-1 or UBC9 in germinal vesicle (GV)-stage oocytes decreased the rates of germinal vesicle breakdown and first polar body (PB1) extrusion; caused defective spindle organization and misaligned chromosomes; and led to aneuploidy in matured oocytes. Stage-specific antibody injections suggested that SUMO-1 functions before anaphase I during PB1 extrusion. Further experiments indicated that the localization of gamma-tubulin was disordered after SUMO-1 inhibition, and that SUMO-1 depletion disrupted kinetochore-microtubule attachment at metaphase I. Moreover, SUMO-1 inhibition resulted in less-condensed chromosomes, altered localization of REC8 and securin, and reduced BUBR1 accumulation at the centromere. On the other hand, overexpression of SUMO-1 in GV-stage oocytes had no significant effect on oocyte maturation. In conclusion, our results implied that SUMO-1 plays crucial roles during oocyte meiotic maturation, specifically involving spindle assembly and chromosome behavior, by regulating kinetochore microtubule attachment and the localization of gamma-tubulin, BUBR1, REC8, and securin. PMID- 25123478 TI - Noninvasive continuous positive airway pressure delivered using a pediatric helmet in dogs recovering from general anesthesia. AB - OBJECTIVE: To evaluate the feasibility and efficacy of noninvasive continuous positive airway pressure (CPAP) administered with a pediatric helmet in healthy dogs recovering from general anesthesia. DESIGN: Randomized, cross-over, clinical study. SETTING: University teaching hospital. ANIMALS: Fifteen healthy female, client-owned dogs recovering from general anesthesia following elective ovariohysterectomy. INTERVENTIONS: All dogs received the same standardized anesthetic protocol (acepromazine, morphine, propofol, and isoflurane in oxygen). After extubation, a pediatric helmet was placed on all dogs and connected to a venturi valve supplied with medical air. In all patients, the gas flow was set to 50 L/minute and the FiO2 to 0.21. Dogs received the following sequence of treatments, each lasting 20 minutes: 0 CPAP (pre-CPAP), CPAP of 5 cm H2 O (CPAP), and again 0 CPAP (post-CPAP). MEASUREMENTS AND MAIN RESULTS: During the entire study, the following data were collected: pressure and FiO2 inside the helmet, mean arterial pressure, respiratory rate, heart rate, sedation score (0 = awake, 10 = deep sedation), and tolerance to the helmet (0 = excellent, 4 = poor). At the end of each phase, an arterial blood sample was sampled. As compared with the pre-CPAP and the post-CPAP periods, during the CPAP period, the PaCO2 , alveolar arterial oxygen gradient (P[A-a]O2 ), and respiratory rate significantly decreased. The PaO2 was higher at CPAP (105.6 +/- 4.0 mm Hg) compared with pre CPAP (80.6 +/- 6.9 mm Hg) and post-CPAP (86.7 +/- 5.8 mm Hg). Tolerance and sedation scores during the CPAP period were not different from those in the pre CPAP and post-CPAP periods. CONCLUSIONS: Noninvasive CPAP applied through a helmet is a feasible and effective supportive technique in dogs recovering from general anesthesia. PMID- 25123479 TI - Laparoscopic common bile duct exploration. AB - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is a safe and effective single-stage treatment for choledocholithiasis in the elective setting. The outcomes after LCBDE in the emergency setting are unknown. The aim of this study was to compare the outcomes following elective and emergency LCBDE for choledocholithiasis. METHODS: Details of all patients who underwent LCBDE for choledocholithiasis between August 2003 and August 2013 were analysed retrospectively. The primary outcome measure was common bile duct (CBD) stone clearance rate. Secondary outcome measures were conversion rate, morbidity, mortality and length of hospital stay. RESULTS: Some 215 consecutive patients (57 male; median age 65 (range 14-92) years) underwent LCBDE. Some 121 procedures were performed electively and 94 as an emergency. Forty-five patients (48 per cent) presented with obstructive jaundice or cholangitis in the emergency LCBDE group compared with 15 (12.4 per cent) in the elective group (P < 0.001). The CBD stone clearance rate was similarly high in both groups (96 versus 96.7 per cent respectively; P = 0.557). There were no significant differences in conversion rate (6 versus 4.1 per cent), morbidity (5 versus 6.6 per cent), mortality (2 versus 0 per cent) or median length of stay (3 days) between groups. Two patients died, both following emergency LCBDE. CONCLUSION: LCBDE can be performed safely and effectively in both elective and emergency settings. PMID- 25123480 TI - A terminal 3p26.3 deletion is not associated with dysmorphic features and intellectual disability in a four-generation family. AB - Terminal deletions of the distal part of the short arm of chromosome 3 cause a wide range of phenotypes from normal to dysmorphic including microcephaly, developmental delay and intellectual disability. We studied the clinical consequences of a terminal deletion of the short arm of chromosome 3 in four generations of a family. The index patient is a14-month-old boy with microcephaly, corpus callosum dysgenesis, and minor dysmorphic features. Single Nucleotide Polymorphism (SNP) array analysis detected a duplication on the long arm of chromosome 6. His apparently healthy mother carries the same 6q duplication, but as an unexpected finding a terminal deletion of 2.9 Mb of the short arm of chromosome 3 was observed. Further co-segregation analysis in the family for the chromosome 3 deletion showed that with the exception of the sister of the index who has autism, speech delay, and learning problems, family members in four generations of this family are carrier of this 3p deletion and apparently healthy. To our knowledge, this is the first report of a study of this terminal 3p deletion in four generations. In this report, we review the literature on terminal 3p deletions and discuss the importance of molecular testing and reporting of copy number variants to achieve accurate genetic counseling in prenatal and postnatal screening. PMID- 25123482 TI - Ultrafast optical control of orbital and spin dynamics in a solid-state defect. AB - Atom-scale defects in semiconductors are promising building blocks for quantum devices, but our understanding of their material-dependent electronic structure, optical interactions, and dissipation mechanisms is lacking. Using picosecond resonant pulses of light, we study the coherent orbital and spin dynamics of a single nitrogen-vacancy center in diamond over time scales spanning six orders of magnitude. We develop a time-domain quantum tomography technique to precisely map the defect's excited-state Hamiltonian and exploit the excited-state dynamics to control its ground-state spin with optical pulses alone. These techniques generalize to other optically addressable nanoscale spin systems and serve as powerful tools to characterize and control spin qubits for future applications in quantum technology. PMID- 25123481 TI - Structural biology. Crystal structure of a CRISPR RNA-guided surveillance complex bound to a ssDNA target. AB - In prokaryotes, RNA derived from type I and type III CRISPR loci direct large ribonucleoprotein complexes to destroy invading bacteriophage and plasmids. In Escherichia coli, this 405-kilodalton complex is called Cascade. We report the crystal structure of Cascade bound to a single-stranded DNA (ssDNA) target at a resolution of 3.03 angstroms. The structure reveals that the CRISPR RNA and target strands do not form a double helix but instead adopt an underwound ribbon like structure. This noncanonical structure is facilitated by rotation of every sixth nucleotide out of the RNA-DNA hybrid and is stabilized by the highly interlocked organization of protein subunits. These studies provide insight into both the assembly and the activity of this complex and suggest a mechanism to enforce fidelity of target binding. PMID- 25123483 TI - Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of germline DNA. AB - Duchenne muscular dystrophy (DMD) is an inherited X-linked disease caused by mutations in the gene encoding dystrophin, a protein required for muscle fiber integrity. DMD is characterized by progressive muscle weakness and a shortened life span, and there is no effective treatment. We used clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)-mediated genome editing to correct the dystrophin gene (Dmd) mutation in the germ line of mdx mice, a model for DMD, and then monitored muscle structure and function. Genome editing produced genetically mosaic animals containing 2 to 100% correction of the Dmd gene. The degree of muscle phenotypic rescue in mosaic mice exceeded the efficiency of gene correction, likely reflecting an advantage of the corrected cells and their contribution to regenerating muscle. With the anticipated technological advances that will facilitate genome editing of postnatal somatic cells, this strategy may one day allow correction of disease-causing mutations in the muscle tissue of patients with DMD. PMID- 25123485 TI - Glaciers. Attribution of global glacier mass loss to anthropogenic and natural causes. AB - The ongoing global glacier retreat is affecting human societies by causing sea level rise, changing seasonal water availability, and increasing geohazards. Melting glaciers are an icon of anthropogenic climate change. However, glacier response times are typically decades or longer, which implies that the present day glacier retreat is a mixed response to past and current natural climate variability and current anthropogenic forcing. Here we show that only 25 +/- 35% of the global glacier mass loss during the period from 1851 to 2010 is attributable to anthropogenic causes. Nevertheless, the anthropogenic signal is detectable with high confidence in glacier mass balance observations during 1991 to 2010, and the anthropogenic fraction of global glacier mass loss during that period has increased to 69 +/- 24%. PMID- 25123484 TI - A memory of errors in sensorimotor learning. AB - The current view of motor learning suggests that when we revisit a task, the brain recalls the motor commands it previously learned. In this view, motor memory is a memory of motor commands, acquired through trial-and-error and reinforcement. Here we show that the brain controls how much it is willing to learn from the current error through a principled mechanism that depends on the history of past errors. This suggests that the brain stores a previously unknown form of memory, a memory of errors. A mathematical formulation of this idea provides insights into a host of puzzling experimental data, including savings and meta-learning, demonstrating that when we are better at a motor task, it is partly because the brain recognizes the errors it experienced before. PMID- 25123486 TI - Isolation and characterization of microsatellite loci for the blackstripe topminnow Fundulus notatus and their variability in two closely related species. AB - A total of 17 polymorphic microsatellite loci were isolated from the blackstripe topminnow Fundulus notatus. In a sample of 29 individuals, these loci were found to possess two to 19 alleles with expected heterozygosity values ranging from 0.212 to 0.919 and all but one of the loci conformed to Hardy-Weinberg equilibrium expectations. Many of these loci were polymorphic in the closely related species Fundulus olivaceus and Fundulus euryzonus providing a set of markers that should prove useful in future ecological and evolutionary studies of members of this species complex. PMID- 25123487 TI - Occupational injuries in Ohio wood product manufacturing: a descriptive analysis with emphasis on saw-related injuries and associated causes. AB - BACKGROUND: Stationary sawing machinery is often a basic tool in the wood product manufacturing industry and was the source for over 2,500 injury/illness events that resulted in days away from work in 2010. METHODS: We examined 9 years of workers' compensation claims for the state of Ohio in wood product manufacturing with specific attention to saw-related claims. For the study period, 8,547 claims were evaluated; from this group, 716 saw-related cases were examined. RESULTS: The sawmills and wood preservation sub-sector experienced a 71% reduction in average incidence rate and an 87% reduction in average lost-time incidence rate from 2001 to 2009. The top three injury category descriptions for lost-time incidents within saw-related claims were fracture (35.8%), open wounds (29.6%), and amputation (14.8%). CONCLUSIONS: For saw-related injuries, preventing blade contact remains important but securing the work piece to prevent kickback is also important. PMID- 25123488 TI - Generalised hyperpigmentation caused by ectopic adrenocorticotropic hormone syndrome with recurrent thymic neuroendocrine carcinoma. AB - Ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of generalised hyperpigmentation. The clinical features are due to the excessive ectopic secretion of adenocorticotropin by diverse neuroendocrine or non endocrine tumours. Here, we describe a rare case of ectopic ACTH syndrome developing from recurring thymic neuroendocrine carcinoma, which first presented as generalised hyperpigmentation. PMID- 25123489 TI - Minimal benefit of earlier-than-recommended repeat colonoscopy among US Medicare enrollees following a negative colonoscopy. AB - BACKGROUND: A large proportion of US Medicare beneficiaries undergo earlier-than recommended follow-up colonoscopies after negative screening colonoscopy. Such practice entails substantial cost and added risk. AIMS: To compare the risk of colorectal cancer (CRC) associated with varying follow-up colonoscopy intervals following a negative colonoscopy, and to determine whether the potential benefit of a shorter colonoscopy follow-up interval would differ by gender. METHODS: We conducted a weighted cohort study using the Surveillance, Epidemiology and End Results-Medicare linked database (1991-2006) among 932,370 Medicare enrollees who are representative of the entire US elderly population. We compared the cumulative incidence of CRC among patients who underwent follow-up colonoscopies at different intervals following a negative colonoscopy. The primary outcome was incident CRC. RESULTS: The eligible study cohort (n = 480,864) included 106,924 patients who underwent >=1 colonoscopy. Men were more likely to require polypectomy during their initial colonoscopy than women. Compared to the recommended 9-10 year follow-up colonoscopy interval, an interval of 5-6 years was associated with the largest CRC cumulative risk reduction [i.e. 0.17% (95% CI: 0.009-0.32%)]. The magnitude of risk reduction associated with shorter colonoscopy follow-up intervals was not significantly different between men and women. CONCLUSIONS: Among elderly individuals who undergo a negative colonoscopy, the magnitude of reduction in the cumulative CRC risk afforded by earlier-than recommended follow-up colonoscopy is quite small, and probably cannot justify the risk and cost of increased colonoscopy frequency. In addition, there are insufficient differences between men and women to warrant gender-specific recommendations. PMID- 25123490 TI - Up-down asymmetry in vertical induced motion and optokinetic nystagmus. AB - We investigated the effects of pursuit effort against the optokinetic nystagmus (OKN) on induced motion (IM) by measuring vertical IM and eye movements. Participants viewed an inducing stimulus (a random dot pattern) moving either upward or downward at the velocity of 10 or 40 degrees /s. A horizontally moving target (a single dot) was then presented within the inducing stimulus. Participants were asked to pursue the target and report the perceived slant of the target motion path by using a joystick. The results showed that IM magnitude was larger with an upward stimulation than with a downward stimulation. IM magnitude was also larger at 40 degrees /s than at 10 degrees /s. The results of eye movements prior to the target presentation showed that OKN was elicited more effectively with an upward stimulation than with a downward stimulation and at 40 degrees /s than at 10 degrees /s. OKN was markedly reduced when the target was presented within the inducing stimulus. These results support the oculomotor theory that IM magnitude reflects pursuit effort against OKN in response to an inducing stimulus. PMID- 25123491 TI - Stability and binding interaction of bilirubin on a gold nano-surface: steady state fluorescence and FT-IR investigation. AB - A gold nanoparticle exhibits strong absorption and emission due to its unique physical geometry and surface plasmon resonance phenomena. A further modification with organic molecules makes it more appropriate for biological applications. The current manuscript illustrated the optical behavior and stability of bilirubin (BR) coated gold (AuBR) nanoparticles, using BR itself as a reducing agent. In addition, FT-IR and steady state fluorescence measurements were performed to illustrate the binding interaction of BR with the Au(III) ion and the nanoparticles. BR showed a strong affinity towards Au(III) and the measured binding constant was ~4.3 * 10(5) M(-1). It caused reduction of the Au(III) ion and rendered the formation of cubic face centered AuBR nanoparticles, which were ~20 nm in diameter. The particles were stabilized as BR was bound to the gold nanoparticle surface, which was confirmed by FT-IR measurement. An intense carboxyl C=O stretching vibration at 1695 cm(-1) was observed for the BR powder but was absent for the AuBR nanoparticles. However, two weak bands at ~1563 and 1391 cm(-1), presumably due to the asymmetric and symmetric stretching vibrations of the carboxylate form (COO(-)), were found for the AuBR nanoparticles. A stretching vibration of lactam C[double bond, length as m-dash]O appeared at 1645 cm(-1) for BR and the band was shifted to 1647 cm(-1) for the AuBR nanoparticles. The stretching modes of pyrrole N-H and lactam N-H were detected at 3406 cm(-1) and 3267 cm(-1), respectively, for BR. However, the pyrrole N-H band shifted to 3446 cm(-1) and became broader for the AuBR nanoparticles. The observed blue shift in the lactam C[double bond, length as m-dash]O and N-H vibrations of the AuBR nanoparticles indicated a weakening/absence of internal hydrogen bonds between the carboxyl groups and the four N-H bonds in the BR moiety. The binding of BR to the surface provides great stability to the nanoparticles, which remained monodispersed in the large pH range (pH 4 to 12) for more than a month. However, under acidic pH conditions the particles associated to form bigger particles and the plasmon resonance band shifted as they grew; the plasmon resonance band shifted from 525 nm (at pH 7.0) to 555 nm (at pH 3.0). The particles also remained stable in the presence of a higher concentration of salt (KCl and NaCl) in the dispersing media. PMID- 25123492 TI - Effects of small airway dysfunction on the clinical expression of asthma: a focus on asthma symptoms and bronchial hyper-responsiveness. AB - BACKGROUND: The small airways are an important site of inflammation in asthma. However, the relation between small airway dysfunction and clinical expression of asthma has hardly been studied. AIM: To investigate the association of small and large airway dysfunction with asthma symptoms and bronchial hyper-responsiveness (BHR). METHODS: Fifty-eight patients with asthma were characterized with spirometry, body plethysmography, impulse oscillometry, alveolar and bronchial exhaled nitric oxide, and a methacholine provocation. Symptoms of nocturnal asthma, exercise-related symptoms, BHR symptoms, and respiratory symptoms were assessed with the Asthma Control Questionnaire and Bronchial Hyper-responsiveness Questionnaire. Perception of dyspnea was rated with the Borg score during the provocation test. RESULTS: Small and large airway dysfunction did not associate with higher scores for nocturnal, exercise-related, or BHR symptoms. Only higher scores on wheezing were significantly associated with higher values of difference between R5 and R20 (R5-R20) (r = 0.367, P < 0.01) and AX (r = 0.354, P < 0.01). Lower FEF25-75% (P = 0.024) and higher R5-R20 (P = 0.003) values were independently associated with more severe BHR to methacholine, but not FEV1 or R20 values. The increase in dyspnea during the methacholine provocation was strongly and independently correlated with the decrease in FEV1 and reactance of the respiratory system at 5 Hertz. CONCLUSION: Small and large airway dysfunction poorly associate with asthma symptoms in our patients. However, deteriorations in small airway dysfunction are strongly related to an increase in dyspnea during bronchial provocation with methacholine. Small airway dysfunction contributes also independently to the clinical expression of asthma, as reflected by the severity of BHR. PMID- 25123493 TI - Total syntheses of lycoposerramine-V and 5-epi-lycoposerramine-V. AB - Enantioselective total syntheses of lycopodium alkaloids lycoposerramine-V and 5 epi-lycoposerramine-V have been accomplished. Features of the newly established total synthesis include: 1) introduction of the first chiral center with a scalable desymmetrization reaction of an meso-anhydride; 2) chemoselective functionalization of a bis-Weinreb-amide with Grignard addition; and 3) construction of the multifunctionalized cyclohexanone with a stereoselective intramolecular Michael addition. PMID- 25123496 TI - Binary-metal perovskites toward high-performance planar-heterojunction hybrid solar cells. AB - A simple, low temperature solution process for Pb/Sn binary-metal perovskite planar-heterojunction solar cells is demonstrated. Sn inclusion substantially influences the band-gap, crystallization kinetics, and thin-film formation leading to a broadened light absorption and enhanced film coverage on ITO/PEDOT:PSS. As a result, the optimized device shows a PCE exceeding 10%, which is the best result for binary-metal perovskite solar cells so far. PMID- 25123497 TI - Assembly of Na3V2(PO4)3 nanoparticles confined in a one-dimensional carbon sheath for enhanced sodium-ion cathode properties. AB - Structural and morphological control is an effective approach for improvement of electrochemical properties in rechargeable batteries. One-dimensionally assembled structure composed of NASICON-type Na3 V2 (PO4 )3 nanoparticles were fabricated through an electrospinning method to meet the requirements for the development of efficient electrode materials in Na-ion batteries. High-temperature treatment of electrospun precursor fibers under an argon flow provides a nonwoven fabric of nanowires comprising crystallographically oriented nanoparticles of NASICON-type Na3 V2 (PO4 )3 within a carbon sheath. The mesostructure comprising NASICON-type Na3 V2 (PO4 )3 and carbon give a short sodium-ion transport pass and an efficient electron conduction pass. Electrochemical properties of NASICON-type Na3 V2 (PO4 )3 are improved on the basis of one-dimensional nanostructures designed in the present study. PMID- 25123494 TI - The effect of hazelnut roasted skin from different cultivars on the quality attributes, polyphenol content and texture of fresh egg pasta. AB - BACKGROUND: Hazelnut skin is the perisperm of the hazelnut kernel. It is separated from the kernel during the roasting process and is normally discarded. Recent studies have reported that hazelnut skin is a rich source of dietary fibre as well as of natural antioxidants owing to the presence of phenolic compounds. The aim of this study was to assess the use of hazelnut skins obtained from different cultivars for enhancing the nutritional value of fresh egg pasta. RESULTS: Skins obtained from roasted hazelnuts of four different varieties were used at three concentrations as a flour replacement in fresh egg pasta. Hazelnut skin concentration significantly influenced all evaluated physicochemical parameters as well as consumers' appreciation for the pasta, but significant differences were also observed between the four varieties. Although pasta produced with 10 and 15% hazelnut skin displayed the highest content of polyphenolic compounds and antioxidant activity in vitro, pasta containing 5% Tombul hazelnut skin showed maximum consumer preference. CONCLUSION: The results obtained in the present study highlighted that it is possible to use hazelnut skin in fresh pasta production to obtain a fortified food with high fibre content and antioxidant activity. The characteristics of the resulting pasta were strictly correlated with the hazelnut variety used for skin production and, of course, with the percentage of skin that was added. PMID- 25123495 TI - Real-time assessment of possible electromagnetic-field-induced changes in protein conformation and thermal stability. AB - Previous studies on possible interactions of radiofrequency electromagnetic fields (RF EMFs) with proteins have suggested that RF EMFs might affect protein structure and folding kinetics. In this study, the isolated thermosensor protein GrpE of the Hsp70 chaperone system of Escherichia coli was exposed to EMFs of various frequencies and field strengths under strictly controlled conditions. Circular dichroism spectroscopy was used to monitor possible structural changes. Simultaneously, temperature was recorded at each point of observation. The coiled coil part of GrpE has been reported to undergo a well-defined and fully reversible folding/unfolding transition, thus facilitating the differentiation between thermal and non-thermal effects of RF EMFs. Any direct effect of EMF on the conformation and/or stability would result in a shift of the conformational equilibrium of the protein at a given temperature. Possible immediate (t <= 0.1 s) and delayed (t >= 30 s) effects of RF EMFs were investigated with sinusoidal signals of 0.1, 1.0, and 1.9 GHz at various field strengths up to 5.0 kV/m and with GSM signals at 0.3 kV/m in the protein solution. Taking the overall uncertainty of the experimental system into account, possible RF EMF-induced shifts in the conformational equilibrium of less than 1% of its total range might have been detected. The results obtained with the different experimental protocols indicate, however, that the conformational equilibrium of GrpE is insensitive to electromagnetic fields in the tested range of frequency and field strength. PMID- 25123498 TI - Absorbing phase transitions and dynamic freezing in running active matter systems. AB - We examine a two-dimensional system of sterically repulsive interacting disks where each particle runs in a random direction. This system is equivalent to a run-and-tumble dynamics system in the limit where the run time is infinite. At low densities, we find a strongly fluctuating state composed of transient clusters. Above a critical density that is well below the density at which non active particles would crystallize, the system can organize into a drifting quiescent or frozen state where the fluctuations are lost and large crystallites form surrounded by a small density of individual particles. Although all the particles are still moving, their paths form closed orbits. The average transient time to organize into the quiescent state diverges as a power law upon approaching the critical density from above. We compare our results to the random organization observed for periodically sheared systems that can undergo an absorbing transition from a fluctuating state to a dynamical non-fluctuating state. In the random organization studies, the system organizes to a state in which the particles no longer interact; in contrast, we find that the randomly running active matter organizes to a strongly interacting dynamically jammed state. We show that the transition to the frozen state is robust against a certain range of stochastic fluctuations. We also examine the effects of adding a small number of pinned particles to the system and find that the transition to the frozen state shifts to significantly lower densities and arises via the nucleation of faceted crystals centered at the obstacles. PMID- 25123503 TI - Electronic property modification of single-walled carbon nanotubes by encapsulation of sulfur-terminated graphene nanoribbons. AB - The use of carbon nanotubes (CNTs) as cylindrical reactor vessels has become a viable means for synthesizing graphene nanoribbons (GNRs). While previous studies demonstrated that the size and edge structure of the as-produced GNRs are strongly dependent on the diameter of the tubes and the nature of the precursor, the atomic interactions between GNRs and surrounding CNTs and their effect on the electronic properties of the overall system are not well understood. Here, it is shown that the functional terminations of the GNR edges can have a strong influence on the electronic structure of the system. Analysis of SWCNTs before and after the insertion of sulfur-terminated GNRs suggests a metallization of the majority of semiconducting SWCNTs. This is indicated by changes in the radial breathing modes and the D and G band Raman features, as well as UV-vis-NIR absorption spectra. The variation in resonance conditions of the nanotubes following GNR insertion make direct (n,m) assignment by Raman spectroscopy difficult. Thus, density functional theory calculations of representative GNR/SWCNT systems are performed. The results confirm significant changes in the band structure, including the development of a metallic state in the semiconducting SWCNTs due to sulfur/tube interactions. The GNR-induced metallization of semiconducting SWCNTs may offer a means of controlling the electronic properties of bulk CNT samples and eliminate the need for a physical separation of semiconducting and metallic tubes. PMID- 25123499 TI - Implications of a suspicious afirma test result in thyroid fine-needle aspiration cytology: an institutional experience. AB - BACKGROUND: Fine-needle aspiration (FNA) biopsy is the most frequently used method for thyroid nodule evaluation. However, up to 30% of cases are considered indeterminate. Surgery is typically recommended for these cases, but up to two thirds of indeterminate cases are found to be benign. The Afirma test is used for the preoperative classification of thyroid nodules with indeterminate cytology. This study reviews the authors' institutional experience with Afirma. METHODS: A cohort of 132 cases of thyroid FNA with Afirma testing was selected from the study files and relevant information was recorded and analyzed. At the study institution, Afirma is mainly performed on atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) cases when diagnosed as such on repeat FNA. RESULTS: The cohort included 98 female (74%) and 34 male (26%) patients. Cytology diagnosis was AUS/FLUS in 68 cases (51.5%), follicular neoplasm (FN) in 39 cases (29.5%), and FN with oncocytic features (FNOF) in 25 cases (19.0%). Of the FNOF cases with suspicious Afirma findings, 2 (15%) were malignant and 11 (85%) were benign. Of the FN cases with suspicious Afirma findings, 9 (53%) were malignant and 8 (47%) were benign. Of the AUS/FLUS cases with suspicious Afirma findings, 10 (63%) were malignant and 6 (37%) were benign. CONCLUSIONS: The Afirma classifier is a useful tool to aid in the distinction of cytologically indeterminate nodules. Performing Afirma in cases diagnosed as AUS/FLUS on repeat FNA would increase the positive predictive value, thereby minimizing the number of benign cases referred to surgery. Results of the Afirma test could be limited in cases diagnosed as FNOF. PMID- 25123504 TI - The role of hepatic artery lymph node in pancreatic adenocarcinoma: prognostic factor or a selection criterion for surgery. AB - BACKGROUND: Hepatic artery lymph node (HALN) metastasis in pancreatic adenocarcinoma reportedly confers a survival disadvantage. This has led some authors to propose it as an indicator against pancreaticoduodenectomy (PD). METHODS: Consecutive patients who underwent PD during 2002-2012 were identified from the University of Louisville prospective hepatopancreaticobiliary database. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan Meier analysis. The log-rank test and multivariate Cox proportional hazards regression were used in further analyses. RESULTS: A total of 420 patients underwent PD during the period of study, of whom 197 had lymph node (LN) metastasis. Among these, 41 (20.8%) patients had disease-positive HALNs. The HALN was the only site of LN metastasis in only three of the 247 patients (1.2%). Median follow-up was 18.5 months (interquartile range: 4.1-28.2 months). Median OS and DFS were 22.7 months [95% confidence interval (CI) 19.0-26.3] and 12.6 months (95% CI 10.2-15.2). There was no significant difference in median OS between HALN-positive patients (18.4 months, 95% CI 12.3-24.0) and HALN-negative patients (19.7 months, 95% CI 16.7-22.6) (P = 0.659). On multivariate analysis, the hazard ratio (HR) of death was highest among patients with an LN ratio of >0.2 (HR 1.2, 95% CI 1.1-1.29; P = 0.012) followed by those with poorly differentiated histology (HR 1.09, 95% CI 1.04-1.11; P = 0.029). CONCLUSIONS: In pancreatic adenocarcinoma patients with LN disease, survival after PD is comparable regardless of HALN status. Therefore, HALN-positive disease should not preclude the performance of PD. PMID- 25123505 TI - Expression of TNF-alpha and CD44 is implicated in poor prognosis, cancer cell invasion, metastasis and resistance to the sunitinib treatment in clear cell renal cell carcinomas. AB - Tumor necrosis factor-alpha (TNF-alpha) is involved in epithelial-mesenchymal transition (EMT) and expression of CD44, a cancer stem cell marker, in several cancers. This study was performed to clarify the significance of TNF-alpha and CD44 in clear cell renal cell carcinomas (ccRCCs). Expression of TNF-alpha and CD44 was examined by immunohistochemistry in 120 ccRCCs. Involvement of TNF-alpha in EMT and induction of CD44 was analyzed by monitoring expression of EMT-related genes and CD44, and invasion in cultured ccRCC cell lines. TNF-alpha and CD44 were immunolocalized mainly to carcinoma cells of high-grade ccRCCs with positive correlations with primary tumor stage. A positive correlation was also obtained between TNF-alpha and CD44 expression, and co-upregulation of TNF-alpha and CD44 was associated with primary tumor stage, distant metastasis, and poor prognosis. TNF-alpha enhanced migration and invasion of ccRCC cells together with down regulation of E-cadherin expression and up-regulation of matrix metalloproteinase 9 and CD44 expression. TNF-alpha also up-regulated the expression of TNF-alpha itself in ccRCC cells. Among the 25 ccRCC patients treated with sunitinib for metastatic disease, high CD44 expression was associated with poor treatment outcome. Importantly, residual carcinoma cells in the sunitinib-treated metastatic ccRCCs were strongly positive for CD44, and the CD44 expression was significantly higher in the tumors from the sunitinib-treated patients than in those from untreated ones. Our data show that TNF-alpha plays an important role in progression of ccRCCs by inducing EMT and CD44 expression, and suggest that CD44 induced by TNF-alpha may be involved in the resistance to the sunitinib treatment. PMID- 25123506 TI - Safety assessment of jumps in ski racing. AB - The influence of important parameters on the flight trajectory for jumps in downhill World Cup races was investigated. To quantify the impact injury risk at landing, the parameter equivalent landing height (ELH) was introduced, which considered a variable slope inclination during the landing movement. Altogether, 145 runs at four different jumps in World Cup races and trainings were recorded and analyzed. A simulation model was developed to predict the flight phase of the skier. Drag and lift areas were selected by parameter identification to fit the simulation trajectory to the two-dimensional data from the video analysis. The maximum values of the ELH which can be absorbed with muscle force was taken from the study of Minetti et al. for elite female and male ski racers. A sensitivity analysis based on the four jumps showed that ELH is mainly influenced by takeoff angle, takeoff speed, and the steepness of the landing surface. With the help of the developed simulation software, it should be possible to predict the ELH for jumps in advance. In case of an excessive ELH, improvements can be made by changing the takeoff inclination or the approach speed. PMID- 25123507 TI - Adaptation in tunably rugged fitness landscapes: the rough Mount Fuji model. AB - Much of the current theory of adaptation is based on Gillespie's mutational landscape model (MLM), which assumes that the fitness values of genotypes linked by single mutational steps are independent random variables. On the other hand, a growing body of empirical evidence shows that real fitness landscapes, while possessing a considerable amount of ruggedness, are smoother than predicted by the MLM. In the present article we propose and analyze a simple fitness landscape model with tunable ruggedness based on the rough Mount Fuji (RMF) model originally introduced by Aita et al. in the context of protein evolution. We provide a comprehensive collection of results pertaining to the topographical structure of RMF landscapes, including explicit formulas for the expected number of local fitness maxima, the location of the global peak, and the fitness correlation function. The statistics of single and multiple adaptive steps on the RMF landscape are explored mainly through simulations, and the results are compared to the known behavior in the MLM model. Finally, we show that the RMF model can explain the large number of second-step mutations observed on a highly fit first-step background in a recent evolution experiment with a microvirid bacteriophage. PMID- 25123509 TI - Hydrogen sulfide is essential for Schwann cell responses to peripheral nerve injury. AB - Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from substances by three enzymes: cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST). In human tissues, these enzymes are involved in tissue-specific biochemical pathways for H2 S production. For example, CBS and cysteine aminotransferase/MST are present in the brain, but CSE is not. Thus, we examined the expression of H2 S production-related enzymes in peripheral nerves. Here, we found that CSE and MST/cysteine aminotransferase, but not CBS, were present in normal peripheral nerves. In addition, injured sciatic nerves in vivo up-regulated CSE in Schwann cells during Wallerian degeneration (WD); however, CSE was not up-regulated in peripheral axons. Using an ex vivo sciatic nerve explant culture, we found that the inhibition of H2 S production broadly prevented the process of nerve degeneration, including myelin fragmentation, axonal degradation, Schwann cell dedifferentiation, and Schwann cell proliferation in vitro and in vivo. Thus, these results indicate that H2 S signaling is essential for Schwann cell responses to peripheral nerve injury. Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), and 3 mercaptopyruvate sulfur transferase (MST). Here, we found that CSE and MST/CAT were present in normal peripheral nerves. Injured static nerves in vivo up regulated CSE in Schwann cells during Wallerian degeneration, but CSE was not up regulated in peripheral axons. PMID- 25123508 TI - The switch from fermentation to respiration in Saccharomyces cerevisiae is regulated by the Ert1 transcriptional activator/repressor. AB - In the yeast Saccharomyces cerevisiae, fermentation is the major pathway for energy production, even under aerobic conditions. However, when glucose becomes scarce, ethanol produced during fermentation is used as a carbon source, requiring a shift to respiration. This adaptation results in massive reprogramming of gene expression. Increased expression of genes for gluconeogenesis and the glyoxylate cycle is observed upon a shift to ethanol and, conversely, expression of some fermentation genes is reduced. The zinc cluster proteins Cat8, Sip4, and Rds2, as well as Adr1, have been shown to mediate this reprogramming of gene expression. In this study, we have characterized the gene YBR239C encoding a putative zinc cluster protein and it was named ERT1 (ethanol regulated transcription factor 1). ChIP-chip analysis showed that Ert1 binds to a limited number of targets in the presence of glucose. The strongest enrichment was observed at the promoter of PCK1 encoding an important gluconeogenic enzyme. With ethanol as the carbon source, enrichment was observed with many additional genes involved in gluconeogenesis and mitochondrial function. Use of lacZ reporters and quantitative RT-PCR analyses demonstrated that Ert1 regulates expression of its target genes in a manner that is highly redundant with other regulators of gluconeogenesis. Interestingly, in the presence of ethanol, Ert1 is a repressor of PDC1 encoding an important enzyme for fermentation. We also show that Ert1 binds directly to the PCK1 and PDC1 promoters. In summary, Ert1 is a novel factor involved in the regulation of gluconeogenesis as well as a key fermentation gene. PMID- 25123511 TI - Arthroscopy versus arthrocentesis in the management of internal derangement of the temporomandibular joint: a systematic review and meta-analysis. AB - The aim of this study was to assess whether arthroscopy or arthrocentesis is most effective and feasible in the management of internal derangement of the temporomandibular joint (TMJ), specifically in relation to joint movement and pain. A comprehensive electronic search without date or language restrictions was performed in January 2014. Inclusion criteria were the following: study in humans; randomized or quasi-randomized controlled trials (RCTs), controlled clinical trials (CCTs), and retrospective studies; comparison of arthrocentesis and arthroscopy in the treatment of internal derangement. Six publications were included in the review, two RCTs, two CCTs, and two retrospective studies. Two studies showed a low risk of bias and four studies showed a moderate risk of bias. There were statistically significant differences between arthrocentesis and arthroscopy with regard to maximal inter-incisal opening and pain reduction, but no difference between the two groups for postoperative complications. The results of this meta-analysis on the management of internal derangement of the TMJ revealed arthroscopy to have superior efficacy to arthrocentesis in increasing joint movement and decreasing pain. Both arthroscopy and arthrocentesis have comparable postoperative complication rates. However, the current meta-analysis is incomplete due to the paucity of good quality studies in the high-impact, peer reviewed literature; therefore, further better-designed studies are required to address this important question before final conclusions can be drawn as to the true comparative outcomes of TMJ arthrocentesis versus TMJ arthroscopy. PMID- 25123510 TI - Enhancing radiotherapy by lipid nanocapsule-mediated delivery of amphiphilic gold nanoparticles to intracellular membranes. AB - Amphiphilic gold nanoparticles (amph-NPs), composed of gold cores surrounded by an amphiphilic mixed organic ligand shell, are capable of embedding within and traversing lipid membranes. Here we describe a strategy using crosslink stabilized lipid nanocapsules (NCs) as carriers to transport such membrane penetrating particles into tumor cells and promote their transfer to intracellular membranes for enhanced radiotherapy of cancer. We synthesized and characterized interbilayer-crosslinked multilamellar lipid vesicles (ICMVs) carrying amph-NPs embedded in the capsule walls, forming Au-NCs. Confocal and electron microscopies revealed that the intracellular distribution of amph-NPs within melanoma and breast tumor cells following uptake of free particles vs Au NCs was quite distinct and that amph-NPs initially delivered into endosomes by Au NCs transferred over a period of hours to intracellular membranes through tumor cells, with greater intracellular spread in melanoma cells than breast carcinoma cells. Clonogenic assays revealed that Au-NCs enhanced radiotherapeutic killing of melanoma cells. Thus, multilamellar lipid capsules may serve as an effective carrier to deliver amphiphilic gold nanoparticles to tumors, where the membrane penetrating properties of these materials can significantly enhance the efficacy of frontline radiotherapy treatments. PMID- 25123512 TI - Transcriptionist saturation: knowing too much about sensitive health and social data. AB - AIM: The paper describes and interprets the experiences of transcriptionists employed to translate recorded auditory research, medical, court data into text and specifically when the research is sensitive and the audio source material may be traumatic to hear. BACKGROUND: This study highlights the ongoing need for transcriptionists to be recognized in the ethics process as a potentially vulnerable group who need greater support and debriefing when transcribing sensitive health and social data. DESIGN: Qualitative research. METHODS: Telephone interviews were conducted with 12 transcriptionists in Australia and New Zealand during 2012, who had transcribed sensitive material and reported issues with transcribing certain topics. Accuracy and confidentiality were paramount in this work. FINDINGS: Seven participants reported negative emotional and physical effects from transcribing sensitive material On the other hand six participants found the work enjoyable. CONCLUSION: The majority of the transcriptionists did not receive any debriefing after transcribing sensitive material. The participants developed their own strategies to deal with the effects of transcribing sensitive materials such as online support groups, relaxation activities and unofficial debriefing with friends and family. PMID- 25123513 TI - Viewing rate and reproducibility of papillary muscle areas in foetal atrioventricular valves using spatio-temporal image correlation in the rendering mode in congenital heart disease. AB - OBJECTIVE: To assess the viewing rate and reproducibility of areas of the papillary muscles (PMs) of foetal atrioventricular valves using spatio-temporal image correlation (STIC) in the rendering mode in congenital heart disease (CHD). METHODS: We retrospectively reviewed 40 4D-STIC volume datasets from different foetal CHD cases at a gestational age of 18w6d-35w6d. The following papillary muscles (PMs) were assessed: antero-lateral (MPAL) and postero-medial (MPPM) to the mitral valve and antero-superior (MPAS), inferior (MPI) and septal (MPS) to the tricuspid valve. To assess the valve viewing rate, percentages (%) were used. The concordance correlation coefficient (CCC) was used to assess inter-observer reliability. RESULTS: Two independent observers concluded that a complete examination of the PMs was impossible in 11 cases, yielding a viewing rate of 72.5%. The complete examination of the PMs of the tricuspid and mitral valves was possible by both examiners in 33/40 (82.5%) and 32/40 (80.0%) cases, respectively. We observed moderate to good inter-observer reliability with CCCs of 0.95, 0.92, 0.97, 0.96 and 0.97 for MPS, MPI, MPAS, MPAL and MPPM, respectively. CONCLUSION: The viewing rate of PM areas in different CHDs using STIC in the rendering mode was moderate. The inter-observer reproducibility was moderate to good for all PM areas. PMID- 25123514 TI - Can measurement of cervical length, fetal head position and posterior cervical angle be an alternative method to Bishop score in the prediction of successful labor induction? AB - Abstract Aim: The purpose of this study was to evaluate sonographic cervical length, posterior cervical angle and fetal head position in predicting successful induction of labor at term can be an alternative method to Bishop score. Methods: This prospective observational study recruited 223 women with singleton gestations scheduled for induction of labor at 37-42 weeks. Parity, body mass index, Bishop score, fetal head position, cervical angle measurement and cervical length was investigated to predict successful labor induction. Multiple regression analysis was performed to determine the parameters in the prediction of successful vaginal delivery within 24 hours. Results: Forty-five patients were excluded because of cesarean section performed for other reasons than arrest of dilation or fetal head descent (43 fetal distress, 2 cord prolapsus). Remaining 178 patients were divided into two groups according to duration of delivery time. 139 patients delivered within 24 hours were classified as group I, 39 patients delivered after 24 hours were classified as group II. Percentage of multiparity was statistically significantly higher in group I than in group II [59 (42.4%), 9 (23.0%) respectively, p = 0.009]. Cervical length was statistically significantly shorter in group I than in group II [23.1 +/- 7.42 mm, 31.3 +/- 6.83 mm respectively, p < 0.001]. Bishop score was statistically significantly higher in group I than in group II [3 (1-4), 1 (1-4) respectively, p < 0.001]. Posterior cervical angle was statistically significantly higher in group I than in group II [100.1 +/- 17.2, 92.7 +/- 21.4 respectively, p = 0.007]. According to the fetal head position, there was no statistically significant difference in labor duration between the groups (p = 0.787). In the multivariate regression analysis of variables, multiparity, cervical length and Bishop score were statistically significantly predictive in successful labor induction. Conclusion: Multiparity status, cervical length, posterior cervical angle and Bishop score can predict successful labor induction, but fetal head position is not predictive in successful labor induction. PMID- 25123516 TI - The effect of a 25-hour fast during the Day of Atonement on preterm delivery. AB - OBJECTIVE: To determine the effect of the Day of Atonement fast (a 25-hour Jewish fast), on preterm delivery. METHODS: A comprehensive analysis of all deliveries during the Day of Atonement and during the corresponding day a week earlier, between the years 1988 and 2011, was performed. Preterm delivery was defined as delivery before 37 completed weeks of gestation. Data on fasting status was deduced from the ethnicity (as only Jewish parturients fast during the Day of Atonement). Multivariable logistic regression model was used to control for confounders. RESULTS: During the Day of Atonement in the studied period, 744 deliveries took place, out of which 52.1% (n = 388) were of Jewish patients (i.e. fasting group), and 47.9% (n = 357) were of non-Jewish patients. Out these, 6.3% (n = 47) were preterm deliveries. Jewish parturients were at significantly higher risk for preterm delivery during the Day of Atonement (adjusted OR = 2.0; 95% CI, 1.03-3.83; p = 0.041). In the corresponding day, a week before the Day of Atonement, Jewish ethnicity was not found to be a risk factor for preterm delivery (OR = 0.92; 95% CI, 0.50-1.69; p = 0.789). The model controlled for: previous preterm delivery, intrauterine growth restriction and placental abruption. CONCLUSIONS: A 25-hour fast is an independent risk factor for preterm delivery. PMID- 25123517 TI - A comparison between electrical uterine monitor, tocodynamometer and intra uterine pressure catheter for uterine activity in labor. AB - OBJECTIVE: We aimed to evaluate the performance of a non-invasive EMG electrical uterine monitor (EUM) versus tocodynamometry (TOCO) by comparing both to internal uterine pressure catheter (IUPC). STUDY DESIGN: Prospective observational trial. Uterine activity was recorded continuously and simultaneously, in women during active term labor, with TOCO, EUM and IUPC. Uterine activity tracings were analyzed by three blinded physicians. RESULTS: Overall, 385 tracings from 43 women were analyzed. A similar rate of interpretable tracings between physicians was demonstrated for EUM (87%; 95% CI 80.9-92.7%) and IUPC (94.8%; 95% CI 83.4 96.3%), with a significantly lower rate for TOCO (67.5%; 95% CI 59.4-76.8%, p < 0.001). There is a significant difference in the contraction frequency for EUM versus IUPC (0.77 +/- 2.3) compared to TOCO versus IUPC (-3.34 +/- 4.97). There is a high variability between the timing of TOCO contractions as compared to IUPC (4.74 +/- 10.03 seconds), while a gap of 8.46 +/- 4.24 seconds was detected for EUM. The sensitivity, positive predictive value and false positive rate for individual contraction identification by TOCO and EUM are 54.0%, 84.4%, 15.6% and 94.2%, 87.6%, 12.4%, respectively. CONCLUSION: EUM is efficient as IUPC for uterine activity assessment and both techniques are superior in comparison to external tocodynamometry. Our results support the use of non-invasive EMG technology to monitor uterine activity. PMID- 25123518 TI - Brain stem/brain stem occipital bone ratio and the four-line view in nuchal translucency images of fetuses with open spina bifida. AB - Abstract Objective: Brain stem depth/brain stem occipital bone distance (BS/BSOB ratio) and the four-line view, in images obtained for nuchal translucency (NT) screening in fetuses with open spina bifida (OSB). Methods: Single center, retrospective study based on the assessment of NT screening images of fetuses with OSB. A ratio between the BS depth and the BSOB distance was calculated (BS/BSOB ratio) and the four-line view observed, and the sensitivity for a BS/BSOB ratio superior/equal to 1, and for the lack of detection of the four-line view were calculated. Results: There were 17 cases of prenatal diagnosis OSB. In six cases, the suspicion on OSB was raised during NT screening, in six cases, the diagnosis was made before 20 weeks and in five cases during anomaly scan. The BS/BSOB ratio was superior/equal to 1 in all 17 cases, and three lines, were visualized in 15/17 images of the OSB cases, being the sensitivity 100% (95% CI, 81 to 100%) and 88% (95% CI, 65 to 96%). Conclusion: Assessment of BS/BSOB ratio and four-line view in NT images is feasible detecting affected by OSB with high sensitivity. The presence of associated anomalies or of an enlarged NT enhances the early detection. PMID- 25123520 TI - Perinatal outcomes from the use of antiepileptic drugs during pregnancy: a case control study. AB - OBJECTIVE: To evaluate the perinatal results from epileptic women using antiepileptic drugs during prenatal care. METHODS: This was a retrospective longitudinal study assessing the perinatal results of women exposed to antiepileptic drugs during pregnancy, and we compared these results with those of pregnant women who were not exposed. The development of pregnancy, gestational age at delivery, Apgar scores, biometric data, morbidity, stillbirths and neonatal mortality were analyzed. The chi-square test and Fisher's exact test were used for the categorical variables, while Student's t-test was used for independent numerical variables. RESULTS: Over a 10-year period, 12 790 singleton gestations were analyzed, among which 104 (0.8%) consisted of epileptic pregnant women. From this total, 82 evolved to childbirth and their neonatal data were compared with those of 316 newborns from non-epileptic women. The most-used antiepileptic drug was phenobarbital in 70% of the cases. There was greater neonatal mortality (p = 0.006), occurrence of neonatal hemorrhagic disorders (p = 0.005), and occurrence of minor congenital anomalies (p = 0.03) among the children of women exposed to antiepileptic drugs. CONCLUSION: The antenatal exposure to antiepileptic drugs is associated mainly with occurrences of hemorrhagic complications during the neonatal period; furthermore, great prevalence of newborns presenting minor congenital anomalies and elevated risk of neonatal mortality. PMID- 25123519 TI - Antenatal brain injury in third trimester neonates with severe congenital anomalies: an autopsy study. AB - OBJECTIVE: With advances in therapy, more neonates with severe congenital anomalies are surviving, albeit some with neurologic disorders, possibly related to antenatal low brain blood flow. This autopsy series reports antenatal brain injury in neonates expiring due to severe anomalies, and provides correlation with umbilical cord blood gas and acid-base analysis. METHODS: We identified autopsies of third trimester neonates expiring shortly following delivery due to severe anomalies or malformations. Brain injury classified as "older" included periventricular leukomalacia, gliosis and karyorrhectic neurons, and "recent" included red neurons and reactive glial changes. RESULTS: We identified 22 cases (nine term, 13 preterm). 16 (73%) had brain injury, including 11 with older injury. Cord arterial blood was analyzed in 17, and six had pH <7 or base deficit >12 mmol/L. Four out of 5 (80%) neonates with neuronal necrosis compared to two out of 12 (17%) without had a pH <7 or base deficit >12 mmol/L (p = 0.03). Five out of nine (56%) neonates with white matter injury compared to one out of 8 (13%) without had pH <7 or base deficit >12 mmol/L (p = NS). CONCLUSIONS: Antenatal brain injury is frequent in neonates with severe congenital anomalies. Severely abnormal cord blood analysis results correlate significantly with neuronal necrosis and show a trend toward white matter injury; however, the absence of these abnormal results does not preclude the presence of brain injury. PMID- 25123521 TI - Inhibition of Na(+),K(+)-ATPase in the hypothalamus, pons and cerebellum of the offspring rat due to experimentally-induced maternal hypothyroidism. AB - Neurodevelopment is known to be particularly susceptible to thyroid hormone insufficiency and can result in extensive structural and functional deficits within the central nervous system (CNS), subsequently leading to the establishment of cognitive impairment and neuropsychiatric symptomatology. The current study evaluated the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism (as a suggestive multilevel experimental approach to the study of hypothyroidism-induced changes that has been developed and characterized by the authors) on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a CNS region-specific manner. The activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+) ATPase in the offspring hypothalamus, cerebellum and pons were assessed. The study demonstrated that maternal exposure to PTU (0.05% w/v in the drinking water) during the critical periods of neurodevelopment can result in an inhibition of hypothalamic, pontine and cerebellar Na(+),K(+)-ATPase; a major marker of neuronal excitability and metabolic energy production as well as an important regulator of important systems of neurotransmission. On the other hand, no significant changes in the activities of the herein offspring CNS regions' AChE and Mg(2+)-ATPase were recorded. The observed Na(+),K(+)-ATPase inhibition: (i) is region-specific (and non-detectable in whole brain homogenetes), (ii) could constitute a central event in the pathophysiology of clinically-relevant hypothyroidism-associated developmental neurotoxicity, (iii) occurs under all examined experimental schemes, and (iv) certainly deserves further clarification at a molecular and histopathological level. As these findings are analyzed and compared to the available literature, they also underline the need for the adoption and further study of Na(+),K(+)-ATPase activity as a consistent neurochemical marker within the context of a systematic comparative study of existing (and novel) simulation approaches to congenital and early age hypothyroidism. PMID- 25123522 TI - Use of magnetic resonance imaging in detecting subclinical synovitis in rheumatoid arthritis and correlation of imaging findings with interleukin-18 levels. AB - AIM: We studied the usefulness of magnetic resonance imaging (MRI) in detecting subclinical inflammation in patients with asymptomatic RA and tested the hypothesis of interleukin (IL)-18 as a marker of disease activity. METHODS: Thirteen RA patients with Disease Activity Score of 28 joints (DAS28) < 2.6 were evaluated. The patients underwent clinical evaluation, laboratory tests and MRI assessment. Imaging of bilateral hands and wrists was performed using validated acquisition and scoring techniques. Serum IL-18 levels were concurrently measured. RESULTS: MRI assessments showed that 92.3% and 76.9% of patients had synovitis and bone marrow edema, respectively, despite being in clinical remission. Eight out of 12 patients (66.7%) had erosions on MRI which were not visualised on plain radiographs. Of all the 182 joints studied for synovitis on MRI, only one had clinical evidence of joint swelling. Comparison of the total sum scores of synovitis between the right and left hand and wrist joints of individual patients showed a significant difference between the two sides. Measurements of IL-18 indicated that a large proportion (54%) of the patients had undetectable or very low levels of the cytokine. CONCLUSION: MRI is more sensitive in detecting erosions compared with X-rays, and is superior in its ability to detect subclinical inflammation in RA patients. Despite being in clinical remission, a large majority of patients had imaging-detected synovitis and bone marrow edema. Our study highlights the usefulness of MRI for the accurate evaluation of disease activity. In the utility of MRI, it may be important to assess bilateral hands and wrists, instead of limiting to the dominant side. PMID- 25123523 TI - Degradation and mineralization of organic UV absorber compound 2 phenylbenzimidazole-5-sulfonic acid (PBSA) using UV-254nm/H2O2. AB - Various studies have revealed the non-biodegradable and endocrine disrupting properties of sulfonated organic UV absorbers, directing people's attention toward their risks on ecological and human health and hence their removal from water. In this study, UV-254nm/H2O2 advanced oxidation process (AOP) was investigated for degrading a model UV absorber compound 2-phenylbenzimidazole-5 sulfonic acid (PBSA) and a structurally similar compound 1H-benzimidazole-2 sulfonic acid (BSA), with a specific focus on their mineralization. At 4.0mM [H2O2]0, a complete removal of 40.0MUM parent PBSA and 25% decrease in TOC were achieved with 190min of UV irradiation; SO4(2-) was formed and reached its maximum level while the release of nitrogen as NH4(+) was much lower (around 50%) at 190min. Sulfate removal was strongly enhanced by increasing [H2O2]0 in the range of 0-4.0mM, with slight inhibition in 4.0-12.0mM. Faster and earlier ammonia formation was observed at higher [H2O2]0. The presence of Br(-) slowed down the degradation and mineralization of both compounds while a negligible effect on the degradation was observed in the presence of Cl(-). Our study provides important technical and fundamental results on the HO based degradation and mineralization of SO3H and N-containing UV absorber compounds. PMID- 25123524 TI - Differentiation of histoplasma and cryptococcus in cytology smears: a diagnostic dilemma in severely necrotic cases. AB - OBJECTIVE: The correct identification of fungal organisms is important for the appropriate clinical management of patients. It becomes difficult in necrotic smears when the tissue response is not clearly discernible. It is difficult to distinguish between histoplasma and cryptococcus in severely necrotic cases, where both appear as variably sized clear refractile haloes. METHODS: Four cases of adrenal necrotic histoplasma infection were studied and the morphology was compared with that of non-necrotic histoplasmosis and cases of cryptococcal infection. Eleven cases were analysed in fine needle aspiration cytology (FNAC) smears. Ziehl-Neelsen (ZN) stain was performed to exclude tuberculosis in necrotic smears. A clinical and serology correlation was performed where available. RESULTS: Necrotic cases of histoplasma infection revealed negative refractile clear haloes similar to those of cryptococcus. Histoplasma showed methylene blue-stained organisms in ZN stains, whereas the cryptococcus cases were negative. Similar methylene blue-stained organisms were seen in non-necrotic histoplasma infection. CONCLUSION: As a result of morphological overlap between cryptococcus and histoplasma, the distinction between the two fungi can be difficult in many cases. ZN staining appears to have a role in the differentiation of these fungi in severely necrotic cases. This observation needs to be validated on a larger number of cases with complete correlation with clinical, serology and treatment records. PMID- 25123525 TI - Child marriage and its associations with controlling behaviors and spousal violence against adolescent and young women in Pakistan. AB - PURPOSE: Child marriage (before 18 years) is widely prevalent in Pakistan, and disproportionately affects young girls in rural, low-income, and poorly educated households. Our study aims to determine the associations between child marriage and controlling behaviors (CB) and spousal violence by husbands against adolescent and young women in Pakistan beyond those attributed to social vulnerabilities. METHODS: We analyzed data from the Pakistan Demographic and Health Survey, 2012-2013, of currently married women aged 15-24 years who had participated in the domestic violence module (n = 589, 22.5% [589/2,615] of the subsample aged 15-24 years) to identify differences in CB and spousal violence experiences between early (<18 years) and adult (>=18 years) ages at marriage. Associations between child marriage and CB and spousal violence by husband were assessed by calculating adjusted odds ratios (AOR) using logistic regression models after controlling for demographics, social equity indicators (education, wealth index, and rural residence), spousal age gap, and husband's education. RESULTS: Overall, 47.8% of currently married women aged 15-24 years in Pakistan were married before the age of 18 years. About one third of women aged 15-24 years in Pakistan reported experiencing CB (31.8%) and spousal violence (31.1%) by their husbands. Compared with adult marriage, child marriage was significantly associated with CB (AOR = 1.50; 95% confidence interval [CI], 1.042-2.157), any form of spousal violence (physical or emotional) (AOR = 2.03; 95% CI, 1.392 2.969), emotional violence (AOR = 1.86; 95% CI, 1.254-2.767), and physical violence (AOR = 2.44; 95% CI, 1.582-3.760), including severe physical violence (AOR = 2.57; 95% CI, 1.122-5.872). CONCLUSIONS: Effective interventions are needed to prevent child marriages and raise awareness about their negative consequences, with special reference to spousal violence. PMID- 25123515 TI - Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix: prevalence and clinical significance. AB - Abstract Objective: To determine the frequency and clinical significance of sterile and microbial-associated intra-amniotic inflammation in asymptomatic patients with a sonographic short cervix. Methods: Amniotic fluid (AF) samples obtained by transabdominal amniocentesis from 231 asymptomatic women with a sonographic short cervix [cervical length (CL) <=25 mm] were analyzed using cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra amniotic inflammation [defined as an AF interleukin (IL)-6 concentration >=2.6 ng/mL], acute histologic placental inflammation, spontaneous preterm delivery (sPTD), and the amniocentesis-to-delivery interval were examined according to the results of AF cultures, PCR/ESI-MS and AF IL-6 concentrations. Results: Ten percent (24/231) of patients with a sonographic short cervix had sterile intra amniotic inflammation (an elevated AF IL-6 concentration without evidence of microorganisms using cultivation and molecular methods). Sterile intra-amniotic inflammation was significantly more frequent than microbial-associated intra amniotic inflammation [10.4% (24/231) versus 2.2% (5/231); p < 0.001]. Patients with sterile intra-amniotic inflammation had a significantly higher rate of sPTD <34 weeks of gestation [70.8% (17/24) versus 31.6% (55/174); p < 0.001] and a significantly shorter amniocentesis-to-delivery interval than patients without intra-amniotic inflammation [median 35, (IQR: 10-70) versus median 71, (IQR: 47 98) days, (p < 0.0001)]. Conclusion: Sterile intra-amniotic inflammation is more common than microbial-associated intra-amniotic inflammation in asymptomatic women with a sonographic short cervix, and is associated with increased risk of sPTD (<34 weeks). Further investigation is required to determine the causes of sterile intra-amniotic inflammation and the mechanisms whereby this condition is associated with a short cervix and sPTD. PMID- 25123526 TI - Volume assured versus pressure preset non-invasive ventilation for compensated ventilatory failure in COPD. AB - BACKGROUND: The addition of domiciliary non-invasive ventilation (NIV) to standard therapy in chronic obstructive pulmonary disease (COPD) patients with compensated ventilatory failure (CVF) is reported to have beneficial effects. Compliance with NIV is an important factor. Volume assured NIV (va-NIV) may improve compliance and ventilation during sleep by automatically titrating ventilatory pressures. METHODS: A prospective single centre, randomised, parallel group trial comparing va-NIV and pressure preset NIV (pp-NIV) in COPD patients with CVF naive to domiciliary NIV was performed (ISCRTN91892415). The primary outcomes were arterial blood gases, mean overnight oximetry (mSpO2) and compliance after three months. Secondary outcomes included pulmonary function, exercise capacity and health-related quality of life assessment. RESULTS: Forty patients were randomised in a 1:1 ratio. The va-NIV median target minute ventilation was 8.4 L/min and pp-NIV median inspiratory pressure was 28 cmH2O. There were no significant differences between groups in primary or secondary outcomes after three months. Mean (SD) PaO2 8.7 (1.7) versus 7.9 (1.7) kPa (p = 0.19), PaCO2 6.7 (0.5) versus 7.3 (1.1) kPa (p = 0.1), mSpO2 89.7 (4.2) versus 89.8 (3.9) % (p = 0.95), compliance 5.0 (3.1) versus 4.7 (3.2) hours (p = 0.8) in va-NIV versus pp-NIV respectively. Patients allocated va-NIV spent fewer days in hospital initiating therapy 3.3 (1.6) versus 5.2 (2.8) (p = 0.02). Both groups showed significant improvements in PaCO2 and mSpO2 after three months treatment. CONCLUSIONS: Domiciliary va-NIV and pp-NIV have similar effects on physiological outcomes in COPD patients with CVF and both are well tolerated. PMID- 25123527 TI - Stable rates of neonatal sepsis in a tertiary neonatal unit. AB - AIMS: To describe the rate of early- and late-onset sepsis in neonates admitted to the neonatal intensive care unit at the Royal Women's Hospital and to compare the rate of late-onset sepsis (LOS) with a published (2008) cohort from the same unit. The secondary aim was to examine clinicians' compliance with antibiotic guidelines. METHODS: Infants born <32 weeks' gestation or <1500 g admitted between 1 July 2011 and 31 December 2011 were included. Strict definitions of sepsis and compliance with antibiotic guidelines were applied. RESULTS: One hundred and seventy-two infants met the inclusion criteria, with 152 having blood culture evaluations for early-onset sepsis (EOS) and 58 having 109 evaluations for LOS. Definite EOS occurred in 1.3% with Escherichia coli isolated. The rate of definite LOS in 2011 of 22% was not significantly different than the 27% in 2008, with coagulase-negative staphylococcus the main isolate. Antibiotic continuation beyond 72 h in infants with negative blood cultures was the main reason for non-compliance with antibiotic guidelines. CONCLUSIONS: The rate of EOS is comparable with published reports and the rate of LOS has remained stable over a 3-year period. Discontinuation of antibiotics with negative septic markers and blood cultures at 48-72 h is encouraged. PMID- 25123528 TI - Synthesis and biological evaluation of new BSH-conjugated chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer. AB - New disodium mercaptoundecahydro-closo-dodecaborate (BSH)-conjugated chlorin derivatives 11, 12, 16 and 20 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized. The in vivo biodistribution and clearance of 11, 12, 16 and 20 were investigated in tumor bearing mice. Compounds 12 and 16 showed good tumor-selective accumulation among the four derivatives. The time to maximum accumulation of compound 16 in tumor tissue was one-fourth of that of compound 12, and clearance from normal tissues of compound 16 was similar to that of compound 12. The in vivo therapeutic efficacy of PDT using 16, which has twice as many boron atoms as 12, was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light emitting diode irradiation at 6h after injection of 16. Tumor growth was significantly inhibited by PDT using 16. These results suggested that 16 is a good candidate for both PDT and BNCT of cancer. PMID- 25123529 TI - Neuroblastoma in a Patient With Spinal Muscular Atrophy Type I: Is It Just a Coincidence? AB - Spinal muscular atrophy is an autosomal recessive disorder characterized by progressive degeneration of anterior horn cells of the spinal cord resulting in hypotonia, skeletal muscle atrophy, and weakness. Herein, we report a 4-month-old male infant who presented to our hospital with an abdominal mass that was diagnosed as neuroblastoma and spinal muscular atrophy type I. We would like to discuss the course and differential diagnosis with an algorithm leading to the diagnosis in this peculiar patient. To our knowledge, coexistence of spinal muscular atrophy type I and neuroblastoma is defined for the first time in the literature. PMID- 25123530 TI - Large Artery Stroke in a Child With Hypoparathyroidism. AB - The association of hypoparathyroidism and ischemic stroke is rare in childhood. We report an interesting case of an 11-year-old girl diagnosed to have hypoparathyroidism and presented with an acute-onset right hemiparesis. Investigations revealed large artery ischemic stroke and uncontrolled hypoparathyroidism. Pediatricians and pediatric neurologists should be aware of this association in view of its potential preventive nature. PMID- 25123531 TI - The Epidemiology of Traumatic Brain Injury in Children and Youths: A Review of Research Since 1990. AB - This report reviews recent research on the epidemiology of traumatic brain injuries among children and youth aged 0 to 20 years. Studies representing populations in North America, Europe, Australia, and New Zealand yield these median estimates of the annual incidence of childhood brain injuries: 691 per 100 000 population treated in emergency departments, 74 per 100 000 treated in hospital, and 9 per 100 000 resulting in death. Males have a higher risk of injury than females: 1.4 times higher among those aged less than 10 years and 2.2 times among those older than 10 years. The leading cause of injury among children aged less than 5 years is falls, whereas the leading cause of injury among youths aged 15 years and older is motor vehicle crashes. The prevalence of disability among all persons who have sustained traumatic brain injury in childhood is unknown, but among those who were hospitalized could approximate 20%. PMID- 25123532 TI - Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) plays a role in cell cycle progression and cytoskeletal dynamics. AB - MARK4 is a serine-threonine kinase that phosphorylates MAP proteins, increasing microtubule dynamics. MARK4 differs from the other members of the MARK family for encoding two isoforms (MARK4L and MARK4S), differentially expressed in the nervous system, and for the peculiar localisation at the centrosome and the midbody. By cytofluorimetric analysis we showed that MARK4 is expressed throughout the cell cycle and preferentially activated during mitosis. Depletion of MARK4S affected the morphology and proliferation of fibroblasts and glioma cells, as the percentages of cells in S and G2/M phases were reduced and the percentage of cells in G1 was increased. In MARK4S silenced cells, centrosomes were duplicated and positioned apically to the nucleus, indicating that the centrosome cycle was altered and the cells arrested in G1 phase. Overexpression of MARK4L or MARK4S reduced the density of the microtubule network, confirming microtubules as the main target of MARK4, and revealed a novel co-localisation of MARK4 and vimentin. Taken together, our data confirm that MARK4 is a key component in the regulation of microtubule dynamics and highlight its major role in cell cycle progression, particularly at the G1/S transition. The co localisation of vimentin and MARK4L suggests that MARK4 has a wide-ranging influence on cytoskeleton. PMID- 25123534 TI - Post mortem concentrations of endogenous gamma hydroxybutyric acid (GHB) and in vitro formation in stored blood and urine samples. AB - Gamma-hydroxybutyrate (GHB) is a central nervous system depressant, primarily used as a recreational drug of abuse with numerous names. It has also been involved in various instances of drug-facilitated sexual assault due to its potential incapacitating effects. The first aim of this paper is to measure the post-mortem concentration of endogenous GHB in whole blood and urine samples of 30 GHB free-users, who have been divided according to the post-mortem interval (PMI) in three groups (first group: 24-36h; second group: 37-72h; third group: 73 192h), trying to evaluate the role of PMI in affecting post mortem levels. Second, the Authors have evaluated the new formation of GHB in vitro in blood and urine samples of the three groups, which have been stored at -20 degrees C, 4 degrees C and 20 degrees C over a period of one month. The concentrations were measured by GC-MS after liquid-liquid extraction according to the method validated and published by Elliot (For. Sci. Int., 2003). For urine samples, GHB concentrations were creatinine-normalized. In the first group the GHB mean concentration measured after autopsy was: 2.14mg/L (range 0.54-3.21mg/L) in blood and 3.90mg/g (range 0.60-4.81mg/g) in urine; in the second group it was: 5.13mg/L (range 1.11-9.60mg/L) in blood and 3.93mg/g (range 0.91-7.25mg/g) in urine; in the third group it was: 11.8mg/L (range 3.95-24.12mg/L) in blood and 9.83mg/g (range 3.67-21.90mg/g) in urine. The results obtained in blood and urine samples showed a statistically significant difference among groups (p<0.001) in the first analysis performed immediately after autopsy. Throughout the period of investigation up to 4 weeks, the comparison of storage temperatures within each group showed in blood and urine samples a mean difference at 20 degrees C compared to -20 degrees C not statistically significant at the 10% level. These findings allow us to affirm that the PMI strongly affects the post mortem production of GHB in blood and urine samples. Regarding the new formation of GHB in vitro both in blood and urine samples of the three groups, which have been stored at -20 degrees C, 4 degrees C and 20 degrees C over a period of one month, although there was no significant increases of GHB levels throughout the period of investigation, the lowest increases were found both in blood and urine at -20 degrees C, therefore we recommend the latter as optimal storage temperature. PMID- 25123533 TI - A quantitative multiplexed mass spectrometry assay for studying the kinetic of residue-specific histone acetylation. AB - Histone acetylation is involved in gene regulation and, most importantly, aberrant regulation of histone acetylation is correlated with major human diseases. Although many lysine acetyltransferases (KATs) have been characterized as being capable of acetylating multiple lysine residues on histones, how different factors such as enzyme complexes or external stimuli (e.g. KAT activators or inhibitors) alter KAT specificity remains elusive. In order to comprehensively understand how the homeostasis of histone acetylation is maintained, a method that can quantitate acetylation levels of individual lysines on histones is needed. Here we demonstrate that our mass spectrometry (MS)-based method accomplishes this goal. In addition, the high throughput, high sensitivity, and high dynamic range of this method allows for effectively and accurately studying steady-state kinetics. Based on the kinetic parameters from in vitro enzymatic assays, we can determine the specificity and selectivity of a KAT and use this information to understand what factors influence histone acetylation. These approaches can be used to study the enzymatic mechanisms of histone acetylation as well as be adapted to other histone modifications. Understanding the post-translational modification of individual residues within the histones will provide a better picture of chromatin regulation in the cell. PMID- 25123535 TI - Arsenic trioxide prevents rat pulmonary fibrosis via miR-98 overexpression. AB - AIMS: This study aimed to investigate the pathogenesis mechanisms of bleomycin (BLM)-induced pulmonary fibrosis (PF) in Sprague-Dawley rats and explore the anti fibrotic role of arsenic trioxide (As2O3) in preventing PF. MAIN METHODS: Intratracheal instillation of BLM was performed to establish PF rat models. The treatment group was treated with As2O3 (0.4 mg/kg/day). Morphological changes were observed by hematoxylin-eosin and Masson staining. Related proteins were determined by immunohistochemistry, immunofluorescence, and Western blot. MicroRNA detection was performed by quantitative real-time polymerase chain reaction. KEY FINDINGS: As a novel miRNA in PF, miR-98 decreased in the fibrotic lung tissues. Based on microRNA analysis software, we found that Stat3-3'-UTR is targeted by miR-98. Then, we found that Stat3 was activated with PF development and the expression of Stat3 and p-Stat3 was significantly increased in BLM induced PF at day 28 compared with saline-treated rats. Our results showed that both Stat3 and p-Stat3 were significantly decreased in miR-98-treated A549 cells compared with that in mu-98-treated cultures or untreated controls. The fibrotic marker alpha-SMA was upregulated, whereas E-cadherin was inhibited in fibrotic lung tissues. The ratio of apoptotic factors Bax/Bcl-2 increased with the development of fibrosis. Furthermore, As2O3 treatment prevented lung interstitial thickening and inhibited the collagen type I and hydroxyproline, thereby preventing the development of PF. As2O3 also significantly down-regulated alpha SMA but increased E-cadherin and miR-98 levels. SIGNIFICANCE: The study revealed that arsenic trioxide prevented rat PF by up-regulation of miR-98 and inhibition of its downstream Stat3 signals. PMID- 25123536 TI - Insulin acutely triggers transcription of Slc2a4 gene: participation of the AT rich, E-box and NFKB-binding sites. AB - AIMS: The insulin-sensitive glucose transporter protein GLUT4 (solute carrier family 2 member 4 (Slc2a4) gene) plays a key role in glycemic homeostasis. Decreased GLUT4 expression is a current feature in insulin resistant conditions such as diabetes, and the restoration of GLUT4 content improves glycemic control. This study investigated the effect of insulin upon Slc2a4/GLUT4 expression, focusing on the AT-rich element, E-box and nuclear factor NF-kappa-B (NFKB) site. MAIN METHODS: Rat soleus muscles were incubated during 180 min with insulin, added or not with wortmannin (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PI3K)-inhibitor), ML9 (serine/threonine protein kinase (AKT) inhibitor) and tumor necrosis factor (TNF, GLUT4 repressor), and processed for analysis of GLUT4 protein (Western blotting); Slc2a4, myocyte enhancer factor 2a/d (Mef2a/d), hypoxia inducible factor 1a (Hif1a), myogenic differentiation 1 (Myod1) and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (Nfkb1) messenger ribonucleic acids (mRNAs) (polymerase chain reaction (PCR)); and AT-rich- (myocyte-specific enhancer factor 2 (MEF2) binding site), E-box- (hypoxia inducible factor 1 alpha (HIF1A)- and myoblast determination protein 1 (MYOD1)-binding site), and NFKB-binding activity (electrophoretic mobility assay). KEY FINDINGS: Insulin increased Slc2a4 mRNA expression (140%) and nuclear proteins binding to AT-rich and E-box elements (~90%), all effects were prevented by wortmannin and ML9. Insulin also increased Mef2a/d and Myod1 mRNA expression, suggesting the participation of these transcriptional factors in the Slc2a4 enhancing effect. Conversely, insulin decreased Nfkb1 mRNA expression and protein binding to the NFKB-site (~50%). Furthermore, TNF-induced inhibition of GLUT4 expression (~40%) was prevented by insulin in an NFKB-binding repressing mechanism. GLUT4 protein paralleled the Slc2a4 mRNA regulations. SIGNIFICANCE: Insulin enhances the Slc2a4/GLUT4 expression in the skeletal muscle by activating AT-rich and E-box elements, in a PI3K/AKT-dependent mechanism, and repressing NFKB-site activity as well. These results unravel how post-prandial increase of insulin may guarantee GLUT4 expression, and how the insulin signaling impairment can participate in insulin resistance-induced repression of GLUT4. PMID- 25123538 TI - Efficient heteronuclear decoupling in MAS solid-state NMR using non-rotor synchronized rCW irradiation. AB - We present new non-rotor-synchronized variants of the recently introduced refocused continuous wave (rCW) heteronuclear decoupling method significantly improving the performance relative to the original rotor-synchronized variants. Under non-rotor-synchronized conditions the rCW decoupling sequences provide more efficient decoupling, are easier to setup, and prove more robust towards experimental parameters such as radio frequency (rf) field amplitude and spinning frequency. This is demonstrated through numerical simulations substantiated with experimental results under different sample spinning and rf field amplitude conditions for powder samples of U-(13)C-glycine and U-(13)C-L-histidine.HCl.H2O. PMID- 25123537 TI - Leptin-mediated inflammatory signaling crucially links visceral fat inflammation to obesity-associated beta-cell dysfunction. AB - AIM: This study aimed to examine the causal relationship between adipokines released from visceral fat and pancreatic beta-cell dysfunction in the state of obesity inflammation. MAIN METHODS: Adipose tissue and adipocyte conditioned medium were obtained from epididymal fat of B6 mice on regular or high fat diet for 16 weeks. The latter were classified into two groups: overweight (OW, 40+/ 2g) and obese (OB, 50+/-2g). Isolated mouse islets and NIT-1 cells were used to evaluate beta-cell function. KEY FINDINGS: Fasting glucose, leptin, and interleukin-6 levels were increased in OW mice and were further elevated in OB mice. Adipocyte size and number of adipose macrophage infiltrations showed a similar trend. The augmentation of homeostasis model assessment of insulin resistance, islet hyperplasia and macrophage infiltration was noted only in OB mice. The stimulation index was lower, but reactive oxygen species production was higher in islets isolated from OB mice than from controls. In epididymal fat conditioned medium, the increases in leptin, IL-6 and TNF-alpha production in OW mice were further elevated in OB mice except TNF-alpha. Adipose tissue conditioned medium suppressed the stimulation index of islets isolated from B6 mice but not from db/db mice. The suppressive effect was also reversed by co treatment with N-acetylcysteine or NS-398 (a selective cyclooxygenase-2 inhibitor). SIGNIFICANCE: A markedly elevated leptin production from inflamed visceral fat could deteriorate beta-cell function via leptin receptor-mediated oxidative stress and cyclooxygenase-2 activation in the development of obesity. PMID- 25123539 TI - Determining pore length scales and pore surface relaxivity of rock cores by internal magnetic fields modulation at 2MHz NMR. AB - Pore length scales and pore surface relaxivities of rock cores with different lithologies were studied on a 2MHz Rock Core Analyzer. To determine the pore length scales of the rock cores, the high eigenmodes of spin bearing molecules satisfying the diffusion equation were detected with optimized encoding periods in the presence of internal magnetic fields Bin. The results were confirmed using a 64MHz NMR system, which supports the feasibility of high eigenmode detection at fields as low as 2MHz. Furthermore, this methodology was combined with relaxometry measurements to a two-dimensional experiment, which provides correlation between pore length and relaxation time. This techniques also yields information on the surface relaxivity of the rock cores. The estimated surface relaxivities were then compared to the results using an independent NMR method. PMID- 25123540 TI - Achieving 1% NMR polarization in water in less than 1min using SABRE. AB - The development of biocompatible hyperpolarized media is a crucial step towards application of hyperpolarization in vivo. This article describes the achievement of 1% hyperpolarization of 3-amino-1,2,4-triazine protons in water using the parahydrogen induced polarization technique based on signal amplification by reversible exchange (SABRE). Polarization was achieved in less than 1 min. PMID- 25123541 TI - A 3D experiment that provides isotropic homonuclear correlations of half-integer quadrupolar nuclei. AB - Two 3D experiments, capable of producing enhanced resolution two-spin double quantum (DQ) homonuclear correlations for half-integer quadrupolar nuclei, are described. The first uses a split-t1 MQMAS sequence followed by a sandwiched oR(3) symmetry-based dipolar recoupling sequence to directly excite DQ coherences. In this case an isotropic single-quantum (SQ) coherence starts the homonuclear DQ excitation. In the second experiment a single strong pulse is used to create triple quantum (TQ) coherence followed by a further single pulse conversion to zero-order before a non-sandwiched oR(3) DQ sequence. The first experiment is demonstrated using (87)Rb in RbNO3, with three Rb sites in a ~5ppm range, and the second to (11)B in caesium triborate, CsB3O5, with two three coordinated sites separated by ~2ppm and one four-coordinated boron site. In both cases, all sites are clearly resolved and their connections observed. The second experiment has higher sensitivity and a good signal to noise is obtained in a reasonable time despite the long T1 relaxation time of (11)B in this material. PMID- 25123542 TI - The interaction of a cobalt porphyrin with cancer-associated nitrosamines. AB - A cobalt porphyrin (CY-B) was presented, and its interaction with tobacco specific nitrosamines (TSNAs) was investigated by UV-Vis spectroscopy and high resolution mass spectrometry. The results revealed that the stoichiometry of the host-guest interaction was 1:2 and that the binding constant between CY-B and TSNAs was within the range of 0.78*10(8)-7.83*10(8)M(-2). The coordination strength between CY-B and TSNAs decreased in the sequence of NNN>NAB>NAT>NNK based on the binding constant. The interaction mechanism of CY-B with TSNAs involved a coordination interaction, and the pi-pi interaction between the porphyrin macrocycle and the aromatic frame of the TSNAs pyridines may also have been a driving force. The measured thermodynamic properties demonstrated that the reaction of CY-B with TSNAs was spontaneous and that the driving force for the interaction was a change in enthalpy. The reaction was exothermic, and an increasing temperature inhibited the interaction. The IR spectrum of the complex revealed that the NNO group of TSNAs and the metal cobalt of CY-B formed the six coordinate complex. PMID- 25123544 TI - Identifying the contents of a type 1 diabetes outpatient care program based on the self-adjustment of insulin using the Delphi method. AB - AIM: The objective of this study is to identify the items necessary for an outpatient care program based on the self-adjustment of insulin for type 1 diabetes patients. METHODS: Two surveys based on the Delphi method were conducted. The survey participants were 41 certified diabetes nurses in Japan. An outpatient care program based on the self-adjustment of insulin was developed based on pertinent published work and expert opinions. RESULTS: There were a total of 87 survey items in the questionnaire, which was developed based on the care program mentioned earlier, covering matters such as the establishment of prerequisites and a cooperative relationship, the basics of blood glucose pattern management, learning and practice sessions for the self-adjustment of insulin, the implementation of the self-adjustment of insulin, and feedback. The participants' approval on items in the questionnaires was defined at 70%. Participants agreed on all of the items in the first survey. Four new parameters were added to make a total of 91 items for the second survey and participants agreed on the inclusion of 84 of them. CONCLUSION: Items necessary for a type 1 diabetes outpatient care program based on self-adjustment of insulin were subsequently selected. It is believed that this care program received a fairly strong approval from certified diabetes nurses; however, it will be necessary to have the program further evaluated in conjunction with intervention studies in the future. PMID- 25123543 TI - Adverse event reporting in nonpharmacologic, noninterventional pain clinical trials: ACTTION systematic review. AB - Assessment of treatment safety is 1 of the primary goals of clinical trials. Organizations and working groups have created reporting guidelines for adverse events (AEs). Previous research examining AE reporting for pharmacologic clinical trials of analgesics in major pain journals found many reporting inadequacies, suggesting that analgesic trials are not adhering to existing AE reporting guidelines. The present systematic review documented AE reporting in 3 main pain journals for nonpharmacologic, noninterventional (NP/NI) trials examining pain treatments. To broaden our pool of nonpharmacologic trials, we also included trials examining acupuncture, leech therapy, and noninvasive stimulation techniques (eg, transcutaneous electrical nerve stimulation). We documented AE reporting at 2 levels of specificity using coding manuals based on the Consolidated Standards of Reporting Trials (CONSORT) harms reporting standards and Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) AE reporting checklist. We identified a number of inadequacies in AE reporting across the 3 journals. For example, using the ACTTION coding manual, we found that less than one-half of the trials reported specific AE assessment methods; approximately one-third of the trials reported withdrawals due to AEs for each study arm; and about one-fourth of the trials reported all specific AEs. We also examined differences in AE reporting across several trial characteristics, finding that AE reporting was generally more detailed in trials with patients versus those using healthy volunteers undergoing experimentally evoked pain. These results suggest that investigators conducting and reporting NP/NI clinical trials are not adequately describing the assessment and occurrence of AEs. PMID- 25123545 TI - A pleomorphic carcinoma of the lung producing multiple cytokines and forming a rapidly progressive mass-like opacity. AB - BACKGROUND: Lung cancer cells have been reported to produce cytokines, resulting in systemic reactions. There have been few reports showing that these cytokines induced the formation of an inflammatory mass around lung cancers. CASE PRESENTATION: We encountered a patient with a pleomorphic carcinoma of the lung. This tumor produced interleukin (IL)-8, granulocyte colony-stimulating factor and IL-6, which in turn recruited inflammatory cells, such as CD8 positive lymphocytes, around the tumor, resulting in a rapidly growing tumor shadow. CONCLUSION: 18 F-fluoro-deoxy-glucose positron emission tomography, in addition to a conventional radiological approach such as computed tomography, may detect immunological responses around a tumor. PMID- 25123546 TI - Demographic history and gene flow during silkworm domestication. AB - BACKGROUND: Gene flow plays an important role in domestication history of domesticated species. However, little is known about the demographic history of domesticated silkworm involving gene flow with its wild relative. RESULTS: In this study, four model-based evolutionary scenarios to describe the demographic history of B. mori were hypothesized. Using Approximate Bayesian Computation method and DNA sequence data from 29 nuclear loci, we found that the gene flow at bottleneck model is the most likely scenario for silkworm domestication. The starting time of silkworm domestication was estimated to be approximate 7,500 years ago; the time of domestication termination was 3,984 years ago. Using coalescent simulation analysis, we also found that bi-directional gene flow occurred during silkworm domestication. CONCLUSIONS: Estimates of silkworm domestication time are nearly consistent with the archeological evidence and our previous results. Importantly, we found that the bi-directional gene flow might occur during silkworm domestication. Our findings add a dimension to highlight the important role of gene flow in domestication of crops and animals. PMID- 25123547 TI - Camello, a novel family of Histone Acetyltransferases that acetylate histone H4 and is essential for zebrafish development. AB - In this study, we have investigated genome-wide occurrence of Histone Acetyltransferases (HATs) in genomes of Mus musculus and Danio rerio on the basis of presence of HAT domain. Our study identified a group of proteins that lacks characteristic features of known HAT families, relatively smaller in size and has no other associated domains. Most of the proteins in this unclassified group are Camello proteins, which are not yet known and classified as functional HATs. Our in vitro and in vivo analysis revealed that Camello family proteins are active HATs and exhibit specificity towards histone H4. Interestingly, Camello proteins are among the first identified HATs showing perinuclear localization. Moreover, Camello proteins are evolutionarily conserved in all chordates and are observed for the first time in cnidarians in phylogeny. Furthermore, knockdown of Camello protein (CMLO3) in zebrafish embryos exhibited defects in axis elongation and head formation. Thus, our study identified a novel family of active HATs that is specific for histone H4 acetylation, exhibits perinuclear localization and is essential for zebrafish development. PMID- 25123548 TI - Relating working memory to compression parameters in clinically fit hearing AIDS. AB - PURPOSE: Several laboratory studies have demonstrated that working memory may influence response to compression speed in controlled (i.e., laboratory) comparisons of compression. In this study, the authors explored whether the same relationship would occur under less controlled conditions, as might occur in a typical audiology clinic. METHOD: Participants included 27 older adults who sought hearing care in a private practice audiology clinic. Working memory was measured for each participant using a reading span test. The authors examined the relationship between working memory and aided speech recognition in noise, using clinically fit hearing aids with a range of compression speeds. RESULTS: Working memory, amount of hearing loss, and age each contributed to speech recognition, but the contribution depended on the speed of the compression processor. For fast acting compression, the best performance was obtained by patients with high working memory. For slow-acting compression, speech recognition was affected by age and amount of hearing loss but was not affected by working memory. CONCLUSIONS: Despite the expectation of greater variability from differences in compression implementation, number of compression channels, or attendant signal processing, the relationship between working memory and compression speed showed a similar pattern as results from more controlled, laboratory-based studies. PMID- 25123550 TI - GRAIDs: a framework for closing the gap in the availability of health promotion programs and interventions for people with disabilities. AB - BACKGROUND: Evidence-based health promotion programs developed and tested in the general population typically exclude people with disabilities. To address this gap, a set of methods and criteria were created to adapt evidence-based health promotion programs for people with disabilities. In this first study, we describe a framework for adapting evidence-based obesity prevention strategies for people with disabilities. We illustrate how the framework has been used to adapt the U.S. Centers for Disease Control and Prevention's (CDC) obesity prevention strategies for individuals with physical and developmental disabilities. METHODS: The development of inclusion guidelines, recommendations and adaptations for obesity prevention (referred to as GRAIDs--Guidelines, Recommendations, Adaptations Including Disability) consists of five components: (i) a scoping review of the published and grey literature; (ii) an expert workgroup composed of nationally recognized leaders in disability and health promotion who review, discuss and modify the scoping review materials and develop the content into draft GRAIDs; (iii) focus groups with individuals with disabilities and their family members (conducted separately) who provide input on the potential applicability of the proposed GRAIDs in real world settings; (iv) a national consensus meeting with 21 expert panel members who review and vote on a final set of GRAIDs; and (v) an independent peer review of GRAIDs by national leaders from key disability organizations and professional groups through an online web portal. RESULTS: This is an ongoing project, and to date, the process has been used to develop 11 GRAIDs to coincide with 11 of the 24 CDC obesity prevention strategies. CONCLUSION: A set of methods and criteria have been developed to allow researchers, practitioners and government agencies to promote inclusive health promotion guidelines, strategies and practices for people with disabilities. Evidence-based programs developed for people without disabilities can now be adapted for people with disabilities using the GRAIDs framework. PMID- 25123549 TI - Younger age, higher body mass index and lower adiponectin concentration predict higher serum thromboxane B2 level in aspirin-treated patients with type 2 diabetes: an observational study. AB - BACKGROUND: Evidence from the literature suggests diminished acetylsalicylic acid (ASA) treatment efficacy in type 2 diabetes (DM2). High on-aspirin platelet reactivity (HAPR) in DM2 has been linked to poor glycemic and lipid control. However, there are no consistent data on the association between HAPR and insulin resistance or adipose tissue metabolic activity. The aim of this study was to assess the relationship between laboratory response to ASA and metabolic control, insulin resistance and adipokines in DM2. METHODS: A total of 186 DM2 patients treated with oral antidiabetic drugs and receiving 75 mg ASA daily were included in the analysis. Response to ASA was assessed by measuring serum thromboxane B2 (TXB2) concentration and expressed as quartiles of TXB2 level. The achievement of treatment targets in terms of glycemic and lipid control, insulin resistance parameters (including Homeostatic Model Assessment-Insulin Resistance, HOMA-IR, index), and serum concentrations of high-molecular weight (HMW) adiponectin, leptin and resistin, were evaluated in all patients. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors of serum TXB2 concentration above the upper quartile and above the median. RESULTS: Significant trends in age, body mass index (BMI), HOMA-IR, HMW adiponectin concentration, C-reactive protein concentration and the frequency of achieving target triglyceride levels were observed across increasing quartiles of TXB2. In a multivariate analysis, only younger age and higher BMI were independent predictors of TXB2 concentration above the upper quartile, while younger age and lower HMW adiponectin concentration were predictors of TXB2 concentration above the median. CONCLUSIONS: These results suggest that in DM2, the most important predictor of HAPR is younger age. Younger DM2 patients may therefore require total daily ASA doses higher than 75 mg, preferably as a twice daily regimen, to achieve full therapeutic effect. Higher BMI and lower HMW adiponectin concentration were also associated with less potent ASA effect. This is the first study to demonstrate an association of lower adiponectin concentration with higher serum TXB2 level in patients treated with ASA. PMID- 25123551 TI - Sweet taste sensitivity in pre-diabetics, diabetics and normoglycemic controls: a comparative cross sectional study. AB - BACKGROUND: Increasing prevalence of pre-diabetes is an emerging public health problem. Decrease in sweet taste sensitivity which can lead to an increase in sugar intake might be a factor driving them to overt diabetes. The aim of the present study was to assess the sweet taste sensitivity in pre-diabetics in comparison with diabetics and with normoglycemic controls. METHODS: Forty pre diabetics, 40 diabetics and 34 normoglycemic controls were studied. The three groups were matched for age, sex and BMI. The division into groups was based on their glycated hemoglobin levels. The detection and recognition thresholds were determined by the multiple forced-choice method using sucrose solutions prepared in 1/4 log dilutions. The intensities of perceived sensations for a series of suprathreshold concentrations of sucrose solutions prepared in 1/2 log dilution were determined by rating on a visual analogue scale. Statistical analyses were performed by SPSS version 21. RESULTS: The mean (SD) detection thresholds of diabetic, pre-diabetic and normoglycemic groups were 0.025 (0.01), 0.018 (0.01) and 0.015 (0.01) respectively with a significant increase in diabetic group compared to normoglycemic group (p = 0.03). The mean recognition thresholds were not different among the three groups. When the intensity ratings for suprathreshold concentrations of sucrose were compared between the three groups, for all suprathreshold concentrations tested, significant differences were observed across the four concentrations (p < 0.001) and between groups in suprathreshold ratings (p < 0.05). Further analysis showed that the diabetic group had significantly lower suprathreshold ratings than the normoglycemic group (p < 0.001). Although all mean suprathreshold intensity ratings of the pre diabetic group were between the normoglycemic and diabetic groups, the differences were not significant. CONCLUSIONS: This is the first study to demonstrate the sweet taste sensitivity in pre-diabetics. The findings of the present study do not support the hypothesis of decreased sweet taste sensitivity of pre-diabetics. However, the results confirm the previous findings of blunted taste response in diabetics. The observation of pre-diabetics having intermediate values for all taste thresholds and suprathreshold ratings warrants a future investigation with a larger pre-diabetic sample recruited with more specific screening criteria to test this hypothesis further. PMID- 25123552 TI - Population model of longitudinal FEV1 data in asthmatics: meta-analysis and predictability of placebo response. AB - Asthma is an obstructive lung disease where the mechanism of disease progression is not fully understood hence motivating the use of empirical models to describe the evolution of the patient's health state. With reference to placebo response, measured in terms of FEV1 (Forced Expiratory Volume in 1 s), a range of empirical models taken from the literature were compared at a single trial level. In particular, eleven GSK trials lasting 12 weeks in mild-to-moderate asthma were used for the modelling of longitudinal placebo responses. Then, the chosen exponential model was used to carry out an individual participant data meta analysis on eleven trials. A covariate analysis was also performed to find relevant covariates in asthma to be accounted for in the meta-analysis model. Age, gender, and height were found statistically significant (e.g. the taller the patients the higher the FEV1, the older the patients the lower the FEV1, and females have lower FEV1). By truncating each trial at week 4, the predictive properties of the meta-analysis model were also investigated, showing its ability to predict long-term FEV1 response from truncated trials. Summarizing, the study suggests that: (i) the exponential model effectively describes the placebo response; (ii) the meta-analysis approach may prove helpful to simulate new trials as well as to reduce trial duration in view of its predictive properties; (iii) the inclusion of available covariates within the meta-analysis model provides a reduction of the inter-individual variability. PMID- 25123553 TI - Goal setting and knowledge generation through health policy and systems research in low- and middle-income countries. AB - The importance of health policy and systems research (HPSR) and its role in aiding health system reforms has been increasingly recognized in recent years within the World Health Organization (WHO). An assessment of the 71 WHO Country Cooperation Strategies (CCS) that are publicly available and were published in English in 2012 was completed to determine the extent to which HPSR goals are incorporated at the global level. A review was then conducted using a Medline database search to determine the number of articles published by countries with HPSR goals. Sixty-six out of the 71 (93%) available CCS describe HPSR as an objective or strategy for achieving health system priorities. However, only 52 out of the 66 countries (79%) have any publications involving HPSR during their most recent CCS cycle. This suggests that although health systems strengthening through HPSR is increasingly emphasized by the WHO and country health ministries, actual HPSR progress may still be lacking. There is a need and an opportunity for the WHO and other global health agencies to focus on providing the necessary tools and building HPSR capacity in low- and middle-income countries. PMID- 25123554 TI - Positive and negative affective states and disease activity in ankylosing spondylitis. AB - The aim of the study was to explore the influence of psychological affective states such as cheerfulness and bad mood on self-reported disease activity in patients with ankylosing spondylitis (AS) while controlling for demographic and clinical variables. Patients attending a biological therapy unit were selected for a cross-sectional study if they met the criteria for AS and were already receiving treatment. Their psychological affective state was assessed with the state version of the State-Trait Cheerfulness Inventory. Clinical variables included were patient-reported disease activity using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and acute-phase reactants. We performed univariate and multivariate analyses to verify the robustness of the relationship between psychological affective states and disease activity. We also explored whether disease activity, measured either by self-report or by acute phase reactants, was influenced by patient's overall affective state. In the recruited 31 patients with AS, overall affective state contributed significantly to the variance in BASDAI scores, adding 21.8% to the overall R-square of the predictive power of clinical and demographic variables (combined R-square = 17%). A higher positive affective state was associated with lower values of C-reactive protein (p < 0.05). Results of a bootstrapping procedure showed that the relationship between C-reactive protein levels and BASDAI scores was mediated by overall affective state. In patients with AS, affective state can induce variability in self-reported disease activity. Patients' overall affective state can explain the relationship between acute-phase reactants and self-reported scores. These findings suggest interesting possibilities for the monitoring of disease activity in AS. PMID- 25123555 TI - Toxicity of nanomaterials; an undermined issue. AB - Nanomaterials are employed in extensive variety of commercial products such as electronic components, cosmetics, food, sports equipment, biomedical applications, and medicine. With the increasing utilization of engineered nanomaterials, the potential exposure of human to nanoparticles is rapidly increasing. Nowadays when new nanomaterials with new applications are introduced, mostly good and positive effects are mentioned whereas possible hazards arising from nanosize of the compounds are undermined. Toxicology studies of nanomaterials demonstrate some adverse effects in some human organs such as central nerve system, immune system, and lung. There is lack of complete information about human toxicity and environmental waste of nanomaterials. We aimed to highlight current toxicological concerns of potentially useful nanomaterials which are now used in pharmaceutical and biomedical sciences. PMID- 25123557 TI - Bioreactor study employing bacteria with enhanced activity toward cyanobacterial toxins microcystins. AB - An important aim of white (grey) biotechnology is bioremediation, where microbes are employed to remove unwanted chemicals. Microcystins (MCs) and other cyanobacterial toxins are not industrial or agricultural pollutants; however, their occurrence as a consequence of human activity and water reservoir eutrophication is regarded as anthropogenic. Microbial degradation of microcystins is suggested as an alternative to chemical and physical methods of their elimination. This paper describes a possible technique of the practical application of the biodegradation process. The idea relies on the utilization of bacteria with a significantly enhanced MC-degradation ability (in comparison with wild strains). The cells of an Escherichia coli laboratory strain expressing microcystinase (MlrA) responsible for the detoxification of MCs were immobilized in alginate beads. The degradation potency of the tested bioreactors was monitored by HPLC detection of linear microcystin LR (MC-LR) as the MlrA degradation product. An open system based on a column filled with alginate entrapped cells was shown to operate more efficiently than a closed system (alginate beads shaken in a glass container). The maximal degradation rate calculated per one liter of carrier was 219.9 ug h-1 of degraded MC-LR. A comparison of the efficiency of the described system with other biological and chemo-physical proposals suggests that this new idea presents several advantages and is worth investigating in future studies. PMID- 25123556 TI - Synthesis and analgesic effects of MU-TRTX-Hhn1b on models of inflammatory and neuropathic pain. AB - MU-TRTX-Hhn1b (HNTX-IV) is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic MU-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. MU-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of MU-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of MU-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that MU-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design. PMID- 25123559 TI - Protective antigen-specific memory B cells persist years after anthrax vaccination and correlate with humoral immunity. AB - Anthrax Vaccine Adsorbed (AVA) generates short-lived protective antigen (PA) specific IgG that correlates with in vitro toxin neutralization and protection from Bacillus anthracis challenge. Animal studies suggest that when PA-specific IgG has waned, survival after spore challenge correlates with an activation of PA specific memory B cells. Here, we characterize the quantity and the longevity of AVA-induced memory B cell responses in humans. Peripheral blood mononuclear cells (PBMCs) from individuals vaccinated >=3 times with AVA (n = 50) were collected early (3-6 months, n = 27) or late after their last vaccination (2-5 years, n = 23), pan-stimulated, and assayed by ELISPOT for total and PA-specific memory B cells differentiated into antibody secreting cells (ASCs). PA-specific ASC percentages ranged from 0.02% to 6.25% (median: 1.57%) and did not differ between early and late post-vaccination individuals. PA-specific ASC percentages correlated with plasma PA-specific IgG (r = 0.42, p = 0.03) and toxin neutralization (r = 0.52, p = 0.003) early post vaccination. PA-specific ASC percentages correlated with supernatant anti-PA both early (r = 0.60, p = 0.001) and late post vaccination (r = 0.71, p < 0.0001). These data suggest PA-specific memory B cell responses are long-lived and can be estimated after recent vaccination by the magnitude and neutralization capacity of the humoral response. PMID- 25123560 TI - [Visual diagnosis while performing transurethral resection of bladder tumors: power or myth?]. AB - INTRODUCTION: The gold standard for diagnosis and immediate therapy of bladder cancer is a transurethral resection (TURB) followed by histopathologic evaluation. The aim of this study was to assess the reliability of visual diagnosis by the operating urologist concerning dignity (malignant/benign) and staging compared to histopathologic evaluation. This is especially crucial since early mitomycin C instillation is based on the urologist's first impression. STUDY DESIGN AND METHODS: This prospective study included 311 cases of TURB from five German institutions. Surgeons were asked to estimate dignity of the neoplasm, tumor stage, and grade according to a standardized questionnaire. RESULTS: The subjective estimation/visual diagnosis of the operating urologist achieved a sensitivity with respect to identifying malignant tumors as such of 97%, while specificity was only 41%. Accordingly, the positive (PPV) and negative predictive values (NPV) were 76% and 88%, respectively. In general, muscle invasive cancer was predicted more often than confirmed by pathology (PPV 52%). However, whenever muscle invasive cancer was excluded by the urologist, this was confirmed by the pathologist in most the cases (NPV 95%). The educational degree did not influence the reliability and predictive value of visual diagnosis. CONCLUSION: This study shows that urologists cannot reliably distinguish benign from malignant lesions of bladder mucosa-regardless of their educational degree. A reliable diagnosis of a pathologist is definitely needed to plan final therapeutic steps. PMID- 25123558 TI - Molecular approaches to improve the insecticidal activity of Bacillus thuringiensis Cry toxins. AB - Bacillus thuringiensis (Bt) is a gram-positive spore-forming soil bacterium that is distributed worldwide. Originally recognized as a pathogen of the silkworm, several strains were found on epizootic events in insect pests. In the 1960s, Bt began to be successfully used to control insect pests in agriculture, particularly because of its specificity, which reflects directly on their lack of cytotoxicity to human health, non-target organisms and the environment. Since the introduction of transgenic plants expressing Bt genes in the mid-1980s, numerous methodologies have been used to search for and improve toxins derived from native Bt strains. These improvements directly influence the increase in productivity and the decreased use of chemical insecticides on Bt-crops. Recently, DNA shuffling and in silico evaluations are emerging as promising tools for the development and exploration of mutant Bt toxins with enhanced activity against target insect pests. In this report, we describe natural and in vitro evolution of Cry toxins, as well as their relevance in the mechanism of action for insect control. Moreover, the use of DNA shuffling to improve two Bt toxins will be discussed together with in silico analyses of the generated mutations to evaluate their potential effect on protein structure and cytotoxicity. PMID- 25123561 TI - [Influence of ureter stenting before ureterorenoscopic treatment of ureteral calculi]. AB - BACKGROUND: Due to a worldwide rise of incidence, urolithiasis presents an increasing strain on the health system. Ureterorenoscopy (URS) is a standard treatment to extract stones in case of ureteral calculi. To increase the success rate of URS and to minimize complications, preoperative ureteral stenting (prestenting) has previously been described as suitable. However, published data are still conflicting. This article describes our single-center experience on the influence of prestenting on the outcome of ureterorenoscopic stone therapy. METHODS: A total of 442 patients who had undergone ureterorenoscopic stone extraction at the Wolfsburg Clinic between 2010 and 2011 were retrospectively evaluated regarding peri- and postoperative results. The Fisher's exact, the chi(2), and the Mann-Whitney U test were used to compare the group of patients with and without prestenting. RESULTS: Even though patients with prestenting suffered from stones with larger diameter that were more frequently located in the proximal ureter, the rates for postoperative stenting, perioperative complications, and retreatment were much lower then in the group of patients without prestenting (p<0.001). Furthermore, patients who had received prestenting had a significantly shorter hospital stay (median, 3 vs. 2 days, p<0.001) and higher rates of stone clearance (83.0 vs. 69.7%, p=0.001). CONCLUSION: According to our retrospective monocentric analysis, prestenting may significantly reduce the risk of complications as well as intra-/post-URS restenting and can increase the rate of complete stone clearance. PMID- 25123562 TI - Additive effect of elcatonin to risedronate for chronic back pain and quality of life in postmenopausal women with osteoporosis: a randomized controlled trial. AB - Calcitonin has been reported to reduce acute and chronic back pain in osteoporotic patients. The additive effect of calcitonin with a bisphosphonate on chronic back pain remains unclear. The purpose of this study was to evaluate the effect of combining elcatonin (eel calcitonin) with risedronate for patients with chronic back pain. Forty-five postmenopausal women diagnosed as having osteoporosis with chronic back pain persisting for more than 3 months, after excluding women with fresh vertebral fractures within the last 6 months, were randomly allocated to a risedronate group (risedronate alone, n = 22) and a combined group (risedronate and elcatonin, n = 23). The study period was 6 months. Pain was evaluated with a visual analogue scale (VAS) and the Roland Morris questionnaire (RDQ). Back extensor strength, bone mineral density, and quality of life on the SF-36 and the Japanese osteoporosis quality of life score were also evaluated. Significant improvements were found in the combined group for VAS at final follow-up compared with baseline and 3 months, mental health status on the SF-36, and JOQOL domains for back pain and general health. The JOQOL domain for back pain improved significantly, but no change was found in the VAS or other domains in the risedronate group. Bone mineral density increased significantly in the two groups, but no significant difference was found between the groups. Back extensor strength did not change in both groups. In conclusion, the use of elcatonin in addition to risedronate for more than 3 months reduced chronic back pain. The additional therapy of risedronate with elcatonin may be a useful and practical choice for the treatment of osteoporosis with chronic back pain persisting more than 3 months. PMID- 25123563 TI - Characteristics of patients with yellow nail syndrome and pleural effusion. AB - Yellow nail syndrome (YNS) can be associated with a pleural effusion (PE) but the characteristics of these patients are not well defined. We performed a systematic review across four electronic databases for studies reporting clinical findings, PE characteristics, and most effective treatment of YNS. Case descriptions and retrospective studies were included, unrestricted by year of publication. We reviewed 112 studies (150 patients), spanning a period of nearly 50 years. The male/female ratio was 1.2/1. The median age was 60 years (range: 0-88). Seventy eight percent were between 41-80 years old. All cases had lymphoedema and 85.6% had yellow nails. PEs were bilateral in 68.3%. The appearance of the fluid was serous in 75.3%, milky in 22.3% and purulent in 3.5%. The PE was an exudate in 94.7% with lymphocytic predominance in 96% with a low count of nucleated cells. In 61 of 66 (92.4%) of patients, pleural fluid protein values were >3 g/dL, and typically higher than pleural fluid LDH. Pleurodesis and decortication/pleurectomy were effective in 81.8% and 88.9% of cases, respectively, in the treatment of symptomatic PEs. The development of YNS and PE occurs between the fifth to eighth decade of life and is associated with lymphoedema. The PE is usually bilateral and behaves as a lymphocyte-predominant exudate. The most effective treatments appear to be pleurodesis and decortication/pleurectomy. PMID- 25123565 TI - Evidence for a novel, local acute-phase response in the bovine oviduct: progesterone and lipopolysaccharide up-regulate alpha 1-acid-glycoprotein expression in epithelial cells in vitro. AB - Little is known about the local production and function of alpha 1-acid glycoprotein (AGP), an acute-phase protein, in the female reproductive tract. This study aimed to investigate the regulation and immune function of AGP in cultured bovine oviduct epithelial cells. Analysis by Western blotting and immunohistochemistry revealed that bovine oviduct tissue expresses AGP protein in epithelial cells and the smooth muscle layer. Stimulation of bovine oviduct epithelial cells in culture with either progesterone (1 ng/ml) or lipopolysaccharide (LPS, 10 ng/ml) induced both mRNA expression and secretion of AGP. Estradiol (1 ng/ml), progesterone (1 ng/ml), and luteinizing hormone (10 ng/ml), which are observed during the peri-ovulatory period in oviduct tissues (steroids) or in circulation (luteinizing hormone), suppressed LPS-induced expression and secretion of AGP, which in turn induced the expression of Toll like receptor-4 (TLR-4) and interleukin-1beta (IL-1B), but suppressed TLR-2 and tumor necrosis factor-alpha (TNFA) expression. AGP also inhibited LPS-induced TLR 2 and TNFA expression, but had no effect on LPS-induced TLR-4 and IL-1B expression. These findings suggest that oviductal epithelial cells can participate in antimicrobial processes through the secretion of AGP, which is partly regulated by ovarian steroids. Moreover, oviductal AGP may regulate the response of epithelial cells, thereby reducing the expression of the acute pro inflammatory cytokine TNFA, which could contribute to the local homeostasis during the acute response to endotoxin release in the oviduct's anti-infection process. PMID- 25123564 TI - Bedside ultrasound curriculum for medical students: report of a blended learning curriculum implementation and validation. AB - BACKGROUND: Medical students on clinical rotations rarely receive formal bedside ultrasound (BUS) training. We designed, implemented, and evaluated a standardized BUS curriculum for medical students on their Emergency Medicine (EM) rotation. Teaching was aimed toward influencing four cognitive and psychomotor learning domains: BUS instrumentation knowledge, image interpretation, image acquisition, and procedural guidance. METHODS: Participants viewed three instructional Web based tutorials on BUS instrumentation, the Focused Assessment for Sonography in Trauma (FAST) examination and ultrasound-guided central venous catheter (CVC) placement. Subsequently, participants attended a 3-hour hands-on training session to discuss the same content area and practice with faculty coaches. A Web-based, multiple-choice questionnaire was administered before and after the session. During the final week of the rotation, students returned for skills assessments on FAST image acquisition and CVC placement. RESULTS: Forty-five medical students on an EM rotation were enrolled. Sonographic knowledge overall mean score improved significantly from 66.6% (SD +/-11.2) to 85.7% (SD +/-10.0), corresponding to a mean difference of 19.1% (95% CI 15.5-22.7; p < 0.001). There were high pass rates for FAST (89.0%, 40/45) and CVC (96.0%, 43/45) skills assessments. There was no significant difference between medical student posttest and EM resident test scores 85.7% (SD +/-10.0) and 88.1% (SD +/- 7.6) (p = 0.40), respectively. CONCLUSIONS: A formal BUS curriculum for medical students on EM rotation positively influenced performance in several key learning domains. As BUS competency is required for residency in EM and other specialties, medical schools could consider routinely incorporating BUS teaching into their clinical rotation curricula. PMID- 25123566 TI - Progression of plasma D-dimer concentration and coagulopathies during hospitalization in horses with colic. AB - OBJECTIVE: To assess the progression of plasma D-dimer concentrations and coagulation status in horses with different types of colic. DESIGN: Prospective clinical observational study performed between March 2004 and September 2008. SETTING: Veterinary university teaching hospital. ANIMALS: Horses admitted and treated for colic and hospitalized for >48 hours were considered. Animals were classified by diagnosis into medical obstructive conditions (MO), surgical obstructive conditions (SO), inflammatory conditions, and ischemic lesions (IS). INTERVENTIONS: Three blood samples were obtained from each horse (admission, at 24-48 h [or after surgery] and upon discharge). For each sample, plasma D-dimer concentration, prothrombin time, activated partial thromboplastin time, antithrombin activity, and the presence of subclinical disseminated intravascular coagulation were determined. MEASUREMENTS AND MAIN RESULTS: When median plasma D dimer concentration values at admission and after 24-48 hours were compared, they were different but stable in horses with MO (1.29-1.95 nmol/L) and inflammatory conditions (5.70-6.69 nmol/L). However, 10-fold and 5-fold increases were observed, respectively, in SO (2.08 to 16.38 nmol/L) and IS (3.08 to 15.91 nmol/L) in the postoperative period. By 24-48 hours, the percentage of horses with coagulopathy increased in most groups (MO, 43 to 58%; SO, 50 to 96%, IS, 53 to 90%). By the time of discharge, 87% of horses with SO problems and 89% of horses with IS still had some form of coagulopathy documented. CONCLUSIONS: Throughout hospitalization, horses with MO problems had less severe coagulopathy and lower plasmatic D-dimer concentrations compared to other groups of horses. On admission, most horses with inflammatory conditions presented with coagulopathy. At 24-48 hours of hospitalization and following surgery, the hemostatic profile can differ markedly when compared to admission values. PMID- 25123567 TI - Chronic cutaneous chest wall fistula and gallstone empyema due to retained gallstones. AB - We report a case of a 72-year-old man who presented with a persistent pleural effusion and painful abscess in the right lower chest wall 6 months following a laparoscopic cholecystectomy. The patient subsequently developed a chronic cutaneous chest wall fistula requiring a large resection and complex closure. The complication was likely secondary to intraoperative spillage of gallstones. While previous reports describe gallstone spillage in the abdominal cavity as benign, this case illustrates that stones left in the abdominal cavity can potentially lead to significant morbidity. Therefore, stones should be diligently removed from the abdominal cavity when spillage occurs. In addition, it is important that operative notes reflect the occurrence of stone spillage so stones may be suspected when a patient presents with an abdominal or thoracic infection following a cholecystectomy. PMID- 25123568 TI - A rapidly growing lid lump. AB - A 97-year-old woman presented with a 5-month history of a rapidly growing, painless, left upper eyelid lesion. Examination revealed a large vascularised, ulcerated nodule on the left upper lid, causing significant ptosis. Wide local excision of the lesion was performed and the wound was left to heal by secondary intention. Histology and immunohistochemistry of the lesion confirmed a diagnosis of Merkel cell carcinoma, a rare primary malignancy of the eyelid which has significant morbidity and mortality. Although uncommon, this diagnosis should always be considered in any patient with a rapidly growing lid lump. In view of the patient's age, known dementia and family wishes, the patient was managed conservatively, with no further investigations performed. She was due to be followed up in clinic on a regular basis, but has since died from other causes. PMID- 25123569 TI - Septic sacroiliitis revealing an infectious endocarditis. AB - We report the case of a 43-year-old man admitted for right hip ache and fever. Physical examination revealed a fever, an ache at the manipulation of the sacroiliac joint and a limitation of abduction and external rotation of the right hip. There was no murmur in cardiac auscultation. No anomaly was found at the conventional radiographs of the sacroiliac joint, while the pelvic MRI confirmed a right sacroiliitis. A sacroiliac puncture with a study of synovial fluid demonstrated the presence of Streptococcus viridans. The blood culture revealed the same germ. Transthoracic and transoesophageal echocardiography confirmed infectious endocarditis with vegetation in the mitral valve. He received penicillin G and gentamicin relayed by pristinamycin because of an allergy to penicillin G with a total duration of treatment of 40 days. His symptoms and the laboratory and radiological tests abnormalities resolved totally with no recurrence. PMID- 25123570 TI - West-African trypanosomiasis in a returned traveller from Ghana: an unusual cause of progressive neurological decline. AB - West-African trypanosomiasis caused by Trypanosoma brucei gambiense is a rare imported infection presenting with somnolence, lymphadenopathy and wide-ranging neurological symptoms. A 67-year-old Caucasian man presented with a 10-month history of cognitive deterioration, ataxic gait, somnolence and urinary incontinence. His symptoms had progressed more rapidly over the course of a month prior to admission. Serological testing confirmed a diagnosis of West-African trypanosomiasis. The patient was successfully treated with eflornithine and made a good recovery. West-African trypanosomiasis should be considered in the differential diagnosis of unexplained cognitive decline in those with a relevant travel history. If left untreated, the condition is universally fatal. PMID- 25123571 TI - Isolated III cranial nerve palsies may point to primary histiocytic sarcoma. AB - Primary histiocytic sarcoma (HS) of the central nervous system (CNS) is a rare haematopoietic neoplasm. The inconsistent terminology and diagnostic criteria currently used for CNS HS have complicated the appreciation of the clinical aspects of the disease. The main differential diagnoses are non-Hodgkin's lymphoma, reactive histiocytic proliferation, dendritic cell neoplasm, undifferentiated carcinoma, inflammatory pseudotumour, Rosai-Dorfman disease and abscess. The true diagnosis of CNS HS requires an extensive immunophenotypic workup using specific histiocytic markers, such as CD163, with the exclusion of markers of other cell lineages. This clinicopathological case report describes an improved approach towards the differential diagnosis of CNS HS. PMID- 25123572 TI - Oral manifestation of plantar-palmar fibromatosis. PMID- 25123573 TI - Perivascular epithelioid cell tumour of the bladder. AB - A 39-year-old woman presented with a long history of pelvic pain and urinary urgency. Prior workup by her primary care doctor had been negative. The patient's gynaecologist ultimately referred her to a urologist following an ultrasound that revealed a possible bladder mass. MRI of the abdomen and pelvis demonstrated a 4 cm soft tissue lesion arising from the bladder. Cystoscopy showed an atypical mass on the anterior bladder wall, and pathological examination of the TURBT (transurethral resection of the bladder tumour) specimen revealed a perivascular epithelioid cell tumour (PEComa) with involvement of the detrusor muscle. The patient underwent a robotically assisted laparoscopic partial cystectomy. Final pathology confirmed a PEComa with negative margins. The patient had an uncomplicated postoperative course and is doing well following surgery. A surveillance cystoscopy at 6 months showed no evidence of recurrence. This case underscores the variability of clinical presentation of PEComas while proposing an appropriate method of surgical management. PMID- 25123574 TI - NK/T-cell non-Hodgkin's lymphoma with secondary haemophagocytic lymphohistiocytosis treated with matched unrelated donor allogeneic stem cell transplant. PMID- 25123576 TI - Colorectal cancer screening in the American Indian/Alaska Native population: progress and at least one new challenge. PMID- 25123575 TI - Activity of T-DM1 in HER-2 positive central nervous system breast cancer metastases. AB - A 55-year-old woman with metastatic human epidermal growth factor receptor 2 (HER 2) positive breast cancer (BC) to the lungs and bones was diagnosed with central nervous system (CNS) metastases in November 2011. The MRI showed a right parietal lobe mass with adjacent leptomeningeal disease and several small bilateral cerebellar metastases. She was treated with whole brain irradiation (WBI), followed by capecitabine and lapatinib (December 2011-March 2013) and trastuzumab and lapatinib (May 2013-August 2013). Then, the brain MRI showed progression. In the absence of significant neurological symptoms, we postponed WBI and closely monitored for the development of neurological symptoms. Systemic treatment with trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab, was initiated in September 2013 to control systemic disease. Unexpectedly, after two cycles of treatment the brain MRI showed a decrease in size of CNS metastases. This case report suggests possible activity of T-DM1 in HER-2 positive BC with CNS metastases. PMID- 25123578 TI - Differentiation and morphogenesis of the ovary and expression of gonadal development-related genes in the protogynous hermaphroditic ricefield eel Monopterus albus. AB - The ovarian differentiation, morphogenesis and expression of some putative gonadal development-related genes were analysed in the ricefield eel Monopterus albus, a protogynous hermaphroditic teleost with a single elongate ovary. At c. 1 day post-hatching (dph), the gonadal ridge was colonized with primordial germ cells (PGCs) at the periphery and transformed into the gonadal primordium, which appeared to contain two germinal epithelia. At c. 7 dph, four ovarian cavities appeared in the gonadal tissue with two in each germinal epithelial compartment, and the indifferent gonad might have begun to differentiate into the ovary. The oocytes at the leptotene stage in meiosis I appeared at c. 14 dph, and oocytes at the diplotene stage at c. 30 dph. As development proceeded, the connective tissue separating the two germinal epithelia disappeared, and two of the four ovarian cavities collapsed into one. At 60 dph, the gonad had already taken the shape as observed in the adults. One outer and two inner ovarian cavities could be easily recognized, with slightly basophilic primary growth oocytes usually residing close to the outer ovarian cavity. The expression of cyp19a1a and erb in the early gonad was detected at 6 dph. The abundant expression of foxl2 coincided with the up-regulation of cyp19a1a at 8 dph onwards. The expression of dmrt1 isoforms was not detectable until 8 dph for dmrt1a and dmrt1b and until 33 dph for dmrt1d. The earlier appearance of cyp19a1a compared to dmrt1 transcripts in the indifferent gonad may contribute to the initial differentiation of the gonad towards the ovary in M. albus. PMID- 25123577 TI - Neural tube defects and atypical deletion on 22q11.2. AB - The 22q11.2 deletion syndrome (22q11.2DS) is a common microdeletion disorder. Most of the patients show the common 3 Mb deletion but proximal 1.5 Mb deletion and unusual deletions located outside the common deleted region, have been detected particularly with the advance of comparative cytogenomic microarray technologies. The individuals reported in the literature with unusual deletions involving the 22q11 region, showed milder facial phenotypes, decreased incidence of cardiac anomalies, and intellectual disability. We describe two sibs with an atypical 0.8 Mb microdeletion of chromosome 22q11 who both showed myelomeningocele and mild facial dysmorphisms. The association between neural tube defect and the clinical diagnosis of Di George anomaly/velocardiofacial syndrome is well documented in the literature, but not all cases had molecular studies to determine breakpoint regions. This report helps to narrow a potential critical region for neural tube defects associated with 22q11 deletions. PMID- 25123579 TI - Risks of a lifetime in construction. Part II: Chronic occupational diseases. AB - BACKGROUND: We developed working-life estimates of risk for dust-related occupational lung disease, COPD, and hearing loss based on the experience of the Building Trades National Medical Screening Program in order to (1) demonstrate the value of estimates of lifetime risk, and (2) make lifetime risk estimates for common conditions among construction workers. METHODS: Estimates of lifetime risk were performed based on 12,742 radiographic evaluations, 12,679 spirometry tests, and 11,793 audiograms. RESULTS: Over a 45-year working life, 16% of construction workers developed COPD, 11% developed parenchymal radiological abnormality, and 73.8% developed hearing loss. The risk for occupationally related disease over a lifetime in a construction trade was 2-6 times greater than the risk in non construction workers. CONCLUSIONS: When compared with estimates from annualized cross-sectional data, lifetime risk estimates are highly useful for risk expression, and should help to inform stakeholders in the construction industry as well as policy-makers about magnitudes of risk. PMID- 25123581 TI - Pseudoporphyria following self-medication with chlorophyll. AB - Two cases of pseudoporphyria are described in which the clinical features of porphyria cutanea tarda occurred in the absence of abnormalities in porphyrin metabolism. Both patients presented with skin fragility and bullae on the dorsal aspect of the hands. The patients consumed a commercial liquid chlorophyll drink in which we detected fluorescent compounds with characteristics typical of previously described chlorophyll derived photosensitisers. PMID- 25123582 TI - Interaction of a novel antimicrobial peptide isolated from the venom of solitary bee Colletes daviesanus with phospholipid vesicles and Escherichia coli cells. AB - The peptide named codesane (COD), consisting of 18 amino acid residues and isolated from the venom of wild bee Colletes daviesanus (Hymenoptera : Colletidae), falls into the category of cationic alpha-helical amphipathic antimicrobial peptides. In our investigations, synthetic COD exhibited antimicrobial activity against Gram-positive and Gram-negative bacteria and Candida albicans but also noticeable hemolytic activity. COD and its analogs (collectively referred to as CODs) were studied for the mechanism of their action. The interaction of CODs with liposomes led to significant leakage of calcein entrapped in bacterial membrane-mimicking large unilamellar vesicles made preferentially from anionic phospholipids while no calcein leakage was observed from zwitterionic liposomes mimicking membranes of erythrocytes. The preference of CODs for anionic phospholipids was also established by the blue shift in the tryptophan emission spectra maxima when the interactions of tryptophan-containing COD analogs with liposomes were examined. Those results were in agreement with the antimicrobial and hemolytic activities of CODs. Moreover, we found that the studied peptides permeated both the outer and inner cytoplasmic membranes of Escherichia coli. This was determined by measuring changes in the fluorescence of probe N-phenyl-1-naphthylamine and detecting cytoplasmic beta-galactosidase released during the interaction of peptides with E. coli cells. Transmission electron microscopy revealed that treatment of E. coli with one of the COD analogs caused leakage of bacterial content mainly from the septal areas of the cells. PMID- 25123583 TI - Quantitative and qualitative morphologic, cytochemical, and ultrastructural characteristics of blood cells in captive Asian water monitors. AB - BACKGROUND: The Asian water monitor (Varanus salvator) is the most common monitor lizard in Thailand. Reported data regarding hematology and morphology of blood cells for this species are scarce. OBJECTIVES: The objective of this study was to assess routine hematologic variables and characterize the morphology, cytochemical staining, and ultrastructural features of blood cells in the Asian water monitor. METHODS: Blood samples from 55 monitors (22 males and 33 females) were obtained for a CBC. Cytochemical staining (Sudan black B [SBB], peroxidase [PO], alpha-naphthyl acetate esterase [ANAE], and beta-glucuronidase [BG]), and scanning and transmission electron microscopy were performed using standard methods. RESULTS: Determined mean (range) hematologic results of all monitors included PCV 0.32 L/L (0.20-0.44 L/L), HGB 106 g/L (62-157 g/L), WBC 15.9 * 10(9) /L (4.0-34.0 * 10(9) /L), heterophil 6.3 * 10(9) /L (1.5-17.1 * 10(9) /L, azurophil 2.6 * 10(9) /L (0.7-9.5 * 10(9) /L), basophil 0.1 (0.1-0.5 * 10(9) /L), lymphocyte 6.8 * 10(9) /L (0.5-13.1 * 10(9) /L), and monocyte 0.2 * 10(9) /L (0.04-1 * 10(9) /L) counts. Heterophils and basophils stained strongly positive with SBB, ANAE, and BG. Heterophils contained 2 types of granules, round SBB positive and PO-negative granules, and electron-dense, large rod-shaped granules. Gamonts of Hepatozoon sp. were found in <1% RBC of 43 monitors. There was no significant difference between hematologic variables in Hepatozoon-positive and negative monitors. CONCLUSION: Heterophils in Asian water monitors may also function as eosinophils based on cytochemical and ultrastructural features. The quantitative results may be used as base for further studies in healthy and diseased Asian water monitors. PMID- 25123584 TI - Revaluation of geometric cues reduces landmark discrimination via within-compound associations. AB - Rats were trained in a triangular water maze in which a compound of geometric and landmark cues indicated the position of a submerged platform. Rats that then underwent revaluation of the geometric cues in the absence of the landmarks subsequently failed to discriminate between the landmarks. In contrast, those animals that received geometry training consistent with their previous experience of the geometry-landmark compound continued to discriminate the landmark cues. The experiment showed that within-compound associations had formed between the geometry and landmarks, and that representations of absent geometric cues could be evoked via presentation of the landmark cues alone. We argue that these evoked representations of the absent geometry cues can counteract any overshadowing of the landmark by geometry cues, and may sometimes result in potentiation. The results of this study do not support theories of cue-competition failure based on independent cue processing, but remain readily explicable by appeal to an account based on within-compound associations. PMID- 25123585 TI - Thermal conductivity improvement of surface-enhanced polyetherimide (PEI) composites using polyimide-coated h-BN particles. AB - In this study, we investigated the thermal conductivities and mechanical properties of polyetherimide (PEI) composites using polyimide (PI)-coated h-BN (PI-BN) particles. We found that PI-coated h-BN effectively increased adhesion with the PEI matrix, imparting enhanced mechanical and thermal stability and thermal conductivity with increasing BN content. The thermal conductivity of the PEI composite containing 60 wt% PI-BN was 3.3 W m(-1) K(-1), while the thermal conductivity of the PEI/BN composite without modification was 2.6 W m(-1) K(-1). The PEI/PI-BN composites show higher impact strengths than the PEI/BN composites because of less BN particle agglomeration and good wettability between PEI and h BN. The results indicate that the PI-coated BN incorporated into the PEI matrix effectively enhances the thermal conductivity and mechanical properties of the PEI composites. PMID- 25123587 TI - Techniques to measure sorption and migration between small molecules and packaging. A critical review. AB - The mass transfer parameters diffusion and sorption in food and packaging or between them are the key parameters for assessing a food product's shelf-life in reference to consumer safety. This has become of paramount importance owing to the legislations set by the regulated markets. The technical capabilities that can be exploited for analyzing product-package interactions have been growing rapidly. Different techniques categorized according to the state of the diffusant (gas or liquid) in contact with the packaging material are emphasized in this review. Depending on the diffusant and on the analytical question under review, the different ways to study sorption and/or migration are presented and compared. Some examples have been suggested to reach the best possible choice, consisting of a single technique or a combination of different approaches. PMID- 25123588 TI - Mechanochromic luminescence of fluorenyl-substituted ethylenes. AB - It has been reported several times that some organic luminogens with aggregation induced emission (AIE) characteristics exhibit the abnormal phenomenon of crystallization-induced blueshift fluorescence, which makes them suitable for utilization as luminescence color-switching materials. Because of the attractive application potential and the numerous underlying structure-property relationships in such materials, we investigated a series of fluorenyl-containing tetrasubstituted ethylenes for their novel optical properties and structural features. The dyes show morphology-dependent luminescence. Their emission color can be switched between green and blue by means of mechanical grinding and solvent fuming. The transformation between crystalline and amorphous accounts for the luminescence changing. Through single-crystal and X-ray diffraction (XRD) analysis, the twisted molecular geometries and loose packing motifs in the crystalline samples are believed to be the intrinsic origin of the external stimuli-induced structural transformation. PMID- 25123586 TI - High-resolution crystal structure and IgE recognition of the major grass pollen allergen Phl p 3. AB - BACKGROUND: Group 2 and 3 grass pollen allergens are major allergens with high allergenic activity and exhibit structural similarity with the C-terminal portion of major group 1 allergens. In this study, we aimed to determine the crystal structure of timothy grass pollen allergen, Phl p 3, and to study its IgE recognition and cross-reactivity with group 2 and group 1 allergens. METHODS: The three-dimensional structure of Phl p 3 was solved by X-ray crystallography and compared with the structures of group 1 and 2 grass pollen allergens. Cross reactivity was studied using a human monoclonal antibody which inhibits allergic patients' IgE binding and by IgE inhibition experiments with patients' sera. Conformational Phl p 3 IgE epitopes were predicted with the algorithm SPADE, and Phl p 3 variants containing single point mutations in the predicted IgE binding sites were produced to analyze allergic patients' IgE binding. RESULTS: Phl p 3 is a globular beta-sandwich protein showing structural similarity to Phl p 2 and the Phl p 1-C-terminal domain. Phl p 3 showed IgE cross-reactivity with group 2 allergens but not with group 1 allergens. SPADE identified two conformational IgE epitope-containing areas, of which one overlaps with the epitope defined by the monoclonal antibody. The mutation of arginine 68 to alanine completely abolished binding of the blocking antibody. This mutation and a mutation of D13 in the predicted second IgE epitope area also reduced allergic patients' IgE binding. CONCLUSION: Group 3 and group 2 grass pollen allergens are cross-reactive allergens containing conformational IgE epitopes. They lack relevant IgE cross reactivity with group 1 allergens and therefore need to be included in diagnostic tests and allergen-specific treatments in addition to group 1 allergens. PMID- 25123589 TI - An exploration of compassion focused therapy following acquired brain injury. AB - BACKGROUND: People with acquired brain injuries (ABI) frequently experience psychological difficulties such as anxiety and depression, which may be underpinned and maintained by high self-criticism and shame alongside an inability to self-soothe. Compassionate focused therapy (CFT) was developed to address shame and self-criticism and foster the ability to self-soothe. OBJECTIVES: This is a naturalistic evaluation with the aim of assessing the feasibility, safety, and potential value of CFT for ABI patients with emotional difficulties receiving neuropsychological rehabilitation. METHODS: This study employed a mixed methods design combining self-report measures and qualitative interviews. Twelve patients received a combination of CFT group and individual intervention. Self-report measures of self-criticism, self-reassurance, and symptoms of anxiety and depression were collected pre and post programme and analysed using Wilcoxon signed rank test (N=12; five female, seven males). Follow up data were analysed in the same manner (N=9). Interviews were conducted with six patients and analysed using interpretative phenomenological analysis. RESULTS: CFT was associated with significant reductions in measures of self criticism, anxiety, and depression and an increase in the ability to reassure the self. No adverse effects were reported. Three superordinate themes emerged from the interviews: psychological difficulties; developing trust and finding safeness; and a new approach. CONCLUSIONS: This study suggests that CFT is well accepted in ABI survivors within the context of neuropsychological rehabilitation. Furthermore, the results indicate that further research into CFT for psychological problems after ABI is needed and that there may be key aspects, which are specific to CFT intervention, which could reduce psychological difficulties after ABI. PRACTITIONER POINTS: CFT appears to be a feasible intervention for psychological problems after ABI. CFT was associated with a reduction in symptoms of anxiety and depression and associated self-criticism, as well as enhanced self-reassurance for ABI survivors. These ABI survivors reported that CFT provided them with tools to manage continued psychological difficulties. PMID- 25123590 TI - Purification and biochemical characterization of an extracellular endoglucanase from the necrotrophic oomycete, Pythium myriotylum Dreschler. AB - An extracellular endoglucanase (EG) that catalyzes the hydrolysis of carboxy methyl cellulose (CMC) as substrate was purified to homogeneity from the soft-rot causing oomycete P. myriotylum with maximum EG production observed in presence of 1% (w/v) sucrose. The enzyme designated PmEG was observed to be monomeric with a molecular weight of 78 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Optimal activity of PmEG was determined at pH 5.0 and 25 degrees C with stability observed at pH extending over acidic to alkaline ranges viz., 3.0-10.0 and thermal stability upto 75 degrees C for 1 h. Optimal PmEG activity was obtained by addition of metal ions viz., Ca(2+) , Fe(3+) , Zn(2+) , Cu(2+) , Al(3+) , and also in presence of DTT and beta-mercaptoethanol while it was inhibited by Cr(2+) . Various organic solvents, surfactants, and the oxidant, H2 O2 had little/no effect on PmEG activity reflecting its robustness and potential commercial significance. Kinetic constants of PmEG, Km and Vmax were determined as 1.1 mM and 407 umol min(-1) mg(-1) protein, respectively. Glucose was observed to cause mixed non-competitive inhibition of PmEG. PMID- 25123591 TI - Unexpected drastic decrease in the excited-state electronic communication between porphyrin chromophores covalently linked by a palladium(II) bridge. AB - A dyad built up of a zinc(II) porphyrin and the corresponding free base, [Zn-Fb], fused to N-heterocyclic carbene (NHCs) ligands, respectively acting as singlet energy donor and acceptor, and a bridging trans-PdI2 unit, along with the corresponding [Zn-Zn] and [Fb-Fb] dimers were prepared and investigated by absorption and emission spectroscopy and density functional computations. Despite favorable structural and spectroscopic parameters, unexpectedly slow singlet energy transfer rates are measured in comparison with the predicted values by the Forster theory and those observed for other structurally related dyads. This observation is rationalized by the lack of large molecular orbital (MO) overlaps between the frontier MOs of the donor and acceptor, thus preventing a double electron exchange through the trans-PdI2 bridge, and by an electronic shielding induced by the presence of this same linker preventing the two chromophores to fully interact via their transition dipoles. PMID- 25123592 TI - Boosting the power conversion efficiency of perovskite solar cells using self organized polymeric hole extraction layers with high work function. AB - A self-organized hole extraction layer (SOHEL) with high work function (WF) is designed for energy level alignment with the ionization potential level of CH3 NH3 PbI3 . The SOHEL increases the built-in potential, photocurrent, and power conversion efficiency (PCE) of CH3 NH3 PbI3 perovskite solar cells. Thus, interface engineering of the positive electrode of solution-processed planar heterojunction solar cells using a high-WF SOHEL is a very effective way to achieve high device efficiency (PCE = 11.7% on glass). PMID- 25123593 TI - Lessons from early clinical experience with the Afirma gene expression classifier. PMID- 25123594 TI - Estimation of regional cerebral blood flow using N-isopropyl-p-123I iodoamphetamine acquisition data from the lungs and brain. An improved non invasive technique. AB - AIM: Previously, we devised a method for estimating123I labeled N-isopropyl-p iodoamphetamine (123I IMP) arterial blood activity at 10 minutes after intravenous injection of 123I IMP (Ca10) without any blood sampling using 123I IMP autoradiography (ARG) acquisition data, and verified its usefulness for quantification of regional cerebral blood flow (rCBF). In this study, we attempted to develop an improved noninvasive method for estimating rCBF. PATIENTS, METHODS: 123I IMP studies with 23 patients and 15O-H2O positron emission tomography (PET) ARG studies with 20 patients were evaluated. Multiple regression analysis was used to estimate an integral of the arterial blood counts during the time after injection of 123I (?Ca) using parameters from the time series of the lung counts and brain counts as the explanatory variables and the fraction [brain single-photon emission computed tomography (SPECT) average count / the mean of rCBFs (mean CBF) measured by 15O-H2O PET ARG method] as the objective variable. RESULTS: The regression equation was as follows: Estimated ?Ca = (7.09*10-3 . Cb12) - (1.57*10-4 . CbpreSPECT) + (9.48*10-5 . CbpostSPECT) + (1.35*10-4 . L15) - (6.95*10-4 . L33) + (7.61*10-4 . L81) - (0.417), where Cb12: brain count at 12 minutes, Cbpre-SPECT: brain count before SPECT, Cbpost-SPECT: brain count after SPECT, L15, L33, and L81: lung count at 15, 33, and 81 seconds, respectively. The mean CBF values (ml/min/100g) calculated using the estimated ?Ca values more closely correlated with those measured by 15O-H2O PET ARG method (r = 0.833, p < 0.01) than those obtained by our previous method (r = 0.590, p < 0.01). CONCLUSION: The rCBFs obtained by this method approximated more accurately to the values measured by 15O-H2O PET ARG method than those obtained by our previous method. PMID- 25123595 TI - Monitoring, analysis, and correction of magnetic field fluctuations in echo planar imaging time series. AB - PURPOSE: To assess the utility of concurrent magnetic field monitoring for observing and correcting for variations in k-space trajectories and global background fields that occur in single-shot echo planar imaging (EPI) time series as typically used in functional MRI (fMRI). METHODS: Field monitoring was performed using an array of NMR field probes operated concurrently with series of single-shot EPI acquisitions from a static phantom. The observed fluctuations in field evolution were analyzed in terms of their temporal and spatial behavior at the field level as well as at the level of reconstructed image series. The potential to correct for such fluctuations was assessed by accounting for them upon image reconstruction. An indication of the number and relative magnitude of underlying effects was obtained via principal component analysis. RESULTS: Trajectory and global field variations were found to induce substantial image fluctuations. Global field fluctuations induced standard deviations in image intensity up to 31%. Fluctuations in the trajectory induced ghosting artifacts with standard deviations up to 2%. Concurrent magnetic field monitoring reduced the fluctuations in the EPI time series to a maximum of 1.2%. CONCLUSION: Concurrent magnetic field monitoring holds the potential to improve the net sensitivity of fMRI by reducing signal fluctuations unrelated to brain activity. PMID- 25123596 TI - Capillary-assisted fabrication of biconcave polymeric microlenses from microfluidic ternary emulsion droplets. AB - In this study, a simple capillary-based approach for producing biconcave polymeric microlenses with uniform size and shape from ternary emulsion droplets is presented. Monodisperse ternary emulsion droplets (0.6-4.0 nL) are produced which contain a photocurable segment of an acrylate monomer and two non-curable segments of silicone oil (SO) by using a microfluidic sheath-flowing droplet generator on a glass chip. The curvature radius of the interfaces separating the droplet segments, as well as the droplet size, and production rate can be flexibly varied by changing the flow conditions of the organic and aqueous phases. Subsequently, off-chip suspension photopolymerization yields non spherical polymeric microparticles with two spherical concave surfaces templated by two SO segments at random positions. By ultraviolet light irradiation of ternary droplets with two SO segments trapped by the interior wall of a cylindrical microcapillary (internal diameter: 130 MUm), biconcave microlenses can be produced with two spherical concave surfaces with a common lens axis. The produced lenses are suitable for use as optical diverging lenses. PMID- 25123597 TI - Survival and tolerability of liver radioembolization: a comparison of elderly and younger patients with metastatic colorectal cancer. AB - AIM: To evaluate the outcomes among elderly (>=70 years) and younger patients (<70 years) with liver-dominant metastatic colorectal cancer (mCRC) who received radioembolization (RE) as salvage therapy. METHODS: A retrospective review of 107 consecutive patients with unresectable mCRC treated with RE after failing first- and second-line chemotherapy. RESULTS: From 2002 to 2012, 44 elderly and 63 younger (<70 years) patients received RE. Patients had similar previous extensive chemotherapy and liver-directed interventions. Using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, either a stable or a partial radiographical response was seen in 65.8% of the younger compared with 76.5% of the elderly patients. RE was equally well tolerated in both groups and common procedure-related adverse events were predominantly grade 1-2 and of short duration. No significant difference was found with regard to overall median survival between younger [8.4 months; 95% confidence interval (CI) = 6.2-10.6] or elderly patients (8.2 months; 95% CI = 5.9-10.5, P = 0.667). The presence of extrahepatic disease at the time of RE was associated with a significantly worse median survival in both groups. CONCLUSION: Radioembolization appears to be as well tolerated and effective for the elderly as it is for younger patients with mCRC. Age alone should not be a discriminating factor for the use of radioembolization in the management of mCRC patients. PMID- 25123598 TI - RIST: a potent new combination therapy for glioblastoma. AB - Glioblastoma is a highly aggressive, common brain tumor with poor prognosis. Therefore, this study examines a new therapeutic approach targeting oncogenic and survival pathways combined with common chemotherapeutics. The RIST (rapamycin, irinotecan, sunitinib, temozolomide) and the variant aRIST (alternative to rapamycin, GDC-0941) therapy delineate growth inhibiting effects in established glioblastoma cell lines and primary cultured patient material. These combinations significantly decreased cell numbers and viability compared to inhibitors and chemotherapeutics alone with aRIST being superior to RIST. Notably, RIST/aRIST appeared to be apoptogenic evoked by reduction of anti-apoptotic protein levels of XIAP and BCL-2, with concomitant up-regulation of pro-apoptotic protein levels of p53 and BAX. The treatment success of RIST therapy was confirmed in an orthotopic mouse model. This combination treatment revealed significantly prolonged survival time and drastically reduced the tumor burden by acting anti proliferative and pro-apoptotic. Surprisingly, in vivo, aRIST only marginally extended survival time with tumor volumes comparable to controls. We found that aRIST down-regulates the microvessel density suggesting an insufficient distribution of chemotherapy. Further, alterations in different molecular modes of action in vivo than in vitro suggest, that in vivo RIST therapy may mimic the superior aRIST protocol's pro-apoptotic inhibition of pAKT in vitro. Of note, all substances were administered in therapeutically relevant low doses with no adverse side effects observed. We also provide evidence of the potential benefits of the RIST therapy in a clinical setting. Our data indicates RIST therapy as a novel treatment strategy for glioblastoma achieving significant anti-tumorigenic activity avoiding high-dose chemotherapy. PMID- 25123599 TI - A team fares well with a fair coach: Predictors of social loafing in interactive female sport teams. AB - The present research aimed to develop and test a theoretical model that links players' perceived justice of the coach to a more optimal motivational climate, which in turn increases players' team identification and cohesion, and results in lower levels of social loafing in female sport teams. Belgian elite female basketball, volleyball, and football players (study 1; N = 259; M(age) = 22.6) and Norwegian world-class female handball players (study 2; N = 110; M(age) = 22.8) completed questionnaires assessing players' perceived justice (distributive and procedural), motivational climate, team identification, team cohesion (task and social), and social loafing (perceived and self-reported). In both studies, confirmatory and exploratory path analyses indicated that perceived justice was positively related to a mastery climate (P < 0.05) and negatively to a performance climate (P < 0.05). In turn, a mastery climate was linked to increased levels of team identification (P < 0.05) and task cohesion (P < 0.05). Consequently, players' perceived and self-reported social loafing decreased (P < 0.05). The findings of both independent studies demonstrated the impact of coaches' fairness, and consequently, the motivational climate created by the coach on the optimal functioning of female sport teams. PMID- 25123600 TI - Weight changes in obese adults 6-months after discontinuation of double-blind zonisamide or placebo treatment. AB - We evaluated weight changes in obese patients at 6-months after they ended participation in a 12-month randomised controlled trial in which they received daily placebo, zonisamide 200 mg or zonisamide 400 mg, in addition to lifestyle counselling. Of the originally randomised 225 patients, 218 completed month-12 when study interventions were discontinued. For the 154 patients who returned for 6-month follow-up off-treatment, weight changes between month-12 and month-18 for placebo (n = 53), zonisamide 200 mg (n = 49) and zonisamide 400 mg groups (n = 52) were 0.5 kg [95% confidence interval (CI), -0.8 to 1.8; 0.7%], 1.5 kg (0.2 2.8; 1.6%; p = 0.26 vs. placebo) and 2.4 kg (1.1-3.7; 2.6%; p = 0.04 vs. placebo), respectively. Our results suggest that although zonisamide 400 mg daily for 12-months resulted in greater weight loss than with placebo, weight regain after discontinuation of interventions was greater in the zonisamide 400 mg group than placebo group. PMID- 25123601 TI - Different roles for p16(INK) (4a) -Rb pathway and INK4a/ARF methylation between adenocarcinomas of gastric cardia and distal stomach. AB - BACKGROUND AND AIM: The incidence of distal gastric adenocarcinoma has significantly decreased, but gastric cardia adenocarcinoma has been on the rise. Cardia adenocarcinoma might be a specific entity distinct from the carcinoma of the rest stomach. The aim was to explore putative differences in p16(INK) (4a) retinoblastoma (Rb) pathway and INK4a/ARF methylation between gastric cardia and distal adenocarcinomas. METHODS: Ninety-six cardia adenocarcinomas and 79 distal samples were analyzed for comparing p16(INK) (4a) -Rb expressions, INK4a/ARF deletion, and methylation using immunohistochemistry, polymerase chain reaction, and methylation-specific polymerase chain reaction. RESULTS: The expression of p16(INK) (4a) in cardia adenocarcinoma (43.2%) was significantly lower than in distal cases (75.0%, P < 0.05). As well, cardia adenocarcinoma showed lower expression of p14(ARF) compared with distal cases (34.1% vs 57.5%, P < 0.05). The incidence of p16(INK) (4a) deletion was 20.5% and 15.0%, while p14(ARF) deletion was 18.2% and 10.0% in cardia and distal adenocarcinomas, respectively, showing no significant differences between two entities. However, the incidences of p14(ARF) and p16(INK) (4a) methylation in cardia adenocarcinoma were significantly higher than in distal samples (p14(ARF) : 61.5% vs 43.6%; p16(INK) (4a) : 73.1% vs 51.3%, P < 0.05). INK4a/ARF methylations were more prevalent in poorly differentiated cardia carcinoma compared with poorly differentiated distal cases. CONCLUSIONS: There were differences in p16(INK) (4a) -Rb immunotypes and INK4a/ARF methylation between two entities, indicating that cardia adenocarcinoma may be different in cell proliferation, differentiation, and gene biomarkers compared with distal gastric adenocarcinoma. PMID- 25123602 TI - Automated lipid membrane formation using a polydimethylsiloxane film for ion channel measurements. AB - A black lipid membrane (BLM) is a powerful platform for studying the electrophysiology of cell membranes as well as transmembrane proteins. However, BLMs have disadvantages in terms of stability, accessibility, and transportability, which preclude their industrial applications. To resolve these issues, frozen membrane precursor (MP) was devised to improve the transportability and storability of BLMs. As described previously, MP is a storable and transportable platform that can be delivered to the point-of-use, where BLMs are automatically formed upon thawing at room temperature. However, MP has an inconsistent thinning-out time, ranging from 30 min to 24 h, as well as a low success rate of BLM formation (~27%), which make it undesirable for practical use. In our study, polydimethylsiloxane (PDMS) was introduced as a replacement for conventionally used Teflon film to control thinning-out time. As such, we used a PDMS thin-film, a porous-structured hydrophobic polymer, and squalene, a high viscosity solvent, to facilitate membrane formation, whereas the absorption rates of solvents were controlled to achieve consistent BLM formation time. We successfully reduced thinning-out time down to <1 h as well as enhanced the success rate of BLM formation to greater than 80%. Moreover, we demonstrated the feasibility of our platform for use in drug screening using gramicidin A and guanidine. PMID- 25123603 TI - Predictive value of apoptotic microparticles to mononuclear progenitor cells ratio in advanced chronic heart failure patients. AB - BACKGROUND: Acutely decompensated chronic heart failure (ADHF) is considered a life-threatening event. Despite contemporary treatment strategies of ADHF, frequent recurrent hospitalizations due to other cardiovascular reasons after discharge of patients from hospital occur. The objective of the study was to examine the prognostic value of circulating endothelial-derived apoptotic microparticles (EMPs) to mononuclear progenitor cells (MPCs) ratio for post discharge patients with clinical stabilization after ischemic ADHF. METHODS: We consecutively enrolled 136 patients (62 male) with coronary artery disease (CAD) admitted with a primary diagnosis of ADHF. All patients gave written informed consent for participation in the study. At baseline, all enrolled patients were hemodynamically stable and they had New York Heart Association (NYHA) III/IV classes of ischemic chronic heart failure (CHF). Observation period started at discharge from the hospital and was up to 3 years. Flow cytometry analysis for quantifying the number of EMPs and angiogenic MPCs was used. RESULTS: Calculated EMP to MPC ratios in survivor and dead patient cohort were 8.4 (95% CI=7.6-9.2) and 78.9 (95% CI=53.0-116.6), respectively (p=0.001). MPCs, EMPs, NYHA class, N terminal pro-brain natriuretic peptide (NT-proBNP) and increased NT-proBNP>30% within 24-84h of admission period remained statistically significant for all cause mortality, CHF-related death, and CHF-related rehospitalization, whereas left ventricular ejection fraction and high-sensitivity C-reactive protein for all variables did not. We found that the addition of EPMs to MPCs ratio to the ABC model (NT-pro-BNP, increased NT-pro-BNP>30%) improved the relative integrated discrimination indices by 19.6% for all-cause mortality, by 21.7% for CHF-related death, and by 19.5% for CHF-related rehospitalization. CONCLUSION: We demonstrated that EMP to MPC ratio is considered an important indicator of an imbalance between angiogenic and apoptotic responses with possible relation to cardiovascular outcomes in post-discharge patients with clinical stabilization after ischemic ADHF. PMID- 25123604 TI - Gender differences in the clinical features of hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations. AB - BACKGROUND: Although gender may be one of the important factors modifying phenotypic expression in hypertrophic cardiomyopathy (HCM), there has been little information on it. METHODS AND RESULTS: We investigated gender differences in the clinical features of HCM caused by cardiac myosin-binding protein C gene (MYBPC3) mutations. Sixty-one subjects (28 families) carrying MYBPC3 mutations were studied. Of the 61 subjects with MYBPC3 mutations, 50 patients including 23 female patients were phenotype-positive by echocardiography. Disease penetrance in subjects aged <=40 years old was 92% in males and 67% in females. Females showed delayed onset of left ventricular hypertrophy compared with males in subjects who were genotype-positive. Female patients were more symptomatic at diagnosis than were males (mean New York Heart Association class: 1.7+/-0.8 versus 1.2+/-0.4, p=0.012). From a longitudinal point of view by age, no significant gender difference in cardiovascular deaths or cardiovascular events was found. During the follow-up period after diagnosis of HCM (13+/-8 years), female patients who were phenotype-positive had significantly more frequent heart failure events than did phenotypically affected male patients (p=0.028). CONCLUSIONS: Although females with MYBPC3 mutations showed later onset of the disease, female patients were more symptomatic at diagnosis and had more frequent heart failure events once they had developed hypertrophy. PMID- 25123605 TI - The Equivalence of Remote Electronic and Paper Patient Reported Outcome (PRO) Collection. AB - Individual patient level Patient Reported Outcomes (PROs) are increasingly important in clinical practice. Web-based collection enables clinicians to remotely collect scores at regular intervals, away from the clinic setting. In this randomized crossover study, 47 patients, having undergone hip surgery, were allocated to two groups. Group 1 completed the web-based scores followed by the paper equivalents one week later; Group 2 completed the scores the other way around. The Intraclass Correlation Coefficient (ICC) for the Oxford Hip Score was 0.99, 0.98 to 0.99 (ICC, 95% CI) and the ICCs for the other scores were between 0.95 and 0.97. We conclude that remote ePRO collection using this web-based system reveals excellent equivalence to paper PRO collection of the Oxford Hip, McCarthy, UCLA and howRu scores. PMID- 25123606 TI - Knee joint biomechanics and neuromuscular control during gait before and after total knee arthroplasty are sex-specific. AB - The future of total knee arthroplasty (TKA) surgery will involve planning that incorporates more patient-specific characteristics. Despite known biological, morphological, and functional differences between men and women, there has been little investigation into knee joint biomechanical and neuromuscular differences between men and women with osteoarthritis, and none that have examined sex specific biomechanical and neuromuscular responses to TKA surgery. The objective of this study was to examine sex-associated differences in knee kinematics, kinetics and neuromuscular patterns during gait before and after TKA. Fifty-two patients with end-stage knee OA (28 women, 24 men) underwent gait and neuromuscular analysis within the week prior to and one year after surgery. A number of sex-specific differences were identified which suggest a different manifestation of end-stage knee OA between the sexes. PMID- 25123607 TI - Reply to letter to the editor on "Simultaneous bilateral total knee arthroplasty in octogenarians: can it be safe and effective?". PMID- 25123608 TI - Nurses' choice of clinical field in early career. AB - AIM: To investigate how undergraduate nursing students' perceived professional qualifications and job values relate to their choice of clinical field after graduation, particularly about employment in care of older people and psychiatric fields. BACKGROUND: In the light of greater demand for highly qualified nurses, it is important to understand how professional qualifications and job values relate to career choices. DESIGN: A quantitative longitudinal study of 290 undergraduate nursing students based on a questionnaire survey and register data. METHODS: Data were analysed by multinomial logistic regression analyses. The questionnaire was distributed to all undergraduate nursing students during the final semester of study at two university colleges in Norway (N = 411) to collect the students' perceived professional qualifications and job values (2001). Register data on clinical fields after graduation (2002-2006) were merged into the survey data in 2008 (Statistics Norway). RESULTS: The tendency among undergraduate nursing students to choose care of older people rather than general hospital care after graduation increases as their score on altruism decreases, but is not correlated with their score on theoretical knowledge. The tendency to choose psychiatric fields rather than general hospital care increases with an increasing score on perceived practical skills and decreases with an increasing score on perceived theoretical knowledge. CONCLUSION: The choice of clinical field after graduation correlates with undergraduate nursing students' perceived professional qualifications and job values. PMID- 25123609 TI - The decalog of long non-coding RNA involvement in cancer diagnosis and monitoring. AB - Long non-coding RNAs (lncRNAs) are transcripts without protein-coding capacity; initially regarded as "transcriptional noise", lately they have emerged as essential factors in both cell biology and mechanisms of disease. In this article, we present basic knowledge of lncRNA molecular mechanisms, associated physiological processes and cancer association, as well as their diagnostic and therapeutic value in the form of a decalog: (1) Non-coding RNAs (ncRNAs) are transcripts without protein-coding capacity divided by size (short and long ncRNAs), function (housekeeping RNA and regulatory RNA) and direction of transcription (sense/antisense, bidirectional, intronic and intergenic), containing a broad range of molecules with diverse properties and functions, such as messenger RNA, transfer RNA, microRNA and long non-coding RNAs. (2) Long non coding RNAs are implicated in many molecular mechanisms, such as transcriptional regulation, post-transcriptional regulation and processing of other short ncRNAs. (3) Long non-coding RNAs play an important role in many physiological processes such as X-chromosome inactivation, cell differentiation, immune response and apoptosis. (4) Long non-coding RNAs have been linked to hallmarks of cancer: (a) sustaining proliferative signaling; (b) evading growth suppressors; (c) enabling replicative immortality; (d) activating invasion and metastasis; (e) inducing angiogenesis; (f) resisting cell death; and (g) reprogramming energy metabolism. (5) Regarding their impact on cancer cells, lncRNAs are divided into two groups: oncogenic and tumor-suppressor lncRNAs. (6) Studies of lncRNA involvement in cancer usually analyze deregulated expression patterns at the RNA level as well as the effects of single nucleotide polymorphisms and copy number variations at the DNA level. (7) Long non-coding RNAs have potential as novel biomarkers due to tissue-specific expression patterns, efficient detection in body fluids and high stability. (8) LncRNAs serve as novel biomarkers for diagnostic, prognostic and monitoring purposes. (9) Tissue specificity of lncRNAs enables the development of selective therapeutic options. (10) Long non-coding RNAs are emerging as commercial biomarkers and therapeutic agents. PMID- 25123610 TI - Serum soluble toll-like receptor 2: a novel biomarker for systemic lupus erythematosus disease activity and lupus-related cardiovascular dysfunction. AB - AIM: To assess the serum levels of soluble toll-like receptor (sTLR2) as an endogenous negative regulator of TLR2 signaling in systemic lupus erythematosus (SLE) patients, to investigate the correlation between sTLR2 and SLE disease activity index (SELDAI), SLE-related cardiovascular risk factors and ventricular dysfunction and to evaluate the effect of different therapeutic regimens on serum sTLR2 levels. METHODS: Ninety-six SLE patients, along with 30 healthy controls, were enrolled in the study. Echocardiography measurements were performed. Serum levels of (sTLR2) were measured using enzyme-linked immunosorbent assay (ELISA). Serum lipid profiles, uric acid and creatinine were also detected. RESULTS: Mean serum levels of sTLR2 in SLE patients was 3.98 +/- 4.4 ng/mL, which was significantly decreased as compared with that of the control group (11.3 +/- 4.9 ng/mL; P < 0.0001). sTLR2 was negatively correlated with SELDAI, low-density lipoprotein (LDL) and left ventricular diastolic dysfunction. sTLR2 levels were increased in patients receiving hydroxychloroquine, statins and corticosteroids. CONCLUSION: Serum sTLR2 can attenuate disease activity and negatively impact left ventricular diastolic dysfunction and hypercholersterelemia in SLE patients. Statins, corticosteroids and chloroquine increase sTLR2 levels. PMID- 25123611 TI - Multisystemic toxoplasmosis associated with a type II-like Toxoplasma gondii strain in a New Zealand fur seal (Arctocephalus forsteri) from New South Wales, Australia. AB - We report the first confirmed case of toxoplasmosis in an Australian pinniped. Presence of Toxoplasma gondii DNA was detected in the brain of a free-ranging subadult New Zealand fur seal (Arctocephalus forsteri) with nonsuppurative meningoencephalitis, hypophysitis, posterior uveitis, retrobulbar cellulitis, and myocarditis associated with protozoan cysts and tachyzoites. The emaciated seal stranded moribund on a beach in northern Sydney in New South Wales. Histopathology coupled with specific immunohistochemistry and PCR assays confirmed the presence of T. gondii. The T. gondii sample (NZfs8825) identified in this study has an identical genotype as the type II (ToxoDB PCR-RFLP genotype #1) based on the direct sequencing and virtual RFLP of multilocus DNA markers including SAG1, 5'- and 3'-SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico. Direct sequencing of T. gondii B1 DNA marker from the T. gondii sample (NZfs8825) identified a type II-like strain, based on presence of non archetypal B1 gene polymorphisms previously reported as unique to Australia. This study suggests that T. gondii oocysts originating from mainland Australia, which has a large population of feral cats, may act as a disease threat to native marine fauna. Therefore, emerging toxoplasmosis in the Arctic has a relevant parallel in the Southern Ocean within Australian waters with yet unknown relevance to Antarctica. PMID- 25123612 TI - Susceptibility of chickens (Gallus gallus domesticus) to Trichinella patagoniensis. AB - Trichinella spp. is a genus of parasites that is widespread all over the world. In Argentina, T. spiralis was for years the only species involved in human and animal outbreaks. During the last decade, T. patagoniensis, a new Trichinella species, was discovered in Argentina. Up to now, this species has only been found in cougars (Puma concolor). Experimental infections in pigs, cats, mice and rats with this new genotype showed that cats and mice were the most susceptible hosts. The aim of the present work was to evaluate the susceptibility of chickens to infection with T. patagoniensis. In order to study the intestinal and muscular phase, and the histopathological changes, 27 Leghorn chickens were inoculated per os with 1000 muscle larvae of T. patagoniensis and were euthanized on days 4, 5, 6, 7, 11, 14, 21, 28 and 35. Adult worms of T. patagoniensis were recovered from the small intestine of chickens up to day 14p.i. Gross examination of small intestine showed a moderate congestive appearance. Microscopically, an inflammatory response with lymphocytes and eosinophils in lamina propria, slight hyperemia, oedema and some haemorrhagic areas were detected. Lesions observed in chickens were similar to those described in different animal species during the intestinal phase. No muscular larvae were recovered from the muscle samples. These results suggest that T. patagoniensis is not capable to complete its entire life cycle in chickens. PMID- 25123613 TI - Daily peer review of abnormal cervical smears in the assessment of individual practice as an additional method of internal quality control. AB - OBJECTIVE: An important internal quality control system used in the Cancer Prevention and Research Institute cytopathology laboratory in Florence is the peer review procedure, based on the review of all abnormal cytological smears which routinely emerge. Peer review is an important training opportunity for all cytologists, especially for those with less experience. This article shows the results of the peer review procedure. METHODS: Of the 63 754 Papanicolaou (Pap) smears screened in 2011, 1086 were considered to be abnormal [at least atypical squamous cells of undetermined significance (ASC-US+)] on primary screening (selected by a single cytologist) and were subjected to the peer review procedure. The overall performance of the laboratory's cytologists was evaluated using a multiple rater analysis and the comparison of each cytologist with the final diagnosis. Further, the agreement was assessed by means of Cohen's kappa and weighted kappa statistics. RESULTS: In general, a moderate/substantial level of agreement between the ten cytologists and the final diagnoses was evident. Kappa values for each reader compared with the final diagnosis ranged from 0.54 to 0.69. The overall kappa value was 0.62 [95% confidence interval (CI), 0.58 0.66] and overall weighted kappa value was 0.76 (95% CI, 0.74-0.79). The category specific agreement showed the lowest values for atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). CONCLUSION: In summary, peer review represents an important internal quality control in the evaluation and improvement of inter-observer agreement and of the functioning of the laboratory as a whole. Multi-head microscope sessions may improve particularly the reproducibility of borderline diagnoses and, above all, can be an important training contribution for cytologists. PMID- 25123615 TI - How would you recognise a good review? PMID- 25123614 TI - Calcified amorphous tumors (CATs) of the heart. AB - Intracavitary cardiac masses include neoplastic and nonneoplastic masses, which may share overlapping clinical symptomatology, physical examination findings, and or imaging characteristics. Definitive diagnosis of a cardiac mass is usually made on surgical excision and histological examination. In this article, we focus on one of the rare nonneoplastic cardiac mass, namely, calcified amorphous tumors. We present a series of three patients, an 80-year-old female who presented to the hospital for evaluation of a near syncope event, a 69-year-old female who presented for evaluation of palpitations, and a 60-year-old female who presented for evaluation of shortness of breath, who were found to have calcified amorphous tumors. We have also provided a relevant review of the literature on this topic. PMID- 25123617 TI - Falls in rural and remote community dwelling older adults: a review of the literature. AB - OBJECTIVE: Falls in older adults represent a significant challenge in Australia; however, the focus is often on urban-dwelling older adults. The aim of this review was to explore the literature on falls epidemiology and falls prevention interventions (FPI). DESIGN: A literature review was conducted searching Medline, Scopus, Social Sciences Citation Index, Google Scholar, Google and the Australian Institute of Health and Welfare publication catalogue. SETTING: Rural and remote Australia. PARTICIPANTS: Rural and remote community dwelling Australians aged 50 years and older. INTERVENTION: Literature review. MAIN OUTCOME MEASURES: Falls epidemiology and effective falls prevention interventions. RESULTS: Twenty references were identified: 14 related to falls epidemiology and 7 to FPI. No significant differences were found between rural, remote and major cities residents in relation to falls hospitalisation, falls mortality or fall-related injuries sustained. There are a wide assortment of health professionals and non health professionals who are involved in providing FPI in rural and remote Australia. However, there was limited information on the effectiveness of these interventions in influencing falls outcomes. CONCLUSION: Few studies explored falls and their prevention in rural and remote Australia. The limited literature on the topic suggests that a change in focus to one that utilises existing services and resources will be required to create sustainable outcomes. Four areas are proposed for concentrated effort to reduce the impact of fall-related injury in rural and remote Australia: integration and collaboration among health professionals, promotion of physical activity across the lifespan, community involvement and ownership of interventions, and evaluation and publication of findings. PMID- 25123618 TI - Timely access to specialist medical oncology services closer to home for rural patients: experience from the Townsville Teleoncology Model. AB - PROBLEM: Prior to 2009, the teleoncology model of the Townsville Cancer Centre (TCC) did not achieve its aims of equal waiting times for rural and urban patients and the provision of reliable, local acute cancer care. From 2007-2009, 60 new patients from Mt Isa travelled to TCC for their first consultation and their first dose of chemotherapy. Six of these patients required inter-hospital transfers and eight required urgent flights to attend outpatient clinics. Only 50% these rural patients (n = 30) were reviewed within one week of their referral, compared with 90% of Townsville patients. DESIGN: A descriptive study. SETTING: TCC provides teleoncology services to 21 rural towns; the largest is Mt Isa, Qld. KEY MEASURES FOR IMPROVEMENT: Specialist review of 90% of urgent cases within 24 hours, and 90% of non-urgent cases within one week of referral via videoconferencing. A 50% reduction in inpatient inter-hospital transfers from Mt Isa to Townsville. STRATEGIES FOR CHANGE: Employment of a half-time medical officer and a half-time cancer care coordinator, and implementation of new policies. EFFECTS OF CHANGE: Between 2009 and 2011, TCC provided cancer care to 70 new patients from Mt Isa. Of these new patients, 93% (65/70) were seen within one week of referral. All 17 patients requiring urgent reviews were seen within 24 hours of referral and managed locally thus eliminating the need for inpatient inter-hospital transfers. LESSONS LEARNT: Provision of timely acute cancer care closer to home requires an increase in the rural case complexity and human resources. PMID- 25123619 TI - Rural palliative care transitions from home to hospital: carers' experiences. AB - OBJECTIVE: To document carer perceptions of patients' transitions from community to hospital-based palliative care in a rural setting. DESIGN: A qualitative study using an interview method at two time points. SETTING: Rural palliative care providers: Kyneton District Health Service and the Macedon Ranges Palliative Care Service, Victoria. PARTICIPANTS: Six adult caregivers of six palliative care patients who had cancer were interviewed, three of whom were male and three female. MAIN OUTCOME MEASURES: Semistructured interviews were conducted exploring the caregivers' decisions to transition to hospital-based care and their perceptions of the transition to hospital and the hospital-based care these patients received. RESULTS: Thematic analysis revealed that carers made the decision for the patient in their care to transfer from home to hospital care. Carers experienced the transition to hospital care positively, particularly in relation to the communication of the patient's care needs. While communication issues arose while in hospital, they were not related to the transitional aspects of the palliative care service. CONCLUSIONS: The findings from this small, exploratory study suggest that these carers benefited from the new model of rural palliative care service provision. A large-scale, mixed-method study would enable more generalisable findings to be established. PMID- 25123620 TI - Predictors of rural practice location for James Cook University MBBS graduates at postgraduate year 5. AB - OBJECTIVE: To describe factors predicting James Cook University (JCU) medical graduates having a rural practice location at postgraduate year (PGY) 5. PARTICIPANTS: JCU MBBS graduates who had completed their PGY 5 in Australia (n = 260). DESIGN: Multiple logistic regression analysis involving graduates' application data (age, gender, location of hometown, School Leaving Score, interview score, ethnicity), undergraduate data (scholarship awarded, honours program), and postgraduation data (internship location, specialty training undertaken). MAIN OUTCOME MEASURE: Predictors of practice in a 'rural' town (Australian Standard Geographic Classification Remoteness Area (ASGC-RA)) 3-5 at PGY 5. RESULTS: Practice in a 'rural' town in PGY 5 was predicted by 'internship in an ASGC-RA 3-5 location' (prevalence odds ratios (POR) = 3.9, P < 0.001), 'undertaken postgraduate training as a general practitioner or rural generalist' (POR = 3.4, P < 0.001), 'hometown at application located in ASGC-RA 3-5 area' (POR = 2.9, P = 0.023), 'Aboriginal & Torres Strait Islander ancestry' (POR = 5.6, P = 0.031), and NOT undertaken postgraduate training in surgery (POR = 5.4, P = 0.055). CONCLUSIONS: This study provides evidence that likelihood of early career rural medical practice in Australia is enhanced by education strategies, such as providing rurally located internship places, supporting rural general practice, and selecting applicants with rural origins, Aboriginal or Torres Strait Islander ancestry, and/or a genuine interest in rural, remote, Indigenous, and tropical medicine. This early evidence supports the proposition that investing in rural medical education will produce an appropriately trained medical workforce to meet the needs of rural Australia. Findings also suggest rural workforce may be further enhanced with additional specialty training opportunities in rural tertiary hospitals, in particular, surgery. PMID- 25123621 TI - Undergraduate physiotherapy students' expectations and perceptions of rural/regional clinical placements. AB - OBJECTIVE: To explore undergraduate physiotherapy students' expectations and preconceptions of undertaking a rural/regional clinical placement and determine if these preconceptions differ between regional and metropolitan-based students. DESIGN: Data was collected via focus groups and analysed via thematic analysis of emerging themes. SETTING: All focus groups were undertaken in tutorial rooms at the participating universities between classes at a time convenient to participants. PARTICIPANTS: Undergraduate physiotherapy students yet to complete a major clinical placement were invited to participate. Second year physiotherapy students from regional and metropolitan universities were recruited to form focus groups, allowing comparison between the two groups. Four metropolitan students and nine regional students made up the sample size. RESULTS: Three major themes were identified via thematic analysis of transcripts; socio-cultural factors, education and professional factors. The significance of socio-cultural factors was far beyond what was expected to be found. Regional students did not generally have a more accurate perspective of rural/regional placement and voiced more concerns about missing out on educational opportunities. CONCLUSIONS: Rural/regional clinical educators need to be mindful of creating quality experiences with caseloads appropriate for the specific placement's requirements. The impact of external socio-cultural factors must be acknowledged. Supervision strategies must be put in place to ensure students on rural/regional clinical placements are well supported to achieve a successful outcome for student and educator. PMID- 25123622 TI - What is the impact of longitudinal rural medical student clerkships on clinical supervisors and hospitals? AB - OBJECTIVE: Studies have investigated the impact of medical students undertaking longitudinal clerkships in General Practices; however, little is known about the impact of students' longitudinal clerkships on clinical supervisors in the hospital environment. This research aimed to explore the educational impacts and benefits gained from supervisory responsibilities in a rural hospital context. DESIGN: We assessed the impact of longitudinal clerkships using individual and group-structured interviews. The responses were thematically analysed by the researchers. SETTING: Two rural hospitals in Victoria, Australia. PARTICIPANTS: Fifteen senior medical and nursing staff at two rural hospitals who supervised year four medical students in a longitudinal clinical program. RESULTS: Thematic analysis identified three major themes: changes to the supervisor, change in the hospital learning culture and student usefulness. Doctors and nurses who undertook student supervisory responsibilities reported a sense of personal change, including increased reflective practice, improved value of professional identity and increased enthusiasm for interprofessional learning. Supervisors updated their clinical skills and became proactive in seeking out learning opportunities for students. Hospitals became more vibrant learning environments and interprofessional education enhanced teamwork. Patient care increased, knowledge gaps filled and hospital governance, policy and procedures challenged. CONCLUSION: The benefits of longitudinal clerkship in the rural hospital setting provided symbiotic relationships between hospitals, students, patients and educations provider. The interprofessional approach towards clinical supervision enhanced supervisor learning and generated an understanding among professional groups of each other's clinical skills, roles and values, and raised an awareness of the importance of working collaboratively for better patient outcomes and addressing future workforce shortages. PMID- 25123623 TI - Bibliometric analysis on Australian rural health publications from 2006 to 2012. AB - OBJECTIVE: To review Australian rural health (ARH) publications in PubMed from 2006 to 2012 and address ARH issues raised by the 2013 Health and Medical Research report. DESIGN: Retrospective observational study. SETTING: Internet based bibliometric analysis using PubMed. MEDLINE-indexed ARH publications from 2006 to 2012 were retrieved using PubMed queries. ARH publications were defined as Australian publications that explore issues relevant to the health of the regional, rural or remote Australian population. Two authors independently reviewed a random sample of 5% of publications for validity. MAIN OUTCOME MEASURES: Analysis determined country of origin (Australia); publications relevant to the National Health Priority Areas, the 2013 National Rural Health Alliance priority areas and Rural Clinical Schools/University Departments of Rural Health; and journal frequencies and publication types. RESULTS: ARH publications increased from 286 in 2006 to 393 in 2012 and made up 1.4% of all Australian PubMed publications. Combined, the health priority areas were addressed in 52% of ARH publications. Rural Clinical Schools/University Departments of Rural Health articles made up 7% of ARH publications. An increase in cohort studies, systematic reviews and reviews indicated improved quality of articles. ARH articles were most commonly published in the Australian Journal of Rural Health (15.9%), Rural and Remote Health (13.4%) and the Medical Journal of Australia (6.3%). Striking a balance between broadening the queries (increasing sensitivity) and limiting the false positives by restricting the breadth of the queries (increasing specificity) was the main limitation. CONCLUSIONS: This reproducible analysis, repeated at given timelines, can track the progress of ARH publications and provide directions regarding future rural health research. PMID- 25123624 TI - Rural patients' experiences of the open disclosure of adverse events. AB - OBJECTIVE: To analyse rural patients' and their families' experiences of open disclosure and offer recommendations to improve disclosure in rural areas. DESIGN: Retrospective qualitative study based on a subset of 13 semistructured, in-depth interviews with rural patients from a larger dataset. The larger data set form a nationwide, multisite, retrospective-qualitative study that included 100 semistructured, in-depth interviews with 119 patients and family members who were involved in high-severity health care incidents and incident disclosure. The larger study is known as the '100 Patient Stories' study. Interviews were transcribed verbatim and analysed by one analyst (D.P.) for recurrent experiences and concerns. SETTING: Acute care. PARTICIPANTS: A sub-set of 13 of the 100 participants from the '100 Patient Stories' study who identified as experiencing an adverse incident in a rural or regional area. MAIN OUTCOME MEASURES: Patients' and family members' perceptions and experiences of health care incident disclosure, as expressed in interviews. RESULTS: Rural patients and clinicians experience additional challenges to metropolitan patients and clinicians in their experiences of health care incidents. These additional barriers include: a lack of resources at small hospitals; delays in diagnosis and transfer; distance between services; and a lack of communication between providers. These challenges impact not only upon how patients and their families experience incidents, but also how open disclosure is implemented. CONCLUSIONS: This analysis of 13 of the 100 Patient Stories interviews provides guidance to rural health services on how to conduct open disclosure. PMID- 25123625 TI - Creating positive rural experiences for occupational therapy students. PMID- 25123626 TI - DOT (directly observed therapy) in diabetes: current thought, future reality. PMID- 25123627 TI - Do clinical pathways enhance access to evidence-based acute myocardial infarction treatment in rural emergency departments? PMID- 25123628 TI - Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK pathway. AB - Understanding the mechanism by which alpha-lipoic acid supplementation has a protective effect upon nonalcoholic fatty liver disease in vivo and in vitro may lead to targets for preventing hepatic steatosis. Male C57BL/6J mice were fed a normal diet, high-fat diet or high-fat diet supplemented with alpha-lipoic acid for 24 weeks. HepG2 cells were incubated with normal medium, palmitate or alpha lipoic acid. The lipid-lowering effects were measured. The protein expression and distribution were analyzed by Western blot, immunoprecipitation and immunofluorescence, respectively. We found that alpha-lipoic acid enhanced sirtuin 1 deacetylase activity through liver kinase B1 and stimulated AMP activated protein kinase. By activating the sirtuin 1/liver kinase B1/AMP activated protein kinase pathway, the translocation of sterol regulatory element binding protein-1 into the nucleus and forkhead box O1 into the cytoplasm was prevented. Alpha-lipoic acid increased adipose triacylglycerol lipase expression and decreased fatty acid synthase abundance. In in vivo and in vitro studies, alpha-lipoic acid also increased nuclear NF-E2-related factor 2 levels and downstream target amounts via the sirtuin 1 pathway. Alpha-lipoic acid eventually reduced intrahepatic and serum triglyceride content. The protective effects of alpha-lipoic acid on hepatic steatosis appear to be associated with the transcription factors sterol regulatory element-binding protein-1, forkhead box O1 and NF-E2-related factor 2. PMID- 25123629 TI - From body shadows to bodily attention: automatic orienting of tactile attention driven by cast shadows. AB - Body shadows orient attention to the body-part casting the shadow. We have investigated the automaticity of this phenomenon, by addressing its time-course and its resistance to contextual manipulations. When targets were tactile stimuli at the hands (Exp.1) or visual stimuli near the body-shadow (Exp.2), cueing effects emerged regardless of the delay between shadow and target onset (100, 600, 1200, 2400ms). This suggests a fast and sustained attention orienting to body-shadows, that involves both the space occupied by shadows (extra-personal space) and the space the shadow refers to (own body). When target type became unpredictable (tactile or visual), shadow-cueing effects remained robust only for tactile targets, as visual stimuli showed no overall reliable effects, regardless of whether they occurred near the shadow (Exp.3) or near the body (Exp.4). We conclude that mandatory attention shifts triggered by body-shadows are limited to tactile targets and, instead, are less automatic for visual stimuli. PMID- 25123630 TI - Anhedonia in prolonged schizophrenia spectrum patients with relatively lower vs. higher levels of depression disorders: associations with deficits in social cognition and metacognition. AB - This study has sought to explore whether there are at least two subtypes of anhedonia in schizophrenia: one closely linked with depression and another that occurs in the absence of depression which is related to a general paucity of internal experience. Participants were 163 adults with schizophrenia who completed assessments of depression, anhedonia, executive functioning, positive and negative symptoms, social cognition and metacognition. A cluster analysis based on participants' depression and anhedonia symptom scores produced three groups: High Depression/High Anhedonia (n=52), Low Depression/Low Anhedonia (n=52), and Low Depression/High Anhedonia (n=59). An ANCOVA and post hoc comparisons controlling for positive and negative symptoms found that the Low Depression/High Anhedonia group had poorer metacognition and social cognition than other groups. These findings point to the possibility of a subtype of anhedonia in schizophrenia, one occurring in the relative lesser levels of depression, and tied to deficits in the ability to think about oneself and others. PMID- 25123631 TI - Multi-component reactive transport in heterogeneous media and its decoupling solution. AB - The multi-component reactive transport model is widely used in contaminant transport, water-rock interaction, and other earth science fields. Since its complexity lies in its solution, a decoupling approach is used to simplify the model to enhance computational efficiency. A decoupling approach is presented for heterogeneous media, and used to solve the model in this situation. The whole domain is divided into several sub-domains due to the different reactions which may occur and the corresponding component matrix was obtained. The boundary between sub-domains could be divided into two parts, inflow and outflow, which are defined as the Neumann condition and the Dirichlet one, and the concentration of the latter could be calculated by the component in the adjacent sub-domain. Then the models in each sub-domain can be connected and solved. Taking a heterogeneous porous media as an example in which permanganate is partially dissolved during the process, firstly the result obtained by this method without considering porosity variation is compared to that from PHAST: good agreement is achieved, then while considering the change of porosity caused by the dissolution of the permanganate, the flow field, species concentration and porosity of the whole domain and typical sections and points during the reaction are analysed. It is concluded that: the decoupling approach to heterogeneous media is appropriate, and the results from the model could reflect the variation of physical fields due to groundwater in heterogeneous media. PMID- 25123632 TI - Global gene expression profiling of porcine endometria on Days 12 and 16 of the estrous cycle and pregnancy. AB - The objective of the study was to investigate transcriptomic profile of pig endometrium on Days 12 and 16 of pregnancy in comparison with the respective days of the estrous cycle. Labeled complementary DNA was hybridized to Porcine Long Oligo microarray containing 13,297 oligonucleotide probes, which represented complementary DNA and expressed sequence tags. Statistical analysis revealed 110 differentially expressed genes (DEGs) on Day 12 of pregnancy and 179 DEGs on Day 16 of pregnancy. In silico analysis of gene function and functionality networks revealed links between genes implicated in cell death and survival, protein synthesis, lipid metabolism, cellular movement, tissue development, and cell-to cell signaling. On Day 12 of pregnancy, estrogen, transforming growth factor (TGF) beta1, and fibroblast growth factor (FGF) 2, and on Day 16 of pregnancy, epidermal growth factor (EGF), insulin, interleukin 11 (IL-11), and FGF family members were indicated as possible upstream regulators of several DEGs. Obtained results showed changes in global endometrial gene expression at the time of maternal recognition of pregnancy and embryo implantation. Additionally, these data revealed signaling molecules, which together with E2, may evoke molecular changes in the uterus, leading to successful pregnancy establishment. PMID- 25123633 TI - New method for assessing hand disinfection shows that pre-operative alcohol/chlorhexidine rub is as effective as a traditional surgical scrub. AB - BACKGROUND: Several studies have shown that rubbing hands with an alcohol/chlorhexidine solution provides equivalent microbial decontamination to a conventional surgical scrub using aqueous chlorhexidine. However, the authors believe that these studies have methodological flaws that limit their applicability to the operating theatre environment. As such, a method was developed to compare products in an everyday operating theatre environment using working operating theatre personnel. AIM: To determine whether or not an alcohol/chlorhexidine rub is as efficacious as a traditional surgical scrub using a novel method. METHODS: Bacterial counts at baseline were collected from 20 anaesthetists using the glove juice method. Subsequently, with sequential exchange of sterile gloves, one hand underwent a 3-min scrub using 4% aqueous chlorhexidine, and the other hand underwent a 60-s rub with a 70% isopropyl alcohol/0.5% chlorhexidine solution. The residual bacterial count was collected for each hand after 30 min using the glove juice method. These counts were converted to log10 values to compare the baseline counts of right and left hands, and efficacy between the treatment groups. FINDINGS: Mean [+/- standard deviation (SD)] bacterial counts at baseline were (log10) 4.42 +/- 0.81 for left hands and 4.64 +/- 0.60 for right hands (P > 0.05). The mean (+/- SD) reduction from baseline was (log10) 1.45 +/- 0.50 for 4% chlorhexidine and 2.01 +/- 0.98 for alcohol/chlorhexidine (P > 0.05). CONCLUSION: An alcohol/chlorhexidine hand rub was found to be as efficacious as a traditional scrub after 30 min; this study differs from previous work as it was undertaken in a population of practising anaesthetists in their working environment. The McKenzie method allows baseline and study evaluations to be performed contemporaneously on the same individual. Each subject was his/her own control. This method offers a more clinically relevant way to compare disinfectant solutions than standard methods. PMID- 25123634 TI - Risk factors for mediastinitis following cardiac surgery: the importance of managing obesity. AB - BACKGROUND: Mediastinitis is a devastating complication of cardiac surgery. Previous studies have often observed small populations, been retrospective in design, and used a variety of definitions for mediastinitis. AIM: To identify risk factors for mediastinitis, and strategies to minimize its incidence. METHODS: A prospective cohort study of 4883 adult patients who underwent cardiac surgery between October 2003 and February 2009, comparing pre- and peri-operative risk factors, microbial aetiology, requirement for re-admission, length of stay and mortality between patients with and without mediastinitis. FINDINGS: Ninety (1.8%) patients were diagnosed with mediastinitis. Microbial aetiology was defined for 75 patients. Staphlyocococcus aureus was the most common isolate (30 episodes; 15 due to meticillin-resistant S. aureus). Univariate analysis revealed the following pre-operative factors associated with mediastinitis: age; body mass index; diabetes; modified logistic European System for Cardiac Operative Risk Evaluation score; urgent admission; and longer pre-operative stay (P < 0.05). Associated peri-operative factors were: combined coronary artery bypass grafting plus aortic valve replacement; longer aortic cross-clamp time; and longer cardiopulmonary bypass time (P < 0.005). Multi-variate analysis revealed that higher body mass index, combined coronary artery bypass grafting plus aortic valve replacement, and older age were associated with mediastinitis (P < 0.05). Mediastinitis was associated with re-admission to hospital, longer inpatient stay and reduced long-term survival (P < 0.05). CONCLUSION: Mediastinitis is associated with worse short-term outcomes (re-admission, length of stay) and reduced long-term survival. Obesity is the only modifiable pre-operative risk factor for mediastinitis. It may be possible to reduce risk through pre-operative weight loss programmes before elective surgery. PMID- 25123635 TI - Randomized experimental study to investigate the peritoneal adhesion formation of conventional monopolar contact coagulation versus noncontact argon plasma coagulation in a rat model. AB - OBJECTIVE: To investigate peritoneal adhesion formation of monopolar contact coagulation (MCC) versus noncontact argon plasma coagulation (APC) in a rat model. DESIGN: Randomized, controlled, single-blinded animal study. SETTING: University laboratory. ANIMAL(S): Sixteen female Wistar rats. INTERVENTION(S): Bilateral lesions were created on the abdominal wall with MCC and APC in a standard fashion. After 10 days, the rats were euthanized to evaluate the peritoneal trauma sites. MAIN OUTCOME MEASURE(S): Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. RESULT(S): Average energy intake was 99.5 +/- 7.39 J for APC and 95.7 +/- 9.62 J for monopolar contact coagulation. Incidence of adhesion formation was 50.0% for noncontact APC and 85.4% for MCC. MCC induced significantly more vascular adhesions. Histological evaluation revealed no significant differences regarding average depth of lesions induced by APC and MCC. Both groups showed almost identical morphology of necrosis and granulation tissue formation. CONCLUSION(S): This study compares for the first time adhesion formation of MCC versus noncontact APC in a rat model. With a similar energy intake, contact coagulation induced a significantly higher rate of adhesion formation. APC-induced adhesions were significantly less vascularized compared with MCC adhesions. Besides the thermal effects of both coagulation methods, the direct mechanical contact of the MCC electrode with the highly sensitive peritoneum is thus determined to be a pivotal additional stimulus for adhesion formation. PMID- 25123636 TI - Is subfertility or fertility treatment associated with long-term growth in the offspring? A cohort study. AB - OBJECTIVE: To study whether fertility treatment or subfertility is associated with long-term growth in the offspring. DESIGN: A prospective follow-up study including 1,773 singletons participating in the Lifestyle During Pregnancy Study at the age of 5. SETTING: Research centers. PATIENT(S): A total of 3,478 mother child pairs were sampled from the Danish National Birth Cohort, and 1,773 completed the outcome measurements. A total of 69 children were born after fertility treatment, whereas 132 were born to subfertile parents conceiving spontaneously but after a time to pregnancy of more than 12 months. The remaining 1,572 children were born to parents conceiving spontaneously within 12 months. At the age of 5, the children participated in a follow-up including anthropometric measurements. Information on important covariates with respect to family background, maternal prenatal exposures, perinatal outcomes, and postnatal parental lifestyle characteristics were obtained from the Danish National Birth Cohort, the 5-year follow-up, and Danish health registers. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Adjusted mean differences in body weight, height, body mass index (BMI), and head circumference at age 5. RESULT(S): Compared with spontaneously conceived children born to fertile parents, no systematic differences were observed for body weight, height, BMI, or head circumference at age 5 in children conceived after fertility treatment or to subfertile parents conceiving spontaneously. CONCLUSION(S): There were no differences in child anthropometrics at 5 years between children conceived after fertility treatment or by subfertile parents compared with that of children born to fertile parents. However, children born after fertility treatment may show catch-up growth during childhood. PMID- 25123637 TI - Outcomes of primary surgical evacuation during the first trimester in different types of implantation in women with cesarean scar pregnancy. AB - OBJECTIVE: To assess the efficacy and safety of primary surgical evacuation therapy for cesarean scar pregnancy (CSP) of the first trimester, and to evaluate its possible prognostic factors. DESIGN: Retrospective consecutive cohort study. SETTING: Tertiary care university hospital. SUBJECT(S): A cohort of patients with CSP and clear ultrasound images who underwent primary surgical evacuation from January 2000 to December 2012. INTERVENTION(S): Patients fulfilling the ultrasound criteria of CSP were further classified into superficial and deep groups according to their implantation locations and extents. The final decision on the method of treatment, including methotrexate chemotherapy, surgical evacuation, and others, was made by the patients after consultation with the physician. Pretreatment patient characteristics were compared in the patients with superficial and deep implantation, as were the results after primary surgical evacuation. MAIN OUTCOME MEASURE(S): Rates of successful treatment by primary surgical evacuation of CSP and the need for salvage intervention in the patients with deep and superficial implantation. RESULT(S): Forty-eight CSP patients who had sufficient data and imaging for analysis were enrolled. Of these 48 cases, 26 in the superficial group and 14 in the deep group were willing to undergo primary surgical evacuation. Blood loss and need for salvage intervention were significantly lower in the patients with superficial implantation. Surgical evacuation was successful in 23 of 26 patients (88.5%) with superficial implantation and in 8 of 14 patients (57.1%) with deep implantation. Patients who failed primary surgical evacuation showed complete recovery, with uterus preservation, after salvage interventions, including laparoscopic surgery, angioembolization, and laparotomy. CONCLUSION(S): Preoperative determination of CSP implantation depth and extent is important in selecting candidates for surgical treatment. Primary single-step surgical evacuation was successful in most patients with superficial implantation, but patients should be informed of the possibility of salvage interventions before undergoing surgical evacuation. PMID- 25123638 TI - Preferences and needs regarding future contact with donation offspring among identity-release gamete donors: results from the Swedish Study on Gamete Donation. AB - OBJECTIVE: To investigate the attitudes and preferences regarding future contact with donation offspring among identity-release donors of oocytes or sperm. DESIGN: Longitudinal cohort study. SETTING: University-based fertility clinics in Sweden. PATIENT(S): A total of 210 women and men were questioned 5-8 years after their donation of oocytes or sperm. INTERVENTION(S): Questionnaires given to donors prior to their donation and 5-8 years after donation. MAIN OUTCOME MEASURE(S): Donors' attitudes and preferences regarding future contact with their donation offspring. RESULT(S): A majority of identity-release oocyte (65%) and sperm (70%) donors were positive toward being contacted by an offspring of mature age. More than half wanted to be notified by the clinic when an offspring requested information about them, but about a third were negative toward receiving this information. One in four reported a need for counseling regarding future contact with an offspring. CONCLUSION(S): Several years after donation, a majority of identity-release oocyte and sperm donors show positive attitudes toward future contact with their offspring. Donors appear to have different preferences for information and support regarding such contact. Fertility clinics and health-care services should provide counseling regarding contact with an offspring to the donors who express a need for this. PMID- 25123639 TI - Increased risk of pregnancy-induced hypertension and operative delivery after conception induced by in vitro fertilization/intracytoplasmic sperm injection in women aged 40 years and older. AB - OBJECTIVE: To clarify the association between preconception fertility status and obstetric outcomes in women aged 40 years and older. DESIGN: Retrospective study by reviewing medical records. SETTING: Tertiary perinatal center in a university hospital. PATIENT(S): 330 women aged 40 years and older who delivered a singleton from 2006 to 2010, and 450 women aged 30 to 34 years who delivered at the same facility as controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of pregnancy-induced hypertension, gestational diabetes mellitus, preterm birth, low birth weight, and mode of delivery assessed based on the mode of conception; spontaneous conception (SC) and in vitro fertilization/intracytoplasmic sperm injection conception (IVF-ICSI). RESULT(S): The incidence of pregnancy-induced hypertension was statistically significantly higher in IVF-ICSI group than the SC group. This gap was commonly observed in both the women aged 40 years and older and those in the 30 to 34 age group. No statistically significant difference was observed in the frequency of gestational diabetes mellitus, preterm birth, or low birth weight. As a characteristic of nulliparous women of advanced age, the rate of operative delivery, which includes emergency cesarean section and instrumental delivery, was statistically significantly higher in IVF-ICSI group than in the SC group. Detailed investigation into the medical indications for operative delivery revealed that the difference was attributable to the elevated incidence of labor protraction and arrest. CONCLUSION(S): Preconception fertility status can be a predicting factor of the incidence of pregnancy-induced hypertension and labor outcome, especially for women aged 40 years and older. PMID- 25123640 TI - Refined phenotyping, large cohorts, and collaborative research are vital for realizing the potential of genomics to transform care for male infertility. PMID- 25123641 TI - Resolvins RvD1 and 17(R)-RvD1 alleviate signs of inflammation in a rat model of endometriosis. AB - OBJECTIVE: To study the effects of two resolvins of D series, RvD1 and 17(R) RvD1, on inflammatory signs associated with endometriosis (ENDO). DESIGN: In vivo research study. SETTING: Research laboratory. ANIMAL(S): Female Sprague-Dawley rats. INTERVENTION(S): Intravenous or intraperitoneal injections of RvD1 (300 ng/kg) or 17(R)-RvD1 (300 and 900 ng/kg) in rats with surgically induced ENDO. MAIN OUTCOME MEASURE(S): Vascular permeability of ectopic endometrial growths was assessed by Evans Blue extravasation; vaginal hyperalgesia was assessed with telemetered visceromotor response. RESULT(S): Both resolvins, but not vehicle, significantly decreased vascular permeability in ectopic endometrial tissue. 17(R)-RvD1 also significantly alleviated severity of vaginal hyperalgesia. CONCLUSION(S): Our results suggest that RvD1 and 17(R)-RvD1 can be considered for further investigation of their therapeutic potential for treating ENDO. PMID- 25123643 TI - High-level expression in Escherichia coli, purification and kinetic characterization of Plasmodium falciparum M1-aminopeptidase. AB - Plasmodium falciparum neutral metallo-aminopeptidase (PfAM1), a member of the M1 family of metallo proteases, is a promising target for malaria, a devastating human parasitic disease. We report the high-level expression of PfAM1 in Escherichia coli BL21. An optimized gene, with a codon adaptation index and an average G/C content higher than the native gene, was synthesized and cloned in the pTrcHis2B vector. Optimal expression was achieved by induction with 1mM IPTG at 37 degrees C for 18h. This allowed obtaining 100mg of recombinant PfAM1 (rPfAM1) per L of culture medium; 19% of the E. coli soluble protein mass was from rPFAM1. rPfAM1, fused to an amino-terminal 6*His tag, was purified in a single step by immobilized metal ion affinity chromatography. The protein showed only limited signs of proteolytic degradation, and this step increased purity 27 fold. The kinetic characteristics of rPfAM1, such as a neutral optimal pH, a preference for substrates with basic or hydrophobic amino acids at the P1 position, an inhibition profile typical of metallo-aminopeptidases, and inhibition from Zn(2+) excess, were similar to those of the native PfAM1. We have thus optimized an expression system that should be useful for identifying new PfAM1 inhibitors. PMID- 25123644 TI - Seizure recurrence following pyridoxine withdrawal in a patient with pyridoxine dependent epilepsy. AB - Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive disorder characterized by early onset and recurrent seizures that can be controlled by a high dose of pyridoxine. PDE is caused by mutations in ALDH7A1, which encodes antiquitin. Antiquitin converts alpha-aminoadipic semialdehyde to alpha aminoadipic acid. Seizure recurrence after pyridoxine withdrawal is a criterion for diagnosis, but PDE can be diagnosed conclusively by genetic testing for mutations in the ALDH7A1 gene. In this case study, we report the long-term follow up of a patient suspected with PDE. She experienced prolonged generalized tonic seizures and was hospitalized in an intensive care unit following pyridoxine withdrawal. Later, we identified a compound heterozygous mutation, c.1216G>A, p.Gly406Arg, and a novel splice donor site mutation, IVS9+5G>A. Confirmation of these mutations would have prevented an unsafe withdrawal test. This case suggests the importance of the genetic determination of PDE to avoid the diagnostic withdrawal of pyridoxine. PMID- 25123642 TI - Efficient production and purification of recombinant human interleukin-12 (IL-12) overexpressed in mammalian cells without affinity tag. AB - Interleukin-12 is a heterodimeric, pro-inflammatory cytokine that is a key driver of cell-mediated immunity. Clinical interest in IL-12 is significant due to its potent anti-tumor activity and efficacy in controlling certain infectious diseases such as Leishmaniasis and Listeria infection. For clinical applications, the ease of production and purification of IL-12 and the associated cost continues to be a consideration. In this context, we report a simple and effective heparin-affinity based purification of recombinant human IL-12 (hIL-12) from the serum-free supernatants of stable IL-12-transduced HEK293 cells. Fractionation of culture supernatants on heparin Sepharose columns revealed that hIL-12 elutes as a single peak in 500 mM NaCl. Coomassie staining and Western blot analysis showed that hIL-12 eluted in 500 mM NaCl is homogeneous. Purity of hIL-12 was ascertained by RP-HPLC and ESI-MS analysis, and found to be ~98%. Western blot analysis, using monoclonal antibodies, demonstrated that the crucial inter-subunit disulfide bond linking the p35 and p40 subunits is intact in the purified hIL-12. Results of far UV circular dichroism, steady-state tryptophan fluorescence, and differential scanning calorimetry experiments suggest that purified hIL-12 is in its stable native conformation. Enzyme linked immunosorbent assays (ELISAs) and bioactivity studies demonstrate that hIL-12 is obtained in high yields (0.31+/-0.05 mg/mL of the culture medium) and is also fully bioactive. Isothermal titration calorimetry data show that IL-12 exhibits a moderate binding affinity (Kd(app)=69+/-1 MUM) to heparin. The purification method described in this study is expected to provide greater impetus for research on the role of heparin in the regulation of the function of IL-12. In addition, the results of this study provide an avenue to obtain high amounts of IL-12 required for structural studies which are aimed at the development of novel IL-12-based therapeutics. PMID- 25123645 TI - Chronic cannabinoid receptor stimulation selectively prevents motor impairments in a mouse model of Huntington's disease. AB - Huntington's disease (HD) is a devastating neurodegenerative disease characterized by a progressive decline in motor abilities, as well as in cognitive and social behaviors. Most of these behavioral deficits are recapitulated in the R6/1 transgenic mouse, which can therefore be used as an experimental model to identify the neurobiological substrates of HD pathology and to design novel therapeutic approaches. The endocannabinoid system (ECS) is a relevant candidate to participate in the etiopathology of HD as it is a key modulator of brain function, especially in areas primarily affected by HD dysfunction such as the striatum. Thus, some studies have demonstrated an association between HD progression and alterations in the expression of several ECS elements, thereby suggesting that improving ECS function may constitute a useful strategy to eliminate or at least delay the appearance of HD symptoms. Here this hypothesis was specifically tested by evaluating whether the administration of a well-characterized cannabinoid receptor agonist (WIN 55,212), either acutely or chronically, improves the HD-like symptoms in R6/1 mice. While acute treatment did not change the behavioral phenotype of transgenic animals, chronic administration was able to prevent the appearance of motor deficits, to increase the number of striatal huntingtin inclusions and to prevent the loss of striatal medium-sized spiny neurons, without affecting the social or cognitive alterations. These findings suggest that prolonged administration of cannabinoid receptor agonists could be an appropriate strategy for selectively improving motor symptoms and stimulating neuroprotective processes in HD patients. PMID- 25123646 TI - Inducing Muscle Heat Shock Protein 70 Improves Insulin Sensitivity and Muscular Performance in Aged Mice. AB - Heat shock proteins (HSPs) are molecular chaperones with roles in longevity and muscular preservation. We aimed to show elevating HSP70 improves indices of health span. Aged C57/BL6 mice acclimated to a western diet were randomized into: geranylgeranylacetone (GGA)-treated (100 mg/kg/d), biweekly heat therapy (HT), or control. The GGA and HT are well-known pharmacological and environmental inducers of HSP70, respectively. Assessments before and after 8 weeks of treatment included glycemic endpoints, body composition, and muscular endurance, power, and perfusion. An HT mice had more than threefold, and GGA mice had a twofold greater HSP70 compared with control. Despite comparable body compositions, both treatment groups had significantly better insulin sensitivity and insulin signaling capacity. Compared with baseline, HT mice ran 23% longer than at study start, which was significantly more than GGA or control. Hanging ability (muscular endurance) also tended to be best preserved in HT mice. Muscle power, contractile force, capillary perfusion, and innervation were not different. Heat treatment has a clear benefit on muscular endurance, whereas HT and GGA both improved insulin sensitivity. Different effects may relate to muscle HSP70 levels. An HSP induction could be a promising approach for improving health span in the aged mice. PMID- 25123648 TI - Delayed duodenal obstruction after intramural hematoma in a patient with paroxysmal nocturnal hemoglobinuria: A case report. AB - INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disorder of hematopoietic cells. Gastrointestinal complications of PNH are rare and mostly related with intravascular thrombosis or intramural hematoma. PRESENTATION OF CASE: We describe a case of a man with PNH complicated by intramural duodenal hematoma initially treated with supportive care. Three months after his first admission; he was admitted to the emergency department with abdominal pain, nausea and vomiting. He had undergone to surgery because of duodenal obstruction was treated with duodenojejunal by-pass surgery. DISCUSSION: Patients were healed from gastrointestinal complications could suffer from gastrointestinal strictures, which cause wide spread symptoms ranging from chronic abdominal pain and anorexia to intestinal obstruction. CONCLUSION: We report a rare intestinal obstruction case caused by stricture at the level of ligamentum Treitz with PNH. The possibility simply has to be borne in mind that strictures can be occurring at hematoma, ischemia or inflammation site of gastrointestinal tract. PMID- 25123649 TI - Malignant triton tumour of the sinonasal tract: Case report and literature review. AB - INTRODUCTION: The objective is to report a rare tumour of the sinonasal tract and conduct a literature review. Malignant triton tumour is a subtype of malignant schwannoma with rhabdomyoblastic differentiation. It is a very rare tumour, with only 15 reported cases involving the sinonasal region. PRESENTATION OF CASE: Forty-seven years old female presented with a right-sided epistaxis, progressive right sided nasal obstruction and anosmia and a visible mass in the right nasal cavity. Imaging studies showed a mass extending from the piriform aperture to the nasopharynx in contact with the dura and the orbital content. The mass was biopsied and the result was consistent with malignant triton tumour. The patient refused the surgery at first so chemotherapy with MAID protocol was started. After the fourth course of chemotherapy the treatment was stopped due to patient intolerance and a thrombosis of the jugular vein. Patient then underwent surgery with frontal craniotomy and dural excision, endoscopic control was done at the end to insure a complete removal. The patient received Radiotherapy in the postoperative period (56 Greys). At 5 years of follow up the patient is doing fine with no signs of recurrence and normal ophthalmological findings. DISCUSSION: Sixteen cases, including our case, have been reported to date in the literature. The mean age at presentation is 61 years. None of cases were associated with neurofibromatosis type 1. Eight patients were reported to be alive 5 years post-treatment, and 2 patients were reported to have died of the disease. The prognosis for triton tumours in the sinonasal tract is better than that for triton tumours in other locations. CONCLUSION: Malignant triton tumour is a rare malignancy of the sinonasal tract. Otolaryngologists should be aware of this disease. The optimal treatment should include radical resection of the tumour. PMID- 25123647 TI - Circulating Proteomic Signatures of Chronological Age. AB - To elucidate the proteomic features of aging in plasma, the subproteome targeted by the SOMAscan assay was profiled in blood samples from 202 females from the TwinsUK cohort. Findings were replicated in 677 independent individuals from the AddNeuroMed, Alzheimer's Research UK, and Dementia Case Registry cohorts. Results were further validated using RNAseq data from whole blood in TwinsUK and the most significant proteins were tested for association with aging-related phenotypes after adjustment for age. Eleven proteins were associated with chronological age and were replicated at protein level in an independent population. These were further investigated at gene expression level in 384 females from the TwinsUK cohort. The two most strongly associated proteins were chordin-like protein 1 (meta-analysis beta [SE] = 0.013 [0.001], p = 3.66 * 10(-46)) and pleiotrophin (0.012 [0.005], p = 3.88 * 10(-41)). Chordin-like protein 1 was also significantly correlated with birthweight (0.06 [0.02], p = 0.005) and with the individual Framingham 10-years cardiovascular risk scores in TwinsUK (0.71 [0.18], p = 9.9 * 10(-5)). Pleiotrophin is a secreted growth factor with a plethora of functions in multiple tissues and known to be a marker for cardiovascular risk and osteoporosis. Our study highlights the importance of proteomics to identify some molecular mechanisms involved in human health and aging. PMID- 25123650 TI - An electronic environment and contact direction sensitive scoring function for predicting affinities of protein-ligand complexes in Contour((r)). AB - Contour((r)) is a computational structure-based drug design technology that grows drug-like molecules by assembling context sensitive fragments in well-defined binding pockets. The grown molecules are scored by a novel empirical scoring function developed using high-resolution crystal structures of diverse classes of protein-ligand complexes and associated experimental binding affinities. An atomic model bearing features of the valence bond and VSEPR theories embodying their molecular electronic environment has been developed for non-covalent intermolecular interactions. On the basis of atomic hybridization and polarization states, each atom is modeled by features representing electron lone pairs, p-orbitals, and polar and non-polar hydrogens. A simple formal charge model was used to differentiate between polar and non-polar atoms. The interaction energy and the desolvation contribution of the protein-ligand association energy is computed as a linear sum of pair-wise interactions and desolvation terms. The pair-wise interaction energy captures short-range positive electrostatic interactions via hydrogen bonds, electrostatic repulsion of like charges, and non-bond contacts. The desolvation energy is estimated by calculating the energy required to desolvate interaction surfaces of the protein and the ligand in the complex. The scoring function predicts binding energies of a diverse set of protein-ligand complexes used for training with a correlation coefficient of 0.61. It also performs equally well in predicting association energies of a diverse validation set of protein-ligand complexes with a correlation coefficient of 0.57, which is equivalent to or better than 12 other scoring functions tested against this set including X-Score, GOLD, and DrugScore. PMID- 25123651 TI - Computational and statistical study on the molecular interaction between antigen and antibody. AB - Monoclonal antibodies are one of the most successful bio-molecules utilized in the clinical scene of today. It is important to clarify general characteristics of the interaction between antigen and antibody and to draw a guide for enhancing their binding affinity in rational design of antibody drugs. In this study, we carried out molecular dynamics simulations for 20 kinds of antigen-antibody complexes. From the statistical analysis of the calculation results, the following findings were deduced. At complementarity determining regions (CDRs) of the antibodies, the rates for the presence of serine (Ser) and tyrosine (Tyr) are high. The amino residues involved in direct hydrogen bonds between antigens and antibodies were examined by counting the numbers of the hydrogen bonds from the respective residues. The contribution of Tyr to the direct hydrogen bonding was the highest and that of Ser was the fourth. Furthermore, the short-distance hydrogen bonds, which is assumed to be so-called "low-barrier hydrogen bond", were observed at CDRs in three complexes. Interestingly, Ser is involved in the short-distance hydrogen bonding in two cases out of the three. This result suggests that these two unchanged polar amino acid residues play an important role for recognition of antigen. In almost all of the complexes (18/20), the contribution of the electrostatic energy (DeltaEele) to the binding free energy was calculated to be larger than that of the van der Waals energy (DeltaEvdw). This dominance of the electrostatic energy is in contrast to the case that low molecular-weight compounds are bound to their targets. The findings of this study will be helpful to design an antibody with a high specificity and a high affinity to the antigen. PMID- 25123652 TI - Distortion from planarity in arenes produced by internal rotation of one single hydroxyl hydrogen: the case of alternariol. AB - Alternariol (AOH) and alternariol methyl ether (AME) are compounds toxic to farm animals and humans produced by ubiquitous fungi of the Alternaria genus. Information on chemical and physical properties of these compounds is rather scarce although their X-ray structures are known. AOH and AME are composed of three aromatic rings with three hydroxyl groups. However, the crystal structure of AOH is nonplanar whereas that of AME which differs only in one methyl group substituting one hydroxyl hydrogen is planar. By means of quantum calculations we find that the internal rotation of that single hydrogen affects the structure of AOH producing deviations from planarity near 5 degrees . We also show that although quantum calculations predict energy differences about 5kcal/mol between planar and perpendicular conformations of that hydrogen, its rotation has no noticeable effects on electron density properties that could indicate modifications of aromaticity features. Based upon these results, we suggest an explanation to the nonplanarity of the AOH crystal solely in terms of the spatial arrangement of molecules in the crystal interconnected through a network of hydrogen bonds involving rotatable hydroxyl hydrogens that produce distortions from planarity. PMID- 25123653 TI - Evaluation of novel reactive MgO activated slag binder for the immobilisation of lead and zinc. AB - Although Portland cement is the most widely used binder in the stabilisation/solidification (S/S) processes, slag-based binders have gained significant attention recently due to their economic and environmental merits. In the present study, a novel binder, reactive MgO activated slag, is compared with hydrated lime activated slag in the immobilisation of lead and zinc. A series of lead or zinc-doped pastes and mortars were prepared with metal to binder ratio from 0.25% to 1%. The hydration products and microstructure were studied by X-ray diffraction, thermogravimetric analysis and scanning electron microscopy. The major hydration products were calcium silicate hydrate and hydrotalcite-like phases. The unconfined compressive strength was measured up to 160 d. Findings show that lead had a slight influence on the strength of MgO-slag paste while zinc reduced the strength significantly as its concentration increased. Leachate results using the TCLP tests revealed that the immobilisation degree was dependent on the pH and reactive MgO activated slag showed an increased pH buffering capacity, and thus improved the immobilisation efficiency compared to lime activated slag. It was proposed that zinc was mainly immobilised within the structure of the hydrotalcite-like phases or in the form of calcium zincate, while lead was primarily precipitated as the hydroxide. It is concluded, therefore, that reactive MgO activated slag can serve as clinker-free alternative binder in the S/S process. PMID- 25123654 TI - Adherence to diet and fluid restriction of individuals on hemodialysis treatment and affecting factors in Turkey. AB - AIM: This study was conducted to determine adherence to diet and fluid restriction in hemodialysis-treated individuals and the affecting factors in Turkey. METHODS: This descriptive study was conducted between 15 October 2010 and 15 January 2011 in subjects who voluntarily agreed to participate in the study from three dialysis centers in a city located in the Central Anatolia Region of Turkey. One hundred and twenty-one individuals treated with hemodialysis made up the study sample. The data were collected using a questionnaire consisting of 41 questions and the Dialysis Diet and Fluid Non-adherence Questionnaire. The data were evaluated with percentage, median, Mann-Whitney U-test, Kruskal-Wallis test, Student's t-test in independent samples and Spearman's rank correlation coefficient. RESULTS: The authors found that 98.3% of the individuals experienced non-adherence to diet and 95.0% with fluid restriction. The authors found a weak and negative relationship between calcium levels and non-adherence to fluid restriction, a weak relationship between phosphorus levels and diet non-adherence frequency and degree and the fluid non-adherence frequency scores, and a moderate positive relationship between phosphorus levels and fluid restriction non adherence degree scores (P < 0.05). CONCLUSION: Based on these results, regular training and information regarding diet and fluid restriction must be provided to individuals aged 21-35 years with no one in the family to help with their care, those who consumed salted food, or had interdialytic weight gain of 4.5 kg or more. PMID- 25123655 TI - Role of somatic cancer mutations in human protein lysine methyltransferases. AB - Methylation of lysine residues is an important post-translational modification of histone and non-histone proteins, which is introduced by protein lysine methyltransferases (PKMTs). An increasing number of reports demonstrate that aberrant lysine methylation plays a central role in carcinogenesis that is often correlated with abnormal expression of PKMTs. Recent whole genome and whole transcriptome sequencing projects have also discovered several somatic mutations in PKMTs that frequently appear in various tumors. These include chromosomal translocations that lead to aberrant expression or mistargeting of PKMTs and nonsense or frameshift mutations, which cause the loss of the protein function. Another type of mutations are missense mutations which may lead to the loss of enzyme activity, but may also alter the properties of PKMTs either by changing the product or substrate specificity or by increasing the enzymatic activity finally leading to a gain-of-function phenotype. In this review, we provide an overview of the roles of EZH2, SETD2, NSD family, SMYD family, MLL family and DOT1L PKMTs in cancer focusing on the effects of somatic cancer mutations in these enzymes. Investigation of the effect of somatic cancer mutations in PKMTs is pivotal to understand the general role of this important class of enzymes in carcinogenesis and to improve and develop more individualized cancer therapies. PMID- 25123656 TI - A validated score estimating ambulatory status following radiotherapy of elderly patients for metastatic spinal cord compression. AB - BACKGROUND: This study was performed to develop a validated score predicting ambulatory status after radiotherapy (RT) alone for metastatic spinal cord compression (MSCC) in elderly patients. METHODS: 1,129 elderly patients (>=65 years) were assigned to the test (N = 565) or validation group (N = 564). In the test group, nine pre-treatment factors (age, gender, tumor type, number of involved vertebrae, pre-RT ambulatory status, other bone metastases, visceral metastases, interval cancer diagnosis to RT, time developing motor deficits) and fractionation regimen were investigated. Factors significantly associated with post-RT ambulatory status on multivariate analysis were included in the score. The score for each factor was determined by dividing the post-RT ambulatory rate at 1 month (%) by 10. The total score represented the sum of these scores. RESULTS: In the multivariate analysis of the test group, age, primary tumor type, pre-RT ambulatory status, visceral metastases, and time developing motor deficits were significantly associated with post-RT ambulatory status. Total scores were 19 to 41 points. In the test group, post-RT ambulatory rates were 5% for 19-25 points, 35% for 26-30 points, 80% for 31-34 points, and 98% for 35-41 points (p < 0.001). 6-month survival rates were 11%, 21%, 59% and 76%, respectively. In the validation group, post-RT ambulatory rates were 4%, 33%, 77% and 98%, respectively (p < 0.001). CONCLUSIONS: Patients achieving 19-25 points had very poor functional outcomes and survival, and may receive single-fraction RT for pain relief. Selected patients with 26-34 points may benefit from additional surgery. Patients achieving >=35 points achieved favorable results after RT alone. PMID- 25123658 TI - Randomness in highly reflective silver nanoparticles and their localized optical fields. AB - Reflection of near-infrared light is important for preventing heat transfer in energy saving applications. A large-area, mass-producible reflector that contains randomly distributed disk-shaped silver nanoparticles and that exhibits high reflection at near-infrared wavelengths was demonstrated. Although resonant coupling between incident light and the nanostructure of the reflector plays some role, what is more important is the geometrical randomness of the nanoparticles, which serves as the origin of a particle-dependent localization and hierarchical distribution of optical near-fields in the vicinity of the nanostructure. Here we show and clarified the unique optical near-field processes associated with the randomness seen in experimentally fabricated silver nanostructures by adapting a rigorous theory of optical near-fields based on an angular spectrum and detailed electromagnetic calculations. PMID- 25123657 TI - The role of ClpP, RpoS and CsrA in growth and filament formation of Salmonella enterica serovar Typhimurium at low temperature. AB - BACKGROUND: Salmonellae are food-borne pathogens of great health and economic importance. To pose a threat to humans, Salmonellae normally have to cope with a series of stressful conditions in the food chain, including low temperature. In the current study, we evaluated the importance of the Clp proteolytic complex and the carbon starvation protein, CsrA, for the ability of Salmonella Typhimurium to grow at low temperature. RESULTS: A clpP mutant was severely affected in growth and formed pin point colonies at 10 degrees C. Contrary to this, rpoS and clpP/rpoS mutants were only slightly affected. The clpP mutant formed cold resistant suppressor mutants at a frequency of 2.5 * 10(-3) and these were found not to express RpoS. Together these results indicated that the impaired growth of the clpP mutant was caused by high level of RpoS. Evaluation by microscopy of the clpP mutant revealed that it formed filamentous cells when grown at 10 degrees C, and this phenotype too, disappered when rpoS was mutated in parallel indicating a RpoS-dependency. A csrA (sup) mutant was also growth attenuated a low temperature. An rpoS/csrA (sup) double mutant was also growth attenuated, indicating that the phenotype of the csrA mutant was independent from RpoS. CONCLUSIONS: The cold sensitivity of clpP mutant was associated with increased levels of RpoS and probably caused by toxic levels of RpoS. Although a csrA mutant also accumulated high level of RpoS, growth impairment caused by lack of csrA was not related to RpoS levels in a similar way. PMID- 25123659 TI - A comprehensive survey of non-canonical splice sites in the human transcriptome. AB - We uncovered the diversity of non-canonical splice sites at the human transcriptome using deep transcriptome profiling. We mapped a total of 3.7 billion human RNA-seq reads and developed a set of stringent filters to avoid false non-canonical splice site detections. We identified 184 splice sites with non-canonical dinucleotides and U2/U12-like consensus sequences. We selected 10 of the herein identified U2/U12-like non-canonical splice site events and successfully validated 9 of them via reverse transcriptase-polymerase chain reaction and Sanger sequencing. Analyses of the 184 U2/U12-like non-canonical splice sites indicate that 51% of them are not annotated in GENCODE. In addition, 28% of them are conserved in mouse and 76% are involved in alternative splicing events, some of them with tissue-specific alternative splicing patterns. Interestingly, our analysis identified some U2/U12-like non-canonical splice sites that are converted into canonical splice sites by RNA A-to-I editing. Moreover, the U2/U12-like non-canonical splice sites have a differential distribution of splicing regulatory sequences, which may contribute to their recognition and regulation. Our analysis provides a high-confidence group of U2/U12-like non-canonical splice sites, which exhibit distinctive features among the total human splice sites. PMID- 25123660 TI - DEAD-box RNA helicase domains exhibit a continuum between complete functional independence and high thermodynamic coupling in nucleotide and RNA duplex recognition. AB - DEAD-box helicases catalyze the non-processive unwinding of double-stranded RNA (dsRNA) at the expense of adenosine triphosphate (ATP) hydrolysis. Nucleotide and RNA binding and unwinding are mediated by the RecA domains of the helicase core, but their cooperation in these processes remains poorly understood. We therefore investigated dsRNA and nucleotide binding by the helicase cores and the isolated N- and C-terminal RecA domains (RecA_N, RecA_C) of the DEAD-box proteins Hera and YxiN by steady-state and time-resolved fluorescence methods. Both helicases bind nucleotides predominantly via RecA_N, in agreement with previous studies on Mss116, and with a universal, modular function of RecA_N in nucleotide recognition. In contrast, dsRNA recognition is different: Hera interacts with dsRNA in the absence of nucleotide, involving both RecA domains, whereas for YxiN neither RecA_N nor RecA_C binds dsRNA, and the complete core only interacts with dsRNA after nucleotide has been bound. DEAD-box proteins thus cover a continuum from complete functional independence of their domains, exemplified by Mss116, to various degrees of inter-domain cooperation in dsRNA binding. The different degrees of domain communication and of thermodynamic linkage between dsRNA and nucleotide binding have important implications on the mechanism of dsRNA unwinding, and may help direct RNA helicases to their respective cellular processes. PMID- 25123661 TI - A high security double lock and key mechanism in HUH relaxases controls oriT processing for plasmid conjugation. AB - Relaxases act as DNA selection sieves in conjugative plasmid transfer. Most plasmid relaxases belong to the HUH endonuclease family. TrwC, the relaxase of plasmid R388, is the prototype of the HUH relaxase family, which also includes TraI of plasmid F. In this article we demonstrate that TrwC processes its target nic-site by means of a highly secure double lock and key mechanism. It is controlled both by TrwC-DNA intermolecular interactions and by intramolecular DNA interactions between several nic nucleotides. The sequence specificity map of the interaction between TrwC and DNA was determined by systematic mutagenesis using degenerate oligonucleotide libraries. The specificity map reveals the minimal nic sequence requirements for R388-based conjugation. Some nic-site sequence variants were still able to form the U-turn shape at the nic-site necessary for TrwC processing, as observed by X-ray crystallography. Moreover, purified TrwC relaxase effectively cleaved ssDNA as well as dsDNA substrates containing these mutant sequences. Since TrwC is able to catalyze DNA integration in a nic-site containing DNA molecule, characterization of nic-site functionally active sequence variants should improve the search quality of potential target sequences for relaxase-mediated integration in any target genome. PMID- 25123662 TI - Effects of supercoiling on enhancer-promoter contacts. AB - Using Brownian dynamics simulations, we investigate here one of possible roles of supercoiling within topological domains constituting interphase chromosomes of higher eukaryotes. We analysed how supercoiling affects the interaction between enhancers and promoters that are located in the same or in neighbouring topological domains. We show here that enhancer-promoter affinity and supercoiling act synergistically in increasing the fraction of time during which enhancer and promoter stay in contact. This stabilizing effect of supercoiling only acts on enhancers and promoters located in the same topological domain. We propose that the primary role of recently observed supercoiling of topological domains in interphase chromosomes of higher eukaryotes is to assure that enhancers contact almost exclusively their cognate promoters located in the same topological domain and avoid contacts with very similar promoters but located in neighbouring topological domains. PMID- 25123663 TI - Why double-stranded RNA resists condensation. AB - The addition of small amounts of multivalent cations to solutions containing double-stranded DNA leads to inter-DNA attraction and eventual condensation. Surprisingly, the condensation is suppressed in double-stranded RNA, which carries the same negative charge as DNA, but assumes a different double helical form. Here, we combine experiment and atomistic simulations to propose a mechanism that explains the variations in condensation of short (25 base-pairs) nucleic acid (NA) duplexes, from B-like form of homopolymeric DNA, to mixed sequence DNA, to DNA:RNA hybrid, to A-like RNA. Circular dichroism measurements suggest that duplex helical geometry is not the fundamental property that ultimately determines the observed differences in condensation. Instead, these differences are governed by the spatial variation of cobalt hexammine (CoHex) binding to NA. There are two major NA-CoHex binding modes--internal and external- distinguished by the proximity of bound CoHex to the helical axis. We find a significant difference, up to 5-fold, in the fraction of ions bound to the external surfaces of the different NA constructs studied. NA condensation propensity is determined by the fraction of CoHex ions in the external binding mode. PMID- 25123664 TI - Structural basis of lariat RNA recognition by the intron debranching enzyme Dbr1. AB - The enzymatic processing of cellular RNA molecules requires selective recognition of unique chemical and topological features. The unusual 2',5'-phosphodiester linkages in RNA lariats produced by the spliceosome must be hydrolyzed by the intron debranching enzyme (Dbr1) before they can be metabolized or processed into essential cellular factors, such as snoRNA and miRNA. Dbr1 is also involved in the propagation of retrotransposons and retroviruses, although the precise role played by the enzyme in these processes is poorly understood. Here, we report the first structures of Dbr1 alone and in complex with several synthetic RNA compounds that mimic the branchpoint in lariat RNA. The structures, together with functional data on Dbr1 variants, reveal the molecular basis for 2',5' phosphodiester recognition and explain why the enzyme lacks activity toward 3',5' phosphodiester linkages. The findings illuminate structure/function relationships in a unique enzyme that is central to eukaryotic RNA metabolism and set the stage for the rational design of inhibitors that may represent novel therapeutic agents to treat retroviral infections and neurodegenerative disease. PMID- 25123665 TI - 7SL RNA represses p53 translation by competing with HuR. AB - Noncoding RNAs (ncRNAs) and RNA-binding proteins are potent post-transcriptional regulators of gene expression. The ncRNA 7SL is upregulated in cancer cells, but its impact upon the phenotype of cancer cells is unknown. Here, we present evidence that 7SL forms a partial hybrid with the 3'-untranslated region (UTR) of TP53 mRNA, which encodes the tumor suppressor p53. The interaction of 7SL with TP53 mRNA reduced p53 translation, as determined by analyzing p53 expression levels, nascent p53 translation and TP53 mRNA association with polysomes. Silencing 7SL led to increased binding of HuR to TP53 mRNA, an interaction that led to the promotion of p53 translation and increased p53 abundance. We propose that the competition between 7SL and HuR for binding to TP53 3'UTR contributes to determining the magnitude of p53 translation, in turn affecting p53 levels and the growth-suppressive function of p53. Our findings suggest that targeting 7SL may be effective in the treatment of cancers with reduced p53 levels. PMID- 25123670 TI - The shell game: how institutional review boards shuffle words. AB - Concepts like coercion, vulnerability, and dignitary harm have acquired specialized meanings in the research ethics literature. Institutional Review Boards (IRBs), also called Research Ethics Committees (RECs), sometimes use these concepts in two different ways without acknowledging or even realizing what they are doing. IRBs mislabel any language that encourages subject participation in trials as "coercive," then demand its removal as if it were actually coercive in the sense of a threat of force. An example of language that is treated as coercive is the use of the word "hope" in an educational brochure about clinical trials. The concepts of vulnerability and dignitary harm are similarly misused. The regulations instruct IRBs to protect vulnerable groups; but IRBs sometimes use a group's vulnerability to one threat to protect it against an unrelated and harmless threat, as when homeless people, who are vulnerable to street crime and disease, are protected from the risk of an interview. Finally, the term "dignitary harm" is so vague that IRBs can use it to restrict research that is entirely free of risk, while ignoring the possibility that research might provide the dignitary benefit of contributing to society's health and welfare. Dignitary harm--usually nonphysical "harm" of which the subject is entirely unaware--can be deemed more important than obtaining information that subjects want or actual risk of physical injury. These vague or shifting definitions permit the IRB to play a shell game without either the board or the investigator realizing what is happening. PMID- 25123671 TI - Anatomy of a transformation: a systematic effort to reduce mechanical restraints at a state psychiatric hospital. AB - OBJECTIVE: The authors describe efforts to reduce use of mechanical restraints at a state psychiatric hospital. METHODS: Data were collected for individuals admitted to the acute adult unit (AAU) (N=2,910) and the community transition unit (CTU) (N=334) over three years. Two strategies aimed to reduce mechanical restraint use. First, staff were trained in deescalation techniques, and a response team was formed for crisis situations. Second, a policy change required prior approval for use of mechanical restraint. RESULTS: Mechanical restraint was significantly reduced on both units after the first strategy. After the second, additional reduction was noted on AAU (98% total reduction) but not on CTU, where the practice had already been eliminated. No increase in assaults or injuries was noted. CONCLUSIONS: Reduction in mechanical restraint use is possible through deescalation skills training, use of a response team, and policy changes. Strong leadership, staff buy-in, provision of feedback, and quality monitoring were also instrumental. PMID- 25123669 TI - Bicarbonate transport inhibitor SITS modulates pH homeostasis triggering apoptosis of Dalton's lymphoma: implication of novel molecular mechanisms. AB - Bicarbonate transporter (BCT) plays a crucial role in maintaining pH homeostasis of tumor cells by import of HCO3(-). This helps the tumor cells in manifesting extracellular tumor acidosis, accompanied by a relative intracellular alkalinization, which in turn promotes tumor progression. Therefore, blocking BCT mediated HCO3(-) transport is envisaged as a promising anticancer therapeutic approach. Thus, using a murine model of a T cell lymphoma, designated as Dalton's lymphoma (DL), in the present in vitro investigation the antitumor consequences of blocking BCT function by its inhibitor 4-acetamido-4-isothiocyanostilbene-2,2 disulfonate (SITS) were explored. Treatment of DL cells with SITS resulted in an increase in the extracellular pH, associated with a decline in DL cell survival and augmented induction of apoptosis. BCT inhibition also elevated the expression of cytochrome c, caspase-9, caspase-3, Bax, reactive oxygen species, and nitric oxide along with inhibition of HSP-70 and Bcl2, which regulate tumor cell survival and apoptosis. SITS-treated DL cells displayed upregulated production of IFN-gamma and IL-6 along with a decline of IL-10. Treatment of DL cells with SITS also inhibited the expression of fatty acid synthase, which is crucial for membrane biogenesis in neoplastic cells. The expression of lactate transporter MCT-1 and multidrug resistance regulating protein MRP-1 got inhibited along with hampered uptake of glucose and lactate production in SITS-treated DL cells. Thus, the declined tumor cell survival following inhibition of BCT could be the consequence of interplay of several inter-connected regulatory molecular events. The outcome of this study indicates the potential of BCT inhibition as a novel therapeutic approach for treatment of hematological malignancies. PMID- 25123673 TI - Similar radiopathological features, but different postoperative recurrence rates, between Stage I lung cancers arising in emphysematous lungs and those arising in nonemphysematous lungs. AB - OBJECTIVES: The aim of the present study was to clarify the differences between lung cancer arising in emphysematous lungs and that arising in nonemphysematous lungs with regard to radiopathological features and the postoperative recurrence rate. METHODS: We retrospectively reviewed a prospective database of 212 patients who underwent major lung resection for clinically diagnosed Stage I primary lung cancer. Emphysematous lungs were identified on the basis of quantitative computed tomography (CT). The biological features of the primary tumour were diagnosed according to the presence or absence of a ground-glass component on high resolution CT and the maximum standardized uptake value in [(18)F] fluorodeoxyglucose positron emission tomography, in addition to conventional characteristic factors. RESULTS: The risk factors for postoperative recurrence were underlying emphysema, a high maximum standardized uptake value, the absence of a ground-glass component, the pathological grade and lymph node metastasis, whereas the risk factors for lymph node metastasis were a high maximum standardized uptake value, the absence of a ground-glass component and the pathological grade. Surprisingly, these risk factors were entirely matched between patients with and without emphysematous lungs, regardless of the fact that patients with emphysematous lungs had a higher recurrence rate. CONCLUSIONS: Similar clinicopathological features, but different postoperative recurrence rates, were found between Stage I lung cancers arising in emphysematous lungs and those arising in nonemphysematous lungs. It may be valuable to search for underlying molecular mechanisms that promote metastasis from primary tumours arising in emphysema, such as paracrine effects between the tumour and pulmonary emphysema. PMID- 25123672 TI - Unilateral pulmonary oedema after minimally invasive cardiac surgery via right anterolateral minithoracotomy. AB - OBJECTIVES: To investigate the incidence of unilateral pulmonary oedema after minimally invasive cardiac surgery (MICS) requiring unilateral lung collapse has been unknown until now. METHODS: We analysed the data of 484 consecutive patients undergoing minimally invasive cardiac surgery with unilateral lung collapse between January 2008 and December 2013. The clinical regimen was changed in 2010 to a single dose of dexamethasone (approximately 1 mg/kg body weight) administered after anaesthesia induction. RESULTS: Thirty-eight patients developed a radiographically evident unilateral pulmonary oedema within 24 h after surgery. Dexamethasone significantly reduced the incidence of this event [4.0 vs 12.9%; unadjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.14 0.58, P < 0.001]. One patient with and six patients without dexamethasone were clinically symptomatic (P = 0.001). Logistic regression analysis identified four variables significantly associated with the development of a unilateral lung oedema: dexamethasone (OR 0.28, 95% CI 0.13-0.58, P = 0.001), diabetes mellitus (OR 3.17, 95% CI 1.04-9.63, P = 0.04), the level of mean pulmonary arterial pressure (OR 1.05 per mmHg, 95% CI 1.004-1.09, P = 0.03) and transfusion of fresh frozen plasma (OR 2.31, 95% CI 1.02-5.25, P = 0.045). CONCLUSIONS: Our data revealed a 7.9% incidence of radiographically evident unilateral pulmonary oedema after MICS with intraoperative collapse of a lung. Of the total number of patients, 1.5% simultaneously developed clinical symptoms. The influence of corticosteroids, as well as the contribution of possible risk factors, needs further evaluation. PMID- 25123674 TI - Comparison of the early haemodynamics of stented pericardial and porcine aortic valves. AB - Data comparing the haemodynamic performance of stented pericardial and porcine aortic valves are conflicting. Hence, we performed a systematic review and meta analysis comparing the early haemodynamic parameters of stented pericardial and porcine valves in patients undergoing isolated aortic valve replacement. Medline, EMBASE and Web of Science were queried for English language original publications from 2000 to 2013. Studies comparing porcine (PoV) and pericardial (PeV) with regard to their haemodynamic parameters were included in this review. Continuous data were pooled using the mean difference (MD) or the standardized mean difference (SMD). A random-effect inverse weighted analysis was conducted; a P value<0.05 is considered statistically significant. Results are presented with 95% confidence intervals. Thirteen studies (1265 PeV patients and 871 PoV patients) were included in this analysis. The pooled transvalvular mean gradient was lower for PeV [MD -4.6 (-6.45 to -2.77) mmHg; P<0.01]. Limiting this analysis to small valves (19 and 21 mm; eight studies; 714 patients) revealed that the PeV gradients were significantly lower [MD -4.5 (-5.7 to -3.2); P=0.001]. The corresponding effective orifice area of PeV was significantly larger than PoV [SMD 0.42 (0.15-0.69); P<0.01]. A sensitivity analysis comprising only randomized controlled trials did not significantly alter results. When compared with porcine valves, stented pericardial aortic valves have lower mean transvalvular gradients early after implant. Even pericardial valves in smaller sizes (19 and 21 mm) have a better haemodynamic profile when compared with their counterparts. PMID- 25123675 TI - Muscle metabolism during tibial lengthening with regular and high distraction rates. AB - INTRODUCTION: Muscle regeneration is promoted when the Ilizarov method is used for limb lengthening and deformity correction, but the regenerative ability of muscles decreases when achieving large amounts of elongation. Much research has been dedicated to studying the capabilities of muscles under lengthening, but no reports are available that investigate the muscle metabolism. We supposed that energy turnover would be activated in skeletal muscles under lengthening as a response to distraction, and the activity of the energy turnover would grow in proportion to the increase in the distraction rate or amount. MATERIALS AND METHODS: We compared the metabolism of canine anterior tibial muscles (ATMs) by regular and 3-mm high-frequency bone distraction in 30 dogs to obtain 14.5 +/- 0.8% lengthening from the initial tibial length. Group 1 (n = 12) had manual lengthening with a rate of 1 mm per day. Three millimeters per day was produced with 120 increments in automated mode in group 2 (n = 12). An intact group (n = 6) served as controls. ATMs were harvested at the end of distraction, after 30 days of fixation, and 30 days after frame removal. We assessed the activity of lactate dehydrogenase, creatine phosphokinase, glucoso-6-phosphate dehydrogenase, and catalase and calculated the concentration of malone dialdehyde, sarcoplasmic and contractile proteins in the ATM extract. RESULTS: Energy turnover reactions were activated in the ATM as a response to distraction forces, but the activity of the energy turnover did not grow proportionally to the increased distraction rate. Levels of sarcoplasmic and contractile proteins in the ATM decreased insignificantly in both groups. CONCLUSIONS: High-frequency 3-mm daily lengthening results in compensatory energy turnover changes in the muscle, sufficient for prevention of catabolic processes. PMID- 25123676 TI - Population-based study of the relationship between medial meniscus radial displacement, determined by use of ultrasound screening, and knee pain. AB - PURPOSE: The purpose of this population-based study was to clarify the incidence of knee pain by use of ultrasound (US). METHODS: Medical check-ups were conducted for residents of a mountain village in Japan. The subjects were 149 males and 252 females (802 knees) with a mean age of 63.5 +/- 12.5 years. US was used to evaluate the medial joint space of both knees, with and without weight-bearing. For each patient, medial radial displacement of the medial meniscus (MRD) and number of osteophytes were evaluated. A questionnaire was used to determine whether the subjects were currently experiencing knee pain while walking, climbing stairs, or resting that had lasted more than one month. A visual analog scale was used to assess knee pain. The subjects were divided into two groups, those with knee pain (P group) and those without knee pain (non-P group), on the basis of whether a visual analog scale (VAS) was less than or more than 20 mm during walking, climbing stairs, or resting. Logistic regression analysis was used to identify the factors associated with knee pain. RESULTS: Significantly different weight-bearing MRD (WMRD), osteophytes, and pain while walking, climbing stairs, or resting (p < 0.01) were found between the two groups. Logistic regression analysis showed that WMRD was significantly associated with knee pain during walking or while climbing stairs. CONCLUSION: We found that WMRD was significantly associated with knee pain while walking or climbing stairs, which are weight-bearing activities. On the basis of the findings of this study, we believe US is a useful tool for evaluating the factors associated with knee pain in a population-based study. LEVEL OF EVIDENCE: Level III. PMID- 25123677 TI - [Exophthalmus with enlarged epibulbar vessels]. PMID- 25123678 TI - Prebiotic potential of Jerusalem artichoke (Helianthus tuberosus L.) in Wistar rats: effects of levels of supplementation on hindgut fermentation, intestinal morphology, blood metabolites and immune response. AB - BACKGROUND: Many studies have been conducted using purified prebiotics such as inulin or fructooligosaccharides (FOS) as nutraceuticals, but there is very little information available on the prebiotic potential of raw products rich in inulin and FOS, such as Jerusalem artichoke (JA; Helianthus tuberosus L.). The present experiment aimed to evaluate the prebiotic effects of JA tubers in rats. RESULTS: Seventy-two Wistar weanling rats divided into four groups were fed for 12 weeks on a basal diet fortified with pulverized JA tubers at 0 (control), 20, 40 and 60 g kg(-1) levels. Enhanced cell-mediated immunity in terms of skin indurations (P = 0.082) and CD4+ T-lymphocyte population (P = 0.002) was observed in the JA-supplemented groups compared with the control group. Blood haemoglobin (P = 0.017), glucose (P = 0.001), urea (P = 0.004) and calcium (P = 0.048) varied favourably upon inclusion of JA. An increasing trend (P = 0.059) in the length of large intestine was apparent in the JA-fed groups. The tissue mass of caecum (P = 0.069) and colon (P = 0.003) was increased in the JA-supplemented groups, accompanied by higher (P = 0.007) caecal crypt depth. The pH and ammonia concentrations of intestinal digesta decreased and those of lactate and total volatile fatty acids increased in the JA-fed groups. CONCLUSION: The results suggest that JA had beneficial effects on immunity, blood metabolites, intestinal morphometry and hindgut fermentation of rats. PMID- 25123679 TI - Liquid biopsy in gastrointestinal stromal tumors: a novel approach. AB - The role of molecular analysis in the management of gastrointestinal stromal tumors (GIST) remains indisputable. To date, tumor tissue extracted from specimens obtained by surgical or biopsy procedures has been the only source of the tumor DNA required for the molecular and genomic assessment of cancer. However, tumor tissue sampling has several clinical limitations: for example, the invasiveness of these procedures precludes repeated sampling. Thus, it is possible to obtain only a static molecular picture of the disease, a picture that lacks the inter- and intra-metastatic molecular heterogeneity that characterizes most GIST. In contrast, circulating tumor DNA obtained from a patient's bloodstream, known as liquid biopsy, can theoretically overcome the limitations of tissue biopsies and provide the same molecular and genomic information. GIST are recognized as a paradigm of molecular biology among solid tumors. Although few but promising data on liquid biopsy in GIST have been accumulated to date, these tumors may provide the optimal field for application of this challenging approach. PMID- 25123681 TI - Epidemiological characteristics and immune status of children with Respiratory Syncytial Virus. AB - Respiratory Syncytial Virus (RSV) infections are the dominant cause of pneumonia in children. In order to determine the epidemiological characteristics and immune status of children with Respiratory Syncytial Virus, a prospective study was performed among patients with RSV infection. Comparisons between RSV pneumonia group and normal control group, RSV pneumonia group had lower IL-2 (median levels, pg/ml: 3.8 vs. 5.1, P < 0.01), and higher IL-4 (median levels, pg/ml: 3.2 vs. 2.4, P < 0.01), IL-10 (median levels, pg/ml: 12.2 vs. 2.3, P < 0.01), and IFN gamma (median levels, pg/ml: 13.4 vs. 4.6, P < 0.01). The level of IgE among pneumonia patients caused by RSV increased sharply (median levels, mg/L: 48.1 vs. 8.8, P < 0.01). Another amazing finding is that after birth, the degree of IgE of the children infected by RSV increases gradually with age. This effect is at its peak in 0.6 years old. The IgE and eosinophil levels were higher when patients suffered from RSV pneumonia with wheeze (IgE median levels, IU/ml: with wheeze: 72.74 vs. without wheeze: 11.5, P < 0.05; eosinophil median levels, *10(9) /l: with wheeze: 0.21 vs. without wheeze: 0.05, P < 0.05). The main morbidity crowd is the children under the age of 1 year old. The downregulation of IL2 and the upregulation of IL-4, IL-10, IFN-gamma, and IgE happen after RSV infection. PMID- 25123680 TI - The prevalence of general and abdominal obesity according to sasang constitution in Korea. AB - BACKGROUND: Obesity is an important risk factor for cardiovascular and metabolic diseases and could affect mortality rates. Body mass index (BMI) and waist circumference (WC) have been used to classify obesity, and waist-to-hip ratio (WHR) has recently emerged as a discriminator of cardiovascular disease. Sasang constitution (SC) is a kind of well-known traditional Korean medicine: Tae-eumin (TE), Soeumin (SE), Taeyangin (TY) and Soyangin (SY) carrying a different level of susceptibility to chronic diseases. We aimed to examine the prevalence in general and abdominal obesity (AO) using BMI, WC and WHR according to SC in the Korean population. METHODS: A total of 3,348 subjects were recruited from 24 Korean medicine clinics. Obesity was divided into three categories: general obesity by BMI, abdominal obesity by waist circumference (WC AO) and abdominal obesity by waist-to-hip ratio (WHR AO). A Chi-square test was performed to compare prevalence, and logistic regression was conducted to generate odds ratios (ORs) according to SC (p < .05). RESULTS: The prevalence of general obesity was significantly higher in males than in females. The highest prevalence of general obesity, WC AO and WHR AO were all observed in the TE type, and the SY and SE types were followed in order, for both males and females respectively.The TE type was highly associated with increased risk of general obesity (OR = 20.2, 95% CI: 12.4-32.9 in males and OR = 14.3, 95% CI: 10.1-20.2 in females), of WC AO (OR = 10.7, 95% CI: 7.2-15.9 in males and OR = 7.5, 95% CI: 5.8-9.6 in females), and of WHR AO (OR = 4.6, 95% CI: 3.3-6.4 in males and OR = 3.8, 95% CI: 2.9-4.9 in females) compared with the SE type. In addition, after controlling for age, social status and eating habits, the ORs were similar to the crude model according to gender and SC. CONCLUSIONS: This study shows that the prevalence of obesity varies according to SC in the Korean population. In particular, the TE type was highly associated with increased ORs for general obesity, WC AO and WHR AO in both genders. PMID- 25123682 TI - Influence of body mass index on skin grafting in pediatric burns. AB - BACKGROUND: There is heterogeneous literature on the association of obese and underweight body habitus on burn outcomes in adult and pediatric literature. We examine the effect of standardized pediatric body mass index (BMI) categories skin graft utilisation. METHODS: A retrospective chart review was performed on children who underwent burn treatment from January 1995 to November 2011. BMI was categorized by standard definitions: underweight (<5%), normal (5-85%), overweight (85-95%), obese (>95%). RESULTS: There were 1164 patients: 77 underweight, 604 normal, 215 overweight, and 268 obese patients. No differences existed between group demographics. Grafts were performed in 39% of underweight, 27% of normal, 22% of overweight, and 27% of obese patients. Underweight children had nearly a 2 fold increase in their risk of full thickness burns and were 1.8 times more likely to undergo skin grafting than normal BMI children. Overweight children had a significant decrease in the incidence skin grafting by 23% then compared to normal weight children. There were no differences in percent TBSA burned or percent TBSA grafted using ANOVA. CONCLUSIONS: Underweight pediatric burn victims have an increased risk for skin grafting while mildly overweight children are slightly protected from skin grafting. PMID- 25123683 TI - Antigenic properties of N protein of hantavirus. AB - Hantavirus causes two important rodent-borne viral zoonoses, hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in North and South America. Twenty-four species that represent sero- and genotypes have been registered within the genus Hantavirus by the International Committee on Taxonomy of Viruses (ICTV). Among the viral proteins, nucleocapsid (N) protein possesses an immunodominant antigen. The antigenicitiy of N protein is conserved compared with that of envelope glycoproteins. Therefore, N protein has been used for serological diagnoses and seroepidemiological studies. An understanding of the antigenic properties of N protein is important for the interpretation of results from serological tests using N antigen. N protein consists of about 430 amino acids and possesses various epitopes. The N-terminal quarter of N protein bears linear and immunodominant epitopes. However, a serotype-specific and multimerization-dependent antigenic site was found in the C-terminal half of N protein. In this paper, the structure, function, and antigenicity of N protein are reviewed. PMID- 25123685 TI - Training endosonographers in cytopathology: improving the results of EUS-guided FNA. AB - BACKGROUND: Although on-site cytopathology services have a significant impact on efficiency and accuracy of EUS-guided FNA (EUS-FNA), the availability of this service is variable. OBJECTIVE: To evaluate the impact of an intensive 2-day training program to educate endosonographers in EUS-related cytopathology. DESIGN: Pilot study. SETTING: Tertiary care medical center. SUBJECTS: Six endosonographers (5 male, median age, 35 years) with minimal previous cytopathology exposure comprised the study cohort. METHODS: Pre- and posttraining testing was administered. Training commenced with a cytopathology tutorial focusing on 4 performance measures: specimen adequacy, sample interpretation, specimen processing, and preliminary diagnosis. Eight live EUS-FNA cases were then performed, and study participants independently completed 4 questions based on performance measures for each case. The ability to independently smear and stain slides and operate a microscope was additionally assessed after a hands-on tutorial. MAIN OUTCOME MEASUREMENTS: Comparison of pretraining and posttraining scores, improvement in performance measures for live cases, and ability to independently handle specimens and operate a microscope. RESULTS: Compared with pretraining, mean posttraining test scores improved by 63% from 48 to 78 out of 100. Mean live case performance score was 95%. Performances improved from 89% on day 1 to 100% on day 2. After training, all endosonographers could independently smear/stain slides and operate a microscope. LIMITATIONS: Long-term impact is unclear. CONCLUSIONS: An intensive 2-day program was effective in training endosonographers in the basics of EUS-related cytopathology. Incorporating basic cytopathology in EUS fellowship curriculum will likely improve diagnostic performance of tissue acquisition procedures. PMID- 25123686 TI - Neuroaxonal dystrophy in Merino-Border Leicester * Polled Dorset lambs. AB - CASE REPORT: The clinicopathological features of neuroaxonal dystrophy (NAD) in 2 lambs are described. Of 40 Merino-Border Leicester * Polled Dorset lambs on a property in north-eastern Victoria, 4 presented with marked ataxia and listlessness, and 2 affected animals (2 days and 2 weeks of age, respectively) of both sexes were necropsied. Numerous axonal swellings (spheroids) were found in the central nervous system, particularly in brainstem nuclei and spinal cord grey matter, and there was severe spinal cord demyelination. CONCLUSIONS: This is the first report of NAD in such crossbred lambs; the affected animals were much younger than in previously described cases of ovine NAD and myelin loss was of much greater magnitude than previously reported. PMID- 25123687 TI - Isolation, identification and characterization of potential impurities in cabazitaxel and their formation. PMID- 25123684 TI - European bats as carriers of viruses with zoonotic potential. AB - Bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies virus, and coronaviruses). While numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in European bats. Although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are conducted. At present, it is assumed that the risk posed by bats to the general public is rather low. In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. All European bat species and their roosts are legally protected and some European species are even endangered. Nevertheless, the increasing public fear of bats and their viruses is an obstacle to their protection. Educating the public regarding bat lyssaviruses might result in reduced threats to both the public and the bats. PMID- 25123689 TI - Mobility Limitation and Changes in Personal Goals Among Older Women. AB - OBJECTIVES: Several theoretical viewpoints suggest that older adults need to modify their personal goals in the face of functional decline. The aim of this study was to investigate longitudinally the association of mobility limitation with changes in personal goals among older women. METHOD: Eight-year follow-up of 205 women aged 66-78 years at baseline. RESULTS: Health-related goals were the most common at both measurements. Goals related to independent living almost doubled and goals related to exercise and to cultural activities substantially decreased during the follow-up. Higher age decreased the likelihood for engaging in new goals related to cultural activities and disengaging from goals related to independent living. Women who had developed mobility limitation during the follow up were less likely to engage in new goals related to exercise and more likely to disengage from goals related to cultural activities and to health and functioning. DISCUSSION: The results of this study support theories suggesting that age-related losses such as mobility limitation may result in older adults modifying or disengaging from personal goals. PMID- 25123688 TI - Age, Rumination, and Emotional Recovery From a Psychosocial Stressor. AB - OBJECTIVES: Exposure to psychosocial stressors often elicits increases in negative affect and blood pressure (BP). Rumination, or thinking about a stressor after it passes, is associated with delayed recovery. Given that older age is associated with greater BP reactivity to psychosocial stressors, rumination may be more detrimental to the recovery of older adults than younger adults. The current study examined this question. We hypothesized that prolonged distress resulting from rumination has greater effects on the recovery of older than younger adults. METHOD: Fifty-two older (M = 69 years) and 61 younger (M = 21 years) adults were exposed to a lab stressor. Afterwards, participants were randomly assigned to a rumination condition (n = 58) or a no-instruction control condition (n = 55). RESULTS: Older participants in the rumination condition had delayed BP recovery relative to those in the control condition and all younger adults. Rumination did not influence affective recovery among any of the groups. DISCUSSION: Rumination delays BP recovery among older adults, suggesting age specific risks associated with different types of emotion regulation strategies. PMID- 25123690 TI - Relationship quality and shared activity in marital and cohabiting dyads in the National Social Life, Health, and Aging Project, Wave 2. AB - OBJECTIVES: This paper introduces scales on shared activity and relationship quality for married and partnered older adults using multiple indicators from the second wave of National Social Life, Health, and Aging Project. METHOD: We assessed the reliability of the scales using Cronbach's alpha and the item-total correlation. We conducted exploratory factor analysis to explore the structure of the items and compared the distribution of each scale means by age group and gender. RESULTS: We found that the relational quality scale has a 2-factor structure, including a positive and negative dimension. The shared activity scale has a 1-factor structure. We found that partnered men show both higher positive and higher negative relationship quality than do partnered women, suggesting that more older men than women experience ambivalent feelings toward their spouse or partner and more women than men have relationships of indifferent quality, with relatively low costs and relatively low benefits. DISCUSSION: The separate conceptualization of shared activity and relationship quality provides one way to examine the dynamic nature of marital quality in later life such as the extent to which shared activities among couples promote or detract from relationships' quality. Analyses for individuals and for dyads are discussed. PMID- 25123691 TI - Australian Idiopathic Pulmonary Fibrosis Registry: vital lessons from a national prospective collaborative project. AB - There is little Australian epidemiologic data on idiopathic pulmonary fibrosis (IPF), a relatively uncommon but devastating disease. The vast geographic distances in Australia have been a major impediment for collaborative research into IPF. A collaborative national effort, the Australian IPF Registry, has been formed, launched and is recruiting successfully (n = 359, January 2014). Our experience provides unique insights for others wishing to set up IPF registries and in time for a global IPF registry. PMID- 25123692 TI - A comprehensive description of postpartum pain after cesarean delivery. AB - OBJECTIVE: To describe women's experiences with the perception of, evaluation of, and response to postpartum pain after cesarean delivery through the sensory, affective, cognitive, and behavioral dimensions of pain. The secondary aim of this research was to differentiate pain described with nociceptive and neuropathic pain descriptors. DESIGN: Longitudinal, concurrent mixed methods design. SETTING: Large, university-based, midwestern medical center. PARTICIPANTS: Convenience sample of 30 low-risk women scheduled for cesarean deliveries. METHODS: The PAINReportIt, a computerized version of the McGill Pain Questionnaire, was administered in person to participants at two visits: between 24 and 48 hours postcesarean delivery and at 6 weeks postpartum. Descriptive statistics, t tests, and chi(2) tests were calculated from these data and pain descriptor selections were compared with established nociceptive and neuropathic pain descriptor lists. RESULTS: Pain was reported in all dimensions at both visits. The abdomen was most frequently selected for pain location; mean intensity was 2.75/10 at the first visit, 1.1/10 at the 6-week visit. Pain in the sensory and cognitive dimensions decreased significantly between visits. Affective dimension pain decreased, but the difference was not significant. Participants reported activities that increased and decreased pain in the behavioral dimension. Pain descriptors indicative of nociceptive (e.g., tender, sore) and neuropathic (e.g. aching) pain were selected at both visits. CONCLUSION: Postpartum pain after cesarean delivery is multidimensional and has been described with words indicative of nociceptive and neuropathic pain. Nurses should complete a thorough and comprehensive pain assessment throughout the postpartum for patients experiencing cesarean deliveries. PMID- 25123693 TI - Evaluation of a rapid bedside scoring system for microcirculation videos acquired from dogs. AB - OBJECTIVE: To appraise a novel scoring system (Bedside Evaluation of Microcirculation [BEM]) to provide qualitative and semiquantitative assessment of canine microcirculatory videos generated by sidestream dark field imaging. DESIGN: Prospective observational study. SETTING: University teaching hospital. ANIMALS: No animals were used in this study. Twenty microcirculatory videos (>20 s in length) acquired from the mucosa adjacent to the upper canine tooth of dogs were selected from a database of sidestream dark field microcirculatory videos with available current standard analysis (CSA). INTERVENTION: Three observers were trained to evaluate 5 video quality parameters (stability, content, illumination, focus, and pressure) and four perfusion parameters (total vessel density [TVD], capillary vessel density [CVD], perfused vessel density [PVD] and microvascular flow index [MFI]). Quality parameters were scored (excellent [0], sufficient [1], and insufficient [2]) similar to CSA recommendations. Each perfusion parameter was subjectively scored (1 lowest - 5 highest) using sample clips from the training video for comparison. Videos passed quality analysis if no parameter was scored insufficient. Repeatability and reproducibility were evaluated by assessing all films in a random order three times daily for 3 days. Strength of correlation of BEM with CSA for both qualitative and semiquantitative parameters was assessed. MEASUREMENTS AND MAIN RESULTS: The qualitative evaluation pass/fail assessment matched CSA 86% of the time with individual observer agreements of 84-88%. Agreement with CSA did not change significantly over the study period (84%, 88%, and 84% on days 1, 2, and 3, respectively). No significant correlations were demonstrated between any BEM perfusion parameter and the corresponding CSA values. CONCLUSIONS: Rapid bedside assessment of microcirculatory video quality can be achieved. However, semiquantitative analysis by BEM demonstrated a lack of correlation with CSA for any of the perfusion parameters assessed. PMID- 25123694 TI - Growing medicine: small-scale cannabis cultivation for medical purposes in six different countries. AB - BACKGROUND: The production and consumption of cannabis for the treatment of medical conditions is of increasing importance internationally; however, research on different aspects of the phenomenon is still scarce. In this article, we report findings from a cross-cultural study of small-scale cannabis cultivation for medical purposes. This kind of comparative study has not been done previously. METHODS: The data were gathered with a help of web surveys conducted by the Global Cannabis Cultivation Research Consortium (GCCRC) in Australia, Belgium, Denmark, Finland, Germany and the UK (N=5313). In the analysis we compare reports of medical motives, for what conditions cannabis is used, whether users have diagnoses for these conditions and whether the use of cannabis been recommended as a treatment of those conditions by a medical doctor. Descriptive statistics are used to show the main commonalities and noteworthy disparities across different countries. RESULTS: Findings from countries were quite similar, even though several national differences in details were found. Growing cannabis for medical purposes was widespread. The majority of medical growers reported cultivating cannabis for serious conditions. Most of them did have a formal diagnosis. One fifth had got a recommendation from their doctor, but in most cases cannabis use was self-medication which was not discussed with their doctors. CONCLUSION: There is a wider demand for licit access for medical cannabis than currently available in these countries. Ideologically, medical growers can be seen distancing themselves from both the legal and illicit drug markets. From a harm reduction perspective, it is worrying that, in the context of present health and control policies in these countries, many medical growers are using cannabis to treat serious medical conditions without proper medical advice and doctor's guidance. PMID- 25123695 TI - United States colorectal cancer screening practices among American Indians/Alaska Natives, blacks, and non-Hispanic whites in the new millennium (2001 to 2010). AB - BACKGROUND: The objectives of this study were to describe, examine, and compare prevalence estimates of colorectal cancer (CRC) screening practices and to determine whether disparities exist for American Indians/Alaska Natives (AIANs) and blacks compared with whites. METHODS: Behavioral Risk Factor Surveillance System (2001-2010) data from respondents aged >= 50 years (n = 356,073) were used. The primary outcome was self-reported CRC screening according to US Preventive Services Task Force guidelines for endoscopy (colonoscopy or sigmoidoscopy), fecal occult blood test (FOBT), or mixed screening (endoscopy or FOBT). RESULTS: From 2001 to 2010, endoscopy screening increased in the AIAN population by 44.8% (P < .001) compared with black respondents (51.7%) and white respondents (26.5%). AIANs were less likely to report endoscopy screening (45%) compared with both blacks (56%) and whites (55%). For mixed CRC screenings, AIAN rates increased by 34.5%, compared with 29.7% for blacks and 15% for whites. In 2010, AIANs (51%) had the lowest prevalence of mixed CRC screening compared with blacks (61%) and whites (60%; P < .001). Factors that enabled health care attenuated the lowered likelihood of CRC screenings, but disparities remained for AIAN CRC screening. In contrast, once enabling factors were controlled, the odds ratios of CRC screening among blacks were higher compared with whites. CONCLUSIONS: Between 2001 and 2010, AIANs had the lowest CRC screening rates in the United States compared with blacks and whites, presenting a CRC disparity, as rigorously defined. The current findings indicate that, although considerable progress has been made to increase CRC screening for blacks and whites, progress for AIANs continues to lag behind in the first decade of 21st century. PMID- 25123696 TI - Cangrelor: a novel intravenous antiplatelet agent with a questionable future. AB - Current percutaneous coronary intervention (PCI) guidelines recommend the use of a P2Y12 inhibitor with aspirin and an injectable anticoagulant. However, available oral P2Y12 inhibitor therapy is limited by significant drug interactions, unclear oral absorption in selected clinical conditions, and delayed onset and offset of activity that may be cumbersome for patients requiring coronary artery bypass graft (CABG) surgery. Cangrelor, a novel intravenous P2Y12 inhibitor, offers potential advantages compared with currently available oral agents, particularly in regard to rapid onset and offset of platelet inhibition. The Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) trials compared cangrelor versus an oral loading dose of clopidogrel, given before or after PCI, in patients with both stable and acute coronary syndromes. The results were conflicting, but some evidence demonstrated a lower rate of stent thrombosis compared with clopidogrel and lower rates of a composite cardiovascular end point, with comparable bleeding rates. The BRIDGE study assessed cangrelor as a replacement for oral P2Y12 inhibitors in patients awaiting CABG surgery and demonstrated that cangrelor maintained platelet inhibition during the preoperative period and enabled a rapid return to baseline platelet function upon cessation of the infusion. A new drug application was submitted to the Food and Drug Administration (FDA) for use during PCI to prevent thrombotic events and as bridging therapy for patients awaiting surgery who require therapy with P2Y12 inhibitors. In February 2014, the FDA's Cardiovascular and Renal Drugs Advisory Committee recommended against approval due to concerns over an appropriate risk-benefit ratio for use during PCI and a lack of evidence supporting the bridging indication. On April 30, 2014, the FDA issued a Complete Response letter for the PCI and bridging indications, denying approval and requesting further data. The future of this once promising novel intravenous antiplatelet agent is now in question. PMID- 25123699 TI - Selective formation and unusual reactivity of tetraarsabicyclo[1.1.0]butane complexes. AB - The selective formation of the dinuclear butterfly complexes [{Cp'''Fe(CO)2}2(MU,eta(1:1)-E4)] (E = P (1 a), As (1 b)) and [{Cp*Cr(CO)3}2(MU,eta(1:1)-E4)] (E = P (2 a), As (2 b)) as new representatives of this rare class of compounds was found by reaction of E4 with the corresponding dimeric carbonyl complexes. Complexes 1 b and 2 b are the first As4 butterfly compounds with a bridging coordination mode. Moreover, first studies regarding the reactivity of 1 b and 2 b are presented, revealing the formation of the unprecedented As8 cuneane complexes [{Cp'''Fe(CO)2}2{Cp'''Fe(CO)}2(MU4,eta(1:1:2:2)-As8)] (3 b) and [{Cp*Cr(CO)3}4(MU4,eta(1:1:1:1)-As8)] (4). The compounds are fully characterized by NMR and IR spectroscopy as well as by X-ray structure analysis. In addition, DFT calculations give insight into the transformation pathway from the E4 butterfly to the corresponding cuneane structural motif. PMID- 25123701 TI - Differential stigmatizing attitudes of healthcare professionals towards psychiatry and patients with mental health problems: something to worry about? A pilot study. AB - PURPOSE: This study compares stigmatizing attitudes of different healthcare professionals towards psychiatry and patients with mental health problems. METHODS: The Mental Illness Clinicians Attitude (MICA) questionnaire is used to assess stigmatizing attitudes in three groups: general practitioners (GPs, n = 55), mental healthcare professionals (MHCs, n = 67) and forensic psychiatric professionals (FPs, n = 53). RESULTS: A modest positive attitude towards psychiatry was found in the three groups (n = 176). Significant differences were found on the total MICA-score (p < 0.001). GPs scored significantly higher than the FPs and the latter scored significantly higher than the MHCs on all factors of the MICA. Most stigmatizing attitudes were found on professionals' views of health/social care field and mental illness and disclosure. Personal and work experience did not influence stigmatizing attitudes. CONCLUSIONS: Although all three groups have a relatively positive attitude using the MICA, there is room for improvement. Bias toward socially acceptable answers cannot be ruled out. Patients' view on stigmatizing attitudes of professionals may be a next step in stigma research in professionals. PMID- 25123703 TI - Clinical approach to endogenous lipoid pneumonia. PMID- 25123702 TI - Diagnostic laparoscopy should be performed before definitive resection for pancreatic cancer: a financial argument. AB - OBJECTIVES: Laparoscopy is recommended to detect radiographically occult metastases in patients with pancreatic cancer before curative resection. This study was conducted to test the hypothesis that diagnostic laparoscopy (DL) is cost-effective in patients undergoing curative resection with or without neoadjuvant therapy (NAT). METHODS: Decision tree modelling compared routine DL with exploratory laparotomy (ExLap) at the time of curative resection in resectable cancer treated with surgery first, (SF) and borderline resectable cancer treated with NAT. Costs (US$) from the payer's perspective, quality adjusted life months (QALMs) and incremental cost-effectiveness ratios (ICERs) were calculated. Base case estimates and multi-way sensitivity analyses were performed. Willingness to pay (WtP) was US$4166/QALM (or US$50,000/quality adjusted life year). RESULTS: Base case costs were US$34,921 for ExLap and US$33,442 for DL in SF patients, and US$39,633 for ExLap and US$39,713 for DL in NAT patients. Routine DL is the dominant (preferred) strategy in both treatment types: it allows for cost reductions of US$10,695/QALM in SF and US$4158/QALM in NAT patients. CONCLUSIONS: The present analysis supports the cost-effectiveness of routine DL before curative resection in pancreatic cancer patients treated with either SF or NAT. PMID- 25123704 TI - An iron oxide nanocarrier for dsRNA to target lymph nodes and strongly activate cells of the immune system. AB - The success of nanoparticle-based therapies will depend in part on accurate delivery to target receptors and organs. There is, therefore, considerable potential in nanoparticles which achieve delivery of the right drug(s) using the right route of administration to the right location at the right time, monitoring the process by non-invasive molecular imaging. A challenge is harnessing immunotherapy via activation of Toll-like receptors (TLRs) for the development of vaccines against major infectious diseases and cancer. In immunotherapy, delivery of the vaccine components to lymph nodes (LNs) is essential for effective stimulation of the immune response. Although some promising advances have been made, delivering therapeutics to LNs remains challenging. It is here shown that iron-oxide nanoparticles can be engineered to combine in a single and small (<50 nm) nanocarrier complementary multimodal imaging features with the immunostimulatory activity of polyinosinic-polycytidylic acid (poly (I:C)). Whilst the fluorescence properties of the nanocarrier show effective delivery to endosomes and TLR3 in antigen presenting cells, MRI/SPECT imaging reveals effective delivery to LNs. Importantly, in vitro and in vivo studies show that, using this nanocarrier, the immunostimulatory activity of poly (I:C) is greatly enhanced. These nanocarriers have considerable potential for cancer diagnosis and the development of new targeted and programmable immunotherapies. PMID- 25123705 TI - A 4-fold-symmetry hexagonal ruthenium for magnetic heterostructures exhibiting enhanced perpendicular magnetic anisotropy and tunnel magnetoresistance. AB - A 4-fold-symmetry hexagonal Ru emerging in epitaxial MgO/Ru/Co2 FeAl/MgO heterostructures is reported, in which an approximately Ru(022-3) growth attributes to the lattice matching between MgO, Ru, and Co2 FeAl. Perpendicular magnetic anisotropy of the Co2 FeAl/MgO interface is substantially enhanced. The magnetic tunnel junctions (MTJs) incorporating this structure give rise to the largest tunnel magnetoresistance for perpendicular MTJs using low damping Heusler alloys. PMID- 25123707 TI - Severe craniosynostosis with Noonan syndrome phenotype associated with SHOC2 mutation: clinical evidence of crosslink between FGFR and RAS signaling pathways. AB - Dysregulation in the RAS signaling cascade results in a family of malformation syndromes called RASopathies. Meanwhile, alterations in FGFR signaling cascade are responsible for various syndromic forms of craniosynostosis. In general, the phenotypic spectra of RASopathies and craniosynostosis syndromes do not overlap. Recently, however, mutations in ERF, a downstream molecule of the RAS signaling cascade, have been identified as a cause of complex craniosynostosis, suggesting that the RAS and FGFR signaling pathways can interact in the pathogenesis of malformation syndromes. Here, we document a boy with short stature, developmental delay, and severe craniosynostosis involving right coronal, bilateral lambdoid, and sagittal sutures with a de novo mutation in exon1 of SHOC2 (c.4A>G p.Ser2Gly). This observation further supports the existence of a crosslink between the RAS signaling cascade and craniosynostosis. In retrospect, the propositus had physical features suggestive of a dysregulated RAS signaling cascade, such as fetal pleural effusion, fetal hydrops, and atrial tachycardia. In addition to an abnormal cranial shape, which has been reported for this specific mutation, craniosynostosis might be a novel associated phenotype. In conclusion, the phenotypic combination of severe craniosynostosis and RASopathy features observed in the propositus suggests an interaction between the RAS and FGFR signaling cascades. Patients with craniosynostosis in combination with any RASopathy feature may require mutation screening for molecules in the FGFR-RAS signaling cascade. PMID- 25123708 TI - Preoperative C-reactive protein and operative blood loss predict poor prognosis in patients with gastric cancer after laparoscopy-assisted gastrectomy. AB - INTRODUCTION: The aim of this study was to clarify the factors associated with postoperative complications and prognoses following laparoscopy-assisted gastrectomy for gastric cancer. METHODS: A total of 214 patients who underwent laparoscopy-assisted gastrectomy for gastric cancer were enrolled in this retrospective study. Factors that were potentially associated with postoperative complications and prognosis were assessed using the following clinical and perioperative parameters: the Estimation of Physiologic Ability and Surgical Stress scoring system, the Prognostic Nutritional Index, and the Clavien-Dindo classification. RESULTS: Postoperative complications developed in 18.7% of patients. Blood loss >= 1% of body weight was significantly correlated with anastomotic leakage (P = 0.0108). Severe complications, based on the Clavien Dindo classification, were more frequent in patients with proximal or total gastrectomies (P = 0.0324). A preoperative C-reactive protein level > 0.5 mg/dL, blood loss > 1% of body weight, age >= 70 years at the time of operation, and an Estimation of Physiologic Ability and Surgical Stress score >= 0.2 were significantly correlated with poor prognosis. Multivariate analysis revealed that two of these factors, preoperative C-reactive protein level >= 0.5 mg/dL and operative blood loss >= 1% of body weight, were independent prognostic factors (P = 0.0376 and P = 0.0112, respectively). The Prognostic Nutritional Index had no significant correlation with prognosis or the occurrence of postoperative complications. CONCLUSION: Operative blood loss >= 1% of body weight and type of resection were associated with an increased frequency of postoperative complications, while preoperative C-reactive protein levels and operative blood loss may be prognostic predictors for gastric cancer patients following laparoscopy-assisted gastrectomy. PMID- 25123706 TI - Role of autonomic reflex arcs in cardiovascular responses to air pollution exposure. AB - The body responds to environmental stressors by triggering autonomic reflexes in the pulmonary receptors, baroreceptors, and chemoreceptors to maintain homeostasis. Numerous studies have shown that exposure to various gases and airborne particles can alter the functional outcome of these reflexes, particularly with respect to the cardiovascular system. Modulation of autonomic neural input to the heart and vasculature following direct activation of sensory nerves in the respiratory system, elicitation of oxidative stress and inflammation, or through other mechanisms is one of the primary ways that exposure to air pollution affects normal cardiovascular function. Any homeostatic process that utilizes the autonomic nervous system to regulate organ function might be affected. Thus, air pollution and other inhaled environmental irritants have the potential to alter both local airway function and baro- and chemoreflex responses, which modulate autonomic control of blood pressure and detect concentrations of key gases in the body. While each of these reflex pathways causes distinct responses, the systems are heavily integrated and communicate through overlapping regions of the brainstem to cause global effects. This short review summarizes the function of major pulmonary sensory receptors, baroreceptors, and carotid body chemoreceptors and discusses the impacts of air pollution exposure on these systems. PMID- 25123710 TI - Female genital mutilation/cutting: will it continue? AB - INTRODUCTION: Female genital mutilation/cutting (FGM/C) is a prevalent, deeply rooted traditional practice in Egypt. AIMS: Specification of the motives behind the continuation of FGM/C in Egyptian community and evaluation of the sexual function in women with FGM/C. METHODS: This cross-sectional study, involved 2,106 sexually active female participants with FGM/C. Full history-taking and general examination to evaluate the type of FGM/C were conducted. Sexual function was assessed by using the Female Sexual Function Index (FSFI) questionnaire. MAIN OUTCOME MEASURES: Enumerate and specify the motivational factors and its percent among the participants. The correlation between FGM/C and FSFI domain scores was done with Pearson's correlation. RESULTS: Tradition, cleanliness, and virginity were the most common motives empowering the continuation of FGM/C (100%), followed by men's wish, esthetic factors, marriage, and religion factors (45.2 100%). Type I FGM/C was the most common, followed by type II. There was only negative correlation between the type II FGM/C and sexual satisfaction. No statistically significant difference between type I and non-FGM/C was found. CONCLUSIONS: FGM/C remains high. A variety of socio-cultural myths, religious misbelievers, and hygienic and esthetic concerns were behind the FGM/C. Overall, a large proportion of the participants supported the continuation of FGM/C in spite of adverse effect and sexual dysfunction associated with FGM/C. PMID- 25123711 TI - Forecast-based interventions can reduce the health and economic burden of wildfires. AB - We simulated public health forecast-based interventions during a wildfire smoke episode in rural North Carolina to show the potential for use of modeled smoke forecasts toward reducing the health burden and showed a significant economic benefit of reducing exposures. Daily and county wide intervention advisories were designed to occur when fine particulate matter (PM2.5) from smoke, forecasted 24 or 48 h in advance, was expected to exceed a predetermined threshold. Three different thresholds were considered in simulations, each with three different levels of adherence to the advisories. Interventions were simulated in the adult population susceptible to health exacerbations related to the chronic conditions of asthma and congestive heart failure. Associations between Emergency Department (ED) visits for these conditions and daily PM2.5 concentrations under each intervention were evaluated. Triggering interventions at lower PM2.5 thresholds (<= 20 MUg/m(3)) with good compliance yielded the greatest risk reduction. At the highest threshold levels (50 MUg/m(3)) interventions were ineffective in reducing health risks at any level of compliance. The economic benefit of effective interventions exceeded $1 M in excess ED visits for asthma and heart failure, $2 M in loss of productivity, $100 K in respiratory conditions in children, and $42 million due to excess mortality. PMID- 25123712 TI - Molecular modeling in dioxane methanol interaction. AB - Molecular interaction between dioxane and methanol involves certain polar and nonpolar bonding to form a one to one complex. Interatomic distances between hydrogen and oxygen within 3 A have been considered as hydrogen bonding. Optimizations of the structures of dioxane-methanol complexes were carried out considering any spatial orientation of a methanol molecule around a chair/boat/twisted-boat conformation of dioxane. From 45 different orientations of dioxane and water, 23 different structures with different local minima were obtained and the structural characteristics like interatomic distances, bond angles, dihedral angles, dipole moment of each complex were discussed. The most stable structure, i.e., with minimum heat of formation is found to have a chair form dioxane, one O-H...O, and two C-H...O hydrogen bonds. In general, the O H...O hydrogen bonds have an average distance of 1.8 A while C-H...O bonds have 2.6 A. The binding energy of the dioxane-methanol complex is found to be a linear function of number of O-H...O and C-H...O bonds, and hydrogen bond length. PMID- 25123714 TI - The Other Side(s) of Health Informatics. PMID- 25123713 TI - Accesses to electronic structures and the excited states of blue luminescent copper(I) complexes containing N-heterocyclic carbene ligands: a DFT/TDDFT exploitation. AB - The ground electronic states and photophysical properties of three designed Cu(I) complexes [Cu(ImNHC)(POP)](+) (1), [Cu(methyl-ImNHC)(POP)](+) (2), and [Cu(BenzImNHC)(POP)](+) (3); where [ImNHC = 3-methyl-1-(pyridin-2-yl)-1H-imidazol 2-ylidene; methyl-ImNHC = 3-methyl-1-(pyridin-2-ylmethyl)-1H-imidazol-2-ylidene; BenzImNHC = 3-methyl-1-(pyridin-2-yl)-1H-benzimidazol-2-ylidene], have been investigated using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results reveal that the presence of the methylene spacer in the NHC ligands has a more direct effect on the distribution of frontier molecular orbitals while the elongation of pi conjugation provided by the fused imidazole in the NHC ligands has a negligible effect. The UV-vis absorption spectra of all the complexes are well produced by TD-DFT calculations based on the charge transfer amount calculations and the corresponding band assignments are discussed. Importantly, the triplet energy calculations demonstrated that complex 2 would be a highly efficient blue emitter with the deep-blue of 440 nm. PMID- 25123715 TI - Francois Gremy, a humanist and information sciences pioneer. PMID- 25123716 TI - Big data in medicine is driving big changes. AB - OBJECTIVES: To summarise current research that takes advantage of "Big Data" in health and biomedical informatics applications. METHODS: Survey of trends in this work, and exploration of literature describing how large-scale structured and unstructured data sources are being used to support applications from clinical decision making and health policy, to drug design and pharmacovigilance, and further to systems biology and genetics. RESULTS: The survey highlights ongoing development of powerful new methods for turning that large-scale, and often complex, data into information that provides new insights into human health, in a range of different areas. Consideration of this body of work identifies several important paradigm shifts that are facilitated by Big Data resources and methods: in clinical and translational research, from hypothesis-driven research to data driven research, and in medicine, from evidence-based practice to practice-based evidence. CONCLUSIONS: The increasing scale and availability of large quantities of health data require strategies for data management, data linkage, and data integration beyond the limits of many existing information systems, and substantial effort is underway to meet those needs. As our ability to make sense of that data improves, the value of the data will continue to increase. Health systems, genetics and genomics, population and public health; all areas of biomedicine stand to benefit from Big Data and the associated technologies. PMID- 25123717 TI - Big Data in Science and Healthcare: A Review of Recent Literature and Perspectives. Contribution of the IMIA Social Media Working Group. AB - OBJECTIVES: As technology continues to evolve and rise in various industries, such as healthcare, science, education, and gaming, a sophisticated concept known as Big Data is surfacing. The concept of analytics aims to understand data. We set out to portray and discuss perspectives of the evolving use of Big Data in science and healthcare and, to examine some of the opportunities and challenges. METHODS: A literature review was conducted to highlight the implications associated with the use of Big Data in scientific research and healthcare innovations, both on a large and small scale. RESULTS: Scientists and health-care providers may learn from one another when it comes to understanding the value of Big Data and analytics. Small data, derived by patients and consumers, also requires analytics to become actionable. Connectivism provides a framework for the use of Big Data and analytics in the areas of science and healthcare. This theory assists individuals to recognize and synthesize how human connections are driving the increase in data. Despite the volume and velocity of Big Data, it is truly about technology connecting humans and assisting them to construct knowledge in new ways. Concluding Thoughts: The concept of Big Data and associated analytics are to be taken seriously when approaching the use of vast volumes of both structured and unstructured data in science and health-care. Future exploration of issues surrounding data privacy, confidentiality, and education are needed. A greater focus on data from social media, the quantified self-movement, and the application of analytics to "small data" would also be useful. PMID- 25123719 TI - Challenges and potential solutions for big data implementations in developing countries. AB - BACKGROUND: The volume of data, the velocity with which they are generated, and their variety and lack of structure hinder their use. This creates the need to change the way information is captured, stored, processed, and analyzed, leading to the paradigm shift called Big Data. OBJECTIVES: To describe the challenges and possible solutions for developing countries when implementing Big Data projects in the health sector. METHODS: A non-systematic review of the literature was performed in PubMed and Google Scholar. The following keywords were used: "big data", "developing countries", "data mining", "health information systems", and "computing methodologies". A thematic review of selected articles was performed. RESULTS: There are challenges when implementing any Big Data program including exponential growth of data, special infrastructure needs, need for a trained workforce, need to agree on interoperability standards, privacy and security issues, and the need to include people, processes, and policies to ensure their adoption. Developing countries have particular characteristics that hinder further development of these projects. CONCLUSIONS: The advent of Big Data promises great opportunities for the healthcare field. In this article, we attempt to describe the challenges developing countries would face and enumerate the options to be used to achieve successful implementations of Big Data programs. PMID- 25123718 TI - Big Data Usage Patterns in the Health Care Domain: A Use Case Driven Approach Applied to the Assessment of Vaccination Benefits and Risks. Contribution of the IMIA Primary Healthcare Working Group. AB - BACKGROUND: Generally benefits and risks of vaccines can be determined from studies carried out as part of regulatory compliance, followed by surveillance of routine data; however there are some rarer and more long term events that require new methods. Big data generated by increasingly affordable personalised computing, and from pervasive computing devices is rapidly growing and low cost, high volume, cloud computing makes the processing of these data inexpensive. OBJECTIVE: To describe how big data and related analytical methods might be applied to assess the benefits and risks of vaccines. METHOD: We reviewed the literature on the use of big data to improve health, applied to generic vaccine use cases, that illustrate benefits and risks of vaccination. We defined a use case as the interaction between a user and an information system to achieve a goal. We used flu vaccination and pre-school childhood immunisation as exemplars. RESULTS: We reviewed three big data use cases relevant to assessing vaccine benefits and risks: (i) Big data processing using crowdsourcing, distributed big data processing, and predictive analytics, (ii) Data integration from heterogeneous big data sources, e.g. the increasing range of devices in the "internet of things", and (iii) Real-time monitoring for the direct monitoring of epidemics as well as vaccine effects via social media and other data sources. CONCLUSIONS: Big data raises new ethical dilemmas, though its analysis methods can bring complementary real-time capabilities for monitoring epidemics and assessing vaccine benefit-risk balance. PMID- 25123720 TI - Technical challenges for big data in biomedicine and health: data sources, infrastructure, and analytics. AB - OBJECTIVES: To review technical and methodological challenges for big data research in biomedicine and health. METHODS: We discuss sources of big datasets, survey infrastructures for big data storage and big data processing, and describe the main challenges that arise when analyzing big data. RESULTS: The life and biomedical sciences are massively contributing to the big data revolution through secondary use of data that were collected during routine care and through new data sources such as social media. Efficient processing of big datasets is typically achieved by distributing computation over a cluster of computers. Data analysts should be aware of pitfalls related to big data such as bias in routine care data and the risk of false-positive findings in high-dimensional datasets. CONCLUSIONS: The major challenge for the near future is to transform analytical methods that are used in the biomedical and health domain, to fit the distributed storage and processing model that is required to handle big data, while ensuring confidentiality of the data being analyzed. PMID- 25123721 TI - Big data - smart health strategies. Findings from the yearbook 2014 special theme. AB - OBJECTIVES: To select best papers published in 2013 in the field of big data and smart health strategies, and summarize outstanding research efforts. METHODS: A systematic search was performed using two major bibliographic databases for relevant journal papers. The references obtained were reviewed in a two-stage process, starting with a blinded review performed by the two section editors, and followed by a peer review process operated by external reviewers recognized as experts in the field. RESULTS: The complete review process selected four best papers, illustrating various aspects of the special theme, among them: (a) using large volumes of unstructured data and, specifically, clinical notes from Electronic Health Records (EHRs) for pharmacovigilance; (b) knowledge discovery via querying large volumes of complex (both structured and unstructured) biological data using big data technologies and relevant tools; (c) methodologies for applying cloud computing and big data technologies in the field of genomics, and (d) system architectures enabling high-performance access to and processing of large datasets extracted from EHRs. CONCLUSIONS: The potential of big data in biomedicine has been pinpointed in various viewpoint papers and editorials. The review of current scientific literature illustrated a variety of interesting methods and applications in the field, but still the promises exceed the current outcomes. As we are getting closer towards a solid foundation with respect to common understanding of relevant concepts and technical aspects, and the use of standardized technologies and tools, we can anticipate to reach the potential that big data offer for personalized medicine and smart health strategies in the near future. PMID- 25123722 TI - Reuse of clinical data. AB - OBJECTIVES: To provide an overview of the benefits of clinical data collected as a by-product of the care process, the potential problems with large aggregations of these data, the policy frameworks that have been formulated, and the major challenges in the coming years. METHODS: This report summarizes some of the major observations from AMIA and IMIA conferences held on this admittedly broad topic from 2006 through 2013. This report also includes many unsupported opinions of the author. RESULTS: The benefits of aggregating larger and larger sets of routinely collected clinical data are well documented and of great societal benefit. These large data sets will probably never answer all possible clinical questions for methodological reasons. Non-traditional sources of health data that are patient-sources will pose new data science challenges. CONCLUSIONS: If we ever hope to have tools that can rapidly provide evidence for daily practice of medicine we need a science of health data perhaps modeled after the science of astronomy. PMID- 25123723 TI - Trends on integrating framework of applications or data. Findings from the section on health and clinical management. AB - OBJECTIVE: To summarize current excellent research and trends in the field of Health and Clinical management. METHODS: Synopsis of the articles selected for the IMIA Yearbook 21014 RESULTS: A comprehensive review of papers published in 2013 was performed by querying PubMed. 1079 were reviewed as papers without authors, without abstract or smaller than 4 pages were excluded from the selection. The editors reviewed all papers and 15 papers selected and provided to to international reviewers. Four papers from international peer-reviewed journals were finally selected for the Health and Clinical Management section. CONCLUSION: Many telemedicine applications are tested nowadays in medical situation, but the challenges emphasized by the best papers selection focus on the ability of proposing integrative frameworks for applications or data in order to handle efficiency of health and clinical management. PMID- 25123725 TI - Human Factors in the Large: Experiences from Denmark, Finland and Canada in Moving Towards Regional and National Evaluations of Health Information System Usability. Contribution of the IMIA Human Factors Working Group. AB - OBJECTIVES: The objective of this paper is to explore approaches to understanding the usability of health information systems at regional and national levels. METHODS: Several different methods are discussed in case studies from Denmark, Finland and Canada. They range from small scale qualitative studies involving usability testing of systems to larger scale national level questionnaire studies aimed at assessing the use and usability of health information systems by entire groups of health professionals. RESULTS: It was found that regional and national usability studies can complement smaller scale usability studies, and that they are needed in order to understand larger trends regarding system usability. Despite adoption of EHRs, many health professionals rate the usability of the systems as low. A range of usability issues have been noted when data is collected on a large scale through use of widely distributed questionnaires and websites designed to monitor user perceptions of usability. CONCLUSION: As health information systems are deployed on a widespread basis, studies that examine systems used regionally or nationally are required. In addition, collection of large scale data on the usability of specific IT products is needed in order to complement smaller scale studies of specific systems. PMID- 25123724 TI - Human factors and health information technology: current challenges and future directions. AB - OBJECTIVES: Recent federal mandates and incentives have spurred the rapid growth, development and adoption of health information technology (HIT). While providing significant benefits for better data integration, organization, and availability, recent reports have raised questions regarding their potential to cause medication errors, decreased clinician performance, and lowered efficiency. The goal of this survey article is to (a) examine the theoretical and foundational models of human factors and ergonomics (HFE) that are being advocated for achieving patient safety and quality, and their use in the evaluation of healthcare systems; (b) and the potential for macroergonomic HFE approaches within the context of current research in biomedical informatics. METHODS: We reviewed literature (2007-2013) on the use of HFE approaches in healthcare settings, from databases such as Pubmed, CINAHL, and Cochran. RESULTS: Based on the review, we discuss the systems-oriented models, their use in the evaluation of HIT, and examples of their use in the evaluation of EHR systems, clinical workflow processes, and medication errors. We also discuss the opportunities for better integrating HFE methods within biomedical informatics research and its potential advantages. CONCLUSIONS: The use of HFE methods is still in its infancy - better integration of HFE within the design lifecycle, and quality improvement efforts can further the ability of informatics researchers to address the key concerns regarding the complexity in clinical settings and develop HIT solutions that are designed within the social fabric of the considered setting. PMID- 25123726 TI - Big Data in Healthcare - Defining the Digital Persona through User Contexts from the Micro to the Macro. Contribution of the IMIA Organizational and Social Issues WG. AB - OBJECTIVES: While big data offers enormous potential for improving healthcare delivery, many of the existing claims concerning big data in healthcare are based on anecdotal reports and theoretical vision papers, rather than scientific evidence based on empirical research. Historically, the implementation of health information technology has resulted in unintended consequences at the individual, organizational and social levels, but these unintended consequences of collecting data have remained unaddressed in the literature on big data. The objective of this paper is to provide insights into big data from the perspective of people, social and organizational considerations. METHOD: We draw upon the concept of persona to define the digital persona as the intersection of data, tasks and context for different user groups. We then describe how the digital persona can serve as a framework to understanding sociotechnical considerations of big data implementation. We then discuss the digital persona in the context of micro, meso and macro user groups across the 3 Vs of big data. RESULTS: We provide insights into the potential benefits and challenges of applying big data approaches to healthcare as well as how to position these approaches to achieve health system objectives such as patient safety or patient-engaged care delivery. We also provide a framework for defining the digital persona at a micro, meso and macro level to help understand the user contexts of big data solutions. CONCLUSION: While big data provides great potential for improving healthcare delivery, it is essential that we consider the individual, social and organizational contexts of data use when implementing big data solutions. PMID- 25123727 TI - Reasons (not) to Spend a Few Billions More on EHRs: How Human Factors Research Can Help. AB - OBJECTIVES: To select best medical informatics research works published in 2013 on electronic health record (EHR) adoption, design, and impact, from the perspective of human factors and organizational issues (HFOI). METHODS: We selected 2,764 papers by querying PubMed (Mesh and TIAB) as well as using a manual search. Papers were evaluated based on pre-defined exclusion and inclusion criteria from their title, keywords, and abstract to select 15 candidate best papers, finally reviewed by 4 external reviewers using a standard evaluation grid. RESULTS: Five papers were selected as best papers to illustrate how human factors approaches can improve EHR adoption and design. Among other contributions, these works: (i) make use of the observational and analysis methodologies of social and cognitive sciences to understand clinicians' attitudes towards EHRs, EHR use patterns, and impact on care processes, workflows, information exchange, and coordination of care; (ii) take into account macro- (environmental) and meso- (organizational) level factors to analyze EHR adoption or lack thereof; (iii) highlight the need for qualitative studies to analyze the unexpected side effects of EHRs on cognitive and work processes as well as the persistent use of paper. CONCLUSION: Selected papers tend to demonstrate that HFOI approaches and methodologies are essential to bridge the gap between EHR systems and end users, and to reduce regularly reported adoption failures and unexpected consequences. PMID- 25123729 TI - Future Direction of IMIA Standardization. Report from the IMIA Standardization Working Group. AB - OBJECTIVES: Standardization in the field of health informatics has increased its importance and global alliance for establishing interoperability and compatibility internationally. Standardization has been organized by standard development organizations (SDOs) such as ISO (International Organization for Standardization), CEN (European Committee for Standardization), IHE (Integrating the Healthcare Enterprise), and HL7 (Health Level 7), etc. This paper reports the status of these SDOs' activities. METHODS: In this workshop, we reviewed the past activities and the current situation of standardization in health care informatics with the standard development organizations such as ISO, CEN, IHE, and HL7. Then we discussed the future direction of standardization in health informatics toward "future medicine" based on standardized technologies. RESULTS: We could share the status of each SDO through exchange of opinions in the workshop. Some WHO members joined our discussion to support this constructive activity. CONCLUSION: At this meeting, the workshop speakers have been appointed as new members of the IMIA working groups of Standards in Health Care Informatics (WG16). We could reach to the conclusion that we collaborate for the international standardization in health informatics toward "future medicine". PMID- 25123731 TI - Big data and smart health strategies: findings from the health information systems perspective. AB - OBJECTIVES: To summarize excellent current research in the field of Health Information Systems. METHOD: Creation of a synopsis of the articles selected for the 2014 edition of the IMIA Yearbook. RESULTS: Four papers from international peer reviewed journals were selected and are summarized. CONCLUSIONS: Selected articles illustrate current research regarding the impact and the evaluation of health information technology and the latest developments in health information exchange. PMID- 25123728 TI - "Big data" and the electronic health record. AB - OBJECTIVES: Implementation of Electronic Health Record (EHR) systems continues to expand. The massive number of patient encounters results in high amounts of stored data. Transforming clinical data into knowledge to improve patient care has been the goal of biomedical informatics professionals for many decades, and this work is now increasingly recognized outside our field. In reviewing the literature for the past three years, we focus on "big data" in the context of EHR systems and we report on some examples of how secondary use of data has been put into practice. METHODS: We searched PubMed database for articles from January 1, 2011 to November 1, 2013. We initiated the search with keywords related to "big data" and EHR. We identified relevant articles and additional keywords from the retrieved articles were added. Based on the new keywords, more articles were retrieved and we manually narrowed down the set utilizing predefined inclusion and exclusion criteria. RESULTS: Our final review includes articles categorized into the themes of data mining (pharmacovigilance, phenotyping, natural language processing), data application and integration (clinical decision support, personal monitoring, social media), and privacy and security. CONCLUSION: The increasing adoption of EHR systems worldwide makes it possible to capture large amounts of clinical data. There is an increasing number of articles addressing the theme of "big data", and the concepts associated with these articles vary. The next step is to transform healthcare big data into actionable knowledge. PMID- 25123733 TI - What Does Big Data Mean for Wearable Sensor Systems? Contribution of the IMIA Wearable Sensors in Healthcare WG. AB - OBJECTIVES: The aim of this paper is to discuss how recent developments in the field of big data may potentially impact the future use of wearable sensor systems in healthcare. METHODS: The article draws on the scientific literature to support the opinions presented by the IMIA Wearable Sensors in Healthcare Working Group. RESULTS: The following is discussed: the potential for wearable sensors to generate big data; how complementary technologies, such as a smartphone, will augment the concept of a wearable sensor and alter the nature of the monitoring data created; how standards would enable sharing of data and advance scientific progress. Importantly, attention is drawn to statistical inference problems for which big datasets provide little assistance, or may hinder the identification of a useful solution. Finally, a discussion is presented on risks to privacy and possible negative consequences arising from intensive wearable sensor monitoring. CONCLUSIONS: Wearable sensors systems have the potential to generate datasets which are currently beyond our capabilities to easily organize and interpret. In order to successfully utilize wearable sensor data to infer wellbeing, and enable proactive health management, standards and ontologies must be developed which allow for data to be shared between research groups and between commercial systems, promoting the integration of these data into health information systems. However, policy and regulation will be required to ensure that the detailed nature of wearable sensor data is not misused to invade privacies or prejudice against individuals. PMID- 25123732 TI - Are electronic cardiac devices still evolving? AB - OBJECTIVES: The goal of this paper is to review some important issues occurring during the past year in Implantable devices. METHODS: First cardiac implantable device was proposed to maintain an adequate heart rate, either because the heart's natural pacemaker is not fast enough, or there is a block in the heart's electrical conduction system. During the last forty years, pacemakers have evolved considerably and become programmable and allow to configure specific patient optimum pacing modes. Various technological aspects (electrodes, connectors, algorithms diagnosis, therapies, ...) have been progressed and cardiac implants address several clinical applications: management of arrhythmias, cardioversion / defibrillation and cardiac resynchronization therapy. RESULTS: Observed progress was the miniaturization of device, increased longevity, coupled with efficient pacing functions, multisite pacing modes, leadless pacing and also a better recognition of supraventricular or ventricular tachycardia's in order to deliver appropriate therapy. Subcutaneous implant, new modes of stimulation (leadless implant or ultrasound lead), quadripolar lead and new sensor or new algorithm for the hemodynamic management are introduced and briefly described. Each times, the main result occurring during the two past years are underlined and repositioned from the history, remaining limitations are also addressed. CONCLUSION: Some important technological improvements were described. Nevertheless, news trends for the future are also considered in a specific session such as the remote follow-up of the patient or the treatment of heart failure by neuromodulation. PMID- 25123730 TI - A Review and Framework for Categorizing Current Research and Development in Health Related Geographical Information Systems (GIS) Studies. AB - OBJECTIVES: The application of GIS in health science has increased over the last decade and new innovative application areas have emerged. This study reviews the literature and builds a framework to provide a conceptual overview of the domain, and to promote strategic planning for further research of GIS in health. METHOD: The framework is based on literature from the library databases Scopus and Web of Science. The articles were identified based on keywords and initially selected for further study based on titles and abstracts. A grounded theory-inspired method was applied to categorize the selected articles in main focus areas. Subsequent frequency analysis was performed on the identified articles in areas of infectious and non-infectious diseases and continent of origin. RESULTS: A total of 865 articles were included. Four conceptual domains within GIS in health sciences comprise the framework: spatial analysis of disease, spatial analysis of health service planning, public health, health technologies and tools. Frequency analysis by disease status and location show that malaria and schistosomiasis are the most commonly analyzed infectious diseases where cancer and asthma are the most frequently analyzed non-infectious diseases. Across categories, articles from North America predominate, and in the category of spatial analysis of diseases an equal number of studies concern Asia. CONCLUSION: Spatial analysis of diseases and health service planning are well-established research areas. The development of future technologies and new application areas for GIS and data gathering technologies such as GPS, smartphones, remote sensing etc. will be nudging the research in GIS and health. PMID- 25123734 TI - Big data, smart homes and ambient assisted living. AB - OBJECTIVES: To discuss how current research in the area of smart homes and ambient assisted living will be influenced by the use of big data. METHODS: A scoping review of literature published in scientific journals and conference proceedings was performed, focusing on smart homes, ambient assisted living and big data over the years 2011-2014. RESULTS: The health and social care market has lagged behind other markets when it comes to the introduction of innovative IT solutions and the market faces a number of challenges as the use of big data will increase. First, there is a need for a sustainable and trustful information chain where the needed information can be transferred from all producers to all consumers in a structured way. Second, there is a need for big data strategies and policies to manage the new situation where information is handled and transferred independently of the place of the expertise. Finally, there is a possibility to develop new and innovative business models for a market that supports cloud computing, social media, crowdsourcing etc. CONCLUSIONS: The interdisciplinary area of big data, smart homes and ambient assisted living is no longer only of interest for IT developers, it is also of interest for decision makers as customers make more informed choices among today's services. In the future it will be of importance to make information usable for managers and improve decision making, tailor smart home services based on big data, develop new business models, increase competition and identify policies to ensure privacy, security and liability. PMID- 25123735 TI - Sensor, signal, and imaging informatics: big data and smart health technologies. AB - OBJECTIVES: This synopsis presents a selection for the IMIA (International Medical Informatics Association) Yearbook 2014 of excellent research in the broad field of Sensor, Signal, and Imaging Informatics published in the year 2013, with a focus on Big Data and Smart Health Technologies Methods: We performed a systematic initial selection and a double blind peer review process to find the best papers in this domain published in 2013, from the PubMed and Web of Science databases. A set of MeSH keywords provided by experts was used. RESULTS: Big Data are collections of large and complex datasets which have the potential to capture the whole variability of a study population. More and more innovative sensors are emerging, allowing to enrich these big databases. However they become more and more challenging to process (i.e. capture, store, search, share, transfer, exploit) because traditional tools are not adapted anymore. CONCLUSIONS: This review shows that it is necessary not only to develop new tools specifically designed for Big Data, but also to evaluate their performance on such large datasets. PMID- 25123736 TI - IBM's Health Analytics and Clinical Decision Support. AB - OBJECTIVES: This survey explores the role of big data and health analytics developed by IBM in supporting the transformation of healthcare by augmenting evidence-based decision-making. METHODS: Some problems in healthcare and strategies for change are described. It is argued that change requires better decisions, which, in turn, require better use of the many kinds of healthcare information. Analytic resources that address each of the information challenges are described. Examples of the role of each of the resources are given. RESULTS: There are powerful analytic tools that utilize the various kinds of big data in healthcare to help clinicians make more personalized, evidenced-based decisions. Such resources can extract relevant information and provide insights that clinicians can use to make evidence-supported decisions. There are early suggestions that these resources have clinical value. As with all analytic tools, they are limited by the amount and quality of data. CONCLUSION: Big data is an inevitable part of the future of healthcare. There is a compelling need to manage and use big data to make better decisions to support the transformation of healthcare to the personalized, evidence-supported model of the future. Cognitive computing resources are necessary to manage the challenges in employing big data in healthcare. Such tools have been and are being developed. The analytic resources, themselves, do not drive, but support healthcare transformation. PMID- 25123737 TI - A 2014 medical informatics perspective on clinical decision support systems: do we hit the ceiling of effectiveness? AB - OBJECTIVE: To summarize recent research and propose a selection of best papers published in 2013 in the field of computer-based decision support in health care. METHOD: Two literature reviews were performed by the two section editors from bibliographic databases with a focus on clinical decision support systems (CDSSs) and computer provider order entry in order to select a list of candidate best papers to be peer-reviewed by external reviewers. RESULTS: The full review process highlighted three papers, illustrating current trends in the domain of clinical decision support. The first trend is the development of theoretical approaches for CDSSs, and is exemplified by a paper proposing the integration of family histories and pedigrees in a CDSS. The second trend is illustrated by well designed CDSSs, showing good theoretical performances and acceptance, while failing to show a clinical impact. An example is given with a paper reporting on scorecards aiming to reduce adverse drug events. The third trend is represented by research works that try to understand the limits of CDSS use, for instance by analyzing interactions between general practitioners, patients, and a CDSS. CONCLUSIONS: CDSSs can achieve good theoretical results in terms of sensibility and specificity, as well as a good acceptance, but evaluations often fail to demonstrate a clinical impact. Future research is needed to better understand the causes of this observation and imagine new effective solutions for CDSS implementation. PMID- 25123738 TI - Managing free text for secondary use of health data. AB - OBJECTIVE: To summarize the best papers in the field of Knowledge Representation and Management (KRM). METHODS: A comprehensive review of medical informatics literature was performed to select some of the most interesting papers of KRM and natural language processing (NLP) published in 2013. RESULTS: Four articles were selected, one focuses on Electronic Health Record (EHR) interoperability for clinical pathway personalization based on structured data. The other three focus on NLP (corpus creation, de-identification, and co-reference resolution) and highlight the increase in NLP tools performances. CONCLUSION: NLP tools are close to being seriously concurrent to humans in some annotation tasks. Their use could increase drastically the amount of data usable for meaningful use of EHR. PMID- 25123739 TI - Transforming health care delivery through consumer engagement, health data transparency, and patient-generated health information. AB - OBJECTIVE: Address current topics in consumer health informatics. METHODS: Literature review. RESULTS: Current health care delivery systems need to be more effective in the management of chronic conditions as the population turns older and experiences escalating chronic illness that threatens to consume more health care resources than countries can afford. Most health care systems are positioned poorly to accommodate this. Meanwhile, the availability of ever more powerful and cheaper information and communication technology, both for professionals and consumers, has raised the capacity to gather and process information, communicate more effectively, and monitor the quality of care processes. CONCLUSION: Adapting health care systems to serve current and future needs requires new streams of data to enable better self-management, improve shared decision making, and provide more virtual care. Changes in reimbursement for health care services, increased adoption of relevant technologies, patient engagement, and calls for data transparency raise the importance of patient-generated health information, remote monitoring, non-visit based care, and other innovative care approaches that foster more frequent contact with patients and better management of chronic conditions. PMID- 25123740 TI - Big Data: Are Biomedical and Health Informatics Training Programs Ready? Contribution of the IMIA Working Group for Health and Medical Informatics Education. AB - OBJECTIVE: The growing volume and diversity of health and biomedical data indicate that the era of Big Data has arrived for healthcare. This has many implications for informatics, not only in terms of implementing and evaluating information systems, but also for the work and training of informatics researchers and professionals. This article addresses the question: What do biomedical and health informaticians working in analytics and Big Data need to know? METHODS: We hypothesize a set of skills that we hope will be discussed among academic and other informaticians. RESULTS: The set of skills includes: Programming - especially with data-oriented tools, such as SQL and statistical programming languages; Statistics - working knowledge to apply tools and techniques; Domain knowledge - depending on one's area of work, bioscience or health care; and Communication - being able to understand needs of people and organizations, and articulate results back to them. CONCLUSION: Biomedical and health informatics educational programs must introduce concepts of analytics, Big Data, and the underlying skills to use and apply them into their curricula. The development of new coursework should focus on those who will become experts, with training aiming to provide skills in "deep analytical talent" as well as those who need knowledge to support such individuals. PMID- 25123741 TI - Engaging Patients through Mobile Phones: Demonstrator Services, Success Factors, and Future Opportunities in Low and Middle-income Countries. AB - OBJECTIVES: Evolving technology and infrastructure can benefit patients even in the poorest countries through mobile health (mHealth). Yet, what makes mobile phone-based services succeed in low and middle-income countries (LMIC) and what opportunities does the future hold that still need to be studied. We showcase demonstrator services that leverage mobile phones in the hands of patients to promote health and facilitate health care. METHODS: We surveyed the recent biomedical literature for demonstrator services that illustrate well-considered examples of mobile phone interventions for consumer health. We draw upon those examples to discuss enabling factors, scalability, reach, and potential of mHealth as well as obstacles in LMIC. RESULTS: Among the 227 articles returned by a PubMed search, we identified 55 articles that describe services targeting health consumers equipped with mobile phones. From those articles, we showcase 19 as demonstrator services across clinical care, prevention, infectious diseases, and population health. Services range from education, reminders, reporting, and peer support, to epidemiologic reporting, and care management with phone communication and messages. Key achievements include timely adherence to treatment and appointments, clinical effectiveness of treatment reminders, increased vaccination coverage and uptake of screening, and capacity for efficient disease surveillance. We discuss methodologies of delivery and evaluation of mobile-phone-based mHealth in LMIC, including service design, social context, and environmental factors to success. CONCLUSION: Demonstrated promises using mobile phones in the poorest countries encourage a future in which IMIA takes a lead role in leveraging mHealth for citizen empowerment through Consumer Health Informatics. PMID- 25123742 TI - Social media and patient health outcomes. Findings from the yearbook 2014 section on consumer health informatics. AB - OBJECTIVES: To provide a review of the current excellent research published in the field of Consumer Health Informatics. METHOD: We searched MEDLINE(r) and WEB OF SCIENCE(r) databases for papers published in 2013 in relation with Consumer Health Informatics. The authors identified 16 candidate best papers, which were then reviewed by four reviewers. RESULTS: Five out of the 16 candidate papers were selected as best papers. One paper presents the key features of a system to automate the collection of web-based social media content for subsequent semantic annotation. This paper emphasizes the importance of mining social media to collect novel data from which new findings in drug abuse research were uncovered. The second paper presents a practical method to predict how a community structure would impact the spreading of information within the community. The third paper presents a method for improving the quality of online health communities. The fourth presents a new social network to allow the monitoring of the evolution of individuals' health status and diagnostic deficiencies, difficulties or barriers in rehabilitation. The last paper reports on teenage patients' perception on privacy and social media. CONCLUSION: Selected papers not only show the value of using social media in the medical field but how to use these media to detect emergent diseases or risks, inform patients, promote disease prevention, and follow patients' opinion on healthcare resources. PMID- 25123744 TI - EHR Big Data Deep Phenotyping. Contribution of the IMIA Genomic Medicine Working Group. AB - OBJECTIVES: Given the quickening speed of discovery of variant disease drivers from combined patient genotype and phenotype data, the objective is to provide methodology using big data technology to support the definition of deep phenotypes in medical records. METHODS: As the vast stores of genomic information increase with next generation sequencing, the importance of deep phenotyping increases. The growth of genomic data and adoption of Electronic Health Records (EHR) in medicine provides a unique opportunity to integrate phenotype and genotype data into medical records. The method by which collections of clinical findings and other health related data are leveraged to form meaningful phenotypes is an active area of research. Longitudinal data stored in EHRs provide a wealth of information that can be used to construct phenotypes of patients. We focus on a practical problem around data integration for deep phenotype identification within EHR data. The use of big data approaches are described that enable scalable markup of EHR events that can be used for semantic and temporal similarity analysis to support the identification of phenotype and genotype relationships. CONCLUSIONS: Stead and colleagues' 2005 concept of using light standards to increase the productivity of software systems by riding on the wave of hardware/processing power is described as a harbinger for designing future healthcare systems. The big data solution, using flexible markup, provides a route to improved utilization of processing power for organizing patient records in genotype and phenotype research. PMID- 25123745 TI - Managing large-scale genomic datasets and translation into clinical practice. AB - OBJECTIVE: To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain. METHOD: We provide a synopsis of the articles selected for the IMIA Yearbook 2014, from which we attempt to derive a synthetic overview of current and future activities in the field. A first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor evaluated independently the set of 1,851 articles and 15 articles were retained for peer-review. RESULTS: The selection and evaluation process of this Yearbook's section on Bioinformatics and Translational Informatics yielded three excellent articles regarding data management and genome medicine. In the first article, the authors present VEST (Variant Effect Scoring Tool) which is a supervised machine learning tool for prioritizing variants found in exome sequencing projects that are more likely involved in human Mendelian diseases. In the second article, the authors show how to infer surnames of male individuals by crossing anonymous publicly available genomic data from the Y chromosome and public genealogy data banks. The third article presents a statistical framework called iCluster+ that can perform pattern discovery in integrated cancer genomic data. This framework was able to determine different tumor subtypes in colon cancer. CONCLUSIONS: The current research activities still attest the continuous convergence of Bioinformatics and Medical Informatics, with a focus this year on large-scale biological, genomic, and Electronic Health Records data. Indeed, there is a need for powerful tools for managing and interpreting complex data, but also a need for user-friendly tools developed for the clinicians in their daily practice. All the recent research and development efforts are contributing to the challenge of impacting clinically the results and even going towards a personalized medicine in the near future. PMID- 25123747 TI - Information technology for clinical, translational and comparative effectiveness research. Findings from the section clinical research informatics. AB - OBJECTIVE: To select and summarize key contributions to current research in the field of Clinical Research Informatics (CRI). METHOD: A bibliographic search using a combination of MeSH and free terms search over PubMed was performed followed by a blinded review. RESULTS: The review process resulted in the selection of four papers illustrating various aspects of current research efforts in the area of CRI. The first paper tackles the challenge of extracting accurate phenotypes from Electronic Healthcare Records (EHRs). Privacy protection within shared de-identified, patient-level research databases is the focus of the second selected paper. Two other papers exemplify the growing role of formal representation of clinical data - in metadata repositories - and knowledge - in ontologies - for supporting the process of reusing data for clinical research. CONCLUSIONS: The selected articles demonstrate how concrete platforms are currently achieving interoperability across clinical research and care domains and have reached the evaluation phase. When EHRs linked to genetic data have the potential to shift the research focus from research driven patient recruitment to phenotyping in large population, a key issue is to lower patient re identification risks for biomedical research databases. Current research illustrates the potential of knowledge engineering to support, in the coming years, the scientific lifecycle of clinical research. PMID- 25123748 TI - Cardiovascular disease: the leap towards translational and clinical proteomics. PMID- 25123749 TI - Prof. Michael (Mike) J. Dunn--paying forward. PMID- 25123746 TI - Clinical research informatics and electronic health record data. AB - OBJECTIVES: The goal of this survey is to discuss the impact of the growing availability of electronic health record (EHR) data on the evolving field of Clinical Research Informatics (CRI), which is the union of biomedical research and informatics. RESULTS: Major challenges for the use of EHR-derived data for research include the lack of standard methods for ensuring that data quality, completeness, and provenance are sufficient to assess the appropriateness of its use for research. Areas that need continued emphasis include methods for integrating data from heterogeneous sources, guidelines (including explicit phenotype definitions) for using these data in both pragmatic clinical trials and observational investigations, strong data governance to better understand and control quality of enterprise data, and promotion of national standards for representing and using clinical data. CONCLUSIONS: The use of EHR data has become a priority in CRI. Awareness of underlying clinical data collection processes will be essential in order to leverage these data for clinical research and patient care, and will require multi-disciplinary teams representing clinical research, informatics, and healthcare operations. Considerations for the use of EHR data provide a starting point for practical applications and a CRI research agenda, which will be facilitated by CRI's key role in the infrastructure of a learning healthcare system. PMID- 25123743 TI - Surveying Recent Themes in Translational Bioinformatics: Big Data in EHRs, Omics for Drugs, and Personal Genomics. AB - OBJECTIVE: To provide a survey of recent progress in the use of large-scale biologic data to impact clinical care, and the impact the reuse of electronic health record data has made in genomic discovery. METHOD: Survey of key themes in translational bioinformatics, primarily from 2012 and 2013. RESULT: This survey focuses on four major themes: the growing use of Electronic Health Records (EHRs) as a source for genomic discovery, adoption of genomics and pharmacogenomics in clinical practice, the possible use of genomic technologies for drug repurposing, and the use of personal genomics to guide care. CONCLUSION: Reuse of abundant clinical data for research is speeding discovery, and implementation of genomic data into clinical medicine is impacting care with new classes of data rarely used previously in medicine. PMID- 25123754 TI - Reply to magnetic resonance imaging-based diagnosis of progressive multifocal leukoencephalopathy in a patient with non-Hodgkin lymphoma after therapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab. PMID- 25123753 TI - The neuroprotective potential of sinapic acid in the 6-hydroxydopamine-induced hemi-parkinsonian rat. AB - Parkinson's disease (PD) is a neurodegenerative movement disorder due to selective loss of dopaminergic neurons of mesencephalic substantia nigra pars compacta (SNC) with debilitating motor symptoms. Current treatments for PD afford symptomatic relief with no prevention of disease progression. Due to the antioxidant and neuroprotective potential of sinapic acid, this study was conducted to evaluate whether this agent could be of benefit in an experimental model of early PD in rat. Unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesioned rats were pretreated p.o. with sinapic acid at doses of 10 or 20 mg/kg. One week after surgery, apomorphine caused significant contralateral rotations, a significant reduction in the number of Nissl-stained and tyrosine hydroxylase (TH)-positive neurons and a significant increase of iron reactivity on the left side of SNC. Meanwhile, malondialdehyde (MDA) and nitrite levels in midbrain homogenate significantly increased and activity of superoxide dismutase (SOD) significantly reduced in the 6-OHDA-lesioned group. In addition, sinapic acid at a dose of 20 mg/kg significantly improved turning behavior, prevented loss of SNC dopaminergic neurons, lowered iron reactivity, and attenuated level of MDA and nitrite. These results indicate the neuroprotective potential of sinapic acid against 6-OHDA neurotoxicity that is partially due to the attenuation of oxidative stress and possibly lowering nigral iron level. PMID- 25123758 TI - Implant therapy: 40 years of experience. AB - Implant placement has become a well-established and highly successful therapy in the rehabilitation of partially and fully edentulous patients. The 'original' treatment protocol, which aimed to demonstrate implant 'biocompatibility' and the achievement of osseointegration, has evolved over the past 40 years into a broader treatment approach in which the esthetic and patient-related objectives have become the main focus. This volume of Periodontology 2000 summarizes, via narrative reviews, the advantages and disadvantages of this evolution in implantology and offers recommendations on where and when to apply the new therapeutic protocols, without jeopardizing the outcome for the patient. It also discusses current treatments of the most common implant-associated complications. Many of the implant innovations and new therapeutic protocols are supported by evidence-based knowledge and have provided clear benefits for both the patient and the clinician. PMID- 25123756 TI - Comment on 'Genetic evidence and new morphometric data as essential tools to identify the Patagonian seahorse Hippocampus patagonicus (Pisces, Syngnathidae) by Gonzalez et al. (2014)'. PMID- 25123757 TI - Genotypic alteration and competitive nodulation of Mesorhizobium muleiense against exotic chickpea rhizobia in alkaline soils. AB - Mesorhizobium muleiense, Mesorhizobium mediterraneum and Mesorhizobium ciceri are chickpea (Cicer arietinum L.) rhizobia that share a high similarity of the symbiotic genes nodC and nifH, but they have different geographic distributions. M. muleiense has been isolated and found only in alkaline soils of Xinjiang, China, whereas the other two strains have been found in the Mediterranean and India. To investigate the species stability of M. muleiense during natural evolution and its capability of competitive nodulation against the other two exotic species, re-sampling of nodules in the field and competition experiments between the three species were conducted. The results showed that the predominant microsymbiont associated with chickpea grown in Xinjiang was still M. muleiense, but the predominant genotypes of M. muleiense had changed significantly during the four years since a previous survey. The data also showed that M. mediterraneum and M. ciceri were more competitive than the residential strain of M. muleiense CCBAU 83963(T) in sterilized vermiculite or soils from Xinjiang. However, in non-sterilized soils, M. muleiense was the predominant nodule occupier. These results indicated that natural or adapting evolution of M. muleiense was occurring in fields subjected to changing environmental factors. In addition, the biogeography and symbiotic associations of rhizobia with their host legumes were also influenced by biological factors in the soil, such as indigenous rhizobia and other organisms. PMID- 25123755 TI - The degree of retinopathy is equally predictive for renal and macrovascular outcomes in the ACCORD Trial. AB - AIMS: Diabetic retinopathy (DR) is associated with a higher risk of renal and cardiovascular events. We sought to compare the risk for renal versus cardiovascular (CV) outcomes, stratified by retinopathy severity. METHODS: ACCORD was a randomized trial of people with type 2 diabetes, at high-risk for CV disease. A subgroup (n=3,369 from 71 clinics) had stereoscopic fundus photographs graded centrally. Participants were stratified at baseline to moderate/severe DR or no/mild DR and were monitored for renal and CV outcomes at follow-up visits over 4 years. The composite renal outcome was composed of serum creatinine doubling, macroalbuminuria, or end-stage renal disease. The composite CV outcome was the ACCORD trial primary outcome. Competing risk techniques were used to estimate the relative risk (RR) of renal versus CV composite outcomes within each DR stratum. RESULTS: The hazards ratio for doubling of serum creatinine and incident CV event in the moderate/severe DR versus no/mild DR strata were: 2.31 (95% CI: 1.25-4.26) and 1.98 (95% CI: 1.49-2.62), respectively. The RR of the two composite outcomes was highly similar in the no/mild DR stratum (adjusted RR at 4 years for CV versus renal events=0.96, 95% CI: 0.72-1.28) and the moderate/severe DR stratum (adjusted RR=0.92, 95% CI: 0.64-1.31). CONCLUSIONS: Thus, in people with type 2 diabetes at high risk for cardiovascular disease, incident CV versus renal events was similar, irrespective of the severity of the DR. Further evaluation of the specificity of DR for microvascular versus macrovascular events in other populations is warranted. PMID- 25123759 TI - Horizontal bone augmentation by means of guided bone regeneration. AB - The development of bone augmentation procedures has allowed placement of dental implants into jaw bone areas lacking an amount of bone sufficient for standard implant placement. Thus, the indications for implants have broadened to include jaw regions with bone defects and those with a bone anatomy that is unfavorable for implant anchorage. Of the different techniques, the best documented and the most widely used method to augment bone in localized alveolar defects is guided bone regeneration. A large body of evidence has demonstrated the successful use of guided bone regeneration to regenerate missing bone at implant sites with insufficient bone volume and the long-term success of implants placed simultaneously with, or after, guided bone regeneration. However, the influence of guided bone regeneration on implant survival and success rates, and the long term stability of the augmented bone, remain unknown. Many of the materials and techniques currently available for bone regeneration of alveolar ridge defects were developed many years ago. Recently, various new materials and techniques have been introduced. Many of them have, however, not been sufficiently documented in clinical studies. The aim of this review was to present the scientific basis of guided bone regeneration and the accepted clinical procedures. A classification of bone defects has been presented, aiming at simplifying the decision-making process regarding the choice of strategy for bone augmentation. Finally, an outlook into actual research and the possible future options related to bone augmentation has been provided. PMID- 25123760 TI - Zygomatic implants: indications, techniques and outcomes, and the zygomatic success code. AB - The zygoma implant has been an effective option in the management of the atrophic edentulous maxilla as well as for maxillectomy defects. Branemark introduced the zygoma implant not only as a solution to obtain posterior maxillary anchorage but also to expedite the rehabilitation process. The zygoma implant is a therapeutic option that deserves consideration in the treatment-planting process. This paper reviews the indications for zygoma implants and the surgical and prosthetic techniques (including new developments) and also reports on the clinical outcome of the zygomatic anatomy-guided approach. An overview of conventional grafting procedures is also included. Finally, a Zygoma Success Code, describing specific criteria to score the success of rehabilitation anchored on zygomatic implants, is proposed. PMID- 25123762 TI - Short implant in limited bone volume. AB - Rehabilitation of severely resorbed jaws with dental implants remains a surgical and prosthetic challenge for clinicians. The purpose of this review was to evaluate the available data on short-length implants and discuss their indications and limitations in daily clinical practice. A structured review of MEDLINE and a manual search were conducted. Thirty-two case series devoted to short-length implants, 14 reviews and 3 randomized controlled trials were identified. Of this group of papers, we can conclude that short-length implants can be successfully used to support single and multiple fixed reconstructions in posterior atrophied jaws, even in those with increased crown-to-implant ratios. The use of short-length implants allows treatment of patients who are unable to undergo complex surgical techniques for medical, anatomic or financial reasons. Moreover, the use of short-length implants in daily clinical practice reduces the need for complex surgeries, thus reducing morbidity, cost and treatment time. The use of short implants promotes the new concept of stress-minimizing surgery, allowing the surgeon to focus more on the correct three-dimensional positioning of the implant. PMID- 25123763 TI - Critical buccal bone dimensions along implants. AB - The buccal bone plate is a component of the alveolar process tightly related to the tooth it supports. A plethora of physiological and pathological events can induce its remodeling. Understanding this remodeling process and its extent is of major importance for the practitioner as it can affect the functional and esthetic outcome of implant surgery at the involved sites. Bone remodeling and resorption of the buccal bone plate are inevitable after tooth loss or extraction. To limit resorption, several ridge-preservation techniques of varying efficacy have been described. Bone resorption is equally found to occur upon implant placement and is thought to be a result of the surgical trauma inflicted as well as an adaptation process of the tissues to the new foreign body. Because of the implications of bone resorption on the soft-tissue levels and the general esthetic outcome, it is of primary importance for the practitioner to be able to evaluate the hard tissues and the inherent resorption risks in an effort to optimize the treatment strategies. Based on limited short-term data, the present general opinion advises the need for a 2-mm-thick buccal bone plate in order to avoid vertical bone resorption. PMID- 25123761 TI - Sinus floor elevation utilizing the transalveolar approach. AB - A transalveolar approach for sinus floor elevation with subsequent placement of dental implants was first suggested by Tatum in 1986. In 1994, Summers described a different transalveolar approach using a set of tapered osteotomes with increasing diameters. The transalveolar approach of sinus floor elevation, also referred to as 'osteotome sinus floor elevation', the 'Summers technique' or the 'Crestal approach', may be considered as being more conservative and less invasive than the conventional lateral window approach. This is reflected by the fact that more than nine out of 10 patients who experienced the surgical procedure would be willing to undergo it again. The main indication for transalveolar sinus floor elevation is reduced residual bone height, which does not allow standard implant placement. Contraindications for transalveolar sinus floor elevation may be intra-oral, local or medical. The surgical approach utilized over the last two decades is the technique described by Summers, with or without minor modifications. The surgical care after implant placement using the osteotome technique is similar to the surgical care after standard implant placement. The patients are usually advised to take antibiotic prophylaxis and to utilize antiseptic rinses. The main complications reported after performing a transalveolar sinus floor elevation were perforation of the Schneiderian membrane in 3.8% of patients and postoperative infections in 0.8% of patients. Other complications reported were postoperative hemorrhage, nasal bleeding, blocked nose, hematomas and benign paroxysmal positional vertigo. Whether it is necessary to use grafting material to maintain space for new bone formation after elevating the sinus membrane utilizing the osteotome technique is still controversial. Positive outcomes have been reported with and without using grafting material. A prospective study, evaluating both approaches, concluded that significantly more bone gain was seen when grafting material was used (4.1 mm mean bone gain compared with 1.7 mm when no grafting material was utilized). In a systematic review, including 19 studies reporting on 4388 implants inserted using the transalveolar sinus floor elevation technique, the 3-year implant survival rate was 92.8% (95% confidence interval: 87.4-96.0%). Furthermore, a subject-based analysis of the same material revealed an annual failure rate of 3.7%. Hence, one in 10 subjects experienced implant loss over 3 years. Several of the included studies demonstrated that transalveolar sinus floor elevation was most predictable when the residual alveolar bone height was >= 5 mm and the sinus floor anatomy was relatively flat. PMID- 25123764 TI - Critical soft-tissue dimensions with dental implants and treatment concepts. AB - Dental implants have proven to be a successful treatment option in fully and partially edentulous patients, rendering long-term functional and esthetic outcomes. Various factors are crucial for predictable long-term peri-implant tissue stability, including the biologic width; the papilla height and the mucosal soft-tissue level; the amounts of soft-tissue volume and keratinized tissue; and the biotype of the mucosa. The biotype of the mucosa is congenitally set, whereas many other parameters can, to some extent, be influenced by the treatment itself. Clinically, the choice of the dental implant and the position in a vertical and horizontal direction can substantially influence the establishment of the biologic width and subsequently the location of the buccal mucosa and the papilla height. Current treatment concepts predominantly focus on providing optimized peri-implant soft-tissue conditions before the start of the prosthetic phase and insertion of the final reconstruction. These include refined surgical techniques and the use of materials from autogenous and xenogenic origins to augment soft-tissue volume and keratinized tissue around dental implants, thereby mimicking the appearance of natural teeth. PMID- 25123765 TI - Implant-assisted complete prostheses. AB - The current review was undertaken to obtain a better understanding of the knowledge base of implant-assisted complete dental prostheses (fixed and removable) in the treatment of the completely edentulous maxilla or mandible. Indications, advantages and disadvantages, complications and maintenance issues, as well as the cost-effectiveness of both treatments, are discussed to help clinicians in their therapeutic decision-making. In summary, when indicated and depending on the patients' needs, both removable and fixed implant-assisted prostheses are highly safe, reliable and satisfactory treatment modalities for the rehabilitation of edentulous jaws. Careful and precise treatment planning is highly recommended to assist the clinician in preventing potential prosthetic failures. The review also reveals that there is still a need for data, generated using robust research methods, on some patient-based and clinical outcomes. PMID- 25123766 TI - Immediate implants at fresh extraction sockets: from myth to reality. AB - In recent years, immediate implant placement has become a common clinical therapeutic protocol representing an alternative to the classical delayed surgical protocol of implant placement. This protocol, however, has not been fully validated, either in terms of fully understanding the influence of implant placement on the socket-healing process or on the clinical outcomes. This narrative review evaluates the different experimental studies in humans and animals assessing the bone-healing dynamics of the socket after tooth extraction and the dimensional changes occurring at the socket bone walls. These experimental studies describe, in detail, the hard- and soft-tissue healing of implants placed into fresh extraction sockets, demonstrating that marked morphological changes of the alveolar ridge will occur, independently of the implant installation, thus demonstrating that postextraction bone loss is an inevitable biological process. This evidence has also been corroborated in clinical studies in humans, demonstrating the risk of significant peri-implant tissue loss, mainly in the areas of high esthetic demand. There is a lack of long term evidence on the impact of this protocol on the preservation of the peri implant tissues. In conclusion, despite the obvious advantages of this surgical protocol, it also has limitations and is more technically demanding than placing an implant into a healed crest. When selecting this protocol, clinicians should always consider: (a) the gingival biotype of the patient; (b) the thickness and integrity of the socket bony walls; (c) the implant selection as well as the adequate vertical and horizontal position of the implant; and (d) the ideal patient (a nonsmoker with good plaque control). PMID- 25123767 TI - Immediate loading in partially and completely edentulous jaws: a review of the literature with clinical guidelines. AB - The introduction of immediate loading was a paradigm shift in implant dentistry as it was previously believed that an unloaded period was essential for bone healing in order to promote osseointegration. However, this belief could not be confirmed by clinical studies or by human histology. Hitherto, numerous reports have been published on immediate loading in various indications. An important factor for success is primary implant stability. The latter can be improved by adapting drilling protocols to enhance lateral compression of the bone and by using tapered implant designs with apical thread fixation. To some extent, the use of implants with a microrough surface and rigid splinting may compensate for suboptimal stability. It is important to avoid fracture of the provisional restoration at all times as this may result in local overloading and implant failure. Also, unevenly distributed occlusal contacts may contribute to failure and therefore occlusion ought to be evaluated at every occasion, especially during the early phase of healing. Taking these aspects into account, immediate loading in the fully edentulous mandible by means of an overdenture has been shown to be predictable in terms of implant survival (94.4-100%). However, the procedure may result in additional costs as a result of the need for repeated relining. In addition, the scientific basis for this treatment concept in the maxilla is very scarce. Immediate loading in the fully edentulous jaw by means of a fixed prosthesis is a well-documented treatment concept. In the mandible, three implants have been shown to be insufficient, given the failure rate of up to 10%. With at least four implants a failure rate of 0-3.3% may be expected. In the maxilla, four to six implants could be too limited, given the failure rate up to 7.2%. Increasing the number of implants may reduce implant failure to 3.3%. Provisional fixed prostheses are particularly prone to fracture in the maxilla and hence reinforcement is warranted. Immediately loaded single implants have lower survival rates, of 85.7-100%, with no clear impact of occlusal contact. In fact, a meta-analysis demonstrated a five times higher risk of failure for immediately loaded single implants when compared with delayed loading. No study showed superior soft-tissue preservation or esthetics following immediate loading of single implants compared with other loading protocols. However, this finding may not imply that a provisional implant crown becomes redundant when soft-tissue conditioning is deemed necessary. Taking into account earlier factors for success, immediate loading in the partially edentulous jaw by means of a fixed prosthesis seems predictable in terms of implant survival (95.5-100%). However, there are no studies with data on soft-tissue parameters, esthetic aspects or patient-centered outcomes, and the available studies mainly relate to the load carrying part of the dentition. Clinical studies focusing on these aspects of treatment outcome are clearly needed. High patient satisfaction is the most important advantage of immediate loading, especially during the early healing phase. In this context, one should also realize that studies have revealed comparable patient satisfaction in patients following delayed loading once their prosthesis is in place. In the decision-making process, this aspect should be properly discussed with the patient along with other advantages and disadvantages of immediate loading. PMID- 25123768 TI - Neurovascular disturbances after implant surgery. AB - With a steadily increasing impact of oral implant placement in daily practice, the number of reported surgical complications has also been growing. Recent studies reveal significant variation in the occurrence and morphology of neurovascular canal structures in the jaw bone. All those structures contain a neurovascular bundle, the diameter of which may be large enough to cause clinically significant damage. Therefore, it has become obvious that presurgical radiographic planning of jaw-bone surgery should pay attention to the neurovascular structures and their likely variations, in addition to examining many other factors, such as jaw-bone morphology and volume, bone trabecular structure and the absence of bone or tooth pathology. A critical review is accomplished to explore the potential risks for neurovascular complications after implant placement, with evidence derived from histologic, anatomic, clinical and radiologic studies. In this respect, cross-sectional imaging can often be advocated, as it is obvious that the inherent three-dimensional nature of jaw bone anatomy may clearly benefit from a detailed spatial image analysis. Although this could initially be realized by conventional computed tomography, in current practice, dentomaxillofacial cone beam computed tomography might be used, as it offers high-quality images at low radiation dose levels and costs. PMID- 25123769 TI - Dental cone beam computed tomography: justification for use in planning oral implant placement. AB - Intra-oral and panoramic radiographs are most frequently used in oral health care. Yet, the inherent nature of jaws and teeth renders three-dimensional diagnosis essential, especially in relation to oral surgery. Nowadays, this can be accomplished by dental cone beam computed tomography, which provides high quality images at low radiation doses and low costs. Nonetheless, the effective dose ranges of cone beam computed tomography machines may easily vary from 10 to 1000 MUSv, this being equivalent to two to 200 panoramic radiographs, even for similar presurgical indications. Moreover, the diagnostic image quality varies massively among available machines and parameter settings. Apart from the radiodiagnostic possibilities, dental cone beam computed tomography may offer a vast therapeutic potential, including opportunities for surgical guidance and further prosthetic rehabilitation via computer-aided design/computer-aided manufacturing solutions. These additional options may definitely explain part of the success of cone beam computed tomography for oral implant placement. In conclusion, dental cone beam computed tomography imaging could be justified for oral implant-related diagnosis, planning and transfer to surgical and further prosthetic treatment, but guidelines for justification and cone beam computed tomography optimization remain mandatory. PMID- 25123770 TI - Different techniques of static/dynamic guided implant surgery: modalities and indications. AB - For computer-guided surgery a static surgical guide is used that transfers the virtual implant position from computerized tomographic data to the surgical site. These guides are produced by computer-aided design/computer-assisted manufacture technology, such as stereolithography, or manually in a dental laboratory (using mechanical positioning devices or drilling machines). With computer-navigated surgery the position of the instruments in the surgical area is constantly displayed on a screen with a three-dimensional image of the patient. In this way, the system allows real-time transfer of the preoperative planning and visual feedback on the screen. A workflow of the different systems is presented in this review. PMID- 25123771 TI - Guided surgery: accuracy and efficacy. AB - Different computer-assisted implant-placement procedures are currently available. These differ in software, template manufacture, guiding device, stabilization and fixation. The literature seems to indicate that one has to accept a certain inaccuracy of +/-2.0 mm, which seems large initially but is clearly smaller than for nonguided surgery. A reduction of accuracy to below 0.5 mm seems extremely difficult. A common shortcoming identified in the studies included in this review is inconsistency in how clinical data and outcome variables are reported. Another limitation is the small number of comparative clinical studies. In order to find the best guiding system or the most important parameters for optimal accuracy, more randomized clinical trials are necessary. Information on cost-effectiveness and patient-centered evaluations (i.e. questionnaires and interviews) must also be included. PMID- 25123772 TI - Etiology and treatment of periapical lesions around dental implants. AB - The widespread use of oral implants in recent years has resulted in various types of complications. One of those complications is the periapical implant lesion. Different factors have been proposed to play a role in the development and emergence of a periapical implant lesion. To date, there is no consensus on the etiology and therefore periapical lesions around dental implants are considered to have a multifactorial etiology. The diagnosis of an implant periapical lesion should be based on both clinical and radiological findings. Additionally, in order to apply the best treatment strategy the evolution of the lesion should be taken into account. The treatment of this kind of lesion, however, is still empiric. Data, primarily from case reports, seem to indicate that the removal of all granulation tissue is a first step to arrest the progression of the bone destruction. The removal of the apical part of the implant seems a valuable treatment strategy. PMID- 25123773 TI - Management of peri-implant mucositis and peri-implantitis. AB - Peri-implant diseases are defined as inflammatory lesions of the surrounding peri implant tissues and include peri-implant mucositis (an inflammatory lesion limited to the surrounding mucosa of an implant) and peri-implantitis (an inflammatory lesion of the mucosa that affects the supporting bone with resulting loss of osseointegration). This review aims to describe the different approaches to manage both entities and to provide a critical evaluation of the evidence available on their efficacy. Therapy of peri-implant mucositis and nonsurgical therapy of peri-implantitis usually involve mechanical debridement of the implant surface using curettes, ultrasonic devices, air-abrasive devices or lasers, with or without the adjunctive use of local antibiotics or antiseptics. The efficacy of these therapies has been demonstrated for mucositis: controlled clinical trials show an improvement in clinical parameters, especially in bleeding on probing. For peri-implantitis, the results are limited, especially in terms of probing pocket-depth reduction. Surgical therapy of peri-implantitis is indicated when nonsurgical therapy fails to control the inflammatory changes. Selection of the surgical technique should be based on the characteristics of the peri-implant lesion. In the presence of deep circumferential and intrabony defects, surgical interventions should aim to provide thorough debridement, implant-surface decontamination and defect reconstruction. In the presence of defects without clear bony walls or with a predominant suprabony component, the aim of the surgical intervention should be the thorough debridement and the repositioning of the marginal mucosa to enable the patient to perform effective oral-hygiene practices, although this aim may compromise the esthetic result of the implant supported restoration. PMID- 25123774 TI - Optimizing multiple-choice tests as tools for learning. AB - Answering multiple-choice questions with competitive alternatives can enhance performance on a later test, not only on questions about the information previously tested, but also on questions about related information not previously tested-in particular, on questions about information pertaining to the previously incorrect alternatives. In the present research, we assessed a possible explanation for this pattern: When multiple-choice questions contain competitive incorrect alternatives, test-takers are led to retrieve previously studied information pertaining to all of the alternatives in order to discriminate among them and select an answer, with such processing strengthening later access to information associated with both the correct and incorrect alternatives. Supporting this hypothesis, we found enhanced performance on a later cued-recall test for previously nontested questions when their answers had previously appeared as competitive incorrect alternatives in the initial multiple-choice test, but not when they had previously appeared as noncompetitive alternatives. Importantly, however, competitive alternatives were not more likely than noncompetitive alternatives to be intruded as incorrect responses, indicating that a general increased accessibility for previously presented incorrect alternatives could not be the explanation for these results. The present findings, replicated across two experiments (one in which corrective feedback was provided during the initial multiple-choice testing, and one in which it was not), thus strongly suggest that competitive multiple-choice questions can trigger beneficial retrieval processes for both tested and related information, and the results have implications for the effective use of multiple-choice tests as tools for learning. PMID- 25123775 TI - Israel-Gaza conflict. PMID- 25123776 TI - Israel-Gaza conflict. PMID- 25123777 TI - Letter in support of Richard Horton. PMID- 25123778 TI - Risk factors and early origins of chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease is mainly a smoking-related disorder and affects millions of people worldwide, with a large effect on individual patients and society as a whole. Although the disease becomes clinically apparent around the age of 40-50 years, its origins can begin very early in life. Different risk factors in very early life--ie, in utero and during early childhood--drive the development of clinically apparent chronic obstructive pulmonary disease in later life. In discussions of which risk factors drive chronic obstructive pulmonary disease, it is important to realise that the disease is very heterogeneous and at present is largely diagnosed by lung function only. In this Review, we will discuss the evidence for risk factors for the various phenotypes of chronic obstructive pulmonary disease during different stages of life. PMID- 25123779 TI - Concordance and discordance in patient and provider perceptions of dizziness. AB - PURPOSE: The purpose of the present investigation was to determine whether there are significant differences in patient/healthcare provider perceptions of patient's dizziness severity, dizziness disability/handicap, anxiety, and signs of autonomic system activation. MATERIALS AND METHODS: This was a prospective investigation of 30 patient-provider dyads drawn as a sample of convenience from an otology clinic in a large, tertiary care, medical center. Patients completed both the Dizziness Handicap Inventory (DHI) and the Vestibular Symptom Scale (VSS) prior to vestibular function testing. Providers were instructed to complete the same measures following the patient's clinic visit from what they estimated was the patient's point of view. The two measures were analyzed for concordance and discordance. RESULTS: Patient/provider differences in DHI and VSS vertigo subscale scores were not significantly different. However, difference scores on the VSS anxiety/autonomic subscale indicated that providers significantly under estimated patient anxiety and symptoms of autonomic system activation. CONCLUSIONS: The results suggest that providers may be missing information pertinent to the role anxiety and autonomic system activation may play in patient visits for complaints of dizziness. We suggest that this problem can be mitigated by administrating to patients prior to their clinic visit a standardized measure that quantifies patient self-report dizziness, vertigo, anxiety and autonomic system arousal. Patterns of response by patients on these measures can enable providers to diagnose correctly dizziness disorders that are rooted in clinically significant anxiety either related to, or unrelated to, a history of vestibular system impairment. PMID- 25123780 TI - Pediatric mandibular reconstruction following resection of oral squamous cell carcinoma: a case report. AB - PURPOSE: Squamous cell carcinoma is a common entity among adult head and neck cancer patients, with many requiring reconstruction post resection. Conversely, this entity is rare among children with major reconstruction even more unique. This case and the concomitant review of literature highlight the intricacies of pediatric facial reconstruction. METHODS: The case described is of a 6-year-old African-American boy with poor dentition and a painful, 1.5 cm epiphytic lesion on the alveolar ridge of the left mandible. Incisional biopsy and computerized tomography were employed to obtain diagnosis and extent of disease. Surgical resection and reconstruction followed. RESULTS: Incisional biopsy confirmed the diagnosis of squamous cell carcinoma. Maxillofacial computerized tomography confirmed the extent of the mandibular lesion. After interdisciplinary discussion and weighing options with the family, a segmental mandibulectomy, neck dissection, and right fibula free flap reconstruction with titanium 2.0 mm metal plate fixation was performed. Re-examination post-operatively showed complete coverage of the defect and the ability to restore excised dentition. CONCLUSION: Squamous cell carcinoma within the pediatric population occurs less often than sarcomas, but may necessitate major reconstruction. Without rigid reconstruction, contracture may result. The current consensus favors microvascular bone reconstruction. However, a lack of consensus exists regarding the timing of dental rehabilitation. PMID- 25123781 TI - The AGREE Enterprise: a decade of advancing clinical practice guidelines. AB - BACKGROUND: The original AGREE (Appraisal of Guidelines for REsearch and Evaluation) Instrument was published in 2003, and its revision, the AGREE II, in 2009. Together, they filled an important gap in the guideline and quality of care fields. Ten years later, the AGREE Enterprise reflects on a trajectory of projects and international collaboration that have contributed to advancing the science and quality of practice guidelines and the uptake of AGREE/AGREE II. FINDINGS: The AGREE Enterprise has undertaken activities to improve the tool and to develop resources to support its use. Since 2003, the uptake and adoption of AGREE by the international community has been swift and broad. A total of 33 language translations of the original AGREE Instrument and the current AGREE II are available and were initiated by the international community. A recent scan of the published literature identified over 600 articles that referenced the AGREE tools. The AGREE tools have been widely received and applied, with several organizations having incorporated the AGREE as part of their formal practice guideline programs. Since its redevelopment in 2010, the AGREE Enterprise website (www.agreetrust.org) continues to experience steady increases in visitors per month and currently has over 10,000 registered users. CONCLUSIONS: The AGREE Enterprise has contributed to the advancements of guidelines through research activities and international participation by scientific and user communities. As we enter a new decade, we look forward to ongoing collaborations and contributing to further advancements to improve quality of care and health care systems. PMID- 25123783 TI - An ab initio study of the thermoelectric enhancement potential in nano-grained TiNiSn. AB - Novel approaches for the development of highly efficient thermoelectric materials capable of a direct conversion of heat into electricity, are being constantly investigated. TiNiSn based half-Heusler alloys exhibit a high thermoelectric potential for practical, renewable power generation applications. The main challenge of further enhancement of the thermoelectric efficiency of these alloys lies in the reduction of the associated high lattice thermal conductivity values without adversely affecting the electronic transport properties. The current manuscript theoretically investigates two possible routes for overcoming this limitation in TiNiSn alloys. On the one hand, the influence of nano-grained structure of TiNiSn on the electronic structure of the material is theoretically demonstrated. On the other hand, the potential for thermal conductivity reduction upon increasing the Ni fraction in the intermetallic TiNiSn compound via the formation of metallic TiNi2Sn nanoparticles is also shown. Using the applied approach, a useful route for optimizing both the electronic and thermal properties of half-Heusler TiNiSn, for practical thermoelectric applications, is demonstrated. PMID- 25123782 TI - Differentiation of bland from neoplastic thrombus of the portal vein in patients with hepatocellular carcinoma: application of susceptibility-weighted MR imaging. AB - BACKGROUND: Neoplastic and bland portal vein thrombi (PVT) are both common in patients with hepatocellular carcinoma (HCC). The correct discrimination of them is essential for therapeutic strategies planning and survival predicting. The current study aims to investigate the value of susceptibility-weighted imaging (SWI) in differentiating bland from neoplastic PVT in HCC patients. METHODS: 20 HCC patients with bland PVT and 22 HCC patients with neoplastic PVT were imaged with non-contrast SWI at 3.0 Tesla MRI. The signal intensity (SI) of the PVT and HCC lesions in the same patients was compared on SW images. The phase values of the PVT were compared between neoplastic and bland thrombi cohorts. Receiver operator characteristics (ROC) analysis was conducted to evaluate the diagnostic ability of the phase values for neoplastic and bland thrombi discrimination. RESULTS: 20 of 22 neoplastic PVT were judged similar SI and 2 were judged lower SI than their HCC. For 20 bland PVT, 19 were judged lower SI and 1 was judged similar SI as their HCC (P<0.001). The average phase values (0.361 +/- 0.224) of the bland PVT were significantly higher than those of the neoplastic PVT (-0.328 +/- 0.127, P<0.001). The AUC for phase values in differentiating bland from neoplastic PVT was 0.989. The best cut-off value was -0.195, which gave a sensitivity of 95% and a specificity of 95.5%. CONCLUSIONS: SW imaging appears to be a promising new method for distinguishing neoplastic from bland PVT. The high sensitivity and specificity suggest its high value in clinical practice. PMID- 25123784 TI - Weight loss after participation in a national VA weight management program among veterans with or without PTSD. AB - OBJECTIVE: This evaluation compared the effectiveness of MOVE!, a U.S. Veterans Health Administration (VHA) weight management program, among veterans with posttraumatic stress disorder (PTSD), other mental conditions, or no mental health diagnoses. METHODS: VHA administrative data from 2008 to 2012 were used to estimate adjusted six- and 12-month weight change and >=5% weight loss among 20,819 veterans with "intense and sustained" MOVE! participation (14% of 148,963 MOVE! participants, regardless of mental health status). RESULTS: Compared with veterans with no mental health diagnoses, veterans with PTSD lost significantly less weight at six and 12 months (p<.05) and were less likely to lose >=5% body weight at six months (OR=.89, p<.05). At six months, those with other mental conditions lost significantly less weight than those with no mental health diagnoses (p<.05). CONCLUSIONS: MOVE! may need adaptation to increase overall engagement and enhance weight loss for veterans with mental conditions, especially PTSD. PMID- 25123785 TI - Morphological and thermodynamic comparison of the lesions created by 4 open irrigated catheters in 2 experimental models. AB - INTRODUCTION: New generation open-irrigated catheters aim to improve irrigation efficiency. This may change lesion patterns, challenging operators. Indeed, safety issues have recently arisen. We aimed to experimentally assess 4 open irrigated catheters, comparing lesion size, safety, and heat transfer. METHODS: The thigh lesion model was employed in 6 anesthetized pigs to assess the morphology of perpendicular and tangential lesions (n = 140) created by the newer catheters ThermoCool(r) SF, CoolFlexTM, and BlazerTM Open-Irrigated, and the standard ThermoCool(r), at a constant power of 30 W (60 seconds). To evaluate the propensity for deep-tissue overheating, a set of 120 applications were performed at 50 W (180 seconds) comparing pop rates. Thermal assessment of the lesion generation process (20 W, 60 seconds, n = 32) was performed with an infrared camera on bovine ventricular tissue. RESULTS: At 30 W, the newer catheters showed lower temperature readings compared with the ThermoCool(r). No major efficacy or safety differences were found at tangential applications; however, at perpendicular applications: (1) the SF at 17 mL/min better preserved the superficial layers and focused its maximum thermal effect deeper, but at recommended flow rates (8 mL/min) it generated the largest superficial lesions; (2) CoolFlexTM created smaller lesions than SF and readily induced steam pops at 50 W without temperature control; and (3) no major differences were found comparing BlazerTM Open-Irrigated and ThermoCool(r). CONCLUSIONS: The lower temperature readings in the newer catheters make them more prone to deliver the maximum programmed power. Under experimental conditions, the SF catheter focuses its maximum effect deeper and the CoolFlexTM can be more prone to induce steam pops at high power settings. PMID- 25123786 TI - Stricter indications are recommended for fenestration surgery in intracranial arachnoid cysts of children. AB - PURPOSE: The indication of surgical treatment for intracranial arachnoid cysts (ACs) is a controversial issue. In this study, we reviewed surgical outcomes of intracranial ACs that were treated with endoscopic fenestration or microscopic fenestration, which are currently standard practices for surgical treatment of AC. In addition, we also evaluated the validity of current surgical indications. METHODS: We analyzed pediatric patients under 18 years of age who underwent surgical management for intracranial AC between January 2000 and December 2011. Patients with a follow-up period of less than 1 year were excluded. A total of 75 patients were enrolled in this study. These patients were assessed by subjective symptoms and by a clinician's objective evaluation. The radiological assessment of AC after surgery was also evaluated. RESULTS: The median age of patients at the initial operation was 5 years. The median follow-up period was 38 months. The goal of surgery was achieved in 28% (21/75) of patients. The radiological alteration of AC after initial fenestration surgery was diverse. The results of the clinical and radiological assessments did not always coincide. A total of 35 complications occurred in 28 patients. Subdural fluid collection was the most common unexpected radiological complication. CONCLUSIONS: Our study showed that the fenestration procedure for AC produced unsatisfactory clinical improvements compared to the relatively high complication rate. Therefore, surgical treatment for AC should be strictly limited to patients who have symptoms directly related to AC. PMID- 25123788 TI - Effects of dispersant used for oil spill remediation on nitrogen cycling in Louisiana coastal salt marsh soil. AB - On April 20, 2010, the BP Deepwater Horizon (DWH) offshore oil platform experienced an explosion which triggered the largest marine oil spill in US history. Approximately 7.9 million liters of dispersant, Corexit EC9500A, was used during the spill between May 15th and July 12th. Marsh soil samples were collected from an unimpacted marsh site proximal to coastal areas that suffered light to heavy oiling for a laboratory evaluation to determine the effect of Corexit on the wetland soil microbial biomass as well as N-mineralization and denitrification rates. Microbial biomass nitrogen (N) values were below detection for the 1:10, 1:100 and 1:1000 Corexit:wet soil treatments. The potentially mineralizable N (PMN) rate correlated with microbial biomass with significantly lower rates for the 1:10 and 1:100 Corexit:wet soil additions. Potential denitrification rates for Corexit:wet soil ratios after immediate dispersant exposure were below detection for the 1:10 treatment, while the 1:100 was 7.6+/ 2.7% of the control and the 1:1000 was 33+/-4.3% of the control. The 1:10000 treatment was not significantly different from the control. Denitrification rates measured after 2 weeks exposure to the surfactant found the 1:10 treatment still below detection limit and the 1:100 ratio was 12+/-2.6% of the control. Results from this lab study suggest that chemical dispersants have the potential to negatively affect the wetland soil microbial biomass and resultant microbial activity. Consequences of exposure led to reductions in several important microbial-regulated ecosystem services including water quality improvement (denitrification) and ecosystem primary productivity (N-mineralization). Future studies should investigate the longer-term impacts of dispersant exposure on the microbial consortia to determine if microbial activity recovers over time. PMID- 25123787 TI - Alternative polyadenylation regulates CELF1/CUGBP1 target transcripts following T cell activation. AB - Alternative polyadenylation (APA) is an evolutionarily conserved mechanism for regulating gene expression. Transcript 3' end shortening through changes in polyadenylation site usage occurs following T cell activation, but the consequences of APA on gene expression are poorly understood. We previously showed that GU-rich elements (GREs) found in the 3' untranslated regions of select transcripts mediate rapid mRNA decay by recruiting the protein CELF1/CUGBP1. Using a global RNA sequencing approach, we found that a network of CELF1 target transcripts involved in cell division underwent preferential 3' end shortening via APA following T cell activation, resulting in decreased inclusion of CELF1 binding sites and increased transcript expression. We present a model whereby CELF1 regulates APA site selection following T cell activation through reversible binding to nearby GRE sequences. These findings provide insight into the role of APA in controlling cellular proliferation during biological processes such as development, oncogenesis and T cell activation. PMID- 25123789 TI - Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver. AB - Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP) 1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase 2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. PMID- 25123790 TI - Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory response, but not apoptosis in mouse: the prevention of curcumin. AB - This study investigated the protective effects of curcumin on tetrachloro-p benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS, COX-2, IL-1beta, IL-6, TNF-alpha and NF-kappaB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling. PMID- 25123791 TI - Designed modulation of sex steroid signaling inhibits telomerase activity and proliferation of human prostate cancer cells. AB - The predominant estrogen-receptor (ER)-beta signaling in normal prostate is countered by increased ER-alpha signaling in prostate cancer (CaP), which in association with androgen-receptor (AR) signaling results in pathogenesis of the disease. However CaP treatments mostly target AR signaling which is initially effective but eventually leads to androgen resistance, hence simultaneous targeting of ERs has been proposed. A novel series of molecules were designed with multiple sex-steroid receptor modulating capabilities by coalescing the pharmacophores of known anti-CaP molecules that act via modulation of ER(alpha/beta) and/or AR, viz. 3,3'diindolylmethane (DIM), mifepristone, toremifene, tamoxifen and raloxifene. N,N-diethyl-4-((2-(4-methoxyphenyl)-1H indol-3-yl)methyl) aniline (DIMA) was identified as the most promising structure of this new series. DIMA increased annexin-V labelling, cell-cycle arrest and caspase-3 activity, and decreased expression of AR and prostate specific antigen in LNCaP cells, in vitro. Concurrently, DIMA increased ER-beta, p21 and p27 protein levels in LNCaP cells and exhibited ~5 times more selective binding for ER-beta than ER-alpha, in comparison to raloxifene. DIMA exhibited a dose dependent ER-beta agonism and ER-alpha antagonism in classical gene reporter assay and decreased hTERT (catalytic subunit of telomerase) transcript levels in LNCaP at 3.0 MUM (P<0.05). DIMA also dose-dependently decreased telomerase enzyme activity in prostate cancer cells. It is thus concluded that DIMA acts as a multi steroid receptor modulator and effectively inhibits proliferation of prostate cancer cells through ER-beta mediated telomerase inhibition, by countering actions of ER-alpha and AR. Its unique molecular design can serve as a lead structure for generation of potent agents against endocrine malignancies like the CaP. PMID- 25123792 TI - Acute kidney injury in critical care: experience of a conservative strategy. AB - PURPOSE: Renal replacement therapy (RRT) is a major supportive treatment of acute kidney injury (AKI) in intensive care unit (ICU), but the timing of its initiation remains open to debate. MATERIALS AND METHODS: We retrospectively analyzed ICU patients who had AKI associated with at least one usual RRT criteria: serum creatinine concentration greater than 300 MUmol/L, serum urea concentration greater than 25 mmol/L, serum potassium concentration greater than 6.5 mmol/L, severe metabolic acidosis (arterial blood pH<7.2), oliguria (urine output<135 mL/8 hours or <400 mL/24 hours), overload pulmonary edema. To estimate the risk of death associated with RRT adjusted for risk factors, we performed a marginal structural Cox model with inverse-probability-of-treatment-weighted estimator. RESULTS: Among 4173 patients admitted to the ICU, 203 patients fulfilled potential RRT criteria. Ninety-one patients (44.8%) received RRT and 112 (55.2%) did not. Non-RRT and RRT patients differed in terms of severity of illness: Simplified Acute Physiology Score II (55+/-17 vs 60+/-19, respectively; P<.05) and Sequential Organ Failure Assessment score (8 [5-10] vs 9 [7-11], respectively; P=.01). Crude analysis indicated a lower ICU mortality for non-RRT compared with RRT patients (18% vs 45%; P<.001). In the marginal structural Cox model, RRT was associated with increased mortality (P<.01). CONCLUSION: A conservative approach of AKI was not associated with increased mortality. PMID- 25123793 TI - Neurocritical care complications of pregnancy and puerperum. AB - Neurocritical care complications of pregnancy and puerperum such as preeclampsia/eclampsia, hemolysis, elevated liver enzymes, low platelets syndrome, thrombotic thrombocytopenic purpura, seizures, ischemic and hemorrhagic stroke, postpartum angiopathy, cerebral sinus thrombosis, amniotic fluid emboli, choriocarcinoma, and acute fatty liver of pregnancy are rare but can be devastating. These conditions can present a challenge to physicians because pregnancy is a unique physiologic state, most therapeutic options available in the intensive care unit were not studied in pregnant patients, and in many situations, physicians need to deliver care to both the mother and the fetus, simultaneously. Timely recognition and management of critical neurologic complications of pregnancy/puerperum can be life saving for both the mother and fetus. PMID- 25123794 TI - Intensivist perceptions of family-centered rounds and its impact on physician comfort, staff involvement, teaching, and efficiency. AB - PURPOSE: Our goal was to examine intensivists' perception of comfort, staff satisfaction, teaching, and efficiency with family-centered rounds (FCR). MATERIALS AND METHODS: Surveys were sent to intensivists at Emory University. Responses of physicians that participate in FCR were compared with those who do not. Survey questions were developed using a 5-point Likert scale with 1 representing a negative response and 5 being positive. RESULTS: Of 46 surveys sent, there were 31 responses (response rate, 67%). Seventeen responses were from adult intensivists and 14 from pediatric. Sixteen respondees (52%) participate in FCR, whereas 15 respondents (48%) do not. There is a significant difference in physician comfort with the practice with an average score of 4.4+1.0 for those who participate and 2.7+1.7 for those who do not (P=.002). There is also a significant difference in the perception of the impact of FCR on staff. Those who participate feel that it has a significantly greater positive impact on staff's involvement during rounds with an average score of 3.6+1.2 vs an average score of 2.3+1.2 for those who do not practice FCR (P=.003). Those who participate in FCR have significantly more positive perception on its impact on patient outcomes with an average score of 3.8+1.1 compared with an average score of 2.9+1.3 for those who do not participate in FCR (P=.05). There are no significant differences in perceptions on teaching and efficiency among participants and nonparticipants in FCR. CONCLUSIONS: Participation in FCR is associated with an increase in perceived physician comfort, positive impact on staff involvement, and positive impact on patient outcome. Concerns over teaching and efficiency remain. PMID- 25123798 TI - The relationship between revascularization extent and the long-term prognosis of patients with stable angina pectoris and three-vessel disease treated by percutaneous coronary intervention in the era of drug-eluting stents. AB - BACKGROUND: The effects of revascularization extent (RE) on the long-term prognosis of patients with stable angina pectoris and 3-vessel disease who underwent percutaneous coronary intervention were unknown. HYPOTHESIS: The study was aimed at evaluating whether there was an effect of RE on patients presenting with stable angina pectoris and 3-vessel disease. METHODS: RE, which was calculated by baseline SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score minus residue SYNTAX score divided by baseline SYNTAX score, was initially used in our study. Five hundred fifty-eight patients presenting with stable angina pectoris and 3-vessel disease were assigned to and compared among tertiles according to RE and clinical outcomes. The primary end point was the major adverse cardiovascular event (MACE), a composite of cardiac death, nonfatal myocardial infarction (MI), and any repeat revascularization. RESULTS: The median follow-up period was 56.9 months (interquartile range, 52.1-63.6). The incidence of MACE increased significantly as RE increased (13.3%, 31.4%, and 44.1%, log-rank P < 0.001). The same tendency was observed in occurrences of target-vessel failure (TVF) (a composite of cardiac death, MI, or target-vessel revascularization) (8.8%, 20.3%, and 28.4%, log-rank P < 0.001), repeat revascularization (11.8%, 26.2%, and 35.6%, log-rank P < 0.001), and MI (1.1%, 2.9%, and 12.6%, log-rank P < 0.001). Multivariate analysis confirmed the tendencies mentioned above. CONCLUSIONS: For patients presenting with stable angina pectoris and 3-vessel disease, the increasing extent of revascularization resulted in a less favorable prognosis. PMID- 25123799 TI - [Laparoscopic liver surgery]. AB - Liver resection remains the method of choice for curative treatment for liver tumors. Development in diagnostic and surgical techniques has improved operative results as well as long-term outcomes. In the last decade minimally invasive laparoscopic (LAP) surgery has been increasingly adopted by liver units. The trend in LAP liver resection has been moving from limited resections towards major hepatectomy. This process, however, is relatively slow, which can be due to technical difficulties of the procedure and fear of haemorrhage. Despite having a hard time at the start, major resections become more common. Up to now approximately 6000 LAP liver resections were performed worldwide, number of major hepatectomies is estimated between 700-800. LAP liver resections are feasible with significant benefits for patients consisting of less blood loss, less narcotic requirements, and shorter hospital stay with comparable postoperative morbidity and mortality to open liver resections. It is an accepted management of both benign and malignant liver lesions. There is no difference between LAP and open surgery in late survival after resection for colorectal liver metastases. Overall survival of LAP resected hepatocellular carcinoma cases seems to be superior compared with open surgery. PMID- 25123797 TI - Differential infection outcome of Chlamydia trachomatis in human blood monocytes and monocyte-derived dendritic cells. AB - BACKGROUND: Chlamydia trachomatis is an intracellular bacteria which consist of three biovariants; trachoma (serovars A-C), urogenital (serovars D-K) and lymphogranuloma venereum (L1-L3), causing a wide spectrum of disease in humans. Monocytes are considered to disseminate this pathogen throughout the body while dendritic cells (DCs) play an important role in mediating immune response against bacterial infection. To determine the fate of C. trachomatis within human peripheral blood monocytes and monocyte-derived DCs, these two sets of immune cells were infected with serovars Ba, D and L2, representative of the three biovariants of C. trachomatis. RESULTS: Our study revealed that the different serovars primarily infect monocytes and DCs in a comparable fashion, however undergo differential infection outcome, serovar L2 being the only candidate to inflict active infection. Moreover, the C. trachomatis serovars Ba and D become persistent in monocytes while the serovars predominantly suffer degradation within DCs. Effects of persistence gene Indoleamine 2, 3-dioxygenase (IDO) was not clearly evident in the differential infection outcome. The heightened levels of inflammatory cytokines secreted by the chlamydial infection in DCs compared to monocytes seemed to be instrumental for this consequence. The immune genes induced in monocytes and DCs against chlamydial infection involves a different set of Toll-like receptors, indicating that distinct intracellular signalling pathways are adopted for immune response. CONCLUSION: Our results demonstrate that the host pathogen interaction in chlamydia infection is not only serovar specific but manifests cell specific features, inducing separate immune response cascade in monocytes and DCs. PMID- 25123800 TI - [Is daily chest X-ray necessary after lung resection? Evidence-based decision making]. AB - OBJECTIVES: The 'gold standard' practice following insertion of a chest tube after lobectomy is daily chest radiography (CXR), but this is not always followed. We compared the outcomes associated with the use of these two methods in our practice. METHODS: Data from 148 patients who underwent uncomplicated lobectomies with insertion of one chest drain were analysed. In the routine CXR group (R-CXR) (50 patients), an immediate postoperative CXR, daily routine radiography during the drainage period, and one after surgical drain removal were performed. In the symptomatic CXR group (S-CXR) (98 patients), a CXR was performed only for symptomatic patients (fever, hypoxia, subcutaneous emphysema, air leak) and/or a single radiograph was taken after surgical drain removal. The following postoperative data were compared: fever, CXR abnormalities (pneumothorax, fluid, atelectasis, subcutaneous emphysema, haematoma), number of radiographs, drainage time, and new drain insertion. RESULTS: The mean chest tube duration was 3.7 and 3.8 days in the R-CXR and S-CXR groups, respectively. Abnormal CXRs after surgical drain removal were reported in 50% (25/50) and 46.9% (46/96) (p = 0.724) of patients in the R-CXR and S-CXR groups, respectively, but new drain insertion was only necessary in 3/25 (12%) and 7/46 (15.2%) of these cases. The mean number of CXRs for each patient was 5.0 and 2.3 (p = 0.0001) in the R-CXR and S-CXR groups, respectively. CONCLUSIONS: If CXRs are limited to symptomatic patients then the number of radiographs can be reduced by around 50%. There were no more postoperative complications or abnormal final CXR findings if the CXR was only ordered for symptomatic patients instead of as 'daily routine' during the postoperative period. Only 12-15% of the CXR abnormalities required surgical intervention. PMID- 25123801 TI - [Outcomes following rectal and recto-sigmoid cancer resections: comparison of the laparoscopic and open techniques]. AB - BACKGROUND/AIMS: Surgical technique and experience are considered as significant determinants of the successful treatment of recto-sigmoid malignancies. METHODS: Two hundred patients operated on between 2005 and 2009 were prospectively followed with an average of 39.8 months. Patients with rectosigmoid or rectal cancer were included, either with primary resection or resection after neoadjuvant therapy. The primary aim was to assess the average survival in the two groups; secondary outcomes were stage specific survival and the incidence of loco-regional recurrence and distant metastases. Intra- and postoperative complications, operating time, onco-pathological specimen quality and length of stay were also analysed. RESULTS: During the follow-up comparable rates for 3 year survival and recurrence rates were found without statistical difference. Hospital stay in the laparoscopic group was significantly shorter and the mid term survival rates were also better in the more advanced stages. Incisional hernia rate was significantly lower in the laparoscopic group. CONCLUSIONS: The results of laparoscopic rectal and recto-sigmoid resections were not inferior, and - in some aspects - they were even better compared to open procedures. Adding the properties of the minimally invasive technique (shorter recovery, reduced surgical stress reaction) this should be the preferred method of operative approach. PMID- 25123802 TI - [Massive localized lymphoedema (MLL) in the mons pubis]. AB - Massive localized lymphoedema (MLL) is a relatively frequent complication in obesity. MLL is present as a giant swelling and associated with characteristic skin changes. Due to the pathologic and morphologic similarity to sarcoma, MLL is also called "pseudosarcoma". MLL can degenerate into angiosarcoma without surgery. We present a case of MLL of the mons pubis in a 54-year-old man with a BMI of 48.6. PMID- 25123803 TI - [Treatment of pregnancy-associated breast cancer]. AB - CASE REPORT: A 25-year-old primipara, in the thirty-second week of her pregnancy observed a nodule in the upper outer quadrant of her left breast during self examination. Complex breast examination revealed calcification with 4 cm of diameter. Ductal malignant cells (C5) were identified by fine-needle aspiration biopsy, while core biopsy verified invasive ductal carcinoma, grade III (B5b). No manifestations of metastases were presented. After pregnancy termination wide excision with additional axillary sentinel lymph node biopsy was performed. Because of its positivity block dissection of axillary lymph nodes was carried out. The surgical therapy was followed by adjuvant chemo-, radio- and hormonal therapy. Later an angiomyxoma appeared in the right inguinal region, which was excised in toto. DISCUSSION: The incidence of pregnancy related malignant diseases is increasing, of which breast cancer predominates. Breast cancer, which is diagnosed during pregnancy or within the first year of delivery is called pregnancy-associated breast cancer. Because of the physiological changes in pregnancy the recognition of the disease is difficult. Therapy is complex, as besides the treatment of the mother, the safety of the fetus should be emphasized. The treatment strategies are different in the three trimesters. The surgical treatment can be performed during the whole pregnancy. The use of radiotherapy is controversial, because of teratogenic effects, while chemotherapy is permitted in the second and third trimesters. Nearly three years after the operation, our patient does not have any symptoms, her son is healthy. PMID- 25123807 TI - Introduction: celebrating the international year of crystallography: introduction. PMID- 25123806 TI - Induced sputum eicosanoids during aspirin bronchial challenge of asthmatic patients with aspirin hypersensitivity. AB - BACKGROUND: Altered metabolism of eicosanoids is a characteristic finding in aspirin-exacerbated respiratory disease (AERD). Bronchial challenge with lysyl aspirin can be used as a confirmatory diagnostic test for this clinical condition. Induced sputum allows to measure mediators of asthmatic inflammation in bronchial secretions. OBJECTIVES: To investigate the influence of inhaled lysyl-aspirin on sputum supernatant concentration of eicosanoids during the bronchial challenge test. Subjects with asthma hypersensitive to nonsteroidal anti-inflammatory drugs were compared with aspirin-tolerant asthmatic controls. METHODS: Induced sputum was collected before and following bronchial challenge with lysyl-aspirin. Sputum differential cell count and sputum supernatant concentrations of selected lipoxygenases products: 5-,12-,15 hydroxyeicosatetraenoic acid, cysteinyl leukotrienes, leukotriene B4 , 11-dehydro thromboxane B2 , and prostaglandins E2 , D2 , and F2alpha and their metabolites, were measured using validated methods of chromatography-mass spectrometry. RESULTS: Aspirin precipitated bronchoconstriction in all AERD subjects, but in none of the aspirin-tolerant asthmatics. Phenotypes of asthma based on the sputum cytology did not differ between the groups. Baseline sputum eosinophilia correlated with a higher leukotriene D4 (LTD4 ) and leukotriene E4 (LTE4 ) concentrations. LTC4 , PGE2 , and 11-dehydro-TXB2 did not differ between the groups, but levels of LTD4 , LTE4 , and PGD2 were significantly higher in AERD group. Following the challenge, LTD4 and LTE4 increased, while PGE2 and LTB4 decreased in AERD subjects only. CONCLUSIONS: During the bronchial challenge, decrease in PGE2 and its metabolite is accompanied by a surge in bronchoconstrictory cysteinyl leukotrienes produced at the expense of LTB4 in AERD subjects. Bronchial PGE2 inhibition in AERD seems specific and sensitive to a low dose of aspirin. PMID- 25123808 TI - Characterisation of a collection of Streptococcus pneumoniae isolates from patients suffering from acute exacerbations of chronic bronchitis: in vitro susceptibility to antibiotics and biofilm formation in relation to antibiotic efflux and serotypes/serogroups. AB - The correlation between Streptococcus pneumoniae serotypes, biofilm production, antibiotic susceptibility and drug efflux in isolates from patients suffering from acute exacerbations of chronic bronchitis (AECB) remains largely unexplored. Using 101 isolates collected from AECB patients for whom partial (n=51) or full (n=50) medical details were available, we determined serotypes (ST)/serogroups (SG) (Quellung reaction), antibiotic susceptibility patterns [MIC (microdilution) using EUCAST and CLSI criteria] and ability to produce biofilm in vitro (10-day model; crystal violet staining). The majority of patients were 55-75 years old and <5% were vaccinated against S. pneumoniae. Moreover, 54% showed high severity scores (GOLD 3-4), and comorbidities were frequent including hypertension (60%), cancer (24%) and diabetes (20%). Alcohol and/or tobacco dependence was >30%. Isolates of SG6-11-15-23, known for large biofilm production and causing chronic infections, were the most prevalent (>15% each), but other isolates also produced biofilm (SG9-18-22-27 and ST8-20 being most productive), except SG7, SG29 and ST5 (<2% of isolates each). Resistance (EUCAST breakpoints) was 8-13% for amoxicillin and cefuroxime, 35-39% for macrolides, 2-8% for fluoroquinolones and 2% for telithromycin. ST19A isolates showed resistance to all antibiotics, ST14 to all except moxifloxacin, and SG9 and SG19 to all except telithromycin, moxifloxacin and ceftriaxone (SG19 only). Solithromycin and telithromycin MICs were similar. No correlation was observed between biofilm production and MIC or efflux (macrolides, fluoroquinolones). S. pneumoniae serotyping may improve AECB treatment by avoiding antibiotics with predictable low activity, but it is not predictive of biofilm production. PMID- 25123809 TI - Emergence of Klebsiella pneumoniae co-producing NDM-1, OXA-48, CTX-M-15, CMY-16, QnrA and ArmA in Switzerland. AB - Extensively drug-resistant (XDR) Klebsiella pneumoniae isolates usually carry a single carbapenemase (e.g. KPC, NDM, OXA-48-like). Here we describe an XDR K. pneumoniae of sequence type 101 that was detected in the screening rectal swab of a patient transferred from the intensive care unit of a hospital located in Belgrade (Serbia) to Bern University Hospital (Switzerland). The isolate was resistant to all antibiotics with the exception of colistin [minimum inhibitory concentration] (MIC <= 0.125 MUg/mL), tigecycline (MIC = 0.5 MUg/mL) and fosfomycin (MIC = 2 MUg/mL). The isolate co-possessed class B (NDM-1) and class D (OXA-48) carbapenemases, class A extended-spectrum beta-lactamase (CTX-M-15), class C cephalosporinase (CMY-16), ArmA 16S rRNA methyltransferase, substitutions in GyrA and ParC, loss of OmpK35 porin, as well as other genes conferring resistance to quinolones (qnrA), tetracyclines [tet(A)], sulfonamides (sul1, sul2), trimethoprim (dfrA12, dfrA14), rifampicin (arr-1), chloramphenicol (cmlA1, floR) and streptomycin (aadA1). The patient was placed under contact isolation precautions preventing the spread of this nearly untreatable pathogen. PMID- 25123810 TI - Reversal of meticillin resistance in Staphylococcus aureus by the anthelmintic avermectin. PMID- 25123811 TI - Antifungal prophylaxis in lung transplantation. AB - Lung transplant (LTx) patients have an increased risk of developing invasive fungal infections (IFIs), particularly invasive aspergillosis. Rapid identification of the causative fungal pathogen, to allow for early administration of appropriate initial antifungal therapy, in LTx patients has been challenging due to the limited sensitivity and specificity of the diagnostic tools. Hence, there is increasing emphasis on antifungal prophylaxis in the LTx setting, given the high mortality rates and substantial cost of treating IFIs. Evidence for the optimal antifungal prophylactic approach in this setting, however, remains scant and inconsistent. This review will briefly discuss the epidemiology, risk factors, timing and clinical manifestations of fungal infections in LTx patients and will focus primarily on the available evidence related to the efficacy, safety and practicality of current prophylactic strategies in LTx recipients as well as challenges and gaps for future research. PMID- 25123812 TI - The relationships among dyspnoea, health-related quality of life and psychological factors in sarcoidosis. AB - BACKGROUND AND OBJECTIVES: Dyspnoea is a common symptom in sarcoidosis and is not predictably related to pulmonary function or radiology. A subjective symptom of dyspnoea is likely to be influenced by patient perception and experience. The aim of this study was to determine the prevalence and nature of dyspnoea in sarcoidosis and describe the relationship of dyspnoea to psychological factors and health-related quality of life (HRQL). METHODS: Fifty-six subjects (31 men, mean age 51 years) with sarcoidosis completed an HRQL measure, St George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS) and Nijmegen questionnaire. The presence of symptoms of dyspnoea was noted and qualitative descriptors for dyspnoea were chosen at peak exercise. Resting pulmonary function was performed. RESULTS: Sixty-four per cent of the subjects reported dyspnoea. Those with symptoms were older, had a longer duration of disease and with lower forced expiratory volume in 1 s (FEV1 ) and FEV1 /forced vital capacity (FVC) (all P < 0.05). Symptoms of dyspnoea were associated with worse HRQL (P < 0.005) and higher scores on the Nijmegen questionnaire (P < 0.05). Anxiety was not associated with dyspnoea and only a trend to greater depression was observed (P = 0.066). In multivariate analysis, SGRQ and Nijmegen scores predicted dyspnoea independent of demographic factors and resting pulmonary function. CONCLUSION: Dyspnoea is common in sarcoidosis and is associated with worse HRQL irrespective of baseline pulmonary function. Hyperventilation appears to be a factor contributing to dyspnoea and the Nijmegen questionnaire may be helpful in assessing dyspnoea and hyperventilation in sarcoidosis patients. PMID- 25123813 TI - Micropapillary urothelial carcinoma in a renal transplant recipient: a case report on urine cytomorphology emphasizing differentiation from high-grade urothelial carcinoma. PMID- 25123815 TI - An holistic approach to beach erosion vulnerability assessment. AB - Erosion is a major threat for coasts worldwide, beaches in particular, which constitute one of the most valuable coastal landforms. Vulnerability assessments related to beach erosion may contribute to planning measures to counteract erosion by identifying, quantifying and ranking vulnerability. Herein, we present a new index, the Beach Vulnerability Index (BVI), which combines simplicity in calculations, easily obtainable data and low processing capacity. This approach provides results not only for different beaches, but also for different sectors of the same beach and enables the identification of the relative significance of the processes involved. It functions through the numerical approximation of indicators that correspond to the mechanisms related to the processes that control beach evolution, such as sediment availability, wave climate, beach morhodynamics and sea level change. The BVI is also intended to be used as a managerial tool for beach sustainability, including resilience to climate change impact on beach erosion. PMID- 25123814 TI - High incidence of spontaneous cataracts in aging laboratory rabbits of an inbred strain. AB - OBJECTIVE: To investigate the occurrence of spontaneous cataracts in a breeding colony of the inbred EIII/JC strain of New Zealand White rabbits (Oryctolagus cuniculi) and the congenic strain of EIII/JC-HLA-A2.1transgenic rabbits. PROCEDURE: A retrospective study was conducted by collecting and analyzing data from clinical records for individual rabbits filed between January 2011 and October 2013. RESULTS: Thirteen cases (eight females and five males) of cataract were identified in a group of 51 EIII/JC inbred rabbits with a morbidity of 25.5%. The median age of the rabbits identified with unilateral or bilateral cataracts was 43 months in contrast to the median age of 23 months of the entire group of 51 rabbits. Additionally, seven cases (five females and two males) of cataracts were identified in a group of 21 EIII/JC-HLA-A2.1 transgenic rabbits. The EIII/JC-HLA-A2.1 transgenic rabbits showed similar morbidity (33.3%) and median age (41 months) for the development of cataracts as the EIII/JC rabbits. In both groups, none of the rabbits younger than 37 months developed cataracts while 13 (93%) of 14 EIII/JC rabbits aged 37-49 months and seven (63.6%) of 11 EIII/JC-HLA-A2.1 transgenic rabbits aged 37-43 months developed cataracts. In contrast, none of 78 outbred rabbits with a median age of 26 months (10-67 months) developed cataracts. CONCLUSION: Results of this study indicate that the occurrence and high incidence of spontaneous cataracts in this inbred strain (EIII/JC) of rabbits were strictly age related and consistently transmitted through inbreeding. PMID- 25123816 TI - Lipase-mediated lipid removal from propolis extract and its antiradical and antimicrobial activity. AB - BACKGROUND: Propolis contains many antioxidants such as polyphenols and flavonoids. However, propolis-derived lipid components interrupt an efficient isolation of antioxidants from propolis extract. We examined the effectiveness of various lipase treatments for the removal of lipids from propolis extract and evaluated the biological features of the extract. RESULTS: Lipase OF and Novozyme 435 treatments did not reduce fatty acid level in propolis extract. However, Lipozyme TL IM-treated propolis extract showed a significant decrease in fatty acid level, suggesting the removal of lipids. Lipozyme RM IM also significantly decreased the fatty acid level of the extract, but was accompanied by the reduction of polyphenols and flavonoids, which are antioxidants. In Lipozyme TL IM treatment, an increase in active flavonoids, such as Artepillin C and kaempferide, was observed, with a slight increase of ferric reducing/antioxidant power (FRAP) radical-scavenging activity. In addition, antimicrobial activity towards skin health-related bacteria such as Staphylococcus epidermidis and Propionibacterium acnes was enhanced by Lipozyme TL IM treatment. CONCLUSION: Lipozyme TL IM treatment effectively removes lipids from propolis extract and enhances antibacterial activity. Therefore, we suggest that Lipozyme TL IM is a useful lipase for lipid removal of propolis extract. PMID- 25123817 TI - Continuation and effectiveness of tadalafil once daily during a 6-month observational study in erectile dysfunction: the EDATE study. AB - AIMS: This was the first observational study evaluating treatment continuation, effectiveness and tolerability of tadalafil 5 mg once daily (TAD-OaD) in patients who chose and paid for treatment of erectile dysfunction (ED) in routine clinical practice. METHODS: Men >= 18 years with ED, treated previously with phosphodiesterase type 5 (PDE5)-inhibitor on-demand (PRN) or treatment-naive, were enrolled at 59 sites. For patients prescribed TAD-OaD at baseline (T1), change in erectile function (IIEF-EF and GAQ) was documented after 1-3 (T2) and 4 6 (T3) months. The primary outcome was the probability to switch/discontinue from TAD-OaD, estimated by Kaplan-Meier (KM) product-limit method. Changes in IIEF-EF were evaluated using a mixed model for repeated measures adjusting for patient baseline characteristics. RESULTS: Of 975 men enrolled (median age 56.8 years, 33.7% with previous PDE5-inhibitor use), 778 were prescribed TAD-OaD, 135 TAD-PRN and 62 sildenafil or vardenafil PRN. During the 6-month longitudinal observation, 107 patients (13.8% of 778) switched or discontinued TAD-OaD-treatment. KM-rates (95%CI) for continuing TAD-OaD at 2, 4 and 6 months were 94.0% (92.3, 95.7), 88.3% (85.9, 90.6) and 86.3% (83.7, 88.9), respectively. The 25th percentile of time to switch/discontinuation of TAD-OaD was estimated as 31.1 weeks (lower 95%CI 30.3 weeks). At T3, IIEF-EF scores had increased by 7.1 (LSmean; 95%CI 5.8, 8.5) points; 91.3% of patients reported improved erections. The most frequently reported AE was headache (10 patients; 1.3%); no new/unexpected safety signals were observed. CONCLUSION: Under routine conditions, and when patients were involved in treatment decision-making, more than 86% of men starting/switching to tadalafil once daily (OaD) at baseline continued tadalafil OaD treatment for >= 6 months. PMID- 25123818 TI - TRAIL expression levels in human hepatocellular carcinoma have implications for tumor growth, recurrence and survival. AB - The proapoptotic molecule TNF-related apoptosis-inducing ligand (TRAIL) has earned attention because of its ability to induce apoptosis in liver cancer cells without damaging normal liver cells. It may play an important role in preventing the development and outgrowth of hepatocellular carcinoma (HCC). TRAIL expression was investigated in a large series of human HCCs. We analyzed liver tissue from 108 patients undergoing partial liver resection (PLR) or liver transplantation (LT) because of either HCC or other indications. TRAIL expression was correlated with the cause of liver disease, demographic and clinical variables and pathologic properties. Our analysis found that in 66% of HCCs TRAIL expression was significantly lower than in the surrounding non-cancerous liver tissue (p<=0.012). Separation by cause of disease showed that HCC TRAIL mRNA expression was lower in almost all groups than in non-cancerous tissue but most significantly lower in NASH-associated liver tumors. Interestingly, low HCC TRAIL expression was found to correlate with tumor size (p<=0.007) and stage, as well as with tumor recurrence after resection and poor survival rates. The results of this study suggest that low TRAIL mRNA levels may be both a dominant feature in HCC development and growth and a predictor of tumor recurrence and poorer survival rates. PMID- 25123820 TI - Comparison of in vivo and in vitro properties of capsulated and noncapsulated variants of Mycoplasma mycoides subsp. mycoides strain Afade: a potential new insight into the biology of contagious bovine pleuropneumonia. AB - Mycoplasma mycoides subsp. mycoides (Mmm) strain Afade had previously been shown to undergo spontaneous phase variations between an opaque capsulated variant and a translucent (TR) variant devoid of a capsule but able to secrete cell-free exopolysaccharides. This phase variation is associated with an ON/OFF genetic switch in a glucose permease gene. In this study, in vivo and in vitro assays were conducted to compare the virulence of the two variants and their abilities to resist host defence. Capsulated variants were shown, in a mouse model, to induce longer bacteraemia that was correlated with better serum resistance in vitro. In contrast, TR variants displayed better ability to adhere to an inert support, linked to the absence of a capsule, changes in cell surface hydrophobicity and increased resistance to antimicrobial peptide and hydrogen peroxide. The switch from one variant population to another, which was observed both in vivo and in vitro under stress conditions, is further discussed as a means for Mmm to modulate its interactions with animal hosts during different stages of the disease. PMID- 25123821 TI - N8 (-) polynitrogen stabilized on multi-wall carbon nanotubes for oxygen reduction reactions at ambient conditions. AB - Polynitrogen (PN) species (Nn , n from 3 to 8) as highly energetic materials have attracted many theoretical calculations and predictions. N3 , N4 , N5 or their ions were experimentally detected under high-pressure and high-temperature conditions. Herein, a N8 (-) PN stabilized on the positively charged sidewalls of multi-walled carbon nanotubes (MWNTs) has been synthesized using cyclic voltammetry (CV) under ambient conditions. ATR-FTIR and Raman spectroscopic data assigned on the basis of density functional theory (DFT) calculations support the successful synthesis of a C2h symmetry chain structure of the N8 anion stabilized as MWNT(+) N8 (-) . Temperature programmed desorption (TPD) data show that MWNT(+) N8 (-) is thermally stable up to 400 degrees C. Oxygen-reduction reaction (ORR) experiments carried out using MWNT(+) N8 (-) as the cathodic catalyst shows that it is very active for ORR with an even higher current density than that of a commercial Pt/carbon catalyst. PMID- 25123822 TI - A randomized comparative trial of two decision tools for pregnant women with prior cesareans. AB - OBJECTIVE: Evaluate tools to help pregnant women with prior cesareans make informed decisions about having trials of labor. DESIGN: Randomized comparative trial. SETTING: A research assistant with a laptop met the women in quiet locations at clinics and at health fairs. PARTICIPANTS: Pregnant women (N = 131) who had one prior cesarean and were eligible for vaginal birth after cesarean (VBAC) participated one time between 2005 and 2007. METHODS: Women were randomized to receive either an evidence-based, interactive decision aid or two evidence-based educational brochures about cesarean delivery and VBAC. Effect on the decision-making process was assessed before and after the interventions. RESULTS: Compared to baseline, women in both groups felt more informed (F = 23.8, p < .001), were more clear about their birth priorities (F = 9.7, p = .002), felt more supported (F = 9.8, p = .002, and overall reported less conflict (F = 18.1, p < 0.001) after receiving either intervention. Women in their third trimesters reported greater clarity around birth priorities after using the interactive decision aid than women given brochures (F = 9.8, p = .003). CONCLUSION: Although both decision tools significantly reduced conflict around the birth decision compared to baseline, more work is needed to understand which format, the interactive decision aid or paper brochures, are more effective early and late in pregnancy. PMID- 25123819 TI - Can we unlock the potential of IGF-1R inhibition in cancer therapy? AB - IGF-1R inhibitors arrived in the clinic accompanied by optimism based on preclinical activity of IGF-1R targeting, and recognition that low IGF bioactivity protects from cancer. This was tempered by concerns about toxicity to normal tissue IGF-1R and cross-reactivity with insulin receptor (InsR). In fact, toxicity is not a show-stopper; the key issue is efficacy. While IGF-1R inhibition induces responses as monotherapy in sarcomas and with chemotherapy or targeted agents in common cancers, negative Phase 2/3 trials in unselected patients prompted the cessation of several Pharma programs. Here, we review completed and on-going trials of IGF-1R antibodies, kinase inhibitors and ligand antibodies. We assess candidate biomarkers for patient selection, highlighting the potential predictive value of circulating IGFs/IGFBPs, the need for standardized assays for IGF-1R, and preclinical evidence that variant InsRs mediate resistance to IGF-1R antibodies. We review hypothesis-led and unbiased approaches to evaluate IGF-1R inhibitors with other agents, and stress the need to consider sequencing with chemotherapy. The last few years were a tough time for IGF-1R therapeutics, but also brought progress in understanding IGF biology. Even failed studies include patients who derived benefit; they should be investigated to identify features distinguishing the tumors and host environment of responders from non-responders. We emphasize the importance of incorporating biospecimen collection into trial design, and wording patient consents to allow post hoc analysis of trial material as new data become available. Such information represents the key to unlocking the potential of this approach, to inform the next generation of trials of IGF signalling inhibitors. PMID- 25123823 TI - Costs of care for persons with opioid dependence in commercial integrated health systems. AB - BACKGROUND: When used in general medical practices, buprenorphine is an effective treatment for opioid dependence, yet little is known about how use of buprenorphine affects the utilization and cost of health care in commercial health systems. METHODS: The objective of this retrospective cohort study was to examine how buprenorphine affects patterns of medical care, addiction medicine services, and costs from the health system perspective. Individuals with two or more opioid-dependence diagnoses per year, in two large health systems (System A: n = 1836; System B: n = 4204) over the time span 2007-2008 were included. Propensity scores were used to help adjust for group differences. RESULTS: Patients receiving buprenorphine plus addiction counseling had significantly lower total health care costs than patients with little or no addiction treatment (mean health care costs with buprenorphine treatment = $13,578; vs. mean health care costs with no addiction treatment = $31,055; p < .0001), while those receiving buprenorphine plus addiction counseling and those with addiction counseling only did not differ significantly in total health care costs (mean costs with counseling only: $17,017; p = .5897). In comparison to patients receiving buprenorphine plus counseling, those with little or no addiction treatment had significantly greater use of primary care (p < .001), other medical visits (p = .001), and emergency services (p = .020). Patients with counseling only (compared to patients with buprenorphine plus counseling) used less inpatient detoxification (p < .001), and had significantly more PC visits (p = .001), other medical visits (p = .005), and mental health visits (p = .002). CONCLUSIONS: Buprenorphine is a viable alternative to other treatment approaches for opioid dependence in commercial integrated health systems, with total costs of health care similar to abstinence-based counseling. Patients with buprenorphine plus counseling had reduced use of general medical services compared to the alternatives. PMID- 25123825 TI - Haemolytic anaemia associated with Theileria sp. in an orphaned platypus. AB - CASE REPORT: The clinical and laboratory findings in an orphaned juvenile female platypus (Ornithorhynchus anatinus) that presented with a severe anaemia and tick infestation are reported. The animal developed a terminal septicaemia and died. Antemortem clinical pathology, postmortem histopathology and 18S rDNA sequencing supported a diagnosis of extravascular haemolytic anaemia secondary to Theileria ornithorhynchi infection. CONCLUSION: Although T. ornithorhynchi infection is common in the platypus, this is the first case in which it has been shown to cause a haemolytic anaemia in this species and molecular characterisation of the organism has been described. A review of the previous literature concerning T. ornithorhynchi and possible treatment options for future cases are discussed. PMID- 25123824 TI - TLR4-dependent activation of dendritic cells by an HMGB1-derived peptide adjuvant. AB - High mobility group box protein 1 (HMGB1) acts as an endogenous danger molecule that is released from necrotic cells and activated macrophages. We have previously shown that peptide Hp91, whose sequence corresponds to an area within the B-Box domain of HMGB1, activates dendritic cells (DCs) and acts as an adjuvant in vivo. Here we investigated the underlying mechanisms of Hp91-mediated DC activation. Hp91-induced secretion of IL-6 was dependent on clathrin- and dynamin-driven endocytosis of Hp91 and mediated through a MyD88- and TLR4 dependent pathway involving p38 MAPK and NFkappaB. Endosomal TLR4 has been shown to activate the MyD88-independent interferon pathway. Hp91-induced activation of pIRF3 and IL-6 secretion was reduced in IFNalphabetaR knockout DCs, suggesting an amplification loop via the IFNalphabetaR. These findings elucidate the mechanisms by which Hp91 acts as immunostimulatory peptide and may serve as a guide for the future development of synthetic Th1-type peptide adjuvants for vaccines. PMID- 25123826 TI - Performance of central venous catheterization by medical students: a retrospective study of students' logbooks. AB - BACKGROUND: Medical students often learn the skills necessary to perform a central venous catheterization in the operating room after simulator training. We examined the performance of central venous catheterization by medical students from the logbooks during their rotation in department of anesthesiology. METHODS: From the logbooks of medical students rotating in our department between January 2011 and June 2012, we obtained the kind and the number of central venous catheterization students had done, the results of the procedures whether they were success or failed, the reasons of the failures, complications, and the student self-reported confidence and satisfaction of their performance. RESULTS: There were 93 medical students performed 875 central venous catheterizations with landmark guidance on patients in the operating theater, and the mean number of catheterizations performed per student was 9.4 +/- 2.0, with a success rate of 67.3%. Adjusted for age, sex, body mass index, surgical category, ASA score and insertion site, the odds of successful catherization improved with cumulative practice (odds ratio 1.10 per additional central venous catheterization performed; 95% confidence interval 1.05-1.15). The major challenge students encountered during the procedure was the difficulty of finding the central veins, which led to 185 catheterizations failed. The complication rate of central venous catheterization by the students was 7.8%, while the most common complication was puncture of artery. The satisfaction and confidence of students regarding their performance increased with each additional procedure and decreased significantly if failure or complications had occurred. CONCLUSION: A student logbook is a useful tool for recording the actual procedural performance of students. From the logbooks, we could see the students' performance, challenges, satisfaction and confidence of central venous catheterization were improved through cumulative clinical practice of the procedure. PMID- 25123829 TI - Isolated hepatic tuberculosis mimicking liver tumors in a dialysis patient. AB - Cases of isolated hepatic tuberculosis (TB) are rare. The diagnosis is often delayed or missed because of nonspecific symptoms and laboratory findings. Besides, the disease is extremely rare even in a country where TB is an alarming public health problem. This report demonstrates the difficulty in correctly diagnosing local hepatic TB. We report the case of a 62-year-old male patient with end-stage renal disease treated with hemodialysis, who developed 2 months of abdominal distension and general anorexia, with hyperechoic hepatic lesions on ultrasound. Computed tomography suspected multiple liver tumors. The liver biopsy finally led to the diagnosis of TB of the liver without other involvements. We conclude that isolated hepatic TB is one of the rare forms of extrapulmonary TB in dialysis patients. A greater awareness of this rare clinical entity may prevent needless surgical interventions. PMID- 25123827 TI - Surface tailoring of nanoparticles via mixed-charge monolayers and their biomedical applications. AB - The recent convergence of nanomaterials and medicine has provided an expanding horizon for people to achieve encouraging advances in many biomedical applications such as cancer diagnosis and therapy. However, to realize desirable functions in the rather complex biological systems, a suitable surface coating is greatly in need for nanoparticles (NPs), regardless of the species. In this review, a recently developed surface modification strategy is highlighted--mixed charge monolayers--with an emphasis on the nanointerfaces of inorganic NPs. Two typical mixed-charge gold NPs (AuNPs) prepared from surface modifications with different combinations of oppositely charged alkanethiols are shown as detailed examples to discuss how the mixed-charge monolayer can help NPs meet the criteria for in vitro and in vivo biomedical applications, including those critical issues like colloidal stability, nonfouling properties, and smart responses (pH sensitivity) for tumor targeting. PMID- 25123828 TI - [Scaphoid surgery]. AB - Fracture of the scaphoid is the second most common fracture of the wrist. It requires a precise diagnosis and an individual therapy tailored to the patient. Computed tomography has assumed the central role in diagnostics and is obligatory to perform both verification and planning of treatment. Stable fractures can be treated conservatively while unstable fractures should be surgically stabilized. For this procedure different countersink compression screws are available. The fracture of the proximal pole must be considered separately because it is associated a very high rate of nonunion. No and incorrect treatment of fresh scaphoid fractures are the most common reasons for developing scaphoid nonunion. Depending on the location and perfusion, different surgical procedures including transplantation of avascular or vascularized bone grafts can be performed for treatment of scaphoid nonunion. PMID- 25123830 TI - Analytic power and sample size calculation for the genotypic transmission/disequilibrium test in case-parent trio studies. AB - Case-parent trio studies considering genotype data from children affected by a disease and their parents are frequently used to detect single nucleotide polymorphisms (SNPs) associated with disease. The most popular statistical tests for this study design are transmission/disequilibrium tests (TDTs). Several types of these tests have been developed, for example, procedures based on alleles or genotypes. Therefore, it is of great interest to examine which of these tests have the highest statistical power to detect SNPs associated with disease. Comparisons of the allelic and the genotypic TDT for individual SNPs have so far been conducted based on simulation studies, since the test statistic of the genotypic TDT was determined numerically. Recently, however, it has been shown that this test statistic can be presented in closed form. In this article, we employ this analytic solution to derive equations for calculating the statistical power and the required sample size for different types of the genotypic TDT. The power of this test is then compared with the one of the corresponding score test assuming the same mode of inheritance as well as the allelic TDT based on a multiplicative mode of inheritance, which is equivalent to the score test assuming an additive mode of inheritance. This is, thus, the first time the power of these tests are compared based on equations, yielding instant results and omitting the need for time-consuming simulation studies. This comparison reveals that these tests have almost the same power, with the score test being slightly more powerful. PMID- 25123831 TI - Neuroendocrine mechanisms for immune system regulation during stress in fish. AB - In the last years, the aquaculture crops have experienced an explosive and intensive growth, because of the high demand for protein. This growth has increased fish susceptibility to diseases and subsequent death. The constant biotic and abiotic changes experienced by fish species in culture are challenges that induce physiological, endocrine and immunological responses. These changes mitigate stress effects at the cellular level to maintain homeostasis. The effects of stress on the immune system have been studied for many years. While acute stress can have beneficial effects, chronic stress inhibits the immune response in mammals and teleost fish. In response to stress, a signaling cascade is triggered by the activation of neural circuits in the central nervous system because the hypothalamus is the central modulator of stress. This leads to the production of catecholamines, corticosteroid-releasing hormone, adrenocorticotropic hormone and glucocorticoids, which are the essential neuroendocrine mediators for this activation. Because stress situations are energetically demanding, the neuroendocrine signals are involved in metabolic support and will suppress the "less important" immune function. Understanding the cellular mechanisms of the neuroendocrine regulation of immunity in fish will allow the development of new pharmaceutical strategies and therapeutics for the prevention and treatment of diseases triggered by stress at all stages of fish cultures for commercial production. PMID- 25123832 TI - Gender-specific metabolic responses in hepatopancreas of mussel Mytilus galloprovincialis challenged by Vibrio harveyi. AB - Mussel Mytilus galloprovincialis is a marine aquaculture shellfish and frequently studied in shellfish immunology. In this work, the gender-specific metabolic responses induced by Vibrio harveyi in hepatopancreas from M. galloprovincialis were characterized using NMR-based metabolomics. In details, V. harveyi challenge increased the levels of amino acids including (valine, leucine, isoleucine, threonine, alanine, arginine and tyrosine) and ATP, and decreased the level of glucose in male mussel hepatopancreas. In V. harveyi-challenged female mussel hepatopancreas, both threonine and AMP were significantly elevated, and choline, phoshphocholine, sn-glycero-3-phosphocholine, taurine, betaine and ATP were depleted. Obviously, only threonine was similarly altered to that in V. harveyi challenged male mussel hepatopancreas. These findings confirmed the gender specific metabolic responses in mussels challenged by V. harveyi. Overall, V. harveyi induced an enhanced energy demand through activated glycolysis and immune response indicated by increased BCAAs in male mussel hepatopancreas. In female mussel hepatopancreas, V. harveyi basically caused disturbances in both osmotic regulation and energy metabolism through the metabolic pathways of conversions of phosphocholine and ADP to choline and ATP, and sn-glycero-3-phosphocholine and H2O into choline and sn-glycerol 3-phosphate. The altered mRNA expression levels of related genes (Cu/Zn-SOD, HSP90, lysozyme and defensin) suggested that V. harveyi induced obvious oxidative and immune stresses in both male and female mussel hepatopancreas. This work demonstrated that V. harveyi could induce gender specific metabolic responses in mussel M. galloprovincialis hepatopancreas using NMR-based metabolomics. PMID- 25123835 TI - The National Institutes of Health Physician-Scientist Workforce Working Group report: a roadmap for preserving the physician-scientist. PMID- 25123833 TI - Cloning and expression analysis of three novel CC chemokine genes from Japanese flounder (Paralichthys olivaceus). AB - Chemokines are small cytokines secreted by various cell types. They not only function in cell activation, differentiation and trafficking, but they also have influences on many biological processes. In this study, three novel CC chemokine genes Paol-SCYA105, 106 and 107 in Japanese flounder (Paralichthys olivaceus) were cloned and characterized. Paol-SCYA105 was mainly detected in gill, kidney and spleen, Paol-SCYA106 was detected in all tissues examined and Paol-SCYA107 was mainly detected in the spleen and kidney. Paol-SCYA105 and Paol-SCYA106 gene expressions peaked in kidney at day 3 after viral hemorrhagic septicemia virus infection and decreased at day 6, but Paol-SCYA106 still remained at a high level at day 6. Paol-SCYA107 gene expression was significantly up-regulated in kidney at day 6 after viral hemorrhagic septicemia virus infection. In response to infection by Gram-negative Edwardsiella tarda and Gram-positive Streptococcus iniae in kidney, only Paol-SCYA106 gene expression significantly increased. Together, these results indicate that these three novel CC chemokines are involved in the immune response against pathogen infections. PMID- 25123838 TI - The correlation of contrast-enhanced ultrasound and MRI perfusion quantitative analysis in rabbit VX2 liver cancer. AB - Our objective is to explore the value of liver cancer contrast-enhanced ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the correlation between these two analysis methods. Rabbit VX2 liver cancer model was established in this study. CEUS was applied. Sono Vue was applied in rabbits by ear vein to dynamically observe and record the blood perfusion and changes in the process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative analysis was used to analyze the mean enhancement time and change law of maximal slope increasing, which were further compared with the pathological examination results. Quantitative indicators of liver cancer CEUS and MRI perfusion quantitative analysis were compared, and the correlation between them was analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer showed "fast in, fast out" model while MRI perfusion quantitative analysis showed that quantitative parameter MTE of tumor tissue increased and MSI decreased: the difference was statistically significant (P < 0.01). The diagnostic results of CEUS and MRI perfusion quantitative analysis were not significantly different (P > 0.05). However, the quantitative parameter of them were significantly positively correlated (P < 0.05). CEUS and MRI perfusion quantitative analysis can both dynamically monitor the liver cancer lesion and surrounding liver parenchyma, and the quantitative parameters of them are correlated. The combined application of both is of importance in early diagnosis of liver cancer. PMID- 25123837 TI - Y-chromosome analysis in a Northwest Iberian population: unraveling the impact of Northern African lineages. AB - OBJECTIVES: To provide new clues about the genetic origin, composition and structure of the population of the Spanish province of Zamora, with an emphasis on the genetic impact of the period of Islamic rule in the Iberian Peninsula. METHODS: Polymorphisms in the paternally inherited Y-chromosome, Single Nucleotide Polymorphisms and Short Tandem Repeats, were analyzed in 235 unrelated males born in six different regions in the Zamora province. RESULTS: A relatively homogenous Y-chromosome haplogroup composition was observed in the Zamora province. Haplogroups R1b1-P25 and I-M170, widespread in European populations, accounted for 64.9% of the total sample. Moreover, all of the observed African lineages, accounting for 10.2% of the total variability, belonged to haplogroups having Northwest African origin (E1b1b1b-M81, E1b1b1a-beta-M78, and J1-M267). CONCLUSIONS: No differences between regions or sub-structure due to geographical boundaries were detected. The specific Northwest African male lineages observed contrast with the mitochondrial DNA data, where the majority of African lineages were found to be sub-Saharan. This work made it possible to study the impact of recent historical events in the male gene pool in the province of Zamora in Spain. PMID- 25123839 TI - Effects of tirofiban on platelet activation and endothelial function in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. AB - This pilot study examined, for the first time, the effect of intracoronary administration of tirofiban, an inhibitor of platelet aggregation, on platelet activation and endothelial dysfunction in patients with ST-segment-elevated myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). A total of 119 STEMI patients were randomized into either tirofiban group (n = 72, intracoronary injection of 10 MUg/kg tirofiban prior to PCI, followed by intravenous infusion at 0.15 MUg/kg min) or a control group (n = 47), which did not receive tirofiban. Periprocedural administration of tirofiban was associated with significantly reduced levels of platelet activation (lower levels of CD62P and PAC-1) and endothelial dysfunction (reduced levels of endothelial microparticles, VCAM-1, and ICAM-1) 48 h after PCI. At 10 days after PCI, patients in the tirofiban group had a higher incidence of complete STR (78.7 vs. 65.0%) and higher left ventricular ejection fractions (47.8 vs. 44.2) compared to those in the control group. The clinical outcomes between two groups did not differ significantly two weeks after treatment. The results demonstrated that periprocedural administration of tirofiban is associated with significantly attenuated platelet activation and endothelial dysfunction in STEMI patients undergoing PCI. This may have contributed to the improved myocardial reperfusion and preservation of left ventricular systolic function in these patients. PMID- 25123841 TI - Unraveling cell populations in tumors by single-cell mass cytometry. AB - The development of new biotechnologies for the analysis of individual cells in heterogeneous populations is an important direction of life science research. This review provides a critical overview of relevant and recent advances in the field of single-cell mass cytometry, focusing on the latest applications in the study of cell heterogeneity. New approaches for multiparameter single-cell imaging, alongside advanced computational tools for deep mining of high dimensional mass cytometric data, are facilitating the visualization of specific cell types and their interactions in complex cellular assemblies, such as tumors, potentially revealing new insights into cancer biology. PMID- 25123840 TI - Analysis of volatile organic compounds liberated and metabolised by human umbilical vein endothelial cells (HUVEC) in vitro. AB - Gas chromatography with mass spectrometric detection combined with head-space needle trap extraction as the pre-concentration technique was applied to identify and quantify volatile organic compounds released or metabolised by human umbilical vein endothelial cells. Amongst the consumed species there were eight aldehydes (2-methyl 2-propenal, 2-methyl propanal, 2-methyl butanal, 3-methyl butanal, n-hexanal, benzaldehyde, n-octanal and n-nonanal) and n-butyl acetate. Further eight compounds (ethyl acetate, ethyl propanoate, ethyl butyrate, 3 heptanone, 2-octanone, 2-nonanone, 2-methyl-5-(methylthio)-furan and toluene) were found to be emitted by the cells under study. Possible metabolic pathways leading to the uptake and release of these compounds by HUVEC are proposed and discussed. The uptake of aldehydes by endothelial cells questions the reliability of species from this chemical class as breath or blood markers of disease processes in human organism. The analysis of volatiles released or emitted by cell lines is shown to have a potential for the identification and assessment of enzymes activities and expression. PMID- 25123842 TI - Adaptive finite-time stabilization for a class of uncertain high order nonholonomic systems. AB - In this paper, the adaptive finite-time stabilization problem is investigated for a class of high order nonholonomic systems in power chained form with strong nonlinear drifts and nonlinear parameterization. By skillfully using finite-time stability theorem, parameter separation technique and adding a power integrator method, an adaptive state feedback controller is obtained. To overcome the obstacle that x-subsystem is uncontrollable when the control input u0=0, a novel switching control strategy is given. Based on this, the designed controller renders that the states of closed-loop system are regulated to zero in a finite time. Two illustrative examples are also provided to demonstrate the effectiveness of the proposed controller. PMID- 25123844 TI - Neurodevelopmental delays and macrocephaly in 17p13.1 microduplication syndrome. AB - Microduplication of chromosome 17p13.1 is a rarely reported chromosome abnormality associated with neurodevelopmental delays. We describe two unrelated patients with overlapping microduplications of chromosome 17p13.1. The first patient is a 2-year-old male who presented with neurodevelopmental delays and macrocephaly. He was found to have a de novo 788 kb copy gain of 17p13.2p13.1 and a de novo 134 kb copy gain of 17p13.1. These duplications include multiple candidate genes, including EFNB3, NLGN2, DLG4, GABARAP, and DULLARD, which may be responsible for neurodevelopmental delays in affected individuals. The second patient is a 29-year-old female with mild intellectual disability and relative macrocephaly. She was found to have a 62.5 kb copy gain of chromosome 17p13.1 that includes the DLG4, GABARAP, and DULLARD genes. The DLG4, GABARAP, and DULLARD genes included in the microduplications of both our patients appear to be candidate genes for neurodevelopmental delays and macrocephaly in individuals with 17p13.1 microduplication syndrome. PMID- 25123843 TI - Hypoalbuminaemia is associated with mortality in patients undergoing cytoreductive nephrectomy. AB - OBJECTIVE: To evaluate whether poor nutrition is associated with mortality in patients undergoing cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: A multi-institutional review of prospective databases identified 246 patients meeting inclusion criteria who underwent CN for mRCC from 1993 to 2012. Nutritional markers evaluated were: body mass index <18.5 kg/m(2) , serum albumin <3.5 g/dL, or preoperative weight loss of >=5% of body weight. Primary outcomes were overall (OS) and disease-specific survival (DSS). Secondary outcome was 'early mortality' defined as death at <=6 months of surgery. Survival curves were estimated using the Kaplan-Meier product limit method and multivariate analysis using logistic regression was used to test associations between nutritional markers and survival outcomes. RESULTS: In all, 119 patients (median follow-up 17 months) were categorised as having any abnormal nutrition parameter (48%). Hypoalbuminaemia was the only independent predictor of OS and DSS (OS: median 8 vs 23 months, P < 0.001; DSS: 11 vs 33 months, P < 0.001). On multivariate analysis, hypoalbuminaemia remained a significant predictor of death for both overall [hazard ratio (HR) 2, 95% confidence interval (CI) 1.4-2.8; P < 0.001) and disease-specific mortality (HR 2.2, 95% CI 1.4-3.3; P < 0.001). Hypoalbuminaemia was also associated with early mortality (overall: P < 0.001 and disease specific: P = 0.002). CONCLUSION: Patients with mRCC and hypoalbuminaemia undergoing CN have decreased OS and CSS, and increased risk of all-cause and disease-specific early mortality. As such, serum albumin may help risk stratify patients selected as candidates for CN. Furthermore, future work should evaluate whether nutritional depletion is a modifiable risk factor. PMID- 25123845 TI - Penta-O-galloyl-beta-D-glucose suppresses EGF-induced eIF3i expression through inhibition of the PI3K/AKT/mTOR pathway in prostate cancer cells. AB - Approximately 70% of prostate cancer patients will develop bone metastasis in axial and other regions of the skeleton. Epidermal growth factor (EGF) generated from bone tissue contributes to prostate cancer metastasis. In a previous study, penta-O-galloyl-beta-D-glucose (PGG) suppressed androgen-independent prostate cancer bone metastasis by transcriptionally repressing EGF-induced MMP-9 expression. This study utilized proteomics to analyze the effects of PGG in EGF induced prostate cancer bone metastasis. This study showed that PGG suppressed EGF-induced eIF3i expression in PC-3 cells. By transfection of eIF3i shRNA, it was observed that reduced eIF3i expression suppressed the invasion of PC-3 cells in vitro. PGG reduced EGF-induced eIF3i expression through inhibition of the PI3K/AKT/mTOR pathway. Therefore, PGG may be able to be used as a potential new therapeutic drug for prostate cancer bone metastasis. PMID- 25123847 TI - Volatility of serum creatinine relative to tacrolimus levels predicts kidney transplant rejection. AB - BACKGROUND: We hypothesized that greater volatility of creatinine (SCr) relative to tacrolimus levels [Tac] (VCT) is associated with an increased risk of rejection. MATERIAL AND METHODS: Retrospective chart review was performed of all single-kidney-only transplants in our Renal Transplant Program from March 2004 to March 2010 (n=117) whose immunosuppressive regimen included tacrolimus (n=81). We collected all available SCr and [Tac] over the first 2 years post-transplant and calculated the VCT for each patient. SCr and [Tac] values were excluded from the first month and from the rise that occurred immediately preceding a rejection episode. RESULTS: Univariate analysis revealed that VCT was associated with increased odds of biopsy-proven rejection. A logistic regression model including donor type and HLA matches revealed that VCT (OR=1.16 [1.07, 1.26], p=0.0004) was strongly associated with rejection. ROC curve analysis yielded an AUC=0.823 (p<0.0001). CONCLUSIONS: Increased volatility of SCr relative to [Tac] is associated with an increased risk of rejection. Whereas increased variation in [Tac] levels has been shown to indicate reduced adherence, increased VCT may signal 'immunologic unrest' in the graft. Further studies are warranted to determine if intervention at the time when volatility increases can lower the risk of an acute rejection episode. PMID- 25123849 TI - Polypyrrole-derived nitrogen and oxygen co-doped mesoporous carbons as efficient metal-free electrocatalyst for hydrazine oxidation. AB - We demonstrate that polypyrrole-derived nitrogen and oxygen co-doped mesoporous carbons can serve as efficient, metal-free electrocatalysts for hydrazine oxidation reaction, with low overpotential and high current density. The materials' structures and the nature and type of their included dopants, which can be controlled by varying the synthetic conditions, can affect the electrocatalytic properties of the materials. PMID- 25123848 TI - [60]Fullerene derivative modulates adenosine and metabotropic glutamate receptors gene expression: a possible protective effect against hypoxia. AB - BACKGROUND: Glutamate, the main excitatory neurotransmitter, is involved in learning and memory processes but at higher concentration results excitotoxic causing degeneration and neuronal death. Adenosine is a nucleoside that exhibit neuroprotective effects by modulating of glutamate release. Hypoxic and related oxidative conditions, in which adenosine and metabotropic glutamate receptors are involved, have been demonstrated to contribute to neurodegenerative processes occurring in certain human pathologies. RESULTS: Human neuroblastoma cells (SH SY5Y) were used to evaluate the long time (24, 48 and 72 hours) effects of a [60]fullerene hydrosoluble derivative (t3ss) as potential inhibitor of hypoxic insult. Low oxygen concentration (5% O2) caused cell death, which was avoided by t3ss exposure in a concentration dependent manner. In addition, gene expression analysis by real time PCR of adenosine A1, A2A and A2B and metabotropic glutamate 1 and 5 receptors revealed that t3ss significantly increased A1 and mGlu1 expression in hypoxic conditions. Moreover, t3ss prevented the hypoxia-induced increase in A2A mRNA expression. CONCLUSIONS: As t3ss causes overexpression of adenosine A1 and metabotropic glutamate receptors which have been shown to be neuroprotective, our results point to a radical scavenger protective effect of t3ss through the enhancement of these neuroprotective receptors expression. Therefore, the utility of these nanoparticles as therapeutic target to avoid degeneration and cell death of neurodegenerative diseases is suggested. PMID- 25123850 TI - Up-regulated expression of Dicer reveals poor prognosis in laryngeal squamous cell carcinoma. AB - CONCLUSIONS: Increased expression of Dicer may be a prognostic biomarker for patients with laryngeal squamous cell carcinoma (LSCC). OBJECTIVES: Recent studies have shown that many microRNAs (miRNAs) play an important role in the development and progression of human cancers. Dicer, one of the most important enzymes of the miRNA machinery, performs the final step of biogenesis of miRNAs. This study aimed to investigate the impact of Dicer expression on patient survival in human LSCC. METHODS: We detected the expression of Dicer in larynx tissue specimens from 76 LSCC samples and 26 polyps by immunohistochemistry. The clinicopathological and prognostic significance of Dicer expression was investigated in LSCC. RESULTS: Our data showed that the expression of Dicer was significantly higher in the LSCC than in the polyp tissue specimens. Moreover, the expression level of Dicer was significantly associated with the pTNM stage and tumor lymph node metastasis. Kaplan-Meier survival analyses revealed a strong association between tumor Dicer expression and the survival of the patients with LSCC. PMID- 25123851 TI - Comparability of single measurements of serum testosterone to the 24-hour C(avg) in patients using testosterone 2% solution. AB - INTRODUCTION: Efficacy of testosterone replacement therapy is determined by the proportion of men with 24-hour average serum testosterone concentration (Cavg ) in the normal range. In clinical practice, monitoring and dose adjustments are based on single testosterone measurements; however, how single measurements reflect Cavg is unclear. AIM: This post-hoc analysis evaluated whether single serum testosterone measurements and Cavg from the same day are both in the normal range in men receiving testosterone replacement therapy. METHODS: In an open label, multicenter, titration trial, androgen-deficient men (N = 155) were started on 60-mg daily morning dose of testosterone 2% solution (Axiron(r), Eli Lilly and Company, Indianapolis, Indiana, USA) applied to axillae (30 mg/axilla). Serum testosterone Cavg was determined on Days 15, 60, and 120. If necessary, dose was adjusted to maintain Cavg in the normal range (300-1,050 ng/dL). This analysis included subjects (n = 105) whose Cavg was within the normal range on Days 15, 60, and 120. MAIN OUTCOME MEASURES: Proportion of men with normal serum testosterone levels at 2, 4, or 8 hours post-dose on Days 15, 60, and 120. RESULTS: Greater than 93% of subjects had testosterone serum levels within the normal range 2, 4, or 8 hours post-dose on at least 1 day. In subjects with blood samples available from Days 15 and 60 or Days 15 and 120, 71.1% to 79.8% had normal levels at 2, 4, or 8 hours post-dose on both days, and in subjects with blood samples available from Days 15, 60, and 120, 63.9% to 68.8% had normal levels at 2, 4, or 8 hours post-application on all 3 days. CONCLUSION: Less than 70% of single testosterone measurements made on 3 separate days were concordant with same-day Cavg for all 3 days. These findings, which are specific for testosterone 2% solution, indicate that single measurements do not always reflect the 24-hour Cavg , and may possibly lead to inappropriate dose adjustments. PMID- 25123852 TI - The pros and cons of funnel plots as an aid to risk communication and patient decision making. AB - Funnel plots, which simultaneously display a sample statistic and the corresponding sample size for multiple cases, have a range of applications. In medicine, they are used to display treatment outcome rates and caseload volume by institution, which can inform strategic decisions about health care delivery. We investigated lay people's understanding of such plots and explored their suitability as an aid to individual treatment decisions. In two studies, 172 participants answered objective questions about funnel plots representing the surgical outcomes (survival or mortality rates) of institutions varying in caseload, and indicated their preferred institutions. Accuracy for extracting objective information was high, unless question phrasing was inconsistent with the plot's survival/mortality framing, or participants had low numeracy levels. Participants integrated caseload-volume and outcome-rate data when forming preferences, but were influenced by reference lines on the plot to make inappropriate discriminations between institutions with similar outcome rates. With careful choice of accompanying language, funnel plots can be readily understood and are therefore a useful tool for communicating risk. However, they are less effective as a decision aid for individual patient's treatment decisions, and we recommend refinements to the standard presentation of the plots if they are to be used for that purpose. PMID- 25123853 TI - 'The thieving magpie'? No evidence for attraction to shiny objects. AB - It is widely accepted in European culture that magpies (Pica pica) are unconditionally attracted to shiny objects and routinely steal small trinkets such as jewellery, almost as a compulsion. Despite the long history of this folklore, published accounts of magpies collecting shiny objects are rare and empirical evidence for the behaviour is lacking. The latter is surprising considering that an attraction to bright objects is well documented in some bird species. The present study aims to clarify whether magpies show greater attraction to shiny objects than non-shiny objects when presented at the same time. We did not find evidence of an unconditional attraction to shiny objects in either captive or free-living birds. Instead, all objects elicited responses indicating neophobia in free-living birds. We suggest that humans notice when magpies occasionally pick up shiny objects because they believe the birds find them attractive, while it goes unnoticed when magpies interact with less eye catching items. The folklore may therefore result from observation bias and cultural inflation of orally transmitted episodic events. PMID- 25123854 TI - [Neglected infectious diseases in the tropics]. PMID- 25123846 TI - A systematic review of causes of sudden and severe headache (Thunderclap Headache): should lists be evidence based? AB - BACKGROUND: There are many potential causes of sudden and severe headache (thunderclap headache), the most important of which is aneurysmal subarachnoid haemorrhage. Published academic reviews report a wide range of causes. We sought to create a definitive list of causes, other than aneurysmal subarachnoid haemorrhage, using a systematic review. METHODS: Systematic Review of EMBASE and MEDLINE databases using pre-defined search criteria up to September 2009. We extracted data from any original research paper or case report describing a case of someone presenting with a sudden and severe headache, and summarized the published causes. RESULTS: Our search identified over 21,000 titles, of which 1224 articles were scrutinized in full. 213 articles described 2345 people with sudden and severe headache, and we identified 6 English language academic review articles. A total of 119 causes were identified, of which 46 (38%) were not mentioned in published academic review articles. Using capture-recapture analysis, we estimate that our search was 98% complete. There is only one population-based estimate of the incidence of sudden and severe headache at 43 cases per 100,000. In cohort studies, the most common causes identified were primary headaches or headaches of uncertain cause. Vasoconstriction syndromes are commonly mentioned in case reports or case series. The most common cause not mentioned in academic reviews was pneumocephalus. 70 non-English language articles were identified but these did not contain additional causes. CONCLUSIONS: There are over 100 different published causes of sudden and severe headache, other than aneurysmal subarachnoid haemorrhage. We have now made a definitive list of causes for future reference which we intend to maintain. There is a need for an up to date population based description of cause of sudden and severe headache as the modern epidemiology of thunderclap headache may require updating in the light of research on cerebral vasoconstriction syndromes. PMID- 25123855 TI - [Leptospirosis seroprevalence and associated features in rice farmers of tropical region of Peru]. AB - OBJECTIVES: To estimate the seroprevalence of leptospirosis in rice farmers of the Alto Mayo Valley in the Peruvian region of San Martin and to identify factors associated with infection. MATERIALS AND METHODS: A cross-sectional study was conducted between October and November of 2010 on a sample of 254 farmers from eleven irrigation committees in the Alto Mayo Valley. A blood sample was collected as well as sociodemographic, household and labor characteristics in the form of a questionnaire. The presence of antibodies against leptospira was determined using the microscopic agglutination test and the IgM ELISA. RESULTS: The seroprevalence by agglutination was 64.6% (95% CI: 58.6-70.6). The IgM ELISA test was reactive in 15,0% (95% CI: 10.5-19.5). The most frequent serovar were Icterohaemorrhagiae, Autumnalis, Australis, Panama and Grippotyphosa. Independently associated factors were handling rodents (adjusted OR (aOR): 7.9; 95% CI: 1.6-37.9), working barefoot (aOR: 2.9; 95% CI: 1.2-6.8) and male sex (aOR: 4.5; 95% CI: 1.3-15.3). CONCLUSIONS: The Alto Mayo Valley is a hyperendemic for leptospirosis. The most important factors were associated with working barefoot and handling rodents in crop fields. Consequently, it is recommended to implement interventions that affect these two factors in order to reduce the risk of infection in rice farmers. PMID- 25123856 TI - [Prevalence of hepatitis B infection in children under 5 years old on indigenous communities of the Peruvian Amazonia after immunization interventions]. AB - OBJECTIVES: To determine the prevalence of hepatitis B virus (HVB) infection and seroprotection in indigenous children living in three draining basins of the Peruvian Amazon. MATERIALS AND METHODS: A cross sectional study was conducted in three draining basins (Pastaza, Morona and Lower Urubamba rivers), home to six indigenous populations: shapra, candoshi, machiguenga, yine, ashaninka and nanti. Children under 5 years were included. A survey and review of the vaccination card was applied, and a serum sample was processed with ELISA for HBsAg, total anti HBc and anti-HBs was obtained, defining "seroprotected children" if they were reactive to anti-HBs and non-reactive to anti-HBc. RESULTS: A total of 742 children under 5 years old residents in six indigenous communities were included in the study. 380 (51.2%) were male and 169 (22.9%) one year old or younger. Regarding recorded HVB vaccination on the card, only 434 (58.5%) had received three doses; 208 (38.8%) received the first dose within 24 hours. No cases were detected with HBsAg. 88.8% of children had seroconverted, varying between 67-100% across the populations. CONCLUSIONS: No cases of chronic HBV infection were detected. The vaccination coverage by card revision is low, contrasting with high seroconversion rates. PMID- 25123857 TI - [Gestational syphilis and associated factors in public hospitals of Peru during 2000-2010]. AB - OBJECTIVES: To determine the epidemiological profile of gestational syphilis and associated factors in a Peruvian population. MATERIALS AND METHODS: The study is a secondary analysis of data obtained from public hospitals in Peru for the 2000 2010 period. 652,636 pregnant women were included from 37 cities and 45 health centers in Peru. RESULTS: The prevalence of gestational syphilis was 0.7%, while 80.7% reported screening for gestational syphilis. The highest prevalence of maternal syphilis is found in the lowland rainforest followed by the highland rainforest. In the three regions of Peru decreased prevalence of gestational syphilis has been seen throughout the years. The prevalence for 2010 are 0.2% on the coast, in the highlands 0.23% and 0.47% in the jungle. The lack of education and prenatal care, high parity, cohabiting or single, and living in the jungle, are associated with having a positive syphilis test. CONCLUSIONS: The results suggests that prevalence of gestational syphilis has declined over the decade 2000-2010. PMID- 25123858 TI - [Comparing two protocols of DNA extraction of Trypanosoma cruzi cultured in axenic medium]. AB - OBJECTIVES: To compare two extraction protocols of Trypanosoma cruzi DNA for use in DNA amplification of kinetoplast minicircles (kDNA) through the technique of Polymerase Chain Reaction (PCR). MATERIALS AND METHODS: Epimastigotes of T. cruzi were cultured in axenic conditions and masses from 1.5 to 100 x 106 parasites were obtained. DNA extraction was performed using two protocols: extraction with organic solvents (phenol/chloroform), and with resin (Chelex100), from different parasitic sediments. Concentration and purity of DNA was determined by spectrophotometry, and integrity was assessed by agarose gel electrophoresis. Analysis of variance and comparisons of means were performed through Tukey's test, using the Statistix 8.0 software. RESULTS: Ten DNA extractions were done of each one of the different amounts of parasitic sediments. In the DNA extraction with Chelex100 resin, a higher performance was obtained but a lower purity and integrity compared to the extraction with organic solvents. However, it allowed a product amplification of 330 bp of T. cruzi kDNA. CONCLUSIONS: Although the technique of Chelex100 provided less purity and integrity of DNA, it allowed a successful amplification of kDNA by PCR, avoiding the use of laborious techniques and toxic organic solvents. PMID- 25123859 TI - [Neonatal mortality, analysis of surveillance registers, and neonatal medical histories of 2011 in Huanuco and Ucayali, Peru]. AB - OBJECTIVES: To estimate the rate of neonatal mortality and to describe neonatal deaths in 2011 in hospitals of the Ministry of Health at Huanuco and Ucayali (Peru). MATERIALS AND METHODS: Cross-sectional study from September to November 2012 in Huanuco and Ucayali. Records of neonatal deaths in 2011 were reviewed from provincial municipalities, regional health directorates and four referral hospitals. To calculate mortality rates, we used the most reliable information sources by region. Reviewing 185 medical records in hospitals allowed us to describe the root causes of neonatal deaths. RESULTS: In 2011, 10,886 live births and 158 neonatal deaths were reported in Huanuco, with a rate of 14.5 deaths per 1000 live births. In Ucayali, 11,441 live births and 138 neonatal deaths were reported, with a rate of 12.1 deaths per 1000 live births. Most hospital neonatal deaths occurred in the first 7 days of life (87%), in preterm infants (73.9%) and with low birth weight (67%). The most common underlying causes of neonatal deaths were infection (31.4%), congenital malformation (22.2%) and prematurity (18.9%). CONCLUSIONS: Neonatal mortality rate in the studied regions was higher than the national average. The results suggest the need for effective and comprehensive interventions during pregnancy, childbirth and the early postnatal period; this last period is the most vulnerable in the neonate. PMID- 25123860 TI - [Prevalence and demographic factors associated with ferritin deficiency in Colombian children, 2010]. AB - OBJECTIVES: To determine prevalence and socio-demographic factors associated with ferritin deficiency in a representative sample of children in Colombia. MATERIALS AND METHODS: Cross sectional secondary data analysis of the National Survey on the Nutritional Situation (ENSIN) conducted in 2010 in Colombia in 3542 children between 12 and 59 months. Plasma ferritin levels were determined by chemiluminescence and values <12 ug/L were considered as deficit ferritin. Sociodemographic factors (sex, age, ethnicity, socioeconomic status, and geographical region) were collected using a structured questionnaire. All analyses were performed taking into account the complex nature of the sample. RESULTS: It was found that the average value of ferritin was 32.1 g/L, (CI 95%: 30.7-35.6).10.6% (CI 95%: 9.3-12.0) of the children had ferritin levels less than 12.0 ug/L. The multivariate logistic regression shows that children aged 12 to 23 (OR 5.1, CI 95%: 3.3-8.0) and 24 to 35 months (OR 2.4, CI 95%: 1.5-3.7), belonging to the indigenous ethnic group (OR 1.8, CI 95%: 1.1-2.8), living in the Atlantic region (OR 2.0, CI 95%: 1.1 -3.6), or Pacific area (OR 2.0, CI 95%: 1.1 3.6) were associated with a higher probability of ferritin deficiencies. CONCLUSIONS: A significant prevalence of anemia caused by ferritin deficiency was found as well as various sociodemographic factors that contributed to the likelihood of increasing this problem. Comprehensive interventions are recommended in which nutritional and educational components are involved. PMID- 25123861 TI - [Evaluating maternal child care practices in extreme poverty areas in Peru, 2012]. AB - OBJECTIVES: To evaluate maternal and child care practices in areas with extreme poverty in Peru. MATERIALS AND METHODS: Cross-sectional study conducted between August and September 2012; with probabilistic, three-stage stratification by "department" (geographic region) sampling. 540 households were selected that had at least one child younger than 36 months (475 households) and/or a pregnant women (80 households), in rural areas of Cajamarca, Amazonas, Huanuco, Ayacucho, Huancavelica, Apurimac, Cusco, Puno and Ucayali. RESULTS: Regarding the last pregnancy, 69.0% of the mothers reported having had their first prenatal care in the first trimester; 65.3% reported having completed more than six check-ups throughout the pregnancy; 81.1% reported having given birth in a health facility, and only 31.0% chose a method of family planning within 42 days postpartum. With regard to the last child under 3 years old, 64.1% had early mother-infant contact, and 62.8% initiated breastfeeding within one hour of birth. In addition, 89.6% of children under 6 months old exclusively received breastfeeding and 89.1% of children aged 6-8 months old already had received complementary feeding. Fever, diarrhea, vomiting and breathing difficulty were the most mentioned warning signs for seeking care for children. CONCLUSIONS: Through this study, a baseline has been established on which a strategy can be designed and implemented to improve best practices for maternal and child care as part of the "Programa de Apoyo" within the Health Sector Reform. PMID- 25123862 TI - [Study of correlation between diagnostic hypertriglyceridemic waist and metabolic syndrome in adults in Trujillo, Peru]. AB - OBJECTIVES: To determine the correlation between hypertriglyceridemic waist (HTGW) and metabolic syndrome (MS) in adults of Trujillo according to diagnostic criteria. MATERIALS AND METHODS: Observational, prospective and cross-sectional study with a sample of 500 adults in Trujillo, selected by probability sampling and stratified by sex and age. Information on anthropometric measurements, blood pressure and biochemical tests was collected; Criteria proposed by the ATP III and Joint Interim Statement (JIS) for MS, as well as Gomez and JIS for HTGW were applied. EPIDAT software was used to calculate Z test, Student t test and the Kappa (k) with a confidence interval (CI) of 95%. RESULTS: Information regarding 239 men and 261 women were collected. The frequency of HTGW according to Gomez criteria was 30% in the total sample, 29.7% in men and 30.3% women. According to JIS criteria the frequency was 34% in the total sample, 38.1% in men and 30.3% women. Metabolic Syndrome with JIS criteria had good agreement with HTGW according to Gomez criteria with k = 0.63 and according to JIS criteria with k = 0.66. CONCLUSIONS: Good agreement was evidenced between the HTGW according to Gomez and JIS criteria and MS according to JIS. PMID- 25123863 TI - [Effect of extracts of Geranium ayavacense W. (Pasuchaca) on glycemia on rats with experimental diabetes mellitus]. AB - OBJECTIVES: To determine if the lyophilized aqueous extract of Geranium ayavacense (Pasuchaca) has any effect on glycemia in rats with experimental diabetes mellitus. MATERIALS AND METHODS: Experimental diabetes was induced with alloxan. Rats included in the study met the following criteria: glycemia greater than 200 mg/dL post administration of alloxan, and with a weight greater than 200 g. Rats with experimental diabetes were divided into six groups of eight rats each. Group I received 3 mL of distilled water (control); group II received Geranium ayavacense 12.7 mg/kg; group III received Geranium ayavacense 100 mg/kg; group IV received Geranium ayavacense 200 mg/kg; group V received Geranium ayavacense 300 mg/kg; group VI received Geranium ayavacense 500 mg/kg. Basal glycemia was determined. Glycemia evaluations were performed at the 1st, 3rd, 6th, 12th and 24th hour after administrating the different interventions. RESULTS: Geranium ayavacense groups of 300 and 500 mg/kg decreased glycemia significantly (p <0.01) in every hour assessed after administration of the extract, when compared with the control group. Geranium ayavacense group of 300 mg/kg decreased their blood glucose 8.14; 10.68; 14.87; 19.36 and 23.7% in the 1st, 3rd, 6th, 12th and 24th hour respectively. CONCLUSIONS: Under experimental conditions, the aqueous extract of Geranium ayavacense has hypoglycemic effects in rats. PMID- 25123864 TI - [Epidemiological profile of traffic-related disability in Peru, 2012]. AB - OBJECTIVES: To describe the epidemiological profile of people living with disabilities due to traffic accidents (TA) in Peru. MATERIALS AND METHODS: Secondary analysis of the National Survey Specialized on Disability (ENEDIS) of 2012 and an ecological analysis of TA records of the Ministry of Transportation and Communications was done. RESULTS: Disability by traffic accidents (DAT) was reported by 49,036 persons; 81.3% of whom live in urban areas. The most frequent disability was limited locomotion and skill (77.4%), followed by visual impairment (22.9%). Dependence for activities was reported in 44.7% of persons with disabilities. The regions with the highest prevalence of TA have a higher prevalence of disability by traffic accidents (Spearman coefficient: 0.426, p=0.034). CONCLUSIONS: Most of disability due to TA is found in urban areas, correspond to males and consist of persons in economically productive age. The most common form of disability is in locomotion. Most of individuals do not receive any form of rehabilitation, which accentuates health inequity related to traffic accidents. PMID- 25123865 TI - [Bartonella henselae in children with regional adenitis treated in a Peruvian national hospital, 2012]. AB - In order to determine the frequency of seropositive cases of Bartonella henselae in children with regional adenitis treated in a national hospital in Peru, a cross-sectional study was conducted in 106 children with regional adenitis greater than 1 cm in diameter. The sample was selected from patients aged 5-11 years seen at the National Institute of Child Health for acute onset of regional adentitis, with more than five days of symptoms. B. henselae seropositivity was defined by indirect immunofluorescence test. We found that 86 children (81.1%) were positive for B.henselae. The median age of the patients was 7 years. In the bivariate analysis, the following associated factors were found: aged 5 years, history of fever, lymphadenopathy greater than 4 cm and reported contact with cat. In conclusion, children with regional adenitis treated in this national referral hospital showed a high frequency of positive serology for B. henselae. PMID- 25123866 TI - [Specificity of the intradermal Montenegro test in patients infected by Trypanosoma cruzi from different regions of Peru]. AB - In order to assess the specificity of the leishmanin skin test in Chagas disease patients without clinical history of leishmaniasis, present or former. A sample of 102 persons infected with Trypanosoma cruzi (14 acute cases with parasitological diagnosis and 88 chronic cases) through the demonstration of IgG antibodies by ELISA and indirect immunofluorescence (IIF) were evaluated with leishmanin soluble antigen which contained Leishmania (Viannia) peruviana concentration of 25-30 ug/mL. Only five people showed cutaneous hypersensitivity reaction to the application of the antigen between hours 48 and 72. The Leishmanin skin test evaluated was negative in 97 people infected with T. cruzi, thus specificity of 95.1% was achieved. In conclusion, the intradermal Montenegro test is a simple and effective diagnostic tool that also could be used to discriminate infections by Leishmania or T. cruzi, in Peruvian geographic areas where both parasites are present. PMID- 25123867 TI - [Mutant alleles associated to chloroquine and sulfadoxine-pyrimethanime resistance in Plasmodium falciparum of the Ecuador-Peru and Ecuador-Colombia borders]. AB - The frequency of mutations in pfCRT and DHFR/DHPS genes of Plasmodium falciparum associated with resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated in 83 strains from the districts of Esmeralda and Machala, located on the borders of Ecuador-Peru and Ecuador-Colombia in 2002. Polymerase chain reaction (PCR), conventional and its variants, was used. Mutations in the pfCRT gene were found in more than 90% of the samples from Esmeralda and Machala. For the DHFR gene, 90% of the strains were mutant samples from Esmeralda, 3 were double mutations and 1 was a triple mutation. In Machala, 25% were simple mutant forms and 75% mixed mutant forms (wild forms/mutant). In conclusion, resistance to chloroquine has been fixed in strains carrying K76T pfCRT mutation, whereas genetic imprinting for resistance to pyrimethamine is evolving, particularly in the district of Esmeralda. PMID- 25123868 TI - [Purification of antigenic fraction 27-28 kDa from the metabolic antigen from metabolic secreted-excreted from Fasciola hepatica]. AB - Antigenic fractions of 27-28 kDa from Fasciola hepatica were purified by size exclusion chromatography for use in the diagnosis of human fasciolosis. Excretion and secretion antigens were obtained from living adult flukes collected from sheep and cattle liver, and cultured in minimum essential medium. The reactivity of the purified antigen and efficacy were assessed by immunoblot test using four sera with human fascioliasis; four sera with other parasites, and two negative sera. We conclude that the purified antigenic fractions do not cross-react with other parasites by immunoblot. Therefore, purified proteins are considered as potential candidates to be used for the diagnosis of human fascioliasis. PMID- 25123869 TI - [Publication of research projects for certification as medical specialists at a Peruvian university, 2007-2010]. AB - In order to determine the frequency of publication in a scientific journal of the research projects done for medical specialty certification, a search was conducted in Google Scholar, Pubmed, biomedical databases and Peruvian medical society journals. These publications were research projects carried out by medical residents graduated from the Faculty of Medicine at the Universidad Peruana Cayetano Heredia, to obtain the certification of medical specialist. Of 351 medical residents graduated between the years 2007-2010, 199 (65.5%) completed their research project and 47 (23.6%) published it in a scientific journal. The "medicine" (non-surgical) specialty area had the highest frequency of publications. All publications were in Spanish journals, the majority in indexed journals in regional databases. We conclude that 23.6% of the research projects for certification as medical specialists are published, most often in low visibility journals. PMID- 25123870 TI - [Assessment of dot blot tests and latex agglutination for cysticercosis diagnostic in Peru]. AB - In order to evaluate dot blot tests and latex agglutination for the detection of human cysticercosis with liquid antigen of Taenia solium cysticerci, 125 human sera were used, of which 60 were from people with cysticercosis confirmed by Western Blot, 45 with other parasitic diseases and 20 apparently healthy. The optimal concentration of antigen to impregnate dot blot strips was 0.01 ug/uL, and to impregnate the latex particles was 0.092 ug/uL. For the dot blot test, a sensitivity of 100% and specificity of 87.7% was found. For latex agglutination, a sensitivity of 93.3% and specificity of 89.2% was found. Both tests may be useful and feasible to implement alternatives of serological diagnosis in laboratories in endemic areas of Peru. PMID- 25123871 TI - [Hematophagous bats as reservoirs of rabies]. AB - Rabies continues to be a challenge for public health authorities and a constraint to the livestock industry in Latin America. Wild and domestic canines and vampire bats are the main transmitter species and reservoirs of the disease. Currently, variations observed in the epidemiological profile of rabies, where the species of hematophagous bat Desmodus rotundus constitutes the main transmitting species. Over the years, knowledge has accumulated about the ecology, biology and behavior of this species and the natural history of rabies, which should lead to continuous development of methods of population control of d. Rotundus as well as prevention and diagnostic tools for rabies. Ecological relationships of this species with other hematophagous and non-hematophagous bats is unknown, and there is much room for improvement in reporting systems and surveillance, as well as creating greater awareness among the farming community. Understanding the impact of human-induced environmental changes on the rabies virus in bats should be cause for further investigation. This will require a combination of field studies with mathematical models and new diagnostic tools. This review aims to present the most relevant issues on the role of hematophagous bats as reservoirs and transmitters of the rabies virus. PMID- 25123872 TI - [Historical review of the distribution of Anopheles (Nyssorhynchus) darlingi (Diptera: Culicidae) in the Peruvian Amazon]. AB - Anopheles (Nyssorhynchus) darlingi has been reported since 1931 in border areas of the department of Loreto, mainly along the borders with Brazil and Colombia. In 1994, during an outbreak of malaria, An. darlingi was found in neighboring towns to Iquitos. At present, its distribution has expanded considerably in Loreto. This paper reviews literature available for all possible information on the distribution of mosquitoes, particularly anopheline in the Amazon region of the country, with special emphasis on An darlingi. Entomological collections were also conducted in the departments of Madre de Dios and Ucayali in order to know and verify the distribution of An. darlingi. At present, the distribution of the species is confined to localities in southeastern Peru with Bolivia border towns, in a town near the Abujao River in the department of Ucayali, and widely in the northeastern region of the Amazon basin of Loreto in Peru. PMID- 25123873 TI - [The road to elimination: an overview of neglected infectious diseases in Latin America and the Caribbean]. AB - Neglected infectious diseases (NID) affect mainly isolated populations living in isolation and in poor socioeconomic conditions. These diseases, by their chronic and silent nature, often affect communities with a weak political voice. This translates into very little attention or political priority; which is reflected in minimal and insufficient preventive measures, monitoring and control. However, there is evidence this situation is changing favorably in some countries of the Americas. In recent years, several resolutions (official agreement of the member countries of the Pan American Health Organization / World Health Organization PAHO / WHO), regional and global agreements on public health; with a greater commitment from the pharmaceutical industry, and other donors and international partners in combination with the development and use of integrated action plans have allowed countries to intensify public interventions to control these diseases and thus achieve target elimination of NID. Onchocerciasis, lymphatic filariasis, Chagas disease, leprosy and trachoma blindness, among others, have been eliminated in several countries and endemic areas, regardless of the level of development of the country or geographical area where they are located. The political decision reflected in adequate financial resources in the next decade will be crucial to achieving the goals of elimination of NID (regional and national). PMID- 25123874 TI - [Neglected infectious diseases: an ongoing challenge for public health and equity in Peru]. AB - Neglected Infectious Diseases (NID) affect more than one billion people worldwide, and are associated with poverty, geographic isolation of populations, social stigma, lack of precise data on estimates on both the global and local burden of disease (underreporting of the diseases), inadequate financial and political resources to effective control measures, lack of lobbying on behalf of the most vulnerable population, as well as scarce drug and diagnostic methods development. In this article we describe the relationship between NID, poverty and inequality, we propose a new concept of disease in the tropics, expanding the list of diseases that share characteristics with NID in the Peruvian context, discuss the limited availability of drugs and diagnostic tests to properly deal with these diseases, as well as highlight the contributions by the Peruvian National Institute of Health, and as final thoughts, we state that the solution for the prevention and control of NID must include an integrated approach, including the social determinants of health in the context of the fight against poverty and inequality. PMID- 25123875 TI - [Critical appraisal about control programs and elimination of leprosy in Peru, and its consequences for Peru and America]. AB - A critical analysis of health control measures that historically took place in Peru to the present which has led Peru to officially consider leprosy as an "eliminated" public health problem. We will also discuss the validity of the status given the neglect of health surveillance, disbanded specialized control entities, health medical staff forgetting to account for leprosy in early stages, the presence of undiagnosed smear-positive leprosy in Lima and the undeniable hidden prevalence, suggest that there is a danger to the country and the region that a re-emergence of leprosy will occur, if relevant and appropriate sanitary measures are not taken. PMID- 25123876 TI - [Urbanization of Chagas disease in Peru: experiences in prevention and control]. AB - In Peru, Chagas disease has an epidemiological significance in three macro regions, one of them is the southern macro-region formed by the departments of Arequipa, Moquegua and Tacna. In 1965 a successful control was performed by house spraying insecticides, however, the persistence of the vector made it necessary for a second control plan that was implemented in 2000 and followed the guidelines of CONAL Plan, based on the elimination of Triatoma infestans and screening in blood banks.This plan was successful in Tacna and Moquegua, therefore these departments were considered free of vectorial transmission by the Pan American Health Organization. A ssimilar situation has not been achieved in the department of Arequipa because of the presence, among other factors, of rural migration to the city, in this way the urbanization of Chagas disease is a new epidemiological scenario of which we need to know more. PMID- 25123877 TI - [Experiences in the prevention and control of Carrion's disease in Peru]. AB - Carrion's disease, the iconic disease in Peruvian medicine has been found in the mountains of Ecuador, Colombia and the Andean valleys of Peru. In the 1990s, the phenomenon of El Nino was associated with significantly increased risk of disease in Ancash, Cajamarca and Cusco. In Cusco in 1998 there was an acute phase epidemic in various Andean provinces and the jungle area. Between 2001 and 2005 the disease has spread or reactivated in different regions such as Ancash, Cajamarca, Amazonas, Piura, Cusco, La Libertad, Puno, and Ayacucho. In 2004 a major outbreak of the disease in all of Peru was presented, reporting more than 11 164 cases, and therefore diverse strategies based vector susceptibility studies was applied, lowering significantly the number of cases. PMID- 25123878 TI - [Sporotrichosis and paracoccidioidomycosis in Peru: experiences in prevention and control]. AB - The epidemiological picture of sporotrichosis and paracoccidioidomycosis in Peru and Latin America is sporadic, fragmented, and geographically limited, mainly due to lack of mandatory reporting and limited diagnostic coverage. However, research contributions related to understanding the interaction of these fungi, the response of the host and the environment, the use of spatial analysis that relates the distribution of these mycoses, population density and climate, contributes to the design of prevention and control strategies of these mycosis and suggest epidemiological risk maps management, based on the habitat of the fungus. This information will be used by doctors, tourists and people living in rural areas where mycoses are endemic. The aim of the paper is to present a review of the topic through research findings that contribute to the prevention and control of these mycosis. PMID- 25123880 TI - [Creutzfeldt-Jakob disease in Peru: report of eleven cases]. AB - Creutzfeldt-Jakob disease (CJD) is a fatal neurological disease caused by pathological isoform of the human prion protein. Clinical features of six cases of the sporadic form of CJD with definitive diagnosis by histopathology, and five cases with probable diagnosis were reported in patients treated at the Peruvian National Institute of Neurological Sciences. The average age of onset in definite cases was 55.8 years and in probable cases was 59.6, mostly males. The average disease duration was 8.8 months. A typical EEG was found in 50% of definite cases and in 80% of probable. The 14-3-3 protein in cerebrospinal fluid was positive in a probable case, and typical MRI findings were observed in two probable cases. All cases studied had a typical clinical course of the disease, and it is considered as the first report of CJD in Peru. PMID- 25123881 TI - [Disseminated cysticercosis: report of a case in Peru]. AB - Cysticercosis is a neglected and endemic disease in Peru that commonly affects the central nervous system (CNS), causing neurocysticercosis (NCC). However, only a few reports of disseminated cysticercosis (DCC) exist in the world. In this article we present a case report of a male, 82 year old patient from the department of Junin (Peru). He presented a sudden loss of consciousness associated with generalized tonic-clonic seizures. CT scan and brain MRI showed multiple cystic lesions with scolex presence inside and compatible with massive NCC. Thoracic, abdominal and pelvic MRI showed multi-organ dissemination of cysticerci. Although there is little therapeutic experience in cases of DCC, the patient received deworming treatment with albendazole and corticoids, in this way a favorable clinical outcome was achieved without complications during hospitalization. PMID- 25123879 TI - [Unifying criteria for late neonatal sepsis: proposal for an algorithm of diagnostic surveillance]. AB - Infections are a major cause of death in neonates. Diagnosis of neonatal sepsis is a major challenge because newborns have very nonspecific clinical signs and auxiliary tests have low sensitivity. In order to improve the correct diagnosis of this condition, we propose an algorithm of diagnostic surveillance for late neonatal sepsis in Peru and countries of the region. The algorithm classifies the episodes as confirmed, probable or possible sepsis, and especially seeks to identify those episodes that do not correspond to sepsis, preventing other diseases to be qualified as "sepsis". Better diagnostics will enable more realistic rates of neonatal sepsis, improve the use of antibiotics and avoid their negative effects on newborns, as well as provide a more accurate view of their impact on public health. PMID- 25123882 TI - [Acute arterial occlusion associated disseminated hydatidosis]. AB - Hydatidosis or echinococcosis are terms used to denote the zoonotic infestation caused by adult and larval stages (metacestode) of the cestode from the genus Echinococcus (family tenidae). The term hydatidosis should be applied to the infestation caused by the metacestode while echinococcosis for the larval and adult stages. In Peru there is a high prevalence of this infection, liver and lung being the most affected organs. There are factors from the host and from the infectious agent that contribute to this infection, with the immune component of the host as an important infection and dissemination point. A case of acute arterial occlusion associated with disseminated hydatidosis in a 54 years old patient, born and from Huancavelica, with sudden onset of an acute arterial obstruction is reported. The patient did not improve after surgery and died within 48 hours of presentation. PMID- 25123883 TI - [Carrion's disease complicated with severe acute leptospirosis: a case report]. AB - The case of an adult, 56 year old male is reported, from Sihuas (Ancash) who presented at Hospital Nacional Dos de Mayo with fever, jaundice and anemia. In three days of hospitalization, he developed severe anemia (Hb: 11.8 to 6.7 g / dL) and generalized myalgias associated with a sudden worsening jaundice correlated with elevated bilirubin (TB 3.2 to 19.6 mg / dL direct dominance) and general deterioration. Microbiological smear and culture were positive for Bartonella bacilliformis. Subsequent serology (microagglutination) was positive for Lesptospira serovar Pomona. The patient was given specific antibiotic therapy (ceftriaxone and ciprofloxacin), transfused two units of packed red blood cells, improved clinically and was discharged. PMID- 25123884 TI - [Human bartonellosis: before and after Daniel Alcides Carrion]. AB - This is a review of bibliographic aspects associated to the knowledge about human bartonelosis before and after the death of Daniel Alcides Carrion. Emphasis is placed on stimulus in the development of medical research in Peru by the self inoculation and subsequent death of Carrion especially in relation to human bartonellosis, conducted by Peruvian researchers and others around the world. The review includes the basic area of knowledge about the bacteria that causes the illness, the host response to infection as well as the biphasic behavior of the disease. The revised bibliography includes contributions to the knowledge of the disease in the last 100 years, now known with the eponym "Carrion's disease". PMID- 25123885 TI - [Life cycle of Strongyloides fuelleborni: images and videos]. PMID- 25123886 TI - [Financing for rare or orphan diseases: a thing to do]. PMID- 25123887 TI - [Monge's disease: a forgotten eponym?]. PMID- 25123888 TI - [Epidemiological surveillance, molecular biology and dengue 5]. PMID- 25123889 TI - [Scientific production of members of the National Academy of Sciences]. PMID- 25123890 TI - [Tuberculosis and diabetes comorbidity in a hospital of Colombia]. PMID- 25123891 TI - [Environmental health in Peru]. PMID- 25123892 TI - [Analysis of complex survey in population data]. PMID- 25123893 TI - [Stroke in Peru: a forgotten and unattended prevalent disease]. PMID- 25123894 TI - Direct hydrogenation of biomass-derived butyric acid to n-butanol over a ruthenium-tin bimetallic catalyst. AB - Catalytic hydrogenation of organic carboxylic acids and their esters, for example, cellulosic ethanol from fermentation of acetic acid and hydrogenation of ethyl acetate is a promising possibility for future biorefinery concepts. A hybrid conversion process based on selective hydrogenation of butyric acid combined with fermentation of glucose has been developed for producing biobutanol. ZnO-supported Ru-Sn bimetallic catalysts exhibits unprecedentedly superior performance in the vapor-phase hydrogenation of biomass-derived butyric acid to n-butanol (>98% yield) for 3500 h without deactivation. PMID- 25123896 TI - Have the New GP Contract and NICE guidelines improved the clinical care of people with epilepsy? AB - PURPOSE: This retrospective audit was to assess the effect of the New General Practitioner (GP) Contract and National Institute for Health and Care Excellence (NICE) guidelines on the care and management of people with epilepsy (PWE) during the period of observation from April 2004 to April 2009. METHOD: The case notes of 540 people on anti-epilepsy drugs (AEDs) aged 16 years were reviewed in 13 general practices serving Ellesmere Port and Neston. RESULTS: Forty-nine percent of people with poorly controlled epilepsy were not under shared care. Diagnostic doubt existed in 25 (5%) people. There was no evidence that the original diagnosis had been actively reviewed by the GP in any case. There were 98 (18%) women of childbearing age, in 21 of whom there was no evidence of pre-conceptual counselling ever having taken place, and 61 (62%) were not receiving folic acid routinely. Thirty-nine (7%) people were demonstrably non-compliant, whilst 74 (14%) people had prescription anomalies consisting mainly of inappropriate multi dose regimens. CONCLUSION: Despite marked improvements in review rates after the introduction of the New GP Contract five years previously, there are still significant unmet needs in this patient group. Clinical Commissioning Groups (CCGs) should consider funding an intermediate tier of care incorporating GPs with a special interest in epilepsy (GPwSIes) and Epilepsy Nurse Specialists (ENS) for PWE to improve and maintain existing and future primary care, as epilepsy is phased out of the Quality and Outcomes Framework (QOF). PMID- 25123895 TI - Cloning and expression of A. oryzae beta-glucosidase in Pichia pastoris. AB - A beta-glucosidase gene (bgl) from Aspergillus oryzae GIF-10 was cloned, sequenced and expressed. Its full-length DNA sequence was 2,903 bp and included three introns. The full-length cDNA sequence contained an open reading frame of 2,586 nucleotides, encoding 862 amino acids with a potential secretion signal. The A. oryzae GIF-10 bgl was functionally expressed in Pichia pastoris. After 7 day induction, protein yield reached 321 mg/mL. Using salicin as the substrate, the specific activity of the purified enzyme reached 215 U/mg. The purified recombinant beta-glucosidase was a 110-kDa glycoprotein with optimum catalytic activity at pH 5.0 and 50 degrees C. The enzyme was stable between 20 and 60 degrees C, and retained 65% of its activity after being held at 60 degrees C for 30 min. The recombinant beta-glucosidase was relatively stable in a broad range of pHs, from 4.0 to 6.5. It showed broad specific activity, hydrolyzing a range of (1-4)-beta-diglycosides and (1-4)-alpha-diglycosides, and Mn(2+) stimulated its activity significantly. PMID- 25123897 TI - Can the syndrome of transient epileptic amnesia be the first feature of Alzheimer's disease? PMID- 25123898 TI - MindTheGap: integrated detection and assembly of short and long insertions. AB - MOTIVATION: Insertions play an important role in genome evolution. However, such variants are difficult to detect from short-read sequencing data, especially when they exceed the paired-end insert size. Many approaches have been proposed to call short insertion variants based on paired-end mapping. However, there remains a lack of practical methods to detect and assemble long variants. RESULTS: We propose here an original method, called MindTheGap, for the integrated detection and assembly of insertion variants from re-sequencing data. Importantly, it is designed to call insertions of any size, whether they are novel or duplicated, homozygous or heterozygous in the donor genome. MindTheGap uses an efficient k mer-based method to detect insertion sites in a reference genome, and subsequently assemble them from the donor reads. MindTheGap showed high recall and precision on simulated datasets of various genome complexities. When applied to real Caenorhabditis elegans and human NA12878 datasets, MindTheGap detected and correctly assembled insertions >1 kb, using at most 14 GB of memory. PMID- 25123899 TI - NetComm: a network analysis tool based on communicability. AB - MOTIVATION: Set-based network similarity metrics are increasingly used to productively analyze genome-wide data. Conventional approaches, such as mean shortest path and clique-based metrics, have been useful but are not well suited to all applications. Computational scientists in other disciplines have developed communicability as a complementary metric. Network communicability considers all paths of all lengths between two network members. Given the success of previous network analyses of protein-protein interactions, we applied the concepts of network communicability to this problem. Here we show that our communicability implementation has advantages over traditional approaches. Overall, analyses suggest network communicability has considerable utility in analysis of large scale biological networks. AVAILABILITY AND IMPLEMENTATION: We provide our method as an R package for use in both human protein-protein interaction network analyses and analyses of arbitrary networks along with a tutorial at http://www.shawlab.org/NetComm/. PMID- 25123900 TI - READemption-a tool for the computational analysis of deep-sequencing-based transcriptome data. AB - RNA-Seq has become a potent and widely used method to qualitatively and quantitatively study transcriptomes. To draw biological conclusions based on RNA Seq data, several steps, some of which are computationally intensive, have to be taken. Our READemption pipeline takes care of these individual tasks and integrates them into an easy-to-use tool with a command line interface. To leverage the full power of modern computers, most subcommands of READemption offer parallel data processing. While READemption was mainly developed for the analysis of bacterial primary transcriptomes, we have successfully applied it to analyze RNA-Seq reads from other sample types, including whole transcriptomes and RNA immunoprecipitated with proteins, not only from bacteria but also from eukaryotes and archaea. AVAILABILITY AND IMPLEMENTATION: READemption is implemented in Python and is published under the ISC open source license. The tool and documentation is hosted at http://pythonhosted.org/READemption (DOI:10.6084/m9.figshare.977849). PMID- 25123901 TI - gCUP: rapid GPU-based HIV-1 co-receptor usage prediction for next-generation sequencing. AB - SUMMARY: Next-generation sequencing (NGS) has a large potential in HIV diagnostics, and genotypic prediction models have been developed and successfully tested in the recent years. However, albeit being highly accurate, these computational models lack computational efficiency to reach their full potential. In this study, we demonstrate the use of graphics processing units (GPUs) in combination with a computational prediction model for HIV tropism. Our new model named gCUP, parallelized and optimized for GPU, is highly accurate and can classify >175 000 sequences per second on an NVIDIA GeForce GTX 460. The computational efficiency of our new model is the next step to enable NGS technologies to reach clinical significance in HIV diagnostics. Moreover, our approach is not limited to HIV tropism prediction, but can also be easily adapted to other settings, e.g. drug resistance prediction. AVAILABILITY AND IMPLEMENTATION: The source code can be downloaded at http://www.heiderlab.de CONTACT: d.heider@wz-straubing.de. PMID- 25123902 TI - Cross-validation under separate sampling: strong bias and how to correct it. AB - MOTIVATION: It is commonly assumed in pattern recognition that cross-validation error estimation is 'almost unbiased' as long as the number of folds is not too small. While this is true for random sampling, it is not true with separate sampling, where the populations are independently sampled, which is a common situation in bioinformatics. RESULTS: We demonstrate, via analytical and numerical methods, that classical cross-validation can have strong bias under separate sampling, depending on the difference between the sampling ratios and the true population probabilities. We propose a new separate-sampling cross validation error estimator, and prove that it satisfies an 'almost unbiased' theorem similar to that of random-sampling cross-validation. We present two case studies with previously published data, which show that the results can change drastically if the correct form of cross-validation is used. AVAILABILITY AND IMPLEMENTATION: The source code in C++, along with the Supplementary Materials, is available at: http://gsp.tamu.edu/Publications/supplementary/zollanvari13/. PMID- 25123903 TI - HapMuC: somatic mutation calling using heterozygous germ line variants near candidate mutations. AB - MOTIVATION: Identifying somatic changes from tumor and matched normal sequences has become a standard approach in cancer research. More specifically, this requires accurate detection of somatic point mutations with low allele frequencies in impure and heterogeneous cancer samples. Although haplotype phasing information derived by using heterozygous germ line variants near candidate mutations would improve accuracy, no somatic mutation caller that uses such information is currently available. RESULTS: We propose a Bayesian hierarchical method, termed HapMuC, in which power is increased by using available information on heterozygous germ line variants located near candidate mutations. We first constructed two generative models (the mutation model and the error model). In the generative models, we prepared candidate haplotypes, considering a heterozygous germ line variant if available, and the observed reads were realigned to the haplotypes. We then inferred the haplotype frequencies and computed the marginal likelihoods using a variational Bayesian algorithm. Finally, we derived a Bayes factor for evaluating the possibility of the existence of somatic mutations. We also demonstrated that our algorithm has superior specificity and sensitivity compared with existing methods, as determined based on a simulation, the TCGA Mutation Calling Benchmark 4 datasets and data from the COLO-829 cell line. AVAILABILITY AND IMPLEMENTATION: The HapMuC source code is available from http://github.com/usuyama/hapmuc. PMID- 25123904 TI - Cordova: web-based management of genetic variation data. AB - Cordova is an out-of-the-box solution for building and maintaining an online database of genetic variations integrated with pathogenicity prediction results from popular algorithms. Our primary motivation for developing this system is to aid researchers and clinician-scientists in determining the clinical significance of genetic variations. To achieve this goal, Cordova provides an interface to review and manually or computationally curate genetic variation data as well as share it for clinical diagnostics and the advancement of research. AVAILABILITY AND IMPLEMENTATION: Cordova is open source under the MIT license and is freely available for download at https://github.com/clcg/cordova. PMID- 25123905 TI - SCDFinder, a web-based tool for the identification of putative novel ATM and ATR targets. AB - MOTIVATION: The S/TQ cluster domain (SCD) constitutes a new type of protein domain that is not defined by sequence similarity but by the presence of multiple S/TQ motifs within a variable stretch of amino acids. SCDs are recognized targets for DNA damage response (DDR) kinases like ATM and ATR. Characterizing DDR targets is of significant interest. The aim of this work was to develop a web based tool to allow for easy identification and visualization of SCDs within specific proteins or in whole proteome sets, a feature not supported by current domain and motif search tools. RESULTS: We have developed an algorithm that (i) generates a list of all proteins in an organism containing at least one user defined SCD within their sequence, or (ii) identifies and renders a visual representation of all user-defined SCDs present in a single sequence or batch of sequences. AVAILABILITY AND IMPLEMENTATION: The application was developed using Pearl and Python, and is available at the following URL: http://ustbioinfo.webfactional.com/scd/. PMID- 25123906 TI - Response to: Reflections on competency-based education and training for surgical residents. PMID- 25123908 TI - The power of approximate degrees of freedom tests in heteroscedastic factorial designs. AB - Several viable approaches have been proposed for conducting factorial analysis when the homogeneous variances assumption is violated. Although robust type I error control and excellent power performance are desirable properties of a test procedure for making statistical inferences, the corresponding power calculations must also be considered to extend its applicability in planning research studies. This article presents the power functions of two approximate degrees of freedom tests within the context of two-way factorial designs. Both theoretical examination and empirical investigation are performed to demonstrate the underlying features of the two approaches. Simulation results showed that the suggested procedures provide remarkably good approximations over a wide range of model configurations. In view of the overall accuracy, the power functions are recommended for enhancing the usefulness of the associated test procedures. To facilitate the adoption of the suggested methodology in factorial research designs, computer code is presented for implementing the described power calculations. PMID- 25123907 TI - Letter to the editor response. PMID- 25123909 TI - POLYMAT-C: a comprehensive SPSS program for computing the polychoric correlation matrix. AB - We provide a free noncommercial SPSS program that implements procedures for (a) obtaining the polychoric correlation matrix between a set of ordered categorical measures, so that it can be used as input for the SPSS factor analysis (FA) program; (b) testing the null hypothesis of zero population correlation for each element of the matrix by using appropriate simulation procedures; (c) obtaining valid and accurate confidence intervals via bootstrap resampling for those correlations found to be significant; and (d) performing, if necessary, a smoothing procedure that makes the matrix amenable to any FA estimation procedure. For the main purpose (a), the program uses a robust unified procedure that allows four different types of estimates to be obtained at the user's choice. Overall, we hope the program will be a very useful tool for the applied researcher, not only because it provides an appropriate input matrix for FA, but also because it allows the researcher to carefully check the appropriateness of the matrix for this purpose. The SPSS syntax, a short manual, and data files related to this article are available as Supplemental materials that are available for download with this article. PMID- 25123910 TI - Magnetic resonance imaging-based diagnosis of progressive multifocal leukoencephalopathy in a patient with non-Hodgkin lymphoma after therapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab. PMID- 25123911 TI - Reply to Luzzatto et al. (2014): "Comment on 'Genetic evidence and new morphometric data as essential tools to identify the Patagonian seahorse Hippocampus patagonicus (Pisces, Syngnathidae), Gonzalez et al. (2014)'". PMID- 25123912 TI - Surface free energy of the human skin and its critical surface tension of wetting in the skin/surfactant aqueous solution/air system. AB - BACKGROUND/PURPOSE: The purpose of these studies was to determine the surface free energy of the human skin and its critical surface tension of wetting in the skin--surfactant aqueous solution--air system in relation to different types of surfactants. METHODS: The surface free energy of the skin and its components was calculated using the equilibrium advancing contact angle values of water, formamide, and diiodomethane on the forearm skin surface. Next, taking into account the measured values of the contact angle of aqueous solutions of SDDS, CTAB, TX-100 and TX-114 on the skin surface and data of their surface tension, the critical surface tension of the skin wetting was determined. RESULTS: We can classify the skin surface as low-energetic one. The critical surface tension of the skin wetting depends on the type of surfactant. CONCLUSION: It is possible to determine the critical surface tension of the human skin wetting on the basis of the values of the contact angle of aqueous solutions of surfactants and their surface tension. In this respect, nonionic surfactants seem to be the most appropriate. PMID- 25123920 TI - The chloridomolybdenum(III) cluster in [BMIm]4[AgMo10Cl35] with infinite chains of Ag(+)-linked [Mo10Cl35](5-) wheels. AB - [BMIm]4[AgMo10Cl35] is prepared by reaction of MoCl5 and elemental silver in the ionic liquid [BMIm][AlCl4] ([BMIm(+)]: 1-butyl-4-methylimidazolium). Surprisingly, elemental silver is oxidized under these conditions. The title compound contains a new wheel-shaped [Mo10Cl35](5-) chlorido molybdenum(iii) species with five pairs of Mo-Mo bonds. The Mo-Mo distances are found to be 263 pm on average. The [Mo10Cl35](5-) wheels exhibit a maximum opening of 558 pm in diameter. They are interlinked via Ag(+) to form infinite [AgMo10Cl35](4-) chains. The title compound is characterized by single crystal structure analysis, EDX, FT-IR and UV-Vis spectroscopy. The wheel-type structure and Ag(+) linkage to infinite chains are a new aspect of halogenido metalates and low-valence molybdenum compounds. PMID- 25123919 TI - A simple technique for reconstruction of medial patellofemoral ligament with bone fascia tunnel fixation at the medial margin of the patella: a 6-year-minimum follow-up study. AB - BACKGROUND: Medial patellofemoral ligament (MPFL) reconstruction has become an accepted technique to treat patellofemoral instability, and numerous surgical techniques have been described to reconstruct the MPFL. We describe a MPFL reconstruction procedure where bone-fascia tunnel fixation occurs at the medial margin of the patella for recurrent patellar dislocation. OBJECTIVE: MPFL reconstruction is the preferred operative treatment for recurrent patellar dislocation. The purpose of this study was to report a simple technique for reconstruction of medial patellofemoral ligament with bone-fascia tunnel fixation at the medial margin of the patella for recurrent patellar dislocation and to evaluate the results at 6-year-minimum follow-up. METHODS: The study included 65 patients (28 males, 37 females; mean age, 29.4 +/- 5.6 years) who underwent MPFL reconstruction using the bone-fascia tunnel fixation at the medial margin of the patella technique and who were followed for a mean duration of 78.5 +/- 3.8 months. Objective assessment, Kujala scale, Lysholm score, and Tegner activity score were obtained preoperatively and at the time of final follow-up. RESULTS: There were no patellar complications, including redislocation, in the present study. The congruence angle had significant improvement from 19.2 degrees +/- 6.3 degrees before surgery to -6.03 degrees +/- 0.50 degrees at the last follow-up. The lateral patellar angle had significant improvement from -6.9 degrees +/- 3.5 degrees before surgery to 5.1 degrees +/- 2.4 degrees at the last follow-up. The patellar tilt angle had significant improvement from 24.5 degrees +/- 5.2 degrees before surgery to 12.30 degrees +/- 1.90 degrees at the last follow-up. The Kujala score was significantly increased from 52.9 +/- 3.2 points preoperatively to 90.1 +/- 5.8 points postoperatively (P < 0.05). The mean Lysholm score was significantly increased from 47.2 +/- 5.2 to 92.5 +/- 6.2 points postoperatively (P < 0.05). The Tegner activity score improved overall from 3.1 +/- 0.6 points to 5.8 +/- 0.9 points at follow-up. CONCLUSION: We have done a simple technique where the MPFL is reconstructed safely to avoid patella fracture, anatomically to restore physiological kinematics and stability, and economically to reduce costs with bone-fascia tunnel fixation at the medial margin of the patella. PMID- 25123918 TI - Genetic architecture of ALS in Sardinia. AB - Conserved populations, such as Sardinians, displaying elevated rates of familial or sporadic amyotrophic lateral sclerosis (ALS) provide unique information on the genetics of the disease. Our aim was to describe the genetic profile of a consecutive series of ALS patients of Sardinian ancestry. All ALS patients of Sardinian ancestry, identified between 2008 and 2013 through the Italian ALS Genetic Consortium, were eligible to be included in the study. Patients and controls underwent the analysis of TARDBP, C9ORF72, SOD1, and FUS genes. Genetic mutations were identified in 155 out of 375 Sardinian ALS cases (41.3%), more commonly the p.A382T and p.G295S mutations of TARDBP and the GGGGCC hexanucleotide repeat expansion of C9ORF72. One patient had both p.G295S and p.A382T mutations of TARDBP and 8 carried both the heterozygous p.A382T mutation of TARDBP and a repeat expansion of C9ORF72. Patients carrying the p.A382T and the p.G295S mutations of TARDBP and the C9ORF72 repeat expansion shared distinct haplotypes across these loci. Patients with cooccurrence of C9ORF72 and TARDBP p.A382T missense mutation had a significantly lower age at onset and shorter survival. More than 40% of all cases on the island of Sardinia carry a mutation of an ALS-related gene, representing the highest percentage of ALS cases genetically explained outside of Scandinavia. Clinical phenotypes associated with different genetic mutations show some distinctive characteristics, but the heterogeneity between and among families carrying the same mutations implies that ALS manifestation is influenced by other genetic and nongenetic factors. PMID- 25123921 TI - Cell responses to metallic nanostructure arrays with complex geometries. AB - Metallic nanopillar/nanowires are emerging as promising platforms for biological applications, as they allow for the direct characterization and regulation of cell function. Herein we study the response of cells to a versatile nanopillar platform. Nanopillar arrays of various shape, size, and spacing and different nanopillar-substrate interfacial strengths were fabricated and interfaced with fibroblasts and several unique cell-nanopillar interactions were observed using high resolution scanning electron microscopy. Nanopillar penetration, engulfment, tilting, lift off and membrane thinning, were observed by manipulating nanopillar material, size, shape and spacing. These unique cell responses to various nanostructures can be employed for a wide range of applications including the design of highly sensitive nano-electrodes for single-cell probing. PMID- 25123917 TI - Neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD)--a controlled multicenter study of a non-pharmacological treatment approach. AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and has often a chronic course persisting into adulthood. However, up to 30% of children treated with stimulants either fail to show an improvement or suffer adverse side effects, including decreased appetite, insomnia and irritability and there is no evidence of long term efficacy of stimulants for ADHD. A series of studies has shown that neurofeedback is an effective additional or alternative treatment for children with ADHD, leading to e.g. significant and stable improvement in behavior, attention and IQ. Significant treatment effects of neurofeedback have also been verified in meta analyses. Most of the trials, however, have been criticized for methodological difficulties, particularly lacking appropriate control conditions and number of patients included. This randomized study examines the efficacy of slow cortical potentials (SCP) -neurofeedback, controlling unspecific effects of the setting by comparing two active treatment modalities. METHODS/DESIGN: A total of 144 patients with ADHD, older than six and younger than ten years, in some cases with additional pharmacological treatment, are included in this trial. In five trial centres patients are treated either with SCP-feedback or electromyographic (EMG) feedback in 25 sessions within 3 months. A comprehensive test battery is conducted before and after treatment and at follow-up 6 month later, to assess core symptoms of ADHD, general psychopathology, attentional performance, comorbid symptoms, intelligence, quality of life and cortical arousal. DISCUSSION: The efficacy of SCP-feedback training for children with ADHD is evaluated in this randomized controlled study. In addition to behavior ratings and psychometric tests neurophysiological parameters serve as dependent variables. Further, the choice of EMG-biofeedback as an active control condition is debated. TRIALS REGISTRATION: Current Controlled Trials ISRCTN76187185. Registered 5 February 2009. PMID- 25123922 TI - Surface chemistry dependent immunostimulative potential of porous silicon nanoplatforms. AB - Nanoparticles (NPs) have been suggested for immunotherapy applications in order to optimize the delivery of immuno-stimulative or -suppressive molecules. However, low attention towards the impact of the NPs' physicochemical properties has presented a major hurdle for developing efficient immunotherapeutic agents. Here, the effects of porous silicon (PSi) NPs with different surface chemistries were evaluated on human monocyte-derived dendritic cells (MDDCs) and lymphocytes in order to highlight the importance of the NPs selection in immuno-stimulative or -suppressive treatment. Although all the PSi NPs showed high biocompatibility, only thermally oxidized PSi (TOPSi) and thermally hydrocarbonized PSi (THCPSi) NPs were able to induce very high rate of immunoactivation by enhancing the expression of surface co-stimulatory markers of the MDDCs (CD80, CD83, CD86, and HLA-DR), inducing T-cell proliferation, and also the secretion of interleukins (IL-1beta, IL-4, IL-6, IL-10, IL-12, IFN-gamma, and TNF-alpha). These results indicated a balanced increase in the secretion of Th1, Th2, and Treg cytokines. Moreover, undecylenic acid functionalized THCPSi, as well as poly(methyl vinyl ether-alt-maleic acid) conjugated to (3-aminopropyl)triethoxysilane functionalized thermally carbonized PSi and polyethyleneimine conjugated undecylenic acid functionalized THCPSi NPs showed moderate immunoactivation due to the mild increase in the above-mentioned markers. By contrast, thermally carbonized PSi (TCPSi) and (3-aminopropyl)triethoxysilane functionalized TCPSi NPs did not induce any immunological responses, suggesting that their application could be in the delivery of immunosuppressive molecules. Overall, our findings suggest all the NPs containing more nitrogen or oxygen on the outermost backbone layer have lower immunostimulatory effect than NPs with higher C-H structures on the surface. PMID- 25123923 TI - The osteogenic differentiation of SSEA-4 sub-population of human adipose derived stem cells using silicate nanoplatelets. AB - How to surpass in vitro stem cell differentiation, reducing cell manipulation, and lead the in situ regeneration process after transplantation, remains to be unraveled in bone tissue engineering (bTE). Recently, we showed that the combination of human bone marrow stromal cells with bioactive silicate nanoplatelets (sNPs) promotes the osteogenic differentiation without the use of standard osteogenic inductors. Even more, using SSEA-4(+) cell-subpopulations (SSEA-4(+)hASCs) residing within the adipose tissue, as a single-cellular source to obtain relevant cell types for bone regeneration, was also proposed. Herein, sNPs were used to promote the osteogenic differentiation of SSEA-4(+)hASCs. The interactions between SSEA-4(+)hASCs and sNPs, namely the internalization pathway and effect on cells osteogenic differentiation, were evaluated. SNPs below 100 MUg/mL showed high cytocompatibility and fast internalization via clathrin mediated pathway. SNPs triggered an overexpression of osteogenic-related markers (RUNX2, osteopontin, osteocalcin) accompanied by increased alkaline phosphatase activity and deposition of a predominantly collagen-type I matrix. Consequently, a robust matrix mineralization was achieved, covering >90% of the culturing surface area. Overall, we demonstrated the high osteogenic differentiation potential of SSEA-4(+)hASCs, further enhanced by the addition of sNPs in a dose dependent manner. This strategy endorses the combination of an adipose-derived cell-subpopulation with inorganic compounds to achieve bone matrix-analogs with clinical relevance. PMID- 25123924 TI - Multiscale patterned transplantable stem cell patches for bone tissue regeneration. AB - Stem cell-based therapy has been proposed as an enabling alternative not only for the treatment of diseases but also for the regeneration of tissues beyond complex surgical treatments or tissue transplantation. In this study, we approached a conceptual platform that can integrate stem cells into a multiscale patterned substrate for bone regeneration. Inspired by human bone tissue, we developed hierarchically micro- and nanopatterned transplantable patches as synthetic extracellular matrices by employing capillary force lithography in combination with a surface micro-wrinkling method using a poly(lactic-co-glycolic acid) (PLGA) polymer. The multiscale patterned PLGA patches were highly flexible and showed higher tissue adhesion to the underlying tissue than did the single nanopatterned patches. In response to the anisotropically multiscale patterned topography, the adhesion and differentiation of human mesenchymal stem cells (hMSCs) were sensitively controlled. Furthermore, the stem cell patch composed of hMSCs and transplantable PLGA substrate promoted bone regeneration in vivo when both the micro- and nanotopography of the substrate surfaces were synergistically combined. Thus, our study concludes that multiscale patterned transplantable stem cell patches may have a great potential for bone regeneration as well as for various regenerative medicine approaches. PMID- 25123925 TI - Effective ovarian stimulation in a patient with resistant ovary syndrome and antigonadotrophin antibodies. AB - PROBLEM: We report on a successful ovarian stimulation and pregnancy in a patient with 'resistant ovary syndrome' (ROS) and antigonadotrophin antibodies. ROS is characterized by high endogenous gonadotrophins, low estradiol, normal ovarian antral follicle counts and normal antimuellerian hormone values. METHOD OF STUDY: After cyclical hormone treatment, downregulation with GnRH analogue and ICSI procedure followed. Granulosa cells were treated with LH, FSH or hMG and expression of receptors for FSH, LH, oestrogen receptor beta (ERb) and progesterone receptor A (PR-A) was determined. Serum of the patient was analysed for antibodies directed against hMG. RESULTS: After fertilization of ten metaphase II oocytes and transfer of two blastocysts, a singleton pregnancy was established. Stimulation of granulosa cells with FSH, LH and hMG upregulated ERb and PR-A. Dot blot analysis showed strong reactivity with hMG but not with recFSH. CONCLUSION: This patient with normal expression of gonadotrophin receptors showed antibodies directed to hMG but not to recFSH. PMID- 25123926 TI - Cerebellar abnormalities in Huntington's disease: a role in motor and psychiatric impairment? AB - The cerebellum has received limited attention in Huntington's disease (HD), despite signs of possible cerebellar dysfunction, including motor incoordination and impaired gait, which are currently attributed to basal ganglia atrophy and disrupted fronto-striatal circuits. This study is the first to investigate a potential contribution of macro- and microstructural cerebellar damage to clinical manifestations of HD. T1- and diffusion-weighted 3T magnetic resonance imaging (MRI) scans were obtained from 12 controls and 22 early-stage HD participants. Manual delineation and voxel-based morphometry were used to assess between-group differences in cerebellar volume, and diffusion metrics were compared between groups within the cerebellar gray and white matter. Associations between these imaging measures and clinical scores were examined within the HD group. Reduced paravermal volume was detected in HD compared with controls using voxel-based morphometry (P < 0.05), but no significant volumetric differences were found using manual delineation. Diffusion abnormalities were detected in both cerebellar gray matter and white matter. Smaller cerebellar volumes, although not significantly reduced, were significantly associated with impaired gait and psychiatric morbidity and of borderline significance with pronate/supinate-hand task performance. Abnormal cerebellar diffusion was associated with increased total motor score, impaired saccade initiation, tandem walking, and timed finger tapping. In conclusion, atrophy of the paravermis, possibly encompassing the cerebellar nuclei, and microstructural abnormalities within the cerebellum may contribute to HD neuropathology. Aberrant cerebellar diffusion and reduced cerebellar volume together associate with impaired motor function and increased psychiatric symptoms in stage I HD, potentially implicating the cerebellum more centrally in HD presentation than previously recognized. PMID- 25123927 TI - [Nostalgia and the functions of autobiographical memory]. AB - BACKGROUND: Current research on autobiographical memory distinguishes between a self function, a directive function, and a social function of autobiographical memory. From a lifespan perspective, the use of autobiographical memory for these functions is expected to decrease with age. The present study extended these functions by the function of nostalgia: Often triggered by negative emotions, remembering personal and positive experiences might, among others, enhance positive effects. This emotion-regulating function is expected to become more important in old age. MATERIAL AND METHODS: In the present study 273 adults (aged between 19 and 90 years) completed the Thinking About Life Experiences Questionnaire (TALE) as well as 11 newly developed items to assess the nostalgia function. RESULTS: Exploratory and confirmatory factor analyses supported a four factor model reflecting the presumed self, directive, social, and nostalgia functions of autobiographical memory. The results showed a decrease in the use of autobiographical memory for self, directive and social functions with increasing age, whereas the nostalgia function followed a U-shaped pattern. PMID- 25123928 TI - Geographic and racial-ethnic differences in satisfaction with and perceived benefits of mental health services. AB - OBJECTIVE: This study examined whether racial-ethnic differences in satisfaction with and perceived benefits from mental health services vary by geographic region among U.S. adults. METHODS: Drawn from the Collaborative Psychiatric Epidemiology Surveys (CPES), selected samples consisted of 2,160 adults age 18 and older from diverse racial-ethnic groups (Asian, black, Hispanic/Latino, and white) who had used mental health services in the past 12 months. Generalized linear model analysis was conducted for the United States as a whole and separately by geographic region (Northeast, South, Midwest, and West) after adjustment for covariates. RESULTS: In the national sample, no significant main effects of race ethnicity and geographic region were found in either satisfaction with or perceived benefits from mental health services. In the stratified analyses for geographic regions, however, significant racial-ethnic differences were observed in the West; blacks in the West were significantly more likely to report higher satisfaction and perceived benefits, whereas Hispanics/Latinos in the West were significantly less likely to do so. CONCLUSIONS: The findings suggest that there are regional variations of racial-ethnic differences in satisfaction with and perceived benefits from mental health services among U.S. adults and that addressing needs of Hispanics/Latinos in the West may help reduce racial-ethnic disparities in mental health care. Clinical and policy implications are discussed. PMID- 25123929 TI - Mitotic DNA damages induced by carbon-ion radiation incur additional chromosomal breaks in polyploidy. AB - Compared with low linear energy transfer (LET) radiation, carbon-ion radiation has been proved to induce high frequency of more complex DNA damages, including DNA double strands (DSBs) and non-DSB clustered DNA lesions. Chemotherapeutic drug doxorubicin has been reported to elicit additional H2AX phosphorylation in polyploidy. Here, we investigated whether mitotic DNA damage induced by high-LET carbon-ion radiation could play the same role. We demonstrate that impairment of post-mitotic G1 and S arrest and abrogation of post-mitotic G2-M checkpoint failed to prevent mis-replication of damaged DNA and mis-separation of chromosomes. Meanwhile, mitotic slippage only nocodazole-related, cytokinesis failure and cell fusion collectively contributed to the formation of binucleated cells. Chk1 and Cdh1 activation was inhibited when polyploidy emerged in force, both of which are critical components for mitotic exit and cytokinesis. Carbon ion radiation irrelevant of nocodazole incurred additional DNA breaks in polyploidy, manifesting as structural and numerical karyotype changes. The proliferation of cells given pre-synchronization and radiation was completely inhibited and cells were intensely apoptotic. Since increased chromosomal damage resulted in extensive H2AX phosphorylation during polyploidy, we propose that the additional gamma-H2AX during polyploidy incurred by carbon-ion radiation provides a final opportunity for these dangerous and chromosomally unstable cells to be eliminated. PMID- 25123930 TI - Molecular differentiation of Central European blowfly species (Diptera, Calliphoridae) using mitochondrial and nuclear genetic markers. AB - A challenging step in medical, veterinary and forensic entomology casework is the rapid and accurate identification of insects to estimate the period of insect activity (PIA), which usually approximates the post-mortem interval (PMI). The morphological identification of insect evidence is hampered by species similarities, especially at the early larval stages. However, DNA-based species identification is more accurate and reliable. In this study, we improved the suitability and efficacy of the standard mitochondrial cytochrome c oxidase subunit I (COI) barcode region of 658 bp combined with an additional region of 616 bp of the same gene. We also tested the usefulness of other mitochondrial and nuclear loci, such as the non-coding region included in mitochondrial Cyt-b tRNA(ser)-ND1 (495-496 bp) and the second internal transcribed spacer (ITS2) region of nuclear ribosomal DNA (rDNA) (310-337 bp). We classified a total of 54 specimens from five blowfly species belonging to three Calliphoridae genera commonly found in Central Europe: Phormia (P. regina), Calliphora (C. vicina) and Lucilia (L. sericata, L. ampullacea and L. caesar). Additionally included were the Cyt-b (307 bp) sequences for P. regina species and GenBank recorded information about the studied loci for select species. The results revealed the robustness of COI (616 bp) and ITS2 (310-337 bp) as diagnostic tools to be added to the widely established COI barcode (658 bp). Their higher discriminatory power allows for more precise and reliable identifications, even within more complex genera (Lucilia). This work also contributes new nucleotide sequences that are useful for accurate species diagnosis and new sequence data of Calliphoridae interspecific variability in the European Westphalia region (Germany). PMID- 25123932 TI - Pyridoxine-derived organoselenium compounds with glutathione peroxidase-like and chain-breaking antioxidant activity. AB - One of the vitamin B6 vitamers, pyridoxine, was modified to incorporate selenium in various oxidation states in place of the methyl group in position 2. Such compounds were conveniently accessed by treatment of bis-4,5-(carboethoxy)-2-iodo 3-pyridinol with disodium diselenide and LiAlH4 -reduction. After work-up, selone 7 was isolated in good yield as an air-stable crystalline material. Hydrogen bonding to the neighboring hydroxyl group, as revealed by the short intramolecular Se???H distance in the crystal structure is likely to provide extra stabilization to the compound. Computational studies showed that selone 7 is more stable than the corresponding selenol tautomer by 12.2 kcal mol(-1) . Hydrogen peroxide oxidation of the selone 7 afforded diselenide 12, and, on further oxidation, seleninic acid 13. Treatment of the seleninic acid with thiophenol provided an isolable selenosulfide 14. The glutathione peroxidase-like properties of the pyridoxine-derived compounds were assessed by using the coupled reductase method. Seleninic acid 13 was found to be twofold more active than ebselen. The chain-breaking capacity of the pyridoxine compounds were studied in a water/chlorobenzene membrane model containing linoleic acid as an oxidizable substrate and N-acetylcysteine as a thiol reducing agent. Diselenide 15 could match alpha-tocopherol when it comes to reactivity towards peroxyl radicals and inhibition time. PMID- 25123933 TI - The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) survey: provider practices and beliefs about allergen immunotherapy. AB - BACKGROUND: The practices and beliefs of the provider specialties that treat allergic rhinoconjunctivitis (ARC) with allergen immunotherapy (AIT) may vary. METHODS: A telephone survey of 500 randomly selected health care practitioners in 7 specialties, conducted in 2012. RESULTS: AIT was provided as a subcutaneous injection (SCIT) by 91% of allergist/immunologists, 54% of otolaryngologists, and 18% to 24% of other specialties. Otolaryngologists were the most frequent providers of sublingual drops of AIT (SLIT; 33%), compared to 2% to 10% of other specialties. AIT was recommended for adults with allergic rhinoconjunctivitis by 100% of allergist/immunologists vs 62% to 84% of the other specialties (p < 0.001). The primary reason for recommending AIT for adults (52%) or children (46%) was that other therapies did not work. Between 48% (nurse practitioners/physician assistants) and 93% (allergist/immunologists) of practitioners always or often decreased symptomatic medications over the course of AIT treatment. Most practitioners in all specialties (82-100%) thought that AIT was appropriate for patients with severe allergy symptoms. Significantly more allergist/immunologists and otolaryngologists than other specialists thought AIT was appropriate for mild allergy symptoms (p < 0.001 and p = 0.004, respectively, vs other specialties). Significantly more allergist/immunologists than other specialists thought that AIT was more effective than symptomatic medications (p < 0.001), could reduce the further development of allergies (p = 0.03), and could prevent the development of asthma. CONCLUSION: SCIT was more frequently provided than SLIT by all the specialties. Otolaryngologists were the most likely to offer SLIT, while very few allergist/immunologists offered SLIT. Allergist/immunologists differed from other specialties in some beliefs about the effectiveness of AIT. PMID- 25123931 TI - Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells. AB - OBJECTIVE: Helicobacter pylori strains that express the oncoprotein CagA augment risk for gastric cancer. However, the precise mechanisms through which cag(+) strains heighten cancer risk have not been fully delineated and model systems that recapitulate the gastric niche are critical for understanding pathogenesis. Gastroids are three-dimensional organ-like structures that provide unique opportunities to study host-H. pylori interactions in a preclinical model. We used gastroids to inform and direct in vitro studies to define mechanisms through which H. pylori modulates expression of the cancer-associated tight junction protein claudin-7. DESIGN: Gastroids were infected by luminal microinjection, and MKN28 gastric epithelial cells were cocultured with H. pylori wild-type cag(+) strains or isogenic mutants. beta-catenin, claudin-7 and snail localisation was determined by immunocytochemistry. Proliferation was assessed using 5-ethynyl-2' deoxyuridine, and levels of claudin-7 and snail were determined by western blot and flow cytometry. RESULTS: Gastroids developed into a self-organising differentiation axis and H. pylori induced mislocalisation of claudin-7 and increased proliferation in a CagA- and beta-catenin-dependent manner. In MKN28 cells, H pylori-induced suppression of claudin-7 was regulated by beta-catenin and snail. Similarly, snail expression was increased and claudin-7 levels were decreased among H. pylori-infected individuals. CONCLUSIONS: H. pylori increase proliferation in a strain-specific manner in a novel gastroid system. H. pylori also alter expression and localisation of claudin-7 in gastroids and human epithelial cells, which is mediated by beta-catenin and snail activation. These data provide new insights into molecular interactions with carcinogenic potential that occur between H. pylori and epithelial cells within the gastric niche. PMID- 25123934 TI - Towards elucidating the stability, dynamics and architecture of the nucleosome remodeling and deacetylase complex by using quantitative interaction proteomics. AB - The nucleosome remodeling and deacetylase (NuRD) complex is an evolutionarily conserved chromatin-associated protein complex. Although the subunit composition of the mammalian complex is fairly well characterized, less is known about the stability and dynamics of these interactions. Furthermore, detailed information regarding protein-protein interaction surfaces within the complex is still largely lacking. Here, we show that the NuRD complex interacts with a number of substoichiometric zinc finger-containing proteins. Some of these interactions are salt-sensitive (ZNF512B and SALL4), whereas others (ZMYND8) are not. The stoichiometry of the core subunits is not affected by high salt concentrations, indicating that the core complex is stabilized by hydrophobic interactions. Interestingly, the RBBP4 and RBBP7 proteins are sensitive to high nonionic detergent concentrations during affinity purification. In a subunit exchange assay with stable isotope labeling by amino acids in cell culture (SILAC)-treated nuclear extracts, RBBP4 and RBBP7 were identified as dynamic core subunits of the NuRD complex, consistent with their proposed role as histone chaperones. Finally, using cross-linking MS, we have uncovered novel features of NuRD molecular architecture that complement our affinity purification-MS/MS data. Altogether, these findings extend our understanding of MBD3-NuRD structure and stability. STRUCTURED DIGITAL ABSTRACT: MBD3 physically interacts with ZNF512B, HDAC1, ZMYND8, GATAD2B, SALL4, GATAD2A, ZNF592, MTA3, ZNF687, CDK2AP1, CHD3, ZNF532, HDAC2, MTA2, CHD4, MTA1, KPNA2, CHD5, RBBP4 and RBBP7 by pull down (View interaction) CDK2AP1 physically interacts with MBD3, MTA3, HDAC2, GATAD2A, CHD4, CDK2AP1, MTA2, HDAC1, MTA1, CHD3, GATAD2B, MBD2, RBBP4 and RBBP7 by pull down (View interaction) MBD3 physically interacts with MTA2, MTA3, RBBP4, RBBP7, HDAC2, HDAC1, CHD4, CHD3 and MTA1 by cross-linking study (View interaction). PMID- 25123936 TI - Detection of cyanobacterial neurotoxin beta-N-methylamino-l-alanine within shellfish in the diet of an ALS patient in Florida. AB - Cyanobacteria produce the neurotoxic amino acid beta-N-methylamino-l-alanine (BMAA), which in contaminated marine waters has been found to accumulate in shellfish. Exposure to BMAA has been associated with an increased risk of neurodegenerative disease. Analysis of blinded samples found BMAA to be present in neuroproteins of individuals who died from ALS and ALS/PDC, but generally not in the brains of patients who died of causes unrelated to neurodegeneration or Huntington's disease, an autosomal dominant neurodegenerative disease. We here report support for a link between a patient with ALS and chronic exposure to the cyanobacterial neurotoxin BMAA via shellfish consumption. The patient had frequently eaten lobsters collected in Florida Bay for approximately 30 years. LC MS/MS analysis of two lobsters which this ALS patient had placed in his freezer revealed BMAA at concentrations of 27 and 4 MUg/g, respectively, as well as the presence of 2,4-diaminobutyric acid (DAB), a BMAA isomer. Two additional lobsters recently collected from Florida Bay also contained the neurotoxins BMAA and DAB. These data suggest that invertebrates collected in water where cyanobacterial blooms are present, if consumed, may result in direct human exposure to these neurotoxic amino acids. The data support the assertion that prolonged exposure to BMAA may have played a role in the etiology of ALS in this patient. PMID- 25123935 TI - The necrotrophic effector protein SnTox3 re-programs metabolism and elicits a strong defence response in susceptible wheat leaves. AB - BACKGROUND: The fungus Stagonospora nodorum is a necrotrophic pathogen of wheat. It causes disease by secreting proteinaceous effectors which interact with proteins encoded by dominant susceptibility genes in the host. The outcome of these interactions results in necrosis, allowing the fungus to thrive on dead plant material. The mechanisms of these effectors though are poorly understood. In this study, we undertake a comprehensive transcriptomics, proteomic and metabolomic approach to understand how a susceptible wheat cultivar responds to exposure to the Stagonospora nodorum effector protein SnTox3. RESULTS: Microarray and proteomic studies revealed that SnTox3 strongly induced responses consistent with those previously associated with classical host defence pathways including the expression of pathogenicity-related proteins and the induction of cell death. Collapse of the photosynthetic machinery was also apparent at the transcriptional and translational level. SnTox3-infiltrated wheat leaves also showed a strong induction of enzymes involved in primary metabolism consistent with increases in hexoses, amino acids and organic acids as determined by primary metabolite profiling. Methionine and homocysteine metabolism was strongly induced upon exposure to SnTox3. Pathogenicity in the presence of homocysteine was inhibited confirming that the compound has a role in plant defence. Consistent with the strong defence responses observed, secondary metabolite profiling revealed the induction of several compounds associated with plant defence, including the phenylpropanoids chlorogenic acid and feruloylquinic acid, and the cyanogenic glucoside dhurrin. Serotonin did not accumulate subsequent to SnTox3 infiltration. CONCLUSIONS: These data support the theory that the SnTox3 effector protein elicits a host cell death response to facilitate the pathogen's necrotrophic infection cycle. Our data also demonstrate that the mechanism of SnTox3 appears distinct from the previously characterised Stagonospora nodorum effector SnToxA. Collectively, this comprehensive analysis has advanced our understanding of necrotrophic effector biology and highlighted the complexity of effector-triggered susceptibility. PMID- 25123937 TI - Complex formation of Sn(II) with glycine: an IR, DTA/TGA and DFT investigation. AB - The novel Sn(Gly)2?H2O complex compound has been synthesized and characterized by TGA, IR and Raman spectroscopy. Molecular spectroscopy and ab initio simulation have given the evidence of glycine molecule being coordinated to Sn(II) as bidentate chelating ligand by oxygen atom of carboxyl group and nitrogen atom of amino group. Water molecule is bonded with amino and carboxylic groups by hydrogen bonds in the out sphere. The M06, TPSS, TPSSm, TPSSh and revTPSS density functionals have been tested for calculation of structural and vibrational data. The vibrational assignment of experimental IR and Raman and simulated spectra has been carried out. The TPSS and TPSSm density functionals and Def2-TZVP basis set have provided the most accurate results. PMID- 25123938 TI - Charge-transfer complexes of 4-methylpiperidine with sigma- and pi-acceptors. AB - The solid charge-transfer (CT) molecular complexes formed in the reaction of the electron donor 4-methylpiperidine (4MP) with the sigma-electron acceptor iodine and pi-acceptors 7,7,8,8-tetracyanoquinodimethane (TCNQ), 2,3-dichloro-5,6 dicyano-1,4-benzoquinone (DDQ) and 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TBCHD) have been investigated spectrophotometrically in chloroform at 25 degrees C. These were characterized through electronic and infrared spectra as well as elemental and thermal analysis. The obtained results showed that the formed solid CT-complexes have the formulas [(4MP) I](+)I(-)3, [(4MP)(DDQ)2] and [(4MP)(TBCHD)] and with TCNQ the adduct [TCMPQDM] is obtained through N substitution reaction in full agreement with the known reaction stoichiometries in solution as well as the elemental measurements. The formation constant KCT, molar extinction coefficient epsilonCT, free energy change DeltaG(0), CT energy ECT and the ionization potential Ip have been calculated for the CT-complexes [(4MP) I](+)I(-)3, [(4MP)(DDQ)2] and [(4MP)(TBCHD)]. PMID- 25123939 TI - Determination of trace amount of formaldehyde base on a bromate-Malachite Green system. AB - A novel catalytic kinetic spectrophotometric method for determination of trace amount of formaldehyde (FA) has been established, based on catalytic effect of trace amount of FA on the oxidation of Malachite Green (MG) by potassium bromate in presence of sulfuric acid medium, and was reported for the first time. The method was monitored by measuring the decrease in absorbance of MG at 617 nm and allowed a precise determination of FA in the range of 0.003-0.08 MUg mL(-1), with a limit of detection down to 1 ng mL(-1). The relative standard deviation of 10 replicate measurements was 1.63%. The method developed was approved to be sensitive, selective and accurate, and adopted to determinate free FA in samples directly with good accuracy and reproducibility. PMID- 25123940 TI - Spectroscopic analyses and studies on respective interaction of cyanuric acid and uric acid with bovine serum albumin and melamine. AB - In this work, the fluorescence quenching was used to study the interaction of cyanuric acid (CYA) and uric acid (UA) with bovine serum albumin (BSA) at two different temperatures (283 K and 310 K). The bimolecular quenching constant (Kq), apparent quenching constant (Ksv), effective binding constant (KA) and corresponding dissociation constant (KD), binding site number (n) and binding distance (r) were calculated by adopting Stern-Volmer, Lineweaver-Burk, Double logarithm and overlap integral equations. The results show that CYA and UA are both able to obviously bind to BSA, but the binding strength order is BSA+CYA3 months) in patients having external mesh support as part of CABG. METHODS: From October 25, 2010 through February 13, 2012, 21 patients had external mesh support of SVG grafts in addition to internal thoracic artery grafting to the Anterior Descending artery. Patients were invited to return for patency evaluation using Computerized Tomographic angiography (CTA) an average of 7.2 months post-operative (R = 3-14 months). RESULTS: 21 male patients (age 57+/- 9 years) underwent on-pump surgery. The eSVS Mesh was successfully placed on all SVGs. All grafts were determined patent intra-operative by transit time Doppler measurement and there were no operative revisions. There was no operative mortality. 12 of the 21 contacted patients returned for CTA, 8 non-returning patients contacted were alive and asymptomatic but refused to return due to travel restrictions or cost. One patient was lost to follow up. 11 returning patients underwent CTA. One patient was excluded (asymptomatic) due to elevated creatinine. Of the 23 anastomoses in 11 patients(Average: 2.09 grafts/patient) using SVG available for examination, 21 were patent (92%). CONCLUSIONS: In this retrospective non-randomized experience, the external mesh supported grafts displayed excellent intermediate patency. PMID- 25123949 TI - Role of BRAF molecular analysis in the management of papillary thyroid carcinoma: analysis of cytological and histological samples. AB - BACKGROUND: Although fine needle aspiration (FNA) is the standard diagnostic test for the characterization of a suspicious thyroid nodule, in some cases cytological evaluation is inconclusive. The aim of this study was to determine the role of BRAF mutation in aiding diagnosis and to verify whether archival cytological samples could be suitable for molecular analysis. METHODS: Eighty five patients with suspicious (Thy4) or follicular (Thy3) lesions on cytology were resubmitted to a second FNA for BRAF mutation analysis. Of these, 56 subsequently underwent surgery. The usefulness of archival samples for molecular analysis was also studied in a second cohort of 42 patients with a confirmed diagnosis of papillary thyroid carcinoma for whom both archived paraffin-embedded histological samples and cytological smears were available. A further 15 patients with paired fresh FNA and archived cytological and histological samples were recruited. RESULTS: BRAF mutation was found in the fresh FNA samples from 10 of 56 patients who had surgery with previous inconclusive cytology (4/45, 9%, Thy3 and 6/11, 55%, Thy4). The BRAF test showed a specificity and positive predictive value of 100% (26/26 and 10/10, respectively), sensitivity of 33% (10/30) and negative predictive value of 57% (26/46). There was absolute concordance between the BRAF results obtained with 42 histological and cytological archived samples. BRAF analysis on 15 archived cytological samples showed absolute concordance with histology, whereas there was one false negative on the matched fresh FNA. CONCLUSION: BRAF analysis is a highly specific test that can facilitate cytological diagnosis in some cases and can also be performed on archived cytological samples. PMID- 25123950 TI - Level of adherence to the GOLD strategy document for management of patients admitted to hospital with an acute exacerbation of COPD. AB - BACKGROUND AND OBJECTIVE: The Global initiative for chronic Obstructive Lung Disease (GOLD) strategy document has been available since 2001. Little is known about level of adherence to the GOLD document among hospital-based health professionals assessing and managing inpatients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The primary aim of the study was to evaluate the level of adherence among health professionals to GOLD. METHODS: A retrospective audit of medical histories was completed on a random sample of 240 patients admitted to hospital with a primary diagnosis of AECOPD within a calendar year. The audit evaluated adherence to GOLD recommendations on appropriateness of hospital and intensive care unit admissions as well as pharmacological and non-pharmacological management. RESULTS: High levels of adherence to indications for hospital admissions (97%), indications for intensive care unit admissions (100%) and prescription of bronchodilators (100%) were observed. However, antibiotics (45%) and oxygen therapy (68%) were over prescribed. Adherence to non-pharmacological management was poor in areas such as smoking cessation (25%) and pulmonary rehabilitation referrals (16%). Patients admitted under the care of the respiratory team were more likely (odds ratio = 2.6, 95% confidence interval: 1.3-5.4) to be referred to pulmonary rehabilitation than patients admitted under the general medicine team. CONCLUSIONS: Health professionals in the respiratory team had better adherence to GOLD as compared to health professionals in other teams. Nonetheless, pharmacological interventions were both appropriately prescribed and also over-prescribed, whereas non pharmacological interventions were used rarely, suggesting a need for practice review in these areas. PMID- 25123951 TI - Optimizing Rubisco and its regulation for greater resource use efficiency. AB - Rubisco catalyses the carboxylation of ribulose-1,5-bisphosphate (RuBP), enabling net CO2 assimilation in photosynthesis. The properties and regulation of Rubisco are not optimal for biomass production in current and projected future environments. Rubisco is relatively inefficient, and large amounts of the enzyme are needed to support photosynthesis, requiring large investments in nitrogen. The competing oxygenation of RuBP by Rubisco decreases photosynthetic efficiency. Additionally, Rubisco is inhibited by some sugar phosphates and depends upon interaction with Rubisco activase (Rca) to be reactivated. Rca activity is modulated by the chloroplast redox status and ADP/ATP ratios, thereby mediating Rubisco activation and photosynthetic induction in response to irradiance. The extreme thermal sensitivity of Rca compromises net CO2 assimilation at moderately high temperatures. Given its central role in carbon assimilation, the improvement of Rubisco function and regulation is tightly linked with irradiance, nitrogen and water use efficiencies. Although past attempts have had limited success, novel technologies and an expanding knowledge base make the challenge of improving Rubisco activity in crops an achievable goal. Strategies to optimize Rubisco and its regulation are addressed in relation to their potential to improve crop resource use efficiency and climate resilience of photosynthesis. PMID- 25123952 TI - Massive open online courses on health and medicine: review. AB - BACKGROUND: Massive open online courses (MOOCs) have become immensely popular in a short span of time. However, there is very little research exploring MOOCs in the discipline of health and medicine. OBJECTIVE: We aim to provide a review of MOOCs related to health and medicine offered by various MOOC platforms in 2013, by analyzing and comparing the various offerings, their target audience, typical length of course, and credentials offered. We also discuss opportunities and challenges presented by MOOCs in health and medicine. METHODS: Health and medicine-related MOOCs were gathered using several methods to ensure the richness and completeness of data. Identified MOOC platform websites were used to gather the lists of offerings. In parallel, these MOOC platforms were contacted to access official data on their offerings. Two MOOC aggregator sites (Class Central and MOOC List) were also consulted to gather data on MOOC offerings. Eligibility criteria were defined to concentrate on the courses that were offered in 2013 and primarily on the subject of health and medicine. All language translations in this paper were done using Google Translate. RESULTS: The search identified 225 courses, of which 98 were eligible for the review. Over half (58%, 57/98) of the MOOCs considered were offered on the Coursera platform, and 94% (92/98) of all the MOOCs were offered in English. Universities offered 90 MOOCs, and the John Hopkins University offered the largest number of MOOCs (12/90). Only three MOOCs were offered by developing countries (China, West Indies, and Saudi Arabia). The duration of MOOCs varied from 3-20 weeks with an average length of 6.7 weeks. On average, MOOCs expected a participant to work on the material for 4.2 hours a week. Verified certificates were offered by 14 MOOCs, while three others offered other professional recognition. CONCLUSIONS: The review presents evidence to suggest that MOOCs can be used as a way to provide continuous medical education. It also shows the potential of MOOCs as a means of increasing health literacy among the public. PMID- 25123954 TI - Current management of papillary thyroid microcarcinoma in Canada. AB - INTRODUCTION: The detection of papillary thyroid microcarcinoma (PTMC) is on the rise and its optimal management remains controversial. Our aim was to determine the current self-reported management of PTMC amongst Canadian otolaryngologist head and neck surgeons (OHNS) and endocrinologists and to identify factors influencing their management decisions. METHODS: A nine item web-based questionnaire was distributed to Canadian OHNS and endocrinologists. The three main domains were demographics, current management of PTMC scenarios, and factors influencing the decisions. RESULTS: One hundred and thirteen OHNS and endocrinologists completed the survey. Respondents were closely divided between recommending hemithyroidectomy (47%) or total thyroidectomy (43%) for a newly diagnosed PTMC in a low risk patient. Observation was the preferred method for managing PTMC detected incidentally after hemithyroidectomy (76%). Respondents chose more aggressive treatment for male patients compared to female patients. A positive history of thyroid cancer or previous radiation exposure was the most important factor influencing the management of PTMC. CONCLUSION: The current practices of Canadian OHNS and endocrinologist largely coincide with available guidelines. The slight variation in practice might be explained by the opposing evidence supporting different management options. Given the dramatic increase in the incidence of PTMC we suggest future guidelines address the management of PTMC independently. PMID- 25123955 TI - The problem with generic immunosuppressants. PMID- 25123953 TI - Co-inoculation of Glomus intraradices and Trichoderma atroviride acts as a biostimulant to promote growth, yield and nutrient uptake of vegetable crops. AB - BACKGROUND: The application of beneficial microorganisms at transplanting can promote rapid transplant establishment (starter effect) for achieving early and high yields. The aim of this study was to evaluate the biostimulant effects of Glomus intraradices BEG72 (G) and Trichoderma atroviride MUCL 45632 (T) alone or in combination on plant growth parameters, yield, chlorophyll index (SPAD), chlorophyll fluorescence and mineral composition of several vegetable crops. RESULTS: The T. atroviride strain was capable of producing siderophores and auxin like compounds under a wide range of substrate pH conditions (5.5-8.0). The highest shoot, root dry weight, SPAD and chlorophyll fluorescence in lettuce, tomato and zucchini was observed in the G + T combination, followed by a single inoculation of G or T, whereas the lowest values were recorded in the uninoculated plants. Under greenhouse conditions, the shoot dry weight was significantly increased by 167%, 56%, 115%, 68% and 58% in lettuce, melon, pepper, tomato and zucchini, respectively, when supplied with both beneficial microorganisms in comparison with the control. This increase in root and shoot weight was associated with an increased level of nutrient uptake (e.g. P, Mg, Fe, Zn and B). Under open field conditions, the lettuce shoot and root dry weight increased by 61% and 57%, respectively, with biostimulant microorganism application in field conditions. For zucchini, early and total yields were significantly increased by 59% and 15%, respectively, when plants were inoculated with both microorganisms. CONCLUSION: The application of the biostimulant tablet containing both G and T can promote transplant establishment and vegetable crop productivity in a sustainable way. PMID- 25123956 TI - Role for biological meshes for delayed abdominal wall closure after pediatric liver transplantation? PMID- 25123957 TI - Elucidating the nature of transformation in the adolescent transplant patient: time to move from knowledge to action. PMID- 25123958 TI - Factors responsible for incomplete linkage to care after HIV diagnosis: preliminary results from the Test and Keep in Care (TAK) project. AB - OBJECTIVES: Linkage to care after HIV diagnosis remains underinvestigated in Europe, yet delays in linkage to care are an important obstacle to controlling the HIV epidemic. The Test and Keep in Care (TAK) project aims to determine the prevalence of HIV-positive persons who are lost or late to care and factors associated with this. METHODS: Data from community-based voluntary counselling and testing that occurred in 2010-2011 were linked with data from HIV clinics using unique test numbers. Persons not registered in HIV clinics were considered lost to care (LTC). For statistical analysis, nonparametric tests were used for comparison, and a multivariable logistic regression model was developed that included all variables with P<0.1 from the univariable models. RESULTS: A total of 110 persons were diagnosed as HIV-positive: 91% lived in central Poland, 5% were female and 71% were men who have sex with men (MSM). Forty-seven (42%) persons were LTC, seven of whom did not collect their enzyme-linked immunosorbent assay (ELISA) test result. Of those who registered, 75% registered within 1 month from HIV diagnosis, and 54% were late presenters. LTC individuals were more likely to have heterosexual or bisexual orientation, to have >20 sexual partners, to not be in a relationship with an HIV-positive partner, to not use condoms, and to be taking their first HIV test. In a logistic regression model, after adjusting for these factors, using condoms in a stable relationship decreased the odds of LTC by 72% (odds ratio 0.28; confidence interval 0.11-0.67). CONCLUSIONS: Integration into care after HIV diagnosis requires improvement. Our results suggest that broadening awareness and counselling about sexual risks may have a positive impact. PMID- 25123959 TI - Polycystin-1 and polycystin-2 are involved in the acquisition of aggressive phenotypes in colorectal cancer. AB - The polycystins PC1 and PC2 are emerging as major players in mechanotransduction, a process that influences all steps of the invasion/metastasis cascade. We hypothesized that PC1 and PC2 facilitate cancer aggressiveness. Immunoblotting, RT-PCR, semi-quantitative and quantitative real-time PCR and FACS analyses were employed to investigate the effect of polycystin overexpression in colorectal cancer (CRC) cells. The impact of PC1 inhibition on cancer-cell proliferation was evaluated through an MTT assay. In vitro data were analyzed by Student's t-test. HT29 human xenografts were treated with anti-PC1 (extracellular domain) inhibitory antibody and analyzed via immunohistochemistry to determine the in vivo role of PC1 in CRC. Clinical significance was assessed by examining PC1 and PC2 protein expression in CRC patients (immunohistochemistry). In vivo and clinical data were analyzed by non-parametric tests, Kaplan-Meier curves, log rank test and Cox model. All statistical tests were two-sided. PC1 overexpression promotes epithelial-to-mesenchymal transition (EMT) in HCT116 cells, while PC2 overexpression results in upregulation of the mTOR pathway in SW480 cells. PC1 inhibition causes reduced cell proliferation in CRC cells inducing tumor necrosis and suppressing EMT in HT29 tumor xenografts. In clinical study, PC1 and PC2 overexpression associates with adverse pathological parameters, including invasiveness and mucinous carcinomas. Moreover, PC1 overexpression appears as an independent prognostic factor of reduced recurrence-free survival (HR = 1.016, p = 0.03) and lowers overall survival probability, while aberrant PC2 expression predicts poor overall survival (p = 0.0468). These results support, for the first time, a direct link between mechanosensing polycystins (PC1 and PC2) and CRC progression. PMID- 25123960 TI - FeCr2S4 in magnetic fields: possible evidence for a multiferroic ground state. AB - We report on neutron diffraction, thermal expansion, magnetostriction, dielectric, and specific heat measurements on polycrystalline FeCr2S4 in external magnetic fields. The ferrimagnetic ordering temperatures TC ~ 170 K and the transition at TOO ~ 10 K, which has been associated with orbital ordering, are only weakly shifted in magnetic fields up to 9 T. The cubic lattice parameter is found to decrease when entering the state below TOO. The magnetic moments of the Cr- and Fe-ions are reduced from the spin-only values throughout the magnetically ordered regime, but approach the spin-only values for fields >5.5 T. Thermal expansion in magnetic fields and magnetostriction experiments indicate a contraction of the sample below about 60 K. Below TOO this contraction is followed by a moderate expansion of the sample for fields larger than ~4.5 T. The transition at TOO is accompanied by an anomaly in the dielectric constant. The dielectric constant depends on both the strength and orientation of the external magnetic field with respect to the applied electric field for T < TOO. A linear correlation of the magnetic-field-induced change of the dielectric constant and the magnetic-field dependent magnetization is observed. This behaviour is consistent with the existence of a ferroelectric polarization and a multiferroic ground state below 10 K. PMID- 25123961 TI - N-heterocyclic carbene, high oxidation state molybdenum alkylidene complexes: functional-group-tolerant cationic metathesis catalysts. AB - We synthesized the first N-heterocyclic carbene (NHC) complexes of Schrock's molybdenum imido alkylidene bis(triflate) complexes. Unlike existing bis(triflate) complexes, the novel 16-electron complexes represent metathesis active, functional-group-tolerant catalysts. Single-crystal X-ray structures of two representatives of this novel class of Schrock catalysts are presented and reactivity is discussed in view of their structural peculiarities. In the presence of monomer (substrate), these catalysts form cationic species and can be employed in ring-closing metathesis (RCM), ring-opening metathesis polymerization (ROMP), as well as in the cyclopolymerization of alpha,omega-diynes. Monomers containing functional groups, which are not tolerated by the existing variations of Schrock's catalyst, e.g., sec-amine, hydroxy, and carboxylic acid moieties, can be used. These catalysts therefore hold great promise in both organic and polymer chemistry, where they allow for the use of protic monomers. PMID- 25123962 TI - Safe management of chronic pain in pregnancy in an era of opioid misuse and abuse. AB - Safe and effective management of chronic pain in pregnancy is challenging. Use of over-the-counter analgesics, opioids, opioid substitution therapies, complementary and alternative therapies, antidepressants, and anxiolytics each have benefits and risks for the mother and neonate that must be considered. Because of their potency, opioids are often used despite associated risks for adverse effects, abuse, diversion, and addiction. Development of a pain management protocol for the counsel and care of pregnant women with pain is necessary. PMID- 25123963 TI - Molecular profiling in fresh tissue with high tumor cell content promotes enrichment for aggressive adenocarcinomas in cervix. AB - Many emerging tools for comprehensive molecular profiling of malignant lesions demand fresh frozen tissue with a high tumor purity. Often, a tumor epithelial content of at least 80% is recommended. This approach may lead to a systematic bias, and therefore we explore if this introduces a selection of cases with a certain phenotype in cervical cancer. Clinicopathologic data for a population based cohort of 328 patients have been studied. Fresh frozen tumor specimens were available for 151 of these patients and investigated for epithelial tumor cell portion in hematoxylin-stained frozen sections by light microscopy. The estimated tumor purity in the samples was compared with FIGO stage, histopathologic characteristics and survival. High tumor purity was significantly more often found in squamous cell carcinoma (SCC) compared to adenocarcinoma (AC) (P=0.03). For the subgroup of AC (n=40), there was a significant association between high tumor purity in the fresh frozen samples and later occurrence of recurrent disease (P=0.04). In SCC, no significant associations between tumor purity and disease stage, grade or outcome were found. Apparently in line with this, grade was found to influence prognosis in AC, but not in SCC. Our findings suggest that selection of samples based on high tumor purity in fresh frozen tissue may introduce a selection bias toward aggressive disease for the subgroup of AC, but not for SCC of the cervix. Thus, the prevalence of potential molecular biomarkers identified in AC in particular should be validated in a population-based setting to further explore clinical relevance. Also, molecular biomarkers only prevalent in subgroups with low tumor purity may go undetected in sample collections enriched for high tumor purity. PMID- 25123965 TI - Complete Genome Sequence of the Siphoviral Bacteriophage YMC/09/04/R1988 MRSA BP: A lytic phage from a methicillin-resistant Staphylococcus aureus isolate. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing cause of serious infection, both in the community and hospital settings. Despite sophisticated strategies and efforts, the antibiotic options for treating MRSA infection have been narrowed due to the limited number of newly developed antimicrobials. Herein, we analyze the completely sequenced genome of a novel virulent phage YMC/09/04/R1988 MRSA BP as a potential alternative anti-MRSA agent, which lysed clinical isolates from a patient admitted to the hospital due to hip disarticulation. The phage contains a linear double-stranded DNA genome of 44,459 bp in length, with 33.37% GC content, 62 predicted open reading frames (ORFs), and annotated functions of only 23 ORFs that are associated with structural assembly, host lysis, DNA replication, and modification. It showed a broad host range (17 of 30 strains) against MRSA strains in clinical isolates. This article is protected by copyright. All rights reserved. PMID- 25123964 TI - Limited reliability of five non-invasive biomarkers in predicting hepatic fibrosis in chronic HCV mono-infected patients opposed to METAVIR scoring. AB - BACKGROUND: Liver biopsy is gold standard for fibrosis assessment in hepatitis C virus (HCV) infection but its limitations led to the identification of non invasive biomarkers. This study assesses the reliability of five biomarkers in estimating the stage of liver fibrosis/cirrhosis in chronic HCV patients versus METAVIR scoring. METHODS: One hundred HCV monoinfected patients who underwent liver biopsy and blood sampling were included. Liver fibrosis was staged (F0-4) and required laboratory tests were performed. AAR, API, APRI, FIB-4 and Pohl score were calculated and their receiver operating curves (ROCs), sensitivities, specificities, predictive values and accuracies were evaluated. RESULTS: There were 27, 44, and 29 patients at F0-F1, F2-F3, and F4 groups. Significant statistical differences were found regarding AST, vireamia, platelet count, prothrombin time and all biomarkers. From ROCs only Pohl score predicted significant fibrosis and cirrhosis but with low accuracy. AAR, API and APRI showed moderate performance at low cut-offs, but had limited predictive values or accuracies at higher cut-offs. FIB-4 was the least accurate test. The diagnostic reliability of these biomarkers was limited to patients with suspected insignificant fibrosis. CONCLUSIONS: This study verified the limited reliability for AAR, API, APRI, FIB-4 and Pohl score in estimating the stage of hepatic fibrosis in HCV infected patients opposed to METAVIR scoring. PMID- 25123966 TI - Confounder selection via penalized credible regions. AB - When estimating the effect of an exposure or treatment on an outcome it is important to select the proper subset of confounding variables to include in the model. Including too many covariates increases mean square error on the effect of interest while not including confounding variables biases the exposure effect estimate. We propose a decision-theoretic approach to confounder selection and effect estimation. We first estimate the full standard Bayesian regression model and then post-process the posterior distribution with a loss function that penalizes models omitting important confounders. Our method can be fit easily with existing software and in many situations without the use of Markov chain Monte Carlo methods, resulting in computation on the order of the least squares solution. We prove that the proposed estimator has attractive asymptotic properties. In a simulation study we show that our method outperforms existing methods. We demonstrate our method by estimating the effect of fine particulate matter (PM2.5) exposure on birth weight in Mecklenburg County, North Carolina. PMID- 25123967 TI - Dry-processable carbon nanotubes for functional devices and composites. AB - Assembly of carbon nanotubes (CNTs) in effective and productive ways is of vital importance to their application. Recent progress in synthesis of CNTs has inspired new strategies for utilizing the unique physiochemical properties of CNTs in macroscale materials and devices. Assembling CNTs by dry processes (e.g., directly collecting CNTs in the form of freestanding films followed by pressing, stretching, and multilayer stacking instead of dispersing them in solution) not only considerably simplifies the processes but also avoids structural damage to the CNTs. Various dry-processable CNTs are reviewed, focusing on their synthesis, properties, and applications. The synthesis techniques are organized in terms of aggregative morphologies and microstructure control of CNTs. Important applications such as functional thin-film devices, strong CNT films, and composites are included. The opportunities and challenges in the synthesis techniques and fabrication of advanced composites and devices are discussed. PMID- 25123969 TI - [Update pediatric orthopedics]. PMID- 25123970 TI - [Orthopedics update: tumor orthopedics]. PMID- 25123968 TI - The validity of a behavioural multiple-mini-interview within an assessment centre for selection into specialty training. AB - BACKGROUND: Entry into specialty training was determined by a National Assessment Centre (NAC) approach using a combination of a behavioural Multiple-Mini Interview (MMI) and a written Situational Judgement Test (SJT). We wanted to know if interviewers could make reliable and valid decisions about the non-cognitive characteristics of candidates with the purpose of selecting them into general practice specialty training using the MMI. Second, we explored the concurrent validity of the MMI with the SJT. METHODS: A variance components analysis estimated the reliability and sources of measurement error. Further modelling estimated the optimal configurations for future MMI iterations. We calculated the relationship of the MMI with the SJT. RESULTS: Data were available from 1382 candidates, 254 interviewers, six MMI questions, five alternate forms of a 50 item SJT, and 11 assessment centres. For a single MMI question and one assessor, 28% of the variance between scores was due to candidate-to-candidate variation. Interviewer subjectivity, in particular the varying views that interviewer had for particular candidates accounted for 40% of the variance in scores. The generalisability co-efficient for a six question MMI was 0.7; to achieve 0.8 would require ten questions. A disattenuated correlation with the SJT (r = 0.35), and in particular a raw score correlation with the subdomain related to clinical knowledge (r = 0.25) demonstrated evidence for construct and concurrent validity. Less than two per cent of candidates would have failed the MMI. CONCLUSION: The MMI is a moderately reliable method of assessment in the context of a National Assessment Centre approach. The largest source of error relates to aspects of interviewer subjectivity, suggesting enhanced interviewer training would be beneficial. MMIs need to be sufficiently long for precise comparison for ranking purposes. In order to justify long term sustainable use of the MMI in a postgraduate assessment centre approach, more theoretical work is required to understand how written and performance based test of non-cognitive attributes can be combined, in a way that achieves acceptable generalizability, and has validity. PMID- 25123971 TI - [springermedizin.de -- the editor recommends]. PMID- 25123972 TI - Lineage-specific evolution of cnidarian Wnt ligands. AB - We have studied the evolution of Wnt genes in cnidarians and the expression pattern of all Wnt ligands in the hydrozoan Hydractinia echinata. Current views favor a scenario in which 12 Wnt sub-families were jointly inherited by cnidarians and bilaterians from their last common ancestor. Our phylogenetic analyses clustered all medusozoan genes in distinct, well-supported clades, but many orthologous relationships between medusozoan Wnts and anthozoan and bilaterian Wnt genes were poorly supported. Only seven anthozoan genes, Wnt2, Wnt4, Wnt5, Wnt6, Wnt 10, Wnt11, and Wnt16 were recovered with strong support with bilaterian genes and of those, only the Wnt2, Wnt5, Wnt11, and Wnt16 clades also included medusozoan genes. Although medusozoan Wnt8 genes clustered with anthozoan and bilaterian genes, this was not well supported. In situ hybridization studies revealed poor conservation of expression patterns of putative Wnt orthologs within Cnidaria. In polyps, only Wnt1, Wnt3, and Wnt7 were expressed at the same position in the studied cnidarian models Hydra, Hydractinia, and Nematostella. Different expression patterns are consistent with divergent functions. Our data do not fully support previous assertions regarding Wnt gene homology, and suggest a more complex history of Wnt family genes than previously suggested. This includes high rates of sequence divergence and lineage specific duplications of Wnt genes within medusozoans, followed by functional divergence over evolutionary time scales. PMID- 25123973 TI - Association of creative achievement with cognitive flexibility by a combined voxel-based morphometry and resting-state functional connectivity study. AB - Although researchers generally concur that creativity involves the production of novel and useful products, the neural basis of creativity remains elusive due to the complexity of the cognitive processes involved. Recent studies have shown that highly creative individuals displayed more cognitive flexibility. However, direct evidence supporting the relationship between creativity and cognitive flexibility has rarely been investigated using both structural and functional neuroimaging techniques. We used a combined voxel-based morphometry and resting state functional connectivity (rsFC) analysis to investigate the relationship between individual creativity ability assessed by the creative achievement questionnaire (CAQ), and regional gray matter volume (GMV), as well as intrinsic functional connectivity. Results showed that CAQ scores negatively correlated with GMV in the rostral anterior cingulate cortex (ACC) and the bilateral dorsal ACC (dACC) extending to supplementary motor area, but positively correlated with GMV in the bilateral superior frontal gyrus and ventral medial prefrontal cortex (vmPFC). Further functional connectivity analysis revealed that higher creative achievement was inversely associated with the strength of rsFC between the dACC and medial superior frontal gyrus (mSFG), right middle frontal gyrus, and left orbito-frontal insula. Moreover, the association between the dACC-mSFG connectivity and CAQ scores was mediated by cognitive flexibility, assessed by a task-switching paradigm. These findings indicate that individual differences in creative achievement are associated with both brain structure and corresponding intrinsic functional connectivity involved in cognitive flexibility and deliberate creative processing. Furthermore, dACC-mSFG connectivity may affect creative achievement through its impact on cognitive flexibility. PMID- 25123974 TI - Repetition probability effects for inverted faces. AB - It has been shown, that the repetition related reduction of the blood-oxygen level dependent (BOLD) signal is modulated by the probability of repetitions (P(rep)) for faces (Summerfield et al., 2008), providing support for the predictive coding (PC) model of visual perception (Rao and Ballard, 1999). However, the stage of face processing where repetition suppression (RS) is modulated by P(rep) is still unclear. Face inversion is known to interrupt higher level configural/holistic face processing steps and if modulation of RS by P(rep) takes place at these stages of face processing, P(rep) effects are expected to be reduced for inverted when compared to upright faces. Therefore, here we aimed at investigating whether P(rep) effects on RS observed for face stimuli originate at the higher-level configural/holistic stages of face processing by comparing these effects for upright and inverted faces. Similarly to previous studies, we manipulated P(rep) for pairs of stimuli in individual blocks of fMRI recordings. This manipulation significantly influenced repetition suppression in the posterior FFA, the OFA and the LO, independently of stimulus orientation. Our results thus reveal that RS in the ventral visual stream is modulated by P(rep) even in the case of face inversion and hence strongly compromised configural/holistic face processing. An additional whole-brain analysis could not identify any areas where the modulatory effect of probability was orientation specific either. These findings imply that P(rep) effects on RS might originate from the earlier stages of face processing. PMID- 25123975 TI - Comparison of long-term outcomes following traumatic injury: what is the unique experience for those with brain injury compared with orthopaedic injury? AB - OBJECTIVE: Whilst it has been well-demonstrated that traumatic brain injury (TBI) results in long-term cognitive, behavioural and emotional difficulties, less is understood about how these outcomes differ from those following traumatic orthopaedic injury (TOI). The aim of this study was to compare self-reported outcomes at 5-10 years post-injury for those with TBI, TOI, and uninjured controls. It was hypothesised that participants with TBI would have greater cognitive difficulties; participants with TOI and TBI would have similar functional and physical outcomes, both being poorer than controls; and participants with TBI would have poorer psychosocial outcomes than those with TOI. PARTICIPANTS AND METHODS: Eighty-eight individuals with complicated mild to severe TBI and 96 with TOI recruited during inpatient rehabilitation were followed up 5-10 years post-injury, together with 48 controls followed over a similar period. Self-report measures of global functioning (GOS-E), quality of life (SF-36), psychological wellbeing (SCL-90-R, HADS, PCL-S), psychosocial difficulties (SIP), cognitive difficulties (SF-36 COG), pain (BPI), and fatigue (FSS) were administered. RESULTS: Outcomes for individuals with TBI and TOI differed significantly from controls, with poorer global functioning, and greater psychological distress and interference from pain. Only participants with TBI reported greater cognitive difficulties and anxiety than controls, and were less likely to be employed or in a relationship. Participants with TBI reported greater anxiety, PTSD, psychological distress and psychosocial difficulties than those with TOI. CONCLUSIONS: Both TOI and TBI cause long-term disability, interference from pain, and psychological distress. However, cognitive impairments, unemployment, lack of long-term relationships, anxiety and PTSD are more substantial long-term problems following TBI. Findings from this study have implications for managing risks associated with these injury groups and tailoring rehabilitation to improve long-term outcomes. PMID- 25123976 TI - Central 22q11.2 deletions. AB - 22q11.2 deletion syndrome is one of the most common microdeletion syndromes. Most patients have a deletion resulting from a recombination of low copy repeat blocks LCR22-A and LCR22-D. Loss of the TBX1 gene is considered the most important cause of the phenotype. A limited number of patients with smaller, overlapping deletions distal to the TBX1 locus have been described in the literature. In these patients, the CRKL gene is deleted. Haploinsufficiency of this gene has also been implicated in the pathogenesis of 22q11.2 deletion syndrome. To distinguish these deletions (comprising the LCR22-B to LCR22-D region) from the more distal 22q11.2 deletions (located beyond LCR22-D), we propose the term "central 22q11.2 deletions". In the present study we report on 27 new patients with such a deletion. Together with information on previously published cases, we review the clinical findings of 52 patients. The prevalence of congenital heart anomalies and the frequency of de novo deletions in patients with a central deletion are substantially lower than in patients with a common or distal 22q11.2 deletion. Renal and urinary tract malformations, developmental delays, cognitive impairments and behavioral problems seem to be equally frequent as in patients with a common deletion. None of the patients had a cleft palate. Patients with a deletion that also encompassed the MAPK1 gene, located just distal to LCR22-D, have a different and more severe phenotype, characterized by a higher prevalence of congenital heart anomalies, growth restriction and microcephaly. Our results further elucidate genotype-phenotype correlations in 22q11.2 deletion syndrome spectrum. PMID- 25123977 TI - Potential role of cinacalcet hydrochloride in sporadic primary hyperparathyroidism without surgery indication. PMID- 25123978 TI - Enzalutamide in European and North American men participating in the AFFIRM trial. AB - OBJECTIVE: To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311). PATIENTS AND METHODS: Phase III, double-blind, placebo controlled, multinational AFFIRM trial in men with metastatic castration resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly assigned in a 2:1 ratio to receive oral enzalutamide 160 mg/day or placebo. The primary end point was overall survival (OS) in a post hoc analysis. RESULTS: Enzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263 enzalutamide-treated, 0.38%) had seizures. The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry. CONCLUSION: This post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA- and EU-treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions. PMID- 25123980 TI - Cadmium and lead in chocolates commercialized in Brazil. AB - Cadmium (Cd) and lead (Pb) concentrations and their relationship to the cocoa content of chocolates commercialized in Brazil were evaluated by graphite furnace atomic absorption spectrometry (GF AAS) after microwave-assisted acid digestion. Several chemical modifiers were tested during method development, and analytical parameters, including the limits of detection and quantification as well as the accuracy and precision of the overall procedure, were assessed. The study examined 30 chocolate samples, and the concentrations of Cd and Pb were in the range of <1.7-107.6 and <21-138.4 ng/g, respectively. The results indicated that dark chocolates have higher concentrations of Cd and Pb than milk and white chocolates. Furthermore, samples with five different cocoa contents (ranging from 34 to 85%) from the same brand were analyzed, and linear correlations between the cocoa content and the concentrations of Cd (R(2) = 0.907) and Pb (R(2) = 0.955) were observed. The results showed that chocolate might be a significant source of Cd and Pb ingestion, particularly for children. PMID- 25123979 TI - Comparison of ARIMA and Random Forest time series models for prediction of avian influenza H5N1 outbreaks. AB - BACKGROUND: Time series models can play an important role in disease prediction. Incidence data can be used to predict the future occurrence of disease events. Developments in modeling approaches provide an opportunity to compare different time series models for predictive power. RESULTS: We applied ARIMA and Random Forest time series models to incidence data of outbreaks of highly pathogenic avian influenza (H5N1) in Egypt, available through the online EMPRES-I system. We found that the Random Forest model outperformed the ARIMA model in predictive ability. Furthermore, we found that the Random Forest model is effective for predicting outbreaks of H5N1 in Egypt. CONCLUSIONS: Random Forest time series modeling provides enhanced predictive ability over existing time series models for the prediction of infectious disease outbreaks. This result, along with those showing the concordance between bird and human outbreaks (Rabinowitz et al. 2012), provides a new approach to predicting these dangerous outbreaks in bird populations based on existing, freely available data. Our analysis uncovers the time-series structure of outbreak severity for highly pathogenic avain influenza (H5N1) in Egypt. PMID- 25123981 TI - Increased ethanol production from sweet sorghum juice concentrated by a membrane separation process. AB - The aim of this investigation was to attain high ethanol concentration by concentrating sweet sorghum juice using a two-step membrane separation process. Ultrafiltration permeation of the juice was used to remove residues, followed by nanofiltration concentration to increase the sugar concentration. The concentrated juice containing 180.0 g L(-1) sucrose, 59.3 g L(-1) glucose and 49.3 g L(-1) fructose supplemented with nitrogen sources (10 and 20 g L(-1) of yeast extract and polypeptone, respectively) was fermented by Saccharomyces cerevisiae BY4741 to produce 133.5 g L(-1) of ethanol (87.6% of theoretical yield) after 48 h fermentation. Importantly, the addition of lower concentrations of exogenous nitrogen sources (3 and 6 g L(-1) of yeast extract and polypeptone, respectively) or no exogenous nitrogen sources resulted in the production of 131.4 and 132.8 g L(-1) of ethanol (84.8% and 86.0% of theoretical yield), respectively, after 48 h fermentation. PMID- 25123982 TI - Physical pretreatments of wastewater algae to reduce ash content and improve thermal decomposition characteristics. AB - Previous study showed high ash content in wastewater algae (WA) has a negative effect on bio-crude oil formation in hydrothermal liquefaction (HTL). This study explored the effect of different pretreatments on ash reduction and the thermal decomposition of WA. Single-stage (e.g. centrifugation) and two-stage pretreatments (e.g. centrifugation followed by ultrasonication, C+U) were used. The apparent activation energy of the thermal decomposition (E(a)) of pretreated algae was determined. HTL was conducted to study how different pretreatments may impact on bio-crude oil formation. Compared to untreated samples, the ash content of algae with centrifugation was reduced from 28.6% to 18.6%. With C+U pretreatments, E(a) was decreased from 50.2 kJ/mol to 35.9 kJ/mol and the bio crude oil yield was increased from 30% to 55%. These results demonstrate that pretreatments of C+U can improve the thermal decomposition behavior of WA and enhance the bio-crude oil conversion efficiency. PMID- 25123984 TI - Self-powered energy fiber: energy conversion in the sheath and storage in the core. AB - A high-performance, self-powered, elastic energy fiber is developed that consists of an energy conversion sheath and an energy storage core. The coaxial structure and the aligned nanostructures at the electrode interface enable a high total energy-conversion and energy-storage performance that is maintained under bending and after stretching. PMID- 25123983 TI - Influence of health-related quality of life on health service utilization in Chinese rural-to-urban female migrant workers. AB - BACKGROUND: Rural-to-urban migrant workers have been increasing rapidly in China over recent decades. Health related quality of life (HRQOL) may affect health service utilization. There is a lack of data on HRQOL in relation to health service utilization in Chinese rural-to-urban migrant workers. This study was aimed to explore the influence of HRQOL on health service utilization in Chinese rural-to-urban female migrant workers. METHODS: This was a cross-sectional survey of 1,438 female rural-to-urban migrant workers in Shenzhen-Dongguan economic zone, China in 2013. HRQOL was assessed by the 36-items Health Survey Short Form (SF-36). Health service utilization was measured by any physician visit over the recent two weeks and any hospitalization over the last 1-year (annual hospitalization). Clustered logistic regression was used to analyze the influence of HRQOL on health service utilization. RESULTS: Lower scores in three HRQOL domains (bodily pain, general health, role physical) were associated with more frequent health service utilization in female rural-to-urban migrant workers. Bodily pain and general health were associated with an independent influence of 15.6% on the risk of recent two-week physician visit, while role physical and general health were associated with an independent influence of 21.2% on the risk of annual hospitalization. The independent influence of HRQOL on health service utilization was smaller than that of socio-demographic and health-related variables. CONCLUSIONS: HRQOL may have a modest influence on health service utilization in Chinese rural-to-urban female migrant workers - an underprivileged population in urban China. PMID- 25123985 TI - Rates and risk factors associated with depressive symptoms during pregnancy and with postpartum onset. AB - The objectives of this study were to evaluate the prevalence of depressive symptoms in the third trimester of pregnancy and at 3 months postpartum and to prospectively identify risk factors associated with elevated depressive symptoms during pregnancy and with postpartum onset. About 364 women attending antenatal clinics or at the time of their ultrasound were recruited and completed questionnaires in pregnancy and 226 returned their questionnaires at 3 months postpartum. Depressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS; score of >= 10). The rate of depressed mood during pregnancy was 28.3% and 16.4% at 3 months postpartum. Among women with postpartum depressed mood, 6.6% were new postpartum cases. In the present study, belonging to a non Caucasian ethnic group, a history of emotional problems (e.g. anxiety and depression) or of sexual abuse, comorbid anxiety, higher anxiety sensitivity and having experienced stressful events were associated with elevated depressed mood during pregnancy. Four risk factors emerged as predictors of new onset elevated depressed mood at 3 months postpartum: higher depressive symptomatology during pregnancy, a history of emotional problems, lower social support during pregnancy and a delivery that was more difficult than expected. The importance of identifying women at risk of depressed mood early in pregnancy and clinical implications are discussed. PMID- 25123986 TI - Reliability and validity of three shortened versions of the State Anxiety Inventory scale during the perinatal period. AB - The screening for anxiety in obstetric settings has been challenging due to time and knowledge constraints. Brief, valid, and reliable instruments can provide health care professionals with a quick and easy method to assess anxiety. Three six-item forms of the State Anxiety Inventory scale have been constructed. The purpose of this study was to evaluate and compare the psychometric properties of these short versions in the perinatal period. Data were drawn from a longitudinal pregnancy cohort in Alberta, Canada. Internal consistency of the shortened versions was assessed. Confirmatory factor analysis was conducted to estimate and compare indicators of fit during pregnancy and at 4 and 12 months postpartum. All shortened scales demonstrated high internal consistency and reliability, with alphas ranging from 0.81 to 0.85. All fit indices were greater than 0.93, implying a good fit between each model and our data. In the model comparisons, the Marteau and Bekker scale provided a more robust fit to data obtained during pregnancy and the early postpartum period. At 12 months postpartum, the Chlan et al. form demonstrated the best fit of the three versions. The shortened scales appear to have acceptable psychometric properties. Brief scales have the potential to provide an economical means of assessing perinatal anxiety and can be considered as equivalent alternatives to the full-scale version. PMID- 25123988 TI - Effect of deodorant and antiperspirant use and presence or absence of axillary hair on absorption of testosterone 2% solution applied to men's axillae. AB - INTRODUCTION: Testosterone 2% solution is applied to axillae and is indicated for testosterone replacement therapy in males deficient in endogenous testosterone. AIM: This open-label crossover study evaluated the effect of deodorant/antiperspirant use and presence or absence of axillary hair on absorption of testosterone solution. METHODS: Healthy males (N = 30; >=50 years of age with baseline testosterone <400 ng/dL) were randomized to one of four treatment sequences involving six treatments. Each treatment consisted of one 1.5 mL dose of testosterone 2% solution (30 mg of testosterone) applied to each axilla. Axillae were unshaved or shaved, and were untreated or pretreated with deodorant/antiperspirant. MAIN OUTCOME MEASURES: Blood samples were taken over 72 hours after each dose for measuring serum testosterone concentrations. RESULTS: Profiles of mean testosterone concentrations were similar across treatments. For all treatments, area under the concentration-time curve through 24 hours (AUC[0 24] ) and 72 hours (AUC[0-72] ), and maximum total testosterone concentration (Cmax ) were similar except for 15% lower Cmax when treatment was applied after deodorant/antiperspirant to shaved vs. unshaved axillae (least squares mean, 531 ng/dL vs. 626 ng/dL, respectively; P = 0.011). This difference is not considered clinically significant. The 95% confidence intervals for AUC(0-24) , AUC(0-72) , and Cmax fell within the traditional bioequivalence limits of 0.8 to 1.25. Incidence of treatment-emergent adverse events (TEAEs) was low (<15%) in each treatment arm, and most TEAEs were mild. CONCLUSIONS: Absorption of testosterone 2% solution was unaffected by use of deodorant/antiperspirant or by the presence or absence of axillary hair. Testosterone solution was generally well tolerated. PMID- 25123987 TI - Speech perception and production by sequential bilingual children: a longitudinal study of voice onset time acquisition. AB - The majority of bilingual speech research has focused on simultaneous bilinguals. Yet, in immigrant communities, children are often initially exposed to their family language (L1), before becoming gradually immersed in the host country's language (L2). This is typically referred to as sequential bilingualism. Using a longitudinal design, this study explored the perception and production of the English voicing contrast in 55 children (40 Sylheti-English sequential bilinguals and 15 English monolinguals). Children were tested twice: when they were in nursery (52-month-olds) and 1 year later. Sequential bilinguals' perception and production of English plosives were initially driven by their experience with their L1, but after starting school, changed to match that of their monolingual peers. PMID- 25123989 TI - The impact of an antimicrobial stewardship programme on the use of antimicrobials and the evolution of drug resistance. AB - Misuse of antibiotics can provoke increased bacterial resistance. There are no immediate prospects of any new broad-spectrum antibiotics, especially any with activity against enterobacteria, coming onto the market. Therefore, programmes should be implemented to optimise antimicrobial therapy. In a quasi-experimental study, the results for the pre-intervention year were compared with those for the 3 years following the application of an antimicrobial stewardship programme. We describe 862 interventions carried out as part of the stewardship programme at the Hospital Costa del Sol from 2009 to 2011. We examined the compliance of the empirical antimicrobial treatment with the programme recommendations and the treatment optimisation achieved by reducing the antibiotic spectrum and adjusting the dose, dosing interval and duration of treatment. In addition, we analysed the evolution of the sensitivity profile of the principal microorganisms and the financial savings achieved. 93 % of the treatment recommendations were accepted. The treatment actions taken were to corroborate the empirical treatment (46 % in 2009 and 31 % in 2011) and to reduce the antimicrobial spectrum taking into account the antibiogram results (37 % in 2009 and 58 % in 2011). The main drugs assessed were imipenem/meropenem, used in 38.6 % of the cases, and cefepime (20.1 %). The sensitivity profile of imipenem against Pseudomonas aeruginosa increased by 10 % in 2011. Savings in annual drug spending (direct costs) of 30,000 Euros were obtained. Stewardship programmes are useful tools for optimising antimicrobial therapy. They may contribute to preventing increased bacterial resistance and to reducing the long-term financial cost of antibiotic treatment. PMID- 25123990 TI - Design of a metal-promoted oxide catalyst for the selective synthesis of butadiene from ethanol. AB - The synthesis of buta-1,3-diene from ethanol has been studied over metal containing (M=Ag, Cu, Ni) oxide catalysts (MO(x)=MgO, ZrO2, Nb2O5, TiO2, Al2O3) supported on silica. Kinetic study of a wide range of ethanol conversions (2-90%) allowed the main reaction pathways leading to butadiene and byproducts to be determined. The key reaction steps of butadiene synthesis were found to involve ethanol dehydrogenation, acetaldehyde condensation, and the reduction of crotonaldehyde with ethanol into crotyl alcohol. Catalyst design included the selection of active components for each key reaction step and merging of these components into multifunctional catalysts and adjusting the catalyst functions to achieve the highest selectivity. The best catalytic performance was achieved over the Ag/ZrO2/SiO2 catalyst, which showed the highest selectivity towards butadiene (74 mol%). PMID- 25123991 TI - Investigation of the immunogenicity of different types of aggregates of a murine monoclonal antibody in mice. AB - PURPOSE: The potential contribution of protein aggregates to the unwanted immunogenicity of protein pharmaceuticals is a major concern. In the present study a murine monoclonal antibody was utilized to study the immunogenicity of different types of aggregates in mice. Samples containing defined types of aggregates were prepared by processes such as stirring, agitation, exposure to ultraviolet (UV) light and exposure to elevated temperatures. METHODS: Aggregates were analyzed by size-exclusion chromatography, light obscuration, turbidimetry, infrared (IR) spectroscopy and UV spectroscopy. Samples were separated into fractions based on aggregate size by asymmetrical flow field-flow fractionation or by centrifugation. Samples containing different types and sizes of aggregates were subsequently administered to C57BL/6 J and BALB/c mice, and serum was analyzed for the presence of anti-IgG1, anti-IgG2a, anti-IgG2b and anti-IgG3 antibodies. In addition, the pharmacokinetic profile of the murine antibody was investigated. RESULTS: In this study, samples containing high numbers of different types of aggregates were administered in order to challenge the in vivo system. The magnitude of immune response depends on the nature of the aggregates. The most immunogenic aggregates were of relatively large and insoluble nature, with perturbed, non-native structures. CONCLUSION: This study shows that not all protein drug aggregates are equally immunogenic. PMID- 25123993 TI - Smoking, behavioral factors and familial environment: a population based study with Brazilian adolescents. AB - OBJECTIVE: The aim of the present study was to assess the association between smoking and both behavioral and environmental factors among adolescents in the public school system in the city of Campina Grande (northeastern Brazil). METHODS: An analytical cross-sectional study was carried out involving 574 schoolchildren between 10 and 19 years, with the use of a structured questionnaire addressing behavioral factors, environmental factors and smoking. The chi-squared test and Fisher's exact test were used for the statistical analysis (5 % level of significance). RESULTS: The prevalence of smoking was de 3.3 %. The lowest age regarding the use of tobacco for the first time was eight years and the age group with the greatest frequency of initiation into this habit was 11 to 14 years (44.3 %). A total of 84.3 % of tobacco users smoked between one and 10 cigarettes per day. Smoking was associated with delays in schooling (p=0.047), gender (p=0.016), alcohol use and frequency of alcohol use (p<0.001) and the relationship with one's father (p=0.014) and mother (p=0.004). CONCLUSIONS: Despite the low prevalence, an early initiation into smoking was found, suggesting that educational campaigns should be directed at earlier ages. Alcohol use stood out among the variables studied, suggesting that smoking is influenced by both the use and intensity of this substance. PMID- 25123992 TI - [Labour factors associated with post-traumatic stress in uniformed workers in Medellin]. AB - OBJECTIVE: Determining the labor factors associated with post-traumatic stress in uniformed workers in Medellin. METHOD: A cross-sectional study was made of 124 uniformed workers aged 20 to 48 years-old. A survey was made using an adults' post-traumatic stress instrument which had been validated in Medellin. Statistical analysis was carried out. RESULTS: Post-traumatic stress disorder risk prevalence was 52.2 %. Multivariate analysis showed that the highest risk situations were those related to previous mental health diagnosis (PR=7.67), working schedule (4.24), violent episodes (PR=3.59) and community relationships (PR=2.73). CONCLUSIONS: A person's current labor situation seemed to be a risk factor for developing post-traumatic stress in the target population. PMID- 25123994 TI - [The 20th century legal framework regarding risk at work and occupational health in Colombia]. AB - OBJECTIVE: Analyzing the 20th century Colombian legal framework from the point of view of labor law, social security and public health for identifying concepts regarding occupational health and professional risk and trying to establish convergence and differences between such foci and whether they fulfilled a complementary view. METHOD: This work involved documentary research by means of thematic categorical analysis of the laws and statutes promulgated in 20th century Colombia, considering the main element or entity which should have regulated that related to professional risk or occupational health. RESULTS: The development of the 20th century Colombian legal framework regarding health at work was periodized, revealing the predominance of a view of social law focused on protecting dependent workers' work-related risks, as part of a tendency extending to the Colombian Sistema General de Riesgos Laborales. CONCLUSIONS: The proposed stages used for organizing the legal framework concerning social security regarding professional risk and occupational health facilitated some important elements being recognized concerning the social, legal and institutional context from which workers' health laws emerged. Tension was noted concerning statutes orientated towards redress and compensation regarding accidents at work and legislation emphasizing prevention. PMID- 25123995 TI - [A case study regarding the technical and public health feasibility of collecting water from fog]. AB - OBJECTIVES: Evaluating the collection of water for human consumption from fog nets in San Antonio (Cundinamarca department). METHOD: Water was collected from fog using a prototype 6 m2sensor unit which was installed In the area for 53 days; this water was analysed to assess its quality regarding human consumption. RESULTS: The collection area's average daily volume was 43.26 L/day and the parameters evaluated met the minimum values established by local regulations for drinking water (RAS 2000), except for pH. CONCLUSION: This technique represents an alternative for obtaining water fit for human consumption and can be scaled-up to produce the quantity needed for communities living in low rainfall areas. It can thereby lead to improving such populations' health conditions. Its economic feasibility should thus be assessed regarding its implementation and sustainability. PMID- 25123996 TI - [Factors associated with exclusive breastfeeding until the sixth month in teenage mothers. Medellin, 2010]. AB - OBJECTIVE: Ascertaining factors associated with exclusive breastfeeding until the sixth month in teenage mothers included in SISBEN system levels I and II in the city of Medellin. METHODOLOGY: This was a case-control study which included 323 teenage mothers, involving 197 cases and 126 controls for the "Buen comienzo habia una vez -BCHV" (good start) strategy. Univariate analysis involved using descriptive statistics; a correspondence analysis was also made. Qualitative variables were compared using contingency tables and the Mann-Whitney U test was used for quantitative variables having non-normal distribution. Logistic regressions was used to identify factors associated with exclusive breastfeeding until the sixth month. Kapplan-Meier curves were made for the duration of breastfeeding and for the significant variable in the model. The attributable risk to which the population was exposed was calculated, as were population attributable risks. RESULTS: 27.9% of teenage mothers in the sample managed exclusive breastfeeding until the sixth month. Average maternal age was 17.56 years. Logistic regression analysis revealed that the time spent involved in the strategy and education following the birth of a child for those belonging to a nuclear family were associated with a longer duration of breastfeeding. CONCLUSIONS: The duration of exclusive breastfeeding in the teenage mother population could be extended, emphasizing continuity and the type of education received by being in the program. PMID- 25123997 TI - [Validating abbreviated developmental scale (ADS-1) criterion in the language hearing domain]. AB - OBJECTIVE: Establishing the validity of abbreviated developmental scale (ADS 1)criterion, regarding the language and hearing domain for 4- to 5-year-old children in the city of Popayan(2012). METHODS: This work involved a validation study of diagnostic tests for 96 children whose language and hearing were assessed by ADS-1 within a growth and development program and through speech therapy assessment as gold standard (Reynell norm-referenced test for measuring expressive and receptive language skills and tone audiometry and otoacoustic emissions for assessing hearing). The validity of the scale?s criterion was determined as was the correlation between both tests using the Kappa value. SPSS 19 was used for analyzing the results. RESULTS: The ADS-1 scale had 54 % sensitivity, 42 % specificity, 87 %positive predictive value, 11 % negative predictive value and K=-0.0 concordance. CONCLUSIONS: The ADS-1 scale has little predictive ability for correctly classifying a patient as being really ill and/or the healthy as being really sound. This value did not coincide with the prevalence found (87.5%). Poor agreement between both methods did not allow it to be classified as a valid instrument for use as a screening test for the early detection of language and hearing disorders in children aged 4 to 5 years old. PMID- 25123998 TI - Health risk represented by inhaling polycyclic aromatic hydrocarbons (PAH) during daily commuting involving using a high traffic flow route in Bogota. AB - OBJECTIVE: Assessing the risk to health by inhaling particles and particle-bound PAH during daily commuting along a high traffic flow route/corridor in Bogota. METHODS: A van was equipped with a PAS2000 photo-electric sensor for real-time measurement of particle-bound PAH and a Dust Trakfor monitoring PM10 concentration; it drove along typical commuting routes in the city. Exposure to particles and particle-bound PAH was assessed by using an inhalation intake model. RESULTS: A similar trend was observed for both PM10 and PAH concentration, indicating that traffic was the same source for both contaminants. Extreme PM10 and PAH inhalation concentrations were recorded every time direct bus and microbus emissions were measured by the van. Inhalation model results indicated that exposure was significantly greater when using a venues having mixed traffic use (i.e. buses, microbuses, passenger vehicles, motorcycles) compared to using roads where the TransMilenio system (articulated buses) had been implemented. CONCLUSIONS: The results may support evaluating bus drivers, commuters and bike users' exposure to toxic compounds in the city. PMID- 25123999 TI - [Respiratory disease risk factors in the 5-14 year-old population in an area of Bogota, 2012-2013]. AB - OBJECTIVE: Establishing the prevalence of respiratory symptoms, asthma and rhinitis, possibly associated with air pollution, in 5- to 14-year-old children in Bosa (a conurbation of Bogota), between 2012 and 2013. METHODS: A sample was taken of 553 children living in the conurbation. RESULTS: The results indicated that when a child lives with people who smoke there was a 1.5 times risk of coughing at night (compared to living in a non-smoking home) such night-time coughing being different to that produced by respiratory infections such as colds, bronchitis and pneumonia. Children living in homes having fireplaces/open cooking areas located less than 100 m apart had 1.6 times greater probability of presenting symptoms. Children attending schools having greater PM10 exposure and living near buildings being constructed or having roads in a poor state of repair less than 100 meters from their homes were 2.5 times more likely to suffer respiratory disease. Children living in damp rooms were 4 times more likely to have wheezed during the past year. The risk of wheezing became increased by 80 % when a child lived within 100 meters of buildings being constructed or near unpaved roads and attended a school having greater exposure. CONCLUSION: Government intervention is critical for changing respiratory disease-associated extramural risk factors, such as improvements benefitting children which should be carried out in urban areas. PMID- 25124000 TI - [The lack of water and its implications regarding feeding practice in Turbo, Antioquia]. AB - OBJECTIVE: Describing water-related perceptions and practice and how slum dwellers lacking public service coverage in the town of Turbo in the Antioquia Department, Colombia, approach this. METHODS: This study involved qualitative research from an ethnographic approach. Data was collected by means of interviews with slum dwellers and observing water-related activities. The information was encoded; empirical categories were initially constructed, followed by analytical ones. RESULTS: The families had established daily dynamics for facing life without water, investing time, money and effort and, according to their perceptions and possibilities, defining practice and uses for the water which they had access to. The available water sources consisted of a piped water supply which had to be paid for or was collected from other neighborhoods (considered unsuitable for drinking), rain water (appreciated for its taste and alleged quality) and bought bottled water (considered suitable for drinking and cooking, but more expensive than the piped water). Less suitable water sources were resorted to at critical moments during shortage. Regarding such deficiency, feeding practice became modified by replacing preparations requiring more water and making adjustments, thereby limiting what could be considered as suitable feeding. CONCLUSIONS: The lack of water affected the target families' food security, quality of life and welfare. Water-related practice corresponded to living conditions, meaning that biological and social aspects must be reconciled and recognized. The importance of the right to water and taking those suffering such deficiency in to consideration when making public health policy was thus highlighted. PMID- 25124001 TI - [The congenital syphilis protocol used at the Instituto Materno Infantil-Hospital la Victoria, Bogota]. AB - OBJECTIVES: Examining a cohort of women having a reactive venereal disease research laboratory (VDRL) test on delivery (and their newborn) to describe adherence to the Colombian treatment regime to prevent congenital syphilis and identify adverse clinical outcomes. METHODOLOGY: A descriptive study of 73 pregnant women and their new born was carried out at the Instituto Materno Infantil-Hospital La Victoria during 2008. RESULTS: Syphilis was detected in 50 women during their pregnancy and 23 when giving birth; 34 % became re-infected. 29 % were drug addicts, 19 % indigent and 23% had a history of syphilis. 7 cases were considered successful regarding antenatal treatment. Congenital syphilis frequency at the institution was 1 case per 46 births; there were 8 fetal deaths (12 %) and 58 cases of congenital syphilis in the newborn (27 symptomatic and 31 asymptomatic). 7 newborn had neurosyphilis, 17 suffered growth restriction and 6 were premature. Attending antenatal care, detecting syphilis during pregnancy and providing some type of treatment were related to decreased mortality, fewer symptomatic newborn and fewer infants having IUGR. Pregnant female drug addicts did not attend or lacked prenatal care and had a greater number of symptomatic newborn, involving growth restriction and being premature. CONCLUSIONS: It is recommended that pregnant women be encouraged to attend prenatal care and that health personnel should become involved in detecting the disease, verifying treatment in couples (i.e. including the sexual partner)and training in the institution's maternal and neonatal care programs. PMID- 25124002 TI - [Pharmacosurveillance regarding Colombian patients being treated with stavudine]. AB - OBJECTIVES: Reducing the occurrence of negative stavudine use-associated outcomes by reporting such risk to doctors responsible for the care of HIV/AIDS patients in Colombia as stavudine has been associated with cumulative and irreversible toxicity. METHODS: All stavudine users were identified from Audifarma S.A. (drug suppliers) databases (covering about 4.5 million people). The risk was then reported to health service providers and the substitution of stavudine for zidovudine or tenofovir was recommended. RESULTS: It was found that 1,410 patients registered in the afore mentioned databases were receiving antiretroviral therapy during 2010, of whom 109 (7.5 %) were receiving stavudine; these patients were living in 20 cities and being attended by 19 institutions. Stavudine use became reduced by 94.6 % during the 28 months following the intervention. Zidovudine was the most commonly used replacement drug. DISCUSSION: Stavudine was successfully replaced following World Health Organization recommendations aimed at preventing the occurrence of lipodystrophy and the peripheral neuropathy associated with its use. PMID- 25124003 TI - [Argentinean general practitioners' practice and counseling regarding physical activity]. AB - OBJECTIVE: Investigating general practitioners' (GP) physical activity and to what extent their own physical activity affects counselling their patients in clinical practice. METHODOLOGY: This was a cross-sectional, exploratory study; sample size was 115 (82 women and 33 men). The survey involved using a self administered questionnaire at the GPs' annual congress in 2011, using a specially designed, on-line questionnaire. RESULTS: This questionnaire revealed that about 76% of the female GPs did give advice concerning physical activity to their patients while the respective prevalence in men was 33 %. Regarding advice concerning physical activity to patients having non-communicable diseases, 73 % of women GPs always seemed to recommend physical activity for them while the corresponding prevalence in men was 27 %. Around 97 % (n=62) of the female GPs and 93 % (n=25) of male GPs asked their patients about their physical activity pattern; however, this study revealed that only 35 % (n=23) of male and 46 % (n=12) of female GPS were actually familiar with the latest recommendations concerning physical activity. CONCLUSION: No relationship was found between GPs' physical activity level and their counselling in practice concerning physical activity or their current knowledge of the topic. The study showed that GPs stated that physical activity was important for their patients, although few of them engaged in types of physical activity during their leisure-time. There would thus seem to be an urgent need for training GPs in prescribing physical activity at primary healthcare level to increase their patients' involvement in some form of physical activity. PMID- 25124004 TI - [A glossary for health care promoting universities (an HPU glossary)]. AB - The health promotion in the university context emerges as an important initiative to facilitate the development of healthy lifestyle behaviors in this environment where students, faculty and university staff spend and share a significant part of their lives. The movement of Health Promoting Universities (HPU) has over 20 years of experience, but still lacks a common language that allows effective communication between those who are interested in its planning and implementation. The purpose of this paper is to develop the most relevant concepts in the context of the international movement of UPS. This document is organized into five anchor dimensions: [1]The university and health promotion, [2] The University and its social responsibility, [3] The University, inequality and inequity, [4] The University and evidence in health promotion, and [5] Strategies to develop a HPU. It is hoped that this glossary for HPU encourages the development of a common language between those who promote this initiative and come from different disciplines, and at the same time serve as a guide for practice. PMID- 25124005 TI - [Causes of diabetic patients' indifference towards treatment, diet and monitoring and possible factors associated with such disease]. AB - OBJECTIVES: Analyze the causes of detachment to diet and treatment of patients with diabetes and factors associated with disease such as family history of diabetes and hypertension, in patients from one municipality of San Luis Potosi, Mexico, and surrounding areas. METHODS: Descriptive study of variables such as age, sex, schooling level, occupation, family history of diabetes and hypertension, causes of detachment to diet and treatment; analytic for groups in terms of the risk of diabetes according to socio demographic and family history. RESULTS: Of the 156 patients included main causes of detachment or abandonment of the indicated treatment and/or were the oblivion and insistence on restricted food intake. Patients with a family history of hypertension in both parents had 5.8 times the risk of Diabetes Mellitus, compared to those without this history (p<0.01). Those patients with a maternal history of diabetes had 4.76 times the risk of suffering it too, compared to those with only paternal history (p<0.001). For patients with a history of obesity, they had 2.4 times higher risk of developing diabetes than those who had not (p<0.05). CONCLUSIONS: Main causes, reported by patients, for detachment to treatment and diet were the oblivion and the insistence on restricted food intake, and the degree of association of Diabetes Mellitus with family history of this disease and hypertension is 2.4 to 5.8 times, with p<0.05. PMID- 25124007 TI - The heart of the matter: prime time E/e' prime! PMID- 25124006 TI - Determination of glutamate dehydrogenase activity and its kinetics in mouse tissues using metabolic mapping (quantitative enzyme histochemistry). AB - Glutamate dehydrogenase (GDH) catalyses the reversible conversion of glutamate into alpha-ketoglutarate with the concomitant reduction of NAD(P)(+) to NAD(P)H or vice versa. GDH activity is subject to complex allosteric regulation including substrate inhibition. To determine GDH kinetics in situ, we assessed the effects of various glutamate concentrations in combination with either the coenzyme NAD(+) or NADP(+) on GDH activity in mouse liver cryostat sections using metabolic mapping. NAD(+)-dependent GDH V(max) was 2.5-fold higher than NADP(+) dependent V(max), whereas the K(m) was similar, 1.92 mM versus 1.66 mM, when NAD(+) or NADP(+) was used, respectively. With either coenzyme, V(max) was determined at 10 mM glutamate and substrate inhibition was observed at higher glutamate concentrations with a K(i) of 12.2 and 3.95 for NAD(+) and NADP(+) used as coenzyme, respectively. NAD(+)- and NADP(+)-dependent GDH activities were examined in various mouse tissues. GDH activity was highest in liver and much lower in other tissues. In all tissues, the highest activity was found when NAD(+) was used as a coenzyme. In conclusion, GDH activity in mice is highest in the liver with NAD(+) as a coenzyme and highest GDH activity was determined at a glutamate concentration of 10 mM. PMID- 25124008 TI - Coronary involvement in lupus patients: getting sharper pictures with advanced vascular imaging? PMID- 25124009 TI - Contrast-enhanced CMR imaging of ventricular tachycardia isthmus sites to guide ablation: an approach in evolution. PMID- 25124010 TI - Does neointimal characterization following DES implantation predict long-term outcomes? PMID- 25124011 TI - Robot-assisted remote echocardiographic examination and teleconsultation: a randomized comparison of time to diagnosis with standard of care referral approach. AB - The strategy using cardiological consultation in addition to the robot-assisted remote echocardiography at a distance was tested in a prospective, randomized open-label trial to evaluate its feasibility and to define its clinical value in a rural area. The present study involved 1 primary healthcare center in the north of Sweden, 135 miles from the hospital where the echocardiograms and the cardiology teleconsultation were performed long distance in real time. Nineteen patients were randomized to remote consultation and imaging, and 19 to the standard of care consultation. The total process time was significantly reduced in the former arm (median 114 days vs. 26.5 days; p < 0.001). The time from randomization until attaining a specialist consultation was also significantly reduced (p < 0.001). The patients' satisfaction was reassuring; they considered that the remote consultation strategy offered an increased rapidity of diagnosis and the likelihood of receiving faster management compared with the standard of care at the primary healthcare center. PMID- 25124012 TI - Feasibility of intercity and trans-Atlantic telerobotic remote ultrasound: assessment facilitated by a nondedicated bandwidth connection. AB - We discuss the concept of ultrasound imaging at a distance by presenting the evaluation of a customized, lightweight, human-safe robotic arm for low-force, long-distance, telerobotic ultrasonography. We undertook intercity and trans Atlantic telerobotic ultrasound simulation from master stations located in New York, New York and Munich, Germany, and imaged a phantom and a human volunteer located at a slave station in Burlington, Massachusetts, using standard Internet bandwidth <100 Mbps and <50 Mbps, respectively. The data from the robotic arm were tracked for understanding the time efficiency of the human interactions at the master stations. Comparison of a beginner in ultrasound operation with a professional sonographer revealed that although proficiency in using ultrasound was not a prerequisite for operating the robotic arm, previous experience in using clinical ultrasound was associated with progressively lower probe maneuvering time and speed due to an enhanced ability of the veteran operator in adjusting the finer angular motions of the probe. These results suggest that long distance telerobotic echocardiography over a local nondedicated Internet bandwidth is feasible and can be rapidly learned by sonographers for cost effective resource utilization. PMID- 25124013 TI - Remote ultrasound: new opportunities. PMID- 25124014 TI - Ultrafast cardiac ultrasound imaging: technical principles, applications, and clinical benefits. AB - Several recent technical advances in cardiac ultrasound allow data to be acquired at a very high frame rate. Retrospective gating, plane/diverging wave imaging, and multiline transmit imaging all improve the temporal resolution of the conventional ultrasound system. The main drawback of such high frame rate data acquisition is that it typically has reduced image quality. However, for given clinical applications, the acquisition of temporally-resolved data might outweigh the reduction in image quality. It is the aim of this paper to provide an overview of the technical principles behind these new ultrasound imaging modalities, to review the current evidence of their potential clinical added value, and to forecast how they might influence daily clinical practice. PMID- 25124016 TI - FDG PET/CT imaging for LVAD associated infections. PMID- 25124017 TI - OCT imaging for the management of pulmonary hypertension. PMID- 25124018 TI - Delayed disruption of a bioresorbable vascular scaffold. PMID- 25124015 TI - Noninvasive imaging of cardiovascular injury related to the treatment of cancer. AB - The introduction of multiple treatments for cancer, including chemotherapeutic agents and radiation therapy, has significantly reduced cancer-related morbidity and mortality. However, these therapies can promote a variety of toxicities, among the most severe being the ones involving the cardiovascular system. Currently, for many surviving cancer patients, cardiovascular (CV) events represent the primary cause of morbidity and mortality. Recent data suggest that CV injury occurs early during cancer treatment, creating a substrate for subsequent cardiovascular events. Researchers have investigated the utility of noninvasive imaging strategies to detect the presence of CV injury during and after completion of cancer treatment because it starts early during cancer therapy, often preceding the development of chemotherapy or cancer therapeutics related cardiac dysfunction. In this State-of-the-Art Paper, we review the utility of current clinical and investigative CV noninvasive modalities for the identification and characterization of cancer treatment-related CV toxicity. PMID- 25124019 TI - Integrated 3D Echo-X-Ray navigation to predict optimal angiographic deployment projections for TAVR. PMID- 25124021 TI - Reply: Effects of blood T1 on extracellular volume calculation. PMID- 25124020 TI - Effects of blood T1 on extracellular volume calculation. PMID- 25124022 TI - Why, when, and how often?: The next steps after defining the right tools for noninvasive imaging of cardiotoxicity. PMID- 25124023 TI - Adapting to a changing health care environment. PMID- 25124024 TI - Stochastic population forecasting based on combinations of expert evaluations within the Bayesian paradigm. AB - This article suggests a procedure to derive stochastic population forecasts adopting an expert-based approach. As in previous work by Billari et al. (2012), experts are required to provide evaluations, in the form of conditional and unconditional scenarios, on summary indicators of the demographic components determining the population evolution: that is, fertility, mortality, and migration. Here, two main purposes are pursued. First, the demographic components are allowed to have some kind of dependence. Second, as a result of the existence of a body of shared information, possible correlations among experts are taken into account. In both cases, the dependence structure is not imposed by the researcher but rather is indirectly derived through the scenarios elicited from the experts. To address these issues, the method is based on a mixture model, within the so-called Supra-Bayesian approach, according to which expert evaluations are treated as data. The derived posterior distribution for the demographic indicators of interest is used as forecasting distribution, and a Markov chain Monte Carlo algorithm is designed to approximate this posterior. This article provides the questionnaire designed by the authors to collect expert opinions. Finally, an application to the forecast of the Italian population from 2010 to 2065 is proposed. PMID- 25124025 TI - Is tissue oxygen saturation related with complete blood parameters in ED patients? PMID- 25124026 TI - Cardiology clinic follow-up did not decrease return visits to the ED for chest pain patients. AB - BACKGROUND: We initiated a program to rapidly rule out myocardial infarction and make an appointment (with no co-payment) with a cardiologist within 72 hours for patients with low-risk chest pain. OBJECTIVE: The objectives of this study were to determine if the rate of return emergency department (ED) visits for chest pain decreased among patients who kept their appointments and to evaluate factors that impacted clinic no-show rates. METHODS: The study was conducted at a safety net facility with 65 000 adult patient visits per year. This study was a retrospective review of patients with chest pain discharged from the ED with a scheduled cardiology clinic appointment between October 2008 and December 2009. We compared those who kept their clinic appointment with those who did not for repeat ED visits for 6 months after the study period. Multivariate analysis evaluated factors associated with keeping appointments. RESULTS: Of 381 patients, 265 (70%) kept their appointments. Show rates did not differ based on age, sex, race, or language. Patients with commercial insurance were more likely to keep appointments than Medicare, Medicaid, and uninsured (OR, 51.3; 95% confidence interval [CI], 2.53-1041.64; P = .010). The 116 no-show patients averaged 0.39 return ED visits (95% CI, 0.15-0.63), and the 265 patients who kept their appointments averaged 0.28 (95% CI, 0.17-0.39). Two hundred twenty-nine patients who kept their appointment had no return ED visits, but 36 patients had 74 return ED visits. There was no difference in return ED visits between the 18 who had diagnostic cardiac testing (mean, 1.78; 95% CI, 1.60-3.06) and the 18 who did not (mean, 2.33; 95% CI, 1.20-2.36; P = .251). CONCLUSIONS: This program did not reduce repeat ED visits. Patients with insurance were more likely to keep follow up appointments. PMID- 25124027 TI - Computed tomography scan as a diagnostic tool for supraglottitis in adults. PMID- 25124029 TI - Effects of familiar contingencies on infants' vocal behavior in new communicative contexts. AB - Recently, there has been a growing interest in understanding the mechanisms underlying vocal learning in songbirds and human infants. Research has demonstrated how contingent social feedback from social partners to immature vocalizations can play a role during vocal learning in both brown-headed cowbirds and prelinguistic infants. Contingencies in social interactions, particularly familiar contingencies, are important in developing preferences for social partners and shaping social exchanges Bigelow and Birch [1999]. Infant Behavior & Development 22:367-382]; however, little is known about how familiar contingencies that individuals experience during communicative exchanges play a role in new contexts. The current study examined differences in caregiver response patterns to infant vocal behavior and assessed how familiar contingencies influenced infant vocal behavior in novel communicative exchanges with caregivers. Infants were systematically exposed to high and low social feedback schedules during a play session. Results revealed the frequency of caregiver responsiveness to which infants were accustomed to affected infant vocal production during novel communicative situations. Infants with high responding caregivers vocalized with more mature vocalizations and used their vocalizations differently than infants with low responding caregivers during the high, but not low, response period. Specifically, infants with high responding caregivers directed more of their vocalizations at their caregiver and looked more at their caregiver after vocalizing, an indication of anticipating contingent responding. These results suggest that infants with high responding caregivers learned the association between vocalizing and contingent responses during the novel communicative interaction. This study demonstrates the need to understand how infants who experience a variety of contingencies in everyday interactions with caregivers carry over to other interactive situations. PMID- 25124028 TI - Patient factors associated with identification of sepsis in the ED. PMID- 25124030 TI - The effect of spine postures on the hydrodynamic drag in Epinephelus ongus larvae. AB - Laboratory behavioural observation and computational fluid dynamics (CFD) analysis were conducted to examine whether the movement of the elongated dorsal and pelvic spines changed the hydrodynamic drag in white-streaked grouper Epinephelus ongus larvae. The behavioural observation in the tank revealed that the larvae extended the dorsal and pelvic spines during passive transport and retracted during swimming; the angles of the dorsal and pelvic spines in relation to the anteroposterior axis were larger during the passive transport (mean +/- S.D. = 28.84 +/- 14.27 and 20.35 +/- 15.05 degrees ) than those during the swimming (mean +/- S.D. = 2.59 +/- 5.55 and 0.32 +/- 6.49 degrees ). The CFD analysis indicated that the relative hydrodynamic drag acting on the larvae was approximately 1.25 times higher when the spines were extended (passive transport) than when the spines were retracted (swimming), suggesting that the E. ongus larvae have an ability to adjust their hydrodynamic drag depending on the behavioural context. PMID- 25124031 TI - Astrocytic inclusions in progressive supranuclear palsy and corticobasal degeneration. AB - Tufted astrocytes (TAs) in progressive supranuclear palsy (PSP) and astrocytic plaques (APs) in corticobasal degeneration (CBD) have been regarded as the pathological hallmarks of major sporadic 4-repeat tauopathies. To better define the astrocytic inclusions in PSP and CBD and to outline the pathological features of each disease, we reviewed 95 PSP cases and 30 CBD cases that were confirmed at autopsy. TAs exhibit a radial arrangement of thin, long, branching accumulated tau protein from the cytoplasm to the proximal processes of astrocytes. APs show a corona-like arrangement of tau aggregates in the distal portions of astrocytic processes and are composed of fuzzy, short processes. Immunoelectron microscopic examination using quantum dot nanocrystals revealed filamentous tau accumulation of APs located in the immediate vicinity of the synaptic structures, which suggested synaptic dysfunction by APs. The pathological subtypes of PSP and CBD have been proposed to ensure that the clinical phenotypes are in accordance with the pathological distribution and degenerative changes. The pathological features of PSP are divided into 3 representative subtypes: typical PSP type, pallido nigro-luysian type (PNL type), and CBD-like type. CBD is divided into three pathological subtypes: typical CBD type, basal ganglia- predominant type, and PSP like type. TAs are found exclusively in PSP, while APs are exclusive to CBD, regardless of the pathological subtypes, although some morphological variations exist, especially with regard to TAs. The overlap of the pathological distribution of PSP and CBD makes their clinical diagnosis complicated, although the presence of TAs and APs differentiate these two diseases. The characteristics of tau accumulation in both neurons and glia suggest a different underlying mechanism with regard to the sites of tau aggregation and fibril formation between PSP and CBD: proximal-dominant aggregation of TAs and formation of filamentous NFTs in PSP in contrast to the distal-dominant aggregation of APs and formation of less filamentous pretangles in CBD. PMID- 25124032 TI - Ca2+-mediated mitochondrial reactive oxygen species metabolism augments Wnt/beta catenin pathway activation to facilitate cell differentiation. AB - Emerging evidence suggests that reactive oxygen species (ROS) can stimulate the Wnt/beta-catenin pathway in a number of cellular processes. However, potential sources of endogenous ROS have not been thoroughly explored. Here, we show that growth factor depletion in human neural progenitor cells induces ROS production in mitochondria. Elevated ROS levels augment activation of Wnt/beta-catenin signaling that regulates neural differentiation. We find that growth factor depletion stimulates the release of Ca(2+) from the endoplasmic reticulum stores. Ca(2+) subsequently accumulates in the mitochondria and triggers ROS production. The inhibition of mitochondrial Ca(2+) uptake with simultaneous growth factor depletion prevents the rise in ROS metabolism. Moreover, low ROS levels block the dissociation of the Wnt effector Dishevelled from nucleoredoxin. Attenuation of the response amplitudes of pathway effectors delays the onset of the Wnt/beta catenin pathway activation and results in markedly impaired neuronal differentiation. Our findings reveal Ca(2+)-mediated ROS metabolic cues that fine tune the efficiency of cell differentiation by modulating the extent of the Wnt/beta-catenin signaling output. PMID- 25124033 TI - Degradation of Tiam1 by casein kinase 1 and the SCFbetaTrCP ubiquitin ligase controls the duration of mTOR-S6K signaling. AB - Tiam1 (T-cell lymphoma invasion and metastasis 1) is a guanine nucleotide exchange factor that specifically controls the activity of the small GTPase Rac, a key regulator of cell adhesion, proliferation, and survival. Here, we report that in response to mitogens, Tiam1 is degraded by the ubiquitin-proteasome system via the SCF(betaTrCP) ubiquitin ligase. Mitogenic stimulation triggers the binding of Tiam1 to the F-box protein betaTrCP via its degron sequence and subsequent Tiam1 ubiquitylation and proteasomal degradation. The proteolysis of Tiam1 is prevented by betaTrCP silencing, inhibition of CK1 and MEK, or mutation of the Tiam1 degron site. Expression of a stable Tiam1 mutant that is unable to interact with betaTrCP results in sustained activation of the mTOR/S6K signaling and increased apoptotic cell death. We propose that the SCF(betaTrCP)-mediated degradation of Tiam1 controls the duration of the mTOR-S6K signaling pathway in response to mitogenic stimuli. PMID- 25124034 TI - Interfacial partitioning of a loop hinge residue contributes to diacylglycerol affinity of conserved region 1 domains. AB - Conventional and novel isoenzymes of PKC are activated by the membrane-embedded second messenger diacylglycerol (DAG) through its interactions with the C1 regulatory domain. The affinity of C1 domains to DAG varies considerably among PKCs. To gain insight into the origin of differential DAG affinities, we conducted high-resolution NMR studies of C1B domain from PKCdelta (C1Bdelta) and its W252Y variant. The W252Y mutation was previously shown to render C1Bdelta less responsive to DAG (Dries, D. R., Gallegos, L. L., and Newton, A. C. (2007) A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production. J. Biol. Chem. 282, 826-830) and thereby emulate the behavior of C1B domains from conventional PKCs that have a conserved Tyr at the equivalent position. Our data revealed that W252Y mutation did not perturb the conformation of C1Bdelta in solution but significantly reduced its propensity to partition into a membrane-mimicking environment in the absence of DAG. Using detergent micelles doped with a paramagnetic lipid, we determined that both the residue identity at position 252 and complexation with diacylglycerol influence the geometry of C1Bdelta-micelle interactions. In addition, we identified the C-terminal helix alpha1 of C1Bdelta as an interaction site with the head groups of phosphatidylserine, a known activator of PKCdelta. Taken together, our studies (i) reveal the identities of C1Bdelta residues involved in interactions with membrane-mimicking environment, DAG, and phosphatidylserine, as well as the affinities associated with each event and (ii) suggest that the initial ligand-independent membrane recruitment of C1B domains, which is greatly facilitated by the interfacial partitioning of Trp-252, is responsible, at least in part, for the differential DAG affinities. PMID- 25124035 TI - Systematic analysis of bacterial effector-postsynaptic density 95/disc large/zonula occludens-1 (PDZ) domain interactions demonstrates Shigella OspE protein promotes protein kinase C activation via PDLIM proteins. AB - Diseases caused by many Gram-negative bacterial pathogens depend on the activities of bacterial effector proteins that are delivered into eukaryotic cells via specialized secretion systems. Effector protein function largely depends on specific subcellular targeting and specific interactions with cellular ligands. PDZ domains are common domains that serve to provide specificity in protein-protein interactions in eukaryotic systems. We show that putative PDZ binding motifs are significantly enriched among effector proteins delivered into mammalian cells by certain bacterial pathogens. We use PDZ domain microarrays to identify candidate interaction partners of the Shigella flexneri effector proteins OspE1 and OspE2, which contain putative PDZ-binding motifs. We demonstrate in vitro and in cells that OspE proteins interact with PDLIM7, a member of the PDLIM family of proteins, which contain a PDZ domain and one or more LIM domains, protein interaction domains that participate in a wide variety of functions, including activation of isoforms of protein kinase C (PKC). We demonstrate that activation of PKC during S. flexneri infection is attenuated in the absence of PDLIM7 or OspE proteins and that the OspE PDZ-binding motif is required for wild-type levels of PKC activation. These results are consistent with a model in which binding of OspE to PDLIM7 during infection regulates the activity of PKC isoforms that bind to the PDLIM7 LIM domain. PMID- 25124036 TI - Human trefoil factor 2 is a lectin that binds alpha-GlcNAc-capped mucin glycans with antibiotic activity against Helicobacter pylori. AB - Helicobacter pylori infection is the major cause of gastric cancer and remains an important health care challenge. The trefoil factor peptides are a family of small highly conserved proteins that are claimed to play essential roles in cytoprotection and epithelial repair within the gastrointestinal tract. H. pylori colocalizes with MUC5AC at the gastric surface epithelium, but not with MUC6 secreted in concert with TFF2 by deep gastric glands. Both components of the gastric gland secretome associate non-covalently and show increased expression upon H. pylori infection. Although blood group active O-glycans of the Lewis-type form the basis of H. pylori adhesion to the surface mucin layer and to epithelial cells, alpha1,4-GlcNAc-capped O-glycans on gastric mucins were proposed to inhibit H. pylori growth as a natural antibiotic. We show here that the gastric glycoform of TFF2 is a calcium-independent lectin, which binds with high specificity to O-linked alpha1,4-GlcNAc-capped hexasaccharides on human and porcine stomach mucin. The structural assignments of two hexasaccharide isomers and the binding active glycotope were based on mass spectrometry, linkage analysis, (1)H nuclear magnetic resonance spectroscopy, glycan inhibition, and lectin competition of TFF2-mucin binding. Neoglycolipids derived from the C3/C6 linked branches of the two isomers revealed highly specific TFF2 binding to the 6 linked trisaccharide in GlcNAcalpha1-4Galbeta1-4GlcNAcbeta1-6(Fucalpha1-2Galbeta1 3)GalNAc-ol(Structure 1). Supposedly, lectin TFF2 is involved in protection of gastric epithelia via a functional relationship to defense against H. pylori launched by antibiotic alpha1,4-GlcNAc-capped mucin glycans. Lectin-carbohydrate interaction may have also an impact on more general functional aspects of TFF members by mediating their binding to cell signaling receptors. PMID- 25124037 TI - Control of Toll-like receptor-mediated T cell-independent type 1 antibody responses by the inducible nuclear protein IkappaB-zeta. AB - Antibody responses have been classified as being either T cell-dependent or T cell-independent (TI). TI antibody responses are further classified as being either type 1 (TI-1) or type 2 (TI-2), depending on their requirement for B cell mediated antigen receptor signaling. Although the mechanistic basis of antibody responses has been studied extensively, it remains unclear whether different antibody responses share similarities in their transcriptional regulation. Here, we show that mice deficient in IkappaB-zeta, specifically in their B cells, have impaired TI-1 antibody responses but normal T cell-dependent and TI-2 antibody responses. The absence of IkappaB-zeta in B cells also impaired proliferation triggered by Toll-like receptor (TLR) activation, plasma cell differentiation, and class switch recombination (CSR). Mechanistically, IkappaB-zeta-deficient B cells could not induce TLR-mediated induction of activation-induced cytidine deaminase (AID), a class-switch DNA recombinase. Retroviral transduction of AID in IkappaB-zeta-deficient B cells restored CSR activity. Furthermore, acetylation of histone H3 in the vicinity of the transcription start site of the gene that encodes AID was reduced in IkappaB-zeta-deficient B cells relative to IkappaB zeta-expressing B cells. These results indicate that IkappaB-zeta regulates TLR mediated CSR by inducing AID. Moreover, IkappaB-zeta defines differences in the transcriptional regulation of different antibody responses. PMID- 25124038 TI - Biochemical characterization of mutants in chaperonin proteins CCT4 and CCT5 associated with hereditary sensory neuropathy. AB - Hereditary sensory neuropathies are a class of disorders marked by degeneration of the nerve fibers in the sensory periphery neurons. Recently, two mutations were identified in the subunits of the eukaryotic cytosolic chaperonin TRiC, a protein machine responsible for folding actin and tubulin in the cell. C450Y CCT4 was identified in a stock of Sprague-Dawley rats, whereas H147R CCT5 was found in a human Moroccan family. As with many genetically identified mutations associated with neuropathies, the underlying molecular basis of the mutants was not defined. We investigated the biochemical properties of these mutants using an expression system in Escherichia coli that produces homo-oligomeric rings of CCT4 and CCT5. Full-length versions of both mutant protein chains were expressed in E. coli at levels approaching that of the WT chains. Sucrose gradient centrifugation revealed chaperonin-sized complexes of both WT and mutant chaperonins, but with reduced recovery of C450Y CCT4 soluble subunits. Electron microscopy of negatively stained samples of C450Y CCT4 revealed few ring-shaped species, whereas WT CCT4, H147R CCT5, and WT CCT5 revealed similar ring structures. CCT5 complexes were assayed for their ability to suppress aggregation of and refold the model substrate gammad-crystallin, suppress aggregation of mutant huntingtin, and refold the physiological substrate beta-actin in vitro. H147R CCT5 was not as efficient in chaperoning these substrates as WT CCT5. The subtle effects of these mutations are consistent with the homozygous disease phenotype, in which most functions are carried out during development and adulthood, but some selective function is lost or reduced. PMID- 25124039 TI - The mitochondrial ADP/ATP carrier associates with the inner membrane presequence translocase in a stoichiometric manner. AB - The majority of mitochondrial proteins are synthesized with amino-terminal signal sequences. The presequence translocase of the inner membrane (TIM23 complex) mediates the import of these preproteins. The essential TIM23 core complex closely cooperates with partner protein complexes like the presequence translocase-associated import motor and the respiratory chain. The inner mitochondrial membrane also contains a large number of metabolite carriers, but their association with preprotein translocases has been controversial. We performed a comprehensive analysis of the TIM23 interactome based on stable isotope labeling with amino acids in cell culture. Subsequent biochemical studies on identified partner proteins showed that the mitochondrial ADP/ATP carrier associates with the membrane-embedded core of the TIM23 complex in a stoichiometric manner, revealing an unexpected connection of mitochondrial protein biogenesis to metabolite transport. Our data indicate that direct TIM23 AAC coupling may support preprotein import into mitochondria when respiratory activity is low. PMID- 25124040 TI - Biosynthesis and translocation of unsulfated acyltrehaloses in Mycobacterium tuberculosis. AB - A number of species-specific polymethyl-branched fatty acid-containing trehalose esters populate the outer membrane of Mycobacterium tuberculosis. Among them, 2,3 diacyltrehaloses (DAT) and penta-acyltrehaloses (PAT) not only play a structural role in the cell envelope but also contribute to the ability of M. tuberculosis to multiply and persist in the infected host, promoting the intracellular survival of the bacterium and modulating host immune responses. The nature of the machinery, topology, and sequential order of the reactions leading to the biosynthesis, assembly, and export of these complex glycolipids to the cell surface are the object of the present study. Our genetic and biochemical evidence corroborates a model wherein the biosynthesis and translocation of DAT and PAT to the periplasmic space are coupled and topologically split across the plasma membrane. The formation of DAT occurs on the cytosolic face of the plasma membrane through the action of PapA3, FadD21, and Pks3/4; that of PAT occurs on the periplasmic face via transesterification reactions between DAT substrates catalyzed by the acyltransferase Chp2 (Rv1184c). The integral membrane transporter MmpL10 is essential for DAT to reach the cell surface, and its presence in the membrane is required for Chp2 to be active. Disruption of mmpL10 or chp2 leads to an important build-up of DAT inside the cells and to the formation of a novel form of unsulfated acyltrehalose esterified with polymethyl branched fatty acids normally found in sulfolipids that is translocated to the cell surface. PMID- 25124041 TI - Allosteric regulation of a protein acetyltransferase in Micromonospora aurantiaca by the amino acids cysteine and arginine. AB - ACT domains (amino acid-binding domains) are linked to a wide range of metabolic enzymes that are regulated by amino acid concentration. Seventy proteins with ACT GCN5-related N-acetyltransferase (GNAT) domain organization were found in actinomycetales. In this study, we investigate the ACT-containing GNAT acetyltransferase, Micau_1670 (MaKat), from Micromonospora aurantiaca ATCC 27029. Arginine and cysteine were identified as ligands by monitoring the conformational changes that occur upon amino acids binding to the ACT domain in the MaKat protein using FRET assay. It was found that MaKat is an amino acid-regulated protein acetyltransferase, whereas arginine and cysteine stimulated the activity of MaKat with regard to acetylation of acetyl-CoA synthetase (Micau_0428). Our research reveals the biochemical characterization of a protein acetyltransferase that contains a fusion of a GNAT domain with an ACT domain and provides a novel signaling pathway for regulating cellular protein acetylation. These findings indicate that acetylation of proteins and acetyltransferase activity may be tightly linked to cellular concentrations of some amino acids in actinomycetales. PMID- 25124042 TI - Crystal structure of the ubiquitin-like domain-CUT repeat-like tandem of special AT-rich sequence binding protein 1 (SATB1) reveals a coordinating DNA-binding mechanism. AB - SATB1 is essential for T-cell development and growth and metastasis of multitype tumors and acts as a global chromatin organizer and gene expression regulator. The DNA binding ability of SATB1 plays vital roles in its various biological functions. We report the crystal structure of the N-terminal module of SATB1. Interestingly, this module contains a ubiquitin-like domain (ULD) and a CUT repeat-like (CUTL) domain (ULD-CUTL tandem). Detailed biochemical experiments indicate that the N terminus of SATB1 (residues 1-248, SATB1((1-248))), including the extreme 70 N-terminal amino acids, and the ULD-CUTL tandem bind specifically to DNA targets. Our results show that the DNA binding ability of full-length SATB1 requires the contribution of the CUTL domain, as well as the CUT1-CUT2 tandem domain and the homeodomain. These findings may reveal a multiple-domain coordinated mechanism whereby SATB1 recognizes DNA targets. PMID- 25124044 TI - Newborn screening for pompe disease? a qualitative study exploring professional views. AB - BACKGROUND: Developments in enzyme replacement therapy have kindled discussions on adding Pompe disease, characterized by progressive muscle weakness and wasting, to neonatal screening. Pompe disease does not fit traditional screening criteria as it is a broad-spectrum phenotype disorder that may occur in lethal form in early infancy or manifest in less severe forms from infancy to late adulthood. Current screening tests cannot differentiate between these forms. Normally, expanding screening is discussed among experts in advisory bodies. While advisory reports usually mention the procedures and outcome of deliberations, little is known of the importance attached to different arguments and the actual weighing processes involved. In this research we aim to explore the views of a wide range of relevant professionals to gain more insight into the process of weighing pros and cons of neonatal screening for Pompe disease, as an example of the dilemmas involved in screening for broad-spectrum phenotype disorders. METHODS: We conducted 24 semi-structured interviews with medical, lab, insurance and screening professionals, and executive staff of patient organisations. They were asked about their first reaction to neonatal screening for Pompe disease, after which benefits and harms and requirements for screening were explored in more detail. RESULTS: Advantages included health gain by timely intervention, avoiding a diagnostic quest, having a reproductive choice and gaining more knowledge about the natural course and treatment. Being prepared was mentioned as an advantage for the later manifesting cases. Disadvantages included treatment costs and uncertainties about its effect, the timing of treatment in later manifesting cases, the psychological burden for the patient-in-waiting and the family. Also the downsides of having prior knowledge as well as having to consider a reproductive option were mentioned as disadvantages. CONCLUSION: When weighing pros and cons, interviewees attach different importance to different arguments, based on personal and professional views. Professionals expect benefits from neonatal screening for Pompe disease, especially for early-onset cases. Some interviewees valued screening in later manifesting cases as well, while stressing the need for adequate support of pre-symptomatic patients and their families. Others considered the psychological burden and uncertainties regarding treatment as reasons not to screen. PMID- 25124043 TI - Shutdown of achaete-scute homolog-1 expression by heterogeneous nuclear ribonucleoprotein (hnRNP)-A2/B1 in hypoxia. AB - The basic helix-loop-helix transcription factor hASH1, encoded by the ASCL1 gene, plays an important role in neurogenesis and tumor development. Recent findings indicate that local oxygen tension is a critical determinant for the progression of neuroblastomas. Here we investigated the molecular mechanisms underlying the oxygen-dependent expression of hASH1 in neuroblastoma cells. Exposure of human neuroblastoma-derived Kelly cells to 1% O2 significantly decreased ASCL1 mRNA and hASH1 protein levels. Using reporter gene assays, we show that the response of hASH1 to hypoxia is mediated mainly by post-transcriptional inhibition via the ASCL1 mRNA 5'- and 3'-UTRs, whereas additional inhibition of the ASCL1 promoter was observed under prolonged hypoxia. By RNA pulldown experiments followed by MALDI/TOF-MS analysis, we identified heterogeneous nuclear ribonucleoprotein (hnRNP)-A2/B1 and hnRNP-R as interactors binding directly to the ASCL1 mRNA 5'- and 3'-UTRs and influencing its expression. We further demonstrate that hnRNP A2/B1 is a key positive regulator of ASCL1, findings that were also confirmed by analysis of a large compilation of gene expression data. Our data suggest that a prominent down-regulation of hnRNP-A2/B1 during hypoxia is associated with the post-transcriptional suppression of hASH1 synthesis. This novel post transcriptional mechanism for regulating hASH1 levels will have important implications in neural cell fate development and disease. PMID- 25124045 TI - Prospective study of ultrasound-guided percutaneous renal cryotherapy: case selection as an optimization factor for a technique. AB - OBJECTIVE: To evaluate the technical and oncological effectiveness of ultrasound guided percutaneous renal cryotherapy (PRC) in a selected group of patients with renal cancer. MATERIAL AND METHODS: We conducted a prospective study of 28 patients with posterior-facing T1a renal tumors with middle and inferior external borders. All patients underwent ultrasound-guided PRC. Follow-up was conducted with computed tomography at 1 month and then every 6 months, with a good result defined as the total absence of contrast incorporation. We performed a descriptive and survival study using the Kaplan-Meier estimator. RESULTS: The 28 patients had a mean age (SD) of 68.3 (10.1) years, and the group underwent 28 procedures. The mean (SD) size of the tumors was 25.5 (7.5) mm, the mean nephrometry score was 1.41 (0.52) and the mean preoperative creatinine level was 133.5 (144.1) mmol/L. There were no intraoperative complications. In terms of postoperative complications, there was only 1 case (3.5%) of a skin lesion resulting from treating a tumor in a transplanted kidney (Clavien II). The median follow-up was 25 months, and the mean (SD) postoperative creatinine level was 135.5 (110.3) mmol/L. Two cases presented radiological recurrence (93% efficacy), with a mean time to recurrence of 12 and 19 months, respectively. There were no tumor-related deaths. CONCLUSIONS: Our series (the largest on PRC in our country to date) shows that, with an appropriate selection of tumors, PRC is a safe technique with minimal morbidity. Ultrasonography enables the controlled performance of the procedure and saves the patient from radiation and reduces costs. PMID- 25124046 TI - Opisthorchis viverrini: analysis of the sperm-specific rhophilin associated tail protein 1-like. AB - Concurrent deficiency of rhophilin associated tail protein (ROPN1) and ROPN1-like (ROPN1L) in mice causes structural abnormalities and immotility of sperm and thereby infertility. In the present research, ROPN1L of the human liver fluke Opisthorchis viverrini was molecularly characterized and showed unexpected potential as a diagnostic tool. ROPN1L transcripts were detected in 2-week-old juveniles by RT-PCR. Immunohistochemical analysis of the adult worm localized the protein in testis lobes, seminal vesicle and receptacle and immunoelectron microscopic analysis revealed its location on the tail of spermatozoa. Interestingly, sera of experimentally infected hamsters and sera of individuals suffering from opisthorchiasis showed reactivity to recombinant OvROPN1L (rOvROPN1L). The protein shows modest conservation to the human homolog at 47.2% sequence identity and a mouse anti-rOvROPN1L antiserum was not reactive with sperm protein extracts from hamsters, mice and rats. Unsurprisingly, conservation is higher in trematodes, e.g. 78.4% and 71.2% identity to Fasciola gigantica and Schistosoma haematobium, respectively and evaluation of diagnostic specificity is required using sera of individuals suffering from different trematodiases in Thailand. PMID- 25124048 TI - A-site sub-stoichiometry and oxygen vacancies as the origin of the electrical properties of Sr2-yLuNb1-xTixO6-delta perovskite-like materials. AB - Aliovalent substitution of Nb(5+) by Ti(4+) in Sr2LuNbO6 is limited to 10% of Nb atoms. A full structural determination by NPD confirms this and reveals that the structure is better described as a superstructure of the simple cubic perovskite (as previously reported) with the monoclinic cell 2(1/2)ap* 2(1/2)ap* 2ap and beta~ 90 degrees (S.G. P21/n). The substituted materials present both oxygen vacancies induced by charge compensation and Sr-deficiency. Therefore, their formula should be given as Sr2-yLuNb1-xTixO6-delta. Electrical properties can be fully understood considering these compositional defects. The parent compound Sr2LuNbO6 presents low electrical conductivity in air, which improves by more than one order of magnitude upon Ti substitution. In any case, the title oxides show low electrical conductivity in a wide oxygen partial pressure (pO2) range (10(-25) atm <=pO2<= 10(-1) atm). At high pO2 the conductivity increases with pO2 due to oxygen-vacancy annihilation and hole creation, according to a general p type semiconducting mechanism; A-site substoichiometry and Ti-substitution are the origin of this behaviour. In the low pO2 region, the conductivity increases as the oxygen partial pressure decreases. Reduction of cations, Nb(5+) or Ti(4+), supports n-type conduction by electrons and oxygen vacancy creation. For the intermediate pO2 range a low ionic conduction contribution is observed. Although the estimated ionic conductivity is not high in the substituted compounds, the strategy seems to be valid since a significant enhancement of ionic conduction is observed upon aliovalent substitution. PMID- 25124047 TI - A meta-analysis of external fixator versus intramedullary nails for open tibial fracture fixation. AB - BACKGROUND: To compare the clinical outcomes of external fixator (EF) and intramedullary nails (IN) in the treatment of open tibial fractures. METHODS: We searched seven electronic databases (PubMed, MEDLINE, EMBASE, OVID, Cochrane library, CNKI, and CBM) for trials of tibial fracture fixation published from 1980 to 2013. The indicators including postoperative infection, malunion, nonunion, soft tissue injury, delayed healing, and healing time were used for quantitative outcome assessments. RESULTS: A total of nine trials involving 532 patients (EF, n = 253; IN, n = 279) with open tibia fractures were included in this meta-analysis. The results indicated that the patients undergoing IN had lower incidence of postoperative infection (risk radio [RR] = 3.85; 95% confidence intervals [CI], 2.67-5.54; P < 0.0001), malunion (RR = 2.31; 95% CI, 1.40-3.81; P = 0.001), nonunion (RR = 1.41; 95% CI, 1.06-1.88; P = 0.02) and less healing time (weighted mean difference [WMD] = 6.19; 95% CI, 1.42-10.96; P = 0.01) compared with EF. However, regarding to the soft tissue injury (RR = 0.74; 95% CI, 0.34-1.62; P = 0.45) and delayed healing (RR = 1.38; 95% CI, 0.79-2.43; P = 0.26), there is no significantly difference between EF and IN approach. CONCLUSION: In conclusion, the use of IN is more effective than EF and may be considered as first-line approach in fixation of open tibial fractures. PMID- 25124049 TI - The solid-state continuum: a perspective on the interrelationships between different solid-state forms in drug substance and drug product. AB - OBJECTIVE: The objective of the review is to provide an overview of the nomenclature used in the solid-state continuum and relate these to the development of drug substances and drug products. KEY FINDINGS: The importance of a rational approach to solid-state form selection, including integrated decision making (ensuring equal weight is given to the needs of the drug substance and the drug product), is vital for the effective development of a drug candidate. For example, how do secondary processing considerations influence the selection of drug substance solid-state form and resulting formulation, and how can drug substance solid-state form be used to optimise secondary processing? Further, the potential use of 'crystal' engineering to optimise stability, purity and optical resolutions, and the linked regulatory requirements, will be discussed. SUMMARY: The nomenclature used in the solid-state continuum, which contains a large number of different crystalline and non-crystalline forms, for example, amorphous systems, was reviewed. Further, the significant role of the drug substance within the solid oral dose form from a physicochemical perspective was covered. PMID- 25124050 TI - Childhood trauma and eating psychopathology: a mediating role for dissociation and emotion dysregulation? AB - The present study examined the relationship between different forms of childhood trauma and eating psychopathology using a multiple mediation model that included emotion dysregulation and dissociation as hypothesised mediators. 142 female undergraduate psychology students studying at two British Universities participated in this cross-sectional study. Participants completed measures of childhood trauma (emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect), eating psychopathology, dissociation and emotion dysregulation. Multiple mediation analysis was conducted to investigate the study's proposed model. Results revealed that the multiple mediation model significantly predicted eating psychopathology. Additionally, both emotion dysregulation and dissociation were found to be significant mediators between childhood trauma and eating psychopathology. A specific indirect effect was observed between childhood emotional abuse and eating psychopathology through emotion dysregulation. Findings support previous research linking childhood trauma to eating psychopathology. They indicate that multiple forms of childhood trauma should be assessed for individuals with eating disorders. The possible maintaining role of emotion regulation processes should also be considered in the treatment of eating disorders. PMID- 25124051 TI - Exploring policies for the reduction of child physical abuse and neglect. AB - Policies can be powerful tools for prevention given their potential to affect conditions that can improve population-level health. Given the dearth of empirical research on policies' impacts on child maltreatment, this article (a) identifies 37 state policies that might have impacts on the social determinants of child maltreatment; (b) identifies available data sources documenting the implementation of 31 policies; and (c) utilizes the available data to explore effects of 11 policies (selected because they had little missing data) on child maltreatment rates. These include two policies aimed at reducing poverty, two temporary assistance to needy families policies, two policies aimed at increasing access to child care, three policies aimed at increasing access to high quality pre-K, and three policies aimed at increasing access to health care. Multi-level regression analyses between within-state trends of child maltreatment investigation rates and these 11 policies, controlling for states' childhood poverty, adults without a high school diploma, unemployment, child burden, and race/ethnicity, identified two that were significantly associated with decreased child maltreatment rates: lack of waitlists to access subsidized child care and policies that facilitate continuity of child health care. These findings are correlational and are limited by the quality and availability of the data. Future research might focus on a reduced number of states that have good quality administrative data or population-based survey data on child maltreatment or reasonable proxies for child maltreatment and where data on the actual implementation of specific policies of interest can be documented. PMID- 25124052 TI - Computed tomographic findings in 15 dogs with eosinophilic bronchopneumopathy. AB - Eosinophilic bronchopneumopathy is a disease characterized by the infiltration of the lung and bronchial mucosa by eosinophils. The aim of the present study was to describe the CT findings in a large series of dogs with confirmed diagnosis of eosinophilic bronchopneumopathy. Computed tomographic scans of 15 dogs with confirmed diagnosis of eosinophilic bronchopneumopathy were evaluated retrospectively by two boarded radiologists who reached a consensus. Abnormalities were identified in 14/15 (93%) dogs, including pulmonary parenchymal abnormalities in 14/15 (93%) dogs, bronchial wall thickening in 13 (87%) dogs, which was considered marked in eight (53%), plugging of the bronchial lumen by mucus/debris in 11 (73%) dogs, and bronchiectasis in nine (60%) dogs. Pulmonary nodules were identified in 5/15 (33%) dogs including one dog with a mass. All dogs with a nodular lung pattern had additional abnormalities. Lymphadenopathy was present in 10 dogs (67%). Lesions associated with eosinophilic bronchopneumopathy are variable and heterogeneous and encompass a wider variety of computed tomographic features than reported previously. Computed tomographic images were abnormal in the majority of affected dogs, hence CT is a useful modality to characterize the nature and distribution of thoracic lesions in dogs with eosinophilic bronchopneumopathy. PMID- 25124053 TI - VMAT2 and Parkinson's disease: old dog, new tricks. PMID- 25124055 TI - Cytostatic drugs and metabolites in municipal and hospital wastewaters in Spain: filtration, occurrence, and environmental risk. AB - Concerns about cytostatic anticancer drugs in the environment are increasing, mainly due to the lack of knowledge about the fate and impact of these cytotoxic compounds in the water cycle. In this context, the present work investigated the occurrence of 13 cytostatics and 4 metabolites in wastewater samples from various wastewater treatment plants (WWTPs) and from a large hospital from Spain. The target compounds belong to five different classes according to the Anatomical Therapeutic Classification (ATC), namely, alkylating agents, antimetabolites, plant alkaloids and other natural products, cytotoxic antibiotics and related substances, and other antineoplastic agents. Some of them have been classified as carcinogens in humans by the International Agency for Research on Cancer (IARC). These compounds were determined by an automated on line solid-phase extraction liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method. Results showed the presence of methotrexate (MET), ifosfamide (IF), cyclophosphamide (CP), irinotecan (IRI), doxorubicin (DOX), capecitabine (CAP), tamoxifen (TAM) and the metabolites endoxifen (OH-D-TAM), hydroxytamoxifen (OH-TAM) and hydroxypaclitaxel (OH-PAC) at levels ranging from 2 ng L(-1) (for MET) to 180 ng L(-1) (for TAM). Some of these compounds were found to be efficiently removed after wastewater treatment, e.g. MET, DOX and IRI, whereas other compounds, such as TAM, CP and IF remained largely unaltered. The behaviour of the target compounds during the common filtration step of the water samples was also investigated with the finding that some compounds are strongly adsorbed to nylon filters, while cellulose acetate appears as the best choice for the filter material. The aquatic environmental risk associated to the detected compounds was also assessed. To the best of the authors' knowledge, this is the first report of the presence of the metabolites OH-D-TAM and OH-TAM in the water cycle. PMID- 25124054 TI - Correlation between optical coherence tomography-derived intraluminal parameters and fractional flow reserve measurements in intermediate grade coronary lesions: a comparison between diabetic and non-diabetic patients. AB - BACKGROUND: Fractional flow reserve (FFR) measurements accurately assess functional relevance in intermediate grade coronary lesions. A significant relationship between hemodynamic stenosis severity and optical coherence tomography (OCT)-derived intraluminal dimensions has recently been demonstrated. However, morphologic thresholds to identify significant stenoses are variable and exploration of this correlation in patients with diabetes mellitus (DM) remains currently incomplete. This study aimed at comparing the diagnostic value of intraluminal parameters as determined by OCT to predict FFR <=0.8 in lesions of patients with versus without DM. METHODS: In 100 patients (DM = 56, non-DM = 44) with 142 coronary de novo lesions (DM = 80, non-DM = 62) of intermediate grade as determined by quantitative coronary angiography, we performed OCT and FFR. Stenoses were defined functionally relevant if FFR was <=0.8. RESULTS: FFR measurements in the overall study cohort, the DM and the non-DM group correlated significantly with minimal lumen area (MLA) [overall: r (2) = 0.339, DM: r (2) = 0.341, non-DM: r (2) = 0.355 (all p < 0.001)], percent area stenosis [overall: r (2) = 0.352, DM: r (2) = 0.376, non-DM: r (2) = 0.351 (all p < 0.001)] and minimal lumen diameter [overall: r (2) = 0.333, DM: r (2) = 0.277, non-DM: r (2) = 0.417 (all p < 0.001)] without differing statistically between diabetic and non diabetic patients (p = ns). Receiver operating characteristic analysis demonstrated that among OCT-derived parameters, MLA predicted FFR <=0.8 with the best diagnostic efficiency and with similar cut-off values for all patients [area under the curve (AUC) = 0.836, 95% confidence interval (CI) = 0.772-0.901, cut off value = 1.64 mm(2)] as well as for diabetic (AUC = 0.840, 95% CI = 0.754 0.927, cut-off value = 1.59 mm(2)) and non-diabetic subjects (AUC = 0.833, 95% CI = 0.734-0.932, cut-off value = 1.64 mm(2)). CONCLUSION: In both, diabetic and non diabetic patients, FFR and OCT-derived intraluminal measurements are significantly correlated and OCT predicts hemodynamically relevant coronary stenosis with moderate diagnostic efficiency. PMID- 25124056 TI - Effects of nano-ZnO on the agronomically relevant Rhizobium-legume symbiosis. AB - The impact of nano-ZnO (nZnO) on Rhizobium-legume symbiosis was studied with garden pea and its compatible bacterial partner Rhizobium leguminosarum bv. viciae 3841. Exposure of peas to nZnO had no impact on germination, but significantly affected root length. Chronic exposure of plant to nZnO impacted its development by decreasing the number of the first- and the second-order lateral roots, stem length, leaf surface area, and transpiration. The effect of nZnO dissolution on phytotoxicity was also examined. Results showed that Zn(2+) had negative impact on plant development. Exposure of R. leguminosarum bv. viciae 3841 to nZnO brought about morphological changes by rendering the microbial cells toward round shape and damaging the bacterial surface. Furthermore, the presence of nZnO in the rhizosphere affected root nodulation, delayed the onset of nitrogen fixation, and caused early senescence of nodules. Attachment of nanoparticles on the root surface and dissolution of Zn(2+) are important factors affecting the phytotocity of nZnO. Hence, the presence of nZnO in the environment is potentially hazardous to the Rhizobium-legume symbiosis system. PMID- 25124057 TI - Foster care, externalizing disorders, and antipsychotic use among Medicaid enrolled youths. AB - OBJECTIVES: The authors investigated the extent to which clinical diagnoses of externalizing disorders explain higher rates of antipsychotic use by foster care youths. METHODS: Medicaid claims data from 44 states for 2009 for youths in foster care (N=301,894) and those not in foster care (N=5,092,574) were analyzed, excluding those with schizophrenia, bipolar disorder, autism, and major depressive disorder. Logistic regressions assessed the relationship between foster care, externalizing disorders, and antipsychotic use. RESULTS: Foster care youths had higher rates of externalizing disorders than the comparison group (attention-deficit hyperactivity disorder, 17.3% versus 6.5%; disruptive behavior disorder, 7.2% versus 2.5%; conduct disorder, 2.3% versus .5%) and greater antipsychotic use (7.4% versus 1.4%). Foster care remained a significant predictor of antipsychotic use after control for demographic and diagnostic covariates, including externalizing disorders (adjusted odds ratio=2.59, 95% confidence interval=2.54-2.63). CONCLUSIONS: High rates of externalizing disorder diagnoses only partially explained elevated levels of antipsychotic use in this vulnerable population. PMID- 25124058 TI - Granulation of increasingly hydrophobic formulations using a twin screw granulator. AB - The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has not yet been established. Hence, the current work investigated the granulation behaviour of three formulations containing increasing amounts of hydrophobic components using a ConsigmaTM-1 twin screw granulator. Process conditions including powder feed rate, liquid to solid ratio, granulation liquid composition and screw configuration were also evaluated. The size of the wet granules was measured in order to enable exploration of granulation behaviour in isolation without confounding effects from downstream processes such as drying. The experimental observations indicated that the granulation process was not sensitive to the powder feed rate. The hydrophobicity led to heterogeneous liquid distribution and hence a relatively large proportion of un-wetted particles. Increasing numbers of kneading elements led to high shear and prolonged residence time, which acted to enhance the distribution of liquid and feeding materials. The bimodal size distributions considered to be characteristic of twin screw granulation were primarily ascribed to the breakage of relatively large granules by the kneading elements. PMID- 25124059 TI - Amphiphilic chitosan-grafted-functionalized polylactic acid based nanoparticles as a delivery system for doxorubicin and temozolomide co-therapy. AB - The aim of this work was to investigate the potential of an amphiphilic system comprising chitosan-grafted polylactide and carboxyl-functionalized polylactide acid as a carrier for the controlled release and co-release of two DNA alkylating drugs: doxorubicin and temozolomide. Polylactide and carboxyl-functionalized polylactide acid were obtained through direct melt polycondensation reaction, using methanesulfonic acid as a non-toxic initiator, and subsequently these were grafted to the chitosan backbone through a coupling reaction, utilizing 1-ethyl-3 (3-dimethylaminopropyl) carbodiimide as a condensing agent. ATR-FTIR analysis and conductometric titration confirmed that a reaction between CS and PLA, PLACA2% and PLACA5% occurred. Chitosan-grafted-polylactide and polylactide-citric acid nanoparticles were prepared via the polyelectrolyte complex technique, applying dextran sulphate as a polyanion, and loaded with doxorubicin and temozolomide. The diameter of particles, zeta-potential and their relationship to temperature and pH were analysed in all formulations. Encapsulation, co-encapsulation efficiency and release studies were conducted in different physiological simulated environments and human serum. Results showed the continuous release of drugs without an initial burst in different physiological media. PMID- 25124060 TI - Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. AB - Positron emission tomography-CT (PET-CT) is one of the initial mediastinal staging modality for non-small cell lung cancer; however, the clinical utility in carcinoid tumours is uncertain. We sought to determine the test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. We collated data from seven institutions, performing a retrospective search on pathological databases for a consecutive series of patients who underwent thoracic surgery (with lymph nodal dissection) for carcinoid tumours with preoperative PET-CT staging. PET-CT results were compared with the reference standard of pathologic results obtained from lymph node dissection and test performance reported using sensitivity and specificity. From November 1999 to January 2013, 247 patients from seven institutions underwent surgery for carcinoid tumours with a corresponding preoperative PET-CT scan. The mean age of the patients was 61 (SD 15, range 73) and 84 were male patients (34%). The pathologic subtype was typical carcinoid in 217 patients (88%) and atypical carcinoid in 30 patients (12%). Results from lymph node dissection were obtained in 207 patients. The calculated sensitivity and specificity of PET-CT to identify mediastinal lymph node disease was 33% (95% CI 4% to 78%) and 94% (95% CI 89% to 97%), respectively. Our results indicate that PET-CT has a poor sensitivity but good specificity to detect the presence of mediastinal lymph node metastases in pulmonary carcinoid tumours. Mediastinal lymph node metastases cannot be ruled out with negative PET-CT uptake, and if the absence of mediastinal lymph node disease is a prerequisite for directing management, tissue sampling should be undertaken. PMID- 25124063 TI - An unusual stacking transformation in liquid-crystalline columnar assemblies of clicked molecular propellers with tunable light emissions. AB - The columnar liquid-crystalline (LC) and fluorescence properties of three dimensional molecular propellers based on tetraphenylethylene is reported. X-ray scattering studies reveal an unusual transition from a rectangular (Colrec ) to a hexagonal columnar (Colhex ) phase. In contrast to second-order intercolumnar transitions based on a common tilt mechanism, the transition is first order and involves an unprecedented zigzag stacking of aromatic propellers in the Colrec phase. A sudden change in emission color from sky blue to green occurs rapidly and reversibly at this transition, which is due to the planarization of the propeller mesogen. PMID- 25124061 TI - Prevention of infections during primary immunodeficiency. AB - Because infectious diseases are a major source of morbidity and mortality in the majority of patients with primary immunodeficiencies (PIDs), the application of a prophylactic regimen is often necessary. However, because of the variety of PIDs and pathogens involved, and because evidence is scarce, practices are heterogeneous. To homogenize practices among centers, the French National Reference Center for PIDs aimed at elaborating recommendations for anti infectious prophylaxis for the most common PIDs. We performed a literature review of infectious complications and prophylactic regimens associated with the most frequent PIDs. Then, a working group including different specialists systematically debated about chemoprophylaxis, immunotherapy, immunization, and recommendations for patients. Grading of prophylaxis was done using strength of recommendations (decreasing from A to D) and evidence level (decreasing from I to III). These might help infectious diseases specialists in the management of PIDs and improving the outcome of patients with PIDs. PMID- 25124064 TI - The impact of genetic heterogeneity on biomarker development in kidney cancer assessed by multiregional sampling. AB - Primary clear cell renal cell carcinoma (ccRCC) genetic heterogeneity may lead to an underestimation of the mutational burden detected from a single site evaluation. We sought to characterize the extent of clonal branching involving key tumor suppressor mutations in primary ccRCC and determine if genetic heterogeneity could limit the mutation profiling from a single region assessment. Ex vivo core needle biopsies were obtained from three to five different regions of resected renal tumors at a single institution from 2012 to 2013. DNA was extracted and targeted sequencing was performed on five genes associated with ccRCC (von-Hippel Lindau [VHL], PBRM1, SETD2, BAP1, and KDM5C). We constructed phylogenetic trees by inferring clonal evolution based on the mutations present within each core and estimated the predictive power of detecting a mutation for each successive tumor region sampled. We obtained 47 ex vivo biopsy cores from 14 primary ccRCC's (median tumor size 4.5 cm, IQR 4.0-5.9 cm). Branching patterns of various complexities were observed in tumors with three or more mutations. A VHL mutation was detected in nine tumors (64%), each time being present ubiquitously throughout the tumor. Other genes had various degrees of regional mutational variation. Based on the mutations' prevalence we estimated that three different tumor regions should be sampled to detect mutations in PBRM1, SETD2, BAP1, and/or KDM5C with 90% certainty. The mutational burden of renal tumors varies by region sampled. Single site assessment of key tumor suppressor mutations in primary ccRCC may not adequately capture the genetic predictors of tumor behavior. PMID- 25124066 TI - Targeted genome regulation and modification using transcription activator-like effectors. AB - Transcription activator-like effectors (TALEs) are immensely powerful new tools for genome engineering that can be directed to bind to almost any DNA sequence of choice. They originate from the Xanthomonas species of plant pathogenic bacteria and, in nature, these proteins increase the virulence of Xanthomonas. However, in 2009, the DNA binding code of TALEs was deciphered and, subsequently, TALE proteins have been exploited for many diverse applications. Custom TALEs that target almost any required DNA sequence can be readily constructed in < 1 week. One major application is gene editing: TALEs fused with the Fok I endonuclease catalytic domain can induce double-stranded breaks at a chosen genomic location, similar to zinc finger nucleases. Designer TALE transcription factors have also been developed by linking TALEs to a transcription AD, such as VP64. More recently, TALEs have been developed that can repress transcription, bind methylated DNA or act as fluorescent chromatin probes. In the present review, we describe the assembly of designer TALEs, their expanding range of current and potential future applications, and briefly discuss alternatives, namely, zinc finger nucleases and clustered regularly interspaced short palindromic repeat/clustered regularly interspaced short palindromic repeat associated protein 9. PMID- 25124065 TI - Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity. AB - BACKGROUND: Classic galactosemia (OMIM #230400) is an autosomal recessive metabolic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) protein due to mutations in the GALT gene. The aim of this study was to provide a comprehensive and updated mutation spectrum of GALT in a Korean population. METHODS: Thirteen unrelated patients screened positive for galactosemia in a newborn screening program were included in this study. They showed a reduced GALT enzyme activity in red blood cells. Direct sequencing of the GALT gene and in silico analyses were done to evaluate the impact of novel variations upon GALT enzyme activity. We also reviewed previous reports for GALT mutations in Koreans. RESULTS: We identified six novel likely pathogenic variations including three missense (p.Ala101Asp, p.Tyr165His, and p.Pro257Thr), one small deletion/insertion [c.826_827delinsAA (p.Ala276Asn)], one frameshift (p.Asn96Serfs*5), and one splicing (c.378-1G > C) likely pathogenic variations. The most frequent variation was the Duarte variant (c.940A > G, 35.3%), followed by c.507G > C (p.Gln169His, 9.6%), among 34 Korean patients. Other mutations were widely scattered. None of the eight common mutations used for targeted mutation analysis in Western countries including p.Gln188Arg, p.Ser135Leu, p.Lys285Asn, p.Leu195Pro, p.Tyr209Cys, p.Phe171Ser, c.253-2A > G, and a 5 kb deletion, had been found in Koreans until this study. CONCLUSIONS: Considering the mutation spectrum in Koreans, direct sequence analysis of entire GALT exons is recommended for accurate diagnosis. The mutations responsible for GALT deficiency in the Korean population were clearly different from those of other populations. PMID- 25124067 TI - Living cardiac tissue slices: an organotypic pseudo two-dimensional model for cardiac biophysics research. AB - Living cardiac tissue slices, a pseudo two-dimensional (2D) preparation, have received less attention than isolated single cells, cell cultures, or Langendorff perfused hearts in cardiac biophysics research. This is, in part, due to difficulties associated with sectioning cardiac tissue to obtain live slices. With moderate complexity, native cell-types, and well-preserved cell-cell electrical and mechanical interconnections, cardiac tissue slices have several advantages for studying cardiac electrophysiology. The trans-membrane potential (Vm) has, thus far, mainly been explored using multi-electrode arrays. Here, we combine tissue slices with optical mapping to monitor Vm and intracellular Ca(2+) concentration ([Ca(2+)]i). This combination opens up the possibility of studying the effects of experimental interventions upon action potential (AP) and calcium transient (CaT) dynamics in 2D, and with relatively high spatio-temporal resolution. As an intervention, we conducted proof-of-principle application of stretch. Mechanical stimulation of cardiac preparations is well-established for membrane patches, single cells and whole heart preparations. For cardiac tissue slices, it is possible to apply stretch perpendicular or parallel to the dominant orientation of cells, while keeping the preparation in a constant focal plane for fluorescent imaging of in-slice functional dynamics. Slice-to-slice comparison furthermore allows one to assess transmural differences in ventricular tissue responses to mechanical challenges. We developed and tested application of axial stretch to cardiac tissue slices, using a manually-controlled stretching device, and recorded Vm and [Ca(2+)]i by optical mapping before, during, and after application of stretch. Living cardiac tissue slices, exposed to axial stretch, show an initial shortening in both AP and CaT duration upon stretch application, followed in most cases by a gradual prolongation of AP and CaT duration during stretch maintained for up to 50 min. After release of sustained stretch, AP duration (APD) and CaT duration reverted to shorter values. Living cardiac tissue slices are a promising experimental model for the study of cardiac mechano electric interactions. The methodology described here can be refined to achieve more accurate control over stretch amplitude and timing (e.g. using a computer controlled motorised stage, or by synchronising electrical and mechanical events) and through monitoring of regional tissue deformation (e.g. by adding motion tracking). PMID- 25124068 TI - Mathematical modeling for evolution of heterogeneous modules in the brain. AB - Modular architecture has been found in most cortical areas of mammalian brains, but little is known about its evolutionary origin. It has been proposed by several researchers that maximizing information transmission among subsystems can be used as a principle for understanding the development of complex brain networks. In this paper, we study how heterogeneous modules develop in coupled map networks via a genetic algorithm, where selection is based on maximizing bidirectional information transmission. Two functionally differentiated modules evolved from two homogeneous systems with random couplings, which are associated with symmetry breaking of intrasystem and intersystem couplings. By exploring the parameter space of the network around the optimal parameter values, it was found that the optimum network exists near transition points, at which the incoherent state loses its stability and an extremely slow oscillatory motion emerges. PMID- 25124069 TI - Memories as bifurcations: realization by collective dynamics of spiking neurons under stochastic inputs. AB - How the neural system proceeds from sensory stimuli to generate appropriate behaviors is a basic question that has not yet been fully answered. In contrast to the conventional viewpoint, in which the external stimulus dominantly drives the response behavior, recent studies have revealed that not only external stimuli, but also intrinsic neural dynamics, contribute to the generation of response behavior. In particular, spontaneous activity, which is neural activity without extensive external stimuli, has been found to exhibit similar patterns to those evoked by external inputs, from time to time. In order to further understand the role of this spontaneous activity on the response, we propose a viewpoint, memories-as-bifurcations, that differs from the traditional memories as-attractors viewpoint. According to this viewpoint, memory is recalled when spontaneous neural activity is changed to an appropriate output activity upon the application of an input. After reviewing the previous rate-coding model embodying this viewpoint, we employ a model of a spiking neuron network that can embed input/output associations, and study the dynamics of collective neural activity. The organized neural activity, which matched the target pattern, is shown to be generated even under application of stochastic input, while the spontaneous activity, which apparently shows noisy dynamics, is found to exhibit selectively higher similarity with evoked activities corresponding to embedded target patterns. These results suggest that such an intrinsic structure in the spontaneous activity might play a role in generating the higher response. The relevance of these results to biological neural processing is also discussed. PMID- 25124070 TI - Bronchoscopic interventions for chronic obstructive pulmonary disease. AB - Over the past decade, several non-surgical and minimally invasive bronchoscopic lung volume reduction (BLVR) techniques have been developed to treat patients with severe chronic obstructive pulmonary disease (COPD). BLVR can be significantly efficacious, suitable for a broad cohort of patients, and associated with a solid safety profile at a reasonable expense. The introduction of BLVR is also expected to accelerate the further development of interventional pulmonology worldwide. Recently, results from clinical studies on BLVR techniques have been published, providing valuable information about the procedure's indications, contraindications, patient-selection criterion and outcomes. BLVR utilizing one-way endobronchial valves is gaining momentum as an accepted treatment in regular medical practice because of the identification of best responders. Patients with a heterogeneous emphysema distribution and without inter-lobar collateral ventilation show encouraging results. Furthermore, for patients with collateral ventilation, who are not considered candidates for valve treatment, and for patients with homogeneous emphysema, the introduction of lung volume reduction coil treatment is a promising solution. Moreover, with the development of newer treatment modalities, that is, biochemical sealant and thermal water vapor, the potential to treat emphysema irrespective of collateral flow, may be further increased. Nevertheless, patient selection for BLVR treatment will be crucial for the procedure's success and should be performed using a multidisciplinary team approach. Consequently, BLVR needs to be concentrated in high-volume centres that will offer better quality and experience with treatment challenges and adverse events. This review gives a general overview of BLVR from an expert and scientific perspective. PMID- 25124071 TI - Bullet points from SHOT: key messages and recommendations from the Annual SHOT Report 2013. PMID- 25124072 TI - Seroepidemiology of human T-cell lymphotropic virus among Iranian adult thalassemic patients. AB - BACKGROUND: A large number of transfusion-dependent thalassemic patients is at a substantial risk for transfusion-transmitted infections. Human T-cell lymphotropic virus (HTLV) is a blood-borne pathogen and can be transmitted via cellular products. We aimed to evaluate the seroprevalence of HTLV in transfusion dependent thalassemic patients referred to Tehran Adult Thalassemia Clinic. METHODS: From 2008 to 2010, 257 transfusion-dependent thalassemic patients who referred to Tehran Adult Thalassemia Clinic were enrolled. The seroprevalence of HTLV, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV were assessed using enzyme-linked immunosorbant assay (ELISA). Also, the samples with positive result for anti-HTLVAb (by ELISA) were reassessed using Western blot for HTLV. RESULTS: Among the 257 transfusion-dependent thalassemic patients who were tested for anti-HTLVAb, 29 (11.3%, 95% CI = 7.8-15.6%) were found to be anti-HTLVAb positive by ELISA and Western blot. No case was detected to be HBsAg positive, whereas 16% had HBV seroconversion criteria, and more than 95% had anti-HBsAb in their sera. Also, 103 (40.1%) patients were HCV seropositive, 13 (5.1%) patients of which were co-infected with HCV/HTLV. Among the HTLV-infected patients, 44.8% were co-infected with HCV, whereas 39.5% of HTLV-seronegative individuals were HCV mono-infected (P > 0.05). CONCLUSION: This study showed that transfusion dependent thalassemic patients were in higher risk for transmission of different blood-borne pathogens such as HTLV. The screening of HTLV in Iranian blood donors is recommended. PMID- 25124073 TI - Pulsed-high-dose dexamethasone as a treatment for pure red cell aplasia following ABO-incompatible allogeneic stem cell transplantation. PMID- 25124074 TI - Two cases of platelet transfusion refractoriness and one case of possible FNAIT caused by antibodies against CD36 in China. PMID- 25124075 TI - Chaperone network composition in Solanum lycopersicum explored by transcriptome profiling and microarray meta-analysis. AB - Heat shock proteins (Hsps) are molecular chaperones primarily involved in maintenance of protein homeostasis. Their function has been best characterized in heat stress (HS) response during which Hsps are transcriptionally controlled by HS transcription factors (Hsfs). The role of Hsfs and Hsps in HS response in tomato was initially examined by transcriptome analysis using the massive analysis of cDNA ends (MACE) method. Approximately 9.6% of all genes expressed in leaves are enhanced in response to HS, including a subset of Hsfs and Hsps. The underlying Hsp-Hsf networks with potential functions in stress responses or developmental processes were further explored by meta-analysis of existing microarray datasets. We identified clusters with differential transcript profiles with respect to abiotic stresses, plant organs and developmental stages. The composition of two clusters points towards two major chaperone networks. One cluster consisted of constitutively expressed plastidial chaperones and other genes involved in chloroplast protein homeostasis. The second cluster represents genes strongly induced by heat, drought and salinity stress, including HsfA2 and many stress-inducible chaperones, but also potential targets of HsfA2 not related to protein homeostasis. This observation attributes a central regulatory role to HsfA2 in controlling different aspects of abiotic stress response and tolerance in tomato. PMID- 25124076 TI - Vascular endothelial growth factor A polymorphism and risk of Kaposi's sarcoma herpesvirus viremia in kidney allograft recipients. AB - BACKGROUND: Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease in immunocompromised patients including allograft recipients. Detection of KSHV DNA in blood, as well as host genetic polymorphisms has been found to be associated with an increased risk for KS. We investigated an association between single nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA) gene region and KSHV viremia in kidney transplant recipients (KTR) in Saudi Arabia. METHODS: In total, 152 KTR who have survived kidney transplantation for at least 6 months were included in the study. KSHV viremia was determined by real time polymerase chain reaction (PCR). Genotyping of SNPs in the VEGFA region was performed by PCR and direct sequencing, as well as by restriction fragment length polymorphism. RESULTS: KSHV DNA was detected in 28.9% (n = 44) of the study population. The A-allele at position C172A VEGFA gene promoter region was found to be associated with KSHV viremia (odd ratio [OR] = 4.8, P = 0.005). In addition, the G-allele at position C+405G in the 5'-untranslated region was associated with KSHV viremia in women, but not in men (OR = 3.98, P = 0.004). CONCLUSIONS: Our results suggest an association of VEGFA polymorphisms with KSHV viremia among KTR in this study population. A limitation of our study is that the results can only be predicated for patients 6 months after kidney transplantation and should be validated in another cohort with larger sample size. PMID- 25124077 TI - Study of the usability of spaced retrieval exercise using mobile devices for Alzheimer's disease rehabilitation. AB - BACKGROUND: Alzheimer's disease (AD) is an irreversible brain disease that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest daily tasks. Recent studies showed that people with AD might actually benefit from physical exercises and rehabilitation processes. Studies show that rehabilitation would also add value in making the day for an individual with AD a little less foggy, frustrating, isolated, and stressful for as long as possible. OBJECTIVE: The focus of our work was to explore the use of modern mobile technology to enable people with AD to improve their abilities to perform activities of daily living, and hence to promote independence and participation in social activities. Our work also aimed at reducing the burden on caregivers by increasing the AD patients' sense of competence and ability to handle behavior problems. METHODS: We developed ADcope, an integrated app that includes several modules that targeted individuals with AD, using mobile devices. We have developed two different user interfaces: text-based and graphic-based. To evaluate the usability of the app, 10 participants with early stages of AD were asked to run the two user interfaces of the spaced retrieval memory exercise using a tablet mobile device. RESULTS: We selected 10 participants with early stages of AD (average age: 75 years; 6/10, 60% males, 4/10, 40% females). The average elapsed time per question between the text-based task (14.04 seconds) and the graphic-based task (12.89 seconds) was significantly different (P=.047). There was also a significant difference (P<.001) between the average correct answer score between the text-based task (7.60/10) and the graphic-based task (8.30/10), and between the text-based task (31.50/100) and the graphic-based task (27.20/100; P<.001). Correlation analysis for the graphic-based task showed that the average elapsed time per question and the workload score were negatively correlated (-.93, and -.79, respectively) to the participants' performance (P<.001 and P=.006, respectively). CONCLUSIONS: We found that people with early stages of AD used mobile devices successfully without any prior experience in using such devices. Participants' measured workload scores were low and posttask satisfaction in fulfilling the required task was conceivable. Results indicate better performance, less workload, and better response time for the graphic-based task compared with the text-based task. PMID- 25124078 TI - Evaluation of treatment outcomes for patients on first-line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses. AB - OBJECTIVES: Viral load (VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief (PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here. METHODS: In this cross-sectional, observational study, patients on first-line antiretroviral therapy (ART) (efavirenz or nevirapine+zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load (HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6-12, 13-24 or >24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART. RESULTS: We found that 85.2% of 325 subjects were virologically suppressed (viral load<47 HIV-1 RNA copies/ml). There was no difference in the proportion of virologically suppressed subjects by time on treatment, yet CD4 counts were higher in each successive stratum. Women had higher median CD4 counts than men overall (406 vs. 294 cells/MUL, respectively; P<0.0001) and in each time-on treatment stratum. In a multivariate logistic regression model, predictors of virological suppression included efavirenz use [odds ratio (OR) 0.47; 95% confidence interval (CI) 0.22-1.02; P=0.057], lower cost of clinic visits (OR 0.815; 95% CI 0.66-1.00; P=0.05), improvement in CD4 percentage (OR 1.06; 95% CI 1.014-1.107; P=0.009), and care at Kayunga vs. Kangulamira (OR 0.47; 95% CI 0.23 0.92; P=0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy (ART) (P<0.0001), patient satisfaction with care (P=0.038), improvements in total lymphocyte count (P<0.0001) and haemoglobin concentration (P=0.05) were positively associated, whereas age at start of ART (P=0.0045) was negatively associated with this outcome. CONCLUSIONS: High virological suppression rates are achievable on first-line ART in Uganda. The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to the clinic. CD4 cell reconstitution was positively associated with CD4 count at study visit, time on ART, satisfaction with care at clinic, haemoglobin concentration and total lymphocyte count and negatively associated with age. PMID- 25124079 TI - Stigma and the perpetuation of obesity. AB - Even as obesity rates reach new highs, the social stigmatization of obesity seems to be strengthening and globalizing. This review identifies at least four mechanisms by which a pervasive environment of fat stigma could reinforce high body weights or promote weight gain, ultimately driving population-level obesity. These are direct effects through behavior change because of feeling judged, and indirect effects of social network changes based on stigmatizing actions and decisions by others, psychosocial stress from feeling stigmatized, and the structural effects of discrimination. Importantly, women and children appear especially vulnerable to these mechanisms. The broader model provides an improved basis to investigate the role of stigma in driving the etiology of obesity, and explicates how individual, interpersonal, and structural dimensions of stigma are connected to variation in health outcomes, including across generations. PMID- 25124080 TI - Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro. AB - Exercise has been shown to reduce risk and improve prognosis of several types of cancers. Irisin is a myokine linked to exercise and lean body mass, which is thought to favorably alter metabolism systemically, potentially providing benefit for metabolic disease (including cancer). We evaluated the effects of various concentrations of irisin (with and without post-translational modifications) on malignant and non-malignant breast epithelial cell number, migration and viability. Irisin significantly decreased cell number, migration and viability in malignant MDA-MB-231 cells, without affecting non-malignant MCF-10a cells. Moreover, irisin enhanced the cytotoxic effect of doxorubicin (Dox) when added to a wide spectrum of irisin concentrations in the malignant cell type (with simultaneous reduction in Dox uptake), which was not observed in non-malignant MCF-10a cells. Additionally, we found that irisin decreases malignant cell viability in part through stimulation of caspase activity leading to apoptotic death. Interestingly, we found that irisin suppresses NFkappaB activation, an opposite effect of other myokines such as tumor necrosis factor alpha (TNF alpha). Our observations suggest that irisin may offer therapeutic benefits for breast cancer prevention and treatment possibly through an anti-inflammatory response, induction of apoptotic cell death, or through enhanced tumor sensitivity to common antineoplastic agents such as Dox. PMID- 25124081 TI - Resmethrin, the first modern pyrethroid insecticide. AB - The discovery of resmethrin almost five decades ago was the seminal event in the development of pyrethroid insecticides as important pest management tools, the value of which endures to this day. This brief review considers the development of pyrethroids from the perspective of the discovery of resmethrin. I describe the pathway to the discovery of resmethrin and the unique properties that differentiated it from the pyrethrins and earlier synthetic pyrethroids is described. I also summarize information on metabolic fate and mechanisms of selective toxicity, first elucidated with resmethrin, that have shaped our understanding of pyrethroid toxicology since that time. Finally, I review the discovery pathway that led from resmethrin to the development of the first photostable, agriculturally useful pyrethroids that established the importance of this insecticide class. PMID- 25124082 TI - In vivo magnetic resonance imaging of tumor protease activity. AB - Increased expression of cathepsins has diagnostic as well as prognostic value in several types of cancer. Here, we demonstrate a novel magnetic resonance imaging (MRI) method, which uses poly-L-glutamate (PLG) as an MRI probe to map cathepsin expression in vivo, in a rat brain tumor model. This noninvasive, high-resolution and non-radioactive method exploits the differences in the CEST signals of PLG in the native form and cathepsin mediated cleaved form. The method was validated in phantoms with known physiological concentrations, in tumor cells and in an animal model of brain tumor along with immunohistochemical analysis. Potential applications in tumor diagnosis and evaluation of therapeutic response are outlined. PMID- 25124083 TI - Community-based family-style group homes for children orphaned by AIDS in rural China: an ethnographic investigation. AB - As the number of children orphaned by AIDS (Acquired Immunodeficiency Syndrome) has reached 17.3 million, most living in resource-poor settings, interest has grown in identifying and evaluating appropriate care arrangements for them. In this study, we describe the community-based family-style group homes ('group homes') in rural China. Guided by an ecological framework of children's wellbeing, we conducted a series of ethnographic observations, in-depth interviews and group discussions in the rural areas of Henan Province, which has been severely impacted by the AIDS endemic through commercial blood collection. Based on our observations and discussions, group homes appear to provide stable and safe living environments for children orphaned by AIDS. Adequate financial support from non-government organizations (NGOs) as well as the central and provincial governments has ensured a low child-caregiver ratio and attention to the basic needs of the children at group homes. The foster parents were selected from the local community and appear to have adequate qualifications and dedication. They receive a monthly stipend, periodical evaluation and parenting consultation from supporting NGOs. The foster parents and children in the group homes have formed strong bonds. Both children and foster parents reported positively on health and education. Characteristics of community-based group homes can be replicated in other care arrangements for AIDS orphans in resource poor settings for the optimal health outcomes of those vulnerable children. We also call for capacity building for caregivers and communities to provide sustainable and supportive living environment for these children. PMID- 25124084 TI - African stakeholders' views of research options to improve nutritional status in sub-Saharan Africa. AB - BACKGROUND: Setting research priorities for improving nutrition in Africa is currently ad hoc and there is a need to shift the status quo in the light of slow progress in reducing malnutrition. This study explored African stakeholders' views on research priorities in the context of environmental and socio demographic changes that will impact on nutritional status in Africa in the coming years. METHODS: Using Multi-Criteria Mapping, quantitative and qualitative data were gathered from 91 stakeholders representing 6 stakeholder groups (health professionals, food Industry, government, civil society, academics and research funders) in Benin, Mozambique, South Africa, Tanzania, Togo and Uganda. Stakeholders appraised six research options (ecological nutrition, nutritional epidemiology, community nutrition interventions, behavioural nutrition, clinical nutrition and molecular nutrition) for how well they could address malnutrition in Africa. RESULTS: Impact (28.3%), research efficacy (23.6%) and social acceptability (22.4%) were the criteria chosen the most to evaluate the performance of research options. Research on the effectiveness of community interventions was seen as a priority by stakeholders because they were perceived as likely to have an impact relatively quickly, were inexpensive and cost effective, involved communities and provided direct evidence of what works. Behavioural nutrition research was also highly appraised. Many stakeholders, particularly academics and government were optimistic about the value of ecological nutrition research (the impact of environmental change on nutritional status). Research funders did not share this enthusiasm. Molecular nutrition was least preferred, considered expensive, slow to have an impact and requiring infrastructure. South Africa ranked clinical and molecular nutrition the highest of all countries. CONCLUSION: Research funders should redirect research funds in Africa towards the priorities identified by giving precedence to develop the evidence for effective community nutrition interventions. Expanding research funding in behavioural and ecological nutrition was also valued and require multi disciplinary collaborations between nutritionists, social scientists, agricultural and climate change scientists. PMID- 25124086 TI - The role of environmental context, faith, and patient satisfaction in HIV prevention among African American women. PMID- 25124085 TI - Asymmetric gold-catalyzed lactonizations in water at room temperature. AB - Asymmetric gold-catalyzed hydrocarboxylations are reported that show broad substrate scope. The hydrophobic effect associated with in situ-formed aqueous nanomicelles gives good to excellent ee's of product lactones. In-flask product isolation, along with the recycling of the catalyst and the reaction medium, are combined to arrive at an especially environmentally friendly process. PMID- 25124087 TI - Posttraumatic disease of the palmar fascia. PMID- 25124088 TI - Peripheral nerve injuries: advancing the field through research, collaboration, and education. AB - The Andrew J. Weiland Medal is presented each year by the American Society for Surgery of the Hand and the American Foundation for Surgery of the Hand for a body of work related to hand surgery research. This essay, awarded the Weiland Medal in 2013, focuses on advancing the field of peripheral nerve injuries through research, collaboration, and education. PMID- 25124089 TI - Identifying optimal biomarker combinations for treatment selection via a robust kernel method. AB - Treatment-selection markers predict an individual's response to different therapies, thus allowing for the selection of a therapy with the best predicted outcome. A good marker-based treatment-selection rule can significantly impact public health through the reduction of the disease burden in a cost-effective manner. Our goal in this article is to use data from randomized trials to identify optimal linear and nonlinear biomarker combinations for treatment selection that minimize the total burden to the population caused by either the targeted disease or its treatment. We frame this objective into a general problem of minimizing a weighted sum of 0-1 loss and propose a novel penalized minimization method that is based on the difference of convex functions algorithm (DCA). The corresponding estimator of marker combinations has a kernel property that allows flexible modeling of linear and nonlinear marker combinations. We compare the proposed methods with existing methods for optimizing treatment regimens such as the logistic regression model and the weighted support vector machine. Performances of different weight functions are also investigated. The application of the proposed method is illustrated using a real example from an HIV vaccine trial: we search for a combination of Fc receptor genes for recommending vaccination in preventing HIV infection. PMID- 25124090 TI - Norwegian nursing and medical students' perception of interprofessional teamwork: a qualitative study. AB - BACKGROUND: Little is known about the ways in which nursing and medical students perceive and understand their roles in interprofessional teamwork. A 2010 report by the World Health Organization highlights the importance of students' understanding of teamwork in healthcare, and their ability to be effective team players. This study aims at describing nursing and medical students' perceptions of interprofessional teamwork, focusing on experiences and recommendations that can be used to guide future educational efforts. METHODS: The study uses a qualitative research design. Data were collected from four focus group interviews: two homogenous groups (one with medical students, one with nursing students) and two mixed groups (medical and nursing students). RESULTS: The results show that traditional patterns of professional role perception still prevail and strongly influence students' professional attitudes about taking responsibility and sharing responsibility across disciplinary and professional boundaries. It was found that many students had experienced group cultures detrimental to team work. Focusing on clinical training, the study found a substantial variation in perception with regard to the different arenas for interprofessional teamwork, ranging from arenas with collaborative learning to arenas characterized by distrust, confrontation, disrespect and hierarchical structure. CONCLUSIONS: This study underlines the importance of a stronger focus on interprofessional teamwork in health care education, particularly in clinical training. The study results suggest that the daily rounds and pre-visit "huddles," or alternatively psychiatric wards, offer arenas suitable for interprofessional training, in keeping with the students' assessments and criteria proposed in previous studies. PMID- 25124091 TI - Voiding diaries: adherence in the clinical setting. AB - INTRODUCTION AND HYPOTHESIS: The objective was to document adherence with 24-h voiding diaries in the evaluation of routine urogynecology patients. METHODS: This was a cross-sectional study of 200 patients presenting for initial urogynecological consultation. All were mailed a standardized packet prior to their visit, including a 24-h voiding diary. Upon arrival, subjects were asked to complete a brief survey. Eight questions targeted those that completed the diary ("completers"); 3 targeted those that did not ("noncompleters"). "Completers" were further sub-classified based on survey responses. Those recording each void immediately were termed "appropriate completers." Others were considered "inappropriate completers." Demographics and other data were obtained from the medical records. RESULTS: Eleven women were excluded for recording more than 24 h of data. Of the 189 remaining subjects, 157 (83 %) completed the diary. Many "noncompleters" were unaware of the diary (54 %). Others chose not to complete it, most commonly citing "don't think it applies" (25 %). On univariate analysis "completers" were older (p = 0.049), with more complaints of mixed incontinence (p = 0.001). Fifty-four percent of "completers" were deemed "appropriate." "Appropriate completers" voided more frequently (p = 0.024) than "inappropriate completers." After multivariate analyses, however, only lower parity and unemployed status were associated with appropriate diary completion. Reassuringly, the majority, 77 %, believed that the diary responses were reflective of their typical behavior, and voiding frequency on the diary correlated with self-report during their medical history (rs = 0.483, p < 0.001). CONCLUSIONS: Although compliance with voiding diaries is reasonably high in the office setting, adherence to instructions is less optimal. Strategies to improve ease of use could benefit future patient care. PMID- 25124092 TI - Pelvic organ prolapse surgical management in Portugal and FDA safety communication have an impact on vaginal mesh. AB - INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) surgery has lately gained importance in gynecological practice. This study aims to characterize the evolution of POP surgical procedures conducted in Portugal in the last decade and the impact of an FDA 2011 safety communication on mesh POP surgeries. METHODS: Trends in the surgical management of POP were assessed using the Portuguese National Medical Registry. We considered all records of women with diagnosis of genital prolapse from 1 January 2000 to 31 December 2012. Additionally, we also conducted a survey among members of the Portuguese Society of Urogynecology to evaluate current practices in the surgical management of POP. RESULTS: From 2000 to 2012, 46,819 diagnoses of genital prolapse were registered, with a 105 % increase during the study period (2,368 in 2000 to 4,941 in 2012). POP mesh surgery represented only 6 % of total prolapse diagnoses, but mesh use greatly increased up to 2011, when only a slight increase was registered. Among gynecologists who responded to the questionnaire, there was considerable variability on the procedures of choice to treat POP. Fifty-seven per cent of respondents performed vaginal mesh POP surgery, but only 27 % of those actually reported having changed their practice after the FDA 2011 safety communication. CONCLUSIONS: Surgical procedures for POP conducted in Portugal greatly increased over the last decade. The use of surgical meshes is still limited, but despite FDA safety communication it has increased over the years, with a slight increase in 2012, which illustrates the need for further analyses in the coming years. PMID- 25124093 TI - The genetic control of aposematic black pigmentation in hemimetabolous insects: insights from Oncopeltus fasciatus. AB - Variations in body pigmentation, encompassing both the range of specific colors as well as the spatial arrangement of those colors, are among the most noticeable and lineage-specific insect features. However, the genetic mechanisms responsible for generating this diversity are still limited to several model species that are primarily holometabolous insects. To address this lack of knowledge, we utilize Oncopeltus fasciatus, an aposematic hemimetabolous insect, as a new model to study insect pigmentation. First, to determine the genetic regulation of black pigment production in Oncopeltus, we perform an RNAi analysis on three core genes involved in the melanin pathway, tyrosine hydroxylase (TH), dopa decarboxylase (DDC), and laccase 2 (lac2). The black pigmentation is affected in all instances, showing that the black pigments in this species are derived from the melanin pathway. The results of the DDC RNAi are particularly informative because they reveal that it is Dopamine melanin, not DOPA melanin, which is the predominant component of black pigments in Oncopeltus. Second, we test whether pigmentation follows a two-step model where the spatial pre-mapping of enzymatic activity is followed by vein-dependent transportation of melanin substances. We confirm the existence of the first step by observing that premature wings develop black pigmentation when exposed to melanin precursors. In addition, we provide evidence for the second step by showing that wing melanin patterning is disrupted when vein transportation is halted. These findings bring novel insights from a hemimetabolous species and establish a framework for subsequent studies on the mechanisms of pigment production and patterning responsible for variations in insect coloration. PMID- 25124094 TI - Regulatory volume increase in astrocytes exposed to hypertonic medium requires beta1 -adrenergic Na(+) /K(+) -ATPase stimulation and glycogenolysis. AB - The cotransporter of Na(+) , K(+) , 2Cl(-) , and water, NKKC1, is activated under two conditions in the brain, exposure to highly elevated extracellular K(+) concentrations, causing astrocytic swelling, and regulatory volume increase in cells shrunk in response to exposure to hypertonic medium. NKCC1-mediated transport occurs as secondary active transport driven by Na(+) /K(+) -ATPase activity, which establishes a favorable ratio for NKCC1 operation between extracellular and intracellular products of the concentrations of Na(+) , K(+) , and Cl(-) * Cl(-) . In the adult brain, astrocytes are the main target for NKCC1 stimulation, and their Na(+) /K(+) -ATPase activity is stimulated by elevated K(+) or the beta-adrenergic agonist isoproterenol. Extracellular K(+) concentration is normal during regulatory volume increase, so this study investigated whether the volume increase occurred faster in the presence of isoproterenol. Measurement of cell volume via live cell microscopic imaging fluorescence to record fluorescence intensity of calcein showed that this was the case at isoproterenol concentrations of >=1 uM in well-differentiated mouse astrocyte cultures incubated in isotonic medium with 100 mM sucrose added. This stimulation was abolished by the beta1 -adrenergic antagonist betaxolol, but not by ICI118551, a beta2 -adrenergic antagonist. A large part of the beta1 adrenergic signaling pathway in astrocytes is known. Inhibitors of this pathway as well as the glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol hydrochloride and the NKCC1 inhibitors bumetanide and furosemide abolished stimulation by isoproterenol, and it was weakened by the Na(+) /K(+) -ATPase inhibitor ouabain. These observations are of physiological relevance because extracellular hypertonicity occurs during intense neuronal activity. This might trigger a regulatory volume increase, associated with the post-excitatory undershoot. PMID- 25124095 TI - Relationship between mid-trimester ultrasound fetal liver length measurements and gestational diabetes mellitus. AB - BACKGROUND: The aim of the present study was to investigate the relationship between mid-trimester ultrasound fetal liver length (FLL) and gestational diabetes mellitus (GDM) in a high-risk population. METHODS: A prospective study was performed in 331 women with singleton pregnancies who were at high risk of GDM and were undergoing a mid-trimester ultrasound examination. The ultrasound scan at 23 weeks gestation was followed by a 100-g oral glucose tolerance test (OGTT) at 24 weeks gestation. Correlations between FLL and OGTT results at different time points were tested. Receiver operating characteristic (ROC) analysis of FLL as a potential prognostic factor for GDM was also performed. RESULTS: In GDM patients, there was a significant positive correlation (P < 0.01) between FLL and OGTT glycemia immediately before and 60, 120, and 180 min after glucose intake. Mean FLL in GDM was significantly higher than in healthy subjects (41.04 vs 31.09 mm, respectively; P < 0.001). When tested as a potential prognostic factor for GDM, fetal liver measurements showed excellent diagnostic performance. The ROC analysis established a cut-off value of FLL of 39 mm for the prediction GDM, with sensitivity of 71.76%, specificity 97.56%, positive predictive value 91.0%, and negative predictive value 90.9%. The usefulness of FLL measurements was supported by a high area under the ROC curve (90.5%). CONCLUSION: In conclusion, there is a strong correlation between FLL and OGTT results, with FLL possibly serving as a valid marker for the prediction of GDM in high-risk populations. PMID- 25124096 TI - A transcriptome approach to ecdysozoan phylogeny. AB - The monophyly of Ecdysozoa, which comprise molting phyla, has received strong support from several lines of evidence. However, the internal relationships of Ecdysozoa are still contended. We generated expressed sequence tags from a priapulid (penis worm), a kinorhynch (mud dragon), a tardigrade (water bear) and five chelicerate taxa by 454 transcriptome sequencing. A multigene alignment was assembled from 63 taxa, which comprised after matrix optimization 24,249 amino acid positions with high data density (2.6% gaps, 19.1% missing data). Phylogenetic analyses employing various models support the monophyly of Ecdysozoa. A clade combining Priapulida and Kinorhyncha (i.e. Scalidophora) was recovered as the earliest branch among Ecdysozoa. We conclude that Cycloneuralia, a taxon erected to combine Priapulida, Kinorhyncha and Nematoda (and others), are paraphyletic. Rather Arthropoda (including Onychophora) are allied with Nematoda and Tardigrada. Within Arthropoda, we found strong support for most clades, including monophyletic Mandibulata and Pancrustacea. The phylogeny within the Euchelicerata remained largely unresolved. There is conflicting evidence on the position of tardigrades: While Bayesian and maximum likelihood analyses of only slowly evolving genes recovered Tardigrada as a sister group to Arthropoda, analyses of the full data set, and of subsets containing genes evolving at fast and intermediate rates identified a clade of Tardigrada and Nematoda. Notably, the latter topology is also supported by the analyses of indel patterns. PMID- 25124097 TI - Evolutionary relationships in the medicinally important genus Fritillaria L. (Liliaceae). AB - Fritillaria (Liliaceae) is a genus of approximately 140 species of bulbous perennial plants that includes taxa of both horticultural and medicinal importance. As well as being commercially valuable, Fritillaria species have attracted attention because of their exceptionally large genome sizes, with all values recorded to date in excess of 30Gb. Despite such interest in the genus, phylogenetic relationships between the majority of species have remained untested. Here we present the first phylogenetic reconstruction of relationships to encompass most of the currently recognised species diversity in the genus. Three regions of the plastid genome were sequenced in 117 individuals of Fritillaria, representing 92 species (c. 66% of the genus) and in representatives of nine other genera of Liliaceae. Eleven low-copy nuclear gene regions were also screened in selected species for their potential utility. Phylogenetic analysis of a combined plastid dataset using maximum parsimony and Bayesian inference provided support for the monophyly of the majority of currently recognised subgenera. However, subgenus Fritillaria, which is by far the largest of the subgenera and includes the most important species used in traditional Chinese medicine, is found to be polyphyletic. Moreover, several taxa that were represented by multiple individuals show evidence of species non-monophyly. The Japanese endemic subgenus Japonica, which contains the species with the largest recorded genome size for any diploid plant, is resolved as sister to the predominantly Middle Eastern and Central Asian subgenus Rhinopetalum. Whilst relationships between most of the major Fritillaria lineages can now be resolved, our results also highlight the need for data from additional independently evolving loci; an endeavour that may be particularly challenging in light of the huge nuclear genomes found in these plants. PMID- 25124098 TI - Should genes with missing data be excluded from phylogenetic analyses? AB - Phylogeneticists often design their studies to maximize the number of genes included but minimize the overall amount of missing data. However, few studies have addressed the costs and benefits of adding characters with missing data, especially for likelihood analyses of multiple loci. In this paper, we address this topic using two empirical data sets (in yeast and plants) with well-resolved phylogenies. We introduce varying amounts of missing data into varying numbers of genes and test whether the benefits of excluding genes with missing data outweigh the costs of excluding the non-missing data that are associated with them. We also test if there is a proportion of missing data in the incomplete genes at which they cease to be beneficial or harmful, and whether missing data consistently bias branch length estimates. Our results indicate that adding incomplete genes generally increases the accuracy of phylogenetic analyses relative to excluding them, especially when there is a high proportion of incomplete genes in the overall dataset (and thus few complete genes). Detailed analyses suggest that adding incomplete genes is especially helpful for resolving poorly supported nodes. Given that we find that excluding genes with missing data often decreases accuracy relative to including these genes (and that decreases are generally of greater magnitude than increases), there is little basis for assuming that excluding these genes is necessarily the safer or more conservative approach. We also find no evidence that missing data consistently bias branch length estimates. PMID- 25124099 TI - Selective adsorption of metoprolol enantiomers using 2-hydroxypropyl-beta cyclodextrin cross-linked multiwalled carbon nanotube. AB - This study investigates the ability of functionalized multiwalled carbon nanotubes (MWCNTs) for enantio-separation of metoprolol chiral forms. 2Hydroxypropyl-beta-cyclodextrin (2HP-beta-CD) was applied as a chiral selector to functionalize carbon nanotubes (CNTs). The modified multiwalled CNT samples were characterized using scanning electron microscopy and Fourier transform infrared spectroscopy. The results of analyses showed that CNTs were successfully cross-linked with 2HP-beta-CD. To evaluate the enantio-separation property of the products, the separation of metoprolol chiral forms on the initial and final products was examined. Further, UV-visible spectroscopy and polarimeter analyses were used for characterization. The results indicate that MWCNT does not have any intrinsic enantio-separation ability, although its selectivity for enantio separation can be enhanced by cross-linking it to 2HP-beta-CD. Moreover, the optimal mass of adsorbent as well as optimal mass of functional groups is estimated to achieve maximum enantio-separation efficiency. The results indicate that applying large amounts of 2HP-beta-CD to CNTs functionalization decreases the cross-linking efficiency, which consequently reduces enantio-separation efficiency. PMID- 25124100 TI - The advantage of professional organizations as advocates for improved funding of maternal and child health services in Uganda. AB - The attainment of United Nations Millennium Development Goal 5 has proven elusive for many countries. Efforts to reduce maternal mortality require concerted evidence-based efforts from all key players, including professional organizations. The Association of Obstetricians and Gynaecologists of Uganda used the results of maternal and perinatal death review to develop and pilot advocacy programs with parliamentarians, media, and government that aimed to improve maternal and newborn health in Uganda. This work translated to further parliamentary debate on the topic, increased resource allocation by government, and improved media-related public education. PMID- 25124101 TI - One-year evaluation of the impact of an emergency obstetric and neonatal care training program in Western Kenya. AB - OBJECTIVE: To determine the impact of introducing an emergency obstetric and neonatal care training program on maternal and perinatal morbidity and mortality at Moi Teaching and Referral Hospital, Eldoret, Kenya. METHODS: A prospective chart review was conducted of all deliveries during the 3-month period (November 2009 to January 2010) before the introduction of the Advances in Labor and Risk Management International Program (AIP), and in the 3-month period (August November 2011) 1 year after the introduction of the AIP. All women who were admitted and delivered after 28 weeks of pregnancy were included. The primary outcome was the direct obstetric case fatality rate. RESULTS: A total of 1741 deliveries occurred during the baseline period and 1812 in the postintervention period. Only one mother died in each period. However, postpartum hemorrhage rates decreased, affecting 59 (3.5%) of 1669 patients before implementation and 40 (2.3%) of 1751 afterwards (P=0.029). The number of patients who received oxytocin increased from 829 (47.6%) to 1669 (92.1%; P<0.001). Additionally, the number of neonates with 5-minute Apgar scores of less than 5 reduced from 133 (7.7%) of 1717 to 95 (5.4%) of 1745 (P=0.006). CONCLUSION: The introduction of the AIP improved maternal outcomes. There were significant differences related to use of oxytocin and postpartum hemorrhage. PMID- 25124102 TI - A chromosomal 5q31.1 gain involving PITX1 causes Liebenberg syndrome. PMID- 25124103 TI - Increased blood glucose is related to disturbed cerebrovascular pressure reactivity after traumatic brain injury. AB - BACKGROUND: Increased blood glucose and impaired pressure reactivity (PRx) after traumatic brain injury (TBI) are both known to correlate with unfavorable patient outcome. However, the relationship between these two variables is unknown. METHODS: To test the hypothesis that increased blood glucose leads to increased PRx, we retrospectively analyzed data from 86 traumatic brain injured patients admitted to the Neurocritical Care Unit. Data analyzed included arterial glucose concentration, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and end-tidal CO2. PRx was calculated as the moving correlation coefficient between averaged (10 seconds) arterial blood pressure and ICP. One arterial glucose concentration and one time-aligned PRx value were obtained for each patient, during each day until the fifth day after ictus. RESULTS: Mean arterial glucose concentrations during the first 5 days since ictus were positively correlated with mean PRx (Pearson correlation coefficient = 0.25, p = 0.02). The correlation was strongest on the first day after injury (Pearson correlation coefficient = 0.47, p = 0.008). CONCLUSION: Our preliminary findings indicate that increased blood glucose may impair cerebrovascular reactivity, potentially contributing to a mechanistic link between increased blood glucose and poorer outcome after TBI. PMID- 25124104 TI - Plasmapheresis may be an option in urgent management of heparin-induced thrombocytopenia in the setting of acute intracerebral hemorrhage. AB - BACKGROUND: We report a case of heparin-induced thrombocytopenia (HIT) that was complicated by acute intracerebral hemorrhage (ICH) and bilateral adrenal hemorrhage. In the setting of worsening thrombocytopenia, the risk of expansion of ICH and additional thrombotic events is concerning; hence, we employed plasmapheresis to reduce thrombotic risk. METHODS: We followed serial daily heparin antibody enzyme-linked immunosorbent assay (ELISA) optical density measurements as well as heparin-induced platelet aggregation (HIPA) assays on both pre- and post-pheresis samples in order to objectively determine when thrombotic risk was sufficiently decreased. RESULTS: After four cycles of plasmapheresis, both heparin antibody ELISA and HIPA assays became negative. CONCLUSION: This case helps illustrate the utility of plasmapheresis in management of HIT when anticoagulation is contraindicated. PMID- 25124106 TI - Ventriculostomy-Associated Infection (VAI): In Search of a Definition. PMID- 25124105 TI - Accuracy of nimodipine gel extraction. AB - INTRODUCTION: Until recently, use of nimodipine in aneurysmal subarachnoid hemorrhage patients unable to swallow required extraction of gel from inside the commercially available capsule. Despite the Black-Box warning against inadvertent intravenous administration, bedside extraction of the gel from the capsule continues to be a common practice in some institutions. The accuracy of bedside extraction has not been formally evaluated. METHODS: Twenty-eight nurses from the neurology and neurosurgical ICUs at a single center attempted to extract nimodipine gel from 2 capsules, each using the method currently approved by the US FDA. The primary outcome was mean weight of extracted gel per capsule, which was compared to both gel weight from batch compounded pharmacy syringes and a pre calculated appropriate weight for 30 mg nimodipine gel. RESULTS: Simulated bedside extraction provided lower yield than pharmacy-compounded syringes (22.6 +/- 4.6 mg vs 30.4 +/- 0.59 mg, p = 0.001). Bedside extraction provided inconsistent and low yield (75.4 +/- 15.32 % of possible dose extracted, p = 0.0001 for comparison of means between bedside extraction syringes and predicted gel weight). Pharmacy-compounded syringes provided consistent high yield (101.3 +/- 2.0 % of possible dose extracted, p = 0.14 for comparison of means between pharmacy syringes and predicted gel weight). CONCLUSION: Combined with reports of significant patient harm and death with inadvertent intravenous administration, this study suggests that there is no role for bedside extraction of nimodipine in clinical practice. PMID- 25124107 TI - Prostate cancer mortality outcomes and patterns of primary treatment for Aboriginal men in New South Wales, Australia. AB - OBJECTIVE: To compare prostate cancer mortality for Aboriginal and non-Aboriginal men and to describe prostate cancer treatments received by Aboriginal men. PATIENTS AND METHODS: We analysed cancer registry records for all men diagnosed with prostate cancer in New South Wales (NSW) in 2001-2007 linked to hospital inpatient episodes and deaths. More detailed information on androgen-deprivation therapy and radiotherapy was obtained from medical records for 87 NSW Aboriginal men diagnosed in 2000-2011. The main outcomes were primary treatment for, and death from, prostate cancer. Analysis included Cox proportional hazards regression and logistic regression. RESULTS: There were 259 Aboriginal men among 35,214 prostate cancer cases diagnosed in 2001-2007. Age and spread of disease at diagnosis were similar for Aboriginal and non-Aboriginal men. Prostate cancer mortality 5 years after diagnosis was higher for Aboriginal men (17.5%, 95% confidence interval (CI) 12.4-23.3) than non-Aboriginal men (11.4%, 95% CI 11.0 11.8). Aboriginal men were 49% more likely to die from prostate cancer (hazard ratio 1.49, 95% CI 1.07-1.99) after adjusting for differences in demographic factors, stage at diagnosis, health access and comorbidities. Aboriginal men were less likely to have a prostatectomy for localised or regional cancer than non Aboriginal men (adjusted odds ratio 0.60, 95% CI 0.40-0.91). Of 87 Aboriginal men with full staging and treatment information, 60% were diagnosed with localised disease. Of these, 38% had a prostatectomy (+/- radiotherapy), 29% had radiotherapy only and 33% had neither. CONCLUSION: More research is required to explain differences in treatment and mortality for Aboriginal men with prostate cancer compared with non-Aboriginal men. In the meantime, ongoing monitoring and efforts are needed to ensure Aboriginal men have equitable access to best care. PMID- 25124109 TI - Strong anisotropic dynamics of ultra-confined water. AB - Dynamics of water confined in ~5 A diameter channels of beryl and cordierite single crystals were studied by using inelastic (INS) and quasielastic (QENS) neutron scattering. The INS spectra for both samples were similar and showed that there are no hydrogen bonds acting on water molecule, which experiences strong anisotropic potential, steep along the channels and very soft perpendicular to it. The high-resolution (3.4 MUeV) QENS data revealed gradual freezing out of the water molecule dynamics for both minerals at temperatures below about 80 K when the scattering momentum transfer was parallel to the channels, but not when it was perpendicular to the channels. The QENS study with medium energy resolution (0.25 meV) of the beryl with the scattering momentum transfer along the channels showed gradual freezing out of water molecule dynamics at temperatures below about 200 K, whereas at higher temperatures the data could be described as 2-fold rotational jumps about the axis coinciding with the direction of the dipole moment (that is, perpendicular to the channels), with a residence time of 5.5 ps at 225 K. The energy resolution dependence of the apparent dynamics freezing temperature suggests gradual slowing down of the rotational jumps as the temperature is decreased, until the associated QENS broadening can no longer be detected, rather than actual freezing. PMID- 25124108 TI - CRF-based models of protein surfaces improve protein-protein interaction site predictions. AB - BACKGROUND: The identification of protein-protein interaction sites is a computationally challenging task and important for understanding the biology of protein complexes. There is a rich literature in this field. A broad class of approaches assign to each candidate residue a real-valued score that measures how likely it is that the residue belongs to the interface. The prediction is obtained by thresholding this score.Some probabilistic models classify the residues on the basis of the posterior probabilities. In this paper, we introduce pairwise conditional random fields (pCRFs) in which edges are not restricted to the backbone as in the case of linear-chain CRFs utilized by Li et al. (2007). In fact, any 3D-neighborhood relation can be modeled. On grounds of a generalized Viterbi inference algorithm and a piecewise training process for pCRFs, we demonstrate how to utilize pCRFs to enhance a given residue-wise score-based protein-protein interface predictor on the surface of the protein under study. The features of the pCRF are solely based on the interface predictions scores of the predictor the performance of which shall be improved. RESULTS: We performed three sets of experiments with synthetic scores assigned to the surface residues of proteins taken from the data set PlaneDimers compiled by Zellner et al. (2011), from the list published by Keskin et al. (2004) and from the very recent data set due to Cukuroglu et al. (2014). That way we demonstrated that our pCRF based enhancer is effective given the interface residue score distribution and the non-interface residue score are unimodal.Moreover, the pCRF-based enhancer is also successfully applicable, if the distributions are only unimodal over a certain sub-domain. The improvement is then restricted to that domain. Thus we were able to improve the prediction of the PresCont server devised by Zellner et al. (2011) on PlaneDimers. CONCLUSIONS: Our results strongly suggest that pCRFs form a methodological framework to improve residue-wise score-based protein protein interface predictors given the scores are appropriately distributed. A prototypical implementation of our method is accessible at http://ppicrf.informatik.uni-goettingen.de/index.html. PMID- 25124110 TI - Development of the Japanese version of the Minneapolis-Manchester Quality of Life Survey of Health - Adolescent Form (MMQL-AF) and investigation of its reliability and validity. AB - BACKGROUND: There are very few reliable and valid measures in Japan assessing health-related quality of life (HRQOL) in children with cancer. The present study aimed to develop a Japanese version of the Minneapolis-Manchester Quality of Life Survey of Health Adolescent Form (MMQL-AF), which is a measure for assessing the HRQOL of childhood cancer survivors, and investigate its reliability and validity. METHODS: Participants were 141 children with cancer who had been off therapy for more than one year and 183 healthy controls. The reliability and internal consistency of the measure were assessed through test-retest methods using Cronbach's coefficient alpha and intra-class correlation coefficients (ICCs). For validation of the measure, factorial validity, concurrent validity using the Japanese version of PedsQL 4.0 Generic Core Scales (PedsQL-J), and discriminant validity using comparisons between children with cancer and healthy controls were investigated. RESULTS: Of the 46 items in the original version, 44 items were determined to comprise the Japanese version of the MMQL-AF. Cronbach's coefficient alphas for each subscale were high ranging from 0.83 to 0.89. Test retest reliability ranged between ICC 0.79 to 0.96. Investigation of concurrent validity using the PedsQL-J demonstrated strong correlations in physical functions and moderate correlations for other factors. A significant difference was observed between children with cancer and healthy controls. CONCLUSIONS: Thus, the Japanese version of the MMQL-AF served as a self-evaluation questionnaire that allowed for practical, comprehensive, and multidimensional measurement of HRQOL specific to childhood cancer survivors. PMID- 25124111 TI - Electrochemical synthesis on nanoparticle chains to couple semiconducting rods: coulomb blockade modulation using photoexcitation. AB - Hybrid nanostructures are made by coupling a room temperature coulomb blockade device with photoexcitable nano-rods. Direct electrochemical synthesis on nanoparticle chain arrays leads to the formation of semiconducting rods that are in direct contact with the nanoparticles and also spatial confined by them. This direct interfacing leads to mutual intermodulation between the two systems. PMID- 25124112 TI - Synthesis and biological evaluation of novel thiadiazole amides as potent Cdc25B and PTP1B inhibitors. AB - A series of novel thiadiazole amide derivatives have been synthesized and evaluated for inhibitory activities against Cdc25B and PTP1B. Most of them showed inhibitory activities against Cdc25B (IC50=1.18-8.01 MUg/mL) and PTP1B (IC50=0.85 8.75 MUg/mL), respectively. Moreover, compounds 5b and 4l were most potent with IC50 values of 1.18 and 0.85 MUg/mL for Cdc25B and PTP1B, respectively, compared with reference drugs Na3VO4 (IC50=0.93 MUg/mL) and oleanolic acid (IC50=0.85 MUg/mL). The results of selectivity experiments showed that the target compounds were selective inhibitors against PTP1B and Cdc25B. Enzyme kinetic experiments demonstrated that compound 5k was a specific inhibitor with the typical characteristics of a mixed inhibitor. PMID- 25124113 TI - Cytotoxic activity of butane type of 1,7-seco-2,7'-cyclolignanes and apoptosis induction by Caspase 9 and 3. AB - All stereoisomers of methoxybutane and fluorobutane type of 1,7-seco-2,7' cyclolignane were synthesized and cytotoxic activities of these compounds were compared with those of all stereoisomers of butane and butanol type compounds. Both enantiomers of butane type secocyclolignane showed higher cytotoxic activity (IC50=16-20 MUM) than methoxy type compounds, whereas none was observed for all the stereoisomers of butanol type secocyclolignane, however, (-)-Kadangustin J showed stereospecific cytotoxic activity (IC50=47-67 MUM). Since (R)-9'-fluoro derivative 23 was most potent (IC50=19 MUM) among the corresponding fluoro stereoisomers, (R)-9'-alkyl derivatives were synthesized, hydrophobic 9'-heptyl derivative 27 showing highest activity (IC50=3.7 MUM against HL-60, IC50=3.1 MUM against HeLa) in this experiment. Apoptosis induction caused by Caspase 3 and 9 for (R)-9'-heptyl derivative 27 was observed in the research on the mechanism. A degradation of DNA into small fragments was also shown by DNA ladder assay. PMID- 25124114 TI - Phorbaketals L-N, cytotoxic sesterterpenoids isolated from the marine sponge of the genus Phorbas. AB - Three new sesterterpenoids, phorbaketals L-N (1-3), were isolated from a marine sponge of the genus Phorbas and their complete structures were elucidated via analysis of HRFABMS and NMR spectroscopic data. Phorbaketal N (3) showed potent cytotoxicity against human pancreas cancer cells (IC50=11.4 MUM). PMID- 25124116 TI - 4-Substituted quinazoline derivatives as novel EphA2 receptor tyrosine kinase inhibitors. AB - Erythropoietin-producing hepatocellular receptor tyrosine kinase subtype A2 (EphA2) is an attractive therapeutic target for suppressing tumor progression. In our efforts to discover novel small molecules to inhibit EphA2, a class of compound based on 4-substituted quinazoline containing 7-(morpholin-2-ylmethoxy) group was identified as a novel hit by high throughput screening campaign. Structural modification of parent quinazoline scaffolds by introducing substituents on aniline displayed potent inhibitory activities toward EphA2. PMID- 25124115 TI - Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1. AB - We report the discovery and characterization of a series of benzoisothiazolone inhibitors of PHOSPHO1, a newly identified soluble phosphatase implicated in skeletal mineralization and soft tissue ossification abnormalities. High throughput screening (HTS) of a small molecule library led to the identification of benzoisothiazolones as potent and selective inhibitors of PHOSPHO1. Critical structural requirements for activity were determined, and the compounds were subsequently derivatized and measured for in vitro activity and ADME parameters including metabolic stability and permeability. On the basis of its overall profile the benzoisothiazolone analogue 2q was selected as MLPCN probe ML086. PMID- 25124118 TI - Affective and cognitive determinants of women's sexual response to erotica. AB - INTRODUCTION: The specific cognitive-affective mechanisms involved in the activation and regulation of the subjective and genital components of sexual arousal are not fully understood yet. AIM: The aim of the present study was to investigate the contribution of self-reported thoughts and affect to the prediction of women's subjective and genital responses to erotica. METHODS: Twenty-eight sexually functional women (mean age = 32, SD = 6.29) were presented with sexually explicit and nonexplicit romantic films. Genital responses, subjective sexual arousal, state affect, and self-reported thoughts were assessed. MAIN OUTCOME MEASURES: Vaginal pulse amplitude was measured using a vaginal photoplethysmograph. Subjective sexual arousal, thoughts, and affective responses were assessed through self-report scales. RESULTS: Correlations between subjective and physiological sexual arousal were low (r = -0.05, P > 0.05). Self reported thoughts and affect were significant predictors of subjective sexual arousal. The strongest single predictor of subjective arousal was sexual arousal thoughts (e.g., "I'm getting excited") (beta = 0.63, P < 0.01). None of the cognitive or affective variables predicted women's genital responses. CONCLUSIONS: Overall, results support the role of cognitive (self-reported thoughts) and affective dimensions in women's subjective sexual arousal to erotica and, consistent with previous findings, suggest that subjective and physiological sexual arousal may be impacted by different processes. PMID- 25124117 TI - Complotype affects the extent of down-regulation by Factor I of the C3b feedback cycle in vitro. AB - Sera from a large panel of normal subjects were typed for three common polymorphisms, one in C3 (R102G) and two in Factor H (V62I and Y402H), that influence predisposition to age-related macular degeneration and to some forms of kidney disease. Three groups of sera were tested; those that were homozygous for the three risk alleles; those that were heterozygous for all three; and those homozygous for the low-risk alleles. These groups vary in their response to the addition of exogenous Factor I when the alternative complement pathway is activated by zymosan. Both the reduction in the maximum amount of iC3b formed and the rate at which the iC3b is converted to C3dg are affected. For both reactions the at-risk complotype requires higher doses of Factor I to produce similar down regulation. Because iC3b reacting with the complement receptor CR3 is a major mechanism by which complement activation gives rise to inflammation, the breakdown of iC3b to C3dg can be seen to have major significance for reducing complement-induced inflammation. These findings demonstrate for the first time that sera from subjects with different complement alleles behave as predicted in an in-vitro assay of the down-regulation of the alternative complement pathway by increasing the concentration of Factor I. These results support the hypothesis that exogenous Factor I may be a valuable therapeutic aid for down-regulating hyperactivity of the C3b feedback cycle, thereby providing a treatment for age related macular degeneration and other inflammatory diseases of later life. PMID- 25124119 TI - An open trial of group metacognitive therapy for depression in Norway. AB - BACKGROUND: Preliminary data support the implementation of individual metacognitive therapy (MCT) for depression. Given the focus of MCT on transpersonal processes, we hypothesized that this treatment should translate well to a group format. In this study, the effects and feasibility associated with group MCT for depression are reported. METHODS: Eleven patients who were consecutively referred by general practitioners to a specialist psychiatric practice in Norway participated in an open trial of the effects and feasibility associated with group MCT for depression. All of the patients met the DSM-IV criteria for major depressive disorder (MDD) and were monitored in a baseline period before attending 90-min weekly treatment sessions of group MCT for 10 weeks. The primary symptom outcome measure was severity of depression whilst secondary outcome measures included levels of anxiety, rumination and metacognitive beliefs. We also assessed recovery rates and changes in comorbid Axis I and Axis II diagnoses. RESULTS: Large clinically significant improvements across all measures were detected at post-treatment and these were maintained at follow-up. Based on objectively defined recovery criteria, all patients were classified as recovered at post-treatment and 91% at 6 months follow-up. The intervention was also associated with significant reductions in comorbid diagnoses. CONCLUSIONS: These preliminary data indicate that group MCT in the treatment of depression is effective, well accepted and it extends clinical application of MCT for depression to group formats as a potential cost-effective intervention. PMID- 25124120 TI - Methanol steam reforming promoted by molten salt-modified platinum on alumina catalysts. AB - We herein describe a straight forward procedure to increase the performance of platinum-on-alumina catalysts in methanol steam reforming by applying an alkali hydroxide coating according to the "solid catalyst with ionic liquid layer" (SCILL) approach. We demonstrate by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and temperature-programmed desorption (TPD) studies that potassium doping plays an important role in the catalyst activation. Moreover, the hygroscopic nature and the basicity of the salt modification contribute to the considerable enhancement in catalytic performance. During reaction, a partly liquid film of alkali hydroxides/carbonates forms on the catalyst/alumina surface, thus significantly enhancing the availability of water at the catalytically active sites. Too high catalyst pore fillings with salt introduce a considerable mass transfer barrier into the system as indicated by kinetic studies. Thus, the optimum interplay between beneficial catalyst modification and detrimental mass transfer effects had to be identified and was found on the applied platinum-on-alumina catalyst at KOH loadings around 7.5 mass%. PMID- 25124121 TI - Subtypes of non-suicidal self-injury based on childhood adversity. AB - The aim of this study was to examine the latent clusters in non-suicidal self injury (NSSI) based on childhood adversity. Data were derived from Waves I (2001 2002) and II (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of U.S. adults. Individuals engaging in NSSI (N = 672) comprised the analytic sample. Latent class statistical analysis was undertaken to elucidate the latent structure of NSSI based on child experiences of physical and sexual abuse, neglect, and family violence. Four-classes of respondents were identified vis-a-vis childhood adversities. A low abuse/neglect class (35.7% of respondents, 91.1% male) demonstrated less mental health and substance use comorbidity and antisocial behavior. A sexual abuse class (43.1% of respondents, 98.6% female) evinced somewhat lower levels of antisocial behavior than the other classes but similarly high levels of mental health disorder and a non-sexual abuse/neglect class (8.3% of respondents, 91.5% male) characterized by varied and intensive forms of antisocial and externalizing behaviors. Finally, a severe high abuse/neglect/family violence class (12.95% of respondents, 100% female) demonstrated high levels of clinical psychiatric and personality disorders. The current project is a nationally representative study of NSSI latent clusters and extends and validates the existence of NSSI subtypes revealed by prior research. PMID- 25124122 TI - [Medical consultation concerning the productive aged population and air pollution in Bogota: 2008 and 2010]. AB - OBJECTIVE: Exploring the relationship of current air pollution levels in Bogota for breathable particulate matter (<10 microns) PM10 and medical consultation during productive age (18 to 65 years old). METHODS: Data regarding Bogota's air quality monitoring network for 2008 to 2010 was reviewed, specifically PM10 levels and diagnosis arising from medical consultations in Bogota's public hospitals during this time. RESULTS: According to the air quality monitoring network's results there was an 8 MUg/m3 decrease in annual average PM10 from 2008 to 2010 (11.9 %) and, although consultations on grounds relating to air pollution increased by 58.7 % from 2008 to 2010, an overall 1.2 % decrease was observed when comparing this to the total of medical consultations each year. CONCLUSIONS: A significant percentage of medical attention provided in Bogota may be related to its air quality; the set of control policies developed in Bogota for some time now have led to a significant reduction in PM10 levels. PMID- 25124123 TI - [Air pollution and respiratory illness in children aged less than 5 years-old in Bogota, 2007]. AB - OBJECTIVES: Determining the relationship between indoor and outdoor air pollution caused by particulate matter PM10 and respiratory symptoms in children aged younger than 5 years-old in three locations in Bogota. METHODS: This was a cohort study, involving 315 children in kindergartens located in the area of greatest exposure to PM10, and 304 in kindergartens located in an area of less exposure. The cohort was followed-up for 19 weeks considering respiratory symptoms. Particulate matter was intramurally and extramurally measured in the kindergartens. Prevalence and association between variables were determined. RESULTS: There was a difference regarding average intramural PM between higher and lower exposure (85.6 ug/m3cf 61.8 g/m3; p<0.05); 74.3 % of the children had suffered wheezing during the last year, difference between greater and lesser exposure being 79.6 % cf 69.0 % (p<0.05). Wheezing and coughing were associated with greater exposure to PM10 (RR 1.39 and 1.30). Factors associated with respiratory symptoms concerned passive smoking, having a history of low birth weight, a history of wheezing, a child's kindergarten or home being within 100 meters of (industrial) chimneys, high traffic flow routes, roads in disrepair and bed-sharing. DISCUSSION: A child aged less than 5 years-old exposed to PM10 had a 1.7 times higher risk of truancy due to acute respiratory illness; a decrease in PM10 reduced such truancy by 41.1 %. PMID- 25124124 TI - [Constructing a tool for certifying handicap / disability in Colombia]. AB - OBJECTIVE: Describing how a tool was created/constructed for certifying Colombian people's disability status. METHOD: This was a descriptive study involving a five phase, multi-method design. It sought to identify needs, background, categories and procedures from differing view points, using participatory methodology, for identifying and certifying disabled people in Colombia. RESULTS: The study led to an international classification of functioning, disability and health (ICF)-based certification tool which can be used by a multi-professional team in healthcare institution settings to guarantee access to benefits approved by Colombian disability law. CONCLUSIONS: Certification (even when voluntary) can be the key to enjoying all the benefits designed for Colombian people suffering disability; such people are not the subjects of mercy and compassion anymore. Certification seeks to identify people suffering disabilities as holders of rights under Colombian law, as clear evidence of Colombian state commitment to ensuring an inclusive society. PMID- 25124125 TI - [Inequality regarding maternal mortality in Colombian departments in 2000-2001, 2005-2006 and 2008-2009]. AB - OBJECTIVE: Describing inequality regarding maternal mortality in Colombia for 2000-2001, 2005-2006 and 2008-2009. METHODS: This was an ecological study. The maternal mortality rate (MMR) was estimated, adjusted for maternal age, Colombian department and causes of maternal mortality. The main causes of mortality were described for 2000-2001, 2005-2006 and 2008-2009. The excess of risk of maternal death in Colombia was calculated regarding the best external referent using the attributable fraction (AF). The AF was correlated with the indicator of unsatisfied basic needs (UBN) by department. RESULTS: The highest MMR in Colombia was between 81 and 161 per 100,000 live births and the lowest between 3 and 5; the lowest MMR in the world was between 2 and 4 per 100,000 live births for the same periods. The main causes of maternal mortality in Colombia were hypertension during pregnancy, unclassified obstetric conditions and complications when giving birth. An excess of risk of maternal mortality in Colombia was found (on average 86 %) when compared to an external referent. A correlation was found between AF and UBN. CONCLUSIONS: Great inequality was found regarding maternal mortality in Colombia and when comparing Colombia to developed countries. Inequality regarding maternal mortality persists in spite of advances having been made regarding reform of the healthcare system, thereby suggesting that this has not been effective in reducing maternal mortality and its inequalities. PMID- 25124126 TI - [Socio-demographic and healthcare conditions regarding maternal self sufficiency/effectiveness concerning preventing diarrhea during childhood]. AB - OBJECTIVE: Investigating the correlation between socio-demographic conditions, health and maternal self-efficacy to prevent childhood diarrhoea. METHODS: This was a quantitative cross-sectional study which was conducted in Fortaleza, in north-eastern Brazil; it involved 448 mothers of children aged less than 5 years old. Data was collected through interviews held in the family healthcare centres using an in-house maternal self-efficacy for childhood diarrhoea prevention scale and a form for collecting information about the mothers' socio-demographic profile. RESULTS: The self-sufficiency/effectiveness in preventing diarrhoea during childhood interview data revealed a statistically significant association with maternal age (p=0.018), per capita income (p=0.023), type of housing (p=0.032), garbage disposal from the dwelling (p=0.000), origin of the water drunk by the children (p=0.002), type of sanitary installation (p=0.001) and its location (p=0.023), type of drainage (p=0.046) and the resources used by the mothers regarding their personal hygiene (p=0.002). CONCLUSIONS: Healthcare staff should advance strategies for improving self-sufficiency/effectiveness regarding maternal care for children, especially regarding preventative measures concerning diarrhoea during childhood. PMID- 25124127 TI - [IMCI and the maternal practice of African descendants' living on the Colombian Caribbean coast regarding the common cold and diarrhea]. AB - OBJECTIVE: Evaluating maternal practice regarding diarrhoea and the common cold. METHOD: This was a cross-sectional descriptive study which was conducted on the island of Baru, near Cartagena, Colombia. It involved 127 mothers of African descent and their 138 children aged less than 5 years of age; convenience sampling was used. The Integrated Management of Childhood Illness (IMCI) instrument was used for the survey during a one-day healthcare session. The prevalence of diarrhoea and the common cold during the 7 days immediately before the survey were estimated, as were maternal practice regarding these and the occurrence of other risks and protective factors; a history of breastfeeding, complementary feeding and vaccination was compiled. Descriptive statistics were used and the chi2 test was used for ascertaining the significance of the relationships between variables. RESULTS: Diarrhoea prevalence was 71.7 % (64-79 95 % CI), this being lower for girls aged 2 months to 5 years-old (p = 0,02) and common cold prevalence was 99.2 % (97-100 95 % CI), this being higher in girls aged older than 2 months (p=0.004). 86.9 % (81-92 95 % CI) of the mothers did not know how to identify warning signs for these diseases, 84.9 % (78-90 95 % CI) of the practices were inadequate and 73.3% of the mothers took their children to a doctor as their first line medical practice (p=0.05). CONCLUSIONS: Efforts must be increased regarding the implementation of the IMCI strategy in vulnerable communities, through effective channels of communication and innovative ways to reduce child morbidity and mortality indices, thereby promoting the island's social development. PMID- 25124129 TI - [An analysis of low birth weight in Colombia, 2005-2009]. AB - OBJECTIVE: Analysing Colombia's low birth weight pattern over a five-year period (2005 to 2009) and identifying the determinants and risk factors associated with such low birth weight rate. METHODS: This was a retrospective descriptive study which used the information contained in live birth certificates. Ratios were calculated for each selected variable and a multivariate logistic regression model was used for determining the associated predictors. RESULTS: The low birth weight rate was 8.6 % on average, this being higher in urban areas (8.9 %) and in the new born of mothers affiliated to the Colombian social security health insurance system's contributory regime (9.2 %). The low birth weight rate was higher in mothers lacking education (9.7 %) and those having a university or higher level of education (9.1 %). The predictors associated with the full-term newborn were caesarean delivery (OR 1.49), being female (OR 1.47), having attended less than four prenatal visits (OR 1.32), those being pregnant for the first time (OR 1.28) and being a single mother (OR 1.17). CONCLUSIONS: The low birth weight rate has increased each year and is linked to factors such as type of delivery, a child's gender, the number of prenatal visits, the number of previous live births, marital status, educational level and maternal age. These factors should form the target for Colombian public health policy and intervention. PMID- 25124128 TI - [Nutritional state associated with social determinants in Arhuaco children aged less than 5 years-old]. AB - OBJECTIVES: Misinformation concerning indigenous communities is an obstacle to ascertaining their healthcare status; however, the role of malnutrition concerning their morbidity and mortality is unquestionable. The aim of this study was to ascertain food security levels and identify social determinants and their association with the nutritional status of children aged less than five years old. METHODOLOGY: This was a cross-sectional, analytical study of an Arhuaco population which used non-probability sampling for convenience. Anthropometry included analyzing weight, length and head circumference based on WHO 2006 references for nutritional diagnosis. Social determinants were obtained using an instrument adapted from the Pan American Health Organization (PAHO). Relevant ethical considerations were taken into account. RESULTS: 169 children were evaluated and 132 surveys conducted. Growth delay regarding size was less frequent in children aged less than 6 months (p=0.03)and acute malnutrition was higher in those who went to see a traditional doctor first (p=0.01) and whose mothers had no formal schooling (p=0.05); the latter association was also found regarding obesity (p=0.00) and in those having risk factors concerning neurodevelopment too (p=0.00). Nutritional transition was higher in males (p=0.03), in children lacking complete vaccination (p=0.03) and in those whose mothers had 4 or fewer children (p=0.00). CONCLUSIONS: Strategies aimed at taking action regarding acute malnutrition and being overweight must be formulated, plans for monitoring growth in this population must be promoted and communication between traditional and Western medicine must be optimized, involving mothers as the main actors. PMID- 25124130 TI - Effect of biomass smoke on chronic obstructive pulmonary disease in rural localities of Colombia. AB - OBJECTIVES: The aim of this study was to assess the differences associated to the change of biofuel used to cook as a way to estimate the proportion of respiratory abnormalities of respiratory function associated to biomass exposure. METHODS: A cross-sectional study was designed to evaluate the respiratory function through spirometry in subjects cooking with biomass or natural gas. All patients were evaluated by a general physician and a pulmonologist. We compared the prevalence of spirometry abnormalities across those cooking with natural gas versus those cooking with biofuel. A multivariable logistic regression and multiple linear regression were used to adjust differences by potential confounding factors. RESULTS: 203 subjects were studied. There was a significant increase in the prevalence of severe obstructive pattern (OR 5.50; 95 % CI 1.17-25.79) in subjects who cook with biomass compared with natural gas users. Values of forced expired volume in one second (FEV1) and forced vital capacity (FVC) were statistically lower among those cooking with biomass. The prevalence of respiratory morbidity and symptoms were not statistically significant between both groups. CONCLUSIONS: These findings suggest that replacing biomass fuel by natural gas may be an important public health intervention in Colombia, because it can reduce the prevalence of abnormal patterns of pulmonary function. PMID- 25124131 TI - [Muscular strength training does not increase human adults' arterial stiffness or improve body toning]. AB - OBJECT: Determining the influence of three weekly strength training (ST) sessions, over a ten-week period, on arterial stiffness (AS) and taking the associated anthropometric measurements. METHODS: This was a before-and-after intervention trial, involving a sample of 17 individuals. Participants were adults from both genders aged 18 and 40 years-old who had been sedentary for at least three months previously. Anthropometric measurements were taken, together with pulse wave velocity (PWV) before and immediately after the experimental sessions. RESULTS: Independent variables (age and gender) were considered for determining their influence on final PWV and anthropometric measurements. Comparing initial PWV (mean=9.00) with final PWV (mean=9.00) for subjects involved in the proposed ST revealed no significant difference between them (p=0.469). Regarding anthropometric measurement, individuals' body fat (p<0.001) and body fat mass percentages (p<0.001) became significantly reduced, accompanied by an increase in lean mass (p<0.001). However, no changes were recorded regarding waist-to-hip ratio (WHR) (p= 0.777), body mass (p=0.226) or body mass index (BMI) (p =0.212). CONCLUSION: This study's findings suggested that the proposed ST did not increase AS. Devotees of such type of training may therefore safely enjoy all its benefits without risk to the cardiovascular system. Further controlled and randomized research is needed to confirm these results. PMID- 25124132 TI - [An occupational assessment of disabled people in Colombia: an exploratory analysis of ongoing practice]. AB - OBJECTIVE: This paper analyses a study of the current state of occupational assessment of disabled people; it took place in 14 public and private institutions involved in promoting the inclusion of this population in the workforce. The study was aimed at providing definitions, demonstrating the pertinent processes, instruments, professionals, stages of the process and support involved in helping disabled people to become included in the workforce. METHODOLOGY: The study involved a group of experts adopting a methodology which designed, implemented and analysed a data collection instrument seeking qualitative and quantitative data concerning target populations, assessment purposes, the instruments used, timing and other relevant factors for programmes aimed at disabled people becoming included in the workforce. The 14 Colombian institutions having most experience regarding this topic participated in the study (the oldest having 40 years' experience and the most recent 8 years in this field). RESULTS: The results indicated widespread heterogeneity regarding the occupational assessment components explored. It was found that the objectives proposed for each process differed, depending on each institution's philosophy and structure, the model's characteristics and those of the intraprofessional teams. They also highlighted the broad range of instruments and timing (i.e. 1 to 180 days) of sub-processes used as tools for occupational assessment (of the disabled). CONCLUSIONS: These findings constitute a foundation justifying the compilation of a Manual for the Occupational Assessment of Disabled People in Colombia, recognising accumulated cognitive, social and professional capital (i.e. established tradition in this field). PMID- 25124134 TI - [Modelling respiratory syncytial virus (RSV) transmission children aged less than five years-old]. AB - OBJECTIVES: Studying respiratory syncytial virus (RSV) transmission dynamics in a population of children aged less than 5 years-old using deterministic models. METHOD: A deterministic susceptible-infected-removed(SIR) mathematical model with seasonal forcing was used for the simulation. RESULTS: A mathematical epidemiological model (SIRS) with seasonal forcing was proposed which explained RSV dynamics between 2005 and 2010 in a population of children aged less than five years-old in Bogota. CONCLUSIONS: The mathematical model (SIRS) with seasonal forcing explained the cyclical pattern of cases of children aged less than five years old infected with RSV in Bogota, Colombia during the target period. PMID- 25124133 TI - [Knowledge about dengue and cardio-cerebrovascular disease in a town in Colombia]. AB - OBJECTIVE: This study aimed at describing a low-income population's knowledge and perception concerning dengue and cardio-cerebrovascular disease in a town in Colombia. METHOD: The study involved qualitative research; data from 16 semi structured individual and 3 focus groups was collected through questionnaires addressing 3 low-income sectors and then interpreted. Deductive categorisation of data was based on the questions and inductive analysis to establish such population's knowledge for studying their perceptions regarding dengue and cardio cerebrovascular disease. RESULTS: It was evident that the target population knew about the agents, the forms of acquiring such diseases, the risk factors and action to be taken for preventing and controlling both diseases; however, such knowledge did not represent (i.e. had not led to) changes in their daily practice or lifestyles. CONCLUSIONS: Local health centre actions needs to be supported by theory or models and must go beyond single interventions based essentially on the transmission of information. PMID- 25124135 TI - Pain and inflammation in hidradenitis suppurativa correspond to morphological changes identified by high-frequency ultrasound. AB - BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin disease with a chronic intermittent course. The current classification systems used to categorize disease severity provide limited insight into the degree of inflammation and pain, which are key symptoms of the disease. OBJECTIVE: We sought to investigate the correlation and validity of simple patient- and investigator-assessed items related to inflammation with morphological changes identified by high-frequency ultrasound in HS. METHODS: Twenty patients with the clinical diagnosis of HS were enrolled in this study. All patients underwent clinical examinations during which one representative inflammatory nodule was selected in each patient based on the anamnestic information, patient experience and clinical presentation. Tenderness and flare activity of the representative nodule were graded by the patients and erythema by the investigator. Subsequently, all patients underwent high-resolution ultrasound scanning of their representative nodule. RESULTS: We found significant associations between the size of the representative nodule (the diameter in the transverse plane) and patient assessments of flare activity and tenderness. Moreover, we found a marked association between the size of the nodules and investigator assessment of erythema. CONCLUSION: Patient assessments of flare activity and pain, and investigator assessment of erythema are strongly associated with morphological changes identified using ultrasound, suggesting that these patient- and investigator-assessed items might be strong indicators of the degree of present inflammation in HS. PMID- 25124136 TI - Comparison of the microbiological quality of environmentally friendly and conventionally grown vegetables sold at retail markets in Korea. AB - Fresh produce is usually eaten raw without cooking or heating, which may increase the probability of foodborne infection. The microbiological quality of 11 types of fresh, raw vegetables (romaine lettuce, sesame leaves, crown daisy, garlic chives, iceberg lettuce, cabbage, broccoli, leek, chili pepper, capsicum, and zucchini) purchased at retail markets in Iksan, Korea as affected by cultivation method (environmentally friendly vegetables [organic, pesticide-free, and low pesticide vegetables] and conventionally grown vegetables) and harvest season was determined. Escherichia coli O157:H7 and Salmonella were not detected in all samples of vegetables tested. Aerobic mesophiles (>6 log cfu/g) were detected in environmentally friendly romaine lettuce and crown daisy and environmentally friendly and conventionally grown garlic chives, which also contained coliforms (>3 log cfu/g). Sesame leaf and crown daisy (regardless of cultivation method), as well as conventionally grown romaine lettuce and leek, contained >1 log cfu/g of E. coli. The overall microbiological quality of environmentally friendly and conventionally grown vegetables was not significantly different (P > 0.05). However, there were seasonal effects on populations of coliforms and generic E. coli on vegetables. The greatest numbers of microorganisms were isolated from environmentally friendly or conventionally grown vegetables purchased in winter. The vegetables, regardless of cultivation method or season, should be subjected to appropriate antimicrobial treatment to enhance their microbial safety. PMID- 25124137 TI - Optimizing oxygen delivery in the critically ill: the utility of lactate and central venous oxygen saturation (ScvO2) as a roadmap of resuscitation in shock. AB - BACKGROUND: Resuscitation of any critically ill patient is aimed at restoration of oxygen delivery to maintain aerobic metabolism. Thus, "endpoints" of resuscitation have been sought after as a measure of evaluating the adequacy of resuscitation. This review article describes the most commonly used endpoints, central venous oxygen saturation (ScvO2) and lactate, and provides a clinically useful paradigm for utilizing these endpoints during resuscitation of critically ill patients in the emergency department (ED). OBJECTIVE: This review article will summarize the pathophysiology of cellular shock, describe the available research regarding lactate and ScvO2, and provide an approach to utilizing these endpoints during resuscitation in the ED. DISCUSSION: ScvO2 and lactate each have been shown to be useful for the assessment of shock, yet each has inherent limitations. When used together, ScvO2 and lactate provide the emergency physician with a glimpse of the underlying pathophysiologic state, allowing targeted therapy to restore oxygen delivery. CONCLUSION: ScvO2 and lactate are useful endpoints of resuscitation, and when used together, provide a metabolic framework for guiding targeted therapy for critically ill patients in the ED with shock. PMID- 25124138 TI - Entrustable professional activities: making sense of the emergency medicine milestones. AB - BACKGROUND: The Next Accreditation System (NAS) is being implemented by the Accreditation Council for Graduate Medical Education with seven specialties, including Emergency Medicine (EM), which began in July 2013. The NAS represents a more structured method of accreditation, with dependence on outcomes and less emphasis on educational process. A key component of the NAS is the individual resident semiannual reporting of the Milestone proficiency levels for all sub competencies, which are more specific areas of domain for the general competencies. All specialties are struggling to some extent with developing assessment mechanisms for the Milestones. At the heart of this struggle is the conceptualization of the Milestones themselves-descriptors of the individual. In practice, faculty assess clinical care provided to the patient by the resident. This creates difficulty for faculty to assign a resident to a specific sub competency proficiency level when their focus has been on assessment of clinical care. OBJECTIVES: The objectives of this article include the discussion of whether Entrustable Professional Activities (EPAs) could be defined and linked to milestones in a way that, once implemented, could inform Clinical Competency Committees of the Milestone proficiency reporting. DISCUSSION: EPAs are units of professional work, or clinical care that may help translate aspects of clinical care into Milestone proficiencies. This article explores EPAs in depth, and discusses how EPAs may be used within EM as one method of assigning proficiency levels to residents. CONCLUSIONS: EPAs may be a useful tool to inform Milestone proficiency placement of residents. Because EPAs are based on clinical descriptions rather than individual physician descriptions, there may be less faculty development needed for Milestone sub-competency assessment. PMID- 25124139 TI - [Sedation in endoscopic procedures performed by intensivists]. PMID- 25124140 TI - HIV testing preferences in Tanzania: a qualitative exploration of the importance of confidentiality, accessibility, and quality of service. AB - BACKGROUND: HIV counseling and testing (HCT), an effective preventive strategy and an entry point for care, remains under-utilized in Tanzania. Limited uptake of HCT, despite the widespread availability of varied testing options, suggests that existing options may not align well with population preferences for testing. METHODS: Between October and December 2011, we conducted an exploratory study in the Kilimanjaro Region to develop a conceptual framework for understanding which characteristics of HIV testing are associated with preferences for testing. Forty individuals (55% women, 53% never having tested) participated in in-depth interviews and focus groups to identify factors that influence whether and where people test for HIV. RESULTS: A variety of discrete characteristics of testing venues, test providers, and testing procedures (e.g. distance to testing, counselor experience, type of HIV test, and availability of antiretroviral therapy) mapped conceptually to three domains: confidentiality of testing and test results, quality of HCT, and accessibility and availability of ancillary services. We noted heterogeneous preferences and demonstrate that while some test characteristics overlap and reinforce across multiple domains, others demand clients to make trade-offs between domains. CONCLUSION: Testing decisions appear to be influenced by an array of often inter-linked factors across multiple domains, including quality, confidentiality, and accessibility; perceptions of these factors varied greatly across participants and across available testing options. HCT interventions that jointly target barriers spanning the three domains have the potential to increase uptake of HIV testing and deserve further exploration. PMID- 25124142 TI - Uranium incorporation into aluminum-substituted ferrihydrite during iron(ii) induced transformation. AB - Uranium retention processes (adsorption, precipitation, and incorporation into host minerals) exert strong controls on U mobility in the environment, and understanding U retention is therefore crucial for predicting the migration of U within surface and groundwater. Uranium can be incorporated into Fe (hydr)oxides during Fe(ii)-induced transformation of ferrihydrite to goethite. However, ferrihydrite seldom exists as a pure phase within soils or sediments, and structural impurities such as Al alter its reactivity. The presence of Al in ferrihydrite, for example, decreases the rate of transformation to goethite, and thus may impact the retention pathway, or extent of retention, of U. Here, we investigate the extent and pathways of U(vi) retention on Al-ferrihydrite during Fe(ii)-induced transformation. Ferrihydrite containing 0%, 1%, 5%, 10%, and 20% Al was reacted with 10 MUM U and 300 MUM Fe(ii) in the presence of 0 mM and 4 mM Ca(2+) and 3.8 mM carbonate at pH 7.0. Solid reaction products were characterized using U L3-edge EXAFS spectroscopy to differentiate between adsorbed U and U incorporated into the goethite lattice. Uranium incorporation into Al ferrihydrite declined from ~70% of solid-phase U at 0% and 1% Al to ~30% of solid phase U at 20% Al content. The decrease in U incorporation with increasing Al concentration was due to two main factors: (1) decreased transformation of ferrihydrite to goethite; and, (2) a decrease of the goethite lattice with increasing Al, making the lattice less compatible with large U atoms. However, uranium incorporation can occur even with an Al-substituted ferrihydrite precursor in the presence or absence of Ca(2+). The process of U incorporation into Al-goethite may therefore be a potential long-term sink of U in subsurface environments where Al-substituted iron oxides are common, albeit at lower levels of incorporation with increasing Al content. PMID- 25124141 TI - Follow-up on pediatric patients with bronchiolitis obliterans treated with corticosteroid pulse therapy. AB - BACKGROUND: Bronchiolitis obliterans (BO) is a rare but severe disease in children. Currently, there is no consensus on the treatment for BO with respect to the systemic use of corticosteroids. Here we report on the follow-up of children with a diagnosis of BO who were treated with corticosteroid pulse therapy. METHODS: Forty patients fulfilling the BO diagnosis criteria were treated with methylprednisolone pulse therapy in monthly cycles until clinical improvement. After the pulse therapy began, we analyzed the clinical and laboratory data at intervals. Statistical analyses were performed using non parametric tests to compare repeated measures (Friedman, Wilcoxon) or paired nominal data (McNemar) (alpha = 5%). RESULTS: The frequency of wheezing exacerbations and hospitalizations was reduced (p = 0.0042 and p < 0.0001, respectively) and oxygen saturation improved (p = 0.0002) in the pulse therapy treated patients. Prolonged oral corticosteroid therapy was discontinued in 83% of these patients. The mean Z-score length for age improved from -1.08 to -0.63, and the mean Z-score weight for age improved from -0.91 to -0.59. The adverse effects during the infusion were temporary and none were serious. CONCLUSIONS: Our data suggest that pulse corticotherapy could be a safe alternative to prolonged systemic oral corticotherapy in children with BO, thus minimizing the adverse effects of the oral therapy. New prospective controlled studies are required to confirm this proposition. PMID- 25124143 TI - The macropod type 2 interferon gene shares important regulatory and functionally relevant regions with eutherian IFN-gamma. AB - Interferon-gamma (IFN-gamma) is an important immune regulatory molecule that plays a significant role in internal and external modulation of the mammalian immune response to intracellular pathogens. Herein, we report the 492 nt expressed sequence for the coding domain of IFN-gamma from the immune tissues of two Australian macropod marsupial species: the tammar wallaby (Macropus eugenii) and the vulnerable rufous hare-wallaby (Lagorchestes hirsutus). Both 5' and 3' untranslated regions and the coding domain of M. eugenii IFN-gamma revealed the presence of motifs responsible for transcriptional regulation, mRNA regulation, post-translational modifications, and receptor binding in other mammals. Since diagnostic kits for mycobacterial disease commonly rely on the assessment of interferon levels, we can now use this information to develop reagents that can be applied in clinical and laboratory settings to further our understanding of marsupial responses to disease. PMID- 25124144 TI - ISA virus regulates the generation of reactive oxygen species and p47phox expression in a p38 MAPK-dependent manner in Salmo salar. AB - Several viruses, including Orthomyxovirus, utilize cellular reactive oxygen species (ROS) for viral genomic replication and survival within host cells. However, the role of ROS in early events of viral entry and signal induction has not been elucidated. Here, we show that ISA virus (ISAV) induces ROS production very early during infection of CHSE-214 and SHK-1Ycells, and that production is sustained over the observed 24h post-infection. The mitogen-activated protein kinase (MAPK) family is responsible for important signaling pathways. In this study, we report that ISAV activates ERK and p38 in Salmo salar. In salmonid macrophages, while ERK was required for SOD, GLURED, p47phox expression, p38 regulated the ROS production by the NADPH oxidase complex activation. These results, together with the presence of several consensus target motifs for p38 MAPK in the promoter of the S. salar p47phox gene, suggest that p38 MAPK regulates p47phox gene expression in fish through the activation of this key transcription factor. PMID- 25124145 TI - Complement activation-related pseudoallergy: a stress reaction in blood triggered by nanomedicines and biologicals. AB - Intravenous injection of a variety of nanotechnology enhanced (liposomal, micellar, polymer-conjugated) and protein-based (antibodies, enzymes) drugs can lead to hypersensitivity reactions (HSRs), also known as infusion, or anaphylactoid reactions. The molecular mechanism of mild to severe allergy symptoms may differ from case to case and is mostly not known, however, in many cases a major cause, or contributing factor is activation of the complement (C) system. The clinical relevance of C activation-related HSRs, a non-IgE-mediated pseudoallergy (CARPA), lies in its unpredictability and occasional lethal outcome. Accordingly, there is an unmet medical need to develop laboratory assays and animal models that quantitate CARPA. This review provides basic information on CARPA; a short history, issues of nomenclature, incidence, classification of reactogenic drugs and symptoms, and the mechanisms of C activation via different pathways. It is pointed out that anaphylatoxin-induced mast cell release may not entirely explain the severe reactions; a "second hit" on allergy mediating cells may also contribute. In addressing the increasing requirements for CARPA testing, the review evaluates the available assays and animal models, and proposes a possible algorithm for the screening of reactogenic drugs and hypersensitive patients. Finally, an analogy is proposed between CARPA and the classic stress reaction, suggesting that CARPA represents a "blood stress" reaction, a systemic fight of the body against harmful biological and chemical agents via the anaphylatoxin/mast-cell/circulatory system axis, in analogy to the body's fight of physical and emotional stress via the hypothalamo/pituitary/adrenal axis. In both cases the response to a broad variety of noxious effects are funneled into a uniform pattern of physiological changes. PMID- 25124146 TI - Global biogeography of Alnus-associated Frankia actinobacteria. AB - Macroecological patterns of microbes have received relatively little attention until recently. This study aimed to disentangle the determinants of the global biogeographic community of Alnus-associated actinobacteria belonging to the Frankia alni complex. By determining a global sequence similarity threshold for the nitrogenase reductase (nifH) gene, we separated Frankia into operational taxonomic units (OTUs) and tested the relative effects of Alnus phylogeny, geographic relatedness, and climatic and edaphic variables on community composition at the global scale. Based on the optimal nifH gene sequence similarity threshold of 99.3%, we distinguished 43 Frankia OTUs from root systems of 22 Alnus species on four continents. Host phylogeny was the main determinant of Frankia OTU-based community composition, but there was no effect on the phylogenetic structure of Frankia. Biogeographic analyses revealed the strongest cross-continental links over the Beringian land bridge. Despite the facultative symbiotic nature of Frankia, phylogenetic relations among Alnus species play a prominent role in structuring root-associated Frankia communities and their biogeographic patterns. Our results suggest that Alnus species exert strong phylogenetically determined selection pressure on compatible Actinobacteria. PMID- 25124147 TI - Congenital abnormalities of the vertebral column in ferrets. AB - Vertebral column pathologies requiring surgical intervention have been described in pet ferrets, however little information is available on the normal vertebral formula and congenital variants in this species. The purpose of this retrospective study was to describe vertebral formulas and prevalence of congenital vertebral anomalies in a sample of pet ferrets. Radiographs of 172 pet ferrets (96 males and 76 females) were included in this retrospective study. In 143 ferrets (83.14%), five different formulas of the vertebral column were recorded with normal morphology of vertebrae (rib attachment included) but with a variable number of thoracic (Th), lumbar (L), and sacral (S) vertebrae. The number of cervical (C) vertebrae was constant in all examined animals. Observed vertebral formulas were C7/Th14/L6/S3 (51.74%), C7/Th14/L6/S4 (22.10%), C7/Th14/L7/S3 (6.98%), C7/Th15/L6/S3 (1.74%), and C7/Th15/L6/S4 (0.58%). Formula C7/Th14/L6/S4 was significantly more common in males than in females (P < 0.05). Congenital spinal abnormalities were found in 29 ferrets (16.86%), mostly localized in the thoracolumbar and lumbosacral regions. The cervical region was affected in only one case. Transitional vertebrae represented the most common congenital abnormalities (26 ferrets) in the thoracolumbar (13 ferrets) and lumbosacral regions (10 ferrets) or simultaneously in both regions (three ferrets). Other vertebral anomalies included block (two ferrets) and wedge vertebra (one ferret). Spina bifida was not detected. Findings from the current study indicated that vertebral formulas may vary in ferrets and congenital abnormalities are common. This should be taken into consideration for surgical planning. PMID- 25124149 TI - Expression of microRNA miR-126 and miR-200c is associated with prognosis in patients with non-small cell lung cancer. AB - MicroRNAs (miRNAs) are short non-coding RNAs that exert a critical influence on tumorigenesis through post-transcriptional modification and are considered to be potential biomarkers for the diagnosis or prognosis of various cancers. Although several miRNAs have been proposed as relevant biomarkers for non-small cell lung cancer (NSCLC), detailed working mechanisms and validated prognostic significance of these miRNAs remain controversial. In this study, we evaluated expression levels of miRNA-126 (miR-126) and miR-200c in 72 NSCLCs and 30 benign lung tissues by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and analyzed the correlation of miRNA expression with a variety of clinicopathological factors and patient survival. Compared with the benign control group, miR-126 expression was significantly downregulated in NSCLCs (p < 0.001), while miR-200c expression was significantly upregulated in NSCLCs (p < 0.001). The expression of miR-126 was significantly higher in NSCLCs with a tumor size of <=3 cm than in those with a tumor size of >3 cm (p = 0.026). There were no other significant associations between miRNA expression and clinicopathological features. In univariate survival analysis for all NSCLC patients, high miR-200c expression (p = 0.037), large tumor size (p = 0.026), and lymphovascular invasion (p = 0.012) were significantly correlated with worse overall survival. High miR-126 expression was significantly associated with favorable prognosis only in patients with adenocarcinoma (p = 0.033). In multivariate analysis, miR-200c and tumor size remained as independent prognostic factors. Our results suggest that miR-126 might play tumor-suppressive and miR 200c an oncogenic role, and these miR's are potential prognostic biomarkers for NSCLC. PMID- 25124148 TI - Pallidal gap junctions-triggers of synchrony in Parkinson's disease? AB - Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin 36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia. PMID- 25124150 TI - High users of emergency departments in Quebec among patients with both schizophrenia and a substance use disorder. AB - OBJECTIVE: The study assessed factors associated over time with high use of emergency departments by patients in Quebec who had schizophrenia and a co occurring substance use disorder. METHODS: The cohort study included 2,921 patients who received a diagnosis of schizophrenia in 2006 and had at least one emergency department visit during fiscal year 2006-2007. Generalized estimating equations were used to estimate predictors of high use of emergency departments over time. RESULTS: After adjustment for all covariates, predictors of high use over time were as follows: living in either a university medical region (OR=2.10) or a peripheral medical region (OR=2.10), frequent hospitalization (OR=1.16), and greater number of psychiatric (OR=1.64) or physical comorbidities (OR=1.23). CONCLUSIONS: Because high use of emergency departments is a strong indicator of poor care continuity, identified associated factors could help develop and offer new programs to be deployed in the community to better support these patients with greater needs. PMID- 25124151 TI - Cochlear length determination using Cone Beam Computed Tomography in a clinical setting. AB - Indications for cochlear implants are determined by audiological and medical considerations. Clinical imaging is therefore an integral element for anatomical evaluation in terms of medical considerations. Several authors have discussed the variability of cochlear shape, especially cochlear length. Cochlear length is, however, an increasingly recognized parameter in terms of preoperative evaluation. This study introduces a methodology to determine individual cochlear length in clinical setting by using Cone Beam Computed Tomography. Cochlear length determination was performed retrospectively with an OsiriX curved 3D Multiplanar Reconstruction tool on subjects who underwent temporal bone imaging from January 2011 to February 2013. Cochlear length was defined as the spiral route from the center-distal point of the bony round window along the lateral wall towards the helicotrema, which is the endpoint of the measurement. Cochlear length was measured in 436 temporal bones (218 left ears, 218 right ears, 218 subjects). The mean cochlear length was 37.6 mm (SD: +/- 1.93 mm), median was 37.6 mm, range 32-43.5 mm. The cochlear length had a normal distribution. A significant difference was found between cochlear length by gender (p < .0001), but not between the left and right cochlea (p = .301) or according to age. Consideration of the cochlear length in clinical data may be an insufficiently represented parameter in cochlear implant treatment. Literature shows the impact of electrode insertion depth on residual hearing preservation and speech performance. Individual evaluation of the cochlear implant electrode choice may be the next step in personalized cochlear implant treatment as a valuable addition to existing audiological and surgical evaluation. The cochlear length determination methodology presented herein is a reproducible and clinically available parameter. Indeed, revealing a significant cochlear length span width, especially according to gender differences, may be assumed as hardly ignorable. PMID- 25124152 TI - Abnormal intelligibility of speech in competing speech and in noise in a frequency region where audiometric thresholds are near-normal for hearing impaired listeners. AB - The ability to identify syllables in the presence of speech-shaped noise and a single-talker background was measured for 18 normal-hearing (NH) listeners, and for eight hearing-impaired (HI) listeners with near-normal audiometric thresholds for frequencies up to 1.5 kHz and a moderate to severe hearing loss above 2 kHz. The stimulus components were restricted to the low-frequency (<=1.5 kHz) region, where audiometric thresholds were classified clinically as normal or near normal for all listeners. Syllable identification in a speech background was measured as a function of the fundamental-frequency (F0) difference between competing voices (ranging from 1 semitone to ~1 octave). HI listeners had poorer syllable intelligibility than NH listeners in all conditions. Intelligibility decreased by about the same amount for both groups when the F0 difference between competing voices was reduced. The results suggest that the ability to identify speech against noise or an interfering talker was disrupted in frequency regions of near normal hearing for HI listeners, but that the ability to benefit from the tested F0 differences was not disrupted. This deficit was not predicted by the elevated absolute thresholds for speech in speech, but it was for speech in noise. It may result from supra-threshold auditory deficits associated with aging. PMID- 25124153 TI - Differential modulation of auditory responses to attended and unattended speech in different listening conditions. AB - This study investigates how top-down attention modulates neural tracking of the speech envelope in different listening conditions. In the quiet conditions, a single speech stream was presented and the subjects paid attention to the speech stream (active listening) or watched a silent movie instead (passive listening). In the competing speaker (CS) conditions, two speakers of opposite genders were presented diotically. Ongoing electroencephalographic (EEG) responses were measured in each condition and cross-correlated with the speech envelope of each speaker at different time lags. In quiet, active and passive listening resulted in similar neural responses to the speech envelope. In the CS conditions, however, the shape of the cross-correlation function was remarkably different between the attended and unattended speech. The cross-correlation with the attended speech showed stronger N1 and P2 responses but a weaker P1 response compared to the cross-correlation with the unattended speech. Furthermore, the N1 response to the attended speech in the CS condition was enhanced and delayed compared with the active listening condition in quiet, while the P2 response to the unattended speaker in the CS condition was attenuated compared with the passive listening in quiet. Taken together, these results demonstrate that top down attention differentially modulates envelope-tracking neural activity at different time lags and suggest that top-down attention can both enhance the neural responses to the attended sound stream and suppress the responses to the unattended sound stream. PMID- 25124154 TI - Inner ear stem cells derived feeder layer promote directional differentiation of amniotic fluid stem cells into functional neurons. AB - Intact spiral ganglion neurons are required for cochlear implantation or conventional hearing amplification as an intervention for sensorineural hearing loss. Treatment strategies to replace the loss of spiral ganglion neurons are needed. Recent reports have suggested that amniotic fluid-derived stem cells are capable of differentiating into neuron-like cells in response to cytokines and are not tumorigenic. Amniotic fluid stem cells represent a potential resource for cellular therapy of neural deafness due to spiral ganglion pathology. However, the directional differentiation of amniotic fluid stem cells is undetermined in the absence of cytokines and the consequence of inner ear supporting cells from the mouse cochlea organ of Corti on the differentiation of amniotic fluid stem cells remains to be defined. In an effort to circumvent these limitations, we investigated the effect of inner ear stem cells derived feeder layer on amniotic fluid stem cells differentiation in vitro. An inner ear stem cells derived feeder layer direct contact system was established to induce differentiation of amniotic fluid stem cells. Our results showed that inner ear stem cells derived feeder layer successfully promoted directional differentiation of amniotic fluid stem cells into neurons with characteristics of functionality. Furthermore, we showed that Wnt signaling may play an essential role in triggering neurogenesis. These findings indicate the potential use of inner ear stem cells derived feeder layer as a nerve-regenerative scaffold. A reliable and effective amniotic fluid stem cell differentiation support structure provided by inner ear stem cells derived feeder layer should contribute to efforts to translate cell-based strategies to the clinic. PMID- 25124155 TI - NIR spectroscopic method for the in-line moisture assessment during drying in a six-segmented fluid bed dryer of a continuous tablet production line: Validation of quantifying abilities and uncertainty assessment. AB - This study focuses on the thorough validation of an in-line NIR based moisture quantification method in the six-segmented fluid bed dryer of a continuous from powder-to-tablet manufacturing line (ConsiGmaTM 25, GEA Pharma Systems nv, Wommelgem, Belgium). The moisture assessment ability of an FT-NIR spectrometer (MatrixTM-F Duplex, Bruker Optics Ltd, UK) equipped with a fiber-optic Lighthouse ProbeTM (LHP, GEA Pharma Systems nv, Wommelgem, Belgium) was investigated. Although NIR spectroscopy is a widely used technique for in-process moisture determination, a minority of NIR spectroscopy methods is thoroughly validated. A moisture quantification PLS model was developed. Twenty calibration experiments were conducted, during which spectra were collected at-line and then regressed versus the corresponding residual moisture values obtained via Karl Fischer measurements. The developed NIR moisture quantification model was then validated by calculating the accuracy profiles on the basis of the analysis results of independent in-line validation experiments. Furthermore, as the aim of the NIR method is to replace the destructive, time-consuming Karl Fischer titration, it was statistically demonstrated that the new NIR method performs at least as good as the Karl Fischer reference method. PMID- 25124156 TI - Flow cytometric enumeration of bacteria using TO-PRO(r)-3 iodide as a single stain viability dye. AB - Quantification of bacteria using conventional viable plate counting (VPC) is labor-intensive and time-consuming. Flow cytometry (FCM) can be proposed as a faster alternative. This study aimed to develop a flow cytometric, single-stain approach using TO-PRO(r)-3 iodide (TP3) for the quantification of Staphylococcus aureus, Escherichia coli, and Bacillus subtilis cells. Live or dead bacterial suspensions were stained with TP3 and analyzed using a FACSCalibur flow cytometer. After optimization of staining parameters and instrument settings, an excellent separation of viable and dead cells was achieved for all species. The quantitative performance of the technique was assessed by analyzing serial dilutions of bacterial suspensions using FCM and VPC. A highly linear correlation (r2 > 0.99) was observed between the colony forming units (CFU)/mL as determined by FCM and by VPC over a concentration range of about 104 to 108 CFU/mL. As such, FCM quantification of viable bacteria using TP3 can be considered as an accurate and reliable alternative for VPC. The monostain procedure is easy to apply and cost-effective, and it allows bacterial enumeration in a broad variety of samples. PMID- 25124157 TI - Laboratory automation in a functional programming language. AB - After some years of use in academic and research settings, functional languages are starting to enter the mainstream as an alternative to more conventional programming languages. This article explores one way to use Haskell, a functional programming language, in the development of control programs for laboratory automation systems. We give code for an example system, discuss some programming concepts that we need for this example, and demonstrate how the use of functional programming allows us to express and verify properties of the resulting code. PMID- 25124158 TI - Reactions of rac-(ebthi)M(eta(2) -Me3 SiC2 SiMe3 ) (M=Ti, Zr) with aryl nitriles. AB - The reactions of the Group 4 metallocene alkyne complexes rac-(ebthi)M(eta(2) Me3 SiC2 SiMe3 ) (1 a: M=Ti, 1 b: M=Zr; rac-(ebthi)=rac-1,2-ethylene-1,1' bis(eta(5) -tetrahydroindenyl)) with Ph?C?N were investigated. For 1 a, an unusual nitrile-nitrile coupling to 1-titana-2,5-diazacyclopenta-2,4-diene (2) at ambient temperature was observed. At higher temperature, the C?C coupling of two nitriles resulted in the formation of a dinuclear complex with a four-membered diimine bridge (3). The reaction of 1 b with Ph?C?N afforded dinuclear compound 4 and 2,4,6-triphenyltriazine. Additionally, the reactivity of 1 b towards other nitriles was investigated. PMID- 25124159 TI - A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. AB - BACKGROUND: Almost one-third of congenital cataracts are primarily autosomal dominant disorders, which are also called autosomal dominant congenital cataract, resulting in blindness and clouding of the lens. The purpose of this study was to identify the disease-causing mutation in a Chinese family affected by bilateral, autosomal dominant congenital cataract. METHODS: The detection of candidate gene mutation and the linkage analysis of microsatellite markers were performed for the known candidate genes. Molecular mapping and cloning of candidate genes were used in all affected family members to screen for potential genetic mutations and the mutation was confirmed by single enzyme digestion. RESULTS: The proband was diagnosed with isolated, congenital cataract without the typical clinical manifestations of cataract, which include diabetes, porencephaly, sporadic intracerebral hemorrhage, and glomerulopathy. A novel mutation, c.2345 G > C (Gly782Ala), in exon 31 of the collagen type IV alphalpha1 (COL4A1) gene, which encodes the collagen alpha-1(IV) chain, was found to be associated with autosomal dominant congenital cataract in a Chinese family. This mutation was not found in unaffected family members or in 200 unrelated controls. Sequence analysis confirmed that the Gly782 amino acid residue is highly conserved. CONCLUSIONS: The novel mutation (c.2345 G > C) of the COL4A1 gene is the first report of a non syndromic, autosomal dominant congenital cataract, thereby highlighting the important role of type IV collagen in the physiological and optical properties of the lens. PMID- 25124160 TI - Real-time near-infrared fluorescence guided surgery in gynecologic oncology: a review of the current state of the art. AB - Near-infrared (NIR) fluorescence imaging has emerged as a promising complimentary technique for intraoperative visualization of tumor tissue, lymph nodes and vital structures. In this review, the current applications and future opportunities of NIR fluorescence imaging in gynecologic oncology are summarized. Several studies indicate that intraoperative sentinel lymph node identification in vulvar cancer using NIR fluorescence imaging outperforms blue dye staining and provides real time intraoperative imaging of sentinel lymph nodes. NIR fluorescence imaging can penetrate through several millimeters of tissue, revealing structures just below the tissue surface. Hereby, iatrogenic damage to vital structures, such as the ureter or nerves may be avoided by identification using NIR fluorescence imaging. Tumor-targeted probes are currently being developed and have the potential to improve surgical outcomes of cytoreductive and staging procedures, in particular in ovarian cancer. Research in the near future will be necessary to determine whether this technology has additional value in order to facilitate the surgical procedure, reduce morbidity and improve disease-free and overall survival. PMID- 25124162 TI - SGO guidance document for clinical trial designs in ovarian cancer: a changing paradigm. AB - OBJECTIVE: To explore and facilitate the multifaceted process of drug development and regulatory approval in ovarian cancer. METHODS: The Society of Gynecologic Oncology (SGO) recently sought and received input from multiple stakeholders including the National Cancer Institute's (NCI) Clinical Therapy Evaluation Program (CTEP), the Food and Drug Administration (FDA), pharmaceutical industry, and patient advocates. This whitepaper is the work product and opinion solely of the SGO. RESULTS: This document summarizes the SGO's interpretation of these meetings and the current regulatory environment where there has been a paucity of recent approvals in the United States. It provides guidance in clinical trial design with the express purpose of encouraging novel drug development in ovarian cancer. Points of emphasis include: ovarian cancer heterogeneity (histologic subtypes and molecular genetic alterations), clinical trial design elements, surrogate as well as composite endpoints, and the four principles of clinical drug development (unmet medical need, discovery, safety, and efficacy). CONCLUSIONS: There has been an evolution in the acceptance of surrogate endpoints depending upon the clinical setting in ovarian cancer. While overall survival (OS) remains the most objective clinical trial endpoint, there is now realization that demanding OS as the primary endpoint has many obstacles. Ovarian cancer is a heterogeneous disease that is now divided by histologic subtypes. Future registration strategies will need to address disease heterogeneity. The exploration of currently acceptable clinical trial endpoints and alternative regulatory strategies will hopefully stimulate interest in novel drug development for patients with ovarian cancer. PMID- 25124161 TI - Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo. AB - OBJECTIVES: Uterine serous carcinoma (USC) represents an aggressive variant of endometrial cancer and accounts for a large proportion of deaths annually. HER2/neu amplification is associated with USC in approximately 30-35% of cases. The objective of this study was to determine the sensitivity of a panel of primary USC cell lines to the small tyrosine kinase inhibitor neratinib, an ErbB1 and HER2 inhibitor, both in vitro and in vivo. METHODS: HER2/neu amplification was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 24 USC cell lines. Flow cytometry was used to determine the effects of neratinib on cell viability, cell cycle distribution and signaling in vitro. Mice harboring HER2/neu amplified xenografts were treated with neratinib to assess the efficacy of the drug in vivo. RESULTS: HER2/neu amplification was noted in 8/24 primary cell lines. Data regarding the efficacy of neratinib was determined using 4 HER2 amplified cell lines and 4 non-amplified cell lines with similar growth rates. Data revealed that cell lines with HER2/neu amplification were exquisitely more sensitive to neratinib compared to non amplified cell lines (mean +/- SEM IC50: 0.011MUM +/- 0.0008 vs. 0.312MUM +/- 0.0456 p<0.0001). Neratinib caused arrest in the G0/G1 phase of the cell cycle and resulted in decreased autophosphorylation of HER2 and activation of S6. Neratinib treated mice harboring xenografts of HER2/neu amplified USC showed delayed tumor growth and improved overall survival compared to vehicle (p=0.0019). CONCLUSIONS: Neratinib may be a potential treatment option for patients harboring HER2/neu amplified USC. Clinical trials for this subset of endometrial cancer patients are warranted. PMID- 25124164 TI - Vitamin E and wound healing: an evidence-based review. AB - Vitamin E has been demonstrated to modulate cellular signalling, gene expression and affect wounds infected with methicillin-resistant Staphylococcus aureus (MRSA), thus influencing wound healing. This evidence-based review aimed to identify and evaluate current research assessing the properties of vitamin E in relation to wound healing, through its role as an antioxidant and its influence on connective tissue growth factor (CTGF), MRSA and gene transcription. Literature dated from 1996 to 2012, published in English, involving either animals or adult humans with an acute or chronic wound were included. The databases that contained relevant articles were narrowed down to four, and a total of 33 identified studies were included. The literature review revealed that there is a significant dearth of robust studies establishing the effects of vitamin E on wound healing, and further research is clearly warranted. PMID- 25124163 TI - Mutations in POLE and survival of colorectal cancer patients--link to disease stage and treatment. AB - Recent molecular profiling studies reported a new class of ultramutated colorectal cancers (CRCs), which are caused by exonuclease domain mutations (EDMs) in DNA polymerase epsilon (POLE). Data on the clinical implications of these findings as to whether these mutations define a unique CRC entity with distinct clinical outcome are lacking. We performed Sanger sequencing of the POLE exonuclease domain in 431 well-characterized patients with microsatellite stable (MSS) CRCs of a population-based patient cohort. Mutation data were analyzed for associations with major epidemiological, clinical, genetic, and pathological parameters including overall survival (OS) and disease-specific survival (DSS). In 373 of 431 MSS CRC, all exons of the exonuclease domain were analyzable. Fifty four mutations were identified in 46 of these samples (12.3%). Besides already reported EDMs, we detected many new mutations in exons 13 and 14 (corresponding to amino acids 410-491) as well as in exon 9 and exon 11 (corresponding to aa 268 303 and aa 341-369). However, we did not see any significant associations of EDMs with clinicopathological parameters, including sex, age, tumor location and tumor stage, CIMP, KRAS, and BRAF mutations. While with a median follow-up time of 5.0 years, survival analysis of the whole cohort revealed nonsignificantly different adjusted hazard ratios (HRs) of 1.35 (95% CI: 0.82-2.25) and 1.44 (0.81-2.58) for OS and DSS indicating slightly impaired survival of patients with EDMs, subgroup analysis for patients with stage III/IV disease receiving chemotherapy revealed a statistically significantly increased adjusted HR (1.87; 95%CI: 1.02-3.44). In conclusion, POLE EDMs do not appear to define an entirely new clinically distinct disease entity in CRC but may have prognostic or predictive implications in CRC subgroups, whose significance remains to be investigated in future studies. PMID- 25124165 TI - Quantifying the influence of the tobacco industry on EU governance: automated content analysis of the EU Tobacco Products Directive. AB - OBJECTIVE: The tobacco industry spends large sums lobbying the European Union (EU) institutions, yet whether such lobbying significantly affects tobacco policy is not well understood. We used novel quantitative text mining techniques to evaluate the impact of industry pressure on the contested EU Tobacco Products Directive revision. DESIGN: Policy positions of 18 stakeholders including the tobacco industry, health NGOs and tobacco retailers were evaluated using their text submissions to EU consultations and impact assessments. Using Wordscores to calculate word frequencies, we developed a scale ranging from 0-tobacco industry to 1-public health organisations, which was then used to track changes in the policy position of the European Commission's 2010 consultation document, its 2012 final proposal and the European Parliament and Council's approved legislation in March 2014. RESULTS: Several stakeholders' positions were closer to the tobacco industry than that of health NGOs, including retailers (omega=0.35), trade unions (omega=0.34) and publishers (omega=0.33 and omega=0.40). Over time the European Commission's position shifted towards the tobacco industry from omega=0.52 (95% CI 0.50 to 0.54) to omega=0.40 (95% CI 0.39 to 0.42). This transition reflected an increasing use of words pertaining to business and the economy in the Commission's document. Our findings were robust to alternative methods of scoring policy positions in EU documents. CONCLUSIONS: Using quantitative text mining techniques, we observed that tobacco industry lobbying activity at the EU was associated with significant policy shifts in the EU Tobacco Products Directive legislation towards the tobacco industry's submissions. In the light of the Framework Convention on Tobacco Control, additional governance strategies are needed to prevent undue influence of the tobacco industry on EU policy making. PMID- 25124166 TI - Mental health/illness and prisons as place: frontline clinicians' perspectives of mental health work in a penal setting. AB - This article takes mental health and prisons as its two foci. It explores the links between social and structural aspects of the penal setting, the provision of mental healthcare in prisons, and mental health work in this environment. This analysis utilises qualitative interview data from prison-based fieldwork undertaken in Her Majesty's Prison Service, England. Two themes are discussed: (1) the desire and practicalities of doing mental health work and (2) prison staff as mental health work allies. Concepts covered include equivalence, training, ownership, informal communication, mental health knowledge, service gatekeepers, case identification, and unmet need. Implications for practice are (1) the mental health knowledge and understanding of prison wing staff could be appraised and developed to improve mental healthcare and address unmet need. Their role as observers and gatekeepers could be considered. (2) The realities of frontline mental health work for clinicians in the penal environment should be embraced and used to produce and implement improved policy and practice guidance, which is in better accord with the actuality of the context - both socially and structurally. PMID- 25124167 TI - Sample size importantly limits the usefulness of instrumental variable methods, depending on instrument strength and level of confounding. AB - OBJECTIVES: Instrumental variable (IV) analysis is promising for estimation of therapeutic effects from observational data as it can circumvent unmeasured confounding. However, even if IV assumptions hold, IV analyses will not necessarily provide an estimate closer to the true effect than conventional analyses as this depends on the estimates' bias and variance. We investigated how estimates from standard regression (ordinary least squares [OLS]) and IV (two stage least squares) regression compare on mean squared error (MSE). STUDY DESIGN: We derived an equation for approximation of the threshold sample size, above which IV estimates have a smaller MSE than OLS estimates. Next, we performed simulations, varying sample size, instrument strength, and level of unmeasured confounding. IV assumptions were fulfilled by design. RESULTS: Although biased, OLS estimates were closer on average to the true effect than IV estimates at small sample sizes because of their smaller variance. The threshold sample size above which IV analysis outperforms OLS regression depends on instrument strength and strength of unmeasured confounding but will usually be large given the typical moderate instrument strength in medical research. CONCLUSION: IV methods are of most value in large studies if considerable unmeasured confounding is likely and a strong and plausible instrument is available. PMID- 25124170 TI - Graphical fault tree analysis for fatal falls in the construction industry. AB - The current study applied a fault tree analysis to represent the causal relationships among events and causes that contributed to fatal falls in the construction industry. Four hundred and eleven work-related fatalities in the Taiwanese construction industry were analyzed in terms of age, gender, experience, falling site, falling height, company size, and the causes for each fatality. Given that most fatal accidents involve multiple events, the current study coded up to a maximum of three causes for each fall fatality. After the Boolean algebra and minimal cut set analyses, accident causes associated with each falling site can be presented as a fault tree to provide an overview of the basic causes, which could trigger fall fatalities in the construction industry. Graphical icons were designed for each falling site along with the associated accident causes to illustrate the fault tree in a graphical manner. A graphical fault tree can improve inter-disciplinary discussion of risk management and the communication of accident causation to first line supervisors. PMID- 25124171 TI - Editorial. Veterinary dermatology over 25 years. PMID- 25124168 TI - Side effects are incompletely reported among systematic reviews in gastroenterology. AB - OBJECTIVES: Systematic reviews are an integral component of evidence-based health care. However, little is known on how well they report the potential harms of interventions. We assessed the reporting of harms in recently published systematic reviews of interventions relevant to clinical gastroenterology. STUDY DESIGN: We identified all systematic reviews of randomized trials of gastroenterology interventions published from 2008 to 2012 in highly cited gastroenterology and general medical journals. We adapted the Consolidated Standards of Reporting Trials guidelines for harms and assessed qualitative and quantitative parameters of harms reporting. Regression analyses determined predictors of more comprehensive harms reporting. RESULTS: In total, 78 systematic reviews were identified, with 72 published in gastroenterology journals and six in general medical journals. Overall, one in three systematic reviews (26/78, 33%) did not refer to harms of the intervention anywhere in the article. Less than half of the studies included adverse events as an outcome measure, and data on absolute rates of adverse events were only provided in 28%. Most (65%) did not include any figures or tables on adverse event; however, all included these on efficacy outcomes (mean, 3 and range, 1-7). Regression analyses indicated that the use of reporting guidelines was significantly associated with better harms reporting (P = 0.04). CONCLUSION: The reporting of harms in gastroenterology systematic reviews is largely inadequate and highly asymmetrical compared with the reporting of benefits. We suggest that review authors routinely assess both efficacy and harms outcomes of an intervention and that reporting guidelines specifically targeting harms reporting be developed. PMID- 25124172 TI - Keratinocyte biology and pathology. PMID- 25124173 TI - Veterinary dermatology and dermatopathology. PMID- 25124169 TI - Intratracheal co-administration of antioxidants and ceftriaxone reduces pulmonary injury and mortality rate in an experimental model of sepsis. AB - BACKGROUND AND OBJECTIVE: Recent studies showed that both sepsis and antibiotic therapy are associated with cell death and linked to reactive oxygen species generation. This study investigated the effects of intratracheal administration of combinations of antioxidants (n-acetyl cysteine (NAC), vitamins C and E) in the treatment of sepsis-induced lung injury. METHODS: Ninety-six male Wistar rats subjected to sepsis were treated with ceftriaxone plus NAC with or without vitamins C and E and compared to appropriate controls. As an index of oxidative damage protein carbonyls, sulfhydryl groups, lipid peroxidation and superoxide anion were measured, as well as superoxide dismutase and catalase. Histopathological alterations and mortality rate were also analyzed. RESULTS: Twenty-four hours after sepsis induction, markers of oxidative stress increased in all lungs examined. Ceftriaxone plus intratracheal combination of NAC, vitamins C and E decreased lung injury in infected animals by reducing superoxide anion production (54%), lipid peroxidation (53%) and protein carbonyl (58%) and restored the redox status (7.5 times). This therapy also reduced the imbalance of antioxidant enzymes activities and attenuated the alveolar architectural disorganization, inflammatory cell infiltration and pulmonary oedema. Survival increased from 66.6% with ceftriaxone to 83.2% with ceftriaxone plus antioxidants. CONCLUSIONS: Ceftriaxone plus intratracheal co-administration of antioxidants provides better protection, by decreasing pulmonary oxidative stress, limiting histophatological alterations and improving survival. Antioxidants should be explored as a co-adjuvant in the treatment of severe lung injury. PMID- 25124175 TI - The 'spore of Malassez' as a canine skin pathogen: lessons from history? PMID- 25124174 TI - Pyoderma, the march of the staphylococci. PMID- 25124176 TI - Insights into immunoglobulin E-mediated late-phase reactions in dogs. PMID- 25124177 TI - An autoimmune subepidermal blistering skin disease in a dog? The odds are that it is not bullous pemphigoid. PMID- 25124178 TI - The secret sits. PMID- 25124179 TI - Orf. PMID- 25124180 TI - Equine dermatology - past, present and future. PMID- 25124181 TI - Systemic signalling in photosynthetic induction of Rumex K-1 (Rumex patientia * Rumex tianschaious) leaves. AB - The rapid induction of photosynthesis is critical for plants under light-fleck environment. Most previous studies about photosynthetic induction focused upon single leaf, but they did not consider the systemic integrity of plant. Here, we verified whether systemic signalling is involved in photosynthetic induction. Rumex K-1 (Rumex patientia * Rumex tianschaious) plants were grown under light fleck condition. After whole night dark adaptation, different numbers of leaves (system leaf or SL) were pre-illuminated with light, and then the photosynthetic induction of other leaves (target leaf or TL) was investigated. This study showed that the pre-illumination of SL promoted photosynthetic induction in TL. This promotion was independent of the number of SL, the light intensity on SL and the distance between SL and TL, indicating that this systemic signalling is non-dose dependent. More interestingly, the photosynthetic induction was promoted by only the pre-illumination of morphological upper leaf rather than the pre-illumination of morphological lower leaf, indicating that the transfer of this signal is directional. The results showed that the transfer of this systemic signalling depends upon the phloem. This systemic signalling helps plants to use light energy more efficiently under light flecks. PMID- 25124182 TI - Motor and cognitive deficits in aged tau knockout mice in two background strains. AB - BACKGROUND: We recently reported that Parkinsonian and dementia phenotypes emerge between 7-12 months of age in tau-/- mice on a Bl6/129sv mixed background. These observations were partially replicated by another group using pure Bl6 background tau-/- mice, but notably they did not observe a cognitive phenotype. A third group using Bl6 background tau-/- mice found cognitive impairment at 20-months of age. RESULTS: To reconcile the observations, here we considered the genetic, dietary and environmental variables in both studies, and performed an extended set of behavioral studies on 12-month old tau+/+, tau+/-, and tau-/- mice comparing Bl6/129sv to Bl6 backgrounds. We found that tau-/- in both backgrounds exhibited reduced tyrosine hydroxylase-positive nigral neuron and impaired motor function in all assays used, which was ameliorated by oral treatment with L-DOPA, and not confounded by changes in body weight. Tau-/- in the C57BL6/SV129 background exhibited deficits in the Y-maze cognition task, but the mice on the Bl6 background did not. CONCLUSIONS: These results validate our previous report on the neurodegenerative phenotypes of aged tau-/- mice, and show that genetic background may impact the extent of cognitive impairment in these mice. Therefore excessive lowering of tau should be avoided in therapeutic strategies for AD. PMID- 25124184 TI - Comparison of five-year outcomes of coronary artery bypass grafting versus percutaneous coronary intervention in patients with left ventricular ejection fractions<=50% versus >50% (from the CREDO-Kyoto PCI/CABG Registry Cohort-2). AB - Coronary heart disease is a major risk factor for left ventricular (LV) systolic dysfunction. However, limited data are available regarding long-term benefits of percutaneous coronary intervention (PCI) in the era of drug-eluting stent or coronary artery bypass grafting (CABG) in patients with LV systolic dysfunction with severe coronary artery disease. We identified 3,584 patients with 3-vessel and/or left main disease of 15,939 patients undergoing first myocardial revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Of them, 2,676 patients had preserved LV systolic function, defined as an LV ejection fraction (LVEF) of >50% and 908 had impaired LV systolic function (LVEF<=50%). In patients with preserved LV function, 5-year outcomes were not different between PCI and CABG regarding propensity score-adjusted risk of all cause and cardiac deaths. In contrast, in patients with impaired LV systolic function, the risks of all-cause and cardiac deaths after PCI were significantly greater than those after CABG (hazard ratio 1.49, 95% confidence interval 1.04 to 2.14, p=0.03 and hazard ratio 2.39, 95% confidence interval 1.43 to 3.98, p<0.01). In both patients with moderate (35%= 3. After controlling for age, preoperative hemoglobin, preoperative albumin, cancer stage, and adverse pathologic features, transfusion of >= 3 (versus 0 to 2) units was associated with poorer OS (P = 0.0006; hazard ratio [HR] = 2.96) and RFS (P = 0.003; HR = 2.35). The rates of wound infection in patients who received 0, 1, 2, or >= 3 units were 13.3%, 21.2%, 33.3%, and 31.2%, respectively. There was a statistically significant difference in wound infection rates between those patients receiving 0 to 1 versus >= 2 units (P = 0.04). CONCLUSIONS: Patients who receive >= 3 units of blood after free tissue transfer for HNC had a significantly increased risk of death after controlling for age, preoperative hemoglobin and albumin, cancer stage, and adverse pathologic features. Increased transfusions are also associated with higher wound infection rates. The increased tendency to transfuse free flap patients in order to maintain a threshold hematocrit may have a detrimental impact on survival and wound infections and should be revisited. PMID- 25124185 TI - An intervention to address secondhand tobacco smoke exposure among nonsmokers hospitalized with coronary heart disease. AB - Secondhand tobacco smoke (SHS) exposure increases nonsmokers' risk of coronary heart disease and worsens outcomes after hospitalization for acute coronary syndrome, but it is rarely addressed in inpatient cardiac care. We developed and assessed a hospital-based intervention to increase nonsmokers' awareness of SHS as a cardiovascular risk factor. Nonsmokers admitted to 2 cardiac units of a large Boston, Massachusetts, hospital were surveyed before (May 2010 to January 2011) and after (November 2011 to March 2012) a system-level nurse-delivered intervention was implemented in October 2011. It consisted of a revised admission form that prompted nurses to document SHS exposure at admission, provide a pamphlet about SHS risks, and advise nonsmokers to make their home and car smoke free. The primary outcome was patients' short-term recall of advice to keep their home and car smoke free. The secondary outcome was patients' awareness of the cardiovascular risk of SHS exposure. We enrolled 190 nonsmokers before and 142 nonsmokers after implementation. Adjusting for group differences, patients admitted after the system change were more likely to recall being asked if a household member smokes (24% vs 10%, adjusted odds ratio [AOR] 3.6, 95% confidence interval [CI] 1.8 to 7.1, p=0.0002) and being advised to keep their home and car smoke free (28% vs 2%, AOR 27.3, 95% CI 7.8 to 95.7, p<0.0001). After the intervention, more patients believed that SHS exposure increased cardiovascular risk for nonsmokers (42% vs 21%, AOR 2.6, 95% CI 1.6 to 4.4) and for themselves (39% vs 22%, AOR 2.2, 95% CI 1.3 to 3.8). In conclusion, a system level intervention in cardiac units successfully increased hospitalized nonsmokers' awareness of the cardiovascular risk of SHS exposure. PMID- 25124187 TI - Frequency and clinical outcomes of ESKAPE bacteremia in solid organ transplantation and the risk factors for mortality. AB - BACKGROUND: Although bacteremias caused by the 6 ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have recently been highlighted as a serious complication in solid organ transplant (SOT), more information is urgently needed. We sought to investigate the frequency and clinical outcomes of ESKAPE bacteremia in SOT and determine the risk factors for mortality. METHODS: A retrospective analysis of bacteremia after SOT was reviewed. Risk factors for mortality caused by ESKAPE bacteremia were identified. RESULTS: Eighty-four episodes of bacteremia were caused by ESKAPE strains. Of these strains, 41 were caused by resistant ESKAPE (rESKAPE) organisms. The only factor for bacteremia related mortality independently associated with ESKAPE was septic shock (odds ratio [OR] = 21.017, 95% confidence interval [CI] = 5.038-87.682, P < 0.001). The factors for bacteremia-related mortality independently associated with rESKAPE bacteremia were septic shock (OR = 16.558, 95% CI = 6.620-104.668, P = 0.003) and age >=40 years (OR = 7.521, 95% CI = 1.196-47.292, P = 0.031). CONCLUSIONS: To improve the outcomes of transplantation, more effective therapeutic treatments are of paramount importance when older SOT recipients with bacteremia due to ESKAPE/rESKAPE organisms present with septic shock. PMID- 25124188 TI - What does your neighbourhood say about you? A study of life expectancy in 1.3 million Swiss neighbourhoods. AB - BACKGROUND: Switzerland had the highest life expectancy at 82.8 years among the Organisation for Economic Co-operation and Development (OECD) countries in 2011. Geographical variation of life expectancy and its relation to the socioeconomic position of neighbourhoods are, however, not well understood. METHODS: We analysed the Swiss National Cohort, which linked the 2000 census with mortality records 2000-2008 to estimate life expectancy across neighbourhoods. A neighbourhood index of socioeconomic position (SEP) based on the median rent, education and occupation of household heads and crowding was calculated for 1.3 million overlapping neighbourhoods of 50 households. We used skew-normal regression models, including the index and additionally marital status, education, nationality, religion and occupation to calculate crude and adjusted estimates of life expectancy at age 30 years. RESULTS: Based on over 4.5 million individuals and over 400,000 deaths, estimates of life expectancy at age 30 in neighbourhoods ranged from 46.9 to 54.2 years in men and from 53.5 to 57.2 years in women. The correlation between life expectancy and neighbourhood SEP was strong (r=0.95 in men and r=0.94 women, both p values <0.0001). In a comparison of the lowest with the highest percentile of neighbourhood SEP, the crude difference in life expectancy from skew-normal regression was 4.5 years in men and 2.5 years in women. The corresponding adjusted differences were 2.8 and 1.9 years, respectively (all p values <0.0001). CONCLUSIONS: Although life expectancy is high in Switzerland, there is substantial geographical variation and life expectancy is strongly associated with the social standing of neighbourhoods. PMID- 25124186 TI - Comparison of stenting and surgical revascularization strategy in non-ST elevation acute coronary syndromes and complex coronary artery disease (from the Milestone Registry). AB - The optimal revascularization strategy in patients with complex coronary artery disease and non-ST-segment elevation acute coronary syndromes is undetermined. In this multicenter, prospective registry, 4,566 patients with non-ST-segment elevation myocardial infarctions, unstable angina, and multivessel coronary disease, including left main disease, were enrolled. After angiography, 3,033 patients were selected for stenting (10.3% received drug-eluting stents) and 1,533 for coronary artery bypass grafting. Propensity scores were used for baseline characteristic matching and result adjustment. Patients selected for percutaneous coronary intervention (PCI) were younger (mean age 64.4+/-10 vs 65.2+/-9 years, p=0.03) and more frequently presented with non-ST-segment elevation myocardial infarctions (32.0% vs 14.5%, p=0.01), cardiogenic shock (1.5% vs 0.7%, p<0.01), and history of PCI (13.1% vs 5.5%, p<0.01) or coronary artery bypass grafting (10.6% vs 4.6%, p<0.01). European System for Cardiac Operative Risk Evaluation scores were higher in PCI patients (5.4+/-2 vs 5.2+/-2, p<0.01). Patients referred for coronary artery bypass grafting more often presented with triple-vessel disease and left main disease (82.2% vs 33.8% and 13.7% vs 2.4%, respectively, p<0.01). After adjustment, 929 well-matched pairs were chosen. Early mortality was lower after PCI before matching (2.1% vs 3.1%, p<0.01), whereas after balancing, there was no difference (2.5% vs 2.8%, p=0.62). Three-year survival was in favor of PCI compared with surgery before (87.5% vs 82.8%, hazard ratio 1.44, 95% confidence interval 1.2 to 1.7, p<0.01) and after (86.4% vs 82.3%, hazard ratio 1.33, 95% confidence interval 1.05 to 1.7, p=0.01). Stenting was associated with improved outcomes in the following subgroups: patients aged >65 years, women, patients with unstable angina, those with European System for Cardiac Operative Risk Evaluation scores>5, those with Thrombolysis In Myocardial Infarction (TIMI) risk scores >4, those receiving drug eluting stents, and those with 2-vessel disease. In conclusion, in patients presenting with non-ST-segment elevation acute coronary syndromes and complex coronary artery disease, immediate stenting was associated with lower mortality risk in the long term compared with surgical revascularization, especially in subgroups at high clinical risk. PMID- 25124189 TI - Risk relativism and physical law. AB - In two 1959 papers, one coauthored, Jerome Cornfield asserts that 'relative' measures are more useful for causal inference while 'absolute' measures are more useful for public health purposes. In one of these papers (the single-authored one), he asks how epidemiology should respond to the fact that its domain is not a highly 'articulated' one-it is not susceptible to being subsumed under general laws. What is the connection between these issues? There has recently been some backlash against 'risk relativism', and Charles Poole has recently dismantled the mathematical argument for the first claim. However the problem with 'Cornfield's Principle' seems to go much deeper. The whole attempt to partition measures into absolute and relative is fundamentally mistaken. Why, then, has it seemed so appealing? Perhaps one reason is the influence that early education in the physical sciences continues to exert on the way epidemiologists think, and their response to the low articulation of their domain of study. PMID- 25124190 TI - Educational differences in mortality and the relative importance of different causes of death: a 7-year follow-up study of Spanish adults. AB - BACKGROUND: The evidence on mortality patterns by education in Spain comes from regional areas. This study aimed to estimate these patterns in the whole Spanish population. METHODS: All citizens aged 25 years and over and residing in Spain in 2001 were followed during 7 years to determine their vital status, resulting in a total of 196,470,401 person-years and 2,379,558 deaths. We estimated the age adjusted total and cause-specific mortality by educational level-primary, lower secondary, upper secondary and university education-and then calculated the relative and absolute measures of inequality in mortality and contribution of the leading causes of death to absolute inequalities. RESULTS: Except for some cancer sites, the mortality rate for the leading causes of death shows an inverse gradient with educational level. The leading causes of death with the highest relative index of inequality ratios were HIV disease (9.81 in women and 11.61 in men), diabetes in women (4.02) and suicide in men (3.52). The leading causes of death that contribute most to the absolute inequality in mortality are cardiovascular diseases (48.8%), respiratory diseases (9.3%) and diabetes mellitus (8.8%) in women, and cardiovascular diseases (20.8%), respiratory diseases (19.8%) and cancer (19.6%) in men. CONCLUSIONS: Although the causes of death with the strongest gradient in mortality rate are HIV disease in both sexes, diabetes mellitus in women and suicide in men, most of the absolute education-related inequalities in total mortality are due to cardiovascular diseases, respiratory diseases and diabetes mellitus in women and to cardiovascular diseases, respiratory diseases and cancer in men. PMID- 25124191 TI - Collective-efficacy as a mediator of the relationship of leaders' personality traits and team performance: A cross-level analysis. AB - The relationship between a leader's personality and his team's performance has been established in organisational research, but the underlying process and mechanism responsible for this effect have not been fully explored. Both the traditional multiple linear regression and the multilevel structural equation model approaches were used in this study to test a proposed mediating model of subordinates' perception of collective efficacy between leader personality and team performance. The results show that the team leader's extraversion and conscientiousness personality traits were related positively to both the team average (individual) perception of collective efficacy and team performance, and the collective efficacy mediated the relationship of the leader's personality traits and team performance. This study also discusses how Chinese cultural elements play a role in such a mediating model. PMID- 25124192 TI - Identification and characterisation of multiple glutathione S-transferase genes from the diamondback moth, Plutella xylostella. AB - BACKGROUND: The diamondback moth (DBM), Plutella xylostella, is one of the most harmful insect pests on crucifer crops worldwide. In this study, 19 cDNAs encoding glutathione S-transferases (GSTs) were identified from the genomic and transcriptomic database for DBM (KONAGAbase) and further characterized. RESULTS: Phylogenetic analysis showed that the 19 GSTs were classified into six different cytosolic classes, including four in delta, six in epsilon, three in omega, two in sigma, one in theta and one in zeta. Two GSTs were unclassified. RT-PCR analysis revealed that most GST genes were expressed in all developmental stages, with higher expression in the larval stages. Six DBM GSTs were expressed at the highest levels in the midgut tissue. Twelve purified recombinant GSTs showed varied enzymatic properties towards 1-chloro-2,4-dinitrobenzene and glutathione, whereas rPxGSTo2, rPxGSTz1 and rPxGSTu2 had no activity. Real-time quantitative PCR revealed that expression levels of the 19 DBM GST genes were varied and changed after exposure to acephate, indoxacarb, beta-cypermethrin and spinosad. PxGSTd3 was significantly overexpressed, while PxGSTe3 and PxGSTs2 were significantly downregulated by all four insecticide exposures. CONCLUSION: The changes in DBM GST gene expression levels exposed to different insecticides indicate that they may play individual roles in tolerance to insecticides and xenobiotics. PMID- 25124194 TI - The use of chaperones during sensitive examinations and treatments. PMID- 25124195 TI - Harvesting solar light with crystalline carbon nitrides for efficient photocatalytic hydrogen evolution. AB - Described herein is the photocatalytic hydrogen evolution using crystalline carbon nitrides (CNs) obtained by supramolecular aggregation followed by ionic melt polycondensation (IMP) using melamine and 2,4,6-triaminopyrimidine as a dopant. The solid state NMR spectrum of (15)N-enriched CN confirms the triazine as a building unit. Controlling the amount and arrangements of dopants in the CN structure can dramatically enhance the photocatalytic performance for H2 evolution. The polytriazine imide (PTI) exhibits the apparent quantum efficiency (AQE) of 15% at 400 nm. This method successfully enables a substantial amount of visible light to be harvested for H2 evolution, and provides a promising route for the rational design of a variety of highly active crystalline CN photocatalysts. PMID- 25124193 TI - Implications of the Wnt5a/CaMKII pathway in retinoic acid-induced myogenic tongue abnormalities of developing mice. AB - Although proper tongue development is relevant to other structures in the craniofacial region, the molecular details of muscle development in tongue remain poorly understood. Here, we report that pregnant mice treated with retinoic acid (+RA) produce embryos with tongue malformation and a cleft palate. Histological analyses revealed that at E14.5, the tongues of +RA fetuses failed to descend and flatten. Ultrastructural analysis showed that at perinatal stage E18.5, the myofilaments failed to form normal structures of sarcomeres, and arranged disorderly in the genioglossus. The proliferation and levels of myogenic determination markers (Myf5 and MyoD) and myosin in the genioglossus were profoundly reduced. Wnt5a and Camk2d expressions were down-regulated, while levels of Tbx1, Ror2, and PKCdelta were up-regulated in the tongues of +RA fetuses. In mock- and Wnt5a-transfected C2C12 (Wnt5a-C2C12) cells, Wnt5a overexpression impaired proliferation, and maintained Myf5 at a relative high level after RA treatment. Furthermore, Wnt5a overexpression positively correlated with levels of Camk2d and Ror2 in C2C12 cells after RA exposure. These data support the hypothesis that the Wnt5a/CaMKII pathway is directly involved in RA induced hypoplasia and disorder of tongue muscles. PMID- 25124196 TI - [Prevalence of uterine fibroids in France and impact on quality of life: results of a survey among 2500 women between 30-55 years]. AB - OBJECTIVES: To evaluate the prevalence of symptomatic uterine fibroid in France, related symptoms and its impact on quality of life. MATERIALS AND METHODS: Online prospective survey from December 2012 to February 2013 using two questionnaires on 2498 women aged between 30 and 55 years old and representatives of the feminine population. RESULTS: On the studied population, 220 women presented a symptomatic uterine fibroid representing a prevalence of 8.8%. 163 women (73.7%) presented bleedings associated or not with pain, and 58 (26.3%) suffered from pain only. For 77 (34.9%) women, the symptoms preceded the diagnostic and the mean delay between first symptoms and diagnostic was 2.22 years (ET : 3.56). At the time of the survey, 144 (65%) women with symptomatic uterine fibroid were followed by a physician (a gynecologist in 91.6% (n=132)), and 110 (49.7%) evaluated their pain as severe or extremely severe and 178 (80.6%) were bothered by their symptoms in their everyday life. CONCLUSION: This analysis shows a strong prevalence for symptomatic uterine fibroid with a major impact on the quality of life. PMID- 25124197 TI - Score test variable screening. AB - Variable screening has emerged as a crucial first step in the analysis of high throughput data, but existing procedures can be computationally cumbersome, difficult to justify theoretically, or inapplicable to certain types of analyses. Motivated by a high-dimensional censored quantile regression problem in multiple myeloma genomics, this article makes three contributions. First, we establish a score test-based screening framework, which is widely applicable, extremely computationally efficient, and relatively simple to justify. Secondly, we propose a resampling-based procedure for selecting the number of variables to retain after screening according to the principle of reproducibility. Finally, we propose a new iterative score test screening method which is closely related to sparse regression. In simulations we apply our methods to four different regression models and show that they can outperform existing procedures. We also apply score test screening to an analysis of gene expression data from multiple myeloma patients using a censored quantile regression model to identify high-risk genes. PMID- 25124198 TI - Rapid separation and characterization of diterpenoid alkaloids in processed roots of Aconitum carmichaeli using ultra high performance liquid chromatography coupled with hybrid linear ion trap-Orbitrap tandem mass spectrometry. AB - The lateral root of Aconitum carmichaeli, a popular traditional Chinese medicine, has been widely used to treat rheumatic diseases. For decades, diterpenoid alkaloids have dominated the phytochemical and biomedical research on this plant. In this study, a rapid and sensitive method based on ultra high performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry was developed to characterize the diterpenoid alkaloids in Aconitum carmichaeli. Based on an optimized chromatographic condition, more than 120 diterpenoid alkaloids were separated with good resolution. Using a systematic strategy that combines high resolution separation, highly accurate mass measurements and a good understanding of the diagnostic fragment-based fragmentation patterns, these diterpenoid alkaloids were identified or tentatively identified. The identification of these chemicals provided essential data for further phytochemical studies and toxicity research of Aconitum carmichaeli. Moreover, the ultra high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry platform was an effective and accurate tool for rapid qualitative analysis of secondary metabolite productions from natural resources. PMID- 25124200 TI - Adolescent health care maintenance in a teen-friendly clinic. AB - Adolescence is marked by complex physical, cognitive, social, and emotional development, which can be stressful for families and adolescents. Before the onset of puberty, providers should clearly lay the groundwork for clinical care and office visits during the adolescent years. This article addresses the guidelines and current legal standards for confidentiality in adolescent care, the most frequently used psychosocial screening tools, and current recommendations for preventive health services and immunizations. Through the creation of teen-friendly clinics, primary care providers are well positioned to offer guidance and support to teens and their parents during this time of transition and growth. PMID- 25124199 TI - Knowing who to trust: exploring the role of 'ethical metadata' in mediating risk of harm in collaborative genomics research in Africa. AB - BACKGROUND: The practice of making datasets publicly available for use by the wider scientific community has become firmly integrated in genomic science. One significant gap in literature around data sharing concerns how it impacts on scientists' ability to preserve values and ethical standards that form an essential component of scientific collaborations. We conducted a qualitative sociological study examining the potential for harm to ethnic groups, and implications of such ethical concerns for data sharing. We focused our empirical work on the MalariaGEN Consortium, one of the first international collaborative genomics research projects in Africa. METHODS: We conducted a study in three MalariaGEN project sites in Kenya, the Gambia, and the United Kingdom. The study entailed analysis of project documents and 49 semi-structured interviews with fieldworkers, researchers and ethics committee members. RESULTS: Concerns about how best to address the potential for harm to ethnic groups in MalariaGEN crystallised in discussions about the development of a data sharing policy. Particularly concerning for researchers was how best to manage the sharing of genomic data outside of the original collaboration. Within MalariaGEN, genomic data is accompanied by information about the locations of sample collection, the limitations of consent and ethics approval, and the values and relations that accompanied sample collection. For interviewees, this information and context were of important ethical value in safeguarding against harmful uses of data, but is not customarily shared with secondary data users. This challenged the ability of primary researchers to protect against harmful uses of 'their' data. CONCLUSION: We identified three protective mechanisms--trust, the existence of a shared morality, and detailed contextual understanding--which together might play an important role in preventing the use of genomic data in ways that could harm the ethnic groups included in the study. We suggest that the current practice of sharing of datasets as isolated objects rather than as embedded within a particular scientific culture, without regard for the normative context within which samples were collected, may cause ethical tensions to emerge that could have been prevented or addressed had the 'ethical metadata' that accompanies genomic data also been shared. PMID- 25124201 TI - Adolescent growth and development. AB - Adolescence is a developmental stage defined by physical and psychosocial maturation. This article reviews normal pubertal development and the evaluation and management of adolescents with suspected pubertal abnormalities and provides an overview of adolescent psychosocial development. PMID- 25124202 TI - Parents and family matter: strategies for developing family-centered adolescent care within primary care practices. AB - Healthy adolescent development and successful transition to adulthood begins in the family. Supporting families in their communities and cultures ultimately makes this support system stronger. Parenting adolescents is described as the most challenging life stage for parents. Primary care providers are in an ideal position to support families with teens. This article reviews stressors, recommends strength-based strategies, describes how health care delivery systems can be organized to address the needs of adolescents and their families, shares a case study of a family-oriented, youth-friendly primary care clinic, and provides practical strategies for developing family-centered adolescent care within primary care practices. PMID- 25124203 TI - Primary care for adolescents with developmental disabilities. AB - Disability is a natural part of the human experience. To maximize potential, adolescents with disabilities require multidisciplinary transition planning and life-skill training. Health care professionals can reduce barriers to accessing health care. They can encourage self-determination and connect patients to self advocacy organizations. They can facilitate smooth transitions to adult health care services. Careful descriptions of a patient's baseline traits and function are critical, not only to assist in person centered planning processes, but to ensure that new caregivers and clinicians have the information they need to recognize changes in function or behavior that can signal illness. PMID- 25124204 TI - Body image and health: eating disorders and obesity. AB - Eating behavior in adolescents can be as high risk as other behaviors that arise during this period and can have serious health consequences. This article presents a framework for screening and treatment of abnormal adolescent eating behavior by the primary care provider. A review of the types of disordered eating is presented along with suggested ways to screen. Indications for subspecialty eating disorder referrals and key aspects of screening and intervention in adolescent obesity and eating disorders are also reviewed. Specific attention is paid to the aspects of care that can be provided in primary care and multidisciplinary care. PMID- 25124206 TI - Teens, technology, and health care. AB - Teens are avid users of new technologies and social media. Nearly 95% of US adolescents are online at least occasionally. Health care professionals and organizations that work with teens should identify online health information that is both accurate and teen friendly. Early studies indicate that some of the new health technology tools are acceptable to teens, particularly texting, computer based psychosocial screening, and online interventions. Technology is being used to provide sexual health education, medication reminders for contraception, and information on locally available health care services. This article reviews early and emerging studies of technology use to promote teen health. PMID- 25124205 TI - Common issues encountered in adolescent sports medicine: guide to completing the preparticipation physical evaluation. AB - Participation in athletic activities among children and adolescents is on the rise in the United States. Approximately 35 million children ages 5 to 18 play organized sports each year. High school athletes suffer approximately 2 million injuries per year, resulting in 500,000 doctor visits and 30,000 hospitalizations. In addition, early specialization in sports has led to increased incidence of overuse injury in adolescents. Head injuries among adolescents are also on the rise. Primary care providers are called on to complete preparticipation evaluations and to see adolescents with acute injuries. The goal of this article is to discuss these issues common to adolescent athletes. PMID- 25124207 TI - Adolescent substance involvement use and abuse. AB - Substance use in adolescence is common, but not all use indicates a substance use disorder. The primary care provider has an essential role in screening for substance involvement, assessing the level of substance use and its impact on function, and engaging in a brief intervention to encourage and support behavioral change related to substance use. This article summarizes the literature on adolescent vulnerability to substance use disorders and their impact on adolescent health and well-being. Practical concrete suggestions for approaches to screening, brief interventions, and referral to treatment provide a stepwise approach to adolescent substance use assessment and intervention. PMID- 25124208 TI - Mood disorders in adolescents: diagnosis, treatment, and suicide assessment in the primary care setting. AB - The primary care setting is considered the entry point of adolescents with mental illness in the health care system. This article informs primary care providers about the diagnostic features and differential of mood disorders in adolescents, screening and assessment, as well as evidence-based psychosocial and psychopharmacologic therapies. The article also provides a framework for decision making regarding initiating treatment in the primary care setting and referral to mental health services. Furthermore, the article highlights the importance of the collaboration between primary care and mental health providers to facilitate engagement of adolescents with mood disorders and adherence to treatment. PMID- 25124209 TI - Adolescent pregnancy and contraception. AB - 7% of US teen women became pregnant in 2008, totaling 750,000 pregnancies nationwide. For women ages 15 to 19, 82% of pregnancies are unintended. Adolescents have a disproportionate risk of medical complications in pregnancy. Furthermore, adolescent parents and their infants both tend to suffer poor psychosocial outcomes. Preventing unintended and adolescent pregnancies are key public health objectives for Healthy People 2020. Screening for sexual activity and pregnancy risk should be a routine part of all adolescent visits. Proven reductions in unintended pregnancy in teens are attained by providing access to contraception at no cost and promoting the most-effective methods. PMID- 25124210 TI - Common sexually transmitted infections in adolescents. AB - Adolescents are often at higher risk for acquiring sexually transmitted infections (STIs). Medical providers should be alert for both asymptomatic and symptomatic STIs, and follow appropriate screening guidelines. Moreover, providers need to know how to best administer adolescent-friendly confidential care, treatment, and health education in the primary care setting. This article addresses the most common adolescent STIs and pertinent recommendations for screening, diagnosis, and management of infections, in addition to a brief focused discussion on human immunodeficiency virus and adolescents. PMID- 25124211 TI - Sexual minority youth. AB - This article provides an overview of the medical and mental health needs of the lesbian, gay, bisexual, and transgender (LGBT) youth population. Information is reviewed regarding both primary medical care and the special health risks that these youth face. Providers are introduced to the concept that societal and internalized homophobia lead directly to certain health disparities, including substance use, school and family rejection, depression, and increased sexually transmitted infection acquisition. This article familiarizes the primary care practitioner with the health care needs of the LGBT population and the research behind the various recommendations for caring for these youth. PMID- 25124212 TI - Adolescent interpersonal violence: implications for health care professionals. AB - Violence involvement is a leading cause of morbidity and mortality among adolescents. This review provides a summary of the burden of adolescent violence and violence-related behavior, risk, and protective factors for violence outcomes. The importance of screening for violence involvement in the primary care setting and examples of online resources to support providers in advocating, assessing, and intervening on behalf of youth are also reviewed. The article draws attention to bullying and dating/relationship violence, not as new forms of violence-related behavior, but as behaviors with health outcomes that have recently received increased attention. PMID- 25124213 TI - Health care for youth involved with the correctional system. AB - Adolescents with involvement in the correctional system have significant health risks and needs. Professional guidelines and policies related to health services in correctional settings can help health care providers who work in youth detention facilities and those who see youth for follow-up care after incarceration. Several challenges exist to providing care in detention facilities, but overcoming these barriers to optimally serve youth is critical. When youth are released to their homes, community providers must understand the extent of care offered in detention facilities, the unique considerations for youth on probation, and the aspects of follow-up care that should be addressed. PMID- 25124214 TI - Know your audience. Adolescent medicine. PMID- 25124215 TI - Adolescent medicine. Preface. PMID- 25124216 TI - Axial level-specific regulation of neuronal development: lessons from PITX2. AB - Transcriptional regulation of gene expression is vital for proper control of proliferation, migration, differentiation, and survival of developing neurons. Pitx2 encodes a homeodomain transcription factor that is highly expressed in the developing and adult mammalian brain. In humans, mutations in PITX2 result in Rieger syndrome, characterized by defects in the development of the eyes, umbilicus, and teeth and variable abnormalities in the brain, including hydrocephalus and cerebellar hypoplasia. Alternative splicing of Pitx2 in the mouse results in three isoforms, Pitx2a, Pitx2b, and Pitx2c, each of which is expressed symmetrically along the left-right axis of the brain throughout development. Here, we review recent evidence for axial and brain region-specific requirements for Pitx2 during neuronal migration and differentiation, highlighting known isoform contributions. PMID- 25124217 TI - The ontogenetic origins of skull shape disparity in the Triturus cristatus group. AB - Comparative studies of ontogenies of closely related species provide insights into the mechanisms responsible for morphological diversification. Using geometric morphometrics, we investigated the ontogenetic dynamics of postlarval skull shape and disparity in three closely related crested newt species. The skull shapes of juveniles just after metamorphosis (hereafter metamorphs) and adult individuals were sampled by landmark configurations that describe the shape of the dorsal and ventral side of the newt skull, and analyzed separately. The three species differ in skull size and shape in metamorphs and adults. The ontogenies of dorsal and ventral skull differ in the orientation but not lengths of the ontogenetic trajectories. The disparity of dorsal skull shape increases over ontogeny, but that of ventral skull shape does not. Thus, modifications of ontogenetic trajectories can, but need not, increase the disparity of shape. In species with biphasic life-cycles, when ontogenetic trajectories for one stage can be decoupled from those of another, increases and decreases in disparity are feasible, but our results show that they need not occur. PMID- 25124218 TI - Cardiac magnetic resonance versus transthoracic echocardiography for the assessment and quantification of aortic regurgitation in patients undergoing transcatheter aortic valve implantation. AB - BACKGROUND: The transthoracic echocardiographic (TTE) evaluation of the severity of residual aortic regurgitation (AR) following transcatheter aortic valve implantation (TAVI) has been controversial and lacks validation. OBJECTIVES: This study sought to compare TTE and cardiac magnetic resonance (CMR) for assessment of AR in patients undergoing TAVI with a balloon-expandable valve. METHODS: TTE and CMR exams were performed pre-TAVI in 50 patients and were repeated postprocedure in 42 patients. All imaging data were analysed in centralised core laboratories. RESULTS: The severity of native AR as determined by multiparametric TTE approach correlated well with the regurgitant volume and regurgitant fraction determined by CMR prior to TAVI (Rs=0.79 and 0.80, respectively; p<0.001 for both). However, after TAVI, the correlation between the prosthetic AR severity assessed by TTE and regurgitant volume and fraction measured by CMR was only modest (Rs=0.59 and 0.59, respectively; p<0.001 for both), with an underestimation of AR severity by TTE in 61.9% of patients (1 grade in 59.5%). The TTE jet diameter in parasternal view and the multiparametric approach (Rs=0.62 and 0.59, respectively; both with p<0.001) showed the best correlation with CMR regurgitant fraction post-TAVI. The circumferential extent of prosthetic paravalvular regurgitation showed a poor correlation with CMR regurgitant volume and fraction (Rs=0.32, p=0.084; Rs=0.36, p=0.054, respectively). CONCLUSIONS: The severity of AR following TAVI with a balloon-expandable valve was underestimated by echocardiography as compared with CMR. The jet diameter, but not the circumferential extent of the leaks, and the multiparametric echocardiography integrative approach best correlated with CMR findings. These results provide important insight into the evaluation of AR severity post-TAVI. PMID- 25124219 TI - Age-related differences in the activity of arterial mineral deposition and regional bone metabolism: a 18F-sodium fluoride positron emission tomography study. AB - Functional (18)F-fluoride PET demonstrated an inverse relationship between the activity of arterial mineral deposition and regional bone metabolism. While bone metabolism decreases with age, the activity of arterial mineral deposition increases. INTRODUCTION: The extent of arterial calcification increases with age, whereas bone mineral density decreases, evidencing a well-known inverse correlation on morphological basis. The aim of this study was to evaluate the functional relationship between the activity of arterial mineral deposition and regional bone metabolism as assessed by (18)F-sodium fluoride (NaF) PET/CT. METHODS: Three hundred four subjects were examined by (18)F-NaF PET/CT. Tracer accumulation in the femoral arteries was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio). Uptake was compared with cardiovascular risk factors (RFs), calcified plaque burden, and regional bone metabolism as assessed by PET/CT. RESULTS: The activity of arterial mineral deposition significantly increased with age (p < 0.001), whereas regional bone metabolism significantly decreased (p < 0.001). There was a significant inverse correlation between bone metabolism and arterial mineral deposition (unadjusted, p < 0.001); that association was not significant (p = 0.79) when controlled for age and other RFs. Both high activity of arterial mineral deposition and low bone metabolism were significantly associated with cardiovascular events and other RFs. CONCLUSION: (18)F-NaF PET/CT provides a tool to visualize and quantify the activity of arterial mineral deposition and regional bone metabolism. In this study, we observed an inverse correlation between the activity of arterial mineral deposition and regional bone metabolism. While the activity of arterial mineral deposition significantly increases with age, regional bone metabolism decreases. PMID- 25124220 TI - Utility of an Australasian registry for children undergoing radiation treatment. AB - INTRODUCTION: The aim of this study was to evaluate the utility of an Australasian registry ('the Registry') for children undergoing radiation treatment (RT). METHODS: Children under the age of 16 years who received a course of radiation between January 1997 and December 2010 and were enrolled on the Registry form the subjects of this study. RESULTS: A total of 2232 courses of RT were delivered, predominantly with radical intent (87%). Registrations fluctuated over time, but around one-half of children diagnosed with cancer undergo a course of RT. The most prevalent age range at time of RT was 10-15 years, and the most common diagnoses were central nervous system tumours (34%) and acute lymphoblastic leukaemia (20%). CONCLUSIONS: The Registry provides a reflection of the patterns of care of children undergoing RT in Australia and a mechanism for determining the resources necessary to manage children by RT (human, facilities and emerging technologies, such as proton therapy). It lacks the detail to provide information on radiotherapy quality and disease outcomes which should be the subject of separate audit studies. The utility of the Registry has been hampered by its voluntary nature and varying needs for consent. Completion of registry forms is a logical requirement for inclusion in the definition of a subspecialist in paediatric radiation oncology. PMID- 25124221 TI - Site-directed delivery of nitric oxide to cancers. AB - Nitric oxide (NO) is a reactive gaseous free radical which mediates numerous biological processes. At elevated levels, NO is found to be toxic to cancers and hence, a number of strategies for site-directed delivery of NO to cancers are in development during the past two decades. More recently, the focus of research has been to, in conjunction with other cancer drugs deliver NO to cancers for its secondary effects including inhibition of cellular drug efflux pumps. Among the various approaches toward site-selective delivery of exogenous NO sources, enzyme activated nitric oxide donors belonging to the diazeniumdiolate category afford unique advantages including exquisite control of rates of NO generation and selectivity of NO production. For this prodrug approach, enzymes including esterase, glutathione/glutathione S-transferase, DT-diaphorase, and nitroreductase are utilized. Here, we review the design and development of various approaches to enzymatic site-directed delivery of NO to cancers and their potential. PMID- 25124224 TI - Ocular pterygium--digital keloid dysplasia. AB - We describe an adolescent Peruvian male with marked, aggressive ingrowth of conjunctiva (pterygium-like) over the cornea associated with keloid formation on his distal limbs. He has in addition camptodactyly of all fingers and to some extent of his toes, and unusual skin pigmentations. He resembles an earlier described family from Norway in which a mother and two children showed a similar combination of signs. We present the follow-up of the Norwegian family. The entity resembles the Penttinen syndrome but can be differentiated due to the early aging in the latter, which is lacking in the presently reported entity. We suggest naming this entity ocular pterygium-digital keloid dysplasia. The condition follows likely an autosomal dominant pattern of inheritance. PMID- 25124225 TI - Molecularly imprinted polymer as in-line concentrator in capillary electrophoresis coupled with mass spectrometry for the determination of quinolones in bovine milk samples. AB - In this work molecularly imprinted polymers have been evaluated as sorbent for the construction of an in-line solid phase extraction analyte concentrator in capillary electrophoresis coupled with mass spectrometry for the determination of the eight regulated veterinary quinolones in bovine milk samples. Different parameters affecting the analyte concentrator performance, such as sample pH, volume and composition of the elution plug and injection time, were studied. Sample volumes of 22MUL (2bar for 15min) were loaded on the MISPE microcartridge and the retained analytes were eluted by injecting a plug of MeOH/H2O/NH3 (60/37/3 by volume) for 125s at 50mbar (60nL). The proposed method is simple for the monitoring of these antibiotic residues in milk samples, allowing the direct injection of the samples with minimum sample pretreatment, achieving limits of detection between 3.8 and 4.7MUgkg(-1) and unequivocal identification of the compounds working in tandem mass spectrometry. Recoveries ranging from 70.0 to 102.3% were obtained and satisfactory intra-day and inter-day RSDs were achieved (<=12% and 15% respectively). Reproducibility among different constructed analyte concentrators showed RSD<=11%. PMID- 25124226 TI - Simultaneous determination of nickel, cobalt and mercury ions in water samples by solid phase extraction using multiwalled carbon nanotubes as adsorbent after chelating with sodium diethyldithiocarbamate prior to high performance liquid chromatography. AB - Multiwalled carbon nanotubes (MWNTs) have been widely used for the enrichment of trace important pollutants in environment because of its large specific surface area, high extraction efficiency, and easy operation. In this study, a solid phase extraction method was established to determine nickel (Ni(2+)), cobalt (Co(2+)) and mercury (Hg(2+)) ions using MWNTs as the adsorbent and sodium diethyldithiocarbamate (DDTC) as the chelating agent. The final analysis was performed on a high performance liquid chromatography (HPLC). The factors that may influence the extraction efficiency were optimized in detail including the type and volume of elution solvent, sample pH, volume of chelating agent solution, and volume of sample solution, etc. The experimental results indicated that good linear relationship between peak area and the concentration of the ions was achieved in the range of 0.1-100MUgL(-1), 0.1-50MUgL(-1), and 2.7-300MUgL(-1) for Ni(2+), Co(2+), and Hg(2+), respectively. The precision was determined by calculating the relative standard deviation (R.S.D.) values that were in the range of 6.2-11.7% under the optimal conditions. The detection limits of Ni(2+), Co(2+), and Hg(2+) were in the range of 0.04-0.9MUgL(-1) (S/N=3). The presented method was applied for the determination of the metal ions mentioned above in real water samples, and satisfied results were achieved. All these indicated that proposed method will be a good alternative tool for monitoring the target ions in environmental samples in the future. PMID- 25124227 TI - Ionic liquid-assisted liquid-phase microextraction based on the solidification of floating organic droplets combined with high performance liquid chromatography for the determination of benzoylurea insecticide in fruit juice. AB - A green, simple, and efficient method, ionic liquid-assisted liquid-liquid microextraction based on the solidification of floating organic droplets (ILSFOD LLME) collected via a bell-shaped collection device (BSCD) coupled to high performance liquid chromatography with a variable-wavelength detector, was developed for the preconcentration and analysis of seven benzoylurea insecticides (BUs) in fruit juice. In the proposed method, the low-density solvent 1-dodecanol and the ionic liquid trihexyl(tetradecyl)phosphonium hexafluorophosphate ([P14, 6, 6, 6]PF6) were used as extractant. The extraction solvent droplet was easily collected and separated by the BSCD without centrifugation. The experimental parameters were optimized by the one-factor-at-a-time approach and were followed using an orthogonal array design. The results indicated the different effects of each parameter for extraction efficiency. Under the optimal conditions in the water model, the limits of detection for the analytes varied from 0.03 to 0.28MUgL(-1). The enrichment factors ranged from 160 to 246. Linearities were achieved for hexaflumuron and flufenoxuron in the range of 0.5-500MUgL(-1), for triflumuron, lufenuron and diafenthiuron in the range of 1-500MUgL(-1), and for diflubenzuron and chlorfluazuron in the range of 5-500MUgL(-1); the correlation coefficients for the BUs ranged from 0.9960 to 0.9990 with recoveries of 75.6 113.9%. Finally, the developed technique was successfully applied to real fruit juice with acceptable results. The relative standard deviations (RSDs) of the seven BUs at two spiked levels (50 and 200MUgL(-1)) varied between 0.1% and 7.3%. PMID- 25124228 TI - Determination of levamisole and tetramisole in seized cocaine samples by enantioselective high-performance liquid chromatography and circular dichroism detection. AB - Levamisole, an anthelmintic drug, has been increasingly employed as an adulterant of illicit street cocaine over the last decade; recently, the use of tetramisole, the racemic mixture of levamisole and its enantiomer dexamisole, was also occasionally observed. A new enantioselective high-performance liquid chromatography (HPLC) method, performed on cellulose tris(3,5 dimethylphenylcarbamate) chiral stationary phases in normal-phase mode, was validated to determine the enantiomeric composition of tetramisole enantiomers in seized cocaine samples. Furthermore, the hyphenation of the validated HPLC method with a circular dichroism (CD) detection system allowed the direct determination of elution order and a selective monitoring of levamisole and dexamisole in the presence of possible interferences. The method was applied to the identification and quantitation of the two enantiomers of tetramisole in seized street cocaine samples. PMID- 25124229 TI - Chiral chromatography-tandem mass spectrometry applied to the determination of pro-resolving lipid mediators. AB - Pro-resolving lipid mediators are a class of endogenously synthesized molecules derived from different fatty acids, such as arachidonic, docosahexaenoic or eicosapentaenoic acid, which are derived into four different product families: lipoxins, resolvins, maresins and protectins. For quantitation of these compounds, a sensitive, selective and robust liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantitation of lipoxin A4, 6-epi-lipoxin A4, lipoxin B4 and lipoxin A5, the D-series resolvins D1 and D2 as well as aspirin-triggered lipoxin A4 and resolvin D1, maresin and protectin and the pathway markers 17(S)-hydroxy-docosahexaenoic acid and 17(R)-hydroxy-docosahexaenoic acid in cell culture supernatants. For this purpose, a chiral column was connected in series with a reversed-phase column to achieve efficient analyte separation and high sensitivity. Sample pre-treatment included a fast and simple liquid-liquid extraction procedure. Limits of quantitation in the range of 0.1-0.5ng/mL cell culture media, absolute recoveries between 90 and 115%, intra- and interday precision of less than 13% and an accuracy of less than 11% were obtained. Stability of the samples after 60 days storage at -80 degrees C, three freeze/thaw cycles and 4h at room temperature has been demonstrated for all analytes. Sample extracts can be stored at 7 degrees C for 24h without degradation of the analytes. Deviations of less than 13% in the accuracy, evaluated in terms of relative error, were obtained. The suitability of the method has been demonstrated in cell culture supernatants of human polymorphonuclear leukocytes, stimulated with 15R-hydroxy-eicosatetraenoic acid and in cell culture media of human polymorphonuclear leukocytes co-incubated with human platelets. From all studied analytes, lipoxin A4 and 6-epi-lipoxin A4 were found in cell culture media under both incubation conditions, while 15-epi lipoxin A4 was additionally detected in cell culture supernatants of polymorphonuclear leukocytes stimulated with 15R-hydroxy-eicosatetraenoic acid. PMID- 25124231 TI - Survival disparities between Maori and non-Maori men with prostate cancer in New Zealand. AB - OBJECTIVE: To examine temporal trends and current survival differences between Maori and non-Maori men with prostate cancer in New Zealand (NZ). PATIENTS AND METHODS: A cohort of 37,529 men aged >= 40 years diagnosed with prostate cancer between 1996 and 2010 was identified from the New Zealand Cancer Registry and followed until 25 May 2011. Cause of death was obtained from the Mortality Collection by data linkage. Survival for Maori compared with non-Maori men was estimated using the Kaplan-Meier method, and Cox proportional hazard regression models, adjusted for age, year of diagnosis, socioeconomic deprivation and rural/urban residence. RESULTS: The probability of surviving was significantly lower for Maori compared with non-Maori men at 1, 5 and 10 years after diagnosis. Maori men were more likely to die from any cause [adjusted hazard ratio (aHR) 1.84, 95% confidence interval (CI) 1.72-1.97] and from prostate cancer (aHR 1.94, 95% CI 1.76- 2.14). The aHR of prostate cancer death for Maori men diagnosed with regional extent was 2.62-fold (95% CI 1.60-4.31) compared with non-Maori men. The survival gap between Maori and non-Maori men has not changed throughout the study period. CONCLUSION: Maori men had significantly poorer survival than non-Maori, particularly when diagnosed with regional prostate cancer. Despite improvements in survival for all men diagnosed after 2000, the survival gap between Maori and non-Maori men has not been reduced with time. Differences in prostate cancer detection and management, partly driven by higher socioeconomic deprivation in Maori men, were identified as the most likely contributors to ethnic survival disparities in NZ. PMID- 25124232 TI - Equivalent input produces different output in the UniFrac significance test. AB - BACKGROUND: UniFrac is a well-known tool for comparing microbial communities and assessing statistically significant differences between communities. In this paper we identify a discrepancy in the UniFrac methodology that causes semantically equivalent inputs to produce different outputs in tests of statistical significance. RESULTS: The phylogenetic trees that are input into UniFrac may or may not contain abundance counts. An isomorphic transform can be defined that will convert trees between these two formats without altering the semantic meaning of the trees. UniFrac produces different outputs for these equivalent forms of the same input tree. This is illustrated using metagenomics data from a lake sediment study. CONCLUSIONS: Results from the UniFrac tool can vary greatly for the same input depending on the arbitrary choice of input format. Practitioners should be aware of this issue and use the tool with caution to ensure consistency and validity in their analyses. We provide a script to transform inputs between equivalent formats to help researchers achieve this consistency. PMID- 25124233 TI - Simulations of potentials of mean force for separating a leucine zipper dimer and the basic region of a basic region leucine zipper dimer. AB - Basic region leucine zipper (bZIP) transcription factors involved in DNA recognition are dimeric proteins. The monomers consist of two subdomains, a leucine zipper sequence responsible for dimerization and a highly basic DNA recognition sequence. Leucine zippers are strongly dimerized, and in a bZIP, the basic region can, in the absence of DNA, undergo extensive relative monomer-to monomer fluctuations. In this work, LZ and bZIP potentials of mean force (PMFs), which provide free energies along reaction coordinates, are simulated with a distance replica exchange method. The method uses restraint potentials to provide sampling along a reaction coordinate and enhances configuration space exploration by exchanging information between neighboring restraint potential configurations. Restraint potentials that are constructed from sums over a number of atom distances are employed. Their use requires a modification of the Weighted Histogram Analysis Method (WHAM) procedure to combine and unbias the data from the different restraint-potential-biased window densities to provide a PMF. These methods are first used to obtain a PMF for separating a leucine zipper (GCN4-p1) of the yeast transcriptional activator GCN4. The PMF indicates a very strong binding free energy that only weakens when the monomers are separated by about 12 A, which is about 6 A beyond their bound, dimer equilibrium distance. PMFs are also obtained for separating the basic subdomain monomer parts of the GCN4 bZIP transcriptional factor, in the absence of DNA. In a monomer separation range spanning the open, crystal-based structure to closer configurations, the basic subdomain PMF is quite flat, implying essentially thermal sampling in this distance range. A PMF generated starting from a "collapsed" state, taken from a previous simulation ( J. Phys. Chem. B 2012 , 116 , 6071 ), where collapsed refers to the feature that the basic subdomain monomers are also effectively dimerized, shows that this state is bound in free energy, though much less so than the leucine zipper dimer. PMID- 25124230 TI - A study on the mechanism by which MDMA protects against dopaminergic dysfunction after minimal traumatic brain injury (mTBI) in mice. AB - Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI). Experimental mTBI was induced using a concussive head trauma device. One hour before injury, animals were subjected to MDMA. Administration of MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels that were observed in mTBI mice. This normalization was also able to lower the elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived neurotrophic factor (BDNF) levels did not change following injury alone, but in mice subjected to MDMA and mTBI, significant elevations were observed. In the behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was administered prior to injury. Altered catecholamine synthesis and high D2 receptor levels contribute to cognitive dysfunction, and strategies to normalize TH signaling and D2 levels may provide relief for the deficits observed after injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing regular dopamine system activity. While the beneficial effect we observe was due to a dangerous recreational drug, understanding the alterations in dopamine and the mechanism of dysfunction at a cellular level can lead to legal therapies and potential candidates for clinical use. PMID- 25124234 TI - MOF-derived porous ZnO/ZnFe2O4/C octahedra with hollow interiors for high-rate lithium-ion batteries. AB - Novel porous ZnO/ZnFe2O4/C octahedra with hollow interiors are fabricated by a facile self-sacrificing template method involving the refluxing synthesis of hollow, metal-organic framework octahedra in solution and subsequent thermal annealing in N2 . When evaluated as an anode material for lithium-ion batteries, these porous hollow ZnO/ZnFe2O4/C octahedra exhibit significantly enhanced electrochemical performances with high rate capability, high capacity, and excellent cycling stability. PMID- 25124235 TI - The significance of circulating tumour cells in breast cancer: a review. AB - Haematogenous spread of circulating tumour cells (CTCs) is the principle mechanism for development of metastases. Research into the enumeration and characterisation of CTCs, particularly in the last decade, has allowed the introduction of semi-automated CTC assessment in the clinical setting. In breast cancer, CTC enumeration is being used as a prognostic biomarker, a predictive biomarker of treatment response and is being assessed to guide treatment in both the early and metastatic setting. CTC characterisation has the potential to direct targeted therapies, such as HER2 therapies in HER2 negative primary breast tumour patients. However, CTC assessment has considerable challenges. Capture and identification of these very rare cells is currently largely dependent on a presumed homogeneity of phenotype. In addition, high throughput assays are lacking. The clinical significance of CTCs is incompletely understood. A large proportion of CTC positive patients have no evidence of metastases, raising the issue of either inconsequential tumour dormancy or non-viable CTCs. CTCs may have additional clinical sequelae such as promoting venous thrombosis. However CTCs provide a real-time liquid biopsy of the tumour and represent an exciting, minimally invasive method of assessing disease status and also a novel therapeutic target for malignancy. PMID- 25124236 TI - The net clinical benefit of personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention. AB - This was a prospective study comparing two groups: personalized and non personalized treatment with P2Y12 receptor blockers during a 12-month follow-up. We aimed to investigate whether personalized antiplatelet treatment in patients with high on-treatment platelet reactivity (HTPR) improves clinical outcome. Platelet reactivity was assessed by adenosine diphosphate induced aggregation using a multiple electrode aggregometry (MEA) in 798 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Patients with HTPR received up to four repeated loading doses of clopidogrel or prasugrel in the personalized treatment group (n=403), whereas no change in the treatment strategy was undertaken in patients with HTPR in the non-personalized treatment group (n=395). There were fewer major adverse cardiac events (MACE) in the personalized treatment group than in the non-personalized treatment group (7.4% compared with 15.3% respectively; P<0.001). The multivariate Cox regression analysis showed that the relative risk to develop MACE was 51% lower in the personalized treatment group as compared with the non-personalized treatment group [hazard ratio (HR)=0.49; 95% confidence interval (CI): 0.31-0.77; P<0.001]. Similarly, there was a clear net benefit of the personalized antiplatelet treatment over the non-personalized treatment (ischemic and bleedings events: 8.2% versus 18.7% respectively; HR=0.46; 95%CI: 0.29-0.70; P<0.001). Further analysis indicated that patients with aggregation values within the therapeutic window (21-49 units) experienced the lowest event rates (stent thrombosis and major bleeding: 2.5%) as compared with poor responders (>=50 units: 5.4%) or ultra-responders (0-20 units: 5.2%). In conclusion, personalized antiplatelet treatment might improve patients' outcome without increasing bleeding complications compared with the non-personalized treatment during a 12-month follow-up. PMID- 25124237 TI - Impact of the quadrivalent HPV vaccine on disease recurrence in men exposed to HPV Infection: a randomized study. AB - INTRODUCTION: Human papillomavirus (HPV) is one of the most common sexually transmitted infections and is the cause of several different diseases in men and women. Although little is known about HPV infection in men, they are also in the risk group of HPV infection and play an important role in transmitting the virus to women. AIM: To define the efficacy of the HPV vaccine through cross immunization and its role in clearance of HPV infection, and to assess infection associated factors in men. METHODS: This prospective randomized clinical study enrolled 171 evaluable men with genital warts between June 2009 and October 2013. After the initial treatment intervention, 91 patients were randomly assigned to receive HPV vaccine in three doses. Eighty patients were in the control (unvaccinated) group. One hundred-eleven men were single and 60 men were married. Patients who had previous treatment for pre-existing warts and medical disorders that needed chronic treatment or immunosuppression were not included in the randomization. Also 29 men with follow-up less than 12 months and incomplete vaccination were not included. MAIN OUTCOME MEASURES: The patients were assessed regarding age, condom use, marital status, number of visible genital warts, and smoking status. Post-treatment follow-up was monthly up to 12th month. RESULTS: Mean age was 34 +/- 7.6. One hundred fifteen patients were smokers. For the recurrence of warts, age, smoking, vaccination status were insignificant and marital status was significant in the univariable analysis; only marital status preserved significance (HR: 2.0 CI:1.29-3.12 P = 0.002) in the multivariable analysis including vaccination status, marital status, and smoking. CONCLUSION: Among the investigated factors vaccination status was not but marital status significantly influenced wart recurrence. Married men had more recurrences in our population. Larger multicenter randomized clinical trials are lacking and seriously required to investigate the therapeutic effect of current quadrivalent HPV vaccine in genital warts. PMID- 25124238 TI - Pregnancy does not increase the local recurrence rate after surgical resection of desmoid-type fibromatosis. AB - BACKGROUND: Pregnancy has been reported as a risk factor for promoting growth and progression of desmoid-type fibromatosis because of the presumed role of estrogens in stimulating desmoid growth. In this study, the clinical outcomes of females who were pregnant 5 years or less before resection of desmoid tumor or who became pregnant after resection were compared to nulliparous females or females who were pregnant more than 5 years before resection. METHODS: Obstetric histories of desmoid tumor patients were abstracted from medical records. Patients were grouped by pregnancy status as either: pregnancy-associated (pregnant up to 5 years before primary desmoid tumor resection or pregnant after resection) or not pregnancy-associated (nulliparous or pregnant more than 5 years before resection of desmoid tumor). Cox proportional hazards regression was used to evaluate pregnancy status as a predictor of desmoid tumor recurrence. RESULTS: There were 15 females who had pregnancy-associated desmoids (33%) and 31 females who had non-pregnancy-associated desmoids (67%). There were no differences in clinicopathologic features or recurrence-free survival between females of different pregnancy status in univariate or multivariate survival analyses. CONCLUSION: Recurrence-free survival rates among women recently pregnant before or pregnant after resection of desmoid tumor and nulliparous women or those with a remote history of pregnancy are comparable after adjusting for patient age, anatomic location, and completeness of surgical resection. Subsequent pregnancy should not be discouraged for reproductive-aged women after resection of desmoid type fibromatosis. PMID- 25124239 TI - A combinatorial approach towards water-stable metal-organic frameworks for highly efficient carbon dioxide separation. AB - A library of 20 UiO-66-derived metal-organic frameworks (MOFs) is synthesized in a combinatorial approach involving mixed ligand copolymerization and two post synthetic modifications (PSMs) in tandem. Mixed ligand co-polymerization of benzene-1,4-dicarboxylic acid (BDC) and sodium 2-sulfoterephthalate (SS-BDC) with zirconium tetrachloride (ZrCl4 ) was used to prepare 5 groups of MOFs with the same UiO-66 topology but differing amounts of sulfate groups. These MOFs exhibit excellent water stabilities in a pH range of 1 to 12, together with high CO2 uptake capacities and selectivities. PMID- 25124240 TI - The state of epidemiological knowledge in the 21st century. PMID- 25124241 TI - [Disease transmission dynamics according to complexity theory]. AB - OBJECTIVE: Illustrating disease transmission as a complex system according to complexity theory. METHODS: A SIR mathematical model (S=number susceptible, I=number infectious, and R=number recovered or immune) reflecting disease transmission from the connection between states of susceptibility, infection, disease, recovery and nonlinearity in the interaction between susceptible and infected was simulated. Infection rate temporal fluctuations were described by logistic mapping. RESULTS: Transmission occurs with the reduction of susceptible states as people become infected and sick, followed by an increase in individuals' recovery following diagnosis and treatment. Small increases in infection rate value led to fluctuations in the number of susceptible and exposed people and randomness in the relationship between being susceptible and infected, until converging towards a regular pattern. CONCLUSION: The model reflected the connection between states of susceptibility, nonlinearity and chaotic behavior following small increases in infection rate. A historical and trans-disciplinary perspective could help in understanding transmission complexity and coordinating control options. PMID- 25124242 TI - [The contribution of epidemiology to disease control: malaria]. AB - Despite the number of cases and attributable mortality having become reduced, malaria continues to be an important public health problem. This report presents some examples of epidemiology's contribution to malaria control; it also motivates reflexion to the contrary, i.e. malaria's contribution to the development of epidemiology. Attempting to identify methods for measuring epidemiology's contribution to malaria control led to an in-depth analysis of what exactly does epidemiology consist of, whether all its contributions could be considered positive and to what extent they might have been due just to epidemiology. PMID- 25124244 TI - [The role of research-based evidence in health system policy decision-making]. AB - Different models may be used for explaining how research-based evidence is used in healthcare system policy-making. It is argued that models arising from a clinical setting (i.e. evidence-based policy-making model) could be useful regarding some types of healthcare system decision-making. However, such models are "silent" concerning the influence of political contextual factors on healthcare policy-making and are thus inconsistent with decision-making regarding the modification of healthcare system arrangements. Other political science-based models would seem to be more useful for understanding that research is just one factor affecting decision-making and that different types of research-based evidence can be used instrumentally, conceptual or strategically during different policy-making stages. PMID- 25124243 TI - [Colombian experience regarding skin cancer: healthcare-related barriers to access to healthcare and bureaucratic itineraries]. AB - OBJECTIVES: Describing and understanding the experiences of people suffering non melanoma skin cancer in their struggles to recuperate, deciphering their itinerary regarding their health-seeking behavior, describing the relationship between patients and the Colombian healthcare system by referring to the number of pertinent writs and the percentage of denied services, and documenting the determinants which are related to timely diagnosis. METHODS: This was a mixed methods study, combining epidemiology and critical medical anthropology; the study involved a retrospective cohort of 369 people, 3 focus groups including 48 participants and in-depth interviews regarding 20 cases. RESULTS: The data revealed specific healthcare system-related barriers to access to healthcare, intermediate barriers (work-related and geographical) and structural barriers (economic-, income-, purchasing power-, social cohesion- and education-related). Timely diagnosis was made in 32.5% of the reported cases. Related determinants consisted of educational level equal to or above technical training (OR 4.4), home ownership (OR 4.8), living in an urban area (OR3.5) and contributory regime affiliation (OR 1.9); 28% of the people involved in the study reported that they had been denied access to a service (biopsy, surgery) and the rate of resorting to legal means (i.e. writs) was 5 out of every 100 new cases per year. The itinerary from the time of the appearance of a particular disease to definitive resolution was established. DISCUSSION: People living in unfavorable social conditions were involved in the severest cases and, paradoxically, faced the largest set of barriers to access to healthcare in Colombia. Such barriers extend beyond the healthcare system and will not become resolved solely through healthcare reform. PMID- 25124245 TI - [Evidence-based public health decision-making tools which can also be used for prioritising disease]. AB - He use of research-based evidence has been promoted during recent years, due to the increasing development of evidence-based medicine,and it has been reported that transferring the concept of "evidence-based" from clinical to public health practice has not been as straight forward as expected.Much research-based evidence for supporting public health recommendations has come from studies whose evidence has been qualified as being low or very low quality in the medical hierarchy based on classic evidence and the grading of recommendations, assessment, development and evaluation (GRADE)approach. This paper was aimed at presenting two methods of rating evidence, as well as their limitations and applications as public health decision-making tools. PMID- 25124246 TI - [The background, development and perspectives of modern epidemiology]. AB - Epidemiology is an ongoing discipline (i.e. still being constructed) and many of the foundations of the theory and methods now in use were mostly developed during the second half of the twentieth century, arising from what is known today as "modern epidemiology". This paper summary the history and main ideas which guided epidemiology at that time, the debates and divisions that characterized such advance and presents a "biased" point of view concerning the perspectives which could help thinking about the disciplinary development of epidemiology. PMID- 25124247 TI - [A Latin-American perspective regarding the past, present and future of epidemiology]. AB - This article addresses three questions. Concerning the past, why was there no pre Columbian epidemiology? What are the origins of modern epidemiology (including its South American roots)? A surrealistic title has been chosen regarding the future to emphasise the fact that making predictions is not easy. Why are complex phenomena the dark object of epidemiological desire? PMID- 25124248 TI - [Latin-American public policy regarding social determinants of health]. AB - The study was aimed at identifying Latin-American countries' public policy which has been related to the social determinants of health. A topic review was thus made of papers kept in the 22 Latin-American countries' databases and official documents issued by their multilateral organisations and ministries of health. The World Health Organization's concept of the social determinants of health has been summarised and a history given of the pertinent work developed worldwide in regions such as Europe and Latin-America. Public policy regarding the field of study in Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Mexico and Venezuela has been described. It was concluded that Latin-America provides a panorama of inequality regarding the application of policy concerning the social determinants of health and that there was segmented intervention, mainly regarding intermediate determinants of health, without taking an integrated approach from different entrance points into account, according to the stated conceptual framework. PMID- 25124249 TI - [Ascertaining a Venezuelan oil town's health conditions]. AB - Objective Analysing health conditions in the town of Carirubana in Falcon State, Venezuela, as a prior study to the construction of a gas conditioning plant there. Methods This study formed part of a field research project which involved consulting primary and secondary sources. The former consisted of evaluating public and private health-centres and those in the Barrio Adentro system; the aforementioned health centres' medical staff were interviewed to determine current health-disease status and the factors determining health for the town being studied. Likewise, both situations (health-disease and factors determining health) were evaluated and analysed in the secondary sources at national, state and municipal level. Results Deficits were observed at national level regarding public health infrastructure; there were 1.3 beds per thousand inhabitants, this being less than half that recommended by the World Health Organization (WHO) (i.e. three to four beds per thousand inhabitants). State and municipal cancer mortality rates were relatively stable over a four-year period (2001-2004). Conclusions The mortality rate in Carirubana was characteristic of a low-income area. The poverty and pollution directly produced by the oil refining plants were the key determinants for this town's morbidity and mortality rates. PMID- 25124251 TI - [An occupational evaluation of disabled people from a human abilities' viewpoint]. AB - OBJECTIVE: Describing how a tool was designed for assessing disabled people in Colombia (called "Occupational evaluation of handicapped people in Colombia"). METHOD: This was a multi-method study which consisted of five phases and a stakeholder participation-based strategy. The first stage of the multi-method research involved a literature review followed by expert judgment and then peer assessment of the tool; the fourth stage involved a pilot study and and a basic training course in occupational assessment involved the tool's socialisation with actors working in the field of occupational assessment, taking their suggestions into account for final adjustment of the tool. RESULTS: A tool was developed for the occupational assessment of disabled people in Colombia which was based on identifying their capabilities in terms of performance and general work skills to promote their inclusion in the workforce. CONCLUSIONS: Considering the Colombian state's responsibility for ensuring disabled people's right to work and their inclusion in the workforce (Law 1346/2009, Law 1618/2013 and Convention on the Rights of People with Disabilities (CRPD)), this tool will not replace existing ones but will promote a more favourable perception of disabled people, thereby facilitating their inclusion in the workforce. PMID- 25124250 TI - [A study concerning how much weight schoolchildren carry in their bags, involving four schools in the metropolitan area of Buenos Aires, Argentina]. AB - OBJECTIVE: Determining the weight children carry in their bags to school (absolute and relative values) and the distance walked during home-school routes, involving students from four schools in the metropolitan area of Buenos Aires. METHOD: The study involved 751 primary (4th to 6th grades) and secondary (1st to 3rd years) level students who were attending three private schools and one public one. Body and bag weights were measured and the children were asked about the distance (in blocks) they walked from school to home. The study involved a descriptive analysis and contrasted the students by gender, educational level, type of school and grade or year. Possible associations between variables were ascertained. The group was divided into those carrying bags weighing less than 10% of their body weight and those who carrying 10% (considered a critical value) and more; frequencies were calculated by the type of bag being used. RESULTS: 68% of the sample were carrying 10% or more of their body weight (P42=10.13%): 66% in male (P44=10.12%) and 60% in female children (P40=10.2%). Private school students carried more weight than public school children (p<0.05) and younger students carried a greater weight than older students (p<0.05) in both educational levels. CONCLUSIONS: Most children were carrying relative weights well above that recommended and female students were most affected. Younger students carried higher absolute and relative weights. PMID- 25124252 TI - [The characterization of biosolids produced by the San Fernando wastewater treatment plant in Itagui, Antioquia, Colombia]. AB - ABSTRACT Objective This study was aimed at evaluating pertinent physicochemical and microbiological (bacteria and parasites) parameters regarding the biosolids produced by the San Fernando wastewater treatment plant (WWTP) in Itagui, Antioquia, Colombia. Methods Twelve samples were collected and evaluated every month from January to December during 2010. The chemical, physical and microbiological tests followed the protocol described in Colombian technical guideline 5167. The protocol described in Mexican official Norm 004 (with some modifications) was used for identifying helminth ova and assessing their viability. Results All samples proved positive for Ascarislumbricoides, viable ova count ranging from 4 to 22 eggs/2gTS. Both Salmonella and Enterobacteriawere detected in all samples evaluated, the latter having 3,000 colony forming unit (CFU)/g minimum concentration. Biosolid sample values met the heavy metal concentration requirement established by national guidelines. There was no statistical association between rainfall and the pathogen's presence in the biosolids. Conclusion Our results suggested that the biosolids being produced by the San Fernando wastewater treatment plant (WWTP) could be used as organic fertilizer; however they should be treated/sanitized to meet the stipulations in Colombian technical guideline 5167. PMID- 25124253 TI - Comparison of pre- and post-operative health-related quality of life and length of stay after primary total hip replacement in matched English and German patient cohorts. AB - PURPOSE: We compare pre- and post-operative health-related quality of life (HRQoL) and length of stay after total hip replacement (THR) in matched German and English patient cohorts to test for differences in admission thresholds, clinical effectiveness and resource utilisation between the healthcare systems. METHODS: German data (n = 271) were collected in a large orthopaedic hospital in Munich, Germany; English data (n = 26,254) were collected as part of the national patient-reported outcome measures programme. HRQoL was measured using the EuroQoL 5D instrument. Propensity score matching was used to construct two patient cohorts that are comparable in terms of preoperative patient characteristics. RESULTS: Before matching, patients in England showed lower preoperative EQ-5D scores (0.35 vs 0.52, p < 0.001) and experienced a larger improvement in HRQoL (0.43 vs 0.33, p < 0.001) than German patients. Patients in the German cohort were more likely to report no or only moderate problems with mobility and pain preoperatively than their English counterparts. After matching, improvements in HRQoL were comparable (0.32 vs 0.33, p = 0.638); post-operative scores were slightly higher in the German cohort (0.82 vs 0.85, p = 0.585). Length of stay was substantially lower in England than in Germany (4.5 vs 9.0 days, p < 0.001). CONCLUSIONS: Our results highlight differences in preoperative health status between countries, which may arise due to different admission thresholds and access to surgery. In terms of quality of life, THR surgery is equally effective in both countries when performed on similar patients, but hospital stay is shorter in England. PMID- 25124256 TI - Preparation of thermally stable microcapsules with a chitosan-silica hybrid. AB - Addition of microcapsules with a high dielectric constant and low specific heat capacity to a battered layer was designed to create a higher temperature in the crust than in the prefried fish nuggets to prevent the water vapor in the fish nuggets from migrating to the crust during microwave heating. Therefore, chitosan silica hybrids and soybean oil were utilized to prepare the shell and core of the thermally stable microcapsules (MC(CS)), respectively. The MC(CS) were prepared by sol-gel coacervation from an oil-in-water emulsion. The sodium silicate was hydrolyzed and coacervated through polymerization for 24 h at pH 5. The zeta potential analysis indicated that chitosan with a positive charge and silica with a negative charge interacted through electrostatic attraction to form a hybrid shell. The volume mean particle size and encapsulation efficiency of the MC(CS) were 9.6 +/- 0.2 MUm and 75.6% +/- 1.3%, respectively, when oil/chitosan = 0.2 and chitosan/silica = 0.5 (w/w). In addition to H-bonding and electrostatic attraction, Si-O-N bonds were formed between chitosan and silica. Dehydration of the bound water in the MC(CS) was observed in the range of 25 to 250 degrees C in the differential scanning calorimetry thermal analysis, with the lack of apparent thermal peaks indicating its high thermal stability. The decrease of force to cut the crust observed by texture analysis as well as the increase of hedonic score by consumer acceptance test revealed the addition of 1% MC(CS) significantly improved the crispness of the crust in the microwave-reheated nuggets. PMID- 25124254 TI - Arginase activity in alternatively activated macrophages protects PI3Kp110delta deficient mice from dextran sodium sulfate induced intestinal inflammation. AB - Alternatively activated or M2 macrophages have been reported to protect mice from intestinal inflammation, but the mechanism of protection has not been elucidated. In this study, we demonstrate that mice deficient in the p110delta catalytic subunit activity of class I phosphatidylinositol 3-kinase (PI3Kp110delta) have increased clinical disease activity and histological damage during dextran sodium sulfate (DSS) induced colitis. Increased disease severity in PI3Kp110delta deficient mice is dependent on professional phagocytes and correlates with reduced numbers of arginase I+ M2 macrophages in the colon and increased production of inflammatory nitric oxide. We further demonstrate that PI3Kp110delta-deficient macrophages are defective in their ability to induce arginase I when skewed to an M2 phenotype with IL-4. Importantly, adoptive transfer of IL-4-treated macrophages derived from WT mice, but not those from PI3Kp110delta-deficient mice, protects mice during DSS-induced colitis. Moreover, M2 macrophages mediated protection is lost when mice are cotreated with inhibitors that block arginase activity or during adoptive transfer of arginase I deficient M2 macrophages. Taken together, our data demonstrate that arginase I activity is required for M2 macrophages mediated protection during DSS-induced colitis in PI3Kp110delta-deficient mice. PMID- 25124255 TI - Rare benign tumours of the nipple. AB - BACKGROUND: Benign lesions of the breast in total are much more frequent than malignant ones. However, there are no epidemiologic data on the prevalence of benign or malignant tumours of the nipple, and the bibliography on benign nipple tumours in general is limited. AIMS: To present some rare cases of benign nipple tumours and review the literature. MATERIALS AND METHODS: Four cases of rare benign nipple tumours: neurofibromas, wart, leiomyoma and milium are presented. The literature search on benign nipple tumours was performed using MEDLINE, Pubmed, and Cochrane databases with limits: English language, human species and available abstract. The keyword used was 'benign nipple tumours'. RESULTS: The initial search retrieved 337 articles. The papers were reviewed and the articles that referred to benign lesions that appeared at the nipple specifically were identified. Different entities that were described included: neurofibroma, leiomyoma, milium, florid papillomatosis, syringomatous adenoma, nevoid hyperkeratosis, fibroma, pseudolymphoma and haemangioma. DISCUSSION: Differential diagnosis of benign tumours of the nipple can be demanding for the physicians. Many of the symptoms and signs like pruritus, serosanguinous discharge, lichenification, erosion and nodular enlargement are produced by either malignant or benign nipple lesions. Radiology can be unclear in the diagnosis of nipple abnormalities. CONCLUSION: Histological examination of the lesion can be the only definite answer in these cases. PMID- 25124257 TI - A therapeutic workplace for the long-term treatment of drug addiction and unemployment: eight-year outcomes of a social business intervention. AB - This study evaluated the long-term effects of a therapeutic workplace social business on drug abstinence and employment. Pregnant and postpartum women (N = 40) enrolled in methadone treatment were randomly assigned to a therapeutic workplace or usual care control group. Therapeutic workplace participants could work weekdays in training and then as employees of a social business, but were required to provide drug-free urine samples to work and maintain maximum pay. Three-year outcomes were reported previously. This paper reports 4- to 8-year outcomes. During year 4 when the business was open, therapeutic workplace participants provided significantly more cocaine- and opiate-negative urine samples than controls; reported more days employed, higher employment income, and less money spent on drugs. During the 3 years after the business closed, therapeutic workplace participants only reported higher income than controls. A therapeutic workplace social business can maintain long-term abstinence and employment, but additional intervention may be required to sustain effects. PMID- 25124258 TI - Injection and sexual HIV/HCV risk behaviors associated with nonmedical use of prescription opioids among young adults in New York City. AB - Prevalence of nonmedical prescription opioid (PO) use has increased markedly in the U.S. This qualitative study explores the drug-use and sexual experiences of nonmedical PO users as they relate to risk for HIV and HCV transmission. Forty six New York City young adult nonmedical PO users (ages 18-32) completed in depth, semi-structured interviews. Despite initial perceptions of POs as less addictive and safer than illegal drugs, PO misuse often led to long-term opioid dependence and transition to heroin use and drug injection. Injectors in the sample reported sporadic syringe-sharing, frequent sharing of non-syringe injection paraphernalia and selective sharing with fellow injectors who are presumed "clean" (uninfected). Participants reported little knowledge of HCV injection-related risks and safer injection practices. They also reported engaging in unprotected sex with casual partners, exchange sex and group sex, and that PO misuse increases the risk of sexual violence. Prevention efforts addressing HIV/HCV risk should be targeted to young nonmedical PO users. PMID- 25124260 TI - The clustering of psychopathology among adults seeking treatment for alcohol and drug addiction. AB - Beyond the high prevalence of co-occurring mental and substance use disorders, little is known about more complex patterns of psychopathology and multimorbidity, particularly in treatment populations. We sought to identify a parsimonious set of latent classes to describe the structure of mental disorder comorbidity among adults entering outpatient addiction treatment, and explore differences in the structure and prevalence of classes across sociodemographic characteristics. Participants (N=544) completed the Psychiatric Diagnostic Screening Questionnaire at treatment admission. We used latent class analysis to identify classes of clients with specific patterns of co-occurring mental disorders. The best-fitting solution identified 3 classes, characterized by no comorbidity (i.e., substance use disorders only), co-occurring major depression, and multimorbidity or a high degree of psychopathology. Older age was associated with lower probability of being in the class with co-occurring major depression, women were more likely than men to be in the multimorbid class, and being married or partnered was associated with a lower probability of being in either of the comorbid classes. These results are consistent with general population research on the patterning of psychiatric disorders, implying that while clients in addiction treatment may have extraordinarily high levels of psychopathology, the patterns of symptoms and the groups most affected are not markedly different than in other settings. By capturing the complexity of interrelationships among the many factors that are known to influence prognosis and outcomes, latent class analysis offers a useful way to examine and represent case-mix in clinical populations. PMID- 25124262 TI - Comment on: "Current status and trends in performance-based risk-sharing arrangements between healthcare payers and medical product manufacturers". PMID- 25124259 TI - Do improvements in substance use and mental health symptoms during treatment translate to long-term outcomes in the opposite domain? AB - Providers who treat adolescents with co-occurring substance use and mental health issues may prioritize treatment of one set of symptoms believing that improvements in one domain will result in improvements of the other. However, limited empirical data for adolescents provide evidence of such "spillover effects." Using data from 2900 youth in an outpatient treatment, we examined whether during-treatment changes in substance use or mental health symptoms predicted 12-month outcomes in the analogous and opposite domains. There was very little evidence of spillover effects, only that youth with no internal distress at 0 and 3 months reported lower levels of substance use problems at 12-months relative to youth with internal distress that stayed the same from 0 to 3 months. These findings suggest that providers treat both sets of substance use and mental health symptoms in an integrated manner given that these symptoms commonly co occur among youth with either set. PMID- 25124261 TI - The influence of treatment attendance on subsequent aggression among severely mentally ill substance abusers. AB - The interrelationships between severe mental illness, substance use, and aggression are of longstanding importance with implications for community treatment programs, treatment research and public policy. Through the analysis of longitudinal data collected from 278 patients over a 6-month period following admission to an outpatient dual diagnosis treatment program, this study examined the association between dual diagnosis treatment attendance and subsequent aggression among individuals diagnosed with both a severe mental illness and a substance use disorder. We also tested substance use and psychiatric symptoms as mediators of this treatment-aggression relationship. The results of structural equation modeling analyses indicated that dual diagnosis treatment was associated with lower levels of subsequent aggression. Mediational analyses indicated that greater treatment involvement was associated with reduced substance use, which was associated with lower levels of aggression; thus, substance use was found to mediate the relationship between dual diagnosis treatment and aggression. Surprisingly, severity of psychiatric symptoms did not predict later aggression. These findings suggest that targeting substance use reduction in treatment may have the additional benefit of reducing the risk of later aggression among dual diagnosis patients. PMID- 25124263 TI - Authors' reply to Curto and Garattini: "Current status and trends in performance based risk-sharing arrangements between healthcare payers and medical product manufacturers". PMID- 25124264 TI - Clinical outcomes in cytomegalovirus-positive Posner-Schlossman syndrome patients treated with topical ganciclovir therapy. AB - PURPOSE: To evaluate the clinical characteristics and therapeutic outcomes of cytomegalovirus (CMV)-positive Posner-Schlossman syndrome patients undergoing topical ganciclovir treatment. DESIGN: Retrospective, comparative, and interventional case series. METHODS: One eye of each of 126 consecutive Posner Schlossman syndrome patients was investigated using aqueous polymerase chain reaction (PCR) between January 2006 and June 2013. The initial presentations and follow-up data of the CMV-positive patients (68 eyes) and CMV-negative patients (58 eyes) were compared. RESULTS: Severe endothelial cell loss (P < .001) and a higher number of eyes requiring glaucoma filtering surgery (P = .017) were observed in CMV-positive Posner-Schlossman syndrome patients. All CMV-infected eyes treated with continual topical 2% ganciclovir exhibited an undetectable CMV level at the following taps. During follow-up, the average number of antiglaucomatous agents decreased, and a similar frequency of intraocular pressure (IOP) spikes was observed in both groups (P = .358). Patients with CMV positive eyes with a disease duration over 5 years were likely to require glaucoma surgery (P = .024, log-rank test). All patients receiving surgery exhibited CMV-negative PCR during the IOP attack, but experienced severe peripheral anterior synechiae and pigment clogging. Both groups exhibited a similar endothelial cell decrease (P = .243) and probability of progressive endothelial cell loss (P = .219, log-rank test). CONCLUSION: Ganciclovir treatment was effective for clearing the viral load, assisting the IOP control, and preserving the corneal endothelium of CMV-positive Posner-Schlossman syndrome patients. Early diagnosis and proper treatment could decrease the risk of advanced glaucoma and avoid glaucoma surgery in long-lasting cases. PMID- 25124265 TI - Dome-shaped macular configuration: longitudinal changes in the sclera and choroid by swept-source optical coherence tomography over two years. AB - PURPOSE: To study longitudinal changes in the posterior pole in eyes with dome shaped macular configuration within the staphyloma. DESIGN: Prospective, longitudinal study. METHODS: We prospectively examined the macular area in 35 eyes (26 patients) with dome-shaped macular configuration and high myopia (mean spherical equivalent, -14.83 +/- 4.50 diopters) using swept-source optical coherence tomography. Scleral and choroidal thicknesses were measured at the fovea and at 4 parafoveal locations 2000 MUm from the foveal center. Height of the macular bulge was measured as well. RESULTS: During the mean follow-up of 24.8 +/- 2.5 months, the scleral thickness significantly decreased at the fovea from 496.1 +/- 95.7 MUm to 484.7 +/- 96.2 MUm (P < .001) and at all 4 parafoveal locations (P < .001, respectively). The scleral thinning was asymmetric, with an estimated decrease per year of 5.6 MUm at the foveal center, 11.1 MUm superiorly, 12.1 MUm inferiorly, 10.4 MUm temporally, and 5.8 MUm nasally. The ocular concavities deepened over time, and mean macular bulge height increased from 136.5 +/- 60.9 MUm to 157.6 +/- 67.0 MUm (P < .001). The choroid within the staphyloma showed generalized thinning during follow-up. Mean choroidal thickness decreased significantly at the fovea from 28.3 +/- 17.2 MUm at baseline to 22.9 +/- 17.2 MUm (P < .001). CONCLUSIONS: Progressive asymmetric scleral thinning occurred in the macular region of eyes with dome-shaped macular configuration. The scleral thinning was more pronounced in the parafoveal area than at the foveal center, resulting in an increase of the macular bulge height. PMID- 25124266 TI - [Annular pancreas: a potentially overlooked congenital pancreatic anomaly]. PMID- 25124267 TI - South Africans with recent pregnancy rarely know partner's HIV serostatus: implications for serodiscordant couples interventions. AB - BACKGROUND: Implementation of safer conception strategies requires knowledge of partner HIV-serostatus. We recruited women and men in a high HIV-prevalence setting for a study to assess periconception risk behavior among individuals reporting HIV-serodiscordant partnerships. We report screening data from that study with the objective of estimating the proportion of individuals who are aware that they are in an HIV-serodiscordant relationship at the time of conception. METHODS: We screened women and men attending antenatal and antiretroviral clinics in Durban, South Africa for enrollment in a study of periconception risk behavior among individuals with serodiscordant partners. Screening questionnaires assessed for study eligibility including age 18-45 years (for women) or at least 18 years of age (for men), pregnancy in past year (women) or partner pregnancy in the past 3 years (men), HIV status of partner for recent pregnancy, participant's HIV status, and infected partner's HIV status having been known before the referent pregnancy. RESULTS: Among 2620 women screened, 2344 (90%) met age and pregnancy criteria and knew who fathered the referent pregnancy. Among those women, 963 (41%) did not know the pregnancy partner's HIV serostatus at time of screening. Only 92 (4%) reported knowing of a serodiscordant partnership prior to pregnancy. Among 1166 men screened, 225 (19%) met age and pregnancy criteria. Among those men, 71 (32%) did not know the pregnancy partner's HIV status and only 30 (13%) reported knowing of a serodiscordant partnership prior to pregnancy. CONCLUSIONS: In an HIV-endemic setting, awareness of partner HIV serostatus is rare. Innovative strategies to increase HIV testing and disclosure are required to facilitate HIV prevention interventions for serodiscordant couples. PMID- 25124268 TI - Cardiovascular changes after administration of aerosolized salbutamol in horses: five cases. AB - Prevention and treatment of intraoperative hypoxemia in horses is difficult and both efficacy and safety of therapeutic maneuvers have to be taken into account. Inhaled salbutamol has been suggested as treatment of hypoxia in horses during general anesthesia, due to safety and ease of the technique. The present report describes the occurrence of clinically relevant unwanted cardiovascular effects (i.e. tachycardia and blood pressure modifications) in 5 horses undergoing general anesthesia in dorsal recumbency after salbutamol inhalation. Balanced anesthesia based on inhalation of isoflurane in oxygen or oxygen and air and continuous rate infusion (CRI) of lidocaine, romifidine, or combination of lidocaine and guaifenesine and ketamine was provided. Supportive measures were necessary to restore normal cardiovascular function in all horses but no long term adverse effects were noticed in any of the cases. PMID- 25124269 TI - Organic aerosols and inorganic species from post-harvest agricultural-waste burning emissions over northern India: impact on mass absorption efficiency of elemental carbon. AB - Atmospheric PM2.5 (particulate matter with aerodynamic diameter of <= 2.5 MUm), collected from a source region [Patiala: 30.2 degrees N; 76.3 degrees E; 250 m above mean sea level] of emissions from post-harvest agricultural-waste (paddy residue) burning in the Indo-Gangetic Plain (IGP), North India, has been studied for its chemical composition and impact on regional atmospheric radiative forcing. On average, organic aerosol mass accounts for 63% of PM2.5, whereas the contribution of elemental carbon (EC) is ~3.5%. Sulphate, nitrate and ammonium contribute up to ~85% of the total water-soluble inorganic species (WSIS), which constitutes ~23% of PM2.5. The potassium-to-organic carbon ratio from paddy residue burning emissions (KBB(+)/OC: 0.05 +/- 0.01) is quite similar to that reported from Amazonian and Savanna forest-fires; whereas non-sea-salt-sulphate to-OC ratio (nss-SO4(2-)/OC: 0.21) and nss-SO4(2-)/EC ratio of 2.6 are significantly higher (by factor of 5 to 8). The mass absorption efficiency of EC (3.8 +/- 1.3 m(2) g(-1)) shows significant decrease with a parallel increase in the concentrations of organic aerosols and scattering species (sulphate and nitrate). A cross plot of OC/EC and nss-SO4(2-)/EC ratios show distinct differences for post-harvest burning emissions from paddy-residue as compared to those from fossil-fuel combustion sources in south-east Asia. PMID- 25124270 TI - Comparison of phloem and xylem hydraulic architecture in Picea abies stems. AB - The hydraulic properties of xylem and phloem differ but the magnitude and functional consequences of the differences are not well understood. Phloem and xylem functional areas, hydraulic conduit diameters and conduit frequency along the stems of Picea abies trees were measured and expressed as allometric functions of stem diameter and distance from stem apex. Conductivities of phloem and xylem were estimated from these scaling relations. Compared with xylem, phloem conduits were smaller and occupied a slightly larger fraction of conducting tissue area. Ten times more xylem than phloem was annually produced along the stem. Scaling of the conduit diameters and cross-sectional areas with stem diameter were very similar in phloem and xylem. Phloem and xylem conduits scaled also similarly with distance from stem apex; widening downwards from the tree top, and reaching a plateau near the base of the living crown. Phloem conductivity was estimated to scale similarly to the conductivity of the outermost xylem ring, with the ratio of phloem to xylem conductivity being c. 2%. However, xylem conductivity was estimated to increase more than phloem conductivity with increasing tree dimensions as a result of accumulation of xylem sapwood. Phloem partly compensated for its smaller conducting area and narrower conduits by having a slightly higher conduit frequency. PMID- 25124271 TI - Effects of two different anesthetic protocols on cardiac flow measured by two dimensional phase contrast magnetic resonance imaging. AB - Companion animals are routinely anesthetized or heavily sedated for cardiac MRI studies, however effects of varying anesthetic protocols on cardiac function measurements are incompletely understood. The purpose of this prospective study was to compare effects of two anesthetic protocols (Protocol A: Midazolam, fentanyl; Protocol B: Dexmedetomidine) on quantitative and qualitative blood flow values measured through the aortic, pulmonic, mitral, and tricuspid valves using two-dimensional phase contrast magnetic resonance imaging (2D PC MRI) in healthy dogs. Mean flow per heartbeat values through the pulmonary artery (Qp) and aorta (Qs) were compared to right and left ventricular stroke volumes (RVSV, LVSV) measured using a reference standard of 2D Cine balanced steady-state free precession MRI. Pulmonary to systemic flow ratio (Qp/Qs) was also calculated. Differences in flow and Qp/Qs values generated using 2D PC MRI did not differ between the two anesthetic protocols (P = 1). Mean differences between Qp and RVSV were 3.82 ml/beat (95% limits of agreement: 3.62, -11.26) and 1.9 ml/beat ( 7.86, 11.66) for anesthesia protocols A and B, respectively. Mean differences between Qs and LVSV were 1.65 ml/beat (-5.04, 8.34) and 0.03 ml/beat (-4.65, 4.72) for anesthesia protocols A and B, respectively. Mild tricuspid or mitral reflux was seen in 2/10 dogs using 2D PC MRI. No aortic or pulmonic insufficiency was observed. Findings from the current study indicated that these two anesthetic protocols yield similar functional measures of cardiac blood flow using 2D PC MRI in healthy dogs. Future studies in clinically affected patients are needed. PMID- 25124272 TI - Closed-globe injuries of the ocular surface associated with combat blast exposure. AB - PURPOSE: To describe closed-globe conjunctival and corneal injuries and endothelial cell abnormalities associated with blast exposure and their relationships to other closed-globe injuries and blast-event characteristics. DESIGN: Observational cross-sectional study. PARTICIPANTS: Veterans with a history of blast-related traumatic brain injury (TBI). METHODS: History and ocular examination, including slit-lamp biomicroscopy, gonioscopy, specular microscopy. MAIN OUTCOME MEASURES: Type and location of blast injuries to the conjunctiva and cornea. RESULTS: Ocular surface injuries were present in 25% (16 of 65) of blast-exposed veterans with TBI. Injuries included partial-thickness anterior stromal corneal scars (15 eyes), Descemet membrane ruptures (6 eyes), and conjunctival or corneal foreign bodies (7 eyes). Based on normative information from an age-matched comparison group, endothelial cell abnormalities were identified in 37% of participants. Eyes with ocular surface injury were more likely to have lower endothelial cell density, higher coefficient of variation of cell area, and lower percentage of hexagonal cells compared with eyes without injury. Presence of ocular surface injury or endothelial cell abnormalities was associated with elevated rates of other anterior and posterior segment injuries, as well as impairment of visual acuity. We found no relationship between ballistic eyewear use or severity level of TBI and presence of ocular surface injuries from blast. CONCLUSIONS: Independent of TBI severity or use of protective eyewear, ocular surface injuries and endothelial cell abnormalities were found in significant numbers of veterans with blast-related brain injury. Descemet membrane ruptures from blast exposure were described. Ocular surface trauma was associated with other ocular injuries throughout the globe. Potential mechanisms for the types and locations of ocular injuries seen were discussed. Any corneal or conjunctival injury in a blast survivor should prompt a thorough ocular trauma examination, including gonioscopy and specular microscopy, with appropriate follow-up for associated injuries. Longitudinal studies are required to determine long-term visual outcomes after blast exposure. PMID- 25124274 TI - Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats. AB - Deep brain stimulation (DBS) is effective in managing motor symptoms of Parkinson's disease in well-selected individuals. Recently, research has shown that DBS in the basal ganglia (BG) can alter neural circuits beyond the traditional basal ganglia-thalamus-cortical (BG-TH-CX) loop. For instance, functional imaging showed alterations in cerebellar activity with DBS in the subthalamic nucleus (STN). However, these imaging studies revealed very little about how cell-specific cerebellar activity responds to STN stimulation or if these changes contribute to its efficacy. In this study, we assess whether STN DBS provides efficacy in managing motor symptoms in Parkinson's disease by recruiting cerebellar activity. We do this by applying STN-DBS in hemiparkinsonian rats and simultaneously recording neuronal activity from the STN, brainstem and cerebellum. We found that STN neurons decreased spiking activity by 55% during DBS (P = 0.038), which coincided with a decrease in most pedunculopontine tegmental nucleus and Purkinje neurons by 29% (P < 0.001) and 28% (P = 0.003), respectively. In contrast, spike activity in the deep cerebellar nuclei increased 45% during DBS (P < 0.001), which was likely from reduced afferent activity of Purkinje cells. Then, we applied STN-DBS at sub-therapeutic current along with stimulation of the deep cerebellar nuclei and found similar improvement in forelimb akinesia as with therapeutic STN-DBS alone. This suggests that STN-DBS can engage cerebellar activity to improve parkinsonian motor symptoms. Our study is the first to describe how STN-DBS in Parkinson's disease alters cerebellar activity using electrophysiology in vivo and reveal a potential for stimulating the cerebellum to potentiate deep brain stimulation of the subthalamic nucleus. PMID- 25124275 TI - A web-based platform to support an evidence-based mental health intervention: lessons from the CBITS web site. AB - OBJECTIVE: To explore the role of Web-based platforms in behavioral health, the study examined usage of a Web site for supporting training and implementation of an evidence-based intervention. METHODS: Using data from an online registration survey and Google Analytics, the investigators examined user characteristics and Web site utilization. RESULTS: Site engagement was substantial across user groups. Visit duration differed by registrants' characteristics. Less experienced clinicians spent more time on the Web site. The training section accounted for most page views across user groups. Individuals previously trained in the Cognitive-Behavioral Intervention for Trauma in Schools intervention viewed more implementation assistance and online community pages than did other user groups. CONCLUSIONS: Web-based platforms have the potential to support training and implementation of evidence-based interventions for clinicians of varying levels of experience and may facilitate more rapid dissemination. Web-based platforms may be promising for trauma-related interventions, because training and implementation support should be readily available after a traumatic event. PMID- 25124273 TI - Metabolism in HD: still a relevant mechanism? AB - The polyglutamine expansion within huntingtin is the causative factor in the pathogenesis of Huntington's disease (HD). Although the underlying mechanisms by which mutant huntingtin causes neuronal dysfunction and degeneration have not been fully elucidated, compelling evidence suggests that mitochondrial dysfunction and compromised energy metabolism are key players in HD pathogenesis. Longitudinal studies of HD subjects have shown reductions in glucose utilization before the disease clinical onset. Preferential striatal neurodegeneration, a hallmark of HD pathogenesis, also has been associated with interrupted energy metabolism. Data from genetic HD models indicate that mutant huntingtin disrupts mitochondrial bioenergetics and prevents adenosine triphosphate (ATP) generation, implying altered energy metabolism as an important component of HD pathogenesis. Here we revisit the evidence of abnormal energy metabolism in the central nervous system of HD patients, review our current understanding of the molecular mechanisms underlying abnormal metabolism induced by mutant huntingtin, and discuss the promising therapeutic development by halting abnormal metabolism in HD. PMID- 25124277 TI - Quantification of polyphenols and evaluation of antimicrobial, analgesic and anti inflammatory activities of aqueous and acetone-water extracts of Libidibia ferrea, Parapiptadenia rigida and Psidium guajava. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Vast numbers of plant species from northeastern Brazil have not yet been phytochemically or biologically evaluated. AIM OF THE STUDY: The goal of this work was to obtain, characterize and show the antimicrobial, analgesic and anti-inflammatory activities of aqueous and acetone water extracts of Libidibia ferrea, Parapiptadenia rigida and Psidium guajava. MATERIALS AND METHODS: The plant material (100g) was dried, and the crude extracts were obtained by using turbo-extraction (10%; w/v) with water or acetone:water (7:3, v/v) as the extraction solvent. High-performance liquid chromatography (HPLC) methods were used to screen the crude extracts for hydrolysable tannins (gallic acid) and condensed tannins (catechins). The antibacterial activity was evaluated by agar-diffusion and microdilution methods against Gram-positive strains (Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis INCQS 00016, Enterococcus faecalis ATCC 29212 and a clinical isolate of methicillin-resistant Staphylococcus aureus) as well as Gram-negative strains (Escherichia coli ATCC 25922, Salmonella enteritidis INCQS 00258, Shigella flexneri and Klebsiella pneumoniae). To evaluate the anti-inflammatory activity, a leukocyte migration model was used. Analgesic activity was determined by the hot plate test and the acetic acid-induced abdominal writhing test. Data were analyzed by analysis of variance (ANOVA) at a significance level of 5%. RESULTS: Parapiptadenia rigida presented the highest amount of total polyphenols (35.82 +/ 0.20%), while the greatest catechin content was found in the acetone-water extract of Psidium guajava (EAWPg; 1.04 MUg/g). The largest amounts of catechins were found in the aqueous extract of Libidibia ferrea (EALf; 1.07 MUg/g) and the acetone-water extract of Parapiptadenia rigida (EAWPr; 1.0 MUg/g). All extracts showed activity against Gram-positive bacteria. The aqueous and acetone-water extracts of Psidium guajava showed the greatest inhibition zones in the agar diffusion tests. In the evaluation of the minimum inhibitory concentration (MIC), the most susceptible Gram-positive bacterium was Staphylococcus epidermidis and the most susceptible Gram-negative bacterium was Shigella flexneri. EAPg and EAWPg showed the greatest MIC values. All extracts were significant inhibitors of leukocyte migration (p<0.05). Using the writhing test, significant analgesic activity was found for EAPr (50 mg/kg), EAWPr (100 mg/kg and 200 mg/kg) and EAWPg (50 mg/kg) (p<0.05). CONCLUSIONS: Thus, the appropriate extraction procedure preserves the chemical components such as gallic acid and catechin, and showed antimicrobial, anti-inflammatory and analgesic properties. PMID- 25124276 TI - Attenuation of inflammatory mediators, oxidative stress and toxic risk evaluation of Aporosa lindleyana Baill bark extract. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, Aporosa lindleyana Baill. has been used against various ailments viz. jaundice, fever, headache, seminal loss and insanity. The present study aims to evaluate the anti-inflammatory and anti oxidant activity of the ethanolic extract of Aporosa lindleyana Baill. bark and its fractions. METHOD: The anti-inflammatory activity of ethanolic extract of Aporosa lindleyana Baill. bark and its various fractions at doses of 200mg/kg and 300mg/kg b.w. has been carried out by a carrageenan induced hind paw edema method. To establish the probable mechanism of action, TNF-alpha and NO levels have been estimated by an ELISA method and the effect of active fraction on COX-2 and NF-kappaB expressions has been evaluated. The effect on the levels of anti oxidative enzymes (CAT, SOD & GPX) by the ethanolic extract and its fractions has also been investigated. Furthermore, peptic ulcer and hepatotoxic risk evaluation has also been carried out at three times higher dose than that used in inflammatory in vivo model. RESULTS: Among the extract and its various fractions tested for anti-inflammatory activity, the methanolic fraction at a dose of 300mg/kg showed significant inhibition in paw edema by 73% as compared to Indomethacin which showed 77% inhibition after 5h. The same dose of methanolic fraction also caused significant reduction in TNF-alpha (59.27%) and NO concentration (57.12%) while Indomethacin showed inhibition of 63.91% and 60.12%. The active methanolic fraction was also found to inhibit the expression of NF kappaB and COX-2 induced by carrageenan. Histological studies showed that the ethanolic extract and its fractions did not cause any damage to the stomach as well as to liver. Moreover, the active fractions also decreased lipid peroxidation levels and increased the antioxidant enzyme activities (SOD, CAT, GPX). CONCLUSION: The results of present study demonstrated that significant anti inflammatory activity of methanolic fraction of Aporosa lindleyana may be attributed to the modulation of pro-inflammatory mediators. Same fraction was also found to be effective against oxidative stress as it was found to elevate the levels of anti-oxidative enzymes. It can therefore be concluded that the methanolic fraction could be explored as a disease modifying agent against inflammation and oxidative stress. PMID- 25124278 TI - Expression of the vascular endothelial growth factor receptor system in porcine oviducts after induction of ovulation and superovulation. AB - This study was performed to determine the influence of insemination as well as treatment with human chorionic gonadotropin (hCG) and equine chorionic gonadotropin (eCG) on expression of the vascular endothelial growth factor (VEGF) system in porcine oviducts. In the first experiment, 10 gilts were assigned to 2 groups: cyclic (treated with phosphate-buffered saline; n = 5) and inseminated (n = 5). In experiment II, 15 gilts were assigned to 3 groups: inseminated (control; n = 5), induced ovulation and inseminated (750 IU eCG, 500 IU hCG; n = 5), and superovulated and inseminated (1500 IU eCG, 1000 IU hCG; n = 5). Oviducts (isthmus and ampulla) were collected 3 days after phosphate-buffered saline treatment (experiment I) or insemination. Blood samples were collected during slaughter for E2 (estradiol) and P4 (progesterone) analysis. Levels of messenger RNA (mRNA) of the VEGF system were analyzed by real-time polymerase chain reaction and protein by Western blot and E2 and P4 using radioimmunoassays. Insemination by itself decreased VEGF120 mRNA expression and VEGF-A protein level in the oviductal isthmus (P < 0.05) but did not alter VEGF164 mRNA. Expression of Flt-1 (c-fms-like tyrosine kinase VEGFR-1) mRNA increased in the isthmus of inseminated relative to cyclic gilts (P < 0.05), whereas KDR (fetal liver kinase 1 VEGFR-2) mRNA levels decreased in both the oviductal isthmus (P < 0.05) and ampulla (P < 0.001). Superovulation decreased VEGF120 and VEGF164 mRNA expression in the isthmus compared with the inseminated group (P < 0.05), and lowered protein levels of VEGF-A in the isthmus of both stimulated groups (P < 0.001). Expression of Flt-1 mRNA was affected by hCG and eCG treatment in both gonadotropin-stimulated groups in the isthmus as well as in the ampulla (P < 0.001) and protein levels in the ampulla of superovulated gilts (P < 0.05). Protein levels of KDR were reduced in the oviductal ampulla of gilts in both the induced ovulation and superovulated groups (P < 0.05). The concentrations of both E2 and P4 increased significantly in superovulated group of gilts (P < 0.01 and P < 0.05 for E2 and P4, respectively). Our study showed that insemination alone as well as ovarian stimulation affected the mRNA and protein profiles of the VEGF system in the porcine oviduct. Disrupted VEGF system expression may be crucial to many events occurring during the periovulatory period and consequently could lead to deprivation of VEGF-dependent factors that are necessary for proper fertilization, gamete transport, and embryo development. PMID- 25124280 TI - The cost-effectiveness of installing sidewalks to increase levels of transport walking and health. AB - OBJECTIVE: This study investigated the cost-effectiveness of installing sidewalks to increase levels of transport-walking. METHODS: Secondary analysis using logistic regression established the association of sidewalks with transport walking using two transport-walking thresholds of 150 and 60 min/week using Western Australian data (n=1394) from 1995 to 2000. Minimum, moderate and maximum interventions were defined, associated respectively with one sidewalk, at least one sidewalk and sidewalks on both sides of the street. Costs, average and incremental cost-effectiveness ratios were calculated for each intervention and expressed as 'the cost per person who walks for transport for more than 150 min/week (60 min/week) after the installation of new sidewalks'. A sensitivity analysis examined the robustness of the incremental cost-effectiveness ratios to varying model inputs. Costs are in 2012 Australian dollars. RESULTS: A positive relationship was found between the presence of sidewalks and transport-walking for both transport-walking thresholds of 150 and 60 min/week. The minimum intervention was found to be the most cost-effective at $2330/person and $674/person for the 150 and 60 min/week transport-walking thresholds respectively. Increasing the proportion of people transport-walking and increasing population density by 50% improved the cost-effectiveness of installing side-walks to $346/person. CONCLUSIONS: To increase levels of transport-walking, retrofitting streets with one sidewalk is most cost-effective. PMID- 25124279 TI - Using electronic health record data to evaluate preventive service utilization among uninsured safety net patients. AB - OBJECTIVE: This study compared the preventive service utilization of uninsured patients receiving care at Oregon community health centers (CHCs) in 2008 through 2011 with that of continuously insured patients at the same CHCs in the same period, using electronic health record (EHR) data. METHODS: We performed a retrospective cohort analysis, using logistic mixed effects regression modeling to calculate odds ratios and rates of preventive service utilization for patients without insurance, or with continuous insurance. RESULTS: CHCs provided many preventive services to uninsured patients. Uninsured patients were less likely than continuously insured patients to receive 5 of 11 preventive services, ranging from OR 0.52 (95% CI: 0.35-0.77) for mammogram orders to 0.75 (95% CI: 0.66-0.86) for lipid panels. This disparity persisted even in patients who visited the clinic regularly. CONCLUSION: Lack of insurance is a barrier to preventive service utilization, even in patients who can access care at a CHC. Policymakers in the United States should continue to address this significant prevention disparity. PMID- 25124281 TI - Online reports of foodborne illness capture foods implicated in official foodborne outbreak reports. AB - OBJECTIVE: Traditional surveillance systems capture only a fraction of the estimated 48 million yearly cases of foodborne illness in the United States. We assessed whether foodservice reviews on Yelp.com (a business review site) can be used to support foodborne illness surveillance efforts. METHODS: We obtained reviews from 2005 to 2012 of 5824 foodservice businesses closest to 29 colleges. After extracting recent reviews describing episodes of foodborne illness, we compared implicated foods to foods in outbreak reports from the U.S. Centers for Disease Control and Prevention (CDC). RESULTS: Broadly, the distribution of implicated foods across five categories was as follows: aquatic (16% Yelp, 12% CDC), dairy-eggs (23% Yelp, 23% CDC), fruits-nuts (7% Yelp, 7% CDC), meat-poultry (32% Yelp, 33% CDC), and vegetables (22% Yelp, 25% CDC). The distribution of foods across 19 more specific food categories was also similar, with Spearman correlations ranging from 0.60 to 0.85 for 2006-2011. The most implicated food categories in both Yelp and CDC were beef, dairy, grains-beans, poultry and vine stalk. CONCLUSIONS: Based on observations in this study and the increased usage of social media, we posit that online illness reports could complement traditional surveillance systems by providing near real-time information on foodborne illnesses, implicated foods and locations. PMID- 25124283 TI - Versatile iridicycle catalysts for highly efficient and chemoselective transfer hydrogenation of carbonyl compounds in water. AB - Cyclometalated iridium complexes are shown to be highly efficient and chemoselective catalysts for the transfer hydrogenation of a wide range of carbonyl groups with formic acid in water. Examples include alpha-substituted ketones (alpha-ether, alpha-halo, alpha-hydroxy, alpha-amino, alpha-nitrile or alpha-ester), alpha-keto esters, beta-keto esters and alpha,beta-unsaturated aldehydes. The reduction was carried out at substrate/catalyst ratios of up to 50 000 at pH 4.5 and required no organic solvent. The protocol provides a practical, easy and efficient way for the synthesis of beta-functionalised secondary alcohols, such as beta-hydroxyethers, beta-hydroxyamines and beta-hydroxyhalo compounds, which are valuable intermediates in pharmaceutical, fine chemical, perfume and agrochemical synthesis. PMID- 25124285 TI - Fungal surgical site infections. PMID- 25124282 TI - Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer. AB - Poly (ADP) ribose polymerase (PARP) plays a key role in DNA repair and is highly expressed in small cell lung cancer (SCLC). We investigated the therapeutic impact of PARP inhibition in SCLC. In vitro cytotoxicity of veliparib, cisplatin, carboplatin, and etoposide singly and combined was determined by MTS in 9 SCLC cell lines (H69, H128, H146, H526, H187, H209, DMS53, DMS153, and DMS114). Subcutaneous xenografts in athymic nu/nu mice of H146 and H128 cells with relatively high and low platinum sensitivity, respectively, were employed for in vivo testing. Mechanisms of differential sensitivity of SCLC cell lines to PARP inhibition were investigated by comparing protein and gene expression profiles of the platinum sensitive and the less sensitive cell lines. Veliparib showed limited single-agent cytotoxicity but selectively potentiated (>= 50% reduction in IC50 ) cisplatin, carboplatin, and etoposide in vitro in five of nine SCLC cell lines. Veliparib with cisplatin or etoposide or with both cisplatin and etoposide showed greater delay in tumor growth than chemotherapy alone in H146 but not H128 xenografts. The potentiating effect of veliparib was associated with in vitro cell line sensitivity to cisplatin (CC = 0.672; P = 0.048) and DNA-PKcs protein modulation. Gene expression profiling identified differential expression of a 5-gene panel (GLS, UBEC2, HACL1, MSI2, and LOC100129585) in cell lines with relatively greater sensitivity to platinum and veliparib combination. Veliparib potentiates standard cytotoxic agents against SCLC in a cell-specific manner. This potentiation correlates with platinum sensitivity, DNA-PKcs expression and a 5-gene expression profile. PMID- 25124284 TI - Clinical, lifestyle, socioeconomic determinants and rate of asymptomatic intracranial atherosclerosis in stroke free Pakistanis. AB - BACKGROUND: Intracranial Atherosclerotic Disease (ICAD) is the most frequent etiology of stroke with high prevalence among Asians. Despite this, early determinants of ICAD have not been described from this region. METHODS: The study is an analytical prospective cross-sectional study of 200 adults from Radiology Departments of two diagnostic centers in Karachi. Eligible participants confirmed the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS) and underwent an interview covering medical, socio demographic, lifestyle and anthropometric evaluation using locally validated and standardized definitions. Magnetic Resonance Images (MRI) were centrally reviewed to detect ICAD using the criterion used in the Warfarin-Aspirin Symptomatic Intracranial Disease study. The risk factors associated with asymptomatic ICAD are reported along with prevalence ratios. RESULTS: Of the 200 participants, ICAD was found in 34.5% (n = 69) of the participants. Mean age was 37.1 (S.D 15.1) years with 62% younger than 45 years. Self-reported hypertension was found in 26.5% subjects, diabetes in 9%, dyslipidemia in 5% and depression in 60%. Smokeless tobacco (Adjusted PR 3.27 (1.07-6.05)), Western diet, high socioeconomic status (Adjusted PR 2.26 (1.99-5.62)) and dyslipidemia (Adjusted PR 1.88 (1.25-2.21)) had significant associations with ICAD after multivariable analysis. Age, gender, diabetes, hypertension, depression and physical activity did not have a significant association. CONCLUSION: ICAD was found on MRI in one in three asymptomatic Pakistanis and was associated with modifiable risks. Initiatives targeting primary prevention may be able to decrease the burden of disease caused by stroke due to ICAD. STUDY REGISTRATION NUMBER: NCT02072876 2/25/2014. PMID- 25124287 TI - Moving stem cell therapy to patients with idiopathic pulmonary fibrosis. PMID- 25124286 TI - An image processing approach to analyze morphological features of microscopic images of muscle fibers. AB - We present an image processing approach to automatically analyze duo-channel microscopic images of muscular fiber nuclei and cytoplasm. Nuclei and cytoplasm play a critical role in determining the health and functioning of muscular fibers as changes of nuclei and cytoplasm manifest in many diseases such as muscular dystrophy and hypertrophy. Quantitative evaluation of muscle fiber nuclei and cytoplasm thus is of great importance to researchers in musculoskeletal studies. The proposed computational approach consists of steps of image processing to segment and delineate cytoplasm and identify nuclei in two-channel images. Morphological operations like skeletonization is applied to extract the length of cytoplasm for quantification. We tested the approach on real images and found that it can achieve high accuracy, objectivity, and robustness. PMID- 25124289 TI - Acute renal failure as a form of presentation of sarcoidosis in a young adult: a case report. AB - INTRODUCTION: Sarcoidosis is a systemic granulomatous disease. Renal involvement is a rare initial presentation of this disease. Few articles on renal involvement as an initial presentation of sarcoidosis have been published in the literature. CASE PRESENTATION: A 26-year-old Caucasian woman presented with acute renal failure as an initial manifestation of sarcoidosis. CONCLUSIONS: Renal involvement is an uncommon feature of sarcoidosis and it is essential to establish a fast and correct diagnosis because early therapy avoids progression to terminal renal failure. PMID- 25124288 TI - Physiological and proteomic analyses of salt stress response in the halophyte Halogeton glomeratus. AB - Very little is known about the adaptation mechanism of Chenopodiaceae Halogeton glomeratus, a succulent annual halophyte, under saline conditions. In this study, we investigated the morphological and physiological adaptation mechanisms of seedlings exposed to different concentrations of NaCl treatment for 21 d. Our results revealed that H. glomeratus has a robust ability to tolerate salt; its optimal growth occurs under approximately 100 mm NaCl conditions. Salt crystals were deposited in water-storage tissue under saline conditions. We speculate that osmotic adjustment may be the primary mechanism of salt tolerance in H. glomeratus, which transports toxic ions such as sodium into specific salt-storage cells and compartmentalizes them in large vacuoles to maintain the water content of tissues and the succulence of the leaves. To investigate the molecular response mechanisms to salt stress in H. glomeratus, we conducted a comparative proteomic analysis of seedling leaves that had been exposed to 200 mm NaCl for 24 h, 72 h and 7 d. Forty-nine protein spots, exhibiting significant changes in abundance after stress, were identified using matrix-assisted laser desorption ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS/MS) and similarity searches across EST database of H. glomeratus. These stress-responsive proteins were categorized into nine functional groups, such as photosynthesis, carbohydrate and energy metabolism, and stress and defence response. PMID- 25124290 TI - The ability to suppress macrophage-mediated inflammation in orbital fat stem cells is controlled by miR-671-5p. AB - INTRODUCTION: Our previous works demonstrated that systemic orbital fat-derived stem cell (OFSC) transplantation was effective in ameliorating lipopolysaccharide (LPS)-induced extensive acute lung injury (ALI) in vivo mainly through paracrine regulation of macrophage-mediated cytokine-storm. In this study, we explore the molecular mechanism(s) of OFSCs regulating macrophage activity in a cytokine inducible fashion. METHODS: LPS (100 ng/ml)-activated macrophages were treated by conditioned medium from OFSCs (OFSCs-CM) or non-contact cultured with OFSCs for 6 hours. The potency of OFSCs on macrophage proliferation and pro-inflammation ability were determined. Expression levels of pro-inflammatory cytokines in macrophages, inducible immuno-modulatory factors in OFSCs, were investigated. Deep sequencing analysis as well as interaction between microRNA (miRNA) and genes of immuno-modulators in OFSCs induced by activated macrophages was predicted by miRTar. Transfection of miRNA inhibitor into OFSCs was performed. Real-time RT-PCR and transplantation of OFSCs into mice with LPS-induced ALI confirmed the in vitro and in vivo mechanism. RESULTS: The paracrine effect of OFSCs on inhibition of macrophage pro-inflammatory cytokine release was more potent than induction of macrophage G0/G1 cell cycle arrest. OFSCs-CM suppressed LPS-induced inducible nitric oxide synthetase and the pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 alpha, and IL 1 beta expression in macrophages. Under non-contact culture, LPS-activated macrophages effectively triggered the expression of soluble immuno-modulating factors in OFSCs, i.e., IL-10, IL-1 receptor antagonist (IL-1 RA), indoleamine 2,3-dioxygenase, and soluble TNF receptor type II (sTNF RII). Under miRTar prediction, miR-671-5p was identified as a critical microRNA in regulation of multiple immune-modulating factors in OFSCs response to macrophages. The baseline level of miR-671-5p was high in OFSCs, and down-regulation of miR-671-5p upon co culture with activated macrophages was observed. MiR-671-5p inhibitor transfection into OFSCs selectively enhanced the IL-1 RA and sTNF RII expressions. In addition, inhibition of miR-671-5p in OFSCs enhanced the anti inflammatory ability against LPS-induced ALI. CONCLUSION: The paracrine effect of OFSCs inhibits the pro-inflammatory ability and proliferation of macrophages. The immune-modulation capacity of OFSCs can be triggered by activated macrophages, and down-regulation of miR-671-5p enhances OFSC immuno-modulation ability by up regulating IL-1 RA and sTNF RII expression. PMID- 25124291 TI - Switching to emtricitabine, tenofovir and rilpivirine as single tablet regimen in virologically suppressed HIV-1-infected patients: a cohort study. AB - OBJECTIVES: Emtricitabine/tenofovir/rilpivirine as a single-tablet regimen (STR) is widely used without licence in treatment-experienced patients. The purpose of this retrospective observational study was to assess viral suppression of ART experienced patients switching to STR. METHODS: We assessed 131 pretreated patients switching to STR with HIV RNA <400 HIV-1 RNA copies/mL. The primary outcome measure was the proportion of patients at week 24 with HIV RNA <40 copies/mL. RESULTS: By week 24, eight patients had stopped STR: four because of adverse events and four for other reasons. Three virological failures were observed; among these, at least one patient developed cross-resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), in particular with the E138K pattern. In intent-to-treat analysis, 92% of participants (120 of 131) achieved HIV RNA <40 copies/mL. Only grade 1 to 2 adverse events were observed, mainly consisting of increased liver enzymes (n=33). Systemic exposure to rilpivirine was above the usually observed steady-state levels for the 18 measurements assessed. CONCLUSIONS: Efficacy and tolerability are similar to those in treatment-naive patients. PMID- 25124293 TI - Psychological factors predicting outcome after traumatic injury: the role of resilience. AB - BACKGROUND: Increasingly, studies have examined the psychological impact on individuals who survive a traumatic physical injury. The primary aim of this study was to determine the stability of resilience and its association with depressive symptoms. METHODS: This study included 110 adults admitted to a Level I trauma center. Resilience and depression were measured at baseline and 12 months. Injury-related variables included Glasgow Coma Scale, Injury Severity Score, etiology of injury, and type of injury. RESULTS: Analysis revealed that resilience remained stable over 12 months regardless of injury severity, etiology, or type. Negative correlations were found between baseline resilience and 12-month depression (P < .01), as well as Glasgow Coma Scale and depression (P = .001). CONCLUSIONS: Injured individuals with low resilience are more likely to be depressed at 12 months. Assessing resilience at the time of injury may be useful in identifying those at risk for depression 1 year later. PMID- 25124294 TI - Perihilar cholangiocarcinoma: paradigms of surgical management. AB - Cholangiocarcinoma is a lethal disease with increasing incidence worldwide. Perihilar cholangiocarcinoma represents the most common type of cholangiocarcinoma. Despite major development on surgical strategies over the past 20 years, the 5-year survival rate after surgery has remained below 40%, often in the vicinity of 20%. Most perihilar cholangiocarcinomas, however, are unresectable at the time of the diagnosis. The recent use of aggressive approaches based on better image modality, specific perioperative management, and a multidisciplinary approach have enabled to convert the use of palliative therapies to more radical surgery. This review focuses on the recent advances in surgical treatment for perihilar cholangiocarcinoma including liver transplantation with their respective impact on patient survival. PMID- 25124292 TI - Does intramesorectal excision for ulcerative colitis impact bowel and sexual function when compared with total mesorectal excision? AB - BACKGROUND: Proctectomy for ulcerative colitis (UC) can be performed via intramesorectal (IME) or total mesorectal excision (TME). METHODS: We compared patient-reported bowel and sexual function among IME versus TME UC patients (September 2000 to March 2011) using the Memorial Sloan-Kettering Cancer Center Bowel Function scale, Fecal Incontinence Quality of Life, Fecal Incontinence Severity Index, Female Sexual Function Instrument, and International Index of Erectile Dysfunction surveys. RESULTS: Eighty-nine IME versus TME patients (35 +/ 2 years, 57% male, 62% IME) had similar baseline characteristics, although IME patients had more open procedures (P <= .03). IME patients reported better fecal continence (P = .009) but similar fecal incontinence-related quality of life (P >= .44). For sexual function, there were no differences for either women (Female Sexual Function Instrument; P >= .20) or men (International Index of Erectile Dysfunction; P >= .22). CONCLUSIONS: IME appears to be associated with better fecal continence but no difference in overall bowel or sexual function compared with TME in patients with UC. PMID- 25124296 TI - Triple opportunistic pulmonary cavitary disease after cord blood transplantation. AB - Opportunistic infectious diseases in patients are variable and depend on the host as well as the type of immunosuppression. Cord blood transplant recipients appear to be particularly vulnerable to infectious complications. Sequential or concurrent opportunistic infectious diseases can be particularly difficult to manage and have increased mortality. We present a young patient, status post cord blood transplantation for acute myelogenous leukemia, who developed a large pulmonary mass-like infection with Aspergillus, cytomegalovirus, and Mycobacterium avium complex. Radiological, surgical, and pathological features are described. PMID- 25124295 TI - The effect of antecolic versus retrocolic reconstruction on delayed gastric emptying after classic non-pylorus-preserving pancreaticoduodenectomy. AB - BACKGROUND: Delayed gastric emptying (DGE) after pancreaticoduodenectomy increases length of hospital stay and costs, and may be influenced by surgical techniques. METHODS: We retrospectively compared 400 patients with antecolic gastrojejunostomy with 400 patients with retrocolic gastrojejunostomy for the occurrence of DGE. RESULTS: The prevalence of DGE was 15% in the antecolic group and 21% in the retrocolic group (P = .021), and median length of stay was shorter for the former (8 vs. 10 days, P = .001). The difference was statistically significant with grade A DGE (9% vs. 14%, P = .038), but not B or C. In a multivariate analysis, DGE was influenced by retrocolic reconstruction, as well as older age, chronic pancreatitis, preoperative bilirubin level, a history of previous upper abdominal surgery, and postoperative pancreatic fistula. CONCLUSIONS: An antecolic gastrojejunostomy for classic non-pylorus-preserving pancreaticoduodenectomy is associated with a lower incidence of mild DGE (grade A) and a shorter length of stay. PMID- 25124297 TI - Review: Bone conduction devices and contralateral routing of sound systems in single-sided deafness. AB - OBJECTIVES/HYPOTHESIS: Systematically review the literature on the clinical outcome of bone conduction devices (BCD) and contralateral routing of sound systems (CROSS) for patients with single-sided deafness (SSD). DATA SOURCES: PubMed, Embase, Cochrane Library, and CINAHL databases were searched up to April 7, 2014. REVIEW METHODS: All studies investigating BCD and CROSS for patients with SSD on speech perception in noise, sound localization, or quality of life were selected and critically appraised. RESULTS: In total, 46 articles were retrieved, of which six satisfied the eligibility criteria. Critical appraisal showed that five studies (n = 91) carried a moderate to high directness of evidence and a low to moderate risk of bias. Subsequently, study characteristics and outcome measurements were extracted. Due to large heterogeneity between studies, pooling of data was not feasible. Studies did not show a clear advantage of BCD or CROSS on speech perception in noise. BCD and CROSS lead to the same sound localization ability as the unaided condition. Quality of life did not differ significantly between conditions; however, subjective speech communication did improve. CONCLUSION: No high level of evidence studies compare BCD and CROSS in patients with SSD. Literature showed no beneficial effect of BCD or CROSS regarding speech perception in noise and sound localization. Subjective speech communication demonstrated a moderate improvement with BCD and CROSS. High evidence studies comparing all treatment options for single-sided deafness should be conducted. PMID- 25124298 TI - An evaluation of interactive computer training to teach instructors to implement discrete trials with children with autism. AB - Discrete-trial instruction (DTI) is a teaching strategy that is often incorporated into early intensive behavioral interventions for children with autism. Researchers have investigated time- and cost-effective methods to train staff to implement DTI, including self-instruction manuals, video modeling, and interactive computer training (ICT). ICT combines the best components of self instruction manuals and video models, and have the same benefits; however, there is limited research on this training method. Therefore, the purpose of this study was to investigate ICT to teach university students to implement DTI with children with autism. All participants' teaching fidelity increased during both role-plays with an adult and instructional sessions with a child with autism. In addition, participants demonstrated an increase in teaching fidelity with untrained instructional programs. All participants were able to complete training in an average of 2 hr, and social validity ratings were high. PMID- 25124299 TI - Diaphragmatic hernia after liver transplantation in children: case series and review of the literature. AB - A diaphragmatic hernia (DH) is a rare complication of pediatric liver transplantation (LT), with multiple factors implicated in the pathophysiology. It is a potentially life-threatening condition in the absence of early recognition and surgical treatment. A DH after LT has been reported in 16 patients in 7 case series. We report 10 cases from our institution and review the published literature to understand the underlying pathophysiology. The study sample included all children (<18 years of age) who underwent LT from October 1989 to August 2013 at our center and subsequently presented with a DH. Among 4433 LT procedures performed in this time period, 1032 were for children. Ten DH cases were recognized, and risk factors were assessed. The mean age at diagnosis was 4.9 years, all patients with a DH received left lateral segment split grafts, and the mean graft weight was 248 +/- 41 g with a mean graft-to-recipient body weight ratio (GBWR) of 3% +/- 1.22% (range = 1.7%-5.0%). The mean cold ischemia time was 510.7 +/- 307.6 minutes (range = 60-900 minutes). Six patients had a primary abdominal muscle closure, 3 had a temporary Silastic mesh closure, and 1 had a skin closure only. Postoperative ascites and pleural effusion did not appear to be significant risk factors. All 10 children presented with a right posterolateral DH, with 1 also having a left DH. The small bowel was herniated in the majority. All patients underwent prompt surgical intervention without complications. An early age, a split graft, and a high GBWR may be risk factors for a DH. A high index of suspicion and prompt surgical intervention minimize complications. PMID- 25124300 TI - Vertically-aligned BCN nanotube arrays with superior performance in electrochemical capacitors. AB - Electrochemical capacitors (EC) have received tremendous interest due to their high potential to satisfy the urgent demand in many advanced applications. The development of new electrode materials is considered to be the most promising approach to enhance the EC performance substantially. Herein, we present a high capacity capacitor material based on vertically-aligned BC2N nanotube arrays (VA BC2NNTAs) synthesized by low temperature solvothermal route. The obtained VA BC2NNTAs display the good aligned nonbuckled tubular structure, which could indeed advantageously enhance capacitor performance. VA-BC2NNTAs exhibit an extremely high specific capacitance, 547 Fg(-1), which is about 2-6 times larger than that of the presently available carbon-based materials. Meanwhile, VA BC2NNTAs maintain an excellent rate capability and high durability. All these characteristics endow VA-BC2NNTAs an alternative promising candidate for an efficient electrode material for electrochemical capacitors (EC). PMID- 25124301 TI - Conjugate umpolung of beta,beta-disubstituted enals by dual catalysis with an N heterocyclic carbene and a Bronsted acid: facile construction of contiguous quaternary stereocenters. AB - A sterically hindered homoenolate has been generated by the NHC-catalyzed conjugate umpolung of beta,beta-disubstituted enals and successfully employed in a facile stereoselective annulation with isatins. The strategy provides efficient access to spirocyclic oxindoles bearing two highly congested contiguous quaternary carbon centers. The use of a Bronsted acid cocatalyst was found to be crucial for guaranteeing both excellent reactivity and high stereoselectivity. PMID- 25124302 TI - The effect of environment on nursing and health promotion for women. PMID- 25124306 TI - Nasal reconstruction: a dermatological surgeon's approach to recreating the 'aesthetic king' of the central face. PMID- 25124303 TI - Correlates of polysomnographic sleep changes in cocaine dependence: self administration and clinical outcomes. AB - BACKGROUND: Abstinence from chronic cocaine use is associated with abnormal sleep architecture. As sleep abnormalities are associated with clinical outcome in alcohol dependence, we hypothesized a similar relationship in cocaine dependence. METHODS: We report data from a cocaine self-administration study (N=12) and the placebo arm of a randomized clinical trial (N=20). Self-administration participants underwent three cocaine self-administration sessions during a three week inpatient stay. Treatment participants underwent two weeks of inpatient followed by six weeks of outpatient treatment including once-weekly cognitive behavioral therapy. Measurements included polysomnography from early and late in abstinence during the inpatient stays. Clinical outcomes included amount of cocaine self-administered, urine tests, and self-reported use and withdrawal symptoms. RESULTS: Change in slow-wave sleep from early to late abstinence (DeltaSWS; p=0.05), late abstinence rapid eye movement sleep (REM; p=0.002), and late abstinence total sleep time (p=0.02) were negatively correlated with the amount of cocaine self-administered. Early abstinence REM was positively correlated with withdrawal symptoms (p=0.02). Late abstinence REM was positively correlated with percent negative urines and maximum consecutive number of days abstinent (both p<0.001). DeltaSWS was positively correlated with percent negative urines (p=0.03) and participants with increased SWS had greater percent negative urines (p=0.008) and maximum consecutive number of days abstinent (p=0.009). CONCLUSIONS: Correlations between sleep deficits and amount of cocaine self-administered, clinical outcomes, and severity of withdrawal symptoms underscore the relevance of sleep in clinical outcomes in the treatment of cocaine dependence. PMID- 25124304 TI - Smoking, MATRICS consensus cognitive battery and P50 sensory gating in a Han Chinese population. AB - BACKGROUND: The effects of smoking on cognitive performance have long been studied, with mixed results. P50 sensory gating has been used as endophenotype for studying nicotinic systems genetics, and P50 gating deficits have been reported to be a sensitive biomarker for cognitive impairment in schizophrenia. This study examined the inter-relationship between P50 suppression, cognitive function, and smoking in a healthy Han Chinese population, which has not been reported before. METHODS: We recruited 82 healthy male subjects, including 48 smokers and 34 non-smokers who were matched for age and education. The authors measured P50 sensory gating and administered the Chinese-language version of the MATRICS consensus cognitive battery (MCCB) and Stroop tests. RESULTS: The results showed that the smokers scored lower than nonsmokers on the MCCB brief visuospatial memory test (BVMT) index and the STROOP test. Furthermore, the MCCB total score was negatively associated with number of cigarettes smoked per day in the smoker group. However, P50 sensory gating was not associated with either smoking status or any cognitive performance. CONCLUSIONS: Our results show that smoking is associated with cognitive impairment, but not with P50 sensory gating. PMID- 25124308 TI - Reconstructing the nasal dorsum. AB - The skin of the nasal dorsum and bridge is more forgiving in terms of reconstructive options. Individual differences in skin laxity, nasal length and sebaceous composition impact on reconstructive choice as do the size, depth and exact location of the surgical defect. For many, if not all, defects in this area there are multiple different reconstructive options available all of which can result in equivalent and excellent results. Oftentimes there is no clear advantage of one repair over another and the choice becomes one of personal preference based on experience. No proscriptive approach or algorithm can be usefully applied in this setting. Key considerations include the location of the defect (distal vs. proximal nasal dorsum), the position of the defect (midline or off-centre) and the texture of the skin involved (sebaceous vs. non-sebaceous). Defects may be considered complex if they border on, or cross onto adjacent cosmetic units. Examples include defects extending onto the nasal tip, tip-ala junction, sidewall, nasal root-glabella and medial canthus. The adjacent reservoirs of tissue redundancy that can be utilized in flap reconstruction include the nasal sidewall, the nasal dorsum itself, the glabella, the midline/paramedian forehead and the medial cheek. Nearly all flaps on the nasal dorsum require subnasalis muscle dissection to effect sufficient movement and to ensure adequate flap vascularity and viability. The nasal bridge and glabella have much thicker skin and it is usually sufficient to dissect in the subcutaneous plane rather than disrupting the deeper procerus and corrugator muscles. Thick sebaceous skin is generally stiffer, moves less easily and closures may result in greater wound tension. These factors together with a tendency for sutures to tear through easily potentially increases the risk of complications. Greater consideration should be given to the exact type of flap or graft chosen in these patients. PMID- 25124305 TI - Separate and combined effects of the GABAA positive allosteric modulator diazepam and Delta9-THC in humans discriminating Delta9-THC. AB - BACKGROUND: Our previous research suggested the involvement of gamma-aminobutyric acid (GABA), in particular the GABAB receptor subtype, in the interoceptive effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC). The aim of the present study was to determine the potential involvement of the GABAA receptor subtype by assessing the separate and combined effects of the GABAA positive allosteric modulator diazepam and Delta(9)-THC using pharmacologically selective drug discrimination procedures. METHODS: Ten cannabis users learned to discriminate 30 mg oral Delta(9)-THC from placebo and then received diazepam (5 and 10mg), Delta(9)-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self report, task performance and physiological measures were also collected. RESULTS: Delta(9)-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug) and elevated heart rate. Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report questionnaire items (e.g., Any Effect, Sedated), but did not substitute for the Delta(9)-THC discriminative stimulus or alter the Delta(9)-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of Delta(9)-THC. CONCLUSIONS: These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Delta(9)-THC, and by extension cannabis, in humans. PMID- 25124307 TI - Nasal anatomy for the dermatological surgeon. AB - The nose is an important site of skin pathology and skin cancer in particular, underlining the importance of the nose to the practice of dermatology. This article is intended to serve as an overview of the anatomy of the nose for dermatologists and dermatological surgeons. Areas of clinical relevance are emphasized with examples. PMID- 25124310 TI - Reconstructing the nasal tip. AB - Given the intricate contours of adjacent concavities and convexities, the limited area from which to recruit similar skin, and variable areas of skin thickness, elasticity and adnexal density, reconstruction of the nasal tip is a challenging process. When approaching nasal reconstruction we have often found it helpful to partition defects into two subgroups: those that fall within the upper two-thirds of the nose and those that fall within the lower third. Within this framework of the lower third, we present our reconstructive approach to surgical defects of the nasal tip. PMID- 25124309 TI - Repair of the nasal sidewall. AB - Repair of the nasal sidewall after skin cancer excision is generally best approached with the use of local flaps for aesthetic reasons. The sidewall may be divided into upper and lower sections and defects described as small, medium or large. In this section I will review the flaps that I feel make best use of adjacent tissue reservoirs allowing aesthetic placement of incisions while protecting free margins and function, and that reward the operator with reliably superior results for the patient. PMID- 25124311 TI - The reconstruction of the nasal ala with interpolated flaps from the cheek and forehead: design and execution modifications to improve surgical outcomes. AB - The nasal ala, critically important in the function and appearance of the central face, has significant reconstructive demands given the lack of suitable adjacent donor tissue that can be used to repair all but the smallest surgical defects in this area. Interpolated flaps from the forehead and cheek have long been ideal reconstructive alternatives for the repair of larger or more difficult alar wounds, and with the design and execution modifications described here, the dermatological surgeon can offer more appropriate restoration of this critically important aesthetic unit. PMID- 25124312 TI - Multiresidue determination of UV filters in water samples by solid-phase extraction and liquid chromatography with tandem mass spectrometry analysis. AB - UV filters, contained in sunscreens and other cosmetic products, as well as in some plastics and industrial products, are nowadays considered contaminants of emerging concern because their widespread and increasing use has lead to their presence in the environment. Furthermore, some UV filters are suspected to have endocrine disruption activity. In the present work, we developed an analytical method based on liquid chromatography with tandem mass spectrometry for the determination of UV filters in tap and lake waters. Sixteen UV filters were extracted from water samples by solid-phase extraction employing graphitized carbon black as adsorbent material. Handling 200 mL of water sample, satisfactory recoveries were obtained for almost all the analytes. The limits of detection and quantification of the method were comparable to those reported in other works, and ranged between 0.7-3.5 and 1.9-11.8 ng/L, respectively; however in our case the number of investigated compounds was larger. The major encountered problem in method development was to identify the background contamination sources and reduce their contribution. UV filters were not detected in tap water samples, whereas the analyses conducted on samples collected from three different lakes showed that the swimming areas are most subject to UV filter contamination. PMID- 25124313 TI - Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management. AB - DISEASE OVERVIEW: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell-derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival. DIAGNOSIS: DIAGNOSIS is based on bone marrow morphology. The presence of JAK2, CALR, or MPL mutation is supportive but not essential for diagnosis; approximately 90% of patients carry one of these mutations and 10% are "triple-negative." None of these mutations are specific to PMF and are also seen in essential thrombocythemia (ET). Prefibrotic PMF mimics ET in its presentation and the distinction, enabled by careful bone marrow morphological examination, is prognostically relevant. Differential diagnosis also includes chronic myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. RISK STRATIFICATION: The Dynamic International Prognostic Scoring System-plus (DIPSS-plus) uses eight predictors of inferior survival: age >65 years, hemoglobin <10 g/dL, leukocytes >25 * 10(9) /L, circulating blasts >=1%, constitutional symptoms, red cell transfusion dependency, platelet count <100 * 10(9) /L, and unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, -7/7q-, i(17q), inv(3), -5/5q-, 12p-, or 11q23 rearrangement). The presence of 0, 1, "2 or 3," and >=4 adverse factors defines low, intermediate-1, intermediate-2, and high-risk disease with median survivals of approximately 15.4, 6.5, 2.9, and 1.3 years, respectively. High risk disease is also defined by CALR(-) /ASXL1(+) mutational status. RISK-ADAPTED THERAPY: Observation alone is adequate for asymptomatic low/intermediate-1 risk disease, especially with CALR(+) /ASXL1(-) mutational status. Stem cell transplant is considered for DIPSS-plus high risk disease or any risk disease with CALR(-) /ASXL1(+) mutational status. Investigational drug therapy is reasonable for symptomatic intermediate-1 or intermediate-2 risk disease. Splenectomy is considered for drug-refractory splenomegaly. Involved field radiotherapy is most useful for post-splenectomy hepatomegaly, non-hepatosplenic EMH, PMF-associated pulmonary hypertension, and extremity bone pain. PMID- 25124314 TI - Response to the Letter-to-the-Editor Regarding "The Two Year Cost Effectiveness of Three Options to Treat Lumbar Spinal Stenosis Patients". PMID- 25124316 TI - Geometric accuracy in three-dimensional coordinates of Leksell stereotactic skull frame with wide-bore 1.5-T MRI compared with conventional 1.5-T MRI. AB - The use of 1.5-tesla (T) magnetic resonance (MR) imaging with a wide and simultaneously short bore enhances patient comfort compared with traditional 1.5 T MR imaging and is becoming increasingly available in stereotactic radiosurgery treatment planning. However, the geometric accuracy seems unavoidably worse in wide-bore MR imaging than in conventional MR imaging. We assessed the geometric distortion of the stereotactic image attached on a Leksell skull frame in conventional and wide-bore 1.5-T MR imaging. Two kinds of acrylic phantoms were placed on the skull frame and were scanned using computed tomography (CT) and conventional and wide-bore 1.5-T MR imaging. The three-dimensional coordinates on both MR imaging were compared with those on CT. Deviations of measured coordinates at selected points (x = 50, 100, 150 mm; y = 50, 100, 150 mm) were indicated on different axial planes (z = 50, 75, 100, 125, 150 mm). The differences of coordinates were less than 1.0 mm in the entire treatable area for conventional MR imaging. With the large bore system, the differences of the coordinates were less than 1.0 mm around the center but substantially exceeded 1.0 mm in the peripheral regions. Further study is needed to increase the geometric accuracy of wide-bore MR imaging for stereotactic radiosurgery treatment planning. PMID- 25124315 TI - A single exposure to cocaine during development elicits regionally-selective changes in basal basic Fibroblast Growth Factor (FGF-2) gene expression and alters the trophic response to a second injection. AB - RATIONALE: During adolescence, the brain is maturing and more sensitive to drugs of abuse that can influence its developmental trajectory. Recently, attention has been focused on basic fibroblast growth factor (FGF-2) given that its administration early in life enhances the acquisition of cocaine self administration and sensitization at adulthood (Turner et al. (Pharmacol Biochem Behav 92:100-4, 2009), Clinton et al. (Pharmacol Biochem Behav103:6-17, 2012)). Additionally, we found that abstinence from adolescent cocaine exposure long lastingly dysregulates FGF-2 transcription (Giannotti et al. (Psychopharmacology (Berl) 225:553-60, 2013 ). OBJECTIVES: The objectives of the study are to evaluate if (1) a single injection of cocaine (20 mg/kg) at postnatal day 35 alters FGF-2 messenger RNA (mRNA) levels and (2) the first injection influences the trophic response to a second injection (10 mg/kg) provided 24 h or 7 days later. RESULTS: We found regional differences in the FGF-2 expression pattern as either the first or the second injection of cocaine by themselves upregulated FGF 2 mRNA in the medial prefrontal cortex and nucleus accumbens while downregulating it in the hippocampus. The first injection influences the trophic response of the second. Of note, 24 h after the first injection, accumbal and hippocampal FGF-2 changes produced by cocaine in saline-pretreated rats were prevented in cocaine pretreated rats. Conversely, in the medial prefrontal cortex and hippocampus 7 days after the first injection, the cocaine-induced FGF-2 changes were modified by the subsequent exposure to the psychostimulant. CONCLUSIONS: These findings show that a single cocaine injection is sufficient to produce enduring changes in the adolescent brain and indicate that early cocaine priming alters the mechanisms regulating the trophic response in a brain region-specific fashion. PMID- 25124317 TI - A detailed view on sulphur metabolism at the cellular and whole-plant level illustrates challenges in metabolite flux analyses. AB - Understanding the dynamics of physiological process in the systems biology era requires approaches at the genome, transcriptome, proteome, and metabolome levels. In this context, metabolite flux experiments have been used in mapping metabolite pathways and analysing metabolic control. In the present review, sulphur metabolism was taken to illustrate current challenges of metabolic flux analyses. At the cellular level, restrictions in metabolite flux analyses originate from incomplete knowledge of the compartmentation network of metabolic pathways. Transport of metabolites through membranes is usually not considered in flux experiments but may be involved in controlling the whole pathway. Hence, steady-state and snapshot readings need to be expanded to time-course studies in combination with compartment-specific metabolite analyses. Because of species specific differences, differences between tissues, and stress-related responses, the quantitative significance of different sulphur sinks has to be elucidated; this requires the development of methods for whole-sulphur metabolome approaches. Different cell types can contribute to metabolite fluxes to different extents at the tissue and organ level. Cell type-specific analyses are needed to characterize these contributions. Based on such approaches, metabolite flux analyses can be expanded to the whole-plant level by considering long-distance transport and, thus, the interaction of roots and the shoot in metabolite fluxes. However, whole-plant studies need detailed empirical and mathematical modelling that have to be validated by experimental analyses. PMID- 25124318 TI - Roles of melatonin in abiotic stress resistance in plants. AB - In recent years melatonin has emerged as a research highlight in plant studies. Melatonin has different functions in many aspects of plant growth and development. The most frequently mentioned functions of melatonin are related to abiotic stresses such as drought, radiation, extreme temperature, and chemical stresses. This review mainly focuses on the regulatory effects of melatonin when plants face harsh environmental conditions. Evidence indicates that environmental stress can increase the level of endogenous melatonin in plants. Overexpression of the melatonin biosynthetic genes elevates melatonin levels in transgenic plants. The transgenic plants show enhanced tolerance to abiotic stresses. Exogenously applied melatonin can also improve the ability of plants to tolerate abiotic stresses. The mechanisms by which melatonin alleviates abiotic stresses are discussed. PMID- 25124319 TI - Elevated levels of cyclooxygenase 1 and 2 in human cyclosporine induced gingival overgrowth. AB - OBJECTIVE: This study was carried out to immuno-localize and estimate the levels of cyclooxygenase 1 and 2 in human gingival tissue samples from healthy individuals, chronic periodontitis patients and patients with cyclosporine induced gingival overgrowth. METHODS: Group I consisted of individuals with healthy gingiva (n=6), Group II - cyclosporine induced gingival overgrowth (n=9) and Group III - chronic periodontitis patients (n=6). Gingival tissue samples were collected from subjects of all the three groups. COX-1, COX-2 levels were estimated in tissue homogenates by enzyme activity assay. Immuno-localization for COX-1 and COX-2 was also done in sections of gingival tissue. RESULTS: The study results demonstrated a significantly higher mean levels of COX-1 and 2 in drug induced gingival overgrowth samples (p<0.05). COX-1 and COX-2 was localized to epithelium and connective tissue in human gingival tissue sections from cyclosporine induced gingival overgrowth. CONCLUSION: Cyclooxygenase enzymes appear to be potential mediators involved in the pathogenesis of cyclosporine induced gingival overgrowth. PMID- 25124320 TI - Dynamic contrast enhanced MR imaging for rectal cancer response assessment after neo-adjuvant chemoradiation. AB - BACKGROUND: Patient selection for organ sparing treatment after good response to neo-adjuvant chemoradiation (CRT) for locally advanced rectal cancer is challenging as no optimal restaging modality is available after CRT. In this study, we assessed the value of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) for rectal cancer pathological response prediction. METHODS: In 51 patients with locally advanced rectal cancer, the tumor volume and volume transfer constant (Ktrans) were obtained at 3 Tesla before CRT and surgery. The predictive potential for pathological complete response (pCR) and good response (GR) was assessed. GR was defined as pCR and near-pCR based on the tumor regression grade. RESULTS: The GR group consisted of 10 patients (19.6%) with six pCR (11.8%). Both the post-CRT tumor volume and post-CRT Ktrans values and the relative change in volume (DeltaVolume) and Ktrans (DeltaKtrans) were predictive for pathological response. DeltaKtrans showed the best predictive potential with a positive predictive value (PPV) of 100% for GR using a cutoff value of 32% reduction in Ktrans. For pCR the best PPV was 80% with a multiparameter model containing DeltaVolume and DeltaKtrans. CONCLUSION: DCE-MRI has predictive potential for pathological response after CRT in rectal cancer with the relative DeltaKtrans being the most predictive parameter. PMID- 25124321 TI - Peeking into a cool future: genome editing to delete PCSK9 and control hypercholesterolemia in a single shot. PMID- 25124324 TI - Deepak Srivastava: follows his heart to study the heart. PMID- 25124323 TI - Study of exonic variation identifies incremental information regarding lipid related and coronary heart disease genes. PMID- 25124325 TI - Correction. PMID- 25124322 TI - Ceramide signaling in the coronary microcirculation: a double-edged sword? PMID- 25124326 TI - A novel variant in GABRB2 associated with intellectual disability and epilepsy. AB - The gamma-aminobutyric acid type A (GABAA ) receptor is one of the three main classes of receptors activated by GABA, the principal inhibitory neurotransmitter in the central nervous system. Mutations in genes encoding various subunits of this receptor (GABRA1, GABRA2, GABRA4, GABRA5, GABRA6, GABRB1, GABRB3, GABRG1, GABRG2, GABRG3, and GABRD) are implicated in a number of neurological and developmental disorders, including epilepsy and autism. To date, no human genetics studies have implicated mutations in GABRB2, encoding the beta2 subunit of the GABAA receptor, with neurodevelopmental disorders. Here we present a 12 year-old girl with intellectual disability and epilepsy, who was discovered by whole exome sequencing to have a de novo heterozygous missense variant in exon 4 of GABRB2 (c.236T>C; p.M79T). This variant is likely pathogenic, based on in silico analyses, as well as the fact that it results in the non-conservative substitution of a non-polar amino acid with a polar amino acid at a position that is evolutionarily conserved across multiple species. Our findings underscore the need for further investigation into the mechanisms by which mutations in GABRB2 contribute to neurological and developmental dysfunction. PMID- 25124327 TI - CDC Kerala 3: At-risk baby clinic service using different screening tools- outcome at 12 months using Developmental Assessment Scale for Indian Infants. AB - OBJECTIVES: To describe CDC Kerala experience of establishing an at-risk baby clinic and the comparison of different developmental screening tools at 12 mo against the gold standard Developmental Assessment Scale for Indian Infants (DASII). METHODS: At risk baby clinic of CDC, Kerala was established as a facility for follow up of NICU graduates from Sree Avittam Thirunal Hospital at 2, 4, 6, 8 and 12 mo corrected age and during each visit the mother is taught the CDC model early stimulation by developmental therapists and encouraged to continue to do the same at home. At 12 mo, assessment results of four simple developmental tools were compared with the gold standard DASII administered by a senior developmental therapist. RESULTS: Out of a total of 800 babies, outcome measurements at 12 mo were available for 604 infants. The prevalence of developmental delay using the screening tools, CDC grading for standing, Amiel Tison angles and DDST II (Denver II) gross motor were 24.8, 24 and 24.3% respectively and using DASII, a diagnostic tool (13.3%). Also the combination of Amiel Tison angles, CDC standing grading and DDST gross motor against DASII motor DQ had high specificity (94.15%) and negative predictive value (NPV) (70.18%) but with a very low sensitivity of 14.58% and low positive predictive value (PPV) of 53.85%. It was observed that a significant odds ratio for DASII mental deviation quotient (DQ) was seen for neonatal seizures (2.34) and low birth weight (1.49). CONCLUSION: The prevalence of developmental delay using the screening tools, CDC grading for standing, Amiel Tison angles and DDST II (Denver II) gross motor were 24.8, 24 and 24.3% respectively and together they had a high specificity, NPV and accuracy against DASII motor DQ as gold standard at one year assessment. PMID- 25124328 TI - CDC Kerala 5: Developmental therapy clinic experience--use of Child Development Centre grading for motor milestones. AB - OBJECTIVES: To document the experiences of the intervention given to children who attended the developmental therapy clinic of Child Development Centre (CDC) Kerala, a specialized clinic for providing developmental intervention/therapy for babies less than two years with developmental delay/disability. METHODS: All the babies referred to this speciality clinic from developmental screening/evaluation clinics of CDC were registered in the clinic and re-evaluation was done using CDC grading for head holding, sitting, standing, Amiel Tison passive angles, and Trivandrum Developmental Screening Chart (TDSC) 0-2 y. RESULTS: Out of a total of 600 consecutive babies below 2 y with developmental delay/disability referred to developmental therapy clinic, on comparing the test results at enrollment and after 6 mo of intervention, a statistically significant reduction was observed (i) in the 2-4 mo age group with regard to abnormal TDSC (25.5%), (ii) in the 4-8 mo age group with regard to abnormal head holding grade (87.1%) and abnormal TDSC (19.4%), (iii) in the 8-12 mo age group, with regard to abnormal sitting grade (71.7%) and (iv) in the above 12 mo age group with regard to abnormal sitting grade (35.3%) and abnormal standing grade (78.8%). CONCLUSIONS: The experience of organizing the developmental intervention/therapy clinic at CDC Kerala has shown that therapy services by developmental therapists in a centre and supportive therapy by mother at home is useful in improving the developmental status of children with developmental delay. PMID- 25124329 TI - Recent advances in neonatal seizures. AB - Neonatal seizures are the most important indicators of underlying brain injury. Seizures in a neonate are different from seizures in older children in many aspects including clinical presentation and etiology. The neonatal brain is immature and tends to have a decreased seizure threshold. Neonatal seizures are classified, based on their presentation as, clinical seizures, electroclinical seizures and electroencephalographic seizures; based on the pathophysiology as epileptic and nonepileptic seizures; and also on the basis of the etiology. Hypoxic ischemic encephalopathy is the leading cause of neonatal seizures, followed by intracranial hemorrhage, metabolic causes such as hypoglycemia and hypocalcemia, intracranial infections and strokes. Neonatal epilepsy syndromes are rare. Electroencephalography (EEG) is the gold standard for diagnosis. Amplitude integrated EEG (aEEG) is also used for continuous monitoring. The approach to management consists of initial stabilization of the neonate followed by treatment of potentially correctable injurious processes such as hypocalcemia, hypoglycemia and electrolyte disturbances, etiology specific therapies and antiepileptic drug (AED) therapy. Phenobarbital remains the first line AED therapy. Pharmacokinetic data on newer drugs is limited. Prognosis depends on the etiology, seizure type, neurological examination at discharge and EEG. Long term neurodevelopmental follow up is essential for babies with neonatal seizures. PMID- 25124330 TI - Protective effects of intranasal immunization with recombinant glycoprotein d in pregnant BALB/c mice challenged with different strains of equine herpesvirus 1. AB - Equine herpesvirus (EHV)-1 induces respiratory infection, neurological disorders and abortion in horses. Most of the currently available attenuated or inactivated vaccines against this infection are administered intramuscularly and only provide partial protection against the respiratory disease. The present study examines the effect of intranasal immunization with purified EHV-1 recombinant glycoprotein D (gD) in BALB/c mice followed by challenge with three different EHV 1 strains during early to mid-pregnancy. The induced viral infection was evaluated by virus isolation, DNA detection by polymerase chain reaction, histopathology and immunohistochemical localization of antigen in the lung, placenta and uterus. Non-immunized mice showed clinical signs of infection, positive virus isolation from lungs and uteri, and abortion induced by one of the virus strains. Endometrial lesions developed in some of these animals that have been described previously only in horses. Immunized mice and their offspring had no viral infection or typical lesions. Intranasally administered gD therefore induced partial or complete protection against three different EHV-1 strains in BALB/c mice. PMID- 25124331 TI - Oxidative modification, inflammation and amyloid in the normal and diabetic cat pancreas. AB - The pathogenesis of beta-cell dysfunction leading to pancreatic beta-cell failure seen in type 2 diabetes mellitus is incompletely understood. Pancreatic tissues were collected from nine control cats and nine diabetic cats and labelled immunohistochemically to examine expression of interleukin (IL)-1beta, insulin, islet amyloid polypeptide (IAPP) and 4-hydroxynonenal (4-HNE). Thioflavin-S was used to stain for amyloid. All control cats showed positive labelling for IL 1beta and 4-HNE. Diabetic cats showed varying degrees of inflammation and oxidative modification, owing in large part to the very small amount of islet structure remaining in the typical diabetic cat pancreas. Amyloid deposition was identified in 8/9 diabetic cats and 1/9 control cats. In order to validate these findings, paired biopsy samples taken from an additional group of cats enrolled in a study of obesity and hyperglycaemia (sampling at baseline and after 8-16 weeks of obesity and hyperglycaemia) were labelled for IL-1beta and 4-HNE. A similar pattern of labelling was identified in the baseline samples to that seen in control cats. A significant increase in IL-1beta and 4-HNE expression was seen after a period of hyperglycaemia and obesity. Taken together, these findings suggest that while present in normal cats, markers of inflammation and oxidative modification increase very early during the development of disease. Future studies focusing on these earlier time points are needed to understand the factors that function in protection of the islet beta cell and the development of islet pathology in type 2 diabetes mellitus in the cat. PMID- 25124332 TI - Candidate selection for quadrant-based focal ablation through a combination of diffusion-weighted magnetic resonance imaging and prostate biopsy. AB - OBJECTIVES: To identify prostatic quadrants that could be preserved without intervention, using diffusion-weighted magnetic resonance imaging (DWI) and extended core biopsy, as a step toward implementation of quadrant-based focal ablation with potential preservation of erectile and ejaculatory functions, based on comparisons with unilateral hemi-gland ablation. PATIENTS AND METHODS: We conducted a prebiopsy DWI study including 648 quadrants in 162 men who underwent 14-core biopsy including anterior sampling and radical prostatectomy (RP) for localised cancer. Imaging and pathology were analysed on a quadrant basis. Each quadrant was assessed through four-core sampling. Predictive performance of DWI and biopsy for quadrant status was analysed. RESULTS: On RP specimens, 170 anterior (52.5%) and 172 posterior quadrants (53.1%) harboured significant cancer. Negative predictive values of DWI, biopsy, and their combination for significant cancer were 79.7%, 70.6%, and 91.1%, respectively, in anterior quadrants, and 78.5%, 81.3%, and 91.7%, respectively, in posterior quadrants. DWI incrementally improved the negative predictive values of biopsy in anterior (P < 0.001) and posterior quadrants (P = 0.025), without untoward impacts on positive predictive values. Negative findings on both DWI and biopsy were identified in posterior quadrants of 109 sides (33.6%), but in entire hemi-glands of 54 sides (16.7%). CONCLUSIONS: The combination of DWI and 14-core biopsy including anterior sampling efficiently identifies quadrants without significant cancer in men with localised prostate cancer; the remaining quadrants, therefore, could be potential candidate areas for focal ablation. Focal therapy designed based on quadrant-based assessment could be superior to unilateral hemi-gland ablation for preservation of posterior quadrants and retaining of sexual function in more sides. PMID- 25124334 TI - Progress toward the total synthesis of N-methylwelwitindolinone B isothiocyanate. AB - Progress toward the welwitindolinone alkaloid N-methylwelwitindolinone B isothiocyanate is reported. A key reaction to synthesize the [4.3.1] bicycle embedded in the core of the molecule is a furan type 2 intramolecular Diels-Alder reaction with a tetrasubstituted dienophile, which sets the two vicinal quaternary centers present in the natural product. The sterically encumbered cycloaddition precursor was synthesized using a Horner-Wadsworth-Emmons reaction followed by a Suzuki cross-coupling reaction. Finally, introduction of the secondary alkyl chloride was achieved by a regio- and diastereoselective opening of a [2.2.1] oxobicycloheptane functionality. PMID- 25124333 TI - Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints. AB - BACKGROUND: Mitochondrial DNA (mtDNA) deletions cause disease and accumulate during aging, yet our understanding of the molecular mechanisms underlying their formation remains rudimentary. Guanine-quadruplex (GQ) DNA structures are associated with nuclear DNA instability in cancer; recent evidence indicates they can also form in mitochondrial nucleic acids, suggesting that these non-B DNA structures could be associated with mtDNA deletions. Currently, the multiple types of GQ sequences and their association with human mtDNA stability are unknown. RESULTS: Here, we show an association between human mtDNA deletion breakpoint locations (sites where DNA ends rejoin after deletion of a section) and sequences with G-quadruplex forming potential (QFP), and establish the ability of selected sequences to form GQ in vitro. QFP contain four runs of either two or three consecutive guanines (2G and 3G, respectively), and we identified four types of QFP for subsequent analysis: intrastrand 2G, intrastrand 3G, duplex derived interstrand (ddi) 2G, and ddi 3G QFP sequences. We analyzed the position of each motif set relative to either 5' or 3' unique mtDNA deletion breakpoints, and found that intrastrand QFP sequences, but not ddi QFP sequences, showed significant association with mtDNA deletion breakpoint locations. Moreover, a large proportion of these QFP sequences occur at smaller distances to breakpoints relative to distribution-matched controls. The positive association of 2G QFP sequences persisted when breakpoints were divided into clinical subgroups. We tested in vitro GQ formation of representative mtDNA sequences containing these 2G QFP sequences and detected robust GQ structures by UV-VIS and CD spectroscopy. Notably, the most frequent deletion breakpoints, including those of the "common deletion", are bounded by 2G QFP sequence motifs. CONCLUSIONS: The potential for GQ to influence mitochondrial genome stability supports a high priority investigation of these structures and their regulation in normal and pathological mitochondrial biology. These findings emphasize the potential importance of helicases that subsequently resolve GQ to maintain the stability of the mitochondrial genome. PMID- 25124335 TI - Incidence of retinopathy of prematurity in southwestern China and analysis of risk factors. AB - BACKGROUND: The aim of this study was to screen for retinopathy of prematurity (ROP) in southwestern China and understand the prevalence and risk factors of ROP, which may provide evidence useful in the prevention and treatment of ROP. MATERIAL/METHODS: 1864 preterm infants (gestational age of <37 weeks and birth weight of <=2500 g) underwent ROP screening from January 2009 to November 2012 in Southwest China. The medical information of infants during perinatal period was reviewed, and risk factors of ROP were determined. A total of 1614 infants were recruited for final analysis. RESULTS: Incidence of ROP was 12.8%. The first, second, third, and fourth stage of ROP was found in 64.6%, 29.6%, 3.4%, and 0.5% of infants, respectively. No fifth stage of ROP was observed. In addition, 7.7% of infants required surgical intervention. In our Department of Neonatology, the incidence of ROP was 20.0%, which was significantly higher than in non hospitalized patients (9.9%). The incidence of ROP remained unchanged over the years. Independent risk factors of ROP included low birth weight (p=0.049), low gestational age (p=0.008), days of oxygen supplementation (p=0.008), and myocardial injury after birth (p=0.001). CONCLUSIONS: The prevalence of ROP in preterm infants is relatively high in Southwest China, and low birth weight, low gestational age, days of oxygen supplementation, and myocardial injury after birth are independent risk factors for ROP. PMID- 25124337 TI - Carbazole-based hole-transport materials for efficient solid-state dye-sensitized solar cells and perovskite solar cells. AB - Two carbazole-based small molecule hole-transport materials (HTMs) are synthesized and investigated in solid-state dye-sensitized solar cells (ssDSCs) and perovskite solar cells (PSCs). The HTM X51-based devices exhibit high power conversion efficiencies (PCEs) of 6.0% and 9.8% in ssDSCs and PSCs, respectively. These results are superior or comparable to those of 5.5% and 10.2%, respectively, obtained for the analogous cells using the state-of-the-art HTM Spiro-OMeTAD. PMID- 25124336 TI - Sedentary behaviors, physical activity behaviors, and body fat in 6-year-old children: the generation R study. AB - BACKGROUND: Childhood overweight and obesity is a major public health concern. Knowledge on modifiable risk factors is needed to design effective intervention programs. This study aimed to assess associations of children's sedentary behaviors (television viewing and computer game use) and physical activity behaviors (sports participation, outdoor play, and active transport to/from school) with three indicators of body fat, i.e., percent fat mass, body mass index (BMI) standard deviation scores, and weight status (normal weight, overweight). METHODS: Cross-sectional data from 5913 6-year-old ethnically diverse children were analyzed. Children's weight and height were objectively measured and converted to BMI. Weight status was defined according to age- and sex-specific cut-off points of the International Obesity Task Force. BMI standard deviation scores were created, based on Dutch reference growth curves. Fat mass was measured my dual-energy X-ray absorptiometry (DXA). Sedentary and physical activity behaviors were assessed by parent-reported questionnaires. Series of logistic and linear regression analyses were performed, controlling for confounders (i.e., socio-demographic factors, family lifestyle factors, and other sedentary behaviors and physical activity behaviors). RESULTS: Sports participation was inversely associated with fat mass (p < 0.001), even after adjustment for socio-demographic factors, family lifestyle factors, and other sedentary behaviors and physical activity behaviors. No other independent associations were observed. CONCLUSIONS: The results of this study indicate that sports participation is inversely associated with percent body fat among ethnically diverse 6-year-old children. More research in varied populations including objective measurements and longitudinal designs are needed to confirm these current results. PMID- 25124338 TI - Adult neurogenesis: bridging the gap between mice and humans. AB - Neural stem/progenitor cells (NSPCs) generate new neurons in the mammalian brain throughout life. Over the past two decades, substantial progress has been made in deciphering the cellular and molecular mechanisms underlying adult neurogenesis and in understanding the role played by new neurons in brain function in animal models of health and disease. By contrast, knowledge regarding the extent and relevance of neurogenesis in the adult human brain remains scant. Here we review new concepts about how new neurons shape adult brain circuits, discuss fundamental, unanswered questions about stem cell-associated neural plasticity, and illustrate how the gap between the animal-based basic research and current efforts to analyze life-long neuronal development of the human brain may be overcome by using novel experimental strategies. PMID- 25124339 TI - Association between mental health disorders and sexual dysfunction in patients suffering from rheumatic diseases. AB - INTRODUCTION: Sexual functioning may be notoriously affected in patients suffering from rheumatic diseases, yet the extent to which physical and/or psychological factors contribute to sexual dysfunction in this particular group of patients remains underinvestigated. AIM: This cross-sectional study aimed at investigating whether an association exists between psychological status (anxiety, depression) and sexual dysfunction, independently of other physical factors, in patients with rheumatic disorders. METHODS: A total of 509 consecutive rheumatologic patients, aged 54.7 +/- 14.2 years, 423 female and 86 male, were studied. Female and male sexual function was evaluated with the Female Sexual Dysfunction Index (FSFI) and the International Index of Erectile Function (IIEF) questionnaire, respectively. The Hamilton Anxiety Scale and the Zung Self Rating Depression Scale were used to detect presence of anxiety and depression, respectively. MAIN OUTCOME MEASURES: Sexual dysfunction affected 69.9%, anxiety 37.5%, and depression 22% of our patients. RESULTS: A strong and negative correlation was found between anxiety and both FSFI (r = -0.169, P < 0.001) and IIEF score (r = -0.304, P = 0.004). Similarly, depressive symptomatology was strongly and negatively correlated with both FSFI (r = -0.178, P < 0.001) and IIEF score (r = -0.222, P = 0.04). In the logistic regression analysis, apart from increasing age and female sex, depression (P = 0.027) and anxiety (P = 0.049) were identified as the only predictors of sexual dysfunction, even after adjustment for a variety of physical factors. CONCLUSIONS: Mental distress and sexual dysfunction are extremely common in rheumatologic patients. Sexual dysfunction is significantly associated with anxiety and depression in both men and women and may be independently predicted by their presence in this group of patients. Physicians dealing with rheumatologic patients should be aware of these results and incorporate screening and treatment of the above comorbidities in the global assessment of their patients, in order to alleviate the disease-emerging mental and physical burden and improve their quality of life. PMID- 25124340 TI - Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations: a topical review. AB - In contemporary post-operative pain management, patients are most often treated with combinations of non-opioid analgesics, to enhance pain relief and to reduce opioid requirements and opioid-related adverse effects. A diversity of combinations is currently employed in clinical practice, and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti inflammatory drugs (NSAIDs)/COX-2 antagonists, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin reduced 24 h post-operative morphine requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7) mg, 10.9 (9.1, 12.8) mg, and >= 13 mg, respectively, when administered as monotherapy. The opioid-sparing effect of glucocorticoids was less convincing, 2.33 (0.26, 4.39) mg morphine/24 h. Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all seem to have well-documented, clinically relevant analgesic properties. The analgesic effects of glucocorticoids and pregabalin await further clarification. Combination regimens are sparsely documented and should be further investigated in future studies. PMID- 25124341 TI - Comparison of the ocular characteristics of anterior uveitis caused by herpes simplex virus, varicella-zoster virus, and cytomegalovirus. AB - PURPOSE: To compare the clinical characteristics of anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella-zoster virus (VZV), or cytomegalovirus (CMV). METHODS: The medical records were reviewed of 46 patients whose diagnoses were based on their clinical characteristics [e.g., unilateral involvement, presence of keratic precipitates (KPs), and elevation of intraocular pressure (IOP)] and on PCR detection of herpes virus DNA in the aqueous humor. The demographics, chief complaints, and clinical characteristics of the three types of herpetic AU were compared. RESULTS: Of the 46 patients with AU, eight had HSV AU, 20 had VZV-AU, and 18 had CMV-AU. HSV-AU and VZV-AU shared common features, i.e., a relatively acute disease process and the presence of large KPs. Among the three groups of patients, the characteristic features of those with VZV-AU were severe intraocular inflammation, as shown by severe aqueous flare, highest viral load in the aqueous humor, and presence of segmental iris atrophy. In comparison, patients with CMV-AU had the mildest intraocular inflammation, lowest corneal endothelial cell density, and highest IOP. CONCLUSIONS: Although the AU caused by each of the three types of herpes viruses has a number of common features, each disease also has distinct features that should facilitate an accurate diagnosis. PMID- 25124344 TI - [A quantitative approach to sports training-adapted social determinants concerning sport]. AB - OBJECTIVE: Identifying and quantitatively analysing social determinants affecting disabled teenagers' inclusion/exclusion in high-performance sports. METHOD: This was a descriptive cross-sectional study involving 19 12- to 19-year-old athletes suffering physical and sensory disability and 17 staff from the District Institute of Recreation and Sport. Likert-type rating scales were used, based on four analysis categories, i.e. social structure, socio-economic, educational and living condition determinants. RESULTS: Social inequity pervades the national paralympic sports' system. This is because 74 % of individuals only become recognised as sportspeople when they have obtained meritorious results in set competition without appropriate conditions having been previously provided by such paralympic sports institution to enable them to overcome structural and intermediate barriers. CONCLUSIONS: The social structure imposed on district based paralympic sport stigmatises individuals regarding their individual abilities, affects their empowerment and freedom due to the discrimination experienced by disabled teenagers regarding their competitive achievements. PMID- 25124343 TI - Genetics of metabolic syndrome. AB - Metabolic syndrome (MetS) is a cluster of metabolic traits associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. Central obesity and insulin resistance are thought to play key roles in the pathogenesis of the MetS. The MetS has a significant genetic component, and therefore linkage analysis, candidate gene approach, and genome-wide association (GWA) studies have been applied in the search of gene variants for the MetS. A few variants have been identified, located mostly in or near genes regulating lipid metabolism. GWA studies for the individual components of the MetS have reported several loci having pleiotropic effects on multiple MetS-related traits. Genetic studies have provided so far only limited evidence for a common genetic background of the MetS. Epigenetic factors (DNA methylation and histone modification) are likely to play important roles in the pathogenesis of the MetS, and they might mediate the effects of environmental exposures on the risk of the MetS. Further research is needed to clarify the role of genetic variation and epigenetic mechanisms in the development of the MetS. PMID- 25124345 TI - [The association between socioeconomic indicators andadolescents'physical activity and health-related fitness]. AB - OBJECTIVE: This study was aimed at analysing the association between socioeconomic indicators and adolescents' physical activity and health-related fitness. METHODS: The study involved 716 adolescents from both genders whose age ranged from 10 to 18 years-old (46.8% male) who answered a questionnaire for estimating their habitual physical activity, socioeconomic status; two health related physical fitness tests were also performed. The socioeconomic indicators analysed concerned their parents' educational level and the number of bathrooms, TVs, cars, housemaids, refrigerators and freezers in their homes. RESULTS: A positive association was found between paternal education (PR=1.61 (range 1.27 2.10) and 1.41 (1.10-1.83)) and housemaids (PR=1.97 (1.04-3.81) and 1.92 (1.05 3.52)) with recommended physical activity and leisure time physical activity, respectively. The number of cars (PR=1.48: 1.02-2.19) and freezers (PR=1.88: 1.12 3.18) was positively associated with leisure time physical activity and the number of TVs negatively so (PR=0.75: 0.63-0.89). The number of TVs (PR=0.80: 0.67-0.96) and cars (PR=0.70: 0.55-0.89) was negatively associated with cardiorespiratory fitness whilst paternal education (PR=1.17: 1.00-1.37) and the number of bathrooms in the home (PR=1.25: 1.02-1.54) were positively associated with muscular strength. CONCLUSION: Physical activity and health-related physical fitness were associated with socioeconomic status. However, such association depended on the socioeconomic indicator being analysed. Caution should be taken when analysing studies which use different socioeconomic indicators. PMID- 25124346 TI - [Conceptual differences and praxiological implications concerning social determination or social determinants]. AB - The differences between the social determination of health approach adopted by the Latin-American Social Medicine and Collective Health movement and the WHO's social determinants of health approach are not merely conceptual but involve ethical and political considerations. Different notions of causality and risk are implied in the aforementioned approaches and shape how concepts regarding health illness and health inequity are understood and how they may be confronted. This article attempts to clarify the praxiological implications of such approaches and contextualise the approaches' socio-historical construction, address epistemological, methodological and ontological differences and propose some considerations regarding the praxiological implications. PMID- 25124342 TI - Association of the degree of adiposity and duration of obesity with measures of cardiac structure and function: the CARDIA study. AB - OBJECTIVE: Examine whether there are independent influences of a greater degree of adiposity and longer duration of obesity on cardiac structure and function. METHODS: Participants of CARDIA were 18-30 years when they underwent a baseline examination in 1985-86. Seven follow-up examinations were conducted every 2-5 years. RESULTS: Among 2,547 participants who underwent an echocardiogram at the year 25 examination and were not obese at baseline, 34.4 and 35.5% were overall (BMI >= 30 kg m(-2) ) and abdominally obese (waist circumference: men: >102 cm; women: >88 cm) at year 25, respectively. A greater degree of overall and abdominal adiposity at year 25 were each associated with a greater left ventricular (LV) mass (P < 0.001), LV volume (P < 0.001), LV mass-to-volume ratio (P < 0.001), left atrial dimension (P < 0.001), and ejection fraction (P < 0.05) after adjustment for duration of obesity and other risk factors. In contrast, a longer duration of overall obesity was associated with a greater LV mass (P = 0.003) and a trend for a lower ejection fraction (P = 0.07). CONCLUSIONS: A greater degree of adiposity is strongly associated with concentric LV remodeling in midlife, while the cumulative effects of a longer duration of overall obesity during young adulthood contribute to concentric remodeling predominantly by increasing LV mass. PMID- 25124347 TI - [The relationship-based meaning of teenage pregnancy in Bogota regarding the family system]. AB - OBJECTIVES: Ascertaining the meaning of teenage pregnancy for teenagers and their immediate families. METHODOLOGY: This was an analytical, cross-sectional, exploratory, qualitative study. Data was obtained through in-depth interviews with 10 pregnant teenagers and their immediate families, plus a focus group involving another 12 pregnant teenagers. RESULTS: Analysis by category revealed a tenuous limit between adolescents' narrative identity and a lack of such identity and identity based on the concept of family. Pregnancy provokes a series of responses within families, including fear in a pregnant adolescent and her partner, disappointment on the part of the parents, social isolation and eventual acceptance and redefinition of such pregnancy. CONCLUSIONS: Pregnancy can provide the means for an adolescent to redress a deficit in her emotional needs, such condition keeping the family together at the expense of a teenager's emancipation and may represent an intergenerational legacy. PMID- 25124348 TI - [Elderly people's level of participation in social and recreational activities in Barranquilla, Colombia]. AB - OBJECTIVE: Determining elderly people's level of participation in social and recreational activities in Barranquilla, Colombia. METHODS: This was a descriptive cross-sectional study involving 469 elderly people; a basic activities of daily living scale, which had been adapted to the ongoing activities being carried out in the pertinent scenarios, was used for evaluating their level of participation in social and recreational activities. Bivariate analysis was used for estimating the relationship between level of participation and age-range and coexistence, using OR and chi2 tests. RESULTS: The scale categorized 40.9 % of the subjects as having low participation and only 20.2 % as actively and voluntarily participating in the activities being offered. There was an increased risk of non-participation in social and recreational activities regarding adults being over 80 years of age (OR 3.3: (2.2-4.9) 95 % CI) and those living alone (OR 1.75: (1.09-2.82) 95 % CI). CONCLUSION: A clear trend towards less participation was shown as aged increased; this is why social isolation becomes a risk factor for this group of people's quality of life. It is recommended that social networks promoting the elderly's health and quality of life should thus be strengthened. PMID- 25124349 TI - [Public schoolstudents' body composition and motor performance]. AB - OBJECTIVE: Analysing the influence of body composition on female public school students' motor performance. METHODS: This was a cross-sectional study which involved a sample 371 female public school system students aged seven to 16 years old; they were placed ingroup 1 (G1), group 2 (G2) orgroup 3 (G3). Weight and height were measured for evaluating the body mass index (BMI), triceps and subscapular skinfold thickness for assessing the percentage of body fat (%BF).Sit and reach and 20 meters displacement speed tests were also used. RESULTS: Significant differences were found regarding all anthropometric variables considered. It was found that 41.1% of the 371 female students were overweight or obese (66.1 % in G1, 34.5% in G2 and 25.3 % in G3). Regarding % BF, 29.1% of the students had percentages above suitable levels (23.3 % in G1, 23.8 % in G2 and 35.2 % in G3). Significant differences between G1 and G2 and between G2 and G3 were also found in the motor tests regarding the sit and reach test, as well as between G1 and G3 in the speed test. CONCLUSION: Adiposity may have interfered with the students' motor performance, especially regarding the 20 meters' displacement speed test. PMID- 25124350 TI - [Dental caries in young adults regarding saliva's microbiological and physical chemical characteristics]. AB - OBJECTIVE: Determining the relationship between saliva's physicochemical properties, cariogenic microorganism count, facultative anaerobic and gram negative bacteria based on caries' experience in young adults. MATERIALS AND METHODS: Stimulated whole saliva was collected from 120 students aged 17 to 34 years old for analysing salivary flow rate, pH, calcium and phosphate ion concentration, lactic acid, cariogenic microorganism count and facultative and gram-negative bacteria. RESULTS: Salivary flow rate was included in the biological reference interval but was not found to be associated with caries; the same thing happened regarding lactic acid. A direct relationship was found between calcium and phosphate concentration and dental cavities. Streptococcus mutans was associated with white spot lesion whereas Lactobacillus spp., facultative anaerobic and gram-negative bacteria were associated with advanced cavities. CONCLUSIONS: Saliva's physicochemical and microbiological characteristics in the young adult group evaluated here were differentially related to caries in different degrees of progress. PMID- 25124351 TI - [The relationship between the oral health and socioeconomic characteristics of chronic kidney disease patients undergoing haemodialysis treatment or kidney transplant]. AB - OBJECTIVE: Characterising the oral health of patients undergoing different types of dialysis or kidney transplant. MATERIALS AND METHODS: This was a descriptive study which involved multivariate analysis of information taken from an initial database regarding 336 patients; 49 % were receiving haemodialysis, 34 % peritoneal dialysis, 7 % pre-dialysis and 10 % kidney transplant. Illustrative variables were age, gender, marital status, occupation, education, oral hygiene and gingival indexes, flossing, decayed, missing, and filled teeth (DMFT) index, renal disease aetiology and type of dialysis being received. A hierarchical clustering method was used. RESULTS: Four groups of patients were identified. Class 1 (37.8 %) consisted of unmarried men having had secondary education and having good oral hygiene, very high DMFT, with haemodialysis but no stomatological pathology. Class 2 (20.24 %) included haemodialysis patients who had received elementary education, were unemployed, had inadequate oral hygiene, severe gingivitis, very high DMF rate and high Candida frequency. Class 3 (31.2 %) included women undergoing peritoneal dialysis who were over 70 years old, had received elementary education, were housewives, edentulous and who had loss of vertical dimension. Class 4 (10.7 %) included men who had received renal transplant, secondary education and were employees; one third of them were edentulous and had soft tissue alterations. CONCLUSION: Multivariate analysis indicated a possible relationship between the type of dialysis received and patients' socioeconomic characteristics regarding oral health status. PMID- 25124352 TI - Occupational exposure to air pollutants: particulate matter and respiratory symptoms affecting traffic-police in Bogota. AB - OBJECTIVES: Quantifying personal exposure to particles less than 10 micrometres in diameter (PM10) and determining the prevalence of respiratory symptoms in traffic-police officers working in Bogota's metropolitan area. METHODS: This was a cross-sectional study of 574 traffic-police officers divided into two groups (477 traffic-police and 97 police working in an office). They were given a questionnaire inquiring about respiratory symptoms, toxicological medical evaluation, lung function tests and personal PM10 monitoring. The differences between groups were found using stratified analysis (i.e. comparing odds ratios). Multivariate analysis of factors related to symptoms and diagnosis of respiratory alteration was also performed. RESULTS: Respiratory symptoms concerned a higher prevalence of cough, expectoration and rhinosinusitis in the traffic-police group. Medical examination revealed that the traffic-police group had higher nasal irritation prevalence; lung function tests showed no difference. Mean PM10 levels were higher for the traffic-police group (139.4 MUg/m3), compared to the office work group (86.03 MUg/m3). DISCUSSION: PM10 values in both groups did not exceed allowable limits for respirable particles in the workplace according to ACGIH standards. Traffic-police exposed to air pollution had an increased risk of developing respiratory symptoms and signs, thereby agreeing with the results of this and other studies. Personal monitoring is a valuable tool when quantifying the concentration of PM10to which an individual has been exposed during a normal workday. This study contributes towards further research in to the effects of PM10 in populations at risk. PMID- 25124353 TI - [Population exposure to mercury in the municipality of San Marcos (Sucre department) due to eating contaminated rice (Oryza sativa)]. AB - OBJECTIVE: Determining the magnitude of mercury exposure in the population living in the municipality of San Marcos due to eating contaminate drice (Oryza sativa). METHODS: Twenty people (representative of the population) were selected, as were food (raw rice) and hair samples for determining total mercury and methyl mercury by cold vapour atomic absorption spectrophotometry. Student's t-test was used for comparing different samples (p<0.05 significance level) and correlation was analysed for determining the relationship between consumption habits and mercury concentration in humans. RESULTS: Rice sold loose (i.e. unpackaged San Marcos white rice) was the only sample having 0.021 mg/g minimum total mercury concentration, whilst rice sold in packaged form yielded no measurable value. Only 5% of the population sample exceeded the US Environmental Protection Agency's (EPA) 0.1 mg/kg bw/day reference dose (RfD) for Me Hg ingestion (RfD). CONCLUSIONS: The HgT exposure of people living in and around San Marcos concerning rice consumption was low and did not involve great risks to their health. However, frequent consumption of other types of contaminated food could pose a potential threat to the consumers' health, meaning that ongoing environmental monitoring is necessary. PMID- 25124354 TI - [Central venous catheter-related complications in critically ill children]. AB - OBJECTIVE: Placing central venous catheters is essential when managing critically ill children. This paper was thus aimed at identifying the major complications involved in this and determining the incidence of mechanical and infection related complications associated with central venous catheterization in critically ill children. MATERIAL AND METHODS: A descriptive study was undertaken between October 2011 and March 2012 of all new central venous catheters inserted in critically ill children. The definition of central venous catheter infection was based on CDC criteria. RESULTS: During the study period 200 central venous catheters were placed, 51 % in male patients, mostly infants; 71 % required mechanical ventilation and 56.5 % medication for hemodynamic support. Respiratory tract infections were the leading diagnosis on admission in 33 % of the cases. Complications were reported in 8.5 % of the children (52 % of these being due to mechanical complication and 48 % to infection). Mechanical complication incidence was 4.5% and eight central venous catheters fulfilled CDC criteria for central line associated blood stream infection (4 % incidence, i.e. 5 per 1,000 catheter/day rate). CONCLUSIONS: Despite some complications arising from its use, central venous catheter placement is a safe procedure. Mechanical and infection incidence associated with central venous catheter placement should be known, not only because it differs from that regarding adult patients but also because this can help to establish preventative measures for reducing such complications and improving the care of critically ill children. PMID- 25124355 TI - [HIV/AIDS prevalence in Medellin and presumptive test diagnostic accuracy (2006 2012)]. AB - OBJECTIVE: Determining HIV/AIDS prevalence in Medellin, Colombia, and its association with demographic factors2006-2012,as well as exploring screening test performance. METHODS: This was a cross-sectional study involving 5,851subjects. Descriptive statistics were used to describe the population (i.e. frequencies and summary measures); infection prevalence was calculated and its association with demographic factors identified by using parametric and non-parametric statistical tests, prevalence ratios and odds ratios. Predictive values were calculated, as were the percentage of false results and percentage of subjects correctly diagnosed. RESULTS: Mean age was 27 years old (0 to 94 year range); 70.5% of the population were female. HIV/AIDS prevalence was found to be 1.8% during the study period (0.32% annually). A statistical association was found with gender and age, a higher prevalence being found in males and adults. The false positive rate was 0.7%, negative predictive value100%, positive predictive value 71% and there was 99% overall efficiency. CONCLUSION: HIV/AIDS prevalence found in this study was significantly higher than that found in other studies in the Antioquia department and for Colombia overall. The male and female infection prevalence ratio revealed increased diagnosis in women. The screening test performed well in areas having less than 1% infection prevalence. PMID- 25124356 TI - [Mathematical modelling of an infectious disease in a prison setting and optimal preventative control strategies]. AB - A mathematical model was constructed for modelling transmission dynamics and the evolution of an infectious disease in a prison setting, considering asymptomatic infectious people, symptomatic infectious people and isolated infectious people. The model was proposed as a nonlinear differential equation system for describing disease epidemiology. The model's stability was analysed for including a preventative control strategy which would enable finding a suitable basic reproduction number-based control protocol. A cost function related to the system of differential equations was formulated to minimise infectious populations and intervention costs; such function was minimised by using the Pontryagin maximum principle which determines optimum preventative control strategies by minimising both infectious populations and associated costs. A numerical analysis of the model was made, considering preventative control effectiveness levels and different control weighting constants. Conclusions were drawn. The basic reproduction number characterises system stability and leads to determining clear control criteria; a preventative control threshold was defined, based on the controlled basic reproduction number which enabled deducing that disease control requires uniform preventative control involving high rates of effectiveness. PMID- 25124357 TI - Iron speciation in beans (Phaseolus vulgaris) biofortified by common breeding. AB - The iron storage protein ferritin is a potential vehicle to enhance the iron content of biofortified crops. With the aim of evaluating the potential of ferritin iron in plant breeding, we used species-specific isotope dilution mass spectrometry to quantify ferritin iron in bean varieties with a wide range of total iron content. Zinc, phytic acid, and polyphenols were also measured. Total iron concentration in 21 bean varieties ranged from 32 to 115 ppm and was positively correlated with concentrations of zinc (P = 0.001) and nonferritin bound iron (P < 0.001). Ferritin iron ranged from 13% to 35% of total iron and increased only slightly in high iron beans (P = 0.007). Concentrations of nonferritin bound iron and phytic acid were correlated (P = 0.001), although phytic acid:iron molar ratio decreased with increasing iron concentration (P = 0.003). Most iron in high iron beans was present as nonferritin bound iron, which confirms our earlier finding showing that ferritin iron in beans was lower than previously published. As the range of ferritin iron content in beans is relatively narrow, there is less opportunity for breeders to breed for high ferritin. The relevance of these findings to the extent of iron absorption depends on resolving the question of whether ferritin iron is absorbed or not to a greater extent than nonferritin bound iron. PMID- 25124358 TI - Comparatively examining of the apelin-13 levels in the Capoeta trutta (Heckel, 1843) and Cyprinus carpio (Linnaeus, 1758). AB - Apelin is a recently discovered peptide produced by several tissues in the various vertebrates and fish. Apelin has been suggested to have role in regulation of many diverse physiological functions including food intake, energy homoeostasis, immunity, osmoregulation and reproduction. In this study, apelin-13 levels in the blood serum of Cyprinus carpio and Capoetta trutta were determined. Then the results were compared between two species and sexes of each species. Apelin-13 level was analysed using the enzyme-linked immunoassay (ELISA) kit (Rat apelin-13 ELISA kit, catalog no: CSB-E14367r). Apelin-13 level in the blood serum of C. trutta was significantly higher than those of the C. carpio (p < 0.05). However, its levels were observed to be no significant difference (p > 0.05) that compared to between sexes of each species. There was a significant negative correlation (r = -0.829, p = 0.0001) between the apelin-13 level and body weight of C. carpio. However, no significant correlation (r = -0.022, p = 0.924) between the apelin-13 level and weight of C. trutta observed. PMID- 25124360 TI - Antiplatelet therapy before, during, and after extremity revascularization. AB - Peripheral arterial disease (PAD) is well recognized as a marker for systemic atherosclerosis. Platelets play an essential role in all stages of the disease, contributing to both thrombosis and the development of atherosclerosis. Medication regimens to optimize outcomes in both patients who are to undergo revascularization and those who will be managed without interventional therapy must address antiplatelet therapy. Given the common cardiovascular and cerebrovascular comorbidities in patients with PAD, antiplatelet therapy has the potential to decrease thromboembolic events in addition to improving patency after interventions. This clinical update reviews the current literature and recommendations for antiplatelet therapy in patients with PAD. PMID- 25124359 TI - Preoperative dietary restriction reduces intimal hyperplasia and protects from ischemia-reperfusion injury. AB - OBJECTIVE: Whereas chronic overnutrition is a risk factor for surgical complications, long-term dietary restriction (reduced food intake without malnutrition) protects in preclinical models of surgical stress. Building on the emerging concept that acute preoperative dietary perturbations can affect the body's response to surgical stress, we hypothesized that short-term high-fat diet (HFD) feeding before surgery is detrimental, whereas short-term nutrient/energy restriction before surgery can reverse negative outcomes. We tested this hypothesis in two distinct murine models of vascular surgical injury, ischemia reperfusion (IR) and intimal hyperplasia (IH). METHODS: Short-term overnutrition was achieved by feeding mice a HFD consisting of 60% calories from fat for 2 weeks. Short-term dietary restriction consisted of either 1 week of restricted access to a protein-free diet (protein/energy restriction) or 3 days of water only fasting immediately before surgery; after surgery, all mice were given ad libitum access to a complete diet. To assess the impact of preoperative nutrition on surgical outcome, mice were challenged in one of two fundamentally distinct surgical injury models: IR injury to either kidney or liver, or a carotid focal stenosis model of IH. RESULTS: Three days of fasting or 1 week of preoperative protein/energy restriction attenuated IH development measured 28 days after focal carotid stenosis. One week of preoperative protein/energy restriction also reduced plasma urea, creatinine, and damage to the corticomedullary junction after renal IR and decreased aspartate transaminase, alanine transaminase, and hemorrhagic necrosis after hepatic IR. However, exposure to a HFD for 2 weeks before surgery had no significant impact on kidney or hepatic function after IR or IH after focal carotid stenosis. CONCLUSIONS: Short-term dietary restriction immediately before surgery significantly attenuated the vascular wall hyperplastic response and improved IR outcome. The findings suggest plasticity in the body's response to these vascular surgical injuries that can be manipulated by novel yet practical preoperative dietary interventions. PMID- 25124361 TI - Standard endovascular treatment of abdominal aortic aneurysms in patients with very short proximal necks using the Endurant stent graft. AB - OBJECTIVE: This study evaluated and compared the midterm results of endovascular aortic aneurysm repair with the Endurant (Medtronic Inc, Santa Rosa, Calif) stent graft system in off-label use in patients with short (<10 mm) proximal aortic necks and in patients treated according to device-specific instructions for use. METHODS: This was a case-control (2:1) single-center retrospective analysis of prospectively collected data performed between September 2008 and December 2012. Analysis identified 19 elective patients with short (<10 mm) proximal necks and mild angulations (<=45 degrees ) treated with the Endurant stent graft and 38 patients matched for age, sex, and aneurysm diameter with proximal aortic necks >=10 mm in length who met the instructions for use. End points included technical and clinical success and freedom from any secondary intervention, any type of endoleak, and aneurysm-related death. RESULTS: The short-neck group was a mean +/ standard deviation age of 71.7 +/- 8.9 years, 84% were men, and their mean infrarenal aortic neck length was 6.1 +/- 1.2 mm. Mean suprarenal and infrarenal angles were 110 degrees +/- 10.4 degrees and 170 degrees +/- 15.4 degrees , respectively. Aortic neck diameters were similar between the groups (26.6 +/- 3.8 vs 25.7 +/- 3.7 mm; P = .36). Primary technical success was achieved in all cases. Off-label patients were more likely to require additional proximal cuff deployment to successfully obtain a seal (21% vs 3%; P = .04). The two patient groups were similar in rates of perioperative mortality, morbidity, and complications. Mean follow-up of 24 +/- 12 months revealed no differences in clinical success, freedom from reintervention, and aneurysm-related death. No type I endoleaks were observed in either group during the follow-up period. CONCLUSIONS: The Endurant stent graft system applied off-label in patients with very short aneurysm necks (<10 mm) with mild angulation showed acceptable treatment results. These midterm results might suggest its use in carefully selected patients with very short neck anatomy. Long-term data are needed to verify the observed durability of the Endurant stent graft. PMID- 25124362 TI - Glucose-lowering effect of insulin degludec is independent of subcutaneous injection region. AB - BACKGROUND AND OBJECTIVES: Patients with diabetes mellitus inject insulin in different regions of the body. This study investigated the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a new-generation once daily basal insulin with an ultra-long duration of action, after subcutaneous (SC) administration in different injection regions. METHODS: In this study, 20 healthy subjects received single SC doses of IDeg (0.4 U/kg; separated by 13-21 days) in the thigh, abdomen and deltoid in a randomised, open-label, single centre, single-dose, complete crossover trial. Each dose was followed by a 24-h euglycaemic clamp and 120-h pharmacokinetic blood sampling. The obtained pharmacokinetic/pharmacodynamic profiles were extrapolated to steady state by simulation using a pharmacokinetic/pharmacodynamic model. RESULTS: Total IDeg exposure [area under the IDeg serum concentration-time curve 0-120 h after a single dose (AUCIDeg,0-120h,SD)] and maximum serum concentration [maximum IDeg serum concentration after a single dose (C max,IDeg,SD)] were higher (6-7 and 23 27 %, respectively) following a single SC dose in the deltoid or abdomen, compared with the thigh, as also observed with other insulin preparations. No statistical difference was observed in these measures between deltoid and abdominal administration. No pronounced differences were observed in the glucose lowering effect of IDeg [area under the glucose infusion rate (GIR) curve 0-24 h after a single dose (AUCGIR,0-24h,SD) and maximum GIR after a single dose (GIRmax,SD)] when injected in the thigh, abdomen or deltoid (AUCGIR,0-24h,SD 2,572, 2,833 and 2,960 mg/kg, respectively). Simulated mean steady-state pharmacokinetic and pharmacodynamic profiles supported a flat and stable IDeg exposure and effect regardless of injection region, with comparable total glucose lowering effects [area under the GIR curve at steady state (AUCGIR,tau,SS)] between the thigh, abdomen and deltoid. CONCLUSIONS: These findings support administering IDeg SC in the thigh, upper arm or abdominal wall without affecting IDeg absorption or effect at steady state. PMID- 25124364 TI - [How can we improve the care of patients with benign anorectal diseases?]. PMID- 25124363 TI - Cross-platform comparison of nucleic acid hybridization: toward quantitative reference standards. AB - Measuring interactions between biological molecules is vitally important to both basic and applied research as well as development of pharmaceuticals. Although a wide and growing range of techniques is available to measure various kinetic and thermodynamic properties of interacting biomolecules, it can be difficult to compare data across techniques of different laboratories and personnel or even across different instruments using the same technique. Here we evaluate relevant biological interactions based on complementary DNA and RNA oligonucleotides that could be used as reference standards for many experimental systems. We measured thermodynamics of duplex formation using isothermal titration calorimetry, differential scanning calorimetry, and ultraviolet-visible (UV-vis) monitored denaturation/renaturation. These standards can be used to validate results, compare data from disparate techniques, act as a teaching tool for laboratory classes, or potentially to calibrate instruments. The RNA and DNA standards have many attractive features, including low cost, high purity, easily measurable concentrations, and minimal handling concerns, making them ideal for use as a reference material. PMID- 25124366 TI - Properties of starch from potatoes differing in glycemic index. AB - Potatoes are a popular source of dietary carbohydrate worldwide and are generally considered to be a high glycemic index (GI) food. Potato starch characteristics play a key role in determining their rate of digestion and resulting glycemic response. Starches isolated from seven potato cultivars with different GI values, including a low GI cultivar (Carisma), were examined for relative crystallinity, granule size distribution, amylopectin chain length, and thermal and pasting properties. Starch from the Carisma cultivar was more thermally stable and more resistant to gelatinization, with significantly higher (p < 0.05) pasting temperature and differential scanning calorimetry (DSC) gelatinization onset, peak and conclusion temperatures, compared to the other cultivars. Differences between the potatoes in the other properties measured did not align with the GI ranking. Thermal analysis and starch pasting properties may be useful indicators for preliminary identification of potato cultivars that are digested slowly and have a lower GI. PMID- 25124365 TI - How immigrants adapt their smoking behaviour: comparative analysis among Turkish immigrants in Germany and the Netherlands. AB - BACKGROUND: Smoking behaviour among immigrants is assumed to converge to that of the host country's majority population with increasing duration of stay. We compared smoking prevalence among Turkish immigrants residing in two different countries (Germany (DE)/the Netherlands (NL)) between and within countries by time spent in Turkey and DE/NL. METHODS: The German 2009 micro-census and the Dutch POLS database (national survey, 1997-2004) were analysed. An interaction variable with dichotomised length of stay (LOS) in Turkey (age: 0-17; 18+) and categorised LOS in the host country (immigration year: 1979 and earlier, 1980 1999, 2000-2009; the latter only for Germany) was generated. Age standardised smoking prevalences and sex-specific logistic regression models were calculated. RESULTS: 6,517 Turkish participants were identified in Germany, 2,106 in the Netherlands. Age-standardised smoking prevalences were higher among Turkish immigrants in the Netherlands compared to those in Germany: 62.3% vs. 53.1% (men/lower education); 30.6% vs. 23.0% (women/lower education). A similar trend was observed for the majority population of both countries. The chance of being a smoker was lower among Turkish men with short LOS in Turkey and middle LOS in Germany/the Netherlands compared to those with short LOS in Turkey and long LOS in Germany/the Netherlands (NL: OR = 0.57[95% CI = 0.36-0.89]; DE: OR = 0.73[95% CI = 0.56-0.95]). Contrary to that, the chance of being a smoker was higher among Turkish men with long LOS in Turkey and middle LOS in Germany/the Netherlands compared to those with long LOS in Turkey and long LOS in Germany/the Netherlands (NL: OR = 1.35[95% CI = 0.79-2.33]; DE: OR = 1.44[95% CI = 1.03-2.02]). The effects for Turkish women were similar, but smaller and often non-significant. CONCLUSION: Turkish immigrants adapt their smoking behaviour towards that of the Dutch/German majority population with increasing duration of stay. This was particularly obvious among those who left Turkey before the age of 18 years - a group that needs tailored interventions to prevent further increases in smoking. Those who left Turkey as adults and spent a short time in the host countries show 'imported' smoking patterns. A limitation of this study is the use of cross sectional data: a cohort effect cannot be ruled out. Our findings have to be confirmed with longitudinal data. PMID- 25124368 TI - On selection for flowering time plasticity in response to density. AB - Different genotypes often exhibit opposite plastic responses in the timing of the onset of flowering with increasing plant density. In experimental studies, selection for accelerated flowering is generally found. By contrast, game theoretical studies predict that there should be selection for delayed flowering when competition increases. Combining different optimality criteria, the conditions under which accelerated or delayed flowering in response to density would be selected for are analysed with a logistic growth simulation model. To maximize seed production at the whole-stand level (simple optimization), selection should lead to accelerated flowering at high plant density, unless very short growing seasons select for similar onset of flowering at all densities. By contrast, selection of relative individual fitness will lead to delayed flowering when season length is long and/or growth rates are high. These different results give a potential explanation for the observed differences in direction of the plastic responses within and between species, including homeostasis, as a result of the effect of the variation in season length on the benefits of delayed flowering. This suggests that limited plasticity can evolve without the costs and limits that are currently thought to constrain the evolution of plasticity. PMID- 25124367 TI - Improvement of arterial oxygenation in free-ranging moose (Alces alces) immobilized with etorphine-acepromazine-xylazine. AB - BACKGROUND: The effect of intranasal oxygen and/or early reversal of xylazine with atipamezole on arterial oxygenation in free-ranging moose (Alces alces) immobilized with etorphine-acepromazine-xylazine with a cross-sectional clinical study on 33 adult moose was evaluated. RESULTS: Before treatment the mean+/-SD (range) partial pressure of arterial oxygen (PaO2) was 62+/-17 (26-99) mmHg. Twenty-six animals had a PaO2<80 mmHg. Ten had a PaO2 of 40-60 mmHg and three animals had a PaO2<40 mmHg. Intranasal oxygen and intravenous administration of atipamezole significantly increased the mean PaO2, as did the combination of the two. In contrast, atipamezole administered intramuscularly at the evaluated dose had no significant effect on arterial oxygenation. CONCLUSIONS: This study shows that intranasal oxygen effectively improved arterial oxygenation in immobilized moose, and that early intravenous reversal of the sedative component, in this case xylazine, in an opioid-based immobilization drug-protocol significantly improves arterial oxygenation. PMID- 25124369 TI - Limitations of beta-lactam therapy for infections caused by susceptible Gram positive bacteria. AB - Penicillin and related beta-lactam agents have been the most widely used and most important antimicrobials in medical history, and remain the recommended therapy for many infectious diseases 85 years after the discovery of penicillin by Alexander Fleming. Yet the efficacy of these agents has been undermined by two factors - the emergence of clinically significant resistance to the antimicrobial activity of these agents, and clinical situations in which these drugs may be suboptimal (even though the bacterial pathogens are not "resistant" to the drugs). Observations in experimental infection models in animals (group A streptococcal myositis, pneumococcal meningitis and pneumonia, group B streptococcal sepsis) and in some cases clinical studies suggest that monotherapy with beta-lactam antibiotics may be inferior to treatment with other types of antibiotics, alone or in combination with beta-lactams - even in situations where the bacterial pathogens remain fully "susceptible" to beta-lactams in vitro. PMID- 25124371 TI - Monocytes and Parkinson's disease: invaders from outside? PMID- 25124372 TI - Reengagement of high-need individuals with serious mental illness after discontinuation of services. AB - OBJECTIVE: The study determined rates of reengagement in services for individuals with serious mental illness who had discontinued services. METHODS: As part of a quality assurance program in New York City involving continuous review of Medicaid claims and other administrative data, clinician care monitors identified 2,834 individuals with serious mental illness who were apparently in need of care but disengaged from services. The care monitors reviewed monthly updates of Medicaid claims, encouraged outreach from providers who had previously worked with identified individuals, and determined whether individuals had reengaged in services. RESULTS: Reengagement rates over a 12-month follow-up period were low, particularly for individuals who had been incarcerated or for whom no service provider was available to provide outreach. CONCLUSIONS: Subgroups of disengaged individuals with serious mental illness have different rates of reengagement. Active outreach by providers might benefit some, but such targeting is inefficient when the individual cannot be located. PMID- 25124373 TI - Combined use of NGF/BDNF/bFGF promotes proliferation and differentiation of neural stem cells in vitro. AB - Neurotrophic factors can promote the proliferation and differentiation of neural stem cells (NSCs). Here we report that the possibility of using bFGF in combination with BDNF and NGF to promote proliferation and differentiation of NSCs in vitro. C57BL/6 mouse NSCs were cultured, passaged and stained by immunofluorescence for nestin and GFP. According to different neurotrophic factors added to NSCs, seven experiment groups (NGF, BDNF, bFGF, bFGF+NGF, bFGF+BDNF, NGF+BDNF and NGF+BDNF+bFGF) and a blank control group were established. One week after induction and differentiation, results showed that there was significant difference in the percentage of NSCs differentiating into neurons among the experiment groups. The percentage in the multi-factor groups was significantly higher than that in the single-factor groups (p<0.05), among which the percentage was the highest in NGF+BDNF+bFGF group. In the two-factor groups, the percentage in bFGF+NGF and bFGF+BDNF groups was significantly higher than that in NGF+BDNF group (p<0.05). The NSCs growth curves showed that cells proliferated continuously with the time of culture prolonging, but there was significant difference between the group containing bFGF and that without bFGF. Our results demonstrate that combined use of NGF/BDNF/bFGF significantly improved the ability of NSCs proliferation and differentiation. PMID- 25124374 TI - Developmental and degenerative modulation of brain-derived neurotrophic factor transcript variants in the mouse hippocampus. AB - Brain-derived neurotrophic factor (BDNF) is regarded as an important factor for neurogenesis, synaptic plasticity, and neuronal network organization in brain circuits. However, little is known about the regulation of BDNF transcript variants in the hippocampus during postnatal development and following chemically induced neurotoxicity. In the present study, we examined the expression of individual BDNF transcript variants in the mouse hippocampus on postnatal day (PD) 3, 7, 14, 21, and 56, as well as in the adult hippocampus 1, 2, 4, and 8 days after trimethyltin (TMT) treatment. During postnatal development, the expression levels of common BDNF-coding transcripts and BDNF transcript variants increased gradually in the hippocampus, but the temporal patterns of each exon transcript showed significant differences. In the TMT-treated hippocampus, the levels of common BDNF-coding transcripts and exon I, IIC, III, VII, VIII, and IXA transcripts were significantly increased 1 day post-treatment. These observations suggest that the differential regulation of BDNF exon transcripts may be associated with neuronal and synaptic maturation during postnatal development, and neuronal survival and synaptic plasticity in chemically induced neurodegeneration. PMID- 25124375 TI - Aminoglycoside-induced nephrotoxicity--a focus on monitoring: a review of literature. AB - The use of aminoglycoside (AG) antibiotics has declined over the past 15 years primarily due to comparable potency of other antimicrobials and the nephrotoxicity potential of AG drugs. However, resurgence in the use of AG antimicrobials is occurring due to multidrug-resistant gram-negative nosocomial infections. Multidrug-resistant Pseudomonas and Acinetobacter isolates as well as extended-spectrum beta-lactamase-producing Enterobacteriaceae continue to force clinicians to consider AG therapy for nosocomial infections in hospitalized patients and enterococcal endocarditis. Additionally, AGs are still indicated in the treatment of pulmonary exacerbations of cystic fibrosis. Along with the use of AG antibiotics is the associated renal insufficiency complication. This review discusses the mechanism for AG-induced nephrotoxicity. Patient- and drug-related risk factors are discussed to help identify patients at increased risk. The issue of serum-level monitoring is discussed relative to the development of nephrotoxicity. PMID- 25124377 TI - A Retrospective Evaluation of Response to Vitamin D Supplementation in Obese Versus Nonobese Patients. AB - OBJECTIVE: To evaluate the impact of body mass index (BMI) on vitamin D status following ergocalciferol therapy. METHODS: A retrospective evaluation of patients aged 18 years and older with a baseline serum 25(OH)D < 30 ng/mL who received prescription ergocalciferol 50 000 IU at any dose between July 2009 and November 2011 was conducted. Patients were included if pre- and posttreatment 25(OH)D levels were available within 3 months of therapy. RESULTS: Two hundred and thirteen patients were included in the study with 52% having a BMI >=30 kg/m(2). Thirty-eight different ergocalciferol regimens were prescribed, and the majority of patients (66.2%) received a regimen consisting of 50 000 IU once weekly for variable durations. Mean 25(OH)D levels increased from 18.8 +/- 6.6 ng/mL at baseline to 35.0 +/- 13.8 ng/mL with 61.0% (n = 130) of patients having attained vitamin D sufficiency, 25(OH)D >= 30 ng/mL, with their prescribed ergocalciferol regimen. Obese patients with a BMI >=30 were less likely to attain vitamin D sufficiency following replacement than patients with a BMI <30 kg/m(2) (52% vs 71%; P = .0161). CONCLUSION: Our study demonstrated an overall moderate response rate to replacement therapy with ergocalciferol and considerable variability in vitamin D replacement strategies initiated by primary care providers. Based on our findings, elevated BMI >=30 kg/m(2) may impact the likelihood of attaining vitamin D sufficiency with ergocalciferol. PMID- 25124376 TI - Stress, Drugs, and Alcohol Use Among Health Care Professional Students: A Focus on Prescription Stimulants. AB - OBJECTIVE: To contrast the characteristics of pharmacy, medicine, and physician assistant (PA) students regarding the prevalence of drug, alcohol, and tobacco use and to identify risk factors associated with prescription stimulant use. PARTICIPANTS: Five hundred eighty nine students were recruited to complete a 50 item Web-based survey. MAIN OUTCOME MEASURES: Demographics, nonmedical prescription medication use, illicit drug and alcohol use, Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR) psychiatric diagnoses, and perceived stress scale (PSS) scores. RESULTS: Medicine and PA students reported greater nonmedical prescription stimulant use than pharmacy students (10.4% vs 14.0% vs 6.1%; P < .05). Medicine and PA students were more likely to report a history of an anxiety disorder (12.1% vs 18.6% vs 5.9%; P < .05), major depressive disorder (9.4% vs 8.1% vs 3.3%; P < .05), and attention-deficit hyperactivity disorder (ADHD; 4.0% vs 9.3% vs 0.7%; P < .001) than pharmacy students. PSS scores for all 3 groups (21.9-22.3) were roughly twice as high as the general adult population. CONCLUSION: Illicit drug and prescription stimulant use, psychiatric disorders, and elevated stress levels are prevalent among health care professional students. Health care professional programs may wish to use this information to better understand their student population which may lead to a reassessment of student resources and awareness/prevention programs. PMID- 25124378 TI - Angioedema related to Angiotensin inhibitors. AB - Angiotensin inhibitors have been extensively evaluated in clinical trials and have demonstrated significant reductions in morbidity and mortality following myocardial infarction and stroke, as well as in patients with heart failure or who are at risk of cardiovascular disease. Further, both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are frequently prescribed for the treatment of hypertension and to preserve renal function in patients with diabetes mellitus and chronic kidney disease. Angioedema is a known, but rare, adverse effect of ACEIs and ARBs. Therefore, it is important for clinicians to have a thorough understanding of risks and benefits of prescribing these medications, particularly in patients with a history of angioedema. This review describes the literature evaluating the incidence and cross-reactivity of angioedema with ACEIs and ARBs in order to provide guidance for clinical decision making. PMID- 25124380 TI - Beta-lactam hypersensitivity and cross-reactivity. AB - Penicillin is the most frequently reported cause of drug allergy, and cross reactivity of penicillins with other beta-lactam antibiotics is an area of debate. This review evaluates the available data on immunoglobulin E-mediated penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem, and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October 2013, and selected references from review articles were also evaluated. There is a wide variety in reported incidences of cross-reactivity between penicillins and cephalosporins or carbapenems, with early retrospective studies suggesting up to 41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam antibiotics is frequently employed in the case of a penicillin allergy, as prescribers believe that there is no cross-reactivity between the 2 drug classes. More recent prospective studies suggest that the rates of cross-reactivity with cephalosporins and carbapenems are <5% and <1%, respectively. Similarities in penicillin and cephalosporin side chains may play a role in cross-reactivity between these classes. Cross-reactivity with monobactams is essentially negligible; however, there are some clinical data to support an interaction between ceftazidime and aztreonam, due to the similarity of their side chains. The data reviewed suggest that avoidance of other beta-lactams in patients with type 1 hypersensitivity to penicillins should be reconsidered. PMID- 25124379 TI - Nonchemotherapy drug-induced neutropenia and agranulocytosis: could medications be the culprit? AB - Drug-induced agranulocytosis is a severe complication that has been implicated with most classes of medications. Medications such as clozapine, trimethoprim sulfamethoxazole and methimazole have been more commonly associated with agranulocytosis than other agents. Although the pathogenesis isn't fully elucidated, it appears to be two-fold with a direct toxicity to the myeloid cell line and immune-mediated destruction. Patients may be asymptomatic at the time neutropenia is discovered or may present with more severe complications such as sepsis. In approximately 5% of cases drug-induced agranulocytosis may be fatal. Management of drug-induced agranulocytosis includes the immediate discontinuation of the offending medication, initiation of broad-spectrum antibiotics and consideration of the use of granulocyte colony-stimulating factors in high-risk patients. PMID- 25124381 TI - Links between patterns of racial socialization and discrimination experiences and psychological adjustment: a cluster analysis. AB - This study used a person-oriented analytic approach to identify meaningful patterns of barriers-focused racial socialization and perceived racial discrimination experiences in a sample of 295 late adolescents. Using cluster analysis, three distinct groups were identified: Low Barrier Socialization-Low Discrimination, High Barrier Socialization-Low Discrimination, and High Barrier Socialization-High Discrimination clusters. These groups were substantively unique in terms of the frequency of racial socialization messages about bias preparation and out-group mistrust its members received and their actual perceived discrimination experiences. Further, individuals in the High Barrier Socialization-High Discrimination cluster reported significantly higher depressive symptoms than those in the Low Barrier Socialization-Low Discrimination and High Barrier Socialization-Low Discrimination clusters. However, no differences in adjustment were observed between the Low Barrier Socialization-Low Discrimination and High Barrier Socialization-Low Discrimination clusters. Overall, the findings highlight important individual differences in how young people of color experience their race and how these differences have significant implications on psychological adjustment. PMID- 25124382 TI - Methylenetetrahydrofolate reductase C667T polymorphism is associated with increased risk of coronary artery disease in a Chinese population. AB - Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) rs1801133 C/T, matrix metalloproteinases (MMPs)-2, tumour necrosis factor (TNF)-alpha, macrophage migration inhibitory factor (MIF) rs755622 G/C and cyclin D1 (CCND1) rs678653 G/C contribute to CAD susceptibility. We examined the association between the five polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF MS). When the MTHFR rs1801133 CC homozygote genotype was used as the reference group, the TT or CT/TT genotypes were associated with a significantly increased risk for CAD. The CT heterozygote genotype was not associated with the risk for CAD. Logistic regression analyses revealed that MMP-2 rs243865 C/T, TNF-alpha rs1800629 A/G, MIF rs755622 G/C and CCND1 rs678653 G/C polymorphisms were not associated with the risk of CAD. These findings suggest that the MTHFR rs1801133 C/T polymorphism is associated with CAD development. Future larger studies with other ethnic populations are required to confirm current findings. PMID- 25124383 TI - Protective effect of chemically modified SOD on lipid peroxidation and antioxidant status in diabetic rats. AB - Reactive oxygen species mediated oxidative stress play an important role on the injury of tissue damage and increased attention has been focused on the role of free radicals in diabetes mellitus (DM). In the present study firstly superoxide dismutase (SOD) enzyme was chemically modified with two different polymer and physicochemical properties of these conjugates clearly analyzed. Then, the stability of carboxymethylcellulose-SOD (CMC-SOD) and poly methyl vinyl ether-co maleic anhydride-SOD (PMVE/MA-SOD) conjugates was investigated against temperature and externally added H2O2. Moreover, we investigated the effect of chemically modified SOD enzyme on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetic rats. PMVE/MA-SOD conjugate treatment significantly reduced MDA level compared with the control groups, native and CMC SOD conjugate treated groups in brain, kidney and liver tissue. GSH and SOD enzyme activity in diabetic groups was significantly increased by treatment of CMC-SOD and PMVE/MA-SOD conjugates. The protective effects on degenerative changes in diabetic rats were also further confirmed by histopathological examination. This study provides the preventative activity of SOD-polymer conjugates against complication of oxidative stress in experimentally induced diabetic rats. These results suggest that chemically modified SOD is effective on the oxidative stress-associated disease and offer a therapeutic advantage in clinical use. PMID- 25124384 TI - Template-free synthesis and mechanistic study of porous three-dimensional hierarchical uranium-containing and uranium oxide microspheres. AB - A novel type of uranium-containing microspheres with an urchin-like hierarchical nano/microstructure has been successfully synthesized by a facile template-free hydrothermal method with uranyl nitrate hexahydrate, urea, and glycerol as the uranium source, precipitating agent, and shape-controlling agent, respectively. The as-synthesized microspheres were usually a few micrometers in size and porous inside, and their shells were composed of nanoscale rod-shaped crystals. The growth mechanism of the hydrothermal reaction was studied, revealing that temperature, ratios of reactants, solution pH, and reaction time were all critical for the growth. The mechanism study also revealed that an intermediate compound of 3 UO3 ?NH3 ?5 H2 O was first formed and then gradually converted into the final hydrothermal product. These uranium-containing microspheres were excellent precursors to synthesize porous uranium oxide microspheres. With a suitable calcination temperature, very uniform microspheres of uranium oxides (UO2+x , U3 O8 , and UO3 ) were successfully synthesized. PMID- 25124386 TI - The mobile phone compatible burns dressing. PMID- 25124385 TI - Withdrawal of antiepileptic drugs in glioma patients after long-term seizure freedom: design of a prospective observational study. AB - BACKGROUND: Epilepsy is common in patients with a glioma. Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment, but may cause side effects and may negatively impact neurocognitive functioning and quality of life. Besides antiepileptic drugs, anti-tumour treatment, which currently consists of surgery, radiotherapy and/or chemotherapy, may contribute to seizure control as well. In glioma patients with seizure freedom after anti-tumour therapy the question emerges whether AEDs should be continued, particularly in the case where anti tumour treatment has been successful. We propose to explore the possibility of AED withdrawal in glioma patients with long-term seizure freedom after anti tumour therapy and without signs of tumour progression. METHODS/DESIGN: We initiate a prospective, observational study exploring the decision-making process on the withdrawal or continuation of AEDs in low-grade and anaplastic glioma patients with stable disease and prolonged seizure freedom after anti-tumour treatment, and the effects of AED withdrawal or continuation on seizure freedom. We recruit participants through the outpatient clinics of three tertiary referral centers for brain tumour patients in The Netherlands. The patient and the treating physician make a shared decision to either withdraw or continue AED treatment. Over a one-year period, we aim to include 100 glioma patients. We expect approximately half of the participants to be willing to withdraw AEDs. The primary outcome measures are: 1) the outcome of the shared-decision making on AED withdrawal or continuation, and decision related arguments, and 2) seizure freedom at 12 months and 24 months of follow-up. We will also evaluate seizure type and frequency in case of seizure recurrence, as well as neurological symptoms, adverse effects related to AED treatment or withdrawal, other anti tumour treatments and tumour progression. DISCUSSION: This study addresses two issues that are currently unexplored. First, it will explore the willingness to withdraw AEDs in glioma patients, and second, it will assess the risk of seizure recurrence in case AEDs are withdrawn in this specific patient population. This study aims to contribute to a more tailored AED treatment, and prevent unnecessary and potentially harmful use of AEDs in glioma patients. PMID- 25124387 TI - Reconstitution of cytoskeletal protein assemblies for large-scale membrane transformation. AB - Membranes determine two-dimensional and three-dimensional biochemical reaction spaces in living systems. Defining size and shape of surfaces and volumes encompassed by membrane is of key importance for cellular metabolism and homeostasis, and the maintenance and controlled transformation of membrane shapes are coordinated by a large number of different protein assemblies. The orchestration of spatial elements over distances orders of magnitudes larger than protein molecules, as required for cell division, is a particularly challenging task, requiring large-scale ordered protein filaments and networks. The structure and function of these networks, particularly of cytoskeletal elements, have been characterized extensively in cells and reconstituted systems. However, their co reconstitution with membranes from the bottom-up under defined conditions, to elucidate their mode of action in detail, is still a relatively new field of research. In this short review, we discuss recent approaches and achievements with regard to the study of cytoskeletal protein assemblies on model membranes, with specific focus on contractile elements as those based on the bacterial division FtsZ protein and eukaryotic actomyosin structures. PMID- 25124388 TI - Combining quantitative trait loci analysis with physiological models to predict genotype-specific transpiration rates. AB - Transpiration is controlled by evaporative demand and stomatal conductance (gs ), and there can be substantial genetic variation in gs . A key parameter in empirical models of transpiration is minimum stomatal conductance (g0 ), a trait that can be measured and has a large effect on gs and transpiration. In Arabidopsis thaliana, g0 exhibits both environmental and genetic variation, and quantitative trait loci (QTL) have been mapped. We used this information to create a genetically parameterized empirical model to predict transpiration of genotypes. For the parental lines, this worked well. However, in a recombinant inbred population, the predictions proved less accurate. When based only upon their genotype at a single g0 QTL, genotypes were less distinct than our model predicted. Follow-up experiments indicated that both genotype by environment interaction and a polygenic inheritance complicate the application of genetic effects into physiological models. The use of ecophysiological or 'crop' models for predicting transpiration of novel genetic lines will benefit from incorporating further knowledge of the genetic control and degree of independence of core traits/parameters underlying gs variation. PMID- 25124389 TI - Clear cell urothelial carcinoma of the urinary bladder: a case report and review of the literature. AB - INTRODUCTION: The occurrence of clear cell tumors in the bladder is not uncommon. Clear cell dysplasia is well-described and characterized by focal replacement of transitional mucosa by cells with abundant clear cytoplasm, nuclear enlargement, and a granular chromatin pattern. Clear cells can also be seen in clear cell adenocarcinoma, which is rare, comprising 0.5% to 2.0% of the reported bladder carcinomas. Other clear cell tumors found in the bladder to be considered in the differential diagnosis are tumors of Mullerian origin and metastatic lesions, such as renal cell carcinoma, clear cell sarcoma, and malignant melanoma. Clear cell urothelial carcinoma is exceedingly rare, with only nine clinical cases described in the literature. CASE PRESENTATION: We report the case of a 75-year old Caucasian man who presented with intermittent hematuria, in whom a bladder tumor was identified. A final histopathology examination of a cystoprostatectomy specimen revealed a pT3b, G3 urothelial carcinoma of clear cell type (>90% clear cells) and a prostatic adenocarcinoma of Gleason grade 3+3 (score=6). The bladder tumor consisted of sheets of malignant cells with severe nuclear atypia and abundant clear cytoplasm; no glandular or tubular structures were identified. Tumor cells were periodic acid-Schiff positive and negative after diastase treatment; additional mucicarmine and oil red O stains were negative. Immunohistochemical stains showed the tumor cells positive for cytokeratin 7 (CK7), p63 (>80% nuclei), p53 (about 30% nuclei), vimentin, E-cadherin, cluster of differentiation (CD10), and Ki-67 (>70% nuclei). Stains for cell adhesion molecule 5.2 (CAM 5.2), CD117, cytokeratin 20 (CK20), human melanoma black 45 (HMB-45), paired box protein (PAX 8), placental alkaline phosphatase (PLAP), prostate specific antigen (PSA), renal cell carcinoma (RCC), cancer antigen 25 (CA25), leukocyte common antigen (LC), S-100 protein, and uroplakin III were all negative. CONCLUSIONS: The tumor marker profile was consistent with clear cell type carcinoma of urothelial origin. Within the differential diagnoses, we ruled out other possible tumor types such as urothelial carcinoma with focal clear cell differentiation, clear cell adenocarcinoma, Mullerian tumors, and metastatic disease. PMID- 25124390 TI - Finite element evaluation of three methods of stable fixation of condyle base fractures. AB - The surgical treatment of mandibular condyle fractures currently offers several possibilities for stable internal fixation. In this study, a finite element model evaluation was performed of three different methods for osteosynthesis of low subcondylar fractures: (1) two four-hole straight plates, (2) one seven-hole lambda plate, and (3) one four-hole trapezoidal plate. The finite element model evaluation considered a load applied to the first molar on the contralateral side to the fracture. Results showed that, although the three methods are capable of withstanding functional loading, the lambda plate displayed a more homogeneous stress distribution for both osteosynthesis material and bone and may be a better method when single-plate fixation is the option. PMID- 25124391 TI - Palatal osteotomy with vestibuloplasty for the treatment of severe maxillary atrophy: a new twist on an old technique. AB - Nowadays, upper denture instability secondary to severe maxillary atrophy is treated, in most cases, with dental implants. However, a significant number of patients cannot afford this procedure. Palatal bone deepening through a U-shaped osteotomy has been described previously. The procedure increases retention by improving the suction effect of the palate and prevents anteroposterior and lateral movement of the denture. By combining this procedure with a secondary epithelialization vestibuloplasty, the labial aspect of the ridge is also extended and it does not require a skin graft. This article describes a modification of the palatal vault osteotomy through the presentation of a case. PMID- 25124392 TI - UDP-galactose 4'-epimerase from the liver fluke, Fasciola hepatica: biochemical characterization of the enzyme and identification of inhibitors. AB - Leloir pathway enzyme uridine diphosphate (UDP)-galactose 4'-epimerase from the common liver fluke Fasciola hepatica (FhGALE) was identified and characterized. The enzyme can be expressed in, and purified from, Escherichia coli. The recombinant enzyme is active: the K(m) (470 MUM) is higher than the corresponding human enzyme (HsGALE), whereas the k(cat) (2.3 s(-1)) is substantially lower. FhGALE binds NAD(+) and has shown to be dimeric by analytical gel filtration. Like the human and yeast GALEs, FhGALE is stabilized by the substrate UDP galactose. Molecular modelling predicted that FhGALE adopts a similar overall fold to HsGALE and that tyrosine 155 is likely to be the catalytically critical residue in the active site. In silico screening of the National Cancer Institute Developmental Therapeutics Program library identified 40 potential inhibitors of FhGALE which were tested in vitro. Of these, 6 showed concentration-dependent inhibition of FhGALE, some with nanomolar IC50 values. Two inhibitors (5 fluoroorotate and N-[(benzyloxy)carbonyl]leucyltryptophan) demonstrated selectivity for FhGALE over HsGALE. These compounds also thermally destabilized FhGALE in a concentration-dependent manner. Interestingly, the selectivity of 5 fluoroorotate was not shown by orotic acid, which differs in structure by 1 fluorine atom. These results demonstrate that, despite the structural and biochemical similarities of FhGALE and HsGALE, it is possible to discover compounds which preferentially inhibit FhGALE. PMID- 25124394 TI - Multi-stakeholder collaboration in the redesign of family-centered rounds process. AB - A human factors approach to healthcare system redesign emphasizes the involvement of multiple healthcare stakeholders (e.g., patients and families, healthcare providers) in the redesign process. This study explores the experience of multiple stakeholders with collaboration in a healthcare system redesign project. Interviews were conducted with ten stakeholder representatives who participated in the redesign of the family-centered rounds process in a pediatric hospital. Qualitative interview data were analyzed using a phenomenological approach. A model of collaborative healthcare system redesign was developed, which defined four phases (i.e., setup of the redesign team, preparation for meetings, collaboration in meetings, follow-up after meetings) and two outcomes (i.e., team outcomes, redesign outcomes) of the collaborative process. Challenges to multi stakeholder collaboration in healthcare system redesign, such as need to represent all relevant stakeholders, scheduling of meetings and managing different perspectives, were identified. PMID- 25124395 TI - Supraglottitis due to group B streptococcus in an adult with IgG4 and C2 deficiency: a case report and review of the literature. AB - Acute supraglottitis is a medical emergency as it can rapidly lead to airway compromise. With routine pediatric immunization for Hemophilus influenzae serotype b, supraglottitis is now more prevalent in adults, with a shift in the causative organisms and a change in the natural history of this disease. Here, we present a case of supraglottitis due to group B streptococcus that occurred in an adult with previously undetected immunoglobulin 4 (IgG4) and complement protein C2 deficiency. PMID- 25124396 TI - Effects of data sampling on graphical depictions of learning. AB - Continuous and discontinuous data-collection methods were compared in the context of discrete-trial programming. Archival data sets were analyzed using trial sampling (1st 5 trials, 1st 3 trials, and 1st trial only) and session sampling (every other session, every 3rd session, and every 5th session). Results showed that trial sampling systematically underestimated the number of sessions and days to mastery and overestimated the number of sessions and days to the 1st independent response. Session sampling systematically overestimated both sessions and days to mastery and sessions and days to the 1st independent response. A time savings analysis was included to evaluate empirically how much time would be saved by using each sampling method. Results suggested that data sampling would produce relatively minimal time savings. PMID- 25124393 TI - Influence of noninjecting and injecting drug use on mortality, retention in the cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort Study. AB - OBJECTIVES: We studied the influence of noninjecting and injecting drug use on mortality, dropout rate, and the course of antiretroviral therapy (ART), in the Swiss HIV Cohort Study (SHCS). METHODS: Cohort participants, registered prior to April 2007 and with at least one drug use questionnaire completed until May 2013, were categorized according to their self-reported drug use behaviour. The probabilities of death and dropout were separately analysed using multivariable competing risks proportional hazards regression models with mutual correction for the other endpoint. Furthermore, we describe the influence of drug use on the course of ART. RESULTS: A total of 6529 participants (including 31% women) were followed during 31 215 person-years; 5.1% participants died; 10.5% were lost to follow-up. Among persons with homosexual or heterosexual HIV transmission, noninjecting drug use was associated with higher all-cause mortality [subhazard rate (SHR) 1.73; 95% confidence interval (CI) 1.07-2.83], compared with no drug use. Also, mortality was increased among former injecting drug users (IDUs) who reported noninjecting drug use (SHR 2.34; 95% CI 1.49-3.69). Noninjecting drug use was associated with higher dropout rates. The mean proportion of time with suppressed viral replication was 82.2% in all participants, irrespective of ART status, and 91.2% in those on ART. Drug use lowered adherence, and increased rates of ART change and ART interruptions. Virological failure on ART was more frequent in participants who reported concomitant drug injections while on opiate substitution, and in current IDUs, but not among noninjecting drug users. CONCLUSIONS: Noninjecting drug use and injecting drug use are modifiable risks for death, and they lower retention in a cohort and complicate ART. PMID- 25124398 TI - Bipolar stacked quasi-all-solid-state lithium secondary batteries with output cell potentials of over 6 V. AB - Designing a lithium ion battery (LIB) with a three-dimensional device structure is crucial for increasing the practical energy storage density by avoiding unnecessary supporting parts of the cell modules. Here, we describe the superior secondary battery performance of the bulk all-solid-state LIB cell and a multilayered stacked bipolar cell with doubled cell potential of 6.5 V, for the first time. The bipolar-type solid LIB cell runs its charge/discharge cycle over 200 times in a range of 0.1-1.0 C with negligible capacity decrease despite their doubled output cell potentials. This extremely high performance of the bipolar cell is a result of the superior battery performance of the single cell; the bulk all-solid-state cell has a charge/discharge cycle capability of over 1500 although metallic lithium and LiFePO4 are employed as anodes and cathodes, respectively. The use of a quasi-solid electrolyte consisting of ionic liquid and Al2O3 nanoparticles is considered to be responsible for the high ionic conductivity and electrochemical stability at the interface between the electrodes and the electrolyte. This paper presents the effective applications of SiO2, Al2O3, and CeO2 nanoparticles and various Li(+) conducting ionic liquids for the quasi-solid electrolytes and reports the best ever known cycle performances. Moreover, the results of this study show that the bipolar stacked three-dimensional device structure would be a smart choice for future LIBs with higher cell energy density and output potential. In addition, our report presents the advantages of adopting a three-dimensional cell design based on the solid state electrolytes, which is of particular interest in energy-device engineering for mobile applications. PMID- 25124399 TI - Misfolding of luciferase at the single-molecule level. AB - The folding of complex proteins can be dramatically affected by misfolding transitions. Directly observing misfolding and distinguishing it from aggregation is challenging. Experiments with optical tweezers revealed transitions between the folded states of a single protein in the absence of mechanical tension. Nonfolded chains of the multidomain protein luciferase folded within seconds to different partially folded states, one of which was stable over several minutes and was more resistant to forced unfolding than other partially folded states. Luciferase monomers can thus adopt a stable misfolded state and can do so without interacting with aggregation partners. This result supports the notion that luciferase misfolding is the cause of the low refolding yields and aggregation observed with this protein. This approach could be used to study misfolding transitions in other large proteins, as well as the factors that affect misfolding. PMID- 25124397 TI - Use of a murine embryonic stem cell line that is sensitive to high glucose environment to model neural tube development in diabetic pregnancy. AB - BACKGROUND: Neural tube defects (NTDs) are significantly increased by maternal diabetes. Embryonic stem cells (ESC) that can differentiate into neuroepithelium and can sense supraphysiological glucose concentrations would be very valuable to simulate the effects of maternal diabetes on molecular and cellular processes during neural tube formation. METHODS: LG-ESC, a recently established ESC line that expresses the glucose transporter, Scl2a2, and is sensitive to elevated glucose concentrations, were grown for up to 8 days in a three-dimensional culture to form neural cysts. We tested whether high glucose media inhibits expression of Pax3, a gene that is required for neural tube closure and whose expression is inhibited in embryos of diabetic mice, and inhibits formation of neural cysts. RESULTS: Pax3 expression was detected after 4 days of culture and increased with time. Pax3 expression was inhibited by high glucose media, but not if cells had been cultured in low glucose media for the first 4 days of culture. Pax7, which is also expressed in dorsal neural tube, was not detected. Pax6, which is expressed in the ventral neural tube, was detected only after 8 days of culture, but was not inhibited by high glucose. High glucose media did not inhibit formation of neural cysts. CONCLUSION: LG-ESC can be used as a model of embryonic exposure to a diabetic environment during neural tube development. While high glucose exposure inhibits expression of a gene required for neural tube closure, it may not inhibit all of the processes involved in formation of a neural tube-like structure. PMID- 25124400 TI - Predicting the conservation status of data-deficient species. AB - There is little appreciation of the level of extinction risk faced by one-sixth of the over 65,000 species assessed by the International Union for Conservation of Nature. Determining the status of these data-deficient (DD) species is essential to developing an accurate picture of global biodiversity and identifying potentially threatened DD species. To address this knowledge gap, we used predictive models incorporating species' life history, geography, and threat information to predict the conservation status of DD terrestrial mammals. We constructed the models with 7 machine learning (ML) tools trained on species of known status. The resultant models showed very high species classification accuracy (up to 92%) and ability to correctly identify centers of threatened species richness. Applying the best model to DD species, we predicted 313 of 493 DD species (64%) to be at risk of extinction, which increases the estimated proportion of threatened terrestrial mammals from 22% to 27%. Regions predicted to contain large numbers of threatened DD species are already conservation priorities, but species in these areas show considerably higher levels of risk than previously recognized. We conclude that unless directly targeted for monitoring, species classified as DD are likely to go extinct without notice. Taking into account information on DD species may therefore help alleviate data gaps in biodiversity indicators and conserve poorly known biodiversity. PMID- 25124402 TI - Science for lasting peace. PMID- 25124401 TI - The interrelationship between anti-Mullerian hormone, ovarian follicular populations and age in mares. AB - REASONS FOR PERFORMING STUDY: Anti-Mullerian hormone (AMH) is a granulosa-cell derived glycoprotein, which plays an important inhibitory role during folliculogenesis. Concentrations of AMH are highly correlated with antral follicle counts (AFCs) in other species, which in turn are related to follicular reserve. Relatively little is known about AMH and AFC in the mare. OBJECTIVES: To determine plasma AMH concentrations and AFCs in mares of different ages, to measure the repeatability of AMH concentrations and AFCs within and across oestrous cycles and to assess the relationship between plasma AMH concentrations and AFCs with regard to mare age and follicle size. STUDY DESIGN: An observational study examining the relationship between AMH, AFC and age in 45 mares. METHODS: Young (3-8 years), middle-aged (9-18 years) and old mares (19-27 years) were examined by transrectal ultrasonography over 2 or 3 oestrous cycles. Plasma AMH concentrations and AFCs were determined, and antral follicles were classified by size into different groups. RESULTS: Plasma AMH concentrations varied widely between mares within similar age groups. Antral follicle counts were significantly lower in old mares than in young and middle-aged mares, and AMH concentrations were significantly lower in old than in middle-aged mares. A positive relationship was detected between AFC and AMH, and this relationship varied by mare age with a strong correlation in older mares (rho = 0.86; P<0.0001), a moderate correlation in middle-aged mares (rho = 0.60; P = 0.01) and no correlation in young mares (rho = 0.40, P<0.4). The AMH concentrations were significantly related to the number of antral follicles between 6 and 20 mm in diameter, and the repeatability of AFCs and AMH concentrations was high within and between oestrous cycles. CONCLUSIONS: Our findings indicate that the relationship between AMH and AFC varies across age groups, and concentrations of AMH might be a better reflection of reproductive age than calendar age. PMID- 25124405 TI - Nuclear weapons. Firing of Los Alamos researcher draws criticism. PMID- 25124404 TI - Infectious diseases. Debate erupts on 'repurposed' drugs for Ebola. PMID- 25124406 TI - Earth science. A boom in boomless seismology. PMID- 25124407 TI - The rising toll. PMID- 25124408 TI - Civilian casualties in Afghanistan. PMID- 25124409 TI - Mother of all lodes. PMID- 25124410 TI - Information technology. Technology's limited role in resolving debates over digital surveillance. PMID- 25124411 TI - Medicine. Letting go of mucus. PMID- 25124412 TI - Chemistry. Self-assembled RNA nanostructures. PMID- 25124414 TI - Water treatment. Replace contamination, not the pipes. PMID- 25124413 TI - Epigenetics. You are what you eat, but what about your DNA? PMID- 25124415 TI - Biochemistry. One step closer to O2. PMID- 25124416 TI - HIV cover ill-advised. PMID- 25124417 TI - HIV cover ill-advised--response. PMID- 25124418 TI - Climate change: time to navigate. PMID- 25124419 TI - Fossil fuels' future. PMID- 25124420 TI - Sharing ideas too soon. PMID- 25124421 TI - Outside the Tower. Kids' questions transcend conflict. PMID- 25124422 TI - Parenting. A legacy that transcends genes. Introduction. PMID- 25124423 TI - Unsettled questions trail IVF's success. PMID- 25124424 TI - Nature's first functional food. PMID- 25124425 TI - The taste of things to come. PMID- 25124426 TI - An experiment in zero parenting. PMID- 25124427 TI - Maternal mental illness. PMID- 25124428 TI - Parenting from before conception. AB - At fertilization, the gametes endow the embryo with a genomic blueprint, the integrity of which is affected by the age and environmental exposures of both parents. Recent studies reveal that parental history and experiences also exert effects through epigenomic information not contained in the DNA sequence, including variations in sperm and oocyte cytosine methylation and chromatin patterning, noncoding RNAs, and mitochondria. Transgenerational epigenetic effects interact with conditions at conception to program the developmental trajectory of the embryo and fetus, ultimately affecting the lifetime health of the child. These insights compel us to revise generally held notions to accommodate the prospect that biological parenting commences well before birth, even prior to conception. PMID- 25124429 TI - Preterm labor: one syndrome, many causes. AB - Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment. PMID- 25124432 TI - The evolution of flexible parenting. AB - Parenting behaviors, such as the provisioning of food by parents to offspring, are known to be highly responsive to changes in environment. However, we currently know little about how such flexibility affects the ways in which parenting is adapted and evolves in response to environmental variation. This is because few studies quantify how individuals vary in their response to changing environments, especially social environments created by other individuals with which parents interact. Social environmental factors differ from nonsocial factors, such as food availability, because parents and offspring both contribute and respond to the social environment they experience. This interdependence leads to the coevolution of flexible behaviors involved in parenting, which could, paradoxically, constrain the ability of individuals to rapidly adapt to changes in their nonsocial environment. PMID- 25124430 TI - Neural control of maternal and paternal behaviors. AB - Parental care, including feeding and protection of young, is essential for the survival as well as mental and physical well-being of the offspring. A large variety of parental behaviors has been described across species and sexes, raising fascinating questions about how animals identify the young and how brain circuits drive and modulate parental displays in males and females. Recent studies have begun to uncover a striking antagonistic interplay between brain systems underlying parental care and infant-directed aggression in both males and females, as well as a large range of intrinsic and environmentally driven neural modulation and plasticity. Improved understanding of the neural control of parental interactions in animals should provide novel insights into the complex issue of human parental care in both health and disease. PMID- 25124431 TI - The biology of mammalian parenting and its effect on offspring social development. AB - Parents know the transformative nature of having and caring for a child. Among many mammals, giving birth leads from an aversion to infant stimuli to irresistible attraction. Here, we review the biological mechanisms governing this shift in parental motivation in mammals. Estrogen and progesterone prepare the uterus for embryo implantation and placental development. Prolactin stimulates milk production, whereas oxytocin initiates labor and triggers milk ejection during nursing. These same molecules, interacting with dopamine, also activate specific neural pathways to motivate parents to nurture, bond with, and protect their offspring. Parenting in turn shapes the neural development of the infant social brain. Recent work suggests that many of the principles governing parental behavior and its effect on infant development are conserved from rodent to humans. PMID- 25124434 TI - Interstellar medium. Pseudo-three-dimensional maps of the diffuse interstellar band at 862 nm. AB - The diffuse interstellar bands (DIBs) are absorption lines observed in visual and near-infrared spectra of stars. Understanding their origin in the interstellar medium is one of the oldest problems in astronomical spectroscopy, as DIBs have been known since 1922. In a completely new approach to understanding DIBs, we combined information from nearly 500,000 stellar spectra obtained by the massive spectroscopic survey RAVE (Radial Velocity Experiment) to produce the first pseudo-three-dimensional map of the strength of the DIB at 8620 angstroms covering the nearest 3 kiloparsecs from the Sun, and show that it follows our independently constructed spatial distribution of extinction by interstellar dust along the Galactic plane. Despite having a similar distribution in the Galactic plane, the DIB 8620 carrier has a significantly larger vertical scale height than the dust. Even if one DIB may not represent the general DIB population, our observations outline the future direction of DIB research. PMID- 25124435 TI - Robotics. Programmable self-assembly in a thousand-robot swarm. AB - Self-assembly enables nature to build complex forms, from multicellular organisms to complex animal structures such as flocks of birds, through the interaction of vast numbers of limited and unreliable individuals. Creating this ability in engineered systems poses challenges in the design of both algorithms and physical systems that can operate at such scales. We report a system that demonstrates programmable self-assembly of complex two-dimensional shapes with a thousand robot swarm. This was enabled by creating autonomous robots designed to operate in large groups and to cooperate through local interactions and by developing a collective algorithm for shape formation that is highly robust to the variability and error characteristic of large-scale decentralized systems. This work advances the aim of creating artificial swarms with the capabilities of natural ones. PMID- 25124433 TI - Interstellar dust. Evidence for interstellar origin of seven dust particles collected by the Stardust spacecraft. AB - Seven particles captured by the Stardust Interstellar Dust Collector and returned to Earth for laboratory analysis have features consistent with an origin in the contemporary interstellar dust stream. More than 50 spacecraft debris particles were also identified. The interstellar dust candidates are readily distinguished from debris impacts on the basis of elemental composition and/or impact trajectory. The seven candidate interstellar particles are diverse in elemental composition, crystal structure, and size. The presence of crystalline grains and multiple iron-bearing phases, including sulfide, in some particles indicates that individual interstellar particles diverge from any one representative model of interstellar dust inferred from astronomical observations and theory. PMID- 25124436 TI - RNA nanostructures. A single-stranded architecture for cotranscriptional folding of RNA nanostructures. AB - Artificial DNA and RNA structures have been used as scaffolds for a variety of nanoscale devices. In comparison to DNA structures, RNA structures have been limited in size, but they also have advantages: RNA can fold during transcription and thus can be genetically encoded and expressed in cells. We introduce an architecture for designing artificial RNA structures that fold from a single strand, in which arrays of antiparallel RNA helices are precisely organized by RNA tertiary motifs and a new type of crossover pattern. We constructed RNA tiles that assemble into hexagonal lattices and demonstrated that lattices can be made by annealing and/or cotranscriptional folding. Tiles can be scaled up to 660 nucleotides in length, reaching a size comparable to that of large natural ribozymes. PMID- 25124437 TI - Photosynthesis. Electronic structure of the oxygen-evolving complex in photosystem II prior to O-O bond formation. AB - The photosynthetic protein complex photosystem II oxidizes water to molecular oxygen at an embedded tetramanganese-calcium cluster. Resolving the geometric and electronic structure of this cluster in its highest metastable catalytic state (designated S3) is a prerequisite for understanding the mechanism of O-O bond formation. Here, multifrequency, multidimensional magnetic resonance spectroscopy reveals that all four manganese ions of the catalyst are structurally and electronically similar immediately before the final oxygen evolution step; they all exhibit a 4+ formal oxidation state and octahedral local geometry. Only one structural model derived from quantum chemical modeling is consistent with all magnetic resonance data; its formation requires the binding of an additional water molecule. O-O bond formation would then proceed by the coupling of two proximal manganese-bound oxygens in the transition state of the cofactor. PMID- 25124438 TI - Plant science. Genomic-scale exchange of mRNA between a parasitic plant and its hosts. AB - Movement of RNAs between cells of a single plant is well documented, but cross species RNA transfer is largely unexplored. Cuscuta pentagona (dodder) is a parasitic plant that forms symplastic connections with its hosts and takes up host messenger RNAs (mRNAs). We sequenced transcriptomes of Cuscuta growing on Arabidopsis and tomato hosts to characterize mRNA transfer between species and found that mRNAs move in high numbers and in a bidirectional manner. The mobile transcripts represented thousands of different genes, and nearly half the expressed transcriptome of Arabidopsis was identified in Cuscuta. These findings demonstrate that parasitic plants can exchange large proportions of their transcriptomes with hosts, providing potential mechanisms for RNA-based interactions between species and horizontal gene transfer. PMID- 25124439 TI - Water engineering. Reducing sewer corrosion through integrated urban water management. AB - Sewer systems are among the most critical infrastructure assets for modern urban societies and provide essential human health protection. Sulfide-induced concrete sewer corrosion costs billions of dollars annually and has been identified as a main cause of global sewer deterioration. We performed a 2-year sampling campaign in South East Queensland (Australia), an extensive industry survey across Australia, and a comprehensive model-based scenario analysis of the various sources of sulfide. Aluminum sulfate addition during drinking water production contributes substantially to the sulfate load in sewage and indirectly serves as the primary source of sulfide. This unintended consequence of urban water management structures could be avoided by switching to sulfate-free coagulants, with no or only marginal additional expenses compared with the large potential savings in sewer corrosion costs. PMID- 25124440 TI - Place cells. Large environments reveal the statistical structure governing hippocampal representations. AB - The rules governing the formation of spatial maps in the hippocampus have not been determined. We investigated the large-scale structure of place field activity by recording hippocampal neurons in rats exploring a previously unencountered 48-meter-long track. Single-cell and population activities were well described by a two-parameter stochastic model. Individual neurons had their own characteristic propensity for forming fields randomly along the track, with some cells expressing many fields and many exhibiting few or none. Because of the particular distribution of propensities across cells, the number of neurons with fields scaled logarithmically with track length over a wide, ethological range. These features constrain hippocampal memory mechanisms, may allow efficient encoding of environments and experiences of vastly different extents and durations, and could reflect general principles of population coding. PMID- 25124444 TI - Outside my comfort zone. PMID- 25124442 TI - Transdifferentiation. Sequential histone-modifying activities determine the robustness of transdifferentiation. AB - Natural interconversions between distinct somatic cell types have been reported in species as diverse as jellyfish and mice. The efficiency and reproducibility of some reprogramming events represent unexploited avenues in which to probe mechanisms that ensure robust cell conversion. We report that a conserved H3K27me3/me2 demethylase, JMJD-3.1, and the H3K4 methyltransferase Set1 complex cooperate to ensure invariant transdifferentiation (Td) of postmitotic Caenorhabditis elegans hindgut cells into motor neurons. At single-cell resolution, robust conversion requires stepwise histone-modifying activities, functionally partitioned into discrete phases of Td through nuclear degradation of JMJD-3.1 and phase-specific interactions with transcription factors that have conserved roles in cell plasticity and terminal fate selection. Our results draw parallels between epigenetic mechanisms underlying robust Td in nature and efficient cell reprogramming in vitro. PMID- 25124443 TI - Synthetic biology. Programmable on-chip DNA compartments as artificial cells. AB - The assembly of artificial cells capable of executing synthetic DNA programs has been an important goal for basic research and biotechnology. We assembled two dimensional DNA compartments fabricated in silicon as artificial cells capable of metabolism, programmable protein synthesis, and communication. Metabolism is maintained by continuous diffusion of nutrients and products through a thin capillary, connecting protein synthesis in the DNA compartment with the environment. We programmed protein expression cycles, autoregulated protein levels, and a signaling expression gradient, equivalent to a morphogen, in an array of interconnected compartments at the scale of an embryo. Gene expression in the DNA compartment reveals a rich, dynamic system that is controlled by geometry, offering a means for studying biological networks outside a living cell. PMID- 25124441 TI - Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. AB - Lung disease in people with cystic fibrosis (CF) is initiated by defective host defense that predisposes airways to bacterial infection. Advanced CF is characterized by a deficit in mucociliary transport (MCT), a process that traps and propels bacteria out of the lungs, but whether this deficit occurs first or is secondary to airway remodeling has been unclear. To assess MCT, we tracked movement of radiodense microdisks in airways of newborn piglets with CF. Cholinergic stimulation, which elicits mucus secretion, substantially reduced microdisk movement. Impaired MCT was not due to periciliary liquid depletion; rather, CF submucosal glands secreted mucus strands that remained tethered to gland ducts. Inhibiting anion secretion in non-CF airways replicated CF abnormalities. Thus, impaired MCT is a primary defect in CF, suggesting that submucosal glands and tethered mucus may be targets for early CF treatment. PMID- 25124446 TI - Serum protein profiles, circulating immune complexes and proteinuria in dogs naturally infected with Anaplasma phagocytophilum. AB - Alterations in serum protein profile, presence of circulating immune complexes (CIC) and proteinuria were investigated in a large group of dogs naturally infected with the Anaplasma phagocytophilum bacterium. Our aim was to evaluate the presence of hypergammaglobulinaemia, CIC and proteinuria as a possible result of an immune-mediated disease following infection by or exposure to A. phagocytophilum. Dogs were divided into three groups - IFA positive (188 dogs with confirmed exposure to A. phagocytophilum), PCR positive (31 dogs with confirmed infection), and control (IFA and PCR negative) (19 dogs). Serum and urine protein patterns were determined by electrophoresis and CIC concentrations by absorbance nephelometry. No significant differences in hypergammaglobulinaemia were observed between the different groups, as shown by the presence of acute phase proteins alpha2 and beta1-2 globulins. CIC concentrations in the IFA and PCR positive groups were, on average, higher than in controls by 151.3MUg/ml, though the differences were not significant. The proportion of dogs with proteinuria did not differ significantly between groups. Our results confirm the assumption that anaplasmosis in dogs is most probably a disease with an acute course, with a good prognosis under the right treatment. PMID- 25124447 TI - Molecular detection and genotyping of Aphanomyces astaci directly from preserved crayfish samples uncovers the Norwegian crayfish plague disease history. AB - Aphanomyces astaci causes crayfish plague in European freshwater crayfish, but most historical epizootics lack agent isolation and identification. Although declared as crayfish plague outbreaks by the Norwegian Competent Authorities, only presumptive diagnoses without agent isolation exist from Norwegian epizootics until 2005. Molecular methods now allow both A. astaci detection and genotype determination from preserved samples. We therefore aimed to (1) investigate molecularly if A. astaci was involved in a selection of mass mortality events in Norwegian noble crayfish populations from 1971 to 2004, and (2) determine the eventually involved A. astaci genotype groups both from these historical and also more recent mass-mortality events. DNA was extracted directly from presumptively infected crayfish tissues, and screened by A. astaci specific qPCR. A representative selection of positive samples was confirmed by ITS sequencing. Finally, genotype determination was performed with microsatellite markers that distinguish all known A. astaci genotype groups. The molecular examination detected A. astaci in crayfish materials from all examined mass mortality events. The first event in 1971-1974 was caused by the A. astaci genotype group A, presumably the first genotype group that entered Europe more than 150 years ago. All later outbreaks were caused by the A. astaci genotype group B which was introduced to Europe by importation of signal crayfish in the 1960s. The results suggest that molecular methods can verify the involvement of A. astaci in the vast majority of observed crayfish mass mortalities in Europe whenever preserved materials exist. Moreover, microsatellite genotyping can reveal at least parts of the underlying epidemiology. PMID- 25124448 TI - Development of an APP Helpful to Manage Patients with Low Back Pain. PMID- 25124450 TI - Evaluation of sphingomyelin, cholester, and phosphatidylcholine-based immobilized artificial membrane liquid chromatography to predict drug penetration across the blood-brain barrier. AB - Over the past decades, several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier. So far, in high-performance liquid chromatography, most attention has been paid to micellar liquid chromatography and immobilized artificial membrane (IAM) LC. IAMLC has been described as a viable approach, since the stationary phase emulates the lipid environment of a cell membrane. However, research in IAMLC has almost exclusively been limited to phosphatidylcholine (PC)-based stationary phases, even though PC is only one of the lipids present in cell membranes. In this article, sphingomyelin and cholester stationary phases have been tested for the first time towards their ability to predict drug penetration across the blood brain barrier. Upon comparison with the PC stationary phase, the sphingomyelin- and cholester-based columns depict similar predictive performance. Combining data from the different stationary phases did not lead to improvements of the models. PMID- 25124453 TI - Nephrotic syndrome in hand, foot and mouth disease caused by coxsackievirus A16: a case report. AB - Some viruses, including certain members of the enterovirus genus, have been reported to cause nephrotic syndrome. However, no case of coxsackievirus A16 (CVA16)-related nephrotic syndrome has been reported so far. We describe a case of CVA16-related hand, foot and mouth disease presenting with nephrotic syndrome in a 3-year-old boy. This is the first report of CVA16-related nephrotic syndrome. PMID- 25124454 TI - On confirmation bias in imaging research. PMID- 25124452 TI - The absence of exanthema is related with death and illness severity in acute enterovirus infection. AB - OBJECTIVE: To clarify whether exanthema is related to illness severity in acute enterovirus infection in children. METHODS: The data of pediatric inpatients at Zhujiang Hospital during 2009-2012 with an acute enterovirus infection were reviewed retrospectively. Enterovirus infection was determined by real-time reverse transcription PCR. Clinical data were summarized and compared between cases with and without exanthema. RESULTS: A total of 780 pediatric inpatients with an acute enterovirus infection were included in this study, of whom 83 (10.6%) presented no exanthema. The percentage of deaths in the group of patients without exanthema was significantly higher than that in the group with exanthema (7.2% vs. 1.1%; p = 0.002). Central nervous system involvement (41.0% vs. 30.0%; p = 0.041), severe central nervous system (CNS) involvement (21.7% vs. 11.0%; p = 0.005), severe CNS involvement with cardiopulmonary failure (9.6% vs. 2.3%; p = 0.002), an altered level of consciousness (15.7% vs. 7.6%; p = 0.013), and convulsions (14.4% vs. 6.3%; p = 0.007) occurred significantly more frequently in the group without exanthema. CONCLUSIONS: A considerable proportion of children with an acute enterovirus infection in Guangdong Province, China during 2009-2012 presented no exanthema, and the absence of exanthema was found to be related to death and illness severity for these acute enterovirus infections. Clinicians in China should consider enterovirus as the possible pathogen when treating children with an acute pathogen infection without exanthema. PMID- 25124451 TI - Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice. AB - Hearing relies on the mechanosensory inner and outer hair cells (OHCs) of the organ of Corti, which convert mechanical deflections of their actin-rich stereociliary bundles into electrochemical signals. Several actin-associated proteins are essential for stereocilia formation and maintenance, and their absence leads to deafness. One of the most abundant actin-bundling proteins of stereocilia is plastin 1, but its function has never been directly assessed. Here, we found that plastin 1 knock-out (Pls1 KO) mice have a moderate and progressive form of hearing loss across all frequencies. Auditory hair cells developed normally in Pls1 KO, but in young adult animals, the stereocilia of inner hair cells were reduced in width and length. The stereocilia of OHCs were comparatively less affected; however, they also showed signs of degeneration in ageing mice. The hair bundle stiffness and the acquisition of the electrophysiological properties of hair cells were unaffected by the absence of plastin 1, except for a significant change in the adaptation properties, but not the size of the mechanoelectrical transducer currents. These results show that in contrast to other actin-bundling proteins such as espin, harmonin or Eps8, plastin 1 is dispensable for the initial formation of stereocilia. However, the progressive hearing loss and morphological defects of hair cells in adult Pls1 KO mice point at a specific role for plastin 1 in the preservation of adult stereocilia and optimal hearing. Hence, mutations in the human PLS1 gene may be associated with relatively mild and progressive forms of hearing loss. PMID- 25124455 TI - Refinement of the critical region in a new 7p22.1 microduplication syndrome including craniofacial dysmorphism and speech delay. PMID- 25124457 TI - Intimacy motivations and pre-exposure prophylaxis (PrEP) adoption intentions among HIV-negative men who have sex with men (MSM) in romantic relationships. AB - BACKGROUND: In the USA, men who have sex with men (MSM) in primary partnerships are at elevated risk for human immunodeficiency virus (HIV) infection. Pre exposure prophylaxis (PrEP), a new biomedical prevention strategy, has potential to reduce HIV transmission. This study examined predictors of PrEP adoption intentions among HIV-negative MSM in primary partnerships. METHODS: The sample included HIV-negative MSM (n = 164) who participated in an ongoing cross sectional study with an in-person interview examining PrEP adoption intentions. RESULTS: Higher HIV risk perception, intimacy motivations for condomless sex, recent condomless anal sex with outside partners, education, and age were each independently associated with PrEP adoption intentions. In a multivariate model, only age, education, and intimacy motivations for condomless sex were significantly associated with PrEP adoption intentions. CONCLUSIONS: Intimacy motivations may play a central role in PrEP adoption for MSM couples. Incorporating relationship dynamics into biomedical strategies is a promising avenue for research and intervention. PMID- 25124456 TI - Randomized controlled trial of Qigong/Tai Chi Easy on cancer-related fatigue in breast cancer survivors. AB - BACKGROUND: Many breast cancer survivors experience fatigue, mood, and sleep disturbances. PURPOSE: This study aims to compare a meditative movement practice, Qigong/Tai Chi Easy (QG/TCE) with sham Qigong (SQG), testing effects of meditation/breath aspects of QG/TCE on breast cancer survivors' persistent fatigue and other symptoms. METHODS: This double-blind, randomized controlled trial tested 12 weeks of QG/TCE versus SQG on fatigue, depression, and sleep among 87 postmenopausal, fatigued breast cancer survivors, stages 0-III, age 40 75. RESULTS: Fatigue decreased significantly in the QG/TCE group compared to control at post-intervention (p = 0.005) and 3 months follow-up (p = 0.024), but not depression and sleep quality. Improvement occurred over time for both interventions in depression and sleep quality (all p < 0.05). CONCLUSIONS: QG/TCE showed significant improvement over time compared to SQG for fatigue, but not depression or sleep. Both QG/TCE and SQG showed improvement for two prevalent symptoms among breast cancer survivors, depression and sleep dysfunction. PMID- 25124459 TI - The conservative management of renal trauma: a literature review and practical clinical guideline from Australia and New Zealand. AB - OBJECTIVE: To review the literature and make practical recommendations regarding the conservative management of renal trauma. PATIENTS AND METHODS: Relevant articles and guidelines published between 1980 and 2014 were reviewed. Graded recommendations were constructed by a multi-disciplinary panel consisting of urologists, radiologists, and infectious disease physicians. These recommendations underwent formal review and debate at the Western Australian USANZ 2013 state conference, and were presented at the USANZ 2014 annual scientific meeting. RESULTS: The literature on the conservative management of renal trauma is reviewed within the framework of the American Association for the Surgery of Trauma (AAST) kidney injury severity scale. Graded recommendations are made regarding several key topics including: imaging, inpatient management, antibiotics, return to activity, and follow-up. Grade IV injuries and intraoperative consults are examined separately in view of the difficulties these groups cause in making appropriate treatment decisions. CONCLUSION: A practical clinical guideline is provided regarding the conservative management of renal trauma. PMID- 25124458 TI - Microtubules provide directional information for core PCP function. AB - Planar cell polarity (PCP) signaling controls the polarization of cells within the plane of an epithelium. Two molecular modules composed of Fat(Ft)/Dachsous(Ds)/Four-jointed(Fj) and a 'PCP-core' including Frizzled(Fz) and Dishevelled(Dsh) contribute to polarization of individual cells. How polarity is globally coordinated with tissue axes is unresolved. Consistent with previous results, we find that the Ft/Ds/Fj-module has an effect on a MT-cytoskeleton. Here, we provide evidence for the model that the Ft/Ds/Fj-module provides directional information to the core-module through this MT organizing function. We show Ft/Ds/Fj-dependent initial polarization of the apical MT-cytoskeleton prior to global alignment of the core-module, reveal that the anchoring of apical non-centrosomal MTs at apical junctions is polarized, observe that directional trafficking of vesicles containing Dsh depends on Ft, and demonstrate the feasibility of this model by mathematical simulation. Together, these results support the hypothesis that Ft/Ds/Fj provides a signal to orient core PCP function via MT polarization. PMID- 25124463 TI - Assembling ellipsoidal particles at fluid interfaces using switchable dipolar capillary interactions. AB - How to dynamically tune an assembly of anisotropic colloidal particles adsorbed at fluid-fluid interfaces using dipolar capillary interactions is demonstrated. A previously discovered first-order phase transition is exploited and it is shown how to spontaneously turn off these dipolar capillary interactions by exceeding a critical field strength, providing unprecedented control of the bottom-up fabrication of soft materials. PMID- 25124462 TI - Time trends of physical activity and television viewing time in Brazil: 2006 2012. AB - BACKGROUND: Despite recent advances in surveillance of physical activity, data on time trends of physical activity in low and middle-income countries are lacking. This study describes time trends in physical activity and television viewing between 2006 and 2012 among Brazilian adults. METHODS: Data from 371,271 adult participants (18 + years) in the Surveillance System for Risk and Protective Factors for Chronic Illnesses using Telephone Survey (VIGITEL) were analysed. Time trends in leisure-time physical activity (>= 5 days/wk; >= 30 min/day), transportation physical activity (using bicycle or walking for >= 30 minutes per day as a means of transportation to/from work) and proportion of participants spending more than three hours per day watching television were analysed. Annual changes according to sex, age and years of schooling were calculated. RESULTS: There was an increase in leisure-time physical activity from 12.8% in 2006 to 14.9% in 2012 (annual increase of 1.9%; p < 0.001). This increase was more marked in younger participants and those with high-school education. Transportation physical activity decreased 12.9% per year (p < 0.001) from 2006 to 2008 and 5.8% per year from 2009 to 2012 (p < 0.001). The annual decline in television viewing time was 5% (p < 0.001) between 2006 and 2009 and 2% (p = 0.16) between 2010 and 2012. CONCLUSION: National survey data from Brazil indicate that leisure-time physical activity appears to be increasing, while television viewing time appears to be decreasing in recent years. However, transportation physical activity has been declining. These data are important for informing national public health policies. PMID- 25124461 TI - Alteration of lipid profile in subclinical hypothyroidism: a meta-analysis. AB - BACKGROUND: Previous studies yielded controversial results about the alteration of lipid profiles in patients with subclinical hypothyroidism. We performed a meta-analysis to investigate the association between subclinical hypothyroidism and lipid profiles. MATERIAL AND METHODS: We searched PubMed, Cochrane Library, and China National Knowledge Infrastructure articles published January 1990 through January 2014. Dissertation databases (PQDT and CDMD) were searched for additional unpublished articles. We included articles reporting the relationship between subclinical hypothyroidism and at least 1 parameter of lipid profiles, and calculated the overall weighted mean difference (WMD) with a random effects model. Meta-regression was used to explore the source of heterogeneity among studies, and the Egger test, Begg test, and the trim and fill method were used to assess potential publication bias. RESULTS: Sixteen observational studies were included in our analysis. Meta-analysis suggested that the serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and total triglyceride levels were significantly increased in patients with subclinical hypothyroidism compared with euthyroidism individuals; the WMD were 12.17 mg/dl, 7.01 mg/dl, and 13.19 mg/dl, respectively (P<0.001 for all). No significant difference was observed for serum high-density lipoprotein cholesterol (HDL-C). Match strategy was the main source of heterogeneity among studies in TC and LDL-C analysis. Potential publication bias was found in TC and LDL-C analysis by the Egger test or Begg test and was not confirmed by the trim and fill method. CONCLUSIONS: Subclinical hypothyroidism may correlate with altered lipid profile. Previous studies had limitations in the control of potential confounding factors and further studies should consider those factors. PMID- 25124464 TI - Microbial priming of plant and animal immunity: symbionts as developmental signals. AB - The functional similarity between root and gut microbiota, both contributing to the nutrition and protection of the host, is often overlooked. A central mechanism for efficient protection against pathogens is defense priming, the preconditioning of immunity induced by microbial colonization after germination or birth. Microbiota have been recruited several times in evolution as developmental signals for immunity maturation. Because there is no evidence that microbial signals are more relevant than endogenous ones, we propose a neutral scenario for the evolution of this dependency: any hypothetic endogenous signal can be lost because microbial colonization, reliably occurring at germination or birth, can substitute for it, and without either positive selection or the acquisition of new functions. Dependency of development on symbiotic signals can thus evolve by contingent irreversibility. PMID- 25124465 TI - Letter to the editor. PMID- 25124466 TI - Association study of ERbeta, AR, and CYP19A1 genes and MtF transsexualism. AB - INTRODUCTION: The etiology of male-to-female (MtF) transsexualism is unknown. Both genetic and neurological factors may play an important role. AIM: To investigate the possible influence of the genetic factor on the etiology of MtF transsexualism. METHODS: We carried out a cytogenetic and molecular analysis in 442 MtFs and 473 healthy, age- and geographical origin-matched XY control males. The karyotype was investigated by G-banding and by high-density array in the transsexual group. The molecular analysis involved three tandem variable regions of genes estrogen receptor beta (ERbeta) (CA tandem repeats in intron 5), androgen receptor (AR) (CAG tandem repeats in exon 1), and CYP19A1 (TTTA tandem repeats in intron 4). The allele and genotype frequencies, after division into short and long alleles, were obtained. MAIN OUTCOME MEASURES: We investigated the association between genotype and transsexualism by performing a molecular analysis of three variable regions of genes ERbeta, AR, and CYP19A1 in 915 individuals (442 MtFs and 473 control males). RESULTS: Most MtFs showed an unremarkable 46,XY karyotype (97.96%). No specific chromosome aberration was associated with MtF transsexualism, and prevalence of aneuploidy (2.04%) was slightly higher than in the general population. Molecular analyses showed no significant difference in allelic or genotypic distribution of the genes examined between MtFs and controls. Moreover, molecular findings presented no evidence of an association between the sex hormone-related genes (ERbeta, AR, and CYP19A1) and MtF transsexualism. CONCLUSIONS: The study suggests that the analysis of karyotype provides limited information in these subjects. Variable regions analyzed from ERbeta, AR, and CYP19A1 are not associated with MtF transsexualism. Nevertheless, this does not exclude other polymorphic regions not analyzed. PMID- 25124467 TI - Are end-of-life practices in Norway in line with ethics and law? AB - BACKGROUND: End-of-life decisions, including limitation of life prolonging treatment, may be emotionally, ethically and legally challenging. Euthanasia and physician-assisted suicide (PAS) are illegal in Norway. A study from 2000 indicated that these practices occur infrequently in Norway. METHODS: In 2012, a postal questionnaire addressing experience with limitation of life-prolonging treatment for non-medical reasons was sent to a representative sample of 1792 members of the Norwegian Medical Association (7.7% of the total active doctor population of 22,500). The recipients were also asked whether they, during the last 12 months, had participated in euthanasia, PAS or the hastening of death of non-competent patients. RESULTS: Seventy-one per cent of the doctors responded. Forty-four per cent of the respondents reported that they had terminated treatment at the family's request not knowing the patient's own wish, doctors below 50 and anaesthesiologists more often. Anaesthesiologists more often reported to have terminated life-prolonging treatment because of resource considerations. Six doctors reported having hastened the death of a patient the last 12 months, one by euthanasia, one by PAS and four had hastened death without patient request. Male doctors and doctors below 50 more frequently reported having hastened the death of a patient. CONCLUSION: Forgoing life-prolonging treatment at the request of the family may be more frequent in Norway that the law permits. A very small minority of doctors has hastened the death of a patient, and most cases involved non-competent patients. Male doctors below 50 seem to have a more liberal end-of-life practice. PMID- 25124468 TI - Ambient temperature and prevalence of obesity in the Spanish population: The Di@bet.es study. AB - OBJECTIVE: The aim of this study was to examine possible associations between ambient temperature and obesity in the Spanish population using an ecological focus. METHODS: The Di@bet.es study is a national, cross-sectional, population based survey of cardiometabolic risk factors and their association with lifestyle. SAMPLE: 5,061 subjects in 100 clusters. VARIABLES: Clinical, demographic and lifestyle survey, physical examination, and blood sampling. The mean annual temperature ( degrees C) for each study site was collected from the Spanish National Meteorology Agency (1971-2000). RESULTS: The prevalence rates of obesity in the different geographical areas divided according to mean annual temperature quartiles were 26.9% in quartile 1 (10.4-14.5 degrees C), 30.5% in quartile 2 (14.5-15.5 degrees C), 32% in quartile 3 (15.5-17.8 degrees C), and 33.6% in quartile 4 (17.8-21.3 degrees C) (P = 0.003). Logistic regression analyses including multiple socio-demographic (age, gender, educational level, marital status) and lifestyle (physical activity, Mediterranean diet score, smoking) variables showed that, as compared with quartile 1, the odd ratios for obesity were 1.20 (1.01-1.42), 1.35 (1.12-1.61), and 1.38 (1.14-1.67) in quartiles 2, 3, and 4, respectively (P = 0.001 for difference, P < 0.001 for trend). CONCLUSIONS: Our study reports an association between ambient temperature and obesity in the Spanish population controlled for known confounders. PMID- 25124469 TI - Clinical significance of surgical resection for the recurrence of esophageal cancer after radical esophagectomy. AB - BACKGROUND: This study aimed to clarify the clinical significance of surgical resection for recurrent lesions after esophagectomy for esophageal cancer. METHODS: Recurrence was detected in 113 of 365 consecutive patients who underwent surgical resection for esophageal cancer, and some treatment was performed for recurrence in 100 of the 113 patients. The treatments were classified into two groups: chemotherapy and/or radiation with surgery (surgery group, n = 14) and chemotherapy and/or radiation without surgery (no surgery group, n = 86). The outcomes were retrospectively analyzed. RESULTS: Of the 14 patients in the surgery group, 3 underwent repeated resection. Thus, a total of 22 resections were performed for these patients. The resected organs were the lymph nodes in nine patients, the lungs in six patients, local recurrence in two patients, subcutaneous recurrence in two patients, the liver in one patient, the brain in one patient, and the parotid gland in one patient. Among the 22 recurrent cases, 20 involved solitary lesions or multiple lesions located in a small resectable region. When the two groups were compared, the surgery group showed a more favorable prognosis in terms of both survival after esophagectomy (median survival time, 103.3 vs 23.1 months; p = 0.0060) and survival after initial recurrence (92.1 vs 12.2 months; p = 0.0057). CONCLUSIONS: Multimodal treatment provides a significant benefit for patients with recurrence after esophagectomy for esophageal cancer. Surgical intervention should be aggressively included in the treatment strategy when the recurrent lesion is solitary or localized. PMID- 25124470 TI - Diagnostic performance of multidetector row computed tomography for assessment of lymph node metastasis in patients with distal rectal cancer. AB - BACKGROUND: The accurate preoperative diagnosis of depth of tumor invasion and nodal status in distal rectal cancer is important because neoadjuvant chemotherapy or lateral pelvic lymph node dissection is indicated for patients with T3-T4 tumor or nodal involvement. This study aimed to determine the optimal cutoff value for predicting lymph node metastasis in patients with distal rectal cancer using multidetector row computed tomography (MDCT). METHODS: The study investigated 77 patients who had undergone surgery for distal rectal cancer at a single institution between 2008 and 2011. Diagnostic performance for depth of tumor invasion and mesorectal and lateral pelvic lymph node metastases was evaluated. The optimal cutoff value was determined by receiver operating characteristic curve analysis. RESULTS: For predicting mesorectal and lateral pelvic lymph node metastasis, MDCT had a sensitivity of 0.36 and 0.89 and a specificity of 0.78 and 0.97, respectively. The optimal cutoff values of major and minor axes lengths for predicting mesorectal lymph node metastasis were 6.5 mm and 5.7 mm, respectively. The areas under the curve (AUCs) were 0.82 and 0.88, respectively. For predicting lateral lymph node metastasis, the optimal cutoff values were 9 mm for the major axis and 6 mm for the minor axis. Both AUCs were 1. CONCLUSIONS: Using MDCT, the optimal cutoff value of minor axis length for predicting mesorectal and lateral pelvic lymph node metastases in patients with distal rectal cancer was 6 mm. The accuracy of MDCT was satisfactory for predicting lateral pelvic lymph node metastasis. PMID- 25124471 TI - Intraperitoneal chemotherapy at the time of surgery is not associated with increased 30-day morbidity and mortality following colorectal resection. AB - BACKGROUND: In the absence of large randomized trials, the independent contribution of intraperitoneal chemotherapy (IPC) to morbidity and mortality (M+M) from cytoreductive surgery remains uncertain. In a multi-institutional cohort of colorectal surgery patients, we examined the association between M+M and the use of IPC. METHODS: Patients undergoing an open colorectal resection for cancer with and without administration of IPC were identified using the American College of Surgeons National Surgical Quality Improvement Program database (2005 2012). Multivariate logistic regression identified factors associated with 30-day M+M. Using a propensity score matching method, patients undergoing IPC were matched 1:3 to non-IPC patients. M+M within the matched cohort was compared using the chi (2) test. RESULTS: Of the 33,912 patients identified, 188 had concurrent IPC. The M+M rates were 41 and 30 % with and without IPC, respectively (p = 0.002). In multivariate analysis, IPC was not associated with M+M (odds ratio 0.92; p = 0.62). Using a propensity score match to control for patient and operative factors, patients who received IPC (n = 188) were matched to patients who did not receive IPC (n = 365). The M+M rates in the matched cohort did not significantly differ (41 % with IPC and 45 % without IPC; p = 0.34). Similarly, mortality (1.1 vs. 2.5 %; p = 0.26) and length of stay (12 vs. 11 days; p = 0.27) were not affected by IPC status. CONCLUSIONS: After controlling for patient and operative factors, IPC was not associated with increased M+M following colorectal resection. The high morbidity observed in patients receiving IPC appears to be driven by operative factors other than the use of IPC. PMID- 25124472 TI - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis. AB - BACKGROUND: Due to the increased adoption of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients with malignant peritoneal mesothelioma (MPM) have seen improved outcomes. We aimed to evaluate and synthesize the recent published literature. METHODS: The review was conducted according to the recommendation of the Meta-Analysis of Observational Studies in Epidemiology group with prespecified inclusion and exclusion criteria. The DEALE method was used to combine mortality rates, and imputation techniques were used to calculate standard errors. Meta-regression techniques were used to synthesize data. Publication bias was assessed using funnel plots. RESULTS: Of 6,528 citations collected, 20 articles reporting on 1,047 patients were included in the analysis. The median age was 51 years (interquartile range 49-55), with 59 % (54 67) female. The median peritoneal carcinomatosis index score was 19 (16-23). Complete cytoreduction (CC0, 1) was performed in 67 % (46-93 %) of patients. Pooled estimates of survival yielded a 1-, 3- and 5-year survival of 84, 59, and 42 %, respectively. Patients receiving early postoperative intraperitoneal chemotherapy [EPIC] (44 %) and those receiving cisplatin intraperitoneal chemotherapy alone (48 %) or in combination (44 %) had an improved 5-year survival. CONCLUSIONS: While CRS + HIPEC has led to an improved survival for patients with MPM compared to historic data, heterogeneity of studies precludes generalizable inferences. EPIC chemotherapy and cisplatin chemoperfusion may infer survival benefit. PMID- 25124460 TI - The Babesia bovis gene and promoter model: an update from full-length EST analysis. AB - BACKGROUND: Babesia bovis is an apicomplexan parasite that causes babesiosis in infected cattle. Genomes of pathogens contain promising information that can facilitate the development of methods for controlling infections. Although the genome of B. bovis is publically available, annotated gene models are not highly reliable prior to experimental validation. Therefore, we validated a preproposed gene model of B. bovis and extended the associated annotations on the basis of experimentally obtained full-length expressed sequence tags (ESTs). RESULTS: From in vitro cultured merozoites, 12,286 clones harboring full-length cDNAs were sequenced from both ends using the Sanger method, and 6,787 full-length cDNAs were assembled. These were then clustered, and a nonredundant referential data set of 2,115 full-length cDNA sequences was constructed. The comparison of the preproposed gene model with our data set identified 310 identical genes, 342 almost identical genes, 1,054 genes with potential structural inconsistencies, and 409 novel genes. The median length of 5' untranslated regions (UTRs) was 152 nt. Subsequently, we identified 4,086 transcription start sites (TSSs) and 2,023 transcriptionally active regions (TARs) by examining 5' ESTs. We identified ATGGGG and CCCCAT sites as consensus motifs in TARs that were distributed around 50 bp from TSSs. In addition, we found ACACA, TGTGT, and TATAT sites, which were distributed periodically around TSSs in cycles of approximately 150 bp. Moreover, related periodical distributions were not observed in mammalian promoter regions. CONCLUSIONS: The observations in this study indicate the utility of integrated bioinformatics and experimental data for improving genome annotations. In particular, full-length cDNAs with one-base resolution for TSSs enabled the identification of consensus motifs in promoter sequences and demonstrated clear distributions of identified motifs. These observations allowed the illustration of a model promoter composition, which supports the differences in transcriptional regulation frameworks between apicomplexan parasites and mammals. PMID- 25124473 TI - FOXC1 is a critical mediator of EGFR function in human basal-like breast cancer. AB - BACKGROUND: Human basal-like breast cancer (BLBC) has a poor prognosis and is often identified by expression of the epidermal growth factor receptor (EGFR). BLBC remains a major clinical challenge because its pathogenesis is not well understood, thus hindering efforts to develop targeted therapies. Recent data implicate the forkhead box C1 (FOXC1) transcription factor as an important prognostic biomarker and functional regulator of BLBC, but its regulatory mechanism and impact on BLBC tumorigenesis remain unclear. METHODS: The association between FOXC1 and EGFR expression in human breast cancer was examined by immunohistochemistry in formalin-fixed tissues and analysis of the TCGA database. The regulation of FOXC1 by EGFR activation was investigated in MDA-MB 468 cells using immunoblotting, qRT-PCR, and luciferase activity assays. This EGFR effect on FOXC1 expression was confirmed using the MDA-MB-468 xenograft model. RESULTS: Both FOXC1 mRNA and protein levels significantly correlated with EGFR expression in human breast tumors. EGFR activation induced FOXC1 transcription through the ERK and Akt pathways in BLBC. EGFR inhibition in vivo reduced FOXC1 expression in xenograft tumors. We also found that FOXC1 knockdown impaired the effects of EGF on BLBC cell proliferation, migration, and invasion. CONCLUSIONS: Our findings uncover a novel EGFR-FOXC1 signaling axis critical for BLBC cell functions, supporting the notion that intervention in the FOXC1 pathway may provide potential modalities for BLBC treatment. PMID- 25124475 TI - The impact of a pulsing groundwater table on greenhouse gas emissions in riparian grey alder stands. AB - Floods control greenhouse gas (GHG) emissions in floodplains; however, there is a lack of data on the impact of short-term events on emissions. We studied the short-term effect of changing groundwater (GW) depth on the emission of (GHG) carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) in two riparian grey alder (Alnus incana) stands of different age in Kambja, southern Estonia, using the opaque static chamber (five replicates in each site) and gas chromatography methods. The average carbon and total nitrogen content in the soil of the old alder (OA) stand was significantly higher than in the young alder (YA) stand. In both stands, one part was chosen for water table manipulation (Manip) and another remained unchanged with a stable and deeper GW table. Groundwater table manipulation (flooding) significantly increases CH4 emission (average: YA-Dry 468, YA-Manip 8,374, OA-Dry 468, OA-Manip 4,187 MUg C m(-2) h(-1)) and decreases both CO2 (average: OA-Dry 138, OA-Manip 80 mg C m(-2) h(-1)) and N2O emissions (average: OA-Dry 23.1, OA-Manip 11.8 MUg N m(-2) h(-1)) in OA sites. There was no significant difference in CO2 and CH4 emissions between the OA and YA sites, whereas in OA sites with higher N concentration in the soil, the N2O emission was significantly higher than at the YA sites. The relative CO2 and CH4 emissions (the soil C stock-related share of gaseous losses) were higher in manipulated plots showing the highest values in the YA-Manip plot (0.03 and 0.0030 % C day( 1), respectively). The soil N stock-related N2O emission was very low achieving 0.000019 % N day(-1) in the OA-Dry plot. Methane emission shows a negative correlation with GW, whereas the 20 cm depth is a significant limit below which most of the produced CH4 is oxidized. In terms of CO2 and N2O, the deeper GW table significantly increases emission. In riparian zones of headwater streams, the short-term floods (e.g. those driven by extreme climate events) may significantly enhance methane emission whereas the long-term lowering of the groundwater table is a more important initiator of N2O fluxes from riparian gley soils than flood pulses. PMID- 25124474 TI - Distribution of PCDD/Fs in the fly ash and atmospheric air of two typical hazardous waste incinerators in eastern China. AB - Distribution of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) in the fly ash and atmospheric air of one medical waste incinerator (MWI) and one industrial hazardous waste incinerator (IHWI) plants were characterized. The PCDD/F concentrations of the stack gas (fly ash) produced from MWI and IHWI were 17.7 and 0.7 ng international toxic equivalent (I-TEQ)/Nm(3) (4.1 and 2.5 ng I-TEQ/g), respectively. For workplace air, the total concentrations of PCDD/Fs were 11.32 and 0.28 pg I-TEQ/Nm(3) (819.5 and 15.3 pg/Nm(3)). We assumed that the large differences of PCDD/F concentrations in workplace air were due to the differences in chlorine content of the waste, combustion conditions, and other contamination sources. With respect to the homologue profiles, the concentrations of PCDFs decreased with the increase of the substituted chlorine number for each site. Among all of the PCDD/F congeners, 2,3,4,7,8-PeCDF was the most important contributor to the I-TEQ value accounting for ca. 43 % of two sites. The gas/particle partition of PCDD/Fs in the atmosphere of the workplace in the MWI was also investigated, indicating that PCDD/Fs were more associated in the particle phase, especially for the higher chlorinated ones. Moreover, the ratio of the I-TEQ values in particle and gas phase of workplace air was 11.0. At last, the relationship between the distribution of PCDD/Fs in the workplace air and that from stack gas and fly ash was also analyzed and discussed. The high correlation coefficient might be a sign for diffuse gas emissions at transient periods of fumes escaping from the incinerator. PMID- 25124476 TI - Recent insights into the biology of neuroblastoma. AB - Neuroblastoma (NB) is an embryonal tumor of the sympathetic nervous system which accounts for 8-10% of pediatric cancers. It is characterized by a broad spectrum of clinical behaviors from spontaneous regression to fatal outcome despite aggressive therapies. Considerable progress has been made recently in the germline and somatic genetic characterization of patients and tumors. Indeed, predisposition genes that account for a significant proportion of familial and syndromic cases have been identified and genome-wide association studies have retrieved a number of susceptibility loci. In addition, genome-wide sequencing, copy-number and expression studies have been conducted on tumors and have detected important gene modifications, profiles and signatures that have strong implications for the therapeutic stratification of patients. The identification of major players in NB oncogenesis, including MYCN, ALK, PHOX2B and LIN28B, has enabled the development of new animal models. Our review focuses on these recent advances, on the insights they provide on the mechanisms involved in NB development and their applications for the clinical management of patients. PMID- 25124477 TI - Anterolateral thigh adipofascial flap in mucosal reconstruction. AB - IMPORTANCE: This study describes a reliable technique for mucosal reconstruction of large defects using components of a common free flap technique. OBJECTIVE: To review the harvest technique and the varied scenarios in which the anterolateral thigh adipofascial flap (ALTAF) can be used for mucosal restoration in oral cavity and nasal reconstruction. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of the medical records of 51 consecutive patients was conducted. The patients had undergone ALTAF head and neck reconstruction between January 2009 and June 2013. Each case was reviewed, and flap survival and goal oriented results were evaluated. RESULTS: Thirty patients met the inclusion criteria and were included in the analysis. The mean patient age was 60.6 years. Reconstruction sites included the tongue, palate, gingiva, floor of the mouth, and nasal mucosa. All mucosal reconstructions maintained function and form of replaced and preserved tissues. One patient (3%) experienced flap failure that was reconstructed with a contralateral adipofascial flap with excellent outcome. Three patients (10%) required minor flap revisions. There were no other complications. CONCLUSIONS AND RELEVANCE: The ALTAF is a versatile flap easily harvested for use in several types of mucosal reconstructions. PMID- 25124478 TI - Flavor-enhancing properties of mushrooms in meat-based dishes in which sodium has been reduced and meat has been partially substituted with mushrooms. AB - The effects of beef substitution with crimini or white mushrooms (Agaricus bisporus) on the flavor profiles of carne asada and beef taco blends were measured with a descriptive analysis panel. Sensory mitigation of sodium reduction through the incorporation of mushrooms was also investigated in the taco blends. The substitution of beef with mushrooms in the carne asada did not alter the overall flavor strength of the dish, but the incorporation of 50% or 80% ground mushroom in the beef taco blend did enhance its overall flavor as well as mushroom, veggie, onion, garlic and earthy flavors, and umami and sweet tastes. Overall flavor intensity of the 25% reduced-salt version of the 80% mushroom taco blend matched that of the full-salt versions of the 100% and 50% beef formulations, thus indicating that the substitution of 80% of the meat with mushrooms did mitigate the 25% sodium reduction in terms of the overall flavor impact of the dish, even if it did not quite compensate for the reduction in salty taste. This proof-of-concept study for the Healthy Flavors Research Initiative indicates that because of their flavor-enhancing umami principles, mushrooms can be used as a healthy substitute for meat and a mitigating agent for sodium reduction in meat-based dishes without loss of overall flavor. PMID- 25124479 TI - The relation between FoxP3+ regulatory T cells and fungal density in oral paracoccidioidomycosis: a preliminary study. AB - Regulatory T (Treg) cells may play an important role in the pathogenesis of paracoccidioidomycosis (PCM), but data on the role of Treg cells in the context of oral PCM are still scarce. The objectives of this study were to investigate the density of FoxP3(+) T regulatory cells in oral PCM and to correlate the results with the density of Paracoccidioides brasiliensis in the lesions. Cases of chronic oral PCM seen between 2000 and 2008 were included in this study. The diagnosis of all lesions was confirmed with histopathological examination and Grocott-Gomori staining. The quantitative analysis of the viable fungi was conducted in all cases with Grocott-stained slides. Treg cells were identified using antibodies against FoxP3. Pearson correlation coefficient was used to test the correlation between the density of fungi and Treg cells. Results were considered significant when P < 0.05. A total of 11 cases of oral PCM were obtained. There was a positive correlation between fungal density and FoxP3(+) Treg cells density in oral lesions, however, without statistical significance. A positive relation between Treg cells and fungal density was seen in oral PCM. Further studies are required to further elucidate the role of these cells in the pathogenesis of oral PCM, as well the clinical significance of these findings. PMID- 25124480 TI - The Segond fracture: a bony injury of the anterolateral ligament of the knee. AB - PURPOSE: The purpose of this study was to investigate the relation of the Segond fracture with the anterolateral ligament (ALL) of the knee. METHODS: To identify the soft-tissue structure causative for the Segond fracture, a study was set up to compare anatomic details of the tibial insertion of the recently characterized ALL in cadaveric knees (n = 30) with radiologic data obtained from patients (n = 29) with a possible Segond fracture based on an imaging protocol search. The spatial relation of the ALL footprint with well-identifiable anatomic landmarks at the lateral aspect of the knee was determined, and this was repeated for the Segond fracture bed. RESULTS: In all of the included cadaveric knees, a well defined ALL was found as a distinct ligamentous structure connecting the lateral femoral epicondyle with the anterolateral proximal tibia. The mean distance of the center of the tibial ALL footprint to the center of the Gerdy tubercle (GT ALL distance) measured 22.0 +/- 4.0 mm. The imaging database search identified 26 patients diagnosed with a Segond fracture. The mean GT-Segond distance measured 22.4 +/- 2.6 mm. The observed difference of 0.4 mm (95% confidence interval, -1.5 to 2.2 mm) between the GT-ALL distance and GT-Segond distance was neither statistically significant (P = .70) nor clinically relevant. CONCLUSIONS: The results of this study confirmed the hypothesis that the ALL inserts in the region on the proximal tibia from where Segond fractures consistently avulse, thus suggesting that the Segond fracture is actually a bony avulsion of the ALL. CLINICAL RELEVANCE: Although the Segond fracture remains a useful radiographic clue for indirect detection of anterior cruciate ligament injuries, the Segond fracture should be considered a frank ligamentous avulsion itself. PMID- 25124481 TI - Transtibial versus anteromedial portal anterior cruciate ligament reconstruction using soft-tissue graft and expandable fixation. AB - PURPOSE: To compare clinical outcomes between transtibial drilling and anteromedial portal techniques for anterior cruciate ligament (ACL) reconstruction using soft-tissue grafts secured with expandable fixation. METHODS: Patients undergoing soft-tissue ACL reconstruction using expandable fixation between 2007 and 2011 were reviewed for inclusion in this study. Revision ACL cases were excluded. All surgeries were performed by 1 of 2 sports medicine fellowship-trained surgeons (T.S.D., K.D.M.). A total of 128 patients (67 comprising transtibial cohort and 61 comprising anteromedial portal cohort) had a minimum of 24 months' follow-up (mean, 27 months) and met the inclusion criteria. The patients were divided into 2 groups based on the method used for creation of the femoral tunnel. At final follow-up, outcomes were assessed with KT-1000 (MEDmetric, San Diego, CA) measurements, as well as International Knee Documentation Committee, Lysholm, and Tegner scores. Data were screened for normality and skew before use of parametric statistics and were transformed if necessary. Data were analyzed by 1-way analysis of variance with post hoc paired comparisons using the Bonferroni approximation. RESULTS: No differences in demographic characteristics were observed between the 2 groups. There was no significant difference in postoperative KT-1000 measurements between the 2 cohorts (1.571 +/- 0.2275 mm in transtibial cohort [n = 35] and 1.246 +/- 0.09249 mm in anteromedial cohort [n = 61], P = .1259). A significant improvement in International Knee Documentation Committee scores was observed in the anteromedial cohort, increasing from 41 +/- 16 to 89 +/- 7.4 (mean +/- SD) (P < .0001). Similar changes were observed for the Lysholm score. There was no significant difference between cohorts for any postoperative scores measured (P > .2). CONCLUSIONS: Our data show comparable KT-1000 measurements for both anteromedial and transtibial femoral drilling techniques when using a soft-tissue graft with expandable fixation. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 25124482 TI - International knee documentation committee knee survey use after anterior cruciate ligament reconstruction: a 2005-2012 systematic review and world region comparison. AB - PURPOSE: The purpose of this review was to evaluate International Knee Documentation Committee (IKDC) survey use after anterior cruciate ligament reconstruction compared with other surveys and determine evidence levels and methodologic study quality by world region. METHODS: The Medline database was searched from January 2005 through December 2012. RESULTS: We identified 421 studies and 33 surveys. Europe and Australia had more objective and subjective IKDC form use (chi(2) = 9.6, P = .047). Europe and Asia had more objective IKDC form use (chi(2) = 19.4, P = .001). Asia had more Lysholm knee scale use (chi(2) = 29.9, P < .0001). Europe had more Tegner Activity Level scale (chi(2) = 31.7, P < .0001) and Knee Injury and Osteoarthritis Outcome Score (chi(2) = 20.5, P < .0001) use. North America and Australia had more Cincinnati or Noyes knee rating scale use (chi(2) = 21, P < .0001). Asia and Australia had more studies with greater than 60 subjects (chi(2) = 24.4, P = .018). Europe had more studies with greater than 24 months' follow-up (chi(2) = 18.4, P = .018). Asia had more studies with adequate surgical descriptions (chi(2) = 33.2, P < .0001). North America had more studies with well-described rehabilitation (chi(2) = 18.2, P = .02). Europe had more studies with confirmed recruitment (chi(2) = 12.9, P = .012). Australia and North America had more studies with confirmed independent investigators (chi(2) = 11.1, P = .026). Europe had more studies with greater than 80% recruitment (chi(2) = 16.0, P = .04). Methodologically stronger studies used the objective IKDC survey (P < .0001), the objective and subjective IKDC survey (P = .002), or the Cincinnati or Noyes scale (P = .002). This group also made greater use of the Tegner scale (P = .013). CONCLUSIONS: Objective and subjective IKDC form use is comparable with Lysholm and Tegner scale use. Objective and subjective IKDC form use in combination with the Tegner Activity Level scale is recommended. LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies. PMID- 25124483 TI - Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder: an update. AB - Several million children and a growing number of adults are currently being treated for attention-deficit hyperactivity disorder (ADHD) worldwide. Concerns have been expressed about possible cardiac effects of the common treatments, namely methylphenidate, amphetamines and atomoxetine. Small increases in mean heart rate (HR) and mean blood pressure (BP) have been reported for all three drugs, but most of the studies have not yielded statistically significant results. These studies also have limitations, particularly regarding the lack of accepted and standardised measurement methods. Several large studies of the very rare phenomenon of sudden death in children have failed to show any convincing association with ADHD treatment. Whether minor increases in HR and BP have a cumulative effect over many years and have a long-term adverse effect on cardiovascular health remains undetermined. PMID- 25124484 TI - Ciona intestinalis NADH dehydrogenase NDX confers stress-resistance and extended lifespan on Drosophila. AB - An assembled cDNA coding for the putative single-subunit NADH dehydrogenase (NDX) of Ciona intestinalis was introduced into Drosophila melanogaster. The encoded protein was found to localize to mitochondria and to confer rotenone-insensitive substrate oxidation in organello. Transgenic flies exhibited increased resistance to menadione, starvation and temperature stress, and manifested a sex and diet dependent increase in mean lifespan of 20-50%. However, NDX was able only weakly to complement the phenotypes produced by the knockdown of complex I subunits. PMID- 25124486 TI - [Invasive pneumococcal disease in the Community of Valencia. Six years of surveillance (2007-2012)]. AB - INTRODUCTION: The introduction of conjugated anti-pneumonia vaccines has led to a change in the epidemiology of Invasive Pneumococcal Disease (IPD). The aim of this study is to describe the trends in IPD in the Community of Valencia during the period 2007-2012. MATERIAL AND METHODS: A retrospective, descriptive and longitudinal study was conducted on IPD in the Community of Valencia during the period 2007-2012, The information sources used were the Epidemiological Surveillance Analysis (Analisis de la Vigilancia Epidemiologica (AVE)) and the Valencian Microbiology Network (Red Microbiologica Valenciana (RedMIVA)) of the Valencia Health Department. RESULTS: The incidence of IPD decreased between 2007 and 2012 in all age groups, mainly in the under 5 year-olds, dropping from 30.5 cases to 12.3 cases per 10(5) inhabitants (p< .001). Pneumonia was the principal presentation of the disease, with a decrease in its rates from 6.9 to 4.1 cases per 10(5) inhabitants (p< .001). A gradual, non-significant, reduction from 26% to 12% (p=.23) was observed in the proportion of cases due to the serotypes contained in the heptavalent vaccine (PCV7), mainly in the under 5 year-olds. The cases due to additional serotypes in 13-valent conjugated vaccine (1, 3, 5, 6A, 7F and 19A) also showed a decreasing trend, mainly in vaccinated under 5 year olds (52.6% vs 14.3%; p=.03), while the cases due to non-vaccine serotypes significantly increased from 42.3% to 56.7% in the general population (p=.002), and from 47.4% to 78.6% in vaccinated under 5 year-olds (p=.08). CONCLUSIONS: The results of this study show a reduction in the incidence of IPD, with a decrease in the proportion of cases produced by vaccine serotypes, and an increase in the proportion of those not vaccinated. Epidemiological Surveillance is necessary to monitor the trends in the disease. PMID- 25124485 TI - A multicentre sero-behavioural survey for hepatitis B and C, HIV and HTLV among people who inject drugs in Germany using respondent driven sampling. AB - BACKGROUND: People who inject drugs are at high risk for hepatitis B, hepatitis C and HIV. HTLV was reported by neighboring countries to be prevalent in this population, but the situation for Germany is unclear. To generate seroprevalence and related behavioural data and to enhance prevention efforts against these infections for drug users in Germany, a multicentre sero- and behavioural survey was initiated. People who inject drugs are not well reached by services for testing and counselling for blood-borne infections in Germany. An interventional part of the study is intended to prove feasibility and acceptance of testing and counselling in low-threshold drop-in settings. METHODS/DESIGN: Between May 2011 and March 2015, eligible participants (persons having injected drugs within the last 12 months, aged 16 years+, and living in the study city) are recruited by respondent driven sampling, using low-threshold drop-in facilities as study-sites in eight German cities with large drug scenes. Calculated sample size is 2,033 participants. Capillary blood samples collected as dried blood spots are anonymously tested for serological and molecular markers of hepatitis B and C, HIV, and HTLV I and II. A detailed face-to-face-interview about hepatitis- and HIV-related knowledge, former testing, imprisonment, sexual and injecting risk behaviour is conducted with participants. Staff is trained to offer pre- and post test-counselling of blood-borne infections and HIV rapid testing to participants. DISCUSSION: We chose respondent driven sampling for recruitment of participants to improve representativeness of results. Persons, who are not reached by the facility where the study is conducted, are aimed to be included by recruitment through their personal social network of injecting drug users. To reduce differential biases in the questions on knowledge of transmission and prevention of infections, we present true statements on hepatitis B, C and HIV, their possible routes of transmission and measures of prevention to participants. Participants are told that the statements are true and are asked to answer if they knew this fact already or if it is new to them. In case of knowledge gaps they are offered free targeted counselling as well as free HIV rapid testing and post-test counselling of HIV and hepatitis test results. PMID- 25124487 TI - [Does the prescribing of antibiotics in paediatrics improve after a multidisciplinary intervention?]. AB - Antibiotics overuse is linked to elevated antimicrobial resistance. In Aragon, Spain, the highest antibiotic prescription rates occur among children from 1 to 4 years old. The rate of use in this age group is over 60%. AIM: To evaluate the effect of multi-faceted intervention on Primary Care paediatricians to reduce antibiotic use and to improve antibiotic prescribing for paediatric outpatients. METHODS: Outpatient antimicrobial prescribing was analysed before and after an intervention in paediatricians. The intervention included a clinical education session about diagnosis and treatment in the most prevalent paediatric infectious diseases, a clinical interview and communication skills, a workshop on rapid Streptococcus antigen detection test and patient information leaflets and useful internet websites for parents. The control group included paediatricians without this educational intervention on antibiotics. RESULTS: Antibiotic prescribing decreased from 19.17 defined daily doses per 1000 inhabitants/day (DID) to 14.36 DID among intervention paediatricians vs 19.84 DID to 16.02 DID in controls. The decreasing was higher in the intervention group, but the effect was not statistically significant. Macrolides and broad-spectrum penicillins prescribing decreased in both groups. CONCLUSION: Antibiotic prescribing decreased, but there were no statistically significant differences between the two groups. The high satisfaction of paediatricians in the intervention group makes it necessary to continue with these kinds of strategies to improve antibiotic use in outpatients. PMID- 25124488 TI - [Procedure for the marketing authorization of an antibacterial agent]. AB - The marketing authorization of a new medicinal product is the first step before being placed on the market, and includes the full investigation programme. In order to ensure their quality, safety and efficacy, medicinal products are closely regulated from their initial phases of investigation to their use in clinical practice. For registration purposes, the results of all the clinical and preclinical studies, along with quality data and the description of the manufacturing process should be submitted. All information collected is presented for review by the competent authority. The European Medicines Agency regulates the registration of medicines in Europe, and national agencies in each EU member state are responsible for the assessment of the marketing authorisation application. To facilitate the development of clinical programmes, there is a common framework for the evaluation of an antibacterial, which includes guidelines and an addendum, detailing the specific requirements that must be carried out in clinical trials to assess the efficacy and safety for most of the infections. PMID- 25124490 TI - Beneficial effect of Oligonol supplementation on sweating response under heat stress in humans. AB - Oligonol is a low-molecular weight polyphenol that possesses antioxidant and anti inflammatory properties. However, nothing is known regarding the impact of Oligonol on sudomotor activity. This study investigated the effects of Oligonol supplementation on sudomotor activity during heat load in humans. Initially, we conducted a placebo-controlled, cross-over trial where participants took a daily dose of Oligonol 200 mg or placebo for one week. After a 2 week washout period, the subjects were switched to the other study arm. As a heat load, half-body immersion into hot water (42 +/- 0.5 degrees C for 30 min) was performed in an automated climate chamber. Tympanic and skin temperatures were measured. Sudomotor activity, including onset time, sweat rate (SR) and volume (SV), active sweat gland density (ASGD), and sweat gland output (SGO), was tested in four or eight areas of skin. When compared with placebo, Oligonol attenuated increases in tympanic and skin temperatures after the heat load. There was an increasing trend in local sweat onset time, but there was a decrease in local SR, SV, ASGD, and SGO for Oligonol compared to placebo. The mean ASGD was significantly higher in the Oligonol group than in the placebo group for 10, 20, and 30 min. This study demonstrates that Oligonol appears to be worthy of consideration as a natural supplement to support more economical use of body fluids against heat stress. PMID- 25124489 TI - [Acute outbreak of hepatitis C in human immunodeficiency virus-infected patients]. AB - BACKGROUND: Recent studies suggest an increased incidence of acute infection with hepatitisC virus (AHC) in men who have sex with men (MSM) co-infected with HIV. Early treatment with interferon-alpha, alone or in combination with ribavirin, significantly reduces the risk of chronic evolution. METHODS: This retrospective study includes all HIV patients with AHC in our centre from 2003 to March 2013. AHC was defined by seroconversion of HCV antibodies and detection of serum HCV RNA. RESULTS: 93 episodes of AHC were diagnosed in 89 patients. All but three were MSM with a history of unprotected sex. Thirty-seven (40%) patients had other associated sexually transmitted disease. The 29% (27) had any symptoms suggestive of AHC. HCV genotype 4 was the most common (41%), followed by genotype1. Seventy patients started treatment with interferon-alfa and weight-adjusted ribavirin. Currently 46 have completed treatment and follow-up, reaching 26 of them (56.5%) sustained viral response. CONCLUSIONS: The incidence of AHC in HIV MSM patients from our centre has increased exponentially in recent years; sexual transmission remains the main route of infection. Early treatment with interferon-alpha and ribavirin achieved a moderate response in these patients. PMID- 25124491 TI - Monitoring fetal immune development in human pregnancies: current concepts and future goals. AB - The vast majority of the current knowledge on immune development in the fetal period has been gained from animal studies, particularly from mouse models. This has led to a great improvement in our current understanding of immune ontogeny. However, it has also become clear that in many ways the mouse model of pregnancy differs from the situation in human pregnancy, such as the degree and importance of trophoblast invasion, the kind of MHC class repertoire of the extravillous trophoblast cells, and differences concerning the development and regulation of T cells. It will be of paramount importance to develop non-invasive screening methods to assess fetal immune development in humans. The focus of this mini review is to discuss how prenatal ultrasound evaluation can be used as a tool to monitor fetal immune development in human pregnancies. To identify the fetuses at risk of immune disorders could be the first step to developing prevention strategies in the future. PMID- 25124498 TI - Seclusion and restraint as measures of the quality of hospital care: any exceptions? AB - The Joint Commission has recently included seclusion and restraint as quality-of care indicators for hospital-based inpatient psychiatric services. Their inclusion is the result of abuse of these practices, wide variation across hospitals, and cultural influences, including the consumer and recovery movements. Over the next few years, these indicators will increasingly influence treatment modalities available to hospitalized patients. This Open Forum provides a brief history of changing attitudes toward use of seclusion and restraint. It describes three clinical scenarios that highlight appropriate and humane use of seclusion and restraint and that illustrate the clinical complexities associated with their use. Potential unforeseen consequences of the reduction or elimination of seclusion and restraint are described. PMID- 25124495 TI - Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study. AB - BACKGROUND: Although omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce coronary heart disease (CHD), controversy remains about benefits versus harms, including concerns over theorized proinflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid (the major dietary PUFA), gamma-linolenic acid, dihomo-gamma linolenic acid, and arachidonic acid, with total and cause-specific mortality in the Cardiovascular Health Study, a community-based U.S. cohort. METHODS AND RESULTS: Among 2792 participants(aged >=65 years) free of cardiovascular disease at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34 291 person-years of follow up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher linoleic acid was associated with lower total mortality, with extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely attributable to cardiovascular disease causes, especially nonarrhythmic CHD mortality (hazard ratio, 0.51; 95% confidence interval, 0.32-0.82; P trend=0.001). Circulating gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid were not significantly associated with total or cause-specific mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard ratio was 0.97; 95% confidence interval, 0.70-1.34; P trend=0.87). Evaluated semiparametrically, linoleic acid showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both. CONCLUSIONS: High circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults. PMID- 25124497 TI - Maintenance of the nutritional prognostic index predicts survival in patients with unresectable metastatic colorectal cancer. AB - PURPOSE: Nutrition and immunity significantly affect the progression of cancer in cancer patients. Therefore, the evaluation of the nutritional and immune status would be useful as a prognostic factor and to determine the optimal treatment strategy for patients with unresectable metastatic colorectal cancer who are receiving chemotherapy. The aim of this retrospective study was to evaluate the prognostic significance of the nutritional and immune status in patients with unresectable metastatic colorectal cancer treated with chemotherapy. METHODS: We retrospectively reviewed 80 patients with colorectal cancer. A total of 22 patients had metachronous unresectable cancer, and 58 patients had synchronous unresectable cancer. All patients underwent combination chemotherapy with oxaliplatin or irinotecan plus 5-fluorouracil/leucovorin as first-line chemotherapy. We then examined the correlations between the Onodera's prognostic nutritional index (OPNI) and the patients' clinicopathological features. The OPNI was calculated as follows: 10 * serum albumin (g/dl) + 0.005 * total lymphocyte count (per mm(3)). According to the receiver operating characteristic (ROC) curve analysis, the cutoff value for OPNI was 44.5. RESULTS: Patients with a pretreatment OPNI of ?44.5 demonstrated a longer OS than those with a pretreatment OPNI of <44.5. Moreover, we categorized these patients into four groups according to the combination of the pre- and post-treatment OPNI. The patients in the group with both OPNIs >=44.5 exhibited a better prognosis compared to the other group (p = 0.001). CONCLUSION: The OPNI is considered to be a useful marker for predicting the long-term outcome in patients who receive chemotherapy for unresectable metastatic colorectal cancer. PMID- 25124499 TI - Exploring the genome-wide relation between copy number status and microRNA expression. AB - The deregulation of miRNAs has been associated with several different cancer types. Deregulation occurs in several ways, but generally little is known about the basis for the distorted expression of miRNAs. We investigated the relation between copy number status and miRNA expression at the genome-wide level using cytogenetic and array-based methods to characterize genomic aberrations in hematopoietic cell lines. For the same cell lines, we obtained global miRNA expression profiles, and analyzed the genome-wide correlation using the Spearman's rank test. This analysis showed that the expression of only a two miRNAs (miR-324-5p encoded by MIR324 at 17p13.1 and miR-660 encoded by MIR660 at Xp11.23) was influenced by copy number status. Our data imply that no direct relation between copy number status and miRNA expression exists in the investigated cell lines. PMID- 25124496 TI - Cardiac CaM Kinase II genes delta and gamma contribute to adverse remodeling but redundantly inhibit calcineurin-induced myocardial hypertrophy. AB - BACKGROUND: Ca(2+)-dependent signaling through CaM Kinase II (CaMKII) and calcineurin was suggested to contribute to adverse cardiac remodeling. However, the relative importance of CaMKII versus calcineurin for adverse cardiac remodeling remained unclear. METHODS AND RESULTS: We generated double-knockout mice (DKO) lacking the 2 cardiac CaMKII genes delta and gamma specifically in cardiomyocytes. We show that both CaMKII isoforms contribute redundantly to phosphorylation not only of phospholamban, ryanodine receptor 2, and histone deacetylase 4, but also calcineurin. Under baseline conditions, DKO mice are viable and display neither abnormal Ca(2+) handling nor functional and structural changes. On pathological pressure overload and beta-adrenergic stimulation, DKO mice are protected against cardiac dysfunction and interstitial fibrosis. But surprisingly and paradoxically, DKO mice develop cardiac hypertrophy driven by excessive activation of endogenous calcineurin, which is associated with a lack of phosphorylation at the auto-inhibitory calcineurin A site Ser411. Likewise, calcineurin inhibition prevents cardiac hypertrophy in DKO. On exercise performance, DKO mice show an exaggeration of cardiac hypertrophy with increased expression of the calcineurin target gene RCAN1-4 but no signs of adverse cardiac remodeling. CONCLUSIONS: We established a mouse model in which CaMKII's activity is specifically and completely abolished. By the use of this model we show that CaMKII induces maladaptive cardiac remodeling while it inhibits calcineurin dependent hypertrophy. These data suggest inhibition of CaMKII but not calcineurin as a promising approach to attenuate the progression of heart failure. PMID- 25124500 TI - Psychometric properties of the social phobia and social interaction anxiety scales: evidence of construct equivalence in an African American sample. AB - This study evaluated the psychometric properties of the Social Phobia Scale and Social Interaction Anxiety scale in a community sample of African Americans. We conducted a confirmatory factor analysis of the combined scales comparing the data to 2- and 3-factor solutions commonly reported in the literature. The results indicated that neither solution produce an adequate fit to the data in this study. We then proceeded to conduct an exploratory factor analysis within a confirmatory framework of both scales. While we were able to extract a 2-factor solution from the data, the item composition of the factors was somewhat different for African Americans than what is typically reported in non-Hispanic White samples. While we conclude that use of the two social anxiety scales is warranted, we make recommendations regarding the interpretation of both scales with African Americans. PMID- 25124494 TI - Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation. AB - BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood. METHODS AND RESULTS: To identify new AF-related genes, we used a multifaceted approach, combining large-scale genotyping in 2 ethnically distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and functional validation. Four novel loci were identified in individuals of European descent near the genes NEURL (rs12415501; relative risk [RR]=1.18; 95% confidence interval [CI], 1.13-1.23; P=6.5*10(-16)), GJA1 (rs13216675; RR=1.10; 95% CI, 1.06 1.14; P=2.2*10(-8)), TBX5 (rs10507248; RR=1.12; 95% CI, 1.08-1.16; P=5.7*10( 11)), and CAND2 (rs4642101; RR=1.10; 95% CI, 1.06-1.14; P=9.8*10(-9)). In Japanese, novel loci were identified near NEURL (rs6584555; RR=1.32; 95% CI, 1.26 1.39; P=2.0*10(-25)) and CUX2 (rs6490029; RR=1.12; 95% CI, 1.08-1.16; P=3.9*10( 9)). The top single-nucleotide polymorphisms or their proxies were identified as cis-eQTLs for the genes CAND2 (P=2.6*10(-19)), GJA1 (P=2.66*10(-6)), and TBX5 (P=1.36*10(-5)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted in prolongation of the atrial action potential duration (17% and 45%, respectively). CONCLUSIONS: We have identified 5 novel loci for AF. Our results expand the diversity of genetic pathways implicated in AF and provide novel molecular targets for future biological and pharmacological investigation. PMID- 25124502 TI - Comparison of the Penn State Worry Questionnaire (PSWQ) and abbreviated version (PSWQ-A) in a clinical and non-clinical population of older adults. AB - The Penn State Worry Questionnaire (PSWQ) is a widely used measure of worry severity. An 8-item abbreviated version (PSWQ-A) has been developed as a brief screening measure, although there are limited studies assessing the psychometric properties of this measure in a large geriatric population. The aim of this study was to assess the utility of the PSWQ-A compared to the full PSWQ, to identify pathological worry in an older adult sample (N=108) of clinically anxious and depressed older adults, compared to a non-clinical sample (N=53). The PSWQ and PSWQ-A were found to have similarly adequate reliability and validity. The factor structure of the PSWQ-A was replicated, but not for the PSWQ. Both measures accurately distinguished between clinical and non-clinical status with similar sensitivity and specificity. These findings indicate the PSWQ-A is a useful measure for screening or epidemiological studies assessing worry in geriatric populations. PMID- 25124501 TI - PTSD symptom severity and psychiatric comorbidity in recent motor vehicle accident victims: a latent class analysis. AB - We conducted a latent class analysis (LCA) on 249 recent motor vehicle accident (MVA) victims to examine subgroups that differed in posttraumatic stress disorder (PTSD) symptom severity, current major depressive disorder and alcohol/other drug use disorders (MDD/AoDs), gender, and interpersonal trauma history 6-weeks post MVA. A 4-class model best fit the data with a resilient class displaying asymptomatic PTSD symptom levels/low levels of comorbid disorders; a mild psychopathology class displaying mild PTSD symptom severity and current MDD; a moderate psychopathology class displaying severe PTSD symptom severity and current MDD/AoDs; and a severe psychopathology class displaying extreme PTSD symptom severity and current MDD. Classes also differed with respect to gender composition and history of interpersonal trauma experience. These findings may aid in the development of targeted interventions for recent MVA victims through the identification of subgroups distinguished by different patterns of psychiatric problems experienced 6-weeks post-MVA. PMID- 25124503 TI - Parental changes after involvement in their anxious child's cognitive behavior therapy. AB - OBJECTIVE: Specific parental behaviors and cognitions are associated with child anxiety. Studies informing us of the directionality of the associations are lacking. We investigated the effect of parental involvement in children's anxiety treatment on parental behaviors and cognitions. METHOD: Children (N=54, 7-12 years) and parents were randomly allocated to different treatment groups (involved, not involved). Observed behavior, self-reported behavior and cognitions were assessed separately for mothers and fathers at pre-, posttreatment and follow-up. RESULTS: There were no differences over time for self-reported parental efficacy and observed negativity, but self-reported autonomy granting increased for both groups over time. Differential effects were found between groups for observed paternal over-involvement (fathers involved in treatment showed a more rapid decrease) and self-reported maternal autonomy granting (non-involved mothers showed a greater increase). CONCLUSION: Our findings suggest that child anxiety significantly influences parental behaviors and cognitions. Child therapy may successfully change the family system. PMID- 25124504 TI - Implicit affective evaluation bias in hypochondriasis: findings from the Affect Misattribution Procedure. AB - Cognitive theories of hypochondriasis (HYP) suggest that catastrophic misinterpretations of benign body sensations are a core feature for the maintenance of the disorder. There is tentative support from an analog sample that the interpretation of illness-related information also involves an implicit affective component. This is the first study to examine this negative affective evaluation bias implicitly in patients with HYP. An adapted version of the Affect Misattribution Procedure (AMP) with illness, symptom and neutral primes was used in 80 patients with HYP, and compared to 83 patients with an anxiety disorder (AD), as well as 90 healthy controls (CG). The HYP group showed significantly more negative affective reactions in illness prime trials, compared to both control groups, as well as more negative implicit evaluations on symptom prime trials, compared to the CG. Significant inverse relationships were observed only between the implicit evaluations of illness words and health anxiety questionnaires. Thus, an implicit negative affective evaluation bias of serious illnesses rather than symptoms is a unique feature of HYP. PMID- 25124505 TI - Peeking into the black box: mechanisms of action for anger management treatment. AB - We investigated potential mechanisms of action for anger symptom reductions, specifically, the roles of anger regulation skills and therapeutic alliance on changes in anger symptoms, following group anger management treatment (AMT) among combat veterans with posttraumatic stress disorder (PTSD). Data were drawn from a published randomized controlled trial of AMT conducted with a racially diverse group of 109 veterans with PTSD and anger symptoms residing in Hawaii. Results of latent growth curve models indicated that gains in calming skills predicted significantly larger reductions in anger symptoms at post-treatment, while the development of cognitive coping and behavioral control skills did not predict greater symptom reductions. Therapeutic alliance had indirect effects on all outcomes mostly via arousal calming skills. Results suggest that generalized symptom reduction may be mediated by development of skills in calming physiological arousal. In addition, arousal reduction skills appeared to enhance one's ability to employ other anger regulation skills. PMID- 25124506 TI - The relationship between the alternative exon 7 splice variant of the BF gene and MHC-related Marek's disease resistance in chickens. AB - The study was to analyse the relationship between the alternative exon 7 splice variant of the BF gene and MHC-related Marek's disease (MD) resistance in chickens. The experiment first determined whether or not the cocks of Xiayan chickens have alternative splicing-out of the exon 7 of the BF gene from peripheral blood leucocytes (PBLs). Then, selected two groups: Group K included the offspring of the selected cocks which have no alternative splicing-out of the exon 7 of the BF gene; Group Y included the offspring of the selected cocks which have alternative splicing-out of the exon 7 of the BF gene. All hens used in the cross-breeding were non-selected. The experimental chickens were challenged with a very virulent strain of Marek's disease virus (MDV) at 4 days old and were raised for 12 weeks. At this time, all the surviving chickens were killed and necropsy was also performed during the experiment whenever chickens died from the infection. Tumour incidence and mortality were calculated using SPSS, and the tissues were collected to detect MDV by PCR. The results showed that the mortalities of Group K and Y were 52.75% and 70.65%, respectively; and that the tumour incidences of non-alternative splicing-out of the exon 7 of the BF for Groups K and Y were 15.38% and 38.89%, respectively; the tumour incidences for the alternative splicing-out of the exon 7 were 46.15% and 56.76%, respectively. The results demonstrated the tumour incidence was highly related with the alternative exon 7 splice variant of the BF gene (P < 0.05). PMID- 25124507 TI - Cognitive Risk Factors for Specific Learning Disorder: Processing Speed, Temporal Processing, and Working Memory. AB - High comorbidity rates between reading disorder (RD) and mathematics disorder (MD) indicate that, although the cognitive core deficits underlying these disorders are distinct, additional domain-general risk factors might be shared between the disorders. Three domain-general cognitive abilities were investigated in children with RD and MD: processing speed, temporal processing, and working memory. Since attention problems frequently co-occur with learning disorders, the study examined whether these three factors, which are known to be associated with attention problems, account for the comorbidity between these disorders. The sample comprised 99 primary school children in four groups: children with RD, children with MD, children with both disorders (RD+MD), and typically developing children (TD controls). Measures of processing speed, temporal processing, and memory were analyzed in a series of ANCOVAs including attention ratings as covariate. All three risk factors were associated with poor attention. After controlling for attention, associations with RD and MD differed: Although deficits in verbal memory were associated with both RD and MD, reduced processing speed was related to RD, but not MD; and the association with RD was restricted to processing speed for familiar nameable symbols. In contrast, impairments in temporal processing and visuospatial memory were associated with MD, but not RD. PMID- 25124508 TI - Acid/base switching of the tautomerism and conformation of a dioxoporphyrin for integrated binary subtraction. AB - Compared with most of the reported logic devices based on the supramolecular approach, systems based on individual molecules can avoid challenging construction requirements. Herein, a novel dioxoporphyrin DPH22 was synthesized and two of its tautomers were characterized by single-crystal X-ray diffraction studies. Compound DPH22 exhibits multichannel controllable stepwise tautomerization, protonation, and deprotonation processes through interactions with H(+) and F(-) ions. By using the addition of H(+) and F(-) ions as inputs and UV/Vis absorption values at lambda=412, 510, 562, and 603 nm as outputs, the controlled tautomerism of DPH22 has been successfully used for the construction of an integrated molecular level half-subtractor and comparator. In addition, this acid/base-switched tautomerism is reversible, thus endowing the system with ease of reset and recycling; consequently, there is no need to modulate complicated intermolecular interactions and electron-/charge-transfer processes. PMID- 25124509 TI - Neuroimaging in social anxiety disorder-a meta-analytic review resulting in a new neurofunctional model. AB - Social anxiety disorder (SAD) is one of the most frequent anxiety disorders. The landmark meta-analysis of functional neuroimaging studies by Etkin and Wager (2007) revealed primarily the typical fear circuit as overactive in SAD. Since then, new methodological developments such as functional connectivity and more standardized structural analyses of grey and white matter have been developed. We provide a comprehensive update and a meta-analysis of neuroimaging studies in SAD since 2007 and present a new model of the neurobiology of SAD. We confirmed the hyperactivation of the fear circuit (amygdala, insula, anterior cingulate and prefrontal cortex) in SAD. In addition, task-related functional studies revealed hyperactivation of medial parietal and occipital regions (posterior cingulate, precuneus, cuneus) in SAD and a reduced connectivity between parietal and limbic and executive network regions. Based on the result of this meta-analysis and review, we present an updated model of SAD adopting a network-based perspective. The disconnection of the medial parietal hub in SAD extends current frameworks for future research in anxiety disorders. PMID- 25124511 TI - The need of continuous focus on improved mentoring of trainees and young investigators in the field of andrology: highlights of current programs and opportunities for the future. PMID- 25124512 TI - Lessons learned in andrology: learning from experience - getting it wrong is alright. PMID- 25124510 TI - Mindfulness-based cognitive therapy versus psychoeducational intervention in bipolar outpatients with sub-threshold depressive symptoms: a randomized controlled trial. AB - BACKGROUND: The presence of depressive subsyndromal symptoms (SS) in bipolar disorder (BD) increases the risk of affective relapse and worsens social, cognitive functioning, and quality of life. Nonetheless, there are limited data on how to optimize the treatment of subthreshold depressive symptoms in BD. Mindfulness-Based Cognitive Therapy (MBCT) is a psychotherapeutic intervention that has been shown effective in unipolar depression. The assessment of its clinical effectiveness and its impact on biomarkers in bipolar disorder patients with subsyndromal depressive symptoms and psychopharmacological treatment is needed. METHODS/DESIGN: A randomized, multicenter, prospective, versus active comparator, evaluator-blinded clinical trial is proposed. Patients with BD and subclinical or mild depressive symptoms will be randomly allocated to: 1) MBCT added to psychopharmacological treatment; 2) a brief structured group psychoeducational intervention added to psychopharmacological treatment; 3) standard clinical management, including psychopharmacological treatment. Assessments will be conducted at screening, baseline, post-intervention (8 weeks) and 4 month follow-up post-intervention. The aim is to compare MBCT intervention versus a brief structured group psychoeducation. Our hypothesis is that MBCT will be more effective in reducing the subsyndromal depressive symptoms and will improve cognitive performance to a higher degree than the psychoeducational treatment. It is also hypothesized that a significant increase of BDNF levels will be found after the MBCT intervention. DISCUSSION: This is the first randomized controlled trial to evaluate the effects of MBCT compared to an active control group on depressive subthreshold depressive symptoms in patients with bipolar disorder. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02133170. Registered 04/30/2014. PMID- 25124513 TI - Validation of a laser-assisted wound measurement device in a wound healing model. AB - In the treatment and monitoring of a diabetic or chronic wound, accurate and repeatable measurement of the wound provides indispensable data for the patient's medical record. This study aims to measure the accuracy of the laser-assisted wound measurement (LAWM) device against traditional methods in the measurement of area, depth and volume. We measured four 'healing' wounds in a Play-Doh((r)) based model over five subsequent states of wound healing progression in which the model was irregularly filled in to replicate the healing process. We evaluated the LAWM device against traditional methods including digital photograph assessment with National Institutes of Health ImageJ software, measurements of depth with a ruler and weight-to-volume assessment with dental paste. Statistical analyses included analysis of variance (ANOVA) and paired t-tests. We demonstrate that there are significantly different and nearly statistically significant differences between traditional ruler depth measurement and LAWM device measurement, but there are no statistically significant differences in area measurement. Volume measurements were found to be significantly different in two of the wounds. Rate of percentage change was analysed for volume and depth in the wound healing model, and the LAWM device was not significantly different than the traditional measurement technique. While occasionally inaccurate in its absolute measurement, the LAWM device is a useful tool in the clinician's arsenal as it reliably measures rate of percentage change in depth and volume and offers a potentially aseptic alternative to traditional measurement techniques. PMID- 25124514 TI - Sub-chronically exposing mice to a polycyclic aromatic hydrocarbon increases lipid accumulation in their livers. AB - The potential for exposing humans and wildlife to environmental polycyclic aromatic hydrocarbons (PAHs) has increased. Risk assessments describing how PAHs disturb lipid metabolism and induce hepatotoxicity have only received limited attention. In the present study, seven-week-old male ICR mice received intraperitoneal injections of 0, 0.01, 0.1 or 1mg/kg body weight 3 methylcholanthrene (3MC) per week for 10 weeks. A high-fat diet was provided during the exposure. Histopathological lipid accumulation and lipid metabolism related genes were measured. We observed that sub-chronic 3MC exposure significantly increased lipid droplet and triacylglycerol (TG) levels in the livers. A low dose of 3MC activated the aryl hydrocarbon receptor, which negatively regulated lipid synthesis in the livers. The primary genes including acetyl-CoA carboxylase (Acc), fatty acid synthase (Fas) and stearoyl-CoA desaturase 1 (Scd1) decreased significantly when compared with those in the control group, indicating that de novo fatty acid synthesis in the hepatocytes was significantly inhibited by the sub-chronic 3MC exposure. However, the free fatty acid (FFA) synthesis in the adipose tissue was greatly enhanced by up regulating the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and sterol regulatory element binding protein-1c (SREBP1C) and target genes including Acc, Fas and Scd1. The synthesized FFA was released into the blood and then transported into the liver by the up-regulation of Fat and Fatp2, which resulted in the gradual accumulation of lipids in the liver. In conclusion, histological examinations and molecular level analyses highlighted the development of lipid accumulation and confirmed that 3MC significantly impaired lipid metabolism in mice. PMID- 25124515 TI - Investigation on the relationship between bioconcentration factor and distribution coefficient based on class-based compounds: The factors that affect bioconcentration. AB - Bioconcentration factor (BCF) is one of the most important parameters in the assessment of the potential hazard of new compounds in aquatic ecosystems. However, the factors that influence the estimation of BCFs for a large variety of chemicals have not been systemically investigated in the literature. In this paper, a large BCF data set containing 1088 nonionic and ionic organic compounds was used to study the relationship between BCF and molecular descriptors and influencing factors. Step-by-step analysis on the class-based compounds showed that nonlinear Gaussian and Sigmoid equations could well describe relationships between logBCF and distribution coefficient for the compounds over a wide range of structures and chloro or/and bromo substituted aromatics, respectively. The quality of fit from the nonlinear models is better than the BCFBAF method from the Epi Suite program for the class-based compounds. Systemic prediction deviations have been observed for some types of compounds. The reasons for systemic deviations for these compounds can be attributed to the difference in bioconcentration mechanism for hydrophilic compounds, transformation for hydroxyphenols and three-membered rings, physical barrier for long chain and large polycyclic compounds, difference in determining methods of BCF (kinetic and steady-state), bioavailability for highly hydrophobic compounds and accuracy of BCF measurements for compounds with extremely high or low BCFs. These factors are important and should be considered in any reliable bioconcentration prediction. PMID- 25124516 TI - Filariasis asymptomatically infected donors have lower levels of disialylated IgG compared to endemic normals. AB - Helminths induce strong regulatory and T helper 2-type responses, whereby antibody-derived host protection and regulation are essential components. Lymphatic filariasis is an immune-mediated spectral disease that manifests as two main clinical outcomes: chronic pathology or asymptomatic infection. These outcomes depend on a multitude of factors, including parasite-induced immunoregulation and host genetic background; antibody responses contribute to this outcome. N-glycosylation of the Fc region of antibodies is a post translational modification required for the structure and molecular function, influencing host inflammatory and regulatory responses. Altered IgG glycosylation correlates with disease, whereby decreased galactosylation is associated with inflammation while increased sialylation is associated with anti-inflammatory responses. We purified N-linked glycans from the Fc region of total IgG from Wuchereria bancrofti-infected patients characterizing the two clinical manifestations (chronic pathology and asymptomatic infection) and compared them to infection-free endemic normals. Using capillary electrophoresis, we found that there was no difference in galactosylation of total IgG between the three groups; however, asymptomatically infected patients had significantly lower levels of disialylated IgG compared to endemic normals and patients with pathology. These data suggest that while galactosylation does not contribute to disease outcome, sialylation may be involved in asymptomatic infection. PMID- 25124517 TI - Identification of differential selection traces in two Polish cattle breeds. AB - Genetic improvement of animals based on artificial selection is leading to changes in the frequency of genes related to desirable production traits. The changes are reflected by the neutral, intergenic single nucleotide polymorphims (SNPs) being in long-range linkage disequilibrium with functional polymorphisms. Genome-wide SNP analysis tools designed for cattle, allow for scanning divergences in allelic frequencies between distinct breeds and thus for identification of genomic regions which were divergently selected in breeds' histories. In this study, by using Bovine SNP50 assay, we attempted to identify genomic regions showing the highest differences in allele frequencies between two distinct cattle breeds - preserved, unselected Polish Red breed and highly selected Holstein cattle. Our study revealed 19 genomic regions encompassing 55 protein-coding genes and numerous quantitative trait loci which potentially may underlie some of the phenotypic traits distinguishing the breeds. PMID- 25124518 TI - Identification of a novel COL2A1 mutation (c.1744G>A) in a Japanese family: a case report. AB - INTRODUCTION: Mutations in the gene encoding the type II collagen gene (COL2A1) have been found to affect the entire skeletal system. Recently, inheritable skeletal dysplasia caused by novel COL2A1 mutations has been linked to an inherited disease of the hip joint that neither involves the entire skeletal system nor is characterized by the presence of concomitant disorders, such as spinal or ocular abnormalities. CASE PRESENTATION: A 27-year-old Japanese woman previously diagnosed with avasucular necrosis (AVN) of the femoral head on the basis of radiological findings was referred to the study site for surgical management of a painful hip joint. She had no history of disease but suffered from bilateral hip joint lesions. Analysis of her pedigree revealed that bilateral hip joint lesions affected more than three generations of her family. Based on these findings, haplotype analysis of her and her family members was performed by examining select candidate genes from the critical interval for epiphyseal dysplasia of the femoral head on 12q13 and sequencing the promoter and exonic regions of COL2A1. CONCLUSION: A novel COL2A1 mutation (c.1744G>A) was identified within one Japanese family. PMID- 25124519 TI - Neuroimmune biomarkers in schizophrenia. AB - Schizophrenia is a heterogeneous psychiatric disorder with a broad spectrum of clinical and biological manifestations. Due to the lack of objective tests, the accurate diagnosis and selection of effective treatments for schizophrenia remains challenging. Numerous technologies have been employed in search of schizophrenia biomarkers. These studies have suggested that neuroinflammatory processes may play a role in schizophrenia pathogenesis, at least in a subgroup of patients. The evidence indicates alterations in both pro- and anti inflammatory molecules in the central nervous system, which have also been found in peripheral tissues and may correlate with schizophrenia symptoms. In line with these findings, certain immunomodulatory interventions have shown beneficial effects on psychotic symptoms in schizophrenia patients, in particular those with distinct immune signatures. In this review, we evaluate these findings and their potential for more targeted drug interventions and the development of companion diagnostics. Although currently no validated markers exist for schizophrenia patient stratification or the prediction of treatment efficacy, we propose that utilisation of inflammatory markers for diagnostic and theranostic purposes may lead to novel therapeutic approaches and deliver more effective care for schizophrenia patients. PMID- 25124520 TI - Cortical thinning and caudate abnormalities in first episode psychosis and their association with clinical outcome. AB - First episode psychosis (FEP) has been associated with structural brain changes, largely identified by volumetric analyses. Advances in neuroimaging processing have made it possible to measure geometric properties that may identify subtle structural changes not appreciated by a measure of volume alone. In this study we adopt complementary methods of assessing the structural integrity of grey matter in FEP patients and assess whether these relate to patient clinical and functional outcome at 3 year follow-up. 1.5 Tesla T1-weighted Magnetic Resonance (MR) images were acquired for 46 patients experiencing their first episode of psychosis and 46 healthy controls. Cerebral cortical thickness and local gyrification index (LGI) were investigated using FreeSurfer software. Volume and shape of the hippocampus, caudate and lateral ventricles were assessed using manual tracing and spherical harmonics applied for shape description. A cluster of cortical thinning was identified in FEP compared to controls; this was located in the right superior temporal gyrus, sulcus, extended into the middle temporal gyrus (lateral temporal cortex - LTC). Bilateral caudate volumes were significantly lower in FEP relative to controls and the right caudate also displayed regions of shape deflation in the FEP group. No significant structural abnormalities were identified in cortical LGI or hippocampal or lateral ventricle volume/shape. Neither LTC nor caudate abnormalities were related to change in symptom severity or global functioning 3 years later. LTC and caudate abnormalities are present at the first episode of psychosis but do not appear to directly affect clinical or functional outcome. PMID- 25124522 TI - A simplified procedure for gram-scale production of sialylglycopeptide (SGP) from egg yolks and subsequent semi-synthesis of Man3GlcNAc oxazoline. AB - Heterogeneity of glycan structures in native glycoconjugates always hampers precise studies on carbohydrate-involved biological functions. To construct homogeneous glycoconjugates from natural resource of homogeneous glycans is therefore a practical approach to solve this problem. We report here an optimized procedure for gram-scale production of sialylglycopeptide (SGP) containing a disialyl biantennary complex-type N-glycan from egg yolks. Our new procedure simplified the extraction process by treating the egg yolk powder with 40% acetone, avoiding massive emulsification, high-speed centrifugation, and sophisticated chromatography in reported methods. Subsequent semi-synthesis of the N-glycan core Man3GlcNAc oxazoline from SGP was accomplished for the first time via glyco-trimming and successive oxazoline formation. This efficient semi synthesis provides an alternative to the pure chemical approach that involves multi-step total synthesis and facilitates the application of endo-glycosidase enabled chemoenzymatic synthesis of various homogeneous glycoconjugates. PMID- 25124521 TI - Replication of previous genome-wide association studies of psychiatric diseases in a large schizophrenia case-control sample from Spain. AB - Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM IV-TR diagnosis of SCZ and 2847 independent controls of European origin from Spain. A polygenic score analysis was also used to test the overall effect on the SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical significance (p=1.7*10(-4), Allelic odds ratio=1.21), a value very near to those reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC; rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency (risk or protection alleles) previously reported in the original GWAS (p<0.001). Our data strengthen the polygenic component of susceptibility to SCZ. Our findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common vulnerability in psychosis. PMID- 25124523 TI - Otolaryngology--head and neck surgery in undergraduate medical education: advances and innovations. AB - OBJECTIVES/HYPOTHESIS: Medical students graduate with the knowledge and skills to be undifferentiated general physicians. Otolaryngology-head and neck surgery (OtoHNS) is an essential component of primary healthcare, but is disproportionately under-represented in undergraduate medical education (UME). Advances and innovations in educational technology may represent an exciting and creative solution to this important problem. Failure to meet this educational need will result in substantial downstream effects in primary healthcare delivery. The objectives of this study were to 1) demonstrate current deficits in OtoHNS teaching at the UME level; 2) develop, validate, and critically appraise educational innovations that may enrich OtoHNS teaching in medical school curricula; and 3) propose a process for standardization of learning objectives for OtoHNS in UME as it relates to development and deployment of such educational tools. STUDY DESIGN: A white paper, prepared as a Triological Society thesis, which consolidates a prospective 10-year investigation of the problem of and potential solutions for under-representation of OtoHNS in UME. Cited datasets include multicenter surveys, cohort studies, and prospective, randomized controlled trials. METHODS: A series of published and unpublished data were synthesized that addresses the following: 1) the current state of OtoHNS teaching at the UME level with respect to content, volume, structure, and methods; and 2) educational innovations including e-learning and simulation with emphasis on validity and learning effectiveness. Educational innovations specific to postgraduate (residency) training were excluded. RESULTS: Data support the observation that there is uniformly disproportionate under-representation of OtoHNS within UME curricula. Medical school graduates, especially those pursuing primary care specialties, report poor overall comfort levels in managing OtoHNS problems. A series of novel teaching methods were developed and validated using e learning and simulation. Selected technologies may have a role in medical student teaching. It has been shown that e-learning has limited value in teaching complex spatial anatomy to novice learners, but good value in teaching basic clinical knowledge and selected technical skills. The role of simulation as it pertains to the novice learner is evolving. Important factors to consider during development of these tools include: 1) knowledge base and learning style of the learner, 2) complexity and nature of the learning objectives, 3) understanding the features and limitations of different technological genres, and 4) a team approach to module development. There remains a role for traditional teaching paradigms such as lectures, labs, and standardized patients; however, the choice of instructional genre should be fundamentally tailored to the nature of the learning outcomes. CONCLUSIONS: Enriching OtoHNS teaching in medical school is essential optimize primary care delivered to patients. Although e-learning and simulation are broadly accepted and desirable by today's medical students, these technologies should be woven into the fabric of UME pedagogical principles judiciously, and only after empiric assessment. Foundational to the development and implementation of these technologies is the framework of standardized competency-based learning objectives, common to all graduating medical students. LEVEL OF EVIDENCE: NA PMID- 25124524 TI - Effects of serial and concurrent training on acquisition and generalization. AB - Despite a large body of research demonstrating that generalization to novel stimuli can be produced by training sufficient exemplars, the methods by which exemplars can be trained remain unclear. The purpose of the current study was to evaluate 2 methods, serial and concurrent presentation of stimuli, to train sufficient exemplars. Five preschool children with developmental delays were taught to identify letters or letter sounds using serial and concurrent presentation. Generalization to untrained exemplars was evaluated for targets trained using each method. Participants reached the mastery criterion in fewer training sessions, on average, using the concurrent method of presentation than the serial method, and the concurrent method also resulted in greater generalization to untrained exemplars. PMID- 25124526 TI - Should we adjust for a confounder if empirical and theoretical criteria yield contradictory results? A simulation study. AB - Confounders can be identified by one of two main strategies: empirical or theoretical. Although confounder identification strategies that combine empirical and theoretical strategies have been proposed, the need for adjustment remains unclear if the empirical and theoretical criteria yield contradictory results due to random error. We simulated several scenarios to mimic either the presence or the absence of a confounding effect and tested the accuracy of the exposure outcome association estimates with and without adjustment. Various criteria (significance criterion, Change-in-estimate(CIE) criterion with a 10% cutoff and with a simulated cutoff) were imposed, and a range of sample sizes were trialed. In the presence of a true confounding effect, unbiased estimates were obtained only by using the CIE criterion with a simulated cutoff. In the absence of a confounding effect, all criteria performed well regardless of adjustment. When the confounding factor was affected by both exposure and outcome, all criteria yielded accurate estimates without adjustment, but the adjusted estimates were biased. To conclude, theoretical confounders should be adjusted for regardless of the empirical evidence found. The adjustment for factors that do not have a confounding effect minimally effects. Potential confounders affected by both exposure and outcome should not be adjusted for. PMID- 25124527 TI - Pentacoordinate phosphorus in a high-pressure polymorph of phosphorus nitride imide P4N6(NH). AB - Coordination numbers higher than usual are often associated with superior mechanical properties. In this contribution we report on the synthesis of the high-pressure polymorph of highly condensed phosphorus nitride imide P4 N6 (NH) representing a new framework topology. This is the first example of phosphorus in trigonal-bipyramidal coordination being observed in an inorganic network structure. We were able to obtain single crystals and bulk samples of the compound employing the multi-anvil technique. gamma-P4 N6 (NH) has been thoroughly characterized using X-ray diffraction, solid-state NMR and FTIR spectroscopy. The synthesis of gamma-P4 N6 (NH) gives new insights into the coordination chemistry of phosphorus at high pressures. The synthesis of further high-pressure phases with higher coordination numbers exhibiting intriguing physical properties seems within reach. PMID- 25124525 TI - Maternal periconceptional occupational pesticide exposure and neural tube defects. AB - BACKGROUND: Adverse associations between maternal pesticide exposure and neural tube defects (NTDs) have been suggested but not consistently observed. This study used data from the multisite National Birth Defects Prevention Study to examine associations between maternal periconceptional (1 month preconception through 2 months postconception) occupational pesticide exposure and NTDs. METHODS: Mothers of 502 NTD cases and 2950 unaffected live-born control infants with estimated delivery dates from 1997 through 2002 were included. Duration, categorical intensity scores, and categorical frequency scores for pesticide classes (e.g., insecticides) were assigned using a modified, literature-based job-exposure matrix and maternal-reported occupational histories. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated based on fitted multivariable logistic regression models that described associations between maternal periconceptional occupational pesticide exposure and NTDs. The aORs were estimated for pesticide exposure (any [yes/no] and cumulative exposure [intensity * frequency * duration] to any pesticide class, each pesticide class, or combination of pesticide classes) and all NTD cases combined and NTD subtypes. RESULTS: Positive, but marginally significant or nonsignificant, aORs were observed for exposure to insecticides + herbicides for all NTD cases combined and for spina bifida alone. Similarly, positive aORs were observed for any exposure and cumulative exposure to insecticides + herbicides + fungicides and anencephaly alone and encephalocele alone. All other aORs were near unity. CONCLUSION: Pesticide exposure associations varied by NTD subtype and pesticide class. Several aORs were increased, but not significantly. Future work should continue to examine associations between pesticide classes and NTD subtypes using a detailed occupational pesticide exposure assessment and examine pesticide exposures outside the workplace. PMID- 25124528 TI - Cost-effectiveness of using small vertebrates as indicators of disturbance. AB - In species-rich tropical forests, effective biodiversity management demands measures of progress, yet budgetary limitations typically constrain capacity of decision makers to assess response of biological communities to habitat change. One approach is to identify ecological-disturbance indicator species (EDIS) whose monitoring is also monetarily cost-effective. These species can be identified by determining individual species' responses to disturbance across a gradient; however, such responses may be confounded by factors other than disturbance. For example, in mountain environments the effects of anthropogenic habitat alteration are commonly confounded by elevation. EDIS have been identified with the indicator value (IndVal) metric, but there are weaknesses in the application of this approach in complex montane systems. We surveyed birds, small mammals, bats, and leaf-litter lizards in differentially disturbed cloud forest of the Ecuadorian Andes. We then incorporated elevation in generalized linear (mixed) models (GL(M)M) to screen for EDIS in the data set. Finally, we used rarefaction of species accumulation data to compare relative monetary costs of identifying and monitoring EDIS at equal sampling effort, based on species richness. Our GL(M)M generated greater numbers of EDIS but fewer characteristic species relative to IndVal. In absolute terms birds were the most cost-effective of the 4 taxa surveyed. We found one low-cost bird EDIS. In terms of the number of indicators generated as a proportion of species richness, EDIS of small mammals were the most cost-effective. Our approach has the potential to be a useful tool for facilitating more sustainable management of Andean forest systems. PMID- 25124529 TI - Comparison of sub-bandage pressures achieved by 3 abdominal bandaging techniques in horses. AB - REASONS FOR PERFORMING STUDY: Clinicians frequently place post operative abdominal bandages on horses undergoing laparotomies. Presently, no information exists on the amount of incisional support provided by these bandages. Determination of sub-bandage pressure provides a means of comparing the ability of different bandages to support incisions. OBJECTIVES: Determination of sub bandage pressure over a 24 h period using 3 bandaging techniques. STUDY DESIGN: A randomised, crossover design using 9 healthy horses. METHODS: Horses were randomly assigned to a treatment regimen consisting of placement of 3 abdominal bandage types, namely an elastic bandage (ELA), the CM(TM) Hernia Heal Belt (CM) or a nylon binder (NYL). The sub-bandage pressures for each bandage were measured with the Picopress(r) compression-measuring system at 0, 2, 4, 6, 8, 12, 16, 20 and 24 h after application. RESULTS: No time and treatment interactions were observed, and bandage pressures were maintained within each treatment group over the 24 h period. Mean sub-bandage pressures were different between all treatment groups (P < 0.001) at 39 (95% confidence interval, 36.7-40.5 mmHg), 25 (95% confidence interval, 23.9-27.7 mmHg) and 5 mmHg (95% confidence interval, 4.1-7.8 mmHg) for CM, ELA and NYL bandages, respectively. Horses were more likely to lie down with the CM (P = 0.02) and ELA treatments (P = 0.0002) when compared with the NYL treatment. The ELA bandages were more likely to displace caudally compared with both CM and NYL bandages. CONCLUSIONS: The CM bandage was superior to both ELA and NYL bandages with regard to measured sub-bandage pressure over the 24 h period. The clinical significance of the differences in sub-bandage pressure between treatments cannot be determined by this study. PMID- 25124530 TI - Hedonic tone is associated with left supero-lateral medial forebrain bundle microstructure. AB - BACKGROUND: The medial forebrain bundle (MFB) is an important pathway of the reward system. Two branches have been described using diffusion magnetic resonance imaging (MRI)-based tractography: the infero-medial MFB (imMFB) and the supero-lateral MFB (slMFB). Previous studies point to white-matter microstructural alterations of the slMFB in major depressive disorder (MDD) during acute episodes. To extend this finding, this study investigates whether white-matter microstructure is also altered in MDD patients that are in remission. Further, we explore associations between diffusion MRI-based metrics of white-matter microstructure of imMFB, slMFB and hedonic tone, the ability to derive pleasure. METHOD: Eighteen remitted depressed (RD) and 22 never depressed (ND) participants underwent high angular resolution diffusion-weighted imaging (HARDI) scans. To reconstruct the two pathways of the MFB (imMFB and slMFB) we used the damped Richardson-Lucy (dRL) algorithm. Mean fractional anisotropy (FA) was sampled along the tracts. RESULTS: Mean FA of imMFB, slMFB and a comparison tract (the middle cerebellar peduncle) did not differ between ND and RD participants. Hedonic capacity correlated negatively with mean FA of the left slMFB, explaining 21% of the variance. CONCLUSIONS: Diffusion MRI-based metrics of white-matter microstructure of the MFB in RD do not differ from ND. Hedonic capacity is associated with altered white-matter microstructure of the slMFB. PMID- 25124531 TI - Microstructural trabecular bone from patients with osteoporotic hip fracture or osteoarthritis: its relationship with bone mineral density and bone remodelling markers. AB - Osteoporosis (OP) and osteoarthritis (OA) are the most prevalent musculoskeletal disorders in the elderly but the relationship between them is unclear. The purposes of this study are to analyze the bone turnover markers (BTM), bone mineral density (BMD) and the structural and mechanical properties of trabecular bone in patients with OP and OA, and to explore the relationship between these two diseases. We studied 12 OP patients and 13 OA patients. We analyzed BTM (beta CrossLaps and PINP), BMD and microstructural and biomechanical parameters (micro CT). Our results were: OP group has higher levels of beta-CrossLaps and lower BMD at the femoral neck. Also, OP patients have a decreased volume of trabecular bone and less trabecular number, with architecture showing prevalence of rod-like trabeculae and worse connectivity than OA patients. The biomechanical parameters were worse in OP patients. BMD was correlated with almost all the structural and biomechanical parameters. Moreover, beta-CrossLaps was negatively correlated with hip BMD and with bone surface density and positively with trabecular separation. BTM, BMD and bone microstructural changes in osteoporosis are opposite to those of OA. These findings justify a less resistant bone with higher risk of fragility fractures in OP patients. These histomorphometric and biomechanical changes may be suspected by measuring of BMD and beta-CrossLaps levels. PMID- 25124532 TI - Use of FRAX(r)-based fracture risk assessments to identify patients who will benefit from osteoporosis therapy. AB - Several pharmacological interventions, including selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab, and strontium ranelate have demonstrated efficacy in reducing the incidence of osteoporotic fractures, the most severe consequence of postmenopausal osteoporosis. Until recently, bone mineral density (BMD) was the primary factor used to determine which postmenopausal women may require osteoporosis treatment. However, clinical guidelines now recommend the use of the Fracture Risk Assessment Tool (FRAX((r))), a computer-based algorithm introduced by the World Health Organization, to help primary care physicians identify postmenopausal women who may be candidates for pharmacological osteoporosis therapy based on the level of fracture risk. Beyond its utility as a resource for determining whether or not to initiate osteoporosis treatment, clinical studies have begun to evaluate the correlation between FRAX((r))-based 10-year fracture probability and efficacy of different osteoporosis treatments. Bazedoxifene, clodronate, and denosumab have shown greater fracture risk reduction at higher FRAX((r))-based 10-year fracture probabilities, but the efficacy of raloxifene, alendronate, and strontium ranelate were relatively stable regardless of fracture probability. In summary, these data suggest that the relationship between FRAX((r))-based fracture probability and efficacy of different osteoporosis treatments varies depending upon the agent in question. PMID- 25124533 TI - Mass spectrometry based quantitative proteomics and integrative network analysis accentuates modulating roles of annexin-1 in mammary tumorigenesis. AB - Annexin-1 (ANXA1) is known to be involved in important cellular processes and implicated in cancer. Our previous study showed its roles in cell migration and DNA-damage response processes in breast cancer initiation. In order to understand its roles in tumorigenesis, we extended our studies to analyze tumors derived from polyomavirus middle T-antigen ANXA1 heterozygous (ANXA1(+/-) ) and ANXA1 null (ANXA1(-/-) ) mice. We performed quantitative comparison of ANXA1(+/-) and ANXA1(-/-) tumors employing reductive dimethyl labeling quantitative proteomics. We observed 253 differentially expressed proteins (DEPs) with high statistical significance among over 5000 quantified proteins. Combinatorial use of pathway and network-based computational analyses of the DEPs revealed that ANXA1 primarily modulates processes related to cytoskeletal remodeling and immune responses in these mammary tumors. Of particular note, ANXA1(-/-) tumor showed reduced expression of a known epithelial-to-mesenchymal transition (EMT) marker vimentin, as well as myosin light-chain kinase, which has been reported to induce Rho-kinase mediated assembly of stress fibers known to be implicated in EMT. Integrative network analysis of established interactome of ANXA1 alongside with DEPs further highlights the involvement of ANXA1 in EMT. Functional role of ANXA1 in tumorigenesis was established in invasion assay where knocking down ANXA1 in murine mammary tumor cell line 168FARN showed lower invasive capability. Altogether, this study emphasizes that ANXA1 plays modulating roles contributing to invasion-metastasis in mammary tumorigenesis, distinctive to its roles in cancer initiation. PMID- 25124534 TI - Self-excising integrative yeast plasmid vectors containing an intronated recombinase gene. AB - Site-specific recombinases are widely used for selectable marker recycling in molecular-genetic manipulations with eukaryotic cells. This usually involves the use of two genetic constructs, one of which possesses a selectable marker flanked by the recombinase recognition sequences, while the other one bears the recombinase gene. Combining the recombinase gene with its recognition sequences in one plasmid is usually avoided, as it may lead to undesirable recombination due to promoter leakage, while the plasmid is maintained in Escherichia coli cells. Here, we describe yeast vectors possessing Cre recombinase genes under control of regulatable yeast promoters and loxP sequences for the in vivo vector backbone excision. The plasmid stability in E. coli is ensured by the presence of an intron in the recombinase gene. Applicability of these vectors was validated by disruptions of the Hansenula polymorpha PMC1 and Saccharomyces cerevisiae HSP104 and PRB1 genes. PMID- 25124536 TI - Hooked on UVR. PMID- 25124535 TI - Impact of high-sensitivity Troponin T on hospital admission, resources utilization, and outcomes. AB - AIMS: The use of high-sensitivity cardiac Troponin T (hs-cTnT) assay might lead to overdiagnosis and overtreatment of Acute Coronary Syndromes (ACS). This study assessed the epidemiological, clinical and prognostic impact of introducing hs cTnT in the everyday clinical practice of an Emergency Department. METHODS AND RESULTS: We compared all consecutive patients presenting with suspected ACS at the Emergency Department, for whom troponin levels were measured. In particular, we considered 597 patients presenting during March 2010, when standard cardiac Troponin T (cTnT) assay was used, and 629 patients presenting during March 2011, when hs-cTnT test was used. Patients with suspected ACS and troponin levels above the 99th percentile (Upper Reference Limit, URL) significantly increased when using an hs-cTnT assay (17.2% vs. 37.4%, p< 0.001). Accordingly, also the mean GRACE risk score increased (124.2 +/- 37.2 vs. 136.7 +/- 32.2; p< 0.001). However, the final diagnosis of Acute Myocardial Infarction (AMI) did not change significantly (8.7% vs. 6.8%, p=0.263) by using a rising and/or falling pattern of hs-cTnT (change >= 50% or >= 20% depending on baseline values). In addition, no significant differences were found between the two study groups with respect to in-hospital (2.7% vs. 1.9%, p=0.366) and 1-year mortality (9.8% vs. 7.6%, p=0.216). CONCLUSIONS: We did not observe overdiagnosis and overtreatment issues in presenters with suspected ACS managed by appropriate changes in hs-cTnT levels, despite the increase in the number of patients presenting with abnormal troponin levels. This occurred without a rise in short-term and mid-term mortality. PMID- 25124542 TI - Antibody response to dengue virus. AB - In this review, we discuss the current knowledge of the role of the antibody response against dengue virus and highlight novel insights into targets recognized by the human antibody response. We also discuss how the balance of pathological and protective antibody responses in the host critically influences clinical aspects of the disease. PMID- 25124540 TI - IFN-gamma and TNF associated with severe falciparum malaria infection in Saudi pregnant women. AB - BACKGROUND: Tumour necrosis factor (TNF) and interferon gamma (IFN-gamma), encoded by TNF-836 C/A (rs 1800630) and IFN-gamma -1616 C/T (rs2069705) genes, are key immunological mediators that are believed to both play protective and pathological roles in malaria. The aim of this study was to investigate the relationship between TNF-836 C/A and IFN-gamma-1616 C/T polymorphism and susceptibility to severe malaria in pregnant women. METHODS: A prospective cohort (cross-sectional) study was conducted in pregnant women attending the out-patient clinic in King Fahad Specialist Hospital in Jazan (KFSHJ), with a clinical diagnosis of malaria. A total of one hundred and eighty six pregnant women were genotyped for single nucleotide polymorphism (SNP) for TNF and IFN-gamma using Taqman(r) MGB Probes. Serum cytokine concentrations were measured by sandwich ELISA method. RESULTS: A hospital case-control study of severe malaria in a Saudi population identified strong associations with individual single-nucleotide polymorphisms in the TNF and IFN-gamma genes, and defined TNF-836 C and IFN-gamma 1616 T genotypes and alleles which were statistically significantly associated with severe malaria infection. Furthermore, TNF-836 CC and IFN-gamma-1616 TT genotypes were associated with higher serum concentration of TNF and IFN-gamma, respectively, and with susceptibility to severe malaria. CONCLUSIONS: This data provides a starting point for functional and genetic analysis of the TNF and IFN gamma genomic region in malaria infection affecting Saudi populations. PMID- 25124541 TI - Efficacy and safety of canagliflozin in subjects with type 2 diabetes: systematic review and meta-analysis. AB - PURPOSE: To assess the efficacy and safety of the novel sodium glucose co transporter 2 (SGLT2) inhibitor-canagliflozin for type 2 diabetes (T2DM). METHODS: A search of Medline (1946-January 2014), Embase (1950-January 2014), and The Cochrane Library for randomized controlled trials of canagliflozin compared to placebo or active comparator in T2DM was performed. Clinical Trials website and unpublished U.S. Food and Drug Administration data were also searched. RESULTS: Ten trials including 6,701 patients were analyzed. Compared with placebo, canagliflozin produced absolute reductions in glycated hemoglobin A1c levels when used as monotherapy (weighted mean difference (WMD) -1.08%, 95% confidence interval (CI) [-1.25 to -0.90], p < 0.00001) or add-on treatment (WMD 0.73%, 95%CI [-0.84 to -0.61], p < 0.00001). When compared with other active comparators, canagliflozin significantly reduced HbA1c by -0.21% (WMD, 95%CI [ 0.33 to -0.08], p = 0.001). Canagliflozin led to greater body weight loss (vs. placebo, WMD -2.81 kg, 95%CI [-3.26 to -2.37]; vs. active comparators, WMD -3.49 kg, 95%CI [-4.86 to -2.12]). Hypoglycemia with canagliflozin was similar to placebo or sitagliptin, and was lower than glimepiride (risk ratio (RR) 0.15, 95%CI [0.10 to 0.22]). Genital tract infections were more common with canagliflozin (vs. placebo, RR 3.76, 95%CI [2.23 to 6.35]; vs. active comparators, RR 4.95, 95%CI [3.25 to 7.52]). Similar incidences of urinary tract infections were noted with canagliflozin compared with control groups. CONCLUSION: Canagliflozin led to improvements in reducing glycated hemoglobin A1c levels and body weight with low risk of hypoglycemia in patients with T2DM. Common adverse effects including genital tract infections and osmotic diuresis related AEs were identified and reviewed. Risks of cardiovascular events are even less certain, and more data on long-term effects are needed. PMID- 25124543 TI - Flatland goes 3D. PMID- 25124545 TI - Manifold learning based ECG-free free-breathing cardiac CINE MRI. AB - PURPOSE: To present and validate a manifold learning (ML)-based method that can estimate both cardiac and respiratory navigator signals from electrocardiogram (ECG)-free free-breathing cardiac magnetic resonance imaging (MRI) data to achieve self-gated retrospective CINE reconstruction. MATERIALS AND METHODS: In this work the use of the ML method is demonstrated for 2D cardiac CINE to achieve both cardiac and respiratory self-gating without the need of an external navigator or ECG signal. This is achieved by sequentially applying ML to two sets of retrospectively reconstructed real-time images with differing temporal resolutions. A 1D cardiac signal is estimated by applying ML to high temporal resolution real-time images reconstructed from the acquired data. Using the estimated cardiac signal, a 1D respiratory signal was obtained by applying the ML method to low temporal resolution images reconstructed from the same acquired data for each cardiac cycle. Data were acquired in five volunteers with a 2D golden angle radial trajectory in a balanced steady-state free precession (b SSFP) acquisition. The accuracy of the estimated cardiac signal was calculated as the standard deviation of the temporal difference between the estimated signal and the recorded ECG. The correlation between the estimated respiratory signal and standard pencil beam navigator signal was evaluated. Gated CINE reconstructions (20 cardiac phases per cycle, temporal resolution ~30 msec) using the estimated cardiac and respiratory signals were qualitatively compared against conventional ECG-gated breath-hold CINE acquisitions. RESULTS: Accurate cardiac signals were estimated with the proposed method, with an error standard deviation in comparison to ECG lower than 20 msec. Respiratory signals estimated with the proposed method achieved a mean cross-correlation of 94% with respect to standard pencil beam navigator signals. Good quality visual scores of 2.80 +/- 0.45 (scores from 0, bad, to 4, excellent quality) were observed for the proposed approach in comparison with the conventional ECG-gated breath-hold images (visual score: 3.00 +/- 0.71). CONCLUSION: Accurate respiratory and cardiac navigator signals can be estimated using the proposed framework from the acquired data itself, resulting in retrospective self-gated CINE reconstruction with high spatial and temporal quality. PMID- 25124544 TI - Prophylactic effect of human lactoferrin against Streptococcus mutans bacteremia in lactoferrin knockout mice. AB - Streptococcus mutans is the primary agent of dental caries, which is often detected in transient bacteremia. Lactoferrin is a multifunctional glycoprotein showing antibacterial activities against several Streptococcus species. We reported here the prophylactic effect of human lactoferrin (hLF) in a lactoferrin knockout mouse (LFKO-/-) bacteremic model. The hLF treatment significantly cleared S. mutans from the blood and organs of bacteremic mice when compared to the non-hLF treated mice. Further, analysis of serum cytokines, spleen and liver cytokine mRNA levels revealed that hLF prophylaxis modulates their release differently when compared to the non-hLF treated group. C-reactive protein level (P = 0.003) also decreased following hLF prophylaxis in S. mutans induced bacteremic mice. Additional quantitative RT-PCR analysis revealed that hLF prophylaxis significantly decreased the expression level of IFN-gamma, TNF-alpha, IL-1beta, IL-6, MPO and iNOS in spleen and liver. These results suggested that the hLF protects the host against S. mutans-induced experimental bacteremia. PMID- 25124546 TI - Segmental uniparental isodisomy of chromosome 6 causing transient diabetes mellitus and merosin-deficient congenital muscular dystrophy. AB - Segmental uniparental isodisomy (iUPD) is a rare genetic event that may cause aberrant expression of imprinted genes, and reduction to homozygosity of a recessive mutation. Transient neonatal diabetes mellitus (TNDM) is typically caused by imprinting aberrations in chromosome 6q24 TNDM differentially methylated region (DMR). Approximately, 15.12 Mb upstream in 6q22-q23 is located LAMA2, the gene responsible of merosin-deficient congenital muscular dystrophy type 1A (MDC1A). We investigated a patient diagnosed both with TNDM and MDC1A, born from a twin dichorionic discordant pregnancy. Parents are first-degree cousins. Methylation sensitive-PCR of the imprinted 6q24 TNDM CpG island showed only the non-methylated (paternal) allele. Microsatellite markers and SNP array profiling disclosed normal biparental inheritance at 6p and a segmental paternal iUPD, between 6q22.33 and 6q27. Sequencing of LAMA2 exons showed a homozygous frameshift mutation, c.7490_7493dupAAGA, which predicts p.Asp2498GlufsX4, in exon 54. Her father, but not her mother, was a carrier of the mutation. While segmental paternal iUPD6 causing TNDM was reported twice, there are no previous reports of MDC1A caused by this event. This is a child with two genetic disorders, yet neither is caused by the parental consanguinity, which reinforces the importance of considering different etiological mechanisms in the genetic clinic. PMID- 25124547 TI - Retrospective data analysis and proposal of a practical acceptance criterion for inter-laboratory cross-validation of bioanalytical methods using liquid chromatography/tandem mass spectrometry. AB - The purpose of this study is to conduct a retrospective data analysis for inter laboratory cross-validation studies to set a reasonable and practical acceptance criterion based on a number of cross-validation results. From the results of cross-validation studies for 16 compounds and their metabolites, analytical bias and variation were evaluated. The accuracy of cross-validation samples was compared with that of quality control (QC) samples with statistical comparison of the analytical variation. An acceptance criterion was derived with a confidential interval approach. As the results, while a larger bias was observed for the cross validation samples, the bias was not fully caused by analytical variation or bias attributable to the analytical methods. The direction of the deviation between the cross-validation samples and QC samples was random and not concentration dependent, suggesting that inter-laboratory variability such as preparation errors could be a source of bias. A derived acceptance criterion corresponds to one prescribed in the Guideline on bioanalytical method validation from the Ministry of Health, Labour and Welfare in Japan and is a little wider than one in the European Medical Agency. In conclusion, thorough retrospective data analysis revealed potential causes of larger analytical bias in inter-laboratory cross validation studies. A derived acceptance criterion would be practical and reasonable for the inter-laboratory cross-validation study. PMID- 25124548 TI - Behavioral extremes of trait anxiety in mice are characterized by distinct metabolic profiles. AB - No comprehensive metabolic profile of trait anxiety is to date available. To identify metabolic biosignatures for different anxiety states, we compared mice selectively inbred for ~ 40 generations for high (HAB), normal (NAB) or low (LAB) anxiety-related behavior. Using a mass spectrometry-based targeted metabolomics approach, we quantified the levels of 257 unique metabolites in the cingulate cortex and plasma of HAB, NAB and LAB mice. We then pinpointed affected molecular systems in anxiety-related behavior by an in silico pathway and network prediction analysis followed by validation of in silico predicted alterations with molecular assays. We found distinct metabolic profiles for different trait anxiety states and detected metabolites with altered levels both in cingulate cortex and plasma. Metabolomics data revealed common candidate biomarkers in cingulate cortex and plasma for anxiety traits and in silico pathway analysis implicated amino acid metabolism, pyruvate metabolism, oxidative stress and apoptosis in the regulation of anxiety-related behavior. We report characteristic biosignatures for trait anxiety states and provide a network map of pathways involved in anxiety-related behavior. Pharmacological targeting of these pathways will enable a mechanism-based approach for identifying novel therapeutic targets for anxiety disorders. PMID- 25124549 TI - Suicide in children and young adolescents: a 25-year database on suicides from Northern Finland. AB - Despite the large amount of research on adolescent suicidality, there are few detailed studies illustrating the characteristics of child and adolescent completed suicide. Our study presents the characteristics of child and adolescent suicides occurring over a period of 25 years within a large geographical area in Northern Finland, with a special focus on gender differences. The study sample included all 58 suicides among children and adolescents (<18 years) occurring in the province of Oulu in Finland between 1988 and 2012. The data is based on documents pertaining to establish the cause of death from forensic autopsy investigations. A register linkage to the data from the Finnish Hospital Discharge Register (FHDR) was also made. 79% of the suicide victims were male. Violent suicide methods predominated in both genders (males 98%, females 83%). While symptoms of mental illness were common, only a minority (15% of males and 17% of females) had a previous history of psychiatric hospitalization. 17% of females but none of the males had been hospitalized previously due to self poisoning. A greater proportion of females than males had a history of self cutting (33% vs. 7%) and previous suicide attempts (25% vs. 4%). 48% of males and 58% of females were under the influence of alcohol at the time of their suicide, and alcohol intoxication was related to suicides during the night. One fifth of the adolescents screened positive for substances other than alcohol. The results of this study indicate that there are similarities but also some differences in the characteristics of male and female suicides in adolescents. PMID- 25124550 TI - Zolpidem and the risk of Parkinson's disease: a nationwide population-based study. AB - BACKGROUND: This nationwide population-based study investigated the risk of Parkinson's disease (PD) after zolpidem use in patients with sleep disturbance using the National Health Insurance Research Database (NHIRD) in Taiwan. MATERIAL AND METHODS: In total, 59,548 adult patients newly diagnosed with sleep disturbance and who used zolpidem were recruited as the study cohort, along with 42,171 subjects who did not use zolpidem as a comparison cohort from 2002 to 2009. Each patient was monitored for 5 years, and those who subsequently had PD were identified. A Cox proportional hazards model was used to compare the risk of PD between the study and comparison cohorts after adjusting for possible confounding risk factors. RESULTS: The patients who received zolpidem had a higher cumulative rate of PD than those who did not receive zolpidem during the 5 year follow-up period (1.2% vs. 0.5%, P < 0.001). The adjusted hazard ratios were 1.10 (95% CI, 0.88-1.37), 1.41 (95% CI, 1.17-1.72), and 1.27 (95% CI, 1.05-1.55) for zolpidem use with 28-90, 91-365, and more than 365 cumulative defined daily doses (cDDDs), respectively, compared to those who did not use zolpidem. CONCLUSIONS: Among the patients with sleep disturbance, zolpidem use increased the risk of PD after 5 years of follow-up. Further mechanistic research of zolpidem effect in PD is needed. PMID- 25124551 TI - Real-time in vivo periprostatic nerve tracking using multiphoton microscopy in a rat survival surgery model: a promising pre-clinical study for enhanced nerve sparing surgery. AB - OBJECTIVES: To assess the ability of multiphoton microscopy (MPM) to visualise, differentiate and track periprostatic nerves in an in vivo rat model, mimicking real-time imaging in humans during RP and to investigate the tissue toxicity and reproducibility of in vivo MPM on prostatic glands in the rat after imaging and final histological correlation study. MATERIALS AND METHODS: In vivo prostatic rat imaging was carried out using a custom-built bench-top MPM system generating real-time three-dimensional histological images, after performing survival surgery consisting of mini-laparotomies under xylazine/ketamine anaesthesia exteriorising the right prostatic lobe. The acquisition time and the depth of anaesthesia were adjusted for collecting multiple images in order to track the periprostatic nerves in real-time. The rats were then monitored for 15 days before undergoing a new set of imaging under similar settings. After humanely killing the rats, their prostates were submitted for routine histology and correlation studies. RESULTS: In vivo MPM images distinguished periprostatic nerves within the capsule and the prostatic glands from fresh unprocessed prostatic tissue without the use of exogenous contrast agents or biopsy sample. Real-time nerve tracking outlining the prostate was feasible and acquisition was not disturbed by motion artefacts. No serious adverse event was reported during rat monitoring; no tissue damage due to laser was seen on the imaged lobe compared with the contralateral lobe (control) allowing comparison of their corresponding histology. CONCLUSIONS: For the first time, we have shown that in vivo tracking of periprostatic nerves using MPM is feasible in a rat model. Development of a multiphoton endoscope for intraoperative use in humans is currently in progress and must be assessed. PMID- 25124552 TI - Comparative genomics highlights the unique biology of Methanomassiliicoccales, a Thermoplasmatales-related seventh order of methanogenic archaea that encodes pyrrolysine. AB - BACKGROUND: A seventh order of methanogens, the Methanomassiliicoccales, has been identified in diverse anaerobic environments including the gastrointestinal tracts (GIT) of humans and other animals and may contribute significantly to methane emission and global warming. Methanomassiliicoccales are phylogenetically distant from all other orders of methanogens and belong to a large evolutionary branch composed by lineages of non-methanogenic archaea such as Thermoplasmatales, the Deep Hydrothermal Vent Euryarchaeota-2 (DHVE-2, Aciduliprofundum boonei) and the Marine Group-II (MG-II). To better understand this new order and its relationship to other archaea, we manually curated and extensively compared the genome sequences of three Methanomassiliicoccales representatives derived from human GIT microbiota, "Candidatus Methanomethylophilus alvus", "Candidatus Methanomassiliicoccus intestinalis" and Methanomassiliicoccus luminyensis. RESULTS: Comparative analyses revealed atypical features, such as the scattering of the ribosomal RNA genes in the genome and the absence of eukaryotic-like histone gene otherwise present in most of Euryarchaeota genomes. Previously identified in Thermoplasmatales genomes, these features are presently extended to several completely sequenced genomes of this large evolutionary branch, including MG-II and DHVE2. The three Methanomassiliicoccales genomes share a unique composition of genes involved in energy conservation suggesting an original combination of two main energy conservation processes previously described in other methanogens. They also display substantial differences with each other, such as their codon usage, the nature and origin of their CRISPRs systems and the genes possibly involved in particular environmental adaptations. The genome of M. luminyensis encodes several features to thrive in soil and sediment conditions suggesting its larger environmental distribution than GIT. Conversely, "Ca. M. alvus" and "Ca. M. intestinalis" do not present these features and could be more restricted and specialized on GIT. Prediction of the amber codon usage, either as a termination signal of translation or coding for pyrrolysine revealed contrasted patterns among the three genomes and suggests a different handling of the Pyl-encoding capacity. CONCLUSIONS: This study represents the first insights into the genomic organization and metabolic traits of the seventh order of methanogens. It suggests contrasted evolutionary history among the three analyzed Methanomassiliicoccales representatives and provides information on conserved characteristics among the overall methanogens and among Thermoplasmata. PMID- 25124553 TI - Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins. AB - During the effector CD8+ T-cell response, transcriptional differentiation programs are engaged that promote effector T cells with varying memory potential. Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, it is unclear if the lack of cell death enhances memory. Here, we investigated effector CD8+ T cell fate in mice whose death program has been largely disabled because of the loss of Bim. Interestingly, the absence of Bim resulted in a significant enhancement of effector CD8+ T cells with more memory potential. Bim-driven control of memory T-cell development required T-cell-specific, but not dendritic cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim promoted skewing toward memory precursors, by enhancing the survival of memory precursors, and limiting the availability of IL-15. Decreased IL-15 availability in Bim-deficient mice facilitated the elimination of cells with less memory potential via the additional pro-apoptotic molecules Noxa and Puma. Combined, these data show that Bim controls memory development by limiting the survival of pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim limits the role of Noxa and Puma in causing the death of effector cells with less memory potential. PMID- 25124554 TI - Liver X receptor beta activation induces pyroptosis of human and murine colon cancer cells. AB - Liver X receptors (LXRs) have been proposed to have some anticancer properties, through molecular mechanisms that remain elusive. Here we report for the first time that LXR ligands induce caspase-1-dependent cell death of colon cancer cells. Caspase-1 activation requires Nod-like-receptor pyrin domain containing 3 (NLRP3) inflammasome and ATP-mediated P2 * 7 receptor activation. Surprisingly, LXRbeta is mainly located in the cytoplasm and has a non-genomic role by interacting with pannexin 1 leading to ATP secretion. Finally, LXR ligands have an antitumoral effect in a mouse colon cancer model, dependent on the presence of LXRbeta, pannexin 1, NLRP3 and caspase-1 within the tumor cells. Our results demonstrate that LXRbeta, through pannexin 1 interaction, can specifically induce caspase-1-dependent colon cancer cell death by pyroptosis. PMID- 25124557 TI - A smart "sense-act-treat" system: combining a ratiometric pH sensor with a near infrared therapeutic gold nanocage. AB - Herein, we design a "sense-act-treat" system via the combination of a ratiometric pH sensor with a therapeutic gold nanocage. Our design could "sense" the tumor through two-state switching of fluorescence and further provide chemotherapy and hyperthermia for "treating" the tumor, showing the potential for future biomedical applications. PMID- 25124556 TI - GRP78 clustering at the cell surface of neurons transduces the action of exogenous alpha-synuclein. AB - Mutation or multiplication of the alpha-synuclein (Syn)-encoding gene is frequent cause of early onset Parkinson's disease (PD). Recent evidences point to the pathogenic role of excess Syn also in sporadic PD. Syn is a cytosolic protein, which has been shown to be released from neurons. Here we provide evidence that extracellular Syn induces an increase in surface-exposed glucose-related protein of 78 kDa (GRP78), which becomes clustered in microdomains of the neuronal plasma membrane. Upon interacting with Syn, GRP78 activates a signaling cascade leading to cofilin 1 inactivation and stabilization of microfilaments, thus affecting morphology and dynamics of actin cytoskeleton in cultured neurons. Downregulation of GRP78 abolishes the activity of exogenous Syn, indicating that it is the primary target of Syn. Inactivation of cofilin 1 and stabilization of actin cytoskeleton are present also in fibroblasts derived from genetic PD patients, which show a dramatic increase in stress fibers. Similar changes are displayed by control cells incubated with the medium of PD fibroblasts, only when Syn is present. The accumulation of Syn in the extracellular milieu, its interaction with the plasma membrane and Syn-driven clustering of GRP78 appear, therefore, responsible for the dysregulation of actin turnover, leading to early deficits in synaptic function that precede neurodegeneration. PMID- 25124558 TI - Descriptive epidemiology of colorectal cancer in University Malaya Medical Centre, 2001 to 2010. AB - BACKGROUND: Colorectal cancer is the second most frequent cancer in Malaysia. Nevertheless, there is little information on treatment and outcomes nationally. We aimed to determine the demographic, clinical and treatment characteristics of colorectal cancer patients treated at the University Malaya Medical Centre (UMMC) as part of a larger project on survival and quality of life outcomes. MATERIALS AND METHODS: Medical records of 1,212 patients undergoing treatment in UMMC between January 2001 and December 2010 were reviewed. A retrospective-prospective cohort study design was used. Research tools included the National Cancer Patient Registration form. Statistical analysis included means, standard deviations (SD), proportions, chi square, t-test/ ANOVA. P-value significance was set at 0.05. RESULTS: The male: female ratio was 1.2:1. The mean age was 62.1 (SD12.4) years. Patients were predominantly Chinese (67%), then Malays (18%), Indians (13%) and others (2%). Malays were younger than Chinese and Indians (mean age 57 versus 62 versus 62 years, p<0.001). More females (56%) had colon cancers compared to males (44%) (p=0.022). Malays (57%) had more rectal cancer compared to Chinese (45%) and Indians (49%) (p=0.004). Dukes' stage data weres available in 67%, with Dukes' C and D accounting for 64%. Stage was not affected by age, gender, ethnicity or tumor site. Treatment modalities included surgery alone (40%), surgery and chemo/radiotherapy 32%, chemo and radiotherapy (8%) and others (20%). CONCLUSIONS: Significant ethnic differences in age and site distribution, if verified in population-based settings, would support implementation of preventive measures targeting those with the greatest need, at the right age. PMID- 25124559 TI - Review of the molecular pathogenesis of osteosarcoma. AB - Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA. PMID- 25124560 TI - TRAIL mediated signaling in pancreatic cancer. AB - Research over the years has progressively shown substantial broadening of the tumor necrosis factor alpha- related apoptosis-inducing ligand (TRAIL)-mediated signaling landscape. Increasingly it is being realized that pancreatic cancer is a multifaceted and genomically complex disease. Suppression of tumor suppressors, overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some of the extensively studied underlying mechanisms. Rapidly accumulating in vitro and in vivo evidence has started to shed light on the resistance mechanisms in pancreatic cancer cells. More interestingly a recent research has opened new horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus impairing processing of primary let-7. Xenografting DR5 silenced pancreatic cancer cells in SCID-mice indicated that there was notable suppression of tumor growth. There is a paradigm shift in our current understanding of TRAIL mediated signaling in pancreatic cancer cells that is now adding new layers of concepts into the existing scientific evidence. In this review we have attempted to provide an overview of recent advances in TRAIL mediated signaling in pancreatic cancer as evidenced byfindings of in vitro and in vivo analyses. Furthermore, we discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at target sites. PMID- 25124555 TI - KMTase Set7/9 is a critical regulator of E2F1 activity upon genotoxic stress. AB - During the recent years lysine methyltransferase Set7/9 ((Su(var)-3-9, Enhancer of-Zeste, Trithorax) domain containing protein 7/9) has emerged as an important regulator of different transcription factors. In this study, we report a novel function for Set7/9 as a critical co-activator of E2 promoter-binding factor 1 (E2F1)-dependent transcription in response to DNA damage. By means of various biochemical, cell biology, and bioinformatics approaches, we uncovered that cell cycle progression through the G1/S checkpoint of tumour cells upon DNA damage is defined by the threshold of expression of both E2F1 and Set7/9. The latter affects the activity of E2F1 by indirectly modulating histone modifications in the promoters of E2F1-dependent genes. Moreover, Set7/9 differentially affects E2F1 transcription targets: it promotes cell proliferation via expression of the CCNE1 gene and represses apoptosis by inhibiting the TP73 gene. Our biochemical screening of the panel of lung tumour cell lines suggests that these two factors are critically important for transcriptional upregulation of the CCNE1 gene product and hence successful progression through cell cycle. These findings identify Set7/9 as a potential biomarker in tumour cells with overexpressed E2F1 activity. PMID- 25124561 TI - Emerging and established global life-style risk factors for cancer of the upper aero-digestive tract. AB - INTRODUCTION: Upper aero-digestive tract cancer is a multidimensional problem, international trends showing complex rises and falls in incidence and mortality across the globe, with variation across different cultural and socio-economic groups. This paper seeks some explanations and identifies some research and policy needs. METHODOLOGICAL APPROACH: The literature illustrates the multifactorial nature of carcinogenesis. At the cellular level, it is viewed as a multistep process involving multiple mutations and selection for cells with progressively increasing capacity for proliferation, survival, invasion, and metastasis. Established and emerging risk factors, in addition to changes in incidence and prevalence of cancers of the upper aero-digestive tract, were identified. RISK FACTORS: Exposure to tobacco and alcohol, as well as diets inadequate in fresh fruits and vegetables, remain the major risk factors, with persistent infection by particular so-called "high risk" genotypes of human papillomavirus increasingly recognised as also playing an important role in a subset of cases, particularly for the oropharynx. Chronic trauma to oral mucosa from poor restorations and prostheses, in addition to poor oral hygiene with a consequent heavy microbial load in the mouth, are also emerging as significant risk factors. CONCLUSIONS: Understanding and quantifying the impact of individual risk factors for these cancers is vital for health decision-making, planning and prevention. National policies and programmes should be designed and implemented to control exposure to environmental risks, by legislation if necessary, and to raise awareness so that people are provided with the information and support they need to adopt healthy lifestyles. PMID- 25124562 TI - Functional roles of long non-coding RNA in human breast cancer. AB - The discovery of long noncoding RNA (LncRNA) changes our view of transcriptional and posttranscriptional regulation of gene expression. With application of new research techniques such as high-throughput sequencing, the biological functions of LncRNAs are gradually becoming to be understood. Multiple studies have shown that LncRNAs serve as carcinogenic factors or tumor suppressors in breast cancer with abnormal expression, prompts the question of whether they have potential value in predicting the stages and survival rate of breast cancer patients, and also as therapeutic targets. Focusing on the latest research data, this review mainly summarizes the tumorigenic mechanisms of certain LncRNAs in breast cancer, in order to provide a theoretical basis for finding safer, more effective treatment of breast cancer at the LncRNA molecular level. PMID- 25124563 TI - Critical review on the carcinogenic potential of pesticides used in Korea. AB - Pesticides used in Korea are grouped by four classes of hazard (extremely, highly, moderately and slightly hazardous) based on acute oral and dermal toxicity in the rat. However, there is little information of carcinogenic effects. The aim of this study was to evaluate potential carcinogenicity for active ingredients of pesticides used in Korea. A total of 1,283 pesticide items were registered under the Pesticide Control Act of which 987 were commercially available. Of these 987 items, 360 active ingredients not duplicated were evaluated for carcinogenicity using the carcinogen list established by the US Environmental Protection Agency (EPA). Some 25 out of 360 ingredients were classified as likely to be carcinogenic (probable) to humans and 52 had suggestive evidence of carcinogenic potential (suspected) based on the US EPA classification. Some 31% of 987 items contained probable or suspected human carcinogenic ingredients. Carcinogenic pesticides accounted for 24% (5,856/24,795 tons) of the total volume of consumption in Korea. Interestingly, pesticides with lower acute toxicity were found to have higher carcinogenic potential. Based on these findings, the study suggests that it is important to provide information on long-term toxicity to farmers, in addition to acute toxicity data. PMID- 25124564 TI - Comparison of recurrence rates with contour-loop excision of the transformation zone (C-LETZ) and large loop excision of the transformation zone (LLETZ) for CIN. AB - AIM: To compare recurrence rates of large loop excision of the transformation zone (LLETZ) with those of contour-loop excision of the transformation zone (C LETZ) in the management of cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: The medical records of 177 patients treated consecutively by LLETZ and C-LETZ for CIN at Rajavithi Hospital between 2006 and 2009 were retrospectively reviewed. RESULTS: Of the 87 women in the C-LETZ group, 2 cases (2.30%) had recurrence compared with 13 cases (14.4%) of the 90 women in the LLETZ group, the higher recurrence rate in the latter being statistically significant (p<0.05). Median times of follow up in the C-LETZ and LLETZ groups were 12 months and 14 months respectively (p>0.05). The C-LETZ group showed less intraoperative bleeding compared to the LLETZ group, but the rate of achievement of single specimens and positive margins were similar in the two groups. CONCLUSIONS: The present study demonstrated the superiority of C-LETZ over LLETZ in terms of efficacy; C-LLETZ is associated with a lower recurrence rate and also carries a smaller risk of intraoperative bleeding than LLETZ. The rotating technique still has a potential role in treating precancerous lesions of the cervix. PMID- 25124565 TI - Impact of cellular immune function on prognosis of lung cancer patients after cytokine-induced killer cell therapy. AB - AIMS: To investigate changes in cellular immune function of patients with lung cancer before and after cytokine- induced killer (CIK) cell therapy and to identify variation effects on overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: A total of 943 lung cancer patients with immune dysfunction were recruited from January 2002 to January 2010, 532 being allocated to conventional therapy and 411 to CIK therapy after a standard treatment according to the NCCN Clinical Practice Guidelines. All the patients were investigated for cellular immune function before and after therapy every three months. and clinical prognostic outcomes were analyzed. RESULTS: After six courses of treatment, immune function was much improved in patients receiving CIK cells therapy as compared to controls. The percentages of recurrence and/or metastases for patients undergoing CIK cell therapy was 56.2% and 49.1% respectively but 78.6% and 70.3% among controls (p<0.001). The median OS times for CIK cell therapy and control groups were 48 and 36 months respectively. The OS rates at 12, 36, 60, 84 months in CIK treated patients were 97.8%, 66.9%, 27.7%, and 4.1% while they were 92.3%, 44.5%, 9.2%, and 1.5% in controls. OS and PFS were significantly different by log rank test between the two groups and across the three immune improvement classes. CONCLUSIONS: The immune function of lung cancer patients was improved by CIK cell therapy, associated with an increase in the OS rate and extension of the time to recurrence and/or metastasis. PMID- 25124566 TI - Prognostic role of circulating tumor cells in patients with pancreatic cancer: a meta-analysis. AB - BACKGROUND: Isolation and characterization of circulating tumor cells (CTCs) in patients suffering from a variety of different cancers have become hot biomarker topics. In this study, we evaluated the prognostic value of CTCs in pancreatic cancer. MATERIALS AND METHODS: Initial literature was identified using Medline and EMBASE. The primary data were hazard ratios (HRs) with 95% confidence intervals (CIs) of survival outcomes, including overall survival (OS) and progression free survival/recurrence free survival (PFS/RFS). RESULTS: A total of 9 eligible studies were included in this meta-analysis, published between 2002 and 2013. The estimated pooled HR and 95%CI for OS for all studies was 1.64 (95%CI 1.39-1.94, p<0.00001) and the pooled HR and 95%CI for RFS/DFS was 2.36 (95%CI 1.41-3.96, p<0.00001). The HRs and 95%CIs for OS and RFS/ DFS in patients before treatment were 1.93 (95%CI 1.26-2.96, p=0.003) and 1.82 (95%CI 1.22-2.72, p=0.003), respectively. In patients receiving treatment, the HRs and 95%CI for OS and RFS/DFS were 1.37 (95%CI 1.00- 1.86, p=0.05) and 1.89 (95%CI 1.01-3.51, p=0.05), respectively. Moreover, the pooled HR and 95%CI for OS in the post treatment group was 2.20 (95%CI 0.80-6.02, p=0.13) and the pooled HR for RFS/DFS was 8.36 (95%CI 3.22-21.67, p<0.0001). CONCLUSIONS: The meta-analysis provided strong evidence supporting the proposition that CTCs detected in peripheral blood have a fine predictive role in pancreatic patients especially on the time point of post-treatment. PMID- 25124567 TI - Upregulation of STK15 in esophageal squamous cell carcinomas in a Mongolian population. AB - BACKGROUND: The STK15 gene located on chromosome 20q13.2 encodes a centrosome associated kinase critical for regulated chromosome segregation and cytokinesis. Recent studies have demonstrated STK15 to be significantly associated with many tumors, with aberrant expression obseved in many human malignancies. The purpose of this study was to investigate expression of STK15 in esophageal squamous cell carcinomas (ESCCs) in a Mongolian population. METHODS: Two non-synonymous single nucleotide polymorphisms in the coding region of STK15, rs2273535 (Phe31Ile) and rs1047972 (Val57Ile) were assessed in 380 ESCC patients and 380 healthy controls. We also detected STK15 mRNA expression in 39 esophageal squamous cell carcinomas and corresponding adjacent tissues by real time PCR. RESULTS: rs2273535 showed a significant association with ESCC in our Mongolian population (rs227353, P allele=0.0447, OR (95%CI)=1.259 (1.005~1.578)). Real time PCR analysis of ESCC tissues showed that expression of STK15 mRNA in cancer tissues was higher than in normal tissues (p=0.013). CONCLUSIONS: Our study showed that functional SNPs in the STK15 gene are associated with ESCC in a Mongolian population and up regulation of STK15 mRNAoccurs in ESCC tumors compared adjacent normal tissues. STK15 may thus have an important role in the prognosis of ESCC and be a potential therapeutic target. PMID- 25124568 TI - Survival analysis of biliary tract cancer cases in Turkey. AB - BACKGROUND: Because of the relative rarity of biliary tract cancers (BTCs), defining long term survival results is difficult. In the present study, we aimed to evaluate the survival of a series of cases in Turkey. MATERIALS AND METHODS: A totally of 47 patients with billiary tract cancer from Mersin Goverment Hospital, Acibadem Kayseri Hospital and Kayseri Training and Research Hospital were analyzed retrospectively using hospital records between 2006-2012. RESULTS: The median overall survival was 19.3+/-3.9 months for all patients. The median disease free and overall survivals were 24.3+/-5.3 and 44.1+/-12.9 months in patients in which radical surgery was performed , but in those with with inoperable disease they were only 5.3+/-1.5 and 10.7+/-3.2 months, respectively. CONCLUSIONS: BTCs have a poor prognosis. Surgery with a microscopic negative margin is still the only curative treatment. PMID- 25124569 TI - Comparison of survival rates between Chinese and Thai patients with breast cancer. AB - BACKGROUND: The burden and severity of a cancer can be reflected by patterns of survival. Breast cancer prognosis between two countries with a different socioeconomic status and cultural beliefs may exhibit wide variation. This study aimed to describe survival in patients with breast cancer in China and Thailand in relation to demographic and clinical prognostic information. MATERIALS AND METHODS: We compared the survival of 1,504 Chinese women in Yunnan province and 929 Thai women in Songkhla with breast cancer from 2006 to 2010. Descriptive prognostic comparisons between the Chinese and Thai women were performed by relative survival analysis. A Cox regression model was used to calculate the hazard ratios of death, taking into account the age, disease stage, period of diagnosis and country. RESULTS: The overall 5-year survival proportion for patients diagnosed with breast cancer for Yunnan province (0.72) appeared slightly better than Songkhla (0.70) without statistical significance. Thai women diagnosed with distant and regional breast cancer had poorer survival than Chinese women. Disease stage was the most important determinant of survival from the results of Cox regression model. CONCLUSIONS: Breast cancer patients in Kunming had slightly greater five-year survival rate than patients in Songkhla. Both Chinese and Thai women need improvement in prognosis, which could conceivably be attained through increased public education and awareness regarding early detection and compliance to treatment protocols. PMID- 25124570 TI - Parathyroid hormone gene rs6256 and calcium sensing receptor gene rs1801725 variants are not associated with susceptibility to colorectal cancer in Iran. AB - BACKGROUND: Substantial evidence from epidemiological studies has suggested that increased levels of calcium may play a protective role against colorectal cancer (CRC). Given the vital role of calcium sensing receptor (CaSR) and parathyroid hormone (PTH) in the maintenance of calcium homeostasis, we explored whether the rs1801725 (A986S) variant located in exon 7 of the CaSR gene and the rs6256 variant located in exon 3 of PTH gene might be associated with CRC risk. MATERIALS AND METHODS: In this study 860 subjects including 350 cases with CRC and 510 controls were enrolled and genotyped using PCR-RFLP methods. RESULTS: We observed no significant difference in genotype or allele frequencies between the cases with CRC and controls for both CaSR and PTH genes either before or after adjustment for confounding factors including age, BMI, sex, smoking status, and family history of CRC. Furthermore, no evidence for effect modification of any association of rs1801725 and rs6256 variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI<25 kg/m2) cases and overweight/ obese (BMI>=25 kg/m2) cases for the two SNPs. CONCLUSIONS: These data indicated that the CaSR gene A986S variant is not a genetic contributor to CRC risk in the Iranian population. Furthermore, our results suggest for the first time that PTH gene variant does not affect CRC risk. Nonetheless, further studies with larger sample size are needed to validate these findings. PMID- 25124572 TI - Weight loss correlates with macrophage inhibitory cytokine-1 expression and might influence outcome in patients with advanced esophageal squamous cell carcinoma. AB - BACKGROUND: Weight loss during chemotherapy has not been exclusively investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its etiology. Here, we investigated the prognostic value of weight loss before chemotherapy and its relationship with MIC-1 concentration and its occurrence during chemotherapy in patients with advanced esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: We analyzed 157 inoperable locally advanced or metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1 concentrations were assessed before chemotherapy. Patients were assigned into two groups according to their weight loss before or during chemotherapy: >5% weight loss group and<=5% weight loss group. RESULTS: Patients with weight loss>5% before chemotherapy had shorter progression-free survival period (5.8 months vs. 8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010). Patients with weight loss>5% during chemotherapy tended to have shorter progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed during chemotherapy, survival rates improved. Furthermore, serum MIC-1 concentration was closely related to weight loss before chemotherapy (p=0.001) CONCLUSIONS: Weight loss both before and during chemotherapy predicted poor outcome in advanced ESCC patients, and MIC-1 might be involved in the development of weight loss in such patients. PMID- 25124571 TI - Computed tomography manifestations of histologic subtypes of retroperitoneal liposarcoma. AB - OBJECTIVE: Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts for approximately 20% of all mesenchymal malignancies, often occurring in deep soft tissue of retroperitoneal space. Accurate preoperative diagnosis is therefore necessary. We explored whether computed tomography (CT) could be used to differentiate between the various types of retroperitoneal liposarcoma (RPLS). METHOD: Forty-seven cases of RPLS, diagnosed surgically and histologically, were analyzed retrospectively. CT features were correlated with postoperative pathological appearance. RESULTS: The study radiologist identified 29, 11, 2, 2 and 3 RPLS as atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), dedifferentiated liposarcoma (DDL), myxoid/round cell liposarcoma (ML/RCL), pleomorphic liposarcoma (PL) and mixed-type liposarcoma. Analysis of CT scans revealed the following typical findings of the different subtypes of RPLS: ALT/WDL was mainly visible as a well-delineated fatty hypodense tumor with uniform density and integrity margin; DDL was marked by the combination of focal nodular density and hypervascularity. ML/RCL, PL and mixed liposarcoma showed malignant biological behaviour and CT findings need further studies. CONCLUSIONS: CT scanning can reveal important details including internal components, margins and surrounding tissues. Based on CT findings, tumor type can be roughly evaluated and biopsy location and therapeutic scheme guided. PMID- 25124573 TI - Utility of frozen section pathology with endometrial pre-malignant lesions. AB - AIM: To determine utility of the frozen section (FS) in the operative management of endometrial pre-malignant lesions. MATERIALS AND METHODS: We retrospectively analyzed patients who underwent abdominal hysterectomy with preoperative diagnosis of complex atypical endometrial hyperplasia (CAEH) and simple endometrial hyperplasia (SEH) between May 2007 and December 2013. Frozen and paraffin section (PS) results were compared. Sensitivity, specificity, the positive predictive value (PPV), the negative predictive value (NPV) and the accuracy in predicting EC on FS were evaluated with 95% confidence intervals (CIs) for each parameter. The correlation between FS and PS was calculated as an kappa coefficient. RESULTS: Among 143 preoperatively diagnosed CAEH cases, 60 (42%) were malignant and 83 (58%) were benign in PS; and among 60 malignant cases diagnosed in PS, 43 (71%) were "malignant" in FS. Sensitivity, specificity, PPV and NPV for FS were 76%, 100%, 100% and 87.5%, respectively. CONCLUSIONS: We found that FS is reliable and applicable in the management of endometrial hyperplasias. It is important that the pathologist should be experienced because FS for endometrial pre-malignant lesions has significant inter-observer variability. The other conclusion is that patients with the diagnosis of EH, especially those who are postmenopausal, should undergo surgery where FS investigation is available. PMID- 25124574 TI - SLC35B2 expression is associated with a poor prognosis of invasive ductal breast carcinoma. AB - BACKGROUND: Breast cancer is the most common malignancy in women worldwide, including Thailand, and is a major cause of mortality and morbidity, despite advances in diagnosis and treatment. Novel gene expression in breast cancer is a focus in searches for prognostic biomarkers and new therapeutic targets. MATERIALS AND METHODS: The mRNA expression of novel B4GALT4, SLC35B2, and WDHD1 genes in breast cancer were examined in invasive ductal breast carcinoma (IDC) patients using quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR). RESULTS: Among these genes, increased expression of SLC35B2 mRNA was significantly associated with TNM stage III+IV of IDC (p<0.001). Hence, up-regulation of SLC35B2 may serve as a prognostic biomarker for poor prognosis, and is also a potential therapeutic target in breast cancer. PMID- 25124576 TI - Distinct pro-apoptotic properties of Zhejiang saffron against human lung cancer via a caspase-8-9-3 cascade. AB - Lung cancer is the leading cause of cancer-related death worldwide. Here we investigated the antitumor effect and mechanism of Zhejiang (Huzhou and Jiande) saffron against lung cancer cell lines, A549 and H446. Using high performance liquid chromatography (HPLC), the contents of crocin I and II were determined. In vitro, MTT assay and annexin-V FITC/PI staining showed cell proliferation activity and apoptosis to be changed in a dose- and time-dependent manner. The inhibition effect of Jiande saffron was the strongest. In vivo, when mice were orally administered saffron extracts at dose of 100mg/kg/d for 28 days, xenograft tumor size was reduced, and ELISA and Western blotting analysis of caspase-3, -8 and -9 exhibited stronger expression and activity than in the control. In summary, saffron from Zhejiang has significant antitumor effects in vitro and in vivo through caspase-8-caspase-9-caspase-3 mediated cell apoptosis. It thus appears to have more potential as a therapeutic agent. PMID- 25124575 TI - Association of Rs11615 (C>T) in the excision repair cross-complementing group 1 gene with ovarian but not gynecological cancer susceptibility: a meta-analysis. AB - BACKGROUND: Evidence suggests that the rs11615 (C>T) polymorphism in the ERCC1 gene may be a risk factor for gynecological tumors. However, results have not been consistent. Therefore we performed this meta- analysis. METHODS: Eligible studies were identified by search of PubMed, MEDLINE and Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess associations between rs11615 (C>T) and gynecological tumor risk. Heterogeneity among studies was tested and sensitivity analysis was applied. RESULTS: A total of 6 studies were identified, with 1,766 cases and 2,073 controls. No significant association was found overall between the rs11615 (C>T) polymorphism and gynecological tumor susceptibility in any genetic model. In further analysis stratified by cancer type, significantly elevated ovarian cancer risk was observed in the homozygote and recessive model comparison (TT vs CC: OR=1.69, 95% CI=1.03-2.77, heterogeneity=0.876; TT vs CT/CC: OR=1.72, 95% CI=1.07-2.77, heterogeneity=0.995). CONCLUSION: The results of the present meta analysis suggest that there is no significant association between the rs11615 (C>T) polymorphism and gynecological tumor risk, but it had a increased risk in ovarian cancer. PMID- 25124577 TI - Effectiveness of the Microlux/DLTM chemiluminescence device in screening of potentially malignant and malignant oral lesions. AB - BACKGROUND: To evaluate the effectiveness of Microlux/DL with and without toluidine blue in screening of potentially malignant and malignant oral lesions. MATERIALS AND METHODS: In this diagnostic clinical trial clinical examination was carried out by two teams: 1) two oral medicine consultants, and 2) two general dentists. Participants were randomly and blindly allocated for each examining team. A total of 599 tobacco users were assessed through conventional oral examination (COE); the examination was then repeated using Microlux/DL device and toluidine blue. Biopsy of suspicious lesions was performed. Also clinicians opinions regarding the two tools were obtained. RESULTS: The sensitivity and, specificity and positive predictive value (PVP) of Microlux/DL for visualization of suspicious premalignant lesions considering COE as a gold standard (i.e screening device) were 94.3%, 99.6% and 96.2% respectively, while they were 100%, 32.4% and 17.9% when considering biopsy as a gold standard. Moreover, Microlux/DL enhanced detection of the lesion and uncovered new lesions compared to COE, whereas it did not alter the provisional clinical diagnosis, or alter the biopsy site. On the other hand, adding toluidine blue dye did not improve the effectiveness of the Microlux/DL system. CONCLUSIONS: The Microlux/DL seems to be a promising adjunctive screening device. PMID- 25124578 TI - Impact of prognostic factors on survival rates in patients with ovarian carcinoma. AB - PURPOSE: The aim of the present study was to invesitigate the impact of significant clinico-pathological prognostic factors on survival rates and to identify factors predictive of poor outcome in patients with ovarian carcinoma. MATERIALS AND METHODS: A retrospective chart review of 74 women with pathologically proven ovarian carcinoma who were treated between January 2006 and April 2011 was performed. Patients were investigated with respect to survival to find the possible effects of age, gravida, parity, menstruel condition, pre operative Ca-125, treatment period, cytologic washings, presence of ascites, tumor histology, stage and grade, maximal tumor diameter, adjuvan chemotherapy and cytoreductive success. Also 55 ovarian carcinoma patients were investigated with respect to prognostic factors for early 2-year survival. RESULTS: The two year survival rate was 69% and the 5-year survival rate was 25.5% for the whole study population. Significant factors for 2-year survival were preoperative CA 125 level, malignant cytology and FIGO clinical stage. Significant factors for 5 year survival were age, preoperative CA-125 level, residual tumor, lymph node metastases, histologic type of tumor, malignant cytology and FIGO clinical stage. Logistic regression revealed that independent prognostic factors of 5-year survival were patient age, lymph node metastasis and malignant cytology. CONCLUSIONS: We consider quality registries with prospectively collected data to be one important tool in monitoring treatment effects in population-based cancer research. PMID- 25124579 TI - Perception and practices on screening and vaccination for carcinoma cervix among female healthcare professional in tertiary care hospitals in Bangalore, India. AB - BACKGROUND: Cervical cancer is potentially the most preventable and treatable cancer. Despite the known efficacy of cervical screening, a significant number of women do not avail themselves of the procedure due to lack of awareness. OBJECTIVES: This study was conducted to elicit information on the knowledge, attitude and practice (KAP) regarding screening (Pap test) and vaccination for carcinoma cervix among female doctors and nurses in a tertiary care hospital in Bangalore and to assess barriers to acceptance of the Pap test. MATERIALS AND METHODS: A cross-sectional, descriptive study was conducted with semi-structured, self-administered questionnaire among female health professionals. The study subjects were interviewed for KAP regarding risk factors for cancer cervix, Pap test and HPV vaccination for protection against carcinoma cervix. RESULTS: Higher proportion of doctors 45 (78.9%) had very good knowledge as compared to only 13 (13.3%) of the nurses, about risk factors for cancer cervix and Pap test (p=0.001). As many as 138(89.6%) of the study subjects had favorable attitude towards Pap test and vaccination, but 114 (73.6%) of the study subjects never had a Pap test and the most common reason 35 (31%) for not practicing was absence of disease symptoms. CONCLUSIONS: In spite of good knowledge and attitudes towards cancer cervix and Pap test being good, practice remained low among the study subjects and most common reasons for not undergoing Pap test was absence of disease symptoms. The independent predictors of ever having a Pap test done was found to be the occupation and duration of married life above 9 yrs. Hence there is a strong need to improve uptake of Pap test by health professionals by demystifying the barriers. PMID- 25124580 TI - Elevated serum ferritin levels in patients with hematologic malignancies. AB - PURPOSE: To retrospectively analyze variability and clinical significance of serum ferritin levels in Chinese patients with hematologic malignancies. MATERIALS AND METHODS: Serum ferritin were measured by radioimmunoassay, using a kit produced by the Beijing Institute of Atomic Energy. Patients with hematologic malignancies, and treated in the Department of Hematology in Nanjing First Hospital and fulfilled study criteria were recruited. RESULTS: Of 473 patients with hematologic malignancies, 262 patients were diagnosed with acute leukemia, 131 with lymphoma and 80 with multiple myeloma. Serum ferritin levels of newly diagnosed and recurrent patients were significantly higher than those entering complete remission stage or in the control group (p<0.001). CONCLUSIONS: Serum ferritin lever in patients with hematologic malignancies at early stage and recurrent stage are significantly increased, so that detection and surveillance of changes of serum ferritin could be helpful in assessing conditions and prognosis of this patient cohort. PMID- 25124581 TI - Prognostic significance of beta-catenin expression in patients with esophageal carcinoma: a meta-analysis. AB - Many studies have reported beta-catenin involvement in the development of esophageal carcinoma (EC), but its prognostic significance for EC patients remains controversial. Therefore, we conducted this meta-analysis to explore the issue in detail. After searching PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature Database, we included a total of ten relevant studies. We pooled the overall survival (OS) data using RevMan 5.2 software. The results showed that aberrant expression of beta-catenin was associated with a significant increase of mortality risk (hazard ratio 1.71, 95%CI 1.46-2.01; p<0.00001). Subgroup analyses further suggested that aberrant expression of beta-catenin resulted in poor OS of EC patients regardless of histological type of EC, study location or criteria for aberrant expression of beta-catenin, and the sensitivity analyses revealed that the result was robust. The meta-analysis revealed that aberrant expression of beta-catenin could be a predicative factor of poor prognosis for EC patients. PMID- 25124582 TI - Clinicopathological features of indonesian breast cancers with different molecular subtypes. AB - BACKGROUND: Breast cancer is a heterogeneous disease with molecular subtypes that have biological distinctness and different behavior. They are classified into luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes. Most of breast cancers reported in Indonesia are already large size, with high grade or late stage but the clinicopathological features of different molecular subtypes are still unclear. They need to be better clarified to determine proper treatment and prognosis. AIM: To elaborate the clinicopathological features of molecular subtypes of breast cancers in Indonesian women. MATERIALS AND METHODS: A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast cancer samples from Dr. Sardjito General Hospital in Central Java, Indonesia was performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify molecular subtypes of breast cancer by immunohistochemistry. The relation of clinicopathological features of breast cancers with molecular subtypes of luminal A, luminal B, Her-2 and triple negative/basal-like were analyzed using Pearson's Chi-Square test. A p-value of <0.05 was considered statistically significant. RESULTS: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant difference was found in breast cancer molecular subtypes in regard to age, histological grade, lymph node status and staging. However it showed insignificant result in regard to tumor size. Luminal A subtype of breast cancer was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09), negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the difference was insignificant, luminal A subtype breast cancer was mostly found in small size breast cancer (p:0.129). Her-2+ subtype breast cancer was more commonly diagnosed with large size, positive lymph node metastasis and poor grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old women. CONCLUSIONS: This study suggests that immunohistochemistry-based subtyping is essential to classify breast carcinoma into subtypes that vary in clinicopathological features, implying different therapeutic options and prognosis for each subtype. PMID- 25124583 TI - Comparisons between the KKU-model and conventional rectal tubes as markers for checking rectal doses during intracavitary brachytherapy of cervical cancer. AB - BACKGROUND: To compare the KKU-model rectal tube (KKU-tube) and the conventional rectal tube (CRT) for checking rectal doses during high-dose-rate intracavitary brachytherapy (HDR-ICBT) of cervical cancer. MATERIALS AND METHODS: Between February 2010 and January 2011, thirty -two patients with cervical cancer were enrolled and treated with external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT). The KKU-tube and CRT were applied intrarectally in the same patients at alternate sessions as references for calculation of rectal doses during ICBT. The gold standard references of rectum anatomical markers which are most proximal to radiation sources were anterior rectal walls (ARW) adjacent to the uterine cervix demonstrated by barium sulfate suspension enema. The calculated rectal doses derived from actual anterior rectal walls, CRT and the anterior surfaces of the KKU-tubes were compared by using the paired t-test. The pain caused by insertion of each type of rectal tube was assessed by the visual analogue scale (VAS). RESULTS: The mean dose of CRT was lower than the mean dose of ARW (Dmean0-Dmean1) by 80.55+/-47.33 cGy (p-value<0.05). The mean dose of the KKU-tube was lower than the mean dose of ARW (Dmean0-Dmean2) by 30.82+/-24.20 cGy (p-value<0.05). The mean dose difference [(Dmean0-Dmean1)-(Dmean0-Dmean2)] was 49.72+/-51.60 cGy, which was statistically significant between 42.32 cGy -57.13 cGy with the t-value of 13.24 (p-value<0.05). The maximum rectal dose by using CRT was higher than the KKU-tube as much as 75.26 cGy and statistically significant with the t-score of 7.55 (p-value<0.05). The mean doses at the anterior rectal wall while using the CRTs and the KKU-tubes were not significantly different (p-value=0.09). The mean pain score during insertion of the CRT was significantly higher than the KKU-tube by a t-score of 6.15 (p value<0.05) CONCLUSIONS: The KKU-model rectal tube was found to be an easily producible, applicable and reliable instrument as a reference for evaluating the rectal dose during ICBT of cervical cancer without negative effects on the patients. PMID- 25124584 TI - Prostate-specific antigen levels in relation to background factors: are there links to endocrine disrupting chemicals and AhR expression? AB - BACKGROUND: Prostate-specific antigen (PSA) is a potential biomarker for early detection of prostate cancer (PCa) but its level is known to be affected by many background factors and roles of ubiquitous toxicants have not been determined. Endocrine disrupting chemicals (EDCs) are ubiquitous reproductive toxicants used in consumer products, which promote tumor formation in some reproductive model systems by binding to AhR, but human data on its expression in prostate cancer as well as its association with PSA levels are not clear. This study aimed to evaluate the expression levels of AhR and its association with serological levels of PSA and to detect possible effects of background factors and EDC exposure history on PSA levels in PCa cases. MATERIALS AND METHODS: A cross-sectional study was conducted on the tissue levels of AhR and serum levels of PSA in 53 PCa cases from 2008-2011 and associations between each and background and lifestyle related factors were determined. RESULTS: Although the AhR was overexpressed in PCa and correlated with the age of patients, it did not correlate with PSA levels.Of nutritional factors, increased intake of polysaturated fats and fish in the routine regimen of PCa cases increased the PSA levels significantly. CONCLUSIONS: AhR overexpression in PCa pontws to roles of EDCs in PCa but without any direct association with PSA levels. However, PSA levels are affected by exposure to possible toxicants in foods whichneed to be assessed as possible risk factors of PCa in future studies. PMID- 25124585 TI - Allogeneic hemopietic stem cell transplants for the treatment of B cell acute lymphocytic leukemia. AB - OBJECTIVE: Explore the feasibility of allo- hemopietic stem cell transplants in treating patients with B cell acute lymphocytic leukemia. METHODS: Between september 2006 and February 2011, fifteen patients with B cell acute lymphocytic leukemia (ALL) were treated by allo-hemopietic stem cell transplants (HSCT). Stem cell sources were peripheral blood. Six patients were conditioned by busulfan (BU) and cyclophosphamide (CY) and nine patients were conditioned with TBI and cyclophosphamide (CY). Graft versus host disease (GVHD) prophylaxis regimen consisted of cyclosporine A (CSA), methotrex ate (MTX) and mycophenolatemofetil (MMF). RESULTS: Patients received a median of 7.98*108.kg-1 (5.36-12.30*108.kg-1) mononuclear cells (MNC). The median time of ANC>0.5*109/L was day 12 (10-15), and PLT>20.0*109/L was day 13 (11-16). Extensive acute GVHD occurred in 6 (40.0%) patients, and extensive chronic GVHD was recorded in 6 (40.0%) patients. Nine patients were alive after 2.5-65 months follow-up. CONCLUSION: Allogeneic stem cell transplant could be effective in treating patients with B cell acute lymphocytic leukemia. PMID- 25124586 TI - Lack of any association of GST genetic polymorphisms with susceptibility to ovarian cancer--a meta-analysis. AB - OBJECTIVE: Epidemiology studies have reported conflicting results between glutathione S-transferase Mu-1 (GSTM1), glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase pi-1 (GSTP1) and ovarian cancer (OC) susceptibility. In this study, an updated meta-analysis was applied to determine whether the deletion of GSTM1, GSTT1 and GSTP1 has an influence on OC susceptibility. METHODS: A published literature search was performed through PubMed, Embase, Cochrane Library, and Science Citation Index Expanded database for articles published in English. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random or fixed effects models. Heterogeneity between studies was assessed using the Cochrane Q test and I2 statistics. Sub-group analysis was conducted to explore the sources of heterogeneity. Sensitivity analysis was employed to evaluate the respective influence of each study on the overall estimate. RESULTS: In total, 10 published studies were included in the final analysis. The combined analysis revealed that there was no significant association between GSTM1 null genotype and OC risk (OR=1.01, 95%CI: 0.91-1.12). Additionally, there was no significant association between GSTT1 genetic polymorphisms and OC risk (OR=0.98, 95% CI: 0.85-1.13). Similalry, no significant associations were found concerning the GSTP1 rs1695 locus and OC risk. Meanwhile, subgroup analysis did not show a significant increase in eligible studies with low heterogeneity. However, sensitivity analysis, publication bias and cumulative analysis demonstrated the reliability and stability of the current meta-analysis. CONCLUSIONS: These findings suggest that GSTs genetic polymorphisms may not contribute to OC susceptibility. Large epidemiological studies with the combination of GSTM1 null, GSTT1 null and GSTP1 Ile105Val polymorphisms and more specific histological subtypes of OC are needed to prove our findings. PMID- 25124587 TI - Serum adiponectin but not leptin at diagnosis as a predictor of breast cancer survival. AB - Limited numbers of epidemiological studies have examined the relationship between adipokines and breast cancer survival. Preoperative serum levels of obesity related adipokines (leptin and adiponectin) were here measured in 370 breast cancer patients, recruited from two hospitals in Korea. We examined the association between those adipokines and disease-free survival (DFS). The TNM stage, ER status and histological grade were aslo assessed in relation to breast cancer survival. Elevated adiponectin levels were associated with reduced DFS of breast cancer (Ptrend=0.03) among patients with normal body weight, predominantly in postmenopausal women. There was no association of leptin with breast cancer survival. In conclusion, our study suggests that high levels of adiponectin at diagnosis are associated with breast cancer survival among women with normal body weight. PMID- 25124588 TI - Expression of Toll-like receptor 9 increases with progression of cervical neoplasia in Tunisian women--a comparative analysis of condyloma, cervical intraepithelial neoplasia and invasive carcinoma. AB - Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked to a persistent infection with high risk human papillomaviruses (HR-HPVs) and could be associated with alteration of TLRs expression. TLR9 plays a key role in the recognition of DNA viruses and better understanding of this signaling pathway in CC could lead to the development of novel immunotherapeutic approaches. The present study was undertaken to determine the level of TLR9 expression in cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18 of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical tissues as control cases. Quantification of TLR9 expression was based on scoring four degrees of extent and intensity of immunostaining in squamous epithelial cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2 (83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9 expression were compared using the Kruskall-Wallis test and there was a statistical significance between normal tissue and condyloma as well as between condyloma, CINs and ICC. These results suggest that TLR9 may play a role in progression of cervical neoplasia in Tunisian patients and could represent a useful biomarker for malignant transformation of cervical squamous cells. PMID- 25124589 TI - Prevalence and genotype distribution of HPV among women attending a cervical cancer screening mobile unit in Lampang, Thailand. AB - A growing body of literature is evidence that identifying subtypes of high-risk human papillomavirus (HR-HPV) has impacted on various steps of cervical cancer prevention.Thus, it is mandatory to determine the background prevalence and distribution of HPV subtypes for designing and implementing area-specific management. The present study was conducted to evaluate prevalence and distribution of HPV subtypes among women aged 30-70 years living in Lampang, an area with a high incidence of cervical cancer, through use of a mobile screening unit. Of 2,000 women recruited in this study, 108 (5.40%, 95%CI: 4.45-6.48) were found to have HR-HPV infection. Risk was significantly correlated with age and number of partners. Singly or in combination, the most common genotype was HPV 52 (17.6%), followed by HPV 16 (14.81%), HPV 58 (13.89%), HPV 33 (11.11%), HPV 51 (11.11%), and HPV 56 (9.26%). HPV 18 was found in only 5.6% of cases. Together, HPV 16/18 were noted in approximately 20.4% of cases. Eighteen(16.67%) women were positive with multiple subtypes of HR-HPV. Co-infection most frequently involved HPV 16 or HPV 58. These findings have obvious implications for vaccine policy. PMID- 25124590 TI - Diffusion-weighted imaging for the left hepatic lobe has higher diagnostic accuracy for malignant focal liver lesions. AB - BACKGROUND: This study was conducted to investigate whether apparent diffusion coefficient (ADC) measurements by dividing the liver into left and right hepatic lobes may be utilized to improve the accuracy of differential diagnosis of benign and malignant focal liver lesions. MATERIALS AND METHODS: A total of 269 consecutive patients with 429 focal liver lesions were examined by 3-T magnetic resonance imaging that included diffusion-weighted imaging. For 58 patients with focal liver lesions of the same etiology in left and right hepatic lobes, ADCs of normal liver parenchyma and focal liver lesions were calculated and compared using the paired t-test. For all 269 patients, ADC cutoffs for focal liver lesions and diagnostic accuracy in the left hepatic lobe, right hepatic lobe and whole liver were evaluated by receiver operating characteristic curve analysis. RESULTS: For the group of 58 patients, mean ADCs of normal liver parenchyma and focal liver lesions in the left hepatic lobe were significantly higher than those in the right hepatic lobe. For differentiating malignant lesions from benign lesions in all patients, the sensitivity and specificity were 92.6% and 92.0% in the left hepatic lobe, 94.4% and 94.4% in the right hepatic lobe, and 90.4% and 94.7% in the whole liver, respectively. The area under the curve of the right hepatic lobe, but not the left hepatic lobe, was higher than that of the whole liver. CONCLUSIONS: ADCs of normal liver parenchyma and focal liver lesions in the left hepatic lobe were significantly higher than those in the right hepatic lobe. Optimal ADC cutoff for focal liver lesions in the right hepatic lobe, but not in the left hepatic lobe, had higher diagnostic accuracy compared with that in the whole liver. PMID- 25124591 TI - Radiation induces phosphorylation of STAT3 in a dose- and time-dependent manner. AB - BACKGROUND: We have reported the radiation could activate STAT3, which subsequently promotes the invasion of A549 cells. We here explored the dose- and time-response of STAT3 to radiation and the effect of radiation on upstream signaling molecules. MATERIALS AND METHODS: A549 cells were irradiated with different doses of gamma-rays. The expression of and nucleus translocation of p STAT3 in A549 cells were detected by immunoblotting and immunofluorescence, respectively. The level of phosphorylated EGFR was also assessed by immunoblotting, and IL-6 expression was detected by real time PCR and ELISA. RESULTS: Radiation promoted the phosphorylation of STAT3 at Y705 in a dose- and time-dependent manner and nuclear translocation. The level of phosphorylated EGFR in A549 cells increased after radiation. In additional, the mRNA and protein levels of IL-6 in A549 cells were also up regulated by radiation. CONCLUSIONS: STAT3 is activated by radiation in a dose-and time-dependent manner, probably due to radiation-induced activation of EGFR or secretion of IL-6 in A549 cells. PMID- 25124592 TI - Intra-peritoneal cisplatin combined with intravenous paclitaxel in optimally debulked stage 3 ovarian cancer patients: an Izmir Oncology Group study. AB - BACKGROUND: The advantage of intra-peritoneal (IP) chemotherapy (CT) in the initial management of ovarian cancer after cytoreductive surgery is well known. The feasibility and toxicity of a treatment regimen with an IP+intravenous CT (IPIVCT) for optimally debulked stage III ovarian cancer were here evaluated retrospectively. MATERIALS AND METHODS: A total of 30 patients were treated in our institution between October 2006 and February 2011. Patients received IV paclitaxel 175 mg/m2 over 3 hours followed by IP cisplatin 75 mg/m2 on day 1; they also received IP paclitaxel 60 mg/m2 on day 8. They were also scheduled to receive 6 courses of CT every 21 days. RESULTS: The median age of the patients was 55 years (35-77), and the majority had papillary serous ovarian cancer (63.3%). The patients completed a total of 146 cycles of IPIVCT. Twenty-eight were able to receive at least three cycles of IPIVCT and 18 (60%) completed the scheduled 6 cycles. Two patients discontinued the IPIVCT because of toxicity of chemotherapy agents and 6 had to stop treatment due to intolerable abdominal pain during IP drug administration, obstruction and impaired access. Grade 3/4 toxicities included neutropenia (6 patients; 20%), anemia (2 patients; 6.7%) and nausea-vomiting (2 patients; 6.7%). Doses were delayed in 12 cycles (8%) for neutropenia (n=6), thrombocytopenia (n=3) and elevated creatinine (n=3). Drug doses were not reduced. The median duration of progression-free survival (PFS) was 47.7 months (95%CI, 38.98-56.44) and overall survival (OS) was 51.7 months (95%CI, 44.13-59.29). Two and five-year overall survival rates were 75.6 % and 64.8%, respectively. CONCLUSIONS: IPIVCT is feasible and well-tolerated in this setting. Its clinically proven advantages should be taken into consideration and more efforts should be made to administer IPIVCT to suitable patients. PMID- 25124593 TI - In whom do cancer survivors trust online and offline? AB - BACKGROUND: In order to design effective educational intervention for cancer survivors, it is necessary to identify most-trusted sources for health-related information and the amount of attention paid to each source. OBJECTIVE: The objective of our study was to explore the sources of health information used by cancer survivors according to their access to the internet and levels of trust in and attention to those information sources. MATERIALS AND METHODS: We analyzed sources of health information among cancer survivors using selected questions adapted from the 2012 Health Information National Trends Survey (HINTS). RESULTS: Of 357 participants, 239 (67%) had internet access (online survivors) while 118 (33%) did not (offline survivors). Online survivors were younger (p<0.001), more educated (p<0.001), more non-Hispanic whites (p<0.001), had higher income (p<0.001), had more populated households (p<0.001) and better quality of life (p<0.001) compared to offline survivors. Prevalence of some disabilities was higher among offline survivors including serious difficulties with walking or climbing stairs (p<0.001), being blind or having severe visual impairment (p=0.001), problems with making decisions (p<0.001), doing errands alone (p=0.001) and dressing or bathing (p=0.001). After adjusting for socio- demographic status, cancer survivors who were non-Hispanic whites (OR=3.49, p<0.01), younger (OR=4.10, p<0.01), more educated (OR=2.29, p=0.02), with greater income (OR=4.43, p<0.01), and with very good to excellent quality of life (OR=2.60, p=0.01) had higher probability of having access to the internet, while those living in Midwest were less likely to have access (OR=0.177, p<0.01). Doctors (95.5%) were the most and radio (27.8%) was the least trusted health related information source among all cancer survivors. Online survivors trusted internet much more compared to those without access (p<0.001) while offline cancer survivors trusted health-related information from religious groups and radio more than those with internet access (p<0.001 and p=0.008). Cancer survivors paid the most attention to health information on newsletters (63.8%) and internet (60.2%) and the least to radio (19.6%). More online survivors paid attention to internet than those without access (68.5% vs 39.1%, p<0.001) while more offline survivors paid attention to radio compared to those with access (26.8% vs 16.5%, p=0.03). CONCLUSIONS: Our findings emphasize the importance of improving the access and empowering the different sources of information. Considering that the internet and web technologies are continuing to develop, more attention should be paid to improve access to the internet, provide guidance and maintain the quality of accredited health information websites. Those without internet access should continue to receive health-related information via their most trusted sources. PMID- 25124594 TI - HPV vaccination for cervical cancer prevention is not cost-effective in Japan. AB - BACKGROUND: Our study objectives were to evaluate the medical economics of cervical cancer prevention and thereby contribute to cancer care policy decisions in Japan. METHODS: Model creation: we created presence- absence models for prevention by designating human papillomavirus (HPV) vaccination for primary prevention of cervical cancer. Cost classification and cost estimates: we divided the costs of cancer care into seven categories (prevention, mass-screening, curative treatment, palliative care, indirect, non-medical, and psychosocial cost) and estimated costs for each model. Cost-benefit analyses: we performed cost-benefit analyses for Japan as a whole. RESULTS: HPV vaccination was estimated to cost $291.5 million, cervical cancer screening $76.0 million and curative treatment $12.0 million. The loss due to death was $251.0 million and the net benefit was -$128.5 million (negative). CONCLUSION: Cervical cancer prevention was not found to be cost-effective in Japan. While few cost-benefit analyses have been reported in the field of cancer care, these would be essential for Japanese policy determination. PMID- 25124596 TI - Knowledge, perceptions and acceptability of HPV vaccination among medical students in Chongqing, China. AB - OBJECTIVES: To evaluate medical students' knowledge of HPV and HPV related diseases and assess their attitudes towards HPV vaccination. METHODS: A total of 605 medical undergraduates from Chongqing Medical University in China were surveyed using a structured and pretested questionnaire on HPV related knowledge. RESULTS: Some 68.9% of the medical students were females, and mean age was 21.6 (+/-1.00) years. Only 10.6% correctly answered more than 11 out of 14 questions on HPV related knowledge, 71.8% being willing to receive/ advise on HPV vaccination. Female students (OR: 2.69; 95% CI: 1.53-4.72) and students desiring more HPV education (OR: 4.24; 95% CI: 1.67-10.8) were more willing to accept HPV vaccination. HPV vaccination acceptability was observed to show a positive association with HPV related knowledge. CONCLUSIONS: Our survey found low levels of HPV related knowledge and HPV vaccination acceptability among participating medical students. HPV education should be systematically incorporated into medical education to increase awareness of HPV vaccination. PMID- 25124595 TI - Lack of associations of the COMT Val158Met polymorphism with risk of endometrial and ovarian cancer: a pooled analysis of case-control studies. AB - This meta-analysis was conducted to examine whether the genotype status of Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with endometrial and ovarian cancer risk. Eligible studies were identified by searching several databases for relevant reports published before January 1, 2014. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. In total, 15 studies (1,293 cases and 2,647 controls for ovarian cancer and 2,174 cases and 2,699 controls for endometrial cancer) were included in the present meta-analysis. When all studies were pooled into the meta analysis, there was no evidence for significant association between COMT Val158Met polymorphism and ovarian cancer risk (Val/Met versus Val/Val: OR=0.91, 95% CI=0.76-1.08; Met/Met versus Val/Val: OR=0.90, 95% CI=0.73-1.10; dominant model: OR=0.90, 95% CI=0.77-1.06; recessive model: OR=0.95, 95% CI=0.80-1.13). Similarly, no associations were found in all comparisons for endometrial cancer (Val/Met versus Val/Val: OR 0.97, 95% CI=0.77-1.21; Met/Met versus Val/Val: OR=1.02, 95% CI=0.73-1.42; dominant model: OR=0.98, 95% CI=0.77-1.25; recessive model: OR=1.02, 95% CI=0.87-1.20). In the subgroup analyses by source of control and ethnicity, no significant associations were found in any subgroup of population. This meta-analysis strongly suggests that COMT Val158Met polymorphism is not associated with increased endometrial and ovarian cancer risk. PMID- 25124597 TI - Pattern of tobacco use and its correlates among older adults in India. AB - PURPOSE: We examined tobacco use pattern and its correlates among older adults. MATERIALS AND METHODS: We used data of 9,852 older adults (>=60 years) (men 47% mean age 68 years) collected by the United Nations Population Fund on Ageing from seven Indian states. Logistic regression analysis was used to assess the correlates of tobacco use. RESULTS: Current use of any form of tobacco was reported by 27.8% (men 37.9%, women 18.8%); 9.2% reported only smoking tobacco, 16.9% smokeless tobacco only and 1.7% used both forms. Alcohol users (OR:5.20, 95% CI:4.06-6.66), men (OR:2.92, CI :2.71-3.47), those reporting lower income (OR:2.74, CI:2.16- 3.46), rural residents (OR 1.34, CI 1.17-1.54) and lower castes (OR:1.29, CI:1.13-1.47) were more likely to use any form of tobacco compared to their counterparts. CONCLUSIONS: Tobacco cessation interventions are warranted in this population focusing on alcohol users, men, those from lower income, rural residents and those belonging to a lower caste. PMID- 25124598 TI - The MMP-2 -735 C allele is a risk factor for susceptibility to breast cancer. AB - BACKGROUND: The expression of MMP genes has been demonstrated to be associated with tumor invasion, metastasis and survival rate for a variety of cancers. The functional promoter polymorphism MMP-2 C-735T is associated with decreased expression of the MMP-2 gene. The aim of present study was to detect any association between MMP-2 C-735T and susceptibility to breast cancer. MATERIALS AND METHODS: The MMP-2 C-735T polymorphism was studied in 233 women (98 with breast cancer and 135 healthy controls). All studied women were from Kermanshah and Ilam provinces of Western Iran. The MMP-2 C-735T polymorphism was detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) method. RESULTS: The frequencies of MMP-2 CC, CT and TT genotypes in healthy individuals were 59.3, 38.5 and 2.2%, respectively. However, in breast cancer patients, only CC (71.4%) and CT (28.6%) genotypes were observed (p=0.077). In patients the frequency of the MMP-2 C allele was significantly higher (85.7%) compared to that in controls (78.5 %, p=0.048). The presence of C allele of MMP-2 increased the risk of breast cancer by 1.64-fold [OR=1.64 (95%CI 1.01-2.7, p=0.049)]. The frequency of MMP-2 C allele was also higher in patients<=40 years (88.9%) than those aged >=41 years (67.5%, p=0.07). In addition, the frequency of MMP-2 C allele tended to be higher in patients with a family history of cancer in first-degree relatives (76.6%) compared to that without a family history of cancer (67.3%, p=0.31). CONCLUSIONS: Our findings indicate that the C allele of MMP-2 C-735T polymorphism is associated with increased risk of breast cancer. Also, the MMP-2 C allele might increase the risk of young onset breast cancer in our population. PMID- 25124599 TI - Iranian cancer patient perceptions of prognosis and the relationship to hope. AB - BACKGROUND: The aim of this study was to investigate Iranian cancer patient perceptions of their prognosis, factors that influence perceptions of prognosis and the effect this has on patient level of hope. MATERIALS AND METHODS: Iranian cancer patients (n=200) completed self-report measures of their perceptions of their prognosis and level of hope, in order to assess the relationship between the two and identify factors predictive of perceptions by multiple linear regression analysis. RESULTS: Cancer patients perceived of their prognosis positively (mean 11.4 out of 15), believed their disease to be curable, and reported high levels of hope (mean 40.4 out of 48.0). Multiple linear regression analyses demonstrated that participants who were younger, perceived they had greater family support, and had higher levels of hope reported more positive perceptions of their cancer prognosis. CONCLUSIONS: Positive perceptions of prognosis and its positive correlation with hope in Iranian cancer patients highlights the importance of cultural issues in the disclosure of cancer related information. PMID- 25124600 TI - Associations between AT-rich interactive domain 5B gene polymorphisms and risk of childhood acute lymphoblastic leukemia: a meta-analysis. AB - Previous genome-wide association studies (GWAS) have implicated several single nucleotide polymorphisms (SNPs) in the AT-rich interactive domain 5B (ARID5B) gene with childhood acute lymphoblastic leukemia (ALL). However, replicated studies reported some inconsistent results in different populations. Using meta analysis, we here aimed to clarify the nature of the genetic risks contributed by the two polymorphisms (rs10994982, rs7089424) for developing childhood ALL. Through searches of PubMed, EMBASE, and manually searching relevant references, a total of 14 articles with 16 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated to assess the associations. Both SNPs rs10994982 and rs7089424 showed significant associations with childhood ALL risk in all genetic models after Bonferroni correction. Furthermore, subtype analyses of B-lineage ALL provided strong evidence that SNP rs10994982 is highly associated with the risk of developing B-hyperdiploid ALL. These results indicate that SNPs rs10994982 and rs7089424 are indeed significantly associated with increased risk of childhood ALL. PMID- 25124601 TI - Anti-metastasis activity of black rice anthocyanins against breast cancer: analyses using an ErbB2 positive breast cancer cell line and tumoral xenograft model. AB - BACKGROUND: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. MATERIALS AND METHODS: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. RESULTS: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). CONCLUSIONS: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules. PMID- 25124602 TI - Novel DOX-MTX nanoparticles improve oral SCC clinical outcome by down regulation of lymph dissemination factor VEGF-C expression in vivo: oral and IV modalities. AB - BACKGROUND: Oral squamous cell carcinoma (OSCC) remains as one of the most difficult malignancies to control because of its high propensity for local invasion and cervical lymph node dissemination. The aim of present study was to evaluate the efficacy of novel pH and temperature sensitive doxorubicin methotrexate- loaded nanoparticles (DOX-MTX NP) in terms of their potential to change the VEGF-C expression profile in a rat OSCC model. MATERIALS AND METHODS: 120 male rats were divided into 8 groups of 15 animals administrated with 4 nitroquinoline-1-oxide to induce OSCCs. Newly formulated doxorubicin-methotrexate loaded nanoparticles (DOX-MTX NP) and free doxorubicin were IV and orally administered. RESULTS: RESULTS indicated that both oral and IV forms of DOX-MTX- nanoparticle complexes caused significant decrease in the mRNA level of VEGF-C compared to untreated cancerous rats (p<0.05) . Surprisingly, the VEGF-C mRNA was not affected by free DOX in both IV and oral modalities (p>0.05). Furthermore, in DOX-MTX NP treated group, less tumors characterized with advanced stage and VEGF C mRNA level paralleled with improved clinical outcome (p<0.05). In addition, compared to untreated healthy rats , the VEGF-C expression was not affected in healthy groups that were treated with IV and oral dosages of nanodrug (p>0.05). CONCLUSIONS: VEGF-C is one of the main prognosticators for lymph node metastasis in OSCC. Down-regulation of this lymph-angiogenesis promoting factor is a new feature acquired in group treated with dual action DOX-MTX-NPs. Beside the synergic apoptotic properties of concomitant use of DOX and MTX on OSCC, DOX-MTX NPs possessed anti-angiogenesis properties which was related to the improved clinical outcome in treated rats. Taking together, we conclude that our multifunctional doxorubicin-methotrexate complex exerts specific potent apoptotic and anti-angiogenesis properties that could ameliorate the clinical outcome presumably via down-regulating dissemination factor-VEGF-C expression in a rat OSCC model. PMID- 25124603 TI - Roles for paraoxonase but not ceruloplasmin in peritoneal washing fluid in differential diagnosis of gynecologic pathologies. AB - BACKGROUND: Intraperitoneal spread of gynecologic cancers is a major cause of mortality and morbidity and often presents with malignant ascites. Microscopic tumor spread can be demonstrated by a peritoneal wash cytology and help assess the prognosis of the disease. In our study, the roles of paraoxonase and ceruloplasmin, measured in peritoneal washing fluid of patients operated for gynecologic pathologies in differential diagnosis was investigated. MATERIALS AND METHODS: Patients operated for malign or benign gynecologic pathologies in Antalya Education and Research Hospital Gynecology Clinic between 2010-2012 were included in the study. Samples were obtained during surgery. RESULTS: A statistically significant difference was detected between patients with benign and malign diseases with regards to PON1 levels measured in peritoneal washing fluid (p:0.044), the average values being 64.2+/-30.8 (Range 10.8-187.2) and 41.4+/-21.4 (Range 10.4-95.5), respectively. No significant variation was evident for ceruloplasmin. CONCLUSIONS: Paraoxonase levels measured in peritoneal washing fluid may contribute to the differentiation of malign-benign diseases in gynecologic pathologies. PMID- 25124604 TI - Comparison of neutrophil/lymphocyte and platelet/ lymphocyte ratios for predicting malignant potential of suspicious ovarian masses in gynecology practice. AB - PURPOSE: To compare the diagnostic accuracy of the neutrophil/lymphocyte ratio (NLR) with the platelet/lymphocyte ratio (PLR) in predicting malignancy of pelvic masses which are pre-operatively malignant suspicious. MATERIALS AND METHODS: In this retrospective study we evaluated the clinical features of patients with ovarian masses which had pre-operatively been considered suspicious for malignancy. The patients whose intraoperative frozen sections were malign were classified as the study group, while those who had benign masses were the control group. Data recorded were age of the patient, diameter of the mass, pre-operative serum Ca 125 levels, platelet count, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio. RESULTS: There was statistically significantly difference between the groups in terms of age, diameter of the mass, serum Ca 125 levels, platelet number and platelet/lymphocyte ratio. Mean neutrophil/lymphocyte ratios showed no difference between the groups. ROC curve analysis showed that age, serum Ca 125 levels, platelet number and PLR were discriminative markers in predicting malignancy in adnexal masses. CONCLUSIONS: According to the current study, serum Ca 125 levels, pre-operative platelet number and PLR may be good prognostic factors, while NLR is an ineffective marker in predicting the malignant characteristics of a pelvic mass. PMID- 25124605 TI - miRNA-1297 induces cell proliferation by targeting phosphatase and tensin homolog in testicular germ cell tumor cells. AB - To investigate the role of miR-1297 and the tumor suppressor gene PTEN in cell proliferation of testicular germ cell tumors (TGCT). MTT assays were used to test the effect of miR-1297 on proliferation of the NCCIT testicular germ cell tumor cell line. In NCCIT cells, the expression of PTEN was assessed by Western blotting further. In order to confirm target association between miR-1297 and 3' UTR of PTEN, a luciferase reporter activity assay was employed. Moreover, roles of PTEN in proliferation of NCCIT cells were evaluated by transfection of PTEN siRNA. Proliferation of NCCIT cells was promoted by miR-1297 in a concentration dependent manner. In addition, miR-1297 could bind to the 3'-UTR of PTEN based on luciferase reporter activity assay, and reduced expression of PTEN at protein level was found. Proliferation of NCCIT cells was significantly enhanced after knockdown of PTEN by siRNA. miR-1297 as a potential oncogene could induce cell proliferation by targeting PTEN in NCCIT cells. PMID- 25124606 TI - Emodin inhibits breast cancer cell proliferation through the ERalpha-MAPK/Akt cyclin D1/Bcl-2 signaling pathway. AB - BACKGROUND: The aim of the present study was to investigate the involvement of emodin on the growth of human breast cancer MCF-7 and MDA-MB-231 cells and the estrogen (E2) signal pathway in vitro. MATERIALS AND METHODS: MTT assays were used to detect the effects of emodin on E2 induced proliferation of MCF-7 and MDA MB-231 cells. Flow cytometry (FCM) was applied to determine the effect of emodin on E2-induced apoptosis of MCF-7 cells. Western blotting allowed detection of the effects of emodin on the expression of estrogen receptor alpha, cyclin D1 and B cell lymphoma-2 (Bcl-2), mitogen-activated protein kinases (MAPK) and phosphatidylinostiol 3-kinases (PI3K). Luciferase assays were emplyed to assess transcriptional activity of ERalpha. RESULTS: Emodin could inhibit E2-induced MCF 7 cell proliferation and anti-apoptosis effects, and arrest the cell cycle in G0/G1 phase, further blocking the effect of E2 on expression and transcriptional activity of ERalpha. Moreover, Emodin influenced the ER alpha genomic pathway via downregulation of cyclin D1 and Bcl-2 protein expression, and influenced the non genomic pathway via decreased PI3K/Akt protein expression. CONCLUSIONS: These findings indicate that emodin exerts inhibitory effects on MCF-7 cell proliferation via inhibiting both non-genomic and genomic pathways. PMID- 25124607 TI - Survival of colorectal cancer patients in the presence of competing-risk. AB - BACKGROUND: Colorectal cancer (CRC) is considered to be a main cause of malignancy-related death in the world, being commonly diagnosed in both men and women. It is the third leading cause of cancer dependent death in the world and there are one million new cases diagnosed per year. In Iran the incidence of colorectal cancer has increased during the last 25 years and it is the fifth cause of cancer in men and the third in women. MATERIALS AND METHODS: In this article we analyzed the survival of 475 colorectal patients of Taleghani hospital in Tehran with the semi-parametric competing-risks model. RESULTS: There were 55% male cases and at the time of the diagnosis most of the patients were between 48 and 67 years old. The probability of a patient death from colorectal cancer with survival of more than 25 years was about 0.4. Body mass index, height, tumour site and gender had no influence. CONCLUSIONS: According to these data and by using semi-parametric competing-risks method, we found out that only age at diagnosis has a significant effect on these patient survival time. PMID- 25124608 TI - Development of in-house multiplex real time PCR for human papillomavirus genotyping in Iranian women with cervical cancer and cervical intraepithelial neoplasia. AB - BACKGROUND: HPV related cervical cancer as one of the most common women cancers in developing countries. Regarding accessibility of commercial vaccines, any long or short term modality for integrating preventive immunization against HPV in a national program needs comprehensive information about HPV prevalence and its genotypes. The important role of selecting most accurate diagnostic technologies for obtaining relevant data is underlined by different assays proposed in the literature. The main objective of the present study was to introduce an in-house HPV typing assay using multiplex real time PCR with reliable results and affordable cost for molecular epidemiology surveys and diagnosis. MATERIALS AND METHODS: 112 samples of formalin fixed paraffin embedded tissues and liquid based cytology specimens from patients with known different grades of cervical dysplasia and invasive cancer, were examined by this method and the result were verified by WHO HPV LabNet proficiency program in 2013. RESULTS: HPV was detected in 105 (93.7%) out of 112 samples. The dominant types were HPV 18 (61.6%) and HPV 16 (42.9%). Among the mixed genotypes, HPV 16 and 18 in combination were seen in 12.4% of specimens. CONCLUSIONS: According to acceptable performance, easy access to primers, probes and other consumables, affordable cost per test, this method can be used as a diagnostic assay in molecular laboratories and for further planning of cervical carcinoma prevention programs. PMID- 25124609 TI - Timing of thoracic radiotherapy in limited stage small cell lung cancer: results of early versus late irradiation from a single institution in Turkey. AB - BACKGROUND: It is standard treatment to combine chemotherapy (CT) and thoracic radiotherapy (TRT) in treating patients with limited stage small cell lung cancer (LS-SCLC). However, optimal timing of TRT is unclear. We here evaluated the survival impact of early versus late TRT in patients with LS-SCLC. MATERIALS AND METHODS: Follow-up was retrospectively analyzed for seventy consecutive LS-SCLC patients who had successfully completed chemo-TRT between January 2006 and January 2012. Patients received TRT after either 1 to 2 cycles of CT (early TRT) or after 3 to 6 cycles of CT (late TRT). Survival and response rates were evaluated using the Kaplan-Meier method and comparisons were made using the multivariate Cox regression test. RESULTS: Median follow-up was 24 (5 to 57) months. Carboplatin+etoposide was the most frequent induction CT (59%). Median overall, disease free, and metastasis free survivals in all patients were 15 (5 to 57), 5 (0 to 48) and 11 (3 to 57) months respectively. Late TRT was superior to early TRT group in terms of response rate (p=0.05). 3 year overall survival (OS) rates in late versus early TRT groups were 31% versus 17%, respectively (p=0.03). Early TRT (p=0.03), and incomplete response to TRT (p=0.004) were negative predictors of OS. Significant positive prognostic factors for distant metastasis free survival were late TRT (p=0.03), and use of PCI (p=0.01). Use of carboplatin versus cisplatin for induction CT had no significant impact on OS (p=0.634), DFS (p=0.727), and MFS (p=0.309). CONCLUSIONS: Late TRT appeared to be superior to early TRT in LS-SCLC treatment in terms of complete response, OS and DMFS. Carboplatin or cisplatin can be combined with etoposide in the induction CT owing to similar survival outcomes. PMID- 25124610 TI - MiR-150-5p suppresses colorectal cancer cell migration and invasion through targeting MUC4. AB - Growing evidence suggests that miR-150-5p has an important role in regulating genesis of various types of cancer. However, the roles and the underlying mechanisms of miR-150-5p in development of colorectal cancer (CRC) remain largely unknown. Transwell chambers were used to analyze effects on cell migration and invasion by miR-150-5p. Quantitative real-time PCR (qRT-PCR), Western blotting and dual-luciferase 3' UTR reporter assay were carried out to identify the target genes of miR-150-5p. In our research, miR-150-5p suppressed CRC cell migration and invasion, and MUC4 was identified as a direct target gene. Its effects were partly blocked by re-expression of MUC4. In conclusiomn, miR-150-5p may suppress CRC metastasis through directly targeting MUC4, highlighting its potential as a novel agent for the treatment of CRC metastasis. PMID- 25124611 TI - Efficacy and tolerance of pegaspargase-based chemotherapy in patients with nasal type extranodal NK/T-cell lymphoma: a pilot study. AB - Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received 2500 IU/m2/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal type ENKL. PMID- 25124612 TI - Identification of patients with microscopic hematuria who are at greater risk for the presence of bladder tumors using a dedicated questionnaire and point of care urine test--a study by the members of Association of Urooncology, Turkey. AB - In patients with microscopic hematuria there is a need for better identification of those who are at greater risk of harbouring bladder tumors. The RisikoCheck(r) questionnaire has a strong correlation with the presence of urothelial carcinoma (UC) of the bladder and in combination with other available tests may help identify patients who require detailed clinical investigations due to increased risk of presence of bladder tumors. This study aimed to evaluate the efficacy of RisikoCheck(r) questionnaire together with NMP-22(r) (BladderChek(r)) as a point of-care urine test in predicting the presence of bladder tumors in patients presenting with microscopic hematuria as the sole finding. In this multi institutional prospective evaluation of 303 consecutive patients without a history of urothelial carcinoma (UC), RisikoCheck(r) risk group assessment, urinary tract imaging and cystourethroscopy as well as urine cytology and Nuclear Matrix Protein-22 (NMP-22 BladderChek) testing were performed where available. The sensitivity, specificity, negative predictive value (NPV), and positive predictive values (PPV) for the risk adapted approach were calculated. All patients underwent cystoscopy, and tumors were detected in 18 (5.9%). Urine cytology and NMP-22 was positive for malignancy in 9 (3.2%) and 12 (7.5%) of patients, respectively. A total of 43 (14%) patients were in the high risk group according to the RisikoCheck(r) questionnaire. The sensitivity and specificity of the questionnaire in detecting a bladder tumor was 61.5 % and 84.0 % in the high risk group. In patients with either a positive NMP-22 test or high risk category RisikoCheck(r), 23.6% had bladder tumors with a corresponding sensitivity of 54.2% and specificity of 88.6%. If both tests were negative only 3.3% of the patients had bladder tumors. The results of our study suggest that the efficacy of diagnostic evaluation of patients with microscopic hematuria may be further enhanced by combining RisikoCheck(r) questionnaire with NMP-22. PMID- 25124613 TI - Effect of lymphangiogenesis and lymphovascular invasion on the survival pattern of breast cancer patients. AB - BACKGROUND: Invasion of breast cancer cells into blood and lymphatic vessels is one of the most important steps for metastasis. In this study the prognostic relevance of lymphangiogenesis and lymphovascular invasion (LVI) in breast cancer patients was evaluated in terms of survival. MATERIALS AND METHODS: This retrospective study concerned 518 breast cancer patients who were treated at Department of Surgical Oncology, Saroj Gupta Cancer Centre and Research Institute, Kolkata-700063, West Bengal, India, a reputed cancer centre and research institute of eastern India between January 2006 and December 2007. RESULTS: The median overall survival and disease free survival of the patients were 60 months and 54 months respectively. As per Log-rank test, poor overall as well as disease free survival pattern was observed for LVI positive patients as compared with LVI negative patients (p<0.01). Also poor overall as well as disease free survival pattern was observed for perineural invasion (PNI) positive patients as compared to PNI negative patients (p<0.01). CONCLUSIONS: From this study it is evident that LVI and PNI are strongly associated with outcome in terms of disease free as well as overall survival in breast cancer patients. Thus LVI and PNI constitute potential targets for treatment of breast cancer patients. We advocate incorporating their status into breast cancer staging systems. PMID- 25124614 TI - Combined detection of CEA, CA 19-9, CA 242 and CA 50 in the diagnosis and prognosis of resectable gastric cancer. AB - Our aim was to investigate the value of combined detection of serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 242 and CA 50 in diagnosis and assessment of prognosis in consecutive gastric cancer patients. Clinical data including preoperative serum CEA, CA 19-9, CA 242, and CA 50 values and information on clinical pathological factors were collected and analyzed retrospectively. Univariate and multivariate survival analyses were used to explore the relationship between tumor markers and survival. Positive rates of tumor markers CEA, CA 19-9, CA 242 and CA 50 in the diagnosis of gastric cancer were 17.7, 17.1, 20.4 and 13.8%, respectively, and the positive rate for all four markers combined was 36.6%. Patients with elevated preoperative serum concentrations of CEA, CA 19-9, CA 242 and CA 50, had late clinical tumor stage and significantly poorer overall survival. Five-year survival rates in patients with elevated CEA, CA 19-9, CA 242 and CA 50 were 28.1, 25.8, 27.0 and 24.1%, respectively, compared with 55.0, 55.4, 56.4 and 54.5% in patients with these markers at normal levels (p<0.01). In multivariate Cox proportional hazards analyses, an elevated CA 242 level was determined to be an independent prognostic marker in gastric cancer patients. Combined detection of four tumor markers increased the positive rate for gastric cancer diagnosis. CA 242 showed higher diagnostic value and CA 50 showed lower diagnostic value. In resectable gastric carcinoma, preoperative CA 242 level was associated with disease stage, and was found to be a significant independent prognostic marker in gastric cancer patients. PMID- 25124615 TI - Preliminary evaluation of the in vitro efficacy of 1, 2-di (quinazolin-4-yl) diselane against SiHa cervical cancer cells. AB - Cervical cancer is one the most common malignancies among females. In recent years, its incidence rate has shown a rising trend in some countries so that development of anticancer drugs for cervical cancer is an urgent priority. In our recent anticancer drug discovery screen, 1, 2-di (quinazolin-4-yl)diselane (LG003) was found to possess wide spectrum anticancer efficacy. In the present work, the in vitro anticancer activity of LG003 was evaluated in the SiHa cervical cancer cell line. Compared with commercial anticancer drugs 10 hydroxycamptothecin, epirubicin hydrochloride, taxol and oxaliplatin, LG003 showed better anticancer activity. Furthermore, inhibition effects were time- and dose-dependent. Morphological observation exhibited LG003 treatment results in apoptosis like shrinking and blebbing, and cell membrane damage. Lactate dehydrogenase release assay revealed that LG003 exerts such effects in SiHa cells through a physiology pathway rather than cytotoxicity, which suggests that title compound LG003 can be a potential candidate agent for cervical cancer. PMID- 25124616 TI - Are women in Kuwait aware of breast cancer and its diagnostic procedures? AB - The aim of this study was to examine the knowledge and awareness of women in Kuwait with regard to risk factors, symptoms and diagnostic procedures of breast cancer. A total of 521 questionnaires were distributed among women in Kuwait. Results showed that 72% of respondents linked breast cancer factors to family history, while 69.7% scored abnormal breast enlargement as the most detectable symptom of the disease. Some 84% of participants had heard about self examination, but knowledge about mammograms was limited to 48.6% and only 22.2% were familiar with diagnostic procedures. Some 22.9% of respondents identified the age over 40 years as the reasonable age to start mammogram screening. Risk factor awareness was independent on age groups (p>0.05), but both high education and family history increased the likelihood of postivie answers; the majority knew about a few factors such as aging, pregnancy after age 30, breast feeding for short time, menopause after age of 50, early puberty, and poor personal hygiene. In conclusion, 43.1% of participants had an overall good knowledge of breast cancer with regards to symptoms, risk factors and breast examination. Very highly significant associations (p<0.005) were evident for all groups except for respondents distributed by nationality (p=0.444). Early campaigns for screening the breast should be recommended to eliminate the confusion of wrong perceptions about malignant mammary disease. PMID- 25124617 TI - Expression of neuronal markers, NFP and GFAP, in malignant astrocytoma. AB - BACKGROUND: Immunohistochemical markers are considered as important factors in diagnosis of malignant astrocytomas. The aim of the current study was to investigate the frequency of the immunohistochemical markers neurofilament protein (NFP) and glial fibrillary acidic protein (GFAP) in malignant astrocytoma tumors in Firoozgar and Rasool-Akram hospitals from 2005 to 2010. MATERIALS AND METHODS: In this cross-sectional study, immunohistochemical analysis of NFP and GFAP was performed on 79 tissue samples of patients with the diagnosis of anaplastic and glioblastoma multiform (GBM) astrocytomas. RESULTS: The obtained results demonstrated that all patients were positive for GFAP and only 3.8% were positive for NFP. There was no significant association between these markers and clinical, demographic, and prognostic features of patients (p>0.05). CONCLUSIONS: NFP was expressed only in GBMs and not in anaplastic astrocytomas. It would be crucial to confirm the present findings in a larger number of tumors, especially in high grade gliomas. PMID- 25124618 TI - Activation of JNK/p38 pathway is responsible for alpha-methyl-n-butylshikonin induced mitochondria-dependent apoptosis in SW620 human colorectal cancer cells. AB - alpha-Methyl-n-butylshikonin (MBS), one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we assess the molecular mechanisms of MBS in causing apoptosis of SW620 cells. MBS reduced the cell viability of SW620 cells in a dose-and time-dependent manner and induced cell apoptosis. Treatment of SW620 cells with MBS down-regulated the expression of Bcl-2 and up-regulated the expression of Bak and caused the loss of mitochondrial membrane potential. Additionally, MBS treatment led to activation of caspase-9, caspase-8 and caspase-3, and cleavage of PARP, which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. MBS also induced significant elevation in the phosphorylation of JNK and p38. Pretreatment of SW620 cells with specific inhibitors of JNK (SP600125) and p38 (SB203580) abrogated MBS-induced apoptosis. Our results demonstrated that MBS inhibited growth of colorectal cancer SW620 cells by inducing JNK and p38 signaling pathway, and provided a clue for preclinical and clinical evaluation of MBS for colorectal cancer therapy. PMID- 25124619 TI - Patterns and trends with cancer incidence and mortality rates reported by the China National Cancer Registry. AB - National cancer registration reports provide a huge potential for identifying patterns and trends of important policy, research, prevention and treatment significance. As summary reports written on an annual basis, the China Cancer Registry Annual Reports (CCRARs) fall short from fully addressing their potential. This paper attempts to explore part of the patterns and trends hidden behind published CCRARs. It extracted data for cancer incidence rates (IRs) and mortality rates (MRs) for 2004, 2006 and 2009 from relevant CCRARs and portrayed 4 kinds of indicators in line graphs. The study showed that: a) all of the line graphs of age-specific IRs and MRs characterized typical "growth curves or histogram"; b) graphs of IRs and MRs for males and urban areas had higher peaks than that for females and rural regions; c) most of the line graphs of IR/MR ratios comprised a starting peak, a secondary peak and a decreasing tail and the secondary peaks for females and urban areas were higher than those for males and rural areas; d) most of the urban versus rural IR ratios valued above one, but most the urban versus rural MR ratios, below one; e) the accumulative IRs and MRs showed a stable increasing trend from 2004 to 2009 for urban areas, but mixed for rural regions. PMID- 25124620 TI - Lack of association between the MTHFRC677T polymorphism and lung cancer in a Turkish population. AB - BACKGROUND: In this case-control study, we aimed to investigate the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and lung cancer. MATERIALS AND METHODS: Total 200 individuals including 100 patients with lung cancer and 100 controls were analyzed. Genotyping of MTHFR C677T was performed using PCR and RFLP methods. RESULTS: The majority of the patients were men and 90% were smokers. We found that the risk ratio for development of LC was 13-times higher in smokers compared with non-smokers between patient and control groups in our study (OR:13.5, 95%CI:6.27-29.04, p:0.0001). Besides, the risk ratio for development of LC was nine times higher in individuals with cancer history in their family than those without cancer history (OR:9.65, 95%CI: 2.79 33.36; p:0.0001). When genotype distributions and allele frequencies were analyzed in the study groups, no significant difference was apparent (chi2:0.53, p=0.76). In addition, no correlation between genotypes of MTHFRC677T polymorphism and histological type of LC was found (chi2:0.99, p=0.60). CONCLUSIONS: These results suggest that there was no association between the MTHFR C677T polymorphism and lung cancer in the Turkish population. PMID- 25124621 TI - Outcome of rectal cancer in patients aged 30 years or less in the Pakistani population. AB - BACKGROUND: The incidence of rectal cancer is increasing in younger age groups. Limited data is available regarding survival outcome in younger patients with conflicting results from western world. The goal of this study was to determine survival in patients with rectal cancer<30 years of age and compare it with their older counterparts in the Pakistani population. MATERIALS AND METHODS: A retrospective chart review of patients operated for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided into two groups, Group 1 aged <=30 years and Group 2 aged >30 years. Patient characteristics, surgical procedure, histopathological details and number of loco regional and distant failures were compared. Expected 5 year survival was calculated using Kaplan Meier curves and significance was determined using the Log rank test. RESULTS: There were 38 patients in group 1 and 144 in group 2. A significantly high number of younger patients presented with poorly differentiated histology (44.7% vs 9.7%) (p=0.0001) and advanced pathological stage (63.1% vs 38.1%) (p=0.04). Predicted overall 5 year survival was 38% versus 57% in groups I and II, respectively (p=0.05). Disease free survival was 37% versus 52% and was significantly different (p=0.007). CONCLUSIONS: Early onset rectal cancer is associated with poor pathological features and a worse outcome in Pakistani population. PMID- 25124622 TI - Preparation and antitumor activity of a tamibarotene-furoxan derivative. AB - Multi-target drug design, in which drugs are designed as single molecules to simultaneously modulate multiple physiological targets, is an important strategy in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was here prepared and proposed to exert synergistic effects on antileukemia by releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT 011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was more effective evaluated in a nude mice U937 xenograft model in vivo. In addition, QT-011 could release nitric oxide which might contribute to the antiproliferative activity. Autodocking assays showed that QT-011 fits well with the hydrophobic pocket of retinoic acid receptors. Taken together, these results suggest that QT-011 might be a highly effective derivative of tamibarotene and a potential candidate compound as antileukemia agent. PMID- 25124623 TI - Insulin promotes proliferation and migration of breast cancer cells through the extracellular regulated kinase pathway. AB - The present study was undertaken to determine the roles of insulin in the growth of transplanted breast cancer in nude mice, and the proliferation and migration of MCF-7 human breast cancer cells and assess its influence on downstream signaling pathways. In a xenograft mouse model with injection of MCF-7 human breast cancer cells, tumor size was measured every other day. The insulin level and insulin receptor (IR) were increased in the breast cancer patient tissues. Insulin injected subcutaneously around the tumor site in mice caused increase in the size and weight of tumor masses, and promoted proliferation and migration of MCF-7 cells. The effects of insulin on the increase in the proliferation and migration of MCF-7 human breast cancer cells were abolished by pretreatment with the extracellular regulated kinase (ERK) inhibitor PD98059. Insulin increased the phosphorylation of ERK in the MCF-7 cells. These results indicate that insulin promotes the growth of breast cancer in nude mice, and increases the proliferation and migration of MCF-7 human breast cancer cells via the ERK pathway. PMID- 25124624 TI - Risk factors of lymph node metastases with endometrial carcinoma. AB - BACKGROUND: The purpose of this study was to investigate and evaluate risk factors for lymph node metastases (LNM) in cases of endometrial cancer (EC). MATERIALS AND METHODS: A retrospective single institution analysis of patients surgically staged for EC at Ankara Oncology Education and Research Hospital from 1996 to 2010 was performed. Roles of prognostic factors, such as age, histological type, grade, depth of myometrial invasion, cervical involvement, peritoneal cytology, and tumor size, in the prediction of LNM were evaluated. Fisher's exact test and logistic regression analysis were used to assess the effects of various factors on LNM. RESULTS: LNM was observed in 22 out of 247 patients (8.9%) and was significantly more common in the presence of tumors of higher grade, deep myometrial invasion (DMI), cervical involvement, size>2 cm, and with positive peritoneal cytology. Logistic regression analysis revealed that DMI remained the only independent risk factor for LNM. NPV, PPV, sensitivity, and specificity for satisfying LNM risk were 98.0, 19.5, 86.3, and 65.3%, respectively for DMI. CONCLUSIONS: The incidence of LNM is influenced independently by DMI. If data support a conclusion of DMI, LND should be seriously considered. PMID- 25124625 TI - Cancers of the young population in Brunei Darussalam. AB - BACKGROUND: Globally, the overall incidence of cancer is increasing as a result of ageing populations and changing lifestyles. Cancer is one of the leading causes of death, especially in the developed nations. Cancers affecting the young population are generally considered uncommon. This study assessed the demography and trends of cancers of the young in Brunei Darussalam, a small and developing Southeast Asia nation. MATERIALS AND METHODS: All patients diagnosed with cancers between 2000 and 2012 were identified from the cancer registry maintained by the State Histopathology Laboratory. Cancers of the young was defined as any cancers diagnosed under the age of 40 years. Demographic data and the type of cancers were collected and analysed using SPSS Statistics 17.0. RESULTS: Among the 6,460 patients diagnosed with cancer over the study period, 18.7% (n=1,205) were categorized as young with an overall decline in the proportion from 26.6% in 2000 to 18.8% in 2012 (p<0.001 for trend). Among all cancers of the young, the most common systems affected were gynecological (24.1%), hematological/lymphatic (15.8%), subcutaneous/dermatological/ musculoskeletal (10.5%), breast (10.5%) and gastrointestinal (9.9%). Overall, among the different systems, neurological (54.9%) had the highest proportion of cancers of the young followed by gynecological/reproductive (30.6%), hematological/ lymphatic (39.9%), endocrine (38.7%), subcutaneous/dermatological/ musculoskeletal (22.3%) and the head and neck region (20.1%). There was a female predominance (66.9%) and the incidence was significantly higher among the Malays (20.1%) and expatriates (25.1%) groups compared to the Chinese (10.7%) and indigenous (16.8%) groups (p<0.001 for trend). CONCLUSIONS: Cancers of the young (<40 years) accounted for almost a fifth of all cancers in Brunei Darussalam with certain organ systems more strongly affected. There was a female preponderance in all racial groups. Over the years, there has been a decline in the overall proportion of cancers of the young. Selective screening programs should nevertheless be considered. PMID- 25124626 TI - Preventive effect of Actinidia valvata Dunn extract on N-methyl-N'-nitro-N nitrosoguanidine-induced gastrointestinal cancer in rats. AB - PURPOSE: This study was conducted to assess the preventive effect of Actinidia valvata Dunn (AVD) extract on an animal model of gastrointestinal carcinogenesis on the basis of changes in tumor incidence, cell proliferation, and apoptosis. MATERIALS AND METHODS: Seventy-five male Wistar rats were divided into five different treatment groups with 15 rats in each group. Group I was given normal feed, whereas Groups II to IV were treated with 10% sodium chloride in the first six weeks and 100 ug/mL of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 24 weeks. Group II was then given normal feed, whereas Group III was given AVD extract (0.24 g/kg/day) for 12 weeks. Group IV was given AVD extract from the first week to the 36th week, whereas Group V was treated with AVD extract alone for 36 weeks. All rats were sacrificed at the end of the 36 week experiment and assessed for the presence of gastrointestinal tumors. The occurrence of cancer was evaluated by histology. Bax, Bcl-2, Caspase-3, and cyclinD1 were determined by immunohistochemical staining and Western blotting. RESULTS: The incidences of gastric cancer were 0% in Group I, 73.3% in Group II, 33.3% in Group III, 26.7% in Group IV, and 0% in Group V. Bcl-2 and cyclinD1 expression was decreased in AVD extract treated groups, whereas Bax and Caspase-3 expression was increased. Comparison with group II revealed significant differences (p<0.01). CONCLUSIONS: AVD extract exhibits an obvious preventive effect on gastrointestinal carcinogenesis induced by MNNG in rats through the regulation of cell proliferation and apoptosis. PMID- 25124627 TI - Circulating tumor cells are associated with bone metastasis of lung cancer. AB - Lung cancer (LC) is the leading cause of cancer mortality worldwide, predominantly due to the difficulty of early diagnosis and its high metastatic potential. Recently, increasing evidence suggests that circulating tumour cells (CTCs) are responsible for cancer metastatic relapse, and CTCs have attracted interest in cancer metastasis detection and quantification. In present study, we collected blood samples from 67 patients with bone metastasis, and 30 patients without such metastasis, and searched for CTCs. Then the association of CTC numbers with bone metastasis and other clinico-pothological variants was analyzed. Results demonstrated that when 5 or 1 was taken as a threshhold for the CTC number, there were significantly higher positivity of CTCs in the bone metastasis group than in the non-metastasis group. While the increase in CTC number was not significantly associated with any other clinicopathological factor, including age, gender, pathological type, intrapulmonary metastasis and lymph node metastasis, the CTC number in patients with positivity of the last above mentioned variants was obviously higher than in patients with negativity of the two variants. Taken together, the CTC number appears to be significantly associated with the bone metastasis from lung cancer. PMID- 25124629 TI - Descriptive report on pattern of variation in cancer cases within selected ethnic groups in Kamrup Urban District of Assam, 2009-2011. AB - BACKGROUND: The global burden of cancer is continuously increasing. According to recent report of the National Cancer Registry Programme (NCRP) on time trends it is estimated that future burden of cancer cases for India in 2020 will be 1,320,928. It is well known that knowledge of the incidence of cancer is a fundamental requirement of rational planning and monitoring of cancer control programs. It would help health planners to formulate public health policy if relevant ethnic groups were considered. North East-India alone contains over 160 Scheduled Tribes and 400 other sub-tribal communities and groups, whose cancer incidence rates are high compared to mainland India. As since no previous study was done focusing on ethnicity, the present investigation was performed. MATERIALS AND METHODS: In this paper PBCR-Guwahati data on all cancer registrations from January 2009 to December 2011 for residents of the Kamrup Urban District, comprising an area of 261.8 sq. km with a total population of 900,518, including individual records with information on sex, age, ethnicity and cancer site are provided. Descriptive statistics including age adjusted rates (AARs) were taken as provided by NCRP. For comparison of proportional incidence ratios (PIR) the Student's t test was used, with p<0.05 considered as statistically significant. RESULTS AND CONCLUSIONS: Differences in leading sites of Kamrup Urban District since from the beginning of the PBCR-Guwahati were revealed among different ethnic groups by this study. The results should help policy makers to formulate different strategies to control the level of burden as well as for treatment planning. This study also suggests that age is an important factor of cancer among different ethnic populations as well as for overall population of Kamrup District of Assam. PMID- 25124628 TI - Is the neutrophil-lymphocyte ratio an indicator of progression in patients with benign prostatic hyperplasia? AB - PURPOSE: The aim of this study was to evaluate inflammation parameters and assess the utility of the neutrophil- lymphocyte ratio (NLR) as a simple and readily available predictor for clinical disease activity in patients with nenign prostate hyperplasia BPH. We also aimed to investigate the relationship between inflammatory parameters with alpha-blocker therapy response, and evaluate the potential association between NLR and the progression of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We examined 320 consecutive patients (July 2013-December 2013) admitted to our outpatient clinic with symptoms of the lower urinary tract at Bozok University. The mean age was 60 (range, 51-75) years. Complete blood count (CBC), prostate-specific antigen (PSA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were assessed. Correlations between PSA, CRP, ESR, prostate volume, International Prostate Symptom Score (IPPS), maximum urinary flow rate (Qmax), and NLR were assessed statistically. Patients were divided into two groups: high and low risk of progression. RESULTS: NLR was positively correlated with IPSS (p=0.001, r=0.265), PSA (p=0.001, r=0.194), and negatively correlated with Qmax (p<0.001, r=-0.236). High-risk patients a had a higher NLR compared with low-risk patients, based on IPSS (p<0.001), PSA (p=0.013), and Qmax (p<0.001); however, there were no significant differences between the groups in terms of age (p>0.05), and prostate volume (p>0.05). CONCLUSIONS: NLR can predict BPH progression. We propose that increased inflammation is negatively associated with clinical status in BPH patients and suggest that NLR can give information along with LUTS severity which may be used as a readikly accessible marker for patient follow-up. PMID- 25124630 TI - Prognostic significance of the peripheral blood absolute monocyte count in patients with locally advanced or metastatic hepatocellular carcinoma receiving systemic chemotherapy. AB - BACKGROUND: The prognostic significance of the circulating absolute monocyte count (AMC) in patients with locally advanced hepatocellular carcinoma (HCC) is uncertain. This study was designed to assess the association of circulating AMC with survival outcomes in patients diagnosed with locally advanced or metastatic HCC receiving systemic chemotherapy. MATERIALS AND METHODS: Between January 1, 2005 and December 30, 2012, locally advanced or metastatic HCC patients who had Child-Pugh stage A or B disease and received systemic chemotherapy were retrospectively enrolled. Patient features including gender, age, extrahepatic metastasis, Child-Pugh stage, serum alpha-fetoprotein(AFP) level and AMC were collected to investigate their prognostic impact on overall survival(OS). RESULTS: A total of 216 patients were eligible for the study. The optimal cut-off value of AMC for OS analysis was 0.38*109/L. Median OS was 5.84 months in low-AMC group (95% confidence interval [CI], 5.23 to 6.45), and 5.21 months in high-AMC group (95% CI, 4.37 to 6.04; p=0.003). In COX multivariate analysis, elevated AMC remained as an independent prognostic factor for worse OS (HR, 1.578; 95% CI, 1.120 to 2.223, p=0.009). CONCLUSIONS: Our results indiicate that circulating AMC is confirmed to be an independent prognostic factor for OS in patients with locally advanced or metastatic HCC receiving systemic chemotherapy. PMID- 25124631 TI - Aquaporin 8 involvement in human cervical cancer SiHa migration via the EGFR Erk1/2 pathway. AB - Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24 h and 48 h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48 h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway. PMID- 25124632 TI - Loss of expression and aberrant methylation of the CDH1 (E-cadherin) gene in breast cancer patients from Kashmir. AB - BACKGROUND: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. MATERIALS AND METHODS: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. RESULTS: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). CONCLUSIONS: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information. PMID- 25124633 TI - Prevalence of abnormal anal cytology in HIV-infected women: a hospital-based study. AB - BACKGROUND: To study the prevalence of abnormal anal cytology by Papanicolaou (Pap) technique in HIV- infected women who attended a HIV clinic at Prapokklao Hospital, Chanthaburi, Thailand. MATERIALS AND METHODS: HIV-infected women who attended a HIV clinic at Prapokklao Hospital from March 2013 to February 2014 were recruited for anal Pap smears. Participants who had abnormal results of equally or over "abnormal squamous/glandular cells of undetermined significance" (ASC-US) were classified as abnormal anal cytology. RESULTS: A total of 590 anal Pap smears were performed at HIV clinic of Prapokklao Hospital during the study period. There were only 13 patients who had abnormal Pap tests, which were: 11 ASC-US and 2 HSIL (high grade squamous intraepithelial lesion). The prevalence of abnormal anal Pap smears in HIV-infected women who attended HIV clinic at Prapokklao Hospital was 2.2 percent. Percentage of high risk HPV in patients who had abnormal Pap test was 88.9 (8/9). CONCLUSIONS: The prevalence of abnormal anal Papanicolaou smears in HIV-infected women who attended the HIV clinic at Prapokklao hospital was quite low in comparison to the earlier literature. PMID- 25124634 TI - Analysis of mammographic breast density in a group of screening chinese women and breast cancer patients. AB - BACKGROUND: A dense breast not only reduces the sensitivity of mammography but also is a moderate independent risk factor for breast cancer. The percentage of Western women with fat breast tissue is higher aged 40 years or older. To a certain extent, mammography as a first choice of screening imaging method for Western women of this group is reasonable. Hitherto, the frequency and age distribution of mammographic breast density patterns among Chinese women had not been characterized. The purpose of this study was to investigate the frequency and age distribution of mammographic breast density patterns among a group of Chinese screening women and breast cancer patients in order to provide useful information for age-specific guidelines for breast cancer screening in Chinese women. METHODS: A retrospective review of a total of 3,394 screening women between August and December 2009 and 2,527 breast cancer patients between July 2011 and June 2012 was conducted. Descriptive analyses were used to examine the association between age and breast density. The significance of differences of breast density between the screening women and the breast cancer patients was examined using nonparametric tests. RESULTS: There was a significant inverse relationship between age and breast density overall (r=-0.37, p<0.01). Breast density of the breast cancer patients in the subgroups of 40-49 years old was greater compared with that of the screening women, the same in those aged 50-54 years and in those 55 years old or older, less than in the screening group. CONCLUSIONS: With regard to the Chinese women younger than 55 years old, the diagnostic efficiency of breast cancer screening imaging examinations may be potentially improved by combining screening mammography with ultrasound. PMID- 25124635 TI - Relationship between the SER treatment period and prognosis of patients with small cell lung cancer. AB - PURPOSE: To explore the relationship between SER (time between the start of any treatment and the end of radiation therapy) and the survival of patients with limited-stage small cell lung cancer. MATERIALS AND METHODS: Between 2008 and 2013, 135 cases of limited-stage small cell lung cancer (LS-SCLC) treated with consecutively curative chemoradiotherapy were included in this retrospective analysis. In terms of SER, patients were divided into early radiotherapy group (SER<30 days, n=76) and late radiotherapy group (SER>=30 days, n=59) with a cut- off of SER 30 days. Outcomes of the two groups were compared for overall survival. RESULTS: For all analyzable patients, median follow-up time was 23.8 months and median overall survival time was 16.8 months. Although there was no significant differences in distant metastasis free survival between the two groups, patients in early radiotherapy group had a significantly better PFS (p=0.003) and OS (p=0.000). CONCLUSIONS: A short SER may be a good prognostic factor for LD-SCLC patients treated with concurrent chemoradiotherapy. PMID- 25124636 TI - Mean platelet volume as a prognostic marker in metastatic colorectal cancer patients treated with bevacizumab-combined chemotherapy. AB - BACKGROUND: Recent studies have revealed a prognostic impact of the MPV (mean platelet volume)/platelet count ratio in terms of survival in advanced non-small cell lung cancer. However, there has been no direct analysis of the survival impact of MPV in patients with mCRC. The aim of the study is to evaluate the pretreatment MPV of patients with metastatic and non-metastatic colorectal cancer (non-mCRC) and also the prognostic significance of pretreatment MPV to progression in mCRC patients treated with bevacizumab-combined chemotherapy. MATERIALS AND METHODS: Fifty-three metastatic and ninety-five non-metastatic colorectal cancer patients were included into the study. Data on sex, age, lymph node status, MPV, platelet and platecrit (PCT) levels were obtained retrospectively from the patient medical records. RESULTS: The MPV was significantly higher in the patients with mCRC compared to those with non-mCRC (7.895+/-1.060 versus 7.322+/-1.136, p=0.013). The benefit of bevacizumab on PFS was significantly greater among the patients with low MPV than those with high MPV. The hazard ratio (HR) of disease progression was 0.41 (95%CI, 0.174-0.986; p=0.04). In conclusion, despite the retrospective design and small sample size, MPV can be considered a prognostic factor for mCRC patients treated with bevacizumab-combined chemotherapy. PMID- 25124638 TI - Dimethylnitrosamine-induced reduction in the level of poly-ADP-ribosylation of histone proteins of blood lymphocytes--a sensitive and reliable biomarker for early detection of cancer. AB - Poly-ADP-ribosylation (PAR) is a post-translational modification of mainly chromosomal proteins. It is known to be strongly involved in several molecular events, including nucleosome-remodelling and carcinogenesis. In this investigation, it was attempted to evaluate PAR level as a reliable biomarker for early detection of cancer in blood lymphocyte histones. PAR of isolated histone proteins was monitored in normal and dimethylnitrosamine (DMN)-exposed mice tissues using a novel ELISA-based immuno-probe assay developed in our laboratory. An inverse relationship was found between the level of PAR and period of DMN exposure in various histone proteins of blood lymphocytes and spleen cells. With the increase in the DMN exposure period, there was reduction in the PAR level of individual histones in both cases. It was also observed that the decrease in the level of PAR of histones resulted in progressive relaxation of genomic DNA, perhaps triggering activation of genes that are involved in initiation of transformation. The observed effect of carcinogen on the PAR of blood lymphocyte histones provided us with a handy tool for monitoring biochemical or physiological status of individuals exposed to carcinogens without obtaining biopsies of cancerous tissues, which involves several medical and ethical issues. Obtaining blood from any patient and separating blood lymphocytes are routine medical practices involving virtually no medical intervention, post-procedure medical care or trauma to a patient. Moreover, the immuno-probe assay is very simple, sensitive, reliable and cost-effective. Therefore, combined with the ease of preparation of blood lymphocytes and the simplicity of the technique, immuno probe assay of PAR has the potential to be applied for mass screening of cancer. It appears to be a promising step in the ultimate goal of making cancer detection simple, sensitive and reliable in the near future. PMID- 25124637 TI - Overexpression of HER-2/neu in patients with prostatic adenocarcinoma. AB - BACKGROUND: Prostatic adenocarcinoma is one of the main causes of cancer death, and its timely diagnosis and preventing its progression dramatically helps improve life indexes. Given the high disease recurrence rate, today, research is more inclined toward exploring causes of recurrence and development, and innovation of modern treatment methods. Several studies have explored over expression of human epidermal growth factor receptor 2 (HER-2/neu) in prostatic cancer so far, with different results. Thus, it was decided to investigate HER 2/neu overexpression in patients with prostatic adenocarcinoma in Iran. MATERIALS AND METHODS: A sample size of 40 patients with prostate cancer entered the study, using a cross-sectional, non-randomized sampling method. Parameters studied included patient age at surgery, Gleason score, serum prostatic specific antigen (PSA) before surgery, and positive sample rate after immunohistochemical staining to investigate HER-2/neu overexpression. RESULTS: In terms of HER-2/neu receptor staining rate, of 40 slides, 16 (40%) scored 0, 13 (32.5%) 1+, 7 (17.5%) 2+, and 4 (10%) 3+. In total 27.5% of slides showed HER-2/neu overexpression. In terms of age, an inverse correlation was found (-0.181), but without significance (p=0.263). In terms of serum PSA, the correlation coefficient was 0.449 (p=0.004). With respect to Gleason score, the coefficient was 0.190 (p=0.240). CONCLUSIONS: In this study, HER-2/neu overexpression occurred in 27.5% of prostate cancer cases, which is a relatively high figure, compared to similar studies elsewhere. While, we failed to reveal any relationship between HER-2/neu expression status with progression and prognosis of disease, it was demonstrated that the serum PSA level was significantly higher in cases with increased receptor expression. PMID- 25124639 TI - Downregulation of Cdk1 and cyclinB1 expression contributes to oridonin-induced cell cycle arrest at G2/M phase and growth inhibition in SGC-7901 gastric cancer cells. AB - BACKGROUND: Oridonin isolated from Rabdosia rubescens, a plant used to treat cancer in Chinese folk medicine, is one of the most important antitumor active ingredients. Previous studies have shown that oridonin has anti- tumor activities in vivo and in vitro, but little is known about cell cycle effects of oridonin in gastric cancer. MATERIALS AND METHODS: MTT assay was adopted to detect the proliferation inhibition of SGC-7901 cells, the cell cycle was assessed by flow cytometry and protein expression by Western blotting. RESULTS: Oridonin could inhibit SGC-7901 cell proliferation, the IC50 being 15.6 MUM, and blocked SGC 7901 cell cycling in the G2/M phase. The agent also decreased the protein expression of cyclinB1 and CDK1. CONCLUSIONS: Oridonin may inhibit SGC-7901 growth and block the cells in the G2/M phase by decreasing Cdk1 and cyclinB1 proteins. PMID- 25124640 TI - Baseline stimulated thyroglobulin level as a good predictor of successful ablation after adjuvant radioiodine treatment for differentiated thyroid cancers. AB - BACKGROUND: To determine the predictive value of the baseline stimulated thyroglobulin (STg) level for ablation outcome in patients undergoing adjuvant remnant radioiodine ablation (RRA) for differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: This retrospective study accrued 64 patients (23 male and 41 female; mean age of 40+/-14 years) who had total thyroidectomy followed by RRA for DTC from January 2012 till April 2014. Patients with positive anti-Tg antibodies and distant metastasis on post-ablative whole body iodine scans (TWBIS) were excluded. Baseline STg was used to predict successful ablation (follow-up STg<2 ng/ml, negative diagnostic WBIS and negative ultrasound neck) at 7-12 months follow-up. RESULTS: Overall, successful ablation was noted in 37 (58%) patients while ablation failed in 27 (42%). Using the ROC curve, a cut-off level of baseline STg level of <=14.5 ng/ml was found to be most sensitive and specific for predicting successful ablation. Successful ablation was thus noted in 25/28 (89%) of patients with baseline STg<=14.5 ng/ml and 12/36 (33%) patients with baseline STg>14.5 ng/ml ((p value<0.05). Age>40 years, female gender, PTS>2 cm, papillary histopathology, positive cervical nodes and positive TWBIS were significant predictors of ablation failure. CONCLUSIONS: We conclude that in patients with total thyroidectomy followed by I-131 ablation for DTC, the baseline STg level is a good predictor of successful ablation based on a stringent triple negative criteria (i.e. follow-up STg <2 ng/ ml, a negative DWBIS and a negative US neck). PMID- 25124641 TI - Albumin-globulin ratio for prediction of long-term mortality in lung adenocarcinoma patients. AB - BACKGROUND: Prior studies showed a relationship between serum albumin and the albumin to globulin ratio with different types of cancer. We aimed to evaluate the predictive value of the albumin-globulin ratio (AGR) for survival of patients with lung adenocarcinoma. MATERIALS AND METHODS: This retrospective study included 240 lung adenocarcinoma patients. Biochemical parameters before chemotherapy were collected and survival status was obtained from the hospital registry. The AGR was calculated using the equation AGR=albumin/ (total protein albumin) and ranked from lowest to highest, the total number of patients being divided into three equal tertiles according to the AGR values. Furthermore, AGR was divided into two groups (low and high tertiles) for ROC curve analysis. Cox model analysis was used to evaluate the prognostic value of AGR and AGR tertiles. RESULTS: The mean survival time for each tertile was: for the 1st 9.8 months (95%CI:7.765-11.848), 2nd 15.4 months (95%CI:12.685-18.186), and 3rd 19.9 months (95%CI:16.495-23.455) (p<0.001). Kaplan-Meier curves showed significantly higher survival rates with the third and high tertiles of AGR in comparison with the first and low tertiles, respectively. At multivariate analysis low levels of albumin and AGR, low tertile of AGR and high performance status remained an independent predictors of mortality. CONCLUSIONS: Low AGR was a significant predictor of long-term mortality in patients with lung adenocarcinoma. Serum albumin measurement and calculation of AGR are easily accessible and cheap to use for predicting mortality in patients with lung adenocarcinoma. PMID- 25124643 TI - Stathmin 1, a therapeutic target in esophageal carcinoma? PMID- 25124642 TI - Five-year survival and median survival time of nasopharyngeal carcinoma in Hospital Universiti Sains Malaysia. AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) is the fourth most common cancer in Malaysia. The objective of this study was to determine the five-year survival rate and median survival time of NPC patients in Hospital Universiti Sains Malaysia (USM). METHODS: One hundred and thirty four NPC cases confirmed by histopathology in Hospital USM between 1st January 1998 and 31st December 2007 that fulfilled the inclusion and exclusion criteria were retrospectively reviewed. Survival time of NPC patients were estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare survival of cases among presenting symptoms, WHO type, TNM classification and treatment modalities. RESULTS: The overall five-year survival rate of NPC patients was 38.0% (95% confidence interval (CI): 29.1, 46.9). The overall median survival time of NPC patients was 31.30 months (95%CI: 23.76, 38.84). The significant factors that altered the survival rate and time were age (p=0.041), cranial nerve involvement (p=0.012), stage (p=0.002), metastases (p=0.008) and treatment (p<0.001). CONCLUSION: The median survival of NPC patients is significantly longer for age<=50 years, no cranial nerve involvement, and early stage and is dependent on treatment modalities. PMID- 25124644 TI - Fast cell cycle analysis for intraoperative characterization of brain tumor margins and malignancy. AB - Flow cytometry, although indispensable for the characterization of hematologic malignancies, has not been extensively evaluated in solid tumors. To date intraoperative pathology evaluation of frozen sections of tissue obtained during surgery is the gold standard for intraoperative diagnosis. We investigated the value of a modified rapid protocol for cell cycle analysis for the intraoperative characterization of intracranial lesions and their surgical margins. We investigated patients who underwent surgery for an intracranial lesion suspicious for a tumor. DNA analysis and frozen sections were performed on tumor samples that were taken during surgery. Thirty-one patients met the inclusion criteria for the study. There was a significant difference in G0/G1 phase between high grade and low-grade tumors. Receiver operating characteristic (ROC) analysis provided 75% of G0/G1 fraction as the optimal cutoff value thresholding the discrimination between low and high-grade tumors. There was a significant difference in S-phase and mitoses fraction between high-grade and low-grade tumors. ROC analysis indicated 6% of S-phase and 9.7% of mitoses as the optimal cutoff values thresholding the discrimination between these two groups. In the glioblastoma patients, we also analyzed the perilesional tissue and found significant differences between tumor mass and margins regarding the G0/G1 phase, the S-phase and mitoses fraction. In conclusion rapid cell cycle analysis is a method capable of differentiating low from high-grade tumors and delineating tumor margins in gliomas. Thus, the role of cell cycle analysis in brain tumors warrants further investigation. PMID- 25124645 TI - Coccidioides parenchymal cerebral abscess in the setting of lymphoma. AB - Coccidioides immitis is a dimorphic fungus endemic to southwestern United States of America. When symptomatic, infection usually results in a subacute respiratory infection. Disseminated coccidioidomycosis occurs in less than 1% of all cases. We report a patient with follicular lymphoma and recent travel to Arizona, who underwent resection of a cerebral Coccidioides abscess. Serology testing was negative. This case highlights the importance of clinical suspicion in patients with neurologic symptoms and travel to an endemic location. PMID- 25124646 TI - Obsessive compulsive disorder due to a cavernous malformation hemorrhage in the dominant caudate head. AB - Structural lesions of the basal ganglia may lead to obsessive compulsive disorder (OCD). We report a 31-year-old woman who developed OCD after a previously asymptomatic left caudate intracerebral cavernous malformation (ICM) hemorrhaged. Her neurologic examination was normal. Her OCD required hospitalization and improved with medication and therapy. The pathophysiology of this psychiatric disorder probably reflects a frontal cortex deafferentation mechanism. In patients with known ICM, any abrupt change in neurologic or psychiatric symptoms should prompt repeat imaging to assess for hemorrhage. PMID- 25124647 TI - Weight and fat distribution in patients taking valproate: a valproate-discordant gender-matched twin and sibling pair study. AB - OBJECTIVES: Chronic treatment with valproate (VPA) is commonly associated with weight gain, which potentially has important health implications, in particular increased central fat distribution. We utilized a VPA-discordant same-sex, twin and matched sibling pair study design to primarily examine for differences in fat distribution between patients with epilepsy treated with VPA compared to their matched twin or sibling control. Weight, blood pressure, and leptin levels were assessed. METHODS: Height, weight, waist and hip measurements, exercise, blood pressure (BP), and serum leptin levels were measured. Body composition was measured using dual-energy x-ray absorptiometry (DXA). Abdominal fat was expressed as a percentage of the abdominal region (AFat%); and of whole body fat (WBF); (AFat%WBF). Mean within-pair differences were assessed (VPA-user and nonuser). Restricted maximum likelihood (REML) linear mixed model analysis was fitted to examine associations of anthropometrics, zygosity, gender, menopausal status, VPA dose and duration, with weight and AFat%. RESULTS: We studied 19 pairs of VPA-discordant, gender-matched (five male, 14 female) twins and siblings. Mean (standard deviation, SD) duration of therapy for VPA users was 11.0 (7.4) years. There were no statistically significant within-pair differences in age, height, weight, body mass index (BMI), BP, leptin level, WBF, AFat%, or AFat%WBF. For pairs in which VPA-user was treated for >11 years there were statistically significant mean within-pair differences in AFat%, (+7.1%, p = 0.03, n = 10 pairs), mean BP (+11.0 mm Hg, p = 0.006, n = 8 pairs); but not in AFat%WBF. VPA duration was positively associated with weight (estimate +0.98 kg/per year of VPA, p = 0.03); VPA treatment duration and dose were not significantly associated with AFat%. SIGNIFICANCE: This study demonstrated a relationship between long-term VPA use and abdominal adiposity (AFat%), which could have significant health implications. We recommend ongoing monitoring of weight, BMI, and blood pressure for patients taking VPA. PMID- 25124648 TI - Prevalence and predictors of genito-pelvic pain in pregnancy and postpartum: the prospective impact of fear avoidance. AB - INTRODUCTION: There is limited knowledge regarding the symptom profile of genito pelvic pain in pregnancy and postpartum, and potential psychosocial predictors of this pain. Prior studies have reported a positive association between prepregnancy pain and postpartum genito-pelvic pain. Greater fear avoidance has been associated with increased genital pain intensity in women, unrelated to childbirth. This relationship has not been examined prospectively in a postpartum population. AIMS: The study aims were to examine the symptom profile of genito pelvic pain during pregnancy and at 3 months postpartum, and the impact of prepregnancy nongenito-pelvic pain and fear avoidance in pregnancy on genito pelvic pain at 3 months postpartum. METHODS: First-time expectant mothers (N = 150) completed measures of fear avoidance (pain-related anxiety, catastrophizing, hypervigilance to pain), prepregnancy nongenito-pelvic pain, childbirth-related risk factors (e.g., episiotomy), and breastfeeding. MAIN OUTCOME MEASURES: Those reporting genito-pelvic pain in pregnancy and/or at 3 months postpartum answered questions about the onset (prepregnancy, during pregnancy, postpartum) and location (genital, pelvic, or both) of the pain and rated the intensity and unpleasantness of the pain on numerical rating scales. RESULTS: Of 150 women, 49% reported genito-pelvic pain in pregnancy. The pain resolved for 59% of women, persisted for 41%, and 7% of women reported a new onset of genito-pelvic pain after childbirth. Prepregnancy nongenito-pelvic pain was associated with an increased likelihood of postpartum onset of genito-pelvic pain. Greater pain related anxiety was associated with greater average genito-pelvic pain intensity at 3 months postpartum. CONCLUSIONS: Results suggest that about half of women may develop genito-pelvic pain during pregnancy, which will persist for about a third, and a subset will develop this pain after childbirth. Prior recurrent nongenito-pelvic pain may enhance the risk of developing genito-pelvic pain postpartum, while greater pain-related anxiety in pregnancy may increase the risk for greater intensity of postpartum genito-pelvic pain. PMID- 25124649 TI - EEG feature pre-processing for neonatal epileptic seizure detection. AB - Aim of our project is to further optimize neonatal seizure detection using support vector machine (SVM). First, a Kalman filter (KF) was used to filter both feature and classifier output time series in order to increase temporal precision. Second, EEG baseline feature correction (FBC) was introduced to reduce inter patient variability in feature distributions. The performance of the detection methods is evaluated on 54 multi channel routine EEG recordings from 39 both term and pre-term newborns. The area under the receiver operating characteristics curve (AUC) as well as sensitivity and specificity are used to evaluate the performance of the classification method. SVM without KF and FBC achieves an AUC of 0.767 (sensitivity 0.679, specificity 0.707). The highest AUC of 0.902 (sensitivity 0.801, specificity 0.831) is achieved on baseline corrected features with a Kalman smoother used for training data pre-processing and a KF used to filter the classifier output. Both FBC and KF significantly improve neonatal epileptic seizure detection. This paper introduces significant improvements for the state of the art SVM based neonatal epileptic seizure detection. PMID- 25124650 TI - An experimental and numerical investigation of head dynamics due to stick impacts in girls' lacrosse. AB - A method of investigating head acceleration and intracranial dynamics from stick impacts in girls' and women's lacrosse was developed using headform impact experiments and a finite element head model. Assessing the likelihood of head injury due to stick-head impacts is of interest in girls' and women's lacrosse due to the current lack of head protection during play. Experimental and simulation data were compared to characterize the head acceleration caused by stick-head impacts. Validation against cadaver head impact experiments ensures that the finite element model, with its relatively simple material properties, can provide means to develop a better understanding of the intracranial dynamics during lacrosse stick impacts. Our numerical results showed the peak acceleration at the center of gravity increased linearly with impact force, and was generally in agreement with the experimental data. von Mises stresses and peak principal strains, two common literature injury indicators, were examined within the finite element model, and peak values were below the previously reported thresholds for mild traumatic brain injury. By reconstructing typical in-game, unprotected stick head impacts, this investigation lays the foundation for a quantitative methodology of injury prediction in girls' and womens' lacrosse. PMID- 25124651 TI - Individual and community-level determinants of mental and physical health after the deepwater horizon oil spill: findings from the gulf States population survey. AB - The 2010 Deepwater Horizon oil spill had enormous consequences on the environment. Prevalence of mental and physical health conditions among Gulf residents after the disaster, however, are still being assessed. The Gulf State Population Survey (GSPS) was a representative survey of 38,361 residents in four Gulf States and was conducted from December 2010 to December 2011. Analysis of the GSPS data showed that differences in individual characteristics and direct or indirect exposure to the disaster drove the individual-level variation in health outcomes (mental distress, physical distress, and depression). Direct exposure to the disaster itself was the most important determinant of health after this event. Selected county-level characteristics were not found to be significantly associated with any of our health indicators of interest. This study suggests that in the context of an overwhelming event, persons who are most directly affected through direct exposure should be the primary focus of any public health intervention effort. PMID- 25124653 TI - Oncometabolites-driven tumorigenesis: From genetics to targeted therapy. AB - Although the alteration of cellular metabolism in cancer was reported by Warburg in the early 1930s, a regain of interest in cancer metabolism has more recently followed the discovery of germline or somatic mutations in genes coding for metabolic enzymes (succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase) that are associated with tumor susceptibility. Mutations in these genes are found in numerous tumor types including paragangliomas, kidney cancers, leiomyomas, glioblastomas and acute myeloid leukemia. They lead to the accumulation of so-called oncometabolites that behave as competitors of 2 oxoglutarate-dependent dioxygenases, involved in a broad spectrum of pathways such as hypoxic response and epigenetic reprogramming. Here, we review the diverse pathways affected by oncometabolites, their potential role in cancer formation, maintenance, metastasis and sensitivity to chemotherapies, as well as emerging new therapeutic strategies. PMID- 25124654 TI - Reversal of toxic manifestations of chlorpromazine. PMID- 25124652 TI - Differential Effects of Mental Health Problems Among Truant Youths. AB - Research indicates at-risk youth are more likely to experience emotional and psychological problems. Young people who are often truant from school represent a group of at-risk youth, but one for which mental health issues are understudied. This study examined heterogeneity of mental health problems among a sample of 300 truant adolescents using latent class analysis (LCA). LCA indicated the sample of truants was best represented by four latent subgroups of youth with low mental health problems; high depression, low mania; high mania, low depression; and high depression and mania. These subgroups were examined in relation to sociodemographic and psychosocial measures at baseline and after truancy offenses. Results indicated general and unique differences in these covariates across the four latent classes. Service and practice implications of better understanding mental health issues of truant youth are discussed. PMID- 25124655 TI - Sensory differences between beet and cane sugar sources. AB - Research concerning the sensory properties of beet and cane sugars is lacking in the scientific literature. Therefore, the objectives of this research were to determine whether a sensory difference was perceivable between beet and cane sugar sources in regard to their (1) aroma-only, (2) aroma and taste without nose clips, and (3) taste-only with nose clips, and to characterize the difference between the sugar sources using descriptive analysis. One hundred panelists evaluated sugar samples using a tetrad test. A significant difference (P < 0.05) was identified between beet and cane sugar sources when evaluated by aroma-only and taste and aroma without nose clips. However, there was no difference when tasted with nose clips. To characterize the observed differences, ten trained panelists identified and quantified key sensory attributes of beet and cane sugars using descriptive analysis. Analysis of variance indicated significant differences (P < 0.05) between sugar samples for 8 of the 10 attributes including: off-dairy, oxidized, earthy, and barnyard aroma, fruity and burnt sugar aroma-by-mouth, sweet aftertaste, and burnt sugar aftertaste. The sensory profile of beet sugar was characterized by off-dairy, oxidized, earthy, and barnyard aromas and by a burnt sugar aroma-by-mouth and aftertaste, whereas cane sugar was characterized by a fruity aroma-by-mouth and sweet aftertaste. This study shows that beet and cane sugar sources can be differentiated by their aroma and provides a sensory profile characterizing the differences. As sugar is used extensively as a food ingredient, sensory differences between beet and cane sugar sources once incorporated into different product matrices should be studied as a next step. PMID- 25124656 TI - Identification of Malassezia species in the facial lesions of Chinese seborrhoeic dermatitis patients based on DNA sequencing. AB - The genus Malassezia is important in the aetiology of facial seborrhoeic dermatitis (FSD), which is the most common clinical type. The purpose of this study was to analyse the distribution of Malassezia species in the facial lesions of Chinese seborrhoeic dermatitis (SD) patients and healthy individuals. Sixty four isolates of Malassezia were isolated from FSD patients and 60 isolates from healthy individuals. Sequence analysis of the internal transcribed spacer (ITS) region was used to identify the isolates. The most frequently identified Malassezia species associated with FSD was M. furfur (76.56%), followed by M. sympodialis (12.50%) and M. japonica (9.38%). The most frequently isolated species in healthy individuals were M. furfur (61.67%), followed by M. sympodialis (25.00%), M. japonica (6.67%), M. globosa (3.33%), and M. obtusa (3.33%). Overall, our study revealed that while M. furfur is the predominant Malassezia species in Chinese SD patients, there is no significant difference in the distribution of Malassezia species between Chinese SD patients and healthy individuals. PMID- 25124658 TI - Duelling letters: which one would you sign? PMID- 25124657 TI - New less invasive ventricular reconstruction technique in the treatment of ischemic heart failure. AB - Ischemic cardiomyopathy is the leading cause of heart failure. In patients with left ventricular (LV) dilatation, low ejection fraction, and transmural scar in an anteroseptal distribution, surgical ventricular reconstruction (SVR) is a treatment option. We describe our first experience with the Less Invasive Ventricular Enhancement (LIVE) technique using the ReviventTM system (Bioventrix Inc., San Ramon, CA), in the treatment of a large anteroapical aneurysm. PMID- 25124661 TI - Epigenetic epidemiology of cancer. AB - Epigenetic epidemiology includes the study of variation in epigenetic traits and the risk of disease in populations. Its application to the field of cancer has provided insight into how lifestyle and environmental factors influence the epigenome and how epigenetic events may be involved in carcinogenesis. Furthermore, it has the potential to bring benefit to patients through the identification of diagnostic markers that enable the early detection of disease and prognostic markers that can inform upon appropriate treatment strategies. However, there are a number of challenges associated with the conduct of such studies, and with the identification of biomarkers that can be applied to the clinical setting. In this review, we delineate the challenges faced in the design of epigenetic epidemiology studies in cancer, including the suitability of blood as a surrogate tissue and the capture of genome-wide DNA methylation. We describe how epigenetic epidemiology has brought insight into risk factors associated with lung, breast, colorectal and bladder cancer and review relevant research. We discuss recent findings on the identification of epigenetic diagnostic and prognostic biomarkers for these cancers. PMID- 25124662 TI - Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo. AB - Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignant transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis. PMID- 25124664 TI - Epistasis effects of COMT and MTHFR on inter-individual differences in mental health: under the inverted U-shaped prefrontal dopamine model. AB - Higher cognitive performance, maintenance of mental health and psychological well being require adequate prefrontal cortex (PFC) function. "Inverted U-shaped" dopamine model indicates optimal PFC dopamine level is important to attain its function while high or low levels have adverse effects. Catechol-O methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR) may be involved in this complex non-linear PFC dopamine regulation. We addressed whether genetic variation reflecting COMT and MTHFR activities can explain the inter individual mental health differences in healthy Japanese men (n=188). The mental health was measured by Mental Health Inventory (MHI)-5 score. The rs4633-rs4818 rs4680 haplotypes were used to represent the multilevel COMT activities, while for MTHFR, the functional single polymorphism, rs1801133 (C677T), was used. We examined the effectiveness of haplotype-based association analysis of COMT on mental health together with studying its interaction with MTHFR-C677T. As a result, the relation between activity-ranked COMT genotype and MHI-5 score showed a tendency to fit into an "inverted U-shaped" quadratic curve (P=0.054). This curvilinear correlation was significant in the subjects with MTHFR-CC (P<0.001), but not with MTHFR T-allele carriers (P=0.793). Our pilot study implies a potential influence of COMT and MTHFR genotypic combination on normal variation of mental health. PMID- 25124665 TI - Nascent histamine induces alpha-synuclein and caspase-3 on human cells. AB - Histamine (Hia) is the most multifunctional biogenic amine. It is synthetized by histidine decarboxylase (HDC) in a reduced set of mammalian cell types. Mast cells and histaminergic neurons store Hia in specialized organelles until the amine is extruded by exocytosis; however, other immune and cancer cells are able to produce but not store Hia. The intracellular effects of Hia are still not well characterized, in spite of its physiopathological relevance. Multiple functional relationships exist among Hia metabolism/signaling elements and those of other biogenic amines, including growth-related polyamines. Previously, we obtained the first insights for an inhibitory effect of newly synthetized Hia on both growth related polyamine biosynthesis and cell cycle progression of non-fully differentiated mammalian cells. In this work, we describe progress in this line. HEK293 cells were transfected to express active and inactive versions of GFP human HDC fusion proteins and, after cell sorting by flow cytometry, the relative expression of a large number of proteins associated with cell signaling were measured using an antibody microarray. Experimental results were analyzed in terms of protein-protein and functional interaction networks. Expression of active HDC induced a cell cycle arrest through the alteration of the levels of several proteins such as cyclin D1, cdk6, cdk7 and cyclin A. Regulation of alpha synuclein and caspase-3 was also observed. The analyses provide new clues on the molecular mechanisms underlying the regulatory effects of intracellular newly synthetized Hia on cell proliferation/survival, cell trafficking and protein turnover. This information is especially interesting for emergent and orphan immune and neuroinflammatory diseases. PMID- 25124663 TI - Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1alpha in ameloblastoma. AB - Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1alpha than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1alpha antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas. PMID- 25124666 TI - Expression and localization of aquaporin-4 in sensory ganglia. AB - Aquaporin-4 (AQP4) is a water channel protein that is predominantly expressed in astrocytes in the CNS. The rapid water flux through AQP4 may contribute to electrolyte/water homeostasis and may support neuronal activities in the CNS. On the other hand, little is known about the expression of AQP4 in the peripheral nervous system (PNS). Using AQP4(-/-) mice as a negative control, we demonstrated that AQP4 is also expressed in sensory ganglia, such as trigeminal ganglia and dorsal root ganglia in the PNS. Immunohistochemistry revealed that AQP4 is exclusively localized to satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in the sensory ganglia. Biochemical analyses revealed that the expression levels of AQP4 in sensory ganglia were considerably lower than those in astrocytes in the CNS. Consistently, behavioral analyses did not show any significant difference in terms of mechanical and cold sensitivity between wild type and AQP4(-/-) mice. Overall, although the pathophysiological relevance of AQP4 in somatosensory perception remains unclear, our findings provide new insight into the involvement of water homeostasis in the peripheral sensory system. PMID- 25124667 TI - Human decidual stromal cells secrete soluble pro-apoptotic factors during decidualization in a cAMP-dependent manner. AB - STUDY QUESTION: Is there a relationship between decidualization and apoptosis of decidual stromal cells (DSC)? SUMMARY ANSWER: Decidualization triggers the secretion of soluble factors that induce apoptosis in DSC. WHAT IS KNOWN ALREADY: The differentiation and apoptosis of DSC during decidualization of the receptive decidua are crucial processes for the controlled invasion of trophoblasts in normal pregnancy. Most DSC regress in a time-dependent manner, and their removal is important to provide space for the embryo to grow. However, the mechanism that controls DSC death is poorly understood. STUDY DESIGN, SIZE, DURATION: The apoptotic response of DSC was analyzed after exposure to different exogenous agents and during decidualization. The apoptotic potential of decidualized DSC supernatants and prolactin (PRL) was also evaluated. PARTICIPANTS/MATERIALS, SETTING, METHODS: DSC lines were established from samples of decidua from first trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production, as a marker of decidualization, was determined by enzyme-linked immunosorbent assay. MAIN RESULTS AND THE ROLE OF CHANCE: DSCs were resistant to a variety of apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during decidualization in culture, with cAMP being essential for both apoptosis and differentiation. In addition, culture supernatants from decidualized DSC induced apoptosis in undifferentiated DSC, although paradoxically these supernatants decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL receptor did not decrease the apoptosis induced by supernatants. LIMITATIONS, REASONS FOR CAUTIONS: Further studies are needed to examine the involvement of other soluble factors secreted by decidualized DSC in the induction of apoptosis. WIDER IMPLICATIONS OF THE FINDINGS: The present results indicate that apoptosis of DSC occurs in parallel to differentiation, in response to decidualization signals, with soluble factors secreted by decidualized DSC being responsible for triggering cell death. These studies are relevant in the understanding of how the regression of decidua, a crucial process for successful pregnancy, takes place. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Consejeria de Economia, Innovacion y Ciencia, Junta de Andalucia (Grant CTS-6183, Proyectos de Investigacion de Excelencia 2010 to C.R.-R.) and the Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, Spain (Grants PS09/00339 and PI12/01085 to E.G.O.). E.L.-D. was supported by fellowships from the Ministerio de Educacion y Ciencia, Spain and the University of Granada. The authors have no conflict of interest. PMID- 25124669 TI - Endometrial signals improve embryo outcome: functional role of vascular endothelial growth factor isoforms on embryo development and implantation in mice. AB - STUDY QUESTION: Does vascular endothelial growth factor (VEGF) have important roles during early embryo development and implantation? SUMMARY ANSWER: VEGF plays key roles during mouse preimplantation embryo development, with beneficial effects on time to cavitation, blastocyst cell number and outgrowth, as well as implantation rate and fetal limb development. WHAT IS KNOWN ALREADY: Embryo implantation requires synchronized dialog between maternal cells and those of the conceptus. Following ovulation, secretions from endometrial glands increase and accumulate in the uterine lumen. These secretions contain important mediators that support the conceptus during the peri-implantation phase. Previously, we demonstrated a significant reduction of VEGFA in the uterine cavity of women with unexplained infertility. Functional studies demonstrated that VEGF significantly enhanced endometrial epithelial cell adhesive properties and embryo outgrowth. STUDY DESIGN, SIZE, DURATION: Human endometrial lavages (n = 6) were obtained from women of proven fertility. Four-week old Swiss mice were superovulated and mated with Swiss males to obtain embryos for treatment with VEGF in vitro. Preimplantation embryo development was assessed prior to embryo transfer (n = 19 30/treatment group/output). Recipient F1 female mice (8-12 weeks of age) were mated with vasectomized males to induce pseudopregnancy and embryos were transferred. On Day 14.5 of pregnancy, uterine horns were collected for analysis of implantation rates as well as placental and fetal development (n = 14 19/treatment). PARTICIPANTS/MATERIALS, SETTING, METHODS: Lavage fluid was assessed by western immunoblot analysis to determine the VEGF isoforms present. Mouse embryos were treated with either recombinant human (rh)VEGF, or VEGF isoforms 121 and 165. Preimplantation embryo development was quantified using time-lapse microscopy. Blastocysts were (i) stained for cell number, (ii) transferred to wells coated with fibronectin to examine trophoblast outgrowth or (iii) transferred to pseudo pregnant recipients to analyze implantation rates, placental and fetal development. MAIN RESULTS AND THE ROLE OF CHANCE: Western blot analysis revealed the presence of VEGF121 and 165 isoforms in human uterine fluid. Time-lapse microscopy analysis revealed that VEGF (n = 22) and VEGF121 (n = 23) treatment significantly reduced the preimplantation mouse embryo time to cavitation (P < 0.05). VEGF and VEGF165 increased both blastocyst cell number (VEGF n = 27; VEGF165 n = 24: P < 0.001) and outgrowth (n = 15/treatment: 66 h, P < 0.001; 74, 90, 98 and 114 h, P < 0.01) on fibronectin compared with control. Furthermore, rhVEGF improved implantation rates and enhanced fetal limb development (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of this work, embryo development and implantation was only examined in the mouse. WIDER IMPLICATIONS OF THE FINDINGS: The absence or reduction in levels of VEGF during the preimplantation period likely affects key events during embryo development, implantation and placentation. The potential for improvement of clinical IVF outcomes by the addition of VEGF to human embryo culture media needs further investigation. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a University of Melbourne Early Career Researcher Grant #601040, the NHMRC (L.A.S., Program grant #494802; Fellowship #1002028; N.J.H., Fellowship # 628927; J.E.; project grant #1047756) and L.A.S., Monash IVF Research and Education Foundation. N.K.B. was supported by an Australian Postgraduate Award. Work at PHI-MIMR Institute was also supported by the Victorian Government's Operational Infrastructure Support Program. There are no conflicts of interest to declare. PMID- 25124668 TI - Clinically relevant enhancement of human sperm motility using compounds with reported phosphodiesterase inhibitor activity. AB - STUDY QUESTION: Can we identify compound(s) with reported phosphodiesterase inhibitor (PDEI) activity that could be added to human spermatozoa in vitro to enhance their motility without compromising other sperm functions? SUMMARY ANSWER: We have identified several compounds that produce robust and effective stimulation of sperm motility and, importantly, have a positive response on patient samples. WHAT IS KNOWN ALREADY: For >20 years, the use of non-selective PDEIs, such as pentoxifylline, has been known to influence the motility of human spermatozoa; however, conflicting results have been obtained. It is now clear that human sperm express several different phosphodiesterases and these are compartmentalized at different regions of the cells. By using type-specific PDEIs, differential modulation of sperm motility may be achieved without adversely affecting other functions such as the acrosome reaction (AR). STUDY DESIGN, SIZE, DURATION: This was a basic medical research study examining sperm samples from normozoospermic donors and subfertile patients attending the Assisted Conception Unit (ACU), Ninewells Hospital Dundee for diagnostic semen analysis, IVF and ICSI. Phase 1 screened 43 commercially available compounds with reported PDEI activity to identify lead compounds that stimulate sperm motility. Samples were exposed (20 min) to three concentrations (1, 10 and 100 uM) of compound, and selected candidates (n = 6) progressed to Phase 2, which provided a more comprehensive assessment using a battery of in vitro sperm function tests. PARTICIPANTS/MATERIALS, SETTING, METHODS: All healthy donors and subfertile patients were recruited at the Medical Research Institute, University of Dundee and ACU, Ninewells Hospital Dundee (ethical approval 08/S1402/6). In Phase 1, poor motility cells recovered from the 40% interface of the discontinuous density gradient were used as surrogates for patient samples. Pooled samples from three to four different donors were utilized in order to reduce variability and increase the number of cells available for simultaneous examination of multiple compounds. During Phase 2 testing, semen samples from 23 patients attending for either routine diagnostic andrology assessment or IVF/ICSI were prepared and exposed to selected compounds. Additionally, 48 aliquots of prepared samples, surplus to clinical use, were examined from IVF (n = 32) and ICSI (n = 16) patients to further determine the effects of selected compounds under clinical conditions of treatment. Effects of compounds on sperm motility were assessed by computer-assisted sperm analysis. A modified Kremer test using methyl cellulose was used to assess sperm functional ability to penetrate into viscous media. Sperm acrosome integrity and induction of apoptosis were assessed using the acrosomal content marker PSA-FITC and annexin V kit, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In Phase 1, six compounds were found to have a strong effect on poor motility samples with a magnitude of response of >= 60% increase in percentage total motility. Under capacitating and non-capacitating conditions, these compounds significantly (P <= 0.05) increased the percentage of total and progressive motility. Furthermore, these compounds enhanced penetration into a cervical mucus substitute (P <= 0.05). Finally, the AR was not significantly induced and these compounds did not significantly increase the externalization of phosphatidylserine (P = 0.6, respectively). In general, the six compounds maintained the stimulation of motility over long periods of time (180 min) and their effects were still observed after their removal. In examinations of clinical samples, there was a general observation of a more significant stimulation of sperm motility in samples with lower baseline motility. In ICSI samples, compounds #26, #37 and #38 were the most effective at significantly increasing total motility (88, 81 and 79% of samples, respectively) and progressive motility (94, 93 and 81% of samples, respectively). In conclusion, using a two-phased drug discovery screening approach including the examination of clinical samples, 3/43 compounds were identified as promising candidates for further study. LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study and caution must be taken when extrapolating the results. Data for patients were from one assessment and thus the robustness of responses needs to be established. The n values for ICSI samples were relatively small. WIDER IMPLICATIONS OF THE FINDINGS: We have systematically screened and identified several compounds that have robust and effective stimulation (i.e. functional significance with longevity and no toxicity) of total and progressive motility under clinical conditions of treatment. These compounds could be clinical candidates with possibilities in terms of assisted reproductive technology options for current or future patients affected by asthenozoospermia or oligoasthenozoospermia. STUDY FUNDING/COMPETING INTERESTS: This study was funded primarily by the MRC (DPFS) but with additional funding from the Wellcome Trust, Tenovus (Scotland), University of Dundee, NHS Tayside and Scottish Enterprise. The authors have no competing interests. A patent (#WO2013054111A1) has been published containing some of the information presented in this manuscript. PMID- 25124671 TI - Effect of socioeconomic level on knowledge of stroke in the general population: A social inequality gradient. AB - OBJECTIVES: Socioeconomic status is a factor that influences health-related behaviour in individuals as well as health conditions in entire populations. The objective of the present study was to analyse the sociodemographic factors that may influence knowledge of stroke. METHOD: Cross-sectional study. A representative sample was selected by double randomisation. Face-to-face interviews were carried out by previously trained medical students using a structured questionnaire with open- and closed-ended questions. Adequate knowledge was previously defined. The Mantel-Haenszel test and adjusted logistic regression analysis were used to assess the association between knowledge of stroke and the study variables. RESULTS: 2411 subjects were interviewed (59.9% women; mean age 49.0 [SD 17.3] years) Seventy-three per cent were residents of urban areas, 24.7% had a university education, and 15.2% had a low level of schooling. Only 2.1% reported earning more than 40 000 euros/year, with 29.9% earning less than 10 000. Nearly 74% reported having an excellent or good state of health. The unemployment rate was 17.0%. Prevalence of "adequate knowledge" was 39.7% (95% CI: 37.7%-41.6%). Trend analysis showed an association between knowledge of stroke and income (z=10.14, P<0.0001); educational level (z=15.95, P<0.0001); state of health (z=7.92, P<0.0001); and employment status (z=8.98, P<0.0001). CONCLUSIONS: Educational level, income, employment status, and state of health are independent factors for adequate knowledge of stroke. Public awareness campaigns should present material using simple language and efforts should be directed toward the most disadvantaged social strata in particular. PMID- 25124670 TI - Use and acceptance of long lasting insecticidal net screens for dengue prevention in Acapulco, Guerrero, Mexico. AB - BACKGROUND: Dengue, recognized by the WHO as the most important mosquito-borne viral disease in the world, is a growing problem. Currently, the only effective way of preventing dengue is vector control. Standard methods have shown limited effect, and there have been calls to develop new integrated vector management approaches. One novel tool, protecting houses with long lasting insecticidal screens on doors and windows, is being trialled in a cluster randomised controlled trial by a joint UADY/WHO TDR/IDRC study in various districts of Acapulco, Mexico, with exceptionally high levels of crime and insecurity.This study investigated the community's perspectives of long lasting insecticidal screens on doors and windows in homes and in schools, in order to ascertain their acceptability, to identify challenges to further implementation and opportunities for future improvements. METHODS: This was a sequential mixed-methods study. The quantitative arm contained a satisfaction survey administered to 288 houses that had received the intervention examining their perspectives of both the intervention and dengue prevention in general. The qualitative arm consisted of Focus Group Discussions (FGDs) with those who had accepted the intervention and key informant interviews with: schoolteachers to discuss the use of the screens in schools, program staff, and community members who had refused the intervention. RESULTS: Overall satisfaction and acceptance of the screens was very high, with only some operational and technical complaints relating to screen fragility and the installation process. However, the wider social context of urban violence and insecurity was a major barrier to screen acceptance. Lack of information dissemination and community collaboration were identified as project weaknesses. CONCLUSIONS: The screens are widely accepted by the population, but the project implementation could be improved by reassuring the community of its legitimacy in the context of insecurity. More community engagement and better information sharing structures are needed.The screens could be a major new dengue prevention tool suitable for widespread use, if further research supports their entomological and epidemiological effectiveness and their acceptability in different social and environmental contexts. Further research is needed looking at the impact of insecurity of dengue prevention programmes. PMID- 25124672 TI - Regarding emergency department consultations with neurologists. Author's reply. PMID- 25124673 TI - Financial costs and personal consequences of research misconduct resulting in retracted publications. AB - The number of retracted scientific articles has been increasing. Most retractions are associated with research misconduct, entailing financial costs to funding sources and damage to the careers of those committing misconduct. We sought to calculate the magnitude of these effects. Data relating to retracted manuscripts and authors found by the Office of Research Integrity (ORI) to have committed misconduct were reviewed from public databases. Attributable costs of retracted manuscripts, and publication output and funding of researchers found to have committed misconduct were determined. We found that papers retracted due to misconduct accounted for approximately $58 million in direct funding by the NIH between 1992 and 2012, less than 1% of the NIH budget over this period. Each of these articles accounted for a mean of $392,582 in direct costs (SD $423,256). Researchers experienced a median 91.8% decrease in publication output and large declines in funding after censure by the ORI. PMID- 25124675 TI - Systemic lupus erythematosus complicated with liver cirrhosis in a patient with Papillon-Lefevre syndrome. AB - We report the first case of a girl who presented with Papillon-Lefevre syndrome (PLS) and subsequently developed systemic lupus erythematosus and liver cirrhosis. This indicates that autoimmune diseases can be a complication in patients with PLS. Cathepsin C gene mutations were not found in our patient or her mother. Thus, other genetic factors may have been involved in this patient. PMID- 25124674 TI - Considerations when investigating lncRNA function in vivo. AB - Although a small number of the vast array of animal long non-coding RNAs (lncRNAs) have known effects on cellular processes examined in vitro, the extent of their contributions to normal cell processes throughout development, differentiation and disease for the most part remains less clear. Phenotypes arising from deletion of an entire genomic locus cannot be unequivocally attributed either to the loss of the lncRNA per se or to the associated loss of other overlapping DNA regulatory elements. The distinction between cis- or trans effects is also often problematic. We discuss the advantages and challenges associated with the current techniques for studying the in vivo function of lncRNAs in the light of different models of lncRNA molecular mechanism, and reflect on the design of experiments to mutate lncRNA loci. These considerations should assist in the further investigation of these transcriptional products of the genome. PMID- 25124677 TI - Urine beta2-microglobulin is associated with clinical disease activity and renal involvement in female patients with systemic lupus erythematosus. AB - OBJECTIVE: We investigated the association of serum and urine beta2-microglobulin (beta2MG) with renal involvement and clinical disease activity in systemic lupus erythematosus (SLE). METHODS: Sixty-four female patients with SLE were enrolled. We assessed SLE disease activity (SLEDAI)-2K and measured serum and urine beta2MG levels, as well as complement (C3 and C4) and anti-dsDNA levels. According to the SLEDAI scores, two groups were categorized: low (0-5 of SLEDAI) and high (6-19 of SLEDAI) disease activity groups. The presence of renal involvement was determined by renal SLEDAI score. Statistical analysis was performed using Spearman's correlation analysis, Mann-Whitney U test, multivariate regression analysis, and logistic regression analysis. RESULTS: Urine beta2MG levels were significantly different between low and high SLEDAI groups (p = 0.001), but not for serum beta2MG levels (p = 0.579). Patients with renal involvement showed higher urine beta2MG levels compared to those without renal involvement (p < 0.001), but again there was not a difference in serum beta2MG levels (p = 0.228). Urine beta2MG was closely associated with SLEDAI (r = 0.363, p = 0.003), renal SLEDAI (r = 0.479, p < 0.001), urine protein/Cr (r = 0.416, p = 0.001), and ESR (r = 0.347, p = 0.006), but not serum beta2MG (r = 0.245, p = 0.051). Urine beta2MG level was identified as a surrogate for renal involvement (p = 0.009, OR = 1.017, 95% CI 1.004-1.030) and overall disease activity (p = 0.009, OR = 1.020, 95% CI 1.005 1.036). CONCLUSIONS: We demonstrated that urine beta2MG levels are associated with renal involvement and overall clinical disease activity in SLE. PMID- 25124678 TI - Elucidation of epithelial-mesenchymal transition-related pathways in a triple negative breast cancer cell line model by multi-omics interactome analysis. AB - In life sciences, and particularly biomedical research, linking aberrant pathways exhibiting phenotype-specific alterations to the underlying physical condition or disease is an ongoing challenge. Computationally, a key approach for pathway identification is data enrichment, combined with generation of biological networks. This allows identification of intrinsic patterns in the data and their linkage to a specific context such as cellular compartments, diseases or functions. Identification of aberrant pathways by traditional approaches is often limited to biological networks based on either gene expression, protein expression or post-translational modifications. To overcome single omics analysis, we developed a set of computational methods that allow a combined analysis of data collections from multiple omics fields utilizing hybrid interactome networks. We apply these methods to data obtained from a triple negative breast cancer cell line model, combining data sets of gene and protein expression as well as protein phosphorylation. We focus on alterations associated with the phenotypical differences arising from epithelial-mesenchymal transition in two breast cancer cell lines exhibiting epithelial-like and mesenchymal-like morphology, respectively. Here we identified altered protein signaling activity in a complex biologically relevant network, related to focal adhesion and migration of breast cancer cells. We found dysregulated functional network modules revealing altered phosphorylation-dependent activity in concordance with the phenotypic traits and migrating potential of the tested model. In addition, we identified Ser267 on zyxin, a protein coupled to actin filament polymerization, as a potential in vivo phosphorylation target of cyclin-dependent kinase 1. PMID- 25124679 TI - Distribution and accumulation of hexachlorobutadiene in soils and terrestrial organisms from an agricultural area, East China. AB - Hexachlorobutadiene (HCBD) is a potential persistent organic pollutant that has been found in abiotic environments and organisms. However, information on HCBD in soils and its accumulation in terrestrial food chains is scarce. This study investigated the accumulation of HCBD in soils, plants, and terrestrial fauna in a typical agricultural area in Eastern China, and drew comparisons with organochlorine pesticides (OCPs). The HCBD concentrations in soils were <0.02 3.1ng/g dry weight, which were similar to alpha-endosulfan concentrations but much lower than the concentrations of some other OCPs. The HCBD soil-plant accumulation factors, 8.5-38.1, were similar to those of o,p'-DDT and higher than those of HCHs and p,p'-DDT, indicating that HCBD is strongly bioaccumulated by rice and vegetables. HCBD concentrations of 1.3-8.2ng/g lipid weight were found in herbivorous insects, earthworms, and Chinese toads. The biomagnification factor, the ratio between the lipid-normalized concentrations in the predator and the prey, was found to be 0.16-0.64 for different food chains of Chinese toads, so HCBD was found not to biomagnify, which is in contrast with OCPs. Further research into whether HCBD is biomagnified in high trophic level organisms or through the entire terrestrial food web is required. PMID- 25124676 TI - Anti-C1q antibodies in systemic lupus erythematosus. AB - OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8 38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis. PMID- 25124680 TI - Proteomics study of silver nanoparticles toxicity on Oryza sativa L. AB - The increasing use of silver nanoparticles, (AgNPs), will inevitably result in their release into the environment and thereby cause the exposure to plants. It was claimed that using AgNPs is a safe and efficient method to preserve and treat agents of disease in agriculture. This study tries to understand the protein populations and sub-populations and follow up environmental AgNPs stresses. To accomplish these, the action of homemade spherical AgNPs colloidal suspension against Oryza sativa L. was investigated by a proteomic approach (2-DE and NanoLC/FT-ICR MS identification). Twenty-eight responsive (decrement/increment in abundance) proteins were identified. Proteomic results revealed that an exposure of O. sativa L., root with different concentrations of AgNPs resulted in an accumulation of protein precursors, indicative of the dissipation of a proton motive force. The identified proteins are involved in oxidative stress tolerance, Ca(2+) regulation and signaling, transcription and protein degradation, cell wall and DNA/RNA/protein direct damage, cell division and apoptosis. The expression pattern of these proteins and their possible involvement in the nontoxicity mechanisms were discussed. PMID- 25124682 TI - Mild to Moderate Renal Impairment Is Associated With No-Reflow Phenomenon After Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction. AB - We investigated whether admission estimated glomerular filtration rate (eGFR) values are associated with no-reflow phenomenon in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Patients (n = 673; 59 +/- 13 years; 77.1% men) were stratified into 3 groups according to eGFR at admission: normal renal function (eGFR >= 90 mL/min/1.73 m2), mild renal impairment (eGFR 60-89 mL/min/1.73 m2), and moderate renal impairment (eGFR 30-59 mL/min/1.73 m2). No-reflow phenomenon was defined as thrombolysis in myocardial infarction flow grade <3 after pPCI. The rate of no-reflow gradually increased from the normal renal function group to the moderate impaired renal function group (P < .001). Multivariate analysis showed that eGFR (odds ratio [OR] 0.942, P < .001), Killip >=2 class (OR 3.968, P = .008), left ventricular ejection fraction (OR 0.959, P = .034), and early patency of infarct vessel (OR 0.186, P < .001) were independent predictors of no reflow phenomenon. Mild to moderate renal impairment at admission is independently associated with no-reflow phenomenon after pPCI. PMID- 25124681 TI - The miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 domain controls neonatal metabolic adaptation. AB - In mammals, birth entails complex metabolic adjustments essential for neonatal survival. Using a mouse knockout model, we identify crucial biological roles for the miR-379/miR-410 cluster within the imprinted Dlk1-Dio3 region during this metabolic transition. The miR-379/miR-410 locus, also named C14MC in humans, is the largest known placental mammal-specific miRNA cluster, whose 39 miRNA genes are expressed only from the maternal allele. We found that heterozygote pups with a maternal--but not paternal--deletion of the miRNA cluster display partially penetrant neonatal lethality with defects in the maintenance of energy homeostasis. This maladaptive metabolic response is caused, at least in part, by profound changes in the activation of the neonatal hepatic gene expression program, pointing to as yet unidentified regulatory pathways that govern this crucial metabolic transition in the newborn's liver. Not only does our study highlight the physiological importance of miRNA genes that recently evolved in placental mammal lineages but it also unveils additional layers of RNA-mediated gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on metabolic control at birth and have likely contributed to mammal evolution. PMID- 25124683 TI - The effect of bupropion XL and escitalopram on memory and functional outcomes in adults with major depressive disorder: results from a randomized controlled trial. AB - Decrements in cognitive function are a common feature of Major Depressive Disorder (MDD), and whether distinct classes of antidepressants differentially affect memory in these individuals has not been sufficiently evaluated. In this study we sought to determine the effect of escitalopram and bupropion XL on memory and psychosocial function. Forty-one individuals (18-50 years) with MDD were enrolled in an 8-week, double-blind, double-dummy, randomized controlled comparative trial of bupropion XL and escitalopram. Thirty-six participants completed pre and post memory assessments. Verbal, non-verbal and working memory were evaluated with a comprehensive neuropsychological battery. Psychosocial function was assessed with the Sheehan Disability Scale and Endicott Work Productivity Scale. Escitalopram and bupropion XL significantly improved immediate as well as delayed verbal and nonverbal memory, global function (all p<=0.001), and work productivity (p=0.045), with no significant between-group differences. Improvement in immediate verbal memory exerted a direct influence on improvement in global function (p=0.006). Treatment with either escitalopram or bupropion XL was associated with improvement in memory and psychosocial function in adults with MDD. PMID- 25124684 TI - Daily life evidence of environment-incongruent emotion in schizophrenia. AB - Researchers have recently hypothesized that negative emotion in positive situations may be one mechanism for understanding emotion dysfunction in schizophrenia. Using ecological momentary assessment, we examined the relationship between emotion experience and environmental context in the daily lives of participants with and without schizophrenia. Participants with (n=47) and without schizophrenia (n=41) were provided a cellular telephone and called four times a day for one week. During each call participants rated their emotion experiences, described their current activities, and rated enjoyment from those activities. In line with previous research, participants with schizophrenia reported higher negative emotion overall relative to participants without schizophrenia, but equivalent levels of positive emotion and activity enjoyment. In line with the environment-incongruent negative emotion hypothesis, participants with schizophrenia evidenced a weaker relationship between reported enjoyment of current activities and current negative emotion compared to participants without schizophrenia. In addition, lower neurocognition predicted this weak relationship between negative emotion and context in the schizophrenia group. These findings provide ecologically valid support for environment incongruent negative emotion in schizophrenia, and suggest that people with schizophrenia with more impaired neurocognition may have more difficulties regulating negative emotion. PMID- 25124686 TI - Low PIAS3 expression in malignant mesothelioma is associated with increased STAT3 activation and poor patient survival. AB - PURPOSE: Deregulation of STAT3 activation is a hallmark of many cancer cells, and the underlying mechanisms are subject to intense investigation. We examined the extent of PIAS3 expression in mesothelioma cells and human tumor samples and determined the functional effects of PIAS3 expression on STAT3 signaling. EXPERIMENTAL DESIGN: We evaluated the expression of PIAS3 in mesothelioma tumors from patients and correlated the expression levels with the course of the disease. We also measured the effects of enhanced PIAS3 activity on STAT3 signaling, cellular growth, and viability in cultured mesothelioma cells. RESULTS: Gene expression databases revealed that mesotheliomas have the lowest levels of PIAS3 transcripts among solid tumors. PIAS3 expression in human mesothelioma tumors is significantly correlated with overall survival intervals (P = 0.058). The high expression of PIAS3 is predictive of a favorable prognosis and decreases the probability of death within one year after diagnosis by 44%. PIAS3 expression is functionally linked to STAT3 activation in mesothelioma cell lines. STAT3 downregulation with siRNA or enhanced expression of PIAS3 both inhibited mesothelioma cell growth and induced apoptosis. Mesothelioma cells are sensitive to curcumin and respond by the induction of PIAS3. Corroborative evidence has been obtained from STAT3 inhibition experiments. Exposure of the cells to a peptide derived from the PIAS3 protein that interferes with STAT3 function resulted in apoptosis induction and the inhibition of cell growth. CONCLUSION: These results suggest that PIAS3 protein expression impacts survival in patients with mesothelioma and that PIAS3 activation could become a therapeutic strategy. Clin Cancer Res; 20(19); 5124-32. (c)2014 AACR. PMID- 25124687 TI - Prolongation of overall survival in advanced lung adenocarcinoma patients with the XAGE1 (GAGED2a) antibody. AB - PURPOSE: The cancer/testis antigen XAGE1 (GAGED2a) is expressed in approximately 40% of advanced lung adenocarcinomas. We investigated the clinical relevance of the XAGE1 (GAGED2a) immune responses in patients with advanced lung adenocarcinoma. EXPERIMENTAL DESIGN: The XAGE1 (GAGED2a) antigen expression and EGFR mutation were determined with tumor tissues. The XAGE1 (GAGED2a) antibody and T-cell immune responses, as well as immune cell phenotypes, were analyzed with blood samples. Patients with EGFR wild-type (EGFRwt) tumors were treated with conventional platinum-based doublet chemotherapy and patients with EGFR mutated (EGFRmt) tumors were treated with EGFR-TKI and conventional chemotherapy. The overall survival (OS) rates of the antibody-positive and -negative patients were investigated. RESULTS: The results showed that the OS of antibody-positive patients was prolonged significantly compared with that of antibody-negative patients with either XAGE1 (GAGED2a) antigen-positive EGFRwt (31.5 vs. 15.6 months, P = 0.05) or EGFRmt (34.7 vs. 11.1 months, P = 0.001) tumors. Multivariate analysis showed that the presence of the XAGE1 (GAGED2a) antibody was a strong predictor for prolonged OS in patients with XAGE1 (GAGED2a) antigen positive tumors and in patients with either EGFRwt or EGFRmt tumors. On the other hand, XAGE1 (GAGED2a) antigen expression was a worse predictor in patients with EGFRmt tumors. Phenotypic and functional analyses of T cells indicated immune activation in the antibody-positive patients. CONCLUSIONS: The findings suggest that production of the XAGE1 (GAGED2a) antibody predicts good prognosis for patients with lung adenocarcinoma as an immune biomarker and the protective effect of this naturally occurring immune response supports the concept of immunotherapy. PMID- 25124685 TI - Clinical implications of phosphorylated STAT3 expression in De Novo diffuse large B-cell lymphoma. AB - PURPOSE: Activated signal transducer and activator of transcription 3 (STAT3) regulates tumor growth, invasion, cell proliferation, angiogenesis, immune response, and survival. Data regarding expression of phosphorylated (activated) STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of phosphorylated STAT3 (pSTAT3) on prognosis are limited. EXPERIMENTAL DESIGN: We evaluated expression of pSTAT3 in de novo DLBCL using immunohistochemistry, gene expression profiling (GEP), and gene set enrichment analysis (GSEA). Results were analyzed in correlation with cell-of-origin (COO), critical lymphoma biomarkers, and genetic translocations. RESULTS: pSTAT3 expression was observed in 16% of DLBCL and was associated with advanced stage, multiple extranodal sites of involvement, activated B-cell-like (ABC) subtype, MYC expression, and MYC/BCL2 expression. Expression of pSTAT3 predicted inferior overall survival (OS) and progression free survival (PFS) in patients with de novo DLBCL. When DLBCL cases were stratified according to COO or MYC expression, pSTAT3 expression did not predict inferior outcome, respectively. Multivariate analysis showed that the prognostic predictability of pSTAT3 expression was due to its association with the ABC subtype, MYC expression, and adverse clinical features. GEP demonstrated upregulation of genes, which can potentiate function of STAT3. GSEA showed the JAK-STAT pathway to be enriched in pSTAT3(+) DLBCL. CONCLUSIONS: The results of this study provide a rationale for the ongoing successful clinical trials targeting the JAK-STAT pathway in DLBCL. PMID- 25124689 TI - Matrix metalloproteinase (MMP)-2 and MMP-9 as inflammation markers of Trichinella spiralis and Trichinella pseudospiralis infections in mice. AB - Trichinella spiralis and Trichinella pseudospiralis exhibit differences in the host-parasite relationship such as the inflammatory response in parasitized muscles. Several studies indicate that matrix metalloproteinases (MMPs) represent a marker of inflammation since they regulate inflammation and immunity. The aim of this study was to evaluate the serum levels of gelatinases (MMP-9 and MMP-2) in mice experimentally infected with T. spiralis or T. pseudospiralis, to elucidate the involvement of these molecules during the inflammatory response to these parasites. Gelatin zymography on SDS polyacrilamide gels was used to assess the serum levels and in situ zymography on muscle histological sections to show the gelatinase-positive cells. In T. spiralis infected mice, the total MMP-9 serum level increased 6 days post-infection whereas, the total MMP-2 serum level increased onward. A similar trend was observed in T. pseudospiralis infected mice but the MMP-9 level was lower than that detected in T. spiralis infected mice. Significant differences were also observed in MMP-2 levels between the two experimental groups. The number of gelatinase positive cells was higher in T. spiralis than in T. pseudospiralis infected muscles. We conclude that MMP-9 and MMP-2 are markers of the inflammatory response for both T. spiralis and T. pseudospiralis infections. PMID- 25124688 TI - A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer. AB - PURPOSE: Epstein-Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumor antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses. EXPERIMENTAL DESIGN: Sixteen patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma (NPC) received three intradermal vaccinations of MVA-EL at 3-weekly intervals at dose levels between 5 * 10(7) and 5 * 10(8) plaque-forming units (pfu). Blood samples were taken at screening, after each vaccine cycle, and during the post vaccination period. T-cell responses were measured using IFNgamma ELISpot assays with overlapping EBNA1/LMP2 peptide mixes or HLA-matched epitope peptides. Polychromatic flow cytometry was used to characterize functionally responsive T cell populations. RESULTS: Vaccination was generally well tolerated. Immunity increased after vaccination to at least one antigen in 8 of 14 patients (7/14, EBNA1; 6/14, LMP2), including recognition of epitopes that vary between EBV strains associated with different ethnic groups. Immunophenotypic analysis revealed that vaccination induced differentiation and functional diversification of responsive T-cell populations specific for EBNA1 and LMP2 within the CD4 and CD8 compartments, respectively. CONCLUSIONS: MVA-EL is safe and immunogenic across diverse ethnicities and thus suitable for use in trials against different EBV-positive cancers globally as well as in South-East Asia where NPC is most common. The highest dose (5 * 10(8) pfu) is recommended for investigation in current phase IB and II trials. PMID- 25124690 TI - PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation. AB - Autophagosome formation is promoted by the PI3 kinase complex and negatively regulated by myotubularin phosphatases, indicating that regulation of local phosphatidylinositol 3-phosphate (PtdIns3P) levels is important for this early phase of autophagy. Here, we show that the Caenorhabditis elegans myotubularin phosphatase MTM-3 catalyzes PtdIns3P turnover late in autophagy. MTM-3 acts downstream of the ATG-2/EPG-6 complex and upstream of EPG-5 to promote autophagosome maturation into autolysosomes. MTM-3 is recruited to autophagosomes by PtdIns3P, and loss of MTM-3 causes increased autophagic association of ATG-18 in a PtdIns3P-dependent manner. Our data reveal critical roles of PtdIns3P turnover in autophagosome maturation and/or autolysosome formation. PMID- 25124691 TI - Identification of previously undiagnosed diabetes and prediabetes in the inpatient setting using risk factor and hemoglobin A1C screening. AB - BACKGROUND: Identifying diabetes early in its progression can present opportunities to intervene with education and medical management to prevent diabetes-related complications. OBJECTIVE: The primary objective was to determine the incidence of diabetes in hospitalized patients without insurance or routine outpatient care using recommendations by the American Diabetes Association (ADA) Standards of Medical Care in Diabetes for diabetes risk screening and diagnosis. METHODS: This study was conducted at a community hospital in Abilene, Texas. Hospitalized patients were screened if they had self-payer status and did not have a primary care physician. If patients met screening criteria based on risk factors listed in the ADA guidelines, a hemoglobin A1C test and fasting plasma glucose test were completed during hospitalization. Patients found to have diabetes were referred for outpatient education and management of diabetes. Data to determine the incidence of diabetes diagnosis were collected retrospectively. RESULTS: A total of 460 patients were screened for inclusion. Of the 92 patients included in the analysis, 8.7% (n=8) were identified as having diabetes and 39.1% (n=36) with prediabetes. Age and hypertension were independently positively correlated with increased risk for diabetes (P=0.002; P=0.045). CONCLUSIONS: Using risk factor screening based on ADA recommendations in the inpatient setting did not identify a significant number of patients with diabetes. This study found specific risk factors to be correlated with diagnosis of diabetes. Rather than using routine screening based on the number of risk factors, the presence of highly correlated risk factors may be an indication for diabetes screening. PMID- 25124692 TI - Long-term effectiveness of supported employment: 5-year follow-up of a randomized controlled trial. AB - OBJECTIVE: The individual placement and support model of supported employment has been shown to be more effective than other vocational approaches in improving competitive work over 1-2 years in persons with severe mental illness. The authors evaluated the longer-term effects of the model compared with traditional vocational rehabilitation over 5 years. METHOD: A randomized controlled trial compared supported employment to traditional vocational rehabilitation in 100 unemployed persons with severe mental illness. Competitive work and hospital admissions were tracked for 5 years, and interviews were conducted at 2 and 5 years to assess recovery attitudes and quality of life. A cost-benefit analysis compared program and total treatment costs to earnings from competitive employment. RESULTS: The beneficial effects of supported employment on work at 2 years were sustained over the 5-year follow-up period. Participants in supported employment were more likely to obtain competitive work than those in traditional vocational rehabilitation (65% compared with 33%), worked more hours and weeks, earned more wages, and had longer job tenures. Reliance on supported employment services for retaining competitive work decreased from 2 years to 5 years for participants in supported employment. Participants were also significantly less likely to be hospitalized, had fewer psychiatric hospital admissions, and spent fewer days in the hospital. The social return on investment was higher for supported employment participants, whether calculated as the ratio of work earnings to vocational program costs or of work earnings to total vocational program and mental health treatment costs. CONCLUSIONS: The results demonstrate that the greater effectiveness of supported employment in improving competitive work outcomes is sustained beyond 2 years and suggest that supported employment programs contribute to reduced hospitalizations and produce a higher social return on investment. PMID- 25124693 TI - Extranodal natural killer/T-cell lymphoma nasal type: detection by computed tomography features. AB - OBJECTIVES/HYPOTHESIS: Nasal natural killer/T-cell lymphoma (NKTL) often has an infiltrative pattern in computed tomography that makes them difficult to distinguish from benign inflammatory diseases. This study aimed to design a method of measuring the thickness of the nasal floor and nasal septum, determine the critical value of mucosal thickness that may implicate these NKTL cases from benign inflammatory disease, and finally make a complete flowchart to detect NKTL with minimal mistake. STUDY DESIGN: Thirty-two patients with nasal NKTL and 173 patients with severe chronic rhinosinusitis with or without polyposis were enrolled. The patients' data were collected retrospectively. METHODS: All patients underwent standard computed tomography of the paranasal sinuses. The coronal section near the vertical part of the ground lamina was chosen for measurement, and the thickest points along the nasal floor and septum were measured. RESULTS: Patients with NKTL had thicker nasal floors and/or septa than those with chronic rhinosinusitis, recurrent sinusitis, or pansinusitis (P < .001). If the cutoff points of the nasal floor and nasal septum thickness were set at 2.0 mm and 2.5 mm, respectively, the probability of being thicker than the corresponding points in the CRS group was <2%, and the possibility of other diagnoses should be considered. CONCLUSIONS: Nasal floor mucosal thickness >2.0 mm or nasal septum mucosal thickness >2.5 mm may be indicators serving as one of several important hints for implicit NKTL. Finally, we established a diagnostic flowchart to include all of these important hints. LEVEL OF EVIDENCE: 4. PMID- 25124694 TI - Dynamic behaviors of approximately ellipsoidal microbubbles photothermally generated by a graphene oxide-microheater. AB - Thermal microbubbles generally grow directly from the heater and are spherical to minimize surface tension. We demonstrate a novel type of microbubble indirectly generated from a graphene oxide-microheater. Graphene oxide's photothermal properties allowed for efficient generation of a thermal gradient field on the microscale. A series of approximately ellipsoidal microbubbles were generated on the smooth microwire based on heterogeneous nucleation. Other dynamic behaviors induced by the microheater such as constant growth, directional transport and coalescence were also investigated experimentally and theoretically. The results are not only helpful for understanding the bubble dynamics but also useful for developing novel photothermal bubble-based devices. PMID- 25124695 TI - Prevention of behavior problems in a selected population: Stepping stones triple P for parents of young children with disabilities. AB - Because young children with disabilities are at elevated risk for development of challenging behaviors, and caregivers of these children typically lack access to evidence-based parenting interventions, two randomized trials were conducted to examine the impact of an evidence-based parenting intervention, Stepping Stones Triple P (SSTP), as a selective preventive intervention. Both studies targeted parents of children under two with a variety of disabilities who were enrolled in the IDEA Part C Early Intervention (EI) system in one state. SSTP was delivered in family homes. In Study One, 49 families were randomly assigned to EI services as usual, with or without SSTP; a 52% attrition rate from treatment was seen. No significant between-group differences were seen aside from a trend toward reduced symptoms of parental depression at follow-up. Intervention group children demonstrated significant decline in behavior problems from post treatment to follow-up, and there was a trend toward improved parenting style in the intervention group during this same time frame. Study Two incorporated a separate workforce intervention for EI service coordinators; 40 families on their caseloads were then randomly assigned to receive EI services as usual with or without SSTP. Attrition from treatment was limited to 20%. No differential impact was seen on child behavior; a trend was noted post-treatment on parent symptoms of depression and on the observed parent-child relationship. At 12-month follow up, there was a trend favoring improvement in the intervention group in parenting style; statistically significant impact was also seen on the observed quality of the parent-child relationship. SSTP shows promise as a selective preventive intervention for an early intervention population. Reasons for the differential findings between the two studies are explored and suggestions for future research are provided. PMID- 25124696 TI - Recent insights into genotype-phenotype relationships in patients with Rett syndrome using a fine grain scale. AB - Mutations in MECP2 gene cause Rett syndrome (RTT), a neurodevelopmental disorder affecting around 1 in 10,000 female births. The clinical picture of RTT appears quite heterogeneous for each single feature. Mutations in MECP2 gene have been associated with the onset of RTT. The most known gene function consists of transcriptional repression of specific target genes, mainly by the binding of its methyl binding domain (MBD) to methylated CpG nucleotides and recruiting co repressors and histone deacetylase binding to DNA by its transcription repressor domain (TRD). This study aimed at evaluating a cohort of 114 Rett syndrome (RTT) patients with a detailed scale measuring the different kinds of impairments produced by the syndrome. The sample included relatively large subsets of the most frequent mutations, so that genotype-phenotype correlations could be tested. Results revealed that frequent missense mutations showed a specific profile in different areas of impairment. The R306C mutation, considered as producing mild impairment, was associated to a moderate phenotype in which behavioural characteristics were mainly affected. A notable difference emerged by comparing mutations truncating the protein before and after the nuclear localization signal; such a difference concerned prevalently the motor-functional and autonomy skills of the patients, affecting the management of everyday activities. PMID- 25124698 TI - Arithmetic strategy development and its domain-specific and domain-general cognitive correlates: a longitudinal study in children with persistent mathematical learning difficulties. AB - Deficits in arithmetic fact retrieval constitute the hallmark of children with mathematical learning difficulties (MLD). It remains, however, unclear which cognitive deficits underpin these difficulties in arithmetic fact retrieval. Many prior studies defined MLD by considering low achievement criteria and not by additionally taking the persistence of the MLD into account. Therefore, the present longitudinal study contrasted children with persistent MLD (MLD-p; mean age: 9 years 2 months) and typically developing (TD) children (mean age: 9 years 6 months) at three time points, to explore whether differences in arithmetic strategy development were associated with differences in numerical magnitude processing, working memory and phonological processing. Our longitudinal data revealed that children with MLD-p had persistent arithmetic fact retrieval deficits at each time point. Children with MLD-p showed persistent impairments in symbolic, but not in nonsymbolic, magnitude processing at each time point. The two groups differed in phonological processing, but not in working memory. Our data indicate that both domain-specific and domain-general cognitive abilities contribute to individual differences in children's arithmetic strategy development, and that the symbolic processing of numerical magnitudes might be a particular risk factor for children with MLD-p. PMID- 25124699 TI - To evaluate the effects of a simplified hand washing improvement program in schoolchildren with mild intellectual disability: a pilot study. AB - A quasi-experimental study using a pretest-posttest design with a control group was used to evaluate the effects of a simplified 5-step multimedia visualization hand hygiene improvement program by schoolchildren with mild intellectual disability (MID). A total of twenty schoolchildren aged 6-12 years old with MID (12 males) were recruited and they were assigned into intervention (n=10) and control (n=10) groups. To evaluate the quality of their hand washing, Glow gel, which contains plastic simulated germs that are visible under an ultra-violet lamp, was applied to participants' hands to assess the quality of hand washing by comparing the amount of visible Glow gel before and after hand washing using a 4 point scale. Four raters used this 4-point scale to assess the quality of hand washing through digital photo images of the participants' hands. A total of eight digital photos per participant were taken. A fifteen-minute hand washing training session was conducted every school day for 4 weeks for the intervention group. Those in the control group received no training. A multimedia visual package on steps of hand washing was presented together with a reward system, whereby a number of stars were earned each week depending on the quality of hand washing. Results showed encouraging findings, as the schoolchildren in the intervention group showed significant improvement in hand washing (p<0.001) and the improvement was stronger than that of the control group (p=0.02). To conclude, a systematic instruction emphasizing multimedia visualization in a hand washing improvement program can be successfully implemented in a special school, and the effect of integrating multimedia visuals in the hand hygiene program could improve hand hygiene among schoolchildren with MID. PMID- 25124697 TI - Metabolomic (anthropometric and biochemical) indexes and metabolic syndrome in adolescents and young adults with intellectual disabilities. AB - The aim of the present study was to describe the use of combination of international standardized anthropometric parameters, along with biochemical parameters (metabolomic indexes) to identify metabolic syndrome (MetS), in persons with intellectual disabilities. We conducted a cross-sectional study of 42 adolescents and young adults with intellectual disabilities (aged 13-30years) who attend special schools in Ciudad Juarez, Chihuahua, Mexico. The study included anthropometric (using the International Society for the Advancement of Kineanthropometry recommendations) and biochemical measures, and their combinations as metabolomic-indexes, that can significantly predict MetS occurrence in this vulnerable population. Waist circumference (WC) and relaxed arm circumference, both adjusted for height, have the highest correlation with MetS (R2=0.23-0.47, p<0.01). Besides body mass index (BMI) and WC we propose other indicators such as, skinfolds, hip circumference and relaxed arm circumference, all of them adjusted by height in order to better define the presence of MetS in persons with intellectual disabilities. PMID- 25124700 TI - A computer-aided program for helping patients with moderate Alzheimer's disease engage in verbal reminiscence. AB - This study assessed a simple computer-aided program for helping patients with moderate Alzheimer's disease engage in verbal reminiscence. In practice, the program was aimed at fostering the patient's verbal engagement on a number of life experiences/topics previously selected for him or her and introduced in the sessions through a friendly female, who appeared on the computer screen. The female asked the patient about the aforementioned experiences/topics, and provided him or her with positive attention, and possibly verbal guidance (i.e., prompts/encouragements). Eight patients were involved in the study, which was carried out according to non-concurrent multiple baseline designs across participants. Seven of them showed clear improvement during the intervention phase (i.e., with the program). Their mean percentages of intervals with verbal engagement/reminiscence ranged from close to zero to about 15 during the baseline and from above 50 to above 75 during the intervention. The results were discussed in relation to previous literature on reminiscence therapy, with specific emphasis on the need for (a) replication studies and (b) the development of new versions of the technology-aided program to improve its impact and reach a wider number of patients. PMID- 25124702 TI - Effects of 1,25-dihydroxyvitamin D3 on human epidermal melanocytes and melanoblasts. PMID- 25124701 TI - A pilot study of angiogenin in heart failure with preserved ejection fraction: a novel potential biomarker for diagnosis and prognosis? AB - Characteristics of heart failure with preserved ejection fraction (HFPEF) have not yet been fully understood. The objectives of this pilot study are to detect protein expression profile in the sera of HFPEF patients, and to identify potential biomarkers for the disease. Five hundred and seven proteins were detected in the sera of healthy volunteers and patients with either HFPEF or hypertension using antibody microarrays (three in each group). The results showed that the serum concentrations of 17 proteins (e.g. angiogenin, activin A and artemin) differed considerably between HFPEF and non-HFPEF patients (hypertensive patients and healthy controls), while a protein expression pattern distinct from that in non-HFPEF patients was associated with HFPEF patients. The up-regulation of angiogenin in both HFPEF patients with LVEF >=50% (P = 0.004) and a subset of HFPEF patients with LVEF = 41-49% (P < 0.001) was further validated in 16 HFPEF patients and 16 healthy controls. Meanwhile, angiogenin distinguished HFPEF patients from controls with a mean area under the receiver operating characteristic curve of 0.88 (P < 0.001) and a diagnostic cut-off point of 426 ng/ml. Moreover, the angiogenin levels in HFPEF patients were positively correlated with Lg(N-terminal pro-B-type natriuretic peptide, NT-proBNP) (P < 0.001). In addition, high angiogenin level (>=426 ng/ml) was a predictor of all cause death within a short-term follow-up duration, but not in the longer term of 36 months. This pilot study indicates that the aforementioned 17 potential biomarkers, such as angiogenin, may hold great promise for both diagnosis and prognosis assessment of HFPEF. PMID- 25124703 TI - Identification and characterization of human Rad51 inhibitors by screening of an existing drug library. AB - Homologous Recombination (HR) plays an essential role in cellular proliferation and in maintaining genomic stability by repairing DNA double-stranded breaks that appear during replication. Rad51, a key protein of HR in eukaryotes, can have an elevated expression level in tumor cells, which correlates with their resistance to anticancer therapies. Therefore, targeted inhibition of Rad51 through inhibitor may improve the tumor response to these therapies. In order to identify small molecules that inhibit Rad51 activity, we screened the Prestwick Library (1120 molecules) for their effect on the strand exchange reaction catalyzed by Rad51. We found that Chicago Sky Blue (CSB) is a potent inhibitor of Rad51, showing IC50 values in the low nanomolar range (400 nM). Biochemical analysis demonstrated that the inhibitory mechanism probably occurs by disrupting the Rad51 association with the single-stranded DNA, which prevents the nucleoprotein filament formation, the first step of the protein activity. Structure Activity Relationship analysis with a number of compounds that shared structure homology with CSB was also performed. The sensitivity of Rad51 inhibition to CSB modifications suggests specific interactions between the molecule and Rad51 nucleofilament. CSB and some of its analogs open up new perspectives in the search for agents capable of potentiating chemo- and radio-therapy treatments for cancer. Moreover, these compounds may be excellent tools to analyze Rad51 cellular functions. Our study also highlights how CSB and its analogs, which are frequently used in colorants, stains and markers, could be responsible of unwanted side effects by perturbing the DNA repair process. PMID- 25124705 TI - Local anesthetic versus forced coughing at colposcopic-guided biopsy: a prospective study. AB - OBJECTIVE: To evaluate whether the administration of local anesthetic (LA) reduces pain in comparison with forced coughing (FC) for the execution of colposcopically guided biopsies (CGBs). STUDY DESIGN: Data of 100 consecutive patients undergoing CGBs with the use of LA or FC were prospectively evaluated. Procedure-related pain was assessed with the use of a 100-mm visual analogue scale. RESULTS: Fifty-one and 49 patients had CGBs using LA and FC, respectively. No between-group differences were observed in terms of pain related to speculum insertion, CGBs and pain recorded after the procedures (p>0.05). However, patients in the LA group experienced pain related to cervical injection for administration of anesthesia (mean (+/-SD): 12.4 (+/-1.6)). Operative time was longer in the LA than in the FC group (7.2 (+/-0.2) vs. 5.0 (+/-0.1)min; p<0.001). CONCLUSIONS: FC should be preferred over LA. Although CGB-related pain levels do not differ, the omission of intracervical injection is associated with undoubted advantages. PMID- 25124706 TI - A review of stroke and pregnancy: incidence, management and prevention. AB - Stroke, defined as a focal or global disturbance of cerebral function lasting over 24h resulting from disruption of its blood supply, is a devastating event for a pregnant woman. This can result in long-term disability or death, and impact on her family and unborn child. In addition to pre-existing patient risk factors, the hypercoagulable state and pre-eclampsia need to be taken into account. The patterns and types of stroke affect pregnant women differ from the non-pregnant female population of child-bearing age. Like other thrombo-embolic diseases in pregnancy, stroke is essentially a disease of the puerperium. Population studies have estimated the risk of stroke at between 21.2 and 46.2 per 100,000. The US Nationwide Inpatient Sample, identified 2850 pregnancies complicated by stroke in the United States in 2000-2001, for a rate of 34.2 per 100,000 deliveries. There were 117 deaths, a mortality rate of 1.4 per 100,000. Both the mortality and disability rates were higher than previously reported, with 10-13% of women dying. With the increasing prevalence of obesity, hypertension and cardiac disease amongst women of child-bearing age, so is the incidence of stroke during pregnancy and the puerperium. In the United States, an alarming trend toward higher numbers of stroke hospitalizations during the last decade was demonstrated in studies from 1995 to 1996 and 2006 to 2007. The rate of all types of stroke increased by 47% among antenatal hospitalizations, and by 83% among post-partum hospitalizations. Hypertensive disorders, obesity and heart disease complicated 32% of antenatal admissions and 53% of post-partum admissions. In addition to pre-existing patient risk factors, the hypercoagulable state and pre-eclampsia need to be taken into account. The patterns and types of stroke affect pregnant women differ from the non-pregnant female population of child-bearing age. Like other thrombo-embolic diseases in pregnancy, stroke is essentially a disease of the puerperium. PMID- 25124707 TI - The influence of prolonged preterm premature rupture of the membranes on neonatal outcome of the presenting and non-presenting twin. AB - OBJECTIVE: To compare the neonatal outcome in twin gestations complicated by prolonged preterm premature rupture of membranes (PPROM). STUDY DESIGN: Between the years 2000 and 2010 we identified 48 women with twin pregnancies who were diagnosed as having PPROM and a latency period to delivery >24h. We compared the neonatal morbidity and mortality between the presenting and non-presenting twins, assuming that the rupture occurred in the lower sac. Importantly, in 30 women we were able to identify the location of the ruptured sac by ultrasound examination demonstrating oligohydramnion. In these 30 cases, neonatal outcome of fetuses in the ruptured sac and those in the intact sac were compared. RESULTS: The median gestational age was 31 weeks (range 28-33) with a median latency period between PPROM and delivery of 9 days (range 1-18). Of the identified ruptures 90% (27/30) occurred in the lower sac (presenting twin). There was no significant difference between the presenting and non-presenting twin in terms of neonatal morbidity and mortality. Moreover, no difference was found when fetuses with ruptured sac were compared to those with intact membrane sac. Importantly, the outcomes were not affected by the length of the latency period. CONCLUSION: The current study results demonstrated that the outcome of fetuses exposed to prolonged preterm rupture of membranes is similar to that of fetuses with intact membranes. Our data suggest that rupture of membranes per se did not cause any deleterious clinical manifestations or lead to clinical discordant inflammation and poor neonatal outcome, supporting a conservative management of twin pregnancies with PPROM. PMID- 25124708 TI - Vitamin C attenuates detrimental effects of diabetes mellitus on sperm parameters, chromatin quality and rate of apoptosis in mice. AB - OBJECTIVES: The main goal was to examine the protective effects of vitamin C on sperm parameters, sperm chromatin condensation and apoptosis in experimentally induced diabetic mice. STUDY DESIGN: 28 adult Syrian mice were divided into 4 groups. In Group1, the mice were diabetic that received a single dose of Streptozocin (STZ) (200mg/kg) intra-peritoneally (ip). Group 2 was included diabetic mice that received vitamin C (10mg/kg/daily, ip). Mice in group 3 were received vitamin C and group 4 was considered as control. After 35 days, sperm analysis was done accordingly. To asses sperm chromatin and DNA quality, we used aniline blue (AB), toluidine blue (TB), chromomycin A3 (CMA3), acridine orange (AO) and terminal transferase mediated deoxyuridine triphosphate biotin end labeling (TUNEL) tests. RESULTS: All of the sperm parameters (count, motility, morphology and viability) had significant reduction in diabetic mice but, the data showed a significant increase in all of the sperm parameters in diabetic+vitamin C when compared with diabetic and control animals (P<0.05). There were significant differences (P<0.001) between groups regarding to TB staining (48.8+/-5.92 vs 34.3+/-4.13), AO test (35.9+/-6.11 vs 20.8+/-2.89) and TUNEL test (39.42+/-7.18 vs 22.00+/-3.65) in diabetic and diabetic+vitamin C groups, respectively. Nevertheless, in CMA3 and AB staining assays, there were not any significant differences between different groups. CONCLUSION: Vitamin C, as a potent antioxidant, can attenuate detrimental effects of diabetes mellitus on the sperm parameters, chromatin quality and apoptosis in an experimental model. PMID- 25124704 TI - Novel third-generation water-soluble noscapine analogs as superior microtubule interfering agents with enhanced antiproliferative activity. AB - Noscapine, an opium-derived 'kinder-gentler' microtubule-modulating drug is in Phase I/II clinical trials for cancer chemotherapy. However, its limited water solubility encumbers its development into an oral anticancer drug with clinical promise. Here we report the synthesis of 9 third-generation, water-soluble noscapine analogs with negatively charged sulfonato and positively charged quaternary ammonium groups using noscapine, 9-bromonoscapine and 9-aminonoscapine as scaffolds. The predictive free energy of solvation was found to be lower for sulfonates (6a-c; 8a-c) compared to the quaternary ammonium-substituted counterparts, explaining their higher water solubility. In addition, sulfonates showed higher charge dispersability, which may effectively shield the hydrophobicity of isoquinoline nucleus as indicated by hydrophobicity mapping methods. These in silico data underscore efficient net charge balancing, which may explain higher water solubility and thus enhanced antiproliferative efficacy and improved bioavailability. We observed that 6b, 8b and 8c strongly inhibited tubulin polymerization and demonstrated significant antiproliferative activity against four cancer cell lines compared to noscapine. Molecular simulation and docking studies of tubulin-drug complexes revealed that the brominated compound with a four-carbon chain (4b, 6b, and 8b) showed optimal binding with tubulin heterodimers. Interestingly, 6b, 8b and 8c treated PC-3 cells resulted in preponderance of mitotic cells with multipolar spindle morphology, suggesting that they stall the cell cycle. Furthermore, in vivo pharmacokinetic evaluation of 6b, 8b and 8c revealed at least 1-2-fold improvement in their bioavailability compared to noscapine. To our knowledge, this is the first report to demonstrate novel water-soluble noscapine analogs that may pave the way for future pre clinical drug development. PMID- 25124709 TI - Toxoplasma gondii and anxiety disorders in a community-based sample. AB - A growing body of literature suggests that exposure to the neurotropic parasite Toxoplasma gondii (T. gondii) is associated with increased risk of mental disorders, particularly schizophrenia. However, a potential association between T. gondii exposure and anxiety disorders has not been rigorously explored. Here, we examine the association of T. gondii infection with both anxiety and mood disorders. Participants (n=484) were drawn from the Detroit Neighborhood Health Study, a population-representative sample of Detroit residents. Logistic regression was used to examine the associations between T. gondii exposure (defined by seropositivity and IgG antibody levels) and three mental disorders: generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD) and depression. We found that T. gondii seropositivity was associated with a 2 times greater odds of GAD (odds ratio (OR), 2.25; 95% confidence interval (CI), 1.11 4.53) after adjusting for age, gender, race, income, marital status, and medication. Individuals in the highest antibody level category had more than 3 times higher odds of GAD (OR, 3.35; 95% CI, 1.41-7.97). Neither T. gondii seropositivity nor IgG antibody levels was significantly associated with PTSD or depression. Our findings indicate that T. gondii infection is strongly and significantly associated with GAD. While prospective confirmation is needed, T. gondii infection may play a role in the development of GAD. PMID- 25124710 TI - A role for inflammatory metabolites as modulators of the glutamate N-methyl-D aspartate receptor in depression and suicidality. AB - BACKGROUND: Patients with depression and suicidality suffer from low-grade neuroinflammation. Pro-inflammatory cytokines activate indoleamine 2,3 dioxygenase, an initial enzyme of the kynurenine pathway. This pathway produces neuroactive metabolites, including quinolinic- and kynurenic acid, binding to the glutamate N-methyl-d-aspartate-receptor, which is hypothesized to be part of the neural mechanisms underlying symptoms of depression. We therefore hypothesized that symptoms of depression and suicidality would fluctuate over time in patients prone to suicidal behavior, depending on the degree of inflammation and kynurenine metabolite levels in the cerebrospinal fluid (CSF). METHODS: We measured cytokines and kynurenine metabolites in CSF, collected from suicide attempters at repeated occasions over 2 years (total patient samples n=143, individuals n=30) and healthy controls (n=36). The association between the markers and psychiatric symptoms was assessed using the Montgomery Asberg Depression Rating Scale and the Suicide Assessment Scale. RESULTS: Quinolinic acid was increased and kynurenic acid decreased over time in suicidal patients versus healthy controls. Furthermore, we found a significant association between low kynurenic acid and severe depressive symptoms, as well as between high interleukin-6 levels and more severe suicidal symptoms. CONCLUSIONS: We demonstrate a long-term dysregulation of the kynurenine pathway in the central nervous system of suicide attempters. An increased load of inflammatory cytokines was coupled to more severe symptoms. We therefore suggest that patients with a dysregulated kynurenine pathway are vulnerable to develop depressive symptoms upon inflammatory conditions, as a result the excess production of the NMDA receptor agonist quinolinic acid. This study provides a neurobiological framework supporting the use of NMDA-receptor antagonists in the treatment of suicidality and depression. PMID- 25124711 TI - Explaining person identification: an inquiry into the tracking of human agents. AB - To introduce the issue of the tracking and identification of human agents, I examine the ability of an agent ("a tracker") to track a human person ("a target") and distinguish this target from other individuals: The ability to perform person identification. First, I discuss influential mechanistic models of the perceptual recognition of human faces and people (the face-recognition program). Such models propose detailed hypotheses about the parts and activities of the mental mechanisms that control the perceptual recognition of persons. However, models based on perceptual recognition are incomplete theories of person identification because they do not explain several identification behaviors that are fundamental to human social interactions (e.g., identifying unobservable persons and imposters). Furthermore, recognition-based models tend to appeal to the controversial concept of the "identity" of a person without explaining what determines personal identity and persistence. To overcome these limitations, I propose to integrate the face-recognition program into a broader causal historical theory of identification. The causal-historical theory of identification complements models focused on perceptual recognition because it can account for the types of non-perceptual identification overlooked by the face recognition program. Moreover, it can decompose the identification behaviors into tracking processes that succeed or fail to be sensitive to causal characteristics of a target. I illustrate these advantages with a discussion of the difference between the tracking of a person understood as either a causally continuous biological organism (organism-based tracking) or a psychologically continuous mind (psychological tracking). Finally, I argue that the causal-historical theory provides a theoretical framework for investigating the tracking of relations between a target and its contextual and historical attributes, such as a target's possessions. PMID- 25124712 TI - Self medicated antibiotics in Bangladesh: a cross-sectional health survey conducted in the Rajshahi City. AB - BACKGROUND: Antibiotic self medication is highly prevalent in the developing countries due to easy availability and poor regulatory controls for selling these drugs. The purpose of this study was to evaluate the prevalence of self medication with antibiotics for the treatment of various diseases by the peoples of Rajshahi city in Bangladesh. METHODS: A cross-sectional survey was conducted to the patient's (n = 1300) at eight locations of Rajshahi city in Bangladesh from March to April, 2014. The locations were selected by convenience and the study population within each study area was randomly selected. The survey was self-administered and included questions pertaining to self medicated drugs and antibiotic usage patterns as well. Data were analyzed using descriptive statistics. RESULTS: It was found that 347 (26.69%) out of 1300 participants experienced self medication with antibiotics. Over fifty percent of the patients studied were between the ages of 21-30 years with 83.57% of them being males and 16.43% females. The highest percentage of self medicated antibiotics was metronidazole (50.43%) followed by azithromycin (20.75%), ciprofloxacin (11.53%), amoxicillin (10.37%) and tetracycline (7.49%) respectively. The key reasons for the self medication of antibiotics was the pre-experience (45.82%), suggestions from others (28.24%) and knowledgeable of the antibiotics (16.14%). The perceived symptoms to purchase the antibiotics independently was dysentery, diarrhea and food poisoning (36.02%), cold, cough and fever (28.24%), infection (12.97%), dental carries and toothache (9.22%), irritable bowel syndrome (3.46%), acne (4.32%), ear and throat pain (2.31%). The duration of maximum antibiotics usage was ranges between 0-10 years. Only 4.32% patient's used self medicated antibiotics longer than 10 years. The patient's compliance for self medication of antibiotics varies from excellent to no comments whereas only 6.92% patients reported side effects for the self medication of antibiotics. CONCLUSIONS: The results of this study confirm that antibiotic self-medication is a relatively frequent problem in Bangladesh. Drug Administration of Bangladesh should implement the regulatory controls immediately on the distribution and selling of antibiotics in order to reduce the frequency of antibiotic misuse. PMID- 25124713 TI - Non-eosinophilic airway hyper-reactivity in mice, induced by IFN-gamma producing CD4(+) and CD8(+) lung T cells, is responsive to steroid treatment. AB - Non-eosinophilic asthma is characterized by infiltration of neutrophils into the lung and variable responsiveness to glucocorticoids. The pathophysiological mechanisms have not been characterized in detail. Here, we present an experimental asthma model in mice associated with non-eosinophilic airway inflammation and airway hyper-responsiveness (AHR). For this, BALB/c mice were sensitized by biolistic DNA immunization with a plasmid encoding the model antigen beta-galactosidase (pFascin-betaGal mice). For comparison, eosinophilic airway inflammation was induced by subcutaneous injection of betaGal protein (betaGal mice). Intranasal challenge of mice in both groups induced AHR to a comparable extent as well as recruitment of inflammatory cells into the airways. In contrast to betaGal mice, which exhibited extensive eosinophilic infiltration in the lung, goblet cell hyperplasia and polarization of CD4(+) T cells into Th2 and Th17 cells, pFascin-betaGal mice showed considerable neutrophilia, but no goblet cell hyperplasia and a predominance of Th1 and Tc1 cells in the airways. Depletion studies in pFascin-betaGal mice revealed that CD4(+) and CD8(+) cells cooperated to induce maximum inflammation, but that neutrophilic infiltration was not a prerequisite for AHR induction. Treatment of pFascin-betaGal mice with dexamethasone before intranasal challenge did not affect neutrophilic infiltration, but significantly reduced AHR, infiltration of monocytes and lymphocytes as well as content of IFN-gamma in the bronchoalveolar fluid. Our results suggest that non-eosinophilic asthma associated predominantly with Th1/Tc1 cells is susceptible to glucocorticoid treatment. pFascin-betaGal mice might represent a mouse model to study pathophysiological mechanisms proceeding in the subgroup of asthmatics with non-eosinophilic asthma that respond to inhaled steroids. PMID- 25124715 TI - Structure and development of 'witches' broom' galls in reproductive organs of Byrsonima sericea (Malpighiaceae) and their effects on host plants. AB - Galls are anomalies in plant development of parasitic origin that affect the cellular differentiation or growth and represent a remarkable plant-parasite interaction. Byrsonima sericea DC. (Malpighiaceae) is a super host of several different types of gall in both vegetative and reproductive organs. The existence of galls in reproductive organs and their effects on the host plant are seldom described in the literature. In this paper, we present a novel study of galls in plants of the Neotropical region: the 'witches' broom' galls developed in floral structures of B. sericea. The unaffected inflorescences are characterised by a single indeterminate main axis with spirally arranged flower buds. The flower buds developed five unaffected brownish hairy sepals and five pairs of elliptical yellow elaiophores, five yellow fringed petals, 10 stamens and a pistil with superior tricarpellar and trilocular ovary. The affected inflorescences showed changes in architecture, with branches arising from the main axis and flower buds. The flower buds exhibited several morphological and anatomical changes. The sepals, petals and carpels converted into leaf-like structures after differentiation. Stamens exhibited degeneration of the sporogenous tissue and structures containing hyphae and spores. The gynoecium did not develop, forming a central meristematic region, from which emerges the new inflorescence. In this work, we discuss the several changes in development of reproductive structures caused by witches' broom galls and their effects on reproductive success of the host plants. PMID- 25124714 TI - ADAM10 correlates with uveal melanoma metastasis and promotes in vitro invasion. AB - Uveal melanoma (UM) is a rare ocular tumor that may lead to deadly metastases in 50% of patients. A disintegrin and metalloproteinase (ADAM)10, ADAM17, and the HGF-receptor c-Met support invasiveness in different tumors. Here, we report that high ADAM10, MET, and, to a lesser extent, ADAM17 gene expression correlates with poor progression-free survival in UM patients (hazard ratio 2.7, 2.6, and 1.9, respectively). About 60% of primary UM expresses c-Met and/or ADAM10 proteins. Four UM cell lines display high levels of ADAM10 and ADAM17, which constitutively cleave c-Met, inducing the release of soluble c-Met. ADAM10/17 pharmacological inhibition or gene silencing reduces c-Met shedding, but has limited impact on surface c-Met, which is overexpressed. Importantly, ADAM10 silencing inhibits UM cell invasion driven by FCS or HGF, while ADAM17 silencing has a limited effect. Altogether our data indicate that ADAM10 has a pro-invasive role and may contribute to UM progression. PMID- 25124716 TI - Induced self-assembly of platinum(II) alkynyl complexes through specific interactions between citrate and guanidinium for proof-of-principle detection of citrate and an assay of citrate lyase. AB - Water-soluble alkynylplatinum(II) terpyridine complexes appended with guanidinium moieties, [Pt(tpy)(C=C-Ar)][OTf]2 (tpy=terpyridine; OTf=trifluoromethanesulfonate; Ar=C6 H4-{NHC(=NH2(+))(NH2)}-4 (1), C6 H4-{CH2 NHC(=NH2(+))(NH2)}-4 (2)), and [Pt(tBu3 tpy)(C=CC6H4-{NHC(=NH2(+))(NH2)} 4)][OTf]2 (3; tBu3 tpy=4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine), have been synthesized and characterized. The photophysical properties of the complexes have been studied. Based on the results of UV/Vis absorption, resonance light scattering, and dynamic light scattering experiments, in aqueous buffer solutions complexes 1 and 2 undergo aggregation in the presence of citrate through strong and specific electrostatic and hydrogen-bonding interactions with citrate. The emergence of a triplet metal-metal-to-ligand charge transfer ((3 MMLCT) emission in the near-infrared (NIR) region brought on by the induced self-assembly of complex 1 has been demonstrated for proof-of-principle detection of citrate with good sensitivity and selectivity over other mono- and dicarboxylate substrates in the tricarboxylic acid (TCA) cycle as well as phosphate and lactate anions. Such a good selectivity toward citrate has been rationalized by the high charge density of citrate under physiological conditions and specific interactions between the guanidinium moiety on complex 1 and citrate. Extension of the work to citrate detection in fetal bovine serum and real-time monitoring of the activity of citrate lyase by the NIR emission of complex 1 have also been demonstrated. PMID- 25124717 TI - The cross-sectional area changes in digital flexor tendons and suspensory ligament in foals by ultrasonographic examination. AB - REASONS FOR PERFORMING STUDY: Flexural deformities are common conditions of growing horses and are suggested to have a relationship with the contraction of musculotendinous units. However, limited studies have documented the changes in each tendon and ligament in the metacarpal region with age. OBJECTIVES: To investigate the changes in the cross-sectional area (CSA) of each tendon and ligament in the metacarpal region with age by ultrasonographic examination. STUDY DESIGN: Longitudinal study of foals from Day 1 to age 24 months. METHODS: The CSA of the superficial digital flexor tendon, deep digital flexor tendon, accessory ligament of the deep digital flexor tendon and suspensory ligament was measured by ultrasonographic examination at monthly intervals from Day 1 to age 24 months in 7 Thoroughbred foals. RESULTS: Changes in superficial digital flexor CSA in all regions were larger than those of other structures from 10 months to 15 months. The suspensory ligament CSA was significantly larger than those of other structures on Day 1 in both the region of suspensory origin (RSO) and region of suspensory body (RSBO). This condition continued until 2 months in the RSO and until 5 months in the RSBO. The changes in deep digital flexor CSA were larger than those of other structures from 2 to 5 months in both the RSO and RSBO. CONCLUSIONS: The rate of change in each structure varies with age. Thus, the functional adaptation with age that takes place may differ among structures because the primary function of each structure differs. PMID- 25124719 TI - Insights into the influence of dispersion correction in the theoretical treatment of guanidine-quinoline copper(I) complexes. AB - For the description of steric effects, dispersion correction is important in density functional theory. By investigation of sterically encumbered guanidine quinoline copper bis(chelate) complexes, we could show that the correct description requires modern dispersion correction using Becke-Johnson (BJ) damping and that earlier dispersion corrections are not sufficient. The triple zeta basis set def2-TZVP of the Ahlrichs series is balanced and converged for the structural description. With regard to functionals, the best structural description is obtained with the TPSSh functional but B3LYP is very suited as well. Cutting of ligand substituents leads to distortions which limit the predictive ability of such calculations. We recommend the calculation of "full" chemical systems with inclusion of dispersion correction using BJ damping. In the further analysis of the regarded copper bis(chelate) complexes, we found that the theoretical description of optical and Raman spectra is not much affected by the dispersion although charge transfer excitations come into play and that B3LYP/def2-TZVP is the best choice. Hence, we can derive the result that the correct structural description with dispersion serves as crucial basis for subsequent calculation steps. PMID- 25124720 TI - Combined semilunar valve stenoses in neonates: management approaches and literature review. AB - Combination of right and left ventricular outflow tracts obstruction is extremely rare. Neonates with combined aortic stenosis (AS) and pulmonary stenosis (PS) present in critical condition and required urgent treatment. The management approach is not well defined. We report five female neonates with combined AS and PS presented to our institute in the last 5 years, age (1-18 days), weight (2.2 3.4 kg). Two had associated muscular ventricular septal defects. The mean Doppler gradient across the aortic valve (AV) was 73 mmHg (53-105 mmHg) and across the pulmonary valve was 62 mmHg (44-76 mmHg). Three had balloon dilatation and one surgical repair. The fifth patient was managed conservatively, but had sudden cardiac death at age of 3 months. One patient arrived in shock and sepsis, underwent emergency balloon dilation of the AV in the ICU. Despite decreasing the gradient, she died next day after the procedure. The surviving children were well at median follow-up age of 3.4 years. This is an extremely rare combination which needs early intervention. The management approach is not well defined. Interventional catheterization is possibly the better option. PMID- 25124718 TI - Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility. AB - BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization. PMID- 25124721 TI - Cumulative radiation exposure in pediatric patients with congenital heart disease. AB - Certain pediatric patients undergoing surgery for the most severe forms of congenital heart disease are exposed to high doses of ionizing radiation. The amount of cumulative radiation exposure from all modalities has not yet been evaluated. The purpose of our study was to evaluate the cumulative radiation exposure in a contemporary cohort of patients with congenital heart disease undergoing single-ventricle palliation. This is a single-center, retrospective study of pediatric patients undergoing Fontan completion between May 2005 and May 2010. Radiation exposure from all procedures including cardiac catheterizations, computed tomography (CT) scans, plain film radiography, and nuclear medicine scans was evaluated. Radiation dose was calculated as the dose area product (MUGy m(2)) and was measured in all cardiac catheterizations, CT scans, and other imaging modalities. Seventy patients who underwent Fontan completion at a mean age of 3.6 +/- 1.5 years (range 1.4-8 years) were included in the study. Mean number of chest X-rays was 32 +/- 8 (range 10-285) with a mean cumulative total exposure of 1,320 MUGy m(2) (range 480-12,960) per patient. Mean number of cardiac catheterizations was 2.45 +/- 1.3 (range 1-8), and mean fluoroscopy and cine angiography exposures per case were 1,103 +/- 245 and 1,412 +/- 273 MUGy m(2) giving a mean cumulative exposure of 9,054 MUGy m(2) (range 2,515-201,200) per patient for all catheterizations. Mean number of CT scans performed was 0.44 +/- 0.4 (0-11), and the mean exposure was 352 MUGy m(2), giving a mean cumulative total of 154 MUGy m(2) (range 0-3,872) per person. A total of five lung perfusion scans were carried out. Radiation exposure in patients with congenital heart disease undergoing single-ventricle palliation is quite variable. Most of the exposure to ionizing radiation occurs during cardiac catheterization. Strategies to utilize other imaging modalities such as MRI would decrease exposure in this particular group of patients who may be particularly vulnerable to its side effects. PMID- 25124722 TI - Synthesis of pyridazinones through the copper(I)-catalyzed multicomponent reaction of aldehydes, hydrazines, and alkynylesters. AB - The copper-catalyzed multicomponent cyclization reaction, which combined aldehydes, hydrazines, and alkynylesters, was applied in the synthesis of pyridazinones. The reaction was regioselective and gave only six-membered pyridazinones in the complete absence of five-membered pyrazoles or a regioisomeric mixture. During this investigation, the use of 2-halobenzaldehyde as the starting material, under identical reaction conditions, gave 6-(2 ethoxyphenyl)pyridazinones after sequential Michael addition/1,2-addition/Ullmann cross-coupling reactions. PMID- 25124723 TI - SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients. AB - Methotrexate (MTX) is used for rheumatoid arthritis (RA) treatment showing a wide toxicity profile. This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) in genes encoding for MTX transporters with the occurrence of MTX-related toxicity (overall and gastrointestinal). A total of 233 Portuguese RA patients were genotyped for 23 SNPs. Haplotype analyses were performed and a toxicogenetic risk index (TRI) was created for SNPs that revealed to be statistically significant. Regarding MTX overall toxicity, an increased risk was associated to SLC19A1 rs7499 G carriers (p = 0.017), SLC46A1 rs2239907 GG (p = 0.030) and, SLCO1B1 rs4149056 T carriers (p = 0.040) and TT (p = 0.019). TRI revealed that patients with Index 3 were 18-fold more likely to present an adverse drug reaction when compared to those with Index 1 (p = 0.001). For MTX gastrointestinal toxicity, results demonstrated an increased risk associated with SLC19A1 rs7499 G carriers (p = 0.012) and GG (p = 0.045), SLC19A1 rs1051266 G carriers (p = 0.034), SLC19A1 rs2838956 A carriers (p = 0.049) and, SLCO1B1 rs4149056 T carriers (p = 0.042) and TT (p = 0.025). Haplotype analyses showed association between GGAG haplotype for SLC19A1 rs7499, rs1051266, rs2838956 and rs3788200 with MTX gastrointestinal toxicity (p = 0.029). TRI revealed that patients with Index 4 were 9-fold more likely to present a gastrointestinal disorder when compared to those with Index 1 (p = 0.020). This study demonstrated that SLC19A1, SLC46A1 and SLCO1B1 genotypes may help to identify patients with increased risk of MTX-related overall toxicity and that SLC19A1 and SLCO1B1 genotypes, and SLC19A1 haplotypes may help to identify patients with increased risk of MTX-related gastrointestinal toxicity. PMID- 25124725 TI - The BSD2 ortholog in Chlamydomonas reinhardtii is a polysome-associated chaperone that co-migrates on sucrose gradients with the rbcL transcript encoding the Rubisco large subunit. AB - The expression of the CO2 -fixation enzyme ribulose-bisphosphate carboxylase/oxygenase (Rubisco), which is affected by light, involves the cysteine-rich protein bundle-sheath defective-2 (BSD2) that was originally identified in maize bundle-sheath cells. We identified the BSD2 ortholog in Chlamydomonas reinhardtii as a small protein (17 kDa) localized to the chloroplast. The algal BSD2-ortholog contains four CXXCXGXG DnaJ-like elements, but lacks the other conserved domains of DnaJ. BSD2 co-migrated with the rbcL transcript on heavy polysomes, and both BSD2 and rbcL mRNA shifted to the lighter fractions under oxidizing conditions that repress the translation of the Rubisco large subunit (RbcL). This profile of co-migration supports the possibility that BSD2 is required for the de novo synthesis of RbcL. Furthermore, BSD2 co-migrated with the rbcL transcript in a C. reinhardtii premature-termination mutant that encodes the first 60 amino acids of RbcL. In both strains, BSD2 shared its migration profile with the rbcL transcript but not with psbA mRNA. The chaperone activity of BSD2 was exemplified by its ability to prevent the aggregation of both citrate synthase (CS) and RbcL in vitro following their chemical denaturation. This activity did not depend on the presence of the thiol groups on BSD2. In contrast, the activity of BSD2 in preventing the precipitation of reduced beta-chains in vitro in the insulin turbidity assay was thiol-dependent. We conclude that BSD2 combines a chaperone 'holdase' function with the ability to interact with free thiols, with both activities being required to protect newly synthesized RbcL chains. PMID- 25124727 TI - Cavity-induced microstreaming for simultaneous on-chip pumping and size-based separation of cells and particles. AB - We present a microfluidic platform for simultaneous on-chip pumping and size based separation of cells and particles without external fluidic control systems required for most existing platforms. The device utilizes an array of acoustically actuated air/liquid interfaces generated using dead-end side channels termed Lateral Cavity Acoustic Transducers (LCATs). The oscillating interfaces generate local streaming flow while the angle of the LCATs relative to the main channel generates a global bulk flow from the inlet to the outlet. The interaction of these two competing velocity fields (i.e. global bulk velocity vs. local streaming velocity) is responsible for the observed separation. It is shown that the separation of 5 MUm and 10 MUm polystyrene beads is dependent on the ratio of these two competing velocity fields. The experimental and simulation results suggest that particle trajectories based only on Stokes drag force cannot fully explain the separation behavior and that the impact of additional forces due to the oscillating flow field must be considered to determine the trajectory of the beads and ultimately the separation behavior of the device. To demonstrate an application of this separation platform with cellular components, smaller red blood cells (7.5 +/- 0.8 MUm) are separated from larger K562 cells (16.3 +/- 2.0 MUm) with viabilities comparable to those of controls based on a trypan blue exclusion assay. PMID- 25124724 TI - Autoantibodies associated with prenatal and childhood exposure to environmental chemicals in Faroese children. AB - Methylmercury, polychlorinated biphenyls (PCBs), and perfluorinated compounds (PFCs) are ubiquitous and persistent environmental chemicals with known or suspected toxic effects on the nervous system and the immune system. Animal studies have shown that tissue damage can elicit production of autoantibodies. However, it is not known if autoantibodies similarly will be generated and detectable in humans following toxicant exposures. Therefore, we conducted a pilot study to investigate if autoantibodies specific for neural and non-neural antigens could be detected in children at age 7 years who have been exposed to environmental chemicals. Both prenatal and age-7 exposures to mercury, PCBs, and PFCs were measured in 38 children in the Faroe Islands who were exposed to widely different levels of these chemicals due to their seafood-based diet. Concentrations of IgM and IgG autoantibodies specific to both neural (neurofilaments, cholineacetyltransferase, astrocyte glial fibrillary acidic protein, and myelin basic protein) and non-neural (actin, desmin, and keratin) antigens were measured and the associations of these autoantibody concentrations with chemical exposures were assessed using linear regression. Age-7 blood mercury concentrations were positively associated with titers of multiple neural- and non-neural-specific antibodies, mostly of the IgM isotype. Additionally, prenatal blood-mercury and -PCBs were negatively associated with anti-keratin IgG and prenatal PFOS was negatively associated with anti-actin IgG. These exploratory findings demonstrate that autoantibodies can be detected in the peripheral blood following exposure to environmental chemicals. The unexpected association of exposures with antibodies specific for non-neural antigens suggests that these chemicals may have toxicities that have not yet been recognized. PMID- 25124726 TI - Molecular characterization of SjBIRP, another apoptosis inhibitor, from Schistosoma japonicum. AB - Inhibitor of apoptosis proteins (IAP) play an important role in the regulation of apoptotic processes and are defined by the presence of baculoviral IAP repeat (BIR) domains. Here, we characterized a cDNA fragment (SjBIRP) synthesized from the RNA of Schistosoma japonicum, which was found to contain the BIR domain, suggesting that it could encode a potential IAP. Real-time PCR analyses indicated that SjBIRP transcription was detected at several stages of the schistosome's lifecycle, with increased levels present in schistosomula (7 days). In addition, the SjBIRP was highly expressed in adult females as compared to adult males. A functional assay showed that SjBIRP could inhibit caspase3/7 activity in both HeLa cells and schistosome lysates. Furthermore, SjBIRP expression profiles varied between different hosts of S. japonicum. Taken together, our preliminary studies suggest that SjBIRP may play a functional role in the regulation of apoptosis in schistosomes, and that it could be a potential drug target for schistosomiasis control. PMID- 25124728 TI - Modeling large-scale dynamic processes in the cell: polarization, waves, and division. AB - The past decade has witnessed significant developments in molecular biology techniques, fluorescent labeling, and super-resolution microscopy, and together these advances have vastly increased our quantitative understanding of the cell. This detailed knowledge has concomitantly opened the door for biophysical modeling on a cellular scale. There have been comprehensive models produced describing many processes such as motility, transport, gene regulation, and chemotaxis. However, in this review we focus on a specific set of phenomena, namely cell polarization, F-actin waves, and cytokinesis. In each case, we compare and contrast various published models, highlight the relevant aspects of the biology, and provide a sense of the direction in which the field is moving. PMID- 25124729 TI - Quality of measurements of acute surgical and traumatic wounds using a digital wound-analysing tool. AB - The aim of this study was to assess the reliability of measurements using a wound analysing tool and their interpretability. Wound surface areas and tissue types, such as granulation, slough and necrosis, in twenty digital photographs were measured using a specific software program. The ratio of these tissue types in a wound was calculated using a wound profile. We calculated the intraclass coefficient or kappa for reliability, standard error of measurement (SEM) and smallest detectable change (SDC). The inter-rater reliability intraclass correlation coefficient (ICC) was 0.99 for surface area, 0.76 for granulation, 0.67 for slough and 0.22 for necrosis. The profiles gave an overall kappa of 0.16. For test-retest reliability, the ICC was 0.99 for surface area, 0.81 for granulation, 0.80 for slough and 0.97 for necrosis. The agreement of the applied profiles in the test-retest was 66% (40-100). SEM and SDC for surface area were 0.10/0.27; for granulation, 6.88/19.08; for slough, 7.17/19.87; and for necrosis, 0.35/0.98, respectively. Measuring wound surface area and tissue types by means of digital photo analysis is a reliable and applicable method for monitoring wound healing in acute wounds in daily practice as well as in research. PMID- 25124730 TI - Hospitalizations and associated costs in a population-based study of children with Down syndrome born in Florida. AB - BACKGROUND: Our objective was to examine differences in hospital resource usage for children with Down syndrome by age and the presence of other birth defects, particularly severe and nonsevere congenital heart defects (CHDs). METHODS: This was a retrospective, population-based, statewide study of children with Down syndrome born 1998 to 2007, identified by the Florida Birth Defects Registry (FBDR) and linked to hospital discharge records for 1 to 10 years after birth. To evaluate hospital resource usage, descriptive statistics on number of hospitalized days and hospital costs were calculated. Results were stratified by isolated Down syndrome (no other coded major birth defect); presence of severe and nonsevere CHDs; and presence of major FBDR-eligible birth defects without CHDs. RESULTS: For 2552 children with Down syndrome, there were 6856 inpatient admissions, of which 68.9% occurred during the first year of life (infancy). Of the 2552 children, 31.7% (n = 808) had isolated Down syndrome, 24.0% (n = 612) had severe CHDs, 36.3% (n = 927) had nonsevere CHDs, and 8.0% (n = 205) had a major FBDR-eligible birth defect in the absence of CHD. Infants in all three nonisolated DS groups had significantly higher hospital costs compared with those with isolated Down syndrome. From infancy through age 4, children with severe CHDs had the highest inpatient costs compared with children in the other sub groups. CONCLUSION: Results support findings that for children with Down syndrome the presence of other anomalies influences hospital use and costs, and children with severe CHDs have greater hospital resource usage than children with other CHDs or major birth defects without CHDs. PMID- 25124732 TI - Identification of loci associated with late-onset psoriasis using dense genotyping of immune-related regions. AB - BACKGROUND: Chronic plaque psoriasis can be subdivided into two groups according to the age of onset: type 1 (early onset, before 40 years) and type 2 (late onset, at or beyond 40 years). So far, 36 genetic loci have been associated with early-onset psoriasis in genome-wide association studies of white populations, while few studies have investigated genetic susceptibility to late-onset psoriasis. OBJECTIVES: To characterize the genetics underpinning late-onset psoriasis. METHODS: We genotyped 543 cases of late-onset psoriasis and 4373 healthy controls using the Immunochip array, a dense genotyping chip containing single-nucleotide polymorphisms previously associated with autoimmune diseases. Imputation using SNP2HLA and stepwise logistic regression analysis was performed for markers spanning the human leucocyte antigen gene region. RESULTS: Two loci (HLA-C and IL12B) previously associated with early-onset psoriasis showed significant association at a genome-wide threshold in the current study (P < 5 * 10(-8)). Six more loci (TRAF3IP2, IL23R, RNF114, IFIH1, IL23A and HLA-A) showed study-wide significant association (P < 2.3 * 10(-5); calculated using Genetic type 1 error calculator). Additionally, we identified an association at IL1R1 on chromosome 2q13, which is not associated with early-onset disease. CONCLUSIONS: This is the largest study to date of genetic loci in late-onset psoriasis, and demonstrates the overlap that exists with early-onset psoriasis. It also suggests that some loci are associated exclusively with late-onset psoriasis. PMID- 25124731 TI - Phytolatex synthesized gold nanoparticles as novel agent to enhance sun protection factor of commercial sunscreens. AB - OBJECTIVE: To study the potential of phytolatex (latex of Jatropha gossypifolia) fabricated gold nanoparticles as promising candidate in sunscreen formulations for enhancement in sun protection factor. METHODS: In this study, plant latex was used as reducing and capping agent to synthesize gold nanoparticles. Latex fabricated gold nanoparticles were characterized by different analytical techniques such as UV-Vis spectroscopy, Fourier transforms infrared spectroscopy, dynamic light scattering, zeta potential, transmission electron microscopy and X ray diffraction. Potential of sunscreen preparations containing gold nanoparticles to protect skin from UV radiation was investigated by in vitro sun protection factor analysis. Transmission electron microscopy and UV-Vis spectroscopy techniques were used to get insight into mechanism by which AuNPs enhance sun protection factor of sunscreen. RESULTS: Monodisperse gold nanoparticles were synthesized using plant latex without need of hazardous chemical reducing and capping agents. Gold nanoparticles showed surface plasmon resonance peak at 550 nm in UV-Vis spectroscopic study. Gold nanoparticles were spherical and triangular in shape with size range of 30-50 nm. The zeta potential of gold nanoparticles was found to be -9.39 +/- 0.19 mV. XRD analysis confirmed face-centred cubic (fcc) structure of gold nanoparticles. Incorporation of latex synthesized gold nanoparticles (2 and 4 [% w/w]) into commercial sunscreens increased the sun protection factor from 2.43 +/- 0.74 to 24.11 +/- 0.46% than sunscreen devoid of gold nanoparticles. From UV-Vis absorption spectroscopy and TEM analysis, it was observed that gold nanoparticles enhance the sun protection factor of commercial sunscreens due to reflection and scattering of UV radiation. CONCLUSION: Phytolatex synthesized gold nanoparticle is novel agent to enhance sun protection factor of commercial sunscreens. Gold nanoparticles aggregation in commercial sunscreen was the main factor behind SPF enhancement. This study showed that gold nanoparticles are potent alternative to traditionally used hazardous titanium dioxide and zinc oxide nanoparticles in sunscreen. PMID- 25124733 TI - Influence of repeated infusion of capsaicin-contained red pepper sauce on esophageal secondary peristalsis in humans. AB - BACKGROUND: The transient receptor potential vanilloid 1 has been implicated as a target mediator for heartburn perception and modulation of esophageal secondary peristalsis. Our aim was to determine the effect of repeated esophageal infusion of capsaicin-contained red pepper sauce on heartburn perception and secondary peristalsis in healthy adults. METHODS: Secondary peristalsis was performed with mid-esophageal injections of air in 15 healthy adults. Two separate protocols including esophageal infusion with saline and capsaicin-contained red pepper sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were randomly performed. KEY RESULTS: After repeated infusion of capsaicin-contained red pepper sauce, the threshold volume to activate secondary peristalsis was significantly increased during slow (p < 0.001) and rapid air injections (p = 0.004). Acute infusion of capsaicin-contained red pepper sauce enhanced heartburn perception (p < 0.001), but the intensity of heartburn perception was significantly reduced after repeated capsaicin-contained red pepper sauce infusion (p = 0.007). Acute infusion of capsaicin-contained red pepper sauce significantly increased pressure wave amplitudes of distal esophagus during slow (p = 0.003) and rapid air injections (p = 0.01), but repeated infusion of capsaicin-contained red pepper sauce significantly decreased pressure wave amplitude of distal esophagus during slow (p = 0.0005) and rapid air injections (p = 0.003). CONCLUSIONS & INFERENCES: Repeated esophageal infusion of capsaicin appears to attenuate heartburn perception and inhibit distension-induced secondary peristalsis in healthy adults. These results suggest capsaicin sensitive afferents in modulating sensorimotor function of secondary peristalsis in human esophagus. PMID- 25124735 TI - TiO2 hollow spheres composed of highly crystalline nanocrystals exhibit superior lithium storage properties. AB - While the synthesis of TiO2 hollow structures is well-established, in most cases it is particularly difficult to control the crystallization of TiO2 in solution or by calcination. As a result, TiO2 hollow structures do not really exhibit enhanced lithium storage properties. Herein, we report a simple and cost effective template-assisted method to synthesize anatase TiO2 hollow spheres composed of highly crystalline nanocrystals, in which carbonaceous (C) spheres are chosen as the removable template. The release of gaseous species from the combustion of C spheres may inhibit the growth of TiO2 crystallites so that instead small TiO2 nanocrystals are generated. The small size and high crystallinity of primary TiO2 nanoparticles and the high structural integrity of the hollow spheres gives rise to significant improvements in the cycling stability and rate performance of the TiO2 hollow spheres. PMID- 25124734 TI - First case of multidrug-resistant blaNDM-1- and blaOXA-232-carrying Klebsiella pneumoniae and its probable cross-transmission in a French hospital. PMID- 25124737 TI - More-frequent extreme northward shifts of eastern Indian Ocean tropical convergence under greenhouse warming. AB - The Intertropical Convergence Zone (ITCZ) in the tropical eastern Indian Ocean exhibits strong interannual variability, often co-occurring with positive Indian Ocean Dipole (pIOD) events. During what we identify as an extreme ITCZ event, a drastic northward shift of atmospheric convection coincides with an anomalously strong north-minus-south sea surface temperature (SST) gradient over the eastern equatorial Indian Ocean. Such shifts lead to severe droughts over the maritime continent and surrounding islands but also devastating floods in southern parts of the Indian subcontinent. Understanding future changes of the ITCZ is therefore of major scientific and socioeconomic interest. Here we find a more-than-doubling in the frequency of extreme ITCZ events under greenhouse warming, estimated from climate models participating in the Coupled Model Intercomparison Project phase 5 that are able to simulate such events. The increase is due to a mean state change with an enhanced north-minus-south SST gradient and a weakened Walker Circulation, facilitating smaller perturbations to shift the ITCZ northwards. PMID- 25124736 TI - Epigallocatechin-3-gallate functions as a physiological regulator by modulating the jasmonic acid pathway. AB - Flavonoids, a class of plant polyphenols derived from plant secondary metabolism, play important roles in plant development and have beneficial effects on human health. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol, and its molecular and biochemical mechanism have been followed with interest. The shared signaling heritage or convergence of organisms has allowed us to extend this research into the model plant, Arabidopsis thaliana. Here, we showed that EGCG could promote jasmonic acid (JA) signaling in A. thaliana. EGCG not only inhibited seed germination but also elevated the resistance to necrotrophic Botrytis cinerea, partly by altering the relative strength of JA signaling. Accordingly, JA marker gene induction, seed germination inhibition and the increased resistance to B. cinerea were attenuated in the JA-insensitive coi1-2 mutant. The coi1-2 mutant was partially insensitive to the treatment of EGCG, further implicating the function of EGCG in JA signaling and/or perception. Our results indicate that EGCG, a member of the flavonoid class of polyphenols, affects signal processing in seed development and disease susceptibility via modulation of JA signaling. PMID- 25124738 TI - Neurotoxicology and development: human, environmental and social impacts. AB - The 12th International symposium of the Scientific Committee on Neurotoxicology and Psychophysiology, International Commission on Occupational Health was held in Cape Town, South Africa on March 24-27, 2013. Reflecting the meeting aiming to build greater focus on challenges facing working populations and communities in developing countries, the Symposium theme was Neurotoxicology and Development: Human, Environmental and Social Impacts. A total of 23 countries were represented with strong participation from 5 African countries. In addition to the more traditional topics of these Symposia, like metal, solvents and pesticides neurotoxicity, the conference embraced several new themes including affective disorders arising from chemical exposure, neurodevelopmental impacts in early life and novel approaches to genetic and epigenetic biomarkers for the assessment of neurotoxic impact. The theme of the conference prompted extensive discussions, which have laid the basis for a number of new directions for research, advocacy and capacity building to prevent and manage chemical neurotoxicity in workplace and community settings across the globe. PMID- 25124739 TI - Prenatal and postnatal lead exposure and cognitive development of infants followed over the first three years of life: a prospective birth study in the Pearl River Delta region, China. AB - PURPOSE: Our pilot studies showed that there was a significant relationship between low cord blood levels and scores of neonatal behavioral neurological assessment. The study was further to probe the adverse cognitive effects induced by low-level lead exposure during prenatal and postnatal period. METHOD: Totally 362 mothers with their infants located the PRD, Guangdong, China participated in the study during their stay in these center: 141 in the high lead group [umbilical-cord blood lead levels (UCBLLs)>=3.92MUg/dl] and 102 in the low lead group (UCBLLs<=1.89MUg/dl). The other 137 subjects failed to complete the study for a variety of reasons. Blood Lead levels (BLLs) were measured by atomic absorption spectrophotometry, equipped with a graphite furnace. The developmental functioning of infants and children was assessed with BSID-II. The children's birth outcome and the rest of information were obtained from their medical records or a comprehensive questionnaire from their parents, which contained demographic characteristics, lifestyle, mother's IQ and environmental lead sources, etc. RESULTS: Of 380, 243 newborns (63.95%) had complete data collection for all variables included at 6, 12, 24 and 36 months of age. The mean UCBLLs for high and low lead group were 5.63+/-0.32MUg/dl and 1.35+/-0.26MUg/dl, respectively. Significant inverse associations have been found between the UCBLLs and the MDI and the PDI. The associations might attenuate over subsequent years. BLLs at 24 months were significantly associated, in an inverse direction, with MDI at 24 and 36 months. The observed trend of cognitive deficit beginning at 6 months of life might persist, and even develop over the coming years. A positive significant effect of home nurture environment was observed on MDI scores at 12, 24, 36 months of age and PDI scores at 24 and 36 months of age. CONCLUSION: Our study demonstrates that prenatal and postnatal lead exposure as low as 5MUg/dl has an adverse effect on neurodevelopment, best arrested by measuring UCBLLs and BLLs at 24 months of age, and suggest a reference for a blood lead critical value below 5MUg/dL. The collective evidence indicate that low lead exposure must be addressed appropriately by health policy makers and argues for an improvement of home nurture environment, i.e., reduce the burden of Pb on children and, strengthen the training of cognitive ability. PMID- 25124740 TI - Dramatic decrease in fluoroquinolones in the pediatric population in Korea. AB - PURPOSE: This study was performed to evaluate the change of prescribing patterns after the regulatory action regarding fluoroquinolones in pediatric patients. METHODS: We conducted a time series analysis using the Korea Health Insurance Review and Assessment Service National Patients Sample database. Study subjects consisted of pediatric patients under 18 years of age who were prescribed antibiotics at least once (ATC code, J01) before (January 2009-December 2009) and after implementation (January 2010-December 2011) of the regulation. The use of fluoroquinolones was defined as the use of the following antibiotics for at least once in pediatric patients: ofloxacin, ciprofloxacin, norfloxacin, lomefloxacin, levofloxacin, and gemifloxacin. We calculated the number of pediatric fluoroquinolone users for each month. The difference between proportions before and after the regulation was estimated as relative and absolute reduction of fluoroquinolone use. We calculated 95% confidence intervals (CI). RESULTS: We identified 4, 945, 169 antibiotic prescriptions in 484, 914 pediatric patients. During the 12-month period before implementation, percentage of fluoroquinolone use was 4.81% (95% CI: 4.70-4.91%, N = 8001). We observed a rapid decrease in the monthly number of fluoroquinolone users in pediatric population after the implementation of regulatory action. In the year after regulatory action, the percentage of fluoroquinolone use was only 0.26% (95% CI: 0.24-0.28%, N = 834). Overall, there was a 94.55% relative reduction (95% CI: 88.02-101.56%) in the use of fluoroquinolones. CONCLUSION: Korean regulatory actions regarding fluoroquinolones had an effect of reducing use in pediatric population. PMID- 25124741 TI - Simultaneous high-resolution detection of multiple transcripts combined with localization of proteins in whole-mount embryos. AB - BACKGROUND: Whole-mount in situ hybridization (WISH) is a fundamental tool for studying the spatio-temporal expression pattern of RNA molecules in intact embryos and tissues. The available methodologies for detecting mRNAs in embryos rely on enzymatic activities and chemical reactions that generate diffusible products, which are not fixed to the detected RNA, thereby reducing the spatial resolution of the technique. In addition, current WISH techniques are time consuming and are usually not combined with methods reporting the expression of protein molecules. RESULTS: The protocol we have developed and present here is based on the RNAscope technology that is currently employed on formalin-fixed, paraffin-embedded and frozen tissue sections for research and clinical applications. By using zebrafish embryos as an example, we provide a robust and rapid method that allows the simultaneous visualization of multiple transcripts, demonstrated here for three different RNA molecules. The optimized procedure allows the preservation of embryo integrity, while exhibiting excellent signal-to noise ratios. Employing this method thus allows the determination of the spatial expression pattern and subcellular localization of multiple RNA molecules relative to each other at high resolution, in the three-dimensional context of the developing embryo or tissue under investigation. Lastly, we show that this method preserves the function of fluorescent proteins that are expressed in specific cells or cellular organelles and conserves antigenicity, allowing protein detection using antibodies. CONCLUSIONS: By fine-tuning the RNAscope technology, we have successfully redesigned the protocol to be compatible with whole-mount embryo samples. Using this robust method for zebrafish and extending it to other organisms would have a strong impact on research in developmental, molecular and cell biology. Of similar significance would be the adaptation of the method to whole-mount clinical samples. Such a protocol would contribute to biomedical research and clinical diagnostics by providing information regarding the three-dimensional expression pattern of clinical markers. PMID- 25124742 TI - Retronasal odor of dried bonito stock induces umami taste and improves the palatability of saltiness. AB - A traditional Japanese umami-rich stock, dried bonito stock, was reported to improve the palatability of a low-salt diet due to its characteristic aroma. Two pathways are available for the presentation of odors: the orthonasal and retronasal pathways. Aroma is perceived through the orthonasal pathway. In contrast, retronasal application of odors is thought to evoke different sensations from the orthonasal pathway, which is typically perceived as taste and modifies taste. Therefore, the effect of retronasal odor on salt-reduction might be different from that of aroma, that is, orthonasal odor. Thus, the effects of the retronasal odor of dried bonito stock on the enhancement and improvement of palatability upon salt reduction were examined using sensory evaluation. Moreover, the contributions to flavor expression and palatability of dried bonito stock were also investigated. Although the retronasal odor of dried bonito did not enhance saltiness, it improved the palatability of saltiness. In the presence of no tastants except 0.68% NaCl, a content 15% less than that of Japanese traditional soup, the retronasal odor of dried bonito generated umami, enhanced the suitability for dried bonito stock, and increased palatability. This indicates that the retronasal odor of dried bonito stock could improve the palatability of a salt-reduced diet. These findings can be applied to the development of new seasonings for improving the palatability of salt-reduced foods. PMID- 25124744 TI - Isoflurane reduces the ischemia reperfusion injury surge: a longitudinal study with MRI. AB - BACKGROUND: Recent studies show neuroprotective benefits of isoflurane (ISO) administered during cerebral ischemia. However, the available studies evaluated cerebral injury only at a single time point following the intervention and thus the longitudinal effect of ISO on ischemic tissues remains to be investigated. OBJECTIVE: The objective of the present study was to investigate the longitudinal effect of ISO treatment in counteracting the deleterious effect of ischemia by evoking the transcription factor, hypoxia inducible factor-1 (HIF-1), and vascular endothelial growth factor (VEGF). METHODS: Focal cerebral ischemia was induced in 70 rats by filament medial cerebral artery occlusion (MCAo) method. MCAo rats were randomly assigned to control (90 min ischemia) and MCAo+ISO (90 min ischemia+2% ISO) groups. Infarct volume, edema, intracerebral hemorrhage (ICH), and regional cerebral blood flow (rCBF) were measured in eight in vivo sequential MR imaging sessions for 3 weeks. Western blot analysis and immunofluorescence were used to determine the expression level of HIF-1alpha (the regulatable subunit of HIF-1) and VEGF proteins. RESULTS: ISO inhalation during ischemia significantly decreased the surge of infarct volume, edema, ICH, and reduced the mortality rate (p<0.01). ISO transiently altered the rCBF, significantly enhanced the expression of HIF-1alpha and VEGF, and decreased the immune cell infiltration. Locomotor dysfunction was ameliorated at a significantly faster pace, and the benefit was seen to persist up to three weeks. CONCLUSION: Treatment with ISO during ischemia limits the deadly surge in the dynamics of ischemia reperfusion injury with no observed long-term inverse effect. PMID- 25124743 TI - Enhanced neurocognitive functioning and positive temperament in twins discordant for bipolar disorder. AB - OBJECTIVE: Based on evidence linking creativity and bipolar disorder, a model has been proposed whereby factors influencing liability to bipolar disorder confer certain traits with positive effects on reproductive fitness. The authors tested this model by examining key traits known to be associated with evolutionary fitness, namely, temperament and neurocognition, in individuals carrying liability for bipolar disorder. Schizophrenia probands and their co-twins were included as psychiatric controls. METHOD: Twin pairs discordant for bipolar disorder and schizophrenia and control pairs were identified through the Swedish Twin Registry. The authors administered a neuropsychological test battery and temperament questionnaires to samples of bipolar probands, bipolar co-twins, schizophrenia probands, schizophrenia co-twins, and controls. Multivariate mixed model analyses of variance were conducted to compare groups on temperament and neurocognitive scores. RESULTS: Bipolar co-twins showed elevated scores on a "positivity" temperament scale compared with controls and bipolar probands, while bipolar probands scored higher on a "negativity" scale compared with their co twins and controls, who did not differ. Additionally, bipolar co-twins showed superior performance compared with controls on tests of verbal learning and fluency, while bipolar probands showed performance decrements across all neurocognitive domains. In contrast, schizophrenia co-twins showed attenuated impairments in positivity and overall neurocognitive functioning relative to their ill proband counterparts. CONCLUSIONS: These findings suggest that supra normal levels of sociability and verbal functioning may be associated with liability for bipolar disorder. These effects were specific to liability for bipolar disorder and did not apply to schizophrenia. Such benefits may provide a partial explanation for the persistence of bipolar illness in the population. PMID- 25124746 TI - Use of cholesterol-loaded cyclodextrin in donkey semen cryopreservation improves sperm viability but results in low fertility in mares. AB - The use of cholesterol-loaded cyclodextrin (CLC) on semen cryopreservation has been related with better sperm viability in several species; however, the effect on fertility is not known in donkey semen. Ejaculates (n = 25) from five donkeys were diluted in S-MEDIUM with 0, 1, 2 or 3 mg of CLC/120 * 10(6) spermatozoa. Semen was frozen, and thawed samples were evaluated by computer-assisted sperm analyser system (CASA), supravital test, hyposmotic swelling test and fluorescent dyes to assess the integrity of sperm membranes. Mares (n = 60) were inseminated with frozen-thawed semen treated with the doses of 0 or 1 mg CLC. Percentages of sperm with progressive motility and with functional plasma membrane were greater (p < 0.05) in the CLC-treated groups than in the control. Percentages of intact plasma membrane and intact plasma membrane and acrosome detected by fluorescent dyes were also greater (p < 0.05) in CLC-treated groups. Although no difference (p > 0.05) in conception rates was detected between groups (control, 3/30, 10%; CLC-treated, 1/30, 3.3%), fertility was low for artificial insemination programs in mares. Therefore, we firstly demonstrated that frozen semen treated with CLC in S-MEDIA extender before freezing improves the in vitro sperm viability, but semen treated or not with CLC in S-MEDIUM extender results in a very low conception rate in mares inseminated with thawed donkey semen. PMID- 25124747 TI - Evaluating disease-modifying agents: a simulation framework for Alzheimer's disease. AB - BACKGROUND: Considerable advances have been made in modeling Alzheimer's disease (AD), with a move towards individual-level rather than cohort models and simulations that consider multiple dimensions when evaluating disease severity. However, the possibility that disease-modifying agents (DMAs) may emerge requires an update of existing modeling frameworks. OBJECTIVES: The aim of this study was to develop a simulation allowing for economic evaluation of DMAs in AD. METHODS: The model was developed based on a previously published, well-validated, discrete event simulation which measures disease severity on the basis of cognition, behaviour, and function, and captures the interrelated changes in these measures for individuals. The updated model adds one more domain, patient dependence, in addition to cognition, behaviour, and function to better characterize disease severity. Furthermore, the model was modified to have greater flexibility in assessing the impact of various important assumptions, such as the long-term effectiveness of DMAs and their impact on survival, on model outcomes. A validation analysis was performed to examine how well the model predicted change in disease severity among patients not receiving DMA treatment by comparing model results to those observed in two recent phase III clinical trials of bapineuzumab. In addition, various hypothetical scenarios were tested to demonstrate the improved features of the model. RESULTS: Validation results show that the model closely predicts the mean changes in disease severity over 18 months. Results from different hypothetical scenarios show that the model allows for credible assessment of those major uncertainties surrounding the long-term effectiveness of DMAs, including the potential impact of improved survival with DMA treatment. They also indicate that varying these assumptions could have a major impact on the value of DMAs. CONCLUSIONS: The updated economic model has good predictive power, but validation against longer-term outcomes is still needed. Our analyses also demonstrate the importance of designing a model with sufficient flexibility such that the model allows for assessment of the impact of key sources of uncertainty on the value of DMAs. PMID- 25124748 TI - Typology of individuals with substance dependence based on a Montreal longitudinal catchment area study. AB - This study sought to develop a typology of individuals with substance dependence (ISD) based on a longitudinal survey (n = 2,434) and 121 ISD. The latter were divided into three groups: newly abstinent individuals, chronic dependents and acute dependents. Individuals' typology was developed by cluster analysis. Newly abstinent individuals had fewer emotional problems and mental disorders in the previous 12 months. Four classes of ISD were identified, labelled respectively "chronic multi-substance consumption and mental disorders comorbidities," "multi substance consumption," "alcohol and marijuana consumption" and "alcohol consumption only." Strategies adapted to each of these profiles could be promoted for more effective treatment. PMID- 25124750 TI - Implementing a medical screening and referral program for rural emergency departments. AB - CONTEXT: Emergency Department (ED) overcrowding due to nonemergent use is an ongoing concern. In 2011, a regional health system that primarily serves rural communities in Texas instituted a new program to medically screen and refer nonemergent patients to nearby affiliated rural health clinics (RHCs). PURPOSE: This formative evaluation describes the program goals, process, and early implementation experiences at 2 sites that adopted the program before wider implementation within the rural health system. METHODS: Primary data collection including document review, internal stakeholder interviews, and direct observation of program processes were used for this formative evaluation of program implementation in light of program goals and objectives. Fourteen key informants were asked questions related to the program concept, structure, and implementation. RESULTS: The program, as implemented, aligned with initial program goals, but it was dependent on ED screening staff and RHC availability. Some adjustments to the program were needed, including RHC hours, consistency among staff in making referrals, patient education, and improving patient uptake on the referral. Stakeholders reported lessons learned related to training, staff buy-in, Emergency Medical Treatment and Labor Act (EMTALA), and intraorganizational cooperation. DISCUSSION: The system was able to leverage excess capacity of affiliated RHCs to accommodate low-acuity patients referred from the ED and may lead to improvements in Triple Aim goals of increased patient satisfaction, better population health and outcomes, and lower per capita costs. Lessons learned from this program may inform similar processes aimed to reduce nonemergency ED utilization by other rural health systems. PMID- 25124749 TI - Complement factor C5a induces atherosclerotic plaque disruptions. AB - Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE(-/-) mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. PMID- 25124752 TI - Impulsive exponential synchronization of randomly coupled neural networks with Markovian jumping and mixed model-dependent time delays. AB - In this paper, the exponential synchronization problem for an array of N randomly coupled neural networks with Markovian jump and mixed model-dependent time delays via impulsive control is investigated. The jump parameters are determined by a continuous-time, discrete-state Markovian chain, and the mixed time delays under consideration comprise both discrete and continuous distributed delays. By making use of the Kronecker product and some useful techniques, a novel Lyapunov Krasovskii functional suitable for handling distributed delays was proposed and then we show that the addressed synchronization problem is solvable if a set of linear matrix inequalities (LMIs) are feasible. The results presented in this paper generalize and improve many known results. Two numerical examples are also given to show the effectiveness of the theoretical results. PMID- 25124753 TI - Global exponential almost periodicity of a delayed memristor-based neural networks. AB - In this paper, the existence, uniqueness and stability of almost periodic solution for a class of delayed memristor-based neural networks are studied. By using a new Lyapunov function method, the neural network that has a unique almost periodic solution, which is globally exponentially stable is proved. Moreover, the obtained conclusion on the almost periodic solution is applied to prove the existence and stability of periodic solution (or equilibrium point) for delayed memristor-based neural networks with periodic coefficients (or constant coefficients). The obtained results are helpful to design the global exponential stability of almost periodic oscillatory memristor-based neural networks. Three numerical examples and simulations are also given to show the feasibility of our results. PMID- 25124751 TI - Isotopic ratio based source apportionment of children's blood lead around coking plant area. AB - Lead exposure in the environment is a major hazard affecting human health, particularly for children. The blood lead levels in the local children living around the largest coking area in China were measured, and the source of blood lead and the main pathways of lead exposure were investigated based on lead isotopic ratios ((207)Pb/(206)Pb and (208)Pb/(206)Pb) in blood and in a variety of media, including food, airborne particulate matter, soil, dust and drinking water. The children's blood lead level was 5.25 (1.59 to 34.36 as range) MUg dL( 1), lower than the threshold in the current criteria of China defined by the US Centers for Disease Control (10 MUg dL(-1)). The isotopic ratios in the blood were 2.111+/-0.018 for (208)Pb/(206)Pb and 0.864+/-0.005 for (207)Pb/(206)Pb, similar to those of vegetables, wheat, drinking water, airborne particulate matter, but different from those of vehicle emission and soil/dust, suggesting that the formers were the main pathway of lead exposure among the children. The exposure pathway analysis based on the isotopic ratios and the human health risk assessment showed that dietary intake of food and drinking water contributed 93.67% of total exposed lead. The study further indicated that the coal used in the coking plant is the dominant pollution source of lead in children's blood. PMID- 25124745 TI - Vector platforms for gene therapy of inherited retinopathies. AB - Inherited retinopathies (IR) are common untreatable blinding conditions. Most of them are inherited as monogenic disorders, due to mutations in genes expressed in retinal photoreceptors (PR) and in retinal pigment epithelium (RPE). The retina's compatibility with gene transfer has made transduction of different retinal cell layers in small and large animal models via viral and non-viral vectors possible. The ongoing identification of novel viruses as well as modifications of existing ones based either on rational design or directed evolution have generated vector variants with improved transduction properties. Dozens of promising proofs of concept have been obtained in IR animal models with both viral and non-viral vectors, and some of them have been relayed to clinical trials. To date, recombinant vectors based on the adeno-associated virus (AAV) represent the most promising tool for retinal gene therapy, given their ability to efficiently deliver therapeutic genes to both PR and RPE and their excellent safety and efficacy profiles in humans. However, AAVs' limited cargo capacity has prevented application of the viral vector to treatments requiring transfer of genes with a coding sequence larger than 5 kb. Vectors with larger capacity, i.e. nanoparticles, adenoviral and lentiviral vectors are being exploited for gene transfer to the retina in animal models and, more recently, in humans. This review focuses on the available platforms for retinal gene therapy to fight inherited blindness, highlights their main strengths and examines the efforts to overcome some of their limitations. PMID- 25124756 TI - Early embryonic specification of vertebrate cranial placodes. AB - Cranial placodes contribute to many sensory organs and ganglia of the vertebrate head. The olfactory, otic, and lateral line placodes form the sensory receptor cells and neurons of the nose, ear, and lateral line system; the lens placode develops into the lens of the eye; epibranchial, profundal, and trigeminal placodes contribute sensory neurons to cranial nerve ganglia; and the adenohypophyseal placode gives rise to the anterior pituitary, a major endocrine control organ. Despite these differences in fate, all placodes are now known to originate from a common precursor, the preplacodal ectoderm (PPE). The latter is a horseshoe-shaped domain of ectoderm surrounding the anterior neural plate and neural crest and is defined by expression of transcription factor Six1, its cofactor Eya1, and other members of the Six and Eya families. Studies in zebrafish, Xenopus, and chick reveal that the PPE is specified together with other ectodermal territories (epidermis, neural crest, and neural plate) during early embryogenesis. During gastrulation, domains of ventrally (e.g., Dlx3/Dlx5, GATA2/GATA3, AP2, Msx1, FoxI1, and Vent1/Vent2) and dorsally (e.g., Zic1, Sox3, and Geminin) restricted transcription factors are established in response to a gradient of BMP and help to define non-neural and neural competence territories, respectively. At neural plate stages, the PPE is then induced in the non-neural competence territory by signals from the adjacent neural plate and mesoderm including FGF, BMP inhibitors, and Wnt inhibitors. Subsequently, signals from more localized signaling centers induce restricted expression domains of various transcription factors within the PPE, which specify multiplacodal areas and ultimately individual placodes. For further resources related to this article, please visit the WIREs website. CONFLICT OF INTEREST: The author has declared no conflicts of interest for this article. PMID- 25124757 TI - Cell-intrinsic timing in animal development. AB - In certain instances we can witness cells controlling the sequence of their behaviors as they divide and differentiate. Striking examples occur in the nervous systems of animals where the order of differentiated cell types can be traced to internal changes in their progenitors. Elucidating the molecular mechanisms underlying such cell fate succession has been of interest for its role in generating cell type diversity and proper tissue structure. Another well studied instance of developmental timing occurs in the larva of the nematode Caenorhabditis elegans, where the heterochronic gene pathway controls the succession of a variety of developmental events. In each case, the identification of molecules involved and the elucidation of their regulatory relationships is ongoing, but some important factors and dynamics have been revealed. In particular, certain homologs of worm heterochronic factors have been shown to work in neural development, alerting us to possible connections among these systems and the possibility of universal components of timing mechanisms. These connections also cause us to consider whether cell-intrinsic timing is more widespread, regardless of whether multiple differentiated cell types are produced in any particular order. For further resources related to this article, please visit the WIREs website. CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. PMID- 25124759 TI - Arterial tortuosity in patients with Filamin A- associated vascular aneurysms. PMID- 25124755 TI - Developmental programs of lung epithelial progenitors: a balanced progenitor model. AB - The daunting task of lung epithelium development is to transform a cluster of foregut progenitors into a three-dimensional (3D) tubular network with distinct cell types distributed at their appropriate locations. A complete understanding of lung development needs to address not only how, but also where, different cell types form. We propose that the lung epithelium forms through regulated deployment of three developmental programs: branching morphogenesis to expand progenitors and build a tree-like tubular network, airway differentiation to specify cells for the proximal conducting airways, and alveolar differentiation to specify cells for the peripheral gas exchange region. Each developmental program has its unique morphological features and molecular control mechanisms; their spatiotemporal coordination can be accounted for in a balanced progenitor model where progenitors balance between alternative developmental programs in response to spatiotemporal cues. This model integrates progenitor morphogenesis and differentiation, and provides new insights to lung immaturity in preterm birth and lung evolution. Advanced gene targeting and 3D imaging tools are needed to achieve a comprehensive understanding of lung epithelial progenitors on molecular, cellular, and morphological levels. For further resources related to this article, please visit the WIREs website. CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. PMID- 25124761 TI - The movement of the non-cell-autonomous transcription factor, SHORT-ROOT relies on the endomembrane system. AB - Plant cells are able to convey positional and developmental information between cells through the direct transfer of transcription factors. One well studied example of this is the SHORT-ROOT (SHR) protein, which moves from the stele into the neighboring ground tissue layer to specify endodermis. While it has been shown that SHR trafficking relies on plasmodesmata (PD), and interaction with the SHR INTERACTING EMBRYONIC LETHAL (SIEL) protein, little information is known about how SHR trafficking is controlled or how SIEL promotes the movement of SHR. Here we show that SHR can move from multiple different cell types in the root. Analysis of subcellular localization indicates that in the cytoplasm of root or leaf cells, SHR localizes to endosomes in a SIEL-dependent manner. Interference of early and late endosomes disrupts intercellular movement of SHR. Our findings reveal an essential role for the plant endomembrane, independent of secretion, in the intercellular trafficking of SHR. PMID- 25124754 TI - Maternal control of the Drosophila dorsal-ventral body axis. AB - The pathway that generates the dorsal-ventral (DV) axis of the Drosophila embryo has been the subject of intense investigation over the previous three decades. The initial asymmetric signal originates during oogenesis by the movement of the oocyte nucleus to an anterior corner of the oocyte, which establishes DV polarity within the follicle through signaling between Gurken, the Drosophila Transforming Growth Factor (TGF)-alpha homologue secreted from the oocyte, and the Drosophila Epidermal Growth Factor Receptor (EGFR) that is expressed by the follicular epithelium cells that envelop the oocyte. Follicle cells that are not exposed to Gurken follow a ventral fate and express Pipe, a sulfotransferase that enzymatically modifies components of the inner vitelline membrane layer of the eggshell, thereby transferring DV spatial information from the follicle to the egg. These ventrally sulfated eggshell proteins comprise a localized cue that directs the ventrally restricted formation of the active Spatzle ligand within the perivitelline space between the eggshell and the embryonic membrane. Spatzle activates Toll, a transmembrane receptor in the embryonic membrane. Transmission of the Toll signal into the embryo leads to the formation of a ventral-to-dorsal gradient of the transcription factor Dorsal within the nuclei of the syncytial blastoderm stage embryo. Dorsal controls the spatially specific expression of a large constellation of zygotic target genes, the Dorsal gene regulatory network, along the embryonic DV circumference. This article reviews classic studies and integrates them with the details of more recent work that has advanced our understanding of the complex pathway that establishes Drosophila embryo DV polarity. For further resources related to this article, please visit the WIREs website. CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. PMID- 25124760 TI - Structural insights for HIV-1 therapeutic strategies targeting Vif. AB - HIV-1 viral infectivity factor (Vif) is a viral accessory protein that is required for HIV-1 infection due largely to its role in recruiting antiretroviral factors of the APOBEC3 (apolipoprotein B editing catalytic subunit-like 3) family to an E3 ubiquitin ligase complex for polyubiquitylation and proteasomal degradation. The crystal structure of the (near) full-length Vif protein in complex with Elongin (Elo)B/C, core-binding factor (CBF)beta and Cullin (Cul)5 revealed that Vif has a novel structural fold. In our opinion the structural data revealed not only the protein-protein interaction sites that determine Vif stability and interaction with cellular proteins, but also motifs driving Vif homodimerization, which are essential in Vif functionality and HIV-1 infection. Vif-mediated protein-protein interactions are excellent targets for a new class of antiretroviral therapeutics to combat AIDS. PMID- 25124762 TI - A mathematical model of the human metabolic system and metabolic flexibility. AB - In healthy subjects some tissues in the human body display metabolic flexibility, by this we mean the ability for the tissue to switch its fuel source between predominantly carbohydrates in the postprandial state and predominantly fats in the fasted state. Many of the pathways involved with human metabolism are controlled by insulin and insulin-resistant states such as obesity and type-2 diabetes are characterised by a loss or impairment of metabolic flexibility. In this paper we derive a system of 12 first-order coupled differential equations that describe the transport between and storage in different tissues of the human body. We find steady state solutions to these equations and use these results to nondimensionalise the model. We then solve the model numerically to simulate a healthy balanced meal and a high fat meal and we discuss and compare these results. Our numerical results show good agreement with experimental data where we have data available to us and the results show behaviour that agrees with intuition where we currently have no data with which to compare. PMID- 25124763 TI - Modelling the impact of marine reserves on a population with depensatory dynamics. AB - In this study, we use a spatially implicit, stage-structured model to evaluate marine reserve effectiveness for a fish population exhibiting depensatory (strong Allee) effects in its dynamics. We examine the stability and sensitivity of the equilibria of the modelled system with regards to key system parameters and find that for a reasonable set of parameters, populations can be protected from a collapse if a small percentage of the total area is set aside in reserves. Furthermore, the overall abundance of the population is predicted to achieve a maximum at a certain ratio A of reserve area to fished area, which depends heavily on the other system parameters such as the net export rate of fish from the marine reserves to the fished areas. This finding runs contrary to the contested "equivalence at best" result when comparing fishery management through traditional catch or effort control and management through marine reserves. Lastly, we analyse the problem from a bioeconomics perspective by computing the optimal harvesting policy using Pontryagin's Maximum Principle, which suggests that the value for A which maximizes the optimal equilibrium fishery yield also maximizes population abundance when the cost per unit harvest is constant, but can increase substantially when the cost per unit harvest increases with the area being harvested. PMID- 25124764 TI - Age trajectories of mortality from all diseases in the six most populated countries of the South America during the last decades. AB - Age trajectories of total mortality represent an irreplaceable source of information about aging. In principle, age affects mortality from all diseases differently than it affects mortality from external causes. External causes (accidents) are excluded here from all causes, and the resultant category "all diseases" is tested as a helpful tool to better understand the relationship between mortality and age. Age trajectories of all-diseases mortality are studied in the six most populated countries of the South America during 1996-2010. The numbers of deaths for specific causes of death are extracted from the database of WHO, where the ICD-10 revision is used. The all-diseases mortality shows a strong minimum, which is hidden in total mortality. Two simple deterministic models fit the age trajectories of all-diseases mortality. The inverse proportion between mortality and age fits the mortality decreases up to minimum value in all six countries. All previous models describing mortality decline after birth are discussed. Theoretical relationships are derived between the parameter in the first model and standard mortality indicators: Infant mortality, Neonatal mortality, and Postneonatal mortality. The Gompertz model extended with a small positive quadratic element fit the age trajectories of all-diseases mortality after the age of 10 years. PMID- 25124765 TI - Dynamics of a producer-grazer model incorporating the effects of excess food nutrient content on grazer's growth. AB - Modeling under the framework of ecological stoichiometric allows the investigation of the effects of food quality on food web population dynamics. Recent discoveries in ecological stoichiometry suggest that grazer dynamics are affected by insufficient food nutrient content (low phosphorus (P)/carbon (C) ratio) as well as excess food nutrient content (high P:C). This phenomenon is known as the "stoichiometric knife edge." While previous models have captured this phenomenon, they do not explicitly track P in the producer or in the media that supports the producer, which brings questions to the validity of their predictions. Here, we extend a Lotka-Volterra-type stoichiometric model by mechanistically deriving and tracking P in the producer and free P in the environment in order to investigate the growth response of Daphnia to algae of varying P:C ratios. Bifurcation analysis and numerical simulations of the full model, that explicitly tracks phosphorus, lead to quantitative different predictions than previous models that neglect to track free nutrients. The full model shows that the fate of the grazer population can be very sensitive to excess nutrient concentrations. Dynamical free nutrient pool seems to induce extreme grazer population density changes when total nutrient is in an intermediate range. PMID- 25124766 TI - Ecohydrology of agroecosystems: quantitative approaches towards sustainable irrigation. AB - Irrigation represents one of the main strategies to enhance and stabilize agricultural productivity, by mitigating the effects of rainfall vagaries. In the face of the projected growth in population and in biofuel demands, as well as shifts in climate and dietary habits, a more sustainable management of water resources in agroecosystems is needed. The field of ecohydrology, traditionally focusing on natural ecosystems, has the potential to offer the necessary quantitative tools to assess and compare agricultural enterprises across climates, soil types, crops, and irrigation strategies, accounting for the unpredictability of the hydro-climatic forcing. Here, agricultural sustainability and productivity are assessed with reference to water productivity (defined as the ratio between yield and total supplied water), yields, water requirements, and their variability-a crucial element for food security and resource allocation planning. These synthetic indicators are quantified by means of a probabilistic description of the soil water balance and crop development. The model results allow the interpretation of patterns of water productivity observed in Zea mays (maize) and Triticum aestivum (wheat), grown under a variety of soils, climates, and irrigation strategies. Employing the same modeling framework, the impact of rainfall pattern and irrigation strategy on yield and water requirements is further explored. The obtained standard deviations of yield and water requirements suggest the existence of a nonlinear tradeoff between yield stabilization and variability of water requirements, which in turn is strongly impacted by irrigation strategy. Moreover, intermediate rainfall amounts are associated to the highest variability in yields and irrigation requirements, although allowing the maximum water productivity. The existence of these tradeoffs between productivity, reliability, and sustainability poses a problem for water management, in particular in mesic climates. PMID- 25124767 TI - When learners surpass their models: mathematical modeling of learning from an inconsistent source. AB - It has been reported in the literature that both adults and children can, to a different degree, modify and regularize the often-inconsistent linguistic input they receive. We present a new algorithm to model and investigate the learning process of a learner mastering a set of (grammatical or lexical) forms from an inconsistent source. The algorithm is related to reinforcement learning and drift diffusion models of decision making, and possesses several psychologically relevant properties such as fidelity, robustness, discounting, and computational simplicity. It demonstrates how a learner can successfully learn from or even surpass its imperfect source. We use the data collected by Singleton and Newport (Cognit Psychol 49(4):370-407, 2004) on the performance of a 7-year-boy Simon, who mastered the American Sign Language (ASL) by learning it from his parents, both of whom were imperfect speakers of ASL. We show that the algorithm possesses a frequency boosting property, whereby the frequency of the most common form of the source is increased by the learner. We also explain several key features of Simon's ASL. PMID- 25124768 TI - Serum LDL cholesterol levels and new onset of arterial hypertension: an 8-year follow-up. AB - BACKGROUND: Serum cholesterol has been demonstrated to correlate with blood pressure values; therefore, abnormal levels of serum cholesterol might contribute to the development of hypertension. The aim of this study was to assess the new onset of hypertension over a period of 8 years in a pharmacologically untreated population sample in normo- and hypercholesterolemic individuals. DESIGN: 1864 Caucasian subjects with baseline blood pressure values <140/90 mmHg were subdivided into two different groups, according to LDL cholesterol changes observed over a period of 8 years. Group 1 included subjects whose LDL cholesterol levels remained or decreased within the normal range, while Group 2 included those whose LDL cholesterol levels were persistently increased above the normal range. The 8-year incidence of new-onset hypertension was 7.1% in Group 1 and 13.8% in Group 2 (P = 0.02), after adjustment for the main confounding risk factors. The difference between Groups 1 and 2 was confirmed in men (8.2 vs. 13.1%, P = 0.04) and women (6.1. vs. 14.5%, P = 006), as well as in subjects younger than 65 years (5.7 vs. 10.9%; P = 0.011), but not in older ones. CONCLUSIONS: Baseline serum LDL cholesterol levels are related to the rate of new onset hypertension in patients with normal or marginally elevated blood pressure values. PMID- 25124769 TI - Cervical internal carotid artery pseudoaneurysm complicating malignant otitis externa: first case report. AB - Pseudoaneurysm of the internal carotid artery (ICA) is a rare complication of head and neck infections. To date, three cases of petrous ICA pseudoaneurysm have been described as a complication of otogenic infection, including only one secondary to malignant otitis externa. We present here the first case of cervical ICA pseudoaneurysm as a complication of malignant otitis externa, and stress the importance of timely diagnosis to avoid fatal outcomes. PMID- 25124771 TI - Are 20 human papillomavirus types causing cervical cancer? AB - In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the alpha-Papillomaviridae, in particular to the species alpha5 (HPV51), alpha6 (HPV56), alpha7 (HPV18, HPV39, HPV45, HPV59) and alpha9 (HPV16, HPV31, HPV33, HPV35, HPV52, HPV58). Less evidence is available for a thirteenth type (HPV68, alpha7), which is classified as a 2A carcinogen (probably carcinogenic). Moreover, seven other phylogenetically related types (HPV26, HPV53, HPV66, HPV67, HPV68, HPV70 and HPV73) were identified as single HPV infections in certain rare cases of cervical cancer and were considered possibly carcinogenic (2B carcinogens). Recently, Halec et al [7] demonstrated that the molecular signature of HPV-induced carcinogenesis (presence of type-specific spliced E6*| mRNA; increased expression of p16; and decreased expression of cyclin D1, p53 and Rb) was similar in cervical cancers containing single infections with one of the eight afore-mentioned 2A or 2B carcinogens to those in cancers with single infections with group 1 carcinogens. Ninety six percent of cervical cancers are attributable to one of the 13 most common HPV types (groups 1 and 2A). Including the additional seven HPV types (group 2B) added 2.6%, to reach a total of 98.7% of all HPV-positive cervical cancers. From recently updated meta-analyses, it was shown that HPV68, HPV26, HPV66, HPV67, HPV73 and HPV82 were significantly more common in cancer cases than in women with normal cervical cytology, suggesting that for these HPV types, an upgrading of the carcinogen classification could be considered. However, there is no need to include them in HPV screening tests or vaccines, given their rarity in cervical cancers. PMID- 25124770 TI - Differential expression of Toll-like receptors and inflammatory cytokines in ovine interdigital dermatitis and footrot. AB - Footrot is a common inflammatory bacterial disease affecting the health and welfare of sheep worldwide. The pathogenesis of footrot is complex and multifactorial. The primary causal pathogen is the anaerobic bacterium Dichelobacter nodosus, with Fusobacterium necrophorum also shown to play a key role in disease. Since immune-mediated pathology is implicated, the aim of this research was to investigate the role of the host response in interdigital dermatitis (ID) and footrot. We compared the expression of Toll-like receptors (TLRs) and pro-inflammatory cytokines and the histological appearance of clinically normal in comparison to ID and footrot affected tissues. Severe ID and footrot were characterised by significantly increased transcript levels of pro inflammatory cytokines TNFalpha and IL1beta and the pattern recognition receptors TLR2 and TLR4 in the interdigital skin. This was reflected in the histopathological appearance, with ID and footrot presenting progressive chronic active pododermatitis with a mixed lymphocytic and neutrophilic infiltration, gradually increasing from a mild form in clinically normal feet, to moderate in ID and to a focally severe form with frequent areas of purulence in footrot. Stimulation with F. necrophorum and/or D. nodosus extracts demonstrated that dermal fibroblasts, the resident cell type of the dermis, also contribute to the inflammatory response to footrot bacteria by increased expression of TNFalpha, IL1beta and TLR2. Overall, ID and footrot lead to a local inflammatory response given that expression levels of TLRs and IL1beta were dependent on the disease state of the foot not the animal. PMID- 25124772 TI - Different distributions of preproMCH and hypocretin/orexin in the forebrain of the pig (Sus scrofa domesticus). AB - Neurons producing melanin-concentrating hormone (MCH) or hypocretin/orexin (Hcrt) have been implicated in the sleep/wake cycle and feeding behavior. Sleep and feeding habits vary greatly among mammalian species, depending in part of the prey/predatory status of animals. However, the distribution of both peptides has been described in only a limited number of species. In this work, we describe the distribution of MCH neurons in the brain of the domestic pig. Using in situ hybridization and immunohistochemistry, their cell bodies are shown to be located in the posterior lateral hypothalamic area (LHA), as expected. They form a dense cluster ventro-lateral to the fornix while only scattered cells are present dorsal to this tract. By comparison, Hcrt cell bodies are located mainly dorsal to the fornix. Therefore, the two populations of neurons display complementary distributions in the posterior LHA. MCH projections are, as indicated by MCH positive axons, very abundant in all cortical fields ventral to the rhinal sulcus, as well as in the lateral, basolateral and basomedial amygdala. In contrast, most of the isocortex is sparsely innervated. To conclude, the distribution of MCH cell bodies and projections shows some very specific features in the pig brain, that are clearly different of that described in the rat, mouse or human. In contrast, the Hcrt pattern seems more similar to that in these species, i.e. more conserved. These results suggest that the LHA anatomic organization shows some very significant interspecies differences, which may be related to the different behavioral repertoires of animals with regard to feeding and sleep/wake cycles. PMID- 25124773 TI - Radiographic analysis of the restoration of hip joint center following open reduction and internal fixation of acetabular fractures: a retrospective cohort study. AB - BACKGROUND: Unfavorable reduction is considered one of the key factors leading to joint degeneration and compromised clinical outcome in acetabular fracture patients. Besides the columns, walls, and superior dome, the postoperative position of hip joint center (HJC), which is reported to affect hip biomechanics, should be considered during the assessment of quality of reduction. We aimed to evaluate the radiographic restoration of HJC in acetabular fractures treated with open reduction and internal fixation. METHODS: Patients with a displaced acetabular fracture that received open reduction and internal fixation in the authors' institution during the past five years were identified from the trauma database. The horizontal and vertical shifts of HJC were measured in the standard anteroposterior view radiographs taken postoperatively. The radiographic quality of fracture reduction was graded according to Matta's criteria. The relationships between the shift of HJC and the other variables were evaluated. RESULTS: Totally 127 patients with 56 elementary and 71 associated-type acetabular fractures were included, wherein the majority showed a medial (89.0%) and proximal (93.7%) shift of HJC postoperatively. An average of 2.8 mm horizontal and 2.2 mm vertical shift of HJC were observed, which correlated significantly with the quality of fracture reduction (P < 0.001 for both). The horizontal shift of HJC correlated with the fracture type (P = 0.022). CONCLUSIONS: The restoration of HJC correlates with the quality of reduction in acetabular fractures following open reduction and internal fixation. Further studies are required to address the effects of HJC shift on the biomechanical changes and clinical outcomes of hip joint, especially in poorly reduced acetabular fractures. PMID- 25124776 TI - The neural correlates of cognitive behavioral therapy: recent progress in the investigation of patients with panic disorder. AB - Cognitive behavioral therapy (CBT) is an evidence-based treatment for mental disorders. Several meta-analytical reviews supported its efficacy and effectiveness in the treatment of panic disorder with agoraphobia (PD/AG). Recently, it has been shown that neurobiological changes are associated with the process and outcome of CBT. However, the general and specific neurobiological effects of CBT are still widely unknown. Therefore, the potential of applying neuroscience to clinical practice and optimizing CBT is still limited. The current review summarizes recent findings about the neural correlates of CBT in PD/AG measured with fMRI. Furthermore, the current review will focus on neural activation patterns predicting and moderating therapeutic success of CBT, due to its potential application in personalized treatment in the future. Finally, we will discuss some future perspectives of the neurosciences in CBT research. PMID- 25124777 TI - Novel insights related to CF neutrophils. PMID- 25124778 TI - Oral therapy for multiple myeloma: ixazomib arriving soon. PMID- 25124780 TI - Old and new news in CLL: "It's the pathway, stupid!". PMID- 25124779 TI - First do no harm: infectious deaths in pediatric ALL. PMID- 25124781 TI - A common progenitor cell in LCH and ECD. PMID- 25124782 TI - Is JAK2V617F finally off the hook? PMID- 25124783 TI - A step forward back to (induced) fetal. PMID- 25124784 TI - Less (bacterial diversity) is more (deaths). PMID- 25124786 TI - Activation of TRKB receptor in murine hematopoietic stem/progenitor cells induced mastocytosis. PMID- 25124785 TI - Blood collection methods affect cellular protein integrity: implications for clinical trial biomarkers and ZAP-70 in CLL. PMID- 25124787 TI - Engraftment of donor cells with germ-line integration of HHV6 mimics HHV6 reactivation following cord blood/haplo transplantation. PMID- 25124788 TI - Inhibition of neutrophil-dependent cytotoxicity for human endothelial cells by ACE inhibitors. AB - Angiotensin-converting enzyme inhibitors (ACEi) have immunomodulating properties and have been suggested to protect against endothelial injury, for example myocardial infarction and reperfusion injury. We tested whether two ACEi (captopril and enalapril), differing in a thiol group, protected human umbilical vein endothelial cells (HUVEC) from cytotoxicity induced by polymorphonuclear neutrophils (PMN) in vitro, when cells were activated by tumour necrosis factor alpha (TNFalpha) or the arachidonate derivative lipoxin-A4 (LXA4 ), using separate cytotoxicity pathways. When (51) Cr labelled HUVEC were treated with captopril (0-500 MUm) or enalapril (0-100 MUm) for 2 h and then activated by TNFalpha (100 ng/ml) for 24 h, a significant, dose-dependent reduction of (51) Cr release was observed. Similarly, captopril reduced (51) Cr release when LXA4 (0.1 MUm) was used to stimulate PMN for 4 h. Among previously defined mechanisms of significance for the cytotoxic reaction, expression of ICAM-1, but not intracellular Ca(2+) changes in PMN or PMN adherence to HUVEC, were reduced by ACEi treatment. Moreover, both ACEi inhibited HUVEC surface expression of TNFalpha receptor I (but not II). Thus, these ACEi, particularly captopril, interfere with PMN-induced cytotoxicity for endothelial cells by modulating pro inflammatory surface receptors, which is a novel effect that might be explored for further therapeutic approaches. PMID- 25124789 TI - Environmental costs and renewable energy: re-visiting the Environmental Kuznets Curve. AB - The environmental costs of economic development have received increasing attention during the last years. According to the World Energy Outlook (2013) sustainable energy policies should be promoted in order to spur economic growth and environmental protection in a global context, particularly in terms of reducing greenhouse gas emissions that contribute to climate change. Within this framework, the European Union aims to achieve the "20-20-20" targets, including a 20% reduction in EU greenhouse gas emissions from 1990 levels, a raise in the share of EU energy consumption produced from renewable resources to 20% and a 20% improvement in the EU's energy efficiency. Furthermore, the EU "Energy Roadmap 2050" has been recently adopted as a basis for developing a long-term European energy framework, fighting against climate change through the implementation of energy efficiency measures and the reduction of emissions. This paper focuses on the European context and attempts to explain the impact of economic growth on CO2 emissions through the estimation of an Environmental Kuznets Curve (EKC) using panel data. Moreover, since energy seems to be at the heart of the environmental problem it should also form the core of the solution, and therefore we provide some extensions of the EKC by including renewable energy sources as explanatory variables in the proposed models. Our data sets are referred to the 27 countries of the European Union during the period 1996-2010. With this information, our empirical results provide some interesting evidence about the significant impacts of renewable energies on CO2 emissions, suggesting the existence of an extended EKC. PMID- 25124790 TI - Capturing multiple values of ecosystem services shaped by environmental worldviews: a spatial analysis. AB - Two related approaches to valuing nature have been advanced in past research including the study of ecosystem services and psychological investigations of the factors that shape behavior. Stronger integration of the insights that emerge from these two lines of enquiry can more effectively sustain ecosystems, economies, and human well-being. Drawing on survey data collected from outdoor recreationists on Santa Cruz Island within Channel Islands National Park, U.S., our study blends these two research approaches to examine a range of tangible and intangible values of ecosystem services provided to stakeholders with differing biocentric and anthropocentric worldviews. We used Public Participation Geographic Information System methods to collect survey data and a Social Values for Ecosystem Services mapping application to spatially analyze a range of values assigned to terrestrial and aquatic ecosystems in the park. Our results showed that preferences for the provision of biological diversity, recreation, and scientific-based values of ecosystem services varied across a spatial gradient. We also observed differences that emerged from a comparison between survey subgroups defined by their worldviews. The implications emanating from this investigation aim to support environmental management decision-making in the context of protected areas. PMID- 25124791 TI - Candida glabrata endophthalmitis transmitted from graft to host after descemet stripping automated endothelial keratoplasty. PMID- 25124792 TI - Exploring the relationship between socioeconomic status and dog-bite injuries through spatial analysis. AB - INTRODUCTION: Despite a reported socioeconomic gradient in health, little is known about relationship between socioeconomic status (SES) and frequency of dog bite injuries. The primary objective of this study was to compare the frequency of dog-bite injuries, using data on dog-bite injury hospitalizations (DBIH), across different SES areas in Manitoba, Canada. The secondary objective of the study was to assess if frequency and pattern of DBIHs are similar to those of non canine bite injury hospitalizations (NCBIH) and rabies post-exposure prophylaxis (PEP). SES grouping in this study was defined through rurality and area-wide income quintile groups. METHODS: Rural and urban Manitoba neighbourhoods were ranked according to average area-level incomes into five levels (quintiles) with equal numbers of people in each income level. Prevalence was defined as the number of cases of hospitalizations (whether dog-bite injury or non-canine bite injury) or PEP reported in the years 1984-2006, divided by the total population during the same time period and expressed as the number of cases per 100 000 population per SES grouping. The 95% confidence intervals (CI) were calculated using the approach for Poisson distribution. RESULTS: During 1984-2006, Manitoba's prevalence (CI) of DBIH (3.19 (2.97, 3.41) per 100 000 population) was lower than prevalence of NCBIH (4.08 (3.84, 4.32)) and PEP (7.24 (6.92, 7.57)). Prevalence of DBIH was higher in rural than in urban areas (DBIH: 3.58 (3.24, 3.92) vs 2.87 (2.59, 3.15), p<0.01) and higher in the lowest income quintile areas than in the highest, whether rural (5.18 (4.24, 6.26) vs 3.29 (2.55, 4.17), p<0.0001) or urban (3.65 (2.97, 4.44) vs 2.24 (1.73, 2.87), p<0.01). The patterns of relationship between SES (rurality and income levels) and prevalence of NCBIH and PEP were similar to those between SES and DBIH. CONCLUSIONS: Although only a descriptive study, the results suggest that policies for control of dog-bite injuries should be area-specific. Prevention efforts could perhaps be improved by focussing not only on families, but also on neighbourhood regions. PMID- 25124793 TI - Dynamic respiratory endoscopic findings pre- and post laryngoplasty in Thoroughbred racehorses. AB - REASONS FOR PERFORMING STUDY: To investigate laryngeal function in cases of recurrent laryngeal neuropathy pre- and post laryngoplasty (LP) using dynamic respiratory endoscopy (DRE). OBJECTIVES: To compare the rima glottidis area during DRE pre- and post LP; document all forms of dynamic upper airway obstruction (DUAO) pre- and post LP and investigate the relationship between post operative abduction at rest and exercise. STUDY DESIGN: Prospective case series. METHODS: Thoroughbred racehorses with pre- and post LP DRE were included. Left-to right arytenoid cartilage angle ratios and rima glottidis area ratios were used to quantify laryngeal function during rest and exercise, pre- and post LP. RESULTS: In 35 horses, mean pre-LP ratios were greater during rest (left-to-right quotient angle ratio [LRQ] 0.76 +/- 0.13; left-to-right arytenoid ratio [LRR] 0.72 +/- 0.14; rima glottidis area ratio [RGA] 0.40 +/- 0.10) than exercise (LRQ 0.39 +/- 0.16, P < 0.001; LRR 0.38 +/- 0.16, P < 0.001; RGA 0.15 +/- 0.05, P < 0.001). Exercising ratios were larger post LP (LRQ 0.61 +/- 0.13; LRR 0.60 +/- 0.12; RGA 0.30 +/- 0.08) than pre-LP (LRQ 0.39 +/- 0.16, P < 0.001; LRR 0.38 +/- 0.16, P < 0.001; RGA 0.15 +/- 0.05, P < 0.001). A positive linear relationship was found between post LP resting and exercising ratios (R(2) = 0.48; P < 0.001) and post operative abduction grades (R(2) = 0.63; P < 0.001). Pre-LP all horses demonstrated left arytenoid cartilage collapse with bilateral vocal cord collapse and 37% had aryepiglottic fold collapse. Post LP 13 horses (37%) developed additional DUAOs and these horses had smaller RGAs (0.25 +/- 0.08) than horses that did not develop DUAOs (0.32 +/- 0.07, P = 0.01). CONCLUSIONS: Multiple forms of DUAO occurred pre-LP and additional forms often developed post LP. Post LP the degree of arytenoid cartilage abduction at rest was useful to predict the degree of abduction during exercise. PMID- 25124795 TI - Intriguing manipulation of metal-enhanced fluorescence for the detection of Cu(II) and cysteine. AB - Commercially available salicylaldehyde, in alkaline medium, exhibits strong fluorescence after one hour of UV exposure in the presence of Ag(I) . The phenolic group of salicylaldehyde is converted into the quinone form under alkaline conditions in the presence of AgNO3 , resulting in aggregated Ag(0), which causes approximately 250 times fluorescence enhancement of the in situ produced quinone. Such high silver-enhanced-fluorescence (SEF) is selectively quenched by cysteine, arginine, histidine, methionine, and tryptophan. In contrast to the other amino acids, ageing brings selectivity of the cysteine induced quenching effect. Interestingly, Cu(II) is found to be the only metal ion that exclusively regenerates the lost fluorescence. Thus, quenching and recovery of fluorescence (Turn Off/On) can be used for the selective and sensitive detection of cysteine as well as Cu(II) ions in one pot. Alteration of the electric field density around the fluorophore (lightening rod effect) and scattering/absorption cross-section have been proposed to account for the Off/On fluorescence. PMID- 25124794 TI - Serum immunoglobulin E and interleukin-13 levels in children with idiopathic nephrotic syndrome. AB - Serum IgE and IL-13 levels were estimated in 40 idiopathic nephrotic syndrome and 16 controls. There were 15 first episode nephrotic syndrome (FENS), 15 infrequent relapsing nephrotic syndrome (IRNS) and 10 patients belonged to frequent relapsing nephrotic syndrome (FRNS). Serum IgE and IL-13 levels were significantly increased in active nephrotic syndrome and its sub-groups as compared to controls and remission (p < 0.001). IgE levels did not differ significantly among different subgroups, while Il-13 was significantly higher in FRNS in comparison with FENS (p = 0.041). Both IgE and IL-13 levels were comparable in nephrotic patients with and without bronchial asthma. Serum IL-13 had significant positive correlation with IgE (r = 0.605, p < 0.001). Thus, raised levels of IgE and IL-13 are found in nephrotic syndrome and could have a role in the pathogenesis of disease. PMID- 25124797 TI - Plane-wave density functional theory investigation of adsorption of 2,4,6 trinitrotoluene on Al-hydroxylated (0001) surface of (4 * 4) alpha-alumina. AB - This article reports the results of the theoretical investigation of adsorption of 2,4,6-trinitrotoluene (TNT) on Al-hydroxylated (0001) surface of (4 * 4) alpha alumina (alpha-Al2O3) using plane-wave Density Functional Theory. Sixteen water molecules were used to hydroxylate the alumina surface. The Perdew-Burke Ernzerhof functional and the recently developed van der Waals functional (vdW DF2) were used. The interaction of electron with core was accounted using the Vanderbilt ultrasoft pseudopotentials. It was found that hydroxylation has significant influence on the geometry of alumina and such changes are prominent up to few layers from the surface. Particularly, due to the Al-hydroxylation the oxygen layers are decomposed into sublayers and such partitioning becomes progressively weaker for interior layers. Moreover, the nature of TNT adsorption interaction is changed from covalent type on the pristine alumina surface to hydrogen-bonding interaction on the Al-hydroxylated alumina surface. TNT in parallel orientation forms several hydrogen bonds compared to that in the perpendicular orientation with hydroxyl groups of the Al-hydroxylated alumina surface. Therefore, the parallel orientation will be present in the adsorption of TNT on Al-hydroxylated (0001) surface of alpha-alumina. Further, the vdW-DF2 van der Waals functional was found to be most suitable and should be used for such surface adsorption investigation. PMID- 25124796 TI - Snail regulated by PKC/GSK-3beta pathway is crucial for EGF-induced epithelial mesenchymal transition (EMT) of cancer cells. AB - Cancer metastasis is considered a major challenge in cancer therapy. Recently, epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling has been shown to induce epithelial-mesenchymal transition (EMT) and thereby to promote cancer metastasis. However, the underlying mechanism has not been fully elucidated. We demonstrate that EGF can induce EMT in human prostate and lung cancer cells and thus promote invasion and migration. EGF-induced EMT has been characterized by the cells acquiring mesenchymal spindle-like morphology and increasing their expression of N-cadherin and fibronectin, with a concomitant decrease of E-cadherin. Both protein and mRNA expression of transcription factor Snail rapidly increases after EGF treatment. The knockdown of Snail significantly attenuates EGF-induced EMT, suggesting that Snail is crucial for this process. To determine the way that Snail is accumulated, we demonstrate (1) that EGF promotes the stability of Snail via inhibiting the activity of glycogen synthase kinase 3 beta (GSK-3beta), (2) that protein kinase C (PKC) rather than the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is responsible for GSK-3beta inhibition and (3) that GSK-3beta inhibition promotes the transcription of Snail. Taken together, these results reveal that the PKC/GSK 3beta signaling pathway controls both the stability and transcription of Snail, which is crucial for EMT induced by EGF in PC-3 and A549 cells. Our study suggests a novel signaling pathway for Snail regulation and provides a better understanding of growth-factor-induced tumor EMT and metastasis. PMID- 25124801 TI - Advanced drug delivery systems for therapeutic applications. PMID- 25124804 TI - Phenotypic plasticity and similarity among gall morphotypes on a superhost, Baccharis reticularia (Asteraceae). AB - Understanding factors that modulate plant development is still a challenging task in plant biology. Although research has highlighted the role of abiotic and biotic factors in determining final plant structure, we know little of how these factors combine to produce specific developmental patterns. Here, we studied patterns of cell and tissue organisation in galled and non-galled organs of Baccharis reticularia, a Neotropical shrub that hosts over ten species of galling insects. We employed qualitative and quantitative approaches to understand patterns of growth and differentiation in its four most abundant gall morphotypes. We compared two leaf galls induced by sap-sucking Hemiptera and stem galls induced by a Lepidopteran and a Dipteran, Cecidomyiidae. The hypotheses tested were: (i) the more complex the galls, the more distinct they are from their non-galled host; (ii) galls induced on less plastic host organs, e.g. stems, develop under more morphogenetic constraints and, therefore, should be more similar among themselves than galls induced on more plastic organs. We also evaluated the plant sex preference of gall-inducing insects for oviposition. Simple galls were qualitative and quantitatively more similar to non-galled organs than complex galls, thereby supporting the first hypothesis. Unexpectedly, stem galls had more similarities between them than to their host organ, hence only partially supporting the second hypothesis. Similarity among stem galls may be caused by the restrictive pattern of host stems. The opposite trend was observed for host leaves, which generate either similar or distinct gall morphotypes due to their higher phenotypic plasticity. The Relative Distance of Plasticity Index for non-galled stems and stem galls ranged from 0.02 to 0.42. Our results strongly suggest that both tissue plasticity and gall inducer identity interact to determine plant developmental patterns, and therefore, final gall structure. PMID- 25124805 TI - Assessment of 5-fluorouracil and 4-nitroquinoline-1-oxide in vivo genotoxicity with Pig-a mutation and micronucleus endpoints. AB - Genotoxicity assessments were conducted on male Sprague Dawley rats treated with 5-fluorouracil (5-FU) and 4-nitroquinoline-1-oxide (4NQO) as part of an international validation trial of the Pig-a mutant phenotype assay. Rats were orally exposed to 0, 11.5, 23, or 46 mg/kg/day 5-FU for three consecutive days (Days 1-3); blood was sampled on Days -1, 4, 15, 29, and 45. Pig-a mutant phenotype reticulocyte (RET(CD59-)) and mutant phenotype erythrocyte (RBC(CD59-)) frequencies were determined on Days -1, 15, 29, and 45, and percent micronucleated reticulocytes (%MN-RET) were measured on Day 4. Rats were treated with 4NQO for 28 consecutive days by oral gavage, at doses of 1.5, 3, or 6 mg/kg/day. RBC(CD59-) and RET(CD59-) frequencies were determined on Days -1, 15, and 29, and MN-RET were quantified on Day 29. Whereas 5-FU was found to increase %MN-RET, no significant increases were observed for RBC(CD59-) or RET(CD59-) at any of the time points studied. The high dose of 4NQO (6 mg/kg/day) was observed to markedly increase RBC(CD59-) and RET(CD59-) frequencies, and this same dose level caused a weak but significantly elevated increase in MN-RET (approximately twofold). Collectively, the results provide additional support for the combination of Pig-a mutation and MN-RET into acute and 28-day repeat-dose studies. PMID- 25124806 TI - Feasibility study to assess clinical applications of 3-T cine MRI coupled with synchronous audio recording during speech in evaluation of velopharyngeal insufficiency in children. AB - BACKGROUND: In the past decade, there has been increased utilization of magnetic resonance imaging (MRI) in evaluating and understanding velopharyngeal insufficiency (VPI). To our knowledge, none of the prior studies with MRI has simultaneously linked the audio recordings of speech during cine MRI acquisition with the corresponding images and created a video for evaluating VPI. OBJECTIVE: To develop an MRI protocol with static and cine sequences during phonation to evaluate for VPI in children and compare the findings to nasopharyngoscopy and videofluoroscopy. MATERIALS AND METHODS: Five children, ages 8-16 years, with known VPI, who had previously undergone nasopharyngoscopy and videofluoroscopy, were included. MRI examination was performed on a 3-T Siemens scanner. Anatomical data was obtained using an isotropic T2-weighted 3-D SPACE sequence with multiplanar reformation capability. Dynamic data was obtained using 2-D FLASH cine sequences of the airway in three imaging planes during phonation. Audio recordings were captured by a MRI compatible optical microphone. RESULTS: All five cases had MRI and nasopharyngoscopy and four had videofluoroscopy performed. VPI was identified by MRI in all five patients. The location and severity of the velopharyngeal gap, closure pattern, velar size and shape and levator veli palatini (LVP) muscle were identified in all patients. MRI was superior in visualizing the integrity of the LVP muscle. MRI was unable to identify hemipalatal weakness in one case. In a case of stress-induced VPI, occurring only during clarinet playing, cine MRI demonstrated discordant findings of a velopharyngeal gap during phonatory tasks but not with instrument playing. Overall, there was satisfactory correlation among MRI, nasopharyngoscopy and videofluoroscopy findings. CONCLUSION: Cine MRI of the airway during speech is a noninvasive, well-tolerated diagnostic imaging tool that has the potential to serve as a guide prior to and after surgical correction of VPI. MRI provided superior anatomical detail of the levator musculature. The creation of a video with recorded phonation allowed correlation between palatal movements and specific phonatory tasks. PMID- 25124808 TI - 8-Azapurines as isosteric purine fluorescent probes for nucleic acid and enzymatic research. AB - The 8-azapurines, and their 7-deaza and 9-deaza congeners, represent a unique class of isosteric (isomorphic) analogues of the natural purines, frequently capable of substituting for the latter in many biochemical processes. Particularly interesting is their propensity to exhibit pH-dependent room temperature fluorescence in aqueous medium, and in non-polar media. We herein review the physico-chemical properties of this class of compounds, with particular emphasis on the fluorescence emission properties of their neutral and/or ionic species, which has led to their widespread use as fluorescent probes in enzymology, including enzymes involved in purine metabolism, agonists/antagonists of adenosine receptors, mechanisms of catalytic RNAs, RNA editing, etc. They are also exceptionally useful fluorescent probes for analytical and clinical applications in crude cell homogenates. PMID- 25124809 TI - Unexpected positive intraoperative cultures in aseptic revision arthroplasty. AB - Unexpected positive intraoperative cultures (UPIC) in presumed aseptic revision arthroplasty can be difficult to interpret. The purpose of this retrospective study was to compare the incidence of subsequent periprosthetic joint infection (PJI) in patients who received antibiotic therapy according to an institutional protocol with those who did not and whether they meet Musculoskeletal Infection Society (MSIS) criteria for PJI. In patients who were treated with antibiotic according to institutional criteria, the incidence of PJI after revision was higher in those who did not meet MSIS criteria (22%) than in those that met MSIS criteria (14%; P > 0.71). UPIC in aseptic revision arthroplasty are not uncommon. PJI cannot be excluded in patients that do not meet MSIS definition. PMID- 25124812 TI - Multiple populations of pantropical spotted dolphins in Hawaiian waters. AB - Understanding gene flow and dispersal patterns is important for predicting effects of natural events and anthropogenic activities on animal populations. In Hawaii, most species of odontocetes are managed as single populations. Recent exceptions include false killer whales, spinner dolphins, and common bottlenose dolphins, for which studies have shown fidelity to individual islands or groups of islands. Our study focused on pantropical spotted dolphins. We analyzed mitochondrial control region and 11 microsatellite loci from 101 individuals from 4 areas: Hawaii, Maui/Lanai, Oahu, and Kauai/Niihau. We examined F ST, F' ST, R ST, Jost's D, and PhiST and used TESS to estimate number of populations and assignment probabilities. Our results support genetic differentiation among Hawaii, Maui/Lanai, and Oahu and suggest that pantropical spotted dolphins near Kauai/Niihau are likely transient and in low numbers. Between island regions, F ST for microsatellites ranged from 0.016 to 0.045 and for mtDNA, from 0.011 to 0.282. F ' ST, ranged from 0.098 to 0.262 for microsatellites and 0.019 to 0.415 for mtDNA. R ST and PhiST showed similar results to F ST for microsatellites and mtDNA respectively, and Jost's D fell between F ST and F ' ST. TESS supported 3 populations, and greatest mean assignment probability by island region ranged from 0.50 to 0.72. The private alleles method indicated migration rates among regions from 1.49 to 3.45, and effective population size of the island of Hawaii was estimated to be 220. There was no strong evidence to support sex-biased dispersal or group fidelity. Considering this study in the larger context of other odontocete population studies and studies of connectivity, we suggest genetic differentiation may be mediated by behavior adapted to differing habitat types and niches. PMID- 25124813 TI - Contrasting levels of clonal and within-population genetic diversity between the 2 ecologically different herbs Polygonatum stenophyllum and Polygonatum inflatum (Liliaceae). AB - Comparative studies on clonal and genetic structure between ecologically contrasting congeners may provide valuable insights into the mechanisms promoting the maintenance of genetic diversity in clonal plant species. Polygonatum stenophyllum has long rhizomes (ca. 30-40 cm long) and largely occurs on sandy soils in open river banks, whereas its congener Polygonatum inflatum has short ones (ca. 5-10 cm long) and occurs on humic soils under deciduous forests. Using 21 allozyme loci, we comparatively assessed levels of clonal and genetic diversity in the 2 clonal species. Seven populations of P. stenophyllum consisted of single clones, and levels of within-population clonal and genetic variation were considerably lower than those of P. inflatum. However, when samples were pooled, P. stenophyllum harbored higher genetic variation than P. inflatum, which is due to higher among-population genetic differentiation in the former species compared with the latter (FST=0.636 vs. FST=0.165). Our data suggest that populations of P. stenophyllum have been mainly founded by a single seed or rhizome (through river water) or by a few seeds, whereas populations of P. inflatum would have been established through multiple, repeated seedling recruitment. Moderate levels of genetic diversity in a population of P. stenophyllum located at the foot of the Baekdudaegan Mountains and in all the populations of P. inflatum are consistent with the previous hypothesis that these mountains served as a glacial refugium for many boreal species of the Korean Peninsula. PMID- 25124814 TI - Outcomes of Fukushima: biological effects of radiation on nonhuman species. PMID- 25124807 TI - Cerebrospinal fluid markers of neuroinflammation in delirium: a role for interleukin-1beta in delirium after hip fracture. AB - OBJECTIVE: Exaggerated central nervous system (CNS) inflammatory responses to peripheral stressors may be implicated in delirium. This study hypothesised that the IL-1beta family is involved in delirium, predicting increased levels of interleukin-1beta (IL-1beta) and decreased IL-1 receptor antagonist (IL-1ra) in the cerebrospinal fluid (CSF) of elderly patients with acute hip fracture. We also hypothesised that Glial Fibrillary Acidic Protein (GFAP) and interferon gamma (IFN-gamma) would be increased, and insulin-like growth factor 1 (IGF-1) would be decreased. METHODS: Participants with acute hip fracture aged >60 (N=43) were assessed for delirium before and 3-4 days after surgery. CSF samples were taken at induction of spinal anaesthesia. Enzyme-linked immunosorbent assays (ELISA) were used for protein concentrations. RESULTS: Prevalent delirium was diagnosed in eight patients and incident delirium in 17 patients. CSF IL-1beta was higher in patients with incident delirium compared to never delirium (incident delirium 1.74 pg/ml (1.02-1.74) vs. prevalent 0.84 pg/ml (0.49-1.57) vs. never 0.66 pg/ml (0-1.02), Kruskal-Wallis p=0.03). CSF:serum IL-1beta ratios were higher in delirious than non-delirious patients. CSF IL-1ra was higher in prevalent delirium compared to incident delirium (prevalent delirium 70.75 pg/ml (65.63-73.01) vs. incident 31.06 pg/ml (28.12-35.15) vs. never 33.98 pg/ml (28.71 43.28), Kruskal-Wallis p=0.04). GFAP was not increased in delirium. IFN-gamma and IGF-1 were below the detection limit in CSF. CONCLUSION: This study provides novel evidence of CNS inflammation involving the IL-1beta family in delirium and suggests a rise in CSF IL-1beta early in delirium pathogenesis. Future larger CSF studies should examine the role of CNS inflammation in delirium and its sequelae. PMID- 25124811 TI - In vivo growth suppression of CT-26 mouse colorectal cancer cells by adenovirus expressed small hairpin RNA specifically targeting thymosin beta-4 mRNA. AB - Thymosin beta-4 (Tbeta4) is known to be involved in tumorigenesis. Overexpression of this polypeptide has been observed in a wide variety of cancers, including colorectal carcinoma (CRC). Accordingly, Tbeta4 has been proposed to be a novel therapeutic target for CRC, especially in its metastatic form. Although in vitro tumor-suppressive effects of Tbeta4 gene silencing mediated by small hairpin RNA (shRNA) have already been demonstrated, the in vivo efficacy of such an approach has not yet been reported. Herein, we demonstrated that infection with recombinant adenovirus expressing an shRNA targeting Tbeta4 markedly reduced the growth of and robustly induced apoptosis in CT-26 mouse CRC cells in culture. Additionally, tumors grown in nude mice from the CT-26 cells whose Tbeta4 expression already been downregulated by virus infection were also drastically reduced. Most importantly, significant growth arrest of tumors derived from the parental CT-26 cells was observed after multiple intratumoral injections of these viruses. Together, our results show for the first time that in vivo silencing of Tbeta4 expression by its shRNA generated after adenoviral infection can suppress CRC growth. These results further demonstrate the feasibility of treating CRC by a Tbeta4 knockdown gene therapeutic approach. PMID- 25124815 TI - Genetic and ecological studies of animals in Chernobyl and Fukushima. AB - Recent advances in genetic and ecological studies of wild animal populations in Chernobyl and Fukushima have demonstrated significant genetic, physiological, developmental, and fitness effects stemming from exposure to radioactive contaminants. The few genetic studies that have been conducted in Chernobyl generally show elevated rates of genetic damage and mutation rates. All major taxonomic groups investigated (i.e., birds, bees, butterflies, grasshoppers, dragonflies, spiders, mammals) displayed reduced population sizes in highly radioactive parts of the Chernobyl Exclusion Zone. In Fukushima, population censuses of birds, butterflies, and cicadas suggested that abundances were negatively impacted by exposure to radioactive contaminants, while other groups (e.g., dragonflies, grasshoppers, bees, spiders) showed no significant declines, at least during the first summer following the disaster. Insufficient information exists for groups other than insects and birds to assess effects on life history at this time. The differences observed between Fukushima and Chernobyl may reflect the different times of exposure and the significance of multigenerational mutation accumulation in Chernobyl compared to Fukushima. There was considerable variation among taxa in their apparent sensitivity to radiation and this reflects in part life history, physiology, behavior, and evolutionary history. Interestingly, for birds, population declines in Chernobyl can be predicted by historical mitochondrial DNA base-pair substitution rates that may reflect intrinsic DNA repair ability. PMID- 25124816 TI - Fukushima's biological impacts: the case of the pale grass blue butterfly. AB - To evaluate the effects of the Fukushima nuclear accident on the surrounding area, we studied the pale grass blue butterfly Zizeeria maha, the most common butterfly in Japan. We here review our important findings and their implications. We found forewing size reduction, growth retardation, high mortality rates, and high abnormality rates in the field and reared samples. The abnormality rates observed in September 2011 were higher than those observed in May 2011 in almost all localities, implying transgenerational accumulation of genetic damage. Some of the abnormal traits in the F1 generation were inherited by the F2 generation. In a particular cross, the F2 abnormality rate scored 57%. The forewing size reduction and high mortality and abnormality rates were reproduced in external and internal exposure experiments conducted in our laboratory using Okinawa larvae. We observed the possible real-time evolution of radiation resistance in the Fukushima butterflies, which, in retrospect, indicates that field sampling attempts at the very early stages of such accidents are required to understand the ecodynamics of polluted regions. We propose, as the postulates of pollutant induced biological impacts, that the collection of phenotypic data from the field and their relevant reproduction in the laboratory should be the basis of experimental design to demonstrate the biological effects of environmental pollutants and to investigate the molecular mechanisms responsible for these effects. PMID- 25124817 TI - Unraveling low-level gamma radiation--responsive changes in expression of early and late genes in leaves of rice seedlings at Iitate Village, Fukushima. AB - In the summer of 2012, 1 year after the nuclear accident in March 2011 at the Fukushima Daiichi nuclear power plant, we examined the effects of gamma radiation on rice at a highly contaminated field of Iitate village in Fukushima, Japan. We investigated the morphological and molecular changes on healthy rice seedlings exposed to continuous low-dose gamma radiation up to 4 uSv h(-1), about 80 times higher than natural background level. After exposure to gamma rays, expression profiles of selected genes involved in DNA replication/repair, oxidative stress, photosynthesis, and defense/stress functions were examined by RT-PCR, which revealed their differential expression in leaves in a time-dependent manner over 3 days (6, 12, 24, 48, and 72 h). For example, OsPCNA mRNA rapidly increased at 6, 12, and 24 h, suggesting that rice cells responded to radiation stress by activating a gene involved in DNA repair mechanisms. At 72 h, genes related to the phenylpropanoid pathway (OsPAL2) and cell death (OsPR1oa) were strongly induced, indicating activation of defense/stress responses. We next profiled the transcriptome using a customized rice whole-genome 4*44K DNA microarray at early (6h) and late (72 h) time periods. Low-level gamma radiation differentially regulated rice leaf gene expression (induced 4481 and suppressed 3740 at 6 h and induced 2291 and suppressed 1474 genes at 72 h) by at least 2-fold. Using the highly upregulated and downregulated gene list, MapMan bioinformatics tool generated diagrams of early and late pathways operating in cells responding to gamma ray exposure. An inventory of a large number of gamma radiation-responsive genes provides new information on novel regulatory processes in rice. PMID- 25124824 TI - Exploring associations between lower urinary tract symptoms (LUTS) and gastrointestinal (GI) problems in women: a study in women with urological and GI problems vs a control population. AB - OBJECTIVES: To study the prevalence of self-reported lower urinary tract symptoms (LUTS) in women consulting a Gastroenterology clinic with complaints of functional constipation (FC), fecal incontinence (FI) or both, compared with a female control population. Also, to study the influence of FC, FI, or both on self-reported LUTS in women attending a Urology clinic. PATIENTS AND METHODS: We present a retrospective study of data collected through a validated self administered bladder and bowel symptom questionnaire in a tertiary referral hospital from three different female populations: 104 controls, 159 gastroenterological patients and 410 urological patients. Based on the reported bowel symptoms, patients were classified as having FC, FI, a combination of both, or, no FC or FI. LUTS were compared between the control population and the gastroenterological patients, and between urological patients with and without concomitant gastroenterological complaints. Results were corrected for possible confounders through logistic regression analysis. RESULTS: The prevalence of LUTS in the control population was similar to large population-based studies. Nocturia was significantly more prevalent in gastroenterological patients with FI compared with the control population [odds ratio (OR) 9.1]. Female gastroenterological patients with FC more often reported straining to void (OR 10.3), intermittency (OR 5.5), need to immediately re-void (OR 3.7) and feeling of incomplete emptying (OR 10.5) compared with the control population. In urological patients, urgency (94%) and urgency urinary incontinence (UUI, 54% of UI) were reported more often by patients with FI than by patients without gastroenterological complaints (58% and 30% of UI respectively), whereas intermittency (OR 3.6), need to immediately re-void (OR 2.2) and feeling of incomplete emptying (OR 2.2) were reported more often by patients with FC than by patients without gastroenterological complaints. CONCLUSION: As LUTS are reported significantly more often by female gastroenterological patients than by a control population, and as there is a difference in self-reported LUTS between female urological patients with different concomitant gastroenterological complaints, we suggest that general practitioners, gastroenterologists and urologists should always include the assessment of symptoms of the other pelvic organ system in their patient evaluation. The clinical correlations between bowel symptoms and LUTS may be explained by underlying neurological mechanisms. PMID- 25124823 TI - Pachyonychia congenita cornered: report on the 11th Annual International Pachyonychia Congenita Consortium Meeting. AB - This is a report of the research presented at the 11th Annual Meeting of the International Pachyonychia Congenita Consortium, held on 6 May 2014 in Albuquerque, NM, U.S.A. This year's meeting was divided into five corners concerning pachyonychia congenita (PC) research: (i) 'PC Pathogenesis Cornered', an overview of recent keratin research, for PC and other skin disorders; (ii) 'From All Corners of ...', an outline of other genetic disorders that we can learn from; (iii) 'Fighting For Our Corner', an outline of National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases programmes and U.S. funding opportunities applicable to rare skin disorders; (iv) 'The PC Corner', focusing on recent clinical studies related to PC; and (v) 'Clinical Corners: Turning the Corner?', an update on ongoing PC clinical trials. PMID- 25124825 TI - The effect of beta blocker withdrawal on adenosine myocardial perfusion imaging. AB - BACKGROUND: The effect of beta blockers on myocardial blood flow (MBF) under vasodilators has been studied in several SPECT and PET myocardial perfusion imaging (MPI) studies with divergent results. The present study evaluated the effect of a beta blocker withdrawal on quantitative adenosine MBF and on MPI results. METHODS: Twenty patients with beta blockers and CAD history were studied with quantitative adenosine N-13 ammonia PET. The first study was performed under complete medication and the second after beta blocker withdrawal. The PET studies were independently read with respect to MPI result and clinical decision making. RESULTS: Global MBF showed an increase from 180.2 +/- 59.9 to 193.6 +/- 60.8 mL.minute(-1)/100 g (P = .02) after beta blocker withdrawal. The segmental perfusion values were closely correlated (R(2) = 0.82) over the entire range of perfusion values. An essentially different interpretation after beta blocker discontinuation was found in two cases (10%). CONCLUSION: A beta blocker withdrawal induces an increase in adenosine MBF. In the majority of cases, MPI interpretation and decision making are independent of beta blocker intake. If a temporary beta blocker withdrawal before MPI is not possible or was not realized by the patient, it is appropriate to perform adenosine stress testing without loss of the essential MPI result. PMID- 25124828 TI - Does risk for major adverse cardiac events in patients undergoing vasodilator stress with adjunctive exercise differ from patients undergoing either standard exercise or vasodilator stress with myocardial perfusion imaging? AB - BACKGROUND: In patients with functional limitations, the use of adjunctive exercise with vasodilator stress has advantages over vasodilator stress alone in single photon emission computed tomography myocardial perfusion imaging (MPI) for technical reasons and with regards to more effective cardiac risk stratification. Whether patients who undergo vasodilator with adjunctive exercise stress MPI possess clinical characteristics and cardiac risk that differs from those who undergo standard exercise or vasodilator stress MPI is unknown. METHODS: Prospectively collected data on 19,367 consecutive patients referred for stress MPI to a tertiary care center (9,331 [48%] underwent exercise-only, 3,793 [20%] underwent vasodilator plus exercise, and 6,243 [32%] underwent vasodilator-only) were analyzed. Perfusion data were scored using the ASNC 17-segment with a summed stress score (SSS) < 4 = normal, 4-8 = mildly abnormal, and > 8 = moderate to severely abnormal. Patients were followed a mean of 1.96 +/- 0.95 years. Demographics, clinical characteristics, and the occurrence of major adverse cardiac events (cardiac death or nonfatal myocardial infarction) were compared between the three stress modality groups. RESULTS: Comparison of demographics and clinical characteristics revealed significant differences in gender, age, cardiac risk factors, and stress MPI between the three stress modality groups (P < .001). In follow-up, cardiac event-free survival of patients in the vasodilator plus exercise stress group was significantly higher than those in the vasodilator-only group but lower than those in the exercise-only group (P < .001). Annualized cardiac event rates of patients in the vasodilator plus exercise stress group were significantly lower than those in the vasodilator-only group for all three categories of the SSS (P < .001). After multivariable adjustment, with exercise only as reference category, vasodilator plus exercise and vasodilator-only stress emerged as independent predictors (more likely occurrence) of cardiac death, while vasodilator-only stress emerged as an independent predictor (more likely occurrence) of cardiac death or nonfatal myocardial infarction. With vasodilator only as the reference category, exercise-only and vasodilator plus exercise stress emerged as independent predictors (less likely occurrence) of cardiac death as well as of cardiac death or nonfatal myocardial infarction. CONCLUSIONS: Patients undergoing vasodilator plus exercise stress MPI possess clinical characteristics and cardiac risk that differs significantly from those undergoing either standard exercise or vasodilator stress MPI and places them in a lower risk category compared to vasodilator stress alone. PMID- 25124826 TI - Comparison of Tc-99m tetrofosmin myocardial perfusion scintigraphy and exercise F18-FDG imaging in detection of myocardial ischemia in patients with coronary artery disease. AB - BACKGROUND: Direct ischemia imaging with F18-FDG can potentially overcome many limitations of SPECT-MPS inherent to "cold imaging". We compared SPECT-MPS with exercise F18-FDG PET in detection of ischemia in patients with suspected CAD. METHODS: 45 patients with clinical suspicion of CAD without the history of myocardial infarction were prospectively included. All patients underwent Tc-99m tetrofosmin SPECT-MPS and exercise F18-FDG PET imaging within 7 days of SPECT MPS, and both modalities were compared with coronary angiography for detecting ischemia. RESULTS: 27 patients had an abnormal coronary angiography (at least one coronary artery with stenosis >50%). Exercise F18-FDG performed better than SPECT MPS in LAD and LCX territory with comparably good performance in RCA territory. Exercise F18-FDG performed better in single-vessel disease and equally good in multi-vessel disease compared to SPECT-MPS. Performance of exercise 18F-FDG study was significantly better than SPECT-MPS (P = .0014) in the analysis of the 81 vascular territories in the 27 patients with abnormal coronary angiography. Performance of exercise F18-FDG was significantly better than SPECT-MPS in detecting ischemia in suspected CAD patients. CONCLUSION: Exercise F18-FDG imaging is a potentially useful ischemia imaging modality which offers the advantages of direct ischemia imaging in CAD patients. PMID- 25124827 TI - Molecular imaging of plaque vulnerability. AB - Over the past decade, significant progress has been made in the development of novel imaging strategies focusing on the biology of the vessel wall for identification of vulnerable plaques. While the majority of these studies are still in the pre-clinical stage, few techniques (e.g., (18)F-FDG and (18)F-NaF PET imaging) have already been evaluated in clinical studies with promising results. Here, we will briefly review the pathobiology of atherosclerosis and discuss molecular imaging strategies that have been developed to target these events, with an emphasis on mechanisms that are associated with atherosclerotic plaque vulnerability. PMID- 25124830 TI - Synthesis of highly active and stable spinel-type oxygen evolution electrocatalysts by a rapid inorganic self-templating method. AB - Composition-adjustable spinel-type metal oxides, Mnx Co3-x O4-delta (x=0.8-1.4), were synthesized in ethanol solutions by a rapid inorganic self-templating mechanism using KCl nanocrystals as the structure-directing agent. The Mnx Co3?x O4?delta materials showed ultrahigh oxygen evolution activity and strong durability in alkaline solutions, and are capable of delivering a current density of 10 mA cm(-2) at 1.58 V versus the reversible hydrogen electrode in 0.1 M KOH solution, which is superior in comparison to IrO2 catalysts under identical experimental conditions, and comparable to the most active noble-metal and transition-metal oxygen evolution electrocatalysts reported so far. The high performance for catalytic oxygen evolution originates from both compositional and structural features of the synthesized materials. The moderate content of Mn doping into the spinel framework led to their improved electronic conductivity and strong oxidizing ability, and the well-developed porosity, accompanied with the high affinity between OH(-) reactants and catalyst surface, contributed to the smooth mass transport, thus endowing them with superior oxygen evolution activity. PMID- 25124829 TI - Treatment failure in cognitive-behavioural therapy: therapeutic alliance as a precondition for an adherent and competent implementation of techniques. AB - OBJECTIVES: Treatment failure is a common phenomenon, but little is known about the reasons. Therapeutic alliance, therapist adherence, and therapist competence are considered important aspects of treatment success and formed the focus of the current investigation. DESIGN: Three randomized controlled trials for the treatment of depression, social phobia, and hypochondriasis were the basis of the current study. METHODS: The role of therapeutic alliance, as well as therapist adherence and competence, were investigated in 61 patients, which were classified either as treatment failure or as treatment success. Process variables were evaluated by independent raters on the basis of videotapes of the first three treatment sessions. RESULTS: Therapists' adherence and therapeutic alliance differed significantly between successful treatments and those classified as failures, whereas therapists' competence did not. In cross-sectional analysis, we found a moderating effect of adherence with alliance on treatment outcome, indicating that the better the therapeutic alliance, the stronger the effect of adherence on treatment outcome. Moreover, higher therapists' competence was found to affect treatment outcome positively, only mediated by therapeutic alliance. Higher therapists' adherence affected treatment outcome positively, only mediated by the competence-alliance relationship. In additional longitudinal analyses, we found evidence that the therapeutic alliance within one session influences therapists' adherence and competence in the subsequent session, but not the other way around. CONCLUSIONS: Therapeutic alliance proved to be an important variable for the prediction of treatment failure. Furthermore, in our longitudinal analyses, we found evidence that the therapeutic alliance is a precondition for the adherent and competent implementation of therapeutic techniques, which questions the results of our cross-sectional analysis and of previous research. PRACTITIONER POINTS: Clinical implications Treatment failure is associated with a lower therapeutic alliance in cognitive-behavioural treatment. Therapeutic alliance seems to be an important precondition for the adherent and competent implementation of therapeutic techniques. Therapeutic alliance should be monitored during psychotherapeutic treatment. Cautions or limitations Results are limited to cognitive-behavioural therapy and may not be representative for other treatment approaches. Process analyses are based on highly standardized randomized controlled trials and may not be generalizable to routine care. PMID- 25124831 TI - Socio-economic determinants of ownership and use of treated bed nets in Nigeria: results from a cross-sectional study in Cross River and Bauchi States in 2011. AB - BACKGROUND: Poor people bear a disproportionate burden of malaria and prevention measures may not reach them well. A study carried out to examine the socio economic factors associated with ownership and use of treated bed nets in Cross River and Bauchi States of Nigeria took place soon after campaigns to distribute treated bed nets. METHODS: A cross-sectional household survey about childhood illnesses among mothers of children less than four years of age and focus group discussions in 90 communities in each of the two states asked about household ownership of treated bed nets and their use for children under four years old. Bivariate and multivariate analyses examined associations between socio-economic and other variables and these outcomes in each state. RESULTS: Some 72% of 7,685 households in Cross River and 87% of 5,535 households in Bauchi State had at least one treated bed net. In Cross River, urban households were more likely to possess bed nets, as were less-poor households (enough food in the last week), those with a male head, and those from communities with a formal health facility. In Bauchi, less-poor households and those with a more educated head were more likely to possess nets. In households with nets, only about half of children under four years old always slept under a net: 54% of 11,267 in Cross River and 57% of 11,277 in Bauchi. Factors associated with use of nets for young children in Cross River were less-poor households, fewer young children in the household, more education of the father, antenatal care of the mother, and younger age of the child, while in Bauchi the factors were a mother with more education and antenatal care, and younger age of the child. Some focus groups complained of distribution difficulties, and many described misconceptions about adverse effects of nets as an important reason for not using them. CONCLUSION: Despite a recent campaign to distribute treated bed nets, disadvantaged households were less likely to possess them and to use them for young children. Efforts are needed to reach these households and to dispel fears about dangers of using treated nets. PMID- 25124832 TI - Is the incidence of temporomandibular disorder increased in polycystic ovary syndrome? AB - The prevalence of temporomandibular disorders is higher among women than men (ratio 3:1 -9:1). Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in women, which is characterised by chronic low-grade inflammation and excess of androgenic hormones that lead to metabolic aberrations and ovarian dysfunction. Increased activities of various matrix metalloproteinases (particularly MMP-2 and 9) in the serum of these patients has been reported, and it has been hypothesised that high activities of MMP may contribute to loss of matrix and chronic inflammation of the fibrocartilage in temporomandibular disorders. Our aim was to evaluate the incidence of temopormandibular dysfunction in women with PCOS compared with an age-matched, disease-free, control group. We studied 50 patients with previously diagnosed PCOS and 50 volunteers who had normal menstrual cycles. We made a comprehensive clinical examination of the temporomandibular joint (TMJ) and muscles of mastication in both groups and recorded the Visual Analogue Scores (VAS) for pain. There were significant differences (p<0.001) in the incidence of temporomandibular disorders (n=43 (86%) in the PCOS group compared with n=12 24% in the control group), muscle tenderness(n=32 (64%) in the PCOS group compared with n=14 (28%) in the control group) and pain in the TMJ (mean (SD) VAS 2.9 (2.61) compared with 0.3 (1.56). We confirm the higher incidence and severity of disorders of the TMJ in patients with PCOS and suspect that chronic low-grade inflammation may play a part in the aetiology of the disease. PMID- 25124833 TI - Attitudes towards pressure ulcer prevention: a psychometric evaluation of the Swedish version of the APuP instrument. AB - The primary aim was to conduct a psychometric evaluation of the Attitude towards Pressure ulcer Prevention (APuP) instrument in a Swedish context. A further aim was to describe and compare attitudes towards pressure ulcer prevention between registered nurses (RNs), assistant nurses (ANs) and student nurses (SNs). In total, 415 RNs, ANs and SNs responded to the questionnaire. In addition to descriptive and comparative statistics, confirmatory factor analyses were performed. Because of a lack of support for the instrument structure, further explorative and consecutive confirmatory tests were conducted. Overall, positive attitudes towards pressure ulcer prevention were identified for all three groups, but SNs reported lower attitude scores on three items and a higher score on one item compared to RNs and ANs. The findings indicated no support in this Swedish sample for the previously reported five-factor model of APuP. Further explorative and confirmative factor analyses indicated that a four-factor model was most interpretable: (i) Priority (five items), (ii) Competence (three items), (iii) Importance (three items) and (iv) Responsibility (two items). The five-factor solution could not be confirmed. Further research is recommended to develop a valid and reliable tool to assess nurses' attitudes towards pressure ulcer prevention working across different settings on an international level. PMID- 25124834 TI - Membrane protein resistance of oligo(ethylene oxide) self-assembled monolayers. AB - As part of an effort to develop biointerfaces for structure-function studies of integral membrane proteins (IMPs) a series of oligo(ethylene oxide) self assembled monolayers (OEO-SAMs) were evaluated for their resistance to protein adsorption (RPA) of IMPs on Au and Pt. Spectroscopic ellipsometry (SE) was used to determine SAM thicknesses and compare the RPA of HS(CH2)3O(CH2CH2O)6CH3 (1), HS(CH2)3O(CH2CH2O)6H (2), [HS(CH2)3]2CHO(CH2CH2O)6CH3 (3) and [HS(CH2)3]2CHO(CH2CH2O)6H (4), assembled from water. For both substrates, SAM thicknesses for 1 to 4 were found to be comparable indicating SAMs with similar surface coverages and OEO chain order and packing densities. Fibrinogen (Fb), a soluble plasma protein, and rhodopsin (Rd), an integral membrane G-protein coupled receptor, adsorbed to the SAMs of 1, as expected from previous reports, but not to the hydroxy-terminated SAMs of 2 and 4. The methoxy-terminated SAMs of 3 were resistant to Fb but, surprisingly, not to Rd. The stark difference between the adsorption of Rd to the SAMs of 3 and 4 clearly indicate that a hydroxy terminus of the OEO chain is essential for high RPA of IMPs. The similar thicknesses and high RPA of the SAMs of 2 and 4 show the conditions of protein resistance (screening the underlying substrate, packing densities, SAM order, and conformational mobility of the OEO chains) defined from previous studies on Au are applicable to Pt. In addition, the SAMs of 4, exhibiting the highest resistance to Fb and Rd, were placed in contact with undiluted fetal bovine serum for 2h. Low protein adsorption (~12.4ng/cm(2)), obtained under these more challenging conditions, denote a high potential of the SAMs of 4 for various applications requiring the suppression of non-specific protein adsorption. PMID- 25124835 TI - Promising dissolution enhancement effect of soluplus on crystallized celecoxib obtained through antisolvent precipitation and high pressure homogenization techniques. AB - Poor solubility and dissolution of hydrophobic drugs have become a major challenge in pharmaceutical development. Drug nanoparticles have been widely accepted to overcome this problem. The aim of this study was to manufacture celecoxib nanoparticles using antisolvent precipitation and high pressure homogenization techniques in the presence of varying concentrations of soluplus((r)) as a hydrophilic stabilizer. Antisolvent crystallization followed by freeze drying (CRS-FD) and antisolvent crystallization followed by high pressure homogenization and freeze drying (HPH-FD) were used to obtain celecoxib nanoparticles. The obtained nanoparticles were analyzed in terms of particle size, saturation solubility, morphology (optical and scanning electron microscopy), solid state (DSC, XRPD and FT-IR) and dissolution behavior. The results showed that celecoxib nanoparticle can be obtained when soluplus was added to the crystallization medium. In addition, the results showed that the concentration of soluplus and the method used to prepare nanoparticles can control the size and dissolution of celecoxib. Samples obtained in the presence of 5% soluplus through HPH technique showed an excellent dissolution (90%) within 4min. It is interesting to note that celecoxib samples with high crystallinity showed better dissolution than those celecoxib samples with high amorphous content, although they had the same concentration of soluplus. DSC and XRPD proved that samples obtained via HPH technique are more crystalline than the samples obtained through only antisolvent crystallization technique. PMID- 25124836 TI - Effect of exopolysaccharides on photocatalytic activity of ZnO nanoparticles. AB - Zinc oxide nanoparticles (ZnO NPs) are largely used in consumer products and industrial applications. The increased use of such materials may lead to its release into the environment. The study used chemically synthesized ZnO NPs and characterized by using UV-visible spectrophotometer, scanning electron microscopy, particle size analyzer and X-ray diffraction (XRD) analysis. The mean diameter of the particles was found to be 55+/-1.2nm. The XRD patterns exhibited hexagonal structure for ZnO NPs. The photocatalytic property of ZnO NPs was evaluated based on the UV-vis spectra changes of the methylene blue solution as a function of reaction time in the presence of ZnO NPs under visible light. The study suggests that ZnO NPs can be used as an efficient photocatalyst and the environmental factor such as exopolysaccharides could mask the photocatalytic activity of NPs. PMID- 25124837 TI - Evaluation of esophagogastric junction relaxation by 4-second Integrated Relaxation Pressure in achalasia using High Resolution Manometry with water perfused catheters. AB - BACKGROUND: Relaxation of the esophagogastric junction (EGJ) is now evaluated calculating 4-second integrated relaxation pressure (4-s IRP) by high resolution manometry (HREPT). Solid-state catheters have been used to define abnormal values. Our aim was to evaluate 4-s IRP in esophageal achalasia using HREPT with perfused catheters. METHODS: From June 2009 to June 2013, 936 HREPT studies have been performed in our unit. Of these, 194 patients having treated achalasia were excluded. Control group was constituted by 695 patients without achalasia, and 47 patients with untreated achalasia constituted the study group. HREPT was performed with water-perfused catheters. To establish the cut-off value for 4-s IRP that better discriminate patients with achalasia from all other patients, a receiver operating characteristic (ROC) analysis was performed. KEY RESULTS: Twenty three of 47 achalasia patients (49%) showed a 4-s IRP under 15 mmHg; and seven (15%) had a value under modified Chicago criteria. A cut-off value for 4-s IRP of 6.5 mmHg, calculated by ROC analysis, highly discriminates achalasia from the rest of the patients and especially from scleroderma patients (area under the curve: 0.997, 95% CI: 0.995-1.000; p < 0.001). CONCLUSIONS & INFERENCES: Cut-off values for 4-s IRP defined using HREPT with solid-state catheters are not adequate for diagnosing esophageal achalasia with water-perfused systems. A lower value, i.e., 6.5 mmHg, is suggested for this equipment. The diagnostic criteria of esophageal achalasia should be modified for HREPT performed with water perfused systems. PMID- 25124838 TI - Charles W. Vaughan, MD, 1926-2014. PMID- 25124839 TI - Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis. AB - OBJECTIVE: Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. METHODS: A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid IL2Rgamma(null) (NSG) mouse. RESULTS: The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. CONCLUSION: We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis. PMID- 25124840 TI - Longitudinal voice outcomes following laryngeal reinnervation via vagus-to recurrent laryngeal nerve anastomosis after vagal nerve sacrifice: a case series. AB - OBJECTIVE: This study aimed to describe longitudinal voice outcomes of vagus-to recurrent laryngeal nerve anastomosis following operative vagal nerve sacrifice. METHODS: Two patients who underwent anastomosis were assessed by a multidisciplinary voice team at 1, 4, 9, 12, and 18 months after vagal sacrifice. RESULTS: Long-term changes in voice function based on auditory perceptual measures of voice quality and visual perceptual changes in glottal closure were observed and maintained for 18 months after vagus-to-recurrent laryngeal nerve anastomosis in 2 patients with proximal vagal nerve sacrifice. Patients achieved acceptable voice outcomes and elected not to undergo further treatment, which was supported by Voice Handicap Index scores. CONCLUSION: Gradual restoration of voice following operative vagal sacrifice can be achieved over an 18-month period using vagus-to-recurrent laryngeal nerve anastomosis and warrants further investigation in appropriately selected patients. PMID- 25124841 TI - Facial palsy in Melkersson-Rosenthal syndrome and Bell's palsy: familial history and recurrence tendency. AB - OBJECTIVE: The aim of this study was to compare genetic predilection and recurrence tendency between facial palsy in Melkersson-Rosenthal syndrome (MRS) and Bell's palsy METHODS: We carried out an investigation on patients with facial palsy in MRS and those with Bell's palsy who visited the outpatient department in our hospital between February 2009 and February 2013. They were asked about familial history and whether it was the first episode, with the results recorded and compared. RESULTS: There were 16 patients with facial palsy in MRS and 860 patients with Bell's palsy involved in the study. Familial history was positive in 5 of 16 patients (31.3%) with facial palsy in MRS and 56 of 860 patients (6.5%) with Bell's palsy (P < .01). Twelve of 16 cases (75%) with facial palsy in MRS and 88 of 860 cases (10.2%) with Bell's palsy had a history of facial palsy in the past (P < .01). CONCLUSION: Compared to Bell's palsy, facial palsy in MRS has an obvious genetic predilection and recurrence tendency. PMID- 25124842 TI - Fluxionally chiral DMAP catalysts: kinetic resolution of axially chiral biaryl compounds. AB - Can organocatalysts that incorporate fluxional groups provide enhanced selectivity in asymmetric transformations? To address this issue, we have designed chiral 4-dimethylaminopyridine (DMAP) catalysts with fluxional chirality. These catalysts were found to be efficient in promoting the acylative kinetic resolution of secondary alcohols and axially chiral biaryl compounds with selectivity factors of up to 37 and 51, respectively. PMID- 25124844 TI - Evaluating degradation of silk's fibroin by attenuated total reflectance infrared spectroscopy: case study of ancient banners from Polish collections. AB - In this study a part of research where artificially aged model samples were used as a guideline to the mechanism of degradation is presented. In previous work Bombyx Mori silk samples were exposed to various environments such as different oxygen, water vapour and volatile organic products content, all at the temperature of 150 degrees C [11]. Based on those results gathered with by Attenuated Total Reflectance/Fourier Transform Infrared Spectroscopy (ATR-FTIR) the degradation estimators were proposed and classified as follows: (1) Primary functional groups estimators EAmideI/II - intensity ratios of Amide I C=O stretching vibration to Amide II N-H in-plane bending and C-N stretching vibrations A1620/A1514. ECOOH - band 1318 cm(-1) integral to band integral of CH3 bending vibration band located at 1442 cm(-1)P1318/P1442. (2) Secondary conformational estimators EcC=O2 - intensity ratios within Amide I C=O stretching vibration of parallel beta-sheet to antiparallel beta-sheet A1620/A1699. In this work estimators were verified against estimators calculated from spectra of silk samples from 8 museum objects: 3 from 19th, 2 from 18th, 1 from 17th and 2 from 16th century including 3 banners from the storage resources of the Wawel Royal Castle in Cracow, Poland. PMID- 25124843 TI - Expression quantitative trait loci infer the regulation of isoflavone accumulation in soybean (Glycine max L. Merr.) seed. AB - BACKGROUND: Mapping expression quantitative trait loci (eQTL) of targeted genes represents a powerful and widely adopted approach to identify putative regulatory variants. Linking regulation differences to specific genes might assist in the identification of networks and interactions. The objective of this study is to identify eQTL underlying expression of four gene families encoding isoflavone synthetic enzymes involved in the phenylpropanoid pathway, which are phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), chalcone synthase (CHS; EC 2.3.1.74), 2-hydroxyisoflavanone synthase (IFS; EC1.14.13.136) and flavanone 3 hydroxylase (F3H; EC 1.14.11.9). A population of 130 recombinant inbred lines (F5:11), derived from a cross between soybean cultivar 'Zhongdou 27' (high isoflavone) and 'Jiunong 20' (low isoflavone), and a total of 194 simple sequence repeat (SSR) markers were used in this study. Overlapped loci of eQTLs and phenotypic QTLs (pQTLs) were analyzed to identify the potential candidate genes underlying the accumulation of isoflavone in soybean seed. RESULTS: Thirty three eQTLs (thirteen cis-eQTLs and twenty trans-eQTLs) underlying the transcript abundance of the four gene families were identified on fifteen chromosomes. The eQTLs between Satt278-Sat_134, Sat_134-Sct_010 and Satt149-Sat_234 underlie the expression of both IFS and CHS genes. Five eQTL intervals were overlapped with pQTLs. A total of eleven candidate genes within the overlapped eQTL and pQTL were identified. CONCLUSIONS: These results will be useful for the development of marker-assisted selection to breed soybean cultivars with high or low isoflavone contents and for map-based cloning of new isoflavone related genes. PMID- 25124845 TI - Synthesis, characterization and biological activity of 2-acetylpyridine-alpha naphthoxyacetylhydrazone and its metal complexes [corrected]. AB - A new series of complexes of Ni(II), Co(II), Cu(II), Cd(II), Mn(II), Hg(II) and UO2(2+) derived from 2-acetylpyridine-alpha-naphthoxyacetylhydrazone (HA2PNA) have been prepared and characterized by elemental analyses, spectral (IR, UV visible, ESR and (1)H NMR) as well as magnetic and thermal measurements. The data revealed that the ligand acts as neutral NO, NN and NNO or mono-negative NNO chelate. On the basis of electronic spectral and magnetic moment data, an octahedral geometry is suggested for Mn(II), Co(II), Ni(II) and UO2(2+) complexes and a square planar arrangement for Cu(II) complex. The bond length, bond angle, HOMO, LUMO, dipole moment and charges on the atoms have been calculated to confirm the geometry of the ligand and the investigated complexes. The kinetic parameters were determined for thermal degradation stages of some complexes using Coats-Redfern and Horowitz-Metzger methods. Also, the ligand and its complexes were screened against antibacterial, antioxidant using DPPH radical and antitumor activities using in vitro Ehrlich ascites assay. PMID- 25124846 TI - Synthesis, structural and vibrational investigation on 2-phenyl-N-(pyrazin-2 yl)acetamide combining XRD diffraction, FT-IR and NMR spectroscopies with DFT calculations. AB - The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 2-phenyl-N-(pyrazin-2-yl)acetamide have been investigated experimentally and theoretically using Gaussian09 software package. The title compound was optimized by using the HF/6-31G(6D,7F) and B3LYP/6 31G(6D,7F) calculations. The geometrical parameters are in agreement with the XRD data. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. Gauge-including atomic orbital (1)H-NMR chemical shifts calculations were carried out and compared with experimental data. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. Molecular electrostatic potential was performed by the DFT method. First hyperpolarizability is calculated in order to find its role in non linear optics. From the XRD data, in the crystal, molecules are held together by strong C-H?O and N-H?O intermolecular interactions. PMID- 25124847 TI - Spectroscopic properties and the catalytic activity of new organo-lead supramolecular coordination polymer containing quinoxaline. AB - The 3D-supramolecular coordination polymer (SCP) (3)infinity[ Cu2(CN)3(Me3Pb)(qox)], 1, as the first example of the CuCN SCP containing the (Me3Pb) fragment, was explored to investigate its catalytic and photo-catalytic activities. The structure of 1 contains two chemically identical but crystallographically different [Cu2(CN)3?Me3Pb?qox]2 units with four Cu(I) sites assuming distorted TP-3 geometry. Two non-linear chains of equal abundance are formed producing corrugated parallel chains which are connected laterally by quinoxaline creating 2D-layers which are arranged parallel in an (AB?AB?AB)n fashion forming 3D-network. IR, mass, electronic absorption and fluorescence spectra are also investigated. The SCP 1 is diamagnetic and exhibits good catalytic and photo-catalytic activities for the degradation of methylene blue (MB). The reaction is first order with respect to MB dye. The irradiation of the reaction with UV-light enhanced the rate of MB mineralization. The efficiency of recycled the 1 and the mechanism of degradation of MB dye were investigated. PMID- 25124848 TI - SABRE is required for stabilization of root hair patterning in Arabidopsis thaliana. AB - Patterned differentiation of distinct cell types is essential for the development of multicellular organisms. The root epidermis of Arabidopsis thaliana is composed of alternating files of root hair and non-hair cells and represents a model system for studying the control of cell-fate acquisition. Epidermal cell fate is regulated by a network of genes that translate positional information from the underlying cortical cell layer into a specific pattern of differentiated cells. While much is known about the genes of this network, new players continue to be discovered. Here we show that the SABRE (SAB) gene, known to mediate microtubule organization, anisotropic cell growth and planar polarity, has an effect on root epidermal hair cell patterning. Loss of SAB function results in ectopic root hair formation and destabilizes the expression of cell fate and differentiation markers in the root epidermis, including expression of the WEREWOLF (WER) and GLABRA2 (GL2) genes. Double mutant analysis reveal that wer and caprice (cpc) mutants, defective in core components of the epidermal patterning pathway, genetically interact with sab. This suggests that SAB may act on epidermal patterning upstream of WER and CPC. Hence, we provide evidence for a role of SAB in root epidermal patterning by affecting cell-fate stabilization. Our work opens the door for future studies addressing SAB-dependent functions of the cytoskeleton during root epidermal patterning. PMID- 25124849 TI - Non-verbal communication in meetings of psychiatrists and patients with schizophrenia. AB - OBJECTIVE: Recent evidence found that patients with schizophrenia display non verbal behaviour designed to avoid social engagement during the opening moments of their meetings with psychiatrists. This study aimed to replicate, and build on, this finding, assessing the non-verbal behaviour of patients and psychiatrists during meetings, exploring changes over time and its association with patients' symptoms and the quality of the therapeutic relationship. METHOD: 40-videotaped routine out-patient consultations, involving patients with schizophrenia, were analysed. Non-verbal behaviour of patients and psychiatrists was assessed during three fixed, 2-min intervals using a modified Ethological Coding System for Interviews. Symptoms, satisfaction with communication and the quality of the therapeutic relationship were also measured. RESULTS: Over time, patients' non-verbal behaviour remained stable, whilst psychiatrists' flight behaviour decreased. Patients formed two groups based on their non-verbal profiles, one group (n = 25) displaying pro-social behaviour, inviting interaction and a second (n = 15) displaying flight behaviour, avoiding interaction. Psychiatrists interacting with pro-social patients displayed more pro-social behaviours (P < 0.001). Patients' pro-social profile was associated reduced symptom severity (P < 0.05), greater satisfaction with communication (P < 0.001) and positive therapeutic relationships (P < 0.05). CONCLUSION: Patients' non-verbal behaviour during routine psychiatric consultations remains unchanged, and is linked to both their psychiatrist's non-verbal behaviour and the quality of the therapeutic relationship. PMID- 25124850 TI - An improved and validated sample cleanup method for analysis of ethyl carbamate in Chinese liquor. AB - Ethyl carbamate (EC) is a potential human carcinogen widely existing in fermented foods and alcoholic beverages. The solid-phase extraction (SPE) coupled to gas chromatography mass spectrometry is a widely-used method to determine EC levels, but the accuracy varies with sample matrix and the effects of operation parameters are rarely examined. In this study, the influence factors involved in EC determination were investigated using Chinese liquor as sample matrix, and the improved method was further applied. Three types of SPE columns, including diatomite, Florisil, and primary-secondary amine, were compared in extraction efficiency, and the diatomite column exhibited the highest extraction efficiency. The optimal volumes of elution solvents with diatomite column were 15 mL for 3-mL samples solution loaded. In addition, the alcoholic strength for EC determination should be diluted below 20% (v/v) to avoid the enhancement of matrix-induced chromatographic response. Moreover, the pH neutralization could help improve EC recovery and peak resolution, reducing interfering effects. Based on these results, the improved method showed that the limit of detection, the limit of quantification, and average recoveries were 1.10 MUg/L, 3.65 MUg/L, and 93.06%, respectively. To further elucidate the underlying factors related to EC accumulation, partial least square regression analysis was conducted, and the results suggested that EC levels had the closest relationship with alcoholic strength among the remaining precursors. PMID- 25124852 TI - Neurite-J: an image-J plug-in for axonal growth analysis in organotypic cultures. AB - BACKGROUND: Previous studies in our lab proposed a method of dorsal root ganglia (DRG) and spinal cord slice (SC) organotypic 3D cultures to study motor and sensory axonal regeneration. Although these models are useful to test how different factors affect axonal growth, manual sample analysis can be inaccurate and time-consuming. Thus, we designed and set-up a plug-in to quantify axonal growth in 3D organotypic cultures. NEW METHOD: DRG and SC were cultured in a 3D collagen matrix. Explants were maintained in culture medium (control condition) or in culture medium supplemented with neurotrophins. Neurites were immunolabeled against RT-97 and pictures were obtained using an epifluorescence microscope. To quantify axonal growth we adapted the Sholl method of concentric rings to our cultures and the algorithm was implemented as an ImageJ plug-in. COMPARISON WITH EXISTING METHOD(S): Our method and plug-in was compared with standard Sholl method demonstrating better accuracy. In comparison with Neurite-J, manual measures of axonal growth in organotypic cultures require more time and provide fewer data than our proposed method. RESULTS: Neurite-J gives a reliable quantitative analysis of neurite growth, providing counts of neurite number and neurite area at different distances from the explant. Moreover, this plug-in follows lineal and semi-logarithmic analysis of the Sholl method, yielding a numerical value of neurite outgrowth useful for comparing different experimental conditions. CONCLUSION: Neurite-J provides a quantification method of neurite arbors in 3D organotypic cultures that gives the researcher an easy, fast and reliable tool to study axonal growth. PMID- 25124851 TI - Skull-stripping with machine learning deformable organisms. AB - BACKGROUND: Segmentation methods for medical images may not generalize well to new data sets or new tasks, hampering their utility. We attempt to remedy these issues using deformable organisms to create an easily customizable segmentation plan. We validate our framework by creating a plan to locate the brain in 3D magnetic resonance images of the head (skull-stripping). NEW METHOD: Our method borrows ideas from artificial life to govern a set of deformable models. We use control processes such as sensing, proactive planning, reactive behavior, and knowledge representation to segment an image. The image may have landmarks and features specific to that dataset; these may be easily incorporated into the plan. In addition, we use a machine learning method to make our segmentation more accurate. RESULTS: Our method had the least Hausdorff distance error, but included slightly less brain voxels (false negatives). It also had the lowest false positive error and performed on par to skull-stripping specific method on other metrics. COMPARISON WITH EXISTING METHOD(S): We tested our method on 838 T1 weighted images, evaluating results using distance and overlap error metrics based on expert gold standard segmentations. We evaluated the results before and after the learning step to quantify its benefit; we also compare our results to three other widely used methods: BSE, BET, and the Hybrid Watershed algorithm. CONCLUSIONS: Our framework captures diverse categories of information needed for brain segmentation and will provide a foundation for tackling a wealth of segmentation problems. PMID- 25124855 TI - Sexual precocity of Nellore bulls that are offspring of super precocious, precocious and normal cows in extensive farming conditions. AB - The objective of this work was to verify that mothers classified as super precocious (M1) and precocious (M2) produce more precocious bulls than females classified as normal (M3). This study included 21,186 animals with an average age of 21.29 +/- 1.77 months that underwent a breeding soundness evaluation from 1999 to 2008. Of these animals, 2019, 6059 and 13,108 were offspring of M1, M2 and M3 females, respectively. In the breeding soundness examination, the animals were classified as sound for reproduction, sound under a natural mating regime, unsound for reproduction and discarded. To compare the averages obtained for each category of mother within the individual breeding soundness classes, a chi-square test with a 5% error probability was used, considering the effects of year and month of birth and farm. For the three classes of mothers (M1, M2 and M3), 67.26, 67.22 and 64.16% of bull calves were considered sound for reproduction and 19.71, 19.46 and 21.90% were considered unsound for reproduction, respectively. There was no difference in the frequency of animals that were sound for reproduction under the natural breeding regime between the three classes of mothers (8.87, 9.31 and 9.19%, respectively). There was a difference between the numbers of precocious and normal females that were discarded, with frequencies of 4.01 and 4.75%, respectively (p < 0.05). There were differences in year and month of birth and farm between super precocious and precocious cows in relation to the breeding soundness classification of the animals. It was concluded that the bull offspring of super precocious and precocious cows presented a higher percentage of approval in the breeding soundness examination than the bull offspring of normal cows, demonstrating that the selection for precocity of females has contributed to an increase in the sexual precocity of the herd in relation to the sexual maturity of bulls. PMID- 25124853 TI - Long noncoding RNA associated-competing endogenous RNAs in gastric cancer. AB - Some long noncoding RNAs (lncRNAs) play important roles in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the roles of lncRNA associated-ceRNAs in oncogenesis are not fully understood. Here, based on lncRNA microarray data of gastric cancer, bioinformatic algorithm miRcode and microRNA (miRNA) targets database TarBase, we first constructed an lncRNA-miRNA mRNA network. Then, we confirmed it by data of six types of other cancer including head and neck squamous cell carcinoma, prostate cancer, papillary thyroid carcinoma, pituitary gonadotrope tumors, ovarian cancer, and chronic lymphocytic leukemia. The results showed a clear cancer-associated ceRNA network. Eight lncRNAs (AC009499.1, GACAT1, GACAT3, H19, LINC00152, AP000288.2, FER1L4, and RP4-620F22.3) and nine miRNAs (miR-18a-5p, miR-18b-5p, miR-19a-3p, miR-20b 5p, miR-106a-5p, miR-106b-5p, miR-31-5p, miR-139-5p, and miR-195-5p) were involved. For instance, through its miRNA response elements (MREs) to compete for miR-106a-5p, lncRNA-FER1L4 regulates the expression of PTEN, RB1, RUNX1, VEGFA, CDKN1A, E2F1, HIPK3, IL-10, and PAK7. Furthermore, cellular experimental results indicated that FER1L4-small interfering RNA (siRNA) simultaneously suppressed FER1L4 and RB1 mRNA level. These results suggest that lncRNAs harbor MREs and play important roles in post-transcriptional regulation in cancer. PMID- 25124854 TI - Association of gene variants of the renin-angiotensin system with accelerated hippocampal volume loss and cognitive decline in old age. AB - OBJECTIVE: Genetic factors confer risk for neuropsychiatric phenotypes, but the polygenic etiology of these phenotypes makes identification of genetic culprits challenging. An approach to this challenge is to examine the effects of genetic variation on relevant endophenotypes, such as hippocampal volume loss. A smaller hippocampus is associated with gene variants of the renin-angiotensin system (RAS), a system implicated in vascular disease. However, no studies to date have investigated longitudinally the effects of genetic variation of RAS on the hippocampus. METHOD: The authors examined the effects of polymorphisms of AGTR1, the gene encoding angiotensin-II type 1 receptor of RAS, on longitudinal hippocampal volumes of older adults. In all, 138 older adults (age >=60 years) were followed for an average of about 4 years. The participants underwent repeated structural MRI and comprehensive neurocognitive testing, and they were genotyped for four AGTR1 single-nucleotide polymorphisms (SNPs) with low pairwise linkage disequilibrium values and apolipoprotein E (APOE) genotype. RESULTS: Genetic variants at three AGTR1 SNPs (rs2638363, rs1492103, and rs2675511) were independently associated with accelerated hippocampal volume loss over the 4-year follow-up period in the right but not left hemisphere. Intriguingly, these AGTR1 risk alleles also predicted worse episodic memory performance but were not related to other cognitive measures. Two risk variants (rs2638363 and rs12721331) interacted with the APOE4 allele to accelerate right hippocampal volume loss. CONCLUSIONS: Risk genetic variants of the RAS may accelerate memory decline in older adults, an effect that may be conferred by accelerated hippocampal volume loss. Molecules involved in this system may hold promise as early therapeutic targets for late-life neuropsychiatric disorders. PMID- 25124856 TI - Helminths in feline coprolites up to 9000 years in the Brazilian Northeast. AB - The identification of parasites in animal coprolites has been an important tool to promote knowledge about parasites infecting different zoological groups in the past. It also helps the understanding of parasites causing zoonoses, which is especially important for animals that were part of the diet of prehistoric human groups. Nevertheless, the study of feline coprolites is still scarce. This study analyzed 30 feline coprolites from southeastern Piaui taken from archeological sites used by human groups in the past. Eggs of Spirometra sp., Toxocara cati, Spirurida, Oxyuroidea Calodium cf. hepaticum, Trichuris cf. muris, Trichuris sp., and other Trichuridae, Oncicola sp., and nematode larvae were found. Some of these findings reflect the consumption of infected prey. The role of felines in the transmission of helminthes causing zoonoses in the region is discussed. PMID- 25124857 TI - The antimicrobial and antibiofilm activities of copper(II) complexes. AB - Biofilm-related bacterial infections pose a significant problem, as they are generally more tolerant to antibiotics and the immune system. Development of novel compounds with antibiofilm activity is therefore paramount. In this study we have analysed metal complexes of the general structure [M(IL)(AL)](2+) (where IL represents functionalised 1,10-phenanthrolines and AL represents 1S,2S- or 1R,2R-diaminocyclohexane) and [Cu(IL)3](2+). Antimicrobial activity was tested on a number of bacterial strains, showing that copper(II) compounds were active against both Gram-positive and Gram-negative bacteria, albeit that activity was generally higher for the former. The antibiofilm activity was then determined against a clinical isolate of meticillin-resistant Staphylococcus aureus (MRSA). Strikingly, the copper complexes tested showed significant activity against biofilms, and were better in the removal of biofilms than vancomycin, an antibiotic that is currently used in the treatment of MRSA infections. PMID- 25124858 TI - Electrospun P34HB fibres: a scaffold for tissue engineering. AB - OBJECTIVES: Amongst the fourth generation of PHAs is bio-plasticpoly3 hydroxybutyrate4-hydroxybutyrate (P34HB); it is thus appropriate to perform novel research on its uses and applications. The main objective of this study was to determine whether electrospun P34HB fibres would accommodate viability, growth and differentiation of mouse adipose-derived stem cells (mASCs). MATERIALS AND METHODS: In the present study, we looked at P34HB in two forms, electrospun P34HB fibres and P34HB film. Morphology of electrospun P34HB fibres and P34HB film were characterized using scanning electron microscopy, fluorescence microscopy and confocal laser scanning microscopy, after cell seeding. Cell adhesion, proliferation and cytotoxicity tests were conducted on both by MTT and CCK-8 assays, respectively. After being cultured with osteogenic induction, expression of adipogenic genes Runx2, OPN and OCN, were examined by real-time PCR. RESULTS: By scanning electron microscopy, light microscopy and confocal laser scanning microscopy, we observed that the mASCs grew well associated with the P34HB materials. After MTT and CCK-8 assay, we concluded that P34HB would, indeed, be a material suitable for further cell adhesion and proliferation studies. More importantly, we found that the P34HB matrices promoted expression of Runx2, OPN and OCN with osteogenic induction. CONCLUSIONS: In this investigation, we can confirm that the electrospun P34HB fibres accommodated survival, proliferation and differentiation of mASCs, and we have been able to draw the conclusion that fibre scaffolds produced by the electrospinning process are promising for application of bone tissue engineering. PMID- 25124860 TI - Interaction Between Words and Symbolic Gestures as Revealed By N400. AB - What happens if you see a person pronouncing the word "go" after having gestured "stop"? Differently from iconic gestures, that must necessarily be accompanied by verbal language in order to be unambiguously understood, symbolic gestures are so conventionalized that they can be effortlessly understood in the absence of speech. Previous studies proposed that gesture and speech belong to a unique communication system. From an electrophysiological perspective the N400 modulation was considered the main variable indexing the interplay between two stimuli. However, while many studies tested this effect between iconic gestures and speech, little is known about the capability of an emblem to modulate the neural response to subsequently presented words. Using high-density EEG, the present study aimed at evaluating the presence of an N400 effect and its spatiotemporal dynamics, in terms of cortical activations, when emblems primed the observation of words. Participants were presented with symbolic gestures followed by a semantically congruent or incongruent verb. A N400 modulation was detected, showing larger negativity when gesture and words were incongruent. The source localization during N400 time window evidenced the activation of different portions of temporal cortex according to the gesture and word congruence. Our data provide further evidence of how the observation of an emblem influences verbal language perception, and of how this interplay is mainly instanced by different portions of the temporal cortex. PMID- 25124861 TI - Stereoselective synthesis of lanthionine derivatives in aqueous solution and their incorporation into the peptidoglycan of Escherichia coli. AB - The three diastereoisomers-(R,R), (S,S) and meso-of lanthionine were synthesized in aqueous solution with high diastereoselectivity (>99%). The (S) and (R) enantiomers of two differently protected sulfamidates were opened by nucleophilic attack of (R) or (S)-cysteine. Acidification and controlled heating liberated the free lanthionines. Using the same chemistry, an alpha-benzyl lanthionine was also prepared. The proposed method, which avoids the need of enrichment by recrystallization, opens the way to the labelling of these compounds with (35)S. Furthermore, in vivo bioincorporation into Escherichia coli W7 was studied. No incorporation of alpha-benzyl lanthionine was observed. In contrast, meso lanthionine can effectively replace meso-diaminopimelic acid in vivo, while in the presence of (R,R)-lanthionine the initial increase of bacterial growth was followed by cell lysis. In the future, meso-[(35)S]lanthionine could be used to study the biosynthesis of peptidoglycan and its turnover in relation to cell growth and division. PMID- 25124859 TI - Plasticity versus specificity in RTK signalling modalities for distinct biological outcomes in motor neurons. AB - BACKGROUND: Multiple growth factors are known to control several aspects of neuronal biology, consecutively acting as morphogens to diversify neuronal fates, as guidance cues for axonal growth, and as modulators of survival or death to regulate neuronal numbers. The multiplicity of neuronal types is permitted by the combinatorial usage of growth factor receptors, each of which is expressed in distinct and overlapping subsets of neurons, and by the multitasking role of growth factor receptors, which recruit multiple signalling cascades differentially required for distinct biological outcomes. We have explored signalling robustness in cells where a given receptor tyrosine kinase (RTK) elicits qualitatively distinct outcomes. As the HGF/Met system regulates several biological responses in motor neurons (MN) during neuromuscular development, we have investigated the signalling modalities through which the HGF/Met system impacts on MN biology, and the degree of robustness of each of these functions, when challenged with substitutions of signalling pathways. RESULTS: Using a set of mouse lines carrying signalling mutations that change the Met phosphotyrosine binding preferences, we have asked whether distinct functions of Met in several MN subtypes require specific signalling pathways, and to which extent signalling plasticity allows a pleiotropic system to exert distinct developmental outcomes. The differential ability of signalling mutants to promote muscle migration versus axonal growth allowed us to uncouple an indirect effect of HGF/Met signalling on nerve growth through the regulation of muscle size from a direct regulation of motor growth via the PI3 kinase (PI3K), but not Src kinase, pathway. Furthermore, we found that HGF/Met-triggered expansion of Pea3 expression domain in the spinal cord can be accomplished through several alternative signalling cascades, differentially sensitive to the Pea3 dosage. Finally, we show that the regulation of MN survival by HGF/Met can equally be achieved in vitro and in vivo by alternative signalling cascades involving either PI3K-Akt or Src and Mek pathways. CONCLUSIONS: Our findings distinguish MN survival and fate specification, as RTK-triggered responses allowing substitutions of the downstream signalling routes, from nerve growth patterning, which depends on a selective, non-substitutable pathway. PMID- 25124863 TI - Reliability and validity testing of automated scoring in obstructive sleep apnea diagnosis with the Embletta X100. AB - OBJECTIVES/HYPOTHESIS: To verify the reliability and validity of automated scoring and compare it to that of manual scoring for diagnosing obstructive sleep apnea using an Embletta X100 level 2 portable device. STUDY DESIGN: Retrospective study. METHODS: A total of 116 patients with suspected obstructive sleep apnea who had successfully received portable polysomnography with the Embletta X100 were examined. All polysomnography data were analyzed by automated and manual methods. Manual scoring was performed according to the revised American Academy of Sleep Medicine 2012 criteria. Automated scoring was analyzed using the automatic algorithm, which was updated with the American Academy of Sleep Medicine 2012 criteria. All parameters were evaluated statistically using correlation analysis and paired t tests. RESULTS: The apnea-hypopnea index for automated scoring and manual scoring with the Embletta X100 were moderately correlated (r = 0.76, P < .001). However, there was poor agreement (Bland-Altman plot, kappa = 0.34, 0.33, and 0.26; cutoff value = 5, 15, and 30), and the apnea hypopnea index data were generally excessively underestimated based on diagnostic agreement and disagreement criteria. Furthermore, the apnea-hypopnea index severity (Kendall tau-b = 0.62) between automated and manual scoring lacked good concordance. CONCLUSIONS: Automated scoring using the Embletta X100 was statistically moderately related to the manual scoring results. However, automated scoring tended to excessively underestimate the apnea-hypopnea index data compared to manual scoring. Thus, manual scoring by a sleep expert is essential for obstructive sleep apnea diagnosis with the Embletta X100. LEVEL OF EVIDENCE: 4. PMID- 25124864 TI - Get a Life? The Impact of the European Working Time Directive: The Case of UK Senior Doctors. AB - This paper seeks to identify the effect of the implementation of the European Working Time Directive on the working hours of UK doctors. The Labour Force Survey is used to compare the working hours of doctors with a variety of control groups before and after the implementation of the directive. The controls include those unconstrained by the directive and doctor counterparts working in Europe. We use differences-in-differences and matching methods to estimate the impact of this natural experiment, distinguishing between the anticipation and enactment of the European Working Time Directive. We find that the legislation reduced the hours of senior doctors by around 8 hours in total including the component attributable to anticipation effects and allowing for (exogenously set) rising wages. Copyright (c) 2014 John Wiley & Sons, Ltd. PMID- 25124862 TI - Ricinine: a pyridone alkaloid from Ricinus communis that activates the Wnt signaling pathway through casein kinase 1alpha. AB - Wnt signaling plays important roles in proliferation, differentiation, development of cells, and various diseases. Activity-guided fractionation of the MeOH extract of the Ricinus communis stem led to the isolation of four compounds (1-4). The TCF/beta-catenin transcription activities of 1 and 3 were 2.2 and 2.5 fold higher at 20 and 30MUM, respectively. Cells treated with ricinine (1) had higher beta-catenin and lower of p-beta-catenin (ser 33, 37, 45, Thr 41) protein levels, whereas glycogen synthase kinase 3beta (GSK3beta) and casein kinase 1alpha (CK1alpha) protein levels remained unchanged. Cells treated with pyrvinium, an activator of CK1alpha, had lower beta-catenin levels. However, the combined treatment of pyrvinium and 1 led to higher beta-catenin levels than those in cells treated with pyrvinium alone, which suggested that 1 inhibited CK1alpha activity. Furthermore, 1 increased beta-catenin protein levels in zebrafish embryos. These results indicated that 1 activated the Wnt signaling pathway by inhibiting CK1alpha. PMID- 25124865 TI - Ionic liquids as novel solvents for the synthesis of sugar fatty acid ester. AB - Sugar fatty acid esters are bio-surfactants known for their non-toxic, non-ionic, and high biodegradability . With great emulsifying and conditioning effects, sugar fatty acids are widely used in the food, pharmaceutical, and cosmetic industries. Biosynthesis of sugar fatty acid esters has attracted growing attention in recent decades. In this study, the enzymatic synthesis of sugar fatty acid esters in ionic liquids was developed, optimized, and scaled up. Reaction parameters affecting the conversion yield of lipase-catalyzed synthesis of glucose laurate from glucose and vinyl laurate (i.e. temperature, vinyl laurate/glucose molar ratio, and enzyme loads) were optimized by response surface methodology (RSM). In addition, production was scaled up to 2.5 L, and recycling of enzyme and ionic liquids was investigated. The results showed that under optimal reaction conditions (66.86 degrees C, vinyl laurate/glucose molar ratio of 7.63, enzyme load of 73.33 g/L), an experimental conversion yield of 96.4% was obtained which is close to the optimal value predicted by RSM (97.16%). A similar conversion yield was maintained when the reaction was carried out at 2.5 L. Moreover, the enzymes and ionic liquids could be recycled and reused effectively for up to 10 cycles. The results indicate the feasibility of ionic liquids as novel solvents for the biosynthesis of sugar fatty acid esters. PMID- 25124866 TI - Risk of ischemic stroke in primary aldosteronism patients. AB - BACKGROUND: High aldosterone concentrations are associated with the risk of stroke that is independent of blood pressure levels. We investigated the risk of ischemic stroke in primary aldosteronism (PA) patients. METHODS: This retrospective case-control study was based on the Taiwan Primary Aldosteronism Investigation (TAIPAI) database from 2004 to 2010. The study group comprised the patients who developed ischemic stroke after the diagnosis of PA. The PA patients who did not develop stroke were matched according to age and sex as the control group. A multivariate logistic regression model was performed to determine the risk factors of ischemic stroke. RESULTS: Of 339 patients diagnosed with PA, 22 patients (6.5%) developed de novo ischemic stroke. The PA patients with stroke suffered from a longer hypertensive period (11.0+/-6.5 vs 7.8+/-8.3, P=.007) and a higher prevalence of proteinuria than those who did not develop stroke (40.9% vs 12.9%, P=.002). A multivariate logistic regression model showed that PA patients with proteinuria (HR 3.58, P=.02), preexisting coronary artery disease (HR 11.12, P<.001) or left ventricular hypertrophy (HR 3.09, P=.047) were associated with an increased risk of ischemic stroke. CONCLUSIONS: Proteinuria, a medical history of coronary artery disease or left ventricular hypertrophy, was associated with an increased risk of ischemic stroke in PA patients. Our results suggest that a public health initiative is necessary to enhance the follow-up of proteinuria and to manage subsequent stroke among patients with aldosteronism. PMID- 25124867 TI - Effects of the ABCG2 and ABCB1 drug transporter polymorphisms on the pharmacokinetics of bicalutamide in humans. AB - BACKGROUNDS: Bicalutamide is an oral non-steroidal anti-androgen used in the treatment of prostate cancer. Drug transporters P-glycoprotein encoded by ABCB1 and breast cancer resistance protein (BCRP) encoded by ABCG2 are involved in the transportation of bicalutamide and its treatment failure. We evaluated the roles of ABCB1 and ABCG2 genetic polymorphisms in the pharmacokinetics of bicalutamide in humans. METHODS: After a single oral dose of 150mg bicalutamide was administered, plasma concentrations of bicalutamide were measured, and pharmacokinetic analyses were performed in 27 healthy subjects according to ABCB1 (c.1236C>T, c.2677G>T/A, and c.3435C>T) and ABCG2 (c.34G>A and c.421C>A). RESULTS: ABCB1 polymorphisms did not affect the plasma levels of bicalutamide and the pharmacokinetic parameters did not differ among ABCB1 genotype groups. However, the ABCG2 c.421C>A polymorphism significantly influenced the plasma levels and pharmacokinetics of bicalutamide gene dose-dependently. CONCLUSIONS: The ABCB1 genetic polymorphisms did not influence the pharmacokinetics of bicalutamide. However, ABCG2 c.421C>A significantly and gene dose-dependently influenced its pharmacokinetics, but c.34G>A did not. PMID- 25124868 TI - Effect of JEZTC, a synthetic compound, on proliferation and phenotype maintenance of rabbit articular chondrocytes in vitro. AB - Antioxidant may provide anti-arthritic effect that contributes to resolution of inflammation. Gallic acid (GA) and its derivatives were reported to be effective in treatment of arthritis. But GA-suppressed cell proliferation may compromise its effect on chondro-protection. In this study, we synthesized sulfonamido-based gallate-JEZTC and investigated its effect on rabbit articular chondrocytes through examination of the cell proliferation, morphology, viability, glycosaminoglycan (GAG) synthesis, and cartilage-specific gene expression. Results showed that JEZTC could effectively promote chondrocyte growth and enhance secretion and synthesis of cartilage extracellular matrix (ECM) by upregulating expression levels of aggrecan, collagen II, and Sox9 genes. Expression of collagen I which marked chondrocyte dedifferentiation was effectively downregulated by JEZTC. In addition, hypertrophy that may lead to chondrocyte ossification could not be detected in JEZTC groups. The results indicated JEZTC can well preserve the phenotype of chondrocytes. Range of 2.344 to 9.375 MUg/ml is the recommended dose of JEZTC, which showed increased cell proliferation. Especially, JEZTC of 4.688 MUg/ml showed the best performance. This study might provide a basis for development of a novel agent for the treatment of symptomatic chondral and osteochondral lesions. PMID- 25124869 TI - Recellularization potential assessment of Wharton's Jelly-derived endothelial progenitor cells using a human fetal vascular tissue model. AB - Mesenchymal stem cells isolated from Wharton's Jelly have demonstrated an excellent differentiation potential into the endothelial lineage. We hypothesize that endothelial progenitor cells differentiated from Wharton's Jelly-derived mesenchymal stem cells have the potential to repopulate a decellularized vascular bed employed as a biological scaffold. For this purpose, we aimed at investigating the behavior of the endothelial progenitor cells in the decellularized matrix and their potential to repopulate decellularized human vascular tissue. Our main objectives were to differentiate Wharton's Jelly derived mesenchymal stem cells into endothelial progenitor cells and to obtain a human vascular tissue slice experimental model using the umbilical cord arteries. We employed a decellularization method using enzymatic treatment of the umbilical cord arteries and a recellularization method with the endothelial progenitor cells differentiated from Wharton's Jelly mesenchymal cells in a co-culture system, in order to investigate our hypothesis. The cellular integration within the biological scaffold was determined by using flow cytometry analysis and confirmed by visualization of histological staining as well as fluorescence microscopy. The morphological observations of the recellularized scaffolds revealed the presence of endothelial progenitor cells within the decellularized tissue slices, displaying no degradation of the scaffold's extracellular matrix. The flow cytometry analysis revealed the presence of Wharton's Jelly-derived endothelial progenitor cells population in the decellularized fetal blood vessel scaffold after recellularization. In conclusion, our results have shown that an in vitro human vascular tissue slice experimental model using decellularized human fetal arteries is able to sustain an adequate scaffold for cellular implants. PMID- 25124871 TI - Improved efficiency of definitive endoderm induction from human induced pluripotent stem cells in feeder and serum-free culture system. AB - Improvement of methods to produce endoderm-derived cells from pluripotent stem cells is important to realize high-efficient induction of endodermal tissues such as pancreas and hepatocyte. Difficulties hampering such efforts include the low efficiency of definitive endoderm cell induction and establishing appropriate defined culture conditions to ensure a safe cell source for human transplantation. Based on previous studies, we revised the experimental condition of definitive endoderm induction in feeder- and serum-free culture. Our results suggested that CHIR99021 is more effective than Wnt3A ligand in feeder- and serum free conditions. In addition, keeping cell density low during endoderm induction is important for the efficiency. On the other hand, we showed that overtreatment with CHIR99021 converted the cells into BRACHYURY-expressing posterior mesoderm cells rather than endoderm, indicating strict CHIR99021 treatment requirements for endoderm differentiation. Nevertheless, these results should enable better control in the production of definitive endoderm-derived cells. PMID- 25124872 TI - Meiotic maturation of oocytes recovered from the ovaries of Indian big cats at postmortem. AB - In order to increase the available sources of genetic material for endangered members of the great cat family, this study was designed to assess the meiotic competence of oocytes recovered from postmortem ovaries of the Indian leopard, tiger and lion. The average number of oocytes that were recovered per ovary was 11.0 +/- 5.0, 11.0 +/- 3.5 and 21.3 +/- 8.8 for tiger, lion and leopard, respectively. The proportion of culture grade oocytes for tiger, lion and leopard were 72.7, 78.8 and 71.9%, respectively. The culture grade oocytes were matured in tissue culture medium 199 modified with sodium bicarbonate supplemented with 0.3% BSA (fatty acid-free) (w/v), 10 MUg/ml FSH, 6 IU/ml LH, 1 MUg/ml 17beta estradiol, 0.36 mM pyruvate, 2.2 mM calcium lactate, 2.0 mM L-glutamine, 100 IU/ml penicillin and 0.1 mg/ml streptomycin in an incubator with 5% CO2 under humidified air at 38.5 degrees C for 36 h. After in vitro maturation, 56.3, 53.8 and 58.7% of the tiger, lion and leopard oocytes, respectively, were matured. The proportion of oocytes that extruded first polar body was significantly higher when the oocytes were collected from the animals of less than 15 yr of age compared to above 15 yr. These findings suggest that the oocytes recovered from ovaries of tiger, lion and leopard immediately postmortem can be successfully matured to MII stage. PMID- 25124870 TI - Hyaluronan in aged collagen matrix increases prostate epithelial cell proliferation. AB - The extracellular matrix (ECM) of the prostate, which is comprised primarily of collagen, becomes increasingly disorganized with age, a property that may influence the development of hyperplasia and cancer. Collageous ECM extracted from the tails of aged mice exhibits many characteristics of collagen in aged tissues, including the prostate. When polymerized into a 3-dimensional (3D) gel, these collagen extracts can serve as models for the study of specific cell-ECM interactions. In the present study, we examined the behaviors of human prostatic epithelial cell lines representing normal prostate epithelial cells (PEC), benign prostatic hyperplasia (BPH-1), and adenocarcinoma (LNCaP) cultured in contact with 3D gels made from collagen extracts of young and aged mice. We found that proliferation of PEC, BPH-1, and LNCaP cells were all increased by culture on aged collagen gels relative to young collagen gels. In examining age-associated differences in the composition of the collagen extracts, we found that aged and young collagen had a similar amount of several collagen-associated ECM components, but aged collagen had a much greater content of the glycosaminoglycan hyaluronan (HA) than young collagen. The addition of HA (of similar size and concentration to that found in aged collagen extracts) to cells placed in young collagen elicited significantly increased proliferation in BPH-1 cells, but not in PEC or LNCaP cells, relative to controls not exposed to HA. Of note, histochemical analyses of human prostatic tissues showed significantly higher expression of HA in BPH and prostate cancer stroma relative to stroma of normal prostate. Collectively, these results suggest that changes in ECM involving increased levels of HA contribute to the growth of prostatic epithelium with aging. PMID- 25124873 TI - Repression of multiple CYP2D genes in mouse primary hepatocytes with a single siRNA construct. AB - The Cyp2d subfamily is the second most abun-dant subfamily of hepatic drug metabolizing CYPs. In mice, there are nine Cyp2d members that are believed to have redundant catalytic activity. We are testing and optimizing the ability of one short interfering RNA (siRNA) construct to knockdown the expression of multiple mouse Cyp2ds in primary hepatocytes. Expression of Cyp2d10, Cyp2d11, Cyp2d22, and Cyp2d26 was observed in the primary male mouse hepatocytes. Cyp2d9, which is male-specific and growth hormone-dependent, was not expressed in male primary hepatocytes, potentially because of its dependence on pulsatile growth hormone release from the anterior pituitary. Several different siRNAs at different concentrations and with different reagents were used to knockdown Cyp2d expression. siRNA constructs designed to repress only one construct often mildly repressed several Cyp2d isoforms. A construct designed to knockdown every Cyp2d isoform provided the best results, especially when incubated with transfection reagents designed specifically for primary cell culture. Interestingly, a construct designed to knockdown all Cyp2d isoforms, except Cyp2d10, caused a 2.5* increase in Cyp2d10 expression, presumably because of a compensatory response. However, while RNA expression is repressed 24 h after siRNA treatment, associated changes in Cyp2d-mediated metabolism are tenuous. Overall, this study provides data on the expression of murine Cyp2ds in primary cell lines, valuable information on designing siRNAs for silencing multiple murine CYPs, and potential pros and cons of using siRNA as a tool for repressing Cyp2d and estimating Cyp2d's role in murine xenobiotic metabolism. PMID- 25124874 TI - Electronic medical record adoption in Oklahoma practices: rural-urban differences and the role of broadband availability. AB - PURPOSE: Most recent research has not found significant differences in electronic medical record (EMR) adoption rates between rural and urban physicians. However, few studies have assessed rural/urban differences at a lower level--for instance, by specialty or size of practice. Determinants of EMR adoption by physician practices in Oklahoma are explored, including the potential role of broadband availability (which is required for EMR interoperability). METHODS: Surveys of 2,800 unique Oklahoma physician practices in 2011 were meshed with data from the National Broadband Map for that same year. Summary statistics from the survey data allowed for comparison of EMR adoption rates by sub category. Logistic regressions were used to tease out the impact of location, specialty, and broadband availability on the EMR adoption decision. FINDINGS: Similar overall EMR adoption rates in rural and urban practices masked significant differences among specific subcategories. In particular, solo practices in rural areas are much more likely to adopt EMRs than are their urban counterparts (41% vs 33%, P < .01); rural psychiatric practices also have measurably higher adoption rates (59% vs 25%, P < .01). Logistic regression results demonstrate that determinants of adoption do vary between rural and urban practices. No statistical relationship between EMR adoption and measures of broadband availability was found. CONCLUSIONS: Measurable differences in EMR adoption rates do exist between rural and urban practices for specific physician categories in Oklahoma. Targeted policies may be important for increasing EMR adoption, but policy efforts focusing solely on broadband availability for private practices are likely misguided. PMID- 25124876 TI - Flexible sigmoidoscopy screening reduces colorectal cancer incidence and deaths, study shows. PMID- 25124877 TI - Unusually severe hypophosphatemic rickets caused by a novel and complex re arrangement of the PHEX gene. AB - X-linked hypophosphatemia (XLH) is caused by mutations in PHEX. Several other genetic forms of hypophosphatemia have also been described. These disorders share variable clinical presentation ranging from mild hypophosphatemia to severe lower extremity bowing. We report on a 43-year-old woman with short stature, painful leg deformities, and poor dentation. Her biochemical profile showed hypophosphatemia with renal phosphate wasting. Due to unusually severe clinical presentation and absence of mutations in Sanger sequencing of the PHEX gene, quantitative multiplex ligation-dependent probe amplification was performed. A large deletion within the PHEX gene encompassing exons 8 to 11 was identified. We generated a specific junction fragment using long-range PCR and sequenced the junction fragment to determine the exact deletion breakpoints. We found a heterozygous novel complex re-arrangement involving gross deletions, insertions, and inversion of PHEX (hg19:g.22,115,003_22,141,395del;g:22,145,536_22,150,789delinsCins22,114,640_22,1 4,698invinsA). Thus, the complex re-arrangement including a deletion of coding exons 8 to 11 of the PHEX can be regarded as the cause of XLH in the patient reported here. Phosphate and active vitamin D treatment was initiated with subsequent relief in bone pain and physical improvement. This report expands the spectrum of clinical severity underlying genetic defects in XLH and highlights the importance of conventional medical therapy even at adult age. Furthermore, our findings underscore the importance of search for gene deletions in patients with suspected XLH. PMID- 25124878 TI - Impact of the information age on residency training: communication, access to public information, and clinical care. AB - Access to technology in practice helps physicians manage information, communicate, and research topics; however, those in training receive almost no formal preparation for integrating web-based technologies into practice. One reason for this is that many faculty-aside from junior faculty or those in recent generations-did not grow up using Internet communication, may use it minimally, if at all, in their own practices, and may know little about its forms and varieties. This report presents a case to illustrate how these disparities may play out in the supervisory situation and makes suggestions about helping supervisors integrate technology-awareness into their teaching. PMID- 25124879 TI - Improved Attitudes to Psychiatry: A Global Mental Health Peer-to-Peer E-Learning Partnership. AB - OBJECTIVE: Health links aim to strengthen healthcare systems in low and middle income countries through mutual exchange of skills, knowledge, and experience. However, student participation remains limited despite growing educational emphasis upon global health. Medical students continue to report negative attitudes to psychiatry in high-income countries, and in Somaliland, the lack of public sector psychiatrists limits medical students' awareness of mental healthcare. The authors describe the design, implementation, and mixed-methods analysis of a peer-to-peer psychiatry e-learning partnership between UK and Somaliland students arising from a global mental health link between the two countries. METHODS: Medical students at King's College London and Hargeisa and Amoud universities, Somaliland, were grouped into 24 pairs. Participants aimed to complete ten fortnightly meetings to discuss psychiatry topics via the website MedicineAfrica. Students completed initial and final evaluations including Attitudes toward Psychiatry (ATP-30) questions, a stigma questionnaire, and brief evaluations after each meeting. RESULTS: Quantitative findings demonstrated that enjoyment, interest, and academic helpfulness were rated highly by students in Somaliland and moderately by students in the UK. Somaliland students' attitudes to psychiatry were significantly more positive post-participation, whereas UK students' attitudes remained stable. Qualitative findings identified more gains in factual knowledge for Somaliland students, whereas UK students reported more cross-cultural learning. Reasons for non-completion and student-suggested improvements emphasized the need to ensure commitment to the program by participants. CONCLUSIONS: This partnership encouraged students to consider global mental health outside the standard medical education environment, through an e-learning format solely utilizing existing resources. This new approach demonstrates potential benefits to students in contrasting locations of brief, focused online peer-to-peer education partnerships, expanding the scope of health links to the medical professionals of the future. PMID- 25124881 TI - General psychiatric residents and corrections: moving forensic education beyond the classroom. AB - Mental illness in the criminal justice system is one of the most important and underserved public health challenges in psychiatry today, but few general psychiatry residency programs offer clinical education in correctional psychiatry. Developing such rotations might seem intimidating to educational leaders unfamiliar with the criminal justice system, but a variety of potential solutions exist for residency programs to offer this increasingly important clinical training. PMID- 25124880 TI - Understanding the dynamics of change and the impact on psychiatric education. AB - Academic departments of psychiatry are experiencing unprecedented changes that are difficult and challenging for faculty and administrators. This article examines the factors that influence change and the barriers to effective change. The author reviewed the business literature on change in organizations and examined the psychodynamic factors that mediate individual and organizational response to change. Several business models for effective change management exist and can be utilized by psychiatric educators. The psychodynamic models of change are useful for understanding the psychological impact of change on organizations and individuals. Effective management of change requires careful attention to the goals of the organization, development of a detailed plan to implement change, adequate resources to carry out the change, effective leadership and communication, and contingency plans for unforeseen events. Individual and organizational needs must also be considered. A model for dealing with change in education is presented. PMID- 25124875 TI - MicroRNA-145: a potent tumour suppressor that regulates multiple cellular pathways. AB - MicroRNAs are endogenous, small (18-25 nucleotides) non-coding RNAs, which regulate genes expression by directly binding to the 3'-untranslated regions of the target messenger RNAs. Emerging evidence shows that alteration of microRNAs is involved in cancer development. MicroRNA-145 is commonly down-regulated in many types of cancer, regulating various cellular processes, such as the cell cycle, proliferation, apoptosis and invasion, by targeting multiple oncogenes. This review aims to summarize the recent published literature on the role of microRNA-145 in regulating tumourigenesis and progression, and explore its potential for cancer diagnosis, prognosis and treatment. PMID- 25124883 TI - No chromosome but image duplication. PMID- 25124882 TI - Abdominal injuries in a low trauma volume hospital--a descriptive study from northern Sweden. AB - BACKGROUND: Abdominal injuries occur relatively infrequently during trauma, and they rarely require surgical intervention. In this era of non-operative management of abdominal injuries, surgeons are seldom exposed to these patients. Consequently, surgeons may misinterpret the mechanism of injury, underestimate symptoms and radiologic findings, and delay definite treatment. Here, we determined the incidence, diagnosis, and treatment of traumatic abdominal injuries at our hospital to provide a basis for identifying potential hazards in non-operative management of patients with these injuries in a low trauma volume hospital. METHODS: This retrospective study included prehospital and in-hospital assessments of 110 patients that received 147 abdominal injuries from an isolated abdominal trauma (n = 70 patients) or during multiple trauma (n = 40 patients). Patients were primarily treated at the University Hospital of Umea from January 2000 to December 2009. RESULTS: The median New Injury Severity Score was 9 (range: 1-57) for 147 abdominal injuries. Most patients (94%) received computed tomography (CT), but only 38% of patients with multiple trauma were diagnosed with CT < 60 min after emergency room arrival. Penetrating trauma caused injuries in seven patients. Solid organ injuries constituted 78% of abdominal injuries. Non-operative management succeeded in 82 patients. Surgery was performed for 28 patients, either immediately (n = 17) as result of operative management or later (n = 11), due to non-operative management failure; the latter mainly occurred with hollow viscus injuries. Patients with multiple abdominal injuries, whether associated with multiple trauma or an isolated abdominal trauma, had significantly more non-operative failures than patients with a single abdominal injury. One death occurred within 30 days. CONCLUSIONS: Non-operative management of patients with abdominal injuries, except for hollow viscus injuries, was highly successful in our low trauma volume hospital, even though surgeons receive low exposure to these patients. However, a growing proportion of surgeons lack experience in decision-making and performing trauma laparotomies. Quality assurance programmes must be emphasized to ensure future competence and quality of trauma care at low trauma volume hospitals. PMID- 25124885 TI - The effect of the laryngeal tie-forward procedure and soft palate cautery on nasopharyngeal diameter in horses. AB - The laryngeal tie-forward (LTF) procedure has been shown to move the larynx rostrally and dorsally whilst repositioning the basihyoid bone caudally and dorsally. Other studies have shown that the position of the hyoid bones influences the size of the nasopharynx. The effect of the LTF procedure on the size of the nasopharynx is unknown. It was hypothesised that the LTF procedure would result in a decrease in dorsoventral nasopharyngeal diameter. Twenty-five thoroughbred horses which underwent LTF with or without soft palate cautery (LTF+/-SPC) for treatment of dorsal displacement of the soft palate were included in this study. Preoperative and postoperative lateral radiographs were used to determine changes in laryngohyoid position and nasopharyngeal diameter. The LTF+/ SPC procedure resulted in a significant reduction (14-17 per cent) in dorsoventral nasopharyngeal diameter (P<0.001). The LTF procedure decreases nasopharyngeal diameter. The impact on upper respiratory tract function during exercise remains unclear. PMID- 25124884 TI - Qualitative and quantitative analysis of a group of volatile organic compounds in biological samples by HS-GC/FID: application in practical cases. AB - A simple and sensitive procedure, using n-propanol as internal standard (IS), was developed and validated for the qualitative and quantitative analysis of a group of 11 volatile organic substances with different physicochemical properties (1 butanol, 2-propanol, acetaldehyde, ethyl acetate, acetone, acetonitrile, chloroform, diethyl ether, methanol, toluene and p-xylene) in whole blood, urine and vitreous humor. Samples were prepared by dilution with an aqueous solution of internal standard followed by Headspace Gas Chromatography with a Flame ionization Detector (HS GC-FID) analysis. Chromatographic separation was performed using two capillary columns with different polarities (DB-ALC2: 30m*0.320mm*1.2MUm and DB-ALC1: 30m*0.320mm*1.8MUm), thus providing a change in the retention and elution order of volatiles. This dual column confirmation increases the specificity, since the risk of another substance co-eluting at the same time in both columns is very small. The method was linear from 5 to 1000mg/L for toluene and p-xylene, 50-1000mg/L for chloroform, and 50-2000mg/L for the remaining substances, with correlation coefficients of over 0.99 for all compounds. The limits of detection (LOD) ranged 1 to 10mg/L, while the limits of quantification (LOQ) ranged from 2 to 31mg/L. The intra-day precision (CV<6.4%), intermediate precision (CV<7.0%) and accuracy (relative error +/-10%) of the method were in conformity with the criteria normally accepted in bioanalytical method validation. The method developed has been applied to forensic cases, with the advantages that it uses a small sample volume and does not require any extraction procedure as it makes use of a headspace injection technique. PMID- 25124887 TI - Putative candidate genes for canine hypoadrenocorticism (Addison's disease) in multiple dog breeds. PMID- 25124886 TI - Weather and soil type affect incidence of fasciolosis in dairy cow herds. AB - Fasciolosis caused by Fasciola hepatica is generally a subclinical infection of dairy cows and can result in marked economic losses on Irish dairy farms. This study investigated the exposure to F hepatica in 237 dairy cow herds, using an in house antibody-detection ELISA applied to bulk tank milk (BTM) samples collected in the autumn of 2012. A total of 364 BTM samples were collected from 237 different herds, with 127 farmers submitting BTM samples in two consecutive months. Analysis of the BTM samples indicated that 67 per cent (n= 159) of the dairy herds had been exposed to F hepatica. Rainfall, temperature and soil types were significantly different between the exposed and non-exposed herds (P<0.05), highlighting the role of these variables to the exposure to F hepatica. Among the 127 herds that provided two monthly milk samples, 83 herds were exposed to F hepatica and 82 increased their F hepatica antibody levels at the later sampling time (P<0.01).The findings of this study confirm the high prevalence of F hepatica antibodies in Irish dairy herds and show the rise in antibody levels during autumn. This study is the first step towards assessing the spatiotemporal pattern of fasciolosis in dairy herds in Ireland. PMID- 25124889 TI - Seeking a measure of clinically meaningful change in ALS. AB - We sought to identify a method to assess 'clinically meaningful change' perceived by patients, caregivers and clinical raters in relation to changes in ALSFRS-R scores at three-month intervals. In this five-site study, 81 patient-caregiver dyads were interviewed at baseline, three, and six months to assess changes in ALSFRS-R in relation to perceived occurrence of change, its magnitude and impact. Ratings by patients, caregivers and clinical raters were analyzed over three month intervals within and between respondent groups. We found that patients, clinical raters, and caregivers agreed about 80% of the time about whether change occurred, and in what direction, on each of three visits. The perceived magnitude of change for the four domains measured by the ALSFRS-R was correlated with ratings of impact within respondent groups and across time. We also found moderate associations between changes in ALSFRS-R domain scores and judgments of symptom impact as rated by patient, caregiver and clinical rater. Independent measures (Quality of Life, Goal Assessment Scaling) showed no consistent correlations with ALSFRS-R change scores. In conclusion, the use of scales to assess the perceived magnitude and impact of change corresponding with the domains of the ALSFRS-R may be a step towards understanding of the clinical meaning of changes in that measure. PMID- 25124888 TI - Comparison of clinical outcomes for 40 necrotic immature permanent incisors treated with calcium hydroxide or mineral trioxide aggregate apexification/apexogenesis. AB - BACKGROUND/PURPOSE: Traumatic injury often results in pulp necrosis of immature permanent incisors in children. This study compared clinical outcomes for 40 necrotic immature permanent incisors treated with calcium hydroxide [Ca(OH)2] or mineral trioxide aggregate (MTA) apexification/apexogenesis. METHODS: Forty necrotic open-apex incisors from 40 children aged 6.5-10 years were divided evenly into four groups with each group containing teeth of similar type and similar root apex width in patients of similar age. Group 1 incisors were treated with ultrasonic filing and MTA placement; Group 2 were treated with ultrasonic filing and Ca(OH)2 medication; Group 3 were treated with hand filing and MTA placement; and Group 4 were treated with hand filing and Ca(OH)2 medication. RESULTS: Group 1 incisors needed the shortest mean duration (5.4 +/- 1.1 weeks) for apical hard tissue barrier formation, followed by Group 3 incisors (7.8 +/- 1.8 weeks), Group 2 incisors (11.3 +/- 1.3 weeks), and Group 4 incisors (13.1 +/- 1.5 weeks). Group 1 incisors had a significantly shorter mean elongated root length (2.1 +/- 0.2 mm) after treatment than Group 2 incisors (3.5 +/- 0.3 mm, p < 0.001), and Group 3 incisors had a significantly shorter mean elongated root length (2.1 +/- 0.1 mm) after treatment than Group 4 incisors (3.7 +/- 0.3 mm, p < 0.001). CONCLUSION: Necrotic open-apex incisors treated with ultrasonic filing plus MTA placement need the shortest mean duration for apical hard tissue barrier formation. For elongation of apical root length, Ca(OH)2 apexification/apexogenesis is better than MTA apexification/apexogenesis, regardless if either ultrasonic or hand filing are used. PMID- 25124890 TI - A genomic profile of the immune response to stroke with implications for stroke recovery. AB - OBJECTIVES: The objectives of this study were to determine the change in gene expression between two time points following stroke and to identify biomarkers of stroke recovery through gene expression profiling and pathway analysis. METHODS: Peripheral blood was collected from 34 ischemic stroke patients (confirmed by magnetic resonance imaging) >=18 years of age, within 24 hr of symptom onset and 24-48 hr later, and from healthy controls. The Modified Rankin Scale (MRS) was used to determine 30-day recovery. Total RNA was extracted from whole blood in Paxgene RNA tubes, amplified, and hybridized to Illumina HumanRef-8v2 bead chips. Gene expression was compared in a univariate manner between stroke patients at both time points and good versus bad outcome using t-test in GeneSpring. Inflation of Type 1 error was corrected by false discovery rate (FDR), and Ingenuity Systems Pathway analysis (IPA) was performed. A secondary validation cohort was recruited from a local hospital. RESULTS: Three genes were significantly downregulated over time (LY96, IL8, and SDPR; FDR corrected p < .05). This finding was confirmed in a validation cohort of stroke patients (n = 8). IPA revealed cytotoxic T-lymphocyte antigen 4 (CTLA4) signaling was the most significant pathway present in the peripheral whole blood of stroke patients 24 48 hr after onset. When controlling for age and National Institutes of Health Stroke Scale score, high baseline expression of TLR2 and TLR4 significantly predicted worse scores on the MRS. CONCLUSION: CTLA4 signaling is a novel pathway for the study of stroke-induced immune suppression. Markers of immune dysfunction early after stroke may prove useful for identifying patients with increased risk of poor recovery. PMID- 25124891 TI - Association of androgen-deprivation therapy with excess cardiac-specific mortality in men with prostate cancer. AB - OBJECTIVES: To determine if androgen-deprivation therapy (ADT) is associated with excess cardiac-specific mortality (CSM) in men with prostate cancer and no cardiovascular comorbidity, coronary artery disease risk factors, or congestive heart failure (CHF) or past myocardial infarction (MI). PATIENTS AND METHODS: In all, 5077 men (median age 69.5 years) with cT1c-T3N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant ADT (median duration 4 months) between 1997 and 2006. Fine and Gray competing risks analysis evaluated the association of ADT with CSM, adjusting for age, year of brachytherapy, and ADT treatment propensity score among men in groups defined by cardiac comorbidity. RESULTS: After a median follow-up of 4.8 years, no association was detected between ADT and CSM in men with no cardiac risk factors (1.08% at 5 years for ADT vs 1.27% at 5 years for no ADT, adjusted hazard ratio (AHR) 0.83; 95% confidence interval (CI), 0.39-1.78; P = 0.64; n = 2653) or in men with diabetes mellitus, hypertension, or hypercholesterolaemia (2.09% vs 1.97%, AHR 1.33; 95% CI 0.70-2.53; P = 0.39; n = 2168). However, ADT was associated with significantly increased CSM in men with CHF or MI (AHR 3.28; 95% CI 1.01-10.64; P = 0.048; n = 256). In this subgroup, the 5-year cumulative incidence of CSM was 7.01% (95% CI 2.82-13.82%) for ADT vs 2.01% (95% CI 0.38-6.45%) for no ADT. CONCLUSION: ADT was associated with a 5% absolute excess risk of CSM at 5 years in men with CHF or prior MI, suggesting that administering ADT to 20 men in this potentially vulnerable subgroup could result in one cardiac death. PMID- 25124892 TI - Estimation of contaminant subslab concentration in petroleum vapor intrusion. AB - In this study, the development and partial validation are presented for an analytical approximation method for prediction of subslab contaminant concentrations in PVI. The method involves combining an analytic approximation to soil vapor transport with a piecewise first-order biodegradation model (together called the Analytic Approximation Method, including Biodegradation, AAMB), the result of which calculation provides an estimate of contaminant subslab concentrations, independent of building operation conditions. Comparisons with three-dimensional (3-D) simulations and another PVI screening tool, BioVapor, show that the AAMB is suitable for application in a scenario involving a building with an impermeable foundation surrounded by open ground surface, where the atmosphere is regarded as the primary oxygen source. Predictions from the AAMB can be used to determine the required vertical source-building separation, given a subslab screening concentration, allowing identification of buildings at risk for PVI. This equation shows that the "vertical screening distance" suggested by U.S. EPA is sufficient in most cases, as long as the total petroleum hydrocarbon (TPH) soil gas concentration at the vapor source does not exceed 50-100mg/L. When the TPH soil gas concentration of the vapor source approaches a typical limit, i.e. 400mg/L, the "vertical screening distance" required would be much greater. PMID- 25124894 TI - Characterization of a novel intrinsic luminescent room-temperature ionic liquid based on [P6,6,6,14 ][ANS]. AB - Intrinsically luminescent room-temperature ionic liquids (RTILs) can be prepared by combining a luminescent anion (more common) or cation with appropriate counter ions, rendering new luminescent soft materials. These RTILs are still new, and many of their photochemical properties are not well known. A novel intrinsic luminescent RTIL based on the 8-anilinonaphthalene-1-sulfonate ([ANS]) anion combined with the trihexyltetradecylphosphonium ([P6,6,6,14 ]) cation was prepared and characterized by spectroscopic techniques. Detailed photophysical studies highlight the influence of the ionic liquid environment on the ANS fluorescence, which together with rheological and (1) H NMR experiments illustrate the effects of both the viscosity and electrostatic interactions between the ions. This material is liquid at room temperature and possesses a glass transition temperature (Tg ) of 230.4 K. The fluorescence is not highly sensitive to factors such as temperature, but owing to its high viscosity, dynamic Stokes shift measurements reveal very slow components for the IL relaxation. PMID- 25124893 TI - Parallel evolution of a self-signal: humans and new world monkeys independently lost the cell surface sugar Neu5Gc. AB - Human sialic acid biology is unusual and thought to be unique among mammals. Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self. Losing this sugar changed how humans interact with some of our deadliest pathogens: malaria, influenza, and streptococcus among others. We show that the New World monkeys, comprising the third of all primate species, have human-like sialic acid biology. They have lost Neu5Gc because of an independent CMAH inactivation ~30 million years ago (mya) (compared to ~3 mya in hominids). This parallel loss of Neu5Gc opens sialic acid biology to comparative phylogenetic analysis and reveals an unexpected conservation priority. New World monkeys risk infection by human pathogens that can recognize cells in the absence of Neu5Gc. This striking molecular convergence provides a mechanism that could explain the long-standing observation that New World monkeys are susceptible to some human diseases that cannot be transmitted to other primates. PMID- 25124895 TI - Molecular signals regulating translocation and toxicity of graphene oxide in the nematode Caenorhabditis elegans. AB - Both in vitro and in vivo studies have demonstrated the toxic effects of graphene oxide (GO). However, the molecular basis for the translocation and toxicity of GO is still largely unclear. In the present study, we employed an in vivo Caenorhabditis elegans assay system to identify molecular signals involved in the control of the translocation and toxicity of GO. We identified 7 genes whose mutations altered both the translocation and toxicity of GO. Mutations of the hsp 16.48, gas-1, sod-2, sod-3, and aak-2 genes caused greater GO translocation into the body and toxic effects on both primary and secondary targeted organs compared with wild type; however, mutations of the isp-1 and clk-1 genes resulted in significantly decreased GO translocation into the body and toxicity on both primary and secondary targeted organs compared with wild-type. Moreover, mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused increased intestinal permeability and prolonged mean defecation cycle length in GO-exposed nematodes, whereas mutations of the isp-1 and clk-1 genes resulted in decreased intestinal permeability in GO-exposed nematodes. Therefore, for the underlying mechanism, we hypothesize that both intestinal permeability and defecation behavior may have crucial roles in controlling the functions of the identified molecular signals. The molecular signals may further contribute to the control of transgenerational toxic effects of GO. Our results provide an important insight into understanding the molecular basis for the in vivo translocation and toxicity of GO. PMID- 25124898 TI - [Analysis of the curative effect of ABO-incompatible liver transplantation in the treatment in patients with acute severe liver disease]. AB - OBJECTIVE: To analyze and evaluate the clinical effect of ABO-incompatible liver transplantation in the treatment of acute severe liver disease. METHODS: A retrospective clinical study was conducted. The clinical data of 4 136 patients undergoing orthotopic liver transplantation in Organ Transplantation Center of Tianjin First Center Hospital from September 1999 to December 2013 were analyzed. The criteria of patients enrolled were as following: model for end-stage liver disease (MELD) score >= 20, the donor's and recipient's blood types were different, age 18-70 years, and undergone primary non-bypass orthotopic liver transplantation. According to the rate of compliance with the principles of blood transfusion, the cases were divided into two groups: ABO-compatible group (ABO-C group, n=41), ABO-incompatible group (ABO-I group, n=22). The patients in ABO-I group received basiliximab + methylprednisolone for immune induction therapy during operation, basiliximab + tacrolimus + mycophenolate + cortisol as quadruple immunosuppressive regimen after operation. They also received subcutaneous injection of low molecular heparin for anticoagulant therapy after operation, and oral warfarin or aspirin and clopidogrel bisulfate instead after 7 days. They also received routine alprostadil after operation. The remaining treatment was the same as that of ABO-C group. The clinical data, postoperative complications, rejection and survival rates of two groups were statistically analyzed. RESULTS: There were no significant differences in gender, age, MELD score, complicated with tumor, quality of donor liver, length of cold preservation of donor liver, duration of operation, and blood loss during operation between ABO-C and ABO-I groups. Number of splenectomy during operation was significantly higher in ABO-I group than that in ABO-C group (5 cases vs. 1 case, chi2 = 4.687, P=0.030). The 3-month, 6-month, 1-year, 3-year and 5-year survival rates of ABO-C group were 89.5%, 78.3%, 72.5%, 69.1% and 61.8%, respectively, while those of ABO-I group were 78.9%, 72.9%, 65.6%, 56.2% and 46.8%, respectively. There was no significant difference in the cumulative survival rate between two groups (Log Rank, chi2 = 0.647, df=1, P=0.421). The postoperative infection rate in ABO-I group was significantly higher than that of ABO-C group [63.6% (14/22) vs. 31.7% (13/41), chi2 = 5.960, P=0.015]. There were no significant difference in postoperative complications of biliary tract [22.7% (5/22) vs. 12.2% (5/41), chi2 = 0.531, P=0.466], vascular complications [31.8% (7/22) vs. 12.2% (5/41), chi2 = 2.416, P=0.120], or rejection as diagnosed by pathology [22.7% (5/22) vs. 9.8% (4/41), chi2 = 1.051, P=0.305] between ABO-I and ABO-C groups. CONCLUSIONS: Although ABO-incompatible liver transplantation was followed by higher postoperative infection rate and perioperative mortality, ABO incompatible liver transplantation can still be used to save the patient with acute severe liver disease as there is a shortage of compatible donor at present. PMID- 25124896 TI - P2X7 is involved in the anti-inflammation effects of levobupivacaine. AB - BACKGROUND: We sough to elucidate whether purinergic P2X7 receptor is actively involved in the effects of levobupivacaine on inhibiting microglia activation. MATERIALS AND METHODS: Microglia were treated with lipopolysaccharide (LPS, 50 ng/mL), LPS plus levobupivacaine (50 MUM), or LPS plus levobupivacaine plus the P2X7 receptor agonist Bz-ATP (100 MUM) and denoted as the LPS, LPS + Levo, and LPS + Levo + Bz-ATP group, respectively. Microglia activation was measured by assaying inflammatory molecules expression. Microglia activation was also measured by assaying neuronal cell viability using coculture of microglia and neurons, as activated microglia may cause neuron injury. We also measured the levels of P2X7 receptor activation in microglia using ethidium uptake assay. RESULTS: Our data confirmed the effects of levobupivacaine on inhibiting inflammatory molecules upregulation in activated microglia, as the concentrations of interleukin (IL)-1beta, tumor necrosis factor alpha, IL-6, and macrophage inflammatory protein 2, of the LPS + Levo group were significantly lower than those of the LPS group (all P < 0.05). Moreover, Bz-ATP significantly abrogated the inhibitory effects of levobupivacaine, as concentrations of IL-1beta, tumor necrosis factor alpha, IL-6, and macrophage inflammatory protein 2 of the LPS + Levo + Bz-ATP group were significantly higher than those of the LPS + Levo group (all P < 0.05). In contrast, neuronal cell viability of the LPS + Levo group was significantly higher than those of the LPS and LPS + Levo + Bz-ATP groups (P = 0.012 and 0.002). Moreover, levels of P2X7 receptor activation of the LPS and LPS + Levo + Bz-ATP groups were significantly higher than that of the LPS + Levo group (P = 0.003 and 0.006). CONCLUSIONS: P2X7 receptor is involved in the effects of levobupivacaine on inhibiting microglial activation. PMID- 25124897 TI - Prophylactic fasciotomy in a porcine model of extremity trauma. AB - BACKGROUND: Extremity injury, with concomitant hemorrhagic shock, can result in ischemia-reperfusion injury and the formation of compartment syndrome requiring fasciotomy. As the benefit of prophylactic fasciotomy is unclear, the objective of this study is to determine the functional recovery of an ischemic limb with hemorrhagic shock after prophylactic fasciotomy. MATERIAL AND METHODS: Yorkshire swine underwent 35% blood volume hemorrhage, followed by 1, 3, and 6 h of ischemia (n = 17; 1HR, 3HR, and 6HR) via iliac artery occlusion followed by repair and reperfusion. A second cohort (n = 18) underwent fasciotomy of the anterior compartment of the hind limb following vascular repair (1HR-F, 3HR-F, and 6HR-F). Compartment pressures, measures of electromyographic (EMG) recovery, and a validated gait score (modified Tarlov) were performed throughout a 14-d survival period. RESULTS: Increasing ischemic intervals resulted in incremental increases in compartment pressure (P < 0.05), although the mean did not exceed 30 mm Hg. EMG studies did not show a significant improvement comparing the 3HR with 6HR groups. There was a significant improvement in the EMG studies within the 3HR F, when compared with 6HR-F. There was a trend toward sensory improvement between the 3HR-F and 3HR groups. However, this did not translate to a difference in functional outcome as measured by the Tarlov gait score. CONCLUSIONS: Within this swine model of hemorrhagic shock and hind limb ischemia, the use of prophylactic fasciotomies did not improve functional outcome. PMID- 25124899 TI - [Recombinant Trichinella spiralis-53000 protein alleviates liver damage due to lipopolysaccharides via M2 macrophage activation]. AB - OBJECTIVE: To evaluate if recombinant Trichinella spiralis-53 000 protein (rTsP53) could alleviate liver damage caused by lipopolysaccharides (LPS) via M2 macrophage activation. METHODS: Sixty male BALB/c mice were randomly divided into LPS group, LPS + phosphate buffer saline (PBS) group and rTsP53 intervention group by random number table, with 20 mice in each group. Intraperitoneal injection of 15 MUg/kg LPS was performed for all the mice in the three groups after 8 hours of fasting. The mice in LPS + PBS group were injected with PBS after 1 hour of LPS injection. The mice in the rTsP53 intervention group were injected with rTsP53 (5 mg/kg) after 1 hour of LPS injection. After 48 hours all the mice were sacrificed. Peritoneal macrophages were harvested and flow cytometry (FCM) was used to detect markers CCR7 (M1) and CD206 (M2) of macrophages. Hepatic tissue was harvested for pathological study after hematoxylin-eosin (HE) staining, and double staining immunofluorescence was used to detect F4/80+ HLA-DR+ and F4/80+ CD163+. Peripheral blood serum was harvested to detect the levels of aspartate transaminase (AST) and alanine transaminase (ALT). RESULTS: Compared with LPS and LPS + PBS groups, survival rate of mice of rTsP53 intervention group was significantly elevated (90% vs. 25%, 30%, both P<0.01), and the pathological injury of the liver was significantly ameliorated, and the hepatic structure was better preserved. The transaminase in rTsP53 intervention group was significantly lower than that of LPS and LPS + PBS groups (ALT: 97.7 +/- 8.5 U/L vs. 181.7 +/- 19.5 U/L, 173.7 +/- 17.2 U/L; AST: 142.7 +/- 12.1 U/L vs. 235.7 +/- 9.9 U/L, 213.7 +/- 6.7 U/L, all P<0.05), FITC-CD206+ proportion of peritoneal macrophage was significantly higher [(17.75 +/- 0.30)% vs. (1.38 +/- 0.13)%, (1.36 +/- 0.05)%, both P<0.05] while PE-CCR7(+) proportion [(6.89 +/- 0.11)% vs. (15.30 +/- 0.64)%, (14.96 +/- 0.93)%, both P<0.05] was significantly lower. Fluorescence intensity of macrophages with F4/80+ CD163+ double staining for liver sections was significantly increased (0.36 +/- 0.01 vs. 0.29 +/- 0.02, 0.31 +/- 0.01, both P<0.05), while there was no significant difference in the fluorescence intensity of macrophages with F4/80+ HLA-DR+ double staining (0.30 +/- 0.01 vs. 0.30 +/- 0.02, 0.31 +/-0.01, both P>0.05). There was no significant difference of above results between LPS group and LPS + PBS group (all P>0.05). CONCLUSIONS: rTsP53 could ameliorate liver damage caused by LPS and improve animal's survival via the activation of M2 macrophage. PMID- 25124900 TI - [The value of the baseline MELD scores, MELD-Na scores and iMELD scores in short term prognosis in hepatitis B virus related acute-on-chronic liver failure patients]. AB - OBJECTIVE: To explore the function of the baseline model for end-stage liver disease (MELD) scores, MELD-Na scores and iMELD scores in short-term prognosis in the initial treatment of hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF) patients. METHODS: 232 HBV-related ACLF patients who received initial treatment in 302 Military Hospital of China from January 2011 to January 2013 were enrolled in this prospective clinical follow-up. The relationship between the baseline MELD scores, MELD-Na scores, iMELD scores and clinical outcomes were analyzed, and the value of these three models for short term prognosis was assessed. RESULTS: Finally the 12-week clinical follow-up was completed in 191 patients, with the completion rate of 82.33%. Eighty-five patients died, with the fatality rate of 44.50%. Compared with the survival group, in non-survival group, the baseline of MELD scores (26.65 +/- 7.75 vs. 21.19 +/- 5.42, t=-5.720, P=0.000), MELD-Na scores (29.16 +/- 11.35 vs. 21.72 +/- 6.33, t=-5.729, P=0.000), iMELD scores (47.19 +/- 10.96 vs. 38.02 +/- 7.01, t= 7.011, P=0.000), total bilirubin (TBil: 374.3 +/- 150.1 MUmol/L vs. 305.5 +/- 147.1 MUmol/L, t=-3.182, P=0.002), creatinine (Cr: 110.7 +/- 90.1 MUmol/L vs. 71.1 +/- 35.1 MUmol/L, t=-4.157, P=0.000) and international normalized ratio (INR: 2.3 +/- 0.9 vs. 2.0 +/- 0.6, t=-2.754, P=0.006) were significantly increased, but the baseline of serum Na+ (132.8 +/- 6.1 mmol/L vs. 136.7 +/- 5.1 mmol/L, t=4.861, P=0.000) was significantly lowered. It was shown by Spearman correlation analysis that the baseline MELD scores, MELD-Na scores and iMELD scores all had positive correlation with the short-term prognosis of patients (r value was 0.398, 0.404, and 0.470, respectively, all P=0.000), the baseline of serum Na+ had a negative correlation with the short-term prognosis of patients (r=-0.365, P=0.000). It was shown by receiver operating characteristic curve (ROC curve) that the cut-off scores of the baseline of MELD scores, MELD-Na scores and iMELD scores were 25.07, 25.43 and 43.11 respectively, and the area under ROC curve (AUC) of the baseline of MELD scores, MELD-Na scores and iMELD scores were 0.731, 0.735 and 0.773, respectively. The sensitivity of the three models was 55.3%, 57.7%, 63.5%, and the specificity was 84.9%, 84.0%, 84.9% respectively. The value of the three models had no difference in short-term prognostic prediction. According to the respective cut-off score, the three prediction models were divided into four groups, and all of them had differences in fatality rate on the whole (chi2 for MELD scores was 34.740, P=0.000; chi2 for MELD-Na scores was 36.861, P=0.000; chi2 for iMELD scores was 50.127, P=0.000). The mortality was elevated gradually as the equation scores increased. CONCLUSIONS: The baseline of MELD scores, MELD-Na scores and iMELD scores can predict well the short-term prognosis of the initial treatment in HBV-related ACLF patients, and have relatively good clinical value for guiding therapy. PMID- 25124901 TI - [Ventilator bundle treatment of acute respiratory distress syndrome and its correlation with biomarkers of inflammation]. AB - OBJECTIVE: To observe the levels of blood soluble urokinase plasminogen activator receptor (suPAR), receptor of advanced glycation end products (RAGE), procalcitonin (PCT) and C-reactive protein (CRP), and to investigate the effect of ventilator bundle (VB) on prognosis of patients with acute respiratory distress syndrome (ARDS). METHODS: A prospective controlled study was conducted. A total of 54 cases of ARDS patients admitted to Department of Critical Care Medicine of the Second Hospital of Lanzhou University who received treatment of invasive mechanical ventilation between January 2013 and December 2013 were enrolled. All of the patients were given VB, and then divided into completely dependent group (VB group, n=29) and non-completely dependent group (NVB group, n=25) according to the dependence. The mechanical ventilation time, intensive care unit (ICU) length of stay, the incidence of ventilator associated pneumonia (VAP), the incidence of complications and 28-day mortality rate were compared between two groups. The blood suPAR, RAGE, PCT and CRP levels before and after treatment were determined. The correlations between oxygenation index (PaO(2)/FiO(2)) and other variables were analyzed by Pearson correlation and linear regression analysis. RESULTS: (1) There was no significant difference in gender, age, acute physiology and chronic health evaluationII (APACHE II) score and PaO(2)/FiO(2), as well as other basic state between two groups. (2) There was no obvious difference in suPAR, RAGE, PCT and CRP levels before treatment between two groups. The levels of above parameters were significantly decreased after treatment. The blood suPAR and RAGE levels in VB group were significantly decreased compared with those in NVB group [suPAR: 189.87 (135.57) ng/L vs. 309.38 (278.00) ng/L, RAGE: 2.17 (0.75) MUg/L vs. 3.17 (2.64) MUg/L, both P<0.01]. (3) Compared with NVB group, the mechanical ventilation time, ICU length of stay, and the incidence of VAP in VB group were significantly reduced (mechanical ventilation time: 131.52 +/- 44.94 hours vs. 166.28 +/- 38.09 hours, t=-3.039, P=0.004; ICU length of hospital stay: 171.14 +/- 74.25 hours vs. 210.92 +/- 54.89 hours, t=-2.208, P=0.032; incidence of VAP: 17.24% vs. 44.00%, chi2 = 4.611, P=0.041), but 28-day mortality rate (27.59% vs. 36.00%, chi2 = 0.441, P=0.566) and rates of other related complication showed no significant difference between VB group and NVB group. (4) Correlation analysis showed that PaO(2)/FiO(2) was negatively correlated with age (r=-0.290, P=0.033), suPAR (r= 0.898, P=0.000), RAGE (r=-0.898, P=0.000), PCT (r=-0.486, P=0.000) and CRP (r= 0.280, P=0.040). (5) The linear regression analysis showed PaO(2)/FiO(2) and suPAR (t=2.645, P=0.011), RAGE (t=-2.885, P=0.006), PCT (t=2.649, P=0.011) were significantly negatively co-related. CONCLUSIONS: Blood suPAR, RAGE, PCT and CRP levels were correlated with the severity of ARDS patients. Compliance of VB can affect the prognosis of patients with ARDS. The high compliance of patients can significantly decrease the levels of blood pro-inflammatory markers, shorten the mechanical ventilation time and ICU length of stay, reduce the incidence of VAP, and it showed a positive impact on patients' prognosis. PMID- 25124902 TI - [The effect of calpeptin on injury and atrophy of diaphragm under mechanical ventilation in rats]. AB - OBJECTIVE: To investigate the effect of calpeptin on diaphragmatic injury and atrophy under controlled mechanical ventilation in rats. METHODS: A total of 24 SPF Sprague-Dawley (SD) rats were randomly divided into anesthetized control group (CON group), 24-hour controlled mechanical ventilation group (CMV group), and 24-hour CMV + treatment with calpeptin group (CMVC group), with 8 rats in each group. Animals in the CON group received an intraperitoneal injection of pentobarbital sodium without CMV and continuous infusion of pentobarbital sodium. A small-animal ventilator was used for 24 hours in rats of CMV group. Rats of CMVC were treated with a specific calpain inhibitor calpeptin (4 mg/kg). The drug was injected subcutaneously 2 hours before and 8, 15 and 23 hours after mechanical ventilation. Changes in diaphragm ultrastructure, light microscopic picture, and myosin heavy chain (MHC) expression were observed. RESULTS: (1) Alignment of myofilaments and normal Z-band, and the shape of mitochondria were maintained in CON group as revealed by electron microscope. The signs of misalignment of myofibrils, disruption of Z-band and vacuolar mitochondria were found in CMV group, and they were obviously improved in CMVC group. The density of muscle injury (* 10-2/MUm2) in CMV group was significantly higher than that in control group (36.8 +/- 13.7 vs. 6.4 +/- 6.3, t=6.373, P=0.001), and that in CMVC group was significantly lowered (17.6 +/- 9.1 vs. 36.8 +/- 13.7, t=3.694, P=0.002).(2) In CON group, the diaphragm fibers appeared regular in cross section without pathologic change under light microscopy. Fuzzy muscle striations, irregular muscle fibers, centralized nuclei and swelling of capillary endothelial cells were observed in CMV group, while pathological changes in the CMVC group were milder significantly. (3) In CMV group, the density of MHCslow and MHCfast was lower compared with that of CON group, and the gray value was lowered by 61.1% (t=8.138, P=0.001) and 77.1% (t=8.844, P=0.001), respectively, especially in MHCfast. However, the gray values of MHCslow and MHCfast were increased by 1.51 folds (t=4.601, P=0.010), and 1.33 folds (t=2.859, P=0.011), respectively, after treatment with calpeptin, and the elevation was more significantly in MHCslow. CONCLUSIONS: Diaphragmatic injury and atrophy were found after CMV for 24 hours. Calpeptin could reverse the detrimental effects of CMV, and it suggested that calpain plays an important role in modulating the ventilator induced dysfunction of the diaphragm. PMID- 25124903 TI - [Effect of unilateral lung recruitment maneuver on hemodynamics and dead space ratio in pigs with unilateral acute respiratory distress syndrome]. AB - OBJECTIVE: To compare unilateral lung and traditional lung recruitment maneuver (RM) in animals with unilateral acute respiratory distress syndrome (ARDS) by implementing independent lung ventilation, and to explore the rational mechanical ventilation strategy for unilateral lung lesions. METHODS: Healthy hybrid pigs were used as experimental animals, and they were divided into two groups according to random number table method (sealed concealed envelope). There were 20 pigs in each group. According to different methods of lung RM, the conventional mechanical ventilation (i.e. implementing ventilation for both lung by using a ventilator) was performed as control group; the individual lung ventilation (that was, implementing ventilation for both lung individually by using two ventilators) as independent lung ventilation group. The model of left lung ARDS was reproduced, and the respective RM was implemented according to respective method of the two groups. The differences in hemodynamic parameters and dead space ratio (VD/VT) between two groups under the RM pressure of 20, 40, 60 cmH2O (1 cmH2O=0.098 kPa) were observed. RESULTS: (1) Hemodynamics parameters changes: with the increase in RM pressure, the heart rate (HR) in control group showed a tendency of gradual increase, and the level at 60 cmH2O was significantly higher than that at 20 cmH2O (192.65 +/- 22.99 bpm vs. 178.20 +/- 18.25 bpm, P<0.05). Mean arterial pressure (MAP) showed a tendency of gradual decrease, and that at 60 cmH2O was lower significantly than that at 20 cmH2O and 40 cmH2O (78.55+/-25.77 mmHg (1 mmHg=0.133 kPa) vs. 112.40 +/- 10.84 mmHg, 106.15 +/- 13.54 mmHg, both P<0.01). Cardiac output (CO) gradually lowered, and the differences at 20, 40, 60 cmH2O were logistically significant (11.14 +/- 2.65 L/min, 9.56 +/- 2.17 L/min, 6.01 +/- 1.39 L/min, P<0.05 or P<0.01). With an increase in RM pressure, the difference in HR, MAP, CO in independent lung ventilation group were not significant, and the HR at 60 cmH2O was significantly lower than that of the control group (178.20 +/- 18.26 bpm vs. 192.65 +/- 22.99 bpm, P<0.05), and MAP and CO were significantly higher than those of the control group (MAP: 110.80 +/- 11.60 mmHg vs. 78.55 +/- 25.77 mmHg, CO: 9.68 +/- 2.08 L/min vs. 6.01 +/- 1.39 L/min, both P<0.01). (2) VD/VT changes: with an increase in RM pressure, the oxygenation index (PaO2/FiO2) in control group showed a tendency of gradual decrease, and the level at 60 cmH2O was significantly lower than that at 20 cmH2O and 40 cmH2O (126.40 +/- 37.55 mmHg vs. 187.40 +/- 21.66 mmHg, 175.20 +/- 23.00 mmHg, both P<0.01). On the right side, VD/VT showed a tendency of gradual increase, and there was statistical significance in paired comparison among 20, 40, 60 cmH2O (0.52 +/- 0.12, 0.60 +/- 0.15, 0.72 +/- 0.12, P<0.05 or P<0.01). There was no obvious change on the left side. Along with the increase in RM pressure, the PaO2/FiO2 of independent lung ventilation group showed a tendency of gradual increase, and that at 40 cmH2O and 60 cmH2O were significantly higher than that at 20 cmH2O (244.45 +/- 53.93 mmHg, 270.05 +/- 53.42 mmHg vs. 205.65 +/- 31.33 mmHg, P<0.05 and P<0.01), and the level at 20, 40, 60 cmH2O was higher than that of the control group (205.65+/-31.33 vs. 187.40 +/- 21.66, P<0.05; 244.45 +/- 53.93 vs. 175.20 +/- 23.00, P<0.01; 270.05 +/- 53.42 vs. 126.40 +/- 37.55, P<0.01). There were no changes in VD/VT on both sides, and VD/VT on the right side was significantly lower than that of the control group when the inflation pressure was 20, 40, 60 cmH2O (0.38 +/- 0.14 vs. 0.52 +/- 0.12, 0.43 +/- 0.11 vs. 0.60 +/- 0.15, 0.50 +/- 0.13 vs. 0.72 +/- 0.12, all P<0.01). CONCLUSIONS: For severe ARDS caused by single lung injury, implementation of independent lung RM on the basis of independent lung mechanical ventilation for individual lung was significantly superior to the traditional lung RM for the improvement of hemodynamic parameters and VD/VT. PMID- 25124904 TI - [The clinical value of bedside lung ultrasound in the diagnosis of chronic obstructive pulmonary disease and cardiac pulmonary edema]. AB - OBJECTIVE: To study the diagnostic accuracy of bedside lung ultrasound examination in chronic obstructive pulmonary disease (COPD) and cardiac pulmonary edema. METHODS: A prospective pilot and single-blind trial was conducted. A total of 89 patients with respiratory failure admitted to the Department of Critical Care Medicine of Anhui Provincial Hospital from September 2012 to September 2013 were enrolled. There were 32 patients with COPD, 31 patients with cardiac pulmonary edema, 8 patients with interstitial lung disease, 12 with lung infection, and 6 patients with other diseases. Another group of 30 patients without respiratory disease were enrolled as the control group. Bedside lung ultrasound examinations were performed in all patients within 24 hours, and chest radiograph was performed at the same time. The signs to be revealed were the "A" lines or horizontal lines arising from the pleural line, and the comet-tail artifact ("B" lines) arising from the lung wall interface. RESULTS: Of 89 patients, 33 patients were shown a mean of 2.94 +/- 1.87 "A" lines per case with the bedside lung ultrasound, and 38 patients with a mean of 3.27 +/- 1.72 "B" lines per patient. 1.94 +/- 0.96 "A" lines a case and 1.74 +/- 0.82 "B" lines a case in control group. There were significant difference between the test group and control group ("A"line: t=3.835, P=0.000; "B" line: t=6.540, P=0.000). Among 32 cases with COPD, 28 patients had a positive result of "A" line with a coincidence rate of 81.2%. In the 31 patients with cardiac pulmonary edema, 25 patients presented "B" line, with a coincidence rate of 80.6%. The "A" lines or horizontal lines arising from the pleural line showed a sensitivity of 81.30% and a specificity of 87.70% with a positive predictive value (PPV) 78.80% and a negative predictive value (NPV) 89.30% of in the diagnosis of COPD, and the "B" lines showed a sensitivity of 80.60% and a specificity of 77.60% with a PPV of 65.80% and a NPV of 88.20% in the diagnosis of cardiac pulmonary edema. However, X-ray examination showed a sensitivity of 65.50%, a specificity of 86.00%, a PPV of 72.40% and a NPV of 81.70% in the diagnosis of COPD, and it showed a sensitivity of 74.20%, a specificity of 69.00%, a PPV of 56.10% and a NPV of 83.30% in the diagnosis of cardiac pulmonary edema. Bedside ultrasound was highly consistent with X-ray in diagnosis of COPD [area under receiver operating characteristic curve (AUC): 0.833 vs. 0.816, P>0.05], but Kappa value of ultrasound technology "A" line in the diagnosis of COPD was greater than the value of X-ray imaging techniques (0.685 vs. 0.527). There was little diagnostic value of ultrasound "A" line in cardiac pulmonary edema(AUC was 0.305), while the "B" line was superior to X-ray (AUC: 0.888 vs. 0.747, P<0.001), and had a higher Kappa value than the value of X-ray imaging techniques (0.553 vs. 0.481) in cardiac pulmonary edema. CONCLUSIONS: We conclude that bedside ultrasound is cost effective, easy for repeated examination, and suitable for differential diagnosis of lung diseases. It might be useful in screening for COPD and cardiac pulmonary edema. PMID- 25124905 TI - [The protective effect of valproic acid on myocardium in rats with lethal scald injury and its mechanism]. AB - OBJECTIVE: To investigate the protective effects of valproic acid (VPA) on myocardium in rats following lethal burn injury and its mechanism. METHODS: Seventy-eight Sprague-Dawley (SD) rats were randomly assigned to four groups: sham-scald group (n=10), sham-scald + VPA group (n=10), scald group (n=29), and scald + VPA group (n=29). Rats in the latter two groups were subjected to 55% total body surface area (TBSA) third-degree burns by immersing the back of the trunk for 15 seconds, both lower extremities for 15 seconds, and the abdomen for 8 seconds in 80 centigrade water. Sham-scald rats were immersed in 37 centigrade water instead. Rats were then subcutaneously injected with VPA (300 mg/kg) or normal saline as control. Blood of 5 rats in each group was with drawn from the abdominal aorta at 6 hours after injury for measurement of plasma creatine kinase MB (CK-MB) activities; then the rats were sacrificed and heart tissues were harvested for the measurement of acetylated histone H3 and activated caspase-3 by Western Blot. The remaining rats were used for 12-hour survival analysis. RESULTS: Compared with sham-scald group, there was a significant increase in plasma CK-MB activities (5 438.0 +/- 413.6 U/L vs. 2 881.0 +/- 324.8 U/L, P<0.05) and activated caspase-3 protein levels in heart tissue (gray value: 1.75 +/- 0.25 vs. 1.00 +/- 0.18, P<0.05) and an significant decline in the acetylation levels of histone H3 (gray value: 0.55 +/- 0.18 vs. 1.00 +/- 0.20, P<0.05) after major burn injury. VPA treatment significantly reduced the plasma CK-MB activities [(4 018.0 +/- 388.3) U/L], activated caspase-3 protein levels in heart tissue (gray value: 1.33 +/- 0.20), and raised the acetylation levels of histone H3 (gray value: 2.20 +/- 0.23, all P<0.05). Survival analysis by Kaplan-Meier curves showed that the survival was improved after VPA treatment, and the survival rate was increased from 0 to 50% at 12 hours (P<0.05). CONCLUSIONS: VPA can attenuate cardiac injury and improve survival in a rodent model of lethal burn injury. These protective effects may be due to its inhibitory effects on histone deacetylase and caspase-3 activation. PMID- 25124906 TI - [Testify patient's blood electrolyte concentration a tendency to approach that of replacement-fluid in continuous renal replacement therapy]. AB - OBJECTIVE: To prove with mathematical formula that the patient's blood electrolyte concentration shows a tendency to approach that of replacement-fluid after continuous renal replacement therapy (CRRT). METHODS: Electrolyte concentration of plasma, replacement-fluid and returning fluid were compared, and they were labeled as C(blood), C(norm), and C(return) respectively. The "C(return)" was calculated, and the relationship among them was demonstrated with comparison by mathematical formula. At last, according to their relationship, plasma change towards to the replacement fluid was analyzed. RESULTS: It was showed that "C(blood)C(return)>C(norm)", and according the relationship, it was derive that the trend of change in "C(blood)" after circulation for m unit time was "C(blood)1>C(blood)2>C(blood)3> ... >C(blood)m>C(norm)" or "C(blood)1 < C(blood)2 < C(blood)3 < ... < C(blood)m < C(norm)". The plasma electrolyte concentration would close to that of replacement fluid infinitely with the continue of CRRT. CONCLUSIONS: With mathematical model, it is proved that the replacement fluid electrolyte concentration is the final target of the plasma. We must make up the replacement fluid correctly. And this results provide the basis for CRRT treatment of electrolyte disorder. PMID- 25124907 TI - [The clinical application of pulse indicator continuous cardiac output monitoring in early fluid resuscitation for patients with severe acute pancreatitis]. AB - OBJECTIVE: To evaluate the therapeutic effect of early fluid resuscitation under the guidance of pulse indicator continuous cardiac output (PiCCO) on patients with severe acute pancreatitis (SAP). METHODS: Clinical data of 18 SAP patients (research group), who had undergone fluid resuscitation under the guidance of PiCCO in the Department of Critical Care Medicine of the Second Affiliated Hospital of Anhui Medical University from October 2011 to October 2013, were analyzed prospectively. At the same time, clinical data of 25 cases (control group) that had undergone fluid resuscitation without the guidance of PiCCO from January 2009 to September 2011 were collected retrospectively. The volume of fluid and clinical data were compared between two groups. RESULTS: During the first 6 hours, 0-24 hours, 24-48 hours, and 0-72 hours after intensive care unit (ICU) admission, the research group received larger volume of fluid than that of the control group (2 133 +/- 1 593 mL vs. 1 024 +/- 421 mL, t=3.337, P=0.002; 5 960 +/- 2 951 mL vs. 3 767 +/- 854 mL, t=3.531, P=0.001; 4 709 +/- 1 508 mL vs. 3 863 +/- 1 122 mL, t=2.112, P=0.031; 14 601 +/- 5 095 mL vs. 11 409 +/- 2 667 mL, t=2.673, P=0.007). Compared with the control group, the incidence of application of blood purification was lowered [5.56% (1/18) vs. 44.00% (11/25), chi2 = 7.688, P=0.006], the duration of the systemic inflammatory response syndrome (SIRS) was shortened (3.54 +/- 2.44 days vs. 5.62 +/- 3.62 days, t=2.113, P=0.041), acute physiology and chronic health II (APACHEII) score was significantly declined at 24 hours after admission (11 +/- 4 vs. 14 +/- 5, t=2.104, P=0.042), the blood lactic acid was decreased more significantly after 72 hours (3.10 +/- 0.55 mmol/L vs. 2.40 +/- 1.12 mmol/L, t=2.442, P=0.019), and the length of ICU stay was shortened (10 +/- 9 days vs. 20 +/- 10 days, t=3.371, P=0.002) in research group. But there was no significant difference in the percentage of the use of vasoactive drugs [16.67% (3/18) vs. 24.00% (6/25), chi2 =0.340, P=0.560], the incidence of invasive mechanical ventilation [50.00% (9/18) vs. 52.00% (13/25), chi2 = 0.017, P=0.897], 72-hour urea nitrogen changes (-0.33 +/- 4.71 mmol/L vs. 0.09 +/- 5.37 mmol/L, t=0.152, P=0.880), and the percentage of abdominal infection[16.67% (3/18) vs. 16.00% (4/25), chi2 = 0.003, P=0.953] between research group and control group. The mortality in research group was lower than that in control group [5.56% (1/18) vs. 20.00% (5/25)] without statistical difference (chi2 = 1.819, P=0.178). According to the 2012 Atlanta classification, patients were re-evaluated after 48 hours fluid resuscitation. Six patients in research group developed moderately severe acute pancreatitis, and the incidence was significantly higher than that in control group [33.33% (6/18) vs. 8.00% (2/25), chi2 = 4.435, P=0.034]. The time of mean PiCCO installation was 4.5 days in 18 cases of the research group, and no related complications occurred. CONCLUSIONS: The PiCCO device may be a useful adjunct for fluid resuscitation monitoring in patients with SAP within 72 hours. Early fluid resuscitation under the guidance of PiCCO may be helpful in improving tissue perfusion, reducing the application of blood purification, as well as shortening length of ICU stay. This program did not increase the risk of invasive mechanical ventilation, and no obvious change in mortality rate was observed. PMID- 25124908 TI - [The effects of fluid resuscitation on oxygenation index and prognosis in early stage of severe acute pancreatitis]. AB - OBJECTIVE: To analyze the correlation between fluid equilibrium and oxygen index in patients at early stage (within 2 weeks) of severe acute pancreatitis (SAP), and to discuss the effects of fluid equilibrium after resuscitation on the prognosis. METHODS: A clinical study was conducted. Ninety-seven patients with SAP admitted into Shengjing Hospital of China Medical University directly or transferred into intensive care unit (ICU) in 24 hours after admission between March 2011 to October 2013 were studied. Finally, 65 patients were enrolled in statistical analysis, and those with termination of treatment prematurely were excluded. The patients received treatment protocol formulated by the same physician in ICU. Patients were divided into improved group and death group according to the outcome. The differences in fluid equilibrium on 1, 2, 3, 7, 14 days after admission of ICU between the two groups were compared. The correlation between fluid equilibrium and oxygen index was analyzed with curve fitting. RESULTS: Among 65 patients enrolled, 53 of them were improved after intensive care and were transferred into ordinary wards. However, 12 patients died in ICU. Patients in the improved group showed delayed positive fluid equilibrium, and some patients even showed negative fluid equilibrium. Patients in death group needed more fluid to achieve fluid equilibrium. There was a significant difference in the need of fluid to reach an equilibrium between improved group and death group [1 day: 1 814.5 (905.2, 2 152.8) mL vs. 3 891.0 (2 524.2, 5 714.5) mL, Z=-3.303, P=0.001; 2 days: 2 469.0 (1 456.0, 3 696.0) mL vs. 6 498.0 (4 617.8, 8 763.5) mL, Z=-4.431, P<0.001; 3 days: 3 234.0 (1 098.0, 4 295.5) mL vs. 9 533.5 (6 748.8, 10 689.0) mL, Z=-4.684, P<0.001; 7 days: 3 234.0 (1 033.0, 5 162.0) mL vs. 13 986.5 (8 045.8, 14 518.0) mL, Z=-4.718, P<0.001; 14 days: 3 234.0 (978.5, 4 924.0) mL vs. 13 436.5 (8 045.8, 14 518.0) mL, Z=-4.769, P<0.001]. There was no correlation between fluid equilibrium and oxygen index in improved patients within 3 days of ICU admission (R2 = 0.000, P=0.827), and it fit the logistic curve in a relatively low level after 3 days of ICU admission (R2 = 0.036, P<0.001). CONCLUSIONS: Early fluid resuscitation could help maintain hemodynamics stability in SAP patients. Those SAP patients who showed a negative equilibrium in early stage showed a better prognosis, and the fluid equilibrium and oxygen index in improved patients fit the logistic curve after 3 days of ICU admission. PMID- 25124909 TI - [Comparison of the performance of three prehospital trauma scores in evaluation of injury severity among Lushan earthquake victims]. AB - OBJECTIVE: To investigate the performance of revised trauma score (RTS), CRAMS score (circulation, respiration, abdomen, motor and speech) and prehospital index (PHI) on evaluation of injury severity in earthquake victims. METHODS: Data of victims admitted to West China Hospital of Sichuan University during the Lushan earthquake from April 20th, 2013, to April 27th were retrospectively analyzed. The clinical information at admission was recorded, and the injury severity score (ISS), RTS, CRAMS and PHI were calculated. The optimal cut-off values were looked for, the comparability between the three scores and ISS score were figured out by receiver operator characteristic curve (ROC curve), and the correlation between ISS and three scores was analyzed by linear regression analysis. RESULTS: There was a total of 263 victims included in the study. ISS >= 16 was found in 86 cases, and ISS<16 in 177 victims, and there were significant statistic differences in male ratio (67.4% vs. 50.8%, chi2 = 6.477, P=0.011), RTS score [7.55 (0.29) vs. 7.84 (0), U=6 825, P=0.013] and CRAMS scores [8 (1) vs. 9 (1), U=3 977, P=0.000] between two groups. It was showed by ROC curve analysis that the area under the ROC curve (AUC) of RTS, CRAMS and PHI was 0.547 (P=0.220), 0.734 (P=0.000) and 0.544 (P=0.250), and the Youden indexes of the three scores were 0.093, 0.443, and 0.119, respectively. Moreover, the best cut-off values of them were 4.9, 9.5 and 3.5. Linear regression analysis showed that RTS and CRAMS score showed negative correlation with ISS score (r1=-0.139, P1=0.024; r2=-0.413, P2=0.000), while PHI showed no relationship with it (r=0.071, P=0.250). CONCLUSIONS: Of these three scoring systems, CRAMS has the best correlation with ISS, and it can be used in the prompt assessment of trauma severity in earthquake victims. PMID- 25124910 TI - [Effect of Sheshang capsule on platelet function of rabbits bitten by Trimeresurus stejnegeri and its mechanism]. AB - OBJECTIVE: To investigate the effect of the Sheshang capsule on coagulation of the rabbits bitten by Trimeresurus stejnegeri and its mechanism. METHODS: The changes in platelet aggregation rate was observed after the establishment of rabbits model by subcutaneously injection with 0.75, 1.50, 2.25, and 3.00 mL/kg of Trimeresurus stejnegeri venom for 72 hours. Fifty New Zealand white rabbits were randomly divided into five groups, 10 rabbits in each group. Rabbit model was reproduced by subcutaneously injection with 0.75 mL/kg of Trimeresurus stejnegeri venom. The rabbits in sham group were injected with 0.75 mL/kg normal saline(NS). The rabbits were gavaged with 5, 10, 15 mL * kg-1 * d-1 of the Sheshang concoction to the low, intermediate and high dose groups respectively after 6 hours, and 10 mL * kg-1 * d-1 NS was fed in the sham group and model group. The platelet aggregation rate, platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) were determined after 1 week. RESULTS: (1) With the increase in the concentration of Trimeresurus stejnegeri venom, 1-min, 3-min, 5-min and maximum platelet aggregation rates showed a gradual declining trends. (2) Compared with the sham group, 5-min and maximum platelet aggregation rate in the model group were significantly decreased [35.5 (24.2, 42.5)% vs. 43.0 (38.2, 58.5)%, 39.5 (29.0, 45.0)% vs. 46.5 (39.2, 60.2)%, both P<0.05]. Compared with the model group, 5-min and maximum platelet aggregation rate in the intermediate dose group were significantly increased [44.0 (39.8, 45.0) % vs. 35.5 (24.2, 42.5) %, 45.5 (43.5, 46.2) % vs. 39.5 (29.0, 45.0) %, both P<0.05]. There was no significant difference in platelet aggregation rate among the other groups. Compared with the sham group, PLT count in model group was obviously reduced (410.3 +/- 155.3 * 109/L vs. 724.5 +/- 220.7 * 109/L, P<0.01), so as MPV and PCT done [MPV: 5.11 +/- 1.09 fl vs. 6.34 +/- 1.16 fl, P<0.01; PCT: 21.9 (18.6, 26.8) % vs. 34.8 (24.8, 45.4) %, P<0.05]. Compared with the model group, PLT and PCT in the low, intermediate and high dose groups were significantly increased [PLT: 702.4 +/- 166.3 * 109/L, 648.5 +/- 160.2 * 109/L, 789.3 +/- 86.2 * 109/L vs. 410.3 +/- 155.3 * 109/L, PCT: 38.8 (35.7, 42.9)%, 36.0 (29.8, 44.4)%, 43.1 (40.5, 48.8)% vs. 21.9 (18.6, 26.8)%, all P<0.01], and MPV in the intermediate dose group was significantly increased (6.26 +/- 1.05 fl vs. 5.11 +/- 1.09 fl, P<0.01). There was no significant difference in PDW among groups (P>0.05). Compared with the sham group, cAMP (47.57 +/- 12.76 nmol/L vs. 36.67 +/- 10.54 nmol/L) and PKA (14.68 +/- 5.80 MUg/L vs. 9.23 +/- 4.05 MUg/L) in the model group were significantly increased (both P<0.05). Compared with the model group, cAMP and PKA of each dose group were decreased, while cAMP in low dose group [(36.33 +/- 11.08) nmol/L] and PKA in the intermediate dose group [(10.21 +/- 5.31) MUg/L] were significant decreased (both P<0.05). CONCLUSIONS: In the range of experimental concentration (0-3 mL/kg), the higher the concentration, and the stronger the inhibition of platelet aggregation rate was. The Sheshang capsule can raise platelet aggregation rate and PLT, increase MPV and PCT, and act against inhibition of platelet aggregation effect of the venom, thus improve the haemostatic function of platelet. Sheshang capsule can be used to treat the coagulopathy induced by Trimeresurus stejnegeri venom through regulating cAMP/PKA pathways. PMID- 25124911 TI - [Effects of hypertonic sodium chloride hydroxyethyl starch solution on cerebral vasospasm following subarachnoid hemorrhage and its mechanism]. AB - OBJECTIVE: To investigate the protective effect and potential mechanisms of hypertonic sodium chloride hydroxyethyl starch solution (HSH) against the cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH). METHODS: Twenty four male Sprague-Dawley (SD) rats were randomly assigned to four groups according to the random number table, with 6 rats in each group. The SAH-CVS model was reproduced by injection of the blood twice through the cisterna magna. Rats in both model and HSH treatment groups received 8 mL/kg normal saline (NS) or HSH treatment everyday via caudal vein. Rats in sham group were injected with 1.5 mL/kg NS into cisterna magna followed by 8 mL/kg NS treatment. Rats in normal group received no treatment. Rats were sacrificed to harvest basilar artery after 7 days. The thickness of vessel wall and lumen area were measured using hematoxylin-eosin (HE) staining. The rate of apoptosis of vascular smooth muscle cell (VSMC) was assessed using flow cytometry. Caspase-3 activity was measured by a fluorometric assay. The expressions of Bax and Bcl-2 were determined by Western Blot. Intracellular reactive oxygen species (ROS) was detected by H2DCFDA. RESULTS: Compared with normal group, increased thickness of vessel wall (27.72 +/ 1.94 MUm vs. 18.30 +/- 1.10 MUm, P<0.05), decreased lumen area (26 115 +/- 1 991 MUm2 vs. 55 080 +/- 2 091 MUm2, P<0.05), and elevation of rate of apoptosis of VSMCs [(35.05 +/- 5.54) % vs. (5.93 +/- 1.53) %, P<0.05] were found in model group. Compared with model group, decreased thickness of vessel wall (22.55 +/- 1.50 MUm vs. 27.72 +/- 1.94 MUm, P<0.05), increase of lumen area (48 115 +/- 2 460 MUm2 vs. 26 115 +/- 1 991 MUm2, P<0.05), and depressed rate of apoptosis of VSMCs [(16.54 +/- 5.94) % vs. (35.05 +/- 5.54) %, P<0.05] were found in HSH treatment group. Caspase-3 activity, intracellular ROS level, Bax and Bcl-2 expressions in model group were (188.40 +/- 19.35)%, (163.50 +/- 17.02)%, (208.71 +/- 26.04)% and (44.52 +/- 9.61) % of those of normal group, and the differences of these parameters between model and normal groups were statistically significant (all P<0.05). Caspase-3 activity, intracellular ROS level, Bax and Bcl-2 expressions in HSH treatment group were (135.05 +/- 19.52)%, (119.44 +/- 11.50)%, (139.20 +/- 18.04)% and (85.35 +/- 13.12)% of those of normal group, respectively, and the differences of these parameters between HSH treatment and model groups were statistically significant (all P<0.05). The differences of all measurements between sham and normal groups were not statistically significant. CONCLUSIONS: The current results demonstrate that HSH attenuates the SAH-induced CVS, alleviates thickness of vessel wall, and increases lumen area via inhibition of VSMCs apoptosis. PMID- 25124912 TI - [The change in auditory evoked potentials of brainstem in patients with skull base fracture and hypoacusia]. PMID- 25124913 TI - [Diagnosis and treatment of a patient with serous Q-fever, a case report]. PMID- 25124914 TI - [Analysis of 2 cases of pulmonary embolism]. PMID- 25124915 TI - [Application of dexmedetomidine sedation in treatment of continuous state of asthma, a case report]. PMID- 25124916 TI - [Nuclear factor-KappaB pathway and acute lung injury in hemorrhagic shock]. PMID- 25124917 TI - [An experience of the clinical features and treatment patients of the acute snake bite around Shaanxi Guanzhong area]. PMID- 25124918 TI - [Glycocalyx and fluid management in patients with sepsis]. PMID- 25124919 TI - [Value of lung ultrasonography in the diagnosis of acute respiratory distress syndrome]. PMID- 25124920 TI - The independent association of plateletcrit with long-term outcomes in patients undergoing primary percutaneous coronary intervention. AB - PURPOSE: Platelets play a key role in the genesis of thrombosis. Plateletcrit (PCT) provides complete information on total platelet mass. The relationship between PCT values and long-term outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary angioplasty is not known. We sought to determine the effect of PCT values on the outcomes of primary angioplasty for STEMI. METHODS: Overall, 2572 consecutive STEMI patients (mean age, 56.6+/-11.8 years) undergoing primary percutaneous coronary intervention were enrolled retrospectively into the present study. Plateletcrit at admission was measured as part of the automated complete blood count. Patients were classified into 2 groups: high PCT (>0.237, n=852) and nonhigh PCT (<0.237, n=1720). Clinical characteristics and in-hospital and long-term (median, 21 months) outcomes of primary angioplasty were analyzed. RESULTS: A higher in hospital shock rate was observed among patients with high PCT values compared with those with nonhigh PCT values (6.5 vs 3.8%, respectively; P=.003). The long term cardiovascular prognosis was worse for patients with high PCT values (Kaplan Meier, log-rank test; P=.007). We used Cox proportional hazard models to examine the association between PCT and adverse clinical outcomes. High PCT values were also an independent predictor of cardiovascular mortality (hazard ratio, 1.85; 95% confidence interval, 1.061-3.22; P=.03). CONCLUSION: High PCT values on admission are independently associated with long-term adverse outcomes in patients with STEMI who undergo primary angioplasty. PMID- 25124922 TI - Thoracic pedicle classification determined by inner cortical width of pedicles on computed tomography images: its clinical significance for posterior vertebral column resection to treat rigid and severe spinal deformities-a retrospective review of cases. AB - BACKGROUND: Posterior vertebral column resection (PVCR) is an effective alternative for treating rigid and severe spinal deformities. Accurate placement of pedicle screws, especially apically, is crucial. As morphologic evaluations of thoracic pedicles have not provided objective criteria, we propose a thoracic pedicle classification for treating rigid and severe spinal deformities. METHODS: A consecutive series of 56 patients with severe and rigid spinal deformities who underwent PVCR at a single institution were reviewed retrospectively. Altogether, 1098 screws were inserted into thoracic pedicles at T2-T12. Based on the inner cortical width of the thoracic pedicles, the patients were divided into four groups: group 1 (0-1.0 mm), group 2 (1.1-2.0 mm), group 3 (2.1-3.0 mm), group 4 (>=3.1 mm). The proportion of screws accurately inserted in thoracic pedicles for each group was calculated. Statistical analysis was also performed regarding types of thoracic pedicles classified by Lenke et al. (SPINE 35:1836-1842, 2010) using a morphological method. RESULTS: There were statistically significant differences in the rates of screws inserted in thoracic pedicles between the groups (P < 0.008) except groups 3 and 4 (P > 0.008), which were then combined. The accuracies for the three new groups were 35.05%, 65.34%, and 88.32%, respectively, with statistically significant differences between the groups (P < 0.017). Rates of screws inserted in thoracic pedicles classified by Lenke et al. (SPINE 35:1836-1842, 2010) were 82.31%, 83.40%, 80.00%, and 30.28% for types A, B, C, and D, respectively. There was no statistically significant difference (P > 0.008) between these types except between type D and the other three types (P < 0.008). CONCLUSIONS: The inner cortical width of thoracic pedicles is the sole factor crucial for accurate placement of thoracic pedicle screws. We propose a computed tomography-based classification of the pedicle's inner cortical width: type I thoracic pedicle: absent channel, inner cortical width of 0-1 mm; type II: presence of a channel of which type IIa has an inner cortical width of 1.1-2.0 mm and type IIb a width of >=2.1 mm. The proposed classification can help surgeons predict whether screws can be inserted into the thoracic pedicle, thus guiding instrumentation when PVCR is performed. PMID- 25124921 TI - Glutathione peroxidase's reaction intermediate selenenic acid is stabilized by the protein microenvironment. AB - Selenenic acids are highly reactive intermediates of selenoproteins' enzymatic reactions. Knowledge of how the protein environment protects and stabilizes them is fundamental not only to descriptions of selenoproteins' reactivity but also potentially for proteomics and therapeutics. However, selenenic acids are considered particularly short-lived and are not yet identified in wild-type selenoproteins. Here, we report trapping the selenenic acid in glutathione peroxidase, an antioxidant enzyme that efficiently eliminates hydroperoxides. It has long been thought that selenium-containing glutathione peroxidases form a selenenic acid intermediate. However, this putative species has eluded detection. Here, we report its identification. The selenenic acid in bovine glutathione peroxidase 1 was chemically trapped using dimedone, an alkylating agent specific to sulfenic and selenenic acids. The alkylation of the catalytic selenocysteine was verified by electrospray ionization mass spectrometry. In the presence of glutathione, the selenocysteine was not alkylated because the selenenic acid condenses faster with glutathione than the alkylation reaction. In the absence of thiols, the selenenic acid was surprisingly long-lived with 95% of the protein still able to react with dimedone 10 min after hydrogen peroxide was removed, indicating that the protein environment stabilizes the selenenic acid by shielding it from reactive groups in the protein. After 30 min, the selenocysteine was no longer modified but became accessible once the protein was exposed to reducing agents. This suggests that the selenenic acid reacted with a protein's amide or amine to form a selenylamide bond. Such a modification may play a role in protecting glutathione peroxidase'' reactivity. PMID- 25124923 TI - Small metastasizing choroidal melanomas. AB - PURPOSE: Small choroidal melanomas have a better prognosis than large tumours. However, these small tumours can spread, often late in their course. The aim of the study was to analyse survival and tumour characteristics of six cases of late metastatic diseases after conservative treatment. METHODS: A retrospective study was conducted at the Croix-Rousse University Hospital of Lyon among 523 patients treated between 1991 and 2010 by proton beam therapy (508) or brachytherapy with 106 (Ru/Rh) (15) for uveal melanomas. We have selected patients with small choroidal melanoma (thickness<=3 mm and diameter<=9 mm) (59 patients), who have developed hepatic metastases (six of 59). RESULTS: At the time of diagnosis, median age was 57 years (range, 37-82 years). The mean tumour thickness was 2.9 mm (range 2.5-3 mm), and the mean diameter was 7 mm (5-8 mm). Orange pigment was observed in four cases, subretinal fluid was observed in two cases, and one tumour touched the optic disc. Five patients had proton beam therapy. One patient had beta brachytherapy (106 Ru/106 Rh). Average follow-up was 8.3 years (range 4.2-11.8 years). None of the six patients developed local tumour recurrence. The mean survival time after diagnosis of melanoma was 9.8 years (range, 4.9-14.6 years). The average time from treatment of primary tumour to detection of liver metastasis was 7 years (range 3.9-12 years). The mean survival time from the diagnosis of metastasis was 35.2 months (range 9-101 months). Small melanoma related death was 0% at 3 years, 1.7% at 5 years, 5.1% at 10 years and 10.2% at 15 years in our series. CONCLUSIONS: Despite a small tumoral size and an early and effective local treatment, six of 59 small choroidal melanomas have developed metastasis after local treatment. Small tumours represent a significant risk of metastasis. PMID- 25124924 TI - Prolyl isomerase Pin1 in cancer. AB - Proline-directed phosphorylation is a posttranslational modification that is instrumental in regulating signaling from the plasma membrane to the nucleus, and its dysregulation contributes to cancer development. Protein interacting with never in mitosis A1 (Pin1), which is overexpressed in many types of cancer, isomerizes specific phosphorylated Ser/Thr-Pro bonds in many substrate proteins, including glycolytic enzyme, protein kinases, protein phosphatases, methyltransferase, lipid kinase, ubiquitin E3 ligase, DNA endonuclease, RNA polymerase, and transcription activators and regulators. This Pin1-mediated isomerization alters the structures and activities of these proteins, thereby regulating cell metabolism, cell mobility, cell cycle progression, cell proliferation, cell survival, apoptosis and tumor development. PMID- 25124925 TI - Hydrogen peroxide primes heart regeneration with a derepression mechanism. AB - While the adult human heart has very limited regenerative potential, the adult zebrafish heart can fully regenerate after 20% ventricular resection. Although previous reports suggest that developmental signaling pathways such as FGF and PDGF are reused in adult heart regeneration, the underlying intracellular mechanisms remain largely unknown. Here we show that H2O2 acts as a novel epicardial and myocardial signal to prime the heart for regeneration in adult zebrafish. Live imaging of intact hearts revealed highly localized H2O2 (~30 MUM) production in the epicardium and adjacent compact myocardium at the resection site. Decreasing H2O2 formation with the Duox inhibitors diphenyleneiodonium (DPI) or apocynin, or scavenging H2O2 by catalase overexpression markedly impaired cardiac regeneration while exogenous H2O2 rescued the inhibitory effects of DPI on cardiac regeneration, indicating that H2O2 is an essential and sufficient signal in this process. Mechanistically, elevated H2O2 destabilized the redox-sensitive phosphatase Dusp6 and hence increased the phosphorylation of Erk1/2. The Dusp6 inhibitor BCI achieved similar pro-regenerative effects while transgenic overexpression of dusp6 impaired cardiac regeneration. H2O2 plays a dual role in recruiting immune cells and promoting heart regeneration through two relatively independent pathways. We conclude that H2O2 potentially generated from Duox/Nox2 promotes heart regeneration in zebrafish by unleashing MAP kinase signaling through a derepression mechanism involving Dusp6. PMID- 25124928 TI - Domestic incense burning and nasopharyngeal carcinoma: a case-control study in Hong Kong Chinese. AB - Incense burning is a powerful producer of carcinogens and has been considered as a risk factor for nasopharyngeal carcinoma (NPC). We conducted a case-control study and case-only analyses to investigate the effect of incense burning and its interaction with genetic background on NPC risk among Hong Kong Chinese. Between June 2010 and December 2012, we recruited 352 incident cases of NPC and 410 controls. We collected information on lifelong practice of domestic incense burning via interviews and genotyped 80 single nucleotide polymorphisms (SNPs) in DNA repair genes. We observed an increased NPC risk associated with daily burning in women [Adjusted OR = 2.49, 95% confidence interval (CI): 1.33, 4.66] but not in men. The adjusted OR for daily burning with poor ventilation was 2.08 (95% CI: 1.02, 4.24), while that with good ventilation was 1.35 (95% CI: 0.92, 1.98). Interactions between 2 SNPs (rs2074517 and rs4771436) and incense burning were significantly associated with NPC risk and tended to have a SNP exposure-response effect. Evidence for gene-environment interactions supported the knowledge that NPC is a multi-factorial disease resulting from the joint effects of environmental exposures and inherited susceptibility. PMID- 25124926 TI - Arginase I, polyamine, and prostaglandin E2 pathways suppress the inflammatory response and contribute to diffuse cutaneous leishmaniasis. AB - Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of tegumentary leishmaniasis. The molecular mechanisms underlying DCL pathogenesis remain unclear, and there is no efficient treatment available. This study investigated the systemic and in situ expression of the inflammatory response that might contribute to suppression in DCL. The plasma levels of arginase I, ornithine decarboxylase (ODC), transforming growth factor beta (TGF-beta), and prostaglandin E2 (PGE2) were higher in patients with DCL, compared with patients with localized cutaneous leishmaniasis (LCL) or with controls from an area of endemicity. In situ transcriptomic analyses reinforced the association between arginase I expression and enzymes involved in prostaglandin and polyamine synthesis. Immunohistochemistry confirmed that arginase I, ODC, and cyclooxygenase2 expression was higher in lesion biopsy specimens from patients with DCL than in those from patients with LCL. Inhibition of arginase I or ODC abrogates L. amazonensis replication in infected human macrophages. Our data implicate arginase I, ODC, PGE2, and TGF-beta in the failure to mount an efficient immune response and suggest perspectives in the development of new strategies for therapeutic intervention for patients with DCL. PMID- 25124927 TI - Characterization of drug-resistant influenza A(H7N9) variants isolated from an oseltamivir-treated patient in Taiwan. AB - BACKGROUND: Patients contracting influenza A(H7N9) infection often developed severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs) are the primary option for treatment, but information on drug-resistance markers for influenza A(H7N9) is limited. METHODS: Four NA variants of A/Taiwan/1/2013(H7N9) virus containing a single substitution (NA-E119V, NA-I222K, NA-I222R, or NA-R292K) recovered from an oseltamivir-treated patient were tested for NAI susceptibility in vitro; their replicative fitness was evaluated in cell culture, mice, and ferrets. RESULTS: NA-R292K led to highly reduced inhibition by oseltamivir and peramivir, while NA-E119V, NA-I222K, and NA-I222R caused reduced inhibition by oseltamivir. Mice infected with any virus showed severe clinical signs with high mortality rates. NA-I222K virus was the most virulent in mice, whereas virus lacking NA change (NA-WT) and NA-R292K virus seemed the least virulent. Sequence analysis suggests that PB2-S714N increased virulence of NA I222K virus in mice; NS1-K126R, alone or in combination with PB2-V227M, produced contrasting effects in NA-WT and NA-R292K viruses. In ferrets, all viruses replicated to high titers in the upper respiratory tract but produced only mild illness. NA-R292K virus, showed reduced replicative fitness in this animal model. CONCLUSIONS: Our data highlight challenges in assessment of the replicative fitness of H7N9 NA variants that emerged in NAI-treated patients. PMID- 25124930 TI - Role of sleep duration as a risk factor for Type 2 diabetes among adults of different ages in Japan: the Niigata Wellness Study. AB - AIM: To compare the role of short sleep duration as a risk factor for diabetes among adults of different ages. METHODS: The study enrolled 38987 Japanese individuals without diabetes, and the 8-year risk of developing diabetes attributable to different sleep durations (< 5.5 h, 5.5 to < 6.5 h, 6.5 to < 7.0 h, 7.0-7.5 h, > 7.5-8.0 h, or > 8.0 h) was assessed among individuals aged <= 45, 46-59 or >= 60 years. RESULTS: During the 8-year follow-up period, 2085 individuals developed diabetes. Overall, individuals with a short sleep duration of < 5.5 h or 5.5 to < 6.5 h had, respectively, a 1.53-fold (95% CI 1.19, 1.97) or 1.25-fold (95% CI 1.10, 1.42) increased risk of diabetes as compared with those who had 7.0-7.5 h of sleep. A sleep duration of < 5.5 h or 5.5 to < 6.5 h was predictive of the development of diabetes among individuals aged <= 45 years, but not among those aged >= 60 years. With increasing age, the effect of short sleep duration on the risk of diabetes was attenuated. CONCLUSIONS: Short sleep duration was predictive of diabetes among young or middle-aged Japanese adults but not among elderly individuals after age was considered. Managing habitual short sleep and the possible reasons for having such short sleep duration could be particularly important for young or middle-aged adults in the development of future diabetes. PMID- 25124933 TI - Diagnosis and treatment of dynamic collapse of the cricotracheal ligament in thoroughbred racehorses. AB - OBJECTIVE: To describe (1) diagnosis of dynamic collapse of the cricotracheal ligament in a group of horses and (2) treatment and outcome of affected horses. STUDY DESIGN: Retrospective case series. ANIMALS: Thoroughbred horses (n = 8). METHODS: Of 600 over ground dynamic endoscopic examinations performed, 8 Thoroughbred horses had cricotracheal ligament collapse (CTLC); 5 were 2 years old and in early training and 2 were mature horses in full work. CTLC was diagnosed if circumferential collapse of the cricotracheal ligament was identified during exercise. Seven horses had repeat endoscopic examination. Two horses unresponsive to conservative management were treated surgically. RESULTS: Multiple abnormalities of the upper portion of the respiratory tract were identified along with CTLC in all five 2-year-old horses and resolution of CTLC was observed after treatment for upper airway inflammation. No concurrent respiratory abnormality was identified in the 2 mature horses. Surgical reduction of the cricotracheal space and imbrication of the cricotracheal ligament of these 2 horses resulted in resolution of clinical signs of CTLC. CONCLUSIONS: CTLC is a rare cause of dynamic obstruction in Thoroughbred racehorses. Resolution may occur after adaptation to training and after inflammation of the respiratory tract is resolved, but for horses with persistent CTLC, surgical reduction of the cricotracheal space and imbrication of the cricotracheal ligament may result in resolution of clinical signs. PMID- 25124932 TI - Complete response of sunitinib therapy for renal cell cancer recurrence in the native kidney after renal transplantation: a case report. AB - BACKGROUND: No case report has yet shown that sunitinib therapy for the postoperative recurrence of renal cancer in a native kidney after renal transplantation can achieve complete response (CR). CASE PRESENTATION: A tumor was detected in the right native kidney of a 35-year-old Japanese male 10 years after renal transplantation. A tumor thrombus that reached the atrium was detected, which suggested cT3cN0M0. Because of the risk of perioperative complications, preoperative therapy with sunitinib was selected and 8 courses were administered. The size of the primary tumor was reduced by 33%, while that of the tumor thrombus was decreased by 39.5%. Right nephrectomy and removal of the tumor thrombus were then performed. Contrast-enhanced computed tomography (CT) four months after surgery suggested local relapse. Sunitinib was administered for 9 months, which led to complete response (CR). CONCLUSIONS: This study presented the case of sunitinib therapy for renal cancer in the native kidney after renal transplantation. The therapeutic efficacy and safety for such cases should be discussed. PMID- 25124929 TI - Functionalized nanoscale micelles with brain targeting ability and intercellular microenvironment biosensitivity for anti-intracranial infection applications. AB - Due to complication factors such as blood-brain barrier (BBB), integrating high efficiency of brain target ability with specific cargo releasing into one nanocarrier seems more important. A brain targeting nanoscale system is developed using dehydroascorbic acid (DHA) as targeting moiety. DHA has high affinity with GLUT1 on BBB. More importantly, the GLUT1 transportation of DHA represents a "one way" accumulative priority from blood into brain. The artificial micelles are fabricated by a disulfide linkage, forming a bio-responsive inner barrier, which can maintain micelles highly stable in circulation and shield the leakage of entrapped drug before reaching the targeting cells. The designed micelles can cross BBB and be further internalized by brain cells. Once within the cells, the drug release can be triggered by high intracellular level of glutathione (GSH). Itraconazole (ITZ) is selected as the model drug because of its poor brain permeability and low stability in blood. It demonstrates that the functionalized nanoscale micelles can achieve highly effective direct drug delivery to targeting site. Based on the markedly increased stability in blood circulation and improved brain delivery efficiency of ITZ, DHA-modified micelles show highly effective in anti-intracranial infection. Therefore, this smart nanodevice shows a promising application for the treatment of brain diseases. PMID- 25124931 TI - Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly, lymphedema, and chorioretinal dysplasia caused by KIF11 mutations. AB - IMPORTANCE: Retinal detachment with avascularity of the peripheral retina, typically associated with familial exudative vitreoretinopathy (FEVR), can result from mutations in KIF11, a gene recently identified to cause microcephaly, lymphedema, and chorioretinal dysplasia (MLCRD) as well as chorioretinal dysplasia, microcephaly, and mental retardation (CDMMR). Ophthalmologists should be aware of the range of presentations for mutations in KIF11 because the phenotypic distinction between FEVR and MLCRD/CDMMR portends management implications in patients with these conditions. OBJECTIVE: To identify gene mutations in patients who present with a FEVR phenotype and explore the spectrum of ocular and systemic abnormalities caused by KIF11 mutations in a cohort of patients with FEVR or microcephaly in conjunction with chorioretinopathy or FEVR. DESIGN, SETTING, AND PARTICIPANTS: Clinical data and DNA were collected from each participant between 1998 and 2013 from the clinical practices of ophthalmologists and clinical geneticists internationally. Twenty-eight FEVR probands with diagnoses made by the referring physician and without a known FEVR gene mutation, and 3 with microcephaly and chorioretinopathy, were included. At least 1 patient in each pedigree manifested 1 or more of the following: macular dragging, partial retinal detachment, falciform folds, or total retinal detachment. EXPOSURES: Whole-exome sequencing was conducted on affected members in multiplex pedigrees, and Sanger sequencing of the 22 exons of the KIF11 gene was performed on singletons. Clinical data and history were collected and reviewed. MAIN OUTCOMES AND MEASURES: Identification of mutations in KIF11. RESULTS: Four novel heterozygous KIF11 mutations and 1 previously published mutation were identified in probands with FEVR: p.A218Gfs*15, p.E470X, p.R221G, c.790-1G>T, and the previously described heterozygous p.R47X. Documentation of peripheral avascular areas on intravenous fluorescein angiography was possible in 2 probands with fibrovascular proliferation demonstrating phenotypic overlap with FEVR. CONCLUSIONS AND RELEVANCE: Mutations in KIF11 cause a broader spectrum of ocular disease than previously reported, including retinal detachment. The KIF11 gene likely plays a role in retinal vascular development and mutations in this gene can lead to clinical overlap with FEVR. Cases of FEVR should be carefully inspected for the presence of microcephaly as a marker for KIF11-related disease to enhance the accuracy of the prognosis and genetic counseling. PMID- 25124934 TI - Biofilms formed by the archaeon Haloferax volcanii exhibit cellular differentiation and social motility, and facilitate horizontal gene transfer. AB - BACKGROUND: Archaea share a similar microbial lifestyle with bacteria, and not surprisingly then, also exist within matrix-enclosed communities known as biofilms. Advances in biofilm biology have been made over decades for model bacterial species, and include characterizations of social behaviors and cellular differentiation during biofilm development. Like bacteria, archaea impact ecological and biogeochemical systems. However, the biology of archaeal biofilms is only now being explored. Here, we investigated the development, composition and dynamics of biofilms formed by the haloarchaeon Haloferax volcanii DS2. RESULTS: Biofilms were cultured in static liquid and visualized with fluorescent cell membrane dyes and by engineering cells to express green fluorescent protein (GFP). Analysis by confocal scanning laser microscopy showed that H. volcanii cells formed microcolonies within 24 h, which developed into larger clusters by 48 h and matured into flake-like towers often greater than 100 MUm in height after 7 days. To visualize the extracellular matrix, biofilms formed by GFP expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin T. Stains colocalized with larger cellular structures and indicated that the extracellular matrix may contain a combination of polysaccharides, extracellular DNA and amyloid protein. Following a switch to biofilm growth conditions, a sub population of cells differentiated into chains of long rods sometimes exceeding 25 MUm in length, compared to their planktonic disk-shaped morphology. Time-lapse photography of static liquid biofilms also revealed wave-like social motility. Finally, we quantified gene exchange between biofilm cells, and found that it was equivalent to the mating frequency of a classic filter-based experimental method. CONCLUSIONS: The developmental processes, functional properties and dynamics of H. volcanii biofilms provide insight on how haloarchaeal species might persist, interact and exchange DNA in natural communities. H. volcanii demonstrates some biofilm phenotypes similar to bacterial biofilms, but also has interesting phenotypes that may be unique to this organism or to this class of organisms, including changes in cellular morphology and an unusual form of social motility. Because H. volcanii has one of the most advanced genetic systems for any archaeon, the phenotypes reported here may promote the study of genetic and developmental processes in archaeal biofilms. PMID- 25124935 TI - Inverse associations of total and decaffeinated coffee with liver enzyme levels in National Health and Nutrition Examination Survey 1999-2010. AB - Coffee may have hepatoprotective effects and higher coffee consumption has been associated inversely with levels of liver enzymatic markers. However, it is unclear whether decaffeinated coffee is also associated with liver enzymes. The study population included 27,793 participants, age 20 or older, in the U.S. National Health and Nutrition Examination Survey (1999-2010). Coffee intake was evaluated by 24-hour dietary recall. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma glutamyl transaminase (GGT) were measured. We examined the relationship between coffee intake and enzymatic levels using weighted multiple variable logistic (abnormally elevated levels of enzymes) and linear regression (continuous enzymatic levels). Total coffee consumption was inversely associated with abnormal levels of all four liver enzymes and continuous levels of AST, ALP, and GGT. Compared to those reporting no coffee consumption, participants reporting >= 3 cups per day had an odds ratio (OR; 95% confidence interval [CI]) of 0.75 (0.63, 0.89), 0.82 (0.68, 0.98), 0.73 (0.55, 0.95), and 0.69 (0.57, 0.83) for abnormal levels of ALT, AST, ALP, and GGT, respectively. Similar inverse associations were found with decaffeinated coffee intake and abnormal levels of ALT (OR (>= 2 vs 0 cup/d): 0.62 [0.41, 0.94]), AST (0.74 [0.49, 1.11]), and GGT (0.70 [0.49-1.00]). CONCLUSION: Higher intakes of coffee, regardless of its caffeine content, were associated with lower levels of liver enzymes. PMID- 25124937 TI - High-level conversion of L-lysine into 5-aminovalerate that can be used for nylon 6,5 synthesis. AB - L-Lysine is a potential feedstock for the production of bio-based precursors for engineering plastics. In this study, we developed a microbial process for high level conversion of L-lysine into 5-aminovalerate (5AVA) that can be used as a monomer in nylon 6,5 synthesis. Recombinant Escherichia coli WL3110 strain expressing Pseudomonas putida delta-aminovaleramidase (DavA) and lysine 2 monooxygenase (DavB) was grown to high density in fed-batch culture and used as a whole cell catalyst. High-density E. coli WL3110 expressing DavAB, grown to an optical density at 600 nm (OD600 ) of 30, yielded 36.51 g/L 5AVA from 60 g/L L lysine in 24 h. Doubling the cell density of E. coli WL3110 improved the conversion yield to 47.96 g/L 5AVA from 60 g/L of L-lysine in 24 h. 5AVA production was further improved by doubling the L-lysine concentration from 60 to 120 g/L. The highest 5AVA titer (90.59 g/L; molar yield 0.942) was obtained from 120 g/L L-lysine by E. coli WL3110 cells grown to OD600 of 60. Finally, nylon 6,5 was synthesized by bulk polymerization of epsilon-caprolactam and delta valerolactam prepared from microbially synthesized 5AVA. The hybrid system demonstrated here has promising possibilities for application in the development of industrial bio-nylon production processes. PMID- 25124938 TI - Selective episiotomy vs. implementation of a non episiotomy protocol: a randomized clinical trial. AB - BACKGROUND: World Health Organization (WHO) recommends that the episiotomy rate should be around 10%, which is already a reality in many European countries. Currently the use of episiotomy should be restricted and physicians are encouraged to use their clinical judgment to decide when the procedure is necessary. There is no clinical evidence corroborating any indication of episiotomy, so until the present moment it is not yet known whether episiotomy is indeed necessary in any context of obstetric practice. OBJECTIVES: To compare maternal and perinatal outcomes in women undergoing a protocol of not performing episiotomy versus selective episiotomy. METHODS/DESIGN: An open label randomized clinical trial will be conducted including laboring women with term pregnancy, maximum dilation of 8 cm, live fetus in cephalic vertex presentation. Women with bleeding disorders of pregnancy, indication for caesarean section and those without capacity to consent and without legal guardians will be excluded. Primary outcomes will be frequency of episiotomy, delivery duration, frequency of spontaneous lacerations and perineal trauma, frequency of instrumental delivery, postpartum blood loss, need for perineal suturing, number of sutures, Apgar scores at one and five minutes, need for neonatal resuscitation and pH in cord blood. As secondary outcomes frequency complications of perineal suturing, postpartum perineal pain, maternal satisfaction, neonatal morbidity and admission newborn in NICU will be assessed. Women will be invited to participate and those who agree will sign the consent form and will be then assigned to a protocol of not conducting episiotomy (experimental group) or to a group that episiotomy is performed selectively according to the judgment of the provider of care delivery (control Group). The present study was approved by IMIP's Research Ethics Committee. TRIAL REGISTRATION: Clinical Trials Register under the number and was registered in ClinicalTrials.gov under the number NCT02178111. PMID- 25124936 TI - Antimicrobial and antibiofilm potential of biosurfactants isolated from lactobacilli against multi-drug-resistant pathogens. AB - BACKGROUND: Biosurfactants (BS) are amphiphilic compounds produced by microbes, either on the cell surface or secreted extracellularly. BS exhibit strong antimicrobial and anti-adhesive properties, making them good candidates for applications used to combat infections. In this study, our goal was to assess the in vitro antimicrobial, anti-adhesive and anti-biofilm abilities of BS produced by Lactobacillus jensenii and Lactobacillus rhamnosus against clinical Multidrug Resistant (MDR) strains of Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus (MRSA). Cell-bound BS from both L. jensenii and L. rhamnosus were extracted and isolated. The surface activities of crude BS samples were evaluated using an oil spreading assay. The antimicrobial, anti-adhesive and anti-biofilm activities of both BS against the above mentioned MDR pathogens were determined. RESULTS: Surface activities for both BS ranged from 6.25 to 25 mg/ml with clear zones observed between 7 and 11 cm. BS of both L. jensenii and L. rhamnosus showed antimicrobial activities against A. baumannii, E. coli and S. aureus at 25-50 mg/ml. Anti-adhesive and anti-biofilm activities were also observed for the aforementioned pathogens between 25 and 50 mg/ml. Finally, analysis by electron microscope indicated that the BS caused membrane damage for A. baumannii and pronounced cell wall damage in S. aureus. CONCLUSION: Our results indicate that BS isolated from two Lactobacilli strains has antibacterial properties against MDR strains of A. baumannii, E. coli and MRSA. Both BS also displayed anti-adhesive and anti-biofilm abilities against A. baumannii, E. coli and S. aureus. Together, these capabilities may open up possibilities for BS as an alternative therapeutic approach for the prevention and/or treatment of hospital-acquired infections. PMID- 25124939 TI - Lack of activity of betulin-based Oleogel-S10 in the treatment of actinic keratoses: a randomized, multicentre, placebo-controlled double-blind phase II trial. AB - BACKGROUND: Betulinic acid and other triterpenes have shown strong antitumour activity in vitro and in vivo. A triterpene extract of birch bark formed the base of Oleogel-S10 and allowed topical application. Two previous trials have shown efficacy and tolerability in the treatment of actinic keratoses (AKs) with betulin-based Oleogel-S10. OBJECTIVES: To confirm the efficacy and tolerability/safety of Oleogel-S10 in the treatment of AKs in a multicentre placebo-controlled study. METHODS: Patients (n = 165) were treated topically for 3 months in a four-arm parallel study design, randomly allocated to A (n = 53) Oleogel-S10 once daily, B (n = 51) Oleogel-S10 twice daily, or C (n = 25) or D (n = 28) placebo (petroleum jelly) once or twice daily, respectively. Clinical efficacy in this double-blind study was assessed by the investigators. Final and baseline biopsies were evaluated by central histopathology. RESULTS: Complete clearance of the target lesions was seen in 4% of patients in group A and 7% in group B, but not in the placebo groups. A clearance rate of > 75% was seen for 15% and 18% of patients in groups A and B, respectively, and for 13% in the placebo groups. These differences were not statistically significant. Histopathologically, 43.9% of patients showed a downgrading or clearance of the marker AK with no significant differences between the groups. Treatment with Oleogel-S10 was well tolerated. The tolerability as assessed by the investigator was mostly 'very good' (78.8%), followed by 'good' (18.2%) and only 1.2% assessed it as 'intolerable'. Patient-assessed tolerability was graded mostly 'very good' (56.4%) or 'good' (34.5%). CONCLUSIONS: Treatment with Oleogel-S10 was well tolerated during a treatment period of 3 months, yet was no better than placebo in terms of efficacy in the treatment of AKs. PMID- 25124940 TI - Sensitivity testing of trypanosome detection by PCR from whole blood samples using manual and automated DNA extraction methods. AB - Automated extraction of DNA for testing of laboratory samples is an attractive alternative to labour-intensive manual methods when higher throughput is required. However, it is important to maintain the maximum detection sensitivity possible to reduce the occurrence of type II errors (false negatives; failure to detect the target when it is present), especially in the biomedical field, where PCR is used for diagnosis. We used blood infected with known concentrations of Trypanosoma copemani to test the impact of analysis techniques on trypanosome detection sensitivity by PCR. We compared combinations of a manual and an automated DNA extraction method and two different PCR primer sets to investigate the impact of each on detection levels. Both extraction techniques and specificity of primer sets had a significant impact on detection sensitivity. Samples extracted using the same DNA extraction technique performed substantially differently for each of the separate primer sets. Type I errors (false positives; detection of the target when it is not present), produced by contaminants, were avoided with both extraction methods. This study highlights the importance of testing laboratory techniques with known samples to optimise accuracy of test results. PMID- 25124941 TI - A Fasciola hepatica-derived fatty acid binding protein induces protection against schistosomiasis caused by Schistosoma bovis using the adjuvant adaptation (ADAD) vaccination system. AB - Several efforts have been made to identify anti-schistosomiasis vaccine candidates and new vaccination systems. The fatty acid binding protein (FAPB) has been shown to induce a high level of protection in trematode infection. The adjuvant adaptation (ADAD) vaccination system was used in this study, including recombinant FABP, a natural immunomodulator and saponins. Mice immunised with the ADAD system were able to up-regulate proinflammatory cytokines (IL-1 and IL-6) and induce high IgG2a levels. Moreover, there was a significant reduction in worm burden, egg liver and hepatic lesion in vaccinated mice in two independent experiments involving Schistosoma bovis infected mice. The foregoing data shows that ADAD system using FABP provide a good alternative for triggering an effective immune response against animal schistosomiasis. PMID- 25124942 TI - Thermochromic luminescent nest-like silver thiolate cluster. AB - A novel discrete open high-nuclearity nest-like silver thiolate cluster complex, [Ag33 S3 (StBu)16 (CF3 COO)9 (NO3 )(CH3 CN)2 ](NO3 ) (1), has been isolated with nitrate and S(2-) anions acting as structure-directing templates. Its similar nest-like structure has been assembled into an extended layer [Ag31 S3 (StBu)16 (NO3 )9 ]n (2) by adjustment of auxiliary ligand. More interestingly, both complexes exhibit temperature-dependent luminescence of high sensitivity with a large fluorescence enhancement (12-fold for 1, 21-fold for 2), which can be easily recognized by the naked-eye (dramatic red-shift Delta=104 nm for 1, larger Delta=113 nm for 2 at 77 K compared to those at 298 K). The correlation between luminescent thermochromism and temperature-dependent variation of the coordination modes of template NO3 (-) anion, Ag???S and Ag???Ag distances are also elucidated through variable-temperature single-crystal X-ray crystal structure (VT-SCXRD) analyses. PMID- 25124943 TI - Pro re nata prescribing in a population receiving palliative care: a prospective consecutive case note review. AB - OBJECTIVES: To document pro re nata (PRN) prescribing practices and to identify patterns with respect to clinical characteristics and the medications prescribed. DESIGN: Prospective consecutive case note review. SETTING: Two interrelated consultative hospice and palliative care services in regional Victoria, Australia. PARTICIPANTS: Terminally ill inpatients and community-based individuals (N = 203) at the time of referral to a hospice or palliative care service. MEASUREMENTS: Number of medications that the referring physician prescribed on a PRN basis and on a regular basis for symptom control; comorbid disease, performance status, comorbidity burden, disease phase, and survival. RESULTS: Mean number of PRN medications prescribed was 3.0, with significantly higher rates in the last week of life (rate ratio (RR) = 1.30, 95% confidence interval (CI) = 1.07-1.59) and during the terminal phase of disease (RR = 1.36, 95% CI = 1.09-1.68). One-quarter of prescriptions were for medications that met the Beers consensus criteria for potentially inappropriate medication use in elderly persons. CONCLUSION: These descriptive baseline data are new. A mean of three different medications allows responsiveness to a variety of fluctuating symptoms, but there was a large range within the sample, indicating that some individuals and their caregivers have a high burden of administration-related decision-making. PMID- 25124944 TI - In vitro and in vivo anti-malarial activity of limonoids isolated from the residual seed biomass from Carapa guianensis (andiroba) oil production. AB - BACKGROUND: Carapa guianensis is a cultivable tree used by traditional health practitioners in the Amazon region to treat several diseases and particularly symptoms related to malaria. Abundant residual pressed seed material (RPSM) results as a by-product of carapa or andiroba oil production. The objective of this study was to evaluate the in vitro and in vivo anti-malarial activity and cytotoxicity of limonoids isolated from C. guaianensis RPSM. METHODS: 6alpha acetoxyepoxyazadiradione (1), andirobin (2), 6alpha-acetoxygedunin (3) and 7 deacetoxy-7-oxogedunin (4) (all isolated from RPSM using extraction and chromatography techniques) and 6alpha-hydroxy-deacetylgedunin (5) (prepared from 3) were evaluated using the micro test on the multi-drug-resistant Plasmodium falciparum K1 strain. The efficacy of limonoids 3 and 4 was then evaluated orally and subcutaneously in BALB/c mice infected with chloroquine-sensitive Plasmodium berghei NK65 strain in the 4-day suppressive test. RESULTS: In vitro, limonoids 1 5 exhibited median inhibition concentrations (IC50) of 20.7-5.0 MUM, respectively. In general, these limonoids were not toxic to normal cells (MRC-5 human fibroblasts). In vivo, 3 was more active than 4. At oral doses of 50 and 100 mg/kg/day, 3 suppressed parasitaemia versus untreated controls by 40 and 66%, respectively, evidencing a clear dose-response. CONCLUSION: 6alpha-acetoxygedunin is an abundant natural product present in C. guianensis residual seed materials that exhibits significant in vivo anti-malarial properties. PMID- 25124945 TI - Predictors in adolescence of ESRD in middle-aged men. AB - BACKGROUND: Identification of predictors of end-stage renal disease (ESRD) in adolescence could provide intervention targets and improve understanding of the cause. STUDY DESIGN: Register-based nested case-control study. SETTING & PARTICIPANTS: A cohort of all Swedish male residents born from 1952 through 1956 who attended mandatory military conscription examinations in late adolescence was used to identify 534 cases and 5,127 controls matched by birth year, county, and vital status. PREDICTOR: Erythrocyte sedimentation rate (ESR), proteinuria, blood pressure, and body mass index (BMI) in late adolescence. OUTCOMES: ESRD (defined here as dialysis therapy, kidney transplantation, surgical procedures creating long-term access for dialysis therapy, or chronic kidney disease stage 5) from 1985 through 2009. MEASUREMENTS: Physical working capacity and cognitive function score in late adolescence. Head of household's occupation and household crowding measured as person-per-room ratio from the 1960 census when participants were children. RESULTS: Proteinuria is associated notably with future ESRD, with an adjusted OR of 7.72 (95% CI, 3.94-15.14; P<0.001) for trace or positive dipstick findings. ESR has a dose-dependent association with ESRD with an adjusted OR of 2.07 (95%CI, 1.14-3.75; P=0.02) for ESR >15mm/h. Hypertension is associated strongly with future ESRD with an OR of 3.97 (95%CI, 2.08-7.59; P<0.001) for grade 2 hypertension and higher. Elevated BMI is associated statistically significantly with increased ESRD risk with an OR of 3.53 (95%CI, 2.04-6.11; P<0.001) for BMI >=30 compared with 18.5-<25kg/m(2). LIMITATIONS: The study was limited to men, with no initial estimation of glomerular filtration rate, and information on smoking was unavailable. CONCLUSIONS: ESR, proteinuria, BMI, and blood pressure in late adolescence are independent predictors of ESRD in middle aged men. This highlights the long natural history and importance of adopting a life-course approach when considering the cause of chronic kidney disease. PMID- 25124949 TI - Numbness of the forehead. PMID- 25124946 TI - Bottom-up impact on the cecidomyiid leaf galler and its parasitism in a tropical rainforest. AB - The relative importance of host-plant resources, natural enemies or their interactions in controlling the population of galling insects and their parasitism is poorly known for tropical gallers. In this study, we assessed the impacts of plant quality and density of host trees in regulating the densities of a galler species, the cecidomyiid leaf galler (Cecidomyiini sp. 1EJV) and its parasitoids and inquilines on Neoboutonia macrocalyx trees in Uganda. We manipulated the nutritional quality (or vigour) and the resource concentration with four levels each of fertilization and the group size of host tree. We then recorded the effects of these treatments on the growth rate and total leaf area of host plants, the density of gallers and their mortality by parasitoids and inquilines. Higher levels of fertilization and host density resulted in significantly higher total leaf area than did ambient nutrient levels, and lowest tree densities, respectively. Fertilization also caused significant change in the growth rate of leaf area. Both higher fertilization and host density caused higher density of gallers. Total leaf area was positively associated with galler density, but within galled replicates, the galled leaves were larger than the ungalled leaves. Although highest levels of fertilization and density of host trees caused significant change in the densities of parasitoids, the rate of parasitism did not change. However, tree-density manipulations increased the rate of inquilinism, but on a very low level. Our results demonstrate a trophic cascade in the tropical galler and its parasitoids as a response to bottom-up effects. PMID- 25124950 TI - Shimmering lights. PMID- 25124951 TI - Accelerometer-assessed physical activity and diabetic retinopathy in the United States. PMID- 25124952 TI - Effect of topical rebamipide on human conjunctival goblet cells. PMID- 25124953 TI - Tethered vitreous seeds following intravitreal melphalan for retinoblastoma. PMID- 25124954 TI - Follow-up on anterior chamber angiostrongyliasis. PMID- 25124955 TI - Vulnerable populations in the underuse of the US Health Care System by persons with diabetes mellitus and diabetic macular edema. PMID- 25124956 TI - Vulnerable populations in the underuse of the US Health Care System by persons with diabetes mellitus and diabetic macular edema-reply. PMID- 25124957 TI - Making sense of the evidence from the age-related eye disease study 2 randomized clinical trial. PMID- 25124958 TI - Making sense of the evidence from the age-related eye disease study 2 randomized clinical trial-reply. PMID- 25124960 TI - Melatonin heals the gut. PMID- 25124959 TI - Uric acid and clinical correlates of endothelial function in kidney transplant recipients. AB - Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores. METHODS: One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation (FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models. RESULTS: Uric acid was associated negatively with FMD% in an age- and gender adjusted model, while not in the multivariable model. No association was shown between uric acid and LnRHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated negatively with risk scores in the latter model only (p < 0.05). CONCLUSIONS: Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores. PMID- 25124961 TI - Introduction to special issue on microbiome influences on host immunity. PMID- 25124962 TI - MyD88 acts as an adaptor protein for inflammatory signalling induced by amyloid beta in macrophages. AB - Neuroinflammation is the complex innate immune response of neural tissue to control infection, and Toll-like receptors (TLRs), a major family of pattern recognition receptors (PRRs), have a key role in Alzheimer's disease (AD) progression. Innate immune cells, including macrophages, govern tailored inflammatory gene expression to regulate inflammatory responses, however the role of macrophages in AD pathogenesis is not clear. All TLRs, with the exception of TLR3, recruit the MyD88 adaptor, and evidence indicates a role for this adaptor in inflammatory and cognitive changes in mouse AD models, in addition to amyloid beta (Abeta)-induced inflammatory signalling at a cellular level. In the present study, we employed the use of Abeta to induce inflammatory signalling in immortalized macrophages. Data presented herein demonstrate that Abeta promoted the nuclear sequestration of NF-kappaB, and polarized macrophages to an M1 phenotype with downstream consequences on pro-inflammatory cytokine expression. Importantly, Abeta-induced TNF-alpha production was exacerbated in macrophages lacking MyD88, while MyD88 deficiency promoted NF-kappaB activation, enhanced M1 and M2 polarization, and compromised macrophage viability. We demonstrate that in the absence of MyD88, mitogen-activated protein kinase (MAPKs) act as upstream signalling intermediates targeted by Abeta in the cascade leading to TNF-alpha expression. Our findings offer a new role for MyD88 in cellular mechanisms underlying AD pathogenesis, indicating that MyD88 adaptors are key in regulating Abeta-induced inflammatory signalling in macrophages. PMID- 25124963 TI - Involvement of IL-6 and IL-1 receptor antagonist on intellectual disability. AB - Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with several neurodevelopmental disorders and their role in neuronal development is being investigated. To assess the possible influence of cytokines on the onset of intellectual disability (ID), we studied the polymorphisms of thirteen proinflammatory cytokine genes in 81 patients and 61 healthy controls. We demonstrated a significant association of interleukin-6 (IL-6) single nucleotide polymorphism (SNP) (-174 G/C and nt565 G/A), and interleukin-1 receptor antagonist (IL-1RA) (Mspa-I 11100) SNP with ID. Moreover, the IL-6 SNPs is an unfavorable genetic predisposition for females. The evaluation of circulating levels of IL-6 and IL-1RA showed that the serum concentrations of IL 6 were significantly higher in ID patients than in controls. These data suggest that functional cytokine gene polymorphisms may influence the development of ID. PMID- 25124964 TI - The growth of human scalp hair in females using visible red light laser and LED sources. AB - BACKGROUND AND OBJECTIVES: Low level laser (light) therapy (LLLT) has been demonstrated to promote hair growth in males. A double-blind randomized controlled trial was undertaken to define the safety and physiologic effects of LLLT on females with androgenic alopecia. METHODS: Forty-seven females (18-60 years old, Fitzpatrick I-IV, and Ludwig-Savin Baldness Scale I-2, I-3, I-4, II-1, II-2 baldness patterns) were recruited. A transition zone scalp site was selected; hairs were trimmed to 3 mm height; the area was tattooed and photographed. The active group received a "TOPHAT655" unit containing 21, 5 mW diode lasers (655 +/- 5 nm) and 30 LEDS (655 +/- 20 nm), in a bicycle-helmet like apparatus. The placebo group unit appeared identical, containing incandescent red lights. Patients treated at home every other day * 16 weeks (60 treatments, 67 J/cm(2) irradiance/25 minute treatment, 2.9 J dose), with follow up and photography at 16 weeks. A masked 2.85 cm(2) photographic area was evaluated by another blinded investigator. The primary endpoint was the percent increase in hair counts from baseline. RESULTS: Forty-two patients completed the study (24 active, 18 sham). No adverse events or side effects were reported. Baseline hair counts were 228.2 +/- 133.4 (N = 18) in the sham and 209.6 +/- 118.5 (N = 24) in the active group (P = 0.642). Post Treatment hair counts were 252.1 +/- 143.3 (N = 18) in the sham group and 309.9 +/- 166.6 (N = 24) in the active group (P = 0.235). The change in hair counts over baseline was 23.9 +/- 30.1 (N = 18) in the sham group and 100.3 +/- 53.4 (N = 24) in the active group (P < 0.0001). The percent hair increase over the duration of the study was 11.05 +/- 48.30 (N = 18) for the sham group and 48.07 +/- 17.61 (N = 24) for the active group (P < 0.001). This demonstrates a 37% increase in hair growth in the active treatment group as compared to the placebo group. CONCLUSIONS: LLLT of the scalp at 655 nm significantly improved hair counts in women with androgenetic alopecia at a rate similar to that observed in males using the same parameters. PMID- 25124965 TI - Using virtual human technology to provide immediate feedback about participants' use of demographic cues and knowledge of their cue use. AB - Demographic characteristics have been found to influence pain management decisions, but limited focus has been placed on participants' reactions to feedback about their use of sex, race, or age to make these decisions. The present study aimed to examine the effects of providing feedback about the use of demographic cues to participants making pain management decisions. Participants (N = 107) viewed 32 virtual human patients with standardized levels of pain and provided ratings for virtual humans' pain intensity and their treatment decisions. Real-time lens model idiographic analyses determined participants' decision policies based on cues used. Participants were subsequently informed about cue use and completed feedback questions. Frequency analyses were conducted on responses to these questions. Between 7.4 and 89.4% of participants indicated awareness of their use of demographic or pain expression cues. Of those individuals, 26.9 to 55.5% believed this awareness would change their future clinical decisions, and 66.6 to 75.9% endorsed that their attitudes affect their imagined clinical practice. Between 66.6 and 79.1% of participants who used cues reported willingness to complete an online tutorial about pain across demographic groups. This study was novel because it provided participants feedback about their cue use. Most participants who used cues indicated willingness to participate in an online intervention, suggesting this technology's utility for modifying biases. PERSPECTIVE: This is the first study to make individuals aware of whether a virtual human's sex, race, or age influences their decision making. Findings suggest that a majority of the individuals who were made aware of their use of demographic cues would be willing to participate in an online intervention. PMID- 25124966 TI - Suture granuloma mimicking a recurrent sacro-coccygeal pilonidal sinus after Limberg flap. AB - Sacro-coccygeal pilonidal sinus disease is classified as an asymptomatic, acutely abscess-forming or chronic subcutaneous inflammation in the sacro-coccygeal region featuring characteristic pits in the bottom cleft. Due to high rates of recurrence, two flap techniques have been established in the course of the past three decades. One of them is the Karydakis operation, the other option is a rotation flap named Limberg procedure. We report about a case of suture granuloma in the area of a Limberg flap after recurrent pilonidal sinus with extrusion of the suture material, thus mimicking recurrence. In case of recurrent pilonidal sinus following plastic coverage or primary closure, respectively, the differential diagnosis of suture granuloma should be considered. PMID- 25124968 TI - Predictive findings of allergic disease in fiberoptic nasolaryngoscopy. AB - OBJECTIVES/HYPOTHESIS: To determine whether findings on fiberoptic nasolaryngoscopy beyond the nasal cavity can aid in diagnosis of atopy. STUDY DESIGN: Case control analysis of patients undergoing fiberoptic nasolaryngoscopy and allergy testing at a single academic institution. METHODS: Patients who underwent flexible nasolaryngoscopy for either laryngeal or nasal symptoms and allergy testing by in vitro methods were divided into an atopic group and a nonatopic control group based on results of allergy testing. Three board certified otolaryngologists who were blinded to the atopic status and symptoms viewed 88 patient videos and filled out an 8-item endoscopic rating questionnaire for each. Correlation between rater scores, endoscopic findings, and atopic status was calculated using Randolph's multirater kappa values and Mann-Whitney test. RESULTS: Intrarater reliability was moderate to perfect for all physicians on all questions (kappa 0.545-1.0). Inter-rater reliability was slight to fair (kappa 0.143-0.399) for all questions and the overall impression of atopic disease. Abnormalities of the torus tubarius (P = .007) and increased nasopharyngeal secretions (P = .038) were predictive of atopic disease, whereas the presence of an adenoid (P = .08) and impression of atopic disease (P = .15) approached significance. All other endoscopic measures were not predictive of atopic status. CONCLUSIONS: Fiberoptic nasolaryngeal findings within the nasopharynx rather than the larynx are predictive of a positive atopic status. LEVEL OF EVIDENCE: 3b. PMID- 25124967 TI - The FGF-1-specific single-chain antibody scFv1C9 effectively inhibits breast cancer tumour growth and metastasis. AB - Immunotherapy mediated by recombinant antibodies is an effective therapeutic strategy for a variety of cancers. In a previous study, we demonstrated that the fibroblast growth factor 1 (FGF-1)-specific recombinant antibody scFv1C9 arrests the cell cycle at the G0/G1 transition by blocking the intracrine FGF-1 pathway in breast cancer cells. Here, we further show that the overexpression of scFv1C9 in MCF-7 and MDA-MB-231 breast cancer cells by lentiviral infection resulted in decreased tumourigenicity, tumour growth and lung metastasis through FGF-1 neutralization. We found that scFv1C9 resulted in the up-regulation of p21, which in turn inhibited the expression of CDK2 and blocked cell cycle progression. To explore the potential role of scFv1C9 in vivo, we delivered the gene into solid tumours by electroporation, which resulted in significant inhibition of tumour growth. In tumour tissue sections, immunohistochemical staining of the cellular proliferation marker Ki-67 and the microvessel marker CD31 showed a reduction in the proliferative index and microvessel density, respectively, upon expression of scFv1C9 compared with the appropriate controls. Thus, our data indicate a central role for scFv1C9 in blocking the intracrine pathway of FGF-1, therefore, scFv1C9 could be developed in an effective therapeutic for breast cancer. PMID- 25124969 TI - Dosage individualization in children: integration of pharmacometrics in clinical practice. AB - BACKGROUND: Children are in a continuous and dynamically changing state of growth and development. A thorough understanding of developmental pharmacokinetics (PK) and pharmacodynamics (PD) is required to optimize drug therapy in children. DATA SOURCES: Based on recent publications and the experience of our group, we present an outline on integrating pharmacometrics in pediatric clinical practice to develop evidence-based personalized pharmacotherapy. RESULTS: Antibiotics in septic neonates and immunosuppressants in pediatric transplant recipients are provided as proof-of-concept to demonstrate the utility of pharmacometrics in clinical practice. Dosage individualization based on developmental PK-PD model has potential benefits of improving the efficacy and safety of drug therapy in children. CONCLUSION: The pharmacometric technique should be better developed and used in clinical practice to personalize drug therapy in children in order to decrease variability of drug exposure and associated risks of overdose or underdose. PMID- 25124970 TI - The role of surfactant and non-invasive mechanical ventilation in early management of respiratory distress syndrome in premature infants. AB - BACKGROUND: Surfactant replacement therapy has been used for few decades for the treatment of respiratory distress syndrome (RDS) and has significantly improved morbidity and mortality in premature infants. Non-invasive respiratory support has recently emerged as a strategy in the early management of RDS. In this review, we discuss the different strategies of early management of RDS. DATA SOURCES: A literature search of PubMed database was conducted to review the subject. The quality of evidence of key clinical studies was graded according to a modified grading system of the international GRADE group. RESULTS: Continuous positive airway pressure (CPAP) with selective surfactant is a safe alternative to routine intubation, surfactant and mechanical ventilation in preterm infants with spontaneous breathing, and such an approach has been associated with decreased risk of death and bronchopulmonary dysplasia. There is a risk of pneumothorax when using a high pressure of CPAP (>=8 cm of H2O), a high partial pressure of carbon dioxide (PCO2 >75 mm of Hg), and a high fraction of inspired oxygen (FiO2 >0.6) as a threshold for intubation while on CPAP. CONCLUSION: Not all preterm infants need surfactant treatment, and non-invasive respiratory support is a safe and effective approach. PMID- 25124971 TI - Bilirubin nomograms for identification of neonatal hyperbilirubinemia in healthy term and late-preterm infants: a systematic review and meta-analysis. AB - BACKGROUND: Hyperbilirubinemia occurs in most healthy term and late-preterm infants, and must be monitored to identify those who might develop severe hyperbilirubinemia. Total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) nomograms have been developed and validated to identify neonatal hyperbilirubinemia. This study aimed to review previously published studies and compare the TcB nomograms with the TSB nomogram, and to determine if the former has the same predictive value for significant hyperbilirubinemia as TSB nomogram does. METHODS: A predefined search strategy and inclusion criteria were set up. We selected studies assessing the predictive ability of TSB/TcB nomograms to identify significant hyperbilirubinemia in healthy term and late-preterm infants. Two independent reviewers assessed the quality and extracted the data from the included studies. Meta-Disc 1.4 analysis software was used to calculate the pooled sensitivity, specificity, and positive likelihood ratio of TcB/TSB nomograms. A pooled summary of the receiver operating characteristic of the TcB/TSB nomograms was created. RESULTS: After screening 187 publications from electronic database searches and reference lists of eligible articles, we included 14 studies in the systematic review and meta-analysis. Eleven studies were of medium methodological quality. The remaining three studies were of low methodological quality. Seven studies evaluated the TcB nomograms, and seven studies assessed TSB nomograms. There were no differences between the predictive abilities of the TSB and TcB nomograms (the pooled area under curve was 0.819 vs. 0.817). CONCLUSIONS: This study showed that TcB nomograms had the same predictive value as TSB nomograms, both of which could be used to identify subsequent significant hyperbilirubinemia. But this result should be interpreted cautiously because some methodological limitations of these included studies were identified in this review. PMID- 25124973 TI - No relationship between mode of delivery and neonatal mortality and neurodevelopment in very low birth weight infants aged two years. AB - BACKGROUND: To compare neonatal mortality and neurodevelopmental outcomes at two years of age in very low birth weight infants (<=1500 g) born by cesarean with those by vaginal delivery. METHODS: In this retrospective, case-control study, we evaluated neonatal mortality, medical conditions and neurodevelopmental outcomes at two years of corrected age in 710 very low birth weight (VLBW) infants born between January 2005 and December 2010. Of the 710 infants, 351 were born by the cesarean and 359/710 by vaginal route. RESULTS: There were no significant differences in neonatal mortality between the cesarean delivery group and vaginal delivery group [56/351 (15.9%) vs. 71/359 (19.8%), P=0.20]. VLBW infants delivered by the cesarean procedure had a higher incidence of respiratory distress syndrome than those born by the vaginal route [221/351 (63.0%) vs. 178/359 (49.6%), P<0.001]. There were no differences in other neonatal morbidities, including intraventricular hemorrhage [126/351 (35.9%) vs. 134/359 (37.3%), P=0.69], bronchopulmonary dysplasia [39/351 (11%) vs. 31/359 (8.6%), P=0.38] and necrotising enterocolitis [40/351 (11.4%) vs. 32/359 (8.9%), P=0.32] between the two groups. The incidence of poor neurodevelopment after cesarean delivery was similar to that after vaginal delivery [105/351 (29.9) vs. 104/359 (29.0%), P=0.78]. CONCLUSIONS: In neither neurodevelopment nor neonatal mortality did cesarean birth offered significant advantages to VLBW infants. Moreover, the operation might be associated with an increased risk of respiratory distress syndrome for VLBW infants. The mode of delivery of VLBW infants should be largely based on obstetric indications and maternal considerations rather than perceived better outcomes for the neonate. PMID- 25124972 TI - QDPR gene mutation and clinical follow-up in Chinese patients with dihydropteridine reductase deficiency. AB - BACKGROUND: This study aimed to investigate the mutation spectrum of the QDPR gene, to determine the effect of mutations on dihydropteridine reductase (DHPR) structure/function, to discuss the potential genotypephenotype correlation, and to evaluate the clinical outcome of Chinese patients after treatment. METHODS: Nine DHPR-deficient patients were enrolled in this study and seven of them underwent neonatal screening. QDPR gene mutations were analyzed and confirmed by routine methods. The potential pathogenicity of missense variants was analyzed using Clustal X, PolyPhen program and Swiss-PDB Viewer 4.04_OSX software, respectively. The clinical outcomes of the patients were evaluated after long term treatment. RESULTS: In 10 mutations of the 9 patients, 4 were novel mutations (G20V, V86D, G130S and A175R), 4 were reported by us previously, and 2 known mutations were identified. R221X was a hotspot mutation (27.7%) in our patients. Eight missense mutations probably had damage to protein. Six patients in this series were treated with a good control of phenylalanine level. The height and weight of the patients were normal at the age of 4 months to 7.5 years. Four patients, who underwent a neonatal screening and were treated early, showed a normal mental development. In 2 patients diagnosed late, neurological symptoms were significantly improved. CONCLUSIONS: The mutation spectrum of the QDPR gene is different in the Chinese population. Most mutations are related to severe phenotype. The determination of DHPR activity should be performed in patients with hyperphenylalaninemia. DHPR-deficient patients who were treated below the age of 2 months may have a near normal mental development. PMID- 25124974 TI - Effect of pravastatin on endothelial dysfunction in children with medium to giant coronary aneurysms due to Kawasaki disease. AB - BACKGROUND: Ongoing low-grade inflammation and endothelial dysfunction persist in children with coronary lesions diagnosed with Kawasaki disease (KD). Statins, frequently used in the management of high cholesterol, have also shown to improve surrogate markers of inflammation and endothelial dysfunction. This study was undertaken to investigate the efficacy and safety of pravastatin in children with coronary artery aneurysms due to KD. METHODS: The study enrolled 14 healthy children and 13 male children, aged 2-10 years, with medium-to-giant coronary aneurysms for at least 12 months after the onset of KD. Pravastatin was given orally to the KD group at a dose of 5 mg/day for children under 5 and 10 mg/day for children older than 5 years. To determine the effects of pravastatin on endothelial function, high-frequency ultrasound was performed before the start of the study and 6 months after pravastatin therapy. The parameters measured were brachial artery flow-mediated dilation (FMD), non-flow mediated dilation (NMD), and carotid artery stiffness index (SI). High sensitive C-reactive protein (hs CRP) levels, the circulating endothelial progenitor cells (EPCs) number, and serum lipid profiles were also determined at baseline and after 6 months of pravastatin treatment. RESULTS: Before treatment, the KD group had significantly decreased FMD (P<0.05) and increased SI and hs-CRP levels (P<0.05) compared with controls. After 6 months of pravastatin therapy, FMD improved significantly compared to the baseline KD group (3.16+/-6.49 to 10.05+/-7.74, P<0.05), but remained significantly less than that in the control group with no significant changes in NMD and SI. There were significant decreases in markers of inflammation after treatment. The hs-CRP levels decreased significantly from 2.93+/-0.81 mmol/L to 2.14+/-0.82 mmol/L (P<0.05) and the serum apo-B and apo B/apo-A1 ratio were also reduced (P<0.05) in the KD group. However, the circulating EPC number was not significantly different between baseline and that following pravastatin treatment in the KD group and the control group (P>0.05). No significant complications were noted with paravastatin therapy. CONCLUSIONS: Pravastatin improves endothelial function and reduces low-grade chronic inflammation in patients with coronary aneurysms due to KD. Children with coronary aneurysms due to KD may benefit from statin therapy. PMID- 25124975 TI - Congenital duodenal obstruction in neonates: a decade's experience from one center. AB - BACKGROUND: Congenital duodenal obstruction (CDO) is one of the most common anomalies in newborns, and accounting for nearly half of all cases of neonatal intestinal obstruction. This study aimed to review our single-center experience in managing congenital duodenal obstruction while evaluate the outcomes. METHODS: We conducted a retrospective analysis of the records of all neonates dianogsed with congenital duodenal obstruction admitted to our center between January 2003 and December 2012. We analyzed demographic criteria, clinical manifestations, associated anomalies, radiologic findings, surgical methods, postoperative complications, and final outcomes. RESULTS: The study comprised 287 newborns (193 boys and 94 girls). Birth weight ranged from 950 g to 4850 g. Fifty-three patients were born prematurely between 28 and 36 weeks' gestation. Malrotation was diagnosed in 174 patients, annular pancreas in 66, duodenal web in 55, duodenal atresia or stenosis in 9, preduodenal portal vein in 2, and congenital band compression in 1. Twenty patients had various combinations of these conditions. Presenting symptoms included bilious vomiting, dehydration, and weight loss. X-rays of the upper abdomen demonstrated the presence of a typical double-bubble sign or air-fluid levels in 68.64% of patients, and confirmatory upper and/or lower gastrointestinal contrast studies were obtained in 64.11%. Multiple associated abnormalities were observed in 50.52% of the patients. Various surgical approaches were used, including Ladd's procedure, duodenoplasty, duodenoduodenostomy, duodenojejunostomy, or a combination of these. Seventeen patients died postoperatively and 14 required re-operation. CONCLUSIONS: Congenital duodenal obstruction is a complex entity with various etiologies and often includes multiple concomitant disorders. Timely diagnosis and aggressive surgery are key to improving prognosis. Care should be taken to address all of the causes of duodenal obstruction and/or associated alimentary tract anomalies during surgery. PMID- 25124976 TI - Somatic growth of lean children: the potential role of sleep. AB - BACKGROUND: Despite the current obesity pandemic, childhood malnutrition remains an urgent, public health concern. Similar to the obesity pandemic, childhood malnutrition is influenced by genetic and a number of social, environmental and biological factors. In this study, we investigated the association between sleep duration and somatic growth in lean children. METHODS: A stratified, randomly clustered sampling design was used to select fifth grade students from 10 primary schools in Shanghai. Based on a body mass index below the 15th percentile a subsample of 143 lean children aged 10-11 years old was defined. Sleep duration and other potential confounders were surveyed through parental or self-report questionnaires. Body measurements were collected and used to calculate the Z score of weight, height, body mass index as well as body fat percentage. RESULTS: Compared with children who slept <9 hours, those who slept for >=10 hours grew taller and gained more weight after adjusting for confounding factors. When children slept 9-10 hours, they had significantly higher Z score of weight and body mass index. CONCLUSIONS: Prolonged sleep not only benefits weight gain but also improves height in lean children. Our findings might provide important public health advice such that prolonged sleep may be an effective modifier of nutritional problems in childhood. PMID- 25124977 TI - Improved outcomes of transported neonates in Beijing: the impact of strategic changes in perinatal and regional neonatal transport network services. AB - BACKGROUND: Infants born outside perinatal centers may have compromised outcomes due to the transfer speed and efficiency to an appropriate tertiary center. This study aimed to evaluate the impact of regional coordinated changes in perinatal supports and retrieval services on the outcome of transported neonates in Beijing, China. METHODS: Information about transported newborns between phase 1 (July 1, 2004 to June 30, 2006) and phase 2 (July 1, 2007 to June 30, 2009) was collected. The strategic changes during phase 2 included standardized neonatal transport procedures, skilled attendants, a perinatal consulting service, and preferential admission of transported neonates to the intensive care unit of the tertiary care center. Data from phase 2 (after-strategic changes) were compared with those of phase 1 (the period of pre-strategic changes) after a 12-month washout period, especially regarding the reduction in mortality and selected morbidity. RESULTS: There was a large increase in the number of transported infants in phase 2 compared with phase 1 (2797 vs. 567 patients). The average monthly rate of increase of transported infants was 383.3% (from 24 infants per month to 116 infants per month). The mortality rate of transported neonates reduced significantly from phase 1 to phase 2 (5.11% vs. 2.82%; P=0.005), particularly for preterm infants (8.47% vs. 4.34%; P=0.006). In addition, transported neonates during phase 2 had significantly decreased morbidities. CONCLUSIONS: Regional coordinated strategies optimizing the perinatal services and transport of outborn sick and preterm infants to tertiary care centers improved survival outcomes considerably. These findings have vital implications for health outcomes and resource planning. PMID- 25124978 TI - Placental growth factor expression is reversed by antivascular endothelial growth factor therapy under hypoxic conditions. AB - BACKGROUND: Clinical trials have revealed that the antivascular endothelial growth factor (VEGF) therapies are effective in retinopathy of prematurity (ROP). But the low level of VEGF was necessary as a survival signal in healthy conditions, and endogenous placental growth factor (PIGF) is redundant for development. The purpose of this study was to elucidate the PIGF expression under hypoxia as well as the influence of anti-VEGF therapy on PIGF. METHODS: CoCl2 induced hypoxic human umbilical vein endothelial cells (HUVECs) were used for an in vitro study, and oxygen-induced retinopathy (OIR) mice models were used for an in vivo study. The expression patterns of PIGF under hypoxic conditions and the influence of anti-VEGF therapy on PIGF were evaluated by quantitative reverse transcription-polymerase chain reaction (RTPCR). The retinal avascular areas and neovascularization (NV) areas of anti-VEGF, anti-PIGF and combination treatments were calculated. Retina PIGF concentration was evaluated by ELISA after treatment. The vasoactive effects of exogenous PIGF on HUVECs were investigated by proliferation and migration studies. RESULTS: PIGF mRNA expression was reduced by hypoxia in OIR mice, in HUVECs under hypoxia and anti-VEGF treatment. However, PIGF expression was reversed by anti-VEGF therapy in the OIR model and in HUVECs under hypoxia. Exogenous PIGF significantly inhibited HUVECs proliferation and migration under normal conditions, but it stimulated cell proliferation and migration under hypoxia. Anti-PIGF treatment was effective for neovascular tufts in OIR mice (P<0.05). CONCLUSION: The finding that PIGF expression is iatrogenically up-regulated by anti-VEGF therapy provides a consideration to combine it with anti-PIGF therapy. PMID- 25124979 TI - Clinical characteristics and mutation analysis of three Chinese children with autosomal recessive polycystic kidney disease. AB - BACKGROUND: There are few studies on the genotypes and phenotypes of autosomal recessive polycystic kidney disease in Chinese patients. METHODS: PKHD1 mutations in three children were detected with PCR and direct sequencing, and their clinical data were retrospectively reviewed. RESULTS: All of the children had bilateral enlarged polycystic kidneys, congenital hepatic fibrosis and intrahepatic bile duct dilatation. One of three children had classical multiple small cysts throughout the kidneys, and the other two children had bilateral multiple renal cysts of various sizes. Two children had abnormally shaped livers, portal hypertension and splenomegaly. Two heterozygous mutations (p.T36M, and p.P137S) were detected in Patient 1 and two were detected in Patient 2 (p.L2658X and p.V836A). One heterozygous mutation (p.L1425R) was detected in Patient 3. CONCLUSIONS: The study shows that renal and liver phenotypes of the Chinese children varied. Five mutations were identified in the three children, three of which were novel mutations. PMID- 25124980 TI - A novel CLCN5 mutation in a Chinese boy with Dent's disease. AB - BACKGROUND: Dent's disease is a rare X-linked recessive hereditary disease caused by mutations in either the CLCN5 or OCRL1 genes. This disease is characterized by manifestations of proximal renal tubule dysfunction associated with low molecular weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure. METHODS: We report a Chinese boy with Dent's disease, clinically diagnosed by LMWP and hypercalciuria. Genetic analysis was made of the CLCN5 and OCRL1 genes. Related studies were also reviewed. RESULTS: A splice site mutation IVS6, +2T>C of the CLCN5 gene was revealed in this case, and it was not reported previously. CONCLUSIONS: Clinical and genetic analysis is valuable for the diagnosis of Dent's disease. A novel mutation in the CLCN5 gene was identified in our patient. PMID- 25124981 TI - GATA3 mutation in a family with hypoparathyroidism, deafness and renal dysplasia syndrome. AB - BACKGROUND: The hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by GATA3 gene mutation. We report here a case that both of a Chinese boy and his father had HDR syndrome which caused by a novel mutation of GATA3. METHODS: Polymerase chain reaction and DNA sequencing was performed to detect the exons of the GATA3 gene for mutation analysis. RESULTS: Sequence analysis of GATA3 revealed a heterozygous nonsense mutation in this family: a mutation of GATA3 at exon 2 (c.515C >A) that resulted in a premature stop at codon 172 (p.S172X) with a loss of two zinc finger domains. CONCLUSION: We identified a novel nonsense mutation which will expand the spectrum of HDR-associated GATA3 mutations. PMID- 25124982 TI - Impact of caffeine and coffee on our health. AB - Coffee is the most frequently consumed caffeine-containing beverage. The caffeine in coffee is a bioactive compound with stimulatory effects on the central nervous system and a positive effect on long-term memory. Although coffee consumption has been historically linked to adverse health effects, new research indicates that coffee consumption may be beneficial. Here we discuss the impact of coffee and caffeine on health and bring attention to the changing caffeine landscape that includes new caffeine-containing energy drinks and supplements, often targeting children and adolescents. PMID- 25124984 TI - Reconceptualising the doctor-patient relationship: recognising the role of trust in contemporary health care. AB - The conception of the doctor-patient relationship under Australian law has followed British common law tradition whereby the relationship is founded in a contractual exchange. By contrast, this article presents a rationale and framework for an alternative model-a "Trust Model"-for implementation into law to more accurately reflect the contemporary therapeutic dynamic. The framework has four elements: (i) an assumption that professional conflicts (actual or perceived) with patient safety, motivated by financial or personal interests, should be avoided; (ii) an onus on doctors to disclose these conflicts; (iii) a proposed mechanism to contend with instances where doctors choose not to disclose; and (iv) sanctions for non-compliance with the regime. PMID- 25124985 TI - Cytometric analysis of surface molecules of leucocytes and phagocytic activity of granulocytes and monocytes/macrophages in cows with pyometra. AB - Pyometra is a serious problem in dairy cow herds, causing large economic losses due to infertility. The development of pyometra depends mainly on the immunological status of the cow. The aim of the study was a comparative evaluation of selected indicators involving non-specific and specific immunity in cows with pyometra and in cows without inflammation of the uterus. The study was performed in 20 cows, which were divided into two groups: pyometra group and healthy group, each comprising 10 cows, based on the results of cytological and ultrasonographic tests. A flow cytometric analysis was performed for the surface molecules CD4, CD8, CD14, CD21, CD25 and CD4(+) CD25(+) on leucocytes, and the phagocytic activity was determined from granulocytes and monocytes/macrophages in the peripheral blood and uterine washings, respectively. It was demonstrated that the percentage of phagocytic granulocytes and monocytes/macrophages in both the peripheral blood and uterine washings was significantly lower in cows with pyometra compared with the healthy group (p < 0.001). Significantly (p <= 0.001) lower percentage of CD4(+) , CD14(+) , CD25(+) and CD4(+) CD25(+) phenotype leucocytes was also observed in the peripheral blood of cows from the pyometra group, along with a significantly higher (p < 0.001) percentage of CD8(+) and CD21(+) lymphocytes as compared to the healthy group. The results of work indicate that disfunction of cell immunity coexisting with pyometra may be caused by a bacterial infection and the presence of blocking agents (IL-10), released by the increasing number of CD8(+) lymphocytes what leads to the advanced inflammation of uterus. PMID- 25124986 TI - Oxygen reduction reaction in a droplet on graphite: direct evidence that the edge is more active than the basal plane. AB - Carbon-based metal-free electrocatalysts for the oxygen reduction reaction (ORR) in alkaline medium have been extensively investigated with the aim of replacing the commercially available, but precious platinum-based catalysts. For the proper design of carbon-based metal-free electrocatalysts for the ORR, it would be interesting to identify the active sites of the electrocatalyst. The ORR was now studied with an air-saturated electrolyte solution droplet (diameter ca. 15 MUm), which was deposited at a specified position either on the edge or on the basal plane of highly oriented pyrolytic graphite. Electrochemical measurements suggest that the edge carbon atoms are more active than the basal-plane ones for the ORR. This provides a direct way to identify the active sites of carbon materials for the ORR. Ball-milled graphite and carbon nanotubes with more exposed edges were also prepared and showed significantly enhanced ORR activity. DFT calculations elucidated the mechanism by which the charged edge carbon atoms result in the higher ORR activity. PMID- 25124983 TI - Questions and answers on the Belgian model of integral end-of-life care: experiment? Prototype? : "Eu-euthanasia": the close historical, and evidently synergistic, relationship between palliative care and euthanasia in Belgium: an interview with a doctor involved in the early development of both and two of his successors. AB - This article analyses domestic and foreign reactions to a 2008 report in the British Medical Journal on the complementary and, as argued, synergistic relationship between palliative care and euthanasia in Belgium. The earliest initiators of palliative care in Belgium in the late 1970s held the view that access to proper palliative care was a precondition for euthanasia to be acceptable and that euthanasia and palliative care could, and should, develop together. Advocates of euthanasia including author Jan Bernheim, independent from but together with British expatriates, were among the founders of what was probably the first palliative care service in Europe outside of the United Kingdom. In what has become known as the Belgian model of integral end-of-life care, euthanasia is an available option, also at the end of a palliative care pathway. This approach became the majority view among the wider Belgian public, palliative care workers, other health professionals, and legislators. The legal regulation of euthanasia in 2002 was preceded and followed by a considerable expansion of palliative care services. It is argued that this synergistic development was made possible by public confidence in the health care system and widespread progressive social attitudes that gave rise to a high level of community support for both palliative care and euthanasia. The Belgian model of so-called integral end-of-life care is continuing to evolve, with constant scrutiny of practice and improvements to procedures. It still exhibits several imperfections, for which some solutions are being developed. This article analyses this model by way of answers to a series of questions posed by Journal of Bioethical Inquiry consulting editor Michael Ashby to the Belgian authors. PMID- 25124987 TI - Smoking ban is upheld at Scotland's State Hospital despite patient's earlier victory. PMID- 25124988 TI - Identification of promoter polymorphisms in the cytochrome P450 CYP6AY1 linked with insecticide resistance in the brown planthopper, Nilaparvata lugens. AB - Imidacloprid resistance in the brown planthopper, Nilaparvata lugens, is primarily the result of the over-expression of cytochrome P450 monooxygenases. Here, a field-collected strain of N. lugens was shown to be highly resistant to both imidacloprid and buprofezin. Insecticide exposure and quantitative real-time PCR revealed that its resistance was mainly associated with a cytochrome P450 gene, CYP6AY1. CYP6AY1 is known to metabolize imidacloprid but its effect on buprofezin is unclear. In the 5'-untranslated region of CYP6AY1, a novel alternative splicing was detected. After a 1990-bp promoter region was cloned, its basal luciferase activity was assessed. Furthermore, genotyping studies identified 12 variations in the promoter region that discriminated between the field-collected and control strain. Finally, survival bioassays revealed a single nucleotide polymorphism and an insertion-deletion polymorphism linked to buprofezin and imidacloprid resistance. Mutagenesis of these sites enhanced the promoter activity of CYP6AY1. These results suggest that promoter polymorphisms may affect P450-mediated multiple insecticide resistance of pests. PMID- 25124989 TI - Breaking the trade-off between thermal and electrical conductivities in the thermoelectric material of an artificially tilted multilayer. AB - Breaking the trade-off between thermoelectric (TE) parameters has long been demanded in order to highly enhance its performance. Here, we report the 'trade off-free' interdependence between thermal conductivity (kappa) and resistivity (rho) in a TE/metal tilted multilayer and significant enhancement of TE power generation based on the off-diagonal thermoelectric (ODTE) effect, which generates transverse electrical current in response to vertical thermal current. rho and kappa can be simultaneously decreased by setting charge flow along more electrically conductive layer and thermal flow across less-thermally conductive perpendicular direction by decreasing the tilting angle. Moreover, introducing porosity in the metal layer enables to decrease in kappa without changing rho, because the macroscopic rho and kappa of the tilted multilayer is respectively governed by the properties of the TE material and the metal with large dissimilarity. The obtained results reveal new strategies for developing trade off-free TE materials, which will stimulate practical use of TE conversion for waste-heat recovery. PMID- 25124990 TI - Spatial and temporal analysis of land cover changes and water quality in the Lake Issaqueena watershed, South Carolina. AB - Monitoring changes in land cover and the subsequent environmental responses are essential for water quality assessment, natural resource planning, management, and policies. Over the last 75 years, the Lake Issaqueena watershed has experienced a drastic shift in land use. This study was conducted to examine the changes in land cover and the implied changes in land use that have occurred and their environmental, water quality impacts. Aerial photography of the watershed (1951, 1956, 1968, 1977, 1989, 1999, 2005, 2006, and 2009) was analyzed and classified using the geographic information system (GIS) software. Seven land cover classes were defined: evergreen, deciduous, bare ground, pasture/grassland, cultivated, and residential/other development. Water quality data, including sampling depth, water temperature, dissolved oxygen content, fecal coliform levels, inorganic nitrogen concentrations, and turbidity, were obtained from the South Carolina (SC) Department of Health and Environmental Control (SCDHEC) for two stations and analyzed for trends as they relate to land cover change. From 1951 to 2009, the watershed experienced an increase of tree cover and bare ground (+17.4 % evergreen, +62.3 % deciduous, +9.8 % bare ground) and a decrease of pasture/grassland and cultivated land (-42.6 % pasture/grassland and -57.1 % cultivated). From 2005 to 2009, there was an increase of 21.5 % in residential/other development. Sampling depth ranged from 0.1 to 0.3 m. Water temperature fluctuated corresponding to changing air temperatures, and dissolved oxygen content fluctuated as a factor of water temperature. Inorganic nitrogen content was higher from December to April possibly due to application of fertilizers prior to the growing season. Turbidity and fecal coliform bacteria levels remained relatively the same from 1962 to 2005, but a slight decline in pH can be observed at both stations. Prior to 1938, the area consisted of single crop cotton farms; after 1938, the farms were abandoned, leaving large bare areas with highly eroded soil. Starting in 1938, Clemson reforested almost 30 % of the watershed. Currently, three fourths of the watershed is forestland, with a limited coverage of small farms and residential developments. Monitoring water quality is essential in maintaining adequate freshwater supply. Water quality monitoring focuses mainly on the collection of field data, but current water quality conditions depend on the cumulative impacts of land cover change over time. PMID- 25124991 TI - The role of subscapularis muscle denervation in the pathogenesis of shoulder internal rotation contracture after neonatal brachial plexus palsy: a study in a rat model. AB - We assessed the role of subscapularis muscle denervation in the development of shoulder internal rotation contracture in neonatal brachial plexus injury. Seventeen newborn rats underwent selective denervation of the subscapular muscle. The rats were evaluated at weekly intervals to measure passive shoulder external rotation. After 4 weeks, the animals were euthanized. The subscapularis thickness was measured using 7.2T MRI axial images. The subscapularis muscle was then studied grossly, and its mass was registered. The fiber area and the area of fibrosis were measured using collagen-I inmunostained muscle sections. Significant progressive decrease in passive shoulder external rotation was noted with a mean loss of 58 degrees at four weeks. A significant decrease in thickness and mass of the subscapularis muscles in the involved shoulders was also found with a mean loss of 69%. Subscapularis muscle fiber size decreased significantly, while the area of fibrosis remained unchanged. Our study shows that subscapularis denervation, per se, could explain shoulder contracture after neonatal brachial plexus injury, though its relevance compared to other pathogenic factors needs further investigation. PMID- 25124992 TI - Indocyanine green and fluorescence lymphangiography for sentinel lymph node identification in cutaneous melanoma. AB - BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy has become the standard method of determining regional lymph node involvement in cutaneous melanoma. Although traditionally performed via injection of radioisotope tracers and blue dyes, fluorescent lymphangiography with indocyanine green (ICG) is an attractive alternative. METHODS: Fifty two consecutive patients with cutaneous melanoma of the trunk or extremities underwent SLNB. Preoperative lymphoscintigraphy was performed with technetium-99m sulfur colloid (TSC). Peritumoral intradermal injection of isosulfan blue (ISB) and ICG was then performed. Successful identification of a sentinel lymph node via each modality was then assessed. RESULTS: A total of 77 lymph nodes were identified from the 52 patients (range 1-3). The majority of melanomas were extremity-based, superficial spreading type, and had SLN localized to the axilla. There were no complications related to IcG administration. Rates of SLN detection were 96.2% for TSC, 59.6% for ISB, and 88.5% for IcG (P < 0.05 for ICG vs ISB). On univariate logistic regression analysis, no factors were found to be associated with failure of ICG. CONCLUSIONS: Fluorescent lymphangiography using ICG is an effective method of SLN identification in patients with cutaneous melanoma of the trunk and extremities. When ICG and TSC are used in combination, ISB offers no additional advantage and may be safely omitted. PMID- 25124993 TI - The use of decision trees and naive Bayes algorithms and trace element patterns for controlling the authenticity of free-range-pastured hens' eggs. AB - This article aims to evaluate 2 machine learning algorithms, decision trees and naive Bayes (NB), for egg classification (free-range eggs compared with battery eggs). The database used for the study consisted of 15 chemical elements (As, Ba, Cd, Co, Cs, Cu, Fe, Mg, Mn, Mo, Pb, Se, Sr, V, and Zn) determined in 52 eggs samples (20 free-range and 32 battery eggs) by inductively coupled plasma mass spectrometry. Our results demonstrated that decision trees and NB associated with the mineral contents of eggs provide a high level of accuracy (above 80% and 90%, respectively) for classification between free-range and battery eggs and can be used as an alternative method for adulteration evaluation. PMID- 25124994 TI - Further evidence of the importance of RIT1 in Noonan syndrome. AB - Noonan syndrome (NS) is an autosomal dominant disorder consisting of short stature, short and/or webbed neck, distinctive facial features, cardiac abnormalities, cryptorchidism, and coagulation defects. NS exhibits genetic heterogeneity, associated with mutated genes that participate in RAS-mitogen activated protein kinase signal transduction. Recently, a new gene (RIT1) was discovered as the causative gene in 17 of 180 Japanese individuals who were negative for the previously known genes for NS and were studied using exome sequencing (four patients), followed by Sanger sequencing (13 patients). The present study used the same technique in 70 Brazilian patients with NS and identified six with RIT1 missense mutations. Thus, we confirm that RIT1 is responsible for approximately 10% of the patients negative for mutations in the previously known genes. The phenotype includes a high frequency of high birth weight, relative macrocephaly, left ventricular hypertrophy, and ectodermal findings, such as curly hair, hyperpigmentation, and wrinkled palms and soles. Short stature and pectus deformity were less frequent. The majority of patients with a RIT1 mutation did not show apparent intellectual disability. Because of the relatively high frequency of mutations in RIT1 among patients with NS and its occurrence in different populations, we suggest that it should be added to the list of genes included in panels for the molecular diagnosis of NS through targeted next-generation sequencing. PMID- 25124995 TI - Increased expression of cystatin C and transforming growth factor beta-1 in calcific aortic valves. PMID- 25124996 TI - The impact of anatomical remodeling of the left atrium and pulmonary vein on the recurrence of paroxysmal atrial fibrillation after catheter ablation. PMID- 25124997 TI - YOUng Football Italian amateur players Remote electrocardiogram Screening with Telemedicine (YOU FIRST) study: preliminary results. PMID- 25124999 TI - Variability of right ventricular angiography in arrhythmogenic right ventricular cardiomyopathy. PMID- 25124998 TI - Circulating miR-323-3p and miR-652: candidate markers for the presence and progression of acute coronary syndromes. AB - BACKGROUND: The prognostic utility of circulating plasma microRNA in patients with acute coronary syndromes (ACS) has been proposed but not yet demonstrated. We set out to investigate circulating microRNA levels in patients incurring recent ACS and examined associations with neurohormones, cardiac structure and function, and survival over 5 years of follow-up. METHODS: An initial screen of 375 microRNAs was performed in 35 ACS patients and 16 healthy controls. Candidates identified from the initial screen (miR-323-3p, miR-652, miR-27b, miR 103 and miR-208a) were validated in a further cohort of 200 patients at baseline (~ 30 days post-ACS) and at 4 and 12 months post-ACS, and compared with 100 controls. RESULTS: In the validation cohort, significantly higher levels in patients were replicated for miR-323-3p, miR-652 and miR-27b (10-fold, 2.3-fold and 2.3-fold, respectively, adjusted p<0.05). Lower levels of miR-103 were not replicated and miR-208a was undetectable. From baseline to 4 months post admission, miR-323-3p and miR-652 remained elevated in patients compared to controls (adjusted p<0.01), with no further change in levels between 4 and 12 months; whereas miR-27b fell to control levels by 4 months. Baseline levels of miR-652 in the lowest tertile were significantly associated with readmission for heart failure (log-rank p<0.001). In combination with NT-proBNP and LVEF, miR-652 significantly improved risk stratification (p<0.001). CONCLUSIONS: Our study identifies miR-652 as a novel candidate biomarker for post-ACS prognosis beyond existing biomarkers of LVEF and NT-proBNP. Moreover circulating miR-323-3p was markedly elevated in patients for at least a year post-ACS and may be a stable biomarker for ACS. PMID- 25125000 TI - Strenuous exercise and the heart: are we not seeing the wood for the trees? PMID- 25125002 TI - Gender differences in quality of life after PCI attenuate after a 10 year follow up. PMID- 25125001 TI - Reduced functionality in everyday activities of patients with self-reported heart failure hospitalization--population-based study results. AB - AIM: To assess daily functioning and geriatric conditions of older subjects suffering from heart failure (HF) as compared to the general population. METHODS AND RESULTS: The data were collected as part of the nationwide PolSenior project (2007-2011). Of 4979 individuals (age range 65-104 years), data on self-reported HF hospitalization were available for 4795 subjects (96%). Geriatric assessment (GA) included functional status (ADL, Activities of Daily Living and IADL, Instrumental ADL scales), cognitive function, mood disorders, sensory organ impairment, falls and comorbidity. Mean age +/- SD of the study population was 73.8 +/- 6.5 years; 62% were female. The proportion of subjects with HF hospitalizations increased from 8% in subjects aged 65-69 years up to 13% in the age group of 85-89 years, and decreased in nonagenarians (11%). Subjects with the HF hospitalization were older, used more drugs, and were characterized by a higher prevalence of comorbid conditions, mood disorders, hearing impairment and functional limitations. In logistic regression, HF hospitalization increased the age-sex adjusted risk of disability by 40%, both in ADL and IADL. After adjustment to other clinical and geriatric conditions, HF hospitalization remained an independent predictor of disability in both ADL (OR=1.36, 95%CI: 1.00 1.84) and IADL (OR=1.40, 95%CI: 1.01-1.93). CONCLUSIONS: Older people who reported HF admissions had a higher number of comorbidities and geriatric conditions: mood disorders, hearing impairment and functional limitations. Besides, in our study, HF hospitalization independently and significantly increased the risk of limitations in IADL and ADL. Therefore, further studies are needed to evaluate the benefits of GA in patients with HF. PMID- 25125003 TI - Is acute respiratory failure requiring mechanical ventilation associated with development of takotsubo cardiomyopathy in the critical care setting? PMID- 25125004 TI - Androgen attenuates cardiac fibroblasts activations through modulations of transforming growth factor-beta and angiotensin II signaling. AB - BACKGROUND: Androgen deficiency produces heart failure, which can be ameliorated by testosterone supplementation. Cardiac fibrosis plays a critical role in the pathophysiology of heart failure. This study aimed to evaluate whether testosterone can attenuate cardiac fibroblast activity through modulating transforming growth factor (TGF)-beta and angiotensin (Ang) II signaling. METHODS: Migration, proliferation, myofibroblast differentiation, collagen production, and transcription signaling were evaluated in adult male rat (weighing 300-350 g) cardiac fibroblasts with and without incubation with testosterone (10nM) and co-administration of TGF-beta1 (10 ng/ml) or Ang II (100 nM) by cell migration analysis, proliferation assay, soluble collagen measurement, zymographic analysis, immunofluorescence microscopy, real-time PCR and Western blot. RESULTS: Compared to those without testosterone, testosterone treated fibroblasts exhibited less collagen production. Testosterone-treated fibroblasts also had less migration, proliferation, myofibroblast differentiation, and collagen production in the presence of TGF-beta1, or had less collagen production with Ang II. Testosterone-treated fibroblasts had decreased phosphorylated Akt, mammalian target of rapamycin, and 4E binding protein-1 irrespective of TGF-beta1 treatment and had increased matrix metalloproteinase (MMP)-2 in the presence of TGF-beta1 treatment, and had decreased phosphorylated P38 and Smad 2/3 levels in the presence of Ang II. Cardiac fibroblasts with and without testosterone had similar mRNA and protein expressions of total Akt and total Smad 2/3 irrespective of TGF-beta1 or Ang II treatment. CONCLUSION: Physiological level of testosterone attenuated Akt and Smad 2/3 phosphorylation mediated by TGF-beta1 and angiotensin II respectively, which can result in decreased cardiac fibroblast activation and potentially contribute to beneficial effects in heart failure. PMID- 25125005 TI - Secondary prevention of sudden cardiac death in a 65 year untreated ALCAPA patient. PMID- 25125006 TI - Left ventricular or Bi-ventricular assist device? How dobutamine stress echocardiography can untie the dilemma of right ventricular dysfunction. PMID- 25125007 TI - Prognostic significance of mitral regurgitation in long-term all-cause mortality in patients aged >= 80 years with acute coronary syndrome. AB - BACKGROUND: Mitral regurgitation (MR) has been shown to be associated with a poor prognosis in the patients with acute myocardial infarction, whether or not percutaneous coronary intervention (PCI) is employed. However, the long-term prognostic significance of MR in octogenarian patients with acute coronary syndrome (ACS) remains unknown. We sought to determine the impact of MR on long term all-cause mortality and to further reveal whether PCI could influence the prognosis in octogenarian MR patients with ACS. METHODS: In this study, we included a total of 353 consecutive hospitalized patients, aged >= 80 years, with ACS during the period of 5-year follow-up. Association between MR and long-term all-cause mortality was analyzed both in a overall cohort and in a matched cohort developed from a propensity score analysis. RESULTS: MR was independently associated with long-term all-cause mortality in the overall and matched cohorts (hazard ratio (HR) 1.58, 95% CI 1.01-2.47, P=0.043; HR 1.90, 95% CI 1.15-3.13, P=0.013). In the subgroup treated with PCI, MR also exhibited higher long-term all-cause mortality, PCI remained an independent determinant of improving long term survival rate by reducing the mortality by 15.1% in ACS patients with MR aged >= 80 years. CONCLUSIONS: Our study demonstrates that MR is independently associated with long-term all-cause mortality, and PCI is an independent determinant for improving the long-term survival rate in the octogenarian ACS patients with MR. PMID- 25125008 TI - Relationship between fractional flow reserve and residual plaque volume and clinical outcomes after optimal drug-eluting stent implantation: insight from intravascular ultrasound volumetric analysis. AB - BACKGROUND: The underlying cause of FFR reduction and prognostic impact of FFR after optimal DES implantation remain unknown. The study aims were to use intravascular ultrasound (IVUS) to investigate the mechanism responsible for reduced fractional flow reserve (FFR) after optimal drug-eluting stent (DES) implantation and to evaluate FFR effect on clinical outcomes after optimal percutaneous coronary intervention with DES. METHODS: Ninety-seven patients treated with optimal DES implantation under IVUS and pullback FFR guidance were followed clinically (median 17.8 months). Post-stenting IVUS examination and pullback FFR recording were performed, and angiographic and IVUS parameters associated with reduced FFR were evaluated. The composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction, stent thrombosis, and target vessel revascularization, was analyzed. RESULTS: Regression analysis showed inverse correlations between post-stent FFR and residual plaque volume index (r=-0.40, p<0.01) and residual percent plaque volume (r=-0.68, p<0.01) in IVUS but no correlation of minimal lesion diameter with quantitative coronary angiography (r=0.07, p=0.50) or IVUS-derived minimal stent area (r=0.02, p=0.84). MACE was observed in 10 patients (10.3%), and FFR after optimal stenting was significantly lower in this group (0.86 +/- 0.04 vs 0.91 +/- 0.04, p<0.01). The optimal FFR threshold for predicting MACE was 0.90, identified by the receiver operating characteristic curve. CONCLUSIONS: Reduced FFR after optimal DES implantation was associated with residual plaque volume identified by IVUS and future adverse cardiac events. PMID- 25125009 TI - Neoatherosclerosis--a cause of late stent thrombosis? PMID- 25125010 TI - Postconditioning or preconditioning, which should be promoted in the protection of ischemic reperfusion injury? PMID- 25125011 TI - Reply: Comments on hypertonic saline with furosemide for the treatment of acute congestive heart failure: a systematic review and meta-analysis. PMID- 25125012 TI - Edentulism associates with poor cardiovascular health. Results from the Atahualpa Project. PMID- 25125013 TI - Switching from ticagrelor to prasugrel: a warning. PMID- 25125014 TI - Cerebral microemboli and neurocognitive change after carotid artery stenting with different embolic protection devices. AB - OBJECTIVES: Proximal cerebral protection devices have been developed as an alternative to filter protection devices for reducing neurological complications during carotid artery stenting (CAS). The aim of the present study was to evaluate the frequency of silent cerebral embolism after CAS using different cerebral embolic protection devices and the impact of silent cerebral embolism on neurocognitive function. METHODS: One hundred consecutive patients who underwent CAS were enrolled. The patients were randomized to either proximal balloon occlusion or filter protection. Neurocognitive tests were performed before and six months after CAS. Cerebral embolisms were evaluated with diffusion-weighted magnetic resonance imaging (DW-MRI). RESULTS: The number and volume of new ischemic lesions found with DW-MRI were higher in the filter protection group than in the proximal balloon occlusion group. According to our definition, nine (21%) patients in the balloon occlusion group and 16 (36%) patients in the filter protection group showed neurocognitive decline, and ten (23%) patients in the balloon occlusion group and four (9%) patients in the filter protection group showed neurocognitive improvement (NS). Regarding the group of patients with new cerebral ischemic lesions on DW-MRI, neurocognitive decline occurred in 14 (31%) of 45 patients with DW-MRI lesions and 11 (26%) of 43 patients without DW-MRI lesions (NS). CONCLUSION: Neurocognitive outcome after CAS is unpredictable; both neurocognitive decline and improvement can occur. In this study, the proximal balloon occlusion system significantly decreased cerebral microemboli during CAS compared to filter protection. Cerebral microembolism was not found to be associated with neurocognitive decline. PMID- 25125015 TI - Incidence and clinical characteristics of takotsubo cardiomyopathy post aneurysmal subarachnoid hemorrhage. PMID- 25125016 TI - Depression among cardiovascular patients living in a Middle Eastern country- preliminary findings from a cross-sectional survey. PMID- 25125017 TI - Glucagon-like peptide-1 levels on admission for acute myocardial infarction with or without acute hyperglycemia. PMID- 25125018 TI - Low plasma renin level is associated with the occurrence of angiographic radial artery spasm in patients undergoing transradial coronary procedures. PMID- 25125019 TI - Validation of a risk scoring model for prediction of acute cardiac complications in chest pain patients presenting to the Emergency Department. PMID- 25125020 TI - Chronic obstructive pulmonary disease and hypertrophic obstructive cardiomyopathy: two antagonistic obstructions. PMID- 25125021 TI - Inappropriate implantable cardioverter-defibrillator shocks and signal jammers: first report of a new interference. PMID- 25125022 TI - Quantifying subtle changes in cardiovascular mechanics in acromegaly: a Doppler myocardial imaging study. AB - AIM OF THE STUDY: To describe morphological and functional cardiovascular changes in acromegaly (ACM) patients, as well as to investigate the ability of Doppler based myocardial deformation imaging (DMI) to characterize subtle dysfunction in ACM. METHODS: 69 patients (pts) with ACM (mean age 47 +/- 10 years, 27 men) and 31 controls (mean age 43 +/- 16 years, matched for age and gender) were recruited. Standard echocardiography and DMI data were obtained for all patients. Peak systolic longitudinal strain values (S) were determined for the left and right ventricles. Radial S was measured at the level of the mid inferolateral segment. Using a high-resolution echo-tracking system, the main indices of arterial stiffness were measured. RESULTS: Of the ACM subjects, 57 had active disease (group A), and 12 controlled ACM (group B). All pts with ACM presented structural changes: a higher LV indexed mass (112 +/- 36, 118 +/- 23 vs 74 +/- 18 g/m(2), p < 0.001) and a higher relative wall thickness (0.45 +/- 0.09, 0.50 +/- 0.07 vs 0.40 +/- 0.07, p = 0.003) compared to controls. Also, ACM pts had functional changes: reduced LV ejection fraction (57 +/- 5, 55 +/- 5 vs 64 +/- 4%, p < 0.001) and altered diastolic function (E/A 1.0 +/- 0.4, 1.1 +/- 0.1 vs 1.3 +/- 0.3, p = 0.005) compared to controls. Both longitudinal and radial LV S values were lower in ACM compared to controls: -16.5 +/- 3.5, -16.8 +/- 4.3 vs 21.5 +/- 3.8%, p < 0.001 for longitudinal and 38.3 +/- 12.3, 35.6 +/- 11.8 vs 52.2 +/- 11.7%, p = 0.002 for radial strain. CONCLUSIONS: ACM pts present LV concentric hypertrophy and LV systolic and diastolic dysfunction, even in controlled disease. Altered global LV systolic function appears to be due both to longitudinal and radial dysfunction. PMID- 25125023 TI - A review of the effects of Nigella sativa L. and its constituent, thymoquinone, in metabolic syndrome. AB - BACKGROUND: Metabolic syndrome is an important risk factor for cardiovascular disease (CVD) occurrence and mortality. CVDs are leading cause of death worldwide. Recently, there has been an increasing interest in the use of herbal medicines with more efficiency and minimal undesirable effects than chemical drugs for a variety of disorders including CVD. Nigella sativa and its active constituent, thymoquinone, have been documented to exhibit antidiabetic, antiobesity, hypotensive and hypolipidemic properties. AIM: In this review, we discussed the most relevant articles to find out the role of N. sativa in different components of metabolic syndrome and CVD risk factors including high blood pressure, obesity, dyslipidemia and high blood glucose. CONCLUSIONS: This review suggests a potential role of N. sativa and TQ in the management of metabolic syndrome, however more studies should be conducted to evaluate their effectiveness. PMID- 25125024 TI - Psychosocial, behavioural, pedagogical, and nutritional proposals about how to encourage eating a healthy breakfast. AB - BACKGROUND: Even if more and more evidences have highlighted the importance of breakfast in the growth and development of children, from 10 to 30% of US and European children and adolescents regularly skip breakfast. Thus, there is still a lot to be done before breakfast becomes a daily habit. The aim of this paper is to try and understand how it is possible to overcome the real or imaginary difficulties associated with skipping breakfast by psychosocial, behavioural, pedagogical and nutritional proposals. DISCUSSION: Schools are the best context where perform healthy interventions because it is here that children learn about the importance of good health at an age when the school still plays a major role in their education. Some school interventions, based on solid theories as the Self Determination Theory and the Behaviour Analysis, have been implemented in the last years to promote health behaviour such as intake of fruit and vegetables and physical activities. Cognitive behaviour therapy is the most closely monitored type of treatment/cure for obesity in randomised controlled trials. Moreover some associations such as the National Association of Food Science Specialists have drawn an own method to encourage food education at school and promote the importance of prevention. These projects could be used as starting point to perform interventions focus on breakfast. SUMMARY: Increase the consumption of breakfast between children is very important. Efforts should be done to drawn new school projects based on scientific-evidences. PMID- 25125026 TI - Glial Asthenia and Functional Paralysis: A New Perspective on Neurodegeneration and Alzheimer's Disease. AB - Neuroglia are represented by several population of cells heterogeneous in structure and function that provide for the homeostasis of the brain and the spinal cord. Neuroglial cells are also central for neuroprotection and defence of the central nervous system against exo- and endogenous insults. At the early stages of neurodegenerative diseases including Alzheimer's disease neuroglial cells become asthenic and lose some of their homeostatic, neuroprotective, and defensive capabilities. Astroglial reactivity, for example, correlates with preservation of cognitive function in patients with mild cognitive impairment and prodromal Alzheimer's disease. Here, we overview the experimental data indicating glial paralysis in neurodegeneration and argue that loss of glial function is fundamental for defining the progression of neurodegenerative diseases. PMID- 25125025 TI - Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations. AB - Drug-drug interactions (DDIs) occur when a patient's response to the drug is modified by administration or co-exposure to another drug. The main cytochrome P450 (CYP) enzyme, CYP3A4, is implicated in the metabolism of almost all of the tyrosine kinase inhibitors (TKIs). Therefore, there is a substantial potential for interaction between TKIs and other drugs that modulate the activity of this metabolic pathway. Cancer patients are susceptible to DDIs as they receive many medications, either for supportive care or for treatment of toxicity. Differences in DDI outcomes are generally negligible because of the wide therapeutic window of common drugs. However for anticancer agents, serious clinical consequences may occur from small changes in drug metabolism and pharmacokinetics. Therefore, the objective of this review is to highlight the current understanding of DDIs among TKIs, with a focus on metabolism, as well as to identify challenges in the prediction of DDIs and provide recommendations. PMID- 25125027 TI - The spatiotemporal segregation of GAD forms defines distinct GABA signaling functions in the developing mouse olfactory system and provides novel insights into the origin and migration of GnRH neurons. AB - Gamma-aminobutyric acid (GABA) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 coexpressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually nonoverlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia In contrast GAD67 is expressed in a subregion of the nonsensory epithelium/vomeronasal organ epithelium containing the putative Gonadotropin releasing hormone (GnRH) progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and postmigratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock out embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools. PMID- 25125028 TI - A dual-task design of corrosion-controlling and osteo-compatible hexamethylenediaminetetrakis- (methylene phosphonic acid) (HDTMPA) coating on magnesium for biodegradable bone implants application. AB - Magnesium as well as its alloys appears increasingly as a revolutionary bio-metal for biodegradable implants application but the biggest challenges exist in its too fast bio-corrosion/degradation. Both corrosion-controllable and bio compatible Mg-based bio-metal is highly desirable in clinic. In present work, hexamethylenediaminetetrakis (methylenephosphonic acid) [HDTMPA, (H2 O3 P-CH2 )2 N-(CH2 )6 -N-(CH2 -PO3 H2 )2 ], as a natural and bioactive organic substance, was covalently immobilized and chelating-deposited onto Mg surface by means of chemical conversion process and dip-coating method, to fullfill dual-task performance of corrosion-protective and osteo-compatible functionalities. The chemical grafting of HDTMPA molecules, by participation of functional groups on pretreated Mg surface, ensured a firmly anchored base layer, and then sub sequential chelating reactions of HDTMPA molecules guaranteed a homogenous and dense HDTMPA coating deposition on Mg substrate. Electrochemical corrosion and immersion degradation results reveal that the HDTMPA coated Mg provides a significantly better controlled bio-corrosion/degradation behavior in phosphate buffer saline solution as compared with untreated Mg from perspective of clinic requirement. Moreover, the HDTMPA coated Mg exhibits osteo-compatible in that it induces not only bioactivity of bone-like apatite precipitation but also promotes osteoblast cells adhesion and proliferation. Our well-controlled biodegradable and biocompatible HDTMPA modified Mg might bode well for next generation bone implant application. PMID- 25125029 TI - Functionalized fullerene (C60) as a potential nanomediator in the fabrication of highly sensitive biosensors. AB - Designing a biosensor for versatile biomedical applications is a sophisticated task and how dedicatedly functionalized fullerene (C60) can perform on this stage is a challenge for today and tomorrow's nanoscience and nanotechnology. Since the invention of biosensor, many ideas and methods have been invested to upgrade the functionality of biosensors. Due to special physicochemical characteristics, the novel carbon material "fullerene" adds a new dimension to the construction of highly sensitive biosensors. The prominent aspects of fullerene explain its outstanding performance in biosensing devices as a mediator, e.g. fullerene in organic solvents exhibits five stages of reversible oxidation/reduction, and hence fullerene can work either as an electrophile or nucleophile. Fullerene is stable and its spherical structure produces an angle strain which allows it to undergo characteristic reactions of addition to double bonds (hybridization which turns from sp(2) to sp(3)). Research activities are being conducted worldwide to invent a variety of methods of fullerene functionalization with a purpose of incorporating it effectively in biosensor devices. The different types of functionalization methods include modification of fullerene into water soluble derivatives and conjugation with enzymes and/or other biomolecules, e.g. urease, glucose oxidase, hemoglobin, myoglobin (Mb), conjugation with metals e.g. gold (Au), chitosan (CS), ferrocene (Fc), etc. to enhance the sensitivity of biosensors. The state-of-the-art research on fullerene functionalization and its application in sensor devices has proven that fullerene can be implemented successfully in preparing biosensors to detect glucose level in blood serum, urea level in urine solution, hemoglobin, immunoglobulin, glutathione in real sample for pathological purpose, to identify doping abuse, to analyze pharmaceutical preparation and even to detect cancer and tumor cells at an earlier stage. Employing fullerene-metal matrix for the detection of tumor and cancer cells is also possible by the inclusion of fullerene in single-walled carbon nanotubes (SWCNTs) known as peapods as well as in double-walled carbon nanotubes (DWCNTs), to augment the effectiveness of biosensors. This review discusses various approaches that have been reported for functionalizing fullerene (C60) derivatives and their application in different types of biosensor fabrication. PMID- 25125031 TI - [A rare cause of cyanosis in a pre-term infant]. PMID- 25125030 TI - [Thrombopenia and the nature of the microorganism in infected critically ill children]. AB - BACKGROUND: Thrombopenia is correlated with sepsis and mortality in pediatric intensive care units. The purpose of this study was to find an association between thrombopenia and the microorganism type to guide the choice of empiric antibiotic therapy in infected critically ill children. MATERIALS AND METHODS: We conducted a prospective descriptive study, including all newborns, infants, and children admitted to a pediatric surgical intensive care unit from 1st January to 31st December 2009. We identified patients who developed an infection and/or thrombopenia (platelet count less than 100,000/mm(3)) during hospitalization. RESULTS: One hundred ninety-seven patients were included (57 newborns, 41 infants, 99 children). Ninety patients developed 100 infectious episodes during the study period. Of the 57 newborns enrolled in the study, 31 (54%) developed 37 infections. Seventy-six microorganisms (55 Gram-negative bacilli [GNB], 17 Gram positive cocci, two Gram-negative cocci, two fungal pathogens) were identified during 65 infectious episodes in 55 patients. Thirty-four episodes of thrombopenia were observed in 30 patients. Thrombopenia was observed only in infected patients (P<0.001). Thrombopenia was associated with infections caused by GNB (26/28 vs 20/37, P=0.001) and by Klebsiella (16/28 vs 6/37, P=0.001) and may be associated with infections caused by GNB producing extended-spectrum beta lactamases (P=0.07). Gram-positive cocci infections were correlated to the non occurrence of thrombopenia (P=0.02). Postoperative peritonitis was also significantly associated with thrombopenia (P=0.03). The mortality rate in our patients was 12.7% (22.8% in neonates). There was an association between thrombopenia and death in univariate analysis (11/25 vs 19/172, P<0.001). Multivariate logistic regression analysis did not confirm thrombopenia as an independent predictive factor of mortality in children. CONCLUSION: Because of the relatively high proportion of resistant GNB, an empiric antibiotic therapy combining a carbapenem and an aminoglycoside may be indicated in infected critically ill children developing thrombopenia. PMID- 25125032 TI - [Efficacy and safety of intravenous immunoglobulins in the management of neonatal hyperbilirubinemia due to ABO incompatibility: a meta-analysis]. AB - OBJECTIVES: ABO fetomaternal red blood cell incompatibility (ABO FMI) induces an immune hemolysis after fetal transfer of hemolyzing maternal anti-A or anti-B. ABO hemolytic disease (ABO HD) remains the most frequent cause of severe and early jaundice in newborns. High levels of unconjugated hyperbilirubinemia may induce acute and chronic neurological complications. Severe hyperbilirubinemia can be prevented by first-line phototherapy (PT) treatment, but exchange transfusion (ET) is required if treatment is not effective, even if ET is linked with high hemodynamic, infectious, gastrointestinal, and/or biological morbidity. Intravenous human polyclonal immunoglobulins (IVIg) have been proposed in concomitant use with PT in order to avoid the requirement for ET in ABO FMI. METHODS: Electronic databases of all published clinical trials in neonatal hyperbilirubinemia due to ABO incompatibility were systematically queried for randomized controlled clinical trials comparing PT alone to PT associated with IVIg based on the requirement for ET. Duration of PT and adverse events were optional criteria. A meta-analysis of the selected data was performed on six selected trials out of 28 found. RESULTS: IVIg doses ranged from 0.5 to 1.5 g/Kg in one to three administrations. Requirement for ET was lower in the IgIV+PT group, with a relative risk of 0.27 [CI 95% 0.17-0.42; P<0.00001], expressed as a number needed to treat of five neonates to avoid one ET. The mean duration of PT was 4 days in the PT group and association of PT with IVIg significantly reduced the duration of PT treatment by 0.84 days. The tolerance of the IVIg and PT association was good with no reported cases of ulcerative enterocolitis in 265 treated newborns. CONCLUSION: IVIG associated with PT reduces the need for ET and the duration of PT in newborns with hyperbilirubinemia due to ABO hemolytic disease. Their efficacy and good tolerance prompt consideration of IVIg as a therapeutic adjuvant to PT in severe hemolytic hyperbilirubinemia due to ABO incompatibility. PMID- 25125033 TI - [Lacidipine efficacy and safety for high blood pressure treatment in pediatric oncohematology]. AB - In adults, lacidipine seems to have no CYP3A4-inhibiting action. This particular characteristic makes it advantageous when combined with drugs metabolized by CYP3A4, such as cyclosporine. Until now, no data on the efficacy or safety of this calcium antagonist have been available in children. Thirty-nine hypertensive children (age: 0.13-14 years) receiving lacidipine in oncohematology for a mean of 75 days were included in this retrospective study. The causes of high blood pressure were renal tumor (n=7), catecholamine-secreting tumor (n=4), corticoid treatment (n=5), and cyclosporine treatment (n=23). An initial dosage of 0.05 mg/kg/day was sufficient for 41% of the patients. The remaining patients needed to increase the dosage, by steps of 0.03 mg/kg/day, until reaching an average effective dosage of 0.1 mg/kg/day. Lacidipine significantly decreased blood pressure by 30 (+/-14) mmHg for systolic blood pressure and by 26 (+/-13) mmHg for diastolic blood pressure. A medication plan with twice-daily administration was not significantly more effective than a single administration per day. Lacidipine was well tolerated, and no toxicity-related withdrawal of treatment occurred. For 22 patients treated with both cyclosporine and lacidipine, renal function was not disturbed over time, suggesting its preservation by lacidipine. No significant increase in cyclosporine blood concentration was detected. Lacidipine seems to be an effective calcium antagonist in pediatric oncohematology, is well tolerated, has a kidney-protector effect and no drug interaction when combined with cyclosporine. PMID- 25125034 TI - [Lactic acidosis in a child with acute severe asthma]. AB - Lactic acidosis is a recognized event in adult patients with acute severe asthma (ASA). Only a few cases have been reported in children. Hereinafter is reported the case of a 2-year-old girl hospitalized in the pediatric intensive care unit for ASA, which was treated with high-flow oxygen therapy and intravenous methylprednisolone and salbutamol. During hospitalization, she had metabolic acidosis with a 7.29 pH, a 26mmHg hypocapnia, and a decrease in bicarbonates to 12 mmol/L. The anion gap was increased to 20 mmol/L and lactates to 8 mmol/L. The work-up for a congenital metabolic disease was normal. Progression was propitious with spontaneous improvement of lactic acidosis, and the child was discharged from the intensive care unit after 72 h. The origin of lactic acidosis during ASA seems to be multifactorial. Although its recovery can be spontaneous, it is important to know how to identify it because it can worsen respiratory symptoms and can lead to incongruous therapeutic escalation. PMID- 25125036 TI - A silenced spring? PMID- 25125035 TI - A post hoc analysis of subgroup outcomes and creatinine in the phase III clinical trial (EMPOWER) of dexpramipexole in ALS. AB - Our objective was to compare the phase II and phase III (EMPOWER) studies of dexpramipexole in ALS and evaluate potential EMPOWER responder subgroups and biomarkers based on significant inter-study population differences. In a post hoc analysis, we compared the baseline population characteristics of both dexpramipexole studies and analyzed EMPOWER efficacy outcomes and laboratory measures in subgroups defined by significant inter-study differences. Results showed that, compared with phase II, the proportion of El Escorial criteria (EEC) definite participants decreased (p = 0.005), riluzole use increased (p = 0.002), and mean symptom duration increased (p = 0.037) significantly in EMPOWER. Baseline creatinine (p < 0.001) and on-study creatinine change (p < 0.001) correlated significantly with ALSFRS-R in EMPOWER. In the EMPOWER subgroup defined by EEC-definite ALS, riluzole use, and < median symptom duration (15.3 months), dexpramipexole-treated participants had reduced ALSFRS-R slope decline (p = 0.015), decreased mortality (p = 0.011), and reduced creatinine loss (p = 0.003). In conclusion, significant differences existed between the phase II and EMPOWER study populations in ALS clinical trials of dexpramipexole. In a post hoc analysis of EMPOWER subgroups defined by these differences, potential clinical benefits of dexpramipexole were identified in the subgroup of riluzole-treated, short-symptom duration, EEC-definite ALS participants. Creatinine loss correlated with disease progression and was reduced in dexpramipexole-treated participants, suggesting it as a candidate biomarker. PMID- 25125038 TI - Biofouling ecology as a means to better understand membrane biofouling. AB - Despite more than a decade of worldwide research on membrane fouling in membrane bioreactors, many questions remain to be answered. Biofouling, which is referred to as the unwanted deposition and growth of biofilms, remains the main problem. Due to its complexity, most of the existing anti-biofouling strategies are not completely successful. To unravel this complexity and finally to developed well adapted control strategies, a microbial-based description of the biofouling development is needed. Therefore, in this review, the biofouling formation will be described as a typical biofilm formation in five steps including the formation of a conditioning film, the bacterial attachment, the production of extracellular polymeric substances, the biofilm maturation, and the bacterial detachment. Moreover, important processes such as hydrodynamics and bacterial communication or quorum sensing will be taken into account. It is finally discussed whether biofouling formation is an active or inactive biofilm process together with suggestion for further research. PMID- 25125037 TI - Degradation of off-gas toluene in continuous pyrite Fenton system. AB - Degradation of off-gas toluene from a toluene reservoir and a soil vapor extraction (SVE) process was investigated in a continuous pyrite Fenton system. The removal of off-gas toluene from the toluene reservoir was >95% by 8h in the pyrite Fenton system, while it was ~97 % by 3h in classic Fenton system and then rapidly decreased to initial level by 8h. Continuous consumption of low Fe(II) concentration dissolved from pyrite surface (0.05-0.11 mM) was observed in the pyrite Fenton system, which can lead to the effective and successful removal of the gas-phase toluene due to stable production of OH radical (OH). Inhibitor and spectroscopic test results showed that OH was a dominant radical that degraded gas-phase toluene during the reaction. Off-gas toluene from the SVE process was removed by 96% in the pyrite Fenton system, and remnant toluene from rebounding effect was treated by 99%. Main transformation products from toluene oxidation were benzoic acid (31.4%) and CO2 (38.8%) at 4h, while traces of benzyl alcohol (1.3%) and benzaldehyde (0.7%) were observed. Maximum operation time of continuous pyrite Fenton system was estimated to be 56-61 d and its optimal operation time achieving emission standard was 28.9 d. PMID- 25125039 TI - Escherichia coli W shows fast, highly oxidative sucrose metabolism and low acetate formation. AB - Sugarcane is the most efficient large-scale crop capable of supplying sufficient carbon substrate, in the form of sucrose, needed during fermentative feedstock production. However, sucrose metabolism in Escherichia coli is not well understood because the two most common strains, E. coli K-12 and B, do not grow on sucrose. Here, using a sucrose utilizing strain, E. coli W, we undertake an in depth comparison of sucrose and glucose metabolism including growth kinetics, metabolite profiling, microarray-based transcriptome analysis, labelling-based proteomic analysis and (13)C-fluxomics. While E. coli W grew comparably well on sucrose and glucose integration of the omics, datasets showed that during growth on each carbon source, metabolism was distinct. The metabolism was generally derepressed on sucrose, and significant flux rearrangements were observed in central carbon metabolism. These included a reduction in the flux of the oxidative pentose phosphate pathway branch, an increase in the tricarboxylic acid cycle flux and a reduction in the glyoxylate shunt flux due to the dephosphorylation of isocitrate dehydrogenase. But unlike growth on other sugars that induce cAMP-dependent Crp regulation, the phosphoenol-pyruvate-glyoxylate cycle was not active on sucrose. Lower acetate accumulation was also observed in sucrose compared to glucose cultures. This was linked to induction of the acetate catabolic genes actP and acs and independent of the glyoxylic shunt. Overall, the cells stayed highly oxidative. In summary, sucrose metabolism was fast, efficient and led to low acetate accumulation making it an ideal carbon source for industrial fermentation with E. coli W. PMID- 25125040 TI - Cellular fatty acid profile and H(+)-ATPase activity to assess acid tolerance of Bacillus sp. for potential probiotic functional attributes. AB - The present study has been focused widely on comparative account of probiotic qualities of Bacillus spp. for safer usage. Initially, 170 heat resistant flora were isolated and selected for non-pathogenic cultures devoid of cytK, hblD, and nhe1 virulence genes. Subsequently, through biochemical tests along with 16S rRNA gene sequencing and fatty acid profiling, the cultures were identified as Bacillus megaterium (AR-S4), Bacillus subtilis (HR-S1), Bacillus licheniformis (Csm1-1a and HN-S1), and Bacillus flexus (CDM4-3c and CDM3-1). The selected cultures showed 70-80 % survival under simulated gastrointestinal condition which was also confirmed through H(+)-ATPase production. The amount of H(+)-ATPase increased by more than 2-fold when grown at pH 2 which support for the acid tolerance ability of Bacillus isolates. The study also examined the influence of acidic pH on cellular fatty acid composition of Bacillus spp. A remarkable shift in the fatty acid profile was observed at acidic pH through an increased amount of even numbered fatty acid (C16 and C18) in comparison with odd numbered (C15 and C17). Additionally, the cultures exhibited various probiotic functional properties. Overall, the study increases our understanding of Bacillus spp. and will allow both industries and consumers to choose for well-defined probiotic with possible health benefits. PMID- 25125041 TI - Differential contributions of two SARP family regulatory genes to indigoidine biosynthesis in Streptomyces lavendulae FRI-5. AB - The Streptomyces antibiotic regulatory protein (SARP) family regulators have been shown to control the production of secondary metabolites in many Streptomyces species as the most downstream regulators in the regulatory cascade. Streptomyces lavendulae FRI-5 produces a blue pigment (indigoidine) together with two types of antibiotics: D-cycloserine and the nucleoside antibiotics. The production of these secondary metabolites is governed by a signaling system consisting of a gamma-butyrolactone, IM-2 [(2R,3R,1'R)-2-1'-hydroxybutyl-3-hydroxymethyl-gamma butanolide], and its cognate receptor, FarA. Here, we characterized two regulatory genes of the SARP family, farR3 and farR4, which are tandemly located in the proximal region of farA. farR3 is transcribed both as a monocistronic RNA and as a bicistronic farR4-farR3 mRNA, and the expression profile is tightly controlled by the IM-2/FarA system. Loss of farR3 delayed and decreased the production of indigoidine without any changes in the transcriptional profile of other far regulatory genes, indicating that FarR3 positively controls the biosynthesis of indigoidine and is positioned in the downstream region of the IM 2/FarA signaling system. Meanwhile, loss of farR4 induced the early production of IM-2 by increasing transcription of an IM-2 biosynthetic gene, farX, indicating that FarR4 negatively controls the biosynthesis of IM-2. Thus, our results suggested differential contributions of the SARP family regulators to the regulation of secondary metabolism in S. lavendulae FRI-5. This is the first report to show that an SARP family regulator is involved in the biosynthesis of a signaling molecule functioning at the most upstream region of the regulatory cascade for Streptomyces secondary metabolism. PMID- 25125042 TI - C7-prenylation of tryptophanyl and O-prenylation of tyrosyl residues in dipeptides by an Aspergillus terreus prenyltransferase. AB - During our search for novel prenyltransferases, a putative gene ATEG_04218 from Aspergillus terreus raised our attention and was therefore amplified from strain DSM 1958 and expressed in Escherichia coli. Biochemical investigations with the purified recombinant protein and different aromatic substrates in the presence of dimethylallyl diphosphate revealed the acceptance of all the tested tryptophan containing cyclic dipeptides. Structure elucidation of the main enzyme products by NMR and MS analyses confirmed the attachment of the prenyl moiety to C-7 of the indole ring, proving the identification of a cyclic dipeptide C7 prenyltransferase (CdpC7PT). For some substrates, reversely C3- or N1-prenylated derivatives were identified as minor products. In comparison to the known tryptophan-containing cyclic dipeptide C7-prenyltransferase CTrpPT from Aspergillus oryzae, CdpC7PT showed a much higher substrate flexibility. It also accepted cyclo-L-Tyr-L-Tyr as substrate and catalyzed an O-prenylation at the tyrosyl residue, providing the first example from the dimethylallyltryptophan synthase (DMATS) superfamily with an O-prenyltransferase activity towards dipeptides. Furthermore, products with both C7-prenyl at tryptophanyl and O prenyl at tyrosyl residue were detected in the reaction mixture of cyclo-L-Trp-L Tyr. Determination of the kinetic parameters proved that (S)-benzodiazepinedione consisting of a tryptophanyl and an anthranilyl moiety was accepted as the best substrate with a K M value of 204.1 MUM and a turnover number of 0.125 s(-1). Cyclo-L-Tyr-L-Tyr was accepted with a K M value of 1,411.3 MUM and a turnover number of 0.012 s(-1). PMID- 25125043 TI - Two-photon-induced fluorescence in new pi-expanded diketopyrrolopyrroles. AB - Structurally unique pi-expanded diketopyrrolopyrroles (EDPP) were designed and synthesized. Strategic placement of a fluorene scaffold at the periphery of a diketopyrrolopyrrole through tandem Friedel-Crafts-dehydration reactions resulted in dyes with supreme solubility. The structure of the dyes was confirmed by X-ray crystallography verifying a nearly flattened arrangement of the ten fused rings. Despite the extended ring system, the dye still preserved good solubility and was further functionalized by using Pd-catalyzed coupling reactions, such as the Buchwald-Hartwig amination. Photophysical studies of these new functional dyes revealed that they possess enhanced properties when compared with expanded DPPs in terms of two-photon absorption cross-section. It is further demonstrated that in addition to the initial diacetals, the final electrophilic cyclization step can also be applied to diketones. By placing two amine groups at peripheral positions of the resulting dyes, values of two-photon absorption cross-section on the level of 2000 GM around 1000 nm were achieved, which in combination with high fluorescence quantum yield (Phifl ), generated a two-photon brightness of approximately 1600 GM. These characteristics in combination with strong red emission (665 nm) make these new pi-expanded diketopyrrolopyrroles of major promise as two-photon dyes for bioimaging applications. Finally, the corresponding N-alkylated DPPs displayed a solid-state fluorescence. PMID- 25125044 TI - An enhanced photocatalytic response of nanometric TiO2 wrapping of Au nanoparticles for eco-friendly water applications. AB - We propose a ground-breaking approach by an upside-down vision of the Au/TiO2 nano-system in order to obtain an enhanced photocatalytic response. The system was synthesized by wrapping Au nanoparticles (~8 nm mean diameter) with a thin layer of TiO2 (~4 nm thick). The novel idea of embedding Au nanoparticles with titanium dioxide takes advantage of the presence of metal nanoparticles, in terms of electron trapping, without losing any of the TiO2 exposed surface, so as to favor the photocatalytic performance of titanium dioxide. A complete structural characterization was made by scanning electron microscopy, transmission electron microscopy and X-ray diffraction. The remarkable photocatalytic performance together with the stability of the nano-system was demonstrated by degradation of the methylene blue dye in water. The non-toxicity of the nano-system was established by testing the effect of the material on the reproductive cycle of Mytilus galloprovincialis in an aquatic environment. The originally synthesized material was also compared to conventional TiO2 with Au nanoparticles on top. The latter system showed a dispersion of Au nanoparticles in the liquid environment, due to their instability in the aqueous solution that clearly represents an environmental contamination issue. Thus, the results show that nanometric TiO2 wrapping of Au nanoparticles has great potential in eco-friendly water/wastewater purification. PMID- 25125045 TI - In vitro assessment of the direct effect of laquinimod on basic functions of human neural stem cells and oligodendrocyte progenitor cells. AB - Laquinimod is an orally active immunomodulatory small molecule that has shown clear clinical benefit in trials for relapsing-remitting multiple sclerosis and in experimental rodent models that emulate multiple sclerosis (MS). Studies in healthy mice, and in mice with experimental autoimmune encephalomyelitis, have demonstrated that laquinimod is capable of entering the central nervous system. It is therefore important to determine if laquinimod is capable of a direct influence on basic functions of neural stem cells (NSC) or oligodendrocyte progenitor cells (OPC)--cells critical for myelin repair in MS. In order to address this question, a series of experiments was conducted to determine the effect of exogenous laquinimod on viability, proliferation, migration and differentiation of human NSC and OPC in vitro. These data show, for the first time in cells of human origin, that direct, short-term interaction between laquinimod and NSC or OPC, in an isolated in vitro setting, is not detrimental to the basic cellular function of these cells. PMID- 25125046 TI - Longitudinally extensive optic neuritis in neuromyelitis optica spectrum disorder. AB - BACKGROUND: Neuomyelitis optica, sarcoid, and multiple sclerosis can all cause optic neuritis. Further means of distinguishing the causes of optic neuritis among these etiologies would be valuable for the clinician. METHODS: This is a retrospective, cohort study from a single university based hospital and neuro ophthalmology clinic. Blinded interpretation of orbit MRIs was performed on patients with acute optic neuritis from multiple sclerosis (n=25), sarcoid (n=5) and neuromyelitis optica spectrum disorder (n=6). RESULTS: A length of >40 mm anterior visual pathway enhancement distinguished neuromyelitis optica spectrum disorder from multiple sclerosis (p=0.0376). No statistically significant differences were found for presence of pain or papillitis, however there was a trend for bilateral involvement and chiasmal involvement in neuromyelitis optica spectrum disorder compared to multiple sclerosis. CONCLUSIONS: In acute optic neuritis, enhancing anterior visual pathway lesion length >40 mm helps differentiate neuromyelitis optica spectrum disorder from multiple sclerosis. This degree of involvement can be considered longitudinally extensive optic neuritis. Further characterization is necessary as this degree of enhancement occurs in other clinical syndromes besides neuromyelitis optica. PMID- 25125047 TI - Does early verbal fluency decline after STN implantation predict long-term cognitive outcome after STN-DBS in Parkinson's disease? AB - BACKGROUNDS: An early and transient verbal fluency (VF) decline and impairment in frontal executive function, suggesting a cognitive microlesion effect may influence the cognitive repercussions related to subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: Neuropsychological tests including semantic and phonemic verbal fluency were administered both before surgery (baseline), the third day after surgery (T3), at six months (T180), and at an endpoint multiple years after surgery (Tyears). RESULTS: Twenty-four patients (mean age, 63.5 +/- 9.5 years; mean disease duration, 12 +/- 5.8 years) were included. Both semantic and phonemic VF decreased significantly in the acute post-operative period (44.4 +/- 28.2% and 34.3 +/- 33.4%, respectively) and remained low at 6 months compared to pre-operative levels (decrease of 3.4 +/- 47.8% and 10.8 +/- 32.1%) (P < 0.05). Regression analysis showed phonemic VF to be an independent factor of decreased phonemic VF at six months. Age was the only independent predictive factor for incident Parkinson's disease dementia (PDD) (F (4,19)=3.4, P<0.03). CONCLUSION: An acute post-operative decline in phonemic VF can be predictive of a long-term phonemic VF deficit. The severity of this cognitive lesion effect does not predict the development of dementia which appears to be disease-related. PMID- 25125048 TI - Meta-analysis of the association between two neprilysin gene polymorphisms and Alzheimer's disease. AB - OBJECTIVE: The aim of this study is to evaluate the association between two neprilysin variants (rs989692 and rs3736187) and Alzheimer's disease (AD). METHODS: All eligible studies were searched in PubMed and Embase from inception to July 2014. Data was extracted by two investigators independently. The complete overdominant model (CC+TT vs. CT) and co-dominant model (GG vs. AA and GA vs. AA) were used for rs989692 and rs3736187, respectively. A comparison of allele frequencies was also conducted. RESULTS: Six studies containing 2555 AD patients and 1914 controls were included for rs989692 polymorphisms. The pooled odds ratio (OR) and confidence interval (CI) suggested that rs989692 polymorphisms were not associated with AD based on the current published studies (C vs. T, OR = 1.01, 95% CI = 0.85-1.19; CC+TT vs. CT, OR = 0.89, 95% CI = 0.78-1.01). Five studies containing 2438 AD patients and 1452 controls were identified for rs3736187 polymorphisms (G vs. A, OR = 0.77, 95% CI = 0.66-0.91; GG vs. AA, OR = 0.38, 95% CI = 0.19-0.77; GA vs. AA, OR = 0.81, 95% CI = 0.61-0.99). The result showed that rs3736187 polymorphisms were likely associated with the decreased risk of AD. CONCLUSIONS: This meta-analysis indicates that rs3736187 (A/G) polymorphisms may be a potential beneficial single nucleotide polymorphism (SNP), which are associated with a decreased risk in AD. Further larger scale studies are necessary to validate gene-to-gene interactions and to define the association of neprilysin polymorphisms with AD. PMID- 25125049 TI - Expression of suppressor of cytokine signaling 3 in cerebrospinal fluid after subarachnoid hemorrhage. AB - BACKGROUND: IL-6 is a proinflammatory cytokine reported to play an important role in the induction of cerebral vasospasm after subarachnoid hemorrhage (SAH). Suppressor of cytokine signaling 3 (SOCS3) is known to act as an inhibitor of signal transduction of IL-6. However, there have been no reports on the expression of SOCS3 in cerebrospinal fluid (CSF) after SAH. FINDINGS: The concentration of IL-6 was measured serially up until day 10, in CSF of eight patients with SAH. CSF samples obtained from patients suffering from an unruptured aneurysm were used as controls. The expression of SOCS3 in CSF was further examined by immunoprecipitation methods. Concentrations of IL-6 in CSF increased immediately after the onset of SAH and remained chronically elevated over control values. SOCS3 was significantly expressed in CSF on days 1 to 3 after SAH. CONCLUSIONS: Our findings suggest that SOCS3 regulates IL-6 signaling as an antagonist in CSF, immediately following SAH. As the expression of SOCS3 decreases after day 5, IL-6 signals might then be more easily transmitted, presumably resulting in cerebral vasospasm. PMID- 25125051 TI - Apixaban versus enoxaparin in elective major orthopedic surgery: a clinical review. AB - Despite current guidelines recommendations about anticoagulant prophylaxis, many studies have shown an high venous thromboembolism (VTE) incidence in patients undergoing total hip and knee arthroplasty. A number of anticoagulants are currently available, but they have some limitations that affect their applicability and consequently their effectiveness. Several new oral anticoagulants (NOACs) have been developed in an attempt to overcome these limitations. Apixaban is a NOAC that selectively inhibits the coagulation factor Xa; it is approved for the prevention of VTE after total hip replacement and total knee replacement surgery. This review examines the results of main trials designed to test efficacy and safety of apixaban in major elective orthopedic surgery. PMID- 25125050 TI - Amyloid-beta(1-42) protofibrils stimulate a quantum of secreted IL-1beta despite significant intracellular IL-1beta accumulation in microglia. AB - Neuroinflammation is a characteristic feature of the Alzheimer's disease (AD) brain. Significant inflammatory markers such as activated microglia and cytokines can be found surrounding the extracellular senile plaques predominantly composed of amyloid-beta protein (Abeta). Several innate immune pathways, including Toll like receptors (TLRs) and the NLRP3 inflammasome, have been implicated in AD inflammation. Abeta plays a primary role in activating these pathways which likely contributes to the progressive neurodegeneration in AD. In order to better understand the complexities of this interaction we investigated the inflammatory response of primary microglia to Abeta(1-42) protofibrils. Abeta(1-42) protofibrils triggered a time- and MyD88-dependent process that produced tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) mRNA, and intracellular pro and mature forms of IL-1beta protein. The accumulation of both IL-1beta forms indicated that Abeta(1-42) protofibrils were able to prime and activate the NLRP3 inflammasome. Surprisingly, Abeta-induced accumulation of intracellular mature IL-1beta did not translate into greater IL-1beta secretion. Instead, we found that Abeta elicited a quantized burst of secreted IL-1beta and this process occurred even prior to Abeta priming of the microglia suggesting a basal level of either pro or mature IL-1beta in the cultured primary microglia. The IL-1beta secretion burst was rapid but not sustained, yet could be re-evoked with additional Abeta stimulation. The findings from this study demonstrated multiple sites of IL-1beta regulation by Abeta(1-42) protofibrils including TLR/MyD88-mediated priming, NLRP3 inflammasome activation, and modulation of the IL-1beta secretory process. These results underscore the wide-ranging effects of Abeta on the innate immune response. PMID- 25125052 TI - [Magnesium, diabetes and metabolic syndrome]. PMID- 25125053 TI - [Reduction of omalgia in laparoscopic cholecystectomy: clinical randomized trial ketorolac vs ketorolac and acetazolamide]. AB - BACKGROUND: Laparoscopy cholecystectomy for the surgical treatment of cholelithiasis has been considered the gold standard. The referred pain to the shoulder (omalgia) may be present to 63% of the patients and limits outpatient management. OBJECTIVE: The study was to evaluate the usefulness of acetazolamide associated with ketorolac for reduction of the omalgia to minimally invasive treatment. METHODS: We performed a clinical trial, randomized, double blind in patients undergoing laparoscopic cholecystectomy to assess the reduction of post operative omalgia comparing ketorolac and ketorolaco+acetazolamida. 31 patients in each group were studied. The study group: 250 mg of acetazolamide before anesthetic induction and 30 mg of ketorolac in the immediate postoperative period. CONTROL GROUP: one tablet of placebo prior to the anesthetic induction and 30 mg of ketorolac in the immediate postoperative. The presence of omalgia was assessed using the analog visual scale. The variables recorded included: age, sex, flow of carbon dioxide intra-abdominal pressure, surgical time, urgent or elective surgery, omalgia, severity of pain evaluated by analog visual scale, addition analgesia. RESULTS: Both groups were homogeneous and statistical analysis showed no differences in the variables studied. The omalgia in the study group was presented at 9.67% and in the group control was the 58.06% (p < 0.001). CONCLUSION: 250 mg oral acetazolamide associated 30 mg of ketorolac reduces significantly the development of omalgia in patients undergoing laparoscopic cholecystectomy. PMID- 25125054 TI - [Bile duct lesions repaired with peritoneal tube grafts]. AB - BACKGROUND: A significant number of people suffer iatrogenic bile duct injury during laparoscopic cholescystectomy. Biliary-digestive bypass may be complicated by stenosis and biliary sepsis, affecting both quality of life and life expectancy. To avoid bypass synthetic grafts have been used, which are expensive. OBJECTIVE: Evaluating autologous implantation of peritoneus as alternative of bile duct repair. METHODS: Under general anesthesia, ten New Zealand adult rabbits were operated, common bile duct approached and sectioned underneath the cystic duct followed by a liver biopsy. An autologous graft was built of peritoneum and graft-bile duct proximal and distal end-to-end anastomosis done. Animals were followed-up by weekly bilirrubin and transferases. Rabbits were scheduled euthanized and a liver biopsy done for histological examinations. RESULTS: Autologous graft was easy to create and all rabbits survived. They did not develop jaundice or alterations in their normal habits. At necropsy, autologous grafts were removed and no signs of occlusion were noticed. Moderate short-term liver damage was observed but long-term damage was negligible. Bileoma and pyogenic liver abscess were observed in two animals, respectively. DISCUSSION: Our results favourably match well-known procedures used for bile duct repair, especially in cases of severe injury (Bismuth-Strasberg E1-3): it seems less complicated than biliary-digestive bypass, not as expensive as synthetic grafts, and much easier to build than human amnion graft. CONCLUSION: Interposing an autologous graft of peritoneum is an easy-to-create surgical procedure and circumferential bile duct injuries were adequately repaired. PMID- 25125055 TI - [Analgesic efficacy of the incisional infiltration of ropivacaine vs ropivacaine with dexamethasone in the elective laparoscopic cholecystectomy]. AB - BACKGROUND: Incisional pain is the main obstacle for elective laparoscopic cholecystectomy as an outpatient. We evaluated the analgesic efficacy of local infiltration of ropivacaine with dexamethasone (Rop/Dx), compared with ropivacaine (Rop) alone, during the first 24 hours postoperative of this surgery. Our hypothesis is that incisional pain intensity will be lower in patients of the group Rop/Dx. METHODS: In a randomized, controlled, double-blind trial clinical, 80 patients were divided into two groups. Group Rop (n= 40) received pre and post incisional infiltration with 150 mg of ropivacaine in 8 mL of 0.9% saline, while group Rop/Dx (n= 40) received 150 mg of ropivacaine with 8 mg of dexamethasone in 6 mL of 0.9% saline. The intensity of pain at rest and movement was assessed at 2, 4, 8, 12 and 24 hours postoperatively by a numerical rating scale of 11 points. RESULTS: Incisional pain scores in group Rop/Dx were significantly lower, compared to the group Rop, at 12 hours (p= 0.05) and 24 hours (p= 0.01) at rest and at 12 hours (p= 0.04) and 24 hours (p= 0.01) during movement postoperatively. CONCLUSIONS: We found initial evidence that ropivacaine with dexamethasone for local infiltration decreased incisional pain intensity after 12 hours post elective laparoscopic cholecystectomy with a good safety profile. PMID- 25125056 TI - [Risk factors and evolution of enterocutaneous fistula after terminal ostomy takedown]. AB - BACKGROUND: End-ileostomy or colostomies are constructed for source control in patients with severe abdominal sepsis. After takedown, enterocutaneous fistula represents one of the most feared complications. METHODS: A prospective base was created with all patients that underwent, during a 90 month period, end-ileostomy or colostomy takedown after abdominal sepsis. Pre-, intra- and postoperative data were obtained to identify the factors related to enterocutaneous fistula. RESULTS: There were 293 patients. Thirty patients (10%) developed enterocutaneous fistulas. In twenty-four patients the site was at the anastomosis. Identified risk factors related to enterocutaneous fistula were ASA score III or higher (p< 0.01), ostomy takedown >365 days after its creation (p< 0.05), reoperation (p< 0.001) and anastomotic dehiscence (p< 0.001). Of these patients, twenty (67%) had spontaneous closure of the fistula, and three more (10%) had surgical closure, and three patients (10%) died. CONCLUSIONS: Ten percent of patients develop enterocutaneous fistula after end-ileostomy or colostomy takedown. Patient selection and delaying time of surgery to obtain complete recovery of the patient are the most important factors to avoid this complication. Prognosis is related to the characteristics of the fistula (output and site) and medical treatment. PMID- 25125057 TI - [Financial expenses incurred by herniated disk in health professionals]. AB - BACKGROUND: Long-term sick leave by illeness is cause of financial expences and worker's loss of productivity. OBJECTIVE: To evaluate the financial expense incurred by spinal disk herniation in health professionals. METHODS: 3000 health professionals of the Instituto Mexicano del Seguro Social work in Tecate, Tijuana and Rosarito, cities of Baja California, Mexico. During 2009-2011, 1070 health professionals had long sick leave certificates and 48 had a cervical or lumbar disk herniation. We evaluated the total days of absenteeism in comparison with the absenteeism days suggested by the Medical Disability Advisor. RESULTS: Of the 48 spinal herniated disks, 54% were cervical and 65% had surgical management. The mean (+/- SD) days of absence was 125 +/- 84 and 24 (50%) of the spinal herniated disks exceeded the Medical Disability Advisor disability duration parameters, in 6 (26%), 12 (52%), and 5 (22%) patients due to no diagnostic concordance, diagnosis delay and residual pain, respectively. The total cost of the spinal herniated disks that extended outside of the Medical Disability Advisor disability duration parameters was 683,026 pesos versus 367,081 pesos of the spinal herniated disks that did not exceed the Medical Disability Advisor disability duration parameters. After 12 months of follow-up, 9 (18.8%) continue with sick leave and 2 (4%) had permanent disability. CONCLUSIONS: In patients with a spinal herniated disk, the costs of subsidies were two-fold more due principally to a not diagnostic agreement. PMID- 25125058 TI - [Temporary disability in operated spine patients. Preliminary report]. AB - BACKGROUND: The spinal injuries in workers have become a large scale health problem. The purpose of this study is to review the differences in the spine pathologies from incapacity to work, as well as factors that could alter the recovery time and the possibility of returning the patient to work. METHODS: Statistical preliminary review study in 37 patients enrolled in the Instituto Mexicano del Seguro Social, workers, undertaken to spinal pathology surgery, comparing days of incapacity with proposed internationally, as well as his return to work. RESULTS: The results show that 37% of the patients studied are still active in the social security, 2 years after surgery. The days of disability generated by the pathology in this study group (212.3 days) are significantly higher than what is set on the Medical Disability Advisor (56 days, almost 4 times more). CONCLUSION: The study shows the need to develop the same analysis in other hospitals, comparing the proportion of cases that return to the work and total disability times for diagnostics. PMID- 25125059 TI - [New technologies in minimally invasive surgery training: what do surgeons demand?]. AB - BACKGROUND: Minimally invasive surgery might greatly benefit from the Information and Communications Technologies. The objective of this work is to determine the better approach to include those technologies, in particular an e-Learning platform, into an in-person training course. METHODS: An online survey was sent to all participants in any of the laparoscopic training courses at Jesus Uson Minimally Invasive Surgery Centre. This survey included questions regarding new technologies used for training. Once all data were gathered, a descriptive analysis was performed. RESULTS: 382 questionnaires were sent of which 102 were correctly received back. This means a response rate equal to 30%. Current theoretical training means are watching surgical videos (85-83.3%) and assisting to in-person training courses (77-75.5%). Participants rated as useful the use of new technologies for training (4.1 +/- 0.9) and they would mainly use it both before and after assisting to an in-person training course (80-78.4%). CONCLUSIONS: It is proposed a methodology that provides participants with didactic resources based on surgical videos, both before and after assisting to an in-person training course. Through the application of this methodology, an improvement and reduction of the time that surgeons expend in training is aimed. PMID- 25125060 TI - [Pyramid training model in laparoscopic surgery]. AB - BACKGROUND: Minimally invasive surgery implementation requires a regulated and orderly learning process. METHODS: Jesus Uson Minimally Invasive Surgery Centre promotes a pyramid training model structured into four levels: training of basic and advanced skills in physical simulator (level 1), training of anatomical protocols and advanced skills with animal models (level 2) training advanced procedural skills with tele-surgical applications (level 3), and training in the operating room (level 4). Training provided at levels 1 and 2 is described and evaluated. RESULTS: 4284 participants have been trained in laparoscopy at our institution. 95.5% surgeons: 49% gastroenterologists, 30% urologists, and 14% gynecologist (14%). 77% of celebrated courses consisted of 20 hours training (8 at level 1 and 12 at level 2). 94.37% of participants considered pyramid model as highly suitable, scoring 9.5 on a scale 1-10 for the model and for the simulation quality. 82.7% perceived the improvement in their laparoscopic skills and 99.56% recommend this training program to other surgeons. DISCUSSION: There are no unified criteria between different training programs but most of them measure laparoscopic skills based on time of execution, quality or mistakes of the exercise, and the student satisfaction test. CONCLUSION: The pyramid training model lead to the acquisition of necessary laparoscopic skills to perform safely advanced minimally invasive techniques. PMID- 25125061 TI - [Intracranial tumor behavior of plasma cell neoplasms. Report of 2 cases and literature review]. AB - BACKGROUND: Multiple myeloma is a plasmatic cell neoplasm that is characterized by skeletal destruction, renal failure, anemia and hypercalcemia. The skull plasmacytomas represent less than 1% of the head and neck tumors, they can be the primary lesion or occur as a secondary manifestation of multiple myeloma in 20 30% of the patients, or they can even manifest several years later after the diagnosis of plasmacytoma. Although some of the lesions may be surgically accessible, the aggressive natural behavior will complicate the evolution of the patients. We present two cases of Mexican women with intracranial plasmacytomas, one of them associated with multiple myeloma. CLINICAL CASES: The first case was a 24 year-old woman diagnosed with a multiple myeloma with plasmacytic plasmablastic bone infiltration that was removed in 90%. She presented a local recurrence that required a second intervention for removal. The second case was a 62 year-old female with a malignant intracranial tumor of plasma cells that was totally resected. Both patients received adjuvant treatment based on chemotherapy and radiation therapy with favorable results. The patients died at 5 and 1.5 years respectively due to renal failure secondary to systemic disease. CONCLUSIONS: We propose chemotherapy and radiation therapy as an essential part of treatment for this condition, as the aggressive behavior of the neoplasms can complicate the evolution, despite being surgically accessible. PMID- 25125062 TI - [Adnexal neoplasms in the context of skin cancer: trichilemmal carcinoma. Apropos of a case]. AB - BACKGROUND: The trichilemmal carcinoma is a rare malignant neoplasm, whose origin lies in the annexes of the skin, because of its low prevalence often confused with other dermal tumors, the differential diagnosis is not easy and is usually made by exclusion; in theory, its behavior is slow with little tendency to send both regional lymph node metastasis and systemic. Due to the limited number of cases there is no consensus on the prognosis, although it is generally considered good. The aim of this report is to show a case that, contrary to previous reports, the clinical presentation is aggressive with large soft tissue tumor infiltration around the site of origin in a patient without risk factors for skin cancer. CLINICAL CASE: Male patient, 65 years old with cytologic diagnosis of carcinoma in a preprarotideal facial tumor, characteristics at diagnosis were infiltration of the facial skin, ear, and parotid gland. Complete block resection was performed, radical parotiroidectomy and radical neck dissection; the soft tissue defect was covered with a pediculated flap. The evolution was satisfactory it follow-up short though. We evaluated the experience in the literature regarding the prognosis and treatment of these patients. CONCLUSION: Trichilemmal carcinoma can be fully invasive behavior prognosis is difficult to know and probably depends on the clinical stage at diagnosis. PMID- 25125063 TI - [Acute pancreatitis and afferent loop syndrome. Case report]. AB - BACKGROUND: The afferent syndrome loop is a mechanic obstruction of the afferent limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea and vomiting, abdominal distension, without peritoneal irritation sings. Amylase 1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation of afferent loop, pancreas with diffuse enlargement diagnostic of acute pancreatitis secondary an afferent loop syndrome. CONCLUSION: The afferent loop syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction, with a mortality of up to 57%, the obstruction lead accumulation of bile, pancreatic and intestinal secretions, increasing the pressure and resulting in afferent limb, bile conduct and Wirsung conduct dilatation, triggering an inflammatory response that culminates in pancreatic inflammation. The severity of the presentation is related to the degree and duration of the blockage. PMID- 25125064 TI - [Sigmoid diverticulitis in adolescent. Case report]. AB - BACKGROUND: Few cases have been reported in children and adolescents of sigmoid diverticulitis. Most of the case reports in medical literature are associated with true congenital diverticula and genetic diseases of collagen synthesis. CLINICAL CASE: 13 year-old female who was admitted to General and Endoscopic Surgery service with diagnosis of complicated appendicitis. Laparotomy was performed finding complicated sigmoid diverticular disease. Lavage, sigmoidectomy and primary anastomosis were performed. The histopathological findings reported a perforated pseudo-diverticulum of the sigmoid colon with peritonitis. The patient was discharged 72 hours after surgery and no complications were reported. CONCLUSION: There are only case reports about colonic diverticulitis in children and adolescents, and its etiology has not yet been well established. This patient had sigmoid pseudo-diverticula and did not present genetic concomitant disease. This case is an exception to data reported on literature about diverticular disease in this population. PMID- 25125065 TI - [Experience in kidney transplantation without blood transfusion: kidney transplantation transfusion-free in Jehovah's Witnesses. First communication in Mexico]. AB - BACKGROUND: Jehovah's Witness refuse blood transfusion, but they accept organ transplantation, albumin, immunoglobulin, vaccines and clotting factors. CLINICAL CASES: We present 3 kidney transplants in Jehovah's Witness patients (two male and one female) without blood transfusion, with a mean age of 31.33 years and a mean body mass index of 20.99 kg/m(2). All patients underwent pretransplant peritoneal dialysis for an average of 52.3 months. Two transplants came from living donors and one from a deceased donor with a cold ischemia of 23 hours. The donors were two females and one male, with a mean age of 34.33 years. All patients received pretransplant erythropoietin and iron dextran and an intraoperative cell saver was used. Hemoglobin, hematocrit, red blood cells and serum creatinine levels, as well as the glomerular filtration at 24 months postransplant were stable. All patients received induction with basiliximab and initial immunosuppression with calcineurin inhibitors. One of the patients had a perirenal hematoma as a complication, which required a surgery 20 days post transplant. At 5, 26 and 36 months postransplant the three patients are alive and with functional grafts. CONCLUSION: It is possible to perform kidney transplantation without transfusion in Jehovah's Witness, obtaining an acceptable global survival without acute rejection. PMID- 25125066 TI - [Vascular injury as a complication of knee arthroscopic surgery. Report of two cases and review of the literature]. AB - BACKGROUND: Arthroscopy of the knee is a surgical performed world-wide considered extremely safe, rates of complication ranging from 0.56 to 8.2%. Vascular complications are even more rare (0.0032%), and generally related to the popliteal artery injury. CLINICAL CASE: We are reporting the cases of two patients who had unsuspected vascular complications after arthroscopy. Both cases presented vascular injuries after elective knee arthroscopy. First case was a patient with thrombosed pseudoaneurysm in the popliteal artery and total section of the popliteal vein, unfortunately the diagnosis was done 72 hrs after knee arthroscopy and finally required amputation, the 2nd case presented popliteal arteriovenous fistula, the diagnosis was done 3 weeks after knee arthroscopy, the patient was successfully treated by resection of the fistula and direct repair of the artery and vein. CONCLUSIONS: Although extremely infrequent, the vascular injury after knee arthroscopy should be remembered as a surgical complication, a low index of suspicion may have caused an unfortunate and untimely delay in diagnosis and treatment with potential risk of leg amputation and death. PMID- 25125067 TI - [Caloric restriction: about its positive metabolic effects and cellular impact]. AB - Caloric restriction, as a 30 to 60% decrease of ad libitum balanced caloric intake, without malnutrition, is the non-genetic strategy that has consistently extended the average and maximum lifespan of most living beings, and it has been tested from unicellular organisms like yeast Saccharomyces cerevisiae to Rhesus primates. In addition, various genetic and pharmacological caloric restriction models have shown to protect against cancer, cardiovascular and neurodegenerative diseases. Primate studies suggest that this intervention delays the onset of age related diseases; in humans, it has physiological, biochemical and metabolic effects decreasing diabetes and cardiovascular disease risk factor. Although currently the mechanism by which caloric restriction has its positive effects at the cellular level is unknown, it has been reported to decrease oxidative stress and increase in mitochondrial biogenesis. PMID- 25125069 TI - Follicular lymphoma of the ocular adnexal region: a nation-based study. AB - PURPOSE: To characterize the clinicopathological features of follicular lymphoma of the ocular adnexal region. METHODS: Retrospective nation-based study of Danish patients with ocular adnexal follicular lymphoma from January 1st 1980 through December 31st 2009. RESULTS: Twenty-four patients with ocular adnexal follicular lymphoma were identified. Fourteen (58%) of the patients were females. The median age was 63 years (range: 42-96 years). Eleven (46%) of the patients had primary ocular adnexal lymphoma, seven (29%) had an ocular adnexal lesion in conjunction with a concurrent systemic lymphoma and six patients (25%) presented with an ocular adnexal relapse. The most frequently affected sites were the lacrimal gland (38%) and the orbit (33%). Thirteen patients (54%) presented with Ann Arbor stage IE lymphoma, four (17%) had stage IIE, two patients (8%) stage IIIE, and five patients (21%) had stage IV lymphoma. Radiotherapy was primarily used in patients with primary lymphoma and those with a stage IE/IIE relapse (82%), while stage IIIE/IV lymphomas most frequently received alkylating chemotherapy (67%). Complete remission was observed in 19 of the patients (79%), but of these 11(58%) had a relapse. The 10-year overall survival for the entire cohort was 59%. The translocation t(14;18) was detected in 16 patients (16/24, 76%). Recurrence was only observed in patients with the t(14;18) (p=0.05, log-rank). CONCLUSIONS: Ocular adnexal follicular lymphoma is more commonly found in elderly female patients. The lacrimal gland is relatively frequently involved. Radiotherapy is the treatment of choice for localized ocular adnexal follicular lymphoma providing a favourable prognosis for majority of patients. PMID- 25125068 TI - Internet-mediated physiotherapy and pain coping skills training for people with persistent knee pain (IMPACT - knee pain): a randomised controlled trial protocol. AB - BACKGROUND: Persistent knee pain in people over 50 years of age is often attributable to knee osteoarthritis (OA), a common joint condition that causes physical and psychological dysfunction. Exercise and pain coping skills training (PCST) can help reduce the impact of persistent knee pain, however, access to health professionals who deliver these services can be challenging. With increasing access to the Internet, remotely delivered Internet-based treatment approaches may provide alternatives for healthcare delivery. This pragmatic randomised controlled trial will investigate whether an Internet-delivered intervention that combines PCST and physiotherapist-guided exercise (PCST + Ex) is more effective than online educational material (educational control) in people with persistent knee pain. METHODS/DESIGN: We will recruit 148 people over 50 years of age with self-reported persistent knee pain consistent with knee OA from the Australian community. Following completion of baseline questionnaires, participants will be randomly allocated to access a 3-month intervention of either (i) online educational material, or (ii) the same online material plus an 8-module (once per week) Internet-based PCST program and seven Internet-delivered physiotherapy sessions with a home exercise programs to be performed 3 times per week. Outcomes will be measured at baseline, 3 months and 9 months with the primary time point at 3 months. Primary outcomes are average knee pain on walking (11-point numeric rating scale) and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index subscale). Secondary outcomes include additional measures of knee pain, health-related quality-of life, perceived global change in symptoms, and potential moderators and mediators of outcomes including self-efficacy for pain management and function, pain coping attempts and pain catastrophising. Other measures of adherence, adverse events, harms, use of health services/co-interventions, and process measures including appropriateness and satisfaction of the intervention, will be collected at 3, 6 and 9 months. DISCUSSION: The findings will help determine the effectiveness and acceptability of Internet access to a combination of interventions that are known to be beneficial to people with persistent knee pain. This study has the potential to guide clinical practice towards innovative modes of healthcare provision. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry reference: ACTRN12614000243617. PMID- 25125071 TI - Posterior sclera reinforcement and phakic intraocular lens implantation for highly myopic amblyopia in children: a 3-year follow-up. AB - PURPOSE: To study the safety and efficacy of posterior scleral reinforcement (PSR) combined with phakic intraocular lens (PIOLs) implantation for highly myopic amblyopia in children. METHODS: This study included eight highly myopic children (11 eyes) who failed in conventional therapy for amblyopia using various combination of spectacles, contact lenses, and intensive patching before enrollment into this study. They were treated sequentially with PSR and PIOL implantation, and were followed up for 3 years after surgery. Uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) in LogMAR, spherical equivalent power (SE), and complications were evaluated. RESULTS: Before surgery, the mean UCVA was 1.59+/-0.33, BCVA, 0.74+/-0.37, SE, -17.57+/-5.56D, the axial length (AL), 30.09+/-2.18 mm. After PSR, BCVA improved one line in three patients, the rest were unchanged, and AL was unchanged among all cases. Six eyes of three patients were implanted with an iris-claw PIOL and five eyes of five patients were implanted with a posterior PIOL. After completion of treatment, the mean UCVA was 0.44+/-0.21, BCVA 0.38+/-0.24, SE -0.54+/-0.74 D, and AL 30.35+/ 2.29 mm. No patient experienced complications. CONCLUSION: Combined PSR and PIOL implantation treatment for highly myopic amblyopia in children is safe and effective. PMID- 25125070 TI - Prevalence of glaucoma in patients with moderate to severe obstructive sleep apnea: ocular morbidity and outcomes in a 3 year follow-up study. AB - PURPOSE: This study was conducted to investigate the prevalence and progression of glaucoma in patients receiving treatment for obstructive sleep apnea (OSA). We also investigated whether there is an association between severity of OSA and the incidence of glaucoma. METHODS: A total of 39 patients aged >30 years who had been diagnosed with moderate and severe OSA in the sleep clinic at Hamad General Hospital were assessed for the presence of glaucoma. The severity of OSA was graded as mild, moderate, or severe based on American Association of Sleep Medicine (AASM) criteria using the apnea hypopnea index. Before enrollment, all patients underwent a complete ophthalmic examination including serial visual field tests, optical coherence tomography (OCT) with fundus photographs, and pachymetry. Enrolled patients were followed up in the ophthalmology outpatient clinic and sleep clinic for a period of 3 years. RESULTS: Examinations found that 8 (20.5%; 95% confidence interval (CI) 9.9-37%) of the 39 patients with OSA had glaucoma. Six (75%; 95% CI 36-96%) of these patients had normal-tension glaucoma (NTG) and two (25%; 95% CI 4.5-64.4%) patients had high-tension glaucoma. Among the 27 patients with severe OSA, 7 (25.9%; 95% CI 8-34%) had glaucoma, and among 12 patients with moderate OSA, 1 (8.3%; 95% CI 0.1-15%) had glaucoma. During the course of follow-up, two patients who previously did not have glaucoma were reclassified as NTG and two patients with glaucoma deteriorated. A higher prevalence of glaucoma in the severe OSA group compared with the moderate OSA group was found, albeit a statistically significant difference could not be attained (P=0.4). CONCLUSIONS: Our study showed that severe OSA is an important risk factor for developing glaucoma. Adequate treatment of OSA, along with optimal ophthalmic care, resulted in better control of glaucoma. PMID- 25125073 TI - Combinatorial gene therapy accelerates bone regeneration: non-viral dual delivery of VEGF and BMP2 in a collagen-nanohydroxyapatite scaffold. AB - Vascularization and bone repair are accelerated by a series of gene-activated scaffolds delivering both an angiogenic and an osteogenic gene. Stem cell mediated osteogenesis in vitro, in addition to increased vascularization and bone repair by host cells in vivo, is enhanced using all systems while the use of the nanohydroxyapatite vector to deliver both genes markedly enhances bone healing. PMID- 25125074 TI - Johann Vesling (1598-1649): seventeenth century anatomist of Padua and his Syntagma Anatomicum. AB - Johann Vesling (1598-1649) was a German anatomist and surgeon who belonged to the golden period of the illustrious University of Padua. He made significant contributions to the advancement of anatomical knowledge during the 17th century and is remembered most for his remarkable anatomical work, the Syntagma Anatomicum, which was published in 1641. He was the first to describe the soleus muscle and to emphasize its resemblance to the sole fish. He produced the earliest illustrations of the human lymphatic system and was one of the first to document observations about the thoracic duct. He was also the first to report the bifurcation of the human hepatic portal vein on entering the fissure of the liver. His observations from embryological experiments were critical for understanding the development of the four-chambered heart. He was one of the first authors to state that four pulmonary veins empty into the left atrium of the heart. Syntagma Anatomicum (1641) was the most widely used anatomical text in Europe for almost a century and was republished a number of times with editions in Latin, German, Dutch, and English. Syntagma was the first illustrated western anatomical text to reach Japan and laid the foundation for the development of European medicine there. The illustrations used in it deviated from the artistic convention that had characterized anatomical figures from the time of Vesalius, and focused instead on representing anatomical details to make them helpful for medicine and surgery. Clin. Anat. 27:1122-1127, 2014. (c) 2014 Wiley Periodicals, Inc. PMID- 25125072 TI - Optical quality of the diabetic eye: a review. AB - Diabetes mellitus is a metabolic disorder characterized by the presence of chronic hyperglycaemia. Several structural, morphological, and physiological changes in each of ocular component have been described in detail during the past decades. Due to these abnormalities, the diabetic patient undergoes a degradation of the retinal image by an increase of higher ocular aberrations and ocular scattering coming from mainly tear film, cornea, and crystalline lens. This review aims to provide an overview of current knowledge about the effects of diabetes mellitus in these optical phenomena and its consequence on the visual quality of the diabetic patient. PMID- 25125075 TI - Prevalence of and risk factors for diabetic macular edema in the United States. AB - IMPORTANCE: Diabetic macular edema (DME) is a leading cause of vision loss in persons with diabetes mellitus. Although there are national estimates for the prevalence of diabetic retinopathy and its risk factors among persons with diabetes, to our knowledge, no comparable estimates are available for DME specifically. OBJECTIVES: To estimate the prevalence of DME in the US population and to identify associated risk factors. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis of 1038 participants aged 40 years or older with diabetes and valid fundus photographs in the 2005 to 2008 National Health and Nutrition Examination Survey. MAIN OUTCOMES AND MEASURES: The overall prevalence of DME and its prevalence according to age, race/ethnicity, and sex. RESULTS: Of the 1038 persons with diabetes analyzed for this study, 55 had DME, for an overall weighted prevalence of 3.8% (95% CI, 2.7%-4.9%) or approximately 746, 000 persons in the US 2010 population aged 40 years or older. We identified no differences in the prevalence of DME by age or sex. Multivariable logistic regression analysis showed that the odds of having DME were higher for non Hispanic blacks than for non-Hispanic whites (odds ratio [OR], 2.64; 95% CI, 1.19 5.84; P = .02). Elevated levels of glycosylated hemoglobin A1c (OR, 1.47; 95% CI, 1.26-1.71 for each 1%; P < .001) and longer duration of diabetes (OR, 8.51; 95% CI, 3.70-19.54 for >= 10 vs <10 years; P < .001) were also associated with DME prevalence. CONCLUSIONS AND RELEVANCE: These results suggest a greater burden of DME among non-Hispanic blacks, individuals with high levels of hemoglobin A1c, and those with longer duration of diabetes. Given recent treatment advances in reducing vision loss and preserving vision in persons with DME, it is imperative that all persons with diabetes receive early screening; this recommendation is even more important for those at higher risk for DME. PMID- 25125076 TI - Use of three-dimensional time-resolved phase-contrast magnetic resonance imaging with vastly undersampled isotropic projection reconstruction to assess renal blood flow in a renal cell carcinoma patient treated with sunitinib: a case report. AB - BACKGROUND: New imaging modalities to assess the efficacy of drugs that have molecular targets remain under development. Here, we describe for the first time the use of time-resolved three-dimensional phase-contrast magnetic resonance imaging to monitor changes in blood supply to a tumor during sunitinib treatment in a patient with localized renal cell carcinoma. CASE PRESENTATION: A 43-year old Japanese woman with a tumor-bearing but functional single kidney presented at our hospital in July 2012. Computed tomography and magnetic resonance imaging revealed a cT1aN0M0 renal cell carcinoma embedded in the upper central region of the left kidney. She was prescribed sunitinib as neoadjuvant therapy for 8 months, and then underwent partial nephrectomy. Tumor monitoring during this time was done using time-resolved three-dimensional phase-contrast magnetic resonance imaging, a recent technique which specifically measures blood flow in the various vessels of the kidney. This imaging allowed visualization of the redistribution of renal blood flow during treatment, and showed that flow to the tumor was decreased and flows to other areas increased. Of note, this change occurred in the absence of any change in tumor size. CONCLUSION: The ability of time-resolved three-dimensional phase-contrast magnetic resonance imaging to provide quantitative information on blood supply to tumors may be useful in monitoring the efficacy of sunitinib treatment. PMID- 25125077 TI - Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e., fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. In a cohort study, data from 229 well characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (+/-5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. NAFLD patients had an increased mortality compared with the reference population (hazard ratio [HR] 1.29, confidence interval [CI] 1.04-1.59, P = 0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, P = 0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, P = 0.001), infectious disease (HR 2.71, CI 1.02-7.26, P = 0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, P = 0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, P = 0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, P < 0.001). CONCLUSION: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality. PMID- 25125078 TI - PTEN regulates plasma membrane expression of glucose transporter 1 and glucose uptake in thyroid cancer cells. AB - Glucose represents an important source of energy for the cells. Proliferating cancer cells consume elevated quantity of glucose, which is converted into lactate regardless of the presence of oxygen. This phenomenon, known as the Warburg effect, has been proven to be useful for imaging metabolically active tumours in cancer patients by (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glucose is internalised in the cells by glucose transporters (GLUTs) belonging to the GLUT family. GLUT1 (SLC2A1) is the most prevalent isoform in more aggressive and less differentiated thyroid cancer histotypes. In a previous work, we found that loss of expression of PTEN was associated with increased expression of GLUT1 on the plasma membrane (PM) and probability of detecting thyroid incidentalomas by FDG-PET. Herein, we investigated the molecular pathways that govern the expression of GLUT1 on the PM and the glucose uptake in WRO (expressing WT PTEN) and FTC133 (PTEN null) follicular thyroid cancer cells cultured under glucose-depleted conditions. The membrane expression of GLUT1 was enhanced in glucose-deprived cells. Through genetic manipulations of PTEN expression, we could demonstrate that the lack of this oncosuppressor has a dominant effect on the membrane expression of GLUT1 and glucose uptake. We conclude that loss of function of PTEN increases the probability of cancer detection by FDG-PET or other glucose-based imaging diagnosis. PMID- 25125080 TI - Recent advances in the discovery of N-myristoyltransferase inhibitors. AB - N-Myristoyltransferase (NMT) is a cytosolic monomeric enzyme present in eukaryotes such as fungi and protozoa, but is not found in prokaryotes. The attachment of a 14-carbon saturated fatty acid, myristate, from myristoyl-CoA (14:0 CoA) to the N-terminal glycine residue in a specific set of cellular proteins is commonly called protein N-myristoylation. The myristoylation reaction catalyzed by the enzyme myristoyl CoA:NMT is both necessary for the growth of various organisms and conclusive for cellular proliferation. Therefore, NMT has been identified as a novel and promising target for antifungal, antiparasitic, and anticancer agents, and a large number of potent NMT inhibitors with antifungal, antiparasitic, and anticancer activities have been reported. Herein we describe recent advances in the discovery of NMT inhibitors. We introduce not only the functions of NMT, but also some representative natural and synthetic inhibitors, with a focus on their biological activity, selectivity, and structure activity relationship (SAR) information. In particular, inspiration from NMT inhibitor structures and the future direction of these compounds are highlighted. PMID- 25125081 TI - Requests for dermatology specialist consultations show an inverse correlation with waiting time: an analysis of waiting time to access dermatology specialist health care in Bolzano, South Tyrol, Italy. PMID- 25125079 TI - Clopidogrel discontinuation within the first year after coronary drug-eluting stent implantation: an observational study. AB - BACKGROUND: The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available. METHODS: We followed 4,154 patients treated with coronary drug-eluting stents in Western Denmark for 1 year and obtained data on redeemed clopidogrel prescriptions and major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, or stent thrombosis) from medical databases. RESULTS: Discontinuation of clopidogrel within the first 3 months after stent implantation was associated with a significantly increased rate of MACE at 1-year follow-up (hazard ratio (HR) 2.06; 95% confidence interval (CI): 1.08-3.93). Discontinuation 3-6 months (HR 1.29; 95% CI: 0.70-2.41) and 6-12 months (HR 1.29; 95% CI: 0.54-3.07) after stent implantation were associated with smaller, not statistically significant, increases in MACE rates. Among patients who discontinued clopidogrel, MACE rates were highest within the first 2 months after discontinuation. CONCLUSIONS: Discontinuation of clopidogrel was associated with an increased rate of MACE among patients treated with drug-eluting stents. The increase was statistically significant within the first 3 months after drug eluting stent implantation but not after 3 to 12 months. PMID- 25125084 TI - Physiological flexibility in an avian range expansion. AB - The mechanisms that enable animals to colonize new areas are little known, but growing evidence indicates that the regulation of stress hormones is important. Stress hormones probably influence invasions because they enable organisms to adjust their phenotypes depending on environmental context. Often, studies of stress hormones are based on single or a few samples from individuals even though the flexibility in the regulation of such hormones is what enables them to achieve homeostasis and facilitate performance. Here, we asked whether flexibility in the regulation of one stress hormone, corticosterone, was related to colonization success in one of the world's most successful avian invaders, the house sparrow (Passer domesticus). We studied Kenyan house sparrows, as the species was recently introduced there (around 1950) and has since expanded northwestward. Previous work in this system revealed that younger populations released more corticosterone during a restraint stressor than older populations. Our first goal was to discern whether such population differences were fixed or flexible in adulthood; our second goal was to determine whether individual identity explained any variation in corticosterone regulation. As before, we found that corticosterone responses to short-term restraint (i.e., stress responses), but not baseline corticosterone, were larger in younger populations. We also found that both baseline and stress-induced corticosterone measures were flexible; both metrics became similar among sites after one week of captivity. For stress responses, we also found that individual identity was important. Altogether, the present data suggest that the colonization of Kenya by house sparrows might have been facilitated by stress hormone regulatory flexibility. PMID- 25125083 TI - Neuroendocrine gene expression reveals a decrease in dopamine D2B receptor with no changes in GnRH system during prepubertal metamorphosis of silvering in wild Japanese eel. AB - Silvering is a prepubertal metamorphosis preparing the eel to the oceanic reproductive migration. A moderate gonad development occurs during this metamorphosis from the sedentary yellow stage to the migratory silver stage. The aim of this study was to elucidate the molecular aspects of various endocrine parameters of BPG axis at different ovarian developmental stages in wild yellow and silver female Japanese eels. The GSI of the sampled female eels ranged between 0.18 and 2.3%, corresponding to yellow, pre-silver and silver stages. Gonad histology showed changes from previtellogenic oocytes in yellow eels to early vitellogenic oocytes in silver eels. Both serum E2 and T concentrations significantly increased with ovarian development indicating a significant activation of steroidogenesis during silvering. In agreement with previous studies, significant increases in pituitary gonadotropin beta subunits FSH-beta and LH-beta transcripts were also measured by qPCR, supporting that the activation of pituitary gonadotropin expression is likely responsible for the significant ovarian development observed during silvering. We investigated for the first time the possible brain neuroendocrine mechanisms involved in the activation of the pituitary gonadotropic function during silvering. By analyzing the expression of genes representative of the stimulatory GnRH control and the inhibitory dopaminergic control. The transcript levels of mGnRH and the three GnRH receptors did not change in the brain and pituitary between yellow and silver stages, suggesting that gene expression of the GnRH system is not significantly activated during silvering. The brain transcript levels of tyrosine hydroxylase, limiting enzyme of DA synthesis did not change during silvering, indicating that the DA synthesis activity was maintained. In contrast, a significant decrease in DA-D2B receptor expression in the forebrain and pituitary was observed, with no changes in DA-D2A receptor. The decrease in the pituitary expression of DA-D2BR during silvering would allow a reduced inhibitory effect of DA. We may raise the hypothesis that this regulation of D2BR gene expression is one of the neuroendocrine mechanisms involved in the slight activation of the pituitary gonadotropin and gonadal activity that occur at silvering. PMID- 25125085 TI - Impact of platelet transfusion on toxicity and mortality after hematopoietic progenitor cell transplantation. AB - BACKGROUND: Thrombocytopenia occurs commonly after hematopoietic progenitor cell transplantation (HPCT) and is associated with potential morbidity and mortality. Few studies have examined the impact of platelet (PLT) transfusion on clinical outcomes in HPCT while optimal PLT transfusion strategies after HSCT remain uncertain. STUDY DESIGN AND METHODS: A retrospective single-center cohort study was conducted on 522 patients undergoing HPCT between January 2002 and December 2007. Associations between PLT transfusion events and clinical characteristics with transplant-related outcomes were assessed using univariate and multivariate analysis. RESULTS: Mean number of PLT transfusion events before Day +60 posttransplant was 7.5 (95% confidence interval, 6.7-8.4) with greater number of events after allogeneic compared with autologous HPCT (p < 0.01). Univariate and multivariate analysis confirmed that the number of PLT transfusion events was associated with increased 100-day nonrelapse mortality (p < 0.01), posttransplant length of hospital stay (p < 0.01), need for intensive care unit admission (p < 0.01), and number of organs affected by severe toxicity (p < 0.01). CONCLUSION: HPCT-related toxicity and mortality are associated with increased PLT transfusion events. Alternative strategies to reduce PLT transfusions after HPCT may warrant future study. PMID- 25125082 TI - Metabolic stressors and signals differentially affect energy allocation between reproduction and immune function. AB - Most free-living animals have finite energy stores that they must allocate to different physiological and behavioral processes. In times of energetic stress, trade-offs in energy allocation among these processes may occur. The manifestation of trade-offs may depend on the source (e.g., glucose, lipids) and severity of energy limitation. In this study, we investigated energetic trade offs between the reproductive and immune systems by experimentally limiting energy availability to female Siberian hamsters (Phodopus sungorus) with 2-deoxy d-glucose, a compound that disrupts cellular utilization of glucose. We observed how glucoprivation at two levels of severity affected allocation to reproduction and immunity. Additionally, we treated a subset of these hamsters with leptin, an adipose hormone that provides a direct signal of available fat stores, in order to determine how increasing this signal of fat stores influences glucoprivation induced trade-offs. We observed trade-offs between the reproductive and immune systems and that these trade-offs depended on the severity of energy limitation and exogenous leptin signaling. The majority of the animals experiencing mild glucoprivation entered anestrus, whereas leptin treatment restored estrous cycling in these animals. Surprisingly, virtually all animals experiencing more severe glucoprivation maintained normal estrous cycling throughout the experiment; however, exogenous leptin resulted in lower antibody production in this group. These data suggest that variation in these trade-offs may be mediated by shifts between glucose and fatty acid utilization. Collectively, the results of the present study highlight the context-dependent nature of these trade-offs, as trade-offs induced by the same metabolic stressor can manifest differently depending on its intensity. PMID- 25125086 TI - Manganese-mediated intermolecular arylation of H-phosphinates and related compounds. AB - The intermolecular radical functionalization of arenes with aryl and alkyl H phosphinate esters, as well as diphenylphosphine oxide and H-phosphonate diesters, is described. The novel catalytic Mn(II) /excess Mn(IV) system is a convenient and inexpensive solution to directly convert Csp2 ?H into C?P bonds. The reaction can be employed to functionalize P-stereogenic H-phosphinates since it is stereospecific. With monosubstituted aromatics, the selectivity for para substitution increases in the order (RO)2 P(O)H=30 LPD) and smaller (<=29 LPD) series. Pathology demonstrated ductal adenocarcinoma in 30.6 % of the specimens, other malignant tumors in 51.7 %, and benign tumor/disease in 17.5 %. The mean number of lymph nodes examined was 14.4 (7-32), and the rate of microscopically positive tumor margin was 4.4 %. CONCLUSIONS: In selected patients, operated on by expert laparoscopic pancreatic surgeons, LPD is feasible and safe. PMID- 25125093 TI - Incidence and risk factors of incisional hernia formation following abdominal organ transplantation. AB - BACKGROUND: Hernia formation is common following abdominal operations, and transplant patients are at increased risk due to postoperative immunosuppression. The purpose of this study was to estimate the incidence of incisional hernia formation following primary abdominal solid organ transplantation and identify clinical risk factors for hernia formation. METHODS: We performed a single institution retrospective review of a prospectively collected database to evaluate all patients who underwent primary liver, kidney, or pancreas transplantation between 2000 and 2011. The primary outcome was hernia formation at the transplant incision. Univariate and multivariate Cox proportional hazards models were used to identify risk factors for incisional hernia formation. RESULTS: A total of 3,460 transplants were performed during the study period: 2,247 kidney only, 718 liver only, and 495 pancreas or simultaneous pancreas and kidney (pancreas group). The overall incisional hernia rate was 7.5 %. The Kaplan Meier rates of hernia formation at 1, 5, and 10 years were 2.5, 4.9, and 7.0 % for kidney; 4.5, 13.6, and 19.0 % for liver; and 2.5, 12.7, and 21.8 % for the pancreas groups. On univariate analysis, surgical site infection (SSI), body mass index (BMI) >25, delayed graft function, and withholding a calcineurin inhibitor or mycophenolate mofetil (MMF) were associated with hernia formation in the kidney group. SSI and BMI >25 were associated with hernia formation in the liver group. In the pancreas group, SSI, cyclosporine, and withholding MMF were all associated with hernia formation. On multivariate analysis, SSI was strongly associated with hernia formation in all groups. Hazard ratio: kidney = 24.71 (13.00-46.97); liver = 12.0 (6.40-22.52); pancreas = 12.95 (2.78-60.29). CONCLUSION: Incisional hernias are common following abdominal organ transplant with nearly one in five patients developing an incisional hernia 5 years after liver or pancreas transplantation. Strategies focusing on prevention and early treatment of SSI may help to decrease the risk of incisional hernia formation following abdominal organ transplantation. PMID- 25125094 TI - Differences in gaze behaviour of expert and junior surgeons performing open inguinal hernia repair. AB - INTRODUCTION: Various fields have used gaze behaviour to evaluate task proficiency. This may also apply to surgery for the assessment of technical skill, but has not previously been explored in live surgery. The aim was to assess differences in gaze behaviour between expert and junior surgeons during open inguinal hernia repair. METHODS: Gaze behaviour of expert and junior surgeons (defined by operative experience) performing the operation was recorded using eye-tracking glasses (SMI Eye Tracking Glasses 2.0, SensoMotoric Instruments, Germany). Primary endpoints were fixation frequency (steady eye gaze rate) and dwell time (fixation and saccades duration) and were analysed for designated areas of interest in the subject's visual field. Secondary endpoints were maximum pupil size, pupil rate of change (change frequency in pupil size) and pupil entropy (predictability of pupil change). NASA TLX scale measured perceived workload. Recorded metrics were compared between groups for the entire procedure and for comparable procedural segments. RESULTS: Twenty-five cases were recorded, with 13 operations analysed, from 9 surgeons giving 630 min of data, recorded at 30 Hz. Experts demonstrated higher fixation frequency (median[IQR] 1.86 [0.3] vs 0.96 [0.3]; P = 0.006) and dwell time on the operative site during application of mesh (792 [159] vs 469 [109] s; P = 0.028), closure of the external oblique (1.79 [0.2] vs 1.20 [0.6]; P = 0.003) (625 [154] vs 448 [147] s; P = 0.032) and dwelled more on the sterile field during cutting of mesh (716 [173] vs 268 [297] s; P = 0.019). NASA TLX scores indicated experts found the procedure less mentally demanding than juniors (3 [2] vs 12 [5.2]; P = 0.038). No subjects reported problems with wearing of the device, or obstruction of view. CONCLUSION: Use of portable eye-tracking technology in open surgery is feasible, without impinging surgical performance. Differences in gaze behaviour during open inguinal hernia repair can be seen between expert and junior surgeons and may have uses for assessment of surgical skill. PMID- 25125095 TI - A comparative study of survival after minimally invasive and open oesophagectomy. AB - BACKGROUND: Oesophageal cancer is increasing in incidence worldwide. Minimally invasive techniques have been used to perform oesophagectomy, but concerns regarding these techniques remain. Since its description by Cuschieri in 1992, the use of minimally invasive oesophagectomy (MIO) has increased, but still only used in a minority of resections in the UK in 2009. In particular, there has been reluctance to use minimally invasive (thoracoscopic and laparoscopic) techniques in more advanced cancers for fears regarding the adequacy of the oncological resection. In order to identify any factors that could affect survival, we undertook a retrospective analysis on all patients who underwent surgery in our department over an 8-year period. METHODS: A retrospective data analysis was undertaken on all patients who underwent oesophagectomy in a tertiary upper gastrointestinal surgery unit, from 2005 to 2012 inclusive. Data were collected from the departmental database and case note review, with follow-up and survival data to time of data collection. The survival data were analysed using univariate and multivariate Cox proportional hazard regression models to determine which variables affected survival. Variables examined included age, tumour position, tumour stage (T0, 1, 2 vs T3, 4), nodal stage (N0 vs N1), tumour histology, completeness of resection (R0 vs R1), use of neoadjuvant chemotherapy and operative technique (thoracoscopic/laparoscopic (MIO) vs laparoscopic abdomen/open chest (Lap assisted) vs Open. RESULTS: 334 patients underwent oesophagectomy between 2005 and 2012. Male to female ratio was 3.75:1, with a mean age of 64 years (range 36-87). There were 83 open oesophagectomies, 187 laparoscopically assisted oesophagectomies and 64 minimally invasive oesophagectomies. Following univariate regression analysis the following factors were found to be correlated to survival: use of neoadjuvant chemotherapy (Hazard Ratio 2.889, 95 % CI 1.737-4.806), T stage 3 or 4 (3.749, 2.475-5.72), Node positive (5.225, 3.561-7.665), R1 resection (2.182, 1.425-3.341), type of operation (MIO compared to open oesophagectomy) (0.293, 0.158-0.541). There was no significant relationship between age, tumour position or tumour histology and length of survival. When these factors were entered into a multivariate model, the independently significant factors correlated to survival were found to be T stage 3 or 4 (HR 1.969, 1.248-3.105), Node positive (3.833, 2.548-5.766) and type of operation (MIO compared to open) (0.5186, 0.277-0.972). CONCLUSION: Multiple small studies have found reduced pulmonary complication rates and duration of hospital stay when using a minimally invasive approach compared to open. Concerns in the literature over long-term outcomes, however, have led to limited utilisation of this method, especially in advanced disease. The data from this large study show significantly better survival following operations performed using minimally invasive techniques compared to open, however, we have not adjusted for some known or unknown confounding factors. International and national RCTs, however, will provide more information in due course. PMID- 25125096 TI - Laparoscopy in the diagnosis and repair of diaphragmatic injuries in left-sided penetrating thoracoabdominal trauma: laparoscopy in trauma. AB - BACKGROUND: Diaphragmatic injuries from penetrating thoracoabdominal trauma are notoriously difficult to detect with clinical and radiological evaluation. The aim of this study was to establish the incidence of diaphragmatic injury from penetrating thoracoabdominal trauma, clinical and radiological features predictive of a diaphragmatic injury and the feasibility of laparoscopic repair. METHODS: This is a prospective consecutive case series conducted in a metropolitan hospital complex. Fifty five patients were enrolled into the study and underwent a standardized laparoscopic procedure. Only stable patients were selected and right-sided penetrating thoracoabdominal injuries were excluded. The patients' clinical details, radiological findings, operative procedure, treatment of the diaphragmatic injury and complications were collected and analysed. RESULTS: There were a total of 55 patients, of whom, 22 (40 %) had diaphragmatic injuries. The mean age was 26.3 +/- 7.8 years (range 15-44) with a male:female ratio of 10:1. The causes of injury were stab in 54 (98.2 %) patients and firearm in one (1.8 %). Twenty six (47.3 %) patients had positive radiological findings, of which 10 (38.5 %) had a diaphragmatic injury. There were 6 (27.3 %) associated intra-abdominal injuries. Twenty one (95.5 %) of 22 patients with diaphragmatic injuries were successfully repaired laparoscopically. Mean duration of procedure with diaphragmatic repair was 74.9 +/- 22.5 min compared to 38.3 +/- 16.9 min without diaphragmatic repair. Six patients (10.9 %) had minor intra-operative complications. There were no deaths. Hospital stay was 2.9 +/- 3.4 days. CONCLUSIONS: Diaphragmatic injury was present in 40 % of patients with left-sided thoracoabdominal injury. Radiological findings were not reliable in predicting diaphragmatic injury. The majority of these injuries can be safely repaired laparoscopically. PMID- 25125097 TI - Neuromuscular blockade improves surgical conditions (NISCO). AB - BACKGROUND: We examined the impact of muscle relaxation on surgical conditions and patients' postoperative outcome during elective laparoscopic cholecystectomy under balanced anaesthesia. METHODS: After approval and consent, 57 anaesthetized patients were randomly assigned to group no neuromuscular blockade (No NMB) and deep neuromuscular blockade (Deep NMB), i.e. no twitch response to train-of-four nerve stimulation. Laparoscopic cholecystectomy was performed using the 4-trocar technique with a CO2-pneumoperitoneum. Surgical conditions were assessed using a Visual Analogue Scale. Movement of diaphragm or abdominal muscles, inadequate visibility, or breathing and coughing against the ventilator were documented as events reflecting inadequate muscle relaxation. Independently, surgeons could request 0.3 mg/kg rocuronium to improve surgical conditions. Workflow variables were obtained as a surrogate of surgical conditions. Data are presented as mean (95 % confidence interval). The trial is registered at ClinicalTrials.gov (NCT00895778). RESULTS: While in 12 of 25 patients of group "No NMB" one or more adverse events impaired the surgical procedure (p < 0.001), only 1 of 25 patients of group "Deep NMB" showed an adverse event. Deep NMB resulted in an absolute risk reduction of 0.44 (0.23-0.65) and a number needed to treat of 2.3 (1.5-4.4), respectively. Surgeons requested 0.3 mg/kg rocuronium in 10 of 25 cases (40 %) of group "No NMB" only. This dose significantly improved surgical conditions by an average 62 of 100 possible points. All further variables did not differ between groups. CONCLUSIONS: Deep NMB ameliorates surgical conditions for laparoscopic cholecystectomy by improved visibility and reduction of involuntary movements. PMID- 25125098 TI - The efficacy of prophylactic IVC filters in gastric bypass surgery. AB - BACKGROUND: Patients undergoing gastric bypass surgery have a high risk for thromboembolic events. Over the last decade, the use of prophylactic IVC filters (IVCF) has drastically increased for patients who are considered high risk. However, the role and efficacy of prophylactic IVCF placement remain controversial, and the literature is limited to a few retrospective studies. METHODS: We conducted a systematic review of the literature. A total of 21 articles were analyzed, and eight relevant retrospective studies were chosen for review of data. Data from laparoscopic gastric bypass surgery were compared to open gastric bypass surgery RESULTS: The relevant eight retrospective studies included a total of 597 patients. Patients had IVCFs before laparoscopic gastric bypass (41 %) and before open gastric bypass (59 %). There were 5 postoperative pulmonary emboli (PE) (0.84 %), 21 DVTs (3.52 %), 5 minor IVCF-related complications (0.84 %), 2 major IVCF-related complications (0.34 %), and 10 deaths (1.68 %). The rate of postoperative PE was the same in the laparoscopic group and the open group (0.84 %). The rate of DVT in the laparoscopic group was 5.02 %, and in the open group, it was 2.23 %. CONCLUSION: It is estimated that 55 % of bariatric surgeons use IVCF in high-risk patients. Prospective research that supports the use of IVCF is very limited, and individualized placement relies on retrospective studies only. In addition, patient characteristics associated with high risk vary between different studies. Our review showed that most of the published studies support the use of prophylactic IVCF and found it to be safe. On the other hand, the largest and most recent retrospective cohort study does not support their use. The efficacy of prophylactic IVCFs before gastric bypass surgery in high-risk patients has not been established. PMID- 25125099 TI - Comparative analysis of the functionality of simulators of the da Vinci surgical robot. AB - BACKGROUND: The implementation of robotic technology in minimally invasive surgery has led to the need to develop more efficient and effective training methods, as well as assessment and skill maintenance tools for surgical education. Multiple simulators and procedures are available for educational and training purposes. A need for comparative evaluations of these simulators exists to aid users in selecting an appropriate device for their purposes. METHODS: We conducted an objective review and comparison of the design and capabilities of all dedicated simulators of the da Vinci robot, the da Vinci Skill Simulator (DVSS) (Intuitive Surgical Inc., Sunnyvale, CA, USA), dV-Trainer (dVT) (Mimic Technologies Inc., Seattle, WA, USA), and Robotic Surgery Simulator (RoSS) (Simulated Surgical Skills, LLC, Williamsville, NY, USA). This provides base specifications of the hardware and software, with an emphasis on the training capabilities of each system. RESULTS: Each simulator contains a large number of training exercises, DVSS = 40, dVT = 65, and RoSS = 52 for skills development. All three offer 3D visual images but use different display technologies. The DVSS leverages the real robotic surgeon's console to provide visualization, hand controls, and foot pedals. The dVT and RoSS created simulated versions of all of these control systems. They include systems management services which allow instructors to collect, export, and analyze the scores of students using the simulators. CONCLUSIONS: This study is the first to provide comparative information of the three simulators functional capabilities with an emphasis on their educational skills. They offer unique advantages and capabilities in training robotic surgeons. Each device has been the subject of multiple validation experiments which have been published in the literature. But those do not provide specific details on the capabilities of the simulators which are necessary for an understanding sufficient to select the one best suited for an organization's needs. PMID- 25125100 TI - Transoral periosteal thyroidectomy: cadaver to human. AB - BACKGROUND: Although endoscopic thyroid surgery is gaining wide acceptance, existing endoscopic methods for thyroidectomy are blamed for the increased frequency of flap dissections and longer surgical times. More recently, transoral endoscopic thyroidectomy has overcome the limitations of previous approaches. Herein, we present our initial experience with transoral periosteal thyroidectomy (TOPOT) in cadaver and porcine models. Using these models, the surgical view was improved and had greater freedom of motion; the technique was then performed in human subjects using robotic TOPOT, which has not previously been reported. METHOD: TOPOTs were performed in seven fresh human cadavers and ten live pigs. Total thyroidectomies were performed in all cadavers and pigs. After the cadaver and animal trials, four human patients underwent robotic TOPOT performed using the da Vinci(r) surgical system at Korea University Anam Hospital. Recurrent laryngeal nerve function, intra- and postoperative complications, and postoperative outcomes were assessed in all patients. RESULT: One left lobectomy for follicular adenoma, two right lobectomies for nodular hyperplasia, and one left lobectomy with a central neck dissection for papillary thyroid microcarcinoma were performed in the human subjects using a robotic transoral periosteal approach. In three cases, paresthesia occurred in the mental nerve, but this improved within 4 weeks in all cases. No local infections occurred at the incision site or anterior neck, and no recurrent laryngeal nerve cord palsies occurred postoperatively. CONCLUSION: TOPOT may be an effective and safe approach for robotic thyroid surgery. PMID- 25125101 TI - Laparoscopic Roux-en-Y gastric bypass in the elderly: feasibility, short-term safety, and impact on comorbidity and weight in 250 cases. AB - INTRODUCTION: In the elderly obese population, frequently suffering from multiple comorbidities, laparoscopic Roux-en-Y gastric bypass (LRYGB) is considered a high risk procedure. The aim of this study was to evaluate short-term safety (30-day hospital morbidity and mortality) of this procedure and its impact on weight and associated comorbidities in the medium term (type-two diabetes, hypertension, sleep apnea, hypercholesterolemia, and joint pain). METHODS: This study represents a retrospective analysis of all our Belgian patients older than 60 years of age who underwent a LRYGB between October 2004 and October 2012. Patient files were reviewed and patients were contacted by formal consultation or by phone for an update of their clinical status. Demographics, operative details, postoperative course, and the evolution of weight and associated comorbidities were registered. RESULTS: A total of 280 patients were included. A complete follow-up was available for 250 patients (89 %), of whom 161 were female and 89 male. Mean age, BMI, and hospital stay were 64.1 years (60-78 years), 41.9 kg/m(2) (27.4-68 kg/m(2)), and 4.3 days (2-19 days), respectively. There was no in-hospital mortality, 27 (10.8 %) patients suffered from early postoperative complications and 5 (2 %) patients needed to be readmitted. After a mean follow up of 31.5 months, the mean excess weight loss was 59.3 % (range 21.9-120.1 %). Resolution or improvement of diabetes, hypertension, sleep apnea, hypercholesterolemia, and joint pain was seen in 94.6, 77.6, 88.0, 77.1 and 57.6 % respectively. CONCLUSION: LRYGB has an acceptable complication rate in the elderly. Since all obesity-related comorbidities improved during follow-up, there is a plea not to exclude this subgroup of patients from the well-known benefits of gastric bypass surgery. PMID- 25125102 TI - Retention of fundamentals of laparoscopic surgery (FLS) proficiency with a biannual mandatory training session. AB - BACKGROUND: The fundamentals of laparoscopic surgery (FLS) program was developed by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) in 1997 with the goal of teaching surgeons the fundamental knowledge, judgment, and technical skills specific to laparoscopic surgery (Peters et al., Surgery JH 135:21-27, 2004; Soper et al., Bull Am College Surg NJ 93:30-32, 2008). This single academic institution observational study aimed to assess the effectiveness of a biannual FLS training curriculum on Post-Graduate Year [PGY] 1-5 proficiency levels, with a focus on one FLS task (PEG transfer). Previous studies have shown that obtaining expert FLS proficiency correlates with retaining proficiency in the future (Castellvi et al., Surgery 146:387-393, 2009). METHODS: PGY 1-5 residents (n = 28) at an academic general surgery residency program performed two timed PEG transfer tasks biannually. Participants were monitored by FLS certified examiners and standard FLS rules applied. Residents were expected to meet or exceed standards set by SAGES and FLS in consecutive timed PEG transfer trials (proficiency: <48 s). RESULTS: Twenty-eight residents participated (PGY 1-5). Participants showed proficiency if they completed the PEG transfer task in less than 48 s on two consecutive trials. None of the PGY 1 or PGY 2 residents completed two consecutive trials within the stated proficiency time, while the majority of the PGY 3-5 residents showed proficiency in the PEG transfer task. CONCLUSION: A biannual training session for FLS retains expert proficiency by PGY levels 4-5. Previous reports from our institution demonstrated that 95 % of the residents did not practice this task between mandatory biannual sessions. This suggests that, in combination with standard residency training, biannual FLS sessions confer retained expert skills by PGY 4-5. As the FLS exam is generally taken by PGY 4 and 5 residents and is required for board certification, general surgery residents that participate in biannual training sessions will likely retain expert proficiency and achieve FLS certification. PMID- 25125104 TI - Rotating ring-disk electrode with dual dynamic potential control: theory and practice. AB - Using the LabVIEWTM graphical programming language designed by National Instruments(r), a digital simulation model has been developed in order to describe electrochemical processes occurring at rotating ring-disk electrodes. The model allows for taking into consideration independent potential control of the two working electrodes, homogeneous electrode reactions, as well as spatial inhomogeneities of the working electrode surfaces. The main programming concepts, as well as the operation of the simulation software is presented. Several test simulations have been carried out in order to evaluate the accuracy of the calculations. PMID- 25125103 TI - Interactions of divalent calcium ions with head groups of zwitterionic phosphatidylcholine liposomal membranes. AB - The interaction of the divalent calcium ions with the zwitterionic lipid membranes was studied by measuring the lipid order parameter which is inversely proportional to the membrane fluidity. Small unilamellar lipid vesicles were prepared from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and then treated with different concentrations of divalent calcium ions. An increase in the order parameter and decrease in the fluidity of the liposomal membranes were observed after treatment with the calcium ions. The presence of positively charged iron oxide nanoparticles in the suspension of liposomes negligibly changed the results. The results of experiments were discussed theoretically within modified Langevin-Poisson-Boltzmann (MLPB) model leading to the conclusion that the membrane fluidity and ordering of the membrane lipids are primarily altered by the accumulation of calcium ions in the region of negatively charged phosphate groups within the head groups of the membrane lipids. PMID- 25125105 TI - Electrochemical reduction of perchlorate ions on ruthenium. AB - The reduction of perchlorate ions at ruthenium electrodes was investigated by voltammetry, chronoamperometry, impedance spectroscopy, and by measuring changes of interfacial stress changes using the cantilever bending method as functions of electrode potential, and concentrations of perchloric acid and HCl. The cyclic voltammograms recorded at a rotating (Ru) disc electrode were highly asymmetric with respect to the electrode potential axis, and a negative current could be observed even during the positive sweep. Chloride ions decrease the interfacial stress and exert an inhibiting effect on the reduction process indicating the role of competitive adsorption. The desorption rate of Cl(-) depends strongly on the hydrodynamic conditions, probably through desorption/diffusion coupling. These results serve as a warning that in perchlorate-containing solutions in contact with Ru the adsorption of chloride ions may also influence the rate of other electrochemical processes. PMID- 25125106 TI - Relative permittivity in stern and diffuse layers. AB - Stern layer and outer Helmholtz plane (i.e. the distance of closest approach) are considered within electric double layer models, where the orientational ordering of water dipoles is explicitly taken into account. It is shown that permittivity of the Stern layer is not independent of the surface charge density as it is frequently assumed in different theoretical models and simulations, but strongly depends on the magnitude of the surface charge density. Therefore, to predict the behaviour and realistic values of the surface potential and electric field, in the electrolyte solution near the charged surface, requires a surface charge density dependent permittivity of the Stern layer. PMID- 25125107 TI - Mechanism of electroreduction of the Henry reaction products. Electrochemically initiated degradation of 1-phenyl-2-nitroethanol. AB - Electroreduction of the Henry reaction product - i.e. 1-phenyl-2-nitroethanol (PNE) - in 0.1 M Bu(4)NClO(4) solution in MeCN has been investigated by a set of experimental (cyclic voltammetry, chronoamperometry, and controlled potential electrolysis) and theoretical (digital simulation and quantum chemical calculations) methods. The results obtained show that cathodically generated radical anion of PNE undergoes C-C bond cleavage reaction resulting in the formation of the free radical of benzyl alcohol and nitromethane anion. The proton transfer between these species affords nitromethane and benzaldehyde radical anion. Electron transfer from the last to PNE initiates the cyclic process of the PNE degradation. PMID- 25125108 TI - Permittivity spectroscopy - an insight into materials properties. AB - Permittivity Spectroscopy is a branch of the Impedance Spectroscopy specially tuned for measurements and analyses of dielectrics permittivity properties. The present paper presents experimental results on permittivity properties of composite objects in which a polarizable dielectric is distributed in a fine non polarizable matrix (solid or liquid) measured in frequency range 1 MHz down to 0.01 Hz. Two types of objects are studied - water in porous functional ceramics and lubricating oils. In both systems gigantic enhancement of the effective capacitance is observed. The first series of experiments was performed on porous membranes of yttrium doped barium cerate, which is a proton conducting ceramics with hydrophilic properties. At a given level of watering the measured capacitance is sharply increasing (3 to 5 orders of magnitude) in the lower frequency range. The second example covers permittivity study of lubricating oils, where the increase is 2-3 orders of magnitude. The phenomenon of gigantic enhancement of the effective capacitance could be related to a formation of dipole volume structures induced by the external alternating electrical field. PMID- 25125109 TI - Electrodeposition of Co/CoO nanoparticles onto graphene for ORR electrocatalysis: a study based on micro-X-ray absorption spectroscopy and X-ray fluorescence mapping. AB - Electrodeposition of graphene-supported Co for ORR electrocatalysts from an acetonitrile solution has been studied by a multi-technique approach, combining a suite of spectroscopic methods with electrochemical measurements, allowing a molecular-level understanding of potentiostatic and pulsed-potential plating processes from the organic solvent onto a freestanding graphene film. The formation of the graphene film by the light-scribe approach has been monitored by Raman spectroscopy; the electrodeposition process has been clarified by cyclic voltammetry and the compositional and chemical-state distribution of Co have been investigated ex situ by soft X-ray absorption spectroscopy and fluorescence mapping, showing that both spatial distribution and valence state are homogeneous and independent of the local current density. The deposit consists in micrometric aggregates of Co/CoO nanoparticles with diameter ca. 30 nm (pulsed) and 200 nm (potentiostatic deposition). Potentiostatic deposition allows to obtain better ORR electrocatalytic perfomance in terms of nnumber of transferred electrons, onset/ half-wave potential and current density. PMID- 25125110 TI - Some factors influencing power and energy capabilities of RuO2 supercapacitors. AB - Ruthenium oxide electrodes prepared by different routes were studied and the results discussed in terms of the possibility of using these electrodes in high power/high energy supercapacitors. The supercapacitor electrodes were prepared by mixing RuO(2) particles with a binder (Nafion((r)) or polyvinilydenfluoride) in various ratios. The results show that charging/discharging reaction of RuO(2) consists of at least two redox reactions taking place simultaneously at different rates. The contribution of each reaction in the overall process depends on the hydration of RuO(2) as well as on the type of binder and binder/RuO(2) ratio. From both energy and power capability of supercapacitors the best electrode composition would be hydrous RuO(2) with ~20% Nafion((r)) as a binder. Asymmetric supercapacitors assembled with RuO(2) and activated carbon as a counter electrode gave 26 and 12 W h kg(-1) at average specific power of 5 W g(-1) for RuO(2)/Nafion((r)) and RuO(2)/polyvinylidene fluoride, respectively. PMID- 25125111 TI - Stability of commercial Pt/C low temperature fuel cell catalyst: electrochemical IL-SEM study. AB - Platinum catalyst stability has been investigated under potentiostatic and potentiodynamic conditions with and without the presence of chloride anions. The combination of rotating disc electrode (RDE) and identical location scanning electron microscopy (IL-SEM) methods reveals that potentiodynamic degradation is much more severe compared to the potentiostatic and that chloride enhances platinum dissolution thus catalyst degradation. IL-SEM method nicely shows the platinum dissolution and redeposition on the top of a catalyst film. PMID- 25125112 TI - An innovative hybrid 3D analytic-numerical model for air breathing parallel channel counter-flow PEM fuel cells. AB - The parallel straight channel PEM fuel cell model presented in this paper extends the innovative hybrid 3D analytic-numerical (HAN) approach previously published by the authors with capabilities to address ternary diffusion systems and counter flow configurations. The model's core principle is modelling species transport by obtaining a 2D analytic solution for species concentration distribution in the plane perpendicular to the cannel gas-flow and coupling consecutive 2D solutions by means of a 1D numerical pipe-flow model. Electrochemical and other nonlinear phenomena are coupled to the species transport by a routine that uses derivative approximation with prediction-iteration. The latter is also the core of the counter-flow computation algorithm. A HAN model of a laboratory test fuel cell is presented and evaluated against a professional 3D CFD simulation tool showing very good agreement between results of the presented model and those of the CFD simulation. Furthermore, high accuracy results are achieved at moderate computational times, which is owed to the semi-analytic nature and to the efficient computational coupling of electrochemical kinetics and species transport. PMID- 25125113 TI - Rigid- and polarizable-ion potentials for modeling Ru-polyoxometalate catalysts for water oxidation. AB - This work assesses the predictive power and capabilities of classical interatomic potentials for describing the atomistic structure of a fully inorganic water oxidation catalyst in the gas phase and in solution. We address a Ru polyoxometalate molecule (Ru-POM) that is presently one of the most promising catalysts for water oxidation due to its efficiency and stability under reaction conditions. The Ru-POM molecule is modeled with two interatomic potentials, the rigid ion model and the shell model potentials, which are used to perform molecular dynamics simulations. The predictions of these two approaches are discussed and compared to the available ab-initio data. These results allow us to establish the suitable level of theory to model complex heterogeneous interfaces between the Ru-POM and electrodes in solution. PMID- 25125114 TI - Corrosion evaluation of zirconium doped oxide coatings on aluminum formed by plasma electrolytic oxidation. AB - The plasma electrolytic oxidation (PEO) of aluminum in sodium tungstate (Na(2)WO(4) . (2)H(2)O) and Na(2)WO(4) . (2)H(2)O doped with Zr was analyzed in order to obtain oxide coatings with improved corrosion resistance. The influence of current density in PEO process and anodization time was investigated, as well as the influence of Zr, with the aim to find out how they affect the chemical content, morphology, surface roughness, and corrosion stability of oxide coatings. It was shown that the presence of Zr increases the corrosion stability of oxide coatings for all investigated PEO times. Evolution of EIS spectra during the exposure to 3% NaCl, as a strong corrosive agent, indicated the highest corrosion stability for PEO coating formed on aluminum at 70 mA/cm(2) for 2 min in a zirconium containing electrolyte. PMID- 25125115 TI - Structure and dielectric properties of electrochemically grown ZrO2 films. AB - The dielectric properties of electrochemically grown zirconium oxide films by anodisation of zirconium in 1.0 mol dm-3 phosphoric acid solution were investigated in a 3 to 30 V potential range with a view to inducing surface modifications for eventual use in biomedical and electronic applications. The oxide films grown at different potentials were characterised by Atomic Force Microscopy, X-ray photoelectron and Raman spectroscopies; the latter demonstrated the incorporation of phosphate ions into the passive films. Flat band potentials calculated from the Mott-Shottky analysis of the oxides semiconducting properties confirm the bilayer structure of the films. The oxide dielectric permittivity was evaluated from impedance spectroscopy measurements and the film oxide model proposed gave values independent of the oxide growth potential. PMID- 25125116 TI - Optimizing the preparation procedure of self-assembled monolayer of stearic acid for protection of cupronickel alloy. AB - The aim of this work is to examine the possibility of CuNi protection in chloride media by self-assembled monolayers (SAMs) of stearic acid (SA). In order to obtain a compact, well ordered monolayer, that will provide long term protection, different SAM preparation procedures are studied. The influence of CuNi pretreatment, SA solution temperature and temperature of the drying period followed after the SA treatment on the protective properties of stearic acid self assembled layer are examined by electrochemical methods and surface analysis techniques. The obtained results show that for complete self-assembled film formation it is necessary to have a drying period after exposing the sample to the stearic acid solution. Heating of the SA solution and drying period at higher temperatures result in layers with better stability in chloride media. The most compact surface layer, that provides long lasting and efficient protection to the underlying alloy, is obtained when prior to SA solution exposure an oxide layer on CuNi surface was formed at elevated temperatures. PMID- 25125117 TI - Molecular modeling of organic corrosion inhibitors: why bare metal cations are not appropriate models of oxidized metal surfaces and solvated metal cations. AB - The applicability of various models of oxidized metal surfaces - bare metal cations, clusters of various size, and extended (periodic) slabs - that are used in the field of quantum-chemical modeling of corrosion inhibitors is examined and discussed. As representative model systems imidazole inhibitor, MgO surface, and solvated Mg(2+) ion are considered by means of density-functional-theory calculations. Although the results of cluster models are prone to cluster size and shape effects, the clusters of moderate size seem useful at least for qualitative purposes. In contrast, the bare metal cations are useless not only as models of oxidized surfaces but also as models of solvated cations, because they bind molecules several times stronger than the more appropriate models. In particular, bare Mg(2+) binds imidazole by 5.9 eV, while the slab model of MgO(001) by only 0.35 eV. Such binding is even stronger for 3+ cations, e.g., bare Al(3+) binds imidazole by 17.9 eV. The reasons for these fantastically strong binding energies are discussed and it is shown that the strong bonding is predominantly due to electron charge transfer from molecule to metal cation, which stems from differences between molecular and metal ionization potentials. PMID- 25125118 TI - Correlation between electronic and corrosion properties of the passive oxide film on nitinol. AB - The oxide film (TiO(2)) was formed on Nitinol potentiostatically in an acetic acid solution. Deep understanding of electronic properties of this film is needed to predict long-term corrosion properties of Nitinol implant material in simulated body fluid conditions. The capacitance measurements were performed under depletion conditions to study electronic (semiconducting) properties. The space charge, formed at the solid|liquid interface, creates the barrier for the corrosion processes in aggressive (bio)environment. According to the results of electrochemical impedance spectroscopy (EIS) and Mott-Schottky analysis (MS), the passive film on Nitinol behaves as amorphous highly-doped n-type semiconductor. The values of electronic structure parameters (the flat-band potential, E(fb) and the carrier (donor) density, N(D)) were corrected for frequency dispersion. PMID- 25125119 TI - Preparation and characterization of poly(5-aminoindole) by using electrochemical quartz crystal nanobalance technique. AB - The electrochemical quartz crystal nanobalance (EQCN) was employed to study the electropolymerization of 5-aminoindole on platinum electrodes in acidic media. Potentiostatic or potential cycling electrooxidation of 5-aminoindole below 0.62 V vs. SCE leads to the formation of uniform, yellow, electrochemically active polymeric films. A scheme of the redox transformations of poly(5-aminoindole) which involves protonation-deprotonation steps accompanying the electron transfer is suggested. At higher positive potentials, further oxidation takes place resulting in different blue-purple, indigo-type materials which remain attached to the metal surface but show decreased or no redox activity. PMID- 25125120 TI - Impedance of electrochemically modified graphite. AB - Electrochemical impedance spectroscopy, EIS, has been applied for characterization of electrochemically modified graphite electrodes in the sulphuric acid solution. Graphite modifications were performed by potential cyclization between potentials of graphite oxide formation/reduction, different number of cycles, and prolonged reduction steps after cyclization. Impedance spectra measured at two potential points within double-layer region of graphite have been successfully modeled using the concept of porous electrodes involving two different electrolyte diffusion paths, indicating existence of two classes of pores. The evaluated impedance parameter values show continuous changes with stages of graphite modification, indicating continuous structural changes of pores by number of potential cycles applied. Differences of impedance parameter values at two potential values indicate the potential induced changes of solution properties within the pores of modified graphite. PMID- 25125121 TI - Incorporation of cobalt-ferrite nanoparticles into a conducting polymer in aqueous micellar medium: strategy to get photocatalytic composites. AB - In this study an easy strategy for conducting polymer based nanocomposite formation is presented through the deposition of cobalt-ferrite (CoFe(2)O(4)) containing poly(3,4-ethylenedioxythiophene) (PEDOT) thin layers. The electrochemical polymerization has been performed galvanostatically in an aqueous micellar medium in the presence of the nanoparticles and the surface active Triton X-100. The nanoparticles have been characterized by Transmission electron microscopy (TEM), the thin layers has been studied by applying Scanning electron microscopy (SEM), and X-ray diffraction (XRD), and the basic electrochemical properties have been also determined. Moreover, electrocatalytic activity of the composite was demonstrated in the electrooxidation reaction of dopamine (DA). The enhanced sensitivity - related to the cobalt-ferrite content - and the experienced photocatalyitic activity are promising for future application. PMID- 25125122 TI - Electronic absorption spectra and nonlinear optical properties of ruthenium acetylide complexes: a DFT study toward the designing of new high NLO response compounds. AB - In this study we have used density functional theory (DFT) to calculate nonlinear optical properties and simulate the UV-VIS absorption spectra of ruthenium acetylide complexes.Among the studied systems, system 4 has shown highest non linear optical properties (a = 72.92 * 10(-24)esu and b = 76.32 * 10(-30)esu).New compounds have been theoretically designed by the extension of conjugation length and substitution of electron withdrawing atom/groups as acceptor on system 4. All designed compounds show intense band due to metal-to-ligand charge transfer (MLCT).Second-order polarizabilityof new design compounds was remarkablyhigh as compared to system 4 (123.35 * 10(-30)to 360.23 * 10(-30)esu). Effect of acceptors was more prominent than pi-spacers. Results of theoretical investigation indicate that all systems should be excellent non-linear optical materials. PMID- 25125123 TI - Effects of different gas phases and gas bubbles on the nucleation kinetics. AB - In this study, the effects of different gas phases and gas bubbles on the Induction time were investigated. In the first step, the effects of different kinds of gases (N(2), Ar, dry air-N(2) and dry air-Ar) which are fed into solution-gas interphase and into the solution were determined. After determining the most effective gas upon the Induction time, the next step was to use this gas in the presence of the seed crystals, to specify variation in the Induction time. The experimental results show that gassing and the presence of seed crystal tend to shorten the Induction time as compared to the normal crystallization condition. PMID- 25125125 TI - Photodegradation of 4-methylphenol on palladium phthalocyaninesulfonate functionalized mesopolymer under visible light irradiation. AB - A versatile photocatalyst has been prepared by grafting palladium phthalocyaninesulfonate (PdPcS) onto the FDU-14 mesopolymer with 3-D cubic mesostructure (FDU-14-PdPcS) via multi-step chemical modification processes. The FDU-14-PdPcS was characterized by the X-ray diffraction (XRD), diffuse reflectance UV-vis spectroscopy and inductively coupled plasma (ICP) techniques. In the photodegradation studies of 4-methylphenol, the FDU-14-PdPcS catalyst exhibited excellent visible light photocatalytic activity and reusability in the present of H(2)O(2). The photodegradation intermediate of 4-methylphenol was investigated by gas chromatoghraphy-mass spectrometry (GC-MS) technique. Quenching experiments with isopropanol, sodium azide and benzoquinone suggested that (1)O(2) and O(2)(*-) were the prominent active species during the photodegradation process. A possible mechanism involved in the photodegradation of 4-methylphenol has also been discussed. PMID- 25125124 TI - Adsorptive stripping voltammetry of antibiotics rifamycin SV and rifampicin at renewable pencil electrodes. AB - Adsorptive stripping voltammetry of antibiotics of rifamycin SV (RSV) and rifampicin (RIF) was investigated by cyclic voltammetry and differential pulse voltammetry using a renewable pencil graphite electrode (PGE). The nature of the oxidation process of RSV and RIF taking place at the PGE was characterized. The results show that the determination of highly sensitive oxidation peak current is the basis of a simple, accurate and rapid method for quantification of RSV and RIF in bulk forms, pharmaceutical formulations and biological fluids by differential pulse adsorptive stripping voltammetry (DPASV). Factors influencing the trace measurement of RSV and RIF at PGE are assessed. The limits of detection for the determination of RSV and RIF in bulk forms are 6.0 * 10(-8) mol/L and 1.3 * 10(-8) mol/L, respectively. Moreover, the proposed procedure was successfully applied to assay both RSV and RIF in pharmaceutical formulations and in biological fluids. The capability of the proposed procedure for simultaneous assay of antibiotics RSV-isoniazid and RIF-isoniazid was achieved. The statistical analysis and calibration curve data for trace determination of RSV and RIF are reported. PMID- 25125126 TI - Polymer nanoparticles containing 2,4,6-triiodophenol: a potential contrast medium for medical imaging. AB - Contrast agents have been utilized for x-ray imaging to visualize blood vessels. Triiodobenzene derivatives are known contrast agents yet have not been formulated in a nanoparticle form for the purpose of enhancing the contrast of cancer tissues. In this study, experiments to encapsulate 2,4,6-triiodophenol in a polymer matrix were designed. Spherical NPs made of PLA, PLGA, PLA-TPGS, PLGA TPGS and TPGS-FOL, were synthesized and characterized. Using the oil-in-water single-emulsion technique, the effect of several experimental parameters such as sonication power, ratio of 2,4,6-triiodophenol/polymer, type and concentration of emulsifier, and polymer type has been studied. A good morphology of polymer NPs with entrapped 2,4,6-triiodophenol was successfully obtained however the encapsulated iodine was in the range of 5 to 26%. PMID- 25125127 TI - Synthesis of 3',4'-dihydro-2H,2'H,5H-spiro [imidazolidine-4,1'-naphthalene]-2,5 dione and its derivatives. AB - The synthesis of two novel compounds, 1-amino-3',4'-dihydro-2H,2'H,5H spiro[imidazolidine-4,1'-naphthalene]-2,5-dione and 1,3-bis(hydroxymethyl)-3',4' dihydro-2H,2'H,5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, was reported. The structures of the compounds were verified by (1)H, (13)C NMR and IR spectroscopy and quantum-chemical calculations at DFT level. PMID- 25125128 TI - Colchicine levels in chronic kidney diseases and kidney transplant recipients using tacrolimus. AB - BACKGROUND: Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. In this study, we aimed to evaluate plasma colchicine levels in different stages of kidney disease as well as in kidney transplant (KTx) recipients using tacrolimus. METHOD: This study included six familial Mediterranean fever (FMF) patients with normal glomerular filtration rate (GFR) as controls, three patients with low GFR, six FMF patients on hemodialysis (HD), and six FMF patients who were KTx recipients using tacrolimus. After a three-d washout period, plasma colchicine levels were measured at 0 (pre-dose), one, two, four, eight, and 24 h post-dose of 1 mg oral colchicine. Area under the curve 0-24 h (AUC0-24 ) and maximum concentration (Cmax ) were evaluated and compared between the groups. RESULTS: Colchicine AUC0-24 was six-fold higher in HD (p < 0.001) and three-fold higher in KTx recipients (p < 0.001) when compared to the control. The low GFR group had mildly higher AUC0-24 than the control group. Cmax levels were also higher in HD (p = 0.011) and KTx recipient (p = 0.06) groups and mildly elevated in low GFR patients in comparison with controls. CONCLUSION: Colchicine AUC0-24 and Cmax were significantly increased in HD patients and KTx recipients using tacrolimus. Therefore, dose adjustments are needed to avoid toxicity in both circumstances. PMID- 25125129 TI - Flow cytometry-based assay to study HIV-1 gp120 specific antibody-dependent cellular cytotoxicity responses. AB - Increased attention on the role of Fc-mediated effector functions against HIV-1 has led to renewed interest into the role that antibody-dependent cellular cytotoxicity (ADCC) could play in controlling viral transmission and/or the rate of disease progression. While (51)Chromium release assays have traditionally been used to study ADCC responses against HIV-1, a number of alternative flow cytometry-based assays were recently developed. In this study, an alternative flow-cytometry-based assay was established to allow non-radioactive measurement of ADCC-mediated elimination of HIV-1 gp120 envelope glycoprotein (Env)-coated target cells. This assay relies on staining target and effector cells with different dyes, which allows precise gating and permits the calculation of the number of surviving target cells by normalization to flow-cytometry particles. By using small concentrations of recombinant gp120 Env, suitable targets cells that recapitulate the ADCC response mediated against HIV-1-infected cells were generated. Finally, this method was applied successfully to screen human sera for ADCC activity directed against HIV-1 gp120 Env. PMID- 25125131 TI - Guest editorial: sleepers awake! Older people are our future (or beige is the new black). PMID- 25125130 TI - Optimal transfection methods and comparison of PK-15 and Dulac cells for rescue of chimeric porcine circovirus type 1-2. AB - A chimeric porcine circovirus type 1-2 (PCV1-2) infectious DNA clone has low transfection efficiency and exhibits low levels of proliferation. Electroporation and lipofection parameters were optimized for PK-15 and Dulac cells with the purpose of increasing the efficiency for rescuing infectious PCV1-2. Titers of PCV1-2 in Dulac cells were 100-fold higher than those in PK-15 cells following transfection. The electroporation efficiency into Dulac cells was high when three 400 MUs pulses at 250 V with 6 MUg of plasmid DNA was used, lipofection efficiency was high when the ratio of DNA to transfection reagent was 1:3. The proportion of infected cells was 55.6% compared with 44.2%, for the electroporation and lipofection techniques respectively. Virus titers were higher in Dulac cells, from 10(4.44) to 10(5.32)TCID50/mL compared with 10(1.90) 10(3.38)TCID(50)/mL for PK-15 cells. Dulac cells were more permissive to PCV1-2 than PK-15 cells regardless of the transfection technique. PMID- 25125132 TI - Laser all-ceramic crown removal-a laboratory proof-of-principle study-phase 1 material characteristics. AB - BACKGROUND AND OBJECTIVES: The removal of all-ceramic crowns is a time consuming and destructive procedure in the dental office. The removal of all-ceramic crowns using Er:YAG lasers has not been previously described in the scientific literature. The objective of this laboratory proof-of-principle study was to evaluate whether with regards to absorption and transmission characteristics of bonding cements and ceramics all-ceramic crowns can be removed from natural teeth using an Erbium laser. STUDY DESIGN/MATERIALS AND METHODS: The Fourier Transform Infrared Spectroscopy (FTIR) was used on flat ceramic samples (IPS Empress Esthetic (EE), E.max CAD, and E.max ZirCAD) to assess which infrared laser wavelengths transmit through the ceramics. Additionally, FTIR spectra for four bonding cements (Variolink Veneer, Variolink II, Multilink Automix, and SpeedCEM) were obtained. The Er:YAG laser energy transmission (wavelength 2,940 nm, 10 Hz repetition rate, pulse duration 100 us at 126 mJ/pulse to 300 us at 508 mJ/pulse) through different ceramic thicknesses was measured. Ablation thresholds for bonding cements were determined. Cement samples were directly irradiated or laser light was transmitted through ceramic samples. RESULTS: While the ceramics did not show any characteristic water absorption bands in the FTIR, all bonding cements showed a broad H2 O/OH absorption band. Some cements exhibited a distinct absorption peak at the Er:YAG laser emission wavelength. Depending on the ceramic thickness, EE and E.max CAD ceramics transmitted between 21 and 60% of the incident Er:YAG energy, with E.max CAD transmitting more energy than EE at comparable thicknesses. In contrast, E.max ZirCAD transmitted only 5-10% of the incident energy. Initial signs of cement deterioration occurred at 1.3-2.6 J/cm(2) . Multilink Automix, SpeedCEM, and Variolink II started ablation at 4.4 4.7 J/cm(2) . Variolink Veneer needed 44% less energy for ablation. CONCLUSION: Er:YAG laser energy can be transmitted through all-ceramic materials and those transmitted energies are sufficient for ablation of bonding cements. PMID- 25125133 TI - The effect of IL-17 on the production of proinflammatory cytokines and matrix metalloproteinase-1 by human periodontal ligament fibroblasts. AB - OBJECTIVES: To investigate the effects of IL-17 on IL-6, IL-1beta, and matrix metalloproteinase (MMP-1) production, and to compare the MMP-1 production between the individual and combined effects of IL-1beta and IL-6 in human periodontal ligament fibroblasts (HPDLF). MATERIALS AND METHODS: Human periodontal ligament fibroblasts were cultured with IL-17 for 0.5, 1, 4, 24, 48, and 72 h, and were cultured with IL-1beta, IL-6/sIL-6R, or a combination of IL-1beta and IL-6/sIL-6R for 24 h. To measure the mRNA levels of IL-6, IL-1beta, and MMP-1, total RNA was extracted from the cultured HPDLF, and a real-time PCR analysis was performed. The protein levels of IL-6, IL-1beta, and MMP-1 in supernatants were measured using enzyme-linked immunosorbent assays (ELISAs). RESULTS: IL-17 significantly increased the expression of IL-6 and MMP-1 mRNA and protein, while IL-17 transiently increased the expression of IL-1beta mRNA. The combination of IL 1beta and IL-6/sIL-6R induced significantly higher levels of MMP-1 protein than IL-1beta alone. CONCLUSIONS: IL-17 upregulated the production of IL-6 and MMP-1 sequentially in HPDLF. IL-6/sIL-6R may enhance the effects of IL-1beta on MMP-1 production. The present results suggest that IL-17 induces MMP-1 production not only directly, but also indirectly by promoting IL-6 production, thus resulting in the degradation of collagens in the PDL. PMID- 25125134 TI - An extrafacial amelanotic lentigo maligna of the leg: a case report. PMID- 25125135 TI - Prevalence of sinonasal disease in children with Juvenile idiopathic arthritis. AB - OBJECTIVES/HYPOTHESIS: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is caused by a multitude of well studied disorders. However, the association between JIA and/or its treatment and sinonasal inflammatory disease (SNID) has never been studied. We therefore investigated this relationship to gain more insight into burdening pathologies connected to JIA. STUDY DESIGN: Retrospective evaluation. METHODS: A retrospective evaluation according to the Lund-Mackay score of cone-beam computed tomography scans (CBCT) performed in 70 children affected by JIA and compared to CBCT scans of 124 healthy controls was conducted. The prevalence of sinonasal opacification and adenoid hypertrophy in patients affected with JIA was compared with findings obtained in unaffected children. RESULTS: JIA was significantly associated with SNID (P = .030). Of patients with JIA, 18.6% had SNID, whereas in children without JIA, only 8.1% had SNID. The odds ratio values were 5.38 (95% confidence interval [CI]: 1.90-15.26) for treated and 0.92 (95% CI: 0.18-4.83) for untreated JIA. No clear difference was found depending on the duration of JIA. No association was found between adenoid hypertrophy and SNID (P = .816). CONCLUSIONS: Our data suggest that JIA patients, especially when undergoing immunosuppressive therapy, should be subjected to an ear, nose, and throat evaluation. A prospective study including clinical evaluation would be of the utmost importance to provide evidence on which to base comprehensive healthcare for these patients. LEVEL OF EVIDENCE: 3b. PMID- 25125136 TI - Identification and characterization of a pesticide degrading flavobacterium species EMBS0145 by 16S rRNA gene sequencing. AB - Organophosphates (OPs) like chlorpyrifos, diazinon, or malathion have become most common and indisputably most toxic pest-control agents that adversely affects the human nervous system even at low levels of exposure. Because of their relatively low cost and ability to be applied on a wide range of target insects and crop, organophosphorus pesticides account for a large share of all insecticides used in India, this in turn raises severe health concerns. In this view, the present investigation was aimed to identify novel species of Flavobacterium bacteria which is bestowed with the capacity to degrade pesticides like chlorpyrifos, diazinon or malathion. The bacterium was isolated from agricultural soil collected from Guntur District, Andhra Pradesh, India. The samples were serially diluted and the aliquots were incubated for a suitable time following which the suspected colony was subjected to 16S rRNA gene sequencing. The sequence thus obtained was aligned pairwise against Flavobacterium species, which resulted in identification of novel species of Flavobacterium later which was named as EMBS0145 and sequence was deposited in GenBank with accession number JN794045. PMID- 25125137 TI - Association between TNF-alpha-308 G/A gene polymorphism and gastric cancer risk: a systematic review and meta-analysis. AB - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) has been found to be associated with gastric carcinogenesis, but individually published results have been inconclusive. The aim of this study was to explore the relationship between the TNF-alpha-308 G/A polymorphism and gastric cancer risk. METHODS: MEDLINE, EMBASE and the COCHRANE library databases were searched for relevant articles to identify all available data. The odds ratios (ORs) with 95% confidence intervals (95% CIs) from each study were used to assess the association between the TNF alpha-308 G/A polymorphism and gastric cancer risk. RESULTS: This meta-analysis included 30 studies (32 datasets) involving 7009 gastric cancer cases and 12,119 control subjects. Overall, a significant association was found between the TNF alpha-308 G/A polymorphism and gastric cancer in AA+GA vs. GG (dominant contrast model) (OR=1.20, 95% CI=1.07-1.34, p=0.001). With stratification based on ethnicity, the TNF-alpha-308 G/A polymorphism was correlated with gastric cancer risk in Caucasians, using the dominant contrast model (OR=0.74, 95% CI=0.57-0.96, p=0.02), but not in East Asians and other ethnic groups. In the comprehensive subgroup analysis, a significant association was also found in recent articles (published after 2005), population-based high-quality studies, hospital-based high-quality studies, studies using the TaqMan method and non-cardia subgroups. However, the TNF-alpha-308 G/A polymorphism was not associated with specific histological types of gastric cancer risk. CONCLUSIONS: The TNF-alpha-308 G/A polymorphism may contribute to susceptibility to gastric cancer in Caucasians, especially for non-cardia gastric cancer, as most strongly demonstrated in high quality studies and in studies using the TaqMan genotyping method. Furthermore, we recommend the TaqMan method as the preferred genotyping method in DNA polymorphism studies. PMID- 25125139 TI - Influence of gonadotrophin-induced first oestrus on gilt fertility. AB - The aim of this study was to determine the association between the oestrous response of pre-pubertal gilts to gonadotrophin injection or boar exposure and their subsequent farrowing rate and litter size. At 154 days of age, randomly selected pre-pubertal gilts received an intramuscular injection of 400 IU equine chorionic gonadotrophin plus 200 IU human chorionic gonadotrophin (PG600((r)) ; Merck Animal Health; n = 181). From the remaining pool of animals not treated with hormones, the first gilts showing signs of oestrus were selected to act as controls (n = 201). Boar exposure began at 155 days of age for both groups, and gilts were bred at a weight of approximately 130 kg. Comparisons were made between PG600((r)) -treated gilts exhibiting oestrus or not within 7 days post injection (early and late responders, respectively) and control gilts exhibiting oestrus or not within 30 days after beginning of boar exposure (select and non select control gilts, respectively). By 162 days, oestrus was detected in 67.5% of PG600((r)) -treated gilts compared with 5.7% of control gilts (p < 0.0001). The proportion of animals observed in oestrus at least three times before breeding was greater for select control gilts compared with early and late responder PG600((r)) -treated gilts (p <= 0.001). There were no significant differences in farrowing rate and litter size between the four treatment groups. These data indicate that PG600((r)) is an effective tool to induce an earlier oestrus in gilts, that subsequent farrowing rate and born alive litter size compare favourably to that of select gilts and that gilts failing to respond promptly to hormonal stimulation do not exhibit compromised fertility. PMID- 25125140 TI - A structured blood conservation programme reduces transfusions and costs in cardiac surgery. AB - OBJECTIVES: Transfusions of blood products can be lifesaving, but they are also associated with considerable risks and adverse effects, including immune response and infections. In cardiac surgery, transfusions have also been associated with increased mortality. We prospectively studied the effects of a structured programme to reduce transfusions and transfusion-associated costs in cardiac surgery. METHODS: The programme included: (i) education of all staff about the risks and benefits of blood transfusions; (ii) revised guidelines for transfusions; and (iii) a transfusion log where indication for transfusion, status of the patient and prescribing physician were registered. Transfusion prevalence, complications and costs for blood products were registered for all acute and elective cardiac operations during a 12-month period before (n = 1128) and after (n = 1034) the programme was started. The two time periods were compared. In addition, the prevalence of transfusions was registered for 2 more years after the programme was initiated. RESULTS: The first year after the programme was initiated the proportion of patients transfused with red blood cell concentrate decreased by 21.8% (from 58.2 to 45.5%, P <0.001), plasma by 37.4% (from 30.8 to 19.3%, P <0.001) and platelets by 21.0% (from 20.5 to 16.2%, P = 0.010). Reoperations for bleeding (5.8 vs 5.0%), early complication rate and 30 day mortality (2.5 vs 2.6%) were not significantly different before and after the start date. Based on the 2009 institutional prices for red blood cell concentrate (102 ?/unit), plasma (35 ?/unit) and platelets (290 ?/unit), the savings on blood products were ?161,623 during the first 12 months after the programme was launched. The proportion of patients transfused with any blood product was 60.9% before the programme was started and 48.3, 54.0 and 50.7% 1-3 years after its start (all P <0.001), respectively. CONCLUSIONS: A structured blood conservation programme reduces transfusions and costs for blood products in cardiac surgery, without any signs of compromised medical safety. The effects of introducing such a programme are maintained over at least 3 years. PMID- 25125138 TI - Maternal and perinatal outcomes after bariatric surgery: a Spanish multicenter study. AB - BACKGROUND: Bariatric surgery (BS) has become more frequent among women of child bearing age. Data regarding the underlying maternal and perinatal risks are scarce. The objective of this nationwide study is to evaluate maternal and perinatal outcomes after BS. METHODS: We performed a retrospective observational study of 168 pregnancies in 112 women who underwent BS in 10 tertiary hospitals in Spain over a 15-year period. Maternal and perinatal outcomes, including gestational diabetes mellitus (GDM), pregnancy-associated hypertensive disorders (PAHD), pre-term birth cesarean deliveries, small and large for gestational age births (SGA, LGA), still births, and neonatal deaths, were evaluated. Results were further compared according to the type of BS performed: restrictive techniques (vertical-banded gastroplasty, sleeve gastrectomy, and gastric banding), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion (BPD). RESULTS: GDM occurred in five (3 %) pregnancies and there were no cases of PAHD. Women whose pregnancies occurred before 1 year after BS had a higher pre gestational body mass index (BMI) than those who got pregnant 1 year after BS (34.6 +/- 7.7 vs 30.4 +/- 5.3 kg/m(2), p = 0.007). In pregnancies occurring during the first year after BS, a higher rate of stillbirths was observed compared to pregnancies occurring after this period of time (35.5 vs 16.8 %, p = 0.03). Women who underwent BPD delivered a higher rate of SGA babies than women with RYGB or restrictive procedures (34.8, 12.7, and 8.3 %, respectively). CONCLUSIONS: Pregnancy should be scheduled at least 1 year after BS. Malabsorptive procedures are associated to a higher rate of SGA births. PMID- 25125142 TI - Rhodium(III)-catalyzed C-C and C-O coupling of quinoline N-oxides with alkynes: combination of C-H activation with O-atom transfer. AB - [Cp*Rh(III)]-catalyzed C-H activation of arenes assisted by an oxidizing N-O or N N directing group has allowed the construction of a number of hetercycles. In contrast, a polar N-O bond is well-known to undergo O-atom transfer (OAT) to alkynes. Despite the liability of N-O bonds in both C-H activation and OAT, these two important areas evolved separately. In this report, [Cp*Rh(III)] catalysts integrate both areas in an efficient redox-neutral coupling of quinoline N-oxides with alkynes to afford alpha-(8-quinolyl)acetophenones. In this process the N-O bond acts as both a directing group for C-H activation and as an O-atom donor. PMID- 25125141 TI - Oesophageal pyomyositis in an intravenous drug user. AB - An inflammatory or infectious disease of the oesophagus occurring in tissue layers beneath but sparing the mucosa may pose a diagnostic challenge. Bacterial pyomyositis has been previously reported occurring mostly in the skeletal muscle. Pyomyositis involving the gastrointestinal tract is extremely rare, and may easily be misdiagnosed due to its nonspecific clinical features. We report a case of an intravenous drug user who presented with oesophageal pyomyositis. Early computed tomography facilitated accurate diagnosis. Adequate drainage followed by antibiotic treatment was effective and the oesophagus was preserved. To the best of our knowledge, this is the first report of a case of oesophageal myositis in an intravenous drug user. PMID- 25125143 TI - Highly efficient and excitation tunable two-photon luminescence platform for targeted multi-color MDRB imaging using graphene oxide. AB - Multiple drug-resistance bacteria (MDRB) infection is one of the top three threats to human health according to the World Health Organization (WHO). Due to the large penetration depth and reduced photodamage, two-photon imaging is an highly promising technique for clinical MDRB diagnostics. Since most commercially available water-soluble organic dyes have low two-photon absorption cross-section and rapid photobleaching tendency, their applications in two-photon imaging is highly limited. Driven by the need, in this article we report extremely high two photon absorption from aptamer conjugated graphene oxide (sigma2PA = 50800 GM) which can be used for highly efficient two-photon fluorescent probe for MDRB imaging. Reported experimental data show that two-photon photoluminescence imaging color, as well as luminescence peak position can be tuned from deep blue to red, just by varying the excitation wavelength without changing its chemical composition and size. We have demonstrated that graphene oxide (GO) based two photon fluorescence probe is capable of imaging of multiple antibiotics resistance MRSA in the first and second biological transparency windows using 760 1120 nm wavelength range. PMID- 25125144 TI - Chromosomal rearrangements directly cause underdominant F1 pollen sterility in Mimulus lewisii-Mimulus cardinalis hybrids. AB - Chromosomal rearrangements can contribute to the evolution of postzygotic reproductive isolation directly, by disrupting meiosis in F1 hybrids, or indirectly, by suppressing recombination among genic incompatibilities. Because direct effects of rearrangements on fertility imply fitness costs during their spread, understanding the mechanism of F1 hybrid sterility is integral to reconstructing the role(s) of rearrangements in speciation. In hybrids between monkeyflowers Mimulus cardinalis and Mimulus lewisii, rearrangements contain all quantitative trait loci (QTLs) for both premating barriers and pollen sterility, suggesting that they may have facilitated speciation in this model system. We used artificial chromosome doubling and comparative mapping to test whether heterozygous rearrangements directly cause underdominant male sterility in M. lewisii-M. cardinalis hybrids. Consistent with a direct chromosomal basis for hybrid sterility, synthetic tetraploid F1 s showed highly restored fertility (83.4% pollen fertility) relative to diploids F1 s (36.0%). Additional mapping with Mimulus parishii-M. cardinalis and M. parishii-M. lewisii hybrids demonstrated that underdominant male sterility is caused by one M. lewisii specific and one M. cardinalis specific reciprocal translocation, but that inversions had no direct effects on fertility. We discuss the importance of translocations as causes of reproductive isolation, and consider models for how underdominant rearrangements spread and fix despite intrinsic fitness costs. PMID- 25125145 TI - Transcription activator-like effector nuclease (TALEN)-mediated female-specific sterility in the silkworm, Bombyx mori. AB - Engineering sex-specific sterility is critical for developing transgene-based sterile insect technology. Targeted genome engineering achieved by customized zinc-finger nuclease, transcription activator-like effector nuclease (TALEN) or clustered, regularly interspaced, short palindromic repeats/Cas9 systems has been exploited extensively in a variety of model organisms; however, screening mutated individuals without a detectable phenotype is still challenging. In addition, genetically recessive mutations only detectable in homozygotes make the experiments time-consuming. In the present study, we model a novel genetic system in the silkworm, Bombyx mori, that results in female-specific sterility by combining transgenesis with TALEN technologies. This system induces sex-specific sterility at a high efficiency by targeting the female-specific exon of the B. mori doublesex (Bmdsx) gene, which has sex-specific splicing isoforms regulating somatic sexual development. Transgenic animals co-expressing TALEN left and right arms targeting the female-specific Bmdsx exon resulted in somatic mutations and female mutants lost fecundity because of lack of egg storage and abnormal external genitalia. The wild-type sexual dimorphism of abdominal segment was not evident in mutant females. In contrast, there were no deleterious effects in mutant male moths. The current somatic TALEN technologies provide a promising approach for future insect functional genetics, thus providing the basis for the development of attractive genetic alternatives for insect population management. PMID- 25125147 TI - Influence of minimally invasive total hip replacement on hip reaction forces and their orientations. AB - Minimally invasive surgery (MIS) is becoming increasingly popular. Supporters claim that the main advantages of MIS total hip replacement (THR) are less pain and a faster rehabilitation and recovery. Critics claim that safety and efficacy of MIS are yet to be determined. We focused on a biomechanical comparison between surgical standard and MIS approaches for THR during the early recovery of patients. A validated, parameterized musculoskeletal model was set to perform a squat of a 50th percentile healthy European male. A bilateral motion was chosen to investigate effects on the contralateral side. Surgical approaches were simulated by excluding the incised muscles from the computations. Resulting hip reaction forces and their symmetry and orientation were analyzed. MIS THR seemed less influential on the symmetry index of hip reaction forces between the operated and nonoperated leg when compared to the standard lateral approach. Hip reaction forces at peak loads of the standard transgluteal approach were 24% higher on the contralateral side when compared to MIS approaches. Our results suggest that MIS THR contributes to a greater symmetry of hip reaction forces in absolute value as well as force-orientation following THR. PMID- 25125148 TI - Enlightened oncologists can provide quality cancer care at reduced costs. PMID- 25125146 TI - Relevance of the myeloid differentiation factor 88 (MyD88) on RANKL, OPG, and nod expressions induced by TLR and IL-1R signaling in bone marrow stromal cells. AB - The myeloid differentiation factor 88 (MyD88) plays a pivotal role in Toll-like receptor (TLR)- and interleukin-1 receptor (IL-1R)-induced osteoclastogenesis. We examined the role of MyD88 on p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappaB) activation and nucleotide-binding oligomerization domain (Nod) induction by lipopolysaccharide (LPS) and IL-1 beta, and their effect on receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) production in bone marrow stromal cell (BMSC). RANKL, Nod1, Nod2, NF-kappaB, and p38 protein levels were determined by Western blot. Nod2 was stimulated with muramyl dipeptide (MDP) prior to TLR4 stimulation with LPS. MyD88 deficiency markedly inhibited RANKL expression after LPS stimulation and increased OPG messenger RNA (mRNA) production. Also, MyD88 was necessary for NF-kappaB and p38 MAPK activation. MDP alone did not induce RANKL and OPG expressions; however, when combined with LPS, their expressions were significantly increased (p < 0.05). Our results support that MyD88 signaling has a pivotal role in osteoclastogenesis thought NF-kappaB and p38 activation. Nod2 and especially Nod1 levels were influenced by MyD88. PMID- 25125149 TI - The variability of ecstasy tablets composition in Brazil. AB - The content of ecstasy tablets has been changing over the years, and nowadays 3,4 methylenedioxymethamphetamine (MDMA) is not always present in the tablets. The aim of this study was to investigate the chemical composition in the seized tablets labeled as ecstasy. We analyzed samples from 150 different seizures made by Sao Paulo's State Police by gas chromatography-mass spectrometry. MDMA was present in 44.7% of the analyzed samples, and another twenty different active substances were identified in these tablets, such as caffeine, 2C-B, piperazines, amphetamines, phencyclidine, and others. Methamphetamine was present in 22% of these samples. The results demonstrate a huge shift in the pattern of trafficking of synthetic drugs, where MDMA has been replaced in tablets mostly by illicit psychoactive substances, in a clear attempt to bypass the law. The great variability in the tablets composition may lead to an increased risk of drug poisoning. PMID- 25125151 TI - Next-generation therapeutics. PMID- 25125152 TI - Nepal may have enough doctors but they're in the wrong place. PMID- 25125150 TI - NDST1 missense mutations in autosomal recessive intellectual disability. AB - NDST1 was recently proposed as a candidate gene for autosomal recessive intellectual disability in two families. It encodes a bifunctional GlcNAc N deacetylase/N-sulfotransferase with important functions in heparan sulfate biosynthesis. In mice, Ndst1 is crucial for embryonic development and homozygous null mutations are perinatally lethal. We now report on two additional unrelated families with homozygous missense NDST1 mutations. All mutations described to date predict the substitution of conserved amino acids in the sulfotransferase domain, and mutation modeling predicts drastic alterations in the local protein conformation. Comparing the four families, we noticed significant overlap in the clinical features, including both demonstrated and apparent intellectual disability, muscular hypotonia, epilepsy, and postnatal growth deficiency. Furthermore, in Drosophila, knockdown of sulfateless, the NDST ortholog, impairs long-term memory, highlighting its function in cognition. Our data confirm NDST1 mutations as a cause of autosomal recessive intellectual disability with a distinctive phenotype, and support an important function of NDST1 in human development. PMID- 25125154 TI - [The evolution of national health and the development of the nursing practice in Taiwan]. AB - Nursing is an applied science. While there is a wide range of nursing theories and nursing care models, resolving the health problems and meeting the health needs of clients is the common objective of all in the nursing profession. The nursing profession may be subdivided into hospital clinical nursing and community health nursing (CHN). CHN is further subdivided into public health nursing, school health nursing, and industrial health nursing. The past 60 years has been a period of significant growth and improvement in Taiwan that has enhanced the nation's socioeconomic condition, general living standards, and general public health. The nursing profession has seen profound progress as well, not only in terms of content but also in terms of nursing care models, which are increasingly framed around core public health needs and take into consideration different health perspectives. Nursing in Taiwan has gradually established its own professional function and autonomy. PMID- 25125155 TI - [The Taiwan Nurses Association and professional diplomacy]. AB - The Taiwan Nurses Association (TWNA) is publishing a special centenary issue to commemorate the 100th anniversary of the association in 2014. For this issue, TWNA invited the author to write a review article that addresses the involvement of the TWNA in professional diplomacy and international exchange over the past century. The author reviews the history of both TWNA and the International Council of Nurses and introduces the contributions of the association in the field of professional diplomacy and the positive contributions of many Taiwan nursing leaders to global healthcare and society. The purpose of the paper is to convey the traditions and experiences of TWNA forward to the next generation. PMID- 25125156 TI - ["Scholar officials": thoughts on the involvement of professional nurses in the political process]. AB - A growing number of nurses are concerned with / participate in public affairs, politics, and policymaking processes. In particular, nursing leaders are actively leveraging their collective power to create interdisciplinary alliances aimed at encouraging the media and government to confront key nursing issues and implement healthcare reform. This article highlights the political participation and policy making process to address the meaning and essence of politics, politics and nursing, training and strategies of public affairs and political participation, the shift from academia to health policy, and facilitation of important health policies. It is hoped that nurses may appropriately use their status and influence to actively participate in political campaigns and the policymaking process. By using their professional knowledge and skills, nurses may not only protect patient safety and public health but also facilitate nursing professional development and promote the professional image of nursing. PMID- 25125153 TI - Hypertonic sodium lactate improves fluid balance and hemodynamics in porcine endotoxic shock. AB - INTRODUCTION: Based on the potential interest in sodium lactate as an energy substrate and resuscitative fluid, we investigated the effects of hypertonic sodium lactate in a porcine endotoxic shock. METHODS: Fifteen anesthetized, mechanically ventilated pigs were challenged with intravenous infusion of E. coli endotoxin. Three groups of five animals were randomly assigned to receive 5 mL/kg/h of different fluids: a treatment group received hypertonic sodium lactate 11.2% (HSL group); an isotonic control group receiving 0.9% NaCl (NC group); a hypertonic control group with the same amount of osmoles and sodium than HSL group receiving hypertonic sodium bicarbonate 8.4% (HSB group). Hemodynamic and oxygenation variables, urine output and fluid balance were measured at baseline and at 30, 60, 120, 210 and 300 min. Skin microvascular blood flow at rest and during reactive hyperemia was obtained using a laser Doppler flowmetry technique. Results were given as median with interquartile ranges. RESULTS: Endotoxin infusion resulted in hypodynamic shock. At 300 min, hemodynamics and oxygenation were significantly enhanced in HSL group: mean arterial pressure (103 [81-120] mmHg vs. 49 [41-62] in NC group vs. 71 [60-78] in HSB group), cardiac index (1.6 [1.2-1.8] L/min/m2 vs. 0.9 [0.5-1.1] in NC group vs. 1.3 [0.9-1.6] in HSB group) and partial pressure of oxygen (366 [308-392] mmHg vs. 166 [130-206] in NC group vs. 277 [189-303] in HSB group). At the same time, microvascular reactivity was significantly better in HSL group with a lower venoarterial CO2 tension difference (5.5 [4-10] mmHg vs. 17 [14-25] in NC group vs. 14 [12-15] in HSB group). The cumulative fluid balance was lower in HSL group (-325 [-655; -150] mL) compared to NC (+560 [+230; +900] mL, p = 0.008) and HSB (+185 [-110; +645] mL, p = 0.03) groups. CONCLUSIONS: In our hypodynamic model of endotoxic shock, infusion of hypertonic sodium lactate improves hemodynamic and microvascular reactivity with a negative fluid balance and a better oxygenation. PMID- 25125157 TI - [Centennial retrospective on the evolution and development of the nursing practice environment in Taiwan]. AB - The practice environment for nurses has seen tremendous change over the past century due to the dedication and trailblazing work of nursing pioneers. This article describes how the nursing practice environment in Taiwan has evolved over this period. References used include nursing narratives, hospital accreditation standards, standard operating procedures, workplace safety standards, and worksite-related values and expectations. The efforts of the professional nursing community to realize a positive practice environment are further discussed. Over this century of change, the only thing that has remained unchanged is the commitment of nurses to "treat patients as one's own family". In the current as well as the previous periods of manpower shortages in nursing, the nursing community has managed to turn crisis into opportunity by using the situation to enhance pay and benefits. Nursing professionalism is widely respected and recognized throughout Taiwan society. The rapidly changing needs of the 21st century in aspects such as the advancement of high technology, the rapid growth of the elderly population, and the fast rate of social change seriously impact the development of the nursing profession. How to effectively apply high technology, simplify workflows, provide high quality and humanistic nursing care, build safe and quality workplaces, attract bright nursing students, and provide healthcare for the entire population will remain the responsibilities of nursing for generations to come. PMID- 25125158 TI - [Centennial retrospective on the evolution and development of nursing research in Taiwan]. AB - Nursing is a distinct branch of science. Nursing research is not only key to developing professional knowledge and but also to promoting nursing as an independent discipline. This paper describes the development and outcomes of nursing research over the past 100 years and then explores the factors that have influenced the focus of nursing research in the past. Findings may be applied to future efforts to promote nursing research. The authors hope that nurses integrate the best research evidence, the best clinical judgment, and the expectations of patients in order to provide the best quality of nursing care through reflection and praxis in nursing research. PMID- 25125159 TI - [Centennial retrospective on the evolution and development of the nursing profession in Taiwan]. AB - This article explores the evolution and development of the Taiwanese nursing profession. After introducing the origins of nursing, this article proceeds to introduce nursing during various periods in Taiwan, including the early-Qing Dynasty, foreign missionary nursing, the Japanese Colonial Era, and the Nationalist Chinese Era following World War Two up to the present. The authors then present the current situation in the Taiwanese nursing profession in terms of gender issues, high-technology developments, educational issues, the nursing licensing examination, hiring and training, multiple role functions, and the skill-mix care model. Finally, the authors make recommendations for the further development and improvement of the nursing profession in Taiwan. PMID- 25125160 TI - [Centennial retrospective on the evolution and development of nursing education in Taiwan]. AB - Nursing education in Taiwan has developed significantly over the past one hundred years. Throughout the first half of the 20th century, nursing education in Taiwan ended at the high school level. However, over the most recent 50 years, this level has been gradually raised, and nursing doctoral programs are now offered today. Changes in the nursing profession over the past century have been influenced by social and political factors, war, the health care policies, and national education policies. Areas of nursing education that have presented key challenges to change and innovation include the nursing faculty, curriculum, teaching materials, and quality of teaching. Today, key future goals for nursing education in Taiwan are: Raising the entry level of generic nursing education from junior high to the high-school level, improving the curricula for master's and doctoral students, cultivating advanced practice nurses, improving the quality of nursing faculties, and establishing a mechanism to ensure the consistent quality of nursing education. PMID- 25125161 TI - [Centennial retrospective on the role expansion of the nursing profession in Taiwan]. AB - Advanced practice nurses were introduced in Taiwan to address increasingly complex public healthcare needs, reimbursement reform in the National Health Care Insurance system, and healthcare organization changes and to ensure high-quality care for patients. This article discusses the role and the function of nurses; the expansion and extension of nursing responsibilities; the specific roles of the advanced practice nurse, the nurse practitioner, the case manager, and the care manager; the affect of advanced practice on nursing identity and effectiveness; and key current issues in advanced practice. Suggestions are provided to improve the professional development of nurses in the future. PMID- 25125162 TI - [A new vision of nursing: the evolution and development of nursing informatics]. AB - Technology development trends in the 21st century are increasingly focused on the development of interdisciplinary applications. Advanced information technology may be applied to integrate nursing care information, simplify nursing processes, and reduce the time spent on work tasks, thereby increasing the amount of time that clinical personnel are available to care for patients and ensuring that patients are provided with high-quality and personalized care services. The development of nursing information began in Taiwan in 2003 and has since expanded and thrived. The ability of nursing information to connect formerly insular national nursing communities promotes the international visibility of Taiwan. The rapid development of nursing information in Taiwan, resulting in the production of informative and outstanding results, has received worldwide attention. The Taiwan Nursing Informatics Association was established in 2006 to nurture nursing information professionals, develop and apply information technology in the health care domain, and facilitate international nursing information exchanges. The association actively promotes nursing information in the areas of administration, education, research, and clinical practice, thereby integrating nursing with empirical applications to enhance the service quality and management of nursing and increase the benefits of nursing teaching and research. To convert information into knowledge, the association develops individualized strategies for managing mobile care and employs an interagency network to exchange and reintegrate resources, establishing active, intelligent nursing based on network characteristics and an empirical foundation. The mid- and long-term objectives of the association involve introducing cloud computing and facilitating the meaningful use of nursing information in both public and government settings, thereby creating a milestone of developing and expanding nursing information unique to Taiwan. PMID- 25125163 TI - [A new vision of nursing: the evolution and development of evidence-based nursing]. AB - The concept and principles of evidence-based medicine (EBM), first introduced in 1996 in the UK and Canada, have greatly impacted healthcare worldwide. Evidence based care is a new approach to healthcare that works to reduce the gap between evidence and practice in order to further the scientific credentials and practices of the nursing profession. The revolution in healthcare has perhaps most noticeably impacted the nursing sciences. Today, new methodologies are increasingly synthesizing knowledge, while expanded access to publication resources is creating a new era in evidence-based nursing. Therefore, we expect to see in Taiwan the increased sharing of innovative implementations of evidence based nursing practice and promotion campaigns and the exploration of a new evidence-based nursing paradigm for incorporating evidence-based concepts into the policymaking process, nursing practice, and nursing education. All scientists in clinical care, education, and research are responsible to establish scientific nursing knowledge in support of the evidence-based nursing practice. PMID- 25125164 TI - Metastatic intramucosal colorectal adenocarcinoma: a case to support review of current concepts (and staging) of early colorectal cancer. PMID- 25125165 TI - Does early identification of low-grade glioma growth impact outcome? PMID- 25125166 TI - Special issue: recent advances in muscle research. PMID- 25125167 TI - Recent advances in muscle research. PMID- 25125168 TI - Memories of Annemarie Weber. PMID- 25125170 TI - The formin FHOD1 in cardiomyocytes. AB - Members of the formin family are known to be involved in the regulation of the actin cytoskeleton. We have recently identified a muscle specific splice variant of the formin FHOD3 and demonstrated its role in the maintenance of the contractile filaments of cardiomyocytes. Here, we characterize the expression and subcellular localization of FHOD3's closest relative, FHOD1, in the heart. Confocal microscopy shows that FHOD1 is mainly located at the intercalated disc, the special type of cell-cell contact between cardiomyocytes, but also partially associated with the myofibrils. Subcellular targeting of FHOD1 is probably mediated by its N-terminal domain, since expression constructs lacking this domain show aberrant localization in primary cultures of neonatal rat cardiomyocytes. Finally, we show that in contrast to FHOD3, FHOD1 shows increased expression levels in dilated cardiomyopathy, suggesting that the two formins play distinct roles and are differentially regulated in cardiomyocytes. PMID- 25125171 TI - Localization of sarcomeric proteins during myofibril assembly in cultured mouse primary skeletal myotubes. AB - It is important to understand how muscle forms normally in order to understand muscle diseases that result in abnormal muscle formation. Although the structure of myofibrils is well understood, the process through which the myofibril components form organized contractile units is not clear. Based on the staining of muscle proteins in avian embryonic cardiomyocytes, we previously proposed that myofibrils formation occurred in steps that began with premyofibrils followed by nascent myofibrils and ending with mature myofibrils. The purpose of this study was to determine whether the premyofibril model of myofibrillogenesis developed from studies developed from studies in avian cardiomyocytes was supported by our current studies of myofibril assembly in mouse skeletal muscle. Emphasis was on establishing how the key sarcomeric proteins, F-actin, nonmuscle myosin II, muscle myosin II, and alpha-actinin were organized in the three stages of myofibril assembly. The results also test previous reports that nonmuscle myosins II A and B are components of the Z-bands of mature myofibrils, data that are inconsistent with the premyofibril model. We have also determined that in mouse muscle cells, telethonin is a late assembling protein that is present only in the Z-bands of mature myofibrils. This result of using specific telethonin antibodies supports the approach of using YFP-tagged proteins to determine where and when these YFP-sarcomeric fusion proteins are localized. The data presented in this study on cultures of primary mouse skeletal myocytes are consistent with the premyofibril model of myofibrillogenesis previously proposed for both avian cardiac and skeletal muscle cells. PMID- 25125172 TI - Translational control of tropomyosin expression in vertebrate hearts. AB - The tropomyosin (TM) gene family produces a set of related TM proteins with important functions in striated and smooth muscle, and nonmuscle cells. In vertebrate striated muscle, the thin filament consists largely of actin, TM, the troponin (Tn) complex (Tn-I, Tn-C and Tn-T), and tropomodulin (Tmod) and is responsible for mediating Ca(2+) control of muscle contraction and relaxation. There are four known genes (designated as TPM1, TPM2, TPM3, and TPM4) for TM in vertebrates. The four TM genes generate a multitude of tissue- and developmental specific isoforms through the use of different promoters, alternative mRNA splicing, different 3'-end mRNA processing and tissue-specific translational control. In this review, we have focused mainly on the regulation of TM expression in striated muscles, primarily in vertebrate hearts with special emphasis on translational control using mouse and Mexican axolotl animal models. PMID- 25125169 TI - Regulation of structure and function of sarcomeric actin filaments in striated muscle of the nematode Caenorhabditis elegans. AB - The nematode Caenorhabditis elegans has been used as a valuable system to study structure and function of striated muscle. The body wall muscle of C. elegans is obliquely striated muscle with highly organized sarcomeric assembly of actin, myosin, and other accessory proteins. Genetic and molecular biological studies in C. elegans have identified a number of genes encoding structural and regulatory components for the muscle contractile apparatuses, and many of them have counterparts in mammalian cardiac and skeletal muscles or striated muscles in other invertebrates. Applicability of genetics, cell biology, and biochemistry has made C. elegans an excellent system to study mechanisms of muscle contractility and assembly and maintenance of myofibrils. This review focuses on the regulatory mechanisms of structure and function of actin filaments in the C. elegans body wall muscle. Sarcomeric actin filaments in C. elegans muscle are associated with the troponin-tropomyosin system that regulates the actin-myosin interaction. Proteins that bind to the side and ends of actin filaments support ordered assembly of thin filaments. Furthermore, regulators of actin dynamics play important roles in initial assembly, growth, and maintenance of sarcomeres. The knowledge acquired in C. elegans can serve as bases to understand the basic mechanisms of muscle structure and function. PMID- 25125174 TI - A Titan but not necessarily a ruler: assessing the role of titin during thick filament patterning and assembly. AB - The sarcomeres of striated muscle are among the most elaborate and dynamic eukaryotic cellular protein machinery, and the mechanisms by which these semicrystalline filament networks are initially patterned and assembled remain contentious. In addition to the acto-myosin filaments that provide motor function, the sarcomere contains titin filaments, comprised of individual molecules of the giant Ig- and fibronectin domain-rich protein titin. Titin is the largest known protein, containing many structurally distinct domains with a variety of proposed functions, including sarcomere stabilization, the prevention of over-stretching, and returning to resting length after contraction. One molecule of titin, which binds to both the Z-disk and the M-line, spans a half sarcomere, and is proposed to serve as a "molecular ruler" that dictates the spacing of sarcomeres. The semirigid rod-like A-band region of titin has also been proposed to act as a scaffold for thick filament formation during muscle development, but despite decades of research, this hypothesis has not been rigorously tested. Recent studies in zebrafish have brought into question the necessity for the A-band region of titin during the early stages of sarcomere patterning. In this review, we give an overview of the many different roles of titin in the development and function of striated muscle, and address the validity of the "molecular ruler" model of myofibrillogenesis in light of the current literature. PMID- 25125173 TI - Expression of myotilin during chicken development. AB - Several missense mutations in the Z-band protein, myotilin, have been implicated in human muscle diseases such as myofibrillar myopathy, spheroid body myopathy, and distal myopathy. Recently, we have reported the cloning of chicken myotilin cDNA. In this study, we have investigated the expression of myotilin in cross striated muscles from developing chicken by qRT-PCR and in situ hybridizations. In situ hybridization of embryonic stages shows myotilin gene expression in heart, somites, neural tissue, eyes and otocysts. RT-PCR and qRT-PCR data, together with in situ hybridization results point to a biphasic transcriptional pattern for MYOT gene during early heart development with maximum expression level in the adult. In skeletal muscle, the expression level starts decreasing after embryonic day 20 and declines in the adult skeletal muscles. Western blot assays of myotilin in adult skeletal muscle reveal a decrease in myotilin protein compared with levels in embryonic skeletal muscle. Our results suggest that MYOT gene may undergo transcriptional activation and repression that varies between tissues in developing chicken. We believe this is the first report of the developmental regulation on myotilin expression in non-mammalian species. PMID- 25125175 TI - Probing muscle ankyrin-repeat protein (MARP) structure and function. AB - Muscle ankyrin-repeat proteins (MARPs) have been shown to serve diverse functions within cardiac and skeletal muscle cells. Apart from their interactions with sarcomeric proteins like titin or myopalladin that locate them along myofilaments, MARPs are able to shuttle to the nucleus where they act as modulators for a variety of transcription factors. The deregulation of MARPs in many cardiac and skeletal myopathies contributes to their use as biomarkers for these diseases. Many of their functions are attributed to their domain composition. MARPs consist of an N-terminal coiled-coil domain responsible for their dimerization. The C-terminus contains a series of ankyrin repeats, whose best-characterized function is to bind to the N2A region of the giant sarcomeric protein titin. Here we investigate the nature of their dimerization and their interaction with titin more closely. We demonstrate that the coiled-coil domain in all MARPs enables their homo- and hetero-dimerization in antiparallel fashion. Protein complementation experiments indicate further antiparallel binding of the ankyrin repeats to titin's N2A region. Binding of MARP to titin also affects its PKA mediated phosphorylation. We demonstrate further that MARPs themselves are phosphorylated by PKA and PKC, potentially altering their structure or function. These studies elucidate structural relationships within the stretch-responsive MARP/titin complex in cross-striated muscle cells, and may relate to disease relevant posttranslational modifications of MARPs and titin that alter muscle compliance. PMID- 25125178 TI - SMYD proteins: key regulators in skeletal and cardiac muscle development and function. AB - Muscle fibers are composed of myofibrils, one of the most highly ordered macromolecular assemblies in cells. Recent studies demonstrate that members of the Smyd family play critical roles in myofibril assembly of skeletal and cardiac muscle during development. The Smyd family consists of five members including Smyd1, Smyd2, Smyd3, Smyd4, and Smyd5. They share two highly conserved structural and functional domains, namely the SET and MYND domains involved in lysine methylation and protein-protein interaction, respectively. Smyd1 is specifically expressed in muscle cells under the regulation of myogenic transcriptional factors of the MyoD and Mef2 families and the serum responsive factor. Loss of function studies reveal that Smyd1 is required for cardiomyogenesis and sarcomere assembly in skeletal and cardiac muscles. Smyd2, on another hand, is dispensable for heart development in mice. However, Smyd2 appears to play a role in myofilament organization in both skeletal and cardiac muscles via Hsp90 methylation. A Drosophila Smyd4 homologue is a muscle-specific transcriptional modulator involved in the development or function of adult muscle. The molecular mechanisms by which Smyd family proteins function in muscle cells are not well understood. It has been suggested that members of the Smyd family may use multiple mechanisms to control muscle development and cell differentiation, including transcriptional regulation, epigenetic regulation via histone methylation, and methylation of proteins other than histones, such as molecular chaperone Hsp90. PMID- 25125176 TI - Protein arginylation, a global biological regulator that targets actin cytoskeleton and the muscle. AB - Posttranslational addition of Arg to proteins, mediated by arginyltransferase ATE1 has been first observed in 1963 and remained poorly understood for decades since its original discovery. Recent work demonstrated the global nature of arginylation and its essential role in multiple physiological pathways during embryogenesis and adulthood and identified over a hundred of proteins arginylated in vivo. Among these proteins, the prominent role belongs to the actin cytoskeleton and the muscle, and follow up studies strongly suggests that arginylation constitutes a novel biological regulator of contractility. This review presents an overview of the studies of protein arginylation that led to the discovery of its major role in the muscle. PMID- 25125180 TI - Structural implications of beta-cardiac myosin heavy chain mutations in human disease. AB - Over 500 disease-causing point mutations have been found in the human beta cardiac myosin heavy chain, many quite recently with modern sequencing techniques. This review shows that clusters of these mutations occur at critical points in the sequence and investigates whether the many studies on these mutants reveal information about the function of this protein. PMID- 25125177 TI - Getting folded: chaperone proteins in muscle development, maintenance and disease. AB - Chaperone proteins are critical for protein folding and stability, and hence are necessary for normal cellular organization and function. Recent studies have begun to interrogate the role of this specialized class of proteins in muscle biology. During development, chaperone-mediated folding of client proteins enables their integration into nascent functional sarcomeres. In addition to assisting with muscle differentiation, chaperones play a key role in the maintenance of muscle tissues. Furthermore, disruption of the chaperone network can result in neuromuscular disease. In this review, we discuss how chaperones are involved in myofibrillogenesis, sarcomere maintenance, and muscle disorders. We also consider the possibilities of therapeutically targeting chaperones to treat muscle disease. PMID- 25125179 TI - Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential. AB - The cardiac sarcomere is the functional unit for myocyte contraction. Ordered arrays of sarcomeric proteins, held in stoichiometric balance with each other, respond to calcium to coordinate contraction and relaxation of the heart. Altered sarcomeric structure-function underlies the primary basis of disease in multiple acquired and inherited heart disease states. Hypertrophic and restrictive cardiomyopathies are caused by inherited mutations in sarcomeric genes and result in altered contractility. Ischemia-mediated acidosis directly alters sarcomere function resulting in decreased contractility. In this review, we highlight the use of acute genetic engineering of adult cardiac myocytes through stoichiometric replacement of sarcomeric proteins in these disease states with particular focus on cardiac troponin I. Stoichiometric replacement of disease causing mutations has been instrumental in defining the molecular mechanisms of hypertrophic and restrictive cardiomyopathy in a cellular context. In addition, taking advantage of stoichiometric replacement through gene therapy is discussed, highlighting the ischemia-resistant histidine-button, A164H cTnI. Stoichiometric replacement of sarcomeric proteins offers a potential gene therapy avenue to replace mutant proteins, alter sarcomeric responses to pathophysiologic insults, or neutralize altered sarcomeric function in disease. PMID- 25125183 TI - Myosin VI localization and expression in striated muscle pathology. AB - Myosin VI (MVI) is a unique unconventional myosin translocating, unlike other myosins, towards the minus end of actin filaments. It is involved in numerous cellular processes such as endocytosis, intracellular trafficking, cell migration, and transcription. In mammalian skeletal muscles it localizes mainly to sarcoplasmic reticulum and is also present within the muscle nuclei and at the neuromuscular junction (Karolczak et al. Histochem Cell Biol 2013; 23:219-228). We have also shown that in denervated rat hindlimb muscle the MVI expression level is significantly increased and its localization is changed, indicating an important role of MVI in striated muscle pathology. Here, we addressed this problem by examining the distribution and expression levels of myosin VI in biopsies of skeletal muscles from patients with different myopathies. We found that, particularly in myopathies associated with fiber atrophy, the amount of MVI was enhanced and its localization in affected fibers was changed. Also, since a mutation within the human MVI gene was shown to be associated with cardiomyopathy, we assessed MVI localization and expression level in cardiac muscle using wild type and MLP(-/-) mice, a dilated cardiomyopathy model. No significant difference in MVI expression level was observed for both types of animals. MVI was found at intercalated discs and also at the sarcoplasmic reticulum. In the knockout mice, it was also present in ring-like structures surrounding the nuclei. The data indicate that in striated muscle MVI could be engaged in sarcoplasmic reticulum maintenance and/or functioning, vesicular transport, signal transmission and possibly in gene transcription. PMID- 25125184 TI - The pathway for force transmission in the rat anococcygeus muscle: a tale of two tendons. AB - Smooth muscles forming the wall of tissues having conduit and reservoir functions (including blood vessels, intestinal tract, and stomach, gall bladder, urinary bladder, respectively) are organized into sheets or layers. The pathway for force transmission emanates from myosin interaction with actin filaments attached to intracellular dense bodies linked by the cytoskeleton to plasma membrane dense bodies which are adhesion sites for the extracellular matrix. The extracellular matrix is continuous throughout and between muscle layers, facilitating their coordinated function. There are a few instances where smooth muscles are organized in small longitudinal bundles with elastic tendinous ends, such as the pilomotor muscles of skin, the ciliary muscle of the eye, and costo-uterine muscle. In this study, we examine ultrastructure of two tendons that tether the anococcygeus muscle of the rat from the spine to the colon, the former a true tendon (myotendinous junction) and the latter a layer of connective tissue (intramuscular tendon). These regions show morphological specializations in the distribution and thickness of dense bodies, basement membrane, fiber shape and quantity of extracellular matrix. At the plasma membrane between dense bodies are caveolae, flask shaped structures primarily responsible for signal transduction, proliferation and electromechanical coupling. Changes also occur in caveolar regions, where the basement membrane is thickened and attachments to extracellular matrix are seen. Together, both regions of the plasma membrane are designed to facilitate force transmission. PMID- 25125181 TI - Understanding cardiac sarcomere assembly with zebrafish genetics. AB - Mutations in sarcomere genes have been found in many inheritable human diseases, including hypertrophic cardiomyopathy. Elucidating the molecular mechanisms of sarcomere assembly shall facilitate understanding of the pathogenesis of sarcomere-based cardiac disease. Recently, biochemical and genomic studies have identified many new genes encoding proteins that localize to the sarcomere. However, their precise functions in sarcomere assembly and sarcomere-based cardiac disease are unknown. Here, we review zebrafish as an emerging vertebrate model for these studies. We summarize the techniques offered by this animal model to manipulate genes of interest, annotate gene expression, and describe the resulting phenotypes. We survey the sarcomere genes that have been investigated in zebrafish and discuss the potential of applying this in vivo model for larger scale genetic studies. PMID- 25125186 TI - Tenascin-C in development and disease of blood vessels. AB - Tenascin-C (TNC) is an extracellular glycoprotein categorized as a matricellular protein. It is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion, and has a wide range of effects on cell response in tissue morphogenesis and remodeling including the cardiovascular system. In the heart, TNC is sparsely detected in normal adults but transiently expressed at restricted sites during embryonic development and in response to injury, playing an important role in myocardial remodeling. Although TNC in the vascular system appears more complex than in the heart, the expression of TNC in normal adult blood vessels is generally low. During embryonic development, vascular smooth muscle cells highly express TNC on maturation of the vascular wall, which is controlled in a way that depends on the embryonic site of cell origin. Strong expression of TNC is also linked with several pathological conditions such as cerebral vasospasm, intimal hyperplasia, pulmonary artery hypertension, and aortic aneurysm/ dissection. TNC synthesized by smooth muscle cells in response to developmental and environmental cues regulates cell responses such as proliferation, migration, differentiation, and survival in an autocrine/paracrine fashion and in a context-dependent manner. Thus, TNC can be a key molecule in controlling cellular activity in adaptation during normal vascular development as well as tissue remodeling in pathological conditions. PMID- 25125182 TI - Finding the sweet spot: assembly and glycosylation of the dystrophin-associated glycoprotein complex. AB - The dystrophin-associated glycoprotein complex (DGC) is a collection of glycoproteins that are essential for the normal function of striated muscle and many other tissues. Recent genetic studies have implicated the components of this complex in over a dozen forms of muscular dystrophy. Furthermore, disruption of the DGC has been implicated in many forms of acquired disease. This review aims to summarize the current state of knowledge regarding the processing and assembly of dystrophin-associated proteins with a focus primarily on the dystroglycan heterodimer and the sarcoglycan complex. These proteins form the transmembrane portion of the DGC and undergo a complex multi-step processing with proteolytic cleavage, differential assembly, and both N- and O-glycosylation. The enzymes responsible for this processing and a model describing the sequence and subcellular localization of these events are discussed. PMID- 25125185 TI - Smooth muscle-protein translocation and tissue function. AB - Smooth muscle (SM) tissue is a complex organization of multiple cell types and is regulated by numerous signaling molecules (neurotransmitters, hormones, cytokines, etc.). SM contractile function can be regulated via expression and distribution of the contractile and cytoskeletal proteins, and activation of any of the second messenger pathways that regulate them. Spatial-temporal changes in the contractile, cytoskeletal or regulatory components of SM cells (SMCs) have been proposed to alter SM contractile activity. Ca(2+) sensitization/desensitization can occur as a result of changes at any of these levels, and specific pathways have been identified at all of these levels. Understanding when and how proteins can translocate within the cytoplasm, or to and-from the plasmalemma and the cytoplasm to alter contractile activity is critical. Numerous studies have reported translocation of proteins associated with the adherens junction and G protein-coupled receptor activation pathways in isolated SMC systems. Specific examples of translocation of vinculin to and from the adherens junction and protein kinase C (PKC) and 17 kDa PKC-potentiated inhibitor of myosin light chain phosphatase (CPI-17) to and from the plasmalemma in isolated SMC systems but not in intact SM tissues are discussed. Using both isolated SMC systems and SM tissues in parallel to pursue these studies will advance our understanding of both the role and mechanism of these pathways as well as their possible significance for Ca(2+) sensitization in intact SM tissues and organ systems. PMID- 25125188 TI - Is sarcomere lattice geometry optimal? Analysis of several potential virtual polygon cross-sectional patterns for actin and myosin myofilaments in muscle. AB - The hexagonal arrangement of actin filaments in skeletal muscle is not the fundamental geometrical or functioning myofilament unit. This analysis of several possible sarcomere lattice geometries for the arrangement of the actin and myosin filaments identifies several geometrical constraints that can be compared for their effect on muscle sarcomere functioning and efficiency. Three distinct virtual polygons, with myosins at their vertices and that tessellate the plane, are compared for both centered actin and perimeter actin arrangements. The analysis evaluates the optimal ratio of myosin to actin filaments, the packing density, and the effect on new myofilament formation in muscle hypertrophy for the various lattice geometries. The results support the view that no single measure of geometrical effectiveness can evaluate definitively the efficiency of any particular arrangement of the myofilaments. The analysis provides quantitative measures of several parameters that, taken overall, support the effectiveness of the myofilament arrangement in Nature. It provides a new definition of the fundamental myofilament unit (FMU). It is possible to calculate the number of actin and myosin myofilaments that need to be added to each polygon arrangement of the myofilaments to create a new FMU for that specific geometry. This leads to useful conclusions about the biochemical efficiency involved in where such units arise in the course of muscle hypertrophy. It supports the idea that the evolutionary endpoint for optimizing muscle's force-generating function can be better understood via the concepts of a FMU and the polygon arrangement of the sarcomere lattice geometry. PMID- 25125189 TI - Myosin VIIA is a marker for the cone accessory outer segment in zebrafish. AB - The accessory outer segment, a cytoplasmic structure running alongside the photoreceptor outer segment, has been described in teleost fishes, excluding the model organism zebrafish. So far, the function of the accessory outer segment is unknown. Here, we describe the ultrastructure of the zebrafish cone accessory outer segment by electron microscopy. Starting at the connecting cilium, the accessory outer segment runs parallel alongside the cone outer segment (COS). A thin plasma bridge connects the outer segment with the accessory outer segment, whose surface is enlarged by foldings and invaginations. Beside the morphological descriptions, we demonstrate that the Usher protein myosin VIIa (Myo7a) is a specific marker for the zebrafish cone accessory outer segment. Zebrafish cone photoreceptors possess a large and well-differentiated accessory outer segment, in which the unconventional motor protein Myo7a is highly enriched. The direct cytoplasmic contact with the COS as well as the surface enlargement of the accessory outer segment suggests an important role of this structure in transport and exchange of metabolites between the COS and the surrounding retinal pigment epithelium. In future studies of the outer retina, more attention should be paid to this often neglected structure. PMID- 25125191 TI - Pre-clinical research in small animals using radiotherapy technology--a bidirectional translational approach. AB - For translational cancer research, pre-clinical in-vivo studies using small animals have become indispensable in bridging the gap between in-vitro cell experiments and clinical implementation. When setting up such small animal experiments, various biological, technical and methodical aspects have to be considered. In this work we present a comprehensive topical review based on relevant publications on irradiation techniques used for pre-clinical cancer research in mice and rats. Clinical radiotherapy treatment devices for the application of external beam radiotherapy and brachytherapy as well as dedicated research irradiation devices are feasible for small animal irradiation depending on the animal model and the experimental goals. In this work, appropriate solutions for the technological transfer of human radiation oncology to small animal radiation research are summarised. Additionally, important information concerning the experimental design is provided such that reliable and clinically relevant results can be attained. PMID- 25125187 TI - The role of mechanotransduction on vascular smooth muscle myocytes' [corrected] cytoskeleton and contractile function. AB - Smooth muscle (SM) exhibits a highly organized structural hierarchy that extends over multiple spatial scales to perform a wide range of functions at the cellular, tissue, and organ levels. Early efforts primarily focused on understanding vascular SM (VSM) function through biochemical signaling. However, accumulating evidence suggests that mechanotransduction, the process through which cells convert mechanical stimuli into biochemical cues, is requisite for regulating contractility. Cytoskeletal proteins that comprise the extracellular, intercellular, and intracellular domains are mechanosensitive and can remodel their structure and function in response to external mechanical cues. Pathological stimuli such as malignant hypertension can act through the same mechanotransductive pathways to induce maladaptive remodeling, leading to changes in cellular shape and loss of contractile function. In both health and disease, the cytoskeletal architecture integrates the mechanical stimuli and mediates structural and functional remodeling in the VSM. PMID- 25125192 TI - Improving perfusion quantification in arterial spin labeling for delayed arrival times by using optimized acquisition schemes. AB - OBJECTIVE: The improvement in Arterial Spin Labeling (ASL) perfusion quantification, especially for delayed bolus arrival times (BAT), with an acquisition redistribution scheme mitigating the T1 decay of the label in multi TI ASL measurements is investigated. A multi inflow time (TI) 3D-GRASE sequence is presented which adapts the distribution of acquisitions accordingly, by keeping the scan time constant. MATERIAL AND METHODS: The MR sequence increases the number of averages at long TIs and decreases their number at short TIs and thus compensating the T1 decay of the label. The improvement of perfusion quantification is evaluated in simulations as well as in-vivo in healthy volunteers and patients with prolonged BATs due to age or steno-occlusive disease. RESULTS: The improvement in perfusion quantification depends on BAT. At healthy BATs the differences are small, but become larger for longer BATs typically found in certain diseases. The relative error of perfusion is improved up to 30% at BATs>1500ms in comparison to the standard acquisition scheme. CONCLUSION: This adapted acquisition scheme improves the perfusion measurement in comparison to standard multi-TI ASL implementations. It provides relevant benefit in clinical conditions that cause prolonged BATs and is therefore of high clinical relevance for neuroimaging of steno-occlusive diseases. PMID- 25125193 TI - Bacteria-mediated aerobic degradation of hexacosane in vitro conditions. AB - In vitro degradation of hexacosane (C26H54), a HMW n-alkane, was studied in MSM by two bacterial strains i.e., Pseudomonas sp. BP10 and Stenotrophomonas nitritireducens E9, isolated from petroleum sludge, in isolation and combination. The results revealed that both the strains were able to metabolize hexacosane by 82% in isolation and 98% in their consortium after 7days. An enhancement of 16% in hexacosane degradation by the consortium indicated an additive action of bacterial strains. However, in control, a degradation of 21% was attributed to abiotic factors. During incubation with hexacosane, both the bacteria continued to multiply in isolation and consortium, which reflected that hexacosane was utilized by bacteria as a carbon and energy source. Activities of alkane hydroxylase and alcohol dehydrogenase were differentially expressed in isolation and combination, indicating their involvement in hexacosane degradation. Enhanced cell surface hydrophobicity and emulsification index and reduced surface tension also supported the degradation process. PMID- 25125194 TI - Biodiesel from wet microalgae: extraction with hexane after the microwave assisted transesterification of lipids. AB - A chloroform-free novel process for the efficient production of biodiesel from wet microalgae is proposed. Crude biodiesel is produced through extraction with hexane after microwave-assisted transesterification (EHMT) of lipids in wet microalgae. Effects of different parameters, including reaction temperature, reaction time, methanol dosage, and catalyst dosage, on fatty acids methyl esters (FAMEs) yield are investigated. The yield of FAME extracted into the hexane from the wet microalgae is increased 6-fold after the transesterification of lipids. The yield of FAME obtained through EHMT of lipids in wet microalgae is comparable to that obtained through direct transesterification of dried microalgae biomass with chloroform; however, FAME content in crude biodiesel obtained through EHMT is 86.74%, while that in crude biodiesel obtained through the chloroform-based process is 75.93%. EHMT ensures that polar pigments present in microalgae are not extracted into crude biodiesel, which leads to a 50% reduction in nitrogen content in crude biodiesel. PMID- 25125195 TI - Characterization of corncob-derived biochar and pyrolysis kinetics in comparison with corn stalk and sawdust. AB - In this study, thermal and physicochemical characterization results of corncob (CC) and its derived biochars were analyzed and differentiated from sawdust (SD) and cornstalk (CS). The pyrolysis temperature shows the largest effect on the yield of biochar produced compare with residing time, heating rate, and feedstock particle size. The CC-derived biochars produced at temperatures ranging from 300 to 600 degrees C were analyzed. The CC was thermochemically altered to a stable biochar when the pyrolysis temperature was set to over 500 degrees C. To deduce the reaction mechanism of the CC during the major thermal decomposition stage, 16 mechanisms in solid-state reactions were applied. The reaction order and nucleation mechanisms described the thermal decomposition of the CC. By using the best-fitted mechanisms, the kinetic parameters were calculated. The weight active energy of the CC was 122.42kJ/mol, which was the lowest value compared to those of CS and SD. PMID- 25125196 TI - Biocapture of CO2 from biogas by oleaginous microalgae for improving methane content and simultaneously producing lipid. AB - This study aimed to use oleaginous microalgae to capture CO2 from biogas for improving methane content and simultaneously producing lipid. Several microalgae were screened for their ability to grow and produce lipid using CO2 in biogas. A marine Chlorella sp. was the most suitable strain for capturing CO2 and producing lipid using biogas (50% v/v CO2 in methane) as well as using 50% v/v CO2 in air. The medium and operating conditions were optimized through response surface methodology (RSM). The optimal concentrations of KNO3 and K2HPO4 were 0.80gL(-1) and 0.06gL(-1), respectively. The optimal operating conditions were: initial pH of 7.8, initial cell concentration of 10(7.5)cellsmL(-1), light intensity of 4500lux and gas flow rate of 0.03Lmin(-1). After optimization, 89.3% of CO2 was removed from biogas and the methane content was increased up to 94.7%. The lipid productivity was 94.7mgL(-1)day(-1). PMID- 25125197 TI - Application of hydrothermal treatment to affect the fermentability of Pinus radiata pulp mill effluent sludge. AB - A hybrid technique incorporating a wet oxidation stage and secondary fermentation step was used to process Pinus radiata pulp mill effluent sludge. The effect of hydrothermal oxidation at high temperature and pressure on the hydrolysis of constituents of the waste stream was studied. Biochemical acidogenic potential assays were conducted to assess acid production resulting from anaerobic hydrolysis of the wet oxidised hydrolysate under acidogenic conditions. Significant degradation of the lignin, hemicellulose, suspended solids, carbohydrates and extractives were observed with wet oxidation. In contrast, cellulose showed resistance to degradation under the experimental conditions. Extensive degradation of biologically inhibitory compounds by wet oxidation did not show a beneficial impact on the acidogenic or methanogenic potential compared to untreated samples. PMID- 25125198 TI - High cell density lipid rich cultivation of a novel microalgal isolate Chlorella sorokiniana FC6 IITG in a single-stage fed-batch mode under mixotrophic condition. AB - A single-stage mixotrophic cultivation strategy was developed with a novel microalgal isolate Chlorella sorokiniana FC6 IITG for high cell density lipid rich biomass generation. The strain was evaluated for growth and lipid content under different physico-chemical parameters, nutritional conditions and trophic modes. Finally, a single-stage mixotrophic fed-batch cultivation strategy was demonstrated with intermittent feeding of key nutrients along with dynamic increase in light intensity for high cell density biomass and sodium acetate as elicitor for lipid enrichment. The key findings: (i) glucose and sodium acetate was identified as growth supporting and lipid inducing nutrients, respectively; (ii) mixotrophic batch cultivation resulted in maximum biomass and lipid productivity (mgL(-1)day(-1)) of 455.5 and 111.85, respectively; (iii) single stage mixotrophic fed-batch cultivation showed maximum biomass productivity of 1.93gL(-1)day(-1) (biomass titer 15.81gL(-1)) and lipid productivity of 550mgL( 1)day(-1); (iv) biodiesel properties were in accordance with international standards. PMID- 25125199 TI - Brait-Fahn-Schwarz disease: the missing link between ALS and Parkinson's disease. PMID- 25125200 TI - Topographic determinants of mobile vertebrate predator hotspots: current knowledge and future directions. AB - Despite being identified as a driver of mobile predator aggregations (hotspots) in both marine and terrestrial environments, topographic complexity has long remained a challenging concept for scientists to visualise and a difficult parameter to estimate. It is only with the advent of high-speed computers and the recent popularisation of geographical information systems (GIS) that terrain attributes have begun to be quantitatively measured in three-dimensional space and related to wildlife dynamics, making the well-established field of geomorphometry (or 'digital terrain modelling') a discipline of growing appeal to biologists. Although a diverse array of numerical metrics is now available to describe the shape, geometry and physical properties of natural habitats, few of these are known to, or adequately used by, ecologists. In this review, we examine the nature and usage of 56 geomorphometrics extracted from the ecological modelling literature over a period of 32 years (1979-2011). We show that, in studies of mobile predators, numerous topographic variables have largely been overlooked in favour of single basic metrics that do not, on their own, fully capture the complexity of continuous landscapes. Based on a simulation approach, we assess the redundancy and correlation structure of these metrics and demonstrate that a majority are highly collinear. We highlight a suite of 7-8 complementary metrics which best explain topographic patterns across a bathymetric grid of the west Australian seafloor, and contend that field and analytical protocols should prioritise variables of these types, particularly when the responses of predator populations to physical habitat features are of interest. We suggest that prominent structures such as canyons, seamounts or mountain chains can serve as useful proxies for predator hotspots, especially in remote locations where access to high-resolution biological data is often limited. PMID- 25125201 TI - Minimally invasive surgical instruments with an accessory channel capable of integrating fibre-optic cable for optical biopsy: a review of the state of the art. AB - This review article provides a comprehensive overview and classification of minimally invasive surgical instruments with an accessory channel incorporating fibreoptics or another auxiliary device for various purposes. More specifically, this review was performed with the focus on the newly emerging field of optical biopsy, its objective being to discuss primarily the instruments capable of carrying out the optical biopsy and subsequent tissue resection. Instruments housing the fibreoptics for other uses, as well as instruments with an accessory channel capable of housing the fibreoptics instead of their original auxiliary device after relevant design modifications, supplement the review. The entire Espacenet and Scopus databases were searched, yielding numerous patents and articles on conceptual and existing instruments satisfying the criteria. The instruments were categorised based on the function the fibreoptics or the auxiliary device serves. On the basis of their geometrical placement with respect to the tissue resector or manipulator, the subcategories were further defined. This subdivision was used to identify the feasibility of performing the optical biopsy and the tissue resection in an accurate and successive fashion. In general, the existing concepts or instruments are regarded as limited with regard to such a functionality, either due to the placement of their accessory channel with or without the fibreoptics or due to the operational restrictions of their tissue manipulators. A novel opto-mechanical biopsy harvester, currently under development at Delft University of Technology, is suggested as a promising alternative, ensuring a fast and accurate succession of the optical and the mechanical biopsies of a flat superficial tissue. PMID- 25125203 TI - Computational study of van der Waals complexes between borylenes and hydrocarbons. AB - The addition of borylenes (RB) to prototypical carbon-carbon multiple bonds (ethyne, ethene) and the insertion into a C-H bond of methane involves weakly bound van der Waals complexes of the reaction partners according to computational chemistry methods. Geometries of all complexes were optimized using spin component scaled second-order Moller-Plesset perturbation theory (SCS-MP2) in combination with a quadruple-zeta (def2-QZVP) basis set. Energies were further refined using the coupled-cluster (CCSD(T)) method in combination with basis sets up to quadruple-zeta quality (def2-QZVP and aug-cc-pVTZ). All of the complexes of borylenes studied correspond to shallow minima on their potential-energy surfaces. Borylene complexes with ethyne are the most stable and those with methane are the least stable ones. Aminoborylene complexes BNHR with ethyne and ethene are stabilized mainly by NH???pi interactions. Symmetry-adapted perturbation theory (SAPT) was performed to analyze the nature of the interaction between borylene molecules and hydrocarbons. Most of the ethyne complexes are dominated by electrostatic interactions, whereas for most of the ethene and all of the methane complexes the interaction is mainly dispersive. PMID- 25125202 TI - Peptide receptor chemoradionuclide therapy in small cell carcinoma: from bench to bedside. AB - PURPOSE: Small cell cancers (SmCC), whether pulmonary (SCLC) or extrapulmonary, have a poor prognosis unless localised at diagnosis. Given a proportion of these cancers express somatostatin receptor subtype 2 (SSTR2), we aimed to investigate the efficacy of targeted peptide receptor chemoradionuclide therapy (PRCRT). METHODS: In this preclinical study, we used a SCLC xenograft mouse model with high expression of SSTR2 to investigate the effect of peptide receptor radionuclide therapy (PRRT) with chemotherapy compared to either alone. We subsequently explored the clinical utility in a patient with SmCC with high SSTR expression treated with PRCRT. RESULTS: Robust expression of SSTR2 in NCI-H69 SCLC xenografts was documented by (68)Ga-DOTA-octreotate (GaTate) (tumour to background uptake ratio = 35). The combination of PRRT using (177)Lu-DOTA octreotate (LuTate) with carboplatin/etoposide (C/E) chemotherapy was more effective than either LuTate or C/E alone for regression of the NCI-H69 model (p value < 0.05). PRCRT was associated with significantly prolonged survival versus PRRT (p value = 0.0001) or chemotherapy alone (p value = 0.0058). In the subsequent case study, a patient with relapsed SmCC with high SSTR2 expression on GaTate PET underwent PRCRT with radiosensitising etoposide with evidence of a complete metabolic response for 4 months. CONCLUSION: Given the limited treatment options in this setting, PRCRT is a promising therapeutic option for SSTR2 expressing SmCC. PMID- 25125204 TI - Rationally synthesized five-fold twinned core-shell Pt3Ni@Rh nanopentagons, nanostars and nanopaddlewheels for selective reduction of a phenyl ring of phthalimide. AB - Surface-energy fine-tuned five-fold twinned nanostructures with a core-shell Pt3Ni@Rh structural motif, namely, a core-shell Pt3Ni@Rh pentagon, a core-shell Pt3Ni@Rh starfish, and a paddlewheel with a Pt3Ni crankshaft and two Rh five-fold starfish wheels, are prepared by rationally designed stepwise heteroepitaxial growth. Unusual selective hydrogenation of the phenyl ring in phthalimide is accomplished with moderately active core-shell Pt3Ni@Rh pentagons and starfish like nanoparticles. The most active paddlewheel structure proceeds to further reduce one carbonyl group, indicating the sequential nature of phthalimide reduction by Rh nanoparticle catalysis. PMID- 25125205 TI - Hypothermia and operative mortality during on-pump coronary artery bypass grafting. AB - OBJECTIVE: Controversy surrounds the effect of hypothermia on operative mortality during cardiac surgery. The present study accessed a large clinical database of coronary artery bypass graft operations to address the issue. METHODS: A retrospective review of the Society of Thoracic Surgeons Adult Cardiac Surgery Database identified patients treated with isolated, nonemergency, on-pump coronary artery bypass grafting from July 2011 to December 2012. The patients were divided into 3 groups according to their lowest core temperature during the procedure: moderate hypothermia (<= 34 degrees C), mild hypothermia (>34 degrees C but <= 36 degrees C), and normothermia (>36 degrees C). The primary endpoint of the study was operative mortality, defined according to the Database criteria. RESULTS: During the study period, 142,541 patients were available for analysis; 94,777 (66.5%) received moderate hypothermia, 42,750 (30.3%) mild hypothermia, and 5014 (3.5%) normothermia. Operative mortality occurred in 1394 patients (1.5%) in the moderate hypothermia, 534 (1.3%) in the mild hypothermia, and 105 (2.1%) in the normothermia group. Multivariate analysis identified hypothermia (both mild [odds ratio, 0.66; 95% confidence interval, 0.54-0.81; P < .0001] and moderate [odds ratio, 0.73; 95% confidence interval, 0.60-0.89; P = .0015]) was protective against operative mortality compared with normothermia. No incremental benefit was noted between the different hypothermia grades (P = .0827). CONCLUSIONS: Most patients receive hypothermia during on-pump coronary artery bypass grafting. Hypothermia is protective against operative mortality compared with normothermia in such patients. Moderate hypothermia does not provide additional survival benefit. PMID- 25125208 TI - Successful aortic valve repair after trauma-induced aortic regurgitation. PMID- 25125207 TI - Pilot study of pulmonary arterial branch sealing using energy devices in an ex vivo model. AB - OBJECTIVE: Vascular endostaplers are bulky and can be dangerous when dividing small pulmonary arterial (PA) branch vessels during video-assisted thoracoscopic lobectomy. We aimed to evaluate and compare the immediate efficacy of modern energy sealing devices in an ex vivo PA sealing model. METHODS: Patients undergoing anatomical lung resection or lung transplantation were recruited for a prospective cohort pilot study. Four devices were evaluated: Harmonic Ace (Ethicon, Cincinnati, Ohio), Thunderbeat (Olympus, Tokyo, Japan), LigaSure (Covidien, Boulder, Colo), and Enseal (Ethicon; Cincinnati, Ohio). After anatomical lung resection, the PA branches were dissected in vitro. Sealing was then performed with 1 of the sealing devices, the vessel was slowly pressurized, and the bursting pressure was recorded. RESULTS: Forty-nine PA branches were sealed in 14 patients. The mean PA branch diameter was 7.4 mm (1.8-14.5 mm). Ten patients had normal PA pressure and 3 had PA hypertension. The mean bursting pressure in each was as follows: Harmonic Ace group, 415.5 mm Hg (137.1-1388.4 mm Hg), Thunderbeat group, 875 mm Hg (237.1-2871.3 mm Hg); LigaSure group, 214.7 mm Hg (0-579.6 mm Hg); Enseal group, 133.7 mm Hg (0-315.38 mm Hg). There were 2 complete sealing failures: LigaSure (diameter 6.78 mm) and Enseal (diameter 8.3 mm). CONCLUSIONS: In this pilot study to examine energy sealing of PA branches in a simulated ex vivo model, vascular sealing using energy was effective and was able to sustain high intraluminal bursting pressures. Further research is needed to determine the in vivo and long-term safety of PA branch energy sealing. PMID- 25125206 TI - Contemporary outcomes of complete atrioventricular septal defect repair: analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. AB - OBJECTIVE: Contemporary outcomes data for complete atrioventricular septal defect (CAVSD) repair are limited. We sought to describe early outcomes of CAVSD repair across a large multicenter cohort, and explore potential associations with patient characteristics, including age, weight, and genetic syndromes. METHODS: Patients in the Society of Thoracic Surgeons Congenital Heart Surgery Database having repair of CAVSD (2008-2011) were included. Preoperative, operative, and outcomes data were described. Univariate associations between patient factors and outcomes were described. RESULTS: Of 2399 patients (101 centers), 78.4% had Down syndrome. Median age at surgery was 4.6 months (interquartile range, 3.5-6.1 months), with 11.8% (n = 284) aged <= 2.5 months. Median weight at surgery was 5.0 kg (interquartile range, 4.3-5.8 kg) with 6.3% (n = 151) < 3.5 kg. Pulmonary artery band removal at CAVSD repair was performed in 122 patients (4.6%). Major complications occurred in 9.8%, including permanent pacemaker implantation in 2.7%. Median postoperative length of stay (PLOS) was 8 days (interquartile range, 5-14 days). Overall hospital mortality was 3.0%. Weight < 3.5 kg and age <= 2.5 months were associated with higher mortality, longer PLOS, and increased frequency of major complications. Patients with Down syndrome had lower rates of mortality and morbidities than other patients; PLOS was similar. CONCLUSIONS: In a contemporary multicenter cohort, most patients with CAVSD have repair early in the first year of life. Prior pulmonary artery band is rare. Hospital mortality is generally low, although patients at extremes of low weight and younger age have worse outcomes. Mortality and major complication rates are lower in patients with Down syndrome. PMID- 25125209 TI - Results of type II hybrid arch repair with zone 0 stent graft deployment for complex aortic arch pathology. AB - OBJECTIVE: To review the early results of a less invasive, single-stage hybrid arch procedure involving replacement of the ascending aorta, arch debranching, and zone 0 antegrade stent graft deployment. METHODS: Between May 2007 and January 2012, 20 patients with both acute and chronic aortic pathology were managed at 2 institutions with a type 2 hybrid arch procedure. Indications included diffuse atherosclerotic aneurysm, false lumen expansion of chronic aortic dissections, penetrating atherosclerotic ulcer, and acute type A dissection. Mean age was 67 +/- 16.8 years with a mean European System for Cardiac Operative Risk Evaluation II score of 29.5 +/- 19.4. Postoperative clinical and imaging follow-up was complete to a mean 18.5 +/- 15.3 months. RESULTS: Successful zone 0 stent graft deployment was achieved in all cases. There was 1 in-hospital mortality (5%). A second death occurred at 40 days postoperation. Other complications included a permanent neurologic deficit in 1 patient (5%), transient paraplegia in 4 patients (20%), and 3 patients had respiratory complications (15%). There were no cases of renal failure requiring dialysis. Stent-related complications were identified in 4 patients (20%), including 3 type I endoleaks, none of which were at zone 0. There was 1 type II endoleak and a case of stent infolding. Two patients required a second successful endografting procedure. CONCLUSIONS: This single-stage hybrid arch procedure offers an alternative approach to complex diffuse aortic pathology involving the arch. Replacement of the ascending aorta provides a safe location for zone 0 stent graft deployment, eliminating complications of proximal deployment in a native diseased aorta. PMID- 25125211 TI - Solid self-emulsifying phospholipid suspension (SSEPS) with diatom as a drug carrier. AB - We report the application of diatom as a solid carrier for water insoluble drugs applied in oral drug delivery system based on the self-emulsifying drug delivery system (SEDDS) caprylocaproyl macrogol-8 glycerides/lecithin/propylene glycol/caprylic/capric triglyceride. Diatoms are fossilized skeletons of photosynthetic algae with complex 3-dimensional (3D), porous structure consisting of amorphous silica, obtained by purification of diatomaceous earth. Different solid samples of carbamazepine (CBZ) suspension in SEDDS, called solid self emulsifying phospholipid suspension (SSEPS), were prepared using two methods: adsorption of CBZ dispersion in SEDDS by gentle mixing with diatoms in mortar with pestle (Method A) or dispersion of diatoms in ethanol solution of CBZ and SEDDS components, followed by ethanol evaporation (Method B). Release rate of CBZ from SSEPS was significantly higher in comparison to pure drug, physical mixture of diatoms and CBZ as well as solid dispersion of pure CBZ and diatoms obtained by ethanol evaporation. The dissolution of CBZ from SSEPS sample prepared using method B was faster than from the sample prepared by the method A. Higher dissolution for sample prepared by the method B can be attributed to the partial adsorption (deeper localization) of liquid material inside the pores of diatoms. Upon storage of the samples under accelerated conditions (40 degrees C and 70% RH) for 10 weeks no significant changes in CBZ crystallinity and dissolution was in case of SSEPS, contrary to solid dispersion with increased crystallinity, indicating that diatoms with adsorbed liquid CBZ-loaded SEPS can maintain initial CBZ characteristics. PMID- 25125212 TI - Systematic review to identify and appraise outcome measures used to evaluate childhood obesity treatment interventions (CoOR): evidence of purpose, application, validity, reliability and sensitivity. AB - BACKGROUND: Lack of uniformity in outcome measures used in evaluations of childhood obesity treatment interventions can impede the ability to assess effectiveness and limits comparisons across trials. OBJECTIVE: To identify and appraise outcome measures to produce a framework of recommended measures for use in evaluations of childhood obesity treatment interventions. DATA SOURCES: Eleven electronic databases were searched between August and December 2011, including MEDLINE; MEDLINE In-Process and Other Non-Indexed Citations; EMBASE; PsycINFO; Health Management Information Consortium (HMIC); Allied and Complementary Medicine Database (AMED); Global Health, Maternity and Infant Care (all Ovid); Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost); Science Citation Index (SCI) [Web of Science (WoS)]; and The Cochrane Library (Wiley) - from the date of inception, with no language restrictions. This was supported by review of relevant grey literature and trial databases. REVIEW METHODS: Two searches were conducted to identify (1) outcome measures and corresponding citations used in published childhood obesity treatment evaluations and (2) manuscripts describing the development and/or evaluation of the outcome measures used in the childhood intervention obesity evaluations. Search 1 search strategy (review of trials) was modelled on elements of a review by Luttikhuis et al. (Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP, et al. Interventions for treating obesity in children. Cochrane Database Syst Rev 2009;1:CD001872). Search 2 strategy (methodology papers) was built on Terwee et al.'s search filter (Terwee CB, Jansma EP, Riphagen II, de Vet HCW. Development of a methodological PubMed search filter for finding studies on measurement properties of measurement instruments. Qual Life Res 2009;18:1115-23). Eligible papers were appraised for quality initially by the internal project team. This was followed by an external appraisal by expert collaborators in order to agree which outcome measures should be recommended for the Childhood obesity Outcomes Review (CoOR) outcome measures framework. RESULTS: Three hundred and seventy-nine manuscripts describing 180 outcome measures met eligibility criteria. Appraisal of these resulted in the recommendation of 36 measures for the CoOR outcome measures framework. Recommended primary outcome measures were body mass index (BMI) and dual-energy X-ray absorptiometry (DXA). Experts did not advocate any self-reported measures where objective measurement was possible (e.g. physical activity). Physiological outcomes hold potential to be primary outcomes, as they are indicators of cardiovascular health, but without evidence of what constitutes a minimally importance difference they have remained as secondary outcomes (although the corresponding lack of evidence for BMI and DXA is acknowledged). No preference-based quality-of-life measures were identified that would enable economic evaluation via calculation of quality-adjusted life-years. Few measures reported evaluating responsiveness. LIMITATIONS: Proposed recommended measures are fit for use as outcome measures within studies that evaluate childhood obesity treatment evaluations specifically. These may or may not be suitable for other study designs, and some excluded measures may be more suitable in other study designs. CONCLUSIONS: The CoOR outcome measures framework provides clear guidance of recommended primary and secondary outcome measures. This will enhance comparability between treatment evaluations and ensure that appropriate measures are being used. Where possible, future work should focus on modification and evaluation of existing measures rather than development of tools de nova. In addition, it is recommended that a similar outcome measures framework is produced to support evaluation of adult obesity programmes. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 25125214 TI - Direct superior tibiofibular joint arthrography demonstrates consistent communication with the tibiofemoral joint. PMID- 25125213 TI - Embolus characterization in branch retinal artery occlusion by optical coherence tomography. PMID- 25125210 TI - Single genome analysis reveals genetic characteristics of Neuroadaptation across HIV-1 envelope. AB - BACKGROUND: The widespread use of highly effective, combination antiretroviral therapy (cART) has led to a significant reduction in the incidence of HIV associated dementia (HAD). Despite these advances, the prevalence of HIV-1 associated neurocognitive disorders (HANDs) has been estimated at approximately 40%-50%. In the cART era, the majority of this disease burden is represented by asymptomatic neurocognitive impairment and mild neurocognitive disorder (ANI and MND respectively). Although less severe than HAD, these diagnoses carry with them substantial morbidity. RESULTS: In this cross-sectional study, single genome amplification (SGA) was used to sequence 717 full-length HIV-1 envelope (env) clade B variants from the paired cerebrospinal fluid (CSF) and blood plasma samples of fifteen chronically infected HIV-positive individuals with normal neurocognitive performance (NCN), ANI and MND. Various degrees of compartmentalization were found across disease states and history of cART utilization. In individuals with compartmentalized virus, mean HIV-1 env population diversity was lower in the CSF than plasma-derived variants. Overall, mean V1V2 loop length was shorter in CSF-derived quasispecies when compared to contemporaneous plasma populations, and this was found to correlate with a lower mean number of N-linked glycosylation sites in this region. A number of discrete amino acid positions that correlate strongly with compartmentalization in the CSF were identified in both variable and constant regions of gp120 as well as in gp41. Correlated mutation analyses further identified that a subset of amino acid residues in these compartmentalization "hot spot" positions were strongly correlated with one another, suggesting they may play an important, definable role in the adaptation of viral variants to the CSF. Analysis of these hot spots in the context of a well-supported crystal structure of HIV-1 gp120 suggests mechanisms through which amino acid differences at the identified residues might contribute to viral compartmentalization in the CSF. CONCLUSIONS: The detailed analyses of SGA-derived full length HIV-1 env from subjects with both normal neurocognitive performance and the most common HAND diagnoses in the cART era allow us to identify novel and confirm previously described HIV-1 env genetic determinants of neuroadaptation and relate potential motifs to HIV-1 env structure and function. PMID- 25125215 TI - Vitamin D supplementation for treatment of seasonal affective symptoms in healthcare professionals: a double-blind randomised placebo-controlled trial. AB - BACKGROUND: Low serum 25-hydroxyvitamin D levels (25(OH)D) have been associated with a higher likelihood of seasonal affective disorder (SAD) and poor mental well-being, yet firm evidence for either remains lacking. Thus, vitamin D supplementation may alleviate symptoms associated with SAD. METHODS: This study was a randomized, single-centre, double-blind, placebo-controlled trial including healthcare professionals employed in psychiatric and somatic hospitals. 3345 healthcare professionals were invited to participate, 50 participants were screened, and 34 were able to complete the study. The main inclusion criterion was 8 points or more on question no. 2 of the Seasonal Pattern Assessment Questionnaire (SPAQ-SAD). During a 3-month period, the participants received a daily dose of 70 MUg vitamin D or placebo. The primary outcome was the sum of the self-reported questionnaire Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders (SIGH-SAD). The secondary outcome was World Health Organization-Five Well-Being Index (WHO-5) of the healthcare professionals during the winter period and the exploratory outcome measures were weight, waist circumference, blood pressure, absenteeism from work and 25(OH)D. RESULTS: There were no significant between-group differences in SIGH SAD sums at 12 weeks (p = 0.7 (CI: - 3.27 to 4.81)). However, there was a significant improvement of primary SIGH-SAD over time from inclusion (autumn winter) to the completion of the study (winter-spring) for all participants. The secondary and exploratory outcome measures were all insignificant between groups.The sums of the SIGH-SAD at 12 weeks were not significantly different [p = 0.701 (CI: 4.81-3.27)] between the groups. There was, however, a significant improvement in primary SIGH-SAD sums over time from inclusion (autumn-winter) to the completion of the study (winter-spring) in both groups. The secondary and explorative outcome measures were not significantly different between groups. CONCLUSIONS: There were no significant between-group differences in the primary (SIGH-SAD) and secondary (WH0-5) as well as the exploratory outcome measures (weight, waist circumference, blood pressure, absenteeism from work and 25(OH)D. Thus, the study failed to demonstrate an effect of vitamin D on SAD symptoms, but our findings may be limited by confounders. Furthermore, the study was underpowered and did not allow us to assess the ability of vitamin D to improve mood in those with low 25(OH)D. TRIAL REGISTRATION: ( http://www.clinicaltrials.gov registration number: NCT01462058). PMID- 25125216 TI - Uveitis in patients with late-stage cutaneous melanoma treated with vemurafenib. AB - IMPORTANCE: This case series highlights the risk of uveitis in patients treated with vemurafenib for unresectable or metastatic cutaneous melanoma. OBJECTIVE: To assess the occurrence and severity of uveitis as an adverse effect of vemurafenib therapy. DESIGN, SETTING, AND PATIENTS: In this observational small case series, data were collected successively from May 1, 2012, through February 31, 2013, from patients with clinical signs of ocular inflammation treated with vemurafenib at the Department of Ophthalmology, Cochin-Hotel-Dieu Hospital. MAIN OUTCOMES AND MEASURES: Patients' demographics, vemurafenib dosages, and the intervals between the onset of treatment and the first ocular symptoms were recorded. The characteristics of ocular inflammatory manifestations were analyzed. The effect of the discontinuation of vemurafenib therapy on ocular manifestations was assessed, as well as the effect of rechallenging when vemurafenib was reintroduced. RESULTS: Seven patients (mean [SD] age, 74.7 [4.0] years) had uveitis. The vemurafenib dose was 960 mg twice per day in 6 patients and a half dose in 1 patient. The mean (SD) time until the appearance of ocular signs was 5.6 (2.3) months (range, 19 days to 7 months), and inflammation ranged from mild or low-grade anterior uveitis to severe explosive panuveitis complicated by retinal detachment. Signs of ocular inflammation were always bilateral. Optical coherence tomography revealed a macular edema in only 1 of the 7 patients. Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7 patients. The rechallenge at treatment reintroduction was positive in 2 of 7 patients. CONCLUSIONS AND RELEVANCE: This small case series highlights that uveitis can be a noteworthy adverse effect of vemurafenib therapy in patients with metastatic cutaneous melanoma. However, these cases of uveitis were usually restricted to the anterior segment and manageable with local corticosteroid therapy, which justified the continuation of vemurafenib therapy because the benefits regarding the patients' survival were greater than the risk to their vision. PMID- 25125217 TI - Refractometer assessment of colostral and serum IgG and milk total solids concentrations in dairy cattle. AB - BACKGROUND: Estimation of the quantity of colostral IgG or serum IgG absorbed following ingestion of colostrum by calves is essential for monitoring the effectiveness of colostrum feeding practices on dairy farms. Milk total solids concentrations determination is a critical part of quality assessment of nonsaleable whole milk prior to feeding to calves. To date, on-farm methods to assess colostral IgG, serum IgG or milk total solids concentrations have been performed separately with various instruments. The objective of this study was to evaluate the diagnostic performance of a single electronic, hand-held refractometer for assessing colostral and serum IgG concentrations and milk total solids in dairy cattle. Colostral IgG, serum IgG and milk total solids concentrations were determined by the refractometer. Corresponding analysis of colostral and serum IgG concentrations were determined by radial immunodiffusion (RID) while milk total solids were determined by spectrophotometry. Sensitivity and specificity of the refractometer for colostrum and serum samples were calculated as determined by RID. Sensitivity and specificity of the refractometer for milk samples was calculated as determined by spectrophotometry. RESULTS: The sensitivity of the refractometer was 1 for colostral IgG, serum IgG and milk total solids determinations. Specificity of the refractometer was 0.66, 0.24 and 0 for colostral IgG, serum IgG and milk total solids determinations, respectively. The refractometer underestimated colostral IgG, serum IgG and milk total solids concentrations compared to the concentrations determined by RID or spectrophotometry. CONCLUSIONS: The refractometer was an acceptable, rapid, convenient on-farm method for determining colostral IgG and milk total solids. The refractometer was not an acceptable method for determination of serum IgG concentrations as it severely underestimated the serum IgG concentrations. PMID- 25125218 TI - Circulating microRNAs as a marker for liver injury in human immunodeficiency virus patients. AB - Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in HIV patients with regard to the extent and etiology of liver injury. Total RNA was extracted from 335 serum samples of HIV patients and 22 healthy control participants using Qiazol. Comprehensive polymerase chain reaction (PCR) array analyses (768 miRNA) were performed in serum samples of eight HIV, eight HIV/HCV (hepatitis C virus), six HCV patients, and three healthy controls. Reverse transcription (RT)-PCR measured levels of miRNA-122, miRNA-22, and miRNA-34a in serum samples of 335 patients and 19 healthy control participants. Liver injury and fibrosis in these patients were defined using aspartate aminotransferase (AST) levels, fibrosis-4 (FIB-4) index and AST-to-platelet ratio index (APRI) score. The miRNA pattern of HIV/HCV samples showed altered expression of 57 and 33 miRNA compared to HCV and HIV infection, respectively. miRNA-122, miRNA-22, and miRNA-34a were highly up-regulated in HIV/HCV patients. Analyzing the entire cohort, these miRNAs were correlated with liver function tests and were independent predictors of liver injury (AST >2 * ULN). miRNA-122 and miRNA-22 were associated with relevant fibrosis (FIB-4 >1.45; APRI >1). Circulating levels of miRNA-122 were independent predictors for relevant fibrosis in HIV patients. Interestingly, miRNA-122 and miRNA-34a levels were higher in HIV/HCV patients, miRNA-22 levels were highest in HIV/HBV patients, and circulating levels of miRNA 34a correlated positively with illicit drug use and ethanol consumption. CONCLUSION: Circulating miRNA-122, miRNA-22, and miRNA-34a correlates with the etiology of liver injury in HIV patients. These biomarkers not only mirror different mechanisms of hepatic injury, but also are independent predictors of liver injury in HIV patients. PMID- 25125220 TI - Ribonuclease A inhibition by carboxymethylsulfonyl-modified xylo- and arabinopyrimidines. AB - A group of acidic nucleosides were synthesized to develop a new class of ribonuclease A (RNase A) inhibitors. Our recent study on carboxymethylsulfonyl modified nucleosides revealed some interesting results in RNase A inhibition. This positive outcome triggered an investigation of the role played by secondary sugar hydroxy groups in inhibiting RNase A activity. Uridines and cytidines modified with ?SO2 CH2 COOH groups at the 2'- and 3'-positions show good inhibitory properties with low inhibition constant (Ki ) values in the range of 109-17 MUM. The present work resulted in a set of inhibitors that undergo more effective interactions with the RNase A active site, as visualized by docking studies. PMID- 25125221 TI - Improved psoriasis with weight loss: the role of behavioural factors. PMID- 25125219 TI - Dietary guideline adherence for gastroesophageal reflux disease. AB - BACKGROUND: Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disease, and the cost of health care and lost productivity due to GERD is extremely high. Recently described side effects of long-term acid suppression have increased the interest in nonpharmacologic methods for alleviating GERD symptoms. We aimed to examine whether GERD patients follow recommended dietary guidelines, and if adherence is associated with the severity and frequency of reflux symptoms. METHODS: We conducted a population-based cross sectional study within the Kaiser Permanente Northern California population, comparing 317 GERD patients to 182 asymptomatic population controls. All analyses adjusted for smoking and education. RESULTS: GERD patients, even those with moderate to severe symptoms or frequent symptoms, were as likely to consume tomato products and large portion meals as GERD-free controls and were even more likely to consume soft drinks and tea [odds ratio (OR) = 2.01 95% confidence interval (CI) 1.12-3.61; OR = 2.63 95% CI 1.24-5.59, respectively] and eat fried foods and high fat diet. The only reflux-triggering foods GERD patients were less likely to consume were citrus and alcohol [OR = 0.59; 95% CI: 0.35-0.97 for citrus; OR = 0.41 95% CI 0.19-0.87 for 1 + drink/day of alcohol]. The associations were similar when we excluded users of proton pump inhibitors. CONCLUSIONS: GERD patients consume many putative GERD causing foods as frequently or even more frequently than asymptomatic patients despite reporting symptoms. These findings suggest that, if dietary modification is effective in reducing GERD, substantial opportunities for nonpharmacologic interventions exist for many GERD patients. PMID- 25125222 TI - Sex steroids as pheromones in mammals: the exceptional role of estradiol. AB - This article is part of a Special Issue (Chemosignals and Reproduction). Whether from endogenous or exogenous sources, 17beta-estradiol (E2) has very powerful influences over mammalian female reproductive physiology and behavior. Given its highly lipophilic nature and low molecular mass, E2 readily enters excretions and can be absorbed from exogenous sources via nasal, cutaneous, and other modes of exposure. Indeed, systemic injection of tritiated estradiol ((3)H-E2) into a male mouse or bat has been shown to produce significant levels of radioactivity in the reproductive tissues and brain of cohabiting female conspecifics. Bioactive E2 and other steroids are naturally found in male mouse urine and other excretions, and males actively direct their urine at proximate females. Very low doses of E2 can mimic the Bruce effect (disruption of peri-implantation pregnancy by novel males), the Vandenbergh effect (early reproductive maturation induced by novel males), and male-induced estrus and ovulation. Males' capacities to induce the Bruce and Vandenbergh effects can both be diminished by manipulations that reduce their urinary E2. Uterine dynamics during the Bruce and Vandenbergh effects are consistent with the actions of E2. Collectively, these data demonstrate a critical role of male-sourced E2 in these major mammalian pheromonal effects. PMID- 25125223 TI - What is the meaning of a nonresolved viral nucleic acid test-reactive minipool? AB - BACKGROUND: This study aimed at analyzing the prevalence of hepatitis B virus (HBV) DNA among hepatitis B surface antigen (HBsAg)-negative donations by cobas TaqScreen MPX test (Roche Molecular Systems) and discussing the meaning of a reactive minipool (MP) that does not resolve to an individual donation (ID) reactive result. STUDY DESIGN AND METHODS: Nucleic acid amplification testing (NAT) was performed in 12 Chinese blood centers on 826,044 serologic negative donations in MPs of six. MP-reactive pools that were resolved to ID-reactive donations were confirmed by Roche TaqMan viral load assays. Antibody to hepatitis B surface antigen and antibody to hepatitis B core antigen (anti-HBc) results were also analyzed. Cycle threshold (Ct) values of reactive MPs were analyzed in relation to the probability of pool resolution. RESULTS: A total of 1267 of 137,674 pools were reactive, of which 839 donations were reactive by ID-NAT. The MP6 HBV NAT-yield rate lay between 1 in 1600 and 1 in 1000. At MP Ct values equal or below 37, the probability of pool resolution was approximately 80%. The prevalence of anti-HBc in ID-reactive donations was 81%. The proportion of reactive pools that could not be resolved was 36%. The prevalence of anti-HBc in donations implicated in nonresolved MPs was significantly higher than those in nonreactive MPs (48% vs. 37%, p = 0.016). CONCLUSION: The anti-HBc data suggest that approximately 10% of nonresolved MPs contain HBV DNA from a low-viral-load occult carrier. We consider ID-NAT resolution testing in duplicate to minimize HBV transmission risk associated with transfusing nonreactive donations implicated in reactive MPs. PMID- 25125224 TI - Quantification of the triglyceride fatty acid composition with 3.0 T MRI. AB - The aim of this work was to validate a sequential method for quantifying the triglyceride fatty acid composition with 3.0 T MRI. The image acquisition was performed with a 3D spoiled gradient multiple echo sequence. A specific phase correction algorithm was implemented to correct the native phase images for wrap, zero- and first-order phase and rebuild the real part images. Then, using a model of a fat (1)H MR spectrum integrating nine components, the number of double bonds (ndb) and the number of methylene-interrupted double bonds (nmidb) were derived. The chain length (CL) was obtained from these parameters using heuristic approximation. Validations were performed on different vegetable oils whose theoretical fatty acid composition was used as reference and in five human subjects. In vivo measurements were made in the liver and in the subcutaneous and visceral adipose tissues. Linear regressions showed strong correlations between ndb and nmidb quantified with MRI and the theoretical values calculated using oil composition. Mean ndb/nmidb/CL were 1.80 +/- 0.25/0.51 +/- 0.21/17.43 +/- 0.07, 2.72 +/- 0.31/0.94 +/- 0.16/17.47 +/- 0.08 and 2.53 +/- 0.21/0.84 +/- 0.14/17.43 +/- 0.07 in the liver, subcutaneous and visceral adipose tissues respectively. The results suggest that the triglyceride fatty acid composition can be assessed in human fatty liver and adipose tissues with a clinically relevant MRI method at 3.0 T. PMID- 25125227 TI - Designing technology to meet the therapeutic demands of acute renal injury in neonates and small infants. AB - Within paediatric intensive care units (PICU), clinicians face an increasing demand to support neonates and small infants with acute renal injury or medication-resistant oedema. Of all PICU admissions, fluid overload or a requirement for renal replacement therapy (RRT) is a poor prognostic factor, resulting in death in 25-50 % of such babies. For those who survive, RRT is supportive until kidney recovery, but up to 30 % of babies may have chronic kidney sequelae. Owing to their size, neonates and small infants present specific challenges for dialysis. Dialysis technology was designed for use in adults and had to be adapted for pediatric use, creating a less than ideal treatment environment fraught with complications. Consequently, wherever possible, the vast majority of physicians default to peritoneal dialysis. Clinicians now have access to two new dialysis systems with technology specifically designed for use in babies ranging from 800 g to 8 kg: the CARPEDIEM and Nidus exhibit preliminary data that demonstrates both purification and ultrafiltration capability, with safety records that exceed any existing systems presently in practice. These are truly exciting times, as these systems have the potential to revolutionise how such babies in the PICU are treated. PMID- 25125226 TI - Viral surveillance and subclinical viral infection in pediatric kidney transplantation. AB - The more potent immunosuppressive therapy that has successfully reduced the incidence of acute rejection and improved graft outcomes has also resulted in a higher incidence of viral complications. Sensitive molecular methods now allow for the detection of subclinical viral infection, which is increasingly recognized due to the adoption of routine post-transplant viral surveillance protocols. The goal of viral surveillance is the detection of subclinical viral infection that triggers an intervention; one that either prevents progression to viral disease or leads to early diagnosis of viral disease, which is associated with improved outcomes. Knowledge of the epidemiology and natural history of subclinical viral infection and viral disease, as well as patient-specific risk factors, is required to establish the optimal surveillance schedule which achieves the goal of early diagnosis. Evidence that detection of subclinical viral infection can impact viral disease is variable depending on the virus. This review will summarize the current data on the role of viral surveillance for BK virus (BKV), cytomegalovirus (CMV), and the Epstein-Barr virus (EBV) in the pediatric kidney transplant population. PMID- 25125228 TI - A 2-year-old presents following methanol ingestion with serum creatinine of 8.6 mg/dl: Questions. PMID- 25125225 TI - Higher levels of cystatin C are associated with worse cognitive function in older adults with chronic kidney disease: the chronic renal insufficiency cohort cognitive study. AB - OBJECTIVES: To determine the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD). DESIGN: Prospective observational study. SETTING: Chronic Renal Insufficiency Cohort Cognitive Study. PARTICIPANTS: Individuals with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement (N = 821; mean age 64.9, 50.6% male, 48.6% white). MEASUREMENTS: Levels of serum cystatin C were categorized into tertiles; cognitive function was assessed using six neuropsychological tests. Scores on these tests were compared across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and cognitive performance (1 standard deviation difference from the mean). RESULTS: After multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the modified Mini-Mental State Examination, Buschke Delayed Recall, Trail-Making Test Part (Trails) A and Part B, and Boston Naming (P < .05 for all). This association remained statistically significant for Buschke Delayed Recall (P = .01) and Trails A (P = .03) after additional adjustment for estimated glomerular filtration rate (eGFR). The highest tertile of cystatin C was associated with greater likelihood of poor performance on Trails A (odds ratio (OR) = 2.17, 95% confidence interval (CI) = 1.16-4.06), Trails B (OR = 1.89, 95% CI = 1.09-3.27), and Boston Naming (OR = 1.85, 95% CI = 1.07-3.19) than the lowest tertile after multivariate adjustment in logistic models. CONCLUSION: In individuals with CKD, higher serum cystatin C levels were associated with worse cognition and greater likelihood of poor cognitive performance on attention, executive function, and naming. Cystatin C is a marker of cognitive impairment and may be associated with cognition independent of eGFR. PMID- 25125229 TI - Haemodialysing babies weighing <8 kg with the Newcastle infant dialysis and ultrafiltration system (Nidus): comparison with peritoneal and conventional haemodialysis. AB - BACKGROUND: To compare the efficacy of the Newcastle infant dialysis and ultrafiltration system (Nidus) with peritoneal dialysis (PD) and conventional haemodialysis (HD) in infants weighing <8 kg. METHODS: We compared the urea, creatinine and phosphate clearances, the ultrafiltration precision, and the safety of the Nidus machine with PD in 7 piglets weighing 1-8 kg, in a planned randomised cross-over trial in babies, and in babies for whom no other therapy existed, some of whom later graduated to conventional HD. RESULTS: Two babies entered the randomised trial; 1 recovered rapidly on PD, the other remained on the Nidus as PD failed. Additionally, 9 babies were treated on the Nidus on humanitarian grounds: 3 because of failed PD, and 3 with permanent kidney failure later converted to conventional HD. We haemodialysed 10 babies weighing between 1.8 and 5.9 kg for 2,475 h during 354 Nidus sessions without any clinically important incidents, and without detectable haemolysis. Single-lumen vascular access was used with no blood priming of circuits. The urea, creatinine and phosphate clearances using the Nidus were around 1.5 to 2.0 ml/min in piglets and babies, and were consistently higher than PD clearances, which ranged from about 0.2 to 0.8 ml/min (p <= 0.0002 for each chemical). Ultrafiltration was achieved to microlitre precision by the Nidus, but varied widely with PD. Fluid removal using conventional HD was imprecise and resulted in some hypovolaemic episodes requiring correction. CONCLUSION: The Nidus can provide HD in the Pediatric Intensive Care Unit (PICU) and outpatient intermittent HD without blood priming for babies weighing <8 kg, It generates higher dialysis clearances than PD, and delivers more precise ultrafiltration control than either PD or conventional HD. PMID- 25125231 TI - Global and cyp19a1a gene specific DNA methylation in gonads of adult rare minnow Gobiocypris rarus under bisphenol A exposure. AB - As a weak estrogenic chemical, bisphenol A (BPA) has been extensively studied for reproductive toxicity and the effects on the steroidogenesis. In the present study, we aim to explore the effects of BPA on epigenetic modification in rare minnow Gobiocypris rarus. We have detected the global and cyp19a1a gene specific DNA methylation in gonads of adult G. rarus under BPA exposure. The global DNA methylation level was significantly increased in testis of the male fish exposed to BPA for 7 days, and it was significantly increased in the ovary following 35 days exposure. DNA methyltransferases (DNMTs) catalyze the transfer of a methyl moiety from S-adenosyl-l-methionine to the cytosine of a CpG dinucleotide. The alteration of the detected dnmts mRNA expression could affect the global DNA methylation levels following 15MUg/L BPA exposure. Cytochrome P450 aromatase (CYP19A1A), is responsible for the conversion of androgens into estrogens, which plays a vital role in estrogen synthesis in gonads. In the present study, the methylation level of ovarian cyp19a1a gene was significantly suppressed and stimulated by 7- and 35-day BPA exposure, respectively. There was a significant negative correlation between cyp19a1a mRNA expression and methylation levels of the four CpGs at the 5' flanking region in the ovary of adult G. rarus following BPA exposure. So we hypothesize that there are some association between the reproductive toxicity of BPA and the global DNA methylation under BPA exposure. And the alteration of cyp19a1a expression in female G. rarus by BPA might attribute to the change of its DNA methylation status. PMID- 25125232 TI - From a "perfect storm" to "smooth sailing": policymaker perspectives on implementation and sustainment of an evidence-based practice in two states. AB - Policymakers shape implementation and sustainment of evidence-based practices (EBPs), whether they are developing or responding to legislation and policies or negotiating public sector resource constraints. As part of a large mixed-method study, we conducted qualitative interviews with 24 policymakers involved in delivery of the same EBP in two U.S. states. We analyzed transcripts via open and focused coding techniques to identify the commonality, diversity, and complexity of implementation challenges; approaches to overcoming those challenges; and the importance of system-level contextual factors in ensuring successful implementation. Key findings centered on building support and leadership for EBPs; funding and contractual strategies; partnering with stakeholders; tackling challenges via proactive planning and problem solving; and the political, legal, and systemic pressures affecting EBP longevity. The policymaker perspectives offer guidance on nurturing system and organizational practice environments to achieve positive outcomes and for optimally addressing macro-level influences that bear upon the instantiation of EBPs in public sector child welfare systems. PMID- 25125233 TI - The relationship between child maltreatment and substance abuse treatment outcomes among emerging adults and adolescents. AB - Emerging adulthood is the period of greatest risk for problematic substance use. The primary aim of the current study was to examine the relationship between a broad measure of child maltreatment and several key outcomes for a large clinical sample of emerging adults (n = 858) and adolescents (n = 2,697). The secondary aim was to examine the extent to which the relationship between child maltreatment and treatment outcomes differed between emerging adults and adolescents. Multilevel latent growth curve analyses revealed emerging adults and adolescents who experienced child maltreatment reported significantly greater reductions over time on several treatment outcomes (e.g., substance use, substance-related problems, and emotional problems). Overall, analyses did not support differential relationships between child maltreatment and changes over time in these substance use disorder treatment outcomes for emerging adults and adolescents. The one exception was that although emerging adults with child maltreatment did reduce their HIV risk over time, their improvements were not as great as were the improvements in HIV risk reported by adolescents who had experienced child maltreatment. PMID- 25125234 TI - [Acute on chronic respiratory failure in interstitial pneumonias]. AB - BACKGROUND: Acute exacerbations of idiopathic interstitial pneumonias and exacerbations of pleuropulmonary disease in connective tissue diseases are associated with a high mortality. DIAGNOSTIC PROCEDURES: They have to be differentiated from respiratory failure in patients with interstitial lung disease as a result of infections, pulmonary embolism, cardiac failure and drug toxicity, because the latter can be treated causally. The extent and the invasivity of diagnostic procedures have to be adopted to the patient's situation. A rapid diagnosis is important in order to initiate therapies (antibiotics, anticoagulation, immunosuppression) in treatable causes of exacerbations. IMPORTANCE OF VENTILATION: The prognosis for patients who are under invasive mechanical ventilation in acute exacerbations of interstitial lung disease is poor. Especially in acute exacerbations of idiopathic pulmonary fibrosis (IPF), there is no general recommendation for either invasive or for noninvasive ventilation. In acute exacerbations of other subtypes of interstitial pneumonia, either idiopathic or as a pulmonary manifestation of connective tissue disease, and in all secondary exacerbations of idiopathic interstitial pneumonias which offer further treatment options, the decision about mechanical ventilation requires a differentiated assessment. LUNG TRANSPLANTATION: In younger patients with interstitial lung disease and a progressive disease, indication for lung transplantation should be made early and before an exacerbation. If patients listed for lung transplantation experience an acute exacerbation, bridging-to transplant has to be discussed with the transplant unit. In cases without further causal treatment options palliative care must be initiated. PMID- 25125235 TI - [Physiotherapy in intensive care medicine]. AB - BACKGROUND: A high amount of recently published articles and reviews have already focused on early mobilisation in intensive care medicine. However, in the clinical setting the problem of its practicability remains as each professional group in the mobility team has its own expectations concerning the interventions made by physiotherapy. Even though there are as yet no standard operation procedures (SOP), there do exist distinctive mobilisation concepts that are well implemented in certain intensive care units (http://www.fruehmobilisierung.de/Fruehmobilisierung/Algorithmen.html). AIM: Due to these facts and the urgent need for SOPs this article presents the physiotherapeutic concept for the treatment of patients in the intensive care unit which has been developed by the author: First the patients' respiratory and motor functions have to be established in order to classify the patients and allocate them to their appropriate group (one out of three) according to their capacities; additionally, the patients are analysed by checking their so-called "surrounding conditions". Following these criteria a therapy regime is developed and patients are treated accordingly. By constant monitoring and re-evaluation of the treatment in accordance with the functions of the patient a dynamic system evolves. "Keep it simple" is one of the key features of that physiotherapeutic concept. Thus, a manual for the classification and the physiotherapeutic treatment of an intensive care patient was developed. METHODS: In this article it is demonstrated how this concept can be implemented in the daily routine of an intensive care unit. Physiotherapy in intensive care medicine has proven to play an important role in the patients' early rehabilitation if the therapeutic interventions are well adjusted to the needs of the patients. A team of nursing staff, physiotherapists and medical doctors from the core facility for medical intensive care and emergency medicine at the medical university of Innsbruck developed the "Mobilisation Concept for the Multidisciplinary Treatment of the Intensive Care Patient" following the principles of the physiotherapeutic concept mentioned above and published it online on the homepage of the German network for early mobilisation (http://www.fruehmobilisierung.de/Fruehmobilisierung/Algorithmen.html) in spring 2012. The biggest challenge was to find one common language for all professional groups to define the aims of mobilisation. RESULTS: The success of the implementation becomes apparent in a well structured and coordinated procedure of early mobilisation, as all partners of the rehabilitation team apply adequate treatments. As a result the patients receive the appropriate treatment at the appropriate time which greatly supports their convalescence. PMID- 25125237 TI - Organ donation video messaging: differential appeal, emotional valence, and behavioral intention. AB - Video narratives increasingly are used to draw the public's attention to the need for more registered organ donors. We assessed the differential impact of donation messaging videos on appeal, emotional valence, and organ donation intentions in 781 non-registered adults. Participants watched six videos (four personal narratives, one informational video without personal narrative, and one unrelated to donation) with or without sound (subtitled), randomly sequenced to minimize order effects. We assessed appeal, emotional valence, readiness to register as organ donors, and donation information-seeking behavior. Compared to other video types, one featuring a pediatric transplant recipient (with or without sound) showed more favorable appeal (p < 0.001), generated more positive emotional valence (p < 0.01), and had the most favorable impact on organ donor willingness (p < 0.001). Ninety-five (12%) participants clicked through to a donation website after viewing all six videos. Minority race (OR = 1.94, 95% CI = 1.20, 3.13, p = 0.006), positive change in organ donor readiness (OR = 0.26, 95% CI = 0.14, 0.48, p < 0.001), and total positive emotion (OR = 1.05, 95% CI = 1.03, 1.07, p < 0.001) were significant multivariable predictors of clicking through to the donation website. Brief, one-min videos can have a very dramatic and positive impact on willingness to consider donation and behavioral intentions to register as an organ donor. PMID- 25125238 TI - BDNF val66met genotype and schizotypal personality traits interact to influence probabilistic association learning. AB - The brain derived neurotrophic factor (BDNF) val66met polymorphism rs6265 influences learning and may represent a risk factor for schizophrenia. Healthy people with high schizotypal personality traits display cognitive deficits that are similar to but not as severe as those observed in schizophrenia and they can be studied without confounds of antipsychotics or chronic illness. How genetic variation in BDNF may impact learning in individuals falling along the schizophrenia spectrum is unknown. We predicted that schizotypal personality traits would influence learning and that schizotypal personality-based differences in learning would vary depending on the BDNF val66met genotype. Eighty-nine healthy adults completed the Schizotypal Personality Questionnaire (SPQ) and a probabilistic association learning test. Blood samples were genotyped for the BDNF val66met polymorphism. An ANOVA was performed with BDNF genotype (val homozygotes and met-carriers) and SPQ score (high/low) as grouping variables and probabilistic association learning as the dependent variable. Participants with low SPQ scores (fewer schizotypal personality traits) showed significantly better learning than those with high SPQ scores. BDNF met-carriers displaying few schizotypal personality traits performed best, whereas BDNF met-carriers displaying high schizotypal personality traits performed worst. Thus, the BDNF val66met polymorphism appears to influence probabilistic association learning differently depending on the extent of schizotypal personality traits displayed. PMID- 25125239 TI - The role of serotonin in adult hippocampal neurogenesis. AB - Serotonin is probably best known for its role in conveying a sense of contentedness and happiness. It is one of the most unique and pharmacologically complex monoamines in both the peripheral and central nervous system (CNS). Serotonin has become in focus of interest for the treatment of depression with multiple serotonin-mimetic and modulators of adult neurogenesis used clinically. Here we will take a broad view of serotonin from development to its physiological role as a neurotransmitter and its contribution to homeostasis of the adult rodent hippocampus. This chapter reflects the most significant findings on cellular and molecular mechanisms from neuroscientists in the field over the last two decades. We illustrate the action of serotonin by highlighting basic receptor targeting studies, and how receptors impact brain function. We give an overview of recent genetically modified mouse models that differ in serotonin availability and focus on the role of the monoamine in antidepressant response. We conclude with a synthesis of the most recent data surrounding the role of serotonin in activity and hippocampal neurogenesis. This synopsis sheds light on the mechanisms and potential therapeutic model by which serotonin plays a critical role in the maintenance of mood. PMID- 25125240 TI - Spontaneous recovery from extinction in the infant rat. AB - Within the Pavlovian conditioning framework, extinction is a procedure in which, after conditioning, the conditioned stimulus (CS) is repeatedly presented without the unconditioned stimulus (US). During this procedure the conditioned response (CR) is gradually attenuated. It has been suggested that extinction during the early stages of ontogeny is a qualitatively different process from extinction in adulthood: during infancy, extinction may result in erasure of the memory, while during adulthood extinction involves new learning. This conclusion was supported by studies showing that renewal, reinstatement or spontaneous recovery procedures were not effective during infancy for recovering the CR once it had been extinguished. These studies used the freezing response as the only behavioral index, although some recent evidence indicates that the absence of freezing after conditioning or after extinction does not necessarily imply a deficit in memory, and that other behavioral indexes may be more sensitive to detecting conditioning effects. The goal of the present study was to analyze extinction in preweanling rats by examining the possibility of the spontaneous recovery of a conditioned fear response, measured through a different set of mutually-exclusive behaviors that constitute an exhaustive ethogram, and including control groups (Experiment 1: US-Only and CS-Only; Experiment 2: US-Only, CS-Only and Unpaired) in order to examine whether non-associative learning may explain quantitative or qualitative changes in the frequency of specific responses during extinction or recovery. Extinction produced changes in the expression of freezing, grooming and exploration, and the clearest evidence of spontaneous recovery came from the analysis of freezing behavior. The pattern of behavior observed during extinction is compatible with theoretical approaches which consider different dynamic behavioral systems, and it also fit in well with a molar approach to the analysis of behavior, which considers that extinction involves a transition from one allocation of time among behaviors to another allocation, rather than a loss of strength in any particular discrete response. These results have implications for the study of extinction during infancy, since they are compatible with the hypothesis that the original memory survives extinction, and highlight the importance of control conditions for detecting this effect during this ontogenetic period. PMID- 25125241 TI - Patient expectations in day surgery unit: our experience. PMID- 25125242 TI - Laser all-ceramic crown removal-a laboratory proof-of-principle study-phase 2 crown debonding time. AB - BACKGROUND AND OBJECTIVES: The removal of all-ceramic crowns is a time consuming procedure in the dental office. Little research has been done in alternative removal techniques for all-ceramic crowns. The objective of the second phase of this proof-of-principle laboratory pilot study was to evaluate whether Ivoclar Vivadent all-ceramic crowns can be efficiently removed from natural teeth without damage to the underlying tooth structure using an Erbium laser. STUDY DESIGN/MATERIALS AND METHODS: The ceramic materials used were IPS E.max CAD Lithium-disilicate (LS2 ) (E.max CAD) and IPS E.max ZirCAD Zirconium-oxide (ZrO2 ) (ZirCAD) (Ivoclar, Vivadent, Liechtenstein). Molars, either as stand-alone teeth or placed in an artificial row of teeth, were prepared to receive all ceramic crowns. Copings and full contour crowns with either featheredge or regular margins were produced. The all-ceramic crowns were bonded to the teeth with Ivoclar Multilink Automix. The time for Er:YAG laser debonding of each crown was then measured. The Er:YAG (LiteTouch, Syneron, Yokneam, Israel) was used with an 1,100 um diameter fiber tip with energies up to 600 mJ per pulse (wavelength 2,940 nm, 10 Hz repetition rate, pulse duration 100 us at 126 mJ/pulse, and 400 us at 590 mJ/pulse). The irradiation was applied at a distance of 10 mm from the crown surface following a defined pattern. Air-water spray was applied to the crowns at a rate of 67 ml/minute. RESULTS: All of the all-ceramic crowns were successfully debonded with the laser. On average, an all-ceramic E.max CAD crown was debonded in 190 +/- 92 seconds (average +/- SD). The debonding time for ZirCAD featheredge crowns was 226 +/- 105 seconds and for ZirCAD crowns with regular margins it was 312 +/- 102 seconds. No crowns fractured and no damage to the underlying dentin was detected. The bonding cement deteriorated due to the Er:YAG irradiation. Additionally, no carbonization at the dentin/cement interface was observed. CONCLUSION: Er:YAG laser energy can successfully be used to efficiently debond all-ceramic full contour crowns from natural teeth without damage to the underlying tooth structure. Lasers Surg. Med. 46:636-643, 2014. (c) 2014 Wiley Periodicals, Inc. PMID- 25125236 TI - Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like phenotypes with observed and predicted levels of mosaicism. AB - BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS. METHODS: We screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing. RESULTS: Pathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3] (28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1 [0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11 demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of undetected mosaic cases we used recursive partitioning to identify discriminating features in the NIPBL-positive subgroup. Filtering of the mutation-negative group on these features classified at least 18% as 'NIPBL-like'. A computer composition of the average face of this NIPBL-like subgroup was also more typical in appearance than that of all others in the mutation-negative group supporting the existence of undetected mosaic cases. CONCLUSIONS: Future diagnostic testing in 'mutation-negative' CdLS thus merits deeper sequencing of multiple DNA samples derived from different tissues. PMID- 25125243 TI - Abdominal ultrasound-guided transvaginal myometrial core needle biopsy for the definitive diagnosis of suspected adenomyosis in 1032 patients: a retrospective study. AB - STUDY OBJECTIVE: To assess the results of abdominal ultrasound-guided transvaginal myometrial core needle biopsy (CNB) for the definitive diagnosis of adenomyosis. DESIGN: Retrospective study (Canadian Task Force classification II 3). SETTING: Private practice. PATIENTS: A total of 1032 consecutive premenopausal women aged 22 to 53 years who had undergone myometrial CNB and uterine-preserving surgery to treat adenomyosis, which was preliminarily diagnosed on the basis of symptoms and ultrasonographic findings. INTERVENTION: Transvaginal myometrial CNB under abdominal ultrasound guidance. MEASUREMENTS AND MAIN RESULTS: The mean age of the 1032 patients was 41.4 years (range, 22-53 years); 61% were aged 40 to 49 years, and 33% were aged 30 to 39 years. The mean Pictorial Blood Loss Assessment Chart (PBAC) score was 271.1, and total pain score was 11.79. The mean anterior myometrial thickness was 2.79 cm (range, 0.7 8.7 cm), and the posterior myometrial thickness was 3.72 cm (range, 1.1-9.4 cm). A total of 2596 myometrial tissue cores were obtained from thickened myometrium via abdominal ultrasound-guided transvaginal myometrial CNB. At histopathologic examination the tissue cores demonstrated adenomyosis in 2167, myometrial hypertrophy in 343, and leiomyoma in 86. Patients were classified into a concordant group (adenomyosis only, adenomyosis plus hypertrophy, and adenomyosis plus leiomyoma; n = 951) and a discordant group (hypertrophy and leiomyoma; n = 81), depending on conformance between the pathologic result and the preliminary ultrasonographic diagnosis. The study showed a 92.26% concordance rate of adenomyosis between the transvaginal myometrial CNB and ultrasonographic diagnoses. The mean number of tissue cores in the discordant (n = 2.12) and concordant (n = 2.55) groups differed significantly (p < .05). CONCLUSION: Abdominal ultrasound-guided transvaginal myometrial CNB can be used in the definitive diagnosis of clinically and/or sonographically suspected adenomyosis in patients undergoing uterine-preserving surgery. Future research should focus on improving the definitive diagnostic rate of adenomyosis by using transvaginal myometrial CNB. PMID- 25125244 TI - Incisional negative pressure wound therapy after hemiarthroplasty for femoral neck fractures - reduction of wound complications. AB - The aim of the study was to evaluate the use of incisional negative pressure wound therapy (iNPWT) in wound healing after femoral neck fracture (FNF) treated with hip hemiarthroplasty (HA) and its influence on postoperative seromas, wound secretion, as well as time and material consumption for dressing changes. The study is a prospective randomised evaluation of iNPWT in patients with large surgical wounds after FNF. Patients were randomised either to be treated by iNPWT (group A) or a standard wound dressing (group B). Follow-up included ultrasound measurements of seroma volumes on postoperative days 5 and 10, duration of wound secretion, and time and material spent for wound dressing changes. For comparison of the means, we used the t-test for independent samples, P > 0.05 was considered significant. There were 21 patients randomised in this study. Group A (11 patients, 81.6 +/- 5.2 years of age) developed a seroma of 0.257 +/- 0.75 cm(3) after 5 days and had a secretion of 0.9 +/- 1.0 days, and the total time for dressing changes was 14.8 +/- 3.9 minutes, whereas group B (ten patients, 82.6 +/ 8.6 years of age) developed a seroma of 3.995 +/- 5.01 cm(3) after 5 days and had a secretion of 4.3 +/- 2.45 days, and the total time for dressing changes was 42.9 +/- 11.0 minutes. All mentioned differences were significant. iNPWT has been used on many different types of traumatic and non-traumatic wounds. This prospective, randomised study has demonstrated decreased development of postoperative seromas, reduction of total wound secretion days and reduction of needed time for dressing changes. PMID- 25125245 TI - Laryngoscopic characteristics in vocal leukoplakia: inter-rater reliability and correlation with histology grading. AB - OBJECTIVES/HYPOTHESIS: Vocal cord leukoplakia is a clinical diagnosis that comprises a spectrum of benignities, premalignancies, and malignancies. Accurate recordings of the visual characteristics of the affected area are important for communication between physicians and are helpful in further management. The objective of this study was to determine the laryngoscopic characteristics among patients with vocal cord leukoplakia and the reliability of examinations between different raters. STUDY DESIGN: Retrospective chart review conducted in a tertiary referral center in Taiwan. METHODS: From January 2010 to April 2013, 107 consecutive patients with vocal leukoplakia who had accepted excisional biopsy were recruited and classified into two groups according to histologic findings. The patients without clear preoperative flexible laryngoscope images stored in the picture archiving and communication system were excluded. There were 68 patients who met the inclusion criteria, and the preoperative laryngoscope images were reviewed by two laryngologists. The inter-rater reliabilities of the recordings were assessed. Correlation between the variables and histologic classification was also performed. RESULTS: The inter-rater reliability of the assessment was significant in the recordings of color, texture, size, hyperemia, thickness, and symmetry (kappa = 0.267 to 0.573, P < .05) but not in vocal cord edema. The laryngoscopic findings including color, texture, size, and hyperemia were associated with the grade of dysplasia (P < .05). CONCLUSIONS: The specific proposed laryngoscopic characteristics are consistent in the recordings between raters and can be potentially used for stratifying patients' risk. LEVEL OF EVIDENCE: 4. PMID- 25125247 TI - Guide for bougie as an adjunct for an anterior larynx. PMID- 25125248 TI - Accuracy of manual entry of drug administration data into an anesthesia information management system. AB - PURPOSE: Data on drug administration are entered manually into anesthesia information management systems (AIMS). This study examined whether these data are accurate regarding drug name, dose administered, and time of administration, and whether the stage of anesthesia influences data accuracy. METHODS: Real-time observational data on drug administration during elective operations were compared with computerized information on drug administration entered by anesthesiologists. A trained observer (K.D.) performed the observations. RESULTS: Data were collected during 57 operations which included 596 separate occasions of drug administration by 22 anesthesiologists. No AIMS records were found for 90 (15.1%) occasions of drug administration (omissions), while there were 11 (1.8%) AIMS records where drug administration was not observed. The AIMS and observer data matched for drug name on 495 of 596 (83.1%) occasions, for dose on 439 of 495 (92.5%) occasions, and for time on 476 of 495 (96.2%) occasions. Amongst the 90 omitted records, 34 (37.8%) were for vasoactive drugs with 24 (27.7%) for small doses of hypnotics. Omissions occurred mostly during maintenance: 50 of 153 (24.6%), followed by induction: 30 of 325 (9.2%) and emergence: 10 of 57 (17.5%) (P < 0.001). Time and dose inaccuracies occurred mainly during induction, followed by maintenance and emergence; time inaccuracies were 7/325 (8.3%), 10/203 (4.9%), and 0/57 (0%), respectively (P = 0.07), and dose inaccuracies were 15/325 (4.6%), 3/203 (1.5%), and 1/57 (1.7%), respectively (P = 0.11). CONCLUSION: The range of accuracy varies when anesthesiologists manually enter drug administration data into an AIMS. Charting omissions represent the largest cause of inaccuracy, principally by omissions of records for vasopressors and small doses of hypnotic drugs. Manually entered drug administration data are not without errors. Accuracy of entering drug administration data remains the responsibility of the anesthesiologist. PMID- 25125250 TI - From the Journal archives: gastric fluid volume and pH in elective patients following unrestricted oral fluid until three hours before surgery. PMID- 25125249 TI - Reversal of high spinal anesthesia with cerebrospinal lavage after inadvertent intrathecal injection of local anesthetic in an obstetric patient. AB - PURPOSE: High or total spinal anesthesia commonly results from accidental placement of an epidural catheter in the intrathecal space with subsequent injection of excessive volumes of local anesthetic. Cerebrospinal lavage has been shown to be effective at reversing the effects of high/total spinal anesthesia but is rarely considered in obstetric cases. Here, we describe the use of cerebrospinal lavage to prevent potential complications from high/total spinal anesthesia after unintentional placement of an intrathecal catheter in a labouring obstetric patient. CLINICAL FEATURES: A 34-yr-old female presented to the labour and delivery unit in active labour. Epidural anesthesia was initiated, and after the first bolus dose, the patient experienced lower extremity motor block and shortness of breath. A high spinal was confirmed, and cerebrospinal lavage was performed. In total, 40 mL of cerebrospinal fluid (CSF) were exchanged for an equal volume of normal saline. The patient's breathing difficulties and motor block resolved quickly, and a new epidural catheter was placed after removal of the spinal catheter. Pain control was effective, and the patient delivered a healthy baby. CONCLUSION: We show that exchange of CSF for normal saline can be used successfully to manage a high spinal in an obstetric patient. Our results suggest that CSF lavage could potentially be an important and helpful adjunct to the conventional supportive management of obstetric patients in the event of inadvertent high or total spinal anesthesia. PMID- 25125246 TI - Lingual traction to facilitate fibreoptic intubation in patients with difficult airways under general anesthesia. PMID- 25125251 TI - Blind nasal intubation: teaching a dying art. PMID- 25125252 TI - Providing quality in anesthesia care in low- and middle-income countries. PMID- 25125254 TI - Addressing variant pathogenicity: the TorsinA (TOR1A) gene as a model. PMID- 25125257 TI - CHK it out! Blocking WEE kinase routs TP53 mutant cancer. AB - Mutations in TP53, encoding the master tumor suppressor p53, have posed a developmental therapeutic dilemma due to inability to target loss of function. Inhibition of WEE1 or CHK1 kinase, negative regulators of the G2-M checkpoint, selectively sensitizes p53-deficient cells to exogenous DNA damage, abrogating G2 arrest and precipitating mitotic catastrophe. PMID- 25125258 TI - Design of phase I combination trials: recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee. AB - Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to maximize the pharmacodynamic effect. The development of combination regimens, while desirable, poses unique challenges. These include the selection of agents for combination therapy that may lead to improved efficacy while maintaining acceptable toxicity, the design of clinical trials that provide informative results for individual agents and combinations, and logistic and regulatory challenges. The phase I trial is often the initial step in the clinical evaluation of a combination regimen. In view of the importance of combination regimens and the challenges associated with developing them, the Clinical Trial Design (CTD) Task Force of the National Cancer Institute Investigational Drug Steering Committee developed a set of recommendations for the phase I development of a combination regimen. The first two recommendations focus on the scientific rationale and development plans for the combination regimen; subsequent recommendations encompass clinical design aspects. The CTD Task Force recommends that selection of the proposed regimens be based on a biologic or pharmacologic rationale supported by clinical and/or robust and validated preclinical evidence, and accompanied by a plan for subsequent development of the combination. The design of the phase I clinical trial should take into consideration the potential pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity. Depending on the specific hypothesized interaction, the primary endpoint may be dose optimization, pharmacokinetics, and/or pharmacodynamics (i.e., biomarker). PMID- 25125264 TI - High variability of atmospheric mercury in the summertime boundary layer through the central Arctic Ocean. AB - The biogeochemical cycles of mercury in the Arctic springtime have been intensively investigated due to mercury being rapidly removed from the atmosphere. However, the behavior of mercury in the Arctic summertime is still poorly understood. Here we report the characteristics of total gaseous mercury (TGM) concentrations through the central Arctic Ocean from July to September, 2012. The TGM concentrations varied considerably (from 0.15 ng/m(3) to 4.58 ng/m(3)), and displayed a normal distribution with an average of 1.23 +/- 0.61 ng/m(3). The highest frequency range was 1.0-1.5 ng/m(3), lower than previously reported background values in the Northern Hemisphere. Inhomogeneous distributions were observed over the Arctic Ocean due to the effect of sea ice melt and/or runoff. A lower level of TGM was found in July than in September, potentially because ocean emission was outweighed by chemical loss. PMID- 25125265 TI - Caries experience and use of dental services in rural and urban adults and older adults from central Chile. AB - OBJECTIVE: To determine whether there is a relationship between the use of dental services and caries experience in adults and older adults from central Chile. MATERIALS AND METHODS: A sample of 453 adults, 35-44 years of age, and 438 older adults, 65-74 years of age, was interviewed and examined using World Health Organisation (WHO) methods. Sociodemographic variables were also registered. Caries experience was assessed using the Decayed, Missing and Filled teeth (DMFT) index. Multiple linear regression models were used to determine whether there was an association between the independent variables and caries experience. RESULTS: Caries prevalence was 99.6% for adults [DMFT score = 14.89 (+/-6.16)] and 99.8% for older adults [DMFT score = 25.68 (+/-6.49)]. Less than half of the population - 41.7% of adults and 31.5% of older adults - received dental care. Regardless of the age group, there were no differences in the DMFT score between those who received and those who did not receive attention (P > 0.05). When the DMFT findings were analysed in greater detail, people who received dental care and urban participants had more fillings (P < 0.05) than did those who were not provided with attention or lived in rural areas, who, in turn, had more missing teeth (P < 0.05). A higher educational level was associated with a decrease of 1.15 DMFT points (P = 0.003) in the group of older adults. CONCLUSIONS: Adults and older adults from the Maule Region showed severe dental damage from caries. Although rurality and use of services do not seem to affect caries experience, they are associated with differences in fillings and missing teeth. PMID- 25125259 TI - Functional kinomics identifies candidate therapeutic targets in head and neck cancer. AB - PURPOSE: To identify novel therapeutic drug targets for p53-mutant head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: RNAi kinome viability screens were performed on HNSCC cells, including autologous pairs from primary tumor and recurrent/metastatic lesions, and in parallel on murine squamous cell carcinoma (MSCC) cells derived from tumors of inbred mice bearing germline mutations in Trp53, and p53 regulatory genes: Atm, Prkdc, and p19(Arf). Cross species analysis of cell lines stratified by p53 mutational status and metastatic phenotype was used to select 38 kinase targets. Both primary and secondary RNAi validation assays were performed on additional HNSCC cell lines to credential these kinase targets using multiple phenotypic endpoints. Kinase targets were also examined via chemical inhibition using a panel of kinase inhibitors. A preclinical study was conducted on the WEE1 kinase inhibitor, MK-1775. RESULTS: Our functional kinomics approach identified novel survival kinases in HNSCC involved in G2-M cell-cycle checkpoint, SFK, PI3K, and FAK pathways. RNAi mediated knockdown and chemical inhibition of the WEE1 kinase with a specific inhibitor, MK-1775, had a significant effect on both viability and apoptosis. Sensitivity to the MK-1775 kinase inhibitor is in part determined by p53 mutational status, and due to unscheduled mitotic entry. MK-1775 displays single agent activity and potentiates the efficacy of cisplatin in a p53-mutant HNSCC xenograft model. CONCLUSIONS: WEE1 kinase is a potential therapeutic drug target for HNSCC. This study supports the application of a functional kinomics strategy to identify novel therapeutic targets for cancer. PMID- 25125263 TI - Lower subcortical gray matter volume in both younger smokers and established smokers relative to non-smokers. AB - Although established adult smokers with long histories of nicotine dependence have lower neural tissue volume than non-smokers, it is not clear if lower regional brain volume is also observed in younger, less established smokers. The primary goal of this study was to investigate neural tissue volume in a large group of smokers and non-smokers, with a secondary goal of measuring the impact of age on these effects. We used voxel-based morphometry to compare regional gray matter volume in 118 individuals (59 smokers, 59 age- and gender-matched non smokers). Younger smokers had significantly lower gray matter volume in the left thalamus and the left amygdala than their non-smoking peers (family-wise error corrected clusters, P < 0.05). There was no correlation between smoking use variables and tissue volume among younger smokers. Established smokers had significantly lower gray matter volume than age-matched non-smokers in the insula, parahippocampal gyrus and pallidum. Medial prefrontal cortex gray matter volume was negatively correlated with pack-years of smoking among the established smokers, but not the younger smokers. These data reveal that regional tissue volume differences are not limited exclusively to established smokers. Deficits in young adults indicate that cigarette smoking may either be deleterious to the thalamus and amygdala at an earlier age than previously reported, or that pre existing differences in these areas may predispose individuals to the development of nicotine dependence. PMID- 25125266 TI - Chondroprotective effect of high-dose zoledronic acid: An experimental study in a rabbit model of osteoarthritis. AB - To address the need to impact the subchondral bone-articular cartilage interaction for the treatment of degenerative osteoarthritis (OA), bisphosphonates may be used as a means to inhibit the subchondral bone resorption. The purpose of the present study is to evaluate the chondroprotective effect of zoledronic acid (ZOL) in a model of OA. Eighteen adult male rabbits underwent an anterior cruciate ligament transection and were separated into two groups: ZOL group (n=10) received 0.6 mg/kg intravenous injection of ZOL on day 1, 15, and 29 and placebo group (n=8) received saline. The animals were euthanized at 8 weeks. Macroscopically, the ZOL group had significantly milder ulcerations, cartilage softening and fibrillation compared to the placebo group. Microscopically, morphology of the articular cartilage was better in the ZOL treated group compared with the placebo group, without complete disorganization in any section of the ZOL group. Furthermore, the chondrocytes in the ZOL treated group were mainly cloning, indicating cartilage repairing and regeneration process, while in the placebo group hypocellularity predominated. Additionally, subchondral necrosis was evident in some specimens of the placebo group. Zoledronic acid, in a high-dose regimen, proved to be chondroprotective in a well established animal model of OA. PMID- 25125267 TI - Resurgence: Response competition, stimulus control, and reinforcer control. AB - Resurgence is the relapse of a previously reinforced and then extinguished target response when extinguishing a more recently reinforced alternative response. We designed the present study to assess the contribution of stimulus-control and reinforcer-control processes in determining resurgence. In a modified resurgence procedure, we removed the alternative discriminative stimulus signaling alternative reinforcement when extinguishing the alternative response. This produced more abrupt resurgence of target responding than in a typical resurgence procedure maintaining the alternative discriminative stimulus when extinguishing the alternative response. The overall amount of resurgence did not differ. Importantly, a "renewal" control added and removed the alternative stimulus during extinction, identically as in the modified resurgence procedure. However, alternative responding was never reinforced, which produced no relapse of target responding. Therefore, the more abrupt resurgence with the modified procedure than with the typical procedure suggests removing the alternative stimulus reduced the competition between alternative and target responding. These findings revealed the importance of adding and removing alternative reinforcement in producing resurgence (reinforcer control) but little influence of simply adding and removing the alternative stimulus (stimulus control). These data suggest that clinicians should consider the long-term availability of the alternative response option when developing differential-reinforcement interventions. PMID- 25125268 TI - Chronic fistula after laparoscopic vertical gastrectomy. PMID- 25125269 TI - Homozygosity for a novel deletion downstream of the SHOX gene provides evidence for an additional long range regulatory region with a mild phenotypic effect. AB - Leri-Weill dyschondrosteosis is caused by heterozygous mutations in SHOX or its flanking sequences, including whole or partial gene deletions, point mutations within the coding sequence, and deletions of downstream regulatory elements. The same mutations when biallelic cause the more severe Langer Mesomelic dysplasia. Here, we report on a consanguineous family with a novel deletion downstream of SHOX in which homozygously deleted individuals have a phenotype intermediate between Leri-Weill dyschondrosteosis and Langer Mesomelic dysplasia while heterozygously deleted individuals are mostly asymptomatic. The deleted region is distal to all previously described 3' deletions, suggesting the presence of an additional regulatory element, deletions of which have a milder, variable phenotypic effect. PMID- 25125270 TI - Diagnostic value of S100B protein in the differential diagnosis of acute vertigo in the emergency department. AB - OBJECTIVES: Vertigo is a common presenting complaint resulting from central or peripheral etiologies. Because central causes may be life-threatening, ascertaining the nature of the vertigo is crucial in the emergency department (ED). With a broad range of potential etiologies, distinguishing central causes from benign peripheral causes is a diagnostic challenge. Cranial magnetic resonance imaging (MRI) is the recommended neuroimaging method when clinical findings are ambiguous. However, MRI scanning for every patient with an uncertain diagnosis may not be efficient or possible. Therefore, to improve ED resource utilization for patients with vertigo, there is a need to identify the subset most likely to have MRI abnormalities. It has previously been shown that S100B protein provides a useful serum marker of stroke, subarachnoid hemorrhage, and traumatic brain injury. This study evaluated whether S100B levels could predict central causes of vertigo as identified by cranial MRI in the ED. METHODS: This prospective, observational study was conducted with adult patients with acute onset vertigo (within 6 hours) in the ED of a teaching hospital in Kocaeli, Turkey. Patients with nausea or dizziness complaints without previously known vertigo or cranial pathology, and who agreed to participate in the study, were included. Patients with trauma or with neurologic findings that developed concurrent with their symptoms were excluded. Serum levels of S100B were measured with an electrochemiluminescence immunoassay kit. All subjects underwent cranial MRI. The predictors of positive MRI results were evaluated using logistic regression analysis. Sensitivity and specificity of S100B levels for identifying subjects with central causes of vertigo on MRI were calculated with receiver operating characteristic (ROC) curve. RESULTS: Of the 82 subjects included in the study, 48 (58.5%) were female, and the mean (+/-SD) age was 51 (+/-16) years. Thirty-one (37.8%) subjects had positive MRI results. Median (with interquartile range [IQR]) serum S100B levels were significantly different between MRI-negative and MRI-positive groups (median = 27.00 pg/mL, IQR = 10.00 to 44.60 vs. median = 60.94 pg/mL, IQR = 38.25 to 77.95, respectively; p = 0.04). In logistic regression analysis, subjective "he or she is spinning" (p = 0.030, odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.38 to 2.49), systolic blood pressure (sBP; p = 0.045, OR = 1.044, 95% CI = 1.021 to 1.080), and serum S100B level (p = 0.042, OR = 1.22, 95% CI = 1.018 to 1.445) were found to be independent predictors of MRI abnormalities. In the ROC analysis, S100B > 30 pg/mL predicted the clinical outcome with 83.9% sensitivity (95% CI = 66.3% to 94.5%) and 51.0% specificity (95% CI = 36.6% to 65.2%). The area under the ROC curve was 0.774 (95% CI = 0.666 to 0.881). CONCLUSIONS: To the best of our knowledge this is the first study assessing the utility of serum S100B levels for diagnosis of acute-onset vertigo. Serum S100B levels are associated with the presence of central causes of vertigo on cranial MRI. However, serum S100B levels are not sufficiently sensitive to exclude candidates from cranial MRI. PMID- 25125273 TI - Go team! PMID- 25125274 TI - Interprofessional education and collaboration: a call to action for emergency medicine. PMID- 25125271 TI - Brief intervention to increase emergency department uptake of combined rapid human immunodeficiency virus and hepatitis C screening among a drug misusing population. AB - OBJECTIVES: In this study, Increasing Viral Testing in the Emergency Department (InVITED), the authors investigated if a brief intervention about human immunodeficiency virus (HIV) and hepatitis C virus (HCV) risk-taking behaviors and drug use and misuse in addition to a self-administered risk assessment, compared to a self-administered risk assessment alone, increased uptake of combined screening for HIV and HCV, self-perception of HIV/HCV risk, and impacted beliefs and opinions on HIV/HCV screening. METHODS: InVITED was a randomized, controlled trial conducted at two urban emergency departments (EDs) from February 2011 to March 2012. ED patients who self-reported drug use within the past 3 months were invited to enroll. Drug misuse severity and need for a brief or more intensive intervention was assessed using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Participants were randomly assigned to one of two study arms: a self-administered HIV/HCV risk assessment alone (control arm) or the assessment plus a brief intervention about their drug misuse and screening for HIV/HCV (intervention arm). Beliefs on the value of combined HIV/HCV screening, self-perception of HIV/HCV risk, and opinions on HIV/HCV screening in the ED were measured in both study arms before the HIV/HCV risk assessment (pre), after the assessment in the control arm, and after the brief intervention in the intervention arm (post). Participants in both study arms were offered free combined rapid HIV/HCV screening. Uptake of screening was compared by study arm. Multivariable logistic regression models were used to evaluate factors related to uptake of screening. RESULTS: Of the 395 participants in the study, the median age was 28 years (interquartile range [IQR] = 23 to 38 years), 44.8% were female, 82.3% had ever been tested for HIV, and 67.3% had ever been tested for HCV. Uptake of combined rapid HIV/HCV screening was nearly identical by study arm (64.5% vs. 65.2%; Delta = -0.7%; 95% confidence interval [CI] = 10.1% to 8.7%). Of the 256 screened, none had reactive HIV antibody tests, but seven (2.7%) had reactive HCV antibody tests. Multivariable logistic regression analysis results indicated that uptake of screening was not related to study arm assignment, total ASSIST drug scores, need for an intervention for drug misuse, or HIV/HCV sexual risk assessment scores. However, uptake of screening was greater among participants who indicated placing a higher value on combined rapid HIV/HCV screening for themselves and all ED patients and those with higher levels of perceived HIV/HCV risk. Uptake of combined rapid HIV/HCV screening was not related to changes in beliefs regarding the value of combined HIV/HCV screening or self-perceived HIV/HCV risk (post- vs. pre-risk assessment with or without a brief intervention). Opinions regarding the ED as a venue for combined rapid HIV/HCV screening were not related to uptake of screening. CONCLUSIONS: Uptake of combined rapid HIV/HCV screening is high and considered valuable among drug using and misusing ED patients with little concern about the ED as a screening venue. The brief intervention investigated in this study does not appear to change beliefs regarding screening, self-perceived risk, or uptake of screening for HIV/HCV in this population. Initial beliefs regarding the value of screening and self-perceived risk for these infections predict uptake of screening. PMID- 25125272 TI - Emergency physicians' attitudes and preferences regarding computed tomography, radiation exposure, and imaging decision support. AB - OBJECTIVES: Although computerized decision support for imaging is often recommended for optimizing computed tomography (CT) use, no studies have evaluated emergency physicians' (EPs') preferences regarding computerized decision support in the emergency department (ED). In this needs assessment, the authors sought to determine if EPs view overutilization as a problem, if they want decision support, and if so, the kinds of support they prefer. METHODS: A 42 item, Web-based survey of EPs was developed and used to measure EPs' attitudes, preferences, and knowledge. Key contacts at local EDs sent letters describing the study to their physicians. Exploratory principal components analysis (PCA) was used to determine the underlying factor structure of multi-item scales, Cronbach's alpha was used to measure internal consistency of items on a scale, Spearman correlations were used to describe bivariate associations, and multivariable linear regression analysis was used to identify variables independently associated with physician interest in decision support. RESULTS: Of 235 surveys sent, 155 (66%) EPs responded. Five factors emerged from the PCA. EPs felt that: 1) CT overutilization is a problem in the ED (alpha = 0.75); 2) a patient's cumulative CT study count affects decisions of whether and what type of imaging study to order only some of the time (alpha = 0.75); 3) knowledge that a patient has had prior CT imaging for the same indication makes EPs less likely to order a CT (alpha = 0.42); 4) concerns about malpractice, patient satisfaction, or insistence on CTs affect CT ordering decisions (alpha = 0.62); and 5) EPs want decision support before ordering CTs (alpha = 0.85). Performance on knowledge questions was poor, with only 18% to 39% correctly responding to each of the three multiple-choice items about effective radiation doses of chest radiograph and single-pass abdominopelvic CT, as well as estimated increased risk of cancer from a 10-mSv exposure. Although EPs wanted information on patients' cumulative exposures, they feel inadequately familiar with this information to make use of it clinically. If provided with patients' cumulative radiation exposures from CT, 87% of EPs said that they would use this information to discuss imaging options with their patients. In the multiple regression model, which included all variables associated with interest in decision support at p < 0.10 in bivariate tests, items independently associated with EPs' greater interest in all types of decision support proposed included lower total knowledge scores, greater frequency that cumulative CT study count affects EP's decision to order CTs, and greater agreement that overutilization of CT is a problem and that awareness of multiple prior CTs for a given indication affects CT ordering decisions. CONCLUSIONS: Emergency physicians view overutilization of CT scans as a problem with potential for improvement in the ED and would like to have more information to discuss risks with their patients. EPs are interested in all types of imaging decision support proposed to help optimize imaging ordering in the ED and to reduce radiation to their patients. Findings reveal several opportunities that could potentially affect CT utilization. PMID- 25125275 TI - Patient safety training in pediatric emergency medicine: a national survey of program directors. AB - OBJECTIVES: The Accreditation Council for Graduate Medical Education requires training in patient safety and medical errors but does not provide specification for content or methods. Pediatric emergency medicine (EM) fellowship directors were surveyed to characterize current training of pediatric EM fellows in patient safety and to determine the need for additional training. METHODS: From June 2013 to August 2013, pediatric EM fellowship directors were surveyed via e-mail. RESULTS: Of the 71 eligible survey respondents, 57 (80.3%) completed surveys. A formal curriculum was present in 24.6% of programs, with a median of 6 hours (range = 1 to 18 hours) dedicated to the curriculum. One program evaluated the efficacy of the curriculum. Nearly 91% of respondents without formal programs identified lack of local faculty expertise or interest as the primary barrier to implementing patient safety curricula. Of programs without formal curricula, 93.6% included at least one component of patient safety training in their fellowship programs. The majority of respondents would implement a standardized patient safety curriculum for pediatric EM if one was available. CONCLUSIONS: Despite the importance of patient safety training and requirements to train pediatric EM fellows in patient safety and medical errors, there is a lack of formal curriculum and local faculty expertise. The majority of programs have introduced components of patient safety training and desire a standardized curriculum. PMID- 25125278 TI - Microanatomy of the medial collateral ligament enthesis in the bovine knee. AB - This study applied transmission and differential interference contrast light microscopy imaging methodologies to revisit the microanatomy of the ligament-bone junction of the medial collateral ligament, with the aim of providing new insights into the mechanostructural significance of the enthesis. The data show that the microscale structural features of the enthesis are more complex than the conventional description of "direct versus indirect," or "fibrous versus nonfibrous" insertions. From a materials perspective the enthesis may be viewed as a specialised functionally graded structural continuum whose unique microlevel structural adaptation contributes to maintaining both the local tissue micromechanical environment and joint function at the macrolevel. PMID- 25125279 TI - Evaluation of metals, metalloids, and ash mixture toxicity using sediment toxicity testing. AB - In December 2008, a release of 4.1 million m(3) of coal ash from the Tennessee Valley Authority Kingston Fossil Plant occurred. Ash washed into the Emory River and migrated downstream into the Clinch and Tennessee Rivers. A Baseline Ecological Risk Assessment evaluated risks to ecological receptors from ash in the river system post-dredging. This article describes the approach used and results from sediment toxicity tests, discussing any causal relationships between ash, metals, and toxicity. Literature is limited in the realm of aquatic coal combustion residue (CCR) exposures and the potential magnitude of effects on benthic invertebrates. Sediment samples along a spectrum of ash content were used in a tiered toxicity testing approach and included a combination of 10 day sediment toxicity acute tests and longer-term, partial life cycle "definitive" tests with 2 species (Hyalella azteca and Chironomus dilutus). Arsenic, and to a lesser extent Se, in the ash was the most likely toxicant causing observed effects in the laboratory toxicity tests. Sites in the Emory River with the greatest statistical and biologically significant effects had As concentrations in sediments twice the probable effects concentration of 33 mg/kg. These sites contained greater than 50% ash. Sites with less than approximately 50% ash in sediments exhibited fewer significant toxic responses relative to the reference sediment in the laboratory. The results discussed here present useful evidence of only limited effects occurring from a worst-case exposure pathway. These results provided a valuable line of evidence for the overall assessment of risks to benthic invertebrates and to other ecological receptors, and were crucial to risk management and development of project remediation goals. PMID- 25125281 TI - Young slow-progressing ALS patients are at higher risk of inappropriate and disease-quickening surgeries. PMID- 25125280 TI - Anatomical structure and ultrastructure of the endocarp cell walls of Argania spinosa (L.) Skeels (Sapotaceae). AB - The anatomical and histochemical study of young and adult endocarps of Argania spinosa (sampled from Tindouf; Algeria) shows a general structure that is similar to that of majority of stone fruits. These samples consist of tissues that contain lignified and cellulosic cell walls. The majority of the tissues are composed of sclerenchyma cells; with very thick lignified cell walls and conducting tissues. Coniferyl lignins are abundant in the majority of the lignified tissues. However, the coniferyl lignins appear at the primary xylem during lignification. Syringyl lignins are present in small quantities. The electron microscopy observation of the sclerenchyma cell walls of the young endocarp shows polylamellate strates and, cellular microfibrils in arced patterns. This architecture is observed in the cell walls of the adult endocarp only after the incubation of the tissue in methylamine. These configurations (arcs) are the result of a regular and complete rotation with a 180 degrees variation in the microfibril angle; the complete and symmetrical arcs show a helicoidal mode of construction. The observation of the sclerenchyma cells revealed the capacity of helicoidal morphogenesis to adjust itself under the influence of topological constraints, such as the presence of a large number of pit canals, which maintain symplastic transport. PMID- 25125282 TI - Biogeography and speciation of terrestrial fauna in the south-western Australian biodiversity hotspot. AB - The south-western land division of Western Australia (SWWA), bordering the temperate Southern and Indian Oceans, is the only global biodiversity hotspot recognised in Australia. Renowned for its extraordinary diversity of endemic plants, and for some of the largest and most botanically significant temperate heathlands and woodlands on Earth, SWWA has long fascinated biogeographers. Its flat, highly weathered topography and the apparent absence of major geographic factors usually implicated in biotic diversification have challenged attempts to explain patterns of biogeography and mechanisms of speciation in the region. Botanical studies have always been central to understanding the biodiversity values of SWWA, although surprisingly few quantitative botanical analyses have allowed for an understanding of historical biogeographic processes in both space and time. Faunistic studies, by contrast, have played little or no role in defining hotspot concepts, despite several decades of accumulating quantitative research on the phylogeny and phylogeography of multiple lineages. In this review we critically analyse datasets with explicit supporting phylogenetic data and estimates of the time since divergence for all available elements of the terrestrial fauna, and compare these datasets to those available for plants. In situ speciation has played more of a role in shaping the south-western Australian fauna than has long been supposed, and has occurred in numerous endemic lineages of freshwater fish, frogs, reptiles, snails and less-vagile arthropods. By contrast, relatively low levels of endemism are found in birds, mammals and highly dispersive insects, and in situ speciation has played a negligible role in generating local endemism in birds and mammals. Quantitative studies provide evidence for at least four mechanisms driving patterns of endemism in south western Australian animals, including: (i) relictualism of ancient Gondwanan or Pangaean taxa in the High Rainfall Province; (ii) vicariant isolation of lineages west of the Nullarbor divide; (iii) in situ speciation; and (iv) recent population subdivision. From dated quantitative studies we derive four testable models of historical biogeography for animal taxa in SWWA, each explicit in providing a spatial, temporal and topological perspective on patterns of speciation or divergence. For each model we also propose candidate lineages that may be worthy of further study, given what we know of their taxonomy, distributions or relationships. These models formalise four of the strongest patterns seen in many animal taxa from SWWA, although other models are clearly required to explain particular, idiosyncratic patterns. Generating numerous new datasets for suites of co-occurring lineages in SWWA will help refine our understanding of the historical biogeography of the region, highlight gaps in our knowledge, and allow us to derive general postulates from quantitative (rather than qualitative) results. For animals, this process has now begun in earnest, as has the process of taxonomically documenting many of the more diverse invertebrate lineages. The latter remains central to any attempt to appreciate holistically biogeographic patterns and processes in SWWA, and molecular phylogenetic studies should - where possible - also lead to tangible taxonomic outcomes. PMID- 25125283 TI - Trisphosphine-chelate-substituted molybdenum and tungsten nitrosyl hydrides as highly active catalysts for olefin hydrogenations. AB - Reaction of [M(NO)Cl3 (NCMe)2 ] (M=Mo, W) with (iPr2 PCH2 CH2 )2 PPh (etp(i) p) at room temperature afforded the syn/anti-[M(NO)Cl3 (mer-etp(i) p)] complexes (M=Mo, a; W, b; 3 a,b(syn,anti); syn and anti refer to the relative position of Ph(etp(i) p) and NO). Reduction of 3 a,b(syn,anti) produced [M(NO)Cl2 (mer-etp(i) p)] (4 a,b(syn)), [M(NO)Cl(NCMe)(mer-etp(i) p)] (5 a,b(syn,anti)), and [M(NO)Cl(eta(2) -ethylene)(mer-etp(i) p)] (6 a,b(syn,anti)) complexes. The hydrides [M(NO)H(eta(2) -ethylene)(mer-etp(i) p)] (7 a,b(syn,anti)) were obtained from 6 a,b(syn,anti) using NaHBEt3 (75 degrees C, THF) or LiBH4 (80 degrees C, Et3 N), respectively. 7 a,b(syn,anti) were probed in olefin hydrogenations in the absence or presence of a hydrosilane/B(C6 F5 )3 mixture. The 7 a,b(syn,anti)/Et3 SiH/B(C6 F5 )3 co-catalytic systems were highly active in various olefin hydrogenations (60 bar H2 , 140 degrees C), with maximum TOFs of 5250 h(-1) (7 a(syn,anti)) and 8200 h(-1) (7 b(syn,anti)) for 1-hexene hydrogenation. The Et3 SiH/(B(C6 F5 )3 co-catalyst is anticipated to generate a [Et3 Si](+) cation attaching to the ONO atom. This facilitates NO bending and accelerates catalysis by providing a vacant site. Inverse DKIE effects were observed for the 7 a(syn,anti)/Et3 SiH/(B(C6 F5 )3 (kH /kD =0.55) and the 7 b(syn,anti)/Et3 SiH/(B(C6 F5 )3 (kH /kD =0.65) co-catalytic mixtures (20 bar H2 /D2 , 140 degrees C). PMID- 25125284 TI - Postnatal depression. PMID- 25125285 TI - ALien Biotic IndEX (ALEX) - a new index for assessing impacts of alien species on benthic communities. AB - Biotic indices are mainly aimed at assessing levels of deterioration caused by chemical or organic pollution. However, no biotic index to date has been developed to detect impacts of alien species on benthic communities. In this paper, a new biotic index, namely ALEX, is proposed to address the objectives of the Water Framework Directive and was tested in Mersin Bay (Levantine Sea, Turkey). Species were divided into four biogeographic groups, namely native species, casual species, established species and invasive species, and the metric considers the relative importance of these groups in samples. The index classified the ecological status of some stations which are shallow, and close to harbor and river mouths as bad or poor in February and October. The ALEX values were positively and significantly correlated with total nitrogen, silicate and silt percentage in sediment, and negatively correlated with depth and the distance from the harbor. PMID- 25125286 TI - Simulation of the potential effects of CO2 leakage from carbon capture and storage activities on the mobilization and speciation of metals. AB - One of the main risks associated with carbon capture and storage (CCS) activities is the leakage of the stored CO2, which can result in several effects on the ecosystem. Laboratory-scale experiments were performed to provide data on the possible effects of CO2 leakage from CCS on the mobility of metals previously trapped in sediments. Metal-contaminated sediments were collected and submitted to acidification by means of CO2 injection using different pH treatments. The test lasted 10 days, and samples were collected at the beginning and at the end of the experiment for metal analysis. The results revealed increases in the mobility of metals such as Co, Cu, Fe, Pb and Zn due to pH decreases. Geochemical modeling demonstrated that acidification influenced the speciation of the metals, increasing the concentrations of their free forms. These data suggest the possible sediment contamination consequences of accidental CO2 leakage during CCS activities. PMID- 25125287 TI - Marine litter ensemble transport simulations in the southern North Sea. AB - The drift of marine litter in the southern North Sea was simulated with the offline Lagrangian transport model PELETS-2D. Assuming different source regions, passive tracer particles were released every 28 h within a nine-year period. Based on pre-calculated hourly wind and ocean current data, drift simulations were carried out forward and backward in time with and without the assumption of extra wind forces influencing particle movement. Due to strong variability of currents, backward simulations did not allow for the identification of particular source regions influencing given monitoring sites. Neither accumulation regions at open sea could be identified by forward simulations. A seasonal signal, however, could be identified in the number of tracer particles that reached the coastal areas. Both particle drift velocity and variability of drift paths further increased when an extra wind drift was assumed. PMID- 25125288 TI - Rapid, repeated, low-dose challenges with SIVmac239 infect animals in a condensed challenge window. AB - BACKGROUND: Simian immunodeficiency virus (SIV) infection of nonhuman primates is the predominant model for preclinical evaluation of human immunodeficiency virus (HIV) vaccines. These studies frequently utilize high-doses of SIV that ensure infection after a single challenge but do not recapitulate critical facets of sexual HIV transmission. Investigators are increasingly using low-dose challenges in which animals are challenged once every week or every two weeks in order to better replicate sexual HIV transmission. Using this protocol, some animals require over ten challenges before SIV infection is detectable, potentially inducing localized immunity. Moreover, the lack of certainty over which challenge will lead to productive infection prevents tissue sampling immediately surrounding the time of infection. FINDINGS: Here we challenged Mauritian cynomolgus macaques with 100 50% tissue culture infectious doses (TCID50) of SIVmac239 intrarectally three times a day for three consecutive days. Ten of twelve animals had positive plasma viral loads after this challenge regimen. CONCLUSIONS: This approach represents a straightforward advance in SIV challenge protocols that may avoid induction of local immunity, avoid inconsistent timing between last immunization and infection, and allow sampling immediately after infection using low-dose challenge protocols. PMID- 25125289 TI - Local vasotocin modulation of the pacemaker nucleus resembles distinct electric behaviors in two species of weakly electric fish. AB - The neural bases of social behavior diversity in vertebrates have evolved in close association with hypothalamic neuropeptides. In particular, arginine vasotocin (AVT) is a key integrator underlying differences in behavior across vertebrate taxa. Behavioral displays in weakly electric fish are channeled through specific patterns in their electric organ discharges (EODs), whose rate is ultimately controlled by a medullary pacemaker nucleus (PN). We first explored interspecific differences in the role of AVT as modulator of electric behavior in terms of EOD rate between the solitary Gymnotus omarorum and the gregarious Brachyhypopomus gauderio. In both species, AVT IP injection (10MUg/gbw) caused a progressive increase of EOD rate of about 30%, which was persistent in B. gauderio, and attenuated after 30min in G. omarorum. Secondly, we demonstrated by in vitro electrophysiological experiments that these behavioral differences can be accounted by dissimilar effects of AVT upon the PN in itself. AVT administration (1MUM) to the perfusion bath of brainstem slices containing the PN produced a small and transient increase of PN activity rate in G. omarorum vs the larger and persistent increase previously reported in B. gauderio. We also identified AVT neurons, for the first time in electric fish, using immunohistochemistry techniques and confirmed the presence of hindbrain AVT projections close to the PN that might constitute the anatomical substrate for AVT influences on PN activity. Taken together, our data reinforce the view of the PN as an extremely plastic medullary central pattern generator that not only responds to higher influences to adapt its function to diverse contexts, but also is able to intrinsically shape its response to neuropeptide actions, thus adding a hindbrain target level to the complexity of the global integration of central neuromodulation of electric behavior. PMID- 25125291 TI - Blood volume measurement by hemodilution: association with valve disease and re evaluation of the Allen Formula. AB - BACKGROUND: Total blood volume (TBV) assessment is central to the management of cardiac surgical patients with cardiopulmonary bypass (CPB). The widely accepted Allen Formula lacks accuracy in estimating TBV in these patients. Moreover, the impact of commonly encountered cardiac disease states on TBV has not been systematically investigated. The aim of this study was to determine TBV by hemodilution (TBVHD) for patients with valve disease, compare TBVHD to algorithms frequently used during cardiac surgery and to modify the Allen Formula to better fit today's patient population. METHODS: TBVHD was prospectively measured upon initiation of CPB. Ninety-six patients were grouped into 4 cohorts by preoperative diagnosis and compared to Allen and weight-based formulae in a univariate analysis: mitral regurgitation (MR), coronary artery disease requiring bypass surgery (CABG) and aortic stenosis (AS) +/- CABG. The independent effects of height and weight on TBV were correlated to the original Allen Formula by multiple linear regression. RESULTS: Patients with MR had significantly larger TBVHD compared to patients with AS, CABG or both. The smallest TBVHD was found in the patients with AS and CABG. The modified Allen Formula had an excellent model fit (R(2) = 0.88 and R(2) = 0.95 for males and females, respectively; p<0.001) while the classic formula overestimated TBV by 30% in males and females. For males, height impacted TBV calculations the most whereas weight was the predominant determinant in females. CONCLUSION: Blood volume assessment via the Allen Formula or bodyweight overestimated TBV in cardiac surgical patients, with potential implications on their management. The assumption that MR frequently presents with increased intravascular volume was confirmed whereas AS patients with coronary disease had a relatively smaller TBV. Lastly, a modified Allen Formula to better reflect today's patient population was derived to reproducibly improve accuracy in mathematical estimates of TBV. PMID- 25125292 TI - Anatomic assessment of sympathetic peri-arterial renal nerves in man. AB - BACKGROUND: Although renal sympathetic denervation therapy has shown promising results in patients with resistant hypertension, the human anatomy of peri arterial renal nerves is poorly understood. OBJECTIVES: The aim of our study was to investigate the anatomic distribution of peri-arterial sympathetic nerves around human renal arteries. METHODS: Bilateral renal arteries were collected from human autopsy subjects, and peri-arterial renal nerve anatomy was examined by using morphometric software. The ratio of afferent to efferent nerve fibers was investigated by dual immunofluorescence staining using antibodies targeted for anti-tyrosine hydroxylase and anti-calcitonin gene-related peptide. RESULTS: A total of 10,329 nerves were identified from 20 (12 hypertensive and 8 nonhypertensive) patients. The mean individual number of nerves in the proximal and middle segments was similar (39.6 +/- 16.7 per section and 39.9 +/- 1 3.9 per section), whereas the distal segment showed fewer nerves (33.6 +/- 13.1 per section) (p = 0.01). Mean subject-specific nerve distance to arterial lumen was greatest in proximal segments (3.40 +/- 0.78 mm), followed by middle segments (3.10 +/- 0.69 mm), and least in distal segments (2.60 +/- 0.77 mm) (p < 0.001). The mean number of nerves in the ventral region (11.0 +/- 3.5 per section) was greater compared with the dorsal region (6.2 +/- 3.0 per section) (p < 0.001). Efferent nerve fibers were predominant (tyrosine hydroxylase/calcitonin gene related peptide ratio 25.1 +/- 33.4; p < 0.0001). Nerve anatomy in hypertensive patients was not considerably different compared with nonhypertensive patients. CONCLUSIONS: The density of peri-arterial renal sympathetic nerve fibers is lower in distal segments and dorsal locations. There is a clear predominance of efferent nerve fibers, with decreasing prevalence of afferent nerves from proximal to distal peri-arterial and renal parenchyma. Understanding these anatomic patterns is important for refinement of renal denervation procedures. PMID- 25125290 TI - Efficient and cost effective production of active-form human PKB using silkworm larvae. AB - Protein kinase B (PKB) also known as Akt is involved in many signal transduction pathways. As alterations of the PKB pathway are found in a number of human malignancies, PKB is considered an important drug target for cancer therapy. However, production of sufficient amounts of active PKB for biochemical and structural studies is very costly because of the necessity of using a higher organism expression system to obtain phosphorylated PKB. Here, we report efficient production of active PKBalpha using the BmNPV bacmid expression system with silkworm larvae. Following direct injection of bacmid DNA, recombinant PKBalpha protein was highly expressed in the fat bodies of larvae, and could be purified using a GST-tag and then cleaved. A final yield of approximately 1 mg PKBalpha/20 larvae was recorded. Kinase assays showed that the recombinant PKBalpha possessed high phosphorylation activity. We further confirmed phosphorylation on the activation loop by mass spectrometric analysis. Our results indicate that the silkworm expression system is of value for preparation of active-form PKBalpha with phosphorylation on the activation loop. This efficient production of the active protein will facilitate further biochemical and structural studies and stimulate subsequent drug development. PMID- 25125293 TI - Catheter-based renal denervation is no simple matter: lessons to be learned from our anatomy? PMID- 25125294 TI - Paroxysmal AF catheter ablation with a contact force sensing catheter: results of the prospective, multicenter SMART-AF trial. AB - BACKGROUND: Catheter ablation is important for treatment of paroxysmal atrial fibrillation (PAF). Limited animal and human studies suggest a correlation between electrode-tissue contact and radiofrequency lesion generation. OBJECTIVES: The study sought to assess the safety and effectiveness of an irrigated, contact force (CF)-sensing catheter in the treatment of drug refractory symptomatic PAF. METHODS: A prospective, multicenter, nonrandomized study was conducted. Enrollment criteria included: >=3 symptomatic episodes of PAF within 6 months of enrollment and failure of >=1 antiarrhythmic drug (Class I to IV). Ablation included pulmonary vein isolation with confirmed entrance block as procedural endpoint. RESULTS: A total of 172 patients were enrolled at 21 sites, where 161 patients had a study catheter inserted and 160 patients underwent radiofrequency application. Procedural-related serious adverse events occurring within 7 days of the procedure included tamponade (n = 4), pericarditis (n = 3), heart block (n = 1, prior to radiofrequency application), and vascular access complications (n = 4). By Kaplan-Meier analyses, 12-month freedom from atrial fibrillation/atrial flutter/atrial tachycardia recurrence was 72.5%. The average CF per procedure was 17.9 +/- 9.4 g. When the CF employed was between investigator selected working ranges >=80% of the time during therapy, outcomes were 4.25 times more likely to be successful (p = 0.0054; 95% confidence interval: 1.53 to 11.79). CONCLUSIONS: The SMART-AF trial demonstrated that this irrigated CF-sensing catheter is safe and effective for the treatment of drug refractory symptomatic PAF, with no unanticipated device-related adverse events. The increased percent of time within investigator-targeted CF ranges correlates with increased freedom from arrhythmia recurrence. Stable CF during radiofrequency application increases the likelihood of 12-month success. (THERMOCOOL(r) SMARTTOUCH(r) Catheter for Treatment of Symptomatic Paroxysmal Atrial Fibrillation; NCT01385202). PMID- 25125295 TI - When it comes to radiofrequency catheter ablation of atrial fibrillation, have all of our wishes been granted? A perspective on the SMART-AF trial. PMID- 25125297 TI - Outcomes with digoxin in atrial fibrillation: more data, no answers. PMID- 25125296 TI - Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study. AB - BACKGROUND: Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF). OBJECTIVES: The goal of this study was to evaluate the association of digoxin with mortality in AF. METHODS: Using complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual confounding was assessed by sensitivity analysis. RESULTS: Of 122,465 patients with 353,168 person-years of follow-up (age 72.1 +/- 10.3 years, 98.4% male), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin. CONCLUSIONS: Digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF. PMID- 25125298 TI - Prevalence and characteristics of TCFA and degree of coronary artery stenosis: an OCT, IVUS, and angiographic study. AB - BACKGROUND: The relationship between features of vulnerable plaque and angiographic coronary stenosis is unknown. OBJECTIVES: The purpose of this study was to systematically investigate the absolute number, relative prevalence, and characteristics of thin-cap fibroatheroma (TCFA) at different degrees of stenosis using optical coherence tomography (OCT), intravascular ultrasound, and coronary angiography. METHODS: We identified 643 plaques from 255 subjects who underwent OCT imaging in all 3 coronary arteries. They were divided into 3 groups on the basis of angiographic diameter stenosis: Group A (30% to 49%, n = 325), Group B (50% to 69%, n = 227), and Group C (>70%, n = 91). RESULTS: OCT showed that the absolute number of TCFA was greatest in Group A (n = 58), followed by Groups B (n = 40) and C (n = 33). However, the relative prevalence of TCFA was higher in Group C (36%) than in Groups A (18%) or B (18%) (p = 0.003 and p = 0.002, respectively). Fibrous cap of TCFA was thinner in Group C than in Groups A (p < 0.001) or B (p = 0.001). intravascular ultrasound showed that the plaque burden of TCFA was largest in Group C (80.1 +/- 7.4%), compared with Groups B (67.5 +/- 9.4%) and A (58.1 +/- 8.4%). TCFA in Group C had a higher remodeling index than those in Group A (p = 0.002). CONCLUSIONS: The absolute number of TCFA is 3 times greater in nonsevere stenosis than in severe stenosis. It is, however, twice as likely for a lesion to be TCFA in cases of severe stenosis than in nonsevere stenosis. Moreover, TCFA in severely-stenotic areas had more features of plaque vulnerability. PMID- 25125299 TI - Putting TCFA in clinical perspective. PMID- 25125301 TI - The Fermi paradox and coronary artery disease. PMID- 25125300 TI - High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial. AB - BACKGROUND: It is not known whether high-risk plaque, as detected by coronary computed tomography angiography (CTA), permits improved early diagnosis of acute coronary syndromes (ACS) independently to the presence of significant coronary artery disease (CAD) in patients with acute chest pain. OBJECTIVES: The primary aim of this study was to determine whether high-risk plaque features, as detected by CTA in the emergency department (ED), may improve diagnostic certainty of ACS independently and incrementally to the presence of significant CAD and clinical risk assessment in patients with acute chest pain but without objective evidence of myocardial ischemia or myocardial infarction (MI). METHODS: We included patients randomized to the coronary CTA arm of the ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II) trial. Readers assessed coronary CTA qualitatively for the presence of nonobstructive CAD (1% to 49% stenosis), significant CAD (>=50% or >=70% stenosis), and the presence of at least 1 of the high-risk plaque features (positive remodeling, low <30 Hounsfield units plaque, napkin-ring sign, spotty calcium). In logistic regression analysis, we determined the association of high-risk plaque with ACS (MI or unstable angina pectoris) during the index hospitalization and whether this was independent of significant CAD and clinical risk assessment. RESULTS: Overall, 37 of 472 patients who underwent coronary CTA with diagnostic image quality (mean age 53.9 +/- 8.0 years; 52.8% men) had ACS (7.8%; MI n = 5; unstable angina pectoris n = 32). CAD was present in 262 patients (55.5%; nonobstructive CAD in 217 patients [46.0%] and significant CAD with >=50% stenosis in 45 patients [9.5%]). High-risk plaques were more frequent in patients with ACS and remained a significant predictor of ACS (odds ratio [OR]: 8.9; 95% CI: 1.8 to 43.3; p = 0.006) after adjustment for >=50% stenosis (OR: 38.6; 95% CI: 14.2 to 104.7; p < 0.001) and clinical risk assessment (age, sex, number of cardiovascular risk factors). Similar results were observed after adjustment for >=70% stenosis. CONCLUSIONS: In patients presenting to the ED with acute chest pain but negative initial electrocardiogram and troponin, presence of high-risk plaques on coronary CTA increased the likelihood of ACS independent of significant CAD and clinical risk assessment (age, sex, and number of cardiovascular risk factors). (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239). PMID- 25125303 TI - Glycogen synthase kinase-3 and the heart. PMID- 25125302 TI - Cardiomyocyte-specific deletion of Gsk3alpha mitigates post-myocardial infarction remodeling, contractile dysfunction, and heart failure. AB - BACKGROUND: Injury due to myocardial infarction (MI) is largely irreversible. Once an infarct has occurred, the clinical goal becomes limiting remodeling, preserving left ventricular function, and preventing heart failure. Although traditional approaches (e.g., beta-blockers) partially preserve left ventricular function, novel strategies are needed to limit ventricular remodeling post-MI. OBJECTIVES: The aim of this study was to determine the role of glycogen synthase kinase-3alpha (GSK-3alpha) in post-MI remodeling. METHODS: Mice with cardiomyocyte-specific conditional deletion of Gsk3alpha and littermate controls underwent sham or MI surgery. Heart function was assessed using serial M-mode echocardiography. RESULTS: Gsk3alpha deletion in the heart markedly limits remodeling and preserves left ventricular function post-MI. This is due at least in part to dramatic thinning and expansion of the scar in the control hearts, which was less in the heart of knockout (KO) mice. In contrast, the border zone in the KO mice demonstrated a much thicker scar, and there were more viable cardiomyocytes within the scar/border zone. This was associated with less apoptosis and more proliferation of cardiomyocytes in the KO mice. Mechanistically, reduced apoptosis was due, at least in part, to a marked decrease in the Bax/Bcl-2 ratio, and increased cardiomyocyte proliferation was mediated through cyclin E1 and E2F-1 in the hearts of the KO mice. CONCLUSIONS: Taken together, these findings show that reducing GSK-3alpha expression in cardiomyocytes limits ventricular remodeling and preserves cardiac function post MI. Specifically targeting GSK-3alpha could be a novel strategy to limit adverse remodeling and heart failure. PMID- 25125305 TI - Carotid artery stenting. AB - Carotid artery stenting (CAS) has achieved clinical equipoise with carotid endarterectomy (CEA), as evidenced by 2 large U.S. randomized clinical trials, multiple pivotal registry trials, and 2 multispecialty guideline documents endorsed by 14 professional societies. The largest randomized trial conducted in patients at average surgical risk of CEA, CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) found no difference between CAS and CEA for the combined endpoint of stroke, death, and myocardial infarction (MI) after 4 years of follow-up. The largest randomized trial comparing CAS and CEA in patients at increased surgical risk, SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy), looked at 1-year stroke, death, and MI incidence and found no difference in symptomatic patients, but a significantly better outcome in asymptomatic patients for CAS (9.9% vs. 21.5%; p = 0.02). Given that >70% of carotid revascularization procedures are performed in asymptomatic patients for primary prevention of stroke, it is incumbent upon clinicians to demonstrate that revascularization has an incremental benefit over highly effective modern medical therapy alone. PMID- 25125304 TI - Rhythm control in heart failure patients with atrial fibrillation: contemporary challenges including the role of ablation. AB - Because nonpharmacological interventions likely alter the risks and benefits associated with rhythm control, this paper reviews the role of current rhythm control strategies in atrial fibrillation. This report also focuses on the specific limitations of pharmacological interventions and the utility of percutaneous ablation in this growing population of patients with concomitant atrial fibrillation and heart failure. PMID- 25125306 TI - Revolutionizing cardiology and health care: a shared purpose makes all the difference. PMID- 25125307 TI - Pregnancy in fellowship: building a career and family. PMID- 25125308 TI - Urinary hyaluronic acid as an early predictor of acute kidney injury after cardiac surgery. PMID- 25125309 TI - Would a modified Lewis index be more specific, without marked reduction of sensitivity, in ECG diagnosis of RVH? PMID- 25125310 TI - Reply: would a modified Lewis index be more specific, without marked reduction of sensitivity, in ECG diagnosis of RVH? PMID- 25125311 TI - A commentary on the SPARC study. PMID- 25125312 TI - Coronary CT angiography again results in better patient outcomes. PMID- 25125313 TI - Reply: a commentary on the SPARC study. PMID- 25125314 TI - Recovery of left ventricular mechanics after transcatheter aortic valve implantation: effects of baseline ventricular function and postprocedural aortic regurgitation. AB - BACKGROUND: Impaired left ventricular (LV) myocardial deformation is associated with adverse outcome in patients with severe aortic stenosis (AS). The aim of this retrospective study was to assess the impact of transcatheter aortic valve implantation (TAVI) on the recovery of myocardial mechanics and the influence of postprocedural aortic regurgitation (AR). METHODS: Speckle-tracking echocardiography was used to assess multidirectional myocardial deformation (longitudinal and circumferential strain) and rotational mechanics (apical rotation and twist) before and at midterm follow-up after TAVI. Predictors of myocardial recovery, defined as a >=20% relative increase in the magnitude of global longitudinal strain compared with baseline, were examined. RESULTS: Sixty four patients (median age, 83 years; interquartile range, 77-86 years) with severe AS and high surgical risk (mean European System for Cardiac Operative Risk Evaluation score, 20 +/- 13%) were evaluated. Overall, LV longitudinal deformation was impaired at baseline compared with controls. At 5 +/- 3 months after TAVI, LV longitudinal deformation had significantly improved only in the group of patients with baseline LV ejection fractions (LVEF) <= 55%: global longitudinal strain from -9.7 +/- 3.7% to -11.8 +/- 3.2% (P = .05), longitudinal strain rate from -0.44 +/- 0.14 sec(-1) to -0.57 +/- 0.16 sec(-1) (P = .001), and early diastolic strain rate from 0.38 +/- 0.17 sec(-1) to 0.49 +/- 0.18 sec(-1) (P = .01). In patients with normal LVEFs, LV twist was supraphysiologic at baseline and normalized after TAVI (from 16.1 +/- 6.9 degrees to 11.9 +/- 6.2 degrees , P = .004). In patients with baseline LVEFs <= 55%, circumferential deformation was impaired before TAVI and improved after TAVI. Baseline LVEF (odds ratio, 0.56 per 10% increment; P = .02) and global longitudinal strain (odds ratio, 0.65 per absolute 1% increment; P < .001) were significant predictors of myocardial recovery. LV mass, volumes, and longitudinal strain failed to favorably remodel in patients with post-TAVI important AR (defined as new mild post-TAVI AR or moderate or severe post-TAVI AR [either preexisting or new AR]). CONCLUSIONS: TAVI restores LV function toward more physiologic myocardial mechanics in both normal- and depressed-LVEF groups. Patients with lower systolic function derive the most benefit in terms of longitudinal reverse remodeling. Postprocedural AR adversely affects LV structural and functional remodeling. PMID- 25125315 TI - The human meniscus: a review of anatomy, function, injury, and advances in treatment. AB - Meniscal injuries are recognized as a cause of significant musculoskeletal morbidity. The menisci are vital for the normal function and long-term health of the knee joint. The purpose of this review is to provide current knowledge regarding the anatomy and biomechanical functions of the menisci, incidence, injury patterns and the advancements in treatment options of meniscal injury. A literature search was performed by a review of PubMed, Google Scholar, MEDLINE, and OVID for all relevant articles published between 1897 and 2014. This study highlights the anatomical and biomechanical characteristics of the menisci, which may be relevant to injury patterns and treatment options. An understanding of the normal anatomy and biomechanical functions of the knee menisci is a necessary prerequisite to understanding pathologies associated with the knee. PMID- 25125316 TI - Endophthalmitis prophylaxis for cataract surgery: are intracameral antibiotics necessary? PMID- 25125317 TI - Interventions to reduce haemorrhage during myomectomy for fibroids. AB - BACKGROUND: Benign smooth muscle tumours of the uterus, known as fibroids or myomas, are often symptomless. However, about one-third of women with fibroids will present with symptoms that are severe enough to warrant treatment. The standard treatment of symptomatic fibroids is hysterectomy (that is surgical removal of the uterus) for women who have completed childbearing, and myomectomy for women who desire future childbearing or simply want to preserve their uterus. Myomectomy, the surgical removal of myomas, can be associated with life threatening bleeding. Excessive bleeding can necessitate emergency blood transfusion. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. This is an update of the review published in The Cochrane Library (2011, Issue 11). OBJECTIVES: To assess the effectiveness, safety, tolerability and costs of interventions to reduce blood loss during myomectomy. SEARCH METHODS: In June 2014, we conducted electronic searches in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO, and trial registers for ongoing and registered trials. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) that compared potential interventions to reduce blood loss during myomectomy to placebo or no treatment. DATA COLLECTION AND ANALYSIS: The two authors independently selected RCTs for inclusion, assessed the risk of bias and extracted data from the included RCTs. The primary review outcomes were blood loss and need for blood transfusion. We expressed study results as mean differences (MD) for continuous data and odds ratios for dichotomous data, with 95% confidence intervals (CI). We assessed the quality of evidence using GRADE methods. MAIN RESULTS: Eighteen RCTs with 1250 participants met our inclusion criteria. The studies were conducted in hospital settings in low, middle and high income countries.Blood lossWe found significant reductions in blood loss with the following interventions: vaginal misoprostol (2 RCTs, 89 women: MD -97.88 ml, 95% CI -125.52 to -70.24; I(2) = 43%; moderate quality evidence); intramyometrial vasopressin (3 RCTs, 128 women: MD -245.87 ml, 95% CI -434.58 to -57.16; I(2) = 98%; moderate-quality evidence); intramyometrial bupivacaine plus epinephrine (1 RCT, 60 women: MD -68.60 ml, 95% CI -93.69 to 43.51; low-quality evidence); intravenous tranexamic acid (1 RCT, 100 women: MD 243 ml, 95% CI -460.02 to -25.98; low-quality evidence); gelatin-thrombin matrix (1 RCT, 50 women: MD -545.00 ml, 95% CI -593.26 to -496.74; low-quality evidence); intravenous ascorbic acid (1 RCT, 102 women: MD -411.46 ml, 95% CI 502.58 to -320.34; low-quality evidence); vaginal dinoprostone (1 RCT, 108 women: MD -131.60 ml, 95% CI -253.42 to -9.78; low-quality evidence); loop ligation of the myoma pseudocapsule (1 RCT, 70 women: MD -305.01 ml, 95% CI -354.83 to 255.19; low-quality evidence); and a fibrin sealant patch (1 RCT, 70 women: MD 26.50 ml, 95% CI -44.47 to -8.53; low-quality evidence). We found evidence of significant reductions in blood loss with a polyglactin suture (1 RCT, 28 women: MD -1870.0 ml, 95% CI -2547.16 to 1192.84) or a Foley catheter (1 RCT, 93 women: MD -240.70 ml, 95% CI -359.61 to -121.79) tied around the cervix. However, pooling data from these peri-cervical tourniquet RCTs revealed significant heterogeneity of the effects (2 RCTs, 121 women: MD (random) -1019.85 ml, 95% CI 2615.02 to 575.32; I(2) = 95%; low-quality evidence). There was no good evidence of an effect on blood loss with oxytocin, morcellation or clipping of the uterine artery.Need for blood transfusion We found significant reductions in the need for blood transfusion with vasopressin (2 RCTs, 90 women: OR 0.15, 95% CI 0.03 to 0.74; I(2) = 0%; moderate-quality evidence); peri-cervical tourniquet (2 RCTs, 121 women: OR 0.09, 95% CI 0.01 to 0.84; I(2) = 69%; low-quality evidence); gelatin-thrombin matrix (1 RCT, 100 women: OR 0.01, 95% CI 0.00 to 0.10; low quality evidence) and dinoprostone (1 RCT, 108 women: OR 0.17, 95% CI 0.04 to 0.81; low-quality evidence), but no evidence of effect on the need for blood transfusion with misoprostol, oxytocin, tranexamic acid, ascorbic acid, loop ligation of the myoma pseudocapsule and a fibrin sealant patch.There were insufficient data on the adverse effects and costs of the different interventions. AUTHORS' CONCLUSIONS: At present there is moderate-quality evidence that misoprostol may reduce bleeding during myomectomy, and low-quality evidence that bupivacaine plus epinephrine, tranexamic acid, gelatin-thrombin matrix, a peri-cervical tourniquet, ascorbic acid, dinoprostone, loop ligation and a fibrin sealant patch may reduce bleeding during myomectomy. There is no evidence that oxytocin, morcellation and temporary clipping of the uterine artery reduce blood loss. Further well designed studies are required to establish the effectiveness, safety and costs of different interventions for reducing blood loss during myomectomy. PMID- 25125319 TI - Which one is associated with nonalcoholic fatty liver disease? Small muscle mass or large fat mass. PMID- 25125318 TI - Complete remission of paraneoplastic vanishing bile duct syndrome after the successful treatment of Hodgkin's lymphoma: a case report and review of the literature. AB - BACKGROUND: Vanishing bile duct syndrome has been associated with different pathologic conditions (adverse drug reactions, autoimmune diseases, graft versus host disease, and cancer). Though its causes are unknown, an immune-related pathogenesis is the most likely one. Vanishing bile duct syndrome can evolve to hepatic failure and, eventually, to death. The treatment is uncertain, but it needs the resolution of the underlying pathologic condition. CASE PRESENTATION: We describe the association of Hodgkin's lymphoma with a syndrome characterized by cholestasis, aminotransferase elevation and an histological picture of bile duct loss. All other causes of hepatic function impairment were excluded (in particular, drugs, viral and autoimmune related diseases) eventually leading to the diagnosis of vanishing bile duct syndrome. Despite the fact that the dysfunction is not caused by hepatic Hodgkin's lymphoma involvement, liver impairment can limit the optimal therapy of Hodgkin's lymphoma. A treatment consisting of ursodeoxycholic acid, prednisone, and full dose chemotherapy restored hepatic function and achieved complete and long-lasting remission of Hodgkin's lymphoma. CONCLUSION: We reviewed all case reports showing that vanishing bile duct syndrome is a dismal paraneoplastic syndrome being fatal in a high proportion of patients if not adequately treated. Indeed, this syndrome requires both an early recognition and an appropriate aggressive treatment consisting of full dose upfront chemotherapy which is the only way to achieve a resolution of the vanishing bile duct syndrome. Delayed or reduced intensity treatments unfavorably correlate with survival. PMID- 25125321 TI - Perception of e-cigarette harm and its correlation with use among U.S. adolescents. AB - INTRODUCTION: U.S. adolescents increasingly use e-cigarettes. The perceived harm of e-cigarettes has not been described, nor has the correlation between harm perception and e-cigarette use been assessed. This study examines correlates of e cigarette harm perception and use of e-cigarettes in a national survey. METHODS: We used cross-sectional nationally representative data from the 2012 National Youth Tobacco Survey (n = 24,658). Cross-tabulations and multivariate ordered probit and logistic regression models were employed to assess relative harm perception and e-cigarette use. RESULTS: Half of U.S. adolescents had heard of e cigarettes. Of these, 13.2% (95% confidence interval [CI] = 11.7-14.9) and 4.0% (95% CI = 3.4-4.7) reported ever or currently using e-cigarettes, respectively. Of those aware of e-cigarettes, 34.2% (95% CI = 32.8-35.6) believed e-cigarettes were less harmful than cigarettes. Among those trying e-cigarettes, 71.8% (95% CI = 69.0-74.5) believed e-cigarettes were comparatively less harmful. Females and those >= 17 years old were more likely to perceive e-cigarettes as more harmful relative to cigarettes, while on average Whites, users of other tobacco products, and those with family members who used tobacco were more likely to perceive e cigarettes as comparatively safer. Among cigarette-naive e-cigarette users, use of other tobacco products and perceived harm reduction by e-cigarettes were, respectively, on average associated with 1.6 and 4.1 percentage-point increases in e-cigarette use. CONCLUSIONS: Perception of e-cigarettes as less harmful than conventional cigarettes was associated with increased e-cigarette use, including among cigarette-naive e-cigarette users. These findings should prompt further scientific investigation and merit attention from regulators. PMID- 25125323 TI - One-pot consecutive catalysis by integrating organometallic catalysis with organocatalysis. AB - The present study integrates two types of catalysis, namely, organometallic catalysis and organocatalysis in one reaction pot. In this process, the product of the first catalytic cycle acts as catalytic component for next catalytic cycle. The abnormal N-heterocyclic carbene-copper-based organometallic catalyst acts as an efficient catalyst for a click reaction to provide triazole, which, in turn, acts as an efficient organocatalyst for different organic transformations, for example, aza-Michael addition and multicomponent reactions, in a consecutive fashion in the same reaction pot. PMID- 25125320 TI - Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis B patients who achieved complete viral suppression with oral nucleos(t)ide analogs. AB - BACKGROUND: The durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression. METHODS: Ninety five CHB patients who showed complete virologic suppression were withdrawn from NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients, respectively. Consolidation therapy was given for 6 and 12 months for HBeAg positive and -negative CHB, respectively, before cessation. Virologic relapse was managed with the same NA that had induced complete virologic response before discontinuation. RESULTS: The cumulative rates of virologic relapse at 12 and 24 months were 73.8% and 87.1%, respectively. The relapse rates were independent of HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate analysis, duration of oral NA therapy was the only significant predicting factor associated with off-treatment virologic relapse. Although the majority of patients regained complete virologic suppression, some patients did not respond to re-treatment with the initial NA and developed genotypic resistance. CONCLUSIONS: NA consolidation therapy for 6 and 12 months is associated with high off-treatment virologic relapse in HBeAg-positive and -negative CHB patients, respectively. Drugs with high genetic barriers to resistance should be considered as a rescue therapy for off-treatment relapse in CHB. PMID- 25125322 TI - Prevalence and determinants of secondhand smoke exposure among women in Bangladesh, 2011. AB - BACKGROUND AND OBJECTIVES: The population of Bangladesh is highly susceptible to secondhand smoke (SHS) exposure due to high smoking rates and low awareness about the harmful effects of SHS. This study aims to determine the prevalence of SHS exposure and highlight the essential determinants in developing successful strategies to prevent adverse health effects in Bangladesh. METHODS: The analysis is based on the Bangladesh Demographic Health Survey 2011, in which 17,749 women in the reproductive age group (12-49 years) were included. The information regarding SHS exposure at home was derived from the question: "How often does anyone smoke inside your house?" The variable was recoded into 3 groups: daily exposure, low exposure (exposed weekly, monthly, or less than monthly), and no SHS exposure. We performed descriptive and bivariable analyses and multinomial logistic regression. RESULTS: A total of 46.7% of the women reported high exposure to SHS at home. According to the multinomial logistic regression model, relatively lower education and lower wealth index were significantly associated with daily SHS exposure at home. The exposure differed significantly between the divisions of Bangladesh. Having children at home (vs. not) and being Islamic (compared to other religious affiliations) were protective factors. CONCLUSIONS: The study indicates that women from socioeconomically disadvantaged households are more likely to experience daily exposure to SHS at home. Therefore, especially these groups have to be targeted to reduce tobacco consumption. In addition to aspects of legislation, future strategies need to focus educational aspects to improve the population's health status in Bangladesh. PMID- 25125328 TI - How are we managing sudden sensorineural hearing loss in the United Kingdom?: our experience. PMID- 25125325 TI - MRS water resonance frequency in childhood brain tumours: a novel potential biomarker of temperature and tumour environment. AB - (1)H MRS thermometry has been investigated for brain trauma and hypothermia monitoring applications but has not been explored in brain tumours. The proton resonance frequency (PRF) of water is dependent on temperature but is also influenced by microenvironment factors, such as fast proton exchange with macromolecules, ionic concentration and magnetic susceptibility. (1)H MRS has been utilized for brain tumour diagnostic and prognostic purposes in children; however, the water PRF measure may provide complementary information to further improve characterization. Water PRF values were investigated from a repository of MRS data acquired from childhood brain tumours and children with apparently normal brains. The cohort consisted of histologically proven glioma (22), medulloblastoma (19) and control groups (28, MRS in both the basal ganglia and parietal white matter regions). All data were acquired at 1.5 T using a short TE (30 ms) single voxel spectroscopy (PRESS) protocol. Water PRF values were calculated using methyl creatine and total choline. Spectral peak amplitude weighted averaging was used to improve the accuracy of the measurements. Mean PRF values were significantly larger for medulloblastoma compared with glioma, with a difference in the means of 0.0147 ppm (p < 0.05), while the mean PRF for glioma was significantly lower than for the healthy cohort, with a difference in the means of 0.0061 ppm (p < 0.05). This would suggest the apparent temperature of the glioma group was ~1.5 degrees C higher than the medulloblastomas and ~0.7 degrees C higher than a healthy brain. However, the PRF shift may not reflect a change in temperature, given that alterations in protein content, microstructure and ionic concentration contribute to PRF shifts. Measurement of these effects could also be used as a supplementary biomarker, and further investigation is required. This study has shown that the water PRF value has the potential to be used for characterizing childhood brain tumours, which has not been reported previously. PMID- 25125326 TI - Probing the size limit for nanomedicine penetration into Burkholderia multivorans and Pseudomonas aeruginosa biofilms. AB - Encapsulation of antibiotics into nanoparticles is a potential strategy to eradicate biofilms. To allow further optimization of nanomedicines for biofilm eradication, the influence of the nanoparticle size on the penetration into dense biofilm clusters needs to be investigated. In the present study, the penetration of nanoparticles with diameters ranging from 40 to 550 nm into two biofilms, Burkholderia multivorans LMG 18825 and Pseudomonas aeruginosa LMG 27622, was evaluated using confocal microscopy. Through image analysis, the percentage of particles able to penetrate into dense biofilm clusters was calculated. The size cut off for optimal penetration into biofilm clusters was located around 100-130 nm for both biofilms. The mesh size of the biofilm matrix and the size of the channels in between the bacteria of the clusters are two factors which likely play a role in the exclusion of the larger particles. For B. multivorans, a sharp drop in the penetration into the clusters is seen for particles larger than 130 nm while for P. aeruginosa, a more gradual decrease in penetration could be observed. The overall penetration of the nanoparticles was slightly lower for P. aeruginosa than for B. multivorans. Based on these results, it could be concluded that nanocarriers of about 100 nm and smaller are good candidates to improve the treatment of chronic pulmonary biofilms in CF patients. Furthermore, the confocal microscopy method demonstrated here is a useful tool to assess the penetration of nanomedicines in biofilm clusters. Such information is important to optimize nanomedicine formulations for the treatment of biofilm infections. PMID- 25125327 TI - Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: an additional barrier to non viral gene delivery. AB - Autophagy or 'self-eating' is a process by which defective organelles and foreign material can be cleared from the cell's cytoplasm and delivered to the lysosomes in which degradation occurs. It remains an open question, however, whether nanoparticles that did not enter the cell through endocytosis can also be captured from the cytoplasm by autophagy. We demonstrate that nanoparticles that are introduced directly in the cytoplasm of the cells by microinjection, can trigger an autophagy response. Moreover, both polystyrene beads and plasmid DNA containing poly-ethylene-imine complexes colocalize with autophagosomes and lysosomes, as was confirmed by electron microscopy. This indicates that cytoplasmic capturing of nanoparticles can occur by an autophagy response. The capturing of nanoparticles from the cytoplasm most likely limits the time frame in which efficient nucleic acid delivery can be obtained. Hence, autophagy forms an additional barrier to non-viral gene delivery, a notion that was not often taken into account before. Furthermore, these findings urge us to reconsider the idea that a single endosomal escape event is sufficient to have the long-lasting presence of nanoparticles in the cytoplasm of the cells. PMID- 25125329 TI - Effect of labor on plasma concentrations and postpartum clearance of cell-free, pregnancy-associated, placenta-specific microRNAs. AB - OBJECTIVE: This study aimed to investigate the effect of labor on plasma concentrations of cell-free, pregnancy-associated, placenta-specific microRNAs (miRNAs) before and after delivery. METHOD: In the non-labor group (32 women), cesarean section (C/S) was performed before the beginning of labor. In the labor group (32 women), C/S was performed after the beginning of labor. Plasma concentrations of cell-free, pregnancy-associated, placenta-specific miRNAs (miR 515-3p, miR-517a, miR-517c, and miR-518b) were measured by real-time quantitative PCR. Each miRNA concentration was compared between the non-labor and labor groups. RESULTS: Before C/S, plasma concentrations of cell-free, pregnancy associated, placenta-specific miRNAs in the labor group were significantly higher than those in the non-labor group (P = 0.001 for 515-3p, P = 0.002 for 517a, P = 0.001 for 517c, and P = 0.003 for 518b). Twenty-four hours after delivery, plasma concentrations of cell-free, pregnancy-associated, placenta-specific miRNAs in the labor group were significantly higher than those in the non-labor group (P = 0.002 for 515-3p, P = 0.017 for 517a, P = 0.043 for 517c, and P = 0.009 for 518b). CONCLUSION: The presence of labor affects cell-free, pregnancy-associated, placenta-specific miRNA levels in maternal plasma. Labor also affects postpartum clearance of these miRNAs 24 h after delivery. PMID- 25125330 TI - Neural drive to respiratory muscles in the spontaneously breathing rat pup. AB - The neonatal rodent serves as useful and appropriate model within which to study respiratory system development. Despite an extensive literature that documents respiratory control in vitro, in vivo studies have relied upon whole body plethysmography to determine measures of respiratory frequency and tidal volume. However, plethysmography restricts access to the animal and thus, respiratory muscle electromyographic (EMG) activities have not been recorded in these studies previously. Electromyography yields accurate information about neural respiratory center output to the musculature and therefore, about the control of breathing in the intact animal. In this case, we documented neural drive to respiratory pump and upper airway muscles, electrocardiogram (ECG) and chest wall motions in rat pups up to 10 days of age noting sighs, spontaneous central apneas and hypopneas in room air and with successive increments in fractional inspired CO2 (FICO2). Our findings underscore the advantages of EMG recordings for purposes of determining the magnitude and distribution of neural drive to respiratory muscles and for characterizing the full range of breathing behaviors exhibited by rats in the early postnatal period. PMID- 25125331 TI - In reference to Snoring and carotid artery intima-media thickness. PMID- 25125333 TI - Practical aspects of monochromators developed for transmission electron microscopy. AB - A few practical aspects of monochromators recently developed for transmission electron microscopy are briefly reviewed. The basic structures and properties of four monochromators, a single Wien filter monochromator, a double Wien filter monochromator, an omega-shaped electrostatic monochromator and an alpha-shaped magnetic monochromator, are outlined. The advantages and side effects of these monochromators in spectroscopy and imaging are pointed out. A few properties of the monochromators in imaging, such as spatial or angular chromaticity, are also discussed. PMID- 25125332 TI - Trehalose alleviates PC12 neuronal death mediated by lipopolysaccharide stimulated BV-2 cells via inhibiting nuclear transcription factor NF-kappaB and AP-1 activation. AB - Inflammation is implicated in the pathogenesis of Parkinson's disease (PD). Trehalose is a disaccharide which exhibits a variety of effects like anti aggregation, autophagy enhancement in PD. It has also been known to suppress inflammation in many experimental models, involving endotoxin shock, murine dry eye and subarachnoid hemorrhage. However, whether trehalose has an anti inflammation effect on PD is largely unknown. In the present study, we found trehalose inhibited generation of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and nitric oxide in the conditioned medium released from lipopolysaccharide (LPS)-stimulated BV-2 cells. LPS-induced nuclear transcription factors of NF-kappaB and AP-1 activation were also inhibited by trehalose. Then the conditioned medium of BV-2 cells was applied to PC12 neurons. As a result, both MTT and LDH indicated that trehalose decreased PC12 neuronal death. TUNEL assay showed that trehalose suppressed apoptosis of PC12 neurons. These results implied that trehalose exerted a protective effect on PC12 neurons against the neurotoxic effect triggered by BV-2 microglial activation through inhibiting NF kappaB and AP-1 activation and inflammatory mediators and cytokines production in BV-2 cells. PMID- 25125335 TI - Proteasome inhibitors with photocontrolled activity. AB - Proteasome inhibitors are widely used in cancer treatment as chemotherapeutic agents. However, their employment often results in severe side effects, due to their non-specific cytotoxicity towards healthy tissue. This problem might be overcome by using a photopharmacological approach, that is, by attaining external, dynamic, spatiotemporal photocontrol over the activity of a cytotoxic agent, achieved by the introduction of a photoswitchable moiety into its molecular structure. Here we describe the design, synthesis, and activity of photoswitchable proteasome inhibitors. Substantial differences in proteasome inhibitory activity in cell extracts were observed before and after irradiation with light. The presented results show potential for the development of chemotherapeutic agents that can be switched on and off with light, constituting a new strategy for spatiotemporally modulating proteasomal activity. PMID- 25125334 TI - Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency. AB - Methylmalonyl-CoA mutase (MUT) is an essential enzyme in propionate catabolism that requires adenosylcobalamin as a cofactor. Almost 250 inherited mutations in the MUT gene are known to cause the devastating disorder methylmalonic aciduria; however, the mechanism of dysfunction of these mutations, more than half of which are missense changes, has not been thoroughly investigated. Here, we examined 23 patient missense mutations covering a spectrum of exonic/structural regions, clinical phenotypes, and ethnic populations in order to determine their influence on protein stability, using two recombinant expression systems and a thermostability assay, and enzymatic function by measuring MUT activity and affinity for its cofactor and substrate. Our data stratify MUT missense mutations into categories of biochemical defects, including (1) reduced protein level due to misfolding, (2) increased thermolability, (3) impaired enzyme activity, and (4) reduced cofactor response in substrate turnover. We further demonstrate the stabilization of wild-type and thermolabile mutants by chemical chaperones in vitro and in bacterial cells. This in-depth mutation study illustrates the tools available for MUT enzyme characterization, guides future categorization of further missense mutations, and supports the development of alternative, chaperone-based therapy for patients not responding to current treatment. PMID- 25125336 TI - Osteoclast inhibition impairs chondrosarcoma growth and bone destruction. AB - Because Chondrosarcoma is resistant to available chemotherapy and radiation regimens, wide resection is the mainstay in treatment, which frequently results in high morbidity and which may not prevent local recurrence. There is a clear need for improved adjuvant treatment of this malignancy. We have observed the presence of osteoclasts in the microenvironment of chondrosarcoma in human pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone histologically and radiographically for bone destruction and tumor growth. At three weeks, tumors invaded local bone causing cortical disruption and trabecular resorption. Bone destruction was accompanied by increased osteoclast number and resorbed bone surface. Treatment of rats with the zoledronic acid prevented cortical destruction, inhibited trabecular resorption, and resulted in decreased tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not off-target effects of drug, was responsible for the prevention of tumor growth and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced bone destruction and tumor growth were impaired in osteopetrotic bone compared with control bone. The results from our animal model demonstrate that osteoclasts contribute to chondrosarcoma-mediated bone destruction and tumor growth and may represent a therapeutic target in particular chondrosarcoma patients. PMID- 25125337 TI - Novel MTCYB mutation in a young patient with recurrent stroke-like episodes and status epilepticus. AB - The acronym "MELAS" (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) denotes patients with histological, biochemical and/or molecular evidence of mitochondrial disease who experience stroke-like episodes. Here we report on a girl with repeated stroke-like episodes and status epilepticus, who was diagnosed with MELAS due to a novel mitochondrial cytochrome b gene (MTCYB) mutation (m.15092G>A, which predicts p.G116S). Western blotting and in silico analyses suggested that this mutation could affect the stability of complex III. Cytochrome b is the only mtDNA-encoded subunit of respiratory chain complex III. Mutations in MTCYB have been associated with isolated mitochondrial myopathy and exercise intolerance, and rarely with multisystem and/or central nervous system involvement. If the m.3243A>G and other common MELAS mutations are absent in several tissues, MTCYB should be sequenced from muscle in patients with stroke-like episodes, especially if muscle histology does not support a mitochondrial myopathy and lactic acidosis is absent. PMID- 25125338 TI - Type 1 diabetes mellitus. Comparison between the association with PTPN22 genotype and the association with ACP1-ADA1 joint genotype. AB - AIMS: T1D has been found associated with PTPN22 and with ACP1-ADA1 joint genotype. In the present note we have collected further data to evaluate the relative importance of the two systems and to search for possible interaction of PTPN22 with ACP1-ADA1 joint genotype. METHODS: We have studied 314 children with T1D and 770 controls from the White population of Central Italy. ACP1, ADA1 and PTPN22 genotypes were determined by DNA analysis. Chi square test of independence was performed by SPSS program and three way contingency analysis by a log-linear model. RESULTS: Both carriers of *T allele of PTPN22 and subjects with ACP1 *A/*A and *A/*B genotypes carrying ADA1 *2 allele show an increase of susceptibility to T1D. There is evidence of additive effect (p=0.0002) but not of epistatic interaction. The association of T1D with ACP1-ADA1 joint genotype is stronger (OR=2.494, 95% C.I. 1.509-4.122) as compared to that with PTPN22 (OR=1.825, 95% C.I. 1.951-2.859). CONCLUSIONS: It has been suggested that the *T variant of PTPN22 inhibits T cell receptor signaling leading to failure to delete autoreactive T cells during intrathymic selection resulting in increased susceptibility to autoimmune disorders. The joint genotype ACP1 *A/*A and *A/*B carrying the ADA1 *2 allele shows a decreased activity of ACP1 resulting in a lowering of Zap70 activity that may decrease T cell receptor signaling with an additive effects to the inhibition due to the *T variant of PTPN22. PMID- 25125340 TI - Isolated hepatic perfusion with oxaliplatin combined with 100 mg melphalan in patients with metastases confined to the liver: A phase I study. AB - AIM: To improve isolated hepatic perfusion (IHP), we performed a phase I dose escalation study to determine the optimal oxaliplatin dose in combination with a fixed melphalan dose. METHODS: Between June 2007 and July 2008, 11 patients, comprising of 8 colorectal cancer and 3 uveal melanoma patients and all with isolated liver metastases, were treated with a one hour IHP with escalating doses of oxaliplatin combined with 100 mg melphalan. Samples of blood and perfusate were taken during IHP treatment for pharmacokinetic analysis of both drugs and patients were monitored for toxicity, response and survival. RESULTS: Dose limiting sinusoidal obstruction syndrome (SOS) occurred at 150 mg oxaliplatin. The areas under the concentration-time curves (AUC) of oxaliplatin at the maximal tolerated dose (MTD) of 100 mg oxaliplatin ranged from 11.9 mg/L h to 16.5 mg/L h. All 4 patients treated at the MTD showed progressive disease 3 months after IHP. CONCLUSIONS: In view of similar and even higher doses of oxaliplatin applied in both systemic treatment and hepatic artery infusion (HAI), applying this dose in IHP is not expected to improve treatment results in patients with isolated hepatic metastases. PMID- 25125339 TI - The DEXLIFE study methods: identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals. AB - The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is likely to affect 592 million people in 2035 if the current rate of progression is continued. Today, patients are diagnosed with T2D based on elevated blood glucose, either directly or indirectly (HbA1c). However, the information on disease progression is limited. Therefore, there is a need to identify novel early markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. In the DEXLIFE study, several clinical cohorts provide the basis for a series of clinical, physiological and mechanistic investigations in combination with a range of--omic technologies to construct a detailed metabolic profile of high-risk individuals across multiple cohorts. In addition, an exercise and dietary intervention study is conducted, that will assess the impact on both plasma biomarkers and specific functional tissue-based markers. The DEXLIFE study will provide novel diagnostic and predictive biomarkers which may not only effectively detect the progression towards diabetes in high risk individuals but also predict responsiveness to lifestyle interventions known to be effective in the prevention of diabetes. PMID- 25125341 TI - A comparison of fibrin sealant versus standard closure in the reduction of postoperative morbidity after groin dissection: A systematic review and meta analysis. AB - BACKGROUND: Groin dissection is commonly performed in patients with lower limb malignant conditions such as malignant melanoma, vulvar, penile, anal and scrotal carcinomas with an associated high complication rate. Numerous surgical strategies have been suggested to reduce morbidity. We aimed to systematically review one of those methods - fibrin sealant (FS) - in comparison to standard closure (SC) in reducing postoperative morbidity from groin dissection. METHODS: A systematic search of the literature, study selection and data extraction using an independent screening process, assessment of risk of bias and statistical data analysis was performed. Only randomised controlled trials (RCTs) comparing fibrin sealant to standard care in patients with malignant disease undergoing groin dissection reporting at least one outcome measure relating to postoperative complications were included in the review. RESULTS: A total of 6 RCTs were included. There were no statistically significant differences in postoperative surgical site infection (SSI) rates between FS and SC. The overall incidence of wound infection in the FS group was 32% (43/133) compared to 34% (45/132) in the SC group. (Pooled risk ratio = 0.0.94 [0.68, 1.32]; 95% CI; P = 0.74). The incidence of seroma for the FS group (30/133) and the SC group (30/132) did not differ (Pooled risk ratio = 1.03 [0.67, 1.58]; 95% CI; P value = 0.90). Complication rates were similar between groups. CONCLUSION: Based on current evidence, fibrin sealant does not significantly reduce morbidity in patients undergoing groin dissection for the management of malignant disease when compared to standard closure techniques. PMID- 25125343 TI - Next-generation sequence testing expands research into causes of hearing loss: scientists examine role of multiple mutations in individual cases. PMID- 25125344 TI - Newborn bloodspot retention reinstated in Minnesota: practice expected to benefit larger newborn screening studies, public health, disease research. PMID- 25125342 TI - Anatomy and ontogeny of a novel hemodynamic organ in zebrafish. AB - The zebrafish maxillary barbel can protract and retract in response to stimuli, and appears connected to a prominent blood sinus on the lateral aspect of the maxillary bone. However, the mechanism of barbel movement is not described. Using whole-mount phalloidin staining of the sinus region, we observed long filamentous actin cables, suggesting highly organized vascular smooth muscle cells, surrounding an endothelial chamber. Although the chamber is variably filled by erythrocytes in vivo, cardiac injection of fluorescent dextrans shows that it consistently contains plasma. Full-thickness confocal imaging of dextran-injected adults containing EGFP(+) endothelial cells revealed a vascular complex with three compartments, here named the distal bulb, central chamber, and accessory chamber. The early ontogeny of all three compartments was confirmed in a whole mount series of Tg(fli1a:EGFP) juveniles. In wild type adults, the fine structure of each chamber was studied using paraffin- and plastic-section histochemistry and transmission electron microscopy. The distal bulb and central chamber have smooth muscle coats with luminally-elongated septa, forming semi-detached blood filled lacunae. The central chamber walls and septa are extensively innervated by small, unmyelinated axons, as confirmed by immunohistochemical detection of acetylated tubulin, a component of axonal cytoplasm. The accessory chamber appears neither innervated nor muscularized, but is an endothelial cul-de-sac with a thickened elastic adventitia, suggesting an extensible fluid reservoir. We propose that we have identified a new organ in zebrafish, the maxillary barbel blood sinus, whose neurovascular specializations may contribute to zebrafish sensory biology and appendage control. PMID- 25125346 TI - May the thyroid gland and thyroperoxidase participate in nitrosylation of serum proteins and sporadic Parkinson's disease? AB - The research group has detected nitrosative stress and a singular version of nitrosylated serum alpha-synuclein in serum of Parkinson's disease (PD) patients. Dysfunction of the thyroid gland has been proposed to be linked to this disease. The aim of the study was to know if the thyroid gland is involved in idiopathic PD and nitrosative stress. We studied 50 patients (early and advanced disease patients), 35 controls, and 6 subjects with thyroidectomy. Clinical characteristics, serum thyroperoxidase levels, and 3-nitrotyrosine proteins were analyzed. Enzyme-linked immunosorbent assay and immunoblotting methods were employed. The findings indicated that the prevalence of two thyroid dysfunctions (hyper- or hypothyroidism) was not found to be different in patients relative to controls. However, the levels of the enzyme thyroperoxidase were found to be elevated in early disease patients (p<0.006), not in advanced disease subjects, and these levels were negatively correlated with serum 3-nitrotyrosine proteins (p<0.05), the indicators of nitrosative stress. The thyroidectomized subjects showed very low levels of serum 3-nitrotyrosine proteins (78% reduction vs. controls) and, among these proteins, the nitrosylated serum alpha-synuclein was nearly absent. These observations lead to the hypothesis that the thyroid gland and thyroperoxidase participate in nitrosylation of serum proteins and they could influence Parkinsonian nitrosative stress as well as nitrosylation of serum alpha synuclein, a potentially pathogenic factor. PMID- 25125347 TI - Combining serum carbohydrate-deficient transferrin and hair ethyl glucuronide to provide optimal information on alcohol use. PMID- 25125348 TI - Detoxifying polyhalogenated catechols through a copper-chelating agent by forming stable and redox-inactive hydrogen-bonded complexes with an unusual perpendicular structure. AB - The use of selective metal chelating agents with preference for binding of a specific metal ion to investigate its biological role is becoming increasingly common. We found recently that a well-known copper-specific chelator 2,9-dimethyl 1,10-phenanthroline (2,9-Me2OP) could completely inhibit the synergistic toxicity induced by tetrachlorocatechol (TCC) and sodium azide (NaN3). However, its underlying molecular mechanism is still not clear. Here, we show that the protection by 2,9-Me2OP is not due to its classic copper-chelating property, but rather due to formation of a multiple hydrogen-bonded complex between 2,9-Me2OP and TCC, featuring an unusual perpendicular arrangement of the two binding partners. The two methyl groups at the 2,9 positions in 2,9-Me2OP were found to be critical to stabilize the 2,9-Me2OP/TCC complex due to steric hindrance, and therefore completely prevents the generation of the reactive and toxic semiquinone radicals by TCC/NaN3. This represents the first report showing that an unexpected new protective mode of action for the copper "specific" chelating agent 2,9-Me2OP by using its steric hindrance effect of the two CH3 groups not only to chelate copper, but also to "chelate" a catechol through multiple H bonding. These findings may have broad biological implications for future research of this widely used copper-chelating agent and the ubiquitous catecholic compounds. PMID- 25125350 TI - Controlled release of therapeutic antibody formats. AB - The local administration of antibodies can represent in many cases a significant improvement for antibody-based therapies. The benefits of local delivery include high drug concentrations at the target site, the possibility of lower drug dosing and less systemic drug exposure. Currently, the most relevant delivery sites for therapeutic antibodies are the posterior segments of the eye, mucosal surfaces, the articular joints and the central nervous system (CNS). In addition, the oral and pulmonary route may enable non-invasive systemic antibody delivery. However, local antibody delivery to these sites is characterized by short drug residence times and a low compliance of administration. Controlled release (CR) systems can address these limitations and, thereby, enable and improve local delivery applications by achieving long lasting local drug concentrations, improved efficacy-dosing ratios and reduced treatment-associated side effects. The requirements for CR antibody formulations are more complex compared to conventional CR systems for small molecules, and their development poses an enormous technical challenge. Therefore, the review highlights experiences and challenges gathered in the development of the different CR systems for antibodies to date. Additionally, the unmet technological needs encountered in the field are described. This includes a critical evaluation of the limited capability of various CR systems to preserve antibody stability, delivery site specific considerations, as well as the processability of a CR system with a particular focus on drug loading and injectability. We believe that the success of CR and local delivery approaches could create an enormous added value for patients in the future. PMID- 25125349 TI - Effects of a eucaloric reduced-carbohydrate diet on body composition and fat distribution in women with PCOS. AB - OBJECTIVE: To determine if consumption of a reduced-carbohydrate (CHO) diet would result in preferential loss of adipose tissue under eucaloric conditions, and whether changes in adiposity were associated with changes in postprandial insulin concentration. METHODS: In a crossover-diet intervention, 30 women with PCOS consumed a reduced-CHO diet (41:19:40% energy from CHO:protein:fat) for 8 weeks and a standard diet (55:18:27) for 8 weeks. Body composition by DXA and fat distribution by CT were assessed at baseline and following each diet phase. Insulin AUC was obtained from a solid meal test (SMT) during each diet phase. RESULTS: Participants lost 3.7% and 2.2% total fat following the reduced-CHO diet and STD diet, resp. (p<0.05 for difference between diets). The reduced-CHO diet induced a decrease in subcutaneous-abdominal, intra-abdominal, and thigh intermuscular adipose tissue (-7.1%, -4.6%, and -11.5%, resp.), and the STD diet induced a decrease in total lean mass. Loss of fat mass following the reduced CHO diet arm was associated with lower insulin AUC (p<0.05) during the SMT. CONCLUSIONS: In women with PCOS, consumption of a diet lower in CHO resulted in preferential loss of fat mass from metabolically harmful adipose depots, whereas a diet high in CHO appeared to promote repartitioning of lean mass to fat mass. PMID- 25125351 TI - The key role of caregiver confidence in the caregiver's contribution to self-care in adults with heart failure. AB - BACKGROUND: Caregivers play an important role in contributing to heart failure (HF) patients' self-care but no prior studies have examined the caregivers' contributions to HF patients' self-care and no prior studies have examined potential determinants of the caregivers' contribution to HF patients' self-care. AIMS: The purpose of this study was to describe the caregivers' contribution to HF patients' self-care and identify its determinants. METHODS: The study design involved a secondary analysis of cross-sectional data. Caregivers' contributions were measured with the Caregiver's Contribution to Self-care of HF Index (CC SCHFI) which measures the caregiver's contribution to self-care maintenance and management and caregiver confidence in contributing to HF patient's self-care. Potential determinants were measured using a socio-demographic questionnaire completed by caregivers and patients, and patient clinical data was obtained from the medical record. RESULTS: Data from 515 caregiver/patient dyads were analyzed. Most (55.5%) patients were male (mean age 75.6 years) and most (52.4%) caregivers were female (mean age, 56.6 years). The caregivers' contribution to patients' self-care maintenance was low in weight monitoring and physical activity but higher in checking ankles, advising on low-salt foods and taking medicines. The caregivers' contribution to patients' self-care management was low in symptom recognition. When symptoms were recognized, caregivers advised patients to reduce fluids and salt and call the provider but rarely advised to take an extra diuretic. Caregiver confidence in the ability to contribute to patient self-care explained a significant amount of variance in the caregiver's contribution. CONCLUSION: These findings suggest that caregivers in this sample did not contribute meaningfully to HF self-care. Providers should educate both HF patients and caregivers. Interventions that improve caregiver confidence have the potential to successfully increase the caregivers' contribution to patients' self care. PMID- 25125352 TI - The caregiver role in thromboprophylaxis management in atrial fibrillation: a literature review. AB - BACKGROUND: Atrial fibrillation is a common arrhythmia and a risk factor for adverse events including stroke. People living with atrial fibrillation are commonly elderly and have multiple comorbidities. The role of a caregiver in supporting the individual to manage a chronic and complex condition has received limited attention. OBJECTIVES: This review aims to summarize available information on the caregiver role in atrial fibrillation, specifically in promoting adherence to thromboprophylaxis and evidence for strategies to support and enable the caregiver. DATA SOURCES: A review of electronic databases and search engines was undertaken including Medline, Scopus and CINAHL. The search terms 'atrial fibrillation', 'anticoagulation', 'carer', 'caregiver', 'family support' were used. Dates searched were from January 1990 to November 2012. RESULTS: The review found limited original clinical research studies. The majority of the literature identified in the initial search included review papers and work which recommends the inclusion of the caregiver in the care of patients with atrial fibrillation but limited empirical evidence. CONCLUSIONS: Caregivers have an essential role to play in advocacy, family centred care and shared decision-making. This may influence thromboprophylaxis treatment choices and potentially adherence. Assessment of caregiver needs and support should be central to patient assessment and care planning. There is a need for clinical intervention studies which more target and address the caregiver role. PMID- 25125354 TI - Liquid scintillation spectrometry: a technique with future. PMID- 25125353 TI - Post-discharge electrocardiogram Holter monitoring in recently hospitalised individuals with chronic atrial fibrillation to enhance therapeutic monitoring and identify potentially predictive phenotypes. AB - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia managed in clinical practice. Maintenance of intended rate or rhythm control following hospitalisation is a key therapeutic goal. AIMS: The purpose of this study was to assess post-discharge maintenance of intended AF control and classify potentially predictive heart rate (HR) phenotypes via electrocardiogram (ECG) Holter monitoring. METHODS: In a sub-study of a multicentre randomised controlled trial comparing AF-specific management with usual care, 24-hour ECG Holter monitoring was undertaken in 133 patients 7-14 days post-discharge. Intended rate and rhythm control were compared to Holter data. Analysis of the frequency distribution of mean hour-to-hour differences identified those with labile HRs. RESULTS: Mean age was 71 +/- 10 years, 67 (50%) were male and mean HR was 72 +/- 14 bpm. Most (89%) had persistent AF (median time in AF=39% (IQR 0 100%)). Uncontrolled HR (>90 bpm for >10% of recording) occurred in 35 (26%) patients and 49 (37%) patients did not achieve their intended rate (n=26) or rhythm control (n=23). Patients in the upper quartile of mean hour-to-hour HR variability were identified as persistently labile (n=33). A further group (n=22) with periodically labile HRs was identified. Those with coronary artery disease (OR 0.34; 95% CI 0.13-0.91, p=0.033) or renal disease/dysfunction (OR 0.24; 95% CI 0.06-0.98, p=0.047) were less likely to demonstrate HR stability (n=78). CONCLUSION: Post-discharge ECG Holter monitoring of AF patients represents a valuable tool to identify deviations in intended rhythm/rate control and adjust therapeutic management accordingly. It may also identify individuals who demonstrate labile HRs. PMID- 25125355 TI - Response to invited commentary: Methods to address control for confounding and nonperfect randomization when using outcome distribution curves to estimate the population-level impact of a public health intervention. PMID- 25125359 TI - Hong Kong: an R&D hub in Asia for materials science and engineering. PMID- 25125364 TI - Interdependencies among clinical research funders. PMID- 25125365 TI - More ethical and more efficient clinical research: multiplex trial design. AB - BACKGROUND: Today's clinical research faces challenges such as a lack of clinical equipoise between treatment arms, reluctance in randomizing for multiple treatments simultaneously, inability to address interactions and increasingly restricted resources. Furthermore, many trials are biased by extensive exclusion criteria, relatively small sample size and less appropriate outcome measures. FINDINGS: We propose a 'Multiplex' trial design that preserves clinical equipoise with a continuous and factorial trial design that will also result in more efficient use of resources. This multiplex design accommodates subtrials with appropriate choice of treatment arms within each subtrial. Clinical equipoise should increase consent rates while the factorial design is the best way to identify interactions. CONCLUSION: The multiplex design may evolve naturally from today's research limitations and challenges, while principal objections seem absent. However this new design poses important infrastructural, organisational and psychological challenges that need in depth consideration. PMID- 25125366 TI - Transcriptional activation of Fsp27 by the liver-enriched transcription factor CREBH promotes lipid droplet growth and hepatic steatosis. AB - Fat-specific protein 27 (Fsp27) is a lipid droplet-associated protein that promotes lipid droplet (LD) growth and triglyceride (TG) storage in white adipocytes. Fsp27 is also highly expressed in the steatotic liver and contributes to TG accumulation. In this study we discovered that the liver produces Fsp27beta, an alternative Fsp27 isoform, which contains 10 additional amino acids at the N-terminus of the original Fsp27 (Fsp27alpha). White adipose tissue (WAT) and the liver specifically expressed Fsp27alpha and Fsp27beta transcripts, respectively, which were driven by distinct promoters. The Fsp27beta promoter was activated by the liver-enriched transcription factor cyclic-AMP-responsive element-binding protein H (CREBH) but not by peroxisome proliferator-activated receptor gamma (PPARgamma), which activated the Fsp27alpha promoter. Enforced expression of the constitutively active CREBH strongly induced Fsp27beta and the human ortholog CIDEC2 in mouse hepatocytes and HepG2 cells, respectively. In contrast, loss of CREBH decreased hepatic Fsp27beta in fasted mice, suggesting that CREBH plays a critical role in Fsp27beta expression in the liver. Similar to Fsp27alpha, Fsp27beta localized on the surface of lipid droplets and suppressed lipolysis. Consequently, enforced expression of Fsp27beta or CREBH promoted lipid droplet enlargement and TG accumulation in the liver. CONCLUSION: The CREBH Fsp27beta axis is important for regulating lipid droplet dynamics and TG storage in the liver. PMID- 25125367 TI - Intratumor distribution and test-retest comparisons of physiological parameters quantified by dynamic contrast-enhanced MRI in rat U251 glioma. AB - The distribution of dynamic contrast-enhanced MRI (DCE-MRI) parametric estimates in a rat U251 glioma model was analyzed. Using Magnevist as contrast agent (CA), 17 nude rats implanted with U251 cerebral glioma were studied by DCE-MRI twice in a 24 h interval. A data-driven analysis selected one of three models to estimate either (1) plasma volume (vp), (2) vp and forward volume transfer constant (K(trans)) or (3) vp, K(trans) and interstitial volume fraction (ve), constituting Models 1, 2 and 3, respectively. CA distribution volume (VD) was estimated in Model 3 regions by Logan plots. Regions of interest (ROIs) were selected by model. In the Model 3 ROI, descriptors of parameter distributions- mean, median, variance and skewness--were calculated and compared between the two time points for repeatability. All distributions of parametric estimates in Model 3 ROIs were positively skewed. Test-retest differences between population summaries for any parameter were not significant (p >= 0.10; Wilcoxon signed-rank and paired t tests). These and similar measures of parametric distribution and test-retest variance from other tumor models can be used to inform the choice of biomarkers that best summarize tumor status and treatment effects. PMID- 25125370 TI - Alternative splicing regulation of APP exon 7 by RBFox proteins. AB - RBFox proteins are well-known alternative splicing regulators. We have shown previously that during neuronal differentiation of P19 cells induced by all-trans retinoic acid and cell aggregation, RBFox1 shows markedly increased temporal expression. To find its key splicing regulation, we examined the effect of RBFox1 on 33 previously reported and validated neuronal splicing events of P19 cells. We observed that alternative splicing of three genes, specifically, amyloid precursor protein (APP), disks large homolog 3 (DLG3), and G protein, alpha activating activity polypeptide O (GNAO1), was altered by transient RBFox1 expression in HEK293 and HeLa cells. Moreover, an RBFox1 mutant (RBFox1FA) that was unable to bind the target RNA sequence ((U)GCAUG) did not induce these splicing events. APP generates amyloid beta peptides that are involved in the pathology of Alzheimer's disease, and therefore we examined APP alternative splicing regulation by RBFox1 and other splicing regulators. Our results indicated that RBFox proteins promote the skipping of APP exon 7, but not the inclusion of exon 8. We made APP6789 minigenes and observed that two (U)GCAUG sequences, located upstream of exon 7 and in exon 7, functioned to induce skipping of exon 7 by RBFox proteins. Overall, RBFox proteins may shift APP from exon 7 containing isoforms, APP770 and APP751, toward the exon 7 lacking isoform, APP695, which is predominant in neural tissues. PMID- 25125369 TI - Astrocytic control of neural circuit formation: highlights on TGF-beta signaling. AB - Brain function depends critically on the coordinated activity of presynaptic and postsynaptic signals derived from both neurons and non-neuronal elements such as glial cells. A key role for astrocytes in neuronal differentiation and circuitry formation has emerged within the last decade. Although the function of glial cells in synapse formation, elimination and efficacy has greatly increased, we are still very far from deeply understanding the molecular and cellular mechanism underlying these events. The present review discusses the mechanisms driving astrocytic control of excitatory and inhibitory synapse formation in the central nervous system, especially the mechanisms mediated by soluble molecules, particularly those from the TGF-beta family. Further, we discuss whether and how human astrocytes might contribute to the acquisition of human cognition. We argue that understanding how astrocytic signals regulate synaptic development might offer new insights into human perception, learning, memory, and cognition and, ultimately, provide new targets for the treatment of neurological diseases. PMID- 25125371 TI - Reference ranges for the volumes of fetal cardiac ventricular walls by three dimensional ultrasound using spatiotemporal image correlation and virtual organ computer-aided analysis and its validation in fetuses with congenital heart diseases. AB - OBJECTIVE: To establish reference values for the volumes of fetal cardiac ventricular walls using three-dimensional ultrasonography (3DUS) and perform data validation using fetuses with confirmed congenital heart disease (CHD). METHODS: This prospective, cross-sectional study analyzed 371 singleton pregnancies between 20w0d and 33w6d of gestation. Ventricular volumes were assessed using spatiotemporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL). We calculated the polynomial regressions, adjusted by the coefficient of determination (R(2) ). To assess intra-observer concordance, the intraclass correlation coefficient (ICC) was used. To validate the curves, the ventricular wall volumes of 22 fetuses with CHD were evaluated. RESULTS: There was a good correlation between these mean volumes and gestational age, and this correlation was best represented by linear equations. Intra-observer concordance in assessing the volumes of the right (ICC = 0.90) and left ventricular walls (ICC = 0.97) was good. We observed that the volumes of the right and left ventricular walls were altered (<5(th) percentile and/or >95(th) percentile) in 8/22 fetuses presenting with CHD. CONCLUSION: The reference ranges for the volumes of the right and left ventricular walls by 3DUS using STIC and VOCAL between 20w0d and 33w6d of gestation were determinate, and they exhibited good intra-observer concordance. PMID- 25125372 TI - Elongation of amyloid fibrils through lateral binding of monomers revealed by total internal reflection fluorescence microscopy. AB - Amyloid fibrils are fibrillar aggregates of denatured proteins associated with a large number of amyloidoses. The formation of amyloid fibrils has been considered to occur by nucleation and elongation. Real-time imaging of the elongation as well as linear morphology of amyloid fibrils suggests that all elongation events occur at the growing ends of fibrils. On the other hand, we suggested that monomers also bind to the lateral sides of preformed fibrils during the seed dependent elongation, diffuse to the growing ends, and finally make further conformation changes to the mature amyloid fibrils. To examine lateral binding during the elongation of fibrils, we used islet amyloid polypeptide (IAPP), which has been associated with type II diabetes, and prepared IAPP modified with the fluorescence dye, Alexa532. By monitoring the elongation process with amyloid specific thioflavin T and Alexa532 fluorescence, we obtained overlapping images of the two fluorescence probes, which indicated lateral binding. These results are similar to the surface diffusion-dependent growth of crystals, further supporting the similarities between amyloid fibrillation and the crystallization of substances. PMID- 25125373 TI - pH-dependent antigen-binding antibodies as a novel therapeutic modality. AB - Monoclonal antibodies have become a general modality in therapeutic development. However, even with infinite binding affinity to an antigen, a conventional antibody is limited in that it can bind to the antigen only once, and this results in antigen-mediated antibody clearance when the a membrane-bound antigen is targeted, or in antibody-mediated antigen accumulation when a soluble antigen is targeted. Recently, a pH-dependent antigen-binding antibody that binds to an antigen in plasma at neutral pH and dissociates from the antigen in endosome at acidic pH has been reported to overcome this limitation and to reduce antigen mediated antibody clearance and antibody-mediated antigen accumulation. A pH dependent binding antibody against a soluble antigen can be further improved by Fc engineering to enhance the Fc receptor binding. Various approaches, including histidine-based engineering, direct cloning from immunized animals, and synthetic and combinatorial libraries, have been successfully applied to generate pH dependent binding antibodies against various antigens. This review discusses the features, approaches, advantages, and challenges of developing a pH-dependent binding antibody as a novel therapeutic modality. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. PMID- 25125368 TI - A new look at social support: a theoretical perspective on thriving through relationships. AB - Close and caring relationships are undeniably linked to health and well-being at all stages in the life span. Yet the specific pathways through which close relationships promote optimal well-being are not well understood. In this article, we present a model of thriving through relationships to provide a theoretical foundation for identifying the specific interpersonal processes that underlie the effects of close relationships on thriving. This model highlights two life contexts through which people may potentially thrive (coping successfully with life's adversities and actively pursuing life opportunities for growth and development), it proposes two relational support functions that are fundamental to the experience of thriving in each life context, and it identifies mediators through which relational support is likely to have long-term effects on thriving. This perspective highlights the need for researchers to take a new look at social support by conceptualizing it as an interpersonal process with a focus on thriving. PMID- 25125374 TI - Effectiveness of laser Doppler perfusion monitoring in the assessment of microvascular function in patients undergoing on-pump coronary artery bypass grafting. AB - OBJECTIVES: To evaluate the effectiveness of single-point laser Doppler perfusion monitoring (LDPM) in the assessment of microvascular reactivity in the skin during cardiopulmonary bypass (CPB). DESIGN: Cross-sectional observational study. SETTING: Government-affiliated teaching hospital. PARTICIPANTS: Twenty male patients aged 60 +/- 2 years who underwent coronary artery bypass grafting under CPB. INTERVENTIONS: The authors assessed the endothelium-dependent vasodilation of the skin microcirculation at the forehead and forearm using LDPM coupled with thermal hyperemia. This measurement was performed before and after the induction of anesthesia, during and after CPB, and 24 h after the end of the surgical procedure. RESULTS: The basal values of microvascular flow before the induction of anesthesia were significantly higher in the skin of the forehead compared with that of the forearm. There were no significant alterations in microvascular reactivity throughout the recording periods for both recording sites, as assessed by the vasodilation range expressed as cutaneous vascular conductance (arbitrary perfusion units/mean arterial pressure). CONCLUSIONS: Using LDPM, the authors showed that the microcirculatory bed of the skin of the forehead, which is readily accessible during cardiac surgery, is a suitable model for the study of microvascular reactivity and tissue perfusion in cardiovascular surgical procedures using CPB. This technique could, thus, be suitable for evaluating the effects of drugs or technical procedures on tissue perfusion during cardiac surgery under cardiopulmonary bypass. PMID- 25125375 TI - Influence of light curing units and fluoride mouthrinse on morphological surface and color stability of a nanofilled composite resin. AB - Composite resin is a dental material susceptible to color change over time which limits the longevity of restorations made with this material. The influence of light curing units and different fluoride mouthrinses on superficial morphology and color stability of a nanofilled composite resin was evaluated. Specimens (N = 150) were prepared and polished. The experimental groups were divided according to the type of light source (halogen and LED) and immersion media (artificial saliva, 0.05% sodium fluoride solution-manipulated, Fluordent Reach, Oral B, Fluorgard). Specimens remained in artificial saliva for 24-h baseline. For 60 days, they were immersed in solutions for 1 min. Color readout was taken at baseline and after 60 days of immersion. Surface morphology was analyzed by Scanning Electron Microscopy (SEM) after 60 days of immersion. Color change data were submitted to two-way Analysis of Variance and Tukey tests (alpha = 0.05). Surface morphology was qualitatively analyzed. The factor light source presented no significant variability (P = 0.281), the immersion media, significant variability (P < 0.001) and interaction between factors, no significant variability (P = 0.050). According to SEM observations, no difference was noted in the surface of the specimens polymerized by different light sources, irrespective of the immersion medium. It was concluded that the light source did not influence the color stability of composite, irrespective of the immersion media, and among the fluoride solutions analyzed, Fluorgard was the one that promoted the greatest color change, however, this was not clinically perceptible. The immersion media did not influence the morphology of the studied resin. PMID- 25125377 TI - Santiago Ramon y Cajal: The Cajal Institute and the Spanish Histological School. AB - Santiago Ramon y Cajal was a self-taught researcher. He almost always worked alone, usually in the solitude of his private laboratory installed at his home. He was also a university professor and therefore taught histology and pathology to many students. But because research laboratories were scarce and poorly equipped, he preferred to organize courses and tutor at home as well. For this reason, Cajal left a faint trace of disciples in the three academic chairs that he came to occupy. It may be argued that Cajal formed the histological school when the Spanish government decided to support his investigations and created a scientific laboratory for him, with funding to cover the cost of journals, instruments, materials, personnel, and so forth. This support occurred in the year 1902, after Cajal received the Moscow Prize. Some of his former students accompanied Cajal to the new laboratory. Upon receipt of new awards, including the Gold Medal of von Helmholtz (1905) and the Nobel Prize in Physiology or Medicine (1906), Cajal's popularity increased and a large number of students wanted to learn about the laboratory and work with the great Cajal. This review tells this history. But we realize that this is not an easy task because to be fair to all the people that formed the Spanish Histological School, we would need to write a book. This is not practical. Instead, selection of contributors to the formation of the Spanish Histological School is provided. At the same time, some brushstrokes of the story extend to and include the Cajal Institute, which ran in parallel with the Spanish Histological School. PMID- 25125378 TI - Impact of environmental and personality factors upon adolescents before and after psychotherapeutic intervention. AB - It is important to understand the risk factors and resilience factors that contribute to psychological distress or to a sense of well-being in adolescents. This study focuses on life events and social support from an external environmental aspect. The focus from an internal-personality aspect is on self criticism and self-disclosure. In this study, 155 adolescents, ages 12-18 years, were divided into two groups. The experimental group included 70 adolescents requesting psychotherapy for emotional disorders. The control group included 85 adolescents without emotional disorders. Participants in the experimental group were followed up to the completion of six months of psychotherapy. Adolescents in the experimental group had undergone more negative life events and a significantly smaller number of positive life events compared to the control group [F(4, 143)=9.77, p<0.001, Eta(2)=.22]. The experimental group was characterized by a diminished degree of social support compared to the control group [F(2, 144)=7.27, p<0.01, Eta(2)=.09]. Regarding self-criticism and self disclosure, no differences were found between the control and experimental groups [F(3, 148)=2.18, p>0.05, Eta(2)=.04]. The prospective analysis following six months of psychotherapy indicated a significant improvement in distress variables reported by the parents but not by the subjects themselves, pointing to the importance of family intervention as part of adolescent psychotherapy. A decrease in the level of self-criticism after psychotherapeutic intervention was found [F(1, 18)=4.41, p<0.05, Eta(2)=.20], altering self-criticism from a factor that needs to be neutralized to a factor that can be improved during psychotherapy. PMID- 25125376 TI - Functional chromatography reveals three natural products that target the same protein with distinct mechanisms of action. AB - Access to lead compounds with defined molecular targets continues to be a barrier to the translation of natural product resources. As a solution, we developed a system that uses discrete, recombinant proteins as the vehicles for natural product isolation. Here, we describe the use of this functional chromatographic method to identify natural products that bind to the AAA+ chaperone, p97, a promising cancer target. Application of this method to a panel of fungal and plant extracts identified rheoemodin, 1-hydroxydehydroherbarin, and phomapyrrolidone A as distinct p97 modulators. Excitingly, each of these molecules displayed a unique mechanism of p97 modulation. This discovery provides strong support for the application of functional chromatography to the discovery of protein modulators that would likely escape traditional high-throughput or phenotypic screening platforms. PMID- 25125379 TI - Diagnostic and clinical characteristics of early-manifesting females with Duchenne or Becker muscular dystrophy. AB - Manifestations of Duchenne and Becker muscular dystrophy (DBMD) are present in up to 40% of heterozygous females, but there are few reports of females who exhibit skeletal muscle symptoms in childhood. From the Muscular Dystrophy Surveillance Tracking and Research Network, a multi-site population-based surveillance network for dystrophinopathy, nine symptomatic female heterozygotes with onset of symptoms prior to age 9 years were identified. The median age at diagnosis was 8.3 years, and the median interval from first symptoms to diagnosis was 1.35 years. Of the nine female heterozygotes, four had a positive family history, seven had intellectual disability and five had at least one mental health disorder. Mental health concerns included attention deficit hyperactivity disorder (ADHD), autism spectrum features, bipolar disorder, and depression. The frequency of intellectual and mental health problems in this group is higher than previously reported for affected males and for symptomatic females. These findings may have implications for diagnosis of early manifesting heterozygotes and for their health supervision. PMID- 25125380 TI - Injury to the suprascapular nerve during superior labrum anterior and posterior repair: is a rotator interval portal safer than an anterosuperior portal? AB - PURPOSE: The purpose of this study was to compare the risk of injury to the suprascapular nerve during suture anchor placement in the glenoid when using an anterosuperior portal versus a rotator interval portal. METHODS: Ten bilateral fresh human cadaveric shoulders were randomized to anchor placement through the anterosuperior portal on one shoulder and the rotator interval portal on the contralateral shoulder. Standard 3 * 14 mm suture anchors were placed in the glenoid rim (1 o'clock, 11 o'clock, and 10 o'clock positions for the right shoulder). The suprascapular nerve was dissected. When glenoid perforation occurred, the distance from the anchor tip to the suprascapular nerve, the distance from the glenoid rim to the suprascapular nerve, and the drill-hole depth at each entry site were recorded. RESULTS: All far-posterior anchors perforated the glenoid rim when using the anterosuperior or rotator interval portal. The distance from the far-posterior anchor tip to the suprascapular nerve averaged 8 mm (range, 3.4 to 14 mm) for the anterosuperior portal and 2.1 mm (range, 0 to 5.5 mm) for the rotator interval portal (P <= .001). CONCLUSIONS: Using an anterosuperior or rotator interval portal results in consistent penetration of 1 o'clock and 2 o'clock posterior anchors and might place the suprascapular nerve at risk of iatrogenic injury. Based on closer proximity of the anchor tip to the suprascapular nerve, the risk of injury is significantly greater with a rotator interval portal. CLINICAL RELEVANCE: Using a rotator interval portal for suture anchor placement in the posterior aspect of the glenoid rim can lead to a higher likelihood of suprascapular nerve injury. PMID- 25125381 TI - Ligamentum teres injuries of the hip: a systematic review examining surgical indications, treatment options, and outcomes. AB - PURPOSE: Hip arthroscopy is becoming a common technique for the diagnosis and treatment of ligamentum teres pathologic conditions. This systematic review aims to determine the indications/contraindications, treatments, and surgical outcomes for management of ligamentum teres injuries. METHODS: We searched EMBASE, MEDLINE, and PubMed databases from 1946 to November 28, 2013 for all relevant English articles pertaining to surgical treatment of the ligamentum teres. A hand search of the reference sections of included articles was performed, and all relevant articles were systematically screened in duplicate, with agreement and descriptive statistics presented. RESULTS: We identified 1,016 studies, 9 of which (4 case series and 5 case reports) met our eligibility criteria. These studies had a total of 87 patients (89 hips) who had undergone either arthroscopic debridement (81 patients, 83 hips) or reconstruction with autografting, allografting, or synthetic grafting (6 patients) of a torn ligamentum teres. Major qualifications for surgery included persistent hip pain despite conservative treatment and mechanical symptoms or instability symptoms (e.g., clicking or locking). Advanced arthritis (i.e., radiographic joint space < 2 mm) was the only reported contraindication. Patients were followed postoperatively for 1.5 to 60 months and were assessed using subjective methods (i.e., modified Harris Hip Score [mHHS] and Non-Arthritic Hip Score [NAHS]). Overall, both debridement and reconstruction improved the condition of patients, with a 40% increase in reported postoperative functional scores as well as a reported 89% of patients who were able to return to regular activity/sport. CONCLUSIONS: Ligamentum teres debridement is indicated for short-term relief of hip pain caused by partial-thickness tears (type 2) failing conservative management, whereas reconstruction with autografts, allografts, or synthetic grafts may be indicated for type 1 (full-thickness) ligamentum teres tears that are deemed "reparable," cause instability, have failed previous debridement, or a combination of these conditions. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV and Level V studies. PMID- 25125382 TI - Arthroscopy-assisted surgery for tibial plateau fractures. AB - PURPOSE: This study aimed to summarize the recent clinical outcomes of patients undergoing arthroscopy-assisted reduction and internal fixation (ARIF) for tibial plateau fractures. METHODS: A systematic electronic search of the PubMed and Cochrane databases was performed in January 2014. All English-language clinical studies on tibial plateau fractures treated with ARIF that were published after January 1, 2000 were eligible for inclusion. Basic information related to the surgery was collected. RESULTS: The search criteria initially identified 141 articles, and 19 studies were included in this systematic review. There were 2 retrospective comparative studies, 16 case series studies, and one clinical series based on a technique note. There were a total of 609 patients in this systematic review, with a mean follow-up time of 52.5 months. The most common fracture types were Schatzker types II and III. Concomitant injuries were common: 42.2% of the patients had meniscal injuries, and 21.3% had anterior cruciate ligament (ACL) injuries. In addition, the status of 90.5% of the patients was classified as good or excellent according to the clinical Rasmussen scoring system, and 90.9% of the patients were satisfied with the treatment. Only 6 severe complications were reported, including one case of compartment syndrome. CONCLUSIONS: ARIF is a reliable, effective, and safe method for the treatment of tibial plateau fractures, especially when they present with concomitant injuries. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and Level IV studies. PMID- 25125385 TI - Hydroxychloroquine's Efficacy as an Antiplatelet Agent Study in Healthy Volunteers: A Proof of Concept Study. AB - BACKGROUND: With the inflammatory model of atherosclerosis taking center stage, anti-inflammatory drugs hold a promising place in the therapy of cardiovascular disease (CVD). Recent studies showed that hydroxychloroquine (HCQ) was protective against thrombovascular events in lupus erythematosus and traditional cardiovascular risk factors in patients with rheumatoid arthritis. Some preliminary experimental data have shown that it may prevent platelet activation too. OBJECTIVE: To evaluate the antiplatelet activity of HCQ when given alone and in combination with aspirin (ASA) and compare it with ASA alone and ASA plus clopidogrel (CLOP) in healthy human volunteers. METHODS: In part 1 of the study, 8 volunteers were given HCQ for 7 days. In part 2, 12 volunteers were randomly assigned in a 1:1:1 ratio to the 3 groups in which 2 of the 3 treatments, ASA, ASA plus CLOP, and ASA plus HCQ, were given in the 2 treatment periods separated by a 14-day washout period using the incomplete block design. Inhibition of platelet aggregation (IPA) was measured by light transmission aggregometry. RESULTS: When arachidonic acid (AA) was used as agonist, HCQ given alone showed a significant reduction in platelet aggregation (11.0% +/- 4.2%, P = .03). The IPA was significantly increased when ASA plus HCQ was compared with ASA alone (31.2% +/- 8.1%, P = .002). This synergistic effect was not seen with adenosine diphosphate and collagen as agonists. Levels of serum 11-dehydrothromboxane B2, a stable marker of thromboxane A2 production, were not significantly different between the groups. There was also a significant decrease in fibrinogen and erythrocyte sedimentation rate values when HCQ was used alone or in combination with ASA. CONCLUSION: This study suggests that HCQ has antiplatelet properties possibly through the AA pathway (downstream to thromboxane A2 production). With possible additional beneficial effects over the traditional CVD risk factors, larger studies in the future might explore HCQ's potential as an antiplatelet agent. PMID- 25125383 TI - Detection of C3d-binding donor-specific anti-HLA antibodies at diagnosis of humoral rejection predicts renal graft loss. AB - Antibody-mediated rejection (AMR) is a major cause of kidney graft loss, yet assessment of individual risk at diagnosis is impeded by the lack of a reliable prognosis assay. Here, we tested whether the capacity of anti-HLA antibodies to bind complement components allows accurate risk stratification at the time of AMR diagnosis. Among 938 kidney transplant recipients for whom a graft biopsy was performed between 2004 and 2012 at the Lyon University Hospitals, 69 fulfilled the diagnosis criteria for AMR and were enrolled. Sera banked at the time of the biopsy were screened for the presence of donor-specific anti-HLA antibodies (DSAs) and their ability to bind C1q and C3d using flow bead assays. In contrast with C4d graft deposition, the presence of C3d-binding DSA was associated with a higher risk of graft loss (P<0.001). Despite similar trend, the difference did not reach significance with a C1q-binding assay (P=0.06). The prognostic value of a C3d-binding assay was further confirmed in an independent cohort of 39 patients with AMR (P=0.04). Patients with C3d-binding antibodies had worse eGFR and higher DSA mean fluorescence intensity. In a multivariate analysis, only eGFR <30 ml/min per 1.73 m(2) (hazard ratio [HR], 3.56; 95% confidence interval [CI], 1.46 to 8.70; P=0.005) and the presence of circulating C3d-binding DSA (HR, 2.80; 95% CI, 1.12 to 6.95; P=0.03) were independent predictors for allograft loss at AMR diagnosis. We conclude that assessment of the C3d-binding capacity of DSA at the time of AMR diagnosis allows for identification of patients at risk for allograft loss. PMID- 25125384 TI - Sex differences and attitudes toward living donor kidney transplantation among urban black patients on hemodialysis. AB - BACKGROUND AND OBJECTIVES: Living donor kidney transplantation, the treatment of choice for ESRD, is underused by women and blacks. To better understand sex differences in the context of potential barriers to living donor kidney transplantation, the Dialysis Patient Transplant Questionnaire was administered in two urban, predominantly black hemodialysis units. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Dialysis Patient Transplant Questionnaire was designed to study barriers to kidney transplantation from previously validated questions. Between July of 2008 and January of 2009, the Dialysis Patient Transplant Questionnaire was administered to 116 patients on hemodialysis, including potentially eligible and ineligible living donor kidney transplantation candidates. Of 101 patients who self-identified as black or African American, 50 (49.5%) patients had the questionnaire entirely administered by the researcher or assistant, 25 (24.8%) patients required some assistance, and 26 (25.7%) patients completed the Dialysis Patient Transplant Questionnaire entirely by themselves. Multiple logistic regression methods were used to determine if the observed bivariate associations and differences persisted when controlled for potential confounders. RESULTS: Women were less likely to want living donor kidney transplantation compared with men (58.5% versus 87.5%, P=0.003), despite being nearly two times as likely as men to receive unsolicited offers for kidney transplant (73.2% versus 43.2%, P=0.02). They were also less likely to have been evaluated for a kidney transplant (28.3% versus 52.2%, P=0.01). The multiple logistic regression analysis showed that sex was a statistically significant predictor of wanting living donor kidney transplantation (women versus men odds ratio, 0.13; 95% confidence interval, 0.04 to 0.46), controlling for various factors known to influence transplant decisions. A sensitivity analysis indicated that mode of administration did not bias these results. CONCLUSIONS: In contrast to previous studies, the study found that black women were less likely to want living donor kidney transplantation compared with black men. Black women were also less likely to be evaluated for a kidney transplant, although they were more likely to receive an unsolicited living donor kidney transplantation offer. PMID- 25125387 TI - East Kent trust is placed in special measures after being rated inadequate. PMID- 25125386 TI - Comparison of referrals for lumbar spine magnetic resonance imaging from physiotherapists, primary care and secondary care: how should referral pathways be optimised? AB - OBJECTIVE: To compare sensitivity of pathology on imaging between referrals from primary care, physiotherapists, spinal surgeons and other secondary care providers. DESIGN AND SETTING: A retrospective review of 200 consecutive magnetic resonance imaging (MRI) scans of patients' first presentations to radiology for MR lumbar scanning at a tertiary orthopaedic centre. A scan report was defined as positive if there was any evidence of neural compromise. Fisher's exact 2*2 contingency analyses were performed. RESULTS: Eighty-seven (44%) scans were positive and 113 (57%) were negative. Forty-four percent of scans requested by general practitioners (GPs) were reported as positive compared with 57% of scans requested by physiotherapists. Only 40% and 20% of scans requested by specialist spinal surgeons and non-spinal team secondary care providers were positive, respectively. Physiotherapist referrals for MRI lumbar spine scans were significantly more likely to be positive compared with GPs (P=0.05), spinal surgeons (P=0.03) and others (P=0.004). CONCLUSION: When appropriate, referrals via the extended physiotherapy service should be encouraged, rather than referrals directly from GPs. With appropriate training and in the appropriate clinical context, extended physiotherapy services could include inpatients and could accept outpatient referrals from other secondary care providers and not just from GPs; this would improve efficiency and reduce the workload of the radiology department and the spinal surgical unit. PMID- 25125388 TI - G-protein alphaq participates in the steroid hormone 20-hydroxyecdysone nongenomic signal transduction. AB - The nuclear receptor-mediated genomic pathways of the animal steroid hormones are well known. However, the cell membrane receptor-mediated nongenomic pathways of the animal steroid hormones are little understood. In this study, we report the participation of a G-protein alpha q (Galphaq)(1) subunit in the 20E nongenomic pathway in the cell membrane and regulating gene expression during molting and metamorphosis in a lepidopteran insect, Helicoverpa armigera. 20E-induced phosphorylation of Galphaq was detected using two-dimensional electrophoresis techniques. Knockdown of Galphaq by injecting double-stranded RNA suppressed the development of larvae, delayed metamorphosis, and inhibited 20E-induced gene expression. Galphaq was distributed throughout the cell, and migrated toward the plasma membrane upon 20E induction. Galphaq was necessary in the 20E-induced intracellular Ca(2+) release and extracellular Ca(2+) influx. The protein kinase C (PKC) inhibitor could repress 20E-induced phosphorylation of cyclin-dependent kinase 10 (CDK10) and transcription factor ultraspiracle (USP1). PKC inhibitor could repress the Galphaq phosphorylation and membrane trafficking. These results suggest that Galphaq participates in 20E signaling in the cell membrane at the pre-genomic stage by modulating the increase of the intracellular Ca(2+) and phosphorylation of CDK10 and USP1 in 20E transcription complex to regulate gene transcription. PMID- 25125389 TI - DHEA - a precursor of ERbeta ligands. AB - What is DHEA and why is there so much public interest in this steroid which has been touted as the fountain of youth and is supposed to have all kinds of health benefits? Endocrinologists have been fascinated with DHEA for a long time because of its high production in the fetal adrenals and its continued high levels until the 7th decade of life. Yet there is still little agreement about its physiological functions. In its simplest terms endocrinology is the communication between at least three organs: one sends a message, one releases a hormone into the blood in response to the message and one responds to the hormone. DHEA is produced by a specific zone of the adrenal cortex, the zona reticularis, whose sole function is to produce this steroid. Glucocorticoids and mineralocorticoids which are C21 steroids are produced in two other zones of the adrenal cortex called the zona fasicularis and the zona glomerulosa, respectively. Being C21 steroids, they cannot be synthesized from DHEA which is a C19 steroid. To date there is no known hormone which specifically stimulates the zona reticularis and there is no known specific receptor for DHEA. Thus DHEA does not qualify as a hormone. DHEA could have autocrine or paracrine effects but, so far, there is no known effect of DHEA on either the cells of the zona glomerulosa or the zona fasicularis. Of course DHEA could have functions as a local precursor of androgens or estrogens and many studies have reported on the beneficial effects of transdermal or transvaginal administration of DHEA in postmenopausal women. This review will consider two of the potential functions of DHEA as a precursor of estrogen receptor beta (ERbeta) ligands. PMID- 25125390 TI - Testosterone decreases fluid and chloride secretions in the uterus of adult female rats via down-regulating cystic fibrosis transmembrane regulator (CFTR) expression and functional activity. AB - OBJECTIVES: Estrogen is known to stimulate uterine fluid and Cl(-) secretion via CFTR. This study investigated testosterone effect on these changes in a rat model. METHODS: Ovariectomized adult female rats received estrogen for five days or estrogen for three days followed by two days peanut oil or testosterone either alone or in the presence of flutamide or finasteride. At the end of treatment, uteri were perfused with perfusate containing CFTRinh-172. The rate of fluid and Cl(-) secretion were determined. Dose-dependent effect of testosterone and effect of forskolin on fluid secretion rate were measured. Animals were sacrificed and uteri were removed for CFTR protein and mRNA expression analyses, histology and cAMP measurement. Morphology of uterus, levels of expression of CFTR protein and mRNA and distribution of CFTR protein were observed. RESULTS: Estrogen causes increase while testosterone causes decrease in uterine fluid and Cl(-) secretions. The effects of estrogen but not testosterone were antagonized by CFTRinh-172. Luminal fluid volume and apical expression of CFTR in the luminal epithelia were highest under estrogen and lowest under testosterone influences. Similar changes were observed in CFTR protein and mRNA expressions. Uterine cAMP level was highest under estrogen and lowest under testosterone influence. Forskolin increases fluid secretion rate in estrogen but not in testosterone treated animals. Testosterone effects were dose-dependent and were antagonized by flutamide however, not finasteride. CONCLUSIONS: Testosterone inhibition of estrogen-induced uterine fluid and Cl(-) secretion occurs via inhibition of CFTR expression and functional activities. These changes could explain the adverse effects of testosterone on fertility. PMID- 25125391 TI - Assessment of psychiatric disorders among sex offenders: Prevalence and associations with criminal history. AB - BACKGROUND: Much of the research on the prevalence of psychiatric disorders among sex offenders has been conducted in the USA or Europe. Less is known about it in other regions, particularly in Asia. AIMS: The objective of this study is to determine the prevalence of psychiatric disorders among sex offenders in Taiwan and their associations with offender characteristics and criminal history. METHODS: Participants were randomly selected from men serving sentences in Taiwan's prison for serious sex offenders. Consenting men were assessed using the structured clinical interviews for DSM-IV-TR Axis I and II disorders. Demographics and criminal history were also recorded. RESULTS: Over two-thirds of the 68 participants met criteria for one or more lifetime Axis I disorders, and nearly 60% met criteria for one or more Axis II disorder. The higher the number of Axis I and cluster B personality disorders, the higher was the total number of convictions. CONCLUSIONS: Our study adds to the literature that suggests that psychiatric assessment is likely to have an important role in the management and treatment of sex offenders. The finding that multiple disorders are common in this group and associated with more convictions for sex offences suggests that failure to include psychiatric assessment in planning the management of sex offenders may increase the risk of recidivism. PMID- 25125393 TI - Fertility-sparing management combined with photodynamic therapy for endometrial stromal sarcoma: a case report. AB - BACKGROUND AND OBJECTIVES: Low-grade endometrial sarcoma (LGESS) has a favorable prognosis after standard surgical treatment. The conservative fertility-sparing treatments in young patients with LGESS have been reported; however, the role of conservative therapy is not well defined. STUDY DESIGN/PATIENT AND METHODS: A 31 year-old nulliparous woman was diagnosed with LGESS after resection of a cervical polyp with resection margin positive for malignancy. She underwent fertility sparing surgery including laparoscopic pelvic lymph node dissection, hysteroscopic endometrial polypectomy, endocervical curettage, and photodynamic therapy (PDT) on the endometrium and uterine cervix. And she had received adjuvant therapy with a non-steroidal aromatase inhibitor. RESULTS: She conceived by in vitro fertilization and delivered twins at 32+2 weeks gestation by Cesarean section 32 months after conservative treatment. She has no evidence of recurrence after 99 months of follow-up. CONCLUSION: Conservative management of LGESS may be attempted in selected patients who want to preserve fertility. Conservative surgery combined with PDT has shown effective results in long-term follow-up. PMID- 25125392 TI - Cumulative dietary exposure to a selected group of pesticides of the triazole group in different European countries according to the EFSA guidance on probabilistic modelling. AB - The practicality was examined of performing a cumulative dietary exposure assessment according to the requirements of the EFSA guidance on probabilistic modelling. For this the acute and chronic cumulative exposure to triazole pesticides was estimated using national food consumption and monitoring data of eight European countries. Both the acute and chronic cumulative dietary exposures were calculated according to two model runs (optimistic and pessimistic) as recommended in the EFSA guidance. The exposures obtained with these model runs differed substantially for all countries, with the highest exposures obtained with the pessimistic model run. In this model run, animal commodities including cattle milk and different meat types, entered in the exposure calculations at the level of the maximum residue limit (MRL), contributed most to the exposure. We conclude that application of the optimistic model run on a routine basis for cumulative assessments is feasible. The pessimistic model run is laborious and the exposure results could be too far from reality. More experience with this approach is needed to stimulate the discussion of the feasibility of all the requirements, especially the inclusion of MRLs of animal commodities which seem to result in unrealistic conclusions regarding their contribution to the dietary exposure. PMID- 25125394 TI - The development of a high-throughput measurement method of octanol/water distribution coefficient based on hollow fiber membrane solvent microextraction technique. AB - This paper describes the development of a novel high-throughput hollow fiber membrane solvent microextraction technique for the simultaneous measurement of the octanol/water distribution coefficient (logD) for organic compounds such as drugs. The method is based on a designed system, which consists of a 96-well plate modified with 96 hollow fiber membrane tubes and a matching lid with 96 center holes and 96 side holes distributing in 96 grids. Each center hole was glued with a sealed on one end hollow fiber membrane tube, which is used to separate the aqueous phase from the octanol phase. A needle, such as microsyringe or automatic sampler, can be directly inserted into the membrane tube to deposit octanol as the accepted phase or take out the mixture of the octanol and the drug. Each side hole is filled with aqueous phase and could freely take in/out solvent as the donor phase from the outside of the hollow fiber membranes. The logD can be calculated by measuring the drug concentration in each phase after extraction equilibrium. After a comprehensive comparison, the polytetrafluoroethylene hollow fiber with the thickness of 210 MUm, an extraction time of 300 min, a temperature of 25 degrees C and atmospheric pressure without stirring are selected for the high throughput measurement. The correlation coefficient of the linear fit of the logD values of five drugs determined by our system to reference values is 0.9954, showed a nice accurate. The -8.9% intra-day and -4.4% inter-day precision of logD for metronidazole indicates a good precision. In addition, the logD values of eight drugs were simultaneously and successfully measured, which indicated that the 96 throughput measure method of logD value was accurate, precise, reliable and useful for high throughput screening. PMID- 25125395 TI - Simultaneous quantification of 5-hydroxyindoleacetic acid and 5-hydroxytryptamine by capillary electrophoresis with quantum dot and horseradish peroxidase enhanced chemiluminescence detection. AB - A capillary electrophoresis (CE) with chemiluminescence (CL) detection method was developed for the simultaneous quantification of 5-hydroxyindoleacetic acid (5 HIAA) and 5-hydroxytryptamine (5-HT). In this method, CdTe quantum dot (QD) and horseradish peroxidase (HRP) were used as enhancing reagents to co-catalyze the post-column CL reaction between luminol and hydrogen peroxide, achieving highly efficient CL emission. 5-HIAA and 5-HT inhibit the CL emission resulting to the formation of negative peaks in electropherogram. The degree of CL suppression is proportional to the concentration of 5-HT and 5-HIAA. The linear ranges for the determination of 5-HIAA and 5-HT were 2.5*10(-8)-2.5*10(-6) M and 2.5*10(-8) 5.0*10(-6) M with detection limits (signal/noise=3) of 7.0*10(-9) M and 6.0*10( 9) M, respectively. Intraday precision do not exceed 5.0%. The accuracy was confirmed by the recoveries ranged from 98% to 104%. The present method was successfully applied for the quantification of 5-HIAA and 5-HT in human urine. The concentrations of 5-HT and 5-HIAA in human urine were found to be in the range of 0.78-1.2 MUM and 3.2-5.1 MUM, respectively. PMID- 25125396 TI - Overestimation of 25-hydroxyvitamin D3 by increased ionisation efficiency of 3 epi-25-hydroxyvitamin D3 in LC-MS/MS methods not separating both metabolites as determined by an LC-MS/MS method for separate quantification of 25-hydroxyvitamin D3, 3-epi-25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum. AB - BACKGROUND: An LC-MS/MS method was developed for simultaneous quantification of 25-hydroxyvitamin D3 (25(OH)D3), 3-epi-25(OH)D3, and 25(OH)D2 in human serum. METHODS: Sample preparation consisted of protein precipitation followed by off line SPE. Calibration curves for each vitamin D metabolite were constructed in phosphate-buffered saline with 60 g/L albumin including its corresponding stable isotope labelled (SIL) internal standard. A pentafluorophenyl (PFP) analytical column was used to resolve 25(OH)D3 from 25(OH)D2 and 3-epi-25(OH)D3, followed by SRM registration using positive ESI-MS/MS. Accuracy was assessed from measurement of samples with NIST reference method procedure (RMP) assigned values. The PFP LC MS/MS method was compared to an in-house C18 column LC-MS/MS method, not resolving 25(OH)D3 from 3-epi-25(OH)D3, using adult and newborn samples. RESULTS: Intra-assay and inter-assay coefficients of variation were less than 4% and 7.5%, respectively for all three vitamin D metabolites; lower limits of quantification were 1, 1 and 2 nmol/L and linearity of methods were 1-500, 1-200 and 2-500 nmol/L for 25(OH)D3, 3-epi-25(OH)D3 and 25(OH)D2, respectively. The PFP LC-MS/MS method showed minimal bias to the NIST RMP. Method comparison revealed that in the C18 LC-MS/MS method, the 3-epi-25(OH)D3 concentration is overestimated inadvertently not only from co-elution of both analytes, but also by an additional 30-40% higher ionisation efficiency of 3-epi-25(OH)D3 when compared to 25(OH)D3. CONCLUSION: This accurate LC-MS/MS method allows the simultaneous measurement of 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 in human serum. Due to increased ionisation efficiency, the contribution of the 3-epi-25(OH)D3 metabolite to the total 25(OH)D3 concentration is significantly overestimated in MS methods that do not resolve 3-epi-25(OH)D3 from 25(OH)D3 and may compromise its use in infant samples known to have significant amounts of 3-epi-25(OH)D3. PMID- 25125397 TI - Performance characterization of a quantitative liquid chromatography-tandem mass spectrometric method for 12 macrolide and lincosamide antibiotics in salmon, shrimp and tilapia. AB - This paper describes an extension and performance characterization of a quantitative confirmatory multi-residue liquid chromatography-tandem mass spectrometric method for residues of macrolide and lincosamide antibiotics, originally validated for application to bovine kidney tissues, to tissues of salmon, shrimp and tilapia. The 12 analytes include clindamycin, erythromycin A, gamithromycin, josamycin, lincomycin, neospiramycin 1, oleandomycin, pirlimycin, spiramycin 1, tildipirosin, tilmicosin and tylosin A. The limit of detection was 0.5 MUg/kg. Within-laboratory precision evaluated over the analytical range of 5.0-50.0 MUg/kg ranged from 4 to 17%. The accuracy of the method ranged from 80 to 112%. Recoveries ranged from 47 to 99% with all but one recovery above 60%. This is the first report of a quantitative confirmatory method for gamithromycin, pirlimycin and tildipirosin in fish and shrimp. PMID- 25125398 TI - Development of an LC-MS/MS method for high throughput quantification of metformin uptake in transporter inhibition assays. AB - A high throughput LC-MS/MS method for quantification of metformin substrate uptake enables conversion of radiometric transporter inhibition assays for multidrug and toxin extrusion transporters (MATE 1 and 2) and organic cation transporter 2 (OCT2) to a nonradioactive format. Such conversion greatly simplifies assay complexity and reduces assay costs. The development of a quantitative LC-MS/MS method for metformin in support of the high throughput transporter inhibition assays faced specific challenges of achieving both adequate chromatographic retention and rapid analytical turnaround. Here we report a method that circumvents both challenges. The utilization of a porous graphitic carbon column (Hypercarb) ensured adequate retention of highly polar metformin in biological samples. The combined employment of a ballistic gradient on a 3 mm * 30 mm, 5 MUm Hypercarb column, and dual staggered chromatography coupled with multiple injection chromatography acquisition, yielded a fast injection-to-injection cycle time of 30s. The method demonstrated good accuracy, precision and excellent robustness for high throughput applications, and has been successfully implemented in the development and validation of the nonradioactive transporter inhibition assays for MATEs and OCT2. PMID- 25125400 TI - Treat sickest hepatitis C patients first, new US guidelines recommend. PMID- 25125402 TI - Combined animal and plant health agency to be created. PMID- 25125401 TI - EFSA assesses the impact of scrapie eradication policies. PMID- 25125403 TI - FSA releases first results from Campylobacter survey. PMID- 25125404 TI - Bristol academic recognised for contributions to feline medicine. PMID- 25125405 TI - Celebrating success in statutory membership exam. PMID- 25125406 TI - BVA steps up non-stun slaughter campaign. PMID- 25125399 TI - Cargo sorting in the endocytic pathway: a key regulator of cell polarity and tissue dynamics. AB - The establishment and maintenance of polarized plasma membrane domains is essential for cellular function and proper development of organisms. Epithelial cells polarize along two fundamental axes, the apicobasal and the planar, both depending on finely regulated protein trafficking mechanisms. Newly synthesized proteins destined for either surface domain are processed along the biosynthetic pathway and segregated into distinct subsets of transport carriers emanating from the trans-Golgi network or endosomes. This exocytic trafficking has been identified as essential for proper epithelial polarization. Accumulating evidence now reveals that endocytosis and endocytic recycling play an equally important role in epithelial polarization and the appropriate localization of key polarity proteins. Here, we review recent work in metazoan systems illuminating the connections between endocytosis, postendocytic trafficking, and cell polarity, both apicobasal and planar, in the formation of differentiated epithelial cells, and how these processes regulate tissue dynamics. PMID- 25125407 TI - New partnership a first for the AWF. PMID- 25125408 TI - Views sought on global standard for animal welfare in vet schools. PMID- 25125409 TI - Private Members Bill proposes regulation of commercial cat breeding. PMID- 25125410 TI - WSAVA advises on companion animal vaccination in Asia. PMID- 25125411 TI - Helping farmers choose the best livestock for tropical climates. PMID- 25125412 TI - FVE seeks views on recommendations for improving aquatic animal health. PMID- 25125413 TI - 'Tour de Yorkshire' raises funds for Indian animal welfare charity. PMID- 25125414 TI - MERS infection in animals to be reported as an emerging disease. PMID- 25125415 TI - Responding to concerns about complaints. AB - When the RCVS asked members of the profession and public about its complaints and disciplinary system, it received a great deal of feedback - some positive, but much of it critical. Here, Luke Bishop, RCVS communications officer, describes how the process has now been overhauled with the aim of making it quicker, more efficient and a more satisfactory experience for all involved. PMID- 25125416 TI - Unusual cases of blackleg in cattle. PMID- 25125417 TI - Impact of Schmallenberg virus on British farms. PMID- 25125418 TI - Angiostrongylus vasorum infection in Cornwall. PMID- 25125419 TI - PDSA to expand its charitable objects. PMID- 25125420 TI - Fungal ingestion in companion animals. PMID- 25125421 TI - A validation study of the Hong Kong version of Montreal Cognitive Assessment (HK MoCA) in Chinese older adults in Hong Kong. AB - OBJECTIVE: To validate the Hong Kong version of Montreal Cognitive Assessment (HK MoCA) in identification of mild cognitive impairment and dementia in Chinese older adults. DESIGN: Cross-sectional study. SETTING: Cognition clinic and memory clinic of a public hospital in Hong Kong. PARTICIPANTS: A total of 272 participants (dementia, n=130; mild cognitive impairment, n=93; normal controls, n=49) aged 60 years or above were assessed using HK-MoCA. The HK-MoCA scores were validated against expert diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed) criteria for dementia and Petersen's criteria for mild cognitive impairment. Statistical analysis was performed using receiver operating characteristic curve and regression analyses. Additionally, comparison was made with the Cantonese version of Mini-Mental State Examination and Global Deterioration Scale. RESULTS: The optimal cutoff score for the HK-MoCA to differentiate cognitive impaired persons (mild cognitive impairment and dementia) from normal controls was 21/22 after adjustment of education level, giving a sensitivity of 0.928, specificity of 0.735, and area under the curve of 0.920. Moreover, the cutoff to detect mild cognitive impairment was 21/22 with a sensitivity of 0.828, specificity of 0.735, and area under the curve of 0.847. Score of the Cantonese version of the Mini-Mental State Examination to detect mild cognitive impairment was 26/27 with a sensitivity of 0.785, specificity of 0.816, and area under the curve of 0.857. At the optimal cutoff of 18/19, HK-MoCA identified dementia from controls with a sensitivity of 0.923, specificity of 0.918, and area under the curve of 0.971. CONCLUSION: The HK-MoCA is a useful cognitive screening instrument for use in Chinese older adults in Hong Kong. A score of less than 22 should prompt further diagnostic assessment. It has comparable sensitivity with the Cantonese version of Mini-Mental State Examination for detection of mild cognitive impairment. It is brief and feasible to conduct in the clinical setting, and can be completed in less than 15 minutes. Thus, HK-MoCA provides an attractive alternative screening instrument to Mini Mental State Examination which has ceiling effect (ie may fail to detect mild/moderate cognitive impairment in people with high education level or premorbid intelligence) and needs to be purchased due to copyright issues. PMID- 25125422 TI - Investigation of availability and accessibility of community automated external defibrillators in a territory in Hong Kong. AB - OBJECTIVE: To evaluate the availability and accessibility of community automated external defibrillators in a territory in Hong Kong. DESIGN: Cross-sectional study. SETTING: Two public hospitals in New Territories West Cluster in Hong Kong. PARTICIPANTS: Information about the locations of community automated external defibrillators was obtained from automated external defibrillator suppliers and through community search. Data on locations of out-of-hospital cardiac arrests from August 2010 to September 2013 were obtained from the local cardiac arrest registry of the emergency departments of two hospitals. Sites of both automated external defibrillators and out-of-hospital cardiac arrests were geographically coded and mapped. The number of out-of-hospital cardiac arrests within 100 m of automated external defibrillators per year and the proportion of out-of-hospital cardiac arrests with accessible automated external defibrillators (100 m) were calculated. The number of community automated external defibrillators per 10,000 population and public access defibrillation rate were also calculated and compared with those in other countries. RESULTS: There were a total of 207 community automated external defibrillators in the territory. The number of automated external defibrillators per 10,000 population was 1.942. All facilities with automated external defibrillators in this territory had more than 0.2 out-of-hospital cardiac arrests per automated external defibrillator per year within 100 m. Among all out-of-hospital cardiac arrests, 25.2% could have an automated external defibrillator reachable within 100 m. The public access defibrillation rate was 0.168%. CONCLUSIONS: The number and accessibility of community automated external defibrillators in this territory are comparable to those in other developed countries. The placement site of community automated external defibrillators is cost-effective. However, the public access defibrillation rate is low. PMID- 25125423 TI - Clinical applications of age-related macular degeneration genetics. AB - Understanding genetic causes of age-related macular degeneration (AMD) will eventually yield effective discoveries and improvements in predictive/prognostic methods. These include, but are not limited to, reliable disease prediction (screening for increased discrimination of clinical risk), differential classification of AMD subtypes with biomarkers (development of risk-linked molecular taxonomies), selection of optimal preventive and therapeutic interventions (guided by a biologically meaningful understanding of treatment response), and drug dosing. In this review, we discuss clinical applications informed by key findings in AMD genetics, and provide commentary on leveraging extant and forthcoming evidence to improve AMD risk prediction, AMD classification, and knowledge on the genetic basis of drug activity and toxicity. Advances in translating AMD genetics findings for AMD risk prediction require development of a genetics-based causality for AMD incidence and progression. Molecular subtyping of AMD phenotypes requires a set of dynamic biomarkers presenting prognostic value; although these have yet to be identified, the formation of multidisciplinary teams and their participation in large-scale consortia may yield promising results. Drugs targeting complement and vascular endothelial growth factor (VEGF) systems are under evaluation, and forthcoming work on rare variants and noncoding DNA in AMD pathogenesis will likely reveal biochemical pathways enriched with AMD-associated genetic variants. Pharmacologic targets in these pathways may inform a rational and effective therapeutic approach to preventing and treating this sight-threatening disease. PMID- 25125426 TI - Early experience affects the strength of vigilance for threat in rhesus monkey infants. AB - Both human and nonhuman primates exhibit a cognitive bias to social threat, but little is known about how this bias develops. We investigated the development of threat bias in free-ranging infant rhesus macaques (Macaca mulatta) at 3 months (n = 45) and 9 months (n = 46) of age. Three-month-olds did not display bias, but 9-month-olds exhibited increased maintenance of attention to threatening social stimuli. To examine whether the social environment affected this increased vigilance for threat, we collected behavioral data on maternal rank and protectiveness across the first 12 weeks of life for infants tested at 9 months. Among 9-month-olds, those of high-ranking and more protective mothers displayed greater vigilance for threat than those of lower-ranking and less protective mothers. These results demonstrate that infant social cognition is shaped by mothers both directly (via protectiveness) and indirectly (through social rank). PMID- 25125427 TI - Gaze following is accelerated in healthy preterm infants. AB - Gaze following is an essential human communication cue that orients the attention of two interacting people to the same external object. This capability is robustly observed after 7 months of age in full-term infants. Do healthy preterm infants benefit from their early exposure to face-to-face interactions with other humans to acquire this capacity sooner than full-term infants of the same chronological age, despite their immature brains? In two different experiments, we demonstrated that 7-month-old preterm infants performed like 7-month-old full term infants (with whom they shared the same chronological age) and not like 4 month-old full-term infants (with whom they shared the same postmenstrual age). The duration of exposure to visual experience thus appears to have a greater impact on the development of early gaze following than does postmenstrual age. PMID- 25125424 TI - Lower urinary tract symptoms in men. AB - Benign prostatic hyperplasia (BPH) is a highly prevalent and costly condition that affects older men worldwide. Many affected men develop lower urinary tract symptoms, which can have a negative impact on their quality of life. In the past, transurethral resection of the prostate (TURP) was the mainstay of treatment. However, several efficacious drug treatments have been developed, which have transformed BPH from an acute surgical entity to a chronic medical condition. Specifically, multiple clinical trials have shown that alpha adrenoceptor antagonists can significantly ameliorate lower urinary tract symptoms. Moreover, 5alpha reductase inhibitors, alone or combined with an alpha adrenoceptor antagonist, can reverse the natural course of BPH, reducing the risk of urinary retention and the need for surgical intervention. Newer medical regimens including the use of antimuscarinic agents or phosphodiesterase type 5 inhibitors, have shown promise in men with predominantly storage symptoms and concomitant erectile dysfunction, respectively. For men who do not adequately respond to conservative measures or pharmacotherapy, minimally invasive surgical techniques (such as transurethral needle ablation, microwave thermotherapy, and prostatic urethral lift) may be of benefit, although they lack the durability of TURP. A variety of laser procedures have also been introduced, whose improved hemostatic properties abrogate many of the complications associated with traditional surgery. PMID- 25125429 TI - [We can do better to prevent head injuries]. PMID- 25125428 TI - Perceiving crowd attention: ensemble perception of a crowd's gaze. AB - In nearly every interpersonal encounter, people readily gather socio-visual cues to guide their behavior. Intriguingly, social information is most effective in directing behavior when it is perceived in crowds. For example, the shared gaze of a crowd is more likely to direct attention than is a single person's gaze. Are people equipped with mechanisms to perceive a crowd's gaze as an ensemble? Here, we provide the first evidence that the visual system extracts a summary representation of a crowd's attention; observers rapidly pooled information from multiple crowd members to perceive the direction of a group's collective gaze. This pooling occurred in high-level stages of visual processing, with gaze perceived as a global-level combination of information from head and pupil rotation. These findings reveal an important and efficient mechanism for assessing crowd gaze, which could underlie the ability to perceive group intentions, orchestrate joint attention, and guide behavior. PMID- 25125430 TI - [Research at Landspitali University Hospital - comparison with the Nordic countries and new opportunities]. PMID- 25125431 TI - [Visits to an emergency department due to head injuries]. AB - INTRODUCTION: Head injury is a common consequence of accidents and violence. It can result in permanent disability and is one of the leading causes of premature death worldwide. Our aim was to review all visits to Landspitali University Hospital (LUH) from head injuries, to study the incidence, nature and severity of head injuries. MATERIAL AND METHODS: A retrospective study on all visits of Reykjavik's inhabitants to LUH for head injuries in the years 2000-2005 and 2008 2009. Data were collected from patient records at LUH. One main diagnosis was used if head injury diagnoses were many. They were categorised into 5 groups; soft tissue injury, eye injury, injury to cranium, intracranial- and cranial nerve injury and multiple trauma. RESULTS: During the study period 35.031 patients presented with head injuries to LUH. Males were 67%. Mean age was 26 years (0-107). The highest rate was among infants and children aged 0-4 years (20.8%), followed by 5-9 years (11,5%) and 20-24 years (9.4%). The annual incidence decreased between the study periods from 4.2% to 3.3%. The annual incidence for admitted head injury patients decreased from 181/year/100.000 inhabitants to 110/year/100.000 inhabitants. Most often injuries were caused by accidents (80,5%) and violence (12.7%). Soft tissue injury was the most common injury (65%), followed by eye injury (15%) and intracranial- and cranial nerve injury (14%). The injuries that most frequently led to hospital admission were intracranial bleeding (90.1%), followed by skull fracture (79.2%). CONCLUSION: Accidents and violence caused most head injuries and they are more common among men than women. Patients with intracranial haemorrhage were usually admitted. Incidence of hospital visits and admissions because of head injuries in Reykjavik has decreased over the last decade. Key words: Head injury, accident, violence, brain injury, intracranial bleeding. PMID- 25125432 TI - [Giant thymoma - case report]. AB - Thymomas are usually benign tumors and are most often found in the anterior mediastinum. We report a rare case of a giant tumor in the right hemithorax that originated in the thymus. The tumor was 15x8 cm and histology revealed a type AB thymoma. The tumor was removed and the patient is doing well and is without symptoms two years after the operation. Key words: Thymoma, abdominal pain, giant tumor, mediastinum. PMID- 25125433 TI - [We are only human - reflection on nurse prosecution]. PMID- 25125434 TI - ["Shame and blame" threatens patient safety]. PMID- 25125435 TI - [Needle exchange programs are a cost-effective preventative measure against HIV in Iceland]. AB - OBJECTIVE: In 2007 there was a sudden increase in HIV cases among intravenous drug users (IDUs) in Iceland. In 2007 - 2011 there were 34 new HIV cases among IDUs compared to four in the previous four year period. The purpose of this study was to assess whether needle exchange programs (NEPs) were cost-effective in preventing the spread of HIV among IDUs in Iceland. MATERIALS AND METHODS: Cost utility analysis was conducted from a societal perspective. Costs are presented at the 2011 price level and values were discounted using a 3% discount rate. A ten year period, 2011 - 2020 was compared with and without NEPs. The Incremental Cost-Utility Ratio (ICUR) was calculated as societal cost per quality adjusted life year (QALY). Sensitivity analysis was performed on study assumptions. RESULTS: The estimated societal costs associated with HIV infections among IDUs from 2011 - 2020 was 914.369.621 ISK without NEP and 947.653.758 ISK with NEP. Excess societal cost due to NEP was 33.284.137 ISK. Societal utility from NEP was 7,39 QALYs. Additionally, NEP prevented 4-5 HIV infections. The ICUR of providing NEP was 4.506.720 ISK. CONCLUSION: According to WHO an intervention is considered cost-effective if the ICUR is less than three-fold national GDP per capita. In 2011 the GDP per capita in Iceland was 15.315.000 ISK. Sensitivity analysis on study assumptions yielded a societal cost within the WHO limit. Therefore, the results indicate that NEPs are cost-effective in preventing the spread of HIV among IDUs in Iceland. PMID- 25125436 TI - [Patient satisfaction with care and interaction with staff in the Acute Cardiac Unit at Landspitali - The National University Hospital of Iceland]. AB - INTRODUCTION: The Icelandic health care system ranks favourably in international comparison but patients' experience of interaction with the health service has not been well studied. The goal of this study was to examine the satisfaction of patients admitted to the Acute Cardiac Unit (ACU) at Landspitali - The National University Hospital of Iceland. METHODS: A questionnaire based on the Patient Satisfaction Questionnaire III was mailed to patients admitted to the ACU between 1 January and 29 February 2012. Questions were presented as statements and participants asked to respond how strongly on a scale from 1 to 5 they agreed or disagreed with each statement. Data analysis was performed using descriptive statistics, Cronbach's alpha for internal consistency of scales and principal components analysis, Wilcoxon-Mann-Whitney and Kruskal-Wallis tests for comparison of groups and Pearson and Spearman correlation coefficients for correlation between variables. RESULTS: The questionnaire was mailed to 485 individuals of whom 275 (57%) responded. The median age of the participants was 62 (range, 19-95) years and 132 (48%) were women. Internal consistency of the scales was mostly high (Cronbach's alpha 0.62-0.91) and principal components analysis revealed one main factor. The mean score of the questionnaire was 6.8 +/ 1.0 and 91%, and 86% of the participants were pleased with their interaction with physicians and nurses, respectively. Similarly, 88% were pleased with the care they recieved but 25% felt they received insufficient explanations of their symptoms or that follow-up care was lacking. CONCLUSION: Patients of the ACU generally appear to be satisfied with their care. However, our results suggest that improvement is needed in several areas, including information provided at discharge and follow-up care. PMID- 25125437 TI - [Cerebral ischemia/infarction - diagnosis and treatment]. AB - Four hundred individuals suffer from ischemic stroke every year in Iceland, more than one daily. Cerebral ischemia is an emergency. Around two million brain cells die every minute after an occlusion of a cerebral artery. Therefore, it is of utmost importance that the patient is transported quickly to hospital, not least to receive thrombolytic treatment. Even though thrombolytic treatment can be given up to four and a half hours after the ictal event, time is brain and the effect of thombolysis reduces dramatically as times passes. For every two patients who are treated inside one hour, one recovers fully. When the treatment is administred between three and four and a half hours only one in 14 recovers fully. All patients with an acute stroke should be admitted to a stroke unit where a multidisciplinary focus on stroke causation and treatment is present, with emphasis on early rehabilitation. Secondary preventive treatment focusing on anti-thrombotic, hypertensive, diabetic, cholesterol lowering treatment, carotic endarterectomy and life style changes should be initiated as soon as possible. PMID- 25125438 TI - Use patient power to tackle medical corruption in India. PMID- 25125439 TI - A prospective interrupted time series study of interventions to improve the quality, rating, framing and structure of goal-setting in community-based brain injury rehabilitation. AB - OBJECTIVE: To investigate whether the introduction of an electronic goals system followed by staff training improved the quality, rating, framing and structure of goals written by a community-based brain injury rehabilitation team. DESIGN: Interrupted time series design. INTERVENTION: Two interventions were introduced six months apart. The first intervention comprised the introduction of an electronic goals system. The second intervention comprised a staff goal training workshop. METHODS: An audit protocol was devised to evaluate the goals. A random selection of goal statements from the 12 months prior to the interventions (Time 1 baseline) were compared with all goal statements written after the introduction of the electronic goals system (Time 2) and staff training (Time 3). All goals were de-identified for client and time-period, and randomly ordered. RESULTS: A total of 745 goals (Time 1 n = 242; Time 2 n = 283; Time 3 n = 220) were evaluated. Compared with baseline, the introduction of the electronic goals system alone significantly increased goal rating, framing and structure (chi(2) tests 144.7, 18.9, 48.1, respectively, p < 0.001). The addition of staff training meant that the improvement in goal quality, which was only a trend at Time 2, was statistically significant at Time 3 (chi(2) 15.0, p <= 001). The training also led to a further significant increase in the framing and structuring of goals over the electronic goals system (chi(2) 11.5, 12.5, respectively, p <= 0.001). CONCLUSION: An electronic goals system combined with staff training improved the quality, rating, framing and structure of goal statements. PMID- 25125440 TI - Effectiveness of constraint-induced movement therapy on upper-extremity function in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials. AB - OBJECTIVE: To systematically examine the research literature on the effectiveness of constraint-induced movement therapy on improving arm function in children with cerebral palsy, and to assess the association between the study effect size and the characteristics of the patients and intervention protocol. DATA SOURCES: A systematic literature search was conducted in PubMed, PsycINFO, Cochrane, CINAHL, Web of Science, and TRIP Database up to May 2014. REVIEW METHODS: Studies employing randomized controlled trial design, children with cerebral palsy, comparing constraint-induced movement therapy with another intervention with a focus on arm function, and upper-extremity measures were included in this review. Methodological quality was evaluated using the Physiotherapy Evidence-based Database (PEDro) scale. RESULTS: The literature search resulted in 27 randomized controlled trial studies with good methodological quality that compared constraint-induced movement therapy with other intervention therapy. Overall, constraint-induced movement therapy provided a medium beneficial effect (d = 0.546; p < 0.001) when compared with conventional therapy. For the subgroup analyses, presence of a dose-equivalent comparison group, intervention location, and time of follow-up were significant factors. Studies examining constraint induced movement therapy effect without a dose-equivalent comparison group showed a large effect in children with cerebral palsy, but studies with a dose equivalent group only showed a small effect. Children who received home-based constraint-induced movement therapy had a better improvement in arm function than those who received constraint-induced movement therapy elsewhere. CONCLUSION: The research literature supports constraint-induced movement therapy as an effective intervention to improve arm function in children with cerebral palsy. PMID- 25125441 TI - Efficacy of electrical stimulation as an adjunct to repetitive task practice therapy on skilled hand performance in hemiparetic stroke patients: a randomized controlled trial. AB - OBJECTIVE: To assess the effects of additional electrical stimulation to hand muscles combined with repetitive task practice therapy on skilled hand performance in stroke patients. DESIGN: A randomized controlled study. SETTING: Neurological physical therapy outpatient clinic. SUBJECTS: Forty stroke patients of both sexes (45-65 years - 16 females and 24 males). METHODS: Participants were randomly assigned into two equal groups: experimental and control groups. All patients received repetitive task practice. Those in the experimental group received additional electrical stimulation for specific hand muscles and patients in the control group received sham electrical stimulation. Treatment was provided three times/week for two months. MAIN OUTCOME MEASURES: Patients received baseline and post-treatment assessments using three-dimensional motion analysis (to evaluate range of motion of fingers abduction and extension), motor assessment scale (to assess hand motor function) and time to complete Jebsen Taylor Test (to assess hand skills). RESULTS: Patients in the experimental group showed a significant improvement as compared with those in the control group. Motor assessment scale score was 4.25+/-0.63 for the experimental group and 3.35+/-0.74 for the control group (t=-3.50 and p= 0.0001). Time to complete Jebsen Taylor Test was 180.90+/-7.04 for the experimental group and 192.80+/-6.87 for the control group (t=4.50 and p= 0.0001). There was a significant improvement in fingers abduction and extension in both groups (in favor to the experimental group). CONCLUSION: Repetitive task practice therapy combined with electrical stimulation can improve skilled hand performance in terms of hand motor function, skills and range of motion in stroke patients. PMID- 25125442 TI - Participant and caregiver experience of the Nintendo Wii SportsTM after stroke: qualitative study of the trial of WiiTM in stroke (TWIST). AB - OBJECTIVE: To understand stroke survivors and their caregivers' experience and acceptability of using the Nintendo Wii SportsTM games (WiiTM) as a home-based arm rehabilitation tool. DESIGN: A qualitative study within a randomized controlled trial investigating the effectiveness of using the WiiTM for arm rehabilitation. Data were analysed using thematic analysis. SETTINGS: Participants and carers were interviewed in their homes. SUBJECTS: Eleven male and seven female participants and 10 caregivers who were taking part in the randomized controlled trial within six months of stroke. Median age 65. INTERVENTION: All participants were using the WiiTM for arm rehabilitation. MAIN MEASURES: Semi-structured interviews. RESULTS: Five themes were identified: diligence of play, perceived effectiveness, acceptability, caregiver and social support, and the set-up and administration of the WiiTM. Participants appreciated the ability to maintain a social role and manage other comorbidities around the use of the WiiTM. A small number of participants found the Mii characters too childlike for adult rehabilitation. The most popular game to start the rehabilitation programme was bowling. As confidence grew, tennis was the most popular, with baseball and boxing being the least popular games. Caregivers provided some practical support and encouragement to play the WiiTM. CONCLUSIONS: The WiiTM may provide an engaging and flexible form of rehabilitation with relatively high reported usage rates in a home setting. The WiiTM was acceptable to this sample of patients and their caregivers in home-based rehabilitation of the arm following stroke. PMID- 25125444 TI - LeishMicrosatDB: open source database of repeat sequences detected in six fully sequenced Leishmania genomes. AB - A Leishmania Microsatellite Database (LeishMicrosatDB) is reported for genome wise mining of microsatellites in six Leishmania species, using in silico techniques. This was created to provide parasitologists a platform to understand the genome characterization, mapping, phylogeny and evolutionary analysis. The present version of the database contains 1,738,669 simple sequence repeats of which 181 s756 repeats are present in compound form. The repeats can be sought in a chromosome using input parameters such as repeat type (mono- hexa), coding status, repeat unit length and repeat sequence motif. The genic repeats have been further hyperlinked with their corresponding locus id, and the database is appended with primer3 plus for primer designing of selected repeats with left and right flanking sequences up to 250 bp. Information on clustering and polymorphic repeats can also be retrieved. This database may also be adopted as a tool to study the relative occurrence and distribution of microsatellites across the parasitic genome. The database can enable a biologist to select markers at desired intervals over the chromosomes, and can be accessed as an open source repository at http://biomedinformri.com/leishmicrosat. DATABASE URL: http://biomedinformri.com/leishmicrosat. PMID- 25125443 TI - Mechanically-compliant intracortical implants reduce the neuroinflammatory response. AB - OBJECTIVE: The mechanisms underlying intracortical microelectrode encapsulation and failure are not well understood. A leading hypothesis implicates the role of the mechanical mismatch between rigid implant materials and the much softer brain tissue. Previous work has established the benefits of compliant materials on reducing early neuroinflammatory events. However, recent studies established late onset of a disease-like neurodegenerative state. APPROACH: In this study, we implanted mechanically-adaptive materials, which are initially rigid but become compliant after implantation, to investigate the long-term chronic neuroinflammatory response to compliant intracortical microelectrodes. MAIN RESULTS: Three days after implantation, during the acute healing phase of the response, the tissue response to the compliant implants was statistically similar to that of chemically matched stiff implants with much higher rigidity. However, at two, eight, and sixteen weeks post-implantation in the rat cortex, the compliant implants demonstrated a significantly reduced neuroinflammatory response when compared to stiff reference materials. Chronically implanted compliant materials also exhibited a more stable blood-brain barrier than the stiff reference materials. SIGNIFICANCE: Overall, the data show strikingly that mechanically-compliant intracortical implants can reduce the neuroinflammatory response in comparison to stiffer systems. PMID- 25125446 TI - A brain-computer interface based on self-regulation of gamma-oscillations in the superior parietal cortex. AB - OBJECTIVE: Brain-computer interface (BCI) systems are often based on motor- and/or sensory processes that are known to be impaired in late stages of amyotrophic lateral sclerosis (ALS). We propose a novel BCI designed for patients in late stages of ALS that only requires high-level cognitive processes to transmit information from the user to the BCI. APPROACH: We trained subjects via EEG-based neurofeedback to self-regulate the amplitude of gamma-oscillations in the superior parietal cortex (SPC). We argue that parietal gamma-oscillations are likely to be associated with high-level attentional processes, thereby providing a communication channel that does not rely on the integrity of sensory- and/or motor-pathways impaired in late stages of ALS. MAIN RESULTS: Healthy subjects quickly learned to self-regulate gamma-power in the SPC by alternating between states of focused attention and relaxed wakefulness, resulting in an average decoding accuracy of 70.2%. One locked-in ALS patient (ALS-FRS-R score of zero) achieved an average decoding accuracy significantly above chance-level though insufficient for communication (55.8%). SIGNIFICANCE: Self-regulation of gamma power in the SPC is a feasible paradigm for brain-computer interfacing and may be preserved in late stages of ALS. This provides a novel approach to testing whether completely locked-in ALS patients retain the capacity for goal-directed thinking. PMID- 25125445 TI - PlantCAZyme: a database for plant carbohydrate-active enzymes. AB - PlantCAZyme is a database built upon dbCAN (database for automated carbohydrate active enzyme annotation), aiming to provide pre-computed sequence and annotation data of carbohydrate active enzymes (CAZymes) to plant carbohydrate and bioenergy research communities. The current version contains data of 43,790 CAZymes of 159 protein families from 35 plants (including angiosperms, gymnosperms, lycophyte and bryophyte mosses) and chlorophyte algae with fully sequenced genomes. Useful features of the database include: (i) a BLAST server and a HMMER server that allow users to search against our pre-computed sequence data for annotation purpose, (ii) a download page to allow batch downloading data of a specific CAZyme family or species and (iii) protein browse pages to provide an easy access to the most comprehensive sequence and annotation data. DATABASE URL: http://cys.bios.niu.edu/plantcazyme/ PMID- 25125447 TI - Clinical research: the future of the molecular imaging technologist-a white paper presented by members of the graduate stakeholders committee of the SNMMI technologist section. PMID- 25125448 TI - Detection of Aberrant Right Subclavian Artery by PET/CT. AB - An aberrant right subclavian artery can be diagnosed by PET/CT, as demonstrated in this case of a 70-y-old man undergoing PET/CT for staging of squamous cell carcinoma of the right lung. It is important to report this finding during the evaluation of oncologic patients, to prevent severe complications that may arise from various oncologic interventions. PMID- 25125449 TI - Remote-controlled automatic injection versus manual injection in ictal SPECT of seizure patients: experience from a children's hospital. PMID- 25125450 TI - Bisphosphonate-associated atypical subtrochanteric femur fracture. AB - Bisphosphonates help prevent progressive bone mineralization loss and subsequent osteoporotic fractures. However, long-term bisphosphonate therapy paradoxically increases the risk of a unique injury called an atypical subtrochanteric femur fracture. Despite this, the benefits of bisphosphonates outweigh the risks, because far more pathologic fractures are prevented than induced. The early identification of atypical subtrochanteric femur fractures is important as there is high associated morbidity and mortality. We describe a case of a 76-y-old woman with a completed bisphosphonate-associated atypical subtrochanteric femur fracture. PMID- 25125451 TI - Examining the nuclear medicine advanced associate: past, present, and future-a white paper presented by members of the graduate stakeholders committee of the SNMMI technologist section. PMID- 25125452 TI - Frailty modeling for clustered competing risks data with missing cause of failure. AB - Competing risks data often occur within a center in multi-center clinical trials where the event times within a center may be correlated due to unobserved factors across individuals. In this paper, we consider the cause-specific proportional hazards model with a shared frailty to model the association between the event times within a center in the framework of competing risks. We use a hierarchical likelihood approach, which does not require any intractable integration over the frailty terms. In a clinical trial, cause of death information may not be observed for some patients. In such a case, analyses through exclusion of cases with missing cause of death may lead to biased inferences. We propose a hierarchical likelihood approach for fitting the cause-specific proportional hazards model with a shared frailty in the presence of missing cause of failure. We use multiple imputation methods to address missing cause of death information under the assumption of missing at random. Simulation studies show that the proposed procedures perform well, even if the imputation model is misspecified. The proposed methods are illustrated with data from EORTC trial 30791 conducted by European Organization for Research and Treatment of Cancer (EORTC). PMID- 25125453 TI - Sample size determinations for group-based randomized clinical trials with different levels of data hierarchy between experimental and control arms. AB - We derived sample size formulae for detecting main effects in group-based randomized clinical trials with different levels of data hierarchy between experimental and control arms. Such designs are necessary when experimental interventions need to be administered to groups of subjects whereas control conditions need to be administered to individual subjects. This type of trial, often referred to as a partially nested or partially clustered design, has been implemented for management of chronic diseases such as diabetes and is beginning to emerge more commonly in wider clinical settings. Depending on the research setting, the level of hierarchy of data structure for the experimental arm can be three or two, whereas that for the control arm is two or one. Such different levels of data hierarchy assume correlation structures of outcomes that are different between arms, regardless of whether research settings require two or three level data structure for the experimental arm. Therefore, the different correlations should be taken into account for statistical modeling and for sample size determinations. To this end, we considered mixed-effects linear models with different correlation structures between experimental and control arms to theoretically derive and empirically validate the sample size formulae with simulation studies. PMID- 25125455 TI - Comprehensive data on ionising radiation from Fukushima Daiichi nuclear power plant in the town of Miharu, Fukushima Prefecture: The Misho Project. AB - Data related to radioactivity released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu, Fukushima Prefecture, and by Tohoku University are presented. These data sets consist of (1) the earliest radiation monitoring by a Geiger counter in the town, (2) ratios of radioactivity between (132)Te and (137)Cs for a wide area between Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18 school grounds, and (4) external radiation exposure of 1400 students using OSL badges. By combining and analysing these various data sets, a curve for the cumulative total external exposure as a function of time, with 16 : 00 h on 15 March 2011 being time zero, is obtained. The average cumulative external dosage is estimated to be 10 mSv (sigma = 4.2 mSv) over 10 years. In addition, the initiative that the residents of Miharu took in response to the FDNPP accident, which became known as The Misho Project (MP), is documented; in particular, the time at which the municipality instructed the immediate ingestion of iodine tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed. PMID- 25125454 TI - Continuous glucose monitoring in insulin-treated patients in non-ICU settings. AB - Inpatient hyperglycemia, in patients with and without a history of diabetes, is associated with increased risk of complications, mortality, and longer hospital stay in medicine and surgical patients. Bedside capillary point of care testing is widely recommended as the preferred method for glucose monitoring and for guiding glycemic management of individual patients; however, the accuracy of most handheld glucose meters is far from optimal. Recent studies in the hospital setting have reported that the use of continuous glucose monitoring (CGM) can provide real-time information about glucose concentration, direction, and rate of change over a period of several days. Because it provides glucose values every 5 10 minutes 24 hours a day, CGM may have an advantage over point of care testing with respect to reducing the incidence of severe hypoglycemia in acute care. Real time CGM technology may facilitate glycemic control and to reduce hypoglycemia in insulin-treated patients. Recent guidelines, however, have recommended deferring the use of CGM in the adult hospital setting until further data on accuracy and safety become available. In this study, we review the advantages and disadvantages of the use of real-time CGM in the management of dysglycemia in the hospital setting. PMID- 25125456 TI - Foundations for literacy: An early literacy intervention for deaf and hard-of hearing children. AB - The present study evaluated the efficacy of a new preschool early literacy intervention created specifically for deaf and hard-of-hearing (DHH) children with functional hearing. Teachers implemented Foundations for Literacy with 25 DHH children in 2 schools (intervention group). One school used only spoken language, and the other used sign with and without spoken language. A "business as usual" comparison group included 33 DHH children who were matched on key characteristics with the intervention children but attended schools that did not implement Foundations for Literacy. Children's hearing losses ranged from moderate to profound. Approximately half of the children had cochlear implants. All children had sufficient speech perception skills to identify referents of spoken words from closed sets of items. Teachers taught small groups of intervention children an hour a day, 4 days a week for the school year. From fall to spring, intervention children made significantly greater gains on tests of phonological awareness, letter-sound knowledge, and expressive vocabulary than did comparison children. In addition, intervention children showed significant increases in standard scores (based on hearing norms) on phonological awareness and vocabulary tests. This quasi-experimental study suggests that the intervention shows promise for improving early literacy skills of DHH children with functional hearing. PMID- 25125457 TI - Cognitive and functional decline and their relationship in patients with mild Alzheimer's dementia. AB - BACKGROUND: In patients with Alzheimer's disease (AD), the relationship between cognitive and functional progression is not fully understood; however, functional decline has been postulated to follow cognitive decline. OBJECTIVE: To assess the relationship between cognitive and functional treatment effects in mild AD dementia patients. METHODS: Data of patients with mild AD were pooled from two multicenter, double-blind, Phase 3 studies. Patients were randomized to infusions of 400-mg solanezumab (n = 654), or placebo (n = 660) every 4 weeks for 18 months. Cognitive and functional outcome measures were assessed using the AD Assessment Scale-Cognitive subscale (ADAS-Cog) and the AD Cooperative Study Activities of Daily Living (ADCS-ADL), respectively. Analyses included comparisons among normalized scales, correlations between outcome measures, and path analyses to model the relationship of treatment effect on cognition and function. RESULTS: Normalized ADAS-Cog and ADCS-ADL scales showed cognitive impairment was more evident than functional impairment in mild AD. The correlation between cognition and function increased over time. Path analyses demonstrated that 87% of the treatment effect on function was driven by the treatment effect on cognition, with the remaining 13% due to direct treatment effect. CONCLUSION: Findings from this study are consistent with the hypothesis that functional impairment is primarily driven by and follows cognitive decline in mild AD dementia. The cognitive treatment effect appeared to explain the majority of the functional treatment effect. It is possible that a cognitive treatment effect may be considered as a leading indicator for functional outcomes in an 18-month clinical trial for milder stages of AD. PMID- 25125459 TI - Is brain copper deficiency in Alzheimer's, Lewy body, and Creutzfeldt Jakob diseases the common key for a free radical mechanism and oxidative stress-induced damage? AB - In Alzheimer's (AD), Lewy body (LBD), and Creutzfeldt Jakob (CJD) diseases, similar pathological hallmarks have been described, one of which is brain deposition of abnormal protease-resistant proteins. For these pathologies, copper bound to proteins is able to protect against free radicals by reduction from cupric Cu++ to cupreous Cu+. We have previously demonstrated in bovine brain homogenate that free radicals produce proteinase K-resistant prion after manganese is substituted for copper. Since low brain copper levels have been described in transmissible spongiform encephalopathies, in substantia nigra in Parkinson's disease, and in various brain regions in AD, LBD, and CJD, a mechanism has been proposed that may underlie the neurodegenerative processes that occur when copper protection against free radicals is impaired. In peptide sequences, the alpha acid proton near the peptide bond is highly mobile and can be pulled out by free radicals. It will produce a trivalent alpha-carbon radical and induce a free radical chain process that will generate a D-amino acid configuration in the peptide sequence. Since only L-amino acids are physiologically present in mammalian (human) proteins, it may be supposed that only physiological L-peptides can be recycled by physiological enzymes such as proteases. If a D-amino acid is found in the peptide sequence subsequent to deficient copper protection against free radicals, it will not be recognized and might alter the proteasome L-amino acid recycling from brain peptides. In the brain, there will result an accumulation of abnormal protease-resistant proteins such as those observed in AD, LBD, and CJD. PMID- 25125460 TI - Awareness of disease is different for cognitive and functional aspects in mild Alzheimer's disease: a one-year observation study. AB - Awareness of disease can be compromised to some degree in a proportion of people with dementia, with evident differences across domains. We designed this study to determine the factors associated with the impairment of awareness over a period of time. Using a longitudinal design, 69 people with mild Alzheimer's disease and their family caregivers completed the Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia, the Quality of Life in Alzheimer's Disease Scale, the Mini-Mental State Examination, the Clinical Dementia Rating Scale, the Cornell Scale for Depression in Dementia, the Pfeffer Functional Activities Questionnaire, the Neuropsychiatric Inventory, and the Zarit Burden Interview. Univariate and logistic regression analyses were conducted to examine the contribution of the various factors. The level of awareness of disease was significantly lower (p <= 0.001) between baseline and at follow up. At follow up, there was no change in the level of awareness of disease in 61.8%, whereas 25.4% worsened. However, the level of awareness improved in 12.3%. Logistic regression demonstrated that functional deficits (OR = 1.12, 95% CI: (1.03-1.22), p <= 0.01), and caregivers' quality of life (OR = 0.83, 95% CI: (0.70-0.98), p <= 0.05) were a significant predictor of impaired awareness of disease. The results confirmed that awareness and cognition are relatively independent, and showed that in people with mild dementia, unawareness is mainly manifested by poor recognition of changes in the activities of daily living, and decrease in quality of life. PMID- 25125458 TI - Global N-acetylaspartate in normal subjects, mild cognitive impairment and Alzheimer's disease patients. AB - BACKGROUND: Mild cognitive impairment (MCI) is an intermediary state on the way to Alzheimer's disease (AD). Little is known about whole brain concentration of the neuronal marker, N-acetylaspartate (NAA) in MCI patients. OBJECTIVE: To test the hypothesis that since MCI and AD are both neurodegenerative, quantification of the NAA in their whole brain (WBNAA) could differentiate them from cognitively intact matched controls. METHODS: Proton MR spectroscopy to quantify the WBNAA was applied to 197 subjects (86 females) 72.6 +/- 8.4 years old (mean +/- standard deviation). Of these, 102 were cognitively intact, 42 diagnosed as MCI, and 53 as probable AD. Their WBNAA amounts were converted into absolute concentration by dividing with the brain volume segmented from the MRI that also yielded the fractional brain volume (fBPV), an atrophy metric. RESULTS: WBNAA concentration of MCI and AD patients (10.5 +/- 3.0 and 10.1 +/- 2.9 mM) were not significantly different (p = 0.85). They were, however, highly significantly 25 29% lower than the 14.1 +/- 2.4 mM of normal matched controls (p < 10-4). The fBPV of MCI and AD patients (72.9 +/- 4.9 and 69.9 +/- 4.7%) differed significantly from each other (4%, p = 0.02) and both were significantly lower than the 74.6 +/- 4.4% of normal elderly (2%, p = 0.003 for MCI; 6%, p < 10-4 for AD). ROC curve analysis has shown WBNAA to have 70.5% sensitivity and 84.3% specificity to differentiate MCI or AD patients from normal elderly versus just 68.4 and 65.7% for fBPV. CONCLUSION: Low WBNAA in MCI patients compared with cognitively normal contemporaries may indicate early neuronal damage accumulation and supports the notion of MCI as an early stage of AD. It also suggests WBNAA as a potential marker of early AD pathology. PMID- 25125461 TI - Differences between mild cognitive impairment subtypes as indicated by event related potential correlates of cognitive and motor processes in a Simon task. AB - Mild cognitive impairment (MCI) may represent a prodromal stage of Alzheimer's disease (AD), although the clinical manifestations of MCI are heterogeneous. Consequently, MCI subtypes are differentiated since amnestic decline (particularly when combined with decline on multiple cognitive domains) increases the probability of progression to AD. In the present study, event-related potential (ERP) correlates of stimulus evaluation (N2), visuospatial attention (negativity posterior-contralateral, N2pc), stimulus categorization (P3b), executive control (pre-response positivity, PP, and medial frontal negativity), and motor (lateralized readiness potential, LRP) processes were studied in 53 participants while they performed a Simon task. Participants were divided into control group (CG), multiple-domain non-amnestic MCI (mdnaMCI), single-domain amnestic MCI (sdaMCI), and multiple-domain amnesic MCI (mdaMCI). Although there were no differences in reaction times and percentage of errors in the performed Simon-type task, a differential pattern of electrophysiological correlates was observed in MCI compared to CG. Concretely, amnestic MCI (sdaMCI and mdaMCI) showed reduced motor activity (LRP amplitude; AUC: 0.84); impairment in executive control (PP amplitude; AUC: 0.80) was observed in multiple-domain MCI (mdaMCI and mdnaMCI); finally, stimulus evaluation (N2 latency; AUC: 0.86) and visuospatial attention (N2pc amplitude; AUC: 0.78) was affected in mdaMCI. Overall, results linked the poorer prognosis of the mdaMCI subtype with a greater number of differences in ERP correlates regarding CG. Therefore, the present results enable us to suggest possible ERP biomarkers for specific MCI subtypes. PMID- 25125462 TI - Closing-in is related to apathy in Alzheimer's disease patients. AB - BACKGROUND: Apathy and depression are behavioral manifestations that may occur often in Alzheimer's disease (AD) patients. AD patients may also show Closing-in (CI) phenomenon, in graphic copying tasks. Recent evidence would suggest that apathetic symptoms are related to frontal dysfunctions in AD patients, whereas the cognitive bases of depressive symptoms in AD are still unclear. Recent studies demonstrated that frontal dysfunctions are also involved in the genesis of CI in AD patients. OBJECTIVE: Since frontal dysfunctions are thought to be more strongly related to apathetic than depressive symptoms, here we tested the hypothesis that CI is significantly associated with apathy in AD patients. METHODS: Forty-four AD patients were enrolled for this study. All patients completed a neuropsychological evaluation of visuo-spatial, frontal/executive, visuo-constructional, and memory skills. Moreover, graphic copying tasks were employed to detect CI, and behavioral scales to assess apathetic and depressive symptoms. RESULTS: CI and apathetic and depressed symptoms occurred in more than half of the present AD sample, but regression models revealed that the number of CI was significantly related to apathy only. The number of CI was also significantly correlated with severity of apathetic but not of depressive symptoms. CONCLUSION: The present study demonstrated that CI and apathy are correlated with each other in mild to moderate AD, likely because they share common pathogenic mechanisms related to frontal/executive dysfunctions. PMID- 25125463 TI - Cerebrospinal fluid alpha-synuclein and Lewy body-like symptoms in normal controls, mild cognitive impairment, and Alzheimer's disease. AB - BACKGROUND: Reduced cerebrospinal fluid (CSF) alpha-synuclein has been described in synucleinopathies, including dementia with Lewy bodies (DLB). Common symptoms of DLB include visual hallucinations and visuospatial and executive deficits. Co occurrence of Lewy body pathology is common in Alzheimer's disease (AD) patients, but it is unknown if reduced CSF alpha-synuclein is associated with Lewy body like symptomatology in AD. OBJECTIVE: Determine associations between CSF alpha synuclein and Lewy body-like symptomatology. METHODS: We included 73 controls (NC), 121 mild cognitive impairment (MCI) patients, and 61 AD patients (median follow-up 3.5 years, range 0.6-7.8). We tested associations between baseline CSF alpha-synuclein and visual hallucinations and (longitudinal) cognition. Models were tested with and without co-varying for CSF total tau (T-tau), which is elevated in AD patients, and believed to reflect neurodegeneration. RESULTS: Hallucinations were reported in 20% of AD patients, 13% of MCI patients, and 8% of NC. In AD, low CSF alpha-synuclein was associated with hallucinations. When adjusting for CSF T-tau, low CSF alpha-synuclein was associated with accelerated decline of executive function (NC, MCI, and AD), memory (MCI and AD), and language (MCI). CONCLUSION: The associations of low CSF alpha-synuclein with hallucinations and poor executive function, which are hallmarks of DLB, indirectly suggest that this biomarker may reflect underlying synuclein pathology. The associations with memory and language in MCI and AD suggests either that reduced CSF alpha-synuclein also partly reflects global impaired neuronal/synaptic function, or that non-specific overall cognitive deterioration is accelerated in the presence of synuclein related pathology. The findings will require autopsy verification. PMID- 25125465 TI - ABCA5 regulates amyloid-beta peptide production and is associated with Alzheimer's disease neuropathology. AB - Brain cholesterol homeostasis is regulated by a group of proteins called ATP binding cassette subfamily A (ABCA) transporters. Certain ABCA transporters regulate amyloid-beta protein precursor (AbetaPP) processing to generate amyloid beta peptides (Abeta) and are associated with an increased risk for late-onset Alzheimer's disease (AD). ABCA5 is a little-known member of the ABCA subfamily with no known function. In this study we undertook a comprehensive analysis of ABCA5 expression in the human and mouse brains. We explored the potential role of ABCA5 in AbetaPP processing associated with AD pathology. ABCA5 was differentially expressed in multiple regions of both human and mouse brains. It was strongly expressed in neurons with only weak expression in microglia, astrocytes, and oligodendrocytes. ABCA5 was able to stimulate cholesterol efflux in neurons. ABCA5 expression was specifically elevated in the hippocampus of AD brains. Using two in vitro cell systems we demonstrated that ABCA5 reduces Abeta production, both Abeta40 and Abeta42, without altering AbetaPP mRNA and protein levels, indicating that the decrease in the Abeta levels was due to changes in AbetaPP processing and not AbetaPP expression. This report represents the first extensive expression and functional study of ABCA5 in the human brain and our data suggest a plausible function of ABCA5 in the brain as a cholesterol transporter associated with Abeta generation, information that may offer a potential new target for controlling Abeta levels in the brain. PMID- 25125466 TI - Cerebrospinal fluid apolipoprotein E concentration and progression of Alzheimer's disease. AB - BACKGROUND/OBJECTIVE: Apolipoprotein E plays a role in the pathogenesis of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) and plasma level alterations have been reported in AD patients. In search of a potential biomarker, which would be predictive of cognitive, functional, or motor decline, we analyzed CSF apolipoprotein E (ApoE) levels of AD patients in this regard. METHODS: Subjects with newly diagnosed AD enrolled into an observational study were followed up longitudinally. Neuropsychological testing and physical examination were performed annually. In a sub-cohort of patients, where baseline CSF ApoE concentration values were available, multiple regression analyses were used to determine possible associations of CSF ApoE concentration and speed of decline on different cognitive, functional, and motor scales (MMSE, iADL, bADL, GDS, UPDRSIII) adjusting for possible confounders. RESULTS: No association of CSF ApoE levels and speed of decline on the various scales could be established (p = 0.09 to 0.88). Nevertheless, the use of neuroleptic drugs could be linked to higher velocity of global and extrapyramidal deterioration (p = 0.04 and 0.05 for GDS and UPDRSIII, respectively), but not to other outcomes (MMSE, bADL, and iADL). CONCLUSION: Herein, CSF ApoE at time of AD diagnosis could not be shown to be a viable biomarker for future cognitive, functional, or motor decline. Expectedly, the use of neuroleptic drugs was associated with detrimental effects. PMID- 25125464 TI - Increased tau phosphorylation and aggregation in the hippocampus of mice overexpressing corticotropin-releasing factor. AB - Clinical and basic science research suggests that stress and/or changes in central stress signaling intermediates may be involved in Alzheimer's disease (AD) pathogenesis. Although the links between stress and AD remain unsettled, data from our group and others have established that stress exposure in rodents may confer susceptibility to AD pathology by inducing hippocampal tau phosphorylation (tau-P). Work in our laboratory has shown that stress-induced tau P requires activation of the type-1 corticotropin-releasing factor receptor (CRFR1). CRF overexpressing (CRF-OE) mice are a model of chronic stress that display cognitive impairment at 9-10 month of age. In this study we used 6-7 month old CRF-OE mice to examine whether sustained exposure to CRF and stress steroids would impact hippocampal tau-P and kinase activity in the presence or absence of the CRFR1-specific antagonist, R121919, given daily for 30 days. CRF OE mice had significantly elevated tau-P compared to wild type (WT) mice at the AT8 (S202/T204), PHF-1 (S396/404), S262, and S422 sites. Treating CRF-OE mice with R121919 blocked phosphorylation at the AT8 (S202/T204) and PHF-1 (S396/404) sites, but not at the S262 and S422 sites and reduced phosphorylation of c-Jun N Terminal Kinase (JNK). Examination of hippocampal extracts from CRF-OE mice at the ultrastructural level revealed negatively stained round/globular aggregates that were positively labeled by PHF-1. These data suggest critical roles for CRF and CRFR1 in tau-P and aggregation and may have implications for the development of AD cognitive decline. PMID- 25125467 TI - Serum MHPG strongly predicts conversion to Alzheimer's disease in behaviorally characterized subjects with Down syndrome. AB - BACKGROUND: Down syndrome (DS) is the most prevalent genetic cause of intellectual disability. Early-onset Alzheimer's disease (AD) frequently develops in DS and is characterized by progressive memory loss and behavioral and psychological signs and symptoms of dementia (BPSD). Predicting and monitoring the progression of AD in DS is necessary to enable adaptive caretaking. OBJECTIVE: Reliable blood biomarkers that aid the prediction of AD are necessary, since cerebrospinal fluid sampling is rather burdensome, particularly for people with DS. Here, we investigate serum levels of eight biogenic amines and their metabolites in relation to dementia staging and probable BPSD items. METHODS: Using RP-HPLC with electrochemical detection, (nor)adrenergic (NA/A and MHPG), serotonergic (5-HT and 5-HIAA), and dopaminergic (DA, HVA, and DOPAC) compounds were quantified in the serum of DS subjects with established AD at baseline (n = 51), DS subjects without AD (n = 50), non-demented DS individuals that converted to AD over time (n = 50), and, finally, healthy non-DS controls (n = 22). RESULTS: Serum MHPG levels were significantly lower in demented and converted DS subjects (p < 0.0001) compared to non-demented DS individuals and healthy controls. Those subjects with MHPG levels below median had a more than tenfold increased risk of developing dementia. Furthermore, significant correlations were observed between monoaminergic serum values and various probable BPSD items within each DS group. CONCLUSION: Decreased serum MHPG levels show great potential as biomarker to monitor and predict conversion to AD in DS. Moreover, significant monoaminergic alterations related to probable BPSD items, suggesting that monoaminergic dysregulation is an underlying biological mechanism, and demonstrating the need to develop a validated rating scale for BPSD in DS. PMID- 25125469 TI - The microbiome and disease: reviewing the links between the oral microbiome, aging, and Alzheimer's disease. AB - This review, gathered from diverse sources, shows how our microbiome influences health and ultimately how well we age. Evidence linking oral bacteria to Alzheimer's disease (AD) is discussed in the context of aging, drawing together data from epidemiological, experimental, genetic, and environmental studies. Immunosenescence results in increased bacterial load as cell-mediated and humoral immune responses wane. The innate immune system gradually takes over; contributing to the rise in circulating proinflammatory cytokines such as TNFalpha. Maintaining the integrity of the blood-brain barrier (BBB) against a backdrop of increasing bacterial load is important. Aging may favor the proliferation of anaerobes in the mouth eliciting a robust TNFalpha response from the oral epithelium. Prolonged exposure to high levels of circulating TNFalpha compromises the integrity of the BBB. Sensitive techniques now detect the "asymptomatic" presence of bacteria in areas previously thought to be sterile, providing new insights into the wider distribution of components of the microbiome. These "immune-tolerated" bacteria may slowly multiply elsewhere until they elicit a chronic inflammatory response; some are now considered causal in instances of atherosclerosis and back pain. Inflammatory processes have long been associated with AD. We propose for a subset of AD patients, aging favors the overgrowth of oral anaerobes established earlier in life provoking a pro inflammatory innate response that weakens the BBB allowing bacteria to spread and quietly influence the pathogenesis of AD. Finally, we suggest that human polymorphisms considered alongside components of the microbiome may provide new avenues of research for the prevention and treatment of disease. PMID- 25125468 TI - Restoration of lipoxin A4 signaling reduces Alzheimer's disease-like pathology in the 3xTg-AD mouse model. AB - The initiation of an inflammatory response is critical to the survival of an organism. However, when inflammation fails to reach resolution, a chronic inflammatory state may occur, potentially leading to bystander tissue damage. Accumulating evidence suggests that chronic inflammation contributes to the progression of Alzheimer's disease (AD), and identifying mechanisms to resolve the pro-inflammatory environment stimulated by AD pathology remains an area of active investigation. Previously, we found that treatment with the pro-resolving mediator aspirin-triggered lipoxin A4 (ATL), improved cognition, reduced Abeta levels, and enhanced microglia phagocytic activity in Tg2576 transgenic AD mice. Here, we evaluated the effect of aging on brain lipoxin A4 (LXA4) levels using non-transgenic and 3xTg-AD mice. Additionally, we investigated the effect of ATL treatment on tau pathology in 3xTg-AD mice. We found that LXA4 levels are reduced with age, a pattern significantly more impacted in 3xTg-AD mice. Moreover, ATL delivery enhanced the cognitive performance of 3xTg-AD mice and reduced Abeta levels, as well as decreased the levels of phosphorylated-tau (p-tau). The decrease in p-tau was due in part to an inhibition of the tau kinases GSK-3beta and p38 MAPK. In addition, microglial and astrocyte reactivity was inhibited by ATL treatment. Our results suggest that the inability to resolve the immune response during aging might be an important feature that contributes to AD pathology and cognitive deficits. Furthermore, we demonstrate that activation of LXA4 signaling could serve as a potential therapeutic target for AD-related inflammation and cognitive dysfunction. PMID- 25125470 TI - Direct visualization of fungal infection in brains from patients with Alzheimer's disease. AB - Recently, we have reported the presence of fungal infections in patients with Alzheimer's disease (AD). Accordingly, fungal proteins and DNA were found in brain samples, demonstrating the existence of infection in the central nervous system. In the present work, we raised antibodies to specific fungal species and performed immunohistochemistry to directly visualize fungal components inside neurons from AD patients. Mice infected with Candida glabrata were initially used to assess whether yeast can be internalized in mammalian tissues. Using polyclonal rabbit antibodies against C. glabrata, rounded immunopositive cells could be detected in the cytoplasm of cells from liver, spleen, and brain samples in infected, but not uninfected, mice. Immunohistochemical analyses of tissue from the frontal cortex of AD patients revealed the presence of fungal material in a small percentage (~10%) of cells, suggesting the presence of infection. Importantly, this immunopositive material was absent in control samples. Confocal microscopy indicated that this fungal material had an intracellular localization. The specific morphology of this material varied between patients; in some instances, disseminated material was localized to the cytoplasm, whereas small punctate bodies were detected in other patients. Interestingly, fungal material could be revealed using different anti-fungal antibodies, suggesting multiple infections. In summary, fungal infection can only be observed using specific anti fungal antibodies and only a small percentage of cells contain fungi. Our findings provide an explanation for the hitherto elusive detection of fungi in AD brains, and are consistent with the idea that fungal cells are internalized inside neurons. PMID- 25125471 TI - Medication cost of persons with dementia in primary care in Germany. AB - BACKGROUND: Results of cost-of-illness studies in dementia have shown a considerable divergence in costs of medication for persons with dementia. However, detailed economic analyses of medication costs for community-dwelling persons with dementia are currently still missing, especially on the basis of primary data. OBJECTIVE: To determine medication cost, cost per drug, and number of drugs taken of community-dwelling persons with dementia and analyze their associated factors; to estimate the current price reduction of anti-dementia drugs due to implementation of low-priced generics. METHOD: The present analysis included 205 patients screened positive for dementia. Medication data were assessed within a medication review. To estimate the cost effect of implementing generics, the most favorable equivalent generic was assigned to each anti dementia drug. Factors associated with medication cost, cost per drug, and number of drugs taken were evaluated using multiple regression models. RESULTS: Medication cost and cost per drug were higher and the number of taken drugs lower in advanced stages of cognitive impairment. Prescription of anti-dementia generics could decrease overall medication cost by 28%. Medication cost was associated with number of diagnoses, deficits in activities of daily living, and age. Dementia severity was related to cost per drug and number of drugs taken. CONCLUSION: Medication cost increases with the number of diagnoses and growing deficits in activities of daily living and decreases with age. Severely cognitively impaired persons are treated with a small number of high-priced drugs, which could suggest inadequate medication of multimorbid persons. PMID- 25125472 TI - Rice bran extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer's disease. AB - Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer's disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of AD (PC12APPsw cells) releasing very low amyloid-beta (Abeta40) levels and thus mimicking early AD stages. Our data show that these cells have impaired energy metabolism, low ATP levels, and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1alpha as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo Pharmacol Res. (2013) 76C, 17-27. To assess the effect of RBE on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key components of RBE are oryzanols, tocopherols, and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production and respiratory rates as well as PGC1alpha protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of AD. PMID- 25125473 TI - Phosphodiesterase inhibition in cognitive decline. AB - Understanding the cellular and molecular processes involved in learning and memory will help in the development of safe and effective cognitive enhancers. The cAMP response element-binding (CREB) may be a universal modulator of processes required for memory formation, and increasing the levels of second messengers like cAMP and cGMP could ultimately lead to CREB activation. Phosphodiesterase (PDE) inhibitors regulate signaling pathways by elevating cAMP and/or cGMP levels, and they have been demonstrated to improve learning and memory in a number of rodent models of impaired cognition. The aim of this review is to summarize the outstanding progress that has been made in the application of PDE inhibitors for memory dysfunction. In addition, we have introduced some recent data we generated demonstrating that tadalafil could be considered as an optimal candidate for drug re-positioning and as a good candidate to enhance cognition. PMID- 25125474 TI - Enhanced neurite outgrowth and branching precede increased amyloid-beta-induced neuronal apoptosis in a novel Alzheimer's disease model. AB - Though it is widely accepted that amyloid-beta (Abeta) is a key factor in Alzheimer's disease (AD) pathology, its underlying mechanism remains unclear. In order to study the association between Abeta and neural circuitry dysfunction, we developed a primary culture preparation derived from the nervous system of transgenic Drosophila melanogaster larvae expressing human Abeta1-42 (Abeta42). Cultured neurons undergo a consistent developmental process, culminating in an elaborate neuronal network with distinct functional and morphological characteristics. Throughout this development, a time-dependent increase in intracellular expression levels of Abeta42 was detected, followed by extracellular staining at a later time point. When compared to controls, Abeta42 cultures exhibited enhanced levels of apoptosis, resulting in reduced cell viability. Moreover, as primary culture preparations enable high resolution monitoring of neuronal phenotypes, we were able to detect subtle morphological changes in neurons expressing Abeta42, namely an enhancement in neurite outgrowth and arborization, which preceded the effect of neurodegeneration. Our results establish D. melanogaster primary neuronal cultures as a rapid, accessible and cost-effective platform for AD molecular studies and drug screening, and suggest a possible role for Abeta42 in the organization of neuronal processes. PMID- 25125475 TI - Cannabis-based medicine reduces multiple pathological processes in AbetaPP/PS1 mice. AB - Several recent findings suggest that targeting the endogenous cannabinoid system can be considered as a potential therapeutic approach to treat Alzheimer's disease (AD). The present study supports this hypothesis demonstrating that delta 9-tetrahydrocannabinol (THC) or cannabidiol (CBD) botanical extracts, as well as the combination of both natural cannabinoids, which are the components of an already approved cannabis-based medicine, preserved memory in AbetaPP/PS1 transgenic mice when chronically administered during the early symptomatic stage. Moreover, THC + CBD reduced learning impairment in AbetaPP/PS1 mice. A significant decrease in soluble Abeta42 peptide levels and a change in plaques composition were also observed in THC + CBD-treated AbetaPP/PS1 mice, suggesting a cannabinoid-induced reduction in the harmful effect of the most toxic form of the Abeta peptide. Among the mechanisms related with these positive cognitive effects, the anti-inflammatory properties of cannabinoids may also play a relevant role. Here we observed reduced astrogliosis, microgliosis, and inflammatory-related molecules in treated AbetaPP/PS1 mice, which were more marked after treatment with THC + CBD than with either THC or CBD. Moreover, other cannabinoid-induced effects were uncovered by a genome-wide gene expression study. Thus, we have identified the redox protein thioredoxin 2 and the signaling protein Wnt16 as significant substrates for the THC + CBD-induced effects in our AD model. In summary, the present findings show that the combination of THC and CBD exhibits a better therapeutic profile than each cannabis component alone and support the consideration of a cannabis-based medicine as potential therapy against AD. PMID- 25125476 TI - Impaired lysosomal cobalamin transport in Alzheimer's disease. AB - Cobalamin (vitamin B12) is required for erythrocyte formation and DNA synthesis and it plays a crucial role in maintaining neurological function. As a coenzyme for methionine synthase and methylmalonyl-CoA mutase, cobalamin utilization depends on its efficient transit through the intracellular lysosomal compartment and subsequent delivery to the cytosol and mitochondria. Lysosomal function deteriorates in Alzheimer's disease (AD). Lysosomal acidification is defective in AD and lysosomal proteolysis is disrupted by AD-related presenilin 1 mutation. In this study, we propose that AD related lysosomal dysfunction may impair lysosomal cobalamin transport. The experiments use in vitro and in vivo models of AD to define how lysosomal dysfunction directly affects cobalamin utilization. SH-SY5Y AbetaPP mutant cells were treated with a proteasome inhibitor to induce lysosomal amyloid-beta accumulation. We metabolically labeled these cells with [57Co] cobalamin and isolated purified lysosomes, mitochondria, and cytosol fractions. The results indicated that proteasome inhibition was associated with lysosomal amyloid-beta accumulation and a doubling of lysosomal [57Co] cobalamin levels. We also used AbetaPPxPS1 transgenic AD mice that were intraperitoneally injected with [57Co] cobalamin. The amount of [57Co] cobalamin in the major organs of these mice was measured and the subcellular [57Co] cobalamin distribution in the brain was assessed. The results demonstrated that lysosomal [57Co] cobalamin level was significantly increased by 56% in the AbetaPPxPS1 AD mouse brains as compared to wild type control mice. Together these data provide evidence that lysosomal cobalamin may be impaired in AD in association with amyloid-beta accumulation. PMID- 25125477 TI - PKCepsilon deficits in Alzheimer's disease brains and skin fibroblasts. AB - In Alzheimer's disease (AD) transgenic mice, activation of synaptogenic protein kinase C epsilon (PKCepsilon) was found to prevent synaptotoxic amyloid-beta (Abeta)-oligomer elevation, PKCepsilon deficits, early synaptic loss, cognitive deficits, and amyloid plaque formation. In humans, to study the role of PKCepsilon in the pathophysiology of AD and to evaluate its possible use as an early AD-biomarker, we examined PKCepsilon and Abeta in the brains of autopsy confirmed AD patients (n = 20) and age-matched controls (AC, n = 19), and in skin fibroblast samples from AD (n = 14), non-AD dementia patients (n = 14), and AC (n = 22). Intraneuronal Abeta levels were measured immunohistochemically (using an Abeta-specific antibody) in hippocampal pyramidal cells of human autopsy brains. PKCepsilon was significantly lower in the hippocampus and temporal pole areas of AD brains, whereas Abeta levels were significantly higher. The ratio of PKCepsilon to Abeta in individual CA1 pyramidal cells was markedly lower in the autopsy AD brains versus controls. PKCepsilon was inversely correlated with Abeta levels in controls, whereas in AD patients, PKCepsilon showed no significant correlation with Abeta. In autopsy brains, PKCepsilon decreased as the Braak score increased. Skin fibroblast samples from AD patients also demonstrated a deficit in PKCepsilon compared to controls and an AD-specific change in the Abeta oligomer effects on PKCepsilon. Together, these data demonstrate that the relationship between Abeta levels and PKCepsilon is markedly altered in AD patients' brains and skin fibroblasts, reflecting a loss of protective effect of PKCepsilon against toxic Abeta accumulation. These changes of PKCepsilon levels in human skin fibroblasts may provide an accurate, non-invasive peripheral AD biomarker. PMID- 25125478 TI - The multiple lifestyle modification for patients with prehypertension and hypertension patients: a systematic review protocol. AB - INTRODUCTION: The objective of this systematic review is to investigate the effectiveness, efficacy and safety of multiple concomitant lifestyle modification therapies for patients with hypertension or prehypertension. METHODS AND ANALYSIS: Electronic searches will be performed in the Cochrane Library, OVID, EMBASE, etc, along with manual searches in the reference lists of relevant papers found during electronic search. We will identify eligible randomised controlled trials utilising multiple lifestyle modifications to lower blood pressure. The control could be drug therapy, single lifestyle change or no intervention. Changes in systolic blood pressure and diastolic blood pressure constitute primary end points, and secondary end points include the number of patients meeting the office target blood pressure, the number of patients reporting microvascular or macrovascular complications, etc. We will extract descriptive, methodological and efficacy data from identified randomised controlled trials (RCTs). We will calculate the relative risk for proportion of patients with a normal blood pressure in the experimental group. Dichotomous data will be analysed using risk difference and continuous data using weighted mean differences, both with 95% CI. We will use the chi(2) test and the I(2) statistic to assess heterogeneity. We will use the fixed effects model to compute the efficacy unless there is evidence of heterogeneity. If heterogeneity of effect size persists with respect to blood pressure change, further metaregression will be performed within groups. We will examine the potential for publication bias by using a funnel plot. DISSEMINATION: We will synthesise results from RCTs which provide more precise and accurate information on the effect of multiple lifestyle changes on blood pressure. The results of this review will increase the understanding of multiple lifestyle modifications for patients with hypertension or prehypertension. TRAIL REGISTRATION NUMBER: Our protocol is registered on PROSPERO (CRD42013006476), http://www.crd.your.ac.uk/PROSPERO. PMID- 25125479 TI - Potential risk of TNF inhibitors on the progression of interstitial lung disease in patients with rheumatoid arthritis. AB - OBJECTIVES: Biological therapy represents important advances in alleviating rheumatoid arthritis (RA), but the effect on interstitial lung disease (ILD) has been controversial. The objective of this study was to assess the risk of such treatment for patients with ILD. DESIGN: Case-control cohorts. SETTING: Single centre in Japan. PARTICIPANTS: This study included 163 patients with RA who underwent biological therapy. OUTCOME MEASURED: We assessed chest CT before initiation of biological therapy and grouped 163 patients according to the presence of ILD (with (n=58) and without pre-existing ILD (n=105)). Next, we evaluated serial changes of chest CT after treatment and visually assessed the emergence of ILD or its progression, which was referred to as an 'ILD event'. Then, we also classified the patients according to the presence of ILD events and analysed their characteristics. RESULTS: Tumour necrosis factor (TNF) inhibitors were administered to more patients with ILD events than those without ILD events (88% vs 60%, p<0.05), but recipients of tocilizumab or abatacept did not differ in this respect. Of 58 patients with pre-existing ILD, 14 had ILD events, and that proportion was greater than for those without pre-existing ILD (24% vs 3%, p<0.001). Of these 14 patients, all were treated with TNF inhibitors. Four patients developed generalised lung disease and two died from ILD progression. Baseline levels of KL-6 were similar in both groups, but increased in patients with ILD events. CONCLUSIONS: TNF inhibitors have the potential risk of ILD events, particularly for patients with pre-existing ILD, and KL-6 is a valuable surrogate marker for detecting ILD events. Our data suggest that non-TNF inhibitors are a better treatment option for these patients. PMID- 25125480 TI - Reduction in stillbirths at term after new birth induction paradigm: results of a national intervention. AB - OBJECTIVE: The risk of fetal death increases steeply after 42 gestational weeks. Since 2009, Denmark has had a more proactive policy including prevention of prolonged pregnancy, and early intervention in women with diabetes, preeclampsia, high body mass index and of a higher age group. The aim of this study was to describe the development in fetal deaths with this more proactive birth induction practice, and to identify and quantify contributing factors for this development. DESIGN: National cohort study. SETTING: Denmark. PARTICIPANTS: Delivering women in Denmark, 1 January 2000 to 31 December 2012. OUTCOME MEASURES: Stillbirths per 1000 women at risk (prospective risk of stillbirth) and per 1000 newborn from 37 and 40 gestational weeks, respectively, through the study period. RESULTS: During the study period, 829,165 children were live born and 3770 (0.45%) stillborn. Induction of labour increased from 12.4% in year 2000 to 25.1% in 2012 (p<0.001), and the percentage of children born at or after 42 weeks decreased from 8.0% to 1.5% (p<0.001). Through the same period, the prospective risk of stillbirth after 37 weeks fell from 0.70 to 0.41/1000 ongoing pregnancies (p<0.001), and from 2.4 to 1.4/1000 newborn (p<0.001). The regression analysis confirmed the inverse association between year of birth and risk of stillbirth. The lowest risk was observed in the years 2011-2012 as compared with years 2000-2002 with a fully adjusted HR of 0.69 (95% CI 0.57 to 0.83). The general earlier induction, the focused earlier induction of women with body mass index >30, twins, and of women above 40 years and a halving of smoking pregnant women were all independent contributing factors for the decrease. CONCLUSIONS: A gradually more proactive and differential earlier labour induction practice is likely to have mainly been responsible for the substantial reduction in stillbirths in Denmark. PMID- 25125482 TI - Preclinical characterization of 5-amino-4-oxo-[6-11C]hexanoic acid as an imaging probe to estimate protoporphyrin IX accumulation induced by exogenous aminolevulinic acid. AB - Preoperative noninvasive imaging to estimate the quantity and spatial distribution of protoporphyrin IX (PpIX) accumulation in tumors induced by 5 aminolevulinic acid (ALA) administration is expected to improve the efficacy of ALA-based fluorescence-guided resection and photo- and sonodynamic therapies. PpIX synthesis from exogenous ALA has been reported to be regulated by ALA influx or ALA dehydratase (ALAD) activity, which catalyzes the first step of the synthesis. In this study, we characterized the properties of a (11)C-labeled ALA analog, 5-amino-4-oxo-[6-(11)C]hexanoic acid ((11)C-MALA), as a PET tracer to estimate PpIX accumulation. METHODS: In vitro uptake of (11)C-MALA and (3)H-ALA was determined in 5 tumor cell lines after 10-min incubation with each tracer at 37 degrees C. The expression levels of ALAD were determined by Western blot analysis. In vivo distribution and dynamic PET studies were conducted in tumor bearing mice. In vitro and in vivo accumulation of ALA-induced PpIX was determined by measuring fluorescence in extracts of cells or tumors. RESULTS: In vitro uptake of (11)C-MALA in 5 tumor cell lines was correlated with ALAD expression levels and PpIX accumulation. In vivo biodistribution and dynamic PET studies showed that (11)C-MALA was rapidly incorporated into tumors, and the tumor-to-muscle ratio of (11)C-MALA at 1 min after injection was significantly correlated with that of (3)H-ALA. (11)C-MALA in tumors was continuously decreased thereafter, and the elimination rate of (11)C-MALA from AsPC-1 tumors with the highest ALAD expression level was slower than from other tumors with lower expression levels. These results suggest that the influx and intracellular retention of (11)C-MALA reflect ALA influx and ALAD expression levels, respectively. Tumor accumulation of (11)C-MALA at 60 min after injection was strongly correlated with PpIX accumulation in tumor tissues. CONCLUSION: (11)C MALA PET has the potential to noninvasively estimate the quantitative and spatial accumulation of exogenous ALA-induced PpIX. PMID- 25125481 TI - Comparison of the amino acid tracers 18F-FET and 18F-DOPA in high-grade glioma patients. AB - High-grade gliomas (HGGs) are the most common malignant primary tumors of the central nervous system. PET probes of amino acid transport such as O-(2-(18)F fluoroethyl)-l-tyrosine ((18)F-FET), 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine ((18)F-DOPA), and (11)C-methionine ((11)C-MET) detect primary and recurrent tumors with a high accuracy. (18)F-FET is predominantly used in Europe, whereas amino acid transport imaging is infrequently done in the United States. The aim of this study was to determine whether (18)F-FET and (18)F-DOPA PET/CT provide comparable information in HGG. METHODS: Thirty (18)F-FET and (18)F-DOPA PET/CT scans were obtained before surgery or biopsy in 27 patients with high clinical suspicion for primary or recurrent HGG (5 primary, 22 recurrent tumors). (18)F FET and (18)F-DOPA PET/CT images were compared visually and semiquantitatively (maximum standardized uptake value [SUV(max)], mean SUV [SUV(mean)]). Background (SUV(max) and SUV(mean)) and tumor-to-background ratios (TBRs) were calculated for both PET probes. The degree of (18)F-DOPA uptake in the basal ganglia (SUV(mean)) was also assessed. RESULTS: Visual analysis revealed no difference in tumor uptake pattern between the 2 PET probes. The SUV(mean) and SUV(max) for (18)F-FET were higher than those of (18)F-DOPA (4.0 +/- 2.0 and 4.9 +/- 2.3 vs. 3.5 +/- 1.6 and 4.3 +/- 2.0, respectively; all P < 0.001). TBRs for SUV(mean) but not for SUV(max) were significantly higher for (18)F-FET than (18)F-DOPA (TBR SUV(mean): 3.8 +/- 1.7 vs. 3.4 +/- 1.2, P = 0.004; TBR SUV(max): 3.3 +/- 1.6 and 3.0 +/- 1.1, respectively; P = 0.086). (18)F-DOPA uptake by the basal ganglia was present (SUV(mean), 2.6 +/- 0.7) but did not affect tumor visualization. CONCLUSION: Whereas visual analysis revealed no significant differences in uptake pattern for (18)F-FET and (18)F-DOPA in patients with primary or recurrent HGG, both SUVs and TBRs for SUV(mean) were significantly higher for (18)F-FET. However, regarding tumor delineation, both tracers performed equally well and seem equally feasible for imaging of primary and recurrent HGG. These findings suggest that both PET probes can be used based on availability in multicenter trials. PMID- 25125483 TI - Iatrogenic parkinsonism: the role of flunarizine and cinnarizine. AB - We performed a clinical report based, descriptive and retrospective study, aimed at comparing Flunarizine/Cinnarizine-induced parkinsonism (FCIP) patients and Parkinson's disease (PD) patients. The FCIP group (n = 30) presented a lower frequency of rigidity and unilateral tremor than the PD group (n = 70). All FCIP patients improved, 13 after dopaminergic treatment. FCIP patients who improved spontaneously presented lower frequency of rigidity, compared with the other FCIP subgroup and PD group. FCIP patients who did not improve spontaneously showed a clinical pattern similar to PD patients. PMID- 25125484 TI - Medio-lateral balance impairment differentiates between Parkinson's disease and atypical parkinsonism. AB - In early disease stages, it can be difficult to differentiate clinically between Parkinson's disease and the various forms of atypical parkinsonism, like multiple system atrophy or progressive supranuclear palsy. Balance impairment in the medio lateral plane (i.e. sideways) is often seen in patients with a form of atypical parkinsonism, but not in patients with Parkinson's disease. This is reflected by the distance between the feet during gait, which is typically normal (or even narrow) in Parkinson's disease, but widened in atypical parkinsonism. Estimating this stance width depends on subjective judgement, and is difficult to quantify in clinical practice. Here, we emphasize that this medio-lateral balance impairment can also be revealed using two simple tests: (1) inability to perform tandem gait (taking one or more side steps being abnormal); and (2) self-report by patients who have lost the ability to ride a bicycle. Both tests have a good diagnostic yield in differentiating between Parkinson's disease and atypical parkinsonism, even early in the course of the disease. PMID- 25125485 TI - Tumor-associated macrophages as major players in the tumor microenvironment. AB - During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy. PMID- 25125486 TI - Distinct networks of leptin- and insulin-sensing neurons regulate thermogenic responses to nutritional and cold challenges. AB - Defense of core body temperature (Tc) can be energetically costly; thus, it is critical that thermoregulatory circuits are modulated by signals of energy availability. Hypothalamic leptin and insulin signals relay information about energy status and are reported to promote thermogenesis, raising the possibility that they interact to direct an appropriate response to nutritional and thermal challenges. To test this idea, we used an Nkx2.1-Cre driver to generate conditional knockouts (KOs) in mice of leptin receptor (L(2.1)KO), insulin receptor (I(2.1)KO), and double KOs of both receptors (D(2.1)KO). L(2.1)KOs are hyperphagic and obese, whereas I(2.1)KOs are similar to controls. D(2.1)KOs exhibit higher body weight and adiposity than L(2.1)KOs, solely due to reduced energy expenditure. At 20-22 degrees C, fed L(2.1)KOs maintain a lower baseline Tc than controls, which is further decreased in D(2.1)KOs. After an overnight fast, some L(2.1)KOs dramatically suppress energy expenditure and enter a torpor like state; this behavior is markedly enhanced in D(2.1)KOs. When fasted mice are exposed to 4 degrees C, L(2.1)KOs and D(2.1)KOs both mount a robust thermogenic response and rapidly increase Tc. These observations support the idea that neuronal populations that integrate information about energy stores to regulate the defense of Tc set points are distinct from those required to respond to a cold challenge. PMID- 25125487 TI - Loss-of-function mutations in ABCA1 and enhanced beta-cell secretory capacity in young adults. AB - Loss-of-function mutations affecting the cholesterol transporter ATP-binding cassette transporter subfamily A member 1 (ABCA1) impair cellular cholesterol efflux and are associated with reduced HDL-cholesterol (HDL-C) levels. ABCA1 may also be important in regulating beta-cell cholesterol homeostasis and insulin secretion. We sought to determine whether loss-of-function ABCA1 mutations affect beta-cell secretory capacity in humans by performing glucose-potentiated arginine tests in three subjects homozygous for ABCA1 mutations (age 25 +/- 11 years), eight heterozygous subjects (28 +/- 7 years), and eight normal control subjects pair-matched to the heterozygous carriers. To account for any effect of low HDL-C on insulin secretion, we studied nine subjects with isolated low HDL-C with no ABCA1 mutations (age 26 +/- 6 years) and nine pair-matched control subjects. Homozygotes for ABCA1 mutations exhibited enhanced oral glucose tolerance and dramatically increased beta-cell secretory capacity that was also greater in ABCA1 heterozygous subjects than in control subjects, with no differences in insulin sensitivity. Isolated low HDL-C subjects also demonstrated an increase in beta-cell secretory capacity but in contrast to those with ABCA1 mutations, exhibited impaired insulin sensitivity, supporting beta-cell compensation for increased insulin demand. These data indicate that loss-of-function mutations in ABCA1 in young adults may be associated with enhanced beta-cell secretory capacity and normal insulin sensitivity and support the importance of cellular cholesterol homeostasis in regulating beta-cell insulin secretion. PMID- 25125489 TI - Public service stress and burnout over 12 months. AB - BACKGROUND: Research indicates that workplace stress has the potential to harm employee health with stress and stress-related absence increasing significantly during economic recession and times of organizational change. AIMS: To explore whether psychosocial hazards and burnout changed over a 12 month period in a public sector organization during a period of severely reduced organizational finances. METHODS: The Management Standards Indicator Tool (MSIT) and the Maslach Burnout Inventory-General Scale (MBI-GS) were administered to employees of one local government department in July 2011 and July 2012. RESULTS: A total of 128 employees completed the questionnaires in July 2011 (response rate 67%) and 57 in July 2012 (response rate 54%). MSIT factor scores of demands, peer support and role worsened significantly over the period of study. Furthermore, all psychosocial hazards scored worse than the recommended level set by Health and Safety Executive. Two burnout dimensions, 'demands' and 'cynicism', significantly worsened over the 12 month period but professional efficacy increased. CONCLUSIONS: The MSIT and MBI-GS appeared to have utility in this comparison. Psychosocial hazards appeared to worsen over the 12 months of the study, as 'demands' and 'cynicism' increased. However, an increase in professional efficacy was also seen, which requires further investigation. PMID- 25125490 TI - Integrating attachment and depression in the confluence model of sexual assault perpetration. AB - This study sought to extend the confluence model of sexual assault perpetration by examining attachment insecurity and depression as additional predictors of sexual aggression. Male college students (N = 193) completed an online questionnaire assessing confluence model constructs in addition to attachment and history of depression. Overall, the model fit the data well, chi(2)(11, 193) = 19.43, p = ns; root mean square error of approximation = .063; comparative fit index = .94. Attachment and depression demonstrated both direct and indirect relationships with perpetration severity. The results contribute to elucidating the process by which certain men become susceptible to perpetrating sexual assault. Implications are discussed. PMID- 25125488 TI - Mineralocorticoid receptor blockade improves coronary microvascular function in individuals with type 2 diabetes. AB - Reduced coronary flow reserve (CFR), an indicator of coronary microvascular dysfunction, is seen in type 2 diabetes mellitus (T2DM) and predicts cardiac mortality. Since aldosterone plays a key role in vascular injury, the aim of this study was to determine whether mineralocorticoid receptor (MR) blockade improves CFR in individuals with T2DM. Sixty-four men and women with well-controlled diabetes on chronic ACE inhibition (enalapril 20 mg/day) were randomized to add on therapy of spironolactone 25 mg, hydrochlorothiazide (HCTZ) 12.5 mg, or placebo for 6 months. CFR was assessed by cardiac positron emission tomography at baseline and at the end of treatment. There were significant and similar decreases in systolic blood pressure with spironolactone and HCTZ but not with placebo. CFR improved with treatment in the spironolactone group as compared with the HCTZ group and with the combined HCTZ and placebo groups. The increase in CFR with spironolactone remained significant after controlling for baseline CFR, change in BMI, race, and statin use. Treatment with spironolactone improved coronary microvascular function, raising the possibility that MR blockade could have beneficial effects in preventing cardiovascular disease in patients with T2DM. PMID- 25125491 TI - Interview interruption and responses to questions about domestic violence in India. AB - This article uses the National Family Health Survey 2005-2006 (NFHS-3) of India to examine the relationship between interview interruption and the reporting of domestic violence. A sample of 65,610 currently married women was used to compare reported acts of physical and sexual violence among women who had been interrupted during their interview and those who had not. Logistic regression analyses indicated that women whose interviews were interrupted by either an adult man or woman were significantly more likely to report intimate partner violence. PMID- 25125492 TI - The explanatory role of relationship power and control in domestic violence against women in Nicaragua: a feminist psychology analysis. AB - This study offers a feminist psychology analysis of various aspects of relationship power and control and their relative explanatory contribution to understanding physical, psychological, and sexual violence against women. Findings from structured interviews with 345 women from rural Nicaragua (M age = 44) overwhelmingly demonstrate that measures of power and control reflecting interpersonal relationship dynamics have the strongest predictive power for explaining violence when compared in multivariate analyses to several of the more commonly used measures. These findings have implications for future research and the evaluation of interventions designed to decrease levels of violence against women. PMID- 25125493 TI - Evaluation of the Green Dot Bystander Intervention to Reduce Interpersonal Violence Among College Students Across Three Campuses. AB - Evidence suggests that interventions to engage bystanders in violence prevention increase bystander intentions and efficacy to intervene, yet the impact of such programs on violence remains unknown. This study compared rates of violence by type among undergraduate students attending a college campus with the Green Dot bystander intervention (n = 2,768) with students at two colleges without bystander programs (n = 4,258). Violent victimization rates were significantly (p < .01) lower among students attending the campus with Green Dot relative to the two comparison campuses. Violence perpetration rates were lower among males attending the intervention campus. Implications of these results for research and practice are discussed. PMID- 25125494 TI - Extending Johnson's intimate partner violence typology: lessons from an adolescent sample. AB - Johnson's intimate partner violence (IPV) typology-categorizing IPV by both use and receipt of physical violence and controlling behaviors-effectively predicts IPV consequences among adults. His typology has not yet been applied to adolescents, an important population for early IPV intervention. Therefore, in analyzing IPV covariates among 493 female urban high school students, we used as key predictors both Johnson's original typology and, for enhanced clarity, a relationship-level extension. Preliminary evidence suggests that the pattern of adolescent IPV differs substantially from that of adult IPV and that a relationship-level typology provided additional clarity in categorizing this pattern. PMID- 25125495 TI - miR-1, miR-133a/b, and miR-208a in human fetal hearts correlate to the apoptotic and proliferation markers. AB - The heart is the first organ to function in the developing embryo. MicroRNAs (miRNAs) are small non-coding RNAs involved in the translational regulation of gene expression, which is beside transcriptional regulation crucial for the morphologic development of muscle tissue. The aim of our study was to test the hypothesis that the expression of miR-1, miR-133a/b, and miR-208a correlates with gestational age as well as with an apoptotic and proliferative index in the developing human heart. Our study included normal heart tissue samples obtained at autopsy from 46 fetuses, 12 children, and 15 adults. Proliferation and apoptosis were measured by the immunohistochemical detection of Ki67 and cleaved CK18. Expression of miR-1, miR-133a, miR-133b, and miR-208a was measured using real-time PCR. We found a similar level of expression of miR-133a/b in fetal and children hearts that was different from the levels in healthy adults. We also found a correlation between a miR-208a expression to the gestational age of fetuses. We observed an inverse correlation between Ki67 expression and gestational age. Expression of Ki67 was positively correlated to the expression of miR-208a and miR-1, but inversely correlated to the expression of miR-133a/b. Expression of cleaved-CK18 was also inversely correlated to the expression of miR 133a/b. Our results showed a general decrease in the expression of miR-1 and an increase of miR-133a/b with increasing gestational age. We also found a general decrease in the expression of miR-208a, mimicking the expression of its host gene. Our results also suggest the involvement of miR-208a and miR-1 in the proliferation as well as anti-proliferative and anti-apoptotic roles of miR 133a/b. PMID- 25125496 TI - Combination of honokiol and magnolol inhibits hepatic steatosis through AMPK SREBP-1 c pathway. AB - Honokiol and magnolol, as pharmacological biphenolic compounds of Magnolia officinalis, have been reported to have antioxidant and anti-inflammatory properties. Sterol regulatory element binding protein-1 c (SREBP-1 c) plays an important role in the development and processing of steatosis in the liver. In the present study, we investigated the effects of a combination of honokiol and magnolol on SREBP-1 c-dependent lipogenesis in hepatocytes as well as in mice with fatty liver due to consumption of high-fat diet (HFD). Liver X receptor alpha (LXRalpha) agonists induced activation of SREBP-1 c and expression of lipogenic genes, which were blocked by co-treatment of honokiol and magnolol (HM). Moreover, a combination of HM potently increased mRNA of fatty acid oxidation genes. HM induced AMP-activated protein kinase (AMPK), an inhibitory kinase of the LXRalpha-SREBP-1 c pathway. The role of AMPK activation induced by HM was confirmed using an inhibitor of AMPK, Compound C, which reversed the ability of HM to both inhibit SREBP-1 c induction as well as induce genes for fatty acid oxidation. In mice, HM administration for four weeks ameliorated HFD induced hepatic steatosis and liver dysfunction, as indicated by plasma parameters and Oil Red O staining. Taken together, our results demonstrated that a combination of HM has beneficial effects on inhibition of fatty liver and SREBP 1 c-mediated hepatic lipogenesis, and these events may be mediated by AMPK activation. PMID- 25125497 TI - Dengue virus infection induces broadly cross-reactive human IgM antibodies that recognize intact virions in humanized BLT-NSG mice. AB - The development of small animal models that elicit human immune responses to dengue virus (DENV) is important since prior immunity is a major risk factor for developing severe dengue disease. This study evaluated anti-DENV human antibody (hAb) responses generated from immortalized B cells after DENV-2 infection in NOD scid IL2rgamma(null) mice that were co-transplanted with human fetal thymus and liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the IgM isotype were isolated during acute infection and in convalescence. We found that while a few hAbs recognized the envelope protein produced as a soluble recombinant, a number of hAbs only recognized epitopes on intact virions. The majority of the hAbs isolated during acute infection and in immune mice were serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG mice were significantly decreased after challenge with a clinical strain of dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the characteristics of Abs isolated in humans with natural infection. Humanized BLT NSG mice provide an attractive preclinical platform to assess the immunogenicity of candidate dengue vaccines. PMID- 25125498 TI - Phosphodiesterase 5 inhibitors augment UT-15C-stimulated ATP release from erythrocytes of humans with pulmonary arterial hypertension. AB - Both prostacyclin analogs and phosphodiesterase 5 (PDE5) inhibitors are effective treatments for pulmonary arterial hypertension (PAH). In addition to direct effects on vascular smooth muscle, prostacyclin analogs increase cAMP levels and ATP release from healthy human erythrocytes. We hypothesized that UT-15C, an orally available form of the prostacyclin analog, treprostinil, would stimulate ATP release from erythrocytes of humans with PAH and that this release would be augmented by PDE5 inhibitors. Erythrocytes were isolated and the effect of UT-15C on cAMP levels and ATP release were measured in the presence and absence of the PDE5 inhibitors, zaprinast or tadalafil. In addition, the ability of a soluble guanylyl cyclase inhibitor to prevent the effects of tadalafil was determined. Erythrocytes of healthy humans and humans with PAH respond to UT-15C with increases in cAMP levels and ATP release. In both groups, UT-15C-induced ATP release was potentiated by zaprinast and tadalafil. The effect of tadalafil was prevented by pre-treatment with an inhibitor of soluble guanylyl cyclase in healthy human erythrocytes. Importantly, UT-15C-induced ATP release was greater in PAH erythrocytes than in healthy human erythrocytes in both the presence and the absence of PDE5 inhibitors. The finding that prostacyclin analogs and PDE5 inhibitors work synergistically to enhance release of the potent vasodilator ATP from PAH erythrocytes provides a new rationale for the co-administration of these drugs in this disease. Moreover, these results suggest that the erythrocyte is a novel target for future drug development for the treatment of PAH. PMID- 25125499 TI - Ursodeoxycholyl lysophosphatidylethanolamide inhibits cholestasis- and hypoxia induced apoptosis by upregulating antiapoptosis proteins. AB - An increase of toxic bile acids such as glycochenodeoxycholic acid occurs during warm ischemia reperfusion causing cholestasis and damage in hepatocytes and intrahepatic biliary epithelial cells. We aim to test antiapoptosis effects of ursodeoxycholyl lysophosphatidylethanolamide under cholestatic induction by glycochenodeoxycholic acid treatment of mouse hepatocytes and hypoxia induction by cobalt chloride treatment of intrahepatic biliary epithelial cancer Mz-ChA 1cell line. Such treatments caused marked increases in apoptosis as evidenced by activation of caspase 3, caspase 8 and poly (ADP-ribose) polymerase-1. Co treatment with ursodeoxycholyl lysophosphatidylethanolamide significantly inhibited these increases. Interestingly, ursodeoxycholyl lysophosphatidylethanolamide was able to increase expression of antiapoptotic cellular FLICE-inhibitory protein in both cell types. Ursodeoxycholyl lysophosphatidylethanolamide also prevented the decreases of myeloid cell leukemia sequence-1 protein in both experimental systems, and this protection was due to ursodeoxycholyl lysophosphatidylethanolamide's ability to inhibit ubiquitination-mediated degradation of myeloid cell leukemia sequence-1, and to increase the phosphorylation of GSK-3beta. In addition, ursodeoxycholyl lysophosphatidylethanolamide was able to prevent the decreased expression of another antiapoptotic cellular inhibitor of apoptosis 2 in cobalt chloride treated Mz-ChA-1 cells. Hence, ursodeoxycholyl lysophosphatidylethanolamide mediated cytoprotection against apoptosis during toxic bile-acid and ischemic stresses by a mechanism involving accumulation of cellular FLICE-inhibitory protein, myeloid cell leukemia sequence-1 and cellular inhibitor of apoptosis 2 proteins. Ursodeoxycholyl lysophosphatidylethanolamide may thus be used as an agent to prevent hepatic ischemia reperfusion. PMID- 25125500 TI - Preparation and antitumor effect of a toxin-linked conjugate targeting vascular endothelial growth factor receptor and urokinase plasminogen activator. AB - The aberrant signaling activation of vascular endothelial growth factor receptor (VEGFR) and urokinase plasminogen activator (uPA) is a common characteristic of many tumors, including lung cancer. Accordingly, VEGFR and uPA have emerged as attractive targets for tumor. KDR (Flk-1/VEGFR-2), a member of the VEGFR family, has been recognized as an important target for antiangiogenesis in tumor. In this study, a recombinant immunotoxin was produced to specifically target KDR expressing tumor vascular endothelial cells and uPA-expressing tumor cells and mediate antitumor angiogenesis and antitumor effect. Based on its potent inhibitory effect on protein synthesis, Luffin-beta (Lbeta) ribosome-inactivating protein was selected as part of a recombinant fusion protein, a single-chain variable fragment against KDR (KDRscFv)-uPA cleavage site (uPAcs)-Lbeta-KDEL (named as KPLK). The KDRscFv-uPAcs-Lbeta-KDEL (KPLK) contained a single-chain variable fragment (scFv) against KDR, uPAcs, Lbeta, and the retention signal for endoplasmic reticulum proteins KDEL (Lys-Asp-Glu-Leu). The KPLK-expressing vector was expressed in Escherichia coli, and the KPLK protein was isolated with nickel affinity chromatography and gel filtration chromatography. Sodium dodecyl sulfate polyacrylamide gel electrophoresis test demonstrated KPLK was effectively expressed. Result of in vitro cell viability assay on non-small cell lung cancer (NSCLC) H460 cell line (uPA-positive cell) revealed that KPLK significantly inhibited cell proliferation, induced apoptosis, and accumulated cells in S and G2/M phases, but the normal cell line (human submandibular gland cell) was unaffected. These effects were enhanced when uPA was added to digest KPLK to release Lbeta. For in vivo assay of KPLK, subcutaneous xenograft tumor model of nude mice were established with H460 cells. Growth of solid tumors was significantly inhibited in animals treated with KPLK up to 21 days, tumor weights were decreased, and the expression of angiogenesis marker CD31 was downregulated; meanwhile, the apoptosis-related protein casspase-3 was upregulated. These results suggested that the recombinant KPLK may have therapeutic applications on tumors, especially uPA-overexpressing ones. PMID- 25125502 TI - Effect of perceived stress on cytokine production in healthy college students. AB - Chronic psychological stress impairs antibody synthesis following influenza vaccination. Chronic stress also increases circulating levels of proinflammatory cytokines and glucocorticoids in elders and caregivers, which can impair antibody synthesis. The purpose of this study was to determine whether psychological stress increases ex vivo cytokine production or decreases glucocorticoid sensitivity (GCS) of peripheral blood leukocytes from healthy college students. A convenience sample of Reserve Officer Training Corps (ROTC) students completed the Perceived Stress Scale (PSS). Whole blood was incubated in the presence of influenza vaccine and dexamethasone to evaluate production of interleukin-6 (IL 6), interleukin-1-beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). Multiple regression models controlling for age, gender, and grade point average revealed a negative relationship between PSS and GCS for vaccine-stimulated production of IL-1beta, IL-6, and TNF-alpha. These data increase our understanding of the complex relationship between chronic stress and immune function. PMID- 25125501 TI - Telmisartan induces apoptosis and regulates Bcl-2 in human renal cancer cells. AB - It has been well-characterized that the renin-angiotensin system (RAS) physiologically regulates systemic arterial pressure. However, RAS signaling has also been shown to increase cell proliferation during malignancy, and angiotensin receptor blockers (ARBs) are able to decrease pro-survival signaling by inhibiting anti-apoptotic molecules and suppressing caspase activity. In this study, the apoptotic effects of telmisartan, a type of ARB, was evaluated using a non-cancerous human renal cell line (HEK) and a human renal cell carcinoma (RCC) cell line (786). Both types of cells were treated with telmisartan for 4 h, 24 h, and 48 h, and then were assayed for levels of apoptosis, caspase-3, and Bcl-2 using MTT assays, flow cytometry, and immunostaining studies. Analysis of variance was used to identify significant differences between these data (P < 0.05). Following the treatment of 786 cells with 100 uM and 200 uM telmisartan, a marked inhibition of cell proliferation was observed. 50 uM cisplatin also caused high inhibition of these cells. Moreover, these inhibitions were both concentration- and time-dependent (P < 0.05). Various apoptotic effects were also observed compared with control cells at the 24 h and 48 h timepoints assayed (P < 0.001). Furthermore, positive caspase-3 staining and down-regulation of Bcl-2 were detected, consistent with induction of cell death. In contrast, treatment of HEK cells with telmisartan did not produce an apoptotic effect compared with control cells at the 24 h timepoint (P > 0.05). Treatment with cisplatin promoted in HEK cells high index of apoptosis (P < 0.001). Taken together, these results suggest that telmisartan induces apoptosis via down-regulation of Bcl-2 and involvement of caspase-3 in human RCC cells. PMID- 25125503 TI - Tomato fruit chromoplasts behave as respiratory bioenergetic organelles during ripening. AB - During tomato (Solanum lycopersicum) fruit ripening, chloroplasts differentiate into photosynthetically inactive chromoplasts. It was recently reported that tomato chromoplasts can synthesize ATP through a respiratory process called chromorespiration. Here we show that chromoplast oxygen consumption is stimulated by the electron donors NADH and NADPH and is sensitive to octyl gallate (Ogal), a plastidial terminal oxidase inhibitor. The ATP synthesis rate of isolated chromoplasts was dependent on the supply of NAD(P)H and was fully inhibited by Ogal. It was also inhibited by the proton uncoupler carbonylcyanide m chlorophenylhydrazone, suggesting the involvement of a chemiosmotic gradient. In addition, ATP synthesis was sensitive to 2,5-dibromo-3-methyl-6-isopropyl-p benzoquinone, a cytochrome b6f complex inhibitor. The possible participation of this complex in chromorespiration was supported by the detection of one of its components (cytochrome f) in chromoplasts using immunoblot and immunocytochemical techniques. The observed increased expression of cytochrome c6 during ripening suggests that it could act as electron acceptor of the cytochrome b6f complex in chromorespiration. The effects of Ogal on respiration and ATP levels were also studied in tissue samples. Oxygen uptake of mature green fruit and leaf tissues was not affected by Ogal, but was inhibited increasingly in fruit pericarp throughout ripening (up to 26% in red fruit). Similarly, Ogal caused a significant decrease in ATP content of red fruit pericarp. The number of energized mitochondria, as determined by confocal microscopy, strongly decreased in fruit tissue during ripening. Therefore, the contribution of chromoplasts to total fruit respiration appears to increase in late ripening stages. PMID- 25125505 TI - Beneficial effect of pistachio consumption on glucose metabolism, insulin resistance, inflammation, and related metabolic risk markers: a randomized clinical trial. AB - OBJECTIVE: To examine whether a pistachio-rich diet reduces the prediabetes stage and improves its metabolic risk profile. RESEARCH DESIGN AND METHODS: Prediabetic subjects were recruited to participate in this Spanish randomized clinical trial between 20 September 2011 and 4 February 2013. In a crossover manner, 54 subjects consumed two diets, each for 4 months: a pistachio-supplemented diet (PD) and a control diet (CD). A 2-week washout period separated study periods. Diets were isocaloric and matched for protein, fiber, and saturated fatty acids. A total of 55% of the CD calories came from carbohydrates and 30% from fat, whereas for the PD, these percentages were 50 and 35%, respectively (including 57 g/day of pistachios). RESULTS: Fasting glucose, insulin, and HOMA of insulin resistance decreased significantly after the PD compared with the CD. Other cardiometabolic risk markers such as fibrinogen, oxidized LDL, and platelet factor 4 significantly decreased under the PD compared with the CD (P < 0.05), whereas glucagon-like peptide-1 increased. Interleukin-6 mRNA and resistin gene expression decreased by 9 and 6%, respectively, in lymphocytes after the pistachio intervention (P < 0.05, for PD vs. CD). SLC2A4 expression increased by 69% in CD (P = 0.03, for PD vs. CD). Cellular glucose uptake by lymphocytes decreased by 78.78% during the PD (P = 0.01, PD vs. CD). CONCLUSIONS: Chronic pistachio consumption is emerging as a useful nutritional strategy for the prediabetic state. Data suggest that pistachios have a glucose- and insulin lowering effect, promote a healthier metabolic profile, and reverse certain metabolic deleterious consequences of prediabetes. PMID- 25125504 TI - Beyond the barrier: communication in the root through the endodermis. AB - The root endodermis is characterized by the Casparian strip and by the suberin lamellae, two hydrophobic barriers that restrict the free diffusion of molecules between the inner cell layers of the root and the outer environment. The presence of these barriers and the position of the endodermis between the inner and outer parts of the root require that communication between these two domains acts through the endodermis. Recent work on hormone signaling, propagation of calcium waves, and plant-fungal symbiosis has provided evidence in support of the hypothesis that the endodermis acts as a signaling center. The endodermis is also a unique mechanical barrier to organogenesis, which must be overcome through chemical and mechanical cross talk between cell layers to allow for development of new lateral organs while maintaining its barrier functions. In this review, we discuss recent findings regarding these two important aspects of the endodermis. PMID- 25125506 TI - Efficacy and safety of oral methazolamide in patients with type 2 diabetes: a 24 week, placebo-controlled, double-blind study. AB - OBJECTIVE: To evaluate the safety and efficacy of methazolamide as a potential therapy for type 2 diabetes. RESEARCH DESIGN AND METHODS: This double-blind, placebo-controlled study randomized 76 patients to oral methazolamide (40 mg b.i.d.) or placebo for 24 weeks. The primary efficacy end point for methazolamide treatment was a placebo-corrected reduction in HbA1c from baseline after 24 weeks (DeltaHbA1c). RESULTS: Mean +/- SD baseline HbA1c was 7.1 +/- 0.7% (54 +/- 5 mmol/mol; n = 37) and 7.4 +/- 0.6% (57 +/- 5 mmol/mol; n = 39) in the methazolamide and placebo groups, respectively. Methazolamide treatment was associated with a DeltaHbA1c of -0.39% (95% CI -0.82, 0.04; P < 0.05) (-4.3 mmol/mol [-9.0, 0.4]), an increase in the proportion of patients achieving HbA1c <=6.5% (48 mmol/mol) from 8 to 33%, a rapid reduction in alanine aminotransferase (~10 units/L), and weight loss (2%) in metformin-cotreated patients. CONCLUSIONS: Methazolamide is the archetype for a new intervention in type 2 diabetes with clinical benefits beyond glucose control. PMID- 25125507 TI - Brain iron overload, insulin resistance, and cognitive performance in obese subjects: a preliminary MRI case-control study. AB - OBJECTIVE: The linkage among the tissue iron stores, insulin resistance (IR), and cognition remains unclear in the obese population. We aimed to identify the factors that contribute to increased hepatic iron concentration (HIC) and brain iron overload (BIO), as evaluated by MRI, and to evaluate their impact on cognitive performance in obese and nonobese subjects. RESEARCH DESIGN AND METHODS: We prospectively recruited 23 middle-aged obese subjects without diabetes (13 women; age 50.4 +/- 7.7 years; BMI 43.7 +/- 4.48 kg/m2) and 20 healthy nonobese volunteers (10 women; age 48.8 +/- 9.5 years; BMI 24.3 +/- 3.54 kg/m2) in whom iron load was assessed in white and gray matter and the liver by MRI. IR was measured from HOMA-IR and an oral glucose tolerance test. A battery of neuropsychological tests was used to evaluate the cognitive performance. Multivariate regression analysis was used to identify the independent associations of BIO and cognitive performance. RESULTS: A significant increase in iron load was detected at the caudate nucleus (P < 0.001), lenticular nucleus (P = 0.004), hypothalamus (P = 0.002), hippocampus (P < 0.001), and liver (P < 0.001) in obese subjects. There was a positive correlation between HIC and BIO at caudate (r = 0.517, P < 0.001), hypothalamus (r = 0.396, P = 0.009), and hippocampus (r = 0.347, P < 0.023). The area under the curve of insulin was independently associated with BIO at the caudate (P = 0.001), hippocampus (P = 0.028), and HIC (P = 0.025). BIOs at the caudate (P = 0.028), hypothalamus (P = 0.006), and lenticular nucleus (P = 0.012) were independently associated with worse cognitive performance. CONCLUSIONS: Obesity and IR may contribute to increased HIC and BIO being associated with worse cognitive performance. BIO could be a potentially useful MRI biomarker for IR and obesity-associated cognitive dysfunction. PMID- 25125508 TI - Impact of a community health workers-led structured program on blood glucose control among latinos with type 2 diabetes: the DIALBEST trial. AB - OBJECTIVE: Latinos with type 2 diabetes (T2D) face major healthcare access and disease management disparities. We examined the impact of the Diabetes Among Latinos Best Practices Trial (DIALBEST), a community health worker (CHW)-led structured intervention for improving glycemic control among Latinos with T2D. RESEARCH DESIGN AND METHODS: A total of 211 adult Latinos with poorly controlled T2D were randomly assigned to a standard of healthcare (n = 106) or CHW (n = 105) group. The CHW intervention comprised 17 individual sessions delivered at home by CHWs over a 12-month period. Sessions addressed T2D complications, healthy lifestyles, nutrition, healthy food choices and diet for diabetes, blood glucose self-monitoring, and medication adherence. Demographic, socioeconomic, lifestyle, anthropometric, and biomarker (HbA1c, fasting blood glucose, and lipid profile) data were collected at baseline and 3, 6, 12, and 18 months (6 months postintervention). Groups were equivalent at baseline. RESULTS: Participants had high HbA1c at baseline (mean 9.58% [81.2 mmol/mol]). Relative to participants in the control group, CHWs had a positive impact on net HbA1c improvements at 3 months (-0.42% [-4.62 mmol/mol]), 6 months (-0.47% [-5.10 mmol/mol]), 12 months ( 0.57% [-6.18 mmol/mol]), and 18 months (-0.55% [-6.01 mmol/mol]). The overall repeated-measures group effect was statistically significant (mean difference 0.51% [-5.57 mmol/mol], 95% CI -0.83, -0.19% [-9.11, -2.03 mmol/mol], P = 0.002). CHWs had an overall significant effect on fasting glucose concentration that was more pronounced at the 12- and 18-month visits. There was no significant effect on blood lipid levels, hypertension, and weight. CONCLUSIONS: DIALBEST is an effective intervention for improving blood glucose control among Latinos with T2D. PMID- 25125511 TI - The role of non-governmental organizations in residential solid waste management: a case study of Puducherry, a coastal city of India. AB - Poorly planned and uncontrolled urbanization in India has caused a variety of negative, often irreversible, environmental impacts. The impacts appear to be unavoidable and not easily mitigable due to the mounting public health problems caused by non-segregation of solid wastes at source and their subsequent improper management. Recently in India, non-governmental organizations (NGOs) and other civil society organizations have increasingly started to get involved in improving waste management services. Municipal solid waste management being a governmental function, the contribution of NGOs in this field has not been well documented. This study highlights the activities and services of Shuddham, an NGO functioning in the town of Puducherry within the Union Territory of Puducherry in South India. The NGO program promoted much needed awareness and education, encouraged source separation, enhanced door-to-door collection, utilized wastes as raw materials and generated more job opportunities. Even though source separation prior to door-to-door collection is a relatively new concept, a significant percentage of residents (39%) in the study area participated fully, while a further 48% participated in the collection service. The average amount of municipal solid waste generated by residential units in the Raj Bhavan ward was 8582 kg/month of which 47% was recovered through active recycling and composting practices. The study describes the features and performance of NGO-mediated solid waste management, and evaluates the strengths and weaknesses as well as the opportunities and threats of this system to see whether this model can sustainably replace the low-performance conventional solid waste management in practice in the town of Puducherry. The experiences from this case study are expected to provide broad guidelines to better understand the role of NGOs and their contributions towards sustainable waste management practices in urban areas. PMID- 25125510 TI - Enhancing biogas production from anaerobic biodegradation of the organic fraction of municipal solid waste through leachate blending and recirculation. AB - Leachate recirculation has a profound advantage on biodegradation of the organic fraction of municipal solid waste in landfills. Mature leachate from older sections of landfills (>10 years) and young leachate were blended and added to organic fraction of municipal solid waste in a series of biomethane potential assay experiments with different mixing ratios of mature and young leachate and their effect on biogas production was monitored. The improvement in biogas production was in the range of 19%-41% depending on the ratio of mixing old and new leachate. The results are conclusive that the biogas generation could be improved by blending the old and new leachate in a bioreactor landfill system as compared with a conventional system employed in bioreactor landfills today for recirculating the same age leachate. PMID- 25125512 TI - Calcaneal "Z" osteotomy effect on hindfoot varus after triple arthrodesis in a cadaver model. AB - BACKGROUND: Triple arthrodesis involves subtalar, talonavicular, and calcaneocuboid joint fusion and is performed to relieve pain and correct deformity. Complications include malunion resulting in equinovarus and lateral column overload, which can lead to painful callosities and stress fractures. This study quantified the effectiveness of a closing-wedge calcaneal "Z" osteotomy for correction of the varus condition and reduction of abnormal loading of the lateral border of the foot. METHODS: Ten fresh-frozen feet were used. Angle meters were attached to the calcaneus and second cuneiform to measure hindfoot and midfoot varus, and pressure sensors were placed under the first and fifth metatarsal heads to document loading of the borders of the foot. Tensile loads were applied to ten extrinsic tendons and the Achilles tendon while an 1187 N axial foot load was applied. Calcaneus and second cuneiform coronal plane angles and medial and lateral plantar pressures were measured initially, after triple fusion-induced varus, and after "Z" osteotomy. RESULTS: The calcaneal "Z" osteotomy had no significant corrective effect, with hindfoot alignment virtually identical before and after the procedure under the described foot loading conditions. Similarly, second cuneiform inclination, representative of midfoot alignment, showed no change from the osteotomy. Medial and lateral peak plantar pressures after calcaneal "Z" osteotomy did not differ from those measured after varus triple fusion. CONCLUSION: In this cadaver model of varus malunited triple arthrodesis, the closing-wedge calcaneal "Z" osteotomy was ineffective for correction of bone alignment and lateral forefoot overloading under the tested conditions. CLINICAL RELEVANCE: The results provide additional information on which to base treatment after triple arthrodesis with varus malunion. PMID- 25125513 TI - Comparison of nonlocking plates and locking plates for intraarticular calcaneal fracture. AB - BACKGROUND: The optimal treatment of displaced intraarticular calcaneal fractures remains challenging. Currently, there is no uniform method to treat such fractures. The purpose of this study was to compare the radiographic and clinical outcome of nonlocking plates and locking plates in the treatment of intraarticular calcaneal fractures. METHODS: A retrospective comparative study was performed including 42 patients with intraarticular calcaneal fractures that were treated by nonlocking plate (n = 18) or locking plates (n = 24) between January 2010 and June 2012. Radiological and functional outcomes were compared between the 2 groups. RESULTS: At the final follow-up, all fractures were healed, and the patients with a locking plate had a significantly better Bohler's angle and Gissane's angle compared with the nonlocking plate group (P < .05). No complications occurred for the patients in the locking plate group, and 3 patients in the nonlocking plate group had implant loosening that led to loss of reduction (P < .05). The average American Orthopaedic Foot and Ankle Society hindfoot score in the locking plate group was significantly higher than that in the nonlocking plate group (P < .05). No statistically significant difference between the 2 groups was found regarding SF-36 (P > .05). CONCLUSION: This study supports the view that locking plates may provide better stability and functional recovery in the treatment of intraarticular calcaneal fractures. LEVEL OF EVIDENCE: Level III, comparative case series. PMID- 25125509 TI - Molecular architecture of mammalian nitric oxide synthases. AB - NOSs are homodimeric multidomain enzymes responsible for producing NO. In mammals, NO acts as an intercellular messenger in a variety of signaling reactions, as well as a cytotoxin in the innate immune response. Mammals possess three NOS isoforms--inducible, endothelial, and neuronal NOS--that are composed of an N-terminal oxidase domain and a C-terminal reductase domain. Calmodulin (CaM) activates NO synthesis by binding to the helical region connecting these two domains. Although crystal structures of isolated domains have been reported, no structure is available for full-length NOS. We used high-throughput single particle EM to obtain the structures and higher-order domain organization of all three NOS holoenzymes. The structures of inducible, endothelial, and neuronal NOS with and without CaM bound are similar, consisting of a dimerized oxidase domain flanked by two separated reductase domains. NOS isoforms adopt many conformations enabled by three flexible linkers. These conformations represent snapshots of the continuous electron transfer pathway from the reductase domain to the oxidase domain, which reveal that only a single reductase domain participates in electron transfer at a time, and that CaM activates NOS by constraining rotational motions and by directly binding to the oxidase domain. Direct visualization of these large conformational changes induced during electron transfer provides significant insight into the molecular underpinnings governing NO formation. PMID- 25125515 TI - European Restart a Heart Day. PMID- 25125514 TI - Transdermal glyceryl trinitrate in the treatment of ischemia following toe deformity correction: a case series. PMID- 25125517 TI - Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary . BET 1: Do patients with an asymptomatic sub-segmental pulmonary embolism need anticoagulation therapy? AB - A short cut review was carried out to establish whether therapeutic anticoagulation is required for patients who have an incidental diagnosis of subsegmental pulmonary embolism (PE), which is asymptomatic. 4 studies were relevant to the three-part question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The evidence suggests that patients with clinically unsuspected PE may have better prognostic outcomes than those with symptomatic presentations, especially if the PE is at the sub-segmental level. The only direct comparison of anti-coagulation versus no anti-coagulation in patients with an asymptomatic, unsuspected PE suggests a survival benefit from anti-coagulation. However, this study included patients with cancer and was not restricted to patients with subsegmental PE. Consequently, the clinical bottom line is that level 1 evidence is required to answer this question. In the meantime decisions must continue to be informed by clinical judgment. PMID- 25125516 TI - Chinese bystanders in medical emergencies: apathetic or bewildered? PMID- 25125519 TI - Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: the use of local anaesthetic lubrication for the catheterisation of males. AB - A short cut review was carried out to establish whether local anaesthetic lubrication is necessary for urethral catheterisation in men. Two studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that the use of local anaesthetic is effective in this population and should form part of the procedure. PMID- 25125551 TI - Moving the worksite health promotion profession forward: is the time right for requiring standards? A review of the literature. AB - Standards in any profession are adopted to assure that the individuals hired are adequately trained and the programs that they oversee are of the highest quality. Worksite health promotion should be no different from any other field. A review of the research conducted by experts in worksite health promotion is examined, along with an assessment of skills needed to ensure that wellness programs are effective and employees, their families, and even their communities are educated on the ways to best prevent chronic diseases and occupational incidences through healthy and safe behaviors. This article is consistent with Health Promotion Practice's mission and focuses on the exploration of the processes used to plan effective worksite health promotion programs, and it suggests initial discussions on whether these processes should become standards for professionals in the worksite health promotion field. PMID- 25125552 TI - When 4.5 million people become patients. PMID- 25125553 TI - Relvar Ellipta for asthma. AB - ?Relvar Ellipta (GSK) is a dry powder inhaler that contains a corticosteroid (fluticasone furoate) and a long-acting beta2 agonist (vilanterol trifenatate). It is licensed for once-daily use as maintenance therapy for chronic obstructive pulmonary disease (COPD) and asthma. In a previous article we considered its use in the management of COPD.1 Here we review the evidence for Relvar Ellipta in the treatment of patients with asthma. PMID- 25125554 TI - 'Evolution-proofing' antibacterials. PMID- 25125556 TI - Any detectable thyroglobulin in lymph node biopsy washouts suggests local recurrence in differentiated thyroid cancer. AB - The sensitivity of local recurrence detection in differentiated thyroid cancer (DTC) is increased by measuring thyroglobulin in needle washouts from lymph node fine-needle aspiration biopsies (FNA-Tg). Recent studies have proposed minimum diagnostic threshold values for FNA-Tg and have reported interference from Tg antibodies (Tg Ab), leading to low or false-negative results. The aim of this study was to assess the utility of FNA-Tg in the diagnosis of local DTC recurrence in patients referred to a single pathology service used by our tertiary teaching hospital, the first such study in an Australian cohort. Data were collected from the pathology service database for FNA-Tg over an 18-month period, and the results of 69 FNA-Tg samples from 57 patients were obtained. FNA Tg findings were compared with cytology and histology when patients proceeded to surgery. Using the functional sensitivity as the cut-off, detectable FNA-Tg (>=0.9 MUg/l) had a sensitivity of 95.7%, specificity of 50% and positive predictive value of 95.7%. Our results suggest that detectable FNA-Tg leads to histological confirmation of local nodal DTC recurrence and would support a decision to proceed to surgery. Serum Tg Ab can, however, interfere with FNA-Tg measurements. Thus, we now recommend routine use of FNA-Tg washouts in all lymph node FNA biopsies for the detection of DTC recurrence. PMID- 25125555 TI - Management of insulin pump therapy in children with type 1 diabetes. AB - Insulin pump therapy is a current treatment option for children and adolescents with type 1 diabetes. Insulin pumps can provide a greater flexibility in insulin administration and meal planning, as compared with multiple insulin injections, and they may be particularly suitable for the paediatric age group. Many young people with diabetes have integrated insulin pumps into their daily practice. The use of insulin pumps can also be supplemented by the information retrieved from continuous glucose monitoring in the sensor-augmented pump therapy, which may improve glycaemic control. In this review, we describe the principles of pump therapy and summarise features of commercially available insulin pumps, with focus on practical management and the advantages and disadvantages of this technology. PMID- 25125557 TI - Corticosterone metabolites in laying hen droppings-Effects of fiber enrichment, genotype, and daily variations. AB - There is growing interest and concern for animal welfare in commercial poultry production. To evaluate stress and welfare in an objective and noninvasive way, fecal corticosterone metabolites (FCM) in droppings can be analyzed. However, the influence of diet, genotype, and daily variations in FCM and production of droppings in laying hens has been poorly investigated. This study examined the effect of insoluble fiber by adding 3% ground straw pellets to the feed to Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB) hens housed in furnished cages between 20 and 40 wk of age. In total, 960 hens were included in the study. Droppings were collected 4 times per day for 3 consecutive days and analyzed by corticosterone immunoassay. Biological validation confirmed the ability of the assay to detect changes in FCM levels. Inclusion of straw pellets in the feed increased FCM concentration in both hen genotypes and increased excretion rate of FCM in LB hens. The LB hens also produced greater amounts of droppings than LSL hens. Both FCM levels and production of droppings varied during the day, although no distinct diurnal rhythm was found. These findings demonstrate that when using FCM to evaluate stress and welfare in laying hens, many factors (e.g., diet, genotype used, and so on) need to be taken into account to allow accurate interpretation of the results. In addition, under certain conditions, excretion rate of FCM might be more appropriate to use compared with FCM concentration. PMID- 25125558 TI - The effect of perch availability during pullet rearing and egg laying on the behavior of caged White Leghorn hens. AB - Enriched cages, compared with conventional cages, allow egg laying strains of chickens to meet some behavioral needs, including a high motivation to perch. The objective of this study was to determine if perch availability during rearing affected perch use as adults and if perch presence affected eating and drinking in caged White Leghorn hens. Chickens were assigned to 14 cages each with and without 2 round metal perches from hatch to 16.9 wk of age. At 17 wk of age, pullets were assigned to laying cages consisting of 1 of 4 treatments. Treatment 1 chickens never had access to perches (controls). Treatment 2 chickens only had access to 2 round metal perches during the laying phase (17 to 71 wk of age). Treatment 3 chickens only had access to 2 round perches during the pullet phase (0 to 16.9 wk of age). Treatment 4 chickens had access to the perches during both the pullet and laying phase. Each treatment during the adult phase consisted of 9 cages with 9 birds/cage for a total of 36 cages. Automatic infrared cameras were used to monitor behavior of hens in each cage for a 24-h period at 19, 24, 29, 34, 39, 44, 49, 54, 59, 64, and 69 wk of age. Behavior was also recorded twice weekly by an observer in the room where the hens were housed during photophase from 25 to 68 wk of age. Behavioral data were analyzed using ANOVA with repeated measures and the MIXED model procedure. A greater proportion of hens without perches as pullets used the rear perch more during both photophase and scotophase than hens with prior pullet perching experience. Eating and drinking activities of caged adult Leghorns were not impaired by their prior experience to perches as pullets or by the presence of perches in laying cages. It is concluded that providing perches in cages to White Leghorns during pullet rearing did not facilitate use of perches as adults. PMID- 25125559 TI - Enhanced immune responses of chickens to oral vaccination against infectious bursal disease by ginseng stem-leaf saponins. AB - Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), is an immunosuppressive infectious disease of global economic importance in poultry. This study was designed to evaluate the effect of oral administration of ginseng stem-leaf saponins (GSLS) on humoral and gut mucosal immunity in chickens vaccinated with live IBDV vaccine, and furthermore, to test its protective efficacy against virulent IBDV challenge following vaccination. In experiment 1, chickens were orally administered with GSLS at 5 mg/kg of BW for 7 d, and then immunized with live IBDV vaccine via the oral route. Serum was sampled on 0, 1, 2, 3, 4, and 5 wk postvaccination for detecting antibody titers by ELISA, and intestinal tissues were collected on 0, 1, 3, and 5 wk postvaccination for measurement of IgA-positive cells and intestinal intraepithelial lymphocytes by immunohistochemical and hematoxylin-eosin staining, respectively. Result showed that antibody titers, IgA-positive cells and intestinal intraepithelial lymphocytes were significantly higher in chickens drinking GSLS than the control, suggesting an enhanced effect of GSLS on humoral and gut mucosal immune responses. In experiment 2, chickens were delivered with GSLS and then vaccinated in the same way as in experiment 1. The birds were challenged with virulent IBDV at wk 3 postvaccination. Then the birds were weighed, bled, and necropsied at d 3 postchallenge and the bursae were sampled for gross and histopathological examination. Results demonstrated that GSLS provided a better protection against virulent IBDV challenge following vaccination than the control. In conclusion, oral administration of GSLS enhances both humoral and gut mucosal immune responses to IBDV and offers a better protection against virulent IBDV challenge. Considering its immunomodulatory properties to IBDV vaccine, GSLS might be a promising oral adjuvant for vaccination against infectious diseases in poultry. PMID- 25125560 TI - Nutrient analysis, metabolizable energy, and digestible amino acids of soybean meals of different origins for broilers. AB - Nutrient composition, ileal amino acid (AA) digestibility, and AME of 55 soybean meal (SBM) samples from the United States (US; n = 16), Argentina (ARG; n = 16), Brazil (BRA; n = 10), and India (IND; n = 13), collected from commercial mills in Southeast Asia, were compared using laboratory analyses and animal studies. There were significant (P < 0.05 to 0.001) differences due to origin in CP, fat, ash, fiber, and nonstarch polysaccharide (NSP) contents of SBM. The average CP content of US, ARG, BRA, and IND samples was determined to be 47.3, 46.9, 48.2, and 46.4% (as-fed basis), respectively. Compared with SBM from other origins, crude fiber and NSP contents were lower (P < 0.05) and sucrose content was higher (P < 0.05) in the US samples. The IND samples had the highest (P < 0.05) contents of fiber, ash, and NSP, and lowest (P < 0.05) contents of fat and sucrose. Differences (P < 0.0001) were observed among origins for in vitro protein quality measures (urease index, KOH protein solubility, and trypsin inhibitor activity). Significant (P < 0.001) effects due to origin were observed for all minerals. Soybean meal from the US and IND had higher (P < 0.05) calcium contents (0.45%) compared with those from ARG and BRA (0.28-0.31%). Phosphorus and potassium contents were lowest (P < 0.05) in SBM from IND, and no differences (P > 0.05) were observed in SBM from other origins. Iron content was markedly high (928 mg/kg) in SBM from IND compared with those from other origins (103-134 mg/kg). Major origin-related differences (P < 0.0001) were observed in the AME of SBM. The average AME content of US, ARG, BRA, and IND samples was 2,375, 2,227, 2,317, and 2,000 kcal/kg (as fed basis), respectively. Total AA contents of US, ARG, BRA, and IND samples were similar (P > 0.05) for 9 of the 17 amino acids. Major differences (P < 0.05 to P < 0.001) due to origin were determined for the digestibility of all AA. The IND samples had the lowest (P < 0.05) digestibility and no differences (P > 0.05) between samples from other 3 origins. However, the digestible CP content of US SBM was higher (P < 0.05) than those of ARG and IND, but similar (P > 0.05) to that from BRA. The digestible CP contents of SBM from the US, ARG, BRA, and IND were 40.0, 38.6, 39.8, and 36.7%, respectively. Digestible contents of indispensable AA, in general, followed the same trend as that of digestible CP. In conclusion, the present evaluation showed that major differences in nutritive value do exist between SBM from different origins in terms of nutrient contents, AME, and digestible AA. Overall, SBM originating from the US had better nutritive value compared with those from ARG and IND, on the basis of AME and contents of digestible CP and digestible AA. PMID- 25125561 TI - Effects of alkaline concentration, temperature, and additives on the strength of alkaline-induced egg white gel. AB - Egg whites can undergo gelation at extreme pH. In this paper, the effects of NaOH concentration (1.5, 2, 2.5, and 3%), temperature (10, 20, 30, and 40 degrees C), and additives (metallic compounds, carbohydrates, stabilizers, and coagulants) on the strength of alkaline-induced egg white gel were investigated. Results showed that NaOH concentration and induced temperature significantly affected the rate of formation and peak strength of the egg white gel. Of the 6 metallic compounds used in this experiment, CuSO4exhibited the optimal effect on the strength of alkaline-induced egg white gel, followed by MgCl2, ZnSO4, PbO, and CaCl2. When CuSO4concentration was 0.2%, the gel strength increased by 31.92%. The effect of Fe2(SO4)3was negligible. Of the 5 carbohydrate additives, xanthan gum (0.2%) caused the highest increase (54.31%) in the strength of alkaline-induced egg white gel, followed by sodium alginate, glucose, starch, and sucrose. Meanwhile, propylene glycol (0.25%) caused the highest improvement (15.78%) in the strength of alkaline-induced egg white gel among the 3 stabilizing agents and coagulants used, followed by Na2HPO4and glucono-delta-lactone. PMID- 25125562 TI - Neopterin and biopterin as biomarkers of immune system activity associated with crating in broiler chickens. AB - Neopterin and biopterin belong to a group of unconjugated pterin derivates. These biomolecules are present in many animal species and perform several functions. Pterin concentrations may provide additional information on the effect of stress on immune system activity. This study focused on an investigation of the effect of crating on plasma concentrations of neopterin and biopterin in broilers. The effects of 2 crating periods (2 and 4 h) were monitored in Hubbard broilers (n = 90) aged 42 d. After a given crating period, randomly selected chickens from each group were sampled immediately and the remaining chickens were sampled after 24 h. Plasma corticosterone increased (P < 0.001) immediately after 2 and 4 h crating, but no difference between the crated and the control noncrated broilers was found 24 h later. Immediately after crating, neopterin in 2- and 4-h broilers did not differ from the control, but 24 h later a decrease (P = 0.011) in plasma neopterin was found in 4-h broilers compared with the control. Simultaneously, 24 h after crating, neopterin levels in 2- and 4-h broilers decreased (P < 0.001) in comparison with the levels immediately after crating. Plasma biopterin was higher (P < 0.001) in 4-h broilers than in the control immediately after the crating. A time of sampling effect (P = 0.016) was found for the heterophil-to-lymphocyte ratio, with heterophil-to-lymphocyte ratio higher 24 h after crating in comparison with its level immediately after the crating. This study shows that crating may significantly affect the immune system of broiler chickens. This is corroborated by the increase in plasma biopterin concentrations in broilers immediately after crating and the decrease in plasma neopterin concentrations in broilers 24 h after crating. The correlations were found for widely used indicators of acute and chronic stress in birds [i.e., plasma corticosterone concentrations (biopterin) and the heterophil-to-lymphocyte ratio (neopterin), respectively]. PMID- 25125563 TI - Single nucleotide polymorphism variants within tva and tvb receptor genes in Chinese chickens. AB - Avian leukosis is an immunosuppressive neoplastic disease caused by avian leukosis viruses (ALV), which causes tremendous economic losses in the worldwide poultry industry. The susceptibility or resistance of chicken cells to subgroup A ALV and subgroup B, D, and E ALV are determined by the receptor genes tumor virus locus A (tva) and tumor virus locus B (tvb), respectively. Four genetic resistant loci (tva(r1), tva(r2), tva(r3), and tva(r4)) in tva receptor gene and a genetic resistant locus tvb(r) in the tvb receptor gene have been identified in inbred lines of White Leghorn. To evaluate the genetic resistance to subgroup A, B, D, and E ALV, genetic variations within resistant loci in tva and tvb genes were screened in Chinese local chicken breeds and commercial broiler lines. Here, the heterozygote tva(s1/r1) and the resistant genotype tva(r2/r2), tva(r3/r3), and tva(r4/r4) were detected in Chinese chickens by direct sequencing. The heterozygote tva(s1/r1) was detected in Huiyang Bearded chicken (HYBC), Rizhaoma chicken, and commercial broiler line 13 to 15 (CB13 to CB15), with the frequencies at 0.08, 0.18, 0.17, 0.25, and 0.15, respectively. The resistant genotype tva(r2/r2) was detected in Jiningbairi chicken (JNBRC), HYBC, and CB15, with the frequencies at 0.03, 0.08, and 0.06, respectively, whereas tva(r3/r3) and tva(r4/r4) were detected in 19 and 17 of the 25 Chinese chickens tested, with the average frequencies at 0.13 and 0.20, respectively. Furthermore, the resistant genotype tvb(r/r) was detected in JNBRC, CB07, CB12, CB14, and CB15 by pyrosequencing assay, with the frequencies at 0.03, 0.03, 0.11, 0.09, and 0.15, respectively. These results demonstrated that the potential for genetic improvement of resistance to subgroup A, B, D, and E ALV were great both in Chinese local chickens and commercial broilers. This study provides valuable insight into the selective breeding for chickens genetically resistant to ALV. PMID- 25125564 TI - Urea cycle disorders: a life-threatening yet treatable cause of metabolic encephalopathy in adults. AB - Urea cycle disorders are inborn errors of metabolism that, in rare cases, can present for the first time in adulthood. We report a perplexing presentation in a woman 4 days postpartum of bizarre and out-of-character behaviour interspersed with periods of complete normality. Without any focal neurological signs or abnormality on initial investigations, the diagnosis became clear with the finding of a significantly elevated plasma ammonia level, just as she began to deteriorate rapidly. She improved following intravenous dextrose and lipid emulsion, together with sodium benzoate, arginine and a protein-restricted diet. She remains well 12 months later with no permanent sequelae. Whilst this is a rare presentation of an uncommon disease, it is a treatable disorder and its early diagnosis can prevent a fatal outcome. PMID- 25125565 TI - HIV-1 clinical isolates with the E138A substitution in reverse transcriptase show full susceptibility to emtricitabine and other nucleoside reverse transcriptase inhibitors. PMID- 25125567 TI - eComment. Experimental controversy regarding the role of adipose-derived stem cells in surgical oncology. PMID- 25125568 TI - eComment. Underestimated occurrence of mesenteric ischaemia after cardiac surgery. PMID- 25125570 TI - Sustained ventricular tachycardia and coved-type electrocardiogram in peripheral leads: a particularly malignant phenotype of Brugada syndrome? PMID- 25125571 TI - Endocardial left ventricular lead placement from the left subclavian vein approach. AB - AIMS: In up to 10-15% of cases, the traditional epicardial approach for left ventricular (LV) lead placement is not feasible and surgical implantation is considered the alternative. We present the implantation of a transseptal LV lead through a left subclavian access. METHODS AND RESULTS: Through the left subclavian vein access and using a system which includes a guiding catheter, a puncture screw catheter and a puncture stylet, access to the LV was achieved and the LV stimulation lead was successfully implanted. CONCLUSION: We describe the implantation of a transseptal LV stimulation lead through a left subclavian access. PMID- 25125572 TI - Unsuitability of the epidemiological approach to bicycle transportation injuries and traffic engineering problems. AB - Bicyclists and transportation professionals would do better to decline advice drawn from characteristically epidemiological studies. The faults of epidemiology are both accidental (unpreparedness for the task) and essential (unsuitability of the methods). Characteristically epidemiological methods are known to be error prone, and when applied to bicycle transportation suffer from diversion bias, inappropriately broad-brush categorisations, a focus on undifferentiated risk rather than on danger, a bias towards unsafe behaviour, and an overly narrow perspective. To the extent that there is a role for characteristically epidemiological methods, it should be the same as anywhere else: as a preliminary or adjunct to the scientific method, for which there is no substitute. PMID- 25125573 TI - Signalling at tight junctions during epithelial differentiation and microbial pathogenesis. AB - Tight junctions are a component of the epithelial junctional complex, and they form the paracellular diffusion barrier that enables epithelial cells to create cellular sheets that separate compartments with different compositions. The assembly and function of tight junctions are intimately linked to the actomyosin cytoskeleton and, hence, are under the control of signalling mechanisms that regulate cytoskeletal dynamics. Tight junctions not only receive signals that guide their assembly and function, but transmit information to the cell interior to regulate cell proliferation, migration and survival. As a crucial component of the epithelial barrier, they are often targeted by pathogenic viruses and bacteria, aiding infection and the development of disease. In this Commentary, we review recent progress in the understanding of the molecular signalling mechanisms that drive junction assembly and function, and the signalling processes by which tight junctions regulate cell behaviour and survival. We also discuss the way in which junctional components are exploited by pathogenic viruses and bacteria, and how this might affect junctional signalling mechanisms. PMID- 25125574 TI - Thinness in the era of obesity: trends in children and adolescents in The Netherlands since 1980. AB - BACKGROUND: Although children both at the upper and lower tail of the body mass index (BMI) distribution are at greater health risk, relatively little is known about the development of thinness prevalence rates in developed countries over time. We studied trends in childhood thinness and assessed changes in the BMI distribution since the onset of the obesity epidemic. METHODS: Growth data from 54 814 children aged 2-18 years of Dutch, Turkish and Moroccan origin living in The Netherlands were used. Anthropometric measurements were performed during nationwide cross-sectional growth studies in 1980 (only Dutch), 1997 and 2009. Prevalence rates of thinness grades I, II and III were calculated according to international cut-offs. BMI distributions for 1980, 1997 and 2009 were compared. RESULTS: Since 1980, thinness (all grades combined) reduced significantly from 14.0% to 9.8% in children of Dutch origin, but the proportion of extremely thin children (grade III) remained constant. Thinness in children of Moroccan origin decreased significantly from 8.8% to 6.2% between 1997 and 2009. No significant difference was observed in children of Turkish origin (5.4% in 1997 vs. 5.7% in 2009). Thinness occurred most often in children aged 2-5 years. There were no differences between boys and girls. The BMI distribution widened since 1980, mainly due to an upward shift of the upper centiles. CONCLUSION: Since the onset of the obesity epidemic, prevalence rates of thinness decreased. However, we found a small but persistent group of extremely thin children. More research is needed to gain insight into their health status. PMID- 25125575 TI - 'By failing to prepare you are preparing to fail': lessons from the 2009 H1N1 'swine flu' pandemic. AB - BACKGROUND: Pandemic influenza has the potential to cause widespread death and destruction. Communications with the public have a vital role in the prevention of pandemic influenza by promoting the effective uptake of behaviours that can delay the spread of infection. This study explored the development and implementation of communications in the pandemic influenza outbreak of H1N1 ('swine flu') in 2009 in three European countries. METHODS: In-depth interviews were conducted with senior policy and communication officials involved in the planning and delivery of communications programmes in England, Italy and Hungary. RESULTS: The study found a lack of planning and a low value attached to the skills required to produce effective communications. In all case study countries there was a dearth of good quality audience research to inform the development of communications. Little thought had been given to the tone, targeting or channelling of messages. Instead, communications were characterized by a 'one size fits all' and a 'top down', expert-led response. There was also little effort to evaluate the impact of communications, but where this was done, very low levels of public compliance and engagement with key behavioural messages were found. CONCLUSIONS: Policy makers should prioritize investment in the skills and expertise required to achieve desired behaviour changes. Audience research should be conducted throughout the planning cycle to inform national communications strategies. This should include insights to inform the segmentation of public audiences, targeting of messages and consideration of content and emotional tone most likely to achieve desired behavioural outcomes. PMID- 25125576 TI - Mapping the denominator: spatial demography in the measurement of progress. AB - Measuring progress towards international health goals requires a reliable baseline from which to measure change and recent methodological advancements have advanced our abilities to measure, model and map the prevalence of health issues using sophisticated tools. The provision of burden estimates generally requires linking these estimates with spatial demographic data, but for many resource-poor countries data on total population sizes, distributions, compositions and temporal trends are lacking, prompting a reliance on uncertain estimates. Modern technologies and data archives are offering solutions, but the huge range of uncertainties that exist today in spatial denominator datasets will still be around for many years to come. PMID- 25125577 TI - 'A living death': a qualitative assessment of quality of life among women with trichiasis in rural Niger. AB - BACKGROUND: Prior to blindness, trachoma is thought to profoundly affect women's abilities to lead normal lives, but supporting evidence is lacking. To better understand the effects of trichiasis, we asked women to define quality of life, how trichiasis affects this idea and their perceptions of eyelid surgery. METHODS: Operated and unoperated women were purposively selected for in-depth interviews. These were audio-recorded and transcribed, and codes were identified and applied to the transcripts. Overarching themes, commonalities and differences were identified and matched to quotations. RESULTS: Twenty-three women were interviewed. Quality of life was defined as health, security, family, social status and religious participation. Trichiasis caused severe pain and loss of health, leading to loss of security. This affected social, economic and religious activities and caused burden on their families. Surgery improved quality of life, even in cases of surgical failure or recurrent disease. CONCLUSIONS: Trichiasis disables most women, even those reporting fewer or less-severe symptoms. While women in rural Niger often live in extreme poverty, trichiasis exacerbates the situation, making women unable to work and undermining their social status. It adds to family burden, as women lose the ability to meaningfully contribute to the household and require additional family resources for their care. PMID- 25125578 TI - Factors associated with physical therapists' implementation of physical activity interventions in The Netherlands. AB - BACKGROUND: Physical therapists play an important role in the promotion of physical activity (PA) and the effectiveness of PA interventions. However, little is known about the extent to which they implement PA interventions following the intervention protocol and about the factors influencing their implementation behaviors. OBJECTIVE: The study objective was to investigate physical therapists' implementation fidelity regarding PA interventions, including completeness and quality of delivery, and influencing factors with a Theoretical Domains Framework based questionnaire. DESIGN: The study was based on a cross-sectional design. METHODS: A total of 268 physical therapists completed the Determinants of Implementation Behavior Questionnaire. Questions about completeness and quality of delivery were based on components and tasks of PA interventions as described by the Royal Dutch Society for Physical Therapy. Multilevel regression analyses were used to identify factors associated with completeness and quality of delivery. RESULTS: High implementation fidelity was found for the physical therapists, with higher scores for completeness of delivery than for quality of delivery. Physical therapists' knowledge, skills, beliefs about capabilities and consequences, positive emotions, behavioral regulation, and the automaticity of PA intervention delivery were the most important predictors of implementation fidelity. Together, the Theoretical Domains Framework accounted for 23% of the variance in both total completeness and total quality scores. LIMITATIONS: The cross-sectional design precluded the determination of causal relationships. Also, the use of a self-report measure to assess implementation fidelity could have led to socially desirable responses, possibly resulting in more favorable ratings for completeness and quality. CONCLUSIONS: This study enhances the understanding of how physical therapists implement PA interventions and which factors influence their behaviors. Knowledge about these factors may assist in the development of strategies to improve physical therapists' implementation behaviors. PMID- 25125580 TI - Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans. AB - The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3 [(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia. PMID- 25125579 TI - Anaplerotic metabolism of alloreactive T cells provides a metabolic approach to treat graft-versus-host disease. AB - T-cell activation requires increased ATP and biosynthesis to support proliferation and effector function. Most models of T-cell activation are based on in vitro culture systems and posit that aerobic glycolysis is employed to meet increased energetic and biosynthetic demands. By contrast, T cells activated in vivo by alloantigens in graft-versus-host disease (GVHD) increase mitochondrial oxygen consumption, fatty acid uptake, and oxidation, with small increases of glucose uptake and aerobic glycolysis. Here we show that these differences are not a consequence of alloactivation, because T cells activated in vitro either in a mixed lymphocyte reaction to the same alloantigens used in vivo or with agonistic anti-CD3/anti-CD28 antibodies increased aerobic glycolysis. Using targeted metabolic (13)C tracer fate associations, we elucidated the metabolic pathway(s) employed by alloreactive T cells in vivo that support this phenotype. We find that glutamine (Gln)-dependent tricarboxylic acid cycle anaplerosis is increased in alloreactive T cells and that Gln carbon contributes to ribose biosynthesis. Pharmacological modulation of oxidative phosphorylation rapidly reduces anaplerosis in alloreactive T cells and improves GVHD. On the basis of these data, we propose a model of T-cell metabolism that is relevant to activated lymphocytes in vivo, with implications for the discovery of new drugs for immune disorders. PMID- 25125581 TI - Commentary: Does mortality from smoking have implications for future Mendelian randomization studies? PMID- 25125582 TI - Auditing documentation on delivery room management using video and physiological recordings. AB - OBJECTIVE: Neonatal resuscitation is often retrospectively documented, which can lead to inaccuracy and incomplete recording of delivery room management. In this study, we assessed the accuracy and completeness of neonatal resuscitation documentation in our neonatal intensive care unit. METHODS: Recordings of physiological parameters and video data were performed in the delivery room and used to deduct the clinical condition of the infant, the interventions done and their effect on the infant's condition. The data from the recordings were compared with the documentation on neonatal stabilisation in the medical records (paper or digital). RESULTS: Recordings of 54 infants were compared with the documentation in their medical records. In 93% of the medical records delivery room management was documented. The clinical condition of the infant at birth was documented in 76% and 1 min Apgar scores in 98%. Respiratory support was correctly documented in 83%, heart rate in 37% and oxygen saturation in 13%. In 57% use of supplemental oxygen and its indication were correctly reported. Seven infants were intubated and this was correctly documented in 57%. Apgar scores were compared between the recordings and the medical records. At 1 min, 5 min and 10 min after birth the Apgar score, given by the researcher using the recordings, was similar to the scores in the medical records in 33%, 44% and 53%, respectively. CONCLUSIONS: Accurate and complete documentation of neonatal resuscitation continues to be a challenge. Recordings of physiological parameters and video imaging can improve documentation by providing detailed information. PMID- 25125583 TI - Brain. Editorial. PMID- 25125584 TI - 'Idiopathic' no more! Abnormal interaction of large-scale brain networks in generalized epilepsy. PMID- 25125585 TI - Hereditary dystonia and parkinsonism: two sides of the same coin? PMID- 25125586 TI - Neuronal substrate of cognitive impairment in post-stroke dementia. PMID- 25125587 TI - The next step in modern brain lesion analysis: multivariate pattern analysis. PMID- 25125588 TI - Psoriatic arthritis: current therapy and future approaches. AB - PsA is a systemic inflammatory condition that affects 20-30% of patients with psoriasis. It is characterized by potential involvement of diverse tissues, including peripheral and axial joints, enthesitis, dactylitis and skin and nail disease. The degree of involvement in each domain can vary over time in individual patients and can differ substantially between PsA patients. The clinical heterogeneity along with the varying extent of severity and activity can pose significant challenges to treatment. Although some studies had suggested immunopathophysiological similarities between PsA and RA, more recently important distinctions have been defined. Similarly, although some immunomodulatory therapies have proved effective for both PsA and RA, recent data suggest distinct responses to certain targeted therapies. Herein, current DMARDs and biologic agents as well as the potential role of emerging therapeutics will be reviewed. PMID- 25125589 TI - Impact of musculoskeletal pain on insomnia onset: a prospective cohort study. AB - OBJECTIVE: Pain, the most common manifestation of rheumatological conditions, is highly prevalent among older adults, with worse health outcomes found in those with co-morbid insomnia. Proactive prevention of insomnia may reduce the overall disease burden of pain and rheumatological conditions. To inform such development, this study examined the role of pain, physical limitation and reduced social participation in predicting and mediating insomnia onset. METHODS: A prospective cohort study was conducted involving 6676 individuals >=50 years of age who completed questionnaires at baseline and a 3-year follow-up. Participants were classified into none, some and widespread pain according to the ACR criteria. Logistic regression was used to examine the relationship between baseline pain and insomnia onset at 3 years. Path analysis was used to test for the mediating role of physical limitation and social participation restriction. RESULTS: Some [adjusted odds ratio (AOR) 1.57 (95% CI 1.15, 2.13)] and widespread [2.13 (1.66, 3.20)] pain increased the risk of insomnia onset at 3 years, after adjusting for age, gender, socio-economic class, education, anxiety, depression, sleep and co-morbidity at baseline. The combination of physical limitation and reduced social participation explained up to 68% of the effect of some pain on insomnia onset and 66% of the effect of widespread pain on insomnia onset. CONCLUSION: There was a dose-response association between the extent of pain at baseline and insomnia onset at 3 years that was substantially mediated by physical limitation and reduced social participation. Targeting physical limitation and social participation in older people with pain may buffer co morbid insomnia, reducing the overall disease burden. PMID- 25125590 TI - Comparison between three systems of classification criteria in juvenile systemic lupus erythematous. AB - OBJECTIVE: The most widely used classification criteria for SLE are those derived and validated in adult patients by the ACR. Alternatives include the Boston weighted (BW) and SLICC criteria. The aim of this study was to compare the performance of BW and SLICC criteria with the 1997 ACR criteria in a JSLE cohort. METHODS: Cases were JSLE patients and controls were patients with other rheumatic diseases attending a tertiary centre in the past 10 years. Data were retrospectively collected to establish the ACR, BW and SLICC criteria fulfilled at the first visit and within the first year of follow-up. A consensus diagnosis of JSLE established by the same group of highly experienced paediatric rheumatologists was chosen as the standard of reference. RESULTS: One hundred and seventy-three patients were included: 81 JSLE and 92 controls. There was a sharp increase in sensitivity and prevalence of all criteria within the first year of follow-up. The BW criteria had higher sensitivity than the ACR criteria (81.5% vs 58%, P < 0.001) at the first visit, but lower specificity in both periods. SLICC criteria had higher sensitivity (82.7% vs 58%, P < 0.001) at the first visit, but similar specificity in both periods. CONCLUSION: In this JSLE population, the SLICC criteria performed best in terms of sensitivity and accuracy at the first visit and within the first year of follow-up. PMID- 25125591 TI - Factors influencing work disability in psoriatic arthritis: first results from a large UK multicentre study. AB - OBJECTIVE: The aim of this study was to determine the extent to which structural damage, clinical disease activity, demographic and social factors are associated with work disability (WD) in PsA. METHODS: Four hundred patients fulfilling CASPAR (Classification Criteria for Psoriatic Arthritis) criteria for PsA were recruited from 23 hospitals across the UK. Demographic, socio-economic, work, clinical and radiographic data were collected. WD was assessed with the Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP) questionnaire reporting WD as a percentage of absenteeism (work time missed), presenteeism (impairment at work/reduced effectiveness) and work productivity loss (overall work impairment/absenteeism plus presenteeism). Logistic and linear regressions were conducted to investigate associations with WD. RESULTS: Two hundred and thirty-six participants of any age were in work. Absenteeism, presenteeism and productivity loss rates were 14% (s.d. 29.0), 39% (s.d. 27.2) and 46% (s.d. 30.4), respectively. Ninety-two (26%) participants of working age were unemployed. Greater age, disease duration of 2-5 years and worse physical function were associated with unemployment. Patients reported that employer awareness and helpfulness exerted a strongly positive influence on remaining in employment. Higher levels of global and joint-specific disease activity and worse physical function were associated with greater levels of presenteeism and productivity loss among those who remained in work. CONCLUSION: Reduced effectiveness at work was associated with measures of disease activity, whereas unemployment, considered the endpoint of WD, was associated with employer factors, age and disease duration. A longitudinal study is under way to determine whether treatment to reduce disease activity ameliorates WD in the real-world setting. PMID- 25125592 TI - Interferon gene expression signature in rheumatoid arthritis neutrophils correlates with a good response to TNFi therapy. AB - OBJECTIVE: The aim of this study was to use whole transcriptome sequencing (RNA Seq) of RA neutrophils to identify pre-therapy gene expression signatures that correlate with disease activity or response to TNF inhibitor (TNFi) therapy. METHODS: Neutrophils were isolated from the venous blood of RA patients (n = 20) pre-TNFi therapy and from healthy controls (n = 6). RNA was poly(A) selected and sequenced on the Illumina HiSeq 2000 platform. Reads were mapped to the human genome (hg19) using TopHat and differential expression analysis was carried out using edgeR (5% false discovery rate). Signalling pathway analysis was carried out using Ingenuity Pathway Analysis (IPA) software. IFN signalling was confirmed by western blotting for phosphorylated signal transducer and activator of transcription (STAT) proteins. Response to TNFi was measured at 12 weeks using change in the 28-item DAS (DAS28). RESULTS: Pathway analysis with IPA predicted activation of IFN signalling in RA neutrophils, identifying 178 IFN-response genes regulated by IFN-alpha, IFN-beta or IFN-gamma (P < 0.01). IPA also predicted activation of STAT1, STAT2 and STAT3 transcription factors in RA neutrophils (P < 0.01), which was confirmed by western blotting. Expression of IFN-response genes was heterogeneous and patients could be categorized as IFN high or IFN-low. Patients in the IFN-high group achieved a better response to TNFi therapy [DeltaDAS28, P = 0.05, odds ratio (OR) 1.4 (95% CI 1.005, 1.950)] than patients in the IFN-low group. The level of expression of IFN-response genes (IFN score) predicted a good response [European League Against Rheumatism (EULAR) criteria] to TNFi using receiver operating characteristic curve analysis (area under the curve 0.76). CONCLUSION: IFN-response genes are significantly up regulated in RA neutrophils compared with healthy controls. Higher IFN-response gene expression in RA neutrophils correlates with a good response to TNFi therapy. PMID- 25125593 TI - Tumour necrosis factor inhibitor therapy and infection risk in axial spondyloarthritis: results from a longitudinal observational cohort. AB - OBJECTIVES: Long-term data on infection risk in axial SpA (axSpA) are sparse. TNF inhibitors (TNFis) are increasingly being used in axSpA, with infection being the most important adverse event. We aimed to investigate the frequency of infections in axSpA and to identify factors predisposing to infection. METHODS: Data were extracted from a longitudinal observational cohort of patients with axSpA. Infection rates were calculated and multivariate analysis was performed to investigate the association of independent variables with infection. RESULTS: Data were analysed for 440 patients followed for a total of 1712 patient-years (pys). A total of 259 infections, of which 23 were serious, were recorded in 185 patients. The overall rate of any infection was 15 (95% CI 13, 17)/100 pys and the serious infection rate was 1.3 (95% CI 0.9, 2.0)/100 pys. There was no significant difference in the rate of any infection or serious infection in patients on TNFis compared with patients never on biologic agents. In the multivariate analysis, DMARD treatment, but not TNFi treatment, was associated with risk of infection. Age, disease duration, smoking status, BASFI, BASDAI, co morbidity score and hospitalization were not associated with an increased risk of infection. CONCLUSION: The serious infection rate in axSpA in this observational cohort is low when compared with rates reported in other rheumatic diseases. Biologic use was not a significant risk factor for serious infection. PMID- 25125596 TI - In situ exposure assessment of intermediate frequency fields of diverse devices. AB - In this study, in situ exposure assessment of both electric and magnetic fields of different intermediate frequency (IF) sources is investigated. The authors investigated smart boards and touchscreens, energy-saving bulbs, fluorescent lamps, a portable hearing unit and an electrosurgical unit (ESU). For most of these sources, the electric field is the dominating quantity. International Commission on Non-Ionizing Radiation Protection reference levels are exceeded for touchscreens (44 kHz: up to 155.7 V m(-1) at 5 cm), energy-saving bulbs (38-52 kHz: up to 117.3 V m(-1)), fluorescent lamps (52 kHz: up to 471 V m(-1) at 5 cm) and ESUs (up to 920 kHz: 792 V m(-1) at 0.5 cm). Magnetic field strengths up to 1.8 and 10.5 A m(-1) were measured close to the ESU and portable hearing unit (69 V m(-1)), respectively. Large differences of measured field values exist among the various operating modes of the IF equipment. Compliance distances for general public range from 15.3 cm (touchscreen) to 25 cm (fluorescent lamps). PMID- 25125594 TI - Twenty-two points to consider for clinical trials in systemic sclerosis, based on EULAR standards. AB - OBJECTIVE: SSc is clinically and aetiopathogenically heterogeneous. Consensus standards for more uniform trial design and selection of outcome measures are needed. The objective of this study was to develop evidence-based points to consider (PTCs) for future clinical trials in SSc. METHODS: Thirteen international SSc experts experienced in SSc clinical trial design were invited to participate. One researcher with experience in systematic literature review and three trainees were also included. A systematic review using PubMed and the Cochrane Central Register of Controlled Trials was conducted and PTCs when designing clinical trials in SSc were developed. As part of that development we conducted an Internet-based Delphi exercise regarding the main points to be made in the consensus statement. Consensus was defined as achieving a median score of >=7 of 9. RESULTS: By consensus, the experts decided to develop PTCs for each individual organ system. The current document provides a unifying outline on PTCs regarding general trial design, inclusion/exclusion criteria and analysis. Consensus was achieved regarding all the main points of the PTCs. CONCLUSION: Using European League Against Rheumatism suggestions for PTCs, a general outline for PTCs for controlled clinical trials in SSc was developed. Specific outlines for individual organ systems are to be published separately. This general outline should lead to more uniform and higher-quality trials and clearly delineate areas where further research is needed. PMID- 25125597 TI - Effects of pupil center shift on ocular aberrations. AB - PURPOSE: We investigated effects of pupil shifts, occurring with changes in luminance and accommodation stimuli, on refraction components and higher-order aberrations. METHODS: Participants were young and older groups (n = 20; 22 +/- 2 years; age range, 18-25 years; and n = 19, 49 +/- 4 years, 45-58 years, respectively). Aberrations/refractions at 4- and 3-mm diameters were compared between centered and decentered pupils for low (background, 0.01 cd/m(2), 0 diopters [D]), and high (6100 cd/m(2), 4 or 6 D) stimuli. Decentration was the difference between pupil centers for low and high stimuli. Clinical important changes with decentration were: M at +/- 0.50 or +/- 0.25 D, J180 and J45 at +/- 0.25 or +/- 0.125 D, HORMS at +/- 0.05 MUm, C(3, 1) at +/- 0.05 MUm, and C(4, 0) at +/- 0.05 MUm. RESULTS: Because of small pupil shifts in most participants (mean 0.26 mm), there were few important changes in most refraction components and higher-order aberration terms. However, M changed by >0.25 D for a third of participants with 4-mm pupils. When determining refractions from second to sixth order aberration coefficients, the more stringent criteria gave 76/534 (14%) possible important changes. Some participants had large pupil shifts with considerable aberration changes. Comparisons at the high stimulus were possible for only 11 participants because of small pupils. When refractions were determined from second order aberration coefficients only, only 35 (7%) had important changes for the more stringent criteria. CONCLUSIONS: Usually pupil shifts with changes in stimulus conditions have little influence on aberrations, but they can with high shifts. The number of aberrations orders that are considered as contributing to refraction influences the proportion of cases that might be considered clinically important. PMID- 25125595 TI - A cluster of methylations in the domain IV of 25S rRNA is required for ribosome stability. AB - In all three domains of life ribosomal RNAs are extensively modified at functionally important sites of the ribosome. These modifications are believed to fine-tune the ribosome structure for optimal translation. However, the precise mechanistic effect of modifications on ribosome function remains largely unknown. Here we show that a cluster of methylated nucleotides in domain IV of 25S rRNA is critical for integrity of the large ribosomal subunit. We identified the elusive cytosine-5 methyltransferase for C2278 in yeast as Rcm1 and found that a combined loss of cytosine-5 methylation at C2278 and ribose methylation at G2288 caused dramatic ribosome instability, resulting in loss of 60S ribosomal subunits. Structural and biochemical analyses revealed that this instability was caused by changes in the structure of 25S rRNA and a consequent loss of multiple ribosomal proteins from the large ribosomal subunit. Our data demonstrate that individual RNA modifications can strongly affect structure of large ribonucleoprotein complexes. PMID- 25125598 TI - The combined effect of azithromycin and insulin-like growth factor-1 on cultured human meibomian gland epithelial cells. AB - PURPOSE: Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease, a prevalent disorder severely affecting patients' quality of life but has no cure. We have discovered that azithromycin, a topical antibiotic used off label to treat MGD-associated posterior blepharitis, directly acts on the human meibomian gland epithelial cells (HMGECs) to promote their differentiation, and in doing so, reduces cell proliferation. We have also found that insulin-like growth factor-1 (IGF-1), a drug approved by the Food and Drug Administration primarily used to treat dwarfism, stimulates the proliferation and lipid accumulation in these cells. We hypothesize that the combination of azithromycin and IGF-1 will promote cellular differentiation and lipid accumulation, while preserving the normal proliferation of HMGECs. METHODS: We cultured immortalized HMGECs with vehicle, 10 nM IGF-1, 10 MUg/mL azithromycin, or a combination of IGF 1 and azithromycin for 5 to 13 days. Cells were evaluated for intracellular neutral lipids and lysosome accumulation by different staining methods; lipid composition of cell lysates were analyzed using high-performance thin-layer chromatography; proteins of interest (sterol regulatory element binding protein-1 [SREBP-1], cyclins B1 and D1) were measured by immunoblotting, and cell numbers were counted using a hemocytometer. RESULTS: Our findings demonstrate that the combination of azithromycin and IGF-1 promotes the differentiation and lipid accumulation of HMGECs, while preserving their normal proliferation rate. This combined treatment also increased the levels of neutral lipids, phospholipids, and SREBP-1, and restored cyclin B1 content to control amounts. CONCLUSIONS: Our results support our hypothesis, and this combination regime may represent a unique and effective treatment of MGD. PMID- 25125599 TI - Long-term therapeutic effects of mesenchymal stem cells compared to dexamethasone on recurrent experimental autoimmune uveitis of rats. AB - PURPOSE: We tested the long-term effects of different regimens of mesenchymal stem cell (MSC) administration in a recurrent experimental autoimmune uveitis (rEAU) model in rats, and compared the efficacy of MSC to that of dexamethasone (DEX). METHODS: One or two courses of MSC treatments were applied to R16-specific T cell-induced rEAU rats before or after disease onsets. The DEX injections were given for 7 or 50 days continuously after disease onsets. Clinical appearances were observed until the 50th day after transfer. On the 10th day, T cells from control and MSC groups were analyzed by flow cytometry. Supernatants from the proliferation assay and aqueous humor were collected for cytokine detection. Functions of T cells and APCs in spleens also were studied by lymphocyte proliferation assays. RESULTS: One course of MSC therapy, administered after disease onset, led to a lasting therapeutic effect, with a decreased incidence, reduced mean clinical score, and reduced retinal impairment after 50 days of observation, while multiple courses of treatment did not improve the therapeutic benefit. Although DEX and MSCs equally reduced the severity of the first episode of rEAU, the effect of DEX was shorter lasting, and DEX therapy failed to control the disease even with long periods of treatment. The MSCs significantly decreased T helper 1 (Th1) and Th17 responses, suppressed the function of antigen presenting cells, and upregulated T regulatory cells. CONCLUSIONS: These results suggested that MSCs might be new corticosteroid spring agents, while providing fewer side effects and longer lasting suppressive effects for recurrent uveitis. PMID- 25125600 TI - Transgenic mice expressing mutated Tyr437His human myocilin develop progressive loss of retinal ganglion cell electrical responsiveness and axonopathy with normal iop. AB - PURPOSE: To characterize age-related changes of retinal ganglion cell (RGC) function, IOP, and anatomical markers of axon/glia integrity in a transgenic mouse expressing Tyr437His mutant of human myocilin protein. METHODS: Retinal ganglion cell electrical responsiveness was tested with pattern electroretinogram (PERG) in 11 transgenic mice expressing mutated myocilin at different ages over 18 months under ketamine/xylazine anesthesia. Twelve age-matched C57BL/6J mice also were tested as controls. Intraocular pressure was measured with a Tonolab tonometer. Immunohistochemistry for GFAP and neurofilament was performed on dissected optic nerve heads. RESULTS: In transgenic mice expressing mutated myocilin, the PERG amplitude progressively decreased with increasing age by approximately 50%, whereas the PERG peak latency increased by approximately 40 ms (ANOVA, P < 0.05). In contrast, PERGs of young and old control mice had similar amplitudes and peak latencies. In transgenic mice, GFAP staining was more intense and extended than in control mice, and increased with increasing age; neurofilament staining showed swollen and partially degenerated axons in old transgenic mice. The IOP of young transgenic mice was similar to that of control mice and did not significantly change with increasing age. CONCLUSIONS: Transgenic mice expressing mutated human myocilin display progressive age-related changes in RGC electrical responsiveness that are not associated with IOP elevation but are associated with marked astrogliosis and axonopathy. Our results support the view that MYOC expression in the optic nerve may impact structural, metabolic, or neurotrophic support to RGC axons, thereby influencing their susceptibility to glaucomatous damage independently of IOP. PMID- 25125601 TI - Pseudomonas aeruginosa infectious keratitis in a high oxygen transmissible rigid contact lens rabbit model. AB - PURPOSE: To establish a rabbit model of infectious Pseudomonas aeruginosa keratitis using ultrahigh oxygen transmissible rigid lenses and characterize the frequency and severity of infection when compared to a non-oxygen transmissible lens material. METHODS: Rabbits were fit with rigid lenses composed of ultrahigh and non-oxygen transmissible materials. Prior to wear, lenses were inoculated with an invasive corneal isolate of P. aeruginosa stably conjugated to green fluorescent protein (GFP). Corneas were examined before and after lens wear using a modified Heidelberg Rostock Tomograph in vivo confocal microscope. Viable bacteria adherent to unworn and worn lenses were assessed by standard plate counts. The presence of P. aeruginosa-GFP and myeloperoxidase-labeled neutrophils in infected corneal tissue was evaluated using laser scanning confocal microscopy. RESULTS: The frequency and severity of infectious keratitis was significantly greater with inoculated ultrahigh oxygen transmissible lenses. Infection severity was associated with increasing neutrophil infiltration and in severe cases, corneal melting. In vivo confocal microscopic analysis of control corneas following lens wear confirmed that hypoxic lens wear was associated with mechanical surface damage, whereas no ocular surface damage was evident in the high-oxygen lens group. CONCLUSIONS: These data indicate that in the absence of adequate tear clearance, the presence of P. aeruginosa trapped under the lens overrides the protective effects of oxygen on surface epithelial cells. These findings also suggest that alternative pathophysiological mechanisms exist whereby changes under the lens in the absence of frank hypoxic damage result in P. aeruginosa infection in the otherwise healthy corneal epithelium. PMID- 25125602 TI - Constitutive and LPS-induced expression of MCP-1 and IL-8 by human uveal melanocytes in vitro and relevant signal pathways. AB - PURPOSE: Melanocytes are one of the major cellular components in the uvea. Interleukin-8/CXCL8 and monocyte chemoattractant protein-1 (MCP-1/CCL2) are the two most important proinflammatory chemokines. We studied the constitutive and lipopolysaccharide (LPS)-induced expression of IL-8 and MCP-1 in cultured human uveal melanocytes (UM) and explored the relevant signal pathways. METHODS: Conditioned media and cells were collected from UM cultured in medium with and without stimulation of LPS. Interleukin-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Nuclear factor (NF)-kappaB in nuclear extracts and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases1/2 (ERK1/2), and c-Jun N-terminal kinase1/2 (JNK1/2) in cells cultured with and without LPS were measured by ELISA kits. Inhibitors of p38 (SB203580), ERK1/2 (UO1026), JNK1/2 (SP600125), and NF kappaB (BAY11-7082) were added to the cultures to evaluate their effects. RESULTS: Low levels of IL-8 and MCP-1 proteins were detected in the conditioned media in UM cultured without serum. Lipopolysaccharide (0.01-1 MUg/mL) increased IL-8 and MCP-1 mRNAs and proteins levels in a dose- and time-dependent manner, accompanied by a significant increase of phosphorylated JNK1/2 in cell lysates and NF-kappaB in nuclear extracts. Nuclear factor-kappaB and JNK1/2 inhibitors significantly blocked LPS-induced expression of IL-8 and MCP-1. CONCLUSIONS: This is the first report on the expression and secretion of chemokines by UM. The data suggest that UM may play a role in the pathogenesis of ocular inflammatory diseases. PMID- 25125604 TI - The staining pattern of brilliant blue G during macular hole surgery: a clinicopathologic study. AB - PURPOSE: To describe the intraoperative staining pattern of the internal limiting membrane (ILM)-specific dye Brilliant Blue G (BBG) in a cohort of patients with idiopathic macular holes; to analyze the associations of the staining pattern with pre- and postoperative variables and to correlate the staining pattern with transmission electron microscopy (TEM) of the excised ILM. METHODS: Fifty-five consecutive patients were studied. The staining pattern was divided into three subtypes based on the intraoperative appearance. The presence of a narrow rim of nonstaining around the macular hole (MH) edge was noted and measured. In the final 21 patients, the excised ILM was examined with TEM. RESULTS: The pattern of staining observed was categorized as uniform in 33 patients (60%), patchy nonstaining in 17 (31%), and no visible staining in 5 (9%). The staining pattern correlated with the MH stage. In the patients with uniform or patchy staining, a nonstaining rim was observed in 26 (52%) of the 50. The presence of a rim was associated with a greater hole diameter and lower postoperative visual acuity. The stain pattern correlated significantly with the amount of cellular tissue on the vitreous side of the ILM on TEM, with a greater proportion of multicellular layer membranes and new collagen in the incomplete staining groups. CONCLUSIONS: A variety of nonstaining patterns around macular holes can be observed using BBG, and these patterns correlate to the amount of cellular tissue on the vitreous side of the ILM seen histologically. These patterns could be used to guide the ILM peeling requirement or extent in future studies. PMID- 25125603 TI - Sunlight exposure, pigmentation, and incident age-related macular degeneration. AB - PURPOSE: Examine potential effects of sunlight exposure, hair color, eye color, and selected gene single-nucleotide polymorphisms (SNPs) on incidence of AMD. METHODS: Subjects participated in up to five examinations over a 20-year period. Eye color, self-reported hair color as a teenager, and sunlight exposure were ascertained at the baseline examination. Presence and severity of AMD and its lesions were determined via fundus photographs. Genetic data were available on a subset of participants. The SNPs CFH Y402H rs1061170 and ARMS2 A69S rs10490924 were used to analyze genetic risk of AMD; OCA2 rs4778241 and HERC2 rs12913832 represented genetic determinants of eye color. RESULTS: Incidence of early AMD was higher in blond/red-haired persons compared with brown/black-haired persons (hazard ratio [HR] 1.25, P = 0.02) and in persons with high sun exposure in their thirties (HR 1.41, P = 0.02). However, neither was significant after adjustment for multiple comparisons. Eye (HR 1.36, P = 0.006) and hair color (HR 1.42, P = 0.003) were associated with incidence of any retinal pigmentary abnormalities (RPAs). Both remained significant after adjustment for multiple comparisons. Neither presence of alleles for light-colored eyes nor those associated with high risk of late AMD altered the association of eye or hair color with early AMD. None of the characteristics studied were significantly associated with late AMD. CONCLUSIONS: Modest associations of eye color, hair color, and HERC2 genotype with any RPAs were found. Genes for AMD did not affect these associations. Eye color phenotype was more strongly associated with outcomes than HERC2 or OCA2 genotype. PMID- 25125605 TI - Comparative transcriptomic analysis of cultivated limbal epithelium and donor corneal tissue reveals altered wound healing gene expression. AB - PURPOSE: The improved surgical outcomes associated with transplantation of cultivated amniotic membrane expanded limbal epithelium (AMLE) compared to traditional donor methods has led to substantial adoption of this technique for treatment of limbal stem cell deficiency. METHODS: The mRNA expression profiles of AMLE and CE were assayed using microarrays. Transcripts with a 1.5-fold change in either direction in addition to a Bonferroni adjusted P value < 0.05 were considered to be differentially expressed. Expression changes detected by microarray profiling and important corneal-limbal markers were assessed using quantitative real-time PCR (qRT-PCR) and immunofluorescence staining. RESULTS: A total of 487 probe sets (319 upregulated and 168 downregulated) were found to be differentially expressed between AMLE and CE. Enrichment analysis revealed significant overrepresentation of multiple biological processes (e.g., response to wounding, wound healing, and regulation of cell morphogenesis) within the differentially expressed gene list. The expression of a number of genes that were upregulated (ABCG2, S100A9, ITGA5, TIMP2, FGF5, PDGFC, SEMA3A) and downregulated (KLF4, P63alpha) in AMLE was confirmed using qRT-PCR. Immunofluorescence confirmed that AMLE cultures were P63alpha, ABCG2, CK3, CK12, and E-cadherin (E cad) positive. CONCLUSIONS: In this study, we have shown that genes associated with wound healing processes are upregulated in AMLE. These gene expression changes may contribute to corneal restoration and the positive outcomes associated with transplantation. PMID- 25125606 TI - Wnt and extraocular muscle sparing in amyotrophic lateral sclerosis. AB - PURPOSE: The extraocular muscles (EOM) and their motor neurons are spared in amyotrophic lateral sclerosis (ALS). In limb muscle, axon retraction from the neuromuscular junctions occurs early in the disease. Wnts, a conserved family of secreted signaling molecules, play a critical role in neuromuscular junction formation. This is the first study to examine Wnt signaling for its potential involvement in maintenance of normal morphology in EOM in ALS. METHODS: Extraocular muscle and limb muscle axons, neuromuscular junctions, and myofibers from control, aging, and ALS subjects and the SOD1(G93A) mouse model of ALS were quantified for their expression of Wnt1, Wnt3a, Wnt5a, Wnt7a, and beta-catenin. RESULTS: All four Wnt isoforms were expressed in most axon profiles in all human EOM. Significantly fewer were positive for Wnt1, Wnt3a, and Wnt7a in the human limb muscles. Similar differential patterns in Wnt myofiber expression were also seen except in the case of Wnt7a, where expression was elevated. In the SOD1(G93A) mouse, all four Wnt isoforms were significantly decreased in the neuromuscular junctions at the terminal stage compared to values in age-matched controls. beta-Catenin was activated in a subset of myofibers in EOM and limb muscle in all subjects. CONCLUSIONS: The differences in expression of Wnts in EOM and limb muscle, particularly at the neuromuscular junction level, suggest that they play a role in the pathophysiology of ALS. Collectively, the data support a role for signaling of Wnts in the preservation of the EOM in ALS and their dysregulation and the subsequent development of pathology in the ALS limb muscles. PMID- 25125608 TI - Association between blood cadmium level and age-related macular degeneration in a representative Korean population. AB - PURPOSE: To investigate the association between blood cadmium level and AMD. METHODS: This population-based, cross-sectional study using a nationwide, systemically stratified, multistage, clustered sampling method included 4933 subjects older than 40 years who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) between 2008 and 2012 and had fundus photographs taken. All participants underwent a standardized interview, evaluation of blood cadmium concentrations, and comprehensive ophthalmic examination. A 45 degrees digital fundus photograph was taken from both eyes under physiologic mydriasis, and were graded using the international classification and grading system for AMD. RESULTS: Mean blood cadmium levels were 1.47 MUg/L in women and 1.19 MUg/L in men. After adjusting for potential confounders, including age, sex, and smoking status, the odds ratio (OR) for AMD was significantly increased in the highest quintile blood cadmium group (OR, 1.96; 95% confidence interval [CI], 1.17-3.29; P for trend = 0.017). This association between blood cadmium level and AMD was significant in men (OR, 2.11; 95% CI, 1.11-4.02; P for trend = 0.024), but not in women (OR, 1.29; 95% CI, 0.70 2.52; P for trend = 0.158). CONCLUSIONS: This study provides the first epidemiologic evidence that higher blood cadmium level is associated with AMD. Results of the present study indicate that an elevated cadmium burden may increase the risk of AMD development. PMID- 25125607 TI - Loss of Raf-1 kinase inhibitory protein delays early-onset severe retinal ciliopathy in Cep290rd16 mouse. AB - PURPOSE: Mutations in the cilia-centrosomal protein of centrosomal protein of 290 kDa (CEP290) result in severe ciliopathies, including autosomal recessive early onset childhood blindness disorder Leber congenital amaurosis (LCA). The Cep290(rd16) (retinal degeneration 16) mouse model of CEP290-LCA exhibits accumulation of CEP290-interacting protein Raf-1 kinase inhibitory protein (RKIP) prior to onset of retinal degeneration (by postnatal day P14). We hypothesized that reducing RKIP levels in the Cep290(rd16) mouse will delay or improve retinal phenotype. METHODS: We generated double mutant mice by combining the Cep290(rd16) and Rkip(ko) alleles (Cep290(rd16):Rkip(+/ko) and Cep290(rd16):Rkip(ko/ko)). Retinal function was assessed by ERG and retinal morphology and protein trafficking were assessed by histology, transmission electron microscopy (TEM), and immunofluorescence analysis. Cell death was examined by apoptosis. RESULTS: Prior to testing our hypothesis, we examined ERG and retinal morphology of Rkip(ko/ko) mice and did not find any detectable differences compared with wild type mice. The Cep290(rd16):Rkip(+/ko) mice exhibited similar retinopathy as Cep290(rd16); however, Cep290(rd16): Rkip(ko/ko) double knockout mice demonstrated a substantial improvement (>9-fold) in photoreceptor function and structure at P18 as of Cep290(rd16) mice. We consistently detected transient preservation of photoreceptors at P18 and polarized trafficking of opsins to sensory cilia in the double mutant mice; however, retinal degeneration ensued by P30. CONCLUSIONS: Our studies implicate CEP290-RKIP pathway in CEP290-retinal degeneration and suggest that targeting RKIP levels can delay photoreceptor degeneration, assisting in extending the time-window for treating such rapidly progressing blindness disorder. PMID- 25125609 TI - A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease. AB - Mutations in VCP have been reported to account for a spectrum of phenotypes that include inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia, hereditary spastic paraplegia, and 1-2% of familial amyotrophic lateral sclerosis. We identified a novel VCP mutation (p.Glu185Lys) segregating in an autosomal dominant Charcot-Marie-Tooth disease type 2 family. Functional studies showed that the Glu185Lys variant impaired autophagic function leading to the accumulation of immature autophagosomes. VCP mutations should thus be considered for genetically undefined Charcot-Marie-Tooth disease type 2. PMID- 25125610 TI - Neuroanatomical precursors of dyslexia identified from pre-reading through to age 11. AB - Developmental dyslexia is a common reading disorder that negatively impacts an individual's ability to achieve literacy. Although the brain network involved in reading and its dysfunction in dyslexia has been well studied, it is unknown whether dyslexia is caused by structural abnormalities in the reading network itself or in the lower-level networks that provide input to the reading network. In this study, we acquired structural magnetic resonance imaging scans longitudinally from 27 Norwegian children from before formal literacy training began until after dyslexia was diagnosed. Thus, we were able to determine that the primary neuroanatomical abnormalities that precede dyslexia are not in the reading network itself, but rather in lower-level areas responsible for auditory and visual processing and core executive functions. Abnormalities in the reading network itself were only observed at age 11, after children had learned how to read. The findings suggest that abnormalities in the reading network are the consequence of having different reading experiences, rather than dyslexia per se, whereas the neuroanatomical precursors are predominantly in primary sensory cortices. PMID- 25125611 TI - ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism. AB - Two siblings with fatal Leigh disease had increased excretion of S-(2 carboxypropyl)cysteine and several other metabolites that are features of 3 hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, a rare defect in the valine catabolic pathway associated with Leigh-like disease. However, this diagnosis was excluded by HIBCH sequencing and normal enzyme activity. In contrast to HIBCH deficiency, the excretion of 3-hydroxyisobutyryl-carnitine was normal in the children, suggesting deficiency of short-chain enoyl-CoA hydratase (ECHS1 gene). This mitochondrial enzyme is active in several metabolic pathways involving fatty acids and amino acids, including valine, and is immediately upstream of HIBCH in the valine pathway. Both children were compound heterozygous for a c.473C > A (p.A158D) missense mutation and a c.414+3G>C splicing mutation in ECHS1. ECHS1 activity was markedly decreased in cultured fibroblasts from both siblings, ECHS1 protein was undetectable by immunoblot analysis and transfection of patient cells with wild-type ECHS1 rescued ECHS1 activity. The highly reactive metabolites methacrylyl-CoA and acryloyl-CoA accumulate in deficiencies of both ECHS1 and HIBCH and are probably responsible for the brain pathology in both disorders. Deficiency of ECHS1 or HIBCH should be considered in children with Leigh disease. Urine metabolite testing can detect and distinguish between these two disorders. PMID- 25125612 TI - Does dominant pedunculopontine nucleus exist? PMID- 25125613 TI - Reply: Does dominant pedunculopontine nucleus exist? PMID- 25125615 TI - Learning to be a consultant: what should be taught. PMID- 25125616 TI - An analysis of clinical consultation activities in clinical pathology: who requests help and why. AB - OBJECTIVES: To examine the distribution of callers who made consultation requests and to identify associations between caller categories and consultation topics. METHODS: Review of prospectively collected database of consultations. RESULTS: Direct care personnel made more consultation requests than non-direct care personnel. Consultation topics varied by caller type. Direct care personnel requested more consultations on test interpretation and few consultations on test selection than laboratory personnel. Differences in consultation requests by primary care physicians and specialists were significant. CONCLUSIONS: At our laboratory, consultation requests primarily originate from primary care physicians. Consultation requests vary by caller type. PMID- 25125614 TI - Diffusion tensor imaging and neurocognition in survivors of childhood acute lymphoblastic leukaemia. AB - Survivors of childhood acute lymphoblastic leukaemia are at risk for neurocognitive impairment, though little information is available on its association with brain integrity, particularly for survivors treated without cranial radiation therapy. This study compares neurocognitive function and brain morphology in long-term adult survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean (standard deviation) age at evaluation was 24.9 (3.6) years for the chemotherapy group and 26.7 (3.4) years for the cranial radiation therapy group, while time since diagnosis was 15.0 (1.7) and 23.9 (3.1) years, respectively. Brain grey and white matter volume and diffusion tensor imaging was compared between survivor groups and to 23 healthy controls with a mean (standard deviation) age of 23.1 (2.6) years. Survivors treated with chemotherapy alone had higher fractional anisotropy in fibre tracts within the left (P < 0.05), but not in the right, hemisphere when compared to controls. Survivors of acute lymphoblastic leukaemia, regardless of treatment, had a lower ratio of white matter to intracranial volume in frontal and temporal lobes (P < 0.05) compared with control subjects. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone performed worse in processing speed (P < 0.001), verbal selective reminding (P = 0.01), and academics (P < 0.05) compared to population norms and performed better than survivors treated with cranial radiation therapy on verbal selective reminding (P = 0.02), processing speed (P = 0.05) and memory span (P = 0.009). There were significant associations between neurocognitive performance and brain imaging, particularly for frontal and temporal white and grey matter volume. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone demonstrated significant long-term differences in neurocognitive function and altered neuroanatomical integrity. These results suggest substantial region specific white matter alterations in survivors of acute lymphoblastic leukaemia possibly resulting in restricted radial diffusion due to the compaction of neuronal fibres. PMID- 25125617 TI - Loss of blast heterogeneity in myelodysplastic syndrome and other chronic myeloid neoplasms. AB - OBJECTIVES: Flow cytometry immunophenotyping has been suggested as an adjunctive technique in the evaluation of myeloid malignancies, especially in the myelodysplastic syndromes. However, its use has been limited due to complexity and cost restraints. The goal of this study is to attempt a simpler approach to flow cytometry immunophenotyping in myeloid neoplasms. METHODS: We analyzed bone marrow specimens of 45 selected patients and an additional 99 consecutive random patients using a limited antibody panel. RESULTS: Normal CD34-positive blasts show a characteristic pattern of CD13/HLA-DR expression, with three readily identifiable subpopulations. In contrast, myeloid neoplasms frequently show loss of this heterogeneity. CONCLUSIONS: Analysis of a limited antibody panel with a focus on CD13/HLA-DR expression provides relatively high specificity and sensitivity for the detection of myeloid neoplasms. PMID- 25125619 TI - Rapid detection of the active cardiac glycoside convallatoxin of lily of the valley using LOCI digoxin assay. AB - OBJECTIVES: To explore the luminescent oxygen channeling technology-based digoxin immunoassay (LOCI digoxin assay) for rapid detection of lily of the valley extract and convallatoxin. The potential in vitro binding of convallatoxin with Digibind was also evaluated. METHODS: Aliquots of a drug-free serum pool and a digoxin serum pool were supplemented with lily of the valley extract or convallatoxin, and then apparent digoxin concentrations were measured using the LOCI digoxin assay. Mice were administered lily of the valley extract or 50 MUg of convallatoxin, and digoxin concentrations in serum specimens were measured 1 and 2 hours after gavage. Aliquots of a serum pool supplemented with convallatoxin or lily of the valley extract were further supplemented with various concentrations of Digibind and free apparent digoxin concentrations were measured. RESULTS: Apparent digoxin concentrations were observed when aliquots of a drug-free serum pool were supplemented with convallatoxin or lily of the valley extract, and also with convallatoxin or herbal extract. Bidirectional interference of convallatoxin and lily of the valley extract with serum digoxin measurement using the LOCI assay was also observed. Digibind was capable of binding convallatoxin in vitro. CONCLUSIONS: LOCI digoxin assay can be used for rapid detection of convallatoxin, and Digibind can bind convallatoxin in vitro. PMID- 25125618 TI - Comparison between invasive breast cancer with extensive peritumoral vascular invasion and inflammatory breast carcinoma: a clinicopathologic study of 161 cases. AB - OBJECTIVES: Extensive peritumoral neoplastic lymphovascular invasion (ePVI) is a marker of aggressiveness in invasive breast carcinoma (BC). METHODS: We explored the impact of ePVI on different BC subtypes. In a total of 2,116 BCs, 91 ePVI BCs, 70 inflammatory breast carcinomas (IBCs), and 114 casual BCs as a control group (CG-BC) were recruited. RESULTS: Patients affected by ePVI-BC were younger, had larger tumors, higher histologic grade, elevated Ki-67 score, Her2/neu overexpressed, and more lymph node metastases compared with CG-BC (P < .001). Interestingly, only younger mean age at diagnosis differentiated patients with ePVI-BC from patients affected by IBC. ePVI-BC showed a clinical outcome intermediate between the prognoses of IBC and CG-BC. CONCLUSIONS: Results suggest that ePVI-BC and IBC may share some pathologic processes, providing a novel perspective on the heterogeneity of BC. Epidemiologic data and molecular studies on gene expression features are needed to rationally classify these tumors into their identified subtypes. PMID- 25125620 TI - Mesothelin expression in pancreatic mucinous cysts. AB - OBJECTIVES: Mesothelin (MSLN) is a differentiation antigen found to be overexpressed in intraductal papillary mucinous neoplasms (IPMNs) and is a potential treatment target in pancreatic ductal adenocarcinoma. METHODS: From institutional archives, 114 cases of resected pancreatic mucinous cysts were identified, including IPMN and mucinous cystic neoplasm (MCN). Immunohistochemical analysis of MSLN was performed on representative sections. RESULTS: MSLN was seen more frequently in neoplastic epithelial cells from IPMN (39/52; P < .0005) and MCN (9/14; P < .0001) compared with unremarkable adjacent pancreatic and bile ducts (0/57) and benign foveolar and duodenal epithelium (0/21). When present, MSLN was diffusely expressed in neoplastic epithelium and only focally expressed in adjacent ducts (8/57). No significant difference was seen (P = .26) in MLSN expression between IPMN (79%) and MCN (83%) when only presence or absence was considered. CONCLUSION: Our findings suggest that MLSN can be used as a marker of neoplastic transformation of epithelial cells in pancreatic mucinous cysts. The findings can help identify neoplastic mucinous epithelium. PMID- 25125621 TI - Evaluation of napsin A, TTF-1, p63, p40, and CK5/6 immunohistochemical stains in pulmonary neuroendocrine tumors. AB - OBJECTIVE: A panel of immunohistochemical (IHC) stains frequently used to subclassify non-small cell lung cancers (NSCLCs) includes napsin A, TTF-1, CK5/6, p40, and p63. The expression profiles of these stains in neuroendocrine tumors have not been systematically evaluated. METHOD: Sixty-eight resected pulmonary neuroendocrine tumors, including 52 typical carcinoids (TCs), eight atypical carcinoids (ACs), seven small cell carcinomas (SCLCs) and one large cell neuroendocrine carcinoma (LCNEC), were stained for napsin A, TTF-1, p63, p40, and CK5/6. Tumors were scored as positive (>1% tumor cells reactive) or negative, and percentage of reactive tumor cells was recorded. RESULTS: Napsin A, p63, p40, and CK5/6 were consistently negative in neuroendocrine tumors. TTF-1 was positive in 17 of 52 TCs, 4 of 8 ACs, 5 of 7 SCLCs, and 0 of 1 LCNECs. CONCLUSION: Pulmonary neuroendocrine tumors have a distinct but nonspecific profile on IHC panel commonly applied to subclassify NSCLCs. They are napsin A-/p40-/p63-/CK5/6-/TTF 1+/-. Recognizing this profile may have value in separating neuroendocrine tumors from NSCLCs. PMID- 25125623 TI - Platelet mapping assay interference due to platelet activation in heparinized samples. AB - OBJECTIVES: Thromboelastography Platelet Mapping (TEGPM) is an assay designed to detect platelet inhibition due to aspirin or clopidogrel-like drugs. The purpose of this study was to evaluate potential causes of error in the design or operation of the assay. METHODS: We evaluated percent inhibition of platelets due to aspirin or clopidogrel using TEGPM, which measures clot viscoelastic maximum amplitude (MA) after activation with adenosine diphosphate (ADP) or arachidonic acid (AA) and subtraction of MA due to fibrin (MAFibrin). RESULTS: MAFibrin measured in heparinized blood showed an unstable increasing pattern in 28% of samples (16 of 58). The platelet aggregation inhibitor eptifibatide corrected increasing MAFibrin in 14 of 16 cases, while the thrombin inhibitor argatroban corrected increasing MAFibrin in six of 16 cases, suggesting that unanticipated platelet activation/ aggregation was a more important cause of unstable rising MAFibrin than uninhibited thrombin. The unstable increased MAFibrin falsely increased percent ADP inhibition on average from 19% to 38% and percent AA inhibition from 29% to 58%. Heparinized samples showed platelet clumping and had procoagulant platelet microvesicle levels double those in citrate anticoagulant. CONCLUSIONS: Unanticipated platelet activation/aggregation occurring in the heparinized TEGPM samples lead to erroneous percent inhibition results. PMID- 25125622 TI - A dual-fixed neutrophil substrate improves interpretation of antineutrophil cytoplasmic antibodies by indirect immunofluorescence. AB - OBJECTIVES: To determine whether the addition of a formalin-fixed neutrophil substrate could improve interpretation and prediction of autoantigenic specificity in antineutrophil cytoplasmic antibody (ANCA) testing. METHODS: Routine diagnostic samples sent for ANCA testing were analyzed prospectively on a dual substrate of both ethanol- and formalin-fixed neutrophils. Positive samples on ethanol-fixed neutrophils were deemed "typical" if formalin-fixed neutrophils also stained, and "atypical" if not. Indirect immunofluorescence (IIF) results were correlated with antimyeloperoxidase (MPO) and anti-proteinase 3 (PR3) results with an enzyme-linked immunosorbent assay (ELISA). RESULTS: Of 1,426 samples, 201 from unique patients were ANCA-positive (200 on IIF, 1 on ELISA alone). Thirty-two (45%) of 71 typical ANCA staining patterns were positive for either an anti-MPO or anti-PR3 antibodies, whereas only one (0.8%) of 129 atypical patterns was ELISA-positive, in a patient without systemic vasculitis. Only one (3%) of 34 ELISA-positive samples had a negative IIF-ANCA (1/1,426 patients, 0.07%), and this patient did not have vasculitis. CONCLUSIONS: Concomitant staining on formalin fixation of IIF-positive ethanol-fixed ANCA samples improves the interpretation of ANCA testing and is predictive of vasculitis autoantigens MPO and PR3. PMID- 25125624 TI - Aggressive B-cell lymphomas with translocations involving BCL6 and MYC have distinct clinical-pathologic characteristics. AB - OBJECTIVES: Recently described, aggressive B-cell lymphomas with genetic abnormalities involving MYC and BCL2 have been shown to have a poor prognosis when treated with regimens for diffuse large B-cell lymphomas. Similar data on cases with concurrent MYC and BCL6 translocation are still scant. Moreover, little is known regarding the morphologic and immunophenotypic characteristics of these cases, which further complicates their identification. This study describes six cases of aggressive B-cell lymphoma with translocations involving MYC and BCL6. METHODS: Six cases of large B-cell lymphoma with translocation involving MYC and BCL6 confirmed by fluorescence in situ were identified. The morphologic, immunophenotypic, and clinical features of the cases were examined. RESULTS: All the patients were older women, and in 50% of cases, the presentation was extranodal. In two cases, the liver was involved at presentation. A starry-sky pattern was a constant feature of the cases in which the morphology could be reliably assessed. Five of six cases had an immunophenotype corresponding to the germinal center B cells, and only one was positive for BCL2, an immunophenotype reminiscent of that of Burkitt lymphoma. CONCLUSIONS: B-cell lymphomas with translocations involving MYC and BCL6 have morphologic and immunophenotypic features suggestive of Burkitt lymphoma or gray zone lymphoma, and they tend to be diagnosed mainly in women, often in extranodal locations. PMID- 25125626 TI - Recognition and discrimination of tissue-marking dye color by surgical pathologists: recommendations to avoid errors in margin assessment. AB - OBJECTIVES: A variety of tissue-marking dye (TMD) colors can be used to indicate surgical pathology specimen margins; however, the ability of pathologists to differentiate between specific microscopic margin colors has not been assessed systematically. This study aimed to evaluate pathologists' accuracy in identifying TMD color and determine the least ambiguous combinations of colors for use in surgical pathology. METHODS: Seven colors of TMD were obtained from three manufacturers and applied to excess formalin-fixed uterine tissue. Study blocks contained multiple tissue pieces, each marked with a different color from the same manufacturer. Slides were assessed by eight participants for color and color distinctness of each piece of tissue. RESULTS: Black, green, red, and blue TMDs were accurately identified by most participants, but participants had difficulty identifying violet, orange, and yellow TMDs. Black, green, and blue TMDs were most commonly rated as "confidently discernable." CONCLUSIONS: Pathologists have difficulty identifying and distinguishing certain colors of TMDs. The combined use of certain colors of TMDs (yellow/orange/red, blue/violet, and red/violet) within the same specimen should be avoided to decrease the risk of inaccurately reporting specimen margins. PMID- 25125625 TI - Aberrations of MYC are a common event in B-cell prolymphocytic leukemia. AB - OBJECTIVES: B-cell prolymphocytic leukemia (B-PLL) remains a controversial entity, and its molecular pathogenesis is largely unknown. Patients are older, typically having marked lymphocytosis and splenomegaly in the absence of lymphadenopathy. It is defined as a mature B-cell leukemia with more than 55% circulating prolymphocytes. Leukemic mantle cell lymphoma and chronic lymphocytic leukemia in prolymphocytic transformation must be excluded. METHODS: Case archives were retrospectively reviewed for B-PLL in patients without a previous diagnosis of chronic lymphocytic leukemia or other B-cell neoplasm. RESULTS: We identified six cases of B-PLL with available cytogenetic data, five of which showed evidence of aberrations in MYC. Three cases showed additional signals for the MYC gene by fluorescence in situ hybridization (FISH), and two cases demonstrated t(8;14)MYC/IGH by karyotyping or FISH. High levels of MYC protein expression were detected in all cases tested with MYC aberrations. CONCLUSIONS: These results suggest that deregulation of MYC plays an important role in the pathogenesis of B-PLL and expands the spectrum of B-cell neoplasms associated with aberrations of MYC. PMID- 25125628 TI - Utility of immunofluorescence testing for vascular IgA in adult patients with leukocytoclastic vasculitis. AB - OBJECTIVES: The purpose of this study was to examine the utility of immunofluorescence (IF) testing in patients with leukocytoclastic vasculitis (LCV), particularly with regard to usefulness in the diagnosis of Henoch Schonlein purpura (HSP). METHODS: We retrospectively analyzed the results of IF testing in 96 patients with LCV and compared results with clinical criteria and clinical impression at the time of biopsy by review of the medical record. RESULTS: Sensitivity and specificity of vascular immunoglobulin A (IgA) for the diagnosis of HSP were 0.86 and 0.84, respectively. Positive predictive value was 0.48 and negative predictive value was 0.97. Of the 53 patients with LCV who did not meet clinical criteria for HSP and carried a low clinical suspicion for the disease at the time of biopsy, seven had moderate to strong staining for vascular IgA. Only one of these patients was determined to have HSP. CONCLUSIONS: Our data confirm that vascular IgA is nonspecific and also demonstrate that the utility of IF studies for vasculitis is influenced by the clinical presentation and the clinician's level of suspicion for HSP. Our data show that the clinical features and the overall clinical impression are helpful in selecting which patients are most likely to benefit from IF testing. PMID- 25125627 TI - Significant histologic features differentiating cellular fibroadenoma from phyllodes tumor on core needle biopsy specimens. AB - OBJECTIVES: Cellular fibroepithelial lesions (CFELs) are a heterogeneous group of tumors encompassing cellular fibroadenoma (CFA) and phyllodes tumor (PT). Distinction between the two is challenging on core needle biopsy (CNB) specimens. The objective of this study was to evaluate histologic features that can help distinguish PT from CFA on CNB specimens. METHODS: Records of all patients diagnosed with CFELs on CNB specimens with follow-up excision between January 2002 and December 2012 were retrieved. Histopathologic stromal features were evaluated on CNB specimens, including mitoses per 10 high-power fields (hpf), overgrowth, increased cellularity, fragmentation, adipose tissue infiltration, heterogeneity, subepithelial condensation, and nuclear pleomorphism. RESULTS: Twenty-seven (42.2%) of 64 were diagnosed as PT (24 benign PTs and three borderline PTs) and 37 (57.8%) as CFA on excision. All features except for increased stromal cellularity were statistically significant. The average number of histologic features seen in PT and CFA was 3.9 and 1.4, respectively (odds ratio [OR], 7.27; 95% confidence interval [CI], 2.44-21.69; P = .0004). The average number of mitoses per 10 hpf was 3.0 for PT compared with 0.8 for CFA (OR, 2.14; 95% CI, 1.18-3.86; P = .01). CONCLUSIONS: The presence of mitoses (three or more) and/or total histologic features of three or more on CNB specimens were the most helpful features in predicting PT on excision. PMID- 25125629 TI - Micropapillary pattern and poorly differentiated clusters represent the same biological phenomenon in colorectal cancer: a proposal for a change in terminology. AB - OBJECTIVES: Colorectal carcinomas (CRCs) with a micropapillary pattern and those showing high counts of poorly differentiated clusters (PDCs) are characterized by a higher probability to develop nodal metastases and have a worse prognosis. In light of the morphologic similarity to the micropapillary component, we aimed to verify whether PDCs also display an inverted secretory pattern. METHODS: The immunohistochemical expression of MUC1 and E-cadherin was assessed in a cohort of CRCs with PDCs and compared with that observed in CRCs without PDCs. RESULTS: PDCs in our cases always displayed an inverted MUC1 pattern. In addition, we found abnormal (lost or cytoplasmic) expression of E-cadherin in PDCs. CONCLUSIONS: The altered expression of MUC1 and E-cadherin may account for the aggressive behavior and higher metastatic potential of CRCs with high PDC counts and indicate an epithelial-mesenchymal transition. Our findings suggest that regardless of the morphologic aspect, PDCs and the micropapillary component may reflect the same biological phenomenon in CRCs. Thus, we wonder whether the micropapillary areas should be considered a variant of CRCs or more objectively counted as PDCs to predict prognosis. We also believe that the term PDC better describes the biological phenomena underlying this peculiar morphologic aspect in comparison with the misnomer micropapillary. PMID- 25125630 TI - Performance characteristics of nested polymerase chain reaction vs real-time polymerase chain reaction methods for detecting Mycobacterium tuberculosis complex in paraffin-embedded human tissues. AB - OBJECTIVES: Nucleic acid amplification tests on formalin-fixed, paraffin-embedded (FFPE) tissue specimens enable Mycobacterium tuberculosis complex (MTB) detection and rapid tuberculosis diagnosis in the absence of microbiologic culture tests. We aimed to evaluate the efficacy of different polymerase chain reaction (PCR) methods for detecting Mycobacterium species in FFPE tissues. METHODS: We examined 110 FFPE specimens (56 nonmycobacterial cases, 32 MTB, and 22 nontuberculous mycobacteria [NTM] determined by acid-fast bacilli [AFB] culture) to assess five PCR methods: nested PCR (N-PCR) (Seeplex MTB Nested ACE Detection; Seegene, Seoul, South Korea), an in-house real-time PCR (RT-PCR) method, and three commercial RT-PCR methods (AccuPower MTB RT-PCR [Bioneer, Seoul, Korea], artus M tuberculosis TM PCR [Qiagen, Hilden, Germany], and AdvanSure tuberculosis/NTM RT PCR [LG Life Sciences, Seoul, Korea]). RESULTS: The results of N-PCR, in-house RT PCR, and AdvanSure RT-PCR correlated well with AFB culture results (concordance rates, 94.3%, 87.5%, and 89.5%, respectively). The sensitivity of N-PCR (87.5%) was higher than that of the RT-PCR methods, although these differences were not statistically significant between N-PCR and the in-house and AdvanSure RT-PCR methods (68.8% and 80.0%, respectively). All the PCR methods had high specificities, ranging from 98.2% to 100%. Only two NTM cases were detected by AdvanSure RT-PCR, implying a very low sensitivity. CONCLUSIONS: Well-designed RT PCR and N-PCR can effectively identify MTB in FFPE specimens. PMID- 25125631 TI - Correlation between biological marker expression and fluorine-18 fluorodeoxyglucose uptake in hepatocellular carcinoma. AB - OBJECTIVES: This study investigated the association between several biological markers and fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with hepatocellular carcinoma. METHODS: Forty-two patients with hepatocellular carcinoma who underwent FDG positron emission tomography were included in the study. Tumor sections were immunohistochemically stained for phosphorylated signal transducer and activator of transcription 3 (pSTAT3), hypoxia-inducible factor 1alpha (HIF1alpha), glucose transporter 1 (GLUT1), GLUT2, GLUT3, and GLUT4. RESULTS: The high standardized uptake value (SUV) group showed larger tumor size, more frequent vascular invasion, and poorer differentiation compared with the low SUV group. The high SUV group also showed significantly higher immunohistochemical expression of pSTAT3, HIF1alpha, and GLUT1. The GLUT1 high expression group showed higher alpha-fetoprotein (a tumor marker) and poorer differentiation than did the GLUT1 low-expression group. CONCLUSIONS: Our study indicates that FDG uptake is associated with the expression of pSTAT3, HIF1alpha, and GLUT1 in hepatocellular carcinoma. The expression of these proteins shows a correlation with poor differentiation and vascular invasion. PMID- 25125632 TI - Utility of nine-color, 11-parameter flow cytometry for detection of plasma cell neoplasms: a comparison with bone marrow morphologic findings and concurrent M protein studies in serum and urine. AB - OBJECTIVES: Multiparameter flow cytometry (MFC) is a widely available laboratory platform for the evaluation of plasma cell (PC) neoplasms. We assess the performance of a nine-color MFC assay that uses stain-lyse-fix processing of bone marrow aspirates, minimal wash steps, and high acquisition rates with analysis of up to 1.8 * 10(6) cells. METHODS: MFC results were compared with microscopic examinations, immunohistochemical studies, and serum/urine M-protein measurements from patients with documented or suspected PC neoplasms. RESULTS: Sensitivity exceeded that of microscopic examinations, with or without immunohistochemistry. In patients with PC myeloma, clonal PC detection by MFC fell in concert with M protein levels. However, in a subset of patients, MFC detected clonal PCs after serum/urine studies turned negative. CONCLUSIONS: The nine-color analytic cocktail eliminates duplication of PC gating reagents required for evaluation of the same epitopes using a five- or six-color approach. Fewer analytic cocktails result in lower instrument acquisition times per case, a significant factor for the large data sets required for optimal residual disease assessment. Finally, concurrent analysis of nine epitopes and two light scatter parameters aids detection of residual disease, particularly when it is mixed with polyclonal PCs. PMID- 25125633 TI - Value-based flow testing of chronic lymphoproliferative disorders: a quality improvement project to develop an algorithm to streamline testing and reduce costs. AB - OBJECTIVES: Flow cytometry is essential for the evaluation of lymphoproliferative disorders (LPDs) and their classification. Flow panels routinely incorporate a large array of antibodies, making testing complex and expensive; such panels are likely unnecessary in benign cases or those with straightforward diagnoses. Our aim was to develop a more cost-effective testing strategy based on a retrospective analysis of flow studies for possible LPDs in blood. METHODS: We identified LPD frequencies and types, as well as associated results with patient age and absolute lymphocyte count. RESULTS: We found that the likelihood of LPDs increased with patient age and absolute lymphocyte count and that CD5-positive LPD was the most common LPD diagnosed in our institution (71% of LPDs). Using these data, we devised flow-testing algorithms with a screening test for patients at low risk of disease and a focus on CD5-positive LPD detection, with reflexing as needed. CONCLUSIONS: We project this approach will result in a 40% decrease in antibody utilization. PMID- 25125635 TI - Long-term effects of continuous positive airway pressure on blood pressure and prognosis in hypertensive patients with coronary heart disease and obstructive sleep apnea: a randomized controlled trial. AB - BACKGROUND: Obstructive sleep apnea (OSA) can result in hypertension and significantly increase cardiovascular morbidity and mortality. There are few reports on the long-term effects of continuous positive airway pressure (CPAP) on blood pressure in patients with uncontrolled hypertension with coronary heart disease (CHD) and OSA. METHODS: We conducted a prospective, long-term follow-up study in 83 patients with uncontrolled hypertension, CHD, and OSA randomized to control or CPAP groups. Daytime systolic blood pressure (SBP), diastolic blood pressure (DBP), and severe cardiovascular and cerebrovascular events (SCCEs) were recorded at baseline and follow-up. RESULTS: Seventy-three patients completed the study with a median follow-up of 36 (interquartile range = 24-54) months. The 2 groups had similar characteristics at baseline. CPAP was used for 4.5+/-1.1 hour/night. SBP in the CPAP group was significantly reduced at follow-up (143+/-7 mm Hg vs. 139+/-7 mm Hg, P = 0.04), and SBP decreased by 8mm Hg (95% confidence interval = 1.4-9.9; P = 0.01). Hypertension control was improved (CPAP, 69.4% for CPAP users vs. 43.2% for control subjects; P = 0.02); however, DBP did not reach statistical difference between the groups (81+/-10 mm Hg vs. 79+/-8 mm Hg; P = 0.49). In the CPAP group, the Epworth Sleepiness Scale was markedly reduced (7.0+/-3.4 vs. 3.7+/-2.3; P < 0.001). There was 1 SCCE in the CPAP group (heart failure), and 5 SCCEs in the control group (acute myocardial infarction: 2 (with 1 death); stroke: 3), but there was no significant difference identified. CONCLUSIONS: Long-term CPAP application in uncontrolled hypertension with CHD and OSA significantly reduced daytime SBP, improved hypertension control and daytime sleepiness, and decreased the trend in SCCEs compared with control subjects. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02059993. PMID- 25125636 TI - Association between invasively measured central aortic pressure and left ventricular diastolic function in patients undergoing coronary angiography. AB - BACKGROUND: Because of the invasive nature of catheterization, limited information is available on hemodynamic interaction between the left ventricle and aorta using invasive aortic pressure monitoring. Our aim was to investigate whether parameters of invasively measured central aortic pressure waveform were related with those of left ventricular (LV) diastolic function. METHODS: A total of 153 consecutive stable patients (mean age = 64+/-11 years; 62% men) undergoing invasive coronary angiography (ICA) and transthoracic echocardiography (TTE) were prospectively evaluated. Central aortic pressure waveform was obtained at the ascending aorta using a pigtail catheter before ICA. We calculated pulse pressure (PP), fractional PP (FPP; the ratio of PP to mean pressure), pulsatility index (PI; the ratio of PP to diastolic pressure), augmentation index, wave reflection time, and ejection duration and analyzed their associations with parameters of LV diastolic function in TTE. RESULTS: Most patients (n = 135/153; 88.2%) had significant stenosis (>=50%) of >=1 epicardial coronary arteries. In multiple linear regression analyses, e' and E/e' were significantly correlated with PP, FPP, and PI even after adjustment for potential confounders. There were no significant correlations between other parameters of LV diastolic function, including E/A, deceleration time, and left atrial volume index and parameters of central aortic pressure wave. CONCLUSIONS: Invasively measured central aortic PP, FPP, and PI were independently associated with e' and E/e' in patients undergoing ICA. This result adds to the evidence of a close interaction between LV diastolic function and aortic stiffness in this population. PMID- 25125637 TI - Complete Nucleotide Sequence of pVv01, a P1-Like Plasmid Prophage of Vibrio vulnificus. AB - We report here the 79,263-bp plasmid pVv01 isolated from Vibrio vulnificus. pVv01 is closely related to the Vibrio plasmid p0908 and shows some similarities to phage P1. Unlike p0908, pVv01 represents an intact prophage inducible by mitomycin C. PVv01 phage particles revealed a myoviridal morphology and lytic activity. PMID- 25125638 TI - Draft Genome Sequences of Propionibacterium acnes Type Strain ATCC6919 and Antibiotic-Resistant Strain HL411PA1. AB - Propionibacterium acnes is a major skin commensal and is associated with acne vulgaris, the most common skin disease. Here we report the draft genome sequences of two P. acnes strains, the type strain ATCC6919 and an antibiotic-resistant strain, HL411PA1. PMID- 25125639 TI - Complete genome sequence of porcine epidemic diarrhea virus in Vietnam. AB - Porcine epidemic diarrhea virus (PEDV) has emerged in Vietnam since 2009. Herein, full-length genome sequences are reported for three PEDV isolates from pigs displaying severe diarrhea from farms located in northern and southern provinces of Vietnam. The results provide more understanding of the molecular characteristics of PEDV in Vietnam. PMID- 25125640 TI - Complete Genome Sequence of an Alkane Degrader, Alcanivorax sp. Strain NBRC 101098. AB - Alcanivorax sp. strain NBRC 101098 was isolated from seawater in Japan. Strain NBRC 101098 is able to degrade various types of n-alkanes. Here, we report the complete genome of strain NBRC 101098. PMID- 25125641 TI - Whole-Genome Sequence of Streptococcus suis Serotype 4 Reference Strain 6407. AB - We report here the second complete genome sequence of Streptococcus suis serotype 4 (strain 6407). The genome is 2,292,360 bp in length, covering 2,239 coding sequences, 58 tRNAs, and 4 rRNA loci. PMID- 25125642 TI - Integrated metagenomics and metatranscriptomics analyses of root-associated soil from transgenic switchgrass. AB - The benefits of using transgenic switchgrass with decreased levels of caffeic acid 3-O-methyltransferase (COMT) as biomass feedstock have been clearly demonstrated. However, its effect on the soil microbial community has not been assessed. Here we report metagenomic and metatranscriptomic analyses of root associated soil from COMT switchgrass compared with nontransgenic counterparts. PMID- 25125643 TI - Draft Genome Sequence of Microbacterium sp. Strain CH12i, Isolated from Shallow Groundwater in Cape Hallett, Antarctica. AB - The Antarctic continent is largely covered by an expansive ice sheet, but it harbors diverse terrestrial and aquatic habitats in the coastal ice-free continental margins. Here we present the draft genome of Microbacterium sp. CH12i, which was isolated from hypersaline, alkaline, and nutrient-rich groundwater from Cape Hallett, northern Victoria Land, Antarctica. PMID- 25125644 TI - Draft Genome Sequence of Nonlabens ulvanivorans, an Ulvan-Degrading Bacterium. AB - Here we report the draft genome sequence of the bacterium Nonlabens ulvanivorans, which was recently isolated. To our knowledge, this is the first published genome of a characterized ulvan-degrading bacterium. Revealing the ulvan utilization pathways may provide access to a vast marine biomass source that has yet to be exploited. PMID- 25125645 TI - High-Quality Draft Genomes of Two Vibrio parahaemolyticus Strains Aid in Understanding Acute Hepatopancreatic Necrosis Disease of Cultured Shrimps in Mexico. AB - The high-quality draft genomes of two Vibrio parahaemolyticus strains, one that causes the acute hepatopancreatic necrosis disease (AHPND) in cultured shrimps (FIM-S1708(+)), and another that does not (FIM-S1392(-)) are reported. A chromosome-scale assembly for the FIM-S1392(-) genome is reported here. The analysis of the two genomes gives some clues regarding the genomic differences between the strains. PMID- 25125646 TI - Whole-genome sequences of three symbiotic endozoicomonas strains. AB - Members of the genus Endozoicomonas associate with a wide range of marine organisms. Here, we report on the whole-genome sequencing, assembly, and annotation of three Endozoicomonas type strains. These data will assist in exploring interactions between Endozoicomonas organisms and their hosts, and it will aid in the assembly of genomes from uncultivated Endozoicomonas spp. PMID- 25125647 TI - Whole-Genome Sequence of a Multidrug-Resistant Mycobacterium tuberculosis Beijing Sequence Type 10 Isolate from an Outbreak in Thailand. AB - Infections with the Beijing family of Mycobacterium tuberculosis occur worldwide and are endemic in Asian countries. We present the draft genome sequence of DS6701, a multidrug-resistant M. tuberculosis Beijing strain of sequence type 10. The isolate is a representative of strains isolated from a multidrug-resistant tuberculosis outbreak in Thailand. PMID- 25125648 TI - Draft Genome Sequence of Burkholderia sordidicola S170, a Potential Plant Growth Promoter Isolated from Coniferous Forest Soil in the Czech Republic. AB - Burkholderia species are key players in the accumulation of carbon from cellulose decomposition in coniferous forest ecosystems. We report here the draft genome of Burkholderia sordidicola strain S170, containing features associated with known genes involved in plant growth promotion, the biological control of plant diseases, and green remediation technologies. PMID- 25125649 TI - Draft Genome Sequence of Haloferax sp. Strain ATB1, Isolated from a Semi-Arid Region in the Brazilian Caatinga. AB - Organisms in the Haloferax genus are extreme halophiles that grow in environments with pH values between 4 and 12, and temperatures between 0 degrees C and 60 degrees C. In the present study, a draft of the first Haloferax sp. strain ATB1 genome isolated from the region of Cariri (in Paraiba State, Brazil) is presented. PMID- 25125650 TI - A Gapless, Unambiguous Genome Sequence of the Enterohemorrhagic Escherichia coli O157:H7 Strain EDL933. AB - Escherichia coli EDL933 is the prototypic strain for enterohemorrhagic E. coli serotype O157:H7, associated with deadly food-borne outbreaks. Because the publicly available sequence of the EDL933 genome has gaps and >6,000 ambiguous base calls, we here present an updated high-quality, unambiguous genome sequence with no assembly gaps. PMID- 25125651 TI - Draft Genome Sequence of an Atypical Strain of Streptococcus pneumoniae Isolated from a Respiratory Infection. AB - Next-generation sequencing was used to investigate an unknown clinical respiratory infection. This new strain of Streptococcus pneumoniae, ASVL_JC_0001, was isolated from a clinical specimen from a patient with bronchitis and pulmonary inflammation. The draft genome sequence, obtained with an Illumina MiSeq sequencing system, consists of 83 large contigs, a total of 2,092,532 bp long, and has a GC content of 40.3%. PMID- 25125652 TI - Draft Genome Sequence of Staphylococcus chromogenes Strain MU 970, Isolated from a Case of Chronic Bovine Mastitis. AB - Coagulase-negative staphylococcal species are a common cause of subclinical bovine mastitis, with Staphylococcus chromogenes being one of the most frequently identified species in these cases. The draft genome sequence of an S. chromogenes isolate (MU 970) recovered from the milk of a cow with a chronic intramammary infection is reported here. PMID- 25125653 TI - Draft Genome Sequence of Rifamycin Derivatives Producing Amycolatopsis mediterranei Strain DSM 46096/S955. AB - Amycolatopsis mediterranei DSM 46096 produces antibiotics of the rifamycin family, 27-demethoxy-27-hydroxyrifamycin B, 25-desacetyl-27-demethoxy-27 hydroxyrifamycin, and 27-demethoxy-27-hydroxyrifamycin SV, which are effective against Gram-negative bacteria. Here, we present the draft genome of A. mediterranei 46096 (approx. 10.2 Mbp) having 104 contigs with a GC content of 71.3% and 9,382 coding sequences. PMID- 25125654 TI - Draft Genome Sequence of Haloalkaliphilic Exiguobacterium sp. Strain AB2 from Manleluag Ophiolitic Spring, Philippines. AB - Exiguobacterium sp. AB2 is a haloalkaliphilic bacterium isolated from a hyperalkaline spring in Manleluag, Pangasinan, Philippines. Sequencing of bacterial DNA assembled a 2.85 MB draft genome. Analysis suggests the presence of genes for tolerance to stresses such as elevated pH and salt concentrations and toxic metals. PMID- 25125655 TI - EGFR blockade enriches for lung cancer stem-like cells through Notch3-dependent signaling. AB - Mutations in the epidermal growth factor receptor (EGFR) are the most common actionable genetic abnormalities yet discovered in lung cancer. However, targeting these mutations with kinase inhibitors is not curative in advanced disease and has yet to demonstrate an impact on potentially curable, early-stage disease, with some data suggesting adverse outcomes. Here, we report that treatment of EGFR-mutated lung cancer cell lines with erlotinib, while showing robust cell death, enriches the ALDH(+) stem-like cells through EGFR-dependent activation of Notch3. In addition, we demonstrate that erlotinib treatment increases the clonogenicity of lung cancer cells in a sphere-forming assay, suggesting increased stem-like cell potential. We demonstrate that inhibition of EGFR kinase activity leads to activation of Notch transcriptional targets in a gamma secretase inhibitor-sensitive manner and causes Notch activation, leading to an increase in ALDH high(+) cells. We also find a kinase-dependent physical association between the Notch3 and EGFR receptors and tyrosine phosphorylation of Notch3. This could explain the worsened survival observed in some studies of erlotinib treatment at early-stage disease, and suggests that specific dual targeting might overcome this adverse effect. PMID- 25125657 TI - Cytokine-like molecule CCDC134 contributes to CD8+ T-cell effector functions in cancer immunotherapy. AB - CCDC134 is a poorly characterized secreted protein that may act as an immune cytokine. Here, we show that CCDC134 is differentially expressed on resting and activated immune cells and that it promotes CD8(+) T-cell activation, proliferation, and cytotoxicity by augmenting expression of the T-cell effector molecules IFNgamma, TNFalpha, granzyme B, and perforin. CCDC134 facilitated infiltration of CD8(+) T cells with enhanced cytolytic activity into tumors, demonstrating strong antitumor effects in a CD8(+) T-cell-dependent manner. Mechanistically, in CD8(+) T cells, exposure to CCDC134 promoted cell proliferation through the JAK3-STAT5 pathway, a classic feature of many cytokines of the common gamma-chain (gamma(c)) cytokine receptor family. Overall, our results provide evidence that CCDC134 may serve as a member of the gamma(c) cytokine family and illustrate its potent antitumor effects by augmenting CD8(+) T-cell-mediated immunity. PMID- 25125656 TI - Vaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment. AB - Eradicating malignant tumors by vaccine-elicited host immunity remains a major medical challenge. To date, correlates of immune protection remain unknown for malignant mesothelioma. In this study, we demonstrated that antigen-specific CD8(+) T-cell immune response correlates with the elimination of malignant mesothelioma by a model PD-1-based DNA vaccine. Unlike the nonprotective tumor antigen WT1-based DNA vaccines, the model vaccine showed complete and long lasting protection against lethal mesothelioma challenge in immunocompetent BALB/c mice. Furthermore, it remained highly immunogenic in tumor-bearing animals and led to therapeutic cure of preexisting mesothelioma. T-cell depletion and adoptive transfer experiments revealed that vaccine-elicited CD8(+) T cells conferred to the protective efficacy in a dose-dependent way. Also, these CD8(+) T cells functioned by releasing inflammatory IFNgamma and TNFalpha in the vicinity of target cells as well as by initiating TRAIL-directed tumor cell apoptosis. Importantly, repeated DNA vaccinations, a major advantage over live vectored vaccines with issues of preexisting immunity, achieve an active functional state, not only preventing the rise of exhausted PD-1(+) and Tim-3(+) CD8(+) T cells but also suppressing tumor-induced myeloid-derived suppressive cells and Treg cells, with the frequency of antigen-specific CD8(+) T cells inversely correlating with tumor mass. Our results provide new insights into quantitative and qualitative requirements of vaccine-elicited functional CD8(+) T cells in cancer prevention and immunotherapy. PMID- 25125659 TI - AXL inhibition sensitizes mesenchymal cancer cells to antimitotic drugs. AB - Molecularly targeted drug therapies have revolutionized cancer treatment; however, resistance remains a major limitation to their overall efficacy. Epithelial-to-mesenchymal transition (EMT) has been linked to acquired resistance to tyrosine kinase inhibitors (TKI), independent of mutational resistance mechanisms. AXL is a receptor tyrosine kinase associated with EMT that has been implicated in drug resistance and has emerged as a candidate therapeutic target. Across 643 human cancer cell lines that were analyzed, elevated AXL was strongly associated with a mesenchymal phenotype, particularly in triple-negative breast cancer and non-small cell lung cancer. In an unbiased screen of small-molecule inhibitors of cancer-relevant processes, we discovered that AXL inhibition was specifically synergistic with antimitotic agents in killing cancer cells that had undergone EMT and demonstrated associated TKI resistance. However, we did not find that AXL inhibition alone could overcome acquired resistance to EGFR TKIs in the EMT setting, as previously reported. These findings reveal a novel cotreatment strategy for tumors displaying mesenchymal features that otherwise render them treatment refractory. PMID- 25125658 TI - NQO1 suppresses NF-kappaB-p300 interaction to regulate inflammatory mediators associated with prostate tumorigenesis. AB - NADPH reductase NAD(P)H: quinone oxidoreductase 1 (NQO1) is needed to maintain a cellular pool of antioxidants, and this enzyme may contribute to tumorigenesis on the basis of studies in NQO1-deficient mice. In this work, we sought deeper insights into how NQO1 contributes to prostate carcinogenesis, a setting in which oxidative stress and inflammation are established contributors to disease development and progression. In the TRAMP mouse model of prostate cancer, NQO1 was highly expressed in tumor cells. NQO1 silencing in prostate cancer cells increased levels of nuclear IKKalpha and NF-kappaB while decreasing the levels of p53, leading to interactions between NF-kappaB and p300 that reinforce survival signaling. Gene expression analysis revealed upregulation of a set of immune associated transcripts associated with inflammation and tumorigenesis in cells in which NQO1 was attenuated, with IL8 confirmed functionally in cell culture as one key NQO1-supported cytokine. Notably, NQO1-silenced prostate cancer cells were more resistant to androgen deprivation. Furthermore, NQO1 inhibition increased migration, including under conditions of androgen deprivation. These results reveal a molecular link between NQO1 expression and proinflammatory cytokine signaling in prostate cancer. Furthermore, our results suggest that altering redox homeostasis through NQO1 inhibition might promote androgen-independent cell survival via opposing effects on NF-kappaB and p53 function. PMID- 25125660 TI - PAK1 tyrosine phosphorylation is required to induce epithelial-mesenchymal transition and radioresistance in lung cancer cells. AB - The p21-activated Ser/Thr kinase 1 (PAK1) kinase has an essential role in tumorigenesis and cell survival in many cancers, but its regulation is not fully understood. In this study, we showed that in response to irradiation of lung cancer cells, PAK1 was upregulated, tyrosine phosphorylated, and translocated to the nucleus. Tyrosine phosphorylation relied upon JAK2 kinase activity and was essential for PAK1 protein stability and binding to Snail. This radiation-induced JAK2-PAK1-Snail signaling pathway increased epithelial-mesenchymal transition (EMT) by regulating epithelial and mesenchymal cell markers. Notably, JAK2 inhibitors mediated radiosensitization and EMT blockade in a mouse xenograft model of lung cancer. Taken together, our findings offered evidence that JAK2 phosphorylates and stabilizes functions of PAK1 that promote EMT and radioresistance in lung cancer cells, with additional implications for the use of JAK2 inhibitors as radiosensitizers in lung cancer treatment. PMID- 25125661 TI - Transcriptional dynamics in colorectal carcinogenesis: new insights into the role of c-Myc and miR17 in benign to cancer transformation. AB - Colorectal cancer develops in a sequential, evolutionary process, leading to a heterogenic tumor. Comprehensive molecular studies of colorectal cancer have been previously performed; still, the process of carcinogenesis is not fully understood. We utilized gene expression patterns from 94 samples including normal, adenoma, and adenocarcinoma colon biopsies and performed a coexpression network analysis to determine gene expression trajectories of 8,000 genes across carcinogenesis. We found that the majority of gene expression changes occur in the transition from normal tissue to adenoma. The upregulated genes, known to be involved in cellular proliferation, included c-Myc along with its targets. In a cellular model system, we show that physiologic upregulation of c-Myc can lead to cellular proliferation without DNA replication stress. Our analysis also found that carcinogenesis involves a progressive downregulation of genes that are markers of colonic tissue and propose that this reflects a perturbed differentiation of colon cells during carcinogenesis. The analysis of miRNAs targets pointed toward the involvement of miR17 in the regulation of colon cell differentiation. Finally, we found that copy-number variations (CNV) enriched in colon adenocarcinoma tend to occur in genes whose expression changes already in adenoma, with deletions occurring in genes downregulated and duplications in genes upregulated in adenomas. We suggest that the CNVs are selected to reinforce changes in gene expression, rather than initiate them. Together, these findings shed new light into the molecular processes that underlie the transformation of colon tissue from normal to cancer and add a temporal context that has been hitherto lacking. PMID- 25125662 TI - Translesion polymerase eta is upregulated by cancer therapeutics and confers anticancer drug resistance. AB - DNA repair processes are a key determinant of the sensitivity of cancer cells to DNA-damaging chemotherapeutics, which may induce certain repair genes as a mechanism to promote resistance. Here, we report the results of a screen for repair genes induced in cancer cells treated with DNA crosslinking agents, which identified the translesion polymerase eta (PolH) as a p53-regulated target acting as one defense against interstrand crosslink (ICL)-inducing agents. PolH was induced by fotemustine, mafosfamide, and lomustine in breast cancer, glioma, and melanoma cells in vitro and in vivo, with similar inductions observed in normal cells such as lymphocytes and diploid fibroblasts. PolH contributions to the protection against ICL-inducing agents were evaluated by its siRNA-mediated attenuation in cells, which elevated sensitivity to these drugs in all tumor cell models. Conversely, PolH overexpression protected cancer cells against these drugs. PolH attenuation reduced repair of ICL lesions as measured by host cell reactivation assays and enhanced persistence of gammaH2AX foci. Moreover, we observed a strong accumulation of PolH in the nucleus of drug-treated cells along with direct binding to damaged DNA. Taken together, our findings implicated PolH in ICL repair as a mechanism of cancer drug resistance and normal tissue protection. PMID- 25125663 TI - Evaluation of a metal artifacts reduction algorithm applied to postinterventional flat panel detector CT imaging. AB - BACKGROUND AND PURPOSE: Flat panel detector CT images are degraded by streak artifacts caused by radiodense implanted materials such as coils or clips. A new metal artifacts reduction prototype algorithm has been used to minimize these artifacts. The application of this new metal artifacts reduction algorithm was evaluated for flat panel detector CT imaging performed in a routine clinical setting. MATERIALS AND METHODS: Flat panel detector CT images were obtained from 59 patients immediately following cerebral endovascular procedures or as surveillance imaging for cerebral endovascular or surgical procedures previously performed. The images were independently evaluated by 7 physicians for metal artifacts reduction on a 3-point scale at 2 locations: immediately adjacent to the metallic implant and 3 cm away from it. The number of visible vessels before and after metal artifacts reduction correction was also evaluated within a 3-cm radius around the metallic implant. RESULTS: The metal artifacts reduction algorithm was applied to the 59 flat panel detector CT datasets without complications. The metal artifacts in the reduction-corrected flat panel detector CT images were significantly reduced in the area immediately adjacent to the implanted metal object (P = .05) and in the area 3 cm away from the metal object (P = .03). The average number of visible vessel segments increased from 4.07 to 5.29 (P = .1235) after application of the metal artifacts reduction algorithm to the flat panel detector CT images. CONCLUSIONS: Metal artifacts reduction is an effective method to improve flat panel detector CT images degraded by metal artifacts. Metal artifacts are significantly decreased by the metal artifacts reduction algorithm, and there was a trend toward increased vessel-segment visualization. PMID- 25125664 TI - High-resolution CT findings in children with a normal pinna or grade I microtia and unilateral mild stenosis of the external auditory canal. AB - SUMMARY: A subset of patients presents with unilateral conductive hearing loss, a normal pinna or grade I microtia, and mild external auditory canal stenosis. The physical findings of microtia and a small external canal are commonly absent or subtle in this group of patients, who are being commonly referred for imaging to evaluate isolated conductive hearing loss. We present a case series of patients with unilateral conductive hearing loss and characteristic ossicular abnormalities, commonly anterior fixation of the malleus. All patients had a significantly increased distance from the cochlear promontory to the handle of the malleus and an abnormal incudostapedial angle, indicative of an abnormal ossicular position and/or morphology. Successful surgical reconstruction of the ossicular chain was attempted and accomplished in 3 patients. PMID- 25125665 TI - One-year MR angiographic and clinical follow-up after intracranial mechanical thrombectomy using a stent retriever device. AB - BACKGROUND AND PURPOSE: Little is known about the consequences of arterial wall damage that may be due to mechanical endovascular thrombectomy. Our aim was to perform 1-year MR angiographic and clinical follow-up of patients treated with mechanical endovascular thrombectomy using the Solitaire device. MATERIALS AND METHODS: Patients with stroke treated between August 2010 and July 2012 were prospectively evaluated with a minimum follow-up of 1 year after mechanical endovascular thrombectomy. Angiographic follow-up was performed on a 3T MR imaging scanner and included intracranial artery TOF MRA and supra-aortic artery gadolinium-enhanced MRA. Images were assessed to detect arterial abnormalities (stenosis, occlusion, dilation) and were compared with the final post-mechanical endovascular thrombectomy run to differentiate delayed and pre-existing abnormalities. Clinical evaluation was performed with the mRS and the 36-Item Short-Form Health Survey questionnaire quality-of-life scale. RESULTS: Thirty nine patients were angiographically assessed at the mean term of 19 +/- 4 months. MRA showed intracranial artery abnormalities in 10 patients, including 5 delayed intracranial artery abnormalities in 4 patients (4 stenoses and 1 dilation), 4 cases of pre-existing intracranial artery stenosis, and 2 occlusions. Pre existing etiologic cervical artery stenosis or occlusion was observed in 2 patients. All these patients remained asymptomatic during the follow-up period. A significant clinical improvement was observed at 1-year follow-up in comparison with 3-month follow-up (P < .0001), with a good outcome achieved in 62.5% of patients and an acceptable quality of life restored. CONCLUSIONS: One-year follow up identifies delayed asymptomatic arterial abnormalities in patients treated with the Solitaire device. PMID- 25125666 TI - Surpass flow diverter in the treatment of intracranial aneurysms: a prospective multicenter study. AB - BACKGROUND AND PURPOSE: Incomplete occlusion and recanalization of large and wide neck brain aneurysms treated by endovascular therapy remains a challenge. We present preliminary clinical and angiographic results of an experimentally optimized Surpass flow diverter for treatment of intracranial aneurysms in a prospective, multicenter, nonrandomized, single-arm study. MATERIALS AND METHODS: At 24 centers, 165 patients with 190 intracranial aneurysms of the anterior and posterior circulations were enrolled. The primary efficacy end point was the percentage of intracranial aneurysms with 100% occlusion on 6-month DSA. The primary safety end point was neurologic death and any stroke through a minimum follow-up of 6 months. RESULTS: Successful flow-diverter delivery was achieved in 161 patients with 186 aneurysms (98%); the mean number of devices used per aneurysm was 1.05. Clinical follow-up (median, 6 months) of 150 patients (93.2%), showed that the primary safety end point occurred in 18 subjects. Permanent neurologic morbidity and mortality were 6% and 2.7%, respectively. Morbidity occurred in 4% and 7.4% of patients treated for aneurysms of the anterior and posterior circulation, respectively. Neurologic death during follow-up was observed in 1.6% and 7.4% of patients with treated intracranial aneurysms of the anterior and posterior circulation, respectively. Ischemic stroke at <=30 days, SAH at <=7 days, and intraparenchymal hemorrhage at <=7 days were encountered in 3.7%, 2.5%, and 2.5% of subjects, respectively. No disabling ischemic strokes at >30 days or SAH at >7 days occurred. New or worsening cranial nerve deficit was observed in 2.7%. Follow-up angiography available in 158 (86.8%) intracranial aneurysms showed 100% occlusion in 75%. CONCLUSIONS: Clinical outcomes of the Surpass flow diverter in the treatment of intracranial aneurysms show a safety profile that is comparable with that of stent-assisted coil embolization. Angiographic results showed a high rate of intracranial aneurysm occlusion. PMID- 25125667 TI - Middle cerebral artery stenosis in patients with acute ischemic stroke and TIA in Israel. AB - BACKGROUND AND PURPOSE: Middle cerebral artery stenosis is not frequent but a well-established cause of first and recurrent ischemic stroke. Our aim was to investigate middle cerebral artery stenosis in the biethnic (Jewish and Arab) population of patients with acute ischemic stroke and transient ischemic attack in northern Israel. MATERIALS AND METHODS: The study population included 1344 patients from the stroke data registry who had been hospitalized in the neurologic department because of acute ischemic stroke (1041) or TIA (303) and had undergone transcranial Doppler sonographic examination during the hospitalization. RESULTS: Of the 1344 patients, 120 (8.9%) were found to have MCA stenosis. The patients with intracranial stenosis were older and had more vascular risk factors (hypertension, diabetes, and hyperlipidemia) and vascular diseases (ischemic heart and peripheral vascular disease) than those without intracranial stenosis. Logistic regression analysis revealed that diabetes (P = .002) and peripheral vascular disease (P = .01), but not ethnicity, were independent and significant predictors for the presence of MCA stenosis. CONCLUSIONS: An independent and significant correlation was found between MCA stenosis and vascular risk factors (diabetes mellitus) and vascular diseases, thus emphasizing the similarity of intracranial MCA stenosis and other vascular diseases originating from atherosclerosis. There was no influence of ethnicity on intracranial stenosis in our population. PMID- 25125669 TI - Expanding minimally invasive innovation to complex mitral reoperations. PMID- 25125670 TI - Nitric oxide (NO): an emerging target for the treatment of glaucoma. AB - The predominant risk factor for the progression of glaucoma is an increase in IOP, mediated via a reduction in aqueous outflow through the conventional (trabecular meshwork and Schlemm's canal) outflow pathway. Current IOP lowering pharmacological strategies target the uveoscleral (nonconventional) outflow pathway or aqueous humor production; however, to date no therapy that primarily targets the conventional pathway exists. Nitric oxide (NO) is an intracellular signaling molecule produced by endogenous NO synthases, well-known for its key role in vasodilation, through its action on smooth muscle cells. Under physiological conditions, NO mediates a multitude of diverse ocular effects, including maintenance of IOP. Nitric oxide donors have been shown to mediate IOP lowering effects in both preclinical models and clinical studies, primarily through cell volume and contractility changes in the conventional outflow tissues. This review is focused on evaluating the current knowledge of the role and mechanism of action of endogenous NO and NO donors in IOP regulation. Data on key additional functions of NO in glaucoma pathology (i.e., ocular blood flow and effects on optic neuropathy) are also summarized. The potential for future therapeutic application of NO in the treatment of glaucoma is then discussed. PMID- 25125671 TI - Choroidal thickness and axial length. PMID- 25125672 TI - Author response: Choroidal thickness and axial length. PMID- 25125673 TI - Anterior segment parameters during unilateral acute primary angle closure. PMID- 25125674 TI - Author response: Anterior segment parameters during unilateral acute primary angle closure. PMID- 25125676 TI - Aspergillus fumigatus harbouring the sole Y121F mutation shows decreased susceptibility to voriconazole but maintained susceptibility to itraconazole and posaconazole. AB - OBJECTIVES: Voriconazole, itraconazole and posaconazole are members of the azole family and widely used for the treatment of aspergillosis. They act by inhibiting the activity of the fungal Cyp51A enzyme. The emergence of environmental azole resistant Aspergillus fumigatus strains raises major concerns for human health. METHODS: Recently, a new cyp51A-mediated resistance mechanism (namely TR46/Y121F/T289A) was described in clinical samples and patient-frequented environmental sites. In an azole-naive patient, we isolated an A. fumigatus strain that was not susceptible to voriconazole but was susceptible to itraconazole and posaconazole. RESULTS: A molecular analysis indicated a single Y121F substitution without the TR46 or T289A alterations, which to our knowledge has never been reported. Structure modelling and molecular dynamics offered an explanation for the resistance profile consistent with the structural differences between the three azoles. CONCLUSIONS: Taken together, these observations suggest an original mechanism conferring resistance to azoles mediated by cyp51A of environmental origin. This uncommon susceptibility pattern might represent a 'missing link' between the wild-type A. fumigatus and the fully azole-resistant strain harbouring the TR46/Y121F/T289A mutations. PMID- 25125677 TI - Vancomycin plus ceftaroline shows potent in vitro synergy and was successfully utilized to clear persistent daptomycin-non-susceptible MRSA bacteraemia. PMID- 25125675 TI - Inhibition of endoglin-GIPC interaction inhibits pancreatic cancer cell growth. AB - Endoglin, a 180-kDa disulfide-linked homodimeric transmembrane receptor protein mostly expressed in tumor-associated endothelial cells, is an endogenous binding partner of GAIP-interacting protein, C terminus (GIPC). Endoglin functions as a coreceptor of TbetaRII that binds TGFbeta and is important for vascular development, and consequently has become a compelling target for antiangiogenic therapies. A few recent studies in gastrointestinal stromal tumor (GIST), breast cancer, and ovarian cancer, however, suggest that endoglin is upregulated in tumor cells and is associated with poor prognosis. These findings indicate a broader role of endoglin in tumor biology, beyond angiogenic effects. The goal of our current study is to evaluate the effects of targeting endoglin in pancreatic cancer both in vitro and in vivo. We analyzed the antiproliferative effect of both RNAi-based and peptide ligand-based inhibition of endoglin in pancreatic cancer cell lines, the latter yielding a GIPC PDZ domain-targeting lipopeptide with notable antiproliferative activity. We further demonstrated that endoglin inhibition induced a differentiation phenotype in the pancreatic cancer cells and sensitized them against conventional chemotherapeutic drug gemcitabine. Most importantly, we have demonstrated the antitumor effect of both RNAi-based and competitive inhibitor-based blocking of endoglin in pancreatic cancer xenograft models in vivo. To our knowledge, this is the first report exploring the effect of targeting endoglin in pancreatic cancer cells. PMID- 25125678 TI - Monotherapy versus combination therapy for sepsis due to multidrug-resistant Acinetobacter baumannii: analysis of a multicentre prospective cohort--authors' response. PMID- 25125679 TI - Improvement in bone mineral density after switching from tenofovir to abacavir in HIV-1-infected patients with low bone mineral density: two-centre randomized pilot study (OsteoTDF study). AB - BACKGROUND: Tenofovir has been associated with a decrease in bone mineral density (BMD). However, data on changes in BMD after discontinuing tenofovir are lacking. METHODS: We performed a two-centre randomized pilot study in virologically suppressed HIV-infected patients receiving tenofovir with osteopenia/osteoporosis (OsteoTDF study, ClinicalTrials.gov number NCT 01153217). Fifty-four patients were randomly assigned to switch from tenofovir to abacavir (n = 26) or to continue with tenofovir (n = 28). Changes in lumbar and total hip BMD were evaluated at Week 48 from baseline. RESULTS: Five patients discontinued the study (three from the tenofovir group and two from the abacavir group). No significant differences were detected between the groups at Week 48 (P = 0.229 for total hip and P = 0.312 for lumbar spine). However, hip BMD improved by 2.1% (95% CI -0.6 to 4.7) (P = 0.043) in the abacavir group and 0.7% (95% CI -0.9 to 2.4) (P = 0.372) in the tenofovir group. Lumbar spine BMD varied by -0.7% (95% CI -3.8 to 3.3) (P <= 0.001) in the abacavir group and -1.2% (95% CI -3.8 to 0.4) (P < 0.001) in the tenofovir group. CONCLUSIONS: Switching from tenofovir to abacavir led to a slight improvement in femoral BMD although no differences were detected between groups. Larger studies are necessary before firm recommendations can be made on the discontinuation of tenofovir in patients with a low BMD. PMID- 25125682 TI - NSAID use reduces breast cancer recurrence in overweight and obese women: role of prostaglandin-aromatase interactions. AB - Obesity is associated with a worse breast cancer prognosis and elevated levels of inflammation, including greater cyclooxygenase-2 (COX-2) expression and activity in adipose-infiltrating macrophages. The product of this enzyme, the proinflammatory eicosanoid prostaglandin E2 (PGE2), stimulates adipose tissue aromatase expression and subsequent estrogen production, which could promote breast cancer progression. This study demonstrates that daily use of a nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 activity, is associated with reduced estrogen receptor alpha (ERalpha)-positive breast cancer recurrence in obese and overweight women. Retrospective review of data from ERalpha-positive patients with an average body mass index of >30 revealed that NSAID users had a 52% lower recurrence rate and a 28-month delay in time to recurrence. To examine the mechanisms that may be mediating this effect, we conducted in vitro studies that utilized sera from obese and normal-weight patients with breast cancer. Exposure to sera from obese patients stimulated greater macrophage COX-2 expression and PGE2 production. This was correlated with enhanced preadipocyte aromatase expression following incubation in conditioned media (CM) collected from the obese-patient, sera-exposed macrophages, an effect neutralized by COX-2 inhibition with celecoxib. In addition, CM from macrophage/preadipocyte cocultures exposed to sera from obese patients stimulated greater breast cancer cell ERalpha activity, proliferation, and migration compared with sera from normal-weight patients, and these differences were eliminated or reduced by the addition of an aromatase inhibitor during CM generation. Prospective studies designed to examine the clinical benefit of NSAID use in obese patients with breast cancer are warranted. PMID- 25125681 TI - AEG-1 regulates retinoid X receptor and inhibits retinoid signaling. AB - Retinoid X receptor (RXR) regulates key cellular responses such as cell growth and development, and this regulation is frequently perturbed in various malignancies, including hepatocellular carcinoma (HCC). However, the molecule(s) that physically govern this deregulation are mostly unknown. Here, we identified RXR as an interacting partner of astrocyte-elevated gene-1 (AEG-1)/metadherin (MTDH), an oncogene upregulated in all cancers. Upon interaction, AEG-1 profoundly inhibited RXR/retinoic acid receptor (RAR)-mediated transcriptional activation. Consequently, AEG-1 markedly protected HCC and acute myelogenous leukemia (AML) cells from retinoid- and rexinoid-induced cell death. In nontumorigenic cells and primary hepatocytes, AEG-1/RXR colocalizes in the nucleus in which AEG-1 interferes with recruitment of transcriptional coactivators to RXR, preventing transcription of target genes. In tumor cells and AEG-1 transgenic hepatocytes, overexpressed AEG-1 entraps RXR in cytoplasm, precluding its nuclear translocation. In addition, ERK, activated by AEG-1, phosphorylates RXR that leads to its functional inactivation and attenuation of ligand-dependent transactivation. In nude mice models, combination of all-trans retinoic acid (ATRA) and AEG-1 knockdown synergistically inhibited growth of human HCC xenografts. The present study establishes AEG-1 as a novel homeostatic regulator of RXR and RXR/RAR that might contribute to hepatocarcinogenesis. Targeting AEG-1 could sensitize patients with HCC and AML to retinoid- and rexinoid-based therapeutics. PMID- 25125683 TI - Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment. AB - Eph receptor tyrosine kinases are critical for cell-cell communication during normal and oncogenic tissue patterning and tumor growth. Somatic mutation profiles of several cancer genomes suggest EphA3 as a tumor suppressor, but its oncogenic expression pattern and role in tumorigenesis remain largely undefined. Here, we report unexpected EphA3 overexpression within the microenvironment of a range of human cancers and mouse tumor xenografts where its activation inhibits tumor growth. EphA3 is found on mouse bone marrow-derived cells with mesenchymal and myeloid phenotypes, and activation of EphA3(+)/CD90(+)/Sca1(+) mesenchymal/stromal cells with an EphA3 agonist leads to cell contraction, cell cell segregation, and apoptosis. Treatment of mice with an agonistic alpha-EphA3 antibody inhibits tumor growth by severely disrupting the integrity and function of newly formed tumor stroma and microvasculature. Our data define EphA3 as a novel target for selective ablation of the tumor microenvironment and demonstrate the potential of EphA3 agonists for anticancer therapy. PMID- 25125684 TI - Enteric neural progenitors are more efficient than brain-derived progenitors at generating neurons in the colon. AB - Gut motility disorders can result from an absent, damaged, or dysfunctional enteric nervous system (ENS). Cell therapy is an exciting prospect to treat these enteric neuropathies and restore gut motility. Previous studies have examined a variety of sources of stem/progenitor cells, but the ability of different sources of cells to generate enteric neurons has not been directly compared. It is important to identify the source of stem/progenitor cells that is best at colonizing the bowel and generating neurons following transplantation. The aim of this study was to compare the ability of central nervous system (CNS) progenitors and ENS progenitors to colonize the colon and differentiate into neurons. Genetically labeled CNS- and ENS-derived progenitors were cocultured with aneural explants of embryonic mouse colon for 1 or 2.5 wk to assess their migratory, proliferative, and differentiation capacities, and survival, in the embryonic gut environment. Both progenitor cell populations were transplanted in the postnatal colon of mice in vivo for 4 wk before they were analyzed for migration and differentiation using immunohistochemistry. ENS-derived progenitors migrated further than CNS-derived cells in both embryonic and postnatal gut environments. ENS-derived progenitors also gave rise to more neurons than their CNS-derived counterparts. Furthermore, neurons derived from ENS progenitors clustered together in ganglia, whereas CNS-derived neurons were mostly solitary. We conclude that, within the gut environment, ENS-derived progenitors show superior migration, proliferation, and neuronal differentiation compared with CNS progenitors. PMID- 25125685 TI - Transforming consumer health informatics through a patient work framework: connecting patients to context. AB - Designing patient-centered consumer health informatics (CHI) applications requires understanding and creating alignment with patients' and their family members' health-related activities, referred to here as 'patient work'. A patient work approach to CHI draws on medical social science and human factors engineering models and simultaneously attends to patients, their family members, activities, and context. A patient work approach extends existing approaches to CHI design that are responsive to patients' biomedical realities and personal skills and behaviors. It focuses on the embeddedness of patients' health management in larger processes and contexts and prioritizes patients' perspectives on illness management. Future research is required to advance (1) theories of patient work, (2) methods for assessing patient work, and (3) techniques for translating knowledge of patient work into CHI application design. Advancing a patient work approach within CHI is integral to developing and deploying consumer-facing technologies that are integrated with patients' everyday lives. PMID- 25125686 TI - Reducing caregiver stress with internet-based interventions: a systematic review of open-label and randomized controlled trials. AB - OBJECTIVE: The high level of stress associated with caring for others with medical conditions has been recognized for some time. Reducing caregiver stress can improve caregiver quality of life as well as improve the care they provide to loved ones. This systematic review assesses the effectiveness of internet-based interventions to decrease caregiver stress. MATERIALS AND METHODS: A comprehensive literature search of Ovid MEDLINE (1946-2013), Embase (1988-2013), PsycINFO (1987-2013), and CINAHL was conducted using terms related to caregiver and internet-based interventions. Internet-based interventions involving informal caregivers in an open-label or randomized controlled trial setting were included. A pair of raters independently reviewed all published abstracts. Data regarding participants, interventions, and outcomes were extracted and, for randomized trials, methodology quality was also reviewed. RESULTS: Eight open-label trials met the review criteria: three showed positive benefit in reducing caregiver stress, four were partially positive (some outcomes positive, others negative), and one was a negative study. Sixteen randomized trials met the review criteria: six showed positive benefit, five were partially positive, and five were negative. There were no clear patterns as to the variables (such as study duration and complexity of intervention) associated with better outcomes, although earlier studies typically had more negative outcomes. DISCUSSION: Internet-based interventions were mostly effective in reducing aspects of caregiver stress and improving their well-being. Further studies to assess outcomes for caregivers and their recipients' health, different technology delivery methods, and the cost of such interventions are needed. PMID- 25125687 TI - Registration of whole immunohistochemical slide images: an efficient way to characterize biomarker colocalization. AB - BACKGROUND AND OBJECTIVE: Extracting accurate information from complex biological processes involved in diseases, such as cancers, requires the simultaneous targeting of multiple proteins and locating their respective expression in tissue samples. This information can be collected by imaging and registering adjacent sections from the same tissue sample and stained by immunohistochemistry (IHC). Registration accuracy should be on the scale of a few cells to enable protein colocalization to be assessed. METHODS: We propose a simple and efficient method based on the open-source elastix framework to register virtual slides of adjacent sections from the same tissue sample. We characterize registration accuracies for different types of tissue and IHC staining. RESULTS: Our results indicate that this technique is suitable for the evaluation of the colocalization of biomarkers on the scale of a few cells. We also show that using this technique in conjunction with a sequential IHC labeling and erasing technique offers improved registration accuracies. DISCUSSION: Brightfield IHC enables to address the problem of large series of tissue samples, which are usually required in clinical research. However, this approach, which is simple at the tissue processing level, requires challenging image analysis processes, such as accurate registration, to view and extract the protein colocalization information. CONCLUSIONS: The method proposed in this work enables accurate registration (on the scale of a few cells) of virtual slides of adjacent tissue sections on which the expression of different proteins is evidenced by standard IHC. Furthermore, combining our method with a sequential labeling and erasing technique enables cell-scale colocalization. PMID- 25125688 TI - Effects of computer-aided clinical decision support systems in improving antibiotic prescribing by primary care providers: a systematic review. AB - OBJECTIVE: To assess the effectiveness of computer-aided clinical decision support systems (CDSS) in improving antibiotic prescribing in primary care. METHODS: A literature search utilizing Medline (via PubMed) and Embase (via Embase) was conducted up to November 2013. Randomized controlled trials (RCTs) and cluster randomized trials (CRTs) that evaluated the effects of CDSS aiming at improving antibiotic prescribing practice in an ambulatory primary care setting were included for review. Two investigators independently extracted data about study design and quality, participant characteristics, interventions, and outcomes. RESULTS: Seven studies (4 CRTs, 3 RCTs) met our inclusion criteria. All studies were performed in the USA. Proportions of eligible patient visits that triggered CDSS use varied substantially between intervention arms of studies (range 2.8-62.8%). Five out of seven trials showed marginal to moderate statistically significant effects of CDSS in improving antibiotic prescribing behavior. CDSS that automatically provided decision support were more likely to improve prescribing practice in contrast to systems that had to be actively initiated by healthcare providers. CONCLUSIONS: CDSS show promising effectiveness in improving antibiotic prescribing behavior in primary care. Magnitude of effects compared to no intervention, appeared to be similar to other moderately effective single interventions directed at primary care providers. Additional research is warranted to determine CDSS characteristics crucial to triggering high adoption by providers as a perquisite of clinically relevant improvement of antibiotic prescribing. PMID- 25125689 TI - Cross-sectional comparison of coronary artery calcium scores between Caucasian men in the United States and Japanese men in Japan: the multi-ethnic study of atherosclerosis and the Shiga epidemiological study of subclinical atherosclerosis. AB - The incidence of coronary heart disease in the United States has declined, and prevalences of several coronary disease risk factors have become comparable to those in Japan. Therefore, the burden of coronary atherosclerosis may be closer among younger persons in the 2 countries. We aimed to compare prevalences of coronary atherosclerosis, measured with coronary artery calcium scores, between men in the 2 countries by age group (45-54, 55-64, or 65-74 years). We used community-based samples of Caucasian men in the United States (2000-2002; n = 1,067) and Japanese men in Japan (2006-2008; n = 832) aged 45-74 years, stratifying them into groups with 0, 1, 2, or >=3 of the following risk factors: current smoking, overweight, diabetes, dyslipidemia, and hypertension. We calculated adjusted odds ratios of US Caucasian men's having Agatston scores of >=10, >=100, and >=400 with reference to Japanese men. Overall, the odds of Caucasian men having each Agatston cutoff point were greater. The ethnic difference, however, became smaller in younger age groups. For example, adjusted odds ratios for Caucasian men's having an Agatston score of >=100 were 2.05, 2.43, and 3.86 among those aged 45-54, 55-64, and 65-74 years, respectively. Caucasian men in the United States had a higher burden of coronary atherosclerosis than Japanese men, but the ethnic difference was smaller in younger age groups. PMID- 25125690 TI - Validation of self-reported smokeless tobacco use by measurement of serum cotinine concentration among US adults. AB - Although investigators have assessed the relationship between self-reported cigarette smoking and biomarker levels, the validity of self-reported information on smokeless tobacco (SLT) use is uncertain. We used aggregated data from the 2003-2004, 2005-2006, 2007-2008, and 2009-2010 administrations of the National Health and Nutrition Examination Survey (NHANES) to compare self-reported SLT use with serum concentrations of cotinine, a metabolite of nicotine, among US adults aged >=18 years. Receiver operating characteristic analysis was used to determine the optimal serum cotinine cutpoint for discriminating SLT users from nonusers of tobacco, and concordance analysis was used to compare self-reported SLT use with cotinine levels. Among the 30,298 adult respondents who completed the NHANES during 2003-2010, 418 reported having exclusively used SLT and no other type of tobacco (cigarettes, cigars, or pipes) during the past 5 days, while 23,457 reported not using any tobacco. The optimal cotinine cutpoint for discriminating SLT users from non-tobacco users was 3.0 ng/mL (sensitivity=97.0%, specificity=93.0%), which was comparable to a revised cutpoint recommended for identifying adult cigarette smokers. Concordance with cotinine was 96.4% and 93.7% for self-reported SLT use and tobacco nonuse, respectively. These findings indicate that self-reported SLT use among adults correlates highly with serum cotinine levels and that the optimal cutpoint for minimizing misclassification of self-reported use is a serum cotinine concentration of 3.0 ng/mL. PMID- 25125692 TI - Stress ultrasound evaluation of medial elbow instability in a cadaveric model. AB - BACKGROUND: An injury of the ulnar collateral ligament (UCL) is potentially career threatening for elite overhead-throwing athletes. Stress ultrasonography (SUS) allows for a rapid, cost-effective, and noninvasive evaluation of the UCL and elbow joint both at rest and with applied stress. PURPOSE/HYPOTHESIS: To determine the amount of cadaveric elbow valgus gapping with sequential sectioning of medial elbow structures as measured by SUS. It was hypothesized that the greatest increase in ulnohumeral joint gapping would be noted with release of the anterior bundle of the UCL. STUDY DESIGN: Descriptive laboratory study. METHODS: Twelve cadaveric elbows were divided into 2 groups and dissected in reverse sequences under the direct supervision of an experienced orthopaedic surgeon. Baseline ultrasound and SUS with applied valgus loads were performed by an experienced radiologist. A valgus load was applied at each sectioning interval using a standardized device. Ulnohumeral joint gapping in millimeters was measured by SUS for each step as the width of the medial joint from the trochlea to the sublime tubercle. The mean increases in joint gapping (Delta) between each step were calculated to quantify the additional gapping achieved with release of each sequential stabilizer. RESULTS: Release of the anterior band of the anterior bundle resulted in a mean Delta of 2.0 mm (95% CI, 1.1-2.8 mm). Release of the posterior band of the anterior bundle resulted in a mean Delta of 1.4 mm (95% CI, 0.6-2.2 mm). Release of the entire anterior bundle caused a mean increase in ulnohumeral valgus joint gapping of 3.4 mm (95% CI, 2.4-4.3 mm). Release of the remaining individual structures each resulted in a mean increase in valgus joint gapping of <=0.8 mm. CONCLUSION: The results of the current cadaveric study suggest that different amounts of gapping are seen on SUS with sectioning of the medial elbow stabilizers. The hypothesis was confirmed with release of the anterior bundle of the UCL resulting in the greatest increase in joint gapping as measured by SUS. CLINICAL RELEVANCE: This study illustrates that SUS can identify the contributions of each anatomic portion of the UCL and the flexor-pronator mass to ulnohumeral joint stability in a cadaveric model. PMID- 25125693 TI - Cost-effectiveness analyses in orthopaedic sports medicine: a systematic review. AB - BACKGROUND: As increasing attention is paid to the cost of health care delivered in the United States (US), cost-effectiveness analyses (CEAs) are gaining in popularity. Reviews of the CEA literature have been performed in other areas of medicine, including some subspecialties within orthopaedics. Demonstrating the value of medical procedures is of utmost importance, yet very little is known about the overall quality and findings of CEAs in sports medicine. PURPOSE: To identify and summarize CEA studies in orthopaedic sports medicine and to grade the quality of the available literature. STUDY DESIGN: Systematic review. METHODS: A systematic review of the literature was performed to compile findings and grade the methodological quality of US-based CEA studies in sports medicine. The Quality of Health Economic Studies (QHES) instrument and the checklist by the US Panel on Cost-effectiveness in Health and Medicine were used to assess study quality. One-sided Fisher exact testing was performed to analyze the predictors of high-quality CEAs. RESULTS: Twelve studies met inclusion criteria. Five studies examined anterior cruciate ligament reconstruction, 3 studies examined rotator cuff repair, 2 examined autologous chondrocyte implantation, 1 study examined hip arthroscopic surgery, and 1 study examined the operative management of shoulder dislocations. Based on study findings, operative intervention in sports medicine is highly cost-effective. The quality of published evidence is good, with a mean quality score of 81.8 (range, 70-94). There is a trend toward higher quality in more recent publications. No significant predictor of high quality evidence was found. CONCLUSION: The CEA literature in sports medicine is good; however, there is a paucity of studies, and the available evidence is focused on a few procedures. More work needs to be conducted to quantify the cost effectiveness of different techniques and procedures within sports medicine. The QHES tool may be useful for the evaluation of future CEAs. PMID- 25125694 TI - Drug selection and dosing in pregnant cancer patients: insights from clinical pharmacokinetics. PMID- 25125691 TI - Marginal structural models in occupational epidemiology: application in a study of ischemic heart disease incidence and PM2.5 in the US aluminum industry. AB - Marginal structural models (MSMs) and inverse probability weighting can be used to estimate risk in a cohort of active workers if there is a time-varying confounder (e.g., health status) affected by prior exposure-a feature of the healthy worker survivor effect. We applied Cox MSMs in a study of incident ischemic heart disease and exposure to particulate matter with aerodynamic diameter of 2.5 MUm or less (PM2.5) in a cohort of 12,949 actively employed aluminum workers in the United States. The cohort was stratified by work process into workers in smelting facilities, herein referred to as "smelters" and workers in fabrication facilities, herein referred to as "fabricators." The outcome was assessed by using medical claims data from 1998 to 2012. A composite risk score based on insurance claims was treated as a time-varying measure of health status. Binary PM2.5 exposure was defined by the 10th-percentile cutoff for each work process. Health status was associated with past exposure and predicted the outcome and subsequent exposure in smelters but not in fabricators. In smelters, the Cox MSM hazard ratio comparing those always exposed above the cutoff with those always exposed below the cutoff was 1.98 (95% confidence interval: 1.18, 3.32). In fabricators, the hazard ratio from a traditional Cox model was 1.34 (95% confidence interval: 0.98, 1.83). Results suggest that occupational PM2.5 exposure increases the risk of incident ischemic heart disease in workers in both aluminum smelting and fabrication facilities. PMID- 25125696 TI - Evaluation of blood perfusion by laser speckle contrast analysis in different areas of hands and face in patients with systemic sclerosis. PMID- 25125697 TI - Phytic acid in green leaves of herbaceous plants-temporal variation in situ and response to different nitrogen/phosphorus fertilizing regimes. AB - Phytic acid is the major storage compound for phosphorus (P) in plants. While accounting for up to 90 % in many seeds, usually only <10 % of total P is found in phytic acid in green leaves. This study follows up on the findings of a recent review of the occurrence of phytic acid in green leaves which revealed that (i) the current knowledge of phytic acid in leaves is mostly based on data from (fertilized) crop plants and (ii) the proportion of total P in phytic acid seems to decrease with improved P status in leaves in contrast to an increase in seeds and fruit. We studied five species of wild herbaceous plants in the field and under controlled conditions. Foliar P concentrations were much lower than those of the crops of earlier studies, but the proportion of P in phytic acid was similar, with little variation during the observation period. Both the field data and the experimental data showed a statistically indistinguishable negative correlation of phytic acid-P/total P and total P. In contrast to our expectation, this negative relationship was not related to differences in relative growth rates. We conclude that (i) our data of phytic acid concentrations in leaves of wild plants are in line with earlier observations on crops, and (ii) the trend towards lower proportions of phytic acid-P with increasing P status is probably a general phenomenon. Currently lacking a convincing explanation for the second observation, the role of phytic acid in foliar P metabolism is still unclear. PMID- 25125695 TI - FHL2 regulates the resolution of tissue damage in chronic inflammatory arthritis. AB - OBJECTIVE: We analysed the role of the adaptor molecule four-and-a-half Lin11, Isl-1 & Mec-3 (LIM) domain protein 2 (FHL2) in the activation of fibroblast-like synoviocytes in human rheumatoid arthritis (RA) and tumour necrosis factor alpha (TNFalpha)-dependent animal models of the disease. METHODS: Synovial tissues of patients with RA and osteoarthritis (OA) as well as hind paw sections from arthritic human TNFalpha transgenic (hTNFtg) mice and synovial fibroblasts from these were analysed. The effects of cytokines on the expression of FHL2 and disease-relevant matrixmetalloproteases (MMPs) were determined. Analyses of human tissue specimens from patients treated with anti-TNFalpha as well as anti TNFalpha treatment of hTNFtg mice were performed to substantiate the TNFalpha effects on FHL2 levels. FHL2(-/-) mice and hTNFtg mice (with constitutive or inducible transgene expression) were crossbred to generate TNFalpha overexpressing FHL2-deficient animals. Signalling pathways were analysed in cells from these mice and in human cells after knock down of FHL2 by western blot. RESULTS: FHL2 levels were higher in RA than in OA and in hTNFtg than in wild-type mice. Surprisingly, while transforming growth factor (TGF)beta-induced FHL2 expression, TNFalpha suppressed FHL2. In vivo, anti-TNFalpha treatment led to higher FHL2 levels both in RA patients and hTNFtg mice. The loss of FHL2 increased joint destruction in hTNFtg mice, which was accompanied by elevated MMP 13. In vitro, TNFalpha-mediated MMP-13 was significantly higher in FHL2(-/-) cells and after knock down of FHL2, which was caused by prolonged p38 MAPK activation. CONCLUSIONS: These data suggest that FHL2 serves as a protective factor and that, rather than promoting the pathology, the upregulation of FHL2 in RA occurs in frame of a regenerative attempt. PMID- 25125699 TI - Adult Child Migration and the Health of Elderly Parents Left Behind in Mexico. PMID- 25125698 TI - Manipulating the antioxidant capacity of halophytes to increase their cultural and economic value through saline cultivation. AB - Halophytes, salt-tolerant plants, are a source of valuable secondary metabolites with potential economic value. The steady-state pools of many stress-related metabolites are already enhanced in halophytes when compared with glycophytes, but growth under conditions away from the optimum can induce stress and consequently result in changes to secondary metabolites such as antioxidants. However, direct evidence for increasing the concentration of valuable secondary metabolites as a consequence of altering the salinity of the growing environment still remains equivocal. To address this, we analysed a range of metabolites with antioxidant capacity (including total phenols, flavonoids, ascorbate, reduced/oxidized glutathione and reactive oxygen species scavenging enzymes) in seedlings and plants from different families (Amaranthaceae, Brassicaceae, Plantaginaceae and Rhizophoraceae) and habitats grown under different salt concentrations. We show that it is possible to manipulate the antioxidant capacity of plants and seedlings by altering the saline growing environment, the length of time under saline cultivation and the developmental stage. Among the species studied, the halophytes Tripolium pannonicum, Plantago coronopus, Lepidium latifolium and Salicornia europaea demonstrated the most potential as functional foods or nutraceuticals. PMID- 25125700 TI - What Goes Up Must Come Down? Experimental Evidence on Intuitive Forecasting. AB - Do laboratory subjects correctly perceive the dynamics of a mean-reverting time series? In our experiment, subjects receive historical data and make forecasts at different horizons. The time series process that we use features short-run momentum and long-run partial mean reversion. Half of the subjects see a version of this process in which the momentum and partial mean reversion unfold over 10 periods ('fast'), while the other subjects see a version with dynamics that unfold over 50 periods ('slow'). Typical subjects recognize most of the mean reversion of the fast process and none of the mean reversion of the slow process. PMID- 25125701 TI - Electrical interactions in the cell: Asymmetric screening in a watery antiverse. AB - The problem of electrostatics in biomolecular systems presents an excellent opportunity for cross-disciplinary science and a context in which fundamental physics is called for to answer complex questions. Due to the large density in biological cells of charged biomacromolecules such as protein factors and DNA, it is challenging to understand quantitatively the electric forces in these systems. Two questions are especially puzzling. First, how is it that such a dense system of charged molecules does not simply aggregate in random and non-functional ways? Second, since some mechanism apparently prevents such aggregation, how is it that binding of biomolecules still occurs so reliably? Recognizing the role of water as a universal solvent in living systems is key to understanding these questions. We present a simplified physical model in which water is regarded as a medium of high dielectric constant that nevertheless exhibits the key features essential for answering the two questions presented. The answer to the first question lies in the strong screening ability of water, which reduces the energy scale of the electrostatic interactions. Furthermore, our model reveals the existence of asymmetric screening, a pronounced asymmetry between the screening for a system with like charges and that for a system with opposite charges, and this provides an answer to the second question. PMID- 25125702 TI - An AFM Study of the Effects of Silanization Temperature, Hydration, and Annealing on the Nucleation and Aggregation of Condensed OTS Domains on Mica. AB - Partial monolayers of octadecyltrichlorosilane (OTS) were formed on mica under different reaction conditions in which the silanization temperature, time, and amount of water adsorbed on the mica substrates were varied. OTS surface coverage increased with silanization time for all samples; however, the amount and distribution of adsorbed OTS varied greatly under these different reaction conditions. AFM analysis showed that OTS formed two phases on mica silanized at 25 degrees C: condensed "island-like" domains and expanded "liquid-like" domains. Partially dehydrated mica silanized at 9 degrees C, however, displayed only condensed domains which were of smaller size compared to those on the 25 degrees C samples. The lateral diffusion and aggregation of small condensed OTS domains to form larger aggregates was evident on all surfaces except the 25 degrees C partially dehydrated mica. A uniform distribution of many small condensed domains surrounded by expanded OTS phases was seen instead. Extended annealing resulted in surface diffusion and aggregation of these domains and nucleation of new condensed domains from the surrounding expanded OTS phases. These observations are consistent with a deposition, diffusion, and aggregation model (DDA) which allows for activated diffusion; however, rigorous modeling is not presented here. PMID- 25125703 TI - Parents' Relationship Quality and Children's Behavior in Stable Married and Cohabiting Families. AB - Although an extensive literature has shown that family structure is linked with child well-being, less well understood is how the dynamics within families affect children, in particular the extent to which positive mother-father relationship quality is linked with children's outcomes. In this study the authors used data from the Fragile Families and Child Wellbeing Study (N = 773) to examine how couple supportiveness in stable coresident families is related to children's externalizing and internalizing behavioral problems over ages 3 through 9. Using latent growth curve and fixed effects models, they found that parents' greater supportiveness has a slight association with lower levels of children's behavioral problems. Using cross-lagged structural equation models to examine the direction of the association, they also found some evidence that parents' relationship quality and children's behavioral problems are reciprocally related. Overall, this study suggests that more positive couple interactions are beneficial for children residing with both of their biological parents. PMID- 25125704 TI - Single Motherhood, Living Arrangements, and Time With Children in Japan. AB - The authors examined relationships between single parenthood and mothers' time with children in Japan. Using data from the 2011 National Survey of Households with Children (N = 1,926), they first demonstrate that time spent with children and the frequency of shared dinners are significantly lower for single mothers than for their married counterparts. For single mothers living alone, less time with children reflects long work hours and work-related stress. Single mothers coresiding with parents spend less time with children and eat dinner together less frequently than either married mothers or their unmarried counterparts not living with parents, net of (grand)parental support, work hours, income, and stress. The findings suggest that rising divorce rates and associated growth in single-mother families may have a detrimental impact on parents' time with children in Japan and that the relatively high prevalence of intergenerational coresidence among single mothers may do little to temper this impact. PMID- 25125705 TI - Predictors of Self-reported Sexually Transmitted Diseases among Homeless and Runaway Adolescents. AB - Path analysis was used to investigate factors associated with self-reported sexually transmitted diseases among 569 homeless and runaway adolescents in four Midwestern states. Youth were interviewed by outreach workers directly on the streets, in shelters, and in drop-in centers. Results indicated that family abuse was positively related to substance use, affiliation with friends who sold sex, and time on own. Early family abuse indirectly increased the likelihood of self reported sexually transmitted diseases through time on own, substance use, friends selling sex, and risky sexual behaviors. Finally, substance use and affiliation with friends who sold sex was positively associated with risky sexual behaviors, which in turn was related to self-reported sexually transmitted diseases. No significant gender interactions were found for this model. PMID- 25125706 TI - Weighted Area Under the Receiver Operating Characteristic Curve and Its Application to Gene Selection. AB - Partial area under the ROC curve (PAUC) has been proposed for gene selection in Pepe et al. (2003) and thereafter applied in real data analysis. It was noticed from empirical studies that this measure has several key weaknesses, such as an inability to reflect nonuniform weighting of different decision thresholds, resulting in large numbers of ties. We propose the weighted area under the ROC curve (WAUC) in this paper to address the problems associated with PAUC. Our proposed measure enjoys a greater flexibility to describe the discrimination accuracy of genes. Nonparametric and parametric estimation methods are introduced, including PAUC as a special case, along with theoretical properties of the estimators. We also provide a simple variance formula, yielding a novel variance estimator for nonparametric estimation of PAUC, which has proven challenging in previous work. The proposed methods permit sensitivity analyses, whereby the impact of differing weight functions on gene rankings may be assessed and results may be synthesized across weights. Simulations and re-analysis of two well-known microarray datasets illustrate the practical utility of WAUC. PMID- 25125707 TI - Children in Institutional Care: Delayed Development and Resilience. AB - Children exposed to institutional care often suffer from "structural neglect" which may include minimum physical resources, unfavorable and unstable staffing patterns, and social-emotionally inadequate caregiver-child interactions. This chapter is devoted to the analysis of the ill effects of early institutional experiences on resident children's development. Delays in the important areas of physical, hormonal, cognitive, and emotional development are discussed. The evidence for and against the existence of a distinctive set of co-occurring developmental problems in institutionalized children is weighed and found to not yet convincingly demonstrate a "post-institutional syndrome". Finally, shared and non-shared features of the institutional environment and specific genetic, temperamental, and physical characteristics of the individual child are examined that might make a crucial difference in whether early institutional rearing leaves irreversible scars. PMID- 25125708 TI - Sensitive Periods. AB - This chapter reviews sensitive periods in human brain development based on the literature on children raised in institutions. Sensitive experiences occur when experiences are uniquely influential for the development of neural circuitry. Because in humans, we make inferences about sensitive periods from evaluations of complex behaviors, we underestimate the occurrence of sensitive periods at the level of neural circuitry. Although we are most interested in complex behaviors, such as IQ or attachment or externalizing problems, many different sensitive periods at the level of circuits probably underlie these complex behaviors. Results from a number of studies suggest that across most, but not all, domains of development, institutional rearing limited to the first 4-6 months of life is associated with no significant increase risk for long-term adverse effects relative to non-institutionalized children. Beyond that, evidence for sensitive periods is less compelling, meaning that "the earlier the better" rule for enhanced caregiving is a reasonable conclusion at the current state of the science. PMID- 25125709 TI - Tetrasubstituted pyrazinones derived from the reaction of praziquantel with N bromosuccinimide. AB - When praziquantel was exposed to N-bromosuccinimide in the presence of ethanol, a tricyclic 3-bromo-1-ethoxy pyrazinone was formed. From this and the analogous 1,3 dibromopyrazinone, a small library of 3-alkylamino-1-ethoxy, 1,3-dialkoxy, 3 alkoxy-1-bromo, and 3-alkylamino-1-bromo substituted pyrazinones were synthesized in high yields. PMID- 25125710 TI - Enantioselective synthesis of decalin structures with all-carbon quaternary centers via one-pot sequential Cope/Rauhut-Currier reaction. AB - The first example of one-pot sequential Cope/Rauhut-Currier reactions are reported and used to make functionalized decalin structures with all-carbon quaternary stereocenters. The substrates for the new sequential reaction are generated through a six-step sequence including an enantioselective Birch reduction-allylation reaction which makes the overall process asymmetric. PMID- 25125711 TI - Varying coefficient subdistribution regression for left-truncated semi-competing risks data. AB - Semi-competing risks data frequently arise in biomedical studies when time to a disease landmark event is subject to dependent censoring by death, the observation of which however is not precluded by the occurrence of the landmark event. In observational studies, the analysis of such data can be further complicated by left truncation. In this work, we study a varying co-efficient subdistribution regression model for left-truncated semi-competing risks data. Our method appropriately accounts for the specifical truncation and censoring features of the data, and moreover has the flexibility to accommodate potentially varying covariate effects. The proposed method can be easily implemented and the resulting estimators are shown to have nice asymptotic properties. We also present inference, such as Kolmogorov-Smirnov type and Cramer Von-Mises type hypothesis testing procedures for the covariate effects. Simulation studies and an application to the Denmark diabetes registry demonstrate good finite-sample performance and practical utility of the proposed method. PMID- 25125712 TI - Nativity Differences in Youths' Weight Trajectories: Foreign-Born Health Integration during the Transition to Adulthood. AB - Nativity differences in youths' health in the United States are striking, with the children of foreign-born parents showing more favorable outcomes than those of native-born parents. Very little is known about how inequalities evolve within the same individuals over time, or more generally about life cycle aspects of the health integration of youth with migration backgrounds. Using data from the National Longitudinal Study of Adolescent Health, I examine nativity differences in trajectories of weight gain during adolescence and early adulthood, as well as the degree to which trajectories are stratified by race/ethnicity and socioeconomic status. Do nativity differences converge, diverge or remain stable over time, and how are patterns socially stratified within and across nativity groups? I find that first-generation adolescents begin at a lower weight than their third generation peers and gain weight at a significantly slower pace, producing meaningful differences by early adulthood. More complex examination of the relationship between nativity and weight gain reveals additional differences by ethnicity: the foreign-born advantage over time does not extend as strongly to Hispanic adolescents. The findings demonstrate how the health-related integration of foreign-born youth is tied to race/ethnicity and socioeconomic circumstances, and suggest the need to examine the ways in which social circumstances and health change together. PMID- 25125713 TI - Neighborhood Characteristics, Parental Practices and Children's Math Achievement in Elementary School. AB - : This paper investigates the relationships among neighborhood characteristics, education-related parental practices, and children's academic achievement during a critical but under-studied stage of children's educational trajectories - the elementary school years. Using a large, nationally representative database of American elementary school students - the Early Childhood Longitudinal Study - Kindergarten Cohort (ECLS-K) - and contextual data from the 2000 U.S. Census, we examine parental practices and neighborhood characteristics at the beginning of children's school careers (grades K-1) and their associations with math achievement through the end of the 5th grade. FINDINGS: Net of family-level characteristics, higher levels of early education- oriented parental practices were associated with higher mathematics achievement at the end of 5th grade, while neighborhood disadvantage was associated with lower 5th grade math achievement. Families residing in high poverty, high unemployment, low-education neighborhoods employed fewer education- oriented practices with their kindergarten- first grade children, but the positive effect of such parental practices on children's mathematics achievement was stronger for children who live in disadvantaged neighborhoods. PMID- 25125714 TI - President's address: Mary Shelley, Frankenstein, and the dark side of medical science. PMID- 25125715 TI - A novel T cell evasion mechanism in persistent RNA virus infection. AB - Hepatitis C virus (HCV) and GB virus type C (GBV-C) are associated with impaired T cell function despite the fact that HCV replicates in hepatocytes and GBV-C in a small proportion of lymphocytes. Recently, we showed that HCV and GBV-C E2 envelope proteins reduce T cell activation via the T cell receptor (TCR) by competing for phosphorylation with a critical kinase in the TCR signaling cascade (Lck). E2 interfered with TCR signaling in E2 expressing cells and in bystander cells. The bystander effect was mediated by virus particles and extracellular microvesicular particles (exosomes). Multiple kinase substrate sites are predicted to reside on viral structural proteins and based on bioinformatic predictions, many RNA virus pathogens may interfere with TCR signaling via a similar mechanism. Identification of T cell inhibitory effects of virus structural proteins may provide novel approaches to enhance the immunogenicity and memory of viral vaccines. PMID- 25125717 TI - Scanning the chronic disease terrain: prospects and opportunities. AB - The disease burden in the United States has changed radically in the past 100 years. A striking decrease in infectious diseases as causes of morbidity and mortality has been followed by a steady increase in morbidity and mortality rates from chronic disease, which is now the dominant health issue facing the country, at levels justifying considering chronic disease as having reached epidemic proportions. Research in recent years has shown that many of the common chronic diseases are malleable, i.e., susceptible to therapeutic or preventive efforts aimed at risk factors and susceptible age eras and populations. Although clinical and population-oriented interventions have been increasingly successful in recent decades, more intensive and coordinated preventive efforts will be required, including effective partnerships between clinical medicine and other sectors, particularly at-risk individuals, government, and public health. Robust joint efforts are not only needed, but are likely to be successful. PMID- 25125716 TI - Translational studies in older men using testosterone to treat sarcopenia. AB - Sarcopenia is the loss of skeletal muscle mass and strength that occurs with aging. Our research group has found an efficacious administration paradigm using testosterone to combat sarcopenia in humans. In addition, our research has uncovered an important regulatory enzyme of inflammation, nuclear factor-kappaB inducing kinase that may regulate human skeletal muscle catabolism, and that appears to be counter-regulated by administration of standard doses of testosterone. This is important because a number of age-related clinical circumstances trigger acute and chronic muscle loss including cancer, chronic obstructive pulmonary disease, hospitalization, acute and chronic illness, and diseases in which systemic inflammation occurs. Moreover, it is often the treatment itself that can induce muscle loss. For example, glucocorticoids are tremendously effective at reducing inflammation and are a frontline therapy for many inflammatory-based diseases, yet paradoxically trigger muscle loss. We will discuss our research findings and the clinical significance of our human clinical translational research with testosterone. PMID- 25125718 TI - "Reverse genomics" and human endogenous retroviruses. AB - Over millions of years, actively replicating retroviruses entered the human genome and through time became a stable and substantial part of the inherited genetic material. A remarkable 8% of the human genome is accounted for by endogenous retroviruses, whose biological importance has not yet been elucidated. In studying the RNA of these endogenous retroviruses in the blood of living human subjects with HIV infection, we have discovered a whole new family of these viruses that had been hidden in the centromeres of specific human chromosomes. These retroviruses have specific sequences that can elucidate their chromosome of origin. As centromeres represent the most substantial remaining frontier of human genomics, these viral sequences can provide a "bar-code" that can be used to study the role of centromeres in biology and in disease. This work also highlights the efficacy of using "reverse genomics" to understand and annotate the human genome. PMID- 25125720 TI - The natural history of acute dilated cardiomyopathy. AB - INTRODUCTION: Acute dilated cardiomyopathy (ADCM) is a frequent cause for referral for cardiac transplantation yet its prognosis and natural history on contemporary therapy remain uncertain. METHODS: The Multicenter Intervention in Myocarditis and Acute Cardiomyopathy (IMAC)-2 trial enrolled 373 patients at 12 academic medical centers with left ventricular ejection fraction (LVEF) <= 40%, heart failure symptoms < 6 months duration, and a diagnostic evaluation consistent with idiopathic cardiomyopathy or acute myocarditis. The natural history of ADCM in an earlier era (1975-2000) was also examined via a MEDLINE search of published observational studies. RESULTS: Mean age of the IMAC-2 study cohort was 45 +/- 4 years and 38% were female. Mean initial LVEF was 24% +/- 8% and increased to 40% +/- 12% during treatment with ACE-I/ARB (82%), and a beta blocker (94%). Transplantation-free survival at 1, 2, and 4 years was 94%, 92%, and 86%, respectively. This survival rate was substantially higher than the prior era. Multivariate predictors of improvement in LVEF were smaller LV dimension and higher systolic blood pressure whereas black race and higher initial New York Heart Association functional class were associated with lower final LVEF. Genotypic variation did not correlate with response to pharmacological therapy. CONCLUSION: Earlier diagnosis and aggressive pharmacologic and device-based therapy of ADCM has led to improved prognosis. PMID- 25125719 TI - Bitter taste receptors in the wrong place: novel airway smooth muscle targets for treating asthma. AB - There is a need to expand the classes of drugs used to treat obstructive lung diseases to achieve better outcomes. With only one class of direct bronchodilators (beta-agonists), we sought to find receptors on human airway smooth muscle (ASM) that act via a unique mechanism to relax the muscle, have a diverse agonist binding profile to enhance the probability of finding new therapeutics, and relax ASM with equal or greater efficacy than beta-agonists. We have found that human and mouse ASM express six bitter taste receptor (TAS2R) subtypes, previously thought only to exist in taste buds of the tongue. Agonists acting at TAS2Rs evoke profound bronchodilation via a Ca(2+)-dependent mechanism. TAS2R function is not altered in asthma models, undergoes minimal tachyphylaxis upon repetitive dosing, and relaxes even under extreme desensitization of relaxation by beta-agonists. Taken together, TAS2Rs on ASM represent a novel pathway to consider for development of agonists in the treatment of asthma and chronic obstructive lung disease. PMID- 25125721 TI - Teaching evidence-based medicine in the former Soviet Union: lessons learned. AB - Between 2009 and 2012, I taught principles of evidence-based medicine and clinical research in Russia, Tatarstan, Moldova, and Kazakhstan. The Soviet Union left a medical legacy characterized by balkanization of top tier medicine in highly specialized centers, so there was little capability for multidiscipinary care. In addition, the authoritarian government led to a persistently top-down tradition of medical education and practice, which one of my Russian colleagues aptly named "eminence-based medicine." After the fall of the Soviet Union, funding for science and medical research was drastically cut, leading to a struggle for resources and politicization of resource decisions. At present, prejudices and beliefs about disease and treatment persist untested, limited English language competency impedes acquisition of new knowledge, and restriction of resources cripples innovation. Yet none of these conditions are unknown to us in the United States. Physicians may resist evidence that challenges long-held beliefs, and patients want us to make decisions based on their individual case, not evidence arising from studying other people. As physicians, we need to understand how to communicate with and frame our arguments so that they can be understood and received favorably. Can we draw lessons from trying to teach evidence-based medicine in the former Soviet Union? PMID- 25125724 TI - Gordon Wilson lecture: opening doors worldwide through medical science: personal reflections. PMID- 25125725 TI - Curing genetic disease with gene therapy. AB - Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile. PMID- 25125726 TI - The immune system in hypertension. AB - Hypertension is generally attributed to perturbations of the vasculature, the kidney, and the central nervous system. During the past several years, it has become apparent that cells of the innate and adaptive immune system also contribute to this disease. Macrophages and T cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension, and likely contribute to end-organ damage. We have shown that mice lacking lymphocytes, such as recombinase-activating gene-deficient (RAG-1(-/-)) mice, have blunted hypertension in response to angiotensin II, increased salt levels, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Others have shown that mice with severe combined immunodeficiency have blunted hypertension in response to angiotensin II. Deletion of the RAG gene in Dahl salt-sensitive rats reduces the hypertensive response to salt feeding. The central nervous system seems to orchestrate immune cell activation. We produced lesions of the anteroventral third ventricle and showed that these block T cell activation in response to angiotensin II. Likewise, we showed that genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and T cell activation. Current evidence indicates that production of cytokines including tumor necrosis factor alpha, interleukin 17, and interleukin 6 contribute to hypertension, likely by promoting vasoconstriction, production of reactive oxygen species, and sodium reabsorption in the kidney. We propose a working hypothesis linking the sympathetic nervous system, immune cells, the production of cytokines, and ultimately vascular and renal dysfunction, leading to augmentation of hypertension. PMID- 25125727 TI - Impact of denervated myocardium on improving risk stratification for sudden cardiac death. AB - Between 184,000 and 462,000 Americans die suddenly each year. Fifty percent to 70% of these deaths are due to ventricular tachycardia/fibrillation (VT/VF). We tested whether hibernating myocardium or myocardial sympathetic denervation identifies patients at high-risk for developing VT/VF independently of ejection fraction (EF). Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion ((13)N-ammonia), and viability (insulin-stimulated (18)F-2-deoxyglucose [(18)FDG]) in patients with ischemic cardiomyopathy (EF < 35%) eligible for a primary prevention implantable cardioverter defibrillator (ICD). The primary end point was sudden cardiac arrest (SCA) defined as arrhythmic death or ICD discharge for VT/VF > 240 bpm. Volumes of total denervated (P = .001) and viable denervated myocardium ((11)C-HED-(18)FDG mismatch, P = .03) predicted SCA, whereas hibernating and infarcted myocardium did not. Multivariate analysis identified four independent predictors of SCA: denervated myocardium > 37.6% of left ventricule (LV), LV end-diastolic volume > 98 mL/m(2), creatinine level > 1.49 mg/dL, and no angiotensin- inhibition therapy. Denervated myocardium had a hazard ratio of 3.5 for SCA (10.3%/year vs. 3.0%/year, p=0.001). Absence of all four factors predicted low risk (44% of cohort; SCA <1%/y) whereas two or more factors identified subjects at high-risk (20% of cohort; SCA 12%/y). Denervated myocardium quantified using PET strongly predicts risk of SCA, and is independent of EF, infarct volume, and other clinical variables. PMID- 25125728 TI - Back to the beginning for the Eighth Evacuation Hospital in Morocco during World War II 70 years ago. PMID- 25125731 TI - Three ways to die suddenly: do they all require calcium calmodulin-dependent protein kinase II? AB - Sudden cardiac death occurs due to a limited number of pathological events. The heart can beat too fast or too slow to maintain adequate cardiac output or the heart can rupture. Here we survey recent evidence that excessive activation of calcium calmodulin-dependent protein kinase II by three core neurohumoral pathways or by oxidant stress can lead to sudden cardiac death due to sinus node dysfunction and bradycardia, ventricular tachycardia or fibrillation, and cardiac rupture. PMID- 25125734 TI - The endemic mimic: blastomycosis an illness often misdiagnosed. AB - One of the endemic fungi, Blastomyces dermatitidis, can cause epidemics of infection with multiple persons involved in a point source outbreak but more commonly causes sporadic cases of infection within the areas of endemicity. Blastomycosis can present as an acute pneumonia which is often misdiagnosed as acute pneumococcal pneumonia or the infection may present as a chronic pneumonia along with weight loss, night sweats, hemoptysis, and a lung mass suggesting tuberculosis or carcinoma of the lung. Extrapulmonary infection with B. dermatitidis is protean with many different manifestations. Most commonly, skin or subcutaneous lesions are found with either a verrucous or warty appearance or in an ulcerative form. Cases have been misidentified as keratoacanthoma, pyoderma gangrenosum, carcinoma, or as Weber-Christian panniculitis if there are nodular subcutaneous lesions. Essentially any site or organ can have lesions of disseminated blastomycosis. In our series, cases of laryngeal carcinoma, adrenal insufficiency, thyroid nodules, granulomatous hypercalcemia, abnormal mammograms thought to represent breast carcinoma, otitis media with cranial extension, immune thrombocytopenic purpura, and hemolytic anemia of unknown cause have been misdiagnosed and blastomycosis subsequently identified as the cause. This infection causes manifestations which mimic many other more commonly diagnosed conditions and must always be considered by clinicians practicing in the endemic region. PMID- 25125735 TI - The role of pragmatic clinical trials in the evolution of learning health systems. AB - Pragmatic clinical trials (PCTs) test clinical interventions (eg, treatments, diagnostic tests, delivery strategies) that are widely used in practice and for which there is often clinical equipoise. Similar to traditional explanatory trials of novel therapeutics, PCTs use randomization to decrease selection bias. In contrast, PCTs rely on extant data sources (eg, electronic medical records [EMRs]) and test interventions that can be implemented with minimal research infrastructures. Thus, PCTs have drawn interest as vehicles for decreasing the cost of clinical research and for creating learning health systems, which, as articulated by the Institute of Medicine, seek to generate new knowledge as an integral by-product of the delivery experience. However, realizing this vision for PCTs will require innovative approaches for engaging clinicians, improving the efficiency of subject recruitment, improving the reliability of EMR data, and new paradigms for the regulatory review of low-risk trials to decrease unncessary hurdles to practice-based knowledge generation. PMID- 25125736 TI - Quantitative human phenotyping: the next frontier in medicine. PMID- 25125741 TI - The Bert and Peggy Dupont lecture: prelude to war, a gentlemen's affair: the story behind the Battle of Fort Sumter, April 1861. PMID- 25125737 TI - Addressing the global burden of chronic kidney disease through clinical and translational research. AB - Worldwide, an estimated 200 million people have chronic kidney disease (CKD). In the United States, African Americans (AAs) have a four-fold excess risk of CKD compared to non-Hispanic white people and globally, people in the low-to-middle income countries of Asia and Sub-Saharan Africa have the highest rates of CKD. Annually, more than 500,000 individuals develop end-stage renal disease (or CKD stage 5) in Sub-Saharan Africa alone and the vast majority of these patients suffer premature mortality. The health care costs and economic burden of CKD are huge and not sustainable even in advanced Western countries. A recent discovery on the role of Apolipoprotein 1 (APOL1) G1 and G2 renal risk variants in AAs has a huge potential to unravel the etiology of CKD in both AA and other black populations. Under the National Institutes of Health (NIH)-sponsored Human Heredity and Health in Africa (H3Africa) initiative, a large prospective genetic study of CKD is being conducted in 8000 participants in four African countries (Ethiopia, Ghana, Kenya, and Nigeria; for a total population of 320 million). This and other basic research studies in the United States could potentially shed great insight into the genetics and biologic mechanisms involved in the excess predilection of Africans and AAs to CKD. PMID- 25125744 TI - The Jeremiah Metzger lecture: new additions to the toolbox for global malaria eradication. PMID- 25125745 TI - Mechanisms of hypoglycemia and exercise-associated autonomic dysfunction. AB - It is well established that diabetes can lead to multiple microvascular and macrovascular complications. Several large scale randomized multicenter studies have shown that intensifying glucose control decreases microvascular and, to a certain extent, macrovascular complications of diabetes. However, intensifying glucose control in both type 1 and type 2 diabetes increases the risk of developing hypoglycemia, one of the most feared complications of people with the disease. The mechanisms responsible for intensive therapy causing increased hypoglycemia in patients with diabetes have been extensively investigated. It is now known that a single episode of hypoglycemia can blunt the body's normal counterregulatory defenses against subsequent hypoglycemia or exercise. Similarly, a single bout of exercise can also blunt counterregulatory responses against subsequent hypoglycemia. Both neuroendocrine and autonomic nervous system responses are reduced by prior hypoglycemia and/or exercise. Work from several laboratories has identified multiple physiologic mechanisms involved in the pathogenesis of this hypoglycemia and exercise-associated counterregulatory failure. By continuing to study these mechanisms, some promising approaches to amplify counterregulatory responses to hypoglycemia are being discovered. PMID- 25125746 TI - Kidney injury molecule-1: a translational journey. AB - Kidney injury molecule-1 (KIM-1, also named TIM-1 and HAVCR-1) was identified as the most highly upregulated protein in the proximal tubule of the kidney after injury. This protein is present with injury in multiple species including man, and also after a large number of acute and chronic insults to the kidney. It is a type-1 membrane protein whose ectodomain is released into the lumen of the tubule. The ectodomain is heavily glycosylated and stable and appears in the urine after injury. It has been qualified by the United States Food and Drug Administration and the European Medicines Agency for preclinical assessment of nephrotoxicity and on a case-by-case basis for clinical evaluation. As a biomarker in humans, its utility has been demonstrated in acute and chronic injury and in renal cell carcinoma, a condition similar to injury, where there is dedifferentiation of the epithelial cell. KIM-1 is a phosphatidylserine receptor which recognizes apoptotic cells directing them to lysosomes. It also serves as a receptor for oxidized lipoproteins and hence is important for uptake of components of the tubular lumen which may be immunomodulatory and/or toxic to the cell. KIM-1 is unique in being the first molecule, not also present on myeloid cells, that transforms kidney proximal epithelial cells into semi-professional phagocytes. Data suggest that KIM-1 expression is protective during early injury, whereas in chronic disease states, prolonged KIM-1 expression may be maladaptive and may represent a target for therapy of chronic kidney disease. PMID- 25125748 TI - "An aristocracy of talent": the South Carolina physician-naturalists and their times. AB - During the natural history movement of the 18th and early 19th centuries, Charleston as a center was rivaled in the United States only by Philadelphia, New York, and Boston. Prominent physician-naturalists included Alexander Garden (for whom the gardenia is named), John Edwards Holbrook ("father of American herpetology"), and Francis Peyre Porcher (whose Resources of Southern Fields and Forests helped Confederates compensate for drug shortages). The Charleston physician-naturalists belonged to an "aristocracy of talent" as distinguished from the "aristocracy of wealth" of lowcountry planters, who probably did more than any other group to perpetuate slavery and propel the South toward a disastrous civil war. None of the physician-naturalists actively opposed slavery or secession, a reminder that we are all prisoners of the prevailing paradigms and prejudices of our times. PMID- 25125747 TI - TGFBR1 and cancer susceptibility. AB - Transforming growth factor beta (TGF-beta) is a potent inhibitor of cell growth. TGFBR1 6A is a polymorphism consisting of a 9-base pair in-frame deletion within exon 1 of the type I TGF-beta receptor (TGFBR1), which results in a receptor with decreased TGF-beta signaling capability. The discovery of an association between TGFBR1*6A and cancer susceptibility led to the hypothesis that hypomorphic variants of the TGF-beta signaling pathway may predispose to the development of cancer. This hypothesis was tested in vivo with the development of a mouse model of Tgfbr1 haploinsufficiency. Tgfbr1 (+/-) mice developed twice as many intestinal tumors as Tgfbr1 (+/+). Tgfbr1 haploinsufficiency was also associated with early onset adenocarcinoma and increased tumor cell proliferation. A case control study identified two haplotypes associated with constitutively decreased TGFBR1 and substantially increased colorectal cancer risk indicating that TGFBR1 may act as a potent modifier of cancer risk. PMID- 25125749 TI - Can visual arts training improve physician performance? AB - Clinical educators use medical humanities as a means to improve patient care by training more self-aware, thoughtful, and collaborative physicians. We present three examples of integrating fine arts - a subset of medical humanities - into the preclinical and clinical training as models that can be adapted to other medical environments to address a wide variety of perceived deficiencies. This novel teaching method has promise to improve physician skills, but requires further validation. PMID- 25125756 TI - Secretary-Treasurer's report: the 126(th) meeting held at The Charleston Place Hotel Charleston, South Carolina October 17(th) through October 20(th), 2013. PMID- 25125757 TI - Accountants' compilation report to the board of trustees: American Clinical and Climatological Association, Baton Rouge, Louisiana. PMID- 25125750 TI - Using 2-photon microscopy to understand albuminuria. AB - Intravital 2-photon microscopy, along with the development of fluorescent probes and innovative software, has rapidly advanced the study of intracellular and intercellular processes at the organ level. Researchers can quantify the distribution, behavior, and dynamic interactions of up to four labeled chemical probes and proteins simultaneously and repeatedly in four dimensions (3D + time) with subcellular resolution in real time. Transgenic fluorescently labeled proteins, delivery of plasmids, and photo-activatable probes enhance these possibilities. Thus, multi-photon microscopy has greatly extended our ability to understand cell biology intra-vitally at cellular and subcellular levels. For example, evaluation of rat surface glomeruli and accompanying proximal tubules has shown the long held paradigm regarding limited albumin filtration under physiologic conditions is to be questioned. Furthermore, the role of proximal tubules in determining albuminuria under physiologic and disease conditions was supported by direct visualization and quantitative analysis. PMID- 25125751 TI - Role of inflammation and inflammatory mediators in colorectal cancer. AB - Chronic inflammation is a risk factor for several different cancers including colorectal cancer (CRC). However, the mechanisms underlying the contribution of inflammation to cancer remain elusive. Pro-inflammatory mediators such as cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) contribute to cancer progression. Here, we show that COX-2 is an immediate-early response gene induced by growth factors and pro-inflammatory cytokines and its levels are elevated in human CRCs. Furthermore, we show that COX-2-derived PGE2 promotes colonic tumor growth via silencing certain tumor suppressors and DNA repair genes by DNA methylation in colonic epithelial tumor cells. We also report that C-X-C motif chemokine receptor 2 accelerates colonic inflammation and colitis-associated tumorigenesis by mediating myeloid-derived suppressor cell recruitment to the tumor microenvironment. These findings not only support a rationale to target these pro-inflammatory pathways for cancer prevention and treatment but also provide support for developing new therapeutic approaches to subvert chronic inflammation- and tumor-induced immunosuppression. PMID- 25125767 TI - Adaptive Multivariate Global Testing. AB - We present a methodology for dealing with recent challenges in testing global hypotheses using multivariate observations. The proposed tests target situations, often arising in emerging applications of neuroimaging, where the sample size n is relatively small compared with the observations' dimension K. We employ adaptive designs allowing for sequential modifications of the test statistics adapting to accumulated data. The adaptations are optimal in the sense of maximizing the predictive power of the test at each interim analysis while still controlling the Type I error. Optimality is obtained by a general result applicable to typical adaptive design settings. Further, we prove that the potentially high-dimensional design space of the tests can be reduced to a low dimensional projection space enabling us to perform simpler power analysis studies, including comparisons to alternative tests. We illustrate the substantial improvement in efficiency that the proposed tests can make over standard tests, especially in the case of n smaller or slightly larger than K. The methods are also studied empirically using both simulated data and data from an EEG study, where the use of prior knowledge substantially increases the power of the test. Supplementary materials for this article are available online. PMID- 25125768 TI - Differences by mother's education in the effect of childcare on child obesity. AB - Previous studies have found adverse effects of maternal employment on child obesity for higher educated mothers. Using a quasi-structural model, we find additionally a lower risk of obesity for children of less educated mothers with increased time in non-parental childcare. PMID- 25125766 TI - Alcohol Environment, Perceived Safety, and Exposure to Alcohol, Tobacco, and Other Drugs in Early Adolescence. AB - This study examined the association between the count of alcohol outlets around children's homes and opportunities to use alcohol, tobacco, and other drugs (ATOD) during pre-adolescence. Data were collected in 2007 from 394 Baltimore City children aged 8-13 (86% African American). Participants' residential address and alcohol outlet data were geocoded with quarter mile (i.e., walking distance) buffers placed around each participant's home to determine the number of outlets within walking distance. The unadjusted logistic regression models revealed that each unit increase in the number of alcohol outlets was associated with a 14% increase in the likelihood of children seeing people selling drugs (OR=1.14, p=.04) and a 15% increase in the likelihood of seeing people smoking marijuana (OR=1.15, p<.01). After adjusting for neighborhood physical disorder, the relationship between alcohol outlets and seeing people selling drugs and seeing people smoking marijuana was fully attenuated. These results suggest that alcohol outlets are one aspect of the larger environmental context that is related to ATOD exposure in children. Future studies should examine the complex relationship between neighborhood physical disorder and the presence of alcohol outlets. PMID- 25125769 TI - Permanency Outcomes for Toddlers in Child Welfare Two Years After a Randomized Trial of a Parenting Intervention. AB - This study reports on child welfare outcomes of a community based, randomized control trial of Promoting First Relationships(r) (PFR; Kelly, Sandoval, Zuckerman, & Buehlman, 2008), a 10-week relationship-based home visiting program, on stability of children's placements and permanency status two years after enrollment into the study. Toddlers 10 - 24 months (N = 210) with a recent placement disruption were randomized, along with their birth or foster/kin parents, to PFR (n = 105) or a comparison condition (n = 105). A stable placement had no interruptions or disruptions. A permanent placement was a stable placement ending with a legal discharge to the study caregiver. Logistic regression models predicting the dichotomous stability and permanency variables, controlling for caregiver type, child welfare variables, and caregiver commitment, were conducted. There was no difference by intervention group on stability or permanency, but there was a significant interaction between caregiver type (birth parent vs. foster/kin) and intervention group. More foster/kin caregivers who received the PFR intervention provided stable, uninterrupted care and eventually adopted or became the legal guardians of the toddlers in their care, compared to foster/kin caregivers randomized to the comparison condition. PMID- 25125770 TI - Psychology and the Rationality of Emotion. AB - Questions addressed by recent psychological research on emotion include questions about how thought shapes emotion and how emotion, in turn, shapes thought. Research on emotion and cognition paints a somewhat different picture than that seen in traditional discussions of passion and reason. This article reviews several aspects of this research, concentrating specifically on three views of rationality: Rationality as Process, Rationality as Product, and Rationality as Outcome. PMID- 25125771 TI - Perceptual and cognitive biases in individuals with body dysmorphic disorder symptoms. AB - Given the extreme focus on perceived physical defects in body dysmorphic disorder (BDD), we expected that perceptual and cognitive biases related to physical appearance would be associated with BDD symptomology. To examine these hypotheses, participants (N = 70) high and low in BDD symptoms completed tasks assessing visual perception and cognition. As expected, there were significant group differences in self-, but not other-, relevant cognitive biases. Perceptual bias results were mixed, with some evidence indicating that individuals high (versus low) in BDD symptoms literally see themselves in a less positive light. Further, individuals high in BDD symptoms failed to demonstrate a normative self enhancement bias. Overall, this research points to the importance of assessing both cognitive and perceptual biases associated with BDD symptoms, and suggests that visual perception may be influenced by non-visual factors. PMID- 25125772 TI - Emotion expression among abusive mothers is associated with their children's emotion processing and problem behaviours. AB - The current study evaluated the quality of facial and vocal emotional expressions in abusive and non-abusive mothers, and assessed whether mothers' emotional expression quality was related to their children's cognitive processing of emotion and behavioural problems. Relative to non-abusive mothers, abusive mothers produced less prototypical angry facial expressions, and less prototypical angry, happy, and sad vocal expressions. The intensity of mothers' facial and vocal expressions of anger was related to their children's externalising and internalising symptoms. Additionally, children's cognitive processing of their mothers' angry faces was related to the quality of mothers' facial expressions. Results are discussed with respect to the impact of early emotional learning environments on children's socioemotional development and risk for psychopathology. PMID- 25125773 TI - Equilibrium Conformations of Concentric-tube Continuum Robots. AB - Robots consisting of several concentric, preshaped, elastic tubes can work dexterously in narrow, constrained, and/or winding spaces, as are commonly found in minimally invasive surgery. Previous models of these "active cannulas" assume piecewise constant precurvature of component tubes and neglect torsion in curved sections of the device. In this paper we develop a new coordinate-free energy formulation that accounts for general preshaping of an arbitrary number of component tubes, and which explicitly includes both bending and torsion throughout the device. We show that previously reported models are special cases of our formulation, and then explore in detail the implications of torsional flexibility for the special case of two tubes. Experiments demonstrate that this framework is more descriptive of physical prototype behavior than previous models; it reduces model prediction error by 82% over the calibrated bending-only model, and 17% over the calibrated transmissional torsion model in a set of experiments. PMID- 25125774 TI - The Knowledge Broker's "Fit" in the World of Knowledge Translation. PMID- 25125775 TI - Lower-limb kinematics of single-leg squat performance in young adults. AB - PURPOSE: To determine the kinematic parameters that characterize good and poor single-leg squat (SLS) performance. METHODS: A total of 22 healthy young adults free from musculoskeletal impairment were recruited for testing. For each SLS, both two-dimensional video and three-dimensional motion analysis data were collected. Pelvis, hip, and knee angles were calculated using a reliable and validated lower-limb (LL) biomechanical model. Two-dimensional video clips of SLSs were blindly assessed in random order by eight musculoskeletal physiotherapists using a 10-point ordinal scale. To facilitate between-group comparisons, SLS performances were stratified by tertiles corresponding to poor, intermediate, and good SLS performance. RESULTS: Mean ratings of SLS performance assessed by physiotherapists were 8.3 (SD 0.5), 6.8 (SD 0.7), and 4.0 (SD 0.8) for good, intermediate, and poor squats, respectively. Three-dimensional analysis revealed that people whose SLS performance was assessed as poor exhibited increased hip adduction, reduced knee flexion, and increased medio-lateral displacement of the knee joint centre compared to those whose SLS performance was assessed as good (p<=0.05). CONCLUSIONS: Overall, poor SLS performance is characterized by inadequate knee flexion and excessive frontal plane motion of the knee and hip. Future investigations of SLS performance should consider standardizing knee flexion angle to illuminate other influential kinematic parameters. PMID- 25125776 TI - Understanding physiotherapists' roles in ontario primary health care teams. AB - PURPOSE: To understand physiotherapists' roles and how they are enacted within Ontario primary health care (PHC) teams. METHODS: Following a pragmatic grounded theory approach, 12 physiotherapists practising within Ontario PHC teams participated in 18 semi-structured in-depth in-person interviews. All interviews were audiotaped and transcribed verbatim, then entered into NVIVO-8. Coding followed three progressive analytic stages and was iterative in nature, guided by grounded theory. An explanatory scheme was developed. RESULTS: Physiotherapists negotiate their place within the PHC teams through five interrelated roles: (1) manager; (2) evaluator; (3) collaborator; (4) educator; and (5) advocate. These five roles are influenced by three contextual layers: (1) inter-professional team; (2) community and population served; and (3) organizational structure and funding. Canada's PHC mandate (access, teams, information, and healthy living) frame the contexts that influence role enactment. CONCLUSIONS: To fulfill the PHC mandate, physiotherapists carry out multiple roles that are based on a broad holistic perspective of health, within the context of a collaborative inter professional team and the community, through an evidenced-informed approach to care. There appear to be multiple ways of successfully integrating physiotherapists within PHC teams, provided that role enactment is context sensitive and congruent with the mandate of PHC. PMID- 25125777 TI - Reliability and validity of two versions of the upper extremity functional index. AB - PURPOSE: To examine the reliability, validity, and sensitivity to change of the 20-item version and the Rasch-refined 15-item version of the Upper Extremity Functional Index (UEFI-20 and UEFI-15, respectively) and to determine the impact of arm dominance on the positive minimal clinically important difference (pMCID). METHODS: Adults with upper-extremity (UE) dysfunction completed the UEFI-20, Upper Extremity Functional Scale (UEFS), Pain Limitation Scale, and Pain Intensity Scale at their initial physiotherapy assessment (Time 1); 24-48 hours later (Time 2); and 3 weeks into treatment or at discharge, whichever came first (Time 3). Demographics, including working status, were obtained at Time 1. Global ratings of change (GRC) were provided by the treating physiotherapist and patient at Time 3. The UEFI-15 was calculated from relevant items in the UEFI-20. The intra-class correlation coefficient (ICC) and minimal detectable change (MDC) quantified test-retest reliability (Time 1-Time 2). Cross-sectional convergent validity was determined by the association (Pearson's r) between Time 1 measures of function and pain. Known-groups validity was evaluated with a one-way ANOVA across three levels of working status. Longitudinal validity was determined by the association (Pearson's r) between function and pain change scores (Time 1 Time 3). Receiver operating characteristic (ROC) curves estimated the pMCID using Time 1-Time 3 change scores and average patient/therapist GRC. RESULTS: Reliability for the UEFI-20 and UEFI-15 was the same (ICC=0.94 for both measures). MDC values were 9.4/80 for the UEFI-20 and 8.8/100 for the UEFI-15. Cross-sectional, known-groups, and longitudinal validity were confirmed for both UEFI measures. pMCID values were 8/80 for the UEFI-20 and 6.7/100 for the UEFI 15; pMCID was higher for people whose non-dominant arm was affected. CONCLUSIONS: Both UEFI measures show acceptable reliability and validity. Arm dominance affects pMCID. The UEFI-15 is recommended because it measures only one dimension: UE function. PMID- 25125778 TI - Physiotherapists' perceptions of and experiences with the discharge planning process in acute-care general internal medicine units in ontario. AB - PURPOSE: To examine discharge planning of patients in general internal medicine units in Ontario acute-care hospitals from the perspective of physiotherapists. METHODS: A cross-sectional study using an online questionnaire was sent to participants in November 2011. Respondents' demographic characteristics and ranking of factors were analyzed using descriptive statistics; t-tests were performed to determine between-group differences (based on demographic characteristics). Responses to open-ended questions were coded to identify themes. RESULTS: Mobility status was identified as the key factor in determining discharge readiness; other factors included the availability of social support and community resources. While inter-professional communication was identified as important, processes were often informal. Discharge policies, timely availability of other discharge options, and pressure for early discharge were identified as affecting discharge planning. Respondents also noted a lack of training in discharge planning; accounts of ethical dilemmas experienced by respondents supported these themes. CONCLUSIONS: Physiotherapists consider many factors beyond the patient's physical function during the discharge planning process. The improvement of team communication and resource allocation should be considered to deal with the realities of discharge planning. PMID- 25125779 TI - Patients' perceptions of navigating "the system" for arthritis management: are they able to follow our recommendations? AB - PURPOSE: To understand whether a visit to a Hip/Knee Arthritis Assessment Centre (AC), where non-surgical candidates with arthritis are directed toward community resources and provided with a conservative treatment "prescription," contributes to patients' self-management and ability to access community resources. METHODS: A purposive sample of non-surgical patients was contacted 3-10 months after their AC visit. Three focus groups (n=20) and 20 semi-structured telephone interviews were conducted. Transcripts were systematically coded and analyzed using a qualitative descriptive research methodology. RESULTS: While participants generally reported that the AC visit improved self-management, analysis identified an emergent theme about the inadequacy of conservative management in general, subdivided into two sub-themes related to (1) limited access to high quality, non-surgical treatment, such as physiotherapy and (2) health care providers' attitudes and approaches, which do not embrace chronic disease prevention and management. CONCLUSIONS: An AC visit contributes to arthritis self management; however, the current health care system does not adequately support conservative treatment of chronic conditions. Treatment guidelines need to be tailored to the local health care context in which they are applied. PMID- 25125780 TI - Clinician's Commentary on Winter Di Cola et al.(1.). PMID- 25125783 TI - Clinician's Commentary on Duong et al.(1.). PMID- 25125782 TI - Developing a physiotherapy-specific preliminary clinical decision-making tool for oxygen titration: a modified delphi study. AB - PURPOSE: To develop and evaluate a preliminary clinical decision-making tool (CDMT) to assist physiotherapists in titrating oxygen for acutely ill adults in Ontario. METHODS: A panel of 14 experienced cardiorespiratory physiotherapists was recruited. Factors relating to oxygen titration were identified using a modified Delphi technique. Four rounds of questionnaires were conducted, during which the goals were to (1) generate factors, (2) reduce factors and debate contentious factors, (3) finalize factors and develop the preliminary CDMT, and (4) evaluate the usability of the tool in a clinical context. RESULTS: The panel reached consensus on a total of 89 factors, which were compiled to create the preliminary CDMT. The global tool reached consensus for sensibility, receiving a mean score of 6/7 on a 7-point Likert-type scale (1=unacceptable; 7=excellent). Five of the nine individual components of evaluation of the tool achieved scores >=6.0; the remaining four had mean scores between 5.4 and 5.9. CONCLUSION: This study produced a preliminary CDMT for oxygen titration, which the panel agreed was highly comprehensible and globally sensible. Further research is necessary to evaluate the sensibility and applicability of the tool in a clinical setting. PMID- 25125781 TI - A survey of physiotherapists' experience using outcome measures in total hip and knee arthroplasty. AB - PURPOSE: To identify physiotherapists' familiarity with and experience using outcome measures (OMs) along the care continuum for patients undergoing total joint arthroplasty (TJA) of the hip and knee. Views on future use and barriers were also captured. METHODS: A stratified random sample of physiotherapists in one Canadian province completed a questionnaire about 19 standardized and clinically feasible OMs. Analyses included descriptive statistics and chi-square and McNemar tests to compare use of OMs for clinical decision making and program evaluation. RESULTS: Of 694 physiotherapists surveyed, 298 (43%) responded. Of these, 172 (58%) treated TJA clients and completed the full questionnaire. A majority worked in public practice settings and >1 care phase (e.g., pre-op, acute, rehab). All physiotherapists reported using >=1 OM and having greater experience using performance-based measures than patient-reported OMs. OMs were used more often for clinical decision making than for program evaluation. Dissatisfaction with available tools was evident from respondents' comments. Several barriers to using OMs were identified in varied clinical settings and care phases. CONCLUSIONS: While physiotherapists use a variety of OMs along the TJA continuum, there remain challenges to routine use across clinical settings, care phases, and patient sub-groups. PMID- 25125784 TI - Contact with Young Adults with Disability Led to a Positive Change in Attitudes toward Disability among Physiotherapy Students. AB - PURPOSE: To determine whether contact over 8 weeks with a person with disability benefits physiotherapy students' attitudes toward disability and their development of professional behaviours and skills. METHODS: Sixteen adults with Down syndrome were matched with 16 physiotherapy students (13 women, 3 men; mean age 22.5 [SD 3.0] years) and randomized to either an 8-week, twice-weekly walking programme or an 8-week, once-weekly social activities programme. Students completed the Interaction with Disabled Persons scale, the Community Living Attitudes scale, and the Barriers to Exercise scale and rated their competency in professional behaviours and skills. RESULTS: There were no differences between the groups for any outcome. Across both groups, students showed positive changes in attitudes toward disability, self-ratings of professional behaviours, and confidence in working with people with disability. CONCLUSIONS: After an 8-week programme, physiotherapy students reported being more comfortable with and having more confidence in working with people with disability. These data support the idea that contact with people with disability in community settings has positive benefits for physiotherapy students, regardless of the content of the experience. PMID- 25125785 TI - Clinicians' commentary on shields and taylor(1.). PMID- 25125786 TI - An Improvised "Blow Glove" Device Produces Similar PEP Values to a Commercial PEP Device: An Experimental Study. AB - BACKGROUND: Postoperative positive expiratory pressure (PEP) therapy promotes increased lung volume, secretion clearance, and improved oxygenation. Several commercial devices exist that produce recommended PEP values (10-20 cmH2O) when the patient breathes through a fixed orifice resistor. It was hypothesized that an inexpensive, improvised "blow glove" device would produce similar PEP values over a wider range of expiration volumes and flow rates. METHODS: PEP for different expiration volumes (400-2000 mL) and expiratory flow rates (10-80 L/min) was compared between a commercial PEP device (Resistex, Mercury Medical, Clearwater, FL) and an improvised "blow glove" device, recorded by a Vela ventilator (CareFusion, San Diego, CA). Dynamics in positive end expiratory pressure (PEEP) values were evaluated following five consecutive expirations. The "blow glove" device was evaluated using various glove compositions and sizes. RESULTS: The improvised "blow glove" device produced a significantly higher rate of PEP values in the recommended range than the Resistex device (88.9% vs. 20%, p<0.0001). No significant difference was observed between small and large glove sizes (88.9% vs. 82.9%, p>0.05), but the powdered latex glove showed a significantly higher rate of PEP values in the recommended range than the powder free latex glove (88.9% vs. 44.4%, p<0.001). CONCLUSIONS: A "blow glove" PEP device using a powdered latex glove produces PEP values in the recommended range over a wider spectrum of expiratory flow rates and expiration volumes than a commercial PEP device. PMID- 25125789 TI - Clinician's Commentary on Anderson et al.(1.). PMID- 25125788 TI - What clinical instructors want: perspectives on a new assessment tool for students in the clinical environment. AB - PURPOSE: Many Canadian physical therapy education programs use the 1997 version of the Physical Therapist Clinical Performance Instrument (PT-CPI) to evaluate students in their clinical placements. Recent evidence that clinical instructors (CIs) are unsatisfied with the PT-CPI, however, suggests a need to develop a new assessment tool. The purpose of this study was to gather Canadian CIs' perspectives on rating scales, preferred training methods, and format for future tool development. METHODS: This qualitative descriptive study involved five focus groups from across Canada. English-speaking CIs who had supervised at least one Canadian student in clinical practice were eligible for the study. RESULTS: Participants identified concerns with the PT-CPI and indicated a preference for (1) more objective rating scales with clearly defined anchors, (2) both in-person and online training methods for CIs, and (3) a tool that could be completed and reviewed on paper or online. CONCLUSIONS: CIs affirmed the need to develop a new assessment tool. RESULTS of the study will be used to inform the development of a new assessment tool to better evaluate Canadian physical therapy students' performance in the clinical setting. PMID- 25125787 TI - The Development and Testing of a Checklist to Study Behaviour Change Techniques used in a Treatment Programme for Canadian Armed Forces Members with Chronic Non specific Low Back Pain. AB - PURPOSE: There are reports of increased use of a variety of behaviour change techniques (BCT) by physiotherapists and findings of beneficial effects of use. However, there is a lack of physiotherapy-specific definitions of these techniques, as well as a sense of how physiotherapists use them in practice. Through this study, the authors created and field tested a preliminary nomenclature and description for BCT in patients with chronic non-specific low back pain (CNSLBP). METHODS: Items for the Physiotherapy Behaviour Change Technique (PT-BCT) checklist were derived from a nomenclature created for use in psychology and also from publications of studies using cognitive behaviour therapy-based approaches in physiotherapy. Content validity was tested via survey of clinical and research experts. Videotapes of a 6-week patient self-management rehabilitation programme were used for training, reliability testing, and field testing of the PT-BCT checklist. RESULTS: Checklist items were endorsed by the majority of experts surveyed; intra- and inter-rater reliability were moderate to high. In the field study, a broad range of BCT types (behavioural, cognitive, and motivational) were observed in both classroom and gym settings. CONCLUSIONS: The BCT nomenclature arising from this study and the PT-BCT checklist will be useful to further explore behaviour change in physiotherapy practice. The observation in this study that BCT were integrated into physiotherapists' practice illustrates how physiotherapists can play a role in changing behaviour, specifically in the presence of CNSLBP. PMID- 25125790 TI - What Does the Cochrane Collaboration Say about Exercises for Osteoarthritis? PMID- 25125791 TI - Frustrated Freedom: The Effects of Agency and Wealth on Wellbeing in Rural Mozambique. AB - In Sen's capability view of poverty, wellbeing is threatened by both deficits of wealth and deficits of individual agency. Sen further predicts that "unfreedom," or low levels of agency will suppress the wellbeing effects of higher levels of wealth. The current paper extends Sen's view to include a condition, labeled "frustrated freedom," in which relatively higher levels of agency can heighten the poverty effects of relatively low levels of material wealth. Applying data from a large scale population study of female heads of household in rural Mozambique, the paper empirically tests Sen's view and the proposed extension. As predicted, agency is found to moderate the relationship between agency, wealth, and wellbeing, uncovering evidence of both unfreedom and frustrated freedom in the population. Further research into the complex dynamics of wellbeing and poverty are called for by the authors. PMID- 25125792 TI - Adhesion Force Measurements Using an Atomic Force Microscope Upgraded with a Linear Position Sensitive Detector. AB - The atomic force microscope (AFM), in addition to providing images on an atomic scale, can be used to measure the forces between surfaces and the AFM probe. The potential uses of mapping the adhesive forces on the surface include a spatial determination of surface energy and a direct identification of surface proteins through specific protein-ligand binding interactions. The capabilities of the AFM to measure adhesive forces can be extended by replacing the four-quadrant photodiode detection sensor with an external linear position sensitive detector and by utilizing a dedicated user-programmable signal generator and acquisiton system. Such an upgrade enables the microscope to measure in the larger dynamic range of adhesion forces, improves the sensitivity and linearity of the measurement, and eliminates the problems inherent to the multiple repetitious contacts between the AFM probe and the specimen surface. PMID- 25125793 TI - Effects of Discrete Protein-Surface Interactions in Scanning Force Microscopy Adhesion Force Measurements. AB - The potential for measuring specific molecular recognition forces between probe bound ligands and surface-bound proteins using a scanning force microscope (SFM) has recently gained much attention. Generally, observed discontinuities in the SFM force-displacement curves are attributed to the breaking of discrete, specific affinity bonds. The present study on the molecular recognition system composed of surface-immobilized antifluorescyl IgG molecules and SFM probe-bound fluorescein ligands has demonstrated that similar intermittent discontinuities in the SFM force-displacement curves may in fact be largely due to nonspecific discrete interactions between the protein and the SFM probe. The mechanical behavior of the cantilever-spherical bead system used in this study is discussed, as it appears to cause a false indication of the separation distance between the surface and probe. The strong lateral interactions which result in "stick and slip"-like discontinuities seen in the adhesion curves are likely the result of localized adhesion due to the heterogeneous nature of proteins and the lack of molecular mobility allowed in the experimental system. The effect is magnified with increasing contact time between the protein and probe. Factors which may cause such anomalous behavior in a specific ligand-protein system are discussed in order to avoid misinterpretation of SFM adhesion measurements. PMID- 25125794 TI - In-Situ Atomic Force Microscope Imaging of Calcite Etch Pit Morphology Changes in Undersaturated and 1-Hydroxyethylidene-1,1-diphosphonic Acid Poisoned Solutions. AB - Morphology changes in etch pits formed on the (1014) cleavage plane of calcite were induced by varying the ratio of [Ca2+] to [CO32-] in the bulk solution as well as through the addition of the crystal poison 1-hydroxyethylidene-1,1 diphosphonic acid (HEDP). Three distinct morphologies were noted: symmetric rhombic, asymmetric rhombic, and triangular with a rough curved hypotenuse. The latter represents a transient morphology which is only observed during the actual dissolution process, while the former morphologies persist after dissolution is halted. PMID- 25125795 TI - Human Growth Hormone Adsorption Kinetics and Conformation on Self-Assembled Monolayers. AB - The adsorption process of the recombinant human growth hormone on organic films, created by self-assembly of octadecyltrichlorosilane, arachidic acid, and dipalmitoylphosphatidylcholine, is investigated and compared to adsorption on silica and methylated silica substrates. Information on the adsorption process of human growth hormone (hGH) is obtained by using total internal reflection fluorescence (TIRF). The intensity, spectra, and quenching of the intrinsic fluorescence emitted by the growth hormone's single tryptophan are monitored and related to adsorption kinetics and protein conformation. For the various alkylated hydrophobic surfaces with differences in surface density and conformational freedom it is observed that the adsorbed amount of growth hormone is relatively large if the alkyl chains are in an ordered structure while the amounts adsorbed are considerably lower for adsorption onto less ordered alkyl chains of fatty acid and phospholipid layers. Adsorption on methylated surfaces results in a relatively large conformational change in the growth hormone's structure, as displayed by a 7 nm blue shift in emission wavelength and a large increase in the effectiveness of fluorescence quenching. Conformational changes are less evident for hGH adsorption onto the fatty acid and phospholipid alkyl chains. Adsorption kinetics on the hydrophilic head groups of the self-assembled monolayers are similar to those on solid hydrophilic surfaces. The relatively small conformational changes in the hGH structure observed for adsorption on silica are even further reduced for adsorption on fatty acid head groups. PMID- 25125796 TI - Validation of a flow-structure-interaction computation model of phonation. AB - Computational models of vocal fold (VF) vibration are becoming increasingly sophisticated, their utility currently transiting from exploratory research to predictive research. However, validation of such models has remained largely qualitative, raising questions over their applicability to interpret clinical situations. In this paper, a computational model with a segregated implementation is detailed. The model is used to predict the fluid-structure interaction (FSI) observed in a physical replica of the VFs when it is excited by airflow. Detailed quantitative comparisons are provided between the computational model and the corresponding experiment. First, the flow model is separately validated in the absence of VF motion. Then, in the presence of flow-induced VF motion, comparisons are made of the flow pressure on the VF walls and of the resulting VF displacements. Self-similarity of spatial distributions of flow pressure and VF displacements is highlighted. The self-similarity leads to normalized pressure and displacement profiles. It is shown that by using linear superposition of average and fluctuation components of normalized computed displacements, it is possible to determine displacements in the physical VF replica over a range of VF vibration conditions. Mechanical stresses in the VF interior are related to the VF displacements, thereby the computational model can also determine VF stresses over a range of phonation conditions. PMID- 25125797 TI - Novel procedure for thermal equilibration in molecular dynamics simulation. AB - We describe a simple novel procedure for achieving thermal equilibration between a protein and a surrounding solvent during molecular dynamics (MD) simulation. The method uniquely defines the length of simulation time required to achieve thermal equilibrium over a broad range of parameters, thus removing ambiguities associated with the traditional heuristic approaches. The proposed protocol saves simulation time and avoids bias introduced by the inclusion of non-equilibrium events. The key element of the procedure involves coupling only the solvent atoms to a standard heat bath. Measuring progress towards thermal equilibration involves simply monitoring the difference in temperature between the solvent and the protein. Here, we report that the results of MD simulations using the above procedure are measurably improved relative to the traditional approaches in terms of root-mean-square deviations and principal components analysis both indicating significantly less undesirable divergence. PMID- 25125798 TI - Testing Scientific Software: A Systematic Literature Review. AB - CONTEXT: Scientific software plays an important role in critical decision making, for example making weather predictions based on climate models, and computation of evidence for research publications. Recently, scientists have had to retract publications due to errors caused by software faults. Systematic testing can identify such faults in code. OBJECTIVE: This study aims to identify specific challenges, proposed solutions, and unsolved problems faced when testing scientific software. METHOD: We conducted a systematic literature survey to identify and analyze relevant literature. We identified 62 studies that provided relevant information about testing scientific software. RESULTS: We found that challenges faced when testing scientific software fall into two main categories: (1) testing challenges that occur due to characteristics of scientific software such as oracle problems and (2) testing challenges that occur due to cultural differences between scientists and the software engineering community such as viewing the code and the model that it implements as inseparable entities. In addition, we identified methods to potentially overcome these challenges and their limitations. Finally we describe unsolved challenges and how software engineering researchers and practitioners can help to overcome them. CONCLUSIONS: Scientific software presents special challenges for testing. Specifically, cultural differences between scientist developers and software engineers, along with the characteristics of the scientific software make testing more difficult. Existing techniques such as code clone detection can help to improve the testing process. Software engineers should consider special challenges posed by scientific software such as oracle problems when developing testing techniques. PMID- 25125799 TI - Print-to-Pattern Dry Film Photoresist Lithography. AB - Here we present facile microfabrication processes, referred to as Print-to Pattern dry film photoresist (DFP) lithography, that utilize the combined advantages of wax printing and DFP to produce micropatterned substrates with high resolution over a large surface area in a non-cleanroom setting. The Print-to Pattern methods can be performed in an out-of-cleanroom environment making microfabrication much more accessible to minimally equipped laboratories. Two different approaches employing either wax photomasks or wax etchmasks from a solid ink desktop printer have been demonstrated that allow the DFP to be processed in a negative tone or positive tone fashion, respectively, with resolutions of 100 MUm. The effect of wax melting on resolution and as a bonding material was also characterized. In addition, solid ink printers have the capacity to pattern large areas with high resolution which was demonstrated by stacking DFP layers in a 50 mm * 50 mm woven pattern with 1 mm features. By using an office printer to generate the masking patterns, the mask designs can be easily altered in a graphic user interface to enable rapid prototyping. PMID- 25125802 TI - Rapid on-site cytological evaluation of transbronchial needle aspiration: Why not? PMID- 25125800 TI - Opposing roles of leptin and ghrelin in the equine corpus luteum regulation: an in vitro study. AB - Metabolic hormones have been associated with reproductive function modulation. Thus, the aim of this study was: (i) to characterize the immunolocalization, mRNA and protein levels of leptin (LEP), Ghrelin (GHR) and respective receptors LEPR and Ghr-R1A, throughout luteal phase; and (ii) to evaluate the role of LEP and GHR on progesterone (P4), prostaglandin (PG) E2 and PGF2alpha , nitric oxide (nitrite), tumor necrosis factor-alpha (TNF); macrophage migration inhibitory factor (MIF) secretion, and on angiogenic activity (BAEC proliferation), in equine corpus luteum (CL) from early and mid-luteal stages. LEPR expression was decreased in late CL, while GHR/Ghr-R1A system was increased in the same stage. Regarding secretory activity, GHR decreased P4 in early CL, but increased PGF2alpha , nitrite and TNF in mid CL. Conversely, LEP increased P4, PGE2, angiogenic activity, MIF, TNF and nitrite during early CL, in a dose-dependent manner. The in vitro effect of LEP on secretory activity was reverted by GHR, when both factors acted together. The present results evidence the presence of LEP and GHR systems in the equine CL. Moreover, we suggest that LEP and GHR play opposing roles in equine CL regulation, with LEP supporting luteal establishment and GHR promoting luteal regression. Finally, a dose-dependent luteotrophic effect of LEP was demonstrated. PMID- 25125801 TI - Cholecystokinin inhibits inducible nitric oxide synthase expression by lipopolysaccharide-stimulated peritoneal macrophages. AB - Cholecystokinin (CCK) was first described as a gastrointestinal hormone. However, apart from its gastrointestinal effects, studies have described that CCK also plays immunoregulatory roles. Taking in account the involvement of inducible nitric oxide synthase- (iNOS-) derived NO in the sepsis context, the present study was undertaken to investigate the role of CCK on iNOS expression in LPS activated peritoneal macrophages. Our results revealed that CCK reduces NO production and attenuates the iNOS mRNA expression and protein formation. Furthermore, CCK inhibited the nuclear factor- (NF-) kappaB pathway reducing IkappaBalpha degradation and minor p65-dependent translocation to the nucleus. Moreover, CCK restored the intracellular cAMP content activating the protein kinase A (PKA) pathway, which resulted in a negative modulatory role on iNOS expression. In peritoneal macrophages, the CCK-1R expression, but not CCK-2R, was predominant and upregulated by LPS. The pharmacological studies confirmed that CCK-1R subtype is the major receptor responsible for the biological effects of CCK. These data suggest an anti-inflammatory role for the peptide CCK in modulating iNOS-derived NO synthesis, possibly controlling the macrophage activation through NF-kappaB, cAMP-PKA, and CCK-1R pathways. Based on these findings, CCK could be used as an adjuvant agent to modulate the inflammatory response and prevent systemic complications commonly found during sepsis. PMID- 25125803 TI - Mycobacterium and sarcoidosis: Old wine in a new bottle. PMID- 25125804 TI - Diagnostic utility of conventional transbronchial needle aspiration without rapid on-site evaluation in patients with lung cancer. AB - BACKGROUND: Endobronchial involvement is frequently absent in many patients with bronchogenic carcinoma. Malignant involvement may be confined to lymph nodes/peribronchial locations only or may be present along with endobronchial lesions. Transbronchial needle aspiration (TBNA) is a flexible bronchoscopic technique which can be employed to obtain tissue samples from mediastinal lymph nodes or peribronchial locations. Although a safe and cost effective bronchoscopic modality, it is frequently underutilized owing to concerns regarding its diagnostic utility and safety. Herein, we describe our experience over 1 year on the diagnostic utility of TBNA without rapid on-site evaluation (ROSE) in patients with suspected diagnosis of lung cancer. MATERIALS AND METHODS: We retrospectively reviewed the cases in which conventional TBNA-without ROSE was performed for suspected lung cancer, between January 2012 and December 2012. Each lymph node station from which aspiration was performed was sampled thrice and smears were prepared on slides which were later examined by a cytopathologist. RESULTS: Twenty-six cases were retrieved in which conventional TBNA without ROSE for suspected lung cancer with mediastinal involvement was performed during the study period. Adequate lymph node sampling could be achieved in 57.7% cases. Conventional TBNA was diagnostic in 11 out of the 26 (42.3%) patients. The diagnostic yield improved to 73.3% in patients in whom an adequate lymph nodal sample could be obtained. TBNA was the sole diagnostic sample in six (54.5%) patients. Alternative diagnoses (sarcoidosis and tuberculosis) were obtained in two patients. CONCLUSION: Conventional TBNA without ROSE is a safe and efficacious flexible bronchoscopic procedure which should be performed routinely from bronchoscopically accessible locations in patients with a suspected diagnosis of lung cancer. PMID- 25125805 TI - Vitamin D status in adult critically ill patients in Eastern India: An observational retrospective study. AB - BACKGROUND: The prevalence of vitamin D deficiency in critically ill patients has been reported to be as high as 80%. There is insufficient data regarding the relationship between 25-hydroxyvitamin D [25(OH) D] levels and outcomes in medical intensive care unit (MICU). The goal of this study was to evaluate the prevalence of 25(OH) D deficiency in MICU and its relationship with outcomes. SUBJECTS AND METHODS: This was a retrospective study in a MICU of a teaching medical college hospital of Eastern India. All patients admitted to MICU, who had levels of 25(OH) D available, were included in the study. The discriminative powers of admission and lowest 25(OH) D values regarding day-30 mortality were evaluated by producing receiver operating curves (ROC). Binary end points were analyzed by means of a Fisher's exact test. Continuous variables were compared by using unpaired t-tests, Welch's tests, or Wilcoxon ranksum tests. All odds ratios and their corresponding 95% confidence intervals were calculated according to the profile-likelihood method. The time from inclusion to death in the two groups was compared with the use of the log-rank test, and the results are presented as Kaplan-Meier curves. Hazard ratios for death from hypo 25(OH) D were calculated by logistic regression model. All P values were 2-tailed and P < 0.05 was considered statistically significant. RESULTS: Of the 300 patients admitted during the study period, 25(OH) D levels were available in 152 patients (50.6%). Of these 152 patients, 15 patients (9.8%) had 25(OH) D insufficiency (20-29.9 ng/dL), 79 (51.9%) had 25(OH) D deficiency (0-19.9 ng/dL), and the levels were normal (>30 ng/dl) in 58 (38.2%) patients. Most of the patients with deficient 25(OH) D levels were females (P < 0.05). Higher mortality (P = 0.01), increased length of MICU stay, and prolonged ventilation were observed in patients with 25(OH) D deficiency. CONCLUSIONS: Patients with 25(OH) D deficiency in MICU have increased hospital mortality, longer mechanical ventilation, and longer MICU stay. PMID- 25125806 TI - Chronic obstructive pulmonary disease and low bone mass: A case-control study. AB - BACKGROUND AND OBJECTIVE: Low bone mass (osteopenia and osteoporosis) is one of the effects associated with chronic obstructive pulmonary disease (COPD). There is very little data from Saudi Arabia on COPD and low bone mass. This retrospective study was done to assess the prevalence of osteoporosis and osteopenia in COPD patients attending King Fahd Hospital of the University (KFHU), Alkhobar. PATIENTS AND METHODS: After obtaining the ethical approval from the research committee, all patients seen between at the King Fahd Hospital of the University between January 2010 and December 2012 were included. The inclusion criteria included a follow up of a minimum 2 years, and the Medical Records should have the details of forced expiratory volume in one second (FEV1), blood bone profile and bone biomarkers and dual-energy X-ray absorptiometry (DEXA) scan. Patients were labeled as osteopenia if the T score was -<1 to <-2.5 and osteoporosis of <-2.5 as per the WHO definition of osteopenia and osteoporosis. RESULTS: Seventy-three patients were being followed in the clinics and 49 patients satisfied the inclusion criteria. The average age was 60.6 +/- 10.47 years; males were 43 and females 6. Three (6.1%) were normal and the remaining 46 (93.9%) were with low bone mass. Thirty-two (65.3%) were osteoporotic and 14 (28.57%) were osteopenic. The average duration of COPD was 4.5 +/- 6.2 years. Majority (n = 36, 73.4%) of patients were in the Global Initiative for COPD (GOLD) class II and III. FEV1 was significantly lower in the patients with low bone mass 1.66 +/- 0.60 versus 3.61 +/- 0.58 (P < 0.001). CONCLUSIONS: Our study shows that over 90% of Saudi Arabian patients with COPD suffer from osteopenia and osteoporosis and unfortunately they remain under diagnosed and undertreated. PMID- 25125808 TI - Primary mediastinal large B-cell lymphoma: Clinical features, prognostic factors and survival with RCHOP in Arab patients in the PET scan era. AB - OBJECTIVE: PMBCL is a distinct type of nonhodgkins lymphoma with specific clinicopathological features. To clarify clinical features, treatment alternatives and outcomes, we evaluated 28 Arab patients treated with chemotherapy or radiotherapy between 2006 and 2011. PATIENTS AND METHODS: PMBCL lymphoma patients identified according to WHO classification and treated at KCCC between 2006 and 2011 were included in this study. Demographic and clinical data are presented as means or medians. Overall survival was estimated using the Kaplan-Meier method. Survival rates were compared using the log-rank test. A P < 0.05 was considered significant. RESULTS: The median age of the patients was 31 years and the male to female ratio was 2:1. Majority of the patients (75%) presented with stage I/II disease. Most had features of local extension like pleural effusion (18%) and SVCO (39%). Only 11% of the patients had bone marrow involvement at presentation. 96% of the patients required biopsy from the mediastinal mass either by image guided core biopsy (75%) or by surgical biopsy. Most patients were treated by RCHOP and involved field radiotherapy. Patients with positive PET scan after RCHOP chemotherapy received salvage chemotherapy and BEAM autologous marrow transplant. The five year OS for the entire group was 85% while the PFS was 73%. Patients who had PET scan for response evaluation had better OS [P = 0.013] and PFS [P = 0.039] when compared with those patients who received only radiotherapy based on CT scan evaluation. CONCLUSION: PMBCL is a specific lymphoma entity seen in the young with good survival. The role of PET scan for response evaluation and the type of consolidation therapy needs to be further clarified. PMID- 25125807 TI - Prevalence and correlates of osteoporosis in chronic obstructive pulmonary disease patients in India. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a syndrome of progressive airflow limitation caused by the abnormal inflammatory reaction of the airway and lung parenchyma. Osteoporosis is one of the major extrapulmonary manifestations of COPD. The, prevalence of osteoporosis in COPD patients in Indian population is unknown. OBJECTIVES: To study the prevalence of osteoporosis in COPD and to define various risk factors associated with reduced bone mineral density (BMD) in COPD. MATERIALS AND METHODS: The study was done in the department of Pulmonary Medicine of a tertiary care hospital. All the diagnosed cases of COPD according to the Global Initiative for Obstructive Lung Disease (GOLD) guidelines were included in this study. The present study was a prospective study in for a period of 1 year. A brief history of the patients was taken, especially regarding duration of illness, number of exacerbations in the past 3 years, smoking in pack years, and history of steroid use (both systemic and inhaled steroids) after which cumulative dose of steroids was calculated. Spirometry was done in all these patients to stage the severity of COPD according to GOLD criteria. DEXA scan of the lumbar spine was done using bone densitometer to determine osteoporosis. A world Health Organization (WHO) criterion for definition of osteoporosis was applied and patients with T-score of > -2.5 standard deviation (SD) were diagnosed to have osteoporosis, -1 SD to -2.5 SD were diagnosed to have osteopenia and < -1 SD as normal. Statistical analysis for association of COPD with osteoporosis was done using chi-square test. Risk factors for osteoporosis were identified by univariate and multivariate logistic regression analysis. RESULTS: A total of 102 COPD patients were included in the study. Among these, 68 patients (66.6%) had osteoporosis and 20 patients (19.6%) had osteopenia. Majority (64.7%) of the patients who had osteoporosis had stage III and stage IV COPD disease. It was observed that as the severity grade of COPD increased, the risk of osteoporosis also increased. The bone mineral density (BMD) showed a significant difference among different stages of COPD. As the severity of the stage of COPD increased, BMD decreased. It was also observed that patients with lower body mass index (BMI) had higher prevalence of osteoporosis (37.3%) as compared to overweight patients. On univariate analysis, it was observed that risk factors for osteoporosis were female sex, higher number of exacerbations, BMI, and severity of COPD. After using multivariate logistic regression analysis, stage IV COPD (odds ratio (OR): 34.48, 95% confidence interval (CI): 1.59-1,000, P < 0.02), number of acute exacerbations >3 (OR: 30.3, 95% CI: 4.74-200, P < 0.01), and steroid cumulative dose >1,000 mg (OR: 7.35, 95% CI: 0.92-58.5, P < 0.04) were observed to be significant risk factors for osteoporosis in COPD patients. CONCLUSIONS: In the present study, the prevalence of osteoporosis was 66.6% and another 19.6% had osteopenia. As the severity of COPD increased, the risk of osteoporosis increased. GOLD stage III and stage IV patient had significantly lower BMD as compared to stage I and stage II of COPD disease. Stage IV COPD disease, use of oral or parenteral glucocorticoids, and repeated number of exacerbations were found to be independent risk factors for osteoporosis in COPD patients. Thus, high clinical suspicion and early diagnosis and treatment is required in the evaluation of osteoporosis in COPD patients so that the quality of life can be improved in these patients. PMID- 25125809 TI - A questionnaire-based study on the role of environmental factors in allergic bronchopulmonary aspergillosis. AB - BACKGROUND AND AIMS: Allergic bronchopulmonary aspergillosis (ABPA) is an immunological disorder caused by hypersensitivity against Aspergillus fumigatus. The pathogenesis of ABPA remains unknown. Few studies have investigated the role of environmental factors in pathogenesis of ABPA. Herein, we investigate the role of environmental factors in ABPA. MATERIALS AND METHODS: In this prospective case control study, consecutive patients with asthma (Aspergillus sensitized and unsensitized) and ABPA were investigated using a standardized questionnaire to enquire into their demographic characteristics, clinical details, exposure to organic matter and living conditions (home environment, presence of moisture in the walls, and others). Asthma severity and control was assessed using the 2002 The Global Initiative for Asthma (GINA) recommendations and asthma control test, respectively. RESULTS: During the study period, 202 subjects of asthma (103 and 99 Aspergillus unsensitized and sensitized asthma, respectively) and 101 ABPA with a mean (SD) age of 35.3 (14.7) years were included. The baseline characteristics were similar in the two groups except for a higher prevalence of severe persistent asthma in the ABPA group (79% vs. 44%, P = 0.0001). No significant differences in environmental factors were noted in the ABPA population compared to asthmatic patients except for a higher rural residence in ABPA (47% vs. 66%, P = 0.007). CONCLUSIONS: The study found no significant environmental differences in ABPA compared to asthmatic patients. It is likely that environmental factors are not the primary pathogenetic factors in causation of ABPA. PMID- 25125811 TI - Effect of type II diabetes mellitus on treatment outcomes of tuberculosis. AB - CONTEXT: There is conflicting evidence of effect of diabetes on treatment of tuberculosis (TB). There is a need to investigate effect of diabetes on outcomes of TB treatment under field conditions in India. AIMS: To compare treatment outcomes among TB patients with diabetes with those without diabetes. SETTING AND DESIGN: Study was conducted in Cuddalore, Tamil Nadu, among patients registered with Revised National TB Control Programme. Prospective observational study design was used. MATERIALS AND METHODS: Registered TB patients aged 30 and above were invited to participate in the study. Those who were not aware of their diabetic status were diagnosed using oral glucose tolerance test. A total of 89 diabetic and 120 non-diabetic patients were recruited in the study. They were followed up till the end of treatment and outcomes were recorded. STATISTICAL ANALYSIS USED: Treatment outcomes in the two groups were compared using bi variate and multi-variate analysis. RESULTS: Bi-variate (unadjusted) analysis showed similar treatment success rates in the two groups. But, the adjusted odds ratios for successful treatment among diabetic patients were significantly lower (0.191, 95% CI 0.04-0.90) for pulmonary TB patients and for smear positive pulmonary TB patients (odds ration 0.099, 0.013-0.761). Diabetes was found to be predictor for sputum positivity at end of treatment. CONCLUSIONS: Diabetes increases risk of poor treatment outcomes among pulmonary TB patients. The study highlights need of screening of TB patients for diabetes. There is need to see the effect of glycemic control on treatment outcomes among diabetics. PMID- 25125810 TI - Prevalence of water pipe smoking in the city of Mashhad (North East of Iran) and its effect on respiratory symptoms and pulmonary function tests. AB - BACKGROUND: The prevalence of water pipe (WP) smoking was studied using a standard questionnaire. Pulmonary function tests were also compared between WP smokers and non-smokers. MATERIALS AND METHODS: The prevalence of WP smoking was studied using a standard questionnaire. Pulmonary function tests including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximal mid expiratory flow (MMEF), peak expiratory flow (PEF), maximal expiratory flow at 75%, 50%, and 25% of the FVC (MEF75,50,25) were compared between WP smokers and non-smokers. RESULTS: A total of 673 individuals including 372 males and 301 females were interviewed. The number of WP smokers was 58 (8.6%) including 24 males (6.5%) and 34 females (11.3%). All pulmonary functional test (PFT) values in WP smokers were lower as compared to the non-smokers (P < 0.05 to P < 0.001). The prevalence and severity of respiratory symptoms (RS) in WP smokers were higher than non-smokers (P < 0.05 to P < 0.001). There were negative correlations between PFT values and positive correlation between RS and duration, rate, as well as total smoking (duration X rate) (P < 0.05 to P < 0.001). CONCLUSION: In this study the prevalence of WP smoking in Mashhad city was evaluated for the first time. The results also showed a significant effect of WP smoking on PFT values and respiratory symptoms. PMID- 25125812 TI - Usage patterns of biomarkers in non-small-cell lung cancer patients in India: Findings from a systematic review and survey. AB - INTRODUCTION: Personalized medicine has facilitated improved management of non small cell lung cancer (NSCLC) patients by identifying predictive and prognostic biomarkers for enhanced efficiency of detection and efficacy of treatment. This systematic review and survey assessed the patterns of biomarker usage, molecular testing techniques to diagnose patients with NSCLC in India and testing techniques recommended by cancer societies. MATERIALS AND METHODS: Studies were retrieved from Embase, PubMed, and Cochrane databases for the last 12 years, using relevant search strategies as per the Cochrane methodology for systematic reviews. Outcomes of interest were biomarkers for NSCLC, patterns of biomarker testing, diagnostic methods, guidelines and cost of biomarker testing. RESULTS: In all, 499 studies were identified for screening and 17 primary publications were included in the review. Epidermal growth factor receptor (EGFR) expression and epithelial markers (particularly cytokeratins (CK)) were the most commonly reported biomarkers (7/17) and immunohistochemical (IHC) staining was the most common technique for detection of biomarkers. The frequency of EGFR mutations was higher among women than men. Significantly elevated levels of CK-18 were observed in patients with squamous cell carcinoma and of CK-19 in patients with adenocarcinoma, squamous cell carcinoma, and NSCLC (P < 0.001). Prognostic or predictive role of cytokines and angiogenic markers as well as DNA expression were evaluated. The survey also showed that IHC was the most common technique for detection of biomarkers. CONCLUSIONS: This systematic review and survey provides valuable information on biomarker usage in the Indian population, and highlights the need for initiatives required for future biomarker testing in India. PMID- 25125813 TI - Incidental detection of a tumour on 68-Gallium DOTANOC PET/CT. PMID- 25125814 TI - Hydatid cyst of lung: An uncommon cause of chest pain in young. AB - Echinococcosis can involve any organ. The liver is the most common organ involved, followed by the lungs. Depending on the location of involvement it can have varied presentation. We describe a young adult presenting with chest pain secondary to a pulmonary giant hydatid cyst. A pulmonary hydatid cyst should be considered in the differential diagnosis of patients presenting with chest pain without conventional risk factors of coronary artery disease, especially in a tropical region. PMID- 25125815 TI - Anaplastic thyroid carcinoma presenting as bilateral pleural effusion. AB - Anaplastic thyroid cancer presenting as bilateral malignant pleural effusion is rarely reported. We present a case who presented solely with respiratory symptoms and subsequently found to be having bilateral malignant pleural effusion secondary to anaplastic thyroid cancer. PMID- 25125816 TI - Single-stage management of large pulmonary and hepatic hydatid cysts in pediatric age group: Report of two cases. AB - Two patients presented to us with very similar clinical and radiological presentation of huge hydatid cysts in the lung and liver. The first patient was an 11-year-old female child and the second one was a 9-year-old male child. The clinical features in both were breathlessness on exertion, pain abdomen, and abdominal distension. Chest Roentgenogram along with computed tomogram of the chest and abdomen revealed presence of thin-walled homogenous large cysts, one in the right lung and two in the liver, in both the cases. Although the liver cysts were of larger size and occupying most of the right lobe of the liver and part of the left lobe, liver function tests were normal. All three cysts were enucleated in the same sitting by a combined thoracic and abdominal approach (thoracotomy followed by laparotomy). After enucleation of the cyst, capitonnage of the cavity in the lung was done and the liver cavities were filled with omentum to prevent collection of fluid and abscess formation. Both patients recovered well, although the second patient required abdominal drain for a long period of 1 month for bile leakage which decreased gradually and eventually stopped. PMID- 25125817 TI - Secondary pleural hydatidosis: Complication of intrapulmonary echinococcosis. AB - Hydatid disease has a wide geographic distribution around the world. In human, the liver is the most commonly affected organ, followed by the lungs. Intrathoracic extrapulmonary locations are generally the mediastinum, pleura, pericardium and chest wall. Pleural involvement usually follows the rupture of a pulmonary or hepatic cyst inside the pleural space causing secondary pleural hydatidosis. We report four cases of patients who were referred to our hospital for management of pleural hydatid disease as a complication of intrapulmonary echinococcosis. PMID- 25125818 TI - Bronchial mucous gland adenoma presenting as massive hemoptysis: A diagnostic dilemma. AB - Mucous gland adenoma of the lung is an uncommon benign tumor that histologically resembles the mucus-secreting component of tracheobronchial gland. The majority arises within the main, lobar, or segmental bronchi but parenchymal involvement had also been reported. We herein present a case of mucous gland adenoma arising from the left lower lobe bronchus. The 32-year-old female presented with massive hemoptysis, productive cough, and dyspnoea and was clinically misdiagnosed as tuberculosis. Radiology proved to be inconclusive. This case highlights the importance of a complete lung work up in patients presenting with signs of respiratory tract infections. PMID- 25125819 TI - Primary synovial sarcoma of lung. AB - A synovial sarcoma (SS) is a rare form of cancer which usually occurs near the joints of the arm, neck, or leg, but has been documented in most human tissues and organs, including the brain, prostate, and heart. Primary pulmonary SS is an extremely rare tumor. We report a case of primary SS of lung who presented with severe chest pain and a large right lung mass with right-sided pleural effusion in computed tomography (CT) scan of thorax. The diagnosis was made on the basis of CT-guided core biopsy and immunohistochemistry. On immunohistochemistry, tumor cell expressed epithelial membrane antigen, bcl 2, Vimentin and smooth muscle actin and were immunonegative for S100 and cytokeratin. So, the final diagnosis was primary SS. PMID- 25125820 TI - Is femoral uptake of Tc99m-methylene diphosphonate on bone scintigraphy in bronchogenic carcinoma an alarming sign: A case report and brief review of literature? AB - Detection of skeletal metastasis in patients with lung cancer is important from management point of view. We report the bone scan finding in a patient with non small cell lung carcinoma showing isolated abnormal tracer in femur and having a characteristic appearance in computed tomography, highlighting the importance of bone scan in patients with bronchogenic carcinoma. PMID- 25125821 TI - Pulmonary alveolar proteinosis due to mycophenolate and cyclosporine combination therapy in a renal transplant recipient. AB - Pulmonary alveolar proteinosis (PAP) is an orphan disease characterized by the accumulation of excess of surfactant within alveoli and bronchioles. The primary form of PAP (P-PAP; also referred to as idiopathic or autoimmune) is the most common form. It is mediated through a circulating neutralizing antibody against granulocyte-macrophage colony-stimulating factor. Secondary PAP (S-PAP) can be induced by a host of inciting agents and is far more liable to progress to terminal respiratory failure. We describe a rare case of S-PAP occurring in a renal transplant recipient due to mycophenolate and cyclosporine combination therapy, which resolved spontaneously following withdrawal of these drugs. PMID- 25125822 TI - Miliary nodules: An unusual presentation of allergic bronchopulmonary aspergillosis. AB - Allergic bronchopulmonary aspergillosis (ABPA) is an immune-mediated inflammatory disease caused by hypersensitivity to Aspergillus fumigatus. A wide spectrum of plain radiographic appearances has been described in ABPA, though none are pathognomonic of ABPA. The common radiological abnormalities encountered are fleeting pulmonary opacities, bronchiectasis, and mucoid impaction. Uncommon radiological findings encountered in ABPA include pulmonary masses, perihilar opacities simulating hilar adenopathy, and pleural effusions. However, miliary nodules as a radiological presentation of ABPA are very rare and only one case has been reported in literature. It is often misdiagnosed and mismanaged as tuberculosis; thus, the clinician should be vigilant enough to diagnose this very rare entity. PMID- 25125823 TI - Community acquired Roseomonas infection in a pre-existing Tubercular lung lesion. AB - Roseomonas are nonfermenting opportunistic Gram-negative bacilli belonging to the newly established genus of Roseomonas. The clinical experience with the species is limited and is difficult to diagnose because of limited expertise and lack of commercially available identification kits with any of the automated systems. This is a first ever reported case of secondary bacterial infection due to Roseomonas genomospecies 6 in a patient of pulmonary tuberculosis from the Indian subcontinent. PMID- 25125824 TI - A 55 years old man with pulmonary alveolar microlithiasis. AB - Pulmonary alveolar microlithiasis (PAM) is a very rare diffuse chronic lung disease characterized by deposition of small spherules of calcium phosphate within the alveolar cavity. The disease is usually seen from birth up to 40 years of age and is usually diagnosed incidentally during radiography of the chest for other reasons. Most of patients are asymptomatic or having very mild symptoms and the majority of patients either have normal or restrictive pulmonary function test. Clinically, the course of the disease is different; it remains static in few patients or it may progress to pulmonary fibrosis, respiratory failure and cor pulmonale in others. In this case report, we present a 55-year-old man who presented with moderate shortness of breath which has progressed from mild symptoms with in the previous years. His chest high-resolution CT scan showed diffusely scattered, ill-defined little shadowy micronodules which involve the left lung; lingula and left lower lobe in particular. A lung biopsy confirmed the diagnosis of PAM. He was followed up for 1 year with treatment by steroid and alendronate, and no progression was noticed in fact improvement in pulmonary function test noticed. This is the first case report of PAM in Kurdistan. PMID- 25125826 TI - Vitamin D status in critical care: Contributor or marker of poor health? PMID- 25125825 TI - An unusual cause of recurrent pneumonia in adults. AB - Selective IgM deficiency is a rare primary immunodeficiency defined as isolated low levels of IgM. It presents with recurrent infections and has been described as first presenting in adulthood with recurrent respiratory tract infections. Unlike its better known counterpart of IgA deficiency, this particular immunodeficiency is often overlooked. We present a case of selective IgM deficiency who presented with recurrent respiratory infections. PMID- 25125827 TI - Usher's syndrome: Can primarily be a primary ciliary disorder? PMID- 25125828 TI - Congenital lobar emphysema presenting at late childhood: A rare case report. PMID- 25125829 TI - Remarkable computed tomography findings in Boerhaave's syndrome. PMID- 25125830 TI - Long-term doxycycline and lung function in chronic obstructive pulmonary disease: A pilot observation. PMID- 25125831 TI - Spontaneous resolution of pulmonary inflammatory pseudotumor. PMID- 25125832 TI - Mucormycosis masquerading as an endobronchial tumor. PMID- 25125833 TI - Extensive unilateral tuberculosis lung with segmental atresia of principal bronchus. PMID- 25125834 TI - Subclinical airflow obstruction in allergic rhinitis. PMID- 25125835 TI - A letter in response to recurrent subcutaneous emphysema in a treated tuberculosis patient: Is there any association? PMID- 25125836 TI - Planning in case control studies: A comment on the relationship between lung function and indoor air pollution among rural women in the Niger Delta region of Nigeria. PMID- 25125837 TI - Comments on pathogenesis of acquired tracheobronchoesophageal fistula following blunt chest trauma. PMID- 25125838 TI - Authors' reply. PMID- 25125839 TI - CRIS Guidelines (Checklist for Reporting In-vitro Studies): A concept note on the need for standardized guidelines for improving quality and transparency in reporting in-vitro studies in experimental dental research. AB - In vitro studies form a pivotal role in dental research contribution to a substantial evidence base. The reporting standards of these studies are not uniform thus resulting in lacunae in evidence reported. The effort of this concept note is to propose a Checklist for Reporting in vitro Studies (CRIS guidelines) that would promote quality and transparency in reporting in vitro studies. PMID- 25125841 TI - C-shaped root canal configuration: A review of literature. AB - The aim is to review and discuss the etiology, incidence, anatomic features, classification, diagnosis and management of the C-shaped canal configuration. C shaped canal configuration is a variation that has a racial predilection and is commonly seen in mandibular second molars. The intricacies present in this variation of canal morphology can pose a challenge to the clinician during negotiation, debridement and obturation. Manual and electronic searches of literature were performed from 1979 to 2012, in Pub Med by crossing the keywords: C-shaped canals, mandibular second molar, mandibular first premolar, root canal morphology. Knowledge of the C-shaped canal configuration is essential to achieve success in endodontic therapy. Radiographic and clinical diagnoses can aid in identification and negotiation of the fan-shaped areas and intricacies of the C shaped anatomy. Effective management of this anomalous canal configuration can be achieved with rotary and hand instrumentation assisted with sonics and ultrasonics. Modifications in the obturation techniques will ensure a 3 dimensional fill of the canal system and chamber retained restorations like amalgam or composites, serve as satisfactory post endodontic restorations. PMID- 25125840 TI - Validity of bond strength tests: A critical review: Part I. AB - Adhesive systems are selected based on their bond strengths achieved while testing in laboratories. These bond strengths can predict the longevity of a restoration to some extent. There were several discrepancies in the reported bond strengths. To critically review the reliability of macro-bond strength tests used to evaluate resin-tooth interface. Relevant literature published between January 1983 and May 2013 was collected from PubMed database, Google scholar, and hand searched journals of Conservative Dentistry, Endodontics and Dental materials. Variables that influence the test outcome are categorized into substrate-related factors, factors related to specimen properties, preparation of specimens, and test methodology. Impact of these variables on the test outcome is critically analyzed. There is lack of a standard format for reporting the bond strength tests, which could lead to misinterpretation of the data and bonding abilities of adhesives. PMID- 25125843 TI - Effects of sports beverages and polishing systems on color stability of different resin composites. AB - BACKGROUND: Consumption of certain acidic beverages may alter the physical and esthetic properties of resin composites. AIM: The aim of this study was to evaluate the effects of two sports beverages on color stability of two different types of resin composites polished with different composite polishing systems. MATERIALS AND METHODS: A total of 96 disk-shaped specimens (diameter: 8-mm and thickness: 2-mm) were made from two different resin composites (Cavex Quadrant Universal-LC, and Clearfil-APX). All of the specimens were stored in distilled water for 24 h at 37 degrees C. Color measurements of each specimen were performed using a colorimeter according to the CIEL*a*b* color scale at baseline and after seven days of immersion in two different sports beverages (Powerade and Buzzer). STATISTICAL ANALYSIS USED: The data were evaluated using Kruskal Wallis and Mann-Whitney U tests. RESULTS: Significant differences were found between the mean DeltaE values of the groups after seven days of immersion (P < 0.05). The highest level of the mean color change was observed in the Clearfil APX specimens immersed in Powerade (DeltaE = 3.5 +/- 0.9). Control groups stored in distilled water for both composites exhibited small color changes (DeltaE-Cavex-bur = 2.1 +/- 1; DeltaE-Clearfil APX-bur = 2.1 +/- 0.4). CONCLUSION: Sport beverages caused discoloration in the resin composites after seven days. PMID- 25125842 TI - Comparison of shear bond strength of composite resin to enamel surface with laser etching versus acid etching: An in vitro evaluation. AB - INTRODUCTION: The aim of the study is in vitro evaluation of the shear bond strength of composite resin bonded to enamel which is pretreated using acid etchant and Er,Cr:Ysgg. MATERIALS AND METHODS: 40 extracted human teeth were divided in two groups of 20 each (Groups A and B). In Group A, prepared surface of enamel was etched using 37% phosphoric acid (Scotchbond, 3M). In Group B, enamel was surface treated by a an Er, Cr: YSGG laser system (Waterlase MD, Biolase Technology Inc., San Clemente, CA, USA) operating at a wavelength of 2,780 nm and having a pulse duration of 140-200 microsecond with a repetition rate of 20 Hz and 40 Hz. Bonding agent ((Scotchbond Multipurpose, 3M) was applied over the test areas on 20 samples of Groups A and B each, and light cured. Composite resin (Ceram X duo Nanoceramic restorative, Densply) was applied onto the test areas as a 3 * 3 mm diameter bid, and light cured. The samples were tested for shear bond strength. RESULTS: Mean shear bond strength for acid-etched enamel (26.41 +/- 0.66MPa, range 25.155 to 27.150 MPa) was significantly higher (P < 0.01) than for laser-etched enamel (16.23 +/- 0.71MPa, range 15.233 to 17.334 MPa). CONCLUSIONS: For enamel surface, mean shear bond strength of bonded composite obtained after laser etching were significantly lower than those obtained after acid etching. PMID- 25125844 TI - Evaluation of smear layer removal from ultrasonically prepared retrocavities by three agents. AB - OBJECTIVES: To evaluate the efficacy of 35% orthophosphoric acid, 24% ethylenediaminetetraacetic acid (EDTA) and 10% citric acid in the removal of smear layer from retrocavities prepared with ultrasonic retro-tips using scanning electron microscopy. MATERIALS AND METHODS: Root canals of fifty single-rooted teeth were cleaned, shaped, and obturated with gutta-percha and AH plus sealer. The apical 3 mm of each root was sectioned with a diamond disc and retrograde cavities were prepared with Kis # 1 ultrasonic retro-tips to a depth of 3 mm. Retro cavities in Group I were treated with a gel of 35% orthophosphoric acid for 15 seconds, Group II were treated with a gel of 24% EDTA at neutral pH for 2 minutes, and Group III were treated with a gel of 10% citric acid for 2 minutes, followed by 1 minute rinsing with distilled water for all groups. The samples were prepared for scanning electron microscopic observation. Scoring was performed for the presence of the smear layer on the walls of the retrocavity. RESULTS: In the orthophosphoric acid group, it was observed that all dentinal tubules were open in 70% of the samples. The majority of analyzed samples in EDTA and citric acid group showed dentinal tubules covered with the smear layer. CONCLUSIONS: Application of 35% orthophosphoric acid gel for 15 seconds on retrocavities prepared with ultrasonic retro-tips is the most effective means for removal of smear layer. PMID- 25125845 TI - Comparative evaluation of antimicrobial efficacy of triple antibiotic paste and calcium hydroxide using chitosan as carrier against Candida albicans and Enterococcus faecalis: An in vitro study. AB - AIM: To analyze the sustained release of intracanal medicaments with or without a carrier and testing their antimicrobial efficacy in root canal against Candida albicans and Enterococcus faecalis. MATERIALS AND METHODS: A total of 80 single rooted anterior teeth were selected, root canal preparation was done, and teeth were divided into two halves and contaminated with C. albicans and E. faecalis, which were further divided into four test groups each according to intracanal medicaments used. Chitosan was used as vehicle for triple antibiotic paste (TAP) and calcium hydroxide and antimicrobial assessment was performed on second and seventh day. Dentine samples were collected after each. RESULTS: All four medicaments used in this study showed antifungal and antibacterial activity. Group II (TAP + chitosan) and Group III (Ca(OH)2 + chitosan) had the higher antifungal and antibacterial activity compared with two other groups. CONCLUSION: Combination of TAP + chitosan and Ca(OH)2 + chitosan produced better results compared with the combination of medicaments with saline. PMID- 25125846 TI - "Evaluation of sealing ability of MM-MTA, Endosequence, and biodentine as furcation repair materials: UV spectrophotometric analysis". AB - AIM: To evaluate the sealing ability of MICRO-MEGA Mineral Trioxide Aggregate, Endosequence, Biodentine as furcation repair materials using a dye extraction leakage method. MATERIALS AND METHODS: Forty mandibular molars were randomly divided according to the material used for perforation repair. Group I- (left unsealed) control, Group II-MICRO-MEGA Mineral Trioxide Aggregate, Group III - Endosequence, Group IV - Biodentine. All samples were subjected to orthograde and retrograde methylene blue dye challenge followed by dye extraction with 65% nitric acid. Samples were then analyzed using Ultra violet (UV) Visible Spectrophotometer. RESULTS: Biodentine showed highest dye absorbance, whereas Endosequence showed lowest dye absorbance when compared with other repair materials. CONCLUSION: Within the limitations of this study, it was observed that Endosequence showed better sealing ability when compared with other root repair materials. PMID- 25125847 TI - Comparative evaluation of microleakage in Class II restorations using open vs. closed centripetal build-up techniques with different lining materials. AB - BACKGROUND: Evaluation of microleakage is important for assessing the success of new restorative materials and methods. AIM AND OBJECTIVES: Comparative evaluation of microleakage in Class II restorations using open vs. closed centripetal build up techniques with different lining materials. MATERIALS AND METHODS: Standardized mesi-occlusal (MO) and distoocclusal (DO) Class II tooth preparations were preparedon 53 molars and samples were randomly divided into six experimental groups and one control group for restorations. Group 1: Open Sandwich technique (OST) with flowable composite at the gingival seat. Group 2: OST with resin-modified glass ionomer cement (RMGIC) at the gingival seat. Group 3: Closed-Sandwich technique (CST) with flowable composite at the pulpal floor and axial wall. Group 4: CST with RMGIC at the pulpal floor and axial wall. Group 5: OST with flowable composite at the pulpal floor, axial wall, and gingival seat. Group 6: OST with RMGIC at the pulpal floor, axial wall, and gingival seat. Group 7: Control - no lining material, centripetal technique only. After restorations and thermocycling, apices were sealed and samples were immersed in 0.5% basic fuchsin dye. Sectioning was followed by stereomicroscopic evaluation. RESULTS: Results were analyzed using Post Hoc Bonferroni test (statistics is not a form of tabulation). Cervical scores of control were more than the exprimental groups (P < 0.05). Less microleakage was observed in CST than OST in all experimental groups (P < 0.05). However, insignificant differences were observed among occlusal scores of different groups (P > 0.05). CONCLUSION: Class II composite restorations with centripetal build-up alone or when placed with CST reduces the cervical microleakage when compared to OST. PMID- 25125848 TI - Effects of two bioactive materials on survival and osteoblastic differentiation of human mesenchymal stem cells. AB - OBJECTIVES: Activation of mineralization process in periradicular tissues following the injuries, is important in repair mechanisms. The objective of this study was to investigate the effects of CEM cement on survival and mineralization of human mesenchymal stem cells (hMSCs) and compare it with MTA. MATERIALS AND METHODS: hMSCs that were planted on test material extracts and culture media were the experimental and control groups, respectively. The cytotoxicity of these materials was investigated using Methyl thiazol tetrazolium assay. After 7 days, alizarin red staining, alkaline phosphatase (ALP) assays, and qRT-PCR were used to assess the mineralization, expression of ALP, and gene expression (collagen type 1 and osteocalcin), respectively. The results were evaluated by ANOVA analysis and multiple comparisons test. P < 0.05 was considered as statistically significant. RESULTS: Cell viability was not significantly different. Alizarin red and alkaline phosphatase staining showed mineralization in all three groups. In qRT-PCR, the expression of collagen type 1 is not significantly different among the three groups. Osteocalcin gene expression was significantly higher in the CEM group compared to the control (P < 0.05). CONCLUSION: CEM cement has acceptable toxicity and could induce mineralization process and enhance osteocalcin gene expression which is associated with mineralization in hMSCs. PMID- 25125849 TI - Evaluation of fracture resistance of roots obturated with resilon and thermoplasticized gutta-percha: An in vitro study. AB - AIM: To investigate and compare the fracture resistance of resilon and realseal filled root canals with those that were obturated with thermoplasticized gutta percha and AH-plus endodontic sealer. MATERIALS AND METHODS: Eighty extracted human mandibular single-rooted premolars stored in 10% formalin were used in this study. They were prepared by using a crown-down technique, debrided and irrigated with NaOCl, EDTA, and normal saline and divided into four groups. Group I = Negative control, canals prepared but no obturation was done; Group II = Positive control obturated with dual cure composite resin; Group III = Obturated with thermoplasticized GP and AH-plus; Group IV = Obturated with resilon and realseal. All root specimens were stored for two weeks in 100% humidity to allow for complete setting of the sealer. Each specimen was mounted in acrylic in a polyvinyl ring and tested for fracture resistance with a universal testing machine. The loading fixture of the machine was mounted with its spherical tip aligned with the center of the access opening of each root. A vertical loading force was applied until it fractured the root. The force values were subjected to statistical analysis: Kruskall-Wallis H-test and Mann-Whitney U-test. RESULTS: Group comparison revealed that Group II (positive control) had significantly higher values of resistance to fracture as compared to all the other groups. While Group IV (resilon with realseal) had significantly higher values of resistance to fracture as compared to Group I (negative control). CONCLUSION: On the basis of our findings, it can be concluded that filling the root canals with resilon and realseal increased the in vitro resistance to fracture of single canal extracted teeth. resilon and realseal demonstrated high fracture-resistance values and could be an alternative to the conventional gutta-percha. PMID- 25125850 TI - Root canal configuration of permanent maxillary first molar in Khasi population of Meghalaya: An in vitro study. AB - AIMS AND OBJECTIVE: To investigate the root canal configuration of permanent maxillary first molar in Khasi population of Meghalaya. MATERIAL AND METHODS: Sixty (60) permanent maxillary first molars collected from patients of Khasi population of Meghalaya were studied using canal staining and clearing technique. Observations of the number of roots, root canal configuration, lateral canal, apical delta, and presence of the additional type of canals were made. RESULTS: Based on Vertucci's classification the different types of canal identified are: Mesiobuccal root, Type I (28.3%), Type II (28.3%), Type IV (30.0%), Type V (5.0%), Type VI (6.7%), and an additional type of canal (2-1-2-1-2; 1.7%) were observed. The distobuccal root displayed Type I (95%), Type II (1.7%), Type V (3.3%). The most prevalent canal configuration in the palatal roots is Type I (98.3%), Type II (1.7%). CONCLUSION: In Khasi population of Meghalaya, the most prevalent root canal configuration in the mesiobuccal root is Type IV followed by Type I and Type II. MB2 canals are present in more than 65% cases. In palatal and distobuccal roots, Type I configuration is present in most cases. Racial divergence may be responsible for such variations. PMID- 25125851 TI - Comparative evaluation of a novel smart-seal obturating system and its homogeneity of using cone beam computed tomography: In vitro simulated lateral canal study. AB - AIM: The aim was to evaluate and compare a novel polyamide polymer based obturating system and Gutta-percha and sealer in filling simulated lateral canals and their homogeneity when used for obturating the root canals. MATERIALS AND METHODS: A total of 60 freshly extracted human single rooted teeth with fully formed apices were selected for this study. Teeth were de-coronated, and roots were standardized to a working length of 15 mm. Root canal preparation was carried out with rotary Protaper file system in all groups. The specimens were then randomly divided into three groups A, B, and C (n = 20). Ten samples from each group were decalcified and simulated lateral canals were made at 2, 4, and 6 mm from the root apex. Remaining ten samples from each group were maintained calcified. Group A was obturated with SmartSeal system (Prosmart-DRFP Ltd., Stamford, UK). Group B was obturated with sectional backfill method. Group C was obutrated with cold lateral compaction method (control). Decalcified samples from the respective groups were analyzed with digital radiography and photography and the measurement of the linear extension and area of lateral canal filling was done using UTHSCSA (UTHSCSA Image Tool for Windows version 3.0, San Antonio, TX, USA) software. Calcified samples were subjected to cone beam computed tomography image analysis sectioned axially. RESULTS: Group A 92.46 +/- 19.45 showed greatest extent of filling in lateral canals and denser homogeneity of oburation, followed by Group B 78.43 +/- 26.45 and Group C 52.12 +/- 36.67. CONCLUSIONS: Polyamide polymer obturation proved to have greater efficiency when compared with Gutta-percha system, when used for obturation with regards to adaptation of the sealer and penetration into the simulated lateral canals. PMID- 25125852 TI - Comparison of surface abrasion produced on the enamel surface by a standard dentifrice using three different toothbrush bristle designs: A profilometric in vitro study. AB - AIM: The aim was to assess, in vitro, the effect on surface abrasivity of enamel surface caused by three different types (flat trim, zig-zag, bi-level) of toothbrush bristle design. MATERIALS AND METHODS: Twenty-four freshly extracted, sound, human incisor teeth were collected for this study. The enamel slab was prepared, which were mounted, on separate acrylic bases followed by subjected to profilometric analysis. The surface roughness was measured using the profilometer. The specimen were divided into three groups, each group containing eight mounted specimens, wherein, Group 1 specimens were brushed with flat trim toothbrush; Group 2 brushed with zig-zag and Group 3 with bi-level bristle design. A commercially available dentifrice was used throughout the study. A single specimen was brushed for 2 times daily for 2 min period for 1 week using a customized brushing apparatus. The pre- and post-roughness value change were analyzed and recorded. STATISTICAL TEST: Kruskal-Wallis test and Mann-Whitney U test. RESULT: The results showed that surface abrasion was produced on each specimen, in all the three groups, which were subjected to brushing cycle. However, the bi-level bristle design (350% increase in roughness, P = 0.021) and zig-zag bristle design (160% increase in roughness, P = 0.050) showed significantly higher surface abrasion when compared with flat trim bristle design toothbrush. CONCLUSION: Flat trim toothbrush bristle produces least surface abrasion and is relatively safe for use. PMID- 25125853 TI - Comparison of the cleaning efficacy of EndoVac with conventional irrigation needles in debris removal from root canal. An in-vivo study. AB - AIM AND OBJECTIVE: The aims were to evaluate the root canal debris removal after irrigation with EndoVac system and to compare its efficacy with Max-i-Probe needles. MATERIALS AND METHODS: Fifteen matched pairs of single canalled vital teeth with mature apices indicated for extraction were selected. After working length determination and biomechanical preparation, the teeth in the right quadrant were irrigated with EndoVac system and with Max-i-Probe needles in the left quadrant using 3% NaOCl and 17% ethylenediaminetetraacetic acid. Teeth were extracted and marked at 1 and 3 mm from working length and decalcified in Kristenson's solution. Stained histologic slides were observed under trinocular research microscope. Wilcoxon signed-rank test was used for statistical analysis. The statistical significance was set at P < 0.05 and the analysis was performed using SPSS version 11.0 software. RESULTS: No statistical significant difference was found at 3 mm level between the groups. Group I had significantly less debris at 1 mm level. CONCLUSION: EndoVac performed better in removing debris from the apical thirds of root canals. PMID- 25125854 TI - Five root canals in peg lateral incisor with dens invaginatus: A case report with new nomenclature for the five canals. AB - This case report describes endodontic treatment completed in a peg-shaped maxillary lateral incisor, with single root and five root canals of which, one is due to dens invaginatus. Cone beam computed tomogram scanning confirmed the unique morphology of the tooth. New nomenclature for the five canals is proposed. PMID- 25125855 TI - Type II canal configuration and Type I Dens invaginatus. AB - The prevalent notion about maxillary central incisor with normal external morphology is a tooth with single root and root canal. A case in which all four maxillary incisors were having Type II canal configurations (Vertucci's classification) is reported, in addition, the lateral incisors revealed dens invaginatus with a Type I pattern as suggested by Ohler's classification and a large periapical lesion was seen in relation to the right lateral incisor. The diagnosis was confirmed with the aid of spiral computed tomography (CT) and canals obturated. Nonsurgical healing of the lesion was assessed by reviewing the case at prefixed intervals of time. PMID- 25125856 TI - Cone beam computed tomography evaluation and endodontic management of permanent mandibular second molar with four roots: A rare case report and literature review. AB - The morphological variation in the number of roots and root canals, especially in multi-rooted teeth is a constant challenge for diagnosis and successful endodontic therapy. Knowledge of the most common anatomic characteristics and their possible variations is fundamental. Although, endodontic management of four rooted mandibular first molars have been observed on a few occasions in the literature, to the best of our knowledge four-rooted mandibular second molars having two mesial and two distal roots have not been reported. This paper highlights endodontic management of mandibular second molar with four roots (two mesial and two distal) with one canal in each root and its cone beam computed tomography (CBCT) evaluation which was primarily done for post treatment assessment for diagnosing post-endodontic complications, at the same time confirmed our radiographic diagnosis of this variation. This also helped us portraying the anatomy of this rare variation. PMID- 25125857 TI - Use of quartz fiber post for reattachment of complex crown root fractures: A 4 year follow-up. AB - Dental hard tissue trauma is among the most common cases encountered in dental practice. Simple tooth fractures, which occur due to sharp blows, are widely seen in all age groups, especially in young adults. If in case of complex fractures the fractured tooth fragments are available to the dentist in a clean and hydrated state, reattachment of the tooth fragment is the most conservative and biological treatment option possible. Cases of enamel and dentin fractures not involving pulp are treated by reattaching the fragment with adhesives and composite resin. However, fractures involving the pulp require reinforcement by quartz fiber posts and resin luting cement. In cases of fractures extending subgingivally, an envelope flap helps to achieve the desired isolation and visibility. This article presents 2 case reports of reattachment of fractured tooth fragments. The first case showing a 4-year success was treated without raising a flap. The second case with a subgingival fracture was treated by raising a flap. Reattachment is the most economical, biologically acceptable and esthetic restorative option for dental trauma. PMID- 25125859 TI - Repair of incomplete horizontal mid-root fracture of maxillary central incisor with mineral trioxide aggregate: A follow up report. AB - Incomplete horizontal fractures occur in teeth with developing root as it cannot withstand traumatic force during injury. Diagnosis and management of such cases are difficult. Cone Beam Computed Tomography (CBCT) served as efficient diagnostic tool and follow up measure and the use of Mineral Trioxide Aggregate in treatment had shown a better prognostic importance. In present case, treatment outcome of one year is reported in incompletely fractured mid-root of central incisor and the clinical approach is discussed. PMID- 25125862 TI - Time for change: integrating palliative medicine to mainstream medicine. PMID- 25125860 TI - CBCT diagnosis and endodontic management of a maxillary first molar with unusual anatomy of two palatal canals: A case report. AB - It is crucial for any clinician to have a thorough knowledge about the normal anatomy of tooth and always be vigilant for any variations to ensure endodontic success. An anatomic variant like additional canals in the palatal root of maxillary molar is not commonly reported. This clinical case report presents the application of cone beam computed tomography as a useful imaging technique in endodontics for the management of teeth with aberrant anatomy. Here, maxillary first molar having two canals in the palatal root, two canals in mesiobuccal root and one canal in distobuccal root was managed successfully using cone beam computed tomography scan as a diagnostic aid. PMID- 25125863 TI - End-of-Life Care for Patients Afflicted with Incurable Malignancy and End-Stage Renal Disease. PMID- 25125864 TI - Preference of the place of death among people of pune. AB - AIM: Provision of end-of-life care requires that we have adequate information about the preferred place of death in the population. Since no such study is reported in India, this study was taken up in and around Pune, a large cosmopolitan city. SETTING AND DESIGN: A questionnaire was designed in three parts and distributed among the people above the age of 18 in and around Pune. MATERIALS AND METHODS: The questionnaire had three parts the first being a consent form, followed by one for collection of personal information and lastly questions specific to the subject matter. Filled forms were screened for inconsistencies, gaps of information and errors. RESULTS: The population survey was mixed, both urban and rural, men and women, educated and uneducated, young and old. Despite this heterogeneity, the results were consistent to the point that most of the people surveyed preferred home as the place of death. This preference cuts across all barriers, the only difference being that women had a stronger preference for home death compared to men. CONCLUSIONS: Helping people to die at their preferred place is a part of end-of-life care. Majority of people surveyed by us, prefer to die at home, where they are relatively more comfortable. Public and governmental policies should be directed toward facilitating home deaths. PMID- 25125865 TI - Poor health related quality of life among patients of sickle cell disease. AB - BACKGROUND: Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and vascular occlusion, causing recurrent painful episodes, neuro cognitive deficits, organ failures and death in early adulthood. Besides the medical consequences, most of the families with a child of SCD have to cope with financial and social crisis. Quality of life (QOL) is a broad multidimensional concept that usually includes subjective evaluations of both positive and negative aspects of life. Other than health; emotional well being, social dysfunction, chronic pain and fatigability are also important aspects of overall quality of life that add to the complexity of its measurement. AIM: The present case control study was designed to determine the health related quality of life (HRQoL) in patients of sickle cell disease and to compare it with patients of other chronic non-communicable diseases. SETTING AND DESIGN: Case control study conducted at tertiary health care facility of Central India. MATERIAL AND METHODS: The present study conducted to measure HRQoL among patients of SCD and patients of other chronic non-communicable diseases. A translated and pretested version of WHO SF-36 questionnaire was used to measure HRQoL. RESULTS: We observed that there was significantly lower HRQoL among SCD patients. CONCLUSION: Besides merely pharmacotherapy, restoration of overall quality of life should be the mainstay of management of patients with SCD. PMID- 25125866 TI - Palliative approach in advanced pelvic osteosarcoma: a single centre experience of a rare disease. AB - BACKGROUND: Pelvic osteosarcoma is a rare and aggressive malignant neoplasm with poor outcomes. It represents only 5% of all osteosarcomas. The authors present our institute's experience in management and outcomes of five successive patients of pelvic osteosarcoma. MATERIALS AND METHODS: We retrospectively reviewed five patients of pelvis osteosarcoma treated in our institute from September 2008 to December 2010. Clinical characteristics and treatment (CCT) modality in form of surgery and chemotherapy were noted. Statistical analysis was done with regards to progression-free survival (PFS) using Kaplan-Meier survival analysis. RESULTS: The median age of the patients was 16.0 years. The median duration of symptoms was 9 months. One patient had lung metastases at presentation. All patients received systemic chemotherapy. One patient underwent surgery in the form of limb sparing approach. Three patients had partial response to treatment, one had complete response, and one had progressive disease. Median duration of PFS was 7 months only. CONCLUSIONS: Pelvic osteosarcomas are rare neoplasms with aggressive growth patterns. Survival results are poor in view of advanced stage of presentation and difficult surgical approaches. The combined modality approach is needed to improve the results. PMID- 25125867 TI - Quality of life in cancer patients undergoing chemotherapy in a tertiary care center in malwa region of punjab. AB - OBJECTIVE: The objective of this prospective, non-interventional, 4-month observational study was to analyze and compare patient-reported quality of life (QOL) and their physical/psychosocial symptom burden during their respective chemotherapy sessions. MATERIALS AND METHODS: A prospective and descriptive study was carried out jointly by Pharmacology and Oncology Departments of a tertiary care center in Malwa region of Punjab. The data collection was performed by administering validated questionnaire/response after taking informed consent. RESULTS: A total of 131 cancer patients were recruited with the mean age of 49.05 +/- 14.35 (SD (standard deviation)) years. As per the QOL scoring of Global Health Status (GHS) and four items of symptom scale, that is, insomnia, pain, appetite loss, and constipation, and financial difficulties attained a significance difference. GHS significantly improved in group three as compared to group one, indicating that the patient's overall health/QOL improved as the chemotherapy session progressed. CONCLUSION: Although QOL scoring system did not show significant improvement in all areas (except insomnia, pain, appetite loss, constipation, and financial difficulties) with reference to their respective chemotherapy cycles, but a judicious diagnosis with an appropriate treatment including chemotherapy may lessen the negative perception of cancer as a deadly and fatal disease in our rural population. PMID- 25125868 TI - Adaptation of a quality of life questionnaire for Iranian patients with esophageal cancer. AB - INTRODUCTION: Evaluation of quality of life is very important in cancer patients. Esophagus-specific quality of life questionnaire (QLQ-OES18) is a disease specific questionnaire for assessing quality of life in esophageal cancer (EC). So we aimed to translate and evaluate the reliability and validity of the QLQ OES18 when applied to Iranian patients. MATERIALS AND METHODS: This study was designed as cross-sectional study on 62 newly confirmed EC in two referral hospital in Tehran, Iran. Reliability of the subscales was evaluated by intraclass correlation coefficients. Pearson's correlations of an item with its own scale and other scales were calculated to assess convergent and discriminant validity. Clinical validity was also evaluated by known-group comparisons. RESULTS: Cronbach's alpha was higher than 0.7 in most subscales. All subscales met the standards of convergent and discriminant validity. Also QLQ-OES18 had discriminatory power for differentiation between patient's groups with different clinical status. CONCLUSION: Our results provide evidences that Persian version of QLQ-OES18 is a valid and reliable questionnaire when applied to a sample of Iranian patients with EC and is recommended for use in clinical research. PMID- 25125869 TI - Fear of Cancer Recurrence and its Predictive Factors among Iranian Cancer Patients. AB - CONTEXT: Fear of cancer recurrence (FOCR) is one of the most important psychological problems among cancer patients. In extensive review of related literature there were no articles on FOCR among Iranian cancer patients. AIM: The aim of present study was to investigation FOCR and its predictive factors among Iranian cancer patients. MATERIALS AND METHODS: In this descriptive-correlational study 129 cancer patients participated. For data collection, the demographic checklist and short form of fear of progression questionnaire was used. Logistic regression was used to determine predictive factors of FOCR. RESULT: Mean score of FOCR among participants was 44.8 and about 50% of them had high level of FOCR. The most important worries of participants were about their family and the future of their children and their lesser worries were about the physical symptoms and fear of physical damage because of cancer treatments. Also, women, breast cancer patient, and patients with lower level of education have more FOCR. DISCUSSION: There is immediate need for supportive care program designed for Iranian cancer patients aimed at decreasing their FOCR. Especially, breast cancer patients and the patient with low educational level need more attention. PMID- 25125870 TI - Does pain behavior influence assessment of pain severity? AB - CONTEXT: Nurses are involved in assessment of pain in most clinical settings. Pain continues to be underestimated and undertreated. MATERIALS AND METHODS: This study assessed the rating of pain severity by nurses who observed the two case scenarios using role plays. The data were computed and frequency distribution was derived. RESULTS: Majority of the nurses underrated the pain and based their ratings on various factors. CONCLUSIONS: It is important to increase the awareness among nurses about comprehensive assessment of pain for better management. PMID- 25125871 TI - Palliative care for patients with malignancy and end-stage renal failure on peritoneal dialysis. AB - BACKGROUND: Many patients on peritoneal dialysis experience a poor quality of life because of a high burden of comorbid conditions. Dialysists must pay more attention to reducing a patient's pain and suffering, both physical and psychological and improve the quality of life for the patients as much as possible. A consensus regarding eligibility for palliative care and the delivery of these inventions does not currently exist. OBJECTIVE: The present study aimed to describe the implementation of palliative care for end-stage renal failure patients on peritoneal dialysis. DESIGN: A report on three cases. MATERIALS AND METHODS: This study included three outpatients on peritoneal dialysis who received palliative care and died between January 2008 and June 2010. MEASUREMENTS: The patients' comorbidities, nutritional status, and functional status were evaluated using the Charlson comorbidity score, subjective global assessment, and Karnofsky Performance Score index, respectively. The Hamilton depression and Hamilton anxiety scales were also employed. The patients' clinical manifestations and treatments were reviewed. RESULTS: Each patient displayed 11 16 symptoms. The Charlson comorbidity scores were from 11 to 13, the subjective global assessment indicated that two patients were class assigned to "C" and one to class "B", and the mean Karnofsky index was <40. Among these patients, all experienced depression and two experienced anxiety, Low doses of hypertonic glucose solutions, skin care, psychological services, and tranquillizers were intermittently used to alleviate symptoms, after making the decision to terminate dialysis. The patients died 5 days to 2 months after dialysis withdrawal. CONCLUSION: The considerable burden associated with comorbid conditions, malnutrition, poor functional status, and serious psychological problems are predictors of poor patient prognoses. Withdrawal of dialysis, palliative care, and psychological interventions can reduce patient distress and improve the quality of life before death, with the care provided. PMID- 25125872 TI - The multidisciplinary team in palliative care: a case reflection. AB - This essay is a reflection on the multidisciplinary team in palliative care, from the perspective of a final year MBBS student from the UK spending one month with an Indian pain and palliative care team at Institute Rotary Cancer Hospital (IRCH), AIIMS, New Delhi. PMID- 25125873 TI - Role of a dentist in comprehensive management of a comatose patient with post traumatic head injury and neuropathological chewing. AB - Injury of the head and neck region can result in substantial morbidity. Comprehensive management of such patients requires team work of several specialties, including dentists. A young female patient with extensive loss of cranium and associated pathological chewing was referred to the dental department. The lost cranium was replaced by a custom-made, hand-fabricated cranioplast. Trauma due to pathological mastication was reduced by usage of a custom-made mouthguard. Favorable results were seen in the appearance of the patient and after insertion of the mouthguard as evidenced in good healing response. The intricate role of a dental specialist in the team to manage a patient with post traumatic head injury has been highlighted. The take away message is to make the surgical fraternity aware of the scope of dentistry in the comprehensive management of patients requiring special care. PMID- 25125874 TI - Management of total cancer pain: a case of young adult. AB - Pain due to cancer is one of the most distressing symptoms experienced by the patients at some or the other time during the course of treatment or disease progression. The multidimensional nature of cancer pain is characterized by various dimensions including physical, social, psychological, and spiritual; which together constitute the term "total pain". Young cancer patients illustrate their unique psychological and developmental needs. This case report highlights the concept of "total cancer pain" in a young adult and demonstrates his distinctive social, spiritual, and psychological sufferings. The report emphasizes that addressing all these concerns is considerably significant in order to provide optimal pain relief to the patient. In the present scenario, it has been done by a skillful multiprofessional team communicating effectively with both the patient and the carer. PMID- 25125875 TI - Primary peritoneal serous carcinoma: a rare case and palliative approach. AB - Primary peritoneal serous carcinoma (PPSC) is a rare primary malignancy that diffusely involves the peritoneum, indistinguishable clinically and histopathologically from primary serous ovarian carcinoma. The origin of PPSC has not been well characterized. Here we present a case of PPSC diagnosed in ultrasonography-guided fine needle aspiration cytology (FNAC) in a 76- old female presenting with ascites, abdominal pain, distension and constipation. PPSC is an unusual tumour but cytomorphology is distinctive enough to diagnose preoperatively. In the case report hereby described PPSC is an inoperable malignancy, hence chemotherapy and palliative care are the only offered treatment. PMID- 25125876 TI - Use of Opioids and Sedatives at End-of-Life. AB - Despite their proven efficacy and safety, opioid and sedative use for palliation in patients afflicted with cancer in Singapore have been shown to be a fraction of that in other countries. This paper explores the various psychosocial and system-related factors that appear to propagate this conservative approach to care in what is largely a western-influenced care practice. A search for publications relating to sedative and opioid usage in Asia was performed on PubMed, Google, Google Scholar, World Health Organization, and Singapore's government agency websites using search terms such as "opioids," "sedatives," "palliation," "end-of-life-care," "pain management," "palliative care," "cancer pain," "Asia," "Singapore," and "morphine." Findings were classified into three broad groups - system-related, physician-related, and patient-related factors. A cautious medico-legal climate, shortage of physicians trained in palliative care, and lack of instruments for symptom assessment of patients at the end of life contribute to system-related barriers. Physician-related barriers include delayed access to palliative care due to late referrals, knowledge deficits in non palliative medicine physicians, and sub-optimal care provided by palliative physicians. Patients' under-reporting of symptoms and fear of addiction, tolerance, and side effects of opioids and sedatives may lead to conservative opioid use in palliative care as well. System-related, physician-related, and patient-related factors play crucial roles in steering the management of palliative patients. Addressing and increasing the awareness of these factors may help ensure patients receive adequate relief and control of distressing symptoms. PMID- 25125877 TI - Nicotine replacement therapy for palliation of nicotine abstinence syndrome- is it worth? PMID- 25125878 TI - Polyherbal formulation: Concept of ayurveda. AB - Ayurveda is one of the traditional medicinal systems of Indian. The philosophy behind Ayurveda is preventing unnecessary suffering and living a long healthy life. Ayurveda involves the use of natural elements to eliminate the root cause of the disease by restoring balance, at the same time create a healthy life-style to prevent the recurrence of imbalance. Herbal medicines have existed world-wide with long recorded history and they were used in ancient Chinese, Greek, Egyptian and Indian medicine for various therapies purposes. World Health Organization estimated that 80% of the word's inhabitants still rely mainly on traditional medicines for their health care. The subcontinent of India is well-known to be one of the major biodiversity centers with about 45,000 plant species. In India, about 15,000 medicinal plants have been recorded, in which the communities used 7,000-7,500 plants for curing different diseases. In Ayurveda, single or multiple herbs (polyherbal) are used for the treatment. The Ayurvedic literature Sarangdhar Samhita' highlighted the concept of polyherbalism to achieve greater therapeutic efficacy. The active phytochemical constituents of individual plants are insufficient to achieve the desirable therapeutic effects. When combining the multiple herbs in a particular ratio, it will give a better therapeutic effect and reduce the toxicity. This review mainly focuses on important of the polyherbalism and its clinical significance. PMID- 25125879 TI - Role of complementary and alternative medicine in geriatric care: A mini review. AB - Since time immemorial homo sapiens are subjected to both health and diseases states and seek treatment for succor and assuagement in compromised health states. Since last two decades the progressive rise in the alternative form of treatment cannot be ignored and population seems to be dissatisfied with the conventional treatment modalities and therefore, resort to other forms of treatment, mainly complementary and alternative medicine (CAM). The use of CAM is predominantly more popular in older adults and therefore, numerous research studies and clinical trials have been carried out to investigate the effectiveness of CAM in the management of both communicable and non-communicable disease. In this current mini review, we attempt to encompass the use of CAM in chronic non-communicable diseases that are most likely seen in geriatrics. The current review focuses not only on the reassurance of good health practices, emphasizing on the holistic development and strengthening the body's defense mechanisms, but also attempts to construct a pattern of self-care and patient empowerment in geriatrics. The issues of safety with CAM use cannot be sidelined and consultation with a health care professional is always advocated to the patient. Likewise, responsibility of the health care professional is to inform the patient about the safety and efficacy issues. In order to substantiate the efficacy and safety of CAMs, evidence-based studies and practices with consolidated standards should be planned and executed. PMID- 25125880 TI - Intensification of bioactive compounds extraction from medicinal plants using ultrasonic irradiation. AB - Extraction processes are largely used in many chemical, biotechnological and pharmaceutical industries for recovery of bioactive compounds from medicinal plants. To replace the conventional extraction techniques, new techniques as high pressure extraction processes that use environment friendly solvents have been developed. However, these techniques, sometimes, are associated with low extraction rate. The ultrasound can be effectively used to improve the extraction rate by the increasing the mass transfer and possible rupture of cell wall due the formation of microcavities leading to higher product yields with reduced processing time and solvent consumption. This review presents a brief survey about the mechanism and aspects that affecting the ultrasound assisted extraction focusing on the use of ultrasound irradiation for high-pressure extraction processes intensification. PMID- 25125881 TI - Psidium guajava: A review on its potential as an adjunct in treating periodontal disease. AB - Plants for thousands of years have been used to enhance health and for medicinal purposes. Psidium guajava is one which has an enormous wealth of medicinal value. It for long has been known for its anti-inflammatory, antimicrobial, antioxidant, antidiarrheal, antimutagenic properties. Despite of its widespread biologic uses there is a dearth of information on its therapeutic effect in the treatment of periodontal disease. Hence, this review is an attempt to highlight the potential of P. guajava in the treatment of periodontal disease. Internet databases PubMed, Google Scholar were searched and the most relevant articles were considered for review. PMID- 25125882 TI - Rubus fruticosus (blackberry) use as an herbal medicine. AB - Wild grown European blackberry Rubus fruticosus) plants are widespread in different parts of northern countries and have been extensively used in herbal medicine. The result show that European blackberry plants are used for herbal medicinal purpose such as antimicrobial, anticancer, antidysentery, antidiabetic, antidiarrheal, and also good antioxidant. Blackberry plant (R. fruticosus) contains tannins, gallic acid, villosin, and iron; fruit contains vitamin C, niacin (nicotinic acid), pectin, sugars, and anthocyanins and also contains of berries albumin, citric acid, malic acid, and pectin. Some selected physicochemical characteristics such as berry weight, protein, pH, total acidity, soluble solid, reducing sugar, vitamin C, total antioxidant capacity, antimicrobial screening of fruit, leaves, root, and stem of R. fruticosus, and total anthocyanins of four preselected wild grown European blackberry (R. fruticosus) fruits are investigated. Significant differences on most of the chemical content detect among the medicinal use. The highest protein content (2%), the genotypes with the antioxidant activity of standard butylated hydroxyanisole (BHA) studies 85.07%. Different cultivars grown in same location consistently show differences in antioxidant capacity. PMID- 25125883 TI - Molecule mechanism of stem cells in Arabidopsis thaliana. AB - Plants possess the ability to continually produce new tissues and organs throughout their life. Unlike animals, plants are exposed to extreme variations in environmental conditions over the course of their lives. The vitality of plants is so powerful that they can survive several hundreds of years or even more making it an amazing miracle that comes from plant stem cells. The stem cells continue to divide to renew themselves and provide cells for the formation of leaves, stems, and flowers. Stem cells are not only quiescent but also immortal, pluripotent and homeostatic. Stem cells are the magic cells that repair tissues and regenerate organs. During the past decade, scholars around the world have paid more and more attention toward plant stem cells. At present, the major challenge is in relating molecule action mechanism to root apical meristem, shoot apical meristem and vascular system. The coordination between stem cells maintenance and differentiation is critical for normal plant growth and development. Elements such as phytohormones, transcription factors and some other known or unknown genes cooperate to balance this process. In this review, Arabidopsis thaliana as a pioneer system, we highlight recent developments in molecule modulating, illustrating how plant stem cells generate new mechanistic insights into the regulation of plants growth and development. PMID- 25125884 TI - Modulation of diabetes-mellitus-induced male reproductive dysfunctions in experimental animal models with medicinal plants. AB - Today diabetes mellitus has emerged as a major healthcare problem throughout the world. It has recently broken the age barrier and has been diagnosed in younger people also. Sustained hyperglycemia is associated with many complications including male reproductive dysfunctions and infertility. Numerous medicinal plants have been used for the management of the diabetes mellitus in various traditional system of medicine and in folklore worldwide as they are a rich source of bioactive phytoconstituents, which lower blood glucose level and/or also act as antioxidants resulting in the amelioration of oxidative-stress induced diabetic complications. The present review describes the ameliorative effects of medicinal plants or their products, especially on male reproductive dysfunctions, in experimental diabetic animal models. PMID- 25125886 TI - Value addition in sesame: A perspective on bioactive components for enhancing utility and profitability. AB - Sesame seed is a reservoir of nutritional components with numerous beneficial effects along with health promotion in humans. The bioactive components present in the seed include vital minerals, vitamins, phytosterols, polyunsaturated fatty acids, tocopherols and unique class of lignans such as sesamin and sesamolin. The presence of phenylpropanoid compounds namely lignans along with tocopherols and phytosterols provide defense mechanism against reactive oxygen species and increases keeping quality of oil by preventing oxidative rancidity. In this article, we have reviewed the nutraceutical, pharmacological, traditional and industrial value of sesame seeds with respect to bioactive components that hold high antioxidant value. Valuable information on superior functional components of sesame will strongly promote the use of sesame seeds in the daily diet world wide. In spite of huge repertoire of sesame germplasm collection, limited research efforts on the use of conventional and biotechnological methodologies have resulted in minimal success in developing nutritionally superior cultivars. In consequence, value addition efforts in sesame would enable development of genotypes with high antioxidant activity and subsequently prevention of free radical related diseases. Modification of bioactive components in sesame would enable production of stabilized sesame oil with enhanced shelf life and better market value. PMID- 25125887 TI - Pharmacological aspects of Nerium indicum Mill: A comprehensive review. AB - Phytomedicine is the oldest medical practice known to man. Since the dawn of mankind, various plant resources are used to cure different diseases and also for a long and healthy life. The ancient knowledge of plant based medicine has transferred from generations to generations and accumulated as ethnopharmacological knowledge among different ethnic groups. India is the spanning bed of traditional phytomedicinal system where Ayurveda was born out of the knowledge of traditional medicine. In various other countries of South Eastern Asia, South America, and in Arabian countries, still today, a great number of people rely primarily on phytomedicines to cure diseases. In the complementary and alternative medicinal systems, Nerium indicum is one such plant which is famed for its therapeutic efficiency in different diseases globally. In the present time, when the pharmaceutical companies are concentrating more toward the plant based traditional medicines to avoid the side-effects and resistance against synthetic drugs, N. indicum has proved its efficiency in different disease models. Therefore, this review comprehensively covers the medicinal and pharmacological activities of different parts of the plant N. indicum. PMID- 25125888 TI - Comparative evaluation of naftopidil and tamsulosin in the treatment of patients with lower urinary tract symptoms with benign prostatic hyperplasia. AB - INTRODUCTION: Naftopidil, approved initially in Japan, is an alpha1d-adrenergic receptor antagonist (alpha1-blocker) used to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). It is different from tamsulosin hydrochloride and silodosin, in that it has a higher affinity for the alpha1D adrenergic receptor subtype than for the alpha1A subtype and has a superior efficacy to a placebo and comparable efficacy to other alpha1-blockers such as tamsulosin. The incidences of ejaculatory disorders and intraoperative floppy iris syndrome induced by naftopidil may also be lower than that for tamsulosin and silodosin, which have a high affinity for the alpha1A-adrenergic receptor subtype. However, it remains unknown if the efficacy and safety of naftopidil in Japanese men is applicable to Indian men having LUTS/BPH. MATERIAL AND METHODS: Two groups of 60 patients each, having LUTS due to BPH, were treated with tamsulosin 0.4 mg and Naftopidil 75 mg for three months. Ultrasonography (for prostate size, post-void residual volume), uroflowmetry, and the International Prostate Symptom Score (IPSS) and Quality of Life (QOL) score were recorded at the beginning of the study, and then at one and three months. RESULTS: The prostate size, post-void residual volume, all the uroflowmetry variables, and the IPSS QOL scores showed a statistically significant improvement (P < 0.001) in both the groups. The improvement in the average flow rate and the QOL index was better in the naftopidil group on the intergroup comparison and was statistically significant (P < 0.001). CONCLUSION: Although the QOL life index was significantly better in the naftopidil group, overall both naftopidil and tamsulosin were found to be equally effective in the treatment of LUTS due to BPH. PMID- 25125889 TI - Percutaneous nephrolithotomy in children: A preliminary report. AB - OBJECTIVES: The recurrence of pediatric nephrolithiasis, the morbidity of repeated open surgical treatment as well as our experience in percutaneous nephrolithotomy (PNL) in adult patients, all derived us to shift to PNL for managing renal stones >1.5 cm in pediatric patients. Our aim of this study is to evaluate the safety and efficacy of PNL in pediatric patients. MATERIALS AND METHODS: During the period of the month between May 2011 and April 2013, 38 children (47 renal units) underwent PNL for renal stones 1.5-5 cm in length. Patient demographics, stone characteristics, and clinical outcome were prospectively studied. Data of those who underwent conventional and tubeless PNL were compared. Median follow-up period was 12 months (range: 6-24). RESULTS: The median age at presentation was 8-year (range: 3-12). The operative time ranged from 30 to 120 min (median 90). Overall stone clearance rate was 91.5% after single PNL. The median hospital stay was 3 days. Auxiliary procedures were successful for the remaining 4 patients (nephroscopic clearance in one and shockwave lithotripsy in 3). Tubeless PNL was performed in 17 renal units with a comparable outcome to conventional ones. The perioperative complications were noted in 5/47 (10.6%) of all procedures (Clavien Grade II in 4 and Clavien Grade IIIa in 1) and were managed conservatively. CONCLUSIONS: Percutaneous nephrolithotomy for renal stones in pediatric patients is safe and feasible if performed by a well-experienced endourologist. Tubeless PNL is a better choice for children. PMID- 25125890 TI - Safety of latex urinary catheters for the short time drainage. AB - BACKGROUND: In this study, we attempt to identify the most appropriate catheter (silicone vs. latex) for short-term urinary catheterization. We compared the post operative clinico-pathological complications between latex and silicone for short term catheterization in rabbits with hypospadias. MATERIALS AND METHODS: Forty rabbits were used in our study to compare complications of catheterization. They were divided in two groups. Hypospadias like defect was created by a 1 cm long excision of the ventral urethra. For urethroplasty, we used tubularized incised plate technique. Latex and silicon catheters were used in groups 1 and 2, respectively. Post-operatively, routine laboratory urine test and complications (allergy, infection, bleeding) were compared in groups. RESULTS: A total of 40 rabbits underwent hypospadias repair. Findings showed that there were no significant differences between groups based on urine test indices (P = NS). Urinary tract infection rate was 10% (2 rabbits) in latex and 0% in silicone groups (P = NS). There were no significant differences between groups regarding of cystitis grades between study groups (P = NS). CONCLUSION: It seems that urinary tract catheterization with latex catheters is a safe, feasible, and in expensive procedure for short-term post-operative course in hypospadias surgery in patients without latex hypersensitivity. PMID- 25125891 TI - Stentless laparoscopic pyeloplasty: A single center experience. AB - AIM: To assess the effectiveness of laparoscopic stentless pyeloplasty for congenital ureteropelvic junction obstruction. MATERIALS AND METHODS: This was a prospective comparative study conducted over a period of 5 years. The study included 35 cases of primary ureteropelvic junction obstruction (UPJO) with mean age of 29.5 years, divided in two groups- Group A (stent-less, 18 patients) and Group B (stented, 17 patients). Follow up ranged from one to 4years (mean 2 years). Transperitoneal laparoscopic Anderson- Hyene's pyeloplasty was standard for both the groups. Perioperative and postoperative complications were prospectively collected and analyzed by Statistical Package for Social Sciences (SPSS) 17 version using Pearson chi square test. RESULTS: Both the groups were comparable with respect to preoperative differential renal function (DRF) and time required for maximum activity in minutes (tmax.min). Average post operative DRF was significantly higher than preoperative DRF in both the groups. Average tmax was significantly lower after pyeloplasty than pre operative tmax. Mean operative time, mean duration of urethral catheter, and mean duration of drain removal were comparable in both the groups. However bothersome irritative lower urinary tract symptoms (LUTS) and hematuria were significantly more in group B patients (P < 0.0001 and <0.013 respectively). CONCLUSION: In experienced hands, laparoscopic stentless pyeloplasty is as effective method for treating UPJO as its stented counterpart. It is cost effective, avoids stent-related morbidity, and could be performed without compromising the success rate. However, more randomized studies are needed to evaluate the safety of stentless pyeloplasty. PMID- 25125892 TI - Effects of hydrochlorothiazide on kidney stone therapy with extracorporeal shock wave lithotripsy. AB - OBJECTIVE: The aim of this investigation was to assess the efficacy of hydrochlorothiazide as a hypocalciuric diuretic on stone-free rate of renal pelvic calculi after extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A double-blind, placebo-controlled randomized clinical trial was conducted and 52 patients with renal pelvic calculi (diameter <=2 cm) were enrolled from February 2010 to September 2010. ESWL protocol was performed by 2,500 shocks per session. The patients were randomized into two groups: (1) 26 patients who were given 25 mg hydrochlorothiazide twice daily; and (2) 26 patients who received placebo. The stone-free rate was defined as residual calculus size <=4 mm in controlled ultrasound on 2(nd) week, 1 month and 3 months after ESWL. RESULTS: 19 (78%) of the first group and 9 (42.9%) of the second group were stone-free after one session of ESWL (P = 0.02). 88% of the group 1 and 47.8% of the group 2 were stone-free on 1 month after ESWL (P = 0.003); however, this effect of hydrochlorothiazide was not related to the patients' body mass index, age and gender. The accessory treatment procedures were applied in 24% of the group 1 compared with 19% of the group 2 during 3 months (P = 0.68). All patients in both groups were stone-free on 3 months following lithotripsy. CONCLUSIONS: Hydrochlorothiazide did not impact on the stone-free rate and using accessory procedure within 3 months; however, it decreased duration of stone-free status and number of ESWL sessions. PMID- 25125893 TI - Utility of urine cytology in evaluating hematuria with sonographically suspected bladder lesion in patients older than 50 years. AB - PURPOSE: Investigate the utility of urine cytology (UC) in patients older than 50 years with hematuria and sonographically suspected bladder lesion. PATIENTS AND METHODS: Between April 2010 and June 2012, 152 patients above 50 years suffering from hematuria were included in this study. In all patients, ultrasound revealed a lesion suspected to be bladder cancer. Voided urine specimens were taken from all patients and transported to Pathology laboratory and processed within 1-3 h. All patients have undergone a cystoscopy examination and biopsy was taken from any suspicious lesion. The cytological diagnosis was reported as one of three categories, positive or negative or suspicious for malignancy. RESULTS: One hundred thirty three (87.5%) patients in this study proved to have bladder carcinoma in histopathological examination. The sensitivity of UC was 53.4% and only five patients were suspicious. Percentage of positive cytology was highest among patients having gross hematuria (51.3%), posterior wall lesions (75%), papillonodular configuration (81.8%), invasive cancer (59.1%) and bilharzial affection (52.5%). CONCLUSION: Hematuria in patients older than 50 years with sonographically suspected bladder lesion mandates cystoscopy and biopsy. UC does not add more significant information in this group of patients. PMID- 25125894 TI - Use of computed tomography scout film and Hounsfield unit of computed tomography scan in predicting the radio-opacity of urinary calculi in plain kidney, ureter and bladder radiographs. AB - OBJECTIVE: The objective of this study is to determine the diagnostic utility of computed tomography (CT)- scout film with an optimal non-contrast helical CT scan Hounsfield unit (HU) in predicting the appearance of urinary calculus in the plain kidneys, ureter, urinary bladder (KUB)-radiograph. METHODS: A prospective cross-sectional study was executed and data were collected from June 2007 to June 2012 at a tertiary hospital. The included subjects were diagnosed to have <10mm urolithiasis with non-contrast helical CT scan and KUB X-ray, which were carried out on the same day. Both KUB radiographs and CT-scout film were read by two qualified radiologists with inter-observer standardization prior to the study. Urolithiasis characteristics such as stone location, CT attenuation value, CT scout film and KUB radiograph appearance were recorded independently by two observers. Univariate logistic analysis with receiver operating characteristic curve was generated to determine the best cut-off HU value of urolithiases not identified in CT-scout film, but determined radio-opaque in KUB X-ray. Subsequently, its sensitivity, specificity, predictive values and likelihood ratios were calculated. Statistical significance was set at P value of 0.05 or less. RESULTS: Two hundred and three valid cases were included. 73 out of 75 CT scout film detected urolithiasis were identified on plain radiograph and determined as radio-opaque. The determined best cut off value of HU utilized for prediction of radiographic characteristics was 630HU at which urinary calculi were not seen at CT-scout film and were KUB X-ray radio-opaque. The set HU cut off was established of ideal accuracy with an overall sensitivity of 82.2%, specificity of 96.9% and a positive predictive value of 96.5% and negative predictive value of 83.5%. CONCLUSION: Urolithiases identified on the CT-scout film were also seen as radiopaque on the KUB radiograph while those stones not visible on the CT-scout film, but above the optimal HU cut-off value of 630 are also likely to be radiopaque. PMID- 25125885 TI - Cytotoxicity of dietary flavonoids on different human cancer types. AB - Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver) reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment. PMID- 25125895 TI - The expression of vascular endothelial growth factor-C correlates with lymphatic microvessel density and lymph node metastasis in prostate carcinoma: An immunohistochemical study. AB - AIM: To evaluate the expression of two different lymphatic vascular density (LVD) markers (D2-40 and LYVE-1) and a lymphangiogenic cytokine (Vascular Endothelial Growth Factor-C, [VEGF-C]) in prostate carcinoma and to investigate their relationship with the lymph node status. SETTINGS AND DESIGN: Archival material study of 92 non-consecutive radical prostatectomy specimens. MATERIALS AND METHODS: The mean LVD was assessed immunohistochemically in 24 prostate carcinoma specimens from patients with clinically localized disease, who were found to have nodal metastasis (pN1), and was compared with 68 pN0 cases. Furthermore, the mean LVD, VEGF-C expression, and lymphatic invasion were examined in relation to lymph node involvement. RESULTS: Peritumoral (but not intratumoral) mean LVD assessed by D2-40 was higher in pN1 tumors (P = 0.015). LYVE-1 expression was limited and not associated with lymph node status. The VEGF-C expression was higher in the N1 cases and also correlated with the increased mean LVD in both the peri- and intratumoral compartments. Lymphatic invasion was strongly associated with nodal metastasis and higher VEGF-C expression. CONCLUSIONS: Our results indicate that increased peritumoral (but not intratumoral) LVD in the tumor specimen is associated with lymph node metastasis. Increased expression of VEGF-C is associated with higher LVD (in both intratumoral and peritumoral compartments) and with positive lymph node status, indicating a possible dual role in both lymphangiogenesis and lymphatic vessel invasion. PMID- 25125896 TI - Primary Diffuse large B-Cell lymphoma of testis: A single centre experience and review of literature. AB - BACKGROUND: Primary testicular lymphoma constitutes 1-2% of Non-Hodgkin's lymphomas affecting elderly men >60 years of age. Most often it is a Diffuse large B cell lymphoma (DLBCL) and treatment involves multimodality approach involving surgery, chemotherapy and radiotherapy. Outcome remains poor in spite of aggressive therapy. MATERIALS AND METHODS: We retrospectively reviewed 286 registered cases of DLBCL (aged >14 years) from 2007 to 2011 and found nine primary testicular involvement patients. These cases were analyzed for baseline clinical features, investigations, staging, treatment and outcome. RESULTS: Median age was 58 (46-76) years. All patients presented with testicular swelling, two had the presence of B symptoms, and three with abdominal lymphadenopathy. Six had stage IE disease and three patients had stage IIE. All patients underwent orchiectomy. Eight patients received combination chemotherapy and six completed three or more cycles. Four achieved complete response, among these three relapsed after 32, 42, 70 months and one was lost to follow up. Two had a progressive disease, among these one died of disease and one alive with disease. Complete follow up was available from five patients and median survival was 36 months (11 78 months). CONCLUSION: Primary testicular DLBCL is uncommon, needs multimodality treatment and central nervous system prophylaxis to improve the survival. The outcome needs to be further investigated using biological approaches (Rituximab based) and/or more aggressive management. PMID- 25125897 TI - Long-term outcome of transobturator suburethral tape procedure for treatment of female stress urinary incontinence. AB - OBJECTIVE: The aim is to evaluate the long-term safety and efficacy of transobturator tape (TOT) procedure in the treatment of women with stress urinary incontinence (SUI) by subjective and objective measures. PATIENTS AND METHODS: A total 48 women with SUI underwent the TOT procedure during the period from December 2005 to February 2008. The follow-up period ranged between 60 and 84 months (mean 71 months). Mean age was 44.21 +/- 7.52 (range: 30-58). Preoperative and early postoperative data were retrieved from the patient's medical files. Follow-up evaluation was carried out every 3 months during the 1(st) year and yearly afterwards by history taking (including incontinence and quality-of-life questionnaire), clinical examination, urine analysis, abdominopelvic ultrasonography, and urodynamic studies when indicated. RESULTS: At 12-month follow-up, the cure, improvement, and failure rates were 39 patients (81.25%), 5 (10.42%) and 4 (8.33%), respectively. The corresponding rates at the last follow up were 38 (79.15%), 5 (10.42%) and 5 (10.42%) respectively. The postvoid residual urine and peak flow rates did not differ significantly between the preoperative values and at the last follow-up. The complication rates after a mean 71-month included one patient with voiding difficulty and two patients with de novo urgency. No case was recorded with retention of urine or erosion. CONCLUSIONS: Transobturator tape procedure appeared to be effective minimally invasive procedure for SUI with low rate of complication and good long-term outcome. PMID- 25125898 TI - Congenital anterior urethrocutaneous fistula: Two case reports and review of literature. AB - Congenital anterior urethrocutaneous fistula (CAUF) of the male urethra is a rare anomaly. CAUF can be defined as a urethral fistula in which the urethra and external urethral meatus are intact, typically with intact prepuce and no history of any penile trauma (including surgical trauma).We report 2 cases of CAUF to highlight this pathology with hints of the published similar cases in the literatures and discuss the surgical reconstruction ways for management. PMID- 25125899 TI - Solitary extramedullary plasmacytoma of the penis. AB - Solitary extramedullary plasmacytomas are rare plasma cell malignancies, particularly outside the upper aerodigestive tract. A 90-year-old male presented with a penile mass suspicious for penile carcinoma. Pathology revealed the tumor to be an Epstein-Barr virus-associated plasmacytoma with no radiographic evidence of bone or other soft tissue involvement. There was no laboratory evidence of multiple myeloma. PMID- 25125900 TI - Simple cyst of urinary bladder. AB - Simple cysts are rare in the urinary bladder and can pose a diagnostic dilemma to both the urologist and the histopathologist. No case study was found in the database of Elsevier Science Direct, Spring-Link, or PubMed. We present two cases of subserous cyst in the bladder and discuss the diagnosis and treatment of the condition. The cystic lesion at bladder dome was detected by radiologic examination and confirmed by cystoscopy. In case 1, transurethral resection was first performed which was followed by partial cystectomy; In case 2, the cyst was removed with the urachus using laparoscopic surgery. The patients recovered uneventfully and the histopathology showed cysts in subserous layer of urinary bladder. The bladder cyst should be distinguished from urachal tumor, and laparoscopic partial cystectomy is the preferred operative procedure. PMID- 25125901 TI - Urinary bladder radiotherapy-related chondroblastic osteosarcoma: Rare case report and review of literature. AB - Radiation-related osteosarcomas are well described malignant mesenchymal neoplasms, yet their pathogenesis is not fully understood. They are generally classified into either skeletal osteosarcomas, or their and rare soft tissue counterpart. The occurrence of osteosarcoma in the urinary bladder (UB) following radiotherapy is exceedingly rare. To the best of our knowledge, only two cases of radiation-related urinary bladder osteosarcoma have been published; we herein describe another case of an 85-year-old man who developed post radiotherapy chondroblastic osteosarcoma of the urinary bladder four years following initial surgical resection and radiotherapy for bladder urothelial carcinoma. We believe that this is the first case of radiation-related chondroblastic osteosarcoma arising in the urinary bladder. In addition, we review the literature and explore the possible histogenesis of this rare neoplasm. PMID- 25125902 TI - Radiation induced sarcoma: Everything comes with a price. PMID- 25125904 TI - Renal cell carcinoma and plasma cell myeloma: Coincidence or true association? PMID- 25125903 TI - Renal cell carcinoma and plasma cell myeloma: Unique association and clinical implications. AB - Several case series, in the recent past, have postulated an association between plasma cell myeloma (MM) and renal cell carcinoma (RCC). Population-based data have revealed a bi-directional association between these two malignancies, which points to shared risk factors, similar cytokine (Interleukin-6, IL-6) requirements for growth and survival, and overlapping clinical presentation. The presence of lytic lesions in a patient with prior RCC may simulate bone metastasis; thus, leading to a diagnostic pitfall with potentially adverse clinical implications. Besides these, therapeutic strategies employed for MM have been tried for RCCs with partial success. We aimed to describe two patients, aged 64 and 54 years, with RCC-MM association, with review of relevant literature; and create awareness among pathologists/hematologists, and oncologists. Elucidating a common genetic basis might throw some light in understanding the pathobiology of these tumors and development of newer targeted therapies. PMID- 25125905 TI - Dermatofibrosarcoma protuberans of penis: Case report and literature review. AB - Dermatofibrosarcoma protuberans (DFSP) is a rare mesenchymal skin tumor with intermediate to low grade malignancy and occasional distant metastasis and high rate of recurrence locally. It mostly involves trunk, extremities, scalp, and neck. This article describes a middle-aged married male with a DFSP lesion involving ventral aspect of glans and distal shaft of penis who underwent local excision and primary closure. The patient was tumor-free at three years of follow up. PMID- 25125906 TI - Rectourethral fistula: A rare complication of injection sclerotherapy. AB - In the modern era, the incidence of rectourethral fistula (RUF) has been on a rise due to an increasing number of surgeries being performed for prostatic carcinoma. Other causes of this condition still remain rare and their management differs from that of post prostatectomy RUF. We report a rare case of a young man who presented with leakage of urine per rectum 4 weeks after injection sclerotherapy for haemorrhoids. A Micturating Cystourethrogram/Retrograde Cystourethrogram revealed the presence of RUF arising at the level of prostrato membranous urethra and the urine examination did not show any fecal contamination of urine. A fistula at the level or verumontanum along with stricture of the distal penile urethra was demonstrated on urethroscopy. The patient was successfully managed by dilatation of the stricture segment and urethral catheterization. RUF can rarely result from injection sclerotherapy and must be thoroughly evaluated. Cases which present early and have minimal contamination of urine by fecal contents can be conservatively managed with a simple Foleys catheterization for 4-6 weeks after ruling out any obstruction distal to the fistulous tract. PMID- 25125907 TI - Recurrent dermatomyositis manifesting as a sign of recurrent transitional cell carcinoma of urinary bladder: Long-term survival. AB - The association between urological malignancies and paraneoplastic syndromes has been well documented. We report a case of recurrent dermatomyositis manifesting as a sign of metastatic recurrence of non-muscle-invasive transitional cell carcinoma of the bladder, a relationship which has only been referred to in a few reports. The case highlights a few important clinical challenges; firstly, the importance of thorough investigation for underlying malignancy in patients with dermatomyositis, as successful treatment of such malignancy can lead to resolution of paraneoplastic symptoms, and secondly, a high index of suspicion of recurrence in cases where paraneoplastic manifestations recur. Metastatic pulmonary recurrence without local evidence of disease at a follow-up of 4 years makes this case unique. Moreover, in the light of our experience and reported literature, a framework is suggested to approach such a diagnostic dilemma in the future. Description of the case will guide clinicians in the future, in case they encounter such an unusual clinical scenario. This could also serve as a hypothesis-generating source for designing future research as well. PMID- 25125908 TI - Renal allograft transplant recipient with ruptured hydatid native kidney. AB - Echinococcosis of the kidneys in a renal transplant recipient is extremely rare and its occurrence being related to immunosuppression is a possibility which needs further characterisation. Ruptured renal hydatid in a renal transplant recipient is not reported so far to our best knowledge. We present a 42-year-old renal allograft receipient who presented one year after transplant with left flank pain, palpable left lumbar mass and gross hydatiduria. Investigations revealed a ruptured native hydatid kidney. Patient was managed with a combination of chemotherapy and left native nephrectomy and discharged in a satisfactory condition. PMID- 25125910 TI - Hemorrhagic cystitis: A rare manifestation of organophosphate poisoning. PMID- 25125909 TI - Atypical isolated urethral tuberculosis associated with inflammatory stenosis and fistulas. PMID- 25125911 TI - Estimation of age from development and eruption of teeth. AB - The developing dentition is used to assess maturity and estimate the age in many disciplines including anthropology, archeology, forensic science, pediatric dentistry and orthodontics. There is evidence that dental development is less effected than skeletal development by malnutrition and hormonal disorders. There are two methods of dental age assessment, radiographically and by clinically visualization of eruption of teeth. The clinical method to assess dental age is based on the emergence of teeth in the mouth. This method is more suitable since it does not require any special equipment, expertise and is more economical. Tooth formation is the best choice for estimating the age as variations are less as compared to other development factors. Eruption of teeth is one of the changes observed easily among the various dynamic changes that occur from the formation of teeth to the final shedding of teeth. The times of eruption of teeth are fairly constant and this can be made use of in ascertaining the average age of eruption of the tooth. Assessment of age of an individual by examination of teeth is one of the accepted methods of age determination. PMID- 25125912 TI - Pulp tissue in sex determination: A fluorescent microscopic study. AB - AIMS: To determine and compare the reliability of pulp tissue in determination of sex and to analyze whether caries have any effect on fluorescent body test. MATERIALS AND METHODS: This study was carried on 50 maxillary and mandibular teeth (25 male teeth and 25 female teeth), which were indicated for extraction. The teeth are categorized into 5 groups, 10 each (5 from males and 5 from females) on the basis of caries progression. The pulp cells are stained with quinacrine hydrochloride and observed with fluorescent microscope for fluorescent body. Gender is determined by identification of Y chromosome fluorescence in dental pulp. RESULTS: Fluorescent bodies were found to be more in sound teeth in males as the caries increase the mean percentage of fluorescent bodies observed decreases in males. We also observed the fluorescent spots in females, and the value of the spot increases in female as the caries progresses, thereby giving false positive results in females. CONCLUSION: Sex determination by fluorescent staining of the Y chromosome is a reliable technique in teeth with healthy pulps or caries with enamel or up to half way of dentin. Teeth with caries involving pulp cannot be used for sex determination. PMID- 25125913 TI - Quantitative and qualitative assessment of DNA extracted from saliva for its use in forensic identification. AB - Saliva has long been known for its diagnostic value in several diseases. It also has a potential to be used in forensic science. OBJECTIVE: The objective of this study is to compare the quantity and quality of DNA samples extracted from saliva with those extracted from blood in order to assess the feasibility of extracting sufficient DNA from saliva for its possible use in forensic identification. MATERIALS AND METHODS: Blood and saliva samples were collected from 20 volunteers and DNA extraction was performed through Phenol Chloroform technique. The quantity and quality of isolated DNA was analyzed by spectrophotometery and the samples were then used to amplify short tandem repeat (STR) F13 using the polymerase chain reaction. RESULTS: Mean quantity of DNA obtained in saliva was 48.4 +/- 8.2 MUg/ml and in blood was 142.5 +/- 45.9 MUg/ml. Purity of DNA obtained as assessed by the ratio of optical density 260/280, was found to be optimal in 45% salivary samples while remaining showed minor contamination. Despite this positive F13 STR amplification was achieved in 75% of salivary DNA samples. CONCLUSION: Results of this study showed that saliva may prove to be a useful source of DNA for forensic purpose. PMID- 25125914 TI - Comparison of hard tissue interrelationships at the cervical region of teeth based on tooth type and gender difference. AB - CONTEXT: Cementoenamel junction (CEJ) represents the anatomic limit between the crown and root surface. With advancing age and continuous eruption, this area becomes exposed in the oral media. Consequently, CEJ will be subjected to the action of various physical and chemical factors that might alter its morphology, with the cementum being affected in most cases. AIM: To identify the frequency of hard tissue interrelationships present at the CEJ in relation to different genders, positions and aspects of tooth using a light microscope. MATERIALS AND METHODS: The cervical regions of 80 permanent teeth (40 male and 40 female), extracted for orthodontic or periodontal reasons, were analyzed after longitudinal ground sections were made in the mesio-distal plane. The CEJ of the prepared sections was then studied and their frequencies were categorized as: cementum overlapping enamel, enamel overlapping cementum, edge-to-edge relationship and the presence of gap junctions. STATISTICAL ANALYSIS: Chi-square test performed using SPSS 15 software. RESULTS: Edge-to-edge contact of the cementum and enamel was most frequent, followed by gap junction and cementum overlapping the enamel, respectively. Chi-square test revealed no statistically significant differences with respect to the gender and tooth aspect, whereas the result was significant when the position of the tooth was studied. CONCLUSION: The observations of the study indicate a considerable morphological diversity in the anatomical pattern of CEJ. It can be concluded that the region should be protected against dentinal sensitivity, erosion, abrasion, abfraction and resorption, as it is more prone to cervical pathologies. PMID- 25125915 TI - A comparative study to evaluate the vertical position of maxillary central incisor and canine in relation to incisive papilla line. AB - OBJECTIVES: The aim of the study was to determine the vertical distance of maxillary central incisor (CI) and maxillary canine (CA) from the incisive papilla (IP) line and their variation with age and sex. MATERIALS AND METHODS: A total of 120 dentulous subjects following the inclusion and exclusion criteria were randomly selected from the local population. On the basis of gender and age, subjects were divided into four groups: Ma, Mb, Fa and Fb . Maxillary impressions of selected subjects were made and corresponding casts were retrieved. The cast was positioned on the surveyor and the center of IP was transferred to the labial side of maxillary right CI and CA regions with the help of analyzing rod of the surveyor and a line was drawn in this region which was referred to as "IP line". The measurements were made from the IP line to the mesio-incisal line angle of right maxillary CI-IP and cusp tip of right maxillary CA with the help of digital vernier caliper (CA to IP). RESULT: The mean vertical distance of maxillary CI-IP ranged from 6.31 +/- 0.74 mm to 7.04 +/- 0.87 mm and the mean vertical distance of maxillary CA-IP ranged from 5.83 +/- 0.80 mm to 6.30 +/- 0.82 mm. CONCLUSION: The CA position in relation to the IP line is more stable to its position than the CI position irrespective of age and sex. PMID- 25125916 TI - A call for a new speciality: Forensic odontology as a subject. AB - BACKGROUND: Forensic science is defined as a discipline concerned with the application of science and technology to the detection and investigation of crime and administration of justice, requiring the coordinated efforts of a multidisciplinary team. Dental identification remains one of the most reliable and frequently applied methods of identification. Hence, it can be defined as the science that deals with evidence from the dental and oral structures and is a specialty in itself. OBJECTIVES: To analyze the level of awareness of Forensic Odontology amongst the individuals from the field of dentistry with the help of a survey. MATERIALS AND METHODS: A questionnaire was prepared and a survey was conducted with a sample size of 200 divided in four groups. RESULTS: Revealed inadequate knowledge, poor attitude, and lack of practice of forensic odontology prevailing among the dentists. CONCLUSION: Our study reflects the current situation of our country in the field of forensic odontology, which could be improved by introducing forensic odontology as a subject in the dental curriculum at both the undergraduate and the post-graduate levels. PMID- 25125917 TI - Stature and gender determination and their correlation using odontometry and skull anthropometry. AB - BACKGROUND: When the body has been mutilated, it is common to have the extremities or head amputated from the trunk. In concern with forensic odontology, an estimate must have been made based on the correlation of osteometry along with odontometry in determining sex, race and stature. OBJECTIVE: The objective of this study is to investigate and correlate height and gender from odontometry and anthropometric data of the skull. MATERIALS AND METHODS: The study was conducted in the Department of Oral and Maxillofacial Pathology and Microbiology, I.T.S Center for Dental studies and Research, Muradnagar, Ghaziabad (UP) with the representative study subjects of 60 patients as 30 males and 30 females in the age group of 15-25 years. The selected parameters were measured and then correlated to investigate stature and gender from odontometry and anthropometric data of the skull. RESULTS: On linear regression analysis, the selected parameters were found to be statistically significant predictor of height. It was also established by Karl Pearson's coefficient correlation that the left mandibular canine index for female was statistically significant to show sexual dimorphism. CONCLUSION: In the emerging field of forensic odontology, skull anthropometry, odontometry exhibits stature determination and strong sexual dimorphism. PMID- 25125918 TI - Gender determination from pulpal tissue. AB - OBJECTIVE: To evaluate the diagnostic performance of X (Barr body [BB]) and Y (F body [FB]) chromosomes observed in dental pulp tissue for gender determination of an individual. MATERIALS AND METHODS: The study was carried out on 100 teeth (50 male and 50 female), which were indicated for extraction. The teeth were sectioned at various intervals (within 12 h to 49 days post-extraction), and the pulpal tissue was obtained. Two slides for each pulp tissue were prepared, one for 5% Quinacrine dihydrochloride stain (FB) and the other for Hemotoxylin and Eosin stain (BB). The slides were then observed under the fluorescent microscope for FB and under the light microscope for the BB respectively. RESULTS: Gender determination from human pulp is possible up to 7 weeks. The percentage of FB and BB decrease gradually as the time interval increases. Further, an equation was derived from the data based on the canonical discriminant function coefficients. CONCLUSION: The determination of gender based on a joint search for the presence or absence of X (BB) and Y (FB) Chromosome is a reliable and cost-effective technique. PMID- 25125919 TI - Age estimation from physiological changes of teeth: A reliable age marker? AB - BACKGROUND: Age is an essential factor in establishing the identity of a person. Teeth are one of the most durable and resilient part of skeleton. Gustafson (1950) suggested the use of six retrogressive dental changes that are seen with increasing age. AIM: The aim of the study was to evaluate the results and to check the reliability of modified Gustafson's method for determining the age of an individual. MATERIALS AND METHODS: Total 70 patients in the age group of 20-65 years, undergoing extraction were included in this present work. The ground sections of extracted teeth were prepared and examined under the microscope. Modified Gustafson's criteria were used for the estimation of age. Degree of attrition, root translucency, secondary dentin deposition, cementum apposition, and root resorption were measured. A linear regression formula was obtained using different statistical equations in a sample of 70 patients. RESULTS: The mean age difference of total 70 cases studied was +/-2.64 years. Difference of actual and calculated age was significant and was observed at 5% level of significance, that is, t-cal > t-tab (t-cal = 7.72). P < 0.05, indicates that the results were statistically significant. CONCLUSION: The present study concludes that Gustafson's method is a reliable method for age estimation with some proposed modifications. PMID- 25125920 TI - Rugae pattern in a sample of population of Meerut - An institutional study. AB - CONTEXT: Many studies on rugae pattern have been done on various samples of population, but no study has so far been done to assess the rugae pattern of population of western Uttar radesh, especially Meerut. AIMS: This study was aimed to assess the rugae pattern in males and females of a sample of population of Meerut, which may be an additional method of determining gender when dealing with any crime or with mutilated bodies that have undergone damage beyond recognition. SETTINGS AND DESIGN: A total of 100 Class I dentulous subjects, 50 male and 50 female patients reporting to the outpatient department of Kalka Dental College, Meerut, Uttar Pradesh were randomly selected with an age range between 20-30 years. Exclusion criteria were subjects >14 years of age, congenital malformations, previous orthognathic surgery, allergy to impression material, bony and soft tissue protuberances, active lesions, deformity or scars and trauma of the palate. Prior approval from the Institutional Ethical Committee was taken. SUBJECTS AND METHODS: Alginate impressions of palate of selected patients were poured in dental stone and rugae pattern was identified and analyzed by a single rater employing Thomas and Kotze's (1983) method. STATISTICAL ANALYSIS USED: Two sample t-test and Chi-Square tests were used for comparison of means and relationship between the attributes. A significance level of 5% was considered as critical value. RESULTS: No significant difference was noted in total number or length of rugae between the genders. However, statistically significant difference in the circular type in males and converge type in females was observed. CONCLUSION: Rugae pattern can be used as a method of differentiation between males and females to corroborate the findings of other methods such as anthropometric evaluation of the cranium and dental characteristics. PMID- 25125921 TI - Experimental model of developing and analysis of lip prints in atypical surface: A metallic straw (bombilla). AB - BACKGROUND: The interaction between the offender and the victim produces visible or latent prints on objects and utensils. The study of lip prints has reportedly stayed away from the basic cinematic concept of the lip-to-surface relationship. MATERIALS AND METHODS: Three regular powders were used to reveal the latent lip prints on a typical metallic straw called bombilla, and the revealed prints were photographed, preserved, and analyzed. RESULTS: Better definition was observed in the lower lip print, and nine anatomical patterns were identified, but a higher definition of wrinkles was observed with indestructible white powder. CONCLUSION: Knowledge of labial dynamics, the real value of the processed surfaces, and the need for testing in field conditions are discussed. PMID- 25125922 TI - Molecular sex identification of dry human teeth specimens from Sokoto, Northwestern Nigeria. AB - BACKGROUND: The advent of molecular techniques has revolutionized the ability of scientists to estimate the sex of individuals. Forensic odontology plays an important role in establishing the sex of victims with bodies mutilated beyond recognition due to major disaster. The genetic difference between males and females is defined by the presence or absence of the Y-chromosome. The use of alphoid-repeat primers in sex estimation was first applied on dried blood. Generally, the X, Y alphoid repeats blind test attest to the accuracy of genetic testing, and also point the potential for occasional error in morphometric sexing. AIM: To estimate genetic sex of dry human teeth specimens from Sokoto, Northwestern Nigeria, using polymerase chain reaction (PCR). MATERIALS AND METHODS: A single-blind study of DNA analysis for sex estimation of nine dry human teeth specimens from Sokoto, Northwestern Nigeria, through PCR, using alphoid repeats primers, was undertaken. RESULTS: The genetic sex of each group of the teeth samples were accurately (100%) identified. For each group of teeth, PCR Sensitivity = 100%, Specificity = 0%, Predictive value of positive test = 100%, Predictive value of negative test = 0%, False positive rate = 0%, False negative rate = 0%, Efficiency of test = 100%. Fisher's exact probability test P = 1. Z-test: z- and P values were invalid. CONCLUSION: This study has demonstrated the successful use of alphoid-repeat primers in genetic sex identification of human dry teeth samples from Sokoto, Northwestern Nigeria. This is the first known study estimating the sex of human dry teeth specimens by means of PCR in Nigeria. There is need for further studies in Nigeria to complement the findings of this study. PMID- 25125924 TI - Role of dental implants in forensic identification. PMID- 25125923 TI - Volume analysis of heat-induced cracks in human molars: A preliminary study. AB - CONTEXT: Only a few methods have been published dealing with the visualization of heat-induced cracks inside bones and teeth. AIMS: As a novel approach this study used nondestructive X-ray microtomography (micro-CT) for volume analysis of heat induced cracks to observe the reaction of human molars to various levels of thermal stress. MATERIALS AND METHODS: Eighteen clinically extracted third molars were rehydrated and burned under controlled temperatures (400, 650, and 800 degrees C) using an electric furnace adjusted with a 25 degrees C increase/min. The subsequent high-resolution scans (voxel-size 17.7 MUm) were made with a compact micro-CT scanner (SkyScan 1174). In total, 14 scans were automatically segmented with Definiens XD Developer 1.2 and three-dimensional (3D) models were computed with Visage Imaging Amira 5.2.2. The results of the automated segmentation were analyzed with an analysis of variance (ANOVA) and uncorrected post hoc least significant difference (LSD) tests using Statistical Package for Social Sciences (SPSS) 17. A probability level of P < 0.05 was used as an index of statistical significance. RESULTS: A temperature-dependent increase of heat induced cracks was observed between the three temperature groups (P < 0.05, ANOVA post hoc LSD). In addition, the distributions and shape of the heat-induced changes could be classified using the computed 3D models. CONCLUSION: The macroscopic heat-induced changes observed in this preliminary study correspond with previous observations of unrestored human teeth, yet the current observations also take into account the entire microscopic 3D expansions of heat induced cracks within the dental hard tissues. Using the same experimental conditions proposed in the literature, this study confirms previous results, adds new observations, and offers new perspectives in the investigation of forensic evidence. PMID- 25125928 TI - Effect of Silver Coating on Barium Titanium Oxide Nanoparticle Toxicity. AB - Nanoparticles are presently being studied for optical and biomedical applications such as medical imaging and drug delivery. Nanoparticles impact the cellular environment due to many variables such as size, shape, and composition. How these factors affect cell viability is not fully understood. The purpose of this study is to test the toxicity effects of silver coating (Ag@) Barium Titanium Oxide (BaTiO3) nanoparticles on Rhesus Monkey Retinal Endothelial cells (RhREC's) in culture. The addition of silver to the nanoparticles increases their nonlinear optical properties significantly, making the Ag@BaTiO3 nanoparticles good candidates for nonlinear microscopy contrast agents. We hypothesize that by silver coating nanoparticles, there will be an increase in cell viability at higher concentrations when compared to non-silver coated nanoparticles. RhREC's were treated with BaTiO3 and Ag@BaTiO3 at concentrations of 0, 1.0, 10.0, and 100ug/ml for 24 hours at 37 degrees C + 5%CO2. After 24 hour incubation with respective nanoparticles, cell viability was determined using the trypan blue dye exclusion method. Treatment with 0, 1.0 and 10.0ug/ml of Ag@BaTiO3 had minimal effect on cell viability, with 90% viable cells remaining at the end of the 24 hours treatment period. However, cells treated with 100ug/ml of Ag@BaTiO3 resulted in a decrease to 51% viable cells. Comparatively, cells treated with 0, 1.0 and 10ug/ml of BaTiO3 had no significant effect on cell viability (90% viable cells after treatment) while the 100ug/ml treatment resulted in a decrease to 29% viable cells. These results show that silver coating of BaTiO3 nanoparticles has a protective effect on cellular toxicity at high concentrations. PMID- 25125929 TI - SUPPORT FOR THE CONTINUATION OF FEMALE GENITAL MUTILATION AMONG ADOLESCENTS IN JIMMA ZONE, SOUTHWEST ETHIOPIA. AB - BACKGROUND: Female genital mutilation/cutting is a harmful practice which has effect on female's wellbeing. However, the practice has continued to prevail in many cultures. Research on the social determinants of the practice and its continuation are scarce. The objective of this study was to assess whether attitude towards the continuation of female genital mutilation is predicted by gender role perception among adolescents in Jimma zone. METHODS: This study used data collected in the first round of Jimma Longitudinal Family Survey of Youth. A total of 2084 adolescents were identified from 3700 households and one adolescent were interviewed from each household using structured questionnaire. Data on the socio-demographic characteristics, religiosity, access to electronic media, perception of gender role, attitude towards continuation of Female circumcision was collected. Descriptive and multivariate statistical techniques were used to analyze the data using SPSS for windows version 16.0. Statically tests were performed at the level of significance of 5%. RESULTS: Of the 2084 adolescents, 1146 (55.0%) were aged 12-14 years, 1025 (49.2%) females and 749 (35.9%) from rural areas. The majority, 1289 (61.9%) were Muslims and 1351 (64.8%) Oromo. Five hundred seventy three (28.1%) of the male youth did not agree to the importance of marrying a circumcised girl. However, 149 (13.8%) and 258 (12.7%) agreed that it is very important and important, to marry a circumcised girl, respectively. On multivariate logistic regression analysis, perception of gender role, sex, place of residence, highest education in the household and religion remained to be important predictors of attitude towards the continuation of female genital mutilation after adjustment for age and ethnicity. Adolescents who had low gender role perception were 1.4 times more likely to have a positive attitude towards the continuation of the female genital mutilation (OR: 95%CI, 1.41: 1.02-1.94). Female adolescents were 36% less likely to support (P<0.01) the continuation of FGM compared to their male counter parts (OR: 0.64; 95%CI: 0.49, 0.83). Compared to urban youth, those who live in semi urban and rural areas were 1.46 and 1.52 times more likely to have a positive attitude towards the continuation of the FGM practice, respectively (P<0.05). Similarly the Probability of having positive attitude towards the continuation of the FGM practice decreased steadily as the highest educational level in the household increased. CONCLUSION: One-fifth of the youth support the continuation of the practice. Low gender roles perception, being from the rural areas, household's lower level of education and being Muslim were strong predictors of the attitude towards the continuation of female genital mutilation. Improving perception of adolescents towards gender roles through effective behavior change communication, and involving religious leaders in the campaign against the practice of female genital mutilation is recommended as a useful strategy to ban the practice. PMID- 25125930 TI - Substance Use as a Risk Factor for Intimate Partner Violence Overlap: Generational Differences Among Hispanic Young Adults. AB - Intimate partner violence (IPV) research often focuses on either the victims of IPV or the perpetrators of IPV. Recent studies have documented the existence of a group of victim-perpetrators, for example, they perpetrate IPV and are also the victims of IPV. The current study examines this overlap in IPV perpetration and victimization among a nationally representative, longitudinal sample of 1,488 Hispanics with a focus on generational status. Results from group-based trajectory models and survey multinomial regression techniques suggest that alcohol and marijuana use over time are salient risk factors for IPV perpetration, IPV victimization, and IPV overlap. Study limitations and implications are discussed. PMID- 25125931 TI - Moral Violations Reduce Oral Consumption. AB - Consumers frequently encounter moral violations in everyday life. They watch movies and television shows about crime and deception, hear news reports of corporate fraud and tax evasion, and hear gossip about cheaters and thieves. How does exposure to moral violations influence consumption? Because moral violations arouse disgust and because disgust is an evolutionarily important signal of contamination that should provoke a multi-modal response, we hypothesize that moral violations affect a key behavioral response to disgust: reduced oral consumption. In three experiments, compared with those in control conditions, people drank less water and chocolate milk while (a) watching a film portraying the moral violations of incest, (b) writing about moral violations of cheating or theft, and (c) listening to a report about fraud and manipulation. These findings imply that "moral disgust" influences consumption in ways similar to core disgust, and thus provide evidence for the associations between moral violations, emotions, and consumer behavior. PMID- 25125932 TI - The influence of spinal manipulation on the practitioner-something to consider in our instruction of manual therapy? PMID- 25125934 TI - The relationship between various anatomical landmarks used for localizing the first rib during surface palpation. AB - OBJECTIVES: To assess the relationship between anatomical landmarks used to locate the first rib during surface palpation. One currently cited technique suggests locating the width of the transverse processes (TPs) of the first cervical vertebrae (C1) to determine the estimated width of the first thoracic vertebrae (T1) TP, allowing for subsequent palpation of the first rib laterally to the transverse process of T1. Based on anatomical structural relationships, the authors propose an additional method of locating the first rib, lateral to T1 TP, by palpating through the trapezius muscle at the width of the mastoid process (MP). METHODS: Overlying tissue of the bilateral MP, C1 TPs, and T1 TPs of 28 cadavers were removed. Measurements of the left to right spans at the following structures were collected using a digital caliper: mastoid process, C1 TP, and T1 TP. Measurements were used to determine the agreement between each anatomical structural span. RESULTS: The mean absolute difference (standard deviation, SD) between C1 TP span versus T1 TP span was 3.9 (+/-2.58) mm with an intraclass correlation coefficient (ICC) of 0.88 (95% CI = 2.9-4.9). The mean absolute difference between MP span and T1 TP span was 35.4 (+/-6.46) mm with an ICC of 0.71 (95% CI = 33.0-37.8). DISCUSSION: This study confirms the anatomical accuracy and feasibility of using the C1 TP span to determine the general width of the T1 TP span while palpating for the first rib just lateral to the T1 TP. Additionally, this study demonstrates that the more easily palpated mastoid process serves as an effective landmark to identify a width sufficiently lateral to the T1 TP, appropriate for first rib palpation through the trapezius muscle. PMID- 25125933 TI - The effectiveness of strain counterstrain in the treatment of patients with chronic ankle instability: A randomized clinical trial. AB - STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To determine the effect of strain counterstrain (SCS) on dynamic balance and subjective sense of instability in individuals with chronic ankle instability (CAI). Although many studies have been published on CAI, the cause for this common clinical dysfunction remains inconclusive. No studies have assessed the effectiveness of SCS on CAI. METHODS: At baseline all participants completed a demographic questionnaire, the star excursion balance test (SEBT), and the foot and ankle ability measure (FAAM). Following the baseline evaluation, participants were randomized into the SCS experimental group (EG) (n = 13) or the sham SCS group (SG) (n = 14). All participants received the assigned treatment once a week for 4 weeks and participated in a prescribed exercise program. At week 4, all participants repeated the outcome measures and completed a global rating of change (GROC) form. The primary aim was examined with a two-way analysis of variance (ANOVA). RESULTS: A significant group-by-time interaction was found for seven directions in the SEBT (P<0.031). For subjective measures, no significant group-by-time interaction was found for the FAAM (P>0.548), but the GROC revealed a significant difference (P = 0.014) in the mean score for the EG (3.92+/-1.66) when compared to the SG (2.43+/-1.66). DISCUSSION: Although SCS may not have an effect on subjective ankle function in individuals with CAI, preliminary evidence suggests that SCS may lead to an improvement in dynamic ankle stability and the subjective sense of ankle instability. LEVEL OF EVIDENCE: Therapy, Level 1b. PMID- 25125935 TI - Adverse events following trigger point dry needling: a prospective survey of chartered physiotherapists. AB - OBJECTIVES: Trigger point dry needling (TrP-DN) is commonly used to treat persons with myofascial pain, but no studies currently exist investigating its safety. The aim of this study was to determine the incidence of Adverse Events (AEs) associated with the use of TrP-DN by a sample of physiotherapists in Ireland. METHODS: A prospective survey was undertaken consisting of two forms recording mild and significant AEs. Physiotherapists who had completed TrP-DN training with the David G Simons Academy (DGSA) were eligible to take part in the study. Data were collected over a ten-month period. RESULTS: In the study, 39 physiotherapists participated and 1463 (19.18%) mild AEs were reported in 7629 treatments with TrP-DN. No significant AEs were reported giving an estimated upper risk rate for significant AEs of less than or equal to (<=) 0.04%. Common AEs included bruising (7.55%), bleeding (4.65%), pain during treatment (3.01%), and pain after treatment (2.19%). Uncommon AEs were aggravation of symptoms (0.88%), drowsiness (0.26%), headache (0.14%), and nausea (0.13%). Rare AEs were fatigue (0.04%), altered emotions (0.04%), shaking, itching, claustrophobia, and numbness, all 0.01%. DISCUSSION: While mild AEs were very commonly reported in this study of TrP-DN, no significant AEs occurred. For the physiotherapists surveyed, TrP-DN appeared to be a safe treatment. PMID- 25125936 TI - Thoracic manipulation versus mobilization in patients with mechanical neck pain: a systematic review. AB - OBJECTIVES: Thoracic manipulation is widely used in physical therapy and has been shown to be effective at addressing mechanical neck pain. However, thoracic mobilization may produce similar effects. The purpose of this systematic review was to evaluate the current literature regarding the effectiveness of thoracic manipulation versus mobilization in patients with mechanical neck pain. METHODS: ProQuest, NCBI-PubMed, APTA's Hooked on Evidence, Cochrane Library, CINAHL and SPORTDiscus were searched to identify relevant studies. Fourteen studies meeting the inclusion criteria were analyzed using the Physiotherapy Evidence Database (PEDro) scale and the GRADE approach. RESULTS: The literature as assessed by the PEDro scale was fair and the GRADE method showed overall quality ranging from very low to moderate quality. The 14 included studies showed positive outcomes on cervical pain levels, range of motion, and/or disability with the use of thoracic manipulation or mobilization. There was a paucity of literature directly comparing thoracic manipulation and mobilization. DISCUSSION: Current limitations in the body of research, specifically regarding the use of thoracic mobilization, limit the recommendation of its use compared to thoracic manipulation for patients with mechanical neck pain. There is, however, a significant amount of evidence, although of varied quality, for the short-term benefits of thoracic manipulation in treating patients with this condition. Further high quality research is necessary to determine which technique is more effective in treating patients with mechanical neck pain. PMID- 25125937 TI - Accuracy of physical therapists' prognosis of low back pain from the clinical examination: a prospective cohort study. AB - OBJECTIVES: To investigate, in patients with chronic or recurrent low back pain (LBP), the predictive validity of history items, demographic variables, outcome measure questionnaire scores, clinical examination items, and physical therapists' (PTs') summative estimation of prognosis on a four-point scale. Little is known about the ability of PTs to predict functional outcomes for patients with LBP. METHODS: This was a multi-centre prospective cohort study of 138 patients with LBP. We used backward stepwise linear regression modelling to estimate the predictive validity of the baseline variables. The endpoint outcome measure was the 18-item Roland-Morris Disability Questionnaire (RM18) at 1 year. RESULTS: Of 138 patients with LBP recruited, 89 (64%) completed follow-up at one year. Univariate analysis indicated that PTs' opinion of prognosis (P = 0.01) and eleven other baseline variables were significantly associated with RM18 at 12 months. In the final multivariate model PTs' opinion of prognosis (P = 0.022; beta = 0.73, CI 0.55, 0.95), an abnormality detected by passive physiological flexion testing (P = 0.043, beta = 1.61, CI 1.02, 2.57), heavy work (P = 0.069, beta = 0.80, CI 0.62, 1.01), and age (P = 0.079, beta = 1.01 CI 0.99, 1.04) were independent prognostic factors for RM18 outcome, explaining 24% of the variance in the model. CONCLUSIONS: Musculoskeletal PTs' summative clinical impression regarding prognosis, following a clinical examination, provides a valid predictive estimation of functional outcome at 1 year in patients with chronic or recurrent LBP. PMID- 25125938 TI - Metastatic cancer mimicking mechanical low back pain: a case report. AB - OBJECTIVE AND IMPORTANCE: The purpose of this report is to describe the clinical course of a patient referred to physiotherapy (PT) for the treatment of low back pain who was subsequently diagnosed with metastatic non-small cell carcinoma of the lung. CLINICAL PRESENTATION: A 48-year old woman was referred to PT for the evaluation and treatment of an insidious onset of low back pain of 2 month duration. The patient did not have a history of cancer, recent weight changes, or general health concerns. The patient's history and physical examination were consistent with a mechanical neuromusculoskeletal dysfunction and no red flag findings were present that warranted immediate medical referral. INTERVENTION: Short-term symptomatic improvements were achieved using the treatment-based classification approach. However, despite five PT sessions over the course of 5 weeks, the patient did not experience long-term symptomatic improvement. On the sixth session, the patient reported a 2-day history of left hand weakness and headaches. This prompted the physiotherapist to refer the patient to the emergency department where she was diagnosed with lung cancer. CONCLUSION: Differential diagnosis is a key component of PT practice. The ability to reproduce symptoms or achieve short-term symptomatic gains is not sufficient to rule out sinister pathology. This case demonstrates how extra caution should be taken in patients who are smokers with thoracolumbar region pain of unknown origin. The need for caution is magnified when one can achieve no more than short term improvements in the patient's symptoms. PMID- 25125939 TI - Clinical Correlates of Autosomal Chromosomal Abnormalities in an Electronic Medical Record-Linked Genome-Wide Association Study: A Case Series. AB - Although mosaic autosomal chromosomal abnormalities are being increasingly detected as part of high-density genotyping studies, the clinical correlates are unclear. From an electronic medical record (EMR)-based genome-wide association study (GWAS) of peripheral arterial disease, log-R-ratio and B-allele-frequency data were used to identify mosaic autosomal chromosomal abnormalities including copy number variation and loss of heterozygosity. The EMRs of patients with chromosomal abnormalities and those without chromosomal abnormalities were reviewed to compare clinical characteristics. Among 3336 study participants, 0.75% (n = 25, mean age = 74.8 +/- 10.7 years, 64% men) had abnormal intensity plots indicative of autosomal chromosomal abnormalities. A hematologic malignancy was present in 8 patients (32%), of whom 4 also had a solid organ malignancy while 2 patients had a solid organ malignancy only. In 50 age- and sex-matched participants without chromosomal abnormalities, there was a lower rate of hematologic malignancies (2% vs 32%, P < .001) but not solid organ malignancies (20% vs 24%, P = .69). We also report the clinical characteristics of each patient with the observed chromosomal abnormalities. Interestingly, among 5 patients with 20q deletions, 4 had a myeloproliferative disorder while all 3 men in this group had prostate cancer. In summary, in a GWAS of 3336 adults, 0.75% had autosomal chromosomal abnormalities and nearly a third of them had hematologic malignancies. A potential novel association between 20q deletions, myeloproliferative disorders, and prostate cancer was also noted. PMID- 25125941 TI - Cu(II) Catalytic Reduction of Cr(VI) by Tartaric Acid Under the Irradiation of Simulated Solar Light. AB - Cu(II) catalytic reduction of Cr(VI) by tartaric acid under the irradiation of simulated solar light was investigated through batch experiments at pHs from 3 to 6 and at temperatures from 15 degrees C to 35 degrees C. Results demonstrated that introduction of Cu(II) could markedly improve reduction of Cr(VI) in comparison with tartaric acid alone. Optimal removal of Cr(VI) was achieved at pH 4. Reduction of Cr(VI) increased with increasing temperatures and initial concentrations of Cu(II) and tartaric acid. The catalytic role of Cu(II) in the reduction of Cr(VI) was ascribed to the formation of Cu(II)-tartaric acid complex, which generated active reductive intermediates, including Cu(I) and tartaric acid radicals through a pathway of metal-ligand-electron transfer with light. Cu(II) photocatalytic reduction of Cr(VI) by tartaric acid followed pseudo zero-order kinetics with regard to Cr(VI), and the activation energy was calculated to be 21.48 kJ/mol. To date, such a role of Cu(II) has not been reported. The results from the present study are helpful in fully understanding the photochemical reductive behavior of Cr(VI) in the presence of both tartaric acid and Cu(II) in soil and aquatic environments. PMID- 25125940 TI - Social-Cognitive Moderators of the Relationship between Peer Victimization and Suicidal Ideation among Psychiatrically Hospitalized Adolescents. AB - Peer victimization among children and adolescents is a major public health concern, given its widespread individual and societal ramifications. Victims of peer aggression often face significant levels of psychological distress and social difficulties, such as depression, suicidal ideation, suicide attempts, and social rejection. The purpose of the present study was to examine whether cognitive distortions and perceptions of social support moderate the association between peer victimization and suicidal thoughts among psychiatrically hospitalized adolescents. Participants included 183 psychiatrically hospitalized adolescents (ages 13-18). In multiple regression analyses that controlled for gender, social and cognitive factors served as significant resources factors. Cognitive factors also moderated the relationship between peer victimization and suicidal ideation. PMID- 25125942 TI - A Multistep Chaotic Model for Municipal Solid Waste Generation Prediction. AB - In this study, a univariate local chaotic model is proposed to make one-step and multistep forecasts for daily municipal solid waste (MSW) generation in Seattle, Washington. For MSW generation prediction with long history data, this forecasting model was created based on a nonlinear dynamic method called phase space reconstruction. Compared with other nonlinear predictive models, such as artificial neural network (ANN) and partial least square-support vector machine (PLS-SVM), and a commonly used linear seasonal autoregressive integrated moving average (sARIMA) model, this method has demonstrated better prediction accuracy from 1-step ahead prediction to 14-step ahead prediction assessed by both mean absolute percentage error (MAPE) and root mean square error (RMSE). Max error, MAPE, and RMSE show that chaotic models were more reliable than the other three models. As chaotic models do not involve random walk, their performance does not vary while ANN and PLS-SVM make different forecasts in each trial. Moreover, this chaotic model was less time consuming than ANN and PLS-SVM models. PMID- 25125943 TI - Greek financial crisis: consequences in the healthcare of diabetes and its complications. PMID- 25125944 TI - Functional hyposplenism. AB - Functional hyposplenism is a condition accompanying many diseases such as sickle cell disease, celiac disease, alcoholic liver disease, hepatic cirrhosis, lymphomas and autoimmune disorders. It is characterised mostly by defective immune responses against infectious agents, especially encapsulated organisms, since the spleen is thought to play an important role in the production and maturation of B-memory lymphocytes and other substances like opsonins, both of which are considered crucial elements of the immune system for fighting infections. It is also associated with thrombocytosis, which might lead to thromboembolic events. Functional hyposplenism is diagnosed by the presence of Howell-Jolly bodies and pitted erythrocytes in the peripheral blood smear, and by nuclear imaging modalities such as spleen scintigraphy with the use of Technetium 99m and/or spleen scintigraphy with the use of heat-damaged Technetium-99m labeled erythrocytes. Severe infections accompanying functional hyposplenism can lead to the overwhelming post infection syndrome, which can often be fatal. Identifying patients with functional hyposplenism is important because simple measures such as vaccination against common infective microorganisms (e.g. Streptococcus pneumonia, Neisseria meningitides and Haemophilous influenzae) and antibiotic therapy when needed are considered beneficial in diminishing the frequency and gravity of the infections accompanying the syndrome. PMID- 25125945 TI - Wall shear stress oscillation and its gradient in the normal left coronary artery tree bifurcations. AB - BACKGROUND: It is known that blood flow properties such as low/ oscillatory wall shear stress (WSS), high blood viscosity, low blood velocity and high concentration of low density lipoprotein (LDL) macromolecules, are some of the main flow parameters causing atherosclerosis. Limited research has been undertaken on the pulsatile WSS and WSS gradient (WSSG) analysis focusing in the differentiation between the bifurcation itself and the lateral to it walls in a normal left coronary artery (LCA). The results obtained show the flow characteristics and qualify the spatial and temporal distribution of WSS ant its gradient in regions close to the LCA tree flow dividers and in opposite to them areas. METHODS: A 3D computer generated model of the LCA tree based on averaged human data extracted from angiographies was developed for computational fluid dynamics analysis. Physiological phasic flow velocity is incorporated as entrance boundary condition. RESULTS: The instantaneous min wall shear stress oscillates from 0.45 to 2.84 N/m(2) at the flow divider and from 0.25 to 1.28 N/m(2) at the lateral walls of the main bifurcation. However, for the D1-S1 bifurcation (first diagonal-first septal), the instantaneous min wall shear stress oscillates from 0.6 to 3.85 N/m(2) at the flow divider and from 0.6 to 2.65 N/m(2) at the lateral walls. Mean wall shear stress, from max systole to max diastole, experiences a 129.0 % increase at the main bifurcation flow divider. The difference between max and min wall shear stress for the flow divider of the main bifurcation, as it is compared with the max wall shear stress over the entire cardiac pulse, attains a maximum value of 81.1 % for the lateral walls and 60.0 % at the peak of diastole. At the D1-S1 bifurcation, the corresponding difference values are 69.0% and 57.0 % for the lateral walls and flow divider, respectively. The mean wall shear stress gradient experiences a 123.0 % increase from max systole to max diastole at the main bifurcation flow divider and 153.0 % at main bifurcation lateral walls. CONCLUSIONS: Proximal LCA bifurcation exhibit lower spatial wall shear stress and lower wall shear stress gradient values compared to distal bifurcations. The lateral walls compared to the bifurcation itself are exposed to low WSS and WSSG. With regards to the temporal variation, wall shear stress and its gradient exhibited lower values throughout systole as compared to diastole, suggesting a possible atherogenic effect of both the systolic phase by itself as well as the phasic oscillation of wall shear stress and its gradient from systole to diastole. PMID- 25125946 TI - N-acetylcycsteine attenuates the deleterious effects of radiation therapy on inci sional wound healing in rats. AB - BACKGROUND: During preoperative radiotherapy, effective doses of ionizing radiation occasionally cause wound complications after subsequent surgery. This study was designed to determine the effects of intraperitoneally or orally administered N-acetylcysteine (NAC) on anastomotic healing of irradiated rats. MATERIAL & METHODS: Forty Wistar albino rats were randomized into four groups containing 10 rats each. A 3 cm long surgical full-thickness midline laparotomy was performed to all groups (Groups 1-4). Group 1 was designed as a control group without radiation therapy and NAC treatment. Groups 2, 3 and 4 received a single abdominal dose of 10 Gy irradiation before laparotomy and groups 3 and 4 received oral and intraperitoneal NAC, respectively. RESULTS: Group comparisons demonstrated that breaking strength was significantly higher in NAC treated rats. A statistically significant difference was determined in terms of superoxide dismutase (SOD), malondealdehyde (MDA) and glutation (GSH) values between groups (p<0.001). Nevertheless, advanced oxidation protein products (AOPP) levels were found to be similar between groups (p=0.163). Serum GSH and SOD levels were significantly higher in groups 3 and 4 when compared to group 2 (p < 0.05). Similarly, there was a significant increase in serum MDA concentration, predicting lipid peroxidation, in group 2 when compared to groups 1, 3 and 4 (p < 0.05). There was not a significant difference between Groups 3 and 4 regarding GSH, MDA, SOD, and AOPP levels. Histopathological analysis revealed that NAC administration, either orally or intraperitoneally, leads to a better incisional healing in terms of inflammation, granulation, collagen deposition, reepithelization and neovascularization. CONCLUSION: The present study supports the hypothesis that NAC administration alleviates the negative effects of radiotherapy on incisional wound healing by means of reducing oxidative stress markers and improving histologic parameters independent of the route of administration. PMID- 25125947 TI - Prevalence and molecular epidemiology of methicillin-resistant Staphylococcus aureus in a tertiary Greek hospital. AB - BACKGROUND/AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of health- and community-associated infections; its prevalence in Greece is among the highest in Europe. We investigated the prevalence and molecular epidemiology of MRSA in a tertiary Greek hospital. MATERIAL AND METHODS: Spa typing and random polymorphic DNA analysis were used to investigate the molecular epidemiology of 28 MRSA isolates during May 2010 to May 2011 in a tertiary hospital in Northern Greece. RESULTS: Nine spa types were detected; t003 was the predominant (32.1%) one, detected in various wards and throughout the study period, while t037 was recovered only from intensive care unit patients, and only in April 2011, suggestive of an epidemic. Additional rare types were detected for the first time in Greece. CONCLUSIONS: Spa typing and random polymorphic DNA analysis gave an insight into the epidemiology of MRSA in a Northern Greece hospital. Concerning the distribution in the hospital, the predominant spa type t003 was present in various wards, and was constantly detected throughout the study period, very suggestive of an epidemic, while other types were detected only in specific wards. Our data underline the need for surveillance, typing and constant reassessment of existing strategies to control MRSA. PMID- 25125948 TI - Comparison of analgesic efficiency between wound site infiltration and ultra sound-guided transversus abdominis plane block after cesarean delivery under spinal anaesthesia. AB - BACKGROUND: [corrected] Local anesthetic infiltration applied on the wound site or abdominal wall may be used for relieving postoperative pain after delivery by caesarean section. The aim of this study was to compare the analgesic efficiency of ultrasound (USG)-guided transversus abdominis plane (TAP) block with local anesthetic infiltration on a wound site. METHODS: This study was designed as a prospective randomized trial, and consisted of 70 pregnant women of American Society of Anesthesiologists (ASA) class I-II. Patients were randomized into Group I (wound site infiltration, n=35) and Group T (TAP block, n=35). Spinal anaesthesia was administered to all patients. In Group I, wound site infiltration was applied by the surgical team. In Group T, a USG-guided bilateral TAP block was applied. Patients' numeric pain scale (NPS) levels at 2, 6, 12 and 24(th) hours, after the operation (NPS0) and during mobilization were assessed. Postoperative complications, time to first analgesic request and patient satisfaction were recorded. RESULTS: The NPS0 values of Group T were found to higher and time to first analgesic request longer than those of Group I. The NPS values of Group I at 2, 6, 12, and 24(th) hours were found to be statistically significantly higher than those of Group T. CONCLUSIONS: According to our results, USG-guided TAP block might be superior to infiltration anaesthesia for postoperative pain management of patients who have had caesarean section and it provided longer-lasting and more efficient analgesia. PMID- 25125949 TI - Ultrastructural aspects of the effects of L-carnitine administration on epithelial cells in the aging rat tongue. AB - BACKGROUND: The investigators hypothesized that degenerative changes accumulate in epithelial cells in the aging rat tongue and that carnitine administration is effective at reversing these alterations. MATERIAL AND METHODS: To gain insights into the effects of carnitine on epithelial cells of the tongue, the investigators used 15 Wistar rats [3 experimental groups: 5- (A), 12- (B) and 18- (C) month old rats] with 4 rats per group and 1 control group with 1 rat per age group). L-carnitine was administered intraperitoneally to animals of the experimental group for 35 days. Samples of the tongue were processed for electron microscopy. RESULTS: Degeneration of epithelial cells of the rat tongue was shown to begin early in life (5 months) and alterations were shown to accumulate while aging. L-carnitine administration eliminated degenerative changes when administered in the first age group A, while in the older rats the regeneration was only partial for the epithelium (groups B and C). CONCLUSIONS: The results of this study suggest that profound ultrastructural alterations commence in the degenerating rat tongue and that L-carnitine administration results into partial regeneration of epithelial cells. PMID- 25125950 TI - Effect of exhaust emissions on carbon monoxide levels in employees working at indoor car wash facilities. AB - BACKGROUND: Exhaust emissions from motor vehicles threaten the environment and human health. Carbon monoxide (CO) poisoning, especially the use of exhaust gas CO in suicidal attempts is well known in the literature. Recently, indoor car wash facilities established in large shopping malls with closed parking, lots is a new risk area that exposes car wash employees to prolonged periods of high level CO emissions from cars. The aim of this study was to investigate how carboxyhemoglobin (COHb) blood levels of employees get affected in confined areas with relatively poor air circulation. METHODS: Twenty male volunteers working in indoor parking car wash facilities were included in the study. Participants were informed about the aim of this study and their consent was obtained. Their pulse COHb levels were measured twice, at the beginning and at the end of the working day using Rad-57 pulse CO-oximeter device, allowing non-invasive measurement of COHb blood levels to compare the changes in their COHb levels before and after work. RESULTS: The mean age of the male volunteers was 29.8 +/- 11.9 (range 18 55). While the mean COHb levels measured at the start of the working day was 2.1 +/- 2.0 (range 0-9), it was increased to 5.2 +/- 3.3 (range 1-15) at the end of work shift (Wilcoxon test, p <0.001). There was a statistically significant difference in COHb levels between the beginning and the end of the work shift in smoker subjects, while the difference was not significant in the non-smoking group (Wilcoxon test, p=0.001, p=0.102, respectively). CONCLUSION: The COHb blood levels of indoor car wash facility employees is directly impacted and gets elevated by motor vechile exhaust emissions. For the health of the employees at indoor parking car wash facilities, stricter precautions are needed and the government should not give permit to such operations. PMID- 25125951 TI - Complications of automated spring fired biopsy gun technique. A retrospective analysis of 230 cases. AB - BACKGROUND: Renal biopsy (RB) is a procedure which allows obtaining kidney tissue for a morphological diagnosis. As an invasive procedure, RB could lead to some complications. The aim of the study was to assess the incidence and the severity of various complications of renal biopsy(RB) performed by automated spring fired biopsy gun with needles 16 and 18G. MATERIAL AND METHODS: A total number of 230 RB obtained from patients over 18 years of age, within the period from January 2009 to July 2013, were analyzed retrospectively. All RB were performed by a standartized technique using an automated spring fired biopsy gun, with 16, and 18 G disposable needle. The average age of the patients was 45.5 +/- 22.3 years, 119 male and 111 female. As many as 170 biopsies were performed with 16 G needle and 60 with 18G. The assessment of the early post-biopsy complications was done by renal ultrasound (US). RESULTS: Of all RB, 92.7% were successfully performed. In 60% of the failed RB 18 G needle was used. No post-biopsy complications were noted in 93.4%. Hematomas were observed in 15 out of 230 cases (6.6%). Of those, 80% were assessed as minor hematomas (12/15) with an average size of 20.4mm +/- 11mm and they appeared to be asymptomatic.While 8 cases (66%) of all 12 minor hematomas were obtained by two passes (66%), only 4 cases (34%) of hematoma were observed after one pass <0.01. The cases of hematomas obtained with 16 G needle were significantly higher than those in the group with 18G (8 to 4, p<0,05). However, when the number of hematomas in both groups referred to the number of all biopsies in the corresponding group, no significant difference of this complication was observed, p > 0.05. The incidence of major complications was 1.3%. CONCLUSION: The optimal period for US examination of the kidneys for early diagnosis of complications is up to 24 hours after RB. The experience of the physician performing the procedure is of great importance for reducing the risk of complications as well as the RB technique used. An automated spring fired biopsy gun with needle 16G is recommended. PMID- 25125952 TI - Postoperative analgesic effect of epidural neostigmine following caesarean section. AB - AIM: The aim of this study was to evaluate the analgesic effects of postoperative epidural administration of neostigmine and morphine in patients scheduled for caesarean section under epidural anaesthesia. MATERIAL AND METHODS: Sixty ASA I II patients, scheduled for caesarean section under epidural anaesthesia, were randomly allocated into three groups. Neostigmine (10 MUg/kg), morphine (3 mg), and saline (6 mL) were administered to the neostigmine, morphine, and control groups, respectively, 30 minutes after the surgery via the epidural catheter. Afterwards, postoperative pain treatment was administered to all patients with a patient-controlled epidural analgesia (PCEA) device, using 0.125% bupivacaine. The patients were followed up for 24 hours. The total volume of local anaesthetics used, the time to first analgesic requirement, analgesic requirements, VAS scores, analgesia quality, first passage of bowel gas, ambulation times, haemodynamic parameters and side effects were evaluated. RESULTS: The time to first analgesic requirement was significantly longer in the morphine group than in the neostigmine and control groups (p<0.01), and in the neostigmine group compared to the control group (p<0.05). The total local anaesthetic consumption and the number of bolus injections were significantly higher in the control group than in the other groups (p<0.01). The first passage of bowel gas occurred significantly sooner in the neostigmine group than in the morphine (p<0.01) and the control (p<0.05) groups. Itching frequency was significantly higher in the morphine group than in the other two groups (p<0.05). VAS scores were similar in the morphine and neostigmine groups. CONCLUSION: Postoperative single-dose epidural neostigmine reduced the 24-hour analgesic requirements but in the chosen doses presented an analgesic effect significantly lower than morphine. Hippokratia 2014; 18 (1): 44-48. PMID- 25125953 TI - Effects of methylene blue in acute lung injury induced by blunt chest trauma. AB - BACKGROUND: We studied whether methylene blue (MB) treatment blunts chest trauma induced lung injury in rats. MATERIAL AND METHODS: Forty male Sprague-Dawley rats, 200-300g, were used. The rats were divided into five groups (n=8): control, early contusion (EC), early contusion + methylene blue (2 mg/kg, EC+MB), late contusion (LC), and late contusion + methylene blue (2 mg/kg, LC+MB). RESULTS: Histopathological analysis showed increased hemorrhage, alveolar wall thickness, edema, and inflammatory cell infiltrates in the EC and LC rats, which decreased upon MB treatment. Immunohistochemical studies revealed that MB reduced activation of inducible nitric oxide synthase (iNOS) and the number of active terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. A significant increase was observed in the malondialdehyde (MDA) and nitric oxide (NO) levels in the EC group compared to the control group (p<0.05). In addition, a significant decrease was reported in the glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels (p<0.01), but no significant difference was observed in the catalase (CAT) levels among the groups. The MDA level was significantly higher in the LC group compared to the control group, whereas the GSH level was significantly lower compared to the control group. The NO level in the EC+MB group was significantly lower when compared to the NO level in the EC group (p<0.05). CONCLUSION: The present study provides evidence that MB might serve as a therapeutic treatment for blunt chest trauma. PMID- 25125955 TI - Cricotracheal separation with multiple cricoid fractures after blunt neck injury: a case report. AB - BACKGROUND/AIM: Cricotracheal separation is a rare injury with fatal results in most cases. Clear guidelines are not available and several dilemmas are to be faced during patient management in such cases. DESCRIPTION OF CASE: We present a case of cricotracheal separation with multiple cricoid fractures in a 16-year-old male with blunt neck trauma. CONCLUSION: Early recognition based on an index of clinical suspicion is necessary in order to establish this rare diagnosis. Intervention should preserve the laryngeal function as much as possible. PMID- 25125954 TI - Genotype 4 HCV infection is difficult to cure with pegylated interferon and ribavirin. Results from a Greek Nationwide Cohort Study. AB - BACKGROUND AND AIM: Patients with genotype 4 (G4) chronic hepatitis C (CHC) are considered a difficult to treat population, although current data on G4 treatment responsiveness and duration are controversial. Greece represents a country with an intermediate prevalence of G4 infections, offering an opportunity to compare treatment outcomes by genotype and to identify potential prognostic factors for sustained virologic response (SVR). METHODS: All CHC patients from the HepNet.Greece, an ongoing nationwide cohort study on viral hepatitis, with known hepatitis C virus (HCV) genotype who received treatment with Peg-IFNa and ribavirin were analyzed. RESULTS: From 4443 patients, 951 (61.7% males, 78.4% Greeks, median age 40.6 years, 10% cirrhosis) fulfilled the inclusion criteria. G4 was found in 125 (13.1%) patients. Genotype distribution was not significantly different between Greeks and immigrants. Patients with G4 had similar odds of SVR compared to G1 but significantly lower compared to G2/G3. Age, treatment discontinuation, presence of cirrhosis and previous history of HCV-treatment were associated with lower probabilities of SVR. Ethnicity did not affect SVR for all genotypes while response to treatment was similar between Greek and Egyptian patients groups (35.7% vs 40.9%, p=0.660%) with G4 infection. The relation between SVR and genotype did not substantially change after adjustment for age, gender, cirrhosis, treatment interruption and history of HCV-treatment. CONCLUSIONS: The findings of this large cohort of CHC patients with a well balanced genotype distribution further supports the idea of considering G4 as a difficult to treat genotype. Further investigation is needed to identify genotype specific prognostic factors. PMID- 25125956 TI - Systemic thrombolysis with the use of tenecteplase for segmental acute renal in farction potentially associated with multiple thrombophilic gene polymorphisms. AB - BACKGROUND/AIM: The potential association of acute renal infarction with multiple thrombophilic gene polymorphisms and the experience of treatment with tenecteplase are described for the first time in the international literature. DESCRIPTION OF THE CASE: The case of a 50-year old male with segmental acute renal infarction potentially associated with multiple thrombophilic gene polymorphisms is presented. He was thrombolysed with a single intravenous bolus of tenecteplase in a weight-adjusted dose (0.53mg/Kg bodyweight). Within 30 minutes after drug administration, the patient's symptoms were completely relieved. Patient's clinical course was uneventful with an acceptable renal function outcome eight weeks post-treatment. The following gene polymorphisms were identified: G455A (b-fibrinogen); C677T; A1298C (methylenetetrahydropholate reductase); T196C (platelet glycoprotein IIIa); 4G/5G (plasminogen activator inhibitor-1). CONCLUSION: Tenecteplase is a safe and simple to use thrombolytic, with favourable pharmacokinetic profile, which might be useful if administered early, especially when local thrombolysis is impossible or unavailable and therefore warrants further investigation in clinical trials. Hippokratia 2014; 18 (1): 67-70. PMID- 25125957 TI - A survival case of severe liver failure caused by acetylsalicylic acid that was treated with living donor liver transplantation. AB - BACKGROUND: Severe liver dysfunction caused by acetylsalicylic acid (ASA) is quite rare. The purpose is to describe a patient with severe liver dysfunction due to excessive intake of ASA in a suicide attempt, who was successfully treated with living donor liver transplantation (LDLT). DESCRIPTION OF CASE: We report a 20-year-old woman who took 66 g of ASA in a suicide attempt. She was admitted to our hospital and received forced alkaline diuresis. However, her liver and renal functions worsened after admission. On the 6th day after intake of ASA, she was transferred to the intensive care unit, and plasma exchange (PE) and continuous hemodiafiltration were performed. Since her liver function did not recover despite repeated PE, she was transferred to another hospital for LDLT on the 8th day. She underwent LDLT with a portion of the liver donated from her mother on the 11(th) day. After the operation, her renal dysfunction continued. Her renal parameters gradually improved, and she was discharged on the 44th post-operative day without renal dysfunction. CONCLUSION: PE is effective in removing ASA from blood. Liver transplantation is the only effective treatment if liver function does not recover in spite of repeated PE. PMID- 25125958 TI - Complicated acute appendicitis within a right inguinal hernia sac (Amyand's hernia): report of a case. AB - BACKGROUND: The term Amyand's hernia refers to a rare clinical situation characterized by the presence of a normal or inflammed appendix within the sac of an inguinal hernia. The situation may be asymptomatic or may present as an incarcerated hernia in case of strangulation or acute appendicitis occurring inside the hernia sac. DESCRIPTION OF THE CASE: We present the case of a right Amyand's hernia on a 88-years-old male that presented to our emergency department with a severely tender and swollen inguinal mass that was diagnosed as a strangulated inguinal hernia - inguinal abcess and underwent emergency operation. The intraoperative findings included a severely inflamed and perforated appendix along with healthy part of the caecum inside the sac. Appendectomy with subsequent primary hernia repair without mesh was performed with excellent outcome. CONCLUSION: Because of the fact that most of such rare cases are managed by urgent surgery with no preoperative diagnosis, every surgeon should be prepared for the possibility of coping with such an unexpected situation. PMID- 25125959 TI - A case of surgical instrument left in the abdomen and taken out of the transverse colon. AB - BACKGROUND: Foreign bodies cause an aseptic reaction that does not have specific symptoms and may also result in peritonitis, acute abdominal pain, an intraperitoneal abscess, or intestinal obstruction or perforation. We present a case of a surgical instrument left in the abdomen that passed into the transverse colon via migration after a surgery. CASE DESCRIPTION: A 36-year-old female patient was operated upon, with a diagnosis of a hydatid cyst in her liver. Approximately 3 years after the surgery, she excreted part of a surgical forceps with her stool while she was defecating. In upright direct abdominal radiography, a surgical instrument was observed in the abdomen. The patient was operated to remove the foreign body from the abdomen. The surgical instrument that was taken out had corroded and turned black. It was observed that the material that had dropped out of the anus and the material that was taken out during the operation were parts of the same surgical instrument. The ascending colon and the abdomen were stitched anatomically. Follow-ups were conducted after the operation, and the patient was discharged with recovery. CONCLUSIONS: It should be noted that a surgical instrument may be left inside the body of patients who have a history of surgery and that it can migrate. PMID- 25125960 TI - A case report of retroperitoneal extrahepatic hepatocellular carcinoma presented with elevated level of Alpha fetoprotein. AB - BACKGROUND: High level of alpha-fetoprotein is usually associated with testis cancer or hepatocellular carcinoma a primary tumor of the liver. CASE: We report the case of a 72-year-old male patient with chronic renal failure who presented with a high alpha-fetoprotein (AFP) level and a retroperitoneal mass, which was subsequently diagnosed to be an extrahepatic hepatocellular carcinoma. CONCLUSION: A retroperitoneal mass with elevated AFP level and no detected liver lesions is not always caused by a testicular cancer. PMID- 25125961 TI - Unusual histological patterns and hyaline ring granulomas in a unicystic ameloblastoma. AB - BACKGROUND: Unicystic ameloblastoma (UA) is a distinct variant of ameloblastoma displaying a large cystic cavity lining by ameloblastomatous epithelium and can present a wide variety of histologic patterns. CASE REPORT: We herein reported an unusual UA occurring in the mandible of a 23-year-old male patient who exhibited luminal, intraluminal and mural patterns, as well as acanthomatous, basal cells and granular cell variants. In addition, hyaline ring granulomas, an extraordinary finding in ameloblastoma, were found. The nature of several microscopic variants in this tumor and the possible significance of their presence have also been discussed. CONCLUSIONS: We believe this to be the first case reported in which a UA displayed multiplicity of histopathological patterns in a single lesion. PMID- 25125962 TI - De Quervain thyroiditis in the course of H1N1 influenza infection. AB - BACKGROUND/AIM: Viral infections have been frequently associated with subacute (De Quervain) thyroiditis and autoimmune thyroid diseases. In the present case report we document a rare case of De Quervain thyroiditis in the course of H1N1 influenza infection. DESCRIPTION OF THE CASE: A 17-year-old previously healthy female that was treated in the General Hospital of Kalamata developed an influenza-like syndrome that was accompanied by palpitations, thyroid enlargement, and increased C-reactive protein. Polymerase chain reaction assay confirmed the diagnosis of H1N1 virus infection. Serum thyroid-stimulating hormone was suppressed to zero while the levels of free thyroxine and triiodothyronine were increased. The patient was treated with non-steroidal anti inflammatory drugs and thyroid function was gradually restored without evolving to a hypothyroid phase. CONCLUSION: To our knowledge this is the second case described in the literature of De Quervain thyroiditis associated with H1N1 influenza infection. PMID- 25125963 TI - Cystic lymphangioma of the inguinal and scrotal regions in childhood - report of three cases. AB - BACKGROUND: [corrected] Cystic lymphangiomas are congenital lymphatic malformations that most commonly develop in the neck, axilla, mediastinum and retroperitoneum. Inguinal and scrotal lymphangiomas are extremely rare. CASES REPORT: We present the cases of three children with cystic lymphangiomas that were treated in our department during a two year period. The patients were all boys, aged 3.5, 9 and 13 years, and the location of the cystic lymphangioma was the scrotum, the inguinal region and the epididymis respectively. Clinical examination and ultrasonography described the lesions as cystic. Surgical excision of the lesions with a testis-sparing approach was performed in all three cases and histopathology set the diagnosis of cystic lymphangiomas. Complementary imaging of the regions adjacent to the excised lesions, excluded any extension or co-existing lesions. Post-operative period was uneventful and during a follow-up period of six months all patients were well with no signs of recurrence. CONCLUSIONS: Scrotal and inguinal cystic lymphangiomas are treated with surgical excision with care to preserve the intra-scrotal structures and the structures of the inguinal canal. Complete excision is necessary to prevent recurrence. Complementary imaging of the adjacent regions is necessary to identify any possible extension or co-existing lesions. PMID- 25125964 TI - Purple Urine Bag Syndrome: a case report of an alarming phenomenon. AB - BACKGROUND: Purple urine bag syndrome is an uncommon phenomenon where the plastic urinary catheter bag and tubing turn purple. It occurs in some elderly constipated chronic urinary catheterization patients. The phenomenon is attributed to the presence of metabolites of tryptophan in the presence of urinary tract infection.This urine discoloration may lead to misdiagnosis and also cause great concern to patients and their relatives. CASE REPORT: We present the clinical case of a 83-year-old female patient with dementia and hypothyroidism, chronically catheterized, who presented with purple-color urine initially misdiagnosed as having haematuria. PMID- 25125965 TI - Alpha heavy chain disease: a rare lymphoma hard to diagnose. PMID- 25125966 TI - Osteosarcoma in an adolescent previously treated for Hodgkin's Disease. PMID- 25125967 TI - An In-depth Analysis of a Multilocus Phylogeny Identifies leuS As a Reliable Phylogenetic Marker for the Genus Pantoea. AB - Partial sequences of six core genes (fusA, gyrB, leuS, pyrG, rlpB, and rpoB) of 37 strains of Pantoea species were analyzed in order to obtain a comprehensive view regarding the phylogenetic relationships within the Pantoea genus and compare tree topologies to identify gene(s) for reliable species and subspecies differentiation. All genes used in this study were effective at species-level delineation, but the internal nodes represented conflicting common ancestors in fusA- and pyrG-based phylogenies. Concatenated gene phylogeny gave the expected DNA relatedness, underscoring the significance of a multilocus sequence analysis. Pairwise comparison of topological distances and percent similarities indicated a significant differential influence of individual genes on the concatenated tree topology. leuS- and fusA-inferred phylogenies exhibited, respectively, the lowest (4) and highest (52) topological distances to the concatenated tree. These correlated well with high (96.3%) and low (64.4%) percent similarities of leuS- and fusA-inferred tree topologies to the concatenated tree, respectively. We conclude that the concatenated tree topology is strongly influenced by the gene with the highest number of polymorphic and non-synonymous sites in the absence of significant recombination events. PMID- 25125968 TI - iteRates: An R Package for Implementing a Parametric Rate Comparison on Phylogenetic Trees. AB - Patterns of diversification rate variation detected in phylogenetic hypotheses are frequently used to infer historical, ecological, and evolutionary processes. The parametric rate comparison (PRC) is a method for detecting rate variation in trees that models branch lengths as random variables drawn from familiar statistical distributions. iteRates is a library of functions for the R statistical computing environment for implementing PRC on phylogenetic trees. Here, we describe some of the functions in iteRates for subtree identification, tree manipulation, applying the PRC and K-clades PRC analyses, and conducting a whole-tree randomization test. PMID- 25125969 TI - Integrative Pathway Analysis Using Graph-Based Learning with Applications to TCGA Colon and Ovarian Data. AB - Recent method development has included multi-dimensional genomic data algorithms because such methods have more accurately predicted clinical phenotypes related to disease. This study is the first to conduct an integrative genomic pathway based analysis with a graph-based learning algorithm. The methodology of this analysis, graph-based semi-supervised learning, detects pathways that improve prediction of a dichotomous variable, which in this study is cancer stage. This analysis integrates genome-level gene expression, methylation, and single nucleotide polymorphism (SNP) data in serous cystadenocarcinoma (OV) and colon adenocarcinoma (COAD). The top 10 ranked predictive pathways in COAD and OV were biologically relevant to their respective cancer stages and significantly enhanced prediction accuracy and area under the ROC curve (AUC) when compared to single data-type analyses. This method is an effective way to simultaneously predict binary clinical phenotypes and discover their biological mechanisms. PMID- 25125970 TI - Hydroxyproline, a serum biomarker candidate for gastric ulcer in rats: a comparison study of metabolic analysis of gastric ulcer models induced by ethanol, stress, and aspirin. AB - Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce the serious side effect of gastric mucosal ulceration. Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy. We previously identified five metabolites as biomarker candidates for NSAID induced gastric ulcer using capillary electrophoresis-mass spectrometry (CE-MS) based metabolomic analysis of serum and stomach from rats. Here, to clarify mechanism of changes and limitations of indications of biomarker candidates, we performed CE-MS-based metabolomic profiling in stomach and serum from rats with gastric ulcers induced by ethanol, stress, and aspirin. The results suggest that a decrease in hydroxyproline reflects the induction of gastric injury and may be useful in identifying gastric ulcer induced by multiple causes. While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause. PMID- 25125971 TI - Molecular and Kinetic Characterization of Babesia microti Gray Strain Lactate Dehydrogenase as a Potential Drug Target. AB - Babesia microti is an emerging zoonotic protozoan organism that causes "malaria like" symptoms that can be fatal in immunocompromised people. Owing to lack of specific therapeutic regiment against the disease, we cloned and characterized B. microti lactate dehydrogenase (BmLDH) as a potential molecular drug receptor. The in vitro kinetic properties of BmLDH enzyme was evaluated using nicotinamide adenine dinucleotide (NAD(+)) as a co-factor and lactate as a substrate. Inhibitory assay was also done using gossypol as BmLDH inhibitor to determine the inhibitory concentration 50 (IC50). The result showed that the 0.99 kbp BmLDH gene codes for a barely soluble 36 kDa protein (332 amino acids) localized in both the cytoplasm and nucleus of the parasite. In vitro enzyme kinetic studies further revealed that BmLDH is an active enzyme with a high catalytic efficiency at optimal pH of 10.2. The K m values of NAD(+) and lactate were 8.7 +/- 0.57 mM and 99.9 +/- 22.33 mM, respectively. The IC50 value for gossypol was 0.345 MUM, while at 2.5 MUM, gossypol caused 100% inhibition of BmLDH catalytic activity. These findings, therefore, provide initial evidence that BmLDH could be a potential drug target, although further in vivo studies are needed to validate the practical application of lactate dehydrogenase inhibitors against B. microti infection. PMID- 25125972 TI - Memory Decline in Peri- and Post-menopausal Women: The Potential of Mind-Body Medicine to Improve Cognitive Performance. AB - Cognitive decline is a frequent complaint during the menopause transition and among post-menopausal women. Changes in memory correspond with diminished estrogen production. Further, many peri- and post-menopausal women report sleep concerns, depression, and hot flashes, and these factors may contribute to cognitive decline. Hormone therapy can increase estrogen but is contraindicated for many women. Mind-body medicine has been shown to have beneficial effects on sleep, mood, and hot flashes, among post-menopausal women. Further, mind-body medicine holds potential in addressing symptoms of cognitive decline post menopause. This study proposes an initial framework for how mind-body interventions may improve cognitive performance and inform future research seeking to identify the common and specific factors associated with mind-body medicine for addressing memory decline in peri- and post-menopausal women. It is our hope that this article will eventually lead to a more holistic and integrative approach to the treatment of cognitive deficits in peri- and post menopausal women. PMID- 25125973 TI - Subcutaneously administered methotrexate for rheumatoid arthritis, by prefilled syringes versus prefilled pens: patient preference and comparison of the self injection experience. AB - PURPOSE: This multicenter, randomized, crossover study compared preference, ease of use, acceptability, satisfaction, and safety of repeated subcutaneous (SC) self-administrations with prefilled pens and prefilled syringes delivering methotrexate (MTX), in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: The study (ClinicalTrials.gov number NCT01793259) enrolled 120 patients requiring initiation or intensification of MTX therapy for RA. Patients were randomized to receive the test drug, a prefilled pen (Metex((r)) PEN/Metoject((r)) PEN), or the reference drug, a prefilled syringe (Metex((r))/Metoject((r))), at doses of 15, 17.5, or 20 mg MTX SC once a week for 3 weeks. This was followed by receipt of the reference drug (prefilled syringe) or the test drug (prefilled pen) in a crossover design, with each patient serving as his/her own control. Questionnaires regarding patient preference, the Self Injection Assessment Questionnaire (SIAQ), and diaries regarding local tolerability were used to document outcomes. RESULTS: Overall patient preference for the MTX prefilled pen was 75% (P<0.0001). In a six-item questionnaire, 73% to 76% of the patients preferred the prefilled pen in relation to use, acceptability, and satisfaction, and 67% of the patients confirmed that it did not take much effort to overcome SC self-injection with the pen. The SIAQ showed no clinical differences, in any domain scores, between both devices. Overall patient attitude towards self-injection at baseline was positive, as was patient experience with both devices during the study. As well, 92% of physicians and study nurses indicated that they would recommend the MTX prefilled pen to patients for future MTX treatment. The formulations were generally well tolerated. CONCLUSION: SC self-injection of MTX with a prefilled pen was generally preferred, by patients with RA, over a prefilled syringe with regard to use, acceptability, and satisfaction. This is supported by the strong appreciation of their attending study nurses and physicians, for its convenience. PMID- 25125975 TI - Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo MetacoreTM software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process. PMID- 25125974 TI - Influence of diet and obesity on COPD development and outcomes. AB - The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern. Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest. Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases. Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and diet appear to play roles in its pathophysiology. Obesity has been associated with decreased lung-function measures in population-based studies, with increased prevalence of several lung diseases and with compromised pulmonary function. In contrast, obesity has a protective effect against mortality in severe chronic obstructive pulmonary disease (COPD). Nutrient intake and dietary patterns have also been associated with lung-function measures and the development and progression of COPD. Taken together, this suggests that a focus on obesity and diet should be part of public health campaigns to reduce the burden of lung disease, and could have important implications for clinicians in the management of their patients. Future research should also focus on elucidating these relationships in diverse populations and age-groups, and on understanding the complex interaction between behavior, environment, and genetics in the development and progression of COPD. The goal of this article is to review current evidence regarding the role that obesity and diet play in the development of COPD, and in COPD-related outcomes. PMID- 25125978 TI - Support for the initial attachment, growth and differentiation of MG-63 cells: a comparison between nano-size hydroxyapatite and micro-size hydroxyapatite in composites. AB - Hydroxyapatite (HA) is considered to be a bioactive material that favorably influences the adhesion, growth, and osteogenic differentiation of osteoblasts. To optimize the cell response on the hydroxyapatite composite, it is desirable to assess the optimum concentration and also the optimum particle size. The aim of our study was to prepare composite materials made of polydimethylsiloxane, polyamide, and nano-sized (N) or micro-sized (M) HA, with an HA content of 0%, 2%, 5%, 10%, 15%, 20%, 25% (v/v) (referred to as N0-N25 or M0-M25), and to evaluate them in vitro in cultures with human osteoblast-like MG-63 cells. For clinical applications, fast osseointegration of the implant into the bone is essential. We observed the greatest initial cell adhesion on composites M10 and N5. Nano-sized HA supported cell growth, especially during the first 3 days of culture. On composites with micro-size HA (2%-15%), MG-63 cells reached the highest densities on day 7. Samples M20 and M25, however, were toxic for MG-63 cells, although these composites supported the production of osteocalcin in these cells. On N2, a higher concentration of osteopontin was found in MG-63 cells. For biomedical applications, the concentration range of 5%-15% (v/v) nano-size or micro-size HA seems to be optimum. PMID- 25125979 TI - High-sensitivity C-reactive protein, lipoprotein-related phospholipase A2, and acute ischemic stroke. AB - BACKGROUND: Serum biomarkers may be useful for early diagnosis of acute ischemic stroke, exclusion of other diseases that may mimic stroke, and prediction of infarct volume. We evaluated serum high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-related phospholipase A2 (Lp-PLA2) in patients who had acute ischemic stroke. METHODS: In 200 patients who presented to an emergency service (acute ischemic stroke, 102 patients; control with no stroke, 98 patients), stroke patients were evaluated with the Canadian neurological scale and diffusion weighted magnetic resonance imaging, and all patients were evaluated with the Glasgow coma scale and their serum hs-CRP level and Lp-PLA2 activity were assessed. The volume of stroke lesions was calculated from magnetic resonance images. RESULTS: Patients who had stroke had higher mean serum hs-CRP level (stroke, 7+/-6 mg/dL; control, mean +/- standard deviation 1+/-1 mg/dL; P<=0.001) and Lp-PLA2 activity (stroke, mean +/- standard deviation 113+/-86 nmol/min/mL; control, mean +/- standard deviation 103+/-50 nmol/min/mL; P<=0.001) than control patients who did not have stroke. The mean hs-CRP level and Lp-PLA2 activity were higher in patients who had greater stroke severity (lower Canadian neurological scale score) and were higher in patients who had larger volume strokes. CONCLUSION: Higher hs-CRP level and Lp-PLA2 activity are significantly associated with more severe neurologic impairment and larger infarct size in patients who have acute ischemic stroke. These biomarkers may be useful for rapid diagnosis and prediction of ischemic tissue volume in the early stage of ischemic stroke. These findings may be important for health care facilities that have limited access to emergency computed tomography scanning for the diagnosis of stroke. PMID- 25125976 TI - Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a common and morbid disease characterized by high oxidative stress. Its pathogenesis is complex, and involves excessive oxidative stress (redox imbalance), protease/antiprotease imbalance, inflammation, apoptosis, and autoimmunity. Among these, oxidative stress has a pivotal role in the pathogenesis of COPD by initiating and mediating various redox-sensitive signal transduction pathways and gene expression. The protective physiological mechanisms of the redox balance in the human body, their role in the pathogenesis of COPD, and the clinical correlation between oxidative stress and COPD are reviewed in this paper. N-acetylcysteine (NAC) is a mucolytic agent with both antioxidant and anti-inflammatory properties. This paper also reviews the use of NAC in patients with COPD, especially the dose-dependent properties of NAC, eg, its effects on lung function and the exacerbation rate in patients with the disease. Earlier data from BRONCUS (the Bronchitis Randomized on NAC Cost Utility Study) did not suggest that NAC was beneficial in patients with COPD, only indicating that it reduced exacerbation in an "inhaled steroid-naive" subgroup. With regard to the dose-dependent properties of NAC, two recent randomized controlled Chinese trials suggested that high-dose NAC (1,200 mg daily) can reduce exacerbations in patients with COPD, especially in those with an earlier (moderately severe) stage of disease, and also in those who are at high risk of exacerbations. However, there was no significant effect on symptoms or quality of life in patients receiving NAC. Further studies are warranted to investigate the effect of NAC at higher doses in non-Chinese patients with COPD. PMID- 25125980 TI - Breast cancer characteristics and survival in a Hispanic population of costa rica. AB - BACKGROUND: Breast cancer characteristics may vary according to the patient's ethnic group. The goal of this cohort study was to evaluate the characteristics of a group of Costa Rican breast cancer patients and their relationship with survival. METHODS: Age, stage, tumor grade, immunohistochemistry, lymphovascular invasion, recurrence, and survival data on 199 Hispanic patients with breast cancer diagnosis, treated between January 2009 and May 2010, were collected from a single institution in San Jose, Costa Rica. The data were statistically analyzed for significance. RESULTS: Median age at diagnosis was 53 years. With a median follow-up of 46.5 months, there was an 88% overall survival rate. Thirty seven percent of the patients (p < 0.001) were at stages III and IV during diagnosis. The hormone receptor human epidermal receptor negative phenotype (HR HER2-) (p < 0.001) was present in 17% of the cases. In a multivariate analysis, local (risk ratio, RR: 7.2; confidence interval, CI 95%: 3.8-7.6; p = 0.06) and distant recurrence (RR: 14.9; CI 95%: 7.7-28.9; p = 0.01) showed the strongest association with the probability of death from the disease. Patients with HR-HER2 phenotype tumors reported more local recurrences (p = 0.04), a higher tumor grade (p < 0.01), and lower overall survival than patients with other breast cancer phenotypes (p = 0.01). CONCLUSIONS: Although this study analyzes a modest number of cases, it is an initial insight into factors that may contribute to differences in breast cancer outcomes among Hispanic women in Costa Rica. The higher proportion of triple negative tumors, advanced stage, and younger median age at diagnosis could contribute to the inferior prognostic described among Hispanic women. There may be a different distribution of tumor subtypes compared to non-Hispanic white women. Further studies are necessary to confirm such findings. PMID- 25125977 TI - Cellular trafficking and anticancer activity of Garcinia mangostana extract encapsulated polymeric nanoparticles. AB - Garcinia mangostana Linn extract (GME) is a natural product that has received considerable attention in cancer therapy, and has the potential to reduce side effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and encapsulation efficiency using a solvent-displacement method with particle sizes around 250 nm. Cellular uptake and accumulation of GME was higher for GME encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed approximately twofold-higher anticancer activity compared to GME-EC nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and trafficked through the endolysosomal pathway. As far as we know, this is the first report on the cellular uptake and intracellular trafficking mechanism of drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using cellulose-derivative nanoparticles - GME-EC and GME-EC/MC nanoparticles - successfully improved the bioavailability of GME in aqueous solution, enhanced cellular uptake, and displayed effective anticancer activity. PMID- 25125982 TI - Breast Positioning during Mammography: Mistakes to be Avoided. AB - AIMS AND OBJECTIVES: Breast positioning is the key factor affecting a mammogram. If care is taken during positioning, it maximizes the amount of breast tissue being imaged, eliminates most of the artifacts, and increases sensitivity of the mammogram. This retrospective study was carried out in our department to assess correctness, and also the incorrectness of breast positioning, which need to be avoided to obtain an ideal mammogram. MATERIAL AND METHODS: A total of 1369 female patients were included in this study. Mammography was performed on full field detector digital mammography equipment. Craniocaudal (CC) view and mediolateral oblique (MLO) view were carried out for each breast. Four views were done for 1322 patients. The remaining 47 patients had undergone a mastectomy and underwent two views for the other breast. Mistakes in improperly positioned mammogram were assessed with respect to proper visualization of nipple, position of pectoralis major, pectoral-nipple distance (PND), inframammary fold, and adequate coverage of all breast quadrants. RESULTS: As per prescribed guidelines, mistakes in positioning were recognized in 2.879% of total mammograms. Improper positioning of the nipple was the commonest problem, seen in 3.827% of mammograms, CC view. On MLO view, bilaterally, pectoralis shadow was not seen in 0.520% mammograms, its margin was not straight/convex in 0.706%, lower edge of pectoralis was above pectoralis-nipple line in 2.081%, and inframammary fold was not seen in 1.189%. There was inadequate coverage of lower quadrants in 2.787%, and mismatch in PND was seen in 3.864%. In few of the patients, the shortcomings as a result of improper positioning were noted on one view, the rest being normal. CONCLUSION: Positioning is the most important factor affecting the resultant mammography image. During mammography, many cases are improperly positioned and as a result the examination is inconclusive, which reduces the sensitivity of mammography. PMID- 25125981 TI - Current Approaches and Emerging Directions in HER2-resistant Breast Cancer. AB - Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall survival in adjuvant and first-line settings. However, a large proportion of patients with breast cancer have intrinsic resistance to HER2-targeted therapies, and nearly all become resistant to therapy after initial response. Elucidation of underlying mechanisms contributing to HER2 resistance has led to development of novel therapeutic strategies, including those targeting HER2 and downstream pathways, heat shock protein 90, telomerase, and vascular endothelial growth factor inhibitors. Numerous clinical trials are ongoing or completed, including phase 3 data for the mammalian target of rapamycin inhibitor everolimus in patients with HER2 resistant breast cancer. This review considers the molecular mechanisms associated with HER2 resistance and evaluates the evidence for use of evolving strategies in patients with HER2-resistant breast cancer. PMID- 25125983 TI - Improvement of quality and safety in health care as a new interprofessional learning module - evaluation from students. AB - BACKGROUND: Interprofessional teamwork is in many ways a norm in modern health care, and needs to be taught during professional education. DESCRIPTION: This study is an evaluation of a newly introduced and mandatory learning module where students from different health profession programs used Improvement of Quality and Safety as a way to develop interprofessional competence in a real-life setting. The intention of this learning module was to integrate interprofessional teamwork within the students' basic education, and to give students a basic knowledge about Improvement of Quality and Safety. This report focuses on evaluations from the participating students (n=222), mainly medical and nursing students. MATERIALS AND METHODS: To evaluate this new learning module, a questionnaire was developed and analyzed using a mixed methods design, integrating both qualitative and quantitative methods. The evaluation addressed learning concepts, learning objectives, and interprofessional and professional development. RESULTS AND CONCLUSION: A majority of students responded positively to the learning module as a whole, but many were negative towards specific parts of the learning module and its implementation. Medical students and male students were less positive towards this learning module. Improvements and alterations were suggested. PMID- 25125984 TI - Pediatricians' perceptions of clinical practice guidelines. AB - BACKGROUND: Clinical practice guidelines (CPGs) are propositions for health care providers about the care of patients and are usually described as "systematically developed statements to assist practitioners' and patients' decisions about appropriate health care for specific circumstances". OBJECTIVES: The purpose of this study was to investigate pediatricians' perceptions of clinical practice guidelines at Hamad Medical Corporation (HMC) in Qatar. METHODS: A cross sectional study was conducted at HMC between May 1 and August 31, 2013 using a self-administered questionnaire that was distributed to 240 pediatricians. RESULTS: A total of 169/240 questionnaires were completed for a response rate of 70.4%. Our main finding was that pediatricians at all levels are familiar with CPGs and use them. In addition, our doctors believe that CPGs lead to good quality of care, are practical, provide standardized patient care, will keep them up-to-date, decrease the rate of litigation, are evidence-based, do not restrict continuity of self-education, do not alter physician esteem, lead to improvement of outcome, and are practical. However, barriers that might impede pediatricians' use of CPGs are that CPGs affect their clinical judgment, do not match with their practice style, and do not reduce health care costs. CONCLUSIONS: Pediatricians at HMC have positive perceptions of CPGs. The results of our study suggest that CPGs are likely to be implemented if more counseling and education are provided to pediatricians regarding the usefulness of evidence-based guidelines. In addition, a program should be initialized to remove barriers while simultaneously addressing physicians' concerns. PMID- 25125987 TI - Use of frameless intrauterine devices and systems in young nulliparous and adolescent women: results of a multicenter study. AB - BACKGROUND: The purpose of this study was to provide additional data on the experience with frameless copper and levonorgestrel (LNG) intrauterine devices (IUDs) in nulliparous and adolescent women. METHODS: Nulliparous and adolescent women, 25 years of age or younger, using the frameless copper IUD or the frameless LNG-releasing intrauterine system (IUS), were selected from previous studies and a current multicenter post-marketing study with the frameless copper IUD. The small copper-releasing GyneFix((r)) 200 IUD consists of four copper cylinders, each 5 mm long and only 2.2 mm wide. The frameless FibroPlant((r)) LNG IUS consists of a fibrous delivery system releasing the hormone levonorgestrel (LNG-IUS). The main features of these intrauterine contraceptives are that they are frameless, flexible, and anchored to the fundus of the uterus. RESULTS: One hundred and fifty-four nulliparous and adolescent women participated in the combined study. One pregnancy occurred with the GyneFix 200 IUD after unnoticed early expulsion of the device (cumulative pregnancy rate 1.1 at one year). Two further expulsions were reported, one with the GyneFix 200 IUD and the other with the FibroPlant LNG-IUS. The cumulative expulsion rate at one year was 1.1 with the copper IUD and 2.2 with the LNG-IUS. The total discontinuation rate at one year was low (3.3 and 4.3 with the copper IUD and LNG-IUS, respectively) and resulted in a high rate of continuation of use at one year (96.7 with the copper IUD and 95.7 with the LNG-IUS, respectively). Continuation rates for both frameless copper IUD and frameless LNG-IUS remained high at 3 years (>90%). There were no cases of perforations or pelvic inflammatory disease reported during or following insertion. CONCLUSION: This report confirms earlier studies with frameless devices and suggests that the high user continuation rate is attributable to the optimal relationship between the IUD and the uterine cavity. IUD studies have shown that an IUD that does not fit well will often lead to side effects (ie, pain, bleeding, embedment, expulsion) and subsequent removal of the IUD. Early discontinuation is not the aim of long-acting reversible contraception. PMID- 25125986 TI - Hyperemesis gravidarum: current perspectives. AB - Hyperemesis gravidarum is a complex condition with a multifactorial etiology characterized by severe intractable nausea and vomiting. Despite a high prevalence, studies exploring underlying etiology and treatments are limited. We performed a literature review, focusing on articles published over the last 10 years, to examine current perspectives and recent developments in hyperemesis gravidarum. PMID- 25125988 TI - Incidence and risk of infection in egyptian patients with systemic lupus erythematosus. AB - BACKGROUND: Infection in systemic lupus erythematosus (SLE) is common and is one of the leading causes of morbidity and mortality. OBJECTIVE: To study the risk and occurrence of infection in Egyptian SLE patients and to determine its characteristics. METHODS: A total of 200 SLE patients were followed up for 1 year at monthly intervals, undergoing clinical and laboratory evaluation. Disease activity was assessed by SLE disease activity measurement (SLAM) score. Infections were diagnosed on basis of clinical findings, medical opinion, positive blood and urine cultures, Gram stain results, and specific serological assays as measurement of CMV and EBV antibodies. RESULTS: A total of 55% of patients developed infection, 45% had one infection, and the rest had multiple infection episodes. Total number of infections was 233 infections/year, 47.2% were major and 52.8% were minor infections. Urinary tract was the most commonly involved site with bacterial infection being the commonest isolated organism (46.4%), and E. coli the commonest isolated bacteria (14.2%). There were 51 episodes caused by systemic viral infection (CMV in 25, EBV in 22, HCV in 3, and 1 in HBV). CONCLUSION: There is a high rate of infection among SLE patients. Disease activity, leukopenia, high CRP level, positive anti-dsDNA, consumed C3, and cyclophosphamide therapy are independent risk factors for infection in SLE. PMID- 25125989 TI - Do we have to perform a renal biopsy? Clinical dilemmas in a case with nephrotic syndrome. AB - Renal biopsy is one of the pivotal diagnostic tools used in the field of nephrology. A morphological analysis of the kidney may also be of value for the overall management of patients with diabetic nephropathy. However, the indications for renal biopsy differ considerably among nephrologists, and no global consensus regarding performing this procedure among diabetic patients with various renal manifestations has yet been achieved. In this report, we would like to describe our serendipitous experience with a male type 2 diabetic patient presenting with nephrotic syndrome complicated by concurrent gastric carcinoma. We also discuss several conundrums that arose in the current case, which had an impact on our diagnostic and therapeutic decisions. PMID- 25125985 TI - Epidemiology of human African trypanosomiasis. AB - Human African trypanosomiasis (HAT), or sleeping sickness, is caused by Trypanosoma brucei gambiense, which is a chronic form of the disease present in western and central Africa, and by Trypanosoma brucei rhodesiense, which is an acute disease located in eastern and southern Africa. The rhodesiense form is a zoonosis, with the occasional infection of humans, but in the gambiense form, the human being is regarded as the main reservoir that plays a key role in the transmission cycle of the disease. The gambiense form currently assumes that 98% of the cases are declared; the Democratic Republic of the Congo is the most affected country, with more than 75% of the gambiense cases declared. The epidemiology of the disease is mediated by the interaction of the parasite (trypanosome) with the vectors (tsetse flies), as well as with the human and animal hosts within a particular environment. Related to these interactions, the disease is confined in spatially limited areas called "foci", which are located in Sub-Saharan Africa, mainly in remote rural areas. The risk of contracting HAT is, therefore, determined by the possibility of contact of a human being with an infected tsetse fly. Epidemics of HAT were described at the beginning of the 20th century; intensive activities have been set up to confront the disease, and it was under control in the 1960s, with fewer than 5,000 cases reported in the whole continent. The disease resurged at the end of the 1990s, but renewed efforts from endemic countries, cooperation agencies, and nongovernmental organizations led by the World Health Organization succeeded to raise awareness and resources, while reinforcing national programs, reversing the trend of the cases reported, and bringing the disease under control again. In this context, sustainable elimination of the gambiense HAT, defined as the interruption of the transmission of the disease, was considered as a feasible target for 2030. Since rhodesiense HAT is a zoonosis, where the animal reservoir plays a key role, the interruption of the disease's transmission is not deemed feasible. PMID- 25125990 TI - Schwannoma of the median nerve: diagnosis sometimes delayed. AB - Schwannoma is a tumor that develops from nerve sheath. The authors report an unusual case of schwannoma of the median nerve (MN) that remained asymptomatic for four years. The diagnosis was based on MRI (magnetic resonance imaging) and histopathological examination. Surgical removal is usually curative. The asymptomatic character of the tumor and its slow evolution remain an essential factor in diagnosis delays. This tumor has a good prognosis with a low recurrence rate and potential for malignant transformation. PMID- 25125993 TI - "When was the last tiame you do something for the first time" part 2. PMID- 25125991 TI - Age and menopausal status affect osteoprotegerin and osteocalcin levels in women differently, irrespective of thyroid function. AB - Osteoprotegerin (OPG) and osteocalcin (OC) are essential bone proteins. Recent studies have demonstrated that they are not secreted solely by bone cells; they play roles in the vascular function and energy metabolism, and they are influenced by multiple factors. The aim of the current study was to investigate the influence of menopause and age on OPG and OC in women with different thyroid stimulating hormone (TSH) levels. MATERIAL AND METHODS: We studied 49 women with elevated TSH, 26 with suppressed TSH, and 67 age-matched euthyroid controls. Of them 64 were menstruating and 78 postmenopausal. Body weight, height, waist circumference (WC), body mass index (BMI), serum TSH, free thyroxin (FT4), OPG, and OC were measured. RESULTS: Generally, both OPG and OC were higher in the postmenopausal women than in the menstruating subjects (OPG 3.85 +/- 1.49 pmol/L vs. 5.84 +/- 2.42 pmol/L, P < 0.001; OC 8.84 +/- 3.70 ng/dL vs. 12.87 +/- 6.45 ng/dL, P < 0.001), and within the two thyroid dysfunction subgroups and the controls (all P < 0.05). OPG correlated with age (postmenopausal rho = 0.57, P < 0.001; premenopausal rho = 0.31, P = 0.015). Among the premenopausal subjects, OPG was higher in those with low TSH than in the controls (P = 0.048). OC correlated negatively with BMI and WC in the postmenopausal group (Spearman rho = -0.25, P = 0.03 and rho = -0.42, P < 0.001 respectively). OC was higher in the postmenopausal subjects with low TSH than in those with elevated TSH (P = 0.024), and correlated positively with FT4 (rho = 0.40, P = 0.002) and negatively with TSH (rho = -0.29, P = 0.013). CONCLUSIONS: In women, OPG and OC depended differently on age and menopause and, to a lesser extent, on the thyroid function and body composition. PMID- 25125994 TI - Nuclear accident crisis and liver disease: a summary on evidences. AB - The present global concern is on the adverse effect due to exposure to nuclides expelled from the disrupted nuclear power plant accident in Japan. The exposure can induce several adverse effects. In this specific brief review, the author summarizes the evidences on the effect on liver. Discussion is focused on several liver diseases. PMID- 25125992 TI - Biomimetic electrospun nanofibrous structures for tissue engineering. AB - Biomimetic nanofibrous scaffolds mimicking important features of the native extracellular matrix provide a promising strategy to restore functions or achieve favorable responses for tissue regeneration. This review provides a brief overview of current state-of-the-art research designing and using biomimetic electrospun nanofibers as scaffolds for tissue engineering. It begins with a brief introduction of electrospinning and nanofibers, with a focus on issues related to the biomimetic design aspects. The review next focuses on several typical biomimetic nanofibrous structures (e.g. aligned, aligned to random, spiral, tubular, and sheath membrane) that have great potential for tissue engineering scaffolds, and describes their fabrication, advantages, and applications in tissue engineering. The review concludes with perspectives on challenges and future directions for design, fabrication, and utilization of scaffolds based on electrospun nanofibers. PMID- 25125995 TI - Tc-99m mebrofenin hepatobiliary scan in obstructive hepatobiliary disease: determining causes with early and late delayed imaging. AB - Hepatobiliary radionuclide imaging is typically performed to detect cholecystitis. Infrequently, imaging reveals an obstructive pattern. Although delayed hepatobiliary imaging is commonly used to differentiate between intrahepatic (IH) and extrahepatic (EH) obstruction in the newborn; there is room to clarify the use of delayed imaging in the adult population. A retrospective review was performed of adult patients demonstrating a complete obstructive pattern on initial Tc-99m mebrofenin hepatobiliary imaging. Delayed imaging was divided into early delayed (ED) (<10 h) and late delayed (LD) (>=10 h) imaging. Two physicians qualified the presence of intestinal radiotracer (negative, low to high) on delayed images. Determination of EH or IH pathology was obtained from chart review. A total of 24 patients demonstrated an obstructive pattern using delayed Tc-99m mebrofenin hepatobiliary imaging, with delayed imaging ranging from 4 to 30 h. EH pathologies (choledocholithiasis, stricture, other) represented 63% of cases (n = 15), IH pathologies (cirrhosis, hepatitis, other) represented 33% cases (n = 8) and 1 case was indeterminate. 67% of EH cases showed intestinal activity on delayed imaging (67% on ED and 67% on LD imaging), whereas 63% of IH cases showed intestinal activity on delayed imaging (67% on ED imaging and 60% on LD imaging). The presence of intestinal activity on the both the early and delayed images did not differentiate between the IH and EH pathology groups. Subdividing the groups into ED imaging and LD imaging was also not predictive of determining location of obstructive pattern on the initial 1 h of imaging. This data suggests that delayed hepatobiliary scintigraphy has little or no role in determining the cause of obstructive pathology. PMID- 25125996 TI - Factors predicting treatment failure in patients treated with iodine-131 for graves' disease. AB - Treatment of Graves' disease with iodine-131 ((131)I) is well-known; however, all patients do not respond to a single dose of (131)I and may require higher and repeated doses. This study was carried out to identify the factors, which can predict treatment failure to a single dose of (131)I treatment in these patients. Data of 150 patients with Graves' disease treated with 259-370 MBq of (131)I followed-up for at least 1-year were retrospectively analyzed. Logistic regression analysis was used to predict factors which can predict treatment failure, such as age, sex, duration of disease, grade of goiter, duration of treatment with anti-thyroid drugs, mean dosage of anti-thyroid drugs used, (99m)Tc-pertechnetate ((99m)TcO4 (-)) uptake at 20 min, dose of (131)I administered, total triiodothyronine and thyroxine levels. Of the 150 patients, 25 patients required retreatment within 1 year of initial treatment with (131)I. Logistic regression analysis revealed that male sex and (99m)TcO4 (-) uptake were associated with treatment failure. On receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) was significant for (99m)TcO4 (-) uptake predicting treatment failure (AUC = 0.623; P = 0.039). Optimum cutoff for (99m)TcO4 (-) uptake was 17.75 with a sensitivity of 68% and specificity of 66% to predict treatment failure. Patients with >17.75% (99m)TcO4 (-) uptake had odds ratio of 3.14 (P = 0.014) for treatment failure and male patients had odds ratio of 1.783 for treatment failure. Our results suggest that male patients and patients with high pre-treatment (99m)TcO4 (-) uptake are more likely to require repeated doses of (131)I to achieve complete remission. PMID- 25125997 TI - Empiric Therapy with Low-Dose I-131 in Differentiated Cancer Thyroid: What is the Magic Number? AB - Low dose radioactive iodine-131 (RAI) has been widely reported in the treatment of patients with differentiated thyroid cancer (DTC) since 1970's. However, the clinical outcomes, dosage of I-131 and criteria for successful ablation are different in various studies. The aim of this study was to assess clinical outcome 18-month after RAI therapy in selected DTC patients and identify factors associated with a good response. In this experimental study, among patients with DTC referred to the Nuclear Medicine Department and had an indication for RAI therapy in the period between December 2008 and January 2011, 108 subjects were selected randomly. The patients were randomly divided into three groups and empiric low dose therapy with 30, 50 or 75 mCi of I-131 was administered. Patients were monitored closely clinically and with serum thyroglobulin assays and I-131 whole-body scans at 6 monthly intervals for 18-month after treatment. Among 105 patients who completed follow-up, 86% were successfully ablated with a single low dose of I-131. There was no statistically significant difference in ablation rates in the subgroups receiving 30.50 or 75 mCi of I-131. Cumulative ablation rate was 99% in patients after the second dose of low dose therapy. If appropriate selection criteria are used in DTC, successful remnant ablation can be achieved with low doses of I-131 in the range of 30-75 mCi. No significant differences were found in results achieved with 30.50 or 75 mCi of I-131. As the majority of the DTC patients fall within the inclusion criteria of this study, they can be treated on an ambulatory basis with associated low cost, convenience, and low whole-body radiation-absorbed dose to the patients. PMID- 25125998 TI - Autonomous Functioning Thyroid Nodule in a 4-year-old Male Child Treated with Radioiodine (I-131). AB - Autonomous functioning thyroid nodules that cause toxic manifestations (toxic adenomas) are benign monoclonal tumors characterized by their capacity to grow and produce thyroxine (T4) and triiodothyronine (T3) autonomously, i.e. in the absence of thyrotropin thyroid stimulating hormone. Toxic adenomas are a rare presentation of hyperthyroidism in the pediatric population. Radioiodine (I-131) has been widely used for therapy of patients with toxic adenomas and is now accepted as a safe and effective treatment even in the pediatric age group. The authors here present a case of a 4-year-old boy with a solitary hyperfunctioning thyroid nodule, who was successfully treated with radioiodine (I-131) and is presently on follow-up. PMID- 25125999 TI - F-18 fluorodeoxyglucose positron emission tomography/computed tomography in the staging of linitis plastica caused by primary gastric adenocarcinoma. AB - Diffuse infiltration by a primary or metastatic malignancy into the submucosa and muscularis of the stomach (linitis plastica [LP]) has been described in literature. The authors present a case of LP caused by primary adenocarcinoma of the stomach, showing diffuse Fluorine-18 fluorodeoxyglucose uptake in the thickened wall of the stomach. PMID- 25126000 TI - Vesicoureteral Reflux Detected on Post-void Image of (99m)Tc MAG3 Renal Scintigraphy. AB - (99m)Tc MAG3 scintigraphic scan is sensitive at depicting focal parenchymal abnormalities and can be used for the measurement of overall renal function. We experienced a 5-year-old boy presenting with bilateral flank fain, intermittent urinary stream and dysuria. On the post-void delayed image of (99m)Tc MAG3 scintigraphic scan vesicoureteral reflux was detected in left non-functioning kidney, which was missed on voiding cystourethrography. PMID- 25126002 TI - False-positive (111)In-pentetreotide Uptake in Gastritis. AB - (111)In-pentetreotide [(111)In-octreoscan] is the most widely used radiolabeled somatostatin analog for evaluating neuroendocrine tumor overexpression of somatostatin receptors. False-positives studies of somatostatin receptor scintigraphy have been reported and often the cause is unexplained but assumed to be due to high number of somatostatin receptors in other pathologies. Causes of false-positives include visualization of the gallbladder, nasal mucosa and pulmonary hilar areas in respiratory infections, thyroid abnormalities, accessory spleens, recent Cerebrovascular accidents (CVA's) and activity at the site of a recent surgical incision. In infection or inflammation the cause of false positive uptake is probably the result of tracer binding by somatostatin receptors on the inflammatory leukocytes. In this case report, we report, a 44 year-old male patient with false-positive (111)In-pentetreotide uptake due to gastritis. PMID- 25126003 TI - Routine whole volume single photon emission tomography reconstruction in comparison to cine raw data in the detection of extracardiac uptake. PMID- 25126001 TI - Bone scanning in the adductor insertion avulsion syndrome. AB - A thigh splint (adductor insertion avulsion syndrome) is a relatively uncommon diagnosis analogous to shin splints. This article reports a 19-year-old female patient NOT a regular athlete who presented with groin pain. Physical examination was non-specific; magnetic resonance imaging pelvis did not reveal any abnormality. Patient referred for whole body bone scan, especially to locate any abnormality in the spine. This study highlights the role of whole body bone scan in the evaluation of groin pain and importance of evaluation of whole lower extremity. PMID- 25126004 TI - The role of plasma gelsolin in cardiopulmonary bypass induced acute lung injury in infants and young children: a pilot study. AB - BACKGROUND: Acute lung injury (ALI) induced by cardiopulmonary bypass (CPB, CPB ALI) is a common and serious complication after cardiac surgery. And infants and young children are more prone to CPB-ALI. The purpose of this study was to investigate the perioperative changes of plasma gelsolin (pGSN) in patients below 3 years of age with cardiac surgeries and CPB, and determine whether pGSN are associated with the occurrence and severity of CPB-ALI. METHODS: Seventy-seven consecutive patients <=3 years of age with congenital heart diseases (CHD) performed on open heart surgery with CPB were finally enrolled, and assigned to ALI and non-ALI groups according to the American-European Consensus Criteria. Plasma concentrations of gelsolin and total protein were measured at following 8 time points: before CPB (a), after CPB (b), 2 hours after CPB (c), 6 hours after CPB (d), 12 hours after CPB (e), 24 hours after CPB (f), 48 hours after CPB (g) and 72 hours after CPB (h). RESULTS: Twenty-seven (35.1%) patients developed CPB ALI in the study, including eleven (14.3%) patients with ARDS. The earliest significant drop of pGSN and normalized pGSN (pGSNN) of ALI group both occurred at 6 hours after CPB (p = 0.04 and p < 0.01), which was much earlier than those of non-ALI group (48 hours, p = 0.03 and 24 hours, p < 0.01); PGSN of ALI group before CPB and 6 hours after CPB were both significantly lower than those of non ALI group (p < 0.01); PGSNN of ALI group before CPB and 6 hours after CPB were both significantly lower than those of non-ALI group (p < 0.01, p = 0.04); PGSN before CPB was the only independent risk factor predicting the occurrence of CPB ALI (OR, 1.023; 95% CI, 1.007-1.039; p < 0.01) with an AUC of 0.753 (95% CI, 0.626-0.880); The optimal cutoff value of pGSN before CPB was 264.2 mg/L, with a sensitivity of 58.3% and a specificity 94.7%. And lower pGSN before CPB was significantly associated with the severity of CS-AKI (r = -0.45, p < 0.01). CONCLUSIONS: Patients developing CPB-ALI had lower plasma gelsolin reservoir and a much more amount and rapid consumption of plasma gelsolin early after operation. PGSN before CPB was an early and sensitive predictor of CPB-ALI in infants and young children undergoing cardiac surgery, and was negatively correlated with the severity of CPB-ALI. PMID- 25126006 TI - Combined hysterolaparoscopy for the diagnosis of female infertility: a retrospective study of 132 patients in china. AB - OBJECTIVES: To evaluate the effects and safeness of combined hysterolaparoscopy on evaluation the causes of infertility. METHODS: This retrospective study was conducted at the Department of Gynecology (The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China) from January 2011 to April 2014. Patients aged 21-43 years with infertility were included in this study. The prevalence of different lesions was collected to analyze. RESULTS: 132 infertile patients were included, 71 (53.8%) women had primary infertility and the rest 61 (46.2%) had secondary infertility. Laparoscopic abnormalites were more common than hysteroscopy abnormalites both in primary infertility group and secondary infertility group. Pelvic inflammatory disease (59.09 %) and endometriosis (29.55%) were the most common abnormalities in two groups. The most common intrauterine pathology was uterine polyps and the most common uterine malformation was uterine septum in two groups. Out of 12 patients having malformation uterus, only one was double uterus and double cervical with double vagina. There was no major surgical or anesthetic complication in any of our patients, other than mild abdominal pain. CONCLUSION: Hysterolaparoscopy is an effective and safe tool in comprehensive evaluation of infertility to diagnosis and treat the lesions of pelvic and uterus in the same time. Hysterolaparoscopy may be recommended as the first and final procedure for evaluation of female infertility. PMID- 25126007 TI - Prevalence and factors associated with congenital malformations in tirana, Albania, during 2011-2013. AB - AIM: Congenital Malformations (CMs) represent a challenge especially for developing countries. Data about CMs in Albania are rather scarce. In this context, our aim was to assess the prevalence and factors associated with CMs in Tirana, the capital of Albania. METHODS: Information on all CMs at birth during 2011-2013 was retrieved from the National CM Surveillance System. For each CM case, three controls (babies born without CM) were retrieved as well. Overall, 831 cases and 2522 controls were included in this study. The prevalence was calculated using the total number of live births in Tirana during the same period. Binary logistic regression was used to determine the factors associated with CMs adjusting for a number of covariates. RESULTS: The three-year prevalence of CMs was 23.41 per 1,000 live births. The most affected body systems were the musculoskeletal, cardiovascular and genital systems. CMs were more prevalent among male babies. Advanced mothers' age, lower education, unemployment status and lower gestational age were all positively associated with increased likelihood of CMs. CONCLUSIONS: Socio-demographic factors of mothers are linked to CMs in Albania. Future surveys are needed in Albania in order to establish determinants of CMs at a national level. PMID- 25126005 TI - Challenging dedifferentiated liposarcoma identified by MDM2-amplification, a report of two cases. AB - BACKGROUND: Liposarcoma is the most frequent soft tissue sarcoma. Well differentiated liposarcoma may progress into dedifferentiated liposarcoma with pleomorphic histology. A minority additionally features myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of the Mouse double minute 2 homolog (MDM2) locus is characteristic for well differentiated and dedifferentiated liposarcomas. Detection of MDM2 amplification may supplement histopathology and aid to distinguish liposarcoma from other soft tissue neoplasia. CASE PRESENTATION: Here we present two cases of dedifferentiated liposarcoma with challenging presentation. Case 1 features a myogenic component. As the tumour infiltrated the abdominal muscles and showed immunohistochemical expression of myogenic proteins, rhabdomyosarcoma had to be ruled out. Case 2 has an osteosarcomatous component resembling extraosseous osteosarcoma. The MDM2 status was determined in both cases and helped making the correct diagnosis. Overexpression of MDM2 and co-overexpression of Cyclin dependent kinase 4 is demonstrated by immunohistochemistry. The underlying MDM2 amplification is shown by fluorescence in situ hybridisation. Since low grade osteosarcoma may also harbour MDM2 amplification it is emphasised that the amplification has to be present in the lipomatous parts of the tumour to distinguish liposarcoma from extraosseous osteosarcoma. CONCLUSIONS: The two cases exemplify challenges in the diagnoses of dedifferentiated liposarcoma. Liposarcoma often has pleomorphic histology and additionally may feature heterologous components that mimic other soft tissue neoplasms. Amplification of MDM2 is characteristic for well differentiated and dedifferentiated liposarcomas. Determination of the MDM2 status by in situ hybridisation may assist histopathology and help to rule out differential diagnoses. PMID- 25126008 TI - The Role of CT Angiography of Coronaries in Early Diagnosis of Coronary Artery Plaques in Albanian People with No History of Cardiovascular Disease in Correlation with Traditional Risk Factors. AB - OBJECTIVE: To evaluate the role of CT angiography of coronaries (CTAC) in the diagnosis of subclinical atherosclerosis by detection of coronary artery plaques (CAP) in a group of consecutive albanian individuals with no history of coronary artery disease (CAD) or acute coronary syndrome and to investigate the relation between the prevalence of CAP, traditional risk factors and the expected 10-year risk of fatal cardiovascular event (CVE) based on our own experience. METHOD AND TECHNIQUE: This is a prospective study including 456 patients with no history of CAD who underwent CTAC in our hospital from September 2009 to March 2013. Risk estimation of fatal CVE was assessed using Systematic Coronary Risk Evaluation (SCORE) and then CT scan was performed with a 64 detector CT, including Ca Score and angiography of coronaries with iv contrast. RESULTS: From 456 patients 61.4% were low risk and 32.9% were at intermediate risk according to SCORE. The prevalence of CAP diagnosed by CTAC was calculated as 55.7 % overall. Though the presence and severity of CAP increased significantly with the increase of SCORE, it was found to be 44.1% in the low risk patients and 80% in the intermediate risk group, with a presence of 17% and 25% of stenotic plaques (>50%) respectively. Significant correlation was found between all traditional risk factors and CAP. CONCLUSION: Although a direct relation between the prevalence of CAP, risk factors and the related 10-year risk of fatal CVE was found, there was a significant prevalence of CAP in low -intermediate risk group with a considerable presence of stenotic lesions. Also 8.3% of patients with no risk factors and 18% of the patients with Ca score 0 had CAP in CT angiography, one resulting with severe stenosis. Our results suggest once more that CT angiography is a reliable, very accurate noninvasive technique for the diagnosis of early CAD, especially in the low-intermediate risk patients compared to the traditional evaluation schemes and Ca score, thus should be considered in this group as a diagnostic guide for optimal therapy planning. PMID- 25126009 TI - An epidemiological study on trigger factors and quality of life in psoriatic patients. AB - OBJECTIVE: to evaluate the role of stress, tobacco, drugs, infections, allergies, heredity, alcohol, hormones and skin aggressions as trigger factors and the impact on quality of life in a sample of psoriasis patients. METHODS: a transversal study performed in 90 patients affected by psoriasis between January and November 2012 at the "Nene Tereza" University Hospital, Tirane, Albania, based on two scored questionnaires. RESULTS: more than 70 % of patients reported that stressful events caused a flare- up of their psoriasis (p< 0.05). More than 60% of males and 20% of females were smokers (p< 0.05). About 20% of our patients were taking one or more of the medications listed in the questionnaire (p> 0.05). About 20% of patients reported having had recurrent infections (p<0,05). About 80% of males patients consumed alcohol (p<0,05). More than 40% reported a relative with psoriasis. Statistical comparison of the group that reported skin aggressions with the group that did not revealed a significant difference (p<0,05). Only a few of them reported to have allergies (p>0,05). About 36% of females reported that hormonal changes (puberty and menopause) exacerbated their psoriasis (p<0,05). More than 40% of patients reported that psoriasis seriously affects their quality of life. CONCLUSION: stress, tobacco, infections, heredity, alcohol, hormonal changes and skin aggressions were confirmed as trigger factors for psoriasis in the present sample. Allergies and the investigated drugs seemed not to have any influence in flare-ups. We found that psoriasis had a serious impact in the quality of life in over of 40% of the patients interviewed. PMID- 25126011 TI - Spatial analysis and geographic variation of fatal and injury crashes in mazandaran province from 2006 to 2010. AB - BACKGROUND: Road safety and traffic accidents change in time and space. Although, time variations have always been considered the subject being focused by researchers, the effect of spatial correlation and spatial components on the risk of accident have been less investigated. Due to its specific geographical position, Mazandaran Province is one of the highest traffic provinces. This study aims to investigate the factors influencing suburban crashes of Mazandaran province by considering the spatial correlation. METHODS: This study is aggregated (descriptive -analytical) and the study period was 2006 to 2010. Social and environmental factors effects on the risk of accidents have been studied considering the correlation structure of the regions and regardless of this structure with Poisson regression, negative binomial and Full Bayes hierarchical models. Geographical pattern of risk distribution for the observed values of SMRs and the estimated values after smoothing have been plotted and analyzed. RESULTS: Comparing the measures of models goodness of fit indicates that hierarchical Bayes model fits the data better. Plotting the geographical pattern, the north central parts of the province have been identified as the high risk areas. Human factors were identified as the important factors for the risk of accident. CONCLUSIONS: The purpose of this procedure is to separate the random effect of residuals correlation. Using this method, the measure of the model goodness of fit got reduced reflecting a better model than the prototype model. The significance of the structured spatial effect shows the existence of unknown explanatory variables with correlated structure whose identification and control can reduce the risk of accidents. PMID- 25126010 TI - Analysis of effect of antiviral therapy on regression of liver fibrosis in patient with HCV infection. AB - BACKGROUND: HCV infection is characterized by a tendency towards chronicity. Acute HCV infection progresses to chronic infection in 70% of cases. Hepatitis C virus infection can cause progressive liver injury and lead to fibrosis and eventually cirrhosis. The degree of histologic fibrosis is an important marker of the stage of the disease. One of current standard treatment for CHC infection is the combination of PEG-IFN alpha and ribavirin. OBJECTIVES: The aim of the study was to investigate the effect of the therapy with Peginterferon alfa-2a or alfa 2b plus Ribavirin on evolution of liver fibrosis in patients with chronic hepatitis C. Also, our aim was to examine whether there was a difference between the genders in the efficacy of these antiviral therapy. Our goal also was to determine effect of the therapy with Peginterferon alfa-2a or alfa-2b plus Ribavirin on evolution of liver steatosis in patients with chronic hepatitis C. PATIENTS AND METHODS: A retrospective study was made of chronic hepatitis C patients who had been treated from 2005 to April 2014 at the Clinic of Gastroenterohepatology, Clinical Center University of Sarajevo. We reviewed 40 patient medical records to collect demographic, epidemiological and clinical information, as information on liver biopsies that was performed prior to the antiviral therapy and FibroScan((r)) test that was performed after the antiviral therapy. For the processing of data SPSS (Statistical Package for the Social Sciences Program) for Windows, ver. 21.0 statistical software was used. Comparisons between qualitative and quantitative variables were performed using the Student t-test. Mann Whitney U test was used to compare differences in variables such as fibrosis stage and steatosis grade. A value of p<0.05 was considered as statistically significant. RESULTS: After treatment, there was a statistically significant increase in the number of patients with no fibrosis (p<0.05). There was no statistically significant reduction in the number of patients with cirrhosis (F4) (p>0.05). There was significantly higher decrease of fibrosis progression at the patients that were in an mild-to-moderate fibrosis (F1/F2/F3), patients that were in advanced stage of fibrosis (F4) at the time of the pre-treatment did not have a statistically significant fibrosis reduction. We found significant association in evolution of fibrosis after treatment with PEG IFN alpha2a (40) kD and PEG-IFNalpha2a (12,5) kD with ribavirin (p< 0.05). We also found significant association in evolution of steatosis after treatment with PEG-IFN alpha2a (40) kD and PEG-IFNalpha2a (12,5) kD with ribavirin (p < 0.05). There was statistically significant differences (p<0.05) between genders within fibrosis qualitative evolution. CONCLUSIONS: There were significant regression of fibrosis especially at the patients that were in an mild-to-moderate fibrosis (F1/F2/F3), patients that were in advanced stage of fibrosis (F4) at the time of the pre-treatment did not have a statistically significant fibrosis reduction after treatment with PEG-IFN alpha2a (40) kD and PEG-IFNalpha2b (12,5) kD with ribavirin. Our results showed significant improvement in steatosis in patients infected with HCV after treatment with PEG-IFN alpha2a (40) kD and PEG-IFNalpha2b (12,5) kD with ribavirin. Those results provides further evidence for direct involvement of HCV and antiviral therapy in the pathogenesis of hepatic steatosis. Female gender showed a higher degree of fibrosis reduction. PMID- 25126012 TI - A Cross-sectional Study of Midwives' Perspectives Towards their Professional Educational Needs. AB - BACKGROUND: Midwives are one of the most important health care providers and meeting their professional educational needs can be effective in maternal and child health promotion. AIM: The aim of this study was to investigate the midwives' perspectives towards their educational needs. METHODS: In this cross sectional study which was conducted in 2012 in Sari, North of Iran, 223 midwives during a convenience sampling method expressed their educational needs. The instrument of the data collection was a self-administered 64-question researcher- made questionnaire about the participants' educational needs in 10 fields related to midwifery profession. RESULTS: The mean age and employment record of the participants were 33.87+/-10.49 and 10.09+/-8.14 years respectively, and the majority (65.02%) of them was employed in the health care centers. Findings showed that the highest score of midwives' educational need was related to need to education about labor and delivery care (75.14+/-21.13%) which was followed by the need to education about pre marriage counseling (74.04+/-19.95%) and pre conception counseling (71.33+/-21.89%). CONCLUSIONS: Owing to the emergence of new dimensions of tasks in midwifery practice and due to developing some changes in the educational needs of midwives, it's necessary to implement an updated educational package in order to deliver the recommended standards of care and to increase midwives' participation in continuing education programs. PMID- 25126013 TI - Effect of cigarette smoking in pregnancy on infants anthropometric characteristics. AB - AIM: The main goal of this research is to correlate anthropometric characteristics of newborns in pregnant women who consume cigarettes during pregnancy. The study was conducted at the Obstetrics Clinic of the Clinical Center, University of Sarajevo. METHODS: The retrospective study covered a period of two years. Main inclusion criteria for the study was that pregnant women consume cigarettes during pregnancy. The research included respondents who had a singleton pregnancy, without pathological conditions that can affect the outcome and duration of pregnancy. RESULTS: At the Obstetrics Clinic, Clinical Center University of Sarajevo in the period from January 1, 2012 to December 31, 2013. In that period 393 pregnant women completed labor who in the personal history had data on smoking during pregnancy. Of the total number of subjects enrolled in this study 38.17% smoked up to 10 cigarettes a day, 33.08 % smoked up to 20 cigarettes a day, while up to 30 cigarettes per day smoked 28.75 % of respondents. CONCLUSION: There was a significant difference in the average values of all anthropometric parameters, in relation to the number of cigarettes consumed by the subjects during the day. We also found negative correlation in the average values of anthropometric measures and the number of cigarettes consumed (p <0.05). PMID- 25126014 TI - Rates and Indicators for Episiotomy in Modern Obstetrics - a study from Saudi Arabia. AB - BACKGROUND: This observational study aimed to describe the rates and indicators for practice of episiotomy during normal labour and to compare them between women who have had one pregnancy (PG) and women who have already delivered two or more children (G2 and above). METHODS: The study was conducted at Mother and Child Hospital, Buraidah from October- December 2013 as a descriptive cross sectional study. RESULTS: Overall rate of Episiotomy was 51.20%. Amongst the Primigravidas all went through episiotomies however in G2 and above only 7 patients (4.69%) delivered with episiotomy. Proportions tests revealed that there were significant differences between gravidity groups on two indications of episiotomy (vaginal breech p <0.001 and previous history of perineal tear p < 0.001). G2 and above had episiotomy for breech delivery (1 of 7 = 14.29%) significantly more often than PG participants (0 of 142 = 0.0%). And G2 and above participants experienced episiotomy for previous perineal tear (2 of 7 = 28.5% as compared to none in PG No other significant differences were found on indications of episiotomy. CONCLUSION: Episiotomy is a very common obstetric intervention (51.20%). The PG experience episiotomy significantly more often than G2 and above women. Efforts should be made to reduce its rates. This can be done by reviewing the indications and rates at repeated intervals and setting guidelines for these indications. PMID- 25126016 TI - Situational analysis of human resources in family physician program: survey from iran. AB - INTRODUCTION: Family physician is the increasing efforts to promote physician and other human resources in the health care systems. GOAL: Investigate Human resources situation of the family physician program in six pilot cities in Khuzestan province in the southwest of Iran. METHODS: A cross-sectional descriptive study was conducted to examine the family physician program in 2011. In this study, 15 healthcare teams in six pilot cities in Iran were assessed. Data was compiled from family physician officer document in vice treatment of Ahwaz University of medical sciences. National instructions of family physician was used to identify current gaps. RESULTS: The survey findings indicated that there is a doctor's shortage about 36% in the health team that deployed in the first level of referral system. Also on the team, the 34% shortage of nurses and 60% shortages of nutrition personnel are seen. Specialists with offices in cities of second referral level, there have not welcomed the program. CONCLUSIONS: It seems that to facilitate patient access to physicians under contract with family physician program and the referral system in level two and level three, adopting arrangements to attract specialists and improving their maintenance is necessary. PMID- 25126017 TI - Siege of town and establishment of field hospital. AB - INTRODUCTION: The degree of material and social development determines the basic characteristics of warfare. There are various causes, means and goals of warfare. From the standpoint of international war law, significant is the division between international and non-international (civil) war. International law of war is a part of public international law and constitutes a set of contractual and legal rules governing the relations between the international recognized subjects in times of armed conflict. The town of Konjic and Konjic municipalities are geographically located in the northern part of Herzegovina-Neretva Canton. It is the largest urban municipality in the state of Bosnia and Herzegovina. Distance to some settlements in the northeast to the northwest or the villages are 186 km. Municipality area is 1,101 km(2). According to the character of the mountainous districts, inhabited by a sparse population, which amounts to 29.65 people per 1 km(2). A third of the population lives in the city and suburbs, and the other two thirds is the rural population. GOAL: Our aim was to show that in an environment, space, under the conditions imposed suddenly by all sorts of war blockade, the successful in transformation from peacetime to war organization, with full support to local personnel and material-technical resources can be achieved successful results. MATERIAL AND METHODS: This research was conducted as a clinical, descriptive and retrospective, by valid documentation of War Hospital and already published thesis on a series of conferences, symposia and seminars at home and abroad. In this paper we show our results achieved in the care and treatment of injured and sick hospitalized in the War Hospital Konjic for the period from April 1992 till December 1995. RESULTS AND DISCUSSION: Of the total number of hospitalized at the surgical ward, 62% had an injury, a disease had 30.7%. Dominated by war injuries (78.9%). The total mortality in the surgical ward was 4.5%. By localization were most often represented injuries of the extremities (52.1%), followed by chest (22.4%), stomach (13.4%), head and neck (12.1%), and multiple wounds (10.4%). In case of extremity injury in 64% of cases it was a case of fracture of the bone and the skeleton, and 19.5% had an injury of the neuro-vascular structures. In case of injuries to the abdomen, usually it was a case of open injury (95%). CONCLUSION: War Hospital, in many cases of illness and injury, due to the proximity of combat operations, and all manner of constant blockade, uniting all four echelons of health care by war-surgical doctrine. Start the application of the doctrine of original beginning of the admission, triage departments and ending at the other hospital departments with definitive cure in 90% of cases. In the meantime, patients went through all the stages (diagnosis, resuscitation, surgical treatment, conservative treatment, isolation, etc.). PMID- 25126015 TI - Perception of Societal Stigma and Discrimination Towards People Living with HIV/AIDS in Lagos, Nigeria: a Qualitative Study. AB - INTRODUCTION: The perception of People Living with HIV/AIDS (PLWHAs) on how the public feels about them could influence their willingness to seek medical care, interaction with the society and their coping strategies. MATERIAL AND METHODS: This study assessed the perception and behavior of PLWHAs towards societal stigma and discrimination in Lagos, Nigeria. This was a qualitative, descriptive cross sectional study among PLWHAs from three of the three senatorial districts in Lagos State selected using simple random sampling. Six focus group discussions (FGDs), consisting of eight eligible respondents each were held using structured FGD guide. RESULTS: Collected data were analyzed using simple content analysis. About three quarter of all the discussants said life had become miserable following episodes of stigma and discrimination against their personality in public, family, health care settings and the work-place. Some had feelings of guilt and depression towards these actions. About three quarter had coped with the situation by living a low-keyed lifestyle, dissociating themselves from the public and avoiding seeking care in HIV care centers. Majority of respondents were not willing to come out to publicly discuss their positive HIV status for fear of discrimination. CONCLUSION: Discussants recommended continuous awareness campaigns about HIV to further educate the general public towards reduction of societal stigma and discrimination against PLWHAs. PMID- 25126018 TI - Studying the rate and causes of discharge against medical advice in hospitals affiliated to mazandaran university of medical sciences. AB - INTRODUCTION: Discharge against medical advice from the hospital is an important issue from point of view of treatment management, health costs as well as the side effects of treatment stop on patients and their accompanying. Therefore, health managers and planners should consider the predisposing factors that change patient's mind in this regard. Since, there has been no study to carefully assess the rate and causes of self-discharge in this province, so this study is aimed to fill this gap. METHODS AND MATERIALS: This descriptive and cross-sectional study was carried out in 6 months period, from 23 July 2010 till 20 January 2011 in all public hospitals of Mazandaran province. A form was set out for data collection and those patients willing to self-discharge were asked to participate in the study. Patients' demographic information was filled using their medical record and by the help of department personnel. Furthermore, the form was completed by parents for patients over 18 year-old or by the help of first-rank relative for those having psychiatric disorders or anybody who wasn't able to complete the form. In order to identify the causes of self-discharge, 18 variables were determined which were categorized in three general items and five main groups. Data were entered into the SPSS15 and were analyzed using descriptive statistics indices. RESULTS: According to the results, 94441 were discharged from the university hospitals which 7967 patients (8.4 %) of them were self-discharged during the 6 month study period. Regarding admission type, 269 (3.3 %), (54.5 %) were admitted into the hospital by pre-determined appointment and as usual patients, respectively, and the rest were admitted by emergency department. Also, 31.4%(2504) were hospitalized in surgery ward, 63% (5026) in medical ward, 4.6% (374) in intensive care unit (ICU) and the rest were hospitalized in the psychiatric ward. The most important reasons for self-discharge were related to: 1-factors affecting patient illness (54.3%), 2-environmental issues as well as patients' accompanying (37.6%) and 3-managerial and medical reasons(7.9%), respectively. CONCLUSION: Our study showed the same results for Discharge against medical advice rate as the others. From the view point of treatment management, its causes should be considered and practices should be done to improve the conditions. Meanwhile, the current self-discharge form doesn't reflect the causes of the problem and it should be revised. PMID- 25126019 TI - Effects of lipoic Acid on acrylamide induced testicular damage. AB - INTRODUCTION: Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress. AIM OF THE STUDY: This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues. MATERIAL AND METHODS: Forty adult male rats were divided into four groups (10 rats each). Control group; acrylamide treated group administered acrylamide 0.05% (w/v) in drinking water for 21 days; alpha-lipoic acid group received basal diet supplemented with 1% alpha-lipoic acid and forth group was exposed to acrylamide and treated with alpha-lipoic acid at the same doses and treatment regimen mentioned before. RESULTS: The administration of acrylamide resulted in significant elevation in testicular and epididymal malondialdehyde level (MDA) and significant reduction in the level of reduced glutathione (GSH) and the activities of glutathione-S transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GR). Also, acrylamide significantly reduced serum total testosterone and progesterone but increased estradiol (E2) levels. Treatment with alpha-lipoic acid prior to acrylamide induced protective effects and attenuated these biochemical changes. CONCLUSION: Alpha-lipoic acid has been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by acrylamide administration. PMID- 25126020 TI - Correlates of hypertension among adult men and women in kosovo. AB - AIM: We aimed to assess the independent socioeconomic, behavioral and psychosocial correlates of hypertension among the adult population of Kosovo. METHODS: This was a cross-sectional study carried out in Pristina in 2012-2013 which included a large representative sample of 1793 consecutive primary health care users aged >=35 years (mean age: 51.2+/-6.7 years; 52.5% women; overall response: 95%). Systolic and diastolic blood pressure was measured, whereas demographic and socioeconomic characteristics (age, sex, marital status, place of residence, education, employment status and income), lifestyle factors (smoking, alcohol intake, physical exercise and dietary fat intake) and psychosocial factors (hostility and reaction to transition) were assessed through a structured questionnaire. Multivariable-adjusted binary logistic regression was used to assess the independent "predictors" of hypertension. RESULTS: Upon simultaneous adjustment in a backward stepwise elimination procedure for all socioeconomic characteristics, lifestyle factors and psychosocial factors, significant positive correlates of hypertension were older age (OR=1.03, 95%CI=1.01-1.05), male gender (OR=1.41, 95%CI=1.19-1.58), a lower educational attainment (OR=1.36, 95%CI=1.08 1.67), smoking (OR=1.53, 95%CI=1.28-2.16), physical inactivity (OR=1.98, 95%CI=1.46-2.74) and hostility (OR=1.42, 95%CI=1.17-2.08). CONCLUSIONS: Findings from this study conducted in transitional Kosovo are generally in line with previous reports from the Western Balkan countries and beyond. Decision-makers and policymakers should be aware of the rising trend and socioeconomic, behavioral and psychosocial determinants of hypertension in post-war Kosovo. PMID- 25126021 TI - Bidirectional Associations Among Sensitive Parenting, Language Development, and Social Competence. AB - Rapid changes in language skills and social competence, both of which are linked to sensitive parenting, characterize early childhood. The present study examines bidirectional associations among mothers' sensitive parenting and children's language skills and social competence from 24 to 36 months in a community sample of 174 families. In addition, this study examines how these developmental pathways vary by child sex. Findings indicate stability across time in sensitive parenting, expressive language skills, and social competence, as well as positive main effects of sensitive parenting on expressive and receptive language skills for girls and boys. We find mixed evidence over time of reciprocal links between social competence and sensitive parenting. Further, boys' receptive language skills at 24 months uniquely contribute to increases in mothers' observed sensitive parenting from 24 to 36 months. These findings highlight the utility of applying transactional frameworks to the study of sex-based differences in early developmental processes. PMID- 25126022 TI - What are we 'tweeting' about obesity? Mapping tweets with Topic Modeling and Geographic Information System. AB - Public health related tweets are difficult to identify in large conversational datasets like Twitter.com. Even more challenging is the visualization and analyses of the spatial patterns encoded in tweets. This study has the following objectives: How can topic modeling be used to identify relevant public health topics such as obesity on Twitter.com? What are the common obesity related themes? What is the spatial pattern of the themes? What are the research challenges of using large conversational datasets from social networking sites? Obesity is chosen as a test theme to demonstrate the effectiveness of topic modeling using Latent Dirichlet Allocation (LDA) and spatial analysis using Geographic Information System (GIS). The dataset is constructed from tweets (originating from the United States) extracted from Twitter.com on obesity related queries. Examples of such queries are 'food deserts', 'fast food', and 'childhood obesity'. The tweets are also georeferenced and time stamped. Three cohesive and meaningful themes such as 'childhood obesity and schools', 'obesity prevention', and 'obesity and food habits' are extracted from the LDA model. The GIS analysis of the extracted themes show distinct spatial pattern between rural and urban areas, northern and southern states, and between coasts and inland states. Further, relating the themes with ancillary datasets such as US census and locations of fast food restaurants based upon the location of the tweets in a GIS environment opened new avenues for spatial analyses and mapping. Therefore the techniques used in this study provide a possible toolset for computational social scientists in general and health researchers in specific to better understand health problems from large conversational datasets. PMID- 25126023 TI - Surface Mediated Structures: Stabilization of Metastable Polymorphs on the Example of Paracetamol. AB - The preparation of typically thermodynamically unstable polymorphic structures is a challenge. However, solid surfaces are well established aids for the formation and stabilization of polymorphic structures within, for instance, organic electronics. In this study, we report the stabilization of a pharmaceutically relevant substance via a solid surface at ambient conditions. Form III of paracetamol, which is typically unstable in the bulk at standard conditions, can be stabilized with a model silica surface by a standard spin coating procedure followed by rapid heat treatment. Such a preparation technique allows the use of atomic force microscopy and grazing incidence X-ray diffraction measurements revealing detailed information on the morphology and structure of the polymorph. Furthermore, the results exhibit that this polymorph is stable over a long period of time revealing surface mediated stabilization. These findings demonstrate a novel approach to provide thermodynamic stability when applied to similar molecules with specific applications. PMID- 25126025 TI - Joy in the practice of sleep medicine. PMID- 25126026 TI - The case of simultaneous submission: "Flying too close to the sun". PMID- 25126024 TI - Prevalence and correlates of HIV risk among adolescents and young adults reporting drug use: Data from an urban Emergency Department in the U.S. AB - Adolescents and young adults who use substances are at particularly high risk for contracting Human Immunodeficiency Virus (HIV). The Emergency Department (ED) is a critical location for HIV prevention for at-risk youth. To inform future interventions in the ED, this study identifies correlates of HIV risk behaviors among substance using youth seeking ED care. Among 600 14-24-year-olds with past 6-month drug use, bivariate correlates of HIV risk included: older age, female gender, depressive symptoms, alcohol use, marijuana use, other drug use, and dating, peer, and community violence. Regression analyses indicated that older age, marijuana use, and dating violence were positively related to HIV risk. Results suggest HIV prevention efforts for youth in the urban ED should address marijuana use and dating violence as well as sexual risk behaviors. PMID- 25126028 TI - Resistant hypertension and untreated severe sleep apnea: slowly gaining insight. PMID- 25126027 TI - Association of severe obstructive sleep apnea and elevated blood pressure despite antihypertensive medication use. AB - RATIONALE: We hypothesized that untreated severe obstructive sleep apnea (OSA) is associated with elevated ambulatory blood pressure (BP) in subjects with high cardiovascular disease (CVD) risk despite medical management. METHODS: Data from the baseline examination of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a 4-site randomized controlled trial were analyzed. Individuals with moderate-severe OSA (apnea hypopnea index, AHI = 15-50) and cardiovascular risk were recruited from cardiology practices. Those with hypertension were included. Intensive antihypertensive regimen (IAR) was defined as >= 3 antihypertensives including a diuretic. Definitions were: controlled BP (BP < 130/80), uncontrolled elevated BP (BP >= 130/80 not on IAR) and resistant elevated BP (BP >= 130/80 mm Hg despite IAR). Associations of untreated severe OSA (AHI >= 30) and uncontrolled and resistant elevated BP were evaluated using logistic regression analyses adjusted for age, sex, race, body mass index, smoking status, diabetes, and CVD. RESULTS: Among the 284 participants (mean age 63.1 +/- 7.2 years, 23.6% with severe OSA), 61.6% had controlled BP, 28.5% had uncontrolled elevated BP, and 9.9% had resistant elevated BP. Among participants prescribed IAR, resistant elevated BP was more prevalent in those with severe compared to moderate OSA (58.3% vs. 28.6%, p = 0.01). Participants with severe OSA had a 4-fold higher adjusted odds of resistant elevated BP (OR 4.1, 95% CI: 1.7-10.2), a finding not reproduced in the absence of IAR use. CONCLUSIONS: Among patients with increased cardiovascular risk and moderate to severe OSA, untreated severe compared to moderate OSA was associated with elevated BP despite IAR suggesting untreated severe OSA contributes to poor BP control despite aggressive medication use. COMMENTARY: A commentary on this article appears in this issue on page 845. PMID- 25126030 TI - Effect of opioids on sleep and breathing in chronic pain patients. PMID- 25126029 TI - Sleep disordered breathing and chronic respiratory failure in patients with chronic pain on long term opioid therapy. AB - STUDY OBJECTIVES: The use of opioid medication for chronic pain has been increasing. The main aim of this study was to assess how many patients on opioids for chronic pain had sleep disordered breathing (SDB) and the type of SDB. The impact of these medications on daytime arterial blood gas (ABG) measurements and psychomotor vigilance was also studied. METHODS: Twenty-four patients (aged 18-75 years) on long-term opioids were prospectively recruited. Patients underwent home polysomnogram (PSG), psychomotor vigilance testing (PVT), and awake daytime ABG. Overnight PSG findings were compared to those of patients matched for age, sex, and BMI referred to our sleep service for evaluation of SDB. PVT results in the patient cohort were compared to PVT in healthy controls. RESULTS: Forty-six percent of opioid patients had severe SDB as defined by an apnea hypopnea index (AHI) > 30/h. The severity of SDB was similar in opioid-treated pain clinic patients and sleep clinic patients (mean +/- SD AHI: Opioid-treated patients 32.7 +/- 25.6; Sleep Study comparator group 28.9 +/- 24.6, p = 0.6). Opioid patients had a higher frequency of central apneas and a lower arousal index (CAI: 3.9 +/- 8.3 vs. 0.3 +/- 0.5 events/h; p = 0.004, AI 8.0 +/- 4.1 vs. 20.1 +/- 13.8, p < 0.001). Pain clinic patients had impaired gas exchange during sleep and wakefulness. Nine of 20 (45%) had daytime hypercapnia, indicating a surprising number were in chronic respiratory failure. Morphine equivalent doses correlated with the severity of SDB. PVT was impaired when compared to a healthy PVT comparator group (RT: Opioid-treated patients 0.43 +/- 0.27: Healthy PVT comparator group 0.28 +/- 0.03 sec; p < 0.001). CONCLUSIONS: Patients on long term opioids frequently have severe SDB, which in part is central in origin. PVT was markedly impaired. Half of the patients studied have evidence of chronic ventilatory failure. COMMENTARY: A commentary on this article appears in this issue on page 853 PMID- 25126031 TI - A novel adaptive servoventilation (ASVAuto) for the treatment of central sleep apnea associated with chronic use of opioids. AB - STUDY OBJECTIVES: To compare the efficacy and patient comfort of a new mode of minute ventilation-targeted adaptive servoventilation (ASVAuto) with auto titrating expiratory positive airway pressure (EPAP) versus bilevel with back-up respiratory rate (bilevel-ST) in patients with central sleep apnea (CSA) associated with chronic use of opioid medications. METHODS: Prospective, randomized, crossover polysomnography (PSG) study. Eighteen consecutive patients (age >= 18 years) who had been receiving opioid therapy (>= 6 months), and had sleep disordered breathing with CSA (central apnea index [CAI] >= 5) diagnosed during an overnight sleep study or positive airway pressure (PAP) titration were enrolled to undergo 2 PSG studies-one with ASVAuto and one with bilevel-ST. Patients completed 2 questionnaires after each PSG; Morning After Patient Satisfaction Questionnaire and PAP Comfort Questionnaire. RESULTS: Patients had a mean age of 52.9 +/- 15.3 years. PSG prior to randomization showed an apnea hypopnea index (AHI) of 50.3 +/- 22.2 and CAI of 13.0 +/- 18.7. Titration with ASVAuto versus bilevel-ST showed that there were significant differences with respect to AHI and CAI. The AHI and CAI were significantly lower on ASVAuto than bilevel-ST (2.5 +/- 3.5 versus 16.3 +/- 20.9 [p = 0.0005], and 0.4 +/- 0.8 versus 9.4 +/- 18.8 [p = 0.0002], respectively). Respiratory parameters were normalized in 83.3% of patients on ASVAuto versus 33.3% on bilevel-ST. Patients felt more awake and alert on ASVAuto than bilevel-ST based on scores from Morning After Patient Satisfaction Questionnaire (p = 0.0337). CONCLUSIONS: The ASVAuto was significantly more effective than bilevel-ST for the treatment of CSA associated with chronic opioid use. PMID- 25126032 TI - Assessment of a neck-based treatment and monitoring device for positional obstructive sleep apnea. AB - STUDY OBJECTIVES: A majority of patients diagnosed with obstructive sleep apnea are position dependent whereby they are at least twice as severe when sleeping supine (POSA). This study evaluated the accuracy and efficacy of a neck-worn device designed to limit supine sleep. The study included nightly measurements of snoring, sleep/wake, time supine, and the frequency and duration of feedback to monitor compliance. METHODS: Thirty patients between ages 18 and 75 years, BMI <= 35 with an overall apnea-hypopnea index (AHI) >= 5 and an overall AHI >= 1.5 times the non-supine AHI, and an Epworth score >= 5 were prospectively studied. Subjective reports and polysomnography were used to assess efficacy resulting from 4 weeks of in-home supine-avoidance therapy and to measure device accuracy. From 363 polysomnography reports, 209 provided sufficient positional data to estimate one site's prevalence of positional OSA. RESULTS: In 83% of participants exhibiting > 50% reduction in overall AHI, the mean and median reductions were 69% and 79%. Significant reductions in the overall and supine AHI, apnea index, percent time SpO2 < 90%, and snoring contributed to significant improvements in stage N1 and N2 sleep, reductions in cortical arousals and awakenings, and improved depression scores. Supine position was under-detected by > 5% in 3% of cases. Sleep efficiency by neck actigraphy was within 10% of polysomnography in 87% of the studies when position feedback was delivered. The prevalence of POSA was consistently > 70% when the overall AHI was < 60. CONCLUSIONS: The neck position therapy device is accurate and effective in restricting supine sleep, improving AHI, sleep architecture and continuity, and monitoring treatment outcomes. PMID- 25126033 TI - Complete blood count alterations after six months of continuous positive airway pressure treatment in patients with severe obstructive sleep apnea. AB - STUDY OBJECTIVES: The cardiovascular complications caused by obstructive sleep apnea (OSA) decrease after continuous positive airway pressure treatment (CPAP). Mean platelet volume (MPV), platelet distribution width (PDW), and red cell distribution width (RDW) are newly recognized tools for assessing cardiovascular risk. METHODS: From a selection of patients with symptoms of nocturnal snoring and/or excessive daytime sleepiness, 36 males with an apnea-hypopnea index (AHI) > 30/h and 22 age-matched normal male controls with AHI < 5/h were included. Patients with OSA underwent another night of CPAP titration, and 11 patients were excluded at the 6-month evaluation due to poor compliance with the home CPAP therapy. Complete blood count parameters of compliant patients and the control group were evaluated. RESULTS: Compared to controls, MPV values were significantly higher (p = 0.025) in OSA patients, but no significant differences in PDW or RDW were found (p > 0.05). Six months of CPAP therapy resulted in significantly lower MPV values but increased values of PDW and RDW in patients with severe OSA (p = 0.001, p = 0.007, p = 0.001, respectively). CONCLUSION: Our data suggest that complete blood count parameters in OSA patients such as MPV, PDW and RDW change significantly after CPAP therapy. PMID- 25126034 TI - Home-based diagnosis of obstructive sleep apnea in an urban population. AB - STUDY OBJECTIVES: Home-based diagnosis of obstructive sleep apnea (OSA) with portable monitoring (PM) is increasingly utilized, but remains understudied in underserved and minority populations. We tested the feasibility of home PM in an urban population at risk for OSA compared to in-laboratory polysomnography (PSG) and examined patient preference with respect to home PM versus PSG. METHODS: Randomized crossover study of home PM (WatchPAT200) and in-laboratory simultaneous PSG and PM in 75 urban African Americans with high pre-test probability of OSA, identified with the Berlin questionnaire. RESULTS: Fifty seven of 75 participants were women, average age 45 +/- 11 years (mean +/- SD), 35% with <= high school education, and 76% with annual household income < $50,000. Technical failure rates were 5.3% for home vs. 3.1% for in-laboratory PM. There was good agreement between apnea hypopnea index on PSG; AHIPSG and AHI on home PM (mean +/- 2 SD of the differences = 0.64 +/- 46.5 and intraclass correlation coefficient; ICC = 0.73). The areas under the curve for the receiver operator characteristic curves for home PM were 0.90 for AHIPSG >= 5, 0.95 for AHIPSG >= 10, and 0.92 for AHIPSG >= 15. 62/75 (82%) participants preferred home over in-laboratory testing. CONCLUSIONS: Home PM for diagnosis of OSA in a high risk urban population is feasible, accurate, and preferred by patients. As home PM may improve access to care, the cost-effectiveness of this diagnostic strategy for OSA should be examined in underserved urban and rural populations. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, identifier: NCT01997723. PMID- 25126035 TI - The efficacy of a chinstrap in treating sleep disordered breathing and snoring. AB - STUDY OBJECTIVES: A previously published case report suggested that a chinstrap alone might improve obstructive sleep apnea (OSA). We conducted this study to determine whether a chinstrap was a feasible alternative to continuous positive airway pressure (CPAP) in patients with OSA. METHODS: 26 adult patients with OSA (apnea-hypopnea index [AHI] > 5/h on diagnostic polysomnogram [PSG]) underwent a modified split-night PSG, using only a chinstrap for the first 2 hours of sleep, followed by CPAP titration for the remainder of the night. Improvements in AHI, arterial oxygen saturation (SpO2), and snoring with chinstrap use were compared to results with optimal CPAP pressures. RESULTS: There was no significant difference between the diagnostic PSG and the chinstrap portion of the split night PSG in the following parameters: general AHI (median [IQR] 16.0/h [9.7 26.0] vs. 25.9/h [10.7-42.7]), SpO2 nadir (84.0% [80.5-87.5] vs. 87.0 [84.0 88.5]), AHI in REM sleep (26.7/h [16.8-43.7] vs. 42.4/h [21.3-57.7]), AHI in supine sleep (24.9/h [11.9-51.5] vs. 29.8/h [11.7-55.5]), snoring index (253.2/h [147.5-353.1] vs. 180.0/h [9.8-393.3]) or subjective snoring scale (3.0 [0.8-3.0] vs. 2.5 [0.4-3.0]). The AHI and SpO2 nadir in the 13 patients with mild OSA also did not improve with chinstrap use (9.6/h [8.1-12.2] vs. 10.6/h [6.8-35.4] and 87.0% [83.0-90.0] vs. 88.0% [87.0-89.0]). All these parameters showed significant improvement with optimal CPAP titration (p < 0.05). CONCLUSIONS: A chinstrap alone is not an effective treatment for OSA. It does not improve sleep disordered breathing, even in mild OSA, nor does it improve the AHI in REM sleep or supine sleep. It is also ineffective in improving snoring. PMID- 25126036 TI - Effect of sensory stimuli on restless legs syndrome: a randomized crossover study. AB - STUDY OBJECTIVE: A variety of sensory stimuli relieve restless legs syndrome symptoms. Because systematic evaluations of sensory stimulation in restless legs syndrome are largely lacking, we performed a randomized crossover study to evaluate the effect of external sensory stimulation on restless legs syndrome symptoms. METHODS: Eighteen patients underwent 3 consecutive suggestive immobilization tests with the order of the following 3 conditions randomly assigned: no electrical stimulation (condition 1), tactile and proprioceptive sensory stimulation (condition 2), and tactile sensory stimulation only (condition 3). Restless legs syndrome symptoms were quantified by visual analog scales, and periodic leg movements during wake were measured. RESULTS: Baseline visual analogue scale score was 4.5 (range 0-60) in condition 1, 10.5 (range 0 96) in condition 2, and 8.5 in condition 3 (p = 0.21). There was a tendency towards a higher maximum visual analogue scale score and visual analogue scale score at the end of the suggested immobilization test in the conditions with tactile sensory stimulation, though not significant (p = 0.74 and p = 0.29, respectively). Fifteen patients suffered from periodic leg movements during wake. Median indices were 18 (range 0-145) in condition 1, 26 (range 0-190) in condition 2, and 49 (range 0-228) in condition 3 (p = 0.76). CONCLUSIONS: We found a tendency towards less leg discomfort in the conditions in which an external sensory input was applied. This potential benefit of sensory stimuli on restless legs syndrome severity merits further investigation as this could open new ways towards a better pathophysiological understanding and non pharmacological treatments. PMID- 25126037 TI - Drug testing in children with excessive daytime sleepiness during multiple sleep latency testing. AB - STUDY OBJECTIVE: To determine the incidence of positive drug screens in children undergoing a multiple sleep latency test (MSLT) for evaluation of excessive daytime sleepiness (EDS). METHODS: A retrospective analysis was performed in children evaluated at the Boston Children's Hospital Sleep Center between 1998 and 2013 who underwent MSLT for EDS with a concurrent urine and/or serum drug screen. RESULTS: A total of 210 MSLTs were accompanied by drug testing. Children were 12.7 +/- 3.7 years old (mean +/- SD), 43% were female, and 24% had narcolepsy. Positive tests were obtained in 32% for caffeine, 5% for prescription medications, and 4% for over-the-counter drugs. No drugs of abuse were identified. Children testing positive for caffeine were older (13.8 +/- 3.5 vs. 12.4 +/- 3.7) and more likely female (59% vs. 36%), but did not differ in MSLT or overnight polysomnographic parameters compared to children without caffeine detected. Overall, only 14% had specific documentation regarding caffeine intake, though 90% were referred from a sleep clinic. Of the children testing positive for caffeine, 5% acknowledged use, 3% denied use, and 92% did not have a documented caffeine intake history during their sleep clinic visit. CONCLUSIONS: Routine drug testing for drugs of abuse during an MSLT for EDS yielded no positive results over a 15-year period, indicating that this routine practice is unnecessary in our pediatric population without specific concerns. However, objective evidence for caffeine exposure was found in 32% of tested children undergoing an MSLT. Sleep physicians rarely documented the caffeine intake history during clinic visits for EDS. PMID- 25126038 TI - Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children? AB - STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. METHODS: Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 +/- 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. RESULTS: Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] >= 1.5, mean 8.3 +/- 10.6) and 24 without OSA (AHI 0.9 +/- 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). CONCLUSION: Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT00233194. PMID- 25126039 TI - Feasibility of comprehensive, unattended ambulatory polysomnography in school aged children. AB - STUDY OBJECTIVES: Although unattended ambulatory polysomnography (PSG) is frequently performed in adults, few studies have been performed in children. The objective of this study was to evaluate the feasibility of comprehensive, ambulatory PSG, including electroencephalography, in school-aged children in the home environment. METHODS: A total of 201 children, born premature with birth weights of 500-1,250 grams, currently aged 5-12 years and living in Canada and Australia, underwent unattended ambulatory PSG. RESULTS: PSG was initially technically satisfactory in 183 (91%) cases. Fourteen studies were satisfactory when repeated, resulting in an overall satisfactory rate of 197 (98%). Artifact free signals were obtained for >= 75% of recording time in more than 92% of subjects, with the exception of nasal pressure, which was satisfactory for >= 75% of recording time in only 67% of subjects. However, thermistry signals were satisfactory for >= 75% of recording time in 92% of subjects, and some measure of airflow was present for >= 75% of recording time in 96% of subjects. Children slept very well, with a long total sleep time (534 +/- 73 [mean +/- SD] minutes), high sleep efficiency (92% +/- 5%), and low arousal index (9 +/- 3/h). Parents and children reported a high rate of satisfaction with the study. CONCLUSIONS: This large, international study has shown that comprehensive, unattended, ambulatory PSG is feasible, technically adequate and well-tolerated in school aged children when performed under research conditions. Further studies regarding the cost efficacy of this approach, and generalizability of the findings to a clinical population, are warranted. PMID- 25126041 TI - Adult NREM parasomnia associated with lancinating throat pain. AB - We report the case of a 30-year-old woman presenting with dangerous nocturnal NREM episodes with the clinical feature of lancinating throat pain. We hypothesize that the pain may have represented sensory hallucination analogous to commonly recognized visual images associated with NREM parasomnias. This case is also unusual for probable psychological triggers that could play a role in the pathogenesis of the disease, as evidenced by successful psychotherapy. PMID- 25126040 TI - Assessing and predicting the likelihood of interventions during routine annual follow-up visits for management of obstructive sleep. AB - STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) on established positive airway pressure (PAP) treatment are often advised routine annual follow up visits to assess ongoing effectiveness and address problems associated with therapy. This study evaluates the clinical utility of annual face-to-face follow up visits. DESIGN: We performed a retrospective chart review of OSA patients on PAP who had completed a routine annual follow-up visit. Demographics, polysomnography, PAP compliance, Epworth Sleepiness Scale (ESS), subjective complaints (efficacy and interface issues, equipment malfunction, prescription renewal), objective findings (efficacy or leak issues, equipment problems), and visit-specific interventions were recorded. We determined relationships between patient provided information and likelihood of therapeutic versus administrative interventions. SETTING: Academic sleep center. MEASUREMENTS AND RESULTS: Among 716 patients who met study criteria, we abstracted data on 180 randomly selected patients. On multivariate analyses, only subjective complaints or objective findings by providers were associated with a therapeutic intervention (p < 0.0001). Though most patients (55 of 63 patients, 87.3%) who required therapeutic interventions had objective findings, without subjective complaints, the odds of such findings were only 0.12 (95% CI = 0.06-0.24, p < 0.0001). Without subjective complaints, the likelihood of a therapeutic intervention was 0.07 (95% CI = 0.03 0.15, p < 0.001). CONCLUSION: Our data suggests that in the absence of a subjective complaint, an annual follow-up is more likely to require administrative rather than face-to-face clinical intervention. Designing a clinic model to account for this might reduce resource utilization. However, the value and optimal timing of "routine" annual follow-up visits requires further evaluation. PMID- 25126043 TI - Cognitive benefits of computer games for older adults. AB - The purpose of this paper is to develop a basis for the hypothesis that digital action games may produce cognitive benefits for older adults. First, a discussion of the relationship between cognitive and physical health shows the increasing weight given to the role of declines in cognition in the development of dependency in older adult population studies. Second, evidence that cognitive training produces 'far transfer' in elders is presented. The key issue is that one approach, known as extended practice training, has been successful in producing far transfer to memory and other processes. Its principles, which are consistent with those associated with positive brain plasticity effects, are identified. Those principles are then related to the mechanics of digital action games, which also have the important added feature of producing the experiences of presence, engagement, and flow, the subjective elements of game play that are likely to sustain interest and emotional investment in the skills practiced so that the play produces cognitive benefits. The specific cognitive abilities proposed to be improved by different types of game genres are outlined, and recent developments in game and interface design that may affect the willingness of older adults to play are described. PMID- 25126042 TI - Sleep-related violence and sexual behavior in sleep: a systematic review of medical-legal case reports. AB - OBJECTIVE: To review systematically medical-legal cases of sleep-related violence (SRV) and sexual behavior in sleep (SBS). SEARCH METHODS: We searched Pubmed and PsychINFO (from 1980 to 2012) with pre-specified terms. We also searched reference lists of relevant articles. SELECTION CRITERIA: Case reports in which a sleep disorder was purported as the defense during a criminal trial and in which information about the forensic evaluation of the defendant was provided. DATA EXTRACTION AND ANALYSIS: Information about legal issues, defendant and victim characteristics, circumstantial factors, and forensic evaluation was extracted from each case. A qualitative-comparative assessment of cases was performed. RESULTS: Eighteen cases (9 SRV and 9 SBS) were included. The charge was murder or attempted murder in all SRV cases, while in SBS cases the charge ranged from sexual touching to rape. The defense was based on sleepwalking in 11 of 18 cases. The trial outcome was in favor of the defendant in 14 of 18 cases. Defendants were relatively young males in all cases. Victims were usually adult relatives of the defendants in SRV cases and unrelated young girls or adolescents in SBS cases. In most cases the criminal events occurred 1-2 hours after the defendant's sleep onset, and both proximity and other potential triggering factors were reported. The forensic evaluations widely differed from case to case. CONCLUSION: SRV and SBS medical-legal cases did not show apparent differences, except for the severity of the charges and the victim characteristics. An international multidisciplinary consensus for the forensic evaluation of SRV and SBS should be developed as an urgent priority. PMID- 25126044 TI - The regulation of coenzyme q biosynthesis in eukaryotic cells: all that yeast can tell us. AB - Coenzyme Q (CoQ) is a mitochondrial lipid, which functions mainly as an electron carrier from complex I or II to complex III at the mitochondrial inner membrane, and also as antioxidant in cell membranes. CoQ is needed as electron acceptor in beta-oxidation of fatty acids and pyridine nucleotide biosynthesis, and it is responsible for opening the mitochondrial permeability transition pore. The yeast model has been very useful to analyze the synthesis of CoQ, and therefore, most of the knowledge about its regulation was obtained from the Saccharomyces cerevisiae model. CoQ biosynthesis is regulated to support 2 processes: the bioenergetic metabolism and the antioxidant defense. Alterations of the carbon source in yeast, or in nutrient availability in yeasts or mammalian cells, upregulate genes encoding proteins involved in CoQ synthesis. Oxidative stress, generated by chemical or physical agents or by serum deprivation, modifies specifically the expression of some COQ genes by means of stress transcription factors such as Msn2/4p, Yap1p or Hsf1p. In general, the induction of COQ gene expression produced by metabolic changes or stress is modulated downstream by other regulatory mechanisms such as the protein import to mitochondria, the assembly of a multi-enzymatic complex composed by Coq proteins and also the existence of a phosphorylation cycle that regulates the last steps of CoQ biosynthesis. The CoQ biosynthetic complex assembly starts with the production of a nucleating lipid such as HHB by the action of the Coq2 protein. Then, the Coq4 protein recognizes the precursor HHB acting as the nucleus of the complex. The activity of Coq8p, probably as kinase, allows the formation of an initial pre complex containing all Coq proteins with the exception of Coq7p. This pre-complex leads to the synthesis of 5-demethoxy-Q6 (DMQ6), the Coq7p substrate. When de novo CoQ biosynthesis is required, Coq7p becomes dephosphorylated by the action of Ptc7p increasing the synthesis rate of CoQ6. This critical model is needed for a better understanding of CoQ biosynthesis. Taking into account that patients with CoQ10 deficiency maintain to some extent the machinery to synthesize CoQ, new promising strategies for the treatment of CoQ10 deficiency will require a better understanding of the regulation of CoQ biosynthesis in the future. PMID- 25126046 TI - Clinical presentations of coenzyme q10 deficiency syndrome. AB - Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous syndrome which has been associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) nephropathy, (4) cerebellar ataxia, and (5) isolated myopathy. Of these phenotypes, cerebellar ataxia and syndromic or isolated nephrotic syndrome are the most common. CoQ10 deficiency predominantly presents in childhood. To date, causative mutations have been identified in a small proportion of patients, making it difficult to identify a phenotype-genotype correlation. Identification of CoQ10 deficiency is important because the disease, in particular muscle symptoms and nephropathy, frequently responds to CoQ10 supplementation. PMID- 25126047 TI - Biochemical diagnosis of coenzyme q10 deficiency. AB - Coenzyme Q10 (CoQ10) deficiency appears to have a particularly heterogeneous clinical presentation. However, there appear to be 5 recognisable clinical phenotypes: encephalomyopathy, severe infantile multisystemic disease, nephropathy, cerebellar ataxia, and isolated myopathy. However, although useful, clinical symptoms alone are insufficient for the definitive diagnosis of CoQ10 deficiency which relies upon biochemical assessment of tissue CoQ10 status. In this article, we review the biochemical methods used in the diagnosis of human CoQ10 deficiency and indicate the most appropriate tissues for this evaluation. PMID- 25126045 TI - Coenzyme q and the respiratory chain: coenzyme q pool and mitochondrial supercomplexes. AB - Two alternative models of organization of the mitochondrial electron transport chain (mETC) have been alternatively favored or questioned by the accumulation evidences of different sources, the solid model or the random collision model. Both agree in the number of respiratory complexes (I-IV) that participate in the mETC, but while the random collision model proposes that Complexes I-IV do not interact physically and that electrons are transferred between them by coenzyme Q and cytochrome c, the solid model proposes that all complexes super-assemble in the so-called respirasome. Recently, the plasticity model has been developed to incorporate the solid and the random collision model as extreme situations of a dynamic organization, allowing super-assembly free movement of the respiratory complexes. In this review, we evaluate the supporting evidences of each model and the implications of the super-assembly in the physiological role of coenzyme Q. PMID- 25126048 TI - Genetics of coenzyme q10 deficiency. AB - Coenzyme Q10 (CoQ10) is an essential component of eukaryotic cells and is involved in crucial biochemical reactions such as the production of ATP in the mitochondrial respiratory chain, the biosynthesis of pyrimidines, and the modulation of apoptosis. CoQ10 requires at least 13 genes for its biosynthesis. Mutations in these genes cause primary CoQ10 deficiency, a clinically and genetically heterogeneous disorder. To date mutations in 8 genes (PDSS1, PDSS2, COQ2, COQ4, COQ6, ADCK3, ADCK4, and COQ9) have been associated with CoQ10 deficiency presenting with a wide variety of clinical manifestations. Onset can be at virtually any age, although pediatric forms are more common. Symptoms include those typical of respiratory chain disorders (encephalomyopathy, ataxia, lactic acidosis, deafness, retinitis pigmentosa, hypertrophic cardiomyopathy), but some (such as steroid-resistant nephrotic syndrome) are peculiar to this condition. The molecular bases of the clinical diversity of this condition are still unknown. It is of critical importance that physicians promptly recognize these disorders because most patients respond to oral administration of CoQ10. PMID- 25126049 TI - Pathomechanisms in coenzyme q10-deficient human fibroblasts. AB - Primary coenzyme Q10 (CoQ10) deficiency is a rare mitochondrial disorder associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) cerebellar ataxia, (4) isolated myopathy, and (5) steroid-resistant nephrotic syndrome. Growth retardation, deafness and hearing loss have also been described in CoQ10-deficient patients. This heterogeneity in the clinical presentations suggests that multiple pathomechanisms may exist. To investigate the biochemical and molecular consequences of CoQ10 deficiency, different laboratories have studied cultures of skin fibroblasts from patients with CoQ10 deficiency. In this review, we summarize the results obtained in these studies over the last decade. PMID- 25126050 TI - Invertebrate models for coenzyme q10 deficiency. AB - The human syndrome of coenzyme Q (CoQ) deficiency is a heterogeneous mitochondrial disease characterized by a diminution of CoQ content in cells and tissues that affects all the electron transport processes CoQ is responsible for, like the electron transference in mitochondria for respiration and ATP production and the antioxidant capacity that it exerts in membranes and lipoproteins. Supplementation with external CoQ is the main attempt to address these pathologies, but quite variable results have been obtained ranging from little response to a dramatic recovery. Here, we present the importance of modeling human CoQ deficiencies in animal models to understand the genetics and the pathology of this disease, although the election of an organism is crucial and can sometimes be controversial. Bacteria and yeast harboring mutations that lead to CoQ deficiency are unable to grow if they have to respire but develop without any problems on media with fermentable carbon sources. The complete lack of CoQ in mammals causes embryonic lethality, whereas other mutations produce tissue specific diseases as in humans. However, working with transgenic mammals is time and cost intensive, with no assurance of obtaining results. Caenorhabditis elegans and Drosophila melanogaster have been used for years as organisms to study embryonic development, biogenesis, degenerative pathologies, and aging because of the genetic facilities and the speed of working with these animal models. In this review, we summarize several attempts to model reliable human CoQ deficiencies in invertebrates, focusing on mutant phenotypes pretty similar to those observed in human patients. PMID- 25126051 TI - An overview of current mouse models recapitulating coenzyme q10 deficiency syndrome. AB - Coenzyme Q (CoQ), also known as ubiquinone, is an essential lipophilic molecule present in all cellular membranes and involved in a variety of cellular functions, in particular as an electron carrier in the mitochondrial respiratory chain and as a potent antioxidant. CoQ is synthesized endogenously through a complex metabolic pathway involving over 10 different components. Primary CoQ10 deficiency in humans, due to mutations in genes involved in CoQ biosynthesis, is a heterogeneous group of rare disorders presenting severe and complex clinical symptoms. The generation of mouse models deficient in CoQ is important to further clarify the cellular function of CoQ and to unravel the complexity in the pathophysiological consequences of CoQ deficiency. This review summarizes the current knowledge on mouse models of primary CoQ deficiency. PMID- 25126053 TI - Learning with repeated-game strategies. AB - We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2 * 2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we find that the strategy with the most occurrences is the "Grim-Trigger." In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the "Win-Stay, Lose-Shift" and "Grim-Trigger" strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non cooperative outcomes. PMID- 25126052 TI - Coenzyme q10 therapy. AB - For a number of years, coenzyme Q10 (CoQ10) was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in blood plasma, and extensively investigated its antioxidant role. These 2 functions constitute the basis for supporting the clinical use of CoQ10. Also, at the inner mitochondrial membrane level, CoQ10 is recognized as an obligatory cofactor for the function of uncoupling proteins and a modulator of the mitochondrial transition pore. Furthermore, recent data indicate that CoQ10 affects the expression of genes involved in human cell signaling, metabolism and transport, and some of the effects of CoQ10 supplementation may be due to this property. CoQ10 deficiencies are due to autosomal recessive mutations, mitochondrial diseases, aging-related oxidative stress and carcinogenesis processes, and also statin treatment. Many neurodegenerative disorders, diabetes, cancer, and muscular and cardiovascular diseases have been associated with low CoQ10 levels as well as different ataxias and encephalomyopathies. CoQ10 treatment does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Oral administration of CoQ10 is a frequent antioxidant strategy in many diseases that may provide a significant symptomatic benefit. PMID- 25126055 TI - Gender differences in the temporal voice areas. AB - There is not only evidence for behavioral differences in voice perception between female and male listeners, but also recent suggestions for differences in neural correlates between genders. The fMRI functional voice localizer (comprising a univariate analysis contrasting stimulation with vocal vs. non-vocal sounds) is known to give robust estimates of the temporal voice areas (TVAs). However, there is growing interest in employing multivariate analysis approaches to fMRI data (e.g., multivariate pattern analysis; MVPA). The aim of the current study was to localize voice-related areas in both female and male listeners and to investigate whether brain maps may differ depending on the gender of the listener. After a univariate analysis, a random effects analysis was performed on female (n = 149) and male (n = 123) listeners and contrasts between them were computed. In addition, MVPA with a whole-brain searchlight approach was implemented and classification maps were entered into a second-level permutation based random effects models using statistical non-parametric mapping (SnPM; Nichols and Holmes, 2002). Gender differences were found only in the MVPA. Identified regions were located in the middle part of the middle temporal gyrus (bilateral) and the middle superior temporal gyrus (right hemisphere). Our results suggest differences in classifier performance between genders in response to the voice localizer with higher classification accuracy from local BOLD signal patterns in several temporal-lobe regions in female listeners. PMID- 25126054 TI - A comprehensive assessment of resting state networks: bidirectional modification of functional integrity in cerebro-cerebellar networks in dementia. AB - In resting state fMRI (rs-fMRI), only functional connectivity (FC) reductions in the default mode network (DMN) are normally reported as a biomarker for Alzheimer's disease (AD). In this investigation we have developed a comprehensive strategy to characterize the FC changes occurring in multiple networks and applied it in a pilot study of subjects with AD and Mild Cognitive Impairment (MCI), compared to healthy controls (HC). Resting state networks (RSNs) were studied in 14 AD (70 +/- 6 years), 12 MCI (74 +/- 6 years), and 16 HC (69 +/- 5 years). RSN alterations were present in almost all the 15 recognized RSNs; overall, 474 voxels presented a reduced FC in MCI and 1244 in AD while 1627 voxels showed an increased FC in MCI and 1711 in AD. The RSNs were then ranked according to the magnitude and extension of FC changes (gFC), putting in evidence 6 RSNs with prominent changes: DMN, frontal cortical network (FCN), lateral visual network (LVN), basal ganglia network (BGN), cerebellar network (CBLN), and the anterior insula network (AIN). Nodes, or hubs, showing alterations common to more than one RSN were mostly localized within the prefrontal cortex and the mesial-temporal cortex. The cerebellum showed a unique behavior where voxels of decreased gFC were only found in AD while a significant gFC increase was only found in MCI. The gFC alterations showed strong correlations (p < 0.001) with psychological scores, in particular Mini-Mental State Examination (MMSE) and attention/memory tasks. In conclusion, this analysis revealed that the DMN was affected by remarkable FC increases, that FC alterations extended over several RSNs, that derangement of functional relationships between multiple areas occurred already in the early stages of dementia. These results warrant future work to verify whether these represent compensatory mechanisms that exploit a pre existing neural reserve through plasticity, which evolve in a state of lack of connectivity between different networks with the worsening of the pathology. PMID- 25126057 TI - Two distinct olfactory bulb sublaminar networks involved in gamma and beta oscillation generation: a CSD study in the anesthetized rat. AB - A prominent feature of olfactory bulb (OB) dynamics is the expression of characteristic local field potential (LFP) rhythms, including a slow respiration related rhythm and two fast alternating oscillatory rhythms, beta (15-30 Hz) and gamma (40-90 Hz). All of these rhythms are implicated in olfactory coding. Fast oscillatory rhythms are known to involve the mitral-granule cell loop. Although the underlying mechanisms of gamma oscillation have been studied, the origin of beta oscillation remains poorly understood. Whether these two different rhythms share the same underlying mechanism is unknown. This study uses a quantitative and detailed current-source density (CSD) analysis combined with multi-unit activity (MUA) recordings to shed light on this question in freely breathing anesthetized rats. In particular, we show that gamma oscillation generation involves mainly the upper half of the external plexiform layer (EPL) and superficial areas of granule cell layer (GRL). In contrast, the generation of beta oscillation involves the lower part of the EPL and deep granule cells. This differential involvement of sublaminar networks is neither dependent on odor quality nor on the precise frequency of the fast oscillation under study. Overall, this study demonstrates a functional sublaminar organization of the rat OB, which is supported by previous anatomical findings. PMID- 25126058 TI - Across-ear stimulus-specific adaptation in the auditory cortex. AB - The ability to detect unexpected or deviant events in natural scenes is critical for survival. In the auditory system, neurons from the midbrain to cortex adapt quickly to repeated stimuli but this adaptation does not fully generalize to other rare stimuli, a phenomenon called stimulus-specific adaptation (SSA). Most studies of SSA were conducted with pure tones of different frequencies, and it is by now well-established that SSA to tone frequency is strong and robust in auditory cortex. Here we tested SSA in the auditory cortex to the ear of stimulation using broadband noise. We show that cortical neurons adapt specifically to the ear of stimulation, and that the contrast between the responses to stimulation of the same ear when rare and when common depends on the binaural interaction class of the neurons. PMID- 25126056 TI - Frontiers in therapeutic development of allopregnanolone for Alzheimer's disease and other neurological disorders. AB - Allopregnanolone (Allo), a neurosteroid, has emerged as a promising promoter of endogenous regeneration in brain. In a mouse model of Alzheimer's disease, Allo induced neurogenesis, oligodendrogenesis, white matter generation and cholesterol homeostasis while simultaneously reducing beta-amyloid and neuroinflammatory burden. Allo activates signaling pathways and gene expression required for regeneration of neural stem cells and their differentiation into neurons. In parallel, Allo activates systems to sustain cholesterol homeostasis and reduce beta-amyloid generation. To advance Allo into studies for chronic human neurological conditions, we examined translational and clinical parameters: dose, regimen, route, formulation, outcome measures, and safety regulations. A treatment regimen of once per week at sub-sedative doses of Allo was optimal for regeneration and reduction in Alzheimer's pathology. This regimen had a high safety profile following chronic exposure in aged normal and Alzheimer's mice. Formulation of Allo for multiple routes of administration has been developed for both preclinical and clinical testing. Preclinical evidence for therapeutic efficacy of Allo spans multiple neurological diseases including Alzheimer's, Parkinson's, multiple sclerosis, Niemann-Pick, diabetic neuropathy, status epilepticus, and traumatic brain injury. To successfully translate Allo as a therapeutic for multiple neurological disorders, it will be necessary to tailor dose and regimen to the targeted therapeutic mechanisms and disease etiology. Treatment paradigms conducted in accelerated disease models in young animals have a low probability of successful translation to chronic diseases in adult and aged humans. Gender, genetic risks, stage and burden of disease are critical determinants of efficacy. This review focuses on recent advances in development of Allo for Alzheimer's disease (AD) that have the potential to accelerate therapeutic translation for multiple unmet neurological needs. PMID- 25126059 TI - The world according to zebrafish: how neural circuits generate behavior. PMID- 25126061 TI - Ethical issues with brain-computer interfaces. PMID- 25126062 TI - Mice with a naturally occurring DISC1 mutation display a broad spectrum of behaviors associated to psychiatric disorders. AB - Disrupted in schizophrenia-1 (DISC1) gene is associated with several neuropsychiatric disorders as it is disrupted by a balanced translocation involving chromosomes 1 and 11 in a large Scottish pedigree with high prevalence of schizophrenia, bipolar disorder and major depression. Since its identification, several mouse models with DISC1 genetic modifications have been generated using different approaches. Interestingly, a natural deletion of 25bp in the 129 mouse strain alters the DISC1 gene reading frame leading to a premature stop codon very close to the gene breakpoint in the mutant allele of the Scottish family. In the present study we confirmed that the 129DISC1(Del) mutation results in reduced level of full length DISC1 in hippocampus of heterozygous mice and we have characterized the behavioral consequences of heterozygous 129DISC1(Del) mutation in a mixed B6129 genetic background. We found alterations in spontaneous locomotor activity (hyperactivity in males and hypoactivity in females), deficits in pre-pulse inhibition (PPI) and also increased despair behavior in heterozygous 129DISC1(Del) mice, thus reproducing typical behaviors associated to psychiatric disorders. Since this mouse strain is widely and commercially available, we propose it as an amenable tool to study DISC1-related biochemical alterations and psychiatric behaviors. PMID- 25126060 TI - Best of both worlds: promise of combining brain stimulation and brain connectome. AB - Transcranial current brain stimulation (tCS) is becoming increasingly popular as a non-pharmacological non-invasive neuromodulatory method that alters cortical excitability by applying weak electrical currents to the scalp via a pair of electrodes. Most applications of this technique have focused on enhancing motor and learning skills, as well as a therapeutic agent in neurological and psychiatric disorders. In these applications, similarly to lesion studies, tCS was used to provide a causal link between a function or behavior and a specific brain region (e.g., primary motor cortex). Nonetheless, complex cognitive functions are known to rely on functionally connected multitude of brain regions with dynamically changing patterns of information flow rather than on isolated areas, which are most commonly targeted in typical tCS experiments. In this review article, we argue in favor of combining tCS method with other neuroimaging techniques (e.g., fMRI, EEG) and by employing state-of-the-art connectivity data analysis techniques (e.g., graph theory) to obtain a deeper understanding of the underlying spatiotemporal dynamics of functional connectivity patterns and cognitive performance. Finally, we discuss the possibilities of using these combined techniques to investigate the neural correlates of human creativity and to enhance creativity. PMID- 25126063 TI - Differential effects of sertraline in a predator exposure animal model of post traumatic stress disorder. AB - Serotonin (5-HT), norepinephrine (NE), and other neurotransmitters are modulated in post-traumatic stress disorder (PTSD). In addition, pro-inflammatory cytokines (PIC) are elevated during the progression of the disorder. Currently, the only approved pharmacologic treatments for PTSD are the selective-serotonin reuptake inhibitors (SSRI) sertraline and paroxetine, but their efficacy in treating PTSD is marginal at best. In combat-related PTSD, SSRIs are of limited effectiveness. Thus, this study sought to analyze the effects of the SSRI sertraline on inflammation and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. We hypothesized that sertraline would diminish inflammatory components and increase 5-HT but might also affect levels of other neurotransmitters, particularly NE. PTSD-like effects were induced in male Sprague-Dawley rats (n = 6/group * 4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1 h on days 1 and 11 of a 31-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, treatment group animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg for 7 consecutive days, while controls received i.p. vehicle. The animals were subsequently sacrificed on day 8. Sertraline attenuated inflammatory markers and normalized 5-HT levels in the central nervous system (CNS). In contrast, sertraline produced elevations in NE in the CNS and systemic circulation of SSRI treated PTSD and control groups. This increase in NE suggests SSRIs produce a heightened noradrenergic response, which might elevate anxiety in a clinical setting. PMID- 25126065 TI - Learning to perceive in the sensorimotor approach: Piaget's theory of equilibration interpreted dynamically. AB - LEARNING TO PERCEIVE IS FACED WITH A CLASSICAL PARADOX: if understanding is required for perception, how can we learn to perceive something new, something we do not yet understand? According to the sensorimotor approach, perception involves mastery of regular sensorimotor co-variations that depend on the agent and the environment, also known as the "laws" of sensorimotor contingencies (SMCs). In this sense, perception involves enacting relevant sensorimotor skills in each situation. It is important for this proposal that such skills can be learned and refined with experience and yet up to this date, the sensorimotor approach has had no explicit theory of perceptual learning. The situation is made more complex if we acknowledge the open-ended nature of human learning. In this paper we propose Piaget's theory of equilibration as a potential candidate to fulfill this role. This theory highlights the importance of intrinsic sensorimotor norms, in terms of the closure of sensorimotor schemes. It also explains how the equilibration of a sensorimotor organization faced with novelty or breakdowns proceeds by re-shaping pre-existing structures in coupling with dynamical regularities of the world. This way learning to perceive is guided by the equilibration of emerging forms of skillful coping with the world. We demonstrate the compatibility between Piaget's theory and the sensorimotor approach by providing a dynamical formalization of equilibration to give an explicit micro-genetic account of sensorimotor learning and, by extension, of how we learn to perceive. This allows us to draw important lessons in the form of general principles for open-ended sensorimotor learning, including the need for an intrinsic normative evaluation by the agent itself. We also explore implications of our micro-genetic account at the personal level. PMID- 25126064 TI - Parallel processing in the brain's visual form system: an fMRI study. AB - We here extend and complement our earlier time-based, magneto-encephalographic (MEG), study of the processing of forms by the visual brain (Shigihara and Zeki, 2013) with a functional magnetic resonance imaging (fMRI) study, in order to better localize the activity produced in early visual areas when subjects view simple geometric stimuli of increasing perceptual complexity (lines, angles, rhombuses) constituted from the same elements (lines). Our results show that all three categories of form activate all three visual areas with which we were principally concerned (V1-V3), with angles producing the strongest and rhombuses the weakest activity in all three. The difference between the activity produced by angles and rhombuses was significant, that between lines and rhombuses was trend significant while that between lines and angles was not. Taken together with our earlier MEG results, the present ones suggest that a parallel strategy is used in processing forms, in addition to the well-documented hierarchical strategy. PMID- 25126066 TI - Different corticospinal control between discrete and rhythmic movement of the ankle. AB - We investigated differences in corticospinal and spinal control between discrete and rhythmic ankle movements. Motor evoked potentials (MEPs) in the tibialis anterior and soleus muscles and soleus H-reflex were elicited in the middle of the plantar flexion phase during discrete ankle movement or in the initial or later cycles of rhythmic ankle movement. The H-reflex was evoked at an intensity eliciting a small M-wave and MEPs were elicited at an intensity of 1.2 times the motor threshold of the soleus MEPs. Only trials in which background EMG level, ankle angle, and ankle velocity were similar among the movement conditions were included for data analysis. In addition, only trials with a similar M-wave were included for data analysis in the experiment evoking H-reflexes. Results showed that H reflex and MEP amplitudes in the soleus muscle during discrete movement were not significantly different from those during rhythmic movement. MEP amplitude in the tibialis anterior muscle during the later cycles of rhythmic movement was significantly larger than that during the initial cycle of the rhythmic movement or during discrete movement. Higher corticospinal excitability in the tibialis anterior muscle during the later cycles of rhythmic movement may reflect changes in corticospinal control from the initial cycle to the later cycles of rhythmic movement. PMID- 25126067 TI - Analysis of sampling artifacts on the Granger causality analysis for topology extraction of neuronal dynamics. AB - Granger causality (GC) is a powerful method for causal inference for time series. In general, the GC value is computed using discrete time series sampled from continuous-time processes with a certain sampling interval length tau, i.e., the GC value is a function of tau. Using the GC analysis for the topology extraction of the simplest integrate-and-fire neuronal network of two neurons, we discuss behaviors of the GC value as a function of tau, which exhibits (i) oscillations, often vanishing at certain finite sampling interval lengths, (ii) the GC vanishes linearly as one uses finer and finer sampling. We show that these sampling effects can occur in both linear and non-linear dynamics: the GC value may vanish in the presence of true causal influence or become non-zero in the absence of causal influence. Without properly taking this issue into account, GC analysis may produce unreliable conclusions about causal influence when applied to empirical data. These sampling artifacts on the GC value greatly complicate the reliability of causal inference using the GC analysis, in general, and the validity of topology reconstruction for networks, in particular. We use idealized linear models to illustrate possible mechanisms underlying these phenomena and to gain insight into the general spectral structures that give rise to these sampling effects. Finally, we present an approach to circumvent these sampling artifacts to obtain reliable GC values. PMID- 25126068 TI - Ventral-stream-like shape representation: from pixel intensity values to trainable object-selective COSFIRE models. AB - The remarkable abilities of the primate visual system have inspired the construction of computational models of some visual neurons. We propose a trainable hierarchical object recognition model, which we call S-COSFIRE (S stands for Shape and COSFIRE stands for Combination Of Shifted FIlter REsponses) and use it to localize and recognize objects of interests embedded in complex scenes. It is inspired by the visual processing in the ventral stream (V1/V2 -> V4 -> TEO). Recognition and localization of objects embedded in complex scenes is important for many computer vision applications. Most existing methods require prior segmentation of the objects from the background which on its turn requires recognition. An S-COSFIRE filter is automatically configured to be selective for an arrangement of contour-based features that belong to a prototype shape specified by an example. The configuration comprises selecting relevant vertex detectors and determining certain blur and shift parameters. The response is computed as the weighted geometric mean of the blurred and shifted responses of the selected vertex detectors. S-COSFIRE filters share similar properties with some neurons in inferotemporal cortex, which provided inspiration for this work. We demonstrate the effectiveness of S-COSFIRE filters in two applications: letter and keyword spotting in handwritten manuscripts and object spotting in complex scenes for the computer vision system of a domestic robot. S-COSFIRE filters are effective to recognize and localize (deformable) objects in images of complex scenes without requiring prior segmentation. They are versatile trainable shape detectors, conceptually simple and easy to implement. The presented hierarchical shape representation contributes to a better understanding of the brain and to more robust computer vision algorithms. PMID- 25126069 TI - Pydpiper: a flexible toolkit for constructing novel registration pipelines. AB - Using neuroimaging technologies to elucidate the relationship between genotype and phenotype and brain and behavior will be a key contribution to biomedical research in the twenty-first century. Among the many methods for analyzing neuroimaging data, image registration deserves particular attention due to its wide range of applications. Finding strategies to register together many images and analyze the differences between them can be a challenge, particularly given that different experimental designs require different registration strategies. Moreover, writing software that can handle different types of image registration pipelines in a flexible, reusable and extensible way can be challenging. In response to this challenge, we have created Pydpiper, a neuroimaging registration toolkit written in Python. Pydpiper is an open-source, freely available software package that provides multiple modules for various image registration applications. Pydpiper offers five key innovations. Specifically: (1) a robust file handling class that allows access to outputs from all stages of registration at any point in the pipeline; (2) the ability of the framework to eliminate duplicate stages; (3) reusable, easy to subclass modules; (4) a development toolkit written for non-developers; (5) four complete applications that run complex image registration pipelines "out-of-the-box." In this paper, we will discuss both the general Pydpiper framework and the various ways in which component modules can be pieced together to easily create new registration pipelines. This will include a discussion of the core principles motivating code development and a comparison of Pydpiper with other available toolkits. We also provide a comprehensive, line-by-line example to orient users with limited programming knowledge and highlight some of the most useful features of Pydpiper. In addition, we will present the four current applications of the code. PMID- 25126070 TI - An intraductal papillary neoplasm of the bile duct at the duodenal papilla. AB - In recent years, the disease concept of intraductal papillary neoplasm of the bile duct (IPNB) has been attracting attention as a biliary lesion that is morphologically similar to intraductal papillary mucinous neoplasm (IPMN), which is considered to be a counterpart of IPMN. However, there are few reports on IPNB, and a consensus regarding the features of this disease is thus lacking. We experienced an extremely rare case of IPNB occurring in the bile duct at the duodenal papilla, which is a tumor presentation that has not previously been reported. Herein, we report this interesting case and discuss the possible association between IPMN and IPNB. PMID- 25126071 TI - Asymptomatic pelvic metastasis from thymic carcinoma: a case report. AB - Thymic epithelial tumors are rare and often occur somewhere local. Metastatic sites of thymic carcinomas (Masaoka-Koga stage IVb) are mostly seen in the lung, liver and brain. We report a 64-year-old female with an initial diagnosis of thymoma B3 who first showed thoracic recurrences and then an asymptomatic isolated pelvic metastasis from her thymic carcinoma. PMID- 25126072 TI - A Report of Disseminated Carcinomatosis of the Bone Marrow Originating from Transverse Colon Cancer Successfully Treated with Chemotherapy Using XELOX plus Bevacizumab. AB - A 61-year-old male, who had been admitted to another hospital due to disseminated intravascular coagulation (DIC), was referred to our hospital. Total colonoscopy, abdominal dynamic CT and positron-emission tomography revealed bone metastasis and multiple lymphocytic metastases from transverse colon cancer in addition to disseminated carcinomatosis of the bone marrow (DCBM). We immediately performed chemotherapy with XELOX + bevacizumab and denosumab against DCBM from transverse colon cancer in order to avoid radical surgery. In addition, we initiated the administration of recombinant human soluble thrombomodulin for 1 week to treat DIC. The patient was able to tolerate and receive 4 cycles of chemotherapy without any severe side effects. After receiving the 4 cycles of treatment, he recovered from DIC, and the bone and multiple lymphocytic metastases disappeared. PMID- 25126074 TI - Repeat Descemetopexy after Descemet's Membrane Detachment following Phacoemulsification. AB - Descemet's membrane detachment (DMD) is an uncommon condition with a wide range of possible etiologies. Probably the commonest cause is a localized detachment occurring after cataract extraction surgery. Descemetopexy gives good anatomic attachment rates and visual outcomes and has become the standard treatment for DMD. However, in cases with failed initial descemetopexy, the next step in the management of such cases remains unclear. Before initiating a complex surgical procedure like keratoplasty, which requires good postoperative care and regular follow-ups, repeat descemetopexy with a long-term tamponade using 14% C3F8 gas for recurrent DMD is definitely a worthwhile attempt. PMID- 25126075 TI - Hemorrhagic macular infarction after intravitreal bevacizumab for chronic multifocal central serous chorioretinopathy. AB - We hereby report a case of hemorrhagic macular infarction after intravitreal bevacizumab for chronic multifocal central serous chorioretinopathy (CSC). Issues regarding safety and adverse effects of bevacizumab are discussed. To the best of our knowledge, this is the first reported case of hemorrhagic macular infarction after intravitreal bevacizumab for chronic multifocal CSC. PMID- 25126073 TI - A Prospective Phase I/II Study: Combination Chemotherapy with Docetaxel and Pemetrexed as Second-Line Treatment in Patients with Stage IIIB/IV Non-Small Cell Lung Cancer. AB - INTRODUCTION: Two standard single-agent chemotherapy treatments (docetaxel and pemetrexed) were combined in this trial and administered as second-line treatment in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and feasibility of combining docetaxel with pemetrexed. METHODS: Six patients were enrolled between August 2007 and March 2009 with stage IIIB/IV NSCLC. The dose-escalation model included a pemetrexed infusion on day 1 of 200-300 mg/m(2) followed by infusion of docetaxel on days 1, 8 and 15 at doses from 20 to 30 mg/m(2). Primary study endpoints included efficacy and safety variables, also progression-free, overall and 1-year survival and time to progression. RESULTS: The study was abandoned due to adverse effects defined in the protocol. The major toxicities were all of grade 3 and included fatigue, stomatitis/mucositis, diarrhea and in one case, an episode of febrile neutropenia. Two patients died during the study, but not as a direct result of the treatment. CONCLUSIONS: We recommend that docetaxel or pemetrexed monotherapies should continue to be considered the standard second-line chemotherapy treatment against NSCLC. The results of this study warrant no further investigation into this particular combination treatment due to the severe toxicity effects encountered. PMID- 25126076 TI - Haptic breakage after transscleral fixation of a single-piece acrylic intraocular lens. AB - PURPOSE: To report the case of a patient with a damaged haptic of an acrylic intraocular lens (IOL) after transscleral IOL fixation. METHODS: This is a retrospective and descriptive case report. RESULTS: A 40-year-old man presented with sudden visual loss in the left eye. He had undergone phacoemulsification/aspiration and IOL implantation 3 years previously and IOL repositioning with transscleral fixation 2 years before the initial visit. His visual acuity was 0.3 in the left eye due to corneal edema caused by a foreign body, i.e., the severed haptic tip of the single-piece acrylic IOL, which was surgically removed. The IOL itself was tilted and therefore explanted. The surface of the tip of the haptic suggested that the monofilament suture thread had exerted continuous force across the haptic. CONCLUSIONS: The haptics of acrylic IOLs can be damaged after transscleral fixation. PMID- 25126077 TI - A new clinical tool for assessing numerical abilities in neurological diseases: numerical activities of daily living. AB - The aim of this study was to build an instrument, the numerical activities of daily living (NADL), designed to identify the specific impairments in numerical functions that may cause problems in everyday life. These impairments go beyond what can be inferred from the available scales evaluating activities of daily living in general, and are not adequately captured by measures of the general deterioration of cognitive functions as assessed by standard clinical instruments like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group affected by a wide variety of neurological conditions (n = 175), with NADL along with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory construct validity and reliability, across a wide age range. This enabled us to calculate appropriate criteria for impairment that took into account age and education. It was found that neurological patients tended to overestimate their abilities as compared to the judgment made by their caregivers, assessed with objective tests of numerical abilities. PMID- 25126078 TI - Lithium suppresses Abeta pathology by inhibiting translation in an adult Drosophila model of Alzheimer's disease. AB - The greatest risk factor for Alzheimer's disease (AD) is age, and changes in the ageing nervous system are likely contributors to AD pathology. Amyloid beta (Abeta) accumulation, which occurs as a result of the amyloidogenic processing of amyloid precursor protein (APP), is thought to initiate the pathogenesis of AD, eventually leading to neuronal cell death. Previously, we developed an adult onset Drosophila model of AD. Mutant Abeta42 accumulation led to increased mortality and neuronal dysfunction in the adult flies. Furthermore, we showed that lithium reduced Abeta42 protein, but not mRNA, and was able to rescue Abeta42-induced toxicity. In the current study, we investigated the mechanism/s by which lithium modulates Abeta42 protein levels and Abeta42 induced toxicity in the fly model. We found that lithium caused a reduction in protein synthesis in Drosophila and hence the level of Abeta42. At both the low and high doses tested, lithium rescued the locomotory defects induced by Abeta42, but it rescued lifespan only at lower doses, suggesting that long-term, high-dose lithium treatment may have induced toxicity. Lithium also down-regulated translation in the fission yeast Schizosaccharomyces pombe associated with increased chronological lifespan. Our data highlight a role for lithium and reduced protein synthesis as potential therapeutic targets for AD pathogenesis. PMID- 25126079 TI - RNA Transcription and Maturation in Skeletal Muscle Cells are Similarly Impaired in Myotonic Dystrophy and Sarcopenia: The Ultrastructural Evidence. PMID- 25126080 TI - Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labor. AB - BACKGROUND: Human labor is a complex series of cellular and molecular events that occur at the materno-fetal and uterine levels. Many hypotheses have been proposed for the initiation of human labor, one hypothesis suggests that maturation of the fetus releases a signal in the amniotic fluid that will be transmitted to myometrium via the fetal membranes and initiate uterine contractions. There is strong evidence that prostaglandins (PGs) play a central role in initiation and progression of human labor. OBJECTIVES: In this study we intended to investigate the expression of prostaglandin F synthase and the prostaglandin transporter in the human fetal membranes and to explore the relationship between cytokines and PGs in the mechanism of human labor. METHODS: We used fetal membranes obtained before labor at term and after spontaneous labor at term or preterm to identify the changes in prostaglandin F synthase (AKR1B1) and human prostaglandin transporter (SLCO2A1) proteins in relation to parturition. Using fetal membranes explants we tested the effect of cytokines (interleukin-1 and tumor necrosis factor alpha) on PG production and the concomitant changes in cyclooxygenase-2 (PTGS2), AKR1B1 and SLCO2A1 expression. RESULTS: Expression of PTGS2 and AKR1B1 was upregulated in the fetal membranes in association with term labor while SLCO2A1 was downregulated with advancing gestation and during term labor. Before labor, IL-1 increased the expression of PTGS2, however during labor TNF upregulated PTGS2 and AKR1B1 proteins. CONCLUSIONS: The prostaglandin F synthase AKR1B1 is upregulated while prostaglandin transporter is downregulated during term labor. The amnion is more responsive than choriodecidua to stimulation with pro-inflammatory cytokines. The mechanisms of term and preterm labor are different. PMID- 25126081 TI - Waves of visibility: probing the depth of inter-ocular suppression with transient and sustained targets. AB - In order to study non-conscious visual processing, researchers render otherwise consciously perceived images into invisible stimuli. Through the years, several psychophysical techniques have been developed for this purpose. Yet the comparison of experimental results across techniques remains a difficult task as the depth of suppression depends on the interactions between the type of stimuli and the suppression methods employed. This poses a limit to the inferences that researchers make about the extent of non-conscious processes. We investigated the mechanisms underlying inter-ocular suppression during continuous flash suppression (CFS) and dichoptic visual masking using a transient onset target stimulus and a variety of stimulus/mask temporal manipulations. We show that target duration, timing of target onset, and mask frequency are key aspects of inter-ocular suppression during CFS with transient targets. The differences between our results and sustained target CFS studies suggest that two distinct mechanisms are involved in the detection of transient and prolonged target stimuli during CFS. Our results provide insight into the dynamics of CFS together with evidence for similarities between transient target CFS and dichoptic visual masking. PMID- 25126082 TI - The cortical microstructural basis of lateralized cognition: a review. AB - The presence of asymmetry in the human cerebral hemispheres is detectable at both the macroscopic and microscopic scales. The horizontal expansion of cortical surface during development (within individual brains), and across evolutionary time (between species), is largely due to the proliferation and spacing of the microscopic vertical columns of cells that form the cortex. In the asymmetric planum temporale (PT), minicolumn width asymmetry is associated with surface area asymmetry. Although the human minicolumn asymmetry is not large, it is estimated to account for a surface area asymmetry of approximately 9% of the region's size. Critically, this asymmetry of minicolumns is absent in the equivalent areas of the brains of other apes. The left-hemisphere dominance for processing speech is thought to depend, partly, on a bias for higher resolution processing across widely spaced minicolumns with less overlapping dendritic fields, whereas dense minicolumn spacing in the right hemisphere is associated with more overlapping, lower resolution, holistic processing. This concept refines the simple notion that a larger brain area is associated with dominance for a function and offers an alternative explanation associated with "processing type." This account is mechanistic in the sense that it offers a mechanism whereby asymmetrical components of structure are related to specific functional biases yielding testable predictions, rather than the generalization that "bigger is better" for any given function. Face processing provides a test case - it is the opposite of language, being dominant in the right hemisphere. Consistent with the bias for holistic, configural processing of faces, the minicolumns in the right-hemisphere fusiform gyrus are thinner than in the left hemisphere, which is associated with featural processing. Again, this asymmetry is not found in chimpanzees. The difference between hemispheres may also be seen in terms of processing speed, facilitated by asymmetric myelination of white matter tracts (Anderson et al., 1999 found that axons of the left posterior superior temporal lobe were more thickly myelinated). By cross-referencing the differences between the active fields of the two hemispheres, via tracts such as the corpus callosum, the relationship of local features to global features may be encoded. The emergent hierarchy of features within features is a recursive structure that may functionally contribute to generativity - the ability to perceive and express layers of structure and their relations to each other. The inference is that recursive generativity, an essential component of language, reflects an interaction between processing biases that may be traceable in the microstructure of the cerebral cortex. Minicolumn organization in the PT and the prefrontal cortex has been found to correlate with cognitive scores in humans. Altered minicolumn organization is also observed in neuropsychiatric disorders including autism and schizophrenia. Indeed, altered interhemispheric connections correlated with minicolumn asymmetry in schizophrenia may relate to language-processing anomalies that occur in the disorder. Schizophrenia is associated with over interpretation of word meaning at the semantic level and over-interpretation of relevance at the level of pragmatic competence, whereas autism is associated with overly literal interpretation of word meaning and under-interpretation of social relevance at the pragmatic level. Both appear to emerge from a disruption of the ability to interpret layers of meaning and their relations to each other. This may be a consequence of disequilibrium in the processing of local and global features related to disorganization of minicolumnar units of processing. PMID- 25126083 TI - Publication bias and the limited strength model of self-control: has the evidence for ego depletion been overestimated? AB - Few models of self-control have generated as much scientific interest as has the limited strength model. One of the entailments of this model, the depletion effect, is the expectation that acts of self-control will be less effective when they follow prior acts of self-control. Results from a previous meta-analysis concluded that the depletion effect is robust and medium in magnitude (d = 0.62). However, when we applied methods for estimating and correcting for small-study effects (such as publication bias) to the data from this previous meta-analysis effort, we found very strong signals of publication bias, along with an indication that the depletion effect is actually no different from zero. We conclude that until greater certainty about the size of the depletion effect can be established, circumspection about the existence of this phenomenon is warranted, and that rather than elaborating on the model, research efforts should focus on establishing whether the basic effect exists. We argue that the evidence for the depletion effect is a useful case study for illustrating the dangers of small-study effects as well as some of the possible tools for mitigating their influence in psychological science. PMID- 25126084 TI - "Not in their right mind": the relation of psychopathology to the quantity and quality of creative thought. AB - The empirical link between psychopathology and creativity is often correlational and fraught with suspiciously causal interpretations. In this paper, we review research in favor of the position that certain forms of psychopathology that profoundly affect the neural substrates for rule-based thought (e.g., schizophrenia, bipolar disorder) can significantly influence the quantity of creative production. Because highly productive individuals, irrespective of psychopathology, often produce work of greater quality, it seems that such an increase in the quantity of one's output positively affects the likelihood of generating those statistically rare acts and achievements identified and celebrated as creative. We consider evidence that offers support for such a claim. In addition, we explore findings from neuroscience that can address how a neural mechanism, the flexibility of which relies on tradeoffs between rule-based (e.g., prefrontal cortex) and stimulus-based (e.g., sensorimotor cortex) brain regions, is influenced by psychopathology in ways that can alter dramatically the quantity and quality of creative output. PMID- 25126086 TI - The role of the immune system in the pathogenesis of diabetic complications. PMID- 25126085 TI - How Much Should We Weigh for a Long and Healthy Life Span? The Need to Reconcile Caloric Restriction versus Longevity with Body Mass Index versus Mortality Data. AB - Total caloric restriction (CR) without malnutrition is a well-established experimental approach to extend life span in laboratory animals. Although CR in humans is capable of shifting several endocrinological parameters, it is not clear where the minimum inflection point of the U-shaped curve linking body mass index (BMI) with all-cause mortality lies. The exact trend of this curve, when used for planning preventive strategies for public health is of extreme importance. Normal BMI ranges from 18.5 to 24.9; many epidemiological studies show an inverse relationship between mortality and BMI inside the normal BMI range. Other studies show that the lowest mortality in the entire range of BMI is obtained in the overweight range (25-29.9). Reconciling the extension of life span in laboratory animals by experimental CR with the BMI-mortality curve of human epidemiology is not trivial. In fact, one interpretation is that the CR data are identifying a known: "excess fat is deleterious for health"; although a second interpretation may be that: "additional leanness from a normal body weight may add health and life span delaying the process of aging." This short review hope to start a discussion aimed at finding the widest consensus on which weight range should be considered the "healthiest" for our species, contributing in this way to the picture of what is the correct life style for a long and healthy life span. PMID- 25126088 TI - Invited commentary: lubricating the rusty wheel, new insights into iron oxidizing bacteria through comparative genomics. PMID- 25126090 TI - Nitrate transporters in leaves and their potential roles in foliar uptake of nitrogen dioxide. AB - While plant roots are specialized organs for the uptake and transport of water and nutrients, the absorption of gaseous or liquid mineral elements by aerial plant parts has been recognized since more than one century. Nitrogen (N) is an essential macronutrient which generally absorbed either as nitrate (NO(-) 3) or ammonium (NH(+) 4) by plant roots. Gaseous nitrogen pollutants like N dioxide (NO2) can also be absorbed by plant surfaces and assimilated via the NO(-) 3 assimilation pathway. The subsequent NO(-) 3 flux may induce or repress the expression of various NO(-) 3-responsive genes encoding for instance, the transmembrane transporters, NO(-) 3/NO(-) 2 (nitrite) reductase, or assimilatory enzymes involved in N metabolism. Based on the existing information, the aim of this review was to theoretically analyze the potential link between foliar NO2 absorption and N transport and metabolism. For such purpose, an overview of the state of knowledge on the NO(-) 3 transporter genes identified in leaves or shoots of various species and their roles for NO(-) 3 transport across the tonoplast and plasma membrane, in addition to the process of phloem loading is briefly provided. It is assumed that a NO2-induced accumulation of NO(-) 3/NO(-) 2 may alter the expression of such genes, hence linking transmembrane NO(-) 3 transporters and foliar uptake of NO2. It is likely that NRT1/NRT2 gene expression and species-dependent apoplastic buffer capacity may be also related to the species-specific foliar NO2 uptake process. It is concluded that further work focusing on the expression of NRT1 (NRT1.1, NRT1.7, NRT1.11, and NRT1.12), NRT2 (NRT2.1, NRT2.4, and NRT2.5) and chloride channel family genes (CLCa and CLCd) may help us elucidate the physiological and metabolic response of plants fumigated with NO2. PMID- 25126089 TI - Clearance of Apoptotic Bodies, NETs, and Biofilm DNA: Implications for Autoimmunity. PMID- 25126091 TI - Next generation sequencing technologies for next generation plant breeding. PMID- 25126087 TI - Podocyte pathology and nephropathy - sphingolipids in glomerular diseases. AB - Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick, and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarly, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD), HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS), and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine, and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is expressed in podocytes where it modulates acid sphingomyelinase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed. PMID- 25126093 TI - Molecular targets of chromatin repressive mark H3K9me3 in primate progenitor cells within adult neurogenic niches. AB - Histone 3 Lysine 9 (H3K9) methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3) is enriched in an adult neural stem cell niche- the subventricular zone (SVZ) on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep sequencing) and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche. PMID- 25126094 TI - Does the Implant Surgical Technique Affect the Primary and/or Secondary Stability of Dental Implants? A Systematic Review. AB - Background. A number of surgical techniques for implant site preparation have been advocated to enhance the implant of primary and secondary stability. However, there is insufficient scientific evidence to support the association between the surgical technique and implant stability. Purpose. This review aimed to investigate the influence of different surgical techniques including the undersized drilling, the osteotome, the piezosurgery, the flapless procedure, and the bone stimulation by low-level laser therapy on the primary and/or secondary stability of dental implants. Materials and methods. A search of PubMed, Cochrane Library, and grey literature was performed. The inclusion criteria comprised observational clinical studies and randomized controlled trials (RCTs) conducted in patients who received dental implants for rehabilitation, studies that evaluated the association between the surgical technique and the implant primary and/or secondary stability. The articles selected were carefully read and classified as low, moderate, and high methodological quality and data of interest were tabulated. Results. Eight clinical studies were included then they were classified as moderate or high methodological quality and control of bias. Conclusions. There is a weak evidence suggesting that any of previously mentioned surgical techniques could influence the primary and/or secondary implant stability. PMID- 25126095 TI - Successful management of coronary artery rupture with stent-graft: a case report. AB - Perforation of coronary arteries is a relatively rare yet life-threatening complication of percutaneus coronary interventions and is encountered in approximately 0.5% of these procedures. According to the type of coronary perforation, various methods of correction are employed, ranging from conservative approach to emergency cardiac surgery. Coronary stent-grafts are composed of two metal stents and a polytetrafluoroethylene layer between them. Advent of such stents enabled efficient endovascular repair of coronary artery perforation. We present a case of coronary artery perforation which had occurred during stent implantation for the treatment of a bridged segment in the distal portion of the left anterior descending artery. This perforation was successfully managed by implanting a stent-graft. PMID- 25126096 TI - Acute abdominal pain after intercourse: adrenal hemorrhage as the first sign of metastatic lung cancer. AB - Although the adrenal glands are a common site of cancer metastases, they are often asymptomatic and discovered incidentally on CT scan or autopsy. Spontaneous adrenal hemorrhage associated with metastatic lung cancer is an exceedingly rare phenomenon, and diagnosis can be difficult due to its nonspecific symptoms and ability to mimic other intra-abdominal pathologies. We report a case of a 65-year old man with a history of right upper lobectomy seven months earlier for stage IB non-small cell lung cancer who presented with acute abdominal pain after intercourse. CT scan revealed a new right adrenal mass with surrounding hemorrhage, and subsequent FDG-PET scan confirmed new metabolic adrenal metastases. The patient's presentation of abdominal pain and adrenal hemorrhage immediately after sexual intercourse suggests that exertion, straining, or increased intra-abdominal pressure might be risk factors for precipitation of hemorrhage in patients with adrenal metastases. Management includes pain control and supportive treatment in mild cases, with arterial embolization or adrenalectomy being reserved for cases of severe hemorrhage. PMID- 25126092 TI - Unraveling plant hormone signaling through the use of small molecules. AB - Plants have acquired the capacity to grow continuously and adjust their morphology in response to endogenous and external signals, leading to a high architectural plasticity. The dynamic and differential distribution of phytohormones is an essential factor in these developmental changes. Phytohormone perception is a fast but complex process modulating specific developmental reprogramming. In recent years, chemical genomics or the use of small molecules to modulate target protein function has emerged as a powerful strategy to study complex biological processes in plants such as hormone signaling. Small molecules can be applied in a conditional, dose-dependent and reversible manner, with the advantage of circumventing the limitations of lethality and functional redundancy inherent to traditional mutant screens. High-throughput screening of diverse chemical libraries has led to the identification of bioactive molecules able to induce plant hormone-related phenotypes. Characterization of the cognate targets and pathways of those molecules has allowed the identification of novel regulatory components, providing new insights into the molecular mechanisms of plant hormone signaling. An extensive structure-activity relationship (SAR) analysis of the natural phytohormones, their designed synthetic analogs and newly identified bioactive molecules has led to the determination of the structural requirements essential for their bioactivity. In this review, we will summarize the so far identified small molecules and their structural variants targeting specific phytohormone signaling pathways. We will highlight how the SAR analyses have enabled better interrogation of the molecular mechanisms of phytohormone responses. Finally, we will discuss how labeled/tagged hormone analogs can be exploited, as compelling tools to better understand hormone signaling and transport mechanisms. PMID- 25126097 TI - One-year prevalence, comorbidities and cost of cachexia-related inpatient admissions in the USA. AB - BACKGROUND: Cachexia is a condition characterized as a loss in body mass or metabolic dysfunction and is associated with several prevalent chronic health conditions including many cancers, COPD, HIV, and kidney disease, with between 10 and 50% of patients with these conditions having cachexia. Currently there is little research into cachexia and our objective is to characterize cachexia patients, their healthcare utilization, and associated hospitalization costs. Given the increasing prevalence of chronic diseases, it is important to better understand cachexia so that the condition can be better diagnosed and managed. METHODS: We utilized one year (2009) of the Nationwide Inpatient Sample (NIS). The NIS represents all inpatient stays at a random 20% sample of all hospitals within the United States. We grouped cachexia individuals by primary or secondary discharge diagnosis and then compared those with cachexia to all others in terms of length of stay (LOS) and total cost. Finally we looked into factors predicting increased LOS using a negative binomial model. RESULTS: We estimated US prevalence for cachexia-related inpatient admissions at 161,898 cases. Cachexia patients were older, with an average age of 67.95 versus 48.10 years in their non cachexia peers. Hospitalizations associated with cachexia had an increased LOS compared to non-cachexia patients (6 versus 3 days), with average costs per stay $4641.30 greater. Differences were seen in loss of function (LOF) with cachexia patients, mostly in the major LOF category (52.60%), whereas non-cachexia patients were spread between minor, moderate, and major LOF (36.28%, 36.11%, and 21.26%, respectively). Significant positive predictors of increased LOS among cachexia patients included urban hospital (IRR=1.21, non-teaching urban; IRR=1.23, teaching urban), having either major (IRR=1.41) or extreme (IRR=2.64) LOF, and having a primary diagnosis of pneumonia (IRR=1.15). CONCLUSION: We have characterized cachexia and seen it associated with increased length of stay, increased cost, and more severe loss of function in patients compared to those without cachexia. PMID- 25126098 TI - Retrospective long-term comparison of naturopathic fasting therapy and weight reduction diet in overweight patients. AB - In a follow-up study overweight and obese patients fasting according to Buchinger (modified) and a control group treated by a weight reduction diet in the context of an inpatient naturopathic complex treatment were compared using a questionnaire developed for a standardized phone interview 6.8 +/- 1.1 years after inpatient treatment. During the inpatient treatment the fasting patients significantly more body weight, but at the time of the interview significantly more weight was gained again. 10.7% of the fasting patients and 31.9% of the control group lowered their weight at least 5% of their initial weight up to the interview. 42% of the fasting and 74% of the control group persistently changed their diet. The control group followed a significantly higher number of trained nutritional aspects. 21% of the fasting and 40% of the control group increased their leisure activity permanently. Continued improvement in quality of life was achieved by 16% of the fasting patients and 28% of the control group. The fasting therapy, carried out as part of the inpatient naturopathic complex treatment, turned out to be less suitable for the treatment of overweight and obesity compared to standard therapy. One likely determinant is the minor poststationary lifestyle modification. PMID- 25126100 TI - Buyang huanwu decoction for healthcare: evidence-based theoretical interpretations of treating different diseases with the same method and target of vascularity. AB - Buyang Huanwu Decoction (BHD) is a famous herbal prescription that has been used to treat stroke for centuries. Recent studies reported that the use of BHD had been extended to treat various kinds of disorders according to the TCM syndrome theory of Treating Different Diseases with the Same Method (TDDSM). Here, an overview of systematic reviews (SRs) of BHD for healthcare was conducted to interpret the TCM theory of TDDSM and its target of vascularity in an evidence based manner. Literature searches were carried out in 5 databases to search SRs of BHD for any indication up to August 2013. Thirteen eligible SRs were identified which reported a wide range of vascular conditions. Based on the Overview Quality Assessment Questionnaire scores, the quality of included SRs was varied, with an average score of 4 points. We found that there is premature evidence for the use of BHD for healthcare, whereas BHD was well tolerable in all patients. BHD can be used to treat many disorders with the same therapeutic principle of invigorating Qi to activate blood circulation, which is essentially a manifestation of the TDDSM and is likely to account for targeting the specific pathogenesis of vascular diseases. PMID- 25126101 TI - A unique electrical thermal stimulation system comparable to moxibustion of subcutaneous tissue. AB - Moxibustion strengthens immunity and it is an effective treatment modality, but, depending on the material quantity, shape, and composition, the thermal strength and intensity can be difficult to control, which may cause pain or epidermal burns. To overcome these limitations, a heat stimulating system which is able to control the thermal intensity was developed. The temperature distributions on epidermis, at 5 mm and 10 mm of depth, in rabbit femoral tissue were compared between moxibustion and the electric thermal stimulation system. The stimulation system consists of a high radio frequency dielectric heating equipment (2 MHz frequency, maximum power 200 W), isolation probe, isolation plate, negative pressure generator, and a temperature assessment system. The temperature was modulated by controlling the stimulation pulse duty ratio, repetition number, and output. There were 95% and 91% temperature distribution correlations between moxibustion and the thermal stimulus at 5 mm and 10 mm of depth in tissue, respectively. Moreover, the epidermal temperature in thermal stimulation was lower than that in moxibustion. These results showed that heat loss by the electric thermal stimulation system is less than that by the traditional moxibustion method. Furthermore, the proposed electric thermal stimulation did not cause adverse effects, such as suppuration or blisters, and also provided subcutaneous stimulation comparable to moxibustion. PMID- 25126099 TI - Antileishmanial activity of medicinal plants used in endemic areas in northeastern Brazil. AB - This study investigates the leishmanicidal activity of five species of plants used in folk medicine in endemic areas of the state of Alagoas, Brazil. Data were collected in the cities of Colonia Leopoldina, Novo Lino, and Uniao dos Palmares, Alagoas state, from patients with cutaneous leishmaniasis (Leishmania amazonensis) who use medicinal plants to treat this disease. Plants extracts were tested at a concentration of 1-100 MUg/mL in all experiments, except in an assay to evaluate activity against amastigotes, when 10 MUg/mL was used. All plants extracts did not show deleterious activity to the host cell evidenced by LDH assay at 100, 10, and 1 MUg/mL after 48 h of incubation. The plants extracts Hyptis pectinata (L.) Poit, Aloe vera L., Ruta graveolens L., Pfaffia glomerata (Spreng.) Pedersen, and Chenopodium ambrosioides L. exhibited direct activity against extracellular forms at 100 MUg/mL; these extracts inhibited growth by 81.9%, 82.9%, 74.4%, 88.7%, and 87.4%, respectively, when compared with promastigotes. The plants extracts H. pectinata, A. vera, and R. graveolens also significantly diminished the number of amastigotes at 10 MUg/mL, inhibiting growth by 85.0%, 40.4%, 94.2%, and 97.4%, respectively, when compared with control. Based on these data, we conclude that the five plants exhibited considerable leishmanicidal activity. PMID- 25126102 TI - Neurotrophic Signaling Factors in Brain Ischemia/Reperfusion Rats: Differential Modulation Pattern between Single-Time and Multiple Electroacupuncture Stimulation. AB - Electroacupuncture (EA) treatment has been widely used for stroke-like disorders in traditional Chinese medicine. However, the underlying mechanisms remain unclear. Our previous studies showed that single-time EA stimulation at "Baihui" (GV 20) and "Shuigou" (GV 26) after the onset of ischemia can protect the brain against ischemic injury in rats with middle cerebral artery occlusion (MCAO). Here, we further investigated the differential effects between multiple EA and single-time EA stimulation on ischemic injury. In the present study, we found that both single-time EA and multiple EA stimulation significantly reduced MCAO induced ischemic infarction, while only multiple EA attenuated sensorimotor dysfunctions. Also, with PCR array screening and ingenuity gene analysis, we revealed that multiple EA and single-time EA stimulation could differentially induce expression changes in neurotrophic signaling related genes. Meanwhile, with western blotting, we demonstrated that the level of glia maturation factor beta (GMFbeta) increased in the early stage (day 1) of reperfusion, and this upregulation was suppressed only by single-time EA stimulation. These findings suggest that the short-term effect of single-time EA stimulation differs from the cumulative effect of multiple EA, which possibly depends on their differential modulation on neurotrophic signaling molecules expression. PMID- 25126103 TI - A novel nonparametric item response theory approach to measuring socioeconomic position: a comparison using household expenditure data from a Vietnam health survey, 2003. AB - BACKGROUND: Measures of household socio-economic position (SEP) are widely used in health research. There exist a number of approaches to their measurement, with Principal Components Analysis (PCA) applied to a basket of household assets being one of the most common. PCA, however, carries a number of assumptions about the distribution of the data which may be untenable, and alternative, non-parametric, approaches may be preferred. Mokken scale analysis is a non-parametric, item response theory approach to scale development which appears never to have been applied to household asset data. A Mokken scale can be used to rank order items (measures of wealth) as well as households. Using data on household asset ownership from a national sample of 4,154 consenting households in the World Health Survey from Vietnam, 2003, we construct two measures of household SEP. Seventeen items asking about assets, and utility and infrastructure use were used. Mokken Scaling and PCA were applied to the data. A single item measure of total household expenditure is used as a point of contrast. RESULTS: An 11 item scale, out of the 17 items, was identified that conformed to the assumptions of a Mokken Scale. All the items in the scale were identified as strong items (Hi > .5). Two PCA measures of SEP were developed as a point of contrast. One PCA measure was developed using all 17 available asset items, the other used the reduced set of 11 items identified in the Mokken scale analaysis. The Mokken Scale measure of SEP and the 17 item PCA measure had a very high correlation (r = .98), and they both correlated moderately with total household expenditure: r = .59 and r = .57 respectively. In contrast the 11 item PCA measure correlated moderately with the Mokken scale (r = .68), and weakly with the total household expenditure (r = .18). CONCLUSION: The Mokken scale measure of household SEP performed at least as well as PCA, and outperformed the PCA measure developed with the 11 items used in the Mokken scale. Unlike PCA, Mokken scaling carries no assumptions about the underlying shape of the distribution of the data, and can be used simultaneous to order household SEP and items. The approach, however, has not been tested with data from other countries and remains an interesting, but under researched approach. PMID- 25126104 TI - Returning findings within longitudinal cohort studies: the 1958 birth cohort as an exemplar. AB - Population-based, prospective longitudinal cohort studies are considering the issues surrounding returning findings to individuals as a result of genomic and other medical research studies. While guidance is being developed for clinical settings, the process is less clear for those conducting longitudinal research. This paper discusses work conducted on behalf of The UK Cohort and Longitudinal Study Enhancement Resource programme (CLOSER) to examine consent requirements, process considerations and specific examples of potential findings in the context of the 1958 British Birth cohort. Beyond deciding which findings to return, there are questions of whether re-consent is needed and the possible impact on the study, how the feedback process will be managed, and what resources are needed to support that process. Recommendations are made for actions a cohort study should consider taking when making vital decisions regarding returning findings. Any decisions need to be context-specific, arrived at transparently, communicated clearly, and in the best interests of both the participants and the study. PMID- 25126105 TI - From spatial ecology to spatial epidemiology: modeling spatial distributions of different cancer types with principal coordinates of neighbor matrices. AB - BACKGROUND: Epidemiology and ecology share many fundamental research questions. Here we describe how principal coordinates of neighbor matrices (PCNM), a method from spatial ecology, can be applied to spatial epidemiology. PCNM is based on geographical distances among sites and can be applied to any set of sites providing a good coverage of a study area. In the present study, PCNM eigenvectors corresponding to positive autocorrelation were used as explanatory variables in linear regressions to model incidences of eight most common cancer types in Finnish municipalities (n = 320). The dataset was provided by the Finnish Cancer Registry and it included altogether 615,839 cases between 1953 and 2010. RESULTS: PCNM resulted in 165 vectors with a positive eigenvalue. The first PCNM vector corresponded to the wavelength of hundreds of kilometers as it contrasted two main subareas so that municipalities located in southwestern Finland had the highest positive site scores and those located in midwestern Finland had the highest negative scores in that vector. Correspondingly, the 165(th) PCNM vector indicated variation mainly between the two small municipalities located in South Finland. The vectors explained 13 - 58% of the spatial variation in cancer incidences. The number of outliers having standardized residual > |3| was very low, one to six per model, and even lower, zero to two per model, according to Chauvenet's criterion. The spatial variation of prostate cancer was best captured (adjusted r (2) = 0.579). CONCLUSIONS: PCNM can act as a complementary method to causal modeling to achieve a better understanding of the spatial structure of both the response and explanatory variables, and to assess the spatial importance of unmeasured explanatory factors. PCNM vectors can be used as proxies for demographics and causative agents to deal with autocorrelation, multicollinearity, and confounding variables. PCNM may help to extend spatial epidemiology to areas with limited availability of registers, improve cost-effectiveness, and aid in identifying unknown causative agents, and predict future trends in disease distributions and incidences. A large advantage of using PCNM is that it can create statistically valid reflectors of real predictors for disease incidence models with only little resources and background information. PMID- 25126106 TI - Duplication of the NPHP1 gene in patients with autism spectrum disorder and normal intellectual ability: a case series. AB - Autism spectrum disorder is a neurodevelopmental disorder characterized by impairments in social interactions, reduced verbal communication abilities, stereotyped repetitive behaviors, and restricted interests. It is a complex condition caused by genetic and environmental factors; the high heritability of this disorder supports the presence of a significant genetic contribution. Many studies have suggested that copy-number variants contribute to the etiology of autism spectrum disorder. Recently, copy-number variants of the nephronophthisis 1 gene have been reported in patients with autism spectrum disorder. To the best of our knowledge, only six autism spectrum disorder cases with duplications of the nephronophthisis 1 gene have been reported. These patients exhibited intellectual dysfunction, including verbal dysfunction in one patient, below average verbal intellectual ability in one patient, and intellectual disability in four patients. In this study, we identified nephronophthisis 1 duplications in two unrelated Japanese patients with autism spectrum disorder using a high resolution single-nucleotide polymorphism array. This report is the first to describe a nephronophthisis 1 duplication in an autism spectrum disorder patient with an average verbal intelligence quotient and an average performance intelligence quotient. However, the second autism spectrum disorder patient with a nephronophthisis 1 duplication had a below-average performance intelligence quotient. Neither patient exhibited physical dysfunction, motor developmental delay, or neurological abnormalities. This study supports the clinical observation of nephronophthisis 1 duplication in autism spectrum disorder cases and might contribute to our understanding of the clinical phenotype that arises from this duplication. PMID- 25126107 TI - Privacy-preserving self-helped medical diagnosis scheme based on secure two-party computation in wireless sensor networks. AB - With the continuing growth of wireless sensor networks in pervasive medical care, people pay more and more attention to privacy in medical monitoring, diagnosis, treatment, and patient care. On one hand, we expect the public health institutions to provide us with better service. On the other hand, we would not like to leak our personal health information to them. In order to balance this contradiction, in this paper we design a privacy-preserving self-helped medical diagnosis scheme based on secure two-party computation in wireless sensor networks so that patients can privately diagnose themselves by inputting a health card into a self-helped medical diagnosis ATM to obtain a diagnostic report just like drawing money from a bank ATM without revealing patients' health information and doctors' diagnostic skill. It makes secure self-helped disease diagnosis feasible and greatly benefits patients as well as relieving the heavy pressure of public health institutions. PMID- 25126108 TI - Automatic blastomere recognition from a single embryo image. AB - The number of blastomeres of human day 3 embryos is one of the most important criteria for evaluating embryo viability. However, due to the transparency and overlap of blastomeres, it is a challenge to recognize blastomeres automatically using a single embryo image. This study proposes an approach based on least square curve fitting (LSCF) for automatic blastomere recognition from a single image. First, combining edge detection, deletion of multiple connected points, and dilation and erosion, an effective preprocessing method was designed to obtain part of blastomere edges that were singly connected. Next, an automatic recognition method for blastomeres was proposed using least square circle fitting. This algorithm was tested on 381 embryo microscopic images obtained from the eight-cell period, and the results were compared with those provided by experts. Embryos were recognized with a 0 error rate occupancy of 21.59%, and the ratio of embryos in which the false recognition number was less than or equal to 2 was 83.16%. This experiment demonstrated that our method could efficiently and rapidly recognize the number of blastomeres from a single embryo image without the need to reconstruct the three-dimensional model of the blastomeres first; this method is simple and efficient. PMID- 25126109 TI - Computational and control methods in rehabilitation medicine. PMID- 25126111 TI - Mathematical modelling of cerebral blood circulation and cerebral autoregulation: towards preventing intracranial hemorrhages in preterm newborns. AB - Impaired cerebral autoregulation leads to fluctuations in cerebral blood flow, which can be especially dangerous for immature brain of preterm newborns. In this paper, two mathematical models of cerebral autoregulation are discussed. The first one is an enhancement of a vascular model proposed by Piechnik et al. We extend this model by adding a polynomial dependence of the vascular radius on the arterial blood pressure and adjusting the polynomial coefficients to experimental data to gain the autoregulation behavior. Moreover, the inclusion of a Preisach hysteresis operator, simulating a hysteretic dependence of the cerebral blood flow on the arterial pressure, is tested. The second model couples the blood vessel system model by Piechnik et al. with an ordinary differential equation model of cerebral autoregulation by Ursino and Lodi. An optimal control setting is proposed for a simplified variant of this coupled model. The objective of the control is the maintenance of the autoregulatory function for a wider range of the arterial pressure. The control can be interpreted as the effect of a medicament changing the cerebral blood flow by, for example, dilation of blood vessels. Advanced numerical methods developed by the authors are applied for the numerical treatment of the control problem. PMID- 25126110 TI - ProBLM web server: protein and membrane placement and orientation package. AB - The 3D structures of membrane proteins are typically determined without the presence of a lipid bilayer. For the purpose of studying the role of membranes on the wild type characteristics of the corresponding protein, determining the position and orientation of transmembrane proteins within a membrane environment is highly desirable. Here we report a geometry-based approach to automatically insert a membrane protein with a known 3D structure into pregenerated lipid bilayer membranes with various dimensions and lipid compositions or into a pseudomembrane. The pseudomembrane is built using the Protein Nano-Object Integrator which generates a parallelepiped of user-specified dimensions made up of pseudoatoms. The pseudomembrane allows for modeling the desolvation effects while avoiding plausible errors associated with wrongly assigned protein-lipid contacts. The method is implemented into a web server, the ProBLM server, which is freely available to the biophysical community. The web server allows the user to upload a protein coordinate file and any missing residues or heavy atoms are regenerated. ProBLM then creates a combined protein-membrane complex from the given membrane protein and bilayer lipid membrane or pseudomembrane. The user is given an option to manually refine the model by manipulating the position and orientation of the protein with respect to the membrane. PMID- 25126112 TI - Challenges in predicting the evolutionary maintenance of a phage transgene. AB - BACKGROUND: In prior work, a phage engineered with a biofilm-degrading enzyme (dispersin B) cleared artificial, short-term biofilms more fully than the phage lacking the enzyme. An unresolved question is whether the transgene will be lost or maintained during phage growth - its loss would limit the utility of the engineering. Broadly supported evolutionary theory suggests that transgenes will be lost through a 'tragedy of the commons' mechanism unless the ecology of growth in biofilms meets specific requirements. We test that theory here. RESULTS: Functional properties of the transgenic phage were identified. Consistent with the previous study, the dispersin phage was superior to unmodified phage at clearing short term biofilms grown in broth, shown here to be an effect attributable to free enzyme. However, the dispersin phage was only marginally better than control phages on short term biofilms in minimal media and was no better than control phages in clearing long term biofilms. There was little empirical support for the tragedy of the commons framework despite a strong theoretical foundation for its supposed relevance. The framework requires that the transgene imposes an intrinsic cost, yet the transgene was intrinsically neutral or beneficial when expressed from one part of the phage genome. Expressed from a different part of the genome, the transgene did behave as if intrinsically costly, but its maintenance did not benefit from spatially structured growth per se - violating the tragedy framework. CONCLUSIONS: Overall, the transgene was beneficial under many conditions, but no insight to its maintenance was attributable to the established evolutionary framework. The failure likely resides in system details that would be used to parameterize the models. Our study cautions against naive applications of evolutionary theory to synthetic biology, even qualitatively. PMID- 25126113 TI - Minireactor-based high-throughput temperature profiling for the optimization of microbial and enzymatic processes. AB - BACKGROUND: Bioprocesses depend on a number of different operating parameters and temperature is one of the most important ones. Unfortunately, systems for rapid determination of temperature dependent reaction kinetics are rare. Obviously, there is a need for a high-throughput screening procedure of temperature dependent process behavior. Even though, well equipped micro-bioreactors are a promising approach sufficient temperature control is quite challenging and rather complex. RESULTS: In this work a unique system is presented combining an optical on-line monitoring device with a customized temperature control unit for 96 well microtiter plates. By exposing microtiter plates to specific temperature profiles, high-throughput temperature optimization for microbial and enzymatic systems in a micro-scale of 200 MUL is realized. For single well resolved temperature measurement fluorescence thermometry was used, combining the fluorescent dyes Rhodamin B and Rhodamin 110. The real time monitoring of the microbial and enzymatic reactions provides extensive data output. To evaluate this novel system the temperature optima for Escherichia coli and Kluyveromyces lactis regarding growth and recombinant protein production were determined. Furthermore, the commercial cellulase mixture Celluclast as a representative for enzymes was investigated applying a fluorescent activity assay. CONCLUSION: Microtiter plate-based high-throughput temperature profiling is a convenient tool for characterizing temperature dependent reaction processes. It allows the evaluation of numerous conditions, e.g. microorganisms, enzymes, media, and others, in a short time. The simple temperature control combined with a commercial on-line monitoring device makes it a user friendly system. PMID- 25126114 TI - A new patient with a terminal de novo 2p25.3 deletion of 1.9 Mb associated with early-onset of obesity, intellectual disabilities and hyperkinetic disorder. AB - Terminal and interstitial deletions of 2p25.3 (size < Mb), detected by array-CGH analysis, have been reported in about 18 patients sharing common clinical features represented by early-onset obesity/ overweightness associated with intellectual disabilities (ID) and behavioural troubles. This observations led to hypothesize that 2p subtelomeric deletion should be associated with syndromic obesity and MYT1L became the main candidate gene for ID and obesity since it is deleted or disrupted in all hitherto published cases. Here we described a 2p25.3 de novo terminal deletion of 1.9 Mb, of paternal origin, detected by array-CGH analysis in a girl of 4.4 years with a distinctive phenotype consisting of early onset of obesity associated with moderate ID, and hyperkinetic disorder. The deletion disrupted MYT1L and encompassed five other OMIM genes, ACP1, TMEM18, SNTG2, TPO, and PXDN. Here, we discuss the combined functional effects of additional haploinsufficient genes, that may concur with heterozygous deletion of MYT1L, in the aetiology for syndromic obesity associated with 2p25.5 subtelomeric deletion. PMID- 25126115 TI - Association between Brachial-Ankle pulse wave velocity and cardiac autonomic neuropathy in type 2 diabetes. AB - BACKGROUND: Cardiac autonomic neuropathy (CAN) is a common complication of type 2 diabetes mellitus (T2DM). Brachial-ankle pulse wave velocity (baPWV) is known to be a good surrogate marker of vascular damages. The goal of this study was to investigate the relationship between BaPWV and CAN in T2DM. METHODS: A total of 148 patients who had no apparent history of cardiovascular condition were enrolled consecutively in this study. The correlation between increased baPWV and CAN was analyzed. CAN was evaluated by five standard cardiovascular reflex tests (CARTs) according to the Ewing's protocol: 1) heart rate variation during deep breathing, 2) heart rate response to standing, 3) Valsalva maneuver, 4) postural systolic blood pressure (BP) change, 5) Sustained handgrip test. CAN was defined as the presence of at least two abnormal tests. RESULTS: The mean age of patients was 59.8 +/- 7.8 years. The mean duration of diabetes was 6.0(2.0-11.0) years. The mean baPWV was 1665.5(1482.0-1940.0) cm/sec. Subjects with CAN were older and had high BMI, baPWV compared with those without CAN. The proportion of patients with diabetic peripheral neuropathy was higher in subjects with CAN. After adjusting for other confounding risk factors, baPWV (odds ratio = 8.496, 95% CI: 1.216-59.348; P = 0.031) remained as independent risk factors for CAN. The number of abnormal CARTs increased gradually with increasing baPWV (correlation coefficient =0.255, p = 0.002). CONCLUSION: Increased baPWV was significantly correlated with CAN in patients with type 2 diabetes. PMID- 25126119 TI - Cerebral aspergilloma in a SLE patient: A case report with short literature review. AB - Aspergillosis of brain is very rare, and commonly seen in immunocompromised or immunosuppressed patient. Here, we report a cerebral aspergillosis condition in a late teen girl who is a Systemic Lupus Erythromatosis patient with steroid therapy. She developed headaches, vomitings, and convulsions. On the basis of clinical and neuroimaging, a diagnosis of cerebral tuberculoma was made, and she was put on anti-TB therapy, but she did not respond. Later, surgical partial excision biopsy confirmed the diagnosis. Her cerebral lesions responded with antifungal itraconazole therapy. The case will be presented with short literature review. Such a report in the literature is rare. PMID- 25126118 TI - Complication avoidance in transcallosal transforaminal approach to colloid cysts of the anterior third ventriclen: An analysis of 80 cases. AB - OBJECT: The objective of the present study is to analyze the complications and their avoidance in a series of 80 patients operated by transcallosal transforaminal approach to colloid cysts of the anterior third ventricle. MATERIALS AND METHODS: The surgical outcome and complications of 80 patients operated by transcallosal transforaminal approach for colloid cysts in the anterior third ventricle was analyzed. A detailed pre- and post-operative neurological assessment was done in all patients. Neurocognitive assessment of corpus callosal function was done in the last 22 cases. CT scan of the brain was done in all patients, before and after surgery. RESULTS: All patients underwent transcallosal transforaminal approach. Total excision of the lesion was achieved in 79 patients and subtotal in one. The complications encountered were postoperative seizures in six, acute hydrocephalus in four, venous cortical infarct in four, transient hemiparesis in four, transient memory impairment, especially for immediate recall in nine, mutism in one, subdural hematoma in one, meningitis in three, and tension pneumocephalus in one patient. There were two mortalities. There was no incidence of postoperative disconnection syndrome. CONCLUSION: Colloid cyst is surgically curable. With good knowledge of the regional anatomy and meticulous microsurgical techniques, there is a low mortality and minimum morbidity, when compared to the natural history of the disease. With increasing experience, most of the complications are avoidable. The limited anterior callosotomy does not result in disconnection syndromes. PMID- 25126116 TI - piRNA clusters and open chromatin structure. AB - Transposable elements (TEs) are major structural components of eukaryotic genomes; however, mobilization of TEs generally has negative effects on the host genome. To counteract this threat, host cells have evolved genetic and epigenetic mechanisms that keep TEs silenced. One such mechanism involves the Piwi-piRNA complex, which represses TEs in animal gonads either by cleaving TE transcripts in the cytoplasm or by directing specific chromatin modifications at TE loci in the nucleus. Most Piwi-interacting RNAs (piRNAs) are derived from genomic piRNA clusters. There has been remarkable progress in our understanding of the mechanisms underlying piRNA biogenesis. However, little is known about how a specific locus in the genome is converted into a piRNA-producing site. In this review, we will discuss a possible link between chromatin boundaries and piRNA cluster formation. PMID- 25126120 TI - Impact of clinico-radiological parameters on the outcome of treatment in brain tuberculosis. AB - OBJECTIVES: The Aim of this study was to evaluate the impact of clinico radiological parameters on the outcome of the treatment in brain tuberculosis. MATERIALS AND METHODS: This study was conducted in the Department of Neurosurgery and Neurology Skims Srinagar India for a period of two years from November 2009 to November 2011. A total of 61 patients presenting with brain tuberculosis admitted at skims during these two years were included in the study. Patients having clinical, laboratory and radiological findings suggestive of brain tuberculosis were included in the study. On correlating the CT characteristics tuberculomas, basal exudates and hydrocephalus with sequelae at 6,12 and 18 months - focal deficit, cognitive impairment, and diplopia. RESULTS: It was seen that basal exudates correlated with all the three neurological sequelae i.e.; with focal deficit (P = 0.001), cognitive impairment (P = 0.011), and diplopia (P = 0.021). Hydrocephalus correlated well with cognitive impairment (P = 0.031) and tuberculoma correlated with none of these clinical characteristics. CONCLUSION: We concluded that the mortality and neurologic sequelae were directly related to the clinical stage of disease at presentation. Correlating the CT characteristics we concluded that basal exudates correlated with all the three sequelae i.e.; with focal deficit, cognitive impairment, and diplopia. Hydrocephalous correlated well with cognitive impairment and tuberculoma correlated with none of these clinical characteristics. PMID- 25126121 TI - Spinal dysraphism: A challenge continued to be faced by neurosurgeons in developing countries. AB - OBJECTIVES: The incidence of spinal dysraphism has significantly decreased over the last few decades, all over the world; however, still the incidence is much higher in developing countries with poor socioeconomic status. MATERIALS AND METHODS: The present study includes all patients managed for spinal dysraphism over a period of one year (January 2011-December 2011). Details including demographics, antenatal care history, site and type of lesion, neurological examination, imaging finding, associated congenital anomalies, management offered, and outcome were recorded. RESULTS: A total of 27 children were operated for spinal dysraphism during the study period (17 males and 11 females). Median age was 120 days (age range, 1 day to 6 years). Mothers of 15 children did not seek any regular antenatal checkup and only 13 mothers received folic acid supplementation during pregnancy. Fourteen children were delivered at home and 13 were at hospital. The most common site was lumbosacral region (67.8%). Seven patients had rupture of the sac at the time of presentation, one child had local infection, and four patients had hydrocephalus (requiring shunt before surgical repair). Two patients developed hydrocephalus at follow up, needing shunt surgery. The mean hospital stay was 7 days (range, 5 days to 31 days; median, 10 days). CONCLUSION: Spinal dysraphism is still a major public health problem in developing countries. Management of patients with spinal dysraphism is complex and needs close coordination between pediatrician, neurologist, neurosurgeon, and rehabilitation experts. A large number of factors influence the outcome. PMID- 25126117 TI - Recent advances in the analysis of therapeutic proteins by capillary and microchip electrophoresis. AB - The development of therapeutic proteins and peptides is an expensive and time intensive process. Biologics, which have become a multi-billion dollar industry, are chemically complex products that require constant observation during each stage of development and production. Post-translational modifications along with chemical and physical degradation from oxidation, deamidation, and aggregation, lead to high levels of heterogeneity that affect drug quality and efficacy. The various separation modes of capillary electrophoresis (CE) are commonly utilized to perform quality control and assess protein heterogeneity. This review attempts to highlight the most recent developments and applications of CE separation techniques for the characterization of protein and peptide therapeutics by focusing on papers accepted for publication in the in the two-year period between January 2012 and December 2013. The separation principles and technological advances of CE, capillary gel electrophoresis, capillary isoelectric focusing, capillary electrochromatography and CE-mass spectrometry are discussed, along with exciting new applications of these techniques to relevant pharmaceutical issues. Also included is a small selection of papers on microchip electrophoresis to show the direction this field is moving with regards to the development of inexpensive and portable analysis systems for on-site, high-throughput analysis. PMID- 25126122 TI - Ventriculoperitoneal shunting: Laparoscopically assisted versus conventional open surgical approaches. AB - OBJECTIVES: Ventriculoperitoneal shunting (VPS) is a mainstay of hydrocephalus therapy, but carries a significant risk of device malfunctioning. This study aims to compare the outcomes of laparoscopic ventriculoperitoneal shunting versus open ventriculoperitoneal shunting (OVPS) VPS-placement and reviews our findings in the pertinent context of the literature from 1993 to 2012. MATERIALS AND METHODS: Between 2003 and 2012, a total of 232 patients underwent first time VPS placement at Beth Israel Deaconess Medical Center. Of those, 155 were laparoscopically guided and 77 were done conventionally. We analyzed independent variables (age, gender, medical history, clinical presentation, indication for surgery and surgical technique) and dependent variables (operative time, post-operative complications, length of stay in the hospital) and occurrence of shunt failure. RESULTS: Mean operative time was 43.7 min (18.0-102.0) in the laparoscopic group versus 63.0 min (30.0-151.0) in the open group, (P < 0.05). Length of stay was similar, 5 days in the laparoscopic and in the open group, (P = 0.945). The incidence of shunt failure during the entire follow-up period was not statistically different between the two groups, occurring in 14.1% in the laparoscopic group and 16.9% in the open group, (P = 0.601). Kaplan-Meier analysis demonstrated no difference in shunt survival between the two groups (P = 0.868), with functionality in 85% at 6-months and 78.5% at 1-year. CONCLUSION: According to our study, LVPS-placement results compare similarly to OVPS placement in most aspects. Since laparoscopic placement is not routinely indicated, we suggest a prospective study to assess its value as an alternate technique especially suitable in obese patients and patients with previous abdominal operations. PMID- 25126124 TI - Bed wise cost analysis of in-patient treatment of brachial plexus injury at a Level I trauma Center in India. AB - AIM: The aim was to calculate, in monetary terms, total cost incurred by a Level I trauma center in providing in-patient care to brachial plexus injury patients during their preoperative and the postoperative stay. SUBJECTS AND METHODS: All patients of brachial plexus injury admitted and discharged between January and December 2010 were included in the study. Total cost per bed was calculated under several cost heads in pre- and post-operative ward care. Intra-operative costs were excluded. RESULTS: A total of 69 patients were admitted in the year 2010. Of these 60 were operated and the rest were planned conservative management. The total cost incurred by the trauma center in providing in-patient care to patients admitted in the ward, excluding high dependency unit, came out to be Rs. 3,650.00/patient/bed/day. Of this Rs. 2,234.645, the maximum amount was incurred in providing manpower alone. The average preoperative wait was 12 days (maximum 41 days and minimum 1-day). The average postoperative stay was 2 days. Total cost incurred in the preoperative period was Rs. 2,975,125 (US$ 59392) or Rs. 43,117/patient (US$ 861). It was Rs. 386,948 (US$ 7724) in the postoperative period (Rs. 6,449 or US$ 129/patient). Nine patients were not operated and had waited from 2 to 12 days before finally being planned for observant treatment. This itself cost the hospital Rs. 226,328 (US$ 4518). CONCLUSION: By just reducing the preoperative length of stay to 1-day the cost can be brought down by 93% for brachial plexus injury patients alone and the beds can be used to admit more critical patients. PMID- 25126123 TI - EC-IC bypass for cavernous carotid aneurysms: An initial experience with twelve patients. AB - AIMS: Need for performing a bypass procedure prior to parent artery occlusion in patients with good cerebral vascular reserve is controversial. We analyze our experience of 12 giant internal carotid artery aneurysms treated with extracranial-intracranial (EC-IC) bypass and proximal artery occlusion. MATERIALS AND METHODS: Retrospective analysis of the case records of all complex carotid aneurysms operated in our institute since January 2009. RESULTS: The study included eleven cavernous carotid aneurysms and one large fusiform cervical carotid aneurysm reaching the skull base. Preoperative assessment of cerebral vascular reserve was limited to Balloon test occlusion with hypotensive challenge. Eleven patients who successfully completed a Balloon test occlusion (BTO) underwent low flow superficial temporal artery to middle cerebral artery (STA-MCA) bypass, while one patient with a failed BTO underwent a high flow bypass using a saphenous vein graft. Parent artery ligation was performed in all patients following the bypass procedure. Check angiogram revealed thrombosis of the aneurysm in all patients with a graft patency rate of 81.8%. We had one operative mortality, probably related to a leak from the anastomotic site. The only patient who had a high flow bypass developed contralateral hemispheric infarcts and remained vegetative. All the other patients had a good recovery and with a Glasgow outcome score of 5 at last follow-up. CONCLUSION: We feel that combining EC-IC bypass prior to parent vessel occlusion helps in reducing the risk of post operative ischemic complications especially in situations where a complete mandated cerebral blood flow studies are not feasible. PMID- 25126125 TI - Multicystic oligodendroglioma with calvarial destruction. AB - CONTEXT: Calvarial erosion is known to occur with some superficially located tumors. Very few case reports of calvarial erosion associated with oligodendroglioma are reported in the literature, but calvarial destruction with oligodendroglioma is very rare. AIM: To report an unusual case of multicystic frontoparietal oligodendroglioma with destruction of the calvaria and scalp involvement in the absence of prior surgery or radiation. MATERIALS AND METHODS: A 30-year-old male presented with the history of left focal seizure with secondary generalization for last three to four years along with left sided weakness for the past one month. There was history of slowly progressive decreased vision in both eyes leading to complete blindness in both eyes for the past one month. On neurological examination, patient had left hemiparesis of grade-2/5 with perception of light absent in both eyes. Fundus examination revealed bilateral optic atrophy. Magnetic resonance imaging (MRI) of the brain showed a large supratentorial heterogenous multicystic ring enhancing mass lesion involving right frontal lobe, right frontotemporal opercular region, and posteriorly abutting the central sulcus and anteriorly destroying the calvaria. Patient underwent right frontoparietal craniotomy and near total excision of tumor. Histopathological examination revealed oligodendroglioma WHO grade-2. Patient received postoperative chemoradiotherapy. RESULTS: At nine month follow up patient neurological status was same and his seizure was controlled on single AED. There was no recurrence of seizure at nine month of follow-up. CONCLUSIONS: Calvarial destruction in association with extra and intra axial neoplasm should include oligodendroglioma especially in patients with long history of symptoms, although calvarial destruction is very rare. However, the final diagnosis is established by means of histopathological examination. PMID- 25126126 TI - Intradural spinal granular cell tumor. AB - Granular cell tumor is a rare, usually benign tumor with classical histomorphology. Location of tumor varies widely within body, but spine is distinctly a rare location for this tumor. We report a rare case of granular cell tumor involving intradural extramedullary portion of lumbar region of spinal cord. Knowledge of which is important as subsequent prognosis differs from other tumor at same location. PMID- 25126127 TI - Primary Ewing's sarcoma of cervical vertebra: An uncommon presentation. AB - Ewing's sarcoma is a malignant primary bone tumor primarily seen in the long bones. Primary Ewing's sarcoma of the cranium is quite uncommon occurring in 1% of the cases. We report the occurrence of this rare lesion in a 24-year-old male presenting with progressively increasing swelling in left mastoid region mimicking a mastoid abscess which was later diagnosed on Fine needle aspiration cytology (FNAC) as a small round cell tumor as Ewing's sarcoma. Contrast enhanced computed tomography (CECT) revealed a typical moth eaten appearance in the first and second cervical vertebra. PMID- 25126128 TI - Thoracic cord compression by extramedullary hematopoiesis in thalassemia. AB - Extramedullary hematopoiesis (EMH) refers to hematopoiesis occurring outside the medulla of bone. It may be physiologic or due to pathological conditions like hematopoietic disorders. EMH can involve liver, spleen, thorax, and lymph nodes. It can involve paraspinal tissues with extension and involvement of spinal canal. In our case, the diagnosis was confirmed by the history of the patient stating underlying hematological condition and by magnetic resonance imaging (MRI) findings showing large soft tissue masses in paraspinal areas with involvement of spinal canal and leading to cord compression. PMID- 25126129 TI - Aneurysmal bone cyst: An unusual presentation of back pain. AB - Aneurysmal bone cyst (ABC) is a rare benign tumor comprising 1.4% of all primary bone tumors. It commonly involves humerus, femur, tibia, and pelvic bones. Spinal involvement is rare. The pathological appearance of the lesion is one of the blown out distension with fluid filled cavities from which it gains the name aneurysmal bone cyst. The World Health Organization has defined it as an expanding lesion with blood filled cavities separated by septa of trabecular bone or fibrous tissue containing osteoclast giant cells. We describe the case of a 20 year-old Asian male who presented with backache and pain in right leg. Radiology was suggestive of an ABC involving the posterior elements of the lumbar vertebra. Excision was performed. We discuss this unusual case, reviewing the current literature on biological behavior and management of aneurysmal bone cyst. PMID- 25126130 TI - Spheno-orbital encephalocele: A rare entity - A case report and review of literature. AB - OBJECTIVE: To report a rare case of basal encephalocele (spheno-orbital encephalocele), managed successfully in our institute. This is one of the rarest type of encephaloceles with very little literature available. In this case, sphenoid dysplasia was not associated with type 1 Neurofibromatosis. SETTINGS: Grant Medical College and Sir J.J Group of Hospitals, Byculla, Mumbai, Maharashtra, India. METHODS: A 22 year old male presented with a history of protrusion of right eye since the age of 7 years followed by progressive diminution of vision in the same eye for 5 months. MRI scan was suggestive of sphenoid dysplasia with herniation of right fronto-temporal lobe. The patient was operated upon with right frontal craniotomy with excision of encephalocele and repair of skull base. Subsequently, the patient underwent plastic surgery for facial skin remodeling. RESULTS: Patient's encephalocele reduced completely after excision and repair with good cosmetic results and no neurological deficits. There is no evidence of recurrence till recent follow-up. CONCLUSION: Basal encephaloceles are very rare. Complete excision of encephalocele with repair of the defect should be the aim to achieve cure. PMID- 25126131 TI - Epidural hematoma secondary to solitary skull metastasis from an ovarian carcinoma. AB - We report a rare case of an acute epidural hematoma (EDH) due to solitary skull metastasis in a 60-year-old patient treated earlier for ovarian carcinoma. The patient presented with head injury followed by unconsciousness and computerized tomography showed a large EDH in the right parietal region along with a contusion of left temporal-parietal lobe and subarachnoid hemorrhage in left sylvian fissure. Emergency craniotomy and evacuation of the EDH was performed and the hemorrhage was determined to be secondary to skull metastasis of ovarian carcinoma; the patient recovered and received whole brain radiation therapy. PMID- 25126132 TI - Designing and Developing Open Education Resources in Higher Education: A Molecular Biology Project. AB - Recent advances in internet technology have transformed how we gather and share information in today's world and have provided us with a platform to access educational resources and related information on the Internet. Every day, new technologies are developed that are changing the when and where we access that information. The capabilities of new technologies have allowed society to access information and learn virtually anywhere. As technical ingenuity continues to generate new technologies and paths of communication, we must look for opportunities to collaborate, share and extend our educational resources in higher education. Distributing Open Educational Resources (OER) in the form of freely licensed materials is necessary in order to laterally influence current advances in learning technologies. Online resources are being used in a variety of contexts to supplement instruction and training at higher education institutions. The aim of this Open Educational Resource project was to design and develop a blended learning instructional program to assist online users in developing familiarity with laboratory techniques prior to conducting molecular biology research in an authentic laboratory setting. This paper will look at the background of OER, describe the online materials that the Center for Cardiovascular Research (CCR) developed for open use, and discuss the outcomes and implications for use. PMID- 25126133 TI - Mindful Parenting Assessed Further: Psychometric Properties of the Dutch Version of the Interpersonal Mindfulness in Parenting Scale (IM-P). AB - Psychometric properties of the Dutch version of the Interpersonal Mindfulness in Parenting Scale (IM-P) were studied in a general population sample of mothers of adolescents (n=866) (study 1). A six-factor structure (29 items) emerged using exploratory factor analysis. A main difference from the original IM-P was that aspects of compassion and emotional awareness were separated into different factors for the self and the child, instead of combined into one factor. In a second general population sample of mothers of adolescents (n=.99), the six factor structure was confirmed using confirmatory factor analysis (study 2). The proposed 29-item version of the IM-P and its subscales were shown to have good internal consistencies, apart from the sixth factor. As expected, a high correlation was found with general mindfulness questionnaires (FFMQ and FMI). Furthermore, the IM-P correlated positively as expected with quality of life and optimism and negatively with depression and dysfunctional parenting styles. These expected indications of construct validity were found in study 2, as well as in mothers (n=112) of adolescents with type 1 diabetes mellitus (study 3) which was added to examine whether the Dutch version of the IM-P was also valid in a pediatric population. Overall, these three studies present good psychometric properties of the Dutch translation of the first measure of mindful parenting. PMID- 25126135 TI - Impact of an educational intervention on steroid prescribing and dosing effect on patient outcomes in COPD exacerbations. AB - The increasing number of patients affected by chronic obstructive pulmonary disease (COPD) and associated exacerbations has led to both rising hospital admissions and significant economic impact. Evidence-based guidelines have been formulated for COPD management recommending the use of low dose, oral corticosteroid therapy in the treatment of exacerbations. However, fewer than 50% of physicians' prescribing practices appropriately reflect the published clinical guidelines on the use of systemic corticosteroids in these patients. OBJECTIVE: The purpose of this study was to evaluate the impact of a pharmacist-led educational intervention on prescribing practices and patient outcomes when using systemic corticosteroids in patients with COPD exacerbations. METHODS: This retrospective case-control study included patients admitted to an inpatient family medicine service with a COPD exacerbation who received systemic corticosteroids. Two pharmacist-led educational interventions were delivered to prescribers to review current guidelines for managing COPD exacerbations with systemic corticosteroids. Patients were retrospectively identified over a three month span prior to and following the educational intervention. Data was collected via chart review to evaluate prescribing practices prior to and following the educational sessions. In addition, data was collected to evaluate the effects of an educational intervention on length of stay, adverse events, and cost of treatment. RESULTS: A total of 23 pre-intervention patients and 18 post intervention patients met inclusion criteria. After pharmacist-led interventions, guidelines were not more likely to be adhered to by prescribers when compared to guideline adherence in the pre-intervention patients. Because no statistically significant change in guideline adherence was observed, there was no impact on secondary outcomes. CONCLUSION: Pharmacist-led didactic educational interventions and guideline dissemination do not improve guideline adherence and prescribing practices with respect to systemic corticosteroids in COPD exacerbations. PMID- 25126134 TI - Medication adherence: a review of pharmacy education, research, practice and policy in Finland. AB - AIMS: To describe pharmacy education, research, practice and policy related to medication adherence in Finland since the year 2000. METHODS: The three universities that provide pharmacy education (Abo Akademi, University of Eastern Finland, and University of Helsinki) completed a structured pro-forma questionnaire regarding education related to medication adherence. A MEDLINE and EMBASE literature search was performed to identify English language peer-reviewed research that reported medication compliance, adherence or persistence. The Ministry of Social Affairs and Health was invited to nominate policies and documents related to medication adherence. A narrative review of medication counselling practices and professional service delivery through Finnish community pharmacies was undertaken. RESULTS: Medication adherence was a theme integrated into obligatory and elective courses for bachelors and masters degree students. The literature search identified 33 English language peer-reviewed research articles reporting medication compliance, adherence or persistence published since the year 2000. Policy documents of the Ministry of Social Affairs and Health recognise that poor medication adherence may lead to suboptimal treatment outcomes, and encourage patient participation in treatment decision making. Adherence practice in Finnish pharmacies has been strongly linked to the development of medication counselling services. CONCLUSIONS: Adherence research and education has focused on understanding and addressing the contextual factors that contribute to medication nonadherence. Adherence practice in community pharmacies has tended to focus on medication counselling and programs specific to particular disease states. Medication adherence is a topic that is integrated into courses for bachelor's and master's level pharmacy students in Finland. PMID- 25126136 TI - Physicians' generic drug prescribing behavior in district hospitals: a case of Phitsanulok, Thailand. AB - Generic prescribing is a sound approach to contain health care costs. However, little is known about physicians' prescribing patterns in the Thai context. OBJECTIVE: To explore physicians' generic prescription patterns in district hospitals. METHODS: Data was collected from three of the eight district hospitals between January and December 2008 (final response rate 37.5%). All participating hospitals were between 30 and 60-bed capacity. The researchers reviewed 10% of total outpatient prescriptions in each hospital. RESULTS: A total of 14,500 prescriptions were evaluated. The majority of patients were under universal health coverage (4,367; 30.1%), followed by senior citizens' health insurance (2,734; 18.9%), and civil servant medical benefit schemes (2,419; 16.7%). Ten thousand six hundred and seventy-one prescriptions (73.6% of total prescriptions) had at least one medication. Among these, each prescription contained 2.85 (SD=1.69) items. The majority of prescriptions (7,886; 73.9%) were prescribed by generic name only. Drugs prescribed by brand names varied in their pharmacological actions. They represented both innovator and branded-generic items. Interestingly, a large number of them were fixed-dose combination drugs. All brand name prescriptions were off patented. In addition, none of the brand name drugs prescribed were categorized as narrow therapeutic range or any other drug that had been reported to have had problems with generic substitution. CONCLUSION: The majority of prescriptions in this sample were written by generic names. There is room for improvement in brand name prescribing patterns. PMID- 25126137 TI - Impact of emergency contraception status on unintended pregnancy: observational data from a women's health practice. AB - OBJECTIVE: This study aimed to determine if nonprescription emergency contraception (EC) availability impacted self-reported unintended pregnancy rates and to assess women's knowledge and awareness of EC prior to and after nonprescription availability. METHODS: A survey regarding contraception use and knowledge was verbally administered to a cross-sectional, convenience sample of 272 pregnant women receiving prenatal care at a large urban community women's clinic between August 2003 and October 2008. Statistical analyses determined the differences between two groups (before [BA] and after, [AA] non-prescription EC availability in the U.S. drug market) in terms of self-reported unintended pregnancy rates, knowledge and awareness of EC. RESULTS: The AA group reported higher incidence of unintended pregnancy when compared to the BA group (90.7% vs. 72.7%, P = 0.0172). The majority of both groups reported that they were not using any contraception at the time of conception (BA-84.4%; AA-83.3%). There was no significant difference in the participants' awareness of EC between the two groups (BA-46.8% vs. AA-43.0%) nor was there a significant difference between the two groups in the self-reported willingness to use EC in the future (BA-53.1% vs. AA-63.4%). However, among participants who were unaware of EC, 61% reported they would consider using it in the future after receiving brief EC counseling from a pharmacist or student pharmacist. Neither age nor pregnancy intention was associated with self-reported EC awareness but there was an association with income (P = 0.0410) and education (P = 0.0021). CONCLUSION: The change from prescription-only to non-prescription status of EC in the U.S. drug market did not impact the unintended pregnancy rate in this patient population. Lack of knowledge and awareness is still a major barrier to widespread EC use. PMID- 25126138 TI - Pattern and quality of scientific communications on drug safety produced by a regional pharmacovigilance center in Nepal. AB - Analyzing the pattern and quality of scientific communications on pharmacovigilance can help the regional centers in Nepal and other developing countries to develop approaches for communicating effectively medicine safety issues. This kind of research is lacking in developing countries. OBJECTIVES: To analyze the pattern and quality of scientific communications on drug safety produced by the regional pharmacovigilance center at western Nepal. METHODOLOGY: Various conference abstracts and journal publications produced by the center during its initial four years of establishment (14th September 2004 till 13th September 2008) were identified. These communications were categorized in to case reports, review articles, conference presentations, short communications, newsletter and bulletin articles, original research and case series. In addition, the quality of the case reports were evaluated as per International Society of Pharmacovigilance/International Society of Pharmacoepidemiology (ISoP/ISPE) guidelines on the requirements for submitting case reports on adverse event reports in biomedical journals. RESULTS: During the study period, 53 scientific communications were produced by the staff of the regional pharmacovigilance center in relation with drug safety. Among these, 18 (34%) were related to case reports and letters. The median (interquartile range) age of the patients described in the case reports was 46.5 (21.7-51.2) years. Among the total 18 ADRs, four were fixed drug eruptions, followed by contact dermatitis (n=2). Majority of the published case reports were related to skin (n=13; 72.2%). Antimicrobials were responsible for 27.8% (n=5) of the case reports. Among the 18 case reports published by the pharmacovigilance center, a majority followed the ISoP/ISPE guidelines. Few parameters like physical examination of the patient experiencing ADR, patient disposition, dosage and administration of the suspected drugs, and drug-reaction interface were missing in few of the cases. CONCLUSION: A high percentage of the scientific communications were 'case reports'. A high proportion of the case reports produced by the center were of international standards. There were lacunae in 'patient disposition' in few of the reports. PMID- 25126139 TI - Patients' blood pressure knowledge, perceptions and monitoring practices in community pharmacies. AB - Hypertension is a modifiable risk factor for cardiovascular disease. Despite this, patients often cannot or inaccurately estimate their risk factors. OBJECTIVES: IN ORDER TO IMPROVE PHARMACIST INTERVENTIONS, WE SOUGHT TO: 1) find out patients' knowledge about blood pressure (BP) and their self-monitoring behaviors and 2) identify the relationships between these two elements. Specifically, if evaluation of BP control were related to knowledge of one's BP level and self-monitoring habits, and if knowledge of one's target and BP level varied with monitoring habits. METHODS: Final year pharmacy students were trained and interviewed patients in community pharmacies as a required exercise in their pharmacy clerkship. Each student recruited a convenience sample of 5-10 patients who were on hypertension medication, and surveyed them regarding their BP targets, recent BP levels as well as monthly and home BP monitoring practices. RESULTS: One third of the 449 patients interviewed were able to report a blood pressure target with 26% reporting a JNC 7 recognized target. Three quarters of patients who reported a blood pressure target were able to report a blood pressure level, with 12% being at their self-reported target. Roughly two thirds of patients perceived their BP to be "about right", and slightly less than a third thought it to be "high". Sixty percent of patients monitor their BP monthly, but less than 50% of patients practice home BP monitoring. CONCLUSIONS: This study along with others before it point to the knowledge and self-management gaps in patients with chronic conditions. Furthermore, pharmacy students were able to use a brief intervention to screen patients during routine care. Pharmacists can help improve patient understanding and promote increased self management through regular BP monitoring. PMID- 25126140 TI - Influence of population and general practice characteristics on prescribing of minor tranquilisers in primary care. AB - Prevalence of generalised anxiety disorders is widespread in Great Britain. Previous small-scale research has shown variations in minor tranquiliser prescribing, identifying several potential predictors of prescribing volume. OBJECTIVE: This study aimed to investigate the relationship between general practice minor tranquiliser prescribing rates and practice population and general practice characteristics for all general practices in England. METHODS: Multiple regression analysis of minor tranquiliser prescribing volumes during 2004/2005 for 8,291 English general practices with general practice and population variables obtained from the General Medical Services (GMS) statistics, Quality and Outcomes Framework (QOF), 2001 Census and 2004 Index of Multiple Deprivation (IMD). RESULTS: The highest rates of minor tranquiliser prescribing were in areas with the greatest local deprivation while general practices situated in areas with larger proportions of residents of black ethnic origin had lower rates of prescribing. Other predictors of increased prescribing were general practices with older general practitioners and general practices with older registered practice populations. CONCLUSION: Our findings show that there is wide variation of minor tranquilisers prescribing across England which has implications regarding access to treatment and inequity of service provision. Future research should determine the barriers to equitable prescribing amongst general practices serving larger populations of black ethnic origin. PMID- 25126141 TI - Pattern of adverse drug reactions reported by the community pharmacists in Nepal. AB - The pharmacovigilance program in Nepal is less than a decade old, and is hospital centered. This study highlights the findings of a community based pharmacovigilance program involving the community pharmacists. OBJECTIVES: To collect the demographic details of the patients experiencing adverse drug reactions (ADR) reported by the community pharmacists; to identify the common drugs causing the ADRs, the common types of ADRs; and to carry out the causality, severity and preventability assessments of the reported ADRs. METHODS: The baseline Knowledge-Attitude-Practices (KAP) of 116 community pharmacists from Pokhara valley towards drug safety was evaluated using a validated (Cronbach alpha=0.61) KAP questionnaire having 20 questions [(knowledge 11, attitude 5 and practice 4) maximum possible score 40]. Thirty community pharmacists with high scores were selected for three training sessions, each session lasting for one to two hours, covering the basic knowledge required for the community pharmacists for ADR reporting. Pharmacist from the regional pharmacovigilance center visited the trained community pharmacists every alternate day and collected the filled ADR reporting forms. RESULTS: Altogether 71 ADRs, from 71 patients (37 males) were reported. Antibiotics/ antibacterials caused 42% (n=37) of the total ADRs followed by non steroidal anti-inflammatory drugs [25% (n=22)]. Ibuprofen/paracetamol combination accounted for ten ADRs. The most common type of ADR was itching [17.2 % (n=20), followed by generalized edema [8.6 % (n=10)]. In order to manage the ADRs, the patients needed medical treatment in 69% (n=49) of the cases. Over two third (69%) of the ADRs had a 'possible' association with the suspected drugs and a high percentage (70.4%) were of 'mild (level 2)' type. Nearly two third [64.7 % (n=46)] of the ADRs were 'definitely preventable'. CONCLUSION: The common class of drugs known to cause ADRs was antibacterial/ antibiotics. Ibuprofen/ Paracetamol combination use of the drug was responsible for more number of ADRs and the most common ADRs were related to dermatological system. Strengthening this program might improve safe use of medicines in the community. PMID- 25126142 TI - Adherence policy, education and practice - an international perspective. AB - Nonadherence to chronic therapy has become a large burden on the healthcare system of many countries. Community pharmacists are well positioned to address nonadherence as part of their overall patient care activities, and contribute to patients' quality use of medicines. Between 2008 and 2010, a series of narrative, peer-reviewed articles were published in Pharmacy Practice which focused on community pharmacists' activities in medication adherence, specifically in the areas of the education they receive, their practice, the research conducted and national or local policies. This editorial aims to summarise the key findings presented in the series, and highlight the pertinent issues and gaps in the literature. There is a need to implement global and long-term objectives focussing on enhancing the quality of education and competencies of community pharmacists and the research conducted in medication adherence, to develop guidelines for pharmacists and enhance the uptake of adherence promoting services in routine care. PMID- 25126143 TI - Granulocyte colony-stimulating factor use in a large British hospital: comparison with published experience. AB - Granulocyte colony-stimulating factors (G-CSF) are high-cost agents recommended as prophylaxis of febrile neutropenia or as adjunctive treatment of severe neutropenic sepsis. Their use in high-risk situations such as acute myeloid leukaemia, acute lymphocytic leukaemia, myelodysplastic syndrome and stem cell transplantation is also indicated. OBJECTIVE: This audit assessed the use of G CSF within the Oncology and Haematology Service Delivery Unit at Guy's and St. Thomas' hospital (London, United Kingdom). METHODS: Patients who received G-CSF in April-May 2008 were identified retrospectively from the pharmacy labelling system, and chemotherapy front sheets, clinic letters and transplantation protocols were reviewed. Patients on lenograstim, in clinical trials or under non approved chemotherapy protocols were excluded. RESULTS: A total of 104 G-CSF treatments were assessed. The most commonly treated malignancy was breast cancer (41.3%), with docetaxel 100 mg/m (2) (34.6%) being the most frequent chemotherapy regimen. The chemotherapy intent was curative in 66.3 % of cases. Pegfilgrastim was used in 73.1 % of cases and primary prophylaxis was the most common indication (54.8%). Stem cell transplantation was the first indication to meet the audit criterion (93.3%), followed by primary prophylaxis (89.5%). There was a considerable nonadherence for secondary prophylaxis (6.7%). CONCLUSION: The overall level of compliance with the audit criteria was 72.1%. The results for primary and secondary prophylaxis would have been different if FEC100 (fluorouracil, epirubicin, cyclophosphamide) and docetaxel 100 mg/m (2) had been considered a single chemotherapy regimen. Also, the lack of access to medical notes may have affected the reliability of the results for 'therapeutic' use. PMID- 25126144 TI - Knowledge and use of folic acid among college women: a pilot health promotion program led by pharmacy students and faculty. AB - As pharmacists and pharmacy students are increasingly called upon to assume roles in public health activities, it is important to recognize unique opportunities to educate community members on health, wellness, and disease prevention. OBJECTIVE: To evaluate the impact of a pilot health promotion program on college women's knowledge regarding folic acid and prevention of neural tube defects (NTD) and frequency of multivitamin use. METHODS: A health promotion program was developed by a pharmacy student and two pharmacy faculty members that included an oral presentation and reminder messages. A multiple-choice test assessing knowledge of folic acid and NTD and frequency of multivitamin use was given to participants before and immediately after the presentation. Participants then received a reminder message regarding folic acid once a week for three weeks. Knowledge and multivitamin use were reassessed four weeks post-intervention. RESULTS: Thirty two college women voluntarily attended the oral presentation. Twenty-five women (78.2%) completed the four-week post-test. Compared to the pre-test, there were statistically significant increases in average test score (p<0.0001) and correct responses to questions regarding folic acid and NTD (p<0.05 for each question). Participants reported a statistically significant increase in regular (>=4 times/week) multivitamin use (p=0.023). CONCLUSION: Participants in the pilot health promotion program demonstrated a statistically significant increase in knowledge about folic acid and frequency of multivitamin use. A similarly-modeled health promotion program may be an effective way of increasing folic acid and NTD knowledge and changing behaviors of multivitamin use in college women. PMID- 25126145 TI - Medication storage and self-medication behaviour amongst female students in Malaysia. AB - OBJECTIVES: The aims of this study are to determine the prevalence, attitudes and behaviours of medication storage and self-medication amongst female students at Universiti Sains Malaysia (USM). METHODS: A cross-sectional survey was conducted and cluster random sampling technique was used for respondent selection. A pre piloted questionnaire was administered to female respondents so as to collect the data. Data was analyzed using SPSS version 12 and analysis was conducted using descriptive analysis procedures. RESULTS: Of the 481 participants (mean age; SD was 22.1; 3.3), 93.1% (n=448) students stated that they stored medicine in their rooms, while 70.7% (n=340) stated that they stopped taking a prescribed medicine without consulting a doctor. The prevalence of self-medication was 80.9% (n=389). The most common reasons for self-medication were related to their knowledge of their ailment and its treatment (58.0%), 14.4% thought it saved time and 8.5% mentioned that medication given by provider was not effective. The most common symptoms were otorhinolaryngology problems (22.5%), followed by respiratory disease (19.6%), Gastro Intestinal Tract (GIT) disease (18.1%) and headache/fever (16.8%). Commonly used medicines were analgesics & antipyretics (30.2%), ear, nose & throat drugs (10.8%), vitamins & minerals (10.8%), GIT drugs (8.5%), anti infections (7.3%) and herbal medicines (3.5%). Prevalence of medicine storage and self-medication practice is high among educated female students in USM. CONCLUSIONS: There is a need to educate the students to ensure safe practice by increasing their awareness. Strict policies need to be implemented on the unrestricted availability of medicines so as to prevent the wastage of medicines. PMID- 25126146 TI - Self medication among hospitalized patients in selected secondary health facilities in South Western Nigeria. AB - Practice of self-medication has not been evaluated in hospitalized patients especially in Nigerian hospitals. OBJECTIVES: To evaluate the practice of self medication among hospitalized patients with an aim to unearth some of the reasons for, and perceptions of benefits of this type of behaviour in secondary health care facilities. METHODS: This study was carried out among 197 in-patients admitted in three secondary health facilities in southwestern Nigeria using structured questionnaire. Effects of variables such as age, gender and marital status on the practice of self medication were also evaluated using the Fisher's Exact test at p<0.05 as level of significance. RESULTS: Response rate of the study was 93.8% with 174 respondents (88.3%) perceived that the medications prescribed for them were efficacious. Almost 38% of the respondents were self medicating, with herbal medicines (29.2%) and western medicines (37%) partly due to side effects of the prescribed medicines. Thirty one (15.7%) respondents obtained medicines for self medication through relatives and friends. Prescription medicines used for self medication constituted 7.5%. Major reasons given for self medication included habit, availability and necessity. Ninety respondents (35.7%) had been informed by health care personnel about possible side effects of the medications. Ninety six respondents (48.7%) experienced side effects with the prescribed medications and was a major reason for self medication. Seventy six respondents (79.2%) who had side effects or other secondary symptoms informed healthcare personnel in the hospital while 16 (16.7%) informed relatives and friends. There was statistically significant association between age and the action taken on whom was informed (p=0.001). CONCLUSIONS: There is need for extra vigilance from health personnel directly responsible for care of hospitalized patients to look for incidences of self-medication and patient education on the negative aspects of administering undisclosed medicines to their health care givers especially while they are hospitalized. PMID- 25126147 TI - New Zealand parent's perceptions of the use and safety of over the counter liquid analgesics. AB - OBJECTIVE: The objective of this study was to investigate the knowledge of parents and caregivers with respect to the purchase, use and storage of liquid analgesics purchased over the counter (OTC) from pharmacies. This would enable specific strategies to be identified to increase awareness of the potential risks of these products. METHODS: Questionnaires were developed and used a combination of Likert Scales, open ended questions and yes/no answers. Randomly chosen New Zealand pharmacies (463) were asked to approach a person purchasing liquid analgesics and ask them to complete the questionnaire. Of the 105 pharmacies that participated, 96 completed parent/caregiver questionnaires were returned. RESULTS: When choosing a product there was a statistically significant difference between the most important factors 'safety' and 'active ingredient' and the least important factors 'cost' and if the parent/caregiver 'used it before'. All parents/caregivers claim to have received verbal information from pharmacy staff, with 40% stating that they 'always' receive information. The majority of parents/caregivers store medicines in a high place (n=61), in a cupboard (n=56) or a combination of these. Over half (52%) of the parents/caregivers thought that children could 'never' open child resistant closures. CONCLUSION: Whilst parents and caregivers choose products based on perceived safety, there is an over estimation in the perception of the protection that a child resistant closure actually offers. The general public needs to continually be vigilant in the use, storage and administration when using medication in the vicinity of children. PMID- 25126148 TI - Increasing use of artemisinin-based combination therapy for treatment of malaria infection in Nigerian hospitals. AB - OBJECTIVES: This study aimed at describing the pattern of outpatient antimalarial drug prescribing in a secondary and a tertiary hospital, and to assess adherence to the National Antimalarial Treatment Guideline (ATG). METHODS: An audit of antimalarial prescription files from the two health facilities for a period of six months in 2008 was conducted. Semi structured questionnaires were used to collect information from the doctors and pharmacists on their awareness and knowledge of the National Antimalarial Treatment Guideline. RESULTS: Artemisinin based combination therapies (ACTs) were the most prescribed antimalarials. Overall, 81.4% of the total prescriptions contained ACTs, out of which 56.8% were artemetherlumefantrine. However, adherence to the drugs indicated by national guideline within the DU90% was 38.5% for the tertiary and 66.7 % for the secondary hospital. The standard practice of prescribing with generic name was still not adhered to as evidenced in the understudied hospitals. The percentage of health care providers that were aware of the ATG was 88.2% for doctors and 85.1% for pharmacists. However, 13.3% and 52.2% of doctors and pharmacists respectively could not properly list the drugs specified in the guideline. Amodiaquine was the most commonly preferred option for managing children aged 0 - 3 months with malaria infection against the indicated oral quinine. CONCLUSION: This study showed an increased use of artemisinin-based combination therapy for the treatment of uncomplicated malaria compared previous reports in Nigeria. This study also highlights the need for periodic in-service quality assurance among health professionals with monitoring of adherence to and assessment of knowledge of clinical guidelines to ensure the practice of evidence based medicine. PMID- 25126149 TI - Evaluation of a pharmacist-managed diabetes medication therapy adherence clinic. AB - Patient adherence to prescribed medication regimens is important in diabetes care to prevent or delay microvascular and macrovascular complications such as retinopathy, nephropathy and myocardial infarction. In Penang Hospital, Malaysia, pharmacists collaborate with physicians in diabetes care through a pharmacist managed Diabetes Medication Therapy Adherence Clinic (DMTAC) in the Endocrine Clinic, in operation since 2006. OBJECTIVE: To evaluate the effectiveness of the pharmacist-managed DMTAC program in improving glycaemic control, lipid parameters and patients' medication adherence. METHOD: A retrospective study among patients enrolled in the DMTAC program was conducted between September 2007 and December 2008. Data was included from patients with a glycosylated haemoglobin (HbA1c) >8% and who had completed eight visits with the pharmacists. Medical records and DMTAC forms that provided patients' demographics, medication regimens, adherence and laboratory parameters as well as pharmacists' interventions were reviewed. HbA1c, fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL), triglycerides (TG) and high-density lipoprotein cholesterol (HDL) were evaluated. Documented data of patients' adherence to medication regimen [Modified Morisky Medication Adherence Score (MMMAS); high adherence if score >8, medium adherence if score 6 to <8 and low adherence if score <6] was also evaluated. RESULTS: A total of 43 patients (53.5% females; 46.5% Malays, 44.2% Chinese and 9.3% Indians) were included in the analysis. A mean reduction in HbA1c of 1.73% (p<0.001), mean reduction in FBG of 2.65mmol/l (p=0.01) and mean reduction in LDL cholesterol of 0.38mmol/l (p=0.007) were achieved. The difference in TG and HDL cholesterol were not significant. Patients' adherence to medication regimens improved significantly with an increase in the mean MMMAS score from 7.00 to 10.84 (p<0.001) after completion of the DMTAC program. CONCLUSION: The pharmacist managed DMTAC program resulted in significant improvements in HbA1c, glucose and LDL cholesterol levels as well as medication adherence in patients with diabetes. PMID- 25126150 TI - Educational innovations: Categories of bulletin board postings designed to increase awareness of contemporary pharmaceutical policy issues. AB - OBJECTIVE: The goal of this project was to categorize and classify bulletin board postings pertaining to pharmaceutical policy from both the professional and lay press. METHODS: Bulletin board postings were used to supplement in-class discussion to keep students, faculty and staff up-to-date on emerging trends. A bulletin board located in the main classroom area of the College of Pharmacy Building where students would pass by on the way to class and congregate during break periods was used to display articles from various sources concerning topics related to pharmaceutical policy. Information is presented about the primary subject matters addressed in the articles, the types of publications from which they were drawn, and the top ten sources of articles displayed. RESULTS: This project showed that coverage of issues related to pharmacists is predominantly seen in newspapers and most pertinent issues are business related. CONCLUSIONS: It can be seen from this analysis that the issues facing pharmacists are varied. The pharmaceutical policy field is transforming and many of these changes are very relevant to the general population. This is seen from the coverage of all of these issues in the lay press. PMID- 25126151 TI - Pancreatic Lipomas - Prevalence in Patients Undergoing Abdominal CT. AB - BACKGROUND: Pancreatic lipomas are reported to be rare but their prevalence is unknown. This study examined the prevalence of pancreatic lipomas in a sample of patients undergoing abdominal computed tomography. MATERIAL/METHODS: Retrospective review of 100 abdominal computed tomographic scans. RESULTS: In 6 patients small pancreatic lipomas were found. There was no predominance in location or gender. The lipomas measured between 4 and 12 mm. All lipomas were incidental findings unrelated to patients' symptoms. CONCLUSIONS: Pancreatic lipomas seem to be quite a common finding and can be found in 6% of patients undergoing abdominal CT. Radiologists should be aware of this finding to establish proper differential diagnosis. PMID- 25126152 TI - Uncovering health literacy: Developing a remotely administered questionnaire for determining health literacy levels in health disparate populations. AB - INTRODUCTION: Low health literacy contributes to health disparities. We sought to develop and evaluate a remotely administered tool to measure health literacy in health disparate populations. The basic research design involved asking the remotely administered questions in conjunction with an existing and valid measure of health literacy, the S-TOFHLA, to a non-representative convenience sample of individuals drawn from lower income communities. The measures of the remotely administered questions were then correlated with the results of the S-TOFHLA to determine if there was a connection between the two measures. We found a statistically significant correlation between a single question in the remotely administered survey and the validated S-TOFHLA measure. This research supports previous work that points to the importance of just a single remotely administered question in terms of correspondence with the S-TOFHLA. OBJECTIVE: Develop a questionnaire that can be remotely administered to check for Health Literacy. METHODS: Correlation analysis is conducted between various questions and S-TOFHLA scores to determine criterion validity. RESULTS: A single question, "How confident are you in filling out medical forms by yourself?" outperforms other measures in correlating with the S-TOFHLA scores. CONCLUSIONS: Further assessment of the confidence question both in isolation and in conjunction with other literacy identifiers should be conducted. Also, this question should be tested against other measures of health literacy beyond the S-TOFHLA. PMID- 25126153 TI - A Fabry-Perot Interferometry Based MRI-Compatible Miniature Uniaxial Force Sensor for Percutaneous Needle Placement. AB - Robot-assisted surgical procedures, taking advantage of the high soft tissue contrast and real-time imaging of magnetic resonance imaging (MRI), are developing rapidly. However, it is crucial to maintain tactile force feedback in MRI-guided needle-based procedures. This paper presents a Fabry-Perot interference (FPI) based system of an MRI-compatible fiber optic sensor which has been integrated into a piezoelectrically actuated robot for prostate cancer biopsy and brachytherapy in 3T MRI scanner. The opto-electronic sensing system design was minimized to fit inside an MRI-compatible robot controller enclosure. A flexure mechanism was designed that integrates the FPI sensor fiber for measuring needle insertion force, and finite element analysis was performed for optimizing the correct force-deformation relationship. The compact, low-cost FPI sensing system was integrated into the robot and calibration was conducted. The root mean square (RMS) error of the calibration among the range of 0-10 Newton was 0.318 Newton comparing to the theoretical model which has been proven sufficient for robot control and teleoperation. PMID- 25126154 TI - Steering Fluorescence Emission with Metal-Dielectric-Metal Structures of Au, Ag and Al. AB - Directional control over fluorescence emission is important for improving the sensitivity of fluorescence based techniques. In recent years, plasmonic and photonic structures have shown great promise in shaping the spectral and spatial distribution of fluorescence, which otherwise is typically isotropic in nature and independent of the observation direction. In this work we have explored the potential of metal-dielectric-metal (MDM) structures composed of Au, Ag or Al in steering the fluorescence emission from various probes emitting in the NIR, Visible or UV/blue region. We show that depending on the optical properties of the metal and the thickness of the dielectric layer, the emission from randomly oriented fluorophores embedded within the MDM substrate is transformed into beaming emission normal to the substrate. Agreement of the observed angular emission patterns with reflectivity calculations reveals that the directional emission is due to the coupling of the fluorescence with the electromagnetic modes supported by the MDM structure. PMID- 25126155 TI - Sensing Reversible Protein-Ligand Interactions with Single-Walled Carbon Nanotube Field-Effect Transistors. AB - We report on the reversible detection of CaptAvidin, a tyrosine modified avidin, with single-walled carbon nanotube (SWNT) field-effect transistors (FETs) noncovalently functionalized with biotin moieties using 1-pyrenebutyric acid as a linker. Binding affinities at different pH values were quantified, and the sensor's response at various ionic strengths was analyzed. Furthermore, protein "fingerprints" of NeutrAvidin and streptavidin were obtained by monitoring their adsorption at several pH values. Moreover, gold nanoparticle decorated SWNT FETs were functionalized with biotin using 1-pyrenebutyric acid as a linker for the CNT surface and (+/-)-alpha-lipoic acid linkers for the gold surface, and reversible CaptAvidin binding is shown, paving the way for potential dual mode measurements with the addition of surface enhanced Raman spectroscopy (SERS). PMID- 25126156 TI - Effects of van der Waals Interactions in the Adsorption of Isooctane and Ethanol on Fe(100) Surfaces. AB - van der Waals (vdW) forces play a fundamental role in the structure and behavior of diverse systems. Because of development of functionals that include nonlocal correlation, it is possible to study the effects of vdW interactions in systems of industrial and tribological interest. Here we simulated within the framework of density functional theory (DFT) the adsorption of isooctane (2,2,4 trimethylpentane) and ethanol on an Fe(100) surface, employing various exchange correlation functionals to take vdW forces into account. In particular, this paper discusses the effect of vdW forces on the magnitude of adsorption energies, equilibrium geometries, and their role in the binding mechanism. According to our calculations, vdW interactions increase the adsorption energies and reduce the equilibrium distances. Nevertheless, they do not influence the spatial configuration of the adsorbed molecules. Their effect on the electronic density is a nonisotropic, delocalized accumulation of charge between the molecule and the slab. In conclusion, vdW forces are essential for the adsorption of isooctane and ethanol on a bcc Fe(100) surface. PMID- 25126157 TI - Stereotactic Ablative Radiotherapy (SABR): Impact on the Immune System and Potential for Future Therapeutic Modulation. AB - Stereotactic ablative radiotherapy (SABR) has been demonstrated to provide excellent local control in several malignancies. Recent reports have suggested that this ablative dose may impact disease outside of the radiated area. Furthermore, these studies have implicated immune modulation as the primary mechanism of disease response outside the irradiated area. More specifically, T cell stimulation and tumor necrosis factor-alpha modulation following high dose irradiation have been suggested as the responsible components of this phenomenon. In addition, the "abscopal effect" may play a role in disease response outside of the radiated area. We review the current literature regarding the effects of ablative radiation therapy, the potential for immune modulation from it, and the mechanisms of the distant effects it elicits. PMID- 25126158 TI - Signal transductions and nonalcoholic fatty liver: a mini-review. AB - Nonalcoholic fatty liver disease (NAFLD) is a common liver disease, and the incidence increases year by year. The pathogenesis of NAFLD is correlated with insulin resistant (IR), and oxidative stress which induces varied inflammatory cytokines (TNF-alpha, IL-1, IL-6, etc). Different signal transductions such as MAPK, NF-kappaB, AMPK, JAK2/STAT3, PPAR, PI3K/Akt, TLR were activated by the pathogenic factors to regulate correlative reactions. Thus, in-depth study of the signal transductions will probably provide new suitable solutions for the prevention and therapy of NAFLD. PMID- 25126159 TI - Oropharyngeal airway changes after rapid maxillary expansion: the state of the art. AB - The aim of this article is to elucidate the state of the art about how rapid maxillary expansion (RME) produces changes in the oropharyngeal airways in terms of CBCT (Cone Beam Computed Tomography) data during the growth period, according to the available literature. Electronic search was done from January 2009 to April 2014 on PubMed and Scopus databases; in addition manual search was conducted as well. According to keywords, seven papers were eligible for our purpose, but definitely five papers were selected in agreement with the inclusion/exclusion criteria. The current literature suggests that the potential relationship between RME and oropharyngeal airway changes is still unclear. In fact, although the pharyngeal airway changes after the rapid palatal expansion are evident clinically, current orthodontic literature does not provide conclusive evidence about the nature of this relationship. PMID- 25126160 TI - MicroRNA-132 silencing decreases the spontaneous recurrent seizures. AB - OBJECTIVE: This study aimed to investigate the role of microRNA-132 in the epileptogenesis. METHODS: Antagomir-132 (Ant-132) was used to silence the expression of miR-132 and non-targeting scrambled sequence (Scr) as a control. Rats were randomly divided into ant-132 group and Scr group in which rats were pretreated with An-132 and Scr, respectively, and then induced temporal lobe epilepsy (TLE) by Li-Pilo. Behavioral observation was done, and results showed the changes in spontaneous recurrent seizures in the chronic phase between two groups. Bax and Bcl-2 were detected aiming to evaluate the neuronal apoptosis. NPY staining was done to investigate the mossy fiber sprouting (MFS). Golgi staining was used to assess the changes in the dendritic morphology. RESULTS: Our study showed that ant-132 induced miR-132 silencing in rats could increase the on set epilepsy threshold and suppress the numbers of spontaneous recurrent seizures. The number of apoptotic neurons and MFS reduced after miR-132 silencing. In addition, the dendrites of neurons were highly suppressed in the CA3 region of the hippocampus. CONCLUSIONS: miR-132 silencing suppresses the spontaneous seizures. The better outcome may result from the neuroprotective effect and the inhibition of MFs-CA3 pathway following miR-132 silencing. Thus, miR-132 may serve as a potential target for the development of anti-epileptic drugs. PMID- 25126161 TI - TREM-1 as a potential therapeutic target in neonatal sepsis. AB - OBJECTIVE: Bacterial sepsis in neonates is associated with elevated morbidity and mortality. A role for the pro-inflammatory Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is suspected in the innate immune response to bacteria, but little is known about its activities in infants. To begin exploring the feasibility of treating neonatal sepsis by blocking leukocyte TREM-1, we compared TREM-1 membrane expression and mRNA in newborns without clinical or microbiological evidence of infection, to that of healthy adults. The functionality of pro-inflammatory reactions in leukocyte TREM-1 of newborns was also evaluated. METHODS: Twenty term newborns were enrolled in this study and cord blood samples were collected at birth. For comparison, peripheral blood specimens were collected from 20 healthy adults (control adult, CA). The expression of TREM-1 protein and mRNA in leukocytes was detected with flow cytometry and real-time qPCR, respectively. Whole cord blood was also stimulated by Escherichia coli or blocked by the TREM-1-specific peptide LP17 to identify changes in the secretion of pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha, as well as soluble TREM-1 (sTREM-1) using enzyme linked immunosorbent assay (ELISA). RESULTS: Mean fluorescence intensity (MFI) of TREM-1 on leukocytes of newborns appeared comparable to healthy adults [monocytes: 37.5 +/- 6.7 vs. 37.6 +/- 8.7; polymorphonuclear cells (PMNs): 32.9 +/- 6.6 vs. 33.6 +/- 5.8]. However, the percentage of PMNs positive for TREM-1 was lower in newborns than in healthy adults (82.3 +/- 7.1 vs. 98.6 +/- 4.8; P < 0.01); the percentage of TREM-1-positive CD14-positive monocytes was comparable to that of healthy adults (97.1 +/- 8.3 vs. 97.5 +/- 7.4). Exposure of cord blood to E. coli resulted in increased secretion of IL-6, IL-8, TNF-alpha, and sTREM-1. In contrast, the concentrations of IL-6, IL-8, and TNF-alpha decreased by a minimum of 15% when TREM-1 was blocked by LP17 then exposed to E. coli, versus E. coli alone. In addition, the concentration of sTREM-1 was positively correlated with the levels of TNF-alpha (r = 0.519, P < 0.05), IL-6 (r = 0.507, P < 0.05), and IL-8 (r = 0.538, P < 0.05). CONCLUSIONS: Healthy newborns exhibit expression of TREM-1 on monocytes similar to that in healthy adults, and most PMNs express TREM-1 at the newborn stage. Detection of sTREM-1 in neonatal peripheral blood should be further investigated as a potential method for the diagnosis of neonatal infection. Finally, blocking the TREM-1 signal transduction pathway may reduce inflammatory responses of neonate leukocytes and thereby provide a new strategy for treatment of neonatal infection. PMID- 25126162 TI - Camk2b protects neurons from homocysteine-induced apoptosis with the involvement of HIF-1alpha signal pathway. AB - In our previous study using iTRAQ technique we found that the level of calmodulin dependent protein kinase 2b (Camk2b) was lower in rats with hyperhomocysteinemia. We presumed that Camk2b might be involved in homocysteine-induced apoptosis and tried to explore its role in this study through the transfection with Camk2b gene. Results showed that neurons of HHcy group had lower activity measured by MTT, higher percentage of apoptotic neurons, lower expression levels of Camk2b mRNA and protein than those in normal group. Neurons with overexpression of Camk2b (Camk2b group) had lower percentage of apoptosis and higher activity than those in control group. After exposure to 2-Methoxyestradiol, the activity of neurons with overexpression of Camk2b was suppressed with more apoptotic cells observed. The expressions of BCL2, eNOS, EP300 and EPO were all elevated at both mRNA and protein levels in neurons of CamK2b group compared with other three groups. Thus, Camk2b protects neurons from Homocysteine-induced apoptosis with the involvement of HIF-1alpha signal pathway. PMID- 25126163 TI - Radiographical and clinical evaluation of critical size defects in rabbit calvaria filled with allograft and autograft: a pilot study. AB - Regeneration of resorbed edentulous sites can be induced by bone grafts from the subject himself and/or by the use of biomaterials. At present, there has been an extensive search for biomaterials that are evaluated by artificially creating one or more critical defects. The aim of this work was to clinically and radiographically analyze bone formation by the use of some biomaterials in artificially created defects in the parietal bone of rabbits. Six rabbits were used, creating defects of 8 mm in diameter in parietal bones. One defect was maintained with coagulum only, and in others, freeze-dried bone allograft (FDBA), autologous bone, and a combination of autologous bone with FDBA respectively, were added. Animals were sacrificed at 15-90 days with 2 weeks interval each, and calvaria were analyzed macroscopically, measuring by digital caliper the lack of filling at the surface of defects, identifying limits at anteroposterior and coronal view, realizing a digital photograph register of their external surfaces. This was subsequently evaluated radiographically by occlusal film radiography used to quantify its density through software. In conclusion, autologous bone showed the best behavior, clinically as well as radiographically. However, FDBA is a good option as an alternative to autologous bone as its behavior was slightly lower over time. The combination of autologous bone and FDBA in the same defect showed results considerably inferior to grafts used separately. Low radiopacity and clear limits were observed through time for the control coagulum filled defect. PMID- 25126164 TI - Serum M30 and M65 levels and effects of Ankaferd blood stopper in cerulein induced experimental acute pancreatitis model in rats. AB - BACKGROUND AND AIM: The incidence of acute pancreatitis is increasing recently. The aim of this study is to investigate the effect of Ankaferd Blood Stopper (ABS) on experimental model of cerulein induced acute pancreatitis in rats. MATERIALS AND METHODS: Forty Wistar Albino rats were divided into five groups. Group 1: Sham (n = 8), Group 2: Control group (n = 8), Group 3: Treatment group (n = 8), Group 4: Prophylaxis group (n = 8), Group 5: Prophylaxis treatment group (n = 8). Any practice was not administered to Group 1. Rats were treated with either 1 ml ABS or 1 ml saline via intraperitoneal route before and after inducing acute pancreatitis. Pancreatic tissues were examined histopathologically. Amylase, cytokines (tumor necrosis factor-alpha and interleukin-1beta), and markers of apoptosis (M30 and M65) were also measured in blood samples. Immunohistochemical staining was performed with caspase 3 antibody. RESULTS: We found a statistically significant improvement in histopathological scores in treatment group and prophylaxis group compared with controls. In treatment group, M30 and M65 levels were lower when compared with controls. In prophylaxis group, there was not a statistically significant difference in M30 levels, but M65 levels were lower when compared with controls. CONCLUSION: In this experimental acute pancreatitis model, we found high histopathological healing effects of ABS treatment and also prophylaxis. ABS treatment and prophylaxis reduced apoptosis. PMID- 25126166 TI - FRAS1 knockdown reduces A549 cells migration and invasion through downregulation of FAK signaling. AB - Distal metastasis is the major cause of death for the vast majority of lung cancer patients. Many extracellular matrix (ECM)-related molecules are proposed to be associated with the migration and invasion of cancer cells. FRAS1 encodes an ECM protein, however, little is known about its function on tumorigenesis and metastasis of lung cancer. In this work, FRAS1 was silenced by shRNA in non-small cell lung cancer (NSCLC) A549 cell line. The capacities of A549 cells to migrate and invade were decreased markedly after FRAS1 knockdown. The shRNA knockdown of FRAS1 was found to be specific and had no effect on A549 cells proliferation. Western blot experiments demonstrated that FRAS1 knockdown inhibited FAK signaling but not Src signaling. Overall, we found that FRAS1 knockdown reduces A549 cells migration and invasion ability through downregulation of FAK signaling. PMID- 25126165 TI - Celastrol may have an anti-atherosclerosis effect in a rabbit experimental carotid atherosclerosis model. AB - BACKGROUND: Celastrol may have an anti-atherosclerosis effect. This study aimed to investigate if celastrol had an anti-AS effect using a rabbit experimental carotid atherosclerosis model. METHODS: Forty male Japanese white rabbits were divided into the sham group (normal diet), the model group (high fat diet), the group treated with celastrol (high fat diet) and the group treated with atorvastatin (high fat diet) randomly. The rabbits fed a high fat diet underwent balloon injury of the right common carotid artery and were treated with dimethyl sulfoxide (DMSO) (the model group, 3.5 ml/kg/d), celastrol and its dissolvent DMSO (the celastrol group, 1 mg/kg/d and 3.5 ml/kg/d) and atorvastatin and its dissolvent DMSO (the atorvastatin group, 2.5 mg/kg/d and 3.5 ml/kg/d) for 12 weeks by gavage. RESULTS: The ratio of the plaque area and the arterial wall cross-section area in the celastrol group was significantly less than the model group (P < 0.001), and there was no significant difference compared with the atorvastatin group. The serum level of LDL-C of the celastrol group was significantly lower than the model group (P = 0.014), and there was no significant difference compared with the atorvastatin group. The expression of VEGF in the celastrol group was significantly less compared with the model group (P = 0.014), whereas the expression of VEGF in the atorvastatin group and the model group showed no significant differences. CONCLUSION: Our findings suggest that celastrol effectively reduced the plaque ratio, decreased the serum levels of LDL and downregulated the expression of VEGF, suggesting an anti-AS effect of celastrol. PMID- 25126167 TI - Ameliorating effects of CAPE on oxidative damage caused by pneumoperitoneum in rat lung tissue. AB - We investigated the biochemical and histopathological effects of caffeic acid phenethyl ester (CAPE) against oxidative stress causing lung injury induced by pneumoperitoneum. Twenty-eight rats were selected at random and seven rats were assigned to each of the following groups. The control group (S) was subjected to a sham operation without pneumoperitoneum. The other groups were subjected to CO2 pneumoperitoneum 15 mmHg for 60 min. The laparoscopy group (L) had no additional drugs administered, the laparoscopy + alcohol (LA) group had 1 ml of 70% ethyl alcohol administered 1 h before the desufflation period, and the laparoscopy + CAPE (LC) group had CAPE administered at 10 MUmol/kg 1 h before the desufflation period. The total oxidative status levels of lung and plasma were significantly increased in the LA group as compared with the LC and S group. When the LC group was compared with the L group, there was a decrease in the level of total oxidant status and increase in the levels of total antioxidant status and paraoxonase in lung tissue. The level of total antioxidative status in the S group was increased compared with the L group in lung tissue and bronchoalveolar lavage fluid. TNF alpha and IL-6 were found significantly elevated in the L group compared with the LC and S groups in bronchoalveolar lavage fluid. There was a similar increase in plasma levels of IL-6. These results were supported by histopathological examination. CAPE was found to considerably reduce oxidative stress and inflammation induced by pneumoperitoneum. PMID- 25126168 TI - L-3-n-butylphthalide improves cognitive impairment of APP/PS1 mice by BDNF/TrkB/PI3K/AKT pathway. AB - L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn (Chinese celery), has been shown to have neuroprotective effects on cerebral ischemic, vascular dementia and amyloid-beta (Abeta)-induced animal models by inhibiting oxidative injury, neuronal apoptosis and glial activation, regulating amyloid-beta protein precursor (AbetaPP) processing and reducing Abeta generation. The objective of this study was to investigate the effects of L-3-n butylphthalide on memory impairment and the expression of brain neurotrophic derived factor (BNDF), kinaseB (TrkB), phosphatidylinositol 3 kinase (PI3K) and Akt in APP/PS1 double transgenic mouse models. APP/PS1 double transgenic mice were administered 30 mg/kg*d L-NBP and 10 mg/kg*d L-NBP for one month. The learning and memory ability were studied using the water maze test. Protein expression and transcript levels of genes in the mice hippocampus were evaluated using western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. The results demonstrated that both 30 mg/kg*d L NBP and 10 mg/kg*d L-NBP doses of L-NBP significantly increased memory capability and the expression of hippocampal BDNF/TrkB/PI3K/AKT in mice The results suggested that L-NBP treatment may reverse memory impairment in APP/PS1 transgenic mice, and BDNF/TrkB/PI3K/AKT, may be involved in this process. PMID- 25126169 TI - Occlusive barriers in combination with particulate Bio-Oss(r) graft: a pilot study on rabbit calvaria. AB - The aim of this study was to histologically evaluate the potential for vertical bone augmentation of the Bio-Oss(r) graft compared to a blood clot in conjunction with an occlusive barrier in the rabbit calvaria defect model. Metallic dome shaped barriers with 4.5 mm width and 3.5 mm height were positioned in six adult rabbit skulls. At the right side, the barrier was filled with Bio-Oss(r), and the left side was filled with a blood clot. After a healing period of three months, the animals were sacrificed, and the samples were prepared for histological and histomorphometric analyses. The total mineralized area (TMA) as well as the newly formed bone (NBA) was calculated as the percentage of the bone augmentation inside the metallic barriers, and parametric statistical analysis was used to describe the findings. The samples with blood clots exhibited significantly less TMA formation than the Bio-Oss(r) group. However, the difference in the amount of NBA was not statistically significant. Furthermore, the Bio-Oss(r) specimens exhibited remaining graft particles within the sample. In conclusion, the barriers filled with Bio-Oss(r) exhibited significantly higher TMA than those with only blood clots, and the remaining Bio-Oss(r) particles were integrated into newly formed bone tissue to fill the spaces and promote a greater volume than the samples from the blood clot groups. PMID- 25126170 TI - Antibacterial activity of leaf essential oil and its constituents from Cinnamomum longepaniculatum. AB - Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Salmonella enteritidis CMCC (B) 50041, were used in the antibacterial tests of Cinnamomum longepaniculatum leaf essential oil and its five chemical constituents. The effect of 1, 8-cineole on the ultrastructural structure of the bacteria (S. aureus and E. coli) was also investigated by transmission electron microscopy. The C. longepaniculatum leaf essential oil and the five chemical constituents showed variable levels of inhibition. Their MIC ( minimum inhibitory concentration ) and MBC (minimal bacteriocidal concentration) values were all in the range of 0.781 uL/mL~6.25 uL/mL and 0.781 uL/mL~12.5 uL/mL respectively except gamma-terpinene. The MIC values of gamma-terpinene against E. coli and S. aureus were all higher than 50 uL/mL, but the MIC and MBC values of gamma terpinene against S. enteritidis was only 3.125 uL/mL. Among them, alpha terpineol possessed the best antibacterial activity. Under the transmission electron microscope, cell size of treated E. coli decreased, cell wall and cell membrane ruptured, and nucleoplasm was reduced and gathered onto the side. After the S. aureus was treated with 1, 8-cineole, the cell size and shape were damaged and nucleus cytoplasm was concentrated or reduced or agglomerated on the side. These results suggest that C. longepaniculatum leaf essential oil and its constituents have excellent antibacterial activities, the antibacterial mechanism of 1, 8-cineole against E. coli and S. aureus might attributable to its hydrophobicity. PMID- 25126172 TI - Methylation status of promoter 1 region of GDNF gene in human glioma cells. AB - OBJECTIVE: This study aimed to investigate the methylation status of promoter 1 region of glial cell line-derived neurotrophic factor (GDNF) in human glioma cells and to explore the effect of GDNF methylation on the expression of GDNF in glioma. METHODS: GDNF gene mutation was detected by sequencing in 10 patients with glioma and 5 healthy controls. Bisulfite modification for analysis of DNA methylation was done to detect the methylation status of promoter 1 region of GDNF in 20 patients with glioma (10 with poorly differentiated and 10 with well differentiated) and 5 healthy controls. RESULTS: There was no mutation at the promoter 1 region of GDNF gene in glioma. The incidence of methylation of GDNF gene at the promoter 1 region in healthy control, patients with poorly differentiated glioma and those with well differentiated glioma was 72.25%, 86.25% and 86.75%. The incidence of GDNF methylation in glioma was significantly higher than that in the normal brain (P<0.05); while there was no significant difference between well differentiated glioma and poorly differentiated glioma. CONCLUSIONS: Hypermethylation occurs in the promoter 1 region of GDNF and may influence the expression of GDNF in glioma. PMID- 25126171 TI - Accuracy of pulse oximeter perfusion index in thoracic epidural anesthesia under basal general anesthesia. AB - OBJECTIVE: To observe the change of PVI after thoracic epidural block on the basis of general anesthesia. METHODS: In 26 patients undergoing elective upper abdominal operations, changes of SVI, PVI, SVV, PPV and CVP were monitored immediately before and 10 minutes after T8-9 thoracic epidural anesthesia on the basis of general anesthesia. The definition was that patients with DeltaSVI greater than 10% belonged to response group to epidural block. RESULTS: Before epidural block, the PVI, SVV and PPV baseline values in patients of response group were significantly higher than those in patients of non-response group. PVI, SVV and PPV after epidural block were significantly higher than immediately before epidural block (P < 0.001). PVI, SVV and PPV baseline values immediately before epidural block were positively correlated with DeltaSVI; the correlation coefficients were 0.70, 0.71 and 0.63, respectively, P <= 0.001. The optimal critical values for PVI, SVV and PPV to predict response to T8-9 gap epidural block under general anesthesia were 16% (sensitivity 80%, specificity 92%), 13% (sensitivity 90%, specificity 62%) and 12% (sensitivity 90%, specificity 77%), respectively. CONCLUSION: PVI can be used as a noninvasive indictor to monitor volume change after thoracic epidural block on the basis of general anesthesia. PMID- 25126173 TI - Rosiglitazone accentuates the adipogenesis of hemangioma-derived mesenchymal stem cells induced by adipogenic media. AB - Hemangioma-derived mesenchymal stem cells (Hem-MSCs) expressed PPAR-gamma, the key transcription factor in adipogenesis. We supposed that rosiglitazone, the agonist of PPAR-gamma, may promote the adipogenesis of Hem-MSCs. In this study, MSCs were isolated from proliferating hemangioma. Four groups were set up, which were Group A (DMEM-LG/10% FBS), Group B (1 MUM rosiglitazone + DMEM-LG/10% FBS), Group C (adipogenic media), and Group D (1 MUM rosiglitazone + adipogenic media). Cells were cultured in the medium above. On the day 7 and 14, Oil Red "O" staining and Western blot were performed to detect the cytoplasmic lipid and perilipin A in the cells. The results showed that cytoplasmic lipid appeared in Group C and D, and no cytoplasmic lipid in Group A and B on the day 7 and 14. Analysis of Oil Red "O" staining showed the area of staining in Group D was significantly larger than that in Group C. Analysis of western blot showed no expression of perilipin A in Group A and B, and upregulated expression in Groups C and D, with the greater upregulation in Group D. In conclusion, our study demonstrated that rosiglitazone promoted the adipogenesis of Hem-MSCs initiated by adipogenic media via the activation of PPAR-gamma pathway. The results may put forward the possibility of treating hemangioma via PPAR-gamma pathway. PMID- 25126174 TI - Confirming the brain death diagnosis using brain CT angiography: experience in Tokat State Hospital. AB - OBJECTIVE: Fourteen brain death cases diagnosed in Mart 2012-May 2013 period in Tokat State Hospital were studied retrospectively. CT angiography experience about those cases was shared, and use of CT angiography in confirmation of brain death was discussed. MATERIAL AND METHODS: All 14 cases were patients on mechanical ventilator, who did not respond to medical and surgical treatments at intensive care unit and were diagnosed clinically with brain death. All of these patients had CT angiography as a confirmatory test using a 4-slice CT scanner in Radiology department in Tokat State Hospital. FINDINGS: Six of the patients were female and eight were male. All of them were referred from intensive care unit and had clinical brain death diagnosis before CT angiography. In the evaluation of CTA, four-point scoring involving opacification loss in both ICVs and cortical segments of MCA was used. CTA examinations confirmed brain death diagnoses in all patients who had clinical brain death diagnoses, and no confliction between CTA findings and clinical diagnoses was observed. CONCLUSION: Demonstrating the lack of cerebral circulation is a necessity for confirmation of brain death diagnosis. While conventional angiography remains the standard method, CTA emerged as an alternative method. In parallel to increase in prevalence of organ implants, CTA, a fast and efficient method, has been increasingly used in confirmation of brain death diagnoses. PMID- 25126175 TI - A novel approach to locate renal artery during retroperitoneal laparoendoscopic single-site radical nephrectomy. AB - OBJECTIVE: To verify the feasibility and safety of retroperitoneal laparoendoscopic single-site radical nephrectomy and assess the value of our proposed approach to search for renal artery. METHODS: A total of 60 cases of retroperitoneal laparoendoscopic single-site radical nephrectomy were performed using our homemade single-port multi-channel device. An incision of 5-6 cm was cut forward from the posterior axillary line under the lower margin of the 12th rib, and a single-port multi-channel device comprised of two control rings and a No. 7 glove was placed into the incision. Retroperitoneal laparoendoscopic single site radical nephrectomy was then performed via locating renal artery through muscle and ligament on the posterior abdominal. RESULTS: The 60 cases were all successful. None of the 60 patients developed surgical complications. CONCLUSION: The application of homemade device is safe and feasible. Our proposed method is of greater practical significance for the relatively narrow operating space in retroperitoneal laparoendoscopic single-site surgery. PMID- 25126176 TI - Primary malignant melanoma of the lung: a case report. AB - Primary malignant melanoma of the lung is a very rare disease with about 40 cases reported in English literature. We report a 49-year-old female with history of 2 month chest pain who was revealed to have a peripheral lung mass in left upper lobe by chest CT scan. Left upper lobectomy was performed and post-operative pathology revealed to be primary malignant melanoma of the lung. 4 months after operation, a node in right breast was found by patient herself and needle aspiration biopsy revealed to be breast cancer. The patient refused any diagnostic and therapeutic procedure and died of extensive metastasis 3 months later. Primary malignant melanoma of the lung is highly malignant disease with poor prognosis in most patients. PMID- 25126177 TI - Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft. AB - BACKGROUND: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. METHODS: UC MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. RESULTS: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-beta1 and suppressed proinflammatory cytokines IL2 and IFN-gamma in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. CONCLUSIONS: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft. PMID- 25126178 TI - Kinetic analysis of the immunity in a pregnant patient infected with avian influenza H7N9. AB - BACKGROUND: Human infection with avian influenza A H7N9 has emerged in China since February, 2013. The immunologic changes in pregnant women infected with H7N9 are not known. OBJECTIVE: To report the clinical data and kinetic changes of immunity in a pregnant woman infected with H7N9 virus in Zhenjiang, Jiangsu, China. METHODS: The clinical data were collected and immunity status was monitored in this patient. RESULTS: H7N9 virus became undetectable in sputum from 14 days since onset of symptoms after effective antiviral therapy with oseltamivir and symptomatic/supporting treatments. The symptoms and signs in this patient gradually improved from 15 days since onset of symptoms. Peripheral lymphocytes initially decreased and gradually increased. The percentage of CD4+ T cells increased since 16 days after onset of symptoms. The kinetic changes of cytokines including IFN-gamma, IFN-alpha, TNF-alpha, IL-10 and TGF-beta1 matched the development and recovery of illness. Her family members, including her parents exposed to H7N9 positive materials in poultry market, were H7N9 negative. CONCLUSIONS: Our results indicate that pregnant women are susceptible to H7N9 virus and H7N9 infection in pregnant women is curable without significant impact on fetus. Kinetic changes of pro-inflammatory and anti-inflammatory cytokines play a role in the pathogenesis and clinical outcome in the pregnant patient with H7N9 infection. PMID- 25126179 TI - Application status of blood constituents during massive blood transfusion in some regions of China. AB - OBJECTIVE: This study aims to learn about the current situation of surgical massive blood transfusion in China's Class III general hospitals, which could provide the basis for the formulation of guidelines on massive blood transfusion. METHODS: A multicenter retrospective research on the application status of blood constituents during massive blood transfusion was conducted and a comparative analysis on the distribution of the population infused with other blood constituents and the transfusion volume at different periods of time when red blood cells are infused in different units within 24 hours as well as on the blood applied for both the death group and survival group was made in this study. RESULTS: In China, during massive blood transfusion the ratio of the dosage of fresh frozen plasma to the dosage of red blood cell suspension reached 1:1-2, while the dosage of platelet and cryocepitate appeared to be very small. CONCLUSION: During massive blood transfusion, clinicians in 20 Chinese hospitals paid more attention to the infusion of fresh frozen plasma while making the infusion of red blood cells. However, they paid little attention to the supplement of platelet and cryocepitate. PMID- 25126180 TI - Presence of FOXP3(+)Treg cells is correlated with colorectal cancer progression. AB - The transcription factor FOXP3 is specifically expressed in regulatory T (Treg) cells and appears to mediate immune surveillance. Indeed, FOXP3(+)Treg cells have been linked to disease pathogenesis, including some cancers. This study investigated the presence of FOXP3(+)Treg cells in colorectal cancer and the relationship of FOXP3 expression with clinicopathological features of colorectal cancer. Immunohistochemistry was used to detect expression of FOXP3 in 63 samples of colorectal cancer and 20 samples of healthy colorectal tissue; flow cytometry was used to detect FOXP3(+)Treg cells in peripheral blood. FOXP3 was more commonly expressed in colorectal cancer tissues than in normal colorectal tissues (P < 0.05). Similarly, the percentage of FOXP3(+)Treg cells in the peripheral blood was higher in patients with colorectal cancer than in control individuals (P < 0.05). The expression of FOXP3 was positively correlated with gender, Dukes staging, and lymph node metastasis. Further, expression increased with the increasing degree of malignancy (P < 0.05). Thus, FOXP3 expression may represent a valuable index in evaluating the degree of malignancy, clinicopathologic staging, and lymph node metastasis in colorectal cancer. Further, detection of FOXP3(+)Treg cells may be useful in predicting invasion, metastasis, and prognosis of patients with colorectal cancer. PMID- 25126181 TI - Aberrant sonic hedgehog signaling pathway and STAT3 activation in papillary thyroid cancer. AB - The sonic hedgehog (SHH) and STAT3 signaling pathways play important roles during carcinogenesis with possible interaction. To determine the association of the activation of SHH signaling pathway and STAT3 pathway in carcinogenesis of human papillary thyroid cancer (PTC), we examined the expression of SHH signaling pathway molecules including SHH, Patched (PTCH), Smoothened (SMO) and GLI1 (glioma-associated oncogene homolog 1), as well as p-STAT3 (phosphorylation at Tyr705) by immunohistochemistry in 164 cases of PTC. In PTC, 70.12%, 64.02%, 68.90%, 64.02%, and 56.71% and in the adjacent normal thyroid tissues, 18.29%, 18.90%, 26.83%, 14.63%, and 10.98% of the specimens stained positive for SHH, PTCH, SMO, GLI1, and p-STAT3, respectively. Significant difference were found for the positive rate of SHH, PTCH, SMO, and GLI1 as well as p-STAT3 expression between PTC and adjacent normal thyroid tissues. There was a high accordance rate between SHH, PTCH, SMO, and GLI1 expression and all of them positively correlated with larger tumor size, the presence of ETE and LNM, and higher TNM stage. P STAT3 expression positively correlated with the presence of ETE and LNM, and higher TNM stage but not age, gender, tumor size of the PTC patients. Signifi cant positive correlation between p-STAT3 and SHH, PTCH, SMO and GLI expression was found in PTC. These findings suggest that the SHH and STAT3 signaling pathways are frequently activated in PTC, interact with each other and may therefore be indicators for prognosis or potential targets for therapy against PTC. PMID- 25126183 TI - Serum endocan levels in patients with chronic liver disease. AB - BACKGROUND AND AIM: Early detection of fibrosis should be the main goal of treatment in liver cirrhosis. Endocan, previously called endothelial cell specific molecule-1, is expressed by endothelial cells, primarily in the lung, liver and kidney. In this study, we aimed to examine the correlation of liver fibrosis stage, histological activity and grade of steatosis between serum levels of endocan in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: This cross sectional study includes a total of 146 subjects. 55 CHB patients, 19 CHC patients, 38 NAFLD patients and 34 healthy controls were enrolled consecutively. Liver biopsies were performed in all patients with chronic viral hepatitis. NAFLD patients had either grade 2 or grade 3 steatosis on ultrasonography and elevated liver enzymes above the upper normal limits. Serum endocan levels were assessed from blood samples obtained at admission. RESULTS: Gender distribution was similar among the groups (p=0.056). The mean age of the CHB patients was 45.8+/ 12.1, CHC patients was 55.0+/-12.8 years, NAFLD patients was 42.8+/-10.8, while control group was 39.4+/-13.6 years old. Patients with CHC were older than all the others (p=0.001). Serum endocan levels were statistically significantly lower in CHB, CHC and NAFLD groups when compared with controls. Although levels of endocan were lower in CHB and CHC groups when compared with NAFLD group, the difference was not statistically significant. CONCLUSION: Serum endocan concentrations decrease in patients with liver disease. Unlike previous studies, we showed a negative correlation between endocan levels and inflammation stage of chronic hepatitis. However, further studies are needed to establish the association between endocan levels, liver fibrosis and hepatic inflammation. PMID- 25126182 TI - Association of epicardial adipose tissue, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with diabetic nephropathy. AB - BACKGROUND: The relationship between diabetic nephropathy, visceral adipose tissue (VAT), and inflammation has been shown. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are simple, inexpensive, and useful markers to determine inflammation. However, to date, in the literature, there have been no studies demonstrating the relationship between epicardial adipose tissue (EAT), inflammation, and albuminuria. AIMS: We aimed to investigate the association between diabetic nephropathy, NLR, and PLR as inflammatory markers and EAT thickness. METHODS: This was a cross-sectional study involving 200 diabetic patients. The patients were separated into three groups according to their albuminuria levels. The NLR and PLR were calculated from a complete blood count. EAT was measured by transthoracic echocardiography. The estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease (MDRD) equation. RESULTS: Disease duration, EAT, creatinine, NLR, PLR, absolute neutrophil, lymphocyte, and platelet count tended to increase with increasing albuminuria while the eGFR decreased. When patients were separated into two groups according to NLR and PLR medians, albuminuria levels increased with an increase of the NLR (p = 0.003) and PLR (p = 0.009). A correlation analysis showed that albuminuria was significantly correlated with EAT, disease duration, creatinine, eGFR, PLR, and NLR levels. Additionally, in a binary logistic regression analysis, EAT, NLR, and PLR were found to be independently associated with albuminuria. CONCLUSIONS: Determining various inflammatory cytokines and measuring abdominal VAT in diabetic patients is complex and expensive. Simply measuring EAT and calculating NLR and PLR can predict inflammation and albuminuria in patients with diabetes. PMID- 25126184 TI - Clinical significance of methylation of E-cadherin and p14ARF gene promoters in skin squamous cell carcinoma tissues. AB - Epigenetic regulation of genes by DNA methylation contributes to cancer. The present study sought to identify methylation changes in the promoters of E cadherin and p14ARF, two genes with potential cancer roles promoting in skin squamous cell carcinoma. Skin squamous cell carcinoma specimens were collected from 40 patients and normal skin tissues were collected from 30 individuals as controls. Promoter methylation was detected for E-cadherin and p14ARF by methylation-specific PCR. Correlations between E-cadherin or p14ARF methylation and clinicopathological parameters were analyzed by the Spearman rank test. Methylation of E-cadherin (37.5%) and p14ARF (60.0%) was significantly more common in skin squamous cell carcinoma than in normal skin tissue (10.0 and 6.7%, respectively; P < 0.05). Additionally, E-cadherin and p14ARF methylation were positively correlated within skin squamous cell carcinoma (r = 0.422, P = 0.007). Furthermore, methylation of these gene promoters in skin squamous cell carcinoma was correlated with differentiation, lymph node metastasis, and clinical stage (P < 0.05). Aberrant methylation in promoters of E-cadherin and p14ARF may promote occurrence and progression of skin squamous cell carcinoma. PMID- 25126185 TI - An miR-143 promoter variant associated with essential hypertension. AB - MicroRNAs like miR-143 are increasingly linked to disease pathogenesis. miR-143 is enriched in vascular smooth muscle, and several single nucleotide polymorphisms have been identified in this miRNA. The aim of the current study was to explore a potential correlation between a polymorphism in the miR-143 promoter region, rs4705342, and essential hypertension (EH). Genotyping for miR 143 rs4705342 was performed from blood samples of 156 EH patients (case group) and 187 healthy individuals (control group) using a TaqMan assay. Participant demographic and clinical characteristics were also collected. Logistic regression was used to identify an association between genotype and EH, and odds ratios of EH risk were also determined. Frequencies of the CC, CT, and TT genotypes differed significantly between case (7.7%, 40.4%, 51.9%) and control (15.0%, 48.1%, 36.9%) groups (chi(2) = 9.400, P = 0.009). Further, the frequency of the C allele was lower in the case group than in the control group (27.9% vs. 39.0%, P = 0.002). Compared with those having the TT genotype, patients carrying the CC and CT genotypes had a significantly reduced risk for EH (OR = 0.541, 95% CI = 0.351-0.834, P = 0.005), particularly for females, nonsmokers, and those not consuming alcohol (P < 0.05). Thus, the rs4705342 polymorphism in the miR-143 appears to be associated with essential hypertension, and further study is needed to understand the molecular mechanism producing this effect. PMID- 25126186 TI - Responsibility and burden from the perspective of seniors' family caregivers: a qualitative study in Shanghai, China. AB - OBJECTIVES: This study aimed to explore the experience of seniors' family caregivers with regarding the responsibility, burden and support needs during caregiving in Shanghai, China. MATERIALS AND METHODS: An exploratory, descriptive, qualitative design was used and a semi-structure interview was conducted. A convenience sample of 11 participants in two community service centers in Shanghai was recruited. Data saturation guided the size of the sample. The Colaizzi method of empirical phenomenology was used for interviewing and analyzing data obtained from 11 caregivers. RESULTS: Three major themes were found: It is a hard work; It is my responsibility; Social support is not enough. CONCLUSION: The findings of the study are practical and helpful for health care providers to develop appropriate caregiver support services, to balance the responsibility and burden of caregivers, and to consider the factors influencing the utility of support services. PMID- 25126187 TI - Prevalence of prostatitis-like symptoms in outpatients with four premature ejaculation syndromes: a study in 438 men complaining of ejaculating prematurely. AB - OBJECTIVE: To evaluate the incidence of prostatitis-like symptoms (PLS) in men with or without PE, and the differences among the 438 outpatients with the four PE syndromes. SUBJECTS AND METHODS: Between January 2012 and January 2013, 438 consecutive heterosexual men complaining of PE and another 493 male healthy subjects without the complaint were included in this study. Each of them completed a detailed face-to-face questionnaire for information of demographics, National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), and International Index of Erectile Function-5 (IIEF-5). Each patient was classified as one of the four PE subtypes: lifelong PE (LPE), acquired PE (APE), natural variable PE (NVPE), or premature-like ejaculatory dysfunction (PLED). RESULTS: There were no significant difference between patients and control subjects regarding demographics. In the PE group, the prevalence of PLS were 32%, showing statistical significance compared with control subjects (15.8%, P<0.001). And the NIH-CPSI score was 10.0+/-7.9, showing significant difference compared with control subjects (6.0+/- 5.4, P<0.001). Among the four PE syndromes, patients with PLED had the highest prevalence of PLS (42.3%, P<0.001), but the difference of NIH-CPSI scores among the four PE syndromes was not significant (P=0.055). CONCLUSIONS: PLS were more common in patients with PE. Also, patients had worse NIH-CPSI scores than the control subjects. Therefore, patients with PLED had the highest incidence of PLS. PMID- 25126188 TI - Risk factors target in patients with post-thyroidectomy bleeding. AB - As the highly blood flow of thyroid gland post-thyroidectomy bleeding (PTB) is a serious and life-threatening complication. Our aim was to investigate factors that influenced bleeding after thyroidectomy. Between February 2008 and September 2012, the data of 4449 consecutive patients with thyroid diseases undergoing thyroidectomy were collected and analysed from the department of surgical oncology retrospectively. During the study period, 88 (2.0%) patients were identified to have clinically PTB. 6 risk factors were significantly related to PTB: gender (OR 3.243; 95% CI 2.078-5.061; P < 0.001), age (OR 1.025; 95% CI 1.006-1.043; P = 0.009), tumor size (OR 4.495; 95% CI 2.462-8.208; P < 0.001), postoperative hypertension (OR 2.195; 95% CI 1.006-1.043; P = 0.035), lymph node dissection (OR 3.384; 95% CI 2.146-5.339; P < 0.001) and Graves' disease (OR 3.744; 95% CI 1.920-7.303; P < 0.001). We addressed the most common explicit source of bleeding by reexploration: infrahyoid muscles (30/88), beside the laryngeal recurrent nerve (22/88), subcutaneous tissue (10/88) and superior pole (10/88). In our study, male gender, older age, tumor size > 3 cm, postoperative hypertension (SP > 150 mmHg), lymph node dissection and Graves' disease were independent risk factors for PTB. The sources of bleeding were identified more frequently in the infrahyoid muscles and beside the laryngeal recurrent nerve. It is helpful for surgeons to decide the potential bleeding points during the reexploration of PTB. PMID- 25126189 TI - Gene profiling analysis for patients with oral verrucous carcinoma and oral squamous cell carcinoma. AB - Oral verrucous carcinoma (OVC) is one malignant tumor which was carved out from the oral squamous cell carcinoma (OSCC). However, the clinical and pathological features as well as the treatment strategies of OVC are different from OSCC. Here, global transcript abundance of tumor tissues from five patients with primary OVC and six patients with primary OSCC including their matched adjacently normal oral mucosa were profiled using the Affymetrix HGU133 Plus 2.0. Ingenuity Systems IPA software was used to analyse the gene function and biological pathways. There were 109 differentially expressed genes (more than 2-fold) between OVC and the adjacently normal tissue, among them 66 were up-regulated and 43 were down-regulated; 1172 differentially expressed genes (2-fold) between OSCC and the adjacently normal tissue, among them 608 were up-regulated and 564 were down-regulated. There were 39 common differentially expressed genes in OVC and OSCC compared with their matched normal oral mucosa, among them 22 up-regulated and 17 down-regulated, and 8 of them different between OVC and OSCC. In addition, the gene expression profile was further validated by quantitative real-time PCR (Q-RT-PCR) analysis for four of those 39 selected genes. PMID- 25126190 TI - Effect of lower than expected number of oocyte on the IVF results after oocyte pickup. AB - OBJECTIVES: To investigate whether a lower than expected number of oocyte after >=14 mm follicle aspiration during OPU has any effect on pregnancy outcomes Methods: This is a retrospective study done between 2010 and 2013 at the IVF Unit of the Zeynep Kamil Women and Children Diseases Education and Research Hospital, dealing with the medical records of infertile patients who underwent IVF cycle and controlled ovarian stimulation with long agonist or fix antogonist protocol. The patients included into the study were those diagnosed with a primary infertility, aged between 23 and 39, at a BMI of 22-28 kg/m(2) and having received the first or second IVF treatment. Male factor, presence of uterine anomaly, patients with serious endometriosis and patients with low ovarian reserve were all excluded from the study. Typically, oocyte pick-up was performed in all the patients 35.5 hours after the hCG implementation. Single or double embryo transfer was performed, where available. Patients were classified into two groups. Group 1 consisted of those with no difference between >=14 mm aspirated follicle number and expected number of oocyte or with 1 missing number of oocyte at the most. Group 2 consisted of those with at least >=2 missing number of oocyte between aspirated follicle number and expected number of oocyte. Statistical analysis was performed using Student's t test for continuous variables and chi-square test for categorical variables. Additionally, a Linear regression analysis was conducted between the total number of oocyte and pregnancy. RESULTS: In total, 387 treatment cycles were included into the study. Group 1 consisted of 134 patients and Group 2 consisted of 252 patients. Antral follicle number (12.8 +/- 4.3 and 14.5 +/- 4.1, P = 0.0007), hCG day E2 value (1990.7 +/- 1056.4 and 2515.2 +/- 1332.7, P < 0.0001) and the the number of aspirated follicle during OPU (9.1 +/- 4.4 and 13.7 +/- 5.5, P < 0.0001) were significantly higher in Group 2; whereas on the other hand, daily gonadotropin dose (290.9 +/- 79.9 and 273.4 +/- 74.4, P = 0.034) and total gonadotropin doses (2545 +/- 1031.8 and 2247.7 +/- 901.9, P = 0.004) were significantly higher in Group 1. The pregnancy rate was significantly higher in Group 1 (29.1% and 19.4%, P = 0.041). No correlation was observed between the number of oocyte and pregnancy (r = 0.082, P = 0.107). CONCLUSIONS: The number of aspirated follicles during IVF treatment being higher than the collected number of oocyte leads to a statistically significant fall in the pregnancy rates. There is no correlation between the number of oocyte and pregnancy. PMID- 25126191 TI - Effect of male hepatitis B virus infection on outcomes of in vitro fertilization and embryo transfer treatment: insights from couples undergoing oocyte donation. AB - It is common to see HBV infected couple seeking fertility treatment in reproductive medical centers. However, it is still unclear whether HBV infection has any relationship with IVF outcome. To assess the impact of male HVB infection on the outcomes of IVF, we retrospectively analyzed data from two hundred and seventy-seven subfertile couples undergoing oocyte donation cycles in our center. Twenty men (7.2%) were HBV seropositive in 277 couples. 20 couples with seropositive husbands had similar semen parameters and fertilization rate when compared with their controls. Among the 215 couples undergoing their first oocyte donation cycles, 19 couples with seropositive husbands/seronegative wives had lower implantation rate (26.7% vs. 40.6%; P > 0.05), and lower clinical pregnancy rate (42.1% vs. 63.8%; P > 0.05), but the difference was not statistically significant. In binary regression model, male HBV infection had no association with clinical pregnancy. Our study shows that male HBV infection has little impact on IVF outcomes. PMID- 25126192 TI - Injection of MTX for the treatment of cesarean scar pregnancy: comparison between different methods. AB - The aim of this study was to analyze clinical treatment and outcome of injection MTX for Cesarean scar pregnancy (CSP). We use retrospective study to compare the time in CSP of blood chorionic gonadotropin (beta-HCG) and progesterone drooped to the normal, blood flow resistance and hospitalization days. 34 patients diagnosed with CSP were reviewed in our department from 2000 to 2013, including clinical characteristics, early diagnosis, treatment methods and treatment outcome. All patients were divided into B ultrasound-guided gestational MTX inject group (Group one), local intramuscular treatment group (Group two) and uterine artery perfusion MTX group (Group three). All cases had responded well to treatment. Except three cases of local intramuscular serum beta-HCG decreased slowly MTX 10 mg intramuscular again, the average serum beta-HCG decline of 65% the 4th day after treatment. In intramuscular group, the average length of stay is 19 +/- 2.1 days. Serum beta-HCG, progesterone recovery time were 20 to 89 days, an average of 54.5 days. B ultrasound-guided group hospital stay were 15 +/ 3.1 days, serum beta-HCG, progesterone recovery time were 18 to 71 days, an average of 44.5 days. In Uterine artery embolization group, the average length of stay is 16 +/- 2.4 days, serum beta-HCG, progesterone recovery time were 20 to 70 days, an average of 45 days. Statistical data results using T-test and chi-square test analysis. Three groups of beta-HCG, progesterone decreased to normal days the difference was statistically significant (P < 0.05), but uterine artery embolization group and ultrasound-guided group B showed no significant difference (P > 0.05). B ultrasound-guided gestational injection of MTX and uterine artery embolization perfusion MTX are the better ways to treat uterine scar pregnancy. PMID- 25126193 TI - Combined effects of astragalus soup and persistent Taiji boxing on improving the immunity of elderly women. AB - OBJECTIVE: To observe the combined effects of astragalus soup and persistent Taiji boxing on improving the immunity of women of advanced years. DESIGN: 120 elderly women lacking daily exercise were chosen as the study subjects. By using the table of random numbers, they were then divided into the control group and the experiment group, consisting of 60 each. The control group practiced Taiji boxing for 45 minutes twice a day. The experiment group did the same, and, in addition, took astragalus soup after each boxing. Indexes related to physical immunity of the two groups were observed and compared when they were first chosen, when the alternative treatment was applied three, six and twelve months later, respectively. RESULTS: The two groups demonstrated no significant differences in general data and research indexes when chosen (P > 0.05). Three months after the two groups were chosen and treated differently, the control group demonstrated no significant improvement while most indexes of the experiment group improved considerably (P > 0.05). After six months, the related indexes of both groups improved substantially (P < 0.05) and the improvement with the experiment was even clearer (P < 0.05). Twelve months later, the improvement with the experiment group was more noticeable (P < 0.01 or P < 0.05). CONCLUSIONS: In a relatively short period of three months, Taiji boxing produces no noticeable effect on the improvement of immunity in elderly women. However, when they resume the exercise for another three months and longer, Taiji boxing has a noticeable advantage and the effect is the most favorable when it is combined with astragalus soup. PMID- 25126194 TI - Pentacam could be a useful tool for evaluating and qualifying the anterior chamber morphology. AB - OBJECTIVE: This study aims to investigate the changes of anterior chamber morphology after laser peripheral iridotomy (LPI) in primary angle-closure (PAC) patients using Pentacam. METHODS: 35 normal persons and 35 patients of PAC before and 1 week after neodymium: yttrium: aluminum garnet (Nd: YAG) LPI were evaluated with Pentacam. We measured the anterior chamber angle (ACA), central anterior chamber depth (CACD), peripheral anterior chamber depth (PACD), anterior chamber volume (ACV) and pupil diameter (PD). Paired t-test was used to investigate the differences in anterior segment parameters before and after LPI. Independent samples t-test was used to compare these parameters between PAC patients after LPI and normal persons. RESULTS: There were significant differences between PAC patients and control in nasal and temporal ACA, PACD, ACV (P < 0.05) except for superior (P = 0.053) and inferior ACA (P = 0.389), CACD (P = 0.453) and PD (P = 0.221). ACV increased 56.5% in PAC patients after LPI whose ACV < 57 mm(3), which was more greatly than those patients whose ACV > 57 mm(3) (P = 0.001). CONCLUSIONS: The changes of anterior chamber parameters after LPI in PAC eyes can be demonstrated by Pentacam objectively and quantitatively. LPI seems more effective for PAC eyes with smaller ACV. The anterior chamber parameters in PAC eyes after LPI are still significantly smaller than those of normal persons. PMID- 25126195 TI - Respiratory symptoms and pulmonary function tests in security and safety products plant workers. AB - OBJECTIVE: Lock and key factory workers are under the risk of metal pneumoconiosis and occupational asthma. In this cross-sectional study, it's aimed to evaluate the relationship between metal dust exposure and respiratory symptoms, pulmonary function tests of workers in different section of lock and key factory. METHODS: 54 male workers (mean age, 32.8 +/- 5.4) in a security and safety products plant were evaluated for respiratory symptoms, pulmonary function tests and smoking habits. Results have been interpreted by comparison of the painting (28/54) and grinding group workers (26/54). RESULTS: There was no significant difference between painting (32.1 +/- 4.8) and grinding (33.6 +/- 6.1) groups regarding mean age (P > 0.05). Smokers were in significantly higher in grinding group (18/26). Cough and sputum were reported 14.3% (4/28) in painting and 3.8% (1/26) in grinding workers (P > 0.05). Chest tightness was seen in 7.1% and 7.7% of painting and grinding workers, respectively (P > 0.05). But no chest tightness was reported in both groups when they were away work. Breathlessness was seen in 10.7% and 7.7% of painting and grinding workers, respectively (P > 0.05). Breathlessness was similar in both groups (7.1% vs. 3.8%) when they were away work. When comparing painting and grinding workers respiratory functions no significant difference observed. Chest radiography in painting and grinding workers showed hyperlucency (3.6% vs.11.4%), respectively. CONCLUSION: Painting groups in lock and key factory workers had more but statistically insignificantrespiratory complaints. Interestingly, chest tightness was only observed when both groups were at work. It was thought that ventilation and using personal protective equipment in factory could provide significant benefits. PMID- 25126196 TI - Clinical efficacy of Xinkeshu Pian on coronary heart disease and mood disorder complications after PCI. AB - AIM: To assess the efficacy and safety of combining Xinkeshu tablet treatment with routine Western medicine treatment for patients with coronary heart disease (CHD) and mood disorders after PCI postoperative period. METHOD: 100 patients were randomly divided into treatment group of 50 cases, and control group of 50 cases. The control group was given routine Western medical treatment, whereas the treatment group was given routine Western medical treatment in combination with Xinkeshu tablets. Eight weeks after treatment, the patients underwent SF-36 life quality evaluation, self-rating depression scale (SDS) evaluation, and self rating anxiety scale (SAS) evaluation. RESULT: After the eight-week treatment, the SF-36 life quality scores, SAS scores, SDS score, as well as the reduction in heart creatinine levels of the two groups were compared. The results show statistical significance (P<0.05). CONCLUSION: Xinkeshu can effectively address the PCI postoperative mood disorders in patients with coronary heart disease and improve the quality of life. PMID- 25126197 TI - Pulmonary epithelioid hemangioendothelioma coexisting with pulmonary nodular amyloidosis: case discussion and review of the literature. AB - A 38-year-old female was found to have multiple bilateral lung nodules in a routine chest X-ray examination. Thoracoscopy was performed with biopsy of three nodules from the right lower lobe and Congo red staining showed typical amyloid pattern. Initial diagnosis of pulmonary nodular amyloidosis was made. However, one nodule in the right upper lobe enlarged as detected by follow-up CT scan. The patient underwent F-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET)/CT and a significant high FDG uptake in the largest nodule in right upper lobe was observed while the uptake was normal or mildly increased in the other nodules. Meanwhile, right hilar and mediastinal lymph nodes adenopathy was noted. Right upper lobe was resected by thoracotomy. Surprisingly, histopathological findings showed pulmonary epithelioid hemangioendothelioma (PEH) with metastasis of hilar and mediastinal lymph nodes. To our knowledge, this is the first described case of PEH coexisting with pulmonary nodular amyloidosis. PMID- 25126198 TI - Primary mediastinal adenocarcinoma originating from a calcified nodule. AB - Primary mediastinal adenocarcinoma is rare, but its originating from a calcified nodule is even more unusual. We present herein a 55-year-old female with a superior mediastinal mass, first discovered 2 years prior that changed dramatically from its original appearance as a calcified nodule. The mass was completely resected, and histopathological examination revealed a primary adenocarcinoma. The patient has been disease-free for over 13 months since surgery. To the best of our knowledge, this is the first reported case of mediastinal adenocarcinoma to demonstrate such a surprising course of development. PMID- 25126200 TI - Use of improved tracheal catheters in patient of tracheostomy tube-induced tracheoesophageal fistula: a case report. AB - Tracheostomy tube might cause tracheoesophageal fistula (TEF) due to high cuff pressure or direct mechanical trauma. Surgical repair provides the ideal way to deal with TEF but it necessitates the weaning the patient from mechanical ventilation. Here we report a spontaneous closure of TEF by managing it with improved tracheal catheters in a patient who is dependent on mechanical ventilation. PMID- 25126199 TI - Successful treatment of polymorphic post-transplant lymphoproliferative disorder after allo-HSCT with reduction of immunosuppression. AB - Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication for recipients of solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). In SOT recipients, who previously have a normal immune system that has been immunosuppressed, reduction of immunosuppression (RI) shows favorable outcome. However, in HSCT recipients, who have been profoundly immunosuppressed and for whom the tempo of immune reconstitution cannot be fast enough to eliminate the lymphoproliferative process, RI is ineffective in most patients. Therefore, cases of tumor regression via RI alone are rare in the setting of HSCT. We present a case of 26-year-old female developing a polymorphic B-cell PTLD 4 months after receiving allo-HSCT for T cell lymphoblastic lymphoma. RI alone led to regression of the nasopharyngeal tumor, and no sign or evidence of graft-versus-host disease (GVHD) after RI was observed. The general condition of this patient was quite well just before we submitted our draft. To our knowledge, this is the first case that tumor of PTLD regressed upon RI alone with a favorable prognosis and without any evidence of GVHD and relapse of PTLD after RI therapy in the setting of HSCT, which justify the possible advantage of RI alone for low-risk patients. PMID- 25126201 TI - Diagnostic and prognostic roles of DOG1 and Ki-67, in GIST patients with localized or advanced/metastatic disease. AB - AIM: Gastrointestinal stromal tumor is the most common mesenchymal neoplasia in the gastrointestinal tract and has a broad spectrum of pathological patterns and also clinical features changing from benign to malignant. Although the well characterized parameters to predict the outcome have been the size and the mitotic index of the tumor in the patients with early-staged disease, bulky recurrent or metastatic tumor, resistance to medical treatment and mutation analysis are the prognostic factors for advanced stage-GIST. The aim of this study is to investigate new and more practical tissue markers, such as DOG1 and Ki-67 to specify the GIST diagnosis and also to predict the outcome in GIST patients with both localized and advanced staged disease. METHODS: For the last 14 years, from 1999 to 2013, 111 patients with a histopathological GIST diagnosis from the hospital files were enrolled to the study. In their parafin-embedded tissue samples, DOG1 and Ki-67 expressions were evaluated with immunohistochemisty by two independent pathologists from Cukurova University Medical Faculty. Patients were divided into two groups, the patients with localized disease treated by surgery and the patients with advanced/metastatic disease. DOG1 and Ki-67 expressions were corelated with other diagnostic and prognostic histopathological markers and also the clinical outcome in these two group of patients. RESULTS: The specificity and the sensitivity of DOG1 in GIST diagnosis was found 94 and 43%, respectively. DOG1 expression was especially important in the diagnosis of c-kit negative cases. Although Ki-67 was not found a statistically significant prognostic factor for overall survival, it was strongly corelated with mitotic index which is a well-known standart prognostic factor for localized disease. DISCUSSION: DOG1 seems to be an important diagnostic tool for clinically suspected GIST diagnosis in both advanced or early staged patients whose tumours are c-kit expression negative. On the other hand, Ki-67 can be a stronger candidate for prognostic factor instead of mitotic index to identify the proliferative cells out of mitotic phase but this statement needs be prospectively validated on studies with large number of patients. PMID- 25126202 TI - Vitamin A supplementation alleviates extrahepatic cholestasis liver injury through Nrf2 activation. AB - AIM: To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats. METHODS: Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays. RESULTS: Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1. CONCLUSION: Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats. PMID- 25126204 TI - What kind of healthcare debate do we want? PMID- 25126205 TI - Welcome to our community. PMID- 25126206 TI - Creating a 21st-century intelligent health system. AB - In most areas of life, Americans enjoy the ease and convenience offered by advances in technology, communications, and transportation. Every day we experience the 21st-century model of America, which is one of effectiveness, accuracy, speed, flexibility, efficiency, lower cost, more choices, and greater achievement. We can shop online, compare prices for goods and services, and when decisions need to be made, we have access to a wide array of information sources to assist in making those decisions. In short, Americans enjoy great latitude in our power to determine what is best for us. This is not, however, the case when it comes to health and healthcare. In our current healthcare system, individuals are dependent on a structure that has resisted the natural progress and modernization achieved by market-oriented, 21st-century industries. The information age has been leaving health behind. Although it is the nature of a science- and technology-based entrepreneurial free market to provide more choices of higher quality at lower cost, in the healthcare sector, prices continue to rise, quality is inconsistent, and individuals lack the information, incentives, and power to make choices. PMID- 25126207 TI - Medicare Coverage Strategies: Impact of the MMA and PBMs. AB - American Health & Drug Benefits TM has been created to act as an ideological melting pot focusing on health and drug benefit decision makers, as well as those who may affect or may be affected by those decisions. By engaging in conversations with payors, regulators, employers, and other stakeholders, our journal hopes to enable decision makers to view the impact of benefit designs from as many perspectives as possible. Through this open dialogue, we hope that better decisions may be made, and that the greater healthcare marketplace will be positively impacted. In following our editorial mission, American Health & Drug Benefits TM has sought thought leaders who have influenced and will continue to influence the healthcare marketplace. During a fall visit to Washington, DC, Dr. Joseph Antos was kind enough to host a visit to the American Enterprise Institute and provide his thoughts to Robert Henry, editor-in-chief, on how the Centers for Medicare & Medicaid Services (CMS) exerts its influence on drug coverage in the wake of the Medicare Modernization Act (MMA) and in the face of evidence-based medicine standards. Following a chronology of CMS's role from its inception to current events, Dr. Antos offers a lively insight into CMS's strategy and its tactical effects on the American healthcare system. PMID- 25126208 TI - Role of NCCN in Integrating Cancer Clinical Practice Guidelines into the Healthcare Debate. AB - Many new drugs and drugs in the pipeline are referred to as targeted therapy. Targeted therapies have revolutionized the care of certain cancers, such as chronic myelogenous leukemia, but for other common malignancies, such as colon cancer, the impact on survival has been more modest. These seemingly incremental improvements coupled with the high cost of targeted therapy have focused the debate about the cost of healthcare squarely on oncology. Clinical practice guidelines are a common baseline starting point for this debate. Guidelines reflect clinical evidence and expert judgment, which is necessary to fill in the gaps when clinical evidence is not yet available or is evolving quickly. In addition, clinical guidelines inform other key aspects of oncology care, such as establishing a standard of care, which can then be translated into quality measures. Guidelines can also be reformatted to create an oncology drug compendium or rewritten to provide patient information. PMID- 25126209 TI - Measuring the value of treatment to patients: patient-reported outcomes in drug development. AB - Patient-reported outcomes (PROs) can be important measures of the impact and value of new drug treatments to patients. Recently, both multisector stakeholder groups and the U.S. Food and Drug Administration have carefully considered and issued guidance on best practices for the use of PROs in measuring treatment impact. When best practices are followed and PRO data are appropriately included in drug development strategy and clinical trials, these data can be part of the evidence submitted for drug approval and included in drug labeling. One study showed that PRO data were included in 30% of a sample of new drug labels and were more concentrated in certain therapeutic areas, such as anti-inflammatory agents, vaccines, gastrointestinal agents, and respiratory and urologic agents. PRO data included in labeling, or generated in a similar scientific manner, may often then be used in other communication vehicles, such as formulary submission dossiers, journal or direct-to-consumer advertisements, publications, or continuing medical education. Meaningful and reliable PRO results regarding the effects of new treatments on how patients feel and function provide useful information to those who must make decisions about the availability and utilization of such treatments. PMID- 25126210 TI - Approvable letters in 2007 and the outlook for 2008. PMID- 25126203 TI - The beneficial effect of melatonin in brain endothelial cells against oxygen glucose deprivation followed by reperfusion-induced injury. AB - Melatonin has a cellular protective effect in cerebrovascular and neurodegenerative diseases. Protection of brain endothelial cells against hypoxia and oxidative stress is important for treatment of central nervous system (CNS) diseases, since brain endothelial cells constitute the blood brain barrier (BBB). In the present study, we investigated the protective effect of melatonin against oxygen-glucose deprivation, followed by reperfusion- (OGD/R-) induced injury, in bEnd.3 cells. The effect of melatonin was examined by western blot analysis, cell viability assays, measurement of intracellular reactive oxygen species (ROS), and immunocytochemistry (ICC). Our results showed that treatment with melatonin prevents cell death and degradation of tight junction protein in the setting of OGD/R-induced injury. In response to OGD/R injury of bEnd.3 cells, melatonin activates Akt, which promotes cell survival, and attenuates phosphorylation of JNK, which triggers apoptosis. Thus, melatonin protects bEnd.3 cells against OGD/R-induced injury. PMID- 25126211 TI - The 2007 Pharmaceutical and Biotech Pipeline Year-End Summary: What it Says About the State of the Art of Discovery & Development. PMID- 25126212 TI - Risk factors, subjectivity, and truth in healthcare. PMID- 25126213 TI - Patent reform proposals raise the stakes for researchers, manufacturers of biologics. AB - When the founding fathers provided for patents in the American Constitution, they could hardly have envisioned the 21st-century demands the U.S. Patents and Trademarks Office (PTO) face today. The PTO is an institution that is, by definition, concerned with the new-one essential element of a patent is novelty; however, it is also struggling to fit the needs of modern biotech research and development within a framework conceived by the young American government in the 18th century. In their new book Biotechnology and the Patent System (AEI Press, Washington, DC, 2007), Claude Barfield, PhD, and John Calfee, PhD, both Resident Scholars at the American Enterprise Institute, Washington, DC, discuss reforms being considered by legislators, lawyers, and members of the biotechnology industry that could modernize the patent system and make it work for all the stakeholders. The proposed reforms include changing the way patent applications are filed and pursued, limiting encumbrances that slow the application process, providing more funding to the PTO to speed consideration of applications, granting interested parties the right to intervene while a patent application is being considered, and limiting the administrative and economic burdens associated with the mushrooming numbers of patents for each product or process. PMID- 25126214 TI - The value of biologics. AB - American Health & Drug BenefitsTM has reached out to a health and drug benefit decision maker to open a dialogue on the benefits coverage implications surrounding the high cost of biologic drugs. We asked Dr. Gary Owens to discuss with us how payors are turning data points, demographic trends, and pharmacologic discoveries into formularies and benefit designs that balance the demands of cost, quality, and access to care. With a decade of experience chairing the Pharmacy & Therapeutics Committee at Independence Blue Cross until 2006 to inform him, Dr. Owens described how benefit design structures are being redesigned to meet these interlocking needs. PMID- 25126215 TI - When novelty is not enough. AB - Neither orderly nor fully rational, the current healthcare environment is a mosaic of providers, products, services, and intermediaries delivering healthcare, regulatory, and other government institutions, and consumers. The information required for informed healthcare decisions for novel pharmaceutical interventions varies appreciably with the audience, the therapeutic area, and the stage of product development. In this environment, the viability of new product introductions can be heavily influenced by perceived value as well as by mechanistic novelty. Correspondingly, research and development activities can be influenced profoundly by the use of incentive-based formularies, prior authorization requirements, or systems of reimbursement that mandate a stream of evidence confirming clinical utility in the presence of therapeutic uncertainty (eg, Centers for Medicare & Medicaid Services, Coverage with Evidence Development). The economic impact of innovative technology on the healthcare system, as well as the effects on the individual patient, can become a significant variable that influences the extent of research activities from the bench to the physician-patient-payor interface. PMID- 25126216 TI - Asthma-The National Surveillance Data and the National Asthma Education and Prevention Program's Expert Panel Report 3. AB - "The disease often begins in childhood and sometimes lasts until old age. It may follow an attack of whooping cough. One of the most striking peculiarities is the bizarre and extraordinary variety of circumstances, which at times induce a paroxysm. Among these local conditions, climate or atmosphere is most important." -William Osler, MD (1905) Asthma was familiar to various Greek and Roman authors; however, the attacks of severe wheezing were confused with dyspnea from other causes.1 By the 1900s many of the key attributes of the disease state were well described, such as spasm of the bronchial muscles, swelling of the bronchial mucous membrane, and the role of inflammation. The disease was recognized to run in families, and to be influenced by provocative stimuli such as odors, flowers, hay, and emanations from animals.2 Today, asthma continues to be recognized as a chronic inflammatory disease of the lungs, which typically presents with intermittent cough, wheezing, shortness of breath or dyspnea, and chest tightness, commonly occurring during the night and early morning. The underlying inflammation leads to airway hyperresponsiveness and obstruction with some degree of reversibility. This inflammatory reaction may result in sudden exacerbations and chronic progressive structural changes within the lung. PMID- 25126218 TI - The great p value: we the people. PMID- 25126217 TI - Behind-the-Counter Drug Access. PMID- 25126219 TI - Health reform in america. PMID- 25126220 TI - Medicare coverage policies for biologics: the broad gray line. AB - In October 2007, American Health & Drug Benefits asked Dr Joseph Antos to discuss the forces that have shaped Medicare's policies and their impact on the various stakeholders in US healthcare. The first part of the interview appeared in AHDB in February 2008. This second part focuses on the impact of the Centers for Medicare & Medicaid Services drug coverage on the future of biologic products. This discussion does not reflect any new developments occurring after October, such as the recent recommendation of the US Food and Drug Administration advisory committee to narrow the indication for erythropoiesis-stimulating agents to patients with cancer. PMID- 25126221 TI - Benchmarking new frontiers in managed care pharmacy. AB - In 2006, the Foundation for Managed Care Pharmacy-a nonprofit charitable trust affiliated with the Academy of Managed Care Pharmacy-sponsored a survey that was conducted by The HSM Group, a national healthcare market research and consulting firm, and supported by an unrestricted grant from Merck & Co. The survey was repeated in 2007 and was designed to track the evolution of new healthcare trends, gauge the role of managed care pharmacy experts in these trends and the initiatives evolving from them, and disseminate that information to the various stakeholders of the industry. The authors examine the responses of 186 respondents from 71 national health plans, 54 pharmacy benefit management companies, as well as several hospitals, health systems, physician groups, or pharmacies. Survey findings highlight emerging trends in healthcare today and provide insight into the role of managed care pharmacy experts in today's healthcare environment, as well as other variables that may affect the future of the US healthcare delivery system. PMID- 25126222 TI - Not Waiting for Godot: The Evolution of Health Promotion at PPG Industries. AB - PPG Industries is a manufacturer of coatings, chemicals, optical products, specialty materials, glass, and fiberglass. The company's approach to healthcare combines perhaps 2 disparate concepts. The first is that employee health and behavior change relies to a large degree on employee awareness and ownership of their own health and second that "what gets measured gets done." It is widely acknowledged that one of the best tools for employee awareness is the health risk appraisal tool. Additional components of employee awareness include knowing key individual health metrics and effectively engaging with healthcare providers. As a leading global manufacturer, PPG well understands the critical importance of cost accounting and financial metrics to drive business decisions. PPG's perhaps unique approach comes from the strong marriage of individual health/wellness promotion and frequent, timely, and informative financial metrics on health and the cost of care. Combining capacity building through the mobilization of volunteer wellness teams with expert interventions and financial discipline is a feature of the experience here described. This approach has resulted in both management and employee engagement in the issue and has allowed PPG to bend the curve of ever-increasing healthcare costs and achieve cost increases per employee at one half the reported national average for companies of comparable size. Because this journal is dedicated to health and drug benefits, we gathered an appropriately representative team composed of a physician, an epidemiologist who resides in a pharmacy school, and a benefits manager. The team evolved from a common vision to identify ways of improving employee health and well-being. The team presented both as keynote speakers and as contributors to a breakout session at the National Symposium on Work-Life organized in 2007 by the National Institute for Occupational Safety and Health, a federal agency of the Centers for Disease Control and Prevention in the Department of Health and Human Services. This article is an account of why and how such a unique team was formed. PMID- 25126223 TI - Meta-analysis 101: what you want to know in the era of comparative effectiveness. AB - In the era of "comparative effectiveness" research, each of the major stakeholders in healthcare-payors, patients, providers, and government-face a similar challenge. When making a decision about whether a new device, drug, or a diagnostic modality should be considered for use or coverage, what choices are best supported by the evidence? Medical evidence is defined by randomized controlled trials and by observational studies that vary greatly in their design, the accuracy of their analyses, and the relevance of their conclusions and recommendations. Hence, key decision makers increasingly rely on systematic reviews and meta-analyses to facilitate the interpretation and application of research evidence. Knowing how to evaluate meta-analyses and understanding the potential pitfalls of the method are crucial for those involved in designing drug benefits. The authors highlight the process, strengths, and weaknesses of meta analysis and explain how to judge the value of the results. PMID- 25126224 TI - Depression overview. AB - Depression is a common condition that often remains undiagnosed and untreated; however, symptoms are more likely to be recognized today than in past decades. Survey data suggest that female, nonwhite patients are more likely to report depressive symptoms, especially those who are less educated, poor, and covered by Medicaid. Depression may be a finding suggestive of dysthymic disorder, minor or major depressive disorder, seasonal affective disorder, episodic depression, or a sign of an associated mood disorder, such as bipolar disorder. Many effective treatments are available that are well tolerated. This article outlines the diagnostic approach used in primary care, as well as the different treatment options available for this condition. Depression can have serious consequences and must be treated appropriately. PMID- 25126225 TI - Seizing the opportunity. PMID- 25126227 TI - Avoiding the unthinkable: a tale of 2 triangles and the process of care they govern. PMID- 25126226 TI - Regulatory concerns fuel hunger in congress for FDA reform. PMID- 25126228 TI - The unbearable lightness of mental health. PMID- 25126230 TI - Managed care and medicare use of generics: seizing the opportunity, part 2. PMID- 25126229 TI - Schizophrenia: current concepts and approaches to patient care. AB - Schizophrenia is the most serious of all mental conditions. It is typically a long-lasting condition characterized by repeated relapses and by marked functional impairment. Genetic and environmental factors are important. Exactly which factors and how these combine to cause schizophrenia is still unclear. Antipsychotic medications form the bedrock for treatment. These drugs are effective, but not entirely so, and are associated with negative side effects. Individual differences among the available medications suggest that trials with a different medication may be appropriate when one agent fails or is not appropriate for the specific patient. Monitoring for side effects is important to ensure efficacy and compliance. Often, patients choose to stop taking their medications for a variety of reasons, which invariably will lead most patients to a relapse of illness. Beyond medications, patients need considerable support and specialized services. Families are a key resource. The recent focus on personal determination has led to recovery-based services, including the incorporation of peer support into patient care. PMID- 25126231 TI - Trends in pharmaceutical expenditures: the impact on drug benefit design. AB - Annual national spending for pharmaceutical agents was increasing at a rapid pace during the late 1990s and early part of the 21st century, outpacing increases in spending on hospital care and on physician services, which had dominated the industry in the 1970s. In the past few years, however, this trend has shifted, resulting in a lower growth rate in 2005. The reasons for these trends of increases and subsequent declines are explained in this article, including the slower pace of increase in generics and the increasing role of biologic agents in the rate of pharmaceutical price inflation. The sharp increases in drug spending led to changes in prescription drug benefit designs that have not been fully tested. The recent decline creates an opportunity for health plans to evaluate the value of current and new strategies and implement value-based benefit designs in accordance with the shifting focus in healthcare toward value-based patient care. PMID- 25126233 TI - What is happening to the pipeline? PMID- 25126232 TI - Medicare coverage for erythropoiesis-stimulating agents: the perfect storm. AB - Medicare policy changes have an immediate impact on health plans with regard to setting payment policy for providers. So when Medicare tightened payment guidelines for a lucrative class of anemia drugs-erythropoiesis-stimulating agents-an ambitious set of rules was put into effect. Health plans often follow suit in short order, enforcing public guidelines on private payors, even when saving money is not a consideration. However, when Medicare takes an unreasonably hard line, plans tend to focus on members and physicians more fervently, attempting to soften the hard line. In this first part of the interview, Dr Silver examines the coverage decisions set by the Centers for Medicare & Medicaid Services for the use of erythropoiesis-stimulating agents and discusses the issues surrounding their adoption, indications versus off-label use, as well as lingering questions about their role in tumor progression and other risk factors. PMID- 25126234 TI - Results-driven Healthcare: Addressing the Staggering Cost of Poor Performance. PMID- 25126235 TI - Comparing pharmacy benefit managers: moving well beyond the simple spreadsheet analysis. AB - Unabated increases in prescription drug demands, advancing technology, and rising drug inflation rates combined with a sagging economy, continue to intensify budget pressures for payors responsible for delivering pharmacy benefits to plan members. At the same time, high levels of complexity and resource requirements in drug benefit administration have led to a state in which plan sponsors remain heavily dependent on pharmacy benefit managers to assist in these efforts. With pharmacy representing such a critical component of healthcare delivery from clinical and economic perspectives, it is essential that sponsors exercise high levels of due diligence in pharmacy benefit manager review and appraisal to ensure proper balance of quality clinical care, sufficient access, and optimal cost-efficiency in the delivery of such benefits. This review is designed to provide a comprehensive understanding of current pharmacy benefit management business practices and help equip plan sponsors with the knowledge, strategies, and safeguards to drive a well-informed pharmacy benefit selection process and, inevitably, a better-aligned pharmacy benefit management-payor relationship. PMID- 25126236 TI - Where generics and biologics meet. PMID- 25126237 TI - Capnography monitoring enhances safety of postoperative patient-controlled analgesia. AB - BACKGROUND: Patient-controlled analgesia is associated with potentially fatal opioid-related respiratory depression. Opioids are a well-recognized cause of respiratory depression. However, in the postoperative patient, unrecognized pulmonary disease may lead to retention of carbon dioxide, which is further antagonized by opioids and may lead to life-threatening respiratory depression. Therefore, using a method that would provide earlier warnings for respiratory problems could improve patient outcomes. OBJECTIVE: To assess the efficacy of monitoring postoperative patients who were receiving patient-controlled opioid therapy with capnography modules in addition to the routine use of pulse oximetry to monitor ventilatory status and generate alerts when respiratory parameters exceed hospital-established limits. METHOD: Postoperative patients receiving patient-controlled analgesia were compared in relation to the use of pulse oximetry and capnography modules and their ability to generate alerts about abnormal respiratory parameters. A total of 634 patients receiving patient controlled analgesia therapy were studied, of whom 239 (38%) received hydromorphone, 297 (47%) received morphine, and 98 (15%) received fentanyl. All 9 patients experiencing respiratory depression received supplemental oxygen. RESULTS: Of the 634 patients studied, 9 (1.4%) experienced respiratory depression by bradypnea (<6 breaths per minute). Six (67%) events were related to hydromorphone and 3 (33%) were related to morphine. In 7 (78%) events, there was no basal infusion rate and the saturation of peripheral oxygen was >92%. All respiratory depression events occurred within the first 24 hours of patient controlled analgesia therapy. In all cases, capnography, but not pulse oximetry, alerted the nurse to impending respiratory depression. CONCLUSIONS: Capnography was more effective than pulse oximetry in providing early warning of respiratory depression in patients receiving supplemental oxygen. Capnographic monitoring and automatic pausing of patient-controlled analgesia improved postoperative outcomes in situations that could have otherwise been fatal. Use of capnography improved clinician confidence that opioid dosing could be safely continued in postoperative patients for more effective pain management. PMID- 25126238 TI - The NCCN Compendium for Cancer Management. AB - Early in 2008, American Health & Drug Benefits asked Dr Bill McGivney to discuss the National Comprehensive Cancer Network Drugs and Biologics Compendium and guidelines, which represent the evaluation of current evidence on cancer management and the integration of expert judgment in a consensus fashion by oncologists from National Comprehensive Cancer Network institutions. Several advantages that may explain the increasing popularity and acceptance of the Compendium and the guidelines are the authoritative nature of the National Comprehensive Cancer Network experts, the rapid updates, and the free online access. The Centers for Medicare & Medicaid Services reference the guidelines specifically on coverage questions related to oncology and is currently evaluating whether to recognize the Compendium as a basis for Medicare coverage decisions for cancer patients. A decision is expected in June 2008. In January 2008, UnitedHealthcare announced that it would be using the Compendium as a basis for their coverage decisions for patients with cancer, a fact that may influence other private health insurance companies to follow suit. In this interview, Dr McGivney discusses some of the unique features of the guidelines and the Compendium and what differentiates them from available guidelines and compendia of other cancer organizations, including the American Society of Clinical Oncology. PMID- 25126239 TI - Contracting for compliance: using adherence as a patient-centered measure of performance. PMID- 25126241 TI - FDA bolsters its generic approval process: health plans reap the benefits. PMID- 25126240 TI - Wayward prescriptions: costs of fraud in payor plans. AB - The cost of prescription drugs and medical devices has increased dramatically over the past several years. This increase has exceeded the annual average inflation index, making medical products desired sources of ill-gotten financial gains through diversion, theft, fraud, and deceit. With databases often being compromised, personal health information, personal identification, and therapy history are all available to be used by thieves through deception and misrepresentation, and are being traded on clandestine websites. With increasing values of medical services, wanted efforts continue to emerge in profiteering schemes, using illicit deals for financial gains by exploiting what was once perceived as sacred areas of medical care. Estimates of healthcare resource costs in dollars, lives, and products exceed $200 billion. Select examples of fraud in our medical services are presented that expose plan members to the risks of loss and theft that can compromise the privacy of their health records. The author outlines prevention steps for payors to guard against such practices. PMID- 25126242 TI - Heparin at the center of the storm. PMID- 25126243 TI - Prescribing warfarin appropriately to meet patient safety goals. AB - The anticoagulant warfarin is increasingly used in a variety of disorders associated with risk of thromboembolism. The drug is undoubtedly effective but is linked to numerous nutrient, disease, and drug interactions; safe use of warfarin therefore necessitates close patient monitoring, using the international normalized ratio. The predominant adverse effect is bleeding, and individuals respond to warfarin in different ways. Both high and subtherapeutic international normalized ratios warrant attention, whereas a high international normalized ratio, with or without bleeding, mandates prompt patient evaluation. The 2008 National Patient Safety Goals require medical institutions to develop processes to ensure the safe use and monitoring of anticoagulant use. Last August, the US Food and Drug Administration revised the prescribing information for warfarin to include genetic testing before initiating therapy, although this is still not covered by most health plans. PMID- 25126245 TI - The international society for pharmacoeconomics and outcomes research: implications for decision makers in healthcare. PMID- 25126244 TI - Treading water: the no-growth investment in health services research. AB - There is a "perfect storm" brewing in the American healthcare system. Healthcare spending has grown faster than our economy for many years and is projected to double in as little as 10 years. In spite of what we spend on healthcare, research tells us that we only receive appropriate care half the time. We are simply not getting what we are paying for. Health services research provides the data and the evidence needed to make better decisions, design healthcare benefits, and develop effective policies to optimize healthcare financing, facilitate access to healthcare services, and improve healthcare outcomes. Despite what we know and what we can learn from health services research, federal funding for this important field continues to erode. This article provides a primer on the federal budget process and summarizes findings from the Federal Funding for Health Services Research 2007. PMID- 25126246 TI - Quality in the pharmacy environment. PMID- 25126247 TI - Delaware's Wellness Program: Motivating Employees Improves Health and Saves Money. AB - BACKGROUND: Every year, employers around the country evaluate their company benefits package in the hopes of finding a solution to the ever-rising cost of health insurance premiums. For many business executives, the only logical choice is to pass along those costs to the employee. OBJECTIVES: As an employer, our goal in Delaware has always been to come up with innovative solutions to drive down the cost of health insurance premiums while encouraging our employees to take responsibility for their own health and wellness by living a healthy and active lifestyle, and provide them with the necessary tools. METHODS: The DelaWELL program (N = 68,000) was launched in 2007, after being tested in initial (N = 100) and expanded (N = 1500) pilot programs from 2004 to 2006 in which 3 similar groups were compared before and after the pilot. Employee health risk assessment, education, and incentives provided employees the necessary tools we had assumed would help them make healthier lifestyle choices. RESULTS: In the first pilot, fewer emergency department visits and lower blood pressure levels resulted in direct savings of more than $62,000. In the expanded pilot, in all 3 groups blood pressure was significantly reduced (P <.001) from preprogram to postprogram; body fat reduction was also significant (P <.001); and glucose levels dropped (P <.001) in 2 groups. The overall saving was about $450,000. And in only about 4 months this year, 729 employees participating in DelaWELL had a combined weight loss of 5162 lb. CONCLUSIONS: Decision makers in the State of Delaware have come up with an innovative solution to controlling costs while offering employees an attractive benefits package. The savings from its employee benefit program have allowed the state to pass along the savings to employees by maintaining employee-paid health insurance contributions at the same level for the past 3 years. DelaWELL has already confirmed our motto, "Although it may seem an unusual business investment to pay for healthcare before the need arises, in Delaware we concluded that this makes perfect sense." This promising approach to improving health and reducing healthcare costs could potentially be applied to other employer groups. PMID- 25126248 TI - Switching to generic antiepileptic drugs: growing concerns. PMID- 25126249 TI - The better quality information to improve care for medicare beneficiaries project: exploring approaches to physician performance measurement. AB - On August 22, 2006, President Bush issued an Executive Order calling on all federal agencies and those who do healthcare business with the government to engage in collaborative efforts to incorporate the 4 cornerstones of value-driven healthcare: health information technology standards, quality standards, price standards, and incentives. The Department of Health and Human Services has embarked on a campaign to make these 4 cornerstones a reality by encouraging the public and private sectors to work collaboratively at the local level. In support of this campaign, the Centers for Medicare & Medicaid Services launched a project in late 2006 that leverages local collaboratives as a means to explore a national approach to physician performance measurement. This project, which is known as the Better Quality Information to Improve Care for Medicare Beneficiaries Project, aims to test methods to aggregate Medicare administrative data with data from commercial health plans and, in some cases, Medicaid, in 6 local collaboratives to calculate and report quality measures for physician groups and for some individual physicians. PMID- 25126251 TI - Potayto-Potahto? The Meaning of the FDA's "Complete Response" Letters. PMID- 25126250 TI - Emerging trends in outsourcing healthcare: medical tourism. PMID- 25126253 TI - e-Prescribing: Stakeholders Collaborating to Reduce Medication Errors. PMID- 25126252 TI - Chronic obstructive pulmonary disease: an overview. AB - Chronic obstructive pulmonary disease is a growing healthcare problem that is expected to worsen as the population ages and the worldwide use of tobacco products increases. Smoking cessation is the only effective means of prevention. Employers are in a unique position to help employees stop smoking. During the long asymptomatic phase, lung function nevertheless continues to decline; therefore, many patients seek medical attention only when they are at an advanced stage or when they have experienced an acute exacerbation. To help preserve patients' quality of life and reduce healthcare costs related to this chronic disease, clinicians need to accurately diagnose the condition and appropriately manage patients through the long course of their illness. This article discusses the current approach to patient management. PMID- 25126254 TI - Cutting through the politics: presidential candidates' healthcare platforms and impact on health benefits. AB - Healthcare reform is one of the top issues for the presidential elections this year, and both candidates have proposed a wide range of health policy changes that could be the most important changes to the delivery of care in the country since the creation of Medicare and Medicaid in the 1960s. This article provides a summary analysis of the healthcare platforms of the presidential candidates. Specifically, the major components of their published health plan proposals are broken out and compared using the language and descriptions from the candidates. The article also highlights several healthcare reform proposals from health advocacy organizations, as well as insights from medical directors and pharmacy directors across more than 50 major managed care health plans. By framing the issues, the article provides a basis for consideration of more detail as healthcare reform recommendations are developed by Congress in 2009. PMID- 25126255 TI - Medication therapy management goes hi-tech: implementing automated software improves pharmacy efficiency. AB - BACKGROUND: With the Centers for Medicare & Medicaid Services mandate that all Medicare Part D benefit sponsors must offer members a medication therapy management program, pharmacists were facing new challenges of data collecting using software applications that had limited use for the new program. OBJECTIVE: Health Net pharmacists initiated an automated software application to increase the efficiency of the medication therapy management program, the integrity of the member profiles, and the ability to provide accurate reporting of drug-related issues. METHODS: Pharmacists were integral contributors to the automated software program; they developed the clinical algorithms, screen layout and transitions, and program functionality. Together with a programming company-Cognizant Technology Solutions-they created a web-based software application to accommodate an increasing number of eligible members and ensure accuracy of the information; they also performed testing of the final product. RESULTS: The new program includes member demographics and qualifying parameters that are uploaded monthly. All drug-related problems are now displayed and updated automatically by the software application. Assessment questions are answered and saved within the software, and reporting functions allow for quick and accurate results. Consequently, the number of drug regimen reviews and drug problems identified has increased by more than 300%. CONCLUSION: The automated software application is capable of maintaining and updating medication claims, sending and receiving faxes to physicians and pharmacies, and allows for documentation of patient specific freeform text. Each profile is extensive and allows the pharmacist to get all necessary information from a single source. PMID- 25126256 TI - Presidential candidates strong supporters of greater access to generics and biosimilars. PMID- 25126258 TI - New reporting system for potential safety concerns of drugs on the market. PMID- 25126257 TI - Cost-effectiveness of second-generation antihistamines and montelukast in relieving allergic rhinitis nasal symptoms. AB - OBJECTIVE: Allergic rhinitis imposes a significant health and economic burden both on individuals and the healthcare system. Second-generation prescription antihistamines, levocetirizine, fexofenadine, and desloratadine, and the leukotriene receptor antagonist, montelukast, differ in their ability to relieve common rhinitis symptoms. The purpose of this study was to compare the cost effectiveness of prescription agents based on their effectiveness in relieving nasal symptoms. METHODS: Effectiveness was measured as the composite of nasal symptoms, including congestion, rhinorrhea, and sneezing, from clinical studies that compared each of the 4 comparators to placebo. Direct costs included prescription therapy and rhinitis-related physician office visits. Physician office visit costs were collected from an analysis of the PharMetrics insurance claims database. Sensitivity analyses were conducted using a Monte Carlo simulation to assess the robustness of the average and incremental cost effectiveness ratios. RESULTS: The cost per clinically significant improvement of nasal symptoms for levocetirizine was less than for the other model comparator agents. The incremental cost-effectiveness ratio for levocetirizine dominated montelukast and desloratadine and was lower than either branded or generic fexofenadine. CONCLUSION: Levocetirizine is a cost-effective therapy for the relief of nasal symptoms of allergic rhinitis. PMID- 25126260 TI - e-Prescribing: A Move Toward Appropriate Medication Use. PMID- 25126259 TI - Evaluation and management of diabetes mellitus. AB - Diabetes mellitus is a major public health problem with tremendous medical and economic burdens. It is the seventh leading cause of death and the number one cause of end-stage renal disease, adult blindness, impotence, and nontraumatic lower-limb amputation in the United States. People with diabetes are 2 to 4 times more likely to suffer from stroke or from cardiovascular disease, and are twice as likely to die compared with age-matched individuals without diabetes. Diabetes cost the United States around $174 billion in 2007, $58 billion of which was related to disability, work loss, and early mortality. Although there is currently no known cure for diabetes, much progress has been made over the past 2 decades to improve the diagnosis and management of diabetes. Evidence has shown that applying aggressive interventions early can prevent or delay progression to microvascular complications that increase the mortality rate in diabetes. The authors review the guidelines for optimal evaluation of diabetes mellitus and discuss the current and emerging therapeutic options available in the United States. PMID- 25126261 TI - Focus on lowest net cost drug reduces costs for patients, plan sponsors. PMID- 25126262 TI - Erythropoiesis-stimulating agents in a meta-stable state: guidelines, economics, and policy in flux. AB - Medicare coverage of erythropoiesis-stimulating agents is a complex issue with implications for a variety of healthcare stakeholders. In the first part of the interview (see AHDB, May 2008), Samuel M. Silver, MD, PhD, examined the evolution and clinical implications of the Medicare coverage decisions and the eventual shift in clinical practice away from the approved indication to situations involving quality-of-life issues. In this second part, Dr Silver discusses with F. Randy Vogenberg, RPh, PhD, the clinical implications of the Medicare coverage decision regarding erythropoiesis-stimulating agents, pointing out the noneconomic reasons why transfusions can be risky to cancer patients, and how such policy decisions can have profound implications for patients. Dr Silver calls for new studies to be Initiated, which would be funded by the 2 major manufacturers of these drugs, to investigate the concerns regarding tumor progression and thromboembolic events that are potentially associated with these expensive and potentially toxic medications. The discussion resumes where Dr Silver explains why it would be good to compare claims data of cancer patients who are receiving these medications and their transfusion requirements. PMID- 25126263 TI - Role for automated communication strategies in medication adherence management. AB - Lack of medication adherence is a prevalent problem that causes a broad range of health-and health-economics-related issues. Adherence management is therefore an important strategy, but it also presents its own set of challenges. Interventional communication from care support teams at managed care organizations and disease management and wellness programs has proved effective at modifying patients' medication adherence and reporting behaviors. However, these communications do not work well from an economic standpoint. It is not economically feasible to scale call centers and the numbers of clinical and professional staff to communicate with the increasing number of patients with chronic diseases who require ongoing medication use. Using communication automation to augment traditional call center outreach can help to mediate patient medication-taking behaviors. Specific design criteria for the automation of this interaction are discussed in this article, offering supporting data from a recent trial of 304 elderly patients with hypertension, and showing the benefits of using such a system for effective blood pressure monitoring, at reduced costs. PMID- 25126264 TI - An overview of cholesterol management. AB - Cardiovascular disease is the leading cause of death worldwide. Elevated cholesterol (hypercholesterolemia) and abnormal lipid profiles (dyslipidemia) are important risk factors for the development of cardiovascular disease. This article discusses the role of cholesterol in the body and the relationship between different cholesterol fractions and the risk of cardiovascular disease. The guidelines for assessment and treatment of dyslipidemia from the National Cholesterol Education Program are outlined, and cholesterol targets and goals of therapy are discussed. The mechanism of action, place in therapy (eg, first-line, second-line, or add-on), and common side effects are also discussed for each of the available classes of drugs used in the treatment of dyslipidemia. PMID- 25126266 TI - Healthcare innovation viability: on the edge of a knife. PMID- 25126265 TI - Promotion of medical tourism in the media creates a trend. PMID- 25126267 TI - Why Financial Incentives Aren't Enough to Move the Needle on Compliance. PMID- 25126269 TI - Recent slowdown in national health expenditures attributed to growing use of generics. PMID- 25126268 TI - Prescription copay reduction program for diabetic employees: impact on medication compliance and healthcare costs and utilization. AB - OBJECTIVE: To examine the impact of a value-based benefit design on utilization and expenditures. METHODS: This benefit design involved all diabetes-related drugs and testing supplies placed on the lowest copay tier for 1 employer group. The sample of diabetic members were enrolled from a 9-month preperiod and for 2 years after the benefit design was implemented. Measured outcomes included prescription drug utilization for diabetes and medical utilization. Generalized measures were used to estimate differences between years 1 and 2 and the preperiod adjusting for age, gender, and comorbidity risk. RESULTS: Diabetes prescription drug use increased by 9.5% in year 1 and by 5.5% in year 2, and mean adherence increased by 7% to 8% in year 1 and fell slightly in year 2 compared with the preperiod. Pharmacy expenditures increased by 47% and 53% and expenditures for diabetes services increased by 16% and 32% in years 1 and 2, respectively. CONCLUSION: Increases in adherence and use of diabetes medications were observed. There were no compensatory cost-savings for the employer through lower utilization of medical expenditures in the first 2 years. Adherent patients had fewer emergency department visits than nonadherent patients after the implementation of this benefit design. PMID- 25126270 TI - Partial compliance with antipsychotics increases mental health hospitalizations in schizophrenic patients: analysis of a national managed care database. AB - OBJECTIVE: To investigate the relationship between partial compliance with antipsychotic medication and mental health hospitalization in managed care patients with schizophrenia. STUDY DESIGN: We performed a retrospective evaluation of 1499 outpatients with >=1 antipsychotic claims and a diagnosis of schizophrenia in a managed care database (PHARMetrics). METHODS: Patients were followed for 12 months after their initial oral antipsychotic prescribing event. Compliance was estimated by gaps in medication therapy, medication consistency and persistence, and medication possession ratio. Categorical and logistic regression analyses modeled effects of compliance, age, and gender on hospitalization risk. RESULTS: The managed care cohort had an overall hospitalization risk of 5.9% during follow-up. Increased hospitalization risk was associated with lower partial compliance, as measured by 3 of the 4 definitions. Patients with a maximum gap of >30 days were 4.7 times more likely to be hospitalized than those with a maximum gap of 0 to 10 days (P <.001). Low medication consistency of <70% and a medication possession ratio of <70% were significantly associated with increased risk of hospitalization (P <.001). Logistic regression analyses indicated that hospitalization odds decreased 16.9% (P <.001) and 18.8% (P <.001) for every 10% increase in medication possession ratio and medication consistency, respectively. CONCLUSION: Small decreases in compliance with antipsychotics are associated with increased hospitalization risk among patients with schizophrenia in a managed care population. PMID- 25126272 TI - What changes can your health plan expect from the new administration? AB - The new administration has already begun to introduce changes in some areas of government. To outline potential key changes to the US healthcare system and their impact on health plans, Robert Henry and Kip Piper of AHDB asked Dan Mendelson to draw on his experience as current president and founder of Avalere Health, as well as on his previous role as Associate Director for Health at the White House's Office of Management and Budget during the Clinton Administration. Mr Mendelson focuses on what he sees as key changes that will have direct implications for decision makers in healthcare, including (1) a greater emphasis on plan beneficiaries' protection, and (2) increased regulatory focus on plan operations. Plans can expect to have less government trust in actuarial submissions and probably more oversight and supervision of the daily operation of a plan. The triangle of quality, access, and cost will likely reflect the point of view of the beneficiary rather than that of plan administrators. Other topics discussed include the potential benefits of postmarketing surveillance, new opportunities for expediting drug approvals, and the new and increasing emphasis on comparative effectiveness research and health information technology. PMID- 25126271 TI - Alzheimer's disease: a healthcare burden of epidemic proportion. AB - Alzheimer's disease is the most common cause of dementia and increases in prevalence exponentially with age, with trends in the United States likely to worsen in ensuing decades. The pathology in Alzheimer's disease is characterized by an increase in extracellular amyloid plaques and intraneural neurofibrillary tangles, with neuronal destruction in several areas of the brain, and biochemically by a deficiency in acetylcholine; clinical manifestations include progressive loss of memory, change in personality, and behavioral disturbances. Pharmacotherapy includes the T.S. Dharmarajan Srinivas G. Gunturu use of cholinesterase inhibitors and memantine; addressing the many behavioral manifestations of the disease, especially in advanced stages, imposes tremendous burden to caregivers and healthcare resources. PMID- 25126273 TI - Patient cost-sharing on the rise: results from the benefit design index. AB - OBJECTIVE: The relationship between healthcare insurers and employers plays a critical role today in decisions about benefit design, cost-sharing, and even the coverage of individual products and services. To better understand how these 2 stakeholders interact in the creation of healthcare benefit design, the Zitter Group conducted a large national study of insurer-employer relationship. METHODS: This study is based on a primary web-based survey with 100 top decision makers in large national and important regional commercial managed care plans, and a similar survey of 100 employers and employer benefit consultants, including medical directors and benefit decision makers. This article reviews the results of this research, especially in relation to insurer and employer opinions on patient cost-sharing. RESULTS: Findings from this study show that cost-shifting remains the prevailing cost-containment strategy used by insurers and employers. These stakeholders expect that additional cost-shifting will have minimal impact on patient health outcomes. CONCLUSION: Despite accumulating evidence that cost shifting leads to undesirable health and cost consequences and has largely failed to slow health cost growth, employers and insurers will likely continue to rely on this modality as their primary cost-containment strategy. PMID- 25126274 TI - Will 2009 usher in the era of biogenerics? PMID- 25126275 TI - Employer-based health initiative: impact on employees' cardiovascular outcomes. AB - BACKGROUND: Cardiovascular disease is the primary cause of mortality among men and women in the United States. The Ready, Set, Goal program was an employer based initiative designed to identify individuals at risk for cardiovascular disease and to offer an intervention to alter those risk factors. The program involved cardiovascular education, screening, behavior-change incentives, continuing assessment, and follow-up. Pharmacologic treatment was not part of the intervention. OBJECTIVE: To analyze the effects of the Ready, Set, Goal pilot program in 5 employers in the United States on salient cardiovascular end points for employees who completed the program. METHODS: The analysis used a pretest/posttest within-subjects design to compare baseline measurements with measurements for all subjects who completed a second assessment 6 months after baseline measurements. Enrollment began in June 2004 in the first site and in May 2005 in the last site; it ended in January 2006. Patient clinical data from the pilot interventions were aggregated to assess the effects of the intervention on salient cardiovascular end points for individuals who completed the Ready, Set, Goal program. Changes in short-term cardiovascular risk factors were evaluated. Descriptive measures with paired t-tests (alpha = 0.05) were calculated at the aggregate level for each dependent variable. Range checks were conducted on all variables for clinical validity. RESULTS: A total of 589 subjects from 5 employer group pilot interventions completed the program. Of these, 43% were men, 60% were white, 9% were African-American, 11% were Hispanic, and 20% were categorized as "other." After the intervention, mean blood pressure, total cholesterol, and low density lipoprotein cholesterol levels were significantly lower (P <.05) compared with baseline measurements. On average, systolic blood pressure declined by 1.9 mm Hg; diastolic blood pressure by 1.3 mm Hg; total cholesterol decreased by 5.2 mg/dL and low-density lipoprotein cholesterol by 3.4 mg/dL. Triglyceride levels increased and high-density lipoprotein levels decreased, although these changes were not significant, and neither were the mean increases in body weight. But increases in body mass index were significant. CONCLUSIONS: A worksite cardiovascular health program can have positive effects on salient cardiovascular end points for employees. The increases in triglyceridnes and body mass index should be further explored. PMID- 25126277 TI - The paradox of public policy reform: change or continuum? PMID- 25126278 TI - Are you kidding me? Clinical comparative effectiveness or evidence-based medicine. PMID- 25126276 TI - Methicillin-Resistant Staphylococcus aureus: A Growing Risk in the Hospital and in the Community. AB - Methicillin-resistant Staphylococcus aureus is a common and continuously growing cause of nosocomial and community-acquired infections. The type, disease severity, and clinical outcomes of these infections, as well as the genotypic and susceptibility patterns of the bacteria differ according to the setting in which the infection occurs-a healthcare facility or the community setting. The incidence of these infections in the community setting has been growing consistently in the past decade or so. In addition, resistance to the many current antibiotics used to treat these infections is also growing, further complicating management. Rapid-diagnosis tests and new therapeutic agents are constantly under investigation. The authors review the current understanding of the epidemiology, clinical manifestations, and management of methicillin resistant Staphylococcus aureus infection, including the growing problem of resistance. In addition, they discuss promising diagnostic and therapeutic alternatives, as well as new control strategies to prevent its transmission or the development of infection among carriers. PMID- 25126280 TI - New legislations on generics and biosimilars brewing in congress. PMID- 25126279 TI - MIPPA: First Broad Changes to Medicare Part D Plan Operations. AB - In July 2008, as part of broad Medicare reform, Congress passed the first major legislative changes to Medicare Part D since its enactment in 2003-the Medicare Improvements for Patients and Providers Act. This new legislation has significant implications for how Part D plans can market and enroll Medicare beneficiaries. The new legislation also strengthened beneficiary protections, expanded the low income subsidy provisions originally included in Part D, and expanded Part D coverage. These changes have significant implications for the operation of Part D plans and can affect those involved in benefit design, including specialty pharmacy coverage. This article discusses the major changes that took effect on January 1, 2009, and have immediate implications for Part D plan sponsors, including Medicare Advantage plans and stand-alone prescription drug plans. PMID- 25126281 TI - ProvenCare: Geisinger's Model for Care Transformation through Innovative Clinical Initiatives and Value Creation. AB - Geisinger's system of care can be seen as a microcosm of the national delivery of healthcare, with implications for decision makers in other health plans. In this interview, Dr Ronald A. Paulus focuses on Geisinger's unique approach to patient care. In its core, this approach represents a system of quality and value initiatives based on 3 major programs-Proven Health Navigation (medical home); the ProvenCare model; and transitions of care. The goal of such an approach is to optimize disease management by using a rational reimbursement paradigm for appropriate interventions, providing innovative incentives, and engaging patients in their own care as part of any intervention. Dr Paulus explains the reasons why, unlike Geisinger, other stakeholders, including payers, providers, patients, and employers, have no intrinsic reasons to be concerned with quality and value initiatives. In addition, he says, an electronic infrastructure that could be modified as management paradigms evolve is a necessary tool to ensure the healthcare delivery system's ability to adapt to new clinical realities quickly to ensure the continuation of delivering best value for all stakeholders. PMID- 25126282 TI - The integrated patient-centered medical home: tools for transforming our healthcare delivery system. PMID- 25126284 TI - Prioritizing healthcare resources to keep the baby boomers out of nursing homes. PMID- 25126283 TI - Increased Patient Cost-Sharing, Weak US Economy, and Poor Health Habits: Implications for Employers and Insurers. AB - Many healthcare stakeholders, including insurers and employers, agree that growth in healthcare costs is inevitable. But the current trend toward further cost shifting to employees and other health plan members is unsustainable. In 2008, the Zitter Group conducted a large national study on the relationship between insurers and employers, to understand how these 2 healthcare stakeholders interact in the creation of health benefit design. The survey results were previously summarized and discussed in the February/March 2009 issue of this journal. The present article aims to assess the implications of those results in the context of the growing tendency to increase patient cost-sharing, a weak US economy, and poor health habits. Increasing cost-sharing is a blunt instrument: although it may reduce utilization of frivolous services, it may also result in individuals forgoing medically necessary care. Increases in deductibles will lead to an overall decrease in optimal care-seeking behavior as families juggle healthcare costs with a weak economy and stagnating wages. PMID- 25126285 TI - The view from washington: healthcare reform. PMID- 25126286 TI - Applying Evidence for Medical Technologies: Closing the Gap between R&D and Decision Maker Needs. AB - In this interview, Dr Sean Tunis, former Director of the Office of Clinical Standards and Quality and Chief Medical Officer at the Centers for Medicare & Medicaid Services, and current Director of the Center for Medical Technology Policy, discusses the need to align the demands of the industry on product development with provider and patient needs to ensure that products in the pipeline, especially those for chronic disease care, can actually provide clinical benefit. The question is how to make sure that new products and technologies are not only being approved by regulatory bodies but also serve real world needs. This will also promote the acceptance of a product or service by all stakeholders-regulators, providers, payers, and purchasers-while meeting actual patient needs. Another question for payers and employers is how to create a benefit design that encourages the application of evidence in coverage decision making toward value-based healthcare. PMID- 25126287 TI - Biosimilars policy forum: perspectives on safety and efficacy of future products. PMID- 25126288 TI - The working patient with cancer: implications for payers and employers. AB - Cancer is seen today more often as a manageable chronic disease, resulting in changing workplace characteristics of the patient with cancer. A growing number of employees continue to work while being treated for cancer or return to work shortly after their cancer treatment is completed. To respond to these changes and the potential impact on the working patient's attitude, employers need updated, factual information related to this patient population. This type of information will support future benefit considerations by employers on employee contributions and future employee health and productivity. In 2005, Amgen launched a 3-year initiative to better understand cancer as a chronic disease, as well as the impact on the working patient with cancer and on the employer. The data from this initiative described in this article provide insights into cancer as a chronic and manageable disease in the workforce, and the broader implications to payers and employers. PMID- 25126290 TI - Payer perspectives on healthcare reform. PMID- 25126289 TI - Lower copay and oral administration: predictors of first-fill adherence to new asthma prescriptions. AB - BACKGROUND: Nonadherence to asthma medications is associated with increased emergency department visits and hospitalizations. If adherence is to be improved, first-fill adherence is the first goal to meet after the physician and patient have decided to begin treatment. Little is known about first-fill adherence with asthma medications and the factors for no-fill. OBJECTIVE: The goal of the study was to examine the proportion of patients who fill a new prescription for an asthma medication and analyze characteristics associated with this first-fill. METHODS: This retrospective cohort study linked electronic health records with pharmacy claims. The cohort was comprised of 2023 patients aged 18 years or older who sought care from the Geisinger Clinic, had Geisinger Health Plan pharmacy benefits, and were prescribed an asthma medication for the first time between 2002 and 2006. The primary outcome of interest was first-time prescription filled by the patient within 30 days of the prescription order date. Covariates examined included factors related to the patient (ie, age, sex, and ethnicity), comorbidities and utilization (ie, Charlson comorbidity index, number of office visits, number of additional medications), asthma treatment (ie, delivery route, pharmacologic class), and pharmacy copay amount. A logistic-regression model was used to determine covariates associated with first-fill. RESULTS: The overall first-fill rate for new asthma medications was 78%. First-fill rate was lower for patients with a copay above the mean of $12 (odds ratio = 0.76; 95% confidence interval, 0.58-0.99) and higher for patients prescribed oral plus inhaled medications (versus inhaled only, odds ratio = 3.91; 95% confidence interval, 2.15-7.11). CONCLUSIONS: SEVERAL FACTORS ASSOCIATED WITH FAILING TO FILL AN INITIAL PRESCRIPTION FOR ASTHMA CAN BE ADDRESSED THROUGH SIMPLE INTERVENTIONS: screening for difficulties a patient may have in filling prescriptions, avoiding nonformulary medications, and recognizing the barrier that high copays present. In addition, for employers and policymakers, decreasing copay may improve adherence and, therefore, asthma control. PMID- 25126291 TI - Use pattern and off-label use of atypical antipsychotics in bipolar disorder, 1998-2002. AB - BACKGROUND: Postmarketing surveillance that identifies patients at high risk for receiving off-label medications will help ensure that the benefits of such treatment outweigh the risks. Because many off-label uses have little scientific support, tracking the extent to which they occur as well as the particular circumstances under which they occur is important. OBJECTIVE: To describe the drug-use pattern for patients with bipolar disorder, and to identify demographic and clinical factors associated with off-label use of atypical antipsychotics before US Food and Drug Administration approval for this indication. METHODS: Using the PHARMetrics medical claims database, a total of 105,771 adult patients with a diagnosis of bipolar disorder were evaluated during the 5-year (1998-2002) study period. Study drugs included mood stabilizers, antipsychotics, and antidepressants. Off-label use of an atypical antipsychotic was defined as a patient taking olanzapine before March 2000 (when it received an indication for bipolar disorder) or any other atypical antipsychotic during the entire study period. Logistic regression analysis was used to determine the odds ratio of receiving a drug off-label. RESULTS: Utilization of and reimbursement for atypical antipsychotics increased during the 5-year period. Of the 10.5% of patients who took atypical antipsychotics, 7.1% took these drugs off-label. In addition, 11% of patients received lithium, 25% received other anticonvulsants, and 34% received antidepressants. Off-label use of atypical antipsychotics was associated with psychiatry specialist prescribers (odds ratio = 1.52; 95% CI, 1.44-1.59) and certain comorbidities, such as substance abuse (odds ratio = 1.51; 95% CI, 1.38-1.66), anxiety disorder (odds ratio = 1.20; 95% CI, 1.14-1.26), diabetes mellitus (odds ratio = 1.26; 95% CI, 1.16-1.37), cerebral vascular disease (odds ratio = 1.26; 95% CI, 1.10-1.45), and hypertension (odds ratio = 1.12; 95% CI, 1.05-1.20). Over time, there has been an increase in the number of drug therapies, including atypical antipsychotics, used to treat bipolar disorder. CONCLUSION: Because of the significant association found between atypical antipsychotic use and several key comorbidities, it is important for physicians to recognize these associations and weigh the risks and benefits of atypical antipsychotics in their treatment strategies. PMID- 25126292 TI - Predictive and prognostic models: implications for healthcare decision-making in a modern recession. AB - Various modeling tools have been developed to address the lack of standardized processes that incorporate the perspectives of all healthcare stakeholders. Such models can assist in the decision-making process aimed at achieving specific clinical outcomes, as well as guide the allocation of healthcare resources and reduce costs. The current efforts in Congress to change the way healthcare is financed, reimbursed, and delivered have rendered the incorporation of modeling tools into the clinical decision-making all the more important. Prognostic and predictive models are particularly relevant to healthcare, particularly in the clinical decision-making, with implications for payers, patients, and providers. The use of these models is likely to increase, as providers and patients seek to improve their clinical decision process to achieve better outcomes, while reducing overall healthcare costs. PMID- 25126294 TI - Healthcare reform, classicism, and how we treat the elderly: the politics of epidemiology. PMID- 25126293 TI - Estimates of commercial population at high risk for cardiovascular events: impact of aggressive cholesterol reduction. AB - OBJECTIVES: To model the financial and health outcomes impact of intensive statin therapy compared with usual care in a high-risk working-age population (actively employed, commercially insured health plan members and their adult dependents). The target population consists of working-age people who are considered high-risk for cardiovascular disease events because of a history of coronary heart disease. STUDY DESIGN: Three-year event forecast for a sample population generated from the National Health and Nutrition Examination Survey data. METHODS: Using Framingham risk scoring system, the probability of myocardial infarction or stroke events was calculated for a representative sample population, ages 35 to 69 years, of people at high risk for cardiovascular disease, with a history of coronary heart disease. The probability of events for each individual was used to project the number of events expected to be generated for this population. Reductions in cardiovascular and stroke events reported in clinical trials with aggressive statin therapy were applied to these cohorts. We used medical claims data to model the cohorts' event costs. All results are adjusted to reflect the demographics of a typical working-age population. RESULTS: The high-risk cohort (those with coronary heart disease) comprises 4% of the 35- to 69-year-old commercially insured population but generates 22% of the risk for coronary heart disease and stroke. Reduced event rates associated with intensive statin therapy yielded a $58 mean medical cost reduction per treated person per month; a typical payer cost for a 30-day supply of intensive statin therapy is approximately $57. CONCLUSIONS: Aggressive low-density lipoprotein cholesterol-lowering therapy for working-age people at high risk for cardiovascular events and with a history of heart disease appears to have a significant potential to reduce the rate of clinical events and is cost-neutral for payers. PMID- 25126295 TI - Cost-sharing enhances cost control. PMID- 25126296 TI - Can generics help heal our ailing healthcare system? PMID- 25126297 TI - Impact of prescription benefit coverage limits on sevelamer hydrochloride adherence for patients with ESRD. AB - OBJECTIVE: To assess the impact of prescription benefit coverage on medication adherence in Medicare-eligible members diagnosed with end-stage renal disease taking sevelamer hydrochloride. METHODS: This pilot study involved a retrospective analysis of patients with end-stage renal disease taking sevelamer, with an annual cap on brand prescription drug spending compared with those without a cap. We compared sevelamer adherence and discontinuation proportions between the 2 groups of Medicare patients in 2003 and 2004. Medication adherence was calculated based on the proportion of available days covered in relationship to capped versus noncapped pharmacy benefit. RESULTS: Rate ratios showed that in 2003, the patients taking sevelamer under a capped benefit (N = 43) had 27% fewer days of drug use compared with those (N = 88) without a capped benefit (relative risk, 0.73; 95% CI, 0.58-0.93). Similarly, in 2004, those taking sevelamer under the capped benefit (N = 21) had 33% fewer days of drug use compared with those (N = 117) without a capped benefit (relative risk, 0.67; 95% CI, 0.46-0.96). CONCLUSIONS: Medication adherence was significantly lower for patients with a capped brand-name drug benefit. These findings provide insight into potential drug utilization patterns, including for sevelamer, under the Medicare Part D benefit, where members could face significant out-of-pocket expenditures once coverage limits are reached. PMID- 25126298 TI - Private health plans perspectives: electronic personal health records and electronic prescribing. AB - BACKGROUND: Patients, payers, public health researchers, medical economists, and policymakers have all called for aggressive deployment of information technologies to support the management of health records and prescriptions. In response, payers of all types have been making investments in electronic systems. OBJECTIVES: To understand, analyze, and quantify current private payer involvement in electronic personal health records and electronic prescribing development and implementation. METHODS: A web-based survey involving 62 private commercial payer respondents representing more than 80 million covered lives and 16 national plans. RESULTS: Responses showed relatively high rates of implementation of electronic personal health records among respondents (20 currently and 9 in the next 24 months), but a unanimity of agreement of disappointing plan members' utilization of these systems. Implementation rates of electronic prescribing systems are even higher. More than half of the respondents reported utilization rates below 10%. CONCLUSION: The disappointing results with the implementations of electronic systems are most likely the result of variables exogenous to the technologies themselves. The low utilization of electronic prescribing is most likely related to the general lack of penetration of information technology into the work flow of most prescriber offices. PMID- 25126299 TI - Wellness and the governing dynamics of healthcare reform. PMID- 25126300 TI - Health plan retention and pharmacy costs of newly diagnosed patients with chronic kidney disease in a managed care population. AB - BACKGROUND: Chronic kidney disease is prevalent in the United States, and diabetes and hypertension cause up to two thirds of all new cases. Many health plans believe that these patients do not retain their health plans for a long duration, therefore plans do not focus on prevention for this disease. OBJECTIVE: To determine health plan retention rates and direct healthcare costs of adults with newly diagnosed chronic kidney disease with diabetes or hypertension. METHODS: A total of 31,917 patients with chronic kidney disease were included in this study between January 1995 and December 2006, using a managed care database. Patients were divided into 3 subgroups for cost comparison-patients with chronic kidney disease only (n = 8836), those with chronic kidney disease with diabetes (n = 11,252), and patients with chronic kidney disease with hypertension (n = 20,836). Follow-up of patients from index period of initial kidney disease diagnosis was 5 years. Average enrollment duration was 38 months; 60% of all patients remained enrolled at 3 years postdiagnosis. RESULTS: On average, patients with chronic kidney disease and diabetes and those with chronic kidney disease and hypertension remained enrolled slightly longer than chronic kidney disease-only patients (39 months, 40 months, and 36 months, respectively). The largest number of claims was for inpatient medical, followed by pharmacy and laboratory. Mean annual direct healthcare costs were higher for patients with chronic kidney disease and diabetes ($20,165) and those with chronic kidney disease and hypertension ($17,612) compared with patients with chronic kidney disease only ($9390). CONCLUSION: The study findings indicate that most patients who are newly diagnosed with chronic kidney disease retain their health plan affiliation for a considerable period, including those with diabetes or hypertension. Increased direct healthcare costs were associated with the presence of comorbidities in patients with chronic kidney disease. PMID- 25126301 TI - Management tools for molecular diagnostic testing: financial and clinical implications. PMID- 25126302 TI - Increases in Drug Utilization and Patent Expirations: A Recipe for Growth of Generics' Market Share, despite Stalling on Biosimilars. PMID- 25126303 TI - Quality improvement initiatives: the missed opportunity for health plans. AB - BACKGROUND: The increase in healthcare cost without direct improvements in health outcomes, coupled with a desire to expand access to the large uninsured population, has underscored the importance of quality initiatives and organizations that provide more affordable healthcare by maximizing value. OBJECTIVES: To determine the knowledge of managed care organizations about quality organizations and initiatives and to identify potential opportunities in which pharmaceutical companies could collaborate with health plans in the development and implementation of quality initiatives. METHODS: We conducted a survey of 36 pharmacy directors and 15 medical directors of different plans during a Managed Care Network meeting in 2008. The represented plans cover almost 74 million lives in commercial, Medicare, and Medicaid programs, or a combination of them. RESULTS: The responses show limited knowledge among pharmacy and medical directors about current quality organizations and initiatives, except for quality organizations that provide health plan quality accreditation. The results also reveal an opportunity for pharmaceutical companies to collaborate with private health plans in the development of quality initiatives, especially those related to drug utilization, such as patient adherence and education and correct drug utilization. CONCLUSION: Our survey shows clearly that today's focus for managed care organizations is mostly limited to the organizations that provide health plan quality accreditation, with less focus on other organizations. PMID- 25126305 TI - Orphan drug pricing and payer management in the United States: are we approaching the tipping point? AB - The Orphan Drug Act of 1983 paved the way for the development of drugs that treat rare diseases, defined in the United States as those affecting fewer than 200,000 patients. Orphan drugs can cost hundreds of thousands of dollars annually, but insurers have traditionally covered these therapies because the small populations involved did not typically lead to significant cost exposure. Payer sensitivity to the cost of orphan drugs is rising, however, with the accelerated rate of new launches of these agents amid intensified economic pressure. Payers are showing increasing levels of concern and scrutiny about coverage of orphan drugs. A new payer survey conducted between February 2008 and March 2009 provides insights on how payers are managing orphan drugs and the way it is likely to evolve in the future. Survey findings show that the patient share of orphan drug costs is rising and is expected to continue to rise, barring sweeping changes in public health policy. This shift in benefit design could affect patient access to orphan agents and, therefore, drug utilization. Manufacturers will have to invest in research to understand payer impact on the uptake of their orphan drugs in development. They will also benefit from being prepared to develop strategies to ensure patient access to and affordability of their orphan agents. PMID- 25126304 TI - Economic Evaluation of Quality-of-Life Improvement with Second-Generation Antihistamines and Montelukast in Patients with Allergic Rhinitis. AB - BACKGROUND: Allergic rhinitis causes significant economic losses and substantial reductions in quality of life. Improving a patient's symptoms can therefore enhance the patient's quality of life. OBJECTIVE: To measure the relative cost effectiveness of prescription second-generation antihistamines (levocetirizine, desloratadine, and fexofenadine) and montelukast based on their impact on quality of life in patients with uncomplicated allergic rhinitis. METHODS: A retrospective, cost-effectiveness model was constructed using 1-year costs to managed care payers and using the Rhinoconjunctivitis Quality of Life Questionnaire to measure the quality of life in patients taking prescription second-generation antihistamines or montelukast for the treatment of allergic rhinitis. Clinical trial results for levocetirizine, desloratadine, fexofenadine (brand and generic), or montelukast were combined as standardized mean differences to create a pooled effectiveness measure. The costs of prescription drugs and physician office visits for allergic rhinitis were used as direct costs measures. Sensitivity was assessed by a Monte Carlo simulation run 1000 times. RESULTS: All the drugs in the study showed significant improvement in quality of life, with levocetirizine showing the greatest improvement. The incremental cost effectiveness of levocetirizine dominated montelukast (incremental cost-effective ratio, -1317; 95% confidence interval, -7471, -212). The incremental cost effectiveness favored levocetirizine compared with desloratadine and branded fexofenadine. CONCLUSION: There are significant differences in the cost effectiveness of various oral prescription agents with regard to improving quality of life of patients with allergic rhinitis. PMID- 25126306 TI - Competition from biosimilars an incentive for innovation. PMID- 25126307 TI - Physicians' perceptions of reimbursement as a barrier to comprehensive diabetes care. AB - BACKGROUND: As the incidence of diabetes increases, there is growing concern about the adequacy of reimbursement levels for delivering comprehensive diabetes care. OBJECTIVE: To investigate physicians' perceptions of the adequacy of reimbursement, as well as resources (eg, staff, facilities, materials), for their treatment of diabetic patients. METHODS: A qualitative exploration using a Web based survey of 300 physicians (200 primary care providers and 100 endocrinologists) and an online discussion group of 12 physicians, focusing on 10 services recommended by the American Diabetes Association that may be prone to underreimbursement. The 10 services were matched with 4 general diabetes care categories to assess the adequacy of care delivery. RESULTS: The majority of physician study participants perceived that most of the 10 identified services are inadequately reimbursed-83% to 95% of physicians said Medicaid reimbursement was inadequate, 75% to 89% for Medicare reimbursement, and 67% to 86% for private insurance reimbursement-leading them to spend less time with each patient. This reduction in time was a limiting factor to providing comprehensive diabetes care. The survey also revealed differences between endocrinologists and primary care physicians; for example, medical nutrition therapy was offered by 50% of endocrinology practices compared with only 29.5% of primary care practices. CONCLUSION: This study confirms previous findings that physicians perceive current reimbursement for diabetes care as too low, which limits their ability to perform all the tasks necessary to deliver comprehensive diabetes care. PMID- 25126309 TI - Pharmacogenomics and drug development. PMID- 25126308 TI - Hypertension management: an update. AB - Hypertension is a significant and costly public health problem. It is a major, but modifiable contributor for the development of cardiovascular disease. Randomized controlled trials have shown that controlling hypertension reduces the risk of stroke, coronary artery disease, congestive heart failure, end-stage renal disease, peripheral vascular disease, as well as overall mortality. The risk of developing these hypertension-related complications is continuous, starting at a blood pressure level as low as 115/75 mm Hg. Despite the inherent health risks associated with uncontrolled hypertension, elevated blood pressure remains inadequately treated in the majority of patients. This article reviews guidelines for optimal evaluation of hypertension and current therapeutic options available to combat this common yet pervasive disease. PMID- 25126310 TI - Obesity: effective treatment requires change in payers' perspective. AB - BACKGROUND: Obesity is an increasing problem in the United States, and the health problems attributed to it have a significant economic impact on the healthcare system, as well as on patients' quality of life. In addition, childhood obesity is increasingly becoming a prominent diagnosis. OBJECTIVE: To identify physician and payer reactions to the profiles of 4 new obesity products in development and the potential that these will be prescribed by physicians and reimbursed by payers. This article examines payers' and physicians' perspectives in effective treatment options for this epidemic. METHOD: A 2008 online survey conducted by Reimbursement Intelligence was completed by 42 physicians who are advisors to Pharmacy & Therapeutics Committees and see an average of 435 obese patients monthly, as well as 17 payers who represent more than 100 million covered lives. This research was double blinded to conceal product and client identification. Qualitative and quantitative data were collected from the survey responses. RESULTS: Based on the physician and payer survey responses, morbid obesity is expected to grow in the next 2 years. About 80% of morbidly obese patients have type 2 diabetes, but more than 75% of payers do not track patients who are obese, morbidly obese, or those with the metabolic syndrome. Despite its effect on business productivity and the cost of care, healthcare professionals and payers continue to have varying perspectives related to its prevention and treatment. Physicians would like to have more treatment options, but payers perceive them as ineffective and find the safety and adverse effect profiles unfavorable. CONCLUSION: There is a clear need for multiple treatment alternatives to combat obesity that include plan member access to weight-loss options, such as prescription medications and bariatric surgery. There needs to be an increase in educational support from manufacturers of products for obesity, as well as increased awareness of products in the pipeline. PMID- 25126311 TI - Health insurance premium increases for the 5 largest school districts in the United States, 2004-2008. AB - BACKGROUND: Local school districts are often one of the largest, if not the largest, employers in their respective communities. Like many large employers, school districts offer health insurance to their employees. There is a lack of information about the rate of health insurance premiums in US school districts relative to other employers. OBJECTIVE: To assess the change in the costs of healthcare insurance in the 5 largest public school districts in the United States, between 2004 and 2008, as representative of large public employers in the country. METHODS: Data for this study were drawn exclusively from a survey sent to the 5 largest public school districts in the United States. The survey requested responses on 3 data elements for each benefit plan offered from 2004 through 2008; these included enrollment, employee costs, and employer costs. RESULTS: The premium growth for the 5 largest school districts has slowed down and is consistent with other purchasers-Kaiser/Health Research & Educational Trust and the Federal Employee Health Benefit Program. The average increase in health insurance premium for the schools was 5.9% in 2008, and the average annual growth rate over the study period was 7.5%. For family coverage, these schools provide the most generous employer contribution (80.8%) compared with the employer contribution reported by other employers (73.5%) for 2008. CONCLUSIONS: Often the largest employers in their communities, school districts demonstrate a commitment to provide choice of benefits and affordability for employees and their families. Despite constraints typical of public employers, the 5 largest school districts in the United States have decelerated in premium growth consistent with other purchasers, albeit at a slower pace. PMID- 25126312 TI - First anti-inflammatory generic drug promising new therapy for diabetes. PMID- 25126313 TI - Evolving trends in insulin delivery in pursuit of improvements in diabetes management. AB - Diabetes mellitus affects 23.6 million Americans and its incidence is rapidly increasing, particularly in older, overweight patients. Large-scale studies conclusively show that elevated blood glucose levels are associated with an increased risk for microvascular complications, such as retinopathy and nephropathy. The high rates of morbidity and mortality associated with this disease, and the costs associated with it, underscore the importance of effective glycemic control. Conventional syringe/vial insulin delivery is associated with many barriers for patients with diabetes mellitus and for their healthcare providers. Substantial developments in insulin delivery show promise in overcoming these barriers. New technologies in insulin delivery focus on increasing patient convenience, reducing the frequency of daily injections, and improving glycemic control. This article outlines the challenges associated with conventional insulin delivery and describes recent developments that may help to overcome these barriers and, ultimately, could enhance glycemic control. PMID- 25126314 TI - Healthcare costs associated with switching from brand to generic levothyroxine. AB - BACKGROUND: Controversy exists over the true therapeutic equivalence of branded and generic levothyroxine-the drug of choice for treating hypothyroidism-so professional societies recommend against switching between different formulations of the drug and suggest that patients who do switch be monitored. Payers typically encourage switching to generic drugs because of lower drug acquisition costs. OBJECTIVE: To evaluate the impact of switching levothyroxine formulations on actual healthcare costs. METHODS: Patients with hypothyroidism and at least 6 months of branded levothyroxine therapy were identified from a large healthcare claims database. Patients who subsequently switched to another levothyroxine formulation and could be followed for 6 months postswitch were matched to demographically similar patients who were continuous users of branded levothyroxine. Pre- and postswitch healthcare costs for each group were compared. RESULTS: The savings in prescription drug costs after switching from branded to generic levothyroxine are offset by increases in costs for other healthcare services, such that switching is actually associated with an increase, not a decrease, in total healthcare costs. CONCLUSION: In the absence of cost-savings, there is no clear rationale for switching patients from brand to generic levothyroxine. PMID- 25126316 TI - Accountable care organizations in the era of healthcare reform. AB - Under the Patient Protection and Affordable Care Act (PPACA) of 2010, Medicare providers, including physician groups and hospitals, will soon have the option to form accountable care organizations (ACOs) to improve quality and efficiency. ACO participants may share financial gains generated from improved clinical and economic performance, provided that quality goals and patient safeguards are met. Through future regulations, the Centers for Medicare & Medicaid Services (CMS) must implement the ACO option no later than January 1, 2012. In this interview, Dr Mark B. McClellan, former CMS Administrator and US Food and Drug Administration Commissioner, discusses the extraordinary implications of the new ACO option for improving patient care and reducing unnecessary costs. PMID- 25126315 TI - Pay-for-Performance Initiatives: Modest Benefits for Improving Healthcare Quality. AB - BACKGROUND: Pay-for-performance initiatives have been suggested as a way to improve the quality of patient care and provide incentives to improve providers' performance. The Centers for Medicare & Medicaid Services has endorsed such programs to improve quality of care. OBJECTIVE: To examine the state of quality initiatives endorsed by the Centers for Medicare & Medicaid Services in which institutions, provider groups, and physicians are awarded incentives based on adherence to composite metrics. METHOD: A literature search was conducted using the keywords "pay-for-performance," "quality improvement," "medical errors," and "physician incentive plans." RESULTS: Although quality of care has improved in healthcare settings that engage in pay-for-performance initiatives, what can be attributed to payer-incentive programs is uncertain. Studies demonstrate that, of the 25 hospitals classified by the Centers for Medicare & Medicaid Services to be in the lowest decile of quality improvements, all still made significant progress in adhering to quality metrics after participation in the study. Financial rewards, however, were distributed based on a predetermined threshold established by the Centers for Medicare & Medicaid Services to be given only to participants who fell in the top 2 deciles. Penalties were incurred by the 51 hospitals that were within the bottom 2 deciles despite making substantial improvements. At such institutions, large minority communities and Medicaid populations comprise the patient populations. Other pay-for-performance schemes, such as employer-based purchasing, consumer health-spending accounts, and collaborative groups, were studied, with little data to support definite benefits. CONCLUSIONS: Examining rates of improvement in adherence to pay-for-performance initiatives when determining how to distribute financial rewards should be studied alongside the current classification by absolute deciles. By rewarding rates of improvement, potential elimination of quality disparities for hospitals that serve large Medicaid and minority populations can be achieved, because such organizations are encouraged to invest in quality improvement as a result of substantial progress made. Although alternative strategies like employer-driven value-based purchasing and collaboratives seem promising, the long-term effects of such initiatives still need to be studied. Creating greater financial incentives for individual providers to participate in pay-for-performance programs for many years to come will remain a challenge. PMID- 25126317 TI - Expect the unexpected: a role for behavioral economics in understanding the impact of cost-sharing on emergency department utilization. AB - BACKGROUND: AS EMPLOYERS AND PAYERS ADDRESS INCREASING HEALTHCARE COSTS, THEY RESORT TO THE TENETS OF CLASSICAL ECONOMICS: if one increases the price for a service (defined as an individual's cost-sharing), then that individual's demand for services should decrease. This, however, may not necessarily be true, and raises the question of whether increased cost-sharing for emergency department services will lead to decreased utilization of those services as would be expected in classical economics. OBJECTIVE: To assess the effect of emergency department cost-sharing on patient utilization of emergency department services. METHOD: In 2002, we retrospectively reviewed 2001 claims and identified 797 members who have had at least 2 nonemergent visits to the emergency department. This cohort was comprised of members with high emergency department utilization patterns who also had potentially differing emergency department copayment changes from one health insurance plan year to the next. Participants had to be covered by Humana for a minimum of 12 consecutive months. Of the original cohort, 415 remained covered by Humana after the end of the first year, 322 remained covered after the second year, and 194 after the end of the third year. After completions of three 12-month blocks of time with appropriate claims run out, we assessed changes in the cohort's emergency department encounters from the previous year to the current year relative to emergency department copayment changes, using matched pairs t-test. RESULTS: Surprisingly, in the first 12 months, reductions in emergency department copayments resulted in decreases in patient utilization (-58.3% change, P <.007), and increases in emergency department copayment resulted in an increased utilization (1096.0% change, P <.001). This unexpected trend continued in the second and third periods. Overall, in our cohort, increases in emergency department copayments were significantly associated with increased emergency department encounters by different individuals in each of the 3 study periods. In contrast, in the 2 groups with no increases in emergency department copayments, utilization of these services decreased or remained flat. CONCLUSION: When assessing the need for emergency department services, many factors besides cost play a role in choosing to obtain emergency department care, including individual assessments of the probability of a given illness and the financial or temporal implications for the care sought in terms of "gains" or "losses" relative to a reference point. Behavioral economics can therefore play a role in understanding why healthcare consumers behave as they do. The implications of behavioral economics need to be factored in when considering a healthcare benefit design. PMID- 25126318 TI - The new accountable care organizations and medicare gain-sharing program. PMID- 25126320 TI - Enhanced Generic Utilization Saved US Healthcare $139.6 Billion in 2009. PMID- 25126319 TI - Effectiveness of anti-tumor necrosis factor agents in the treatment of rheumatoid arthritis: observational study. AB - OBJECTIVE: The efficacy of anti-tumor necrosis factor therapies in rheumatoid arthritis has been demonstrated in randomized clinical trials. The purpose of the present study was to evaluate the effectiveness of these agents for the treatment of rheumatoid arthritis in a real-world setting. METHOD: This retrospective chart review included patients from 6 clinics in the United States. Eligibility criteria included age >=18 years, diagnosis of rheumatoid arthritis, and having been initiated with anti-tumor necrosis factor therapy (ie, adalimumab, etanercept, or infliximab) between January 1, 2002, and November 30, 2004. Patients were assessed for up to 2 years after therapy initiation. Primary outcomes of interest were improvements in 4 effectiveness measures-joint pain, joint swelling, joint stiffness, and fatigue. A total of 496 patients met the study's inclusion criteria: 84 (16.9%) in the adalimumab group, 146 (29.4%) in the etanercept group, and 266 (53.6%) in the infliximab group. RESULTS: Improvement in 1 of the 4 effectiveness measures was documented in 36.8% (n = 25) who received adalimumab, in 47.7% (n = 62) of those who received etanercept, and in 48.7% (n = 115) of patients who received infliximab. The infliximab group was the only cohort to demonstrate significant improvements from baseline in joint pain, joint swelling, and joint stiffness. The adalimumab group had significant improvement in joint pain (P = .004). No significant change in fatigue scores was reached with any of these agents. CONCLUSION: In the real-world setting of patients with rheumatoid arthritis, anti-tumor necrosis factor therapy shows significant improvements in joint pain, joint swelling, and joint stiffness, although there are differences in effectiveness in the 4 measures among the 3 agents assessed in this study. PMID- 25126321 TI - Comparing medical cost of care for patients with metastatic breast cancer receiving taxane therapy: claims analysis. AB - BACKGROUND: It has been estimated that more than $8 billion is spent annually on the management of breast cancer in the United States. The taxane chemotherapeutic agents are cornerstones in the treatment of breast cancer, yet no study has assessed whether the choice of a taxane affects the economic outcomes of metastatic breast cancer treatment. OBJECTIVE: To determine if differences exist in the medical cost of care in patients receiving taxane-based chemotherapy for metastatic breast cancer, and to compare the use of ancillary medications (for neutropenia, anemia, and nausea and vomiting) and their associated costs among taxanes. METHOD: We identified women with metastatic breast cancer based on diagnosis codes and the women's previous adjuvant chemotherapeutic regimens. Paid medical insurance claims were captured for the 24-month study period, from January 1, 2006, through December 31, 2007. The groups were determined according to the specific taxane administered. Total medical costs were captured from the date of first taxane administration to the end of data availability. Outpatient pharmacy costs were not available. A multivariate analysis was used to evaluate the total medical costs in each group. Median total medical costs per patient per month during the study period were adjusted using a multiple regression analysis. Utilization and cost of medications administered in the office or hospital for chemotherapy-induced adverse effects were captured and adjusted with Tobit models. RESULTS: Of the 2245 study participants, 1035 received docetaxel, 997 received generic paclitaxel, and 213 received nab-paclitaxel. On average, patients in the nab-paclitaxel group received more doses (9.6) than those in the generic paclitaxel (6.0) or docetaxel (4.8) groups. The multivariate analysis was robust, explaining 72% of the variability in total medical costs across the 3 taxane groups. Median per-patient per-month total medical costs for study participants were within approximately $800 of each other among the groups. Generic paclitaxel had the lowest total medical costs. The total costs for docetaxel and nab-paclitaxel were not significantly different. Nab-paclitaxel had the lowest utilization and lowest costs associated with colony-stimulating factors. The proportion of patients receiving erythropoiesis-stimulating agents was not significantly different among the 3 drugs, but the costs for these agents were significantly lower in patients receiving nab-paclitaxel than in those receiving docetaxel. Antiemetic use was highest in the docetaxel group, but the costs for antiemetics were not different among the 3 taxane groups. CONCLUSION: The differences in total medical costs among the 3 taxanes were modest. Total medical costs were lowest for patients receiving generic paclitaxel and comparable between the docetaxel and nab-paclitaxel groups. Patients taking nab paclitaxel received more doses than patients taking the other taxanes. Nab paclitaxel was associated with lower utilization and costs for colony-stimulating factors compared with generic paclitaxel and docetaxel. PMID- 25126322 TI - The impact of healthcare reform on payers' products, provider reimbursement, and member engagement. PMID- 25126323 TI - The current state of bundled payments. PMID- 25126324 TI - Assessment of medicare part d communications to beneficiaries. AB - BACKGROUND: Older Americans receive healthcare benefits through the federal Medicare program. The Centers for Medicare & Medicaid Services provides comprehensive information to Medicare beneficiaries regarding benefits, plan options, and enrollment policies primarily through the annual Medicare & You handbook and the Medicare website. Few studies have assessed the overall readability and, therefore, the usefulness of this handbook for adequately educating beneficiaries. Healthcare communications written at higher levels than the readers' comprehension levels cannot be well understood. OBJECTIVE: To measure the readability of the 2008 Medicare & You handbook provided to all Medicare beneficiaries. METHOD: For our analysis, the 2008 version of the Medicare & You handbook was downloaded from the Centers for Medicare & Medicaid Services website. Passages of >=250 words were saved individually in Windows Notepad as text files. Shorter passages (ie, <250 words) were combined with the next continuing passage. Each file was then uploaded into the Internet-based Lexile analyzer (the Lexile Framework for Reading). Figures, pictures, and tables were not included in the analysis. RESULTS: Approximately 70% of analyzed passages were written at approximately the 5th- to 12th-grade levels (Lexile scores: 790L-1290L), whereas 30% of the passages were written at levels above grade 12 (Lexile scores: 1310L-1910L). CONCLUSION: Medicare beneficiaries who have less than a high-school level education may find the passages analyzed in this study difficult to read and comprehend as discussed, indicating the need for simplified communication. Our study provides recommendations to improve the handbook for better comprehension by beneficiaries. PMID- 25126326 TI - FDA's Approval Process Borne Out by a Large Study: But Communicating Generics' Safety and Efficacy to the Public Leaves Much to Be Desired. PMID- 25126325 TI - A comparison of drug formularies and the potential for cost-savings. AB - BACKGROUND: Brand-name drug costs have been escalating in the United States, and the reasons for this are not immediately clear. A lack of adequate and accurate information about drug effectiveness, safety, and cost has implications for drug utilization and cost. OBJECTIVE: To explore the extent to which health plan formularies were consistent with recommended drug listings and identify what would be the potential cost-savings on total drug expenditures if the utilization rate of the recommended therapies was increased. METHOD: This study compared publicly available recommended drug listings with the formularies of 8 major health plans in Minnesota. Data from 1 of the health plans underwent an in-depth case analysis to evaluate the potential impact on pharmaceutical expenditures, using increased utilization rate scenarios of the recommended drugs. RESULTS: Health plans were similar with respect to degree of coverage for the recommended drugs. However, the case analysis showed that by increasing the utilization rate of recommended drugs, a potential cost-savings of more than 50% could be realized for the evaluated health plan for some therapeutic categories. CONCLUSION: This study demonstrates an approach to assessing drug formularies using publicly available, recommended drug lists that incorporated evidence for effectiveness, safety, and cost. By using the application of this type of reliable information, formulary changes can be guided to incentivize value-based utilization for patient populations. PMID- 25126328 TI - Healthcare reform: quality outcomes measurement and reporting. PMID- 25126327 TI - Managing dyslipidemia in primary care with restricted access to lipid-modifying therapy. AB - BACKGROUND: Many patients with dyslipidemia do not achieve goal low-density lipoprotein cholesterol levels. The barriers to achieving goal include inadequate assessment of cardiovascular risk status, medication cost, formulary restrictions, patient lack of adherence, and inadequate counseling time. Removing barriers may improve goal attainment and reduce the risk for cardiovascular events. OBJECTIVE: To identify opportunities to improve dyslipidemia management in primary care by examining low-density lipoprotein cholesterol goal attainment in patients with unrestricted or restricted access to lipid-modifying therapy. METHOD: A total of 5936 adult patients from a primary care practice with a low density lipoprotein measurement were categorized by coronary heart disease risk into 1 of 4 lipid-modifying therapy groups: unrestricted (fluvastatin, lovastatin, pravastatin, or simvastatin monotherapy); restricted (atorvastatin, rosuvastatin, or simvastatin/ezetimibe fixed-dose combination); other (lipid modifying combination statin therapy or a nonstatin lipid-modifying therapy); and no lipid-modifying therapy. The primary outcome was low-density lipoprotein cholesterol goal attainment by lipid-modifying therapy group. Logistic regression identified associated demographic and clinical factors. RESULTS: In this cohort, 78.1% of the patients achieved low-density lipoprotein cholesterol goal levels. Overall goal attainment rates were lower in the high and very high coronary heart disease risk categories, at 52.6% and 31.6%, respectively. For patients at elevated coronary heart disease risk (high or very high), the rates of low density lipoprotein cholesterol goal attainment were 14 to 16 percentage points higher for patients receiving restricted lipid-modifying therapy compared with patients receiving unrestricted lipid-modifying therapy (high coronary heart disease risk: 68% vs 52%, respectively; very high coronary heart disease risk: 42% vs 28%, respectively). Increasing age, male sex, and use of restricted lipid modifying therapy were significantly associated with improved low-density lipoprotein cholesterol goal attainment. Of the 1298 patients who were not at low density lipoprotein cholesterol goal, 54.1% were not receiving any lipid modifying therapy. For each coronary heart disease risk category, there was a significantly higher percent utilization of unrestricted lipid-modifying therapy compared with restricted lipid-modifying therapy (P <.001). CONCLUSION: A significant number of patients at elevated risk for coronary heart disease remain untreated or have low-density lipoprotein cholesterol levels above target. Removing barriers to the use of restricted lipid-modifying agents in patients at risk for heart disease provides an opportunity to improve low-density lipoprotein cholesterol levels. PMID- 25126329 TI - Implications of the new political realities on healthcare reform. AB - With the recent change in power in the US House of Representatives that will take effect in January, questions arise regarding potential modifications to some features in the healthcare reform bill and its implementation. With many provisions scheduled to take effect between 2011 and 2014, the political implications of the elections have an immediate practical relevance to health plans, employers, and other healthcare stakeholders. American Health & Drug Benefits discussed some of these issues with Dan Mendelson, who served in the Clinton administration between 1997 and 2000, when there was a similar division of party power between Congress and the administration. PMID- 25126330 TI - Engaging providers in medication adherence: a health plan case study. AB - BACKGROUND: Nonadherence to treatment regimens is a common, costly, and complex problem that is often overlooked in a busy primary care setting. OBJECTIVE: The goals of this study were to raise providers' awareness of nonadherence among their patients, to identify the reasons for lack of adherence, and engage physicians in addressing these barriers. METHOD: Five primary care practices agreed to participate. The project began in the fall of 2008 with a therapy gap analysis, using prescription drug data from the previous 18 months to identify nonadherent patients. Initially, 237 members were identified as potential nonadherent patients. Each practice was presented with the data related to its patients; the group then narrowed its sample using a chart review and/or patient outreach. Each practice had to determine the barriers to adherence, and was then asked to create action steps to improve patient adherence based on the group's unique results and the specific patient population. RESULTS: Barriers to adherence identified included prescription drug cost, multiple medications and dosing schedules, and patient as well as family level of understanding and acceptance of disease state. Each group gained an awareness of nonadherence as it related to their patients. For example, in the internal medicine practice, 33% (n = 17) of the patients reported stopping their medication because of cost. A common reason for poor adherence in the pediatric groups was that parents decided to stop their child's medication on weekends and in the summer, without a physician's recommendation. Using such feedback, each practice then developed its own methods to improve medication adherence within its patient population. CONCLUSION: Although the final numbers in this case study were small, the providers gained valuable insights regarding nonadherence in their practice. This study shows the importance of engaging providers in medication adherence as a way to improve this common problem. Making this universal issue a personal problem for providers is key to overcoming many of the adherence barriers. PMID- 25126331 TI - Moving beyond good intentions: making collaborative care a successful reality. PMID- 25126332 TI - The h-e-B value-based health management program: impact on asthma medication adherence and healthcare cost. AB - BACKGROUND: Recent publications have shown that copayment reductions increase medication adherence above the effects of existing disease management programs, demonstrating an additive effect of combining a value-based insurance design with a disease management program. This effect, however, has yet to be demonstrated for medications used for the treatment of asthma. OBJECTIVE: To evaluate the impact of a value-based health management asthma program-which included providing patient education and lowering copayments for select asthma controller medications-on medication adherence and healthcare utilization and costs. STUDY DESIGN: The study involved a quasi-experimental intervention versus control group design of insured patients diagnosed with asthma. METHOD: After applying the inclusion/exclusion criteria for study participation, we obtained informed consent from the intervention group; those eligible to participate who did not return the forms served as the control group. The final sample size included 764 patients with asthma-298 in the intervention group and 466 in the control group. The intervention consisted of a reduction in copayment for select asthma controller medications from an average of $20 to $30 down to $5, as well as 3 mailings of educational materials for asthma management. Medical and pharmacy claims data for the study population were used to evaluate all study parameters and outcomes. Medication possession ratio was used to measure adherence to asthma controller medications. Statistical models were used to study differences in the 2 study groups during the 12-month follow-up period for adherence and cost outcomes. RESULTS: Participation in the value-based health management asthma program increased patients' 12-month medication adherence by 10 absolute percentage points in the intervention group (53.9% for intervention vs 43.9% for control group, P <.001) and significantly decreased average monthly medical costs ($170 intervention vs $229 control, P = .004). This increase in adherence resulted in greater monthly pharmacy costs ($181 intervention vs $124 control, P <.001). However, the increase in pharmacy costs was offset by lower medical costs, leading to a nonsignificant increase in average monthly total healthcare costs ($362 intervention vs $337 control, P = .276). CONCLUSION: Adoption of a value-based health management program that combines patient education with lowered copayments has a positive impact on medication adherence, resulting in a reduction in associated medical costs and no significant increase in total costs. PMID- 25126333 TI - When information is insufficient: inspiring patients for medication adherence and the role of social support networking. AB - BACKGROUND: A report presented by the RAND Corporation for the Agency for Healthcare Research and Quality recommends that patient self-management programs should include supportive coaching, and the World Health Organization has suggested that the enhancement of patient motivation and behavioral skills is crucial to increasing patient care adherence. The US healthcare reform legislation also provides incentives for evidence-based activities (eg, coaching) that promote healthy behaviors. OBJECTIVES: To review the current research on evidence-based coaching methods and their impact on medication adherence, as well as offer practical applications for such coaching interventions. DISCUSSION: The authors review the role of medication adherence in reducing the burden of chronic diseases, using the definitions of coaching and Network Coaching as a starting point for interventions that can enhance providers' skills in motivating patients to improve their treatment adherence. Practical examples are included throughout the article to illustrate the benefits of these coaching methods for patients and providers. The mnemonic COPE is used to assist providers in the recall of 4 significant coaching and Network Coaching concepts-connectedness and collaboration, open-ended questions, positive attitude, and encourage support. Following COPE can reinforce physicians and pharmacists in their attempt to improve patient medication adherence. CONCLUSION: The article presents healthcare providers, including physicians and pharmacists, with a rationale for developing evidence-based coaching skills and offers suggestions for the application of key coaching concepts. PMID- 25126334 TI - Postapproval Development Options in COPD: A Case Study in Value-Based Healthcare Systems. AB - BACKGROUND: Research and development activities in an era of globalization encounter a mosaic of providers, products, services, and intermediaries; regulatory and other government institutions; and consumers. The introduction of novel therapeutics into this environment mandates research programs that are relevant to the registration process, payers and purchasers, transparent pricing, and rule-driven business practices, while providing data relevant to marketing initiatives internationally. OBJECTIVE: To outline an example for clinical development programs that incorporate the perspective of multiple stakeholders into a portfolio of study designs to provide optimal data platforms that can resonate with diverse recipients. DISCUSSION: A contract research organization directly involved in the design, execution, and analysis of clinical trials for new drugs and devices across pharmaceutical and biotechnology companies provides a unique perspective regarding opportunities and challenges within the international clinical research environment. Drs Murphy, Antonini, and Lai, representing Worldwide Clinical Trials, utilize chronic obstructive pulmonary disease as a demonstration project exploiting its prevalence, direct and indirect costs, and the rapid infusion/diffusion of innovative therapy into practice as a rationale for focus, and illustrate methods of informing registration and technology assessments during a prototypical development process. CONCLUSION: By virtue of its chronicity, prevalence, and pattern of healthcare utilization, chronic obstructive pulmonary disease provides an ideal case for illustrating the application of clinical trial methodology that can facilitate data evaluation through the prism of multiple stakeholders. Adding an international dimension exacerbates system complexity and serves to illustrate the breadth of issues that can be addressed within this therapeutic area. PMID- 25126335 TI - Perspectives in value-based insurance design for patients with diabetes: assessment and application. AB - BACKGROUND: Value-based insurance design initiatives have been developed in an effort to reduce long-term healthcare costs and improve health quality. Value based insurance design promotes the use of services or therapies that have been shown to have clinical benefits that outweigh the cost, such as encouraging medication adherence, and discourages those that produce results that do not justify the cost. OBJECTIVE: The goal of this analysis is to determine the impact of value-based insurance design as it relates specifically to drug therapy, including adherence, for patients with diabetes. METHOD: This article analyzes data collected by Milliman, a large actuarial group, using MedStat claims, National Health and Nutrition Examination Surveys, and its own 2008 health cost guidelines to develop an actuarial assessment of value-based insurance design programs for diabetes care and therapy. This assessment models the impact that copay structures and other management techniques have on adherence and incremental costs. The model provides a framework for assessing the value of benefits and directs patients toward cost-effective services supported by strong evidence-based medicine. DISCUSSION: Analysis of actuarial modeling shows that adjusting patient copayment designs is in line with other value-based approaches designed to improve patient care and reduce long-term costs. Evidence from value based insurance design initiatives suggests that reducing patient copayment has the potential to improve clinical outcomes, including medication adherence, and reduce overall healthcare costs. CONCLUSION: This analysis, coupled with results from other value-based insurance design initiatives and related research, provides support for employers and health insurance plans to consider adopting value-based insurance design programs for patients with diabetes to improve quality of care, while potentially reducing healthcare costs. PMID- 25126337 TI - First Generic ARB Approval Draws a Wave of Comparative Studies. PMID- 25126336 TI - Addressing Costs and Continuity of Care through Innovative Solutions for Infused Therapies: A Collaborative Experience with Infliximab. AB - BACKGROUND: Infused therapies are becoming more common as pharmaceutical and biotechnology companies increasingly focus their research and development efforts on biologic agents. OBJECTIVE: To understand how collaborative efforts among a health plan, providers, and specialty pharmacies can improve the efficiency of delivering infused therapies, using the example of a pilot program in southern Ohio for the administration of infliximab. METHODS: In October 2008, the authors conducted one-on-one, in-person interviews with representatives of a health plan, a specialty pharmacy, and the 3 largest gastroenterology practices in a southern Ohio community that collaborated to develop an innovative pilot program for delivering infliximab for patients with inflammatory bowel disease in a cost effective manner in the office setting. The 2 health plan and 1 specialty pharmacy representatives were directly involved with the development and implementation of the program. Gastroenterology practice representatives included 3 practice managers, 2 infusion nurses, 2 billing managers, and 1 precertification specialist. RESULTS: The interviews revealed the opportunities and challenges associated with managing infused therapies, as well as the potential unintended consequences of unilateral action by health plans. As a result of changes introduced by a local health plan in southern Ohio, 3 of the largest gastroenterology practices in the region decided to discontinue in-office infliximab infusions for their patients and send them to local hospital outpatient infusion centers. However, before the implementation of this policy, a new collaboration between the health plan, the 3 practices, and the health plan's specialty pharmacy enabled these practices to continue to provide this medication in their offices. This collaboration avoided cost increases to all involved by preventing the shift of patients to hospital outpatient departments and allowing patients to continue their care in the office setting. CONCLUSION: It will become increasingly important for payers to develop and support cost-effective ways to provide physicians and patients with access to infused medications. This pilot program shows the benefits of collaboration among healthcare stakeholders to identify innovative solutions for delivering appropriate office-based infusion therapy. The specific approach that is most appropriate for a specific health plan will depend on the unique local market circumstances. PMID- 25126338 TI - Five steps healthcare leaders can take to address childhood obesity. PMID- 25126339 TI - Comparative effectiveness research in the United States: a catalyst for innovation. AB - Recent calls for value in the US healthcare system have spurred an increase in comparative effectiveness research, which generates evidence on competing treatment options to inform healthcare stakeholders. As a large healthcare purchaser, the federal government has made several significant investments in comparative effectiveness research. Notably, in 2009 the American Recovery and Reinvestment Act allocated $1.1 billion for comparative effectiveness research, and in 2010 the Patient Protection and Affordable Care Act established a federal institute to organize the federal investment in comparative effectiveness research going forward. Over the past several years, comparative effectiveness research from the public and private sectors has begun to provide a foundation for innovation within the insurance and life sciences industries. Health plans and other payers are experimenting with nuanced coverage and reimbursement policies informed by comparative effectiveness evidence. Anticipating changes in payer, patient, and provider behaviors, drug manufacturers are refocusing their efforts on the development of novel and better-differentiated medications. As more comparative research becomes available in the future, continued innovation in payer and manufacturer strategies appears likely. PMID- 25126341 TI - Recent trends in the dispensing of 90-day-supply prescriptions at retail pharmacies: implications for improved convenience and access. AB - BACKGROUND: Mail-service pharmacies offer consumers the convenience of prescriptions filled with a 90-day supply of medication. Unlike mail-service pharmacies, retail pharmacies traditionally dispensed maintenance medication prescriptions with a 30-day supply. However, the retail landscape changed in May 2008 with Walmart's announcement of an extension of its $4 Prescription Program to include 90-day-supply prescriptions. OBJECTIVE: To evaluate recent changes in access to and use of 90-day-supply maintenance medications dispensed via retail pharmacy. SUMMARY: As of the first quarter of 2007, the proportion of retail dispensed maintenance medications with a 90-day supply (compared with all maintenance prescriptions dispensed) among Medicare Part D plans, self-insured employers, and private health plans was 5.1%, 5.1%, and 5.0%, respectively. As of December 2009, this ratio had risen to 8.0% for Medicare plans and 8.1% for commercial health plans; the ratio among employers had risen more modestly to 6.1%. Of particular interest and importance, the proportion increased similarly for brand and for generic medications. CONCLUSION: There has been substantial growth in 90-day prescriptions dispensed via retail pharmacy, a trend that is likely to continue as more insurance providers adopt compatible benefit designs. It is important to continue monitoring these trends and to identify opportunities to rigorously evaluate their impact on medication adherence and healthcare costs. PMID- 25126340 TI - Comparing treatment persistence, healthcare resource utilization, and costs in adult patients with major depressive disorder treated with escitalopram or citalopram. AB - BACKGROUND: Major depressive disorder is the most common type of depression, affecting 6.6% of adults in the United States annually. Citalopram and escitalopram are common second-generation antidepressants used for the treatment of patients with this disorder. Because citalopram is available in generic forms that have lower acquisition costs compared with the branded escitalopram, some health plans may provide incentives to encourage the use of the generic option. Decisions based solely on drug acquisition costs may encourage the use of a therapy that is less cost-effective when treatment persistence, healthcare utilization, and overall costs are factored in. OBJECTIVE: To compare, in a real world setting, the treatment persistence, healthcare utilization, and overall costs of managing adult patients with major depressive disorder who are treated with escitalopram or citalopram. METHODS: Administrative claims data (from January 1, 2003, to June 30, 2005) were analyzed for patients with major depressive disorder aged >=18 years. Patients filled >=1 prescriptions for citalopram or for escitalopram (first-fill time was defined as the index date) and had no second-generation antidepressant use during the 6-month preindex period. Treatment persistence, healthcare utilization, and healthcare costs were measured over the 6-month preindex and 6-month postindex periods and compared between patients treated with citalopram or escitalopram, using unadjusted and multivariate analyses. RESULTS: Patients receiving escitalopram (N = 10,465) were less likely to discontinue the treatment (hazard ratio 0.94; P = .005) and switch to another second-generation antidepressant (hazard ratio 0.83; P <.001) than patients receiving citalopram (N = 4212). Patients receiving escitalopram were also less likely to have a hospital admission (odds ratio 0.88; P = .036) or an emergency department visit and had lower total healthcare costs (-$1174) and major depressive disorder-related costs (-$109; P <.001) during the study period. CONCLUSION: Although the drug acquisition costs are lower for generic citalopram than for the brand-name escitalopram, patients treated with escitalopram had better treatment persistence, lower healthcare utilization, and lower overall costs compared with patients treated with citalopram over the study period. This may suggest that other considerations, in addition to acquisition cost, may need to be factored in to assess the cost-effectiveness of drug therapy. PMID- 25126343 TI - New economic analysis zeroes in on low generic utilization and waste in medicaid. PMID- 25126344 TI - CMS Invites Feedback on the Proposed Accountable Care Organizations Rules. PMID- 25126342 TI - Strategies to prevent opioid misuse, abuse, and diversion that may also reduce the associated costs. AB - BACKGROUND: The use of prescription opioid drugs has the potential to lead to patient abuse of these medications, addiction, and diversion. Such an abuse is associated with increased costs because of excessive healthcare utilization. Finding ways to minimize the risk for abuse and addiction can enhance patient outcomes and reduce costs to patients and to payers. OBJECTIVE: To review current strategies that may reduce the risk for misuse and abuse of opioid medications, which in turn can enhance patient outcomes and lower costs to health insurers and patients. DISCUSSION: Implementing approaches that will encourage the use of safe practices (universal precautions) in pain management by providers can reduce the risk for abuse and misuse associated with chronic pain medications, especially opioids. These approaches include, but are not limited to, extensive physician and patient education regarding these medications and their associated risks for abuse; the development of prescription monitoring programs to detect physician or pharmacy shopping; the detection of inappropriate prescribing and medical errors; the use of physician-patient contracts concerning opioid treatment; the requirement of presenting a photo identification to pick up an opioid prescription at the pharmacy; urine drug toxicology screening; provisions for safe disposal of unused opioids; referrals to pain and addiction specialists; and potentially encouraging the use of opioid formulations aimed at reducing abuse. CONCLUSION: Supporting such approaches by health insurers and educating providers and patients on the risks associated with chronic pain medications can help minimize the risk of prescription opioid abuse, addiction, and diversion; reduce health services utilization associated with opioid abuse; improve patient outcomes; and reduce overall costs. PMID- 25126345 TI - The patient-centered medical home: an essential destination on the road to reform. PMID- 25126347 TI - Systematic health management: the time has come to do the right thing for each person. PMID- 25126346 TI - Utilization, spending, and price trends for short- and long-acting Beta-agonists and inhaled corticosteroids in the medicaid program, 1991-2010. AB - BACKGROUND: Asthma is a chronic respiratory disease that afflicts millions of people and accounts for substantial utilization of healthcare resources in most industrialized countries, including in the United States. However, the exact cost and utilization of anti-asthma medications in Medicaid in the past 2 decades have not been well studied. Considering the safety issues surrounding the long-acting beta-agonists, guideline updates, and the increase in asthma prevalence, understanding anti-asthma medication prescribing trends is important to payers and patients. GOAL: The purpose of this study was to analyze the utilization and spending trends for anti-asthmatic agents in the US Medicaid program over the past 2 decades. METHODS: This study was based on a retrospective, descriptive analysis of trends in utilization of and spending on anti-asthma medications, including short-acting beta-agonists, inhaled corticosteroids, long-acting beta agonists, and inhaled corticosteroid/long-acting beta-agonist combinations. Quarterly utilization and expenditure data were obtained from the national Medicaid pharmacy files provided by the Centers for Medicare & Medicaid Services from quarter 1 of 1991 through quarter 2 of 2010. Average reimbursement per prescription was calculated each quarter as a proxy for drug price. RESULTS: The total number of prescriptions for the studied anti-asthma medications rose from 8.9 million in 1991 to 15.6 million in 2009, peaking at 20.8 million in 2005, the year before Medicare and Medicaid dual-eligible beneficiaries were moved to Medicare Part D. From 1991 to 2009, Medicaid spending on anti-asthma medications overall rose from $180.7 million to $1.3 billion, and spending on inhaled corticosteroid/long-acting beta-agonist combinations rose from $52.8 million in 2001-their first year on the market-to $411.7 million in 2009. The average price per prescription has risen in all the anti-asthma drug classes: overall, spending per prescription has increased 4-fold between 1991 and 2009, significantly faster than the consumer price index (57.5%) over the same period. In quarter 2 of 2010, Medicaid spent more on the combination medication fluticasone-salmeterol-$60 million-than on any other anti-asthma medication. CONCLUSION: Anti-asthma medications are a major and growing expense for state Medicaid programs and can be expected to be the same for Medicare Part D in the future. Increased disease prevalence has in part contributed to the rise in pharmacotherapy cost. Nevertheless, drug therapy is crucial for managing asthma and asthma exacerbations. PMID- 25126348 TI - The economic impact of delaying 5-alpha reductase inhibitor therapy in men receiving treatment for symptomatic benign prostatic hyperplasia. AB - BACKGROUND: Pharmacologic treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia often includes alpha-blockers and 5-alpha reductase inhibitors. Many clinicians use alpha-blockers for rapid symptom control, later adding 5-alpha reductase inhibitors to modify long-term disease progression. Delaying the addition of these medications has been shown to result in reduced clinical outcomes. The economic impact of this practice has not been widely studied or reported to date. OBJECTIVE: The objective of this study was to assess the economic impact of delaying initiation of concomitant 5-alpha reductase inhibitor therapy (>=30 days) in patients receiving alpha-blockers for lower urinary tract symptoms. METHODS: Using 2 nationally representative databases (Integrated Health Care Information Solutions and PharMetrics), 2 retrospective analyses were conducted involving 2636 and 4260 men, respectively, aged >=50 years treated for benign prostatic hyperplasia between 2000 and 2007. Economic outcomes (ie, the cost of therapy and the use of healthcare resources) were compared for adding 5-alpha reductase inhibitor therapy early (within <30 days of initiating an alpha-blocker) versus delaying these medications (>=30 days after initiating an alpha-blocker). RESULTS: In the Integrated Health Care Information Solutions analysis, patients in the early add-on therapy group (n = 1572) had lower benign prostatic hyperplasia-related medical costs in the posttreatment period than those in the delayed-therapy group (n = 1064), $349 versus $618 (P <.0001). Similar trends were seen in the PharMetrics analysis-the medical costs in the early add-on therapy group (n = 2604) and delayed group (n = 1656) were $344 versus $449, respectively (P <.001). Pharmacy costs were $1068 for the early-treatment cohort and $989 for the delayed-treatment cohort for the Integrated Health Care Information Solutions database, yielding total costs of $1417 and $1606, respectively, for a $189 savings per patient over the initial year of treatment (P <.0001). In the PharMetrics analysis, pharmacy costs were $1391 for the early-treatment cohort and $1237 for the delayed-treatment cohort, resulting in total cost of $1735 and $1686, respectively, yielding $59 in additional costs per patient annually for those treated early (P = .8645). CONCLUSION: These results suggest that patients receiving 5-alpha reductase inhibitor therapy within 30 days after initiating alpha-blocker treatment have lower benign prostatic hyperplasia-related medical costs than those who start combination treatment later. The increase in pharmacy costs associated with early initiation of 5-alpha reductase inhibitor therapy resulted in total costs that were similar or significantly lower than those of delayed combination users. PMID- 25126349 TI - From a to z: medication cost-management strategies for disproportionate share hospitals. AB - BACKGROUND: Harris County Hospital District, Houston, TX, is a publicly funded hospital system that provides care to residents of Harris County with a need based payment system. The Harris County Hospital District pharmacy department, with a drug budget of more than $75 million in fiscal year 2010, utilizes a closed formulary system that is managed by the Formulary Management and Pharmacoeconomics Service, along with the medical staff. This service is comprised of clinical pharmacists whose goal is to provide a comprehensive, safe, and cost-effective formulary. OBJECTIVE: To describe the unique formulary management process at a county hospital system and what makes this process cost effective, which may benefit pharmacy departments in institutions serving an indigent patient population. SUMMARY: The Harris County Hospital District drug formulary is overseen by the Pharmacy & Therapeutics committee, which is supported by 5 therapeutic subcommittees, including antimicrobials, cardiovascular, general formulary, central nervous system, and oncology. The Pharmacy & Therapeutics Committee consists of a medical staff committee that is supported by clinical pharmacists, who serve as the facilitators of these 5 subcommittees. Their responsibilities include the provision of drug information for formulary decisions, providing parameters to govern the use of certain medications, communicating changes to the formulary, conducting class reviews and medication utilization evaluations, coordinating annual pharmaceutical bids, reviewing and writing medication use policies and procedures, facilitating the use of cost-effective medications, and monitoring the use of medications in the hospital system. CONCLUSION: The processes incorporated by Harris County Hospital District in its formulary management are cost-effective and may be beneficial to other pharmacy departments, especially those institutions that serve an indigent patient population and are interested in cost-effective management strategies. PMID- 25126350 TI - Moving Beyond Medicare's ACOs to Accountable Care. PMID- 25126351 TI - The business case for payer support of a community-based health information exchange: a humana pilot evaluating its effectiveness in cost control for plan members seeking emergency department care. AB - BACKGROUND: As emergency department utilization continues to increase, health plans must limit their cost exposure, which may be driven by duplicate testing and a lack of medical history at the point of care. Based on previous studies, health information exchanges (HIEs) can potentially provide health plans with the ability to address this need. OBJECTIVE: To assess the effectiveness of a community-based HIE in controlling plan costs arising from emergency department care for a health plan's members. Albert Tzeel. METHODS: The study design was observational, with an eligible population (N = 1482) of fully insured plan members who sought emergency department care on at least 2 occasions during the study period, from December 2008 through March 2010. Cost and utilization data, obtained from member claims, were matched to a list of persons utilizing the emergency department where HIE querying could have occurred. Eligible members underwent propensity score matching to create a test group (N = 326) in which the HIE database was queried in all emergency department visits, and a control group (N = 325) in which the HIE database was not queried in any emergency department visit. RESULTS: Post-propensity matching analysis showed that the test group achieved an average savings of $29 per emergency department visit compared with the control group. Decreased utilization of imaging procedures and diagnostic tests drove this cost-savings. CONCLUSIONS: When clinicians utilize HIE in the care of patients who present to the emergency department, the costs borne by a health plan providing coverage for these patients decrease. Although many factors can play a role in this finding, it is likely that HIEs obviate unnecessary service utilization through provision of historical medical information regarding specific patients at the point of care. PMID- 25126353 TI - Managing utilization by exception. PMID- 25126352 TI - Modeling costs and outcomes associated with a treatment algorithm for problem bleeding episodes in patients with severe hemophilia a and high-titer inhibitors. AB - BACKGROUND: No evidence-based treatment guidelines are currently available for the treatment of problem bleedings in patients with hemophilia who develop clotting factor inhibitors. A treatment algorithm was developed previously to help providers optimize the approach to the treatment of this patient population. The algorithm provides the specific intervals between treatments; however, it does not specify dosing recommendations and does not offer insights into the likelihood of outcome improvements at each time interval. OBJECTIVE: To develop a model to analyze the impact on patient outcomes and costs of adhering to a current treatment algorithm for the 2 available clotting therapies to treat bleeding episodes in patients with hemophilia who develop clotting factor inhibitors. METHODS: A simulation model was developed using a modified Delphi method approach based on a consensus opinion of an expert panel. The model was used to analyze the impact of following the available treatment algorithm on patient outcomes and costs. Treatment patterns and the likelihood of a resolved bleeding episode associated with following the treatment algorithm (ie, adherence) were compared with not following the algorithm (ie, nonadherence). This model assumed 2 scenarios in which treatment was initiated with each of the 2 bypassing agents currently available, and clinical and economic outcomes were mapped for adhering to and not adhering to the consensus treatment algorithm. RESULTS: The simulation model shows that adhering to the treatment algorithm would result in 74.4% of patients improving at 72 hours compared with only 56.7% of patients when not adhering to the algorithm. According to this model, regardless of the bypassing agent used at initiation, adherence to the treatment algorithm would result in fewer patients requiring combined sequential therapy with the 2 bypassing agents for 3 days. In addition, using this analytic model, reducing the percentage of patients with hemophilia who required combined sequential therapy by 17.6% resulted in an average cost-savings of $16,305 per patient. CONCLUSION: Adherence to an algorithm in which treatment is altered at regular intervals based on a patient's clinical response has the potential to improve patient outcomes and reduce the number of nonresponsive patients requiring sequential therapy in patients with hemophilia who have clotting factor inhibitors and are experiencing problem bleeding episodes. >Adherence to the algorithm would also result in reduced costs to patients and payers. PMID- 25126354 TI - Anticoagulation Bridging Therapy Patterns in Patients Undergoing Total Hip or Total Knee Replacement in a US Health Plan: Real-World Observations and Implications. AB - BACKGROUND: The necessity for anticoagulant bridging therapy after joint replacement surgery is widely understood, but treatment administration patterns in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) or total knee replacement (TKR) surgery during the hospital stay have yet to be examined. OBJECTIVE: To investigate anticoagulation thromboprophylaxis patterns, especially the use of anticoagulant bridging therapy and/or nonbridged treatment strategies, in patients undergoing THR/TKR surgery. METHODS: This retrospective study was based on a large hospital database linked with outpatient claims from 2005 through 2007. The study population included 1770 patients who were admitted for either THR or TKR surgery and were aged >=18 years on the date of the surgery, defined as the index date. Patients were required to have commercial insurance or Medicare coverage and be continuously enrolled in their health plan for at least 180 days before and 90 days after the index date. The data were analyzed retrospectively for risk-adjusted postsurgery VTE and major bleeding events among patients receiving anticoagulation thromboprophylaxis. Patterns of anticoagulant bridging therapy use were also assessed. A risk adjustment was performed using propensity score matching. RESULTS: Of 1770 eligible patients, 1551 (88%) received anticoagulant VTE prophylaxis; 264 (15%) received combination low-molecular-weight heparin and warfarin. Of these, 105 (40%) patients were switched between the 2 monotherapies, and 159 (60%) received bridged (overlapping) prophylaxis. The overall rates of VTE and bleeding events were significantly lower with bridged therapy than with nonbridged therapy (5.8% vs 18.4%, respectively, for VTE, P <.02; 2.3% vs 4.60% for major bleeding, P = .41; 1.15% vs 8.05% for minor bleeding, P <.03). CONCLUSION: Although existing guidelines recommend anticoagulant bridging therapy after THR or TKR surgery, the limited data regarding anticoagulant bridging practice patterns suggest that patients who undergo such surgery do not receive adequate anticoagulant thromboprophylaxis immediately after discharge. Our findings suggest that increased use of bridging therapy after THR or TKR surgery may help improve postsurgery patient outcomes by reducing VTE and bleeding rates. PMID- 25126355 TI - Obesity in the workplace: impact on cardiovascular disease, cost, and utilization of care. AB - BACKGROUND: In forecasting the future of cardiovascular disease (CVD), the American Heart Association calls for preventive strategies with particular attention to obesity. The association between obesity and CVD, including coronary artery disease (CAD) and diabetes, is well established. The rising prevalence of obesity in the workforce may have additional implications for employers and employees besides the demonstrated effects on absenteeism and workers' compensation. OBJECTIVE: This study was undertaken to determine the impact of population obesity on care utilization and cost of cardiovascular conditions such as hypertension, CAD, and cerebrovascular disease (or stroke) in a large US population of employees engaged in a major corporate wellness program. STUDY SAMPLE: Using data from a single large industrial employer across 29 geographically distinct worksites in the United States, 179,708 episodes of care from 2004 to 2007 for 10,853 employees were included. METHODS: The population based economic impact of obesity was calculated on the basis of the frequency of episodes of care per 1000 employees and on the amount eligible for payment per episode of care in US dollars. Data were obtained from a wellness program databases, episode of illness inventories, and pharmacy and medical claims. High and low prevalence rates of obesity, by obesity quartile, were used to create linear mixed models to examine associations with disease outcomes, while controlling for correlation within each worksite. RESULTS: Worksites with a high rate of obesity (ie, in the fourth quartile) had 348.4 more episodes of care of any kind per 1000 employees (P <.001), 38.6 more hypertension episodes of care per 1000 employees (P <.001), and 2.5 more cerebrovascular disease episodes of care per 1000 employees (P = .017) compared with worksites in the lower 3 quartiles. A worksite in the fourth obesity rate quartile had $223 greater cost per any kind of episode (P <.001), $169 greater cost per hypertension episode (P = .003), and $1620 more per CAD episode (P = .005) compared with worksites in the lower 3 quartiles. The overall economic impact per 1000 employees was calculated by combining episode frequency and eligible amount for payment per episode. For sites in the lower 3 quartiles of obesity, the eligible amount per 1000 employees for any kind of care was $4.01 million. However, for sites in the highest obesity quartile, the eligible amount for payment per 1000 employees was $5.26 million. This translates into $1250 greater cost per employee. Similar calculations were used to evaluate the effect of obesity on the amount eligible for payment per employee for hypertension, CAD, and cerebrovascular disease episodes, with an estimated $69, $89, and $8 greater cost, respectively, per employee. CONCLUSION: Worksites with greater obesity prevalence rates were associated with numerically more frequent and more expensive episodes of care than worksites with low obesity prevalence. PMID- 25126356 TI - A call to action: responding to the future forecasting of cardiovascular disease in america. AB - BACKGROUND: Cardiovascular disease (CVD) continues to be a leading cost driver for payers in the United States.1 The American Heart Association estimates that more than 75 million individuals nationwide have some form of CVD. Individuals aged 20 to 45 years are developing CVD at higher rates than ever before. OBJECTIVES: To discuss the alarming increase in the rate of CVD in young adults (aged 18-45 years) previously only seen in older adults (aged >=65 years) and describe the 5 primary risk factors (smoking, obesity, hypertension, diabetes, and dyslipidemia) that contribute to this new trend in the working-age population. DISCUSSION: Using Medical Expenditure Panel Survey data, this article outlines the increased prevalence of the 3 primary components of CVD-stroke, heart failure, and myocardial infarction-in younger adults and the cost impact on payers and on US society. The examples provided in this article highlight the need for increased efforts by all healthcare stakeholders, and by payers in particular, to develop prevention strategies for CVD risk factors targeted at young adults to curb the alarming rise in CVD among this age-group. CONCLUSION: This article provides compelling evidence for the need to institute prevention measures to curb the growing prevalence of CVD risk factors among younger adults in the United States. PMID- 25126357 TI - Atypical antipsychotics and metabolic syndrome in patients with schizophrenia: risk factors, monitoring, and healthcare implications. AB - BACKGROUND: Metabolic syndrome is a leading cause of morbidity and mortality in patients with schizophrenia, with a prevalence rate double that of nonpsychiatric populations. Given the amount of evidence suggesting a link between atypical antipsychotic medications and metabolic syndrome, several agencies have recommended regular clinical monitoring of weight, symptoms of hyperglycemia, and glucose in chronically medicated patients with schizophrenia. OBJECTIVES: To summarize the current literature on atypical antipsychotic-induced metabolic syndrome in patients with schizophrenia, outline some of the molecular mechanisms behind this syndrome, identify demographic and disease-related risk factors, and describe cost-effective methods for surveillance. DISCUSSION: The differential prevalence of metabolic syndrome associated with various atypical antipsychotic medications has been evidenced across numerous studies, with higher effects seen for certain antipsychotic medications on weight gain, waist circumference, fasting triglyceride level, and glucose levels. Given the association of these symptoms, all atypical antipsychotic medications currently include a warning about the risk of hyperglycemia and diabetes, as well as suggestions for regular monitoring. Despite this, very little data are available to support adherence to these monitoring recommendations. Lack of awareness and resources, diffusion of responsibility, policy implementation, and organizational structure have all been implicated. CONCLUSION: The treatment of schizophrenia involves a balance in terms of risks and benefits. Failing to treat because of risk for complications from metabolic syndrome may place the patient at a higher risk for more serious health outcomes. Supporting programs aimed at increasing monitoring of simple laboratory and clinical measures associated with metabolic syndrome may decrease important risk factors, improve patients' quality of life, and reduce healthcare costs. PMID- 25126359 TI - Lipid management in patients with type 2 diabetes. AB - BACKGROUND: Diabetes is correlated with a high risk for cardiovascular disease (CVD). The management of diabetic dyslipidemia, a well-recognized and modifiable risk factor, is a key element in the multifactorial approach to preventing CVD in patients with type 2 diabetes. Diabetic dyslipidemia is characterized by elevated triglyceride levels, decreased high-density lipoprotein cholesterol levels, and elevated low-density lipoprotein cholesterol (LDL-C) levels. OBJECTIVES: To describe the effective approach to the management of dyslipidemia in patients with diabetes to allow providers and payers to become familiar with the treatment goals for all the components of lipoproteins, to correctly initiate appropriate lipid-lowering medications based on treatment goals and lipid-lowering capability, and to apply the data presented in lipid clinical trials to the treatment of patients with diabetes. SUMMARY: Diabetes is associated with a 2- to 4-fold increase in risk for CVD. The risk factors for coronary artery disease (CAD) include hypertension, dyslipidemia, obesity, and smoking. Therefore, prioritizing and managing diabetic patients with CVD risk factors is vital. CONCLUSION: LDL-C appears to have the greatest role in premature and early atherosclerosis and the development of CAD and must be treated as aggressively as hyperglycemia to reduce CAD risk. Becoming familiar with lipid treatment goals and the many therapies available today can help providers and payers implement the appropriate approach to managing diabetic dyslipidemia risk factors and reduce the burden of this disease. PMID- 25126360 TI - From asheville to hickory: transforming our "sick care" system into a true "health care" model. PMID- 25126361 TI - The hickory project: controlling healthcare costs and improving outcomes for diabetes using the asheville project model. AB - BACKGROUND: The results of the Asheville Project have shown the success of a community-based, chronic disease management model in improving clinical outcomes in patients with chronic disease while reducing annual costs of care per participant. The question arose whether other programs using a similar management model and implemented in other communities could replicate the success of the Asheville Project in improving clinical outcomes and reducing costs for patients with a chronic disease. OBJECTIVE: To assess the long-term clinical and financial outcomes of a chronic care management model for patients with diabetes, using the Asheville care management model that was successful in the management of several chronic diseases. STUDY DESIGN: Longitudinal, 3-year (2007-2009), quasi experimental, multisite, pre-/postenrollment study. METHODS: Self-insured health plan members with diabetes agreed to meet on a regular basis (ie, an average of every 3 months) with a healthcare professional. Participants received reduced copayments on diabetes-related medications and supplies as an incentive for participating in the study. Providers utilized a web-based electronic medical record system that provided updated medical and prescription data and highlighted gaps in care based on national standards. Program providers included community pharmacists, population health management company pharmacists, and nurses at on site clinics, trained in use of evidence-based guidelines of care. Providers assessed patients' medications, knowledge level, and lifestyle; provided patient education and goal setting; and referred patients for physician follow-up and recommendations to physicians. The majority of the encounters were face-to-face. RESULTS: The study included 95 plan members in the clinical cohort participating for 1 year or more, and 54 members in the financial cohort who have been participating in the program for 3 years. At the end of 3 years, the percentages of those achieving guideline goals increased from baseline to the latest follow up included, respectively, reaching target hemoglobin A1c levels, 38% to 53%; low density lipoprotein cholesterol, 46% to 67%; systolic blood pressure (BP), 55% to 72%; diastolic BP, 60% to 71%; annual eye examination, 37% to 61%; and self testing blood glucose, 79% to 97%. Total healthcare costs decreased by an average of $2704 per participant per year. The program's return on investment was $4.89 to every $1 spent (including program costs). CONCLUSION: The Hickory Project shows that it is possible to produce sustained improvements in clinical outcomes and reductions in healthcare costs for patients with diabetes using a chronic care model that provides frequent patient follow-up, a focus on appropriate medication therapy, adherence to clinical practice guidelines, and a reduction in prescription copayments for antidiabetes medications as an incentive for patients to participate in the program. PMID- 25126358 TI - Current therapies and emerging drugs in the pipeline for type 2 diabetes. AB - BACKGROUND: Diabetes is a global epidemic that affects 347 million people worldwide and 25.8 million adults in the United States. In 2007, the total estimated cost associated with diabetes in the United States in 2007 was $174 billion. In 2009, $16.9 billion was spent on drugs for diabetes. The global sales of diabetes pharmaceuticals totaled $35 billion in 2010, and these are expected to rise to $48 billion by 2015. Despite such considerable expenditures, in 2000 only 36% of patients with type 2 diabetes in the United States achieved glycemic control, defined as hemoglobin A1c <7%. OBJECTIVE: To review some of the most important drug classes currently in development for the treatment of type 2 diabetes. DISCUSSION: Despite the 13 classes of antidiabetes medications currently approved by the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes, the majority of patients with this chronic disease do not achieve appropriate glycemic control with these medications. Many new drug classes currently in development for type 2 diabetes appear promising in early stages of development, and some of them represent novel approaches to treatment, with new mechanisms of action and a low potential for hypoglycemia. Among these promising pharmacotherapies are agents that target the kidney, liver, and pancreas as a significant focus of treatment in type 2 diabetes. These investigational agents may potentially offer new approaches to controlling glucose levels and improve outcomes in patients with diabetes. This article focuses on several new classes, including the sodium-glucose cotransporter-2 inhibitors (which are furthest along in development); 11beta-hydroxysteroid dehydrogenase (some of which are now in phase 2 trials); glycogen phosphorylase inhibitors; glucokinase activators; G protein-coupled receptor 119 agonists; protein tyrosine phosphatase 1B inhibitors; and glucagon-receptor antagonists. CONCLUSION: Despite the abundance of FDA-approved therapeutic options for type 2 diabetes, the majority of American patients with diabetes are not achieving appropriate glycemic control. The development of new options with new mechanisms of action may potentially help improve outcomes and reduce the clinical and cost burden of this condition. PMID- 25126363 TI - Adapting to market changes: beyond healthcare reform. PMID- 25126362 TI - Health Resource Utilization and Direct Costs Associated with Angina for Patients with Coronary Artery Disease in a US Managed Care Setting. AB - BACKGROUND: Angina is often a first symptom of coronary artery disease (CAD); however, the specific burden of illness for patients with CAD-associated angina in managed care has not been reported. OBJECTIVE: To determine the clinical and cost burden of illness for patients with CAD-associated angina in a managed care environment. STUDY DESIGN: A retrospective database analysis in a nationwide commercial managed care plan. METHODS: This study included patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic or procedure codes for CAD between July 1, 2004, and June 30, 2006, who had data available for the period 6 months before and 12 months after the index date. The primary analyses for patients classified as having CAD with angina were based on a 3-algorithm patient-identification model (combined positive predictive value of 89%, 95% confidence interval, 0.79-0.95). Utilization measures for the 12-month postindex period, annual CAD-related direct costs, and total all-cause costs (ie, medical plus pharmacy) were determined. A generalized linear model was used to compare CAD-related costs and overall costs. RESULTS: Of the 246,227 patients with CAD, the 3-algorithm model assigned 230,919 patients (93.8%) to the CAD-without-angina cohort and 15,308 (6.2%) to the CAD with-angina cohort. Patients with angina were more likely than patients without angina to be hospitalized (41% vs 11%, respectively; P <.001), to visit the emergency department (34% vs 12%, respectively; P <.001), to have office visits (94% vs 79%, respectively; P <.001), and to have more revascularization procedures (35% vs 8%, respectively; P <.001). Average CAD-related inpatient costs were $9536 versus $2169, and pharmacy costs were $1499 versus $891, for patients with and without angina, respectively. Total average CAD-related medical and pharmacy costs for patients with angina were $14,851 versus $4449 for patients with CAD without angina, and the average all-cause per-patient cost was $28,590 versus $14,334, respectively. CONCLUSION: Based on these results, US patients with CAD plus angina in a managed care setting use significantly more healthcare services and incur higher costs than patients who have CAD without angina. Revascularization procedures are a major driver of these increased costs for those with CAD and angina. PMID- 25126365 TI - The era of personalized medicine in oncology: novel biomarkers ushering in new approaches to cancer therapy. PMID- 25126364 TI - Review of strategies to enhance outcomes for patients with type 2 diabetes: payers' perspective. AB - BACKGROUND: Diabetes and its clinical consequences exact a great toll on patients and on society in terms of its effects on morbidity and mortality and its staggering economic impact. OBJECTIVE: To review various programs and strategies that aim at enhancing adherence to antihyperglycemic therapy and suggest the best approach to improving patient outcomes and reducing healthcare costs. DISCUSSION: Treatment goals for patients with diabetes have been defined, and multiple safe and effective medications are available. Nevertheless, the majority of patients with diabetes fail to achieve treatment goals, because of difficulty with adherence to medication regimens and lifestyle modifications, and because of economic barriers. This article discusses various initiatives developed to improve patient outcomes, including consumer-driven health plans and wellness and prevention programs. Furthermore, economic incentives to patients, such as value based insurance design, may increase adherence; nevertheless, evidence suggests that such programs alone provide only modest gains. Primary providers in disease management programs can include nurses, case managers, or pharmacists. Supportive interventions across several modalities have been shown to be effective. CONCLUSION: An approach that uses a combination of strategies designed to impact patients' health-related behaviors across a variety of modalities may help to improve outcomes and reduce costs. Additional novel, innovative interdisciplinary initiatives are necessary to effect meaningful change that can facilitate improved health outcomes for patients with diabetes and maximize cost effectiveness approaches for payers. PMID- 25126366 TI - Building Your Automated Bundled Payment for an Episode-of-Care Initiative. PMID- 25126367 TI - Impact of Treatment by NCQA-Certified Physicians on Diabetes-Related Outcomes. AB - BACKGROUND: The National Committee for Quality Assurance supports high-quality care for patients through the Diabetes Recognition Program (DRP). The DRP recognizes physicians and practices that are providing high-quality diabetes care as determined by 10 key measures. OBJECTIVE: To examine the impact of treatment by DRP-certified physicians compared with non-DRP-certified physicians on patient outcomes. METHODS: This retrospective claims analysis was conducted from January 1, 2007, through November 30, 2007, using a large US database of approximately 14 million commercially insured members. Physicians with DRP certification (N = 1188) were identified and matched 1:1 to physicians without DRP certification based on physician specialty, location (state) of practice, size of potential patient population, and number of patients with type 2 diabetes treated by the physician. Patients were included if they had type 2 diabetes and had been treated by a physician in the DRP group (N = 3836) or in the comparison group (N = 4175). Primary outcomes were medication use, medical resource utilization, and expenditures. Per-patient per-year (PPPY) medical and pharmacy utilization measures were analyzed using Poisson regression; PPPY expenditures were estimated using a generalized linear model with gamma distribution. RESULTS: Multivariate analysis showed that patients treated by DRP-certified physicians had more postindex diabetes-related office visits (mean PPPY, 4.69 vs 4.44, respectively; P <.001) and outpatient visits (mean PPPY, 0.93 vs 0.85, respectively; P <.001) than patients treated by non-DRP-certified physicians, but fewer emergency department visits (mean PPPY, 0.04 vs 0.07, respectively; P <.001) and inpatient visits (mean PPPY, 0.08 vs 0.10, respectively; P = .02). Prescribing rates for oral antihyperglycemic drugs and statins were higher among DRP-certified physicians than non-DRP-certified physicians. Total diabetes-related healthcare expenditures were lower for patients with type 2 diabetes managed by DRP certified physicians compared with those managed by non-DRP-certified physicians (mean PPPY, $3424 vs $4097, respectively; P = .03). CONCLUSION: Significant differences in oral antihyperglycemic and statin drug use, and diabetes-related emergency department and inpatient visits and expenditures, were observed in this study between DRP-certified and non-DRP-certified physicians, showing overall improved outcomes for patients managed by DRP-certified physicians. PMID- 25126368 TI - Are ACOs the Answer to High-Value Healthcare? AB - BACKGROUND: The Patient Protection and Affordable Care Act required the Secretary of the Department of Health and Human Services to establish the Medicare Shared Savings Program (MSSP) by January 1, 2012. The MSSP is intended to encourage physicians, hospitals, and other providers and suppliers to form accountable care organizations (ACOs) to provide cost-effective, coordinated care to Medicare beneficiaries. Under the MSSP, ACOs can qualify for additional payments by meeting specific savings benchmarks and quality measures. OBJECTIVES: To review the anticipated changes in the role and responsibilities of ACOs and to evaluate the challenges and opportunities that various healthcare stakeholders, including patients, providers, and payers, will encounter with the launching of the new MSSP. DISCUSSION: ACOs assume responsibility for overall care, cost, and quality of patient care. The MSSP will provide ACOs additional payments for meeting cost savings and quality benchmarks. The extra savings will be shared with participating providers based on different risk-sharing options. As the MSSP and new ACOs launch, stakeholders will be impacted differently. This article is based, in part, on responses of approximately 100 payers to a survey conducted in June 2011 by Xcenda. Each stakeholder group, including providers, payers, patients, and manufacturers, must monitor the reactions and relationships between all players in the care continuum. Providers will have to achieve a greater level of coordination and collaboration than typically exists today. Government and commercial payers will have a role in determining how quickly they will adopt accountable care models. Patients are expected to become more engaged and participatory in their care to achieve optimal outcomes, and manufacturers will be required to prove the value of their products given the clinical value proposition embedded in accountable care models. CONCLUSION: Whether ACOs are the answer to providing higher-quality healthcare at lower costs remains unclear. All signs, however, point toward a systemic change in an effort to improve patient care and contain healthcare costs. It will be important for all healthcare stakeholders to understand the roles that ACOs will play in ensuring access to care and quality of care. PMID- 25126369 TI - Back to School: Quality Improvement through Academic Detailing. PMID- 25126371 TI - 2014: the year of the healthcare consumer. PMID- 25126370 TI - Sensitivity of medication use to formulary controls in medicare beneficiaries: a review of the literature. AB - BACKGROUND: Several studies have examined the impact of formulary management strategies on medication use in the elderly, but little has been done to synthesize the findings to determine whether the results show consistent trends. OBJECTIVE: To summarize the effects of formulary controls (ie, tiered copays, step edits, prior authorization, and generic substitution) on medication use in the Medicare population to inform future Medicare Part D and other coverage decisions. METHODS: This systematic review included research articles (found via PubMed, Google Scholar, and specific scientific journals) that evaluated the impact of drug coverage or cost-sharing on medication use in elderly (aged >=65 years) Medicare beneficiaries. The impact of drug coverage was assessed by comparing patients with some drug coverage to those with no drug coverage or by comparing varying levels of drug coverage (eg, full coverage vs $1000 coverage or capped benefits vs noncapped benefits). Articles that were published before 1995, were not original empirical research, were published in languages other than English, or focused on populations other than Medicare beneficiaries were excluded. All studies selected were classified as positive, negative, or neutral based on the significance of the relationship (P <.05 or as otherwise specified) between the formulary control mechanism and the medication use, and on the direction of that relationship. RESULTS: Included were a total of 47 research articles (published between 1995 and 2009) that evaluated the impact of drug coverage or cost-sharing on medication use in Medicare beneficiaries. Overall, 24 studies examined the impact of the level of drug coverage on medication use; of these, 96% (N = 23) supported the association between better drug coverage (ie, branded and generic vs generic-only coverage, capped benefit vs noncapped benefit, supplemental drug insurance vs no supplemental drug insurance) or having some drug coverage and enhanced medication use. Furthermore, 84% (N = 16) of the 19 studies that examined the effect of cost-sharing on medication use demonstrated that decreased cost-sharing was significantly associated with improved medication use. CONCLUSION: Current evidence from the literature suggests that restricting drug coverage or increasing out-of-pocket expenses for Medicare beneficiaries may lead to decreased medication use in the elderly, with all its potential implications. PMID- 25126372 TI - The economic burden of ischemic stroke and major hemorrhage in medicare beneficiaries with nonvalvular atrial fibrillation: a retrospective claims analysis. AB - BACKGROUND: Understanding the economic implications of oral anticoagulation therapy requires careful consideration of the risks and costs of stroke and major hemorrhage. The majority of patients with atrial fibrillation (AF) are aged >=65 years, so focusing on the Medicare population is reasonable when discussing the risk for stroke. OBJECTIVE: To examine the relative economic burden associated with stroke and major hemorrhage among Medicare beneficiaries who are newly diagnosed with nonvalvular atrial fibrillation (NVAF). METHODS: This study was a retrospective analysis of a 5% sample of Medicare claims data for patients with NVAF from 2006 to 2008. Patients with NVAF without any claims of AF during the 12 months before the first (index) claim for AF in 2007 (baseline period) were identified and were classified into 4 cohorts during a 12-month follow-up period after the index date. These cohorts included (1) no claims for ischemic stroke or major hemorrhage (without stroke or hemorrhage); (2) no claims for ischemic stroke and >=1 claims for major hemorrhage (hemorrhage only); (3) >=1 claims for ischemic stroke and no major hemorrhage claims (stroke only); and (4) >=1 claims each for ischemic stroke and for major hemorrhage (stroke and hemorrhage). The 1 year mean postindex total all-cause healthcare costs adjusted by the Centers for Medicare & Medicaid Services Hierarchical Condition Categories (HCC) score were compared among the study cohorts. RESULTS: Of the 9455 eligible patients included in this study, 3% (N = 261) of the patients had ischemic stroke claims only, 3% (N = 276) had hemorrhage claims only, and <1% (N = 13) had both during the follow up period. The unadjusted follow-up healthcare costs were $63,781 and $64,596 per patient for the ischemic stroke only and the hemorrhage only cohorts, respectively, compared with $35,474 per patient for those without hemorrhage or stroke claims. After adjustment for HCC risk score, the mean incremental costs for patients with stroke claims only and hemorrhage claims only, relative to those without stroke or hemorrhage claims, were $26,776 (95% confidence interval [CI], $20,785-$32,767; P <.001) and $26,168 (95% CI, $20,375-$31,961; P <.001), respectively. CONCLUSION: The economic burden of managing patients with NVAF who experience ischemic stroke and hemorrhage were similarly significant during the first year after a diagnosis of NVAF. The burden of major bleeding complications on patients, clinicians, and payers should not be overlooked, and these complications should be considered in conjunction with the cost-savings associated with ischemic stroke risk reduction in future cost-benefit evaluations of oral anticoagulation therapy. PMID- 25126373 TI - The health and economic effects of counterfeit drugs. AB - BACKGROUND: Counterfeit drugs comprise an increasing percentage of the US drug market and even a larger percentage in less developed countries. Counterfeit drugs involve both lifesaving and lifestyle drugs. OBJECTIVE: To review the health and economic consequences of counterfeit drugs on the US public and on the healthcare system as a whole. METHOD: This comprehensive review of the literature encompassed a search of MEDLINE/PubMed, Google Scholar, and ProQuest using the keywords "counterfeit drugs," "counterfeit medicines," "fake drugs," and "fake medicines." A search of the various FiercePharma daily newsletter series on the healthcare market was also conducted. In addition, the US Food and Drug Administration and the World Health Organization websites were reviewed for additional information. DISCUSSION: The issue of counterfeit drugs has been growing in importance in the United States, with the supply of these counterfeit drugs coming from all over the world. Innovation is important to economic growth and US competitiveness in the global marketplace, and intellectual property protections provide the ability for society to prosper from innovation. Especially important in terms of innovation in healthcare are the pharmaceutical and biopharmaceutical industries. In addition to taking income from consumers and drug companies, counterfeit drugs also pose health hazards to patients, including death. The case of bevacizumab (Avastin) is presented as one recent example. Internet pharmacies, which are often the source of counterfeit drugs, often falsely portray themselves as Canadian, to enhance their consumer acceptance. Adding to the problems are drug shortages, which facilitate access for counterfeits. A long and convoluted supply chain also facilitates counterfeits. In addition, the wholesale market involving numerous firms is a convenient target for counterfeit drugs. Trafficking in counterfeits can be extremely profitable; detection of counterfeits is difficult, and the penalties are modest. CONCLUSION: Counterfeit drugs pose a public health hazard, waste consumer income, and reduce the incentive to engage in research and development and innovation. Stronger state licensure supervision of drug suppliers would be helpful. Technological approaches, such as the Radio Frequency Identification devices, should also be considered. Finally, counterfeit drugs may raise concerns among consumers about safety and reduce patient medication adherence. PMID- 25126374 TI - Salsalate, an old, inexpensive drug with potential new indications: a review of the evidence from 3 recent studies. AB - BACKGROUND: Diabetes is a well-known growing epidemic, but prediabetes is increasing at an even greater rate. Lifestyle changes are effective tools to prevent the progression of prediabetes to diabetes, yet many people are unable to follow such changes. Salsalate has been suggested as a possible treatment for diabetes as early as 1876 and as recently as in a 2013 study. OBJECTIVE: To review the recently published evidence about the potential therapeutic benefits of the old drug salsalate for individuals who meet the criteria of having prediabetes. DISCUSSION: With the rising incidence of obesity and prediabetes, it has become prudent to look for more therapeutic options. Salsalate belongs to the salicylate drug class, which has been shown to inhibit I-kappaB kinase, thereby inhibiting the nuclear factor-kappaB (NF-kappaB) cascade and decreasing the production of inflammatory cytokines, as well as decreasing insulin resistance. Recent short-term clinical trials have shown that 3 g to 4.5 g of salicylate therapy daily has the ability to lower insulin resistance and to reduce the levels of glucose, triglycerides, and free fatty acid concentrations through regulation of the I-kappaB kinase beta/NF-kappaB pathway, with few if any side effects. However, the effectiveness of salsalate as a treatment option for prediabetes is largely unrecognized. This article summarizes the current evidence from 3 studies of salsalate therapy in the setting of the prediabetic population and presents the case for its use in this population. CONCLUSION: As shown in this review, salsalate therapy at the dose of 3 g to 4.5 g daily can lower insulin resistance and reduce the levels of glucose, triglycerides, and free fatty acid concentrations with minimal side effects. This inexpensive medication could be a useful option in the treatment of prediabetes. Larger clinical trials are needed, but the data are encouraging and should lay the foundation for further investigation and grant funding. PMID- 25126375 TI - Pharmacy management and health economics outcomes. AB - The following summaries highlight some of the key posters presented at the 26th Annual Meeting of the Academy of Managed Care Pharmacy (AMCP), April 1-4, 2014, in Tampa, FL, focusing on areas of interest for payers, employers, drug manufacturers, providers, and other healthcare stakeholders. PMID- 25126376 TI - Adipose-derived mesenchymal stromal/stem cells: An update on their phenotype in vivo and in vitro. AB - Adipose tissue is a rich, ubiquitous and easily accessible source for multipotent stromal/stem cells and has, therefore, several advantages compared to other sources of mesenchymal stromal/stem cells. Several studies have tried to identify the origin of the stromal/stem cell population within adipose tissue in situ. This is a complicated attempt because no marker has currently been described which unambiguously identifies native adipose-derived stromal/stem cells (ASCs). Isolated and cultured ASCs are a non-uniform preparation consisting of several subsets of stem and precursor cells. Cultured ASCs are characterized by their expression of a panel of markers (and the absence of others), whereas their in vitro phenotype is dynamic. Some markers were expressed de novo during culture, the expression of some markers is lost. For a long time, CD34 expression was solely used to characterize haematopoietic stem and progenitor cells, but now it has become evident that it is also a potential marker to identify an ASC subpopulation in situ and after a short culture time. Nevertheless, long-term cultured ASCs do not express CD34, perhaps due to the artificial environment. This review gives an update of the recently published data on the origin and phenotype of ASCs both in vivo and in vitro. In addition, the composition of ASCs (or their subpopulations) seems to vary between different laboratories and preparations. This heterogeneity of ASC preparations may result from different reasons. One of the main problems in comparing results from different laboratories is the lack of a standardized isolation and culture protocol for ASCs. Since many aspects of ASCs, such as the differential potential or the current use in clinical trials, are fully described in other recent reviews, this review further updates the more basic research issues concerning ASCs' subpopulations, heterogeneity and culture standardization. PMID- 25126377 TI - Periosteum derived stem cells for regenerative medicine proposals: Boosting current knowledge. AB - Periosteum is a thin fibrous layer that covers most bones. It resides in a dynamic mechanically loaded environment and provides a niche for pluripotent cells and a source for molecular factors that modulate cell behaviour. Elucidating periosteum regenerative potential has become a hot topic in orthopaedics. This review discusses the state of the art of osteochondral tissue engineering rested on periosteum derived progenitor cells (PDPCs) and suggests upcoming research directions. Periosteal cells isolation, characterization and migration in the site of injury, as well as their differentiation, are analysed. Moreover, the role of cell mechanosensing and its contribution to matrix organization, bone microarchitecture and bone stenght is examined. In this regard the role of periostin and its upregulation under mechanical stress in order to preserve PDPC survival and bone tissue integrity is contemplated. The review also summarized the role of the periosteum in the field of dentistry and maxillofacial reconstruction. The involvement of microRNAs in osteoblast differentiation and in endogenous tissue repair is explored as well. Finally the novel concept of a guided bone regeneration based on the use of periosteum itself as a smart material and the realization of constructs able to mimic the extracellular matrix features is talked out. Additionally, since periosteum can differentiate into insulin producing cells it could be a suitable source in allogenic transplantations. That innovative applications would take advantage from investigations aimed to assess PDPC immune privilege. PMID- 25126378 TI - Osteogenic potential: Comparison between bone marrow and adipose-derived mesenchymal stem cells. AB - Bone tissue engineering (BTE) is now a promising research issue to improve the drawbacks from traditional bone grafting procedure such as limited donor sources and possible complications. Stem cells are one of the major factors in BTE due to the capability of self renewal and multi-lineage differentiation. Unlike embryonic stem cells, which are more controversial in ethical problem, adult mesenchymal stem cells are considered to be a more appropriate cell source for BTE. Bone marrow mesenchymal stem cells (BMSCs) are the earliest-discovered and well-known stem cell source using in BTE. However, the low stem cell yield requiring long expansion time in vitro, pain and possible morbidities during bone marrow aspiration and poor proliferation and osteogenic ability at old age impede its' clinical application. Afterwards, a new stem cell source coming from adipose tissue, so-called adipose-derived stem cells (ASCs), is found to be more suitable in clinical application because of high stem cells yield from lipoaspirates, faster cell proliferation and less discomfort and morbidities during harvesting procedure. However, the osteogenic capacity of ASCs is now still debated because most papers described the inferior osteogenesis of ASCs than BMSCs. A better understanding of the osteogenic differences between ASCs and BMSCs is crucial for future selection of cells in clinical application for BTE. In this review, we describe the commonality and difference between BMSCs and ASCs by cell yield, cell surface markers and multiple-differentiation potential. Then we compare the osteogenic capacity in vitro and bone regeneration ability in vivo between BMSCs and ASCs based on the literatures which utilized both BMSCs and ASCs simultaneously in their articles. The outcome indicated both BMSCs and ASCs exhibited the osteogenic ability to a certain extent both in-vitro and in-vivo. However, most in-vitro study papers verified the inferior osteogenesis of ASCs; conversely, in-vivo research reviews revealed more controversies in this issue. We expect the new researchers can have a quick understanding of the progress in this filed and design a more comprehensive research based on this review. PMID- 25126379 TI - Mesenchymal stem cells: Potential role in corneal wound repair and transplantation. AB - Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain problematic. Mesenchymal stem cells (MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In addition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoimmune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation. PMID- 25126380 TI - Sox2, a key factor in the regulation of pluripotency and neural differentiation. AB - Sex determining region Y-box 2 (Sox2), a member of the SoxB1 transcription factor family, is an important transcriptional regulator in pluripotent stem cells (PSCs). Together with octamer-binding transcription factor 4 and Nanog, they co operatively control gene expression in PSCs and maintain their pluripotency. Furthermore, Sox2 plays an essential role in somatic cell reprogramming, reversing the epigenetic configuration of differentiated cells back to a pluripotent embryonic state. In addition to its role in regulation of pluripotency, Sox2 is also a critical factor for directing the differentiation of PSCs to neural progenitors and for maintaining the properties of neural progenitor stem cells. Here, we review recent findings concerning the involvement of Sox2 in pluripotency, somatic cell reprogramming and neural differentiation as well as the molecular mechanisms underlying these roles. PMID- 25126381 TI - Adipose-derived stem cells: Implications in tissue regeneration. AB - Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differentiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs damaged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration. PMID- 25126383 TI - Mesenchymal stem cells as a potent cell source for articular cartilage regeneration. AB - Since articular cartilage possesses only a weak capacity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is associated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechanical properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical procedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morphological features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells (MSCs) to be an appropriate cellular material for articular cartilage repair. These cells were originally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic differentiation is an inherent property of MSCs noticed at the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative properties. Moreover, these cells possess a considerable immunomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review. PMID- 25126385 TI - Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells? AB - In cell therapy protocols, many tissues were proposed as a source of mesenchymal stem cells (MSC) isolation. So far, bone marrow (BM) has been presented as the main source of MSC despite the invasive isolation procedure related to this source. During the last years, the umbilical cord (UC) matrix was cited in different studies as a reliable source from which long term ex vivo proliferating fibroblasts were isolated but with contradictory data about their immunophenotype, gene expression profile, and differentiation potential. Hence, an interesting question emerged: Are cells isolated from cord matrix (UC-MSC) different from other MSCs? In this review, we will summarize different studies that isolated and characterized UC-MSC. Considering BM-MSC as gold standard, we will discuss if UC-MSC fulfill different criteria that define MSC, and what remain to be done in this issue. PMID- 25126384 TI - Endothelial progenitor cells in cardiovascular diseases. AB - Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells (EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vasculogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk factors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardiovascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evaluate the challenges facing EPC research and how these may be overcome. PMID- 25126386 TI - The 2-Methoxy Group Orientation Regulates the Redox Potential Difference between the Primary (QA) and Secondary (QB) Quinones of Type II Bacterial Photosynthetic Reaction Centers. AB - Recent studies have shown that only quinones with a 2-methoxy group can act simultaneously as the primary (QA) and secondary (QB) electron acceptors in photosynthetic reaction centers from purple bacteria such as Rb. sphaeroides. 13C HYSCORE measurements of the 2-methoxy group in the semiquinone states, SQA and SQB, were compared with DFT calculations of the 13C hyperfine couplings as a function of the 2-methoxy dihedral angle. X-ray structure comparisons support 2 methoxy dihedral angle assignments corresponding to a redox potential gap (DeltaEm) between QA and QB of 175-193 mV. A model having a methyl group substituted for the 2-methoxy group exhibits no electron affinity difference. This is consistent with the failure of a 2-methyl ubiquinone analogue to function as QB in mutant reaction centers with a DeltaEm of ~160-195 mV. The conclusion reached is that the 2-methoxy group is the principal determinant of electron transfer from QA to QB in type II photosynthetic reaction centers with ubiquinone serving as both acceptor quinones. PMID- 25126382 TI - Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics. AB - Multiple myeloma is a hematological malignancy in which clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic lesions due to increased osteoclast (OC) activity and suppressed osteoblast (OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells (MSCs) play a critical role in multiple myeloma pathophysiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of myeloma bone disease (MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients (pMSCs) and their healthy counterparts (dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibitory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and activity at various levels (i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncoupling ephrinB2-EphB4 signaling, and through augmented production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents (at preclinical or clinical stage) targeting those signaling pathways is commented. PMID- 25126387 TI - FTIR Spectroscopy Revealing Light-Dependent Refolding of the Conserved Tongue Region of Bacteriophytochrome. AB - Bacteriophytochromes (BphPs) constitute a class of photosensory proteins that toggle between Pr and Pfr functional states through absorption of red and far-red light. The photosensory core of BphPs is composed of PAS, GAF, and PHY domains. Here, we apply FTIR spectroscopy to investigate changes in the secondary structure of Rhodopseudomonas palustris BphP2 (RpBphP2) upon Pr to Pfr photoconversion. Our results indicate conversion from a beta-sheet to an alpha helical element in the so-called tongue region of the PHY domain, consistent with recent X-ray structures of Deinococcus radiodurans DrBphP in dark and light states (Takala H.; et al. Nature2014, 5, 245-248). A conserved Asp in the GAF domain that noncovalently connects with the PHY domain and a conserved Pro in the tongue region of the PHY domain are essential for the beta-sheet-to-alpha-helix conversion. PMID- 25126388 TI - Biological Targeting of Plasmonic Nanoparticles Improves Cellular Imaging via the Enhanced Scattering in the Aggregates Formed. AB - Gold nanoparticles (AuNPs) demonstrate great promise in biomedical applications due to their plasmonically enhanced imaging properties. When in close proximity, AuNPs plasmonic fields couple together, increasing their scattering cross-section due to the formation of hot spots, improving their imaging utility. In the present study, we modified the AuNPs surface with different peptides to target the nucleus and/or the cell as a whole, resulting in similar cellular uptake but different scattering intensities. Nuclear-targeted AuNPs showed the greatest scattering due to the formation of denser nanoparticle clusters (i.e., increased localization). We also obtained a dynamic profile of AuNP localization in living cells, indicating that nuclear localization is directly related to the number of nuclear-targeting peptides on the AuNP surface. Increased localization led to increased plasmonic field coupling, resulting in significantly higher scattering intensity. Thus, biochemical targeting of plasmonic nanoparticles to subcellular components is expected to lead to more resolved imaging of cellular processes. PMID- 25126389 TI - Pancreatic steatosis: Is it related to either obesity or diabetes mellitus? AB - The accumulation of fat in the pancreatic gland has been referred to using various synonyms, such as pancreatic lipomatosis, fatty replacement, fatty infiltration, fatty pancreas, lipomatous pseudohypertrophy, non-alcoholic fatty pancreatic disease and pancreatic steatosis We believe that pancreatic steatosis is the best description of fat accumulation in the pancreatic gland without fat replacement, and this term also describes the possibility that the fat accumulation is a reversible process. A review of the existing literature was carried out, and it was found that there was notable evidence from both the pathological and the imaging point of view that pancreatic steatosis is an increasing problem due to the increasing incidence of obesity. The conclusion was that pancreatic steatosis was easily detectable using modern imaging techniques, such as ultrasonography, endoscopic ultrasonography, computed tomography and magnetic resonance imaging. Pancreatic steatosis was not due to the presence of diabetes mellitus but was highly associated with the metabolic syndrome. The possible presence of steatopancreatitis should be better evaluated, especially regarding the inflammatory cascade, and additional studies are needed which are capable of assessing whether non-alcoholic steatopancreatitis really exists as does non-alcoholic steatohepatitis. Finally, the presence of exocrine pancreatic function should be extensively evaluated in patients with pancreatic steatosis. PMID- 25126390 TI - Benefits of healthy adipose tissue in the treatment of diabetes. AB - The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin. Insulin deficiency is either absolute due to destruction or failure of pancreatic beta cells, or relative due to decreased sensitivity of peripheral tissues to insulin. The primary lesion being related to insulin, treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin. These therapies have their own limitations and complications, some of which can be life-threatening. For example, exogenous insulin administration can lead to fatal hypoglycemic episodes; islet/pancreas transplantation requires life-long immunosuppressive therapy; and anti-diabetic drugs have dangerous side effects including edema, heart failure and lactic acidosis. Thus the need remains for better safer long term treatments for diabetes. The ultimate goal in treating diabetes is to re establish glucose homeostasis, preferably through endogenously generated hormones. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism. While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro inflammatory cytokines, healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties, which can complement and/or compensate for the function of insulin. Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes, and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin. Although specific adipokines may correct diabetes, administration of individual adipokines still carries risks similar to those of insulin monotherapy. Thus a better approach is to achieve glucose homeostasis with endogenously-generated adipokines through transplantation or regeneration of healthy adipose tissue. Our recent studies on mouse models show that type 1 diabetes can be reversed without insulin through subcutaneous transplantation of embryonic brown adipose tissue, which leads to replenishment of recipients' white adipose tissue; increase of a number of beneficial adipokines; and fast and long-lasting euglycemia. Insulin independent glucose homeostasis is established through a combination of endogenously generated hormones arising from the transplant and/or newly replenished white adipose tissue. Transplantation of healthy white adipose tissue is reported to alleviate type 2 diabetes in rodent models on several occasions, and increasing the content of endogenous brown adipose tissue is known to combat obesity and type 2 diabetes in both humans and animal models. While the underlying mechanisms are not fully documented, the beneficial effects of healthy adipose tissue in improving metabolism are increasingly reported, and are worthy of attention as a powerful tool in combating metabolic disease. PMID- 25126391 TI - Inflammation in diabetic kidney disease. AB - Diabetes mellitus entails significant health problems worldwide. The pathogenesis of diabetes is multifactorial, resulting from interactions of both genetic and environmental factors that trigger a complex network of pathophysiological events, with metabolic and hemodynamic alterations. In this context, inflammation has emerged as a key pathophysiology mechanism. New pathogenic pathways will provide targets for prevention or future treatments. This review will focus on the implications of inflammation in diabetes mellitus, with special attention to inflammatory cytokines. PMID- 25126393 TI - Structured SMBG in early management of T2DM: Contributions from the St Carlos study. AB - Diabetes mellitus type 2 (T2DM) is a global pandemic that will affect 300 million people in the next decade. It has been shown that early and aggressive treatment of T2DM from the onset decreases complications, and the patient's active role is necessary to achieve better glycemic control. In order to achieve glycemic control targets, an active attitude in patients is needed, and self-monitoring of blood glucose (SMBG) plays a significant role. Nowadays, SMBG has become an important component of modern therapy for diabetes mellitus, and is even more useful if it is performed in a structured way. SMBG aids physicians and patients to achieve a specific level of glycemic control and to prevent hypoglycemia. In addition, SMBG empowers patients to achieve nutritional and physical activity goals, and helps physicians to optimize the different hypoglycemic therapies as demonstrated in the St Carlos study. This article describes the different ways of using this educational and therapeutic tool from the medical point of view as well as from the patient's perspective. PMID- 25126394 TI - Effects of exercise training on mitochondrial function in patients with type 2 diabetes. AB - Type 2 diabetes is characterized by a decreased ability of insulin to facilitate glucose uptake into insulin sensitive tissue, i.e., skeletal muscle. The mechanism behind this is at the moment unresolved. It has been suggested that increased amount of lipids inside the skeletal muscle (intramuscular triglyceride, diacylglycerol and ceramides) will impair insulin action in skeletal muscle, but data are not consistent in the human literature. It has also been hypothesized that the impaired insulin sensitivity is due to a dysfunction in the mitochondria resulting in an impaired ability to oxidize lipids, but the majority of the literature is not supporting this hypothesis. Recently it has been suggested that the production of reactive oxygen species play an essential role in skeletal muscle insulin sensitivity. It is well accepted that physical activity (endurance, strength and high intensity training) improves insulin sensitivity in healthy humans and in patients with type 2 diabetes. Whether patients with type 2 diabetes have the same beneficial effects (same improvement) as control subjects, when it comes to regular physical activity in regard to mitochondrial function, is not established in the literature. This review will focus only on the effect of physical activity on skeletal muscle (mitochondrial function) in patients with type 2 diabetes. PMID- 25126396 TI - Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus. AB - Ever since its first appearance among the multiple forms of diabetes, latent autoimmune diabetes in adults (LADA), has been the focus of endless discussions concerning mainly its existence as a special type of diabetes. In this mini review, through browsing important peer-reviewed publications, (original articles and reviews), we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity. A unique combination of immunological, clinical and metabolic characteristics has been identified in this group of patients, namely persistent islet cell antibodies, high frequency of thyroid and gastric autoimmunity, DR3 and DR4 human leukocyte antigen haplotypes, progressive loss of beta cells, adult disease onset, normal weight, defective glycaemic control, and without tendency to ketoacidosis. Although anthropomorphic measurements are useful as a first line screening, the detection of C-peptide levels and the presence of glutamic acid decarboxylase (GAD) autoantibodies is undoubtedly the sine qua non condition for a confirmatory LADA diagnosis. In point of fact, GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied. Nevertheless, the lack of diagnostic criteria and guidelines still puzzle the physicians, who struggle between early diagnosis and correct timing for insulin treatment. PMID- 25126395 TI - Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus. AB - Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM. PMID- 25126392 TI - Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? AB - Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin. Compared with individuals without diabetes, patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality, and are disproportionately affected by cardiovascular disease. Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension, dyslipidaemia and obesity in these patients. However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors. Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus. Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events. Many of these risk factors could be common history for both diabetes mellitus and cardiovascular disease, reinforcing the postulate that both disorders come independently from "common soil". The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients. PMID- 25126398 TI - Domino effect of hypomagnesemia on the innate immunity of Crohn's disease patients. AB - Digestive diseases play major role in development and complications of other disorders including diabetes. For example, Crohn's disease (CD) is an inflammatory bowel disease associated with Mycobacterium avium subspecies paratuberculosis. The inflammation is a complex process that involves the activity of both innate and adaptive immune responses. CD lesions are primarily due to T cell response, however; innate immune response has a significant role in initiating its pathogenesis. Toll-like receptors and NOD-like receptors promote the activity of nuclear factor (NF)-kappaB pathway for cytokines production. This results in the production of high levels of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6. Moreover, intestinal inflammation of CD is related to increased activity of NMDA receptors and the release of substance P. Imbalanced magnesium homeostasis in CD is a frequent finding in CD, Diabetes and others. The loss of such a major mineral affects many physiological processes in the body including its role as an immunomodulator. This review aims to (1) describe the significance of hypomagnesemia in the release of pro-inflammatory mediators in CD; (2) demonstrate effects of magnesium on pathways like NF-kappaB; (3) address the role of hypomagnesemia in the activity of CD; and (4) examine possible future research to establish a standard magnesium supplementation strategy; helping patients with CD or other disorders to maintain a sustained remission. PMID- 25126399 TI - Novel treatment approaches in hypertensive type 2 diabetic patients. AB - Type 2 diabetes mellitus (T2DM) and hypertension represent two common conditions worldwide. Their frequent association with cardiovascular diseases makes management of hypertensive patients with T2DM an important clinical priority. Carvedilol and renal denervation are two promising choices to reduce plasma glucose levels and blood pressure in hypertensive patients with T2DM to reduce future complications and improve clinical outcomes and prognosis. Pathophysiological mechanisms of both options are under investigation, but one of the most accepted is an attenuation in sympathetic nervous system activity which lowers blood pressure and improves insulin sensitivity. Choice of these therapeutic approaches should be individualized based on specific characteristics of each patient. Further investigations are needed to determine when to consider their use in clinical practice. PMID- 25126397 TI - SH2B1 regulation of energy balance, body weight, and glucose metabolism. AB - The Src homology 2B (SH2B) family members (SH2B1, SH2B2 and SH2B3) are adaptor signaling proteins containing characteristic SH2 and PH domains. SH2B1 (also called SH2-B and PSM) and SH2B2 (also called APS) are able to form homo- or hetero-dimers via their N-terminal dimerization domains. Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins, including Janus kinase 2 (JAK2), TrkA, insulin receptors, insulin-like growth factor-1 receptors, insulin receptor substrate-1 (IRS1), and IRS2. SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/IRS1/2 signaling complex. SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins. Accordingly, genetic deletion of SH2B1 results in severe leptin resistance, insulin resistance, hyperphagia, obesity, and type 2 diabetes in mice. Neuron-specific overexpression of SH2B1beta transgenes protects against diet-induced obesity and insulin resistance. SH2B1 in pancreatic beta cells promotes beta cell expansion and insulin secretion to counteract insulin resistance in obesity. Moreover, numerous SH2B1 mutations are genetically linked to leptin resistance, insulin resistance, obesity, and type 2 diabetes in humans. Unlike SH2B1, SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis. The metabolic function of the SH2B family is conserved from insects to humans. PMID- 25126400 TI - Choice of wound care in diabetic foot ulcer: A practical approach. AB - Diabetic foot ulcers are the consequence of multiple factors including peripheral neuropathy, decreased blood supply, high plantar pressures, etc., and pose a significant risk for morbidity, limb loss and mortality. The critical aspects of the wound healing mechanism and host physiological status in patients with diabetes necessitate the selection of an appropriate treatment strategy based on the complexity and type of wound. In addition to systemic antibiotics and surgical intervention, wound care is considered to be an important component of diabetic foot ulcer management. This article will focus on the use of different wound care materials in diabetic foot. From a clinical perspective, it is important to decide on the wound care material depending on the type and grade of the ulcer. This article will also provide clinicians with a simple approach to the choice of wound care materials in diabetic foot ulcer. PMID- 25126401 TI - Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia. AB - AIM: To investigate the role of protein tyrosin phosphatase 22 (PTPN22), maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes (T1D) in Continental Italy and Sardinian populations. METHODS: Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032 healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia. PTPN22 genotype was determined by DNA analysis. Maternal age at conception and age at onset of disease were obtained from clinical records. chi(2) test of independence, student t test for differences between means and odds ratio analysis were carried out by SPSS programs. Three way contingency table analysis was carried out according to Sokal and Rohlf. RESULTS: The pattern of association between PTPN22 and T1D is similar in Continental Italy and Sardinia: the proportion of *T allele carriers is 13.6% in T1D vs 6.7% in controls in Continental Italy while in Sardinia is 7.3% in T1D vs 4.4% in controls. The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy: the proportion of newborn from mother aging more than 32 years is 89.3% in T1D vs 32.7% in consecutive newborn in Sardinia (P < 10(-6)) while in Continental Italy is 32.2% in T1D vs 19.1% in consecutive newborns (P = 0.005). This points to an important role of ethnicity. A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia. PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia. Maternal age does not influence significantly age at onset in Italy (8.2 years in T1D infants from mothers aging 32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years: P = 0.824) while in Sardinia a border line effect is observed (5.75 years in T1D infants from mothers aging 32 years or less vs 7.54 years in T1D infants from mothers aging more than 32 years: P = 0.062). No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males (8.07 years in males vs 6.3 years in females: P = 0.002). CONCLUSION: The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D. PMID- 25126402 TI - Conventional insulin vs insulin infusion therapy in acute coronary syndrome diabetic patients. AB - AIM: To evaluate the impact on glucose variability (GLUCV) of an nurse implemented insulin infusion protocol when compared with a conventional insulin treatment during the day-to-day clinical activity. METHODS: We enrolled 44 type 2 diabetic patients (n = 32 males; n = 12 females) with acute coronary syndrome (ACS) and randomy assigned to standard a subcutaneous insulin treatment (n = 23) or a nurse-implemented continuous intravenous insulin infusion protocol (n = 21). We utilized some parameters of GLUCV representing well-known surrogate markers of prognosis, i.e., glucose standard deviation (SD), the mean daily delta glucose (mean of daily difference between maximum and minimum glucose), and the coefficient of variation (CV) of glucose, expressed as percent glucose (SD)/glucose (mean). RESULTS: At the admission, first fasting blood glucose, pharmacological treatments (insulin and/or anti-diabetic drugs) prior to entering the study and basal glycated hemoglobin (HbA1c) were observed in the two groups treated with subcutaneous or intravenous insulin infusion, respectively. When compared with patients submitted to standard therapy, insulin-infused patients showed both increased first 24-h (median 6.9 mmol/L vs 5.7 mmol/L P < 0.045) and overall hospitalization delta glucose (median 10.9 mmol/L vs 9.3 mmol/L, P < 0.028), with a tendency to a significant increase in first 24-h glycaemic CV (23.1% vs 19.6%, P < 0.053). Severe hypoglycaemia was rare (14.3%), and it was observed only in 3 patients receiving insulin infusion therapy. HbA1c values measured during hospitalization and 3 mo after discharge did not differ in the two groups of treatment. CONCLUSION: Our pilot data suggest that no real benefit in terms of GLUCV is observed when routinely managing blood glucose by insulin infusion therapy in type 2 diabetic ACS hospitalized patients in respect to conventional insulin treatment. PMID- 25126403 TI - Fifteen-year follow-up of quality of life in type 1 diabetes mellitus. AB - AIM: To evaluate metabolic control and health-related quality of life (HRQOL) in a type 1 diabetes mellitus (T1DM) population. METHODS: As part of a prospective cohort study, 283 T1DM patients treated with various insulin treatment modalities including multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII) were examined annually. HRQOL was measured using the SF-36 and EuroQol questionnaires. Data regarding HRQOL, glycaemic and metabolic control from baseline and follow-up measures in 2002 and 2010 were analysed. Linear mixed models were used to calculate estimated values and differences between the three moments in time and the three treatment modalities. RESULTS: Significant changes [mean Delta (95%CI)] in body mass index [2.4 kg/m(2) (1.0, 3.8)], systolic blood pressure [-6.4 mmHg (-11.4, -1.3)] and EuroQol-VAS [-7.3 (-11.4, -3.3)] were observed over time. In 2010, 168 patients were lost to follow-up. Regarding mode of therapy, 52 patients remained on MDI, 28 remained on CSII, and 33 patients switched from MDI to CSII during follow-up. Among patients on MDI, HRQOL decreased significantly over time: mental component summary [-9.8 (-16.3, -3.2)], physical component summary [-8.6 (-15.3, -1.8)] and EuroQol-VAS [-8.1 (-14.0, 2.3)], P < 0.05 for all. For patients using CSII, the EuroQol-VAS decreased [-9.6 (-17.5, -1.7)]. None of the changes over time in HRQOL differed significantly with the changes over time within the other treatment groups. CONCLUSION: No differences with respect to metabolic and HRQOL parameters between the various insulin treatment modalities were observed after 15 years of follow-up in T1DM patients. PMID- 25126404 TI - The Early Determinants of Adult Health Study. AB - This issue of the Journal features collaborative follow-up studies of two unique pregnancy cohorts recruited during 1959-1966 in the United States. Here we introduce the Early Determinants of Adult Health (EDAH) study. EDAH was designed to compare health outcomes in midlife (age 40s) for same-sex siblings discordant on birthweight for gestational age. A sufficient sample of discordant siblings could only be obtained by combining these two cohorts in a single follow-up study. All of the subsequent six papers are either based upon the EDAH sample or are related to it in various ways. For example, three papers report results from studies that significantly extended the 'core' EDAH sample to address specific questions. We first present the overall design of and rationale for the EDAH study. Then we offer a synopsis of past work with the two cohorts to provide a context for both EDAH and the related studies. Next, we describe the recruitment and assessment procedures for the core EDAH sample. This includes the process of sampling and recruitment of potential participants; a comparison of those who were assessed and not assessed based on archived data; the methods used in the adult follow-up assessment; and the characteristics at follow-up of those who were assessed. We provide online supplementary tables with much further detail. Finally, we note further work in progress on EDAH and related studies, and draw attention to the broader implications of this endeavor. PMID- 25126405 TI - Serum microRNA profiles in children with autism. AB - BACKGROUND: As regulators of gene expression, microRNAs (miRNAs) play a key role in the transcriptional networks of the developing human brain. Circulating miRNAs in the serum and plasma are remarkably stable and are suggested to have promise as noninvasive biomarkers for neurological and neurodevelopmental disorders. We examined the serum expression profiles of neurologically relevant miRNAs in autism spectrum disorder (ASD), a complex neurodevelopmental disorder characterized by multiple deficits in communication, social interaction and behavior. METHODS: Total RNA, including miRNA, was extracted from the serum samples of 55 individuals with ASD and 55 age- and sex-matched control subjects, and the mature miRNAs were selectively converted into cDNA. Initially, the expression of 125 mature miRNAs was compared between pooled control and ASD samples. The differential expression of 14 miRNAs was further validated by SYBR Green quantitative PCR of individual samples. Receiver-operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of miRNAs. The target genes and pathways of miRNAs were predicted using DIANA mirPath software. RESULTS: Thirteen miRNAs were differentially expressed in ASD individuals compared to the controls. MiR-151a-3p, miR-181b-5p, miR-320a, miR 328, miR-433, miR-489, miR-572, and miR-663a were downregulated, while miR-101 3p, miR-106b-5p, miR-130a-3p, miR-195-5p, and miR-19b-3p were upregulated. Five miRNAs showed good predictive power for distinguishing individuals with ASD. The target genes of these miRNAs were enriched in several crucial neurological pathways. CONCLUSIONS: This is the first study of serum miRNAs in ASD individuals. The results suggest that a set of serum miRNAs might serve as a possible noninvasive biomarker for ASD. PMID- 25126406 TI - Proteomic analysis of post mortem brain tissue from autism patients: evidence for opposite changes in prefrontal cortex and cerebellum in synaptic connectivity related proteins. AB - BACKGROUND: Autism is a neurodevelopmental disorder characterized by impaired language, communication and social skills. Although genetic studies have been carried out in this field, none of the genes identified have led to an explanation of the underlying causes. Here, we have investigated molecular alterations by proteomic profiling of post mortem brain samples from autism patients and controls. The analysis focussed on prefrontal cortex and cerebellum as previous studies have found that these two brain regions are structurally and functionally connected, and they have been implicated in autism. METHODS: Post mortem prefrontal cortex and cerebellum samples from autism patients and matched controls were analysed using selected reaction monitoring mass spectrometry (SRM MS). The main objective was to identify significantly altered proteins and biological pathways and to compare these across these two brain regions. RESULTS: Targeted SRM-MS resulted in identification of altered levels of proteins related to myelination, synaptic vesicle regulation and energy metabolism. This showed decreased levels of the immature astrocyte marker vimentin in both brain regions, suggesting a decrease in astrocyte precursor cells. Also, decreased levels of proteins associated with myelination and increased synaptic and energy-related proteins were found in the prefrontal cortex, indicative of increased synaptic connectivity. Finally, opposite directional changes were found for myelination and synaptic proteins in the cerebellum. CONCLUSION: These findings suggest altered structural and/or functional connectivity in the prefrontal cortex and cerebellum in autism patients, as shown by opposite effects on proteins involved in myelination and synaptic function. Further investigation of these findings could help to increase our understanding of the mechanisms underlying autism relating to brain connectivity, with the ultimate aim of facilitating novel therapeutic approaches. PMID- 25126407 TI - Level of A1C control and its predictors among Lebanese type 2 diabetic patients. AB - AIM: Lebanon is among the top 10 countries with the highest prevalence of diabetes in the Middle East region with estimates reaching as high as 16.6% in adults aged 20-79 years. The objective of this study was to assess the level of A1C control among a cohort of type 2 diabetic patients and factors associated with uncontrolled A1C. METHODS: We carried out a retrospective observational study among type 2 diabetes mellitus patients attending an outpatient endocrinologist's clinic between June 2008 and July 2012 in Beirut, Lebanon. Two groups were compared, based on their diabetic control (A1C < 7% and A1C >= 7%). RESULTS: A total of 551 patients were included in this study, where 31.8% attained A1C control. Crude analyses showed that some factors were significantly associated with uncontrolled A1C, and these were long-standing diabetes, diabetes related complications, uncontrolled blood pressure, lipid profile, as well as the use of metformin, sulfonylurea, or insulin. When multivariate analysis was carried out, the chances of having uncontrolled A1C were significantly higher among patients who developed neuropathy (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.11-3.90), had uncontrolled triglycerides (OR 1.98, 95% CI 1.33 2.94), used insulin (OR 4.52, 95% CI 2.32-8.83), and sulfonylureas (OR 2.88, 95% CI 1.88-4.40). CONCLUSION: Uncontrolled diabetes is more likely to exist in patients with neuropathy, uncontrolled triglycerides and those using insulin or sulfonylurea. Further research is needed to confirm the findings. PMID- 25126408 TI - Renal effects of dapagliflozin in patients with type 2 diabetes. AB - Diabetes mellitus was originally conceived as a renal disorder. In the last decade, however, there has been renewed interest in role of the kidney in the development and maintenance of high glucose levels. This has led to the development of novel agents to inhibit sodium glucose transporter-2 (SGLT2) as a means to better control glucose levels and at the same time augment calorie wasting and lower insulin, blood pressure and uric acid levels. Such actions, indirectly, may also have benefits for the prevention of diabetic complications including renal disease. However, there are also data to support the potential for direct renoprotective actions arising from inhibition of SGLT2, including actions to attenuate diabetes-associated hyperfiltration and tubular hypertrophy, as well as reduce the tubular toxicity of glucose. Some studies have demonstrated significant reductions in albumin excretion in various experimental models, independent of its effects on blood pressure or glucose control. Although promising, such actions remain to be established by comprehensive clinical trials with a renal focus, many of which are currently in progress. This article reviews the clinical and experimental data pertaining to the renal effects of SGLT2 inhibition with a particular focus on dapaglifozin. PMID- 25126409 TI - Comprehensive analysis of published studies involving systemic treatment for chondrosarcoma of bone between 2000 and 2013. AB - BACKGROUND: The majority of patients with chondrosarcoma of bone have an excellent overall survival after local therapy. However, in case of unresectable locally advanced or metastatic disease the outcome is poor and limited treatment options exist. Therefore we conducted a survey of clinical phase I or II trials and retrospective studies that described systemic therapy for chondrosarcoma patients. MATERIALS AND METHODS: Using PubMed, clinicaltrials.gov, the Cochrane controlled trial register and American Society of Clinical Oncology (ASCO) abstracts a literature survey was conducted. From the identified items, data were collected by a systematic analysis. We limited our search to semi-recent studies published between 2000 and 2013 to include modern drugs, imaging techniques and disease evaluations. RESULTS: A total of 31 studies were found which met the criteria: 9 phase I trials, 11 phase II and 8 retrospective studies. In these studies 855 chondrosarcoma patients were reported. The tested drugs were mostly non-cytotoxic, either alone or in combination with another non-cytotoxic agent or chemotherapy. Currently two phase I trials, one phase IB/II trial and three phase II trials are enrolling chondrosarcoma patients. CONCLUSION: Because chondrosarcoma of bone is an orphan disease it is difficult to conduct clinical trials. The meagre outcome data for locally advanced or metastatic patients indicate that new treatment options are needed. For the phase I trials it is difficult to draw conclusions because of the low numbers of chondrosarcoma patients enrolled, and at different dose levels. Some phase II trials show promising results which support further research. Retrospective studies are encouraged as they could add to the limited data available. Efforts to increase the number of studies for this orphan disease are urgently needed. PMID- 25110576 TI - Functional characterization of Candida albicans Hos2 histone deacetylase. AB - Candida albicans is a mucosal commensal organism capable of causing superficial (oral and vaginal thrush) infections in immune normal hosts, but is a major pathogen causing systemic and mucosal infections in immunocompromised individuals. Azoles have been very effective anti-fungal agents and the mainstay in treating opportunistic mold and yeast infections. Azole resistant strains have emerged compromising the utility of this class of drugs. It has been shown that azole resistance can be reversed by the co-administration of a histone deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report here the cloning and functional characterization of HOS2 (High Osmolarity Sensitive) , a gene coding for fungal histone deacetylase from C. albicans. Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not inhibited by class I inhibitors such as MS-275. This in vitro enzymatic assay, which is amenable to high throughput could be used for screening potent fungal Hos2 inhibitors that could be a potential anti-fungal adjuvant. Purified Hos2 protein consistently deacetylated tubulins, rather than histones from TSA-treated cells. Hos2 has been reported to be a putative NAD+ dependent histone deacetylase, a feature of sirtuins. We assayed for sirtuin activation with resveratrol and purified Hos2 protein and did not find any sirtuin activity. PMID- 25126410 TI - Ring finger protein 39 genetic variants associate with HIV-1 plasma viral loads and its replication in cell culture. AB - BACKGROUND: The human immunodeficiency virus (HIV-1) exploits host proteins to complete its life cycle. Genome-wide siRNA approaches suggested that host proteins affect HIV-1 replication. However, the results barely overlapped. RING finger protein 39 (RNF39) has been identified from genome-wide association studies. However, its function during HIV-1 replication remains unclear. METHODS AND RESULTS: We investigated the relationship between common RNF39 genetic variants and HIV-1 viral loads. The effect of RNF39 protein knockdown or overexpression on HIV-1 replication was then investigated in different cell lines. Two genetic variants were associated with HIV-1 viral loads. Patients with the ht1-GG/GG haplotype presented lower RNF39 expression levels and lower HIV-1 viral load. RNF39 knockdown inhibited HIV-1 expression. CONCLUSIONS: RNF39 protein may be involved in HIV-1 replication as observed in genetic studies on patients with HIV-1 and in in vitro cell cultures. PMID- 25110577 TI - Accumulation of oocytes and/or embryos by vitrification: a new strategy for managing poor responder patients undergoing pre implantation diagnosis. AB - BACKGROUND: Low (or poor) responder patients are women who require large doses of stimulation medications and produce less than an optimal number of oocytes during IVF cycles. Low responder patients produce few oocytes and embryos, which significantly reduces their chances for success in a preimplantation genetic diagnosis (PGD) cycle. Accumulation of vitrified oocytes or embryos before the actual PGD cycle is a possible strategy that might increase patient's chances for a healthy pregnancy. AIM OF THE STUDY: This retrospective study evaluates the efficacy of a PGD program in low responder patients after repeated ovarian stimulation cycles with cumulative vitrification of oocytes and embryos. METHODS: Over a period of 30 months, 13 patients entering the PGD program were identified as poor responders after their first ovarian stimulation. These patients started a PGD cycle for one of the following indications: history of recurrent implantation failure (n=1), cystic fibrosis (n=1), X-linked microtubular myopathy (n=1), recurrent miscarriages (n=5), Duchene muscular dystrophy (n=1), chromosomal translocation (n=1) and high sperm aneuploidy (n=1). After multiple ovarian hormonal stimulations patients had either all mature oocytes (Group A; 3 patients) or all of their day 2 embryos vitrified (group B; 10 patients). Mean total number of oocyte collections per patient was 2.3 (range: 2 - 5 cycles). RESULTS: In the actual PGD cycle, all vitrified oocytes from group A patients were warmed and underwent intra cytoplasmic sperm injection (ICSI) followed by culture up to day 3. For group B patients all vitrified day 2 embryos were warmed and cultured overnight. On day 3 of culture, all embryos from Group A and B had blastomere biopsy followed by genetic analysis. In group A, 20 embryos were found suitable for biopsy and genetic analysis; at least one healthy embryo was available for transfer for each patient. For group B, 72 embryos in total were available for biopsy and PGD. All patients, except one, had at least one healthy day 5 embryo for transfer (mean number of 2.1 embryos per transfer). Nine patients had a clinical pregnancy; 7 patients delivered a healthy baby. CONCLUSION: Low responder patients entering a PGD program might increase their chances for a healthy pregnancy by repeat ovarian stimulation in combination with cumulative oocyte or embryo vitrification. PMID- 25110576 TI - Functional characterization of Candida albicans Hos2 histone deacetylase. AB - Candida albicans is a mucosal commensal organism capable of causing superficial (oral and vaginal thrush) infections in immune normal hosts, but is a major pathogen causing systemic and mucosal infections in immunocompromised individuals. Azoles have been very effective anti-fungal agents and the mainstay in treating opportunistic mold and yeast infections. Azole resistant strains have emerged compromising the utility of this class of drugs. It has been shown that azole resistance can be reversed by the co-administration of a histone deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report here the cloning and functional characterization of HOS2 (High Osmolarity Sensitive) , a gene coding for fungal histone deacetylase from C. albicans. Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not inhibited by class I inhibitors such as MS-275. This in vitro enzymatic assay, which is amenable to high throughput could be used for screening potent fungal Hos2 inhibitors that could be a potential anti-fungal adjuvant. Purified Hos2 protein consistently deacetylated tubulins, rather than histones from TSA-treated cells. Hos2 has been reported to be a putative NAD+ dependent histone deacetylase, a feature of sirtuins. We assayed for sirtuin activation with resveratrol and purified Hos2 protein and did not find any sirtuin activity. PMID- 25126416 TI - Characterization of a multilayer heparin coating for biomolecule presentation to human mesenchymal stem cell spheroids. AB - Mesenchymal stem cells therapies have the potential to treat many pathologies, however, controlling cell fate after implantation remains challenging. We have used a multilayer technology to graft a range of 5 MUg/mL - 5 mg/mL heparin onto the surface of MSC aggregates. Heparin coating does not affect cell viability (seen through LIVE/DEAD staining), cell anti-inflammatory properties (seen through co-culture with activated monocytes)and facilitates sequestration by coated cells of a growth factor (TGF-beta1) that remains bioactive. This system can maximize therapeutic potential of MSC-based treatments because the cell surface-loaded protein could both signal to the cells to influence transplanted cell fate and be released into the surrounding environment to help repair injured tissue. PMID- 25126414 TI - Cytoplasmic nanojunctions between lysosomes and sarcoplasmic reticulum are required for specific calcium signaling. AB - Herein we demonstrate how nanojunctions between lysosomes and sarcoplasmic reticulum (L-SR junctions) serve to couple lysosomal activation to regenerative, ryanodine receptor-mediated cellular Ca (2+) waves. In pulmonary artery smooth muscle cells (PASMCs) it has been proposed that nicotinic acid adenine dinucleotide phosphate (NAADP) triggers increases in cytoplasmic Ca (2+) via L-SR junctions, in a manner that requires initial Ca (2+) release from lysosomes and subsequent Ca (2+)-induced Ca (2+) release (CICR) via ryanodine receptor (RyR) subtype 3 on the SR membrane proximal to lysosomes. L-SR junction membrane separation has been estimated to be < 400 nm and thus beyond the resolution of light microscopy, which has restricted detailed investigations of the junctional coupling process. The present study utilizes standard and tomographic transmission electron microscopy to provide a thorough ultrastructural characterization of the L-SR junctions in PASMCs. We show that L-SR nanojunctions are prominent features within these cells and estimate that the junctional membrane separation and extension are about 15 nm and 300 nm, respectively. Furthermore, we develop a quantitative model of the L-SR junction using these measurements, prior kinetic and specific Ca (2+) signal information as input data. Simulations of NAADP-dependent junctional Ca (2+) transients demonstrate that the magnitude of these signals can breach the threshold for CICR via RyR3. By correlation analysis of live cell Ca (2+) signals and simulated Ca (2+) transients within L-SR junctions, we estimate that "trigger zones" comprising 60 100 junctions are required to confer a signal of similar magnitude. This is compatible with the 110 lysosomes/cell estimated from our ultrastructural observations. Most importantly, our model shows that increasing the L-SR junctional width above 50 nm lowers the magnitude of junctional [Ca (2+)] such that there is a failure to breach the threshold for CICR via RyR3. L-SR junctions are therefore a pre-requisite for efficient Ca (2+)signal coupling and may contribute to cellular function in health and disease. PMID- 25126415 TI - Incidence and predictors of surgical site infections following caesarean sections at Bugando Medical Centre, Mwanza, Tanzania. AB - BACKGROUND: Surgical site infection (SSI) is the second most common infectious complication after urinary tract infection following a delivery by caesarean section (CS). At Bugando Medical Centre there has no study documenting the epidemiology of SSI after CS despite the large number of CSs performed and the relatively common occurrence of SSIs. METHODS: This was a prospective cohort study involving pregnant women who underwent a CS between October 2011 and February 2012 at Bugando Medical Centre. A total of 345 pregnant women were enrolled. Preoperative, intraoperative and postoperative data were collected using a standardized questionnaire. Wound specimens were collected and processed as per standard operative procedures; and susceptibility testing was carried out using a disc diffusion technique. Data was analyzed using STATA version 11. RESULTS: The overall cumulative incidence of SSI was 10.9% with an incidence rate of 37.5 per 10,000 people/day (95% CI, 26.8-52.4). The median time from CS to the development of SSI was 7 days (interquartile range [IQR] = 6-9 days). Six independent risk factors for post caesarean SSI as identified in this study by multivariate analysis are: hypertensive disorders of pregnancy (HR: 2.5; 95% CI, 1.1-5.6; P = 0.021), severe anaemia (HR: 3.8; 95% CI, 1.2-12.4, P = 0.028), surgical wound class III (HR: 2.4; 95% CI, 1.1-5.0; P = 0.021), multiple vaginal examinations (HR: 2.5; 95% CI, 1.2-5.1; P = 0.011), prolonged duration of operation (HR: 2.6; 95% CI, 1.2-5.5; P = 0.015) and an operation performed by an intern or junior doctor (HR: 4.0; 95% CI, 1.7-9.2; P = 0.001). Staphylococcus aureus was the most common organism (27.3%), followed by Klebsiella pneumoniae (22.7%). Patients with a SSI had a longer average hospital stay than those without a SSI (12.7 +/- 6.9 vs. 4 +/- 1.7; P < 0.0001) and the case fatality rate among patients with a SSI was 2.9%. CONCLUSION: SSIs are common among women undergoing CSs at Bugando Medical Centre. SSIs were commonly associated with multiple factors. Strategies to control these factors are urgently needed to control SSIs post CS at Bugando Medical Centre and other centres in developing countries. PMID- 25126417 TI - Mortality attributable to tobacco: review of different methods. AB - BACKGROUND: One of the most important measures for ascertaining the impact of tobacco is the estimation of the mortality attributable to its use. Several indirect methods of quantification are available. The objective of the article is to assess methodologies published and applied in calculating mortality attributable to smoking. METHODS: A review of the literature was made for the period 1998 to 2005, in the electronic databases MEDLINE. Twelve articles were selected for analysis. RESULTS: The most widely used methods were the prevalence methods, followed by smoking impact ration method. Ezzati and Lopez showed that the general rate of Smoking attributable mortality (SAM) globally was 12% (18% in men). Across countries, attributable fractions of total adult deaths ranged from 8% in Southern Africa, 13.6% in Brazil (18.1% in men) and 25% in Hong Kong (33% in men). CONCLUSION: The variations can be attributed to methodological differences and to different estimates of the main tobacco-related illnesses and tobacco prevalence. All methods show limitations of one type or another, yet there is no consensus as to which furnishes the best information. PMID- 25126418 TI - Smoking-attributable mortality in Morocco: results of a prevalence-based study in Casablanca. AB - BACKGROUND: Tobacco control measurements' had little impact on smoking prevalence in Morocco. The aim of this study is to provide first data on smoking attributable mortality in Morocco. METHOD: The Smoking-Attributable Mortality, Morbidity and Economic Costs (SAMMEC) software was used to estimate the smoking attributable mortality (SAM) in Casablanca region in 2012. Smoking prevalence and mortality data of people aged 35 years or older were obtained from the national survey on tobacco "Marta" and from Health Ministry Mortality System, respectively. RESULTS: Of the 5261deaths of persons aged 35 years and older, 508 (9.7%) were attributable to cigarette smoking. This total represents 16.2% of all male deaths (n =448) and 2.0% (n =80) of all female deaths in this region. The leading four causes of smoking attributable deaths were lung cancer (177), chronic airways obstruction (76), ischemic heart disease (39), and cerebrovascular disease (31). CONCLUSION: Tobacco use caused one out of six deaths in Casablanca in 2012. Four leading causes (lung cancer, ischemic heart disease, cerebrovascular disease and chronic airways obstruction,) accounted for 51.6% of SAM. Effective and comprehensive actions must be taken in order to slow this epidemic in Morocco. PMID- 25126419 TI - A Centre for the Diagnosis and Treatment of Tuberculosis (CDT) in a resource limited setting: a dragnet for patients with heart disease? AB - BACKGROUND: Cardiovascular disease is a growing public health problem in sub Saharan Africa. Cough and dyspnea are symptoms of both lung diseases and heart failure. This study aimed at determining the contribution of cardiac diseases versus pulmonary diseases in the etiological profile of patients presenting with cough and dyspnea in a Center for the Diagnosis and Treatment of Tuberculosis (CDT), in a semi-rural area in Cameroon. METHODS: This is a cross-sectional analysis of data from patients aged 18 years or more who consulted for cough and or dyspnea between December 2009 and December 2010 at the CDT of Lafe-Baleng, Bafoussam, Cameroon. RESULTS: A total of 1196 patients were received for various complaints during the study period; 348 (29.1%) of them presented with cough and or dyspnea, and were included in the study. 186 patients (53.4%; 95% CI: 48.2 58.6) had a pure cardiac disease, while 122 patients (35.1%; 95% CI: 30.2-40.2) had a pulmonary disease. The prevalence of hypertension was 50.9%, and hypertensive heart disease was the most frequent cardiac disease with a prevalence rate of 37.6%. Heart failure was diagnosed in 222 patients, representing 63.8% (95% CI: 58.9-68.9) of patients with cough and or dyspnea, and 18.6% (95% CI: 16.5-21.0) of all the patients received at the CDT of Lafe-Baleng during the study period. Compared to patients with a pulmonary disease, patients with cardiac disease were older (p < 0.001) and more likely to present with dyspnea (p < 0.001) and to have hypertension (p < 0.001). CONCLUSION: We found a high prevalence of heart failure in this Centre for the Diagnosis and Treatment of Tuberculosis thus, a veritable dragnet for patients with heart disease. Our findings emphasize the urgent need to increase the access to cardiovascular care and to continuously raise the awareness of the communities on cardiovascular diseases in Cameroon. PMID- 25126420 TI - Impact of community-based interventions on HIV knowledge, attitudes, and transmission. AB - In 2012, an estimated 35.3 million people lived with HIV, while approximately two million new HIV infections were reported. Community-based interventions (CBIs) for the prevention and control of HIV allow increased access and ease availability of medical care to population at risk, or already infected with, HIV. This paper evaluates the impact of CBIs on HIV knowledge, attitudes, and transmission. We included 39 studies on educational activities, counseling sessions, home visits, mentoring, women's groups, peer leadership, and street outreach activities in community settings that aimed to increase awareness on HIV/AIDS risk factors and ensure treatment adherence. Our review findings suggest that CBIs to increase HIV awareness and risk reduction are effective in improving knowledge, attitudes, and practice outcomes as evidenced by the increased knowledge scores for HIV/AIDS (SMD: 0.66, 95% CI: 0.25, 1.07), protected sexual encounters (RR: 1.19, 95% CI: 1.13, 1.25), condom use (SMD: 0.96, 95% CI: 0.03, 1.58), and decreased frequency of sexual intercourse (RR: 0.76, 95% CI: 0.61, 0.96). Analysis shows that CBIs did not have any significant impact on scores for self-efficacy and communication. We found very limited evidence on community based management for HIV infected population and prevention of mother- to-child transmission (MTCT) for HIV-infected pregnant women. Qualitative synthesis suggests that establishment of community support at the onset of HIV prevention programs leads to community acceptance and engagement. School-based delivery of HIV prevention education and contraceptive distribution have also been advocated as potential strategies to target high-risk youth group. Future studies should focus on evaluating the effectiveness of community delivery platforms for prevention of MTCT, and various emerging models of care to improve morbidity and mortality outcomes. PMID- 25126423 TI - Evaluation of the new digital goldmann applanation tonometer for measuring intraocular pressure. AB - Purpose. To compare a new digital Goldmann applanation tonometer (dGAT) that measures intraocular pressure (IOP) in 0.1 mmHg increments to a standard Goldmann applanation tonometer (sGAT). Methods. This study included 116 eyes of 60 subjects. A single examiner first measured IOP in triplicate using either sGAT or dGAT, which was randomly chosen. After a 5-minute interval, the next set of three consecutive IOP was measured using the other GAT. Results. The mean IOP measured with sGAT was 16.27 +/- 6.68 mmHg and 16.35 +/- 6.69 mmHg with dGAT. Pearson's correlation coefficient was 0.998 (P < 0.01). The subjects were divided into three groups based on the mean IOP: IOP < 14 mmHg, 14-20 mmHg, or >20 mmHg. The Pearson's correlation coefficient within each group was 0.935, 0.972, and 0.997 (P < 0.01), respectively. The difference within the three consecutive IOP measurements (maximum-minimum) for dGAT (0.72 +/- 0.34 mmHg) was significantly smaller than those with sGAT (0.92 +/- 0.42 mmHg, P < 0.01). Even in patients with equal IOP (zero left-right difference) with sGAT (n = 30), dGAT detected IOP differences between the left and right eyes (0.47 +/- 0.31 mmHg). Conclusion. Compared to sGAT, dGAT measurements are highly reproducible and less variable. PMID- 25126421 TI - A melanoma helper peptide vaccine increases Th1 cytokine production by leukocytes in peripheral blood and immunized lymph nodes. AB - BACKGROUND: Cancers produce soluble and cell-associated molecules that can suppress or alter antitumor immunity. Preclinical studies suggest the disease burden may alter the cytokine profile of helper T cell responses to cancer antigens. We studied cytokine production by helper T cells responding to vaccination with 6 melanoma helper peptides (6MHP) in blood and lymph nodes. METHODS: Twenty-three patients with stage IIIB-IV melanoma received a 6MHP vaccine. Antigen-reactive T cells from blood and draining lymph nodes were cultured, exposed to antigen, and then supernatants (days 2 and 5) were assayed for Th1 and Th2 cytokines. Results from 4 time points were compared to pre vaccine levels. RESULTS: Cytokine responses to vaccinating peptides were observed in 83% of patients. Th1 favoring responses were most common (17 of 19 responders). The most abundant cytokines produced were IFN-gamma and IL-5 in the PBMC's. IL-2 responses predominated in cells obtained from draining lymph nodes in 2-day culture but not in 5-day cultures. Patients with clinically measurable disease produced similar levels of total cytokine and similar degree of Th1 polarization as patients with no evidence of disease (NED). CONCLUSIONS: The MHC class II-associated peptides used in this study induced helper T cells with a Th1 biased cytokine response in both PBMC and sentinel immunized nodes. Most patients can mount a Th1 dominant response to these peptides. Future studies are needed to test newer vaccine adjuvants in combination with these peptides. TRIAL REGISTRATION: CDR0000378171, Clinicaltrials: NCT00089219. PMID- 25126422 TI - Psychogenic Stress in Hospitalized Dogs: Cross Species Comparisons, Implications for Health Care, and the Challenges of Evaluation. AB - Evidence to support the existence of health consequences of psychogenic stress has been documented across a range of domestic species. A general understanding of methods of recognition and means of mitigation of psychogenic stress in hospitalized animals is arguably an important feature of the continuing efforts of clinicians to improve the well-being and health of dogs and other veterinary patients. The intent of this review is to describe, in a variety of species: the physiology of the stress syndrome, with particular attention to the hypothalamic pituitary-adrenal axis; causes and characteristics of psychogenic stress; mechanisms and sequelae of stress-induced immune dysfunction; and other adverse effects of stress on health outcomes. Following that, we describe general aspects of the measurement of stress and the role of physiological measures and behavioral signals that may predict stress in hospitalized animals, specifically focusing on dogs. PMID- 25126424 TI - Pain and Anxiety versus Sense of Family Support in Lung Cancer Patients. AB - Lung cancer is a stressful condition for both patient and family. The anxiety and pain accompanying cancer and its treatment have a significant negative influence on the patient's quality of life. The aim of this study was to investigate the correlation between anxiety, pain, and perceived family support in a sample of lung cancer patients. The sample consisted of a total of 101 lung cancer outpatients receiving treatment at the oncology department of a general hospital. Anxiety, pain (severity and impact on everyday life), and perceived family support were assessed using Spielberger's State-Trait Anxiety Inventory, the Brief Pain Inventory, and the Family Support Scale, respectively. Statistical analyses revealed correlations between anxiety, pain, and family support as perceived by the patients. The intensity of pain had a positive correlation with both state and trait anxiety and a negative correlation with family support. Anxiety (state and trait) had a significant negative correlation with family support. In conclusion, high prevalence rates of anxiety disorders were observed in lung cancer patients. Females appeared more susceptible to anxiety symptoms with a less sense of family support. A negative correlation was evidenced between family support and anxiety and a positive one between anxiety and pain. PMID- 25126425 TI - Gestational trophoblastic disease: a multimodality imaging approach with impact on diagnosis and management. AB - Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative beta hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI) is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extrauterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT), and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography) and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity. PMID- 25126426 TI - Saphenous vein sparing superficial inguinal dissection in lower extremity melanoma. AB - Aim. The classic inguinal lymph node dissection is the main step for the regional control of the lower extremity melanoma, but this surgical procedure is associated with significant postoperative morbidity. The permanent lymphedema is the most devastating long-term complication leading to a significant decrease in the patient's quality of life. In this study we present our experience with modified, saphenous vein sparing, inguinal lymph node dissections for patients with melanoma of the lower extremity. Methods. Twenty one patients (10 women, 11 men) who underwent saphenous vein sparing superficial inguinal lymph node dissection for the melanoma of lower extremity were included in this study. The effects of saphenous vein sparing on postoperative complications were evaluated. Results. We have observed the decreased rate of long-term lymphedema in patients undergoing inguinal lymphadenectomy for the lower extremity melanoma. Conclusion. The inguinal lymphadenectomy with saphenous vein preservation in lower extremity melanoma patients seems to be an oncologically safe procedure and it may offer reduced long-term morbidity. PMID- 25126427 TI - Daytime sleepiness and Parkinson's disease: the contribution of the multiple sleep latency test. AB - Background. Sleep disorders are major nonmotor manifestations of patients with Parkinson's disease (PD), and excessive daytime sleepiness (EDS) is one of the most common symptoms. Objective. We reviewed a current literature concerning major factors that influence EDS in PD patients, using Multiple Sleep Latency Test (MSLT). Methods. A Medline search found 23 studies. Results. The presence of EDS was observed in 12.7% to 47% in patients without complaints of daytime sleepiness and 47% to 66.7% with complaints of daytime sleepiness. Despite being recognized by several authors, major factors that influence EDS, such as severity of motor symptoms, use of dopaminergic medications, and associated sleep disturbances, presented contradictory data. Conclusions. Available data suggest that the variability of the results may be related to the fact that it was conducted with a small sample size, not counting the neuropathological heterogeneity of the disease. Thus, before carrying out longitudinal studies with significant samples, careful analysis should be done by assigning a specific agent on the responsibility of EDS in PD patients. PMID- 25126428 TI - Schwannoma of the tongue in a paediatric patient: a case report and 20-year review. AB - Schwannomas (Neurilemmomas) are benign, encapsulated, slow-growing, and usually solitary tumours originating from Schwann cells of the peripheral nerve sheath with uncertain etiology. Approximately 25-48% of cases are seen in the head and neck region, of which 1% appears in the oral cavity. Lingual schwannoma can affect all age groups with peak incidence between the third and sixth decade. We report a rare case of lingual schwannoma in a 14-year-old girl complaining of asymptomatic swelling over lateral border of tongue since two years. Clinical examination revealed a nodule 1.5 * 1 cm in size, rubbery, nontender, smooth at right lateral border of tongue covered by normal mucosa, with no cervical lymphadenopathy. Excisional biopsy of the lesion was done under local anaesthesia. The histological sections spindle cells with thin wavy nuclei arranged as typical Antoni A (with Verocay bodies) and Antoni B areas. Nuclear palisading distribution (typical of a schwannoma) was readily identifiable. The patient was recurrence-free after one year. PMID- 25126430 TI - Transient global amnesia associated with an acute infarction at the cingulate gyrus. AB - Background. Transient global amnesia (TGA) is a syndrome of sudden, unexplained isolated short-term memory loss. In the majority of TGA cases, no causes can be identified and neuroimaging, CSF studies and EEG are usually normal. We present a patient with TGA associated with a small acute infarct at the cingulate gyrus. Case Report. The patient, a 62 year-old man, developed two episodes of TGA. He had hypertension and hypercholesterolemia. He was found to have an acute ischemic stroke of small size (15 mm of maximal diameter) at the right cerebral cingulate gyrus diagnosed on brain magnetic resonance imaging. No lesions involving other limbic system structures such as thalamus, fornix, corpus callosum, or hippocampal structures were seen. The remainder of the examination was normal. Conclusion. Unilateral ischemic lesions of limbic system structures may result in TGA. We must bear in mind that TGA can be an associated clinical disorder of cingulate gyrus infarct. PMID- 25126429 TI - An Uncommon Presentation of Spontaneous Rectus Sheath Hematoma with Acute Kidney Injury due to Obstructive Uropathy and Prerenal Azotemia. AB - Rectus Sheath Hematoma (RSH) represents an unusual entity which is characterized by acute abdominal pain and tender palpable abdominal mass usually, among elderly patients receiving anticoagulant therapy. We report the case of an 81-year-old woman admitted to our department due to acute abdominal pain and oligoanuria. The patient had recently been hospitalized due to acute myocardial infarction (AMI) and atrial fibrillation (AF) and received both anticoagulant and antiplatelet therapies. The radiological assessments revealed an extended Rectus Sheath Hematoma and bilateral hydronephrosis. Treatment of the hematoma required cessation of anticoagulants and antiplatelet agents, immobilization, blood and fresh frozen plasma transfusion, and administration of vasopressors. The patient recovered gradually and was discharged home fifteen (15) days later. PMID- 25126431 TI - Listerial rhombencephalitis in an immunocompetent woman. AB - Listeriosis usually affects immunocompromised patients including elderly people and pregnant women, but it may also affect otherwise healthy individuals. In our report, we present a case of a rare and very severe form of listeriosis rhombencephalitis in a 61-year-old female with no history of immunosuppression, who, because of history, clinical picture, and laboratory results as well as negative cultures, was at first diagnosed with viral encephalitis. This paper underlines that Listeria monocytogenes infection should be taken into consideration in case of lymphocytic encephalitis even in immunocompetent patients. Typical MRI picture may be crucial in establishing a proper diagnosis as the lab results may be misleading. PMID- 25126432 TI - Disseminated intravascular coagulopathy caused by uterine leiomyoma with sarcoma like findings on magnetic resonance imaging. AB - A leiomyoma rarely causes disseminated intravascular coagulopathy (DIC). In the present report, we describe a case of DIC caused by leiomyoma. A 36-year-old nulliparous woman presented with hypermenorrhea and a lower abdominal mass. On magnetic resonance imaging, we detected a 14 cm uterine tumor, which was suspected to be a sarcoma. Blood tests at the preoperative examination indicated platelet count of 9.6 * 10(4)/MUL, fibrin degradation product level of 107.1 MUg/mL (normal value, 0-5.0 MUg/mL), and fibrinogen level of 54 mg/dL (normal value, 129-271 mg/dL). Based on these findings, we diagnosed the patient with DIC. The patient was treated with nafamostat mesilate and fresh frozen plasma, but the DIC did not show any improvement. Subsequently, a hysterectomy was performed, after which the DIC improved. Clinicopathological findings indicated the presence of a leiomyoma with multiple vessels containing thromboemboli, and suggested that the DIC was caused by the leiomyoma. Therefore, it is essential to consider that that a benign leiomyoma may be a cause of DIC. PMID- 25126433 TI - Ocular trauma from the "knockout game". AB - The "knockout game" is a new form of urban violence receiving much attention in local and national media. Apart from the obvious head trauma, eye injuries may be subtle and overlooked. This report brings awareness of potential eye damage with this type of assault. This report is of a young woman, victim of the knockout game, who sustained a submacular hemorrhage. Beyond a neurologic evaluation for anyone knocked unconscious following the knockout game, patients should be counseled regarding potential ocular injury and encouraged to seek eye care promptly should symptoms develop. PMID- 25126434 TI - An unusual presentation of charcot arthropathy caused by syringomyelia mimicking a soft tissue tumor. AB - Charcot arthropathy is a chronic, degenerative condition and is associated with decreased sensorial innervation. Numerous causes of this arthropathy have been described. Here we report a case of neuropathic arthropathy secondary to syringomyelia which was misdiagnosed as a soft tissue tumor and treated surgically and additionally with radiotherapy at another institution. The patient had clinical and radiological signs of syringomyelia, associated with a limited range of motion, swelling, and pain in the affected joint. Neuropathic arthropathy, although less common, should be considered in cases of unexplained joint swelling, pain, and limited range of motion of the affected joint. PMID- 25126435 TI - Endoscopic CO(2) Laser Horizontal Partial Laryngectomy in Larynx Carcinosarcoma. AB - Background. Carcinosarcoma is an extremely rare malignant neoplasm, with both a malignant epithelial and mesenchymal component, that rarely affects the larynx. Aim. Aim of this paper is to describe the case of a patient affected by a larynx carcinosarcoma treated by endoscopic horizontal partial laryngectomy with CO(2) laser and particularly discuss the histogenetic hypothesis as well as the possible treatment modalities of this rare lesion. Methods. Case report and literature review. Discussion and Conclusion. Still little is known about the biology of carcinosarcoma and there is still no consensus in the literature on the treatment of these tumors. Endoscopic horizontal partial laryngectomy could represent another treatment option in selected cases. PMID- 25126436 TI - Intracranial gliofibroma: a case report and review of the literature. AB - Gliofibroma is a rare tumor with biphasic morphology, commonly occurring in the first two decades of life. Currently, the tumor is not listed as a distinct entity in the current World Health Organization (WHO) classification of central nervous system tumors. As its biological behavior, histogenesis, and prognostic factors are still debated, the aim of this paper was to describe a case of a gliofibroma and to update the data about these lesions. Hence, we present here clinical symptoms, pathological findings, and evolution observed in a child with gliofibroma. A 10-year-old girl with seizures was referred for study. Neuroimaging showed a hemispheric hyperdense tumor with little peritumoral edema and no mass effect. The tumor was totally removed. Histologically, the tumor consisted of a mixture of glial cells and collagen-rich stroma. Immunohistochemical examination revealed positive staining for GFAP, CD 99, S100, and vimentin. EMA staining showed a paranuclear dot pattern in only few cells in isolated areas. These findings of a glial component with collagenous stroma were consistent with a desmoplastic glioma. Because of the rarity of this entity, we believe it is important to report every case in order to adequately analyze and categorize the tumor in the next WHO classification. PMID- 25126437 TI - High-Flow Nasal Cannula Therapy in a Patient with Reperfusion Pulmonary Edema following Percutaneous Transluminal Pulmonary Angioplasty. AB - A 62-year-old woman with Wolff-Parkinson-White syndrome was with recent worsening of dyspnea to New York Heart Association functional status Class III. The patient was diagnosed as having central type chronic thromboembolic pulmonary hypertension. By cardiac catheterization, her mean pulmonary artery pressure was 53 mmHg with total pulmonary resistance 2238 dynes.sec.cm(-5). After medical therapies with tadalafil, furosemide, ambrisentan, beraprost, and warfarin were initiated, percutaneous transluminal pulmonary angioplasty (PTPA) was performed. Following PTPA, life-threating hypoxemia resulting from postoperative reperfusion pulmonary edema developed. High-flow nasal cannula therapy (HFNC) was applied, and 100% oxygen at 50 L/min of flow was required to keep oxygenation. HFNC was continued for 3 days, and the patient was discharged on 8th postoperative day with SpO2 of 97% on 3 L/min of oxygen inhalation. Because of the simplicity of the technique, the lower cost of equipment, and remarkable patient tolerance to the treatment, we speculate that HFNC can take over the post of noninvasive ventilation as first-line therapy for patients with acute respiratory failure. PMID- 25126438 TI - Tuber cinereum diverticula in a 28-month-old with xq21 deletion syndrome. AB - A developmentally delayed 28-month-old male toddler was referred to us for brain MRI. Imaging revealed corpus callosum dysgenesis, forniceal hypoplasia, vermian hypoplasia, and hypothalamic dysmorphism characterized by tuber cinereum diverticula. Subsequent chromosomal microarray showed an Xq21 deletion. We present a case of Xq21 deletion syndrome with midline brain anomalies and a novel hypothalamic malformation. PMID- 25126439 TI - Isolated nasopharyngeal castleman disease: an uncommon diagnosis in an unusual location. AB - Localised nasopharyngeal Castleman disease has rarely been reported. We present a case involving a 23-year-old female, describe the clinical, imaging, and histopathologic features of this challenging diagnosis, and review the literature. PMID- 25126440 TI - Antenatal diagnosis of alobar holoprosencephaly. AB - A twenty-year-old second gravida presented to the department of radiodiagnosis for routine obstetric ultrasound examination. Ultrasonography revealed a live fetus of 17 weeks with absent falx, fused thalami, monoventricle, proboscis, and cyclopia. Fetal MRI was performed and the findings were confirmed. Even though ultrasonography is diagnostic in the detection of fetal anomalies, MRI plays a vital role due to its multiplanar capability and excellent soft tissue resolution. The importance of presenting this classical case of alobar holoprosencephaly is to sensitize the clinicians and radiologists to the imaging manifestations of holoprosencephaly and to stress the importance of early diagnosis. If diagnosed in utero at an early stage of pregnancy, termination can be performed and maternal psychological trauma of bearing a deformed fetus can be avoided. PMID- 25126441 TI - Cecal endometriosis presenting as acute appendicitis. AB - The aim of our paper is to show the diagnosis of Coecal endometriosis as an infrequent reason of right iliac fossa pain. cecal endometriosis manifesting with right lower quadrant pain is difficult to diagnose, and it may even sometimes require laparotomy for diagnosis and treatment. We report here a case of cecal endometriosis causing clinically resembled acute appendicitis. In our patient, a diagnosis of cecal endometriosis was made postoperatively by microscopic examination of excised right colon, and the patient symptoms and general condition were improved after the surgery (open right hemicolectomy and ileocolic anastomosis). PMID- 25126442 TI - Yersinia enterocolitica Infection Simulating Lymphoproliferative Disease, after Liver Transplant. AB - We describe a 14-year-old girl, who was 13 y after liver transplantation for biliary atresia with an unremarkable postoperative course. She presented with fever of up to 40 degrees C, extreme fatigue, malaise, anorexia, and occasional vomiting. On physical examination the only finding was splenomegaly. Lab results showed hyperglobulinemia and an elevated sedimentation rate. Liver function tests were normal except for mild elevation of gammaGTP. Abdominal U/S and CT demonstrated an enlarged spleen with retroperitoneal and mesenteric lymph nodes enlargement. An exhaustive evaluation for infectious causes, autoimmune conditions, and malignancy was negative. A full recovery after 5 months prompted testing for self-limited infectious etiologies. Yersinia enterocolitica infection was diagnosed. PMID- 25126443 TI - Autologous bone marrow mononuclear cells intrathecal transplantation in chronic stroke. AB - Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs) is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM) objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778. PMID- 25126444 TI - Development of the rat model of lapatinib-induced diarrhoea. AB - Targeted therapy of cancer is often associated with clinically significant diarrhoea; however, the mechanisms underpinning this adverse effect are currently unknown. Diarrhoea following treatment with tyrosine kinase inhibitors (TKIs) of EGFR is particularly troublesome. Until recently, understanding of EGFR TKI induced diarrhoea has been limited to clinical observation. However, our group has recently developed the first rat model of EGFR TKI-induced diarrhoea. This paper reviews the published and unpublished findings. PMID- 25126445 TI - Transforming traditional Tai Ji Quan techniques into integrative movement therapy Tai Ji Quan: Moving for Better Balance. AB - Tai Ji Quan, developed as a martial art, has traditionally served multiple purposes, including self-defense, competition/performance, and health promotion. With respect to health, the benefits historically and anecdotally associated with Tai Ji Quan are now being supported by scientific and clinical research, with mounting evidence indicating its potential value in preventing and managing various diseases and improving well-being and quality of life in middle-aged and older adults. The research findings produced to date have both public health significance and clinical relevance. However, because of its roots in the martial arts, transforming traditional Tai Ji Quan movements and training approaches into contemporary therapeutic programs and functional applications is needed to maximize its ultimate utility. This paper addresses this issue by introducing Tai Ji Quan: Moving for Better Balance, a functional therapy that involves the use of Tai Ji Quan principles and Yang-style-based movements to form an innovative, contemporary therapeutic approach that integrates motor, sensory, and cognitive components to improve postural control, gait, and mobility for older adults and those who have neurodegenerative movement impairments. It provides a synergy of traditional and contemporary Tai Ji Quan practice with the ultimate goal of improving balance and gait, enhancing performance of daily functional tasks, and reducing incidence of falls among older adults. PMID- 25126446 TI - Teleoperation System with Hybrid Pneumatic-Piezoelectric Actuation for MRI-Guided Needle Insertion with Haptic Feedback. AB - This paper presents a surgical master-slave tele-operation system for percutaneous interventional procedures under continuous magnetic resonance imaging (MRI) guidance. This system consists of a piezoelectrically actuated slave robot for needle placement with integrated fiber optic force sensor utilizing Fabry-Perot interferometry (FPI) sensing principle. The sensor flexure is optimized and embedded to the slave robot for measuring needle insertion force. A novel, compact opto-mechanical FPI sensor interface is integrated into an MRI robot control system. By leveraging the complementary features of pneumatic and piezoelectric actuation, a pneumatically actuated haptic master robot is also developed to render force associated with needle placement interventions to the clinician. An aluminum load cell is implemented and calibrated to close the impedance control loop of the master robot. A force position control algorithm is developed to control the hybrid actuated system. Teleoperated needle insertion is demonstrated under live MR imaging, where the slave robot resides in the scanner bore and the user manipulates the master beside the patient outside the bore. Force and position tracking results of the master-slave robot are demonstrated to validate the tracking performance of the integrated system. It has a position tracking error of 0.318mm and sine wave force tracking error of 2.227N. PMID- 25126447 TI - Evaluating an Integrative Theoretical Framework for HIV Sexual Risk among Juvenile Justice involved Adolescents. AB - Juvenile justice involved youth are at great risk for negative outcomes of risky sexual behavior including HIV/AIDS. Given the strong connection between alcohol use and risky sex in this population, it is important to consider alcohol use in interventions designed to decrease risky sexual behavior. This paper provides support for an integrative translational model that incorporates psychosocial, neurobiological, and genetic factors to better predict alcohol-related sexual risk behavior. Specifically, we present the design, methods, and baseline data from a complex randomized control trial, Project SHARP (Sexual Health and Adolescent Risk Prevention) in order to illustrate how this broad array of factors can best predict alcohol-related sexual risk behavior. Participants were justice-involved adolescents (n=284) who completed an fMRI and self-report assessments prior to randomization to either a sexual risk plus alcohol risk reduction group intervention or to an information-only contact control group intervention. Structural equation modeling was utilized and findings supported the hypothesized relationships in the translational model. Preliminary data suggest that interventions among justice-involved adolescents targeting alcohol related sexual risk behavior may be more effective if a biopsychosocial approach is considered. PMID- 25126448 TI - Dallas Glaucoma Registry: Preliminary Results. AB - BACKGROUND: Although glaucoma is a leading cause of blindness worldwide, yet there are no large databases where risk factors, current management options and outcomes may be evaluated. With this concept in mind, Dallas Glaucoma Registry was established to focus on an ethnically mixed North Texas population. METHODS: This is a retrospective, chart review of 2,484 patients (4,839 eyes) with glaucoma from three clinics. Data collected included: age, race, gender, intraocular pressure, visual acuity, central corneal thickness, cup-to-disk ratio, extent of visual field damage, glaucoma diagnoses, medical and surgical therapies. RESULTS: The most prevalent glaucoma was primary open angle glaucoma accounting for 44.4% of patients, followed by glaucoma suspect (39.5%), secondary glaucoma (7.2%), angle closure glaucoma (6.8%), normal tension glaucoma (1.7%), and childhood glaucoma (0.5%). The mean (SD) age was 68.7 (13.8) and 41.3% were non Hispanic white, 37.0% were black, 10.4% were Hispanic and 11.3% were of other ethnic origin. Hispanic representation in glaucoma did not match their numbers in general population of North Texas. CONCLUSION: Large numbers of patients in the ongoing Dallas Glaucoma Registry do provide adequate data to better understand risk factors, early detection, improved screening targets, treatment options, outcomes and future studies. PMID- 25126451 TI - Dermatopathology: An abridged compendium of words. A discussion of them and opinions about them. Part 5. PMID- 25126450 TI - A headset method for measuring the visual temporal discrimination threshold in cervical dystonia. AB - BACKGROUND: The visual temporal discrimination threshold (TDT) is the shortest time interval at which one can determine two stimuli to be asynchronous and meets criteria for a valid endophenotype in adult-onset idiopathic focal dystonia, a poorly penetrant disorder. Temporal discrimination is assessed in the hospital laboratory; in unaffected relatives of multiplex adult-onset dystonia patients distance from the hospital is a barrier to data acquisition. We devised a portable headset method for visual temporal discrimination determination and our aim was to validate this portable tool against the traditional laboratory-based method in a group of patients and in a large cohort of healthy controls. METHODS: Visual TDTs were examined in two groups 1) in 96 healthy control participants divided by age and gender, and 2) in 33 cervical dystonia patients, using two methods of data acquisition, the traditional table-top laboratory-based system, and the novel portable headset method. The order of assessment was randomized in the control group. The results obtained by each technique were compared. RESULTS: Visual temporal discrimination in healthy control participants demonstrated similar age and gender effects by the headset method as found by the table-top examination. There were no significant differences between visual TDTs obtained using the two methods, both for the control participants and for the cervical dystonia patients. Bland-Altman testing showed good concordance between the two methods in both patients and in controls. DISCUSSION: The portable headset device is a reliable and accurate method for visual temporal discrimination testing for use outside the laboratory, and will facilitate increased TDT data collection outside of the hospital setting. This is of particular importance in multiplex families where data collection in all available members of the pedigree is important for exome sequencing studies. PMID- 25126449 TI - The determinants of head and neck cancer: Unmasking the PI3K pathway mutations. AB - Studies attempting to identify and understand the function of mutated genes and deregulated molecular pathways in cancer have been ongoing for many years. The PI3K-PTEN-mTOR signaling pathway is one of the most frequently deregulated pathways in cancer. PIK3CA mutations are found 11%-33% of head and neck cancer (HNC). The hotspot mutation sites for PIK3CA are E542K, E545K and H1047R/L. The PTEN somatic mutations are in 9-23% of HNC, and they frequently cluster in the phosphatase domain of PTEN protein. PTEN loss of heterozygosity (LOH) ranges from 41%-71% and loss of PTEN protein expression occurs in 31.2% of the HNC samples. PIK3CA and PTEN are key molecules in the PI3K-PTEN-mTOR signaling pathway. In this review, we provided a comprehensive overview of mutations in the PI3K-PTEN mTOR molecular circuitry in HNC, including PI3K family members, TSC1/TSC2, PTEN, AKT, and mTORC1 and mTORC2 complexes. We discussed how these genetic alterations may affect protein structure and function. We also highlight the latest discoveries in protein kinase and tumor suppressor families, emphasizing how mutations in these families interfere with PI3K signaling. A better understanding of the mechanisms underlying cancer formation, progression and resistance to therapy will inform selection of novel genomic-based personalized therapies for head and neck cancer patients. PMID- 25126453 TI - Acantholytic dyskeratotic acanthoma: case report and review of the literature. AB - BACKGROUND: Focal acantholytic dyskeratosis has been described as an incidental finding and as a clinically distinct lesion. In both situations, a dimorphic histologic pattern is observed: acantholysis and dyskeratosis. Solitary, non genital lesions displaying such pathology have been difficult to classify. Clinical and pathological characteristics of acantholytic dyskeratotic acanthomas are described. METHODS: The features of a patient with solitary, non-genital, acantholytic dyskeratotic acanthoma are presented and the literature on acantholytic dyskeratotic acanthomas is reviewed. Using PubMed the following terms were searched and relevant citations assessed: acantholysis, acanthoma, cutaneous, dyskeratosis, nail, warty. RESULTS: We identified 30 cutaneous acantholytic dyskeratotic acanthomas, including our patient, most often found on the trunk and mimicking basal cell carcinoma, and three subungual acantholytic dyskeratotic acanthomas of the thumb, which mimicked onychopapilloma. CONCLUSION: Acantholytic dyskeratotic acanthomas are clinically and pathologically distinct lesions, which may morphologically present as either truncal plaques or subungual longitudinal erythronychia. PMID- 25126454 TI - Actinic granuloma. PMID- 25126452 TI - The dermatoscopic universe of basal cell carcinoma. AB - Following the first descriptions of the dermatoscopic pattern of basal cell carcinoma (BCC) that go back to the very early years of dermatoscopy, the list of dermatoscopic criteria associated with BCC has been several times updated and renewed. Up to date, dermatoscopy has been shown to enhance BCC detection, by facilitating its discrimination from other skin tumors and inflammatory skin diseases. Furthermore, upcoming evidence suggests that the method is also useful for the management of the tumor, since it provides valuable information about the histopathologic subtype, the presence of clinically undetectable pigmentation, the expansion of the tumor beyond clinically visible margins and the response to non-ablative treatments. In the current article, we provide a summary of the traditional and latest knowledge on the value of dermatoscopy for the diagnosis and management of BCC. PMID- 25126455 TI - Is aggressive digital papillary adenocarcinoma really aggressive digital papillary adenocarcinoma? PMID- 25126457 TI - Multiple primary thick melanomas: similar dermoscopic pattern. PMID- 25126456 TI - Keratoacanthoma versus invasive squamous cell carcinoma: a comparison of dermatoscopic vascular features in 510 cases. AB - INTRODUCTION: Keratoacanthoma (KA) and invasive squamous cell carcinoma (SCC) are keratinocytic tumors displaying vascular features, imaged using dermatoscopy. OBJECTIVE: Compare the dermatoscopy vascular features of KA to SCC. METHODS: This prospective study examined consecutive cases of 100 KA and 410 invasive SCC in a single private practice in Sydney, Australia. Vascular features were recorded in vivo direct from patients using a non-polarized Delta 20 Heine dermatoscope. These vascular features were: linear, branching, serpentine, hairpin, glomerular and dot vessels, the presence or absence of large diameter tumor vessels, vessel presence in central verses peripheral tumor areas and tumor pink areas in different proportions. Following full excision, all cases were submitted for histopathologic diagnosis. RESULTS: Branching vessels were the only vessel morphology that varied, with a significant incidence in KA (25.0%), compared to SCC (10.7%), P < 0.01. Large vessels were identified in 20.0% of KA, compared to 12.4% in SCC, P = 0.05. No vessels were observed in the central tumor areas in 43.4 % of KA compared to 58.0% of SCC, P = 0.01. Other data comparing the central versus peripheral tumor areas for vessels present did not reveal any distinctive associations. There were no significant differences between KA and SCC when reviewing the selected proportions of pink within the tumor. LIMITATIONS: The vascular features may be confounded by tumor depth in KA. Polarized dermatoscopy may not produce the same findings. CONCLUSION: This study found branching vessels to have a higher incidence in KA compared to invasive SCC. Although not statistically significant, large diameter vessels were also more frequent in KA. Proportions of pink within the tumor or central verses peripheral tumor vessel distribution were not useful diagnostic features separating KA from SCC using dermatoscopy. PMID- 25126458 TI - Dermatoscopy of folliculosebaceous cystic hamartoma. AB - A 29-year-old Japanese man presented to our institution with a nodule on his nose that had increased in size since childhood. Physical examination indicated the presence of an elastic, firm, pedunculated red nodule measuring 15 mm in size. Dermatoscopic examination of the nodule indicated a yellowish-white network, yellowish-orange dots/globules at its center, and a pinkish-white structureless peripheral area. Histopathological examination of an excisional biopsy specimen showed a dilated infundibulocystic structure with sebaceous lobules proliferating radially, surrounded by fibrous stroma. Moreover, mature adipocytes and small vessels were noted in the stroma. Based on these histopatho-logic findings, the patient was diagnosed with folliculosebaceous cystic hamartoma. PMID- 25126459 TI - Infundibulocystic basal cell carcinoma: dermoscopic findings and histologic correlation. AB - Infundibulocystic basal cell carcinoma is a rare variant. It was first described in 1987 and proposed as a new basal cell carcinoma (BCC) subtype by Ackerman and Walsh in 1990. Dermoscopy is a noninvasive diagnostic technique that allows prompt identification of many types of BCC. However, dermoscopic findings for the infundibulocystic variant have not been reported. In our patient the dermoscopic findings were maple leaf-like areas in the periphery of the tumor, multiple scattered blue-gray dots and globules, short, fine telangiectasia and chrysalis or white-shiny streaks. All these structures had an underlying anatomopathological correlation. CONCLUSION: According to our case report, dermoscopy findings may aid to clearly diagnose this unusual BCC variant with proper histopathological correlation. PMID- 25126460 TI - Zosteriform cutaneous leishmaniasis diagnosed with the help of dermoscopy. AB - Cutaneous leishmaniasis is usually easy to recognize; however, several atypical features exist, which may pose a diagnostic challenge. Here we report a 55-year old female patient, who presented with an itchy and painful eruption localized in a dermatomal distribution along the right upper chest. Although the clinical appearance of the lesions suggested the diagnosis of herpes zoster, dermoscopic evaluation revealed erythema, hyperkeratosis, burst star whitish appearance and hairpin vessels, compatible with the diagnosis of cutaneous leishmaniasis. Indeed, leishmania amastigotes were detected by smear from the lesions. Zosteriform presentation of cutaneous leishmaniasis, as exemplified by our patient, is especially rare. In our case dermoscopy has proven to be an accessible and easy tool to diagnose such atypical presentation of cutaneous leishmaniasis, and dermatologists in endemic areas should be familiar with its typical dermoscopic features. PMID- 25126461 TI - The dermoscopic variability of Degos disease at different stages of progression. PMID- 25126462 TI - Melanoma and satellite blue papule. AB - The colors that are seen in dermoscopy depend on the anatomic level of the skin at which the chromophores are seen. Blue color can be found in a variety of melanocytic and nonmelanocytic lesions. An 89-year-old man presented with a 3 year history of a slow-growing, hyperpigmented patch located on the distal third of the right arm. Dermoscopy showed an atypical network, irregularly distributed globules, pigmented internal streaks and a milky-red area. Based on these findings a diagnosis of slow-growing malignant melanoma was made. Simultaneously, a well-defined blue papule was seen on the proximal third of the same arm. Dermoscopy disclosed a homogeneous blue pattern. After clinical and dermoscopic correlation our differential diagnosis for this blue lesion included cutaneous melanoma metastasis, blue nevus and foreign body reaction. The patient recalled its onset 75 years ago after a grenade explosion. We also discuss the blue lesion appearance under reflectance confocal microscopy and high-definition optical coherence tomography. Histopathological examination after excision of the hyperpigmented patch and blue papule revealed a melanoma in situ and a foreign body reaction, respectively. The diagnostic evaluation of a blue lesion should always rely on the integration of all data, especially clinical and dermoscopic features. Other non-invasive techniques, like reflectance confocal microscopy and high-definition optical coherence tomography can also be important aids for its differential diagnosis. PMID- 25126463 TI - Recognizing the benefits and pitfalls of reflectance confocal microscopy in melanoma diagnosis. PMID- 25126464 TI - Dermatoscopy: A multicolored lesion on the forehead. PMID- 25126465 TI - An atypical pigmented lesion-Answer. PMID- 25126466 TI - Application of black salve to a thin melanoma that subsequently progressed to metastatic melanoma: a case study. AB - This is a case study of a female patient diagnosed with superficial spreading melanoma who decided to treat the lesion by the application of a preparation known as black salve. Persistence of the melanoma was documented five years later with subsequent evidence of metastatic spread to the regional lymph nodes, lungs, liver, subcutaneous tissues and musculature. A literature search has revealed one other case study of the use of black salve for the treatment of melanoma. PMID- 25126467 TI - "Neglected nipples": acanthosis nigricans-like plaques caused by avoidance of nipple cleansing. AB - BACKGROUND: Acanthosis nigricans (AN) develops sporadically or in association with obesity, insulin-resistance and dark pigmentary phenotype. Unusual clinical presentations of AN may be diagnostically vexing. OBJECTIVES: The aim of the report is to present unusual clinical and dermoscopic pictures of hyper keratotic, brownish lesions of the nipples resembling acanthosis nigricans. PATIENTS/METHODS: Data including clinical and dermoscopic features of two patients with the "neglected nipples": acanthosis nigricans-like (AN-like) hyperpigmented plaques caused by avoidance of nipple cleansing. RESULTS: Beside the anamnestic clue, presentation of AN-like plaques in the "neglected nipples" is limited to the breasts, in the absence of involvement of other flexural sites classically affected by AN. Dermoscopy aids the exclusion of a tumor, as it reveals exclusively structureless, brown-gray-black hyperkeratosis in the absence of criteria associated with melanocytic or non-melanocytic skin neoplasms of the nipple. The "neglected breasts" are easily treated by keratolytic creams and hygiene. CONCLUSIONS: The "neglected nipples" condition, presenting as bilateral AN-like papules and plaques of the nipples, is due to avoidance of cleansing of the nipple area, resulting in accumulation of keratotic cellular debris. PMID- 25126468 TI - A dermoscope allowing the use of surgical light as illumination. PMID- 25126469 TI - Cutis marmorata telangiectatica congenita restricted to both breasts in a young female. AB - Cutis marmorata telangiectatica congenita (CMTC) is a very rarely occurring congenital disorder with persistent cutis marmorata, telangiectasia, and phlebectasia. This disorder may be associated with cutaneous atrophy and ulceration of the involved skin. We herewith report a 20-year-old female patient with CMTC since childhood along with ulcerations on both breasts. CMTC is a benign vascular anomaly presenting with dilatation of capillaries and veins of dermis and is apparent at birth. The patient had reticulated bluish-purple skin changes over both breasts. Although it resembled physiological cutis marmorata, it was more pronounced and definitely was unvarying and permanent in pattern. A variety of vascular malformations have been described along with this disorder. Etiology is not very clear; it may be multifactorial in origin. Prognosis in uncomplicated cases is good. PMID- 25126470 TI - Uncommon presentations of tinea versicolor. AB - Tinea versicolor (TV) is a common cutaneous fungal infection characterized by superficial scaling and a mild disturbance of skin pigmentation. It typically affects the chest, upper back, and shoulders. However, involvement of more unusual regions of the body such as the face and scalp, arms and legs, intertriginous sites, genitalia, areolae, and palms and soles has been reported. This report details two such cases observed at our institution: a 32-year-old woman with involvement of the popliteal fossa and a 16-year-old boy with involvement of the groin. The clinician must be aware of these variations in location and perform the appropriate diagnostic workup when lesions have the characteristic morphology of TV despite an unusual location. The etiology, pathophysiology, and epidemiology of TV are reviewed and current literature describing other instances of TV in uncommon locations is discussed. PMID- 25126471 TI - Letter to the editor. PMID- 25126473 TI - The Topical Evolution: Free Ions, Orthomolecular Agents, Phytochemicals, and Insect-Produced Substances. AB - Significance: A variety of topical antiseptic substances have been used historically to treat open wounds with suspected tissue infection or that are slow to heal. However, the effectiveness of these substances in treating infected or recalcitrant wounds remains controversial. Recent Advances: Newly formulated topical antiseptics delivered through differing dressing technologies, such as ionic substances, hold the potential to limit the development of and treat antibiotic-resistant microbes in open wounds. Other topically delivered substances, such as insect-derived substances, orthomolecular agents, and phytochemicals, also present opportunities to optimize wound healing by decreasing tissue bioburden and facilitating the wound healing process. Critical Issues: Limited systemic perfusion of open wounds in individuals with certain diagnoses, such as peripheral arterial disease or necrotizing infection and the increasing number of antibiotic-resistant wound pathogens, suggests a continued role for topically applied antiseptic agents. Likewise, the failure of wounds to heal when treated with standard of care therapy opens the door to innovative treatment approaches that include the natural substances described in this article. Future Directions: Evidence for the use of select topical antiseptic agents from each of the aforementioned categories will be discussed in this article. Additional well-controlled clinical studies are needed to provide definitive recommendations for many of these topical agents. PMID- 25126474 TI - What Do Patients Want? Patient Preference in Wound Care. AB - Patient preferences are statements made or actions taken by consumers that reflect their desirability of a range of health options. The concept occupies an increasingly prominent place at the center of healthcare reform, and is connected to all aspects of healthcare, including discovery, research, delivery, outcome, and payment. Patient preference research has focused on shared decisions, decisional aids, and clinical practice guideline development, with limited study in acute and chronic wound care populations. The wound care community has focused primarily on patient focused symptoms and quality of life measurement. With increasing recognition of wound care as a medical specialty and as a public health concern that consumes extensive resources, attention to the preferences of end-users with wounds is necessary. This article will provide an overview of related patient-centered concepts and begin to establish a framework for consideration of patient preference in wound care. PMID- 25126475 TI - Collect Data, Tell Stories: Utilizing Available Data to Improve Wound Product Selection, Reduce Costs, and Improve Outcomes. AB - Objective: To develop a tool to assist in the evaluation of treatment options based on clinically relevant parameters, thus enabling clinicians to heal patients more efficiently. Approach: Outlined here is the prototypic model of a comprehensive analysis tool to compare products by category, accounting for product characteristics, effectiveness data from literature, costs, and patient needs or clinician preferences. Results: The tool is demonstrated with a venous leg ulcer example, and ideas for expanding the tool in the future are provided. Innovation: Although this is a simple model, the authors believe that it provides a valid and useful platform for comparing similar products of a given type using available information and reflecting real-world use to give a practical approach to clinical decision-making. Conclusion: Future funding for comprehensive, comparative effectiveness studies should provide clarity on which products to choose for specific applications. Meanwhile, tools like this can provide guidance, and can be modified to accommodate varying circumstances. PMID- 25126476 TI - A Global Perspective on Wound Care. AB - The development of an interprofessional team approach to the care of acute and chronic wounds is a worldwide challenge. This global unmet need has recently been recognized by the World Health Organization (WHO) and addressed by the Association for the Advancement of Wound Care (AAWC) Global Volunteers program. This article provides an overview of the escalating international wound problem. Current programs established to deal with wounds in resource-poor countries are presented as well as information on volunteering. PMID- 25126472 TI - Wound Dressings and Comparative Effectiveness Data. AB - Significance: Injury to the skin provides a unique challenge, as wound healing is a complex and intricate process. Acute wounds have the potential to move from the acute wound to chronic wounds, requiring the physician to have a thorough understanding of outside interventions to bring these wounds back into the healing cascade. Recent Advances: The development of new and effective interventions in wound care remains an area of intense research. Negative pressure wound therapy has undoubtedly changed wound care from this point forward and has proven beneficial for a variety of wounds. Hydroconductive dressings are another category that is emerging with studies underway. Other modalities such as hyperbaric oxygen, growth factors, biologic dressings, skin substitutes, and regenerative materials have also proven efficacious in advancing the wound healing process through a variety of mechanisms. Critical Issues: There is an overwhelming amount of wound dressings available in the market. This implies the lack of full understanding of wound care and management. The point of using advanced dressings is to improve upon specific wound characteristics to bring it as close to "ideal" as possible. It is only after properly assessing the wound characteristics and obtaining knowledge about available products that the "ideal" dressing may be chosen. Future Directions: The future of wound healing at this point remains unknown. Few high-quality, randomized controlled trials evaluating wound dressings exist and do not clearly demonstrate superiority of many materials or categories. Comparative effectiveness research can be used as a tool to evaluate topical therapy for wound care moving into the future. Until further data emerge, education on the available products and logical clinical thought must prevail. PMID- 25126477 TI - Medicare Payment: Surgical Dressings and Topical Wound Care Products. AB - Medicare patients' access to surgical dressings and topical wound care products is greatly influenced by the Medicare payment system that exists in each site of care. Qualified healthcare professionals should consider these payment systems, as well as the medical necessity for surgical dressings and topical wound care products. Scientists and manufacturers should also consider these payment systems, in addition to the Food and Drug Administration requirements for clearance or approval, when they are developing new surgical dressings and topical wound care products. Due to the importance of the Medicare payment systems, this article reviews the Medicare payment systems in acute care hospitals, long-term acute care hospitals, skilled nursing facilities, home health agencies, durable medical equipment suppliers, hospital-based outpatient wound care departments, and qualified healthcare professional offices. PMID- 25126478 TI - Preconditioning stem cells for in vivo delivery. AB - Stem cells have emerged as promising tools for the treatment of incurable neural and heart diseases and tissue damage. However, the survival of transplanted stem cells is reported to be low, reducing their therapeutic effects. The major causes of poor survival of stem cells in vivo are linked to anoikis, potential immune rejection, and oxidative damage mediating apoptosis. This review investigates novel methods and potential molecular mechanisms for stem cell preconditioning in vitro to increase their retention after transplantation in damaged tissues. Microenvironmental preconditioning (e.g., hypoxia, heat shock, and exposure to oxidative stress), aggregate formation, and hydrogel encapsulation have been revealed as promising strategies to reduce cell apoptosis in vivo while maintaining biological functions of the cells. Moreover, this review seeks to identify methods of optimizing cell dose preparation to enhance stem cell survival and therapeutic function after transplantation. PMID- 25126479 TI - Combinatorial fibronectin and laminin signaling promote highly efficient cardiac differentiation of human embryonic stem cells. AB - Cardiomyocytes (CMs) differentiated from human embryonic stem cells (hESCs) are a promising and potentially unlimited cell source for myocardial repair and regeneration. Recently, multiple methodologies-primarily based on the optimization of growth factors-have been described for efficient cardiac differentiation of hESCs. However, the role of extracellular matrix (ECM) signaling in CM differentiation has not yet been explored fully. This study examined the role of ECM signaling in the efficient generation of CMs from both H7 and H9 ESCs. The hESCs were differentiated on ECM substrates composed of a range of fibronectin (FN) and laminin (LN) ratios and gelatin and evaluated by the fluorescence activated cell scanning (FACS) analysis on day 14. Of the ECM substrates examined, the 70:30 FN:LN reproducibly generated the greatest numbers of CMs from both hESC lines. Moreover, the LN receptor integrin beta4 (ITGB4) and FN receptor integrin beta5 (ITGB5) genes, jointly with increased phosphorylated focal adhension kinase and phosphorylated extracellular signal-regulated kinases (p-ERKs), were up-regulated over 13-fold in H7 and H9 cultured on 70:30 FN:LN compared with gelatin. Blocking studies confirmed the role of all these molecules in CM specification, suggesting that the 70:30 FN:LN ECM promotes highly efficient differentiation of CMs through the integrin-mediated MEK/ERK signaling pathway. Lastly, the data suggest that FN:LN-induced signaling utilizes direct cell-to-cell signaling from distinct ITGB4(+) and ITGB5(+) cells. PMID- 25126480 TI - Directing human induced pluripotent stem cells into a neurosensory lineage for auditory neuron replacement. AB - Emerging therapies for sensorineural hearing loss include replacing damaged auditory neurons (ANs) using stem cells. Ultimately, it is important that these replacement cells can be patient-matched to avoid immunorejection. As human induced pluripotent stem cells (hiPSCs) can be obtained directly from the patient, they offer an opportunity to generate patient-matched neurons for transplantation. Here, we used an established neural induction protocol to differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell line (hESC; H9) toward a neurosensory lineage in vitro. Immunocytochemistry and qRT-PCR were used to analyze the expression of key markers involved in AN development at defined time points of differentiation. The hiPSC- and hESC derived neurosensory progenitors expressed the dorsal hindbrain marker (PAX7), otic placodal marker (PAX2), proneurosensory marker (SOX2), ganglion neuronal markers (NEUROD1, BRN3A, ISLET1, betaIII-tubulin, Neurofilament kDa 160), and sensory AN markers (GATA3 and VGLUT1) over the time course examined. The hiPSC- and hESC-derived neurosensory progenitors had the highest expression levels of the sensory neural markers at 35 days in vitro. Furthermore, the neurons generated from this assay were found to be electrically active. While all cell lines analyzed produced functional neurosensory-like progenitors, variabilities in the levels of marker expression were observed between hiPSC lines and within samples of the same cell line, when compared with the hESC controls. Overall, these findings indicate that this neural assay was capable of differentiating hiPSCs toward a neurosensory lineage but emphasize the need for improving the consistency in the differentiation of hiPSCs into the required lineages. PMID- 25126481 TI - Establishment and characterization of a singaporean chinese lung adenocarcinoma cell line with four copies of the epidermal growth factor receptor gene. AB - We have established a lung adenocarcinoma cell line, ETCC016, from lung pleural effusion of a male Singaporean Chinese with advanced lung adenocarcinoma. The subject smoked 20 cigarettes per day for more than 30 years. The cell line arose from spontaneous transformation of cells grown in a collagen-coated culture dish. Transformed characteristics of the cell line include the ability to reach high confluency in a culture dish, low cell doubling time, ability to form colonies in soft agar, and ability to form solid tumor in immune-compromised SCID mice. Immunostaining showed that the cells originated from lung epithelial cells. Genomic analysis revealed a large amount of chromosomal aberrations (gain and loss of genetic materials, and loss of heterozygosity [LOH]), indicative of a long history of smoking. The cells have four copies of epidermal growth factor receptor (EGFR) and three copies of MYC, but have lost one copy of the RB1 gene. LOH was detected in TP53 and BRAF genes. There is no anaplastic lymphoma kinase (ALK) gene rearrangement. The ETCC016 lung adenocarcinoma cell line has demonstrated susceptibility towards inhibitors specific for EGFR/HER2 and ALK targets, but resistance to MYC-specific inhibitor. This cell line will be a useful model for further understanding of lung adenocarcinoma. PMID- 25126482 TI - A moderate increase of hydrogen peroxide level is beneficial for spontaneous resumption of meiosis from diplotene arrest in rat oocytes cultured in vitro. AB - Hydrogen peroxide (H2O2) acts as a signaling molecule and modulates various aspects of cell functions in a wide variety of cells including mammalian germ cells. We examined whether a decreased level of intra-oocyte cyclic 3',5' adenosine monophosphate (cAMP) leads to accumulation of H2O2, and if so, whether a moderate increase of H2O2 inactivates maturation promoting factor (MPF) during spontaneous resumption of meiosis in rat oocytes cultured in vitro. Removal of cumulus cells and culture of denuded oocytes in vitro significantly decreased oocyte cAMP level and led to spontaneous meiotic resumption from diplotene arrest. The reduced oocyte cAMP level was associated with an increased oocyte H2O2 level and reduced catalase activity. Exogenous supplementation of H2O2 induced meiotic resumption from diplotene arrest in a concentration- and time dependent manner in oocytes treated with 0.1 mM of 3-isobutyl-1-methylxanthine, while dibutyryl-cAMP and 3-t-butyl-4-hydroxyanisole inhibited the stimulatory effect of exogenous H2O2. The increased intra-oocyte H2O2 level induced Thr 14/Tyr-15 phosphorylation of CDK1, while Thr-161 phosphorylated CDK1 and cyclin B1 levels were reduced significantly. These results suggest that a decreased level of intra-oocyte cAMP is associated with an increased level of H2O2. The increased level of H2O2 was associated with high phosphorylation of Thr-14/Tyr-15 and dephosphorylation of the Thr-161 residue of CDK1 and reduced the cyclin B1 level, which eventually inactivated MPF. The MPF inactivation triggered spontaneous resumption of meiosis from diplotene arrest in rat oocytes cultured in vitro. PMID- 25126483 TI - High resolution x-ray: a reliable approach for quantifying osteoporosis in a rodent model. AB - Osteoporosis is the most common metabolic disease of bone, resulting in significant worldwide morbidity. Currently, there are insufficient imaging modalities available to evaluate osteoporotic bones in small animal models. Here, we demonstrate the feasibility of using high resolution X-ray imaging as a comparable measure of bone degeneration to dual-energy X-ray absorptiometry (DXA) in an osteoporosis rodent model. At week 0, animals underwent either an ovariectomy (OVX) or sham procedure (SHAM). DXA analysis was performed weekly to confirm and compare the bone degenerative changes induced by OVX. A comparison using high resolution X-ray imaging (Faxitron((r))) was then performed postmortem due to need of soft tissue removal. Two regions of interest (ROIs) were utilized: the distal third of the femur and the lumbar spine (L4/L5). It was observed that SHAM animals maintained a relatively constant bone mineral density (BMD), in comparison to OVX animals, whereby a significant decrease in BMD was appreciated. Post mortem X-ray scans were performed and converted to 8-bit color and quantified. A high level of agreement with DXA quantifications was observed with X-ray quantifications, and a significant correlation between the radiopacity, visualized by color distributions, and the DXA BMD values between animal groups was evident. Our study demonstrates the applicability of high resolution X-ray imaging both qualitatively and quantitatively as a reliable approach for quantifying osteoporosis in rodent osteoporotic models. With DXA being a highly user dependent modality, our technique is a unique secondary methodology to verify DXA findings and minimize inter-observer variability. PMID- 25126484 TI - Prosthetic valve endocarditis due to Streptococcus pneumoniae. AB - INTRODUCTION: In the pre-antibiotic era up 10% of cases of infective endocarditis were due to Streptococcus pneumoniae, but this association is currently exceedingly rare. CASE DESCRIPTION: Since 1997 we have diagnosed three patients, all aged >70, with endocarditis due to S. pneumoniae. One of these three cases involved a prosthetic valve, another a prosthetic ring. All three patients completely recovered with antibiotic treatment only. DISCUSSION AND EVALUATION: During the same period there were 1694 cases of pneumococcal bacteremia, of whom 395 (23%) after age 70. Therefore, after age 70 the prevalence of endocarditis out of all cases of pneumococcal bacteremia was 0.7%. A literature review detected another 16 cases of pneumococcal PVE. The mean age of these 17 patients was 64+/-14; 10 were female and 7 male. In most instances, symptom duration was short, < 6 days. Valve surgery was performed in 5 cases (29%) and 13 patients (76%) survived. CONCLUSIONS: Endocarditis due to S. pneumoniae is rare in the antibiotic era; even in patients with prosthetic valves its course is evidently not more virulent than with other low-virulent organisms. PMID- 25126485 TI - The association in a two-way contingency table through log odds ratio analysis: the case of Sarno river pollution. AB - In this paper we are proposing a general framework for the analysis of the complete set of log Odds Ratios (ORs) generated by a two-way contingency table. Starting from the RC (M) association model and hypothesizing a Poisson distribution for the counts of the two-way contingency table we are obtaining the weighted Log Ratio Analysis that we are extending to the study of log ORs. Particularly we are obtaining an indirect representation of the log ORs and some synthesis measures. Then for studying the matrix of log ORs we are performing a generalized Singular Value Decomposition that allows us to obtain a direct representation of log ORs. We also expect to get summary measures of association too. We have considered the matrix of complete set of ORs, because, it is linked to the two-way contingency table in terms of variance and it allows us to represent all the ORs on a factorial plan. Finally, a two-way contingency table, which crosses pollution of the Sarno river and sampling points, is to be analyzed to illustrate the proposed framework. PMID- 25126486 TI - Genetic fragmentation in India's third longest river system, the Narmada. AB - India's third longest river, the Narmada, is studied here for the potential effects on native fish populations of river fragmentation due to various barriers including dams and a waterfall. The species we studied include a cyprinid fish, Catla catla, and a mastacembelid, Mastacembelus armatus, both of which are found in the Narmada. Our goal was to use DNA sequence information from the D-loop region of the mitochondrial DNA to explore how this fragmentation could impact the genetic structure of these fish populations. Our results clearly show that these barriers can contribute to the fragmentation of the genetic structure of these fish communities, Furthermore, these barriers enhance the effects of natural isolation by distance and the asymmetry of dispersal flows. This may be a slow process, but it can create significant isolation and result in genetic disparity. In particular, populations furthest upstream having low migration rates could be even more subject to genetic impoverishment. This study serves as a first report of its kind for a river system on the Indian subcontinent. The results of this study also emphasize the need for appropriate attention towards the creation of fish passages across the dams and weirs that could help in maintaining biodiversity. PMID- 25126488 TI - Rare aggressive natural killer cell leukemia presented with bone marrow fibrosis a diagnostic challenge. AB - Aggressive natural killer cell leukemia is an extraordinary rare aggressive malignant neoplasm of natural killer cells. Although its first recognition as a specific entity was approximately 20 years ago, this leukemia has not yet been satisfactorily characterized as fewer than 200 cases have been reported in the literature and up to our knowledge, this is the first case report in Qatar. Reaching a diagnosis of aggressive natural killer leukemia was a challenging experience, because in addition to being a rare entity, the relative scarcity of circulating neoplastic cells, failure to obtain an adequate aspirate sample sufficient to perform flow cytometric analysis, together with the absence of applicable method to prove NK clonality (as it lack specific clonal marker); our case had atypical confusing presentation of striking increase in bone marrow fibrosis that was misleading and complicated the case further. The bone marrow fibrosis encountered may be related to the neoplastic natural killer cells' chemokine profile and it may raise the awareness for considering aggressive natural killer leukemia within the differential diagnosis of leukemia with heightened marrow fibrosis. PMID- 25126487 TI - Evaluation of industrial dairy waste (milk dust powder) for acetone-butanol ethanol production by solventogenic Clostridium species. AB - Readily available inexpensive substrate with high product yield is the key to restoring acetone-butanol-ethanol (ABE) fermentation to economic competitiveness. Lactose-replete cheese whey tends to favor the production of butanol over acetone. In the current study, we investigated the fermentability of milk dust powder with high lactose content, for ABE production by Clostridium acetobutylicum and Clostridium beijerinckii. Both microorganisms produced 7.3 and 5.8 g/L of butanol respectively, with total ABE concentrations of 10.3 and 8.2 g/L, respectively. Compared to fermentation with glucose, fermentation of milk dust powder increased butanol to acetone ratio by 16% and 36% for C. acetobutylicum and C. beijerinckii, respectively. While these results demonstrate the fermentability of milk dust powder, the physico-chemical properties of milk dust powder appeared to limit sugar utilization, growth and ABE production. Further work aimed at improving the texture of milk dust powder-based medium would likely improve lactose utilization and ABE production. PMID- 25126489 TI - Expressive aphasia in a patient with chronic myelomonocytic leukemia. AB - Various paraneoplastic autoimmune phenomena have been reported in patients with myelodysplastic syndromes. We describe a patient who developed expressive aphasia as a paraneoplastic complication of chronic myelomonocytic leukemia (CMML). Awareness of the various possible manifestations of CMML may aid in the early recognition of the condition. PMID- 25126490 TI - Non-high-density lipoprotein cholesterol (non-HDL-C) levels in children with nonalcoholic fatty liver disease (NAFLD). AB - Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular disease (CVD) risk in children. Non-high density lipoprotein cholesterol (non-HDL-C) has been shown to be a good predictor of cardiovascular events. Recent data in adults found non-alcoholic steatohepatitis (NASH) to be associated with significantly higher levels of non-HDL-C than simple steatosis, suggestive it might be used as a non-invasive tool to diagnose NASH. The goal of our study was to assess non-HDL-C levels in children with NAFLD. Our cohort consisted of pediatric patients with biopsy-proven NAFLD. Anthropometric, laboratory, and histologic data were obtained on all patients. Univariable analysis was performed to assess differences in clinical characteristics between groups. Spearman rank correlation coefficients were calculated to assess the correlation between non-HDL-C levels and clinical variables. ANCOVA was used to adjust for possible confounders. 302 subjects with NAFLD were included in our study; 203 with NASH and 99 without NASH. Subjects with NASH had significantly higher non-HDL-C levels than those without (p = 0.004). Histologic features of NASH, including ballooning, inflammation, and fibrosis were found to be weakly correlated with non-HDL-C levels, (p < 0.05 for all). After adjusting for the presence of metabolic syndrome (MetS), ALT, and GGT, the association between non HDL-C and NASH was not significant (p = 0.66). In Conclusion, non-HDL-C levels are higher in children with NASH than those with simple steatosis, suggesting increased CVD risk. This may be a reflection of the higher prevalence of MetS. Non-HDL-C had a positive association with histologic features of NASH. PMID- 25126491 TI - Personalized medicine approach in mycobacterial disease. AB - Mycobacterial diseases are a group of illnesses that cause a considerable number of deaths throughout the world, regardless of years of public health control efforts. Personalized medicine is a new but rapidly advancing field of healthcare. Personalized medicine in the field of mycobacteriology may be applied in the different levels of management such as prevention, diagnosis, treatment and prognosis. A genetic predisposition and a protein dysfunction study are recommended to tailor an individual approach in mycobacterial diseases. PMID- 25126492 TI - Arthroscopically confirmed femoral button deployment. AB - The anterior cruciate ligament TightRope RT (Arthrex, Naples, FL) is a graft suspension device for cruciate ligament reconstruction. It is an adjustable length graft loop cortical fixation device designed to eliminate the requirement for loop length calculation and to facilitate complete graft fill of short femoral sockets that are common with anatomic anterior cruciate ligament placement. The adjustable loop length means "one size fits all," thus removing the need for multiple implant sizes and allowing graft tensioning even after fixation. However, the device has been associated with the same complications that have been described with EndoButton (Smith & Nephew Endoscopy, Andover, MA) fixation. The button of the TightRope RT may remain in the femoral tunnel rather than flipping outside of the tunnel to rest on the lateral femoral cortex, or it may become jammed inside the femoral canal. Conversely, the button may be pulled too far off the femoral cortex into the overlying soft tissue and flip in the substance of the vastus lateralis. We describe a new and simple arthroscopic technique to directly visualize the deployment and seating of the TightRope button on the lateral cortex of the femur to avoid all the aforementioned complications. PMID- 25126493 TI - An augmentation suture technique for arthroscopic rotator cuff repair. AB - The double-row suture technique and the suture-bridge technique have been used for rotator cuff repair to decrease the occurrence of retears. However, when only the degenerated tendon end is sutured, the risk of retear remains. The augmentation suture technique is a new procedure that connects the intact medial tendon to the lateral greater tuberosity, and this approach may protect the initial repair site. The procedures for this technique are as follows: 2 sutures are placed through the medial intact tendon, the cuff tear is repaired by the single-row technique, 2 sutures are pulled laterally over the single-row repair site, and 2 sutures are fixed at the lateral greater tuberosity with a push-in type anchor. This technique is simple and easy and does not require special equipment. Moreover, this approach can augment the single-row repair technique without creating high tension at the cuff end. PMID- 25126494 TI - Retrograde synovial biopsy of the knee joint using a novel biopsy forceps. AB - Synovial biopsies of the knee joint are commonly performed arthroscopically with the patient under full or regional anesthesia. To overcome the effort, costs, and potential risks of surgery, we developed an office-based technique for retrograde synovial biopsy using a designated novel biopsy forceps. Using this technique, no arthroscopic or radiologic control is needed to perform rapid synovial biopsies of the knee joint. Concomitant aspiration of synovial fluid can be performed. A technical description of the procedure is given. PMID- 25126495 TI - Hamstring graft preparation using a modified rolling hitch technique. AB - Anterior cruciate ligament reconstruction using double-looped hamstring autograft is a common procedure in orthopaedic practice. However, during placement of the running, locking stitches at each end of the harvested tendons, the surgeon may face several potential obstacles, including the risk of damaging the tendon, predisposing the surgeon to needle-stick injury, and extended time consumption. We report a modified rolling hitch technique for hamstring graft preparation that is quick, cost-saving, and needleless as an alternative method. The original rolling hitch technique uses a traditional knot that attaches a rope to an object; the modified rolling hitch technique was created by adding 1 more turn before finishing with a half-hitch, which may prevent suture slippage off the tendon, thus providing sufficient fixation of the suture-tendon construct. PMID- 25126496 TI - Minimally invasive reconstruction of the medial patellofemoral ligament using quadriceps tendon. AB - Reconstruction of the medial patellofemoral ligament (MPFL) for the treatment of patellar instability has received increased attention over the past few years. Most operative techniques use hamstring grafts fixed with bone tunnels and/or anchors on the patella. Despite good clinical results using these techniques, complications such as implant breakage, patellar fractures through bone tunnels, and loss of knee motion have occurred. We present a minimally invasive technique for MPFL reconstruction using a strip of quadriceps tendon. With the use of specially designed instruments, the graft is harvested through a 3-cm transverse incision at the proximal pole of the patella. The tendon strip is then dissected distally on the patella, left attached, and diverged 90 degrees medially underneath the medial prepatellar tissue. The graft is fixed on the femur in 20 degrees of knee flexion in a bone tunnel with a bioabsorbable interference screw (adults) or a bone anchor (children). We think that this technique presents a valuable alternative to common hamstring techniques for primary MPFL reconstruction in children and adults, as well as for MPFL revision surgery. PMID- 25126497 TI - Arthroscopic excision of bone fragments in a neglected fracture of the lateral process of the talus in a junior soccer player. AB - Fractures of the lateral process of the talus are uncommon and often overlooked. Typically, they are found in adult snowboarders. We report the case of an 11-year old male soccer player who complained of lateral ankle pain after an inversion injury 6 months earlier. He did not respond to conservative treatment and thus underwent arthroscopic excision of fragments of the talar lateral process. The ankle was approached through standard medial and anterolateral portals. A 2.7-mm diameter 30 degrees arthroscope was used. Soft tissues around the talus were cleared with a motorized shaver, and the lateral aspect of the talar process was then visualized. The lateral process presented as an osseous overgrowth, and a loose body was impinged between the talus and the calcaneus. The osseous overgrowth was resected piece by piece with a punch, and the loose body was removed en block. The patient returned to soccer 5 weeks after the operation. This case exemplifies 2 important points: (1) This type of fracture can develop even in children and not only in snowboarders. (2) Arthroscopic excision of talar lateral process fragments can be accomplished easily, and return to sports can be achieved in a relatively short time. PMID- 25126498 TI - Pediatric anterior cruciate ligament femoral fixation: the trans-iliotibial band endoscopic portal for direct visualization of ideal button placement. AB - Pediatric and adolescent anterior cruciate ligament reconstruction is a commonly performed procedure that has been increasing in incidence. Multiple techniques for graft fixation have been described. Button-based femoral cortical suspension fixation of the anterior cruciate ligament graft allows for fast, secure fixation with strong load-to-failure biomechanical properties. The biomechanical properties of button-based femoral cortical suspension fixation are especially beneficial with soft-tissue grafts such as hamstring autografts. Confirmation of a successfully flipped button can be achieved with intraoperative fluoroscopy or indirect viewing; however, these techniques do not provide direct visualization of the flipped button. Our trans-iliotibial band endoscopic portal allows the surgeon to safely and directly visualize the flipped button on the lateral femoral cortex and ensure that there is no malpositioning in the form of an incompletely flipped button or from soft-tissue interposition between the button and the lateral femoral cortex. This portal therefore allows for direct visual confirmation that the button is fully flipped and resting flush against the femoral cortex, deep to the iliotibial band and vastus lateralis. PMID- 25126499 TI - Arthroscopic delivery of cancellous tibial autograft for unstable osteochondral lesions in the adolescent knee. AB - The appropriate surgical technique for the treatment of unstable osteochondral lesions of the knee remains unclear and had been traditionally described with an open arthrotomy. Administration of bone grafting material in the knee may be performed for a variety of pathologic conditions, including unstable osteochondritis dissecans, traumatic osteochondral defects, or subchondral fracture nonunion, or for preparation of residual tunnels during revision anterior cruciate ligament reconstruction. Although various grafting materials have been described in the literature, cancellous autograft remains the gold standard for treatment safety and efficacy. We describe a successful technique for arthroscopic delivery of autogenous bone graft during fixation of unstable osteochondral lesions of the knee. When the indication for grafting is established, cancellous autograft is harvested from the proximal tibia, undergoes morcellation, and is soaked in bone marrow aspirate obtained through the harvest window. The bone graft is then packed into a modified tuberculin syringe. After arthroscopic preparation of the unstable osteochondral fragment and the respective donor surface, the tuberculin syringe is placed through a standard arthroscopy portal and the bone graft is introduced into the defect under direct visualization, followed by an appropriate osteochondral fixation technique. PMID- 25126500 TI - The golf ball sign: arthroscopic localization of an osteochondritis dissecans lesion of the knee. AB - We report on the arthroscopic treatment of a 12-year-old boy diagnosed with an osteochondral defect of the medial femoral condyle. He underwent arthroscopic fixation of the defect, and during the surgery, a blunt trocar was used to localize the lesion. The trocar created a transient dimpling effect on the cartilage overlying the osteochondral defect that resembled the surface of a golf ball. This "golf ball sign" then served as a visual guide during placement of a chondral dart. When present, it is believed that this sign can benefit arthroscopists by helping to improve intraoperative localization of an osteochondral defect. PMID- 25126501 TI - Arthroscopic Resection of Intra-Articular Osteochondromas of the Hip. AB - Proximal femur osteochondromas are relatively rare, particularly in the femoral neck. The choice of treatment poses difficulties to the surgeon. We report an unusual case of a patient with 2 osteochondromas in the femoral neck causing femoroacetabular impingement. Appropriate identification and precise resection of the lesions are important steps of the surgical procedure. We present our arthroscopic surgical technique to access the lesions and perform their resection. To our knowledge, this is the first report of hip arthroscopic resection of 2 osteochondromas with considerable dimensions causing femoroacetabular impingement. PMID- 25126502 TI - Arthroscopic hip labral repair: the iberian suture technique. AB - Arthroscopic hip labral repair has beneficial short-term outcomes; however, debate exists regarding ideal surgical labral repair technique. This technical note presents an arthroscopic repair technique that uses intrasubstance labral suture passage to restore the chondrolabral interface. This "Iberian suture technique" allows for an anatomic repair while posing minimal risk of damage to the labral and chondral tissues. PMID- 25126503 TI - Arthroscopic labral reconstruction of the hip using local capsular autograft. AB - Labral reconstruction is becoming an important treatment modality for hips with nonsalvageable labra. Nonsalvageable labra can be present in cases of intrasubstance damage, revision surgery after debridement, labral calcification, and hypoplasia. Previous methods of reconstruction have been performed in an open manner and arthroscopically using ligamentum teres, iliotibial band, and gracilis autograft. We present an alternate method of arthroscopic labral reconstruction using capsular autograft. The technique uses readily available capsular tissue during arthroscopy with no donor-site morbidity. This technique may be valuable in appropriately selected patients with labral deficiency. PMID- 25126504 TI - Recycling Suture Limbs from Knotless Suture Anchors for Arthroscopic Shoulder Stabilization. AB - Recurrent shoulder instability often leads to labral abnormality that requires surgical intervention that may require fixation with suture anchors. The proposed surgical technique allows the surgeon to achieve 2 points of fixation around the labrum and/or capsule with a single suture secured to the glenoid with a knotless anchor. Instead of cutting and discarding the residual suture limbs after anchor insertion, this technique uses the residual suture limbs of the knotless anchor for a second suture pass. This technique (1) creates a more cost- and time efficient surgical procedure than using multiple single-loaded anchors or double loaded anchors, (2) decreases the known risk of glenoid fracture from the stress riser at the implant tips of multi-anchor repairs by reducing the number of anchors required for stabilization, (3) decreases the surgical time compared with the use of double-loaded anchors through simpler suture management and less knot tying, (4) allows for the secure reapproximation of the labrum to the glenoid while offering a convenient option for capsulorrhaphy without the need to insert another anchor, and (5) yields more points of soft-tissue fixation with fewer anchors drilled into the glenoid. PMID- 25126505 TI - A new technique for patch augmentation of rotator cuff repairs. AB - Massive rotator cuff tears defying primary repair have been treated with debridement, arthroscopic subacromial decompression, partial repair, muscle tendon transfer, and joint prosthesis, among other techniques. However, the treatment results have not been satisfactory compared with those of small- to medium-sized rotator cuff tears; each procedure has its merits and demerits, and currently, there is no single established method. For massive rotator cuff tears defying primary repair, the arthroscopic patch graft procedure has been reported as an effective surgical procedure, and this procedure is chosen as the first line treatment in our department. In this procedure, suture anchors are generally used to fix the patch graft to the footprint on the side of the greater tuberosity. However, tendon-to-bone healing is frequently difficult to achieve, and bone-to-bone healing seems more advantageous for the repair of the rotator cuff attachment site. To improve the results of treatment, a new patch graft procedure was developed, in which the iliotibial ligament with bone was collected at Gerdy's tubercle and the bone was anchored to the footprint on the side of the greater tuberosity. With this procedure, excellent results were obtained, although only short-term results are available at present. The technique and its results so far are reported. PMID- 25126506 TI - Arthroscopic technique for the treatment of patellar chondral lesions with the patient in the supine position. AB - We describe an arthroscopic approach for the treatment of patellar chondral lesions with the patient in the supine position. This approach can be used to perform certain procedures such as matrix autologous chondrocyte implantation and autologous matrix-induced chondrogenesis. It is possible to perform these arthroscopic techniques working at an angle perpendicular to the patellar joint surface. First, with the patient in the supine position, arthroscopic longitudinal sectioning of the lateral patellar retinaculum is performed, and the patella is reverted with the help of a Codivilla forceps. It is then possible to place the chondral surface perpendicular to the floor, and it can be accessed directly through a lateral parapatellar portal. Short-term follow-up has shown the benignity of opening the patellar retinaculum. This procedure reduces morbidity compared with the traditional open surgery. PMID- 25126507 TI - Arthroscopic Treatment of Acute Tibial Avulsion Fracture of the Posterior Cruciate Ligament Using the TightRope Fixation Device. AB - Avulsion fracture of the posterior cruciate ligament from its tibial insertion is a rare condition. Early surgical treatment has been regarded as necessary, but the optimal surgical technique remains unclear. The purpose of this technical note is to present a novel all-inside arthroscopic reconstruction technique for bony tibial avulsion fractures of the posterior cruciate ligament using the TightRope device (Arthrex, Naples, FL). PMID- 25126508 TI - Endoscopic robotic decompression of the ulnar nerve at the elbow. AB - Ulnar nerve entrapment can be treated by a number of surgical techniques when necessary. Endoscopic techniques have recently been developed to access the ulnar nerve by use of a minimally invasive approach. However, these techniques have been considered difficult and, many times, dangerous procedures, reserved for experienced elbow arthroscopic surgeons only. We have developed a new endoscopic approach using the da Vinci robot (Intuitive Surgical, Sunnyvale, CA) that may be easier and safer. Standardization of the technique was previously developed in cadaveric models to achieve the required safety, reliability, and organization for this procedure, and the technique was then used in a live patient. In this patient the nerve entrapment symptoms remitted after the surgical procedure. The robotic surgical procedure presented a cosmetic advantage, as well as possibly reduced scar formation. This is the first note on this surgical procedure; the procedure needs to be tested and even evolved until a state-of-the-art standard is reached. PMID- 25126509 TI - Arthroscopic Identification of the Anterolateral Ligament of the Knee. AB - Intense interest has focused on the recent description of the anterolateral ligament of the knee. Advancing knowledge of its anatomy and function is leading to a realization of its importance in the rotatory control of the tibia in anterior cruciate ligament injuries. Reconstruction of this structure will increasingly become an important goal during anterior cruciate ligament reconstruction. However, preoperative assessment of this ligament is difficult. Clinical assessment of rotatory laxity has poor reproducibility, and it is difficult to define using current imaging techniques. This article is the first to describe a safe and reproducible arthroscopic technique to allow identification and examination of the anterolateral ligament of the knee. With the knee at 90 degrees of flexion, the arthroscope is introduced through the anterolateral portal to allow clear visualization of the lateral gutter. Under direct vision, an accessory portal is made over the inferior limit of the lateral gutter. A shaver is then introduced through this portal and used to debride this synovial recess and define the anterolateral ligament. This allows the surgeon to examine the integrity of the anterolateral ligament, in particular its femoral insertion. If required, this additional information can facilitate the performance of a more accurate and effective extra-articular reconstruction. PMID- 25126511 TI - Arthroscopic Treatment of Cartilage Lesions With Microfracture and BST-CarGel. AB - Bone marrow stimulation techniques for the treatment of articular cartilage defects such as microfracture so far have solely reproduced mechanically inferior fibrous cartilage tissue, which might result in unsatisfactory clinical results at midterm follow-up. A recent study has shown an improvement in repair tissue quality by enhancing microfracture with a chitosan-based biomaterial (BST-CarGel; Piramal, Laval, Quebec, Canada). BST-CarGel so far has only been applied by arthrotomy, which might lead to increased scar tissue formation and thus compromise recovery time and clinical outcome. We describe a surgical technique for an arthroscopic treatment of cartilage defects of the knee with microfracture in combination with BST-CarGel to benefit from improved repair tissue quality and to reduce arthrotomy-related morbidity. PMID- 25126510 TI - Reconstruction of the posterolateral corner of the knee with achilles tendon allograft. AB - Posterolateral corner injuries of the knee are relatively rare; however, they can result in significant long-term disability without appropriate treatment. They often occur in the setting of multiligament knee injuries, and as a result, diagnosis and management can be challenging. Severe injuries often require reconstruction, and both anatomic and nonanatomic techniques exist. We describe our preferred operative technique to reconstruct the fibular collateral ligament and posterolateral corner using a single Achilles tendon allograft. PMID- 25126512 TI - Arthroscopic bankart repair: accessory posterior portal with slotted cannula for lowest capsulolabral access. AB - We present a novel technique for safe establishment of the accessory posterior portal using a slotted cannula. Arthroscopic Bankart repair is a common procedure. A variety of arthroscopic techniques have been described in the literature, commonly using the posterior portal for visualization and the anterior portal with a working cannula. The accessory posterior portal enables elegant access to the lower part of the capsulolabral junction, a firmer grasp and mobilization of the tissue, quick and easy tool exchange using a slotted cannula, and clearer suture placement because of the flat, direct working angle. The skin incision is made small without the need for an arthroscopic cannula, and the portal location is in a relatively safe zone. The use of the accessory posterior portal along with a slotted cannula shortens the duration of the operative procedure and improves safety and performance. PMID- 25126513 TI - Hybrid Repair of Large Crescent Rotator Cuff Tears Using a Modified SpeedBridge and Double-Pulley Technique. AB - An ideal rotator cuff repair maximizes the tendon-bone interface and has adequate biomechanical strength that can withstand a high level of demand. Arthroscopic transosseous-equivalent rotator cuff repairs have become popular and have been shown to be superior to many other methods of fixation. We present an alternative method of repair for large crescent rotator cuff tears that combines 2 well-known methods of fixation: modified SpeedBridge (Arthrex, Naples, FL) and double-pulley techniques. These 2 repair constructs were combined to provide the greatest amount of compression across the footprint while also providing rigid fixation. Ultimately, this can provide an optimal environment for healing in otherwise significant injuries. PMID- 25126514 TI - Arthroscopic resection of fat pad lesions and infrapatellar contractures. AB - The infrapatellar fat pad (IFP), also known as Hoffa's fat pad, may be a common site of pain in the knee because of its susceptibility to injury and its vast innervation and vascular supply. Patients who have trauma to the IFP may undergo a process of hemorrhage, inflammation, and fibrosis that may become painful. Patients with Hoffa's disease in whom conservative treatment with medications, physical therapy, and injections has failed may receive significant pain relief and benefit from undergoing arthroscopic subtotal removal of the IFP. We describe a safe and effective way to perform this procedure allowing excellent visualization through the use of a superolateral viewing portal. PMID- 25126515 TI - Avoiding graft-tunnel length mismatch in anterior cruciate ligament reconstruction: the single-bone plug technique. AB - Anterior cruciate ligament reconstruction, using autogenous bone-patellar tendon bone (BTB) as a graft material, is commonly performed in the setting of anterior cruciate ligament insufficiency. Although bone-patellar tendon-bone autograft has an extensive track record, showing excellent clinical results, donor-site morbidity and graft-tunnel mismatch can still be problematic for a subset of patients. In the setting of a tendon graft that is too long, adequate interference screw fixation cannot be obtained, typically resulting in a tibial sided bone plug that achieves less than 15 to 20 mm of bone in the distal tibial tunnel. We present an easy and effective technique for avoiding the graft-tunnel mismatch problems that commonly occur in patients who have an excessively long patellar tendons. This technique involves a simple preoperative planning algorithm that ultimately results in a single tibial-sided plug harvest. Bony interference fixation is then obtained on the femoral side and soft-tissue fixation on the tibial side. This technique allows for satisfactory graft fixation while avoiding the donor-site morbidity associated with patellar bone plug harvest. PMID- 25126517 TI - Chocolate consumption and prevalence of metabolic syndrome in the NHLBI Family Heart Study. AB - BACKGROUND & AIMS: Previous studies have suggested that cocoa products, which are rich sources of flavonoids, may lower blood pressure, serum cholesterol, fasting blood glucose and improve endothelial function. However, it is unclear whether consumption of cocoa products including chocolate influences the risk of metabolic syndrome (MetS). In a cross-sectional design, we sought to examine the association between chocolate consumption and the prevalence of MetS. METHODS: We studied 4098 participants from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study aged 25-93 years. Chocolate consumption was assessed using a semi-quantitative food-frequency questionnaire. MetS was defined using the NCEP III criteria. Generalized estimating equations were used to estimate prevalence odds ratios of MetS according to frequency of chocolate intake. RESULTS: Of the 4098 participants (mean age 51.7 y) included in the analyses, 2206 (53.8%) were female. The prevalence of metabolic syndrome in our population was 30.2%. Compared with those who did not consume any chocolate, multivariate adjusted odds ratios (95% CI) for MetS were 1.26 (0.94, 1.69), 1.15 (0.85, 1.55), and 0.99 (0.66, 1.51) among women who reported chocolate consumption of 1-3 times/ month, 1-4 times/week, and 5+ times/week, respectively. Corresponding values for men were: 1.13 (0.82, 1.57), 1.02 (0.74, 1.39), and 1.21 (0.79, 1.85). CONCLUSION: These data do not support an association between chocolate intake and the prevalence of MetS in US adult men and women. PMID- 25126519 TI - Genome-wide DNA binding pattern of the homeodomain transcription factor Sine oculis (So) in the developing eye of Drosophila melanogaster. AB - The eye of the fruit fly Drosophila melanogaster provides a highly tractable genetic model system for the study of animal development, and many genes that regulate Drosophila eye formation have homologs implicated in human development and disease. Among these is the homeobox gene sine oculis (so), which encodes a homeodomain transcription factor (TF) that is both necessary for eye development and sufficient to reprogram a subset of cells outside the normal eye field toward an eye fate. We have performed a genome-wide analysis of So binding to DNA prepared from developing Drosophila eye tissue in order to identify candidate direct targets of So-mediated transcriptional regulation, as described in our recent article [1]. The data are available from NCBI Gene Expression Omnibus (GEO) with the accession number GSE52943. Here we describe the methods, data analysis, and quality control of our So ChIP-seq dataset. PMID- 25126520 TI - Gene expression signatures affected by ethanol and/or nicotine in normal human normal oral keratinocytes (NHOKs). AB - It has been reported that nicotine/alcohol alter epigenetic control and lead to abrogated DNA methylation and histone modifications, which could subsequently perturb transcriptional regulation critically important in cellular transformation. The aim of this study is to determine the molecular mechanisms of nicotine/alcohol-induced epigenetic alterations and their mechanistic roles in transcriptional regulation in human adult stem cells. We hypothesized that nicotine/alcohol induces deregulation of epigenetic machinery and leads to epigenetic alterations, which subsequently affect transcriptional regulation in oral epithelial stem cells. As an initiating step we have profiled transcriptomic alterations induced by combinatory administration of EtOH and nicotine in primary normal human oral keratinocytes. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO) under GSE57634. Our data provide comprehensive transcriptomic map describing molecular changes induced by EtOH and nicotine on normal human oral keratinocytes. PMID- 25126522 TI - Lipid nanoceuticals: Current status and future perspective. PMID- 25126518 TI - Aging-dependent changes in rat heart mitochondrial glutaredoxins--Implications for redox regulation. AB - Clinical and animal studies have documented that hearts of the elderly are more susceptible to ischemia/reperfusion damage compared to young adults. Recently we found that aging-dependent increase in susceptibility of cardiomyocytes to apoptosis was attributable to decrease in cytosolic glutaredoxin 1 (Grx1) and concomitant decrease in NF-kappaB-mediated expression of anti-apoptotic proteins. Besides primary localization in the cytosol, Grx1 also exists in the mitochondrial intermembrane space (IMS). In contrast, Grx2 is confined to the mitochondrial matrix. Here we report that Grx1 is decreased by 50-60% in the IMS, but Grx2 is increased by 1.4-2.6 fold in the matrix of heart mitochondria from elderly rats. Determination of in situ activities of the Grx isozymes from both subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria revealed that Grx1 was fully active in the IMS. However, Grx2 was mostly in an inactive form in the matrix, consistent with reversible sequestration of the active-site cysteines of two Grx2 molecules in complex with an iron-sulfur cluster. Our quantitative evaluations of the active/inactive ratio for Grx2 suggest that levels of dimeric Grx2 complex with iron-sulfur clusters are increased in SSM and IFM in the hearts of elderly rats. We found that the inactive Grx2 can be fully reactivated by sodium dithionite or exogenous superoxide production mediated by xanthine oxidase. However, treatment with rotenone, which generates intramitochondrial superoxide through inhibition of mitochondrial respiratory chain Complex I, did not lead to Grx2 activation. These findings suggest that insufficient ROS accumulates in the vicinity of dimeric Grx2 to activate it in situ. PMID- 25126521 TI - The RPTEC/TERT1 cell line models key renal cell responses to the environmental toxicants, benzo[a]pyrene and cadmium. AB - We have characterized initial canonical responses to two environmental toxicants, cadmium (Cd) and benzo[a]pyrene (B[a]P), in a novel in vitro model derived from renal proximal tubule epithelial cells (RPTEC) of a healthy human donor. The RPTEC/TERT1 cell line has been immortalized using the human telomerase reverse transcriptase (hTERT) subunit only and does not exhibit chromosomal abnormalities. RPTEC/TERT1 cells were exposed to single-compound and binary mixtures of Cd and B[a]P, known or suspected renal toxicants respectively. Cells exhibited cytotoxicity to concentrations of B[a]P and Cd as low as 1 nm and 3 MUM, respectively. RPTEC/TERT1 cells exhibited compound-specific gene expression responses when exposed to 0.01-1 MUM B[a]P and 0.1-10 MUM Cd. A significant increase in the expression of genes coding for B[a]P metabolizing enzymes (CYP1A1, CYP1B1) occurred in a dose and time dependent manner at 3, 6, and 24 h post exposure. Likewise, a significant increase in the heavy metal responsive gene MT2A was observed following exposure to Cd. The EROD activity assay confirmed significant increases in CYP1(A/B) activity after 24 h of exposure to B[a]P which was not affected by the presence of Cd. Co-exposure to low concentrations of Cd and B[a]P were consistent with changes in gene expression as seen with single-compound exposures. These experiments are the first to provide information regarding toxicological responses in the RPTEC/TERT1 cell line that model those of the target tissue. We conclude that these cells can provide a useful tool for future toxicological studies. PMID- 25126523 TI - Pharmacoeconomics guidelines: The need of hour for India. AB - Although the government pays for approximately 20% of drugs used in India, private out-of-pocket expenditure in India on health-care is one of the highest in the world. Preparing pharmacoeconomics guidelines will be an important step in order to establish Health Technology Assessment (HTA) in India. Areas in which HTA could be applied in the Indian context include, drug pricing, development of clinical practice guidelines and prioritizing interventions that represent the greatest value within a limited budget. All this calls for action, both by government and civil-society organizations, to make access to essential medicines a priority. PMID- 25126524 TI - Formulation and evaluation of stimuli-sensitive hydrogels of timolol maleate and brimonidine tartrate for the treatment of glaucoma. AB - BACKGROUND: Stimuli-sensitive hydrogels are hydrophilic, three-dimensional, polymeric network structure capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature, and ionic change. Owing to the drawback of conventional therapy for ocular delivery, and to provide additive effect on intraocular pressure (IOP) reduction, stimuli sensitive hydrogel membranes containing a combination of timolol maleate and brimonidine tartrate were formulated for the treatment of glaucoma. MATERIALS AND METHODS: Stimuli-sensitive hydrogel were formulated by timolol maleate and brimonidine tartrate. Poly acrylic acid (carbopol C 934p) is used as a gelling agent, hydroxylpropyl methylcellulose as viscolizer, sodium chloride as tonicity agent. Bezalkonium chloride as preservative. White rabbits of both sexes, weighing between 2 and 3 kg were used for the study. Stirring of ingredients in pH 4 phosphate buffers at high speed was carried out. RESULT: Viscosity of the prepared hydrogels lies in the optimum range that is, 25-55 cps. Infrared spectroscopy studies show that there is no interaction between the drug and polymer. Drug released up to 90% at the end of 8 h. The hydrogel membranes were found to be sterile, nonirritant to the eye. Marketed formulation showed a decrease in IOP up to 14 mmHg at the end of 5 h and then elimination of drug, F2 and F6 maintain the sustained effect up to 12 h. CONCLUSION: Stimuli-sensitive hydrogels was successfully formulated and evaluated for rheological studies, drug release studies, drug interaction studies, sterility studies, ocular irritation studies, and in vivo studies. IOP lowering activity of the combination of timolol maleate and brimonidine tartrate in stimuli-sensitive hydrogel was better when compared with alone medication, which shows the additive effect of combination medication. PMID- 25126525 TI - Nanovesicles for transdermal delivery of felodipine: Development, characterization, and pharmacokinetics. AB - AIM: The research traces development of nanovesicles to attain enhanced transdermal delivery of felodipine and also investigates parameters for optimization of variable membrane compositions containing soya- and egg lecithin and edge activator. MATERIALS AND METHODS: Rotary evaporation sonication method was employed to obtain tranfersomal formulation that was characterized for vesicle shape and size, polydispersity index (PDI), zeta potential, entrapment and loading efficiency, deformability index and in vitro skin permeation. RESULTS: Spherical nanovesicles of 75.71 +/- 5.4 nm with PDI 0.228 and zeta potential of -49.8 were adjudged as the best formulation (MF8). MF8 displayed maximum entrapment and loading efficiency with a high deformability index of 119.68. In vitro permeation across rat skin by MF8 reported 256% enhancement in permeation (flux = 23.72 +/- 0.64) when compared with transdermal control formulation and followed zero order kinetics (Case-II). Pharmacokinetic studies revealed that transdermal administration, in contrast to oral delivery provided relatively constant, sustained blood concentration with minimal plasma fluctuation, rapid and prolonged peak time. The relative bioavailability of felodipine was found 358.42% versus oral administration that was well supported by the outcomes of confocal laser scanning microscopic studies that suggested rapid permeation of drugs to across dermal layers. CONCLUSION: The results conclude that composition variation and method of preparation elicited significant effect on the vesicle characteristic and proved the transcendency of felodipine loaded transfersomes. PMID- 25126526 TI - Preparation and characterization of amorphous ezetimibe nanosuspensions intended for enhancement of oral bioavailability. AB - OBJECTIVE: The objective of this study was to prepare and investigate better and stable amorphous ezetimibe nanosuspensions for oral bioavailability enhancement. MATERIALS AND METHODS: Nanosuspensions of ezetimibe were prepared by solvent antisolvent precipitation technique using the surfactant, Tween 80 as stabilizer. The nanosuspension preparation was optimized for particle size by investigating two factors that is, solvent:antisolvent ratio and surfactant concentration, at three levels. The formulations were characterized for particle size, surface morphology, crystallinity, zeta potential, saturation solubility, in vitro drug release and in vivo drug absorption. RESULTS: The nanosuspensions of ezetimibe were successfully prepared using solvent-antisolvent precipitation. The two factors solvent:antisolvent ratio and surfactant concentration influenced the particle size of the nanosuspensions prepared. Nanosuspensions were smooth and spherical. The X-ray powdered diffraction and differential scanning calorimetry results indicated that the antisolvent-solvent method led to the amorphization of ezetimibe. Under storage, the amorphous ezetimibe nanosuspensions demonstrated significant physical stability. Ezetimibe nanosuspensions increased the saturation solubility to an extent of 4-times. Ezetimibe nanosuspensions completely dissolved in the dissolution medium within 1 h, while pure drug was dissolved up to 42% during same time. The Cmax with ezetimibe nanosuspension was approximately 3-fold higher when compared with that of ezetimibe conventional suspensions administered orally. CONCLUSIONS: Stable amorphous ezetimibe nanosuspensions were successfully prepared and these nanosuspensions demonstrated dramatic improvement in oral bioavailability of the active. PMID- 25126527 TI - Comparison of effectiveness of curcumin with triamcinolone acetonide in the gel form in treatment of minor recurrent aphthous stomatitis: A randomized clinical trial. AB - INTRODUCTION: Recurrent aphthous stomatitis (RAS) is an unfortunately most common disease occurring in oral cavity. Although the lesion is usually self-limited, its painful presentation, high frequency of occurrence, and multifactorial etiology leads to significant morbidity. So, an efficient therapeutic strategy is needed to provide relief to the patients. AIM: To assess and compare the efficacy of Curcumin with Triamcinolone acetonide in the gel form in treatment of minor RAS. MATERIALS AND METHODS: As a randomized clinical trial, 60 patients of either sex with clinically diagnosed RAS were randomly divided into 2 groups-Curcumin gel group (Group I) and Triamcinolone Acetonide gel group (Group II). Patients in either group were asked to apply the gel three times a day on each ulcer. Assessment of efficacy of gel was done on the basis of time required for regression in pain, size, and number of the ulcers. RESULTS: The results showed significant difference in size, pain, number, and duration of ulcers in Group I and Group II within a period of 7 days. However, no significant difference was noted in both the groups in the treatment of RAS. To evaluate the efficacy, Mann Whitney U test was used and statistical analysis was done using Statistical Package for the Social Sciences (SPSS) 19 software. CONCLUSION: Curcumin has strong antioxidant, with anti-inflammatory, immunomodulatory and analgesic properties, which according to the results obtained from the present study, can be used as an effective alternative to steroids in treatment of RAS. PMID- 25126529 TI - Nanotechnology: The vision of 2025. PMID- 25126528 TI - Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug-Efavirenz. AB - PURPOSE OF THE STUDY: The antiretroviral therapy (ART) has dramatically improved human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treatment, prevention and also has been found to increase the lifespan of HIV/AIDS patients by providing durable control of the HIV replication in patients. Efavirenz is a non-nucleoside reverse transcriptase inhibitor of HIV-1. The purpose of this study is to formulate efavirenz-loaded bovine serum albumin nanoparticles to improve efavirenz delivery into various organs. MATERIALS AND METHODS: Nanoparticles were prepared by desolvation technique and coated with polysorbate 80. Ethanol, glutaraldehyde, and mannitol were used as desolvating, cross linking agent, and cryoprotectant, respectively. Drug to polymer ratio was chosen at five levels from 1:2, 1:3, 1:4, 1:5, and 1:6 (by weight). The formulated nanoparticles were characterized for Fourier Transform Infrared (FT IR) spectroscopy, differential scanning calorimetry (DSC) studies, entrapment efficiency, particle size, surface charge, surface morphology, in vitro drug release, release kinetics, stability studies, and biodistribution studies. RESULTS AND MAJOR CONCLUSION: The particle size of the prepared formulations was found below 250nm with narrow size distribution, spherical in shape and showed good entrapment efficiency (45.62-72.49%). The in vitro drug release indicated biphasic release and its data were fitted to release kinetics models and release pattern was Fickian diffusion controlled release profile. The prepared nanoparticles increased efavirenz delivery into various organs by several fold in comparison with the free drug. PMID- 25126530 TI - Role of pharmacists in retailing of drugs. PMID- 25126531 TI - Method development and validation of liquid chromatography-tandem/mass spectrometry for aldosterone in human plasma: Application to drug interaction study of atorvastatin and olmesartan combination. AB - In the present investigation, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for the quantification of aldosterone (ALD) a hormone responsible for blood pressure in human plasma. The developed method was validated and extended for application on human subjects to study drug interaction of atorvastatin (ATSV) and olmesartan (OLM) on levels of ALD. The ALD in plasma was extracted by liquid-liquid extraction with 5 mL dichloromethane/ethyl ether (60/40% v/v). The chromatographic separation of ALD was carried on Xterra, RP-Column C18 (150 mm* 4.6 mm * 3.5 MUm) at 30 degrees C followed by four-step gradient program composed of methanol and water. Step 1 started with 35% methanol for first 1 min and changed linearly to 90% in next 1.5 min in Step 2. Step 3 lasted for next 2 min with 90% methanol. The method finally concluded with Step 4 to achieve initial concentration of methanol that is, 35% thus contributing the total method run time of 17.5 min. The flow rate was 0.25 mL/min throughout the process. The developed method was validated for specificity, accuracy, precision, stability, linearity, sensitivity, and recovery. The method was linear and found to be acceptable over the range of 50 800 ng/mL. The method was successfully applied for the drug interaction study of ATSV + OLM in combination against OLM treatment on blood pressure by quantifying changes in levels of ALD in hypertensive patients. The study revealed levels of ALD were significantly higher in ATSV + OLM treatment condition when compared to OLM as single treated condition. This reflects the reason of low effectiveness of ATSV + OLM in combination instead of synergistic activity. PMID- 25126532 TI - Multi criteria decision making to select the best method for the preparation of solid lipid nanoparticles of rasagiline mesylate using analytic hierarchy process. AB - The objective of this study was to select best method for the development of rasagiline mesylate (RM) loaded nanoscale solid lipid particles using analytic hierarchy process (AHP). Improper method selection may lead to waste of time, loss of material and financial resources. One of the possibilities to overcome these difficulties, AHP was employed to find the suitable method. In the AHP, a decision of hierarchy was constructed with a goal, criteria, sub-criteria, and alternatives. After constructing the AHP, the expert choice software was used to compute the overall priority of criteria, sub-criteria and alternatives. The best alternative selected was based on the highest priority. Nanoscale solid lipid particles of RM was formulated by the selected microemulsion method (M4) and it shows the particle size, polydispersity index and zeta potential were within acceptable limits. Drug content and entrapment efficiency of the RM-solid lipid nanoparticles were 97.26% and 86.57%, respectively. This study concludes that the AHP was viable and effective tool for selecting a most suitable method for the fabrication of RM loaded nanoscale solid lipid particles. PMID- 25126533 TI - Comparative antidiarrheal and antiulcer effect of the aqueous and ethanolic stem bark extracts of Tinospora cordifolia in rats. AB - Tinospora cordifolia is indigenous to the tropical areas of India, Myanmar and Sri Lanka. The use of plant as remedy for diarrhea and ulcer is well-documented in Ayurvedic system of medicine. However, pharmacological evidence does not exist to substantiate its therapeutic efficacy for the same. The aim was to investigate the antidiarrheal and antiulcer activity of ethanolic and aqueous extracts of T. cordifolia in rats. The antidiarrheal activity of T. cordifolia extracts was evaluated by castor oil and magnesium sulfate-induced diarrhea using parameters such as onset of diarrhea, number of wet stools, total number of stool and weight of total number of stools. The antiulcer activity of extracts was investigated using ethanol and pylorus ligation-induced ulcer. Furthermore, tissue antioxidant parameters such as reduced glutathione, catalase activity and lipid peroxidation level were also investigated. Tinospora cordifolia extracts were more efficacious in reducing number of total stools in both the models of diarrhea and showed a dose-dependent antidiarrheal effect. The antiulcer activity of the extracts was confirmed by a reduction in ulcer index along with the decrease in gastric volume, total acidity, and an increase in pH of gastric content in both the models. The obtained results have established a pharmacological evidence for the folkloric use of the T. cordifolia as antidiarrhoeal and antiulcer agent. PMID- 25126534 TI - Evaluation of analgesic activity of perindopril in albino mice. AB - The aim was to evaluate the analgesic activity of perindopril in chemical, thermal and mechanical pain on Swiss albino mice. A total of 54 albino mice (Swiss strain) weighing 25-30 g were allocated to each experimental model and in each model there were three groups. The control group received normal saline (25 ml/kg) per orally, standard group received pentazocine (10 mg/kg) intra peritoneal and test groups received perindopril (1 mg/kg) per orally. Perindopril and normal saline was administered 2 h before, whereas the pentazocine was administered 15 min prior to Eddy's hot plate, writhing and tail clip methods. The decrease in number of writhes, the delay in reaction time in tail clip and Eddy's hot plate method denoted the analgesic activity. Perindopril decreased the number of writhes, delayed the reaction time in tail clip and Eddy's hot plate method considerably when compared with control (normal saline), but less when compared with standard (pentazocine). Perindopril exhibits analgesic activity in thermal, chemical, and mechanical pain models in albino mice. PMID- 25126535 TI - Pharmacodynamic interaction of green tea extract with hydrochlorothiazide against ischemia-reperfusion injury-induced myocardial infarction. AB - Globally, the rate of development of myocardial diseases and hypertension is very common, which is responsible for incremental morbidity and mortality statistics. Treatment of ischemic hypertensive patients with diuretics such as hydrochlorothiazide (HCTZ) can precipitate myocardial infarction due to hypokalemia. This study was undertaken to evaluate the pharmacodynamic interaction of green tea extract (GTE) with HCTZ against ischemia-reperfusion induced myocardial toxicity. Wistar albino rats of either sex were taken and pretreated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of GTE for 30 days. Standard, high and low dose of interactive groups received HCTZ (10 mg/kg, p.o.) for last 7 days. Ischemia-reperfusion injury was induced by modified Lagendorff apparatus, and the effect of different treatments was evaluated by percentage recovery in terms of heart rate and developed tension, serum biomarkers, and heart tissue antioxidant levels. Prophylactic treatment groups, such as high and low dose of GTE and their interactive groups with HCTZ, exhibited significant percentage recovery in terms of heart rate and developed tension. Apart from that, significant increase in superoxide dismutase and catalase, decrease in thiobarbituric acid reactive species in heart tissue, as well as significant decrease in serum lactate dehydrogenase, creatinine phosphokinase-MB and N-acetylcysteine levels have also been documented. The present findings clearly suggest that GTE dose-dependently reduces myocardial toxicity due to ischemia, and combination with HCTZ can reduce the associated side-effects and exhibits myocardial protection. PMID- 25126536 TI - Role of different biodegradable polymers on the permeability of ciprofloxacin. AB - Since permeability across biological membranes is a key factor in the absorption and distribution of drugs, drug permeation characteristics of three oral suspensions of ciprofloxacin were designed and compared. The three suspensions of ciprofloxacin were prepared by taking biodegradable polymers such as carbopol 934, carbopol 940, and hydroxypropyl methylcellulose (HPMC). The permeability study was performed by using a Franz diffusion cell through both synthetic cellulose acetate membrane and excised goat gastrointestinal membranes in acidic as well as alkaline pH. To know the permeability of drug from control/formulations through different membranes in acidic/alkaline pH, cumulative percentage drug permeation, apparent permeability (Papp), flux, and enhancement ratio (ER) were calculated. Considering Papp and flux values of all formulations, it is evident that formulation containing HPMC was the most beneficial for improving permeation and diffusivity of ciprofloxacin even after 16 h. Hence, this preparation may be considered as the most suitable formulation to obtain prolonged release action of the drug. The ER values of all formulations, through excised goat intestinal mucosal membrane in alkaline pH, were higher than those formulations through goat stomach mucosal membrane in acidic pH. Enhancement ratio values of those formulations indicate that the permeability of the drug was more enhanced by the polymers in the intestinal part, leading to more bioavailability and prolonged action in that portion of the gastrointestinal tract. It may also be concluded from our results that HPMC containing formulation was the best suspension, which may show effective controlled release action. Even carbopol containing formulations might also produce controlled release action. PMID- 25126537 TI - A simple reversed phase high-performance liquid chromatography (RP-HPLC) method for determination of curcumin in aqueous humor of rabbit. AB - This article describes a simple and rapid method for determination of curcumin (diferuloylmethane) in aqueous humor of rabbit using high-performance liquid chromatography (HPLC). Analysis was performed using a C-18 column (250 * 4.6 mm, 5 MU luna) by isocratic elution with a mobile phase containing 25 mM potassium dihydrogen orthophosphate (pH 3.5): Acetonitrile (40:60) and detection at 424 nm using a photodiode array (PDA) detector for curcumin. The regression data for curcumin showed a good linear relationship with r(2)> 0.998 over the concentration range of 0.1-10 MUg ml(-1). Relative standard deviations (RSD) for the intraday and interday coefficient of variations for the assay were less than 5.0 and 8.5, respectively. The recovery of the method was between 79.8-83.6%. The quantification limit of the method for curcumin was 0.01 MUg ml(-1). This method has good accuracy, precision, and quantitation limit. It is also concluded that the method is useful for measuring very low curcumin concentrations in aqueous humor. PMID- 25126538 TI - Collaborative Care in NSCLC; the Role of Early Palliative Care. AB - The management of non-small cell lung cancer (NSCLC) has evolved into a multidisciplinary team approach that traditionally has involved medical oncology, radiation oncology, and thoracic surgery. However, in the era of personalized medicine the importance of molecular diagnostics requires adequate tissue for histologic subtyping and molecular testing and thus requires the engagement of other subspecialties such as pathology, respirology, and interventional radiology. Unfortunately in 2014, the majority of patients presenting with NSCLC will succumb to their disease and the early integration of palliative care into the treatment strategy will improve the quality of life and end-of-life care of our patients and may in fact improve their overall survival. PMID- 25126541 TI - Anima: modular workflow system for comprehensive image data analysis. AB - Modern microscopes produce vast amounts of image data, and computational methods are needed to analyze and interpret these data. Furthermore, a single image analysis project may require tens or hundreds of analysis steps starting from data import and pre-processing to segmentation and statistical analysis; and ending with visualization and reporting. To manage such large-scale image data analysis projects, we present here a modular workflow system called Anima. Anima is designed for comprehensive and efficient image data analysis development, and it contains several features that are crucial in high-throughput image data analysis: programing language independence, batch processing, easily customized data processing, interoperability with other software via application programing interfaces, and advanced multivariate statistical analysis. The utility of Anima is shown with two case studies focusing on testing different algorithms developed in different imaging platforms and an automated prediction of alive/dead C. elegans worms by integrating several analysis environments. Anima is a fully open source and available with documentation at www.anduril.org/anima. PMID- 25126539 TI - Hepatic radioembolization as a bridge to liver surgery. AB - Treatment of oncologic disease has improved significantly in the last decades and in the future a vast majority of cancer types will continue to increase worldwide. As a result, many patients are confronted with primary liver cancers or metastatic liver disease. Surgery in liver malignancies has steeply improved and curative resections are applicable in wider settings, leading to a prolonged survival. Simultaneously, radiofrequency ablation (RFA) and liver transplantation (LTx) have been applied more commonly in oncologic settings with improving results. To minimize adverse events in treatments of liver malignancies, locoregional minimal invasive treatments have made their appearance in this field, in which radioembolization (RE) has shown promising results in recent years with few adverse events and high response rates. We discuss several other applications of RE for oncologic patients, other than its use in the palliative setting, whether or not combined with other treatments. This review is focused on the role of RE in acquiring patient eligibility for radical treatments, like surgery, RFA, and LTx. Inducing significant tumor reduction can downstage patients for resection or, through attaining stable disease, patients can stay on the LTx waiting list. Hereby, RE could make a difference between curative of palliative intent in oncologic patient management. Prior to surgery, the future remnant liver volume might be inadequate in some patients. In these patients, forming an adequate liver reserve through RE leads to prolonged survival without risking post-operative liver failure and minimizing tumor progression while inducing hypertrophy. In order to optimize results, developments in procedures surrounding RE are equally important. Predicting the remaining liver function after radical treatment and finding the right balance between maximum tumor irradiation and minimizing the chance of inducing radiation-related complications are still challenges. PMID- 25126540 TI - Genetically modeled mice with mutations in mitochondrial metabolic enzymes for the study of cancer. AB - Mitochondrial dysfunction has long been implicated in progression of cancer. As a paradigm, the "Warburg effect," which by means of a switch toward anaerobic metabolism enables cancer cells to proliferate in oxygen limiting conditions, is well established. Besides this metabolic transformation of tumors, it has been discovered that mutations in genes encoding mitochondrial proteins are the etiological factors in different types of cancer. This confers to mitochondrial dysfunction a causative role, rather than resultant, in tumor genesis beyond its role in tumor progression and development. Mitochondrial proteins encoded by tumor-suppressor genes are part of the succinate-dehydrogenase, the fumarate hydratase, and the mitochondrial isocitrate-dehydrogenase enzymes, all of them participating in the Krebs cycle. The spectrum of tumors associated with mutations in these genes is becoming larger and varies between each enzyme. Several mechanisms of tumorigenesis have been proposed for the different enzymatic defects, most of them based on studies using cellular and animal models. Regarding the molecular pathways implicated in the oncogenic transformation, one of the first accepted theories was based on the constitutive expression of the hypoxia-inducible factor 1alpha (Hif1alpha) at normal oxygen tension, a theory referred to as "pseudo-hypoxic drive." This mechanism has been linked to the three types of mutations, thus suggesting a central role in cancer. However, other alternative molecular processes, such as oxidative stress or altered chromatin remodeling, have been also proposed to play an onco-pathogenic role. In the recent years, the role of oncometabolites, a new concept emerged from biochemical studies upon these tumors, has acquired relevance as responsible for tumor formation. Nevertheless, the actual contribution of each of these mechanisms has not been definitively established. In this review, we summarize the results obtained from mouse strains genetically modified in the three different enzymes. PMID- 25126542 TI - The effect of citrus peel extracts on cytokines levels and T regulatory cells in acute liver injury. AB - BACKGROUND: T cell-mediated immune responses contribute to the hepatocellular injury during autoimmune hepatitis, viral infection, and hepatotoxins. Pharmacological compounds regulating immune responses are suitable candidates for prevention/treatment of this pathology. Therefore, the main aim of this study was to define the effects of antioxidant, anti-inflammatory mixture of citrus peel extract (CPE) on the immune-mediated liver injury. METHODS: The influence of CPE on liver injury was determined by the activity of transaminases in plasma and the histological changes. Anti-inflammatory and antioxidant effects were studied by measuring frequency of T regulatory cells (Tregs), cytokines (TNF-alpha, IL-10, and IFN-gamma), and nitric oxide levels. RESULTS: The CPE application notably prevents development of liver injury through decreasing levels of both cytokines (TNF-alpha, INF) and regulatory T cells and increasing levels of IL-10. CPE injection also diminished the serum NO, which in turn resulted in evident reduction of the liver damage. CONCLUSION: Our findings represent the primary preclinical data indicating that the CPE in vivo could ameliorate Con A induced hepatitis. The low dose of CPE most likely can be used for the treatment of the T cell-mediated liver injury as in autoimmune hepatitis, alcoholic hepatitis, and chronic viral hepatitis. PMID- 25126545 TI - Visualization of polypropylene and polyvinylidene fluoride slings in perineal ultrasound and correlation with clinical outcome. AB - INTRODUCTION AND HYPOTHESIS: Complications and malfunctioning after TOT can occur due to several factors, such as the material of the sling. The aim of the present study is to evaluate morphology and functionality of two types of slings (PVDF; polypropylene) in vivo using perineal ultrasound (PUS). MATERIALS: In n = 47 women with TOT four criteria for PUS were taken and checked for possible differences: vertical stability of the sling position during Valsalva manoeuvre and contraction; distance "sling to urethra"; width of the sling and condition of the selvedges. RESULTS: We observed an increased vertical displacement of the PP slings, a significantly smaller variance to the extent of the displacement in PVDF-slings (P < 0.01), a significantly larger distance between sling and urethra (P < 0.001) in PVDF-slings, and a significantly smaller width of the PP-slings (P < 0.0001). CONCLUSION: Significant differences were found between the slings according to the four criteria. There was no difference established between the slings in the improvement of continence and no significant influence of the parameters was found for the resulting state of continence. In future studies, PUS may help to link differences in the morphology and functionality of in vivo slings to their material properties. PMID- 25126544 TI - Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using Box-Behnken design: in vitro and in vivo evaluation. AB - The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles (Lzp-PLGA-NPs) by investigating the effect of process variables on the response using Box-Behnken design. Effect of four independent factors, that is, polymer, surfactant, drug, and aqueous/organic ratio, was studied on two dependent responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were successfully developed by nanoprecipitation method using PLGA as polymer, poloxamer as surfactant and acetone as organic phase. NPs were characterized for particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction using FTIR. The developed NPs showed nearly spherical shape with z-average 167 318 d.nm, PDI below 0.441, and -18.4 mV zeta potential with maximum % drug entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas model and showed initial burst release of 21.7 +/- 1.3% with prolonged drug release of 69.5 +/- 0.8% from optimized NPs up to 24 h. In vitro drug release data was found in agreement with ex vivo permeation data through sheep nasal mucosa. In vitro cell viability study on Vero cell line confirmed the safety of optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to establish nose-to-brain pathway. PMID- 25126543 TI - Ligation strategies for targeting liposomal nanocarriers. AB - Liposomes have been exploited for pharmaceutical purposes, including diagnostic imaging and drug and gene delivery. The versatility of liposomes as drug carriers has been demonstrated by a variety of clinically approved formulations. Since liposomes were first reported, research of liposomal formulations has progressed to produce improved delivery systems. One example of this progress is stealth liposomes, so called because they are equipped with a PEGylated coating of the liposome bilayer, leading to prolonged blood circulation and improved biodistribution of the liposomal carrier. A growing research area focuses on the preparation of liposomes with the ability of targeting specific tissues. Several strategies to prepare liposomes with active targeting ligands have been developed over the last decades. Herein, several strategies for the functionalization of liposomes are concisely summarized, with emphasis on recently developed technologies for the covalent conjugation of targeting ligands to liposomes. PMID- 25126547 TI - Biotemplated synthesis of anatase titanium dioxide nanoparticles via lignocellulosic waste material. AB - Anatase titanium dioxide nanoparticles (TiO2-NPs) were synthesized by sol-gel method using rice straw as a soft biotemplate. Rice straw, as a lignocellulosic waste material, is a biomass feedstock which is globally produced in high rate and could be utilized in an innovative approach to manufacture a value-added product. Rice straw as a reliable biotemplate has been used in the sol-gel method to synthesize ultrasmall sizes of TiO2-NPs with high potential application in photocatalysis. The physicochemical properties of titanium dioxide nanoparticles were investigated by a number of techniques such as X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, thermogravimetric analysis (TGA), ultraviolet visible spectra (UV-Vis), and surface area and pore size analysis. All results consensually confirmed that particle sizes of synthesized titanium dioxide were template-dependent, representing decrease in the nanoparticles sizes with increase of biotemplate concentration. Titanium dioxide nanoparticles as small as 13.0 +/- 3.3 nm were obtained under our experimental conditions. Additionally, surface area and porosity of synthesized TiO2-NPs have been enhanced by increasing rice straw amount which results in surface modification of nanoparticles and potential application in photocatalysis. PMID- 25126546 TI - Genome-wide uncovering of STAT3-mediated miRNA expression profiles in colorectal cancer cell lines. AB - Colorectal cancer (CRC) is one of the most common malignancies resulting in high mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which is frequently activated and aberrantly expressed in CRC. MicroRNAs (miRNAs) are a class of small noncoding RNAs which play important roles in many cancers. However, little is known about the global miRNA profiles mediated by STAT3 in CRC cells. In the present study, we applied RNA interference to inhibit STAT3 expression and profiled the miRNA expression levels regulated by STAT3 in CRC cell lines with deep sequencing. We found that 26 and 21 known miRNAs were significantly overexpressed and downexpressed, respectively, in the STAT3-knockdown CRC cell line SW480 (SW480/STAT3-siRNA) compared to SW480 transfected with scrambled siRNAs (SW480/siRNA-control). The miRNA expression profiling was then validated by quantitative real-time PCR for selected known miRNAs. We further predicted the putative target genes for the dysregulated miRNAs and carried out functional annotation including GO enrichment and KEGG pathway analysis for selected miRNA targets. This study directly depicts STAT3-mediated miRNA profiles in CRC cells, which provides a possible way to discover biomarkers for CRC therapy. PMID- 25126548 TI - Assessment of waveform similarity in clinical gait data: the linear fit method. AB - The assessment of waveform similarity is a crucial issue in gait analysis for the comparison of kinematic or kinetic patterns with reference data. A typical scenario is in fact the comparison of a patient's gait pattern with a relevant physiological pattern. This study aims to propose and validate a simple method for the assessment of waveform similarity in terms of shape, amplitude, and offset. The method relies on the interpretation of these three parameters, obtained through a linear fit applied to the two data sets under comparison plotted one against the other after time normalization. The validity of this linear fit method was tested in terms of appropriateness (comparing real gait data of 34 patients with cerebrovascular accident with those of 15 healthy subjects), reliability, sensitivity, and specificity (applying a cluster analysis on the real data). Results showed for this method good appropriateness, 94.1% of sensitivity, 93.3% of specificity, and good reliability. The LFM resulted in a simple method suitable for analysing the waveform similarity in clinical gait analysis. PMID- 25126550 TI - Reduction of experimental cerebral malaria and its related proinflammatory responses by the novel liposome-based beta-methasone nanodrug. AB - Cerebral malaria (CM) is a severe complication of and a leading cause of death due to Plasmodium falciparum infection. CM is likely the result of interrelated events, including mechanical obstruction due to parasite sequestration in the microvasculature, and upregulation of Th1 immune responses. In parallel, blood brain-barrier (BBB) breakdown and damage or death of microglia, astrocytes, and neurons occurs. We found that a novel formulation of a liposome-encapsulated glucocorticosteroid, beta-methasone hemisuccinate (nSSL-BMS), prevents experimental cerebral malaria (ECM) in a murine model and creates a survival time window, enabling administration of an antiplasmodial drug before severe anemia develops. nSSL-BMS treatment leads to lower levels of cerebral inflammation, expressed by altered levels of corresponding cytokines and chemokines. The results indicate the role of integrated immune responses in ECM induction and show that the new steroidal nanodrug nSSL-BMS reverses the balance between the Th1 and Th2 responses in malaria-infected mice so that the proinflammatory processes leading to ECM are prevented. Overall, because of the immunopathological nature of CM, combined immunomodulator/antiplasmodial treatment should be considered for prevention/treatment of human CM and long-term cognitive damage. PMID- 25126549 TI - Cell death and inflammatory bowel diseases: apoptosis, necrosis, and autophagy in the intestinal epithelium. AB - Cell death mechanisms have been associated with the development of inflammatory bowel diseases in humans and mice. Recent studies suggested that a complex crosstalk between autophagy/apoptosis, microbe sensing, and enhanced endoplasmic reticulum stress in the epithelium could play a critical role in these diseases. In addition, necroptosis, a relatively novel programmed necrosis-like pathway associated with TNF receptor activation, seems to be also present in the pathogenesis of Crohn's disease and in specific animal models for intestinal inflammation. This review attempts to cover new data related to cell death mechanisms and inflammatory bowel diseases. PMID- 25126551 TI - Video game addiction in gambling disorder: clinical, psychopathological, and personality correlates. AB - OBJECTIVE: We studied the prevalences of video game use (VGU) and addiction (VGA) in gambling disorder (GD) patients and compared them with subjects with non-video game use (non-VGU) in relation to their gambling behavior, psychopathology, and personality characteristics. METHOD: A sample of 193 GD patients (121 non-VGU, 43 VGU, and 29 VGA) consecutively admitted to our pathological gambling unit participated in the study. Assessment. Measures included the video game dependency test (VDT), symptom checklist-90-revised, and the temperament and character inventory-revised, as well as a number of other GD indices. RESULTS: In GD, the observed prevalence of VG (use or addiction) was 37.3% (95% CI :30.7% / 44.3),VGU 22.3% (95% CI :17.0% / 28.7), and VGA 15% (95% CI :10.7% / 20.7). Orthogonal polynomial contrast into logistic regression showed positive linear trends for VG level and GD severity and other measures of general psychopathology. After structural equation modeling, higher VG total scores were associated with younger age, general psychopathology, and specific personality traits, but not with GD severity. Patients' sex and age were involved in the mediational pathways between personality traits and VG impairment. CONCLUSIONS: GD patients with VG are younger and present more dysfunctional personality traits, and more general psychopathology. The presence of VG did not affect the severity of GD. PMID- 25126552 TI - Role of nutrient-sensing signals in the pathogenesis of diabetic nephropathy. AB - Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. The multipronged drug approach still fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to improve the prognosis of diabetic nephropathy is urgently required. Nutrient sensing signals and their related intracellular machinery have evolved to combat prolonged periods of starvation in mammals; and these systems are conserved in the kidney. Recent studies have suggested that the activity of three nutrient sensing signals, mTORC1, AMPK, and Sirt1, is altered in the diabetic kidney. Furthermore, autophagy activity, which is regulated by the above-mentioned nutrient-sensing signals, is also altered in both podocytes and proximal tubular cells under diabetic conditions. Under diabetic conditions, an altered nutritional state owing to nutrient excess may disturb cellular homeostasis regulated by nutrient-responsible systems, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing relationships between nutrient-sensing signals, autophagy, and diabetic nephropathy and suggest the therapeutic potential of nutrient-sensing signals in diabetic nephropathy. PMID- 25126553 TI - Protection of coronary endothelial function during cardiac surgery: potential of targeting endothelial ion channels in cardioprotection. AB - Vascular endothelium plays a critical role in the control of blood flow by producing vasoactive factors to regulate vascular tone. Ion channels, in particular, K(+) channels and Ca(2+)-permeable channels in endothelial cells, are essential to the production and function of endothelium-derived vasoactive factors. Impairment of coronary endothelial function occurs in open heart surgery that may result in reduction of coronary blood flow and thus in an inadequate myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion during cardioplegic intervention compromise NO and EDHF-mediated function and the impairment involves alterations of K(+) channels, that is, KATP and KCa, and Ca(2+)-permeable TRP channels in endothelial cells. Pharmacological modulation of these channels during ischemia-reperfusion and hyperkalemic exposure show promising results on the preservation of NO and EDHF-mediated endothelial function, which suggests the potential of targeting endothelial K(+) and TRP channels for myocardial protection during cardiac surgery. PMID- 25126554 TI - Next generation delivery system for proteins and genes of therapeutic purpose: why and how? AB - Proteins and genes of therapeutic interests in conjunction with different delivery systems are growing towards new heights. "Next generation delivery systems" may provide more efficient platform for delivery of proteins and genes. In the present review, snapshots about the benefits of proteins or gene therapy, general procedures for therapeutic protein or gene delivery system, and different next generation delivery system such as liposome, PEGylation, HESylation, and nanoparticle based delivery have been depicted with their detailed explanation. PMID- 25126556 TI - Identifying the gene signatures from gene-pathway bipartite network guarantees the robust model performance on predicting the cancer prognosis. AB - For the purpose of improving the prediction of cancer prognosis in the clinical researches, various algorithms have been developed to construct the predictive models with the gene signatures detected by DNA microarrays. Due to the heterogeneity of the clinical samples, the list of differentially expressed genes (DEGs) generated by the statistical methods or the machine learning algorithms often involves a number of false positive genes, which are not associated with the phenotypic differences between the compared clinical conditions, and subsequently impacts the reliability of the predictive models. In this study, we proposed a strategy, which combined the statistical algorithm with the gene pathway bipartite networks, to generate the reliable lists of cancer-related DEGs and constructed the models by using support vector machine for predicting the prognosis of three types of cancers, namely, breast cancer, acute myeloma leukemia, and glioblastoma. Our results demonstrated that, combined with the gene pathway bipartite networks, our proposed strategy can efficiently generate the reliable cancer-related DEG lists for constructing the predictive models. In addition, the model performance in the swap analysis was similar to that in the original analysis, indicating the robustness of the models in predicting the cancer outcomes. PMID- 25126555 TI - Polymorphisms at amino acid residues 141 and 154 influence conformational variation in ovine PrP. AB - Polymorphisms in ovine PrP at amino acid residues 141 and 154 are associated with susceptibility to ovine prion disease: Leu141Arg154 with classical scrapie and Phe141Arg154 and Leu141His154 with atypical scrapie. Classical scrapie is naturally transmissible between sheep, whereas this may not be the case with atypical scrapie. Critical amino acid residues will determine the range or stability of structural changes within the ovine prion protein or its functional interaction with potential cofactors, during conversion of PrPC to PrPSc in these different forms of scrapie disease. Here we computationally identified that regions of ovine PrP, including those near amino acid residues 141 and 154, displayed more conservation than expected based on local structural environment. Molecular dynamics simulations showed these conserved regions of ovine PrP displayed genotypic differences in conformational repertoire and amino acid side chain interactions. Significantly, Leu141Arg154 PrP adopted an extended beta sheet arrangement in the N-terminal palindromic region more frequently than the Phe141Arg154 and Leu141His154 variants. We supported these computational observations experimentally using circular dichroism spectroscopy and immunobiochemical studies on ovine recombinant PrP. Collectively, our observations show amino acid residues 141 and 154 influence secondary structure and conformational change in ovine PrP that may correlate with different forms of scrapie. PMID- 25126557 TI - Antiulcerogenic potential activity of free and nanoencapsulated Passiflora serratodigitata L. extracts. AB - This paper provides evidence that the leaves and stem of Passiflora serratodigitata L. dry crude extract (DCE), ethylacetate fraction (EAF), and residual water fraction show potential antiulcerogenic activity. Interestingly, the polymeric nanocapsule loaded with EAF had 10-fold more activity than the free EAF. Furthermore, the polymer nanoparticles provided homogeneous colloidal drug delivery systems and allowed overcoming challenges such as poor aqueous solubility as well as the physical-chemical instability of the organic extract, which presented 90% (w/w) of the flavonoid content. The entrapment efficiency of the total flavonoid was 90.6 +/- 2.5% (w/v) for the DCE and 79.9 +/- 2.7% (w/v) for the EAF. This study shows that nanoencapsulation improves both the physicochemical properties and the efficacy of the herbal formulations. Therefore, free and encapsulated extracts have the potential to be suitable drug design candidates for the therapeutic management of ulcer. PMID- 25126558 TI - Microbiota in healthy skin and in atopic eczema. AB - The Italian interest group (IG) on atopic eczema and urticaria is member of the Italian Society of Allergology and Immunology. The aim of our IG is to provide a platform for scientists, clinicians, and experts. In this review we discuss the role of skin microbiota not only in healthy skin but also in skin suffering from atopic dermatitis (AD). A Medline and Embase search was conducted for studies evaluating the role of skin microbiota. We examine microbiota composition and its development within days after birth; we describe the role of specific groups of microorganisms that colonize distinct anatomical niches and the biology and clinical relevance of antimicrobial peptides expressed in the skin. Specific AD disease states are characterized by concurrent and anticorrelated shifts in microbial diversity and proportion of Staphylococcus. These organisms may protect the host, defining them not as simple symbiotic microbes but rather as mutualistic microbes. These findings reveal links between microbial communities and inflammatory diseases such as AD and provide novel insights into global shifts of bacteria relevant to disease progression and treatment. This review also highlights recent observations on the importance of innate immune systems and the relationship with normal skin microflora for the maintenance of healthy skin. PMID- 25126559 TI - Multiparametric MRI in biopsy guidance for prostate cancer: fusion-guided. AB - Prostate cancer (PCa) is the most common solid-organ malignancy among American men and the second most deadly. Current guidelines recommend a 12-core systematic biopsy following the finding of an elevated serum prostate-specific antigen (PSA). However, this strategy fails to detect an unacceptably high percentage of clinically significant cancers, leading researchers to develop new, innovative methods to improve the effectiveness of prostate biopsies. Multiparametric-MRI (MP-MRI) has emerged as a promising instrument in identifying suspicious regions within the prostate that require special attention on subsequent biopsy. Fusion platforms, which incorporate the MP-MRI into the biopsy itself and provide active targets within real-time imaging, have shown encouraging results in improving the detection rate of significant cancer. Broader applications of this technology, including MRI-guided focal therapy for prostate cancer, are in early phase trials. PMID- 25126560 TI - Aesthetic evaluation of the nasolabial region in children with unilateral cleft lip and palate comparing expert versus nonexperience health professionals. AB - Esthetic evaluation of cleft lip and palate rehabilitation outcomes may assist in the determination of new surgical interventions and aid in reevaluation of treatment protocols. Our objective was to compare esthetics assessments of the nasolabial region in children with a unilateral cleft lip and palate between healthcare professionals who were experienced in the treatment of cleft lip and palate and those who were inexperienced. The study group included 55 patients between 6 and 12 years of age who had already undergone primary reconstructive surgery for unilateral cleft lip. Standardized digital photographs were obtained, and the esthetic features of the nose, lip, and nasolabial region were evaluated. We used only cropped photographic images in the assessments of healthcare professionals with and without experience in cleft lip and palate. Interrater analysis revealed highly reliable assessments made by both the experienced and inexperienced professionals. There was no statistically significant difference in the esthetic attractiveness of the lip and nose between the experienced and inexperienced professionals. Compared with the inexperienced professionals, the experienced professional evaluators showed higher satisfaction with the esthetic appearance of the nasolabial region; however, no difference was observed in the analysis of the lip or nose alone. PMID- 25126562 TI - A novel promising strain of Trichoderma evansii (WF-3) for extracellular alpha galactosidase production by utilizing different carbon sources under optimized culture conditions. AB - A potential fungal strain of Trichoderma sp. (WF-3) was isolated and selected for the production of alpha-galactosidase. Optimum conditions for mycelial growth and enzyme induction were determined. Basal media selected for the growth of fungal isolate containing different carbon sources like guar gum (GG), soya bean meal (SM), and wheat straw (WS) and combinations of these carbon substrates with basic sugars like galactose and sucrose were used to monitor their effects on alpha galactosidase production. The results of this study indicated that galactose and sucrose enhanced the enzyme activity in guar gum (GG) and wheat straw (WS). Maximum alpha-galactosidase production (213.63 U mL(-1)) was obtained when the basic medium containing GG is supplemented with galactose (5 mg/mL). However, the presence of galactose and sucrose alone in the growth media shows no effect. Soya meal alone was able to support T. evansii to produce maximum enzyme activity (170.36 U mL(-1)). The incubation time, temperature, and pH for the maximum enzyme synthesis were found to be 120 h (5 days), 28 degrees C, and 4.5-5.5, respectively. All the carbon sources tested exhibited maximum enzyme production at 10 mg/mL concentration. Among the metal ions tested, Hg was found to be the strongest inhibitor of the enzyme. Among the chelators, EDTA acted as stronger inhibitor than succinic acid. PMID- 25126561 TI - The roles of CD73 in cancer. AB - Purinergic signaling has emerged as an important player in cancer progression and is regulated by a series of nucleotidases. Among the enzyme cascade, CD73, which catelyzes AMP breakdown to adenosine, has been found to be overexpressed in many types of cancer. Various factors and mechanisms are employed to regulate expression of CD73. Accumulating studies have shown that CD73 is a key regulatory molecule of cancer cells proliferation, migration and invasion in vitro, tumor angiogenesis, and tumor immune escape in vivo. With such important roles in cancer, CD73 has become an appealing therapy target. Recent evidences in mice models demonstrated that targeted blockade of CD73 could be a favorable therapeutic approach for cancer patients in the future. In this review, we will summarize the multiple roles of CD73 in cancer development, including its clinical significance, its promotive effects on tumor growth, metastasis, and angiogenesis, and its suppressive effects on immune response, regulatory mechanisms of CD73 expression, and current situation of anti-CD73 cancer therapy. PMID- 25126563 TI - Modulation of TLR 3, 7 and 8 expressions in HCV genotype 3 infected individuals: potential correlations of pathogenesis and spontaneous clearance. AB - BACKGROUND: Hepatitis C virus is the major cause of chronic hepatitis worldwide which finally leads to the development of hepatocellular carcinoma. Toll like receptors (TLRs) play an important role in the course of many viral infections, but the role of TLRs in HCV pathogenesis has not been well elucidated so far. OBJECTIVE: The aim of this study was to analyse the mRNA expression of TLRs 3, 7, and 8 in different stages of HCV infection including chronic, cirrhosis, interferon treated resolved, and relapsed cases. METHODOLOGY: Total RNA from whole blood was extracted and mRNA expression of TLRs 3, 7, and 8 genes was analyzed by quantitative real-time RT-PCR using beta-Actin gene as an internal control. RESULTS: This study consisted of 100 HCV infected individuals and twenty healthy controls. TLR 3 expression was found to be significantly elevated in individuals who had spontaneously cleared the virus (p < 0.001), whereas TLR 7 was found to be 3.26 times more elevated in patients with cirrhosis of liver. In IFN induced individuals, TLR 8 expression levels were found to be 2.28-fold elevated as compared to control population. CONCLUSION: TLRs 3, 7, and 8 are prime biomarker candidates for HCV infection mRNA expression analysis which might improve current therapeutic approaches. PMID- 25126565 TI - Definition of metrics to evaluate cochlear array insertion forces performed with forceps, insertion tool, or motorized tool in temporal bone specimens. AB - INTRODUCTION: In order to achieve a minimal trauma to the inner ear structures during array insertion, it would be suitable to control insertion forces. The aim of this work was to compare the insertion forces of an array insertion into anatomical specimens with three different insertion techniques: with forceps, with a commercial tool, and with a motorized tool. MATERIALS AND METHODS: Temporal bones have been mounted on a 6-axis force sensor to record insertion forces. Each temporal bone has been inserted, with a lateral wall electrode array, in random order, with each of the 3 techniques. RESULTS: Forceps manual and commercial tool insertions generated multiple jerks during whole length insertion related to fits and starts. On the contrary, insertion force with the motorized tool only rose at the end of the insertion. Overall force momentum was 1.16 +/- 0.505 N (mean +/- SD, n = 10), 1.337 +/- 0.408 N (n = 8), and 1.573 +/- 0.764 N (n = 8) for manual insertion with forceps and commercial and motorized tools, respectively. CONCLUSION: Considering force momentum, no difference between the three techniques was observed. Nevertheless, a more predictable force profile could be observed with the motorized tool with a smoother rise of insertion forces. PMID- 25126567 TI - Skin cancer, irradiation, and sunspots: the solar cycle effect. AB - Skin cancer is diagnosed in more than 2 million individuals annually in the United States. It is strongly associated with ultraviolet exposure, with melanoma risk doubling after five or more sunburns. Solar activity, characterized by features such as irradiance and sunspots, undergoes an 11-year solar cycle. This fingerprint frequency accounts for relatively small variation on Earth when compared to other uncorrelated time scales such as daily and seasonal cycles. Kolmogorov-Zurbenko filters, applied to the solar cycle and skin cancer data, separate the components of different time scales to detect weaker long term signals and investigate the relationships between long term trends. Analyses of crosscorrelations reveal epidemiologically consistent latencies between variables which can then be used for regression analysis to calculate a coefficient of influence. This method reveals that strong numerical associations, with correlations >0.5, exist between these small but distinct long term trends in the solar cycle and skin cancer. This improves modeling skin cancer trends on long time scales despite the stronger variation in other time scales and the destructive presence of noise. PMID- 25126566 TI - KPG index versus OPG measurements: a comparison between 3D and 2D methods in predicting treatment duration and difficulty level for patients with impacted maxillary canines. AB - AIM: The aim of this study was to test the agreement between orthopantomography (OPG) based 2D measurements and the KPG index, a new index based on 3D Cone Beam Computed Tomography (CBCT) images, in predicting orthodontic treatment duration and difficulty level of impacted maxillary canines. MATERIALS AND METHODS: OPG and CBCT images of 105 impacted canines were independently scored by three orthodontists at t 0 and after 1 month (t 1), using the KPG index and the following 2D methods: distance from cusp tip and occlusal plane, cusp tip position in relation to the lateral incisor, and canine inclination. Pearson's coefficients were used to evaluate the degree of agreement and the chi(2) with Yates correction test was used to assess the independence between them. RESULTS: Inter- and intrarater reliability were higher with KPG compared to 2D methods. Pearson's coefficients showed a statistically significant association between all the indexes, while the chi(2) with Yates correction test resulted in a statistically significant rejection of independency only for one 2D index. CONCLUSIONS: 2D indexes for predicting impacted maxillary canines treatment duration and difficulty sometimes are discordant; a 3D index like the KPG index could be useful in solving these conflicts. PMID- 25126568 TI - Depletion of arginine by recombinant arginine deiminase induces nNOS-activated neurotoxicity in neuroblastoma cells. AB - The abnormal regulation of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) is associated with neurodegenerative disorders. Recombinant arginine deiminase (rADI) is a selective NO modulator of iNOS and eNOS in endothelial cells, and it also exhibits neuroprotective activity in an iNOS-induced neuron-microglia coculture system. However, the effect of rADI on nNOS remains unknown. Addressing this issue is important for evaluating the potential application of rADI in neurodegenerative diseases. SH-SY5Y cells were treated with N-methyl-D-aspartic acid (NMDA) to activate nNOS. NMDA increased NO production by 39.7 +/- 3.9% via nNOS under arginine-containing conditions, but there was no significant increase in both arginine-free and rADI pretreated arginine-containing (citrulline) buffer. Subsequently, neither NMDA nor rADI alone caused cytotoxicity, whereas cotreatment with NMDA and rADI resulted in dissipation of the cell mitochondrial membrane potential and decreased cell viability. The mechanism of rADI cytotoxicity in the presence of NMDA is caused by the inhibition of NO production via nNOS mediated by the NMDA receptor, which was abolished when extracellular arginine was absent, even in the presence of citrulline. rADI not only reduced NO production but also caused cellular toxicity in nNOS-activated SH-SY5Y cells, suggesting a dual role for rADI in NOS-mediated neurotoxicity. PMID- 25126570 TI - PPI network analysis of mRNA expression profile of ezrin knockdown in esophageal squamous cell carcinoma. AB - Ezrin, coding protein EZR which cross-links actin filaments, overexpresses and involves invasion, metastasis, and poor prognosis in various cancers including esophageal squamous cell carcinoma (ESCC). In our previous study, Ezrin was knock down and analyzed by mRNA expression profile which has not been fully mined. In this study, we applied protein-protein interactions (PPI) network knowledge and methods to explore our understanding of these differentially expressed genes (DEGs). PPI subnetworks showed that hundreds of DEGs interact with thousands of other proteins. Subcellular localization analyses found that the DEGs and their directly or indirectly interacting proteins distribute in multiple layers, which was applied to analyze the shortest paths between EZR and other DEGs. Gene ontology annotation generated a functional annotation map and found hundreds of significant terms, especially those associated with cytoskeleton organization of Ezrin protein, such as "cytoskeleton organization," "regulation of actin filament based process," and "regulation of actin cytoskeleton organization." The algorithm of Random Walk with Restart was applied to prioritize the DEGs and identified several cancer related DEGs ranked closest to EZR. These analyses based on PPI network have greatly expanded our comprehension of the mRNA expression profile of Ezrin knockdown for future examination of the roles and mechanisms of Ezrin. PMID- 25126571 TI - Mass spectrometry based proteomic analysis of salivary glands of urban malaria vector Anopheles stephensi. AB - Salivary gland proteins of Anopheles mosquitoes offer attractive targets to understand interactions with sporozoites, blood feeding behavior, homeostasis, and immunological evaluation of malaria vectors and parasite interactions. To date limited studies have been carried out to elucidate salivary proteins of An. stephensi salivary glands. The aim of the present study was to provide detailed analytical attributives of functional salivary gland proteins of urban malaria vector An. stephensi. A proteomic approach combining one-dimensional electrophoresis (1DE), ion trap liquid chromatography mass spectrometry (LC/MS/MS), and computational bioinformatic analysis was adopted to provide the first direct insight into identification and functional characterization of known salivary proteins and novel salivary proteins of An. stephensi. Computational studies by online servers, namely, MASCOT and OMSSA algorithms, identified a total of 36 known salivary proteins and 123 novel proteins analysed by LC/MS/MS. This first report describes a baseline proteomic catalogue of 159 salivary proteins belonging to various categories of signal transduction, regulation of blood coagulation cascade, and various immune and energy pathways of An. stephensi sialotranscriptome by mass spectrometry. Our results may serve as basis to provide a putative functional role of proteins in concept of blood feeding, biting behavior, and other aspects of vector-parasite host interactions for parasite development in anopheline mosquitoes. PMID- 25126569 TI - Collagen VI and hyaluronan: the common role in breast cancer. AB - Collagen VI and hyaluronan are widely distributed extracellular matrix macromolecules that play a crucial role in tissue development and are highly expressed in cancers. Both hyaluronan and collagen VI are upregulated in breast cancer, generating a microenvironment that promotes tumour progression and metastasis. A growing number of studies show that these two molecules are involved in inflammation and angiogenesis by recruiting macrophages and endothelial cells, respectively. Additionally, collagen VI induces epithelial mesenchymal transition that is correlated to increased synthesis of hyaluronan in mammary cells. Hyaluronan has also a specific role in cellular functions that depends mainly on the size of the polymer, whereas the effect of collagen VI in tumour progression may be the result of the intact molecule or the C5 peptide of alpha3(VI) chain, known as endotrophin. Collectively, these findings strongly support the parallel role of these molecules in tumour progression and suggest that they may be used as prognostic factors for the breast cancer treatment. PMID- 25126572 TI - Metabolic modeling of common Escherichia coli strains in human gut microbiome. AB - The recent high-throughput sequencing has enabled the composition of Escherichia coli strains in the human microbial community to be profiled en masse. However, there are two challenges to address: (1) exploring the genetic differences between E. coli strains in human gut and (2) dynamic responses of E. coli to diverse stress conditions. As a result, we investigated the E. coli strains in human gut microbiome using deep sequencing data and reconstructed genome-wide metabolic networks for the three most common E. coli strains, including E. coli HS, UTI89, and CFT073. The metabolic models show obvious strain-specific characteristics, both in network contents and in behaviors. We predicted optimal biomass production for three models on four different carbon sources (acetate, ethanol, glucose, and succinate) and found that these stress-associated genes were involved in host-microbial interactions and increased in human obesity. Besides, it shows that the growth rates are similar among the models, but the flux distributions are different, even in E. coli core reactions. The correlations between human diabetes-associated metabolic reactions in the E. coli models were also predicted. The study provides a systems perspective on E. coli strains in human gut microbiome and will be helpful in integrating diverse data sources in the following study. PMID- 25126564 TI - Human genetic disorders and knockout mice deficient in glycosaminoglycan. AB - Glycosaminoglycans (GAGs) are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases and sulfotransferases. The structural diversity of GAG polysaccharides, including their sulfation patterns and sequential arrangements, is essential for a wide range of biological activities such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Studies using knockout mice of enzymes responsible for the biosynthesis of the GAG side chains of proteoglycans have revealed their physiological functions. Furthermore, mutations in the human genes encoding glycosyltransferases, sulfotransferases, and related enzymes responsible for the biosynthesis of GAGs cause a number of genetic disorders including chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This review focused on the increasing number of glycobiological studies on knockout mice and genetic diseases caused by disturbances in the biosynthetic enzymes for GAGs. PMID- 25126573 TI - First record of isolation and characterization of methicillin resistant Staphylococcus lugdunensis from clinical samples in Iraq. AB - This study was conducted to determine the frequency of Staphylococcus lugdunensis in different clinical samples. Out of 690 clinical samples, a total of 178 coagulase negative staphylococci (CoNS) isolates were recovered. CoNS were identified as 10 different species; 22 isolates belonged to Staphylococcus lugdunensis. Two specific genes for S. lugdunensis were used (tanA gene and fbl gene) to confirm identification. Both of these specific genes were detected in 15 (68.1%) of 22 isolates that were identified phenotypically. The results of oxacillin MIC showed that 7 of the 15 (46.6%) S. lugdunensis isolates were oxacillin resistant. The antibiotic susceptibility testing against 16 antibiotics showed that resistance rates were variable towards these antibiotics. Eight of fifteen S. lugdunensis isolates (53.3%) were beta-lactamase producer. Results of molecular detection of mecA gene found that mecA gene was detected in 6 (40%) of 15 S. lugdunensis. All of these 6 isolates (S1, S2, S3, S4, S5, and S6) were resistant to oxacillin. One isolate (S7) was resistant to oxacillin but mecA was not detected in this isolate. This study is a first record of isolation and characterization of methicillin resistant S. lugdunensis (MRSL) from clinical samples in Iraq. PMID- 25126574 TI - Blood monocyte subsets and selected cardiovascular risk markers in rheumatoid arthritis of short duration in relation to disease activity. AB - OBJECTIVES: To evaluate blood monocyte subsets and functional monocyte properties in patients with rheumatoid arthritis (RA) of short duration in the context of cardiovascular (CV) risk and disease activity. METHODS: We studied conventional markers of CV risk, intima media thickness (IMT), and blood monocyte subsets in 27 patients aged 41 +/- 10 years with RA of short duration (median 12 months) and 22 healthy controls. The RA subjects were divided into low (DAS28: 2.6-5.1) and high (DAS28 > 5.1) disease activity. RESULTS: RA patients exhibited increased levels of intermediate (CD14(++)CD16(+)) monocytes with decreased CD45RA expression compared to controls, increased counts of classical (CD14(++)CD16(-)) monocytes, and decreased percentages of nonclassical (CD14(+)CD16(++)) monocytes. Patients with high disease activity had lower HLA DR expression on classical monocytes compared to low disease activity patients. There were no differences in monocyte subsets between subjects with DAS > 5.1 and DAS <= 5.1. There were no significant intergroup differences in IMT and the majority of classical CV risk factors. CONCLUSIONS: Patients with RA of short duration show alteration in peripheral blood monocyte subsets despite the fact that there is no evidence of subclinical atherosclerosis. Disease activity assessed with DAS28 was associated with impaired functional properties but not with a shift in monocyte subpopulations. PMID- 25126576 TI - Biomechanical analysis of force distribution in human finger extensor mechanisms. AB - The complexities of the function and structure of human fingers have long been recognised. The in vivo forces in the human finger tendon network during different activities are critical information for clinical diagnosis, surgical treatment, prosthetic finger design, and biomimetic hand development. In this study, we propose a novel method for in vivo force estimation for the finger tendon network by combining a three-dimensional motion analysis technique and a novel biomechanical tendon network model. The extensor mechanism of a human index finger is represented by an interconnected tendinous network moving around the phalanx's dorsum. A novel analytical approach based on the "Principle of Minimum Total Potential Energy" is used to calculate the forces and deformations throughout the tendon network of the extensor mechanism when subjected to an external load and with the finger posture defined by measurement data. The predicted deformations and forces in the tendon network are in broad agreement with the results obtained by previous experimental in vitro studies. The proposed methodology provides a promising tool for investigating the biomechanical function of complex interconnected tendon networks in vivo. PMID- 25126575 TI - Store-operated Ca2+ entry does not control proliferation in primary cultures of human metastatic renal cellular carcinoma. AB - Store-operated Ca(2+) entry (SOCE) is activated following depletion of the inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca(2+) pool to regulate proliferation in immortalized cell lines established from either primary or metastatic lesions. The molecular nature of SOCE may involve both Stim1, which senses Ca(2+) levels within the endoplasmic reticulum (ER) Ca(2+) reservoir, and a number of a Ca(2+)-permeable channels on the plasma membrane, including Orai1, Orai3, and members of the canonical transient receptor (TRPC1-7) family of ion channels. The present study was undertaken to assess whether SOCE is expressed and controls proliferation in primary cultures isolated from secondary lesions of heavily pretreated metastatic renal cell carcinoma (mRCC) patients. SOCE was induced following pharmacological depletion of the ER Ca(2+) store, but not by InsP3-dependent Ca(2+) release. Metastatic RCC cells express Stim1-2, Orai1-3, and TRPC1-7 transcripts and proteins. In these cells, SOCE was insensitive to BTP 2, 10 uM Gd(3+) and Pyr6, while it was inhibited by 100 uM Gd(3+), 2-APB, and carboxyamidotriazole (CAI). Neither Gd(3+) nor 2-APB or CAI impaired mRCC cell proliferation. Consistently, no detectable Ca(2+) signal was elicited by growth factor stimulation. Therefore, a functional SOCE is expressed but does not control proliferation of mRCC cells isolated from patients resistant to multikinase inhibitors. PMID- 25126578 TI - Movement type prediction before its onset using signals from prefrontal area: an electrocorticography study. AB - Power changes in specific frequency bands are typical brain responses during motor planning or preparation. Many studies have demonstrated that, in addition to the premotor, supplementary motor, and primary sensorimotor areas, the prefrontal area contributes to generating such responses. However, most brain computer interface (BCI) studies have focused on the primary sensorimotor area and have estimated movements using postonset period brain signals. Our aim was to determine whether the prefrontal area could contribute to the prediction of voluntary movement types before movement onset. In our study, electrocorticography (ECoG) was recorded from six epilepsy patients while performing two self-paced tasks: hand grasping and elbow flexion. The prefrontal area was sufficient to allow classification of different movements through the area's premovement signals (-2.0 s to 0 s) in four subjects. The most pronounced power difference frequency band was the beta band (13-30 Hz). The movement prediction rate during single trial estimation averaged 74% across the six subjects. Our results suggest that premovement signals in the prefrontal area are useful in distinguishing different movement tasks and that the beta band is the most informative for prediction of movement type before movement onset. PMID- 25126577 TI - MicroRNA expression in salivary supernatant of patients with pancreatic cancer and its relationship with ZHENG. AB - In traditional Chinese medicine (TCM), diagnosis and prescriptions are based on the signs and symptoms which are recognized as ZHENG. The cornerstone of TCM is to differentially treat one ZHENG from others, which is also known as syndrome differentiation, and this relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, the expressions of 384 cancer-related miRNAs in salivary supernatant of patients with pancreatic cancer were assessed by miRNA polymerase chain reaction (PCR) array, and the different expression patterns of miRNA in three different groups of ZHENG were studied with use of real-time quantitative PCR (qRT-PCR). Some miRNAs were found to be specifically expressed in some ZHENGs, for instance, miR-17, miR-21, and miR-181b in Shi-Re ZHENG and miR-196a in Pi-Xu ZHENG. This indicates that these miRNAs may play important roles in different ZHENG condition. Therefore, this study to some extent revealed the molecular basis of TCM ZHENG in pancreatic cancer. PMID- 25126579 TI - The definition of a prolonged intensive care unit stay for spontaneous intracerebral hemorrhage patients: an application with national health insurance research database. AB - INTRODUCTION: Length of stay (LOS) in the intensive care unit (ICU) of spontaneous intracerebral hemorrhage (sICH) patients is one of the most important issues. The disease severity, psychosocial factors, and institutional factors will influence the length of ICU stay. This study is used in the Taiwan National Health Insurance Research Database (NHIRD) to define the threshold of a prolonged ICU stay in sICH patients. METHODS: This research collected the demographic data of sICH patients in the NHIRD from 2005 to 2009. The threshold of prolonged ICU stay was calculated using change point analysis. RESULTS: There were 1599 sICH patients included. A prolonged ICU stay was defined as being equal to or longer than 10 days. There were 436 prolonged ICU stay cases and 1163 nonprolonged cases. CONCLUSION: This study showed that the threshold of a prolonged ICU stay is a good indicator of hospital utilization in ICH patients. Different hospitals have their own different care strategies that can be identified with a prolonged ICU stay. This indicator can be improved using quality control methods such as complications prevention and efficiency of ICU bed management. Patients' stay in ICUs and in hospitals will be shorter if integrated care systems are established. PMID- 25126580 TI - Using ecological momentary assessment to evaluate current physical activity. AB - OBJECTIVE: The purpose of this study was to assess the value of ecological momentary assessment in evaluating physical activity among children, adolescents, and adults. It also determines whether ecological momentary assessment fulfills the criteria of validity, reliability, objectivity, norms, and standardization applied to the tools used for the evaluation of physical activity. METHODS: The EBSCO-CINHAL, Medline, PsycINFO, PubMed, and SPORTDiscuss databases were reviewed in December 2012 for articles associated with EMA. RESULTS: Of the 20 articles examined, half (10) used electronic methods for data collection, although various methods were used, ranging from pen and paper to smartphone applications. Ten studies used objective monitoring equipment. Nineteen studies were performed over 4 days. While the validity of the EMA method was discussed in 18 studies, only four found it to be objective. In all cases, the EMA procedures were precisely documented and confirmed to be feasible. CONCLUSIONS: Ecological momentary assessment is a valid, reliable, and feasible approach to evaluate activity and sedentary behavior. Researchers should be aware that while ecological momentary assessment offers many benefits, it simultaneously imposes many limitations which should be considered when studying physical activity. PMID- 25126581 TI - Patient outcomes following subarachnoid hemorrhage between the medical center and regional hospital: whether all patients should be transferred to medical centers. AB - Subarachnoid hemorrhage (SAH) is a critical illness that may result in patient mortality or morbidity. In this study, we investigated the outcomes of patients treated in medical center and nonmedical center hospitals and the relationship between such outcomes and hospital and surgeon volume. Patient data were abstracted from the National Health Insurance Research Database of Taiwan in the Longitudinal Health Insurance Database 2000, which contains all claims data of 1 million beneficiaries randomly selected in 2000. The International Classification of Diseases, Ninth Revision, subarachnoid hemorrhage (430) was used for the inclusion criteria. We identified 355 patients between 11 and 87 years of age who had subarachnoid hemorrhage. Among them, 32.4% (115/355) were men. The median Charlson comorbidity index (CCI) score was 1.3 (SD +/- 0.6). Unadjusted logistic regression analysis demonstrated that low mortality was associated with high hospital volume (OR = 3.21; 95% CI: 1.18-8.77). In this study, we found no statistical significances of mortality, LOS, and total charges between medical centers and nonmedical center hospitals. Patient mortality was associated with hospital volume. Nonmedical center hospitals could achieve resource use and outcomes similar to those of medical centers with sufficient volume. PMID- 25126582 TI - Ethical and legal implications of elective ventilation and organ transplantation: "medicalization" of dying versus medical mission. AB - A critical controversy surrounds the type of allowable interventions to be carried out in patients who are potential organ donors, in an attempt to improve organ perfusion and successful transplantation. The main goal is to transplant an organ in conditions as close as possible to its physiological live state. "Elective ventilation" (EV), that is, the use of ventilation for the sole purpose of retrieving the organs of patients close to death, is an option which offsets the shortage of organ donation. We have analyzed the legal context of the dying process of the organ donor and the feasibility of EV in the Italian context. There is no legal framework regulating the practice of EV, neither is any real information given to the general public. A public debate has yet to be initiated. In the Italian cultural and legislative scenario, we believe that, under some circumstances (i.e., the expressed wishes of the patient, even in the form of advance directives), the use of EV does not violate the principle of beneficence. We believe that the crux of the matter lies in the need to explore the real determination and will of the patient and his/her orientation towards the specific aim of organ donation. PMID- 25126584 TI - Potential and limitation of HLA-based banking of human pluripotent stem cells for cell therapy. AB - Great hopes have been placed on human pluripotent stem (hPS) cells for therapy. Tissues or organs derived from hPS cells could be the best solution to cure many different human diseases, especially those who do not respond to standard medication or drugs, such as neurodegenerative diseases, heart failure, or diabetes. The origin of hPS is critical and the idea of creating a bank of well characterized hPS cells has emerged, like the one that already exists for cord blood. However, the main obstacle in transplantation is the rejection of tissues or organ by the receiver, due to the three main immunological barriers: the human leukocyte antigen (HLA), the ABO blood group, and minor antigens. The problem could be circumvented by using autologous stem cells, like induced pluripotent stem (iPS) cells, derived directly from the patient. But iPS cells have limitations, especially regarding the disease of the recipient and possible difficulties to handle or prepare autologous iPS cells. Finally, reaching standards of good clinical or manufacturing practices could be challenging. That is why well-characterized and universal hPS cells could be a better solution. In this review, we will discuss the interest and the feasibility to establish hPS cells bank, as well as some economics and ethical issues. PMID- 25126583 TI - Glioma-associated antigen HEATR1 induces functional cytotoxic T lymphocytes in patients with glioma. AB - A2B5+ glioblastoma (GBM) cells have glioma stem-like cell (GSC) properties that are crucial to chemotherapy resistance and GBM relapse. T-cell-based antigens derived from A2B5+ GBM cells provide important information for immunotherapy. Here, we show that HEAT repeat containing 1 (HEATR1) expression in GBM tissues was significantly higher than that in control brain tissues. Furthermore, HEATR1 expression in A2B5+ U87 cells was higher than that in A2B5-U87 cells (P = 0.016). Six peptides of HEATR1 presented by HLA-A*02 were selected for testing of their ability to induce T-cell responses in patients with GBM. When peripheral blood mononuclear cells from healthy donors (n = 6) and patients with glioma (n = 33) were stimulated with the peptide mixture, eight patients with malignant gliomas had positive reactivity with a significantly increased number of responding T cells. The peptides HEATR(1682-690), HEATR(11126-1134), and HEATR(1757-765) had high affinity for binding to HLA-A*02:01 and a strong capacity to induce CTL response. CTLs against HEATR1 peptides were capable of recognizing and lysing GBM cells and GSCs. These data are the first to demonstrate that HEATR1 could induce specific CTL responses targeting both GBM cells and GSCs, implicating that HEATR1 peptide-based immunotherapy could be a novel promising strategy for treating patients with GBM. PMID- 25126585 TI - Cellular factors targeting APCs to modulate adaptive T cell immunity. AB - The fate of adaptive T cell immunity is determined by multiple cellular and molecular factors, among which the cytokine milieu plays the most important role in this process. Depending on the cytokines present during the initial T cell activation, T cells become effector cells that produce different effector molecules and execute adaptive immune functions. Studies thus far have primarily focused on defining how these factors control T cell differentiation by targeting T cells themselves. However, other non-T cells, particularly APCs, also express receptors for the factors and are capable of responding to them. In this review, we will discuss how APCs, by responding to those cytokines, influence T cell differentiation and adaptive immunity. PMID- 25126587 TI - The relevance of HLA sequencing in population genetics studies. AB - Next generation sequencing (NGS) is currently being adapted by different biotechnological platforms to the standard typing method for HLA polymorphism, the huge diversity of which makes this initiative particularly challenging. Boosting the molecular characterization of the HLA genes through efficient, rapid, and low-cost technologies is expected to amplify the success of tissue transplantation by enabling us to find donor-recipient matching for rare phenotypes. But the application of NGS technologies to the molecular mapping of the MHC region also anticipates essential changes in population genetic studies. Huge amounts of HLA sequence data will be available in the next years for different populations, with the potential to change our understanding of HLA variation in humans. In this review, we first explain how HLA sequencing allows a better assessment of the HLA diversity in human populations, taking also into account the methodological difficulties it introduces at the statistical level; secondly, we show how analyzing HLA sequence variation may improve our comprehension of population genetic relationships by facilitating the identification of demographic events that marked human evolution; finally, we discuss the interest of both HLA and genome-wide sequencing and genotyping in detecting functionally significant SNPs in the MHC region, the latter having also contributed to the makeup of the HLA molecular diversity observed today. PMID- 25126588 TI - Disease-Modifying Effect of Adiponectin in Model of alpha-Synucleinopathies. AB - OBJECTIVE: Growing evidence suggests that neurodegenerative diseases are associated with metabolic disorders, but the mechanisms are still unclear. Better comprehension of this issue might provide a new strategy for treatment of neurodegenerative diseases. We investigated possible roles of adiponectin (APN), the anti-diabetes protein, in the pathogenesis of alpha-synucleinopathies. METHODS: Using biochemical and histological methods, we investigated autopsy brain of alpha-synucleinopathies including Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and analyzed the effects of APN in cellular and in mouse models of alpha-synucleinopathies. RESULTS: We observed that APN is localized in Lewy bodies derived from alpha-synucleinopathies such as Parkinson's disease and dementia with Lewy bodies. In neuronal cells expressing alpha-synuclein (alphaS), aggregation of alphaS was suppressed by treatment with recombinant APN in an AdipoRI-AMP kinase pathway-dependent manner. Concomitantly, phosphorylation and release of alphaS were significantly decreased by APN, suggesting that APN may be antineurodegenerative. In transgenic mice expressing alphaS, both histopathology and movement disorder were significantly improved by intranasal treatment with globular APN when the treatment was initiated in the early stage of the disease. In a mouse model, reduced levels of guanosine- and inosine- monophosphates, both of which are potential stimulators of aggregation of alphaS, might partly contribute to suppression of aggregation of alphaS by APN. INTERPRETATION: Taken together, APN may suppress neurodegeneration through modification of the metabolic pathway, and could possess a therapeutic potential against alpha synucleinopathies. PMID- 25126590 TI - Mini-review: perspective of the microbiome in the pathogenesis of urothelial carcinoma. AB - The microbiome is a new center of attention for studies on the pathogenesis of human disease by focusing on the alterations of all microorganisms living in a particular site or system of human body, referred as microbiota. Evidence suggests that microbiota could contribute to the pathogenesis of a number of chronic diseases, including cancers, both locally and remotely. Multiple mechanisms have been proposed and/or proven for the microbiota's role in tumorigenesis, such as via induction of chronic inflammation, genotoxicity, bacterium-mediated cell proliferation, and activation of procarcinogens. Emerging data suggest that indigenous microbiota in the urinary tract may play an important role in the tumorigenesis of urothelial carcinoma, similar to other tumors. Future studies are needed to adequately define the microbiota composition and correlate its change with urothelial carcinoma. PMID- 25126589 TI - Gaining the Upper Hand on Pulmonary Drug Delivery. AB - Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF) are all pulmonary diseases which are characterized by chronic inflammation and an increase in mucus production. Excess mucus in the airways correlates with pathophysiology such as a decline in lung function and prolonged bacterial infections. New drugs to treat these chronic respiratory diseases are currently being developed and include both inhaled and orally administered compounds. Whilst oral drugs may be easier to administer, they are more prone to side effects due to higher bioavailability. Inhaled compounds may show reduced bioavailability, but face their own unique challenges. For example, thick mucus in the respiratory tracts of asthma, CF and COPD patients can act as a physical barrier that impedes drug delivery. Mucus also contains a high number of enzymes and proteases that may degrade compounds before they reach their site of action. Furthermore, some classes of drugs are rapidly absorbed across the respiratory epithelia into systemic circulation, which may limit their duration of action and/or cause off-target effects. This review discusses some of the different treatment options that are currently available and the considerations that need to be taken into account to produce new therapies for the treatment of chronic respiratory diseases. PMID- 25126586 TI - IL-6 as a druggable target in psoriasis: focus on pustular variants. AB - Psoriasis vulgaris (PV) is a cutaneous inflammatory disorder stemming from abnormal, persistent activation of the interleukin- (IL-)23/Th17 axis. Pustular psoriasis (PP) is a clinicopathological variant of psoriasis, histopathologically defined by the predominance of intraepidermal collections of neutrophils. Although PP pathogenesis is thought to largely follow that of (PV), recent evidences point to a more central role for IL-1, IL-36, and IL-6 in the development of PP. We review the role of IL-6 in the pathogenesis of PV and PP, focusing on its cross-talk with cytokines of the IL-23/Th17 axis. Clinical inhibitors of IL-6 signaling, including tocilizumab, have shown significant effectiveness in the treatment of several inflammatory rheumatic diseases, including rheumatoid arthritis and juvenile idiopathic arthritis; accordingly, anti-IL-6 agents may potentially represent future promising therapies for the treatment of PP. PMID- 25126591 TI - Theranostic Profiling for Actionable Aberrations in Advanced High Risk Osteosarcoma with Aggressive Biology Reveals High Molecular Diversity: The Human Fingerprint Hypothesis. AB - The survival of patients with advanced osteosarcoma is poor with limited therapeutic options. There is an urgent need for new targeted therapies based on biomarkers. Recently, theranostic molecular profiling services for cancer patients by CLIA-certified commercial companies as well as in-house profiling in academic medical centers have expanded exponentially. We evaluated molecular profiles of patients with advanced osteosarcoma whose tumor tissue had been analyzed by one of the following methods: 1. 182-gene next-generation exome sequencing (Foundation Medicine, Boston, MA), 2. Immunohistochemistry (IHC)/PCR based panel (CARIS Target Now, Irving, Tx), 3.Comparative genome hybridization (Oncopath, San Antonio, TX). 4. Single-gene PCR assays, PTEN IHC (MDACC CLIA), 5. UT Houston morphoproteomics (Houston, TX). The most common actionable aberrations occur in the PI3K/PTEN/mTOR pathway. No patterns in genomic alterations beyond the above are readily identifiable, and suggest both high molecular diversity in osteosarcoma and the need for more analyses to define distinct subgroups of osteosarcoma defined by genomic alterations. Based on our preliminary observations we hypothesize that the biology of aggressive and the metastatic phenotype osteosarcoma at the molecular level is similar to human fingerprints, in that no two tumors are identical. Further large scale analyses of osteosarcoma samples are warranted to test this hypothesis. PMID- 25126592 TI - IDMA-based MAC protocol for satellite networks with consideration on channel quality. AB - In order to overcome the shortcomings of existing medium access control (MAC) protocols based on TDMA or CDMA in satellite networks, interleave division multiple access (IDMA) technique is introduced into satellite communication networks. Therefore, a novel wide-band IDMA MAC protocol based on channel quality is proposed in this paper, consisting of a dynamic power allocation algorithm, a rate adaptation algorithm, and a call admission control (CAC) scheme. Firstly, the power allocation algorithm combining the technique of IDMA SINR-evolution and channel quality prediction is developed to guarantee high power efficiency even in terrible channel conditions. Secondly, the effective rate adaptation algorithm, based on accurate channel information per timeslot and by the means of rate degradation, can be realized. What is more, based on channel quality prediction, the CAC scheme, combining the new power allocation algorithm, rate scheduling, and buffering strategies together, is proposed for the emerging IDMA systems, which can support a variety of traffic types, and offering quality of service (QoS) requirements corresponding to different priority levels. Simulation results show that the new wide-band IDMA MAC protocol can make accurate estimation of available resource considering the effect of multiuser detection (MUD) and QoS requirements of multimedia traffic, leading to low outage probability as well as high overall system throughput. PMID- 25126593 TI - Impacts of groundwater recharge from rubber dams on the hydrogeological environment in Luoyang Basin, China. AB - In the rubber dam's impact area, the groundwater total hardness (TH) has declined since 2000, ultimately dropping to 100-300 mg/L in 2012. pH levels have shown no obvious changes. NH4-N concentration in the groundwater remained stable from 2000 to 2006, but it increased from 2007 to 2012, with the largest increase up to 0.2 mg/L. NO3-N concentration in the groundwater generally declined in 2000-2006 and then increased from 2007; the largest increase was to 10 mg/L in 2012. Total dissolved solids (TDS) of the groundwater showed a general trend of decline from 2000 to 2009, but levels increased after 2010, especially along the south bank of the Luohe River where the largest increase recorded was approximately 100 mg/L. This study has shown that the increases in the concentrations of NH4-N and NO3-N were probably caused by changes in groundwater levels. Nitrates adsorbed by the silt clay of aeration zone appear to have entered the groundwater through physical and chemical reactions. TDS increased because of groundwater evaporation and some soluble ions entered the groundwater in the unsaturated zone. The distance of the contaminant to the surface of the aquifer became shorter due to the shallow depth of groundwater, resulting in the observed rise in pollutant concentrations more pronounced. PMID- 25126595 TI - Examination of the behavior of gravity quay wall against liquefaction under the effect of wall width and soil improvement. AB - Deformation of quay walls is one of the main sources of damage to port facility while liquefaction of backfill and base soil of the wall are the main reasons for failures of quay walls. During earthquakes, the most susceptible materials for liquefaction in seashore regions are loose saturated sand. In this study, effects of enhancing the wall width and the soil improvement on the behavior of gravity quay walls are examined in order to obtain the optimum improved region. The FLAC 2D software was used for analyzing and modeling progressed models of soil and loading under difference conditions. Also, the behavior of liquefiable soil is simulated by the use of "Finn" constitutive model in the analysis models. The "Finn" constitutive model is especially created to determine liquefaction phenomena and excess pore pressure generation. PMID- 25126594 TI - Cytotoxic constituents from the rhizomes of Curcuma zedoaria. AB - Curcuma zedoaria also known as Temu putih is traditionally used in food preparations and treatment of various ailments including cancer. The cytotoxic activity of hexane, dichloromethane, ethyl acetate, methanol, and the methanol soxhlet extracts of Curcuma zedoaria rhizomes was tested on two human cancer cell lines (Ca Ski and MCF-7) and a noncancer cell line (HUVEC) using MTT assay. Investigation on the chemical components in the hexane and dichloromethane fractions gave 19 compounds, namely, labda-8(17),12 diene-15,16 dial (1), dehydrocurdione (2), curcumenone (3), comosone II (4), curcumenol (5), procurcumenol (6), germacrone (7), zerumbone epoxide (8), zederone (9), 9 isopropylidene-2,6-dimethyl-11-oxatricyclo[6.2.1.0(1,5)]undec-6-en-8-ol (10), furanodiene (11), germacrone-4,5-epoxide (12), calcaratarin A (13), isoprocurcumenol (14), germacrone-1,10-epoxide (15), zerumin A (16), curcumanolide A (17), curcuzedoalide (18), and gweicurculactone (19). Compounds (1-19) were evaluated for their antiproliferative effect using MTT assay against four cancer cell lines (Ca Ski, MCF-7, PC-3, and HT-29). Curcumenone (3) and curcumenol (5) displayed strong antiproliferative activity (IC50 = 8.3 +/- 1.0 and 9.3 +/- 0.3 MUg/mL, resp.) and were found to induce apoptotic cell death on MCF-7 cells using phase contrast and Hoechst 33342/PI double-staining assay. Thus, the present study provides basis for the ethnomedical application of Curcuma zedoaria in the treatment of breast cancer. PMID- 25126597 TI - The modelled raindrop size distribution of Skudai, Peninsular Malaysia, using exponential and lognormal distributions. AB - This paper presents the modelled raindrop size parameters in Skudai region of the Johor Bahru, western Malaysia. Presently, there is no model to forecast the characteristics of DSD in Malaysia, and this has an underpinning implication on wet weather pollution predictions. The climate of Skudai exhibits local variability in regional scale. This study established five different parametric expressions describing the rain rate of Skudai; these models are idiosyncratic to the climate of the region. Sophisticated equipment that converts sound to a relevant raindrop diameter is often too expensive and its cost sometimes overrides its attractiveness. In this study, a physical low-cost method was used to record the DSD of the study area. The Kaplan-Meier method was used to test the aptness of the data to exponential and lognormal distributions, which were subsequently used to formulate the parameterisation of the distributions. This research abrogates the concept of exclusive occurrence of convective storm in tropical regions and presented a new insight into their concurrence appearance. PMID- 25126596 TI - Sequence variation in Toxoplasma gondii rop17 gene among strains from different hosts and geographical locations. AB - Genetic diversity of T. gondii is a concern of many studies, due to the biological and epidemiological diversity of this parasite. The present study examined sequence variation in rhoptry protein 17 (ROP17) gene among T. gondii isolates from different hosts and geographical regions. The rop17 gene was amplified and sequenced from 10 T. gondii strains, and phylogenetic relationship among these T. gondii strains was reconstructed using maximum parsimony (MP), neighbor-joining (NJ), and maximum likelihood (ML) analyses. The partial rop17 gene sequences were 1375 bp in length and A+T contents varied from 49.45% to 50.11% among all examined T. gondii strains. Sequence analysis identified 33 variable nucleotide positions (2.1%), 16 of which were identified as transitions. Phylogeny reconstruction based on rop17 gene data revealed two major clusters which could readily distinguish Type I and Type II strains. Analyses of sequence variations in nucleotides and amino acids among these strains revealed high ratio of nonsynonymous to synonymous polymorphisms (>1), indicating that rop17 shows signs of positive selection. This study demonstrated the existence of slightly high sequence variability in the rop17 gene sequences among T. gondii strains from different hosts and geographical regions, suggesting that rop17 gene may represent a new genetic marker for population genetic studies of T. gondii isolates. PMID- 25126599 TI - Influence of vacancy defect on surface feature and adsorption of Cs on GaN(0001) surface. AB - The effects of Ga and N vacancy defect on the change in surface feature, work function, and characteristic of Cs adsorption on a (2 * 2) GaN(0001) surface have been investigated using density functional theory with a plane-wave ultrasoft pseudopotential method based on first-principles calculations. The covalent bonds gain strength for Ga vacancy defect, whereas they grow weak for N vacancy defect. The lower work function is achieved for Ga and N vacancy defect surfaces than intact surface. The most stable position of Cs adatom on Ga vacancy defect surface is at T1 site, whereas it is at B(Ga) site on N vacancy defect surface. The E(ads) of Cs on GaN(0001) vacancy defect surface increases compared with that of intact surface; this illustrates that the adsorption of Cs on intact surface is more stable. PMID- 25126598 TI - The influence of obesity on different genders in patients with obstructive sleep apnea. AB - Obesity is considered to be a major contributing factor to obstructive sleep apnea (OSA); however, there is limited evidence with regard to gender predominance. We analyzed 2345 patients (339 females) in correlation with body mass index (BMI) and OSA severity. Male AHIs were significantly higher than female AHIs in each BMI group. As the BMI increased, the AHI increased in both males and females, and this trend was more obvious in males. For BMI-matched male and female patients with OSA, the severity of OSA was higher in males. As BMI increased, the severity of OSA increased more obviously in males. Our findings suggest that increased body fat contributes to the pathogenesis of OSA more in males than in females and that obesity plays a more significant role in contributing to OSA in male patients. PMID- 25126601 TI - Characterization of coal porosity for naturally tectonically stressed coals in Huaibei coal field, China. AB - The enrichment of coalbed methane (CBM) and the outburst of gas in a coal mine are closely related to the nanopore structure of coal. The evolutionary characteristics of 12 coal nanopore structures under different natural deformational mechanisms (brittle and ductile deformation) are studied using a scanning electron microscope (SEM) and low-temperature nitrogen adsorption. The results indicate that there are mainly submicropores (2~5 nm) and supermicropores (<2 nm) in ductile deformed coal and mesopores (10~100 nm) and micropores (5~10 nm) in brittle deformed coal. The cumulative pore volume (V) and surface area (S) in brittle deformed coal are smaller than those in ductile deformed coal which indicates more adsorption space for gas. The coal with the smaller pores exhibits a large surface area, and coal with the larger pores exhibits a large volume for a given pore volume. We also found that the relationship between S and V turns from a positive correlation to a negative correlation when S > 4 m(2)/g, with pore sizes <5 nm in ductile deformed coal. The nanopore structure (<100 nm) and its distribution could be affected by macromolecular structure in two ways. Interconversion will occur among the different size nanopores especially in ductile deformed coal. PMID- 25126602 TI - Large-area binary blazed grating coupler between nanophotonic waveguide and LED. AB - A large-area binary blazed grating coupler for the arrayed waveguide grating (AWG) demodulation integrated microsystem on silicon-on-insulator (SOI) was designed for the first time. Through the coupler, light can be coupled into the SOI waveguide from the InP-based C-band LED for the AWG demodulation integrated microsystem to function. Both the length and width of the grating coupler are 360 MUm, as large as the InP-based C-band LED light emitting area in the system. The coupler was designed and optimized based on the finite difference time domain method. When the incident angle of the light source is 0 degrees , the coupling efficiency of the binary blazed grating is 40.92%, and the 3 dB bandwidth is 72 nm at a wavelength of 1550 nm. PMID- 25126603 TI - A novel modulation classification approach using Gabor filter network. AB - A Gabor filter network based approach is used for feature extraction and classification of digital modulated signals by adaptively tuning the parameters of Gabor filter network. Modulation classification of digitally modulated signals is done under the influence of additive white Gaussian noise (AWGN). The modulations considered for the classification purpose are PSK 2 to 64, FSK 2 to 64, and QAM 4 to 64. The Gabor filter network uses the network structure of two layers; the first layer which is input layer constitutes the adaptive feature extraction part and the second layer constitutes the signal classification part. The Gabor atom parameters are tuned using Delta rule and updating of weights of Gabor filter using least mean square (LMS) algorithm. The simulation results show that proposed novel modulation classification algorithm has high classification accuracy at low signal to noise ratio (SNR) on AWGN channel. PMID- 25126604 TI - The potential of using brain images for authentication. AB - Biometric recognition (also known as biometrics) refers to the automated recognition of individuals based on their biological or behavioral traits. Examples of biometric traits include fingerprint, palmprint, iris, and face. The brain is the most important and complex organ in the human body. Can it be used as a biometric trait? In this study, we analyze the uniqueness of the brain and try to use the brain for identity authentication. The proposed brain-based verification system operates in two stages: gray matter extraction and gray matter matching. A modified brain segmentation algorithm is implemented for extracting gray matter from an input brain image. Then, an alignment-based matching algorithm is developed for brain matching. Experimental results on two data sets show that the proposed brain recognition system meets the high accuracy requirement of identity authentication. Though currently the acquisition of the brain is still time consuming and expensive, brain images are highly unique and have the potential possibility for authentication in view of pattern recognition. PMID- 25126605 TI - An analysis dictionary learning algorithm under a noisy data model with orthogonality constraint. AB - Two common problems are often encountered in analysis dictionary learning (ADL) algorithms. The first one is that the original clean signals for learning the dictionary are assumed to be known, which otherwise need to be estimated from noisy measurements. This, however, renders a computationally slow optimization process and potentially unreliable estimation (if the noise level is high), as represented by the Analysis K-SVD (AK-SVD) algorithm. The other problem is the trivial solution to the dictionary, for example, the null dictionary matrix that may be given by a dictionary learning algorithm, as discussed in the learning overcomplete sparsifying transform (LOST) algorithm. Here we propose a novel optimization model and an iterative algorithm to learn the analysis dictionary, where we directly employ the observed data to compute the approximate analysis sparse representation of the original signals (leading to a fast optimization procedure) and enforce an orthogonality constraint on the optimization criterion to avoid the trivial solutions. Experiments demonstrate the competitive performance of the proposed algorithm as compared with three baselines, namely, the AK-SVD, LOST, and NAAOLA algorithms. PMID- 25126606 TI - Dynamic response and optimal design of curved metallic sandwich panels under blast loading. AB - It is important to understand the effect of curvature on the blast response of curved structures so as to seek the optimal configurations of such structures with improved blast resistance. In this study, the dynamic response and protective performance of a type of curved metallic sandwich panel subjected to air blast loading were examined using LS-DYNA. The numerical methods were validated using experimental data in the literature. The curved panel consisted of an aluminum alloy outer face and a rolled homogeneous armour (RHA) steel inner face in addition to a closed-cell aluminum foam core. The results showed that the configuration of a "soft" outer face and a "hard" inner face worked well for the curved sandwich panel against air blast loading in terms of maximum deflection (MaxD) and energy absorption. The panel curvature was found to have a monotonic effect on the specific energy absorption (SEA) and a nonmonotonic effect on the MaxD of the panel. Based on artificial neural network (ANN) metamodels, multiobjective optimization designs of the panel were carried out. The optimization results revealed the trade-off relationships between the blast resistant and the lightweight objectives and showed the great use of Pareto front in such design circumstances. PMID- 25126607 TI - Graphs and matroids weighted in a bounded incline algebra. AB - Firstly, for a graph weighted in a bounded incline algebra (or called a dioid), a longest path problem (LPP, for short) is presented, which can be considered the uniform approach to the famous shortest path problem, the widest path problem, and the most reliable path problem. The solutions for LPP and related algorithms are given. Secondly, for a matroid weighted in a linear matroid, the maximum independent set problem is studied. PMID- 25126608 TI - A new kind of fuzzy n-ary hypergroups in the framework of soft set theory. AB - Maji et al. introduced the concept of fuzzy soft sets as a generalization of the standard soft sets and presented an application of fuzzy soft sets in a decision making problem. The aim of this paper is to apply the concept of fuzzy soft sets to n-ary hypergroup theory. The concepts of (?(gamma), ?(gamma) ? q(delta))-fuzzy soft (invertible) n-ary subhypergroups over a commutative n-ary hypergroup are introduced and some related properties and characterizations are obtained. The homomorphism properties of (?(gamma), ?(gamma) ? q(delta))-fuzzy soft (invertible) n-ary subhypergroups are also derived. PMID- 25126609 TI - Obtaining P3P privacy policies for composite services. AB - With the development of web services technology, web services have changed from single to composite services. Privacy protection in composite services is becoming an important issue. P3P (platform for privacy preferences) is a privacy policy language which was designed for single web services. It enables service providers to express how they will deal with the privacy information of service consumers. In order to solve the problem that P3P cannot be applied to composite services directly, we propose a method to obtain P3P privacy policies for composite services. In this method, we present the definitions of Purpose, Recipient, and Retention elements as well as Optional and Required attributes for P3P policies of composite services. We also provide an instantiation to illustrate the feasibility of the method. PMID- 25126610 TI - Mycotoxins and mycotoxigenic fungi in poultry feed for food-producing animals. AB - Moulds are capable of reducing the nutritional value of feedstuff as well as elaborating several mycotoxins. Mycotoxin-contaminated feed has adverse effects on animal health and productivity. Also, mycotoxins may be carried over into meat and eggs when poultry are fed with contaminated feed. In a point prevalence study feedstuff used for poultry nutrition in Argentina was analyzed for fungal flora, natural incidence of selected mycotoxins, and nutritional quality. Ten mould genera were recovered, six of them known to be mycotoxigenic. More than 28 species were determined. Fumonisins were detected in all the samples (median 1,750 ppb). Forty-four out of 49 samples (90%) were contaminated with DON (median 222 ppb) and OTA (median 5 ppb). Also, 44 out of 49 samples were contaminated with aflatoxins (median 2.685 ppb), 42 samples (86%) with ZEA (median 50 ppb), and 38 samples (78%) with T2-toxin (median 50 ppb). Ninety percent of the samples had at least one type of nutritional deficiency. This study indicates the need for continuous assessment of the mycological status of animal feed production, in order to feed animals for optimal performance ensuring food safety. PMID- 25126611 TI - Natural recovery and planned intervention in coastal wetlands: Venice Lagoon (northern Adriatic Sea, Italy) as a case study. AB - The goals of conservation and sustainable use of environmental ecosystems have increased the need for detailed knowledge of ecological evolution and responses to both anthropogenic pressures and recovery measures. The present study shows the effects of natural processes and planned intervention in terms of reducing nutrient inputs in a highly exploited coastal lagoon, describing its evolution over a 16-year period from the late 1980s (when eutrophication was at its peak) until 2003. Changes in nutrient and carbon concentrations in the top layer of sediments were investigated in parallel with macroalgal and seagrass biomass in the most anthropized basin of Venice Lagoon in four surveys conducted in accordance with the same protocols in 1987, 1993, 1998, and 2003. A pronounced reduction in trophic state (mainly total nitrogen, organic phosphorus, and organic carbon concentrations) and macroalgal biomass was recorded, together with the progressive expansion of seagrass meadows. General considerations are also made on the effects of Manila clam farming and the shift from illegal to managed clam farming. PMID- 25126613 TI - Cerebellar Ataxia and CoQ10 Deficiency. PMID- 25126614 TI - Toward the future. PMID- 25126612 TI - Voltage dependent anion channel is redistributed during Japanese encephalitis virus infection of insect cells. AB - Despite the availability of an effective vaccine, Japanese encephalitis remains a significant cause of morbidity and mortality in many parts of Asia. Japanese encephalitis is caused by the Japanese encephalitis virus (JEV), a mosquito transmitted flavivirus. Many of the details of the virus replication cycle in mosquito cells remain unknown. This study sought to determine whether GRP78, a well-characterized flavivirus E protein interacting protein, interacted with JEV E protein in insect cells, and whether this interaction was mediated at the cell surface. GRP78 was shown to interact with JEV E protein by coimmunoprecipitation, and was additionally shown to interact with voltage dependent anion protein (VDAC) through the same methodology. Antibody inhibition experiments showed that neither GRP78 nor VDAC played a role in JEV internalization to insect cells. Interestingly, VDAC was shown to be significantly relocalized in response to JEV infection, and significant levels of colocalization between VDAC and GRP78 and VDAC and ribosomal L28 protein were seen in JEV infected but not uninfected cells. This is the first report of relocalization of VDAC in response to JEV infection and suggests that this may be a part of the JEV replication strategy in insect cells. PMID- 25126615 TI - Bio-Emulation: biomimetically emulating nature utilizing a histoanatomic approach; visual synthesis. AB - A thorough understanding of the spatial distribution pertaining to the histo anatomic coronal structures and dynamic light interaction of the natural dentition provides the dental team with the ultimate strategic advantage with regards to optical integration of the final restoration. The second part of this two-part article will attempt to provide insight on the illumination interactivity and the spatial arrangement of the coronal elements of natural teeth through the utilization of this knowledge in the clinical and technical restorative approach. The main goals for this article are to cognize histo anatomic visualization by introducing: (1) Dynamic light interaction, (2) the 9 elements of visual synthesis, (3) dynamic infinite optical thickness, and (4) amplified visual perception effect of the hard dental tissues. Furthermore, a diversification of photographic illumination techniques will be illustrated in order to juxtapose optical associations between the enamel/dentinoenamel complex/dentin nexus. PMID- 25126616 TI - Ceramic adhesive restorations and biomimetic dentistry: tissue preservation and adhesion. AB - Thanks to sophisticated adhesive techniques in contemporary dentistry, and the development of composite and ceramic materials, it is possible to reproduce a biomimetic match between substitution materials and natural teeth substrates. Biomimetics or bio-emulation allows for the association of two fundamental parameters at the heart of current therapeutic treatments: tissue preservation and adhesion. This contemporary concept makes the retention of the integrity of the maximum amount of dental tissue possible, while offering exceptional clinical longevity, and maximum esthetic results. It permits the conservation of the biological, esthetic, biomechanical and functional properties of enamel and dentin. Today, it is clearly possible to develop preparations allowing for the conservation of the enamel and dentin in order to bond partial restorations in the anterior and posterior sectors therefore limiting, as Professor Urs Belser from Geneva indicates, "the replacement of previous deficient crowns and devitalized teeth whose conservation are justified but whose residual structural state are insufficient for reliable bonding."1 This article not only addresses ceramic adhesive restoration in the anterior area, the ambassadors of biomimetic dentistry, but also highlights the possibility of occasionally integrating one or two restorations at the heart of the smile as a complement to extensive rehabilitations that require more invasive treatment. PMID- 25126618 TI - Influence of enamel composite thickness on value, chroma and translucency of a high and a nonhigh refractive index resin composite. AB - OBJECTIVES: To evaluate the influence of thickness on the optical properties of two enamel shade composites, one with a high refractive index and one traditional. METHODS: A medium value enamel shade was selected from the resin composites Enamel Plus HRi (UE2) and Enamel Plus HFO (GE2). Enamel Plus HRi is a high refractive index composite. Samples were fabricated in five different thicknesses: 0.3, 0.5, 1, 1.5 and 2 mm. Three specimens per material and thickness were fabricated. Three measurements per sample, over white, black and dentin composite background were generated with a spectrophotometer (Spectroshade Micro, MHT). Value, chroma, translucency and color differences (DeltaE) of the specimens were calculated. RESULTS were analyzed by the Pearson correlation test, ANOVA and a post-hoc Tukey test. RESULTS: Increasing the thickness of the enamel layers decreased the translucency and the chroma of the substrate for both materials tested. For HRi the increase of the thickness resulted in an increase of the value, whereas for HFO it resulted in a reduction of the value. The two composites showed a significant difference in value for each thickness, but not in translucency and chroma. Color difference between them was perceptible in layers equal or higher than 0.5 mm. CONCLUSIONS: The high refractive index enamel (HRi) composite exhibits different optical behavior compared to the traditional one (HFO). HRi enamel composite behaves more like natural enamel as by increasing the thickness of the enamel layer, the value also increases. PMID- 25126617 TI - Anthropometric analysis of anterior maxillary teeth with digital photography - a study in a Portuguese sample. AB - SUMMARY: Establishing a geometrical pattern of the anterior maxillary sector has been attempted for a long time. The Golden Proportion, Preston's Percentage, Golden Percentage, Recurring Esthetic Dental (RED) Proportion and, most recently, Gauge Proportion, are theories that try to apply mathematical and geometrical relations to the anterior maxillary teeth. PURPOSE: To study the anterior maxillary teeth proportions of a Portuguese population sample and see if any of the existent anthropometric proportions can be applied to the oral rehabilitation of this population. MATERIALS AND METHODS: Standardized frontal and lateral images of 50 dental patient smiles included in the inclusion criteria were captured. The widths and heights of maxillary anterior teeth were measured using image-processing software and data were statistically analyzed using a parametric test (t test). RESULTS: The widths and heights were concordant with the values described by the Gauge Proportion. However, they were above the recommended value of 78% for the width/height proportion advocated. The proportions between the widths of the maxillary anterior teeth were not constant as proposed by the Golden Proportion and the RED Proportion. The Preston Proportion was found to be in concordance with the studied population. The values observed were closer to the Golden Percentage. Considering genre, there was a statistically significant difference. Male patients had teeth with larger dimensions than females. CONCLUSION: Within the limitations of this study, mainly concerned to the sample size, it may be concluded that the widths and heights of the anterior maxillary teeth were coincident with the Gauge Proportion. Both the Golden Proportion and the RED proportion are unsuitable methods to relate the widths of the maxillary anterior teeth unlike the Preston's Proportion. The Golden Percentage was close to the percentages observed and could be adjusted to be taken in consideration to this population. PMID- 25126619 TI - Treatment planning and dental rehabilitation of a periodontally compromised partially edentulous patient: a case report - Part I. AB - When planning a prosthetic rehabilitation of a periodontally compromised case, the clinician is often confronted with difficulties and dilemmas related to selecting the appropriate treatment modality that would provide a long-term longevity in terms of function and esthetics. In such cases, a correct diagnosis and prognosis of the intraoral situation supported by evidence-based dentistry is the basis for the establishment of a proper treatment strategy. In this two-part treatment planning series, a systematic approach of patient examination and prognosis of each tooth is presented. Furthermore, different removable and fixed treatment possibilities are described and the rationale governing the decision making process is revealed. The execution of the final treatment plan as specified by the concept of comprehensive dental care is outlined and the final outcome is discussed according to the literature. PMID- 25126620 TI - The effects of forehead and neck position on esthetics of class I, II and III profiles. AB - INTRODUCTION: All parts of the face, other than jaw relationships, should be considered in orthodontic treatment planning. The role of forehead and neck in facial esthetics is well known; however, the majority of conventional facial analysis methods have not considered them. Neck and forehead may confer mutual effects on equilibrium and on esthetics of other facial components, and may change the overall convexity/concavity view of the profile. Therefore, the aim of this study was to assess the effect of anteroposterior position of the forehead and neck on the esthetics of skeletal class I, II and III jaw relationships using profile silhouettes. METHODS: Class II and III jaw relationships were constructed on the silhouette of a class I normal profile by altering the mandibular position. Retruded, normal and protruded positions were also applied for the forehead and neck. Three hundred Iranian laypeople (150 men, 150 women) scored the esthetics of profile silhouettes from 1 to 7. Half of the participants were told to consider the profiles as a man, and the other half were told to consider them as a woman. Data were analyzed using non-parametric methods. RESULTS: Class I jaw relation was found to be the most beautiful profile followed by class II and III respectively. Esthetics of different positions of the neck and forehead were significantly different (P < 0.05). In subjects with a normal neck and forehead position, and those with a retruded neck, the best esthetic relationship was class I, and the worst was class III. For protruded foreheads, the best jaw relationship was class II for females and class I for males, and the worst was class III for both. In a retruded forehead position, the most preferred jaw relationship was class I, and the worst was class II. For profiles with a protruded neck, the best esthetics was found to be in class III jaw relationship, and the worst was in class II. There was a small difference in scoring for male and female profiles (P < 0.05); there were also small differences in scoring trends of men and women (P < 0.05). CONCLUSION: This study showed that the anteroposterior position of the forehead and neck affects the esthetics of jaw relationships in profile view. In laypeople's opinions, in a normal profile, the overall appearance is more important compared to the independent position of the neck and forehead; however, having jaw abnormalities, the neck plays an important independent role. The preferred jaw relation for profiles with each forehead or neck position was introduced. PMID- 25126621 TI - Comparison of marginal fit of Lava CAD/CAM crown-copings with two finish lines. AB - PURPOSE: Marginal fit is valued as one of the most important criteria for the clinical quality and success of all-ceramic crowns. The aim of this in vitro study was to investigate the marginal fit of Lava Zirconia crown-copings on chamfer and shoulder preparations. METHODS: Two acrylic model teeth were selected to simulate the clinical preparations: one molar was prepared with a chamfer finish line (C) and one premolar was prepared with a rounded shoulder finish line (RS). Each resin model was duplicated 10 times using silicon-based impression material and poured in type IV dental stone for the fabrication of working dies. A total of 20 copings were divided into two groups (n = 10 for each finish line). Fifty measuring locations were chosen randomly along the margin on the dies and the gap width - vertical marginal discrepancy - was measured under a light microscope with a magnification of x100. Measurements were made without cementation. The mean marginal gap widths and standard deviations were calculated and a one-way analysis of variance (ANOVA) was performed for different types of preparations in order to detect differences (alpha = 0.05). RESULTS: The mean marginal gap was 30 +/- 3 MUm for the C group and 28 +/- 4 MUm for the RS group. The one-way ANOVA showed no statistical significant difference between the two groups (P = 0.23). CONCLUSIONS: Within the limitations of this study, the marginal discrepancies were all within the clinical acceptable standard set at 120 MUm. Chamfer and shoulder preparations did not show differences regarding the gap dimension. CLINICAL SIGNIFICANCE: Bur design is an easily selected parameter before natural tooth preparation. Both tested finish lines are able to help clinicians in obtaining acceptable marginal fit values for the investigated zirconia copings. PMID- 25126622 TI - The timing and operational management of the variables of bleaching in cases of rehabilitation in the esthetic field. AB - Managing esthetic restoration in the presence of discolored teeth is a challenge for both the clinical team and clinician, whose aim is to use methods that are as minimally invasive as possible, and materials that allow the preservation of dental tissue. Should one wish to act on the discoloration of teeth that are to be restored, or on adjacent ones, it becomes essential to take action on dental tissues. This is done through bleaching and dental restoration, using materials that allow various clinical situations to be managed, such as those with different tonalities between the teeth: prosthetic materials that offer adequate uniformity in their results in those areas where it is necessary to mask the discoloration. The use of technology such as bleaching, and ceramic materials simultaneously can achieve excellent cosmetic results. This article explains how to integrate bleaching compared to prosthetic treatment, in terms of time, in the various cases of discoloration, and what factors to consider when choosing the timing. PMID- 25126623 TI - Effect of Er,Cr:YSGG laser treatment on microshear bond strength of zirconia to resin cement before and after sintering. AB - PURPOSE: To evaluate the effect of Er,Cr:YSGG laser treatment on microshear bond strength of zirconia to resin cement before and after sintering. MATERIALS AND METHODS: Ninety pre-sintered yttrium-stabilized tetragonal zirconia specimens (4 * 3 * 2 mm) were divided into 6 groups (n = 15). In group C, sintered zirconia was not treated (control group). In groups AS2 and AS3, sintered zirconia blocks were irradiated by Er,Cr:YSGG using a power of 2 and 3 W, respectively. Groups PS2 and PS3 consisted of pre-sintered blocks conditioned by Er,Cr:YSGG at 2 and 3 W, respectively. In group AA, sintered zirconia was air abraded with 50-MUm alumina powder. One block was made using the same preparations as mentioned above and was morphologically assessed by SEM. Microcylinders of Panavia F 2.0 were placed on the treated surface of the groups. Samples were incubated at 37 degrees C and 98% humidity for 48 h and then subjected to microshear bond strength testing. The mode of failure was evaluated. Data were analyzed by one-way ANOVA and Tukey's HSD test (p < 0.05). RESULTS: There was a statistically significant difference between group AA and the others (p < 0.0001). A significant difference was also noted between groups AS3 and C (p = 0.031). Complete surface roughness was seen in group AA and the bond failure was mostly cohesive, while in laser treated groups, the surfaces roughness was much lower vs other groups, and the mode of failure was mostly adhesive. CONCLUSION: Laser treatment of pre-sintered Y-TZP cannot be recommended for improving the bond. Although sandblasting of sintered Y-TZP yielded better results than the rest of the groups, 3 W power after sintering can also be effective in enhancing the bonding strength of resin cement to zirconia. PMID- 25126630 TI - Stage-two surgery using collagen soft tissue grafts: clinical cases and ultrastructural analysis. AB - OBJECTIVE: To present the application of two different soft tissue grafts around dental implants during stage-two surgery. Furthermore, the ultrastructure of these materials is shown and discussed using scanning electron microscopy (SEM). SUMMARY: Although soft tissue autografts may be currently regarded as the gold standard, harvesting of these grafts might lead to higher morbidity, longer chair time, and intra-/postoperative complications at the donor site. New developments in collagen scaff olds have provided an alternative to successfully replace autologous grafts in clinical practice. The SEM pictures clearly show the different composition of a bilayer scaff old (collagen matrix, CM) and a porcine acellular dermal matrix (ADM). These distinctive properties lead to different possible indications. Within the presented cases, ADM was used to augment the ridge contour and was placed into a buccal pouch to achieve complete coverage and an uneventful closed healing. On the other side, CM was left exposed to the oral cavity to successfully gain keratinized mucosa around and between two dental implants. PMID- 25126631 TI - Dental prosthetist experience with oral mucosal screening and referral. AB - OBJECTIVES: This study aimed to investigate dental prosthetists' experiences with screening and referral for suspicious oral mucosal pathology. METHOD AND MATERIALS: Questionnaires regarding oral mucosal screening and referral were mailed to 300 randomly selected dental prosthetists in Australia for selfcompletion. Non-responders were sent replacement questionnaires up to three times, according to the Dillman method. RESULTS: A total of 179 prosthetists returned completed questionnaires resulting in a response rate of 64.9% after excluding 24 due to incorrectly listed addresses. Most participants reported that they checked all new patients for oral mucosal pathology (99.4%) and most reported that they checked all recall patients for mucosal pathology (86%). Most participants had detected a suspicious lesion (86%) and most had referred for a suspicious lesion (77.3%). CONCLUSION: Australian dental prosthetists appear motivated to perform oral mucosal screening and will refer suspicious oral mucosal pathology when detected. PMID- 25126632 TI - A pilot study on spatial changes in the maxilla caused by osteopathic therapy. AB - OBJECTIVES: A variety of theories on the pathogenesis of temporomandibular disorders (TMD) exists resulting in treatment approaches ranging from the fabrication of occlusal splints to alternative treatment modalities such as osteopathy. The goal of this pilot study was to investigate whether osteopathic treatment causes spatial changes in the maxilla. METHOD AND MATERIALS: Following ethics commission approval and informed patient consent, three patients diagnosed with TMD participated in this investigation. In addition to regular treatment, an individualized mandibular occlusal splint was fabricated and a maxillary silicone impression was made. Following osteopathic treatment, the splint was adapted intraorally and another maxillary impression was made. Before and after treatment, the splint and the impressions were scanned three-dimensionally. The resulting images were superimposed using best-fit matching algorithms. RESULTS: Inconsistent spatial changes in the posterior areas were observed both in the maxillary impressions as well as in the mandibular splints reaching maximum absolute values of 0.50 mm. CONCLUSION: Based on this pilot study, it appears that osteopathic treatment may be capable of inducing spatial changes in the maxilla due to sutural movement thereby validating the fundamental principles of osteopathic treatment. Although, based on the study conducted, it cannot be concluded that osteopathy constitutes a successful treatment alternative in TMD patients, practitioners should be aware of this treatment modality. PMID- 25126633 TI - An idiosyncratic post-traumatic tetrad: compound odontome, dentigerous cyst, impaction, and double-dilaceration. AB - OBJECTIVE: This report describes the case of a 13-year-old patient who experienced traumatic intrusion of the primary maxillary right central incisor and subsequently suffered an atypical tetrad, comprising of an unerupted compound odontoma associated with a dentigerous cyst, and an impacted, doubly dilacerated permanent maxillary right central incisor; however, the high interconnectivity of the occurrence of four pathologies together is unusual has not previously been reported. SUMMARY: The pathologies were detected 7 years after trauma; surgical removal of odontome along with the dentigerous cyst was performed, followed by orthodontic extrusion of the impacted double-dilacerated permanent central incisor. The 18-month follow-up shows no pathology, no gingival recession, and normal probing depth. PMID- 25126634 TI - Conservative restorations combined with gingival zenith contour technique. AB - The symmetry, shape, contour, and size of teeth play an important role in the esthetics of the anterior maxillary region of the mouth. However, abnormalities in symmetry and contour can considerably influence the esthetic parameters. Consequently, rehabilitation performed in this region can be challenging and, frequently, multidisciplinary treatment planning that includes esthetics, function, structure, and biologic aspects is paramount. The high demand for esthetic rehabilitations has, therefore, allowed the effective use of minimally invasive techniques to obtain results that mimic natural teeth. This article presents a case report in which both esthetic and functional rehabilitation were obtained by recontouring the gingival zenith followed by placing ultraconservative porcelain veneers. PMID- 25126635 TI - Prosthetic rehabilitation of congenitally missing canines: a case series. AB - Hypodontia is a relatively common finding, although rarely are the canines the missing teeth. Congenitally missing canines are challenging to treat because of their unique role in the masticatory system and the fact that they are in the esthetic zone. This article discusses two patients with missing permanent canines, various treatment planning considerations, and the provided prosthetic solutions. PMID- 25126636 TI - Marginal and internal fit of curved anterior CAD/CAM-milled zirconia fixed dental prostheses: an in-vitro study. AB - OBJECTIVE: To test whether or not different types of CAD/CAM systems, processing zirconia in the densely and in the pre-sintered stage, lead to differences in the accuracy of 4-unit anterior fixed dental prosthesis (FDP) frameworks, and to evaluate the efficiency. METHOD AND MATERIALS: 40 curved anterior 4-unit FDP frameworks were manufactured with four different CAD/CAM systems: DCS Precident (DCS) (control group), Cercon (DeguDent) (test group 1), Cerec InLab (Sirona) (test group 2), Kavo Everest (Kavo) (test group 3). The DCS System was chosen as the control group because the zirconia frameworks are processed in its densely sintered stage and there is no shrinkage of the zirconia during the manufacturing process. The initial fit of the frameworks was checked and adjusted to a subjectively similar level of accuracy by one dental technician, and the time taken for this was recorded. After cementation, the frameworks were embedded into resin and the abutment teeth were cut in mesiodistal and orobuccal directions in four specimens. The thickness of the cement gap was measured at 50* (internal adaptation) and 200* (marginal adaptation) magnification. The measurement of the accuracy was performed at four sites. Site 1: marginal adaptation, the marginal opening at the point of closest perpendicular approximation between the die and framework margin. Site 2: Internal adaptation at the chamfer. Site 3: Internal adaptation at the axial wall. Site 4: Internal adaptation in the occlusal area. The data were analyzed descriptively using the ANOVA and Bonferroni/ Dunn tests. RESULTS: The mean marginal adaptation (site 1) of the control group was 107 +/- 26 MUm; test group 1, 140 +/- 26 MUm; test group 2, 104 +/- 40 MUm; and test group 3, 95 +/- 31 MUm. Test group 1 showed a tendency to exhibit larger marginal gaps than the other groups, however, this difference was only significant when test groups 1 and 3 were compared (P = .0022; Bonferroni/Dunn test). Significantly more time was needed for the adjustment of the frameworks of test group 1 compared to the other test groups and the control group (21.1 min vs 3.8 min) (P < .0001; Bonferroni/Dunn test). For the adjustment of the frameworks of test groups 2 and 3, the same time was needed as for the frameworks of the control group. CONCLUSIONS: No differences of the framework accuracy resulting from the different CAM and CAD/CAM procedures were found; however, only after adjustment of the fit by an experienced dental technician. Hence, the influence of a manual correction of the fit was crucial, and the efforts differed for the tested systems. The CAM system led to lower initial accuracy of the frameworks than the CAD/CAM systems, which may be crucial for the dental laboratory. The stage of the zirconia materials used for the different CAD/CAM procedures, ie presintered or densely sintered, exhibited no influence. PMID- 25126637 TI - Prevalence of peri-implantitis in patients with implant-supported fixed prostheses. AB - OBJECTIVE: The purpose of this study was to evaluate periimplantitis prevalence in patients using implant-supported fixed prostheses that did not have any routine maintenance care. METHOD AND MATERIALS: A total of 161 implants (27 patients) were evaluated in patients using implant-supported fixed prostheses. Collected data included information related to patient general health and local factors such as characteristics of implants, time in function, type of loading, positioning, Modified Bleeding Index, bacterial plaque, bleeding on probing (BOP), marginal recession, probing depth (PD), keratinized mucosa, and radiographic bone loss (BL). Factors related to the prostheses were also evaluated. The exclusion criteria were patients that have had any follow-up visit for plaque control of the prosthesis and/or the implants. RESULTS: From a total of 161 implants, 116 (72%) presented without peri-implantitis (PD > 4 mm + BOP + BL > 2 mm) while 45 (28%) had some sign of the disease. Implants placed in the maxilla were 2.98 times more likely to develop the disease (P < .05). Moreover, patients aged <= 60 years old were 3.24 times more likely to develop peri implantitis (P < .05). Another analysis with statistical relevance (P < .05) was that implants with less than 3 mm interimplant distance were three times more likely to have peri-implantitis. There was no statistical relevance considering other analyses. CONCLUSION: It can be concluded that patients aged <= 60 years have a greater chance of presenting periimplantitis, as well as for implants positioned in the maxilla and those placed with an interimplant distance < 3 mm. PMID- 25126639 TI - Publishing negative results--sometimes it is more important! PMID- 25126638 TI - The sealing ability of ProRoot MTA when placed as an apical barrier using three different techniques: an in-vitro apexification model. AB - OBJECTIVE: To assess the sealing ability of ProRoot MTA when placed as an apical barrier using three different techniques. METHOD AND MATERIALS: Sixty freshly extracted single-rooted human teeth were decoronated and standardized to a root length of 15 mm. The root segments were prepared with Gates Glidden burs to simulate a divergent open apex of immature teeth and randomly assigned into three experimental groups of 20 samples each. MTA (5 mm) was placed by pluggers (Group A), paper points (Group B), or ultrasonic tips (Group C). A cotton pellet moistened with saline was placed in the root canals till the material set, and the coronal portion was sealed with Cavit. After 24 hours, the Cavit and cotton pellet were removed and the canals dried and obturated with warm guttapercha (Obtura) and AH 26 sealer. Coronal portions of all samples were then sealed with Cavit. All root segments were double-coated with nail varnish except for the open apex and were exposed to methylene blue dye for 48 hours at room temperature. The samples were sectioned longitudinally (layer thickness 0.4 mm) and the extent of dye penetration was measured with a stereomicroscope (magnification 20*). RESULTS: The mean depth (+/- standard deviation) of dye leakage for Group A was 1.34 +/- 0.5 mm, Group B 1.25 +/- 0.4 mm, and Group C 1.14 +/- 0.4 mm. There were no significant differences among the three experimental groups (.178 < P < .552). CONCLUSION: ProRoot MTA has a similar sealing ability when placed as an apical barrier with pluggers, paper points, or ultrasonic tips. PMID- 25126640 TI - Longevity of silicate ceramic restorations. AB - The demand for esthetic restorations has resulted in an increased use of dental ceramics as a biocompatible and functionally sufficient alternative to conventional restorative materials. Silicate ceramic restorations are widely used for veneers, inlays, onlays, and crowns in dentistry. Long-term data are of crucial importance to optimize clinical practice. The purpose of the present article is to summarize data of the Innsbruck ceramic evaluation up to 261 months with the focus on longevity and failure characteristics. PMID- 25126641 TI - Geriatric dentistry: new challenges and new opportunities! PMID- 25126642 TI - Criteria for the selection of restoration materials. AB - Selection of the appropriate material for dental restoration has become more and more difficult owing to the increasing variety of restoration materials. A decision flow chart is presented to guide the treatment team (dentist and dental technician) in the selection of the restoration material. This material selection is based on the available interocclusal space, esthetic aspects (eg, brightness value or translucency of the neighboring teeth), as well as clinical evidence extracted from survival rates. PMID- 25126643 TI - Prevalence of periodontal disease in patients with Familial Mediterranean Fever: a cohort study from central Turkey. AB - OBJECTIVE: The aim of this study was to compare the periodontal status in patients with Familial Mediterranean Fever (FMF) and in those without this disease. METHOD AND MATERIALS: 84 subjects clinically diagnosed with FMF and 75 systemically healthy controls, matched by age and gender, were recruited. All FMF patients were on a regular daily colchicine treatment and during attack-free periods. Gingival Index (GI), Plaque Index (PI), probing pocket depth (PD), and clinical attachment level (CAL) were measured in all subjects. To evaluate periodontal disease further, patients were stratified into fi ve groups. Education information and smoking habits were recorded. RESULTS: The FMF patients and healthy controls were comparable for age, gender, and smoking status (P>.05). The FMF patients had significantly higher PI and GI values and lower PD and CAL values than those of the control group (P<.05). However, there was no significant difference among all groups in terms of periodontal disease severity (P>.05). In the FMF-severe periodontitis group, higher PI and GI values were seen (P<.05). However, there was no significant difference between the FMF-severe periodontitis group and the controls with severe periodontitis regarding the PD and CAL values (P>.05). CONCLUSION: Patients with FMF using colchicine did not manifest higher attachment loss compared to age- and sex-matched systemically healthy controls. PMID- 25126644 TI - Full-mouth composite rehabilitation of a mixed erosion and attrition patient: a case report with v-shaped veneers and ultra-thin CAD/CAM composite overlays. AB - Loss of tooth substance has become a common pathology in modern society. It is of multifactorial origin, may be induced by a chemical process or by excessive attrition, and frequently has a combined etiology. Particular care should be taken when diagnosing the cause of dental tissue loss, in order to minimize its impact. Several publications have proposed the use of minimally invasive procedures to treat such patients in preference to traditional full-crown rehabilitation. The use of composite resins, in combination with improvements in dental adhesion, allows a more conservative approach. In this paper, we describe the step-by-step procedure of full-mouth composite rehabilitation with v-shaped veneers and ultra-thin computer-aided design/computer-assisted manufacture (CAD/CAM)- generated composite overlays in a young patient with a combination of erosion and attrition disorder. PMID- 25126645 TI - Immediate postextraction implant with simultaneous buccal plate augmentation, restored with lithium disilicate abutment and veneer: a clinical report. AB - OBJECTIVE: To describe the successful use of biphasic calcium sulfate for improving the buccal plate thickness in an immediate postextraction implant, and its fi nal restoration with custom lithium disilicate abutment and veneer. SUMMARY: A hopeless lateral incisor was replaced with an immediate postextraction implant in conjunction with a buccal plate augmentation based on biphasic calcium sulfate. Satisfactory soft tissue height and quality were maintained following healing. The fi nal restoration managed the severely reduced prosthetic space due to deep bite, and allowed an adhesive luting procedure. PMID- 25126646 TI - Dental implants and osteomyelitis in a patient with osteopetrosis. AB - Osteopetrosis (OP) is a rare genetic metabolic bone disorder characterized by osteoclast dysfunction impairing bone resorption. Together with normal osteoblastic activity this dysfunction promotes intense bone sclerosis with reduction of marrow spaces as well as bone turnover. Maxillofacial complications are common after tooth extraction. Osteomyelitis (OM) of the mandible occurs in around 10% of the cases with OP. The purpose of this paper is to report the fi rst case of OP treated with dental implants, and to describe the protocol used to treat OM that developed after failure of one implant. The treatment of OM included long-term use of antibiotics and marginal bone resection with a piezoelectric device. Similar cases to confirm the efficacy of this treatment are required. PMID- 25126647 TI - Patients perceptions of recovery after maxillary sinus augmentation with a minimally invasive implant device. AB - OBJECTIVE: Patients' perceptions of recovery following sinus augmentation procedures have scarcely been documented. The aim of the present prospective pilot clinical study was to evaluate the patient's perception of immediate postoperative recovery after sinus augmentation, using a minimally invasive implant device. METHOD AND MATERIALS: Eighteen patients (8 men, 10 women), average age 52 (median 48, range 38 to 72), who had been scheduled for sinus augmentation procedures, were asked to enroll in a prospective clinical study. A healthrelated quality-of-life questionnaire was given to the patient. The questionnaire was designed to assess patient's perception of recovery in four main areas: pain, oral function, general activity, and other symptoms. The questionnaire was compared to the surgical chart that described the surgical details and to the outcome. RESULTS: Patients' perceptions of postoperative symptoms in the four tested areas: pain, oral function, general activity, and other symptoms were mostly scored "not at all" or "very little" from postoperative day (POD) 1. Most patients returned to work on POD 1. CONCLUSION: The current results offer a preliminary indication that patients undergoing sinus augmentation using a minimally invasive implant device can expect to experience minimum discomfort and immediate return to everyday activity. PMID- 25126648 TI - A comparison between histologic and clinical diagnoses of oral lesions. AB - OBJECTIVE: The dentist has a fundamental role in the early diagnosis of lesions of the oral cavity. The aim of this study was to establish the rate of erroneous clinical diagnoses and whether a clinical diagnosis is enough. The study was conducted to ascertain the overall accuracy of clinical diagnoses established by dentists. STUDY DESIGN: The biopsy reports of 1,566 samples taken from 1,406 patients and examined at the Dental Outpatients Department of the University of Padua from 1 January 2006 to 30 June 2012 were analyzed in order to compare the presumptive clinical diagnosis with the fi nal diagnosis based on histology. RESULTS: Overall, the dentists' clinical diagnoses were erroneous in 31.5% of cases. These diagnostic errors pertained to 23.8% of the benign neoplasms, 78.9% of the malignant neoplasms, and 17% of precancerous lesions. CONCLUSION: The present report should not be interpreted as a criticism of the clinicians making diagnostic errors but rather a confirmation of the policy to submit excised tissues for histologic examination. PMID- 25126649 TI - Fluorescent sensors for the basic metabolic panel enable measurement with a smart phone device over the physiological range. AB - The advanced functionality of portable devices such as smart phones provides the necessary hardware to potentially perform complex diagnostic measurements in any setting. Recent research and development have utilized cameras and data acquisition properties of smart phones to create diagnostic approaches for a variety of diseases or pollutants. However, in concentration measurements, such as blood glucose, the performance of handheld diagnostic devices depends largely on the sensing mechanism. To expand measurements to multiple components, often necessary in medical tests, with a single diagnostic device, robust platform based sensors are needed. Here, we developed a suite of dual wavelength fluorescent sensors with response characteristics necessary to measure each component of a basic metabolic panel, a common clinical measurement. Furthermore, the response of these sensors could be measured with a simple optical setup to convert a smart phone into a fluorescence measurement instrument. This approach could be used as a mobile basic metabolic panel measurement system for point of care diagnostics. PMID- 25126650 TI - Fluorescence turn-on detection of Sn2+ in live eukaryotic and prokaryotic cells. AB - Sn(2+) is usually added to toothpaste to prevent dental plaque and oral disease. However, studies of its physiological role and bacteriostatic mechanism are restricted by the lack of versatile Sn(2+) detection methods applicable to live cells, including Streptococcus mutans. Here we report two Sn(2+) fluorescent probes containing a rhodamine B derivative as a fluorophore, linked via the amide moiety to N,N-bis(2-hydroxyethyl)ethylenediamine (R1) and tert-butyl carbazate group (R2), respectively. These probes can selectively chelate Sn(2+) and show marked fluorescence enhancement due to the ring open reaction of rhodamine induced by Sn(2+) chelation. The probes have high sensitivity and selectivity for Sn(2+) in the presence of various relevant metal ions. Particularly, both R1 and R2 can target lysosomes, and R2 can probe Sn concentrations in lysosomes with rather acidic microenvironment. Furthermore, these two probes have low toxicity and can be used as imaging probes for monitoring Sn(2+) not only in live KB cells (eukaryotic) but also in Streptococcus mutans cells (prokaryotic), which is a useful tool to study the physiological function of Sn(2+) in biological systems. PMID- 25126651 TI - Alkylation of benzene with carbon monoxide over Zn/H-ZSM-5 zeolite studied using in situ solid-state NMR spectroscopy. AB - Using in situ solid-state NMR spectroscopy we show that CO can act as an alkylating reagent and react with benzene to produce toluene over a Zn/H-ZSM-5 zeolite. In the alkylation reaction, CO provides the methyl group of toluene via a methoxy intermediate. PMID- 25126652 TI - In situ generation of redox active peptides driven by selenoester mediated native chemical ligation. AB - Redox active peptides are generated through selenoester mediated native chemical ligation (NCL). Distinct nanostructures, such as nanotubes to nanofibrillar architectures, were observed for self-assembling soft materials. PMID- 25126653 TI - Zinc-silylene complexes. AB - Reactions of the chlorosilylene [PhC(N(t)Bu)2]SiCl (SiCl) and the aryl and alkyl zincorganyls Zn(C5Me5)2, ZnPh2 and ZnEt2 resulted in the first Zn-silylene complexes. In all reactions the chlorine atom of the silylene and organic groups of the zinc atom are exchanged. By using Zn(C5Me5)2 and ZnPh2 one of the newly formed silylene coordinates to the zinc atom to give [PhC(N(t)Bu)2(eta(1) C5Me5)Si-Zn(eta(2)-C5Me5)Cl] and [PhC(N(t)Bu)2PhSi-ZnPh(MU-Cl)]2, respectively. In contrast, the reaction of SiCl with ZnEt2 resulted due the reduced steric demand of the silylene in the disilylene complex [PhC(N(t)Bu)2SiEt]2ZnCl2, in which both ethyl-moieties are exchanged by chlorides and two newly formed ethyl silylenes coordinate to the zinc atom. PMID- 25126654 TI - Self-healable macro-/microscopic shape memory hydrogels based on supramolecular interactions. AB - A simple strategy is provided to construct novel supramolecular hydrogels with both self-healing and shape memory properties. Starting from achieving self healable hydrogel based on the dynamic interactions of phenylboronic acid modified sodium alginate (Alg-PBA) and poly(vinyl alcohol) (PVA), further formation of a complex of alginate with Ca(2+) renders this hydrogel with the capability of shape memory at the macro-/microscopic scales. PMID- 25126655 TI - Rhodium(II)-catalysed tandem aziridination and ring-opening: stereoselective synthesis of functionalised tetrahydrofurans. AB - Aziridines formed upon treatment of allylic carbamates and homoallylic sulfamates with Rh(II) carboxylate catalysts under oxidative conditions are trapped by suitably-disposed hydroxyl groups to give functionalised tetrahydrofurans. PMID- 25126656 TI - Selective oxidations of activated alcohols in water at room temperature. AB - Allylic and benzylic alcohols can be selectively oxidized to their corresponding aldehydes or ketones in water containing nanoreactors composed of the designer surfactant TPGS-750-M. The oxidation relies on catalytic amounts of CuBr, bpy, and TEMPO, with N-methyl-imidazole; air is the stoichiometric oxidant. PMID- 25126657 TI - Recent progress in the chemistry of endohedral metallofullerenes. AB - Putting metal atoms or metallic clusters into fullerenes has generated a new class of hybrid molecules, defined as endohedral metallofullerenes (EMFs), possessing novel structures and fascinating properties which are different from those of empty fullerenes. In particular, it has been revealed that the chemical properties of the cage carbons of EMFs depend strongly on the nature of the internal metallic species, such as their electronic configuration, location and even motion. Since the first report describing the successful derivatization of La@C82 in 1995, great efforts have been devoted to the chemical modification of EMFs during the last two decades. Although earlier studies mainly focused on readily available species such as M@C82, M2@C80 and M3N@C80 and the related results have been systematically summarized in our previous review paper (Chem. Commun., 2011, 47, 5942-5957), recent concerns about some relatively rare EMFs have developed rapidly. Moreover, taking advantage of single crystal X-ray crystallography, we can now clearly demonstrate the mutual influences between the internal metallic species and the chemical behaviours of the surrounding cage carbons, and the addends as well. In this article, we present recent achievements in the chemical functionalization of EMFs, which were mainly published during the last four years. For consistency, we will still pay special attention to the role that the metals play in controlling the properties of the whole EMF molecules. In this review, however, we will not only focus on concrete experimental results such as X-ray crystallographic and NMR spectroscopic data but will also include computational studies which have indeed enhanced our understanding of the chemical properties of EMFs. Applicable materials based on EMFs are also mentioned but are not discussed in detail. PMID- 25126658 TI - In response. PMID- 25126659 TI - Performance index: An expeditious tool to screen for improved drought resistance in the Lathyrus genus. AB - Some species of the Lathyrus genus are among the most promising crops for marginal lands, with high resilience to drought, flood, and fungal diseases, combined with high yields and seed nutritional value. However, lack of knowledge on the mechanisms underlying its outstanding performance and methodologies to identify elite genotypes has hampered its proper use in breeding. Chlorophyll a fast fluorescence transient (JIP test), was used to evaluate water deficit (WD) resistance in Lathyrus genus. Our results reveal unaltered photochemical values for all studied genotypes showing resistance to mild WD. Under severe WD, two Lathyrus sativus genotypes showed remarkable resilience maintaining the photochemical efficiency, contrary to other genotypes studied. Performance index (PIABS) is the best parameter to screen genotypes with improved performance and grain production under WD. Moreover, we found that JIP indices are good indicators of genotypic grain production under WD. Quantum yield of electron transport (phiEo) and efficiency with which trapped excitons can move electrons further than QA (psi0) revealed as important traits related to improved photosynthetic performance and should be exploited in future Lathyrus germplasm improvements. The JIP test herein described showed to be an expeditious tool to screen and to identify elite genotypes with improved drought resistance. PMID- 25126660 TI - Retraction. Removal notice to "Regional cerebral oxygen saturation on hospital arrival is a potential novel predictor of neurological outcomes at hospital discharge in patients with out-of-hospital cardiac arrest" [Resuscitation 83 (2012) 46-50]. PMID- 25126661 TI - Mental health: Stressed students reach out for help. PMID- 25126663 TI - Local photodynamic therapy delays recurrence of equine periocular squamous cell carcinoma compared to cryotherapy. AB - OBJECTIVE: (i) To report the successful treatment of 10 cases of equine periocular squamous cell carcinoma (PSCC) with surgical excision and photodynamic therapy (PDT) using verteporfin. (ii) To evaluate time to first tumor recurrence between PDT-treated horses and horses treated with surgical excision and cryotherapy. METHODS: A total of 24 equine PSCC cases were included: group 1 (n = 14) had excision and cryotherapy (1993-2003), group 2 (n = 10), excision and local PDT (2006-2010). Evaluated data: signalment, treatment method, tumor location, size, and time to first recurrence. Groups were compared via chi-square test for categorical variables and Wilcoxon rank-sum test for numeric variables. Time to tumor recurrence was examined using Kaplan-Meier product-limit survival analysis. RESULTS: Of 24 cases, nine breeds were affected. Mean age at treatment in years: 14 (range 5-24) in group 1; 11 (range 8-18) in group 2. Median tumor size: 163 mm2 (range 20-625 mm2) in group 1; 195 mm2 (range 45-775 mm2) in group 2. Signalment, tumor laterality, and size were not significantly different between groups. Time to recurrence was significantly different between groups (Logrank test, P = 0.0006). In group 1, 11/14 horses had tumor regrowth with median time to recurrence in months: 10 (range 1-44). In group 2 (minimum follow up of 25 months; range 25-50), no horse demonstrated tumor recurrence after one treatment with excision and PDT. CONCLUSIONS: This represents the first report of local PDT using verteporfin for treatment of equine PSCC. Following surgery, the likelihood of tumor recurrence was significantly reduced with local PDT compared with cryotherapy. PMID- 25126662 TI - Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection. AB - The profile of T-cell receptor beta-chain variable (TRBV) genes usually skews in subjects with virus infection or cancer. The gene melting spectral pattern (GMSP) can be used to determine the profile of the TRBV gene family. To explore the portrait of the TRBV family in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection (AHI), peripheral blood mononuclear cells (PBMCs) were separated and further sorted into CD4+ and CD8+ T cell subsets. The molecular features of the TRBV complementary determining region 3 (CDR3) motifs were determined using GMSP analysis. When aGMSP profile showed a single peak, the monoclonally expanded TRBV gene was cloned and sequenced. Skewed expansions of multiple TRBV genes were observed among the CD4+ and CD8+ T-cell subsets and the PBMCs. The frequency of monoclonally expanded TRBV genes in the CD8+ T-cell subset was significantly higher than that of the CD4+ T-cell subset and the PBMCs. Compared to other members of the TRBV gene family, TRBV11, BV15 and BV20 were predominantly expressed in the repertoire of peripheral blood lymphocytes in recovered AHI subjects. The relatively conserved amino acid motifs of TRBV5.1 and BV20 CDR3 were also detected in the CD4+ and CD8+ T-cell subsets. These results demonstrate the presence of multiple biased TRBV families in recovered AHI subjects. TRBV11, BV15 and BV20, especially from the CD8+ T-cell subset, may be relevant to the pathogenesis of subjects with AHI. The preferentially selected TRBV5.1 and BV20 with the relatively conserved CDR3 motif may be potential targets for personalized treatments of chronic HBV infection. PMID- 25126664 TI - Histopathological features of equine superficial, nonhealing, corneal ulcers. AB - OBJECTIVE: To evaluate corneal changes associated with chronic, nonhealing, superficial, corneal ulcers in horses via common histopathological stains. DESIGN: Retrospective study. ANIMALS: Twenty-four horses diagnosed with chronic, nonhealing, superficial, corneal ulceration. METHODS: The medical records of horses evaluated at North Carolina State University's Veterinary Teaching Hospital (NCSU-VTH) from 2005 to 2011, diagnosed with a chronic, nonhealing, superficial, corneal ulcer and treated with superficial keratectomy (SK) were reviewed. Inclusion criteria were superficial corneal ulceration, no cellular infiltration via slit-lamp biomicroscopy, no microorganisms evident on corneal cytology, and acquisition of samples for aerobic bacterial and common fungal cultures. Corneal tissue samples were evaluated histopathologically for the presence or absence of a nonadherent epithelial 'lip', epithelial dysmaturity, intraepithelial inflammatory cells, an acellular hyaline zone in the anterior stroma, and stromal inflammatory cells, fibrosis and vascularization. RESULTS: In the majority of analyzed samples, epithelial cells adjacent to the ulcerated site showed nonadherence to the basement membrane and dysmaturity. Intraepithelial inflammatory cell infiltration was uncommon. Histopathological features of an anterior stromal hyaline zone, intrastromal inflammation, fibrosis and vascularization were variably present. CONCLUSIONS: The most consistent histopathological characteristics of equine chronic, nonhealing, superficial, corneal ulcers include epithelial nonadherence, epithelial dysmaturity and mild to moderate stromal inflammation; however, one set of histopathological characteristics does not definitively define this syndrome in horses. Additionally, the anterior stromal acellular hyaline zone commonly cited in canine spontaneous chronic corneal epithelial defects (SCCED) is not a consistent finding in equine corneas. PMID- 25126665 TI - Suberoylanilide hydroxamic acid (vorinostat): its role on equine corneal fibrosis and matrix metalloproteinase activity. AB - OBJECTIVE: To explore the effect of suberoylanilide hydroxamic acid (SAHA) (i) on corneal fibroblast differentiation, morphology, and viability; and (ii) on the expression levels of matrix metalloproteinases (MMPs) 2 and 9 using an in vitro model of equine corneal fibrosis. PROCEDURE: Healthy donor corneas were used to generate primary cultures of equine corneal fibroblasts. The fibroblasts were exposed to 5 ng/mL TGFbeta1 to induce myofibroblast formation. The cultures were treated with either 5 MUm or 10 MUm SAHA for 72 h in the presence of TGFbeta1. Real-time PCR and immunocytochemistry were used to determine the antifibrotic efficacy of SAHA by quantifying alpha-smooth muscle actin (alphaSMA), a marker of myofibroblast formation and fibrosis. Real-time PCR was used to determine the effects of SAHA on MMP2 and MMP9 expression. Cytotoxicity of SAHA was evaluated with phase contrast microscopy and trypan blue exclusion assays. RESULTS: Suberoylanilide hydroxamic acid (SAHA) significantly attenuated TGFbeta1-induced differentiation of equine fibroblasts to myofibroblasts as indicated by 3- to 3.5 fold (P < 0.001) decrease in alphaSMA mRNA and 86-88% (P < 0.001) decrease in alphaSMA+ immunocytochemical staining. SAHA treatment also resulted in 4.5- to 5.5-fold (P < 0.01) decrease in MMP9 expression. A dose-dependent bimodal effect of SAHA on MMP2 expression was noted (3.5-fold increase with 5 MUm dose; 0.5-fold decrease with 10 MUm dose). No change in fibroblast viability was observed with a 5 MUm SAHA dose, whereas a 10 MUm dose resulted in a moderate 17% decrease in cell viability. CONCLUSIONS: Suberoylanilide hydroxamic acid (SAHA) can effectively inhibit TGFbeta-induced differentiation of equine corneal fibroblasts to myofibroblasts and modulates MMP production in vitro. PMID- 25126666 TI - Gold-thiolate ring as a protecting motif in the Au20(SR)16 nanocluster and implications. AB - Understanding how gold nanoclusters nucleate from Au(I)SR complexes necessitates the structural elucidation of nanoclusters with decreasing size. Toward this effort, we herein report the crystal structure of an ultrasmall nanocluster formulated as Au20(TBBT)16 (TBBT = SPh-t-Bu). The structure features a vertex sharing bitetrahedral Au7 kernel and an unprecedented "ring" motif-Au8(SR)8. This large ring protects the Au7 kernel through strong Auring-Aukernel bonding but does not involve S-Aukernel bonding, in contrast to the common "staple" motifs in which the S-Aukernel bonding is dominant but the Austaple-Aukernel interaction is weak (i.e., aurophilic). As the smallest member in the TBBT "magic series", Au20(TBBT)16, together with Au28(TBBT)20, Au36(TBBT)24, and Au44(TBBT)28, reveals remarkable size-growth patterns in both geometric structure and electronic nature. Moreover, Au20(TBBT)16, together with the Au24(SR)20 and Au18(SR)14 nanoclusters, forms a "4e" nanocluster family, which illustrates a trend of shrinkage of bitetrahedral kernels from Au8(4+) to Au7(3+) and possibly to Au6(2+) with decreasing size. PMID- 25126667 TI - Bioelectronic tongue using heterodimeric human taste receptor for the discrimination of sweeteners with human-like performance. AB - The sense of taste helps humans to obtain information and form a picture of the world by recognizing chemicals in their environments. Over the past decade, large advances have been made in understanding the mechanisms of taste detection and mimicking its capability using artificial sensor devices. However, the detection capability of previous artificial taste sensors has been far inferior to that of animal tongues, in terms of its sensitivity and selectivity. Herein, we developed a bioelectronic tongue using heterodimeric human sweet taste receptors for the detection and discrimination of sweeteners with human-like performance, where single-walled carbon nanotube field-effect transistors were functionalized with nanovesicles containing human sweet taste receptors and used to detect the binding of sweeteners to the taste receptors. The receptors are heterodimeric G protein-coupled receptors (GPCRs) composed of human taste receptor type 1 member 2 (hTAS1R2) and human taste receptor type 1 member 3 (hTAS1R3), which have multiple binding sites and allow a human tongue-like broad selectivity for the detection of sweeteners. This nanovesicle-based bioelectronic tongue can be a powerful tool for the detection of sweeteners as an alternative to labor intensive and time-consuming cell-based assays and the sensory evaluation panels used in the food and beverage industry. Furthermore, this study also allows the artificial sensor to exam the functional activity of dimeric GPCRs. PMID- 25126670 TI - Chemistry makes graphene beyond graphene. AB - Although graphene is extremely inert in chemistry because of the giant delocalized pi electron system, various methods have been developed to achieve its efficient chemical modification. Covalent chemistry is effective to modulate the physical properties of graphene. By converting the sp(2) hybridized carbon atoms to sp(3) ones, new two-dimensional (2D) materials and 2D superlattices with fascinating features beyond mother graphene could be built from the graphene scaffold, greatly expanding the graphene family and its attraction. In this Perspective, the power of covalent chemistry is demonstrated from the viewpoint of tailoring graphene's energy band structure as well as creating new 2D materials and 2D superlattices. A specific focus is laid on the general consideration and understanding of covalent graphene chemistry toward electronic devices and material science. PMID- 25126671 TI - Manganese nanoparticles: impact on non-nodulated plant as a potent enhancer in nitrogen metabolism and toxicity study both in vivo and in vitro. AB - Mung bean plants were grown under controlled conditions and supplemented with macro- and micronutrients. The objective of this study was to determine the response of manganese nanoparticles (MnNP) in nitrate uptake, assimilation, and metabolism compared with the commercially used manganese salt, manganese sulfate (MS). MnNP was modulated to affect the assimilatory process by enhancing the net flux of nitrogen assimilation through NR-NiR and GS-GOGAT pathways. This study was associated with toxicological investigation on in vitro and in vivo systems to promote MnNP as nanofertilizer and can be used as an alternative to MS. MnNP did not impart any toxicity to the mice brain mitochondria except in the partial inhibition of complex II-III activity in ETC. Therefore, mitochondrial dysfunction and neurotoxicity, which were noted by excess usage of elemental manganese, were prevented. This is the first attempt to highlight the nitrogen uptake, assimilation, and metabolism in a plant system using a nanoparticle to promote a biosafe nanomicronutrient-based crop management. PMID- 25126672 TI - L1 cell adhesion molecule is a strong predictor for distant recurrence and overall survival in early stage endometrial cancer: pooled PORTEC trial results. AB - BACKGROUND: L1 cell adhesion molecule (L1CAM) expression has been implicated as risk factor for disease recurrence in endometrial cancer (EC), most likely due to its role in promoting tumour cell motility. We tested the performance of L1CAM expression in predicting the risk of recurrence in the randomised post operative radiation therapy in endometrial carcinoma (PORTEC)-1 and -2 trials. METHODS: In the PORTEC trials, stage I EC patients were randomised to external beam radiotherapy (EBRT) versus no additional treatment (PORTEC-1, n=714), or to EBRT versus vaginal brachytherapy (PORTEC-2, n=427). Tumour samples of 865 (75.8%) patients were available for L1CAM expression analysis by immunohistochemistry. An established scoring system for EC was used, with >10% L1CAM staining defined as positive. RESULTS: Positive L1CAM expression was significantly correlated with risk of distant recurrence, with a hazard ratio (HR) of 5.1 (95% confidence interval (CI) 3.1-8.7) but not with vaginal relapse, while a trend for pelvic nodal relapse was found. Tumours with the highest expression levels (>50% positive) had the strongest risk of distant recurrence (HR 5.3, CI 2.7-10.4). In multivariate Cox analysis with the risk factors age, depth of invasion, grade, lympho-vascular space invasion (LVSI) and treatment, L1CAM expression remained an independent prognostic factor for distant recurrence (HR 3.5, CI 1.92-6.30) and overall survival (HR 2.1, CI 1.41-2.98). CONCLUSION: L1CAM expression is a strong independent predictor for distant recurrence and overall survival in stage I endometrial cancer. These results warrant prospective validation of L1CAM as marker for selecting patients who could benefit from more extensive diagnostic and/or therapeutic procedures. PMID- 25126673 TI - Enantioselective synthesis of the predominant AB ring system of the Schisandra nortriterpenoid natural products. AB - An enantioselective synthesis of the AB ring system common to the majority of the Schisandra nortriterpenoid natural products is reported. Key steps include a stereospecific ring opening of a trisubstituted epoxide and the use of a beta lactone to enable installation of the gem-dimethyl functionality of the B ring. An acetalization strategy played a key role in a late-stage biomimetic AB ring bicyclization. PMID- 25126676 TI - Complementarity of EIS and SPR to reveal specific and nonspecific binding when interrogating a model bioaffinity sensor; perspective offered by plasmonic based EIS. AB - The present work compares the responses of a model bioaffinity sensor based on a dielectric functionalization layer, in terms of specific and nonspecific binding, when interrogated simultaneously by Surface Plasmon Resonance (SPR), non-Faradaic Electrochemical Impedance Spectroscopy (EIS), and Plasmonic based-EIS (P-EIS). While biorecognition events triggered a sensitive SPR signal, the related EIS response was rather negligible. Contrarily, even a limited nonspecific adsorption onto the surface of the metallic electrode, allowed by the intrinsic imperfect compactness of the functionalization layers, was signaled by EIS and not by SPR. The source of this finding has been addressed from both theoretical and experimental perspectives, demonstrating that EIS signals are mainly sensitive to adsorptions that alter the current pathway through defects of the functionalization layer exposing the electrode. These observations are of importance for those developing biosensors analyzed by SPR, EIS, or the novel combination of the two methods (P-EIS). A possible application of the observed complementarity of the two methods, namely assessment of sample purity in respect to a target analyte is highlighted. Moreover, the possibility of false-positive EIS responses (determined by nonspecific binding) when assessing samples containing complex matrices or consisting of small molecular weight analytes is emphasized. PMID- 25126675 TI - Camouflage effects following resin infiltration of postorthodontic white-spot lesions in vivo: One-year follow-up. AB - OBJECTIVE: To assess camouflage effects by concealment of postorthodontic white spot lesions (WSLs) to sound adjacent enamel (SAE) achieved over 12 months with resin infiltration (Icon, DMG, Hamburg, Germany). METHODS: Twenty subjects (trial teeth nteeth = 111) who had received resin infiltration treatment of noncavitated postorthodontic WSLs were contacted for a 1-year follow-up assessment of CIE L*a*b* colors (T12). Color and lightness (CIE-L*a*b*) data for WSLs and SAE were compared to baseline data assessed before infiltration (T0) and those assessed after 6 months (T6), using a spectrophotometer. The target parameter was the difference between the summarized color and lightness values (DeltaEWSL/SAE). Intergroup (WSL, SAE) and intertime comparisons (T0 vs T6, T12) were performed using paired t-tests at a significance level of alpha = 5%. RESULTS: Nine subjects (trial teeth nteeth = 49; male/female ratio 5/4; age range 13-19 years) were available at T12. After the highly significant reduction of DeltaEWSL/SAE discrepancies between T0 and T6, analysis of 12-month records revealed color and lightness discrepancy of WSL vs SAE that was significantly decreased compared with baseline, indicating an assimilation of WSL color to SAE appearance after infiltration, while an additional reduction of discrepancies between T6 and T12 was not significant. CONCLUSION: As color and lightness characteristics of the Icon infiltrant as well as the esthetic camouflage effects achieved by WSL infiltration were not altered significantly or clinically relevant after 12 months, the method of resin infiltration can be recommended for an enduring esthetic improvement of postorthodontic WSL. PMID- 25126677 TI - James F. Jerger, PhD, responds to five questions. PMID- 25126674 TI - Atypical cell populations associated with acquired resistance to cytostatics and cancer stem cell features: the role of mitochondria in nuclear encapsulation. AB - Until recently, acquired resistance to cytostatics had mostly been attributed to biochemical mechanisms such as decreased intake and/or increased efflux of therapeutics, enhanced DNA repair, and altered activity or deregulation of target proteins. Although these mechanisms have been widely investigated, little is known about membrane barriers responsible for the chemical imperviousness of cell compartments and cellular segregation in cytostatic-treated tumors. In highly heterogeneous cross-resistant and radiorefractory cell populations selected by exposure to anticancer agents, we found a number of atypical recurrent cell types in (1) tumor cell cultures of different embryonic origins, (2) mouse xenografts, and (3) paraffin sections from patient tumors. Alongside morphologic peculiarities, these populations presented cancer stem cell markers, aberrant signaling pathways, and a set of deregulated miRNAs known to confer both stem cell phenotypes and highly aggressive tumor behavior. The first type, named spiral cells, is marked by a spiral arrangement of nuclei. The second type, monastery cells, is characterized by prominent walls inside which daughter cells can be seen maturing amid a rich mitochondrial environment. The third type, called pregnant cells, is a giant cell with a syncytium-like morphology, a main nucleus, and many endoreplicative functional progeny cells. A rare fourth cell type identified in leukemia was christened shepherd cells, as it was always associated with clusters of smaller cells. Furthermore, a portion of resistant tumor cells displayed nuclear encapsulation via mitochondrial aggregation in the nuclear perimeter in response to cytostatic insults, probably conferring imperviousness to drugs and long periods of dormancy until nuclear eclosion takes place. This phenomenon was correlated with an increase in both intracellular and intercellular mitochondrial traffic as well as with the uptake of free extracellular mitochondria. All these cellular disorders could, in fact, be found in untreated tumor cells but were more pronounced in resistant entities, suggesting a natural mechanism of cell survival triggered by chemical injury, or a primitive strategy to ensure stemming, self-renewal, and differentiation under adverse conditions, a fact that may play a significant role in chemotherapy outcomes. PMID- 25126679 TI - Aural rehabilitation through music workshops for cochlear implant users. AB - BACKGROUND: It has been reported that after speech perception, music appreciation is the second most commonly expressed requirement among cochlear implant (CI) recipients. Certain features of music are known to be more readily accessible; however, provision of music rehabilitation for adult CI users is limited. PURPOSE: A series of music workshops were organized to (1) enable attendees to explore which aspects of music they are able to perceive and appreciate; (2) raise awareness of listening strategies, technology, and rehabilitation resources for music; and (3) develop ideas, and prototype software, for inclusion in a music rehabilitation program. The therapeutic value of music workshops was concurrently investigated. RESEARCH DESIGN: A qualitative, longitudinal study was used. Two consultation meetings were held before a series of nine music workshops that occurred over a period of 5 mo. STUDY SAMPLE: Five adult CI users participated in consultations before the workshops. Twenty-eight adult CI users from the South of England Cochlear Implant Centre attended at least one of the workshops. INTERVENTION: Participants could attend as many workshops as they wished. Each workshop lasted between 2 to 2.5 hr and included individual computer based and group activities. DATA COLLECTION AND ANALYSIS: Responses to open-ended questions were transcribed in the consultation meetings and used to develop workshop activities. A preworkshop survey was used to determine attendees' aspirations and expectations. Postworkshop surveys were used to qualitatively and quantitatively evaluate attendees' immediate reactions to the workshop content, software, and perceived benefits. A 2-month, postworkshop survey evaluated the longer-term impact of the workshops. RESULTS: Overall reaction to the workshops and prototype software was positive. All attendees indicated that they anticipated changing how they engaged with music as a result of the workshops, and data from the preworkshop and postworkshop surveys suggest a positive change in listening habits. CONCLUSIONS: The workshops proved to be an effective means of simultaneously encouraging music exploration in a social and safe environment and obtaining feedback on prototype rehabilitation materials. Survey data suggested that through group listening and practical activities, certain aspects of music can be accessible and rewarding through a CI, leading to positive changes in attitude and behavior toward music. PMID- 25126680 TI - The influence of aging on interaural asymmetries in middle latency response amplitude. AB - BACKGROUND: Auditory-evoked potentials (EPs) provide a more objective assessment of central auditory nervous system (CANS) dysfunction when compared to behavioral measures because they do not require a behavioral response (Anderson and Kraus, 2010). In this regard, the middle latency response (MLR) has been considered an important component of CANS assessment (Jerger et al, 1988); however, its large within-group variability limits its usefulness (Musiek et al, 1999). It has been argued that performing intratest calculations on the MLR (e.g., difference in EP amplitude when stimulating the left ear versus the right ear) can reduce the within-group variability of the MLR and enhance its clinical usefulness (Musiek et al, 1999; Weihing et al, 2012). To date, it has not been investigated how well these MLR intratest measures reduce within-group variability in adults of various ages, nor has it been shown that these intratest measures are sensitive to aging related changes in the CANS. PURPOSE: The two primary goals of the present study were (1) to determine if calculating an intratest MLR measure, the difference in MLR Na-Pa peak-to-peak amplitude on left versus right ear stimulation (i.e., "ear effects"), will reduce within-group variability in adults of various ages; and (2) to determine if ear effect magnitude will change as a function of aging. Ear effects were measured in both quiet and in noise to determine if the addition of noise enhanced any age-related-effects. RESEARCH DESIGN: A cross-sectional study was conducted. STUDY SAMPLE: The researchers studied 30 adults ranging in age from 20-80 yr with hearing sensitivity of 25 dB HL or better at the octave frequencies from 500-2000 Hz, and no history of neurologic issues. Adults were assigned to one of three age groups based on their chronological age, which were young adults, middle-aged adults, and older adults. DATA COLLECTION AND ANALYSIS: MLRs were acquired using a Nicolet Spirit 2000 during a single laboratory visit. To determine if within-group variability decreased significantly with ear effects, variability for absolute amplitude measures was compared to ear effect variability using the Pitman t-test. To examine potential effects of background noise and aging, data were analyzed using a mixed-factorial analysis of variance with the within-subjects factor "background noise" and the between-subjects factor "age group." RESULTS: Within-group variability was significantly reduced by calculating ear effects for the youngest group only. Additionally, the oldest adults in the present sample showed significantly larger ear effects than younger and middle-aged adults. This effect did not appear to be a result of differences in peripheral hearing sensitivity. Finally, introducing noise into the paradigm did not influence the observed effects. CONCLUSIONS: Ear effects become larger in older adults possibly as a result of age-related changes in the subcortical and/or cortical generators of the MLR. Failure of the ear effect calculation to reduce within-group variability in the middle-aged and older adults suggests that interaural asymmetries in MLR amplitude become more variable across participants who are older than 50 yr. Information obtained from this measure may benefit the development of treatment plans for older adults with hearing difficulties. PMID- 25126681 TI - Music therapy for chronic tinnitus: variability of tinnitus pitch in the course of therapy. AB - BACKGROUND: In general, tinnitus pitch has been observed to be variable across time for most patients experiencing tinnitus. Some tinnitus therapies relate to the dominant tinnitus pitch in order to adjust therapeutic interventions. As studies focusing on tinnitus pitch rarely conduct consecutive pitch matching in therapeutic settings, little is known about the course and variability of tinnitus pitch during therapeutic interventions. PURPOSE: The purpose of this study was to investigate the variability and development of tinnitus pitch in the course of therapeutic interventions. Tinnitus pitch was suspected to be highly variable. RESEARCH DESIGN: The researchers conducted a descriptive, retrospective analysis of data. STUDY SAMPLE: A total of 175 adult patients experiencing chronic tinnitus served as participants. All patients had received a neuro-music therapy according to the "Heidelberg Model of Music Therapy for Chronic Tinnitus." DATA COLLECTION AND ANALYSIS: During therapeutic interventions lasting for 5 consecutive days, the individual tinnitus frequency was assessed daily by means of a tinnitus pitch-matching procedure. The extent of variability in tinnitus pitch was calculated by mean ratios of frequencies between subsequent tinnitus measurements. Analysis of variance of repeated measures and post hoc paired samples t-tests were used for comparison of means in tinnitus frequencies, and the test-retest reliability of measurements was obtained by the Pearson product-moment correlation coefficient. RESULTS: Tinnitus pitch displayed a variability of approximately 3/5 to 4/5 octaves per day. Overall, the mean frequency declined in the course of the therapy. Detailed analysis revealed three groups of patients with diverging tinnitus progression. The test-retest reliability between assessments turned out to be robust (r = 0.74 or higher). CONCLUSIONS: Considerable variation in tinnitus pitch was found. Consequently, a frequent rechecking of tinnitus frequency is suggested during frequency-specific acoustic stimulation in order to train appropriate frequency bands. PMID- 25126682 TI - Normative sweep frequency impedance measures in healthy neonates. AB - BACKGROUND: Diagnosing middle ear disorders in neonates is a challenging task for both audiologists and otolaryngologists. Although high-frequency (1000 Hz) tympanometry and acoustic stapedial reflex tests are useful in diagnosing middle ear problems in this age group, they do not provide information about the dynamics of the middle ear in terms of its resonance frequency (RF) and mobility. The sweep frequency impedance (SFI) test can provide this information, which may assist in the diagnosis of middle ear dysfunction in neonates. PURPOSE: This study aimed to investigate the feasibility of testing neonates using the SFI technique, establish normative SFI data for RF and mobility of the middle ear in terms of changes in sound pressure level (?SPL in dB), and describe the dynamics of the middle ear in healthy Australian neonates. STUDY SAMPLE: A prospective sample of 100 neonates (58 males, 42 females) with a mean gestational age of 39.3 wk (SD = 1.3 wk; range = 38-42 wk), who passed all three tests, namely, automated auditory brainstem response, transient evoked otoacoustic emissions, and 1000 Hz tympanometry, were included in this study. DATA COLLECTION AND ANALYSIS: A SFI research prototype was used to collect the data. First, the SPL in the ear canal was measured as a probe-tone frequency was swept from 100-2000 Hz with the ear canal static pressure held constant at 200 daPa. Then, this measurement was repeated with the static pressure reduced in 50 daPa steps to -200 daPa. Additional measurement was also performed at the static pressure, where the peak of the 1000 Hz tympanogram occurred. A graph showing the variation of SPL against frequency at all static pressures was plotted. From this graph, the RF and ?SPL at tympanometric peak pressure (TPP) were determined. Descriptive statistics and an analysis of variance (ANOVA) were applied to the RF and ?SPL data with gender and ear as independent variables. RESULTS: The results showed two resonance regions of the outer/middle ear with the high RF (mean = 1236 Hz; 90% range: 830 1518 Hz) being approximately equal to four times that of the low RF (mean = 287 Hz; 90% range = 209-420 Hz). The low RF was more easily identifiable than the high RF. The ?SPL at the low RF (mean = 8.2 dB; 90% range = 3.4-13 dB) was greater than that at the high RF (mean = 5.0 dB; 90% range = 1.5-8.1 dB). There were no significant differences or interactions between genders and ears. CONCLUSION: The study showed that the SFI is a feasible test of middle ear function in neonates. The SFI results revealed two regions of resonance with the lower resonance (287 Hz) possibly related to the movements of the outer ear canal wall and higher resonance (1236 Hz) related to the resonance of the middle ear. The normative data developed in this study will be useful in evaluating outer and middle ear function in neonates. PMID- 25126683 TI - Speech-on-speech masking with variable access to the linguistic content of the masker speech for native and nonnative english speakers. AB - BACKGROUND: Masking release for an English sentence-recognition task in the presence of foreign-accented English speech compared with native-accented English speech was reported in Calandruccio et al (2010a). The masking release appeared to increase as the masker intelligibility decreased. However, it could not be ruled out that spectral differences between the speech maskers were influencing the significant differences observed. PURPOSE: The purpose of the current experiment was to minimize spectral differences between speech maskers to determine how various amounts of linguistic information within competing speech Affiliationect masking release. RESEARCH DESIGN: A mixed-model design with within subject (four two-talker speech maskers) and between-subject (listener group) factors was conducted. Speech maskers included native-accented English speech and high-intelligibility, moderate-intelligibility, and low-intelligibility Mandarin accented English. Normalizing the long-term average speech spectra of the maskers to each other minimized spectral differences between the masker conditions. STUDY SAMPLE: Three listener groups were tested, including monolingual English speakers with normal hearing, nonnative English speakers with normal hearing, and monolingual English speakers with hearing loss. The nonnative English speakers were from various native language backgrounds, not including Mandarin (or any other Chinese dialect). Listeners with hearing loss had symmetric mild sloping to moderate sensorineural hearing loss. DATA COLLECTION AND ANALYSIS: Listeners were asked to repeat back sentences that were presented in the presence of four different two-talker speech maskers. Responses were scored based on the key words within the sentences (100 key words per masker condition). A mixed-model regression analysis was used to analyze the difference in performance scores between the masker conditions and listener groups. RESULTS: Monolingual English speakers with normal hearing benefited when the competing speech signal was foreign accented compared with native accented, allowing for improved speech recognition. Various levels of intelligibility across the foreign-accented speech maskers did not influence results. Neither the nonnative English-speaking listeners with normal hearing nor the monolingual English speakers with hearing loss benefited from masking release when the masker was changed from native accented to foreign-accented English. CONCLUSIONS: Slight modifications between the target and the masker speech allowed monolingual English speakers with normal hearing to improve their recognition of native-accented English, even when the competing speech was highly intelligible. Further research is needed to determine which modifications within the competing speech signal caused the Mandarin accented English to be less effective with respect to masking. Determining the influences within the competing speech that make it less effective as a masker or determining why monolingual normal-hearing listeners can take advantage of these differences could help improve speech recognition for those with hearing loss in the future. PMID- 25126685 TI - Pediatric hearing aid use: how can audiologists support parents to increase consistency? AB - BACKGROUND: Children need consistent access to the full range of speech sounds for spoken language development, making daily hearing aid management a fundamental component of effective intervention. In addition to receiving services from professionals with expertise in childhood hearing loss, parents play a central role in the intervention process. However, parents can experience an array of barriers and challenges in learning to cope with the demands of daily management. Feedback about hearing aid use time might offer parents insight into challenges and lead to the identification of strategies to increase use, optimizing child outcomes. PURPOSE: This exploratory study had 2 primary purposes: (1) to examine hearing aid use time for a cohort of children 7 mo to 6 yr of age and (2) to examine whether hearing aid use time increased when parents were given periodic objective feedback (i.e., data-logging results) about average daily use time. RESEARCH DESIGN: A retrospective chart review was used to collect data on eligible participants. RESULTS: Findings for 29 children (7 mo to 6 yr of age) revealed variability in hours of hearing aid use and an increase in hours of use with age and severity of hearing loss. Reports of typical hearing aid use from seven parents revealed that parents overestimated use by an average of 3.36 hr. Review of challenges reported revealed issues with retention, awareness of the effect of nonuse on average daily access to sound, and lack of perceived benefit of hearing aid use. Hearing aid use increased with communication about data logging for some, but not all, parents. CONCLUSIONS: For effective integration of essential hearing aid management skills into the daily lives of primary caregivers, audiologists must consider caregiver needs in the overall child management and monitoring plan. The ability to optimize child outcomes might depend in part on the extent audiologists embrace family-centered services, engage in collaborative problem solving, and support parents in applying individualized strategies. PMID- 25126684 TI - Effect of different signal-processing options on speech-in-noise recognition for cochlear implant recipients with the cochlear CP810 speech processor. AB - BACKGROUND: Difficulty understanding speech in the presence of background noise is a common report among cochlear implant (CI) recipients. Several speech processing options designed to improve speech recognition, especially in noise, are currently available in the Cochlear Nucleus CP810 speech processor. These include adaptive dynamic range optimization (ADRO), autosensitivity control (ASC), Beam, and Zoom. PURPOSE: The purpose of this study was to evaluate CI recipients' speech-in-noise recognition to determine which currently available processing option or options resulted in best performance in a simulated restaurant environment. RESEARCH DESIGN: Experimental study with one study group. The independent variable was speech-processing option, and the dependent variable was the reception threshold for sentences score. STUDY SAMPLE: Thirty-two adult CI recipients. INTERVENTION: Eight processing options were tested: Beam, Beam + ASC, Beam + ADRO, Beam + ASC + ADRO, Zoom, Zoom + ASC, Zoom + ADRO, and Zoom + ASC + ADRO. DATA COLLECTION AND ANALYSIS: Participants repeated Hearing in Noise Test sentences presented at a 0 degrees azimuth, with R-Space restaurant noise presented from a 360 degrees eight-loudspeaker array at 70 dB sound pressure level. A one-way repeated-measures analysis of variance was used to analyze differences in Beam options, Zoom options, and Beam versus Zoom options. RESULTS: Among the Beam options, Beam + ADRO was significantly poorer than Beam only, Beam + ASC, and Beam + ASC + ADRO. A 1.6-dB difference was observed between the best (Beam only) and poorest (Beam + ADRO) options. Among the Zoom options, Zoom only and Zoom + ADRO were significantly poorer than Zoom + ASC. A 2.2-dB difference was observed between the best (Zoom + ASC) and poorest (Zoom only) options. The comparison between Beam and Zoom options showed one significant difference, with Zoom only significantly poorer than Beam only. No significant difference was found between the other Beam and Zoom options (Beam + ASC vs Zoom + ASC, Beam + ADRO vs Zoom + ADRO, and Beam + ASC + ADRO vs Zoom + ASC + ADRO). The best processing option varied across subjects, with an almost equal number of participants performing best with a Beam option (n = 15) compared with a Zoom option (n = 17). There were no significant demographic or audiological moderating variables for any option. CONCLUSIONS: The results showed no significant differences between adaptive directionality (Beam) and fixed directionality (Zoom) when ASC was active in the R-Space environment. This finding suggests that noise-reduction processing is extremely valuable in loud semidiffuse environments in which the effectiveness of directional filtering might be diminished. However, there was no significant difference between the Beam-only and Beam + ASC options, which is most likely related to the additional noise cancellation performed by the Beam option (i.e., two-stage directional filtering and noise cancellation). In addition, the processing options with ADRO resulted in the poorest performances. This could be related to how the CI recipients were programmed or the loud noise level used in this study. The best processing option varied across subjects, but the majority performed best with directional filtering (Beam or Zoom) in combination with ASC. Therefore in a loud semidiffuse environment, the use of either Beam + ASC or Zoom + ASC is recommended. PMID- 25126686 TI - Survey of audiologists' views on risk of falling assessment in the clinic. AB - BACKGROUND: Falls are a significant health problem for older adults. With the projected increase in persons aged 65 yr and older by the year 2050, this continues to be a growing concern. Risk of falling (RoF) assessment is a multifactorial approach. Audiologists routinely evaluate older patients in the clinic and therefore might be in an ideal position to identify falling risk factors. PURPOSE: The purpose of this study was to gain a better understanding of audiologists' views on RoF assessment related to training and education, screening and assessment, prevention and intervention, the effectiveness of RoF assessment, and challenges associated with RoF assessment in the audiology clinic. RESEARCH DESIGN: The survey was e-mailed to 2000 randomly selected audiologists across the United States. The survey was designed with the primary objective of understanding personal views regarding RoF assessment. Demographic information was included to better understand the type of clinic setting, the primary age of patients, year of graduation, and highest degree earned. Additionally, open-ended questions were offered to provide a forum for further testimonials on current RoF experiences and needs. Questions pertaining to resources used to assess RoF and counsel patients on RoF were asked to determine the audiologists' understanding of a multifactorial approach to assessing patients for RoF. Lastly, a series of Likert scale questions were developed to indicate the strength of agreement or disagreement pertaining to general statements about RoF assessment and the challenges associated with an RoF assessment program. Descriptive statistics (means, standard deviations, frequencies, and percentages) were used for quantitative survey responses. Validation of qualitative data was completed by using triangulation sources. RESULTS: A total of 275 of 2000 audiologists returned the survey; of those who responded, 238 audiologists were analyzed. Two themes emerged from the survey responses: resources used to assess RoF and audiologists' personal views on RoF. Although a majority (83.0% [n = 197/238]) of audiologists surveyed indicated working with geriatric patients (>=61 yr of age), more than half (62.1% [n = 147/238]) of audiologists surveyed indicated no experience with RoF assessment. Overall, 75% (n = 175/233) of the surveyed audiologists consider RoF assessment a role in the audiologist's scope of practice; however, only 16.3% (n = 38/233) believe audiologists are knowledgeable, 11.8% (n = 27/228) believe audiologists are sufficiently trained to provide RoF assessment, and 14% (n = 33/238) are currently implementing RoF as part of vestibular and balance assessment. CONCLUSIONS: Although audiologists support RoF assessment, further education is warranted for audiologists to efficiently assess RoF. Many audiologists do not have the resources or time to administer RoF assessment in their clinics; however, if audiologists can ask just a few questions regarding fall history and better understand the risk factors, they can be in a position to refer their patients to other professionals for further investigation. PMID- 25126687 TI - Overview of nine computerized, home-based auditory-training programs for adult cochlear implant recipients. AB - BACKGROUND: Computerized, home-based auditory-training programs could be attractive to cochlear implant (CI) recipients who cannot obtain direct intensive training services and also to busy clinicians who would like to enable CI recipients to benefit from these programs. However, it is difficult for either group to know which of the many programs available might best suit individual needs. PURPOSE: Selecting a computerized home-based program can be challenging because each offers different features. This article provides an overview of currently available programs to help clinicians and recipients choose one that is most suitable. DATA COLLECTION AND ANALYSIS: A narrative literature review and an advanced Google search of Web sites linked to auditory-training programs were conducted. This overview builds on and updates information from previous literature. RESULTS: Nine computerized, home-based auditory-training programs were identified for overview. Twenty-nine information items and features for each of the nine programs are presented, categorized by general product and purchase information, design features of the training paradigm, and auditory and communication targets. CONCLUSIONS: This article provides a descriptive overview of computerized, home-based auditory-training programs for the use of clinicians, CI recipients, researchers, and hearing aid users. PMID- 25126688 TI - Comment regarding Hannula et al, 2011. PMID- 25126689 TI - Response to Dobie. PMID- 25126691 TI - Relationship between conductive hearing loss and maxillary constriction. AB - OBJECTIVE: To evaluate the relationship between conductive hearing loss and maxillary constriction. METHOD: A total of 120 people, aged from 7 to 40 years, who were referred to an audiologist when taking out health insurance or for school pre-registration check-up, were selected for this study. A total of 60 participants who had hearing threshold levels greater than 15 dB in both ears were chosen as the conductive hearing loss group. The remaining 60, with normal hearing thresholds of less than 15 dB, were used as the control group. All participants were referred to an orthodontic clinic. Participants who had a posterior crossbite and high palatal vault were considered to suffer from maxillary constriction. RESULTS: There were no significant differences between the sex ratios and mean ages of the groups. However, participants with conductive hearing loss were 3.5 times more likely than controls to suffer from maxillary constriction. CONCLUSION: Patients who suffer from conductive hearing loss are likely to show a maxillary abnormality when examined by an orthodontist. PMID- 25126692 TI - Prevalence of altered passive eruption in orthodontically treated and untreated patients. AB - BACKGROUND: Some authors have reported that after orthodontic treatment (OT), a "gummy smile" might develop. Nevertheless, there are no studies in the literature that investigate whether OT increases the presence of altered passive eruption (APE). The primary aim of this cross-sectional study is to evaluate the prevalence of APE after OT (OT group) and compare it with patients who never received OT (control group). A secondary aim is to identify which variables are related to APE. METHODS: The study population consisted of 190 patients (95 patients each in the control and OT groups), providing 1,140 anterior teeth for the clinical examination. The following clinical parameters were assessed: presence or absence of APE, clinical crown length, and gingival biotype, which was divided into three categories: thin-scalloped, thick-flat, and thick scalloped. RESULTS: Twenty-eight patients (29.5%) were diagnosed with APE in the control group and 40 (42.1%) in the OT group, although this difference was not statistically significant (P = 0.07). Furthermore, 34 (75.6%) patients with thick flat biotype were diagnosed with APE, whereas 30 (31.3%) and four (8.2%) with thick-scalloped and thin-scalloped biotypes, respectively, had APE. These differences were statistically significant (P <0.001). CONCLUSIONS: It was concluded that: 1) the prevalence of APE is higher after OT but not to a statistically significant degree and 2) APE is more common in individuals with a thick-flat gingival biotype. PMID- 25126693 TI - Glycated albumin and calprotectin levels in gingival crevicular fluid from patients with periodontitis and type 2 diabetes. AB - BACKGROUND: Patients with diabetes mellitus (DM) have a high prevalence of periodontitis. Periodontitis in these patients is characterized by severe inflammation and tissue breakdown, and its diagnosis is important for cures of periodontitis and DM. The purpose of this study is to investigate the levels of glycated albumin (GA), a DM marker, and calprotectin, an inflammatory marker, in gingival crevicular fluid (GCF) from patients with periodontitis and DM (DM-P). METHODS: The 78 participants in this study were patients with DM, chronic periodontitis (CP), DM-P, and healthy individuals (H). GCF and blood were collected, and GA and calprotectin in GCF were analyzed using Western blotting and enzyme-linked immunosorbent assay. Levels were compared among H, DM, CP, and DM-P groups. Blood GA and glycated hemoglobin (HbA1c) were measured, and the correlation among GCF GA and blood HbA1c or GA levels was investigated. Receiver operating characteristic (ROC) analysis for GCF GA to predict DM was performed. RESULTS: GA was identified in GCF, and its amount/concentration in GCF samples from DM and DM-P were significantly higher than those of non-DM groups (H and CP). Calprotectin amounts in GCF from CP and DM-P were significantly higher than in H and DM groups. GCF GA level was positively correlated with blood HbA1c and GA level. ROC analysis of GCF GA showed an optimal cutoff value to predict DM. CONCLUSIONS: GA showed a high level in GCF from patients with DM. Examination of GA and calprotectin in GCF may be useful for predicting DM-P. PMID- 25126695 TI - Stress Reactivity in Insomnia. AB - This study examined whether individuals with primary insomnia (PI) are more reactive to stress than good sleepers (GS). PI and GS (n = 20 per group), matched on gender and age, completed three nights of polysomnography. On the stress night, participants received a mild electric shock and were told they could receive additional shocks during the night. Saliva samples were obtained for analysis of cortisol and alpha amylase along with self-report and visual analog scales (VAS). There was very little evidence of increased stress on the stress night, compared to the baseline night. There was also no evidence of greater stress reactivity in the PI group for any sleep or for salivary measures. In the GS group, stress reactivity measured by VAS scales was positively associated with an increase in sleep latency in the experimental night on exploratory analyses. Individuals with PI did not show greater stress reactivity compared to GS. PMID- 25126696 TI - Carotid artery dissection associated with an elongated hyoid bone. AB - A 36-year-old man presented with acute cerebral infarction in the right frontal lobe associated with right internal carotid artery dissection (CAD). Enhanced computed tomography revealed right greater horn of the hyoid bone in close proximity to the right internal carotid artery (ICA). It was speculated that mechanical compression of the internal carotid artery by the hyoid bone induced by neck rotation was related to ICA dissection. Greater knowledge of the association between the hyoid bone and the CAD will lead to increased awareness and appropriate diagnosis. PMID- 25126694 TI - Ebselen inhibits hepatitis C virus NS3 helicase binding to nucleic acid and prevents viral replication. AB - The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is both a protease, which cleaves viral and host proteins, and a helicase that separates nucleic acid strands, using ATP hydrolysis to fuel the reaction. Many antiviral drugs, and compounds in clinical trials, target the NS3 protease, but few helicase inhibitors that function as antivirals have been reported. This study focuses on the analysis of the mechanism by which ebselen (2-phenyl-1,2-benzisoselenazol-3 one), a compound previously shown to be a HCV antiviral agent, inhibits the NS3 helicase. Ebselen inhibited the abilities of NS3 to unwind nucleic acids, to bind nucleic acids, and to hydrolyze ATP, and about 1 MUM ebselen was sufficient to inhibit each of these activities by 50%. However, ebselen had no effect on the activity of the NS3 protease, even at 100 times higher ebselen concentrations. At concentrations below 10 MUM, the ability of ebselen to inhibit HCV helicase was reversible, but prolonged incubation of HCV helicase with higher ebselen concentrations led to irreversible inhibition and the formation of covalent adducts between ebselen and all 14 cysteines present in HCV helicase. Ebselen analogues with sulfur replacing the selenium were just as potent HCV helicase inhibitors as ebselen, but the length of the linker between the phenyl and benzisoselenazol rings was critical. Modifications of the phenyl ring also affected compound potency over 30-fold, and ebselen was a far more potent helicase inhibitor than other, structurally unrelated, thiol-modifying agents. Ebselen analogues were also more effective antiviral agents, and they were less toxic to hepatocytes than ebselen. Although the above structure-activity relationship studies suggest that ebselen targets a specific site on NS3, we were unable to confirm binding to either the NS3 ATP binding site or nucleic acid binding cleft by examining the effects of ebselen on NS3 proteins lacking key cysteines. PMID- 25126698 TI - Diagnostic accuracy and risk factors of the different lacunar syndromes. AB - BACKGROUND: The lacunar syndrome is characterized by pure motor, pure sensory, or sensorimotor hemisymptoms without cortical deficits. It may be less predictable for a lacunar infarct (LI) than previously believed. The aims of the present study were to evaluate the diagnostic accuracy of the different lacunar syndromes and investigate factors associated with acute LI on diffusion-weighted imaging (DWI). METHODS: Consecutive patients presenting with an acute lacunar syndrome who were admitted to the stroke unit were enrolled. The patients were examined clinically and underwent magnetic resonance imaging. The sensitivity and specificity of the different lacunar syndromes were assessed using DWI as reference test, and we estimated positive and negative predictive values. Patients were divided into a LI group and a group without LI. Between-group differences were analyzed by chi(2) test, t test, and Mann-Whitney U test, as appropriate. Logistic regression was performed to analyze predictors of LI. Candidate variables were pure motor syndrome, age, gender, hypertension, precerebral or intracerebral stenosis, atrial fibrillation, diabetes, coronary heart disease, and smoking. RESULTS: Eighty-six patients with lacunar syndrome underwent DWI. The positive predictive value of the lacunar syndrome was 65.1% and 75% for the pure motor syndrome. Of the candidate variables, only pure motor syndrome and male gender had significant associations with LI on imaging. CONCLUSIONS: The clinical diagnosis of patients with lacunar syndromes is inaccurate, especially among patients with sensorimotor syndrome. DWI is mandatory for obtaining an accurate diagnosis of the infarct. PMID- 25126697 TI - Recurrence in intracranial atherosclerotic disease: a stenosis-based analysis. AB - BACKGROUND: Intracranial atherosclerotic disease is a common cause of stroke; its incidence and prevalence vary widely by ethnicity. The aim of our study was to analyze the recurrence rate of cerebrovascular events in patients with symptomatic and asymptomatic intracranial stenosis (IS). METHODS: We conducted a historical cohort study including all patients admitted in our hospital for stroke or transient ischemic attack (TIA) during 2011 and 2012 with information on intracranial circulation (ultrasonography and/or computed tomography angiography). We identified patients with symptomatic and asymptomatic IS and studied the recurrence of cerebrovascular events (TIA or ischemic stroke within the territory of the stenosis) for a minimum follow-up period of 6 months after the diagnosis of IS. For the recurrence rate estimation, patients with other potentially embolic diseases (in cervical arteries or heart) were excluded. We calculated the rate of recurrence of cerebrovascular events and performed Kaplan Meier survival curves for symptomatic and asymptomatic IS. RESULTS: We investigated 1302 patients, mean age was 72.41 years (standard deviation 12.75). We identified 218 IS in 158 patients, 77 were symptomatic and 141 were asymptomatic. The recurrence rate of cerebrovascular events was 12.32 per 100 patient-years, with a mean time to recurrence of 1.73 months for symptomatic intracranial stenosis (SIS) and .88 per 100 patient-years for asymptomatic IS (P < .001). CONCLUSIONS: These results indicate a high risk of early recurrence of stroke in the territory of a SIS, highlighting the importance of its early diagnosis and aggressive treatment. PMID- 25126699 TI - Fatal intracranial hemorrhage after intravenous thrombolytic therapy for acute ischemic stroke associated with cancer-related nonbacterial thrombotic endocarditis. AB - Nonbacterial thrombotic endocarditis (NBTE) is associated with hypercoagulability in patients with inflammatory states such as cancer and autoimmune diseases. Cardiac vegetations caused by NBTE often lead to life-threatening systemic thromboembolism that most frequently affects the brain, spleen, and kidneys. A 54 year-old woman diagnosed with ovarian cancer suddenly developed back pain and left hemiparesis. Although intravenous alteplase (rt-PA) therapy was administered to treat hyperacute ischemic infarction detected by magnetic resonance imaging, intracranial hemorrhage occurred in the left hemisphere several hours later as the patient started to lose consciousness. Transthoracic echocardiography then detected aseptic vegetations on the mitral and aortic valves, indicating NBTE associated with ovarian cancer. Because therapies for NBTE are limited to heparinization and control of underlying diseases, thrombolytic therapy for acute embolic stroke in NBTE has not yet been validated. We postulated that thrombolytic therapy for cancer-related NBTE might easily cause hemorrhagic complications because cancer-related NBTE is often similar to the state of disseminated intravascular coagulation. PMID- 25126700 TI - Screening of the GPX3 gene identifies the "T" allele of the SNP -861A/T as a risk for ischemic stroke in young Asian Indians. AB - BACKGROUND: Deficiency of plasma glutathione peroxidase (GPx-3) has been associated with platelet-dependent thrombosis. Single-nucleotide polymorphisms (SNPs) in the promoter region of GPX3 gene have been found associated with the risk for ischemic stroke in Caucasian populations. The aim of our present study was to evaluate the impact of genetic variations in the GPX3 gene and plasma GPx 3 antigen levels on ischemic stroke in young Asian Indians. METHODS: One hundred patients with ischemic stroke and 200 age- and sex-matched controls were studied. Genetic analysis for the study population was done by a combination of variant screening using single-stranded conformation polymorphism and final genotyping by polymerase chain reaction-restriction fragment length polymorphism and allele specific polymerase chain reactions. Plasma GPx-3 antigen levels were evaluated using commercial kits. Data were analyzed using genetic analysis software and statistical tools. RESULTS: Significantly higher GPx-3 levels were observed in controls compared with patients (controls 26.37 +/- 3.66 MUg/mL and patients 22.83 +/- 4.57 MUg/mL, P < .001). Only the SNP -861A/T was found associated with stroke phenotype (P < .0001). The SNP -568T/C was observed to significantly influence plasma GPx-3 levels (P < .05). The haplotype carrying the risk "T" allele of SNP -861A/T was significantly over-represented in patients with stroke (P < .0001). CONCLUSIONS: The T allele of -861A/T is a risk allele for the ischemic stroke phenotype. The -861A/T and -568T/C SNPs may show a statistically significant association with both plasma GPx-3 antigen levels and the stroke phenotype in a larger sample size. PMID- 25126701 TI - Relevance of Health Knowledge in Reporting Maternal Health Complications and Use of Maternal Health Care in India. AB - We measured levels of women's health knowledge and their association with the reporting of maternal health complications and related health care use. We found that women with higher levels of health knowledge reported more pregnancy and postnatal complications, and used more maternal health care services. Education has a positive impact on health, but education alone is not enough to ensure recognizing and reporting of health complications and increasing the demand for maternal health care services. We conclude that the provision of health education for women will help them to identify maternal health complications and improve their reporting and related health care use. PMID- 25126702 TI - Anesthesia complications as a childbirth patient safety indicator. AB - BACKGROUND: The Agency for Healthcare Research and Quality (AHRQ) has established multiple sets of indicators for quality monitoring and improvement. One such set is the patient safety indicators (PSIs), which focuses on potentially preventable hospital complications after surgeries, procedures, and childbirth. Our objective in this study was to determine the prevalence of childbirth-related anesthesia complications by method of delivery and to evaluate the variation in complication rates across hospitals using the AHRQ PSI methodology and a modification specific to childbirth with the goal of determining the relevance of tracking anesthesia complications as a potential PSI for childbirth. METHODS: The technical specifications of the experimental Anesthesia Complication Quality Indicator, one of the PSI defined by AHRQ, were modified to create a childbirth-specific indicator that included all childbirth admissions (vaginal and cesarean deliveries) and complications from general and neuraxial anesthesia/analgesia. Using California hospital discharge data, we calculated hospital-specific rates, adjusting for age, race/ethnicity, and pregnancy complications. RESULTS: A total of 508,842 deliveries occurred in 254 hospitals in California in 2009. Hospitals with <200 annual deliveries (N = 12) were excluded from analyses. Among 242 hospitals, the rate of anesthesia complications was 0.13% for the standard AHRQ study population (adult surgical admissions, which included cesarean deliveries). The childbirth-specific rate of anesthesia complications was 0.31%. When stratified by method of delivery, complication rates were 0.49% for cesarean delivery and 0.22% for vaginal delivery (P < 0.0001). The unadjusted mean (SD) was 0.34% (0.34%), with range (0%-2.46%). The rates of 13 hospitals (including their 95% confidence limits) remained in the upper quartile as outliers, with adjusted rates from 0.52% to 2.13%. CONCLUSIONS: Rates of childbirth-related anesthesia complications may provide an opportunity to identify hospitals with extreme rates that may provide insights into systematic ways to improve patient safety. PMID- 25126703 TI - Glycogen synthase kinase-3beta inhibition prevents remifentanil-induced postoperative hyperalgesia via regulating the expression and function of AMPA receptors. AB - BACKGROUND: Many studies have confirmed that brief remifentanil exposure can enhance pain sensitivity. We previously reported that activation of glycogen synthase kinase-3beta (GSK-3beta) contributes to remifentanil-induced hyperalgesia via regulating N-methyl-D-aspartate receptor plasticity in the spinal dorsal horn. In this study, we demonstrated that GSK-3beta inhibition prevented remifentanil-induced postoperative hyperalgesia via regulating alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression and function in the spinal dorsal horn. METHODS: Using a rat model of remifentanil-induced incision hyperalgesia, mechanical and thermal pain was tested 1 day before infusion and 2 hours, 6 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after infusion. Western blot analysis was used to detect AMPAR subunit (GluR1 and GluR2) trafficking, AMPAR phosphorylation status, and GSK-3beta activity in the spinal dorsal horn. Furthermore, whole-cell patch-clamp recording was used to analyze the effect of GSK-3beta inhibition on AMPAR-induced current in the spinal dorsal horn. RESULTS: Membrane AMPAR subunit GluR1 was upregulated in the spinal cord in remifentanil-induced postoperative hyperalgesia rats (275 +/- 36.54 [mean +/- SD] vs 100 +/- 9.53, P = 0.0009). Selective GSK-3beta inhibitors, LiCl and TDZD, treatment ameliorates remifentanil-induced postoperative hyperalgesia, and this was associated with the downregulated GluR1 subunit in the membrane fraction (254 +/- 23.51 vs 119 +/- 14.74, P = 0.0027; 254 +/- 23.51 vs 124 +/- 9.35, P = 0.0032). Moreover, remifentanil incubation increased the amplitude and the frequency of AMPAR-induced current in dorsal horn neurons (61.09 +/- 9.34 pA vs 32.56 +/- 6.44 pA, P = 0.0009; 118.32 +/- 20.33 milliseconds vs 643.67 +/- 43.29 milliseconds, P = 0.0002), which was prevented with the application of LiCl and TDZD, respectively. Remifentanil-induced postoperative pain induced an increase in pGluR1 Ser845 and Rab5, which was prevented with the application of LiCl and TDZD. CONCLUSIONS: These results indicate that amelioration of remifentanil-induced postoperative hyperalgesia by GSK-3beta inhibition is attributed to downregulated AMPAR GluR1 expression in the membrane fraction and inhibition of AMPAR function via altering pGluR1 and Rab5 expression in the spinal dorsal horn. PMID- 25126704 TI - What epidural opioid results in the best analgesia outcomes and fewest side effects after surgery?: a meta-analysis of randomized controlled trials. AB - BACKGROUND: Epidural opioids are widely used for central neuraxial blockade and postoperative analgesia. However, differences in analgesic efficacy and side effect rates among individual opioids remain controversial. METHODS: We conducted a random-effects meta-analysis of randomized controlled trials that compared at least 2 continuous epidural infusions for acute postoperative analgesia over at least 24 hours. Individual study data were weighted by the inverse-variance method. Visual analog scale (VAS) pain scores were the primary outcome. Secondary outcomes included opioid side effects, such as pruritus, postoperative nausea and vomiting (PONV), sedation, hypotension, and respiratory depression. RESULTS: Nineteen of the 24 trials included compared 2 of the following opioids: morphine, fentanyl, or sufentanil. The total subjects studied were 1513. Pooled analysis by type of surgery showed no clinically significant differences in VAS pain scores at any time after surgery. There were more PONV (OR = 1.91; 95% CI, 1.14-3.18; P = 0.014) and perhaps pruritus (OR = 1.64; 95% CI, 0.98-2.76; P = 0.162) with morphine compared to fentanyl. Total opioid consumption differed only in the trials comparing morphine and fentanyl, where patients in the morphine group required 1.2 mg (of morphine equivalent) less (95% CI, 0.27-2.18). Use of analgesic adjuncts was similar for all but 2 studies. CONCLUSIONS: Analgesic outcome, in terms of VAS pain score, was similar between the epidural opioids studied. These similarities in analgesia may reflect the common practices of concurrently using epidural local anesthetics with the opioids and titrating infusion rates according to a patient's pain status. With respect to side effects, the incidence of PONV and possibly pruritus was higher with morphine compared with fentanyl, despite there being similar total opioid consumption between those groups. PMID- 25126705 TI - Hypersensitivity reactions to intravenous lipid emulsion in swine: relevance for lipid resuscitation studies. AB - BACKGROUND: Reports in the recent experimental literature have provided contradicting results in different animal species regarding the efficacy of IV lipid emulsion (ILE) in the reversal of cardiovascular and central nervous system symptoms of local anesthetic and other lipophilic drug overdoses. In particular, ILE seemed to be effective in rats, rabbits, dogs, and humans, but not in swine, for which it not only failed to reverse the adverse effects of anesthetics, but the animals also developed a generalized cutaneous mottling or a dusky appearance immediately after ILE, suggestive of another type of toxicity. The latter symptoms arise in complement (C) activation-related pseudoallergy, a hypersensitivity reaction to particulate drugs and agents. METHODS: Ten Yorkshire swine (15-20 kg) were sedated with ketamine and anesthetized with isoflurane. ILE 1.5 and 5 mL/kg 20% was administered via the ear vein while pulmonary arterial pressure, systemic arterial blood pressure, electrocardiogram, and end-tidal CO2 were recorded continuously. Thromboxane was measured in blood collected at baseline and 2 and 10 minutes after injections. Complement activation by lipid emulsion was also assessed in vitro with soluble terminal complement complex (SC5b-9) and sheep red blood cell assays. RESULTS: Significant increases were observed in the pulmonary pressure (median [interquartile range]) within minutes after the administration of ILE, both at doses 1.5 and 5 mL/kg (15 [12-16.5] to 18.5 [16-20] mm Hg, P = 0.0058 and 15.5 [13-17.25] to 39.5 [30.5-48.5], respectively). The systemic arterial blood pressure increased, and the heart rate decreased after both injections. Thromboxane B2 concentration (median [interquartile range]) in the blood plasma increased from a baseline of 617.3 [412.4-920] to 1132 [597.9-1417] pg/mL (P = 0.0055) and from 1276 [1200-2581] to 4046 [2946-8442] pg/mL (P = 0.0017) after the administration of 1.5 and 5 mL/kg ILE, respectively. Intralipid did not cause in vitro complement activation in human serum. CONCLUSIONS: ILE causes clinically significant hemodynamic changes in pigs, in concert with significant increases in the plasma thromboxane concentration. However, the in vitro tests did not confirm involvement of the complement system in human sera, leaving the underlying mechanism of these findings in doubt. Nonetheless, the observed hemodynamic and biochemical effects of ILE serve as a caveat that the pig is not an ideal model for the study of interventions involving ILE. PMID- 25126706 TI - Hybrid nanoparticles by step-growth Sonogashira coupling in disperse systems. AB - Organic/inorganic hybrid nanoparticles were prepared by a Sonogashira miniemulsion polymerization of dibromo aryl and diethynyl aryl monomers and modified titanium dioxide and cadmium selenide nanocrystals, respectively. The poly(arylene ethynylene) microstructure and polymerization rates, as reflected by monomer reactivity, decisively impact whether inorganic guest particles can be trapped to afford a uniform distribution within a newly formed polymer particle or phase separate. This issue was found to be more critical for the TiO2 rods studied here. To this end, the compatibility of the organic and inorganic portions could be improved substantially by the incorporation of functional groups that bind the inorganic surface to the polymer via an appropriate termonomer. This concept, in combination with rapid particle formation via a postpolymerization dispersion of a premade poly(arylene ethynylene)/TiO2 composite as an alternative technique, yielded composite particles with a high loading of the inorganic nanoparticles. PMID- 25126708 TI - Role of atrial natriuretic Peptide in oxytocin induced cardioprotection. AB - BACKGROUND: The purpose of this study was to determine whether endogenous atrial natriuretic peptide (ANP) contributes to the protective effect of neurohypophysial hormone oxytocin (OT) in heart preconditioning. METHODS: Sprague Dawley male rats were subjected to 25 min regional ischaemia and 120 min reperfusion and were divided into eight groups. Oxytocin or an equivalent volume of saline was administrated intraperitoneally, 30 min before ischaemia. The OT receptor antagonist (atosiban), ANP receptor antagonist (anantin) and nitric oxide synthase inhibitor (L-NAME) were injected 10 min before OT. In other groups, atosiban, anantin and L-NAME were only administered 40 min prior to ischaemia. RESULTS: Compared with the ischaemia/reperfusion group (I/R), alterations in infarct size, biochemical parameters [LDH (lactate dehydrogenase), CK-MB (creatine kinase-MB), MDA (malondialdehyde) plasma levels] and severity of ventricular arrhythmia due to I/R injury were attenuated and VF was abolished by OT treatment. These OT effects were eliminated by OT and ANP receptor blockers and nitric oxide synthase inhibitor, but anantin did not reverse the effect of OT in lipid peroxidation. CONCLUSIONS: These findings demonstrate an important contributory role of ANP in the OT induced protection in myocardial ischaemia reperfusion. OT also reduced lipid peroxidation with a NO-dependent mechanism. PMID- 25126707 TI - Metabolic phenotyping reveals a lipid mediator response to ionizing radiation. AB - Exposure to ionizing radiation has dramatically increased in modern society, raising serious health concerns. The molecular response to ionizing radiation, however, is still not completely understood. Here, we screened mouse serum for metabolic alterations following an acute exposure to gamma radiation using a multiplatform mass-spectrometry-based strategy. A global, molecular profiling revealed that mouse serum undergoes a series of significant molecular alterations following radiation exposure. We identified and quantified bioactive metabolites belonging to key biochemical pathways and low-abundance, oxygenated, polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to gamma radiation induced a significant increase in the serum levels of ether phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of arachidonic acid increased, whereas levels of anti-inflammatory metabolites of omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic biosignature that could be utilized as an indicator of radiation exposure and as novel target for therapeutic intervention. Monitoring such a molecular response to radiation exposure might have implications not only for radiation pathology but also for countermeasures and personalized medicine. PMID- 25126709 TI - [Myxoid/round cell liposarcoma of the brachial plexus]. AB - Myxoid/round cell liposarcoma is a soft tissue sarcoma that is extremely rare in the brachial plexus. We report a case of a myxoid/round cell liposarcoma originating in the brachial plexus that was surgically resected and evolved well, with no deficit or recurrence after 2 years of follow-up. To date, there has been no other case of this sarcoma in the literature. PMID- 25126710 TI - [Endovascular versus surgical treatment in subarachnoid haemorrhage: Cost analysis]. AB - OBJECTIVES: To analyse costs of endovascular versus surgical treatment in 80 patients with aneurysmal subarachnoid haemorrhage (aSAH). MATERIAL AND METHODS: We analysed data on 80 consecutive patients with aSAH between January 2010 and June 2011. Endovascular treatment was used in 57 patients and surgical in 23 patients. Demographic (gender and age) and clinical data (Hunt-Hess and Fisher scales), length of stay (ICU and ward) and results at 6 months (Glasgow outcome scale,[GOS]) were collected. Costs including stay, follow-up, complications and retreatments were calculated. RESULTS: Age was higher in the endovascular group (statistically significant). There were no differences between the 2 groups in Hunt-Hess and Fisher scales. Results at 6 months were also similar, although slightly better in the surgical group. Length of stay was longer in surgical patients, both in ICU (mean 1.4 days) and ward (1.7 days). Hospitalisation length was also related to age and Hunt-Hess and Fisher scales. Costs from embolisation devices, follow-up and retreatment (12% in this series) made final endovascular treatment 4.1% more expensive than surgical treatment (?35,835 versus ?34,404). Endovascular procedure (including retreatments) was 110% more expensive than surgical treatment (?8,015 versus ?3,817). CONCLUSIONS: There are no differences between the 2 treatments in terms of morbidity and mortality. Stability of surgical treatment was higher than that of endovascular, with better occlusion and lower retreatment rates. Endovascular treatment is more expensive in ruptured aneurysms, principally due to embolisation device costs, long-term follow-up and retreatments, in retreatments, in spite of shorter hospital stay. In incidental aneurysms, which usually need shorter hospitalisation, differences between the 2 treatments could be even larger. PMID- 25126711 TI - Detection of parasitic plant suicide germination compounds using a high throughput Arabidopsis HTL/KAI2 strigolactone perception system. AB - Strigolactones are terpenoid-based plant hormones that act as communication signals within a plant, between plants and fungi, and between parasitic plants and their hosts. Here we show that an active enantiomer form of the strigolactone GR24, the germination stimulant karrikin, and a number of structurally related small molecules called cotylimides all bind the HTL/KAI2 alpha/beta hydrolase in Arabidopsis. Strigolactones and cotylimides also promoted an interaction between HTL/KAI2 and the F-box protein MAX2 in yeast. Identification of this chemically dependent protein-protein interaction prompted the development of a yeast-based, high-throughput chemical screen for potential strigolactone mimics. Of the 40 lead compounds identified, three were found to have in planta strigolactone activity using Arabidopsis-based assays. More importantly, these three compounds were all found to stimulate suicide germination of the obligate parasitic plant Striga hermonthica. These results suggest that screening strategies involving yeast/Arabidopsis models may be useful in combating parasitic plant infestations. PMID- 25126712 TI - Catalyst design in oxidation chemistry; from KMnO4 to artificial metalloenzymes. AB - Oxidation reactions are an important part of the synthetic organic chemist's toolkit and continued advancements have, in many cases, resulted in high yields and selectivities. This review aims to give an overview of the current state-of the-art in oxygenation reactions using both chemical and enzymatic processes, the design principles applied to date and a possible future in the direction of hybrid catalysts combining the best of chemical and natural design. PMID- 25126713 TI - Inhibitory effects of p-alkylaminophenol on melanogenesis. AB - Melanin protects the skin against ultraviolet (UV) rays. It is produced in excess by UV radiation, which causes skin disorders and pigmentation. Retinoic acid (RA) decreases the levels of epidermal melanin by suppressing the expression of melanogenic enzymes including tyrosinase, which is the rate-limiting enzyme in melanin synthesis. However, RA shows inflammatory effects on the skin. In an effort to develop potent inhibitors of melanin synthesis, new aminophenol derivatives were synthesized based on structure-activity relationship studies of N-(4-hydroxyphenyl)retinamide (1), a derivative of RA. We investigated the inhibitory effects of a series of aminophenols on melanogenesis using B16 melanoma cells. p-Decylaminophenol (3) was the most potent agent examined, showing significant inhibition of B16 tyrosinase activities at concentrations less than what was required to achieve a similar level of inhibition by the well known tyrosinase inhibitor, kojic acid. Compound 3 decreased melanin content and inhibited protein and mRNA expression for the tyrosinase-related protein-1 (TRP 1). It also inhibited the microphthalmia-associated transcription factor (MITF), a master transcription factor in melanogenesis. Compound 3 suppressed MEK/ERK signal pathways involved in the activation and expression of MITF. The data indicate that 3 inhibits TRP-1 expression by decreasing MITF expression through suppressing MEK/ERK signal pathways. This results in the reduction of melanin in B16 cells. Compound 3 might be an alternative to RA as a potent inhibitor of melanogenesis. PMID- 25126714 TI - Design, stereoselective synthesis, configurational stability and biological activity of 7-chloro-9-(furan-3-yl)-2,3,3a,4-tetrahydro-1H-benzo[e]pyrrolo[2,1 c][1,2,4]thiadiazine 5,5-dioxide. AB - Chiral 5-arylbenzothiadiazine derivatives have recently attracted particular attention because they exhibit an interesting pharmacological activity as AMPA receptor (AMPAr) positive modulators. However, investigations on their configurational stability suggest a rapid enantiomerization in physiological conditions. In order to enhance configurational stability, preserving AMPAr activity, we have designed the novel compound (R,S)-7-chloro-9-(furan-3-yl) 2,3,3a,4-tetrahydro-1H-benzo[e]pyrrolo[2,1-c][1,2,4]thiadiazine 5,5-dioxide bearing a pyrrolo moiety coupled with the 5-(furan-3-yl) substituent on benzothiadiazine core. A stereoselective synthesis was projected to obtain single enantiomer of the latter compound. Absolute configuration was assigned by X-ray crystal structure. Patch clamp experiments evaluating the activity of single enantiomers as AMPAr positive allosteric modulator showed that R stereoisomer is the active component. Molecular modeling studies were performed to explain biological results. An on-column stopped-flow bidimensional recycling HPLC procedure was applied to obtain on a large scale the active enantiomer with enantiomeric enrichment starting from the racemic mixture of the compound. PMID- 25126715 TI - Mechanical compression insults induce nanoscale changes of membrane-skeleton arrangement which could cause apoptosis and necrosis in dorsal root ganglion neurons. AB - In a primary spinal cord injury, the amount of mechanical compression insult that the neurons experience is one of the most critical factors in determining the extent of the injury. The ultrastructural changes that neurons undergo when subjected to mechanical compression are largely unknown. In the present study, using a compression-driven instrument that can simulate mechanical compression insult, we applied mechanical compression stimulation at 0.3, 0.5, and 0.7 MPa to dorsal root ganglion (DRG) neurons for 10 min. Combined with atomic force microscopy, we investigated nanoscale changes in the membrane-skeleton, cytoskeleton alterations, and apoptosis induced by mechanical compression injury. The results indicated that mechanical compression injury leads to rearrangement of the membrane-skeleton compared with the control group. In addition, mechanical compression stimulation induced apoptosis and necrosis and also changed the distribution of the cytoskeleton in DRG neurons. Thus, the membrane-skeleton may play an important role in the response to mechanical insults in DRG neurons. Moreover, sudden insults caused by high mechanical compression, which is most likely conducted by the membrane-skeleton, may induce necrosis, apoptosis, and cytoskeletal alterations. PMID- 25126718 TI - Trachelorraphy in cases of recurrent second trimester loss and prior failed vaginal cerclage. AB - OBJECTIVE: To evaluate the obstetric results of trachelorraphy in the prevention of recurrent second trimester loss in cases of prior failed vaginal cerclage. STUDY DESIGN: Data were collected retrospectively and prospectively from medical records. The analysis examined data for 18 women who underwent trachelorraphy between 2004 and 2013 at a tertiary referral unit in France. All patients in this high-risk population had a history of two or more second trimester losses, or one second trimester loss and one preterm labour, and at least one prior failed transvaginal cerclage. The main outcome measures were: livebirth rate; rate of second trimester loss; and surgical complications. RESULTS: Twenty pregnancies were conceived in 16 patients following trachelorraphy. Three patients experienced two pregnancies. Among the 20 pregnancies, there was one case of fetal loss in the first trimester; this pregnancy was excluded from the analysis. Of the remaining 19 pregnancies, there were nine (47%) term deliveries (after 37 weeks of gestation), seven (32%) preterm deliveries and three (16%) second trimester losses. The overall fetal survival rate was 84%. Surgical outcomes were excellent, with no complications. CONCLUSION: Trachelorraphy is a safe, reproducible, easy-to-learn procedure for the prevention of recurrent second trimester loss in cases of prior failed vaginal cerclage. The procedure has encouraging and favourable perinatal outcomes in patients with a poor obstetric history. PMID- 25126716 TI - Characterization of long non-coding RNA transcriptome in clear-cell renal cell carcinoma by next-generation deep sequencing. AB - INTRODUCTION: Long non-coding RNA (lncRNA) have proven to play key roles in cell physiology from nuclear organization and epigenetic remodeling to post transcriptional regulation. Last decade, gene expression based-classifications have been developed in clear-cell renal cell carcinoma (ccRCC) to identify distinct subtypes of disease and predict patient's outcome. However, there are no current lncRNA comprehensive characterizations in ccRCC. PATIENTS AND METHODS: RNA-sequencing profiles of 475 primary ccRCC samples from the Cancer Genome Atlas (TCGA) were used to assess expressed lncRNA and identify lncRNA-based classification. In addition, integrative analysis was performed to correlate tumor subtypes with copy-number alterations and somatic mutations. RESULTS: Using stringent criteria, we identified 1934 expressed lncRNA and assessed their chromatin marks. Unsupervised clustering unravels four lncRNA subclasses in ccRCC associated with distinct clinicopathological and genomic features of this disease. Cluster C2 (23.4%) defines the most aggressive tumours, with the highest Fuhrman grade and stage and the worst overall survival time. Furthermore, cluster C2 is enriched for 9p deletion and chromatin remodeler BAP1 somatic mutations. Interestingly, cluster C4 (7.8%) is related to a tumor subtype arising from the distal tubules of the nephron. Consistent with its distinct ontogeny, cluster C4 is devoid of classical alterations seen in ccRCC, bears frequent 1p deletion and 17q gain, and is enriched for MiTF/TFE translocations. In addition, reexaminations of copy-number data from one side and tumor histology by pathologists from the other side reveal misclassified tumors within C4 cluster including chromophobe RCC and clear cell papillary RCC. CONCLUSION: This study establishes a foundation for categorizing lncRNA subclasses, which may contribute to understand tumor ontogeny and help predicting patients' outcome in ccRCC. PMID- 25126717 TI - The extent of diffusion MRI markers of neuroinflammation and white matter deterioration in chronic schizophrenia. AB - In a previous study we have demonstrated, using a novel diffusion MRI analysis called free-water imaging, that the early stages of schizophrenia are more likely associated with a neuroinflammatory response and less so with a white matter deterioration or a demyelination process. What is not known is how neuroinflammation and white matter deterioration change along the progression of the disorder. In this study we apply the free-water measures on a population of 29 chronic schizophrenia subjects and compare them with 25 matching controls. Our aim was to compare the extent of free-water imaging abnormalities in chronic subjects with the ones previously obtained for subjects at their first psychotic episode. We find that chronic subjects showed a limited extent of abnormal increase in the volume of the extracellular space, suggesting a less extensive neuroinflammatory response relative to patients at the onset of schizophrenia. At the same time, the chronic schizophrenia subjects had greater extent of reduced fractional anisotropy compared to the previous study, suggesting increased white matter deterioration along the progression of the disease. Our findings substantiate the role of neuroinflammation in the earlier stages of the disorder, and the effect of neurodegeneration that is worsening in the chronic phase. PMID- 25126719 TI - [Neonatal enterovirus infections reported in France in 2012]. AB - Enteroviruses (EVs) are among the most common viruses infecting humans. One-third of EV infections affect children under 1 year of age. Neonatal EV infections lead to a wide range of clinical manifestations, from mild febrile illness to severe, potentially fatal sepsis-like conditions with multiorgan failure. EV detections by serotype are reported by the National Reference Centre for EV Infections Lyon on a monthly basis. Demographic, clinical, and biological data were also collected in neonates hospitalized in 2012 for EV infection. Two subgroups were identified according to the beginning of symptoms: until 8 days of life (D8) or strictly after D8. There were 120 neonatal EV infections. Before D8, children with severe infection were born more prematurely with a low birth weight. The EVs most commonly detected in neonates were CV-B4 and E-11. Risk factors for severe EV infections included liver (73% before D8) and hematological damage (thrombocytopenia, 82%; coagulopathy, 64% before D8). This study suggests that systematic serotyping of neonatal EV infections and biological monitoring of liver function could be useful for early identification of children at high risk of clinical severity and fatality. PMID- 25126720 TI - Post-appendectomy surgical site infection rate after using an antimicrobial film incise drape: a prospective study. AB - BACKGROUND: An appendectomy is a contaminated or potentially dirty surgical procedure that can be associated with surgical site infection (SSI). METHODS: A single-center unblinded prospective cohort study examined the role of antimicrobial incise film drapes in lowering the rate of SSI after appendectomy. Any patient aged 12 years or older who was scheduled for open appendectomy for acute appendicitis was included. Patients were assigned to two groups. Group 1 (n=52) had the standard five-minute skin preparation with 10% povidone-iodine soap followed by the application of an antimicrobial film incise drape, and group 2 (n=39) had the standard skin preparation alone. RESULTS: Six (11.5%) of the 52 patients who had the antimicrobial film incise drape and two (5.1%) of the 39 patients who did not have the drape developed SSI (p=NS). Of the six patients in the antimicrobial film group with post-operative SSI, three had a perforated appendix, two had a gangrenous appendix, and one had an inflamed appendix. In group 2, one patient had an inflamed appendix and the other had a perforated appendix. The median length of stay in the hospital was two days (range 1-11 days) for both groups. CONCLUSION: Our study did not support the view that antimicrobial film incise drapes can lower the rate of post-appendectomy SSI. Moreover, the length of stay was not minimized by the use of these drapes. PMID- 25126722 TI - The community structure of the global corporate network. AB - We investigate the community structure of the global ownership network of transnational corporations. We find a pronounced organization in communities that cannot be explained by randomness. Despite the global character of this network, communities reflect first of all the geographical location of firms, while the industrial sector plays only a marginal role. We also analyze the meta-network in which the nodes are the communities and the links are obtained by aggregating the links among firms belonging to pairs of communities. We analyze the network centrality of the top 50 communities and we provide a quantitative assessment of the financial sector role in connecting the global economy. PMID- 25126721 TI - Effects of 28Si ions, 56Fe ions, and protons on the induction of murine acute myeloid leukemia and hepatocellular carcinoma. AB - Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or 600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that 28Si or 56Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, 28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members. PMID- 25126723 TI - The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy. AB - Receptor-mediated mitophagy is one of the major mechanisms of mitochondrial quality control essential for cell survival. We previously have identified FUNDC1 as a mitophagy receptor for selectively removing damaged mitochondria in mammalian systems. A critical unanswered question is how receptor-mediated mitophagy is regulated in response to cellular and environmental cues. Here, we report the striking finding that BCL2L1/Bcl-xL, but not BCL2, suppresses mitophagy mediated by FUNDC1 through its BH3 domain. Mechanistically, we demonstrate that BCL2L1, but not BCL2, interacts with and inhibits PGAM5, a mitochondrially localized phosphatase, to prevent the dephosphorylation of FUNDC1 at serine 13 (Ser13), which activates hypoxia-induced mitophagy. Our results showed that the BCL2L1-PGAM5-FUNDC1 axis is critical for receptor-mediated mitophagy in response to hypoxia and that BCL2L1 possesses unique functions distinct from BCL2. PMID- 25126724 TI - MIR125B1 represses the degradation of the PML-RARA oncoprotein by an autophagy lysosomal pathway in acute promyelocytic leukemia. AB - Acute promyelocytic leukemia (APL) is characterized by the t(15;17)-associated PML-RARA fusion gene. We have previously found that MIR125B1 is highly expressed in patients with APL and may be associated with disease pathogenesis; however, the mechanism by which MIR125B1 exerts its oncogenic potential has not been fully elucidated. Here, we demonstrated that MIR125B1 abundance correlates with the PML RARA status. MIR125B1 overexpression enhanced PML-RARA expression and inhibited the ATRA-induced degradation of the PML-RARA oncoprotein. RNA-seq analysis revealed a direct link between the PML-RARA degradation pathway and MIR125B1 arrested differentiation. We further demonstrated that the MIR125B1-mediated blockade of PML-RARA proteolysis was regulated via an autophagy-lysosomal pathway, contributing to the inhibition of APL differentiation. Furthermore, we identified DRAM2 (DNA-damage regulated autophagy modulator 2), a critical regulator of autophagy, as a novel target that was at least partly responsible for the function of MIR125B1 involved in autophagy. Importantly, the knockdown phenotypes for DRAM2 are similar to the effects of overexpressing MIR125B1 as impairment of PML-RARA degradation, inhibition of autophagy, and myeloid cell differentiation arrest. These effects of MIR125B1 and its target DRAM2 were further confirmed in an APL mouse model. Thus, MIR125B1 dysregulation may interfere with the effectiveness of ATRA-mediated differentiation through an autophagy-dependent pathway, representing a novel potential APL therapeutic target. PMID- 25126725 TI - The nascent polypeptide-associated complex is essential for autophagic flux. AB - The ribosome-associated nascent polypeptide-associated complex (NAC) is involved in multiple cotranslational processes, including protein transport into the ER and mitochondria, and also acts as a chaperone to assist protein folding. Here we demonstrated that NAC is also essential for autophagic degradation of a variety of protein aggregates in C. elegans. Loss of function of NAC impairs lysosome function, resulting in accumulation of autophagic substrates in enlarged autolysosomes. Knockdown of mammalian NAC also causes accumulation of nondegradative autolysosomes. Our study revealed that NAC plays an evolutionarily conserved role in the autophagy pathway and thus in maintaining protein homeostasis under physiological conditions. PMID- 25126728 TI - Human GABARAP can restore autophagosome biogenesis in a C. elegans lgg-1 mutant. AB - We recently described in C. elegans embryos, the acquisition of specialized functions for orthologs of yeast Atg8 (e.g., mammalian MAP1LC3/LC3) in allophagy, a selective and developmentally regulated autophagic process. During the formation of double-membrane autophagosomes, the ubiquitin-like Atg8/LC3 proteins are recruited to the membrane through a lipidation process. While at least 6 orthologs and paralogs are present in mammals, C. elegans only possesses 2 orthologs, LGG-1 and LGG-2, corresponding to the GABARAP-GABARAPL2/GATE-16 and the MAP1LC3 families, respectively. During allophagy, LGG-1 acts upstream of LGG 2 and is essential for autophagosome biogenesis, whereas LGG-2 facilitates their maturation. We demonstrated that LGG-2 directly interacts with the HOPS complex subunit VPS-39, and mediates the tethering between autophagosomes and lysosomes, which also requires RAB-7. In the present addendum, we compared the localization of autophagosomes, endosomes, amphisomes, and lysosomes in vps-39, rab-7, and lgg 2 depleted embryos. Our results suggest that lysosomes interact with autophagosomes or endosomes through a similar mechanism. We also performed a functional complementation of an lgg-1 null mutant with human GABARAP, its closer homolog, and showed that it localizes to autophagosomes and can rescue LGG-1 functions in the early embryo. PMID- 25126730 TI - Folding into an autophagosome: ATG5 sheds light on how plants do it. AB - Autophagosomes arise in yeast and animals from the sealing of a cup-shaped double membrane precursor, the phagophore. The concerted action of about 30 evolutionarily conserved autophagy related (ATG) proteins lies at the core of this process. However, the mechanisms allowing phagophore generation and its differentiation into a sealed autophagosome are still not clear in detail, and very little is known in plants. This is due in part to the scarcity of structurally informative, real-time imaging data of ATG proteins at the phagophore site. Among these, the ATG5 complex directs anchoring of ATG8 to the phagophore, an event required for membrane expansion. Detailed real-time and 3D imaging of ATG5, ATG8, and an ER marker at the expanding phagophore allowed us to propose a model for autophagosome formation in plants. This model implies tight connections of the growing phagophore with the outer face of the cortical endoplasmic reticulum and prompts new questions on the mechanism of autophagosome biogenesis. PMID- 25126729 TI - Berberine attenuates autophagy in adipocytes by targeting BECN1. AB - The lysosomal degradation pathway, autophagy, is essential for the maintenance of cellular homeostasis. Recently, autophagy has been demonstrated to be required in the process of adipocyte conversion. However, its role in mature adipocytes under physiological and pathological conditions remains unclear. Here, we report a major function of BECN1 in the regulation of basal autophagy in mature adipocytes. We also show that berberine, a natural plant alkaloid, inhibits basal autophagy in adipocytes and adipose tissue of mice fed a high-fat diet via downregulation of BECN1 expression. We further demonstrate that berberine has a pronounced effect on the stability of Becn 1 mRNA through the Mir30 family. These findings explore the potential of BECN1 as a key molecule and a drug target for regulating autophagy in mature adipocytes. PMID- 25126726 TI - FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation. AB - Birt-Hogg-Dube (BHD) syndrome is a rare autosomal dominant condition caused by mutations in the FLCN gene and characterized by benign hair follicle tumors, pneumothorax, and renal cancer. Folliculin (FLCN), the protein product of the FLCN gene, is a poorly characterized tumor suppressor protein, currently linked to multiple cellular pathways. Autophagy maintains cellular homeostasis by removing damaged organelles and macromolecules. Although the autophagy kinase ULK1 drives autophagy, the underlying mechanisms are still being unraveled and few ULK1 substrates have been identified to date. Here, we identify that loss of FLCN moderately impairs basal autophagic flux, while re-expression of FLCN rescues autophagy. We reveal that the FLCN complex is regulated by ULK1 and elucidate 3 novel phosphorylation sites (Ser406, Ser537, and Ser542) within FLCN, which are induced by ULK1 overexpression. In addition, our findings demonstrate that FLCN interacts with a second integral component of the autophagy machinery, GABA(A) receptor-associated protein (GABARAP). The FLCN-GABARAP association is modulated by the presence of either folliculin-interacting protein (FNIP)-1 or FNIP2 and further regulated by ULK1. As observed by elevation of GABARAP, sequestome 1 (SQSTM1) and microtubule-associated protein 1 light chain 3 (MAP1LC3B) in chromophobe and clear cell tumors from a BHD patient, we found that autophagy is impaired in BHD-associated renal tumors. Consequently, this work reveals a novel facet of autophagy regulation by ULK1 and substantially contributes to our understanding of FLCN function by linking it directly to autophagy through GABARAP and ULK1. PMID- 25126727 TI - Autophagy in microglia degrades extracellular beta-amyloid fibrils and regulates the NLRP3 inflammasome. AB - Accumulation of beta-amyloid (Abeta) and resultant inflammation are critical pathological features of Alzheimer disease (AD). Microglia, a primary immune cell in brain, ingests and degrades extracellular Abeta fibrils via the lysosomal system. Autophagy is a catabolic process that degrades native cellular components, however, the role of autophagy in Abeta degradation by microglia and its effects on AD are unknown. Here we demonstrate a novel role for autophagy in the clearance of extracellular Abeta fibrils by microglia and in the regulation of the Abeta-induced NLRP3 (NLR family, pyrin domain containing 3) inflammasome using microglia specific atg7 knockout mice and cell cultures. We found in microglial cultures that Abeta interacts with MAP1LC3B-II via OPTN/optineurin and is degraded by an autophagic process mediated by the PRKAA1 pathway. We anticipate that enhancing microglial autophagy may be a promising new therapeutic strategy for AD. PMID- 25126731 TI - Correlative light and electron microscopy imaging of autophagy in a zebrafish infection model. AB - High-resolution imaging of autophagy has been used intensively in cell culture studies, but so far it has been difficult to visualize this process in detail in whole animal models. In this study we present a versatile method for high resolution imaging of microbial infection in zebrafish larvae by injecting pathogens into the tail fin. This allows visualization of autophagic compartments by light and electron microscopy, which makes it possible to correlate images acquired by the 2 techniques. Using this method we have studied the autophagy response against Mycobacterium marinum infection. We show that mycobacteria during the progress of infection are frequently associated with GFP-Lc3-positive vesicles, and that 2 types of GFP-Lc3-positive vesicles were observed. The majority of these vesicles were approximately 1 MUm in size and in close vicinity of bacteria, and a smaller number of GFP-Lc3-positive vesicles was larger in size and were observed to contain bacteria. Quantitative data showed that these larger vesicles occurred significantly more in leukocytes than in other cell types, and that approximately 70% of these vesicles were positive for a lysosomal marker. Using electron microscopy, it was found that approximately 5% of intracellular bacteria were present in autophagic vacuoles and that the remaining intracellular bacteria were present in phagosomes, lysosomes, free inside the cytoplasm or occurred as large aggregates. Based on correlation of light and electron microscopy images, it was shown that GFP-Lc3-positive vesicles displayed autophagic morphology. This study provides a new approach for injection of pathogens into the tail fin, which allows combined light and electron microscopy imaging in vivo and opens new research directions for studying autophagy process related to infectious diseases. PMID- 25126732 TI - Autophagy is required for G1/G0 quiescence in response to nitrogen starvation in Saccharomyces cerevisiae. AB - In response to starvation, cells undergo increased levels of autophagy and cell cycle arrest but the role of autophagy in starvation-induced cell cycle arrest is not fully understood. Here we show that autophagy genes regulate cell cycle arrest in the budding yeast Saccharomyces cerevisiae during nitrogen starvation. While exponentially growing wild-type yeasts preferentially arrest in G1/G0 in response to starvation, yeasts carrying null mutations in autophagy genes show a significantly higher percentage of cells in G2/M. In these autophagy-deficient yeast strains, starvation elicits physiological properties associated with quiescence, such as Snf1 activation, glycogen and trehalose accumulation as well as heat-shock resistance. However, while nutrient-starved wild-type yeasts finish the G2/M transition and arrest in G1/G 00 autophagy-deficient yeasts arrest in telophase. Our results suggest that autophagy is crucial for mitotic exit during starvation and appropriate entry into a G1/G0 quiescent state. PMID- 25126735 TI - A mitochondrial-associated link between an effector caspase and autophagic flux. AB - It has become evident that caspases function in nonapoptotic cellular processes in addition to the canonical role for caspases in apoptotic cell death. We recently demonstrated that the Drosophila effector caspase Dcp-1 localizes to the mitochondria and positively regulates starvation-induced autophagic flux during mid-oogenesis. Loss of Dcp-1 leads to elongation of the mitochondrial network, increased levels of the adenine nucleotide translocase sesB, increased ATP levels, and a reduction in autophagy. We found that sesB is a negative regulator of autophagic flux, and Dcp-1 interacts with sesB in a nonproteolytic manner to regulate its stability, uncovering a novel mechanism of mitochondrial associated, caspase-mediated regulation of autophagy in vivo. PMID- 25126734 TI - Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects against transient ischemic brain injury: Involvement of PARK2-dependent mitophagy. AB - Transient cerebral ischemia leads to endoplasmic reticulum (ER) stress. However, the contributions of ER stress to cerebral ischemia are not clear. To address this issue, the ER stress activators tunicamycin (TM) and thapsigargin (TG) were administered to transient middle cerebral artery occluded (tMCAO) mice and oxygen glucose deprivation-reperfusion (OGD-Rep.)-treated neurons. Both TM and TG showed significant protection against ischemia-induced brain injury, as revealed by reduced brain infarct volume and increased glucose uptake rate in ischemic tissue. In OGD-Rep.-treated neurons, 4-PBA, the ER stress releasing mechanism, counteracted the neuronal protection of TM and TG, which also supports a protective role of ER stress in transient brain ischemia. Knocking down the ER stress sensor Eif2s1, which is further activated by TM and TG, reduced the OGD Rep.-induced neuronal cell death. In addition, both TM and TG prevented PARK2 loss, promoted its recruitment to mitochondria, and activated mitophagy during reperfusion after ischemia. The neuroprotection of TM and TG was reversed by autophagy inhibition (3-methyladenine and Atg7 knockdown) as well as Park2 silencing. The neuroprotection was also diminished in Park2(+/-) mice. Moreover, Eif2s1 and downstream Atf4 silencing reduced PARK2 expression, impaired mitophagy induction, and counteracted the neuroprotection. Taken together, the present investigation demonstrates that the ER stress induced by TM and TG protects against the transient ischemic brain injury. The PARK2-mediated mitophagy may be underlying the protection of ER stress. These findings may provide a new strategy to rescue ischemic brains by inducing mitophagy through ER stress activation. PMID- 25126736 TI - Autophagy deficiency stabilizes TWIST1 to promote epithelial-mesenchymal transition. AB - The transcription factor TWIST1 is a basic helix-loop-helix protein that regulates epithelial-mesenchymal transition (EMT) in early embryonic morphogenesis, cancer development, and cancer metastasis. The regulation of TWIST1 remains poorly understood. Recently, we found that autophagy deficiency stabilizes TWIST1 protein through SQSTM1/p62 accumulation. SQSTM1 binds with TWIST1 to inhibit TWIST1 degradation in both autophagosomes and proteasomes. SQSTM1-mediated TWIST1 stabilization promotes EMT in vitro, and tumor growth and metastasis in mice. We propose autophagy as a new mechanism to control the TWIST1 protein levels and activity in cancer development and progression. PMID- 25126737 TI - HMGB1-dependent and -independent autophagy. AB - HMGB1 (high mobility group box 1) is a multifunctional, ubiquitous protein located inside and outside cells that plays a critical role in various physiological and pathological processes including cell development, differentiation, inflammation, immunity, metastasis, metabolism, and death. Increasing evidence demonstrates that HMGB1-dependent autophagy promotes chemotherapy resistance, sustains tumor metabolism requirements and T cell survival, prevents polyglutamine aggregates and excitotoxicity, and protects against endotoxemia, bacterial infection, and ischemia-reperfusion injury in vitro or in vivo. In contrast, HMGB1 may not be required for autophagy in some organs such as the liver and heart. Understanding HMGB1-dependent and independent autophagy in more detail will provide insight into the integrated stress response and guide HMGB1-based therapeutic intervention. PMID- 25126738 TI - Positive doping results caused by the single-dose local injection of triamcinolone acetonide. AB - Triamcinolone acetonide (TA) is classified as an S9 glucocorticoid in the 2014 Prohibited List published by the World Anti-Doping Agency, which caused it to be prohibited in-competition when administered orally, intravenously, intramuscularly or rectally. The Minimum Required Performance Level (MRPL) for the detection and identification of glucocorticoids is 30 ng/mL. Other common local injection routes, such as intraarticular, intratendinous, or intrabursal injection, are not prohibited. The purpose of this study was to analyze the TA and triamcinolone (T) concentrations in urine after a single injection of TA in patients to determine if it would produce a positive result. This study was performed on 40 patients with sports injuries or joint pains. TA was administered locally (doses varied from 12 to 80 mg). Samples were extracted using a solid phase extraction column, followed by hydrolysis and liquid extraction using diethyl ether. The elution solvents were collected and dried. The dried residue was reconstituted and assayed by performing liquid chromatography-tandem mass spectrometry (LC-MS/MS) in positive ionization mode using electrospray ionization and multiple-reaction monitoring as the acquisition mode. The results demonstrated that the concentrations of both TA and T in urine exceeded the MRPL (30 ng/mL) after a single local injection. We obtained positive results for TA in 25 patients, and a positive result for T in one patient. Furthermore, the metabolic situation of TA, a long-acting glucocorticoid, was not an exact linear model. The highest concentrations of TA and T appeared 1-4h after injection. This information could be useful for limiting the misuse of TA by athletes. We suggest that athletes be aware when using TA injections during a competition period and obtain approval for therapeutic use exemption prior to using TA. PMID- 25126739 TI - Factors affecting human milk composition. PMID- 25126740 TI - Toll-like receptor 9 mediated responses in cardiac fibroblasts. AB - Altered cardiac Toll-like receptor 9 (TLR9) signaling is important in several experimental cardiovascular disorders. These studies have predominantly focused on cardiac myocytes or the heart as a whole. Cardiac fibroblasts have recently been attributed increasing significance in mediating inflammatory signaling. However, putative TLR9-signaling through cardiac fibroblasts remains non investigated. Thus, our aim was to explore TLR9-signaling in cardiac fibroblasts and investigate the consequence of such receptor activity on classical cardiac fibroblast cellular functions. Cultivated murine cardiac fibroblasts were stimulated with different TLR9 agonists (CpG A, B and C) and assayed for the secretion of inflammatory cytokines (tumor necrosis factor alpha [TNFalpha], CXCL2 and interferon alpha/beta). Expression of functional cardiac fibroblast TLR9 was proven as stimulation with CpG B and -C caused significant CXCL2 and TNFalpha-release. These responses were TLR9-specific as complete inhibition of receptor-stimulated responses was achieved by co-treatment with a TLR9-antagonist (ODN 2088) or chloroquine diphosphate. TLR9-stimulated responses were also found more potent in cardiac fibroblasts when compared with classical innate immune cells. Stimulation of cardiac fibroblasts TLR9 was also found to attenuate migration and proliferation, but did not influence myofibroblast differentiation in vitro. Finally, results from in vivo TLR9-stimulation with subsequent fractionation of specific cardiac cell-types (cardiac myocytes, CD45+ cells, CD31+ cells and cardiac fibroblast-enriched cell-fractions) corroborated our in vitro data and provided evidence of differentiated cell-specific cardiac responses. Thus, we conclude that cardiac fibroblast may constitute a significant TLR9 responder cell within the myocardium and, further, that such receptor activity may impact important cardiac fibroblast cellular functions. PMID- 25126742 TI - Single Si nanowire (diameter <= 100 nm) based polarization sensitive near infrared photodetector with ultra-high responsivity. AB - We report the fabrication and optical response of boron-doped single silicon nanowire-based metal-semiconductor-metal photodetector. Typical single nanowire devices with diameter of ~80-100 nm and electrode spacing of ~1 MUm were made using electron-beam lithography from nanowires, grown by a metal-assisted chemical etching process. A high responsivity, of the order of 10(4) A W(-1), was observed even at zero bias in a single nanowire photodetector with peak responsivity in the near-infrared region. The responsivity was found to increase with increasing bias and decreasing nanowire diameter. Finite element based optical simulation was proposed to explain the diameter dependent performance of a single nanowire. The observed photoresponse is sensitive to the polarization of exciting light source, allowing the device to act as a polarization-dependent near-infrared photodetector. PMID- 25126741 TI - Clinical outcomes of penetrating keratoplasty performed with the VisuMax femtosecond laser system and comparison with conventional penetrating keratoplasty. AB - PURPOSE: To assess the clinical outcomes of femtosecond laser-assisted keratoplasty (FLAK) using the VisuMax femtosecond laser system, and to compare them with those of conventional penetrating keratoplasty (PK). METHODS: We retrospectively examined 20 eyes of 20 consecutive patients undergoing FLAK and 20 eyes of 20 age- and diagnosis-matched patients undergoing conventional PK. We quantitatively assessed corneal astigmatism, refractive astigmatism, and corrected visual acuity, 1, 3, and 6 months postoperatively, and endothelial cell density 6 months postoperatively. RESULTS: Corneal and refractive astigmatism after FLAK were significantly lower after FLAK than that after conventional PK at 3 and 6 months postoperatively (p = 0.04 and p = 0.03, respectively, Mann-Whitney U test). FLAK provided significantly faster visual recovery than conventional PK at 1 month postoperatively (p = 0.02), but not at 3 and 6 months postoperatively (p = 0.52 and p = 0.80, respectively). We found no significant differences in the change in endothelial cell density between the two groups (p = 0.30). CONCLUSIONS: FLAK using the VisuMax femtosecond laser system induces significantly less corneal and refractive astigmatism than conventional PK, and provides significantly faster visual recovery in the early postoperative period, possibly because the geometry of the donor-recipient matching is more physiological and requires less tight sutures. It is suggested that FLAK has advantages over conventional PK, in terms of astigmatism and fast visual recovery. PMID- 25126743 TI - Epigenetic inactivation of inositol polyphosphate 4-phosphatase B (INPP4B), a regulator of PI3K/AKT signaling pathway in EBV-associated nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is a common viral-associated neoplasm in which multiple signaling cascades are interfered with by Epstein-Bar virus (EBV) latent proteins and various genetic alterations. Aside from the previously reported PIK3CA amplification, we examined the role of INPP4B, a negative regulator of the PI3K/AKT signaling pathway in the development of NPC. By RT-PCR and Western blotting, we revealed that the expression of INPP4B was down-regulated in all five established EBV-positive tumor lines. While INPP4B was consistently expressed in normal nasopharyngeal epithelial cells, downregulation of INPP4B was found in 32/65 (49.2%) of primary tumors by immunohistochemistry. Furthermore, our study also demonstrated the hypermethylation of the 5'CpG island of INPP4B in the tumors in which INPP4B transcription was downregulated. Notably, the re expression of INPP4B was detected in the NPC cells treated with the demethylation agent (5-aza-2'deoxycytidine). Our study showed that promoter hypermethylation was the major mechanism for transcriptional silencing of INPP4B in NPC. Furthermore, restoration of INPP4B expression significantly suppressed PI3K/AKT downstream signals in the NPC C666-1 cells. In vivo growth inhibition was clearly demonstrated in the tumor cells stably expressing INPP4B. The findings indicate that epigenetic inactivation of INPP4B is one of the key mechanisms in activating PI3K/AKT signaling cascade and playing a role in the tumorigenesis of NPC. PMID- 25126744 TI - De novo assembly of the perennial ryegrass transcriptome using an RNA-Seq strategy. AB - BACKGROUND: Perennial ryegrass is a highly heterozygous outbreeding grass species used for turf and forage production. Heterozygosity can affect de-Bruijn graph assembly making de novo transcriptome assembly of species such as perennial ryegrass challenging. Creating a reference transcriptome from a homozygous perennial ryegrass genotype can circumvent the challenge of heterozygosity. The goals of this study were to perform RNA-sequencing on multiple tissues from a highly inbred genotype to develop a reference transcriptome. This was complemented with RNA-sequencing of a highly heterozygous genotype for SNP calling. RESULT: De novo transcriptome assembly of the inbred genotype created 185,833 transcripts with an average length of 830 base pairs. Within the inbred reference transcriptome 78,560 predicted open reading frames were found of which 24,434 were predicted as complete. Functional annotation found 50,890 transcripts with a BLASTp hit from the Swiss-Prot non-redundant database, 58,941 transcripts with a Pfam protein domain and 1,151 transcripts encoding putative secreted peptides. To evaluate the reference transcriptome we targeted the high-affinity K+ transporter gene family and found multiple orthologs. Using the longest unique open reading frames as the reference sequence, 64,242 single nucleotide polymorphisms were found. One thousand sixty one open reading frames from the inbred genotype contained heterozygous sites, confirming the high degree of homozygosity. CONCLUSION: Our study has developed an annotated, comprehensive transcriptome reference for perennial ryegrass that can aid in determining genetic variation, expression analysis, genome annotation, and gene mapping. PMID- 25126745 TI - T cell IFN-gamma suppression following alcohol and burn injury is independent of miRNA155. AB - miRNA155 has been implicated in normal T cell function and their differentiations into the Th1 subtype. We have shown that acute alcohol (ethanol) intoxication combined with burn injury suppresses T cell IFN-gamma release. Herein, we examined whether the decrease in IFN-gamma is resulted from altered expression of miRNA155 and transcription factors--NFAT, Tbx21, Jun and Fos--in T cells following ethanol and burn injury. Mice received ethanol (~3 g/Kg) 4 hours prior to ~12.5% total body surface area sham or burn injury and were sacrificed one day after injury. Splenic T cells were harvested and cultured with anti-CD3 (2 ug/ml) in the presence or absence of rIL-12 (10 ng/ml) or PMA (10 ng/ml) plus ionomycin (50 ng/ml) for 48 hours. We observed a significant decrease in miRNA155, NFAT, Tbx21, Jun and Fos expression as well as IFN-gamma release in T cells cultured with anti-CD3 following ethanol and burn injury compared with shams. The co treatment of T cells with rIL-12 prevented the decrease in IFN-gamma and NFAT, Tbx21, Jun and Fos, but not miRNA155. In contrast, the co-treatment with PMA plus ionomycin normalized the expression of NFAT. It did not prevent the decrease in IFN-gamma, Tbx21, Jun, Fos and miRNA155. Finally, results obtained in miRNA155-/- mice did not show any change in T cell release of IFN-gamma or expression of nuclear factors compared to wildtype mice. Together, these findings suggest that while ethanol and burn injury decreases the expression of miRNA155, it may not be involved in decreased IFN-gamma under those conditions. PMID- 25126746 TI - Do cells contribute to tendon and ligament biomechanics? AB - INTRODUCTION: Acellular scaffolds are increasingly used for the surgical repair of tendon injury and ligament tears. Despite this increased use, very little data exist directly comparing acellular scaffolds and their native counterparts. Such a comparison would help establish the effectiveness of the acellularization procedure of human tissues. Furthermore, such a comparison would help estimate the influence of cells in ligament and tendon stability and give insight into the effects of acellularization on collagen. MATERIAL AND METHODS: Eighteen human iliotibial tract samples were obtained from nine body donors. Nine samples were acellularized with sodium dodecyl sulphate (SDS), while nine counterparts from the same donors remained in the native condition. The ends of all samples were plastinated to minimize material slippage. Their water content was adjusted to 69%, using the osmotic stress technique to exclude water content-related alterations of the mechanical properties. Uniaxial tensile testing was performed to obtain the elastic modulus, ultimate stress and maximum strain. The effectiveness of the acellularization procedure was histologically verified by means of a DNA assay. RESULTS: The histology samples showed a complete removal of the cells, an extensive, yet incomplete removal of the DNA content and alterations to the extracellular collagen. Tensile properties of the tract samples such as elastic modulus and ultimate stress were unaffected by acellularization with the exception of maximum strain. DISCUSSION: The data indicate that cells influence the mechanical properties of ligaments and tendons in vitro to a negligible extent. Moreover, acellularization with SDS alters material properties to a minor extent, indicating that this method provides a biomechanical match in ligament and tendon reconstruction. However, the given protocol insufficiently removes DNA. This may increase the potential for transplant rejection when acellular tract scaffolds are used in soft tissue repair. Further research will help optimize the SDS-protocol for clinical application. PMID- 25126747 TI - Increased expression of CCN2, epithelial membrane antigen, and fibroblast activation protein in hepatocellular carcinoma with fibrous stroma showing aggressive behavior. AB - Tumor behavior is affected by the tumor microenvironment, composed of cancer associated fibroblasts (CAFs). Meanwhile, hepatocellular carcinomas (HCC) with fibrous stroma reportedly exhibit aggressive behavior suggestive of tumor-stroma interaction. However, evidence of the crosstalk remains unclear. In this study, CCN2, epithelial membrane antigen (EMA), fibroblast activation protein (FAP), and keratin 19 (K19) expression was studied in 314 HCCs (cohort 1), 42 scirrhous HCCs (cohort 2), and 36 chronic hepatitis/cirrhosis specimens by immunohistochemistry. Clinicopathological parameters were analyzed according to the expressions of these markers. In tumor epithelial cells from cohort 1, CCN2 and EMA were expressed in 15.3% and 17.2%, respectively, and their expressions were more frequent in HCCs with fibrous stroma (>=5% of tumor area) than those without (P<0.05 for all); CCN2 expression was well correlated with K19 and EMA expression. In tumor stromal cells, FAP expression was found in 6.7%. In cohort 2, CCN2, EMA, and FAP expression was noted in 40.5%, 40.5%, and 66.7%, respectively, which was more frequent than that in cohort 1 (P<0.05 for all). Additionally, EMA expression was associated with the expression of K19, CCN2, and FAP (P<0.05 for all); EMA expressing tumor epithelial cells showed a topographic closeness to FAP-expressing CAFs. Analysis of disease-free survival revealed CCN2 expression to be a worse prognostic factor in both cohort 1 (P = 0.005) and cohort 2 (P = 0.023), as well as EMA as a worse prognostic factor in cohort 2 (P = 0.048). In conclusion, expression of CCN2, EMA, and FAP may be involved in the activation of CAFs in HCC, giving rise to aggressive behavior. Significant correlation between EMA-expressing tumor cells and FAP-expressing CAFs and their topographic closeness suggests possible cross-talk between tumor epithelial cells and stromal cells in the tumor microenvironment of HCC. PMID- 25126749 TI - MafA is required for postnatal proliferation of pancreatic beta-cells. AB - The postnatal proliferation and maturation of insulin-secreting pancreatic beta cells are critical for glucose metabolism and disease development in adults. Elucidation of the molecular mechanisms underlying these events will be beneficial to direct the differentiation of stem cells into functional beta cells. Maturation of beta-cells is accompanied by increased expression of MafA, an insulin gene transcription factor. Transcriptome analysis of MafA knockout islets revealed MafA is required for the expression of several molecules critical for beta-cell function, including Glut2, ZnT8, Granuphilin, Vdr, Pcsk1 and Urocortin 3, as well as Prolactin receptor (Prlr) and its downstream target Cyclin D2 (Ccnd2). Inhibition of MafA expression in mouse islets or beta-cell lines resulted in reduced expression of Prlr and Ccnd2, and MafA transactivated the Prlr promoter. Stimulation of beta-cells by prolactin resulted in the phosphorylation and translocation of Stat5B and an increased nuclear pool of Ccnd2 via Prlr and Jak2. Consistent with these results, the loss of MafA resulted in impaired proliferation of beta-cells at 4 weeks of age. These results suggest that MafA regulates the postnatal proliferation of beta-cells via prolactin signaling. PMID- 25126752 TI - Attentional cueing by cross-modal congruency produces both facilitation and inhibition on short-term visual recognition. AB - The attentional modulation of performance in a memory task, comparable to the one obtained in a perceptual task, is at the focus of contemporary research. We hypothesized that a biphasic effect (namely, facilitation followed by inhibition) can be obtained in visual working memory when attention is cued towards one item of the memorandum and participants must recognize a delayed probe as being identical to any item of the memorandum. In every trial, a delayed spiky/curvy probe appeared centrally, to be matched with the same-category shape maintained in visual working memory which could be either physically identical (positive trials) or only categorically similar (negative trials). To orient the participant's attention towards a selected portion of a two-item memorandum, a (tzk/wow) sound was played simultaneously with two lateral visual shapes (one spiky and one curved). Our results indicate that an exogenous attentional shift during perception of the memorandum, induced by a congruent audio-visual pairing, first facilitates and then inhibits the recognition of a cued item (but not of a non-cued item) stored in visual working memory. A coherent pattern of individual differences emerged, indicating that the amount of early facilitation in congruent-sound trials was negatively correlated with recognition sensitivity in no-sound trials (suggesting that the inverse effectiveness rule may also apply to memory) and positively correlated with later inhibition, as well as with the self reported susceptibility to memory failures. PMID- 25126753 TI - A correlative approach to segmenting phases and ferrite morphologies in transformation-induced plasticity steel using electron back-scattering diffraction and energy dispersive X-ray spectroscopy. AB - Using a combination of electron back-scattering diffraction and energy dispersive X-ray spectroscopy data, a segmentation procedure was developed to comprehensively distinguish austenite, martensite, polygonal ferrite, ferrite in granular bainite and bainitic ferrite laths in a thermo-mechanically processed low-Si, high-Al transformation-induced plasticity steel. The efficacy of the ferrite morphologies segmentation procedure was verified by transmission electron microscopy. The variation in carbon content between the ferrite in granular bainite and bainitic ferrite laths was explained on the basis of carbon partitioning during their growth. PMID- 25126750 TI - Inhibition of HMGB1-induced angiogenesis by cilostazol via SIRT1 activation in synovial fibroblasts from rheumatoid arthritis. AB - High mobility group box chromosomal protein 1 (HMGB-1) released from injured cells plays an important role in the development of arthritis. This study investigated the anti-angiogenic effects of cilostazol in collagen-induced arthritis (CIA) of mice, and the underlying mechanisms involved. The expressions of HIF-1alpha, VEGF, NF-kappaB p65 and SIRT1 in synovial fibroblasts obtained from rheumatoid arthritis (RA) patients were assessed by Western blotting, and in vitro and in vivo angiogenesis were analyzed. Tube formations by human microvascular endothelial cells (HMVECs) were significantly increased by direct exposure to HMGB1 or to conditioned medium derived from HMGB1-stimulated RA fibroblasts, and these increases were attenuated by cilostazol, the latter of which was blocked by sirtinol. HMGB1 increased the expression of HIF-1alpha and VEGF and concomitantly increased nuclear NF-kappaB p65 and DNA binding activity, but these effects of HMGB1 were inhibited by cilostazol. SIRT1 protein expression was time-dependently decreased (3-24 hr) by HMGB1, which was recovered by pretreatment with cilostazol (1-30 uM) or resveratrol, accompanying with increased SIRT1 deacetylase activity. In the tibiotarsal joint tissues of CIA mice treated with vehicle, HIF-1alpha- and VEGF-positive spots and CD31 staining were markedly exaggerated, whereas SIRT1 immunofluorescence was diminished. These variables were wholly reversed in cilostazol (30 mg/kg/day)-treated mice. Furthermore, number of blood vessels stained by von Willebrand factor antibody was significantly lower in cilostazol-treated CIA mice. Summarizing, cilostazol activated SIRT1 and inhibited NF-kappaB-mediated transcription, thereby suppressing the expression of HIF-1alpha and VEGF. In addition, cilostazol caused HIF-1alpha deacetylation by enhancing SIRT1 activity and reduced VEGF production, thereby had an anti-angiogenic effect in vitro studies and in CIA murine model. PMID- 25126755 TI - Overview of research on the mental health impact of violence in the Middle East in light of the Arab Spring. AB - This is a baseline of published research in the trauma field by Arab researchers. It highlights groundbreaking attempts by Arab researchers to investigate the mental health impact of violence in their countries before the Arab Spring. Peer reviewed articles (N = 157) were identified through computerized searches in PubMed, PsycINFO, Google Scholar, and Pilots Database, 1995 to 2012. A synopsis of the published research included (a) country, (b) screening instruments, (c) sample size, (d) methods, and (e) results. The findings reveal that domestic violence attracted most attention after civil strife in Palestine and Lebanon. Torture survivors and victims of sexual violence received little attention. Study instruments were borrowed from Western researchers without being validated within local Arab cultures. No clinical outcome studies were found. In light of the Arab Spring, it is urgent that Arab researchers conduct studies that are evidence based and culturally valid addressing the mental health care of all traumatized citizens. PMID- 25126754 TI - Prevalence and predictors of mental disorders in intentionally and unintentionally injured emergency center patients. AB - Little is known about the prevalence and predictors of mental disorders among injured emergency center (EC) patients in low- and middle-income countries (LMICs). Patients presenting with either an intentional or unintentional injury were recruited (N = 200). Mental health, injury, and psychological trauma histories were assessed. Descriptive statistics and logistic regressions were conducted, and predictors of current mental disorder were identified. Diagnostic criteria for a current mental disorder, including substance use disorders, were met by 59.5% of the participants. Compared with those with an unintentional injury, the intentionally injured participants were more likely to be diagnosed with a current mental disorder (66.9% vs. 48.8%, p = .01). High frequencies of previous intentional injuries predicted for current mental disorder (OR = 1.46, 95% CI 1.08-1.98), whereas male gender and witnessed community violence predicted substance use disorder diagnoses. The findings indicate that injured EC patients, particularly those with intentional injuries, are at risk for mental disorders. Psychosocial interventions in the EC context can potentially make an important contribution in reducing the burden of mental disorders and injuries in LMICs. PMID- 25126756 TI - Aquatic metagenomes implicate Thaumarchaeota in global cobalamin production. AB - Cobalamin (vitamin B12) is a complex metabolite and essential cofactor required by many branches of life, including most eukaryotic phytoplankton. Algae and other cobalamin auxotrophs rely on environmental cobalamin supplied from a relatively small set of cobalamin-producing prokaryotic taxa. Although several Bacteria have been implicated in cobalamin biosynthesis and associated with algal symbiosis, the involvement of Archaea in cobalamin production is poorly understood, especially with respect to the Thaumarchaeota. Based on the detection of cobalamin synthesis genes in available thaumarchaeotal genomes, we hypothesized that Thaumarchaeota, which are ubiquitous and abundant in aquatic environments, have an important role in cobalamin biosynthesis within global aquatic ecosystems. To test this hypothesis, we examined cobalamin synthesis genes across sequenced thaumarchaeotal genomes and 430 metagenomes from a diverse range of marine, freshwater and hypersaline environments. Our analysis demonstrates that all available thaumarchaeotal genomes possess cobalamin synthesis genes, predominantly from the anaerobic pathway, suggesting widespread genetic capacity for cobalamin synthesis. Furthermore, although bacterial cobalamin genes dominated most surface marine metagenomes, thaumarchaeotal cobalamin genes dominated metagenomes from polar marine environments, increased with depth in marine water columns, and displayed seasonality, with increased winter abundance observed in time-series datasets (e.g., L4 surface water in the English Channel). Our results also suggest niche partitioning between thaumarchaeotal and cyanobacterial ribosomal and cobalamin synthesis genes across all metagenomic datasets analyzed. These results provide strong evidence for specific biogeographical distributions of thaumarchaeotal cobalamin genes, expanding our understanding of the global biogeochemical roles played by Thaumarchaeota in aquatic environments. PMID- 25126757 TI - Viruses accumulate in aging infection centers of a fungal forest pathogen. AB - Fungal viruses (mycoviruses) with RNA genomes are believed to lack extracellular infective particles. These viruses are transmitted laterally among fungal strains through mycelial anastomoses or vertically via their infected spores, but little is known regarding their prevalence and patterns of dispersal under natural conditions. Here, we examined, in detail, the spatial and temporal changes in a mycovirus community and its host fungus Heterobasidion parviporum, the most devastating fungal pathogen of conifers in the Boreal forest region. During the 7 year sampling period, viruses accumulated in clonal host individuals as a result of indigenous viruses spreading within and between clones as well as novel strains arriving via airborne spores. Viral community changes produced pockets of heterogeneity within large H. parviporum clones. The appearance of novel viral infections in aging clones indicated that transient cell-to-cell contacts between Heterobasidion strains are likely to occur more frequently than what was inferred from genotypic analyses. Intraspecific variation was low among the three partitivirus species at the study site, whereas the unassigned viral species HetRV6 was highly polymorphic. The accumulation of point mutations during persistent infections resulted in viral diversification, that is, the presence of nearly identical viral sequence variants within single clones. Our results also suggest that co-infections by distantly related viral species are more stable than those between conspecific strains, and mutual exclusion may play a role in determining mycoviral communities. PMID- 25126758 TI - Disturbance and temporal partitioning of the activated sludge metacommunity. AB - The resilience of microbial communities to press disturbances and whether ecosystem function is governed by microbial composition or by the environment have not been empirically tested. To address these issues, a whole-ecosystem manipulation was performed in a full-scale activated sludge wastewater treatment plant. The parameter solids retention time (SRT) was used to manipulate microbial composition, which started at 30 days, then decreased to 12 and 3 days, before operation was restored to starting conditions (30-day SRT). Activated sludge samples were collected throughout the 313-day time series in parallel with bioreactor performance ('ecosystem function'). Bacterial small subunit (SSU) rRNA genes were surveyed from sludge samples resulting in a sequence library of >417,000 SSU rRNA genes. A shift in community composition was observed for 12- and 3-day SRTs. The composition was altered such that r-strategists were enriched in the system during the 3-day SRT, whereas K-strategists were only present at SRTs?12 days. This shift corresponded to loss of ecosystem functions (nitrification, denitrification and biological phosphorus removal) for SRTs?12 days. Upon return to a 30-day SRT, complete recovery of the bioreactor performance was observed after 54 days despite an incomplete recovery of bacterial diversity. In addition, a different, yet phylogenetically related, community with fewer of its original rare members displaced the pre-disturbance community. Our results support the hypothesis that microbial ecosystems harbor functionally redundant phylotypes with regard to general ecosystem functions (carbon oxidation, nitrification, denitrification and phosphorus accumulation). However, the impacts of decreased rare phylotype membership on ecosystem stability and micropollutant removal remain unknown. PMID- 25126759 TI - Aqueous leaf extract of Jatropha gossypiifolia L. (Euphorbiaceae) inhibits enzymatic and biological actions of Bothrops jararaca snake venom. AB - Snakebites are a serious public health problem due their high morbi-mortality. The main available specific treatment is the antivenom serum therapy, which has some disadvantages, such as poor neutralization of local effects, risk of immunological reactions, high cost and difficult access in some regions. In this context, the search for alternative therapies is relevant. Therefore, the aim of this study was to evaluate the antiophidic properties of Jatropha gossypiifolia, a medicinal plant used in folk medicine to treat snakebites. The aqueous leaf extract of the plant was prepared by decoction and phytochemical analysis revealed the presence of sugars, alkaloids, flavonoids, tannins, terpenes and/or steroids and proteins. The extract was able to inhibit enzymatic and biologic activities induced by Bothrops jararaca snake venom in vitro and in vivo. The blood incoagulability was efficiently inhibited by the extract by oral route. The hemorrhagic and edematogenic local effects were also inhibited, the former by up to 56% and the latter by 100%, in animals treated with extract by oral and intraperitoneal routes, respectively. The inhibition of myotoxic action of B. jararaca reached almost 100%. According to enzymatic tests performed, it is possible to suggest that the antiophidic activity may be due an inhibitory action upon snake venom metalloproteinases (SVMPs) and/or serine proteinases (SVSPs), including fibrinogenolytic enzymes, clotting factors activators and thrombin like enzymes (SVTLEs), as well upon catalytically inactive phospholipases A2 (Lys49 PLA2). Anti-inflammatory activity, at least partially, could also be related to the inhibition of local effects. Additionally, protein precipitating and antioxidant activities may also be important features contributing to the activity presented. In conclusion, the results demonstrate the potential antiophidic activity of J. gossypiifolia extract, including its significant action upon local effects, suggesting that it may be used as a new source of bioactive molecules against bothropic venom. PMID- 25126760 TI - Targeted disruption of the intracellular domain of receptor FgfrL1 in mice. AB - FgfrL1 is the fifth member of the fibroblast growth factor receptor (Fgfr) family. Studies with FgfrL1 deficient mice have demonstrated that the gene plays an important role during embryonic development. FgfrL1 knock-out mice die at birth as they have a malformed diaphragm and lack metanephric kidneys. Similar to the classical Fgfrs, the FgfrL1 protein contains an extracellular part composed of three Ig-like domains that interact with Fgf ligands and heparin. However, the intracellular part of FgfrL1 is not related to the classical receptors and does not possess any tyrosine kinase activity. Curiously enough, the amino acid sequence of this domain is barely conserved among different species, with the exception of three motifs, namely a dileucine peptide, a tandem tyrosine-based motif YXXPhi and a histidine-rich sequence. To investigate the function of the intracellular domain of FgfrL1, we have prepared genetically modified mice that lack the three conserved sequence motifs, but instead contain a GFP cassette (FgfrL1DeltaC-GFP). To our surprise, homozygous FgfrL1DeltaC-GFP knock-in mice are viable, fertile and phenotypically normal. They do not exhibit any alterations in the diaphragm or the kidney, except for a slight reduction in the number of glomeruli that does not appear to affect life expectancy. In addition, the pancreas of both FgfrL1DeltaC-GFP knock-in and FgfrL1 knock-out mice do not show any disturbances in the production of insulin, in contrast to what has been suggested by recent studies. Thus, the conserved motifs of the intracellular FgfrL1 domain are dispensable for organogenesis and normal life. We conclude that the extracellular domain of the protein must conduct the vital functions of FgfrL1. PMID- 25126762 TI - Malignant self-regard: a self-structure enhancing the understanding of masochistic, depressive, and vulnerably narcissistic personalities. AB - Several personality disorders have been prominent in the clinical literature but have been inadequately recognized in the diagnostic manuals. This group includes masochistic, self-defeating, depressive, and vulnerably narcissistic personality disorders. The theoretical and empirical relationship of these disorders is reviewed. It is proposed that the construct of malignant self-regard may account for the similarities among them. The construct describes these personality types as being fundamentally related through problematic manifestations of self structure. The article discusses the diagnostic value of such a construct and the implications of a psychodynamically informed framework for classifying personality pathology. PMID- 25126763 TI - Disordered self in the schizophrenia spectrum: a clinical and research perspective. AB - This article explores the phenomenological and empirical rediscovery of anomalous self-experience as a core feature of the schizophrenia spectrum disorders and presents the current status of research in this field. Historically, a disordered self was considered to be a constitutive phenotype of schizophrenia. Although the notion of a disordered self has continued to appear occasionally over the years mainly in the phenomenologically or psychodynamically oriented literature-this notion was usually considered as a theoretical construct rather than as referring to concretely lived anomalous experiences. Empirical research on the disorders of self-experience in schizophrenia can be traced back to the US-Denmark psychopathological collaboration in the well-known adoption and high-risk studies, which aimed at identifying trait or phenotypic vulnerability features. This research was later followed by clinical work with first-admission schizophrenia patients. We offer clinical descriptions of anomalous self experience and outline the phenomenological structures of subjectivity that are needed for grasping the nature of these anomalous experiential phenomena. What appears to underlie these experiences is an instability of the first-person perspective that threatens the basic experience of being a self-coinciding, embodied, demarcated, and persisting subject of awareness. We summarize a series of empirical studies targeting self-experience in schizophrenia performed prior to and after the construction of a phenomenologically oriented psychometric instrument for assessing anomalies of self-experience, the Examination of Anomalous Self-Experience (EASE). These empirical studies support the classic clinical intuition that anomalous self-experiences form a central phenotype of schizophrenia. Implications for diagnosis and research are briefly discussed. PMID- 25126761 TI - Validity of heart failure diagnoses in administrative databases: a systematic review and meta-analysis. AB - OBJECTIVE: Heart failure (HF) is an important covariate and outcome in studies of elderly populations and cardiovascular disease cohorts, among others. Administrative data is increasingly being used for long-term clinical research in these populations. We aimed to conduct the first systematic review and meta analysis of studies reporting on the validity of diagnostic codes for identifying HF in administrative data. METHODS: MEDLINE and EMBASE were searched (inception to November 2010) for studies: (a) Using administrative data to identify HF; or (b) Evaluating the validity of HF codes in administrative data; and (c) Reporting validation statistics (sensitivity, specificity, positive predictive value [PPV], negative predictive value, or Kappa scores) for HF, or data sufficient for their calculation. Additional articles were located by hand search (up to February 2011) of original papers. Data were extracted by two independent reviewers; article quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Using a random-effects model, pooled sensitivity and specificity values were produced, along with estimates of the positive (LR+) and negative (LR ) likelihood ratios, and diagnostic odds ratios (DOR = LR+/LR-) of HF codes. RESULTS: Nineteen studies published from 1999-2009 were included in the qualitative review. Specificity was >=95% in all studies and PPV was >=87% in the majority, but sensitivity was lower (>=69% in >=50% of studies). In a meta analysis of the 11 studies reporting sensitivity and specificity values, the pooled sensitivity was 75.3% (95% CI: 74.7-75.9) and specificity was 96.8% (95% CI: 96.8-96.9). The pooled LR+ was 51.9 (20.5-131.6), the LR- was 0.27 (0.20 0.37), and the DOR was 186.5 (96.8-359.2). CONCLUSIONS: While most HF diagnoses in administrative databases do correspond to true HF cases, about one-quarter of HF cases are not captured. The use of broader search parameters, along with laboratory and prescription medication data, may help identify more cases. PMID- 25126766 TI - Fluorescence fluctuation microscopy: a diversified arsenal of methods to investigate molecular dynamics inside cells. AB - Fluorescence microscopy provides insight into the subcellular organization of biological functions. However, images are snap shots averaging over a highly dynamic molecular system. Fluorescence fluctuation microscopy, employing similar detection technology, encompasses a powerful arsenal of analysis tools that investigate the molecular heterogeneity in space and time. Analyzing signal fluctuations from small ensembles (several hundred particles) reveals their concentration, the stoichiometry, the stochastic motion, as well as superimposed signatures of the environment such as spatial confinement and binding events. Thus, fluctuation analysis provides access to dynamic molecular properties that can be used to build physical models of cellular processes. In the last decade these methods experienced a remarkable diversification, which we revisit here with a particular focus on live cell applications. PMID- 25126765 TI - High-speed AFM imaging. AB - Proteins are dynamic in nature and function at the single molecule level. To achieve a straightforward and in-depth understanding of their underlying functional mechanism, we need to directly observe protein molecules at work at high resolution, without the use of protein-attached markers. To realize such objectives, high-speed atomic force microscopy (HS-AFM) has been developed and recently its capability has been fully established. This approach opens a new avenue to directly and closely observe individual molecules at submolecular spatial resolution and sub-100 ms time resolution. The captured molecular movies of proteins directly report and provide great insights into how the proteins function. Moreover, the very recent progress of HS-AFM technology has extended its use to the observation of dynamic cellular processes. In this article, I review imaging studies to show the innovative power and potential of this new microscopy. PMID- 25126764 TI - Low molecular weight hyaluronan mediated CD44 dependent induction of IL-6 and chemokines in human dermal fibroblasts potentiates innate immune response. AB - Complex regulation of the wound healing process involves multiple interactions among stromal tissue cells, inflammatory cells, and the extracellular matrix. Low molecular weight hyaluronan (LMW HA) derived from the degradation of high molecular weight hyaluronan (HMW HA) is suggested to activate cells involved in wound healing through interaction with HA receptors. In particular, receptor CD44 is suggested to mediate cell response to HA of different MW, being the main cell surface HA receptor in stromal tissue and immune cells. However, the response of dermal fibroblasts, the key players in granulation tissue formation within the wound healing process, to LMW HA and their importance for the activation of immune cells is unclear. In this study we show that LMW HA (4.3kDa) induced pro inflammatory cytokine IL-6 and chemokines IL-8, CXCL1, CXCL2, CXCL6 and CCL8 gene expression in normal human dermal fibroblasts (NHDF) that was further confirmed by increased levels of IL-6 and IL-8 in cell culture supernatants. Conversely, NHDF treated by HMW HA revealed a tendency to decrease the gene expression of these cytokine and chemokines when compared to untreated control. The blockage of CD44 expression by siRNA resulted in the attenuation of IL-6 and chemokines expression in LMW HA treated NHDF suggesting the involvement of CD44 in LMW HA mediated NHDF activation. The importance of pro-inflammatory mediators produced by LMW HA triggered NHDF was evaluated by significant activation of blood leukocytes exhibited as increased production of IL-6 and TNF-alpha. Conclusively, we demonstrated a pro-inflammatory response of dermal fibroblasts to LMW HA that was transferred to leukocytes indicating the significance of LMW HA in the inflammatory process development during the wound healing process. PMID- 25126768 TI - Novel Pigtail Cannula for a Canalicular-Involving Eyelid Laceration. AB - An 89-year-old woman presented with a canalicular-involving laceration/avulsion of the right lower eyelid after a fall. The inferior canaliculus was severed deep within the wound, and the ends were difficult to identify. Novel pigtail cannulas, designed by the authors, were used for lacrimal system intubation and suture passage. Satisfactory cosmetic and functional results were achieved. These cannulas facilitate repair by integrating multiple functionalities in a single instrument. Once a cannula has been inserted and rotated, the location of fluid egress provides important clues. If injected saline appears in the nasopharynx but not in the wound, absence of a common canaliculus can be suspected. Injection of viscoelastic, air or fluorescein-impregnated saline also permits easier identification of the cut end of the canaliculus within the wound and facilitates appropriate rotation of the pigtail. PMID- 25126767 TI - Neurostimulation of the lacrimal nerve for enhanced tear production. AB - PURPOSE: To design a proof-of-concept study to assess the effect of lacrimal nerve stimulation (LNS) with an implantable pulse generator (IPG) to increase aqueous tear production. METHODS: Experimental animal study design of 6 Dutch Belted rabbits. Ultra high-resolution optical coherence tomography (UHR-OCT) quantified tear production by measuring the baseline tear volume of each rabbit's OD and OS. A neurostimulator was implanted adjacent to the right lacrimal nerve. After 2 minutes of LNS (100 MUs, 1.6 mA, 20 Hz, 5-8 V), the tear volumes were measured with UHR-OCT. The change in tear volume was quantified and compared with the nonstimulated OS. Three rabbits underwent chronic LNS (100 MUs, 1.6 mA, 10 Hz, 2 V) and their lacrimal glands were harvested for histopathologic analysis. RESULTS: The UHR-OCT imaging of the OD tear volume showed a 441% average increase in tear production after LNS as a percent of baseline. After stimulation, OD had statistically significant greater increase in tear volumes than OS (p = 0.028, Wilcoxon test). Poststimulation OD tear volumes were significantly greater compared with baseline (p = 0.028, Wilcoxon test). Histopathologic examination of the lacrimal glands showed no discernible tissue damage from chronic neurostimulation. In addition, there were no gross adverse effects on the general well-being of the animals due to chronic stimulation. CONCLUSIONS: LNS with an IPG appears to increase aqueous tear production. Chronic LNS showed no histopathologic lacrimal gland damage. This study suggests that LNS is a promising new treatment strategy to increase aqueous tear production. PMID- 25126769 TI - Risk of ocular blood splatter during oculofacial plastic surgery. AB - PURPOSE: To assess intraoperative blood splatter to the ocular surface and adnexa during oculofacial surgery. METHODS: Four surgeons and multiple assistants at three separate locations wore a total of 331 protective eye shields during 131 surgeries. Postoperatively, a luminol blood detection system was used to identify blood splatter on the shields. In the event of positive blood splatter, the total number of blood spots was counted. Controls were used to verify the blood detection protocol. A postoperative questionnaire was given to all surgeons and assistants after each case, and they were asked whether intraoperative blood splatter was noticed. RESULTS: Blood was detected on 61% of eye shields and in a total of 80% of surgical cases. However, only 2% of blood splatters were recognized intraoperatively by the surgical participants. There was no significant difference in the splatter rate between surgeons (64%), assistants (60%), and surgical technicians (58%) (p = 0.69). Shields worn during full thickness eyelid procedures, direct brow lifting, orbitotomy with bony window, and orbital fracture repairs were more likely to be splattered (p = 0.03), and there was a significant difference between splatter rates among different surgeons (range, 29-90%; p = 0.0004), suggesting that blood splatter rate may be both procedure dependent and surgeon dependent. CONCLUSIONS: Mucocutaneous and transconjunctival transmission of human immunodeficiency virus and viral hepatitis has been documented. These results suggest that oculofacial plastic surgeons should consider eye protection for patients with known blood-borne diseases and in cases where blood splatter is expected. This precautionary practice is supported by the high incidence (98%) of undetected, intraoperative blood splatter. PMID- 25126770 TI - Malignant melanoma of the lacrimal drainage apparatus complicating conjunctival melanoma. AB - PURPOSE: Melanoma of the conjunctiva may occasionally involve the lacrimal drainage apparatus (LDA). This makes clinical management difficult. The authors describe 5 cases of conjunctival melanoma with LDA disease and make recommendations about its management. METHODS: Retrospective review of case notes and histopathology reports. RESULTS: Five cases of LDA melanoma arising in patients with conjunctival melanoma are described. All 5 had orbital exenteration as part of their treatment. Melanoma of the LDA was clinically present at the time of exenteration in 1 case, found unexpectedly in 2 cases, and developed subsequent to exenteration in 2 cases. One patient died within 8 months of exenteration from metastatic melanoma. Two patients were disease free 3 and 5 years after exenteration. One patient developed metastasis in the parotid gland 4 years after exenteration but remained disease free 7 years after exenteration. One more patient has had a local recurrence in the maxilla and lateral nasal wall 4 years after exenteration, and after resection of that lesion and radiotherapy is disease free after 18 months. Seventeen patients underwent orbital exenteration for conjunctival melanoma over the period 1996-2013 at the authors'institution, with 5 having or developing LDA disease (29%). In the same period, there were 52 patients with conjunctival melanoma overall, with LDA involvement occurring in 5 of 52 patients (9.6%). CONCLUSIONS: Melanoma of the LDA may complicate conjunctival melanoma in a significant percentage of cases having orbital exenteration. The surgical technique for orbital exenteration in patients with conjunctival melanoma should take this into account by intentionally removing the lacrimal sac and upper nasolacrimal duct as well as the lacrimal canaliculi. If melanoma is found in the LDA, consideration should be given to wider en bloc excision of the LDA. PMID- 25126771 TI - Idiopathic Orbital Inflammation Associated With Necrotizing Scleritis and Temporal Bone Inflammation. AB - The authors present a case of aggressive idiopathic orbital inflammation producing necrotizing scleritis along with synchronous tumefactive fibroinflammatory lesion of the temporal bone. A young woman with no medical history presented with sectoral scleritis and mildly reduced vision. Response to initial treatment, which included topical and systemic corticosteroids, as well as systemic nonsteroidal anti-inflammatory drugs, was limited. Over the following months, signs of orbital inflammation developed, including ptosis, proptosis, and limited extraocular motility. MRI revealed both orbital and ipsilateral temporal bone masses. An orbital biopsy was performed revealing a mixed inflammatory infiltrate, whereas a biopsy of the temporal bone mass revealed a tumefactive fibroinflammatory lesion. Biopsy showed no histopathologic evidence of infection nor neoplasm. The patient eventually responded to treatment with systemic prednisone, azathioprine, and rituximab. PMID- 25126772 TI - Dacryocystitis As the Initial Presentation of Invasive Fungal Sinusitis in Immunocompromised Children. AB - Sino-orbital fungal infection is a rare, but life-threatening disease seen mainly in immunocompromised patients. While initial clinical impression may vary, dacryocystitis has rarely been described as the initial presenting sign. The authors present 2 pediatric cases of dacryocystitis as the initial sign of invasive fungal sinusitis. To their knowledge, this presenting sign has not been previously reported in the pediatric population. Management strategies and outcomes are discussed. PMID- 25126773 TI - Magnesium sulphate for preventing preterm birth in threatened preterm labour. AB - BACKGROUND: Magnesium sulphate has been used in some settings as a tocolytic agent to inhibit uterine activity in women in preterm labour with the aim of preventing preterm birth. OBJECTIVES: To assess the effects of magnesium sulphate therapy given to women in threatened preterm labour with the aim of preventing preterm birth and its sequelae. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (last searched 31 January 2014). SELECTION CRITERIA: Randomised controlled trials of magnesium sulphate as the only tocolytic, administered by any route, compared with either placebo, no treatment or alternative tocolytic therapy (not magnesium sulphate) to women considered to be in preterm labour. DATA COLLECTION AND ANALYSIS: At least two review authors assessed trial eligibility and risk of bias and undertook data extraction independently. MAIN RESULTS: The 37 included trials (total of 3571 women and over 3600 babies) were generally of moderate to high risk of bias. Antenatal magnesium sulphate was compared with either placebo, no treatment, or a range of alternative tocolytic agents.For the primary outcome of giving birth within 48 hours after trial entry, no significant differences were seen between women who received magnesium sulphate and women who did not (whether placebo/no alternative tocolytic drug, betamimetics, calcium channel blockers, cox inhibitors, prostaglandin inhibitors, or human chorionic gonadotropin) (19 trials, 1913 women). Similarly for the primary outcome of serious infant outcome, there were no significant differences between the infants exposed to magnesium sulphate and those not (whether placebo/no alternative tocolytic drug, betamimetics, calcium channel blockers, cox inhibitors, prostaglandin inhibitors, human chorionic gonadotropin or various tocolytic drugs) (18 trials; 2187 babies). No trials reported the outcome of extremely preterm birth. In the seven trials that reported serious maternal outcomes, no events were recorded.In the group treated with magnesium sulphate compared with women receiving antenatal placebo or no alternative tocolytic drug, a borderline increased risk of total death (fetal, neonatal, infant) was seen (risk ratio (RR) 4.56, 95% confidence interval (CI) 1.00 to 20.86; two trials, 257 babies); none of the comparisons between magnesium sulphate and other classes of tocolytic drugs showed differences for this outcome (10 trials, 991 babies). The outcomes of neonatal and/or infant deaths and of fetal deaths did not show differences between magnesium sulphate and no magnesium sulphate, whether compared with placebo/no alternative tocolytic drug, or any specific class of tocolytic drug. For most of the other secondary outcomes, there were no significant differences between magnesium sulphate and the control groups for risk of preterm birth (except for a significantly lower risk with magnesium sulphate when compared with barbiturates in one trial of 65 women), gestational age at birth, interval between trial entry and birth, other neonatal morbidities, or neurodevelopmental outcomes. Duration of neonatal intensive care unit stay was significantly increased in the magnesium sulphate group compared with the calcium channel blocker group, but not when compared with cox inhibitors or prostaglandin inhibitors. No maternal deaths were reported in the four trials reporting this outcome. Significant differences between magnesium sulphate and controls were not seen for maternal adverse events severe enough to stop treatment, except for a significant benefit of magnesium sulphate compared with betamimetics in a single trial. AUTHORS' CONCLUSIONS: Magnesium sulphate is ineffective at delaying birth or preventing preterm birth, has no apparent advantages for a range of neonatal and maternal outcomes as a tocolytic agent and its use for this indication may be associated with an increased risk of total fetal, neonatal or infant mortality (in contrast to its use in appropriate groups of women for maternal, fetal, neonatal and infant neuroprotection where beneficial effects have been demonstrated). PMID- 25126774 TI - [Two forms of familial hypercholesterolemia: differences in cardiovascular risk factors, cardiac and extracardiac atherosclerosis]. AB - BACKGROUND AND AIM: The monogenetic hypercholesterolemias (HC) are associated with a very high risk of premature coronary heart disease (CHD). We sought to assess the influence of the genetic defect and the cardiovascular risk factors on the manifestation of atherosclerotic complications in two forms of genetic HC. PATIENTS AND METHODS: Data of patients with genetically defined HC (54 LDL receptor defective familial hypercholesterolemia (FH) and 54 familial defective apolipoprotein B (FDB)) were analysed retrospectively for cardiac and extracardiac atherosclerosis. RESULTS: Total and LDL-cholesterol were significantly higher in FH men than in FDB men, but not so in women. 41.8% of FH patients had CHD (mean age 41 years), 5.6% of FDB (mean age 52 years). Stenoses (>50% narrowing) of the internal carotid artery were verified in 15% of FH and 4% of FDB patients. Peripheral arterial disease was found in 3 FH and 2 FDB patients. Hypertension and active smoking were allotted almost equally, body weight was normal in most of the patients (BMI <= 25 kg/m(2)). Conlusion: Patients with genetic HC suffer from early manifestation of cardiac disease. Patients with FH seem to be affected more often than patients with FDB. Early diagnosis and early and lifelong treatment are essential and, according to the literature, lead to a delay of disease manifestation. PMID- 25126775 TI - Fish population studies using parasites from the Southeastern Pacific Ocean: considering host population changes and species body size as sources of variability of parasite communities. AB - Research using parasites in fish population studies in the South Eastern Pacific (SEP) is summarized. There are 27 such studies (snapshots mainly) in single host species sampled at different geographic localities and at somewhat similar times. They have been devoted mainly to economically important species, though others on coastal and intertidal fish or on less- or non-commercial species provide insights on scales of temporal and spatial variation of parasite infracommunities. Later, we assess whether the probability of harbouring parasites depends on the host species body size. Our results indicate that a stronger tool for fish population studies may be developed under regular (long term) scrutiny of parasite communities, especially of small fish host species, due to their larger variability in richness, abundance and total biomass, than in large fish species. Finally, it might also be necessary to consider the effects of fishing on parasite communities as well as the natural oscillations (coupled or not) of host and parasite populations. PMID- 25126776 TI - Hippo pathway key to ploidy checkpoint. AB - Tetraploid cells generated by abnormal cell division are often arrested during the cell cycle or cleared by apoptosis. Evasion of these defense mechanisms leads to genomic instability and tumorigenesis. In this issue, Ganem et al. report that extra centrosome-induced activation of the Hippo pathway kinase LATS2 is a key mechanism of tetraploidy-induced cell-cycle arrest. PMID- 25126777 TI - A timeless but timely connection between replication and recombination. AB - Initiation of meiotic recombination by DNA double-strand break formation is temporally coordinated with replication. Murakami and Keeney show that this coordination requires recruitment of the Dbf4-dependent kinase to the replication fork by the conserved TIM-TIPIN complex. The same mechanism may regulate other important replication-associated processes. PMID- 25126778 TI - CellNet--where your cells are standing. AB - The manufacturing of clinically relevant cells is a widely used strategy in regenerative medicine. Cahan et al. develop a network biology platform named CellNet to accurately assess the fidelity of such cells and spot aberrant regulatory networks, and Morris et al. apply this platform to improve cell manufacturing. PMID- 25126779 TI - Lights, X-rays, oxygen! AB - Photosystem II uses metal ions to oxidize water to form O2. Two recent papers employ the new technique of serial femtosecond crystallography utilizing X-ray free-electron lasers and nanocrystals to obtain initial structures of intermediate states of photosystem II catalysis at the site of oxygen production. PMID- 25126781 TI - Phenotypic variation of Salmonella in host tissues delays eradication by antimicrobial chemotherapy. AB - Antibiotic therapy often fails to eliminate a fraction of transiently refractory bacteria, causing relapses and chronic infections. Multiple mechanisms can induce such persisters with high antimicrobial tolerance in vitro, but their in vivo relevance remains unclear. Using a fluorescent growth rate reporter, we detected extensive phenotypic variation of Salmonella in host tissues. This included slow growing subsets as well as well-nourished fast-growing subsets driving disease progression. Monitoring of Salmonella growth and survival during chemotherapy revealed that antibiotic killing correlated with single-cell division rates. Nondividing Salmonella survived best but were rare, limiting their impact. Instead, most survivors originated from abundant moderately growing, partially tolerant Salmonella. These data demonstrate that host tissues diversify pathogen physiology, with major consequences for disease progression and control. PMID- 25126780 TI - Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. AB - Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high fat diet induced obesity. The growth promotion phenotype is transferrable to germ free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. PAPERCLIP: PMID- 25126782 TI - Function of a Foxp3 cis-element in protecting regulatory T cell identity. AB - The homeostasis of multicellular organisms requires terminally differentiated cells to preserve their lineage specificity. However, it is unclear whether mechanisms exist to actively protect cell identity in response to environmental cues that confer functional plasticity. Regulatory T (Treg) cells, specified by the transcription factor Foxp3, are indispensable for immune system homeostasis. Here, we report that conserved noncoding sequence 2 (CNS2), a CpG-rich Foxp3 intronic cis-element specifically demethylated in mature Tregs, helps maintain immune homeostasis and limit autoimmune disease development by protecting Treg identity in response to signals that shape mature Treg functions and drive their initial differentiation. In activated Tregs, CNS2 helps protect Foxp3 expression from destabilizing cytokine conditions by sensing TCR/NFAT activation, which facilitates the interaction between CNS2 and Foxp3 promoter. Thus, epigenetically marked cis-elements can protect cell identity by sensing key environmental cues central to both cell identity formation and functional plasticity without interfering with initial cell differentiation. PMID- 25126783 TI - Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus. AB - In multicellular organisms, specialized functions are delegated to distinct cell types whose identity and functional integrity are maintained upon challenge. However, little is known about the mechanisms enabling lineage inheritance and their biological implications. Regulatory T (Treg) cells, which express the transcription factor Foxp3, suppress fatal autoimmunity throughout the lifespan of animals. Here, we show that a dedicated Foxp3 intronic element CNS2 maintains Treg cell lineage identity by acting as a sensor of the essential Treg cell growth factor IL-2 and its downstream target STAT5. CNS2 sustains Foxp3 expression during division of mature Treg cells when IL-2 is limiting and counteracts proinflammatory cytokine signaling that leads to the loss of Foxp3. CNS2-mediated stable inheritance of Foxp3 expression is critical for adequate suppression of diverse types of chronic inflammation by Treg cells and prevents their differentiation into inflammatory effector cells. The described mechanism may represent a general principle of the inheritance of differentiated cell states. PMID- 25126785 TI - Type II cadherins guide assembly of a direction-selective retinal circuit. AB - Complex retinal circuits process visual information and deliver it to the brain. Few molecular determinants of synaptic specificity in this system are known. Using genetic and optogenetic methods, we identified two types of bipolar interneurons that convey visual input from photoreceptors to a circuit that computes the direction in which objects are moving. We then sought recognition molecules that promote selective connections of these cells with previously characterized components of the circuit. We found that the type II cadherins, cdh8 and cdh9, are each expressed selectively by one of the two bipolar cell types. Using loss- and gain-of-function methods, we showed that they are critical determinants of connectivity in this circuit and that perturbation of their expression leads to distinct defects in visually evoked responses. Our results reveal cellular components of a retinal circuit and demonstrate roles of type II cadherins in synaptic choice and circuit function. PMID- 25126784 TI - Stem-loop recognition by DDX17 facilitates miRNA processing and antiviral defense. AB - DEAD-box helicases play essential roles in RNA metabolism across species, but emerging data suggest that they have additional functions in immunity. Through RNAi screening, we identify an evolutionarily conserved and interferon independent role for the DEAD-box helicase DDX17 in restricting Rift Valley fever virus (RVFV), a mosquito-transmitted virus in the bunyavirus family that causes severe morbidity and mortality in humans and livestock. Loss of Drosophila DDX17 (Rm62) in cells and flies enhanced RVFV infection. Similarly, depletion of DDX17 but not the related helicase DDX5 increased RVFV replication in human cells. Using crosslinking immunoprecipitation high-throughput sequencing (CLIP-seq), we show that DDX17 binds the stem loops of host pri-miRNA to facilitate their processing and also an essential stem loop in bunyaviral RNA to restrict infection. Thus, DDX17 has dual roles in the recognition of stem loops: in the nucleus for endogenous microRNA (miRNA) biogenesis and in the cytoplasm for surveillance against structured non-self-elements. PMID- 25126786 TI - State-dependent architecture of thalamic reticular subnetworks. AB - Behavioral state is known to influence interactions between thalamus and cortex, which are important for sensation, action, and cognition. The thalamic reticular nucleus (TRN) is hypothesized to regulate thalamo-cortical interactions, but the underlying functional architecture of this process and its state dependence are unknown. By combining the first TRN ensemble recording with psychophysics and connectivity-based optogenetic tagging, we found reticular circuits to be composed of distinct subnetworks. While activity of limbic-projecting TRN neurons positively correlates with arousal, sensory-projecting neurons participate in spindles and show elevated synchrony by slow waves during sleep. Sensory projecting neurons are suppressed by attentional states, demonstrating that their gating of thalamo-cortical interactions is matched to behavioral state. Bidirectional manipulation of attentional performance was achieved through subnetwork-specific optogenetic stimulation. Together, our findings provide evidence for differential inhibition of thalamic nuclei across brain states, where the TRN separately controls external sensory and internal limbic processing facilitating normal cognitive function. PAPERFLICK: PMID- 25126787 TI - Probing the stochastic, motor-driven properties of the cytoplasm using force spectrum microscopy. AB - Molecular motors in cells typically produce highly directed motion; however, the aggregate, incoherent effect of all active processes also creates randomly fluctuating forces, which drive diffusive-like, nonthermal motion. Here, we introduce force-spectrum-microscopy (FSM) to directly quantify random forces within the cytoplasm of cells and thereby probe stochastic motor activity. This technique combines measurements of the random motion of probe particles with independent micromechanical measurements of the cytoplasm to quantify the spectrum of force fluctuations. Using FSM, we show that force fluctuations substantially enhance intracellular movement of small and large components. The fluctuations are three times larger in malignant cells than in their benign counterparts. We further demonstrate that vimentin acts globally to anchor organelles against randomly fluctuating forces in the cytoplasm, with no effect on their magnitude. Thus, FSM has broad applications for understanding the cytoplasm and its intracellular processes in relation to cell physiology in healthy and diseased states. PMID- 25126788 TI - Cytokinesis failure triggers hippo tumor suppressor pathway activation. AB - Genetically unstable tetraploid cells can promote tumorigenesis. Recent estimates suggest that ~37% of human tumors have undergone a genome-doubling event during their development. This potentially oncogenic effect of tetraploidy is countered by a p53-dependent barrier to proliferation. However, the cellular defects and corresponding signaling pathways that trigger growth suppression in tetraploid cells are not known. Here, we combine RNAi screening and in vitro evolution approaches to demonstrate that cytokinesis failure activates the Hippo tumor suppressor pathway in cultured cells, as well as in naturally occurring tetraploid cells in vivo. Induction of the Hippo pathway is triggered in part by extra centrosomes, which alter small G protein signaling and activate LATS2 kinase. LATS2 in turn stabilizes p53 and inhibits the transcriptional regulators YAP and TAZ. These findings define an important tumor suppression mechanism and uncover adaptive mechanisms potentially available to nascent tumor cells that bypass this inhibitory regulation. PMID- 25126789 TI - Reactivation of developmentally silenced globin genes by forced chromatin looping. AB - Distal enhancers commonly contact target promoters via chromatin looping. In erythroid cells, the locus control region (LCR) contacts beta-type globin genes in a developmental stage-specific manner to stimulate transcription. Previously, we induced LCR-promoter looping by tethering the self-association domain (SA) of Ldb1 to the beta-globin promoter via artificial zinc fingers. Here, we show that targeting the SA to a developmentally silenced embryonic globin gene in adult murine erythroblasts triggers its transcriptional reactivation. This activity depends on the LCR, consistent with an LCR-promoter looping mechanism. Strikingly, targeting the SA to the fetal gamma-globin promoter in primary adult human erythroblasts increases gamma-globin promoter-LCR contacts, stimulating transcription to approximately 85% of total beta-globin synthesis, with a reciprocal reduction in adult beta-globin expression. Our findings demonstrate that forced chromatin looping can override a stringent developmental gene expression program and suggest a novel approach to control the balance of globin gene transcription for therapeutic applications. PMID- 25126790 TI - Temporospatial coordination of meiotic DNA replication and recombination via DDK recruitment to replisomes. AB - It has been long appreciated that, during meiosis, DNA replication is coordinated with the subsequent formation of the double-strand breaks (DSBs) that initiate recombination, but a mechanistic understanding of this process was elusive. We now show that, in yeast, the replisome-associated components Tof1 and Csm3 physically associate with the Dbf4-dependent Cdc7 kinase (DDK) and recruit it to the replisome, where it phosphorylates the DSB-promoting factor Mer2 in the wake of the replication fork, synchronizing replication with an early prerequisite for DSB formation. Recruiting regulatory kinases to replisomes may be a general mechanism to ensure spatial and temporal coordination of replication with other chromosomal processes. PMID- 25126791 TI - Ecdysone and mediator change energy metabolism to terminate proliferation in Drosophila neural stem cells. AB - Stem cells are highly abundant during early development but become a rare population in most adult organs. The molecular mechanisms causing stem cells to exit proliferation at a specific time are not well understood. Here, we show that changes in energy metabolism induced by the steroid hormone ecdysone and the Mediator initiate an irreversible cascade of events leading to cell-cycle exit in Drosophila neural stem cells. We show that the timely induction of oxidative phosphorylation and the mitochondrial respiratory chain are required in neuroblasts to uncouple the cell cycle from cell growth. This results in a progressive reduction in neuroblast cell size and ultimately in terminal differentiation. Brain tumor mutant neuroblasts fail to undergo this shrinkage process and continue to proliferate until adulthood. Our findings show that cell size control can be modified by systemic hormonal signaling and reveal a unique connection between metabolism and proliferation in stem cells. PMID- 25126792 TI - Dissecting engineered cell types and enhancing cell fate conversion via CellNet. AB - Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells. PMID- 25126793 TI - CellNet: network biology applied to stem cell engineering. AB - Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. PMID- 25126796 TI - Severe sepsis outcomes: how are we doing?*. PMID- 25126797 TI - Who decides who should benefit? Allocating critical care in the context of "futile treatment"*. PMID- 25126798 TI - Why knowing the effects of positive-pressure ventilation on venous, pleural, and pericardial pressures is important to the bedside clinician?*. PMID- 25126794 TI - Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate. AB - A central problem in biology is to identify gene function. One approach is to infer function in large supergenomic networks of interactions and ancestral relationships among genes; however, their analysis can be computationally prohibitive. We show here that these biological networks are compressible. They can be shrunk dramatically by eliminating redundant evolutionary relationships, and this process is efficient because in these networks the number of compressible elements rises linearly rather than exponentially as in other complex networks. Compression enables global network analysis to computationally harness hundreds of interconnected genomes and to produce functional predictions. As a demonstration, we show that the essential, but functionally uncharacterized Plasmodium falciparum antigen EXP1 is a membrane glutathione S-transferase. EXP1 efficiently degrades cytotoxic hematin, is potently inhibited by artesunate, and is associated with artesunate metabolism and susceptibility in drug-pressured malaria parasites. These data implicate EXP1 in the mode of action of a frontline antimalarial drug. PMID- 25126799 TI - The valuable contribution of spiritual care to end-of-life care in the ICU*. PMID- 25126800 TI - It's not "do" but "why do" rapid response systems work?*. PMID- 25126801 TI - From storm to suppression in sepsis: are bands the link?*. PMID- 25126802 TI - Biomarkers to detect sepsis: a "burning" issue but still a long way to go*. PMID- 25126803 TI - Why do-not-resuscitate orders matter in comparative effectiveness research*. PMID- 25126804 TI - Anemia in the critically ill: do we need to live with it?*. PMID- 25126805 TI - Acute kidney injury after cardiac surgery: the injury that keeps on hurting?*. PMID- 25126806 TI - "The rhythm is gonna get you...": extracorporeal membrane oxygenation with and without intra-aortic balloon pumps*. PMID- 25126807 TI - Does the reperfusing brain recover better under pressure?*. PMID- 25126808 TI - Death in the ICU: when comfort is therapeutic*. PMID- 25126809 TI - Clearing lactate is clearly better...but how much?*. PMID- 25126810 TI - The impact of possible clonal spread of Acinetobacter baumannii complex bacteremia. PMID- 25126811 TI - The authors reply. PMID- 25126812 TI - What is the impact of catheter removal on the outcome of non-catheter-related candidemia? PMID- 25126813 TI - The authors reply. PMID- 25126814 TI - Conservative oxygen therapy in mechanically ventilated patients. PMID- 25126815 TI - The authors reply. PMID- 25126816 TI - Is the revised cardiac risk index the right risk index for vascular surgery patients? PMID- 25126817 TI - The authors reply. PMID- 25126818 TI - Mitochondrial respiration and passive stretch of the diaphragm during unilateral phrenic nerve stimulation. PMID- 25126819 TI - The authors reply. PMID- 25126820 TI - From targeting to optimizing cerebral perfusion pressure. PMID- 25126821 TI - The authors reply. PMID- 25126822 TI - Time to declare a moratorium on stress ulcer prophylaxis in critically ill. PMID- 25126823 TI - The authors reply. PMID- 25126824 TI - Mutation strategies for obtaining chitooligosaccharides with longer chains by transglycosylation reaction of family GH18 chitinase. AB - Enhancing the transglycosylation (TG) activity of glycoside hydrolases does not always result in the production of oligosaccharides with longer chains, because the TG products are often decomposed into shorter oligosaccharides. Here, we investigated the mutation strategies for obtaining chitooligosaccharides with longer chains by means of TG reaction catalyzed by family GH18 chitinase A from Vibrio harveyi (VhChiA). HPLC analysis of the TG products from incubation of chitooligosaccharide substrates, GlcNAc(n), with several mutant VhChiAs suggested that mutant W570G (mutation of Trp570 to Gly) and mutant D392N (mutation of Asp392 to Asn) significantly enhanced TG activity, but the TG products were immediately hydrolyzed into shorter GlcNAc(n). On the other hand, the TG products obtained from mutants D313A and D313N (mutations of Asp313 to Ala and Asn, respectively) were not further hydrolyzed, leading to the accumulation of oligosaccharides with longer chains. The data obtained from the mutant VhChiAs suggested that mutations of Asp313, the middle aspartic acid residue of the DxDxE catalytic motif, to Ala and Asn are most effective for obtaining chitooligosaccharides with longer chains. PMID- 25126825 TI - Explaining women's high satisfaction with objectively poor quality childbirth services: Armenia as a case study. AB - Despite documented low-quality care in Armenia, surveys document high ratings of patient satisfaction with health care services. We explored reasons for high satisfaction in Armenia despite poor quality. Twenty-five women who recently delivered participated in this qualitative study through in-depth interviews. Patients avoided critiquing health care services because of personal relationships with and respect for providers and fear of losing services. Although they shared an understanding of what quality care should be, many were satisfied because their low expectations were met. Further mixed methods research may explain this dissonance. Until then, patient satisfaction measures need careful, contextual interpretations. PMID- 25126826 TI - Changes in markers of brain serotonin activity in response to chronic exercise in senior men. AB - Aging is associated with noticeable impairments in brain serotonin transmission, which might contribute to increased vulnerability to developing depression in later life. Animal and human studies have shown that aerobic exercise can stimulate brain serotonin activity and trigger parallel elevations in tryptophan (TRP, the serotonin precursor) availability in blood plasma. However, the influence of chronic exercise on serotonergic activity in older adults is not yet known. Sixteen men aged 64 +/- 3 years exercised for 1 h (67%-70% peak oxygen consumption) at baseline and following 16 weeks of aerobic training. The main outcome measures were cardiorespiratory fitness, body composition, branched-chain amino acids (BCAA), TRP, prolactin, lactate, and free fatty acids (FFA). Changes in plasma free-TRP/BCAA and prolactin served as surrogates for TRP availability and serotonin activity, respectively. Chronic exercise decreased body mass (P < 0.05) whilst it increased ventilatory threshold 2 (P < 0.01). Although training did not affect plasma TRP availability to the brain at rest, both pre- and post training exercise challenges markedly increased TRP availability (P < 0.001). The free-TRP/BCAA values reached a ceiling during exercise that was lower following training (P < 0.05), whereas similar patterns were found for prolactin, lactate, and FFA. These data show that aerobic exercise elicits consistent transient elevations in plasma TRP availability to the brain in older men; the elevations were independent from physical training, although less pronounced following training. The data support the contention that repeated elevations in brain serotonin activity might be involved in the antidepressant effect of exercise training in older adults. PMID- 25126827 TI - Functional interleukin-21 polymorphism is a protective factor of diffuse large B cell lymphoma. AB - Interleukin-21 (IL-21) is a recently discovered cytokine and plays critical roles in antitumor immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. In this study, we investigated the association between IL-21 genetic polymorphisms and the susceptibility to DLBCL, and the possible functions of these polymorphisms. Two IL-21 polymorphisms, rs907715G/A and rs2221903A/G, were examined in 212 DLBCL patients and 232 healthy controls. Data showed that percentages of rs907715GA and AA genotypes were significantly lower in patients than in controls (odds ratio [OR]=0.60, 95% confidence interval [CI]: 0.40-0.90, p=0.014; OR=0.31, 95% CI: 0.17-0.56, p<0.001, respectively). Frequency of the rs2221903A/G polymorphism did not reveal any significant differences between patients and healthy donors. Further analyses demonstrated a significantly decreased number of rs907715AA genotype in patients with advanced Ann Arbor stages (III+IV). Moreover, we investigated the correlation between IL-21 polymorphisms and serum level of IL-21. Results showed that subjects carrying rs907715AA had significantly increased level of IL-21 than those with GG genotype or GA genotype. These data suggest that rs907715G/A polymorphism may act as a protective factor of DLBCL and might affect the serum level of IL-21. PMID- 25126828 TI - Nocardia farcinica brain abscess: epidemiology, pathophysiology, and literature review. AB - BACKGROUND: Infections caused by Nocardia farcinica are potentially lethal because of the organism's tendency to disseminate and resist antibiotics. Central nervous system involvement has been documented in 30% of infections caused N. farcinica. METHODS: Case report and review of the literature. RESULTS: A case of primary brain abscess caused by N. farcinica, identified by 16SrRNA sequencing, is presented, and 39 cases reported previously in the literature are reviewed. Our patient underwent a neuronavigation-guided right frontal craniotomy and was treated with trimethoprim/sulfamethoxazole and amoxicillin-clavulanic acid for 12 mo. He showed marginal improvement in his prior left hemiparesis at the last review 14 months later. CONCLUSION: Cases of N. farcinica infections are being reported increasingly because of recent changes in taxonomy and diagnostic methodology. This change in epidemiology has implications for therapy because of the organism's pathogenicity and natural resistance to multiple antimicrobial agents, including third-generation cephalosporins. Any delay in starting appropriate antibiotic therapy can have adverse consequences. PMID- 25126829 TI - Transnationals' experience of dying in their adopted country: a systematic review. AB - BACKGROUND: Social and emotional challenges of migration and integration include managing memories and perceptions of country of birth, leaving loved relatives behind, and the challenges of maintaining traditions, such as cultural food and practices. For many migrants, the strong connection with their birth country is never completely severed, which may become pertinent at particular events and stages in life with inherent emotional impact. This may be particularly the case for end-of-life experience. OBJECTIVE: We undertook a systematic review of published evidence of research to identify the lived experience of migrants dying in a country different from their country of birth. DESIGN: The search terms [transnationals OR migran* OR immigran*] AND [emotions OR belonging OR acculturation OR national identity] AND [dying OR end-of-life OR contemplation of dying] AND [palliative care OR terminal care] were used on the following electronic databases: MEDLINE, Embase, CINAHL, EBSCO, Geobase, PsychINFO, and Scopus to the end date of January 2014. No date limit was imposed. All research methodologies were included. The search was restricted to human subjects and English language. RESULTS: Seven qualitative studies met the criteria. Thematic analysis of these studies identified three main themes: sense of dual identity, importance of traditions from their country of origin, and dying preferences. CONCLUSION: Findings have implications for the provision of palliative end-of life care for dying transnationals, particularly in relation to providing support for migrants who are dying to resolve social and emotional issues. PMID- 25126831 TI - Development and evaluation of ITS- and aflP-based LAMP assays for rapid detection of Aspergillus flavus in food samples. AB - Aspergillus flavus is a common filamentous fungus that produces aflatoxins and presents a major threat to agriculture and human health. Previous studies focused mainly on the detection of A. flavus or aflatoxin separately. Here, we developed internal transcribed spacer (ITS)- and aflP-based rapid detection of A. flavus in food samples using the loop-mediated isothermal amplification (LAMP) method. The ITS1-5.8S-ITS2 rDNA region of A. flavus and the aflatoxin-encoding gene aflP were used as target regions. The detection limits of A. flavus and aflP were 10 fg and 1 pg pure DNA, respectively, which allows aflatoxin-contaminated samples to be differentiated from infected samples and reduces false-negative or false-positive results. For specificity testing, DNA extracted from 7 A. flavus, 5 different Aspergillus spp., and 21 other fungi were used, and our results showed that A. flavus strains are detected by ITS-based detection and aflatoxigenic A. flavus strains are detected by aflP-based detection. Furthermore, the ITS- and aflP based LAMP assays were used for detection analysis of DNA from food samples artificially and naturally contaminated with A. flavus. Our results showed that the detection rate of A. flavus based on the multi-ITS-based LAMP detection is 100% and that the aflatoxigenic strains in all A. flavus are detected by the aflP based LAMP assay. The LAMP protocol described in our study represents a rapid and highly specific and sensitive diagnostic method for A. flavus detection, which can be used as a diagnostic tool that simplifies A. flavus monitoring and guarantees the quality and safety of foods. PMID- 25126832 TI - Plasmonic Ag@AgCl nanotubes fabricated from copper nanowires as high-performance visible light photocatalyst. AB - In this paper, plasmonic photocatalyst Ag@AgCl nanotubes were prepared by a cost efficient and template-based method and their photocatalytic properties were studied. In the synthesis, copper nanowires were first synthesized and Ag nanotubes were then obtained through the galvanic reaction between copper and Ag ions. The formation of Ag@AgCl nanotubes was finally achieved by in situ oxidation reaction upon the addition of FeCl3. The crystal structure of the product was characterized by X-ray powder diffraction. The morphology and composition of the composite were studied by scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy measurements. All the structure characterizations showed that the tubulate product was produced by the synthetic processes. By using the obtained product as photocatalyst, the photodegradation of methyl orange (MO) was investigated under visible light. The experimental results showed that the as-prepared Ag@AgCl nanotubes exhibit excellent photocatalytic performance and high stability. Under visible light irradiation, more than 92.58% of the MO dye has been decomposed in 10 min on the product with a 1:1 ratio of Fe/Ag. On the basis of the proposed mechanism, the improved photocatalytic activities of the Ag@AgCl hybrids can be ascribed to the enhanced surface area for dye molecule adsorption, enhanced visible light absorbance, and the efficient charge separation of the hybrid nanostructures. PMID- 25126830 TI - Executive function late effects in survivors of pediatric brain tumors and acute lymphoblastic leukemia. AB - BACKGROUND: Survivors of pediatric brain tumors (BT) and acute lymphoblastic leukemia (ALL) are at risk for neurocognitive late effects related to executive function. PROCEDURE: Survivors of BT (48) and ALL (50) completed neurocognitive assessment. Executive function was compared to estimated IQ and population norms by diagnostic group. RESULTS: Both BT and ALL demonstrated relative executive function weaknesses. As a group, BT survivors demonstrated weaker executive functioning than expected for age. Those BT survivors with deficits exhibited a profile suggestive of global executive dysfunction, while affected ALL survivors tended to demonstrate specific rapid naming deficits. CONCLUSION: Findings suggest that pediatric BT and ALL survivors may exhibit different profiles of executive function late effects, which may necessitate distinct intervention plans. PMID- 25126834 TI - Enhancing photoinduced electron transfer efficiency of fluorescent pH-probes with halogenated phenols. AB - Photoinduced electron transfer (PET), which causes pH-dependent quenching of fluorescent dyes, is more effectively introduced by phenolic groups than by amino groups which have been much more commonly used so far. That is demonstrated by fluorescence measurements involving several classes of fluorophores. Electrochemical measurements show that PET in several amino-modified dyes is thermodynamically favorable, even though it was not experimentally found, underlining the importance of kinetic aspects to the process. Consequently, the attachment of phenolic groups allows for fast and simple preparation of a wide selection of fluorescent pH-probes with tailor-made spectral properties, sensitive ranges, and individual advantages, so that a large number of applications can be realized. Fluorophores carrying phenolic groups may also be used for sensing analytes other than pH or molecular switching and signaling. PMID- 25126835 TI - Inhibition of protein and cell attachment on materials generated from N-(2 hydroxypropyl) acrylamide. AB - Effective control over biointerfacial interactions is essential for a broad range of biomedical applications. At this point in time, only a relatively small range of radically polymerizable monomers have been described that are able to generate low fouling polymer materials and surfaces. The most important examples that have been successfully used in the context of the reduction of nonspecific protein adsorption and subsequent cell attachment include PEG-based monomers such as poly(ethylene glycol) methacrylate (PEGMA), zwitterionic monomers such as 2 methacryloyloxyethyl phosphorylcholine and noncharged monomers such as acrylamide and N-(2-hydroxypropyl) methacrylamide (HPMAm). However, issues such as oxidative degradation and poor polymerization characteristics limit the applicability of most of these candidates. Here we have synthesized the monomer N-(2 hydroxypropyl) acrylamide (HPAm), examined its polymerization kinetics and evaluated its suitability for RAFT mediated polymerization in comparison to HPMAm. We also synthesized hydrogels using HPMAm and HPAm and evaluated the ability of HPAm polymers to occlude protein adsorption and cell attachment. In RAFT-controlled polymerization, much faster (8*) polymerization was observed for HPAm relative to HPMAm and better control was achieved over the molecular weight distribution. The performance of hydrogels prepared from HPAm in the prevention of protein adsorption and cellular attachment was equivalent to or better than that observed for materials made from HPMAm and PEG. These results open the door for HPAm based polymers in applications where effective control over biointerfacial interactions is required. PMID- 25126836 TI - Chiral phosphoric acid catalyzed highly enantioselective desymmetrization of 2 substituted and 2,2-disubstituted 1,3-diols via oxidative cleavage of benzylidene acetals. AB - A highly enantioselective catalytic protocol for the desymmetrization of a wide variety of 2-substituted and 2,2-disubstituted 1,3-diols is reported. This reaction proceeds through the formation of an "ortho ester" intermediate via oxidation of 1,3-diol benzylidene acetal by dimethyldioxirane (DMDO) and the subsequent proton transfer catalyzed by chiral phosphoric acid (CPA). The mechanism and origins of enantioselectivity of this reaction are identified using DFT calculations. The oxidation by DMDO is rate-determining, and the phosphoric acid significantly accelerates the proton transfer; the attractive interactions between the benzylidene part of the substrate and the 2,4,6-triisopropyl group of CPA are the key to high enantioselectivity. PMID- 25126833 TI - Design, synthesis, and structure-activity relationship studies of a series of [4 (4-carboxamidobutyl)]-1-arylpiperazines: insights into structural features contributing to dopamine D3 versus D2 receptor subtype selectivity. AB - Antagonist and partial agonist modulators of the dopamine D3 receptor (D3R) have emerged as promising therapeutics for the treatment of substance abuse and neuropsychiatric disorders. However, development of druglike lead compounds with selectivity for the D3 receptor has been challenging because of the high sequence homology between the D3R and the dopamine D2 receptor (D2R). In this effort, we synthesized a series of acylaminobutylpiperazines incorporating aza-aromatic units and evaluated their binding and functional activities at the D3 and D2 receptors. Docking studies and results from evaluations against a set of chimeric and mutant receptors suggest that interactions at the extracellular end of TM7 contribute to the D3R versus D2R selectivity of these ligands. Molecular insights from this study could potentially enable rational design of potent and selective D3R ligands. PMID- 25126837 TI - Solution speciation of plutonium and Americium at an Australian legacy radioactive waste disposal site. AB - During the 1960s, radioactive waste containing small amounts of plutonium (Pu) and americium (Am) was disposed in shallow trenches at the Little Forest Burial Ground (LFBG), located near the southern suburbs of Sydney, Australia. Because of periodic saturation and overflowing of the former disposal trenches, Pu and Am have been transferred from the buried wastes into the surrounding surface soils. The presence of readily detected amounts of Pu and Am in the trench waters provides a unique opportunity to study their aqueous speciation under environmentally relevant conditions. This study aims to comprehensively investigate the chemical speciation of Pu and Am in the trench water by combining fluoride coprecipitation, solvent extraction, particle size fractionation, and thermochemical modeling. The predominant oxidation states of dissolved Pu and Am species were found to be Pu(IV) and Am(III), and large proportions of both actinides (Pu, 97.7%; Am, 86.8%) were associated with mobile colloids in the submicron size range. On the basis of this information, possible management options are assessed. PMID- 25126838 TI - Cyclodextrins and surfactants in aqueous solution above the critical micelle concentration: where are the cyclodextrins located? AB - Cyclodextrins (CDs) are known to bind surfactant molecules below the surfactant critical micelle concentration (CMC); however, interactions of CDs with surfactant micelles (above the CMC) are not well understood. In particular, direct structural evidence of the location of CDs in the different subphases found in micellar solutions is lacking. We have utilized small-angle neutron scattering (SANS) with contrast matching to probe the localization of alpha cyclodextrin (alpha-CD) and 2-hydroxypropyl-beta-cyclodextrin (HPbeta-CD) in sodium dodecyl sulfate (SDS) micelles in aqueous (D2O) solutions. SANS data from solutions containing either hydrogenated or deuterated surfactants were analyzed by considering three different scenarios pertaining to the localization of cyclodextrin, either all in solution or some in the micelle shell or some in the micelle core, and were simultaneously fitted using the core-shell prolate ellipsoid form factor and the Hansen-Hayter-based structure factor. The scenario that considered a fraction of CD to localize in the micelle core well described the SANS data from both hydrogenated and deuterated SDS-CD-D2O solutions, while the other two scenarios did not. Among the various structural and interaction parameters obtained from this analysis, it emerged that the micelle core consisted of up to ~10% HPbeta-CD or ~16% alpha-CD with respect to the total number of molecules (surfactants and CDs) present in the micelle at 25 mM SDS, and up to 14% HPbeta-CD or 28% alpha-CD at 50 mM SDS. This is the first study that provides direct evidence on the location of cyclodextrin in the core of surfactant micelles. An improved understanding of CD interactions with surfactants and lipids would enable better strategies for drug encapsulation and delivery with CDs. PMID- 25126839 TI - Incidence and trends of blastomycosis-associated hospitalizations in the United States. AB - We used the State Inpatient Databases from the United States Agency for Healthcare Research and Quality to provide state-specific age-adjusted blastomycosis-associated hospitalization incidence throughout the entire United States. Among the 46 states studied, states within the Mississippi and Ohio River valleys had the highest age-adjusted hospitalization incidence. Specifically, Wisconsin had the highest age-adjusted hospitalization incidence (2.9 hospitalizations per 100,000 person-years). Trends were studied in the five highest hospitalization incidence states. From 2000 to 2011, blastomycosis associated hospitalizations increased significantly in Illinois and Kentucky with an average annual increase of 4.4% and 8.4%, respectively. Trends varied significantly by state. Overall, 64% of blastomycosis-associated hospitalizations were among men and the median age at hospitalization was 53 years. This analysis provides a complete epidemiologic description of blastomycosis-associated hospitalizations throughout the endemic area in the United States. PMID- 25126840 TI - Parasite pressures on feral honey bees (Apis mellifera sp.). AB - Feral honey bee populations have been reported to be in decline due to the spread of Varroa destructor, an ectoparasitic mite that when left uncontrolled leads to virus build-up and colony death. While pests and diseases are known causes of large-scale managed honey bee colony losses, no studies to date have considered the wider pathogen burden in feral colonies, primarily due to the difficulty in locating and sampling colonies, which often nest in inaccessible locations such as church spires and tree tops. In addition, little is known about the provenance of feral colonies and whether they represent a reservoir of Varroa tolerant material that could be used in apiculture. Samples of forager bees were collected from paired feral and managed honey bee colonies and screened for the presence of ten honey bee pathogens and pests using qPCR. Prevalence and quantity was similar between the two groups for the majority of pathogens, however feral honey bees contained a significantly higher level of deformed wing virus than managed honey bee colonies. An assessment of the honey bee race was completed for each colony using three measures of wing venation. There were no apparent differences in wing morphometry between feral and managed colonies, suggesting feral colonies could simply be escapees from the managed population. Interestingly, managed honey bee colonies not treated for Varroa showed similar, potentially lethal levels of deformed wing virus to that of feral colonies. The potential for such findings to explain the large fall in the feral population and the wider context of the importance of feral colonies as potential pathogen reservoirs is discussed. PMID- 25126841 TI - The complete genome sequence of Escherichia coli EC958: a high quality reference sequence for the globally disseminated multidrug resistant E. coli O25b:H4-ST131 clone. AB - Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum beta-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage. PMID- 25126843 TI - Trochlear groove osteochondritis dissecans of the knee patellofemoral joint. AB - BACKGROUND: The trochlear groove is the rarest location for osteochondritis dissecans (OCD) of the knee, with only about 50 previously reported cases, most of which were treated before the advent of magnetic resonance imaging (MRI) and modern techniques of cartilage fixation or osteochondral transplantation. The purpose of this multicenter study was to assess the patient presentation and clinical, radiographic, and functional results of treatment for trochlear groove OCD lesions. METHODS: Hospital records from 5 institutions of the Research in Osteochondritis of the Knee (ROCK) study group were retrospectively reviewed for cases of trochlear groove OCD. Demographics, clinical presentation, diagnosis, treatment, time to pain resolution, and return to sports were recorded. Lesion appearance, size, stability, and time to radiographic healing were evaluated on plain x-rays and MRIs. RESULTS: Trochlear groove OCD lesions were evaluated in 24 knees in 21 adolescents (17 male, 4 female), with an average age of 14 years (range, 10 to 18 y). Fifty-four percent (13/24) of the lesions were identifiable on radiographs, and all were identifiable on MRI, 38% of which (9/24) was unstable. One fourth (6/24) of knees had coexistent femoral condyle OCD lesions. Treatment outcomes were evaluated in patients with a minimum of 1-year follow-up (average: 3 y; range: 1 to 12 y) or healing before 1 year. Half of the knees (2/4) treated nonoperatively and two thirds (8/12) treated operatively showed radiographic signs of healing with patients returning to full activity without pain. Operative treatment success rates were as follows: drilling (3/3), fixation (3/3), microfracture (1/2), drilling with subsequent delayed microfracture (1/1), and drilling with fixation (0/3). CONCLUSIONS: MRI aids in the diagnosis and staging of trochlear groove OCD lesions, as almost one half may not be identifiable on radiographs, and one quarter are associated with OCD lesions in other locations of the same knee. Multiple operative treatments can be used to achieve healing or resolution of symptoms in stable and unstable lesions; however, a larger comparative study is needed to make specific recommendations. LEVEL OF EVIDENCE: Therapeutic Level IV. PMID- 25126842 TI - Promiscuous speciation with gene flow in silverside fish genus Odontesthes (Atheriniformes, Atherinopsidae) from south western Atlantic Ocean basins. AB - The present paper integrates phylogenetic and population genetics analyses based on mitochondrial and nuclear molecular markers in silversides, genus Odontesthes, from a non-sampled area in the SW Atlantic Ocean to address species discrimination and to define Managements Units for sustainable conservation. All phylogenetic analyses based on the COI mitochondrial gene were consistent to support the monophyly of the genus Odontesthes and to include O. argentinensis, O. perugiae-humensis and some O. bonariensis haplotypes in a basal polytomy conforming a major derivative clade. Microsatellites data revealed somewhat higher genetic variability values in the O. argentinensis-perugia populations than in O. bonariensis and O. perugia-humensis taxa. Contrasting population genetics structuring emerged from mitochondrial and microsatellites analyses in these taxa. Whereas mitochondrial data supported two major groups (O. argentinensis-perugia-humensis vs. O. bonariensis-perugiae-humensis populations), microsatellite data detected three major genetic entities represented by O. bonariensis, O. perugiae-humensis and an admixture of populations belonging to O. argentinensis-perugiae respectively. Therefore, the star COI polytomy in the tree topology involving these taxa could be interpreted by several hypothetic scenarios such as the existence of shared ancestral polymorphisms, incomplete lineage sorting in a radiating speciation process and/or reticulation events. Present findings support that promiscuous and recent contact between incipient species sharing asymmetric gene flow exchanges, blurs taxa boundaries yielding complicated taxonomy and Management Units delimitation in silverside genus Odontesthes from SW Atlantic Ocean basins. PMID- 25126844 TI - Upper thoracic pedicle screws loss of fixation causing spinal cord injury. PMID- 25126846 TI - Highly informative single-copy nuclear microsatellite DNA markers developed using an AFLP-SSR approach in black spruce (Picea mariana) and red spruce (P. rubens). AB - BACKGROUND: Microsatellites or simple sequence repeats (SSRs) are highly informative molecular markers for various biological studies in plants. In spruce (Picea) and other conifers, the development of single-copy polymorphic genomic microsatellite markers is quite difficult, owing primarily to the large genome size and predominance of repetitive DNA sequences throughout the genome. We have developed highly informative single-locus genomic microsatellite markers in black spruce (Picea mariana) and red spruce (Picea rubens) using a simple but efficient method based on a combination of AFLP and microsatellite technologies. PRINCIPAL FINDINGS: A microsatellite-enriched library was constructed from genomic AFLP DNA fragments of black spruce. Sequencing of the 108 putative SSR-containing clones provided 94 unique sequences with microsatellites. Twenty-two of the designed 34 primer pairs yielded scorable amplicons, with single-locus patterns. Fourteen of these microsatellite markers were characterized in 30 black spruce and 30 red spruce individuals drawn from many populations. The number of alleles at a polymorphic locus ranged from 2 to 18, with a mean of 9.3 in black spruce, and from 3 to 15, with a mean of 6.2 alleles in red spruce. The polymorphic information content or expected heterozygosity ranged from 0.340 to 0.909 (mean = 0.67) in black spruce and from 0.161 to 0.851 (mean = 0.62) in red spruce. Ten SSR markers showing inter-parental polymorphism inherited in a single-locus Mendelian mode, with two cases of distorted segregation. Primer pairs for almost all polymorphic SSR loci resolved microsatellites of comparable size in Picea glauca, P. engelmannii, P. sitchensis, and P. abies. SIGNIFICANCE: The AFLP-based microsatellite-enriched library appears to be a rapid, cost-effective approach for isolating and developing single-locus informative genomic microsatellite markers in black spruce. The markers developed should be useful in black spruce, red spruce and other Picea species for various genetics, genomics, breeding, forensics, conservation studies and applications. PMID- 25126848 TI - A viable population of the European red squirrel in an urban park. AB - Whether urban parks can maintain viable and self-sustaining populations over the long term is questionable. In highly urbanized landscapes, urban parks could play a role in biodiversity conservation by providing habitat and resources to native species. However, populations inhabiting urban parks are usually small and isolated, leading to increased demographic stochasticity and genetic drift, with expected negative consequences on their viability. Here, we investigated a European red squirrel population located in an urban park close to Paris, France (Parc de Sceaux; 184 ha) to assess its viability. Using mitochondrial D-loop sequences and 13 microsatellite loci, we showed that the population presented high levels of genetic variation and no evidence of inbreeding. The size of the population was estimated at 100-120 individuals based on the comparison of two census techniques, Distance Sampling and Capture-Mark-Recapture. The estimated heterozygosity level and population size were integrated in a Population Viability Analysis to project the likelihood of the population's persistence over time. Results indicate that the red squirrel population of this urban park can be viable on the long term (i.e. 20 years) for a range of realistic demographic parameters (juvenile survival at least >40%) and immigration rates (at least one immigration event every two years). This study highlights that urban parks can be potential suitable refuges for the red squirrel, a locally threatened species across western European countries, provided that ecological corridors are maintained. PMID- 25126847 TI - A quest for miRNA bio-marker: a track back approach from gingivo buccal cancer to two different types of precancers. AB - Deregulation of miRNA expression may contribute to tumorigenesis and other patho physiology associated with cancer. Using TLDA, expression of 762 miRNAs was checked in 18 pairs of gingivo buccal cancer-adjacent control tissues. Expression of significantly deregulated miRNAs was further validated in cancer and examined in two types of precancer (leukoplakia and lichen planus) tissues by primer specific TaqMan assays. Biological implications of these miRNAs were assessed bioinformatically. Expression of hsa-miR-1293, hsa-miR-31, hsa-miR-31* and hsa miR-7 were significantly up-regulated and those of hsa-miR-206, hsa-miR-204 and hsa-miR-133a were significantly down-regulated in all cancer samples. Expression of only hsa-miR-31 was significantly up-regulated in leukoplakia but none in lichen planus samples. Analysis of expression heterogeneity divided 18 cancer samples into clusters of 13 and 5 samples and revealed that expression of 30 miRNAs (including the above-mentioned 7 miRNAs), was significantly deregulated in the cluster of 13 samples. From database mining and pathway analysis it was observed that these miRNAs can significantly target many of the genes present in different cancer related pathways such as "proteoglycans in cancer", PI3K-AKT etc. which play important roles in expression of different molecular features of cancer. Expression of hsa-miR-31 was significantly up-regulated in both cancer and leukoplakia tissues and, thus, may be one of the molecular markers of leukoplakia which may progress to gingivo-buccal cancer. PMID- 25126849 TI - Financial costs of large carnivore translocations--accounting for conservation. AB - Human-carnivore conflict continues to present a major conservation challenge around the world. Translocation of large carnivores is widely implemented but remains strongly debated, in part because of a lack of cost transparency. We report detailed translocation costs for three large carnivore species in Namibia and across different translocation scenarios. We consider the effect of various parameters and factors on costs and translocation success. Total translocation cost for 30 individuals in 22 events was $80,681 (US Dollars). Median translocation cost per individual was $2,393, and $2,669 per event. Median cost per cheetah was $2,760 (n = 23), and $2,108 per leopard (n = 6). One hyaena was translocated at a cost of $1,672. Tracking technology was the single biggest cost element (56%), followed by captive holding and feeding. Soft releases, prolonged captivity and orphaned individuals also increased case-specific costs. A substantial proportion (65.4%) of the total translocation cost was successfully recovered from public interest groups. Less than half the translocations were confirmed successes (44.4%, 3 unknown) with a strong species bias. Four leopards (66.7%) were successfully translocated but only eight of the 20 cheetahs (40.0%) with known outcome met these strict criteria. None of the five habituated cheetahs was translocated successfully, nor was the hyaena. We introduce the concept of Individual Conservation Cost (ICC) and define it as the cost of one successfully translocated individual adjusted by costs of unsuccessful events of the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard. Translocations are costly, but we demonstrate that they are not inherently more expensive than other strategies currently employed in non-lethal carnivore conflict management. We conclude that translocation should be one available option for conserving large carnivores, but needs to be critically evaluated on a case-by-case basis. PMID- 25126852 TI - Mapping and introgression of QTL involved in fruit shape transgressive segregation into 'piel de sapo' melon (cucumis melo l.) [corrected]. AB - A mapping F2 population from the cross 'Piel de Sapo' * PI124112 was selectively genotyped to study the genetic control of morphological fruit traits by QTL (Quantitative Trait Loci) analysis. Ten QTL were identified, five for FL (Fruit Length), two for FD (Fruit Diameter) and three for FS (Fruit Shape). At least one robust QTL per character was found, flqs8.1 (LOD = 16.85, R2 = 34%), fdqs12.1 (LOD = 3.47, R2 = 11%) and fsqs8.1 (LOD = 14.85, R2 = 41%). flqs2.1 and fsqs2.1 cosegregate with gene a (andromonoecious), responsible for flower sex determination and with pleiotropic effects on FS. They display a positive additive effect (a) value, so the PI124112 allele causes an increase in FL and FS, producing more elongated fruits. Conversely, the negative a value for flqs8.1 and fsqs8.1 indicates a decrease in FL and FS, what results in rounder fruits, even if PI124112 produces very elongated melons. This is explained by a significant epistatic interaction between fsqs2.1 and fsqs8.1, where the effects of the alleles at locus a are attenuated by the additive PI124112 allele at fsqs8.1. Roundest fruits are produced by homozygous for PI124112 at fsqs8.1 that do not carry any dominant A allele at locus a (PiPiaa). A significant interaction between fsqs8.1 and fsqs12.1 was also detected, with the alleles at fsqs12.1 producing more elongated fruits. fsqs8.1 seems to be allelic to QTL discovered in other populations where the exotic alleles produce elongated fruits. This model has been validated in assays with backcross lines along 3 years and ultimately obtaining a fsqs8.1-NIL (Near Isogenic Line) in 'Piel de Sapo' background which yields round melons. PMID- 25126851 TI - Large-scale, high-resolution multielectrode-array recording depicts functional network differences of cortical and hippocampal cultures. AB - Understanding the detailed circuitry of functioning neuronal networks is one of the major goals of neuroscience. Recent improvements in neuronal recording techniques have made it possible to record the spiking activity from hundreds of neurons simultaneously with sub-millisecond temporal resolution. Here we used a 512-channel multielectrode array system to record the activity from hundreds of neurons in organotypic cultures of cortico-hippocampal brain slices from mice. To probe the network structure, we employed a wavelet transform of the cross correlogram to categorize the functional connectivity in different frequency ranges. With this method we directly compare, for the first time, in any preparation, the neuronal network structures of cortex and hippocampus, on the scale of hundreds of neurons, with sub-millisecond time resolution. Among the three frequency ranges that we investigated, the lower two frequency ranges (gamma (30-80 Hz) and beta (12-30 Hz) range) showed similar network structure between cortex and hippocampus, but there were many significant differences between these structures in the high frequency range (100-1000 Hz). The high frequency networks in cortex showed short tailed degree-distributions, shorter decay length of connectivity density, smaller clustering coefficients, and positive assortativity. Our results suggest that our method can characterize frequency dependent differences of network architecture from different brain regions. Crucially, because these differences between brain regions require millisecond temporal scales to be observed and characterized, these results underscore the importance of high temporal resolution recordings for the understanding of functional networks in neuronal systems. PMID- 25126853 TI - Erasing the past: a new identity for the Damoclean pathogen causing South American leaf blight of rubber. AB - BACKGROUND: South American leaf blight (SALB) of rubber has been the main constraint to production in its neotropical centre of origin since commercial plantations were first established. The fungal causal agent was identified and described more than a century ago but its precise placement within the Ascomycota still remains uncertain. Indeed, such is the ambiguity surrounding the pathogen that each of the spore morphs would, according to their present classification, be placed in different ascomycete families: the Microcyclus sexual morph in the Planistromellaceae and the two purported asexual morphs--Fusicladium and Aposphaeria--in the Venturiaceae and Lophiostomataceae, respectively. Given the historical importance of the fungus and the ever-menacing threat that it poses to rubber production in the Palaeotropics--and, thus to the rubber industry and to the global economy--its phylogeny, as well as its biology, should be resolved as a matter of urgency. METHODS AND RESULTS: Here, six genomic regions (LSU rRNA, mtSSU, MCM7, EF-1alpha, Act and ITS) were used for reconstructing the molecular phylogeny of the SALB fungus based on material collected throughout Brazil. The analyses support the classification of the fungus in the family Mycosphaerellaceae s. str. (Capnodiales, Dothideomycetes) and place it firmly within the clade Pseudocercospora s. str., now accepted as one of the distinct genera within Mycosphaerellaceae. The new combination Pseudocercospora ulei is proposed and the life cycle of the fungus is confirmed, based on both experimental and phylogenetic evidence, with the Aposphaeria morph shown to have a spermatial rather than an infective-dispersal function. CONCLUSIONS: Because the phylogeny of the SALB fungus has now been clarified, new insights of its epidemiology and genomics can be gained following comparison with closely related, better-researched crop pathogens. PMID- 25126854 TI - Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine manufactured with and without polysorbate 80 given to healthy infants at 2, 3, 4 and 12 months of age. AB - BACKGROUND: Polysorbate 80 (P80), a nonionic detergent used to solubilize proteins, is used in both oral and injectable medications including vaccines. Development studies with 13-valent pneumococcal conjugate vaccine (PCV13) showed that adding P80 resulted in a more robust manufacturing process. Before adding P80 to the formulation of PCV13, we investigated the immunogenicity and safety of PCV13 with and without P80. METHODS: Phase 3, parallel-group, randomized, active controlled, double-blind multicenter trial was conducted at 15 sites in Poland. Healthy infants were randomized (1:1) to receive PCV13+P80 or PCV13 without P80 given at ages 2, 3, 4 and 12 months concomitantly with DTaP-IPV-Hib at 2, 3 and 4 months; hepatitis B at 2 months and measles, mumps, and rubella at 12 months. Serotype-specific antipneumococcal immune responses were evaluated using antipolysaccharide capsular immunoglobulin (Ig)G responses and opsonophagocytic activity (OPA) assay. Safety data were also collected. RESULTS: The 2 treatment groups were demographically similar. Following the infant immunization series, anticapsular IgG antibody geometric mean concentrations and OPA geometric mean titers for each serotype were within 2-fold between the 2 groups. Formal noninferiority criteria for comparison of proportion of responders (subjects with IgG titers >=0.35 MUg/mL) were met for 11 of the 13 serotypes. Overall population responses were highly similar. Anticapsular IgG responses were also within 2-fold following the toddler dose. Safety profiles were similar between the 2 groups. CONCLUSIONS: Addition of P80 to PCV13 did not adversely affect PCV13 immunogenicity or safety when compared with vaccine formulated without P80. PMID- 25126855 TI - Human parechovirus infection in neonatal intensive care. AB - BACKGROUND: Approximately 5-6% of all infective episodes in neonatal intensive care unit (NICU) are of viral origin. Previous studies suggest that human parechovirus (HPeV) infection presents most commonly in term infants, as a sepsis like syndrome in which meningoencephalitis is prominent. Our aim was to study the infection rate and associated features of HPeV. METHODS: Blood samples were taken from NICU babies older than 48 hours, who were being investigated for late onset sepsis. Clinical and laboratory data were collected at the time of the suspected sepsis episode. Samples were tested using universal primers and probe directed at the 5'-untranslated region of the HPeV genome by reverse transcriptase polymerase chain reaction (RT-PCR). Results were confirmed by electrophoresis and DNA sequencing. RESULTS: HPeV was detected in 11 of 84 samples (13%). These infants had a mean [interquartile range (IQR)] gestational age of 28.9 (26.9-30.6) weeks and mean birth weight of 1.26 (SD = 0.72) kg. The median day of presentation was 16 (IQR: 11-27). These characteristics were similar to the infants without positive viral detection. Six infants presented with respiratory signs. One infant presented with signs of meningitis. Six of the 11 episodes of HPeV infection occurred during the winter months (December to February). No HPeV positive infants had abnormal findings on their 28-day cranial ultrasound examination. CONCLUSIONS: We found an HPeV infection rate of 13% in infants being tested for late onset sepsis. HPeV should be considered as a possible cause of sepsis-like symptoms in preterm infants. PMID- 25126856 TI - Clinical profile and predictors of fatal Rocky Mountain spotted fever in children from Sonora, Mexico. AB - BACKGROUND: Rocky Mountain spotted fever (RMSF) is an increasingly important cause of preventable mortality in children in Sonora, Mexico. Although early treatment with tetracycline has shown to prevent fatal outcome, the disease remains a life-threatening condition, particularly for children. This study describes the clinical factors associated with pediatric mortality due to RMSF in Sonora, in order to guide healthcare practices. METHODS: This is a retrospective analysis of 104 children consecutively hospitalized at the major pediatric hospital of Sonora, diagnosed with RMSF between January 2004 and December 2013. Descriptive statistics and multiple logistic regression were used to identify risk factors for fatal outcome. RESULTS: The case fatality ratio in this cohort was 20.2%. Children were hospitalized after a median of 6 days from onset of symptoms including fever (100%), rash involving palms and soles (88.5%) and headache (79.8%); 90.4% of fatal cases had low platelet counts (<50,000/MUL) and 33.3% showed serum creatinine concentrations above the normal value. Acute kidney injury increased mortality, odds ratio (OR(adj)) = 4.84, 95% confidence interval (CI): 1.2-16.2, as well as delay in treatment (>= 5th day from onset) with doxycycline, OR(adj) = 2.62, 95% CI: 1.24-5.52 and hemorrhage, OR(adj) = 6.11, 95% CI: 1.89-19.69. CONCLUSIONS: RMSF is a public health problem in Sonora. Clinically, fatal cases differ from non-fatal cases in renal function and hemorrhagic manifestations, although these findings may occur too late for a timely intervention. First-line providers must be educated to harbor a timely suspicion of RMSF, and should provide empiric treatment with doxycycline when febrile patients first present for care. PMID- 25126857 TI - Fatal human bocavirus infection in an 18-month-old child with chronic lung disease of prematurity. AB - A fatal case of human bocavirus 1 pulmonary infection in an 18-month-old prematurely born child is described. Despite conventional and oscillatory ventilatory support, intractable hyperinflation developed with bilateral pneumothorax and acute cardiac failure 3 days after the onset of respiratory symptoms. PMID- 25126858 TI - Implicit learning in individuals with autism spectrum disorders: a meta-analysis. AB - BACKGROUND: Individuals with autism spectrum disorders (ASDs) are characterized by social communication difficulties and behavioural rigidity. Difficulties in learning from others are one of the most devastating features of this group of conditions. Nevertheless, the nature of learning difficulties in ASDs is still unclear. Given the relevance of implicit learning for social and communicative functioning, a link has been hypothesized between ASDs and implicit learning deficit. However, studies that have employed formal testing of implicit learning in ASDs provided mixed results. METHOD: We undertook a systematic search of studies that examined implicit learning in ASDs using serial reaction time (SRT), alternating serial reaction time (ASRT), pursuit rotor (PR), and contextual cueing (CC) tasks, and synthesized the data using meta-analysis. A total of 11 studies were identified, representing data from 407 individuals with ASDs and typically developing comparison participants. RESULTS: The results indicate that individuals with ASDs do not differ in any task considered [SRT and ASRT task: standardized mean difference (SMD) -0.18, 95% confidence interval (CI) -0.71 to 0.36; PR task: SMD -0.34, 95% CI -1.04 to 0.36; CC task: SMD 0.27, 95% CI -0.07 to 0.60]. CONCLUSIONS: Based on our synthesis of the existing literature, we conclude that individuals with ASDs can learn implicitly, supporting the hypothesis that implicit learning deficits do not represent a core feature in ASDs. PMID- 25126859 TI - Solution processed n-In2O3 nanostructures for organic-inorganic hybrid p-n junctions. AB - Solution processed organic-inorganic bulk hybrid heterostructures are nowadays considered as the most promising elements to perform efficient optoelectronic functions. In this regard, In2O3 based hybrid heterostructures were fabricated using polypyrrole and their role as efficient interfacial layers was studied using polypyrrole/ZnO nanowires. The In2O3 nanostructures were synthesized through a facile wet chemical approach at an average scale of less than 10 nm in cubic phase. The presence of O and In related defects was studied through emission spectra; these were also found to exhibit their predominance in Raman measurements. The n-type characteristics and donor density value of around 10(20) cm(-3) were evaluated for the In2O3 specimens via Mott-Schottky plots. The role of In2O3 nanostructures as active/interfacial layers was then studied using the current-voltage characteristics obtained across the hybrid heterostructures made of polypyrrole/In2O3, polypyrrole/ZnO and polypyrrole/In2O3/ZnO. Organic inorganic p-n diodes were obtained via in situ chemical polymerization, drop casting and hydrothermal routes. Cyclic voltammograms and Nyquist plots were used to study the reduction mechanism taking place in the nanostructures that actually results with the formation of metallic In, which plays a vital role in establishing the required conduction electrons. The same has been reasoned for the improved rectification characteristics observed across the diodes. PMID- 25126860 TI - Regulation of insulin sensitivity by adiponectin and its receptors in response to physical exercise. AB - Adiponectin is an adipocyte-derived abundant plasma protein, also called Acrp30 (adipocyte complement-related protein), adipoQ, ApM1 (AdiPose Most abundant Gene transcript 1), or GBP28 (gelatin-binding protein-28). Insulin resistance is a primary contributing factor in the pathogenesis of type 2 diabetes. Adiponectin binds to adiponectin receptors AdipoR1 and AdipoR2, and exerts antidiabetic effects via activation of AMPK and PPAR-alpha pathways, respectively. In the same sense chronic exercise has been showed to induce numerous metabolic factors that can improve insulin resistance. It has been reported that physical exercise training increases adiponectin receptors, which may mediate the improvement of insulin resistance in response to exercise, which is the focus of the present review. PMID- 25126861 TI - Expression analysis of GADD45gamma, MEG3, and p8 in pituitary adenomas. AB - Preceding studies have indicated that aberrant expression levels rather than genetic changes of GADD45gamma, MEG3, and p8 gene might play a role in the pathogenesis of pituitary adenomas. We analysed their expression in various normal human tissues and in different pituitary tumour types, and investigated GADD45gamma mutations in a subset of adenomas. Absolute quantification by real time RT-PCR was performed in 24 normal tissues as well as in 34 nonfunctioning, 24 somatotroph, 12 corticotroph adenomas, 4 prolactinomas, 1 FSHoma, and in 6 normal pituitaries. Furthermore, we investigated the relationship between clinical data and gene expression. A subset was screened for GADD45gamma mutations by single strand conformation polymorphism analysis (SSCP) and sequencing. All normal human tissues expressed GADD45gamma, MEG3, and p8 mRNA. For GADD45gamma, significantly lower expression levels were found in nonfunctioning adenomas compared with normal pituitary and somatotroph adenomas. P8 and MEG3 mRNA levels were significantly lower in nonfunctioning and corticotroph adenomas compared with normal pituitary. Expression of GADD45gamma was significantly higher in pituitary adenomas of female patients. No mutation was found in the GADD45gamma gene. GADD45gamma, MEG3, and p8 appear to have physiological functions in a variety of human tissues. GADD45gamma, MEG3, and P8 may be involved in the pathogenesis of nonfunctioning and corticotroph pituitary tumours. Female gender seems to predispose to slightly higher GADD45gamma expression in pituitary adenomas. Mutations of the GADD45gamma are unlikely to be involved in the pathogenesis of pituitary adenomas. PMID- 25126863 TI - Awareness, perception and coverage of tetanus immunisation in women of child bearing age in an urban district of Lagos, Nigeria. AB - AIMS AND OBJECTIVES: This study assessed the level of awareness and perception of women of child bearing age to tetanus immunisation and determines the cover- age rate in Ojodu Local Council Development Area (LCDA) of Lagos State, Nigeria. SUBJECTS AND METHODS: This is a descriptive cross-sectional study of 288 women of child bearing age selected using multistage sampling technique. Information was obtained using structured close-ended questionnaire. Data analysis was done using Epi-InfoTM software, version 3.5.1. RESULTS: There was high level of awareness of tetanus immunisation among respondents (89%) and as a method of prevention of tetanus (76%). There was a positive association between the level of awareness and respondents' educational level and occupation (p < 0.05). However, there is a low level of awareness regarding the number of doses of the vaccine required in pregnancy(14.4%) and for life protection (19.5%). Those who ever received the vaccine,got it post-injury (48.9%) and in pregnancy (45.2%). Age, occupation and parity were positively associated with receiving the vaccine (p < 0.05), while parity and marital status were positively associated with number of dose of vaccine received (p < 0.05). Only about 20% of the respondents had received two or more doses of the vaccine. CONCLUSION: This study concludes that despite the high level of awareness about tetanus and tetanus immunisation, there is a low coverage rate of tetanus immunisation among women of child bearing age in Ojodu LCDA of Lagos State. Women of child bearing age should also be targeted at the community level in tetanus immunisation campaign programme. PMID- 25126864 TI - A cross-sectional study for algorithm in diagnosing simple uncomplicated malaria in children in health facilities without laboratory backup in Nigeria. AB - AIMS AND OBJECTIVES: The objective of this study was to determine an algorithm for malaria diagnosis using presenting signs and symptoms of children (aged 0-13 years) with uncomplicated malaria in Gwagwalada Area Council of Abuja, Nigeria. MATERIALS AND METHODS: A validated questionnaire was used to obtain relevant data from 400 children diagnosed presumptively of simple malaria by clinicians and 400 other children of similar sex and age considered as not having malaria. Giemsa stained thick blood films were used to determine parasitaemia. Data obtained was analysed using Epi-Info version 3.3.2. RESULTS: Thirty-eight per cent of children with presumptive diagnosis of malaria had parasitaemia. Fever, rigor, vomiting, jaundice, pallor and spleen enlargement had significant statistical relationship with parasitaemia on bivariate analysis, but only fever (p=0.00), rigor (p=0.00), vomiting (p=0.00), and pallor (p=0.00) maintained the relationship when subjected to logistic regression analysis. But these symptoms individually had low sensitivity and/or specificity. Candidate algorithms (combinations of symptoms) were then successively subjected to bivariate, logistic and validity analyses. Fever with vomiting gave the highest sensitivity (56.2%), specificity (76.4%) and PPV (60.0%) and were therefore adopted as the algorithm of choice. CONCLUSION AND RECOMMENDATIONS: Children presenting with fever and vomiting without any other obvious cause in health facilities without laboratory support in the research area should receive antimalarial treatment, to help reduce the malaria scourge. This algorithm should be field-tested and if found reliable should be adopted to ease the problem of malaria diagnosis in peripheral health facilities. PMID- 25126862 TI - Delivery of full-length factor VIII using a piggyBac transposon vector to correct a mouse model of hemophilia A. AB - Viral vectors have been used for hemophilia A gene therapy. However, due to its large size, full-length Factor VIII (FVIII) cDNA has not been successfully delivered using conventional viral vectors. Moreover, viral vectors may pose safety risks, e.g., adverse immunological reactions or virus-mediated cytotoxicity. Here, we took advantages of the non-viral vector gene delivery system based on piggyBac DNA transposon to transfer the full-length FVIII cDNA, for the purpose of treating hemophilia A. We tested the efficiency of this new vector system in human 293T cells and iPS cells, and confirmed the expression of the full-length FVIII in culture media using activity-sensitive coagulation assays. Hydrodynamic injection of the piggyBac vectors into hemophilia A mice temporally treated with an immunosuppressant resulted in stable production of circulating FVIII for over 300 days without development of anti-FVIII antibodies. Furthermore, tail-clip assay revealed significant improvement of blood coagulation time in the treated mice. piggyBac transposon vectors can facilitate the long-term expression of therapeutic transgenes in vitro and in vivo. This novel gene transfer strategy should provide safe and efficient delivery of FVIII. PMID- 25126865 TI - The effect of a sexuality education programme among out- of- school adolescents in Lagos, Nigeria. AB - AIMS AND OBJECTIVES: This study was conducted to assess the effect of a community based sexuality education programme on the sexual health knowledge and practices of out of school female adolescents. SUBJECTS AND METHODS: This Intervention study was conducted in two markets within Lagos, Nigeria. Representative samples of adolescents were interviewed on their sexual health knowledge and practices. An Education- entertainment programme provided sexuality education to adolescents in Mushin market only (intervention group) followed by post intervention surveys in Mushin market and Sangrouse market (control group). The pre and post intervention surveys were compared 6 months post intervention to detect any changes. RESULTS: Sexual health knowledge and behaviour was similar among respondents in both markets pre intervention. Post intervention, the sexual health knowledge of the respondents in the intervention site improved significantly. (p<0.05) Fewer adolescents initiated sex in the intervention site than in the control site and contraceptive use increased. However among the sexually active, there was no significant change in their condom use and number of sexual partners. CONCLUSION: Community based health education programmes can be used to provide effective sexuality education for out of school adolescents. Provision should be made by government and non-governmental organisations during adolescent reproductive health programming for sexuality education targeted at out of school adolescents. PMID- 25126866 TI - The effect of a short anti-smoking awareness programme on the knowledge, attitude and practice of cigarette smoking among secondary school students in Lagos state, Nigeria. AB - This study aimed to assess the effect of a short school-based anti-smoking program on the knowledge, attitude and practice of cigarette smoking among students in secondary schools in Lagos State. SUBJECTS AND METHODS: A non randomized, controlled intervention study was done among respondents selected using multi-stage sampling. Baseline data was collected using self-administered questionnaires. An anti-smoking awareness programme was carried out among students in the intervention group using health talks, information leaflets and posters. Post-intervention data collection took place three months later. RESULTS: There were significant increments in the mean knowledge and attitude scores after the intervention. There was however no statistically significant change in the current smoking habits of respondents (4% vs. 3%; p=0.41)in the intervention group. Nevertheless, in the intervention group, the number of never- smokers who reported that they were likely to initiate cigarette smoking within the next year significantly reduced. There was also a significant increase in the proportion of current smokers who desired to quit smoking. CONCLUSION: Even brief anti-smoking programs of this nature are effective at improving the knowledge and modifying the attitude of the respondents but do not improve smoking habits. It however motivated the desire to quit among current smokers. Health education sessions and periodic anti-smoking programmes should be introduced into the secondary school curriculum. More intensive approaches may be needed to influence the smoking behaviour of adolescent smokers. PMID- 25126867 TI - Effects of interval exercise training programme on the indices of adiposity and biomarker of inflammation in hypertension: a randomised controlled trial. AB - AIMS AND OBJECTIVES: Hypertension remains a significant risk factor in cardiovascular morbidity and mortality. The purpose of the present study was to investigate the effects of 8 weeks interval training programme on blood pressure, aerobic capacity (VO max), indices of adiposity and marker of inflammation in black African men with essential hypertension. PATIENTS AND METHODS: Two hundred and forty five (245) male subjects with stage 1 and 2 (systolic blood pressure [SBP] between 140-179 & diastolic blood pressure [DBP] between 90-109 mmHg) essential hypertension were age matched and grouped into experimental and control groups. The experimental (n=140; 58.90 +/- 7.35 years) group involved in an 8 weeks interval training (60-79% HRmax) programme of between 45 and 60 minutes, while age-matched control hypertensive (n=105; 58.27+/-6.24 years) group remain sedentary during this period. All subjects in both groups were on antihypertensive drugs throughout the study period. Cardiovascular parameters (SBP, DBP) & VO max and percent body fat [%BF], waist to hip ratio [WHR] and C reactive protein [CRP] were assessed. Independent t-test and Pearson correlation test were used in data analysis. RESULTS: Findings of the study revealed significant decreased effects of interval training programme on SBP, DBP, %BF, WHR and CRP and significant increased effect on VO max at p< 0.05. Also, changes in CRP as a result of exercise training significantly and positively correlated with changes in SBP, DBP, %BF, WHR, CRP and negatively correlated with VO max at p< 0.05. PMID- 25126868 TI - The knowledge and attitude of non-ophthalmic medical doctors towards glaucoma in two tertiary institutions in south eastern Nigeria. AB - AIMS AND OBJECTIVES: This study is aimed at determining how much knowledge of glaucoma the non-ophthalmic medical doctors still possess and their personal attitudes toward glaucoma. PATIENTS AND METHODS: Self- administered questionnaires were randomly distributed to the non-ophthalmic medical doctors in two specialist hospitals in south eastern Nigeria: The data obtained were the age, sex, professional and number of years of practice of the participants, their knowledge of the symptoms/ aetiology/risk factors, examination/investigation, treatment of glaucoma as well as their personal attitude towards glaucoma. RESULTS: There were two hundred respondents; one hundred and forty two males and fifty eight females (M:F=2.4:1); comprising 82.5% Resident doctors; 51% of whom had been in practice for less than 5 years.All the doctors had heard of glaucoma; approximately seventy two per cent (72.5%) had a good knowledge of glaucoma symptoms and 52.0% of these had been in practice for only 5 years or less. Similarly, of the 83% of the doctors who correctly answered the questions on the aetiology of glaucoma, majority (84.3%) had been in practice for 5 years or less. Only 24.5% and 38.5% respectively of the doctors had a good knowledge of the basic examination and treatment required for the management of glaucoma.There was no statistically significant relationship between most variables tested. Only the relationship between the knowledge of the symptoms of glaucoma and the duration of practice of the doctors was statistically significant (p< 0.005). CONCLUSION: Most of the non-ophthalmic medical doctors have a basic knowledge of glaucoma and how to investigate it but showed a poor knowledge of examination and treatment modalities. They also acknowledged the importance of regular eye checks but only very few had had their eyes examined. PMID- 25126869 TI - Malondialdehyde and antioxidant enzymes in second and third trimesters of pre eclamptic Nigerian women. AB - AIM AND OBJECTIVE: To determine changes in malondialdehyde (product of lipid peroxidation) and antioxidant enzymes (Superoxide Dismutase, Glutathione Per oxidase) levels in pre-eclamptic Nigerian women PATIENTS AND METHODS: A Total of 100 subjects each for pre-eclamptic,apparently normal and non pregnant women were recruited into the study.Venous blood samples were taken from the participants during second and third trimesters of pregnancy and at the point of contact for non pregnant women. Malondialdehyde, glutathione peroxidase and superoxide dismutase were measured accordingly from plasma and haemolysate prepared from whole blood.Variables were analysed using SPSS version 16, taking level of significance to be 0.05 RESULTS: Plasma malondialdehyde in the third trimester (3.13+/-0.61umol/l) of pre-eclamptic subjects was higher than in the second trimester (3.00+/-1.21umol/l).Plasma malondialdehyde in the third trimester of normal pregnancy (2.03+/-0.71umol/l) was also found to be significantly higher than in the second trimester (1.65+/-0.62umol/ l)(p<0.0001). Glutathione peroxidase in pre-eclamptic subjects was significantly higher in the third trimester (2804.11+/-1573.00U/L) as compared to the second trimester (2655.00+/ 1751.30U/L), p= 0.0001.Glutathione peroxidase activity in the third trimester of normal pregnancy(3339.50+/-1733.80U/L) was also found to be higher than in the second trimester(3023.50+/-1115.90U/L)(p=0.131). Superoxide dismutase activity was significantly lower in the third trimester of pre-eclamptic pregnancy when compared to second trimester (110.40+/-59.47 Vs 118.01+/-64.41 U/ ml)(p<0.039) .Similarly,superoxide dismutase activity was significantly lower in the third trimester of normal pregnancy (110.40+/-59.47U/ml) than in the second trimester(153.01+/-71.85U/ml)(p<0.0001). CONCLUSION: There was an increased level of lipid peroxidation products,malondialdehyde in subjects with pre-eclampsia. This was more in the third trimester. There was an increased oxidative stress in pre-eclampsia as evidenced also by low serum level of superoxide dismutase in the third trimester.Diet rich in antioxidant enzyme might be beneficial. PMID- 25126870 TI - Sleep disorders in women attending antenatal care at a tertiary hospital in Nigeria. AB - AIMS AND OBJECTIVES: To determine the prevalence of sleep disorders in a population of Nigerian women during pregnancy and to evaluate the frequency of these sleep disorders according to the three trimesters of pregnancy. SUBJECTS AND METHODS: A prospective cross-sectional design. Participants' were interviewed at the antenatal clinic with a questionnaire to evaluate their sleep during and before pregnancy and to appraise disturbance in their sleep according to the trimester. RESULTS: Two hundred and three pregnant women participated in the survey and were evaluated at one of three points in pregnancy: 1st trimester (n=57), 2nd trimester (n=71) and 3rd trimester (n=75). Overall, the prevalence of sleep disorder in the population surveyed was 35.5% (72/203), more women experienced sleep disturbances in the first (42.1%) and third (40%) trimester of pregnancy compared to the second (25.3%). In terms of types of sleep disorders; 96(47.3%) reported insomnia, 32(15.8%) sleep breathing disorders, 86(42.4%) excessive daytime sleepiness, 172(84.7%) mild sleepiness and 64(31.5%) significant specific awakenings. The most common reason for specific awakening was frequent urination (78.6%). These sleep disorders were more common in the third trimester of pregnancy but only insomnia and specific awakenings showed statistical significance, p=0.007 and 0.031 respectively. Logistic regression model showed that nulliparity, increased BMI and previous adverse obstetric events had significant independent associations with sleep disorders. CONCLUSION: Sleep disorders are common in pregnancy, notably in the first and third trimesters. PMID- 25126871 TI - Asthma control and quality of life in school- age children in Enugu south east, Nigeria. AB - AIMS AND OBJECTIVES: This study set out to assess the quality-of-life of school age children in relation to their level of asthma control. PATIENTS AND METHODS: A cross-sectional descriptive study of children with asthma using the Paediatric Asthma Quality of Life questionnaire (PAQLQ) and the Asthma Therapy Assessment Questionnaire (ATAQ) to respectively assess the health-related quality of life and the level of asthma control. RESULTS: Ninety children with mean age of 11.8(SD, 2.8; 95% CI, 11.2 to 12.4) years, were enrolled. Fifteen children (16.7%) were well-controlled, 17 (18.9%) were partly-controlled while 58 (64.4%) had uncontrolled asthma. The mean asthma control score for all participants was 3.2 (95% CI, 2.8 to 3.7). The mean quality-of-life score was 5.3 (SD, 1.2; 95% CI, 4.9 to 5.5). The lowest score was in the symptom domain: 5.1 (SD, 1.4; 95% CI, 4.9 to 5.5), and among the 14-17 year age group (4.5 SD, 1.5; MD=1.1; p=0.002). The emotional domain was the least affected 5.4 (SD, 1.3; 95% CI, 5.1 to 5.7). Children with well-controlled asthma had the best quality-of-life scores in symptom domains: 5.6 (SD, 1.3; 95% CI, MD=0.6, p=0.63). Quality of life scores were not significant in determining asthma control (MD=0.1, p=0.98). Age was noted as the strongest quality-of-life predictor (B=-0.2, p=0.002). CONCLUSIONS: QOL scores are better in children with well-controlled asthma. Adolescent age group marks a period of both poor asthma control and quality of life in children with asthma. PMID- 25126872 TI - Ultrasonographic spleen size and haematological parameters in children with sickle cell anaemia in Kano, Nigeria. AB - AIMS AND OBJECTIVES: To determine spleen size using abdominal ultrasonography and haematological parameters in steady state children with sickle cell anaemia (SCA). SUBJECTS AND METHODS: An analytical case control study of 150 children with SCA in steady state aged 6 months to 15 years was undertaken. Children with HbAA matched for sex and age were used as controls. The spleen sizes of children with SCA and the controls were determined using abdominal ultrasonography. Haematological parameters (RBC, Hb, MCV, MCH, MCHC,WBC, Platelet and Reticulocyte counts) were also assessed. RESULTS: Fifty three children (35.3%) with SCA against 19 children (12.7%)with HbAA had splenomegaly defined as spleen index > 31cm2. among the children with SCA who had splenomegaly, 17 (11.3%) were older than 10 years. None of those above 10 years with HbAA had splenomegaly. The mean values of RBC, Hb, MCV and MCH were significantly lower in children with SCA compared to age- sex matched HbAA controls (p = 0.001, 0.001, 0.15 and 0.016 respectively), while the mean values of MCHC, WBC, platelet and reticulocyte counts were significantly higher in children with SCA than in the HbAA controls (p = 0.022, 0.001, 0.013 and 0.001) respectively. Among the SCA subjects, as spleen index increased from grade II through grade V, the mean values of RBC, Hb, WBC and platelet count significantly decreased (p =0.001, 0.001, 0.032 and 0.007), while the mean value of reticulocyte count significantly increased (p = 0.001). However, with increasing spleen index from grade II to grade V, the mean values of MCV, MCH and MCHC were not significantly different (p = 0.077, 0.741 and 0.995). CONCLUSION: Splenomegaly persists in much older age group in children with SCA and is associated with mild cytopaenia. Spleen size in children with SCA should be assessed using a more sensitive and reliable method of ultrasonography. PMID- 25126873 TI - Elder abuse and neglect in Zaria northern Nigeria. AB - AIMS AND OBJECTIVES: The aim of this study was to determine the nature and extent of elder abuse and neglect among community dwelling elderly in Zaria, Nigeria. SUBJECTS AND METHODS: Community dwelling elderly in Zaria city North-western Nigeria were interviewed;. they were interviewed using a data collecting sheet designed to obtain socio-demographic data and an instrument designed to detect abuse and neglect in the elderly. The data obtained was analysed using Statistical Package for Social Sciences Version 13 for Windows. RESULTS: Three hundred and fifty one elderly people participated in the study out of which 211(60.1%) were females. The mean age of the participants was 73.90 years (95%CI=.72.96-74.84 years) There was no case of physical, financial or psychological abuse. However, 125(35.6%) participants suffered possible neglect in terms of personal care and hygiene. Increasing age, lack of formal education, receiving pension, not having a spouse and self reported poor health status were significantly associated with elder possible neglect in this community. CONCLUSION: Elder abuse was uncommon in this community like in other communities in the developing countries. However, possible neglect of personal care and hygiene of the elderly was common and that might be due to poor economic status of both the elderly and his other caregiver. PMID- 25126874 TI - Clinical usefulness of a timed overnight (8 hours) Urine Albumin (microalbumin) excretion in monitor-ing treatment in benign essential hypertension. AB - AIMS AND OBJECTIVES: This research aims to establish the usefulness of timed over night (8 hours) Urine Albumin(microalbumin) Excretion (UAE), in monitoring therapy in Nigerian patients with benign essential hypertension. SUBJECTS AND METHODS: The study population comprised 40 normotensives/controls, (23 males and 17 females) aged between 20-70 years, with a mean blood pressure 116/75mmHg, 30 well-controlled hypertensive patients, diastolic BP <100mmHg or MAP (mean arterial pressure) = 110mmHg and 30 poorly controlled hypertensive patients, diastolic blood pressure > 100mmHg or MAP >110mmHg.Urine albumin(microalbumin) was determined on the 8 hours overnight urine samples by ELISA method using kit from Randox Laboratories Limited, N.Ireland Cat No. MA 1410. UAE was calculated from the urine albumin concentration, urine volume and collection time. The intra assay precision was determined by running 20 replicates of two kit controls in a single batch. The coefficient of variation was 6.6% at 10.70mg/L and 4.3% at 51.20mg/L. RESULTS: The average UAE in the three groups were as follows: 12:22 +/ 4.65ug/ min, 21.50 +/- 10.5ug/min and 30.10 +/- 24.25 ug/min in the control, well controlled and poorly controlled groups respectively, 12.5% of normotensive subjects, 40% of well controlled and 56.7% of poorly controlled patients were found to have microalbuminuria.The UAE increased significantly with the severity of hypertension (r = 0.32, p<0.001 for control) r = 0.38, p<00.05 for controlled and r = 0.49 p<0.05 for poorly controlled. CONCLUSION: A timed overnight (8 hours) Urinary UAE is a preferred alternative to cumbersome 24 hours urine collection for monitoring response to treatment in Nigerian patients with benign essential hypertension. PMID- 25126875 TI - Implant failure in lower limb long bone diaphyseal fractures at a tertiary hospital in Ile- Ife. Nigeria. AB - AIMS AND OBJECTIVES: This included determining aetiology of failure and comparing the failure rate in implant fixations using solid intramedullary nail and DCP. PATIENTS AND METHODS: A retrospective study conducted at the Orthopaedic Department, Obafemi Awolowo University Teaching Hospital, Ile-Ife,Nigeria. Records of all operated cases of lower limb long bone diaphyseal fractures including those with failed fixations from August 2006-July 2011 were reviewed. Data retrieved included type of implant used, aetiology and characteristics of Implant failure. Data were analysed using SPSS version 16. Frequency distribution of the variables of interest was done. Difference in failure rate of intramedullary nail versus DCP was tested using chi-square. Statistical significance was inferred at p<0.05. RESULTS: A total of 280 patients were studied out of which two hundred and twenty-one patients had long bone diaphyseal fractures and met inclusion criteria, of which 135 had intramedullary nail fixation and 86 had DCP. The rate of implant failure in intramedullary nail was 1.5% while it was 5.8% in patients with DCP (p=0.113; 0R=4.10; 95% CI=0.65- 43.77). Implant fracture was the commonest type of failure seen (100% versus 60%) and non union was the commonest cause of failure seen (50% versus 40%) in the intramedullary nailing and DCP groups respectively. CONCLUSION: The likelihood of a failed implant is higher in fixations done with DCP compared with intramedullary nail though the difference was not statistically significant. Commonest reason for failure in both groups was non-union. Findings from this study may guide surgeons in choice of implant in the management of long bone fractures. PMID- 25126876 TI - Polymorphisms in SPARC and coal workers' pneumoconiosis risk in a Chinese population. AB - BACKGROUND: The SPARC is a crucial matricellular protein and may influence the course of various diseases like tumor metastasis and fibrosis. In the present study, we investigated the association between the potential functional polymorphisms in SPARC and coal workers' pneumoconiosis (CWP) risk in a Chinese population. METHODS: Five potentially functional polymorphisms (rs1059279, rs1059829, rs1053411, rs2304052 and rs4958281) in SPARC were genotyped and analyzed in a case-control study including 697 CWP cases and 694 controls. The genotyping was used by the TaqMan method with the ABI 7900HT Real Time PCR system. RESULTS: Our results revealed that three SNPs (rs1059279, rs1059829, rs1053411) were significantly associated with increased risk of CWP under an additive model (OR = 1.35, 95%CI = 1.06-1.71, P = 0.015 for rs1059279; OR = 1.20, 95%CI = 1.03-1.39, P = 0.021 for rs1059829; OR = 1.31, 95%CI = 1.03-1.65, P = 0.025 for rs1053411). In the stratification analysis, significant associations were observed between each of these three SNPs and patients with 0-20 pack-years of smoking (OR = 1.73, 95%CI = 1.21-2.45 for rs1059279; OR = 1.48, 95%CI = 1.07 2.05 for rs105982; OR = 1.58, 95%CI = 1.13-2.22 for rs1053411). Furthermore, the association between rs1059279 and CWP risk remained significant among subjects with over 27 years of exposure (OR = 1.27, 95%CI = 1.03-1.56, P = 0.023). In the combined analysis of these five polymorphisms, individuals with multiple risk alleles had a higher risk of CWP (Ptrend = 0.015). CONCLUSION: Our results indicate that three functional SPARC SNPs are associated with an increased risk of CWP in a Chinese population. Further functional research and validation studies with diverse populations are warranted to confirm our findings. PMID- 25126878 TI - ICU physician-based determinants of life-sustaining therapy during nights and weekends: French multicenter study from the Outcomerea Research Group. AB - OBJECTIVE: Patient- and organization-related factors are the most common influences affecting the ICU decision-making process. Few studies have investigated ICU physician-related factors and life-sustaining treatment use during nights and weekends, when staffing ratios are low. Here, we described patients admitted during nights/weekends and looked for physician-related determinants of life-sustaining treatment use in these patients after adjustment for patient- and center-related factors. DESIGN: Multicenter observational cohort study of admission procedures during nights/weekends shifts. SUBJECTS: ICU physicians working nights/weekends in 6 French ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and intensity of care were extracted from the prospective Outcomerea database. Physician characteristics were age, gender, religion and religiosity, ICU experience, specialty, being a permanent ICU staff member, degree in ethics, and degree in intensive care. We used hierarchical mixed models to adjust on center, physician random effects, and admission patient characteristics. Of 156 physicians contacted, 119 (77%) participated. Patients admitted during nights/weekends were younger and had fewer comorbidities and lower treatment intensity during the shift. ICU physicians who are younger than 35 years used more renal replacement therapy (odds ratio, 1.04; 95% CI, 1-1.07; p = 0.04), invasive mechanical ventilation (odds ratio, 1.09; 95% CI, 1.1-1.19; p = 0.04), and vasopressors (odds ratio, 1.16; 95% CI, 1.09-1.23; p < 0.0001). Internal or emergency medicine as the primary specialty was associated with invasive mechanical ventilation (odds ratio, 1.14; 95% CI, 1.04-1.24; p = 0.004) and vasopressor use (odds ratio, 1.09; 95% CI, 1.02-1.17; p = 0.01). Noninvasive ventilation was used less often by physicians with more than 10 years of night/weekend shifts and more often by those with religious beliefs (odds ratio, 1.05; 95% CI, 1.01-1.08; p = 0.008). CONCLUSIONS: Patients admitted during nights/weekends were younger and had fewer comorbidities. Age, specialty, ICU experience, and religious beliefs of the physicians were significantly associated life-sustaining treatments used. PMID- 25126877 TI - Deficiency of the two-pore-domain potassium channel TREK-1 promotes hyperoxia induced lung injury. AB - OBJECTIVES: We previously reported the expression of the two-pore-domain K channel TREK-1 in lung epithelial cells and proposed a role for this channel in the regulation of alveolar epithelial cytokine secretion. In this study, we focused on investigating the role of TREK-1 in vivo in the development of hyperoxia-induced lung injury. DESIGN: Laboratory animal experiments. SETTING: University research laboratory. SUBJECTS: Wild-type and TREK-1-deficient mice. INTERVENTIONS: Mice were anesthetized and exposed to 1) room air, no mechanical ventilation, 2) 95% hyperoxia for 24 hours, and 3) 95% hyperoxia for 24 hours followed by mechanical ventilation for 4 hours. MEASUREMENTS AND MAIN RESULTS: Hyperoxia exposure accentuated lung injury in TREK-1-deficient mice but not controls, resulting in increase in lung injury scores, bronchoalveolar lavage fluid cell numbers, and cellular apoptosis and a decrease in quasi-static lung compliance. Exposure to a combination of hyperoxia and injurious mechanical ventilation resulted in further morphological lung damage and increased lung injury scores and bronchoalveolar lavage fluid cell numbers in control but not TREK-1-deficient mice. At baseline and after hyperoxia exposure, bronchoalveolar lavage cytokine levels were unchanged in TREK-1-deficient mice compared with controls. Exposure to hyperoxia and mechanical ventilation resulted in an increase in bronchoalveolar lavage interleukin-6, monocyte chemotactic protein-1, and tumor necrosis factor-alpha levels in both mouse types, but the increase in interleukin-6 and monocyte chemotactic protein-1 levels was less prominent in TREK-1-deficient mice than in controls. Lung tissue macrophage inflammatory protein-2, keratinocyte-derived cytokine, and interleukin-1beta gene expression was not altered by hyperoxia in TREK-1-deficient mice compared with controls. Furthermore, we show for the first time TREK-1 expression on alveolar macrophages and unimpaired tumor necrosis factor-alpha secretion from TREK-1-deficient macrophages. CONCLUSIONS: TREK-1 deficiency resulted in increased sensitivity of lungs to hyperoxia, but this effect is less prominent if overwhelming injury is induced by the combination of hyperoxia and injurious mechanical ventilation. TREK-1 may constitute a new potential target for the development of novel treatment strategies against hyperoxia-induced lung injury. PMID- 25126879 TI - Early prediction of persistent organ failure by soluble CD73 in patients with acute pancreatitis*. AB - OBJECTIVE: New biomarkers are needed to better predict the severity of acute pancreatitis. CD73/ecto-5'-nucleotidase is an enzyme that generates adenosine, which dampens inflammation and improves vascular barrier function in several disease models. CD73 also circulates in a soluble form in the blood. We studied whether levels of soluble form of CD73 predict the development of organ failure in acute pancreatitis. DESIGN: A prospective cohort study of patients with acute pancreatitis from 2003 to 2007. SETTING: Admissions to the biggest tertiary care hospital in Finland. PATIENTS: One hundred sixty-one patients with acute pancreatitis, of which 107 were subclassified according to the revised Atlanta criteria into mild, 29 into moderately severe and 25 into severe. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum and blood cell samples were collected at admission. Protein levels of soluble form of CD73 in serum were determined using a novel enzyme-linked immunosorbent assay, activity of soluble form of CD73 using radioactive enzyme assays, and CD73 messenger RNA levels from leukocytes using quantitative polymerase chain reaction. Activity and protein concentration of soluble form of CD73, and messenger RNA level of CD73 all decreased along with the disease severity (p <= 0.01 for all). The activity of soluble form of CD73 at admission predicted the development of the severe pancreatitis in different groups of the patients. The area under the receiver-operating characteristic curve value for activity of soluble form of CD73 was 0.65 (95% CI, 0.51-0.80) among a subgroup of patients comprising moderately severe and severe disease, 0.79 (95% CI, 0.69-0.88) among all patients including mild pancreatitis, and 0.75 (95% CI, 0.60-0.89) among patients who had no signs of organ failure (modified Marshall score < 2) at admission. Especially, in the last-mentioned group, activity of soluble form of CD73 was better than C-reactive protein or creatinine in predicting the severe pancreat CONCLUSIONS: : Activity of soluble form of CD73 at admission to hospital has prognostic value in predicting the development of the severe form of acute pancreatitis. PMID- 25126881 TI - Environmentally benign process for the preparation of antimicrobial alpha methylene-beta-hydroxy-gamma-butyrolactone (tulipalin B) from tulip biomass. AB - Tulipalin B (alpha-methylene-beta-hydroxy-gamma-butyrolactone, PaB) is an antimicrobial natural product occurring in tulip (Tulipa gesneriana). PaB is directly formed from the precursor glucose ester 6-tuliposide B (PosB) by endogenous Pos-converting enzyme (TCE). Despite the potential usefulness of antibacterial PaB in various industrial applications, lack of facile synthetic schemes hampers its practical use. Herein, we describe an environmentally benign and facile process for the preparation of PaB using tulip biomass materials based on one-step enzyme reaction catalyzed by TCE without the use of petroleum-derived solvents. By screening 115 tulip cultivars, we found three elite cultivars, which accumulated PosB almost exclusively in flower tissues. The flower extracts with aqueous ethanol were partially purified with activated charcoal and subjected to the enzyme reaction with reusable immobilized TCE prepared from bulb crude extracts. The reaction was completed in a few hours at room temperature, and PaB was purified with activated charcoal and ethanol in a batch-wise manner. PMID- 25126883 TI - College Health's response to "not alone". PMID- 25126880 TI - International study on microcirculatory shock occurrence in acutely ill patients. AB - OBJECTIVES: Microcirculatory alterations are associated with adverse outcome in subsets of critically ill patients. The prevalence and significance of microcirculatory alterations in the general ICU population are unknown. We studied the prevalence of microcirculatory alterations in a heterogeneous ICU population and its predictive value in an integrative model of macro- and microcirculatory variables. DESIGN: Multicenter observational point prevalence study. SETTING: The Microcirculatory Shock Occurrence in Acutely ill Patients study was conducted in 36 ICUs worldwide. PATIENTS: A heterogeneous ICU population consisting of 501 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, hemodynamic, and laboratory data were collected in all ICU patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging was performed to determine the prevalence of an abnormal capillary microvascular flow index (< 2.6) and its additional value in predicting hospital mortality. In 501 patients with a median Acute Physiology and Chronic Health Evaluation II score of 15 (10-21), a Sequential Organ Failure Assessment score of 5 (2-8), and a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI, 1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963 0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p = 0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28 3.62; p = 0.004) were independent risk factors for hospital mortality, but not abnormal microvascular flow index. In reference to microvascular flow index, a significant interaction was observed with tachycardia. In patients with tachycardia, the presence of an abnormal microvascular flow index was an independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95% CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for the total group of patients. CONCLUSIONS: In a heterogeneous ICU population, an abnormal microvascular flow index was present in 17% of patients. This was not associated with mortality. However, in patients with tachycardia, an abnormal microvascular flow index was independently associated with an increased risk of hospital death. PMID- 25126882 TI - The impact of nitration on the structure and immunogenicity of the major birch pollen allergen Bet v 1.0101. AB - Allergy prevalence has increased in industrialized countries. One contributing factor could be pollution, which can cause nitration of allergens exogenously (in the air) or endogenously (in inflamed lung tissue). We investigated the impact of nitration on both the structural and immunological behavior of the major birch pollen allergen Bet v 1.0101 to determine whether nitration might be a factor in the increased incidence of allergy. Bet v 1.0101 was nitrated with tetranitromethane. Immune effects were assessed by measuring the proliferation of specific T-cell lines (TCLs) upon stimulation with different concentrations of nitrated and unmodified allergen, and by measurement of cytokine release of monocyte-derived dendritic cells (moDCs) and primary DCs (primDCs) stimulated with nitrated versus unmodified allergen. HPLC-MS, crystallography, gel electrophoresis, amino acid analysis, size exclusion chromatography and molecular dynamics simulation were performed to characterize structural changes after nitration of the allergen. The proliferation of specific TCLs was higher upon stimulation with the nitrated allergen in comparison to the unmodified allergen. An important structural consequence of nitration was oligomerization. Moreover, analysis of the crystal structure of nitrated Bet v 1.0101 showed that amino acid residue Y83, located in the hydrophobic cavity, was nitrated to 100%. Both moDCs and primDCs showed decreased production of TH1-priming cytokines, thus favoring a TH2 response. These results implicate that nitration of Bet v 1.0101 might be a contributing factor to the observed increase in birch pollen allergy, and emphasize the importance of protein modifications in understanding the molecular basis of allergenicity. PMID- 25126884 TI - Evelyn Wiener. PMID- 25126885 TI - Comparison of skin and soft tissue infections caused by Vibrio and Aeromonas species. AB - BACKGROUND: The aim of this study was to compare skin and soft tissue infections (SSTIs) caused by Vibrio and Aeromonas spp. METHODS: Patients whose cultures yielded Vibrio or Aeromonas spp. from July 2004 to June 2010 were retrieved from the computerized database of the bacteriology laboratory at a hospital in southern Taiwan. The medical records were reviewed for all patients fulfilling the criteria of monomicrobial Vibrio or Aeromonas spp. SSTIs and the clinical characteristics were analyzed. RESULTS: During the study period, there were 28 patients with Vibrio spp. and 26 patients with Aeromonas spp., respectively. Vibrio vulnificus (n=25) and A. hydrophila (n=14) were the most common spp. There were no significant differences in age, gender, underlying diseases between patients with Vibrio and Aeromonas SSTIs. In comparison to Aeromonas SSTIs, more patients with Vibrio SSTIs were complicated with acute respiratory failure (39.3% vs. 3.8%, p=0.002) and required intensive care unit admission (50.0% vs. 7.7%, p<0.001). Furthermore, patients with Aeromonas SSTIs had a higher likelihood of discharge alone within 30 days than Vibrio SSTIs (p=0.049). The difference in in hospital mortality among the two groups was not statistically significant (p=0.11). CONCLUSION: Both Aeromonas and Vibrio spp. cause SSTIs in southern Taiwan and the pathogenicity of Vibrio spp. might be higher than Aeromonas spp. PMID- 25126886 TI - Production and partial purification of tannase from Aspergillus ficuum Gim 3.6. AB - A novel fungal strain, Aspergillus ficuum Gim 3.6, was evaluated for its tannase producing capability in a wheat bran-based solid-state fermentation. Thin-layer chromatography (TLC) analysis revealed that the strain was able to degrade tannic acid to gallic acid and pyrogallol during the fermentation process. Quantitation of enzyme activity demonstrated that this strain was capable of producing a relatively high yield of extracellular tannase. Single-factor optimization of process parameters resulted in high yield of tannase after 60 hr of incubation at a pH of 5.0 at 30 degrees C, 1 mL of inoculum size, and 1:1 solid-liquid ratio in the presence of 2.0% (w/v) tannic acid as inducer. The potential of aqueous two phase extraction (ATPE) for the purification of tannase was investigated. Influence of various parameters such as phase-forming salt, molecular weight of polyethylene glycol (PEG), pH, and stability ratio on tannase partition and purification was studied. In all the systems, the target enzyme was observed to preferentially partition to the PEG-rich top phase, and the best result of purification (2.74-fold) with an enzyme activity recovery of 77.17% was obtained in the system containing 17% (w/w) sodium citrate and 18.18% (w/w) PEG1000, at pH 7.0. PMID- 25126887 TI - Growth kinetics and growth mechanism of ultrahigh mass density carbon nanotube forests on conductive Ti/Cu supports. AB - We evaluate the growth kinetics and growth mechanism of ultrahigh mass density carbon nanotube forests. They are synthesized by chemical vapor deposition at 450 degrees C using a conductive Ti/Cu support and Co-Mo catalyst system. We find that Mo stabilizes Co particles preventing lift off during the initial growth stage, thus promoting the growth of ultrahigh mass density nanotube forests by the base growth mechanism. The morphology of the forest gradually changes with growth time, mostly because of a structural change of the catalyst particles. After 100 min growth, toward the bottom of the forest, the area density decreases from ~ 3-6 * 10(11) cm(-2) to ~ 5 * 10(10) cm(-2) and the mass density decreases from 1.6 to 0.38 g cm(-3). We also observe part of catalyst particles detached and embedded within nanotubes. The progressive detachment of catalyst particles results in the depletion of the catalyst metals on the substrate surfaces. This is one of the crucial reasons for growth termination and may apply to other catalyst systems where the same features are observed. Using the packed forest morphology, we demonstrate patterned forest growth with a pitch of ~ 300 nm and a line width of ~ 150 nm. This is one of the smallest patterning of the carbon nanotube forests to date. PMID- 25126888 TI - Effects of a brief school-based media literacy intervention on digital media use in adolescents: cluster randomized controlled trial. AB - The aim of this study was to evaluate the effects of a four-session school-based media literacy curriculum on adolescent computer gaming and Internet use behavior. The study comprised a cluster randomized controlled trial with three assessments (baseline, posttest, and 12-month follow-up). At baseline, a total of 2,303 sixth and seventh grade adolescents from 27 secondary schools were assessed. Of these, 1,843 (80%) could be reached at all three assessments (Mage=12.0 years; SD=0.83). Students of the intervention group received the media literacy program Vernetzte www.Welten ("Connected www.Worlds ") implemented by trained teachers during class time. The control group attended regular class. Main outcome measures were adolescents' computer gaming and Internet use: days per month, hours per day, and addictive use patterns. Parental media monitoring and rules at home were assessed as secondary outcomes. Results of multilevel growth-curve models revealed a significant intervention effect in terms of a lower increase in self-reported gaming frequency (beta = -1.10 [95% CI -2.06, 0.13]), gaming time (beta = -0.27 [95% CI -0.40, -0.14]), and proportion of excessive gamers (AOR=0.21 [95% CI 0.08, 0.57]) in the intervention group. There were also significant group-time interactions for the addictive gaming scale (beta=-0.08 [95% CI -0.12, -0.04]), and the Internet Addiction Scale (beta = 0.06 [95% CI -0.10, -0.01]). No effect was found for days and hours of Internet use or parental media behavior. The study shows that the program Vernetzte www.Welten can influence adolescents' media use behavior. Future research should address mediating and moderating variables of program effects. PMID- 25126889 TI - Synthesis, biological evaluation, and molecular modeling of new 3 (cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) Oxime (GEBR-7b) related phosphodiesterase 4D (PDE4D) inhibitors. AB - A new series of 3-(cyclopentyloxy)-4-methoxyphenyl derivatives, structurally related to our hit GEBR-4a (1) and GEBR-7b (2), has been designed by changing length and functionality of the chain linking the catecholic moiety to the terminal cycloamine portion. Among the numerous molecules synthesized, compounds 8, 10a, and 10b showed increased potency as PDE4D enzyme inhibitors with respect to 2 and a good selectivity against PDE4A4, PDE4B2, and PDE4C2 enzymes, without both cytotoxic and genotoxic effects. The ability to enhance cAMP level in neuronal cells was assessed for compound 8. SAR considerations, also confirmed by in silico docking simulations, evidenced that both chain and amino terminal function characterized by higher hydrophilicity are required for a good and selective inhibitor-catalytic pocket interaction. PMID- 25126890 TI - IWBDA 2013. PMID- 25126893 TI - PR-PR: cross-platform laboratory automation system. AB - To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Golden Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms. PMID- 25126894 TI - Chiral gold nanowires with Boerdijk-Coxeter-Bernal structure. AB - A Boerdijk-Coxeter-Bernal (BCB) helix is made of linearly stacked regular tetrahedra (tetrahelix). As such, it is chiral without nontrivial translational or rotational symmetries. We demonstrate here an example of the chiral BCB structure made of totally symmetrical gold atoms, created in nanowires by direct chemical synthesis. Detailed study by high-resolution electron microscopy illustrates their elegant chiral structure and the unique one-dimensional "pseudo periodicity". The BCB-type atomic packing mode is proposed to be a result of the competition and compromise between the lattice and surface energy. PMID- 25126895 TI - Identification and mitigation of a reactive metabolite liability associated with aminoimidazoles. AB - Reactive metabolites (RMs) have been implicated as causal factors in many drug associated idiosyncratic toxicities. This study aims at identification and mitigation of an RM liability associated with aminoimidazole and amino(aza)benzimidazole structural motifs from an antimalarial project. Nineteen compounds with different structural modifications were studied in rat and human liver microsomes using glutathione (GSH) and N-acetyl cysteine (NAC) as trapping agents for RM. Metabolite profiling of aminoimidazole compounds in initial studies revealed the presence of dihydrodiol metabolites suggestive of reactive epoxide precursors, confirmed by the identification of a dihydrohydroxy GSH conjugate in GSH supplemented incubations. Substitution of methyl group at a potential site of metabolism blocked the epoxidation; however, formation of an imine-methide RM was suspected. Masking the site of metabolism via benzimidazole and 4/7-azabenzimidazole resulted in the possible formation of quinone-imine intermediates as a product of bioactivation. Further, substitutions with electron withdrawing groups and steric crowding did not address this liability. Mitigation of bioactivation was achieved with 5/6-azabenzimidazole and with CF3 substitution at the 6-position of the 7-azabenzimidazole ring. Moreover, compounds devoid of imidazole -NH2 do not undergo bioactivation. This study, therefore, establishes aminoimidazole and amino(aza)benzimidazoles as potential toxicophores and describes ways to mitigate this bioactivation liability by chemical modification. PMID- 25126897 TI - Size-resolved deposition rates for ultrafine and submicrometer particles in a residential housing unit. AB - We estimated the size-resolved particle deposition rates for the ultrafine and submicrometer particles using a nonlinear regression method with unknown particle background concentrations during nonsourced period following a controlled sourced period in a well-mixed residential environment. A dynamic adjustment method in conjunction with the constant injection of tracer gas was used to maintain the air exchange rate at three target levels across the range of 0.61-1.24 air change per hour (ACH). Particle deposition was found to be highly size dependent with rates ranging from 0.68 +/- 0.10 to 5.03 +/- 0.20 h(-1) (mean +/- s.e.). Our findings also suggest that the effect of air exchange on the particle deposition under enhanced air mixing was relatively small when compared to both the strong influence of size-dependent deposition mechanisms and the effects of mechanical air mixing by fans. Nonetheless, the significant association between air exchange and particle deposition rates for a few size categories indicated potential influence of air exchange on particle deposition. In the future, the proposed approach can be used to explore the separate or composite effects between air exchange and air mixing on particle deposition rates, which will contribute to improved assessment of human exposure to ultrafine and submicrometer particles. PMID- 25126896 TI - Labeled EF-Tus for rapid kinetic studies of pretranslocation complex formation. AB - The universally conserved translation elongation factor EF-Tu delivers aminoacyl(aa)-tRNA in the form of an aa-tRNA.EF-Tu.GTP ternary complex (TC) to the ribosome where it binds to the cognate mRNA codon within the ribosomal A site, leading to formation of a pretranslocation (PRE) complex. Here we describe preparation of QSY9 and Cy5 derivatives of the variant E348C-EF-Tu that are functional in translation elongation. Together with fluorophore derivatives of aa tRNA and of ribosomal protein L11, located within the GTPase associated center (GAC), these labeled EF-Tus allow development of two new FRET assays that permit the dynamics of distance changes between EF-Tu and both L11 (Tu-L11 assay) and aa tRNA (Tu-tRNA assay) to be determined during the decoding process. We use these assays to examine: (i) the relative rates of EF-Tu movement away from the GAC and from aa-tRNA during decoding, (ii) the effects of the misreading-inducing antibiotics streptomycin and paromomycin on tRNA selection at the A-site, and (iii) how strengthening the binding of aa-tRNA to EF-Tu affects the rate of EF-Tu movement away from L11 on the ribosome. These FRET assays have the potential to be adapted for high throughput screening of ribosomal antibiotics. PMID- 25126898 TI - Large negatively charged organic host molecules as inhibitors of endonuclease enzymes. AB - Three large negatively charged organic host molecules; beta-cyclodextrin sulphate, para-sulphonato-calix[6]arene and para-sulphonato-calix[8]arene have been shown to be effective inhibitors of endonuclease in the low micromolar range, additionally para-sulphonato-calix[8]arene is a partial inhibitor of rhDNase I. PMID- 25126899 TI - Colorectal cancer detection using targeted serum metabolic profiling. AB - Colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the world. Despite an expanding knowledge of its molecular pathogenesis during the past two decades, robust biomarkers to enable screening, surveillance, and therapy monitoring of CRC are still lacking. In this study, we present a targeted liquid chromatography-tandem mass spectrometry-based metabolic profiling approach for identifying biomarker candidates that could enable highly sensitive and specific CRC detection using human serum samples. In this targeted approach, 158 metabolites from 25 metabolic pathways of potential significance were monitored in 234 serum samples from three groups of patients (66 CRC patients, 76 polyp patients, and 92 healthy controls). Partial least-squares-discriminant analysis (PLS-DA) models were established, which proved to be powerful for distinguishing CRC patients from both healthy controls and polyp patients. Receiver operating characteristic curves generated based on these PLS-DA models showed high sensitivities (0.96 and 0.89, respectively, for differentiating CRC patients from healthy controls or polyp patients), good specificities (0.80 and 0.88), and excellent areas under the curve (0.93 and 0.95). Monte Carlo cross validation was also applied, demonstrating the robust diagnostic power of this metabolic profiling approach. PMID- 25126900 TI - Salt effects on lamellar repeat distance depending on head groups of neutrally charged lipids. AB - Change in lamellar repeat distances of neutrally charged lipids upon addition of monovalent salts was measured with small-angle X-ray scattering for combinations of two lipids (PC and PE lipids) and six salts. Large dependence on lipid head group is observed in addition to those on added cation and anion. The ion and lipid dependences have little correlation with measured surface potentials of lipid membranes. These results indicate that the lamellar swelling by salt is not explained through balance among interactions considered previously (van der Waals interaction, electrostatic repulsion emerged by ion binding, etc.). It is suggested that effect of water structure, which is affected by not only ions but also lipid itself, should be taken into account for understanding membrane membrane interactions, as in the Hofmeister effect. PMID- 25126901 TI - Temporal quantum correlations and Leggett-Garg inequalities in multilevel systems. AB - We show that the quantum bound for temporal correlations in a Leggett-Garg test, analogous to the Tsirelson bound for spatial correlations in a Bell test, strongly depends on the number of levels N that can be accessed by the measurement apparatus via projective measurements. We provide exact bounds for small N that exceed the known bound for the Leggett-Garg inequality, and we show that in the limit N->infinity the Leggett-Garg inequality can be violated up to its algebraic maximum. PMID- 25126902 TI - Measuring a topological transition in an artificial spin-1/2 system. AB - We present measurements of a topological property, the Chern number (C_{1}), of a closed manifold in the space of two-level system Hamiltonians, where the two level system is formed from a superconducting qubit. We manipulate the parameters of the Hamiltonian of the superconducting qubit along paths in the manifold and extract C_{1} from the nonadiabatic response of the qubit. By adjusting the manifold such that a degeneracy in the Hamiltonian passes from inside to outside the manifold, we observe a topological transition C_{1}=1->0. Our measurement of C_{1} is quantized to within 2% on either side of the transition. PMID- 25126903 TI - Invariants of broken discrete symmetries. AB - The parity and Bloch theorems are generalized to the case of broken global symmetry. Local inversion or translation symmetries in one dimension are shown to yield invariant currents that characterize wave propagation. These currents map the wave function from an arbitrary spatial domain to any symmetry-related domain. Our approach addresses any combination of local symmetries, thus applying, in particular, to acoustic, optical, and matter waves. Nonvanishing values of the invariant currents provide a systematic pathway to the breaking of discrete global symmetries. PMID- 25126904 TI - Steering bound entangled States: a counterexample to the stronger Peres conjecture. AB - Quantum correlations are at the heart of many applications in quantum information science and, at the same time, they form the basis for discussions about genuine quantum effects and their difference to classical physics. On one hand, entanglement theory provides the tools to quantify correlations in information processing and many results have been obtained to discriminate useful entanglement, which can be distilled to a pure form, from bound entanglement, being of limited use in many applications. On the other hand, for discriminating quantum phenomena from their classical counterparts, Schrodinger and Bell introduced the notions of steering and local hidden variable models. We provide a method to generate systematically bound entangled quantum states which can still be used for steering and, therefore, to rule out local hidden state models. This sheds light on the relations between the various views on quantum correlations and disproves a widespread conjecture known as the stronger Peres conjecture. For practical applications, it implies that even the weakest form of entanglement can be certified in a semidevice independent way. PMID- 25126905 TI - Many-body interactions with tunable-coupling transmon qubits. AB - The efficient implementation of many-body interactions in superconducting circuits allows for the realization of multipartite entanglement and topological codes, as well as the efficient simulation of highly correlated fermionic systems. We propose the engineering of fast multiqubit interactions with tunable transmon-resonator couplings. This dynamics is obtained by the modulation of magnetic fluxes threading superconducting quantum interference device loops embedded in the transmon devices. We consider the feasibility of the proposed implementation in a realistic scenario and discuss potential applications. PMID- 25126906 TI - Nonequilibrium dynamics of one-dimensional hard-core anyons following a quench: complete relaxation of one-body observables. AB - We demonstrate the role of interactions in driving the relaxation of an isolated integrable quantum system following a sudden quench. We consider a family of integrable hard-core lattice anyon models that continuously interpolates between noninteracting spinless fermions and strongly interacting hard-core bosons. A generalized Jordan-Wigner transformation maps the entire family to noninteracting fermions. We find that, aside from the singular free-fermion limit, the entire single-particle density matrix and, therefore, all one-body observables relax to the predictions of the generalized Gibbs ensemble (GGE). This demonstrates that, in the presence of interactions, correlations between particles in the many-body wave function provide the effective dissipation required to drive the relaxation of all one-body observables to the GGE. This relaxation does not depend on translational invariance or the tracing out of any spatial domain of the system. PMID- 25126907 TI - Naturalness and the weak gravity conjecture. AB - The weak gravity conjecture (WGC) is an ultraviolet consistency condition asserting that an Abelian force requires a state of charge q and mass m with q>m/m_{Pl}. We generalize the WGC to product gauge groups and study its tension with the naturalness principle for a charged scalar coupled to gravity. Reconciling naturalness with the WGC either requires a Higgs phase or a low cutoff at Lambda~qm_{Pl}. If neither applies, one can construct simple models that forbid a natural electroweak scale and whose observation would rule out the naturalness principle. PMID- 25126908 TI - Relative entropies in conformal field theory. AB - Relative entropy is a measure of distinguishability for quantum states, and it plays a central role in quantum information theory. The family of Renyi entropies generalizes to Renyi relative entropies that include, as special cases, most entropy measures used in quantum information theory. We construct a Euclidean path-integral approach to Renyi relative entropies in conformal field theory, then compute the fidelity and the relative entropy of states in one spatial dimension at zero and finite temperature using a replica trick. In contrast to the entanglement entropy, the relative entropy is free of ultraviolet divergences, and is obtained as a limit of certain correlation functions. The relative entropy of two states provides an upper bound on their trace distance. PMID- 25126909 TI - Radiative electroweak symmetry breaking model perturbative all the way to the Planck scale. AB - We discuss an extension of the standard model by fields not charged under standard model gauge symmetry in which the electroweak symmetry breaking is driven by the Higgs quartic coupling itself without the need for a negative mass term in the potential. This is achieved by a scalar field S with a large coupling to the Higgs field at the electroweak scale which is driven to very small values at high energies by the gauge coupling of a hidden symmetry under which S is charged. This model can remain perturbative all the way to the Planck scale. The Higgs boson is fully standard-model-like in its couplings to fermions and gauge bosons. However, the effective cubic and quartic self-couplings of the Higgs boson are significantly enhanced. PMID- 25126910 TI - Freeze-out parameters from electric charge and baryon number fluctuations: is there consistency? AB - Recent results for moments of multiplicity distributions of net protons and net electric charge from the STAR Collaboration are compared to lattice QCD results for higher order fluctuations of baryon number and electric charge by the Wuppertal-Budapest Collaboration, with the purpose of extracting the freeze-out temperature and chemical potential. All lattice simulations are performed for a system of 2+1 dynamical quark flavors, at the physical mass for light and strange quarks; all results are continuum extrapolated. We show that it is possible to extract an upper value for the freeze-out temperature, as well as precise baryochemical potential values corresponding to the four highest collision energies of the experimental beam energy scan. Consistency between the freeze-out parameters obtained from baryon number and electric charge fluctuations is found. The freeze-out chemical potentials are now in agreement with the statistical hadronization model. PMID- 25126912 TI - Neutron pair transfer in (60)Ni+(116)Sn far below the Coulomb barrier. AB - An excitation function of one- and two-neutron transfer channels for the ^{60}Ni+^{116}Sn system has been measured with the magnetic spectrometer PRISMA in a wide energy range, from the Coulomb barrier to far below it. The experimental transfer probabilities are well reproduced, for the first time with heavy ions, in absolute values and in slope by microscopic calculations which incorporate nucleon-nucleon pairing correlations. PMID- 25126913 TI - Proton-neutron pairing correlations in the self-conjugate nucleus (38)K probed via a direct measurement of the isomer shift. AB - A marked difference in the nuclear charge radius was observed between the I^{pi}=3^{+} ground state and the I^{pi}=0^{+} isomer of ^{38}K and is qualitatively explained using an intuitive picture of proton-neutron pairing. In a high-precision measurement of the isomer shift using bunched-beam collinear laser spectroscopy at CERN-ISOLDE, a change in the mean-square charge radius of ?r_{c}^{2}?(^{38}K^{m})-?r_{c}^{2}?(^{38}K^{g})=0.100(6) fm^{2} was obtained. This is an order of magnitude more accurate than the result of a previous indirect measurement from which it was concluded that both long-lived states in ^{38}K have similar charge radii. Our observation leads to a substantially different understanding since the difference in charge radius is, moreover, opposite in sign to previously reported theoretical predictions. It is demonstrated that the observed isomer shift can be reproduced by large-scale shell-model calculations including proton and neutron excitations across the N,Z=20 shell gaps, confirming the significance of cross-shell correlations in the region of ^{40}Ca. PMID- 25126914 TI - Entanglement generation using discrete solitons in Coulomb crystals. AB - Laser-cooled and trapped ions can crystallize and feature discrete solitons that are nonlinear, topologically protected configurations of the Coulomb crystal. Such solitons, as their continuum counterparts, can move within the crystal, while their discreteness leads to the existence of a gap-separated, spatially localized motional mode of oscillation above the spectrum. Suggesting that these unique properties of discrete solitons can be used for generating entanglement between different sites of the crystal, we study a detailed proposal in the context of state-of-the-art experimental techniques. We analyze the interaction of periodically driven planar ion crystals with optical forces, revealing the effects of micromotion in radio-frequency traps inherent to such structures, as opposed to linear ion chains. The proposed method requires Doppler cooling of the crystal and sideband cooling of the soliton's localized modes alone. Since the gap separation of the latter is nearly independent of the crystal size, this approach could be particularly useful for producing entanglement and studying system-environment interactions in large, two- and possibly three-dimensional systems. PMID- 25126915 TI - Deexcitation dynamics of superhydrogenated polycyclic aromatic hydrocarbon cations after soft-x-ray absorption. AB - We have investigated the response of superhydrogenated gas-phase coronene cations upon soft x-ray absorption. Carbon (1s)?pi^{?} transitions were resonantly excited at hnu=285 eV. The resulting core hole is then filled in an Auger decay process, with the excess energy being released in the form of an Auger electron. Predominantly highly excited dications are thus formed, which cool down by hydrogen emission. In superhydrogenated systems, the additional H atoms act as a buffer, quenching loss of native H atoms and molecular fragmentation. Dissociation and transition state energies for several H loss channels were computed by means of density functional theory. Using these energies as input into an Arrhenius-type cascade model, very good agreement with the experimental data is found. The results have important implications for the survival of polyaromatic hydrocarbons in the interstellar medium and reflect key aspects of graphene hydrogenation. PMID- 25126917 TI - Three-body recombination at vanishing scattering lengths in an ultracold bose gas. AB - We report on measurements of three-body recombination loss rates in an ultracold gas of ^{7}Li atoms in the extremely nonuniversal regime where the two-body scattering length vanishes. We show that the loss rate coefficient is well defined and can be described by two-body parameters only: the scattering length a and the effective range R_{e}. We find the rate to be energy independent, and, by connecting our results with previously reported measurements in the universal limit, we cover the behavior of the three-body recombination rate in the whole range from weak to strong two-body interactions. We identify a nontrivial magnetic field value in the nonuniversal regime where the rate should be suppressed. PMID- 25126916 TI - Eley-rideal reactions with N atoms at Ru(0001): formation of NO and N(2). AB - Forward-directed NO molecules with large translational energies are formed upon exposure of an O-covered Ru(0001) surface to a nitrogen (N+N_{2}) beam. This is an unequivocal experimental demonstration of the Eley-Rideal reaction for a "heavy" (i.e., nonhydrogenated) neutral system. The time dependence of prompt NO formation exhibits an exceptionally fast decay as a consequence of shifting reaction pathways and probabilities over the course of the exposure. Prompt production shuts down as the O coverage decreases due to competition from more favorable Eley-Rideal production of N_{2}. PMID- 25126918 TI - Single-photon transistor mediated by interstate Rydberg interactions. AB - We report on the realization of an all-optical transistor by mapping gate and source photons into strongly interacting Rydberg excitations with different principal quantum numbers in an ultracold atomic ensemble. We obtain a record switch contrast of 40% for a coherent gate input with mean photon number one and demonstrate attenuation of source transmission by over ten photons with a single gate photon. We use our optical transistor to demonstrate the nondestructive detection of a single Rydberg atom with a fidelity of 0.72(4). PMID- 25126919 TI - Single-photon transistor using a Forster resonance. AB - An all-optical transistor is a device in which a gate light pulse switches the transmission of a target light pulse with a gain above unity. The gain quantifies the change of the transmitted target photon number per incoming gate photon. We study the quantum limit of one incoming gate photon and observe a gain of 20. The gate pulse is stored as a Rydberg excitation in an ultracold gas. The transmission of the subsequent target pulse is suppressed by Rydberg blockade, which is enhanced by a Forster resonance. The detected target photons reveal in a single shot with a fidelity above 0.86 whether a Rydberg excitation was created during the gate pulse. The gain offers the possibility to distribute the transistor output to the inputs of many transistors, thus making complex computational tasks possible. PMID- 25126920 TI - Spectral multiplexing for scalable quantum photonics using an atomic frequency comb quantum memory and feed-forward control. AB - Future multiphoton applications of quantum optics and quantum information science require quantum memories that simultaneously store many photon states, each encoded into a different optical mode, and enable one to select the mapping between any input and a specific retrieved mode during storage. Here we show, with the example of a quantum repeater, how to employ spectrally multiplexed states and memories with fixed storage times that allow such mapping between spectral modes. Furthermore, using a Ti:Tm:LiNbO_{3} waveguide cooled to 3 K, a phase modulator, and a spectral filter, we demonstrate storage followed by the required feed-forward-controlled frequency manipulation with time-bin qubits encoded into up to 26 multiplexed spectral modes and 97% fidelity. PMID- 25126921 TI - PT-symmetric phonon laser. AB - By exploiting recent developments associated with coupled microcavities, we introduce the concept of the PT-symmetric phonon laser with balanced gain and loss. This is accomplished by introducing gain to one of the microcavities such that it balances the passive loss of the other. In the vicinity of the gain-loss balance, a strong nonlinear relation emerges between the intracavity-photon intensity and the input power. This then leads to a giant enhancement of both optical pressure and mechanical gain, resulting in a highly efficient phonon lasing action. These results provide a promising approach for manipulating optomechanical systems through PT-symmetric concepts. Potential applications range from enhancing mechanical cooling to designing phonon-laser amplifiers. PMID- 25126922 TI - Universality of tip singularity formation in freezing water drops. AB - A drop of water deposited on a cold plate freezes into an ice drop with a pointy tip. While this phenomenon clearly finds its origin in the expansion of water upon freezing, a quantitative description of the tip singularity has remained elusive. Here we demonstrate how the geometry of the freezing front, determined by heat transfer considerations, is crucial for the tip formation. We perform systematic measurements of the angles of the conical tip, and reveal the dynamics of the solidification front in a Hele-Shaw geometry. It is found that the cone angle is independent of substrate temperature and wetting angle, suggesting a universal, self-similar mechanism that does not depend on the rate of solidification. We propose a model for the freezing front and derive resulting tip angles analytically, in good agreement with the experiments. PMID- 25126923 TI - Time-reversal-symmetry breaking in turbulence. AB - In three-dimensional turbulent flows, the flux of energy from large to small scales breaks time symmetry. We show here that this irreversibility can be quantified by following the relative motion of several Lagrangian tracers. We find by analytical calculation, numerical analysis, and experimental observation that the existence of the energy flux implies that, at short times, two particles separate temporally slower forwards than backwards, and the difference between forward and backward dispersion grows as t^{3}. We also find the geometric deformation of material volumes, defined by four points spanning an initially regular tetrahedron, to show sensitivity to the time reversal with an effect growing linearly in t. We associate this with the structure of the strain rate in the flow. PMID- 25126924 TI - Entropy- and flow-induced superfluid states. AB - Normally the role of phase fluctuations in superfluids and superconductors is to drive a phase transition to the normal state. This happens due to proliferation of topologically nontrivial phase fluctuations in the form of vortices. Here we discuss a class of systems where, by contrast, nontopological phase fluctuations can produce superfluidity. Here we understand superfluidity as a phenomenon that does not necessarily arises from a broken U(1) symmetry, but can be associated with a certain class of (approximate or exact) degeneracies of the system's energy landscape giving raise to a U(1)-like phase. PMID- 25126925 TI - Anomalous behavior of dark states in quantum gases of (6)Li. AB - We create atom-molecule dark states in a degenerate Fermi gas of ^{6}Li in both weakly and strongly interacting regimes using two-photon Raman scattering to couple fermion pairs to bound molecular states in the ground singlet and triplet potential. Near the unitarity point in the BEC-BCS crossover regime, the atom number revival height associated with the dark state abruptly and unexpectedly decreases and remains low for magnetic fields below the Feshbach resonance center at 832.2 G. With a weakly interacting Fermi gas at 0 G, we perform precision dark state spectroscopy of the least-bound vibrational levels of the lowest singlet and triplet potentials. From these spectra, we obtain binding energies of the v^{''}=9, N^{''}=0 level of the a(1^{3}Sigma_{u}^{+}) potential and the v^{''}=38, N^{''}=0 level of the X(1^{1}Sigma_{g}^{+}) potential with absolute uncertainty as low as 20 kHz. For the triplet potential, we resolve the molecular hyperfine structure. PMID- 25126926 TI - Jumping-catalyst dynamics in nanowire growth. AB - Nanowire growth is generally considered a steady-state process, but oscillatory phenomena are known to often play a fundamental role. Here we identify a natural sequence of distinct growth modes, in two of which the catalyst droplet jumps periodically on and off a crystal facet. The oscillatory modes result from a mismatch between catalyst size and wire diameter; they enable growth of straight smooth-sided wires even when the droplet is too small to span the wire tip. Jumping-catalyst growth modes are seen both in computer simulations of vapor liquid-solid growth, and in movies of Si nanowire growth obtained by in situ microscopy. Our simulations also provide new insight into nanowire kinking. PMID- 25126927 TI - Phase-resolved surface plasmon interferometry of graphene. AB - The surface plasmon polaritons (SPPs) of graphene reflect the microscopic spatial variations of underlying electronic structure and dynamics. Here, we excite and image the graphene SPP response in phase and amplitude by near-field interferometry. We develop an analytic cavity model that can self-consistently describe the SPP response function for edge, grain boundary, and defect SPP reflection and scattering. The derived SPP wave vector, damping, and carrier mobility agree with the results from more complex models. Spatial variations in the Fermi level and associated variations in dopant concentration reveal a nanoscale spatial inhomogeneity in the reduced conductivity at internal boundaries. The additional SPP phase information thus opens a new degree of freedom for spatial and spectral graphene SPP tuning and modulation for optoelectronics applications. PMID- 25126928 TI - Role of dispersion interactions in the polymorphism and entropic stabilization of the aspirin crystal. AB - Aspirin has been used and studied for over a century but has only recently been shown to have an additional polymorphic form, known as form II. Since the two observed solid forms of aspirin are degenerate in terms of lattice energy, kinetic effects have been suggested to determine the metastability of the less abundant form II. Here, first-principles calculations provide an alternative explanation based on free-energy differences at room temperature. The explicit consideration of many-body van der Waals interactions in the free energy demonstrates that the stability of the most abundant form of aspirin is due to a subtle coupling between collective electronic fluctuations and quantized lattice vibrations. In addition, a systematic analysis of the elastic properties of the two forms of aspirin rules out mechanical instability of form II as making it metastable. PMID- 25126929 TI - Semiconducting-to-metallic photoconductivity crossover and temperature-dependent Drude weight in graphene. AB - We investigate the transient photoconductivity of graphene at various gate-tuned carrier densities by optical-pump terahertz-probe spectroscopy. We demonstrate that graphene exhibits semiconducting positive photoconductivity near zero carrier density, which crosses over to metallic negative photoconductivity at high carrier density. These observations can be accounted for by the interplay between photoinduced changes of both the Drude weight and carrier scattering rate. Our findings provide a complete picture to explain the opposite photoconductivity behavior reported in (undoped) graphene grown epitaxially and (doped) graphene grown by chemical vapor deposition. Notably, we observe nonmonotonic fluence dependence of the photoconductivity at low carrier density. This behavior reveals the nonmonotonic temperature dependence of the Drude weight in graphene, a unique property of two-dimensional massless Dirac fermions. PMID- 25126931 TI - Negative oxygen isotope effect on the static spin stripe order in superconducting La(2-x)Ba(x)CuO(4) (x=1/8) observed by muon-spin rotation. AB - Large negative oxygen-isotope (^{16}O and ^{18}O) effects (OIEs) on the static spin-stripe-ordering temperature T_{so} and the magnetic volume fraction V_{m} were observed in La_{2-x}Ba_{x}CuO_{4}(x=1/8) by means of muon-spin-rotation experiments. The corresponding OIE exponents were found to be alpha_{T_{so}}= 0.57(6) and alpha_{V_{m}}=-0.71(9), which are sign reversed to alpha_{T_{c}}=0.46(6) measured for the superconducting transition temperature T_{c}. This indicates that the electron-lattice interaction is involved in the stripe formation and plays an important role in the competition between bulk superconductivity and static stripe order in the cuprates. PMID- 25126930 TI - Sharp low-energy feature in single-particle spectra due to forward scattering in d-wave cuprate superconductors. AB - There is an enormous interest in the renormalization of the quasiparticle (qp) dispersion relation of cuprate superconductors both below and above the critical temperature T_{c} because it enables the determination of the fluctuation spectrum to which the qp's are coupled. A remarkable discovery by angle-resolved photoemission spectroscopy (ARPES) is a sharp low-energy feature (LEF) in qp spectra well below the superconducting energy gap but with its energy increasing in proportion to T_{c} and its intensity increasing sharply below T_{c}. This unexpected feature needs to be reconciled with d-wave superconductivity. Here, we present a quantitative analysis of ARPES data from Bi_{2}Sr_{2}CaCu_{2}O_{8+delta} (Bi2212) using Eliashberg equations to show that the qp scattering rate due to the forward scattering impurities far from the Cu-O planes is modified by the energy gap below T_{c} and shows up as the LEF. This is also a necessary step to analyze ARPES data to reveal the spectrum of fluctuations promoting superconductivity. PMID- 25126932 TI - Scattering matrix formulation of the topological index of interacting fermions in one-dimensional superconductors. AB - We construct a scattering matrix formulation for the topological classification of one-dimensional superconductors with effective time-reversal symmetry in the presence of interactions. For an isolated system, Fidkowski and Kitaev have shown that such systems have a Z_{8} topological classification. We here show that these systems have a unitary scattering matrix at zero temperature when weakly coupled to a normal-metal lead, with a topological index given by the trace of the Andreev-reflection matrix, trr_{he}. With interactions, trr_{he} generically takes on the finite set of values 0, +/-1, +/-2, +/-3, and +/-4. We show that the two topologically equivalent phases with trr_{he}=+/-4 support emergent many-body end states, which we identify to be a topologically protected Kondo-like resonance. The path in phase space that connects these equivalent phases crosses a non-Fermi-liquid fixed point where a multiple-channel Kondo effect develops. Our results connect the topological index to transport properties, thereby highlighting the experimental signatures of interacting topological phases in one dimension. PMID- 25126933 TI - Ultrafast quenching of the exchange interaction in a Mott insulator. AB - We investigate how fast and how effective photocarrier excitation can modify the exchange interaction J_{ex} in the prototype Mott-Hubbard insulator. We demonstrate an ultrafast quenching of J_{ex} both by evaluating exchange integrals from a time-dependent response formalism and by explicitly simulating laser-induced spin precession in an antiferromagnet that is canted by an external magnetic field. In both cases, the electron dynamics is obtained from nonequilibrium dynamical mean-field theory. We find that the modified J_{ex} emerges already within a few electron hopping times after the pulse, with a reduction that is comparable to the effect of chemical doping. PMID- 25126934 TI - Stochastic resonance in collective exciton-polariton excitations inside a GaAs microcavity. AB - We report the first observation of stochastic resonance in confined exciton polaritons. We evidence this phenomena by tracking the polaritons behavior through two stochastic resonance quantifiers namely the spectral magnification factor and the signal-to-noise ratio. The evolution of the stochastic resonance in the function of the modulation amplitude of the periodic excitation signal is studied. Our experimental observations are well reproduced by numerical simulations performed in the framework of the Gross-Pitaevskii equation under stochastic perturbation. PMID- 25126935 TI - Unifying the low-temperature photoluminescence spectra of carbon nanotubes: the role of acoustic phonon confinement. AB - At low temperature the photoluminescence of single-wall carbon nanotubes show a large variety of spectral profiles ranging from ultranarrow lines in suspended nanotubes to broad and asymmetrical line shapes that puzzle the current interpretation in terms of exciton-phonon coupling. Here, we present a complete set of photoluminescence profiles in matrix embedded nanotubes including unprecedented narrow emission lines. We demonstrate that the diversity of the low temperature luminescence profiles in nanotubes originates in tiny modifications of their low-energy acoustic phonon modes. When low-energy modes are locally suppressed, a sharp photoluminescence line as narrow as 0.7 meV is restored. Furthermore, multipeak luminescence profiles with specific temperature dependence show the presence of confined phonon modes. PMID- 25126936 TI - Spin pumping and spin-transfer torques in antiferromagnets. AB - Spin pumping and spin-transfer torques are two reciprocal phenomena widely studied in ferromagnetic materials. However, pumping from antiferromagnets and its relation to current-induced torques have not been explored. By calculating how electrons scatter off a normal metal-antiferromagnetic interface, we derive pumped spin and staggered spin currents in terms of the staggered field, the magnetization, and their rates of change. For both compensated and uncompensated interfaces, spin pumping is of a similar magnitude as in ferromagnets with a direction controlled by the polarization of the driving microwave. The pumped currents are connected to current-induced torques via Onsager reciprocity relations. PMID- 25126937 TI - Ultrafast exciton formation at the ZnO(1010) surface. AB - We study the ultrafast quasiparticle dynamics in and below the ZnO conduction band using femtosecond time-resolved two-photon photoelectron spectroscopy. Above band gap excitation causes hot electron relaxation by electron-phonon scattering down to the Fermi level E_{F} followed by ultrafast (200 fs) formation of a surface exciton (SX). Transient screening of the Coulomb interaction reduces the SX formation probability at high excitation densities near the Mott limit. Located just below the surface, the SX are stable with regard to hydrogen-induced work function modifications and thus the ideal prerequisite for resonant energy transfer applications. PMID- 25126938 TI - Incoherent control of the retinal isomerization in rhodopsin. AB - We propose to control the retinal photoisomerization yield through the backaction dynamics imparted by a nonselective optical measurement of the molecular electronic state. This incoherent effect is easier to implement than comparable coherent pulse shaping techniques, and is also robust to environmental noise. A numerical simulation of the quantum dynamics shows that the isomerization yield of this important biomolecule can be substantially increased above the natural limit. PMID- 25126911 TI - Beam-energy dependence of charge separation along the magnetic field in Au+Au collisions at RHIC. AB - Local parity-odd domains are theorized to form inside a quark-gluon plasma which has been produced in high-energy heavy-ion collisions. The local parity-odd domains manifest themselves as charge separation along the magnetic field axis via the chiral magnetic effect. The experimental observation of charge separation has previously been reported for heavy-ion collisions at the top RHIC energies. In this Letter, we present the results of the beam-energy dependence of the charge correlations in Au+Au collisions at midrapidity for center-of-mass energies of 7.7, 11.5, 19.6, 27, 39, and 62.4 GeV from the STAR experiment. After background subtraction, the signal gradually reduces with decreased beam energy and tends to vanish by 7.7 GeV. This implies the dominance of hadronic interactions over partonic ones at lower collision energies. PMID- 25126939 TI - Effects of cattle management on oak regeneration in northern Californian Mediterranean oak woodlands. AB - Oak woodlands of Mediterranean ecosystems, a major component of biodiversity hotspots in Europe and North America, have undergone significant land-use change in recent centuries, including an increase in grazing intensity due to the widespread presence of cattle. Simultaneously, a decrease in oak regeneration has been observed, suggesting a link between cattle grazing intensity and limited oak regeneration. In this study we examined the effect of cattle grazing on coast live oak (Quercus agrifolia Nee) regeneration in San Francisco Bay Area, California. We studied seedling, sapling and adult density of coast live oak as well as vertebrate herbivory at 8 independent sites under two grazing conditions: with cattle and wildlife presence (n = 4) and only with wildlife (n = 4). The specific questions we addressed are: i) to what extent cattle management practices affect oak density, and ii) what is the effect of rangeland management on herbivory and size of young oak plants. In areas with cattle present, we found a 50% reduction in young oak density, and plant size was smaller, suggesting that survival and growth young plants in those areas are significantly limited. In addition, the presence of cattle raised the probability and intensity of herbivory (a 1.5 and 1.8-fold difference, respectively). These results strongly suggest that the presence of cattle significantly reduced the success of young Q. agrifolia through elevated herbivory. Given the potential impact of reduced recruitment on adult populations, modifying rangeland management practices to reduce cattle grazing pressure seems to be an important intervention to maintain Mediterranean oak woodlands. PMID- 25126941 TI - Growth factor stimulation improves the structure and properties of scaffold-free engineered auricular cartilage constructs. AB - The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-beta1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 um). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation. PMID- 25126940 TI - Selection signatures in worldwide sheep populations. AB - The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of linkage disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows pinpointing several new selection signatures in the sheep genome and distinguishing those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the ones previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments. PMID- 25126942 TI - Thermodynamics of the interaction between Alzheimer's disease related tau protein and DNA. AB - Tau hyperphosphorylation can be considered as one of the hallmarks of Alzheimer's disease and other tauophaties. Besides its well-known role as a microtubule associated protein, Tau displays a key function as a protector of genomic integrity in stress situations. Phosphorylation has been proven to regulate multiple processes including nuclear translocation of Tau. In this contribution, we are addressing the physicochemical nature of DNA-Tau interaction including the plausible influence of phosphorylation. By means of surface plasmon resonance (SPR) we measured the equilibrium constant and the free energy, enthalpy and entropy changes associated to the Tau-DNA complex formation. Our results show that unphosphorylated Tau binding to DNA is reversible. This fact is in agreement with the protective role attributed to nuclear Tau, which stops binding to DNA once the insult is over. According to our thermodynamic data, oscillations in the concentration of dephosphorylated Tau available to DNA must be the variable determining the extent of Tau binding and DNA protection. In addition, thermodynamics of the interaction suggest that hydrophobicity must represent an important contribution to the stability of the Tau-DNA complex. SPR results together with those from Tau expression in HEK cells show that phosphorylation induces changes in Tau protein which prevent it from binding to DNA. The phosphorylation-dependent regulation of DNA binding is analogous to the Tau microtubules binding inhibition induced by phosphorylation. Our results suggest that hydrophobicity may control Tau location and DNA interaction and that impairment of this Tau-DNA interaction, due to Tau hyperphosphorylation, could contribute to Alzheimer's pathogenesis. PMID- 25126943 TI - Toll-like receptor 9-activation during onset of myocardial ischemia does not influence infarct extension. AB - AIM: Myocardial infarction (MI) remains a major cause of death and disability worldwide, despite available reperfusion therapies. Inflammatory signaling is considered nodal in defining final infarct size. Activation of the innate immune receptor toll-like receptors (TLR) 9 prior to ischemia and reperfusion (I/R) reduces infarct size, but the consequence of TLR9 activation timed to the onset of ischemia is not known. METHODS AND RESULTS: The TLR9-agonist; CpG B was injected i.p. in C57BL/6 mice immediately after induction of ischemia (30 minutes). Final infarct size, as well as area-at-risk, was measured after 24 hours of reperfusion. CpG B injection resulted in a significant increase in circulating granulocytes and monocytes both in sham and I/R mice. Paradoxically, clear evidence of reduced cardiac infiltration of both monocytes and granulocytes could be demonstrated in I/R mice treated with CpG B (immunocytochemistry, myeloperoxidase activity and mRNA expression patterns). In addition, systemic TLR9 activation elicited significant alterations of cardiac inflammatory genes. Despite these biochemical and cellular changes, there was no difference in infarct size between vehicle and CpG B treated I/R mice. CONCLUSION: Systemic TLR9-stimulation upon onset of ischemia and subsequent reperfusion does not alter final infarct size despite causing clear alterations of both systemic and cardiac inflammatory parameters. Our results question the clinical usefulness of TLR9 activation during cardiac I/R. PMID- 25126945 TI - Treatment of FANCA cells with resveratrol and N-acetylcysteine: a comparative study. AB - Fanconi anemia (FA) is a genetic disorder characterised by chromosome instability, cytokine ipersensibility, bone marrow failure and abnormal haematopoiesis associated with acute myelogenous leukemia. Recent reports are contributing to characterize the peculiar FA metabolism. Central to these considerations appears that cells from complementation group A (FANCA) display an altered red-ox metabolism. Consequently the possibility to improve FA phenotypical conditions with antioxidants is considered. We have characterized from the structural and biochemical point of view the response of FANCA lymphocytes to N-acetyl-cysteine (NAC) and resveratrol (RV). Surprisingly both NAC and RV failed to revert all the characteristic of FA phenotype and moreover their effects are not super imposable. Our data suggest that we must be aware of the biological effects coming from antioxidant treatment. PMID- 25126946 TI - Development and validation of a prediction score for complications after hepatectomy in hepatitis B-related hepatocellular carcinoma patients. AB - OBJECTIVE AND BACKGROUND: The aim of the present study was to develop and validate a prediction score for postoperative complications by severity and guide perioperative management and patient selection in hepatitis B-related hepatocellular carcinoma patients undergoing liver resection. METHODS: A total of 1543 consecutive liver resections cases were included in the study. Randomly selected sample set of 70% of the study cohort was used to develop a score to predict complications III-V and the remaining 30% was used to validate the score. Based on the preoperative and predictable intraoperative parameters, logistic regression analysis was used to identify risk factors and create an integer score for the predicting of complication. RESULTS: American Society of Anesthesiologists category, portal hypertension, major liver resection (more than 3 segments) and extrahepatic procedures were identified as independent predictors for complications III-V by logistic regression analysis. A score system integrating these 4 factors was stratified into three groups and significantly predicted the risk of complications III-V, with a rate of 1.6%, 11.9% and 65.6% for low, moderate and high risk, respectively. Using the score, the complications risk could be predicted accurately in the validation set, without significant differences between predicted (10.4%) and observed (8.4%) risks for complications III-V (P = 0.466). CONCLUSIONS: Based on four preoperative risk factors, we have developed and validated an integer-based risk score to predict postoperative severe complications after liver resection for hepatitis B-related hepatocellular carcinoma patients in high-volume surgical center. This score may contribute to preoperative risk stratification and clinical decision-making. PMID- 25126948 TI - Association of DNA methyltransferases 3A and 3B polymorphisms, and plasma folate levels with the risk of urothelial carcinoma. AB - BACKGROUND: Interindividual genetic variations of human DNA methyltransferases (DNMTs), which involve the methyl donor from the folate-related one-carbon metabolism pathway, are hypothesized as a risk factor for urothelial carcinoma (UC). Therefore, we evaluated the role of gene-environment interaction in UC carcinogenesis. METHODS: A hospital-based case-control study was conducted by recruiting 192 patients with UC and 381 controls. Their plasma folate levels were measured using a competitive immunoassay kit. In addition, DNMT3A -448A>G and DNMT3B -579G>T genotyping was evaluated using a polymerase chain reaction restriction fragment length polymorphism technique. Multivariate logistic regression and 95% confidence intervals (CIs) were applied to estimate the UC risk. RESULTS: We observed that patients with UC exhibited a higher prevalence rate of folate insufficiency (folate levels <=6 ng/mL) compared with the controls (35.94% and 18.37%, respectively). Furthermore, folate levels were higher in the prevalent UC patients than in the incident UC patients. However, folate insufficiency was similarly associated with a nearly two-fold increase in the risk of UC regardless of the UC patient group. In addition, the frequencies of the variant alleles for DNMT3A and DNMT3B were 0.80 and 0.92, respectively, and no association was observed with UC risk. However, participants with a variant homozygous genotype of DNMT3B -579G>T and folate insufficiency or with high cumulative cigarette smoking exhibited an increased risk of UC. CONCLUSION: Overall, environmental factors may contribute more significantly to UC carcinogenesis compared with genetic susceptibility. Future studies should investigate other polymorphisms of DNMT3A and DNMT3B to determine genetic susceptibility. PMID- 25126947 TI - Brain networks during free viewing of complex erotic movie: new insights on psychogenic erectile dysfunction. AB - Psychogenic erectile dysfunction (ED) is defined as a male sexual dysfunction characterized by a persistent or recurrent inability to attain adequate penile erection due predominantly or exclusively to psychological or interpersonal factors. Previous fMRI studies were based on the common occurrence in the male sexual behaviour represented by the sexual arousal and penile erection related to viewing of erotic movies. However, there is no experimental evidence of altered brain networks in psychogenic ED patients (EDp). Some studies showed that fMRI activity collected during non sexual movie viewing can be analyzed in a reliable manner with independent component analysis (ICA) and that the resulting brain networks are consistent with previous resting state neuroimaging studies. In the present study, we investigated the modification of the brain networks in EDp compared to healthy controls (HC), using whole-brain fMRI during free viewing of an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan evaluation, psychiatric, and general medical evaluations. The performed ICA showed that visual network (VN), default-mode network (DMN), fronto-parietal network (FPN) and salience network (SN) were spatially consistent across EDp and HC. However, between-group differences in functional connectivity were observed in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in the inferior parietal lobes, posterior cingulate cortex and medial prefrontal cortex, whereas in the SN decreased and increased connectivity was observed in the right insula and in the anterior cingulate cortex respectively. The decreased levels of intrinsic functional connectivity principally involved the subsystem of DMN relevant for the self relevant mental simulation that concerns remembering of past experiences, thinking to the future and conceiving the viewpoint of the other's actions. Moreover, the between group differences in the SN nodes suggested a decreased recognition of autonomical and sexual arousal changes in EDp. PMID- 25126949 TI - Symptomatic and incidental venous thromboembolic disease are both associated with mortality in patients with prostate cancer. AB - INTRODUCTION: The association between malignancy and venous thromboembolic disease (VTE) is well established. The independent impact of VTE, both symptomatic and incidental, on survival in patients with prostate cancer is not known. We conducted a retrospective cohort study to evaluate the effect of VTE of survival in prostate cancer. METHODS: Data regarding clinical characteristics, treatment and outcomes of 453 consecutive prostate cancer patients were collected. Fisher exact (categorical variables) and t-test (continuous variables) were utilized to test associations with VTE and mortality. Survival was estimated using the Kaplan Meier method. A Cox regression model was used to model the mortality hazard ratio (HR). RESULTS: At diagnosis, 358 (83%) patients had early stage disease, 43 (10%) had locally advanced disease and 32 (7%) had metastatic disease. During the follow up period, 122 (27%) patients died and 41 (9%) developed VTE (33 deep vein thrombosis, 5 pulmonary embolism, and 3 patients with both DVT and PE). Twenty-five VTE events were symptomatic and 16 were incidentally diagnosed on CT scans obtained for other reasons. VTE was associated with increased mortality [HR 6.89 (4.29-11.08), p<0.001] in a multivariable analysis adjusted for cancer stage, performance status, treatments and co morbidities. There was no difference in survival between patients who had symptomatic and incidental VTE. CONCLUSION: Venous thromboembolic disease, both symptomatic and incidental, is a predictor of poor survival in patients with prostate cancer, especially those with advanced disease. Further studies are needed to evaluate the benefit of prophylactic and therapeutic anticoagulation in this population. PMID- 25126950 TI - Aspirin delimits platelet life span by proteasomal inhibition. AB - Aspirin is widely used in clinical settings as an anti-inflammatory and anti platelet drug due its inhibitory effect on cyclooxygenase activity. Although the drug has long been considered to be an effective and safe therapeutic regime against inflammatory and cardiovascular disorders, consequences of its cyclooxygenase-independent attributes on platelets, the key players in thrombogenesis, beg serious investigation. In this report we explored the effect of aspirin on platelet lifespan in murine model and its possible cytotoxicity against human platelets in vitro. Aspirin administration in mice led to significant reduction in half-life of circulating platelets, indicative of enhanced rate of platelet clearance. Aspirin-treated human platelets were found to be phagocytosed more efficiently by macrophages, associated with attenuation in platelet proteasomal activity and upregulation of conformationally active Bax, which were consistent with enhanced platelet apoptosis. Although the dosage of aspirin administered in mice was higher than the therapeutic regimen against cardiovascular events, it is comparable with the recommended anti-inflammatory prescription. Thus, above observations provide cautionary framework to critically re-evaluate prophylactic and therapeutic dosage regime of aspirin in systemic inflammatory as well as cardiovascular ailments. PMID- 25126951 TI - Positive feedback promotes oscillations in negative feedback loops. AB - A simple three-component negative feedback loop is a recurring motif in biochemical oscillators. This motif oscillates as it has the three necessary ingredients for oscillations: a three-step delay, negative feedback, and nonlinearity in the loop. However, to oscillate, this motif under the common Goodwin formulation requires a high degree of cooperativity (a measure of nonlinearity) in the feedback that is biologically "unlikely." Moreover, this recurring negative feedback motif is commonly observed augmented by positive feedback interactions. Here we show that these positive feedback interactions promote oscillation at lower degrees of cooperativity, and we can thus unify several common kinetic mechanisms that facilitate oscillations, such as self activation and Michaelis-Menten degradation. The positive feedback loops are most beneficial when acting on the shortest lived component, where they function by balancing the lifetimes of the different components. The benefits of multiple positive feedback interactions are cumulative for a majority of situations considered, when benefits are measured by the reduction in the cooperativity required to oscillate. These positive feedback motifs also allow oscillations with longer periods than that determined by the lifetimes of the components alone. We can therefore conjecture that these positive feedback loops have evolved to facilitate oscillations at lower, kinetically achievable, degrees of cooperativity. Finally, we discuss the implications of our conclusions on the mammalian molecular clock, a system modeled extensively based on the three component negative feedback loop. PMID- 25126952 TI - Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets. AB - Single- or few-layered transitional metal dichalcogenides, as a new genus of two dimensional nanomaterials, have attracted tremendous attention in recent years, owing to their various intriguing properties. In this study, chemically exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in physiological solutions and no obvious toxicity. Taking advantage of its ultra high surface area, the obtained MoS2-PEG is able to load a photodynamic agent, chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6 after being loaded on MoS2-PEG shows remarkably increased cellular uptake and thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2 PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal experiments. Our study presents a new type of multifunctional nanocarrier for the delivery of photodynamic therapy, which, if combined with photothermal therapy, appears to be an effective therapeutic approach for cancer treatment. PMID- 25126953 TI - Differential activity of Striga hermonthica seed germination stimulants and Gigaspora rosea hyphal branching factors in rice and their contribution to underground communication. AB - Strigolactones (SLs) trigger germination of parasitic plant seeds and hyphal branching of symbiotic arbuscular mycorrhizal (AM) fungi. There is extensive structural variation in SLs and plants usually produce blends of different SLs. The structural variation among natural SLs has been shown to impact their biological activity as hyphal branching and parasitic plant seed germination stimulants. In this study, rice root exudates were fractioned by HPLC. The resulting fractions were analyzed by MRM-LC-MS to investigate the presence of SLs and tested using bioassays to assess their Striga hermonthica seed germination and Gigaspora rosea hyphal branching stimulatory activities. A substantial number of active fractions were revealed often with very different effect on seed germination and hyphal branching. Fractions containing (-)-orobanchol and ent-2' epi-5-deoxystrigol contributed little to the induction of S. hermonthica seed germination but strongly stimulated AM fungal hyphal branching. Three SLs in one fraction, putative methoxy-5-deoxystrigol isomers, had moderate seed germination and hyphal branching inducing activity. Two fractions contained strong germination stimulants but displayed only modest hyphal branching activity. We provide evidence that these stimulants are likely SLs although no SL representative masses could be detected using MRM-LC-MS. Our results show that seed germination and hyphal branching are induced to very different extents by the various SLs (or other stimulants) present in rice root exudates. We propose that the development of rice varieties with different SL composition is a promising strategy to reduce parasitic plant infestation while maintaining symbiosis with AM fungi. PMID- 25126954 TI - Gynecologic Cancer InterGroup (GCIG) consensus review for squamous cell carcinoma of the ovary. AB - Squamous cell carcinoma of the ovary is a rare complication of mature cystic teratoma. The epidemiology, pathology, diagnosis, and management of this rare tumor are reviewed. Clinical characteristics, preoperative imaging, and tumor markers may help to predict malignancy preoperatively. Complete cytoreduction should be the aim of surgery. The prognosis for stage 1A disease is good, but for women with advanced or recurrent disease, it is very poor and has not improved in recent years. At present, there are insufficient data to provide clear guidance on the optimal management strategy for advanced disease, and there is a need to gain an understanding of the biology and to develop novel effective therapies. This will require coordinated international collaboration. PMID- 25126955 TI - Is removing 9 lymph nodes a correct cutoff to define optimal lymphadenectomy?: The open question of lymph node count. PMID- 25126956 TI - The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative systematic review. AB - INTRODUCTION: Homeobox genes are often deregulated in cancer. They can have both oncogenic and tumor-suppressing potential. The Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor. It is implicated in differentiation, proliferation, cell-adhesion, and migration. CDX2 has been proposed as a tumor suppressor in colorectal cancer but its role is still controversial. This systematic review were undertaken in order to clarify CDX2s role in colorectal cancer. METHODS: A literature search was performed in the MEDLINE database from 1966 to February 2014. Only studies in which all or a part of the experimental design were performed on human colorectal cancer tissue were included. Thus, studies solely performed in cell-lines or animal models were excluded. RESULTS: Fifty-two articles of relevance were identified. CDX2 expression was rarely lost in colorectal cancers, however the expression pattern may often be heterogeneous within the tumor and can be selectively down regulated at the invasive front and in tumor buddings. Loss of CDX2 expression is probably correlated to tumor grade, stage, right-sided tumor location, MMR-deficiency, CIMP, and BRAF mutations. The CDX2 gene is rarely mutated but the locus harboring the gene is often amplified and may suggest CDX2 as a linage-survival oncogene. CDX2 might be implicated in cell proliferation and migration through cross-talk with the Wnt-signaling pathway, tumor-stroma proteins, and inflammatory cytokines. CONCLUSION: A clear role for CDX2 expression in colorectal cancer remains to be elucidated, and it might differ in relation to the underlying molecular pathways leading to the cancer formation. PMID- 25126957 TI - A double-blind, placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women. AB - Obesity, the global epidemic health problem, results in chronic disorders. Melatonin supplementation may prevent the adverse health consequences of obesity. The aim of this study was to assess the effects of melatonin supplementation on inflammatory and oxidative stress parameters in obese women. In randomized, double-blind, placebo-controlled trial, 44 obese women were randomly assigned to melatonin (n=22) and placebo (n=22) groups. Subjects were supplemented with a daily dose of 6 mg melatonin or placebo with low calorie diet for 40 days. Serum TNF-alpha, IL-6, hsCRP, TAC, and MDA levels were assessed before and after intervention. In the melatonin group, mean serum TNF-alpha, IL-6, hsCRP, and MDA levels decreased significantly (p<0.05) from 3.52+/-0.72 pg/ml, 27.12+/-6.32 pg/ml, 2.54+/-0.49 mg/l, and 3.81+/-0.29 nmol/l to 1.73+/-0.07, 16.34+/-6.32, 1.67+/-0.27, and 2.79+/-0.29, respectively. Whilst in the placebo group the decrease in values were not statistically significant. Mean TAC level increased slightly (from 1.11+/-0.30 to 1.14+/-0.45 mmol/l) in the melatonin group whereas it decreased slightly (from 1.13+/-0.15 to 1.08+/-0.21 nmol/l) in the placebo group. Significant differences were observed only for TNF-alpha (p=0.02) and IL-6 (p=0.03) between the 2 study groups. Considering the improvements in inflammatory and oxidative stress factors in obese women, it seems that melatonin supplementation may provide beneficial effects in obesity treatment by ameliorating some of its complications. However, further studies are needed to make concise conclusions. PMID- 25126958 TI - Crystal structure of the homology domain of the eukaryotic DNA replication proteins Sld3/Treslin. AB - The initiation of eukaryotic chromosomal DNA replication requires the formation of an active replicative helicase at the replication origins of chromosomal DNA. Yeast Sld3 and its metazoan counterpart Treslin are the hub proteins mediating protein associations critical for the helicase formation. Here, we show the crystal structure of the central domain of Sld3 that is conserved in Sld3/Treslin family of proteins. The domain consists of two segments with 12 helices and is sufficient to bind to Cdc45, the essential helicase component. The structure model of the Sld3-Cdc45 complex, which is crucial for the formation of the active helicase, is proposed. PMID- 25126959 TI - Structural basis for the SOX-dependent genomic redistribution of OCT4 in stem cell differentiation. AB - In pluripotent cells, OCT4 associates with SOX2 to maintain pluripotency or with SOX17 to induce primitive endoderm commitment. The OCT4-SOX2 and OCT4-SOX17 combinations bind mutually exclusive to two distinct composite DNA elements, known as the "canonical" and "compressed" motifs, respectively. The structural basis for the OCT4-SOX17 cooperativity is unknown. Whereas SOX17 has been engineered to replace SOX2 in the pluripotency circuitry, all generated SOX2 mutants have failed to act like SOX17. From molecular simulations, we revealed the OCT4-SOX17 interaction interface and elucidated the SOX-dependent motif preference of OCT4. Moreover, we designed a SOX2 mutant that we predicted and confirmed experimentally to bind cooperatively with OCT4 to the compressed motif. Ultimately, we found a strong correlation between the experimental and calculated relative cooperative-binding free energies of 12 OCT4-SOX-DNA complexes. Therefore, we validated the OCT4-SOX interfaces and demonstrated that in silico design of DNA-binding cooperativity is suitable for altering transcriptional circuitries. PMID- 25126961 TI - Circuit topology of proteins and nucleic acids. AB - Folded biomolecules display a bewildering structural complexity and diversity. They have therefore been analyzed in terms of generic topological features. For instance, folded proteins may be knotted, have beta-strands arranged into a Greek key motif, or display high contact order. In this perspective, we present a method to formally describe the topology of all folded linear chains and hence provide a general classification and analysis framework for a range of biomolecules. Moreover, by identifying the fundamental rules that intrachain contacts must obey, the method establishes the topological constraints of folded linear chains. We also briefly illustrate how this circuit topology notion can be applied to study the equivalence of folded chains, the engineering of artificial RNA structures and DNA origami, the topological structure of genomes, and the role of topology in protein folding. PMID- 25126962 TI - Comprehension asymmetries in language acquisition: a test for Relativized Minimality. AB - Cross-linguistic studies have shown that typically developing children have difficulties comprehending non-canonical structures. These findings have been interpreted within the Relativized Minimality (RM) approach, according to which local relations cannot be established between two terms of a dependency if an intervening element possesses similar morphosyntactic features. In an extension of RM, Friedmann, Belletti, and Rizzi (2009) suggested that lexical NP restriction is the source of minimality effects in non-canonical sentences. The present study aimed at investigating whether the predictions of their account can be confirmed in Greek. Our results indicate that although lexical NP restriction is a crucial factor in generating minimality effects, it is not always sufficient to account for the comprehension difficulties that young children face with non canonical sentences, since the internal structure (i.e. the feature specification) of the moved element and of the intervener affects their performance, as well. PMID- 25126960 TI - The structure of mouse cytomegalovirus m04 protein obtained from sparse NMR data reveals a conserved fold of the m02-m06 viral immune modulator family. AB - Immunoevasins are key proteins used by viruses to subvert host immune responses. Determining their high-resolution structures is key to understanding virus-host interactions toward the design of vaccines and other antiviral therapies. Mouse cytomegalovirus encodes a unique set of immunoevasins, the m02-m06 family, that modulates major histocompatibility complex class I (MHC-I) antigen presentation to CD8+ T cells and natural killer cells. Notwithstanding the large number of genetic and functional studies, the structural biology of immunoevasins remains incompletely understood, largely because of crystallization bottlenecks. Here we implement a technology using sparse nuclear magnetic resonance data and integrative Rosetta modeling to determine the structure of the m04/gp34 immunoevasin extracellular domain. The structure reveals a beta fold that is representative of the m02-m06 family of viral proteins, several of which are known to bind MHC-I molecules and interfere with antigen presentation, suggesting its role as a diversified immune regulation module. PMID- 25126963 TI - Comprehensive approach to systemic sclerosis patients during pregnancy. AB - Systemic sclerosis (SSc) is a connective tissue disease that usually affects women, with a male:female ratio of 1:4-10. It was thought that there was a prohibitive risk of fatal complications in the pregnancies of patients with SSc. It is now known that the majority of these women undergo a normal progression of pregnancy if the right time is chosen and a close obstetric care is delivered. The obstetric risk will depend on the subtype and clinical stage of the disease, and the presence and severity of the internal organ involvement during the pregnancy. The management of these pregnancies should be provided in a specialized center, with a multidisciplinary team capable of identifying and promptly treating complications. Treatment should be limited to drugs with no teratogenic potential, except when renal crises or severe cardiovascular complications develop. PMID- 25126965 TI - Evidence-based care for trilateral retinoblastoma. PMID- 25126964 TI - Trilateral retinoblastoma: a systematic review and meta-analysis. AB - BACKGROUND: About 5% of children with retinoblastoma from germline mutation of the RB1 gene are at risk of developing trilateral retinoblastoma--intraocular retinoblastoma combined with a histologically similar brain tumour, most commonly in the pineal gland. We aimed to provide a systematic overview of published data for trilateral retinoblastoma, and to analyse how survival has changed. METHODS: We searched Medline and Embase for scientific literature published between Jan 1, 1966, and April 14, 2014, that assessed trilateral retinoblastoma cases. We undertook a meta-analysis of survival with the Kaplan-Meier method and Cox proportional hazards regression, stratified on the basis of the original study, to account for between-study heterogeneity. FINDINGS: We included 90 studies, with 174 patients with trilateral retinoblastoma. 5-year survival after pineal trilateral retinoblastoma increased from 6% (95% CI 2-15) in patients diagnosed before 1995, to 44% (26-61; p<0.0001) in those diagnosed from 1995 onwards. Before 1995, no patients with non-pineal trilateral retinoblastoma survived, but from 1995 onwards, 5-year survival was 57% (30-77; p=0.035). Hazard ratios (HR) adjusted for the presence of leptomeningeal metastases and trilateral retinoblastoma location, suggested that both conventional (HR 0.059, 95% CI 0.016 0.226; p<0.0001) and high-dose chemotherapy with stem-cell rescue (0.013, 0.002 0.064; p<0.0001) most strongly contributed to this improvement. Absence of leptomeningeal metastases (HR 2.13, 95% CI 0.98-4.60; p=0.055) were associated with improved survival. Non-pineal trilateral retinoblastomas were larger than pineal tumours (median 30 mm [range 6-100] vs 22 mm [7-60]; p=0.012), but both had similar outcomes since 1995. INTERPRETATION: Our results suggest that improvements in overall survival are attributable to improved chemotherapy regimens and early detection of pineal trilateral retinoblastoma. As such, successful treatment of trilateral retinoblastoma should include screening at least at the time of retinoblastoma diagnosis and chemotherapy, which would preferably be a high-dose regimen with autologous stem-cell rescue. FUNDING: None. PMID- 25126966 TI - Solid-phase dispersive extraction method for analysis of benzodiazepine drugs in serum and urine samples. AB - A simple yet highly efficient pretreatment method called solid-phase dispersive extraction (SPDE) was developed and used in combination with liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS) for the analysis of benzodiazepines (BZPs) in serum and urine samples. By using a custom-made centrifugal filter, SPDE could be performed in a closed system, thereby minimizing exposure to infectious microbes or hazardous chemicals. The limit of detection and the limit of quantification of nine BZPs were 1-10 and 5-50ng/mL, respectively. The average recoveries of BZPs from pooled serum samples spiked at 50 and 500ng/mL were 89.6-105.0% (RSD: 2.1-6.8%) and 93.6-110.4% (RSD: 2.1-4.2%), respectively, and those from urine samples were 88.7-105.5% (RSD: 2.9-6.4%) and 91.5-101.1% (RSD: 3.6-5.5%), respectively. SPDE-LC/TOF-MS has potential application in forensic science and emergency medicine. PMID- 25126968 TI - Development of a selective agar plate for the detection of Campylobacter spp. in fresh produce. AB - This study was conducted to develop a selective medium for the detection of Campylobacter spp. in fresh produce. Campylobacter spp. (n=4), non-Campylobacter (showing positive results on Campylobacter selective agar) strains (n=49) isolated from fresh produce, indicator bacteria (n=13), and spoilage bacteria isolated from fresh produce (n=15) were plated on four Campylobacter selective media. Bolton agar and modified charcoal cefoperazone deoxycholate agar (mCCDA) exhibited higher sensitivity for Campylobacter spp. than did Preston agar and Hunt agar, although certain non-Campylobacter strains isolated from fresh produce by using a selective agar isolation method, were still able to grow on Bolton agar and mCCDA. To inhibit the growth of non-Campylobacter strains, Bolton agar and mCCDA were supplemented with 5 antibiotics (rifampicin, polymyxin B, sodium metabisulfite, sodium pyruvate, ferrous sulfate) and the growth of Campylobacter spp. (n=7) and non-Campylobacter strains (n=44) was evaluated. Although Bolton agar supplemented with rifampicin (BR agar) exhibited a higher selectivity for Campylobacter spp. than did mCCDA supplemented with antibiotics, certain non Campylobacter strains were still able to grow on BR agar (18.8%). When BR agar with various concentrations of sulfamethoxazole-trimethoprim were tested with Campylobacter spp. (n=8) and non-Campylobacter (n=7), sulfamethoxazole trimethoprim was inhibitory against 3 of 7 non-Campylobacter strains. Finally, we validated the use of BR agar containing 50mg/L sulfamethoxazole (BRS agar) or 0.5mg/L ciprofloxacin (BRCS agar) and other selective agars for the detection of Campylobacter spp. in chicken and fresh produce. All chicken samples were positive for Campylobacter spp. when tested on mCCDA, BR agar, and BRS agar. In fresh produce samples, BRS agar exhibited the highest selectivity for Campylobacter spp., demonstrating its suitability for the detection of Campylobacter spp. in fresh produce. PMID- 25126969 TI - Exploring the role of parents and peers in young adolescents' risk taking on social networking sites. AB - This study investigated the role of parental and peer mediation in young adolescents' engagement in risk-taking in social networking sites (SNSs). A survey conducted in Malaysia with 469 SNS users aged 13-14 revealed that control based parental mediation can cause boomerang effects, making young adolescents more inclined to taking risks in SNSs. While discussion-based parental mediation was found to be negatively related to young adolescents' befriending strangers in SNSs, it did not reduce privacy risks. Findings also suggested that peer influence could result in undesirable outcomes. In particular, the more young adolescents talked about Internet-related issues with peers, the more likely they were to disclose personally identifiable information on SNSs. PMID- 25126970 TI - Response to the letter by Olivier Barbier, Didier Ollat, Gilbert Versier. PMID- 25126967 TI - Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac. AB - We examined whether nerve growth factor (NGF), an inflammatory mediator that contributes to chronic hypersensitivity, alters the intracellular signaling that mediates the sensitizing actions of PGE2 from activation of protein kinase A (PKA) to exchange proteins directly activated by cAMP (Epacs). When isolated sensory neurons are grown in the absence of added NGF, but not in cultures grown with 30 ng/ml NGF, inhibiting protein kinase A (PKA) activity blocks the ability of PGE2 to augment capsaicin-evoked release of the neuropeptide CGRP and to increase the number of action potentials (APs) evoked by a ramp of current. Growing sensory neurons in culture in the presence of increasing concentrations of NGF increases the expression of Epac2, but not Epac1. An intradermal injection of complete Freund's adjuvant into the rat hindpaw also increases the expression of Epac2, but not Epac1 in the dorsal root ganglia and spinal cord: an effect blocked by intraplantar administration of NGF antibodies. Treating cultures grown in the presence of 30 ng/ml NGF with Epac1siRNA significantly reduced the expression of Epac1, but not Epac2, and did not block the ability of PGE2 to augment capsaicin-evoked release of CGRP from sensory neurons. Exposing neuronal cultures grown in NGF to Epac2siRNAreduced the expression of Epac2, but not Epac1 and prevented the PGE2-induced augmentation of capsaicin and potassium-evoked CGRP release in sensory neurons and the PGE2-induced increase in the number of APs generated by a ramp of current. In neurons grown with no added NGF, Epac siRNAs did not attenuate PGE2-induced sensitization. These results demonstrate that NGF, through increasing Epac2 expression, alters the signaling cascade that mediates PGE2-induced sensitization of sensory neurons, thus providing a novel mechanism for maintaining PGE2-induced hypersensitivity during inflammation. PMID- 25126971 TI - Adoption of the 16-month American Board of Radiology pathway to dual board certifications in nuclear radiology and/or nuclear medicine for diagnostic radiology residents. AB - RATIONALE AND OBJECTIVES: In 2010, the American Board of Radiology (ABR) approved a new 16-month nuclear subspecialty training pathway within a standard 48-month Accreditation Council for Graduate Medical Education (ACGME)-accredited diagnostic radiology (DR) residency available to institutions sponsoring ACGME accredited nuclear radiology (NR) and/or nuclear medicine (NM) program(s). This accelerated pathway leads to eligibility for dual ABR certifications in DR and NR or in NM by the American Board of Nuclear Medicine (ABNM). The American College of Radiology, in conjunction with the ABR, aimed to understand adoption of this new pathway, barriers to implementation, preferences for subspecialty certification, and competing alternative combined DR/NR/NM training pathways. MATERIALS AND METHODS: During 2013-2014, there were 20 ACGME-accredited NR fellowship and 43 ACGME-accredited NM residency programs eligible to adopt this new 16-month pathway. They were surveyed by e-mail correspondence regarding implementation and barriers to implementation, board certification (ABR-NR and ABNM) preferences, and local alternative training pathways. RESULTS: With 100% of the surveys completed, a small cadre of qualifying DR programs (14, 22%) has adopted (9, 14%) or is seriously considering adopting (5, 8%) the 16-month ABR pathway. For most, implementation is problematic with numerous barriers in common. Five (8%) institutions are developing 60-month nontraditional models as alternative routes to ABR-DR/ABR-NR certifications and/or dual ABR/ABNM board certifications. CONCLUSIONS: In spite of strategies to promote a shortened training pathway in NR/NM, traditional subspecialty fellowships outside the DR residency remain the dominant pathway leading to ABR subspecialty certification in NR and/or ABNM certification for diagnostic radiologists. PMID- 25126972 TI - Intrapleural fluid infusion for MR-guided high-intensity focused ultrasound ablation in the liver dome. AB - RATIONALE AND OBJECTIVES: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation of tumors in the liver dome is challenging because of the presence of air in the costophrenic angle. In this study, we used a porcine liver model and a clinical MR-HIFU system to assess the feasibility and safety of using intrapleural fluid infusion (IPI) to create an acoustic window for MR-HIFU ablation in the liver dome. MATERIALS AND METHODS: Healthy adult Dalland land pigs (n = 6) under general anesthesia were used with animal committee approval. Degassed saline (200-800 mL) was infused into the intrapleural space under ultrasound guidance. A clinical 1.5-T MR-HIFU system was used to perform sonications (4-mm treatment cells, 300-450 W, 20-30 seconds) in the liver dome under real-time MR thermometry. An intercostal firing technique was used to prevent rib heating in one experiment. Technical success was defined as a temperature increase (>10 degrees C) in the target area. After termination, the animal was examined for thermal damage to liver, diaphragm, pleura, lung, or intercostal muscle. RESULTS: An acoustic window was established in all animals. A temperature increase in the target area was achieved in all animals (max. 47 degrees C-67 degrees C). MR thermometry showed no heating outside the target area. Intercostal firing effectively reduced rib heating (55 degrees C vs. 42 degrees C). Postmortem examination revealed no unwanted thermal damage. One complication occurred, in the first experiment, because of an ill-suited needle (displacement of the needle). CONCLUSIONS: The results indicate that IPI may be used safely to assist MR-HIFU ablation of tumors in the liver dome. For reliable tissue coagulation, IPI must be combined with an intercostal sonication technique. Considering the proportion of patients with tumors in the liver dome, IPI widens the applicability of MR-HIFU ablation for liver tumors considerably. PMID- 25126973 TI - Breast MRI BI-RADS assessments and abnormal interpretation rates by clinical indication in US community practices. AB - RATIONALE AND OBJECTIVES: As breast magnetic resonance imaging (MRI) use grows, benchmark performance parameters are needed for auditing and quality assurance purposes. We describe the variation in breast MRI abnormal interpretation rates (AIRs) by clinical indication among a large sample of US community practices. MATERIALS AND METHODS: We analyzed data from 41 facilities across five Breast Cancer Surveillance Consortium imaging registries. Each registry obtained institutional review board approval for this Health Insurance Portability and Accountability Act compliant analysis. We included 11,654 breast MRI examinations conducted in 2005-2010 among women aged 18-79 years. We categorized clinical indications as 1) screening, 2) extent of disease, 3) diagnostic (eg, breast symptoms), and 4) other (eg, short-interval follow-up). We characterized assessments as positive (ie, Breast Imaging Reporting and Data System [BI-RADS] 0, 4, and 5) or negative (ie, BI-RADS 1, 2, and 6) and provide results with BI RADS 3 categorized as positive and negative. We tested for differences in AIRs across clinical indications both unadjusted and adjusted for patient characteristics and registry and assessed for changes in AIRs by year within each clinical indication. RESULTS: When categorizing BI-RADS 3 as positive, AIRs were 21.0% (95% confidence interval [CI], 19.8-22.3) for screening, 31.7% (95% CI, 29.6-33.8) for extent of disease, 29.7% (95% CI, 28.3-31.1) for diagnostic, and 27.4% (95% CI, 25.0-29.8) for other indications (P < .0001). When categorizing BI RADS 3 as negative, AIRs were 10.5% (95% CI, 9.5-11.4) for screening, 21.8% (95% CI, 19.9-23.6) for extent of disease, 17.7% (95% CI, 16.5-18.8) for diagnostic, and 13.3% (95% CI, 11.6-15.2) for other indications (P < .0001). The significant differences in AIRs by indication persisted even after adjusting for patient characteristics and registry (P < .0001). In addition, for most indications, there were no significant changes in AIRs over time. CONCLUSIONS: Breast MRI AIRs differ significantly by clinical indication. Practices should stratify breast MRI examinations by indication for quality assurance and auditing purposes. PMID- 25126974 TI - Comparison between multivolume CT-based surrogates of regional ventilation in healthy subjects. AB - RATIONALE AND OBJECTIVES: The assessment of regional ventilation is of critical importance when investigating lung function during disease progression and planning of pulmonary interventions. Recently, different computed tomography (CT) based parameters have been proposed as surrogates of lung ventilation. The aim of the present study was to compare these parameters, namely variations of density (DeltaHU), specific volume (sVol), and specific gas volume (DeltaSVg) between different lung volumes, in relation to their topographic distribution within the lung. MATERIALS AND METHODS: Ten healthy volunteers were scanned via high resolution CT at residual volume (RV) and total lung capacity (TLC); DeltaHU, sVol, and DeltaSVg were mapped voxel by voxel after registering TLC onto RV. Variations of the three parameters along the vertical and horizontal directions were analyzed. RESULTS: Along the vertical direction (from ventral to dorsal regions), a strong dependence on gravity was found in DeltaHU and sVol, with greater values in the dorsal regions of the lung (P < .001), whereas DeltaSVg was more homogeneously distributed within the lung. Conversely, along the caudocranial direction (from lung bases to apexes) where no gravitational gradient is present, the three parameters behaved similarly, with lower values at the apices. CONCLUSIONS: DeltaHU, sVol, and DeltaSVg behave differently along the gravity direction. As the greater amount of air delivered to the dependent portion of the lung supplies a larger number of alveoli, the amount of gas delivered to alveoli compared to the mass of tissue is not gravity dependent. The minimization of gravity dependence in the distribution of ventilation when using DeltaSVg suggests that this parameter is more reliable to discriminate healthy from pathologic regions. PMID- 25126976 TI - Environmental sampling for Clostridium difficile on alcohol-based hand rub dispensers in an academic medical center. AB - BACKGROUND: Clostridum difficile is a gram-positive, spore-forming anaerobic bacillus that has substantial associated morbidity, mortality, and associated healthcare burdens. Clostridium difficile spores are not destroyed by alcohol. Alcohol gel dispensers are used commonly as the hand sanitization method of choice in hospitals. It is possible that gel dispensers are fomites for C. difficile. METHODS: Thirty alcohol-based gel dispenser handles outside of rooms of patients with active C. difficile infection were sampled. The samples were assessed for C. difficile by both culture and polymerase chain reaction (PCR). The samples were also assessed for other organisms by culture. RESULTS: No C. difficile was cultured or detected by PCR on any of the gel dispensers. Coagulase negative Staphyloccus spp., diptheroids, and Bacillus spp. were the organisms detected most commonly. CONCLUSION: At our institution, C. difficile is not present on alcohol-based gel dispensers, but other potentially pathogenis are. PMID- 25126975 TI - A pharmacogenetics-based warfarin maintenance dosing algorithm from Northern Chinese patients. AB - Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n = 551), warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2 rs2108622 (0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for 45.1% of the warfarin dose variability. In the validation cohort (n = 236), the actual maintenance dose was significantly correlated with predicted dose (r = 0.609, P<0.001). Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients. PMID- 25126977 TI - Preventing intraperitoneal adhesions with ethyl pyruvate and hyaluronic acid/carboxymethylcellulose: a comparative study in an experimental model. AB - OBJECTIVE: To compare the effectiveness of ethyl pyruvate (EP) with that of hyaluronic acid+carboxymethyl cellulose (Seprafilm) for the prevention of intraperitoneal adhesions. Seprafilm has been shown to be effective in many experimental and clinical studies. STUDY DESIGN: Thirty rats were divided into three groups at random, and uterine horn abrasion was performed by laparotomy. One group received no treatment (control group), one group received a single intraperitoneal dose of EP 50mg/kg (EP group), and a 2*1-cm patch of Seprafilm was applied in the third group (Seprafilm group). All rats were killed 14 days after surgery. Macroscopic and histopathological evaluation were performed by a surgeon and a pathologist who were blinded to group allocation. Histopathologically, inflammation, fibroblastic activity, foreign body reaction, collagen proliferation, vascular proliferation, Masson-Trichrome score, matrix metalloproteinase-2 score and vascular endothelial growth factor score were studied. RESULTS: Median macroscopic intraperitoneal adhesion scores for the control, EP and Seprafilm groups were 2.8, 1.2 and 1.1, respectively. Multiple comparisons between groups showed a significant difference (p<0.05). In binary comparisons, significant differences were found between the control group and the EP group, and between the control group and the Seprafilm group (p<0.05). No significant difference was found between the adhesion scores for the EP group and the Seprafilm group (p>0.05). After histopathological evaluation, significant differences in all parameters were found between the groups (p<0.05). In the paired comparison, significant differences were found between the control group and the EP group, and between the control group and the Seprafilm group (p<0.0167), but no significant difference was found between the EP group and the Seprafilm group (p>0.0167). CONCLUSIONS: In comparison with the untreated control group, EP and Seprafilm were found to reduce the formation of intraperitoneal adhesions. No significant difference was found between EP and Seprafilm. PMID- 25126978 TI - A perineal protection device designed to protect the perineum during labor: a multicenter randomized controlled trial. AB - OBJECTIVE: The objective of this study was to evaluate the protective effects of a new device for reducing perineal tears during vaginal childbirth. STUDY DESIGN: A multicenter open randomized controlled trial (RCT) was performed in Helsingborg, Lund and Malmo, Sweden consisting of 1148 women. Women anticipating a vaginal delivery were either randomized to the intervention group (n=574 in which the perineal protection device was used, or a control group (n=574), in which the perineal protection device was not used. The main outcome measurements were incidence of vaginal and perineal tears (1st to 4th degree tears) and adverse effects on the parturient and newborn. RESULTS: The incidences of first- and second-degree tears of the vagina (p=0.018) and perineum (p=0.005) were significantly reduced in the intervention group compared with the controls. In the intervention- and control group, 184 women (34.9%) and 142 (26.6%) showed no perineal tearing, respectively (p=0.034). Numbers needed to treat to avoid any perianal tearing was 12. The incidence of anal sphincter rupture (ASR) was the same in both groups (n=19; 3.4%). No negative effects on mother or child from using the device were observed. CONCLUSIONS: The perineal protective device significantly reduced the incidence of first- and second-degree tears in the vagina and perineum during vaginal birth and also significantly increased the number of parturients with a fully intact posterior commissure. No significant reduction of ASR and no negative effects of the device were observed. PMID- 25126979 TI - Single versus multi-dose antibiotic prophylaxis for pelvic organ prolapse surgery with graft/mesh. AB - OBJECTIVE: To compare the risk of postoperative infections in women who receive single-dose versus multi-dose prophylactic antibiotic regimen during prolapse surgery with mesh/graft. STUDY DESIGN: Retrospective cohort study of 460 women who underwent prolapse surgery with mesh/graft. We compared women who received a single-dose prophylactic antibiotic regimen to those who received a multi-dose regimen. The primary outcome was the presence of any postoperative infection, defined as the presence of any of the following infections: urinary tract infection (UTI), fever, wound or trocar site infection, mesh infection or pelvic abscess. Associations between prophylactic antibiotic regimen and postoperative infections were estimated using univariable and multivariable analysis. RESULTS: Rate of any postoperative infection was similar between the single- and multi dose groups (19% vs. 16%, p=0.50). Rate of UTI was significantly higher in the single-dose compared to the multi-dose group (13% vs. 7%, p=0.03). On multivariable analysis, after controlling for vaginal route of surgery, the odds of UTI was not significantly different between groups (OR 0.59, 95% CI 0.27, 1.26). CONCLUSION: A single-dose antibiotic regimen is sufficient for prophylaxis against postoperative infections in women undergoing prolapse surgery with graft/mesh. PMID- 25126980 TI - Subchorionic hematoma occurs more frequently in in vitro fertilization pregnancy. AB - OBJECTIVE: Obstetric complications occur more frequently in pregnancies after in vitro fertilization (IVF). We attempted to determine the correlation between subchorionic hematoma and IVF pregnancies. STUDY DESIGN: We analyzed 194 pregnancies achieved by infertility treatment between January 2008 and February 2012 at our hospital. Among these, 67 were achieved by IVF and 127 by non-IVF approaches. We compared the frequency of subchorionic hematoma between the groups and examined the risk factors for subchorionic hematoma in the IVF group. RESULTS: No significant differences regarding age and the number of uterine surgery were observed between the groups. The duration of infertility was longer, parity and the rate of luteal support were higher in the IVF group compared with that in the non-IVF group. The frequency of subchorionic hematoma was significantly higher in the IVF group (22.4%) than that in the non-IVF group (11%) (P=0.035). Univariate analysis in the IVF group demonstrated that frozen thawed embryo transfer (OR, 6.18; 95% CI, 1.7-22.4), parity>=1 (OR, 3.67; 95% CI, 1.0-13.2) and blastocyst transfer (OR, 3.75; 95% CI, 1.1-13.3) were risk factors for the subchorionic hematoma. CONCLUSION: The frequency of subchorionic hematoma is high in IVF pregnancies, and frozen-thawed embryo transfer, parity>=1, and blastocyst transfer may contribute to subchorionic hematoma onset. PMID- 25126981 TI - Maternal and neonatal outcomes in women undergoing bariatric surgery: a systematic review and meta-analysis. AB - BACKGROUND: Obese women are at increased risk for many pregnancy complications, and bariatric surgery (BS) before pregnancy has shown to improve some of these. OBJECTIVES: To review the current literature and quantitatively assess the obstetric and neonatal outcomes in pregnant women who have undergone BS. SEARCH STRATEGY: MEDLINE, EMBASE and Cochrane databases were searched using relevant keywords to identify studies that reported on pregnancy outcomes after BS. SELECTION CRITERIA: Pregnancy outcome in firstly, women after BS compared to obese or BMI-matched women with no BS and secondly, women after BS compared to the same or different women before BS. Only observational studies were included. DATA COLLECTION AND ANALYSIS: Two investigators independently collected data on study characteristics and outcome measures of interest. These were analysed using the random effects model. Heterogeneity was assessed and sensitivity analysis was performed to account for publication bias. MAIN RESULTS: The entry criteria were fulfilled by 17 non-randomised cohort or case-control studies, including seven with high methodological quality scores. In the BS group, compared to controls, there was a lower incidence of preeclampsia (OR 0.45, 95% CI 0.25-0.80; P=0.007), GDM (OR 0.47, 95% CI 0.40-0.56; P<0.001) and large neonates (OR 0.46, 95% CI 0.34 0.62; P<0.001) and a higher incidence of small neonates (OR 1.93, 95% CI 1.52 2.44; P<0.001), preterm birth (OR 1.31, 95% CI 1.08-1.58; P=0.006), admission for neonatal intensive care (OR 1.33, 95% CI 1.02-1.72; P=0.03) and maternal anaemia (OR 3.41, 95% CI 1.56-7.44, P=0.002). CONCLUSIONS: BS as a whole improves some pregnancy outcomes. Laparoscopic adjustable gastric banding does not appear to increase the rate of small neonates that was seen with other BS procedures. Obese women of childbearing age undergoing BS need to be aware of these outcomes. PMID- 25126982 TI - Uterine arteriovenous malformations following gestational trophoblastic neoplasia: a systematic review. AB - Uterine arteriovenous malformation (AVM) following gestational trophoblastic neoplasia (GTN) is a rare condition. It can be associated with chronic vaginal bleeding or life-threatening heavy bleeding, even after complete resolution of the tumor following chemotherapy. This analysis aimed to perform an extensive systematic review highlighting clinical symptoms, imaging, management and prognosis of this rare complication of GTN. We also describe an additional case of uterine AVM following GTN. We conducted a literature search using Medline, Embase and Cochrane library to analyze the clinical data of 49 published cases of uterine AVM following GTN. Median age of the women diagnosed with AVM was 29 years (range 15-49). Median gravidity was 2 (range 1-8) and 50% of women were nulligravida. Complete molar pregnancy was the most common initial gestational trophoblastic diagnosis (48%). Overall, 44 patients (88%) were symptomatic and presented with chronic or acute abnormal vaginal bleeding. Only 3 patients had an undetectable HCG level at the time of uterine AVM diagnosis. Hypo-echoic space in the myometrium is the most relevant finding on ultrasonography but the gold standard for the definitive diagnosis of AVMs is angiographic examination. Uterine artery embolization was the most common treatment option performed in 82% of the patients and was successful in controlling the bleeding in 85% of cases. We identified 20 pregnancies after successful embolization of uterine AVM following a GTN and 90% of them were successful. Because of the risk of life threatening heavy bleeding, the diagnosis of uterine AVM should always be considered in patients with a history of recurrent unexplained vaginal bleeding after gestational trophoblastic neoplasia. Angiographic embolization is successful in the majority of cases and does not appear to compromise future pregnancy. PMID- 25126983 TI - [Mediator effect of resilience between burnout and health in nursing staff]. AB - AIMS: To determine the relationships between 3 burnout dimensions (Emotional Exhaustion, Depersonalization, and Reduced Personal Accomplishment), health (physical and mental health), and resilience, as well as to analyse the mediator role of resilience in relationships between burnout and health in a sample of Nursing staff. METHOD: A correlational and cross-sectional study with probabilistic sampling was conducted on a sample of 194 Nursing staff of University Hospital of Fuenlabrada (Madrid), and composed of nurses (n=133) and nursing assistants (n=61). INSTRUMENTS: MBI-HSS (burnout syndrome), SF-12v1 (physical and mental components of health), 10-Item CD-RISC (resilience), and sociodemographic variables. RESULTS: Correlational analyses showed that mental health was negatively related with 3 burnout dimensions and positively with resilience. Furthermore, physical health was only negatively related with Emotional Exhaustion, and positively with resilience. Mediational analyses revealed that resilience mediated, on one hand, the relationship between Emotional Exhaustion and Depersonalization with mental health (partial mediation) and, on the other hand, the relationship between Reduced Personal Accomplishment and mental health (total mediation). CONCLUSIONS: Resilience is not only important to improve the mental health of Nursing staff, but also to buffer and minimize the negative consequences of the occupational stress to which they are at risk, with its most adverse result being signs of burnout. Therefore, resilience training should be promoted to improve nursing clinical practice. PMID- 25126984 TI - Identification of catalytic residues of a very large NAD-glutamate dehydrogenase from Janthinobacterium lividum by site-directed mutagenesis. AB - We previously found a very large NAD-dependent glutamate dehydrogenase with approximately 170 kDa subunit from Janthinobacterium lividum (Jl-GDH) and predicted that GDH reaction occurred in the central domain of the subunit. To gain further insights into the role of the central domain, several single point mutations were introduced. The enzyme activity was completely lost in all single mutants of R784A, K810A, K820A, D885A, and S1142A. Because, in sequence alignment analysis, these residues corresponded to the residues responsible for glutamate binding in well-known small GDH with approximately 50 kDa subunit, very large GDH and well-known small GDH may share the same catalytic mechanism. In addition, we demonstrated that C1141, one of the three cysteine residues in the central domain, was responsible for the inhibition of enzyme activity by HgCl2, and HgCl2 functioned as an activating compound for a C1141T mutant. At low concentrations, moreover, HgCl2 was found to function as an activating compound for a wild-type Jl-GDH. This suggests that the mechanism for the activation is entirely different from that for the inhibition. PMID- 25126985 TI - Identification of newly isolated Talaromyces pinophilus and statistical optimization of beta-glucosidase production under solid-state fermentation. AB - Fungi able to degrade agriculture wastes were isolated from different soil samples, rice straw, and compost; these isolates were screened for their ability to produce beta-glucosidase. The most active fungal isolate was identified as Talaromyces pinophilus strain EMOO 13-3. The Plackett-Burman design is used for identifying the significant variables that influence beta-glucosidase production under solid-state fermentation. Fifteen variables were examined for their significances on the production of beta-glucosidase in 20 experimental runs. Among the variables screened, moisture content, Tween 80, and (NH4)2SO4 had significant effects on beta-glucosidase production with confidence levels above 90% (p < 0.1). The optimal levels of these variables were further optimized using Box-Behnken statical design. As a result, the maximal beta-glucosidase activity is 3648.519 U g(-1), which is achieved at the following fermentation conditions: substrate amount 0.5 (g/250 mL flask), NaNO3 0.5 (%), KH2PO4 0.3 (%), KCl 0.02 (%), MgSO4 . 7H2O 0.01 (%), CaCl2 0.01 (%), yeast extract 0.07 (%), FeSO4 . 7H2O 0.0002 (%), Tween 80 0.02 (%), (NH4)2SO4 0.3 (%), pH 6.5, temperature 25 degrees C, moisture content 1 (mL/g dry substrate), inoculum size 0.5 (mL/g dry substrate), and incubation period 5 days. PMID- 25126986 TI - Activating PI3-kinase to dampen inflammation. AB - Diterpene derivatives of the natural product acanthoic acid have potent anti inflammatory effects in vivo. In this issue of Chemistry & Biolgy, Traves and colleagues report that the primary molecular mechanism of action of diterpenes structurally related to acanthoic acid is the direct activation of PI3-kinase signaling in macrophages, which in turn inhibits NF-kappaB activation and suppresses proinflammatory gene expression. PMID- 25126987 TI - Rehabilitating mutant GCase. AB - Gaucher's disease is a hereditary deficiency of the enzyme beta glucocerebrosidase (GCase) that is most commonly treated by enzyme replacement therapy. In this issue of Chemistry & Biology, Tan and colleagues search for alternative ways to rehabilitate mutant GCase by understanding how it interacts with the proteostasis network. PMID- 25126988 TI - Copper as a magic bullet for targeted microbial killing. AB - The innate toxicity of copper can be exploited as an antimicrobial. In this issue of Chemistry & Biology Festa and colleagues report the use of QBP, a prochelator form of the metal-chelate 8-hydroxyquinolone, which allows for targeted copper dependent microbial killing at sites of infection. PMID- 25126990 TI - Regulation of nonribosomal peptide synthesis: bis-thiomethylation attenuates gliotoxin biosynthesis in Aspergillus fumigatus. AB - Gliotoxin is a redox-active nonribosomal peptide produced by Aspergillus fumigatus. Like many other disulfide-containing epipolythiodioxopiperazines, a bis-thiomethylated form is also produced. In the case of gliotoxin, bisdethiobis(methylthio)gliotoxin (BmGT) is formed for unknown reasons by a cryptic enzyme. Here, we identify the S-adenosylmethionine-dependent gliotoxin bis-thiomethyltransferase (GtmA), which converts dithiogliotoxin to BmGT. This activity, which is induced by exogenous gliotoxin, is only detectable in protein lysates of A. fumigatus deficient in the gliotoxin oxidoreductase, gliT. Thus, GtmA is capable of substrate bis-thiomethylation. Deletion of gtmA completely abrogates BmGT formation and we now propose that the purpose of BmGT formation is primarily to attenuate gliotoxin biosynthesis. Phylogenetic analysis reveals 124 GtmA homologs within the Ascomycota phylum. GtmA is encoded outside the gliotoxin biosynthetic cluster and primarily serves to negatively regulate gliotoxin biosynthesis. This mechanism of postbiosynthetic regulation of nonribosomal peptide synthesis appears to be quite unusual. PMID- 25126991 TI - LDAI-based chemical labeling of intact membrane proteins and its pulse-chase analysis under live cell conditions. AB - The functions of membrane proteins are tightly controlled by the dynamics such as protein trafficking and degradation. We demonstrated that ligand-directed acyl imidazole (LDAI) chemistry is broadly applicable to selective chemical labeling of various types of membrane-bound proteins under live cell conditions without a need for any tag fragments. The LDAI chemistry enabled pulse-chase analysis of these proteins to determine the half-life, as well as their degradation pathways by the imaging, under almost natural cellular conditions. PMID- 25126989 TI - ERdj3 is an endoplasmic reticulum degradation factor for mutant glucocerebrosidase variants linked to Gaucher's disease. AB - Gaucher's disease (GD) is caused by mutations that compromise beta glucocerebrosidase (GCase) folding in the endoplasmic reticulum (ER), leading to excessive degradation instead of trafficking, which results in insufficient lysosomal function. We hypothesized that ER GCase interacting proteins play critical roles in making quality control decisions, i.e., facilitating ER associated degradation (ERAD) instead of folding and trafficking. Utilizing GCase immunoprecipitation followed by mass-spectrometry-based proteomics, we identified endogenous HeLa cell GCase protein interactors, including ERdj3, an ER resident Hsp40 not previously established to interact with GCase. Depleting ERdj3 reduced the rate of mutant GCase degradation in patient-derived fibroblasts, while increasing folding, trafficking, and function by directing GCase to the profolding ER calnexin pathway. Inhibiting ERdj3-mediated mutant GCase degradation while simultaneously enhancing calnexin-associated folding, by way of a diltiazem-mediated increase in ER Ca(2+) levels, yields a synergistic rescue of L444P GCase lysosomal function. Our findings suggest a combination therapeutic strategy for ameliorating GD. PMID- 25126992 TI - Alternative sigma factor RpoN2 is required for flagellar motility and full virulence of Xanthomonas oryzae pv. oryzae. AB - Xanthomonas oryzae pv. oryzae (Xoo), the bacterial blight pathogen of rice, harbors a single polar flagellum for motility. How the flagellar system is regulated and how it is related to bacterial pathogenesis are not well understood. The genomic sequence of Xoo strain PXO99(A) revealed a flagellar regulon containing over 60 contiguous genes. A gene encoding alternative sigma factor 54 (sigma(54)), named as rpoN2, is located in the central region of the regulon. RT-PCR analysis demonstrated rpoN2 was transcribed in an operon with flgRR, and fleQ. Single gene deletion mutants of the rpoN2 operon were generated. The rpoN2 and fleQ mutant lost swimming motility, whereas the flgRR mutant remained motile. Quantitative RT-PCR analysis further demonstrated that expression of regulatory genes fliA and flgM, and structural genes flgG, flhB, and fliC were significantly down-regulated in the rpoN2 and fleQ mutants. These results indicated that RpoN2 and FleQ synergistically controlled flagellar motility by regulating gene expression. Interestingly, the rpoN2 mutant, but not the fleQ mutant was impaired in its virulence on rice. In addition, we showed that the flagellin gene fliC mutant, which was non-motile, was not defective in virulence. Thus, we concluded that flagellar motility might not be essential for Xoo virulence in rice, and RpoN2 probably regulated bacterial virulence through a manner independent of its role in controlling flagellar gene expression. PMID- 25126993 TI - Sodium hexadecyl sulfate as an interfacial substance adjusting the adsorption of a protein on carbon nanotubes. AB - Carbon nanotubes (CNTs) were functionalized with sodium hexadecyl sulfate (SHS). The lysozyme adsorbed on the SHS-CNTs exhibited a higher activity than that immobilized on the nonfunctionalized CNTs. To explain the experimental results and explore the mechanism of lysozyme adsorption, large-scale molecular dynamics simulations have been performed for a four-component system, including lysozyme, SHS, CNTs in explicit water. It has been found that the assembled SHS molecules form a soft layer on the surface of CNTs. The interactions between lysozyme and SHS induce the rearrangement of SHS molecules, forming a saddle-like structure on the CNT surface. The saddle-like structure fits the shape of the lysozyme, and the active-site cleft of the lysozyme is exposed to the water phase. Whereas, for the lysozyme adsorbed on the nonfunctionalized CNT, due to the hydrophobic interactions, the active-site cleft of the enzyme tends to face the wall of the CNT. The results of this work demonstrate that the SHS molecules as the interfacial substance have a function of adjusting the lysozyme with an appropriate orientation, which is favorable for the lysozyme having a higher activity. PMID- 25126994 TI - Synthesis of antifungal vaccines by conjugation of beta-1,2 trimannosides with T cell peptides and covalent anchoring of neoglycopeptide to tetanus toxoid. AB - Selective strategies for the construction of novel three component glycoconjugate vaccines presenting Candida albicans cell wall glycan (beta-1,2 mannoside) and polypeptide fragments on a tetanus toxoid carrier are described. The first of two conjugation strategies employed peptides bearing an N-terminal thiopropionyl residue for conjugation to a trisaccharide equipped with an acrylate linker and a C-terminal S-acetyl thioglycolyl moiety for subsequent linking of neoglycopeptide to bromoacetylated tetanus toxoid. Michael addition of acrylate trisaccharides to peptide thiol under mildly basic conditions gave a mixture of N- and C- terminal glyco-peptide thioethers. An adaptation of this strategy coordinated S-acyl protection with anticipated thioester exchange equilibria. This furnished a single chemically defined fully synthetic neoglycopeptide conjugate that could be anchored to a tetanus toxoid carrier and avoids the introduction of exogenous antigenic groups. The second strategy retained the N-terminal thiopropionyl residue but replaced the C-terminal S-acetate functionality with an azido group that allowed efficient, selective formation of neoglycopeptide thioethers and subsequent conjugation of these with propargylated tetanus toxoid, but introduced potentially antigenic triazole linkages. PMID- 25126995 TI - Human factors/usability barriers to home medical devices among individuals with disabling conditions: in-depth interviews with positive airway pressure device users. AB - BACKGROUND: Evidence suggests that medical equipment often fails to accommodate the needs of individuals with disabling conditions. Few studies have focused on the accessibility of home medical devices such as positive airway pressure (PAP), which is a type of home medical equipment prescribed for long-term therapy. OBJECTIVE: The purpose of this study was to explore in detail the types of difficulties experienced by patients with physical/sensory impairments who use PAP devices, as an initial step in designing a questionnaire to survey users about this topic. METHODS: In this descriptive study, in-depth interviews were conducted with 19 participants (9 patients with physical/sensory impairment and 10 health care providers). Interviews were coded and analyzed for major topics. RESULTS: Participants detailed the numerous ways in which current PAP devices fail to meet the needs of individuals with physical/sensory impairments (e.g., tremor, poor depth perception, paresis), by requiring patients to perform manually difficult tasks, such as inserting PAP parts through small apertures, attaching parts using a twisting motion, and lifting arms overhead to apply PAP headgear. These demands contributed to patients' frustration with and reduced usage of the home medical device. CONCLUSIONS: Our findings suggest that home medical devices such as PAP may not be currently designed to meet the needs of some users with physical/sensory impairments. Additional studies are needed to measure the prevalence and impact of impairment-related barriers on PAP adherence for this common medical equipment. PMID- 25126996 TI - Predictors of loneliness among older women and men in Sweden: A national longitudinal study. AB - OBJECTIVES: Longitudinal research on loneliness in old age has rarely considered loneliness separately for men and women, despite gender differences in life experiences. The objective of this study was to examine the extent to which older women and men (70+) report feelings of loneliness with a focus on: (a) changes in reported loneliness as people age, and (b) which factors predict loneliness. METHOD: Data from the 2004 and 2011 waves of SWEOLD, a longitudinal national survey, was used (n = 587). The prediction of loneliness in 2011 by variables measured in 2004 and 2004-2011 variable change scores was examined in three logistic regression models: total sample, women and men. Variables in the models included: gender, age, education, mobility problems, depression, widowhood and social contacts. RESULTS: Older people moved into and out of frequent loneliness over time, although there was a general increase in loneliness with age. Loneliness at baseline, depression increment and recent widowhood were significant predictors of loneliness in all three multivariable models. Widowhood, depression, mobility problems and mobility reduction predicted loneliness uniquely in the model for women; while low level of social contacts and social contact reduction predicted loneliness uniquely in the model for men. CONCLUSION: This study challenges the notion that feelings of loneliness in old age are stable. It also identifies important gender differences in prevalence and predictors of loneliness. Knowledge about such differences is crucial for the development of effective policy and interventions to combat loneliness in later life. PMID- 25127002 TI - New insights into the role of water in biological function: studying solvated biomolecules using terahertz absorption spectroscopy in conjunction with molecular dynamics simulations. AB - In life science, water is the ubiquitous solvent, sometimes even called the "matrix of life". There is increasing experimental and theoretical evidence that solvation water is not a passive spectator in biomolecular processes. New experimental techniques can quantify how water interacts with biomolecules and, in doing so, differs from "bulk" water. Terahertz (THz) absorption spectroscopy has turned out to be a powerful tool to study (bio)molecular hydration. The main concepts that have been developed in the recent years to describe the underlying solute-induced sub-picosecond dynamics of the hydration shell are discussed herein. Moreover, we highlight recent findings that show the significance of hydrogen bond dynamics for the function of antifreeze proteins and for molecular recognition. In all of these examples, a gradient of water motion toward functional sites of proteins is observed, the so-called "hydration funnel". By means of molecular dynamics simulations, we provide new evidence for a specific water-protein coupling as the cause of the observed dynamical heterogeneity. The efficiency of the coupling at THz frequencies is explained in terms of a two-tier (short- and long-range) solute-solvent interaction. PMID- 25127003 TI - Implications of marijuana legalization for adolescent substance use. AB - Marijuana that is legally available for adults has multiple implications for adolescent substance use. One potential effect that legalization may have is an increase in adolescent use to due increased availability, greater social acceptance, and possibly lower prices. Legalization may also facilitate the introduction of new formulations of marijuana (edible, vaporized) and with potentially higher potencies. It is unknown what adolescent consumption patterns will be if marijuana is widely available and marketed in different forms, or what effects different patterns of adolescent use will have on cognition, the development of marijuana use disorders, school performance, and the development of psychotic illnesses. Also unclear is whether adolescent users will be experiencing higher levels of tetrahydrocannabinol (THC) compared with previous generations of users due to higher potencies. Although previous studies of the effects of adolescent marijuana use provide some guidance for current policy and public health recommendations, many new studies will be needed that answer questions in the context of use within a legal adult environment. Claims that marijuana has medicinal benefits create additional challenges for adolescent prevention efforts, as they contrast with messages of its harmfulness. Prevention and treatment approaches will need to address perceptions of the safety of marijuana, claims of its medicinal use, and consider family-wide effects as older siblings and parents may increasingly openly consume and advocate for marijuana use. Guidance for primary care physicians will be needed regarded screening and counseling. Widespread legalization and acceptance of marijuana implies that as law enforcement approaches for marijuana control decline, public health, medical, and scientific efforts to understand and reduce negative consequences of adolescent marijuana use need to be substantially increased to levels commensurate with those efforts for tobacco and alcohol. PMID- 25127004 TI - Intertemporal cumulative radiative forcing effects of photovoltaic deployments. AB - Current policies accelerating photovoltaics (PV) deployments are motivated by environmental goals, including reducing greenhouse gas (GHG) emissions by displacing electricity generated from fossil-fuels. Existing practice assesses environmental benefits on a net life-cycle basis, where displaced GHG emissions offset those generated during PV production. However, this approach does not consider that the environmental costs of GHG release during production are incurred early, while environmental benefits accrue later. Thus, where policy targets suggest meeting GHG reduction goals established by a certain date, rapid PV deployment may have counterintuitive, albeit temporary, undesired consequences. On a cumulative radiative forcing (CRF) basis, the environmental improvements attributable to PV might be realized much later than is currently understood, particularly when PV manufacturing utilizes GHG-intensive energy sources (e.g., coal), but deployment occurs in areas with less GHG-intensive electricity sources (e.g., hydroelectric). This paper details a dynamic CRF model to examine the intertemporal warming impacts of PV deployments in California and Wyoming. CRF payback times are longer than GHG payback times by 6-12 years in California and 6-11 years in Wyoming depending on the PV technology mix and deployment strategy. For the same PV capacity being deployed, early installations yield greater CRF benefits (calculated over 10 and 25 years) than installations occurring later in time. Further, CRF benefits are maximized when PV technologies with the lowest manufacturing GHG footprint (cadmium telluride) are deployed in locations with the most GHG-intensive grids (i.e., Wyoming). PMID- 25127005 TI - Using ROC to examine the association between attendance and compliance. PMID- 25127006 TI - Fabrication of boron nitride nanotube-gold nanoparticle hybrids using pulsed plasma in liquid. AB - Plasma, generated in liquid at atmospheric pressure by a nanosecond pulsed voltage, was used to fabricate hybrid structures from boron nitride nanotubes and gold nanoparticles in deionized water. The pH was greatly reduced, conductivity was significantly increased, and concentrations of reactive oxygen and nitrogen species in the water were increased by the plasma treatment. The treatment reduced the length of the nanotubes, giving more individual cuplike structures, and introduced functional groups onto the surface. Gold nanoparticles were successively assembled onto the functionalized surfaces. The reactive species from the liquid plasma along with the nanosecond pulsed electric field seem to play a role in the shortening and functionalization of the nanotubes and the assembly of gold nanoparticles. The potential for targeted drug delivery was tested in a preliminary investigation using doxorubicin-loaded plasma-treated nanotubes which were effective at killing ~99% of prostate cancer cells. PMID- 25127007 TI - Growth and anaerobic digestion characteristics of microalgae cultivated using various types of sewage. AB - Microalgal cultivation combined with anaerobic digestion at wastewater treatment plants is promising to recover energy. This study investigated the growth and anaerobic digestion characteristics of microalgae cultivated using nutrients in sewage. Microalgae were cultivated using primary effluent, secondary effluent, and dewatering filtrate. Microscopic observation indicated that Chlorella was cultivated using dewatering filtrate of anaerobic digestion without controlling the type of species. Batch anaerobic digestion experiments with digested sludge showed that the methane conversion ratio of the cultivated mixture was approximately 40-65%. Different cultivation time did not affect the microalgal contents. Methane recovery mass was 0.13NL-methane/L-cultivation liquor. The C/N ratio of the cultivated mixture was approximately 3-5, but the apparent ammonia release ratio was smaller than that of sewage sludge during digestion. These results proved the applicability of methane recovery from microalgae cultivated using nutrients included in anaerobically digested sludge. PMID- 25127008 TI - Performance of the lysozyme for promoting the waste activated sludge biodegradability. AB - The fresh waste activated sludge (WAS) from a lab-scale sequencing batch reactor was used to determine the performance of the lysozyme for promoting its biodegradability. The results showed that a strict linear relationship presented between the degree of disintegration (DDM) of WAS and the lysozyme incubation time from 0 to 240min (R(2) was 0.992, 0.995 and 0.999 in accordance with the corresponding lysozyme/TS, respectively). Ratio of net SCOD increase augmented significantly by lysozyme digestion for evaluating the sludge biodegradability changes. Moreover, the protein dominated both in the EPS and SMP. In addition, the logarithm of SMP contents in supernatant presented an increasing trend similar with the ascending logarithmic relation with the lysozyme incubation time from 0 to 240min (R(2) was 0.960, 0.959 and 0.947, respectively). The SMP, especially the soluble protein, had an important contribution to the improvement of WAS biodegradability. PMID- 25127009 TI - Enhanced succinic acid production and magnesium utilization by overexpression of magnesium transporter mgtA in Escherichia coli mutant. AB - In this study, a novel engineered Escherichia coli strain KMG111 was constructed by overexpression of mgtA in E. coli mutant DC1515. By adopting KMG111, nearly a concentration of succinic acid (32.41gL(-1)) with a yield of 0.81gg(-1) glucose, could be obtained in a batch fermentation by using the low-cost mixture of Mg(OH)2 and NH3.H2O to replace MgCO3 as the alkaline neutralizer. Moreover, the effect of the inhibitory compounds in lignocellulosic hydrolyzates on cell growth and succinic acid production could be relieved. In a 3-L bioreactor, the overall productivity and yield of succinic acid in the whole anaerobic stage were 2.15gL( 1)h(-1) and 0.86gg(-1) total sugar, respectively. This study was the first to report decreased alkaline neutralizer cost via genetic manipulation for succinic acid production, which contributed to the industrialization of this microbial synthesis process. PMID- 25127010 TI - Upgrading the rice husk char obtained by flash pyrolysis for the production of amorphous silica and high quality activated carbon. AB - The overall valorization of rice husk char obtained by flash pyrolysis in a conical spouted bed reactor (CSBR) has been studied in a two-step process. Thus, silica has been recovered in a first step and the remaining carbon material has been subjected to steam activation. The char samples used in this study have been obtained by continuous flash pyrolysis in a conical spouted bed reactor at 500 degrees C. Extraction with Na2CO3 allows recovering 88% of the silica contained in the rice husk char. Activation of the silica-free rice husk char has been carried out in a fixed bed reactor at 800 degrees C using steam as activating agent. The porous structure of the activated carbons produced includes a combination of micropores and mesopores, with a BET surface area of up to 1365m(2)g(-1) at the end of 15min. PMID- 25127012 TI - Serum adipocyte fatty acid binding protein levels are positively associated with subclinical atherosclerosis in Chinese pre- and postmenopausal women with normal glucose tolerance. AB - CONTEXT: Recent studies highlight a critical interaction between adipocyte fatty acid binding protein (A-FABP) and cardiovascular disorders. However, associations of A-FABP with subclinical atherosclerosis in a population with normal glucose tolerance remain unknown. OBJECTIVE: The study aimed to evaluate the relationship between A-FABP and carotid intima-media thickness (C-IMT) in a Chinese population with normal glucose tolerance. DESIGN AND SETTING: A cross-sectional analysis was conducted of 2253 cardiovascular disease-free normal glucose tolerance subjects (835 men, 1418 women; 20-78 years old) from the Shanghai Obesity Study. MAIN OUTCOME AND MEASURES: C-IMT was measured by B-mode ultrasound and used to assess subclinical atherosclerosis. Serum A-FABP levels were quantified by a sandwich ELISA. RESULTS: The median serum level for A-FABP was 4.0 ng/mL (interquartile range: 2.6-6.0 ng/mL), and significantly higher in women than men (P < .001). After adjusting for age and body mass index (BMI), a partial correlation analysis showed that A-FABP levels correlated with C-IMT in men, premenopausal, and postmenopausal women (P = .024, .006, and .016, respectively). Furthermore, C-IMT increased along with quartile A-FABP values (all P for trend <.001). Regression analyses demonstrated that A-FABP was associated with C-IMT only in women (P = .044 and .001 for pre- and postmenopausal, respectively). Moreover, A-FABP was identified as a risk factor for C-IMT in pre- and postmenopausal women with a normal BMI (P < .001 and P = .012, respectively). CONCLUSIONS: Serum A-FABP levels independently and positively correlate with subclinical atherosclerosis in pre- and postmenopausal Chinese women with normal glucose tolerance after adjustments for the traditional risk factors. PMID- 25127011 TI - A model of BMD changes after alendronate discontinuation to guide postalendronate BMD monitoring. AB - CONTEXT: Women stopping alendronate are commonly monitored with serial bone mineral density (BMD) measurements, yet no information exists on how frequently or for whom these measurements should be performed. OBJECTIVE: The objective of the study was to develop a tool to guide post-alendronate BMD monitoring. DESIGN: A predictive model was constructed to estimate the time until a given percentage of women's BMD T-scores drop below a given threshold that indicates a management change (such as retreatment) would be considered. This model was then used to estimate the time it would take for groups of women defined by their baseline BMDs to drop below the given threshold. SETTING: Data were derived from the Fracture Intervention Trial Long Term Extension (FLEX), the largest multicenter clinical trial of its type to date. PARTICIPANTS: Four hundred four women who had received an average of 5.1 years of alendronate during the Fracture Intervention Trial and were subsequently observed for 5 treatment-free years (on placebo) during the FLEX trial were used to estimate the change in BMD over time. RESULTS: If a management change such as alendronate reinitiation would be considered when BMD T-score drops below -2.5, the model shows that women with total hip BMD greater than -1.9 T-scores at the time of alendronate discontinuation have less than a 20% probability that at follow-up, monitoring BMD will be below the threshold within 5 years. The model performed similarly, and results are provided over a range of management change thresholds from -1.75 to -3 T-scores. CONCLUSIONS: Using the tool developed in this analysis, it is possible to estimate when BMD repeat measurement after alendronate discontinuation could potentially be useful. Measuring BMD within 5 years after alendronate discontinuation is unlikely to change management for women with total hip BMD 0.6 T-scores above a prespecified retreatment threshold within the range of -1.75 to 3 T-scores. PMID- 25127014 TI - A dynamic duo: pairing click chemistry and postpolymerization modification to design complex surfaces. AB - Advances in key 21st century technologies such as biosensors, biomedical implants, and organic light-emitting diodes rely heavily on our ability to imagine, design, and understand spatially complex interfaces. Polymer-based thin films provide many advantages in this regard, but the direct synthesis of polymers with incompatible functional groups is extremely difficult. Using postpolymerization modification in conjunction with click chemistry can circumvent this limitation and result in multicomponent surfaces that are otherwise unattainable. The two methods used to form polymer thin films include physisorption and chemisorption. Physisorbed polymers suffer from instability because of the weak intermolecular forces between the film and the substrate, which can lead to dewetting, delamination, desorption, or displacement. Covalent immobilization of polymers to surfaces through either a "grafting to" or "grafting from" approach provides thin films that are more robust and less prone to degradation. The grafting to technique consists of adsorbing a polymer containing at least one reactive group along the backbone to form a covalent bond with a complementary surface functionality. Grafting from involves polymerization directly from the surface, in which the polymer chains deviate from their native conformation in solution and stretch away from the surface because of the high density of chains. Postpolymerization modification (PPM) is a strategy used by our groups over the past several years to immobilize two or more different chemical functionalities onto substrates that contain covalently grafted polymer films. PPM exploits monomers with reactive pendant groups that are stable under the polymerization conditions but are readily modified via covalent attachment of the desired functionality. "Click-like" reactions are the most common type of reactions used for PPM because they are orthogonal, high-yielding, and rapid. Some of these reactions include thiol-based additions, activated ester coupling, azide-alkyne cycloadditions, some Diels-Alder reactions, and non-aldol carbonyl chemistry such as oxime, hydrazone, and amide formation. In this Account, we highlight our research combining PPM and click chemistry to generate complexity in polymer thin films. For the purpose of this Account, we define a complex coating as a polymer film grafted to a planar surface that acts as a template for the patterning of two or more discrete chemical functionalities using PPM. After a brief introduction to grafting, the rest of the review is arranged in terms of the sequence in which PPM is performed. First, we describe sequential functionalization using iterations of the same click-type reaction. Next, we discuss the use of two or more different click-like reactions performed consecutively, and we conclude with examples of self-sorting reactions involving orthogonal chemistries used for one-pot surface patterning. PMID- 25127013 TI - Association between anticoagulant treatment duration and risk of venous thromboembolism recurrence and bleeding in clinical practice. AB - INTRODUCTION: This retrospective observational study examined whether anticoagulant treatment duration varies by risks of venous thromboembolism (VTE) recurrence and bleeding. MATERIALS AND METHODS: VTE patients naive to anticoagulants were identified from the HealthCore Integrated Research Database between 06/01/2007 and 09/30/2011 and categorized into three groups: provoked, cancer-related, and unprovoked VTE. Treatment duration was from initiation to discontinuation of anticoagulation, based on a 60-day gap in prescription fill unless there was an international normalized ratio test every 42 days. Bleeding risk was estimated using RIETE score, and VTE risk categories were based on ACCP guidelines. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate association between VTE recurrence/bleeding and anticoagulation duration. RESULTS: Of 2002 patients identified (52.3% males, mean age 57 +/-15 years), 21.4% had provoked, 16.4% had cancer-related, and 62.1% had unprovoked VTE. Average anticoagulant treatment duration was 294 +/- 261 days. After adjusting for demographics and clinical characteristics, provoked and cancer related VTE patients were 32% (95% CI=14-54%, P<0.001) and 35% (95% CI=7-70%, P=0.013) more likely, respectively, to discontinue anticoagulants than unprovoked VTE patients. No differences were observed between provoked and cancer-related VTE patients. Patients with an intermediate/high bleeding risk were 26% (95% CI=14-36%, P<0.001) less likely to discontinue treatment than those with a low bleeding risk. CONCLUSIONS: The observed anticoagulation duration for VTE may not be concordant with guidelines, due to the challenge of counterbalancing risks of VTE recurrence and bleeding. Further studies are needed to explore this. PMID- 25127015 TI - Is the exoproteome important for bacterial pathogenesis? Lessons learned from interstrain exoprotein diversity in Listeria monocytogenes grown at different temperatures. AB - Bacterial exoproteomes vary in composition and quantity among species and within each species, depending on the environmental conditions to which the cells are exposed. This article critically reviews the literature available on exoproteins synthesized by the foodborne pathogenic bacterium Listeria monocytogenes grown at different temperatures. The main challenges posed for exoproteome analyses and the strategies that are being used to overcome these constraints are discussed. Over thirty exoproteins from L. monocytogenes are considered, and the multifunctionality of some of them is discussed. Thus, at the host temperature of 37 degrees C, good examples are provided by Lmo0443, a potential marker for low virulence, and by the virulence factors internalin C (InlC) and listeriolysin O (LLO). Based on the reported LLO-induced mucin exocytosis, a model is proposed for the involvement of extracellular LLO in optimizing the conditions for InlC intervention in the invasion of intestinal epithelial cells. At lower growth temperatures, exoproteins such as flagellin (FlaA) and oligopeptide permease (OppA) may explain the persistence of particular strains in the food industry environment, eventually allowing the development of new tools to eradicate L. monocytogenes, a major concern for public health. PMID- 25127016 TI - Regulation of lipid metabolism in the green microalga Chlorella protothecoides by heterotrophy-photoinduction cultivation regime. AB - Proteomics in conjunction with biochemical strategy was employed to unravel regulation of lipid metabolism in the green microalga Chlorella protothecoides by heterotrophy-photoinduction cultivation regime (HPC). Interestingly, HPC triggered transiently synthesis of starch followed by substantial lipid accumulation. And a marked decrease in intracellular protein and chlorophyll contents was also observed after 12h of photo-induction. The highest lipid content of 50.5% was achieved upon the photo-induction stage, which represented 69.3% higher than that of the end of heterotrophic cultivation. Results suggested that turnover of carbon-nitrogen-rich compounds such as starch, protein, and chlorophyll might provide carbon or energy for lipid accumulation. The proteomics analysis indicated that several pathways including glycolysis, TCA cycle, beta oxidation of fatty acids, Calvin cycle, photosynthesis, energy and transport, protein biosynthesis, regulate and defense were involved in the lipid biosynthesis. Malate dehydrogenase and acyl-CoA dehydrogenase were suggested as key regulatory factors in enhancing lipid accumulation. PMID- 25127018 TI - Copper-catalyzed direct alkylation of 1,3-azoles with N-tosylhydrazones bearing a ferrocenyl group: a novel method for the synthesis of ferrocenyl-based ligands. AB - Copper-catalyzed cross-coupling of ferrocenyl ketone-derived N-tosylhydrazones with benzo[d]oxazole leads to the direct C-H bond functionalization by a secondary ferrocenyl alkyl group. This direct C-H bond alkylation of azoles with N-tosylhydrazones bearing a ferrocenyl group uses inexpensive CuBr as the catalyst without any ligand. The reaction is operationally simple and conducted under mild conditions, giving the corresponding ferrocenyl-based ligands in moderate to good yields. Furthermore, they were able to act as bidentate ligands, giving rise to the corresponding palladium chelated complex 6a-6c, which were obtained by reaction of 5a-5c with [PdCl2(MeCN)2]. PMID- 25127017 TI - HIV-1 replication in human immune cells is independent of TAR DNA binding protein 43 (TDP-43) expression. AB - The TAR DNA binding protein (TDP-43) was originally identified as a host cell factor binding to the HIV-1 LTR and thereby suppressing HIV-1 transcription and gene expression (Ou et al., J.Virol. 1995, 69(6):3584). TDP-43 is a global regulator of transcription, can influence RNA metabolism in many different ways and is ubiquitously expressed. Thus, TDP-43 could be a major factor restricting HIV-1 replication at the level of LTR transcription and gene expression. These facts prompted us to revisit the role of TDP-43 for HIV-1 replication. We utilized established HIV-1 cell culture systems as well as primary cell models and performed a comprehensive analysis of TDP-43 function and investigated its putative impact on HIV-1 gene expression. In HIV-1 infected cells TDP-43 was neither degraded nor sequestered from the nucleus. Furthermore, TDP-43 overexpression as well as siRNA mediated knockdown did not affect HIV-1 gene expression and virus production in T cells and macrophages. In summary, our experiments argue against a restricting role of TDP-43 during HIV-1 replication in immune cells. PMID- 25127019 TI - Meroterpenes from Psoralea corylifolia against Pyricularia oryzae. AB - Six new meroterpenes, namely, 13-methoxyisobakuchiol (1), 13-ethoxyisobakuchiol (2), 12,13-dihydro-13-hydroxybakuchiol (3), Delta(10)-12,13-dihydro-12-(R,S) methoxyisobakuchiol (4 and 5), and 15-demetyl-12,13-dihydro-13-ketobakuchiol (6), together with four known ones, namely, Delta(3),2-hydroxybakuchiol (7), Delta(1),3-hydroxybakuchiol (8), bakuchiol (9), and Delta(1,3)-bakuchiol (10), were isolated from the seeds of Psoralea corylifolia. Their structures were identified based on spectral data, including those obtained via 1D and 2D NMR, and MS spectral analyses. Antifungal screening results indicated that all compounds showed moderate inhibitory activities against Pyricularia oryzae. PMID- 25127020 TI - Antihyperlipidemic effects of rhapontin and rhapontigenin from rheum undulatum in rats fed a high-cholesterol diet. AB - Rhapontin was purified from a methanol extract from the roots of Rheum undulatum, and rhapontigenin was produced by an enzymatic transformation of rhapontin. Rats were fed a high-cholesterol diet to induce hyperlipidemia, followed by oral treatment with rhapontin or rhapontigenin (1-5 mg/kg/day). Rhapontin and rhapontigenin treatment resulted in a significant (p<0.05) dose-dependent decrease in the serum lipid level, while the high-density lipoprotein cholesterol level increased slightly compared with the experimental control. Furthermore, rhapontin and rhapontigenin treatment improved the pathological characteristics of the degenerating fatty liver in high-cholesterol diet-induced hyperlipidemic rats dose-dependently. Aspartate aminotransferase and alanine aminotransferase levels in rhapontin- and rhapontigenin-treated hyperlipidemic rats were not significantly different from those in the control. These results indicate that rhapontin and rhapontigenin can be used as potent antihyperlipidemic agents. PMID- 25127021 TI - Amide alkaloids from Scopolia tangutica. AB - Four new hydroxycinnamic acid amides, scotanamines A-D (1-4), and seven known alkaloids, including N (1),N (10)-di-dihydrocaffeoylspermidine (5), scopolamine (6), anisodamine (7), hyoscyamine (8), anisodine (9), caffeoylputrescine (10), and N (1)-caffeoyl-N (3)-dihydrocaffeoylspermidine (11), were obtained from the roots of Scopolia tangutica. The present study represents the first recognition of hydroxycinnamic acid amides containing putrescine or spermidine in S. tangutica. Compound 1, in particular, contains a moiety resulting from the condensation of nortropinone and putrescine. Compound 2 exhibited moderate agonist activity at the u-opioid receptor (EC50=7.3 uM). Compound 2 was tested in vivo and induced analgesia in mice. The analgesic effect was recorded using the tail-flick assay and was reversed by naloxone. PMID- 25127022 TI - Isolation, characterization, and antitumor activity of a novel heteroglycan from cultured mycelia of Cordyceps sinensis. AB - A novel heteroglycan, Cordyceps sinensis polysaccharide 1 (molecular weight 1 17 * 10(5) Da), was isolated and purified from mycelia of the fungus C. sinensis obtained by solid-state culture. Structural characterization by chemical analysis, GC-MS, FTIR, and NMR spectroscopy showed that C. sinensis polysaccharide 1 was mainly composed of (1 -> 6)-linked alpha-D-Glc and alpha-D Gal, with minor beta-(1 -> 4)-D-Xyl and beta-(1 -> 4)-D-Man residues probably located in the side chains with a trace amount of alpha-(1 -> 3)-L-Rha residue. In biological assays, C. sinensis polysaccharide 1 significantly inhibited proliferation of sarcoma 180 cells and induced apoptosis in a dose-dependent manner. Further studies will elucidate the antitumor mechanism of C. sinensis polysaccharide 1 and promote its utilization for the development of novel, effective anticancer drugs. PMID- 25127024 TI - Fumigaclavines D-H, new ergot alkaloids from endophytic Aspergillus fumigatus. AB - Ergot alkaloids are toxins which are produced biotechnologically on an industrial scale. The chemical investigation of endophytic Aspergillus fumigatus resulted in the isolation of five new ergot alkaloids named fumigaclavines D-H (2-6), along with three known analogues, fumigaclavine C (1), festuclavine (7), and fumigaclavine A (8). Their structures were unequivocally elucidated by extensive spectroscopic analyses in association with X-ray single-crystal diffraction. Fumigaclavines D-H are interesting clavine-type ergot alkaloids featuring a reverse prenyl moiety at C-2, with 1-4, 6, and 8 bearing additional substituents, e.g., an OH or OAc group at C-9. Compounds 2, 4, and 6-8 showed a broad spectrum of antimicrobial activity against a panel of anaerobic microorganisms, of which compounds 4 and 6 were the most active against Veillonella parvula with an MIC=16 ug/mL compared to that (0.12 ug/mL) of tinidazole, co-assayed as a positive reference. PMID- 25127023 TI - Chemical composition and biological effects of Artemisia maritima and Artemisia nilagirica essential oils from wild plants of western Himalaya. AB - Artemisia species possess pharmacological properties that are used for medical purposes worldwide. In this paper, the essential oils from the aerial parts of Artemisia nilagirica and Artemisia maritima from the western Indian Himalaya region are described. The main compounds analyzed by simultaneous GC/MS and GC/FID were camphor and 1,8-cineole from A. maritima, and camphor and artemisia ketone from A. nilagirica. Additionally, the oils were evaluated for their antibacterial, antifungal, mosquito biting deterrent, and larvicidal activities. A. nilagirica essential oil demonstrated nonselective antifungal activity against plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides, whereas A. maritima did not show antifungal activity. Both Artemisia spp. exhibited considerable mosquito biting deterrence, whereas only A. nilagirica showed larvicidal activity against Aedes aegypti. Antibacterial effects assessed by an agar dilution assay demonstrated greater activity of A. maritima essential oil against Staphylococcus aureus and Pseudomonas aeruginosa compared to A. nilagirica. PMID- 25127025 TI - Effective treatment of invasive Aspergillus fumigatus infection using combinations of topical and systemic antifungals in a severely burned patient. AB - The authors describe an invasive Aspergillus fumigatus deep-burn wound infection in a severely burned patient that was successfully treated with a combination of topical terbinafine and systemic voriconazole antifungal therapy. To our knowledge, this is the first case report describing the effective control of an invasive deep-burn wound infection using this combination. PMID- 25127026 TI - The effects of intravenous vitamin C on point-of-care glucose monitoring. AB - Ascorbic acid (vitamin C) decreases systemic inflammation and lowers fluid requirements after thermal injury; therefore it has been adopted in many burn centers as an adjunct to resuscitation. However, recent concerns have been expressed over clinically significant hypoglycemic events caused by vitamin C interference with the point-of-care (POC) glucose measurements. This case series presents a direct comparison of POC and laboratory reference glucose values in the patients receiving vitamin C infusion. Vitamin C was administered at 66 mg/kg/hour in seven patients with burns >30% TBSA. The baseline characteristics and burn characteristics were recorded. POC glucose measurements were made with a commonly used hand-held device, and the laboratory values were obtained using standard spectrophotometric methods. POC and laboratory glucose values drawn within the same hour were compared. Hemoglobin, which is known to cause interference in POC testing, was also recorded. All the patients demonstrated falsely elevated POC glucose values during and/or immediately after the infusion period, with discrepancies ranging from 10 to 200 mg/dl. These findings were irregular, unpredictable and unrelated to hemoglobin levels. The findings suggest an idiosyncratic reaction that cannot be easily corrected at the bedside using mathematical equations. POC glucose monitoring should be avoided during and after vitamin C therapy. PMID- 25127028 TI - Delirium screening anchored in child development: The Cornell Assessment for Pediatric Delirium. AB - OBJECTIVE: The recently validated Cornell Assessment for Pediatric Delirium (CAPD) is a new rapid bedside nursing screen for delirium in hospitalized children of all ages. The present manuscript provides a "developmental anchor points" reference chart, which helps ground clinicians' assessment of CAPD symptom domains in a developmental understanding of the presentation of delirium. METHOD: During the development of this CAPD screening tool, it became clear that clinicians need specific guidance and training to help them draw on their expertise in child development and pediatrics to improve the interpretative reliability of the tool and its accuracy in diagnosing delirium. The developmental anchor points chart was formulated and reviewed by a multidisciplinary panel of experts to evaluate content validity and include consideration of sick behaviors within a hospital setting. RESULTS: The CAPD developmental anchor points for the key ages of newborn, 4 weeks, 6 weeks, 8 weeks, 28 weeks, 1 year, and 2 years served as the basis for training bedside nurses in scoring the CAPD for the validation trial and as a multifaceted bedside reference chart to be implemented within a clinical setting. In the current paper, we discuss the lessons learned during implementation, with particular emphasis on the importance of collaboration with the bedside nurse, the challenges of establishing a developmental baseline, and further questions about delirium diagnosis in children. SIGNIFICANCE OF RESULTS: The CAPD with developmental anchor points provides a validated, structured, and developmentally informed approach to screening and assessment of delirium in children. With minimal training on the use of the tool, bedside nurses and other pediatric practitioners can reliably identify children at risk for delirium. PMID- 25127027 TI - Loss of Intralipid(r)- but not sevoflurane-mediated cardioprotection in early type-2 diabetic hearts of fructose-fed rats: importance of ROS signaling. AB - BACKGROUND: Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid(r) and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury. METHODS: Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid(r) (1%) was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-%) served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained. RESULTS: Intralipid(r) did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid(r) produced protective ROS during reperfusion, which activated Akt. Intralipid(r) failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3. CONCLUSIONS: Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid(r) potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection. PMID- 25127030 TI - Catheter ablation for atrial fibrillation after an unsuccessful surgical ablation and biological prosthetic mitral valve replacement: a pilot study. AB - BACKGROUND: Patients with mitral valve (MV) disease and atrial fibrillation (AF) undergo simultaneous prosthetic valve replacement and radiofrequency (RF) ablation procedure; however, this combinational procedure restores sinus rhythm (SR) in only 68-82% of the cases. In patients with ineffective surgical ablation, the use of a biological prosthetic valve might not only be a good choice to perform safe catheter ablation procedure in the left atrium (LA), but also provide a way to discontinue administration of oral anticoagulants. The objective of this study was to assess the efficacy of catheter ablation for AF after MV replacement with a biological prosthesis and an ineffective surgical ablation procedure. METHODS: Ten consecutive patients aged 48 +/- 7 years were enrolled in this study. All patients had long-persistent AF associated with a rheumatic valve disease, which was treated by MV replacement with a biological prosthesis and a surgical RF ablation procedure. In the late postoperative period, all the patients had recurrent hemodynamically significant AF, which required repeated cardioversions. From 1 year to 3 years after the surgery, catheter ablation was performed, including reisolation of pulmonary veins (PVs) with the ablation of ganglionic plexi or linear lesions on the roof of the LA and mitral isthmus. The efficacy was assessed at 3 months, 6 months, and 12 months after the procedure. RESULTS: Restoration of SR during ablation was achieved in all of the cases. In 6 9 months, all the patients were free of arrhythmia. LA stunning manifested by the absence or decrease of the "A" wave in the transmitral flow and the retrograde wave in the PV flow was observed in nine patients with SR. In five of the patients, LA contractile function was restored in 1-6 months. Prosthetic valve dysfunction was not detected in any of the patients. CONCLUSION: Catheter ablation is an effective method for AF treatment following an ineffective surgical RF ablation procedure and biological prosthetic MV replacement. The use of bioprosthetic MVs allows for performing safe catheter ablation without subsequent prosthetic dysfunction. PMID- 25127029 TI - Increased expression of chemerin in squamous esophageal cancer myofibroblasts and role in recruitment of mesenchymal stromal cells. AB - Stromal cells such as myofibroblasts influence tumor progression. The mechanisms are unclear but may involve effects on both tumor cells and recruitment of bone marrow-derived mesenchymal stromal cells (MSCs) which then colonize tumors. Using iTRAQ and LC-MS/MS we identified the adipokine, chemerin, as overexpressed in esophageal squamous cancer associated myofibroblasts (CAMs) compared with adjacent tissue myofibroblasts (ATMs). The chemerin receptor, ChemR23, is expressed by MSCs. Conditioned media (CM) from CAMs significantly increased MSC cell migration compared to ATM-CM; the action of CAM-CM was significantly reduced by chemerin-neutralising antibody, pretreatment of CAMs with chemerin siRNA, pretreatment of MSCs with ChemR23 siRNA, and by a ChemR23 receptor antagonist, CCX832. Stimulation of MSCs by chemerin increased phosphorylation of p42/44, p38 and JNK-II kinases and inhibitors of these kinases and PKC reversed chemerin stimulated MSC migration. Chemerin stimulation of MSCs also induced expression and secretion of macrophage inhibitory factor (MIF) that tended to restrict migratory responses to low concentrations of chemerin but not higher concentrations. In a xenograft model consisting of OE21 esophageal cancer cells and CAMs, homing of MSCs administered i.v. was inhibited by CCX832. Thus, chemerin secreted from esophageal cancer myofibroblasts is a potential chemoattractant for MSCs and its inhibition may delay tumor progression. PMID- 25127032 TI - Glioma-derived ADAM10 induces regulatory B cells to suppress CD8+ T cells. AB - CD8+ T cells play an important role in the anti-tumor activities of the body. The dysfunction of CD8+ T cells in glioma is unclear. This study aims to elucidate the glioma cell-derived ADAM10 (A Disintegrin and metalloproteinase domain containing protein 10) in the suppression of CD8+ effector T cells by the induction of regulatory B cells. In this study, glioma cells were isolated from surgically removed glioma tissue and stimulated by Phorbol myristate acetage (PMA) in the culture. The levels of ADAM10 in the culture were determined by enzyme-linked immunosorbent assay. Immune cells were assessed by flow cytometry. The results showed that the isolated glioma cells express ADAM10, which was markedly up regulated after stimulated with PMA. The glioma-derived ADAM10 induced activated B cells to differentiate into regulatory B cells, the later suppressed CD8+ T cell proliferation as well as the induced regulatory T cells, which also showed the immune suppressor effect on CD8+ effector T cell proliferation. In conclusion, glioma cells produce ADAM10 to induce Bregs; the latter suppresses CD8+ T cells and induces Tregs. PMID- 25127031 TI - Sequestering HMGB1 via DNA-conjugated beads ameliorates murine colitis. AB - Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract that affects millions of people worldwide. Although the etiology of IBD is not clear, it is known that products from stressed cells and enteric microbes promote intestinal inflammation. High mobility group box 1 (HMGB1), originally identified as a nuclear DNA binding protein, is a cytokine-like protein mediator implicated in infection, sterile injury, autoimmune disease, and IBD. Elevated levels of HMGB1 have been detected in inflamed human intestinal tissues and in feces of IBD patients and mouse models of colitis. Neutralizing HMGB1 activity by administration of anti-HMGB1 antibodies or HMGB1-specific antagonist improves clinical outcomes in animal models of colitis. Since HMGB1 binds to DNA with high affinity, here we developed a novel strategy to sequester HMGB1 using DNA immobilized on sepharose beads. Screening of DNA-bead constructs revealed that B2 beads, one linear form of DNA conjugated beads, bind HMGB1 with high affinity, capture HMGB1 ex vivo from endotoxin-stimulated RAW 264.7 cell supernatant and from feces of mice with colitis. Oral administration of B2 DNA beads significantly improved body weight, reduced colon injury, and suppressed colonic and circulating cytokine levels in mice with spontaneous colitis (IL-10 knockout) and with dextran sulfate sodium-induced colitis. Thus, DNA beads reduce inflammation by sequestering HMGB1 and may have therapeutic potential for the treatment of IBD. PMID- 25127034 TI - Estrogen receptor-alpha36 is involved in pterostilbene-induced apoptosis and anti proliferation in in vitro and in vivo breast cancer. AB - Pterostilbene (trans-3,5-dimethoxy-4'-hudroxystilbene) is an antioxidant primarily found in blueberries. It also inhibits breast cancer regardless of conventional estrogen receptor (ER-alpha66) status by inducing both caspase dependent and caspase-independent apoptosis. However, the pterostilbene-induced apoptosis rate in ER-alpha66-negative breast cancer cells is much higher than that in ER-alpha66-positive breast cancer cells. ER-alpha36, a variant of ER alpha66, is widely expressed in ER-alpha66-negative breast cancer, and its high expression mediates the resistance of ER-alpha66-positive breast cancer patients to tamoxifen therapy. The aim of the present study is to determine the relationship between the antiproliferation activity of pterostilbene and ER alpha36 expression in breast cancer cells. Methyl-thiazolyl-tetrazolium (MTT) assay, apoptosis analysis, and an orthotropic xenograft mouse model were used to examine the effects of pterostilbene on breast cancer cells. The expressions of ER-alpha36 and caspase 3, the activation of ERK and Akt were also studied through RT-PCR, western blot analysis, and immunohistochemical (IHC) staining. ER-alpha36 knockdown was found to desensitize ER-alpha66-negative breast cancer cells to pterostilbene treatment both in vitro and in vivo, and high ER-alpha36 expression promotes pterostilbene-induced apoptosis in breast cancer cells. Western blot analysis data indicate that MAPK/ERK and PI3K/Akt signaling in breast cancer cells with high ER-alpha36 expression are mediated by ER-alpha36, and are inhibited by pterostilbene. These results suggest that ER-alpha36 is a therapeutic target in ER-alpha36-positive breast cancer, and pterostilbene is an inhibitor that targets ER-alpha36 in the personalized therapy against ER-alpha36 positive breast cancer. PMID- 25127035 TI - Response of various conduit arteries in tachycardia- and volume overload-induced heart failure. AB - Although hemodynamics changes occur in heart failure (HF) and generally influence vascular function, it is not clear whether various HF models will affect the conduit vessels differentially or whether local hemodynamic forces or systemic factors are more important determinants of vascular response in HF. Here, we studied the hemodynamic changes in tachycardia or volume-overload HF swine model (created by either high rate pacing or distal abdominal aortic-vena cava fistula, respectively) on carotid, femoral, and renal arteries function and molecular expression. The ejection fraction was reduced by 50% or 30% in tachycardia or volume-overload model in four weeks, respectively. The LV end diastolic volume was increased from 65 +/- 22 to 115 +/- 78 ml in tachycardia and 67 +/- 19 to 148 +/- 68 ml in volume-overload model. Flow reversal was observed in diastolic phase in carotid artery of both models and femoral artery in volume-overload model. The endothelial function was also significantly impaired in carotid and renal arteries of tachycardia and volume-overload animals. The endothelial dysfunction was observed in femoral artery of volume-overload animals but not tachycardia animals. The adrenergic receptor-dependent contractility decreased in carotid and femoral arteries of tachycardia animals. The protein expressions of NADPH oxidase subunits increased in the three arteries and both animal models while expression of MnSOD decreased in carotid artery of tachycardia and volume-overload model. In conclusion, different HF models lead to variable arterial hemodynamic changes but similar vascular and molecular expression changes that reflect the role of both local hemodynamics as well as systemic changes in HF. PMID- 25127037 TI - Phenotypic modulation of corpus cavernosum smooth muscle cells in a rat model of cavernous neurectomy. AB - BACKGROUND: Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis. AIM: We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats. METHODS: Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). RESULTS: Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia inducible factor-1alpha and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle alpha-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats. CONCLUSIONS: CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury-induced ED. PMID- 25127038 TI - Enhanced biocatalytic esterification with lipase-immobilized chitosan/graphene oxide beads. AB - In this work, lipase from Candida rugosa was immobilized onto chitosan/graphene oxide beads. This was to provide an enzyme-immobilizing carrier with excellent enzyme immobilization activity for an enzyme group requiring hydrophilicity on the immobilizing carrier. In addition, this work involved a process for the preparation of an enzymatically active product insoluble in a reaction medium consisting of lauric acid and oleyl alcohol as reactants and hexane as a solvent. This product enabled the stability of the enzyme under the working conditions and allowed the enzyme to be readily isolated from the support. In particular, this meant that an enzymatic reaction could be stopped by the simple mechanical separation of the "insoluble" enzyme from the reaction medium. Chitosan was incorporated with graphene oxide because the latter was able to enhance the physical strength of the chitosan beads by its superior mechanical integrity and low thermal conductivity. The X-ray diffraction pattern showed that the graphene oxide was successfully embedded within the structure of the chitosan. Further, the lipase incorporation on the beads was confirmed by a thermo-gravimetric analysis. The lipase immobilization on the beads involved the functionalization with coupling agents, N-hydroxysulfosuccinimide sodium (NHS) and 1-ethyl-(3 dimethylaminopropyl) carbodiimide (EDC), and it possessed a high enzyme activity of 64 U. The overall esterification conversion of the prepared product was 78% at 60 degrees C, and it attained conversions of 98% and 88% with commercially available lipozyme and novozyme, respectively, under similar experimental conditions. PMID- 25127039 TI - IGFBP3 methylation is a novel diagnostic and predictive biomarker in colorectal cancer. AB - BACKGROUND AND AIM: Aberrant hypermethylation of cancer-related genes has emerged as a promising strategy for the development of diagnostic, prognostic and predictive biomarkers in human cancer, including colorectal cancer (CRC). The aim of this study was to perform a systematic and comprehensive analysis of a panel of CRC-specific genes as potential diagnostic, prognostic and predictive biomarkers in a large, population-based CRC cohort. PATIENTS AND METHODS: Methylation status of the SEPT9, TWIST1, IGFBP3, GAS7, ALX4 and miR137 genes was studied by quantitative bisulfite pyrosequencing in a population-based cohort of 425 CRC patients. RESULTS: Methylation levels of all genes analyzed were significantly higher in tumor tissues compared to normal mucosa (p<0.0001); however, cancer-associated hypermethylation was most frequently observed for miR137 (86.7%) and IGFBP3 (83%) in CRC patients. Methylation analysis using the combination of these two genes demonstrated greatest accuracy for the identification of colonic tumors (sensitivity 95.5%; specificity 90.5%). Low levels of IGFBP3 promoter methylation emerged as an independent risk factor for predicting poor disease free survival in stage II and III CRC patients (HR = 0.49, 95% CI: 0.28-0.85, p = 0.01). Our results also suggest that stage II & III CRC patients with high levels of IGFBP3 methylation do not benefit from adjuvant 5FU-based chemotherapy. CONCLUSION: By analyzing a large, population-based CRC cohort, we demonstrate the potential clinical significance of miR137 and IGFBP3 hypermethylation as promising diagnostic biomarkers in CRC. Our data also revealed that IGFBP3 hypermethylation may serve as an independent prognostic and predictive biomarker in stage II and III CRC patients. PMID- 25127042 TI - Determination of critical nitrogen dilution curve based on stem dry matter in rice. AB - Plant analysis is a very promising diagnostic tool for assessment of crop nitrogen (N) requirements in perspectives of cost effective and environment friendly agriculture. Diagnosing N nutritional status of rice crop through plant analysis will give insights into optimizing N requirements of future crops. The present study was aimed to develop a new methodology for determining the critical nitrogen (Nc) dilution curve based on stem dry matter (SDM) and to assess its suitability to estimate the level of N nutrition for rice (Oryza sativa L.) in east China. Three field experiments with varied N rates (0-360 kg N ha(-1)) using three Japonica rice hybrids, Lingxiangyou-18, Wuxiangjing-14 and Wuyunjing were conducted in Jiangsu province of east China. SDM and stem N concentration (SNC) were determined during vegetative stage for growth analysis. A Nc dilution curve based on SDM was described by the equation (Nc = 2.17W(-0.27) with W being SDM in t ha(-1)), when SDM ranged from 0.88 to 7.94 t ha(-1). However, for SDM < 0.88 t ha(-1), the constant critical value Nc = 1.76% SDM was applied. The curve was dually validated for N-limiting and non-N-limiting growth conditions. The N nutrition index (NNI) and accumulated N deficit (Nand) of stem ranged from 0.57 to 1.06 and 51.1 to -7.07 kg N ha(-1), respectively, during key growth stages under varied N rates in 2010 and 2011. The values of DeltaN derived from either NNI or Nand could be used as references for N dressing management during rice growth. Our results demonstrated that the present curve well differentiated the conditions of limiting and non-limiting N nutrition in rice crop. The SDM based Nc dilution curve can be adopted as an alternate and novel approach for evaluating plant N status to support N fertilization decision during the vegetative growth of Japonica rice in east China. PMID- 25127040 TI - Toll-like receptor-3 is dispensable for the innate microRNA response to West Nile virus (WNV). AB - The innate immune response to West Nile virus (WNV) infection involves recognition through toll-like receptors (TLRs) and RIG-I-like receptors (RLRs), leading to establishment of an antiviral state. MiRNAs (miRNAs) have been shown to be reliable biomarkers of TLR activation. Here, we sought to evaluate the contribution of TLR3 and miRNAs to the host response to WNV infection. We first analyzed HEK293-NULL and HEK293-TLR3 cells for changes in the innate immune response to infection. The presence of TLR3 did not seem to affect WNV load, infectivity or phosphorylation of IRF3. Analysis of experimentally validated NFkappaB-responsive genes revealed a WNV-induced signature largely independent of TLR3. Since miRNAs are involved in viral pathogenesis and the innate response to infection, we sought to identify changes in miRNA expression upon infection in the presence or absence of TLR3. MiRNA profiling revealed 70 miRNAs induced following WNV infection in a TLR3-independent manner. Further analysis of predicted gene targets of WNV signature miRNAs revealed genes highly associated with pathways regulating cell death, viral pathogenesis and immune cell trafficking. PMID- 25127044 TI - Exploiting monitoring data in environmental exposure modelling and risk assessment of pharmaceuticals. AB - In order to establish the environmental impact of an active pharmaceutical ingredient (API), good information on the level of exposure in surface waters is needed. Exposure concentrations are typically estimated using information on the usage of an API as well as removal rates in the patient, the wastewater system and in surface waters. These input data are often highly variable and difficult to obtain, so model estimates often do not agree with measurements made in the field. In this paper we present an approach which uses inverse modelling to estimate overall removal rates of pharmaceuticals at the catchment scale using a hydrological model as well as prescription and monitoring data for a few representative sites for a country or region. These overall removal rates are then used to model exposure across the broader landscape. Evaluation of this approach for APIs in surface waters across England and Wales showed good agreement between modelled exposure distributions and available monitoring data. The use of the approach, alongside estimates of predicted no-effect concentrations for the 12 study compounds, to assess risk of the APIs across the UK landscape, indicated that, for most of the compounds, risks to aquatic life were low. However, ibuprofen was predicted to pose an unacceptable risk in 49.5% of the river reaches studied. For diclofenac, predicted exposure concentrations were also compared to the Environmental Quality Standard previously proposed by the European Commission and 4.5% of river reaches were predicted to exceed this concentration. While the current study focused on pharmaceuticals, the approach could also be valuable in assessing the risks of other 'down the drain' chemicals and could help inform our understanding of the important dissipation processes for pharmaceuticals in the pathway from the patient to ecological receptors. PMID- 25127041 TI - SPO24 is a transcriptionally dynamic, small ORF-encoding locus required for efficient sporulation in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, meiosis and sporulation are highly regulated responses that are driven in part by changes in RNA expression. Alternative mRNA forms with extended 5' UTRs are atypical in S. cerevisiae, and 5' extensions with upstream open reading frames (uORFs) are even more unusual. Here we characterize the gene YPR036W-A, now renamed SPO24, which encodes a very small (67-amino-acid) protein. This gene gives rise to two mRNA forms: a shorter form throughout meiosis and a longer, 5'-extended form in mid-late meiosis. The latter form includes a uORF for a 14-amino-acid peptide (Spo24u14). Deletion of the downstream ORF (dORF) leads to sporulation defects and the appearance of pseudohyphae-like projections. Experiments with luciferase reporters indicate that the uORF does not downregulate dORF translation. The protein encoded by the dORF (Spo24d67) localizes to the prospore membrane and is differentially phosphorylated during meiosis. Transcription of the 5'-extended mRNA in mid meiosis depends upon the presence of two middle sporulation elements (MSEs). Removal of the MSEs severely inhibits the mid-meiotic appearance of the 5' extended mRNA and limits the ability of plasmid-borne SPO24 to rescue the sporulation defect of a spo24Delta mutant, suggesting that the 5'-extended mRNA is functionally important. These results reveal Spo24d67 as a sporulation-related factor that is encoded by a transcriptionally dynamic, uORF-containing locus. PMID- 25127045 TI - Diagnostic and therapeutic challenges. PMID- 25127043 TI - Antibiotic resistance genes in bacterial and bacteriophage fractions of Tunisian and Spanish wastewaters as markers to compare the antibiotic resistance patterns in each population. AB - The emergence and increased prevalence of antibiotic resistance genes (ARGs) in the environment may pose a serious global health concern. This study evaluates the abundance of several ARGs in bacterial and bacteriophage DNA via real-time qPCR in samples from five different sampling points in Tunisia; three wastewater treatment plants (WWTP 1, 2 and 3) and wastewater from two abattoirs slaughtering different animals. Results are compared with those obtained in the Barcelona area, in northeast Spain. Eight ARGs were quantified by qPCR from total and phage DNA fraction from the samples. Three beta-lactamases (bla(TEM), bla(CTX-M) cluster 1 and bla(CTX-M) cluster 9), two quinolone resistance genes (qnrA and qnrS), the mecA gene that confers resistance to methicillin in Staphylococcus aureus, the emerging armA gene, conferring resistance to aminoglycosides and sul1, the most extended gene conferring resistance to sulfonamides, were evaluated. Sul1 and bla(TEM) were the most prevalent ARGs detected at all five Tunisian sampling points, similarly with the observations in Barcelona. bla(CTX-M 9) was more prevalent than bla(CTX-M-1) both in bacterial and DNA within phage particles in all samples analysed. mecA and armA were almost absent in Tunisian waters from human or animal origin in contrast with Barcelona that showed a medium prevalence. qnrA was more prevalent than qnrS in bacterial and phage DNA from all sampling points. In conclusion, our study shows that ARGs are found in the bacterial and is reflected in the phage DNA fraction of human and animal wastewaters. The densities of each ARGs vary depending on the ARGs shed by each population and is determined by the characteristics of each area. Thus, the evaluation of ARGs in wastewaters seems to be suitable as marker reflecting the antibiotic resistance patterns of a population. PMID- 25127046 TI - Spectral domain optical coherence tomography findings in long-term silicone oil related visual loss. AB - PURPOSE: To investigate spectral domain optical coherence tomography findings in long-term silicone oil-related visual loss. METHODS: Four symptomatic patients were reviewed 4 years to 9 years after vitrectomy with silicone oil tamponade for macula-on retinal detachment. Three lost vision with oil in situ, with one at the time of oil removal. Eleven control eyes with good vision were included. Patients underwent assessment of best-corrected visual acuity, contrast sensitivity, Farnsworth-Munsell 100 Hue testing, static perimetry, and spectral domain optical coherence tomography imaging of the macula and disk. RESULTS: Long-term best corrected visual acuity was significantly reduced in affected eyes (range, 0.44 1.02), as was contrast sensitivity (0.75-1.35) and color discrimination (Farnsworth-Munsell-100 Hue score, 151-390). Static perimetry showed a central scotoma in all affected eyes. Optical coherence tomography revealed microcystic macular changes in the inner nuclear layer of all affected eyes associated with severe loss of the papillofoveal retinal nerve fiber layer. In one patient, serial optical coherence tomography images showed development of microcystic macular changes 18 months after oil removal. Control eyes lacked these features, except two asymptomatic eyes that showed microcystic changes on optical coherence tomography with a corresponding paracentral scotoma. CONCLUSION: We have demonstrated microcystic macular changes in the inner nuclear layer of affected eyes, as well as focal severe loss of the papillofoveal projection. These changes share significant morphologic features reported in multiple sclerosis-associated optic neuritis and Leber hereditary optic neuropathy. PMID- 25127047 TI - Retinal detachment associated with ocular toxoplasmosis. AB - PURPOSE: To assess the frequency of retinal detachment (RD) and associated clinical features in ocular toxoplasmosis. METHODS: A review of the medical records of patients diagnosed with ocular toxoplasmosis and follow-up of 6 months or more was conducted. All patients were seen at the Casey Eye Institute at the Oregon Health & Science University over a 9-year period (2003-2012). Demographic data, presence of RD and/or vitritis, and treatments were reviewed. Main outcome measures were the rate of RD in ocular toxoplasmosis, degree of vision loss, and final anatomical status of the retina. Disease- and treatment-related factors associated with poor visual outcome were also analyzed. RESULTS: Thirty-five eyes of 28 patients with ocular toxoplasmosis and sufficient follow-up were studied. Median age of patients was 40 years (range, 7-93 years). Median follow-up time was 22.5 months (range, 6-96 months). Four of thirty-five eyes (11.4%) developed RD with a frequency of 0.06 RD events per patient-year of follow-up in this sample in a single center. Of four patients with RD, three underwent pars plana vitrectomy and one underwent laser retinopexy. Two of the 4 patients had recurrent RD requiring scleral buckle. At final follow-up, all patients who underwent surgical repair had attached retinas; however, 3 of 4 patients had severe vision loss (20/200 or worse). CONCLUSION: Retinal detachment occurred in 11% of eyes in this study that led to severe vision loss despite successful RD repair. PMID- 25127048 TI - A 10-year review of open-globe trauma in elderly patients at an urban hospital. AB - BACKGROUND: To describe the demographics, characteristics, and outcomes of open globe injuries (OGIs) in elderly patients. METHODS: Retrospective chart review. RESULTS: Ninety cases (26 men) were identified. The average age was 80 years (range, 65-96 years). The types of OGIs included rupture (83.3%) and penetrating (16.7%) injuries. The causes of trauma were falls (64.4%), accidents (20%), motor vehicle accidents (5.5%), and assault (3.33%). Types of lacerations included corneal (44.4%), corneoscleral (26.7%), and scleral (28.9%). Forty-six cases were OGIs because of dehiscence of previous ocular surgical wound. Ten eyes had concurrent orbital fractures. Approximately 81.1% of cases underwent primary OGI repair within 24 hours of injury, and all cases underwent primary OGI repair within 24 hours of admission. The average visual acuity at presentation was 20/4,375 (SD, 0.64). Although 22 patients presented with no light perception, only 10 remained no light perception after OGI repair. Complications at presentation included uveal prolapse (70%), hemorrhagic choroidal detachment (37.8%), vitreous hemorrhage (51.1%), retinal detachment (20%), and afferent pupillary defect (42.2%). Three patients (3.33%) underwent primary pars plana vitrectomy for retinal detachment and vitreous hemorrhage. Three patients developed endophthalmitis. Overall, retinal attachment was achieved in all eyes that underwent primary pars plana vitrectomy. Primary enucleations were performed in 4 cases (4.44%) for nonsalvageable no light perception eyes. CONCLUSION: The visual prognosis of OGIs in the elderly population is poor; only 14.4% achieved 20/200 or better visual acuity. Precautionary measures should be taken to prevent OGIs in the elderly population. PMID- 25127050 TI - Low-intensity/high-density subthreshold microPulse diode laser for chronic central serous chorioretinopathy. AB - PURPOSE: To evaluate the visual outcomes and macular thickness change in patients with symptomatic chronic central serous chorioretinopathy after treatment with a subthreshold MicroPulse diode laser. METHODS: In this retrospective, interventional case series, 10 patients were treated with the subthreshold 810-nm diode MicroPulse laser. Selected patients had symptomatic disease that may or may not have involved the foveal center. The MicroPulse laser was applied to the areas of leakage seen on fluorescein angiogram, over the areas of clinical neurosensory detachment, and/or pigment epithelial detachments. Pretreatment and posttreatment vision, change in maximum macular thickness, number of treatment sessions, and number of laser spot applications were recorded. Patients were excluded if they did not attend follow-up, had other confounding macular diseases, were using steroid medications, or application of another treatment modality had been used (i.e., photodynamic therapy or anti-vascular endothelial growth factor medication). RESULTS: Ten patients met the inclusion criteria, with 1 patient treated in both eyes. Three patients were excluded for lack of follow up, one for the use of systemic steroids, and one for treatment with anti vascular endothelial growth factor injection. Maximum macular thickness decreased after subthreshold MicroPulse laser treatment between 20 MUm and 338 MUm (mean = 97 MUm decrease, P = 0.0046) in 11 treated eyes. CONCLUSION: Subthreshold diode MicroPulse laser is a potential treatment option for patients with symptomatic chronic central serous chorioretinopathy. PMID- 25127049 TI - Obstructive sleep apnea and central serous chorioretinopathy. AB - PURPOSE: The purpose of this study was to determine if there is an association between obstructive sleep apnea (OSA) and central serous chorioretinopathy (CSCR). METHODS: Patients with CSCR without a history of steroid use or secondary retinal disease were matched based on age/gender/body mass index with control patients and administered the Berlin Questionnaire to assess for OSA risk. Patients were scored "OSA+" if they were at "high risk" on the Berlin Questionnaire or reported a previous OSA diagnosis. Rates of OSA+ were compared between the 2 groups, odds ratio and its 95% confidence interval was calculated using exact conditional logistic regression. RESULTS: Forty-eight qualifying patients with CSCR were identified. There were no statistically significant differences between the CSCR and control groups by age (mean = 55 years), gender (79% male), body mass index (mean = 28.2), history of diabetes, or hypertension. Within the CSCR group, 22 patients (45.8%) were OSA+ versus 21 control patients (43.8%) (difference = 2.1%; 95% confidence interval, -18.2% to 22.2%; exact odds ratio = 1.08, 95% confidence interval, 0.47-2.49; P = 1.00). CONCLUSION: When compared with matched controls, patients with CSCR did not have statistically significant higher rates of OSA risk or previous diagnosis. This finding contrasts with previous work showing a strong association between the diseases. The divergence is likely due to our matching controls for body mass index, a significant risk factor for OSA. PMID- 25127051 TI - Re: Multimodal imaging findings in retinal deep capillary ischemia. PMID- 25127052 TI - Re: Subretinal hyperreflective exudation associated with neovascular age-related macular degeneration. PMID- 25127053 TI - Reply: To PMID 24240565. PMID- 25127054 TI - Reply: To PMID 24695062. PMID- 25127055 TI - Priming and activation of NADPH oxidases in plants and animals. AB - In mammals, engagement of Toll-like receptors by microbe-associated molecular patterns enhances the responsiveness of NADPH oxidases. Two recent papers report a similar 'priming' mechanism for the plant oxidase RbohD. Despite lacking structural homology, the functional parallels between plants and animals reveal that a common regulatory logic arose by convergent evolution. PMID- 25127058 TI - Myeloma genetics and genomics: practice implications and future directions. AB - Multiple myeloma (MM) is a heterogeneous, clonal disorder of the plasma cells originating from the B-cell line. The diagnosis and monitoring of MM requires routine measurement of biomarkers such as serum protein electrophoresis, urine protein electrophoresis, serum free light chains, among others. Prognostic models such as the Durie-Salmon staging system and International Staging System are available and account for the disease burden. Advanced biomarker and genetic testing includes cytogenetics, fluorescent in situ hybridization, and gene expression profiling to estimate the aggressiveness of the disease and personalize the patient's treatment. Future goals of therapy will be to achieve minimal residual disease (MRD), which incorporates biomarkers and genomic data. MRD testing might provide a better estimate of the depth of response to therapy and overall survival. A robust genomic program of research is still needed to provide additional information for the best MM care practices and to gain new strategies to treat the disease, in particular, in the relapsed and/or refractory setting. PMID- 25127059 TI - Large myocardial infarction with myocardium calcium deposits associated with reperfusion injury. AB - The clinical and autopsy findings of a 66-year-old man with myocardial infarction complicated by reperfusion injury are described, highlighting the presence of large myocardium calcium deposits. PMID- 25127056 TI - Notch and hippo converge on Cdx2 to specify the trophectoderm lineage in the mouse blastocyst. AB - The first lineage choice in mammalian embryogenesis is that between the trophectoderm, which gives rise to the trophoblast of the placenta, and the inner cell mass, from which is derived the embryo proper and the yolk sac. The establishment of these lineages is preceded by the inside-versus-outside positioning of cells in the early embryo and stochastic expression of key transcription factors, which is then resolved into lineage-restricted expression. The regulatory inputs that drive this restriction and how they relate to cell position are largely unknown. Here, we show an unsuspected role of Notch signaling in regulating trophectoderm-specific expression of Cdx2 in cooperation with TEAD4. Notch activity is restricted to outer cells and is able to influence positional allocation of blastomeres, mediating preferential localization to the trophectoderm. Our results show that multiple signaling inputs at preimplantation stages specify the first embryonic lineages. PMID- 25127057 TI - TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition. AB - Autophagy, a homeostatic process whereby eukaryotic cells target cytoplasmic cargo for degradation, plays a broad role in health and disease states. Here we screened the TRIM family for roles in autophagy and found that half of TRIMs modulated autophagy. In mechanistic studies, we show that TRIMs associate with autophagy factors and act as platforms assembling ULK1 and Beclin 1 in their activated states. Furthermore, TRIM5alpha acts as a selective autophagy receptor. Based on direct sequence-specific recognition, TRIM5alpha delivered its cognate cytosolic target, a viral capsid protein, for autophagic degradation. Thus, our study establishes that TRIMs can function both as regulators of autophagy and as autophagic cargo receptors, and reveals a basis for selective autophagy in mammalian cells. PMID- 25127060 TI - Youth, friendship, and gaming: a network perspective. AB - With digital games being part of the leisure of a multitude of young people, it is important to understand to what extent gaming-related practices such as talking about games or playing games together are associated with the quality of friendship relations with players and nonplayers. Based on 100 friendship networks, this study explored to what extent those practices permeated the everyday life of youngsters and whether they could be considered as a part of doing friendship. Results indicated that gaming as a conversational topic was widespread within and between networks. Furthermore, regardless of gender, this was significantly associated with friendship quality in almost all of the networks. When considering playing games together, a somewhat different picture emerged. In contrast to conversational practices, playing together was less widespread. Moreover, both the occurrence and the effect of co-play and friendship quality was gendered. The findings of this study show that a focus on gaming-related practices yields a fruitful starting point when considering the role of digital games in a social context that is not limited to people playing (online) games. Furthermore, they also feed into the ongoing debate of possible effects of digital games in that it shows that the way in which games influence the lives of young people goes beyond a direct effects approach. PMID- 25127061 TI - [Latent chronic eosinophilic pneumonia in a patient previously treated with immunomodulators]. PMID- 25127063 TI - Prognostic factors of long-term outcome in cases of severe traumatic brain injury. AB - INTRODUCTION: The purpose of this monocentric study was to assess the long-term outcome of a group of severe traumatic brain-injured patients and explore the prognostic values of some clinical and paraclinical parameters available at the initial stage. METHODOLOGY: The patients included were victims of severe traumatic brain injuries in 2007 or 2008. A standardized assessment was performed for each patient including clinical, radiological, and electrophysiological data collected at the initial stage, The outcomes were assessed at least 2 years after injury. Depending on the patients' availability and ability to communicate, the assessments included measures of dependency for activities of daily living (ADL), cognitive functions, behaviour, mood, and quality of life. RESULTS: Eighteen patients were included, of whom ten were autonomous for ADL at the time of assessment. Memory complaints, attentional deficits, anxiety, and irritability were the main long-term impairments observed. A correlation analysis showed significant correlations between the dependency level (as rated by the Functional Independence Measure) and each of length of coma, length of the post-traumatic amnesia, and the N100 auditory evoked potentials. DISCUSSION: These results confirm the uniqueness of each patient regarding the long-term consequences of a traumatic brain injury and the multi-determined nature of each prognosis. PMID- 25127062 TI - HIV-1 transgenic rats display alterations in immunophenotype and cellular responses associated with aging. AB - Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV 1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg) rat model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS) to determine immunological alterations during the aging process. LPS is known to cause an imbalance in cytokine and chemokine release, and provides a method to identify changes in immune responses to bacterial infection in an HIV animal model. An immune profile and accompanying cellular consequences as well as changes in inflammatory cytokine and chemokine release related to age and genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with age, particularly T cytotoxic cells, whereas T helper cells increased with age. Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-alpha, along with an increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our data indicate that immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients. PMID- 25127065 TI - Partial purification and characterization of chromate reductase of a novel Ochrobactrum sp. strain Cr-B4. AB - Hexavalent chromium contamination is a serious problem due to its high toxicity and carcinogenic effects on the biological systems. The enzymatic reduction of toxic Cr(VI) to the less toxic Cr(III) is an efficient technology for detoxification of Cr(VI)-contaminated industrial effluents. In this regard, a chromate reductase enzyme from a novel Ochrobactrum sp. strain Cr-B4, having the ability to detoxify Cr(VI) contaminated sites, has been partially purified and characterized. The molecular mass of this chromate reductase was found to be 31.53 kD, with a specific activity 14.26 U/mg without any addition of electron donors. The temperature and pH optima for chromate reductase activity were 40 degrees C and 8.0, respectively. The activation energy (Ea) for the chromate reductase was found to be 34.7 kJ/mol up to 40 degrees C and the activation energy for its deactivation (Ed) was found to be 79.6 kJ/mol over a temperature range of 50-80 degrees C. The frequency factor for activation of chromate reductase was found to be 566.79 s(-1), and for deactivation of chromate reductase it was found to be 265.66 * 10(3) s(-1). The reductase activity of this enzyme was affected by the presence of various heavy metals and complexing agents, some of which (ethylenediamine tetraacetic acid [EDTA], mercaptoethanol, NaN3, Pb(2+), Ni(2+), Zn(2+), and Cd(2+)) inhibited the enzyme activity, while metals like Cu(2+) and Fe(3+) significantly enhanced the reductase activity. The enzyme followed Michaelis-Menten kinetics with Km of 104.29 uM and a Vmax of 4.64 uM/min/mg. PMID- 25127064 TI - Motor function levels and pelvic parameters in walking or ambulating children with cerebral palsy. AB - BACKGROUND: In children with cerebral palsy, spinal equilibrium and pelvic strategies may vary according to the functional status. OBJECTIVES: To study the relationship between motor function and pelvic and spinal parameters in a population of children and adolescents with cerebral palsy (rated from level I to level IV on Gross Motor Function Classification System [GMFCS]). A sagittal X-ray of the spine in the standing position was analyzed with Optispine((r)) software. RESULTS: The study population comprised 114 children and adolescents (mean [range] age: 12.35 [4-17]). For the study population as a whole, there were significant overall correlations between the GMFCS level on one hand and pelvic incidence and pelvic tilt (PT) on the other (P=0.013 and 0.021, respectively). DISCUSSION: Pelvic parameters vary according to the GMFCS level but do not appear to affect spinal curvature. The sacrum is positioned in front of the head of the femur (i.e. negative PT) in GMFCS level I and progressively moves backwards (i.e. positive PT) in GMFCS levels II, III and IV. PMID- 25127066 TI - First-order kinetics of landfill leachate treatment in a pilot-scale anaerobic sequence batch biofilm reactor. AB - This paper reports the kinetics evaluation of landfill leachate anaerobic treatment in a pilot-scale Anaerobic Sequence Batch Biofilm Reactor (AnSBBR). The experiment was carried out at room temperature (23.8 +/- 2.1 degrees C) in the landfill area in Sao Carlos-SP, Brazil. Biomass from the bottom of a local landfill leachate stabilization pond was used as inoculum. After acclimated and utilizing leachate directly from the landfill, the AnSBBR presented efficiency over 70%, in terms of COD removal, with influent COD ranging from 4825 mg L(-1) to 12,330 mg L(-1). To evaluate the kinetics of landfill leachate treatment, temporal profiles of CODFilt. concentration were performed and a first-order kinetics model was adjusted for substrate consumption, obtaining an average k1 = 4.40 * 10(-5) L mgTVS(-1) d(-1), corrected to 25 degrees C. Considering the temperature variations, a temperature-activity coefficient theta = 1.07 was obtained. Statistical "Randomness" and "F" tests were used to successfully validate the model considered. Thus, the results demonstrate that the first-order kinetic model is adequate to model the anaerobic treatment of the landfill leachate in the AnSBBR. PMID- 25127067 TI - Delayed vocal fold paralysis after continuous interscalene level brachial plexus block with catheter placement: a case report. AB - We report an incident of delayed onset of true vocal fold paralysis with continuous interscalene brachial plexus block. A 51 year old woman underwent left shoulder manipulation and lysis of adhesions with fluoroscopy and general anesthesia. An interscalene brachial plexus block was performed and a catheter with a continuous infusion pump was placed for postoperative pain control. Following hospital discharge, approximately 8 hours after the initial catheter bolus the patient developed hoarseness, dysphagia, and dyspnea, secondary to left vocal fold palsy. The patient was admitted for observation and the catheter was discontinued with no intubation required. By the next morning, the patient's dysphagia and dyspnea had resolved and her hoarseness improved. PMID- 25127068 TI - Semicarbazide - from state-of-the-art analytical methods and exposure to toxicity: a review. AB - This review assesses the state of the art concerning semicarbazide (SEM). Originally, SEM was primarily detected as a nitrofurazone veterinary metabolite, but over time scientists gradually found that azodicarbonamide in sealed cans and flour could also lead to the generation of SEM. This discovery makes the study of SEM particularly interesting. At present, an increasing number of researchers are investigating the toxicity of SEM and developing more and better analytical methods for the determination of SEM. In recent years, many researchers have focused on exposure from different foods, the public awareness of hazards and analytical detection methods for SEM in different foods. Although there have been significant achievements, these results have not been summarised in a review. The exposure from different foods, toxicity and methods of detection for SEM are comprehensively reviewed here. This review will provide not only others with a better understanding of SEM but also background information to facilitate future research. PMID- 25127070 TI - Transparent and flexible supercapacitors with single walled carbon nanotube thin film electrodes. AB - We describe a simple process for the fabrication of transparent and flexible, solid-state supercapacitors. Symmetric electrodes made up of binder-free single walled carbon nanotube (SWCNT) thin films were deposited onto polydimethylsiloxane substrates by vacuum filtration followed by a stamping method, and solid-state supercapacitor devices were assembled using a gel electrolyte. An optical transmittance of 82% was found for 0.02 mg of SWCNTs, and a specific capacitance of 22.2 F/g was obtained. The power density can reach to 41.5 kW . kg(-1) and shows good capacity retention (94%) upon cycling over 500 times. Fabricated supercapacitors will be relevant for the realization of transparent and flexible devices with energy storage capabilities, displays and touch screens in particular. PMID- 25127069 TI - Comparative angioprotective effects of magnesium compounds. AB - Magnesium (Mg) deficiency is implicated in the development of numerous disorders of the cardiovascular system. Moreover, the data regarding the efficacy of different magnesium compounds in the correction of impaired functions due to low magnesium intake are often fragmentary and inconsistent. The aim of this study was to compare the effects of the most bioavailable Mg compounds (Mg l-aspartate, Mg N-acetyltaurate, Mg chloride, Mg sulphate and Mg oxybutyrate) on systemic inflammation and endothelial dysfunction in rats fed a low Mg diet for 74 days. A low Mg diet decreased the Mg concentration in the plasma and erythrocytes, which was accompanied by a reduced concentration of eNOs and increased levels of endothelin-1 level in the serum and impaired endothelium-dependent vasodilatation. These effects increased the concentration of proinflammatory molecules, such as VCAM-1, TNF-alpha, IL-6 and CRP, indicating the development of systemic inflammation and endothelial dysfunction. The increased total NO level, which estimated from the sum of the nitrate and nitrite concentrations in the serum, may also be considered to be a proinflammatory marker. Two weeks of Mg supplementation partially or fully normalised the ability of the vascular wall to effect adequate endothelium-dependent vasodilatation and reversed the levels of most endothelial dysfunction and inflammatory markers (except CRP) to the mean values of the control group. Mg sulphate had the smallest effect on the endothelin-1, TNF-alpha and VCAM-1 levels. Mg N-acetyltaurate was significantly more effective in restoring the level of eNOS compared to all other studied compounds, except for Mg oxybutyrate. Taken together, the present findings demonstrate that all Mg compounds equally alleviate endothelial dysfunction and inflammation caused by Mg deficiency. Mg sulphate tended to be the least effective compound. PMID- 25127072 TI - Historical Mercury releases from commercial products: global environmental implications. AB - The intentional use of mercury (Hg) in products and processes ("commercial Hg") has contributed a large and previously unquantified anthropogenic source of Hg to the global environment over the industrial era, with major implications for Hg accumulation in environmental reservoirs. We present a global inventory of commercial Hg uses and releases to the atmosphere, water, soil, and landfills from 1850 to 2010. Previous inventories of anthropogenic Hg releases have focused almost exclusively on atmospheric emissions from "byproduct" sectors (e.g., fossil fuel combustion). Cumulative anthropogenic atmospheric Hg emissions since 1850 have recently been estimated at 215 Gg (only including commercial Hg releases from chlor-alkali production, waste incineration, and mining). We find that other commercial Hg uses and nonatmospheric releases from chlor-alkali and mining result in an additional 540 Gg of Hg released to the global environment since 1850 (air: 20%; water: 30%; soil: 30%; landfills: 20%). Some of this release has been sequestered in landfills and benthic sediments, but 310 Gg actively cycles among geochemical reservoirs and contributes to elevated present day environmental Hg concentrations. Commercial Hg use peaked in 1970 and has declined sharply since. We use our inventory of historical environmental releases to force a global biogeochemical model that includes new estimates of the global burial in ocean margin sediments. Accounting for commercial Hg releases improves model consistency with observed atmospheric concentrations and associated historical trends. PMID- 25127071 TI - Complementary and alternative medicine use in infertility: cultural and religious influences in a multicultural Canadian setting. AB - OBJECTIVES: To explore the use of complementary and alternative medicine (CAM) for infertility in a multicultural healthcare setting and to compare Western and non-Western infertility patients' reasons for using CAM and the meanings they attribute to CAM use. DESIGN: Qualitative semi-structured interviews using thematic analysis. SETTINGS/LOCATION: Two infertility clinics in Montreal, Quebec, Canada. PARTICIPANTS: An ethnoculturally varied sample of 32 heterosexual infertile couples. RESULTS: CAM used included lifestyle changes (e.g., changing diet, exercise), alternative medicine (e.g., acupuncture, herbal medicines), and religious methods (e.g., prayers, religious talismans). Patients expressed three attitudes toward CAM: desperate hope, casual optimism, and amused skepticism. PARTICIPANTS' CAM use was consistent with cultural traditions of health and fertility: Westerners relied primarily on biomedicine and used CAM mainly for relaxation, whereas non-Westerners' CAM use was often influenced by culture specific knowledge of health, illness and fertility. CONCLUSIONS: Understanding patients' CAM use may help clinicians provide culturally sensitive, patient centered care. PMID- 25127073 TI - Facilitators and Barriers to Implementing Screening, Brief Intervention, and Referral to Treatment (SBIRT) in Primary Care in Integrated Health Care Settings. AB - BACKGROUND: Substance abuse in the United States is a serious public health concern impacting morbidity and mortality. However, systematic screening and intervention has not been widely adopted into routine practice by health care organizations and routine screening and intervention is not currently in place for primary care at Kaiser Permanente Colorado. Therefore, a formative evaluation was conducted to explore and enhance implementation of the Substance Abuse and Mental Health Services Administration (SAMHSA) screening, brief intervention, and referral to treatment (SBIRT) approach in the organization. METHODS: Key clinical stakeholders, including internal and family medicine physicians, primary care nurses, mental health therapists, chemical dependency clinicians, and clinic based psychologists provided feedback. Two focus groups were also conducted with patient stakeholders: one in English and one in Spanish. RESULTS: All clinical stakeholders promoted clinic-based psychologists to conduct brief intervention and determine referral to treatment as the optimal implementation program. Inclusion of the patient perspective also highlighted the importance of considering this perspective in implementation. Both patient groups were generally supportive of SBIRT, especially the educational value of screening questions defining healthy drinking limits; however, English-speaking patients noted privacy concerns and Spanish-speaking patients noted frequently being asked about drug or alcohol use. Organizationally, systems exist to facilitate drug and alcohol use screening, intervention, and referral to treatment. However, physician time, alignment with other priorities, and lack of consistent communication were noted potential barriers to SBIRT implementation. CONCLUSIONS: Clinicians expressed concerns about competing priorities and the need for organizational leadership involvement for successful SBIRT implementation. A unique suggestion for successful implementation is to utilize existing primary care clinic-based psychologists to conduct brief intervention and facilitate referral to treatment. Patient stakeholders supported universal screening, but cultural differences in opinions and current experience were noted, indicating the importance of including this perspective when evaluating implementation potential. PMID- 25127074 TI - Conserved electrostatic fields at the Ras-effector interface measured through vibrational Stark effect spectroscopy explain the difference in tilt angle in the Ras binding domains of Raf and RalGDS. AB - Vibrational Stark effect (VSE) spectroscopy was used to measure the electrostatic fields present at the interface of the human guanosine triphosphatase (GTPase) Ras docked with the Ras binding domain (RBD) of the protein kinase Raf. Nine amino acids located on the surface of Raf were selected for labeling with a nitrile vibrational probe. Eight of the probe locations were situated along the interface of Ras and Raf, and one probe was 2 nm away on the opposite side of Raf. Vibrational frequencies of the nine Raf nitrile probes were compared both in the monomeric, solvated protein and when docked with wild-type (WT) Ras to construct a comprehensive VSE map of the Ras-Raf interface. Molecular dynamics (MD) simulations employing an umbrella sampling strategy were used to generate a Boltzmann-weighted ensemble of nitrile positions in both the monomeric and docked complexes to determine the effect that docking has on probe location and orientation and to aid in the interpretation of VSE results. These results were compared to an identical study that was previously conducted on nine nitrile probes on the RBD of Ral guanidine dissociation stimulator (RalGDS) to make comparisons between the docked complexes formed when either of the two effectors bind to WT Ras. This comparison finds that there are three regions of conserved electrostatic fields that are formed upon docking of WT Ras with both downstream effectors. Conservation of this pattern in the docked complex then results in different binding orientations observed in otherwise structurally similar proteins. This work supports an electrostatic cause of the known binding tilt angle between the Ras-Raf and Ras-RalGDS complexes. PMID- 25127076 TI - Dynamics of Back Electron Transfer in Dye-Sensitized Solar Cells Featuring 4-tert Butyl-Pyridine and Atomic-Layer-Deposited Alumina as Surface Modifiers. AB - A series of dye-sensitized solar cells (DSCs) was constructed with TiO2 nanoparticles and N719 dye. The standard I3(-)/I(-) redox shuttle and the Co(1,10 phenanthroline)3(3+/2+) shuttle were employed. DSCs were modified with atomic layered-deposited (ALD) coatings of Al2O3 and/or with the surface-adsorbing additive 4-tert-butyl-pyridine. Current-voltage data were collected to ascertain the influence of each modification upon the back electron transfer (ET) dynamics of the DSCs. The primary effect of the additives alone or in tandem is to increase the open-circuit voltage. A second is to alter the short-circuit current density, JSC. With dependence on the specifics of the system examined, any of a myriad of dynamics-related effects were observed to come into play, in both favorable (efficiency boosting) and unfavorable (efficiency damaging) ways. These effects include modulation of (a) charge-injection yields, (b) rates of interception of injected electrons by redox shuttles, and (c) rates of recombination of injected electrons with holes on surface-bound dyes. In turn, these influence charge-collection lengths, charge-collection yields, and onset potentials for undesired dark current. The microscopic origins of the effects appear to be related mainly to changes in driving force and/or electronic coupling for underlying component redox reactions. Perhaps surprisingly, only a minor role for modifier-induced shifts in conduction-band-edge energy was found. The combination of DSC-efficiency-relevant effects engendered by the modifiers was found to vary substantially as a function of the chemical identity of the redox shuttle employed. While types of modifiers are effective, a challenge going forward will be to construct systems in ways in which the benefits of organic and inorganic modifiers can be exploited in fully additive, or even synergistic, fashion. PMID- 25127078 TI - Membrane surface engineering for protein separations: experiments and simulations. AB - A bisphosphonate derived ligand was successfully synthesized and grafted from the surface of regenerated cellulose membrane using atom transfer radical polymerization (ATRP) for protein separations. This ligand has a remarkable affinity for arginine (Arg) residues on protein surface. Hydrophilic residues N (2-hydroxypropyl) methacrylamide (HPMA) was copolymerized to enhance the flexibility of the copolymer ligand and further improve specific protein adsorption. The polymerization of bisphosphonate derivatives was successful for the first time using ATRP. Static and dynamic binding capacities were determined for binding and elution of Arg rich lysozyme. The interaction mechanism between the copolymer ligand and lysozyme was elucidated using classical molecular dynamics (MD) simulations. PMID- 25127075 TI - Reactivity of damaged pyrimidines: DNA cleavage via hemiaminal formation at the C4 positions of the saturated thymine of spore photoproduct and dihydrouridine. AB - Described here are mechanistic details of the chemical reactivities of two modified/saturated pyrimidine residues that represent naturally occurring forms of DNA damage: 5-thyminyl-5,6-dihydrothymine, commonly referred to as the "spore photoproduct" (SP), and 5,6-dihydro-2'-deoxyuridine (dHdU), formed via ionizing radiation damage to cytosine under anoxic conditions and also serving as a general model of saturated pyrimidine residues. It is shown that due to the loss of the pyrimidine C5-C6 double bond and consequent loss of ring aromaticity, the C4 position of both these saturated pyrimidines is prone to the formation of a hemiaminal intermediate via water addition. Water addition is facilitated by basic conditions; however, it also occurs at physiological pH at a slower rate. The hemiaminal species so-formed subsequently converts to a ring-opened hydrolysis product through cleavage of the pyrimidine N3-C4 bond. Further decomposition of this ring-opened product above physiological pH leads to DNA strand break formation. Taken together, these results suggest that once the aromaticity of a pyrimidine residue is lost, the C4 position becomes a "hot spot" for the formation of a tetrahedral intermediate, the decay of which triggers a cascade of elimination reactions that can under certain conditions convert a simple nucleobase modification into a DNA strand break. PMID- 25127077 TI - Gynecologic care for transgender youth. AB - PURPOSE OF REVIEW: To provide an overview of the care of the adolescent transgender patient with regard to the guidelines and recommendations that currently exist, and to review the role of the clinician caring for transgender youth. RECENT FINDINGS: The World Professional Association for Transgender Health and the Endocrine Society continue to provide comprehensive guidelines for the care of adolescent transgender patients. The decision to perform surgery on a patient who is a minor remains a complex one, and a case-by-case approach should be taken with important ethical principles in mind. Cross-sex steroid use places transgender adolescents at risk for metabolic disorders, and careful surveillance is necessary. In addition, transgender teens are at high risk for depression, anxiety and suicidality and have been shown to engage in more high-risk behaviors compared with their nontransgender heterosexual counterparts. SUMMARY: Clinicians who care for adolescents can play an important role in the counseling, screening, health maintenance and support of their patients through the transition process. PMID- 25127079 TI - A nurse-managed advocacy clinic in a Hispanic senior center: using a concept based clinical practice site to enhance nursing education. AB - A nurse-managed advocacy clinic for vulnerable, low-income, non-English-speaking elderly Hispanic men and women was developed at a neighborhood community center as a clinical site for senior baccalaureate nursing students. In the clinic's 5 years of operation, nursing students and faculty provided health screenings and education as well as referrals to primary care providers, landlords, pharmacies, and social workers. In doing so, nursing students were introduced to the concept of patient advocacy in a real-world experiential clinical setting, providing an effective link between theoretical knowledge discussed in the classroom and professional nursing practice. PMID- 25127080 TI - Comparison of student experience with critical events during simulation and acute care hospital rotations. AB - An exploratory study was conducted to determine critical events for adult patients and to verify critical events that nursing students experienced in their nursing programs. Sophomores and juniors were surveyed regarding frequency of exposure to critical events. Sophomores reported greater differences between simulation and clinical practice, with most in simulation. Juniors were more balanced in exposure to critical events, in both clinical practice and simulation. This information provides feedback on critical events, clinical experiences, and how to use simulation to lessen the experience gap. PMID- 25127081 TI - Evaluation of instruments developed to measure the clinical learning environment: an integrative review. AB - The nature of the clinical learning environment has a huge impact on student learning. This article reviews current methods available for evaluating the clinical learning environment. Five instruments were identified that measure the clinical learning environment. All of these instruments focus solely on the student perspective of the clinical learning environment. Although gaining student input is important, there are other perspectives that offer valuable insights on the nature of the clinical learning environment. The findings from this integrative review indicate the need for future development and testing of an instrument to evaluate the clinical learning environment from the staff nurse and nurse faculty perspective. PMID- 25127082 TI - Post-stress rumination predicts HPA axis responses to repeated acute stress. AB - Failure of the hypothalamus-pituitary-adrenal (HPA) axis to habituate to repeated stress exposure is related with adverse health outcomes, but our knowledge of predictors of non-habituation is limited. Rumination, defined as repetitive and unwanted past-centered negative thinking, is related with exaggerated HPA axis stress responses and poor health outcomes. The aim of this study was to test whether post-stress rumination was related with non-habituation of cortisol to repeated stress exposure. Twenty-seven participants (n=13 females) were exposed to the Trier Social Stress Test (TSST) twice on consecutive afternoons. Post stress rumination was measured after the first TSST, and HPA axis responses were assessed by measuring salivary cortisol 1 min before, and 1, 10, 20, 60, and 120 min after both TSSTs. Stress exposure induced HPA axis activation on both days, and this activation showed habituation indicated by lower responses to the second TSST (F=3.7, p=0.015). Post-stress rumination after the first TSST was associated with greater cortisol reactivity after the initial stress test (r=0.45, p<0.05) and with increased cortisol responses to the second TSST (r=0.51, p<0.01), indicating non-habituation, independently of age, sex, depressive symptoms, perceived life stress, and trait rumination. In summary, results showed that rumination after stress predicted non-habituation of HPA axis responses. This finding implicates rumination as one possible mechanism mediating maladaptive stress response patterns, and it might also offer a pathway through which rumination might lead to negative health outcomes. PMID- 25127083 TI - Peptide YY and ghrelin predict craving and risk for relapse in abstinent smokers. AB - Appetite hormones are directly involved in regulating satiety, energy expenditure, and food intake, and accumulating evidence suggests their involvement in regulating reward and craving for drugs. This study investigated the ability of peptide YY (PYY) and ghrelin during the initial 24-48 h of a smoking cessation attempt to predict smoking relapse at 4 weeks. Multiple regression analysis indicated that increased PYY was associated with decreased reported craving and increased positive affect. Cox proportional hazard models showed that higher ghrelin levels predicted increased risk of smoking relapse (hazard ratio=2.06, 95% CI=1.30-3.27). These results indicate that circulating PYY may have buffering effects during the early stages of cessation while ghrelin may confer increased risk of smoking relapse. Further investigation of the links between these hormones and nicotine dependence is warranted. PMID- 25127084 TI - Effect of restorative yoga vs. stretching on diurnal cortisol dynamics and psychosocial outcomes in individuals with the metabolic syndrome: the PRYSMS randomized controlled trial. AB - PURPOSE: Chronic stimulation and dysregulation of the neuroendocrine system by stress may cause metabolic abnormalities. We estimated how much cortisol and psychosocial outcomes improved with a restorative yoga (relaxation) versus a low impact stretching intervention for individuals with the metabolic syndrome. METHODS: We conducted a 1-year multi-center randomized controlled trial (6-month intervention and 6-month maintenance phase) of restorative yoga vs. stretching. Participants completed surveys to assess depression, social support, positive affect, and stress at baseline, 6 months and 12 months. For each assessment, we collected saliva at four points daily for three days and collected response to dexamethasone on the fourth day for analysis of diurnal cortisol dynamics. We analyzed our data using multivariate regression models, controlling for study site, medications (antidepressants, hormone therapy), body mass index, and baseline cortisol values. RESULTS: Psychosocial outcome measures were available for 171 study participants at baseline, 140 at 6 months, and 132 at 1 year. Complete cortisol data were available for 136 of 171 study participants (72 in restorative yoga and 64 in stretching) and were only available at baseline and 6 months. At 6 months, the stretching group had decreased cortisol at waking and bedtime compared to the restorative yoga group. The pattern of changes in stress mirrored this improvement, with the stretching group showing reductions in chronic stress severity and perseverative thoughts about their stress. Perceived stress decreased by 1.5 points (-0.4; 3.3, p=0.11) at 6 months, and by 2.0 points (0.1; 3.9, p=0.04) at 1 year in the stretching compared to restorative yoga groups. Post hoc analyses suggest that in the stretching group only, perceived increases in social support (particularly feelings of belonging), but not changes in stress were related to improved cortisol dynamics. CONCLUSIONS: We found significant decreases in salivary cortisol, chronic stress severity, and stress perception in the stretching group compared to the restorative yoga group. Group support during the interactive stretch classes may have contributed to these changes. PMID- 25127086 TI - Who is stressed? A pilot study of salivary cortisol and alpha-amylase concentrations in agoraphobic patients and their novice therapists undergoing in vivo exposure. AB - In cognitive behavioural therapy of phobic anxiety, in vivo exposure is considered as an effective treatment strategy. Apparently, it involves the experience of stress and anxiety in patients. Given the therapist's role during exposure sessions, it is conceivable that the performance is also accompanied with the experience of stress in therapists, especially when unversed in conducting psychotherapy. Studies confirmed that cognitive behavioural therapists tend to avoid therapist-guided in vivo exposure. The objective of this study was the simultaneous investigation of therapist's and patient's stress response during in vivo exposure. Therefore, 23 agoraphobic patients and their 23 treating therapists in training provided five saliva samples during an in vivo exposure and five samples during an ordinary therapy session. Before and during exposure session, subjective evaluations of stress and anxiety were assessed. Results suggested that therapists reported similar levels of perceived stress as patients before exposure. Both groups displayed significantly elevated salivary cortisol (sC) levels during exposure compared to the control session and a trend for alterations in salivary alpha-amylase (sAA) activity was found. Therapists reached peak concentrations of sC before start of the intervention followed by a decline during exposure, while patients displayed peak levels of cortisol secretion after 60 min of exposure. In vivo exposure seems to be a demanding intervention not only for the patient, but also for therapists in training. However, it was also demonstrated that physiological and subjective stress rather decrease during the intervention and that both groups rated exposure to be substantially successful. Based on the presented results, another potential factor contributing to the under-usage of exposure treatment is conceivable and needs to be addressed in future research. PMID- 25127087 TI - Rewards and challenges of a career in research and teaching at a liberal arts college. PMID- 25127085 TI - Coping and glucocorticoid receptor regulation by stress inoculation. AB - Intermittent exposure to mildly stressful situations provides opportunities to practice coping in the context of exposure psychotherapies and stress inoculation training. Previously, we showed that stress inoculation modeled in juvenile monkeys enhances subsequent indications of resilience. Here we examine stress inoculation effects in adult female monkeys. We found that stress inoculation prevents social separation stress induced anhedonia measured using sucrose preference tests and reduces the hypothalamic pituitary adrenal (HPA) axis stress hormone response to a novel environment. Stress inoculation also increases glucocorticoid receptor (NR3C1) gene expression in anterior cingulate cortex but not hippocampus. Increased anterior cingulate cortex NR3C1 expression induced by stress inoculation is not associated with significant changes in GR1F promoter DNA methylation. On average, low levels of promoter DNA methylation and limited GR1F expression were evident in monkey anterior cingulate cortex as observed in corticolimbic brain regions of adult humans. Taken together these findings suggest that stress inoculation in adulthood enhances behavioral and hormonal aspects of coping without significantly influencing GR1F promoter DNA methylation as a mechanism for NR3C1 transcription regulation. PMID- 25127088 TI - Zebrafish bioassay-guided microfractionation identifies anticonvulsant steroid glycosides from the Philippine medicinal plant Solanum torvum. AB - Medicinal plants used for the treatment of epilepsy are potentially a valuable source of novel antiepileptic small molecules. To identify anticonvulsant secondary metabolites, we performed an in vivo, zebrafish-based screen of medicinal plants used in Southeast Asia for the treatment of seizures. Solanum torvum Sw. (Solanaceae) was identified as having significant anticonvulsant activity in zebrafish larvae with seizures induced by the GABAA antagonist pentylenetetrazol (PTZ). This finding correlates well with the ethnomedical use of this plant in the Philippines, where a water decoction of S. torvum leaves is used to treat epileptic seizures. HPLC microfractionation of the bioactive crude extract, in combination with the in vivo zebrafish seizure assay, enabled the rapid localization of several bioactive compounds that were partially identified online by UHPLC-TOF-MS as steroid glycosides. Targeted isolation of the active constituents from the methanolic extract enabled the complete de novo structure identification of the six main bioactive compounds that were also present in the traditional preparation. To partially mimic the in vivo metabolism of these triterpene glycosides, their common aglycone was generated by acid hydrolysis. The isolated molecules exhibited significant anticonvulsant activity in zebrafish seizure assays. These results underscore the potential of zebrafish bioassay guided microfractionation to rapidly identify novel bioactive small molecules of natural origin. PMID- 25127090 TI - Continuous subcutaneous hydrocortisone infusion therapy in Addison's disease: a randomized, placebo-controlled clinical trial. AB - CONTEXT: Patients with Addison's disease (AD) report impaired subjective health status (SHS). Since cortisol exhibits a robust circadian cycle that entrains other biological clocks, impaired SHS may be due to the noncircadian cortisol profile achieved with conventional glucocorticoid replacement. Continuous subcutaneous hydrocortisone infusion (CSHI) reproduces a circadian cortisol profile, but its effects on SHS have not been objectively evaluated. OBJECTIVE: The aim of this study was to determine the effect of CSHI on SHS in AD. SETTING AND DESIGN: This was a multicentre, double-blind, placebo-controlled trial of CSHI vs oral glucocorticoid therapy. Participants received in random order 4 weeks of: CSHI and oral placebo, and subcutaneous placebo and oral hydrocortisone, separated by a 2-week washout period. SHS was assessed using the Short-Form 36 (SF-36), General Health Questionnaire (GHQ-28), Fatigue Scale (FS), Gastrointestinal Symptom Rating Scale (GSRS); and Addison's Quality of Life Questionnaire (AddiQoL). Participants were asked their (blinded) treatment preference. Twenty-four hour urine free cortisol (UFC) and diurnal salivary cortisol collections compared cortisol exposure during each treatment. RESULTS: Ten participants completed the study. Baseline SHS scores (mean +/- SE) were consistent with mild impairment: SF-36 physical component summary 48.4 (+/- 2.4), mental component summary 53.3 (+/- 3.0); GHQ-28 18.1 (+/- 3.3); GSRS 3.7 (+/- 1.6), and AddiQoL 94.7 (+/- 3.7). FS was similar to other AD cohorts 13.5 (+/- 1.0) (P = 0.82). UFC between treatments was not different (P = 0.87). The salivary cortisol at 0800 h was higher during CSHI (P = 0.03), but not at any other time points measured. There was no difference between the treatments in the SHS assessments. Five participants preferred CSHI, four oral hydrocortisone, and one was uncertain. CONCLUSIONS: Biochemical measurements indicate similar cortisol exposure during each treatment period, although a more circadian pattern was evident during CSHI. CSHI does not improve SHS in AD with good baseline SHS. This casts some doubt on the potential benefit of circadian cortisol delivery on SHS in AD. PMID- 25127091 TI - Normal bone density and fat mass in heterozygous SERPINF1 mutation carriers. AB - CONTEXT: Homozygous mutations in SERPINF1 cause deficiency of pigment epithelium derived factor (PEDF) and lead to osteogenesis imperfecta (OI) type VI, but it is not known whether heterozygous mutations in SERPINF1 cause a phenotype. OBJECTIVE: In the present study, we therefore assessed family members of individuals with OI type VI and compared the results of SERPINF1 mutation carriers with those of noncarriers of SERPINF1 mutations. SETTING: This study was conducted at a metabolic bone clinic of a pediatric orthopedic hospital. SUBJECTS: The study population comprised 29 family members (age range 8-89 y; 18 females, 11 males) of patients with a diagnosis of OI type VI. Eighteen individuals were heterozygous for SERPINF1 mutations, but the others did not carry a mutation. MAIN OUTCOME MEASURES: PEDF expression was assessed in skin fibroblasts from four heterozygous SERPINF1 mutation carriers. Skeletal characteristics and body composition were measured using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Serum samples were used to quantify markers of bone metabolism, lipid status, and PEDF. RESULTS: Carriers of heterozygous stop or frame shift mutations in SERPINF1 had low SERPINF1 transcript levels. Mean PEDF serum concentrations were significantly lower in the carrier group than in the noncarriers (P = .04). However, no group differences were found with regard to areal bone density at the lumbar spine and total body, volumetric bone density at the radius and tibia, body composition, lipid status, and markers of bone metabolism. CONCLUSION: Heterozygous SERPINF1 mutation carriers had no detectable abnormalities in fat and bone, despite decreased PEDF expression. PMID- 25127092 TI - Ectopic prolactin secretion from a perivascular epithelioid cell tumor (PEComa). AB - BACKGROUND: The diagnosis of ectopic pituitary hormone secretion requires abnormally high circulating hormone levels, absence of a pituitary tumor, and localization of the hormone in question to the extrapituitary malignant neoplasm. No case of a malignant solid tumor producing prolactin has been documented thus far. CASE REPORT: A 47-year-old woman presented with amenorrhea and galactorrhea of 3-year duration. Serum prolactin ranged from 300 to > 900 ng/mL, and other pituitary and thyroid indices were normal, including testing for macroprolactinemia. Pituitary magnetic resonance imaging revealed a partially empty sella but no tumor. Cabergoline 0.5 mg twice weekly did not affect her prolactinemia (1700 to 1900 ng/mL), and the medication was stopped. In the meantime, she developed abdominal pain, and a computed tomography scan showed a 17 * 13 * 8-cm mass abutting the distal stomach, proximal duodenum, and right colon. After the tumor was excised, her galactorrhea resolved, menstrual periodicity resumed within the first month, and serum prolactin fell to 5 ng/mL. Pathological examination of the excised tumor was consistent with perivascular epithelioid cell tumor. Between 5 and 10% of the tumor cells were strongly positive for prolactin on immunohistochemistry. RT-PCR detected prolactin mRNA in the tumor cell extract, confirming the diagnosis of ectopic prolactin synthesis and secretion. CONCLUSION: We present the first example of massive and symptomatic hyperprolactinemia due to ectopic prolactin production by a solid extrapituitary mesenchymal tumor confirmed with both mRNA analysis and immunohistochemistry. Ectopic prolactin secretion should be suspected in patients with a prolactin >200 ng/mL and negative sellar MRI. PMID- 25127093 TI - Conjunctival UV autofluorescence--prevalence and risk factors. AB - PURPOSE: Autofluorescence of ultraviolet (UV) light has been shown to occur in localised areas of the bulbar conjunctiva, which map to active cellular changes due to UV and environmental exposure. This study examined the presence of conjunctival UV autofluorescence in eye care practitioners (ECPs) across Europe and the Middle East and its associated risk factors. METHOD: Images were captured of 307 ECPs right eyes in the Czech Republic, Germany, Greece, Kuwait, Netherlands, Sweden, Switzerland, United Arab Emirates and the United Kingdom using a Nikon D100 camera and dual flash units through UV filters. UV autofluorescence was outlined using ImageJ software and the nasal and temporal area quantified. Subjects were required to complete a questionnaire on their demographics and lifestyle including general exposure to UV and refractive correction. RESULTS: Average age of the subjects was 38.5+/-12.2 years (range 19 68) and 39.7% were male. Sixty-two percent of eyes had some conjunctival damage as indicated by UV autofluorescence. The average area of damage was higher (p=0.005) nasally (2.95+/-4.52mm(2)) than temporally (2.19+/-4.17mm(2)). The area of UV damage was not related to age (r=0.03, p=0.674), gender (p=0.194), self reported sun exposure lifestyle (p>0.05), geographical location (p=0174), sunglasses use (p>0.05) or UV-blocking contact lens use (p>0.05), although it was higher in those wearing contact lenses with minimal UV-blocking and no spectacles (p=0.015). The area of UV damage was also less nasally in those who wore contact lenses and spectacles compared to those with no refractive correction use (p=0.011 nasal; p=0.958 temporal). CONCLUSION: UV conjunctival damage is common even in Europe, Kuwait and UAE, and among ECPs. The area of damage appears to be linked with the use of refractive correction, with greater damage nasally than temporally which may be explained by the peripheral light focusing effect. PMID- 25127089 TI - Abnormalities in cortical bone, trabecular plates, and stiffness in postmenopausal women treated with glucocorticoids. AB - CONTEXT: The mechanisms by which glucocorticoids (GCs) increase skeletal fragility are not well understood. OBJECTIVE: The objective of the study was to evaluate the microarchitecture, trabecular morphology, and biomechanical properties of bone in postmenopausal women treated with GCs. DESIGN: This was a case-control study. SETTING: The study was conducted at a university hospital outpatient facility. PATIENTS: Postmenopausal women treated with oral GCs for longer than 3 months (n = 30) and age/race-matched controls (n = 60) participated in the study. MAIN OUTCOME MEASURES: Areal bone mineral density aBMD (BMD) by dual-energy x-ray absorptiometry (DXA) was measured. Trabecular and cortical volumetric BMD (vBMD) and microarchitecture by high-resolution peripheral computed tomography of the distal radius and tibia were also measured. Whole-bone stiffness was estimated by finite element analysis. A novel technique, individual trabecula segmentation, was used to evaluate trabecular type (as plate or rod), orientation, and connectivity. RESULTS: DXA T-scores did not differ significantly at any site. GC subjects had significantly lower total, cortical, and trabecular vBMD and thinner cortices, fewer, thinner, more widely, and irregularly spaced trabeculae. They had fewer trabecular plates, fewer axially aligned trabeculae, and lower trabecular connectivity. Differences ranged from 4% to 65% for these trabecular measures and 5% to 17% for the cortical measures. Whole-bone stiffness was significantly lower (11%-16%) in GC subjects. Markers of bone formation (osteocalcin and amino-terminal propeptide of type I procollagen) and resorption (C-telopeptide) were lower in the GC subjects. CONCLUSIONS: Despite similar areal BMD by DXA, GC-treated women had abnormal cortical and trabecular vBMD and microarchitecture at both the radius and tibia, including fewer trabecular plates, a less axially aligned trabecular network, lower trabecular connectivity, thinner cortices, and lower whole-bone stiffness. Further research into these abnormalities as mechanisms for fracture in GC-treated women is warranted. PMID- 25127094 TI - Rhabdoid differentiation is associated with aggressive behavior in renal cell carcinoma: a clinicopathologic analysis of 76 cases with clinical follow-up. AB - Rhabdoid differentiation has been associated with aggressive behavior in carcinomas from different organ systems. A recent consensus statement of the International Society of Urological Pathology (ISUP), in addition to proposing a nucleolar grading system (ISUP grade) for renal cell carcinoma (RCC) to replace the Fuhrman system, recommended reporting the presence of rhabdoid differentiation in RCC and considering tumors with rhabdoid differentiation to be ISUP grade 4. Although it has been shown that rhabdoid differentiation is associated with increased grade and stage of RCC, it has not been fully demonstrated whether it has an adverse effect independent of this association with increased grade and stage. We provide the largest clinicopathologic analysis of RCC with rhabdoid differentiation to date (76 cases), including characterization of metastatic disease. In addition, by constructing a multivariable model including tumor grade, stage, necrosis, and distant metastasis to compare a series of 49 clear cell RCC with rhabdoid differentiation with a cohort of 41 clear cell RCCs without rhabdoid differentiation, we demonstrate that the presence of rhabdoid differentiation in clear cell RCC confers an increased risk of death (hazard ratio=5.25; 95% confidence interval, 2.1-14.3) independent of these other adverse prognostic factors. These findings underscore the significance of rhabdoid differentiation in RCC as an adverse prognostic factor and support the recent reporting and grading recommendations of the ISUP. PMID- 25127095 TI - Morphologic and molecular characterization of traditional serrated adenomas of the distal colon and rectum. AB - Of the serrated polyps, the origin, morphologic features, molecular alterations, and natural history of traditional serrated adenomas (TSAs) are the least understood. Recent studies suggest that these polyps may arise from precursor lesions. The frequencies of KRAS and BRAF mutations vary between these studies, and only 1 small study has measured CpG island methylation using current markers of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous adenomas, have not been fully evaluated in TSAs. Finally, the expression of annexin A10 (ANXA10), a recently discovered marker of sessile serrated adenomas/polyps, has not been studied in these polyps. To further characterize these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps diagnosed as TSA at a single institution. Pathologists assessed various histologic features including cytoplasmic eosinophilia, ectopic crypt foci, presence of conventional dysplasia, and presence of precursor serrated lesions. KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62% of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which were hyperplastic polyps. KRAS and BRAF mutations were common and were present in 42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps, often in conjunction with a BRAF mutation. Unlike sessile serrated adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF mutated TSAs had more widespread methylation of a 5-marker CpG island panel compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed defining feature of TSA, were not associated with any specific molecular alteration. PMID- 25127096 TI - Estimation of normal computed tomography measurements for the upper cervical spine in the pediatric age group. AB - OBJECT: Upper cervical spine injuries in the pediatric age group have been recognized as extremely unstable from ligamentous disruption and as potentially lethal. Few measurement norms have been published for the pediatric upper cervical spine to help diagnose this pathological state. Instead, adult measurement techniques and results are usually applied inappropriately to children. The authors propose using high-resolution reconstructed CT scans to define a range of normal for a collection of selected upper cervical spine measurements in the pediatric age group. METHODS: Sagittal and coronal reformatted images were obtained from thin axial CT scans obtained in 42 children (< 18 years) in a 2-month period. There were 25 boys and 17 girls. The mean age was 100.9 months (range 1-214 months). Six CT scans were obtained for nontrauma indications, and 36 were obtained as part of a trauma protocol and later cleared for cervical spine injury. Six straightforward and direct linear distances-basion dental interval (BDI); atlantodental interval (ADI); posterior atlantodental interval (PADI); right and left lateral mass interval (LMI); right and left craniocervical interval (CCI); and prevertebral soft-tissue thickness at C-2-that minimized logistical and technical distortions were measured and recorded. Statistical analysis including interobserver agreement, age stratification, and sex differences was performed for each of the 6 measurements. RESULTS: The mean ADI was 2.25 +/- 0.24 mm (+/- SD), the mean PADI was 18.3 +/- 0.07 mm, the mean BDI was 7.28 +/- 0.10 mm, and the mean prevertebral soft tissue width at C-2 was 4.45 +/- 0.43 mm. The overall mean CCI was 2.38 +/- 0.44 mm, and the overall mean LMI was 2.91 +/- 0.49 mm. Linear regression analysis demonstrated statistically significant age effects for PADI (increased 0.02 mm/month), BDI (decreased 0.02 mm/month), and CCI (decreased 0.01 mm/month). Similarly significant effects were found for sex; females demonstrated on average a smaller CCI by 0.26 mm and a smaller PADI by 2.12 mm. Moderate to high interrater reliability was demonstrated across all parameters. CONCLUSIONS: Age-dependent and age-independent normal CT measurements of the upper cervical spine will help to differentiate physiological and pathological states in children. The BDI appears to change significantly with age but not sex; on the other hand, the LMI and ADI appear to be age-independent measures. This preliminary study suggests acceptable levels of interrater reliability, and further expanded study will aim to validate these measurements to produce a profile of normal upper cervical spine measurements in children. PMID- 25127097 TI - Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center. AB - OBJECT: Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. METHODS: Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990-2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. RESULTS: Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2-77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24-34 months) and 9 months (95% CI 6-11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3-1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6 11 months). CONCLUSIONS: The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy. PMID- 25127100 TI - The deformation of B4C particle in the B4C/2024Al composites after high velocity impact. AB - In the present work, B4C/2024Al composites with volume fraction of 45% were prepared by a pressure infiltration method. The microstructure of the crater bottom of B4C/2024Al composite after impact was characterized by transmission electron microscope (TEM), which indicated that recovery and dynamic recrystallization generated in Al matrix, and the grain size distribution was about from dozens of nanometer to 200 nm. Furthermore, the plastic deformation was observed in B4C ceramic, which led to the transformation from monocrystal to polycrystal ceramic grains. The boundary observed in this work was high-angle grain boundary and the two grains at the boundary had an orientation difference of 30 degrees . PMID- 25127099 TI - Enterocutaneous fistula in the setting of ventriculoperitoneal shunt extrusion through the skin and perforation through the small bowel. AB - The authors report a case of a 2-year-old boy with postinfectious hydrocephalus, managed with a ventriculoperitoneal (VP) shunt and complicated by shunt extrusion through the cranial skin. The shunt was removed due to concern for infection, and the child was found to have an enterocutaneous fistula (ECF) communicating along the shunt track between the small bowel and a clavicular sinus. Self-closure of the ECF was anticipated. Thus, the fistula was managed expectantly with dressing changes of the clavicular sinus, while the patient's malnutrition was managed in accordance with World Health Organization protocols. The presentation, prognosis and management of ECFs, including the likelihood of self-resolution and the role of expectant management, are discussed. Additionally, proposed mechanisms of ECF formation in the setting of a VP shunt are discussed, with an emphasis on the roles of infection and malnutrition. PMID- 25127098 TI - Epilepsy surgery failure in children: a quantitative and qualitative analysis. AB - OBJECT: Resection is a safe and effective treatment option for children with pharmacoresistant focal epilepsy, but some patients continue experience seizures after surgery. While most studies of pediatric epilepsy surgery focus on predictors of postoperative seizure outcome, these factors are often not modifiable, and the reasons for surgical failure may remain unclear. METHODS: The authors performed a retrospective cohort study of children and adolescents who received focal resective surgery for pharmacoresistant epilepsy. Both quantitative and qualitative analyses of factors associated with persistent postoperative seizures were conducted. RESULTS: Records were reviewed from 110 patients, ranging in age from 6 months to 19 years at the time of surgery, who underwent a total of 115 resections. At a mean 3.1-year follow-up, 76% of patients were free of disabling seizures (Engel Class I outcome). Seizure freedom was predicted by temporal lobe surgery compared with extratemporal resection, tumor or mesial temporal sclerosis compared with cortical dysplasia or other pathologies, and by a lower preoperative seizure frequency. Factors associated with persistent seizures (Engel Class II-IV outcome) included residual epileptogenic tissue adjacent to the resection cavity (40%), an additional epileptogenic zone distant from the resection cavity (32%), and the presence of a hemispheric epilepsy syndrome (28%). CONCLUSIONS: While seizure outcomes in pediatric epilepsy surgery may be improved by the use of high-resolution neuroimaging and invasive electrographic studies, a more aggressive resection should be considered in certain patients, including hemispherectomy if a hemispheric epilepsy syndrome is suspected. Family counseling regarding treatment expectations is critical, and reoperation may be warranted in select cases. PMID- 25127101 TI - Discovery of furan-2-carbohydrazides as orally active glucagon receptor antagonists. AB - Furan-2-carbohydrazides were found as orally active glucagon receptor antagonists. Starting from the hit compound 5, we successfully determined the structure activity relationships of a series of derivatives obtained by modifying the acidity of the phenol. We identified the ortho-nitrophenol as a good scaffold for glucagon receptor inhibitory activity. Our efforts have led to the discovery of compound 7l as a potent glucagon receptor antagonist with good bioavailability and satisfactory long half-life. PMID- 25127102 TI - Development of chiral praziquantel analogues as potential drug candidates with activity to juvenile Schistosoma japonicum. AB - A series of chiral praziquantel analogues were synthesized and evaluated against Schistosoma japonicum both in vitro and in vivo. All compounds exhibited low to considerable good activity in vivo. Remarkably, worm reduction rate of R-3 was 60.0% at a single oral dose of 200mg/kg against juvenile stage of Schistosoma japonicum. The target compounds displayed in vivo antischistosomal activity against both Schistosoma japonicum and Schistosoma mansoni. Furthermore, all R isomers displayed stronger antischistosomal activity than S-isomers in vivo, indicating R-isomers were the active enantiomers, while S-isomers were less active ones. This structure activity relationship (SAR) could have important implications in further drug development for schistosomiasis. PMID- 25127104 TI - A new series of HAPs as anti-HBV agents targeting at capsid assembly. AB - A series of novel Heteroaryldihydropyrimidines (HAPs) derivatives were designed and synthesized as potent inhibitors of HBV capsid assembly. These compounds were prepared from efforts to optimize an earlier series of HAPs, and compounds Mo1, Mo7, Mo8, Mo10, Mo12, and Mo13 demonstrated potent inhibition of HBV DNA replication at submicromolar range. PMID- 25127103 TI - Structural studies provide clues for analog design of specific inhibitors of Cryptosporidium hominis thymidylate synthase-dihydrofolate reductase. AB - Cryptosporidium is the causative agent of a gastrointestinal disease, cryptosporidiosis, which is often fatal in immunocompromised individuals and children. Thymidylate synthase (TS) and dihydrofolate reductase (DHFR) are essential enzymes in the folate biosynthesis pathway and are well established as drug targets in cancer, bacterial infections, and malaria. Cryptosporidium hominis has a bifunctional thymidylate synthase and dihydrofolate reductase enzyme, compared to separate enzymes in the host. We evaluated lead compound 1 from a novel series of antifolates, 2-amino-4-oxo-5-substituted pyrrolo[2,3 d]pyrimidines as an inhibitor of Cryptosporidium hominis thymidylate synthase with selectivity over the human enzyme. Complementing the enzyme inhibition compound 1 also has anti-cryptosporidial activity in cell culture. A crystal structure with compound 1 bound to the TS active site is discussed in terms of several van der Waals, hydrophobic and hydrogen bond interactions with the protein residues and the substrate analog 5-fluorodeoxyuridine monophosphate (TS), cofactor NADPH and inhibitor methotrexate (DHFR). Another crystal structure in complex with compound 1 bound in both the TS and DHFR active sites is also reported here. The crystal structures provide clues for analog design and for the design of ChTS-DHFR specific inhibitors. PMID- 25127105 TI - Evaluation of the cyclopentane-1,2-dione as a potential bio-isostere of the carboxylic acid functional group. AB - Cycloalkylpolyones hold promise in drug design as carboxylic acid bio-isosteres. To investigate cyclopentane-1,2-diones as potential surrogates of the carboxylic acid functional group, the acidity, tautomerism, and geometry of hydrogen bonding of representative compounds were evaluated. Prototypic derivatives of the known thromboxane A2 prostanoid (TP) receptor antagonist, 3-(3-(2-((4 chlorophenyl)sulfonamido)-ethyl)phenyl)propanoic acid, in which the carboxylic acid moiety is replaced by the cyclopentane-1,2-dione unit, were synthesized and evaluated as TP receptor antagonists. Cyclopentane-1,2-dione derivative 9 was found to be a potent TP receptor antagonist with an IC50 value comparable to that of the parent carboxylic acid. These results indicate that the cyclopentane-1,2 dione may be a potentially useful carboxylic acid bio-isostere. PMID- 25127107 TI - Trends in boxed warnings and withdrawals for novel therapeutic drugs, 1996 through 2012. PMID- 25127108 TI - Supportive care needs of cancer patients: A literature review. AB - OBJECTIVE: This review of the research literature explored the supportive care needs of cancer patients of varying ages and genders at varying stages of cancer treatment. METHOD: We conducted a search of online databases of peer-reviewed studies published in the English language between 2009 and 2014. RESULTS: This paper reviews research studies that explored the supportive care needs of cancer patients through focus groups, surveys, and interviews. The samples addressed varied in age, ethnicity, and gender. SIGNIFICANCE OF RESULTS: One major need identified was the requirement of informational support. Other essential needs included emotional, spiritual, and financial support. Supportive care can be administered in various ways-for example, by religious communities or caregivers as well as providers. However, healthcare providers must recognize the supportive care needs of their patients and incorporate effective resources and interventions into treatment plans. PMID- 25127106 TI - Polymorphisms in the TNFA and IL6 genes represent risk factors for autoimmune thyroid disease. AB - BACKGROUND: Autoimmune thyroid disease (AITD) comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD. METHODS: Polymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays. RESULTS: A significant association was found between the allele A in TNFA-308 G/A and Hashimoto's thyroiditis, both in the dominant (OR = 1.82, CI = 1.37-2.43, p-value = 4.4*10(-5)) and log-additive (OR = 1.64, CI = 1.28-2.10, p-value = 8.2*10(-5)) models. The allele C in IL6-174 G/C is also associated with Hashimoto's thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR = 1.28, CI = 1.06-1.54, p-value = 8.9*10(-3)). The group with Graves' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR = 1.85, CI = 1.19-2.87, p-value = 7.0*10(-3)) and log-additive (OR = 1.69, CI = 1.17-2.44, p-value = 6.6*10(-3)) models. The risk for Hashimoto's thyroiditis and Graves' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59). CONCLUSIONS: This study reports significant associations of genetic variants in TNFA and IL6 with the risk for AITD, highlighting the relevance of polymorphisms in inflammation-related genes in the etiopathogenesis of AITD. PMID- 25127109 TI - Trans-axillary approach for breast implant exchange in high risk cases of irradiated or attenuated skin. AB - BACKGROUND: Breast reconstruction with implants after tissue expansion is one of the most common methods of reconstruction. Although this approach is generally reliable, exchange of breast tissue expander for implant through the standard anterior incision presents a challenge in cases with attenuated soft tissue envelope due to radiation, thin anatomy, prior surgery, or combination of the above. We propose that a trans-axillary approach is a safe and alternate approach for implant exchange in the high-risk patients. TECHNIQUE AND CASE EXAMPLES: A case series of 16 patients with multiple risk factors for compromised soft tissue that underwent a trans-axillary approach for implant exchange is reported. The trans-axillary implant exchange technique involves use of a standard 4 cm axillary incision, removal of the expander, judicious capsulotomy, placement of permanent implant, and closure in three separate tissue layers. RESULTS: All trans-axillary cases were successful and all incisions were well healed without dehiscence, infection, or seroma. The average patient age was 49.4 years, and 50% of patients had received or were scheduled to receive radiation therapy. Nine patients underwent unilateral trans-axillary expander exchange while 7 patients were bilateral. Median implant size was 360 cc (mean 369 cc, range 150-600 cc), and mean follow-up for all patients was over 24 months. There were no cases of implant extrusion, capsular contracture requiring re-operation, or lymphedema. Six patients underwent concurrent or subsequent nipple reconstruction. CONCLUSIONS: This approach illustrates application of a technique commonly used in breast aesthetic augmentation to address a common reconstructive dilemma, which we believe to be a useful tool in prosthesis-based breast reconstruction, especially in patients with compromised soft tissue envelopes. PMID- 25127110 TI - Updated S2K AWMF guideline for the diagnosis and follow-up of obstructive sialadenitis--relevance for radiologic imaging. AB - The interdisciplinarily developed German S2k AWMF guideline for the treatment of obstructive sialadenitis represents a new standard in the guideline program of the AWMF, the German Society for Consultants and the clinical disciplines working in the field of diseases of the head and neck region. In the last few years new diagnostic and therapeutic possibilities have been established in obstructive chronic Sialadenitis offering individually optimized therapeutic strategies. Only a few years ago extirpation of the whole affected gland was the only relevant therapy option. Nowadays therapeutic options such as interventional sialendoscopy and extracorporeal shock-wave lithotripsy (ESWL) are available in combination with marsupialization or incision of the duct. If possible the focus is on preserving the main glandular duct. In the following article the relevant aspects for the diagnostic radiologic procedures are presented. PMID- 25127111 TI - [Diagnostic error: lung cancer]. PMID- 25127112 TI - Potential utility of a new ulcerative colitis segmental endoscopic index combining disease severity and the extent of inflammation. AB - GOAL: To investigate the potential utility of a new scoring system, the Ulcerative Colitis Segmental Endoscopic Index (UCSEI), which combines measures of disease severity and extent of inflammation. BACKGROUND: Intestinal mucosal healing (MH) is a new therapeutic goal for ulcerative colitis (UC). Discontinuous lesions are common in UC and endoscopic observation of the entire colon is important. STUDY: Patients with active mild-to-moderate UC received daily treatment with oral mesalazine (4 g/d) and mesalazine enemas (1 g/d) for 8 weeks. Endoscopic evaluations, using the UCSEI and Mayo Endoscopic Score (MES), were performed in 5 colonic segments at baseline and week 8. The UCSEI criteria included erythema, vascular pattern, friability, and erosion/ulcer. The sum of 5 subscores, determined for each segment, was calculated as the UCSEI. Disease activity was also assessed using the UC Disease Activity Index (UCDAI). MH was defined as MES=0 to 1. RESULTS: Of 58 patients, 51 completed the scheduled endoscopic evaluations. At week 8, the UCDAI score had significantly decreased from 6.63 (baseline) to 2.73 (P<0.001). The remission and MH rates were 35.3% and 55.3%, respectively. Segmental endoscopic evaluation, using UCSEI, showed that baseline inflammation tended to be more severe in the distal colon. The baseline UCSEI increased with the extent of disease, which was not seen in MES. Improvements in UCSEI were observed, even in the patients without decreases in the MES. CONCLUSIONS: UCSEI, reflecting disease severity and extent of inflammation, provides useful information for UC management that is not available with MES. PMID- 25127113 TI - Transjugular Intrahepatic Portosystemic Shunt for Acute Variceal Bleeding: A Meta analysis. AB - BACKGROUND AND AIMS: Acute variceal bleeding is the most common lethal complication of liver cirrhosis. A meta-analysis was conducted to compare the outcomes of transjugular intrahepatic portosystemic shunt (TIPS) to those of medical/endoscopic therapy for acute variceal bleeding in cirrhotic patients. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched for all relevant comparative studies. Odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI)were pooled for dichotomous and time-dependent variables, respectively. Subgroup analyses were performed according to the type of study design (randomized or nonrandomized studies), source of bleeding (esophageal or gastric varices), type of stent (covered or bare stent), and patient selection (high risk or unselected patients). RESULTS: Six papers were eligible. TIPS was superior to medical/endoscopic therapy in decreasing the incidence of treatment failure (OR=0.22; 95% CI, 0.11-0.44), improving overall survival (HR=0.55; 95% CI, 0.38-0.812), and decreasing the incidence of bleeding related death (OR=0.19; 95% CI, 0.06-0.59). Although TIPS did not significantly decrease the incidence of rebleeding (OR=0.27; 95% CI, 0.06-1.29), it became significantly greater in the subgroup meta-analyses of randomized studies (OR=0.09; 95% CI, 0.03-0.32) than in those of nonrandomized studies (OR=0.76; 95% CI, 0.40-1.45; subgroup difference, P=0.003), and in the subgroup meta-analyses of studies including high-risk patients (OR=0.06; 95% CI, 0.01-0.23) than in those including low-risk patients (OR=0.83; 95% CI, 0.44-1.56; subgroup difference, P=0.0007). In addition, TIPS did not significantly increase the incidence of posttreatment hepatic encephalopathy (OR=1.37; 95% CI, 0.63-2.99). CONCLUSIONS: With the exception of the benefit of prevention from treatment failure, TIPS with covered stents might improve the overall survival of high-risk patients with acute variceal bleeding. PMID- 25127114 TI - Long-term Outcomes of Symptomatic Gallbladder Sludge. AB - GOALS AND BACKGROUND: Long-term outcomes of symptomatic gallbladder (GB) sludge are not fully established. This study aimed to determine whether patients with symptomatic GB sludge could experience subsequent biliary events. STUDY: This study investigated consecutive patients who presented with typical biliary pain and underwent abdominal ultrasonography from March 2003 to December 2012. A prospectively maintained database of these patients, excluding those with gallstones, was reviewed retrospectively. We compared the development of biliary events such as acute cholecystitis, acute cholangitis, and acute pancreatitis between both GB sludge and non-GB sludge cohorts. RESULTS: In all, 58 and 70 patients were diagnosed with and without GB sludge, respectively. The 5-year cumulative biliary event rate was significantly higher in the GB sludge (33.9% vs. 15.8%, P=0.021) and the hazard ratio of subsequent biliary events was 2.573 (95% confidence interval, 1.124-5.889; P=0.025) in patients with GB sludge. The 5 year cumulative rate of each biliary event was higher in the GB sludge cohort (15.6% vs. 5.3% in acute cholecystitis, 15.5% vs. 5.3% in acute cholangitis, 18.4% vs. 11.1% in acute pancreatitis, respectively), although it was not statistically significant. Among the GB sludge cohort, subsequent biliary events were less frequent in patients who underwent cholecystectomy compared with those who did not (2/16, 12.5% vs. 17/42, 40.4%; P=0.067). CONCLUSIONS: GB sludge accompanying typical biliary pain can cause subsequent biliary events and cholecystectomy may prevent subsequent biliary events. Therefore, GB sludge would be considered as a culprit of biliary events. PMID- 25127115 TI - Rate of Recurrent Luminal Esophageal Cancer in Asymptomatic Patients After Curative Treatment for Esophageal Cancer. AB - GOALS: The goal of this study was to determine the luminal recurrence rate of asymptomatic patients undergoing annual surveillance esophagogastroduodenoscopy (EGD). BACKGROUND: Current guidelines recommend surveillance EGD in postesophagectomy patients with esophageal cancer if there is clinical suspicion of local recurrence. However, many patients undergo annual surveillance EGD despite the recommendations to the contrary. STUDY: A query was performed of all patients who underwent esophagectomy between January 2000 and April 2010 at Moffitt Cancer Center. Patients were included if: they underwent esophagectomy with curative intent, had at least 12 months of follow-up after surgery, and had a R0 resection. Clinical and pathologic data in patients with and without recurrent disease were compared using the Fisher exact tests. Mean differences were examined using the Wilcoxon rank sum test. RESULTS: 346 patients were included with a mean age of 63.5+/-10.4 years and mean follow-up of 40.9+/-24.8 months. Recurrence was detected in 89 (25.7%) patients at a mean follow-up of 17.9+/-15.9 months after surgery. Seventeen (19.1%) patients had recurrence involving the esophagus but 7 (7.9%) patients had associated regional or distant metastases. Nine patients had abnormal signs/symptoms prompting evaluation with EGD. One patient had isolated luminal recurrence. CONCLUSIONS: In this study the majority of patients recurred in the metastatic setting. One (0.29%) patient had localized recurrence; however, it was unclear if this patient had any symptoms or signs to prompt evaluation. Our results support the current recommendation of a symptom-base endoscopic evaluation for esophageal cancer recurrence. PMID- 25127117 TI - Outcome of pregnancy following second- or third-trimester intrauterine fetal death. AB - OBJECTIVE: To investigate the outcomes of a pregnancy after a second- or third trimester intrauterine fetal death (IUFD). METHODS: A prospective observational study was conducted at Trousseau Hospital (Paris, France) between 1996 and 2011. The first ongoing pregnancy in women who had had a previous IUFD was monitored. Management of their treatment was according to a standardized protocol. Recurrence of fetal death was the main outcome criterion. RESULTS: The subsequent pregnancies of 87 women who had experienced at least one previous IUFD were followed up. The cause of previous IUFD was placental in 50 (57%) women, unknown in 19 (22%), adnexal in 12 (14%), metabolic in 2 (2%), and malformative in 4 (5%). Three (3%) participants had another stillbirth. Overall, obstetric complications occurred in 34 (39%) pregnancies (including 22 [25%] preterm births, 5 [6%] small for gestational age, and 6 [7%] maternal vascular complications). Obstetric complications were significantly more common among women whose previous stillbirth had been due to placental causes than among those affected by other causes (P=0.02). CONCLUSION: Most pregnancies after IUFD resulted in a live birth; however, adverse obstetric outcomes were more common when the previous stillbirth was due to placental causes. PMID- 25127116 TI - Metformin protects cardiomyocyte from doxorubicin induced cytotoxicity through an AMP-activated protein kinase dependent signaling pathway: an in vitro study. AB - Doxorubicin (Dox) is one of the most widely used antitumor drugs, but its cumulative cardiotoxicity have been major concerns in cancer therapeutic practice for decades. Recent studies established that metformin (Met), an oral anti diabetic drug, provides protective effects in Dox-induced cardiotoxicity. Met has been shown to increase fatty acid oxidation, an effect mediated by AMP activated protein kinase (AMPK). Here we delineate the intracellular signaling factors involved in Met mediated protection against Dox-induced cardiotoxicity in the H9c2 cardiomyoblast cell line. Treatment with low dose Met (0.1 mM) increased cell viabilities and Ki-67 expressions while decreasing LDH leakages, ROS generations and [Ca2+]i. The protective effect was reversed by a co-treatment with compound-C, an AMPK specific inhibitor, or by an over expression of a dominant-negative AMPKalpha cDNA. Inhibition of PKA with H89 or a suppression of Src kinase by a small hairpin siRNA also abrogated the protective effect of the low dose Met. Whereas, with a higher dose of Met (1.0 mM), the protective effects were abolished regardless of the enhanced AMPK, PKA/CREB1 and Src kinase activity. In high dose Met treated cells, expression of platelet-derived growth factor receptor (PDGFR) was significantly suppressed. Furthermore, the protective effect of low dose Met was totally reversed by co-treatment with AG1296, a PDGFR specific antagonist. These data provide in vitro evidence supporting a signaling cascade by which low dose Met exerts protective effects against Dox via sequential involvement of AMPK, PKA/CREB1, Src and PDGFR. Whereas high dose Met reverses the effect by suppressing PDGFR expression. PMID- 25127118 TI - Neuronal cellular responses to extremely low frequency electromagnetic field exposure: implications regarding oxidative stress and neurodegeneration. AB - Neurodegenerative diseases comprise both hereditary and sporadic conditions characterized by an identifying progressive nervous system dysfunction and distinctive neuopathophysiology. The majority are of non-familial etiology and hence environmental factors and lifestyle play key roles in their pathogenesis. The extensive use of and ever increasing worldwide demand for electricity has stimulated societal and scientific interest on the environmental exposure to low frequency electromagnetic fields (EMFs) on human health. Epidemiological studies suggest a positive association between 50/60-Hz power transmission fields and leukemia or lymphoma development. Consequent to the association between EMFs and induction of oxidative stress, concerns relating to development of neurodegenerative diseases, such as Alzheimer disease (AD), have been voiced as the brain consumes the greatest fraction of oxygen and is particularly vulnerable to oxidative stress. Exposure to extremely low frequency (ELF)-EMFs are reported to alter animal behavior and modulate biological variables, including gene expression, regulation of cell survival, promotion of cellular differentiation, and changes in cerebral blood flow in aged AD transgenic mice. Alterations in inflammatory responses have also been reported, but how these actions impact human health remains unknown. We hence evaluated the effects of an electromagnetic wave (magnetic field intensity 1 mT; frequency, 50-Hz) on a well characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF exposure elevated the expession of NOS and O2(-), which were countered by compensatory changes in antioxidant catylase (CAT) activity and enzymatic kinetic parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine gene expression were additionally evaluated and found rapidly modified. Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not as well counteracted and resulted in a decline in CAT activity and a rise in O2( ) levels. Together these studies support the further evaluation of ELF-EMF exposure in cellular and in vivo preclinical models to define mechanisms potentially impacted in humans. PMID- 25127119 TI - Oligosaccharide substrate preferences of human extracellular sulfatase Sulf2 using liquid chromatography-mass spectrometry based glycomics approaches. AB - Sulfs are extracellular endosulfatases that selectively remove the 6-O-sulfate groups from cell surface heparan sulfate (HS) chain. By altering the sulfation at these particular sites, Sulfs function to remodel HS chains. As a result of the remodeling activity, HSulf2 regulates a multitude of cell-signaling events that depend on interactions between proteins and HS. Previous efforts to characterize the substrate specificity of human Sulfs (HSulfs) focused on the analysis of HS disaccharides and synthetic repeating units. In this study, we characterized the substrate preferences of human HSulf2 using HS oligosaccharides with various lengths and sulfation degrees from several naturally occurring HS sources by applying liquid chromatography mass spectrometry based glycomics methods. The results showed that HSulf2 preferentially digests highly sulfated HS oligosaccharides with zero acetyl groups and this preference is length dependent. In terms of length of oligosaccharides, HSulf2 digestion induced more sulfation decrease on DP6 (DP: degree of polymerization) compared to DP2, DP4 and DP8. In addition, the HSulf2 preferentially digests the oligosaccharide domain located at the non-reducing end (NRE) of the HS and heparin chain. In addition, the HSulf2 digestion products were altered only for specific isomers. HSulf2 treated NRE oligosaccharides also showed greater decrease in cell proliferation than those from internal domains of the HS chain. After further chromatographic separation, we identified the three most preferred unsaturated hexasaccharide for HSulf2. PMID- 25127120 TI - Automated segmentation and quantification of white matter hyperintensities in acute ischemic stroke patients with cerebral infarction. AB - White matter hyperintensities (WMHs) of presumed vascular origin are common in ageing population, especially in patients with acute cerebral infarction and the volume has been reported to be associated with mental impairment and the risk of hemorrhage from antithrombotic agents. WMHs delineation can be computerized to minimize human bias. However, the presence of cerebral infarcts greatly degrades the accuracy of WMHs detection and thus limits the application of computerized delineation to patients with acute cerebral infarction. We propose a computer assisted segmentation method to depict WMHs in the presence of cerebral infarcts in combined T1-weighted, fluid attenuation inversion recovery, and diffusion weighted magnetic resonance imaging (MRI). The proposed method detects WMHs by empirical threshold and atlas information, with subtraction of white matter voxels affected by acute infarction. The method was derived using MRI from 25 hemispheres with WMHs only and 13 hemispheres with both WMHs and cerebral infarcts. Similarity index (SI) and correlation were utilized to assess the agreement between the new automated method and a gold standard visually guided semi-automated method done by an expert rater. The proposed WMHs segmentation approach produced average SI, sensitivity and specificity of 83.142+/-11.742, 84.154+/-16.086 and 99.988+/-0.029% with WMHs only and of 68.826+/-14.036, 74.381+/-18.473 and 99.956+/-0.054% with both WMHs and cerebral infarcts in the derivation cohort. The performance of the proposed method with an external validation cohort was also highly consistent with that of the experienced rater. PMID- 25127121 TI - Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation. AB - Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML) treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA). Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPbeta contributed to the poor differentiation state of leukemic cells induced by c-Myc over expression. Importantly, over-expression of C/EBPbeta could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPbeta. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPbeta in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy. PMID- 25127122 TI - Image-based three-dimensional conformal brachytherapy for medically inoperable endometrial carcinoma. AB - PURPOSE: Definitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer. We present our experience using image-based brachytherapy (BT). METHODS AND MATERIALS: Patients with medically inoperable clinical Stage I endometrial adenocarcinoma received definitive BT with or without external beam radiotherapy. High-dose-rate BT was delivered using MRI- or CT-based planning for each fraction. For patients with an MRI, gross tumor volume (GTV) was contoured although dose was still prescribed to the clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1 2 cm of vagina. Equivalent 2 Gy doses (EQD2) were calculated. RESULTS: Thirty eight patients were treated from 2007 to 2013, 20 receiving BT alone with a median dose of 37.5 Gy in five to six fractions. For combined therapy, median external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15 month median followup, the 2-year actuarial local control and overall survival were 90.6% and 94.4%. No Grade 2-5 late toxicities were observed. Mean CTV D90 EQD2 for BT alone and combined therapy was 48.6 +/- 5.6 and 72.4 +/- 6.0 Gy, whereas mean GTV D90 EQD2 was 172.3 +/- 59.6 and 138.0 +/- 64.6 Gy. CONCLUSIONS: Image-based BT is feasible for medically inoperable early stage endometrial cancer with excellent early results. Despite low CTV doses, high doses delivered to GTV with BT likely accounts for high local control. Endometrial cancer guidelines for image-based planning are needed to define target volumes based on risk with differential dose delivery. PMID- 25127123 TI - Permanent prostate brachytherapy with or without supplemental external beam radiotherapy as practiced in Japan: outcomes of 1300 patients. AB - PURPOSE: To report outcomes for men treated with iodine-125 ((125)I) prostate brachytherapy (BT) at a single institution in Japan. METHODS AND MATERIALS: Between 2003 and 2009, 1313 patients (median age, 68 years) with clinically localized prostate cancer were treated with (125)I BT. Median prostate-specific antigen level was 7.6 ng/mL (range, 1.1-43.3). T-stage was T1c in 60%, T2 in 39%, and T3 in 1% of patients. The Gleason score was <7, 7, and >7 in 49%, 45%, and 6% of patients, respectively. Neoadjuvant androgen deprivation therapy was used in 40% of patients and combined external beam radiotherapy of 45 Gy in 48% of patients. Postimplant dosimetry was performed after 30 days after implantation, with total doses converted to the biologically effective dose. Survival functions were calculated by the Kaplan-Meier method and Cox hazard model. RESULTS: Median followup was 67 months (range, 6-126). The 7-year biochemical freedom from failure for low-, intermediate-, and selected high-risk prostate cancers were 98%, 93%, and 81%, respectively (p < 0.001). Multivariate analysis identified the Gleason score, initial prostate-specific antigen level, positive biopsy rate, dose, and neoadjuvant androgen deprivation therapy as predictors for biochemical freedom from failure. The 7-year actuarial developing Grade 3+ genitourinary and gastrointestinal toxicity was 2% and 0.3%, respectively. Forty-four percent patients with normal baseline potency retained normal erectile function at 5 years. CONCLUSIONS: (125)I prostate BT is a highly effective treatment option for low-, intermediate-, and selected high-risk prostate cancers. Side effects were tolerable. An adequate dose may be required to achieve successful biochemical control. PMID- 25127124 TI - Development and implementation of a clinical needs assessment to support nursing and midwifery students with a disability in clinical practice: part 1. AB - Equality and disability legislation, coupled with increasing numbers of students with a disability, and inadequate supports in clinical practice, acted as catalysts to explore how best to support undergraduate nursing and midwifery students on clinical placements. Historically, higher education institutions provide reasonable accommodations for theoretical rather than clinical modules for practice placements. This paper describes the development and implementation of a Clinical Needs Assessment designed to identify the necessary supports or reasonable accommodations for nursing and midwifery students with a disability undertaking work placements in clinical practice. The existing literature, and consultation with an expert panel, revealed that needs assessments should be competency based and clearly identify the core skills or elements of practice that the student must attain to achieve proficiency and competence. The five Domains of Competence, advocated by An Bord Altranais, the Nursing and Midwifery Board of Ireland, formed the framework for the Clinical Needs Assessment. A panel of experts generated performance indicators to enable the identification of individualised reasonable accommodations for year 1 nursing and midwifery students in one Irish University. Development and implementation of the Clinical Needs Assessment promoted equality, inclusion and a level playing field for nursing and midwifery students with a disability in clinical practice. PMID- 25127127 TI - Reduction of hydrogen peroxide accumulation and toxicity by a catalase from Mycoplasma iowae. AB - Mycoplasma iowae is a well-established avian pathogen that can infect and damage many sites throughout the body. One potential mediator of cellular damage by mycoplasmas is the production of H2O2 via a glycerol catabolic pathway whose genes are widespread amongst many mycoplasma species. Previous sequencing of M. iowae serovar I strain 695 revealed the presence of not only genes for H2O2 production through glycerol catabolism but also the first documented mycoplasma gene for catalase, which degrades H2O2. To test the activity of M. iowae catalase in degrading H2O2, we studied catalase activity and H2O2 accumulation by both M. iowae serovar K strain DK-CPA, whose genome we sequenced, and strains of the H2O2 producing species Mycoplasma gallisepticum engineered to produce M. iowae catalase by transformation with the M. iowae putative catalase gene, katE. H2O2 mediated virulence by M. iowae serovar K and catalase-producing M. gallisepticum transformants were also analyzed using a Caenorhabditis elegans toxicity assay, which has never previously been used in conjunction with mycoplasmas. We found that M. iowae katE encodes an active catalase that, when expressed in M. gallisepticum, reduces both the amount of H2O2 produced and the amount of damage to C. elegans in the presence of glycerol. Therefore, the correlation between the presence of glycerol catabolism genes and the use of H2O2 as a virulence factor by mycoplasmas might not be absolute. PMID- 25127128 TI - Systemic RNAi delivery to the muscles of ROSA26 mice reduces lacZ expression. AB - RNAi has potential for therapeutically downregulating the expression of dominantly inherited genes in a variety of human genetic disorders. Here we used the ROSA26 mouse, which constitutively expresses the bacterial lacZ gene in tissues body wide, as a model to test the ability to downregulate gene expression in striated muscles. Recombinant adeno-associated viral vectors (rAAVs) were generated that express short hairpin RNAs (shRNAs) able to target the lacZ mRNA. Systemic delivery of these rAAV6 vectors led to a decrease of beta-galactosidase expression of 30-50-fold in the striated muscles of ROSA26 mice. However, high doses of vectors expressing 21 nucleotide shRNA sequences were associated with significant toxicity in both liver and cardiac muscle. This toxicity was reduced in cardiac muscle using lower vector doses. Furthermore, improved knockdown in the absence of toxicity was obtained by using a shorter (19 nucleotide) shRNA guide sequence. These results support the possibility of using rAAV vectors to deliver RNAi sequences systemically to treat dominantly inherited disorders of striated muscle. PMID- 25127126 TI - Smad4 regulates ureteral smooth muscle cell differentiation during mouse embryogenesis. AB - Proper formation of ureteral smooth muscle cells (SMCs) during embryogenesis is essential for ureter peristalsis that propels urine from the kidney to the bladder in mammals. Currently the molecular factors that regulate differentiation of ureteral mesenchymal cells into SMCs are incompletely understood. A recent study has reported that Smad4 deficiency reduces the number of ureteral SMCs. However, its precise role in the ureteral smooth muscle development remains largely unknown. Here, we used Tbx18:Cre knock-in mouse line to delete Smad4 to examine its requirement in the development of ureteral mesenchyme and SMC differentiation. We found that mice with specific deletion of Smad4 in Tbx18 expressing ureteral mesenchyme exhibited hydroureter and hydronephrosis at embryonic day (E) 16.5, and the mutant mesenchymal cells failed to differentiate into SMCs with increased apoptosis and decreased proliferation. Molecular markers for SMCs including alpha smooth muscle actin (alpha-SMA) and smooth muscle myosin heavy chain (SM-MHC) were absent in the mutant ureters. Moreover, disruption of Smad4 significantly reduced the expression of genes, including Sox9, Tbx18 and Myocardin associated with SMC differentiation. These findings suggest that Smad4 is essential for initiating the SMC differentiation program during ureter development. PMID- 25127129 TI - Graph-based inter-subject pattern analysis of FMRI data. AB - In brain imaging, solving learning problems in multi-subjects settings is difficult because of the differences that exist across individuals. Here we introduce a novel classification framework based on group-invariant graphical representations, allowing to overcome the inter-subject variability present in functional magnetic resonance imaging (fMRI) data and to perform multivariate pattern analysis across subjects. Our contribution is twofold: first, we propose an unsupervised representation learning scheme that encodes all relevant characteristics of distributed fMRI patterns into attributed graphs; second, we introduce a custom-designed graph kernel that exploits all these characteristics and makes it possible to perform supervised learning (here, classification) directly in graph space. The well-foundedness of our technique and the robustness of the performance to the parameter setting are demonstrated through inter subject classification experiments conducted on both artificial data and a real fMRI experiment aimed at characterizing local cortical representations. Our results show that our framework produces accurate inter-subject predictions and that it outperforms a wide range of state-of-the-art vector- and parcel-based classification methods. Moreover, the genericity of our method makes it is easily adaptable to a wide range of potential applications. The dataset used in this study and an implementation of our framework are available at http://dx.doi.org/10.6084/m9.figshare.1086317. PMID- 25127130 TI - An engineered factor Va prevents bleeding induced by anticoagulant wt activated protein C. AB - OBJECTIVE: An increased risk of bleeding is observed in patients receiving activated protein C (APC), which may be a limiting factor for the application of novel APC therapies. Since APC's therapeutic effects often require its cytoprotective activities on cells but not APC's anticoagulant activities, an agent that specifically antagonizes APC's anticoagulant effects but not its cytoprotective effects could provide an effective means to control concerns for risk of bleeding. We hypothesized that superFVa, an engineered activated FVa variant that restores hemostasis in hemophilia could reduce APC-induced bleeding. APPROACH AND RESULTS: SuperFVa was engineered with mutations of the APC cleavage sites (Arg506/306/679Gln) and a disulfide bond (Cys609-Cys1691) between the A2 and A3 domains, which augment its biological activity and cause high resistance to APC. SuperFVa normalized APC-prolonged clotting times and restored APC suppressed thrombin generation in human and murine plasma at concentrations where wild-type (wt) FVa did not show effects. Following intravenous injection of APC into BALB/c mice, addition to whole blood ex vivo of superFVa but not wt-FVa significantly normalized whole blood clotting. Blood loss following tail clip or liver laceration was significantly reduced when superFVa was administered intravenously to BALB/c mice prior to intravenous APC-treatment. Furthermore, superFVa abolished mortality (~50%) associated with excessive bleeding following liver laceration in mice treated with APC. CONCLUSIONS: Our results provide proof of concept that superFVa is effective in preventing APC-induced bleeding and may provide therapeutic benefits as a prohemostatic agent in various situations where bleeding is a serious risk. PMID- 25127131 TI - Birth weight reference percentiles for Chinese. AB - OBJECTIVE: To develop a reference of population-based gestational age-specific birth weight percentiles for contemporary Chinese. METHODS: Birth weight data was collected by the China National Population-based Birth Defects Surveillance System. A total of 1,105,214 live singleton births aged >=28 weeks of gestation without birth defects during 2006-2010 were included. The lambda-mu-sigma method was utilized to generate percentiles and curves. RESULTS: Gestational age specific birth weight percentiles for male and female infants were constructed separately. Significant differences were observed between the current reference and other references developed for Chinese or non-Chinese infants. CONCLUSION: There have been moderate increases in birth weight percentiles for Chinese infants of both sexes and most gestational ages since 1980s, suggesting the importance of utilizing an updated national reference for both clinical and research purposes. PMID- 25127132 TI - A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo. AB - OBJECTIVE: Oral squamous cell carcinoma (OSCC) is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885. METHODS: We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared. RESULTS: Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin. CONCLUSIONS: The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC. PMID- 25127133 TI - Dietary regimens modify early onset of obesity in mice haploinsufficient for Rai1. AB - Smith-Magenis syndrome is a complex genomic disorder in which a majority of individuals are obese by adolescence. While an interstitial deletion of chromosome 17p11.2 is the leading cause, mutation or deletion of the RAI1 gene alone results in most features of the disorder. Previous studies have shown that heterozygous knockout of Rai1 results in an obese phenotype in mice and that Smith-Magenis syndrome mouse models have a significantly reduced fecundity and an altered transmission pattern of the mutant Rai1 allele, complicating large, extended studies in these models. In this study, we show that breeding C57Bl/6J Rai1+/- mice with FVB/NJ to create F1 Rai1+/- offspring in a mixed genetic background ameliorates both fecundity and Rai1 allele transmission phenotypes. These findings suggest that the mixed background provides a more robust platform for breeding and larger phenotypic studies. We also characterized the effect of dietary intake on Rai1+/- mouse growth during adolescent and early adulthood developmental stages. Animals fed a high carbohydrate or a high fat diet gained weight at a significantly faster rate than their wild type littermates. Both high fat and high carbohydrate fed Rai1+/- mice also had an increase in body fat and altered fat distribution patterns. Interestingly, Rai1+/- mice fed different diets did not display altered fasting blood glucose levels. These results suggest that dietary regimens are extremely important for individuals with Smith-Magenis syndrome and that food high in fat and carbohydrates may exacerbate obesity outcomes. PMID- 25127134 TI - Modifying lipid rafts promotes regeneration and functional recovery. AB - Ideal strategies to ameliorate CNS damage should promote both neuronal survival and axon regeneration. The receptor Neogenin promotes neuronal apoptosis. Its ligand prevents death, but the resulting repulsive guidance molecule a (RGMa) Neogenin interaction also inhibits axonal growth, countering any prosurvival benefits. Here, we explore strategies to inhibit Neogenin, thus simultaneously enhancing survival and regeneration. We show that bone morphogenetic protein (BMP) and RGMa-dependent recruitment of Neogenin into lipid rafts requires an interaction between RGMa and Neogenin subdomains. RGMa or Neogenin peptides that prevent this interaction, BMP inhibition by Noggin, or reduction of membrane cholesterol all block Neogenin raft localization, promote axon outgrowth, and prevent neuronal apoptosis. Blocking Neogenin raft association influences axonal pathfinding, enhances survival in the developing CNS, and promotes survival and regeneration in the injured adult optic nerve and spinal cord. Moreover, lowering cholesterol disrupts rafts and restores locomotor function after spinal cord injury. These data reveal a unified strategy to promote both survival and regeneration in the CNS. PMID- 25127135 TI - Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome signaling response. AB - Inflammasome-mediated caspase-1 activation is involved in cell death and the secretion of the proinflammatory cytokine interleukin-1beta (IL-1beta). Although the dynamics of caspase-1 activation, IL-1beta secretion, and cell death have been examined with bulk assays in population-level studies, they remain poorly understood at the single-cell level. In this study, we conducted single-cell imaging using a genetic fluorescence resonance energy transfer sensor that detects caspase-1 activation. We determined that caspase-1 exhibits all-or-none (digital) activation at the single-cell level, with similar activation kinetics irrespective of the type of inflammasome or the intensity of the stimulus. Real time concurrent detection of caspase-1 activation and IL-1beta release demonstrated that dead macrophages containing activated caspase-1 release a local burst of IL-1beta in a digital manner, which identified these macrophages as the main source of IL-1beta within cell populations. Our results highlight the value of single-cell analysis in enhancing understanding of the inflammasome system and chronic inflammatory diseases. PMID- 25127136 TI - A pseudouridine residue in the spliceosome core is part of the filamentous growth program in yeast. AB - Although pseudouridine nucleobases are abundant in tRNAs, rRNAs, and small nuclear RNAs (snRNAs), they are not known to have physiologic roles in cell differentiation. We have identified a pseudouridine residue (Psi28) on spliceosomal U6 snRNA that is induced during filamentous growth of Saccharomyces cerevisiae. Pus1p catalyzes this modification and is upregulated during filamentation. Several U6 snRNA mutants are strongly pseudouridylated at Psi28. Remarkably, these U6 mutants activate pseudohyphal growth, dependent upon Pus1p, arguing that U6-Psi28 per se can initiate at least part of the filamentous growth program. We confirmed this by using a designer small nucleolar RNA (snoRNA) targeting U6-U28 pseudouridylation. Conversely, mutants that block U6-U28 pseudouridylation inhibit pseudohyphal growth. U6-U28 pseudouridylation changes the splicing efficiency of suboptimal introns; thus, Pus1p-dependent pseudouridylation of U6 snRNA contributes to the filamentation growth program. PMID- 25127137 TI - Gli3 repressor controls cell fates and cell adhesion for proper establishment of neurogenic niche. AB - Neural stem cells (NSCs) in the subventricular zone (SVZ) rely on environmental signals provided by the neurogenic niche for their proper function. However, little is known about the initial steps of niche establishment, as embryonic radial glia transition to postnatal NSCs. Here, we identify Gli3 repressor (Gli3R), a component of the Sonic hedgehog (Shh) pathway, as a critical factor controlling both cell-type specification and structural organization of the developing SVZ. We demonstrate that Gli3R expressed in radial glia temporally regulates gp130/STAT3 signaling at the transcriptional level to suppress glial characteristics in differentiating ependymal cells. In addition, Gli3R maintains the proper level of Numb in ependymal cells to allow localization of cell adhesion molecules such as vascular cell adhesion molecule (VCAM) and E-cadherin. Thus, our findings reveal a role for Gli3R as a mediator of niche establishment and provide insights into the conditions required for proper SVZ neurogenic niche formation. PMID- 25127138 TI - Costs and benefits of mutational robustness in RNA viruses. AB - The accumulation of mutations in RNA viruses is thought to facilitate rapid adaptation to changes in the environment. However, most mutations have deleterious effects on fitness, especially for viruses. Thus, tolerance to mutations should determine the nature and extent of genetic diversity that can be maintained in the population. Here, we combine population genetics theory, computer simulation, and experimental evolution to examine the advantages and disadvantages of tolerance to mutations, also known as mutational robustness. We find that mutational robustness increases neutral diversity and, as expected, can facilitate adaptation to a new environment. Surprisingly, under certain conditions, robustness may also be an impediment for viral adaptation, if a highly diverse population contains a large proportion of previously neutral mutations that are deleterious in the new environment. These findings may inform therapeutic strategies that cause extinction of otherwise robust viral populations. PMID- 25127140 TI - Global scaling down of excitatory postsynaptic responses in cerebellar Purkinje cells impairs developmental synapse elimination. AB - Synapse elimination is crucial for precise neural circuit formation during postnatal development. We examined how relative differences in synaptic strengths among competing inputs and/or absolute synaptic strengths contribute to climbing fiber (CF) to Purkinje cell (PC) synapse elimination in the cerebellum. We generated mice with PC-selective deletion of stargazin (TARP gamma-2), the major AMPA receptor auxiliary subunit in PCs (gamma-2 PC-KO mice). Whereas relative differences between "strong" and "weak" CF-mediated postsynaptic response are preserved, absolute strengths of CF inputs are scaled down globally in PCs of gamma-2 PC-KO mice. Although the early phase of CF elimination is normal, dendritic translocation of the strongest CF and the late phase of CF elimination that requires Ca(2+)-dependent activation of Arc/Arg3.1 in PCs are both impaired in gamma-2 PC-KO mice. We conclude that, although relative differences in CF synaptic inputs are initially essential, proper synaptic scaling is crucial for accomplishing CF synapse elimination. PMID- 25127139 TI - Oncogene mimicry as a mechanism of primary resistance to BRAF inhibitors. AB - Despite the development of potent RAF/mitogen-activated protein kinase (MAPK) pathway inhibitors, only a fraction of BRAF-mutant patients benefit from treatment with these drugs. Using a combined chemogenomics and chemoproteomics approach, we identify drug-induced RAS-RAF-MEK complex formation in a subset of BRAF-mutant cancer cells characterized by primary resistance to vemurafenib. In these cells, autocrine interleukin-6 (IL-6) secretion may contribute to the primary resistance phenotype via induction of JAK/STAT3 and MAPK signaling. In a subset of cell lines, combined IL-6/MAPK inhibition is able to overcome primary resistance to BRAF-targeted therapy. Overall, we show that the signaling plasticity exerted by primary resistant BRAF-mutant cells is achieved by their ability to mimic signaling features of oncogenic RAS, a strategy that we term "oncogene mimicry." This model may guide future strategies for overcoming primary resistance observed in these tumors. PMID- 25127141 TI - Escape from telomere-driven crisis is DNA ligase III dependent. AB - Short dysfunctional telomeres are capable of fusion, generating dicentric chromosomes and initiating breakage-fusion-bridge cycles. Cells that escape the ensuing cellular crisis exhibit large-scale genomic rearrangements that drive clonal evolution and malignant progression. We demonstrate that there is an absolute requirement for fully functional DNA ligase III (LIG3), but not ligase IV (LIG4), to facilitate the escape from a telomere-driven crisis. LIG3- and LIG4 dependent alternative (A) and classical (C) nonhomologous end-joining (NHEJ) pathways were capable of mediating the fusion of short dysfunctional telomeres, both displaying characteristic patterns of microhomology and deletion. Cells that failed to escape crisis exhibited increased proportions of C-NHEJ-mediated interchromosomal fusions, whereas those that escaped displayed increased proportions of intrachromosomal fusions. We propose that the balance between inter- and intrachromosomal telomere fusions dictates the ability of human cells to escape crisis and is influenced by the relative activities of A- and C-NHEJ at short dysfunctional telomeres. PMID- 25127142 TI - Balanced activity of three mitotic motors is required for bipolar spindle assembly and chromosome segregation. AB - Bipolar spindle assembly requires force to organize the microtubule network. Here, we show that three motor proteins, namely Eg5, Kif15, and dynein, act together to produce the right force balance in the spindle. Excessive inward force results in monopolar spindle formation, while excessive outward force generation results in unstable spindles with splayed spindle poles. Blocking activity of all three motors prevents bipolar spindle formation, but established bipolar spindles are refractory to loss of all motor activity. Further analysis shows that although these preformed spindles remain bipolar, outward force generation is required to establish sufficient tension on kinetochores and to accomplish successful chromosome segregation. Together, these results show how Eg5, Kif15, and dynein work together to build a bipolar spindle and reveal an important role for antagonistic motors in chromosome segregation. PMID- 25127144 TI - Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental area dopamine neurons. AB - Distinct midbrain dopamine (mDA) neuron subtypes are found in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA), but it is mainly SNc neurons that degenerate in Parkinson's disease. Interest in how mDA neurons develop has been stimulated by the potential use of stem cells in therapy or disease modeling. However, very little is known about how specific dopaminergic subtypes are generated. Here, we show that the expression profiles of the transcription factors Sox6, Otx2, and Nolz1 define subpopulations of mDA neurons already at the neural progenitor cell stage. After cell-cycle exit, Sox6 selectively localizes to SNc neurons, while Otx2 and Nolz1 are expressed in a subset of VTA neurons. Importantly, Sox6 ablation leads to decreased expression of SNc markers and a corresponding increase in VTA markers, while Otx2 ablation has the opposite effect. Moreover, deletion of Sox6 affects striatal innervation and dopamine levels. We also find reduced Sox6 levels in Parkinson's disease patients. These findings identify Sox6 as a determinant of SNc neuron development and should facilitate the engineering of relevant mDA neurons for cell therapy and disease modeling. PMID- 25127145 TI - Sex-dependent gene expression in human pluripotent stem cells. AB - Males and females have a variety of sexually dimorphic traits, most of which result from hormonal differences. However, differences between male and female embryos initiate very early in development, before hormonal influence begins, suggesting the presence of genetically driven sexual dimorphisms. By comparing the gene expression profiles of male and X-inactivated female human pluripotent stem cells, we detected Y-chromosome-driven effects. We discovered that the sex determining gene SRY is expressed in human male pluripotent stem cells and is induced by reprogramming. In addition, we detected more than 200 differentially expressed autosomal genes in male and female embryonic stem cells. Some of these genes are involved in steroid metabolism pathways and lead to sex-dependent differentiation in response to the estrogen precursor estrone. Thus, we propose that the presence of the Y chromosome and specifically SRY may drive sex-specific differences in the growth and differentiation of pluripotent stem cells. PMID- 25127143 TI - Quantification of crypt and stem cell evolution in the normal and neoplastic human colon. AB - Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a "functional" stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC(-/+)). Furthermore, we show that, in adenomatous crypts (APC(-/-)), there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30-40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics. PMID- 25127146 TI - Creation of a computer self-efficacy measure: analysis of internal consistency, psychometric properties, and validity. AB - Computer self-efficacy is an often studied construct that has been shown to be related to an array of important individual outcomes. Unfortunately, existing measures of computer self-efficacy suffer from several deficiencies, including criterion contamination, outdated wording, and/or inadequate psychometric properties. For this reason, the current article presents the creation of a new computer self-efficacy measure. In Study 1, an over-representative item list is created and subsequently reduced through exploratory factor analysis to create an initial measure, and the discriminant validity of this initial measure is tested. In Study 2, the unidimensional factor structure of the initial measure is supported through confirmatory factor analysis and further reduced into a final, 12-item measure. In Study 3, the convergent and criterion validity of the 12-item measure is tested. Overall, this three study process demonstrates that the new computer self-efficacy measure has superb psychometric properties and internal reliability, and demonstrates excellent evidence for several aspects of validity. It is hoped that the 12-item computer self-efficacy measure will be utilized in future research on computer self-efficacy, which is discussed in the current article. PMID- 25127147 TI - Triazolopyrimidine compounds containing first-row transition metals and their activity against the neglected infectious Chagas disease and leishmaniasis. AB - Leishmaniasis and Chagas disease remain a significant global problem. Current treatments have serious disadvantage due to cost, toxicity, long therapy duration and resistance. In the last years increasing interest has arisen in drug development to fight both diseases. Recently, metal-based drugs have revealed as promising drugs in a variety of therapeutic areas. Herein we describe six newly synthesized transition metal complexes with a bioactive molecule 5,7-dimethyl 1,2,4-triazolo[1,5-a]pyrimidine (dmtp). All of them have been characterized by X ray, spectroscopic and thermal methods. In vitro and in vivo studies (murine model) on the antiproliferative activity of these complexes against Leishmania spp. (Leishmania infantum, Leishmania braziliensis) and Trypanosoma cruzi have been carried out. Our results reveal a strong potential of three of the assayed compounds as antiparasitic agents against the above-mentioned infectious diseases. PMID- 25127148 TI - Some molecular targets for antihyperlipidemic drug research. AB - High levels of cholesterol and other lipid constituents are major risk factors in the development of atherosclerosis as well as diseases and disorders associated with it. Though, drugs of various categories acting through different mechanisms are available for antihyperlipidemic therapy, there are limitations associated with each of them, keeping the interest in discovery of newer and better antihyperlipidemic drugs alive. Identification and exploitation of novel molecular targets for discovery of new antihyperlipidemic drugs is an important area of research. Twenty such drug targets are elaborated herein, for their biochemical roles, structures, estimations, as well as, exploitation for new drug discovery research. Few recently discovered drugs are based on such molecular targets are also discussed. PMID- 25127149 TI - Synthesis and biological evaluation of 1alpha,25-dihydroxyvitamin D3 analogues with aromatic side chains attached at C-17. AB - Two new analogues of the steroid hormone 1alpha,25-dihydroxyvitamin D3 with aromatic side chains attached at C-17 were designed to investigate their effects on VDR, HL-60 cell differentiation and tumor cell proliferation. These analogues were prepared by the classical photochemical ring opening approach. After the protection of both the 1alpha- and 3beta-hydroxyl in 1alpha hydroxydehydroepiandrosterone with TBS groups, followed by bromination with NBS and debromination in the presence of gamma-collidine, the diene intermediate was obtained. Hydrazone formation followed by iodine oxidation gave a vinyl iodide. The aromatic side chain at C-17 was introduced via the Negishi coupling of the resulting intermediate with an in situ generated zinc reagent with the substituted aryl bromide (CD-side chain) in the presence of catalytic amount of Pd(PPh3)4. After the removal of the TBDMS and MOM protective groups, followed by UV irradiation and the subsequent thermal reaction, the 1alpha,25-(OH)2-D3 analogues with a substituted phenyl ring attached at C-17 to replace the C-20 and C-21 were prepared. In the VDR competitive binding assay, compounds 2 and 3 almost lost their binding ability, and were only 0.01% and 0.015% as potent as the 1alpha,25-dihydroxyvitamin D3. However, compounds 2 and 3 were as potent as 1alpha,25-(OH)2-D3 in inducing HL-60 cell differentiation at concentrations of 30, 100, 300, 1000 nM, respectively. Moreover, compounds 2 and 3 exhibited similar or better antiproliferative potency against MCF-7 human breast cancer cells, the IC50 values for analogues 2, 3 and the natural hormone were 7.08, 7.56, and 12.5 MUM, respectively. PMID- 25127150 TI - Synthesis and in vitro antitumor activity of new series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives. AB - New series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives were synthesized and characterized by analytical and spectrometrical methods (IR, HRMS, (1)H and (13)C NMR). Nineteen of the synthesized compounds were selected by the National Cancer Institute (NCI), USA, to be screened for their antitumor activity at a single dose (10 MUM) against a panel of 60 cancer cell lines. The most active compounds, 4, 6, 10, 14, 17 and 20 were selected for further evaluation at five dose level screening. Compounds 17 (GI50 = 0.44 MUM, TGI = 1.2 MUM and LC50 MG-MID = 6.6 MUM) and 4 (GI50 = 0.77 MUM, TGI = 2.08 MUM and LC50 MG MID = 11.74 MUM) were proved to be the most active members in this study. 3D and 2D pharmacophoric maps for the structural features of both compounds were studied. PMID- 25127151 TI - Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain: pharmacophore mapping from known antibacterial leads. AB - Bacterial DNA gyrase is a well-established and clinically validated target to develop novel antibacterial. Our effort was designated to search for synthetically better compounds with possibility of hit to lead development. With this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5 naphthyridin-2(1H)-one derivatives were designed by molecular hybridization strategy and synthesized following nine step reaction to yield activity in low nanomolar range and commendable antibacterial activities. Compound 1-(4 fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin 4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 MUM, and not cytotoxic at 50 MUM in eukaryotic cell line. PMID- 25127152 TI - Novel multi-targeting anthra[2,3-b]thiophene-5,10-diones with guanidine containing side chains: interaction with telomeric G-quadruplex, inhibition of telomerase and topoisomerase I and cytotoxic properties. AB - Novel generations of antitumor anthraquinones are expected to be advantageous over the conventional chemotherapeutic agents. Previous structure-activity relationship studies demonstrated an importance of the positively charged side chains conjugated to anthra[2,3-b]thiophene-5,10-dione scaffolds. Exploring a role of individual side chain moieties in binding to the duplex and G-quadruplex DNA, modulation of telomerase and topoisomerase I activities, intracellular accumulation and cytostatic potency, we herein analyzed a series of reported and newly synthesized guanidine-containing derivatives of anthra[2,3-b]thiophene-5,10 dione. We found that the number of cationic side chains (namely, two) is critical for a tight interaction with human telomeric G-quadruplex (TelQ). Along with a larger drug-TelQ association constant, the telomerase attenuation by anthrathiophenediones with two basic groups in the side chains was more pronounced than by the analogs bearing one basic group. For mono-guanidinated compounds the substituent with the amino group in the side chain provided better TelQ affinity than the methylamine residue. The intracellular uptake of the mono guanidino derivative with two side chains was >2-fold higher than the respective value for the bis(guanidino) derivative. This difference can explain a lower antiproliferative potency of bis(guanidine) containing compounds. Thus, the modifications of side chains of anthra[2,3-b]thiophene-5,10-dione differently modulated drug-target interactions and cellular effects. Nevertheless, the selected compound 11-(3-aminopropylamino)-4-(2-guanidinoethylamino)anthra[2,3 b]thiophene-5,10-dione 13 demonstrated a high affinity to TelQ and the ability to stabilize the quadruplex structure. These properties were paralleled by reasonable potency of 13 as a telomerase/topoisomerase I inhibitor and an antiproliferative agent. These results indicate that the structural elements of anthra[2,3-b]thiophene-5,10-dione derivatives can be balanced to yield a candidate for further preclinical study. PMID- 25127153 TI - Synthesis of genistein coupled with sugar derivatives and their inhibitory effect on nitric oxide production in macrophages. AB - The isoflavone genistein 1 and some derivatives modulate IL-12, TNF-alpha and NO production by macrophages and lung cancer cell lines, and improve the clinical signs of experimental autoimmune encephalomyelitis (EAE). Seven genistein derivatives connected at C-6 position of a sugar, such as d-glucose and d galactose, were synthesized. The ability to modulate macrophage response was evaluated, showing variable inhibition capacity of NO and TNF-alpha production in J774.A1 and RAW 264.7. Five of the seven compounds were non-cytotoxic; compound 8 was more effective to inhibit NO and TNF-alpha production, without affecting cell viability. PMID- 25127155 TI - A case of secondary syphilis demonstrating nephrotic syndrome and a solitary intrahepatic mass in a human immunodeficiency virus-1-infected patient. AB - A 37-year-old, human immunodeficiency virus-1-infected Japanese man was referred because of nephrotic syndrome following emergence of generalized skin rash. Serological tests for syphilis turned out to be positive within ten months of the referral. Abdominal echography incidentally revealed a solitary intrahepatic mass without a detectable blood flow in segment 7. The patient's signs and symptoms, as well as the intrahepatic mass, resolved promptly after administration of amoxicillin. We consider that, in the present case, secondary syphilis caused the nephrotic syndrome and the intrahepatic mass, both of which have rarely been reported to date. PMID- 25127154 TI - Novel thienopyrimidinones as mGluR1 antagonists. AB - There has been much attention to discover mGluR1 antagonists for treating various central nervous system diseases such as seizures and neuropathic pain. Thienopyrimidinone derivatives were designed, synthesized, and biologically evaluated against mGluR1. Among the synthesized compounds, 3-(4-methoxyphenyl)-7 (o-tolyl)thienopyrimidin-4-one 30 exhibited the most potent inhibitory activity with an IC50 value of 45 nM and good selectivity over mGluR5. Also, the selective mGluR1 antagonist 30 showed marginal hERG channel activity (IC50 = 9.87 MUM), good profiles to CYP isozymes, and a good pharmacokinetic profile. Overall, the compound 30 was identified as a selective mGluR1 antagonist with a good pharmacokinetic profile, which is probably devoid of cardiac side effect and drug drug interactions. Therefore, the compound 30 can be expected to be broadly used as mGluR1 antagonistic chemical probe in in vitro and in vivo study for investigating CNS diseases. PMID- 25127156 TI - Fulminant pseudomembranous colitis caused by Clostridium difficile PCR ribotype 027 in a healthy young woman in Japan. AB - In the past two decades, Clostridium difficile polymerase chain reaction ribotype 027 strain has rapidly emerged as the leading cause of antibiotic-associated colitis in North America and Europe; however, it has been reported only occasionally in Japan. We report a case of fulminant pseudomembranous colitis caused by this strain in a healthy young woman in Japan without any previous medical history. The strain isolated from our patient was susceptible to both gatifloxacin and moxifloxacin, thus representing a historic strain. The acquisition of fluoroquinolone resistance was reported as the important key genetic event linked to the virulence of this strain. It is noteworthy that the fluoroquinolone-susceptible 027 strain caused fulminant colitis in a healthy young woman in a non-endemic area. Our experience suggests that C. difficile PCR ribotype 027 has the potential virulence factors that are not associated with a fluoroquinolone resistance-conferring mutation. PMID- 25127157 TI - Sleep and exercise: a reciprocal issue? AB - Sleep and exercise influence each other through complex, bilateral interactions that involve multiple physiological and psychological pathways. Physical activity is usually considered as beneficial in aiding sleep although this link may be subject to multiple moderating factors such as sex, age, fitness level, sleep quality and the characteristics of the exercise (intensity, duration, time of day, environment). It is therefore vital to improve knowledge in fundamental physiology in order to understand the benefits of exercise on the quantity and quality of sleep in healthy subjects and patients. Conversely, sleep disturbances could also impair a person's cognitive performance or their capacity for exercise and increase the risk of exercise-induced injuries either during extreme and/or prolonged exercise or during team sports. This review aims to describe the reciprocal fundamental physiological effects linking sleep and exercise in order to improve the pertinent use of exercise in sleep medicine and prevent sleep disorders in sportsmen. PMID- 25127158 TI - Co-infection with 'Candidatus Neoehrlichia mikurensis' and Borrelia afzelii in an Ixodes ricinus tick that has bitten a human in Romania. AB - Despite the vast importance of ticks as disease vectors, the infectious agents transmitted by ticks are still incompletely known in many areas. Here, we report for the first time the detection of the bacterium 'Candidatus Neoehrlichia mikurensis' in Romania, in an Ixodes ricinus tick obtained from a human. Furthermore, the tick also had a co-infection with Borrelia afzelii. 'Candidatus Neoehrlichia mikurensis' is one of the most recent discoveries of a tick-borne agent, and has been found in human patients in several European countries as well as in China. PMID- 25127159 TI - Highly sensitive method for diagnosis of subclinical B. ovis infection. AB - Babesia ovis is a tick-transmitted protozoa parasite that infects small ruminants causing fever, anaemia, hemoglobinuria, anorexia and, in acute cases, death. Common in tropical and sub-tropical areas, the presence of this parasite in sheep herds has an economic impact on industry and therefore sensitive methods for the diagnosis and disease eradication are required. To achieve this goal, a semi nested PCR for B. ovis specific identification was developed and consequent reaction conditions and enzymes were optimized and tested with field samples. 300 blood samples from small ruminants and 39 ticks from Rhipicephalus genus were collected from different regions of Portugal. Afterwards, DNA extraction was performed and conventional and semi-nested PCR were accomplished for all samples. The results obtained from both methodologies were compared and the sensitivity was evaluated. Employing the semi-nested PCR it was possible to identify a higher number of positive cases among the evaluated samples than using the conventional PCR, namely 38/300 blood samples and 7/39 ticks. However, fragment amplification was only observed in 5 out of 300 blood samples and in none of the 39 ticks when a conventional PCR was employed. The validation of the results was achieved by sequencing the DNA fragments corresponding to the hypervariable v4 region of the 18S ribosomal RNA gene and performing an alignment with sequences already published on GenBank((r)). The ticks collected in this study belong to the Rhipicephalus genus, although other species could be involved as a vector in the Babesia spread. The diagnostic assay here described is presently the most effective and sensitive method for detection of B. ovis in field blood samples and ticks, enabling the detection up to 1 parasite into 10(9) erythrocytes. PMID- 25127160 TI - Studies of Anaplasma phagocytophilum in sheep experimentally infected with the human NY-18 isolate: characterization of tick feeding sites. AB - Anaplasma phagocytophilum, transmitted by ticks of the genus Ixodes, was first described in Scotland as the agent of tick-borne fever in sheep and more recently as the cause of human granulocytic anaplasmosis in the U.S. and Europe. We previously reported sheep as an experimental host for the human NY-18 isolate of A. phagocytophilum. While clinical signs were not observed and infected granulocytes were not seen in stained blood smears, these sheep served as a good host for infection of ticks. In this research we characterized tick feeding sites to better understand tick/host/pathogen interactions. Ixodes scapularis adults were allowed to feed for 2 and 4 days on experimentally infected sheep, after which biopsies were taken beneath tick feeding sites for histopathology, PCR and immunohistochemistry (IHC) studies. In addition, the expression of selected immune response genes was studied in blood and feeding site biopsies. While necrosis was too advanced in 4-day biopsies for accurate cell counts, higher numbers of eosinophils and neutrophils were found in 2-day biopsies from infected sheep as compared with the uninfected controls. An unexpected result was the documentation of higher dermal inflammation in infected sheep at sites without ticks. A. phagocytophilum infected granulocytes were localized by immunohistochemistry (IHC) in skin biopsies using rabbit antibodies against the recombinant A. phagocytophilum major surface protein 4 as the primary antibody for indirect peroxidase-anti-peroxidase and fluorescent antibody IHC. These infected cells are likely to be the source of infection for ticks. Sheep therefore served as good hosts for studying host/pathogen/tick interactions of this human strain of A. phagocytophilum, and provided a means of producing infected ticks for future studies on tick/pathogen developmental and transmission cycles. PMID- 25127161 TI - Occurrence of ticks and prevalence of Anaplasma phagocytophilum and Borrelia burgdorferi s.l. in three types of urban biotopes: forests, parks and cemeteries. AB - The aim of the present study was to compare different urban biotopes for the occurrence of ixodid tick species, for the population density of Ixodes ricinus and for the prevalence rates of two emerging, zoonotic pathogens. Altogether 2455 ticks were collected from the vegetation on 30 places (forests, parks, cemeteries) of Budapest, Hungary. I. ricinus and Haemaphysalis concinna were collected in all three biotope types, but Dermacentor reticulatus only in parks and forests, and D. marginatus only in a forest. Highest population density of I. ricinus was observed in neglected parts of cemeteries. In females of this tick species the prevalence rates of Anaplasma phagocytophilum and Borrelia burgdorferi s.l. were significantly lower in cemeteries, than in parks or forests. In conclusion, risks associated with the presence of ticks and tick borne pathogens may be high in a city, but this depends on biotope types, due to habitat-related differences in the vegetation, as well as in the availability of tick hosts and pathogen reservoirs. PMID- 25127162 TI - Aqueous two-phase (PEG4000/Na2SO4) extraction and characterization of an acid invertase from potato tuber (Solanum tuberosum). AB - Invertases are key metabolic enzymes that catalyze irreversible hydrolysis of sucrose into fructose and glucose. Plant invertases have essential roles in carbohydrate metabolism, plant development, and stress responses. To study their isolation and purification from potato, an attractive system useful for the separation of biological molecules, an aqueous two-phase system, was used. The influence of various system parameters such as type of phase-forming salts, polyethylene glycol (PEG) molecular mass, salt, and polymer concentration was investigated to obtain the highest recovery of enzyme. The PEG4000 (12.5%, w/w)/Na2SO4(15%, w/w) system was found to be ideal for partitioning invertase into the bottom salt-rich phase. The addition of 3% MnSO4 (w/w) at pH 5.0 increased the purity by 5.11-fold with the recovered activity of 197%. The Km and Vmax on sucrose were 3.95 mM and 0.143 U mL(-1) min(-1), respectively. Our data confirmed that the PEG4000/Na2SO4 aqueous two-phase system combined with the presence of MnSO4 offers a low-cost purification of invertase from readily available potato tuber in a single step. The biochemical characteristics of temperature and pH stability for potato invertase prepared from an ATPS make the enzyme a good candidate for its potential use in many research and industrial applications. PMID- 25127163 TI - Repurposing human PDE4 inhibitors for neglected tropical diseases: design, synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1 inhibitors. AB - A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4) inhibitor cilomilast (1) was undertaken in order to identify inhibitors of phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the parasite which causes African sleeping sickness, a neglected tropical disease that affects thousands each year, and TbrPDEB1 has been shown to be an essential target of therapeutic relevance. Noting that 1 is a weak inhibitor of TbrPDEB1, we report the design and synthesis of analogs of this compound, culminating in 12b, a sub micromolar inhibitor of TbrPDEB1 that shows modest inhibition of T. brucei proliferation. PMID- 25127164 TI - Rupestonic acids B-G, NO inhibitory sesquiterpenoids from Artemisia rupestris. AB - Six new guaiane sesquiterpenoids, rupestonic acids B-G (1-6), have been isolated from the whole plants of Artemisia rupestris together with six known compounds (7 12). The structures of the new isolates (1-6) were elucidated on the basis of extensive 1D and 2D NMR analysis, and the absolute configurations were established by electronic circular dichroism (ECD) in combination with density functional theory calculations. In in vitro bioassays, compounds 2 and 6 exhibited significant inhibitory effects on LPS-stimulated NO production in BV-2 microglial cells with IC50 values of 2.6 and 2.2 MUM, respectively. PMID- 25127166 TI - Cryptochinones from Cryptocarya chinensis act as farnesoid X receptor agonists. AB - Cryptochinones A-D are tetrahydroflavanones isolated from the leaves of Cryptocarya chinensis, an evergreen tree whose extracts are believed to have a variety of health benefits. The origin of their possible bioactivity is unclear. The farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that has been widely targeted for developing treatments for chronic liver disease and for hyperglycemia. We studied whether cryptochinones A-D, which are structurally similar to known FXR ligands, may act at this target. Indeed, in mammalian one hybrid and transient transfection reporter assays, cryptochinones A-D transactivated FXR to modulate promoter action including GAL4, SHP, CYP7A1, and PLTP promoters in dose-dependent manner, while they exhibited similar agonistic activity as chenodeoxycholic acid (CDCA), an endogenous FXR agonist. Through molecular modeling docking studies we evaluated their ability to bind to the FXR ligand binding pocket. Our results indicate that cryptochinones A-D can behave as FXR agonists. PMID- 25127165 TI - A new phenylpropanoid and an alkylglycoside from Piper retrofractum leaves with their antioxidant and alpha-glucosidase inhibitory activity. AB - Two new compounds, piperoside (1) and isoheptanol 2(S)-O-beta-D-xylopyranosyl (1 >6)-O-beta-D-glucopyranoside (11), along with 10 known compounds 3,4 dihydroxyallylbenzene (2), 1,2-di-O-beta-D-glucopyranosyl-4-allylbenzene (3), tachioside (4), benzyl-O-beta-D-glucopyranoside (5), icariside F2 (6), dihydrovomifoliol-3'-O-beta-D-glucopyranoside (7), isopropyl O-beta-D glucopyranoside (8), isopropyl primeveroside (9), n-butyl O-beta-D glucopyranoside (10), isoheptanol 2(S)-O-beta-D-apiofuranosyl-(1->6)-O-beta-D glucopyranoside (12), were isolated from the leaves of Piper retrofractum. Their structures were determined from 1D-NMR, 2D-NMR, and HR-ESI-MS spectral, a modified Mosher's method, and comparisons with previous reports. All of the isolated compounds showed modest alpha-glucosidase inhibitory (4.60+/-1.74% to 11.97+/-3.30%) and antioxidant activities under the tested conditions. PMID- 25127167 TI - New class of methyl tetrazole based hybrid of (Z)-5-benzylidene-2-(piperazin-1 yl)thiazol-4(%H)-one as potent antitubercular agents. AB - In search of potential therapeutics for tuberculosis, we describe here the synthesis and in vitro antitubercular activity of a novel series of thiazolone piperazine tetrazole derivatives. Among all the synthesized derivatives, four compounds (10, 14, 20 and 33) exhibited more potent activity (MIC=3.08, 3.01, 2.62 and 2.51 MUM) than ethambutol (MIC=9.78 MUM) and pyrazinamide (MIC=101.53 MUM) against Mycobacterium tuberculosis. Furthermore, they displayed no toxicity against Vero cells (C1008) and mouse bone marrow derived macrophages (MBMDMphi). These investigated analogues have emerged as possible lead molecule to enlarge the scope of the study. PMID- 25127168 TI - Comparison of saponin composition and content in wild soybean (Glycine soja Sieb. and Zucc.) before and after germination. AB - Eight wild soybean accessions with different saponin phenotypes were used to examine saponin composition and relative saponin quantity in various tissues of mature seeds and two-week-old seedlings by LC-PDA/MS/MS. Saponin composition and content were varied according to tissues and accessions. The average total saponin concentration in 1 g mature dry seeds of wild soybean was 16.08 +/- 3.13 MUmol. In two-week-old seedlings, produced from 1 g mature seeds, it was 27.94 +/ 6.52 MUmol. Group A saponins were highly concentrated in seed hypocotyl (4.04 +/ 0.71 MUmol). High concentration of DDMP saponins (7.37 +/- 5.22 MUmol) and Sg-6 saponins (2.19 +/- 0.59 MUmol) was found in cotyledonary leaf. In seedlings, the amounts of group A and Sg-6 saponins reduced 2.3- and 1.3-folds, respectively, while DDMP + B + E saponins increased 2.5-fold than those of mature seeds. Our findings show that the group A and Sg-6 saponins in mature seeds were degraded and/or translocated by germination whereas DDMP saponins were newly synthesized. PMID- 25127169 TI - Biochemical characterization of two thermostable xylanolytic enzymes encoded by a gene cluster of Caldicellulosiruptor owensensis. AB - The xylanolytic extremely thermophilic bacterium Caldicellulosiruptor owensensis provides a promising platform for xylan utilization. In the present study, two novel xylanolytic enzymes, GH10 endo-beta-1,4-xylanase (Coxyn A) and GH39 beta 1,4-xylosidase (Coxyl A) encoded in one gene cluster of C.owensensis were heterogeneously expressed and biochemically characterized. The optimum temperature of the two xylanlytic enzymes was 75 degrees C, and the respective optimum pH for Coxyn A and Coxyl A was 7.0 and 5.0. The difference of Coxyn A and Coxyl A in solution was existing as monomer and homodimer respectively, it was also observed in predicted secondary structure. Under optimum condition, the catalytic efficiency (kcat/Km) of Coxyn A was 366 mg ml(-1) s(-1) on beechwood xylan, and the catalytic efficiency (kcat/Km) of Coxyl A was 2253 mM(-1) s(-1) on pNP-beta-D-xylopyranoside. Coxyn A degraded xylan to oligosaccharides, which were converted to monomer by Coxyl A. The two intracellular enzymes might be responsible for xylooligosaccharides utilization in C.owensensis, also provide a potential way for xylan degradation in vitro. PMID- 25127170 TI - Glycemic effect of oat and barley beta-glucan when incorporated into a snack bar: a dose escalation study. AB - BACKGROUND: The blood glucose-lowering effects of beta-glucan from oats and barley depend on the amounts consumed and their rheological properties. This has been recently challenged with growing evidence that the food matrix may also be an important factor in predicting its physiological response. OBJECTIVE: The objective of this study was to examine the effects of varying doses of beta glucan from oats and barley and added to a snack bar on postprandial glycemia. DESIGN: In a randomized crossover study, 12 healthy males and females consumed one of 8 snack bars containing 0 (control), 1.5, 3, and 6 g of beta-glucan derived from oats or barley or 3 white bread controls. All treatments contained 50 g of available carbohydrate. Blood glucose concentrations were measured after ingestion of the treatments over 2 hours. RESULTS: Incorporation of 1.5 to 6 g of beta-glucan into snack bars had no additional glucose-lowering benefits irrespective of dose and source compared to the control bars (0 g beta-glucan), suggesting that both the solid food matrix and composition of the bars may play a role in their effects on glycemic response. All bars reduced blood glucose area under the curve (AUC) by an average of 25% (p < 0.05) compared to the mean of the 3 white bread controls. CONCLUSION: Adding beta-glucan from oats and barley to the snack bar formulation used in this study did not yield any additional benefits beyond the glucose-lowering effects of the snack bars themselves. PMID- 25127171 TI - Anti-CGRP antibodies: a new approach to migraine prevention. PMID- 25127172 TI - Epilepsy: lost in translation. PMID- 25127173 TI - Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene related peptide, for the prevention of migraine: a phase 2, randomised, double blind, placebo-controlled study. AB - BACKGROUND: Migraine remains poorly treated, with few effective preventive drugs available. We assessed the safety and efficacy of LY2951742, a fully humanised monoclonal antibody to calcitonin gene-related peptide, for migraine prevention. METHODS: We did a randomised, double-blind, placebo-controlled, phase 2 proof-of concept study at 35 centres in the USA. Patients aged 18-65 years with four to 14 migraine headache days per month were randomly assigned (1:1) to LY2951742 or placebo by a computerised randomisation scheme. LY2951742 (150 mg) or placebo were given as a subcutaneous injection once every 2 weeks for 12 weeks. The primary endpoint was the mean change in number of migraine headache days per 28 day period assessed at 9-12 weeks. Safety was assessed over 24 weeks, including the 12-week treatment period and the subsequent 12 weeks after study drug administration. Patients and treating investigators were masked to treatment allocation. Analyses were by intention to treat. A mixed-effects model of repeated measures was used, including patient baseline value, treatment, visit, and treatment-by-visit interaction as fixed effects, and patients as random effects. Safety measures were analysed according to the treatment received. This study has been completed and is registered with ClinicalTrials.gov, NCT01625988. FINDINGS: Between July 31, 2012, and Sept 18, 2013, 218 patients were randomly assigned to LY2951742 (n=108, but one patient withdrew before treatment) or placebo (n=110). The mean change from baseline to week 12 in the number of migraine headache days was -4.2 (SD 3.1; 62.5% decrease) in the LY2951742 group compared with -3.0 (SD 3.0; 42.3% decrease) in the placebo group (least-squares mean difference -1.2, 90% CI -1.9 to -0.6; p=0.0030). Adverse events that occurred more frequently with LY2951742 than with placebo included injection site pain, erythema, or both (21 [20%] of 107 vs seven [6%] of 110), upper respiratory tract infections (18 [17%] vs ten [9%]), and abdominal pain (six [6%] vs three [3%]). There were two serious adverse events reported in the treatment arm and four in the placebo arm, none of which were deemed to be related to the study drug. INTERPRETATION: These results provide preliminary evidence that LY2951742 might be beneficial in migraine prevention and provide support for the role of calcitonin gene-related peptide in the pathogenesis of migraine. Further controlled studies are needed to assess the safety and efficacy of monoclonal calcitonin gene-related peptide antibodies for the preventive treatment of migraine. FUNDING: Arteaus Therapeutics. PMID- 25127175 TI - Atorvastatin induces T cell proliferation by a telomerase reverse transcriptase (TERT) mediated mechanism. AB - Statins are one of the most potent drugs in delaying age-related inflammatory changes in the arterial vessel wall, slowing down the progression of atherosclerosis. Statins have also been shown to abrogate telomere-attributed cardiovascular risk. The goal of our study was to explore a potential effect of atorvastatin on telomerase activity in peripheral blood mononuclear cells (PBMCs) and T-lymphocytes (T cells). METHODS AND RESULTS: Treatment with pharmacologically relevant concentrations (0.1-0.3 MUM) of atorvastatin resulted in a 6-fold increase of telomerase activity (TA) (p < 0.0001) in human and mouse PBMCs and CD4 T cells, translating into moderate proliferation of T lymphocytes. In contrast, high doses of atorvastatin (2-5 MUM) or the addition of LDL cholesterol completely inhibited proliferation, thereby abrogating telomerase activity. The proliferative effect of atorvastatin was ablated by the absense of the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT). Using transgenic GFP-mTert reporter mice, we observed a decrease in telomerase positive lymphocytes from 30% to 15% during the first 5 months of age (p < 0.01). This suggests that the decrease in immune cell turnover during normal development and maturation is mirrored by a reduction in telomerase activity in lymphocytes in-vivo. CONCLUSION: Atorvastatin and cholesterol have opposing effects on telomerase in mononuclear cells and T-lymphocytes. Our study suggests a link between cholesterol metabolism and telomere-related cardiovascular risk. PMID- 25127176 TI - Does "thinking about thinking" interfere with memory? An experimental memory study in obsessive-compulsive disorder. AB - Neuropsychological assessments of participants with obsessive-compulsive disorder (OCD) indicate impaired verbal memory if to be remembered material has to be organized. People with OCD also tend to focus their attention on their thoughts (heightened cognitive self-consciousness). We tested the hypothesis that cognitive self-consciousness causes verbal memory deficits by provoking a division of attention between study task and thoughts. Thirty-six participants with OCD, 36 matched healthy controls and 36 participants with major depressive disorder (MDD) learned under proactive interference in three study conditions: single-task condition, condition with heightened cognitive self-consciousness and condition with an external secondary task. Memory was impaired in the cognitive self-consciousness condition compared to both other conditions. Independent of condition, participants with OCD showed a reduced memory performance compared to healthy controls, but did not differ from participants with MDD. Our results are in line with the hypothesis that cognitive self-consciousness causes memory impairment. PMID- 25127174 TI - The challenge and promise of anti-epileptic therapy development in animal models. AB - Translation of successful target and compound validation studies into clinically effective therapies is a major challenge, with potential for costly clinical trial failures. This situation holds true for the epilepsies-complex diseases with different causes and symptoms. Although the availability of predictive animal models has led to the development of effective antiseizure therapies that are routinely used in clinical practice, showing that translation can be successful, several important unmet therapeutic needs still exist. Available treatments do not fully control seizures in a third of patients with epilepsy, and produce substantial side-effects. No treatment can prevent the development of epilepsy in at-risk patients or cure patients with epilepsy. And no specific treatment for epilepsy-associated comorbidities exists. To meet these demands, a redesign of translational approaches is urgently needed. PMID- 25127177 TI - Accelerate farmer's agricultural S&T training in Tibet. PMID- 25127179 TI - ACT Internet-based vs face-to-face? A randomized controlled trial of two ways to deliver Acceptance and Commitment Therapy for depressive symptoms: an 18-month follow-up. AB - The aim of the present study was to investigate two interventions based on Acceptance and Commitment Therapy (ACT) for depressive symptoms: A face-to-face treatment (ACT group) was compared to a guided self-help treatment delivered via the Internet consisting of two assessment sessions (pre and post) and an ACT based Internet program (iACT). Outpatients experiencing at least mild depressive symptoms were randomized to either approach. The iACT treatment group received access to an ACT-based Internet program and supportive web-based contact over a period of 6 weeks. The face-to-face group received ACT-based treatment once a week over the same period of time. In both groups, the results showed a significant effect on depression symptomatology, and general wellbeing after treatment and at the 18-month follow-up. However, the data indicated that the iACT group changed differently regarding depressive symptoms and wellbeing as compared to the face-to face ACT group. Results showed large pre-treatment to 18 month follow-up within-group effect sizes for all symptom measures in the iACT treatment group (1.59-2.08), and for most outcome measures in the face-to-face ACT group (1.12-1.37). This non-inferiority study provides evidence that guided Internet-delivered ACT intervention can be as effective as ACT-based face-to-face treatment for outpatients reporting depressive symptoms, and it may offer some advantages over a face-to-face intervention. PMID- 25127178 TI - Treatment of co-occurring PTSD-AUD: effects of exposure-based and non-trauma focused psychotherapy on alcohol and trauma cue-reactivity. AB - Laboratory studies have shown that exposure to trauma memories increases both craving and salivation responses to alcohol cues among individual with co occurring posttraumatic stress disorder (PTSD) and alcohol dependence (AD). The purpose of the present study was to examine 1) whether this cue reactivity is dampened following exposure-based treatment for PTSD and 2) how changes in reactivity to trauma cues correspond to changes in alcohol cue-reactivity. Adults with current PTSD and AD (N = 120) were randomly assigned to 9-12 sessions of either Trauma-focused Exposure Therapy (EXP) for PTSD or Health & Lifestyles (HLS, a non-trauma focused comparison treatment), concurrent with 6-week residential AD treatment-as-usual. Participants completed trauma and alcohol cue reactivity laboratory sessions before and after treatment. Compared to HLS, individuals receiving EXP showed significantly greater reductions in negative affect elicited by trauma cues following treatment. Both treatments demonstrated similar, moderate to large reductions in craving and salivary reactivity over time. Interestingly, latent change in trauma cue-elicited distress over the course of treatment predicted latent change in both trauma cue-elicited alcohol craving and salivation. Overall, findings highlight the utility of integrating trauma-focused therapies like EXP into substance use treatment in the interests of reducing PTSD symptoms and distress associated with trauma cues. PMID- 25127181 TI - Laser-induced nondestructive patterning of a thin ferroelectric polymer film with controlled crystals using Ge8Sb2Te11 alloy layer for nonvolatile memory. AB - We present a simple but robust nondestructive process for fabricating micropatterns of thin ferroelectric polymer films with controlled crystals. Our method is based on utilization of localized heat arising from thin Ge(8)Sb(2)Te(11) (GST) alloy layer upon exposure of 650 nm laser. The heat was generated on GST layer within a few hundred of nanosecond exposure and subsequently transferred to a thin poly(vinylidene fluoride-co-trifluoroethylene) film deposited on GST layer. By controlling exposure time and power of the scanned laser, ferroelectric patterns of one or two microns in size are fabricated with various shape. In the micropatterned regions, ferroelectric polymer crystals were efficiently controlled in both degree of the crystallinity and the molecular orientations. Nonvolatile memory devices with laser scanned ferroelectric polymer layers exhibited excellent device performance of large remnant polarization, ON/OFF current ratio and data retention. The results are comparable with devices containing ferroelectric films thermally annealed at least for 2 h, making our process extremely efficient for saving time. Furthermore, our approach can be conveniently combined with a number of other functional organic materials for the future electronic applications. PMID- 25127180 TI - Clinical application of inert gas Multiple Breath Washout in children and adolescents with asthma. AB - INTRODUCTION: Children with asthma often have normal spirometry despite significant disease. The pathology of the small airways in asthma may be assessed using Multiple Breath Washout (MBW) and calculating the Lung Clearance Index (LCI). There are only few studies using MBW in children with asthma and existing data regarding bronchodilator effect are contradictory. The aim of the present pilot study was to compare LCI in asthma and controls and assess the effect of salbutamol in children with asthma on the LCI. METHODS: Unselected patients with a diagnosis of asthma visiting the outpatient department of our hospital between 04-2010 and 03-2011 were recruited and compared to a healthy control group. MBW was performed as inert gas MBW using sulfurhexafluorid (SF6) as the tracer gas. Clinical data were documented and spirometry and MBW (EasyOne Pro, MBW module, NDD Switzerland) were performed before and after the use of salbutamol (200-400 MUg). Healthy controls performed baseline MBW only. RESULTS: 32 children diagnosed with asthma (4.7-17.4 years) and 42 controls (5.3-20.8) were included in the analysis. LCI differed between patients and controls, with a mean LCI (SD) of 6.48 (0.48) and 6.21 (0.38) (P = 0.008). Use of salbutamol had no significant effect on LCI for the group. CONCLUSION: These pilot data show that clinically stable asthma patients and controls both have a LCI in the normal range. However, in patients the LCI is significantly higher indicating that MBW may have a role in assessing small airways disease in asthma. PMID- 25127182 TI - Stormwater chemical contamination caused by cured-in-place pipe (CIPP) infrastructure rehabilitation activities. AB - Cured-in-place pipe (CIPP) is becoming a popular U.S. stormwater culvert rehabilitation method. Several State transportation agencies have reported that CIPP activities can release styrene into stormwater, but no other contaminants have been monitored. CIPP's stormwater contamination potential and that of its condensate waste was characterized. Condensate completely dissolved Daphnia magna within 24 h. Condensate pH was 6.2 and its chemical oxygen demand (COD) level was 36,000 ppm. D. magna mortality (100%) occurred in 48 h, even when condensate was diluted by a factor of 10,000 and styrene was present at a magnitude less than its LC50. Condensate and stormwater contained numerous carcinogenic solvents used in resin synthesis, endocrine disrupting contaminants such as plasticizers, and initiator degradation products. For 35 days, COD levels at the culvert outlets and downstream ranged from 100 to 375 ppm and styrene was 0.01 to 7.4 ppm. Although contaminant levels generally reduced with time, styrene levels were greatest 50 ft downstream, not at the culvert outlet. Cured CIPP extraction tests confirmed that numerous contaminants other than styrene were released into the environment and their persistence and toxicity should be investigated. More effective contaminant containment and cleaner installation processes must be developed to protect the environment. PMID- 25127183 TI - Challenges and opportunities in epigenetic drug discovery. PMID- 25127184 TI - Exploring the Concepts of Abstinence and Recovery Through the Experiences of Long Term Opiate Substitution Clients. AB - BACKGROUND: This study aimed to explore the client experience of long-term opiate substitution treatment (OST). METHODS: A qualitative grounded theory study set in a U.K. rural community drug treatment service. RESULTS: Continuous OST enabled stability and a sense of "normality." Participants expressed relief at moving away from previous chaotic lifestyles and freedom from the persistent fear of opiate withdrawal. However, for some, being on a script made them feel withdrawn, lethargic, and unable to fully participate in mainstream society. Intrapersonal barriers (motivation and fear) were perceived as key barriers to abstinence. CONCLUSIONS: Participants experienced long-term OST as a transition between illicit drug use and recovery. Recovery was seen as a process rather than a fixed goal, confirming that there is a need for services to negotiate individualized recovery goals, spanning harm minimization and abstinence-oriented treatment approaches. PMID- 25127185 TI - Hydrogen bonding, halogen bonding and lithium bonding: an atoms in molecules and natural bond orbital perspective towards conservation of total bond order, inter- and intra-molecular bonding. AB - One hundred complexes have been investigated exhibiting D-X...A interactions, where X = H, Cl or Li and DX is the 'X bond' donor and A is the acceptor. The optimized structures of all these complexes have been used to propose a generalized 'Legon-Millen rule' for the angular geometry in all these interactions. A detailed Atoms in Molecules (AIM) theoretical analysis confirms an important conclusion, known in the literature: there is a strong correlation between the electron density at the XA bond critical point (BCP) and the interaction energy for all these interactions. In addition, we show that extrapolation of the fitted line leads to the ionic bond for Li-bonding (electrostatic) while for hydrogen and chlorine bonding, it leads to the covalent bond. Further, we observe a strong correlation between the change in electron density at the D-X BCP and that at the X...A BCP, suggesting conservation of the bond order. The correlation found between penetration and electron density at BCP can be very useful for crystal structure analysis, which relies on arbitrary van der Waals radii for estimating penetration. Various criteria proposed for shared- and closed-shell interactions based on electron density topology have been tested for H/Cl/Li bonded complexes. Finally, using the natural bond orbital (NBO) analysis it is shown that the D-X bond weakens upon X bond formation, whether it is ionic (DLi) or covalent (DH/DCl) and the respective indices such as ionicity or covalent bond order decrease. Clearly, one can think of conservation of bond order that includes ionic and covalent contributions to both D-X and X...A bonds, for not only X = H/Cl/Li investigated here but also any atom involved in intermolecular bonding. PMID- 25127187 TI - Radiation stability of cations in ionic liquids. 5. Task-specific ionic liquids consisting of biocompatible cations and the puzzle of radiation hypersensitivity. AB - In 1953, an accidental discovery by Melvin Calvin and co-workers provided the first example of a solid (the alpha-polymorph of choline chloride) showing hypersensitivity to ionizing radiation: under certain conditions, the radiolytic yield of decomposition approached 5 * 10(4) per 100 eV (which is 4 orders of magnitude greater than usual values), suggesting an uncommonly efficient radiation-induced chain reaction. Twenty years later, the still-accepted mechanism for this rare condition was suggested by Martyn Symons, but no validation for this mechanism has been supplied. Meanwhile, ionic liquids and deep eutectic mixtures that are based on choline, betainium, and other derivitized natural amino compounds are presently finding an increasing number of applications as diluents in nuclear separations, where the constituent ions are exposed to ionizing radiation that is emitted by decaying radionuclides. Thus, the systems that are compositionally similar to radiation hypersensitive solids are being considered for use in high radiation fields, where this property is particularly undesirable! In Part 5 of this series on organic cations, we revisit the phenomenon of radiation hypersensitivity and explore mechanistic aspects of radiation-induced reactions involving this class of task-specific, biocompatible, functionalized cations, both in ionic liquids and in reference crystalline compounds. We demonstrate that Symons' mechanism needs certain revisions and rethinking, and suggest its modification. Our reconsideration suggests that there cannot be conditions leading to hypersensitivity in ionic liquids. PMID- 25127186 TI - Stereoconvergent arylations and alkenylations of unactivated alkyl electrophiles: catalytic enantioselective synthesis of secondary sulfonamides and sulfones. AB - The development of efficient methods for the generation of enantioenriched sulfonamides and sulfones is an important objective for fields such as organic synthesis and medicinal chemistry; however, there have been relatively few reports of direct catalytic asymmetric approaches to controlling the stereochemistry of the sulfur-bearing carbon of such targets. In this report, we describe nickel-catalyzed stereoconvergent Negishi arylations and alkenylations of racemic alpha-bromosulfonamides and -sulfones that furnish the desired cross coupling product in very good ee and yield for an array of reaction partners. Mechanistic studies are consistent with the generation of a radical intermediate that has a sufficient lifetime to diffuse out of the solvent cage and to cyclize onto a pendant olefin. PMID- 25127188 TI - Optical functional performance of the osteo-odonto-keratoprosthesis. AB - PURPOSE: The aim of this study was to evaluate optical and visual functional performance of the osteo-odonto-keratoprosthesis (OOKP). METHODS: Optical design and analysis was performed with customized optical design software. Nine patients with implanted OOKP devices and 9 age-matched control patients were assessed. Contrast sensitivity was assessed and glare effect was measured with a brightness acuity test. All OOKP patients underwent kinetic Goldmann perimetry and wavefront aberrometry and completed the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). RESULTS: Optical analysis showed that the optical cylinder is near diffraction-limited. A reduction in median visual acuity (VA) with increasing glare settings was observed from 0.04 logMAR (without glare) to 0.20 logMAR (with glare at "high" setting) and significantly reduced statistically when compared with the control group at all levels of glare (P < 0.05). Contrast sensitivity was significantly reduced when compared with age matched controls at medium and high spatial frequencies (P < 0.05). Median Goldmann perimetry was 65 degrees (interquartile range, 64-74 degrees; V-4e isopters) and 69 degrees excluding 2 glaucomatous subjects. Several vision related NEI VFQ-25 subscales correlated significantly with VA at various brightness acuity test levels and contrast sensitivity at medium spatial frequencies, including dependency, general vision, near activities and distance activities. CONCLUSIONS: The OOKP optical cylinder provides patients with a good level of VA that is significantly reduced by glare. We have shown in vivo that updates to the optical cylinder design have improved the patient's field of view. Reduction of glare and refinement of cylinder alignment methods may further improve visual function and patient satisfaction. PMID- 25127189 TI - New combined technique of deep intrastromal arcuate keratotomy overlayed by LASIK flap for treatment of high astigmatism. AB - PURPOSE: The aim of this study was to describe a novel technique combining deep intrastromal arcuate keratotomy and superficial lamellar keratotomy followed by excimer photoablation for the management of high naturally occurring or postkeratoplasty astigmatism. METHODS: In this retrospective case series, the first step was deep intrastromal arcuate keratotomy and superficial lamellar keratotomy performed at 100-MUm depth by femtosecond laser. Manual incisions were made for flap elevation. The second step, after 1 month, consisted of reopening the flap and using an excimer laser to correct residual ametropia. RESULTS: Nine eyes series were studied. The mean preoperative refractive cylinder correction was 6.11 +/- 2.54 diopters (D). The mean postoperative refractive cylinder correction was 2.85 +/- 1.31 D. The mean correction index was 1.07 +/- 0.28 D. The mean best-corrected visual acuity improved from 20/40 to 20/22 after the 2 steps. The median follow-up was 11 (range, 9-17) months. No complications were observed and postoperative outcome was satisfactory. CONCLUSIONS: Permitting correction of a broader range of high astigmatism with good accuracy, this combined approach minimizes excision of corneal stromal tissue and postoperative complications. PMID- 25127193 TI - Temperature-dependent phase transition and desorption free energy of sodium dodecyl sulfate at the water/vapor interface: approaches from molecular dynamics simulations. AB - Adsorption of surfactants at the water/vapor interface depends upon their chemical potential at the interface, which is generally temperature-dependent. Molecular dynamics simulations have been performed to reveal temperature influences on the microstructure of sodium dodecyl sulfate (SDS) molecule adsorption layer. At room temperature, SDS molecules aggregate at the interface, being in a liquid-expanded phase, whereas they tend to spread out and probably transit to a gaseous phase as the temperature increases to above 318 K. This phase transition has been confirmed by the temperature-dependent changes in two dimensional array, tilt angles, and immersion depths to the aqueous phase of SDS molecules. The aggregation of SDS molecules accompanies with larger immersion depths, more coordination of Na(+) ions, and less coordination of water. Desorption free energy profiles show that higher desorption free energy appears for SDS molecules at the aggregate state at low temperatures, but no energy barrier is observed. The shapes of desorption free energy profiles depend upon the distribution of SDS at the interface, which, in turn, is related to the phase state of SDS. Our study sheds light on the development of adsorption thermodynamics and kinetics theories. PMID- 25127194 TI - Anisotropic hyperelastic behavior of soft biological tissues. AB - Constitutive laws are fundamental to the studies of the mechanically dominated clinical interventions involving soft biological tissues which show a highly anisotropic hyperelastic mechanical properties. The purpose of this paper was to develop an improved constitutive law based on the Holzapfel-Gasser-Ogden's model: to replace the isotropic part with Gent constitutive law so as to model the noncollagenous matrix of the media due to its generality and capability to reproduce the Neo-Hookean model. This model is implemented into an in-house finite element program. A uniaxial tension test is considered to study the influence of material parameter J(m) in Gent model and beta which represents the angle between the collagen fibers and the circumferential direction. A simulation of an adventitial strip specimen under tension is performed to show the applicability of this constitutive law. PMID- 25127195 TI - Reduced levels of plasma kisspeptin during the antenatal booking visit are associated with increased risk of miscarriage. AB - CONTEXT: Kisspeptin is a recently identified hormone encoded by the KISS1 gene, playing a critical role in human reproduction. Plasma kisspeptin levels rise dramatically during normal pregnancy due to placental synthesis, which implicates it as a potential tool for assessing risks of pregnancy complications. No previous prospective study has investigated the association between plasma kisspeptin and risk of miscarriage. OBJECTIVE: The objective of the study was to determine whether a single plasma kisspeptin or serum human chorionic gonadotropin (hCG) measurement in asymptomatic women attending their booking antenatal visit is associated with miscarriage. DESIGN: This was a prospective cohort study. SETTING: The study was conducted at a tertiary obstetric center. PARTICIPANTS: A total of 993 asymptomatic pregnant women with a gestation of 6 weeks or longer attending routine antenatal booking visit were recruited between January 2010 and December 2012. MAIN OUTCOME MEASURES: Plasma kisspeptin and serum hCG were measured during the antenatal booking visit. Pregnancy outcome was recorded prospectively. RESULTS: Plasma kisspeptin correlated with gestation (r(2) = 0.57; P < .0001). Gestational age-corrected (multiples of median) plasma kisspeptin was 60.4% lower (P < .001), and multiples of median-hCG was 36.1% lower (P < .001) in women later diagnosed with miscarriage compared with women without miscarriage. Increased plasma kisspeptin was associated with reduced miscarriage risk, even after adjusting for age, body mass index, gestational age, smoking, and blood pressure [odds ratio 0.13 (95% confidence interval 0.08-0.22), P = .0001]. Kisspeptin had a higher diagnostic performance for miscarriage than hCG (receiver-operator characteristic-area under the curve 0.899 +/- 0.025 plasma kisspeptin; 0.775 +/- 0.040, serum hCG, P < .01 vs plasma kisspeptin). CONCLUSION: Our data suggest for the first time that a single plasma kisspeptin measurement taken during the antenatal booking visit provides a potential novel marker for identifying asymptomatic pregnant women at a gestation of 6 weeks or greater at increased risk of miscarriage. PMID- 25127197 TI - Drinking identity as a mediator of the relationship between drinking motives and weekly alcohol consumption among heavy drinking undergraduate students. AB - OBJECTIVES: The present study assessed relationships among social, coping, enhancement, and conformity drinking motives and weekly alcohol consumption by considering drinking identity as a mediator of this relationship. METHODS: Participants were 260 heavy drinking undergraduate students (81% female; Mage=23.45; SD=5.39) who completed a web-based survey. RESULTS: Consistent with expectations, findings revealed significant direct effects of motives on drinking identity for all four models. Further, significant direct effects emerged for drinking identity on weekly drinking. Results partially supported predictions that motives would have direct effects on drinks per week; total effects of motives on drinking emerged for all models but direct effects of motives on weekly drinking emerged for only enhancement motives. There were significant indirect effects of motives on weekly drinking through drinking identity for all four models. CONCLUSIONS: The findings supported the hypotheses that drinking identity would mediate the relationship between drinking motives and alcohol consumption. These examinations have practical utility and may inform development and implementation of interventions and programs targeting alcohol misuse among heavy drinking undergraduate students. PMID- 25127198 TI - From socially prescribed perfectionism to problematic use of internet communicative services: the mediating roles of perceived social support and the fear of negative evaluation. AB - BACKGROUND: The present study developed and tested a model that explains how people who believe that others have unrealistically high standards and exert pressure on them to be perfect (that is, people high in socially prescribed perfectionism) develop a problematic use of internet communicative services (GPIU). Following the perfectionism social disconnection model and previous evidence about the role that the online environment might play in the development of problematic internet use, low reported social support and the fear of negative evaluations in face to face interactions were hypothesized to mediate the association between socially prescribed perfectionism and GPIU. METHODS: A sample of 465 undergraduate students was recruited (240 F; mean age 21.91+2.23years), and the hypotheses were tested through structural equation modeling separately for men and women. RESULTS: Among men, the association between SPP and GPIU was fully mediated by the fear of being negatively evaluated and the perception of low social support. For women, we found a partially mediated model in which SPP affected GPIU indirectly through the fear of negative evaluations. The presence of a direct effect of SPP on GPIU was also found. Moreover, perceived social support was not found to be a significant mediator among women. CONCLUSIONS: The findings suggest that problematic use of internet communicative services might be, at least in part, a defensive response to extreme social evaluation pressures. PMID- 25127196 TI - The interactive effect of neighborhood peer cigarette use and 5HTTLPR genotype on individual cigarette use. AB - BACKGROUND: Previous cross-sectional research has shown that adolescents' cigarette use is interactively associated with that of their school peers and their 5HTTLPR genotype, such that the cigarette use of persons with more copies of the 5HTTLPR*S' allele is more dependent on school peers' cigarette use behaviors than their counterparts. This analysis seeks to extend this novel finding by examining whether the same conclusion can be reached when substituting neighborhood peers for school peers and examining the timing of the initiation of any and regular smoking in adolescence. METHODS: This analysis employs an independent sample with longitudinal measures of cigarette use among 6th through 8th graders clustered in 82 neighborhoods, of whom 1098 contributed genetic data. The proportion of respondents who had ever smoked cigarettes by the first wave was calculated for each census block group in the study. 5HTTLPR genotype was assayed using the method of Whisman et al. (2011). The timing of any or regular smoking initiation and over four years were modeled as dependent variables using Cox proportional hazard models. RESULTS: The interaction of neighborhood peer smoking behavior in the first wave and 5HTTLPR genotype statistically significantly predicted any smoking initiation (hazard ratio: 3.532; p value=0.002) and regular smoking initiation (hazard ratio: 5.686; p-value=0.000), net of controls for sex, race/ethnicity, grade in the first wave of data, and parental educational attainment. These findings reach the same conclusions as previous cross-sectional research. CONCLUSIONS: These results differ in the model of gene-environment interaction that they support. The findings for any smoking initiation are consistent with the diathesis-stress model of gene-environment interaction; the findings for regular smoking initiation are consistent with the differential susceptibility model. PMID- 25127199 TI - Revisiting the rationale for social normative interventions in student drinking in a UK population. AB - OBJECTIVES: Social normative re-education interventions are based on the premise that harmful student drinking is caused by misperceptions of campus drinking norms. They have become dominant despite little evidence for effectiveness, especially with heavy drinkers. The objective of this study was to explore the relative importance of social norms and other key cognitive constructs in predicting single occasion alcohol consumption in undergraduates. METHODS: DESIGN: A cross sectional survey design was utilised. SETTING: Three UK universities. PARTICIPANTS: 367 1st year undergraduate students. MEASURES: Frequency and quantity of alcohol consumed; hazardous drinking; descriptive and injunctive normative perceptions of alcohol consumption were measured at 3 proximal-distal levels. RESULTS: Participants in this study were drinking at much higher levels than previously reported (means of 20 units for males, 16 units for females on a single drinking occasion); 85% exceeded the UK government's definition of binge drinking of 8 units or more on a single occasion. Norm perceptions, which form the basis of social normative interventions, were not significant predictors of individual consumption. Cognitive appraisal of oneself as a drinker and volitional behavioural control on drinking occasions are the most important constructs in predicting heavy drinking in this sample of UK undergraduate students. The model that emerges explains 40% of the variance in single occasion consumption. CONCLUSIONS: Students are consuming levels of alcohol that will result in accumulative harm if unchecked. This study provides an explanation as to why social normative interventions are not effective. An alternative focus for reducing alcohol consumption in UK undergraduates is suggested. PMID- 25127200 TI - miR-29b suppresses proliferation, migration, and invasion of tongue squamous cell carcinoma through PTEN-AKT signaling pathway by targeting Sp1. AB - OBJECTIVES: miR-29b has been implicated in various cancers. However, the role of miR-29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the role of miR-29b in TSCC progression. MATERIALS AND METHODS: The expression of miR-29b was analyzed in TSCC tissues and cells. Functional studies were performed in TSCC cells. Real time-PCR, Western blot, cell proliferation, transwell, and dual luciferase reporter assays were performed according to standard procedures. RESULTS: miR-29b was significantly decreased in TSCC specimens and cell lines compared with corresponding normal counterparts. Overexpression of miR-29b significantly inhibited the proliferation, migration, invasion, and cell-cycle progression of TSCC cells, and promoted apoptosis. Moreover, miR-29b targeted the 3' untranslated region of the Sp1 transcript and resulted in the deregulation of Sp1. The inhibition of Sp1 by miR-29b subsequently resulted in the upregulation of PTEN, leading to a decline of phosphorylated AKT. Knockdown of Sp1 in TSCC cell lines mimicked the effects of miR-29b overexpression. In addition, the expression of miR-29b was inversely correlated with Sp1 and positively correlated with the PTEN in TSCC specimens. CONCLUSION: miR-29b functions as a tumor suppressor in TSCC, and the miR 29b/Sp1/PTEN/AKT axis might represent a potential therapeutic target for TSCC intervention. PMID- 25127202 TI - Direct synthesis of alpha-trifluoromethyl ketone from (hetero)arylacetylene: design, intermediate trapping, and mechanistic investigations. AB - Regioselective addition across the alkynes has been achieved in a silver catalyzed protocol utilizing Langlois reagent (CF3SO2Na) and molecular O2 to access medicinally active alpha-trifluoromethyl ketone compounds. This method was successful in producing alpha-trifluoromethyl ketone in heterocyclic scaffolds, which are incompatible with earlier strategies. Experimental findings suggest a mechanism involving alpha-styrenyl radical intermediate and 1-methyl-2 pyrrolidinone (NMP) solvent, which leads to crystallographically characterized N methylsuccinimide. Isotope labeling, kinetic studies, and intermediate trapping further helped to gain insight into this energy-demanding process. PMID- 25127201 TI - A systematic review of patient acceptance of screening for oral cancer outside of dental care settings. AB - This systematic review summarised the literature on patient acceptability of screening for oral cancer outside dental care settings. A comprehensive search of relevant literature was performed in EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, CINAHAL, psycINFO, CANCERLIT and BNI to identify relevant articles published between 1975 and Dec 2013. Studies reporting acceptability of oral cancer screening to undiagnosed individuals attending non-dental settings were eligible for inclusion. A total of 2935 references were initially identified from the computerised search but 2217 were excluded after screening the titles. From the abstracts of the remaining 178 articles, 47 full text articles were retrieved for further scrutiny, and 12 studies were found to be eligible for inclusion. In these studies, knowledge about oral cancer, anxiety related to the screening process, preference for care provision, and financial cost were influencing factors for the acceptance of screening. Written information provided to patients in primary care was reported to boost immediate knowledge levels of oral cancer, lessen anxiety, and increase intentions for screening. The majority of screening methods were entirely acceptable to patients; lack of acceptability from the patients' viewpoint was not a significant barrier to carrying out opportunistic screening of high-risk populations. In conclusion, the available evidence suggests that acceptance of, and satisfaction with oral cancer screening is high, particularly where patients have previously been educated about oral cancer. Further research focusing on patient's preferences would enable streamlining of the approach to oral cancer screening taken by any national programme. PMID- 25127203 TI - Analysis of CF...FC interactions on cyclohexane and naphthalene frameworks. AB - Intramolecular CF...FC interactions in selected organofluorine compounds (all-syn 1,2,3,4- and all-syn-1,2,4,5-tetrafluorocyclohexane, 1,8-difluoronaphthalene, 4,5 difluorophenanthrene, 2,2',5,5'-tetrafluorobiphenyl) were studied at the MP2/aug cc-pVDZ level using the recently developed noncovalent interaction (NCI) method. For the optimized minima, all CF...FC interactions that are identified by this method are classified as attractive, even in those cases where suitable isodesmic reaction energies fail to provide evidence for an energetic stabilization. Possible relations between these interactions and the observable JFF spin-spin coupling constant values are discussed. PMID- 25127204 TI - Pathways community HUB: a model for coordination of community health care. PMID- 25127206 TI - Care coordination, family-centered care, and functional ability in children with special health care needs in the United States. AB - The purpose of this study was to determine if there was an association between care coordination, family-centered care, and functional ability among children with special health care needs (CSHCN). Analysis of data from the 2005-2006 National Survey of CSHCN revealed that the percentages of CSHCN receiving care coordination and family-centered care were 59.3 and 66.3, respectively. Children who did not receive care coordination had a 53% higher adjusted odds (odds ratio=1.53, 95% confidence interval 1.21-1.94, P<0.001) for a limitation in functional ability compared to CSHCN who received care coordination. Family centered care was not associated with a limitation in functional ability in CSHCN (P=0.61). CSHCN are underserved with regard to care coordination and this appears to be associated with impaired functional ability. Longitudinal studies are needed to confirm causality. PMID- 25127205 TI - Failure to reach target glycated a1c levels among patients with diabetes who are adherent to their antidiabetic medication. AB - The objectives of this study were to describe patient characteristics and types of medications taken by those with poor glycemic control (A1c>7%) despite being adherent to antidiabetic medications. This is a retrospective analysis of administrative data from adult patients with diabetes enrolled in a large health plan in Hawaii (n=21,267 observations for 11,013 individuals) and adherent to their antidiabetic medications. Multivariable logistic regressions were estimated to determine characteristics and types of medications associated with poor glycemic control. Separate models were estimated to examine category of medication (insulin only, 1 oral medication, multiple oral medications, both oral medications and insulin) and specific therapeutic class of oral antidiabetic medications. Despite being adherent to their medications, 56.1% of patients had poor glycemic control. Compared to patients taking combination sulfonylureas, patients had a higher odds of having A1c>7% for all other oral diabetic medications, with odds ratios ranging from OR=2.07 for sulfonylureas alone to OR=1.33 for combination DPP-4 inhibitors. More than half of patients in this study had poor A1c control despite being adherent to their medications. This suggests that physicians, pharmacists, and other providers may need to monitor treatment regimens more carefully, encourage healthy behaviors, and intensify pharmacological treatment as needed. PMID- 25127207 TI - Ponesimod--a future oral therapy for psoriasis? PMID- 25127208 TI - Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double blind, placebo-controlled phase 2 trial. AB - BACKGROUND: We assessed the efficacy, safety, and tolerability of ponesimod, an oral, selective, reversible modulator of sphingosine 1-phosphate receptor 1, in patients with moderate to severe chronic plaque psoriasis. METHODS: Between Sept 22, 2010, and Oct 24, 2012, patients with psoriasis area and severity index (PASI) scores higher than 10 were enrolled into this multicentre double-blind, phase 2 study. They received 20 mg or 40 mg ponesimod or placebo once daily for 16 weeks. Those with at least 50% reduction in PASI score at 16 weeks and who were receiving ponesimod were rerandomised to receive maintenance ponesimod therapy or placebo until week 28. The primary endpoint was reduction in PASI score from baseline of at least 75% (PASI75) at week 16. This study is registered with ClinicalTrials.gov, number NCT01208090. FINDINGS: Of 326 patients initially randomised (20 mg ponesimod n=126, 40 mg ponesimod n=133, and placebo n=67) PASI75 was achieved at week 16 in 58 (46.0%), 64 (48.1%), and nine (13.4%), respectively. The treatment effect was significant for the two ponesimod doses (both p<0.0001). Of 219 patients who entered the maintenance period, PASI75 was achieved by week 28 in 35 (71.4%) of 49 who continued on 20 mg ponesimod and 41 (77.4%) of 53 on 40 mg ponesimod, and in 19 (42.2%) of 45 who swapped from 20 mg to placebo and 19 (40.4%) of 47 from 40 mg to placebo. Ponesimod was associated with dyspnoea, raised liver enzyme concentrations, and dizziness. INTERPRETATION: Significant clinical benefit was seen at week 16 that increased with maintenance therapy. FUNDING: Actelion Pharmaceuticals. PMID- 25127209 TI - Pretransfusion testing and transfusion of uncrossmatched erythrocytes. PMID- 25127210 TI - Lack of nephrotoxicity by 6% hydroxyethyl starch 130/0.4 during hip arthroplasty: a randomized controlled trial. AB - BACKGROUND: Hydroxyethyl starch (HES) is commonly used as plasma expander during surgery but may be nephrotoxic as seen in studies in patients with sepsis. The authors hypothesized that the possible nephrotoxicity of 6% HES 130/0.4 could be revealed by measurements of urinary excretion of neutrophil gelatinase-associated lipocalin (u-NGAL) in patients with normal renal function during hip arthroplasty. METHODS: In this randomized, double-blinded, placebo-controlled study, 40 patients referred for hip arthroplasty received either 6% HES 130/0.4 or isotonic saline 0.9%; 7.5 ml/kg during the first hour of surgery and 5 ml/kg during the following hours; 38 patients completed the study. U-NGAL, urine albumin, blood pressure, and plasma concentrations of creatinine, renin, NGAL, albumin, angiotensin-II, and aldosterone were measured before, during, and after surgery. U-NGAL was defined as primary outcome. RESULTS: There were no significant differences in U-NGAL (mean difference and 95% CI), plasma creatinine, and urine albumin during the study. U-NGAL and urine albumin increased significantly in both groups the morning after surgery but was normalized at follow-up after 10 to 12 days. Mean arterial pressure was significantly higher during the recovery period in the HES group compared with that in the control group (91 [13] and 83 [6] mmHg, mean [SD], P < 0.03). Plasma renin and angiotensin-II were nonsignificantly different in both groups, whereas plasma aldosterone was significantly lower in the HES group. Plasma albumin was reduced in both groups, but to a significantly lower level in the HES group. CONCLUSION: The study showed no evidence of a harmful effect of intraoperative infusion of 6% HES 130/0.4 on renal function in patients during hip arthroplasty. PMID- 25127212 TI - Repeated evolutionary changes of leaf morphology caused by mutations to a homeobox gene. AB - Elucidating the genetic basis of morphological changes in evolution remains a major challenge in biology. Repeated independent trait changes are of particular interest because they can indicate adaptation in different lineages or genetic and developmental constraints on generating morphological variation. In animals, changes to "hot spot" genes with minimal pleiotropy and large phenotypic effects underlie many cases of repeated morphological transitions. By contrast, only few such genes have been identified from plants, limiting cross-kingdom comparisons of the principles of morphological evolution. Here, we demonstrate that the REDUCED COMPLEXITY (RCO) locus underlies more than one naturally evolved change in leaf shape in the Brassicaceae. We show that the difference in leaf margin dissection between the sister species Capsella rubella and Capsella grandiflora is caused by cis-regulatory variation in the homeobox gene RCO-A, which alters its activity in the developing lobes of the leaf. Population genetic analyses in the ancestral C. grandiflora indicate that the more-active C. rubella haplotype is derived from a now rare or lost C. grandiflora haplotype via additional mutations. In Arabidopsis thaliana, the deletion of the RCO-A and RCO-B genes has contributed to its evolutionarily derived smooth leaf margin, suggesting the RCO locus as a candidate for an evolutionary hot spot. We also find that temperature responsive expression of RCO-A can explain the phenotypic plasticity of leaf shape to ambient temperature in Capsella, suggesting a molecular basis for the well-known negative correlation between temperature and leaf margin dissection. PMID- 25127211 TI - Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis. AB - BACKGROUND: Both air pollution and genetic variation have been shown to affect lung function. Their interaction has not been studied on a genome-wide scale to date. OBJECTIVES: We aimed to identify, in an agnostic fashion, genes that modify the association between long-term air pollution exposure and annual lung function decline in an adult population-based sample. METHODS: A two-stage genome-wide interaction study was performed. The discovery (n = 763) and replication (n = 3,896) samples were derived from the multi-center SAPALDIA cohort (Swiss Cohort Study on Air Pollution and Lung Disease in Adults). Annual rate of decline in the forced mid-expiratory flow (FEF25-75%) was the main end point. Multivariate linear regression analyses were used to identify potential multiplicative interactions between genotypes and 11-year cumulative PM10 exposure. RESULTS: We identified a cluster of variants intronic to the CDH13 gene as the only locus with genome-wide significant interactions. The strongest interaction was observed for rs2325934 (p = 8.8 * 10(-10)). Replication of the interaction between this CDH13 variant and cumulative PM10 exposure on annual decline in FEF25-75% was successful (p = 0.008). The interaction was not sensitive to adjustment for smoking or body weight. CONCLUSIONS: CDH13 is functionally linked to the adipokine adiponectin, an inflammatory regulator. Future studies need to confirm the interaction and assess how the result relates to previously observed interactions between air pollution and obesity on respiratory function. PMID- 25127214 TI - The receptor-like kinase FERONIA is required for mechanical signal transduction in Arabidopsis seedlings. AB - Among the myriad cues that constantly inform plant growth and development, mechanical forces are unique in that they are an intrinsic result of cellular turgor pressure and also imposed by the environment. Although the key role of mechanical forces in shaping plant architecture from the cellular level to the level of organ formation is well established, the components of the early mechanical signal transduction machinery remain to be defined at the molecular level. Here, we show that an Arabidopsis mutant lacking the receptor-like kinase FERONIA (FER) shows severely altered Ca(2+) signaling and growth responses to different forms of mechanical perturbation. Ca(2+) signals are either abolished or exhibit qualitatively different signatures in feronia (fer) mutants exposed to local touch or bending stimulation. Furthermore, mechanically induced upregulation of known touch-responsive genes is significantly decreased in fer mutants. In addition to these defects in mechanical signaling, fer mutants also exhibit growth phenotypes consistent with impaired mechanical development, including biased root skewing, an inability to penetrate hard agar layers, and abnormal growth responses to impenetrable obstacles. Finally, high-resolution kinematic analysis of root growth revealed that fer mutants show pronounced spatiotemporal fluctuations in root cell expansion profiles with a timescale of minutes. Based on these results, we propose that FER is a key regulator of mechanical Ca(2+) signaling and that FER-dependent mechanical signaling functions to regulate growth in response to external or intrinsic mechanical forces. PMID- 25127213 TI - Dynamic localization of the cyanobacterial circadian clock proteins. AB - BACKGROUND: The cyanobacterial circadian clock system has been extensively studied, and the structures, interactions, and biochemical activities of the central oscillator proteins (KaiA, KaiB, and KaiC) have been well elucidated. Despite this rich repository of information, little is known about the distribution of these proteins within the cell. RESULTS: Here we report that KaiA and KaiC localize as discrete foci near a single pole of cells in a clock dependent fashion, with enhanced polar localization observed at night. KaiA localization is dependent on KaiC; consistent with this notion, KaiA and KaiC colocalize with each other, as well as with CikA, a key input and output factor previously reported to display unipolar localization. The molecular mechanism that localizes KaiC to the poles is conserved in Escherichia coli, another Gram negative rod-shaped bacterium, suggesting that KaiC localization is not dependent on other clock- or cyanobacterial-specific factors. Moreover, expression of CikA mutant variants that distribute diffusely results in the striking delocalization of KaiC. CONCLUSIONS: This work shows that the cyanobacterial circadian system undergoes a circadian orchestration of subcellular organization. We propose that the observed spatiotemporal localization pattern represents a novel layer of regulation that contributes to the robustness of the clock by facilitating protein complex formation and synchronizing the clock with environmental stimuli. PMID- 25127215 TI - Class I TCP-DELLA interactions in inflorescence shoot apex determine plant height. AB - Regulation of plant height, one of the most important agronomic traits, is the focus of intensive research for improving crop performance. Stem elongation takes place as a result of repeated cell divisions and subsequent elongation of cells produced by apical and intercalary meristems. The gibberellin (GA) phytohormones have long been known to control stem and internodal elongation by stimulating the degradation of nuclear growth-repressing DELLA proteins; however, the mechanism allowing GA-responsive growth is only slowly emerging. Here, we show that DELLAs directly regulate the activity of the plant-specific class I TCP transcription factor family, key regulators of cell proliferation. Our results demonstrate that class I TCP factors directly bind the promoters of core cell-cycle genes in Arabidopsis inflorescence shoot apices while DELLAs block TCP function by binding to their DNA-recognition domain. GAs antagonize such repression by promoting DELLA destruction and therefore cause a concomitant accumulation of TCP factors on promoters of cell-cycle genes. Consistent with this model, the quadruple mutant tcp8 tcp14 tcp15 tcp22 exhibits severe dwarfism and reduced responsiveness to GA action. Altogether, we conclude that GA-regulated DELLA-TCP interactions in inflorescence shoot apex provide a novel mechanism to control plant height. PMID- 25127216 TI - Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin. AB - Tissue microenvironments are characterized not only in terms of chemical composition but also by collective properties such as stiffness, which influences the contractility of a cell, its adherent morphology, and even differentiation. The nucleoskeletal protein lamin-A,C increases with matrix stiffness, confers nuclear mechanical properties, and influences differentiation of mesenchymal stem cells (MSCs), whereas B-type lamins remain relatively constant. Here we show in single-cell analyses that matrix stiffness couples to myosin-II activity to promote lamin-A,C dephosphorylation at Ser22, which regulates turnover, lamina physical properties, and actomyosin expression. Lamin-A,C phosphorylation is low in interphase versus dividing cells, and its levels rise with states of nuclear rounding in which myosin-II generates little to no tension. Phosphorylated lamin A,C localizes to nucleoplasm, and phosphorylation is enriched on lamin-A,C fragments and is suppressed by a cyclin-dependent kinase (CDK) inhibitor. Lamin A,C knockdown in primary MSCs suppresses transcripts predominantly among actomyosin genes, especially in the serum response factor (SRF) pathway. Levels of myosin-IIA thus parallel levels of lamin-A,C, with phosphosite mutants revealing a key role for phosphoregulation. In modeling the system as a parsimonious gene circuit, we show that tension-dependent stabilization of lamin A,C and myosin-IIA can suitably couple nuclear and cell morphology downstream of matrix mechanics. PMID- 25127218 TI - Anisotropic diffusion of macromolecules in the contiguous nucleocytoplasmic fluid during eukaryotic cell division. AB - Character and rapidity of protein diffusion in intracellular fluids are key determinants of the dynamics and steady state of a plethora of biochemical reactions. So far, an anomalous diffusion in cytoplasmic fluids with viscoelastic and even glassy characteristics has been reported in a variety of organisms on several length scales and timescales. Here, we show that the contiguous fluid of former cytoplasm and nucleoplasm features an anisotropically varying diffusion of macromolecules during eukaryotic cell division. In metaphase, diffusion in the contiguous nucleocytoplasmic fluid appears less anomalous along the spindle axis as compared to perpendicular directions. As a consequence, the long-time diffusion of macromolecules preferentially points along the spindle axis, leading to prolonged residence of macromolecules in the spindle region. Based on our experimental data, we suggest that anisotropic diffusion facilitates the encounter and interaction of spindle-associated proteins, e.g., during the formation of a dynamic spindle matrix. PMID- 25127217 TI - Regulation of YAP by mechanical strain through Jnk and Hippo signaling. AB - Mechanical forces affect all the tissues of our bodies. Experiments conducted mainly on cultured cells have established that altering these forces influences cell behaviors, including migration, differentiation, apoptosis, and proliferation [1, 2]. The transcriptional coactivator YAP has been identified as a nuclear relay of mechanical signals, but the molecular mechanisms that lead to YAP activation were not identified [3]. YAP is the main transcriptional effector of the Hippo signaling pathway, a major growth regulatory pathway within metazoa [4], but at least in some instances, the influence of mechanical strain on YAP was reported to be independent of Hippo signaling [5, 6]. Here, we identify a molecular pathway that can promote the proliferation of cultured mammary epithelial cells in response to cyclic or static stretch. These mechanical stimuli are associated with increased activity of the transcriptional coactivator YAP, which is due at least in part to inhibition of Hippo pathway activity. Much of this influence on Hippo signaling can be accounted for by the activation of c Jun N-terminal kinase (JNK) activity by mechanical strain and subsequent inhibition of Hippo signaling by JNK. LATS1 is a key negative regulator of YAP within the Hippo pathway, and we further show that cyclic stretch is associated with a JNK-dependent increase in binding of a LATS inhibitor, LIMD1, to the LATS1 kinase and that reduction of LIMD1 expression suppresses the activation of YAP by cyclic stretch. Together, these observations establish a pathway for mechanical regulation of cell proliferation via JNK-mediated inhibition of Hippo signaling. PMID- 25127219 TI - Clonal relationships impact neuronal tuning within a phylogenetically ancient vertebrate brain structure. AB - Understanding how neurons acquire specific response properties is a major goal in neuroscience. Recent studies in mouse neocortex have shown that "sister neurons" derived from the same cortical progenitor cell have a greater probability of forming synaptic connections with one another and are biased to respond to similar sensory stimuli. However, it is unknown whether such lineage-based rules contribute to functional circuit organization across different species and brain regions. To address this question, we examined the influence of lineage on the response properties of neurons within the optic tectum, a visual brain area found in all vertebrates. Tectal neurons possess well-defined spatial receptive fields (RFs) whose center positions are retinotopically organized. If lineage relationships do not influence the functional properties of tectal neurons, one prediction is that the RF positions of sister neurons should be no more (or less) similar to one another than those of neighboring control neurons. To test this prediction, we developed a protocol to unambiguously identify the daughter neurons derived from single tectal progenitor cells in Xenopus laevis tadpoles. We combined this approach with in vivo two-photon calcium imaging in order to characterize the RF properties of tectal neurons. Our data reveal that the RF centers of sister neurons are significantly more similar than would be expected by chance. Ontogenetic relationships therefore influence the fine-scale topography of the retinotectal map, indicating that lineage relationships may represent a general and evolutionarily conserved principle that contributes to the organization of neural circuits. PMID- 25127222 TI - Proposed US Food and Drug Administration guidance for industry on distributing medical publications about the risks of prescription drugs and biological products: a misguided approach. PMID- 25127220 TI - WOX5 suppresses CYCLIN D activity to establish quiescence at the center of the root stem cell niche. AB - In Arabidopsis, stem cells maintain the provision of new cells for root growth. They surround a group of slowly dividing cells named the quiescent center (QC), and, together, they form the stem cell niche (SCN). The QC acts as the signaling center of the SCN, repressing differentiation of the surrounding stem cells and providing a pool of cells able to replace damaged stem cells. Maintenance of the stem cells depends on the transcription factor WUSCHEL-RELATED HOMEOBOX 5 (WOX5), which is specifically expressed in the QC. However, the molecular mechanisms by which WOX5 promotes stem cell fate and whether WOX5 regulates proliferation of the QC are unknown. Here, we reveal a new role for WOX5 in restraining cell division in the cells of the QC, thereby establishing quiescence. In contrast, WOX5 and CYCD3;3/CYCD1;1 both promote cell proliferation in the nascent columella. The additional QC divisions occurring in wox5 mutants are suppressed in mutant combinations with the D type cyclins CYCD3;3 and CYCD1;1. Moreover, ectopic expression of CYCD3;3 in the QC is sufficient to induce cell division in the QC. WOX5 thus suppresses QC divisions that are otherwise promoted by CYCD3;3 and CYCD1;1, in part by interacting with the CYCD3;3 promoter to repress CYCD3;3 expression in the QC. Therefore, we propose a specific role for WOX5 in initiating and maintaining quiescence of the QC by excluding CYCD activity from the QC. PMID- 25127223 TI - Potential torsades de pointes triggered by hypokalemia related to olanzapine in a patient with implantable cardioverter-defibrillator. PMID- 25127224 TI - Continuing quality enhancement. PMID- 25127221 TI - Rhythms in energy storage control the ability of the cyanobacterial circadian clock to reset. AB - Circadian clocks are oscillatory systems that schedule daily rhythms of organismal behavior. The ability of the clock to reset its phase in response to external signals is critical for proper synchronization with the environment. In the model clock from cyanobacteria, the KaiABC proteins that comprise the core oscillator are directly sensitive to metabolites. Reduced ATP/ADP ratio and oxidized quinones cause clock phase shifts in vitro. However, it is unclear what determines the metabolic response of the cell to darkness and thus the magnitude of clock resetting. We show that the cyanobacterial circadian clock generates a rhythm in metabolism that causes cells to accumulate glycogen in anticipation of nightfall. Mutation of the histidine kinase CikA creates an insensitive clock input phenotype by misregulating clock output genome wide, leading to overaccumulation of glycogen and subsequently high ATP in the dark. Conversely, we show that disruption of glycogen metabolism results in low ATP in the dark and makes the clock hypersensitive to dark pulses. The observed changes in cellular energy are sufficient to recapitulate phase-shifting phenotypes in an in vitro model of the clock. Our results show that clock-input phenotypes can arise from metabolic dysregulation and illustrate a framework for circadian biology where clock outputs feed back through metabolism to control input mechanisms. PMID- 25127225 TI - Ultrasound of the fetal veins part 2: Veins at the cardiac level. AB - In recent years the advent of high-resolution and color Doppler ultrasound has enabled a more comprehensive examination of the veins at the cardiac level. These veins include both the superior and inferior vena cava, the pulmonary veins, the azygos vein, the coronary sinus, and the brachiocephalic (or innominate) vein. This article gives a review of the normal and abnormal conditions of the cardiac venous system. Normal anatomy and abnormal findings of these veins are demonstrated by grayscale and color Doppler. Three groups of anomalies are presented: 1) the interrupted inferior vena cava with azygos continuity, 2) the left persisting superior vena cava and 3) the total and partial anomalous pulmonary venous connections. Many of these abnormal findings can be detected by a dedicated examination of the veins during fetal echocardiography, but some anomalies are detectable by focusing on indirect signs such as the compensatory dilation of other veins. PMID- 25127226 TI - Letter to the editor: Mostbeck G. Elastography everywhere--now even the lungs! Ultraschall in Med. 2014; 35: 5 - 8. PMID- 25127227 TI - Associations between depression and diabetes in the community: do symptom dimensions matter? Results from the Gutenberg Health Study. AB - OBJECTIVES: While a bidirectional relationship between diabetes and depression has been established, there is little knowledge if the associations are due to somatic-affective or cognitive-affective dimensions of depression. RESEARCH DESIGN AND METHODS: In a population-based, representative survey of 15.010 participants we therefore studied the associations of the two dimensions of depression with diabetes and health care utilization among depressed and diabetic participants. Depression was assessed by the Patient Health Questionnaire PHQ-9. RESULTS: We found a linear and consistent association between the intensity of depression and the presence of diabetes increasing from 6.9% in no or minimal depression to 7.6% in mild, 9% in moderate and 10.5% in severe depression. There was a strong positive association between somatic-affective symptoms but not with cognitive-affective symptoms and diabetes. Depression and diabetes were both independently related to somatic health care utilisation. CONCLUSIONS: Diabetes and depression are associated, and the association is primarily driven by the somatic-affective component of depression. The main limitation of our study pertains to the cross-sectional data acquisition. Further longitudinal work on the relationship of obesity and diabetes should differentiate the somatic and the cognitive symptoms of depression. PMID- 25127228 TI - Influence of tetracycline on the microbial community composition and activity of nitrifying biofilms. AB - The present work aims to evaluate the bacterial composition and activity (carbon and nitrogen removal) of nitrifying biofilms exposed to 50 MUg L(-1) of tetracycline. The tetracycline removal efficiency and the occurrence of tetracycline resistance (tet) genes were also studied. Two sequencing batch biofilm reactors (SBBRs) fed with synthetic wastewater were operated without (SBBR1) and with (SBBR2) the antibiotic. Both SBBRs showed similar organic matter biodegradation and nitrification activity. Tetracycline removal was about 28% and biodegradation was probably the principal removal mechanism of the antibiotic. Polymerase chain reaction-denaturing gradient gel electrophoresis analysis of the bacterial community showed shifts leading to not only the fading of some ribotypes, but also the emergence of new ones in the biofilm with tetracycline. The study of the tet genes showed that tet(S) was only detected in the biofilm with tetracycline, suggesting a relationship between its occurrence and the presence of the antibiotic. PMID- 25127229 TI - Chemical and mechanical defenses vary among maternal lines and leaf ages in Verbascum thapsus L. (Scrophulariaceae) and reduce palatability to a generalist insect. AB - Intra-specific variation in host-plant quality affects herbivore foraging decisions and, in turn, herbivore foraging decisions mediate plant fitness. In particular, variation in defenses against herbivores, both among and within plants, shapes herbivore behavior. If variation in defenses is genetically based, it can respond to natural selection by herbivores. We quantified intra-specific variation in iridoid glycosides, trichome length, and leaf strength in common mullein (Verbascum thapsus L, Scrophulariaceae) among maternal lines within a population and among leaves within plants, and related this variation to feeding preferences of a generalist herbivore, Trichopulsia ni Hubner. We found significant variation in all three defenses among maternal lines, with T. ni preferring plants with lower investment in chemical, but not mechanical, defense. Within plants, old leaves had lower levels of all defenses than young leaves, and were strongly preferred by T. ni. Caterpillars also preferred leaves with trichomes removed to leaves with trichomes intact. Differences among maternal lines indicate that phenotypic variation in defenses likely has a genetic basis. Furthermore, these results reveal that the feeding behaviors of T. ni map onto variation in plant defense in a predictable way. This work highlights the importance of variation in host-plant quality in driving interactions between plants and their herbivores. PMID- 25127230 TI - Behavior of the potential antitumor V(IV)O complexes formed by flavonoid ligands. 1. Coordination modes and geometry in solution and at the physiological pH. AB - The coordination modes and geometry assumed in solution by the potent antitumor oxidovanadium(IV) complexes formed by different flavonoids were studied by spectroscopic (Electron Paramagnetic Resonance, EPR) and computational (Density Functional Theory, DFT) methods. A series of bidentate flavonoid ligands (L) with increasing structural complexity was examined, which can involve (CO, O(-)) donors and formation of five- and six-membered chelate rings, or (O(-), O(-)) donors and five-membered chelate rings. The geometry corresponding to these coordination modes can be penta-coordinated, [VOL2], or cis-octahedral, cis [VOL2(H2O)]. The results show that, at physiological pH, ligands provided with (CO, O(-)) donor set yield cis-octahedral species with "maltol-like" coordination when five-membered chelate rings are formed (as with 3-hydroxyflavone), while penta-coordinated structures with "acetylacetone-like" coordination are preferred when the chelate rings are six-membered (as with chrysin). When both the binding modes are possible, as with morin, the "acetylacetone-like" coordination is observed. For the ligands containing a catecholic donor set, such as 7,8 dihydroxyflavone, baicalein, fisetin, quercetin and rutin, the formation of square pyramidal complexes with (O(-), O(-)) "catechol-like" coordination and five-membered chelate rings is preferred at physiological pH. The determination of the different coordination modes and geometry is important to define the biotransformation in the blood and the interaction of these complexes with the biological membranes. PMID- 25127231 TI - Pallidal neurostimulation in patients with medication-refractory cervical dystonia: a randomised, sham-controlled trial. AB - BACKGROUND: Cervical dystonia is managed mainly by repeated botulinum toxin injections. We aimed to establish whether pallidal neurostimulation could improve symptoms in patients not adequately responding to chemodenervation or oral drug treatment. METHODS: In this randomised, sham-controlled trial, we recruited patients with cervical dystonia from centres in Germany, Norway, and Austria. Eligible patients (ie, those aged 18-75 years, disease duration >=3 years, Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] severity score >=15 points) were randomly assigned (1:1) to receive active neurostimulation (frequency 180 Hz; pulse width 120 MUs; amplitude 0.5 V below adverse event threshold) or sham stimulation (amplitude 0 V) by computer-generated randomisation lists with randomly permuted block lengths stratified by centre. All patients, masked to treatment assignment, were implanted with a deep brain stimulation device and received their assigned treatment for 3 months. Neurostimulation was activated in the sham group at 3 months and outcomes were reassessed in all patients after 6 months of active treatment. Treating physicians were not masked. The primary endpoint was the change in the TWSTRS severity score from baseline to 3 months, assessed by two masked dystonia experts using standardised videos, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148889. FINDINGS: Between Jan 19, 2006, and May 29, 2008, we recruited 62 patients, of whom 32 were randomly assigned to neurostimulation and 30 to sham stimulation. Outcome data were recorded in 60 (97%) patients at 3 months and 56 (90%) patients at 6 months. At 3 months, the reduction in dystonia severity was significantly greater with neurostimulation (-5.1 points [SD 5.1], 95% CI -7.0 to -3.5) than with sham stimulation (-1.3 [2.4], -2.2 to -0.4, p=0.0024; mean between-group difference 3.8 points, 1.8 to 5.8) in the intention-to-treat population. Over the course of the study, 21 adverse events (five serious) were reported in 11 (34%) of 32 patients in the neurostimulation group compared with 20 (11 serious) in nine (30%) of 30 patients in the sham-stimulation group. Serious adverse events were typically related to the implant procedure or the implanted device, and 11 of 16 resolved without sequelae. Dysarthria (in four patients assigned to neurostimulation vs three patients assigned to sham stimulation), involuntary movements (ie, dyskinesia or worsening of dystonia; five vs one), and depression (one vs two) were the most common non-serious adverse events reported during the course of the study. INTERPRETATION: Pallidal neurostimulation for 3 months is more effective than sham stimulation at reducing symptoms of cervical dystonia. Extended follow-up is needed to ascertain the magnitude and stability of chronic neurostimulation effects before this treatment can be recommended as routine for patients who are not responding to conventional medical therapy. FUNDING: Medtronic. PMID- 25127233 TI - Lost in space: sleep. PMID- 25127232 TI - Prevalence of sleep deficiency and use of hypnotic drugs in astronauts before, during, and after spaceflight: an observational study. AB - BACKGROUND: Sleep deprivation and fatigue are common subjective complaints among astronauts. Previous studies of sleep and hypnotic drug use in space have been limited to post-flight subjective survey data or in-flight objective data collection from a small number of crew members. We aimed to characterise representative sleep patterns of astronauts on both short-duration and long duration spaceflight missions. METHODS: For this observational study, we recruited crew members assigned to Space Transportation System shuttle flights with in-flight experiments between July 12, 2001, and July 21, 2011, or assigned to International Space Station (ISS) expeditions between Sept 18, 2006, and March 16, 2011. We assessed sleep-wake timing objectively via wrist actigraphy, and subjective sleep characteristics and hypnotic drug use via daily logs, in-flight and during Earth-based data-collection intervals: for 2 weeks scheduled about 3 months before launch, 11 days before launch until launch day, and for 7 days upon return to Earth. FINDINGS: We collected data from 64 astronauts on 80 space shuttle missions (26 flights, 1063 in-flight days) and 21 astronauts on 13 ISS missions (3248 in-flight days), with ground-based data from all astronauts (4014 days). Crew members attempted and obtained significantly less sleep per night as estimated by actigraphy during space shuttle missions (7.35 h [SD 0.47] attempted, 5.96 h [0.56] obtained), in the 11 days before spaceflight (7.35 h [0.51], 6.04 h [0.72]), and about 3 months before spaceflight (7.40 h [0.59], 6.29 h [0.67]) compared with the first week post-mission (8.01 h [0.78], 6.74 h [0.91]; p<0.0001 for both measures). Crew members on ISS missions obtained significantly less sleep during spaceflight (6.09 h [0.67]), in the 11 days before spaceflight (5.86 h [0.94]), and during the 2-week interval scheduled about 3 months before spaceflight (6.41 h [SD 0.65]) compared with in the first week post-mission (6.95 h [1.04]; p<0.0001). 61 (78%) of 78 shuttle-mission crew members reported taking a dose of sleep-promoting drug on 500 (52%) of 963 nights; 12 (75%) of 16 ISS crew members reported using sleep-promoting drugs. INTERPRETATION: Sleep deficiency in astronauts was prevalent not only during space shuttle and ISS missions, but also throughout a 3 month preflight training interval. Despite chronic sleep curtailment, use of sleep-promoting drugs was pervasive during spaceflight. Because chronic sleep loss leads to performance decrements, our findings emphasise the need for development of effective countermeasures to promote sleep. FUNDING: The National Aeronautics and Space Administration. PMID- 25127234 TI - Deep brain stimulation for cervical dystonia. PMID- 25127237 TI - Reporting tumor molecular heterogeneity in histopathological diagnosis. AB - BACKGROUND: Detection of molecular tumor heterogeneity has become of paramount importance with the advent of targeted therapies. Analysis for detection should be comprehensive, timely and based on routinely available tumor samples. AIM: To evaluate the diagnostic potential of targeted multigene next-generation sequencing (TM-NGS) in characterizing gastrointestinal cancer molecular heterogeneity. METHODS: 35 gastrointestinal tract tumors, five of each intestinal type gastric carcinomas, pancreatic ductal adenocarcinomas, pancreatic intraductal papillary mucinous neoplasms, ampulla of Vater carcinomas, hepatocellular carcinomas, cholangiocarcinomas, pancreatic solid pseudopapillary tumors were assessed for mutations in 46 cancer-associated genes, using Ion Torrent semiconductor-based TM-NGS. One ampulla of Vater carcinoma cell line and one hepatic carcinosarcoma served to assess assay sensitivity. TP53, PIK3CA, KRAS, and BRAF mutations were validated by conventional Sanger sequencing. RESULTS: TM-NGS yielded overlapping results on matched fresh-frozen and formalin fixed paraffin-embedded (FFPE) tissues, with a mutation detection limit of 1% for fresh-frozen high molecular weight DNA and 2% for FFPE partially degraded DNA. At least one somatic mutation was observed in all tumors tested; multiple alterations were detected in 20/35 (57%) tumors. Seven cancers displayed significant differences in allelic frequencies for distinct mutations, indicating the presence of intratumor molecular heterogeneity; this was confirmed on selected samples by immunohistochemistry of p53 and Smad4, showing concordance with mutational analysis. CONCLUSIONS: TM-NGS is able to detect and quantitate multiple gene alterations from limited amounts of DNA, moving one step closer to a next-generation histopathologic diagnosis that integrates morphologic, immunophenotypic, and multigene mutational analysis on routinely processed tissues, essential for personalized cancer therapy. PMID- 25127238 TI - Interplay between parasitism and host ontogenic resistance in the epidemiology of the soil-borne plant pathogen Rhizoctonia solani. AB - Spread of soil-borne fungal plant pathogens is mainly driven by the amount of resources the pathogen is able to capture and exploit should it behave either as a saprotroph or a parasite. Despite their importance in understanding the fungal spread in agricultural ecosystems, experimental data related to exploitation of infected host plants by the pathogen remain scarce. Using Rhizoctonia solani / Raphanus sativus as a model pathosystem, we have obtained evidence on the link between ontogenic resistance of a tuberizing host and (i) its susceptibility to the pathogen and (ii) after infection, the ability of the fungus to spread in soil. Based on a highly replicable experimental system, we first show that infection success strongly depends on the host phenological stage. The nature of the disease symptoms abruptly changes depending on whether infection occurred before or after host tuberization, switching from damping-off to necrosis respectively. Our investigations also demonstrate that fungal spread in soil still depends on the host phenological stage at the moment of infection. High, medium, or low spread occurred when infection was respectively before, during, or after the tuberization process. Implications for crop protection are discussed. PMID- 25127239 TI - Crystal structure of a complex of NOD1 CARD and ubiquitin. AB - The Caspase Recruitment Domain (CARD) from the innate immune receptor NOD1 was crystallized with Ubiquitin (Ub). NOD1 CARD was present as a helix-swapped homodimer similar to other structures of NOD1 CARD, and Ub monomers formed a homodimer similar in conformation to Lys48-linked di-Ub. The interaction between NOD1 CARD and Ub in the crystal was mediated by novel binding sites on each molecule. Comparisons of these sites to previously identified interaction surfaces on both molecules were made along with discussion of their potential functional significance. PMID- 25127240 TI - A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women. AB - A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. The objective of this double blinded, placebo controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate Nugent score, the effect of 3 days of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5*109 CFU each) on the microbiota and host response. The probiotic treatment did not result in an improved Nugent score when compared to when placebo. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the relative abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. A decrease in Atopobium was also observed. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response including effects on pattern recognition receptors such as TLR2 while also affecting epithelial barrier function. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle molecular changes induced by the host to instillation of probiotic strains. TRIAL REGISTRATION: ClinicalTrials.gov NCT02139839. PMID- 25127243 TI - Prevention of invasive pneumococcal diseases: beyond cultures. PMID- 25127241 TI - Integrating transcriptomics with metabolic modeling predicts biomarkers and drug targets for Alzheimer's disease. AB - Accumulating evidence links numerous abnormalities in cerebral metabolism with the progression of Alzheimer's disease (AD), beginning in its early stages. Here, we integrate transcriptomic data from AD patients with a genome-scale computational human metabolic model to characterize the altered metabolism in AD, and employ state-of-the-art metabolic modelling methods to predict metabolic biomarkers and drug targets in AD. The metabolic descriptions derived are first tested and validated on a large scale versus existing AD proteomics and metabolomics data. Our analysis shows a significant decrease in the activity of several key metabolic pathways, including the carnitine shuttle, folate metabolism and mitochondrial transport. We predict several metabolic biomarkers of AD progression in the blood and the CSF, including succinate and prostaglandin D2. Vitamin D and steroid metabolism pathways are enriched with predicted drug targets that could mitigate the metabolic alterations observed. Taken together, this study provides the first network wide view of the metabolic alterations associated with AD progression. Most importantly, it offers a cohort of new metabolic leads for the diagnosis of AD and its treatment. PMID- 25127245 TI - A lightweight distributed framework for computational offloading in mobile cloud computing. AB - The latest developments in mobile computing technology have enabled intensive applications on the modern Smartphones. However, such applications are still constrained by limitations in processing potentials, storage capacity and battery lifetime of the Smart Mobile Devices (SMDs). Therefore, Mobile Cloud Computing (MCC) leverages the application processing services of computational clouds for mitigating resources limitations in SMDs. Currently, a number of computational offloading frameworks are proposed for MCC wherein the intensive components of the application are outsourced to computational clouds. Nevertheless, such frameworks focus on runtime partitioning of the application for computational offloading, which is time consuming and resources intensive. The resource constraint nature of SMDs require lightweight procedures for leveraging computational clouds. Therefore, this paper presents a lightweight framework which focuses on minimizing additional resources utilization in computational offloading for MCC. The framework employs features of centralized monitoring, high availability and on demand access services of computational clouds for computational offloading. As a result, the turnaround time and execution cost of the application are reduced. The framework is evaluated by testing prototype application in the real MCC environment. The lightweight nature of the proposed framework is validated by employing computational offloading for the proposed framework and the latest existing frameworks. Analysis shows that by employing the proposed framework for computational offloading, the size of data transmission is reduced by 91%, energy consumption cost is minimized by 81% and turnaround time of the application is decreased by 83.5% as compared to the existing offloading frameworks. Hence, the proposed framework minimizes additional resources utilization and therefore offers lightweight solution for computational offloading in MCC. PMID- 25127244 TI - Vaccine effectiveness of the pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against clinically suspected invasive pneumococcal disease: a cluster-randomised trial. AB - BACKGROUND: Vaccine effectiveness of pneumococcal conjugate vaccines against culture-confirmed invasive pneumococcal disease has been well documented. In the Finnish Invasive Pneumococcal disease (FinIP) trial, we reported vaccine effectiveness and absolute rate reduction against laboratory-confirmed invasive pneumococcal disease (confirmation by culture or antigen or DNA detection irrespective of serotype). Here, we assessed vaccine effectiveness of PHiD-CV10 against clinically suspected invasive pneumococcal disease in children by use of diagnoses coded in hospital discharge registers. METHODS: For this phase 3/4 cluster-randomised, double-blind trial, undertaken between Feb 18, 2009, and Dec 31, 2011, in municipal health-care centres and the Tampere University Vaccine Research Centre (Finland), we randomly assigned (2:2:1:1) 78 clusters into PHiD CV10 three plus one, PHiD-CV10 two plus one, control three plus one, control two plus one groups (26:26:13:13 clusters) to give PHiD-CV10 in either three plus one or two plus one schedule (if enrolled before 7 months of age; infant schedules), two plus one (if enrolled between 7 and 11 months; catch-up schedules), and two doses at least 6 months apart (if enrolled between 12 and 18 months; catch-up schedules). Children were eligible if they had not received and were not anticipated to receive any of the study vaccines and had no general contraindications to vaccinations. We collected all inpatient and outpatient discharge notifications from the national hospital discharge register with International Classification of Diseases (ICD) 10 diagnoses compatible with invasive pneumococcal disease or unspecified sepsis, and verified data with patient files. We excluded invasive pneumococcal disease cases confirmed by positive culture or DNA/RNA detection from normally sterile body fluid. The primary objective was to estimate vaccine effectiveness against all register based non-laboratory-confirmed invasive pneumococcal disease or unspecified sepsis and patient-file verified non-laboratory-confirmed invasive pneumococcal disease in infants younger than 7 months at enrolment. Masked follow-up lasted from the date of the first vaccination to Dec 31, 2011. Vaccine effectiveness was calculated against all episodes. This trial is registered with ClinicalTrials.gov, numbers NCT00861380 and NCT00839254. FINDINGS: We enrolled 47,366 children. On the basis of ICD-10 diagnoses, we recorded 264 episodes of register-based non-laboratory-confirmed invasive pneumococcal disease or unspecified sepsis, of which 102 were patient-file verified non-laboratory confirmed invasive pneumococcal disease. The vaccine effectiveness was 50% (95% CI 32-63) in the 30,527 infants with three plus one and two plus one schedules combined and the absolute incidence rate reduction was 207 episodes per 100,000 person-years (95% CI 127-286). The vaccine effectiveness against the patient-file verified non-laboratory-confirmed invasive pneumococcal disease was 71% (95% CI 52-83) in infant three plus one and two plus one schedules combined. The absolute rate reduction was 142 episodes per 100,000 person-years (95% CI 91-191) in infant cohorts. INTERPRETATION: This vaccine-probe analysis is the first report showing the effect of pneumococcal conjugate vaccines on clinically suspected invasive pneumococcal disease. The absolute rate reduction was markedly higher compared with laboratory-confirmed invasive pneumococcal disease, which implies low sensitivity of the laboratory-based case definitions and subsequently higher public health effect of pneumococcal conjugate vaccines against invasive pneumococcal disease than previously estimated. FUNDING: GlaxoSmithKline Biologicals SA and National Institute for Health and Welfare (THL), Finland. PMID- 25127246 TI - The use of social networking services and their relationship with the big five personality model and job satisfaction in Korea. AB - Social networking services (SNSs) have been garnering attention from society due to their recent rapid growth. This study examines whether SNS use can affect the relationship between the Big Five personality model and individual job satisfaction. Based on a sample of 1,452 workers in Korea, the results of this study indicate that the Big Five personality model (extroversion, agreeableness, and neuroticism) was significantly related to individual job satisfaction. Further, SNS use moderated the relationship between extroversion and neuroticism with individual job satisfaction. Also, SNS use was found to increase job satisfaction of Korean workers who are more extroverted, while it also affected job satisfaction of Korean workers with low agreeableness. As SNS use plays an important role in the workplace, it is necessary to realize and appreciate the importance of SNSs in shaping and promoting job satisfaction of working individuals. PMID- 25127247 TI - A method for predicting the number of active bubbles in sonochemical reactors. AB - Knowledge of the number of active bubbles in acoustic cavitation field is very important for the prediction of the performance of ultrasonic reactors toward most chemical processes induced by ultrasound. The literature in this field is scarce, probably due to the complicated nature of the phenomena. We introduce here a relatively simple semi-empirical method for predicting the number of active bubbles in an acoustic cavitation field. By coupling the bubble dynamics in an acoustical field with chemical kinetics occurring in the bubble during oscillation, the amount of the radical species OH and HO2 and molecular H2O2 released by a single bubble was estimated. Knowing that the H2O2 measured experimentally during sonication of water comes from the recombination of hydroxyl (OH) and perhydroxyl (HO2) radicals in the liquid phase and assuming that in sonochemistry applications, the cavitation is transient and the bubble fragments at the first collapse, the number of bubbles formed per unit time per unit volume is then easily determined using material balances for H2O2, OH and HO2 in the liquid phase. The effect of ultrasonic frequency on the number of active bubbles was examined. It was shown that increasing ultrasonic frequency leads to a substantial increase in the number of bubbles formed in the reactor. PMID- 25127248 TI - Effect of citric acid induced deflocculation on the ultrasonic pretreatment efficiency of dairy waste activated sludge. AB - In this investigation, the application of citric acid was explored for the removal of extracellular polymeric substance (EPS) from waste activated sludge (WAS), followed by ultrasonic pretreatment, which enhanced the subsequent anaerobic biodegradability. EPS was removed with 0.05g/g SS of citric acid. The chemical oxygen demand (COD) solubilization and suspended solids (SS) reduction that occurred for specific energy input of 171.9kJ/kg TS, in deflocculated (EPS removed and ultrasonically pretreated) sludges were found to be 22.70% and 20.28% and was comparatively higher, than the flocculated (with EPS and ultrasonically pretreated). The biogas yield potential of flocculated and deflocculated sludges (specific energy input - 171.9kJ/kgTS) was found to be 0.212L/(gVS) and 0.435L/(gVS), respectively. Accordingly, the deflocculation and ultrasonic pretreatment improved the anaerobic biodegradability efficiently. Thus, this chemo mediated sonic pretreatment is an effective method for enhancing biodegradability and improving clean energy generation from WAS. PMID- 25127249 TI - Colonization of later life? Laypersons' and users' agency regarding anti-aging medicine in Germany. AB - Anti-aging medicine is regarded as a significant trend in contemporary Western societies. Foucauldian gerontology provides some of the dominant theoretical perspectives on this trend in social and cultural theory. Proceeding from its interpretation and critique of anti-aging in terms of medicalization and responsibilization of aging, we explore by means of qualitative socio-empirical research how interested laypersons as well as non-professional users in the German context actually perceive of and deal with the medical claims and moral imperatives surrounding anti-aging medicine. The study is based on 12 focus groups and 20 narrative interviews (96 participants all included). They were conducted in Germany between 2011 and 2012, and analyzed by qualitative content analysis as well as comparative sequence analysis. The empirical findings indicate that in everyday life, interested laypersons and non-professional users employ different strategies for dealing with anti-aging products and services, corresponding to different degrees of affirmation and rejection. Four strategies could be identified: (a) medical optimism, (b) preventive maximalism, (c) ritualized well-being, and (d) considerate rejection. Also, each type was problematized and arguments against it were expressed. Overall, these findings show how our participants develop viable strategies to put the relevance of medical knowledge and moral imperatives for their own lives into perspective. This sheds light on laypersons' and users' agency-that is, their active role and deliberative space in the uptake, adaptation, and integration of anti-aging into their personal life. These empirical findings contribute to an enriched picture of the actual practice of anti-aging in concrete national and socio-cultural settings. This can help to differentiate the evaluation and thus make its critique more context sensitive, adequate, and targeted. PMID- 25127250 TI - Cognitive functioning among patients with diabetic foot. AB - AIMS: Using diabetic foot (DF) as an indicator of severe diabetes, we aimed to investigate the cognitive profile of DF patients and the relations between cognitive functioning and both diabetes complications and comorbidities. METHODS: Dementia-free patients with DF aged 30-90 (n=153) were assessed through medical records and a cognitive battery. Information on diabetes complications and comorbidities was collected via interview; glycated hemoglobin (HbA1c) was tested. Data were analyzed using robust logistic or quantile regression adjusted for potential confounders. RESULTS: The mean Mini-Mental Examination (MMSE) score of patients was 24.6 (SD=3.6), and 40% had global cognitive dysfunction (MMSE <=24). Among elderly patients (aged >=65), MMSE impairment was related to amputation (OR 3.59, 95% CI 1.07-12.11). Episodic memory impairment was associated with foot amputation (OR 4.13, 95% CI 1.11-15.28) and microvascular complications (OR 9.68, 95% CI 1.67-56.06). Further, elderly patients with HbA1c <7% had increased odds of psychomotor slowness (OR 7.75, 95% CI 1.55-38.73) and abstract reasoning impairment (OR 4.49, 95% CI: 1.15-17.46). However, such significant associations were not shown in adult patients aged <65. CONCLUSION: Amputation, microvascular diseases and glycemic control were associated with impaired global cognitive function and its domains among patients aged >=65. PMID- 25127251 TI - A cluster randomized-controlled trial of a classroom-based drama workshop program to improve mental health outcomes among immigrant and refugee youth in special classes. AB - OBJECTIVES: The aim of this cluster randomized trial was to evaluate the effectiveness of a school-based theatre intervention program for immigrant and refugee youth in special classes for improving mental health and academic outcomes. The primary hypothesis was that students in the theatre intervention group would report a greater reduction in impairment from symptoms compared to students in the control and tutoring groups. METHODS: Special classrooms in five multiethnic high schools were randomly assigned to theater intervention (n = 10), tutoring (n = 10) or control status (n = 9), for a total of 477 participants. Students and teachers were non-blinded to group assignment. The primary outcome was impairment from emotional and behavioural symptoms assessed by the Impact Supplement of the Strengths and Difficulties Questionnaire (SDQ) completed by the adolescents. The secondary outcomes were the SDQ global scores (teacher and youth reports), impairment assessed by teachers and school performance. The effect of the interventions was assessed through linear mixed effect models which incorporate the correlation between students in the same class, due to the nature of the randomization of the interventions by classroom. RESULTS: The theatre intervention was not associated with a greater reduction in self-reported impairment and symptoms in youth placed in special class because of learning, emotional and behavioural difficulties than a tutoring intervention or a non active control group. The estimates of the different models show a non significant decrease in both self-reported and impairment scores in the theatre intervention group for the overall group, but the impairment score decreased significantly for first generation adolescents while it increased for second generation adolescents. CONCLUSION: The difference between the population of immigrant and refugee youth newcomers studied previously and the sample of this trial may explain some of the differences in the observed impact of the theatre intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01426451. PMID- 25127252 TI - Potentially inappropriate medication use in older people with cancer: prevalence and correlates. AB - OBJECTIVES: Potentially inappropriate medication (PIM) use has been associated with an increase in adverse drug events, hospitalization and mortality. This study investigated the prevalence and factors associated with PIM use in patients presenting to a medical oncology outpatient clinic. MATERIALS AND METHODS: Consecutive patients (n=385) aged >= 70 years referred to a medical oncology outpatient clinic between January 2009 and July 2010 completed a structured data collection instrument. The instrument assessed medication use, diagnoses, self reported falls in the previous six months, pain (10-point visual analog scale [VAS]) and distress (10-point VAS). Frailty was defined using exhaustion, weight loss, Karnofsky Performance Scale, instrumental activities of daily living and physical function. PIM use was defined by the Beers Criteria. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with PIM use. RESULTS: In total, 26.5% (n=102) of the sample used >=1 PIM. The five most prevalent classes of PIMs were benzodiazepines (n=34, 8.8%), tricyclic antidepressants (n=16, 4.2%), alpha-adrenoreceptor antagonists (prazosin) (n=15, 3.9%), propulsives (metoclopramide) (n=15, 3.9%) and non steroidal anti-inflammatory drugs (n=14, 3.6%). In multivariate analyses, PIM use was associated with age 75-79 years (OR 1.83; 95%CI 1.02-3.26) compared to age 70 74 years, using >= 5 medications (OR 4.10; 95%CI 2.26-7.44) compared to <5 medications and being frail (OR 3.05; 95%CI 1.18-7.87) compared to being robust. CONCLUSION: More than one quarter of older people with cancer used one or more PIMs, and this was associated with being frail compared to being robust. PMID- 25127253 TI - Fecal carriage rates of extended-spectrum beta-lactamase-producing Escherichia coli among antibiotic naive healthy human volunteers. AB - INTRODUCTION: Higher prevalence of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli fecal carriage has been reported in the nosocomial setting than in the community. We tried to determine the fecal carriage of ESBL producing E. coli among healthy volunteers in a relatively isolated community. MATERIALS AND METHODS: This study was conducted on 115 healthy adult volunteers from whom one fecal sample was collected and was plated on selective media. Each morphotypes were identified, characterized, and ESBL phenotype was confirmed by double-disk potentiation method. Molecular characterization of ESBL gene was done using multiplex polymerase chain reaction and pulse-field gel electrophoresis (PFGE) was done to identify their clonal relation. RESULTS: ESBL-producing E. coli had a prevalence of 19% (22/115) among the healthy volunteers in the community. CTX-M was the predominant type, showed a presence 95.5% (21/22), TEM 63%, SHV 9%, and both TEM and CTX-M were present in 63.6% (14/22), all three present in 4.5% (1/22). The lineage using PFGE showed a single clone in 17 isolates. Seven isolates were type A (all TEM & CTX-M), six were type A1 (all TEM & CTX-M except 2), four were type A2 (all CTX-M), and three belonged to types B, C, and D respectively Conclusion: High prevalence rate of 19% in the community indicated by this study implies the possibility of sustained ESBL carriage even among isolated population, which could serve as a reservoir for enriching the ESBL pool in the hospital. Clonal relations also indicate a possible epidemiological source that needs to be evaluated. PMID- 25127254 TI - Epidemiological investigation of bovine tuberculosis herd breakdowns in Spain 2009/2011. AB - We analyzed the most likely cause of 687 bovine tuberculosis (bTB) breakdowns detected in Spain between 2009 and 2011 (i.e., 22% of the total number of breakdowns detected during this period). Seven possible causes were considered: i) residual infection; ii) introduction of infected cattle from other herds; iii) sharing of pastures with infected herds; iv) contiguous spread from infected neighbor herds; v) presence of infected goats in the farm; vi) interaction with wildlife reservoirs and vii) contact with an infected human. For each possible cause a decision tree was developed and key questions were included in each of them. Answers to these key questions lead to different events within each decision tree. In order to assess the likelihood of occurrence of the different events a qualitative risk assessment approach was used. For this purpose, an expert opinion workshop was organized and ordinal values, ranging from 0 to 9 (i.e., null to very high likelihood of occurrence) were assigned. The analysis identified residual infection as the most frequent cause of bTB breakdowns (22.3%; 95%CI: 19.4-25.6), followed by interaction with wildlife reservoirs (13.1%; 95%CI: 10.8-15.8). The introduction of infected cattle, sharing of pastures and contiguous spread from infected neighbour herds were also identified as relevant causes. In 41.6% (95%CI: 38.0-45.4) of the breakdowns the origin of infection remained unknown. Veterinary officers conducting bTB breakdown investigations have to state their opinion about the possible cause of each breakdown. Comparison between the results of our analysis and the opinion from veterinary officers revealed a slight concordance. This slight agreement might reflect a lack of harmonized criteria to assess the most likely cause of bTB breakdowns as well as different perceptions about the importance of the possible causes. This is especially relevant in the case of the role of wildlife reservoirs. PMID- 25127255 TI - Diversity of bacteria carried by pinewood nematode in USA and phylogenetic comparison with isolates from other countries. AB - Pine wilt disease (PWD) is native to North America and has spread to Asia and Europe. Lately, mutualistic relationship has been suggested between the pinewood nematode (PWN), Bursaphelenchus xylophilus the causal nematode agent of PWD, and bacteria. In countries where PWN occurs, nematodes from diseased trees were reported to carry bacteria from several genera. However no data exists for the United States. The objective of this study was to evaluate the diversity of the bacterial community carried by B. xylophilus, isolated from different Pinus spp. with PWD in Nebraska, United States. The bacteria carried by PWN belonged to Gammaproteobacteria (79.9%), Betaproteobacteria (11.7%), Bacilli (5.0%), Alphaproteobacteria (1.7%) and Flavobacteriia (1.7%). Strains from the genera Chryseobacterium and Pigmentiphaga were found associated with the nematode for the first time. These results were compared to results from similar studies conducted from other countries of three continents in order to assess the diversity of bacteria with associated with PWN. The isolates from the United States, Portugal and China belonged to 25 different genera and only strains from the genus Pseudomonas were found in nematodes from all countries. The strains from China were closely related to P. fluorescens and the strains isolated from Portugal and USA were phylogenetically related to P. mohnii and P. lutea. Nematodes from the different countries are associated with bacteria of different species, not supporting a relationship between PWN with a particular bacterial species. Moreover, the diversity of the bacteria carried by the pinewood nematode seems to be related to the geographic area and the Pinus species. The roles these bacteria play within the pine trees or when associated with the nematodes, might be independent of the presence of the nematode in the tree and only related on the bacteria's relationship with the tree. PMID- 25127256 TI - The X gene of adeno-associated virus 2 (AAV2) is involved in viral DNA replication. AB - Adeno-associated virus (AAV) (type 2) is a popular human gene therapy vector with a long active transgene expression period and no reported vector-induced adverse reactions. Yet the basic molecular biology of this virus has not been fully addressed. One potential gene at the far 3' end of the AAV2 genome, previously referred to as X (nt 3929 to 4393), overlapping the 3' end of the cap gene, has never been characterized, although we did previously identify a promoter just up stream (p81). Computer analysis suggested that X was involved in replication and transcription. The X protein was identified during active AAV2 replication using a polyclonal antibody against a peptide starting at amino acid 98. Reagents for the study of X included an AAV2 deletion mutant (dl78-91), a triple nucleotide substitution mutant that destroys all three 5' AUG-initiation products of X, with no effect on the cap coding sequence, and X-positive-293 cell lines. Here, we found that X up-regulated AAV2 DNA replication in differentiating keratinocytes (without helper virus, autonomous replication) and in various forms of 293 cell based assays with help from wild type adenovirus type 5 (wt Ad5) or Ad5 helper plasmid (pHelper). The strongest contribution by X was seen in increasing wt AAV2 DNA replication in keratinocytes and dl78-91 in Ad5-infected X-positive-293 cell lines (both having multi-fold effects). Mutating the X gene in pAAV-RC (pAAV-RC 3Xneg) yielded approximately a ~33% reduction in recombinant AAV vector DNA replication and virion production, but a larger effect was seen when using this same X-knockout AAV helper plasmid in X-positive-293 cell lines versus normal 293 cells (again, multi-fold). Taken together these data strongly suggest that AAV2 X encodes a protein involved in the AAV life cycle, particularly in increasing AAV2 DNA replication, and suggests that further studies are warranted. PMID- 25127257 TI - Quantifying age-related rates of social contact using diaries in a rural coastal population of Kenya. AB - BACKGROUND: Improved understanding and quantification of social contact patterns that govern the transmission dynamics of respiratory viral infections has utility in the design of preventative and control measures such as vaccination and social distancing. The objective of this study was to quantify an age-specific matrix of contact rates for a predominantly rural low-income population that would support transmission dynamic modeling of respiratory viruses. METHODS AND FINDINGS: From the population register of the Kilifi Health and Demographic Surveillance System, coastal Kenya, 150 individuals per age group (<1, 1-5, 6-15, 16-19, 20-49, 50 and above, in years) were selected by stratified random sampling and requested to complete a day long paper diary of physical contacts (e.g. touch or embrace). The sample was stratified by residence (rural-to-semiurban), month (August 2011 to January 2012, spanning seasonal changes in socio-cultural activities), and day of week. Usable diary responses were obtained from 568 individuals (~50% of expected). The mean number of contacts per person per day was 17.7 (95% CI 16.7 18.7). Infants reported the lowest contact rates (mean 13.9, 95% CI 12.1-15.7), while primary school students (6-15 years) reported the highest (mean 20.1, 95% CI 18.0-22.2). Rates of contact were higher within groups of similar age (assortative), particularly within the primary school students and adults (20-49 years). Adults and older participants (>50 years) exhibited the highest inter generational contacts. Rural contact rates were higher than semiurban (18.8 vs 15.6, p = 0.002), with rural primary school students having twice as many assortative contacts as their semiurban peers. CONCLUSIONS AND SIGNIFICANCE: This is the first age-specific contact matrix to be defined for tropical Sub-Saharan Africa and has utility in age-structured models to assess the potential impact of interventions for directly transmitted respiratory infections. PMID- 25127258 TI - Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons. AB - Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(-), and EPSC(+/-)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(-) neurons. Unlike EPSC(+) and EPSC(-) neurons, EPSC(+/-) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/-) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals. PMID- 25127260 TI - Ipilimumab treatment associated pituitary hypophysitis: clinical presentation and imaging diagnosis. AB - Ipilimumab is an immunomodulating drug for use in treatment of unresectable or metastatic melanoma with autoimmune lymphocytic hypophysitis as a reported complication. We describe three recent cases of ipilimumab associated autoimmune hypophysitis (IAH) at our institution, and provide a selected literature review showing its variable clinical presentation, imaging appearance and treatment in order to expedite early and appropriate IAH management. Patients had variable clinical presentation of hypophysitis, including headache, fatigue, visual changes, endocrinopathy, and/or hyponatremia. Contrast enhanced MRI showed symmetric pituitary gland and stalk enlargement in all of our cases and received a presumptive diagnosis of IAH. Following cessation of therapy and treatment there was normalization of pituitary morphology at follow-up MRI and return to clinical baseline. Varying clinical presentation can complicate the diagnosis of lymphocytic hypophysitis. One must be cognizant of its overall clinical and radiologic picture in patients receiving ipilimumab, now commonly used for the treatment of metastatic melanoma. PMID- 25127259 TI - Expression of stemness genes in primary breast cancer tissues: the role of SOX2 as a prognostic marker for detection of early recurrence. AB - The events leading to breast cancer (BC) progression or recurrence are not completely understood and new prognostic markers aiming at identifying high risk patients and to develop suitable therapy are highly demanded. Experimental evidences found in cancer cells a deregulated expression of some genes involved in governance of stem cell properties and demonstrated a relationship between stemness genes overexpression and poorly differentiated BC subtypes. In the present study 140 primary invasive BC specimens were collected. The expression profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT PCR were analyzed and any correlation between their expression and the BC clinic pathological features (CPfs) and prognosis was investigated. In our cohort (117 samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes negative status and higher KI67 proliferation index, respectively (p=0.019, p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004) as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035). Our study provides further proof of the suitable use of stemness genes in BC management. Interestingly, a prognostic role of SOX2, which seems to be a suitable marker of early recurrence irrespective of other clinicopathological features. PMID- 25127261 TI - Ventriculomammary shunt: an unusual ventriculoperitoneal shunt complication. AB - Ventriculoperitoneal (VP) shunt malfunctions are common and can result in significant consequences for patients. Despite the prevalence of breast augmentation surgery and breast surgery for other pathologies, few breast related VP shunt complications have been reported. A 54-year-old woman with hydrocephalus post-subarachnoid hemorrhage returned 1 month after VP shunt placement complaining of painful unilateral breast enlargement. After investigation, it was determined that the distal VP shunt catheter had migrated from the peritoneal cavity into the breast and wrapped around her breast implant. The breast enlargement was the result of cerebrospinal fluid retention. We detail this unusual case and review all breast related VP shunt complications reported in the literature. To avoid breast related complications related to VP shunt procedures, it is important to illicit pre-procedural history regarding breast implants, evade indwelling implants during catheter tunneling and carefully securing the abdominal catheter to prevent retrograde catheter migration to the breast. PMID- 25127262 TI - Identification of crypto- and neochlorogenic lactones as potent xanthine oxidase inhibitors in roasted coffee beans. AB - Xanthine oxidase (XO) inhibitory activity has been found in boiling water extracts from roasted coffee beans. Therefore, assay-guided purification of the extracts was performed using size-exclusion column chromatography, and subsequently with reversed phase HPLC to afford lactone derivatives of chlorogenic acids. Among the tested lactones, crypto- and neochlorogenic lactones showed potent XO inhibitory activities compared with three major chlorogenic acids found in coffee beans. These XO inhibitory lactones may ameliorate gout and hyperuricemia in humans who drink coffee. PMID- 25127263 TI - Making sense of the undue burden interpretation of minimal risk. PMID- 25127264 TI - On the minimal risk threshold in research with children. AB - To protect children in research, procedures that are not administered in the medical interests of a child must be restricted. The risk threshold for these procedures is generally measured according to the concept of minimal risk. Minimal risk is often defined according to the risks of "daily life." But it is not clear whose daily life should serve as the baseline; that is, it is not clear to whom minimal risk should refer. Commentators in research ethics often argue that "minimal risk" should refer to healthy children or the subjects of the research. I argue that neither of these interpretations is successful. I propose a new interpretation in which minimal risk refers to children who are not unduly burdened by their daily lives. I argue that children are not unduly burdened when they fare well, and I defend a substantive goods account of children's welfare. PMID- 25127265 TI - Justice and nontherapeutic pediatric research. PMID- 25127266 TI - Defining minimal risk and the clinical disconnect. PMID- 25127267 TI - Using the minimal risk threshold for all "no-benefit" pediatric studies. PMID- 25127268 TI - Standards for an account of children's well-being. PMID- 25127269 TI - Using the lives of children who are thriving as a baseline for minimal risk is not useful for IRB determinations. PMID- 25127270 TI - On the minimal risk threshold in research with children: "substantive goods" and other criteria. PMID- 25127271 TI - Disability, health, and minimal risk thresholds. PMID- 25127272 TI - Undue burden: looking at minimal risk and the material principle of justice. PMID- 25127273 TI - Addressing dual agency: getting specific about the expectations of professionalism. AB - Professionalism requires that physicians uphold the best interests of patients while simultaneously insuring just use of health care resources. Current articulations of these obligations like the American Board of Internal Medicine (ABIM) Foundation's Physician Charter do not reconcile how these obligations fit together when they conflict. This is the problem of dual agency. The most common ways of dealing with dual agency: "bunkering"--physicians act as though societal cost issues are not their problem; "bailing"--physicians assume that they are merely agents of society and deliver care typically based on a strongly consequentialist public health ethic; or "balancing"--a vaguely specified attempt to uphold both patient welfare and societal need for judicious resource use simultaneously--all fail. Here I propose how the problem of dual agency might begin to be addressed with rigor and consistency. Without dealing with the dual agency problem and getting more specific about how to reconcile its norms when they conflict, the expectations of professionalism risk being written off as cute, nonbinding aphorisms from the medical profession. PMID- 25127274 TI - Agency is messy: get used to it. PMID- 25127275 TI - When professional obligations collide: context matters. PMID- 25127276 TI - Legal barriers to physicians' stewardship role. PMID- 25127277 TI - In defense of bunkering. PMID- 25127278 TI - Dual agency and role morality. PMID- 25127279 TI - Getting even more specific about physicians' obligations: justice, responsibility, and professionalism. PMID- 25127280 TI - A mask tells us more than a face. PMID- 25127281 TI - Physicians' dual agency, stewardship, and marginally beneficial care. PMID- 25127282 TI - Political activism is not mandated by medical professionalism. PMID- 25127284 TI - Sox2 is a potent inhibitor of osteogenic and adipogenic differentiation in human mesenchymal stem cells. AB - Human mesenchymal stem cells (hMSCs) are a promising target for cell-based bone regeneration. However, their application for clinical use is limited because hMSCs lose their ability for cell division and differentiation during longer in vitro cultivation. The osteogenic differentiation is regulated through a complex network of molecular signal transduction pathways where the canonical Wnt pathway plays an important role. Sox2, a known key factor for maintenance of cellular pluripotency in stem cells, is supposed to influence the Wnt pathway in osteoblasts. In this study, we overexpressed Sox2 in immortalized hMSCs by lentiviral gene transfer. Sox2 overexpression significantly reduced the osteogenic and adipogenic differentiation potentials. This effect was abolished by knockdown of Sox2 overexpression. In addition, Oct4 and Nanog, other key transcription factors for pluripotency, are strongly upregulated when Sox2 is overexpressed. Furthermore, Dkk1, a target gene of the Sox2-Oct4 heterodimer and a Wnt antagonist, is downregulated. Sox2 overexpression causes higher expression levels of beta-catenin, the central transcription factor of the canonical Wnt pathway. These results suggest that Sox2 keeps hMSCs in an undifferentiated state by influencing the canonical Wnt pathway. Regulated expression of Sox2 may be a promising tool to cultivate hMSCs in sufficient quantities for cell and gene therapy applications. PMID- 25127283 TI - Local and systemic cytokine expression in patients with postherpetic neuralgia. AB - BACKGROUND: Postherpetic neuralgia (PHN) is the painful complication of a varicella zoster virus reactivation. We investigated the systemic and local gene expression of pro- and anti-inflammatory cytokine expression in patients with PHN. METHODS: Thirteen patients with PHN at the torso (Th4-S1) were recruited. Skin punch biopsies were obtained from the painful and the contralateral painless body area for intraepidermal nerve fiber density (IENFD) and cytokine profiling. Additionally, blood was withdrawn for systemic cytokine expression and compared to blood values of healthy controls. We analyzed the gene expression of selected pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha [TNF] and interleukins [IL]-1beta, IL-2, and IL-8). RESULTS: IENFD was lower in affected skin compared to unaffected skin (p<0.05), while local gene expression of pro- and anti-inflammatory cytokines did not differ except for two patients who had 7fold higher IL-6 and 10fold higher IL-10 gene expression in the affected skin compared to the contralateral unaffected skin sample. Also, the systemic expression of cytokines in patients with PHN and in healthy controls was similar. CONCLUSION: While the systemic and local expression of the investigated pro- and anti-inflammatory cytokines was not different from controls, this may have been influenced by study limitations like the low number of patients and different disease durations. Furthermore, other cytokines or pain mediators need to be considered. PMID- 25127287 TI - Gut microbiota in preterm infants with gross blood in stools: A prospective, controlled study. AB - OBJECTIVE: Gross blood in stools is a peculiar entity in preterm infants, but little is known about its etiology. As gut microbiota can be distorted in preterm infants, we aimed to evaluate the gut microbiota in infants with gross blood in stools. STUDY DESIGN: In a prospective, controlled, single-center study, we enrolled all infants born before 34 weeks of gestational age presenting gross blood in stools that was either completely isolated or associated with mild clinical symptoms or radiological signs. Each case was paired with two controls who were hospitalized in the same unit and were matched for gestational age and birth weight. The diversity of the gut microbiota was analyzed using 16S rRNA gene PCR and temporal temperature gel electrophoresis. We calculated a diversity score corresponding to the number of operational taxonomic units present in the microbiota. RESULTS: Thirty-three preterm infants with gross blood in stools were matched with 57 controls. Clinical characteristics were similar in cases and controls. There was no statistically significant difference in the diversity score between the two groups, but microbiota composition differed. The proportion of infants with Escherichia coli was significantly higher in cases than in controls (p=0.045) and the opposite pattern occurred for Staphylococcus sp. (p=0.047). CONCLUSION: Dysbiosis could be a risk factor for gross blood in stools in preterm infants. Additional, larger studies are needed to confirm the implications of the presence of different genotypes of E. coli and to evaluate preventive actions such as the prophylactic use of probiotics and/or prebiotics. PMID- 25127289 TI - Measuring behaviors of individual adolescents during group-based substance abuse intervention. AB - BACKGROUND: Group treatment is delivered in youth correctional facilities, yet groups may be iatrogenic. Few measures with demonstrated psychometric properties exist to track behaviors of individuals during groups. The authors assessed psychometrics for the Group Process-Individual Level measure (GP-IL) of group treatment. METHODS: N = 152 teens were randomized to 1 of 2 groups (10 sessions each). Adolescents, counselors, and observers rated teen behaviors at sessions 3 and 10. GP-IL assesses reinforcement for deviancy and positive behaviors, member rejection, and counselor connection and praise. RESULTS: Internal consistency and 1-month stability were demonstrated. Concurrent validity is supported by correlations with measures expected to be associated with group behavior (e.g., coping skills). Counselors and observers rated more deviancy during interactive skills-building groups versus didactic psychoeducational groups (P <= .005). Scales evidenced incremental validity. CONCLUSIONS: GP-IL offers a sound method of tracking adolescent behaviors for professionals working with groups. Counselors ratings were most reliable and valid overall. PMID- 25127290 TI - Rapid atmospheric pressure plasma jet processed reduced graphene oxide counter electrodes for dye-sensitized solar cells. AB - In this work, we present the use of reduced graphene oxide (rGO) as the counter electrode materials in dye-sensitized solar cells (DSSCs). rGO was first deposited on a fluorine-doped tin oxide glass substrate by screen-printing, followed by post-treatment to remove excessive organic additives. We investigated the effect of atmospheric pressure plasma jet (APPJ) treatment on the DSSC performance. A power conversion efficiency of 5.19% was reached when DSSCs with an rGO counter electrode were treated by APPJs in the ambient air for a few seconds. For comparison, it requires a conventional calcination process at 400 degrees C for 15 min to obtain comparable efficiency. Scanning electron micrographs show that the APPJ treatment modifies the rGO structure, which may reduce its conductivity in part but simultaneously greatly enhances its catalytic activity. Combined with the rapid removal of organic additives by the highly reactive APPJ, DSSCs with APPJ-treated rGO counter electrode show comparable efficiencies to furnace-calcined rGO counter electrodes with greatly reduced process time. This ultrashort process time renders an estimated energy consumption per unit area of 1.1 kJ/cm(2), which is only one-third of that consumed in a conventional furnace calcination process. This new methodology thus saves energy, cost, and time, which is greatly beneficial to future mass production. PMID- 25127288 TI - Associations between maternal scaffolding and executive functioning in 3 and 4 year olds born very low birth weight and normal birth weight. AB - BACKGROUND: Deficits in executive function, including measures of working memory, inhibition and cognitive flexibility, have been documented in preschoolers born very low birth weight (VLBW) compared with preschoolers born normal birth weight (NBW). Maternal verbal scaffolding has been associated with positive outcomes for both at-risk and typically developing preschoolers. AIMS: The purpose of this study was to examine associations between maternal verbal scaffolding, Verbal IQ (VIQ) and executive function measures in preschoolers born VLBW. SUBJECTS: A total of 64 VLBW and 40 NBW preschoolers ranging in age from 3 1/2 to 4 years participated in the study. OUTCOME MEASURES: VIQ was measured with the Wechsler Preschool and Primary Scale of Intelligence - Third Edition. Executive function tests included the Bear Dragon, Gift Delay Peek, Reverse Categorization and Dimensional Change Card Sort-Separated Dimensions. STUDY DESIGN: Maternal verbal scaffolding was coded during a videotaped play session. Associations between maternal verbal scaffolding and preschoolers' measures of VIQ and executive function were compared. Covariates included test age, maternal education, and gender. RESULTS: Preschoolers born VLBW performed significantly worse on VIQ and all executive function measures compared to those born NBW. Maternal verbal scaffolding was associated with VIQ for VLBW preschoolers and Gift Delay Peek for the NBW group. Girls born VLBW outperformed boys born VLBW on VIQ and Bear Dragon. CONCLUSION: Integrating scaffolding skills training as part of parent focused intervention may be both feasible and valuable for early verbal reasoning and EF development. PMID- 25127292 TI - Carbon nanotube-poly(methyl methacrylate) hybrid films: preparation using diazonium salt chemistry and mechanical properties. AB - HYPOTHESIS: The poor miscibility of carbon nanotubes (CNTs) in common organic solvents and organic monomers requires their modification by suitable functional (reactive or not) groups prior to their incorporation in thermoplastic polymers. EXPERIMENTS: Dispersion behavior of carbon nanotubes and mechanical properties of various CNT-poly(methylmethacrylate) (PMMA) nanocomposites were investigated. We studied the influence of the surface chemistry through the use of diazonium salts as an elegant and environmentally friendly platform to provide a suitable sidewall functionalization by methyl methacrylate functions. We used either a molecular size functional group through the grafting of methacryloxypropyltrimethoxysilane or a macromolecular size one, consisting in PMMA brushes grown by SI-ATRP in order to study the influence of the length of methacrylate function on the dispersion of CNT in PMMA. FINDINGS: The hardness and the elastic indentation modulus of all hybrid films were obtained through nanoindentation measurements and found to increase, using ATRP-modified CNTs, suggesting a better dispersion of CNTs in PMMA due to optimal inorganic-organic interactions promoted by the short chains of PMMA. PMID- 25127291 TI - Oil rich in carotenoids instead of vitamins C and E as a better option to reduce doxorubicin-induced damage to normal cells of Ehrlich tumor-bearing mice: hematological, toxicological and histopathological evaluations. AB - The development of therapeutic strategies to attenuate chemotherapy toxicity represents an area of great interest in cancer research, and among them is nutritional therapy based on antioxidants. As research on this topic is still controversial and scarce, we aim to investigate the effects of antioxidant supplementation with vitamin C, vitamin E or pequi oil, a carotenoid-rich oil extracted from pequi (Caryocar brasiliense), on doxorubicin (DX)-induced oxidative damage to normal cells in Ehrlich solid tumor-bearing mice. Tumor weight and volume, histopathology, morphometry and immunohistochemistry were used to assess the treatments' efficacy in containing tumor aggressiveness and regression, while possible toxicity of treatments was assessed by animals' weight, morphological analysis of the heart, liver and kidneys, hemogram, and serum levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine and urea. Although all the chemotherapeutic treatments increased internal necrosis area and reduced the positive Ki-67 cells compared to non-treated tumors, the treatments with pequi oil provided before tumor inoculation (PTDX) or in continuous and concurrent administration with doxorubicin (PTPDX) were more effective in containing tumor growth, besides increasing lymphocyte-dependent immunity and reducing the adverse side effects associated with DX-induced oxidative damage to normal cells, mainly the PTDX treatment. Vitamins C and E given before tumor inoculation and chemotherapy were not successful against doxorubicin-induced cardiotoxicity, besides increasing doxorubicin-induced nephrotoxicity, indicating that, at least for doxorubicin, pequi oil instead of vitamins C and E would be the best option to reduce its adverse effects. PMID- 25127293 TI - Synthesis and comparison of two poly (methyl methacrylate-b-3 (trimethoxysilyl)propyl methacrylate)/SiO2 hybrids by "grafting-to" approach. AB - Two copolymer/SiO2 hybrids are prepared by growing SiO2 on the template of well structured diblock copolymer PMMA-b-PMPS using a "grafting-to" approach. PMMA-b PMPS is obtained by atom transfer radical polymerization (ATRP) of methyl methacrylate (PMMA) and 3-(trimethoxysilyl)propyl methacrylate (PMPS) using a brominated initiator end group termed 1H,1H,2H,2H-heptadecafluoro (F-Br) and a conventional initiator of ethyl 2-bromoisobutyrate (EBiB), respectively. The "grafting-to" approach is controlled at HCl for 24h by hydrolysis and condensation of Si(OCH3)3 groups in PMPS with tetraethyl orthosilicate (TEOS) to gain both hybrids of F-PMMA-b-PMPS/SiO2 (by F-Br initiator) and E-PMMA-b PMPS/SiO2 (by EBIB initiator). Comparatively, a little amount of fluorine content provided by F-Br is able to tighten the size of self-assembled micelles, to improve wettability and the viscoelasticity of F-PMMA-b-PMPS film due to F-Br migrating onto the film surface. Therefore, the surface of F-PMMA-b-PMPS film is sufficiently hydrophobic (99 degrees and Deltaf=2941Hz) than E-PMMA-b-PMPS film (94 degrees and Deltaf=4820Hz), and the viscoelasticity of the adsorbed layer for F-PMMA-b-PMPS (DeltaD/Deltaf=-0.112) film is much harder than E-PMMA-b-PMPS/SiO2 (DeltaD/Deltaf=-0.071). On the other hand, the cross-linked silica in PMMA-b PMPS/SiO2 could also increase water contact angels of films (100-107 degrees ) and decrease the water absorption (Deltaf=704-798Hz). The influence on the viscoelasticity of the adsorbed layer by the fluorine group is much more obvious than the cross-linked silica, therefore F-PMMA-b-PMPS/SiO2 (DeltaD/Deltaf=-0.347) and F-PMMA-b-PMPS (DeltaD/Deltaf=-0.112) films have harder adsorbed layer than E PMMA-b-PMPS/SiO2 (-0.071) and F-PMMA-b-PMPS films (-0.042). However, compared with a slightly improvement in thermo stability by F-Br, the cross-linked silica in PMMA-b-PMPS/SiO2 performs significantly improving thermal decomposition temperature at 300 degrees C and 350 degrees C. PMID- 25127294 TI - Self-assembled monolayers of mercaptobenzoic acid and magnetite nanoparticles as an efficient support for development of tuberculosis genosensor. AB - In this work, a genosensor for the electrochemical detection of genomic DNA from Mycobacterium tuberculosis was developed. The biosensor is based on self assembled monolayers of mercaptobenzoic acid (MBA) and magnetite nanoparticles (Fe3O4Nps) on bare gold electrode for immobilization of DNA probe. The aim of this work was the development of a platform based on cysteine-coated magnetic Fe3O4Nps linked via the carboxylate group from MBA to the work electrode surface and subsequently to the DNA probe. The probe-genome interaction was evaluated using a [Fe(CN)6](4-)/[Fe(CN)6](3-) redox pair. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to evaluate the bioelectrochemical behavior of the sensor. Atomic force microscopy images showed Fe3O4Nps immobilized across the electrode surface. The interaction of the sensor with different genome DNA concentrations resulted in changes in the charge transfer resistance, indicating a possible use for tuberculosis detection at low concentrations (detection limit of 6ngMUL(-1)). PMID- 25127295 TI - Catalytic performance of activated carbon supported cobalt catalyst for CO2 reforming of CH4. AB - Syngas production by CO2 reforming of CH4 in a fixed bed reactor was investigated over a series of activated carbon (AC) supported Co catalysts as a function of Co loading (between 15 and 30wt.%) and calcination temperature (Tc=300, 400 or 500 degrees C). The catalytic performance was assessed through CH4 and CO2 conversions and long-term stability. XRD and SEM were used to characterize the catalysts. It was found that the stability of Co/AC catalysts was strongly dependent on the Co loading and calcination temperature. For the loadings (25wt.% for Tc=300 degrees C), stable activities have been achieved. The loading of excess Co (>wt.% 25) causes negative effects not only on the performance of the catalysts but also on the support surface properties. In addition, the experiment showed that ultrasound can enhance and promote dispersion of the active metal on the carrier, thus improving the catalytic performance of the catalyst. The catalyst activity can be long-term stably maintained, and no obvious deactivation has been observed in the first 2700min. After analyzing the characteristics, a reaction mechanism for CO2 reforming of CH4 over Co/AC catalyst was proposed. PMID- 25127296 TI - A green one-pot synthesis of Pt/TiO2/Graphene composites and its electro-photo synergistic catalytic properties for methanol oxidation. AB - A facile and green one-pot method was used to synthesize Pt/TiO2/Graphene composites with ethanol as a reducing agent under microwave irradiation. The as prepared composites were characterized by SEM, TEM, EDX, XPS, XRD and Raman. Electrocatalytic performance of the Pt/TiO2/GNs composites was investigated by cyclic voltammetry (CV), chronoamperometric (CA), COad stripping voltammetry and electrochemical impedance spectrum (EIS). All experimental data have revealed that TiO2 (P25) not only enhanced the reduction ability of ethanol under microwave irradiation but also promoted Pt heterogeneous nucleation to form Pt nanoclusters which are around P25 and loaded on graphene nanosheets (GNs) surface. Electrochemical experiments showed that Pt/TiO2/GNs had much higher catalytic activity and stability toward methanol oxidation reaction (MOR) and better resistance to CO poisoning compared with Pt/GNs and the commercially available Johnson Matthey 20% Pt/C catalyst (Pt/C-JM). Especially under UV irradiation with 20min, Pt/TiO2/GNs composites showed an ultrahigh forward peak current density of 1354mAmg(-1), nearly 2.5 times higher than that of Pt/C-JM, which indicated that the electrocatalytic and photocatalytic properties of Pt/TiO2/GNs had been integrated to boost the catalytic performance for MOR. PMID- 25127297 TI - Role of proprioceptive information to control balance during gait in healthy and hemiparetic individuals. AB - Proprioceptive information is important for balance control yet little is known about how it is used during gait or how a stroke affects its use. The aim of this study was to evaluate the role of proprioception in controlling balance during gait in healthy participants and after stroke. Twelve healthy and 9 hemiparetic participants walked on an instrumented treadmill in a fully lit room, while whole body, three-dimensional kinematics were quantified. Vibration was applied continuously or during the stance phase only, on the posterior neck muscles and triceps surae tendon on the non-dominant/paretic side. Difficulty in maintaining dynamic and postural balance was evaluated using stabilizing and destabilizing forces, respectively. Continuous and stance phase vibration of the triceps surae reduced the difficulty in maintaining both dynamic and postural balance in healthy participants (p<.05), with a greater distance between the center of pressure and the limit of the potential base of support, a more backward body position, and no change in spatio-temporal gait parameters. No effect of neck muscle vibration was observed on balance (p=.63 and above). None of the vibration conditions affected balance or gait parameters among stroke participants. The results confirmed that proprioceptive information was not used to control balance during gait in stroke participants. The importance of proprioceptive information may depend on other factors such as walking and visual conditions. Changes in sensory integration ability likely explain the results after stroke. Further study is needed to understand the integration of proprioceptive and visual information to control balance during gait after stroke. PMID- 25127298 TI - Hydrogen bond disruption in DNA base pairs from (14)C transmutation. AB - Recent ab initio molecular dynamics simulations have shown that radioactive carbon does not normally fragment DNA bases when it decays. Motivated by this finding, density functional theory and Bader analysis have been used to quantify the effect of C -> N transmutation on hydrogen bonding in DNA base pairs. We find that (14)C decay has the potential to significantly alter hydrogen bonds in a variety of ways including direct proton shuttling (thymine and cytosine), thermally activated proton shuttling (guanine), and hydrogen bond breaking (cytosine). Transmutation substantially modifies both the absolute and relative strengths of the hydrogen bonding pattern, and in two instances (adenine and cytosine), the density at the critical point indicates development of mild covalent character. Since hydrogen bonding is an important component of Watson Crick pairing, these (14)C-induced modifications, while infrequent, may trigger errors in DNA transcription and replication. PMID- 25127299 TI - Emphysema genetics. Location, location, location! PMID- 25127300 TI - New asthma biomarkers: shorter telomeres, longer disease? PMID- 25127301 TI - The child is father of the man? PMID- 25127302 TI - ICU-acquired weakness, morbidity, and death. PMID- 25127303 TI - Propensity-matching analysis is not straightforward. PMID- 25127304 TI - Measuring mucociliary transport and mucus properties in multiple regions of airway epithelial surfaces helps clarify cystic fibrosis defects. PMID- 25127305 TI - Improvement of sinus disease in cystic fibrosis with ivacaftor therapy. PMID- 25127306 TI - In vivo X-ray imaging reveals improved airway surface hydration after a therapy designed for cystic fibrosis. PMID- 25127307 TI - Osteopontin and periostin are associated with a 20-year decline of pulmonary function in patients with asthma. PMID- 25127308 TI - Insulin resistance, puberty, and nonatopic asthma in adolescent girls. PMID- 25127309 TI - Asthmatic and normal respiratory epithelial cells respond differently to mechanical apical stress. PMID- 25127310 TI - Inhaled antibiotics or inhaled hazard? PMID- 25127311 TI - Reply: inhaled antibiotics or inhaled hazard? PMID- 25127312 TI - Small lesion, severe consequences. An intriguing ventilation-perfusion scintigraphy. PMID- 25127313 TI - Pulmonary arteriovenous malformations in the setting of pulmonary amyloidosis. PMID- 25127314 TI - Sleep-disordered breathing in pregnancy. PMID- 25127315 TI - Hydrogen-bond-dynamics-based switching of conductivity and magnetism: a phase transition caused by deuterium and electron transfer in a hydrogen-bonded purely organic conductor crystal. AB - A hydrogen bond (H-bond) is one of the most fundamental and important noncovalent interactions in chemistry, biology, physics, and all other molecular sciences. Especially, the dynamics of a proton or a hydrogen atom in the H-bond has attracted increasing attention, because it plays a crucial role in (bio)chemical reactions and some physical properties, such as dielectricity and proton conductivity. Here we report unprecedented H-bond-dynamics-based switching of electrical conductivity and magnetism in a H-bonded purely organic conductor crystal, kappa-D3(Cat-EDT-TTF)2 (abbreviated as kappa-D). This novel crystal kappa-D, a deuterated analogue of kappa-H3(Cat-EDT-TTF)2 (abbreviated as kappa H), is composed only of a H-bonded molecular unit, in which two crystallographically equivalent catechol-fused ethylenedithiotetrathiafulvalene (Cat-EDT-TTF) skeletons with a +0.5 charge are linked by a symmetric anionic [O...D...O](-1)-type strong H-bond. Although the deuterated and parent hydrogen systems, kappa-D and kappa-H, are isostructural paramagnetic semiconductors with a dimer-Mott-type electronic structure at room temperature (space group: C2/c), only kappa-D undergoes a phase transition at 185 K, to change to a nonmagnetic insulator with a charge-ordered electronic structure (space group: P1). The X-ray crystal structure analysis demonstrates that this dramatic switching of the electronic structure and physical properties originates from deuterium transfer or displacement within the H-bond accompanied by electron transfer between the Cat-EDT-TTF pi-systems, proving that the H-bonded deuterium dynamics and the conducting TTF pi-electron are cooperatively coupled. Furthermore, the reason why this unique phase transition occurs only in kappa-D is qualitatively discussed in terms of the H/D isotope effect on the H-bond geometry and potential energy curve. PMID- 25127316 TI - Postpartum Maternal Sleep, Maternal Depressive Symptoms and Self-Perceived Mother Infant Emotional Relationship. AB - This study examined the links between maternal sleep, maternal depressive symptoms, and mothers' perceptions of their emotional relationship with their infant in a self-recruited sample of mothers. Eighty mothers of infants 3-18 months old completed sleep diaries for 5 consecutive nights, and questionnaires assessing sleep (Insomnia Severity Index [ISI]), depressive symptom severity (Edinburgh Postnatal Depression Scale [EPDS]), and perceived mother-infant relationship (Postpartum Bonding Questionnaire [PBQ] and Maternal Postnatal Attachment Questionnaire [MPAQ]). Significant correlations, controlling for depression severity, were found between more disturbed maternal sleep and more negative maternal perceptions of the mother-infant relationship. Regression analyses revealed that EPDS showed the strongest association with PBQ, whereas ISI demonstrated the strongest association with MPAQ. The present study highlights the importance of deepening and expanding our understanding of the negative implications of maternal sleep problems. PMID- 25127317 TI - Belizentrin, a highly bioactive macrocycle from the dinoflagellate Prorocentrum belizeanum. AB - Belizentrin (1), a novel 25-membered polyketide-derived macrocycle, was isolated from cultures of the marine dinoflagellate Prorocentrum belizeanum. This metabolite is the first member of an unprecedented class of polyunsaturated and polyhydroxylated macrolactams. The structure of 1 was primarily determined by NMR and computational methods. Pharmacological assays with cerebellar cells showed that 1 produces important changes in neuronal network integrity at nanomolar concentrations. PMID- 25127319 TI - Potential energy surfaces and quasiclassical trajectory study of the O + H2(+)-> OH(+) + H, OH + H(+) proton and hydrogen atom transfer reactions and isotopic variants (D2(+), HD(+)). AB - The rate constants (k; T: 200-900 K) and cross-sections (sigma; Ecol: 0.010-0.50 eV) of the O + H2(+)-> OH(+) + H (1), OH + H(+) (2) reactions, which occur on the ground (1(2)A'') and first excited (1(2)A') potential energy surfaces (PESs), respectively, were investigated for the first time, considering also the rate constants for D2(+) and HD(+). Ab initio multireference configuration interaction calculations were performed on both barrierless PESs (where the minimum energy path involves the insertion of the O atom into the middle of the H2(+) bond), and suitable analytical expressions were developed for the first time and used in quasiclassical trajectory (QCT) calculations. k(1) ~ 3k(2) independent of the isotopic variant, k(H2(+)) > k(HD(+)) > k(D2(+)) for , and the intermolecular and intramolecular isotopic effects are essentially independent of T. Comparison with the Langevin-Gioumousis-Stevenson (LGS) simple capture model shows that these results are similar to the QCT ones, especially for ; and the isotopic effects are coincident with the QCT ones for both reactions. For O + H2(+), sigma(1) ~ 3sigma(2) at Ecol<= 0.10 eV, and sigma(1) = 1.5sigma(2) at 0.40 and 0.50 eV. The larger value of sigma(1(2)A'') with respect to sigma(1(2)A') arises from the larger value of bmax(1(2)A'') with respect to bmax(1(2)A'), and this results from the more attractive character of the former PES. Besides, the reaction probabilities are quite large [0.78-0.98 (1(2)A'') and 0.78-0.93 (1(2)A')], and the decreasing trend of both cross-sections as Ecol increases arises from the barrierless character of both PESs. We expect that these results (in particular, the competition between proton transfer and hydrogen atom transfer) will encourage experimentalists to carry out investigations on this interesting reaction. PMID- 25127318 TI - Hypnosis in Spain (1888-1905): from spectacle to medical treatment of mediumship. AB - Towards the end of the nineteenth century, some Spanish physicians sought to legitimize hypnotherapy within medicine. At the same time, hypnotism was being popularized among the Spanish population through stage hypnosis shows. In order to extend the use of medical hypnotherapy, some physicians made efforts to demarcate the therapeutic use of hypnotic suggestion from its application for recreational purposes, as performed by stage hypnotists. However, in the eyes of some physicians, the first public session to legitimize hypnotherapy turned out to be a complete failure due to its similarities with a stage hypnosis performance. Apart from exploring this kind of hitherto little-known historical cases, we explore the role of spiritists in legitimizing medical hypnosis. At a time when Spanish citizens were still reluctant to accept hypnotherapy, the spiritists sponsored a charitable clinic where treatment using hypnosis was offered. We conclude that the clinic was effective in promoting the use of hypnotherapy, both among physicians as clinical practice, and as a medical treatment for patients from the less privileged classes of Spanish society. PMID- 25127321 TI - Evaluation of noise reduction methods for sentence recognition by Mandarin speaking cochlear implant listeners. AB - OBJECTIVES: The purpose of this study was to (1) assess the contributions of single-channel noise-reduction (NR) algorithms for improving speech intelligibility for Mandarin-speaking cochlear implant (CI) listeners and (2) examine whether different algorithms perform differently in various environmental noises. DESIGN: Mandarin sentences were corrupted by three types of maskers, including speech-shaped noise, babble, and car noise, at +10, +5, or 0 dB signal to noise ratios and processed by four single-channel NR algorithms. The processed sentences were played to seven Mandarin-speaking CI patients for recognition. All patients used their own clinical speech processors in the testing. RESULTS: Significant improvements in speech intelligibility were observed with most noise suppression methods. Further analysis indicated that NR algorithms could effectively preserve the phonetic boundaries, which are critical for speech perception, and also the fundamental frequency (F0) representation was moderately improved by the NR methods. CONCLUSIONS: The present study demonstrated that although most single-channel NR algorithms could effectively improve speech recognition in noise for Mandarin-speaking CI listeners, these algorithms perform differently in various environmental noises, and it would be beneficial for the CI sound processor to integrate NR methods tailored to individual types of noises for the best cost and benefit tradeoff. In addition, the intelligibility improvement may be attributed to the restoration of acoustic landmark information and the improved representation of temporal F0 cues. PMID- 25127320 TI - Hearing function in patients living with HIV/AIDS. AB - OBJECTIVES: During the earlier years of the HIV/AIDS epidemic, initial reports described sensorineural hearing loss in up to 49% of individuals with HIV/AIDS. During those years, patients commonly progressed to advanced stages of HIV disease and frequently had neurological complications. However, the abnormalities on pure-tone audiometry and brainstem-evoked responses outlined in small studies were not always consistently correlated with advanced stages of HIV/AIDS. Moreover, these studies could not exclude the confounding effect of concurrent opportunistic infections and syphilis. Additional reports also have indicated that some antiretroviral medications may be ototoxic; thus, it has been difficult to make conclusions regarding the cause of changes in hearing function in HIV infected patients. More recently, accelerated aging has been suggested as a potential explanation for the disproportionate increase in complications of aging described in many HIV-infected patients; hence, accelerated aging-associated hearing loss may also be playing a role in these patients. DESIGN: We conducted a large cross-sectional analysis of hearing function in over 300 patients with HIV 1 infection and in 137 HIV-uninfected controls. HIV-infected participants and HIV uninfected controls underwent a 2-hr battery of hearing tests including the Hearing Handicap Inventory, standard audiometric pure-tone air and bone conduction testing, tympanometric testing, and speech reception and discrimination testing. RESULTS: Three-way analysis of variance (ANOVA) and logistic regression analysis of 278 eligible HIV-infected subjects stratified by disease stage in early HIV disease (n = 127) and late HIV disease (n = 148) and 120 eligible HIV-uninfected controls revealed no statistically significant differences among the three study groups in either overall 4-frequency pure-tone average (4-PTA) or hearing loss prevalence in either ear. Three-way ANOVA showed significant differences in word recognition scores in the right ear among groups, a significant group effect on tympanogram static admittance in both ears and a significant group effect on tympanic gradient in the right ear. There was significantly larger admittance and gradient in controls as compared to the HIV infected group at late stage of disease. Hearing loss in the HIV-infected groups was associated with increased age and was similar to that described in the literature for the general population. Three-way ANOVA analysis also indicated significantly greater pure-tone thresholds (worse hearing) at low frequencies in HIV patients in the late stage of disease compared with HIV-uninfected controls. This difference was also found by semi-parametric mixed effects models. CONCLUSIONS: Despite reports of "premature" or "accelerated" aging in HIV infected subjects, we found no evidence of hearing loss occurring at an earlier age in HIV-infected patients compared to HIV-uninfected controls. Similar to what is described in the general population, the probability of hearing loss increased with age in the HIV-infected subjects and was more common in patients over 60 years of age. Interestingly, HIV-infected subjects had worse hearing at lower frequencies and have significant differences in tympanometry compared to HIV uninfected controls; these findings deserve further study. PMID- 25127322 TI - Interaural level differences and sound source localization for bilateral cochlear implant patients. AB - OBJECTIVES: The aims of this study were (i) to determine the magnitude of the interaural level differences (ILDs) that remain after cochlear implant (CI) signal processing and (ii) to relate the ILDs to the pattern of errors for sound source localization on the horizontal plane. DESIGN: The listeners were 16 bilateral CI patients fitted with MED-EL CIs and 34 normal-hearing listeners. The stimuli were wideband, high-pass, and low-pass noise signals. ILDs were calculated by passing signals, filtered by head-related transfer functions (HRTFs) to a Matlab simulation of MED-EL signal processing. RESULTS: For the wideband signal and high-pass signals, maximum ILDs of 15 to 17 dB in the input signal were reduced to 3 to 4 dB after CI signal processing. For the low-pass signal, ILDs were reduced to 1 to 2 dB. For wideband and high-pass signals, the largest ILDs for +/-15 degree speaker locations were between 0.4 and 0.7 dB; for the +/-30 degree speaker locations between 0.9 and 1.3 dB; for the 45 degree speaker locations between 2.4 and 2.9 dB; for the +/-60 degree speaker locations, between 3.2 and 4.1 dB; and for the +/-75 degree speaker locations between 2.7 and 3.4 dB. All of the CI patients in all the stimulus conditions showed poorer localization than the normal-hearing listeners. Localization accuracy for the CI patients was best for the wideband and high-pass signals and was poorest for the low-pass signal. CONCLUSIONS: Localization accuracy was related to the magnitude of the ILD cues available to the normal-hearing listeners and CI patients. The pattern of localization errors for the CI patients was related to the magnitude of the ILD differences among loudspeaker locations. The error patterns for the wideband and high-pass signals, suggest that, for the conditions of this experiment, patients, on an average, sorted signals on the horizontal plane into four sectors-on each side of the midline, one sector including 0, 15, and possibly 30 degree speaker locations, and a sector from 45 degree speaker locations to 75 degree speaker locations. The resolution within a sector was relatively poor. PMID- 25127323 TI - Automated screening for high-frequency hearing loss. AB - OBJECTIVE: Hearing loss at high frequencies produces perceptual difficulties and is often an early sign of a more general hearing loss. This study reports the development and validation of two new speech-based hearing screening tests in English that focus on detecting hearing loss at frequencies above 2000 Hz. DESIGN: The Internet-delivered, speech-in noise tests used closed target-word sets of digit triplets or consonant-vowel-consonant (CVC) words presented against a speech-shaped noise masker. The digit triplet test uses the digits 0 to 9 (excluding the disyllabic 7), grouped in quasi-random triplets. The CVC test uses simple words (e.g., "cat") selected for the high-frequency spectral content of the consonants. During testing, triplets or CVC words were identified in an adaptive procedure to obtain the speech reception threshold (SRT) in noise. For these new, high-frequency (HF) tests, the noise was low-pass filtered to produce greater masking of the low-frequency speech components, increasing the sensitivity of the test for HF hearing loss. Individual test tokens (digits, CVCs) were first homogenized using a group of 10 normal-hearing (NH) listeners by equalizing intelligibility across tokens at several speech-in-noise levels. Both tests were then validated and standardized using groups of 24 NH listeners and 50 listeners with hearing impairment. Performance on the new high frequency digit triplet (HF-triplet) and CVC (HF-CVC) tests was compared with audiometric hearing loss, and with that on the unfiltered, broadband digit triplet test (BB-triplet) test, and the ASL (Adaptive Sentence Lists) speech-in-noise test. RESULTS: The HF triplet and HF-CVC test results (SRT) both correlated positively and highly with high-frequency audiometric hearing loss and with the ASL test. SRT for both tests as a function of high-frequency hearing loss increased at nearly three times the rate as that of the BB-triplet test. The intraindividual variability (SD) on the tests was about 2.1 (HF-triplet) and 1.7 (HF-CVC) times less than that for the BB triplet test. The effect on the HF-triplet test of varying presentation method (professional or cheap headphones and loudspeakers) was small for the NH group and somewhat larger, but nonsignificant for the hearing-impaired group. Test repetition produced a moderate, significant learning effect for the first and second retests, but was small and nonsignificant for further retesting. The learning effect was about two times larger for the HF-CVC test than for the HF triplet test. The sensitivity of both new tests for high-frequency hearing loss was similar, with an 87% true-positive and 7% false-positive ratio for detecting an average high-frequency hearing loss of 20 dB or more. CONCLUSIONS: The new HF triplet and HF-CVC tests provide a sensitive and accurate method for detecting high-frequency hearing loss. The tests may signal developing hearing impairment at an early stage. The HF-triplet is preferred over the HF-CVC test because of its smaller learning effect, smaller error rate, greater simplicity, and lower cultural dependency. PMID- 25127325 TI - FS4, FS4-p, and FSP: a 4-month crossover study of 3 fine structure sound-coding strategies. AB - OBJECTIVES: The aim of the present study was to compare two novel fine structure strategies "FS4" and "FS4-p" with the established fine structure processing (FSP) strategy. FS4 provides fine structure information on the apical four-electrode channels. With FS4-p, these electrodes may be stimulated in a parallel manner. The authors evaluated speech perception, sound quality, and subjective preference. DESIGN: A longitudinal crossover study was done on postlingually deafened adults (N = 33) who were using FSP as their default strategy. Each participant was fitted with FS4, FS4-p, and FSP, for 4 months in a randomized and blinded order. After each run, an Adaptive Sentence test in noise (Oldenburger Sentence Test [OLSA]) and a Monosyllable test in quiet (Freiburger Monosyllables) were performed, and subjective sound quality was determined with a Visual Analogue Scale. At the end of the study the preferred strategy was noted. RESULTS: Scores of the OLSA did not reveal any significant differences among the three strategies, but the Freiburger test showed a statistically significant effect (p = 0.03) with slightly worse scores for FS4 (49.7%) compared with FSP (54.3%). Performance of FS4-p (51.8%) was comparable with the other strategies. Both audiometric tests depicted a high variability among subjects. The number of best-performing strategies for each participant individually was as follows: (a) for the OLSA: FSP, N = 10.5; FS4, N = 10.5; and FS4-p, N = 12; and (b) for the Freiburger test: FSP, N = 14; FS4, N = 9; and FS4-p, N = 10. A moderate agreement was found in the best-performing strategies of the Speech tests within the participants. For sound quality, speech in quiet, classical, and pop music were assessed. No significant effects of strategy were found for speech in quiet and classical music, but auditory impression of pop music was rated as more natural in FSP compared with FS4 (p = 0.04). It is interesting that at the end of the study, a majority of the participants favored the new coding strategies over their previous default FSP (FSP, N = 13; FS4, N = 13; FS4-p, N = 7). CONCLUSIONS: In summary, FS4 and FS4-p offer new and further options in audio processor fitting, with similar levels of speech understanding in noise as FSP. This is an interesting result, given that the strategies' presentation of temporal fine structure differs from FSP. At the end of the study, 20 of 33 subjects chose either FS4 or FS4-p over their previous default strategy FSP. PMID- 25127324 TI - Evaluation of ototoxicity in patients treated with hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin and sodium thiosulfate. AB - OBJECTIVES: Ototoxic hearing loss associated with intravenous or intra-arterial administration of cisplatin is well documented. However, there is limited data regarding the ototoxic effect of cisplatin when perfused into the abdominal cavity using hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this study is to assess and describe ototoxicity in patients treated with HIPEC with cisplatin and sodium thiosulfate for peritoneal surface malignancies. DESIGN: We performed a retrospective chart review (2007-2012) of patients treated for advanced peritoneal malignancies at a tertiary care center using HIPEC with cisplatin and sodium thiosulfate infusion. Thirteen patients (12 males, 1 female) met study criteria. Audiometric thresholds were compared before and after treatment. A 20 dB loss at any single frequency, 10 dB decrease at any two adjacent frequencies, or loss of response at three consecutive test frequencies defined a significant ototoxic change (). RESULTS: Despite minimal hearing change in six patients, none of the 13 patients in our study exhibited a significant ototoxic change in hearing sensitivity post HIPEC with cisplatin at any test interval in any test frequency. CONCLUSIONS: Our findings represent the first objective assessment of ototoxic effect after HIPEC with cisplatin and sodium thiosulfate infusion. Our results suggest that peritoneal perfusion of cisplatin with intravenous perfusion of sodium thiosulfate is not associated with ototoxic changes in hearing sensitivity. Further investigation of the administration and systemic mechanism of absorption of sodium thiosulfate as a potential protection against cisplatin ototoxicity is needed to confirm these findings. PMID- 25127326 TI - Is "no response" on diagnostic auditory brainstem response testing an indication for cochlear implantation in children? AB - OBJECTIVES: To compare the results of a "no response" (NR) result on auditory brainstem response (ABR) testing with those of behavioral pure-tone audiometry and ultimate clinical tracking to cochlear implantation (CI). DESIGN: Retrospective review of pediatric patients who underwent multifrequency ABR testing in a 5 year span. Total of 1143 pediatric patients underwent ABR testing during the study period and 105 (9.2%) were identified with bilateral NR based on absent responses to both click and tone burst stimuli. For the children with NR, various clinical parameters were evaluated as these children progressed through the CI evaluation process. Children were grouped based on whether they underwent ABRs for diagnostic or for confirmatory purposes. RESULTS: Of the 105 children who met inclusion criteria, 94 had sufficient follow-up to be included in this analysis. Ninety-one (96.8%) of 94 children with bilateral NR ABRs were ultimately recommended for and received a CI. Three (3.2%) children were not recommended for implantation based on the presence of multiple comorbidities rather than auditory factors. None of the children (0%) had enough usable residual hearing to preclude CI. For those who had diagnostic ABRs, the average time at ABR testing was 5.4 months (SD 6.2, range 1-36) and the average time from ABR to CI was 10.78 months (SD 5.0, range 3-38). CONCLUSIONS: CI should tentatively be recommended for children with a bilateral NR result with multifrequency ABR, assuming confirmatory results with behavioral audiometric testing. Amplification trials, counseling, and auditory-based intervention therapy should commence but not delay surgical intervention, as it does not appear to change the eventual clinical course. Children not appropriate for this "fast-tracking" to implantation might include those with significant comorbidities, auditory neuropathy spectrum disorder, and unreliable or poorly correlated results on behavioral audiometric testing. PMID- 25127327 TI - Intelligibility of emotional speech in younger and older adults. AB - OBJECTIVES: Little is known about the influence of vocal emotions on speech understanding. Word recognition accuracy for stimuli spoken to portray seven emotions (anger, disgust, fear, sadness, neutral, happiness, and pleasant surprise) was tested in younger and older listeners. Emotions were presented in either mixed (heterogeneous emotions mixed in a list) or blocked (homogeneous emotion blocked in a list) conditions. Three main hypotheses were tested. First, vocal emotion affects word recognition accuracy; specifically, portrayals of fear enhance word recognition accuracy because listeners orient to threatening information and/or distinctive acoustical cues such as high pitch mean and variation. Second, older listeners recognize words less accurately than younger listeners, but the effects of different emotions on intelligibility are similar across age groups. Third, blocking emotions in list results in better word recognition accuracy, especially for older listeners, and reduces the effect of emotion on intelligibility because as listeners develop expectations about vocal emotion, the allocation of processing resources can shift from emotional to lexical processing. DESIGN: Emotion was the within-subjects variable: all participants heard speech stimuli consisting of a carrier phrase followed by a target word spoken by either a younger or an older talker, with an equal number of stimuli portraying each of seven vocal emotions. The speech was presented in multi-talker babble at signal to noise ratios adjusted for each talker and each listener age group. Listener age (younger, older), condition (mixed, blocked), and talker (younger, older) were the main between-subjects variables. Fifty-six students (Mage= 18.3 years) were recruited from an undergraduate psychology course; 56 older adults (Mage= 72.3 years) were recruited from a volunteer pool. All participants had clinically normal pure-tone audiometric thresholds at frequencies <=3000 Hz. RESULTS: There were significant main effects of emotion, listener age group, and condition on the accuracy of word recognition in noise. Stimuli spoken in a fearful voice were the most intelligible, while those spoken in a sad voice were the least intelligible. Overall, word recognition accuracy was poorer for older than younger adults, but there was no main effect of talker, and the pattern of the effects of different emotions on intelligibility did not differ significantly across age groups. Acoustical analyses helped elucidate the effect of emotion and some intertalker differences. Finally, all participants performed better when emotions were blocked. For both groups, performance improved over repeated presentations of each emotion in both blocked and mixed conditions. CONCLUSIONS: These results are the first to demonstrate a relationship between vocal emotion and word recognition accuracy in noise for younger and older listeners. In particular, the enhancement of intelligibility by emotion is greatest for words spoken to portray fear and presented heterogeneously with other emotions. Fear may have a specialized role in orienting attention to words heard in noise. This finding may be an auditory counterpart to the enhanced detection of threat information in visual displays. The effect of vocal emotion on word recognition accuracy is preserved in older listeners with good audiograms and both age groups benefit from blocking and the repetition of emotions. PMID- 25127328 TI - Long-term hearing deficits after childhood middle ear disease. AB - OBJECTIVES: To investigate the long-term impact of childhood otitis media on listening ability in school-aged children. DESIGN: Speech perception in background noise was measured in two groups of 35 children, aged 6 to 12 years, with normal middle ear function and sound detection at assessment. The first consisted of children who had previously suffered middle ear disease; the second those with no history of middle ear disease. RESULTS: Binaural speech perception ability was significantly poorer in the children with prior middle ear disease. Furthermore, spatial listening (the ability to selectively attend to a sound signal from one location) was also significantly impaired. Significant correlations were demonstrated between both the age of onset and the duration of childhood otitis media and speech perception ability (onset: r = -0.58, p < 0.001; duration: r = -0.63, p < 0.001). CONCLUSIONS: These results demonstrate the risk of long-term functional hearing deficit for children with middle ear disease history in childhood. They also indicate that this risk is increased with earlier onset and longer duration. The findings highlight the need for early intervention and an awareness of the potential for reduced functional listening ability even after sound detection has returned to normal. PMID- 25127330 TI - The SOX transcription factors as key players in pluripotent stem cells. AB - Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), and induced PSCs (iPSCs) are able to self-renew and differentiate into a multitude of specialized cellular lineages. In these cells, the pluripotential identity is maintained by a group of transcription factors (TFs). Among these factors, SOX TFs play an essential role, not only in regulating pluripotency but also in mediating self-renewal and differentiation. Some SOX TFs are highly expressed in undifferentiated PSCs, while others are upregulated upon differentiation to promote specific lineage differentiation. Further roles of SOX factors in pluripotency are highlighted through their critical involvement in iPSCs generation. To perform these multiple functions and activities, SOX TFs are strongly associated with a complex regulatory network(s) that involves the binding of SOX factors to variant trans-acting partners to activate or suppress specific genes. Although, SOX2 has attracted special attention as a critical factor in maintaining PSCs characteristics and as an integral component that is required to reprogram somatic cells into pluripotency, new reports widely appreciated that other SOX TFs, such as SOX1, SOX3, or reengineered SOX7 and SOX17, can compensate for the absence of SOX2 and thus play a fundamental role during the reprogramming process and maintaining pluripotency. These findings indicate that the recent progress has greatly expanded our knowledge about the role of SOX factors in PSCs. Thus, in this review we summarize what is currently known about the roles of SOX factors in PSCs and their role in somatic cell reprogramming. Also, we intend to provide an update on their relationship with other factors in regulating the characteristics and early differentiation of PSCs. PMID- 25127329 TI - Studying progression from glucose intolerance to type 2 diabetes in obese children. AB - AIM: Identification of metabolic and genetic factors capable to mediate progression from normal glucose tolerance (NGT) through impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in childhood obesity. PATIENTS AND METHODS: Three groups of obese children with NGT (n=54), IGT (n=35), and T2D (n=62) were evaluated. A control group of non-obese normal children (n=210) was also studied. In obese patients, an oral glucose tolerance test (OGTT) was performed. Insulin resistance (IR) was assessed using HOMA-IR index. Insulin sensitivity (IS) was assessed according to the Matsuda formula. Genomic DNA from obese and control children was genotyped for genetic variants of PPARG, ADIPOQ, ADIPOR1, FTO, TCF7L2, and KCNJ11 using a real-time PCR strategy. The unpaired Student's t-test and Kruskal-Wallis one-way test were used to compare quantitative data in two and more groups. To assess the extent to which the various genetic variants were associated with pathology, ORs (odds ratios) and 95% CI (confidence interval) were estimated. RESULTS: In T2D children, HOMA-IR value (7.5+/-3.1) was significantly (P<0.001) higher than that in IGT (4.21+/ 2.25) and NGT (4.1+/-2.4) subjects. The Matsuda IS index was significantly increased in normoglycemic patients compared to IGT individuals (2.8+/-1.75 vs. 2.33+/-1.2, P<0.05). The Pro12Ala polymorphism of PPARG was significantly associated with obesity (OR=1.74, 95% CI=1.19-2.55, P=0.004) and T2D in obesity (OR=2.01, 95% CI=1.24-3.26, P=0.004). CONCLUSION: IR is a major risk factor that mediates progression from NGT to clinical T2D in Russian obese children. This progression may be genetically influenced by the Pro12Ala variant of PPARG. PMID- 25127331 TI - Heteroaggregation of titanium dioxide nanoparticles with model natural colloids under environmentally relevant conditions. AB - The heteroaggregation of engineered nanoparticles (ENPs) with natural colloids (NCs), which are ubiquitous in natural surface waters, is a crucial process affecting the environmental transport and fate of ENPs. Attachment efficiencies for heteroaggregation, alpha hetero, are required as input parameters in environmental fate models to predict ENP concentrations and contribute to ENP risk assessment. Here, we present a novel method for determining alpha hetero values by using a combination of laser diffraction measurements and aggregation modeling based on the Smoluchowski equation. Titanium dioxide nanoparticles (TiO2 NPs, 15 nm) were used to demonstrate this new approach together with larger silicon dioxide particles (SiO2, 0.5 MUm) representing NCs. Heteroaggregation experiments were performed at different environmentally relevant solution conditions. At pH 5 the TiO2 NPs and the SiO2 particles are of opposite charge, resulting in alpha hetero values close to 1. At pH 8, where all particles are negatively charged, alpha hetero was strongly affected by the solution conditions, with alpha hetero ranging from <0.001 at low ionic strength to 1 at conditions with high NaCl or CaCl2 concentrations. The presence of humic acid stabilized the system against heteroaggregation. PMID- 25127332 TI - Characteristics of acute heart failure hospitalizations in a general medical ward in Southwestern Uganda. PMID- 25127333 TI - Morphologic characteristics of eroded coronary plaques: a combined angiographic, optical coherence tomography, and intravascular ultrasound study. PMID- 25127334 TI - Seven french radial artery access for PCI: a prospective single-center experience. PMID- 25127335 TI - Precordial chest pain in patients with chronic Chagas disease. AB - Precordial chest pain affects about 15% to 33% of patients with chronic Chagas disease. In the absence of megaesophagus, it should be ascribed to chronic Chagas heart disease. Precordial chest pain is atypical because it can usually neither be associated to physical exercise nor be alleviated by nitroglycerin. However, in certain circumstances, precordial chest pain can masquerade as acute coronary syndrome. Although obstructive coronary artery disease can occasionally be found, microvascular angina seems to be the mechanism behind such phenomenon. Precordial chest pain not always has a benign clinical course; sometimes, it can herald a dismal prognosis. On the basis of cases previously reported, it seems that nitrates, betablockers and/or calcium channel blockers can be of value in the treatment of this condition. PMID- 25127336 TI - Acute eosinophilic myocarditis. PMID- 25127337 TI - Early changes of myocardial deformation properties in patients with dystrophia myotonica type 1: a three-dimensional Speckle Tracking echocardiographic study. PMID- 25127338 TI - Real-time photoacoustic imaging system for burn diagnosis. AB - We have developed a real-time (8 to 30 fps) photoacoustic (PA) imaging system with a linear-array transducer for burn depth assessment. In this system, PA signals originating from blood in the noninjured tissue layer located under the injured tissue layer are detected and imaged. A compact home-made high-repetition rate (500 Hz) 532-nm fiber laser was incorporated as a light source. We used an alternating arrangement for the fibers and sensor elements in the probe, which improved the signal-to-noise ratio, reducing the required laser energy power for PA excitation. This arrangement also enabled a hand-held light-weight probe design. A phantom study showed that thin light absorbers embedded in the tissue mimicking scattering medium at depths >3 mm can be imaged with high contrast. The maximum error for depth measurement was 140 MUm. Diagnostic experiments were performed for rat burn models, including superficial dermal burn, deep dermal burn, and deep burn models. Injury depths (zones of stasis) indicated by PA imaging were compared with those estimated by histological analysis, showing discrepancies 200 MUm. The system was also used to monitor the healing process of a deep dermal burn. The results demonstrate the potential usefulness of the present system for clinical burn diagnosis. PMID- 25127339 TI - Copper-catalyzed domino reactions for the synthesis of cyclic compounds. AB - Copper-catalyzed domino reactions are one of the most useful strategies for the construction of various cyclic compounds. In this Synopsis, we mainly focus on the latest advances in copper-catalyzed cross-coupling or addition-initiated domino reactions in the synthesis of cyclic compounds, including double alkenylation of N- or S-nucleophiles, alkenylation or alkynlation followed by cyclization of amides or amines, addition and cyclization of heteroallenes affording heterocycles, and coupling and cyclization of 1,3-dicarbonyl compounds toward heterocycles. PMID- 25127340 TI - Colloids with continuously tunable surface charge. AB - In this paper, we present a robust way to tune the surface potential of polystyrene colloids without changing the pH, ionic strength, etc. The colloids are composed of a cross-linked polystyrene core and a cross-linked vinylbenzyl chloride layer. Besides the chlorine groups, the particle surface contains sulfate/sulfonate groups (arising from the polymerization initiators) that provide a negative surface potential. Performing a Menschutkin reaction on the surface chlorine groups with tertiary amines allows us to introduce quaternary, positively charged amines. The overall charge on the particles is then determined by the ratio between the sulfate/sulfonate moieties and the quaternary amines. Using this process, we were able to invert the charge in a continuous manner without losing colloidal stability upon passing the isoelectric point. The straightforward reaction mechanism together with the fact that the reaction could be quenched rapidly resulted in a colloidal system in which the zeta potential can be tuned between -80 and 45 mV. As proof of principle, the positively charged particles were used in heterocoagulation experiments with nanometer- and micrometer-sized negatively charged silica particles to create geometrically well defined colloidal (nano) clusters. PMID- 25127341 TI - Social self-perception among pediatric brain tumor survivors compared with peers. AB - OBJECTIVE: To assess self-perceptions of social behavior among children treated for a brain tumor and comparison children. To investigate group differences in the accuracy of children's self-perceptions as measured by discrepancies between self and peer reports of social behavior and to understand if these phenomena differ by gender. METHOD: Self and peer reports of social behavior were obtained in the classrooms of 116 children who were treated for an intracranial tumor. Social behaviors were assessed using the Revised Class Play, which generates indices for 5 behavioral subscales: Leadership-popularity, Prosocial, Aggressive disruptive, Sensitive-isolated, and Victimization. A child matched for gender, race, and age was selected from each survivor's classroom to serve as a comparison. Abbreviated IQ scores were obtained in participants' homes. RESULTS: Relative to comparison children, those who had undergone treatment for a brain tumor overestimated their level of Leadership-popularity and underestimated levels of Sensitive-isolated behaviors and Victimization by peers. Female survivors were more likely than male survivors to underestimate Sensitive isolated behaviors and Victimization. CONCLUSION: Following treatment for a brain tumor, children (particularly girls) may be more likely than healthy children to underestimate peer relationship difficulties. These discrepancies should be considered when obtaining self-report from survivors and developing interventions to improve social functioning. PMID- 25127342 TI - "More than meets the eye": when the neonatal course may impact several years out. AB - CASE: Nadia is a 7-year-old girl who you have followed since her discharge from the Neonatal Intensive Care Unit (NICU). Her parents are here today for an urgent visit with behavioral concerns, such as inattention, hyperactivity, and aggression.Nadia is a former 40-weeker born through vacuum-assisted vaginal delivery at 9 pounds 7 ounces. Her delivery was complicated with shoulder dystocia, which resulted in resuscitation. Her Apgar scores were 1, 3, and 4 at 1, 5, and 10 minutes, respectively. After intubation and stabilization on mechanical ventilation, Nadia was transferred to the NICU. Her neonatal course included systemic hypothermia using "cool cap" for hypoxic-ischemic encephalopathy (HIE) for a duration of 72 hours. She was extubated on day of life 3. She had an occupational therapy consultation for poor suck/feeding, and it quickly improved. She was discharged on day of life 14. On discharge, Nadia was referred to early intervention (EI) and the NICU follow-up clinic. Nadia was followed by EI until 12 months of age and in the NICU follow-up clinic until 18 months of age, as there were no concerns meeting her developmental milestones or her neuromotor development.At this urgent visit, Nadia's parents report that she attended a family child care from 1.5 to 3 years of age, Head Start from 3 to 5 years of age and the local public school from 5 years to present. Since starting child care, Nadia's teachers have reported that she requires a lot of redirection and refocusing, fidgets a lot in class, and can be aggressive toward her peers when unprovoked. Since her parents had not seen these behaviors at home, they thought it was a phase that she would grow out of. However, as they began to work with her to complete school assignments, they noticed that it was very difficult for Nadia to sit still and focus on work. They also struggled in the mornings to get her ready and off to school.The parents bring in Conners scales completed by themselves and her lead teacher, and with these and our clinical observations, we diagnose her with attention-deficit/hyperactivity disorder (ADHD), combined type. We discuss risk factors and ADHD management with her parents. During our discussion, Nadia's father, who has done some reading on ADHD, remembers reading an article about HIE and NICU stay being risk factors for ADHD. He wonders if this affects the choice of management of her ADHD symptoms. How would you address his query? PMID- 25127344 TI - [Discussion welcome]. PMID- 25127343 TI - Perfluorochemicals and human semen quality: the LIFE study. AB - BACKGROUND: The relation between persistent environmental chemicals and semen quality is evolving, although limited data exist for men recruited from general populations. OBJECTIVES: We examined the relation between perfluorinated chemicals (PFCs) and semen quality among 501 male partners of couples planning pregnancy. METHODS: Using population-based sampling strategies, we recruited 501 couples discontinuing contraception from two U.S. geographic regions from 2005 through 2009. Baseline interviews and anthropometric assessments were conducted, followed by blood collection for the quantification of seven serum PFCs (perfluorosulfonates, perfluorocarboxylates, and perfluorosulfonamides) using tandem mass spectrometry. Men collected a baseline semen sample and another approximately 1 month later. Semen samples were shipped with freezer packs, and analyses were performed on the day after collection. We used linear regression to estimate the difference in each semen parameter associated with a one unit increase in the natural log-transformed PFC concentration after adjusting for confounders and modeling repeated semen samples. Sensitivity analyses included optimal Box-Cox transformation of semen quality end points. RESULTS: Six PFCs [2 (N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), perfluorooctane sulfonamide (PFOSA), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA)] were associated with 17 semen quality end points before Box-Cox transformation. PFOSA was associated with smaller sperm head area and perimeter, a lower percentage of DNA stainability, and a higher percentage of bicephalic and immature sperm. PFDeA, PFNA, PFOA, and PFOS were associated with a lower percentage of sperm with coiled tails. CONCLUSIONS: Select PFCs were associated with certain semen end points, with the most significant associations observed for PFOSA but with results in varying directions. PMID- 25127345 TI - [Substance abuse and pregnancy from an obstetric point of view]. AB - INTRODUCTION: In Germany we find about 2 000 newborns per year with a mother misusing drugs. It is to be feared that there is a substantial amount of underreported substance abuse in pregnant women. To care for these pregnancies from an obstetric point of view as well as from an addiction treatment point of view is a challenge for all health-care professionals, due to multiple drugs being used and the special psychosocial and health issues these mothers and babies -present. METHOD: A selective search was undertaken in Pubmed, retrieving reviews and original articles from 2001-2013, with consideration of statements, recommendations and guidelines from national and international associations and committees on the topic. This review is intended to assist gynaecologists, obstetricians and paediatricians during the complex peripartum care for the drug abusing pregnant patient. RESULTS: When offering obstetric care for these pregnancies, several issues have to be taken into account: the special psychological situation of the pregnant drug user, with frequent occurrence of psychiatric comorbidities like depression and anxiety disorders, as well as gynaecological complications like premature labour, intrauterine growth restriction and maternal infectious diseases. The pharmacological complexity of the substances abused and the possible side-effects on the foetus have to be explained to the mother. Maintenance medication for foetomaternal risk reduction and maternal stabilisation remains the state-of-the-art treatment. Furthermore, it is important to explain the neonatal abstinence syndrome to the mother as well as the result of breast-feeding in the presence of smoking and/or infectious diseases. DISCUSSION: Professionalism and empathy are needed from gynaecologists in order to achieve risk reduction for mother and child in substance-using pregnancies. However, in spite of close cooperation of all health-care professionals and avoidance of stigma, it will be difficult to offer good obstetric care to the high-risk patients with poly-drug abuse. PMID- 25127346 TI - [Preconceptional use of folic acid in the region of the Kantonsspital Munsterlingen/Thurgau: has it changed over the past 10 years?]. AB - BACKGROUND: Numerous studies have shown that the preconceptional use of folic acid prevents neural tube defects. We created a study to find out whether the preconceptional use of folic acid has improved in the past 10 years, in the area of Munsterlingen, Switzerland. MATERIAL AND METHODS: We interviewed 2 groups of patients who delivered at our Institution, namely between 2000 and 2002 (period A) involving 287 women and from 2009 to 2010 (period B) involving 305 pregnant women. We asked them whether they used folic acid by means of a standardised questionnaire. RESULTS: In period B significantly more women have taken folic acid preconceptionally (period A: 27.5% vs. period B: 40.7%; p=0.001). A significant increase in folic acid intake was seen in the German speaking group from period A to B (30.3% vs. 52.7%; p=0.0005), while this was not the case in the non-German speaking group (21.4% in both periods). More multiparae women were taking folic acid compared to nulliparae. A significant increase from period A to B was noted only in the German speaking group. Unexpectedly, in nulliparae non German speaking women, folic acid supplementation decreased from 14% to 6.1%. DISCUSSION: We have found a significant increase in preconceptional folic acid supplementation from 2001 to 2010. The percentage of women taking folic acid is disappointingly low in all groups, particularly in nulliparae women of non-German ethnicity. PMID- 25127347 TI - [Infant mortality in Germany (2008-2012)--lower in the former German Democratic Republic?]. AB - BACKGROUND: German infant mortality is ranked near the median of European countries. In Germany infant mortality is significantly higher in the German Federal Republic compared with the former German Democratic Republic. This is often used as reason for a call for structural requirements and minimum caseload for the care for very low birth weight infants. METHOD: Neonatal and infant mortality were calculated for the 16 German federal states with data from the German statistical federal office for the years 2008-2012. RESULTS: Considerable variations were found for the neonatal (1.34-3.610/00, total Germany 2.310/00) and the infant (2.38-5.200/00, 3.470/00) mortality. The rate of stillborn infants was 3.560/00. A lower neonatal mortality in the former German Democratic Republic (1.620/00 vs. 2.440/00, p<0.0001, Chi-squared test) could not be confirmed for preterm infants with birth weight less than 1 500 g. In the former German Democratic Republic stillbirth was significantly more frequent in preterm infants with birth weight 500-999 g (p<0.0001). Combined stillbirth and neonatal mortality showed no difference between the German Federal Republic and former German Democratic Republic (5.450/00 and 5.290/00, respectively, n.s.; infants less than 500 g birth weight were excluded). The average number of preterm infants per perinatal centre and federal state had no influence on state specific neonatal mortality. CONCLUSION: If stillborn infants were accounted for no difference was found between the German Federal Republic and the former German Democratic Republic regarding mortality. Comparing infant mortality of different countries has to account for stillborn infants. Considerable variation of neonatal mortality is persisting throughout Germany despite structural requirements and introduction of a minimum caseload since 2005. A lower infant mortality in the former German Democratic Republic and implications drawn from are not supported by the presented nationwide data from the German statistical federal office. PMID- 25127348 TI - [Infant mortality in Germany (2008-2012) - lower in the East?]. PMID- 25127349 TI - [Quality results in perinatal centers]. PMID- 25127350 TI - [Prevention of preterm birth by Shirodkar cerclage--clinical results of a retrospective analysis]. AB - In spite of the continuous progress in prenatal care, 1 out of 10 babies is born too early--tendency rising worldwide. As a consequence of the heterogeneous aetiology of preterm birth, there is still no single and efficient interventional therapy. Cerclage is one option for pregnancies with cervical insufficiency, whereas the clinical benefit is discussed controversially. We analyzed in a retrospective study with 120 patients the effect of a cerclage intervention regarding pregnancy prolongation. Patients with cervical incompetence and Shirodkar cerclage were compared to those undergoing conservative treatment. As expected, gestational age at delivery was significantly lower after emergency cerclage (31 weeks) compared to prophylactic (36 weeks) and therapeutic cerclage (35 weeks). Prolongation differs significantly between the prophylactic (18 weeks), therapeutic (14 weeks) and emergency cerclage (10 weeks) groups. Conservative management achieved 8 weeks prolongation. Of note, particularly emergency cerclage in cases with advanced cervical incompetence resulted in a substantially higher pregnancy prolongation (10 weeks) compared to no intervention (one week). The efficiency of cerclage operations has to be assessed in a differentiated manner based on the clinical situation and indication. The clinical benefit depends strongly on proper patient selection. PMID- 25127351 TI - Successful treatment of 1-34 parathyroid hormone (PTH) after failure of bisphosphonate therapy in a complex case of pregnancy associated osteoporosis and multiple fractures. AB - INTRODUCTION: Pregnancy associated osteoporosis (PAO) was first reported almost half a century ago. The most common symptom is acute lower back pain due to vertebral fractures in the last trimester or immediately after birth. PATIENT: We present a case involving a female patient born in 1971 (gravida II, para I) with a history of PAO. In April 2000 at the age of 28 years, she delivered a son and breastfed him for 4 months. A first magnetic resonance tomography (MRT) screening in June 2000 showed osteoporotic fractures at lumbar vertebra 1-4. Therefore, the patient received oral alendronate therapy. In May 2001, a second MRT exhibited burst fracture of thoracic 8, end-plate fracture of thoracic 11, 12, lumbar 2-5 and compression fracture of lumbar 1. The oral therapy was switched to ibandronate (3 mg) intravenously every 3 months. An X-ray in December 2002 showed 3 new additional end-plate fractures at thoracic 4, 6 and 7. Ibandronate was discontinued in September 2004 and the patient received daily subcutaneous (s. c.) injections of 1-34 PTH in September 2005. RESULTS: After starting 1-34 PTH treatment for 18 months, a further increase in bone mineral density (BMD) was achieved without any further fracture. CONCLUSION: We presented for the first time a case of severe PAO with 11 spine fractures. We observed an unsatisfactory effect of oral and i. v. bisphosphonates in combination with adequate calcium and vitamin D supplementation. The treatment with 1-34 PTH showed an increase in BMD with no further fractures. PMID- 25127352 TI - Maternite Prize of the European Association of Perinatal Medicine. Laudatio for Christian P. Speer, MD, FRCPE Professor of Pediatrics. PMID- 25127354 TI - The browning of white adipose tissue: some burning issues. AB - Igniting thermogenesis within white adipose tissue (i.e., promoting expression and activity of the uncoupling protein UCP1) has attracted much interest. Numerous "browning agents" have now been described (gene ablations, transgenes, food components, drugs, environments, etc.). The implied action of browning agents is that they increase UCP1 through this heat production, leading to slimming. Here, we particularly point to the possibility that cause and effect may on occasion be the reverse: browning agents may disrupt, for example, the fur, leading to increased heat loss, increased thermogenic demand to counteract this heat loss, and thus, through sympathetic nervous system activation, to enhanced UCP1 expression in white (and brown) adipose tissues. PMID- 25127353 TI - Fatty acid flippase activity of UCP2 is essential for its proton transport in mitochondria. AB - Modulation of cellular energy expenditure is fundamental to normal and pathological cell growth and differentiation. Mitochondria stores energy as a proton gradient across their inner membrane. Uncoupling proteins (UCPs) can dissipate the gradient to produce heat or regulate metabolite fluxes. UCP mediated proton currents require fatty acids (FAs) and are blocked by nucleotides, but the molecular basis of these processes is unknown. We find, by nuclear magnetic resonance and functional mutagenesis, that UCP2 can bind FAs laterally through its peripheral site, and this intramembrane molecular recognition is essential for UCP2-catalyzed FA flipping across the membrane, which in turn is essential for proton translocation. The antagonist GDP binds inside the UCP2 cavity and perturbs its conformation, which can displace FA from the peripheral site as a mean of inhibiting proton currents. Our data provide a biophysical perspective of the intricate interplay of UCPs, FA, and nucleotides in determining proton fluxes in mitochondria. PMID- 25127355 TI - Aggregation behavior of engineered nanoparticles and their impact on activated sludge in wastewater treatment. AB - The ever-increasing daily use of engineered nanoparticles will lead to heightened levels of these materials in the environment. These nanomaterials will eventually go into the wastewater treatment plant (WWTP), therefore, resulting into a pressing need for information on their aggregation behavior and kinetics in the wastewater aqueous matrix. In this work, we dispersed two different metal oxide nanoparticles (ZnO and TiO2) into the influent of two different WWTPs. Through the time-resolved dynamic light scattering analysis and transmission electron microscopy, the metal oxide nanoparticles (NPs) were quite stably existed in the wastewater matrix with aggregates of diameter 300-400 nm after 4.5h or more suspension. We confirmed that the dissolved organic matters (DOMs) attributed to the stability of nanoparticles. No propensity of NPs to aggregate were observed in the presence of both monovalent and divalent electrolytes even at high concentrations up to 0.15 M in NaCl or 0.025 M in CaCl2, indicating that the destabilization of nanoparticles in the complicated wastewater matrix was not achieved by the compression of electrical double layer, therefore, their aggregation kinetics cannot be simply predicted by the classic Derjaguin-Landau Verwey-Overbeek theory of colloidal stability. However, obvious aggregation of nanoparticles in the Al2(SO4)3 solution system was observed with the likely mechanism of bridging of the metal oxide nanoparticles and aggregates due to the formation of hydrous alumina (Al(OH)3.H2O) in the Al2(SO4)3 solution. In the wastewater matrix, we used the noninvasive measurement technology to detect the O2 flux of activated sludge before and after treatment with 1, 10 and 100 mg L( 1) NPs. The results confirmed that both ZnO and TiO2 NPs showed an adverse impact on the O2 uptake of activated sludge when the exposure time extended to 4.5 h. PMID- 25127356 TI - The role of P450 metabolism in the estrogenic activity of bifenthrin in fish. AB - Bifenthrin, a pyrethroid pesticide, is estrogenic in vivo in fishes. However, bifenthrin is documented to be anti-estrogenic in vitro, in the ER-CALUX (estrogen receptor) cell line. We investigated whether metabolite formation is the reason for this incongruity. We exposed Menidia beryllina (inland silversides) to 10ng/l bifenthrin, 10ng/l 4-hydroxy bifenthrin, and 10ng/l bifenthrin with 25MUg/l piperonyl butoxide (PBO) - a P450 inhibitor. Metabolite exposed juveniles had significantly higher estrogen-mediated protein levels (choriogenin) than bifenthrin/PBO-exposed, while bifenthrin alone was intermediate (not significantly different from either). This suggests that metabolites are the main contributors to bifenthrin's in vivo estrogenicity. PMID- 25127357 TI - Effect of bisphenol A on P-glycoprotein-mediated efflux and ultrastructure of the sea urchin embryo. AB - Usage of bisphenol A (BPA) in production of polycarbonate plastics has resulted in global distribution of BPA in the environment. These high concentrations cause numerous negative effects to the aquatic biota, among which the most known is the induction of endocrine disruption. The focus of this research was to determine the effects of two experimentally determined concentrations of BPA (100nM and 4MUM) on cellular detoxification mechanisms during the embryonic development (2 cell, pluteus) of the rocky sea urchin (Paracentrotus lividus), primarily the potential involvement of multidrug efflux transport in the BPA intercellular efflux. The results of transport assay, measurements of the intracellular BPA and gene expression surveys, for the first time indicate the importance of P glycoprotein (P-gp/ABCB1) in defense against BPA. Cytotoxic effects of BPA, validated by the immunohistochemistry (IHC) and the transmission electron microscopy (TEM), induced the aberrant karyokinesis, and consequently, the impairment of embryo development through the first cell division and retardation. PMID- 25127358 TI - The prevalence of abnormal genital findings, vulvovaginitis, enuresis and encopresis in children who present with allegations of sexual abuse. AB - OBJECTIVE: To assess the prevalence of vulvovaginitis, enuresis and encopresis in children who were referred for allegations of sexual abuse. SUBJECTS: A retrospective chart review of 1280 children presenting for non-acute examination after allegations of sexual abuse during a 15-year time span. Interview documentation, physical examination documentation, urinalysis, urine and vaginal cultures were reviewed. RESULTS: Of the 1280 children, 73.3% were female and 26.7% male. The ages of the children ranged from 6 months to 18 years (median age was 6 years). Interviews revealed that fondling contact was the most common allegation, followed by oral, vaginal, and anal penetration. Interviews also disclosed lower urinary tract symptoms, UTI, constipation, encopresis and enuresis. Physical examination revealed no abnormal genital findings in 44.7% of cases. Examinations of the vagina noted: erythema (18.1%); hymenal notching (posterior 16.8%, anterior 4.4%); vuvlovaginitis (14.0%); laceration or transection (0.6%); and bruising (0.4%). Examination of the anus noted: anal fissure/tear (14.9%); loss of anal tone (10.6%); reflex anal dilatation (9.2%); venous congestion (3.8%); and proctitis (0.9%). Vulvovaginitis was noted in 14% (131/936) and encopresis in 2.3% (21/936). Enuresis according to age was reported in 13% of 5-9 year olds, 14.7% of 10-16 year olds and 18.2% of 17-18 year olds suspected of being abused. CONCLUSION: Prevalence of vulvovaginitis and enuresis were increased, and encopresis was decreased in children with allegations of sexual abuse when compared to the general pediatric population. Physicians should continue to be aware of the possibility of the presence of these conditions in children who have been sexually abused, and offer appropriate treatment. PMID- 25127359 TI - Inhibition of glycogen synthase kinase-3beta attenuates glucocorticoid-induced suppression of myogenic differentiation in vitro. AB - Glucocorticoids are the only therapy that has been demonstrated to alter the progress of Duchenne muscular dystrophy (DMD), the most common muscular dystrophy in children. However, glucocorticoids disturb skeletal muscle metabolism and hamper myogenesis and muscle regeneration. The mechanisms involved in the glucocorticoid-mediated suppression of myogenic differentiation are not fully understood. Glycogen synthase kinase-3beta (GSK-3beta) is considered to play a central role as a negative regulator in myogenic differentiation. Here, we showed that glucocorticoid treatment during the first 48 h in differentiation medium decreased the level of phosphorylated Ser9-GSK-3beta, an inactive form of GSK 3beta, suggesting that glucocorticoids affect GSK-3beta activity. We then investigated whether GSK-3beta inhibition could regulate glucocorticoid-mediated suppression of myogenic differentiation in vitro. Two methods were employed to inhibit GSK-3beta: pharmacological inhibition with LiCl and GSK-3beta gene knockdown. We found that both methods resulted in enhanced myotube formation and increased levels of muscle regulatory factors and muscle-specific protein expression. Importantly, GSK-3beta inhibition attenuated glucocorticoid-induced suppression of myogenic differentiation. Collectively, these data suggest the involvement of GSK-3beta in the glucocorticoid-mediated impairment of myogenic differentiation. Therefore, the inhibition of GSK-3beta may be a strategy for preventing glucocorticoid-induced muscle degeneration. PMID- 25127361 TI - A fluorescence color-encoded lipid-supported polymeric particle. AB - Several fluorescent or luminescent organisms with biological, chemical, and ecological diversity have been proposed as substitutes for use in new imaging and diagnostic technologies. Inspired by these trends, we designed a synthetic fluorescent light-encoding particulate to serve as a novel and prospective cancer diagnostic imaging platform. The fluorescence-emitting particulate was used practically for both in vitro and in vivo selective cancer diagnostic imaging. PMID- 25127360 TI - Genetic characterization of Toxoplasma gondii isolates and toxoplasmosis seroprevalence in stray cats of Izmir, Turkey. AB - Currently, some Toxoplasma gondii genotypes are being associated with serious clinical presentations. A recent report showing the Africa 1 genotype in two local congenital toxoplasmosis cases acquired in Turkey formed the basis of this study because atypical Africa 1 genotype is most frequently detected in animals and patients from sub-Saharan Africa. Since stray cats are considered as the linkage between wild life and urban life in T. gondii transmission, the present study aimed to isolate and characterize T. gondii strains circulating in stray cats of Izmir (Western Turkey). A secondary objective was to determine toxoplasmosis seroprevalence in this cat population. Tissues obtained from 100 deceased stray cats were bioassayed and isolated strains were genotyped using 15 microsatellite markers. In addition, toxoplasmosis seroprevalence was analyzed in 1121 cat sera collected from several large veterinary clinics in Izmir. Among the 22 isolates, 19 were Type II (86.3%), two were Type III (9%) and one was Africa 1 genotype (4.5%). The overall seropositivity rates in cats were 42-48% and 33.4 34.4% according to IFA and ELISA, respectively. Seroprevalence in deceased cats was significantly higher than in healthy cats (P = 0.0033). Finding both the major clonal Type II lineage together with the Type III lineage also found in Middle East, and an atypical genotype, Africa 1 appears consistent with the specific geographic location of Turkey between three continents and raises the possibility of transportation of these strains between continents through trade routes or long distance migratory birds. In addition, the first large study of toxoplasma seroprevalence in a stray cat population was also reported. The relatively high seropositivity rates and the variety of T. gondii genotypes confirm the local stray cat population as a risk factor for human toxoplasmosis in Izmir. PMID- 25127362 TI - Mineralization and drug release of hydroxyapatite/poly(l-lactic acid) nanocomposite scaffolds prepared by Pickering emulsion templating. AB - Biodegradable and bioactive nanocomposite (NC) biomaterials with controlled microstructures and able to deliver special drugs have gained increasing attention in bone tissue engineering. In this study, the hydroxyapatite (HAp)/poly(l-lactic acid) (PLLA) NC scaffolds were facilely prepared using solvent evaporation from templating Pickering emulsions stabilized with PLLA modified HAp (g-HAp) nanoparticles. Then, in vitro mineralization experiments were performed in a simulated body fluid (SBF) to evaluate the bioactivity of the NC scaffolds. Moreover, in vitro drug release of the NC scaffolds using anti inflammatory drug (ibuprofen, IBU) as the model drug was also investigated. The results showed that the NC scaffolds possessed interconnected pore structures, which could be modulated by varying the g-HAp nanoparticle concentration. The NC scaffolds exhibited excellent bioactivity, since they induced the formation of calcium-sufficient, carbonated apatite nanoparticles on the scaffolds after mineralization in SBF for 3 days. The IBU loaded in the NC scaffolds showed a sustained release profile, and the release kinetic followed the Higuchi model with diffusion process. Thus, solvent evaporation based on Pickering emulsion droplets is a simple and effective method to prepare biodegradable and bioactive porous NC scaffolds for bone repair and replacement applications. PMID- 25127364 TI - Delivery of antisense peptide nucleic acids to cells by conjugation with small arginine-rich cell-penetrating peptide (R/W)9. AB - Peptide nucleic acids (PNAs) are very attractive antisense and antigene agents, but these molecules are not passively taken into cells. Here, using a functional cell assay and fluorescent-based methods, we investigated cell uptake and antisense activity of a tridecamer PNA that targets the HIV-1 polypurine tract sequence delivered using the arginine-rich (R/W)9 peptide (RRWWRRWRR). At micromolar concentrations, without use of any transfection agents, almost 80% inhibition of the target gene expression was obtained with the conjugate in the presence of the endosomolytic agent chloroquine. We show that chloroquine not only induced escape from endosomes but also enhanced the cellular uptake of the conjugate. Mechanistic studies revealed that (R/W)9-PNA conjugates were internalized via pinocytosis. Replacement of arginines with lysines reduced the uptake of the conjugate by six-fold, resulting in the abolition of intracellular target inhibition. Our results show that the arginines play a crucial role in the conjugate uptake and antisense activity. To determine whether specificity of the interactions of arginines with cell surface proteoglycans result in the internalization, we used flow cytometry to examine uptake of arginine- and lysine rich conjugates in wild-type CHO-K1 and proteoglycan-deficient A745 cells. The uptake of both conjugates was decreased by four fold in CHO-745 cells; therefore proteoglycans promote internalization of cationic peptides, irrespective of the chemical nature of their positive charges. Our results show that arginine-rich cell-penetrating peptides, especially (R/W)9, are a promising tool for PNA internalization. PMID- 25127363 TI - Application of a combination of a knowledge-based algorithm and 2-stage screening to hypothesis-free genomic data on irinotecan-treated patients for identification of a candidate single nucleotide polymorphism related to an adverse effect. AB - Interindividual variation in a drug response among patients is known to cause serious problems in medicine. Genomic information has been proposed as the basis for "personalized" health care. The genome-wide association study (GWAS) is a powerful technique for examining single nucleotide polymorphisms (SNPs) and their relationship with drug response variation; however, when using only GWAS, it often happens that no useful SNPs are identified due to multiple testing problems. Therefore, in a previous study, we proposed a combined method consisting of a knowledge-based algorithm, 2 stages of screening, and a permutation test for identifying SNPs. In the present study, we applied this method to a pharmacogenomics study where 109,365 SNPs were genotyped using Illumina Human-1 BeadChip in 168 cancer patients treated with irinotecan chemotherapy. We identified the SNP rs9351963 in potassium voltage-gated channel subfamily KQT member 5 (KCNQ5) as a candidate factor related to incidence of irinotecan-induced diarrhea. The p value for rs9351963 was 3.31*10-5 in Fisher's exact test and 0.0289 in the permutation test (when multiple testing problems were corrected). Additionally, rs9351963 was clearly superior to the clinical parameters and the model involving rs9351963 showed sensitivity of 77.8% and specificity of 57.6% in the evaluation by means of logistic regression. Recent studies showed that KCNQ4 and KCNQ5 genes encode members of the M channel expressed in gastrointestinal smooth muscle and suggested that these genes are associated with irritable bowel syndrome and similar peristalsis diseases. These results suggest that rs9351963 in KCNQ5 is a possible predictive factor of incidence of diarrhea in cancer patients treated with irinotecan chemotherapy and for selecting chemotherapy regimens, such as irinotecan alone or a combination of irinotecan with a KCNQ5 opener. Nonetheless, clinical importance of rs9351963 should be further elucidated. PMID- 25127365 TI - Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice. AB - UbiA prenyltransferase domain containing 1 (UBIAD1) is a novel vitamin K2 biosynthetic enzyme screened and identified from the human genome database. UBIAD1 has recently been shown to catalyse the biosynthesis of Coenzyme Q10 (CoQ10) in zebrafish and human cells. To investigate the function of UBIAD1 in vivo, we attempted to generate mice lacking Ubiad1, a homolog of human UBIAD1, by gene targeting. Ubiad1-deficient (Ubiad1(-/-)) mouse embryos failed to survive beyond embryonic day 7.5, exhibiting small-sized body and gastrulation arrest. Ubiad1(-/-) embryonic stem (ES) cells failed to synthesize vitamin K2 but were able to synthesize CoQ9, similar to wild-type ES cells. Ubiad1(+/-) mice developed normally, exhibiting normal growth and fertility. Vitamin K2 tissue levels and synthesis activity were approximately half of those in the wild-type, whereas CoQ9 tissue levels and synthesis activity were similar to those in the wild-type. Similarly, UBIAD1 expression and vitamin K2 synthesis activity of mouse embryonic fibroblasts prepared from Ubiad1(+/-) E15.5 embryos were approximately half of those in the wild-type, whereas CoQ9 levels and synthesis activity were similar to those in the wild-type. Ubiad1(-/-) mouse embryos failed to be rescued, but their embryonic lifespans were extended to term by oral administration of MK-4 or CoQ10 to pregnant Ubiad1(+/-) mice. These results suggest that UBIAD1 is responsible for vitamin K2 synthesis but may not be responsible for CoQ9 synthesis in mice. We propose that UBIAD1 plays a pivotal role in embryonic development by synthesizing vitamin K2, but may have additional functions beyond the biosynthesis of vitamin K2. PMID- 25127369 TI - The effects of musical practice on structural plasticity: the dynamics of grey matter changes. AB - Intensive training and the acquisition of expertise are known to bring about structural changes in the brain. Musical training is a particularly interesting model. Previous studies have reported structural brain modifications in the auditory, motor and visuospatial areas of musicians compared with nonmusicians. The main goal of the present study was to go one step further, by exploring the dynamic of those structural brain changes related to musical experience. To this end, we conducted a regression study on 44 nonmusicians and amateur musicians with 0-26years of musical practice of a variety instruments. We sought first to highlight brain areas that increased with the duration of practice and secondly distinguish (thanks to an ANOVA analysis) brain areas that undergo grey matter changes after only limited years of musical practice from those that require longer practice before they exhibit changes. Results revealed that musical training results a greater grey matter volumes in different brain areas for musicians. Changes appear gradually in the left hippocampus and right middle and superior frontal regions, but later also include the right insula and supplementary motor area and left superior temporal, and posterior cingulate areas. Given that all participants had the same age and that we controlled for age and education level, these results cannot be ascribed to normal brain maturation. Instead, they support the notion that musical training could induce dynamic structural changes. PMID- 25127366 TI - Dengue virus 2 American-Asian genotype identified during the 2006/2007 outbreak in Piaui, Brazil reveals a Caribbean route of introduction and dissemination of dengue virus in Brazil. AB - Dengue virus (DENV) is the most widespread arthropod-borne virus, and the number and severity of outbreaks has increased worldwide in recent decades. Dengue is caused by DENV-1, DENV- 2, DENV-3 and DENV-4 which are genetically distant. The species has been subdivided into genotypes based on phylogenetic studies. DENV-2, which was isolated from dengue fever patients during an outbreak in Piaui, Brazil in 2006/2007 was analyzed by sequencing the envelope (E) gene. The results indicated a high similarity among the isolated viruses, as well as to other DENV 2 from Brazil, Central America and South America. A phylogenetic and phylogeographic analysis based on DENV-2E gene sequences revealed that these viruses are grouped together with viruses of the American-Asian genotype in two distinct lineages. Our results demonstrate the co-circulation of two American Asian genotype lineages in northeast Brazil. Moreover, we reveal that DENV-2 lineage 2 was detected in Piaui before it disseminated to other Brazilian states and South American countries, indicating the existence of a new dissemination route that has not been previously described. PMID- 25127371 TI - Epilepsy, comorbid conditions in Canadian children: analysis of cross-sectional data from cycle 3 of the National Longitudinal Study of Children and Youth. AB - PURPOSE: The purpose of this study was to analyze national survey data to provide estimates of prevalence of epilepsy and associated developmental disabilities and comorbid conditions. METHODS: We analyzed data from Cycle 3 of Canada's National Longitudinal Survey of Children and Youth. The NLSCY captured, socio-demographic information, as well as age, sex, education, ethnicity, household income, chronic health related conditions from birth to 15 years old. The main survey question intended to identify "epilepsy", "cerebral palsy", "intellectual disability", "learning disability", and "emotional and nervous difficulties" in the population of children surveyed. Prevalence was based on the national cross-sectional sample and used 1000 bootstrap weights to account for survey design factors. RESULTS: Cycle 3 of the NLSCY had the largest number of patients with diagnosed epilepsy. Prevalence figures (n/1000) for epilepsy and cerebral palsy (EPI_CP), epilepsy and intellectual disability (EPI_ID), epilepsy and learning disability (EPI_LD), and epilepsy and emotional nervous difficulties (EPI_EMO_NERV) were 1.1, 1.17, 2.58 and 1.34 respectively. Amongst children with epilepsy, 43.17% reported the presence of one or more of the above comorbid conditions. CONCLUSION: These results provide an initial prevalence estimate of comorbid conditions with epilepsy in Canadian children. In a high proportion of children with epilepsy, the PMK had reported at least one comorbid disorder. These findings carry implications for health care utilization and long-term outcomes. We discuss methodological aspects related to the ascertainment of epilepsy in both surveys, and to the validity and implications of our findings. PMID- 25127372 TI - The impact of web-based HOT (Healthy Outcomes for Teens) Project on risk for type 2 diabetes: a randomized controlled trial. AB - BACKGROUND: The HOT (Healthy Outcome for Teens) Project is an innovative online educational intervention for middle school children for prevention of diabetes and obesity by balancing food intake with physical activity. The objective was to improve knowledge, outcome expectations, self-efficacy, and self-reported food intake and skills and to compare a passive online learning (POL) control group with an active online learning (AOL) treatment group by implementing a social cognitive theory (SCT)-grounded online intervention. SUBJECTS AND METHODS: In total, 214 participants were recruited from three middle schools. Full data were secured for 181 students. Six valid, reliable questionnaires were administered online, pre/post, to both the AOL and POL groups to assess knowledge gain, self reported intake, and meal planning skills, as well as change in SCT constructs. RESULTS: Subjects in the AOL group improved significantly for all five categories of planning a meal questionnaire (P=0.001) and also for outcome expectations for exercise (P=0.001). At postintervention, no significant differences were found for composite scores of exercise self-efficacy, weight efficacy lifestyle, and rapid eating assessment plan questionnaires between AOL versus POL (by Mann Whitney test). CONCLUSIONS: We conclude that teens participating in the AOL version of the HOT Project intervention acquired skills for planning a meal and improved outcome expectations for exercise. PMID- 25127370 TI - Clinical correlates of graph theory findings in temporal lobe epilepsy. AB - PURPOSE: Temporal lobe epilepsy (TLE) is considered a brain network disorder, additionally representing the most common form of pharmaco-resistant epilepsy in adults. There is increasing evidence that seizures in TLE arise from abnormal epileptogenic networks, which extend beyond the clinico-radiologically determined epileptogenic zone and may contribute to the failure rate of 30-50% following epilepsy surgery. Graph theory allows for a network-based representation of TLE brain networks using several neuroimaging and electrophysiologic modalities, and has potential to provide clinicians with clinically useful biomarkers for diagnostic and prognostic purposes. METHODS: We performed a review of the current state of graph theory findings in TLE as they pertain to localization of the epileptogenic zone, prediction of pre- and post-surgical seizure frequency and cognitive performance, and monitoring cognitive decline in TLE. RESULTS: Although different neuroimaging and electrophysiologic modalities have yielded occasionally conflicting results, several potential biomarkers have been characterized for identifying the epileptogenic zone, pre-/post-surgical seizure prediction, and assessing cognitive performance. For localization, graph theory measures of centrality have shown the most potential, including betweenness centrality, outdegree, and graph index complexity, whereas for prediction of seizure frequency, measures of synchronizability have shown the most potential. The utility of clustering coefficient and characteristic path length for assessing cognitive performance in TLE is also discussed. CONCLUSIONS: Future studies integrating data from multiple modalities and testing predictive models are needed to clarify findings and develop graph theory for its clinical utility. PMID- 25127373 TI - Comparison of platelet serotonin transporter activity in subjects with severe sleep bruxism and control. AB - PURPOSE: The aim of this study was to evaluate the correlation between sleep bruxism (SB) frequency and serotonin transporter (SERT)-driven serotonin (5-HT) uptake in platelets. METHODS: Subjects were dental trainee residents and faculty members of Okayama University Hospital who were aware of having severe or no SB. SB frequency was assessed for 3-consecutive nights by a self-contained electromyographic detector/analyzer, which indicated individual SB levels as one of four grades (score 0, 1, 2 and 3). Subjects were classified as normal control (NC) when SB scores indicated only 0 or 1 during the 3 nights, or as severe SB for scores 2 or 3. Those subjects whose scores fluctuated from 0 to 3 during the 3 nights were omitted from further analysis. Fasting peripheral venous blood samples were collected in the morning following the final SB assessment. Amounts of SERTs proteins collected from peripheral platelets were quantified using ELISA, and SERTs transport activity was assessed by uptake assay using [3H]-5-HT. RESULTS: Thirteen severe SB subjects and 7 NC subjects were eligible. Gender distribution, mean age, 5-HT concentration and total amounts of SERT protein in platelets showed no significant differences between NC and severe SB (p=0.85: Chi squared test; p=0.64, 0.26, 0.46: t-test). However, [3H]-5-HT uptake by platelets was significantly greater in NC compared to severe SB subjects (12.79+/-1.97, 8.27+/-1.91 fmol/10(5) platelets/min, p<0.001, t-test). CONCLUSION: The results of this pilot study suggest a possible correlation between peripheral platelet serotonin transporter uptake ability and SB severity. PMID- 25127374 TI - Nuclear mobility and activity of FOXA1 with androgen receptor are regulated by SUMOylation. AB - Forkhead box (FOX) protein A1 has been dubbed a pioneer transcription factor because it binds target sites in DNA, thereby displacing nucleosomes to loosen chromatin and facilitating steroid receptor DNA binding nearby. FOXA1 is an important regulator of prostate development, collaborating with androgen receptor (AR). Post-translational modifications regulating FOXA1 are thus far poorly understood. SUMOylation, post-translational modification of proteins by small ubiquitin-like modifier (SUMO) proteins, has emerged as an important regulatory mechanism in transcriptional regulation. In this work, we show by SUMOylation assays in COS-1 cells that the FOXA1 is modified at least in two of its three lysines embedded in SUMOylation consensus, K6 and K389, in proximity to its transactivation domains and K267 proximal to its DNA-binding domain. We also provide evidence for SUMO-2/3 modification of endogenous FOXA1 in LNCaP prostate cancer cells. Based on fluorescence recovery after photobleaching assays with mCherry-fused FOXA1 and EGFP-fused AR in HEK293 cells, the presence of FOXA1 retards the nuclear mobility of agonist-bound AR. Interestingly, mutation of the FOXA1 SUMOylation sites slows down the mobility of the pioneer factor, further retarding the nuclear mobility of the AR. Chromatin immunoprecipitation and gene expression assays suggest that the mutation enhances FOXA1's chromatin occupancy as well as its activity on AR-regulated prostate-specific antigen (PSA) locus in LNCaP cells. Moreover, the mutation altered the ability of FOXA1 to influence proliferation of LNCaP cells. Taken together, these results strongly suggest that the SUMOylation can regulate the transcriptional activity of FOXA1 with the AR. PMID- 25127376 TI - Effect of different head and neck positions on behaviour, heart rate variability and cortisol levels in lunged Royal Dutch Sport horses. AB - Different head-and-neck positions (HNPs) are discussed in relation to potential welfare issues. To evaluate the effect on welfare, seven Royal Dutch Sport horses were studied in five predetermined HNPs: (1) unrestrained (HNP1); (2) neck raised, bridge of nose around the vertical (HNP2); (3) neck lowered and considerably flexed, bridge of nose pointing towards the chest (HNP4); (4) neck raised and extended, bridge of nose in front of the vertical (HNP5), and (5) neck lowered and flexed, bridge of nose pointing towards the carpus (HNP7). A standardised exercise test (SET) of 34 min consisted of trot, canter and walk. Behaviour was recorded with a pre-defined ethogram and R-R intervals measured using telemetry. Cortisol concentrations were taken at the start, 5 and 30 min after the SET. Behaviour around the SET was scored separately. Conflict behaviours increased significantly during HNP2 when compared with HNP1, HNP4 and HNP7 during the SET, and there was significant negative anticipation before HNP2 and HNP7. The heart rate variability (HRV) frequency domain for HNP2 showed a significantly increased low frequency peak (LFpeak) compared with other HNPs, and there was a decrease in very low frequency (VLF%) compared with HNP1. HNP4 showed a significant increase in LF% and decrease in VLF% compared with HNP1. Saliva cortisol concentrations were significantly increased in HNP2 at 5 and 30 min after exercise. Increased conflict behaviour was mostly observed in HNP2, but there was a raised HRV suggesting a sympathetic shift in HNP2 and HNP4, and increased cortisol concentrations during HNP2 indicated a stress response. PMID- 25127377 TI - Finite element analysis of three commonly used external fixation devices for treating Type III pilon fractures. AB - Pilon fractures are commonly caused by high energy trauma and can result in long term immobilization of patients. The use of an external fixator i.e. the (1) Delta, (2) Mitkovic or (3) Unilateral frame for treating type III pilon fractures is generally recommended by many experts owing to the stability provided by these constructs. This allows this type of fracture to heal quickly whilst permitting early mobilization. However, the stability of one fixator over the other has not been previously demonstrated. This study was conducted to determine the biomechanical stability of these external fixators in type III pilon fractures using finite element modelling. Three-dimensional models of the tibia, fibula, talus, calcaneus, navicular, cuboid, three cuneiforms and five metatarsal bones were reconstructed from previously obtained CT datasets. Bones were assigned with isotropic material properties, while the cartilage was assigned as hyperelastic springs with Mooney-Rivlin properties. Axial loads of 350 N and 70 N were applied at the tibia to simulate the stance and the swing phase of a gait cycle. To prevent rigid body motion, the calcaneus and metatarsals were fixed distally in all degrees of freedom. The results indicate that the model with the Delta frame produced the lowest relative micromovement (0.03 mm) compared to the Mitkovic (0.05 mm) and Unilateral (0.42 mm) fixators during the stance phase. The highest stress concentrations were found at the pin of the Unilateral external fixator (509.2 MPa) compared to the Mitkovic (286.0 MPa) and the Delta (266.7 MPa) frames. In conclusion, the Delta external fixator was found to be the most stable external fixator for treating type III pilon fractures. PMID- 25127375 TI - Lipocalin 2 is a regulator of macrophage polarization and NF-kappaB/STAT3 pathway activation. AB - Lipocalin 2 (Lcn2) has been previously characterized as an adipokine/cytokine and implicated in obesity and inflammation. Herein, we investigated the role and potential mechanism of Lcn2 in the regulation of macrophage polarization in obesity-associated inflammation. We observed that Lcn2-/- mice displayed an up regulation of expression of M1 macrophage marker Cd11c but a down-regulation of M2 marker arginase 1 in adipose tissue and liver of mice upon a high-fat diet feeding. Lcn2-deficient bone marrow-derived macrophages (BMDMs) were more sensitive to lipopolysaccharide (LPS) stimulation, leading to a more profound up regulation of expression of pro-inflammatory markers than wild-type (WT) BMDMs. Accordingly, LPS stimulation elicited an increase in the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), c-Jun, and STAT3 signaling pathways as well as an up-regualtion of expression of NF-kappaB and STAT3 target genes such as IL-1beta, IL-6, iNOS, and MCP-1 in Lcn2-/- BMDMs compared with WT controls. Pre-treatment of recombinant Lcn2 attenuated LPS stimulated degradation of IkappaBalpha and STAT3 phosphorylation as well as LPS induced gene expression of IL-6 and iNOS in Lcn2-/- BMDMs. Moreover, the NFkappaB inhibitor markedly blocked LPS-stimulated STAT3 phosphorylation in Lcn2-/- BMDMs. These results together with the time course of Lcn2 secretion, NFkappaB and STAT3 phosphorylation in response to LPS stimulation, suggest that Lcn2 plays a role as an anti-inflammatory regulator in macrophage activation via modulating a feed forward activation of NFkappaB-STAT3 loop. PMID- 25127379 TI - Impacts of groundwater discharge at Myora Springs (North Stradbroke Island, Australia) on the phenolic metabolism of eelgrass, Zostera muelleri, and grazing by the juvenile rabbitfish, Siganus fuscescens. AB - Myora Springs is one of many groundwater discharge sites on North Stradbroke Island (Queensland, Australia). Here spring waters emerge from wetland forests to join Moreton Bay, mixing with seawater over seagrass meadows dominated by eelgrass, Zostera muelleri. We sought to determine how low pH/high CO2 conditions near the spring affect these plants and their interactions with the black rabbitfish (Siganus fuscescens), a co-occurring grazer. In paired-choice feeding trials S. fuscescens preferentially consumed Z. muelleri shoots collected nearest to Myora Springs. Proximity to the spring did not significantly alter the carbon and nitrogen contents of seagrass tissues but did result in the extraordinary loss of soluble phenolics, including Folin-reactive phenolics, condensed tannins, and phenolic acids by >=87%. Conversely, seagrass lignin contents were, in this and related experiments, unaffected or increased, suggesting a shift in secondary metabolism away from the production of soluble, but not insoluble, (poly)phenolics. We suggest that groundwater discharge sites such as Myora Springs, and other sites characterized by low pH, are likely to be popular feeding grounds for seagrass grazers seeking to reduce their exposure to soluble phenolics. PMID- 25127380 TI - Orthodontic treatment of an adult patient with severe crowding and unilateral missing premolars. PMID- 25127378 TI - Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG uptake is highest in hypoxic tumor regions. AB - PURPOSE: Intratumoral metabolic heterogeneity may increase the likelihood of treatment failure due to the presence of a subset of resistant tumor cells. Using a head and neck squamous cell carcinoma (HNSCC) xenograft model and a real-time fluorescence imaging approach, we tested the hypothesis that tumors are metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose uptake within the tumor. EXPERIMENTAL DESIGN: Cal33 cells were grown as xenograft tumors (n = 16) in nude mice after identification of this cell line's metabolic response to hypoxia. Tumor uptake of fluorescent markers identifying hypoxia, glucose import, or vascularity was imaged simultaneously using fluorescent molecular tomography. The variability of intratumoral 2-deoxyglucose (IR800-2-DG) concentration was used to assess tumor metabolic heterogeneity, which was further investigated using immunohistochemistry for expression of key metabolic enzymes. HNSCC tumors in patients were assessed for intratumoral variability of (18)F fluorodeoxyglucose ((18)F-FDG) uptake in clinical PET scans. RESULTS: IR800-2-DG uptake in hypoxic regions of Cal33 tumors was 2.04 times higher compared to the whole tumor (p = 0.0001). IR800-2-DG uptake in tumors containing hypoxic regions was more heterogeneous as compared to tumors lacking a hypoxic signal. Immunohistochemistry staining for HIF-1alpha, carbonic anhydrase 9, and ATP synthase subunit 5beta confirmed xenograft metabolic heterogeneity. We detected heterogeneous (18)F-FDG uptake within patient HNSCC tumors, and the degree of heterogeneity varied amongst tumors. CONCLUSION: Hypoxia is associated with increased intratumoral metabolic heterogeneity. (18)F-FDG PET scans may be used to stratify patients according to the metabolic heterogeneity within their tumors, which could be an indicator of prognosis. PMID- 25127381 TI - Progressive slicing of second deciduous molars in a young patient with second premolar agnesis. PMID- 25127382 TI - Mini-implant-supported temporary pontics. PMID- 25127383 TI - A rapid maxillary expander with differential opening. PMID- 25127384 TI - Resin reinforcement: an alternative approach for direct bonding of molar tubes. PMID- 25127385 TI - Scoring of ceramic bracket bases for easier debonding. PMID- 25127386 TI - Removal of aqueous Hg(II) and Cr(VI) using phytic acid doped polyaniline/cellulose acetate composite membrane. AB - Conductive composite membrane-phytic acid (PA) doped polyaniline (PANI)/cellulose acetate (CA) (PANI-PA/CA) was prepared in a simple and environmental-friendly method, in which aniline was blended with CA/PA solution and polymerized before the phase conversion. The resultant composite membranes were characterized by SEM, EDX, FTIR-ATR, BET and electrical resistance measurements. When used as adsorbent for Hg(II) and Cr(VI) ions, the prepared composite membrane exhibits excellent adsorption capability. The adsorption of Hg(II) and Cr(VI) follows a pseudo-second-order kinetic model and best fits the Langmuir isotherm model, with the maximum adsorption capacity reaching 280.11 and 94.34 mg g(-1), respectively. The heavy metal loaded composite membrane can be regenerated and reused after treatment with acid or alkali solution, making it a promising and practical adsorbent for Hg(II) and Cr(VI) removal. Tests with river water were also carried out, indicating good performance and application. PMID- 25127387 TI - Reaction of carbon tetrachloride with methane in a non-equilibrium plasma at atmospheric pressure, and characterisation of the polymer thus formed. AB - In this paper we focus on the development of a methodology for treatment of carbon tetrachloride utilising a non-equilibrium plasma operating at atmospheric pressure, which is not singularly aimed at destroying carbon tetrachloride but rather at converting it to a non-hazardous, potentially valuable commodity. This method encompasses the reaction of carbon tetrachloride and methane, with argon as a carrier gas, in a quartz dielectric barrier discharge reactor. The reaction is performed under non-oxidative conditions. Possible pathways for formation of major products based on experimental results and supported by quantum chemical calculations are outlined in the paper. We elucidate important parameters such as carbon tetrachloride conversion, product distribution, mass balance and characterise the chlorinated polymer formed in the process. PMID- 25127388 TI - Specific and ultrasensitive ciprofloxacin detection by responsive photonic crystal sensor. AB - A new approach for specific and ultrasensitive measurement of ciprofloxacin has been developed by integrating ternary complexes into responsive photonic crystal (RPC). Tryptophan was first immobilized within the polyacrylamide hydrogel substrates of RPC. The determination of ciprofloxacin was via the existence of zinc(II) ions that function as a 'bridge' to form specific tryptophan-zinc(II) ciprofloxacin complexes step by step, which resulted in a stepwise red-shift of the diffraction wavelength. A maximum wavelength shift from 798 to 870 nm for ciprofloxacin was observed when the RPC film was immersed in 10(-4)M ciprofloxacin. A linear relationship has been obtained between the Deltalambda of diffraction peak and logarithm of ciprofloxacin concentration at pH 5.0 in the range of 10(-10) to 10(-4)M. And the least detectable concentration in present work is about 5 * 10(-11)M. The results demonstrated that the as-designed ternary complexes-based RPC sensor exhibited high sensitivity, satisfactory specificity and excellent recoverability for sensing of ciprofloxacin in aqueous media and were validated by detecting ciprofloxacin in the eye-drop sample. PMID- 25127389 TI - Graphene oxide as an effective catalyst for wet air oxidation of phenol. AB - The graphene oxide (GO) and chemically reduced graphene oxides, used as catalysts in absence of any metals, were investigated in the catalytic wet air oxidation (CWAO) of phenol in a batch reactor. The characterization of the materials was measured with scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman, fourier transform infrared spectroscopy (FT-IR) and X ray photoelectron spectroscopy (XPS). The carbon materials exhibited good phenol and total organic compounds (TOC) removals in the CWAO of phenol. The GO had the highest catalytic activity, total phenol removal was achieved after 40 min, and ca. 84% TOC removal was obtained after 120 min at reaction temperature of 155 degrees C, total pressure of 2.5 MPa and catalyst loading of 0.2 gL(-1). PMID- 25127390 TI - What predicts the first peak of the knee adduction moment? AB - BACKGROUND: The first peak of the knee adduction moment curve during walking has been shown to be a good clinical surrogate measure of medial tibiofemoral joint loading and osteoarthritis. Defining the relative contributions of the variables that dictate the knee adduction moment, such as center of mass, center of pressure, vertical ground reaction force, and knee adduction angle (i.e. lower limb alignment), has not been formally investigated within the same cohort of individuals. Therefore, the goal of this study was to determine which of these variables is the biggest determinant of the first peak of knee adduction moment curve. METHODS: Instrumented gait analysis was collected for 30 individuals. Variables significantly correlated with the peak knee adduction moment were input into a stepwise multi-variable linear regression model. RESULTS: The knee adduction angle predicted 58% of the variance in the first peak knee adduction moment and the vertical ground reaction force magnitude predicted the second most variance (20%). CONCLUSIONS: The most effective way to modify the peak knee adduction moment may be to change the knee adduction angle (e.g. off loader brace), followed by changing the vertical magnitude of the ground reaction force (e.g. cane use). CLINICAL RELEVANCE: Defining the major determinants of the knee adduction moment may help guide clinicians in choosing conservative interventions to reduce it in conditions such as medial tibiofemoral osteoarthritis. PMID- 25127391 TI - Generation and behavior characterization of CaMKIIbeta knockout mice. AB - The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the brain, where it makes important contributions to synaptic organization and homeostasis, including playing an essential role in synaptic plasticity and memory. Four genes encode isoforms of CaMKII (alpha, beta, delta, gamma), with CaMKIIalpha and CaMKIIbeta highly expressed in the brain. Decades of molecular and cellular research, as well as the use of a large number of CaMKIIalpha mutant mouse lines, have provided insight into the pivotal roles of CaMKIIalpha in brain plasticity and cognition. However, less is known about the CaMKIIbeta isoform. We report the development and extensive behavioral and phenotypic characterization of a CaMKIIbeta knockout (KO) mouse. The CaMKIIbeta KO mouse was found to be smaller at weaning, with an altered body mass composition. The CaMKIIbeta KO mouse showed ataxia, impaired forelimb grip strength, and deficits in the rotorod, balance beam and running wheel tasks. Interestingly, the CaMKIIbeta KO mouse exhibited reduced anxiety in the elevated plus maze and open field tests. The CaMKIIbeta KO mouse also showed cognitive impairment in the novel object recognition task. Our results provide a comprehensive behavioral characterization of mice deficient in the beta isoform of CaMKII. The neurologic phenotypes and the construction of the genotype suggest the utility of this KO mouse strain for future studies of CaMKIIbeta in brain structure, function and development. PMID- 25127392 TI - A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia. AB - Aurora kinase overexpression has been observed in patients with hematologic malignancies. MK-0457, a pan-aurora kinase inhibitor that also inhibits the ABL T315I mutant, was evaluated to treat patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) with the T315I mutation. Adults with Ph+ chronic phase (CP)-, accelerated phase (AP)- or blast phase (BP)-CML, or ALL and documented BCR-ABL T315I mutation were treated with a 5-day continuous infusion of MK-0457 administered every 14 days at 40 mg/m(2)/h, 32 mg/m(2)/h or 24 mg/m(2)/h. Fifty-two patients (CP, n=15; AP, n=14; BP, n=11; Ph+ ALL, n=12) were treated. Overall, 8% of patients achieved major cytogenetic response; 6% achieved unconfirmed complete or partial response; 39% had no response. Two patients (CP CML) achieved complete hematologic response. No patients with advanced CML or Ph+ ALL achieved major hematologic response. The most common adverse event (AE) was neutropenia (50%). The most common grade 3/4 AEs were neutropenia (46%) and febrile neutropenia (35%). MK 0457 demonstrated minimal efficacy and only at higher, intolerable doses; lower doses were tolerated and no unexpected toxicities were observed. These data will assist in the development of future aurora kinase inhibitors and in the selection of appropriate target patient populations. PMID- 25127393 TI - Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis. AB - The aim of this study was to understand the clinical features and treatment outcome of Chinese patients with multiple myeloma (MM). This retrospective study enrolled 940 newly diagnosed inpatients (median age, 59 years; immunoglobulin (Ig)D isotype, 6.5%) with complete follow-up data at three centers. In all, 85.8% of patients were of Durie-Salmon stage III and 48.3% were of International Staging System (ISS) stage III at diagnosis. Also, 9.6% of patients had extramedullary plasmacytoma. Compared with IgG, IgD-type patients were diagnosed at a younger age, and more patients were of ISS stage III, with hypercalcemia, elevated levels of lactate dehydrogenase, hyperuricemia, renal dysfunction and 1q21 amplification (P=0.03). The overall survival (OS) benefit was more prominent in IgG than in IgD when patients received bortezomib; however, they showed no significant difference when they received older therapies such as melphalan combined with prednisone or vincristine combined with adriamycin and dexamethasone. Fluorescence in situ hybridization (FISH) results showed that 17.6% had 17p13 deletion. Conventional cytogenetics revealed that 13.3% were hypodiploid and those cases had the worst survival, but hyperdiploid cases (9.3%) did not show any survival benefit compared with those with a normal karyotype (77.4%). Median OS and progression-free survival for all patients were 54 and 26 months, respectively. Significant factors for survival by multivariate analysis were gender, ISS stage, number of FISH abnormalities and extramedullary disease. MM in mainland China presents with different features, with patients being of younger age and having higher risk and more survival benefit in IgG patients receiving bortezomib. PMID- 25127394 TI - Correlation of prostatic urethral angle with the severity of urinary symptom and peak flow rate in men with small prostate volume. AB - PURPOSE: To evaluate the effects of prostatic anatomical factors on male lower urinary tract symptoms (LUTS) and the peak flow rate (Qmax) in patients with small prostate volume (PV). MATERIALS AND METHODS: Records were obtained from a prospectively maintained database of first-visit men with LUTS. Patients whose total PV (TPV) was greater than 30 mL were excluded; 444 patients were enrolled in the study. The TPV, transitional zone volume (TZV), transitional zone index (TZI), intravesical prostatic protrusion (IPP), and prostatic urethral angle (PUA) were measured by transrectal ultrasonography. LUTS were evaluated using the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS) questionnaires. Uroflowmetric measurements were also made. RESULTS: PUA (r = 0.269, P<0.001), TZV (r = 0.160, P<0.001), and TZI (r = 0.109, P = 0.022) significantly correlated with the IPSS. Qmax (r = -0.334, P<0.001) and OABSS (r = 0.211, P<0.001) correlated only with PUA. In a multivariate regression analysis, PUA and age were independently associated with IPSS, OABSS, and Qmax. For IPSS of 20 or greater, the area under the ROC curve (AUC) of PUA was 0.667 and the cut-off value was 43.7 degrees . When Qmax was 10 mL/s or less, the AUC of PUA was 0.664 and the cut-off value was 43.5 degrees . CONCLUSIONS: PUA has a significant association with symptom severity and Qmax among prostatic anatomical factors analyzed in men with LUTS and small PV. PUA should be considered as an important clinical factor in male LUTS management. Furthermore, the impact of PUA on response to medical treatment and disease progression needs to be investigated. PMID- 25127395 TI - A simple efficient synthesis and biological evaluation of 3-O-ethylascorbic acid. AB - A single-step synthesis of 3-O-ethyl-l-ascorbic acid was performed without the induction of protecting groups. Sodium l-ascorbate reacted with ethyl bromide in DMSO to give 3-O-ethylascorbic acid in a yield of 51.0%. 3-O-Ethylascorbic acid enhanced dibutyryl cyclic AMP-induced neurite outgrowth in PC12 cells. PMID- 25127396 TI - Socioeconomic dynamics of gender disparity in childhood immunization in India, 1992-2006. AB - BACKGROUND: Recent evidence indicated that gender disparity in child health is minimal and narrowed over time in India. However, considering the geographical and socio-cultural diversity in India, the gender gap may persist across disaggregated socioeconomic context which may be masked by average level. This study examines the dynamics of gender disparity in childhood immunization across regions, residence, wealth, caste and religion in India during 1992-2006. METHOD: We used multi-waves of the cross-sectional data of National Family Health Survey conducted in India between 1992-93 and 2005-06. Gender disparity ratio was used to measure the gender gap in childhood immunization across the selected socioeconomic characteristics. Multinomial regression analysis was used to examine the gender gap after accounting for other covariates. RESULT: Results indicate that, at aggregate level, gender disparity in full immunization is minimal and has stagnated during the study period. However, gender disparity- disfavouring female children--becomes apparent across the regions, poor households, and religion--particularly among Muslims. Adjusted gender disparity ratio indicates that, full immunization is lower among female than male children of the western region, poor household and among Muslims. Between 1992-93 and 2005 06, the disparity in full immunization had narrowed in the northern region whereas it had, astonishingly, increased in some of the western and southern states of the country. CONCLUSION: Our findings emphasize the need to integrate gender issues in the ongoing immunization programme in India, with particular attention to urban areas, developed states, and to the Muslim community. PMID- 25127398 TI - Climate change sensitivity index for Pacific salmon habitat in southeast Alaska. AB - Global climate change may become one of the most pressing challenges to Pacific Salmon conservation and management for southeast Alaska in the 21st Century. Predicted hydrologic change associated with climate change will likely challenge the ability of specific stocks to adapt to new flow regimes and resulting shifts in spawning and rearing habitats. Current research suggests egg-to-fry survival may be one of the most important freshwater limiting factors in Pacific Salmon's northern range due to more frequent flooding events predicted to scour eggs from mobile spawning substrates. A watershed-scale hydroclimatic sensitivity index was developed to map this hypothesis with an historical stream gauge station dataset and monthly multiple regression-based discharge models. The relative change from present to future watershed conditions predicted for the spawning and incubation period (September to March) was quantified using an ensemble global climate model average (ECHAM5, HadCM3, and CGCM3.1) and three global greenhouse gas emission scenarios (B1, A1B, and A2) projected to the year 2080. The models showed the region's diverse physiography and climatology resulted in a relatively predictable pattern of change: northern mainland and steeper, snow-fed mountainous watersheds exhibited the greatest increases in discharge, an earlier spring melt, and a transition into rain-fed hydrologic patterns. Predicted streamflow increases for all watersheds ranged from approximately 1-fold to 3 fold for the spawning and incubation period, with increased peak flows in the spring and fall. The hydroclimatic sensitivity index was then combined with an index of currently mapped salmon habitat and species diversity to develop a research and conservation priority matrix, highlighting potentially vulnerable to resilient high-value watersheds. The resulting matrix and observed trends are put forth as a framework to prioritize long-term monitoring plans, mitigation experiments, and finer-scale climate impact and adaptation studies. PMID- 25127397 TI - Association between domestic violence and HIV serostatus among married and formerly married women in Kenya. AB - The prevalence of both domestic violence (DV) and HIV among Kenyan women is known to be high, but the relationship between them is unknown. Nationally representative cross-sectional data from married and formerly married (MFM) women responding to the Kenya Demographic and Health Survey 2008/2009 were analyzed adjusting for complex survey design. Multivariable logistic regressions were used to assess the covariate-adjusted associations between HIV serostatus and any reported DV as well as four constituent DV measures: physical, emotional, sexual, and aggravated bodily harm, adjusting for covariates entered into each model using a forward stepwise selection process. Covariates of a priori interest included those representing marriage history, risky sexual behavior, substance use, perceived HIV risk, and sociodemographic characteristics. The prevalence of HIV among MFM women was 10.7% (any DV: 13.1%, no DV: 8.6%); overall prevalence of DV was 43.4%. Among all DV measures, only physical DV was associated with HIV (11.9%; adjusted odds ratio: 2.01, p <.05). Efforts by the government and women's groups to monitor and improve policies to reduce DV, such as the Sexual Offences Act of 2006, are urgently needed to curb HIV, as are policies that seek to provide DV counseling and treatment to MFM women. PMID- 25127399 TI - Benefit of shading by nurse plant does not change along a stress gradient in a coastal dune. AB - The proximity of adult neighbors often increases the performance of woody seedlings under harsh environmental conditions but this nurse plant effect becomes less intense when abiotic stress is alleviated, as predicted by the stress gradient hypothesis (SGH). Although some studies have tested how the net nurse effect is changed by stress, few studies have tested how the mechanism that drives the facilitative effect of nurse responds to changes in stress. We conducted field experiments in a subtropical coastal dune to test if shading drives the known nurse effect of adults of the tree Guapira opposita on seedling performance of another tree species, Ternstroemia brasiliensis. We transplanted T. brasiliensis seedlings to three neighbor environments: under a G. opposita crown, under artificial shade and without neighbor as a control. Furthermore, assuming that proximity to the seashore correlates with stress intensity, we tested if the potential shade-driven facilitation became less intense as stress decreased. Regardless of the proximity to the seashore, after a year, the survival of T. brasiliensis seedlings was twice as high when the seedlings were under G. opposita or under artificial shade compared to the control, indicating that the nurse effect is driven by shade and that this facilitation mechanism is constant along the stress gradient. However, G. opposita and artificial shade had a negative effect on seedlings growth. Overall, our results showed that the facilitation mechanism behind the nurse effect did not wane as the stress was reduced. Furthermore, in spite of the potential costs in terms of biomass production, our study highlights the potential of nurse plants and artificial shade as techniques to improve the survival of transplanted seedlings used in the restoration of degraded shrubland coastal dunes. PMID- 25127400 TI - Use of cloneable peptide-MBP fusion protein as a mimetic coating antigen in the standardized immunoassay for mycotoxin ochratoxin A. AB - The quality of mycotoxin conjugates is essential to the development of reliability of immunoassays for mycotoxins. However, conventional mycotoxin conjugates are usually synthesized by chemical methods, which are harmful to the environment and yield unwanted cross-reactions. In this study, using ochratoxin A (OTA) as a model system, a selected OTA mimotope (phage-displayed peptide) that specifically binds to anti-OTA antibody was expressed as soluble and monovalent fusions to maltose binding protein (MBP). These prepared fusion proteins can serve as a mimetic coating antigen in both a quantitative chemiluminescent enzyme linked immunoassay (CLEIA) and a qualitative dot immunoassay for OTA. One of the prepared mimetic coating antigen (L12-206-MBP)-based CLEIAs exhibited a half inhibition concentration (IC50) of 0.82 ng/mL and a working range of 0.30-2.17 ng/mL, which resemble those of the conventional OTA-OVA conjugate-based immunoassay. The dot immunoassay developed with both the OTA-OVA conjugate and the mimetics showed identical visual cutoff values of 5 ng/mL. The mimetic coating antigen proposed here is an OTA-free product and can be prepared reproducibly as a homogeneous product and facilitates standardization of immunoassays for the mycotoxin OTA. PMID- 25127401 TI - Chelation gradients for investigation of metal ion binding at silica surfaces. AB - Centimeter-long surface gradients in bi- and tridentate chelating agents have been formed via controlled rate infusion, and the coordination of Cu(2+) and Zn(2+) to these surfaces has been examined as a function of distance by X-ray photoelectron spectroscopy (XPS). 3-(Trimethoxysilylpropyl)ethylenediamine and 3 (trimethoxysilylpropyl)diethylenetriamine were used as precursor silanes to form the chelation gradients. When the gradients were exposed to a metal ion solution, a series of coordination complexes formed along the length of the substrate. For both chelating agents at the three different concentrations studied, the amine content gradually increased from top to bottom as expected for a surface chemical gradient. While the Cu 2p peak area had nearly the same profile as nitrogen, the Zn 2p peak area did not and exhibited a plateau along much of the gradient. The normalized nitrogen-to-metal peak area ratio (N/M) was found to be highly dependent on the type of ligand, its surface concentration, and the type of metal ion. For Cu(2+), the N/M ratio ranged from 8 to 11 on the diamine gradient and was ~4 on the triamine gradient, while for Zn(2+), the N/M ratio was 4-8 on diamine and 5-7 on triamine gradients. The extent of protonation of amine groups was higher for the diamine gradients, which could lead to an increased N/M ratio. Both 1:1 and 1:2 ligand/metal complexes along with dinuclear complexes are proposed to form, with their relative amounts dependent on the ligand, ligand density, and metal ion. Collectively, the methods and results described herein represent a new approach to study metal ion binding and coordination on surfaces, which is especially important to the extraction, preconcentration, and separation of metal ions. PMID- 25127403 TI - Be it ever so humble... PMID- 25127402 TI - Transcriptional landscape of glomerular parietal epithelial cells. AB - Very little is known about the function of glomerular parietal epithelial cells (PECs). In this study, we performed genome-wide expression analysis on PEC enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the transcriptional state of PECs under normal conditions. We identified hundreds of differentially expressed genes that mapped to distinct biologic modules including development, tight junction, ion transport, and metabolic processes. Since developmental programs were highly enriched in PECs, we characterized several of their candidate members at the protein level. Collectively, our findings confirm that PECs are multifaceted cells and help define their diverse functional repertoire. PMID- 25127404 TI - Remodeling a broken system through hospital-payer partnerships. AB - One way to fix our broken system is to strengthen hospital-payer partnerships, which will help shift caregiver focus from volume to value. PMID- 25127406 TI - Dose and timing of prenatal tobacco exposure: threats to early child development. PMID- 25127407 TI - Dynamic analysis of a needle insertion for soft materials: Arbitrary Lagrangian Eulerian-based three-dimensional finite element analysis. AB - BACKGROUND: Our goal was to develop a three-dimensional finite element model that enables dynamic analysis of needle insertion for soft materials. To demonstrate large deformation and fracture, we used the arbitrary Lagrangian-Eulerian (ALE) method for fluid analysis. We performed ALE-based finite element analysis for 3% agar gel and three types of copper needle with bevel tips. METHODS: To evaluate simulation results, we compared the needle deflection and insertion force with corresponding experimental results acquired with a uniaxial manipulator. We studied the shear stress distribution of agar gel on various time scales. RESULTS: For 30 degrees , 45 degrees , and 60 degrees , differences in deflections of each needle between both sets of results were 2.424, 2.981, and 3.737mm, respectively. For the insertion force, there was no significant difference for mismatching area error (p<0.05) between simulation and experimental results. CONCLUSIONS: Our results have the potential to be a stepping stone to develop pre-operative surgical planning to estimate an optimal needle insertion path for MR image-guided microwave coagulation therapy and for analyzing large deformation and fracture in biological tissues. PMID- 25127405 TI - Effect of nicotine patches in pregnancy on infant and maternal outcomes at 2 years: follow-up from the randomised, double-blind, placebo-controlled SNAP trial. AB - BACKGROUND: The SNAP (Smoking and Nicotine in Pregnancy) trial compared nicotine replacement therapy (NRT) patches with placebo in pregnant smokers; although NRT doubled cessation rates in the first 4 weeks, by delivery no differences in maternal smoking or birth outcomes were noted. As a result, NRT used in standard doses during pregnancy is considered ineffective for smoking cessation. Subsequent effects of NRT on the children of treated mothers are unknown because no trials have investigated the effect of gestational NRT use beyond birth. To assess whether NRT use in pregnancy might cause harm to infants, we aimed to compare effects of NRT and placebo on infant development 2 years after delivery. METHODS: 1050 pregnant smokers aged 16-45 years, at 12-24 weeks' gestation, and smoking at least five cigarettes per day were recruited from seven hospitals in England between May 1, 2007, and Feb 26, 2010, and followed up until their infants were 2 years old. Participants were randomly assigned (1:1) to receive up to 8-weeks treatment with NRT (15 mg/16 h transdermal patches) or identically packaged and visually matched placebo patches (all patches manufactured by and purchased at market rate from United Pharmaceuticals, Amman, Jordan), issued as two 4-week supplies (521 for NRT group, 529 for placebo group) [Corrected]. Randomisation was stratified by site with participants, health-care professionals, and research staff masked to treatment allocation. The primary results for participants and infants at delivery were published in 2012; we present results from the trial cohort 2 years after birth. After delivery, questionnaires were posted to participants and, if there was no response, to family physicians. The primary outcome at 2 years was infants' survival without developmental impairment (ie, no disability or problems with behaviour or development). Treatment groups were compared on an intention-to-treat basis. The trial is registered with Controlled-Trials.com, number ISRCTN07249128. FINDINGS: Questionnaires were returned at 2 years for 891 (88%) of 1010 live singleton births (445 of (88%) 503 given NRT and 446 (88%) of 507 given placebo). Because of missing data, developmental outcomes, including four infant deaths, were documented for 888 of (88%) 1010 singleton infants; 445 (88%) of 503 infants in NRT group and 443 (87%) of 507 infants in placebo. In the NRT group, 323 (73%) of 445 infants had no impairment compared with 290 (65%) of 443 infants in the placebo group (odds ratio [OR] 1.40, 95% CI 1.05-1.86, p=0.023). At 2 years, 15 (3%) of 521 mothers in the NRT group and nine (2%) of 529 mothers in the placebo groups self-reported prolonged smoking abstinence since a quit date set in pregnancy (OR 1.71, 95% CI 0.74-3.94, p=0.20). Adverse events were not collected after delivery, but previously reported adverse pregnancy and birth outcomes were similar in the two groups. INTERPRETATION: Infants born to women who used NRT for smoking cessation in pregnancy were more likely to have unimpaired development. NRT had no effect on prolonged abstinence from smoking but did cause a temporary doubling of smoking cessation shortly after randomisation during pregnancy, which could explain findings. If findings are confirmed by subsequent research, this has potential implications for the management of smoking in pregnancy. FUNDING: National Institute for Health Research Health Technology Assessment Programme. PMID- 25127408 TI - Locally linear representation Fisher criterion based tumor gene expressive data classification. AB - Tumor gene expressive data are characterized by a large amount of genes with only a small amount of observations, which always appear with high dimensionality. So it is necessary to reduce the dimensionality before identifying their genre. In this paper, a discriminant manifold learning method, named locally linear representation Fisher criterion (LLRFC), is applied to extract features from tumor gene expressive data. In LLRFC, an inter-class graph and an intra-class graph are constructed based on their genre information, where any tumor gene expressive data in the inter-class graph should select k nearest neighbors with different class labels and in the intra-class graph the k nearest neighbors for any tumor gene expressive data must be sampled from those with the same class. And then the locally least linear reconstruction is introduced to optimize the corresponding weights in both graphs. Moreover, a Fisher criterion is modeled to explore a low dimensional subspace where the reconstruction errors in the inter class graph can be maximized and the reconstruction errors in the intra-class graph can be minimized, simultaneously. Experiments on some benchmark tumor gene expressive data have been conducted with some related algorithms, by which the proposed LLRFC has been validated to be efficient. PMID- 25127409 TI - Automated diagnosis of Age-related Macular Degeneration using greyscale features from digital fundus images. AB - Age-related Macular Degeneration (AMD) is one of the major causes of vision loss and blindness in ageing population. Currently, there is no cure for AMD, however early detection and subsequent treatment may prevent the severe vision loss or slow the progression of the disease. AMD can be classified into two types: dry and wet AMDs. The people with macular degeneration are mostly affected by dry AMD. Early symptoms of AMD are formation of drusen and yellow pigmentation. These lesions are identified by manual inspection of fundus images by the ophthalmologists. It is a time consuming, tiresome process, and hence an automated diagnosis of AMD screening tool can aid clinicians in their diagnosis significantly. This study proposes an automated dry AMD detection system using various entropies (Shannon, Kapur, Renyi and Yager), Higher Order Spectra (HOS) bispectra features, Fractional Dimension (FD), and Gabor wavelet features extracted from greyscale fundus images. The features are ranked using t-test, Kullback-Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance (CBBD), Receiver Operating Characteristics (ROC) curve-based and Wilcoxon ranking methods in order to select optimum features and classified into normal and AMD classes using Naive Bayes (NB), k-Nearest Neighbour (k-NN), Probabilistic Neural Network (PNN), Decision Tree (DT) and Support Vector Machine (SVM) classifiers. The performance of the proposed system is evaluated using private (Kasturba Medical Hospital, Manipal, India), Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) datasets. The proposed system yielded the highest average classification accuracies of 90.19%, 95.07% and 95% with 42, 54 and 38 optimal ranked features using SVM classifier for private, ARIA and STARE datasets respectively. This automated AMD detection system can be used for mass fundus image screening and aid clinicians by making better use of their expertise on selected images that require further examination. PMID- 25127411 TI - Multifunctional 1D magnetic and fluorescent nanoparticle chains for enhanced MRI, fluorescent cell imaging, and combined photothermal/chemotherapy. AB - While the assembled 1D magnetic nanoparticle (NP) chains have demonstrated synergistic magnetic effects from the individual NPs, it is essential to prepare new 1D NP chains that can combine the magnetism with other important material properties for multifunctional applications. This paper reports the fabrication and multifunctional investigation of a new type of 1D NP chains that combine the magnetic properties with fluorescent properties, photothermal conversion ability, and drug carrier function. The building block NPs are composed of magnetic Fe(3)O(4) nanocrystals clustered in the core and fluorescent carbon dots embedded in the mesoporous carbon shell with hydroxyl/carboxyl groups anchored on their surface. These NPs can assemble under the induction of external magnetic field and form stable 1D NP chains of diameter ~ 90 nm and length ~ 3 MUm via the hydrogen bonding and pi-pi stacking linkage of the carbon shell. The resulted 1D hybrid NP chains not only demonstrate much higher magnetic resonance imaging (MRI) contrasting ability than the dispersed building block NPs, but also enter into intracellular region and light up the B16F10 cells under a laser excitation with strong and stable fluorescence. While the mesoporous carbon shell provides high drug loading capacity, the embedded fluorescent carbon dots convert near infrared (NIR) light to heat, and hence kill the tumor cells efficiently and enhance the drug release rate to further improve the therapeutic efficacy under NIR irradiation. Such designed 1D magnetic-fluorescent hybrid NP chains with enhanced MRI contrast, fluorescent imaging ability, and combined chemo /photothermal therapeutic ability have great potential for various biomedical applications. PMID- 25127412 TI - Lactic acid production with undefined mixed culture fermentation of potato peel waste. AB - Potato peel waste (PPW) as zero value byproduct generated from food processing plant contains a large quantity of starch, non-starch polysaccharide, lignin, protein, and lipid. PPW as one promising carbon source can be managed and utilized to value added bioproducts through a simple fermentation process using undefined mixed cultures inoculated from wastewater treatment plant sludge. A series of non-pH controlled batch fermentations under different conditions such as pretreatment process, enzymatic hydrolysis, temperature, and solids loading were studied. Lactic acid (LA) was the major product, followed by acetic acid (AA) and ethanol under fermentation conditions without the presence of added hydrolytic enzymes. The maximum yields of LA, AA, and ethanol were respectively, 0.22 g g(-1), 0.06 g g(-1), and 0.05 g g(-1). The highest LA concentration of 14.7 g L(-1) was obtained from a bioreactor with initial solids loading of 60 g L(-1) at 35 degrees C. PMID- 25127410 TI - The proteasome complex and the maintenance of pluripotency: sustain the fate by mopping up? AB - The proteasome is a multi-enzyme complex responsible for orchestrating protein quality control by degrading misfolded, damaged, abnormal and foreign proteins. Studies related to the association of the proteasomal system in the preservation of self-renewal in both human and mouse pluripotent cells are sparse, and therefore a clear indication of the emergence of a new and important field of research. Under specific conditions the standard proteasome switches to the newly synthesized immunoproteasome, a catalytically active protein chamber also involved in the regulation of protein homeostasis, cell signaling and gene expression. Herein we review recent data to help elucidate and highlight the pivotal role of the proteasome complex, constitutive as well as inducible, in the regulation of self-renewal, pluripotency and differentiation of both embryonic and induced pluripotent stem cells. The proteasome that is endowed with enhanced proteolytic activity maintains self-renewal by regulating gene expression. In addition to protein degradation, the proteasome activator PA28, compartments of the 19S regulatory particle and key members of the ubiquitin pathway dictate the fate of a pluripotent stem cell. We anticipate that our observations will stimulate active research in this new and emerging theme related to stem cell biology, disease and regenerative medicine. PMID- 25127413 TI - Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma. AB - OBJECT: The loss of anatomical landmarks, frequently invasive tumor growth, and tissue changes make transsphenoidal reoperation of nonfunctioning pituitary adenomas (NFAs) challenging. The use of intraoperative MRI (iMRI) may lead to improved results. The goal of this retrospective study was to evaluate the impact of iMRI on transsphenoidal reoperations for NFA. METHODS: Between September 2002 and July 2012, 109 patients underwent reoperations in which 111 transsphenoidal procedures were performed and are represented in this study. A 1.5-T Magnetom Sonata Maestro Class scanner (Siemens) was used for iMRI. Follow-up iMRI scans were acquired if gross-total resection (GTR) was suspected or if no further removal seemed possible. RESULTS: Surgery was performed for tumor persistence and regrowth in 26 (23%) and 85 (77%) patients, respectively. On the initial iMRI scans, GTR was confirmed in 19 (17%) patients. Remnants were located as follows: 65 in the cavernous sinus (71%), 35 in the suprasellar space (38%), 9 in the retrosellar space (10%). Additional resection was possible in 62 (67%) patients, resulting in a significant volume reduction and increased GTR rate (49%). The GTR rates of invasive tumors on initial iMRI and postoperative MRI (poMRI) were 7% and 25%, respectively. Additional remnant resection was possible in 64% of the patients. Noninvasive tumors were shown to be totally resected on the initial iMRI in 31% of cases. After additional resection for 69% of the procedures, the GTR rate on poMRI was 75%. Transcranial surgery to resect tumor remnants was indicated in 5 (5%), and radiotherapy was performed in 29 (27%) patients. After GTR, no recurrence was detected during a mean follow-up of 2.2 +/- 2.1 years. CONCLUSIONS: The use of iMRI in transsphenoidal reoperations for NFA leads to significantly higher GTR rates. It thus prevents additional operations and reduces the number of tumor remnants. The complication rates do not exceed the incidences reported in the literature for primary transsphenoidal surgery. If complete tumor resection is not possible, iMRI guidance can facilitate tumor volume reduction. PMID- 25127414 TI - Association of genetic variants in the retinoblastoma binding protein 6 gene with the risk of glioma: a case-control study in a Chinese Han population. AB - OBJECT: The retinoblastoma binding protein 6 (RBBP6) gene plays an important role in the induction of apoptosis and regulation of the cell cycle, and interacts with both p53 and retinoblastoma protein in carcinogenesis. Recently, many studies investigating the function of the RBBP6 gene, including its roles in lung cancer and breast cancer, have been reported. However, the association between RBBP6 variants and glioma was unknown. Therefore, to uncover the association between single nucleotide polymorphisms (SNPs) of RBBP6 and glioma, a hospital based case-control study was performed in a Chinese Han population. METHODS: Ten common tagging SNPs of the RBBP6 gene (covering 100% of all SNPs) were genotyped with the Sequenom MassARRY iPLEX platform, including 992 cases and 1008 controls, according to the HapMap database based on a pairwise linkage disequilibrium r(2) threshold of 0.8, minor allele frequency of 0.05, and Hardy-Weinberg equilibrium of 0.05. RESULTS: The authors found that 4 SNPs were significantly associated with glioma (rs2033214, p = 0.013, adjusted OR 2.46, 95% CI 1.18-5.14; rs11860248, p = 8.64 * 10-(6), adjusted OR 1.59, 95% CI 1.23-2.05; rs9933544, p = 3.65 * 10(-4), adjusted OR 1.39, 95% CI 1.13-1.87; rs13332653, p = 0.004, adjusted OR 1.49, 95% CI 1.14-1.95). Stratification analyses revealed that rs2033214 was only significantly associated with low-grade gliomas; rs9933544 and rs13332653 were only significantly associated with glioblastoma multiforme; and rs11860248 was significantly associated with both low-grade gliomas and glioblastoma multiforme, compared with the common wild-type homozygous genotype. Further stratified analysis revealed that rs11860248 was more pronounced in certain subgroups: adults, males, histological types, and family history of cancer. What's more, the haplotype and diplotype analyses consistently revealed that the subjects carrying 1 copy of haplotype CCGCC had a 53% increased glioma risk compared with their corresponding noncarriers (p = 0.018, adjusted OR 1.53, 95% CI 1.08-2.17). CONCLUSIONS: The authors' results suggested that RBBP6 gene variants are associated with glioma and contribute to glioma susceptibility, which was first reported elsewhere. Individuals with the so-called risk alleles might have an increased risk of glioma. These results might provide new insight into the occurrence of glioma. PMID- 25127415 TI - Outcome in adult patients with hemorrhagic moyamoya disease after combined extracranial-intracranial bypass. AB - OBJECT: The outcome of patients with hemorrhagic moyamoya disease (MMD) after cerebral revascularization is uncertain. The purpose of this study was to delineate the efficacy of this surgical method in the treatment of hemorrhagic MMD. METHODS: Between January 2007 and August 2011, a consecutive cohort of 113 patients with hemorrhagic MMD was enrolled into this prospective single-center cohort study. The surgical method was combined direct and indirect bypass. The cumulative probability of the primary end point (all stroke and deaths from surgery through 30 days after surgery and ipsilateral recurrent hemorrhage afterward) was analyzed. The angiographic outcome was measured by the following parameters: bypass patency, reduction of basal MMD vessels, improved degree of dilation, and branch extension of the anterior choroidal and posterior communicating arteries (AChA-PCoA). RESULTS: Of the 113 enrolled cases, CT scans revealed pure intraventricular hemorrhage (IVH) in 63 cases (55.7%), pure intracranial hemorrhage (ICH) in 14 cases (12.4%), and ICH with IVH in 36 cases (31.9%). In 74 of 113 hemorrhagic hemispheres (65.5%), the AChA-PCoA was extremely dilated with extensive branches beyond the choroidal fissure. A total of 114 surgeries were performed. No patient suffered ischemic or hemorrhagic stroke through 30 days after surgery. Ipsilateral rebleeding occurred in 5 patients, 4 of whom died of the rebleeding event. The cumulative probability of the primary end point was 0% at 1 year and 1.9% at 2 years. The annual rebleeding rate was 1.87%/person/year. The improvement in AChA-PCoA extension was observed in 75 of 107 operated hemispheres (70.1%), which was higher than that in 7 of 105 unoperated hemispheres (35.2%). CONCLUSIONS: Revascularization may provide a benefit over conservative therapy for hemorrhagic MMD patients. The improvement of dilation and branch extension of AChA-PCoA might be correlated with the low rebleeding rate. PMID- 25127416 TI - Practical surgical indicators to identify candidates for radical resection of insulo-opercular gliomas. AB - OBJECT: Maximum resection of gliomas with minimum surgical complications usually leads to optimum outcomes for patients. Radical resection of insulo-opercular gliomas is still challenging, and selection of ideal patients can reduce risk and obtain better outcomes. METHODS: This retrospective study included 83 consecutively treated patients with newly diagnosed gliomas located at the insulo opercular region and extending to the sylvian fissure around the primary motor and somatosensory cortices. The authors selected 4 characteristics as surgical indicators: clear tumor boundaries, negative enhancement, intact lenticulostriate arteries, and intact superior extremity of the central insular sulcus. RESULTS: Univariate analysis showed that tumors with clear boundaries were associated with higher rates of gross-total resection than were tumors with ambiguous boundaries (75.7% vs 19.6%). Tumors with negative enhancement compared with enhanced tumors were associated with lower frequency of tumor progression (32.0% vs 81.8%, respectively) and lower rates of surgical complications (14.0% vs 45.5%, respectively). Tumors with intact lenticulostriate arteries were associated with higher rates of gross-total resection than were tumors with involved lenticulostriate arteries (67.3% vs 11.8%, respectively). Tumors with intact superior extremity of the central insular sulcus were associated with higher rates of gross-total resection (57.4% vs 20.7%, respectively) and lower rates of surgical complications (18.5% vs 41.4%, respectively) than were tumors with involved anatomical structures. Multivariate analysis showed that clear tumor boundaries were independently associated with gross-total resection (p < 0.001). Negative enhancement was found to be independently associated with surgical complications (p = 0.005), overall survival times (p < 0.001), and progression free survival times (p = 0.004). Independent associations were also found between intact lenticulostriate arteries and gross-total resection (p < 0.001), between intact lenticulostriate arteries and progression-free survival times (p = 0.026), and between intact superior extremity of the central insular sulcus and gross total resection (p = 0.043). Among patients in whom all 4 indicators were present, prognosis was good (5-year survival rate 93.3%), resection rate was maximal (gross-total resection 100%), and surgical complication rate was minimal (6.7%). Also among these patients, overall rates of survival (p = 0.003) and progression-free survival (p = 0.005) were significantly higher than among patients in whom fewer indicators were present. CONCLUSIONS: The authors propose 4 simple indicators that can be used to identify ideal candidates for radical resection of insulo-opercular gliomas, improve the outcomes, and promote maximum resection without introducing neurological complications. The indicators are clear tumor boundaries, negative enhancement, intact lenticulostriate arteries, and intact superior extremity of the central insular sulcus. PMID- 25127417 TI - National socioeconomic indicators are associated with outcomes after aneurysmal subarachnoid hemorrhage: a hierarchical mixed-effects analysis. AB - OBJECT: Although heterogeneity exists in patient outcomes following subarachnoid hemorrhage (SAH) across different centers and countries, it is unclear which factors contribute to such disparities. In this study, the authors performed a post hoc analysis of a large international database to evaluate the association between a country's socioeconomic indicators and patient outcome following aneurysmal SAH. METHODS: An analysis was performed on a database of 3552 patients enrolled in studies of tirilazad mesylate for aneurysmal SAH from 1991 to 1997, which included 162 neurosurgical centers in North and Central America, Australia, Europe, and Africa. Two primary outcomes were assessed at 3 months after SAH: mortality and Glasgow Outcome Scale (GOS) score. The association between these outcomes, nation-level socioeconomic indicators (percapita gross domestic product [GDP], population-to-neurosurgeon ratio, and health care funding model), and patientlevel covariates were assessed using a hierarchical mixed-effects logistic regression analysis. RESULTS: Multiple previously identified patient-level covariates were significantly associated with increased mortality and worse neurological outcome, including age, intraventricular hemorrhage, and initial neurological grade. Among national-level covariates, higher per-capita GDP (p < 0.05) was associated with both reduced mortality and improved neurological outcome. A higher population-to-neurosurgeon ratio (p < 0.01), as well as fewer neurosurgical centers per population (p < 0.001), was also associated with better neurological outcome (p < 0.01). Health care funding model was not a significant predictor of either primary outcome. CONCLUSIONS: Higher per-capita gross GDP and population-to-neurosurgeon ratio were associated with improved outcome after aneurysmal SAH. The former result may speak to the availability of resources, while the latter may be a reflection of better outcomes with centralized care. Although patient clinical and radiographic phenotypes remain the primary predictors of outcome, this study shows that national socioeconomic disparities also explain heterogeneity in outcomes following SAH. PMID- 25127418 TI - Monkey-adapted HIV-1 highlights in vivo significance of restriction factors. AB - HIV-1 was isolated 31 years ago, yet models for studying HIV-1 pathogenesis in vivo are still lacking. Recent experiments using an HIV-1 strain engineered to replicate in macaques recapitulate several important features of human AIDS, and provide insight into the genetics of cross-species transmission and emergence of pathogenic retroviruses. PMID- 25127420 TI - Catalytic olefin hydroamination with aminium radical cations: a photoredox method for direct C-N bond formation. AB - While olefin amination with aminium radical cations is a classical method for C-N bond formation, catalytic variants that utilize simple 2 degrees amine precursors remain largely undeveloped. Herein we report a new visible-light photoredox protocol for the intramolecular anti-Markovnikov hydroamination of aryl olefins that proceeds through catalytically generated aminium radical intermediates. Mechanistic studies are consistent with a process involving amine oxidation via electron transfer, turnover-limiting C-N bond formation, and a second electron transfer step to reduce a carbon-centered radical, rendering the overall process redox-neutral. A range of structurally diverse N-aryl heterocycles can be prepared in good to excellent yields under conditions significantly milder than those required by conventional aminium-based protocols. PMID- 25127421 TI - The Importance of Sleep: Attentional Problems in School-Aged Children With Down Syndrome and Williams Syndrome. AB - In typically developing (TD) children, sleep problems have been associated with day-time attentional difficulties. Children with developmental disabilities often suffer with sleep and attention problems, yet their relationship is poorly understood. The present study investigated this association in school-aged children with Down syndrome (DS) and Williams syndrome (WS). Actigraphy and pulse oximetry assessed sleep and sleep-disordered breathing respectively, and attention was tested using a novel visual Continuous Performance Task (CPT).Attentional deficits were evident in both disorder groups. In the TD group, higher scores on the CPT were related to better sleep quality, higher oxyhemoglobin saturation (SpO2), and fewer desaturation events. Sleep quality, duration, and SpO2 variables were not related to CPT performance for children with DS and WS. PMID- 25127422 TI - Oxidative coupling of terminal alkyne with alpha-hydroxy ketone: an expedient approach toward ynediones. AB - An efficient and mild copper-catalyzed one-pot approach toward ynediones has been established. A variety of ynediones were constructed directly through oxidative coupling of alkyne with alpha-hydroxy ketone. Oxygen-oxidizing and neutral conditions in one-pot for a wide range of substrates including natural product derivatives make this transformation highly efficient and practical. On the basis of control experiments, in situ IR measurements, and isotopic labeling experiments, a plausible mechanism involving intermediate phenylglyoxal was drawn. Applications by synthesis of various heterocycles were also investigated. PMID- 25127419 TI - Characterizing solution surface loop conformational flexibility of the GM2 activator protein. AB - GM2AP has a beta-cup topology with numerous X-ray structures showing multiple conformations for some of the surface loops, revealing conformational flexibility that may be related to function, where function is defined as either membrane binding associated with ligand binding and extraction or interaction with other proteins. Here, site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy and molecular dynamic (MD) simulations are used to characterize the mobility and conformational flexibility of various structural regions of GM2AP. A series of 10 single cysteine amino acid substitutions were generated, and the constructs were chemically modified with the methanethiosulfonate spin label. Continuous wave (CW) EPR line shapes were obtained and subsequently simulated using the microscopic order macroscopic disorder (MOMD) program. Line shapes for sites that have multiple conformations in the X-ray structures required two spectral components, whereas spectra of the remaining sites were adequately fit with single-component parameters. For spin labeled sites L126C and I66C, spectra were acquired as a function of temperature, and simulations provided for the determination of thermodynamic parameters associated with conformational change. Binding to GM2 ligand did not alter the conformational flexibility of the loops, as evaluated by EPR and NMR spectroscopies. These results confirm that the conformational flexibility observed in the surface loops of GM2AP crystals is present in solution and that the exchange is slow on the EPR time scale (>ns). Furthermore, MD simulation results are presented and agree well with the conformational heterogeneity revealed by SDSL. PMID- 25127423 TI - Virulence attributes in Brazilian clinical isolates of Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is an opportunistic human pathogen responsible for causing a huge variety of acute and chronic infections with significant levels of morbidity and mortality. Its success as a pathogen comes from its genetic/metabolic plasticity, intrinsic/acquired antimicrobial resistance, capacity to form biofilm and expression of numerous virulence factors. Herein, we have analyzed the genetic variability, antimicrobial susceptibility as well as the production of metallo-beta-lactamases (MBLs) and virulence attributes (elastase, pyocyanin and biofilm) in 96 strains of P. aeruginosa isolated from different anatomical sites of patients attended at Brazilian hospitals. Our results revealed a great genetic variability, in which 86 distinct RAPD types (89.6% of polymorphisms) were detected. Regarding the susceptibility profile, 48 strains (50%) were resistant to the antimicrobials, as follows: 22.92% to the three tested antibiotics, 12.5% to both imipenem and meropenem, 11.46% to ceftazidime only, 2.08% to imipenem only and 1.04% to both ceftazidime and meropenem. Out of the 34 clinical strains of P. aeruginosa resistant to both imipenem and meropenem, 25 (73.53%) were MBL producers by phenotypic method while 12 (35.29%) were PCR positive for the MBL gene SPM-1. All P. aeruginosa strains produced pyocyanin, elastase and biofilm, although in different levels. Some associations were demonstrated among the susceptibility and/or production of these virulence traits with the anatomical site of strain isolation. For instance, almost all strains isolated from urine (85.71%) were resistant to the three antibiotics, while the vast majority of strains isolated from rectum (95%) and mouth (66.67%) were susceptible to all tested antibiotics. Urine isolates produced the highest pyocyanin concentration (20.15+/-5.65 MUg/ml), while strains isolated from pleural secretion and mouth produced elevated elastase activity (1441.43+/-303.08 FAU) and biofilm formation (OD590 0.676+/-0.32), respectively. Also, MBL-positive strains produced robust biofilm compared to MBL-negative strains. Collectively, the production of site-dependent virulence factors can be highlighted as potential therapeutic targets for the treatment of infections caused by heterogeneous and resistant strains of P. aeruginosa. PMID- 25127424 TI - Matrix-assisted laser desorption ionization-time of flight mass spectrometry assigns Escherichia coli to the phylogroups A, B1, B2 and D. AB - Escherichia coli classification into phylogroups reflects the diversity of their pathogenicity and their ecological niche, B2 isolates being the most virulent among extra-intestinal strains. MALDI-TOF MS allows a quick, automated, simple and inexpensive bacterial identification. We evaluated the MALDI-TOF MS as a tool for E. coli phylogroup differentiation. We used 656 E. coli isolates, previously assigned to phylogroup A, B1, B2, and D by multiplex PCR, to constitute independent training and validation sets. We then defined two phylogrouping strategies, both validated on spectra obtained by the 'direct transfer method'. The first strategy used the MALDI Biotyper software (Bruker Daltonik) that identified a single peak shift between isolates of phylogroup B2 and those of groups A, B1 and D. It accurately classified 89% of the isolates. The second strategy used the ClinProTools software (Bruker Daltonik) and was based on three successive models. The model 1 adequately differentiated 92% of phylogroup B2 isolates from those belonging to phylogroups A, B1, D. The model 2 adequately discriminated 87% of phylogroup D-isolates from those of phylogroups A and B1. The model 3 correctly sorted 69% of A and B1-isolates. We concluded that clinical laboratories could routinely and very quickly assign E. coli isolates to phylogroups with MALDI-TOF MS. These methods could (i) expedite the detection of the most virulent strains belonging to phylogroup B2 and (ii) be a first-line tool to monitor the epidemiology of extra-intestinal pathogenic E. coli. PMID- 25127425 TI - New insights into highly efficient reduction of CO2 to formic acid by using zinc under mild hydrothermal conditions: a joint experimental and theoretical study. AB - We report here a theoretical study with quantum chemical calculations based on experimental results to understand highly efficient reduction of CO2 to formic acid by using zinc under hydrothermal conditions. Results showed that zinc hydride (Zn-H) is a key intermediate species in the reduction of CO2 to formic acid, which demonstrates that the formation of formic acid is through an SN2-like mechanism. PMID- 25127427 TI - Advances in understanding the mechanism of zebrafish heart regeneration. AB - The adult mammalian heart was once believed to be a post-mitotic organ without any capacity for regeneration, but recent findings have challenged this dogma. A modified view assigns the mammalian heart a measurable capacity for regeneration throughout its lifetime, with the implication that endogenous regenerative capacity can be therapeutically stimulated in the injury setting. Although extremely limited in adult mammals, the natural capacity for organ regeneration is a conserved trait in certain vertebrates. Urodele amphibians and teleosts are well-known examples of such animals that can efficiently regenerate various organs including the heart as adults. By understanding how these animals regenerate a damaged heart, one might obtain valuable insights into how regeneration can be augmented in injured human hearts. Among the regenerative vertebrate models, the teleost zebrafish, Danio rerio, is arguably the best characterized with respect to cardiac regenerative responses. Knowledge is still limited, but a decade of research in this model has led to results that may help to understand how cardiac regeneration is naturally stimulated and maintained. This review surveys recent advances in the field and discusses current understanding of the endogenous mechanisms of cardiac regeneration in zebrafish. PMID- 25127429 TI - Spinal dural arteriovenous fistula: correlation between radiological and clinical findings. AB - OBJECT: The pathophysiology of spinal dural arteriovenous fistulas (SDAVFs) results in perimedullary venous congestion and in turn central cord congestion. Clinically, this presents with progressive neurological dysfunctions that, if diagnosed in a timely fashion, can be at least halted and in part reversed. In SDAVFs, imaging features on MRI and digital subtraction angiography (DSA) have not been studied in conjunction with clinical findings. The primary purpose of the present study was to test if severity of clinical presentation varies in relation to imaging. METHODS: This retrospective cohort study identified 12 patients treated for SDAVF at the authors' institution. The extent of venous congestion and cord edema was quantified by the number of vertebral levels shown to be affected on DSA and MRI. A modified Aminoff-Logue Scale (ALS) score was assigned at the time of diagnosis and again after definitive therapy. The patients were divided into one of two groups: those with venous congestion < 7 and >= 7 vertebral levels seen on DSA and MRI and with central cord edema < 6 and >= 6 levels. A t-test was used to assess for a difference in the presenting ALS score between the groups. RESULTS: Patients with >= 7 levels of venous congestion reported greater functional disability (DSA: p <= 0.001, Cohen's d = 0.509; and MRI: p <= 0.001, d = 0.632). Patients with a greater extent of cord edema also reported worse functional disability (p <= 0.001, d = 2.31). There was a strong linear correlation between the post- and pretreatment ALS scores (R(2) = 0.86) for those with successful interventions (n = 9). CONCLUSIONS: In patients with an SDAVF, the severity of the neurological dysfunction may be predicted by the extent of DSA- and MRI-documented venous congestion and cord edema. There was a strong positive relationship between initial and posttreatment neurological dysfunction. PMID- 25127430 TI - Long-term patient outcomes after posterior cervical foraminotomy: an analysis of 151 cases. AB - OBJECT: The authors conducted a study to investigate the rate and timing of reoperation due to symptom recurrence after unilateral posterior cervical foraminotomy (PCF). METHODS: The authors retrospectively reviewed demographic, surgical, and clinical data from 151 patients who underwent unilateral PCF at their institution with an average follow-up of 4.15 years. The main outcome variables were reoperation rate, time to reoperation, and short- and long-term radiculopathy improvement rates. Kaplan-Meier analyses were conducted to assess risk of reoperation and recurrence of radiculopathy over time. RESULTS: After index PCF in 151 patients, the overall reoperation rate was 9.9% (15 patients). The average time until reoperation was 2.4 years, and the average last follow-up examination was 4.15 years after the first surgery. Patients who presented with preoperative neck pain in addition to radiculopathy had a higher risk for reoperation and a shorter time to reoperation. The majority of patients who underwent a reoperation had an anterior cervical discectomy and fusion (80%). A smaller number of patients had reoperation that included a repeat PCF (6.7%) or laminectomy with posterior cervical fusion (13.3%). The rate of same-level reoperation (6.6%, 10 patients) was significantly higher (p = 0.05) when compared with adjacent-segment (1.3%, 2 patients) or distant-segment (1.9%, 3 patients) reoperation. At last follow-up, the overall rate of improvement in radiculopathy was 85%, with the majority of patients (91.4%) experiencing resolution as early as 1 month after index surgery. Following the subgroup that experienced initial symptom improvement, 16.1% of these patients experienced radiculopathy recurrence an average of 7.3 years after the initial operation. While the reoperation rate for the overall cohort in this series was 9.9%, patients with follow-up periods longer than 2 years had a reoperation rate of 18.3%. Moreover, patients with more than 10 years of follow-up had a reoperation rate of 24.3%. CONCLUSIONS: PCF is a procedure performed to address nerve root compression in the cervical spine. The authors evaluated 151 patients who underwent unilateral PCF and found a reoperation rate of 9.9% at an average of 2.4 years after the initial surgery (6.6% at same level, 3.3% elsewhere). The reoperation rates reached 18.3% and 24.3% in patients with follow-up periods longer than 2 and 10 years, respectively. The authors' analysis revealed that patients with no preoperative neck pain had the lowest rates of revision surgery after PCF. PMID- 25127426 TI - 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). PMID- 25127431 TI - Computed tomography-guided epidural patching of postoperative cerebrospinal fluid leaks. AB - OBJECT: Cerebrospinal fluid leaks due to unrecognized durotomy during spinal surgery are often managed with a second surgery for dural closure. CT-guided percutaneous patching targeted to the dural defect offers an alternative to surgery since it can be performed in a minimally invasive fashion without the need for general anesthesia. This case series describes the authors' experience using targeted CT-guided percutaneous patching to repair incidental durotomies incurred during spinal surgery. METHODS: This investigation is a retrospective case series involving patients who underwent CT-guided percutaneous patching of surgical incidental durotomies and were referred between January 2007 and June 2013. Their presenting clinical history, myelographic findings, and clinical outcomes, including the need for eventual surgical duraplasty, were reviewed. RESULTS: Nine cases were identified, including 7 durotomies incurred during lumbar discectomy, one due to a medial transpedicular screw breach, and one incurred during vertebrectomy for spinal osteosarcoma. All patients who had favorable outcomes with percutaneous intervention alone had 2 common features: dural defect of 4 mm or smaller and absence of a pseudomeningocele. Patients with CSF leaks complicated by pseudomeningocele and those with a dural defect of 6 mm or more all required eventual surgical management. CONCLUSIONS: The authors' results suggest that findings on CT myelography may help predict which patients with postsurgical durotomy can be treated with percutaneous intervention. In particular, CT-guided patching may be more likely to be successful in those patients with dural defects of less than 5 mm and without pseudomeningocele. In patients with larger dural defects or pseudomeningoceles, percutaneous blood patching alone is unlikely to be successful. PMID- 25127432 TI - Utility of routine biopsy at vertebroplasty in the management of vertebral compression fractures: a tertiary center experience. AB - OBJECT: The authors assess the utility of routine biopsy at vertebroplasty for vertebral compression fracture (VCF) as a tool in the early detection of malignancy in presumed benign VCF. METHODS: A prospective observational study was conducted on a cohort of consecutive patients undergoing vertebroplasty over a 5 year period between April 2006 and March 2011 at the Royal London Hospital. Polymethylmethacrylate cement injection was used in every procedure. Intraoperative vertebral body biopsy was performed routinely at every level of VCF. Pain visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores, analgesic usage, and complications were recorded preoperatively and at 1 day, 1 week, 1 month, 6 months, and 1 year postoperatively. RESULTS: A total of 202 levels were augmented in 147 patients. The most common levels augmented were T-12 (17%), L-1 (18%), and L-4 (10%). Analysis of 184 routine vertebral biopsies in 135 patients revealed that in 86 patients with presumed osteoporosis and no prior cancer diagnosis, 4 (4.7%) had a malignant VCF. In 20 known cancer patients presumed to be in remission, 2 (10%) had a malignant VCF. Routine vertebral biopsy returned an overall cancer diagnosis rate of 5.5% (6 of 109) when combining the 2 groups (patients with no prior history of cancer or cancer thought to be in remission). In these 6 patients, history, examination, laboratory tests, and preprocedure imaging all failed to suggest malignancy diagnosed at routine biopsy. Significant reductions in pain VAS and ODI scores were evident at Day 1 and were sustained at up to 1 year postoperatively (p < 0.001). They were not dependent on the level of fracture (T3-10, T11-L2, or L3 S1) (p > 0.05), number of levels treated (single level, 2 levels, or > 2 levels) (p > 0.05), or etiology of VCF (p > 0.05). The complication rate was 6% (9 of 147). There were 5 deaths, none of which were directly related to surgery. CONCLUSIONS: Routine vertebral biopsy performed at vertebroplasty may demonstrate cancer-related VCFs in unsuspected patients with no previous cancer diagnosis or active malignancy in patients previously thought to be in remission. This early diagnosis of cancer or relapsed disease will play an important role in expediting patients' subsequent cancer management. In cases of multiple-level VCF, the authors advocate biopsy at each level to maximize the diagnostic yield from the specimens and to avoid missing a malignancy at a single level. PMID- 25127433 TI - Progression of ossification of the posterior longitudinal ligament of the thoracic spine following posterior decompression and stabilization. AB - OBJECT: Despite its potential clinical impact, information regarding progression of thoracic ossification of the posterior longitudinal ligament (OPLL) is scarce. Posterior decompression with stabilization is currently the primary surgical treatment for symptomatic thoracic OPLL; however, it remains unclear whether thoracic OPLL increases in size following spinal stabilization. It is also unknown whether patients' clinical symptoms worsen as OPLL size increases. In this retrospective case series study, the authors examined the postoperative progression of thoracic OPLL. METHODS: Nine consecutive patients with thoracic OPLL who underwent posterior decompression and fixation with a minimum follow-up of 3 years were included in this study. Thin-slice CT scans of the thoracic spine obtained at the time of surgery and the most recent follow-up were analyzed. The level of the most obvious protrusion of ossification was determined using the sagittal reconstructions, and the ossified area was measured on the axial reconstructed scan at the level of the most obvious protrusion of ossification using the DICOM (digital imaging and communications in medicine) software program. Myelopathy severity was assessed according to the Japanese Orthopaedic Association (JOA) scale score for lower-limb motor function on admission, at postoperative discharge, and at the last follow-up visit. RESULTS: The OPLL area was increased in all patients. The mean area of ossification increased from 83.6 +/- 25.3 mm(2) at the time of surgery to 114.8 +/- 32.4 mm(2) at the last follow up visit. No patients exhibited any neurological deterioration due to OPLL progression. CONCLUSIONS: The present study demonstrated that the size of the thoracic OPLL increased after spinal stabilization. Despite diminished local spinal motion, OPLL progression did not decrease or stop. Physicians should pay attention to ossification progression in patients with thoracic OPLL. PMID- 25127434 TI - Targeted structure modulation of "pillar-layered" metal-organic frameworks for CO2 capture. AB - Two new zinc MOFs with similar "pillar-layered" framework structures based on 1,1'-biphenyl-2,2',6,6'-tetracarboxylic acid (H4bpta) and two different bipyridine pillar ligands, namely {[Zn4(bpta)2(4-pna)2(H2O)2].4DMF.3H2O}n (1) and {[Zn2(bpta)(bpy-ea)(H2O)].2DMF.H2O}n (2) (4-pna = N-(4-pyridyl)isonicotinamide and bpy-ea = 1,2-bis(4-pyridyl)ethane), have been synthesized and investigated with their CO2 adsorption properties. By analysis of the structure properties and the CO2 adsorption performances of these two MOFs, it was found that the introduction of polar acylamide groups via 4-pna resulted in 1 with enhanced CO2 capacity and CO2/CH4 selectivity at low pressure. In contrast, the framework of 2 shows flexible properties originating from the flexibility of the ethanediylidene group in the bpy-ea ligand, which benefits the sieve effect of pores to give higher CO2/CH4 selectivity at a relatively high pressure range. PMID- 25127435 TI - The role of serum soluble urokinase-type plasminogen activator receptor in stable chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) results from an abnormal inflammatory response of the lungs to noxious particles or gases. Serum soluble urokinase-type plasminogen activator receptor (suPAR) is a glycoprotein secreted during infections and inflammation. The main goal of this study was to evaluate the serum suPAR level in stable COPD patients compared with a control group. METHODS: Forty-six stable COPD patients and 41 control subjects were included in the study. Blood samples were collected from 46 stable COPD patients (40 men, 6 women; mean [SD] age, 55.92 [7.91] years; the forced expiratory volume in 1 second, 45.32% [19.1%] of predicted). Forty-one healthy subjects were selected as control subjects and were matched to COPD patients with respect to age and body mass index. Serum suPAR and plasma fibrinogen levels were measured in stable COPD patients and control subjects. RESULTS: Serum suPAR levels of the COPD patients were significantly higher than those of the control subjects (4.94 [2.79] and 2.40 [2.01] ng/mL, respectively; P < 0.001). Plasma fibrinogen levels of the COPD patients were significantly higher than those of the control subjects (406.77 [172.6] and 336.53 [96.1] g/L, respectively; P < 0.05). CONCLUSIONS: Our study indicated that serum suPAR may play an important role in the inflammatory process of COPD, and this increase may be particularly large for patients in Global Initiative for Chronic Obstructive Lung Disease stages III and IV. Serum suPAR and plasma fibrinogen level measurements may be useful for the evaluation of stable COPD. PMID- 25127436 TI - Little adjustments significantly improve the Turkevich synthesis of gold nanoparticles. AB - In this report, we show how the classical and widely used Turkevich synthesis can be improved significantly by simple adjustments. The gold nanoparticles (AuNPs) produced with the optimized protocol have a much narrower size distribution (5-8% standard deviation), and their diameters can be reproduced with unrivaled little variation (<3%). Moreover, large volumes of these particles can be produced in one synthesis; we routinely synthesize 1000 mL of ~3.5 nM AuNPs. The key features of the improved protocol are the control of the pH by using a citrate buffer instead of a citrate solution as the reducing agent or stabilizer and optimized mixing of reagents. Further, the shape uniformity of the particles can be improved by addition of 0.02 mM EDTA. While the proposed protocol is as straightforward as the original Turkevich protocol, it is more tolerant against variations in precursor concentration. PMID- 25127438 TI - Spinal cord--skeletal muscle cocultures detect muscle-relaxant action of botulinum neurotoxin A. AB - The mouse LD50 assay is routinely used for potency testing of botulinum toxins. Unfortunately, this test is associated with severe pain and distress in animals and requires large quantities of mice. Here we used cocultures of spinal cord and muscle tissue as an alternative for probing botulinum toxins. Cocultures were prepared from mouse embryonic tissue (C57/BL6J) and cultured for 24-27 days. In these cultures spontaneous muscle activity was quantified in sham- and botulinum toxin-treated cultures for up to 3 days by video microscopy. At a concentration of 58 fmol/L or higher, incobotulinumtoxin A significantly reduced the frequency of muscle contractions within 24 hours after incubation. Hence, nerve-muscle cultures are similar sensitive as the mouse LD50 assay. The limit of detection, as observed in our study, is close to the most sensitive cell-based bioassays, capable to detect concentrations of botulinum neurotoxin A between 30 and 50 fmol/L. However, spontaneous muscle activity of individual cultures displayed considerable fluctuations when evaluated on a day-to-day basis. Generally, the authors would like to emphasize, that in its present form, this in vitro assay might be too laborious for botulinum toxin potency testing. Thus, methodical improvements to decrease data variability are the next milestone to be passed towards developing this model into an assay that can be utilized for reducing animal experimentation. PMID- 25127437 TI - Incense use and cardiovascular mortality among Chinese in Singapore: the Singapore Chinese Health Study. AB - BACKGROUND: Incense burning is common in many parts of the world. Although it is perceived that particulate matter from incense smoke is deleterious to health, there is no epidemiologic evidence linking domestic exposure to cardiovascular mortality. OBJECTIVE: We examined the association between exposure to incense burning and cardiovascular mortality in the Singapore Chinese Health Study. METHODS: We enrolled a total of 63,257 Singapore Chinese 45-74 years of age during 1993-1998. All participants were interviewed in person to collect information about lifestyle behaviors, including the practice of burning incense at home. We identified cardiovascular deaths via record linkage with the nationwide death registry through 31 December 2011. RESULTS: In this cohort, 76.9% were current incense users, and most of the current users (89.9%) had burned incense daily for >= 20 years. Relative to noncurrent users, current users had a 12% higher risk of cardiovascular mortality [multivariable adjusted hazard ratio (HR) = 1.12; 95% CI: 1.04, 1.20]. The HR was 1.19 (95% CI: 1.03, 1.37) for mortality due to stroke and 1.10 (95% CI: 1.00, 1.21) for mortality due to coronary heart disease. The association between current incense use and cardiovascular mortality appeared to be limited to participants without a history of cardiovascular disease at baseline (HR = 1.16; 95% CI: 1.07, 1.26) but not linked to those with a history (HR = 1.00; 95% CI: 0.86, 1.17). In addition, the association was stronger in never-smokers (HR = 1.12; 95% CI: 1.02, 1.23) and former smokers (HR = 1.19; 95% CI: 1.00, 1.42) than in current smokers (HR = 1.05; 95% CI: 0.91, 1.22). CONCLUSIONS: Long-term exposure to incense burning in the home environment was associated with an increased risk of cardiovascular mortality in the study population. PMID- 25127439 TI - Laparoscopic sleeve gastrectomy in morbidly obese patients with end-stage heart failure and left ventricular assist device: medium-term results. AB - BACKGROUND: Morbid obesity precludes patients with end-stage heart failure from becoming cardiac transplant candidates. This study evaluates the safety and efficacy of laparoscopic sleeve gastrectomy (LSG) as a means to transplant candidacy in such patients. METHODS: Morbidly obese patients with end-stage heart failure, who were ineligible for cardiac transplantation and underwent LSG between 2008 and 2013, were reviewed retrospectively. Demographic characteristics, perioperative details, percentage of excess weight loss (%EWL), and status of transplant candidacy were analyzed. RESULTS: Six patients (3 men) with end-stage heart failure and morbid obesity underwent LSG. Three patients (50%) had a left ventricular assist device (LVAD) in place at the time of surgery. Median age was 34 (31-66) years and mean preoperative body mass index (BMI) was 47.6+/-3.0 kg/m2. Median operative time was 90 (66-141) minutes, with a median length of stay of 7 (4-16) days. There were no perioperative deaths. One patient suffered a spontaneous flank hematoma. The same patient also had thrombosis of the LVAD pump at 3 weeks postoperatively, requiring an uneventful device exchange. At median follow-up of 22 (12-70) months, the mean %EWL was 51.4+/-10.3% with a decrease in BMI to 34.3+/-2.4 kg/m2 (P<.05). All patients had lost sufficient weight to become transplant eligible within 12 months of surgery. Two patients had undergone successful transplantation and another 2 were on the transplant list. CONCLUSION: LSG appears to be a safe, technically feasible, and effective method for obtaining adequate weight loss in morbidly obese patients with end-stage heart failure and mechanical circulatory support, subsequently improving their access to cardiac transplantation. This is the largest case series to date of this high-risk group of patients undergoing LSG. PMID- 25127440 TI - Correlation of impaired subjective visual vertical and postural instability in Parkinson's disease. AB - Perception of verticality is essential for postural control. On the other hand, postural instability is one of the cardinal features in Parkinson's disease (PD). Thus, the objective of this study was to evaluate the vertical perception using the subjective visual vertical test in PD patients with different degrees of postural instability and in different stages of disease. Forty five idiopathic PD patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr Scale, the clinical test for postural instability, and the subjective visual vertical test. Forty-five healthy individuals were evaluated in the control group. PD patients had a compromised perception of verticality and a disturbed processing of graviceptive pathways. Good correlation was also found between subjective visual vertical and postural instability. Patients with the worst postural instability had greater deviations of subjective visual vertical. There was also a positive correlation between subjective visual vertical and scores on the UPDRS and Hoehn and Yahr Scale, with good and reasonable degree of intensity, respectively. These findings suggest that the perception of verticality is affected in PD patients and this abnormal vertical perception and disturbed processing of graviceptive pathways are associated with postural instability and to a lesser degree with disease severity. PMID- 25127441 TI - Dementia is associated with iron-deficiency anemia in females: a population-based study. AB - Cognitive derangement and neurological symptoms are observed in patients with anemia. Although it is still controversial, a few studies suggested that anemia may increase the risk of dementia. This study aimed to explore the association between iron-deficiency anemia (IDA) and dementia in a population-based case control study. We retrieved our study sample from the Taiwan Longitudinal Health Insurance Database 2000. We extracted 8300 subjects with a diagnosis of dementia and 8300 age- and gender-matched controls. The results showed that there was a significant difference in the prevalence of prior IDA between cases and controls (6.0% vs. 3.8%, p<0.001). The conditional logistic regression analysis suggested that the odds ratio (OR) of prior IDA for cases was 1.36 (95% CI: 1.07-1.74) compared to controls after adjusting for subjects' monthly income, geographic location, urbanization level, hyperlipidemia, diabetes, hypertension, and alcohol abuse. Among female subjects, the adjusted OR of prior IDA for cases was as high as 2.00 (95% CI: 1.42-2.80) compared to controls. However, in men-no increased odds of prior IDA were observed, compared to controls. We concluded that women with dementia had a higher prevalence of prior IDA, compared to controls. PMID- 25127442 TI - Quality of life after total and subtotal gastrectomy for gastric carcinoma. AB - BACKGROUND: There remains debate as to whether quality of life (QoL) is better for patients following sub-total gastrectomy (SG) or total gastrectomy (TG) for cancer. Both have similar survival rates provided an R0 resection is performed and in many series the morbidity and mortality after TG is higher than SG. The aim of this study was to evaluate the QoL in patients after TG and SG for cancer. METHOD: All surviving patients who had undergone TG or SG between 1994 and 2009 were identified from a prospectively collected database and sent the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ C30 v.3) and the gastric module (QLQ-STO22). RESULTS: From a total of 261 patients who had undergone TG or SG in the study period, 91 were still alive and 53 responded. There was no significant difference between the QoL between TG and SG based on functional scales and global health status. However dysphagia and eating restrictions were significantly worse in the TG group. CONCLUSION: This study has demonstrated that there is no difference in overall QoL in patients with TG or SG although eating restrictions and dysphagia are worse after TG. PMID- 25127443 TI - Effects of different types of N deposition on the fungal decomposition activities of temperate forest soils. AB - Nitrogen (N) deposition significantly affects soil microbial activities and litter decomposition processes in forest ecosystems. However, the changes in soil fungi during litter decomposition remain unclear. In this study, ammonium nitrate was selected as inorganic N (IN), whereas urea and glycine were selected as organic N (ON). N fertilizer with different IN-to-ON ratios (1:4, 2:3, 3:2, 4:1, and 5:0) was mixed in equal amounts and then added to temperate forest soils. Half of each treatment was simultaneously added with streptomycin to inhibit soil bacteria. The activities of enzymes involved in litter decomposition (invertase, beta-glucosidase, cellulase, polyphenol oxidase, and phosphatase) were assayed after a three-year field experiment. The results showed that enzymatic activities were inhibited by IN addition but accelerated by ON addition in the non antibiotic addition treatments. An increase in ON in the mixed N fertilizer also shifted enzymatic activities from N inhibition to N stimulation. Similarly, in the antibiotic addition treatments, fungal activities revealed the same trends, but they were seriously inhibited by IN and significantly accelerated by ON. These results indicated that soil fungi were more sensitive to N deposition, particularly to ON. A large amount of ON may convert soil microbial communities into a fungi-dominated system. However, excessive ON deposition (20% IN+80% ON) caused N saturation and repressed fungal activities. These results suggested that soil fungi were sensitive to N type and that different IN-to-ON ratios may induce diverse ecological effects on soil fungi. PMID- 25127444 TI - Socioeconomic development as a determinant of the levels of organochlorine pesticides and PCBs in the inhabitants of Western and Central African countries. AB - Several studies of environmental samples indicate that the levels of many persistent organic pollutants (POPs) are increasing in Africa, but few studies have been conducted in humans. Simultaneously, many African countries are experiencing a rapid economic growth and implementing information and communication technologies (ICT). These changes have generated high amounts of electronic waste (e-waste) that have not been adequately managed. We tested the hypothesis that the current levels of two main classes of POPs in Western and Central African countries are affected by the degree of socioeconomic development. We measured the levels of 36 POPs in the serum of recent immigrants (N=575) who came from 19 Sub-Saharan countries to the Canary Islands (Spain). We performed statistical analyses on their anthropometric and socioeconomic data. High median levels of POPs were found in the overall sample, with differences among the countries. Organochlorine pesticide (OCP) and polychlorinated biphenyl (PCB) levels increased with age. People from low-income countries had significantly higher OCP levels and much lower PCB levels than those from high income countries. We found a significant association between the implementation of ICT and PCB contamination. Immigrants from the countries with a high volume of imports of second-hand electronic equipment had higher PCB levels. The economic development of Africa and the e-waste generation have directly affected the levels of POPs. The POP legacies of these African populations most likely are due to the inappropriate management of the POPs' residues. PMID- 25127445 TI - A nationwide survey and emission estimates of cyclic and linear siloxanes through sludge from wastewater treatment plants in Korea. AB - Siloxanes are widely used in various industrial applications as well as in personal care products. Despite their widespread use and potential toxic effects, few studies have reported on the occurrence of siloxanes in the environment. In this study, we determined the concentrations of 5 cyclic and 15 linear siloxanes in sludge collected from 40 representative wastewater treatment plants (WWTPs) in Korea. Total concentrations of 20 siloxanes (Sigmasiloxane) in sludge ranged from 0.05 to 142 (mean: 45.7) MUg/g dry weight, similar to the concentrations reported in European countries but higher than those reported in China. The concentrations of siloxanes in sludge from domestic WWTPs were significantly (p<0.01) higher than those from industrial WWTPs, indicating higher consumption of siloxanes in various personal care products (e.g. shampoos and conditioners). The major siloxane compounds found in sludge were decamethylcyclopentasilane (D5), docosamethyldecasiloxane (L10) and dodecamethylcyclohexasilane (D6), which collectively accounted for, on average, 62% of the Sigmasiloxane concentrations. Non-parametric multidimensional scaling ordination of the profiles of siloxanes indicated the existence of different usage patterns of siloxanes between industrial and household activities. Multiple linear regression analysis of siloxane concentrations and WWTP characteristics suggested that D5, D6 and linear siloxane concentrations in sludge were positively correlated with population served by a WWTP. Environmental emission fluxes of cyclic and linear siloxanes through sludge disposal in Korea were 14,800 and 18,500 kg/year, respectively. This is the first report describing occurrence and environmental emission of siloxanes through sludge in Korea. PMID- 25127447 TI - Solid mesostructured polymer-surfactant films at the air-liquid interface. AB - Pioneering work by Edler et al. has spawned a new sub-set of mesostructured materials. These are solid, self-supporting films comprising surfactant micelles encased within polymer hydrogel; composite polymer-surfactant films can be grown spontaneously at the air-liquid interface and have defined and controllable mesostructures. Addition of siliconalkoxide to polymer-surfactant mixtures allows for the growth of mesostructured hybrid polymer-surfactant silica films that retain film geometry after calcinations and exhibit superior mechanical properties to typically brittle inorganic films. Growing films at the air-liquid interface provides a rapid and simple means to prepare ordered solid inorganic films, and to date the only method for generating mesostructured films thick enough (up to several hundred microns) to be removed from the interface. Applications of these films could range from catalysis to encapsulation of hydrophobic species and drug delivery. Film properties and mesostructures are sensitive to surfactant structure, polymer properties and polymer-surfactant phase behaviour: herein it will be shown how film mesostructure can be tailored by directing these parameters, and some interesting analogies will be drawn with more familiar mesostructured silica materials. PMID- 25127446 TI - Investigation of organochlorine pesticides from the Indus Basin, Pakistan: sources, air-soil exchange fluxes and risk assessment. AB - Present study aimed to evaluate the contamination status of organochlorine pesticides (OCPs) and their associated potential for air-soil exchange and health risks from ecologically important sites of the Indus Basin, Pakistan. Among different OCPs investigated, SigmaDDTs and SigmaHCHs were more prevalent compounds in the agricultural soils and ambient air samples of the study area. The average concentrations for DDTs were found higher at downstream agricultural sites, particularly at Head Panjnad (Soil: 320 ng/g; Air: 743 pg/m(3)) and acting as an ultimate sink of SigmaOCP burden in soils. Spatial distribution patterns inferred ubiquitous distribution of SigmaDDTs in soils and air of the study area. Source diagnostic ratios demonstrated that studied OCPs either are illegally being used in agricultural practices or/and they are residues of past use in the environment. Fugacity fraction model revealed wide variations (ff=0.12-0.94) with 20% of OCPs above equilibrium range and net volatilization of alpha-endosulfan, beta-HCH and o,p'-DDD. Assessment of cancer risks for OCPs indicated a higher cancer risk (CR>1*10(-6)) for the residents of the Indus Basin. According to the available soil quality guidelines, DDTs and HCHs were above the permissible limits and pose a threat to natural habitat and biodiversity of the Indus Basin. PMID- 25127448 TI - Motor and memory function in rat models of cyanide toxicity and vascular occlusion induced ischemic injury. AB - Although oxidative stress is characteristic of global vascular occlusion and cyanide toxicity, the pattern of cerebral metabolism reconditioning and rate of progression or reversal of neural tissue damage differ for both forms of ischemia. Thus, it is important to compare cognitive and motor functions in both models of ischemia involving cyanide treatment (CN) and vascular occlusion (VO). Adult Wistar rats (N=30) were divided into three groups; VO (n=12), CN (n=12) and Control-CO (n=6). The CN was treated with 30mg/Kg of potassium cyanide (KCN); VO was subjected to global vascular occlusion-both for duration of 10 days. The control (CO) was fed on normal rat chow and water for the same duration. At day 10, the test and control groups (CN, VO and CO) were subjected to motor function tests (Table edge tests and Open Field Test) and memory function tests (Y-Maze and Novel object recognition) while the withdrawal groups CN-I and VO-I were subjected to the same set of tests at day 20 (the withdrawal phase). The results show that both cyanide toxicity and vascular occlusion caused a decline in motor and memory function when compared with the control. Also, the cyanide treatment produced a more rapid decline in these behavioral parameters when compared with the vascular occlusion during the treatment phase. After the withdrawal phase, cyanide treatment (CN-I) showed either an improvement or restoration of motor and memory function when compared to the CN and control. Withdrawal of vascular occlusion caused no improvement, and in some cases a decline in motor and memory function. In conclusion, cyanide toxicity caused a decline in motor and memory function after the treatment while vascular occlusion caused no significant decline in cognition and motor function at this time. After the withdrawal phase, the effect of cyanide toxicity was reduced and significant improvements were observed in the behavioral tests (motor and cognitive), while a decline in these functions were seen in the vascular occlusion group after this phase. PMID- 25127450 TI - Production of destruxins from Metarhizium spp. fungi in artificial medium and in endophytically colonized cowpea plants. AB - Destruxins (DTXs) are cyclic depsipeptides produced by many Metarhizium isolates that have long been assumed to contribute to virulence of these entomopathogenic fungi. We evaluated the virulence of 20 Metarhizium isolates against insect larvae and measured the concentration of DTXs A, B, and E produced by these same isolates in submerged (shaken) cultures. Eight of the isolates (ARSEF 324, 724, 760, 1448, 1882, 1883, 3479, and 3918) did not produce DTXs A, B, or E during the five days of submerged culture. DTXs were first detected in culture medium at 2-3 days in submerged culture. Galleria mellonella and Tenebrio molitor showed considerable variation in their susceptibility to the Metarhizium isolates. The concentration of DTXs produced in vitro did not correlate with percent or speed of insect kill. We established endophytic associations of M. robertsii and M. acridum isolates in Vigna unguiculata (cowpeas) and Cucumis sativus (cucumber) plants. DTXs were detected in cowpeas colonized by M. robertsii ARSEF 2575 12 days after fungal inoculation, but DTXs were not detected in cucumber. This is the first instance of DTXs detected in plants endophytically colonized by M. robertsii. This finding has implications for new approaches to fungus-based biological control of pest arthropods. PMID- 25127451 TI - Productivity change of surgeons in an academic year. AB - OBJECTIVE: The goal of this study was to calculate total factor productivity of surgeons in an academic year and to evaluate the effect of surgical trainees on their productivity. STUDY DESIGN: We analyzed all the surgical procedures performed from April 1 through September 30, 2013 in the Teikyo University Hospital. The nonradial and nonoriented Malmquist model under the variable returns-to-scale assumptions was employed. A decision-making unit is defined as a surgeon with the highest academic rank in the surgery. Inputs were defined as the number of physicians who assisted in surgery, and the time of surgical operation from skin incision to skin closure. The output was defined as the surgical fee for each surgery. April is the beginning month of a new academic year in Japan, and we divided the study period into April to June and July to September 2013. We computed each surgeon's Malmquist index, efficiency change, and technical change. RESULTS: We analyzed 2789 surgical procedures that were performed by 105 surgeons. The Malmquist index of all surgeons was significantly greater than 1 (p = 0.0033). The technical change was significantly greater than 1 (p < 0.0001). However, the efficiency change was not statistically significantly different from 1 (p = 0.1817). CONCLUSIONS: The surgeons are less productive in the beginning months of a new academic year. The main factor of this productivity loss is considered to be surgical training. PMID- 25127452 TI - Development of a web-based laparoscopic technical skills assessment and testing instrument: a pilot study. AB - OBJECTIVE: Current surgical training programs rely heavily on subjective assessments to measure operative proficiency, despite heavy emphasis on standardized testing as a means to rank scholastic ability. A compact laparoscopic simulator was developed with the intention to create a technical skill evaluation system that resembles standardized testing to provide the user with real-time percentile scores in a variety of skill metrics. The calculation of percentiles is only accurate if the pool of scores resembles a specific distribution (e.g., normal or log-normal distribution). We hypothesize that the grading measures provided by the simulator will follow normal or log-normal distributions. MATERIALS AND METHODS: A total of 29 surgical trainees with varying levels of laparoscopic experience were surveyed regarding their current training, proficiencies, and experience with the Fundamentals of Laparoscopic Surgery curriculum and then asked to perform a standard peg-transfer task 5 times. A proprietary device placed along the trocars of a laparoscopic box trainer was used to gather data that, when subjected to unique algorithms, gave real-time, web-based feedback to trainees on the following metrics: volume of instrument use, economy of movement, angular instrument path, instrument rotation, bimanual coordination, smoothness, time to task completion, and depth perception. Numerical data were plotted on a frequency histogram. Minitab software was used to identify if individual metrics fit a standard distribution curve. Analysis of variance was used to differentiate among 3 established physician skill levels, as a means of assessing construct validity. RESULTS: In the goodness-of-fit tests performed, angular path, depth perception, rotation, and smoothness were found to best fit a log-normal distribution (p > 0.1). Bimanual coordination was found to fit a normal distribution (p >= 0.067). However, both normal and log-normal distributions were rejected (p <= 0.01) for the metrics of time, volume, and economy of movement. After separating participants into 3 groups based on level of experience with the Fundamentals of Laparoscopic Surgery curriculum, analysis of variance showed significant differences among all group means across the 5 metrics (i.e., angular path, depth perception, rotation, smoothness, and bimanual coordination; p <= 0.023). CONCLUSION: A proprietary device provided quantitative assessment of laparoscopic skills, which can be used to differentiate among skill levels. Of the 8 tested metrics, 5 fit a normal or log-normal distribution, meaning the scores can statistically be ranked by percentile. Time, volume, and economy of movement did not fit desired distributions. The grading system proved to have construct validity, indicating it may be useful in the longitudinal assessment of laparoscopic skills of surgical trainees. PMID- 25127453 TI - Novel therapy for pyridoxine dependent epilepsy due to ALDH7A1 genetic defect: L arginine supplementation alternative to lysine-restricted diet. AB - BACKGROUND AND HYPOTHESIS: Pyridoxine dependent epilepsy (PDE) due to mutations in the ALDH7A1 gene (PDE-ALDH7A1) is caused by alpha-aminoadipic-semialdehyde dehydrogenase enzyme deficiency in the lysine pathway resulting in the accumulation of alpha-aminoadipic acid semialdehyde (alpha-AASA). Classical presentation is neonatal intractable seizures with a dramatic response to pyridoxine. Pyridoxine therapy does not prevent developmental delays in the majority of the patients. We hypothesized that L-arginine supplementation will decrease accumulation of alpha-AASA by competitive inhibition of lysine transport into the central nervous system and improve neurodevelopmental and neurocognitive functions in PDE-ALDH7A1. METHODS: A 12-year-old male with PDE-ALDH7A1 was treated with l-arginine supplementation as an innovative therapy. Treatment outcome was monitored by cerebral-spinal-fluid (CSF) alpha-AASA measurements at baseline, 6th and 12th months of therapy. Neuropsychological assessments were performed at baseline and 12th months of therapy. RESULTS: L-arginine therapy was well tolerated without side effects. CSF alpha-AASA was decreased 57% at 12th months of therapy. Neuropsychological assessments revealed improvements in general abilities index from 108 to 116 and improvements in verbal and motor functioning at 12th months of therapy. CONCLUSION: The short-term treatment outcome of this novel L-arginine supplementation therapy for PDE-ALDH7A1 was successful for biochemical and neurocognitive improvements. PMID- 25127454 TI - Moving to universal coverage? Trends in the burden of out-of-pocket payments for health care across social groups in India, 1999-2000 to 2011-12. AB - In the background of ongoing health sector reforms in India, the paper investigates the magnitude and trends in out-of-pocket and catastrophic payments for key population sub-groups. Data from three rounds of nationally representative consumer expenditure surveys (1999-2000, 2004-05 and 2011-12) were pooled to assess changes over time in a range of out-of-pocket -related outcome indicators for the poorest 20% households, scheduled caste and tribe households and Muslims households relative to their better-off/majority religion counterparts. Our results suggest that the poorest 20% of households experienced a decline in the proportion reporting any OOP for inpatient care relative to the top 20% and Muslim households saw an increase in the proportion reporting any inpatient OOP relative to non-Muslim households during 2000-2012. The change in the proportion of Muslim households or SC/ST households reporting any OOP for outpatient care was similar to that for their respective more advantaged counterparts; but the poorest 20% of households experienced a faster increase in the proportion reporting any OOP for outpatient care than their top 20% counterparts. SC/ST, Muslim and the poorest 20% of households experienced as faster increase in the share of outpatient OOP in total household spending relative to their advantaged counterparts. We conclude that the financial burden of out of pocket spending increased faster among the disadvantaged groups relative to their more advantaged counterparts. Although the poorest 20% saw a relative decline in OOP spending on inpatient care as a share of household spending, this is likely the result of foregoing inpatient care, than of accessing benefits from the recent expansion of cashless publicly financed insurance schemes for inpatient care. Our results highlight the need to explore the reasons underlying the lack of effectiveness of existing public health financing programs and public sector health services in reaching less-advantaged castes and religious minorities. PMID- 25127455 TI - Patterns of tree species diversity in relation to climatic factors on the Sierra Madre Occidental, Mexico. AB - Biological diversity can be defined as variability among living organisms from all sources, including terrestrial organisms, marine and other aquatic ecosystems, and the ecological complexes which they are part of. This includes diversity within species, between species, and of ecosystems. Numerous diversity indices combine richness and evenness in a single expression, and several climate based explanations have been proposed to explain broad-scale diversity patterns. However, climate-based water-energy dynamics appears to be an essential factor that determines patterns of diversity. The Mexican Sierra Madre Occidental occupies an area of about 29 million hectares and is located between the Neotropical and Holarctic ecozones. It shelters a high diversity of flora, including 24 different species of Pinus (ca. 22% on the whole), 54 species of Quercus (ca. 9-14%), 7 species of Arbutus (ca. 50%) and many other trees species. The objectives of this study were to model how tree species diversity is related to climatic and geographic factors and stand density and to test the Metabolic Theory, Productivity-Diversity Hypothesis, Physiological Tolerance Hypothesis, Mid-Domain Effect, and the Water-Energy Dynamic Theory on the Sierra Madre Occidental, Durango. The results supported the Productivity-Diversity Hypothesis, Physiological Tolerance Hypothesis and Water-Energy Dynamic Theory, but not the Mid-Domain Effect or Metabolic Theory. The annual aridity index was the variable most closely related to the diversity indices analyzed. Contemporary climate was found to have moderate to strong effects on the minimum, median and maximum tree species diversity. Because water-energy dynamics provided a satisfactory explanation for the patterns of minimum, median and maximum diversity, an understanding of this factor is critical to future biodiversity research. Quantile regression of the data showed that the three diversity parameters of tree species are generally higher in cold, humid temperate climates than in dry, hot climates. PMID- 25127457 TI - Cognitive dysfunction in Parkinson's disease related to the R1441G mutation in LRRK2. AB - OBJECTIVE: The neuropsychological characteristics of patients with Parkinson's Disease (PD) associated with R1441G mutation in the LRRK2 gene (R1441G-PD) are not well known. The aim of this study was to examine the cognitive status and mood of R1441G-PD patients. METHODS: Thirty patients with R1441G-PD were compared with thirty idiopathic PD (i-PD) patients who were matched by age, sex, education, disease onset age and duration, using a comprehensive battery of neuropsychological test, and considering the Movement Disorder Society (MDS) criteria for the diagnosis of Mild Cognitive Impairment (PD-MCI) and dementia (PD Dementia). RESULTS: The mean scores in the depression and anxiety scales were similar in the two groups. Depressive symptoms were detected in 31.8% of R1441G PD and 25% of i-PD patients and anxiety symptoms were evident in 4.5% and 15%, respectively, but the differences were not significant. The only neuropsychological test on which there was a significantly worse performance in the R1441G-PD group was the Boston naming test but the difference became not significant when Bonferroni's correction was applied. The prevalence of PD-MCI was 30% in both R1441G-PD and i-PD, with no differences in the number and type of domains altered given that executive function, memory and attention were mainly affected. PD-Dementia was diagnosed in 13.3% (n = 4) of R1441G-PD and 26.7% (n = 8) of i-PD patients (difference was not significant). CONCLUSION: In conclusion, significant differences were not detected between R1441G-PD and i-PD in cognitive, depression and anxiety scales, or PD-MCI and PD-Dementia prevalence, and the cognitive profile was identical in the two groups. PMID- 25127456 TI - Benign and malignant nodular thyroid disease in acromegaly. Is a routine thyroid ultrasound evaluation advisable? AB - Data on the prevalence of benign and malignant nodular thyroid disease in patients with acromegaly is a matter of debate. In the last decade an increasing incidence of thyroid cancer has been reported. The aim of this study was to evaluate the prevalence of goiter, thyroid nodules and thyroid cancer in a large series of patients with acromegaly with a cross-sectional study with a control group. Six Spanish university hospitals participated. One hundred and twenty three patients (50% men; mean age 59+/-13 years; disease duration 6.7+/-7.2 years) and 50 controls (51% males, mean age 58+/-15 years) were studied. All participants underwent thyroid ultrasound and fine needle aspiration. Cytological analysis was performed in suspicious nodules between 0.5 and 1.0 cm and in all nodules greater than 1.0 cm. Goiter was more frequently found in patients than in controls (24.9 vs. 8.3%, respectively; p<0.001). Nodular thyroid disease as well as nodules greater than 1 cm were also more prevalent in acromegalic patients (64.6%, vs. 28.6%, p<0.05 and 53.3 vs. 28.6%, respectively; p<0.05), and all underwent fine needle aspiration. Suspicious cytology was detected in 4 patients and in none of the controls. After thyroidectomy, papillary thyroid carcinoma was confirmed in two cases (3.3% of patients with thyroid nodules), representing 1.6% of the entire group of patients with acromegaly (2.4% including a case with previously diagnosed papillary thyroid carcinoma). These data indicated that thyroid nodular disease and cancer are increased in acromegaly, thus justifying its routine ultrasound screening. PMID- 25127458 TI - A new highly sensitive method to assess respiration rates and kinetics of natural planktonic communities by use of the switchable trace oxygen sensor and reduced oxygen concentrations. AB - Oxygen respiration rates in pelagic environments are often difficult to quantify as the resolutions of our methods for O2 concentration determination are marginal for observing significant decreases during bottle incubations of less than 24 hours. Here we present the assessment of a new highly sensitive method, that combine Switchable Trace Oxygen (STOX) sensors and all-glass bottle incubations, where the O2 concentration was artificially lowered. The detection limit of respiration rate by this method is inversely proportional to the O2 concentration, down to <2 nmol L(-1) h(-1) for water with an initial O2 concentration of 500 nmol L(-1). The method was tested in Danish coastal waters and in oceanic hypoxic waters. It proved to give precise measurements also with low oxygen consumption rates (~7 nmol L(-1) h(-1)), and to significantly decrease the time required for incubations (<=14 hours) compared to traditional methods. This method provides continuous real time measurements, allowing for a number of diverse possibilities, such as modeling the rate of oxygen decrease to obtain kinetic parameters. Our data revealed apparent half-saturation concentrations (Km values) one order of magnitude lower than previously reported for marine bacteria, varying between 66 and 234 nmol L(-1) O2. Km values vary between different microbial planktonic communities, but our data show that it is possible to measure reliable respiration rates at concentrations ~0.5-1 umol L(-1) O2 that are comparable to the ones measured at full air saturation. PMID- 25127459 TI - The fate of nitrate in intertidal permeable sediments. AB - Coastal zones act as a sink for riverine and atmospheric nitrogen inputs and thereby buffer the open ocean from the effects of anthropogenic activity. Recently, microbial activity in sandy permeable sediments has been identified as a dominant source of N-loss in coastal zones, namely through denitrification. Some of the highest coastal denitrification rates measured so far occur within the intertidal permeable sediments of the eutrophied Wadden Sea. Still, denitrification alone can often account for only half of the substantial nitrate (NO3-) consumption. Therefore, to investigate alternative NO3- sinks such as dissimilatory nitrate reduction to ammonium (DNRA), intracellular nitrate storage by eukaryotes and isotope equilibration effects we carried out 15NO3- amendment experiments. By considering all of these sinks in combination, we could quantify the fate of the 15NO3- added to the sediment. Denitrification was the dominant nitrate sink (50-75%), while DNRA, which recycles N to the environment accounted for 10-20% of NO3- consumption. Intriguingly, we also observed that between 20 and 40% of 15NO3- added to the incubations entered an intracellular pool of NO3- and was subsequently respired when nitrate became limiting. Eukaryotes were responsible for a large proportion of intracellular nitrate storage, and it could be shown through inhibition experiments that at least a third of the stored nitrate was subsequently also respired by eukaryotes. The environmental significance of the intracellular nitrate pool was confirmed by in situ measurements which revealed that intracellular storage can accumulate nitrate at concentrations six fold higher than the surrounding porewater. This intracellular pool is so far not considered when modeling N-loss from intertidal permeable sediments; however it can act as a reservoir for nitrate during low tide. Consequently, nitrate respiration supported by intracellular nitrate storage can add an additional 20% to previous nitrate reduction estimates in intertidal sediments, further increasing their contribution to N-loss. PMID- 25127461 TI - Novel N-biphenyl-2-ylmethyl 2-methoxyphenylpiperazinylalkanamides as 5-HT7R antagonists for the treatment of depression. AB - 5-HT7 receptor (5-HT7R) is a promising target for the treatment of depression and neuropathic pain. 5-HT7R antagonists exhibited antidepressant effects, while the agonists produced strong anti-hyperalgesic effects. In our efforts to discover selective 5-HT7R antagonists or agonists, N-biphenylylmethyl 2 methoxyphenylpiperazinylalkanamides 1 were designed, synthesized, and biologically evaluated against 5-HT7R. Among the synthesized compounds, N-2' chlorobiphenylylmethyl 2-methoxyphenylpiperazinylpentanamide 1-8 showed the best binding affinity with a Ki value of 8.69nM and it was verified as a novel antagonist according to functional assays. The compound 1-8 was very selective over 5-HT1DR, 5-HT2AR, 5-HT3R, 5-HT5AR and 5-HT6R and moderately selective over 5 HT1AR, 5-HT1BR and 5-HT2CR. The novel 5-HT7R antagonist 1-8 exhibited an antidepressant effect at a dose of 25mg/kg in the forced swimming test in mice and showed a U-shaped dose-response curve which typically appears in 5-HT7R antagonists such as SB-269970 and lurasidone. PMID- 25127462 TI - Synthesis and antifungal activity of substituted salicylaldehyde hydrazones, hydrazides and sulfohydrazides. AB - Efficient synthetic procedures for the preparation of acid hydrazines and hydrazides were developed by converting the corresponding carboxylic acid into the methyl ester catalyzed by Amberlyst-15, followed by a reaction with hydrazine monohydrate. Sulfohydrazides were prepared from the corresponding sulfonyl chlorides and hydrazine monohydrate. Both of these group of compounds were condensed with substituted salicylaldehydes using gradient concentration methods that generated a large library of hydrazone, hydrazide and sulfohydrazide analogs. Antifungal activity of the prepared analogs showed that salicylaldehyde hydrazones and hydrazides are potent inhibitors of fungal growth with little to no mammalian cell toxicity, making these analogs promising new targets for future therapeutic development. PMID- 25127463 TI - 2-Phenylaminonaphthoquinones and related compounds: synthesis, trypanocidal and cytotoxic activities. AB - A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the synthesized quinones were tested against cancer cells and normal fibroblasts, showing that certain chemical modifications on the naphthoquinone moiety induce and excellent increase the selectivity index of the cytotoxicity (4g and 10). The results presented here show that the anti-T. cruzi activity of 2 aminonaphthoquinones derivatives can be improved by the replacement of the benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed elements that should lead to the discovery of more selective cytotoxic and trypanocidal compounds. PMID- 25127464 TI - Design, synthesis, and in vitro evaluation of an activity-based protein profiling (ABPP) probe targeting agmatine deiminases. AB - Agmatine deiminases (AgDs) belong to a family of enzymes known as guanidinium group modifying enzymes (GMEs). Many pathogenic bacteria encode an AgD that participates in the catabolism of agmatine (decarboxylated arginine). This catabolism may confer a competitive survival advantage, by virtue of energy production and increased acid tolerance, making this sub-family of enzymes a potential therapeutic target that warrants further study. Herein we report the development of an activity-based protein profiling (ABPP) probe that selectively targets the AgD from Streptococcus mutans. Due to the selectivity and covalent nature of the modification, this probe could prove to be a valuable tool for the study of other AgD family members. PMID- 25127465 TI - Identification of novel inhibitors of phospho-MurNAc-pentapeptide translocase MraY from library screening: Isoquinoline alkaloid michellamine B and xanthene dye phloxine B. AB - The National Cancer Institute (NCI) Diversity Set was screened for potential inhibitors of phospho-MurNAc-pentapeptide translocase MraY from Escherichia coli using a primary fluorescence enhancement assay, followed by a secondary radiochemical assay. One new MraY inhibitor was identified from this screen, a naphthylisoquinoline alkaloid michellamine B, which inhibited E. coli MraY (IC50 456MUM) and Bacillus subtilis MraY (IC50 386MUM), and which showed antimicrobial activity against B. subtilis (MIC 16MUg/mL). Following an earlier report of halogenated fluoresceins identified from a combined MraY/MurG screen, three halogenated fluoresceins were tested as inhibitors of E. coli MraY and E. coli MurG, and phloxine B was identified as an inhibitor of E. coli MraY (IC50 32MUM). Molecular docking of inhibitor structures against the structure of Aquifex aeolicus MraY indicates that phloxine B appears to bind to the Mg(2+) cofactor in the enzyme active site, while michellamine B binds to a hydrophobic groove formed between transmembrane helices 5 and 9. PMID- 25127466 TI - Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands. AB - It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex combination of more than one drug. In this paper, we have designed three hybrid molecules combining WM5, a quinolone derivative we previously identified as HIV Tat-mediated transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR 355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to investigate whether it could be possible to obtain molecules acting on both transcription steps of the HIV replicative cycle. One among the three designed multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation from latently infected OM10.1 cells, the anti-RT properties shown by all of the synthesized compounds did not translate into an anti-HIV activity in acutely infected cells. Thus, we have herein produced the proof of concept that the design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are needed to obtain more potent derivatives. PMID- 25127467 TI - Sequence-specific DNA alkylation and transcriptional inhibition by long-chain hairpin pyrrole-imidazole polyamide-chlorambucil conjugates targeting CAG/CTG trinucleotide repeats. AB - Introducing novel building blocks to solid-phase peptide synthesis, we readily synthesized long-chain hairpin pyrrole-imidazole (PI) polyamide-chlorambucil conjugates 3 and 4 via the introduction of an amino group into a GABA (gamma turn) contained in 3, to target CAG/CTG repeat sequences, which are associated with various hereditary disorders. A high-resolution denaturing polyacrylamide sequencing gel revealed sequence-specific alkylation both strands at the N3 of adenines or guanines in CAG/CTG repeats by conjugates 3 and 4, with 11bp recognition. In vitro transcription assays using conjugate 4 revealed that specific alkylation inhibited the progression of RNA polymerase at the alkylating sites. Chiral substitution of the gamma-turn with an amino group resulted in higher binding affinity observed in SPR assays. These assays suggest that conjugates 4 with 11bp recognition has the potential to cause specific DNA damage and transcriptional inhibition at the alkylating sites. PMID- 25127468 TI - Ecological routes of avian influenza virus transmission to a common mesopredator: an experimental evaluation of alternatives. AB - BACKGROUND: Wild raccoons have been shown to be naturally exposed to avian influenza viruses (AIV). However, the mechanisms associated with these natural exposures are not well-understood. METHODOLOGY/PRINCIPAL FINDINGS: We experimentally tested three alternative routes (water, eggs, and scavenged waterfowl carcasses) of AIV transmission that may explain how raccoons in the wild are exposed to AIV. Raccoons were exposed to 1) water and 2) eggs spiked with an AIV (H4N6), as well as 3) mallard carcasses experimentally inoculated with the same virus. Three of four raccoons exposed to the high dose water treatment yielded apparent nasal shedding of >10(2.0) PCR EID50 equivalent/mL. Little to no shedding was observed from the fecal route. The only animals yielding evidence of serologic activity during the study period were three animals associated with the high dose water treatment. CONCLUSIONS/SIGNIFICANCE: Overall, our results indicate that virus-laden water could provide a natural exposure route of AIV for raccoons and possibly other mammals associated with aquatic environments. However, this association appears to be related to AIV concentration in the water, which would constitute an infective dose. In addition, strong evidence of infection was only detected in three of four animals exposed to a high dose (e.g., 10(5.0) EID50/mL) of AIV in water. As such, water borne transmission to raccoons may require repeated exposures to water with high concentrations of virus. PMID- 25127470 TI - Ultrasensitive electrochemical detection of microRNA with star trigon structure and endonuclease mediated signal amplification. AB - MicroRNAs play important roles in gene regulation. They can be used as effective biomarkers for diagnosis and prognosis of diseases like cancers. Due to their intrinsic properties of short length, low abundance and sequence homology among family members, it is difficult to realize sensitive and selective detection with economical use of time and cost. Herein, we report an ultrasensitive electrochemical method for microRNA analysis employing two oligonucleotides and one endonuclease. Generally, a glassy carbon electrode is first covered with gold nanoparticles (AuNPs) mediated by poly(diallyldimethylammonium chloride) (PDDA). Then, thiolated capture probe (CP) with methylene blue (MB) labeled at 5' end is modified on the pretreated electrode. Hybridization occurs among target microRNA, CP and auxiliary probe (AP), forming a star trigon structure on the electrode surface. Subsequently, endonuclease recognizes and cleaves CP on CP/AP duplex, releasing microRNA and AP back to the solution. The two regenerated elements can then form another star trigon with other CP molecules, initiating cycles of CP cleavage and MB departure. Significant decrease of electrochemical signals is thus observed, which can be used to reflect the concentration of microRNA. This proposed method has a linear response to microRNA in a wide range from 100 aM to 1 nM and the sensitivity of attomolar level can be achieved. Moreover, it has high selectivity against single-base mismatch sequences and can be used directly in serum samples. Therefore, this method shows great feasibility for the detection of microRNA and may have potential applications in cancer diagnosis and prognosis. PMID- 25127469 TI - Evaluation of the contribution of multiple DAMPs and DAMP receptors in cell death induced sterile inflammatory responses. AB - When cells die by necrosis in vivo they stimulate an inflammatory response. It is thought that this response is triggered when the injured cells expose proinflammatory molecules, collectively referred to as damage associated molecular patterns (DAMPs), which are recognized by cells or soluble molecules of the innate or adaptive immune system. Several putative DAMPs and/or their receptors have been identified, but whether and how much they participate in responses in vivo is incompletely understood, and they have not previously been compared side-by-side in the same models. This study focuses on evaluating the contribution of multiple mechanisms that have been proposed to or potentially could participate in cell death-induced inflammation: The third component of complement (C3), ATP (and its receptor P2X7), antibodies, the C-type lectin receptor Mincle (Clec4e), and protease-activated receptor 2 (PAR2). We investigate the role of these factors in cell death-induced inflammation to dead cells in the peritoneum and acetaminophen-induced liver damage. We find that mice deficient in antibody, C3 or PAR2 have impaired inflammatory responses to dying cells. In contrast there was no reduction in inflammation to cell death in the peritoneum or liver of mice that genetically lack Mincle, the P2X7 receptor or that were treated with apyrase to deplete ATP. These results indicate that antibody, complement and PAR2 contribute to cell death-induced inflammation but that Mincle and ATP- P2X7 receptor are not required for this response in at least 2 different in vivo models. PMID- 25127471 TI - Screen-printed microfluidic dielectrophoresis chip for cell separation. AB - Dielectrophoresis (DEP), the induced motion of polarizable particles in a non uniform electric field, has been proven as a perfect candidate to transport, accumulate, separate and characterize micro-/nano-scale bioparticles in microfluidic systems. However, conventional fabrication technologies are complex, time-consuming and relatively expensive, leading to low throughput of the DEP based systems. In this paper, we report a novel microfluidic alternating current DEP (AC-DEP) chip fabricated via inexpensive screen printing method. The innovation of our work consists in the extreme simplicity of the fabrication procedure, i.e., the main components, including electrodes and channels, were constructed by layer-by-layer screen printing process, which is especially suitable for high-throughput mass production. Carbon paste, instead of metals, was used to print interdigitated electrodes with semi-3D structure which not only reduces dramatically the chip cost but also increases particle trapping efficiency. To test the chip performance, yeast cells, as model cells, were trapped and separated from a mixed suspension with PS microspheres. Our results show that high capture rate and separation efficiency can be achieved under optimized conditions. PMID- 25127472 TI - A cost-effective Z-folding controlled liquid handling microfluidic paper analysis device for pathogen detection via ATP quantification. AB - A cost-effective microfluidic paper analysis device (MUPAD) was developed with a special Z-folding design for controlling the fluidic flowing and substrate transportation. This presented MUPAD can be easily fabricated through wax printing by using a solid ink printer which deposits wax onto the surface of a chromatographic paper, and then baked on a hotplate by penetrating the molten wax into the paper to create a hydrophobic barrier. After MUPAD fabrication, liquid control and substrate transportation can be easily carried out by twice folding the MUPAD following Z shape. The Z folding made two separated reagent holding zone connected while the detection reaction occurred with the connection. In this paper, a pathogens detection indicated by ATP quantification was took as a proof in-principle application of using this presented MUPAD, the limit of detection (LOD) was 1 MUM for ATP detection and 2.6*10(7) CFU/mL for Salmonella live cell detection, which showed a great potential for Point-of-Care Testing (POCT) applications. PMID- 25127473 TI - The peroxidase/catalase-like activities of MFe2O4 (M=Mg, Ni, Cu) MNPs and their application in colorimetric biosensing of glucose. AB - MFe2O4 (M=Mg, Ni, Cu) magnetic nanoparticles (MNPs) were found to have catalytic activities similar to those of biological enzymes such as catalase and peroxidase. These nanomaterials, as bifunctional catalase/peroxidases (KatGs), not only could catalyze H2O2 to produce hydroxyl radicals, which oxidized peroxidase substrate to produce color, but also could catalyze the decomposition reaction of H2O2 into water and oxygen directly in the same condition through the catalase-like activity. And it was also found that the amount of generated hydroxyl radicals and oxygen was related to the concentration of MFe2O4 (M=Mg, Ni, Cu) MNPs. The peroxidase-like catalytic behavior of MFe2O4 MNPs was analyzed in detail. Under the optimized conditions, NiFe2O4 MNPs were used as a colorimetric biosensor for the detection of 9.4*10(-7)-2.5*10(-5) mol L(-1) glucose with a limit of detection (LOD) of 4.5*10(-7) mol L(-1). The sensor was successfully applied to glucose detection in urine sample. PMID- 25127474 TI - Development of highly sensitive electrochemical genosensor based on multiwalled carbon nanotubes-chitosan-bismuth and lead sulfide nanoparticles for the detection of pathogenic Aeromonas. AB - In this paper, we reported the construction of new high sensitive electrochemical genosensor based on multiwalled carbon nanotubes-chitosan-bismuth complex (MWCNT Chi-Bi) and lead sulfide nanoparticles for the detection of pathogenic Aeromonas. Lead sulfide nanoparticles capped with 5'-(NH2) oligonucleotides thought amide bond was used as signalizing probe DNA (sz-DNA) and thiol-modified oligonucleotides sequence was used as fixing probe DNA (fDNA). The two probes hybridize with target Aeromonas DNA (tDNA) sequence (fDNA-tDNA-szDNA). The signal of hybridization is detected by differential pulse voltammetry (DPV) after electrodeposition of released lead nanoparticles (PbS) from sz-DNA on the surface of glass carbon electrode decorated with MWCNT-Chi-Bi, which improves the deposition and traducing electrical signal. The optimization of incubation time, hybridization temperature, deposition potential, deposition time and the specificity of the probes were investigated. Our results showed the highest sensibility to detect the target gene when compared with related biosensors and polymerase chain reaction (PCR). The detection limit for this biosensor was 1.0*10(-14) M. We could detect lower than 10(2) CFU mL(-1) of Aeromonas in spiked tap water. This method is rapid and sensitive for the detection of pathogenic bacteria and would become a potential application in biomedical diagnosis, food safety and environmental monitoring. PMID- 25127475 TI - Electrochemical biosensor for carbofuran pesticide based on esterases from Eupenicillium shearii FREI-39 endophytic fungus. AB - In this work, a biosensor was constructed by physical adsorption of the isolated endophytic fungus Eupenicillium shearii FREI-39 esterase on halloysite, using graphite powder, multi-walled carbon nanotubes and mineral oil for the determination of carbofuran pesticide by inhibition of the esterase using square wave voltammetry (SWV). Specific esterase activities were determined each 2 days over a period of 15 days of growth in four different inoculation media. The highest specific activity was found on 6th day, with 33.08 U on PDA broth. The best performance of the proposed biosensor was obtained using 0.5 U esterase activity. The carbofuran concentration response was linear in the range from 5.0 to 100.0 ug L(-1) (r=0.9986) with detection and quantification limits of 1.69 ug L(-1) and 5.13 ug L(-1), respectively. A recovery study of carbofuran in spiked water samples showed values ranging from 103.8+/-6.7% to 106.7+/-9.7%. The biosensor showed good repeatability and reproducibility and remained stable for a period of 20 weeks. The determination of carbofuran in spiked water samples using the proposed biosensor was satisfactory when compared to the chromatographic reference method. The results showed no significant difference at the 95% confidence level with t-test statistics. The application of enzymes from endophytic fungi in constructing biosensors broadens the biotechnological importance of these microorganisms. PMID- 25127476 TI - Associations between rice, noodle, and bread intake and sleep quality in Japanese men and women. AB - BACKGROUND: Previous studies have shown that a diet with a high-glycemic index is associated with good sleep quality. Therefore, we investigated the association of sleep quality with the intake of 3 common starchy foods with different glycemic indexes-rice, bread, and noodles-as well as the dietary glycemic index in a Japanese population. METHODS: The participants were 1,848 men and women between 20 and 60 years of age. Rice, bread, and noodle consumption was evaluated using a self-administered diet history questionnaire. Sleep quality was evaluated by using the Japanese version of the Pittsburgh Sleep Quality Index, and a global score >5.5 was considered to indicate poor sleep. RESULTS: Multivariate-adjusted odds ratios (95% confidence intervals) for poor sleep across the quintiles of rice consumption were 1.00 (reference), 0.68 (0.49-0.93), 0.61 (0.43-0.85), 0.59 (0.42-0.85), and 0.54 (0.37-0.81) (p for trend = 0.015); those for the quintiles of noodle consumption were 1.00 (reference), 1.25 (0.90-1.74), 1.05 (0.75-1.47), 1.31 (0.94-1.82), and 1.82 (1.31-2.51) (p for trend = 0.002). Bread intake was not associated with sleep quality. A higher dietary glycemic index was significantly associated with a lower risk of poor sleep (p for trend = 0.020). CONCLUSION: A high dietary glycemic index and high rice consumption are significantly associated with good sleep in Japanese men and women, whereas bread intake is not associated with sleep quality and noodle consumption is associated with poor sleep. The different associations of these starchy foods with sleep quality might be attributable to the different glycemic index of each food. PMID- 25127477 TI - Helium generated cold plasma finely regulates activation of human fibroblast-like primary cells. AB - Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS) in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR)-gamma, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine) cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-gamma anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and can be considered a valid therapeutic approach for liver and gut lesions. PMID- 25127479 TI - Buckley-James estimator of AFT models with auxiliary covariates. AB - In this paper we study the Buckley-James estimator of accelerated failure time models with auxiliary covariates. Instead of postulating distributional assumptions on the auxiliary covariates, we use a local polynomial approximation method to accommodate them into the Buckley-James estimating equations. The regression parameters are obtained iteratively by minimizing a consecutive distance of the estimates. Asymptotic properties of the proposed estimator are investigated. Simulation studies show that the efficiency gain of using auxiliary information is remarkable when compared to just using the validation sample. The method is applied to the PBC data from the Mayo Clinic trial in primary biliary cirrhosis as an illustration. PMID- 25127481 TI - Do diabetic kidneys deserve a lifestyle change? PMID- 25127478 TI - Disruption of axonal transport perturbs bone morphogenetic protein (BMP)- signaling and contributes to synaptic abnormalities in two neurodegenerative diseases. AB - Formation of new synapses or maintenance of existing synapses requires the delivery of synaptic components from the soma to the nerve termini via axonal transport. One pathway that is important in synapse formation, maintenance and function of the Drosophila neuromuscular junction (NMJ) is the bone morphogenetic protein (BMP)-signaling pathway. Here we show that perturbations in axonal transport directly disrupt BMP signaling, as measured by its downstream signal, phospho Mad (p-Mad). We found that components of the BMP pathway genetically interact with both kinesin-1 and dynein motor proteins. Thick vein (TKV) vesicle motility was also perturbed by reductions in kinesin-1 or dynein motors. Interestingly, dynein mutations severely disrupted p-Mad signaling while kinesin 1 mutants showed a mild reduction in p-Mad signal intensity. Similar to mutants in components of the BMP pathway, both kinesin-1 and dynein motor protein mutants also showed synaptic morphological defects. Strikingly TKV motility and p-Mad signaling were disrupted in larvae expressing two human disease proteins; expansions of glutamine repeats (polyQ77) and human amyloid precursor protein (APP) with a familial Alzheimer's disease (AD) mutation (APPswe). Consistent with axonal transport defects, larvae expressing these disease proteins showed accumulations of synaptic proteins along axons and synaptic abnormalities. Taken together our results suggest that similar to the NGF-TrkA signaling endosome, a BMP signaling endosome that directly interacts with molecular motors likely exist. Thus problems in axonal transport occurs early, perturbs BMP signaling, and likely contributes to the synaptic abnormalities observed in these two diseases. PMID- 25127480 TI - Developmental exposure of mice to dioxin promotes transgenerational testicular inflammation and an increased risk of preterm birth in unexposed mating partners. AB - TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Using a mouse model, we previously found that adult female mice exposed in utero to TCDD (F1 generation) as well as multiple subsequent generations (F2-F4) exhibited reduced fertility and an increased incidence of spontaneous preterm birth. Additional studies revealed that male F1 mice with a similar in utero/developmental TCDD exposure also exhibited diminished fertility and conferred an increased risk of preterm birth to their unexposed mating partners. Herein, we extend these previous observations, reporting that reduced fertility in male F1 mice is linked to testicular inflammation which coincides with apoptosis of developing spermatocytes, sub-fertility and an increased risk of preterm birth in their unexposed mating partners. Significantly, in the absence of additional toxicant exposure, testicular inflammation and reduced fertility persisted in F2 and F3 males and their control mating partners also frequently exhibited spontaneous preterm birth. Although a steady, global decline in male fertility has been noted over the last few decades, the reasons for these changes have not been firmly established. Likewise, the PTB rate in the U.S. and other countries has paralleled industrial development, suggesting a possible relationship between environmental toxicant exposure and adverse pregnancy outcomes. Most current clinical strategies to prevent preterm birth are focused solely on the mother and have yielded limited benefits. In contrast, our studies strongly suggest that the preconception testicular health of the father is a critical determinant of pregnancy outcomes in mice. Future clinical studies should examine the potential contribution of the male to gestation length in women and whether efforts to reduce the incidence of preterm birth should be initiated in both parents prior to pregnancy. PMID- 25127482 TI - Combining incretin-based drugs and RAAS inhibitors: more cons than pros? PMID- 25127484 TI - Jenny Graves: the free spirit of scientific enquiry. PMID- 25127485 TI - Selective deficit of spatial short-term memory: Role of storage and rehearsal mechanisms. AB - We report the neuropsychological and MRI investigation of a patient (GP) who developed a selective impairment of spatial short-term memory (STM) following damage to the dorso-mesial areas of the right frontal lobe. We assessed in this patient spatial STM with an experimental procedure that evaluated immediate and 5 20 s delayed recall of verbal, visual and spatial stimuli. The patient scored significantly worse than normal controls on tests that required delayed recall of spatial data. This could not be ascribed to a deficit of spatial episodic long term memory because amnesic patients performed normally on these tests. Conversely, the patient scored in the normal range on tests of immediate recall of verbal, visual and spatial data and tests of delayed recall of verbal and visual data. Comparison with a previously described patient who had a selective deficit in immediate spatial recall and an ischemic lesion that affected frontal and parietal dorso-mesial areas in the right hemisphere (Carlesimo GA, Perri R, Turriziani P, Tomaiuolo F, Caltagirone C. Remembering what but not where: independence of spatial and visual working memory in the human brain. Cortex. 2001 Sep; 37(4):519-34) suggests that the right parietal areas are involved in the short-term storage of spatial information and that the dorso-mesial regions of the right frontal underlie mechanisms for the delayed maintenance of the same data. PMID- 25127486 TI - Multiplexed gold nanorod array biochip for multi-sample analysis. AB - Optical transduction of biological bindings based on localized surface plasmon resonance (LSPR) of gold nanorods (GNRs) is attractive for label-free biosensing. The aspect ratio (AR) dependence of LSPR band maxima inherently provides an ideal multiplex mechanism. GNRs of selected sizes can be combined to ensure distinct plasmon peaks in absorption spectrum. Monitoring the spectral shift at the dedicated peaks allows for simultaneous detection of the specific analyte. Here, we first transformed the GNR's multiplexed biosensing capability to a robust chip based format. Specifically, nanorods of AR 2.6 and 4.5 were assembled onto thiol terminated substrates, followed by functionalization of respective antibodies to construct a GNR multiplex biochip. As a model system, concentrations of human IgG and rabbit IgG were simultaneously measured by correlating red-shifts at distinct resonance peaks caused by specific target binding. The calibration curves exhibited linear relationship between the spectral shift and analyte amount. The sensing performance in multi-analyte mode correlated nicely with those for single analyte detection with minimal cross-reactivity. Moreover, mixed GNRs can be deposited in controllable array pattern on the glass chip to analyze numerous samples at the same time. Each GNRs dot functioned independently as a multiplexed plamonic sensor. Coupled with microplate reader, this GNR nanoarray chip can potentially result in large scale assay of samples concurrently while for each sample, a multi-analyte detection simultaneously if desired. The concept shown in this work is simple and versatile that will definitely be a new paradigm in high throughput protein biochip development in the era of nano-biosensing. PMID- 25127483 TI - Effect of a long-term behavioural weight loss intervention on nephropathy in overweight or obese adults with type 2 diabetes: a secondary analysis of the Look AHEAD randomised clinical trial. AB - BACKGROUND: Long-term effects of behavioural weight loss interventions on diabetes complications are unknown. In a secondary analysis of the Look AHEAD (Action for Health in Diabetes) multicentre randomised clinical trial, we assessed whether an intensive lifestyle intervention (ILI) affects the development of nephropathy in people with type 2 diabetes. METHODS: Overweight or obese people aged 45-76 years with type 2 diabetes were randomly assigned (1:1) to ILI or to a diabetes support and education (DSE) group by a central web-based data management system, stratified by clinical centre and blocked with random block sizes. The ILI was designed to achieve and maintain weight loss through reduced caloric consumption and increased physical activity. The interventions were terminated early because of absence of effect on the primary outcome of cardiovascular disease events in the main Look AHEAD trial. Albuminuria and estimated glomerular filtration rate were prespecified as two of many other outcomes and were assessed from baseline until the interventions ended. They were combined post hoc to define the main outcome for this report, very-high-risk chronic kidney disease (CKD), based on the 2013 Kidney Disease Improving Global Outcomes (KDIGO) classification. Outcomes assessors and laboratory staff were masked to treatment, but participants and interventionists were not masked. Time to-event data were analysed by intention to treat by the Kaplan-Meier method and proportional hazards models. The Look AHEAD trial is registered with ClinicalTrials.gov, NCT00017953. FINDINGS: Of the 5145 participants randomly assigned in the Look AHEAD trial (2570 to ILI and 2575 to DSE), analyses for very high-risk CKD were done in 2423 (94%) of patients in the ILI group and 2408 (94%) of those in the DSE group. After a median of 8.0 years (IQR 7.9-9.9) of follow up, the incidence of very-high-risk CKD was lower in the ILI group than in the DSE group, with incidence rates of 0.91 cases per 100 person-years in the DSE group and 0.63 per 100 person-years in the ILI group (difference 0.27 cases per 100 person-years, hazard ratio 0.69, 95% CI 0.55-0.87; p=0.0016). This effect was partly attributable to reductions in bodyweight, HbA1c, and systolic blood pressure. There were no safety concerns regarding kidney-related adverse events. INTERPRETATION: Weight loss should be considered as an adjunct to medical treatments to prevent or delay progression of CKD in overweight or obese people with type 2 diabetes. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases. PMID- 25127487 TI - Multi-level kinetic model explaining diverse roles of isozymes in prokaryotes. AB - Current standard methods for kinetic and genomic modeling cannot provide deep insight into metabolic regulation. Here, we developed and evaluated a multi-scale kinetic modeling approach applicable to any prokaryote. Specifically, we highlight the primary metabolism of the cyanobacterium Synechococcus elongatus PCC 7942. The model bridges metabolic data sets from cells grown at different CO2 conditions by integrating transcriptomic data and isozymes. Identification of the regulatory roles of isozymes allowed the calculation and explanation of the absolute metabolic concentration of 3-phosphoglycerate. To demonstrate that this method can characterize any isozyme, we determined the function of two glycolytic glyceraldehyde-3-phosphate dehydrogenases: one co-regulates high concentrations of the 3-phosphoglycerate, the other shifts the bifurcation point in hexose regulation, and both improve biomass production. Moreover, the regulatory roles of multiple phosphoglycolate phosphatases were defined for varying (non-steady) CO2 conditions, suggesting their protective role against toxic photorespiratory intermediates. PMID- 25127488 TI - Design changes improve contact patterns and articular surface damage in total knee arthroplasty. AB - BACKGROUND: The Optetrak PS (Exactech, Inc., Gainesville, FL) has been a well functioning posterior stabilized knee replacement since its introduction in 1995. In 2009, the Optetrak Logic incorporated modifications to the anterior face of the tibial post and the corresponding anterior articulating surface of the femoral component to reduce edge loading on the polyethylene post. In this study, we provide the rationale for the design change and compare the damage on retrieved tibial components of both designs to demonstrate the effectiveness of the design modifications in decreasing post damage. METHODS: We integrated retrieval findings of tibial post damage with finite element analysis to redesign the anterior tibial post-femoral box articulation. We then used subsequent retrieval analysis on a 3:1 matched sample of 60 PS and 20 Logic inserts to examine the impact of the design change on polyethylene damage. RESULTS: Polyethylene stresses were markedly reduced when rounded contact geometries were incorporated. The comparison of the new and old designs using retrieval analysis demonstrated that the redesign led to reduction in surface damage and deformation on the tibial post. CONCLUSIONS: This study shows the use of a design cycle by which a problem is identified through retrieval analysis, analytical tools are used to suggest design solutions, and then retrieval analysis is applied again on the new design to confirm improved performance. CLINICAL RELEVANCE: Anterior post damage has been markedly reduced through the introduction of design changes to the post-box geometry. PMID- 25127489 TI - N-acetyl-4-aminophenol (paracetamol) in urine samples of 6-11-year-old Danish school children and their mothers. AB - Recent studies indicate an association between the use of paracetamol during pregnancy and reproductive disorders in male offspring. Furthermore, N-acetyl-4 aminophenol (NAAP, paracetamol) has been shown to be ubiquitously excreted in urine samples of the general population. To investigate the internal body burden of the Danish population to NAAP for the first time, 288 morning urine samples from 6- to 11-year-old Danish school children and their mothers were analyzed for NAAP. NAAP was measurable in all mothers and all of the children except for one child. Results showed that there is a ubiquitous body burden of NAAP in Danish mothers and children even when paracetamol analgesics have not been used recently. Hence, several unknown sources of NAAP/paracetamol exposure have to exist. We found an association in NAAP excretion between the mothers and their children which could indicate common lifestyle related exposure (e.g. via food or indoor air sources). However, we did not detect any association between lifestyle data from questionnaires and levels of NAAP excretion in this study. The knowledge about possible sources of exposure leading to this omnipresent paracetamol excretion is limited and further investigation is wanted. PMID- 25127491 TI - Analysis of muscle activation patterns during transitions into and out of high knee flexion postures. AB - Increased risk of medial tibiofemoral osteoarthritis (OA) is linked to occupations that require frequent transitions into and out of postures which require high knee flexion (>90 degrees ). Muscle forces are major contributors to joint loading, and an association between compressive forces due to muscle activations and the degeneration of joint cartilage has been suggested. The purpose of this study was to evaluate muscle activation patterns of muscles crossing the knee during transitions into and out of full-flexion kneeling and squatting, sitting in a low chair, and gait. Both net and co-activation were greater when transitioning out of high flexion postures, with maximum activation occurring at knee angles greater than 100 degrees . Compared to gait, co activation levels during high flexion transitions were up to approximately 3 times greater. Co-activation was significantly greater in the lateral muscle group compared to the medial group during transitions into and out of high flexion postures. These results suggest that compression due to activation of the medial musculature of the knee may not be the link between high knee flexion postures and increased medial knee OA observed in occupational settings. Further research on a larger subject group and workers with varying degrees of knee OA is necessary. PMID- 25127490 TI - PCBs, PCDD/Fs, and PBDEs in blood samples of a rural population in South Germany. AB - The body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like (dl-PCBs) and non-dioxin-like (ndl-PCBs) polychlorinated biphenyls, and polybrominated diphenyl ethers (PBDEs) was determined in blood samples from 70 subjects between 4 and 76 years old. The participants of the study were recruited in the neighborhood of a reclamation plant located in a rural area in Southern Germany. The median concentrations (95th percentiles in parentheses), expressed as WHO2005-TEQ (toxic equivalents), for PCDD/Fs and dl-PCBs were 4.5 (17.9)pgg(-1) l.w. and 2.6 (13.2)pgg(-1) l.w., respectively. The dl-PCBs contributed 40% of the total TEQ (median values), and the most abundant congener was PCB 156. Combined, the sum of the 6 non-dioxin-like PCBs had a median of 0.773MUgL(-1) and a 95th percentile of 4.895MUgL(-1). For the six tetra to hepta PBDE congeners, the median was 1.8ngg(-1) l.w. (95th percentile: 16.2ngg(-1) l.w.). None of our study subjects had a body burden that exceeded the biomonitoring equivalents for dioxins or PBDE congener 99 or the human biomonitoring values for ndl-PCBs. Likewise the study group did not exceed German reference values or values obtained in similar investigations. Overall, our study did not exhibit elevated internal exposures. The results also hint further decreasing tendencies for PCDD/Fs, PCBs, and PBDEs in Germany and demonstrates that people in the vicinity of a reclamation plant with no indication of an environmental contamination did not exhibit elevated internal exposures. PMID- 25127492 TI - Altered corticomuscular coherence elicited by paced isotonic contractions in individuals with cerebral palsy: a case-control study. AB - The purpose of the study was to analyze corticomuscular coherence during planning and execution of simple hand movements in individuals with cerebral palsy (CP) and healthy controls (HC). Fourteen individuals with CP and 15 HC performed voluntary paced movements (opening and closing the fist) in response to a warning signal. Simultaneous scalp EEG and surface EMG of extensor carpi radialis brevis were recorded during 15 isotonic contractions. Time-frequency corticomuscular coherence (EMG-C3/C4) before and during muscular contraction, as well as EMG intensity, onset latency and duration were analyzed. Although EMG intensity was similar in both groups, individuals with CP exhibited longer onset latency and increased duration of the muscular contraction than HC. CP also showed higher corticomuscular coherence in beta EEG band during both planning and execution of muscular contraction, as well as lower corticomuscular coherence in gamma EEG band at the beginning of the contraction as compared with HC. In conclusion, our results suggest that individuals with CP are characterized by an altered functional coupling between primary motor cortex and effector muscles during planning and execution of isotonic contractions. In addition, the usefulness of corticomuscular coherence as a research tool for exploring deficits in motor central processing in persons with early brain damage is discussed. PMID- 25127493 TI - Reliability of telemetric electromyography and near-infrared spectroscopy during high-intensity resistance exercise. AB - This study quantified the inter- and intra-test reliability of telemetric surface electromyography (EMG) and near infrared spectroscopy (NIRS) during resistance exercise. Twelve well-trained young men performed high-intensity back squat exercise (12 sets at 70-90% 1-repetition maximum) on two occasions, during which EMG and NIRS continuously monitored muscle activation and oxygenation of the thigh muscles. Intra-test reliability for EMG and NIRS variables was generally higher than inter-test reliability. EMG median frequency variables were generally more reliable than amplitude-based variables. The reliability of EMG measures was not related to the intensity or number of repetitions performed during the set. No notable differences were evident in the reliability of EMG between different agonist muscles. NIRS-derived measures of oxyhaemoglobin, deoxyhaemoglobin and tissue saturation index were generally more reliable during single-repetition sets than multiple-repetition sets at the same intensity. Tissue saturation index was the most reliable NIRS variable. Although the reliability of the EMG and NIRS measures varied across the exercise protocol, the precise causes of this variability are not yet understood. However, it is likely that biological variation during multi-joint isotonic resistance exercise may account for some of the variation in the observed results. PMID- 25127494 TI - Pathophysiology of the constant burning, tingling element of neuropathic pain: a new hypothesis. AB - Neuropathic pain (NPP) presents itself with at least one of the following elements: constant, intermittent and evoked pain. The pathophysiology of NPP is still controversial, in especial of its constant element, the focus of this study. Many hypotheses have been proposed in an attempt to explain it, but none of them seems to account for the various aspects of the constant element of NPP. Under the phylogenetic perspective, it is postulated, the pain may be classified into two categories: paleopain, present in inferior animals, poorly localized, transmitted by the medial pain system pathways, and neopain, conducted by the lateral pain system pathways, very well localized, described in terms suggestive of tissue damage and present in superior animals. We believe that, in humans, under physiological circumstances, the expression of the paleopain was completely abolished. It is proposed that it is due to the tonic inhibition of the medial thalamus by the ventral posterior (VP) nucleus of the thalamus, via a circuit that the authors described and named prosencephalomesencephalic modulatory circuit (PMMC). Two pathways are suggested as activators of the PMMC: the neospinothalamic/neotrigeminothalamic and ventral spinothalamic tracts. The interruption of this circuit or of its activators, at any point, would lead to the release of the medial thalamus from the inhibitory influences of VP, allowing the manifestation of the paleopain. It is postulated that the constant burning, tingling element of NPP is nothing more than the clinical expression of the paleopain. Evidence to support this hypothesis is provided. As a direct consequence of the presented hypothesis, the substantia nigra pars reticulata is proposed as a new target of deep brain stimulation for the treatment of the constant burning, tingling element of NPP. PMID- 25127495 TI - Aristotle got it right again! PMID- 25127497 TI - Persistent organic pollutants in liver of Brazilian sharpnose shark (Rhizoprionodon lalandii) from southeastern coast of Brazil. AB - In the present study, persistent organic pollutants (POPs) were determined in 14 livers from specimens of the Brazilian sharpnose shark (Rhizoprionodon lalandii), which is an important economic resource for small-scale fisheries on the southeastern coast of Brazil. The following concentrations (lipid weight) of POPs were found: ?PCBs: 1019+/-267 ng g(-1); ?DDTs: 111+/-40 ng g(-1) and ?PBDEs: 10.4+/-4.78. PCB 153 made the greatest contribution to ?PCB (21.4%), followed by PCB 138 (14.6%) and PCB 180 (9.94%). Among chlorinated pesticides, only the p,p' DDE and p,p'-DDD isomers had concentrations above the detection limit. Moreover, levels above the detection limit were found only for PBDE congeners 47 and 100 (BDEs 47>99). On average, BDE 47 accounted for 88% of the total PBDE load. The feeding habits of the Brazilian sharpnose shark close to the Brazilian coastline are likely the most important difference regarding the accumulation of POPs in comparison to oceanic species that feed in deeper waters. Thus, this species may be used to evaluate the pollution of coastal areas as well as human exposure to contaminants, as the Brazilian sharpnose shark is a frequently used for human consumption. Further studies in other areas of Brazil and involving other species are needed to clarify the mechanisms and potential impact of POPs, which can affect the biology of different organisms and cause population declines. PMID- 25127498 TI - Steroid markers to assess sewage and other sources of organic contaminants in surface sediments of Cienfuegos Bay, Cuba. AB - Analyses of faecal steroids in coastal sediments from Cienfuegos Bay Cuba indicate chronic sewage contamination at the main outfalls from the city, where concentrations of coprostanol up to 5400ngg(-)(1) (dry wt) were measured. In contrast, steroid concentrations and compositions from sites from the south part of the Bay are characteristic of uncontaminated sewage environments. The levels of coprostanol in the Cienfuegos sediments compares to the lower to mid-range of concentrations reported for coastal sediments on a world-wide basis, with sedimentary levels markedly below those previously reported for heavily impacted sites. This study delivers baseline data for further investigation of the effectiveness of the proposed sewerage plan promoted by the GEF project in Cienfuegos. Investigations on the correlations between faecal steroids and other organic contaminants confirmed that the major source of petroleum hydrocarbons within the bay was associated with the sewage effluents from the Cienfuegos city. PMID- 25127499 TI - Response of multi-metric indices to anthropogenic pressures in distinct marine habitats: the need for recalibration to allow wider applicability. AB - Sustainable exploitation of coastal ecosystems is facilitated by tools which allow reliable assessment of their response to anthropogenic pressures. The Infaunal Quality Index (IQI) and Multivariate-AMBI (M-AMBI) were developed to classify the ecological status (ES) of benthos for the Water Framework Directive (WFD). The indices respond reliably to the impacts of organic enrichment in muddy sand habitats, but their applicability across a range of pressures and habitats is less well understood. The ability of the indices to predict changes in response to pressures in three distinct habitats, intertidal muddy sand, maerl and inshore gravel, was tested using pre-existing datasets. Both responded following the same patterns of variation as previously reported. The IQI was more conservative when responding to environmental conditions so may have greater predictive value in dynamic habitats to provide an early-warning system to managers'. Re-calibration of reference conditions is necessary to reliably reflect ES in different habitats. PMID- 25127496 TI - Mitochondria, energetics, epigenetics, and cellular responses to stress. AB - BACKGROUND: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria-nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. OBJECTIVES: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. METHODS: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25-26 March 2013. Here, we summarize key points and ideas emerging from this meeting. DISCUSSION: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. CONCLUSIONS: Understanding mitochondria-cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to environmental stressors. PMID- 25127500 TI - Changes in the concentration and relative abundance of alkanes and PAHs from the Deepwater Horizon oiling of coastal marshes. AB - We determined changes of 28 alkanes and 43 different PAHs in 418 wetland soil samples collected on ten sampling trips to three Louisiana estuaries before and after they were oiled from the 2010 Deepwater Horizon disaster. There was a significant decline in 22 of the 28 alkane analytes (0.42% day(-1)), no change in 6, over 2.5 years. The concentration of five aromatic petroleum hydrocarbons (PAHs) increased (range 0.25-0.70% day(-1)), whereas the total PAH pool did not change. Of these five, naphthalene and C-1-naphthalenes are suggested to be of higher toxicity than the other three because of their relatively higher volatility or solubility. The relative proportions of alkane analytes, but not PAHs, does not yet resemble that in the pre-oiled marshes after 3 years, The trajectories of nine indicators for degradation/weathering were either inconclusive or misleading (alkanes) or confirmed the relatively meager degradation of PAHs. PMID- 25127501 TI - Floating debris in the Mediterranean Sea. AB - Results from the first large-scale survey of floating natural (NMD) and anthropogenic (AMD) debris (>2 cm) in the central and western part of the Mediterranean Sea are reported. Floating debris was found throughout the entire study area with densities ranging from 0 to 194.6 items/km(2) and mean abundances of 24.9 AMD items/km(2) and 6.9 NMD items/km(2) across all surveyed locations. On the whole, 78% of all sighted objects were of anthropogenic origin, 95.6% of which were petrochemical derivatives (i.e. plastic and styrofoam). Maximum AMD densities (>52 items/km(2)) were found in the Adriatic Sea and in the Algerian basin, while the lowest densities (<6.3 items/km(2)) were observed in the Central Tyrrhenian and in the Sicilian Sea. All the other areas had mean densities ranging from 10.9 to 30.7 items/km(2). According to our calculations, more than 62 million macro-litter items are currently floating on the surface of the whole Mediterranean basin. PMID- 25127502 TI - Mediterranean diet and risk of frailty in community-dwelling older adults. AB - BACKGROUND AND OBJECTIVE: Low intake of certain micronutrients and protein has been associated with higher risk of frailty. However, very few studies have assessed the effect of global dietary patterns on frailty. This study examined the association between adherence to the Mediterranean diet (MD) and the risk of frailty in older adults. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study with 1815 community-dwelling individuals aged >=60 years recruited in 2008 2010 in Spain. MEASUREMENTS: At baseline, the degree of MD adherence was measured with the Mediterranean Diet Adherence Screener (MEDAS) score and the Mediterranean Diet Score, also known as the Trichopoulou index. In 2012, individuals were reassessed to detect incident frailty, defined as having at least 3 of the following criteria: exhaustion, muscle weakness, low physical activity, slow walking speed, and weight loss. The study associations were summarized with odds ratios (OR) and their 95% confidence interval (CI) obtained from logistic regression, with adjustment for the main confounders. RESULTS: Over a mean follow-up of 3.5 years, 137 persons with incident frailty were identified. Compared with individuals in the lowest tertile of the MEDAS score (lowest MD adherence), the OR (95% CI) of frailty was 0.85 (0.54-1.36) in those in the second tertile, and 0.65 (0.40-1.04; P for trend = .07) in the third tertile. Corresponding figures for the Mediterranean Diet Score were 0.59 (0.37-0.95) and 0.48 (0.30-0.77; P for trend = .002). Being in the highest tertile of MEDAS was associated with reduced risk of slow walking (OR 0.53; 95% CI 0.35-0.79) and of weight loss (OR 0.53; 95% CI 0.36-0.80). Lastly, the risk of frailty was inversely associated with consumption of fish (OR 0.66; 95% CI 0.45-0.97) and fruit (OR 0.59; 95% CI 0.39-0.91). CONCLUSIONS: Among community-dwelling older adults, an increasing adherence to the MD was associated with decreasing risk of frailty. PMID- 25127503 TI - A developmental screening tool for toddlers with multiple domains based on Rasch analysis. AB - BACKGROUND/PURPOSE: Using multidomain developmental screening tools is a feasible method for pediatric health care professionals to identify children at risk of developmental problems in multiple domains simultaneously. The purpose of this study was to develop a Rasch-based tool for Multidimensional Screening in Child Development (MuSiC) for children aged 0-3 years. METHODS: The MuSic was developed by constructing items bank based on three commonly used screening tools, validating with developmental status (at risk for delay or not) on five developmental domains. Parents of a convenient sample of 632 children (aged 3 35.5 months) with and without developmental delays responded to items from the three screening tools funded by health authorities in Taiwan. Item bank was determined by item fit of Rasch analysis for each of the five developmental domains (cognitive skills, language skills, gross motor skills, fine motor skills, and socioadaptive skills). Children's performance scores in logits derived in Rasch analysis were validated with developmental status for each domain using the area under receiver operating characteristic curves. RESULTS: MuSiC, a 75-item developmental screening tool for five domains, was derived. The diagnostic validity of all five domains was acceptable for all stages of development, except for the infant stage (<=11 months and 15 days). CONCLUSION: MuSiC can be applied simultaneously to well-child care visits as a universal screening tool for children aged 1-3 years on multiple domains. Items with sound validity for infants need to be further developed. PMID- 25127504 TI - Impact of guideline changes on use or omission of radiation in the elderly with early breast cancer: practice patterns at National Comprehensive Cancer Network institutions. AB - BACKGROUND: Breast radiation therapy (RT) is a care standard after breast conservation surgery that improves local control and survival in women. In 2004, a phase III trial demonstrated radiation after breast-conservation surgery provided no survival and limited local control benefit to women aged 70 years and older with stage I, estrogen receptor-positive cancers who receive endocrine therapy. This led to breast-conservation surgery and endocrine therapy alone being incorporated as a category I option in the National Comprehensive Cancer Network (NCCN) Guidelines for older women in 2004. We examined factors associated with change in radiation use in elderly patients at 13 NCCN centers. STUDY DESIGN: We identified women treated at NCCN centers meeting age and stage criteria during 2000 to 2009. Factors considered a priori potentially associated with RT use were evaluated in univariate and multivariable models, including year of diagnosis, tumor and patient characteristics, axillary surgery, and treating institution. Date of diagnosis was classified as 2000 to 2004 vs 2005 to 2009, reflecting when guidelines changed. RESULTS: Among 1,292 eligible cases, 78% received RT. In multivariable analysis, diagnosis after 2004 (p = 0.0003), older age (p < 0.0001), higher comorbidity score (p = 0.0006), smaller tumors (p = 0.0146), and omission of axillary surgery (p < 0.0001) predicted RT omission. Ninety-four percent of women aged 70 to 74 years received RT in 2000, compared with 88% in 2009. For the same times and age 80 years and older, RT use was 80% vs 41%. Finally, RT use was associated with treating institution (p < 0.0001). CONCLUSIONS: After guideline changes for RT use in older women, NCCN centers demonstrated wide variation in implementing change. This suggests other factors are also influencing guideline uptake. PMID- 25127505 TI - Modified rendezvous biliary procedure involving the hepatobiliary surgeon, endoscopist, and interventional radiologist: a novel solution for complex bile duct injuries. PMID- 25127506 TI - Reoperative complications after primary orthotopic liver transplantation: a contemporary single-center experience in the post-model for end-stage liver disease era. AB - BACKGROUND: Data on complications requiring reoperation after orthotopic liver transplantation (OLT) are limited. We sought to describe the spectrum of reoperative complications after OLT, evaluate the associations with graft and patient survival, and identify predictors of need for reoperation. STUDY DESIGN: We retrospectively studied adult patients who underwent primary OLT at our institution from February 2002 to July 2012. The primary outcomes included occurrence of a reoperative complication. Secondary outcomes were graft and patient survival. Multivariable logistic regression analysis was used to model the associations of recipient, donor, and operative variables with reoperation. RESULTS: Of 1,620 patients, 470 (29%) had complications requiring reoperation. The most common reoperative complication was bleeding (17.3%). Compared with patients not requiring reoperation, patients with reoperative complications had greater Model for End-Stage Liver Disease scores and need for pretransplantation hospitalization, mechanical ventilation, vasopressors, and renal replacement therapy; considerably longer cold and warm ischemia times and greater intraoperative blood transfusion requirements; and substantially worse 1-, 3-, and 5-year graft and patient survival rates. In multivariable analysis, predictors of reoperative complications included intraoperative transfusion of packed RBCs (odds ratio [OR] = 2.21; 95% CI, 1.91-2.56), donor length of hospitalization >8 days (OR = 1.87; 95% CI, 1.28-2.73), recipient pretransplantation mechanical ventilation (OR = 1.65; 95% CI, 1.21-2.24), cold ischemia time >9 hours (OR = 1.63; 95% CI, 1.23-2.17), warm ischemia time >55 minutes (OR = 1.58; 95% CI, 1.02-2.44), earlier major abdominal surgery (OR = 1.41; 95% CI, 1.03-1.92), and elevated donor serum sodium (OR = 1.17; 95% CI, 1.03-1.31). CONCLUSIONS: Patients who require reoperation for complications after OLT have high pretransplantation acuity and inferior post-transplantation survival. We identified factors associated with reoperative complications to guide perioperative donor-recipient matching and improve outcomes. PMID- 25127507 TI - Median arcuate ligament release. PMID- 25127508 TI - Practical management of postoperative atrial fibrillation after noncardiac surgery. PMID- 25127509 TI - Automated quantitative analysis of tissue microarray of 443 patients with colorectal adenocarcinoma: low expression of Bcl-2 predicts poor survival. AB - BACKGROUND: Bcl-2 has been implicated in the development and progression of a number of cancers including colorectal cancer. Reports of Bcl-2 expression in colorectal cancer and patient outcomes have been inconsistent due to small cohorts and semi-quantitative grading methods. STUDY DESIGN: We used a high throughput tissue microarray system (automated quantitative analysis [AQUA]), analyzing colorectal adenocarcinoma samples from 443 patients resected during the period of 1967 to 1986. This system uses fully quantitative, automated fluorescent microscopy to accurately assess Bcl-2 expression in colorectal cancer samples. Clinicopathologic variables were collected prospectively and were assessed using log-rank tests and Cox proportional hazards models. RESULTS: At a median follow-up of 54 months, the 5- and 10-year disease-specific survivals for all patients were 59.2% and 52.1%, respectively. Loss of Bcl-2 expression was seen in 70.4% of tumors and was associated with a decreased 5-year disease specific survival (55.8% vs 75.6%, p = 0.001 and relative risk [RR] 1.8) and decreased 5-year overall survival (45.8% vs 56.5%, p = 0.046 and RR 1.2). On univariate analysis, T stage, N stage, and loss of Bcl-2 expression predicted poor disease-specific survival. On multivariate analysis, Bcl-2 expression was an independent prognostic factor for disease-specific survival (p = 0.034). CONCLUSIONS: Our results indicate that loss of Bcl-2 expression in colorectal cancer is associated with decreased disease-specific and overall survival. This finding may help identify a subset of patients with a more aggressive phenotype and guide adjuvant chemotherapy choices. PMID- 25127510 TI - Isolated free fluid on abdominal computed tomography in blunt trauma: watch and wait or operate? AB - BACKGROUND: Isolated free fluid (FF) on abdominal CT in stable blunt trauma patients can indicate the presence of hollow viscus injury. No criteria exist to differentiate treatment by operative exploration vs observation. The goals of this study were to determine the incidence of isolated FF and to identify factors that discriminate between patients who should undergo operative exploration vs observation. STUDY DESIGN: A review of blunt trauma patients at a Level I trauma center from July 2009 to March 2012 was performed. Patients with a CT showing isolated FF after blunt trauma were included. Data collected included demographics, injury severity, physical examination, CT, and operative findings. RESULTS: Two thousand eight hundred and ninety-nine patients had CT scans, 156 (5.4%) of whom had isolated FF. The therapeutic operative group included 13 patients; 9 had immediate operation and 4 failed nonoperative management. The nonoperative/nontherapeutic operation group consisted of 142 patients with successful nonoperative management and 1 patient with a nontherapeutic operation. Abdominal tenderness was documented in 69% of the therapeutic operative group and 23% of the nonoperative/nontherapeutic group (odds ratio = 7.5; p < 0.001). The presence of a moderate to large amount of FF was increased in the therapeutic operative group (85% vs 8%; odds ratio = 66; p < 0.001). CONCLUSIONS: Isolated FF was noted in 5.4% of stable blunt trauma patients. Blunt trauma patients with moderate to large amounts of FF without solid organ injury on CT and abdominal tenderness should undergo immediate operative exploration. Patients with neither of these findings can be safely observed. PMID- 25127511 TI - Long-term health-related quality of life after iatrogenic bile duct injury repair. AB - BACKGROUND: Data on the effect of bile duct injuries (BDI) on health-related quality of life (HRQOL) are not well defined. We sought to assess long-term HRQOL after BDI repair in a large cohort of patients spanning a 23-year period. STUDY DESIGN: We identified and mailed HRQOL questionnaires to all patients treated for major BDI after laparoscopic cholecystectomy between January 1, 1990 and December 31, 2012 at Johns Hopkins Hospital. RESULTS: We identified 167 patients alive at the time of the study who met the inclusion criteria. Median age at BDI was 42 years (interquartile range 31 to 54 years); the majority of patients were female (n = 131 [78.4%]) and of white race (n = 137 [83.0%]). Most patients had Bismuth level 2 (n = 56 [33.7%]) or Bismuth level 3 (n = 40 [24.1%]) BDI. Surgical repair most commonly involved a Roux-en-Y hepaticojejunostomy (n = 142 [86.1%]). Sixty two patients (37.1%) responded to the HRQOL questionnaire. Median follow-up was 169 months (interquartile range 125 to 222 months). At the time of BDI, mental health was most affected, with patients commonly reporting a depressed mood (49.2%) or low energy level (40.0%). These symptoms improved significantly after definitive repair (both p < 0.05). Limitations in physical activity and general health remained unchanged before and after surgical repair (both p > 0.05). CONCLUSIONS: Mental health concerns were more commonplace vs physical or general health issues among patients with BDI followed long term. Optimal multidisciplinary management of BDI can help restore HRQOL to preinjury levels. PMID- 25127514 TI - The effects of a modified spinal mobilisation with leg movement (SMWLM) technique on sympathetic outflow to the lower limbs. AB - Physiotherapy management of lumbar disorders, based on Mulligan's mobilization techniques, is a treatment of choice by many physiotherapists, however, there is only limited evidence of any neurophysiological effects and much of this has focused on the cervical spine and upper limbs. This study aims to extend the knowledge base underpinning the use of a modified Mulligan's spinal mobilisation with leg movement technique (SMWLM) by exploring its effects on the peripheral sympathetic nervous system (SNS) of the lower limbs. Using a single blind, placebo controlled, independent groups study design, 45 normal naive healthy males were randomly assigned to one of three experimental groups (control, placebo or treatment; SMWLM). SNS activity was determined by recording skin conductance (SC) obtained from lower limb electrodes connected to a BioPac unit. Validation of the placebo technique was performed by post- intervention questionnaire. Results indicated that there was a significant change in SC from baseline levels (30%) that was specific to the side treated for the treatment group during the intervention period (compared to placebo and control conditions). This study provides preliminary evidence that a modified SMWLM technique results in side-specific peripheral SNS changes in the lower limbs. PMID- 25127512 TI - The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5 RNA interaction and filament assembly. AB - Cytoplasmic pattern recognition receptors detect non-self RNAs during virus infections and initiate antiviral signaling. One receptor, MDA5, possesses essential signaling domains, but weak RNA binding. A second receptor, LGP2, rapidly detects diverse dsRNA species, but lacks signaling domains. Accumulating evidence suggests LGP2 and MDA5 work together to detect viral RNA and generate a complete antiviral response, but the basis for their cooperation has been elusive. Experiments presented here address this gap in antiviral signaling, revealing that LGP2 assists MDA5-RNA interactions leading to enhanced MDA5 mediated antiviral signaling. LGP2 increases the initial rate of MDA5-RNA interaction and regulates MDA5 filament assembly, resulting in the formation of more numerous, shorter MDA5 filaments that are shown to generate equivalent or greater signaling activity in vivo than the longer filaments containing only MDA5. These findings provide a mechanism for LGP2 coactivation of MDA5 and a biological context for MDA5-RNA filaments in antiviral responses. PMID- 25127513 TI - Lysine acetylation controls local protein conformation by influencing proline isomerization. AB - Gene transcription responds to stress and metabolic signals to optimize growth and survival. Histone H3 (H3) lysine 4 trimethylation (K4me3) facilitates state changes, but how levels are coordinated with the environment is unclear. Here, we show that isomerization of H3 at the alanine 15-proline 16 (A15-P16) peptide bond is influenced by lysine 14 (K14) and controls gene-specific K4me3 by balancing the actions of Jhd2, the K4me3 demethylase, and Spp1, a subunit of the Set1 K4 methyltransferase complex. Acetylation at K14 favors the A15-P16trans conformation and reduces K4me3. Environmental stress-induced genes are most sensitive to the changes at K14 influencing H3 tail conformation and K4me3. By contrast, ribosomal protein genes maintain K4me3, required for their repression during stress, independently of Spp1, K14, and P16. Thus, the plasticity in control of K4me3, via signaling to K14 and isomerization at P16, informs distinct gene regulatory mechanisms and processes involving K4me3. PMID- 25127515 TI - [11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter. AB - INTRODUCTION: Positron emission tomography (PET) imaging of the norepinephrine transporter (NET) is still hindered by the availability of useful PET imaging probes. The present study describes the radiosynthesis and pre-clinical evaluation of a new compound, exo-3-(6-methoxypyridin-2-yloxy)-8-H-8 azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [(11)C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [(11)C]methanolate in a Boc protected precursor. The isolated [(11)C]NS8880 was evaluated pre-clinically both in a pig model (PET scanning) and in a rat model (MUPET scanning) and compared to (S,S)-[(11)C]-O-methylreboxetine ([(11)C]MeNER). RESULTS: The radiolabeling technique yielded [(11)C]NS8880 in low (<10%) but still useful yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [(11)C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [(11)C]NS8880. CONCLUSION: Based on the pre-clinical results obtained so far [(11)C]NS8880 displays promising properties for PET imaging of NET. PMID- 25127516 TI - Theory of dynamical electron channeling contrast images of near-surface crystal defects. AB - This paper describes the dynamical simulation of electron channeling contrast images (ECCIs) of dislocations. The approach utilizes both the Bloch wave formalism and the scattering matrix formalism to generate electron channeling patterns (ECPs). The latter formalism is then adapted to include the effect of lattice defects on the back-scattered electron yield, resulting in a computational algorithm for the simulation of ECCIs. Dislocations of known line direction and Burgers vector are imaged experimentally by ECCI and match well with simulated ECCIs for various channeling conditions. Experiment/simulation comparisons for ECPs and ECCIs are demonstrated for metals (Al), semiconductors (Si), and ceramics (SrTiO3). PMID- 25127517 TI - Effect of surface stress on microcantilever resonance frequency during water adsorption: influence of microcantilever dimensions. AB - This paper reports the effect of dimensions of microcantilever (MC) on its resonance frequency and bending upon adsorption of water molecules. Study is conducted on three MCs having the dimensions of 450 * 40 * 2.5 MUm(3) (MC1), 225 * 30 * 3 MUm(3) (MC2) and 125 * 35 * 4.5 MUm(3) (MC3). The measured resonant frequency showed the expected negative shift in MC1, initially positive followed by a negative shift in MC2 and only positive shift in MC3 during adsorption. This behavior is attributed to changes in the stiffness of the MC associated with the surface stress. The surface stress generated on the MC has been derived from its bending measurements upon water adsorption. The change in the stiffness of MC evaluated from an independent estimate of expected frequency shift showed that the relative stiffness change of MC increases linearly with the surface stress scaled with cube of width to height ratio of MCs, confirming the dimensional dependence of adsorption induced stiffness change. PMID- 25127518 TI - Validation and application of an UPLC-MS/MS method for the quantification of synthetic cannabinoids in urine samples and analysis of seized materials from the Portuguese market. AB - An UPLC-MS/MS method using ESI+ionization and MRM was developed and fully validated according to international guidelines for the qualitative and quantitative analysis of nine synthetic cannabinoids and/or their metabolites in urine samples (1mL). Prior to extraction the samples were subjected to an enzymatic hydrolysis using beta-glucuronidase followed by a SPE procedure using Oasis((r)) HLB 3cc (60mg) columns. The chromatographic separation was performed with an Acquity UPLC((r)) HSS T3 (50mm*2.1mm i.d., 1.8MUm) reversed-phase column using a gradient with methanol-ammonium formate 2mM (0.1% formic acid) and with a run time of 9.5min. The method was validated in terms of selectivity, capacity of identification, limits of detection (0.01-0.5ng/mL) and quantification (0.05 0.5ng/mL), recovery (58-105%), carryover, matrix effect, linearity (0.05 50ng/mL), intra-assay precision, inter-assay accuracy and precision (CV<20%). The method was applied to 80 authentic samples, five of them (6.2%) were confirmed or suspected to be positive for the metabolites JWH-018 N-hydroxypentyl and JWH-018 N-pentanoic acid of JWH-018 and for the metabolite JWH-122 N-(5-hydroxypentyl) of JWH-122, and three of them in association with THC and/or THCCOOH (substances included in the method, together with the 11-OH-THC). Additionally, 17 spice products were analyzed, for which were confirmed the presence of the following substances: AM-2201, JWH-018, JWH-022 JWH-073, JWH-122, JWH-203, JWH-210, JWH 250, HU-210 and RCS-4, according to the comparison with authentic reference material and published data. The analytical method developed allowed the analysis of synthetic cannabinoids and the notification of the first cases in Portugal. PMID- 25127519 TI - Accident rates amongst regular bicycle riders in Tasmania, Australia. AB - PURPOSE: To characterise the demographics, cycling habits and accident rates of adult cyclists in Tasmania. METHODS: Volunteers >=18 years of age who had cycled at least once/week over the previous month provided information on demographics; cycling experience; bicycles owned; hours/km/trips cycled per week; cycling purpose; protective equipment used; and major (required third-party medical treatment or resulted >=1 day off work) or minor (interfered with individuals' regular daily activities and/or caused financial costs) accidents while cycling. RESULTS: Over 8-months, 136 cyclists (70.6% male) completed the telephone survey. Mean (standard deviation) age was 45.4 (12.1) years with 17.1 (11.4) years of cycling experience. In the week prior to interview, cyclists averaged 6.6 trips/week (totalling 105.7km or 5.0h). The most common reason for cycling was commuting/transport (34% of trips), followed by training/health/fitness (28%). The incidence of major and minor cycling accidents was 1.6 (95% CI 1.1-2.0) and 3.7 (2.3-5.0) per 100,000km, respectively. Male sex was associated with a significantly lower minor accident risk (incidence rate ratio=0.34, p=0.01). Mountain biking was associated with a significantly higher risk of minor accident compared with road or racing, touring, and city or commuting biking (p<0.05). CONCLUSIONS: Physical activity of regular cyclists' exceeds the level recommended for maintenance of health and wellbeing; cyclists also contributed substantially to the local economy. Accident rates are higher in this sample than previously reported in Tasmania and internationally. Mountain biking was associated with higher risks of both major and minor accidents compared to road/racing bike riding. PMID- 25127520 TI - Is air quality index associated with cardiometabolic risk factors in adolescents? The CASPIAN-III Study. AB - OBJECTIVE: This study aims to evaluate the association of air quality index (AQI) with cardiometabolic risk factors in a nationally representative sample of healthy adolescents. METHODS: This nationwide survey was conducted among a stratified multi-stage probability sample of students, aged 10-18 years, from 27 provinces of Iran. Those students with history of any acute or chronic diseases, any medication use, as well as active or passive smoking were not included to the current study. Dietary and physical activity habits were documented by valid questionnaires. Physical examination and blood sampling were conducted under standard protocols. AQI data were obtained from air pollution monitoring sites from the entire country by considering air pollutants concentration, which includes all provincial counties containing different clusters. RESULTS: The study participants consisted of 1413 students (48.8% boys) with a mean (SD) age of 14.81+/-2.48 years. The mean AQI level was 285.37+/-30.11 at national levels. After adjustment for confounding factors including age, sex, and anthropometric measures, as well as for dietary and physical activity habits, multiple linear regressions based on correlation of coefficients of the AQI with cardiometabolic risk factors showed significant positive correlations of AQI with systolic blood pressure, fasting blood glucose, total cholesterol, LDL-cholesterol, and triglycerides, as well as significant negative correlations with HDL-cholesterol. After adjustment for abovementioned confounding factors, binary logistic regressions analyses showed that AQI increased the risk of abnormal levels of some risk factors as elevated levels of systolic blood pressure, total cholesterol, and triglycerides. CONCLUSION: The associations of low air quality with some cardiometabolic factors in the current survey, although not strong, might be considered as an evidence of the adverse cardiometabolic consequences of exposure to air pollutants in the pediatric age group, and predisposing them to earlier development of non-communicable diseases. PMID- 25127521 TI - Determinants of bisphenol A and phthalate metabolites in urine of Flemish adolescents. AB - As part of the second Flemish Environment and Health Study (FLEHS II), bisphenol A (BPA) and different phthalate metabolites were analyzed, for the first time, in the urine of 210 adolescents in Flanders, Belgium. All chemicals had a detection frequency above 90%. For all compounds, except the sum of DEHP, highest levels were detected during spring. Average values for the Flemish adolescents were in an agreement with concentrations found in different international studies, all confirming the ubiquity of BPA and phthalate exposure. There was a significant correlation between BPA and the different phthalate metabolites (r between 0.26 and 0.39; p<0.01). Shared sources of exposure to BPA and phthalates, such as food packaging, were suggested to be responsible for this positive correlation. Different determinants of exposure were evaluated in relation to the urinary concentrations of these chemicals. For BPA, a significant association was observed with household income class, smoking and exposure to environmental tobacco smoke. For phthalates, the following significant associations were observed: age (MBzP), educational level of the adolescent (MBzP), equivalent household income (MnBP), use of personal care products (MnBP and MBzP), wall paper in house (MnBP and MBzP) and use of local vegetables (MnBP and MBzP). PMID- 25127522 TI - A new and sensitive method for measuring in vivo and in vitro cytotoxicity in earthworm coelomocytes by flow cytometry. AB - This study describes a new and sensitive method for measuring the in vivo and in vitro cytotoxicity of 2 earthworm species, Eisenia andrei and Perionyx excavatus, exposed to copper. Specifically, we measured the number of coelomocyte cells that were affected by copper following in vivo and in vitro exposure by flow cytometry, after calcein acetoxymethyl ester (calcein-AM) staining. We found that the coelomocyte viability of both earthworm species was noticeably reduced in the in vivo cytotoxicity test at concentrations of 100mg/kg copper in dry soil. However, pathological symptoms, such as mucous secretion and bleeding, swelling, thinning, and fragmentation, and burrowing symptoms were not evident following exposure to copper levels of <400mg/kg dry soil. In conclusion, the present study demonstrates that calcein-AM is a more sensitive test of earthworm coelomocyte cytotoxicity compared to the traditional individual level toxicity test. Therefore, this test could be used to detect low levels of metal contamination in soils. PMID- 25127523 TI - Temperature-related mortality in 17 large Chinese cities: how heat and cold affect mortality in China. AB - Few multicity studies have been conducted to investigate the acute health effects of cold and hot temperatures in China. We aimed to examine the relationship between temperature and daily mortality in 17 large Chinese cities. We first calculated city-specific effect of temperature using time-series regression models combined with distributed lag nonlinear models; then we pooled the city specific estimates with the Bayesian hierarchical models. The cold effects lasted longer than the hot effects. For the cold effects, a 1 degrees C decrease from the 25th to 1st percentiles of temperature over lags 0-14 days was associated with increases of 1.69% [95% posterior intervals (PI): 1.01%, 2.36%], 2.49% (95% PI: 1.53%, 3.46%) and 1.60% (95% PI: 0.32%, 2.87%) in total, cardiovascular and respiratory mortality, respectively. For the hot effects, a 1 degrees C increase from the 75th to 99th percentiles of temperature was associated with corresponding increases of 2.83% (95% PI: 1.42%, 4.24%), 3.02% (95% PI: 1.33%, 4.71%) and 4.64% (95% PI: 1.96%, 7.31%). The latitudes, number of air conditioning per household and disposable income per capita were significant modifiers for cold effects; the proportion of the elderly was a significant modifier for hot effects. This largest epidemiological study of temperature to date in China suggested that both cold and hot temperatures were associated with increased mortality. Our findings may have important implications for the public health policies in China. PMID- 25127524 TI - Temporal trends of radio-frequency electromagnetic field (RF-EMF) exposure in everyday environments across European cities. AB - BACKGROUND: The rapid development and increased use of wireless telecommunication technologies led to a substantial change of radio-frequency electromagnetic field (RF-EMF) exposure in the general population but little is known about temporal trends of RF-EMF in our everyday environment. OBJECTIVES: The objective of our study is to evaluate temporal trends of RF-EMF exposure levels in different microenvironments of three European cities using a common measurement protocol. METHODS: We performed measurements in the cities of Basel (Switzerland), Ghent and Brussels (Belgium) during one year, between April 2011 and March 2012. RF-EMF exposure in 11 different frequency bands ranging from FM (Frequency Modulation, 88 MHz) to WLAN (Wireless Local Area Network, 2.5 GHz) was quantified with portable measurement devices (exposimeters) in various microenvironments: outdoor areas (residential areas, downtown and suburb), public transports (train, bus and tram or metro rides) and indoor places (airport, railway station and shopping centers). Measurements were collected every 4s during 10-50 min per environment and measurement day. Linear temporal trends were analyzed by mixed linear regression models. RESULTS: Highest total RF-EMF exposure levels occurred in public transports (all public transports combined) with arithmetic mean values of 0.84 V/m in Brussels, 0.72 V/m in Ghent, and 0.59 V/m in Basel. In all outdoor areas combined, mean exposure levels were 0.41 V/m in Brussels, 0.31 V/m in Ghent and 0.26 V/m in Basel. Within one year, total RF-EMF exposure levels in all outdoor areas in combination increased by 57.1% (p<0.001) in Basel by 20.1% in Ghent (p=0.053) and by 38.2% (p=0.012) in Brussels. Exposure increase was most consistently observed in outdoor areas due to emissions from mobile phone base stations. In public transports RF-EMF levels tended also to increase but mostly without statistical significance. DISCUSSION: An increase of RF-EMF exposure levels has been observed between April 2011 and March 2012 in various microenvironments of three European cities. Nevertheless, exposure levels were still far below regulatory limits of each country. A continuous monitoring is needed to identify high exposure areas and to anticipate critical development of RF-EMF exposure at public places. PMID- 25127525 TI - Nonylphenol in pregnant women and their matching fetuses: placental transfer and potential risks of infants. AB - As the predominant environmental biodegradation product of nonylphenol (NP) ethoxylates and with proven estrogenic effects, NP is formed during the alkylation process of phenols. The purposes of this study were (1) to examine maternal and prenatal exposure to NP in Taiwan, (2) to determine the level of placental protection against NP exposure as well as the level of NP in breast milk, and (3) to assess the potential risk for breastfed newborns exposed to NP through the milk. Thirty pairs of maternal and fetal blood samples, placenta, and breast milk during the 1st and the 3rd months of lactation were collected. External NP exposures of these specimens were then analyzed by using high performance liquid chromatography coupling with fluorescence detection. Next, the socio-demographics, lifestyle, delivery method, dietary and work history were collected using a questionnaire. In addition, the daily intake of NP from consuming breast milk in the 1st and 3rd months for newborns was studied through deterministic and probabilistic risk assessment methods. The geometric means and geometric standard deviation of NP levels in maternal blood, fetal cord blood, placenta, and breast milk in the 1st and 3rd months were 14.6 (1.7) ng/ml, 18.8 (1.8) ng/ml, 19.8 (1.9) ng/g, 23.5 (3.2) ng/ml, and 57.3 (1.4) ng/ml, respectively. The probabilistic percentiles (50th, 75th, and 95th) of daily intake NP in breast milk were 4.33, 7.79, and 18.39 MUg/kg-bw/day in the 1st month, respectively, and were 8.11, 10.78, 16.08 MUg/kg-bw/day in the 3rd month, respectively. The probabilistic distributions (5th, 25th, and 50th) of risk for infants aged 1 month old were 0.27, 0.64, and 1.15, respectively, and that for infants aged 3 month old were 0.31, 0.46, and 0.62, respectively. Through repeated exposure from the dietary intake of expectant mothers, fetuses could encounter a high NP exposure level due to transplacental absorption, partitioning between the maternal and fetal compartments. Daily NP intake via breast milk in three month-old babies exceeded the tolerable daily intake (TDI) of 5 ug/kg bw/day indicated a potential risk for Taiwan infants. PMID- 25127526 TI - A computed tomography evaluation of two hundred normal ankles, to ascertain what anatomical landmarks to use when compressing or placing an ankle syndesmosis screw. AB - Classical AO teaching recommends that a syndesmosis screw should be inserted at 25-30 degrees to the coronal plane of the ankle. Accurately judging the 25/30 degree angle can be difficult, resulting in poor operative reduction of syndesmosis injuries. The CT scans of 200 normal ankles were retrospectively examined. The centroid of the fibula and tibia in the axial plane 15mm proximal to the talar dome was calculated. A force vector between the centroid of the fibula and the tibia in the axial plane should not displace the fibula relative to the tibia when surfaces are parallel. Therefore, a line connecting the two centroids was postulated to be the ideal syndesmosis line. This line was shown to pass through the fibula within 2.5mm of the lateral cortical apex of the fibula and the anterior half of the medial malleolus in 100% of the ankles studied. The results support the concept that in the operatively reduced syndesmosis, the anterior half of the medial malleolus can be used as a reliable guide for aiming the syndesmosis drill hole, provided that the fibular entry point is at/or adjacent to the lateral fibular apex. The screw should also remain parallel to the tibial plafond in the coronal plane. PMID- 25127527 TI - Intracellular Haemophilus influenzae invades the brain: is zyxin a critical blood brain barrier component regulated by TNF-alpha? PMID- 25127528 TI - Polyphosphate-mediated modulation of Campylobacter jejuni biofilm growth and stability. AB - Biofilms increase C. jejuni's resilience to detergents, antibiotics, and environmental stressors. In these investigations, we studied the modulation of biofilm in response to phosphate related stressors. We found that the deletion of ppk1, phoX, and ppk2 (polyphosphate associated [poly P] genes) in C. jejuni modulated different stages of biofilm formation such as attached microcolonies, air-liquid biofilms, and biofilm shedding. Additionally, inorganic phosphate also modulated attached microcolonies, air-liquid biofilms, and biofilm shedding both independently of and additively in the poly P associated mutants. Furthermore, we observed that these different biofilm stages were affected by biofilm age: for example, the adherent microcolonies were maximum on day 2, while biofilm growth at the air-liquid interface and shedding was highest on day 3. Also, we observed altered calcofluor white reactive polysaccharides in poly P-associated mutants, as well as increased secretion of autoinducer-2 (AI-2) quorum sensing molecules in the ?ppk2 mutant. Further, the polysaccharide and flagellar biosynthesis genes, that are associated with biofilm formation, were altered in these poly P associated mutants. We conclude that the phosphate limiting condition modulates C. jejuni biofilm formation. PMID- 25127529 TI - Cardiorespiratory fitness and cardiovascular burden in chronic kidney disease. AB - OBJECTIVES: Reduced functional capacity is associated with poor prognosis. In patients with chronic kidney disease the factors that contribute to low cardiorespiratory fitness are unclear. The objective of this study was to evaluate the cardiorespiratory and cardiovascular response to exercise in chronic kidney disease patients, and secondly investigate the relationships between cardiorespiratory fitness and cardiovascular burden. DESIGN: Cross-sectional analysis. METHODS: Baseline demographic, anthropometric and biochemical data were examined in 136 patients with moderate chronic kidney disease (age 59.7+/-9.6yrs, eGFR 40+/-9ml/min/1.73m(2), 55% male, 39% with a history of cardiovascular disease, 38% diabetic and 17% current smokers). Cardiorespiratory fitness was measured as peak VO2, left ventricular morphology and function using echocardiography, central arterial stiffness by aortic pulse wave velocity and left ventricular afterload using augmentation index. Physical activity levels were assessed using the Active Australia questionnaire. RESULTS: Peak VO2 (22.9+/ 6.5ml/kg/min) and peak heart rate (148+/-22bpm) were 17% and 12% lower than the age-predicted values, respectively. The low fit group were significantly older, and were more likely to have type II diabetes, cardiovascular disease, a higher BMI and be less active than the high fit group (P<0.05). The independent predictors of peak VO2 were age, type II diabetes, hemoglobin level, physical activity, aortic pulse wave velocity, augmentation index, and global longitudinal strain. CONCLUSIONS: In patients with chronic kidney disease, the peak VO2 and heart rate response is markedly impaired. Reduced cardiorespiratory fitness is independently associated with increased aortic stiffness, increased left ventricle afterload, poor left ventricle function and higher burden of cardiovascular risk. PMID- 25127530 TI - Effects of femoral rotational taping on pain, lower extremity kinematics, and muscle activation in female patients with patellofemoral pain. AB - OBJECTIVES: To explore the hip and knee joint kinematics as well as muscle activation between participants with patellofemoral pain syndrome (PFPS) and controls, and to investigate the immediate effect of proximal femoral rotational taping on pain, joint kinematics, and muscle activation during single-leg squat (SLS). DESIGN: Cross-sectional study. METHODS: Sixteen female participants with PFPS, and eight healthy female controls participated. Three-dimensional hip and patellar kinematics measured by electromagnetic tracking system, hip (gluteus maximus and gluteus medius) and thigh (rectus femoris) muscle activation measured by EMG, and subjective report of pain were recorded during SLS in three randomized conditions of no tape, sham taping, and femoral rotational taping with kinesiotape. RESULTS: Without taping, compared with controls, PFPS group had increased hip adduction angle (23.5+/-11.3 degrees vs. 15.8+/-7.3 degrees ) during SLS. Additionally, PFPS group exhibited lesser rectus femoris activity during the initial 0-15 degrees of SLS. Application of both femoral rotational and sham tapes reduced pain for PFPS group. Compared with no tape or sham tape, femoral rotational tape significantly shifted the patella into more posterior (1.59+/-0.83cm in no tape vs. 1.54+/-0.87cm in sham tape vs. 1.32+/-0.72cm in femoral rotational tape) and distal (-2.49+/-0.95cm vs. -2.64+/-0.80cm vs. 3.11+/-0.77cm) positions in the PFPS group. CONCLUSIONS: Femoral rotational taping could alter patellofemoral kinematics and decrease pain in treatment of young female participants with PFPS. PMID- 25127532 TI - Traumatic lens subluxation presenting as pseudomelanoma. AB - An 82-year-old white man was referred for a suspected inferior pigmented, choroidal melanoma in his left eye. The patient stated that his left eye had been hit by a tree branch approximately 40 years prior, and he had not been able to see with it since then. Dilated fundus examination revealed a 14 * 8 mm dark, dome-shaped choroidal mass located inferiorly. Transillumination of the eye revealed no defects. Ultrasonography revealed a hollow lesion, consistent with a senile, dark dislocated cataract. PMID- 25127534 TI - Immigrant and refugee health: foreward. PMID- 25127531 TI - Aberrant hetero-disulfide bond formation by the hypertriglyceridemia-associated p.Gly185Cys APOA5 variant (rs2075291). AB - OBJECTIVE: Apolipoprotein A-V (apoA-V) is a low-abundance plasma protein that modulates triacylglycerol homeostasis. Gene transfer studies were undertaken in apoa5 (-/-) mice to define the mechanism underlying the correlation between the single-nucleotide polymorphism c.553G>T in APOA5 and hypertriglyceridemia. APPROACH AND RESULTS: Adeno-associated virus (AAV) 2/8-mediated gene transfer of wild-type apoA-V induced a dramatic lowering of plasma triacylglycerol in apoa5 ( /-) mice, whereas AAV2/8-Gly162Cys apoA-V (corresponding to the c.553G>T single nucleotide polymorphism: rs2075291; p.Gly185Cys when numbering includes signal sequence) had a modest effect. Characterization studies revealed that plasma levels of wild-type and G162C apoA-V in transduced mice were similar and within the physiological range. Fractionation of plasma from mice transduced with AAV2/8 G162C apoA-V indicated that, unlike wild-type apoA-V, >50% of G162C apoA-V was recovered in the lipoprotein-free fraction. Nonreducing SDS-PAGE immunoblot analysis provided evidence that G162C apoA-V present in the lipoprotein-free fraction, but not that portion associated with lipoproteins, displayed altered electrophoretic mobility consistent with disulfide-linked heterodimer formation. Immunoprecipitation followed by liquid chromatography/mass spectrometry of human plasma from subjects homozygous for wild-type APOA5 and c.553G>T APOA5 revealed that G162C apoA-V forms adducts with extraneous plasma proteins including fibronectin, kininogen-1, and others. CONCLUSIONS: Substitution of Cys for Gly at position 162 of mature apoA-V introduces a free cysteine that forms disulfide bonds with plasma proteins such that its lipoprotein-binding and triacylglycerol modulation functions are compromised. PMID- 25127533 TI - Severe bilateral ischemic retinal vasculitis following cataract surgery. AB - This report describes two cases of severe, bilateral ischemic retinal vasculitis following cataract surgeries at different surgical centers. In both cases, the patient underwent bilateral cataract surgeries, performed 1 week apart for each eye. In the perioperative period following the second of the two surgeries, both patients developed severe, bilateral intraocular inflammation and profound vision loss. The underlying cause of this adverse response remains unknown. The authors suggest that the severe inflammatory reaction could be related to an intraoperative intracameral vancomycin injection. PMID- 25127536 TI - Immigrant and refugee health: mental health conditions. AB - Immigrants leave their homes for unfamiliar destinations in search of better lives for themselves and their families. Many immigrants experience profound loss and emotional distress as they adjust to life in different societies. Despite these challenges, the prevalence of mental health conditions among immigrants is low, whereas children of immigrants have rates equal to those of native populations. The prevalence of mental health conditions is high among refugees, who comprise a specific subgroup of immigrants who have been displaced forcibly and often have experienced severe trauma. Cultural factors, such as stigma and somatization of emotional symptoms, make it less likely that immigrants and refugees from certain groups will ever present to mental health subspecialists. Strong therapeutic relationships, cultural sensitivity, involvement of family members, judicious use of medications, and knowledge of available community resources are important tools that can aid clinicians who treat immigrants and refugees with mental health conditions. PMID- 25127535 TI - Immigrant and refugee health: medical evaluation. AB - Overseas medical screening by panel physicians for conditions that might jeopardize US public health is required for admission to the United States by immigrant visa or refugee status. According to protocols established by the Centers for Disease Control and Prevention, conditions such as active tuberculosis and substance dependence, when detected, prohibit entry to the United States, whereas close medical follow-up after arrival is required for individuals with other conditions. Refugees and asylees should undergo further medical assessment by a US civil surgeon as soon as possible after arrival. Applicants for legal permanent residence in the United States, whether by immigrant visa or adjustment of status, must receive vaccinations comparable to those recommended for citizens. When immigrants and refugees present to a primary care physician, the vaccination process may not be complete, and documentation of the extent to which it is complete might be lacking. Immigrants and refugees may have a variety of unrecognized or untreated musculoskeletal conditions, mental health conditions, infectious diseases, and chronic conditions. PMID- 25127537 TI - Immigrant and refugee health: common infectious diseases. AB - Immigrants and refugees are at risk of infectious diseases (IDs) that are rare in the United States. Screening and treatment before entry into the United States are required for some of these diseases, whereas quarantine is mandated for others. The Centers for Disease Control and Prevention has published specific recommendations for the evaluation and treatment of immigrants and refugees before and after they arrive in the United States. In addition, immigrants and refugees who return to their home countries are at greater risk of IDs than other travelers. Health care professionals are required to report certain IDs to state or local health departments. PMID- 25127538 TI - Immigrant and refugee health: cross-cultural communication. AB - Physicians in the United States increasingly care for culturally, linguistically, and educationally diverse immigrants with limited English proficiency. Language barriers contribute significantly to the health disparities experienced by patients with limited English proficiency. Qualified professional interpreters should be used instead of ad hoc interpreters, such as a patient's friend or family member, an untrained bilingual staff member, or a bilingual stranger. Children should not be used as interpreters. Physicians and other health care professionals must be fluent to communicate with patients in another language. Use of electronic translation systems should be avoided. Cultural competence refers to the attitudes, knowledge, and skills needed to work well in cross cultural situations and effectively provide care to diverse populations. Stereotypes are perpetuated when members of a group are assumed to share cultural values, beliefs, or attitudes. Attempting to memorize a list of what to do and what to avoid when working with any particular group is ineffective. Every patient's culture is multidimensional and dynamic and is not defined by race or language group. PMID- 25127539 TI - How do patients with severe mental diagnosis cope in everyday life - a qualitative study comparing patients' experiences of self-referral inpatient treatment with treatment as usual? AB - BACKGROUND: Several hospitals in Norway provide short self-referral inpatient treatment to patients with severe mental diagnosis. No studies have compared the experiences of patients who have had the opportunity to self-refer to inpatient treatment with patients who have received treatment as usual. This qualitative study was nested within a randomised controlled trial investigating the effect of self-referral to inpatient treatment. The aim was to explore how patients with severe mental diagnosis coped four months after signing a contract for self referral, as compared to patients receiving treatment as usual. METHODS: Data was collected using qualitative individual interviews with patients with severe mental diagnosis, conducted four months after being randomised either to a contract for self-referral (intervention group) or to treatment as usual (control group). RESULTS: Twenty-five patients participated in interviews - 11 from the intervention group and 14 from the control group. Results four months after randomisation showed that patients with a contract for self-referral appeared to have more confidence in strategies to cope with mental illness and to apply more active cognitive strategies. Patients with a contract also expressed less resignation, hopelessness and powerlessness than patients without a contract. In addition, patients with a contract seemed to be closer to the ideal of living a "normal" life and being a "normal" person. CONCLUSION: The results indicate that the patients who had a contract for self-referral had come further in the recovery process and should possibly be better off during treatment. PMID- 25127541 TI - Dominant side in single-leg stance stability during floor oscillations at various frequencies. AB - BACKGROUND: We investigated lateral dominance in the postural stability of single leg stance with anteroposterior floor oscillations at various frequencies. METHODS: Thirty adults maintained a single-leg stance on a force platform for 20 seconds per trial. Trials were performed with no oscillation (static condition) and with anteroposterior floor oscillations (2.5-cm amplitude) at six frequencies: 0.25, 0.5, 0.75, 1.0, 1.25 and 1.5 Hz (dynamic condition). A set of three trials was performed on each leg in each oscillation frequency in random order. The mean speed of the center of pressure in the anteroposterior direction (CoPap) was calculated as an index of postural stability, and frequency analysis of CoPap sway was performed. Footedness for carrying out mobilizing activities was assessed with a questionnaire. RESULTS: CoPap speed exponentially increased as oscillation frequency increased in both legs. The frequency analysis of CoPap showed a peak <0.3 Hz at no oscillation. The frequency components at 0.25-Hz oscillation included common components with no oscillation and those at 1.5-Hz oscillation showed the maximum amplitude among all conditions. Postural stability showed no significant difference between left- and right-leg stance at no oscillation and oscillations <=1.25 Hz, but at 1.5-Hz oscillation was significantly higher in the right-leg stance than in the left-leg stance. For the lateral dominance of postural stability at individual levels, the lateral difference in postural stability at no oscillation was positively correlated with that at 0.25-Hz oscillation (r = 0.51) and negatively correlated with that at 1.5 Hz oscillation (r = -0.53). For 70% of subjects, the dominant side of postural stability was different at no oscillation and 1.5-Hz oscillation. In the subjects with left- or right-side dominance at no oscillation, 94% or 38% changed their dominant side at 1.5-Hz oscillation, with a significant difference between these percentages. In the 1.5-Hz oscillation, 73% of subjects had concordance between the dominant side of postural stability and that of mobilizing footedness. CONCLUSION: In static conditions, there was no lateral dominance of stability during single-leg stance. At 1.5-Hz oscillation, the highest frequency, right side dominance of postural stability was recognized. Functional role in supporting leg may be divided between left and right legs according to the change of balance condition from static to dynamic. PMID- 25127543 TI - The laboratory diagnosis of mucopolysaccharidosis III (Sanfilippo syndrome): A changing landscape. AB - Mucopolysaccharidosis type III (MPS III) is characterized by progressive neurological deterioration, behavioral abnormalities, a relatively mild somatic phenotype, and early mortality. Because of the paucity of somatic manifestations and the rarity of the disease, early diagnosis is often difficult. Therapy targeting the underlying disease pathophysiology may offer the greatest clinical benefit when started prior to the onset of significant neurologic sequelae. Here we review current practices in the laboratory diagnosis of MPS III in order to facilitate earlier patient identification and diagnosis. When clinical suspicion of MPS III arises, the first step is to order a quantitative assay that screens urine for the presence of glycosaminoglycan biomarkers using a spectrophotometric compound (e.g., dimethylmethylene blue). We recommend testing all patients with developmental delay and/or behavioral abnormalities as part of the diagnostic work-up because quantitative urine screening is inexpensive and non-invasive. Semi-quantitative urine screening assays using cationic dyes on filter paper (e.g., spot tests) have relatively high rates of false-positives and false negatives and are obsolete. Of note, a negative urinary glycosaminoglycan assay does not necessarily rule out MPS because, in some patients, an overlap in excretion levels with healthy controls may occur. All urine samples that test positive for glycosaminoglycans with a quantitative assay should be confirmed by electrophoresis, thin layer chromatography, or tandem mass spectrometry, which further improves the sensitivity and specificity. The gold standard for diagnosis remains the enzyme activity assay in cultured skin fibroblasts, leukocytes, plasma, or serum, which can be used as a first-line diagnostic test in some regions. Molecular genetic analysis should be offered to all families of patients to allow genetic counseling for informed family planning. For a small number of variants, genotype-phenotype correlations are available and can offer prognostic value. Prenatal testing via enzyme activity assay in chorionic villi or amniotic fluid cells is available at a limited number of centers worldwide, but whenever possible, a molecular genetic analysis is preferred for prenatal diagnosis. To conclude, we discuss the development of newborn screening assays in dried blood spots and high-throughput methods for sequencing the protein-coding regions of the genome (whole exome sequencing) and their relevance to future changes in the MPS III diagnostic landscape. PMID- 25127540 TI - Lung transplantation in idiopathic pulmonary fibrosis: a systematic review of the literature. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a distinct form of interstitial pneumonia with unknown origin and poor prognosis. Current pharmacologic treatments are limited and lung transplantation is a viable option for appropriate patients. The aim of this review was to summarize lung transplantation survival in IPF patients overall, between single (SLT) vs. bilateral lung transplantation (BLT), pre- and post Lung Allocation Score (LAS), and summarize wait-list survival. METHODS: A systematic review of English language studies published in Medline or Embase between 1990 and 2013 was performed. Eligible studies were those of observational design reporting survival post-lung transplantation or while on the wait list among IPF patients. RESULTS: Median survival post-transplantation among IPF patients is estimated at 4.5 years. From ISHLT and OPTN data, one year survival ranged from 75% - 81%; 3-year: 59% - 64%; and 5-year: 47% - 53%. Post-transplant survival is lower for IPF vs. other underlying pre-transplant diagnoses. The proportion of IPF patients receiving BLT has steadily increased over the last decade and a half. Unadjusted analyses suggest improved long-term survival for BLT vs. SLT; after adjustment for patient characteristics, the differences tend to disappear. IPF patients account for the largest proportion of patients on the wait list and while wait list time has decreased, the number of transplants for IPF patients has increased over time. OPTN data show that wait list mortality is higher for IPF patients vs. other diagnoses. The proportion of IPF patients who died while awaiting transplantation ranged from 14% to 67%. While later transplant year was associated with increased survival, no significant differences were noted pre vs. post LAS implementation; however a high LAS vs low LAS was associated with decreased one-year survival. CONCLUSIONS: IPF accounts for the largest proportion of patients awaiting lung transplants, and IPF is associated with higher wait list and post-transplant mortality vs. other diagnoses. Improved BLT vs. SLT survival may be the result of selection bias. Survival pre- vs. post LAS appears to be similar except for IPF patients with high LAS, who have lower survival compared to pre-LAS. Data on post-transplant morbidity outcomes are sparse. PMID- 25127544 TI - The need for a research and development strategy. PMID- 25127542 TI - Long term effects of enzyme replacement therapy in an Italian cohort of type 3 Gaucher patients. AB - BACKGROUND: The chronic neuropathic form of Gaucher disease (GD3) is characterised by hepatosplenomegaly, anaemia, thrombocytopenia, bone alterations and central neurological involvement. Enzyme replacement therapy (ERT) has been demonstrated to be effective in non neuropathic Gaucher disease, but long term results in patients with GD3 are still limited and contrasting. A possible role of genotype in determining the response to ERT has been hypothesised. PATIENTS AND METHODS: All patients affected by GD3, treated with ERT, and followed-up in 4 different Italian centres (Udine, Catanzaro, Sassari and Florence) were included. Data on clinical conditions, laboratory values, neurological and neuropsychological examinations, radiological and electrophysiological features were collected retrospectively from clinical records. RESULTS: Ten patients (6 females, 4 males) with four different genotypes (L444P/L444P, L444P/F231I, P159T/unknown, C.115+1G>A/N188S) were identified. They received ERT infusions from 3 to 21years. Haematological parameters and organomegaly improved/normalised in all patients. Three patients showed severe progressive skeletal deformities. 6/10 patients were neurologically asymptomatic when they started ERT for systemic symptoms. During the follow-up, 2/6 developed an important central nervous system disease; 2/6 developed mild central symptoms; and 2/6 did not show any neurological symptom after 5, and 20years of treatment respectively, despite the presence of epileptiform abnormalities at the electroencephalogram. Overall, neurological involvement worsened over time in 6/10 patients, 3 of whom developed progressive myoclonic encephalopathy and died. CONCLUSIONS: ERT improved the systemic manifestations in patients with GD3, but was not able to counteract the progression of neurological symptoms in the long term. PMID- 25127545 TI - Simplified follow-up after medical abortion using a low-sensitivity urinary pregnancy test and a pictorial instruction sheet in Rajasthan, India--study protocol and intervention adaptation of a randomised control trial. AB - BACKGROUND: The World Health Organisation suggests that simplification of the medical abortion regime will contribute to an increased acceptability of medical abortion, among women as well as providers. It is expected that a home-based follow-up after a medical abortion will increase the willingness to opt for medical abortion as well as decrease the workload and service costs in the clinic. METHODS/DESIGN: This study protocol describes a study that is a randomised, controlled, non-superiority trial. Women screened to participate in the study are those with unwanted pregnancies and gestational ages equal to or less than nine weeks. The randomisation list will be generated using a computerized random number generator and opaque sealed envelopes with group allocation will be prepared. Randomization of the study participants will occur after the first clinical encounter with the doctor. Eligible women randomised to the home-based assessment group will use a low-sensitivity pregnancy test and a pictorial instruction sheet at home, while the women in the clinic follow-up group will return to the clinic for routine follow-up carried out by a doctor. The primary objective of the study this study protocol describes is to evaluate the efficacy of home-based assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet 10-14 days after an early medical abortion. Providers or research assistants will not be blinded during outcome assessment. To ensure feasibility of the self-assessment intervention an adaption phase took place at the selected study sites before study initiation. This resulted in an optimized, tailor-made intervention and in the development of the pictorial instruction sheet with a guide on how to use the low-sensitivity pregnancy test and the danger signs after a medical abortion. DISCUSSION: In this paper, we will describe the study protocol for a randomised control trial investigating the efficacy of simplified follow-up in terms of home-based assessment, 10-14 days after a medical abortion. Moreover, a description of the adaptation phase is included for a better understanding of the implementation of the intervention in a setting where literacy is low and the road-connections are poor. TRIAL REGISTRATION: Clinicaltrials.gov NCT01827995. Registered 04 May 2013. PMID- 25127546 TI - mRNA-based vaccines synergize with radiation therapy to eradicate established tumors. AB - BACKGROUND: The eradication of large, established tumors by active immunotherapy is a major challenge because of the numerous cancer evasion mechanisms that exist. This study aimed to establish a novel combination therapy consisting of messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate the effective treatment of established tumors with aggressive growth kinetics. METHODS: The combination of a tumor-specific mRNA-based vaccination with radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by the combination therapy was evaluated via gene expression arrays as well as flow cytometry analyses of tumor infiltrating cells. RESULTS: In both tumor models we demonstrated that a combination of mRNA-based immunotherapy with radiation results in a strong synergistic anti-tumor effect. This was manifested as either complete tumor eradication or delay in tumor growth. Gene expression analysis of mouse tumors revealed a variety of substantial changes at the tumor site following radiation. Genes associated with antigen presentation, infiltration of immune cells, adhesion, and activation of the innate immune system were upregulated. A combination of radiation and immunotherapy induced significant downregulation of tumor associated factors and upregulation of tumor suppressors. Moreover, combination therapy significantly increased CD4+, CD8+ and NKT cell infiltration of mouse tumors. CONCLUSION: Our data provide a scientific rationale for combining immunotherapy with radiation and provide a basis for the development of more potent anti-cancer therapies. PMID- 25127547 TI - Circulation of four Anaplasma phagocytophilum ecotypes in Europe. AB - BACKGROUND: Anaplasma phagocytophilum is the etiological agent of granulocytic anaplasmosis in humans and animals. Wild animals and ticks play key roles in the enzootic cycles of the pathogen. Potential ecotypes of A. phagocytophilum have been characterized genetically, but their host range, zoonotic potential and transmission dynamics has only incompletely been resolved. METHODS: The presence of A. phagocytophilum DNA was determined in more than 6000 ixodid ticks collected from the vegetation and wildlife, in 289 tissue samples from wild and domestic animals, and 69 keds collected from deer, originating from various geographic locations in The Netherlands and Belgium. From the qPCR-positive lysates, a fragment of the groEL-gene was amplified and sequenced. Additional groEL sequences from ticks and animals from Europe were obtained from GenBank, and sequences from human cases were obtained through literature searches. Statistical analyses were performed to identify A. phagocytophilum ecotypes, to assess their host range and their zoonotic potential. The population dynamics of A. phagocytophilum ecotypes was investigated using population genetic analyses. RESULTS: DNA of A. phagocytophilum was present in all stages of questing and feeding Ixodes ricinus, feeding I. hexagonus, I. frontalis, I. trianguliceps, and deer keds, but was absent in questing I. arboricola and Dermacentor reticulatus. DNA of A. phagocytophilum was present in feeding ticks and tissues from many vertebrates, including roe deer, mouflon, red foxes, wild boar, sheep and hedgehogs but was rarely found in rodents and birds and was absent in badgers and lizards. Four geographically dispersed A. phagocytophilum ecotypes were identified, that had significantly different host ranges. All sequences from human cases belonged to only one of these ecotypes. Based on population genetic parameters, the potentially zoonotic ecotype showed significant expansion. CONCLUSION: Four ecotypes of A. phagocytophilum with differential enzootic cycles were identified. So far, all human cases clustered in only one of these ecotypes. The zoonotic ecotype has the broadest range of wildlife hosts. The expansion of the zoonotic A. phagocytophilum ecotype indicates a recent increase of the acarological risk of exposure of humans and animals. PMID- 25127550 TI - Association among duration of mechanical ventilation, cuff material of endotracheal tube, and postoperative nosocomial pneumonia in cardiac surgical patients: a prospective study. AB - OBJECTIVES: Postoperative pulmonary complications are a burden for high-risk surgical patients with a risk of aspiration of subglottic secretions along the polyvinyl chloride cuff. The introduction of a polyurethane cuff diminishes secretion leakage with a decreased rate of pneumonia. The aim of the current analysis was to determine the time at which a polyurethane cuffed endotracheal tube might be advantageous to prevent aspiration in a setting of high-risk surgical patients. METHODS: The present investigation is based on published data obtained in postoperative cardiac surgical patients undergoing operation from 2006 to 2007. Cuff pressure was kept between 20 and 26 cmH2O intraoperatively and in the intensive care unit. The current post hoc analysis determines (1) the discriminatory cutoff value of intubation duration for predicting postoperative pneumonia and (2) the potential factors associated with prolonged intubation. RESULTS: Forty-three patients (32%) were diagnosed with early postoperative pneumonia. Receiver operating characteristics analysis revealed a cutoff value of 16.6 hours for the duration of mechanical ventilation to discriminate patients with postoperative pneumonia. A stepwise binary logistic regression analysis revealed that a polyvinyl chloride cuff was associated with a 10-fold increased risk for prolonged intubation. CONCLUSIONS: The current analyses provide evidence that among cardiac surgical patients, mechanical ventilation more than 16.6 hours is associated with an increased likelihood of postoperative pneumonia. PMID- 25127548 TI - Primary transcriptome map of the hyperthermophilic archaeon Thermococcus kodakarensis. AB - BACKGROUND: Prokaryotes have relatively small genomes, densely-packed with protein-encoding sequences. RNA sequencing has, however, revealed surprisingly complex transcriptomes and here we report the transcripts present in the model hyperthermophilic Archaeon, Thermococcus kodakarensis, under different physiological conditions. RESULTS: Sequencing cDNA libraries, generated from RNA isolated from cells under different growth and metabolic conditions has identified >2,700 sites of transcription initiation, established a genome-wide map of transcripts, and consensus sequences for transcription initiation and post transcription regulatory elements. The primary transcription start sites (TSS) upstream of 1,254 annotated genes, plus 644 primary TSS and their promoters within genes, are identified. Most mRNAs have a 5'-untranslated region (5'-UTR) 10 to 50 nt long (median = 16 nt), but ~20% have 5'-UTRs from 50 to 300 nt long and ~14% are leaderless. Approximately 50% of mRNAs contain a consensus ribosome binding sequence. The results identify TSS for 1,018 antisense transcripts, most with sequences complementary to either the 5'- or 3'-region of a sense mRNA, and confirm the presence of transcripts from all three CRISPR loci, the RNase P and 7S RNAs, all tRNAs and rRNAs and 69 predicted snoRNAs. Two putative riboswitch RNAs were present in growing but not in stationary phase cells. The procedure used is designed to identify TSS but, assuming that the number of cDNA reads correlates with transcript abundance, the results also provide a semi quantitative documentation of the differences in T. kodakarensis genome expression under different growth conditions and confirm previous observations of substrate-dependent specific gene expression. Many previously unanticipated small RNAs have been identified, some with relative low GC contents (<= 50%) and sequences that do not fold readily into base-paired secondary structures, contrary to the classical expectations for non-coding RNAs in a hyperthermophile. CONCLUSION: The results identify >2,700 TSS, including almost all of the primary sites of transcription initiation upstream of annotated genes, plus many secondary sites, sites within genes and sites resulting in antisense transcripts. The T. kodakarensis genome is small (~2.1 Mbp) and tightly packed with protein encoding genes, but the transcriptomes established also contain many non-coding RNAs and predict extensive RNA-based regulation in this model Archaeon. PMID- 25127549 TI - Effectiveness of screening for abdominal aortic aneurysm during echocardiography. AB - Screening patients with abdominal aortic aneurysm (AAA) is associated with reduced AAA-related mortality, but population screening is poorly implemented. Opportunistic screening during imaging for other indications might be efficient. Single-center series reported AAA rates of 0.8% to 6.5% in patients undergoing transthoracic echocardiography (TTE), with disparities due to selection bias. In this first multicenter study, we aimed to assess the feasibility and criteria for screening AAA during TTE in real-life practice. During a week of May 2011, 79 centers participated in a nationwide survey. All patients aged >=65 years requiring TTE for any indication were eligible, except for those with operated abdominal aorta. We defined AAA by an anteroposterior diameter of the infrarenal aorta>=30 mm. Of 1,382 consecutive patients, abdominal aorta imaging was feasible in 96.7%, with a median delay of 1.7 minutes (>3 minutes in 3.6% of cases). We found AAA in 50 patients (3.7%). Unknown AAA (2.7%) was more frequent in men than women (3.7% vs 1.3%, respectively, p=0.007) and increased by age at 2.2%, 2.5%, and 5.8% in age bands of 65 to 74, 75 to 84, and 85+ years, respectively. None of the female participants aged <75 years had AAA. Smoking status and family history of AAA were significantly more frequent among patients with AAA. The ascending aorta was larger in those with AAA (36.2+/-4.7 vs 34.0+/-5.2 mm, p=0.006), and bicuspid aortic valve and/or major aortic regurgitation were also more frequent (8% vs 2.6%, p=0.017). In conclusion, rapid AAA screening during TTE is feasible and should be limited to men >=65 years and women>=75 years. PMID- 25127551 TI - Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti cholinergic agent against skin injury induced by sulfur mustard. AB - Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal-epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. PMID- 25127552 TI - Australian alcohol policy 2001-2013 and implications for public health. AB - BACKGROUND: Despite a complex and multi-faceted alcohol policy environment in Australia, there are few comprehensive reviews of national and state alcohol policies that assess their effectiveness and research support. In mapping the Australian alcohol policy domain and evaluating policy interventions in each of the core policy areas, this article provides a useful resource for researchers. The implications for protecting public health emanating from this mapping and evaluation of alcohol policy are also discussed. METHODS: This review considered data from: published primary research; alcohol legislation, strategies and alcohol-related press releases for all levels and jurisdictions of Australian government; international publications by prominent non-governmental organisations; and relevant grey literature. These were organised and evaluated using the established framework offered by Thomas Babor and colleagues. RESULTS: Findings indicated great variability in alcohol initiatives across Australia, many of which do not reflect what is currently considered to be evidence-based best practice. CONCLUSIONS: Research showing increasing alcohol-related harms despite steady levels of consumption suggests a need to pursue alcohol policy initiatives that are supported by evidence of harm-reduction. Future initiatives should aim to increase existing alcohol controls in line with suggested best practice in order to protect public health in Australia. PMID- 25127553 TI - Risk factors for diarrhea hospitalization in Bangladesh, 2000-2008: a case-case study of cholera and shigellosis. AB - BACKGROUND: Cholera and shigellosis are endemic on the Indian subcontinent. Our objective was to identify cholera-specific risk factors distinct from shigellosis risk factors. METHODS: We conducted a case-case study among hospitalized diarrheal patients, comparing those with cholera and shigellosis in International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) hospitals in Matlab (rural) and Dhaka (urban) between January 1, 2000 and December 31, 2008. RESULTS: Multivariable Poisson regression models revealed that having more than nine years of education, compared to no education, was associated with a 39% (adjusted Risk Ratio [aRR] = 0.61, 95% confidence interval [CI]: 0.40-0.93) decreased risk for cholera hospitalization in Matlab and a 16% (aRR = 0.84, 95% CI: 0.75-0.94) decreased risk in Dhaka. Having a family member with diarrhea in the past seven days increased cholera hospitalization risk by 17% (aRR = 1.17, 95% CI: 1.09 1.26) in Matlab. CONCLUSIONS: Further studies are needed to elucidate the pathway through which education impacts cholera risk in order to create targeted interventions in cholera-endemic areas. Interventions seeking to reduce transmission and facilitate hygienic practices among family members of index cases with diarrhea should be considered, especially in rural cholera endemic settings. PMID- 25127555 TI - [Reply to authors]. PMID- 25127554 TI - [Self-rated health and educational level in Spain: trends by autonomous communities and gender (2001-2012)]. AB - OBJECTIVE: To identify the trend in self-rated health in Spain by autonomous communities (AC) in the period 2001-2012, as well as differences by gender and age, and the influence of educational level. METHODS: A cross sectional study was carried out using data from the National Health Surveys from 2001 to 2011-12 and the 2009 European Survey. A descriptive analysis was conducted that included gender, age, educational level, and the AC of residence. Logistic regression analyses were developed to explore the temporal trend and the association between educational level and self-rated health. The predictive capacity of the model was calculated using the C statistic. RESULTS: The prevalence of low self-rated health was higher in women with low educational level. Self-rated health improved in women with high educational level (2001:18.6% vs. 2012:14.6%). The highest prevalence of low self-rated health was observed in Andalusia, the Canary Islands, Galicia and Murcia, with differences by gender. Low educational level was associated with low self-rated health in most AC, with good predictive capacity. In all AC except Asturias, low self-rated health was more frequent in women than in men. In Spain, the prevalence of self-rated health showed no variations in the period analyzed and improved in the Balearic Islands, Catalonia, and Madrid. CONCLUSIONS: The prevalence of self-rated health in Spain differed by AC. Although health was unchanged during the period considered, inequalities were found in its temporal trend by educational level and gender, which could lead to an increase in health inequalities in women according educational level. PMID- 25127556 TI - Debonding mechanisms of soft materials at short contact times. AB - A carefully controlled, custom-built adhesion testing device was developed which allows a precise, short dwell time on the order of milliseconds to be applied during a contact adhesion experiment. The dwell time dependence of the adhesive strength of crosslinked poly(dimethylsiloxane) (PDMS) in contact with glass and uncrosslinked styrene butadiene rubber (SBR) in contact with glass and with itself was tested with a spherical probe in a confined Johnson-Kendall-Roberts (JKR) geometry. Analysis of the contact images revealed several unique separation mechanisms which are dependent on dwell time and interfacial properties. PDMS glass interfaces show essentially no dependence of adhesion on the dwell time while the adhesive strength and separation mechanisms of SBR interfaces are shown to vary drastically for dwell times ranging from 40 to 10,000 ms. This influence of dwell time is particularly pronounced for polymer-polymer (SBR-SBR) interfaces. Observations of cavitation due to trapped air pockets in the center of the contact at very short contact times illustrate a transition between a defect-controlled debonding and an interface-controlled debonding which has not been previously reported. PMID- 25127557 TI - Synthesis and characterization of a novel mesoporous silica functionalized with [1,5 bis(di-2-pyridyl)methylene thiocarbohydrazide] and its application as enrichment sorbent for determination of antimony by FI-HG-ETAAS. AB - A simple, sensitive, low-cost and rapid flow injection (FI) on-line sorption preconcentration/hydride generation system has been synchronously coupled to an electrothermal atomic absorption spectrometer (ETAAS) for the determination of trace amounts of Sb in aqueous environmental samples (river and sea water samples). The system is based on retention of the analyte onto a micro-column filled with a novel mesoporous silica functionalised with [1,5 bis(di-2-pyridyl) methylene] thiocarbohydrazide placed in the injection valve of the FI manifold. The adsorption capacity of the resin for Sb was found to be 160.8 umol g(-1). Chemicals and flow variables affecting the continuous preconcentration of antimony, the direct generation of antimony hydride and the final determination of this element by ETAAS were evaluated. The optimized operating conditions selected were: sample pH 5.0, sample flow rate 2.5 ml min(-1), eluent flow rate 5.4 ml min(-1), eluent 2.0% thiourea in 4.0% nitric acid. Under the optimum conditions, the calibration graph obtained was linear over the range 0.025-2.5 MUg L(-1). At a sample frequency of 20 h(-1) and 120 s preconcentration time, the enrichment factor was 22. The detection limit of the method (3o) was 1 ng L(-1) for a 5.0 mL sample volume and the precision was 0.9% (RSD) for 11 replicate determinations at 1.0 MUg L(-1) Sb. The preconcentration factor and detection limit can be improved by increasing the preconcentration time, which can be increased at least up to 5 min. The accuracy of the proposed method was demonstrated by analyzing two certified reference materials and by determining the analyte content in spiked environmental water samples. The results obtained using this method were in good agreement with the certified values of the standard reference materials and the recoveries for the spiked river and sea water samples were 91.3-109.9%. PMID- 25127558 TI - Charge-based characterisation of high-molecular-weight glutenin subunits from common wheat by capillary isoelectric focusing. AB - In this study, the capillary isoelectric focusing (CIEF) method for the separation and charge characterisation of the heterogeneity of high molecular weight-glutenin subunits (HMW-GS) in common wheat (Triticum aestivum L.) using linear polyacrylamide (LPA) and polyvinyl alcohol (PVA) coated capillaries was developed. Particularly good repeatability and well-resolved charge isoform profiles were obtained by introducing a mixture of carrier ampholytes (pH 3-10 and pH 5-8), a high concentration of urea (6M) and SB3-12 as detergent in a sample solution during separation in a PVA-coated capillary. One major and one or two minor isoforms were observed for the individual HMW-GS. These isoforms were satisfactorily separated using a pH gradient into two groups: y-type isoforms and x-type isoforms encoded by the Glu-B1 locus with shorter migration times and remaining x-type isoforms with longer times. The method produced from eight to twelve isoforms of wheat HMW-GS with pI points in the range of 4.72-6.98. Generally, the minor isoforms were more acidic compared with the major isoform. The y-type subunits had an approximately neutral character (pI 6.70-6.98); however, x-types showed a weakly acidic character (pI 4.72-5.23), with the exception of subunits encoded by the Glu-B1 locus. The isoelectric point peak profiles were compared with capillary zone electrophoresis (CZE) electropherograms. Generally, the number of detected isoforms for the particular HMW-GS detected using both methods were similar. PMID- 25127559 TI - Evaluation of immunoglobulins in bovine colostrum using laser induced fluorescence. AB - The objective of the present study was to exploit laser induced fluorescence (LIF) as a spectrochemical analytical technique for evaluation of immunoglobulin (IgG) in bovine colostrum. Colostrum samples were collected from different American Holstein cows at different times after calving. Four samples were gathered from each cow; the first three samples were obtained from the first three milkings (colostrum) and the fourth sample (milk) was obtained a week after calving. It has been demonstrated that LIF can be used as a simple, fast, sensitive and less costly spectrochemical analytical technique for qualitative estimation of IgG in colostrum. LIF results have been confirmed via the quantitative evaluation of IgG in the same samples adopting the single radial immunodiffusion conventional technique and a very good agreement has been obtained. Through LIF it was possible to evaluate bovine colostrum after different milking times and to differentiate qualitatively between colostrum from different animals which may reflect their general health status. A fluorescence linear calibration curve for IgG concentrations from 0 up to 120 g L(-1) has been obtained. In addition, it is feasible to adopt this technique for in situ measurements, i.e. in dairy cattle farms as a simple and fast method for evaluation of IgG in bovine colostrum instead of using lengthy and complicated conventional techniques in laboratories. PMID- 25127560 TI - Quantum dots and p-phenylenediamine based method for the sensitive determination of glucose. AB - By introducing p-phenylenediamine (PPD) to the hybrid system of Mn-doped CdS/ZnS quantum dots (QDs) and glucose oxidase (GOD), a sensitive label-free method was proposed for direct detection of glucose. With glucose and PPD as substrates, 2,5 diamino-N,N'-di-(4-aminophenyl)-2,5-cyclohexadiene-1,4-diimine (DDACD) that intensively quenches the fluorescence of QDs can be produced by the catalysis of GOD. A detection limit as low as 3.2 MUM was obtained with the high-efficient fluorescence quencher. Two linear ranges, from 5.0 MUM to 1000 MUM and from 1.0 mM to 10.0 mM, were identified between time-gated fluorescence intensity and the concentration of glucose. It is shown that the newly proposed methods have high selectivity for glucose over other saccharides and coexisting biological species in serum. The method can be used directly to determine glucose in normal adult human serum without any complicated sample pretreatments. The recovery rate and repeatability of the method were also shown to be satisfactory. PMID- 25127561 TI - A novel electrochemiluminescence tetracyclines sensor based on a Ru(bpy)32+-doped silica nanoparticles/Nafion film modified electrode. AB - A novel method for the determination of tetracyclines (TCs) using electrochemiluminescence (ECL) based on a Ru(bpy)3(2+)-doped silica nanoparticles (RuSiNPs)/Nafion film modified electrode is presented in this paper. The RuSiNPs were prepared by a water-in-oil microemulsion method. The characterization results indicated that the thus-prepared RuSiNPs presented a uniform size of 45 nm and retained the original electrochemical properties of Ru(bpy)3(2+). Importantly, the ECL response on RuSiNPs/Nafion film modified electrode was greatly enhanced by TCs. Under the optimum conditions, the ECL intensity versus the concentration of TCs was found to be linear over the range of 1-100 MUmol L( 1) for tetracycline (TC), 0.1-100 MUmol L(-1) for oxytetracycline (OTC) and 1-100 MUmol L(-1) for chlortetracycline (CTC). The detection limits (S/N=3) were 0.23 MUmol L(-1) for TC, 0.10 MUmol L(-1) for OTC and 0.16 MUmol L(-1) for CTC. Moreover, due to the electrostatic interaction between Ru(bpy)3(2+) and silica matrix, the leaching of Ru(bpy)3(2+) was greatly reduced, therefore, the ECL sensor exhibited excellent repeatability and stability in the detection of TCs. Based on these investigations, the proposed ECL approach was successfully used to analyze the TCs content in drugs. PMID- 25127562 TI - Electronic nose and chiral-capillary electrophoresis in evaluation of the quality changes in commercial green tea leaves during a long-term storage. AB - Electronic nose and capillary electrophoresis were applied in quality control of green tea samples subjected to long-term storage. Twelve representative green teas were considered, available as an "aged" (tea leaves stored during a long term period of two years) and/or "not aged" (fresh products) samples. Their infusions were analyzed by an electronic nose, equipped with an array of six metal oxide semiconductor (MOS) sensors to obtain olfactive fingerprints of the volatile compounds in the infusions headspace. Upon training and chemometric analysis of acquired data (linear discriminant analysis), the electronic nose was found to be able in correctly classifying unknown samples as "aged" or "not aged". Concomitantly, the infusion samples were analyzed by Cyclodextrin-modified Micellar Electrokinetic Chromatography (CD-MEKC) for determination of catechins. The analysis of seven most represented catechins and the methylxanthines theobromine and caffeine revealed a general loss of the polyphenols in each of the considered aged samples (up to 45%, w/w). In addition, the applied enantioselective method based on (2-hydroxypropyl)-beta-cyclodextrin (HP-betaCD) as chiral selector, was exploited for the estimation of (+)-Gallocatechin in the presence of (-)-Gallocatechin; the latter, as the non-native enantiomer, can be associated to the epimerisation of (-)-Epigallocatechin and was assumed as a marker occurring in case of uncorrected storage conditions of tea leaves. Interestingly, it was observed that epimerization did not significantly occur during aging. The application of CD-MEKC and electronic nose allowed for a fast characterization of green teas taking into account that the aroma is a decisive parameter for the acceptance of the product, whereas the catechins content is associated to the biological value. PMID- 25127563 TI - Analytical methods for the determination of DEHP plasticizer alternatives present in medical devices: a review. AB - Until 2010, diethylhexylphthalate (DEHP) was the plasticizer most commonly used to soften PVC medical devices (MDs), because of a good efficiency/cost ratio. In flexible plasticized PVC, phthalates are not chemically bound to PVC and they are released into the environment and thus may come into contact with patients. The European Directive 2007/47/CE, classified DEHP as a product with a toxicity risk and restricted its use in MDs. MD manufacturers were therefore forced to quickly find alternatives to DEHP to maintain the elasticity of PVC nutrition tubings, infusion sets and hemodialysis lines. Several replacement plasticizers, so-called "alternative to DEHP plasticizers" were incorporated into the MDs. Nowadays, the risk of exposure to these compounds for hospitalized patients, particularly in situations classified "at risk", has not yet been evaluated, because migrations studies, providing sufficient exposure and human toxicity data have not been performed. To assess the risk to patients of DEHP plasticizer alternatives, reliable analytical methods must be first developed in order to generate data that supports clinical studies being conducted in this area. After a brief introduction of the characteristics and toxicity of the selected plasticizers used currently in MDs, this review outlines recently analytical methods available to determine and quantify these plasticizers in several matrices, allowing the evaluation of potential risk and so risk management. PMID- 25127564 TI - Metal organic frameworks/macroporous carbon composites with enhanced stability properties and good electrocatalytic ability for ascorbic acid and hemoglobin. AB - The thermal, water and electrochemical stability of Cu-based metal organic frameworks (Cu-MOFs) confined in macroporous carbon (MPC) hybrids has been investigated. Thermogravimetric analyses, X-Ray diffraction, scanning electron microscopy, and cyclic voltammetry were employed to confirm the stability of pure Cu-MOFs, MPC, and Cu-MOFs-MPC. As compared to pure Cu-MOFs, the porous composite materials of MPC and Cu-MOFs interact and seem to form new materials having homogenous structure and chemistry, which show structural stability in aqueous media and electrochemical stability in phosphate buffer solution (PBS pH 7.4). The detection of ascorbic acid and hemoglobin is performed as an electrochemical probe, indicating Cu-MOFs-MPC holds great promise for the design of electrochemical sensors. PMID- 25127565 TI - Detection of copper, lead, cadmium and iron in wine using electronic tongue sensor system. AB - An array of 10 potentiometric chemical sensors has been applied to the detection of total Fe, Cu, Pb and Cd content in digested wine. As digestion of organic matter of wine is necessary prior to the trace metal detection using potentiometric sensors, sample preparation procedures have been optimized. Different variants of wet and microwave digestion and dry ashing, 14 conditions in total, have been tested. Decomposition of organic matter was assessed using Fourier transform mid-infrared spectroscopy and total phenolic content. Dry ashing was found to be the most effective method of wine digestion. Measurements with sensors in individual solutions of Fe(III), Cu(II), Pb(II) and Cd(II) prepared on different backgrounds have shown that their detection limits were below typical concentration levels of these metals in wines and, in the case of Cu, Pb and Cd below maximum allowed concentrations. Detection of Fe in digested wine samples was possible using discrete iron-sensitive sensors with chalcogenide glass membranes with RMSEP of 0.05 mmol L(-1) in the concentration range from 0.0786 to 0.472 mmol L(-1). Low concentration levels of Cu, Pb and Cd in wine and cross-sensitivity of respective sensors resulted in the non-linearity of their responses, requiring back-propagation neural network for the calibration. Calibration models have been calculated using measurements in the model mixed solutions containing all three metals and a set of digested wine sample. RMSEP values for Cu, Pb and Cd were 3.9, 39 and 1.2 MUmol L(-1) in model solutions and 2, 150 and 1 MUmol L(-1) in digested wine samples. PMID- 25127566 TI - A miniaturized capacitively coupled plasma microtorch optical emission spectrometer and a Rh coiled-filament as small-sized electrothermal vaporization device for simultaneous determination of volatile elements from liquid microsamples: spectral and analytical characterization. AB - A low power and low argon consumption (13.56 MHz, 15 W, 150 ml min(-1)) capacitively coupled plasma microtorch interfaced with a low-resolution microspectrometer and a small-sized electrothermal vaporization Rh coiled filament as liquid microsample introduction device into the plasma was investigated for the simultaneous determination of several volatile elements of interest for environment. Constructive details, spectral and analytical characteristics, and optimum operating conditions of the laboratory equipment for the simultaneous determination of Ag, Cd, Cu, Pb and Zn requiring low vaporization power are provided. The method involves drying of 10 MUl sample at 100 degrees C, vaporization at 1500 degrees C and emission measurement by capture of 20 successive spectral episodes each at an integration time of 500 ms. Experiments showed that emission of elements and plasma background were disturbed by the presence of complex matrix and hot Ar flow transporting the microsample into plasma. The emission spectrum of elements is simple, dominated by the resonance lines. The analytical system provided detection limits in the ng ml(-1) range: 0.5(Ag); 1.5(Cd); 5.6(Cu); 20(Pb) and 3(Zn) and absolute detection limits of the order of pg: 5(Ag); 15(Cd); 56(Cu); 200(Pb) and 30(Zn). It was demonstrated the utility and capability of the miniaturized analytical system in the simultaneous determination of elements in soil and water sediment using the standard addition method to compensate for the non-spectral effects of alkali and earth alkaline elements. The analysis of eight certified reference materials exhibited reliable results with recovery in the range of 95-108% and precision of 0.5-9.0% for the five examined elements. The proposed miniaturized analytical system is attractive due to the simple construction of the electrothermal vaporization device and microtorch, low costs associated to plasma generation, high analytical sensitivity and easy-to-run for simultaneous multielemental analysis of liquid microsamples. PMID- 25127567 TI - Evaluation of surface-enhanced Raman scattering detection using a handheld and a bench-top Raman spectrometer: a comparative study. AB - Surface enhanced Raman scattering (SERS) detection using a handheld Raman spectrometer and a bench-top Raman spectrometer was systemically evaluated and compared in this study. Silver dendrites were used as the SERS substrate, and two pesticides, maneb and pyrrolidine dithiocarbamate-ammonium salt (PDCA) were used as the analytes. Capacity and performance were evaluated based on spectral resolution, signal variation, quantitative capacity, sensitivity, flexibility and intelligence for SERS detection. The results showed that the handheld Raman spectrometer had better data consistency, more accurate quantification capacity, as well as the capacity of on-site and intelligence for qualitative and semi quantitative analysis. On the other hand, the bench-top Raman spectrometer showed about 10 times higher sensitivity, as well as flexibility for optimization of the SERS measurements under different parameters such as laser power output, collective time, and objective magnification. The study on the optimization of SERS measurements on a bench-top spectrometer provides a useful guide for designing a handheld Raman spectrometer, specifically for SERS detection. This evaluation can advance the application of a handheld Raman spectrometer for the on-site measurement of trace amounts of pesticides or other chemicals. PMID- 25127568 TI - Non-covalent conjugation of CdTe QDs with lysozyme binding DNA for fluorescent sensing of lysozyme in complex biological sample. AB - Water-soluble cysteamine (CA) capped CdTe quantum dots (QDs) conjugated with lysozyme binding DNA (LBD) was constructed for luminescent sensing of lysozyme by forming a ternary self-assembly complex. Addition of negatively charged lysozyme binding DNA to the positively charged CA capped CdTe QDs buffer solution (Tris HCl pH 7.4) could lead to the formation of QDs-LBD complex through electrostatic interactions. Once lysozyme was introduced into the CdTe QDs-LBD system, it could bind specifically with the QDs-LBD complex, resulting in fluorescence emission enhancement of the QDs due to the surface inert of QDs. At a given amount of LBD and CdTe QDs (LBD: QDs=2: 1), the fluorescence intensity enhancement of QDs was linear with lysozyme concentration over the range of 8.9-71.2 nM, with a detection limit of 4.3 nM. Due to the specific binding of LBD with lysozyme, this approach displayed high selectivity for lysozyme recognition. The sensing mechanism was confirmed by DLS and zeta potential measurement, and agarose gel electrophoresis experiment. Furthermore, the proposed CA-capped CdTe QDs-LBD sensor was applied to lysozyme detection in mouse serum and human morning urine samples, which showed high sensitivity and selectivity in the complex biological sample. PMID- 25127569 TI - A sensitive flow-based procedure for spectrophotometric speciation analysis of inorganic bromine in waters. AB - A flow-based system with solenoid micro-pumps and long path-length spectrophotometry for bromate and bromide determination in drinking water is proposed. The method is based on the formation of an unstable dye from the reaction between bromate, 2-(5-dibromo-2-pyridylazo)-5-(diethylamino)phenol (5-Br PADAP) and thiocyanate ions. A multivariate optimization was carried out. A linear response was observed between 5.0 and 100 ug L(-1) BrO3(-) and the detection limit was estimated as 2.0 ug L(-1) (99.7% confidence level). The coefficient of variation (n=20) and sampling rate were estimated as 1.0% and 40 determinations per hour, respectively. Reagent consumption was estimated as 0.17 ug of 5-Br-PADAP and 230 MUg of NaSCN per measurement, generating 6.0 mL of waste. Bromide determination was carried out after UV-assisted conversion with K2S2O8 using 300 uL of sample within the range 20-400 ug L(-1) Br(-). The generated bromate was then determined by the proposed flow system. The results for tap and commercial mineral water samples agreed with those obtained with the reference procedure at the 95% confidence level. The proposed procedure is therefore a sensitive, environmentally friendly and reliable alternative for inorganic bromine speciation. PMID- 25127570 TI - Construction of an electrochemical sensor based on amino-functionalized metal organic frameworks for differential pulse anodic stripping voltammetric determination of lead. AB - Metal-organic frameworks composite materials have received tremendous attention because of their versatile structures and tunable porosity for various applications. Herein, amino-functionalized metal-organic frameworks (NH2 Cu3(BTC)2; BTC=benzene-1,3,5-tricarboxylate) was prepared and used as a novel electrode modifier for the determination of trace levels of lead. NH2-Cu3(BTC)2 shows quite a good capability for the efficient adsorption of lead from aqueous solutions. The parameters affecting the electrochemical process, such as electrolyte solution pH, the amount of NH2-Cu3(BTC)2 suspension, accumulation potential and accumulation time, were investigated in detail. Under the optimal conditions, the electrochemical sensor exhibited a linear response to the concentration of lead in the range of 1.0*10(-8)-5.0*10(-7) mol L(-1) (R(2)=0.9951) with a detection limit of 5.0*10(-9) mol L(-1). The relative standard deviation of 11 successive scans was 3.10% for 1.0*10(-8) mol L(-1) lead. The method was validated with certified reference material (stream sediment and milk powder) and the analytical results coincided well with the certified values. Furthermore, the method was successfully applied to the determination of target analytes in tap and lake water samples and good recoveries were obtained from different spiked values. PMID- 25127571 TI - Rapid chemiluminescent sandwich enzyme immunoassay capable of consecutively quantifying multiple tumor markers in a sample. AB - Using the role of p-iodophenol in enzyme assay, enhanced 1,1'-oxalyldiimidazole chemiluminescent enzyme immunoassays (ODI-CLEIAs) were developed to consecutively quantify trace levels of triple tumor markers, such as alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate specific antigen (PSA) in a sample. Due to the high sensitivity of enhanced ODI-CLEIAs, it was possible to fix the incubation times (1) to capture a tumor marker with two antibodies, which are primary antibody immobilized on the surface of polystyrene strip-well and detection antibody-conjugated horseradish peroxidase (HRP), and (2) to form resorufin with the addition of substrates (e.g., Amplex Red, H2O2) in order to quantify triple markers in human serum. Enhanced ODI-CLEIAs capable of consecutively and rapidly quantifying triple markers with the same incubation time were more sensitive than conventional enzyme-linked immunosorbent assay (ELISA) capable of separately and slowly quantifying them with different incubation times. In addition, accuracy, precision, and recovery of enhanced ODI CLEIAs in the presence of p-iodophenol were acceptable within statistical error range. PMID- 25127572 TI - Coumarins as turn on/off fluorescent probes for detection of residual acetone in cosmetics following headspace single-drop microextraction. AB - In this work, a new method based on headspace-single drop microextraction for the determination of residual acetone in cosmetics by microfluorospectrometry is proposed. Acetone causes fluorescence changes in a 2.5 uL-ethanolic drop (40% v/v) containing 3.10(-4) mol L(-1) 7-hydroxy-4-methylcoumarin ('turn off') or 6.10(-6) mol L(-1) 7-diethylamino-4-methylcoumarin ('turn on'). Polarity and ability to form hydrogen bonds of short chain alcohols (polar protic solvents) were crucial in order to observe these changes in the presence of acetone (polar aprotic solvent). Parameters related with the HS-SDME procedure were studied, namely headspace volume, composition, volume and temperature of drop, microextraction time, stirring rate, mass and temperature of sample, as well as the effect of potential interferents (alcohols and fragrances). The high volatility of acetone allows its extraction from an untreated cosmetic sample within 3 min. A detection limit of 0.26 ug g(-1) and repeatability, expressed as relative standard deviation, around 5% were reached. Accuracy of the proposed methodology was evaluated by means of recovery studies. The method was successfully used to analyze different cosmetics. Simplicity and high sample throughput can be highlighted. PMID- 25127573 TI - Enzymatic tumour tissue digestion coupled to SPE-UPLC-Tandem Mass Spectrometry as a tool to explore paclitaxel tumour penetration. AB - Paclitaxel is a good compound for regional (intraperitoneal) chemotherapy of peritoneal carcinomatosis. During IPEC, a cytotoxic solution is circulated in the peritoneal cavity, thereby promoting close contact between the cytotoxic agent and the exposed (residual) tumour tissue. To further explore the role of PTX in this type of treatment and study the impact of treatment modalities on tumour tissue penetration, in-vivo animal experiments were set-up. In literature, PTX tumour uptake is frequently studied using autoradiography and/or fluorescence microscopy techniques. Owing to their semi-quantitative nature on one hand and the difficulty of incorporating imaging data within a pharmacokinetic pharmacodynamic modelling framework on the other hand, we set out to develop a validated assay for the quantification of PTX in tumour tissue samples. Furthermore, in order to maximise spatial resolution, care was taken to minimise the sample weight necessary for the analysis. Based on an enzymatic tumour tissue digestion protocol, an easy, less labour-intensive, when compared to mechanical tissue disruption techniques, method was developed. Through validation experiments we showed that our method reliably quantifies PTX in a working range of 30-8000 ng/g tumour tissue. Finally, using samples from the in-vivo experiments we demonstrated the suitability of the developed method. PMID- 25127574 TI - Organo-modified layered double hydroxide-catalyzed Fenton-like ultra-weak chemiluminescence for specific sensing of vitamin B12 in egg yolks. AB - In general, the chemiluminescence (CL) sensing of vitamin B12 is achieved by determining Co(II) liberated from acidified vitamin B12 by a luminol system. However, the luminol system for sensing vitamin B12 has poor selectivity due to serious interference from other metal ions. In this study, as a novel CL amplifier of the Co(II)+H2O2+OH(-) ultra-weak CL reaction (Fenton-like system), dodecylbenzene sulfonate (DBS)-layered double hydroxides (LDHs) have been applied to the specific determination of vitamin B12 by liberating Co(II). The CL intensity increased with increasing the concentration of vitamin B12 in a wide range from 1.0 ng mL(-1) to 5 MUg mL(-1) with a detection limit of 0.57 ng mL(-1) (S/N=3). The proposed method has been successfully applied to determine vitamin B12 in egg yolk with simple procedures, shorter time and higher selectivity. Recoveries from spiked real samples were 96-103%. The results of the proposed method for sensing vitamin B12 in real samples were agreed with those obtained by the standard inductively coupled plasma mass spectrometry (ICP-MS) method. To the best of our knowledge, this is the first report on the CL sensing of vitamin B12 with high selectivity in the absence of luminol. PMID- 25127575 TI - Selective mixed-bed solid phase extraction of atrazine herbicide from environmental water samples using molecularly imprinted polymer. AB - A novel approach for the selective extraction of organic target compounds from water samples has been developed using a mixed-bed solid phase extraction (mixed bed SPE) technique. The molecularly imprinted polymer (MIP) particles are embedded in a network of silica gel to form a stable uniform porous bed. The capabilities of this method are demonstrated using atrazine as a model compound. In comparison to conventional molecularly imprinted-solid phase extraction (MISPE), the proposed mixed-bed MISPE method in combination with gas chromatography-mass spectrometry (GC-MS) analysis enables more reproducible and efficient extraction performance. After optimization of operational parameters (polymerization conditions, bed matrix ingredients, polymer to silica gel ratio, pH of the sample solution, breakthrough volume plus washing and elution conditions), improved LODs (1.34 ug L(-1) in comparison to 2.25 ug L(-1) obtained using MISPE) and limits of quantification (4.5 ug L(-1) for mixed-bed MISPE and 7.5 ug L(-1) for MISPE) were observed for the analysis of atrazine. Furthermore, the relative standard deviations (RSDs) for atrazine at concentrations between 5 and 200 ug L(-1) ranged between 1.8% and 6.3% compared to MISPE (3.5-12.1%). Additionally, the column-to-column reproducibility for the mixed-bed MISPE was significantly improved to 16.1%, compared with 53% that was observed for MISPE. Due to the reduced bed-mass sorbent and at optimized conditions, the total amount of organic solvents required for conditioning, washing and elution steps reduced from more than 25 mL for conventional MISPE to less than 2 mL for mixed-bed MISPE. Besides reduced organic solvent consumption, total sample preparation time of the mixed-bed MISPE method relative to the conventional MISPE was reduced from more than 20 min to less than 10 min. The amount of organic solvent required for complete elution diminished from 3 mL (conventional MISPE) to less than 0.4 mL with the mixed-bed technique shows its inherent potential for online operation with an analytical instrument. In order to evaluate the selectivity and matrix effects of the developed mixed-bed MISPE method, it was applied as an extraction technique for atrazine from environmental wastewater and river water samples. PMID- 25127576 TI - Reversible modulation of gold nanoclusters photoluminescence based on electrochromic poly(methylene blue). AB - Reversible photoluminescence (PL) switches based on a complex of gold nanoclusters and electrochromic poly(methylene blue) (PMB) were realized. The gold nanoclusters PL of hybrid device can be modulated reversibly under electrochemical stimulation. Such an electrochromic device presents several advantages, such as large fluorescence contrast under reduction and oxidation potentials, good reversibility and excellent long-time stability. This simple protocol is anticipated to offer important hints for other nanoclusters and electrochromic materials in the field of photoelectric devices. PMID- 25127577 TI - Evaluation of transformer insulating oil quality using NIR, fluorescence, and NMR spectroscopic data fusion. AB - Power transformers are essential components in electrical energy distribution. One of their most important parts is the insulation system, consisting of Kraft paper immersed in insulating oil. Interfacial tension and color are major parameters used for assessing oil quality and the system's degradation. This work proposes the use of near infrared (NIR), molecular fluorescence, and (1)H nuclear magnetic resonance (NMR) spectroscopy methods combined with chemometric multivariate calibration methods (Partial Least Squares - PLS) to predict interfacial tension and color in insulating mineral oil samples. Interfacial tension and color were also determined using tensiometry and colorimetry as standard reference methods, respectively. The best PLS model was obtained when NIR, fluorescence, and NMR data were combined (data fusion), demonstrating synergy among them. An optimal PLS model was calculated using the selected group of variables according to their importance on PLS projections (VIP). The root mean square errors of prediction (RMSEP) values of 2.9 mN m(-1) and 0.3 were estimated for interfacial tension and color, respectively. Mean relative standard deviations of 1.5% for interfacial tension and 6% for color were registered, meeting quality control requirements set by electrical energy companies. The methods proposed in this work are rapid and simple, showing great advantages over traditional approaches, which are slow and environmentally unfriendly due to chemical waste generation. PMID- 25127578 TI - Electrochemiluminescence on-a-chip: towards a hand-held electrically powered optofluidic source. AB - We report a microfluidic platform that integrates several parallel optical sources based on electrochemiluminescence (ECL) of 9,10-diphenylanthracene (DPA) as luminophore agent. The annihilation of DPA radicals provides a low wavelength emission at lambda=430 nm in the blue-visible range. By varying the distance between electrodes for each ECL integrated source, this glass/PDMS/glass platform enabled a systematic investigation of the main electrochemical parameters involved in ECL. These parameters have been studied either in a static mode or in a dynamic one. Even at slow flow rate (~2 ul s(-1)), the renewal of electroactive species could be easily promoted inside the microfluidic channel which gives rise to a stable optical intensity for several minutes. Compared with traditional optically pumped dye sources, this microfluidic system demonstrates that ECL can be easily implemented on chip for producing much compact optofluidic sources. Such simply electrically powered system-on-chip would surely encourage the future of hand-held uTAS devices with integrated fast detection and embedded electronics. PMID- 25127579 TI - A separation of tyramine on a 2-(4-methoxyphenyl)ethylamine imprinted polymer: an answer from theoretical and experimental studies. AB - A 2-(4-methoxyphenyl)ethylamine imprinted polymer (MIP) was successfully applied for the selective separation of tyramine. A computational analysis was used to predict the affinity of the polymer matrix towards tyramine and a preliminary experimental evaluation was made for the target analyte. Then the experimental analysis of polymer towards tyramine was continued. The binding sites were characterized with employment of the Langmuir and Freudlich models. After the optimization of solid phase extraction towards tyramine, the most appropriate systems for the extraction steps were chosen: methanol-water 85:15 v/v for the loading and the washing as well as 0.04 M aq. ammonium acetate-methanol 30:70 v/v for the elution steps. The biogenic compounds as tryptamine, serotonin, octopamine, synephrine, and l-tyrosine were used for the selectivity study on the basis of binding capacities of the analytes on the imprinted and the non imprinted polymers. The theoretical approach to obtained results allowed to explain the adsorption selectivity of the tested polymer. Finally, the complex matrix of bovine serum albumin was used to show the usefulness of imprinted material for bioanalysis. The obtained recoveries showed the superiority of MIP over the commercial sorbent C18. Total recoveries of tyramine from spiked bovine serum albumin sample were determined as: 95+/-2%, 14+/-3%, and 1.9+/-0.4% for the imprinted, non-imprinted, and commercial C18 sorbents, respectively. PMID- 25127580 TI - Evaluation of internal standardization for the determination of semivolatile analytes in difficult matrices by simultaneous multielement atomic absorption spectrometry. AB - The aim of the present work is to investigate the use of the internal standardization technique combined with permanent chemical modification for the determination of two semivolatile analytes, such as As and Se, in difficult matrices by electrothermal atomic absorption spectrometry. Bismuth and tellurium have been evaluated as internal standards to minimize matrix effects on the direct determination of selenium and arsenic in sediments, by simultaneous electrothermal atomic absorption spectrometry using graphite tubes with integrated platform, pre-treated with different masses of Zr and Ir as permanent modifier. A Perkin-Elmer SIMAA 6000 simultaneous multielement spectrometer was used to study the correlation between two integrated absorbance signals. Matrix effects were evaluated by calculating the slope ratio between the analytical curve obtained from reference solutions prepared in 1.0% (v/v) HNO3 and analytical curve obtained from IS additions in matrix solutions. The results showed that Te was the optimal internal standard and 200 MUg Zr and 20 MUg Ir was the optimal permanent chemical modifier for both analytes. The instrumental limits of detection for As and Se were 1.48 and 1.96 MUg L(-1) without the use of an internal standard and 0.59 and 0.35 MUg L(-1) when Te was used as an internal standard, respectively. Relative standard deviations for a sample with matrix effect containing 100 MUg L(-1) As and 200 MUg L(-1) Se were 1.3% and 2.3% (n=20) using 100 MUg L(-1) Te, respectively, and for a standard solution sample containing 100 MUg L(-1) As and 200 MUg L(-1) Se were 3.0% and 1.2% (n=20) using 100MUgL(-1) Te, respectively. The accuracy of the proposed method was evaluated by an addition-recovery experiment and by the analysis of different certified reference materials. The recovered values were in the 95-100% range for both analytes. PMID- 25127581 TI - GC-MS and FTIR evaluation of the six benzoyl-substituted-1-pentylindoles: isomeric synthetic cannabinoids. AB - This report compares the GC-MS and FTIR properties of all 6 regioisomeric benzoyl substituted-1-n-pentylindoles. These compounds have the benzoyl-group attached at each of the possible ring substituent positions of the indole ring. The six compounds have the same elemental composition C20H21NO yielding identical nominal and exact masses. Additionally, the substituents attached to the indole ring, benzoyl- and 1-n-pentyl-groups, are identical for all six isomers. The electron ionization mass spectra show equivalent regioisomeric major fragments resulting from cleavage of the groups attached to the central indole nucleus. Fragment ions occur at m/z 77 and 105 for the phenyl and benzoyl cations common to all six regioisomeric substances. Fragmentation of the benzoyl and/or pentyl groups yields the cations at m/z 234, 220, 214, 186 and 144. While the relative abundance of the ions varies among the six regioisomeric substances the 1-n pentyl-3-benzoylindole and 1-n-pentyl-5-benzoylindole share very similar relative abundances for the major fragment ions. Chromatographic separations on a capillary column containing a 0.5MUm film of 100% trifluoropropyl methyl polysiloxane (Rtx-200) provided excellent resolution of these six compounds. The elution order appears related to the relative distance between the two indole substituted groups. The latest eluting compounds (highest retention time) have the two substituents on opposite sides of the indole nucleus. Infrared absorption spectral data show the carbonyl absorption band for each of the benzoylindoles and provide distinguishing and characteristic information to individualize each of the regioisomers in this set of compounds. PMID- 25127582 TI - Multiple headspace solid-phase microextraction for quantifying volatile free fatty acids in cheeses. AB - Multiple headspace solid-phase microextraction (MHS-SPME) has been utilized for the quantitative determination of 9 volatile free fatty acids (FFAs) in cheeses, in combination with gas-chromatography and flame-ionization detection (GC-FID). Variables affecting HS-SPME and MHS-SPME were optimized to attain adequate sensitivity while allowing correct application of the MHS method. Thus, the MHS SPME method was successfully performed when using 0.3g of cheese and 1 mL of NaCl (sat. solution), which is subjected to four consecutive extractions using the carboxen-polydimethylsyloxane (CAR-PDMS) as the commercial SPME coating, 40 min of HS extraction time at 45 degrees C, and 6 min of desorption time in the GC injector at 290 degrees C. The MHS-SPME permitted the calculation of beta values, which range from 0.72+/-0.01-0.95+/-0.02, depending on the cheese studied. Later, this beta parameter is used to perform quantitation for the 9 volatile FFAs after just a single HS-SPME extraction, using an external solvent calibration curve. The validity of the utilization of an external solvent calibration was tested with aqueous standards of volatile FFAs, getting average recoveries higher than 81.2%. Quantitation by MHS-SPME was free of matrix interferences despite measuring a complex cheese sample. The optimized method was validated, presenting inter-day reproducibility values (as RSD in %) lower than 13%, and limits of detection down to 7 ug kg(-1). The method was also compared with a conventional extraction method such as solid-phase extraction for the studied cheeses elaborated with goat milk, generating comparable results. To our knowledge, this is the first time that MHS-SPME has been applied to volatiles in cheeses. PMID- 25127583 TI - Novel miniaturized sensors for potentiometric batch and flow-injection analysis (FIA) of perchlorate in fireworks and propellants. AB - Three planar miniaturized perchlorate membrane sensors (3*5 mm(2)) are prepared using a flexible Kaptan substrate coated with nitron-perchlorate (NT-ClO4) [sensor 1], methylene blue-perchlorate (MB-ClO4) [sensor II] and indium-porphyrin (In-Por) [sensor III] as electroactive materials in PVC membranes plasticized with 2-NPPE. Sensors I, II and III display near-Nernstian response for 1.0*10(-5) 1.0*10(-2), 3.1*10(-5)-1.0*10(-2) and 3.1*10(-6)-1.0*10(-2) mol L(-1) ClO4(-) with lower detection limits of 6.1*10(-6), 6.9*10(-6) and 1.2*10(-6) mol L(-1), and anionic calibration slopes of 50.9+/-0.4, 48.4+/-0.4 and 57.7+/-0.3 mV decade(-1), respectively. Methods for determining perchlorate using these sensors offer many attractive advantages including simplicity, flexibility, cost effectiveness, wide linear dynamic response range (0.1-1000 ppm), low detection limit (<1.2*10(-6) mol L(-1)=0.1 ppm), small sample test volume (100 MUL), safety, short response time (<20 s), long life span (~8 weeks), and extended wide working pH range (4.5-8.0). The sensors show high selectivity in the presence of some inorganic ions (e.g., PO4(3-), SO4(2-), S2O3(2-), NO2(-), NO3(-), N3(-), CN( ), Cl(-), Br(-), I(-)) and automation feasibility. Indium-porphyrin based membrane sensor (sensor III) is used as a detector in a wall-jet flow injection set-up to enable accurate flow injection analysis (FIA) of perchlorate in some fireworks without interferences from the associated reducing agents (sulfur and charcoal), binders (dextrin, lactose), coloring agents (calcium, strontium, copper, iron, sodium), color brighten (linseed oil) and regulators (aluminum flakes) which are commonly used in the formulations. The sensor is also used for perchlorate assessment in some propellant powders. The results fairly agree with data obtained by ion-chromatography. PMID- 25127584 TI - Ratiometric fluorescent probe for biothiol in aqueous medium with fluorescent organic nanoparticles. AB - A dipodal rhodamine-based mercury complex have been designed and synthesized, for the selective detection of 3-mercaptopropionic acid (MPA). To avoid the poor solubility of rhodamine-based ligand in pure water, the Hg(2+) complex of fluorescent organic nanoparticles (FONs) of ligand have been developed using reprecipitation method and the formation of 1:1 complex has been confirmed with various spectroscopic techniques. The resultant chemosensor can detect MPA in a concentration range of 60 nM-1 MUM (in buffered aqueous medium) with detection limit of 60 nM. PMID- 25127585 TI - An in-needle extraction technique in determination of organic compounds released from dental tissue conditioners incubated in artificial saliva. AB - The use of an in-needle technique for direct isolation of analytes from real liquid samples is a new proposal. The in-needle technique has been relatively seldom used for direct sampling of liquid matrix through the needle. In this work the in-needle technique has been applied for the determination of compounds evolved to artificial saliva from dental prosthetic materials. It has been shown that results from the experiment with in-needle device were at least comparable with those obtained with using well known solid phase extraction (SPE). It is worth to mention that in-needle extraction offers some advantages: lower consumption of solvent, shorter step-preparation time and reduced costs. The compounds released from prosthetic materials may affect the stability of tissue conditioners and limit their long-term use in the oral cavity. Examined soft dental materials have been found to be stable as minor amount of various species have been emitted from them. Results of the stability tests of soft dental materials with the use of in-needle device on sample preparation step enable their quick evaluation and estimations of their quality. PMID- 25127586 TI - A multiclass method for the analysis of endocrine disrupting chemicals in human urine samples. Sample treatment by dispersive liquid-liquid microextraction. AB - The population is continuously exposed to endocrine disrupting chemicals (EDCs). This has influenced an increase in diseases and syndromes that are more frequent nowadays. Therefore, it is necessary to develop new analytical procedures to evaluate the exposure with the ultimate objective of establishing, in an accurate way, relationships between EDCs and harmful health effects. In the present work, a new method based on a sample treatment by dispersive liquid-liquid microextraction (DLLME) for the extraction of six parabens (methyl-, ethyl-, isopropyl-, propyl-, isobutyl and butylparaben), six benzophenones (benzophenone 1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8 and 4 hydroxybenzophenone) and two bisphenols (bisphenol A and bisphenol S) in human urine samples, followed by gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis is proposed. An enzymatic treatment allows determining the total content of the target EDCs. The extraction parameters were accurately optimized using multivariate optimization strategies. Ethylparaben ring-(13)C6 and bisphenol A d16 were used as surrogates. Found limits of quantification ranging from 0.2 to 0.5 ng mL(-1) and inter-day variability (evaluated as relative standard deviation) ranging from 2.0% to 14.9%. The method was validated using matrix matched standard calibration followed by a recovery assay with spiked samples. Recovery rates ranged from 94% to 105%. A good linearity, for concentrations up to 300 ng mL(-1) for parabens and 40 ng mL(-1) for benzophenones and bisphenols, respectively, was obtained. The method was satisfactorily applied for the determination of target compounds in human urine samples from 20 randomly selected individuals. PMID- 25127587 TI - Ultrasensitive electrochemiluminescent detection of cardiac troponin I based on a self-enhanced Ru(II) complex. AB - To promote the luminous efficiency of luminophore, traditional electrochemiluminescence (ECL) immunoassay usually adopts the adding of coreactant into testing solution. However, many adverse micro-environmental factors in the solution are a limiting factor in ECL analytical techniques and received extensive attention. In our work, a self-enhanced ECL luminophore was synthesized by combining the coreactant (l-cysteine) and the luminophor (tris (4,4'-dicarboxylicacid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)3(2+))) to form one Ru(II) complex and was applied to fabricate a reagentless immunosensor for the detection of cardiac troponin I (cTnI) for the first time. Herein gold nanorods (AuNRs), due to their high specific surface area and good electrocatalytic ability, were used as carriers for the immobilization of Ru(II) complex and cTnI antibody to obtain the Ab2 bioconjugates as signal labels. The application of the self-enhanced Ru(II) complex not only avoided the addition of any coreactant into testing solution for simplifying the operation, but also achieved the intramolecular reaction for improving the ECL signal due to shorter electron transfer path and less energy loss. In view of these advantages, the proposed immunosensor achieved a wide linear range from 0.25 pg/mL to 0.1 ng/mL with an impressive detection limit of 0.083 pg/mL for cTnI (S/N=3). PMID- 25127588 TI - A sensitive and selective colorimetric method for detection of copper ions based on anti-aggregation of unmodified gold nanoparticles. AB - A highly sensitive and selective colorimetric method for detection of copper ions, based on anti-aggregation of D-penicillamine (D-PC) induced aggregated gold nanoparticles (AuNPs) was developed. Copper ions can hinder the aggregation of AuNPs induced by D-PC, through formation of mixed-valence complex with D-PC that is a selective copper chelator. In the presence of a fixed amount of D-PC, the aggregation of AuNPs decreases with increasing concentrations of Cu(2+) along with a color change from blue to red in AuNPs solution and an increase in the absorption ratio (A520/A650). Under the optimum experimental conditions (pH 7, [AuNPs] =3.0 nmol L(-1) and [NaCl]=25 mmol L(-1)), a linear calibration curve for Cu(2+) was obtained within the range of 0.05-1.85 umol L(-1) with a limit of detection (3Sb) of 30 nmol L(-1). Excellent selectivity toward Cu(2+) was observed among various metal ions due to a specific complex formation between Cu(2+) and D-PC. The proposed method has been successfully applied for the detection of Cu(2+) in various real samples. PMID- 25127589 TI - Application of a fully integrated photodegradation-detection flow-batch analysis system with an on-line preconcentration step for the determination of metsulfuron methyl in water samples. AB - This work presents the development of a fully automated flow-batch analysis (FBA) system as a new approach for on-line preconcentration, photodegradation and fluorescence detection in a lab-constructed mixing chamber that was designed to perform these processes without sample dispersion. The system positions the mixing chamber into the detection system and varies the instrumental parameters according to the required photodegradation conditions. The developed FBA system is simple and easily coupled with any sample pretreatment without altering the configuration. This FBA system was implemented to photodegrade and determine the fluorescence of the degradation products of metsulfuron methyl (MSM), a naturally non-fluorescent herbicide of the sulfonylurea's family. An on-line solid phase extraction (SPE) and clean up procedure using a C18 minicolumn was coupled to the photodegradation-detection mixing chamber (PDMC) that was located in the spectrofluorometer. An enrichment factor of 27 was achieved. Photodegradation conditions have been optimized by considering the influence of the elution solvent on both the formation of the photoproduct and on the fluorescence signal. Under optimal conditions, the calibration for the MSM determination was linear over the range of 1.00-7.20 ug L(-1). The limit of detection (LOD) was 0.28 ug L( 1); the relative standard deviation was 2.0% and the sample throughput for the entire process was 3h(-1). The proposed method was applied to real water samples from the Bahia Blanca's agricultural region (Bahia Blanca, Buenos Aires, Argentina). This method obtained satisfactory recoveries with a range of 94.7 109.8%. PMID- 25127590 TI - A two-photon ratiometric fluorescent probe enables spatial coordinates determination of intracellular pH. AB - We reported a two-photon ratiometric fluorescent probe for detecting intracellular pH. When excited with 800 nm laser, an optimal output of laser as the routine equipment of two-photon fluorescence microscopy, the two-photon excited fluorescence of this probe showed distinct emission peak shift as large as 109 nm upon the change of pH values in vitro. Very importantly, the experiment results show that this probe has large two-photon absorption cross-section at pH 4.5 at 800 nm of 354 g, which ranks it as one of the best two-photon ratiometric fluorescent pH probes, and its working pH value is between 4.0 and 8.0 which could fit the intracellular pH range. Moreover, utilizing this probe, the two photon ratiometric fluorescent images in living cells have been obtained, and the spatial coordinates of intracellular pH can be mapped. At the same time, the probe also exhibited selectivity, photostability and membrane permeability. And the photophysical properties of this probe in various solvents indicated that these photophysical properties variations are due to an intramolecular charge transfer process. At last, the imaging depth of the probe in liver biopsy slices was investigated. The experimental results demonstrated the maximum imaging depth can arrive 66 um in living rat liver tissues. PMID- 25127591 TI - Highly sensitive fluorescence quantitative detection of specific DNA sequences with molecular beacons and nucleic acid dye SYBR Green I. AB - A highly sensitive fluorescence method of quantitative detection for specific DNA sequence is developed based on molecular beacon (MB) and nucleic acid dye SYBR Green I by synchronous fluorescence analysis. It is demonstrated by an oligonucleotide sequence of wild-type HBV (target DNA) as a model system. In this strategy, the fluorophore of MB is designed to be 6-carboxyfluorescein group (FAM), and the maximum excitation wavelength and maximum emission wavelength are both very close to that of SYBR Green I. In the presence of targets DNA, the MBs hybridize with the targets DNA and form double-strand DNA (dsDNA), the fluorophore FAM is separated from the quencher BHQ-1, thus the fluorophore emit fluorescence. At the same time, SYBR Green I binds to dsDNA, the fluorescence intensity of SYBR Green I is significantly enhanced. When targets DNA are detected by synchronous fluorescence analysis, the fluorescence peaks of FAM and SYBR Green I overlap completely, so the fluorescence signal of system will be significantly enhanced. Thus, highly sensitive fluorescence quantitative detection for DNA can be realized. Under the optimum conditions, the total fluorescence intensity of FAM and SYBR Green I exhibits good linear dependence on concentration of targets DNA in the range from 2*10(-11) to 2.5*10(-9)M. The detection limit of target DNA is estimated to be 9*10(-12)M (3sigma). Compared with previously reported methods of detection DNA with MB, the proposed method can significantly enhance the detection sensitivity. PMID- 25127592 TI - Generation of volatile copper species after in situ ionic liquid formation dispersive liquid-liquid microextraction prior to atomic absorption spectrometric detection. AB - The new procedure using in situ synthesis of ionic liquid extractant for dispersive liquid-liquid microextraction (in situ IL DLLME) combined with generation of volatile species prior to electrothermal atomic absorption spectrometry (ET AAS) for the determination of copper in soil samples was developed. Analytical signals were obtained without the back-extraction of copper from the IL phase prior to its determination. Under optimal conditions, the extraction in 10 mL of sample solution employing 8 MUL of 1-hexyl-3 methylimidazolium bis[(trifluoromethyl)sulfonyl]imide (HmimNTf2) (as the extraction solvent) was conducted. The ionic liquid served as two-task reagent: the efficient extractant and enhancement substance for generation step. The chemical generation of volatile species was performed by reduction of acidified copper solution (HCl 0.8 mol L(-1)) with NaBH4 (1.5%). Some essential parameters of the chemical generation such as NaBH4 and HCl concentrations, the kind and concentration of ionic liquid, carrier gas (Ar) flow rate, reaction and trapping time as well as pyrolysis and atomization temperatures were studied. For photogeneration the effect of the parameters such as the kind and concentration of low molecular weight organic acids and ionic liquid, carrier gas (Ar) flow rate, UV irradiation and ultrasonication time on the analytical signals were studied. The detection limit was found as 1.8 ng mL(-1) and the relative standard deviation (RSD) for seven replicate measurements of 100 ug mL(-1) in sample solution was 7%. The accuracy of the proposed method was evaluated by analysis of the certified reference materials. The measured copper contents in the reference materials were in satisfactory agreement with the certified values. The method was successfully applied to analysis of the soil and sediment samples. PMID- 25127593 TI - Photochemical sample treatment: a greener approach to chlorobenzene determination in sediments. AB - Due to worker's exposure, solvent and stationary phases' consumption, sample purification is one of the most polluting steps in analytical procedures for determination of organic pollutants in real samples. The use of photochemical sample treatment represents a valid alternative methodology for extracts clean up allowing for a reduction of the used amount of organic solvents. In this paper we report the first application on the photolytic destruction of organic substances to eliminate some of the interferences in the analysis of Chlorobenzenes in sediment samples. The method's efficiency and robustness were compared with classic silica column purification process currently used in clean up procedures in sediment analysis. Quality parameters such as recovery, linearity and reproducibility were studied. The entire procedure was validated by three replicate analysis of spiked real sediment sample. The quantification limits (LOQ) obtained by us ranged from 1.0 to 2.3 ng g(-1), while the detection limits (LOD) were of 1.0 ng g(-1). The RSD for each congener was below 10% and recoveries were in the range 95-130%. Results based on the analysis of real samples showed similar or improved detection thresholds and pointed out the advantages of the photochemical methodology in terms of costs, use of chemical substances and operator's safety according to Green Analytical Chemistry principles. PMID- 25127594 TI - A novel sulfate-reducing bacteria detection method based on inhibition of cysteine protease activity. AB - Sulfate-reducing bacteria (SRB) have been extensively studied in corrosion and environmental science. However, fast enumeration of SRB population is still a difficult task. This work presents a novel specific SRB detection method based on inhibition of cysteine protease activity. The hydrolytic activity of cysteine protease was inhibited by taking advantage of sulfide, the characteristic metabolic product of SRB, to attack active cysteine thiol group in cysteine protease catalytic sites. The active thiol S-sulfhydration process could be used for SRB detection, since the amount of sulfide accumulated in culture medium was highly related with initial bacterial concentration. The working conditions of cysteine protease have been optimized to obtain better detection capability, and the SRB detection performances have been evaluated in this work. The proposed SRB detection method based on inhibition of cysteine protease activity avoided the use of biological recognition elements. In addition, compared with the widely used most probable number (MPN) method which would take up to at least 15days to accomplish whole detection process, the method based on inhibition of papain activity could detect SRB in 2 days, with a detection limit of 5.21*10(2) cfu mL( 1). The detection time for SRB population quantitative analysis was greatly shortened. PMID- 25127595 TI - Glucose biosensor based on multisegment nanowires exhibiting reversible magnetic control. AB - We describe the amperometric detection of glucose using oriented nanowires with magnetic switching of the bioelectrochemical process. The fabrication process of the nanowires was prepared through controlled nucleation and growth during a stepwise electrochemical deposition, and it was characterized using scanning electron microscopy. Cyclic voltammetry and amperometry were used to study the magnetoswitchable property; this control was accomplished by changing the surface orientation of nanowires. Under the optimal condition, the amperometric response was also linear up to a glucose concentration of 0.1-16.0 mmol L(-1) with a sensitivity of 81 MUA mM(-1). The detection limit was estimated for 4.8*10(-8) mol L(-1), defined from a signal/noise ratio of 3. It also exhibits good reproducibility and high selectivity with insignificant interference from ascorbic acid, acetoaminophen, and uric acid. The resulting biosensor was applied to detect the blood sugar in human serum samples without any pretreatment, and the results were comparatively in agreement with the clinical assay. PMID- 25127596 TI - Development of aptamer-conjugated magnetic graphene/gold nanoparticle hybrid nanocomposites for specific enrichment and rapid analysis of thrombin by MALDI TOF MS. AB - Simple, rapid and sensitive analysis of thrombin (a tumor biomarker) in complex samples is quite clinical relevant and essential for the development of disease diagnosis and pharmacotherapy. Herein, we developed a novel method based on aptamer-conjugated magnetic graphene/gold nanoparticles nanocomposites (MagG@Au) for specific enrichment and rapid analysis of thrombin in biological samples using MALDI-TOF-MS. At first, gold nanoparticles were compactly deposited on PDDA functionalized magnetic graphene through electrostatic interaction. Afterwards, aptamer was easily conjugated to gold nanoparticles via Au-S bond formation. The as-made aptamer-conjugated nanocomposites took advantage of the magnetism of magnetic graphene, the high affinity and specificity of aptamer, facilitating a high-efficient separation and enrichment of thrombin. More importantly, due to the large surface area of the hybrid substrate, the average coverage density of aptamer achieved 0.34 nmol/mg, which enhanced the thrombin binding capacity and the recovery of thrombin in real samples. In turn, the enriched thrombin attributed to the sensitive output of MALDI-TOF mass spectrometry signal, 0.085 ng MUL(-1) (2.36 nM) thrombin could be detected. This proposed method has a relatively wide linear relation ranging from 0.1 ng MUL(-1) to 10 ng MUL(-1), and satisfactory specificity. The proposed high-throughput method based on MALDI-TOF MS is expected to the application in the disease biomarker detection and clinical diagnosis. PMID- 25127597 TI - Development of microwave-assisted acid hydrolysis of proteins using a commercial microwave reactor and its combination with LC-MS for protein full-sequence analysis. AB - Microwave-assisted acid hydrolysis (MAAH) can be used to degrade a protein non specifically into many peptides with overlapping sequences which can be identified by mass spectrometry (MS) to produce a sequence map that covers the full sequence of a protein. The success of this method for protein sequence analysis depends on the proper control of the MAAH process, which is currently done using a household microwave oven. However, to meet the regulatory or good laboratory practice (GLP) requirement in a clinical or pharmaceutical laboratory, using a commercial microwave device is often required. In this paper, we report a method of performing MAAH using a CEM Discover single-mode microwave reactor. It is shown that, using an optimized protocol for MAAH, reproducible results comparable to those obtained using a household microwave oven can be generated using the commercial reactor. To illustrate the potential applications of MAAH MS for characterizing clinically relevant proteins, this method was applied, for the first time, to map the amino acid sequences of normal and sickle-cell human hemoglobin as well as bovine hemoglobin. Full sequence coverage was readily achieved from 294 and 266 unique peptides matched to the alpha and beta subunits of normal hemoglobin, respectively, 334 and 265 unique peptides matched to the alpha and beta submit units of sickle-cell hemoglobin, and 377 and 224 unique peptides matched to the alpha and beta subunits of bovine hemoglobin. This method opens the possibility for any laboratory to use a commercial laboratory equipment to perform MAAH MS for protein full-sequence analysis. PMID- 25127598 TI - A cross-reactive sensor array for the fluorescence qualitative analysis of heavy metal ions. AB - A cross-reactive sensor array using mercaptopropionic acid modified cadmium telluride (CdTe), glutathione modified CdTe, poly(methacrylic acid) modified silver nanoclusters, bovine serum albumin modified gold nanoclusters, rhodamine derivative and calcein blue as fluorescent indicators has been designed for the detection of seven heavy metal ions (Ag(+), Hg(2+), Pb(2+), Cu(2+), Cr(3+), Mn(2+) and Cd(2+)). The discriminatory capacity of the sensor array to different heavy metal ions in different pH solutions has been tested and the results have been analyzed with linear discriminant analysis. Results showed that the sensor array could be used to qualitatively analyze the selected heavy metal ions. The array performance was also evaluated in the identification of known and unknown samples and the preliminary results suggested the promising practicability of the designed sensor assay. PMID- 25127599 TI - Assessment of robustness on analysis using headspace solid-phase microextraction and comprehensive two-dimensional gas chromatography through experimental designs. AB - Plackett-Burman experimental design was applied for the robustness assessment of GC*GC-qMS (Comprehensive Two-Dimensional Gas Chromatography with Fast Quadrupolar Mass Spectrometric Detection) in quantitative and qualitative analysis of volatiles compounds from chocolate samples isolated by headspace solid-phase microextraction (HS-SPME). The influence of small changes around the nominal level of six factors deemed as important on peak areas (carrier gas flow rate, modulation period, temperature of ionic source, MS photomultiplier power, injector temperature and interface temperature) and of four factors considered as potentially influential on spectral quality (minimum and maximum limits of the scanned mass ranges, ions source temperature and photomultiplier power). The analytes selected for the study were 2,3,5-trimethylpyrazine, 2-octanone, octanal, 2-pentyl-furan, 2,3,5,6-tetramethylpyrazine, and 2-nonanone e nonanal. The factors pointed out as important on the robustness of the system were photomultiplier power for quantitative analysis and lower limit of mass scanning range for qualitative analysis. PMID- 25127600 TI - Continuous sample drop flow-based microextraction method as a microextraction technique for determination of organic compounds in water sample. AB - Continuous sample drop flow-based microextraction (CSDF-ME) is an improved version of continuous-flow microextraction (CFME) and a novel technique developed for extraction and preconcentration of benzene, toluene, ethyl benzene, m-xylene and o-xylene (BTEXs) from aqueous samples prior to gas chromatography-flame ionization detection (GC-FID). In this technique, a small amount (a few microliters) of organic solvent is transferred to the bottom of a conical bottom test tube and a few mL of aqueous solution is moved through the organic solvent at relatively slow flow rate. The aqueous solution transforms into fine droplets while passing through the organic solvent. After extraction, the enriched analyte in the extraction solvent is determined by GC-FID. The type of extraction solvent, its volume, needle diameter, and aqueous sample flow rate were investigated. The enrichment factor was 221-269 under optimum conditions and the recovery was 89-102%. The linear ranges and limits of detection for BTEXs were 2 500 and 1.4-3.1 ug L(-1), respectively. The relative standard deviations for 10 ug L(-1) of BTEXs in water were 1.8-6.2% (n=5). The advantages of CSDF-ME are its low cost, relatively short sample preparation time, low solvent consumption, high recovery, and high enrichment factor. PMID- 25127601 TI - Cytochrome P450 2D6 based electrochemical sensor for the determination of codeine. AB - Considering the enzymatic activity of the cytochrome P450 2D6 on substrates such as codeine, the current paper includes the development of an enzymatic biosensor for detection of this drug. Home-made screen-printed electrodes were used as electrochemical transducers of the biosensor, in which the enzyme was covalently attached to the carbon surface of the working electrode, this type of modification being the most suitable for the immobilization of the biological element. Chronoamperometric measurements were carried out under optimum conditions of pH and working potential, pH 7 and +200 mV vs. screen-printed Ag/AgCl electrode, giving a reduction signal related to the concentration of codeine in solution. Consecutive additions of a solution of codeine were performed to obtain calibration curves in order to validate the electrochemical method in terms of precision and calculate its capability of detection. These biosensors were used for the determination of codeine in urine and commercial pharmaceutical samples. PMID- 25127602 TI - Radical scavenging activity of antioxidants evaluated by means of electrogenerated HO radical. AB - A method is proposed and tested concerning the characterization of antioxidants by means of their reaction with electrogenerated HO radicals in galvanostatic assays with simultaneous O2 evolution, using a Pt anode fairly oxidized. The consumption of a set of species with antioxidant activity, ascorbic acid (AA), caffeic acid (CA), gallic acid (GA) and trolox (T), is described by a first order kinetics. The rate of the processes is limited by the kinetics of reaction with HO radicals and by the kinetics of charge transfer. Information regarding the scavenger activity of antioxidants is obtained by the relative value of the rate constant of the reaction between antioxidants and HO radicals, k(AO,HO)/k(O2). The number of HO radicals scavenged per molecule of antioxidant is also estimated and ranged from 260 (ascorbic acid) to 500 (gallic acid). The method is applied successfully in the characterization of the scavenger activity of ascorbic acid in a green-tea based beverage. PMID- 25127604 TI - Towards a non-invasive quantitative analysis of the organic components in museum objects varnishes by vibrational spectroscopies: methodological approach. AB - The compositions of ancient varnishes are mainly determined destructively by separation methods coupled to mass spectrometry. In this study, a methodology for non-invasive quantitative analyses of varnishes by vibrational spectroscopies is proposed. For that, experimental simplified varnishes of colophony and linseed oil were prepared according to 18th century traditional recipes with an increasing mass concentration ratio of colophony/linseed oil. FT-Raman and IR analyses using ATR and non-invasive reflectance modes were done on the "pure" materials and on the different mixtures. Then, a new approach involving spectral decomposition calculation was developed considering the mixture spectra as a linear combination of the pure materials ones, and giving a relative amount of each component. Specific spectral regions were treated and the obtained results show a good accuracy between the prepared and calculated amounts of the two compounds. We were thus able to detect and quantify from 10% to 50% of colophony in linseed oil using non-invasive techniques that can also be conducted in situ with portable instruments when it comes to museum varnished objects and artifacts. PMID- 25127603 TI - Amplified electrochemical detection of protein kinase activity based on gold nanoparticles/multi-walled carbon nanotubes nanohybrids. AB - A sensitive and simple electrochemical strategy has been developed for assay of protein kinase A (PKA) activity and inhibition using gold nanoparticles/multi walled carbon nanotubes (AuNPs/MWNTs) nanohybrids. Key features of this assay included intrinsic peroxidase-like activity of positively-charged gold nanoparticles (+AuNPs) and signal transduction and amplification of multi-walled carbon nanotubes (MWNTs). In this assay, an N-terminally cysteine-containing peptide was self-assembled onto the gold electrode via Au-S bonding and used as substrate for PKA, and adenosine-5'-(gamma-thio)-triphosphate was used as co substrate. Upon thiophosphorylation in the presence of PKA, the AuNPs/MWNTs nanohybrids would be fixed onto the peptides via Au-S bond. The conjugated AuNPs/MWNTs nanohybrids could catalyze the 3, 3', 5, 5'-Tetramethylbenzidine (TMB) oxidation by H2O2 to form TMB oxidation product, which was reduced at the electrode surface to generate an electrochemical current. It was eT on state. The current signal intensity is proportional to the activity of PKA. Here, the presence of MWNTs not only increased the surface area for accumulation of +AuNPs but also could promote electron-transfer reaction. It was found that the electrochemical strategy can be employed to assay PKA activity with a low detection limit of 0.09 U/mL. The linear range of the assay for PKA enzymatic unit/ml was 0.1-1 U/mL. Furthermore, the interferences experiments of T4 polynucleotide kinase (T4 PNK) and Casein kinase II (CK2), and inhibition of PKA, have also been studied by using this strategy. The developed method would provide a diversified platform for kinase activity and inhibition monitoring. PMID- 25127605 TI - A new voltammetric sensor for sensitive and selective determination of xanthine based on DNA and polyaniline composite Langmuir-Blodgett film. AB - DNA-polyaniline (PAn) complex Langmuir-Blodgett film modified glassy carbon electrode (GCE) was used as a new voltammetric sensor (DNA/PAn-LB/GCE) for xanthine (XA) detection. The characteristic of DNA/PAn-LB film was studied by electrochemical impedance spectroscopy and scanning electron microscope. Electrochemical behaviors of XA at the sensor were studied in pH 7.0 phosphate buffer solutions by cyclic voltammetry and differential pulse anodic voltammetry. The results showed that this new modified electrode exhibited an excellent immunity from uric acid and hypoxanthine interference and a new sensitive and selective electroanalytical method for XA was proposed with wider linear range. Under the optimum conditions, the calibration curve for XA was obtained over the range of 7.0*10(-8)-1.0*10(-5) mol L(-1), with the detection limit of 3.0*10(-8) mol L(-1). The practicability of this method was demonstrated by determining the concentration of XA in human serum samples. PMID- 25127606 TI - Development, optimization and validation of a multimethod for the determination of 36 mycotoxins in wines by liquid chromatography-tandem mass spectrometry. AB - A fast and efficient multimethod for the determination of 36 mycotoxins in wine, using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC MS/MS), was developed, optimized, validated and implemented in routine analysis. A simplified, quick extraction was performed with acetonitrile, derived from the QuEChERS (quick, easy, cheap, effective, rugged and safe) approach, which was traditionally developed for pesticides analysis. This study aimed at a single extraction and chromatographic separation for 36 mycotoxins. Optimization tests were performed to find the proper ratio of wine: water and extraction solvent and the need for an additional buffering step with ammonium formate/formic acid and a dispersive SPE cleanup with various sorbents. The dSPE steps did not show significant improvement in analysis results, therefore, it was not applied in the final method to be validated. The mycotoxins were separated and detected on a UPLC-MS/MS system, used in the ESI positive ionization mode. The various mycotoxins were divided in three different concentration level groups, according to their sensitivity in UPLC-MS/MS. The validation was performed by analyzing recovery samples at three different spike levels with six replicates (n=6) at each level. Linearity (r(2)) of calibration curves, accuracy (recovery %), instrument limits of detection and method limits of quantification (LOD and LOQ), precision (RSD%) and matrix effects (%) were determined for each individual mycotoxin. From the 36 mycotoxins analyzed by UPLC-MS/MS (ESI+), 35 showed average recoveries in the range 70-120%, and 86% of these with a RSD<=20% at the lowest spike level (for Group I, II and III, respectively, 1, 50 and 10 ug kg( 1)). The higher spike levels showed even better results. Only nivalenol could not be quantified at any concentration level. The method LOQ for 86% of the mycotoxins studied was the lowest spike level tested. The matrix effect observed was low for most mycotoxins analyzed and had no significant influence on the analytical results obtained. The developed procedure was applied successfully in routine analysis in a survey of wine samples originating from different countries. PMID- 25127607 TI - The QuEChERS approach in a novel application for the identification of antifungal compounds produced by lactic acid bacteria cultures. AB - Lactic Acid Bacteria (LAB) play an important role as natural food preservatives in many fermented food systems. To-date, characterisation of their diverse range of metabolites has been limited. Improved quantitation of low, medium and high concentration antifungal compounds is required, ensuring that both known and unknowns compounds are identified. This manuscript reports the first application of QuEChERS (quick, easy, cheap, effective, rugged and safe) for the extraction of natural antifungal metabolites in LAB cultures. The method provides improved individual recoveries (>78%) for 15 known antifungal compounds, an improvement of 26% compared to previously reported techniques (>52%). A protocol was developed that allowed LAB cultures to be easily assessed on a fully validated high performance liquid chromatography with ultra violet/diode array detection (HPLC UV/DAD) method. Previously reported methods involving direct injection of filtered extracts and SPE clean-up, suffered from a rise in chromatographic baseline due to interfering matrix components, limiting accurate quantitation. This QuEChERS method removed these interfering matrix components to deliver clean chromatograms with greater recoveries (78.2-127.4%) and lower RSD values (2.5 10.8%) of all 15 antifungal compounds. The validated method was applied to LAB strains showing particularly strong antifungal activity and provided an increase in the number of compounds detected (both known and unknown) compared to previous techniques for the same strains, due to the improved recoveries now possible by this method. Confirmation of the compounds identified was performed by analysis on a liquid chromatography linear ion trap quadrupole Orbitrap hybrid Fourier transform mass spectrometer (LC-FTMS). This first application of QuEChERS to LAB cultures has significantly improved the analytical capabilities of antifungal compound profiling especially where the synergy of numerous compounds is suspected as producing the observed activity. LAB cultures can now be easily integrated into various food matrices, as natural food preservatives, now that a complete analyte profile is achievable. PMID- 25127609 TI - Simultaneous voltammetric determination of paracetamol and ascorbic acid using a boron-doped diamond electrode modified with Nafion and lead films. AB - The paper describes the fabrication and application of a novel sensor (a boron doped diamond electrode modified with Nafion and lead films) for the simultaneous determination of paracetamol and ascorbic acid by differential pulse voltammetry. The main advantage of the lead film and polymer covered boron-doped diamond electrode is that the sensitivity of the stripping responses is increased and the separation of paracetamol and ascorbic acid signals is improved due to the modification of the boron-doped diamond surface by the lead layer. Additionally, the repeatability of paracetamol and ascorbic acid signals is improved by the application of the Nafion film coating. In the presence of oxygen, linear calibration curves were obtained in a wide concentration range from 5*10(-7) to 2*10(-4) mol L(-1) for paracetamol and from 1*10(-6) to 5*10(-4) mol L(-1) for ascorbic acid. The analytical utility of the differential pulse voltammetric method elaborated was tested in the assay of paracetamol and ascorbic acid in commercially available pharmaceutical formulations and the method was validated by high performance liquid chromatography coupled with diode array detector. PMID- 25127610 TI - Optimization of the in-needle extraction device for the direct flow of the liquid sample through the sorbent layer. AB - In-needle extraction was applied for preparation of aqueous samples. This technique was used for direct isolation of analytes from liquid samples which was achieved by forcing the flow of the sample through the sorbent layer: silica or polymer (styrene/divinylbenzene). Specially designed needle was packed with three different sorbents on which the analytes (phenol, p-benzoquinone, 4-chlorophenol, thymol and caffeine) were retained. Acceptable sampling conditions for direct analysis of liquid sample were selected. Experimental data collected from the series of liquid samples analysis made with use of in-needle device showed that the effectiveness of the system depends on various parameters such as breakthrough volume and the sorption capacity, effect of sampling flow rate, solvent effect on elution step, required volume of solvent for elution step. The optimal sampling flow rate was in range of 0.5-2 mL/min, the minimum volume of solvent was at 400 uL level. PMID- 25127608 TI - A simple, fast and cheap non-SPE screening method for antibacterial residue analysis in milk and liver using liquid chromatography-tandem mass spectrometry. AB - In routine laboratory work, screening methods for multiclass analysis can process a large number of samples in a short time. The main challenge is to develop a methodology to detect as many different classes of residues as possible, combined with speed and low cost. An efficient technique for the analysis of multiclass antibacterial residues (fluoroquinolones, tetracyclines, sulfonamides and trimethoprim) was developed based on simple, environment-friendly extraction for bovine milk, cattle and poultry liver. Acidified ethanol was used as an extracting solvent for milk samples. Liver samples were treated using EDTA-washed sand for cell disruption, methanol:water and acidified acetonitrile as extracting solvent. A total of 24 antibacterial residues were detected and confirmed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), at levels between 10, 25 and 50% of the maximum residue limit (MRL). For liver samples a metabolite (sulfaquinoxaline-OH) was also monitored. A validation procedure was conducted for screening purposes in accordance with European Union requirements (2002/657/EC). The detection capability (CCbeta) false compliant rate was less than 5% at the lowest level for each residue. Specificity and ruggedness were also discussed. Incurred and routine samples were analyzed and the method was successfully applied. The results proved that this method can be an important tool in routine analysis, since it is very fast and reliable. PMID- 25127611 TI - Dual hairpin-like molecular beacon based on coralyne-adenosine interaction for sensing melamine in dairy products. AB - This study presents a novel dual hairpin-like molecular beacon (MB) for the selective and sensitive detection of melamine (MA) based on the conjugation of MA and thymine. In this protocol, the coordination between coralyne and adenosine (A) leaded a dual hairpin-like MB and the fluorophore-quencher pair is close proximity resulting in the fluorescence quenching. With the addition of MA, it conjugated with thymine in the loop part of dual hairpin-like MB by triple H bonds, triggering the dissociation of the dual hairpin-like MB. The resulting spatial separation of the fluorophore from quencher induced the enhancement in fluorescence emission. Under the optimized conditions, the sensor exhibited a wide linear range of 8*10(-9)-1.6*10(-5) M (R(2)=0.9969) towards MA, with a low detection limit of 5 nM, approximately 4000 times lower than the Drug Administration and the US Food estimated MA safety limit. The real milk samples were also investigated with a satisfying result. PMID- 25127612 TI - Microwave assisted extraction-solid phase extraction for high-efficient and rapid analysis of monosaccharides in plants. AB - Monosaccharides are the fundamental composition units of saccharides which are a common source of energy for metabolism. An effective and simple method consisting of microwave assisted extraction (MAE), solid phase extraction (SPE) and high performance liquid chromatography-refractive index detector (HPLC-RID) was developed for rapid detection of monosaccharides in plants. The MAE was applied to break down the structure of the plant cells and release the monosaccharides, while the SPE procedure was adopted to purify the extract before analysis. Finally, the HPLC-RID was employed to separate and analyze the monosaccharides with amino column. As a result, the extraction time was reduced to 17 min, which was nearly 85 times faster than soxhlet extraction. The recoveries of arabinose, xylose, fructose and glucose were 85.01%, 87.79%, 103.17%, and 101.24%, with excellent relative standard deviations (RSDs) of 1.94%, 1.13%, 0.60% and 1.67%, respectively. The proposed method was demonstrated to be efficient and time saving, and had been applied to analyze monosaccharides in tobacco and tea successfully. PMID- 25127613 TI - Facile fabrication of an ultrasensitive sandwich-type electrochemical immunosensor for the quantitative detection of alpha fetoprotein using multifunctional mesoporous silica as platform and label for signal amplification. AB - A novel and ultrasensitive sandwich-type electrochemical immunosensor was designed for the quantitative detection of alpha fetoprotein (AFP) using multifunctional mesoporous silica (MCM-41) as platform and label for signal amplification. MCM-41 has high specific surface area, high pore volume, large density of surface silanol groups (SiOH) and good biocompatibility. MCM-41 functionalized with 3-aminopropyltriethoxysilane (APTES), gold nanoparticles (Au NPs) and toluidine blue (TB) could enhance electrochemical signals. Moreover, primary antibodies (Ab1) and secondary antibodies (Ab2) could be effectively immobilized onto the multifunctional MCM-41 by the interaction between Au NPs and amino groups (-NH2) on antibodies. Using multifunctional MCM-41 as a platform and label could greatly simplify the fabrication process and result in a high sensitivity of the designed immunosensor. Under optimal conditions, the designed immunosensor exhibited a wide liner range from 10(-4) ng/mL to 10(3) ng/mL with a low detection limit of 0.05 pg/mL for AFP. The designed immunosensor showed acceptable selectivity, reproducibility and stability, which could provide potential applications in clinical monitoring of AFP. PMID- 25127614 TI - Determination of mercury in river water by diffusive gradients in thin films using P81 membrane as binding layer. AB - In this work, a device based on diffusive gradients in thin films (DGT) was evaluated for the determination of Hg(II) in river water. The DGT device was assembled with a cellulose phosphate ion exchange membrane (P81 Whatman) as a binding phase and agarose gel 1.5% (m/v) as a diffusive layer. Laboratory deployments showed that the binding of Hg(2+) ([Hg(DGT)]/[Hg(solution)]) by P81 membrane was more effective (97%) than the Chelex 100 resin (80%).The effect of ionic strength, pH and potential interfering ions on Hg binding with DGT's was investigated. The results showed no significant effect on the binding of Hg(II) at pH range from 3.5 to 8.5 and at an ionic strength range from 0.0005 to 0.1 mol L(-1). Uptakes of 50 ug L(-1) Hg(II) by P81 membrane were not affected by Fe, Mn, Zn, Cu, Ca and Mg at the concentration range of 200-1800 ug L(-1). Finally, the DGT device using the P81 as the binding layer was applied for in situ measurements of Hg in river water. For in situ measurements, the labile Hg concentration (from <2 to 13 ng L(-1)) was lower than 10% of the dissolved fraction (from 155 to 446 ng L(-1)). PMID- 25127616 TI - Sulfonated polystyrene magnetic nanobeads coupled with immunochromatographic strip for clenbuterol determination in pork muscle. AB - A magnetic solid-phase extraction method (MSPE) was developed to pre-concentrate and cleanup clenbuterol (CLE) from pork muscle. Novel sulfonated polystyrene magnetic nanobeads (spMNBs) were synthesized via a one-pot emulsion copolymerization method by using divinylbenzene, styrene, and sodium styrene sulfonate in the presence of oleic acid-modified and 10-undecylenic acid-modified magnetic ferrofluid. The resulting spMNBs exhibited high adsorption efficiency for CLE and for 10 other common beta-adrenergic agonists, namely, brombuterol, ractopamine, tulobuterol, bambuterol, cimbuterol, mabuterol, clorprenaline, penbutolol, salbutamol, and cimaterol. The adsorption behavior of the spMNBs for CLE was described by the Langmuir equation with a maximum adsorption capacity of 0.41 mg/g. Under the optimized parameters, the extraction of CLE from 0.5 g of pork muscle required 25mg of the spMNBs at a shortened adsorption time (0.5 min). The proposed MSPE was coupled with colloidal gold nanoparticle-based immunochromatographic assay (MSPE-AuNPIA) for the quantitative detection of CLE residue in pork muscle. The limit of detection and limit of quantification for the pork muscle were 0.10 and 0.24 ng/g, respectively. The intra-day and inter day assay recoveries at three CLE spiked concentrations ranged from 92.5% to 98.1%, with relative standard deviations ranging from 3.2% to 13.0%. The results of MSPE-AuNPIA were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CLE values obtained with MSPE-AuNPIA agreed with those obtained with LC-MS/MS. PMID- 25127617 TI - Investigation on performance of zirconia and magnesia-zirconia stationary phases in hydrophilic interaction chromatography. AB - In the current study, zirconia (ZrO2) and its composite, magnesia-zirconia (MgO ZrO2), were prepared as the hydrophilic interaction chromatographic (HILIC) stationary phases (SPs). Different experimental variables including water content, pH and buffer concentration in the mobile phase (MP) as well as column temperature were systematically studied to permit an in-depth understanding of the chromatographic properties of the mentioned SPs and to explore the retention mechanism further on. The results were compared with a native SiO2 column. Adsorption was demonstrated as the main retention mechanism on the two ZrO2-based SPs. The transferring of the analytes from the MP to the ZrO2-based SPs was endothermic and high column temperature would facilitate the retention. In addition, the MgO-ZrO2 SP exhibited superior resolution, column efficiency as well as stronger retention in comparison to the bare ZrO2 SP, which demonstrated that the introduction of MgO could improve the structure and properties of the material. In conclusion, MgO-ZrO2 was a promising material for HILIC applications. PMID- 25127615 TI - Detection of potato brown rot and ring rot by electronic nose: from laboratory to real scale. AB - A commercial electronic nose (e-nose) equipped with a metal oxide sensor array was trained to recognize volatile compounds emitted by potatoes experimentally infected with Ralstonia solanacearum or Clavibacter michiganensis subsp. sepedonicus, which are bacterial agents of potato brown and ring rot, respectively. Two sampling procedures for volatile compounds were tested on pooled tubers sealed in 0.5-1 L jars at room temperature (laboratory conditions): an enrichment unit containing different adsorbent materials (namely, Tenax((r)) TA, Carbotrap, Tenax((r)) GR, and Carboxen 569) directly coupled with the e-nose (active sampling) and a Radiello(TM) cartridge (passive sampling) containing a generic Carbograph fiber. Tenax((r)) TA resulted the most suitable adsorbent material for active sampling. Linear discriminant analysis (LDA) correctly classified 57.4 and 81.3% total samples as healthy or diseased, when using active and passive sampling, respectively. These results suggested the use of passive sampling to discriminate healthy from diseased tubers under intermediate and real scale conditions. 80 and 90% total samples were correctly classified by LDA under intermediate (100 tubers stored at 4 degrees C in net bag passively sampled) and real scale conditions (tubers stored at 4 degrees C in 1.25 t bags passively sampled). Principal component analysis (PCA) of sensorial analysis data under laboratory conditions highlighted a strict relationship between the disease severity and the responses of the e-nose sensors, whose sensitivity threshold was linked to the presence of at least one tuber per sample showing medium disease symptoms. At intermediate and real scale conditions, data distribution agreed with disease incidence (percentage of diseased tubers), owing to the low storage temperature and volatile compounds unconfinement conditions adopted. PMID- 25127618 TI - Analytical methods for the determination of personal care products in human samples: an overview. AB - Personal care products (PCPs) are organic chemicals widely used in everyday human life. Nowadays, preservatives, UV-filters, antimicrobials and musk fragrances are widely used PCPs. Different studies have shown that some of these compounds can cause adverse health effects, such as genotoxicity, which could even lead to mutagenic or carcinogenic effects, or estrogenicity because of their endocrine disruption activity. Due to the absence of official monitoring protocols, there is an increasing demand of analytical methods that allow the determination of those compounds in human samples in order to obtain more information regarding their behavior and fate in the human body. The complexity of the biological matrices and the low concentration levels of these compounds make necessary the use of advanced sample treatment procedures that afford both, sample clean-up, to remove potentially interfering matrix components, as well as the concentration of analytes. In the present work, a review of the more recent analytical methods published in the scientific literature for the determination of PCPs in human fluids and tissue samples, is presented. The work focused on sample preparation and the analytical techniques employed. PMID- 25127619 TI - First use of portable system coupling X-ray diffraction and X-ray fluorescence for in-situ analysis of prehistoric rock art. AB - Study of prehistoric art is playing a major role in the knowledge of human evolution. Many scientific methods are involved in this investigation including chemical analysis of pigments present on artefacts or applied to cave walls. In the past decades, the characterization of coloured materials was carried on by taking small samples. This procedure had two main disadvantages: slight but existing damage of the paintings and limitation of the number of samples. Thanks to the advanced development of portable systems, in-situ analysis of pigment in cave can be now undertaken without fear for this fragile Cultural Heritage. For the first time, a portable system combining XRD and XRF was used in an underground and archaeological environment for prehistoric rock art studies. In situ non-destructive analysis of black prehistoric drawings and determination of their composition and crystalline structure were successfully carried out. Original results on pigments used 13,000 years ago in the cave of Rouffignac (France) were obtained showing the use of two main manganese oxides: pyrolusite and romanechite. The capabilities of the portable XRD-XRF system have been demonstrated for the characterization of pigments as well as for the analysis of rock in a cave environment. This first in-situ experiment combining X-ray diffraction and X-ray fluorescence open up new horizons and can fundamentally change our approach of rock art studies. PMID- 25127620 TI - A novel restricted access material combined to molecularly imprinted polymers for selective solid-phase extraction and high performance liquid chromatography determination of 2-methoxyestradiol in plasma samples. AB - A feasibility study was performed in order to ensure the possibilities in using a restricted access material combined to molecularly imprinted polymers (RAM-MIP) as sorbent material in solid phase extraction (SPE) for clean-up of 2 methoxyestradiol (2-ME) from plasma samples. The MIP with hydrophilic external layer was designed by precipitation polymerization. The polymer was characterized by thermogravimetric analysis (TGA) and scanning electron microscope (SEM). The use of analogs of 2-ME as templates, in combination with a chromatographic separation of the analytes in the sample, overcame the problem of the template bleeding. To demonstrate the property of the RAM-MIP obtained, a comparison of commercially available C18 SPE was performed. The results showed that the RAM MISPE recoveries were significantly higher than that of C18 SPE for 2-ME in trace concentration. During the extraction process, 2-ME was sufficiently cleaned for further chromatographic analysis with no interferences from template leakage and matrix. Good linearity was obtained from 0.06 to 20 MUg mL(-1) with the correlation coefficient r>0.9991. The coefficient of variation of the inter-assay precision was less than 11.9%. The recoveries of 2-ME in rat plasma at three spiked levels were in the range of 99.10-101.00%. Based on the analytical validation results, the proposed method (RAM-MIP off-line SPE/HPLC) can be a useful tool to determine 2-ME in rat plasma samples. PMID- 25127621 TI - Application of multivariate chemometric techniques for simultaneous determination of five parameters of cottonseed oil by single bounce attenuated total reflectance Fourier transform infrared spectroscopy. AB - Single bounce attenuated total reflectance (SB-ATR) Fourier transform infrared (FTIR) spectroscopy in conjunction with chemometrics was used for accurate determination of free fatty acid (FFA), peroxide value (PV), iodine value (IV), conjugated diene (CD) and conjugated triene (CT) of cottonseed oil (CSO) during potato chips frying. Partial least square (PLS), stepwise multiple linear regression (SMLR), principal component regression (PCR) and simple Beer's law (SBL) were applied to develop the calibrations for simultaneous evaluation of five stated parameters of cottonseed oil (CSO) during frying of French frozen potato chips at 170 degrees C. Good regression coefficients (R(2)) were achieved for FFA, PV, IV, CD and CT with value of >0.992 by PLS, SMLR, PCR, and SBL. Root mean square error of prediction (RMSEP) was found to be less than 1.95% for all determinations. Result of the study indicated that SB-ATR FTIR in combination with multivariate chemometrics could be used for accurate and simultaneous determination of different parameters during the frying process without using any toxic organic solvent. PMID- 25127622 TI - Measurement of U and Pu isotope ratios in hair and nail samples using extraction chromatography and multi-collector inductively coupled plasma mass spectrometry. AB - A bioassay capable of monitoring occupational or environmental exposure to special nuclear materials would be a useful tool for nuclear nonproliferation programs. Hair and nail are potential biomonitors of exposure to U and Pu. A method is described to measure isotope ratios of ultra-trace concentrations of U and Pu in hair and nail samples. The method uses multiple extraction chromatography resins to separate U and Pu fractions from the sample matrix. The U recovery was quantitative while the Pu recovery ranged from 81% to 109%, with a U decontamination factor of 5*10(4). Following the separation (234)U/(238)U, (235)U/(238)U and (240)Pu/(239)Pu were measured in human hair and hair and nail samples using multi-collector inductively coupled plasma mass spectrometry (MC ICPMS). The human hair and nail samples had elevated ratios of (234)U/(238)U which could reflect exposure to naturally fractionated U. PMID- 25127623 TI - Comparison of different types of diffusive gradient in thin film samplers for measurement of dissolved methylmercury in freshwaters. AB - Determination of bioavailable concentrations of methylmercury (MeHg(+)) in freshwater is key to further understanding its potential risk and toxicity. In this work, two in-house-manufactured mercury-specific diffusive gradients in thin films (DGT) were used in laboratory to assess the lability of MeHg(+), and to develop a relationship between chemical lability and bioavailability. After diffusing through the diffusive gel, the MeHg(+) accumulated in a thiol functionalised resin gel was extracted using acidic thiourea that was analysed using aqueous-phase propylation followed by headspace solid-phase microextraction (HS-SPME) and gas chromatography (GC) coupled to pyrolysis-atomic fluorescence spectrometry (Py-AFS) detection. The diffusion coefficient (D) at 25 degrees C in agarose (A-DGT) in the absence and presence of dissolved organic matter (DOM) was obtained. Moreover, these values were experimentally compared against polyacrylamide (P-DGT), which is the most frequently used DGT for mercury to date. Statistically significant differences were observed between D values for A DGT in the absence (3.15*10(-6) cm(2) s(-1)) and presence of DOM (2.68*10(-6) cm(2) s(-1)) and also for P-DGT (2.49*10(-6) and 1.69*10(-6) cm(2) s(-1)). Interestingly, our results show that diffusion of MeHg(+) was higher on agarose diffusive gel with and without DOM in comparison with those observed in polyacrylamide. Even with higher diffusion coefficients of MeHg(+) in the agarose diffusion layer, however, DGT based on polyacrylamide seems to be a better choice for eutrophic waters, when monitoring very low concentrations of MeHg(+), considering its slightly higher uptake capacity. PMID- 25127624 TI - Low cost microfluidic cell culture array using normally closed valves for cytotoxicity assay. AB - A reusable low cost microfluidic cell culture array device (MCCAD) integrated with a six output concentration gradient generator (cGG) and 4*6 arrays of microchamber elements, addressed by a series of row and columnar pneumatically actuated normally closed (NC) microvalves was fabricated for cell-based screening of chemotherapeutic compounds. The poly(dimethylsiloxane) (PDMS) device consists of three layers: fluidic, control and membrane which are held by surface contact and made leak-proof by clamping pressure. The NC valves are actuated by a thick PDMS membrane that was created by a novel method based on the self-assembly of PDMS pre-polymer molecules over a denser calcium chloride solution. The membrane actuated the valves reliably and particulates such as alumina particles (3 um) and MCF-7 cells (20-24 um) (2*10(5) cells/mL) were flowed through the valves without causing blockage or leakage and consequently avoiding contamination of the different cell culture elements. The MCCAD was cast and assembled in a standard laboratory without specialist equipment and demonstrated for performing quantitative cell-based cytotoxicity assays of pyocyanine on human breast cancer (MCF-7) cells and assessed for toxic effect on human hepatocyte carcinoma (HepG2) cells as an indicator for liver injury. Then, the MCCAD was demonstrated for sequential drug combinatorial screening involving gradient generation of paclitaxel doses followed by treatment with aspirin doses on the viability of MCF 7 cells. The interaction between paclitaxel and aspirin was evaluated by using the Bliss independence predictive model and results showed reasonable agreement with the model. A robust, portable, easily fabricated and low cost device is therefore shown to conveniently carry out culturing of multiple cell lines for high throughput screening of anti-cancer compounds using minimal reagents. PMID- 25127625 TI - Application of neodymium isotope ratio measurements for the origin assessment of uranium ore concentrates. AB - A novel procedure has been developed for the measurement of (143)Nd/(144)Nd isotope ratio in various uranium-bearing materials, such as uranium ores and ore concentrates (UOC) in order to evaluate the usefulness and applicability of variations of (143)Nd/(144)Nd isotope ratio for provenance assessment in nuclear forensics. Neodymium was separated and pre-concentrated by extraction chromatography and then the isotope ratios were measured by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). The method was validated by the measurement of standard reference materials (La Jolla, JB-2 and BCR-2) and the applicability of the procedure was demonstrated by the analysis of uranium samples of world-wide origin. The investigated samples show distinct (143)Nd/(144)Nd ratio depending on the ore type, deposit age and Sm/Nd ratio. Together with other characteristics of the material in question, the Nd isotope ratio is a promising signature for nuclear forensics and suggests being indicative of the source material, the uranium ore. PMID- 25127626 TI - Assessment of gas chromatography time-of-flight accurate mass spectrometry for identification of volatile and semi-volatile compounds in honey. AB - The performance of gas chromatography (GC) combined with a hybrid quadrupole time of-flight (QTOF) mass spectrometry (MS) system for the determination of volatile and semi-volatile compounds in honey samples is evaluated. After headspace (HS) solid-phase microextraction (SPME) of samples, the accurate mass capabilities of the above system were evaluated for compounds identification. Accurate scan electron impact (EI) MS spectra allowed discriminating compounds displaying the same nominal masses, but having different empirical formulae. Moreover, the use of a mass window with a width of 0.005 Da provided highly specific chromatograms for selected ions, avoiding the contribution of interferences to their peak areas. Additional information derived from positive chemical ionization (PCI) MS spectra and ion product scan MS/MS spectra permitted confirming the identity of novel compounds. The above possibilities are illustrated with examples of honey aroma compounds, belonging to different chemical classes and containing different elements in their molecules. Examples of compounds whose structures could not be described are also provided. Overall, 84 compounds, from a total of 89 species, could be identified in 19 honey samples from 3 different geographic areas in the world. The suitability of responses measured for selected ions, corresponding to above species, for authentication purposes is assessed through principal components analysis. PMID- 25127627 TI - Fluorescence method using on-line sodium cholate coacervate surfactant mediated extraction for the flow injections analysis of Rhodamine B. AB - An on-line surfactant mediated extraction method in a flow injection analysis format with fluorescence detection was developed for the determination of Rhodamine B (RhB) in food condiments. The sample was extracted using the phase separation behavior exhibited by the bile salt surfactant, sodium cholate (NaC), upon addition of sodium dodecylsulfate (SDS) in the presence of acid at room temperature. The RhB in the sample was incorporated into the NaC/SDS coacervate phase which was then collected on a glass-wool packed mini column from which it was subsequently eluted using a 1.00 mol L(-1) HCl solution. The inherent fluorescence (lambdaex=555 nm; lambdaem=575 nm) of RhB was employed for detection. Good linearity (r(2)=0.9933) was obtained over the concentration range 0.4-4794-479.0 ug L(-1) RhB. The detection (LOD) and quantification (LOQ) limits were 0.12 and 0.40 ug L(-1), respectively. The method was successfully applied for analysis of RhB in food condiments and spiked samples. The average recoveries ranged from 95.3% to 118.9% at spiked concentration levels of 1.19 and 2.39 ug L( 1). Under optimized conditions, a throughput of 50 samples per hour was achieved. The proposed method may be a valuable tool not only for quality control of food condiments and similar food confectioneries but for the analysis of a variety of other RhB-containing samples as well. PMID- 25127628 TI - Gr-Pt hybrid NP modified GCPE as label and indicator free electrochemical genosensor platform. AB - Glassy carbon paste electrode (GCPE) was modified with graphene platinum hybrid nanoparticle (Gr-Pt hybrid NP) and used as a transducer for label and indicator free electrochemical genosensor. 22 mer oligonucleotides representing Escherichia coli bacteria were used as a model case. As far as it is known, this study is the first study where Gr-Pt hybrid NP was incorporated into GCPE and used for genosensor transducer. The extent of hybridization was determined by using differential pulse voltammetric signals of guanin oxidation. After the optimization of experimental parameters, analytical characteristics were investigated. The linear range was found between 1.5*10(-7) and 2.25*10(-6) M with the equation of y=1.6566x-2.6161 and R(2) of 0.9959. RSD and LOD were calculated as 4.2% (n=6) and 1.12*10(-9) M respectively. PMID- 25127629 TI - High-performance liquid chromatographic and mass spectrometric analysis of fluorescent carbon nanodots. AB - Amino/hydroxyl-functionalized fluorescent carbon nanodots (C-NanoD) are conveniently synthesized based on hydrothermal carbonization of chitosan at 180 degrees C. Dialysis membranes with small cut-off masses (500-1000 Da) were found useful for removing the side-products and low molecular mass species to purify the C-NanoD product. Herein, reversed-phase high-performance liquid chromatography (RP-HPLC) has been successfully applied to fractionate the C-NanoD product. The elution order of the C-NanoD species present in the sample follows approximately their core sizes from small to large. The separated C-NanoD fractions are collected and characterized by UV absorption spectroscopy, photoluminescence (PL) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and transmission electron microscopy (TEM). All the C-NanoD fractions display a distinctive absorption band at 300 nm, attributing to the n->pi* transition of C=O bond. The PL spectra of the fractions display emission peaks at 400-415 nm which are slightly red-shifted with their increase in relative molecular masses. The C-NanoD fractions are fully anatomized by MALDI-TOF MS, displaying their fragmentation mass ion features. The core sizes of some selected C-NanoD are determined as 1.6, 1.8, 2.5, and 3.1 nm by TEM which are in consistent with their HPLC elution order. The findings highlight the virtues of RP-HPLC to fractionate and reveal the unique characteristics of individual C-NanoD species present in an as-synthesized C NanoD product which may have potential applications in the fields of bioanalysis, bioimaging, catalysis, chemosensing, energy storage, and optoelectronics device. PMID- 25127630 TI - A fluorescence glucose sensor based on pH induced conformational switch of i motif DNA. AB - A facile fluorescence biosensor for the detection of glucose is proposed based on the pH-induced conformational switch of i-motif DNA in this paper. Glucose can be oxidized by oxygen (O2) in the presence of glucose oxidase (GOD), and the generated gluconic acid can decrease the pH value of the solution and then induce the fluorophore- and quencher-labeled cytosine-rich single-stranded DNA to fold into a close-packed i-motif structure. As a result, the fluorescence quenching occurs because of the resonance energy transfer between fluorophore and quencher. Based on this working principle, the concentration of glucose can be detected by the decrease of fluorescence density. Under the optimal experimental conditions, the assay shows a linear response range of 5-100 uM for the glucose concentration with a detection limit of 4 uM. This glucose biosensor was applied to determine glucose in real samples successfully, suggesting its potential in the practical applicability. PMID- 25127631 TI - Impedimetric detection of alcohol vapours using nanostructured zinc ferrite. AB - A comparative study on the sensing characteristics of nanostructured zinc ferrite to three primary alcohols viz. methanol, ethanol and propanol has been carried out. The zinc ferrite has been prepared by a combustion method and characterized by XRD, FTIR, AFM and SEM. Impedance studies in the alcohol concentration range varying from 100 to 1000 ppm show definite variations in response to both the nature of the alcohol and its concentration. The nanostructured zinc ferrite shows the highest sensor response to methanol and least to propanol. Equivalent circuit modelling and calibration have been made for all the three alcohol sensors. The material shows a better selectivity to the alcohols compared to formaldehyde, ammonia and acetone vapours. PMID- 25127632 TI - A new analytical method to determine non-steroidal anti-inflammatory drugs in surface water using in situ derivatization combined with ultrasound-assisted emulsification microextraction followed by gas chromatography-mass spectrometry. AB - Because of the high stability and potential toxic effects of non-steroidal anti inflammatory drugs (NSAIDs), it is important to closely monitor their concentrations in the environment using a sensitive analytical method. In this study, a simple, rapid, efficient, and sensitive analytical method based on gas chromatography-mass spectrometry (GC-MS) was developed to determine the levels of seven common NSAIDs in various types of surface water. To simplify sample preparation, in situ derivatization using methyl chloroformate was combined with ultrasound-assisted emulsification microextraction. For selection and optimization of significant variables, experiments were statistically designed using Plackett-Burman design and central composite design. The resulting optimal conditions for derivatization and extraction were 100 MUL of chloroform (extraction solvent), 10.0 mL of sample, and 240 MUL of pyridine (catalyst as a base in derivatization). The optimized sample preparation coupled with optimized GC-MS analysis in selected ion monitoring mode provided good linearity from 0.010 to 5.0 ng mL(-1), and a limit of detection between 0.0050 and 0.010 ng mL(-1), good intra-day and inter-day precision (0.30-6.3% and 5.1-9.5%, respectively), and good accuracy (relative recovery; 91-117% at 0.20 ng mL(-1) and 77-105% at 2.5 ng mL(-1)). Compared with previously reported methods, the current method requires a small volume of sample and simple sample preparation steps for sensitive determination of NSAID levels using a conventional GC-MS system. The method was successfully applied to determine the levels of seven common NSAIDs in various types of surface water. PMID- 25127633 TI - The use of a polymer inclusion membrane as a sorbent for online preconcentration in the flow injection determination of thiocyanate impurity in ammonium sulfate fertilizer. AB - A polymer inclusion membrane (PIM) is used for the first time as a sorbent in the construction of a preconcentration column to enhance the sensitivity in flow injection analysis (FIA). The PIM-coated column is readily prepared by coating the PIM containing poly(vinyl chloride), Aliquat 336, and 1-tetradecanol onto glass beads packed in a glass tube. The determination of trace amounts of thiocyanate in ammonium sulfate fertilizer demonstrates the potential of the proposed PIM-coated column in FIA. Thiocyanate standards or samples of relatively large volume (e.g. up to 2000 uL) are injected into a nitrate carrier stream. The sample zone passes through the proposed preconcentration column where thiocyanate is concentrated in a smaller volume of a carrier solution thus resulting in up to 7.4 fold increase in sensitivity. Thiocyanate is detected spectrophotometrically after its reaction with Fe(III) downstream of the preconcentration column. The limits of detection of thiocyanate in the absence and presence of 20 g L(-1) ammonium sulfate (S/N=2) are 0.014 and 0.024 mg L(-1), respectively. Thiocyanate was successfully determined in several samples of ammonium sulfate fertilizer. PMID- 25127634 TI - Facile preparation of octadecyl monoliths with incorporated carbon nanotubes and neutral monoliths with coated carbon nanotubes stationary phases for HPLC of small and large molecules by hydrophobic and pi-pi interactions. AB - Two approaches for incorporating carbon nanotubes into monolithic columns for HPLC are described in this report. They pertain to the investigation of carbon nanotubes either (i) as entities to modulate solute retention on monolithic columns bearing well defined retentive ligands or (ii) as entities that constitute the stationary phase responsible for solute retention and separation. Approach (i) involved the incorporation of carbon nanotubes into octadecyl monolithic columns while approach (ii) concerns the preparation and evaluation of an ideal monolithic support and coating it with carbon nanotubes to yield a real "carbon nanotube stationary phase" for the HPLC separation of a wide range of solutes. First, an octadecyl monolithic column based on the in situ polymerization of octadecyl acrylate and trimethylolpropane trimethacrylate was optimized for use in HPLC separations of small and large solutes (e.g., proteins). To further modulate the retention and separation of proteins, small amounts of carbon nanotubes were incorporated into the octadecyl monolith column. In approach (ii), an inert, relatively polar monolith based on the in situ polymerization of glyceryl monomethacrylate (GMM) and ethylene glycol dimethacrylate (EDMA) proved to be the most suitable support for the preparation of "carbon nanotube stationary phase". This carbon nanotube "coated" monolith proved useful in the HPLC separation of a wide range of small solutes including enantiomers. In approach (ii), a more homogeneous incorporation of carbon nanotubes into the diol monolithic columns (i.e., GMM/EDMA) was achieved when hydroxyl functionalized carbon nanotubes were incorporated into the GMM/EDMA monolithic support. In addition, high power sonication for a short time enhanced further the homogeneity of the monolith incorporated with nanotubes. In all cases, nonpolar and pi interactions were responsible for solute retention on the monolith incorporated carbon nanotubes. PMID- 25127635 TI - Low gas flow inductively coupled plasma optical emission spectrometry for the analysis of food samples after microwave digestion. AB - In this work, the recently introduced low flow inductively coupled plasma optical emission spectrometry (ICP-OES) with a total argon consumption below 0.7 L/min is applied for the first time to the field of food analysis. One goal is the investigation of the performance of this low flow plasma compared to a conventional ICP-OES system when non-aqueous samples with a certain matrix are introduced into the system. For this purpose, arsenic is determined in three different kinds of fish samples. In addition several nutrients (K, Na, Mg, Ca) and trace metals (Co, Cu, Mn, Cd, Pb, Zn, Fe, and Ni) are determined in honey samples (acacia) after microwave digestion. The precision of the measurements is characterized by relative standard deviations (RSD) and compared to the corresponding precision values achieved using the conventional Fassel-type torch of the ICP. To prove the accuracy of the low flow ICP-OES method, the obtained data from honey samples are validated by a conventional ICP-OES. For the measurements concerning arsenic in fish, the low flow ICP-OES values are validated by conventional Fassel-type ICP-OES. Furthermore, a certified reference material was investigated with the low gas flow setup. Limits of detection (LOD), according to the 3sigma criterion, were determined to be in the low microgram per liter range for all analytes. Recovery rates in the range of 96-106% were observed for the determined trace metal elements. It was proven that the low gas flow ICP-OES leads to results that are comparable with those obtained with the Fassel-type torch for the analysis of food samples. PMID- 25127636 TI - New method for the determination of carbamate and pyrethroid insecticides in water samples using on-line SPE fused core column chromatography. AB - A new HPLC column-switching method using large volume sample injection and fused core columns for on-line solid phase extraction have been developed for the determination of the following carbamates and pyrethroids: aldicarb, carbaryl, pirimicarb, carbofuran, kadethrin, flumethrin, fenpropathrin, fenoxycarb, tau fluvalinate and fenvalerate, in surface water samples. Sudan I was used as internal standard. The proposed method was performed using 100 ul sample injection followed by an on-line solid phase extraction procedure and finally the compounds were identified and quantified by liquid chromatography with ultraviolet detection. The separation was carried out on C-18 reversed phase column based on fused-core particle technology. The influence of the injected sample volume, the variables affecting to SPE process and the conditions for the separation on an analytical column, were studied and optimized. The limits of detection ranged from 5.5 to 8.9 ug L(-1), and limits of quantification from 18.4 to 29.7 ug L(-1), while inter- and intra-day variability was under 15%. This new analytical procedure was satisfactorily applied for the determination of these organic pollutants in surface water samples located in Czech Republic. Concentration levels were found for some of these pollutants up to 26.11 ug L(-1) in the river Elbe and up to 34.53 ug L(-1) in the closed lakes samples. PMID- 25127637 TI - Thermogravimetric study of vapor pressure of TATP synthesized without recrystallization. AB - This study aims at characterizing the vapor pressure signatures generated by triacetone triperoxide (TATP) that was synthesized without recrystallization by thermogravimmetric analysis (TGA) for exploitation by standoff detection technologies of explosive devices. The thermal behavior of the nonrecrystallized sample was compared with reported values. Any phase change, melting point and decomposition identification were studied by differential scanning calorimeter. Vapor pressures were estimated by the Langmuir method of evaporation from an open surface in a vacuum. Vapor pressures of TATP at different temperatures were calculated using the linear logarithmic relationship obtained from benzoic acid reference standard. Sublimation of TATP was found to follow apparent zero-order kinetics and sublimes at steady rates at 298 K and above. While the enthalpy of sublimation found, 71.7 kJ mol(-1), is in agreement with reported values the vapor pressures deviated significantly. The differences in the vapor pressures behavior are attributable to the synthesis pathway chosen in this study. PMID- 25127638 TI - Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2 ECD. AB - Human epidermal growth factor receptor 2 (HER2) is a breast cancer biomarker that plays a major role in promoting breast cancer cell proliferation and malignant growth. The extracellular domain (ECD) of HER2 can be shed into the blood stream and its concentration is measurable in the serum fraction of blood. In this work an electrochemical immunosensor for the analysis of HER2 ECD in human serum samples was developed. To achieve this goal a screen-printed carbon electrode, modified with gold nanoparticles, was used as transducer surface. A sandwich immunoassay, using two monoclonal antibodies, was employed and the detection of the antibody-antigen interaction was performed through the analysis of an enzymatic reaction product by linear sweep voltammetry. Using the optimized experimental conditions the calibration curve (ip vs. log[HER2 ECD]) was established between 15 and 100 ng/mL and a limit of detection (LOD) of 4.4 ng/mL was achieved. These results indicate that the developed immunosensor could be a promising tool in breast cancer diagnostics, patient follow-up and monitoring of metastatic breast cancer since it allows quantification in a useful concentration range and has an LOD below the established cut-off value (15 ng/mL). PMID- 25127639 TI - Polydimethylsiloxane/metal-organic frameworks coated fiber for solid-phase microextraction of polycyclic aromatic hydrocarbons in river and lake water samples. AB - In this study, polydimethylsiloxane/metal-organic frameworks (PDMS/MOFs), including PDMS/MIL-101 and PDMS/MOF-199, were immobilized onto a stainless steel wire through sol-gel technique as solid-phase microextraction (SPME) fiber coating. The prepared fibers were used for the extraction of some polycyclic aromatic hydrocarbons (PAHs) from water samples prior to gas chromatography-mass spectrometry (GC-MS) analysis. Under the optimized experiment conditions, the PDMS/MIL-101 coated fiber exhibited higher extraction efficiency towards PAHs than that of PDMS/MOF-199. Several parameters affecting the extraction of PAHs by SPME with PDMS/MIL-101 fiber, including the extraction temperature, extraction time, sample volume, salt addition and desorption conditions, were investigated. The limits of detection (LODs) were less than 4.0 ng L(-1) and the linearity was observed in the range from 0.01 to 2.0 ug L(-1) with the correlation coefficients (r) ranging from 0.9940 to 0.9986. The recoveries of the method for the PAHs from water samples at spiking levels of 0.05 and 0.2 ug L(-1) ranged from 78.2% to 110.3%. Single fiber repeatability and fiber-to-fiber reproducibility were less than 9.3% and 13.8%, respectively. PMID- 25127640 TI - Over a century of detection and quantification capabilities in analytical chemistry--historical overview and trends. AB - The detection limit (LD) and the quantification limit (LQ) are important parameters in the validation process. Estimation of these parameters is especially important when trace and ultra-trace quantities of analyte are to be detected. When the apparatus response from the analyte is below the detection limit, it does not necessarily mean that the analyte is not present in the sample. It may be a message that the analyte concentration could be below the detection capabilities of the instrument or analytical method. By using a more sensitive detector or a different analytical method it is possible to quantitatively determine the analyte in a given sample. The terms associated with detection capabilities have been present in the scientific literature for at least the past 100 years. Numerous terms, definitions and approaches to calculations have been presented during that time period. This paper is an attempt to collect and summarize the principal approaches to the definition and calculation of detection and quantification abilities published from the beginning of 20th century up until the present. Some of the most important methods are described in detail. Furthermore, the authors would like to popularize the knowledge of metrology in chemistry, particularly that part of it which concerns validation of the analytical procedure. PMID- 25127641 TI - A portable DNAzyme-based optical biosensor for highly sensitive and selective detection of lead (II) in water sample. AB - A portable, rapid and cost-effective DNAzyme based sensor for lead ions detection in water samples has been developed using an optical fiber sensor platform. The presence of Pb(2+) cleaves the DNAzymes and releases the fluorescent labeled fragments, which further hybridize with the complementary strands immobilized on the optic fiber sensor surface. Subsequent fluorescent signals of the hybridized fluorescent labeled fragment provides quantitative information on the concentrations of Pb(2+) with a dynamic range from 2-75 nM with a detection limit of 1.03 nM (0.21 ng mL(-1)). The proposed sensor also shows good selectivity against other mono and divalent metal ions and thus holds great potential for the construction of general DNAzyme-based sensing platform for the monitoring of other heavy metal ions. The sensor can be regenerated with a 1% SDS solution (pH 1.9) over 100 times without significant deterioration of the sensor performance. This portable sensor system can be potentially applied for on-site real-time inexpensive and easy-to-use monitoring of Pb(2+) in environmental samples such as wastewater effluents or water bodies. PMID- 25127642 TI - Development and characterisation of a new Sr selective resin for the rapid determination of 90Sr in environmental water samples. AB - A new resin selective for Sr has been developed and characterised for the direct binding of (90)Sr from environmental waters with minimal pre-treatment. The new selective resin comprises of a mixture of two extractants, 4,4'(5')-bis-t butylcyclohexano-18-crown-6 and di(2-ethyl-hexyl)phosphoric acid, sorbed onto Amberchrom CG-71. Sr uptake is shown to be high (the distribution weight coefficient Dw >100 mL g(-1)) across a range of environmentally realistic conditions (pH 2-8 and up to 11,500 mg L(-1) NaCl, 500 mg L(-1) Ca, 400 mg L(-1) K and 1300 mg L(-1) Mg). The Sr capacity of the resin is shown to be 7.7+/-0.4 mg g(-1), meaning that the resin has a sufficient capacity to quantitatively remove Sr from most environmental water samples. The reasonably fast uptake kinetics of the resin (95+/-4% of strontium bound within 30 min) results in a resin that is applicable to both batch- and column-type separation procedures. A range of potentially co-extracted radio-elements have been identified and an elution scheme has been developed to separate interferences, including (90)Y, from (90)Sr. The clean elution of (90)Sr permits immediate measurement by radiometric means, with no need for complicated spectral processing or waiting for secular equilibrium between (90)Sr and (90)Y. The characterised resin is applicable for use in rapid determination procedures, enabling the swift analysis of water samples required by monitoring schemes at contaminated nuclear sites and in the aftermath of nuclear accidents. PMID- 25127643 TI - Characterization of volatile components in four vegetable oils by headspace two dimensional comprehensive chromatography time-of-flight mass spectrometry. AB - Edible oil adulteration is the biggest source of food fraud all over the world. Since characteristic aroma is an important quality criterion for edible oils, we analyzed volatile organic compounds (VOCs) in four edible vegetable oils (soybean, peanut, rapeseed, and sunflower seed oils) by headspace comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (Headspace GC*GC-TOFMS) in this study. After qualitative and quantitative analysis of VOCs, we used unsupervised (PCA) and supervised (Random forests) multivariate statistical methods to build a classification model for the four edible oils. The results indicated that the four edible oils had their own characteristic VOCs, which could be used as markers to completely classify these four edible oils into four groups. PMID- 25127645 TI - Assessing oral bioaccessibility of trace elements in soils under worst-case scenarios by automated in-line dynamic extraction as a front end to inductively coupled plasma atomic emission spectrometry. AB - A novel biomimetic extraction procedure that allows for the in-line handing of >=400 mg solid substrates is herein proposed for automatic ascertainment of trace element (TE) bioaccessibility in soils under worst-case conditions as per recommendations of ISO norms. A unified bioaccessibility/BARGE method (UBM)-like physiological-based extraction test is evaluated for the first time in a dynamic format for accurate assessment of in-vitro bioaccessibility of Cr, Cu, Ni, Pb and Zn in forest and residential-garden soils by on-line coupling of a hybrid flow set-up to inductively coupled plasma atomic emission spectrometry. Three biologically relevant operational extraction modes mimicking: (i) gastric juice extraction alone; (ii) saliva and gastric juice composite in unidirectional flow extraction format and (iii) saliva and gastric juice composite in a recirculation mode were thoroughly investigated. The extraction profiles of the three configurations using digestive fluids were proven to fit a first order reaction kinetic model for estimating the maximum TE bioaccessibility, that is, the actual worst-case scenario in human risk assessment protocols. A full factorial design, in which the sample amount (400-800 mg), the extractant flow rate (0.5-1.5 mL min(-1)) and the extraction temperature (27-37 degrees C) were selected as variables for the multivariate optimization studies in order to obtain the maximum TE extractability. Two soils of varied physicochemical properties were analysed and no significant differences were found at the 0.05 significance level between the summation of leached concentrations of TE in gastric juice plus the residual fraction and the total concentration of the overall assayed metals determined by microwave digestion. These results showed the reliability and lack of bias (trueness) of the automatic biomimetic extraction approach using digestive juices. PMID- 25127646 TI - Chemometric processing of second-order liquid chromatographic data with UV-vis and fluorescence detection. A comparison of multivariate curve resolution and parallel factor analysis 2. AB - Second-order liquid chromatographic data with multivariate spectral (UV-vis or fluorescence) detection usually show changes in elution time profiles from sample to sample, causing a loss of trilinearity in the data. In order to analyze them with an appropriate model, the latter should permit a given component to have different time profiles in different samples. Two popular models in this regard are multivariate curve resolution-alternating least-squares (MCR-ALS) and parallel factor analysis 2 (PARAFAC2). The conditions to be fulfilled for successful application of the latter model are discussed on the basis of simple chromatographic concepts. An exhaustive analysis of the multivariate calibration models is carried out, employing both simulated and experimental chromatographic data sets. The latter involve the quantitation of benzimidazolic and carbamate pesticides in fruit and juice samples using liquid chromatography with diode array detection, and of polycyclic aromatic hydrocarbons in water samples, in both cases in the presence of potential interferents using liquid chromatography with fluorescence spectral detection, thereby achieving the second-order advantage. The overall results seem to favor MCR-ALS over PARAFAC2, especially in the presence of potential interferents. PMID- 25127647 TI - Electrochemical monitoring of intracellular enzyme activity of single living mammalian cells by using a double-mediator system. AB - We evaluated the intracellular NAD(P)H: quinone oxidoreductase (NQO) activity of single HeLa cells by using the menadione-ferrocyanide double-mediator system combined with scanning electrochemical microscopy (SECM). The double-mediator system was used to amplify the current response from the intracellular NQO activity and to reduce menadione-induced cell damage. The electron shuttle between the electrode and menadione was mediated by the ferrocyanide/ferricyanide redox couple. Generation of ferrocyanide was observed immediately after the addition of a lower concentration (10 MUM) of menadione. The ferrocyanide generation rate was constant for 120 min. At a higher menadione concentration (100 MUM), the ferrocyanide generation rate decreased within 30 min because of the cytotoxic effect of menadione. We also investigated the relationship between intracellular reactive oxygen species or glutathione levels and exposure to different menadione concentrations to determine the optimal condition for SECM with minimal invasiveness. The present study clearly demonstrates that SECM is useful for the analysis of intracellular enzymatic activities in single cells with a double-mediator system. PMID- 25127648 TI - Application of the diffusive gradients in thin films technique for available potassium measurement in agricultural soils: effects of competing cations on potassium uptake by the resin gel. AB - The utilization of Amberlite (IRP-69 ion-exchange resin, 100-500 wet mesh) as the binding phase in the diffusive gradients in thin films (DGT) technique has shown potential to improve the assessment of plant-available K in soils. The binding phase has recently been optimized by using a mixed Amberlite and ferrihydrite (MAF) gel which results in linear K uptake over extended deployment periods and in solutions with higher K concentrations. As restriction of K uptake by Ca on the Amberlite based resin gel has been previously proposed, potential competing effects of Ca(2+), Mg(2+) and NH(4+) on K uptake by the MAF gel were investigated. These cations had no effect on K elution efficiency which was 85%. However, K uptake by the MAF gel was restricted in the presence of competing cations in solution. Consequently, the diffusion coefficient of K decreased in the presence of cations compared to previous studies but was stable at 1.12*10( 5)cm(2)s(-1) at 25 degrees C regardless of cation concentrations. Uptake of K by the DGT device was affected by the presence of excessive Ca in more than 30% of twenty typical Australian agricultural soils. However, this problem could be circumvented by using a shorter deployment time than the normal 24 h. Moderate correlation of concentrations of K extracted by DGT with Colwell K (extracted by NaHCO(3), R(2)=0.69) and NH4OAc K (R(2)=0.61) indicates that DGT measures a different pool of K in soils than that measured by the standard extractants used. In addition, the MAF gel has the ability to measure Ca and Mg simultaneously. PMID- 25127644 TI - Associations of sleep disturbance with ADHD: implications for treatment. AB - Attention-deficit/hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep. The relationships of ADHD with sleep problems, psychiatric comorbidities and medications are complex and multidirectional. Evidence from published studies comparing sleep in individuals with ADHD with typically developing controls is most concordant for associations of ADHD with: hypopnea/apnea and peripheral limb movements in sleep or nocturnal motricity in polysomnographic studies; increased sleep onset latency and shorter sleep time in actigraphic studies; and bedtime resistance, difficulty with morning awakenings, sleep onset difficulties, sleep-disordered breathing, night awakenings and daytime sleepiness in subjective studies. ADHD is also frequently coincident with sleep disorders (obstructive sleep apnea, peripheral limb movement disorder, restless legs syndrome and circadian-rhythm sleep disorders). Psychostimulant medications are associated with disrupted or disturbed sleep, but also 'paradoxically' calm some patients with ADHD for sleep by alleviating their symptoms. Long-acting formulations may have insufficient duration of action, leading to symptom rebound at bedtime. Current guidelines recommend assessment of sleep disturbance during evaluation of ADHD, and before initiation of pharmacotherapy, with healthy sleep practices the first-line option for addressing sleep problems. This review aims to provide a comprehensive overview of the relationships between ADHD and sleep, and presents a conceptual model of the modes of interaction: ADHD may cause sleep problems as an intrinsic feature of the disorder; sleep problems may cause or mimic ADHD; ADHD and sleep problems may interact, with reciprocal causation and possible involvement of comorbidity; and ADHD and sleep problems may share a common underlying neurological etiology. PMID- 25127649 TI - The importance of chain length for the polyphosphate enhancement of acidic potassium permanganate chemiluminescence. AB - Sodium polyphosphate is commonly used to enhance chemiluminescence reactions with acidic potassium permanganate through a dual enhancement mechanism, but commercially available polyphosphates vary greatly in composition. We have examined the influence of polyphosphate composition and concentration on both the dual enhancement mechanism of chemiluminescence intensity and the stability of the reagent under analytically useful conditions. The average chain length (n) provides a convenient characterisation, but materials with similar values can exhibit markedly different distributions of phosphate oligomers. There is a minimum polyphosphate chain length (~6) required for a large enhancement of the emission intensity, but no further advantage was obtained using polyphosphate materials with much longer average chain lengths. Providing there is a sufficient average chain length, the optimum concentration of polyphosphate is dependent on the analyte and in some cases, may be lower than the quantities previously used in routine detection. However, the concentration of polyphosphate should not be lowered in permanganate reagents that have been partially reduced to form high concentrations of the key manganese(III) co-reactant, as this intermediate needs to be stabilised to prevent formation of insoluble manganese(IV). PMID- 25127650 TI - Absolute quantification of superoxide dismutase in cytosol and mitochondria of mice hepatic cells exposed to mercury by a novel metallomic approach. AB - In the last years, the development of new methods for analyzing accurate and precise individual metalloproteins is of increasing importance, since numerous metalloproteins are excellent biomarkers of oxidative stress and diseases. In that way, methods based on the use of post column isotopic dilution analysis (IDA) or enriched protein standards are required to obtain a sufficient degree of accuracy, precision and high limits of detection. This paper reports the identification and absolute quantification of Cu,Zn-superoxide dismutase (Cu,Zn SOD) in cytosol and mitochondria from mice hepatic cells using a innovative column switching analytical approach. The method consisted of orthogonal chromatographic systems coupled to inductively coupling plasma-mass spectrometry equipped with a octopole reaction systems (ICP-ORS-MS) and UV detectors: size exclusion fractionation (SEC) of the cytosolic and mitochondrial extracts followed by online anion exchange chromatographic (AEC) separation of Cu/Zn containing species. After purification, Cu,Zn-SOD was identified after tryptic digestion by molecular mass spectrometry (MS). The MS/MS spectrum of a doubly charged peptide was used to obtain the sequence of the protein using the MASCOT searching engine. This optimized methodology reduces the time of analysis and avoids the use of sample preconcentration and clean-up procedures, such as cut off centrifuged filters, solid phase extraction (SPE), precipitation procedures, off-line fractions insolates, etc. In this sense, the method is robust, reliable and fast with typical chromatographic run time less than 20 min. Precision in terms of relative standard deviation (n = 5) is of 3-5% and detection limits is 0.21 ngCug(-1). The application of the methodology to hepatic cells from mice exposed to inorganic mercury reveals decreased levels of Cu,Zn-SOD in cytosolic and mitochondrial extracts, as a consequence of the oxidative stress caused by this toxic metal. Additionally, the quantification of mitochondrial Cu,Zn-SOD in hepatic cells from Mus musculus has been carried out for the first time. PMID- 25127651 TI - In-situ vibrational optical rotatory dispersion of molecular organic crystals at high pressures. AB - Organic structures respond to pressure with a variety of mechanisms including degradation, intramolecular transformation and intermolecular bonding. The effects of pressure on chiral organic structures are of particular interest because of the potential steric controls on the fate of pressurized molecules. Despite representing a range of opportunities, the simultaneous study of high pressures on different forms of chiral structures is poorly explored. We have combined synchrotron-source vibrational optical rotatory dispersion, micro Fourier transform infrared spectroscopy and the use of a diamond anvil cell to simultaneously monitor the effects of pressure on the two enantiomers of the simple amino acid, alanine. PMID- 25127652 TI - Highly selective silver nanoparticles based label free colorimetric sensor for nitrite anions. AB - Highly selective label free colorimetric sensor based on AgNPs stabilized by phenolic chelating ligand, N,N'-bis(2-hydroxybenzyl)-1,2-diaminobenzene (1), for NO(2-) anions has been developed. Addition of NO(2-) showed selective decolourisation of brownish yellow colour of 1-AgNPs with the detection limit of 10(-7)M. Absorption studies showed the complete disappearance of 1-AgNPs peak at 426 nm due to the conversion of AgNPs to silver ions. The presence silver ions were confirmed by white precipitates of AgCl formation with NaCl. The interference studies confirmed the high selectivity of NO(2-) sensing in presence of anions as well as cations by 1-AgNPs. A linear relationship was observed between the change of absorption and concentration of NO(2-). The present approach could be performed at room temperature and ambient conditions. The practical applications of 1-AgNPs for selective sensing of NO(2-) in different water samples such as ground, river, pond and tap water have also been demonstrated. PMID- 25127653 TI - Magnetically assisted solid phase extraction using Fe3O4 nanoparticles combined with enhanced spectrofluorimetric detection for aflatoxin M1 determination in milk samples. AB - A novel, facile and inexpensive solid phase extraction (SPE) method using ethylene glycol bis-mercaptoacetate modified 3-(trimethoxysilyl)-1-propanethiol grafted Fe(3)O(4) nanoparticles coupled with spectrofluorimetric detection was proposed for determination of aflatoxin M1 (AFM1) in liquid milk samples. The method uses the advantage fluorescence enhancement by beta-cyclodexterin complexation of AFM1 in 12% (v/v) acetonitrile-water and the remarkable properties of Fe(3)O(4) nanoparticles namely high surface area and strong magnetization were utilized to achieve high enrichment factor (57) and satisfactory extraction recoveries (91-102%) using only 100 mg of magnetic adsorbent. Furthermore, fast separation time of about 15 min avoids many time consuming column-passing procedures of conventional SPE. The main factors affecting extraction efficiency including pH value, desorption conditions, extraction/desorption time, sample volume, and adsorbent amount were evaluated and optimized. Under the optimal conditions, a wide linear range of 0.04-8 ng mL( 1) with a low detection limit of 0.015 ng mL(-1) was obtained. The developed method was applied for extraction and preconcentration of AFM1 in three commercially available milk samples and the results were compared with the official AOAC method. PMID- 25127654 TI - Text recycling: acceptable or misconduct? AB - Text recycling, also referred to as self-plagiarism, is the reproduction of an author's own text from a previous publication in a new publication. Opinions on the acceptability of this practice vary, with some viewing it as acceptable and efficient, and others as misleading and unacceptable. In light of the lack of consensus, journal editors often have difficulty deciding how to act upon the discovery of text recycling. In response to these difficulties, we have created a set of guidelines for journal editors on how to deal with text recycling. In this editorial, we discuss some of the challenges of developing these guidelines, and how authors can avoid undisclosed text recycling. PMID- 25127655 TI - Reduced-dose warfarin or interrupted warfarin with heparin bridging for pacemaker or defibrillator implantation: a randomized trial. AB - BACKGROUND: Perioperative management with reduced-dose warfarin is of potential interest by eliminating the need for bridging while still maintaining a degree of anticoagulation. The outcomes of this regimen have not been well determined. METHODS: In a randomized controlled trial we compared two regimens for management of anticoagulation with warfarin in patients with implantation of a pacemaker or defibrillator. Half dose of warfarin for 3-6 days, depending on the baseline international normalized ratio (INR), before surgery aiming at an INR of <= 1.7 was compared with interrupted warfarin for 5 days with preoperative bridging with low-molecular-weight heparin (LMWH) at therapeutic dose for 2.5 days. Main safety outcome was pocket hematoma. Secondary outcomes were major bleeding, thromboembolism - all within 1 month, days of hospitalization and number of patients requiring correction of INR with vitamin K. RESULTS: The study was planned for 450 patients but it was discontinued prematurely due to a change in practice. Pocket hematoma occurred in 4 of 85 patients (5%) randomized to the bridged regimen and in 3 of 86 patients (3%) randomized to reduced-dose warfarin. One pocket hematoma in each group was severe. There were no major hemorrhages or thromboembolism within the 1-month window. Duration of hospitalization was similar in the two groups. Correction of INR the day before surgery with vitamin K had to be used for significantly more patients in the reduced-dose warfarin group (41%) than in the bridged regimen group (6%). CONCLUSION: The reduced-dose warfarin regimen appeared to have similar safety after device implantation as interrupted warfarin with preoperative LMWH bridging. Due to premature discontinuation no firm conclusion can be drawn. The reduced-dose warfarin regimen often failed to achieve the intended preoperative INR. ClinicalTrials.gov Identifier: NCT 02094157. PMID- 25127656 TI - Pharmacokinetics of vancomycin in critically ill patients undergoing continuous venovenous haemodialysis. PMID- 25127658 TI - The geostatistic-based spatial distribution variations of soil salts under long term wastewater irrigation. AB - The purpose of this study was to determine and evaluate the spatial changes in soil salinity by using geostatistical methods. The study focused on the suburb area of Beijing, where urban development led to water shortage and accelerated wastewater reuse to farm irrigation for more than 30 years. The data were then processed by GIS using three different interpolation techniques of ordinary kriging (OK), disjunctive kriging (DK), and universal kriging (UK). The normality test and overall trend analysis were applied for each interpolation technique to select the best fitted model for soil parameters. Results showed that OK was suitable for soil sodium adsorption ratio (SAR) and Na(+) interpolation; UK was suitable for soil Cl(-) and pH; DK was suitable for soil Ca(2+). The nugget-to sill ratio was applied to evaluate the effects of structural and stochastic factors. The maps showed that the areas of non-saline soil and slight salinity soil accounted for 6.39 and 93.61%, respectively. The spatial distribution and accumulation of soil salt were significantly affected by the irrigation probabilities and drainage situation under long-term wastewater irrigation. PMID- 25127659 TI - Palonosetron versus ondansetron as rescue medication for postoperative nausea and vomiting: a randomized, multicenter, open-label study. AB - BACKGROUND: This study compared palonosetron and ondansetron as rescue medications for postoperative nausea and vomiting (PONV) in patients who received prophylactic ondansetron. Although guidelines recommend use of an agent from a different class when prophylaxis has failed, palonosetron has unique properties relative to other serotonin 5-HT3 receptor antagonists. Prior trials assessing its use for rescue have had conflicting results. Although palonosetron has compared favorably with ondansetron for PONV prevention, the drugs have not been compared in the rescue setting of failure of 5-HT3 receptor antagonist prophylaxis. METHODS: This was a randomized, open-label, multicenter trial comparing the efficacy and safety of intravenous palonosetron 0.075 mg and intravenous ondansetron 4 mg in patients experiencing PONV following laparoscopic abdominal or gynecological surgery despite prophylactic ondansetron. RESULTS: Of 239 patients screened, 220 were enrolled and 98 were treated for PONV: 48 and 50 in the palonosetron and ondansetron arms, respectively. Complete control during 72 hours after study drug administration was achieved in 25.0% of palonosetron recipients and 18.0% of ondansetron recipients (95% confidence interval [CI], 9.2, 23.3; p = 0.40). Corresponding incidences of vomiting were 29.2% for palonosetron and 48.0% for ondansetron (95% CI, -0.06, 37.7; p = 0.057), and 62.5% and 56.0% required additional rescue treatment, respectively (95% CI, 25.9, 12.9; p = 0.52). Other than a similar incidence of procedural pain in the 2 groups, the most common treatment-emergent adverse events, which were generally mild, were headache (14.6% vs 12.0%), constipation (8.3% vs 10.0%), and dizziness (6.3% vs 8.0%), for the palonosetron and ondansetron groups, respectively. CONCLUSIONS: Palonosetron and ondansetron did not show differences in the primary efficacy endpoint of CC during the 72 hours after study drug administration. There was a trend toward less emesis in the 0-72 h time period favoring palonosetron. While larger studies are needed to fully assess any clinical benefits of palonosetron to rescue patients who have failed ondansetron prophylaxis for PONV, the benefit, if any, would be limited based on this study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00967499 (Registered August 27, 2009). PMID- 25127657 TI - Novel self assembling nanoparticles for the oral administration of fondaparinux: synthesis, characterization and in vivo evaluation. AB - Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and medium-term thromboembolic disease. To overcome the low oral bioavailability of Fpx, a new nanoparticulate carrier has been developed. The nanoparticles (NPs) contain squalenyl derivatives, known for their excellent oral bioavailability. They spontaneously self-assemble upon both electrostatic and hydrophobic interactions between the polyanionic Fpx and cationic squalenyl (CSq) derivatives. The preparation conditions were optimized to obtain monodisperse, stable NPs with a mean diameter in the range of 150-200 nm. The encapsulation efficiencies were around 80%. Fpx loadings reached 39 wt.%. According to structural and morphological analysis, Fpx and CSq organized in spherical multilamellar ("onion-type") nanoparticles. Furthermore, in vivo studies in rats suggested that Fpx was well absorbed from the orally administered NPs, which totally dissociated when reaching the blood stream, leading to the release of free Fpx. The Fpx:CSq NPs improved the plasmatic concentration of Fpx in a dose dependent manner. However, the oral bioavailability of these new NPs remained low (around 0.3%) but of note, the Cmax obtained after oral administration of 50mg/kg NPs was close to the prophylactic plasma concentration needed to treat venous thromboembolism. Moreover, the oral bioavailability of Fpx could be dramatically increased up to 9% by including the nanoparticles into gastroresistant capsules. This study opens up new perspectives for the oral administration of Fpx and paves the way towards elaborating squalene-based NPs which self assemble without the need of covalently grafting the drug to Sq. PMID- 25127660 TI - Plasmalogens in the retina: from occurrence in retinal cell membranes to potential involvement in pathophysiology of retinal diseases. AB - Plasmalogens (Pls) represent a specific subclass of glycerophospholipids characterized by the presence of a vinyl-ether bond at the sn-1 position of glycerol. Pls are quantitatively important in membranes of neuronal tissues, including the brain and the retina, where they can represent until almost two third of ethanolamine glycerophospholipids. They are considered as reservoirs of polyunsaturated fatty acids as several studies have shown that arachidonic and docosahexaenoic acids are preferentially esterified on Pls when compared to other glycerophospholipids. Reduced levels of Pls were observed in a number of neurodegenerative disorders such as glaucoma, the second leading cause of blindness worldwide. In a mouse model of Pls deficiency, "glaucoma-like" optic nerve abnormalities were observed as well as developmental defects in the eye. These included microphthalmia, dysgenesis of the anterior segment of the eye, and abnormalities in retinal vessel architecture. Several data from animal and in vitro studies suggest that Pls may be involved in the regulation of retinal vascular development through the release of polyunsaturated fatty acids by a calcium-independent phospholipase A2. PMID- 25127661 TI - Critical roles of DNase1l3l in lens nuclear degeneration in zebrafish. AB - The vertebrate lens undergoes organelle and nuclear degradation during lens development, allowing the lens to become transparent. DNase2b is an enzyme responsible for nuclear degradation in the mouse lens; however, dnase2b expression in zebrafish showed a distribution pattern that differed from that in mice. No zebrafish dnase2b was detected by reverse-transcription polymerase chain reaction until around 120 h postfertilization (hpf), suggesting that dnase2b is not expressed in the critical period for lens nuclear degradation, which corresponds to 56-74 hpf. However, public database searches have indicated that dnase1l3l is strongly and specifically expressed in embryonic zebrafish lens. Whole mount in situ hybridization showed that dnase1l3l expression began around 36 hpf and was found exclusively in the lens until the adult stage. Morpholino (MO)-dependent downregulation of dnase1l3l expression during early development in zebrafish led to the failure of nuclear degradation in the lens. Immunostaining of lens sections showed that expression of Pax6, Prox1 and beta-catenin was comparable to the control in the early stage of development in dnase1l3l-MO injected embryos. However, downregulation of expression of these genes in lens was not observed in dnase1l3l-MO-treated zebrafish at 72 hpf, suggesting that the lens development was halted. Taken together, we showed that dnase1l3l plays major roles in nuclear degradation in zebrafish lens development. No homologous gene was found in other species in public databases, suggesting that dnase1l3l developed and acquired its function specifically in zebrafish. PMID- 25127662 TI - Women's participation in breast cancer screening in France--an ethical approach. AB - BACKGROUND: Breast cancer is a major public health challenge. Organized mammography screening (OS) is considered one way to reduce breast cancer mortality. EU recommendations prone mass deployment of OS, and back in 2004, France introduced a national OS programme for women aged 50-74 years. However, in 2012, participation rate was still just 52.7%, well short of the targeted 70% objective. In an effort to re-address the (in) efficiency of the programme, the French National Cancer Institute has drafted an expert-group review of the ethical issues surrounding breast cancer mammography screening. DISCUSSION: Prompted by emerging debate over the efficiency of the screening scheme and its allied public information provision, we keynote the experts' report based on analysis of epidemiological data and participation rate from the public health authorities. The low coverage of the OS scheme may be partly explained by the fact that a significant number of women undergo mammography outside OS and thus outside OS criteria. These findings call for further thinking on (i) the ethical principles of beneficence and non-malfeasance underpinning this public health initiative, (ii) the reasons behind women's and professionals' behavior, and (iii) the need to analyze how information provision to women and the doctor patient relationship need to evolve in response to scientific controversy over the risks and benefits of conducting mammographic screening. SUMMARY: This work calls for a reappraisal of the provision of screening programme information. We advocate a move to integrate the points sparking debate over the efficiency of the screening scheme to guarantee full transparency. The perspective is to strengthen the respect for autonomy allowing women to make an informed choice in their decision on whether or not to participate. PMID- 25127664 TI - Estimating prevalence and burden of major disorders of the brain in Nepal: cultural, geographic, logistic and philosophical issues of methodology. AB - BACKGROUND: Headache, anxiety and depression are major disorders of the brain in terms of their prevalence and the burdens and costs they impose on society. Nationwide population-based studies of these disorders are necessary to inform health policy but, in research-naive and resource-poor countries such as Nepal, a host of methodological problems are encountered: cultural, geographic, logistic and philosophical. METHODS: Expert consensus was sought among researchers from different professional and cultural backgrounds in planning and conceptualizing an epidemiological study and adapting established methods to the special situation and circumstances of Nepal. RESULTS: The methodological problems were sorted into different themes: study design; climate; geography, access and transport; sociocultural issues; safety of interviewers. Each of these was dealt with separately, and their inter-relationships explored, in finding solutions that were sometimes pragmatic. A cross-sectional questionnaire-based study, with teams of interviewers visiting households across the three physiographic divisions (with extremes in altitude) in each of the five development regions of the country, would enable national sampling with sociocultural representativeness. However, the study instruments and interviews would be in Nepali only. Transport and access challenges were considerable, and their solutions combined travel by air, bus, river and foot, with allowances for rain damaged roads, collapsed bridges and cancelled scheduled flights. The monsoon would render many routes impassable, and therefore set an absolute time limitation. Engaging participants willingly in the enquiry would be the key to success, and several tactics would be employed to enhance the success of this, most importantly enlisting the support of local community volunteers in each study site. CONCLUSION: Anticipating problems in advance of investing substantial resources in a large nationwide epidemiological study in Nepal was a sensible precaution. The difficulties could be resolved or circumvented without expected compromise in scientific quality. Expert consensus was an effective means of achieving this outcome. PMID- 25127663 TI - Phenethyl isothiocyanate upregulates death receptors 4 and 5 and inhibits proliferation in human cancer stem-like cells. AB - BACKGROUND: The cytokine TRAIL (tumor necrotic factor-related apoptosis-inducing ligand) selectively induces apoptosis in cancer cells, but cancer stem cells (CSCs) that contribute to cancer-recurrence are frequently TRAIL-resistant. Here we examined hitherto unknown effects of the dietary anti-carcinogenic compound phenethyl isothiocyanate (PEITC) on attenuation of proliferation and tumorigenicity and on up regulation of death receptors and apoptosis in human cervical CSC. METHODS: Cancer stem-like cells were enriched from human cervical HeLa cell line by sphere-culture method and were characterized by CSC-specific markers' analyses (flow cytometry) and Hoechst staining. Cell proliferation assays, immunoblotting, and flow cytometry were used to assess anti-proliferative as well as pro-apoptotic effects of PEITC exposure in HeLa CSCs (hCSCs). Xenotransplantation study in a non-obese diabetic, severe combined immunodeficient (NOD/SCID) mouse model, histopathology, and ELISA techniques were further utilized to validate our results in vivo. RESULTS: PEITC attenuated proliferation of CD44(high/+)/CD24(low/-), stem-like, sphere-forming subpopulations of hCSCs in a concentration- and time-dependent manner that was comparable to the CSC antagonist salinomycin. PEITC exposure-associated up regulation of cPARP (apoptosis-associated cleaved poly [ADP-ribose] polymerase) levels and induction of DR4 and DR5 (death receptor 4 and 5) of TRAIL signaling were observed. Xenotransplantation of hCSCs into mice resulted in greater tumorigenicity than HeLa cells, which was diminished along with serum hVEGF-A (human vascular endothelial growth factor A) levels in the PEITC-pretreated hCSC group. Lung metastasis was observed only in the hCSC-injected group that did not receive PEITC-pretreatment. CONCLUSIONS: The anti-proliferative effects of PEITC in hCSCs may at least partially result from up regulation of DR4 and possibly DR5 of TRAIL-mediated apoptotic pathways. PEITC may offer a novel approach for improving therapeutic outcomes in cancer patients. PMID- 25127665 TI - Plasma and platelet serotonin concentrations in healthy dogs and dogs with myxomatous mitral valve disease. AB - OBJECTIVES: Serotonin has been implicated in canine myxomatous mitral valve disease (MMVD); however, the sources of serotonin have not been fully elucidated. This study compared the concentration of serotonin in plasma and platelets of normal healthy small breed dogs with predisposition to MMVD and dogs with naturally occurring MMVD. ANIMALS: 43 small-breed client-owned dogs with an approximate weight of <10 kg and age of 6 years or above were divided into 2 groups: a healthy control group (n = 20) and a group with echocardiographic evidence of MMVD (n = 23). METHODS: 5 ml samples of blood were collected. Plasma and platelets were separated by centrifugation and assayed for serotonin measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Median plasma serotonin concentration was not significantly different (p = 0.3630) between normal healthy dogs (3.7 ng/ml) and dogs with MMVD (4.3 ng/ml). Males had higher plasma serotonin concentration than females (4.7 and 2.9 ng/ml respectively, p = 0.0043). Platelet serotonin concentration was not different between healthy dogs and dogs with MMVD (128.6 ng/109 platelets and 176.6 ng/109 platelets respectively, p = 0.4575). Age, echocardiographic indices and platelet count showed no correlation with plasma or platelet serotonin concentration. CONCLUSIONS: Circulating plasma serotonin is unlikely a major source of serotonin signaling in canine MMVD. Platelets could be a source of serotonin in canine MMVD through platelet adhesion to the mitral valve; however, the amount of serotonin stored in platelets of healthy dogs and dogs with MMVD is not different. PMID- 25127666 TI - Echocardiographic and radiographic findings in a cohort of healthy adult green iguanas (Iguana iguana). AB - OBJECTIVES: To describe characteristics of echocardiography and cranial coelomic radiography in a cohort of iguanas. ANIMALS: Twenty apparently healthy adult green iguanas (Iguana iguana) from a reptile sanctuary. METHODS: Physical examination, radiography, two-dimensional and color Doppler echocardiography were performed to assess cardiac structures and function, and any related normal or abnormal findings were recorded. RESULTS: Echocardiographic examination was possible without sedation and allowed visualization of the great vessels, atria, and ventricle. Some structures could not be evaluated in a minority of the iguanas due to individual differences in bony conformation and imaging quality. Suspected abnormal echocardiographic findings in 3 iguanas included pericardial effusion (n = 1) and enlarged caudal vena cava and/or sinus venosus (n = 2). Objective measurements were repeatable as assessed by within-subject coefficient of variation, and reliable as assessed by intra-observer intraclass correlation coefficient. Left atrial and ventricular measurements were significantly correlated with body weight. Valve regurgitation was common, with atrioventricular valve regurgitation present in 53% (9/17) and aortic or pulmonic valve regurgitation in 71% (12/17) of otherwise normal iguanas. A heart murmur was not appreciated during examination of any of the iguanas. Heart size cannot be measured radiographically due to superimposition and silhouetting of other coelomic structures. Echocardiographic or radiographic findings consistent with mineralization of the great vessels were present in 76% of iguanas (13/17). CONCLUSIONS: Echocardiography in iguanas is well tolerated without sedation and allowed both subjective evaluation and structural measurements. Valve regurgitation and great vessel mineralization were commonly observed in this cohort of apparently healthy adult iguanas. PMID- 25127667 TI - The effects of health coaching on adult patients with chronic diseases: a systematic review. AB - OBJECTIVE: The aim of this systematic review was to describe the effects of health coaching on adult patients with chronic diseases. METHODS: The reviewers searched electronic databases and performed a manual search for studies published from 2009 to 2013. The inclusion criteria covered health coaching for adults with chronic diseases by health care professionals. The studies were original, randomized controlled trials or quasi-experimental designs. RESULTS: Thirteen studies were selected using the inclusion criteria. The results indicate that health coaching produces positive effects on patients' physiological, behavioral and psychological conditions and on their social life. In particular, statistically significant results revealed better weight management, increased physical activity and improved physical and mental health status. CONCLUSION: Health coaching improves the management of chronic diseases. Further research into the cost-effectiveness of health coaching and its long-term effectiveness for chronic diseases is needed. Practice implications Health care professionals play key roles in promoting healthy behavior and motivating good care for adults with chronic diseases. Health coaching is an effective patient education method that can be used to motivate and take advantage of a patient's willingness to change their life style and to support the patient's home-based self-care. PMID- 25127668 TI - Delayed left ventricular apical thrombus formation following discontinuation of dual anti-platelet therapy. AB - Delayed de novo left ventricular apical thrombus following a distant antero apical myocardial infarction has to our knowledge not been previously reported. Herein we describe a patient who developed an apical thrombus 18 months after his initial infarct following cessation of dual anti-platelet therapy for a traumatic subdural haematoma requiring surgical evacuation. PMID- 25127669 TI - Cardiac vignette: isolated pulmonary regurgitation. AB - Isolated pulmonary regurgitation (PR) is a rare occurrence with only a handful of documented cases worldwide. Though usually well tolerated in childhood, chronic PR can eventually lead to RV dysfunction and ventricular arrhythmias. In this cardiac vignette, we describe a case of isolated PR in a young female presenting with syncope and explore the natural history, different investigative modalities as well as issues in clinical management of this rare condition. PMID- 25127670 TI - Mitochondrial DNA has three major variations. PMID- 25127671 TI - Molecular cloning, characterization and tissue distribution of two ostrich beta defensins: AvBD2 and AvBD7. AB - Avian beta-defensins (AvBDs) are a family of small antimicrobial peptides that play important roles in the innate immunity of birds. Herein, we report on two new ostrich AvBD genes, AvBD2 and AvBD7, which were isolated from the bone marrow of ostriches (Struthio camelus). The coding regions of ostrich AvBD2 and AvBD7 comprised 195 bp and 201bp, which encoded 64 and 66 amino acids, respectively. Homology analysis showed that ostrich AvBD2 had the highest similarity (up to 86%) with the swan goose (Anser cygnoides) AvBD2, while ostrich AvBD7 shared the highest similarity (up to 81%) with chicken AvBD7. Analysis of the codon-usage bias showed that the two ostrich AvBDs had different codon-usage patterns from other AvBDs. The two synthetic AvBD peptides exhibited antibacterial activities against both Gram-positive and Gram-negative bacteria, and these activities decreased significantly in the presence of 100mM NaCl (P<0.01). Real-time reverse transcription-polymerase chain reaction analysis showed that AvBD2 and AvBD7 were widely expressed at different levels in 17 different tissues. This is the first report of the nucleotide sequences of ostrich AvBDs. Further investigations of these two AvBDs may help us to gain new insights into the immune defense system of the ostrich and to make subsequent therapeutic use of ostrich defensins. PMID- 25127672 TI - Double incretin receptor knock-out (DIRKO) mice present with alterations of trabecular and cortical micromorphology and bone strength. AB - A role for gut hormone in bone physiology has been suspected. We evidenced alterations of microstructural morphology (trabecular and cortical) and bone strength (both at the whole-bone--and tissue-level) in double incretin receptor knock-out (DIRKO) mice as compared to wild-type littermates. These results support a role for gut hormones in bone physiology. INTRODUCTION: The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), have been shown to control bone remodeling and strength. However, lessons from single incretin receptor knock-out mice highlighted a compensatory mechanism induced by elevated sensitivity to the other gut hormone. As such, it is unclear whether the bone alterations observed in GIP or GLP-1 receptor deficient animals resulted from the lack of a functional gut hormone receptor, or by higher sensitivity for the other gut hormone. The aims of the present study were to investigate the bone microstructural morphology, as well as bone tissue properties, in double incretin receptor knock-out (DIRKO) mice. METHODS: Twenty-six-week-old DIRKO mice were age- and sex-matched with wild-type (WT) littermates. Bone microstructural morphology was assessed at the femur by microCT and quantitative X-ray imaging, while tissue properties were investigated by quantitative backscattered electron imaging and Fourier-transformed infrared microscopy. Bone mechanical response was assessed at the whole-bone- and tissue level by 3-point bending and nanoindentation, respectively. RESULTS: As compared to WT animals, DIRKO mice presented significant augmentations in trabecular bone mass and trabecular number whereas bone outer diameter, cortical thickness, and cortical area were reduced. At the whole-bone-level, yield stress, ultimate stress, and post-yield work to fracture were significantly reduced in DIRKO animals. At the tissue-level, only collagen maturity was reduced by 9 % in DIRKO mice leading to reductions in maximum load, hardness, and dissipated energy. CONCLUSIONS: This study demonstrated the critical role of gut hormones in controlling bone microstructural morphology and tissue properties. PMID- 25127673 TI - A systematic review of complicated diverticulitis in post-transplant patients. AB - BACKGROUND: Immunosuppression could increase the complication rate in patients with acute diverticulitis. This would justify a low threshold for elective sigmoid resection in these patients after an episode of diverticulitis. Well documented groups of immunocompromised patients are transplant patients, in which many prospective studies have been conducted. OBJECTIVES: The aim of this systematic review is to assess the incidence of complicated diverticulitis in post-transplant patients. DATA SOURCE: We searched MEDLINE, EMBASE, CINAHL, and Cochrane databases for papers published between January 1966 and January 2014. STUDY SELECTION AND INTERVENTION: Publications dealing with post-transplant patients and left-sided diverticulitis were eligible for inclusion. The following exclusion criteria were used for study selection: abstracts, case-series and non English articles. MAIN OUTCOME MEASURES: Primary outcome measure was the incidence of complicated diverticulitis. Secondary outcome was the incidence of acute diverticulitis and the proportion of complicated diverticulitis. Pooling of data was only performed when more than five reported on the outcome of interest with comparable cohorts. Only studies describing proportion of complicated diverticulitis and renal transplant studies were eligible for pooling data. RESULTS: Seventeen articles met the inclusion criteria. Nine renal transplant cohorts, four mixed lung-heart-heart lung transplant cohorts, two heart transplant cohorts, and two lung cohorts. A total of 11,966 post-transplant patients were included in the present review. Overall incidence of complicated diverticulitis in all transplantation studies ranged from 0.1 to 3.5%. Nine studies only included renal transplant patients. Pooled incidence of complicated diverticulitis in these patients was 1.0% (95% CI 0.6 to 1.5%). Ten studies provided proportion of complicated diverticulitis. Pooled incidence of acute diverticulitis in these studies was 1.7% (95% CI 1.0 to 2.7%). Pooled proportion of complicated diverticulitis among these patients was 40.1% (95% CI 32.2 to 49.7%). All studies were of moderate quality using the MINORS scoring scale. CONCLUSION: The incidence of complicated diverticulitis is about one in 100 transplant patients. Additionally when a transplant patient develops an episode of acute diverticulitis, a high proportion of patients have a complicated disease course. PMID- 25127674 TI - Changes in the loading conditions induced by vagal stimulation modify the myocardial infarct size through sympathetic-parasympathetic interactions. AB - In a previous research, we described that vagal stimulation increases the infarct size by sympathetic co-activation. The aim of this study was to determine if hemodynamic changes secondary to the vagal stimulation are able to activate sympathetic compensatory neural reflexes, responsible for increasing the infarct size. A second goal was to determine if intermittent vagal stimulation avoids sympathetic activation and reduces infarct size by muscarinic activation of the Akt/glycogen synthase kinase 3 beta (GSK-3beta) pathway. Rabbits were subjected to 30 min of regional myocardial ischemia and 3 h of reperfusion without vagal stimulation, or the following protocols of right vagus nerve stimulation for 10 min before ischemia: (a) continuous vagal stimulation and (b) intermittent vagal stimulation (cycles of 10 s ON/50 s OFF). Continuous vagal stimulation increased the infarct size (70.7 +/- 4.3 %), even after right vagal section (68.6 +/- 4.1 %) compared with control group (52.0 +/- 3.7 %, p < 0.05). Bilateral vagotomy, pacing, and esmolol abolished the deleterious effect, reaching an infarct size of 43.3 +/- 5.1, 43.5 +/- 2.1, and 46.0 +/- 4.6 % (p < 0.05), respectively. Intermittent stimulation reduced the infarct size to 29.8 +/- 3.0 % (p < 0.05 vs I/R). This effect was blocked with atropine (50.2 +/- 3.6 %, p < 0.05). Continuous vagal stimulation induced bradycardia and increased the loading conditions and wall stretching of the atria. These changes provoked the co activation reflex of the sympathetic nervous system, observed by the rise in plasmatic catecholamine levels, which increased the infarct size. Sympathetic co activation was abolished by continuous vagal stimulation with constant heart rate or parasympathetic deafferentation. Intermittent vagal stimulation attenuated the sympathetic tone and reduced the infarct size by the muscarinic activation of the Akt pathway and GSK-3beta inhibition. Continuous stimulation only phosphorylated Akt and GSK-3beta when esmolol was administered. PMID- 25127676 TI - An effector gene hopA1 influences on virulence, host specificity, and lifestyles of Pseudomonas cichorii JBC1. AB - Pseudomonas cichorii is a devastating pathogen which infects a wide range of ornamental as well as agricultural crops worldwide. Characterization of virulence genes helps to understand pathogens' infection processes, which may lead to development of resistant crops. For functional validation of novel genes, we re constructed pUCP18 vector with lambda phage red operon and sacB gene (pUCP18_RedS), which simplified conventional marker exchange system. The effector gene hopA1 of P. cichorii JBC1 was marker exchanged with PCR product of kanamycin gene flanked by hopA1 flanking region using pUCP18_RedS. The virulence and internal growth of hopA1 defective mutant (DeltahopA1) in tomato seedlings was significantly reduced compared to wild type (WT) and hopA1 complemented strain (DeltahopA1::phopA1). The analysis on role of hopA1 in host range revealed that P. cichorii was hopA1-dependent to infect cabbage, tomato, soybean, hot pepper, and cucumber, but not melon and eggplant. Despite the similarity in growth pattern, the biofilm formation and swarming motility of DeltahopA1 were significantly reduced compared to WT and DeltahopA1::phopA1. The results of this study indicate that hopA1 plays a significant role not only in virulence and host specificity, but also motility and biofilm formation of P. cichorii which may influence the infection processes. PMID- 25127675 TI - Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1. AB - Potassium channels comprise the apical leak pathway supplying extracellular K(+) for exchange with protons by the gastric H(+), K(+)-ATPase and provide potential therapeutic targets for inhibiting gastric acid secretion. The Kir1.1 (ROMK) potassium channel mediates the high capacity K(+) recycling necessary for NaCl reabsorption in the thick ascending limb of the kidney, and this channel exhibits functional and regulatory characteristic well suited for K(+) recycling by gastric parietal cells. We report here that Kir1.1 channels are required for gastric acid secretion and that this channel participates with Kv7.1 (KCNQ1/KvLQT1) in the potassium recycling process. We show that Kir1.1 colocalizes with the beta-subunit of H(+), K(+)-ATPase in gastric parietal cells of Kir1.1 wild-type mice. In Kir1.1-deficient mice, gastric mucosal morphology, as well as parietal cell number, proliferation index, and ultrastructure were normal but secretagogue-stimulated gastric acid secretion in whole stomach and perfused gastric glands was absent. Luminal application of potassium-restored acid secretion in perfused gastric glands from Kir1.1-deficient as well as barium blocked wild-type mice. In wild-type mice, both luminal Tertiapin-Q, an inhibitor of Kir1.1, as well as XE991, an inhibitor of Kv7.1, reduced proton secretion. We propose that Kir1.1 and Kv7.1 channels collaborate in potassium and current recycling across the apical pole of parietal cells. PMID- 25127678 TI - Converging goals of treatment of inflammatory bowel disease from clinical trials and practice. AB - It is important to have clear goals for treating inflammatory bowel disease in clinical practice and in research. Conventional end points for trials in ulcerative colitis and Crohn's disease have been based on composite indices, such as the Mayo Clinic Score and the Crohn's Disease Activity Index; these indices incorporate symptoms, signs, and findings from laboratory tests and sometimes endoscopic assessments. Although definitions of clinical response and remission have been based on these indices for regulatory purposes, they are difficult to apply to practice because they are complex and not intuitive to clinicians. This has caused a disconnect between clinical trials and practice. Recently, the use of composite indices in trials has been reevaluated in Food and Drug Administration-sponsored Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics workshops due to concerns about the validity of the indices. Alternative measures of outcome and definitions of response are being developed. Patient-reported outcomes are psychometric instruments created and defined by patients to quantify symptoms. A combination of end points, comprising patient-reported outcomes and objective evaluation of inflammation by endoscopy, offers a clinically meaningful and scientifically valid alternative to existing composite indices. Unlike composite indices, response definitions based on endoscopy and patient-reported outcomes can be readily applied in practice. This convergence of outcome assessment in clinical trials and practice could expedite implementation of "treat-to-target" algorithms, in which therapy is progressively intensified until a specific treatment goal is reached. This approach could improve patient care by reducing rates of disease-related complications, surgery, and hospitalization. PMID- 25127677 TI - Nicotine promotes initiation and progression of KRAS-induced pancreatic cancer via Gata6-dependent dedifferentiation of acinar cells in mice. AB - BACKGROUND & AIMS: Although smoking is a leading risk factor for pancreatic ductal adenocarcinoma (PDAC), little is known about the mechanisms by which smoking promotes initiation or progression of PDAC. METHODS: We studied the effects of nicotine administration on pancreatic cancer development in Kras(+/LSLG12Vgeo);Elas-tTA/tetO-Cre (Ela-KRAS) mice, Kras(+/LSLG12D);Trp53+/LSLR172H;Pdx-1-Cre (KPC) mice (which express constitutively active forms of KRAS), and C57/B6 mice. Mice were given nicotine for up to 86 weeks to produce blood levels comparable with those of intermediate smokers. Pancreatic tissues were collected and analyzed by immunohistochemistry and reverse transcriptase polymerase chain reaction; cells were isolated and assayed for colony and sphere formation and gene expression. The effects of nicotine were also evaluated in primary pancreatic acinar cells isolated from wild-type, nAChR7a(-/-), Trp53(-/-), and Gata6(-/-);Trp53(-/-) mice. We also analyzed primary PDAC cells that overexpressed GATA6 from lentiviral expression vectors. RESULTS: Administration of nicotine accelerated transformation of pancreatic cells and tumor formation in Ela-KRAS and KPC mice. Nicotine induced dedifferentiation of acinar cells by activating AKT-ERK-MYC signaling; this led to inhibition of Gata6 promoter activity, loss of GATA6 protein, and subsequent loss of acinar differentiation and hyperactivation of oncogenic KRAS. Nicotine also promoted aggressiveness of established tumors as well as the epithelial mesenchymal transition, increasing numbers of circulating cancer cells and their dissemination to the liver, compared with mice not exposed to nicotine. Nicotine induced pancreatic cells to acquire gene expression patterns and functional characteristics of cancer stem cells. These effects were markedly attenuated in K Ras(+/LSL-G12D);Trp53(+/LSLR172H);Pdx-1-Cre mice given metformin. Metformin prevented nicotine-induced pancreatic carcinogenesis and tumor growth by up regulating GATA6 and promoting differentiation toward an acinar cell program. CONCLUSIONS: In mice, nicotine promotes pancreatic carcinogenesis and tumor development via down-regulation of Gata6 to induce acinar cell dedifferentiation. PMID- 25127679 TI - Equivalency of fecal immunochemical tests and colonoscopy in familial colorectal cancer screening. AB - BACKGROUND & AIMS: Colonoscopy is the recommended screening procedure for first degree relatives of patients with colorectal cancer (CRC), but few studies have compared its efficacy for CRC detection with that of other screening strategies. We conducted a controlled randomized trial to compare the efficacy of repeated fecal immunochemical tests (FITs) and colonoscopy in detecting advanced neoplasia (advanced adenoma or CRC) in family members of patients with CRC. METHODS: In a prospective study, 1918 first-degree relatives of patients with CRC were randomly assigned (1:1 ratio) to receive a single colonoscopy examination or 3 FITs (1/year for 3 years; OC-Sensor; cutoff >=10 MUg hemoglobin/g feces, corresponding to 50 ng hemoglobin/mL buffer). The strategies were considered to be equivalent if the 95% confidence interval of the difference for the detection of advanced neoplasia was +/-3%. Follow-up analyses were performed to identify false-negative FIT results and interval CRCs. RESULTS: Of all eligible asymptomatic first-degree relatives, 782 were included in the colonoscopy group and 784 in the FIT group. In the intention-to-screen analysis, advanced neoplasia was detected in 33 (4.2%) and 44 (5.6%) first-degree relatives in the FIT and colonoscopy groups, respectively (odds ratio = 1.41; 95% confidence interval: 0.88-2.26; P = .14). In the per-protocol analysis, 28 first-degree relatives (3.9%) in the FIT group and 43 (5.8%) in the colonoscopy group had advanced neoplasia (odds ratio = 1.56; 95% confidence interval: 0.95-2.56; P = .08). FIT missed 16 of 41 advanced adenomas but no CRCs. The FIT strategy required endoscopic evaluation of 4-fold fewer individuals to detect 1 advanced neoplasia than the colonoscopy strategy. CONCLUSIONS: Repeated FIT screening (1/year for 3 years) detected all CRCs and proved equivalent to colonoscopy in detecting advanced neoplasia in first-degree relatives of patients with CRC. This strategy should be considered for populations where compliance with FITs is higher than with colonoscopy. ClinicalTrials.gov number: NCT01075633 (COLONFAM Study). PMID- 25127680 TI - Increased intake of vegetables, but not fruit, reduces risk for hepatocellular carcinoma: a meta-analysis. AB - BACKGROUND & AIMS: The anti-cancer effects of vegetables and fruit have been investigated extensively, but the association between vegetable and fruit consumption and risk of hepatocellular carcinoma (HCC) has not been quantified. We performed a meta-analysis of observational studies to clarify the association. METHODS: We identified eligible studies, published from 1956 through May 31, 2014, by searching PubMed, Web of Science, and EMBASE. Random-effects models were used to calculate summary relative risks (RRs) and dose-response analyses were conducted to quantify associations. Heterogeneity among studies was evaluated using Cochran's Q and I(2) statistics. RESULTS: A total of 19 studies involving 1,290,045 participants and 3912 cases of HCC were included in the meta-analysis. The summary RR for HCC was 0.72 for individuals with high intake vs low intake of vegetables (95% confidence interval [CI]: 0.63-0.83) and 0.92 with a daily increase in vegetable intake (100 g/d) (95% CI: 0.88-0.95). Subgroup analyses showed that this inverse association did not change regardless of history of hepatitis, alcohol drinking, smoking, or energy intake. The summary RR for HCC among individuals with high vs low intake of fruit was 0.93 (95% CI: 0.80-1.09), and 0.99 with a daily increase in fruit intake (100 g/d) (95% CI: 0.94-1.05). CONCLUSIONS: Based on a meta-analysis, increased intake of vegetables, but not fruit, is associated with lower risk for HCC. The risk of HCC decreases by 8% for every 100 g/d increase in vegetable intake. The findings should be confirmed by future studies with validated questionnaires and strict control of confounders. PMID- 25127681 TI - The effects of amphetamine, butorphanol, and their combination on cocaine self administration. AB - There have been recent calls to examine the efficacy of drug-combination therapies in the treatment of substance use disorders. The purpose of the present study was to examine the ability of a novel stimulant-opioid combination to reduce cocaine self-administration, and to compare these effects to those of each drug administered alone. To this end, male Long-Evans rats were implanted with intravenous catheters and trained to self-administer cocaine under positive reinforcement contingencies. Once self-administration was acquired, rats were divided into four different groups and treated chronically for 20 days with (1) saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and butorphanol. During chronic treatment, cocaine self-administration was examined on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. On the FR schedule, butorphanol significantly decreased cocaine self administration, but this effect was not enhanced by amphetamine. On the PR schedule, amphetamine and butorphanol non-significantly decreased cocaine self administration when administered alone but significantly decreased cocaine self administration when administered in combination. These data suggest that under some conditions (e.g., when the response requirement of cocaine is high), a dual stimulant-opioid pharmacotherapy may be more effective than a single-drug monotherapy. PMID- 25127682 TI - Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl 1,2,3,6-tetrahyropyridine. AB - A large body of evidence suggests that peroxisome proliferator-activated receptor (PPAR) agonists may improve some of the pathological features of Parkinson's disease (PD). In the present study, we evaluated the effects of the PPAR-alpha agonist fenofibrate (100mg/kg) and PPAR-gamma agonist pioglitazone (30mg/kg) in a rat model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6 tetrahyropyridine (MPTP). Male Wistar rats were pretreated with both drugs for 5 days and received an infusion of MPTP. The experiments were divided into two parts. First, 1, 7, 14, and 21 days after surgery, the animals were submitted to the open field test. On days 21 and 22, the rats were subjected to the forced swim test and two-way active avoidance task. In the second part of the study, 24h after neurotoxin administration, immunohistochemistry was performed to assess tyrosine hydroxylase activity. The levels of dopamine and its metabolites in the striatum were determined using high-performance liquid chromatography, and fluorescence detection was used to assess caspase-3 activation in the substantia nigra pars compacta (SNpc). Both fenofibrate as pioglitazone protected against hypolocomotion, depressive-like behavior, impairment of learning and memory, and dopaminergic neurodegeneration caused by MPTP, with dopaminergic neuron loss of approximately 33%. Fenofibrate and pioglitazone also protected against the increased activation of caspase-3, an effector enzyme of the apoptosis cascade that is considered one of the pathological features of PD. Thus, PPAR agonists may contribute to therapeutic strategies in PD. PMID- 25127683 TI - Mice lacking TrkB in parvalbumin-positive cells exhibit sexually dimorphic behavioral phenotypes. AB - Activity-dependent brain-derived neurotrophic factor (BDNF) signaling through receptor tyrosine kinase B (TrkB) is required for cued fear memory consolidation and extinction. Although BDNF is primarily secreted from glutamatergic neurons, TrkB is expressed by other genetically defined cells whose contributions to the behavioral effects of BDNF remain poorly understood. Parvalbumin (PV)-positive interneurons, which are highly enriched in TrkB, are emerging as key regulators of fear memory expression. We therefore hypothesized that activity-dependent BDNF signaling in PV-interneurons may modulate emotional learning. To test this hypothesis, we utilized the LoxP/Cre system for conditional deletion of TrkB in PV-positive cells to examine the impact of cell-autonomous BDNF signaling on Pavlovian fear conditioning and extinction. However, behavioral abnormalities indicative of vestibular dysfunction precluded the use of homozygous conditional knockouts in tests of higher cognitive functioning. While vestibular dysfunction was apparent in both sexes, female conditional knockouts exhibited an exacerbated phenotype, including extreme motor hyperactivity and circling behavior, compared to their male littermates. Heterozygous conditional knockouts were spared of vestibular dysfunction. While fear memory consolidation was unaffected in heterozygotes of both sexes, males exhibited impaired extinction consolidation compared to their littermate controls. Our findings complement evidence from human and rodent studies suggesting that BDNF signaling promotes consolidation of extinction and point to PV-positive neurons as a discrete population that mediates these effects in a sex-specific manner. PMID- 25127685 TI - Centrally-administered oxytocin promotes preference for familiar objects at a short delay in ovariectomized female rats. AB - Oxytocin has been previously associated with social attachment behaviors in various species, however, most studies focused on partner preference in the socially-monogamous prairie vole. In these, oxytocin treatment was shown to promote partner preference, such that females receiving either central or pulsatile peripheral administration would spend more time with a familiar male. This behavioral outcome was blocked by oxytocin receptor antagonist treatment. The aim of the current study was to further explore the preference-inducing properties of oxytocin by examining its effects on object preference on ovariectomized female rats. In other words, we assessed whether these effects would apply to objects and if they would be persistent across species. Eight rats were infused with oxytocin into the left ventricle and object preference was assessed at two delays: 30min and 4h. At the 30min delay, oxytocin-treated animals showed preference for the familiar object, whereas saline-treated controls exhibited preference for the novel object. At the 4h delay, both groups showed novel-object preference. Our findings show that oxytocin modulates object preference in the female rat at a shorter delay, similar to the findings from partner-preference studies in the prairie vole, suggesting that the mechanisms driving object preference might be in part similar to those responsible for partner preference. PMID- 25127684 TI - Tolerance to the locomotor-activating effects of 3,4 methylenedioxymethamphetamine (MDMA) predicts escalation of MDMA self administration and cue-induced reinstatement of MDMA seeking in rats. AB - Pre-clinical studies of individual differences in addiction vulnerability have been increasing over recent years, but the amphetamine derivative 3,4 methylenedioxymethamphetamine (MDMA; ecstasy) has received relatively little attention in this regard. Previously, we reported large individual differences both in rats' initial behavioral response to experimenter-administered MDMA and their degree of behavioral sensitization to repeated administration. To determine whether these differences could predict subsequent patterns of MDMA-taking or seeking behaviors we used the self-administration-extinction-reinstatement model to examine addiction-like behavior (i.e., escalation of MDMA self-administration and cue-induced reinstatement of MDMA seeking) in rats a priori characterized for either locomotor sensitization or tolerance to MDMA. Rats that developed tolerance to the locomotor-activating effects of MDMA had a significantly larger locomotor response to the first MDMA injection relative to rats that developed sensitization. Importantly, rats that developed tolerance subsequently displayed an escalation of MDMA self-administration over days, as well as clear cue-induced reinstatement of MDMA seeking following extinction. Conversely, rats that developed locomotor sensitization to MDMA subsequently maintained relatively stable levels of MDMA self-administration over days and showed no cue-induced reinstatement of MDMA seeking. These results show that differences in the level of psychomotor activation following acute and repeated MDMA administration can reliably predict two important addiction-like behaviors in rats, which may have implications in the prediction of compulsive MDMA use in humans. PMID- 25127686 TI - Rapid bio-methanation of syngas in a reverse membrane bioreactor: membrane encased microorganisms. AB - The performance of a novel reverse membrane bioreactor (RMBR) with encased microorganisms for syngas bio-methanation as well as a co-digestion process of syngas and organic substances was examined. The sachets were placed in the reactors and examined in repeated batch mode. Different temperatures and short retention time were studied. The digesting sludge encased in the PVDF membranes was able to convert syngas into methane at a retention time of 1 day and displayed a similar performance as the free cells in batch fermentation. The co digestion of syngas and organic substances by the RMBR (the encased cells) showed a good performance without any observed negative effects. At thermophilic conditions, there was a higher conversion of pure syngas and co-digestion using the encased cells compared to at mesophilic conditions. PMID- 25127687 TI - In vivo anti-hyperlipidemic activity of the triterpene from the stem bark of Protorhus longifolia (Benrh) Engl. AB - BACKGROUND: Hyperlipidemia, a metabolic disorder of lipids, is a well known risk factor of cardiovascular events and metabolic syndrome. In this study, the in vivo lipid-lowering activity of the triterpene (Methyl-3beta-hydroxylanosta-9,24 dien-21-oate), isolated from the stem bark of Protorhus longifolia, in high fat diet (HFD)-induced hyperlipidemic rats was investigated. METHODS: Structure of the isolated compound was established and confirmed based on spectral (NMR, HRMS, IR) data analysis. Rats were divided into two groups; normal group (fed the normal commercial rats' chow) and the HFD group. After 21 days of experimental period on their respective diets, the HFD rats were sub-divided into 4 groups of six rats per group. Two of the HFD groups were orally treated with the triterpene (100 and 200 mg/kg body weight) for 15 days. At the end of the experimental periods, the rats were sacrificed and blood samples were collected for biochemical assays. RESULTS: The results show that there were significant increases in total serum cholesterol (TC, 15.72 mmol/L) and low-density lipoprotein cholesterol (LDL-c, 7.41 mmol/L) with a reduction in high-density lipoprotein cholesterol (HDL-c, 14.75 mmol/L) in HFD-induced hyperlipidemic rats after 21 days. Oral administration of the triterpene (100 mg/kg.bw and 200 mg/kg.bw) for a period of 15 days resulted in significant lowering of the levels of TC (7.51 mmol/L) and LDL-c (4.46 mmol/L) with an increase in HDL-c (47.3 mmol/L) in HFD-induced hyperlipidemic rats. Significant decrease in atherogenic index and coronary risk index by the triterpene was observed in HFD-induced hyperlipidemic rats. CONCLUSIONS: The triterpene could effectively reduce or control the amount of serum cholesterol and LDL. It is apparent that the compound could contribute to new formulation with significant hypolipidemic effects. PMID- 25127688 TI - Spatial-explicit modeling of social vulnerability to malaria in East Africa. AB - BACKGROUND: Despite efforts in eradication and control, malaria remains a global challenge, particularly affecting vulnerable groups. Despite the recession in malaria cases, previously malaria free areas are increasingly confronted with epidemics as a result of changing environmental and socioeconomic conditions. Next to modeling transmission intensities and probabilities, integrated spatial methods targeting the complex interplay of factors that contribute to social vulnerability are required to effectively reduce malaria burden. We propose an integrative method for mapping relative levels of social vulnerability in a spatially explicit manner to support the identification of intervention measures. METHODS: Based on a literature review, a holistic risk and vulnerability framework has been developed to guide the assessment of social vulnerability to water-related vector-borne diseases (VBDs) in the context of changing environmental and societal conditions. Building on the framework, this paper applies spatially explicit modeling for delineating homogeneous regions of social vulnerability to malaria in eastern Africa, while taking into account expert knowledge for weighting the single vulnerability indicators. To assess the influence of the selected indicators on the final index a local sensitivity analysis is carried out. RESULTS: Results indicate that high levels of malaria vulnerability are concentrated in the highlands, where immunity within the population is currently low. Additionally, regions with a lack of access to education and health services aggravate vulnerability. Lower values can be found in regions with relatively low poverty, low population pressure, low conflict density and reduced contributions from the biological susceptibility domain. Overall, the factors characterizing vulnerability vary spatially in the region. The vulnerability index reveals a high level of robustness in regard to the final choice of input datasets, with the exception of the immunity indicator which has a marked impact on the composite vulnerability index. CONCLUSIONS: We introduce a conceptual framework for modeling risk and vulnerability to VBDs. Drawing on the framework we modeled social vulnerability to malaria in the context of global change using a spatially explicit approach. The results provide decision makers with place-specific options for targeting interventions that aim at reducing the burden of the disease amongst the different vulnerable population groups. PMID- 25127689 TI - An improved recombinant Fab-immunotoxin targeting CD22 expressing malignancies. AB - Moxetumomab pasudotox (HA22) is a recombinant immunotoxin, now in clinical trials, that combines an anti-CD22-Fv with a 38-kDa fragment of Pseudomonas exotoxin A. To produce a less immunogenic molecule without reducing the half-life in circulation, we constructed LMB11 combining an anti-CD22 Fab with a less immunogenic version of PE38. We found that LMB11 retains full activity toward CD22-expressing cells. In mice, the half-life of LMB11 is 29 min and the antitumor activity of LMB11 is better than that of HA22. Because it can be safely given at much higher doses, LMB11 produced complete tumor remissions in 7/7 mice. PMID- 25127691 TI - A generic approach to post-column refocusing in liquid chromatography. AB - To increase detection sensitivity in liquid chromatography, a generic post-column refocusing strategy has been developed to enrich (target) analytes prior to detection. In this strategy, after separation on the analytical column, the analytes are led to a trap column preferably containing a stationary phase with strong retentive properties (e.g. silica C30). They are then eluted using a strong solvent in a backward-elution mode. A first key element of the proposed strategy is that the trapping time should be at least equal to the time the front of the remobilization solvent needs to cover the entire length of the trap column, divided by the ratio of the flow rates used for trapping and remobilization. This condition is independent of the retention properties of the analytes in the trapping and remobilization solvent. Another essential element is the addition of a third solvent (isopropanol in the present case) to the remobilization solvent to overcome viscous-fingering effects caused by the viscosity difference between the trap and the remobilization solvents. The potential of the proposed post-column refocusing strategy is demonstrated for an isocratic separation of KI (t0 marker), an antibiotic (sulfamethazine), and acetophenone as a case study. Using optimized remobilization conditions a maximum signal-enhancement factor of 8 was achieved. Higher enhancement factors using a remobilization solvent with slightly higher elution strength were prohibited by disturbances of the UV background signal. PMID- 25127690 TI - The prognostic importance of polypharmacy in older adults treated for acute myelogenous leukemia (AML). AB - We retrospectively evaluated the prognostic significance of polypharmacy and inappropriate medication use among 150 patients >60 years of age receiving induction chemotherapy for acute myelogenous leukemia (AML). After adjustment for age and comorbidity, increased number of medications at diagnosis (>= 4 versus <= 1) was associated with increased 30-day mortality (OR=9.98, 95% CI=1.18-84.13), lower odds of complete remission status (OR=0.20, 95% CI=0.06-0.65), and higher overall mortality (HR=2.13, 95% CI=1.15-3.92). Inappropriate medication use (classified according to Beers criteria) was not significantly associated with clinical outcomes. Polypharmacy warrants further study as a modifiable marker of vulnerability among older adults with AML. PMID- 25127692 TI - Optimization of reactive simulated moving bed systems with modulation of feed concentration for production of glycol ether ester. AB - In this article, we extend the simulated moving bed reactor (SMBR) mode of operation to the production of propylene glycol methyl ether acetate (DOWANOLTM PMA glycol ether) through the esterification of 1-methoxy-2-propanol (DOWANOLTM PM glycol ether) and acetic acid using AMBERLYSTTM 15 as a catalyst and adsorbent. In addition, for the first time, we integrate the concept of modulation of the feed concentration (ModiCon) to SMBR operation. The performance of the conventional (constant feed) and ModiCon operation modes of SMBR are analyzed and compared. The SMBR processes are designed using a model based on a multi-objective optimization approach, where a transport dispersive model with a linear driving force for the adsorption rate has been used for modeling the SMBR system. The adsorption equilibrium and kinetics parameters are estimated from the batch and single column injection experiments by the inverse method. The multiple objectives are to maximize the production rate of DOWANOLTM PMA glycol ether, maximize the conversion of the esterification reaction and minimize the consumption of DOWANOLTM PM glycol ether which also acts as the desorbent in the chromatographic separation. It is shown that ModiCon achieves a higher productivity by 12-36% over the conventional operation with higher product purity and recovery. PMID- 25127693 TI - A let-7 microRNA polymorphism in the KRAS 3'-UTR is prognostic in oropharyngeal cancer. AB - INTRODUCTION: This study aimed to investigate the effect of genetic polymorphisms in miRNA sequences, miRNA target genes and miRNA processing genes as additional biomarkers to HPV for prognosis in oropharyngeal squamous cell carcinoma (OPSCC) patients. Secondarily, the prevalence of HPV-associated OPSCC in a European cohort was mapped. METHODS: OPSCC patients (n=122) were genotyped for ten genetic polymorphisms in pre-miRNAs (pre-mir-146a, pre-mir-196a2), in miRNA biosynthesis genes (Drosha, XPO5) and in miRNA target genes (KRAS, SMC1B). HPV status was assessed by p16 immunohistochemistry (IHC) and high-risk HPV in situ hybridization (ISH) or by p16 IHC and PCR followed by enzyme-immunoassay (EIA). Overall and disease specific survival were analysed using Kaplan-Meier plots (log rank test). Cox proportional hazard model was used to calculate hazard ratios (HR). RESULTS: The overall HPV prevalence rate in our Belgian/Dutch cohort was 27.9%. Patients with HPV(+) tumours had a better 5-years overall survival (78% vs. 46%, p=0.001) and a better 5-years disease specific survival (90% vs. 70%, p=0.016) compared to patients with HPV(-) tumours. In multivariate Cox analysis including clinical, treatment and genetic parameters, HPV negativity (HR=3.89, p=0.005), advanced T-stage (HR=1.81, p=0.050), advanced N-stage (HR=5.86, p=0.001) and >10 pack-years of smoking (HR=3.45, p=0.012) were significantly associated with reduced overall survival. The variant G-allele of the KRAS-LCS6 polymorphism was significantly associated with a better overall survival (HR=0.40, p=0.031). CONCLUSIONS: Our results demonstrate that OPSCC patients with the KRAS-LCS6 variant have a better outcome and suggest that this variant may be used as a prognostic biomarker for OPSCC. PMID- 25127694 TI - Aniseikonia following pneumatic retinopexy for rhegmatogenous retinal detachment. AB - PURPOSE: To evaluate the characteristics of aniseikonia in patients with rhegmatogenous retinal detachment (RD) after pneumatic retinopexy. DESIGN: Prospective, interventional case series study. METHODS: Thirty patients who had undergone pneumatic retinopexy as the initial procedure for rhegmatogenous retinal detachment were selected for this study. The principal outcomes included visual acuity, postoperative aniseikonia measured by the New Aniseikonia Test, anatomical success, and measurement of central retinal thickness using optical coherence topography (OCT). These outcomes were measured postoperatively at 3, 6, and 12 months. RESULTS: The median patient age was 37 years (range, 13-57 years), with 17 cases of macula-off RD and 13 cases of macula-on RD. All of these patients achieved anatomical success, proven by OCT after surgical repair. Three months after pneumatic retinopexy, 18 patients (60.0%) developed micropsic aniseikonia and aniseikonia was diagnosed in 15 patients (88.2%) in the macula off RD group, leaving 2 patients (11.8%) unaffected. In the macula-on RD group, 3 patients (23.1%) were found to have aniseikonia, while 10 patients (76.9%) were unaffected. The presence of aniseikonia was strongly linked to the difference in central retinal thickness, between the operated eye and the fellow eye, measured at 12 months postoperatively. CONCLUSION: Aniseikonia after pneumatic retinopexy for rhegmatogenous RD may be related to the preoperative macular status. Macula off RD patients had a higher incidence of aniseikonia, compared to macula-on RD patients, following retina reattachment. There was a moderate to high correlation between the grading of aniseikonia and the difference in central retinal thickness. PMID- 25127695 TI - Clinicopathological findings in abusive head trauma: analysis of 110 infant autopsy eyes. AB - PURPOSE: To investigate the histopathology in a large series of autopsy eyes from children with abusive head trauma. DESIGN: Retrospective case-control series. METHODS: One hundred and ten eyes from 55 autopsies examined at an academic tertiary referral center over 21 years were tabulated for histopathology: subdural hemorrhage in the optic nerve sheath, intrascleral hemorrhage, any retinal hemorrhage, ora-extended hemorrhage, cherry hemorrhage, perimacular ridge, and internal limiting membrane tear. Select tissues with cherry hemorrhage were further examined by transmission electron microscopy. RESULTS: Sixty eyes were identified as "abusive head trauma" (cases), 46 as "alternative cause" (controls), and 4 as "abusive head trauma survivor". Cases were legally verified or confirmed by confession in all except 1 case. All ocular histopathologic observations from cases were similar or more frequent in infants younger than 16 months of age. When present, a cherry hemorrhage and perimacular ridge were most often found together, and only with a torn internal limiting membrane. Both abusive head trauma survivor cases demonstrated severe optic nerve atrophy and macular ganglion cell loss. CONCLUSIONS: Younger infants may be even more susceptible to damage from vitreomacular traction by rotational and/or acceleration-deceleration forces. Identifying cherry hemorrhages may aid abusive head trauma diagnosis. Survivor abusive head trauma pathology demonstrates unique, irreversible macular and optic nerve damage. PMID- 25127696 TI - The subject-fixated coaxially sighted corneal light reflex: a clinical marker for centration of refractive treatments and devices. AB - PURPOSE: To describe the inconsistencies in definition, application, and usage of the ocular reference axes (optical axis, visual axis, line of sight, pupillary axis, and topographic axis) and angles (angle kappa, lambda, and alpha) and to propose a precise, reproducible, clinically defined reference marker and axis for centration of refractive treatments and devices. DESIGN: Perspective. METHODS: Literature review of papers dealing with ocular reference axes, angles, and centration. RESULTS: The inconsistent definitions and usage of the current ocular axes, as derived from eye models, limit their clinical utility. With a clear understanding of Purkinje images and a defined alignment of the observer, light source/fixation target, and subject eye, the subject-fixated coaxially sighted corneal light reflex can be a clinically useful reference marker. The axis formed by connecting the subject-fixated coaxially sighted corneal light reflex and the fixation point, the subject-fixated coaxially sighted corneal light reflex axis, is independent of pupillary dilation and phakic status of the eye. The relationship of the subject-fixated coaxially sighted corneal light reflex axis to a refined definition of the visual axis without reference to nodal points, the foveal-fixation axis, is discussed. The displacement between the subject-fixated coaxially sighted corneal light reflex and pupil center is described not by an angle, but by a chord, here termed chord mu. The application of the subject fixated coaxially sighted corneal light reflex to the surgical centration of refractive treatments and devices is discussed. CONCLUSION: As a clinically defined reference marker, the subject-fixated coaxially sighted corneal light reflex avoids the shortcomings of current ocular axes for clinical application and may contribute to better consensus in the literature and improved patient outcomes. PMID- 25127698 TI - Punctate hyperfluorescence spot as a common choroidopathy of central serous chorioretinopathy and polypoidal choroidal vasculopathy. AB - PURPOSE: To characterize punctate hyperfluorescence spot as common choroidopathy in central serous chorioretinopathy (CSC) and polypoidal choroidal vasculopathy (PCV). DESIGN: Cross-sectional retrospective study. METHODS: A total of 150 patients with 50 each allocated to CSC, PCV, and typical neovascular age-related macular degeneration (AMD) groups were included. Punctate hyperfluorescence spot was determined using mid-to late-phase indocyanine green angiography and subfoveal choroidal thickness by enhanced depth imaging optical coherence tomography. Each group was subcategorized based on concurrent punctate hyperfluorescence spot. RESULTS: The punctate hyperfluorescence spot incidence was higher in CSC (80.0%) and PCV (86.0%) than in AMD (40.0%, P < .001), with similar contralateral findings (86.1%, 86.7%, and 60%, respectively, P = .014). Punctate hyperfluorescence spot lesions comprised clustered polyps connected to vascular networks mimicking PCV. Choroidal thickness was 370.7 +/- 81.9 MUm, 332.6 +/- 101.6 MUm, and 172.5 +/- 80.1 MUm in affected eyes (P < .001) and 323.0 +/- 70.5 MUm, 306.4 +/- 94.4 MUm, and 180.2 +/- 83.6 MUm in contralateral eyes (P < .001) in CSC, PCV, and AMD groups, respectively. In the AMD group, choroidal thickness was greater in eyes with punctate hyperfluorescence spot (204.8 +/- 92.3 MUm) than in those without punctate hyperfluorescence spot (150.2 +/- 62.9 MUm, P = .028) in affected eyes; however, the difference was not observed in contralateral eyes in the AMD group and in both eyes in the CSC and PCV groups. CONCLUSIONS: Based on angiography and OCT, punctate hyperfluorescence spot may be a form of PCV, and CSC and PCV may share common choroidopathy distinct from typical neovascular AMD. However, infrequent PHS lesions along with thickened choroids in AMD eyes suggest that AMD may encompass a wide choroidal pathologic spectrum shared in part with PCV. PMID- 25127697 TI - Three-dimensional automated choroidal volume assessment on standard spectral domain optical coherence tomography and correlation with the level of diabetic macular edema. AB - PURPOSE: To measure choroidal thickness on spectral-domain optical coherence tomography (SD OCT) images using automated algorithms and to correlate choroidal pathology with retinal changes attributable to diabetic macular edema (DME). DESIGN: Post hoc analysis of multicenter clinical trial baseline data. METHODS: SD OCT raster scans/fluorescein angiograms were obtained from 284 treatment-naive eyes of 142 patients with clinically significant DME and from 20 controls. Three dimensional (3D) SD OCT images were evaluated by a certified independent reading center analyzing retinal changes associated with diabetic retinopathy. Choroidal thicknesses were analyzed using a fully automated algorithm. Angiograms were assessed manually. Multiple endpoint correction according to Bonferroni-Holm was applied. Main outcome measures were average retinal/choroidal thickness on fovea centered or peak of edema (thickest point of edema)-centered Early Treatment Diabetic Retinopathy Study grid, maximum area of leakage, and the correlation between retinal and choroidal thicknesses. RESULTS: Total choroidal thickness is significantly reduced in DME (175 +/- 23 MUm; P = .0016) and nonedematous fellow eyes (177 +/- 20 MUm; P = .009) of patients compared with healthy control eyes (190 +/- 23 MUm). Retinal/choroidal thickness values showed no significant correlation (1-mm: P = .27, r(2) = 0.01; 3-mm: P = .96, r(2) < 0.0001; 6-mm: P = .42, r(2) = 0.006). No significant difference was found in the 1- or 3-mm circle of a retinal peak of edema-centered grid. All other measurements of choroidal/retinal thickness (DME vs healthy, DME vs peak of edema-centered, DME vs fellow, healthy vs fellow, peak of edema-centered vs healthy, peak of edema centered vs fellow eyes) were compared but no statistically significant correlation was found. By tendency a thinner choroid correlates with larger retinal leakage areas. CONCLUSIONS: Automated algorithms can be used to reliably assess choroidal thickness in eyes with DME. Choroidal thickness was generally reduced in patients with diabetes if DME is present in 1 eye; however, no correlation was found between choroidal/retinal pathologies, suggesting different pathogenetic pathways. PMID- 25127699 TI - Scleral-fixated capsular tension rings and segments for ectopia lentis in children. AB - PURPOSE: To report the short-term outcomes and complications of implantation of scleral-fixated capsular tension rings and/or capsular tension segments with intraocular lenses (IOL) in pediatric patients with ectopia lentis. DESIGN: Retrospective, observational case series. METHODS: Thirteen consecutive pediatric patients (19 eyes) underwent placement of in-the-bag IOL with either a Cionni modified capsular tension ring or a capsular tension segment in conjunction with a conventional capsular tension ring between January 1, 2009 and March 30, 2013 by 3 anterior segment surgeons at a single academic center. The scleral fixation suture was 9-0 polypropylene in 16 eyes and CV-8 Gore-Tex (expanded polytetrafluoroethylene) in 3 eyes. Outcome measures included change in corrected distance visual acuity (CDVA) and complications. RESULTS: The mean age was 10.2 years +/- 4.8 (SD) and the median follow-up, 23.4 months. A Cionni modified capsular tension ring was implanted in 5 eyes and a capsular tension segment with an unsutured capsular tension ring was implanted in 12 eyes. In 2 eyes, capsular tension segment alone was placed. The mean CDVA at the final follow-up (0.10 +/- 0.11 logMAR, 18 eyes) was significantly better than preoperatively (0.58 +/- 0.26 logMAR, 15 eyes) (P < .001). The CDVA at the final follow-up was 20/40 or better in 18 eyes (94.7%). All IOLs were well centered. Posterior capsule opacification developed in 11 eyes (57.9%), 9 eyes (47.4%) required neodymium-yttrium-aluminum garnet capsulotomy, and 3 eyes (15.8%) required pars plana vitrectomy and posterior capsulotomy. Other complications included broken suture (5.3%) (9-0 polypropylene at CTR eyelet, repaired with CV-8 Gore-Tex), conjunctival dehiscence (5.3%), suture exposure (5.3%) (trans-scleral 9-0 polypropylene), and vitreous strand at inferior paracentesis (5.3%). CONCLUSIONS: Implantation of in the-bag IOL with either a Cionni modified capsular tension ring or a capsular tension segment in conjunction with a conventional capsular tension ring appears to be a safe and effective technique for visual rehabilitation in pediatric ectopia lentis. PMID- 25127700 TI - Anterior segment optical coherence tomography measurement after neodymium-yttrium aluminum-garnet laser capsulotomy. AB - PURPOSE: To evaluate changes in anterior chamber depth (ACD) and angle width after neodymium-yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy. DESIGN: Prospective interventional case series. METHODS: In a single institution, 43 eyes of 43 consecutive pseudophakic patients with symptomatic posterior capsule opacification (PCO) underwent Nd:YAG laser capsulotomy. Anterior chamber depth and angle width in pseudophakic eyes with posterior capsule opacification were measured with anterior segment optical coherence tomography (AS-OCT) before and 3 days after Nd:YAG laser capsulotomy. Preoperative and postoperative measurements of anterior chamber depth and angle width included the angle opening distance, measured as the perpendicular distance from the trabecular meshwork at 500 MUm and 750 MUm anterior to the scleral spur to the anterior iris surface (AOD500 and AOD750, respectively), and anterior chamber angle (ACA) in the nasal and temporal quadrants. Main outcome measures were the changes in ACD and angle width parameters. RESULTS: The mean patient age was 63.4 +/- 3.6 years. Before Nd:YAG laser capsulotomy, mean ACD, AOD500, AOD750, and ACA (nasal and temporal) measurements were 3.71 +/- 0.11 mm, 0.61 +/- 0.054 mm, 0.67 +/- 0.063 mm, and 34.5 +/- 1.67 degrees and 34.8 +/- 1.55 degrees, respectively. Three days after Nd:YAG laser capsulotomy, mean ACD, AOD500, AOD750, and ACA (nasal and temporal) measurements were 3.77 +/- 0.1 mm, 0.69 +/- 0.06 mm, 0.73 +/- 0.06 mm, and 35.51 +/- 1.64 degrees and 36.17 +/- 1.51 degrees, respectively (P < .01 for all). CONCLUSIONS: The depth and width of the ACA in pseudophakic eyes with PCO increased significantly after Nd:YAG laser capsulotomy, as shown by AS-OCT, a reliable and noncontact method for measuring anterior ocular structures. Our study shows that the different angle parameters such as ACD, AOD500, AOD750, and ACA measurements seem highly correlated. PMID- 25127701 TI - Surgical outcomes of progressive tractional retinal detachment associated with familial exudative vitreoretinopathy. AB - PURPOSE: To evaluate various surgeries for treating retinal detachment (RD) associated with familial exudative vitreoretinopathy (FEVR). DESIGN: Retrospective, interventional case series. METHODS: The charts of 22 patients who underwent surgery were reviewed. A complete ophthalmic examination was performed including wide-field fundus images with fluorescein angiography. The primary and secondary outcomes were fundus features (vascular activity of the fibrovascular proliferation and extent of tractional RD) and visual acuity (VA), respectively. RESULTS: Thirty-one eyes were included (12 eyes underwent scleral buckling, 1 scleral buckling and vitrectomy, 7 vitrectomy alone, and 11 lensectomy and vitrectomy). Twenty-six eyes were reattached during 1 surgery. Scleral buckling resulted in cessation of fibrovascular proliferation and retinal reattachment; only 1 of these eyes required vitrectomy. Lens-sparing vitrectomy resulted in stabilized fibrovascular proliferation and retinal reattachment. Vitrectomy with lensectomy did not achieve retinal reattachment in 4 eyes. Fibrovascular proliferation has a rich vascular component in patients younger than 3 years, and collagen fibers were present mainly with more advanced age. The postoperative VA improved in 5 of 8 eyes examined, was unchanged in 1 eye, and decreased in 2 eyes with macular involvement. CONCLUSIONS: FEVR-induced RDs are highly variable and require careful preoperative evaluation to determine the best surgical procedure. Vitrectomy with release of posterior traction is essential in younger patients with vascularly active fibrovascular proliferation, whereas scleral buckling may be important for cases with peripheral traction anterior to the equator. In all cases, peripheral thermal treatment applied to all ischemic areas contributed to reduced peripheral neovascularization. PMID- 25127702 TI - [Evaluation of visual performance after implantation of a double C-Loop toric intraocular lens]. AB - PURPOSE: This study aims to demonstrate the safety and the efficacy of the Ankoris posterior chamber intraocular lens to correct corneal astigmatism at the time of cataract surgery. MATERIAL AND METHODS: In this retrospective study, 52 eyes among the first 64 consecutive ones implanted with the Ankoris met the inclusion criteria. The retrospective analysis of these cases consisted mainly of the determination of the improvement in visual acuity and postoperative refraction. The analysis of the astigmatism correction itself was carried out by the Alpins method. The rotational stability of the implant was analyzed by the difference between the IOL orientation after one day and 3 months. RESULTS: The safety index, defined as the postoperative divided by preoperative best visual acuity, was greater than one in all cases, with a mean of 1.96. The ratio of the postoperative uncorrected visual acuity with the preoperative best-corrected acuity was 1.72. The final postoperative astigmatism was -0.40 +/- 0.28 D. The percentage of astigmatism corrected was 99.3%. The error vector amplitude was 0.1 D with a nearly null orientation. The mean rotation was 2.16 +/- 1.95 degrees . CONCLUSION: The Ankoris IOL demonstrates, in this relatively large cohort, all necessary elements to establish that the IOL was able to correct corneal astigmatism at the same time as cataract surgery. PMID- 25127703 TI - Ocular tolerability and efficacy of a cationic emulsion in patients with mild to moderate dry eye disease - a randomised comparative study. AB - PURPOSE: The purpose of this study was to compare the safety and efficacy of a new cationic emulsion (CE) with a formulation of polyvinyl alcohol and povidone (PVA-P) for the treatment of mild to moderate dry eye disease. METHODS: This was a multicenter, open-label, comparative study. Patients were randomised to receive CE (Cationorm) or PVA-P (Refresh) (1:1). The following objective criteria were assessed to compare the two eye drops: tear Break-up Time (TBUT), Schirmer's test, lissamine green staining (Van Bijsterveld score), corneal fluorescein staining (Oxford scale) and oculopalpebral examination, on D7 and D28 (end of study). At these visits, ocular symptoms and safety were also assessed. RESULTS: Seventy-nine patients were randomised: CE: 44 patients; PVA-P: 35 patients. At D28, improvement was significantly better for TBUT [CE: 1.7 +/- 2.4 s; PVA-P: 0.6 +/- 1.8 s; P=0.015] and for the Van Bijsterveld score [CE: -1.4 +/- 1.2; PVA-P: 0.9 +/- 1.2; P=0.046] in the CE group. The same applied for the palpebral erythema score (P=0.023), overall efficacy assessed by the investigators (P<0.001), and symptoms not related to eye drop instillation (P=0.021). Improvement was observed from D7. No difference was observed between the two treatments with regard to ocular safety. CONCLUSION: These results suggest that in patients with mild to moderate dry eye, Cationorm, in addition to its moisturizing and lubricating properties, also helps stabilize the tear film due to its oily component. This study demonstrates the benefit of this new pharmaceutical form for the treatment of mild to moderate dry eye disease. PMID- 25127704 TI - Abstinence phenomena of chronic cannabis-addicts prospectively monitored during controlled inpatient detoxification: cannabis withdrawal syndrome and its correlation with delta-9-tetrahydrocannabinol and -metabolites in serum. AB - OBJECTIVE: To investigate the course of cannabis withdrawal syndrome (CWS) within a controlled inpatient detoxification setting and to correlate severity of CWS with the serum-levels of delta-9-tetrahydrocannabinol (THC) and its main metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-delta-9 tetrahydrocannabinol-9-carboxylic acid (THC-COOH). METHODS: Thirty-nine treatment seeking chronic cannabis dependents (ICD-10) were studied on admission and on abstinent days 2, 4, 8 and 16, using a CWS-checklist (MWC) and the Clinical Global Impression-Severity scale (CGI-S). Simultaneously obtained serum was analysed to its concentration of THC, THC-OH and THC-COOH. RESULTS: MWC peaked on day 4 (10.4 +/- 4.6 from 39 points) and declined to 2.9 +/- 2.4 points on day 16. Women had a significantly stronger CWS than men. The CWS was dominated by craving>restlessness>nervousness>sleeplessness. CGI-S peaked with 5 out of 7 points. On admission, THC and its metabolites did negatively correlate with the severity of CWS. There was no significant correlation afterwards, no matter if CWS was medicated or not. THC-OH in serum declined most rapidly below detection limit, on median at day 4. At abstinence day 16, the THC-levels of 28.2% of the patients were still above 1g/ml (range: 1.3 to 6.4 ng/ml). CONCLUSIONS: CWS increased and then decreased without any correlation between its severity and the serum-levels of THC or its main metabolites after admission. According to the CGI S, most patients achieved the condition of 'markedly ill'. Serum THC-OH was most clearly associated with recent cannabis use. Residual THC was found in the serum of almost one-third of the patients at abstinence day 16. PMID- 25127706 TI - Early epileptiform discharges and the yield of prolonged EEG monitoring. PMID- 25127705 TI - Interactions among drinking identity, gender and decisional balance in predicting alcohol use and problems among college students. AB - BACKGROUND: The aim of the present study was to test promising constructs (decisional balance and drinking identity) and their interaction with gender as predictors of risky college drinking. We expected that, consistent with previous work, drinking identity would be positively associated with alcohol consumption and problems. We further expected that drinking identity would be more strongly related to outcomes among individuals scoring low in decisional balance. Additionally, we expect the relationship between drinking identity and alcohol behavior to vary as a function of decisional balance. METHODS: Participants included 329 undergraduates (M=23.11; SD=5.63; 74.47% female) who met heavy drinking criteria (defined as women who consumed 4 or more drinks per occasion and men who consumed 5 or more drinks per occasion) and completed an online survey comprised of self-report measures. RESULTS: Decisional balance was negatively correlated with both drinking and problems, which partially supported expectations. As expected, drinking identity was positively correlated with drinking and problems. A two-way interaction emerged between drinking identity and decisional balance regarding problems, indicating that drinking identity was associated with more problems, especially among those lower in decisional balance. A three-way interaction between drinking identity, decisional balance, and gender emerged regarding problems such that drinking identity was associated with more problems for those lower in decisional balance and this effect was stronger among men. DISCUSSION: Findings lend support to the perspective that decisional balance, drinking identity, and gender are all influential factors that are associated with the experience of alcohol problems. PMID- 25127707 TI - Multiscale Lempel-Ziv complexity for EEG measures. AB - OBJECTIVE: To demonstrate that the classical calculation of Lempel-Ziv complexity (LZC) has an important limitation when applied to EEGs with rapid rhythms, and to propose a multiscale approach that overcomes this limitation. METHODS: We have evaluated, both with simulated and real EEGs, whether LZC calculation neglects functional characteristics of rapid EEG rhythms. In addition, we have proposed a procedure to obtain multiple binarization sequences that yield a spectrum of LZC, and we have explored whether complexity would be better captured using this computation. RESULTS: In our simulated signals, classical LZC did not capture modulations of a rapid component when a slower component of more amplitude was included in the signal. In real EEGs from healthy participants with eyes closed and eyes open, classical LZC calculation failed to show any difference between these two conditions. However, a multiscale LZC showed that complexity was lower for eyes closed than for eyes open conditions. CONCLUSIONS: As hypothesized, our new approximation captures the complexity of series with fast components masked by slower rhythms. SIGNIFICANCE: The method we introduce significantly improves LZC calculation, and it allows a better characterization of complexity of EEG signals. PMID- 25127708 TI - Variation in charges for 10 common blood tests in California hospitals: a cross sectional analysis. AB - OBJECTIVES: To determine the variation in charges for 10 common blood tests across California hospitals in 2011, and to analyse the hospital and market-level factors that may explain any observed variation. DESIGN, SETTING AND PARTICIPANTS: We conducted a cross-sectional analysis of the degree of charge variation between hospitals for 10 common blood tests using charge data reported by all non-federal California hospitals to the California Office of Statewide Health Planning and Development in 2011. OUTCOME MEASURES: Charges for 10 common blood tests at California hospitals during 2011. RESULTS: We found that charges for blood tests varied significantly between California hospitals. For example, charges for a lipid panel ranged from US$10 to US$10,169, a thousand-fold difference. Although government hospitals and teaching hospitals were found to charge significantly less than their counterparts for many blood tests, few other hospital characteristics and no market-level predictors significantly predicted charges for blood tests. Our models explained, at most, 21% of the variation between hospitals in charges for the blood test in question. CONCLUSIONS: These findings demonstrate the seemingly arbitrary nature of the charge setting process, making it difficult for patients to act as true consumers in this era of 'consumer-directed healthcare.' PMID- 25127709 TI - Synergistic loss of prostate cancer cell viability by coinhibition of HDAC and PARP. AB - Tumors with BRCA germline mutations are defective in repairing DNA double-strand breaks (DSB) through homologous recombination (HR) pathways, making them sensitive to PARP inhibitors (PARPi). However, BRCA germline mutations are rare in prostate cancer limiting the ability to therapeutically target these pathways. This study investigates whether histone deacetylase (HDAC) inhibitors (HDACi), reported to modulate DSB repair pathways in sporadic cancers, can downregulate DSB repair pathways and sensitize prostate cancer cells to PARPi. Prostate cancer cells cotreated with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) and the PARPi, olaparib, demonstrated a synergistic decrease in cell viability compared with single-agent treatment (combination index < 0.9), whereas normal prostatic cells did not. Similarly, clonogenicity was significantly decreased after cotreatment. Flow cytometric cell-cycle analysis and Annexin-V staining revealed significant apoptosis upon treatment with SAHA+olaparib. This coincided with increased DNA damage observed by immunofluorescence microscopy analysis of gammaH2AX foci, a marker of DSBs. In addition, immunoblot analysis showed a significant and persistent increase in nuclear gammaH2AX levels. Both SAHA and olaparib downregulated the expression of HR-related proteins, BRCA1 and RAD51, whereas SAHA + olaparib had an additive effect on RAD51. Silencing RAD51 sensitized prostate cancer cells to SAHA and olaparib alone. Collectively, cotreatment with HDACi and PARPi downregulated HR-related protein expression and concomitantly increased DNA damage, resulting in prostate cancer cell death. IMPLICATIONS: These findings provide a strong rationale for supporting the use of combined HDAC and PARP inhibition in treating advanced prostate cancer. PMID- 25127711 TI - EJE Prize 2012: Obesity: from genes to behaviour. AB - An increase in the consumption of highly palatable foods coupled with a reduction in the amount of voluntary exercise undertaken has contributed to the rising prevalence of obesity. However, despite the obvious environmental influences, there is considerable evidence to support a genetic component to weight gain. In some people, particularly those who are severely obese, genetic factors play a major role in the development of their obesity and associated complications. Studies into the genetic basis of obesity have yielded insights into the mechanisms involved in the regulation of weight. We now understand that weight is regulated by neural mechanisms that regulate appetite and energy expenditure and that disruption of these pathways can result in severe obesity in some patients. These studies provide a starting point for investigating patients with severe obesity and may ultimately guide the development of more rational targeted therapies. PMID- 25127710 TI - Polymorphisms in the haemagglutinin gene influenced the viral shedding of pandemic 2009 influenza virus in swine. AB - Interactions between the viral surface glycoprotein haemagglutinin (HA) and the corresponding receptors on host cells is one important aspect of influenza virus infection. Mutations in HA have been described to affect pathogenicity, antigenicity and the transmission of influenza viruses. Here, we detected polymorphisms present in HA genes of two pandemic 2009 H1N1 (H1N1pdm09) isolates, A/California/04/2009 (Ca/09) and A/Mexico/4108/2009 (Mx/09), that resulted in amino acid changes at positions 186 (S to P) and 194 (L to I) of the mature HA1 protein. Although not reported in the published H1N1pdm09 consensus sequence, the P186 genotype was more readily detected in primary infected and contact-naive pigs when inoculated with a heterogeneous mixed stock of Ca/09. Using reverse genetics, we engineered Ca/09 and Mx/09 genomes by introducing Ca/09 HA with two naturally occurring variants expressing S186/I194 (HA-S/I) and P186/L194 (HA P/L), respectively. The Ca/09 HA with the combination of P186/L194 with either the Ca/09 or Mx/09 backbone resulted in higher and prolonged viral shedding in naive pigs. This efficiency appeared to be more likely through an advantage in cell surface attachment rather than replication efficiency. Although these mutations occurred within the receptor-binding pocket and the Sb antigenic site, they did not affect serological cross-reactivity. Relative increases of P186 in publicly available sequences from swine H1N1pdm09 viruses supported the experimental data, indicating this amino acid substitution conferred an advantage in swine. PMID- 25127712 TI - The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients. AB - OBJECTIVE: Quality of life (QoL) is impaired in hypopituitary patients and patients with primary adrenal insufficiency. The aim of this study was to analyse the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was that ACTH-insufficient patients experience a dose-dependent deterioration in QoL. DESIGN, PATIENTS AND METHODS: This was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Data from 2737 adult GH-deficient (GHD) hypopituitary patients were eligible for analysis. Thirty-six per cent were ACTH sufficient and 64% ACTH insufficient receiving a mean+/-s.d. hydrocortisone equivalent (HCeq) dose of 22.3+/-8.7 mg (median 20.0). QoL at baseline and 1 year after commencement of GH replacement was assessed by the QoL-assessment of GHD in adults. RESULTS: At baseline, no significant difference in QoL was observed between ACTH-sufficient and -insufficient patients. Increasing HCeq dose was associated with worse QoL. Patients on HCeq<=10 mg had the best and patients receiving >=25 mg demonstrated the poorest QoL. At 1 year of GH replacement, the improvement in QoL did not differ between ACTH-sufficient and -insufficient patients, and no association was observed between HCeq dose and QoL improvement. CONCLUSION: Adult hypopituitary patients with untreated GHD receiving GC replacement have similar QoL as ACTH-sufficient patients. Among ACTH-insufficient patients, there is a dose-dependent association between increasing dose and impaired QoL. This association may be explained by supraphysiological GC exposure although it remains plausible that clinicians may have increased GC doses in order to address otherwise unexplained QoL deficits. PMID- 25127713 TI - Human epididymis protein 4 (HE4) in laboratory medicine and an algorithm in renal disorders. AB - Over the past three decades, cancer antigen (CA) 125 has been utilized for monitoring women who were treated for ovarian cancer. However, this tumor marker showed several limitations such as false elevation in benign pelvic diseases and, in turn, no alterations in ovarian tumors at early stages with a relatively high ratio. For more than ten years, the human epididymis protein 4 (HE4) has become available for the routine laboratory repertoire, showing a higher sensitivity and specificity compared to that of CA125 in ovarian malignancies, but also in other types of tumors based on recently accumulated clinical data. Despite its remarkable diagnostic characteristics, in certain cases, the evaluation of HE4 results may be problematic when patients suffer from additional conditions that may alter HE4 level. Besides the direct effects of age and smoking, menopause status and decreased renal function also show a substantial impact on HE4 values, which should be considered in each patient. For this purpose, we attempted to create a new formula and an algorithm that may be helpful to predict the probability of the presence of ovarian tumor by using the concentrations of HE4 and CA125. PMID- 25127714 TI - A qualitative synthesis of diabetes self-management strategies for long term medical outcomes and quality of life in the UK. AB - BACKGROUND: Qualitative research on self-management for people with Type 2 Diabetes Mellitus (T2DM) has typically reported one-off retrospective accounts of individuals' strategies. The aim of this research was to identify the ways in which self-management strategies are perceived by people with T2DM as being either supportive or unsupportive over time, by using qualitative findings from both longitudinal intervention studies and usual care. METHODS: A systematic review of qualitative literature, published between 2000 and 2013, was conducted using a range of searching techniques. 1374 prospective qualitative papers describing patients' experiences of self-management strategies for T2DM were identified and screened. Of the 98 papers describing qualitative research conducted in the UK, we identified 4 longitudinal studies (3 intervention studies, 1 study of usual care). Key concepts and themes were extracted, reviewed and synthesised using meta-ethnography techniques. RESULTS: Aspects of self management strategies in clinical trials (e.g. supported exercise regimens) can be perceived as enabling the control of biomarkers and facilitative of quality of life. In contrast, aspects of self-management strategies outwith trial conditions (e.g. self-monitoring) can be perceived of as negative influences on quality of life. For self-management strategies to be sustainable in the long term, patients require a sense of having a stake in their management that is appropriate for their beliefs and perceptions, timely information and support, and an overall sense of empowerment in managing their diabetes in relation to other aspects of their life. This enables participants to develop flexible diabetes management strategies that facilitate quality of life and long term medical outcomes. CONCLUSIONS: This synthesis has explored how patients give meaning to the experiences of interventions for T2DM and subsequent attempts to balance biomarkers with quality of life in the long term. People with T2DM both construct and draw upon causal accounts as a resource, and a means to counter their inability to balance medical outcomes and quality of life. These accounts can be mediated by the provision of timely and tailored information and support over time, which can allow people to develop a flexible regimen that can facilitate both quality of life and medical outcomes. PMID- 25127715 TI - Comparison of single and two-tunnel techniques during open treatment of acromioclavicular joint disruption. AB - BACKGROUND: Coracoclavicular (CC) ligament reconstruction with semitendinosus tendon (ST) grafts has become more popular and has achieved relatively good results; however optimal reconstruction technique, single-tunnel or two-tunnel, still remains controversial. This paper is to compare the clinical and radiographic data of allogenous ST grafting with single- or two-tunnel reconstruction techniques of the AC joint. METHODS: The outcomes of 21 consecutive patients who underwent anatomical reduction and ST grafting for AC joint separation were reviewed retrospectively. Patients were divided into two groups: single-tunnel group (11) and two-tunnel group (10). All patients were evaluated clinically and radiographically using a modified UCLA rating scale. RESULTS: The majority of separations (18 of 21) were Rockwood type V, with one each in type III, IV and VI categories. The overall mean follow-up time was 16 months, and at the time of the latest follow-up, the overall mean UCLA rating score was 14.1 (range 8-20).The percentage of good-to-excellent outcomes was significantly higher for patients with the two-tunnel technique than for those with the one-tunnel technique (70% vs. 18%, respectively, p = 0.03). Within the single-tunnel group, there was no statistically significant difference in percentage of good-to-excellent outcomes between patients with vs. without tightrope augmentation (17% vs 20%, p > 0.99). Similarly, within the two-tunnel group, there was no significant difference in the percentage of good-to-excellent outcomes between the graft only and augment groups (67% vs. 75%, p > 0.99). CONCLUSION: Anatomical reduction of the AC joint and reconstruction CC ligaments are crucial for optimal joint stability and function. Two-tunnel CC reconstruction with an allogenous ST graft provides superior significantly better radiographic and clinical results compared to the single-tunnel reconstruction technique. PMID- 25127716 TI - Involvement of the chemokine CCL3 and the purinoceptor P2X7 in the spinal cord in paclitaxel-induced mechanical allodynia. AB - BACKGROUND: Paclitaxel is an effective chemotherapeutic agent widely used for the treatment of solid tumors. The major dose-limiting toxicity of paclitaxel is peripheral neuropathy. The mechanisms underlying the development and maintenance of paclitaxel-induced peripheral neuropathy are still unclear, and there are no currently established effective treatments. Accumulating evidence in models of neuropathic pain in which peripheral nerves are lesioned has implicated spinal microglia and chemokines in pain hypersensitivity, but little is know about their roles in chemotherapy-induced peripheral neuropathy. In the present study, we investigated the role of CC-chemokine ligand 3 (CCL3) in the spinal cord in the development and maintenance of mechanical allodynia using a rat model of paclitaxel-induced neuropathy. FINDINGS: Repeated intravenous administration of paclitaxel induced a marked decrease in paw withdrawal threshold in response to mechanical stimulation (mechanical allodynia). In these rats, the number of microglia in the spinal dorsal horn (SDH) was significantly increased. Paclitaxel treated rats showed a significant increase in the expression of mRNAs for CCL3 and its receptor CCR5 in the SDH. Intrathecal administration of a CCL3 neutralizing antibody not only attenuated the development of paclitaxel-induced mechanical allodynia but also reversed its maintenance. Paclitaxel also upregulated expression of purinoceptor P2X7 receptors (P2X7Rs), which have been implicated in the release of CCL3 from microglia, in the SDH. The selective P2X7R antagonist A438079 had preventive and reversal effects on paclitaxel-induced allodynia. CONCLUSIONS: Our findings suggest a contribution of CCL3 and P2X7Rs in the SDH to paclitaxel-induced allodynia and may provide new therapeutic targets for paclitaxel-induced painful neuropathy. PMID- 25127717 TI - The efficacy-effectiveness distinction in trials of alcohol brief intervention. AB - Three recent sets of null findings from trials of alcohol brief intervention (BI) have been disappointing to those who wish to see a reduction in alcohol-related harm through the widespread dissemination of BI. Saitz (7) has suggested that these null findings result from a failure to translate the effects of BI seen in efficacy trials, which are thought to contribute mainly to the beneficial effects of BI shown in meta-analyses, to effectiveness trials conducted in real-world clinical practice. The present article aims to: (i) clarify the meaning of the terms "efficacy" and "effectiveness" and other related concepts; (ii) review the method and findings on efficacy-effectiveness measurement in the 2007 Cochrane Review by Kaner and colleagues; and (iii) make suggestions for further research in this area. Conclusions are: 1) to avoid further confusion, terms such as "efficacy trial", "effectiveness trial", "clinical representativeness", etc. should be clearly defined and carefully used; 2) applications of BI to novel settings should begin with foundational research and developmental studies, followed by efficacy trials, and political pressures for quick results from premature effectiveness trials should be resisted; 3) clear criteria are available in the literature to guide progress from efficacy research, through effectiveness research, to dissemination in practice; 4) to properly interpret null findings from effectiveness studies, it is necessary to ensure that interventions are delivered as intended; 5) in future meta-analyses of alcohol BI trials, more attention should be paid to the development and application of a psychometrically robust scale to measure efficacy-effectiveness or clinical representativeness; 6) the null findings under consideration cannot be firmly attributed to a failure to translate effects from efficacy trials to real-world practice, because it is possible that the majority of trials included in meta analyses on which the evidence for the beneficial effects of alcohol BI was based tended to be effectiveness rather than efficacy trials; and 7) a hypothesis to explain the null findings in question is that they are due to lack of fidelity in the implementation of BI in large, organizationally complex, cluster randomized trials. PMID- 25127718 TI - Annona muricata leaves induced apoptosis in A549 cells through mitochondrial mediated pathway and involvement of NF-kappaB. AB - BACKGROUND: Annona muricata leaves have been reported to have antiproliferative effects against various cancer cell lines. However, the detailed mechanism has yet to be defined. The current study was designed to evaluate the molecular mechanisms of A. muricata leaves ethyl acetate extract (AMEAE) against lung cancer A549 cells. METHODS: The effect of AMEAE on cell proliferation of different cell lines was analyzed by MTT assay. High content screening (HCS) was applied to investigate the suppression of NF-kappaB translocation, cell membrane permeability, mitochondrial membrane potential (MMP) and cytochrome c translocation from mitochondria to cytosol. Reactive oxygen species (ROS) formation, lactate dehydrogenase (LDH) release and activation of caspase-3/7, -8 and -9 were measured while treatment. The western blot analysis also carried out to determine the protein expression of cleaved caspase-3 and -9. Flow cytometry analysis was used to determine the cell cycle distribution and phosphatidylserine externalization. Quantitative PCR analysis was performed to measure the gene expression of Bax and Bcl-2 proteins. RESULTS: Cell viability analysis revealed the selective cytotoxic effect of AMEAE towards lung cancer cells, A549, with an IC50 value of 5.09 +/- 0.41 MUg/mL after 72 h of treatment. Significant LDH leakage and phosphatidylserine externalization were observed in AMEAE treated cells by fluorescence analysis. Treatment of A549 cells with AMEAE significantly elevated ROS formation, followed by attenuation of MMP via upregulation of Bax and downregulation of Bcl-2, accompanied by cytochrome c release to the cytosol. The incubation of A549 cells with superoxide dismutase and catalase significantly attenuated the cytotoxicity caused by AMEAE, indicating that intracellular ROS plays a pivotal role in cell death. The released cytochrome c triggered the activation of caspase-9 followed by caspase-3. In addition, AMEAE-induced apoptosis was accompanied by cell cycle arrest at G0/G1 phase. Moreover, AMEAE suppressed the induced translocation of NF-kappaB from cytoplasm to nucleus. CONCLUSIONS: Our data showed for the first time that the ethyl acetate extract of Annona muricata inhibited the proliferation of A549 cells, leading to cell cycle arrest and programmed cell death through activation of the mitochondrial-mediated signaling pathway with the involvement of the NF-kB signalling pathway. PMID- 25127719 TI - Particle beam radiation therapy using carbon ions and protons for oligometastatic lung tumors. AB - BACKGROUND: A study was undertaken to analyze the efficacy and feasibility of particle beam radiation therapy (PBRT) using carbon ions and protons for the treatment of patients with oligometastatic lung tumors. METHODS: A total of 47 patients with 59 lesions who underwent PBRT for oligometastatic lung tumors between 2003 and 2011 were included in this study. Patient median age was 66 (range, 39-84) years. The primary tumor site was the colorectum in 11 patients (23.4%), lung in 10 patients (21.3%) and a variety of other sites in 26 patients (55.3%). Thirty-one patients (66%) received chemotherapy prior to PBRT. Thirty three lesions were treated with 320-MeV carbon ions and 26 were treated with 150- or 210-Mev protons in 1-4 portals. A median total dose of 60 (range, 52.8-70.2) GyE was delivered at the isocenter in 8 (range, 4-26) fractions. RESULTS: The median follow-up time was 17 months. The local control, overall survival and progression-free survival rates at 2 years were 79%, 54 and 27% respectively. PBRT-related toxicities were observed; six patients (13%) had grade 2 toxicity (including grade 2 radiation pneumonitis in 2) and six patients (13%) had grade 3 toxicity. Univariate analysis indicated that patients treated with a biologically equivalent dose of 10 (BED10) <110 GyE10, had a significantly higher local recurrence rate. Local control rates were relatively lower in the subsets of patients with the colorectum as the primary tumor site. No local progression was observed in metastases from colorectal cancer irradiated with a BED10 >= 110 GyE10. There was no difference in treatment results between proton and carbon ion therapy. CONCLUSIONS: PRBT is well tolerated and effective in the treatment of oligometastatic lung tumors. To further improve local control, high-dose PBRT with a BED10 >= 110 GyE10 may be promising. Further investigation of PBRT for lung oligometastases is warranted. PMID- 25127720 TI - The Namaqua rock mouse (Micaelamys namaquensis) as a potential reservoir and host of arthropod vectors of diseases of medical and veterinary importance in South Africa. AB - BACKGROUND: The role of endemic murid rodents as hosts of arthropod vectors of diseases of medical and veterinary significance is well established in the northern hemisphere. In contrast, endemic murids are comparatively understudied as vector hosts in Africa, particularly in South Africa. Considering the great rodent diversity in South Africa, many of which may occur as human commensals, this is unwarranted. METHODS: In the current study we assessed the ectoparasite community of a widespread southern African endemic, the Namaqua rock mouse (Micaelamys namaquensis), that is known to carry Bartonella spp. and may attain pest status. We aimed to identify possible vectors of medical and/or veterinary importance which this species may harbour and explore the contributions of habitat type, season, host sex and body size on ectoparasite prevalence and abundance. RESULTS: Small mammal abundance was substantially lower in grasslands compared to rocky outcrops. Although the small mammal community comprised of different species in the two habitats, M. namaquensis was the most abundant species in both habitat types. From these 23 ectoparasite species from four taxa (fleas, ticks, mites and lice) were collected. However, only one flea (Xenopsylla brasiliensis) and one tick species (Haemaphysalis elliptica) have a high zoonotic potential and have been implicated as vectors for Yersinia pestis and Bartonella spp. and Rickettsia conorii, respectively. The disease status of the most commonly collected tick (Rhipicephalus distinctus) is currently unknown. Only flea burdens differed markedly between habitat types and increased with body size. With the exception of lice, all parasite taxa exhibited seasonal peaks in abundance during spring and summer. CONCLUSION: M. namaquensis is the dominant small mammal species irrespective of habitat type. Despite the great ectoparasite diversity harboured by M. namaquensis, only a small number of these are known as vectors of diseases of medical and/or veterinary importance but occur at high prevalence and/or abundance. This raises concern regarding the potential of this host as an endemic reservoir for zoonotic diseases. Consequently, additional sampling throughout its distributional range and research addressing the role of M. namaquensis as a reservoir for zoonotic diseases in southern Africa is urgently needed. PMID- 25127721 TI - Visualization of the physical and functional interaction between hMYH and hRad9 by Dronpa bimolecular fluorescence complementation. AB - BACKGROUND: Human MutY glycosylase homolog (hMYH), a component of the base excision repair pathway, is responsible for the generation of apurinic/apyrimidinic sites. Rad9-Rad1-Hus1 (9-1-1) is a heterotrimeric protein complex that plays a role in cell cycle checkpoint control and DNA repair. In humans, hMYH and 9-1-1 interact through Hus1 and to a lesser degree with Rad1 in the presence of DNA damage. In Saccharomyces pombe, each component of the 9-1-1 complex interacts directly with SpMYH. The glycosylase activity of hMYH is stimulated by Hus1 and the 9-1-1 complex and enhanced by DNA damage treatment. Cells respond to different stress conditions in different manners. Therefore, we investigated whether Rad9 interacted with hMYH under different stresses. Here, we identified and visualized the interaction between hRad9 and hMYH and investigated the functional consequences of this interaction. RESULTS: Co-IP and BiFC indicates that hMYH interacts with hRad9. As shown by GST-pull down assay, this interaction is direct. Furthermore, BiFC with deletion mutants of hMYH showed that hRad9 interacts with N-terminal region of hMYH. The interaction was enhanced by hydroxyurea (HU) treatment. mRNA and protein levels of hMYH and hRad9 were increased following HU treatment. A marked increase in p-Chk1 (S345) and p-Cdk2 (T14, Y15) was observed. But this phosphorylation decreased in siMYH- or siRad9 transfected cells, and more pronounced decrease observed in co-transfected cells. CONCLUSIONS: Our data reveal that hRad9 interacts directly with N-terminal region of hMYH. This interaction is enhanced by HU treatment. Knockdown of one or both protein result in decreasing Chk1 and Cdk2 phosphorylation. Since both protein functions in the early detection of DNA damage, we suggest that this interaction occurs early in DNA damage pathway. PMID- 25127722 TI - Assessment of retention force and bone apposition in two differently coated femoral stems after 6 months of loading in a goat model. AB - BACKGROUND: Since the introduction of uncemented hip implants, there has been a search for the best surface coating to enhance bone apposition in order to improve retention. The surface coating of the different stems varies between products. The aim was to assess the retention force and bone adaption in two differently coated stems in a weight-bearing goat model. MATERIALS AND METHODS: Hydroxyapatite (HA) and electrochemically deposited calcium phosphate (CP; Bonit) on geometrically comparable titanium-based femoral stems were implanted into 12 (CP group) and 35 (HA group) goats. The animal model included physiological loading of the implants for 6 months. The pull-out force of the stems was measured, and bone apposition was microscopically evaluated. RESULTS: After exclusion criteria were applied, the number of available goats was 4 in the CP group and 11 in the HA group. The CP-coated stems had significantly lower retention forces compared with the HA-coated ones after 6 months (CP median 47 N, HA median 1,696 N, p = 0.003). Bone sections revealed a lower degree of bone apposition in the CP-coated stems, with more connective tissue in the bone/implant interface compared with the HA group. CONCLUSION: In this study, HA had better bone apposition and needed greater pull-out force in loaded implants. The application of CP on the loaded titanium surface to enhance the apposition of bone is questioned. PMID- 25127723 TI - Proximal and distal determinants of stressful work: framework and analysis of retrospective European data. AB - BACKGROUND: While robust evidence on associations of stressful work with health exists, less research is available on determinants of stressful work in terms of respondents' characteristics (proximal factors) and in terms of national labour market policies (distal factors). In this article we analyse proximal (childhood circumstances and labour market disadvantage) and distal determinants (national compensation and integration policies) of stressful work in a comprehensive framework. METHODS: We use data from the third wave of the Survey of Health, Ageing and Retirement in Europe (SHARE), with retrospective information on individual life courses collected among 11181 retired men and women in 13 European countries (2008-2009). To test our hypotheses we estimate multilevel regression models. RESULTS: Results show that stressful work is related to disadvantaged circumstances during childhood. To some extent this association is explained by labour market disadvantage during adulthood. Additionally, well developed labour market integration policies are related to lower overall levels of stressful work at national level. CONCLUSION: This analysis provides first evidence of important determinants of stressful work, both in terms of pre employment conditions (childhood circumstances) and in terms of contextual macro social policies. PMID- 25127724 TI - miRNA expression profiles in cerebrospinal fluid and blood of patients with acute ischemic stroke. AB - The aims of the study were (1) to determine whether miRNAs (microRNAs) can be detected in the cerebrospinal fluid (CSF) and blood of patients with ischemic stroke and (2) to compare these miRNA profiles with corresponding profiles from other neurological patients to address whether the miRNA profiles of CSF or blood have potential usefulness as diagnostic biomarkers of ischemic stroke. CSF from patients with acute ischemic stroke (n = 10) and patients with other neurological diseases (n = 10) was collected by lumbar puncture. Blood samples were taken immediately after. Expression profiles in the cell-free fractions of CSF and blood were analyzed by a microarray technique (miRCURY LNATM microRNA Array, Exiqon A/S, Denmark) using a quantitative PCR (qPCR) platform containing 378 miRNA primers. In total, 183 different miRNAs were detected in the CSF, of which two miRNAs (let-7c and miR-221-3p) were found upregulated in relation to stroke. In the blood, 287 different miRNAs were detected of which two miRNAs (miR-151a-3p and miR-140-5p) were found upregulated and one miRNA (miR-18b-5p) was found downregulated in the stroke group. Some miRNAs occurred exclusively in the CSF including miR-523-3p which was detected in 50 % of the stroke patients, whereas it was completely absent in controls. Our preliminary results demonstrate that it is possible to detect and profile miRNAs in CSF and blood from patients with neurological diseases. Some miRNAs appear differentially expressed in the CSF and others in the blood of stroke patients. Currently, we are validating our results in larger groups of patients. PMID- 25127726 TI - Mass effect from hepatomegaly in polycystic kidney disease. PMID- 25127727 TI - Capsule commentary on Larochelle et al., Reducing excess biomarker testing at an academic medical center. PMID- 25127725 TI - Intensive blood pressure control, falls, and fractures in patients with type 2 diabetes: the ACCORD trial. AB - BACKGROUND: There are few rigorous studies to confirm or refute the commonly cited concern that control of blood pressure to lower thresholds may result in an increased risk of falls and fractures. OBJECTIVE: To compare falls and fractures in participants with type 2 diabetes in the intensive (targeting a systolic blood pressure of < 120 mmHg) and standard (targeting a systolic blood pressure of < 140 mmHg) blood pressure control arms of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial (N = 4,733). PARTICIPANTS: A subset of 3,099 participants self-reported annually on the occurrence of falls and non spine fractures. Fractures were centrally adjudicated. MAIN MEASURES: The incidence of falls in the two treatment groups was compared using a random effects negative binomial model, and fracture risk was compared using Cox proportional hazards models. KEY RESULTS: At enrollment in both groups, the mean age was 62 years, 44% were women, 25% were Black, and mean blood pressure was 138/75 mmHg. During follow-up, all classes of medications, particularly thiazide diuretics, were more commonly prescribed in the intensive group. After 1 year of follow-up, the mean systolic blood pressure was 133 +/- 15 mmHg in the standard group and 119 +/- 14 mmHg in the intensive group. The adjusted rate of falls did not differ in the intensive and standard groups (62.2/100 person-years vs. 74.1/100 person-years, RR = 0.84, 95% CI 0.54-1.29, p = 0.43). The risk of non spine fractures was nonsignificantly lower in the intensive than in the standard blood pressure group (HR 0.79, 95% CI 0.62-1.01, p = 0.06). CONCLUSIONS: We conclude that intensive antihypertensive treatment that lowered mean systolic blood pressure to below 120 mmHg was not associated with an increased risk of falls or non-spine fractures in patients age 40 to 79 years with type 2 diabetes. PMID- 25127729 TI - Capsule commentary on Marc et al., Reliability and validity of the Haitian Creole PHQ-9. PMID- 25127728 TI - Geographic and racial/ethnic variations in patterns of multimorbidity burden in patients with type 2 diabetes. AB - BACKGROUND: Multimorbidity presents a significant public health challenge, but regional, rural/urban, and racial/ethnic differences in patterns of multimorbidity in diabetes are poorly understood. OBJECTIVE: To describe patterns of multimorbidity in medical and mental health by regional, rural/urban, and racial/ethnic variation in patients with type 2 diabetes mellitus. DESIGN: Retrospective cohort study from 2002 through 2006 PARTICIPANTS: A national cohort of 892,223 veterans with diabetes MAIN MEASURES: Multimorbidity was the main outcome defined as: the measure of multimorbidity and two categorical outcomes, with pattern of medical and mental health comorbidities combined and separately. KEY RESULTS: Among patients, 52% had 2+ comorbidities, 33% had a single comorbidity, and 14% had no comorbidity; 13.9% had both medical and mental health comorbidities, 70.3% had medical only, and 1.5% had mental health only. The odds of having 3+ comorbidities were nearly fourfold greater in patients 75 years and older relative to patients younger than 50 years (OR=3.95 [95% CI: 3.84, 4.06]). Compared to non-Hispanic whites, the odds of 3+ comorbidities among non-Hispanic blacks were 1.67 times greater (95% CI: 1.63, 1.71). Hispanics were more likely to have a mental health comorbidity alone (OR=1.20 [95% CI: 1.13, 1.28]) than non Hispanic whites. For patients living in rural areas, the odds were higher of having 3+ comorbidities (OR=1.21 [95% CI: 1.19, 1.23]) and of having both medical and mental health comorbidities (OR=1.15 [95% CI: 1.13, 1.17]) compared to urban dwellers. CONCLUSIONS: Among individuals with diabetes, traditionally disadvantaged groups, including non-Hispanic blacks and rural patients, appear to bear the greatest burden and risk of multimorbidity. Significantly greater odds with increasing number of comorbidities were seen by race/ethnicity, rural residence, and geographic region. PMID- 25127730 TI - Tackling disparities in influenza vaccination in primary care: it takes a team. PMID- 25127732 TI - Osteometric analysis for sexing of modern sternum - an autopsy study from South India. AB - Estimation of sex is considered as one of the essential parameters in forensic anthropology and requires foremost attention in the analysis of commingled and unidentified remains. In India, there is a paucity of population specific morphometric standards for identifying sex from unknown human remains in different population groups. The present research is an osteometric analysis to study the sexual dimorphism of the sternum of South Indian origin using statistical considerations. The study sample constituted of adult autopsied sternums of known age and sex. Five linear measurements (length of the manubrium, mesosternum, manubrium and mesosternum together, and width at 1st and at 3rd sternebra) were examined during the study. Three indices (manubrio-corpus Index, ratio of the length of the mesosternum and manubrium, and sternubrial-width index) were computed from the length and width measurements of the sternum. Statistical analysis was done using SPSS computer software and Student's t-test was applied to find the sex differences in these variables. While statistically significant sex differences were observed for all the five linear measurements of the sternum, none of the sternal indices showed statistically significant sex differences. Discriminant function and logistic regression analysis were performed to derive the predicting models for estimation of sex from the different variables. The predictability of sternal measurements in sexing using univariate models ranged between 67.5% for the width at 3rd sternebra and 74.4% for the combined length of manubrium and mesosternum. The classification accuracy rates of sternal measurements were observed to be higher when multivariate analysis was performed. Length of manubrium and mesosternum together along with width at 1st sternebra yielded maximum accuracy of 79.5% (discriminant function analysis) and 81.2% (logistic regression analysis) in sexing of male and female sternum. The present research concludes that the application of sternum in sex estimation should be restricted to cases when other more reliable bones for sexing are not available to the investigators. PMID- 25127733 TI - Synthesis and characterization of antifouling poly(N-acryloylaminoethoxyethanol) with ultralow protein adsorption and cell attachment. AB - Rational design of effective antifouling polymers is challenging but important for many fundamental and applied applications. Herein we synthesize and characterize an N-acryloylaminoethoxyethanol (AAEE) monomer, which integrates three hydrophilic groups of hydroxyl, amide, and ethylene glycol in the same material. AAEE monomers were further grafted and polymerized on gold substrates to form polyAAEE brushes with well-controlled thickness via surface-initiated atomic transfer radical polymerization (SI-ATRP), with particular attention to a better understanding of the molecular structure-antifouling property relationship of hydroxyl-acrylic-based polymers. The surface hydrophilicity and antifouling properties of polyAAEE brushes as a function of film thickness are studied by combined experimental and computational methods including surface plasmon resonance (SPR) sensors, atomic force microscopy (AFM), cell adhesion assay, and molecular dynamics (MD) simulations. With the optimal polymer film thicknesses (~10-40 nm), polyAAEE-grafted surfaces can effectively resist protein adsorption from single-protein solutions and undiluted human blood plasma and serum to a nonfouling level (i.e., <0.3 ng/cm(2)). The polyAAEE brushes also highly resist mammalian cell attachment up to 3 days. MD simulations confirm that the integration of three hydrophilic groups induce a stronger and closer hydration layer around polyAAEE, revealing a positive relationship between surface hydration and antifouling properties. The molecular structure-antifouling properties relationship of a series of hydroxyl-acrylic-based polymers is also discussed. This work hopefully provides a promising structural motif for the design of new effective antifouling materials beyond traditional ethylene glycol based antifouling materials. PMID- 25127731 TI - Interest in genetic testing in Ashkenazi Jewish Parkinson's disease patients and their unaffected relatives. AB - Our objective was to explore interest in genetic testing among Ashkenazi Jewish (AJ) Parkinson's Disease (PD) cases and first-degree relatives, as genetic testing for LRRK2 G2019S is widely available. Approximately 18 % of AJ PD cases carry G2019S mutations; penetrance estimations vary between 24 and 100 % by age 80. A Genetic Attitude Questionnaire (GAQ) was administered at two New York sites to PD families unaware of LRRK2 G2019S mutation status. The association of G2019S, age, education, gender and family history of PD with desire for genetic testing (outcome) was modeled using logistic regression. One-hundred eleven PD cases and 77 relatives completed the GAQ. Both PD cases and relatives had excellent PD-specific genetic knowledge. Among PD, 32.6 % "definitely" and 41.1 % "probably" wanted testing, if offered "now." Among relatives, 23.6 % "definitely" and 36.1 % "probably" wanted testing "now." Desire for testing in relatives increased incrementally based on hypothetical risk of PD. The most important reasons for testing in probands and relatives were: if it influenced medication response, identifying no mutation, and early prevention and treatment. In logistic regression, older age was associated with less desire for testing in probands OR = 0.921 95%CI 0.868-0.977, p = 0.009. Both probands and relatives express interest in genetic testing, despite no link to current treatment or prevention. PMID- 25127734 TI - Re-description of a genetically typed, single oocyst line of the turkey coccidium, Eimeria adenoeides Moore and Brown, 1951. AB - The Guelph strain of Eimeria adenoeides was obtained from a commercial turkey flock in Ontario, Canada, in 1985. Single oocyst derived lines of E. adenoeides were propagated, and one of them used to re-describe biological and morphological features of E. adenoeides in the turkey. Oocysts of this strain are within the lower size ranges in the original species description reported by Moore and Brown (1951); oocysts of the Guelph strain averaged 18.7 +/- 1.4 MUm (16.7-22.5) by 14.3 +/- 0.9 MUm (13-16.2, n = 30) with a shape index (SI) of 1.3 +/- 0.1. It is possible that the original species description was based, at least in part, on a mixed culture of two or more Eimeria species. Immature first-generation meronts of E. adenoeides Guelph strain were observed histologically at 32 h post infection in the ileum and cecal neck. Early studies reported only two asexual generations suggested that first asexual cycle observed at 32 h post-infection was overlooked. In the present study, three asexual generations were observed before the start of gametogony. The Guelph strain is also characterized by a prepatent period of 112 h. The Guelph strain of E. adenoeides is a highly pathogenic coccidium that forms classic cecal lesions, including prominent caseous cecal cores, during moderate to severe infections. The maximum output of oocysts (1.77 * 10(7) per bird) was obtained from birds inoculated with 1 * 10(3) oocysts; maximum fecundity (1.55 * 10(5) oocyst shed per oocyst inoculated) was obtained with an inoculation of 1 * 10(2) oocysts, but fecundity dropped dramatically as the inoculation dose increased. To promote stability of the E. adenoeides species concept, neotype specimens (a parahapantotype slides series and phototype) have been designated and deposited for future reference. PMID- 25127735 TI - Influence of environmental factors on Argulus japonicus occurrence of Guangdong province, China. AB - To assess the effects of abiotic factors on Argulus japonicus occurrence in freshwater ecosystem, we sampled fish, free-swimming parasites, and submerged objects from rivers, fish farms, and ponds (reservoirs and lakes) at 27 locations in Guangdong province, China, from July, 2010, to March, 2013. Friedman's test and Spearman's correlation coefficient (r) were used to investigate relationship between A. japonicus occurrence and abiotic factors in three aquatic systems. Correlation of monthly density, mean density, prevalence, abundance, and intensity of A. japonicus with water temperature, biochemical oxygen demand of 5 days, chemical oxygen demand, and ammonia were very significant, but negative relation with pH, dissolved oxygen, and total phosphorus components. Nevertheless, total nitrogen components showed an insignificant impact on A. japonicus incidence. In addition, water temperature and stability were two key factors controlling A. japonicus infestation. Our study revealed the capability of A. japonicus to inhabit and prevail in heavily polluted freshwater. Results demonstrate that A. japonicus has good adaptability to the environmental factors' stress but cannot be used as a biological indicator of environmental pollution. PMID- 25127737 TI - An analysis of historical Mussel Watch Programme data from the west coast of the Cape Peninsula, Cape Town. AB - The concentrations of metals in the mussel Mytilus galloprovincialis (Lamarck, 1819) prevalent along the west coast of the Cape Peninsula, Cape Town are presented. The mussels were sampled during the routine "Mussel Watch Programme" (MWP) between 1985 and 2008. Levels of Cu, Cd, Pb, Zn, Hg, Fe and Mn at Cape Point, Hout Bay, Sea Point, Milnerton and Bloubergstrand were analysed for autumn and spring and showed consistent similar mean values for the five sites. There was a highly significant temporal (annual and seasonal) difference between all metals as well as a significant difference in metal concentrations between the five sites. The concentrations of Zn, Fe, Cd and Pb were higher than previous investigations and possibly indicative of anthropogenic sources of metals. The results provide a strong motivation to increase efforts in marine pollution research in the area. PMID- 25127736 TI - Identity of rumen fluke in deer. AB - As evidence is growing that in many temperate areas paramphistome infections are becoming more common and widespread, this study was undertaken to determine the role of deer as reservoirs for rumen fluke infections in livestock. A total of 144 deer faecal samples (88 from fallow deer, 32 from red deer and 24 samples from sika, sika/red deer hybrids) were screened for the presence of fluke eggs. Based on the ITS-2 rDNA locus plus flanking 5.8S and 28S sequences (ITS-2+), fluke eggs were identified to species level. Our results indicate that, of the 3 deer species, fallow deer had the highest fluke infection rates. Two rumen fluke species, Calicophoron daubneyi and Paramphistomum leydeni, with morphologically distinct eggs, were identified. Concurrent infections of the two paramphistome species and liver fluke, Fasciola hepatica, were common. Considering the comparatively low egg burdens observed in this study, it is unlikely that deer represent a significant source of infection for Irish livestock. PMID- 25127738 TI - Thyroid hormone regulation of hepatic lipid and carbohydrate metabolism. AB - Thyroid hormone (TH) has important roles in regulating hepatic lipid, cholesterol, and glucose metabolism. Recent findings suggest that clinical conditions such as non-alcoholic fatty liver disease and type 2 diabetes mellitus, which are associated with dysregulated hepatic metabolism, may involve altered intracellular TH action. In addition, TH has key roles in lipophagy in lipid metabolism, mitochondrial quality control, and the regulation of metabolic genes. In this review, we discuss recent findings regarding the functions of TH in hepatic metabolism, the relationship between TH and metabolic disorders, and the potential therapeutic use of thyromimetics to treat metabolic dysfunction in the liver. PMID- 25127740 TI - Social class across the life course and physical activity at age 34 years in the 1970 British birth cohort. AB - PURPOSE: To examine the associations between social class at ages 0, 5, 10, 30, and 34 years and physical activity at age 34 years using a novel approach to analysis of life course data. METHODS: We used structural equation modeling to compare three competing models in life course epidemiology: the accumulation of risk model with additive effects, the accumulation of risk model with trigger effect, and the critical period model. Data were from a nationally representative prospective cohort of 16,571 British men and women born in 1970. Outcomes were physical activity during leisure time, during transports, and at work. RESULTS: For all three domains of physical activity, for men and women, the accumulation of risk model with additive effects fit the data best. In this model, social class at ages 0, 5, 10, 30, and 34 years were associated with physical activity at age 34 years, although the magnitude and the direction of the associations for social class at each age varied by physical activity outcome and by sex. CONCLUSIONS: Structural equation modeling appears to be a helpful tool in selecting among competing models in life course epidemiology. PMID- 25127739 TI - First-trimester nonsystemic corticosteroid use and the risk of oral clefts in Norway. AB - PURPOSE: Exposure of pregnant mice to corticosteroids can produce oral clefts in offspring. Although data in humans are more mixed, recent reports have suggested that dermatologic steroids are associated with oral clefts. METHODS: We investigated maternal first-trimester exposure to corticosteroids (focusing on dermatologic uses) and oral clefts in offspring using two population-based studies. The Norway Cleft Study (1996-2001) is a national case-control study including 377 infants with cleft lip +/- palate (CLP), 196 infants with cleft palate only (CPO), and 763 controls. The Norwegian Mother and Child Cohort Study (MoBa, 1998-2008) is a national birth cohort including 123 infants with CLP, 61 infants with CPO, and 551 controls. RESULTS: In the case-control study, there was the suggestion of an association of dermatologic corticosteroids with both CLP (adjusted OR [aOR], 2.3; 95% confidence interval [CI], 0.71-7.7) and CPO (aOR, 3.4; CI, 0.87-13). There was no evidence of this association in the cohort data (odds ratio for CLP, 1.2; CI, 0.50-2.8 and odds ratio for CPO, 1.0; CI, 0.30 3.4), although exposure to dermatologic steroids was less specifically ascertained. There were no associations with other types of corticosteroids. CONCLUSIONS: Our data add to the suggestive but inconsistent findings for this association. PMID- 25127742 TI - In vivo hippocampal subfield volumes in schizophrenia and bipolar disorder. AB - BACKGROUND: Hippocampal dysfunction and volume reductions have been reported in patients with schizophrenia and bipolar disorder. The hippocampus consists of anatomically distinct subfields. We investigated to determine whether in vivo volumes of hippocampal subfields differ between clinical groups and healthy control subjects. METHODS: Clinical examination and magnetic resonance imaging were performed in 702 subjects (patients with schizophrenia spectrum [n = 210; mean age, 32.0 +/- 9.3 (SD) years; 59% male], patients with bipolar spectrum [n = 192; mean age, 35.5 +/- 11.5 years; 40% male] and healthy control subjects [n = 300; mean age, 35.3 +/- 9.9 years; 53% male]). Hippocampal subfield volumes were estimated with FreeSurfer. General linear models were used to explore diagnostic differences in hippocampal subfield volumes, covarying for age, intracranial volume, and medication. Post hoc analyses of associations to psychosis symptoms (Positive and Negative Syndrome Scale) and cognitive function (verbal memory [California Verbal Learning Test, second edition] and IQ [Wechsler Abbreviated Scale of Intelligence]) were performed. RESULTS: Patient groups had smaller cornu ammonis (CA) subfields CA2/3 (left, p = 7.2 * 10(-6); right, p = 2.3 * 10(-6)), CA4/dentate gyrus (left, p = 1.4 * 10(-5); right, p = 2.3 * 10(-6)), subiculum (left, p = 3.7 * 10(-6); right, p = 2.8 * 10(-8)), and right CA1 (p = .006) volumes than healthy control subjects, but smaller presubiculum volumes were found only in patients with schizophrenia (left, p = 6.7 * 10(-5); right, p = 1.6 * 10(-7)). Patients with schizophrenia had smaller subiculum (left, p = .035; right, p = .031) and right presubiculum (p = .002) volumes than patients with bipolar disorder. Smaller subiculum volumes were related to poorer verbal memory in patients with bipolar disorder and healthy control subjects and to negative symptoms in patients with schizophrenia. CONCLUSIONS: Hippocampal subfield volume reductions are found in patients with schizophrenia and bipolar disorder. The magnitude of reduction is greater in patients with schizophrenia, particularly in the hippocampal outflow regions presubiculum and subiculum. PMID- 25127741 TI - Neonatal maternal separation alters the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter. AB - BACKGROUND: Early life stress is thought to contribute to psychiatric disorders, but the precise mechanisms underlying this link are poorly understood. As neonatal stress decreases adult hippocampal neurogenesis, which, in turn, functionally contributes to many behavioral phenotypes relevant to psychiatric disorders, we examined how in vivo neonatal maternal separation (NMS) impacts the capacity of adult hippocampal neural precursor cells via epigenetic alterations in vitro. METHODS: Rat pups were separated from their dams for 3 hours daily from postnatal day (PND) 2 to PND 14 or were never separated from the dam (as control animals). We isolated adult neural precursor cells from the hippocampal dentate gyrus at PND 56 and assessed rates of proliferation, apoptosis, and differentiation in cell culture. We also evaluated the effect of DNA methylation at the retinoic acid receptor (RAR) promoter stemming from NMS on adult neural precursor cells. RESULTS: NMS attenuated neural differentiation of adult neural precursor cells but had no detectible effect on proliferation, apoptosis, or astroglial differentiation. The DNA methyltransferase (DNMT) inhibitor, 5-aza-dC, reversed a reduction by NMS of neural differentiation of adult neural precursor cells. NMS increased DNMT1 expression and decreased expression of RARalpha. An RARalpha agonist increased neural differentiation and an antagonist reduced retinoic acid-induced neural differentiation. NMS increased the methylated portion of RARalpha promoter, and the DNMT inhibitor reversed a reduction by NMS of RARalpha messenger RNA expression. CONCLUSIONS: NMS attenuates the capacity of adult hippocampal neural precursor cells to differentiate into neurons by decreasing expression of RARalpha through DNMT1-mediated methylation of its promoter. PMID- 25127744 TI - NAD homeostasis in the bacterial response to DNA/RNA damage. AB - In mammals, NAD represents a nodal point for metabolic regulation, and its availability is critical to genome stability. Several NAD-consuming enzymes are induced in various stress conditions and the consequent NAD decline is generally accompanied by the activation of NAD biosynthetic pathways to guarantee NAD homeostasis. In the bacterial world a similar scenario has only recently begun to surface. Here we review the current knowledge on the involvement of NAD homeostasis in bacterial stress response mechanisms. In particular, we focus on the participation of both NAD-consuming enzymes (DNA ligase, mono(ADP-ribosyl) transferase, sirtuins, and RNA 2'-phosphotransferase) and NAD biosynthetic enzymes (both de novo, and recycling enzymes) in the response to DNA/RNA damage. As further supporting evidence for such a link, a genomic context analysis is presented showing several conserved associations between NAD homeostasis and stress responsive genes. PMID- 25127743 TI - Disruption of the potassium channel regulatory subunit KCNE2 causes iron deficient anemia. AB - Iron homeostasis is a dynamic process that is tightly controlled to balance iron uptake, storage, and export. Reduction of dietary iron from the ferric to the ferrous form is required for uptake by solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 (Slc11a2) into the enterocytes. Both processes are proton dependent and have led to the suggestion of the importance of acidic gastric pH for the absorption of dietary iron. Potassium voltage-gated channel subfamily E, member 2 (KCNE2), in combination with potassium voltage gated channel, KQT-like subfamily, member 1 (KCNQ1), form a gastric potassium channel essential for gastric acidification. Deficiency of either Kcne2 or Kcnq1 results in achlorhydia, gastric hyperplasia, and neoplasia, but the impact on iron absorption has not, to our knowledge, been investigated. Here we report that Kcne2-deficient mice, in addition to the previously reported phenotypes, also present with iron-deficient anemia. Interestingly, impaired function of KCNQ1 results in iron-deficient anemia in Jervell and Lange-Nielsen syndrome patients. We speculate that impaired function of KCNE2 could result in the same clinical phenotype. PMID- 25127745 TI - Bacterial colonization of the ovarian bursa in dogs with clinically suspected pyometra and in controls. AB - Septic peritonitis occurs relatively commonly in dogs. Secondary septic peritonitis is usually associated with perforation of intestines or infected viscera, such as the uterus in pyometra cases. The aim of this study was to evaluate the bacterial flora in the ovarian bursae of intact bitches as a potential source of contamination. One hundred forty dogs, clinically suspected of pyometra, were prospectively enrolled. The control group consisted of 26 dogs that underwent elective ovariohysterectomies and 18 dogs with mammary gland tumors that were neutered at the time of mastectomy. Bacteriology samples were taken aseptically at the time of surgery from the bursae and the uterus in all dogs. Twenty-two dogs that were clinically suspected of pyometra had sterile uterine content ("mucometra" cases); the remaining 118 had positive uterine cultures ("pyometra" cases) and septic peritoneal fluid was present in 10% of these cases. Of the 118 pyometra cases, 9 had unilateral and 15 had bilateral bacterial colonization of their ovarian bursae. However, the bacteria from the ovarian bursa were similar to those recovered from the uterine pus in only half of the cases. Furthermore, positive bursae were also seen in one mucometra dog (unilateral) and in four control dogs (two unilateral and two bilateral). The data illustrate that the canine ovarian bursa can harbor bacteria. The biological importance of these isolations remains unclear. PMID- 25127746 TI - [Alterations in arterial compliance of dyslipidemic patients]. AB - INTRODUCTION: We studied the alteration on the distensibility of the arterial walls caused by dyslipidemia LDLc dependent, along the decades of life, by means of a study of the radial artery pulse wave. METHODS: We made an analysis of the radial artery pulse wave records acquired by means a movement displacement sensor, placed on radial palpation area. We recruited 100 dyslipidemic men without other cardiovascular risk factors, between the 3rd and the 6th decade. We identified the reflected wave in the records and we computed the augmentation index in order to quantify its amplitude and position. This index is useful to assess the endothelial dysfunction. Besides, we defined a velocity coefficient as the ratio between the size of the individuals and the delay time between the peak of the systolic wave and the arrival of the reflected wave. Results were compared against those obtained in a group of 161 healthy volunteers. RESULTS: We found that dyslipidemic patients presented augmentation index values similar to controls until the fourth decade, increasing thereafter with significant differences only in the 6th decade. No significant differences were found in the velocity index in any of the ages studied. CONCLUSIONS: We conclude that alterations produced by dyslipidemia take decades to manifest, and they begin affecting the mechanism of vasodilation of distal arteries with highest proportion of smooth muscle, without altering the proximal conduit arteries with more elastin content. PMID- 25127747 TI - [Impact of plasma pro-B-type natriuretic peptide amino-terminal and galectin-3 levels on the predictive capacity of the LIPID Clinical Risk Scale in stable coronary disease]. AB - INTRODUCTION: At present, there is no tool validated by scientific societies for risk stratification of patients with stable coronary artery disease (SCAD). It has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1), galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have prognostic value in this population. OBJECTIVE: To analyze the prognostic value of a clinical risk scale published in Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) study and determining its predictive capacity when combined with plasma levels of MCP-1, galectin-3 and NT-proBNP in patients with SCAD. METHODS AND RESULTS: A total of 706 patients with SCAD and a history of acute coronary syndrome (ACS) were analyzed over a follow up period of 2.2 +/- 0.99 years. The primary endpoint was the occurrence of an ischemic event (any SCA, stroke or transient ischemic attack), heart failure, or death. A clinical risk scale derived from the LIPID study significantly predicted the development of the primary endpoint, with an area under the ROC curve (Receiver Operating Characteristic) of 0.642 (0.579 to 0.705); P<0.001. A composite score was developed by adding the scores of the LIPID and scale decile levels of MCP -1, galectin -3 and NT-proBNP. The predictive value improved with an area under the curve of 0.744 (0.684 to 0.805); P<0.001 (P=0.022 for comparison). A score greater than 21.5 had a sensitivity of 74% and a specificity of 61% for the development of the primary endpoint (P<0.001, log -rank test). CONCLUSION: Plasma levels of MCP-1, galectin -3 and NT-proBNP improve the ability of the LIPID clinical scale to predict the prognosis of patients with SCAD. PMID- 25127749 TI - Production of a value added compound from the H-acid waste water-Bioflocculants by Klebsiella pneumoniae. AB - A novel strain (designated as ZCY-7) which could convert H-acid into bioflocculants was isolated from H-acid wastewater sludge. Conditions for bioflocculants production were optimized by response surface methodology (RSM) and determined to be inoculum size 9.65%, initial pH 7.0, and CODCr of the H-acid wastewater 520mg/L. The highest flocculating efficiency achieved for kaolin suspension was 95.1%, after 60h cultivation. The yielded bioflocculant was mainly composed of polysaccharide (82.4%) and protein (14.2%), and maintained its flocculating activity in 0.4% (w/w) kaolin suspensions over pH 2-8 and 20-80 degrees C. Fourier transform infrared (FTIR) spectra showed that amino, amide and hydroxyl groups were present in the bioflocculant molecules. A viable alternative treatment technology of H-acid wastewater using this novel strain is suggested, which could largely reduce bioflocculants costs. In addition, flocculating mechanism investigation reveals that the bioflocculant could cause kaolin suspension instability by means of charge neutralization firstly and then promoted the aggregation of suspension particles by adsorption and bridge. It is evident from the results that H-acid wastewater could be used as a source to manufacture bioflocculants. PMID- 25127750 TI - The chloramphenicol acetyltransferase vector as a tool for stable tagging of Neospora caninum. AB - Neospora caninum is an obligate intracellular Apicomplexa, a phylum where one of the current methods for functional studies relies on molecular genetic tools. For Toxoplasma gondii, the first method described, in 1993, was based on resistance against chloramphenicol. As in T. gondii, we developed a vector constituted of the chloramphenicol acetyltransferase gene (CAT) flanked by the N. caninum dihydrofolate reductase-thymidylate synthase (DHFR-TS) 5' coding sequence flanking region. Five weeks after transfection and under the selection of chloramphenicol the expression of CAT increased compared to the wild type and the resistance was retained for more than one year. Between the stop codon of CAT and the 3' UTR of DHFR, a Lac-Z gene controlled by the N. caninum tubulin 5' coding sequence flanking region was ligated, resulting in a vector with a reporter gene (Ncdhfr-CAT/NcTub-tetO/Lac-Z). The stability was maintained through an episomal pattern for 14 months when the tachyzoites succumbed, which was an unexpected phenomenon compared to T. gondii. Stable parasites expressing the Lac-Z gene allowed the detection of tachyzoites after invasion by enzymatic reaction (CPRG) and were visualised macro- and microscopically by X-Gal precipitation and fluorescence. This work developed the first vector for stable expression of proteins based on chloramphenicol resistance and controlled exclusively by N. caninum promoters. PMID- 25127751 TI - Degradation of the mechanical properties of orthodontic NiTi alloys in the oral environment: an in vitro study. AB - Appropriate characterization studies are needed to demonstrate the mechanical and biological effects of interaction between archwires and the oral environment. The aim of this study was to investigate, in vitro, the impact of this acidic and fluoridated environment on the electrochemical behavior and the mechanical properties of orthodontic alloys in nickel titanium and in stainless steel (controls) for the following parameters: Young's modulus (E), elastic limit (sigmae) and the maximum tensile load (sigmam). Six samples of each archwire alloy were used to assess these parameters. An Instron universal test apparatus (model - 88512) was used for the traction tests on the wires after immersion in solutions at different concentrations of fluoride and at various pH levels. Observations were made using an electron scanning microscope (ESM) to evaluate the surface and an ICP (inductively coupled plasma) mass spectroscopy analysis was made to quantify the substances released into the immersion solution. For the NiTi archwires, immersion in the fluoridated and acidic medium showed a statistically significant reduction of the Young's modulus (E), the elastic limit (sigmae) and the maximum tensile load (sigmam). Similarly, a higher level of released nickel proportionate to the increase in the fluoride concentration and acidity was observed in the immersion solutions. ESM observations revealed the status of the surface of the different alloys and the presence of corrosive pitting. PMID- 25127753 TI - Dental sequellae of alveolar clefts: utility of endosseous implants. Part II: clinical cases. AB - This second part follows on from part 1 published in the previous issue of this journal. The aim of this publication is to offer teams specializing in the primary and secondary treatment of labio-alveolar-palatal clefts a prosthetic evaluation for more rational management of the dental sequellae of clefts for patients who, when they reach adulthood, often wish to improve their facial esthetics, in which the dental element plays an important part. The reorganization and restoration of the maxillary anterior teeth and their esthetic integration with respect to the face and lips would then be less of a problem for plastic surgeons and orthodontists. In this regard, the installation in this sector of implants, following ambitious bone surgery involving the sacrifice of the teeth of the medial nasal process in bilateral forms, is a protocol that could usefully be taken into account. PMID- 25127755 TI - ZnO nanoparticles induced adjuvant effect via toll-like receptors and Src signaling in Balb/c mice. AB - Our previous studies indicated that zinc oxide nanoparticles (ZnO NPs) have adjuvant properties to a known allergen ovalbumin (OVA) in Balb/c mice. Therefore, in this study, we focused on the mechanisms involved in adjuvant responses induced by ZnO NPs. The eosinophil counts in the Peyers' patches of intestine and ICAM-1, Cox2 protein expressions were enhanced in the ZnO NPs/OVA group. Following screening of toll-like receptors (TLRs), TLR 2, 4 and 6 were found to be increased. Accordingly, we found that downstream proteins of TLRs such as myeloid differentiation primary response protein-88 (MyD88), IL-1 receptor associated kinase 1 (IRAK 1), and TNFR-associated factor 6 (TRAF 6) were also found to be enhanced in the ZnO NPs/OVA-induced group. These inflammatory responses underlined the critical roles of TLRs in the inflammatory response. ZnO NPs increased the mRNA levels of inflammatory cytokine IL-1beta and protein expression of several mediators, including Cox2, PGE2, MMP-9 and finally caspase 1 in macrophages. Another pathway for adjuvant effect is Src which was found to be significantly affected by the activation of p-Lyn, p-Syk, IP3, p-PLC-gamma and cAMP. Ca(2+) influx was significantly increased as well in the ZnO NPs/OVA group. These findings demonstrated the differential role of TLRs in regulation of the ZnO NPs-induced adjuvant responses causing the inflammation. We therefore, conclude that ZnO NPs have significant adjuvant effect via following Src kinase and TLRs signaling that ascribed to inflammatory responses due to recruitment and activation of adhesion molecules and inflammatory cells. The adjuvant property of ZnO NPs may help in planning strategies for its therapeutic use. PMID- 25127756 TI - Compensatory effects of hOGG1 for hMTH1 in oxidative DNA damage caused by hydrogen peroxide. AB - OBJECTIVE: To investigate the potential compensatory effects of hOGG1 and hMTH1 in the repair of oxidative DNA damage. METHODS: The hOGG1 and hMTH1 gene knockdown human embryonic pulmonary fibroblast cell lines were established by lentivirus-mediated RNA interference. The messenger RNA (mRNA) levels of hOGG1 and hM1TH1 were analyzed by the real-time polymerase chain reaction, and 8 hydroxy-2'-deoxyguanosine (8-oxo-dG) formation was analyzed in a high-performance liquid chromatography-electrochemical detection system. RESULTS: The hOGG1 and hMTH1 knockdown cells were obtained through blasticidin selection. After transfection of hOGG1 and hMTH1 small interfering RNA, the expression levels of the mRNA of hOGG1 and hMTH1 genes were decreased by 97.2% and 96.2%, respectively. The cells then were exposed to 100 MUmol/L of hydrogen peroxide (H2O2) for 12 h to induce oxidative DNA damage. After H2O2 exposure, hMTH1 mRNA levels were increased by 25% in hOGG1 gene knockdown cells, whereas hOGG1 mRNA levels were increased by 52% in hMTH1 gene knockdown cells. Following the treatment with H2O2, the 8-oxo-dG levels in the DNA of hOGG1 gene knockdown cells were 3.1-fold higher than those in untreated HFL cells, and 1.67-fold higher than those in H2O2-treated wild-type cells. The 8-oxo-dG levels in hMTH1 gene knockdown cells were 2.3-fold higher than those in untreated human embryonic pulmonary fibroblast cells, but did not differ significantly from those in H2O2 treated wild-type cells. CONCLUSION: Our data suggested that hOGG1 could compensate for hMTH1 during oxidative DNA damage caused by H2O2, whereas hMTH1 could not compensate sufficiently for hOGG1 during the process. PMID- 25127757 TI - Insulin-like growth factor binding protein 5 (IGFBP5) mediates methamphetamine induced dopaminergic neuron apoptosis. AB - Overexposure to methamphetamine (METH), a psychoactive drug, induces a variety of adverse effects to the nervous system, including apoptosis of dopaminergic neurons. Insulin-like growth factor binding protein 5 (IGFBP5), a member of insulin-like growth factor (IGF) system, is a pro-apoptotic factor that plays important roles in neuronal apoptosis. To test the hypothesis that IGFBP5 can mediate METH-induced neuronal apoptosis, we examined IGFBP5 mRNA and protein expression changes in PC12 cells exposed to METH (3.0mM) for 24h and in the striatum of rats following 15 mg/kg * 8 intraperitoneal injections of METH at 12h interval. We also checked the effect on neuronal apoptosis after silencing IGFBP5 expression with TUNEL staining and flow cytometry; Western blot was used for detecting the expression of apoptotic markers active-caspase3 and PARP. To elucidate the mechanisms underlying IGFBP5-mediated neuronal apoptosis, we determined the release of cytochrome c (cyto c), an apoptogenic factor, from the mitochondria after METH treatment with or without IGFBP5 knockdown. Our results showed that IGFBP5 expression was increased significantly after METH exposure in PC12 cells and in the METH-treated rats' striatum. Further, METH-exposed PC12 cells exhibited higher apoptosis-positive cell number and activity of caspase3 and PARP compared with control cells, while these changes can be blocked by silencing IGFBP5 expression. In addition, a significant increase of cyto c release from mitochondria after METH exposure was observed and it was inhibited after silencing IGFBP5 expression in PC12 cells. These results indicate that IGFBP5 plays key roles in METH-induced neuronal apoptosis and may be a potential gene target for therapeutics in METH-caused neurotoxicity. PMID- 25127748 TI - Pegylated interferon plus ribavirin in HIV-infected patients with recurrent hepatitis C after liver transplantation: a prospective cohort study. AB - BACKGROUND & AIMS: The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients. METHODS: This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. RESULTS: Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p=0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. CONCLUSIONS: The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly. PMID- 25127758 TI - A human ether-a-go-go-related (hERG) ion channel atomistic model generated by long supercomputer molecular dynamics simulations and its use in predicting drug cardiotoxicity. AB - Acquired cardiac long QT syndrome (LQTS) is a frequent drug-induced toxic event that is often caused through blocking of the human ether-a-go-go-related (hERG) K(+) ion channel. This has led to the removal of several major drugs post approval and is a frequent cause of termination of clinical trials. We report here a computational atomistic model derived using long molecular dynamics that allows sensitive prediction of hERG blockage. It identified drug-mediated hERG blocking activity of a test panel of 18 compounds with high sensitivity and specificity and was experimentally validated using hERG binding assays and patch clamp electrophysiological assays. The model discriminates between potent, weak, and non-hERG blockers and is superior to previous computational methods. This computational model serves as a powerful new tool to predict hERG blocking thus rendering drug development safer and more efficient. As an example, we show that a drug that was halted recently in clinical development because of severe cardiotoxicity is a potent inhibitor of hERG in two different biological assays which could have been predicted using our new computational model. PMID- 25127759 TI - The education of UK specialised neonatal nurses: reviewing the rationale for creating a standard competency framework. AB - This paper examines the influences surrounding formal education provision for specialised neonatal nurses in the UK and presents a standardised clinical competency framework in response. National drivers for quality neonatal care define links to the numbers and ratios of specialised neonatal nurses in practice. Historical changes to professional nursing governance have led to diversity in supporting education programmes, making achievement of a standard level of clinical competence for this element of the nursing workforce difficult. In addition responsibility for funding specialised education and training has moved from central to local hospital level. Evaluating these key influences on education provision rationalised the development, by a UK professional consensus group, of a criteria based framework to be utilised by both formal education and service providers. The process identified clinical competency (in terms of unique knowledge and skills), evidence of achievement, and quality education principles. Access to specialised education relies on the availability of programmes of study and clear funding strategies. Creating a core syllabus for education provides a tool to standardise course content, commission education and audit clinical competency. In addition partnerships between healthcare and education providers become successful in achieving standard specialised education for neonatal nurses. PMID- 25127845 TI - How to evaluate appendices with borderline diameters on CT: proposal of a quick solution to overcome the limitations of the established CT criteria. AB - RATIONALE AND OBJECTIVES: To propose a useful computed tomography (CT) criterion, the diameter with compression (DWC), especially in appendices with borderline diameters. MATERIALS AND METHODS: We retrospectively collected 216 patients with visible appendices on CT after clinicopathologic confirmation of appendicitis. Each CT criterion of appendicitis was evaluated by an experienced abdominal radiologist: maximal outer diameter (MOD), DWC, mural thickness and enhancement, periappendiceal infiltration, and appendicolith. DWC is the expected diameter after deduction of the intraluminal compressible contents such as air and feces. All the CT criteria were compared in the appendicitis and nonappendicitis group. RESULTS: The areas under the receiver operating characteristic curve (AUC) of the MOD and the DWC were 0.967 and 0.973, respectively. The optimal cutoff value was 8.2 mm for the MOD and 6.6 mm for the DWC. Twenty-five of the 80 appendicitis patients (31.2%) and 62 of the 136 nonappendicitis patients (45.6%) had MODs between 5.7 mm and 9.8 mm in the overlap between the two groups. In this overlap, the AUC of the MODs declined sharply to 0.767, whereas the AUC of the DWCs remained 0.923. Use of the criterion of DWC >6.6 mm yielded a sensitivity of 84.0%, a specificity of 88.7%, and an accuracy of 87.4%. There were no other criteria with both sensitivity and specificity >80% in the range of overlap. CONCLUSIONS: The proposed CT criterion of the DWC is not affected by normal distension or periappendiceal inflammation but only by true appendicitis. Therefore, DWC can improve the diagnostic performance of appendicitis regardless of the MOD. PMID- 25127846 TI - Use of contrast-enhanced spectral mammography for intramammary cancer staging: preliminary results. AB - RATIONALE AND OBJECTIVES: To prospectively evaluate and compare the accuracy of contrast-enhanced spectral mammography (CESM) and ultrasound (US) in size measurement of breast cancer with histologic tumor sizes as gold standard. MATERIALS AND METHODS: Twenty women aged between 40-73 years (mean age, 57 +/- 10 years) with histologically proven invasive ductal/lobular carcinomas were included in the study. Agreement between imaging tumor size (CESM and US) and histopathologic tumor size was evaluated with Bland-Altman analysis. Stereotactically guided vacuum biopsy was performed in four patients after CESM. Two independent reviewers described artifacts of CESM. RESULTS: Motion artifacts did not occur in the study. CESM-specific artifacts caused by scattered radiation mostly occurred in oblique view of CESM. Background enhancement of breast tissue was seen in four patients. Mean difference of tumor sizes was 0.3 mm (6.34%) between CESM and histology and -2.2 mm (-7.59%) between US and histology. Limits of agreement ranged from -18.9 to 19.48 mm for CESM and from -17.1 to 12.7 mm with US. Especially smaller tumors with a size <23 mm were measured more precisely with CESM. Enhancement of breast tissue around microcalcifications correlated with abnormalities. CONCLUSIONS: CESM is accurate in size measurements of small breast tumors. On average CESM leads to a slight overestimation of tumor size, whereas US tends to underestimate tumor size. Assessment of the breast tissue can be limited by the scattered radiation artifact and background enhancement of breast tissue. CESM seems to be helpful in the characterization of breast tissue around microcalcifications. PMID- 25127847 TI - Simple and efficient method for region of interest value extraction from picture archiving and communication system viewer with optical character recognition software and macro program. AB - RATIONALE AND OBJECTIVES: The objectives are: 1) to introduce a simple and efficient method for extracting region of interest (ROI) values from a Picture Archiving and Communication System (PACS) viewer using optical character recognition (OCR) software and a macro program, and 2) to evaluate the accuracy of this method with a PACS workstation. MATERIALS AND METHODS: This module was designed to extract the ROI values on the images of the PACS, and created as a development tool by using open-source OCR software and an open-source macro program. The principal processes are as follows: (1) capture a region of the ROI values as a graphic file for OCR, (2) recognize the text from the captured image by OCR software, (3) perform error-correction, (4) extract the values including area, average, standard deviation, max, and min values from the text, (5) reformat the values into temporary strings with tabs, and (6) paste the temporary strings into the spreadsheet. This principal process was repeated for the number of ROIs. The accuracy of this module was evaluated on 1040 recognitions from 280 randomly selected ROIs of the magnetic resonance images. The input times of ROIs were compared between conventional manual method and this extraction module assisted input method. RESULTS: The module for extracting ROI values operated successfully using the OCR and macro programs. The values of the area, average, standard deviation, maximum, and minimum could be recognized and error-corrected with AutoHotkey-coded module. The average input times using the conventional method and the proposed module-assisted method were 34.97 seconds and 7.87 seconds, respectively. CONCLUSIONS: A simple and efficient method for ROI value extraction was developed with open-source OCR and a macro program. Accurate inputs of various numbers from ROIs can be extracted with this module. The proposed module could be applied to the next generation of PACS or existing PACS that have not yet been upgraded. PMID- 25127848 TI - Effect of light and vigorous physical activity on balance and gait of older adults. AB - This study aims to quantitatively assess the effects of vigorous and light physical activity (VPA, LPA) on static balance, gait and sit-to-stand (STS) tasks in a cohort of healthy older adults. To this end, 34 individuals of age >65 years were divided into two groups (n=17 each) who underwent 36 sessions (3*12 weeks) of PA characterized by different levels of intensity, assessed through continuous heart rate monitoring during the training session. Their balance and mobility were objectively evaluated on the basis of postural sway and time of STS measurements performed using a force platform. The main spatiotemporal parameters of gait (i.e. speed, stride and gait cycle duration, stance, swing and double support phase duration) were also acquired using a wearable inertial measurement unit. The results show that most gait parameters and STS time significantly improve in the VPA group but not in the LPA one. For the latter group a reduction only of swing phase duration was detected. PA also induced a generalized reduction of postural sway in both groups in the case of absence of visual input. These findings suggest that PA programs characterized by superior levels of intensity might be more suitable in generally improving static and dynamic daily motor tasks, while in terms of static balance acceptable results can be achieved even when only light activity is performed. PMID- 25127850 TI - Differential expression of estrogen receptor alpha in the embryonic adrenal kidney-gonadal complex of the oviparous lizard, Calotes versicolor (Daud.). AB - Estrogen signalling is critical for ovarian differentiation in reptiles with temperature-dependent sex determination (TSD). To elucidate the involvement of estrogen in this process, adrenal-kidney-gonadal (AKG) expression of estrogen receptor (ERalpha) was studied at female-producing temperature (FPT) in the developing embryos of the lizard, Calotes versicolor which exhibits a distinct pattern of TSD. The eggs of this lizard were incubated at 31.5+/-0.5 degrees C (100% FPT). The torso of embryos containing adrenal-kidney-gonadal complex (AKG) was collected during different stages of development and subjected to Western blotting and immunohistochemistry analysis. The ERalpha antibody recognized two protein bands with apparent molecular weight ~55 and ~45kDa in the total protein extracts of embryonic AKG complex of C. versicolor. The observed results suggest the occurrence of isoforms of ERalpha. The differential expression of two different protein isoforms may reveal their distinct role in cell proliferation during gonadal differentiation. This is the first report to reveal two isoforms of the ERalpha in a reptile during development. Immunohistochemical studies reveal a weak, but specific, cytoplasmic ERalpha immunostaining exclusively in the AKG during late thermo-sensitive period suggesting the responsiveness of AKG to estrogens before gonadal differentiation at FPT. Further, cytoplasmic as well as nuclear expression of ERalpha in the medulla and in oogonia of the cortex (faint activity) at gonadal differentiation stage suggests that the onset of gonadal estrogen activity coincides with sexual differentiation of gonad. Intensity and pattern of the immunoreactions of ERalpha in the medullary region at FPT suggest endogenous production of estrogen which may act in a paracrine fashion to induce neighboring cells into ovarian differentiation pathway. PMID- 25127849 TI - Bothrops jararacussu snake venom-induces a local inflammatory response in a prostanoid- and neutrophil-dependent manner. AB - Local tissue reactions provoked by Bothrops venoms are characterized by edema, hemorrhage, pain, and inflammation; however, the mechanisms of tissue damage vary depending upon the species of snake. Here, we investigated the mechanisms involved in the local inflammatory response induced by the Bothrops jararacussu venom (BjcuV). Female Swiss mice were injected with either saline, BjcuV (0.125-8 MUg/paw) or loratadine (an H1 receptor antagonist), compound 48/80 (for mast cell depletion), capsaicin (for C-fiber desensitization), infliximab (an anti-TNF alpha antibody), indomethacin (a non-specific COX inhibitor), celecoxib (a selective COX-2 inhibitor) or fucoidan (a P- and L-selectins modulator) given before BjcuV injection. Paw edema was measured by plethysmography. In addition, paw tissues were collected for the measurement of myeloperoxidase activity, TNF alpha and IL-1 levels, and COX-2 immunoexpression. The direct chemotactic effect of BjcuV and the in vitro calcium dynamic in neutrophils were also investigated. BjcuV caused an edematogenic response with increased local production of TNF alpha and IL-1beta as well as COX-2 expression. Both edema and neutrophil migration were prevented by pretreatment with indomethacin, celecoxib or fucoidan. Furthermore, BjcuV induced a direct in vitro neutrophil chemotaxis by increasing intracellular calcium. Therefore, BjcuV induces an early onset edema dependent upon prostanoid production and neutrophil migration. PMID- 25127851 TI - Advanced diffusion MRI fiber tracking in neurosurgical and neurodegenerative disorders and neuroanatomical studies: A review. AB - Diffusion MRI enabled in vivo microstructural imaging of the fiber tracts in the brain resulting in its application in a wide range of settings, including in neurological and neurosurgical disorders. Conventional approaches such as diffusion tensor imaging (DTI) have been shown to have limited applications due to the crossing fiber problem and the susceptibility of their quantitative indices to partial volume effects. To overcome these limitations, the recent focus has shifted to the advanced acquisition methods and their related analytical approaches. Advanced white matter imaging techniques provide superior qualitative data in terms of demonstration of multiple crossing fibers in their spatial orientation in a three dimensional manner in the brain. In this review paper, we discuss the advancements in diffusion MRI and introduce their roles. Using examples, we demonstrate the role of advanced diffusion MRI-based fiber tracking in neuroanatomical studies. Results from its preliminary application in the evaluation of intracranial space occupying lesions, including with respect to future directions for prognostication, are also presented. Building upon the previous DTI studies assessing white matter disease in Huntington's disease and Amyotrophic lateral sclerosis; we also discuss approaches which have led to encouraging preliminary results towards developing an imaging biomarker for these conditions. PMID- 25127852 TI - [Meningitis to Candida albicans at the adult, use of the new diagnosis methods]. AB - Candida albicans or non-albicans are a frequent source of infection but seldom displayed in cerebrospinal fluid although responsible of an important number of nosocomial meningitis. Diagnosis is difficult which often delays treatment, which in turn hinders prognostic. This clinical case shows a patient afflicted with a deadly C. albicans meningitis and allows us to focus on new diagnostic tools and advice against this infection. PMID- 25127853 TI - Intraoperative management of heart-lung interactions: "from hypothetical prediction to improved titration". AB - Extensive literature describes the suitability of dynamic parameters to predict responsiveness in fluid. However, based on heart-lung interactions, these parameters can have serious limitations, including the use of protective lung ventilation. Although the latter seems to be beneficial for healthy patients undergoing high-risk surgery, the intraoperative interpretation of dynamic parameters to predict fluid responsiveness can be hazardous. In this context, the attending physician could, alternatively, titrate the need of fluids with a small fluid challenge, which remains unaffected by low tidal volume, the presence of arrhythmia, or the presence of spontaneous ventilation. When intraoperative prediction of fluid responsiveness is required in mechanically ventilated patients, "improved" titration should be preferred to a hypothetical prediction. PMID- 25127854 TI - Auditory feedback perturbation in children with developmental speech sound disorders. AB - BACKGROUND/PURPOSE: Several studies indicate a close relation between auditory and speech motor functions in children with speech sound disorders (SSD). The aim of this study was to investigate the ability to compensate and adapt for perturbed auditory feedback in children with SSD compared to age-matched normally developing children. METHOD: 17 normally developing children aged 4.1-8.7 years (mean=5.5, SD=1.4), and 11 children with SSD aged 3.9-7.5 years (mean=5.1, SD=1.0) participated in the study. Auditory feedback was perturbed by real-time shifting the first and second formant of the vowel /e/ during the production of CVC words in a five-step paradigm (practice/familiarization; start/baseline; ramp; hold; end/release). RESULTS: At the group level, the normally developing children were better able to compensate and adapt, adjusting their formant frequencies in the direction opposite to the perturbation, while the group of children with SSD followed (amplifying) the perturbation. However, large individual differences lie underneath. Furthermore, strong correlations were found between the amount of compensation and performance on oral motor movement non-word repetition tasks. CONCLUSIONS: Results suggested that while most children with SSD can detect incongruencies in auditory feedback and can adapt their target representations, they are unable to compensate for perturbed auditory feedback. These findings suggest that impaired auditory-motor integration may play a key role in SSD. LEARNING OUTCOMES: The reader will be able to: (1) describe the potential role of auditory feedback control in developmental speech disorders (SSD); (2) identify the neural control subsystems involved in feedback based speech motor control; (3) describe the differences between compensation and adaptation for perturbed auditory feedback; (4) explain why auditory-motor integration may play a key role in SSD. PMID- 25127855 TI - The ataxia telangiectasia mutated and cyclin D3 proteins cooperate to help enforce TCRbeta and IgH allelic exclusion. AB - Coordination of V rearrangements between loci on homologous chromosomes is critical for Ig and TCR allelic exclusion. The Ataxia Telangietasia mutated (ATM) protein kinase promotes DNA repair and activates checkpoints to suppress aberrant Ig and TCR rearrangements. In response to RAG cleavage of Igkappa loci, ATM inhibits RAG expression and suppresses further Vkappa-to-Jkappa rearrangements to enforce Igkappa allelic exclusion. Because V recombination between alleles is more strictly regulated for TCRbeta and IgH loci, we evaluated the ability of ATM to restrict biallelic expression and V-to-DJ recombination of TCRbeta and IgH genes. We detected greater frequencies of lymphocytes with biallelic expression or aberrant V-to-DJ rearrangement of TCRbeta or IgH loci in mice lacking ATM. A preassembled DJbeta complex that decreases the number of TCRbeta rearrangements needed for a productive TCRbeta gene further increased frequencies of ATM deficient cells with biallelic TCRbeta expression. IgH and TCRbeta proteins drive proliferation of prolymphocytes through cyclin D3 (Ccnd3), which also inhibits VH transcription. We show that inactivation of Ccnd3 leads to increased frequencies of lymphocytes with biallelic expression of IgH or TCRbeta genes. We also show that Ccnd3 inactivation cooperates with ATM deficiency to increase the frequencies of cells with biallelic TCRbeta or IgH expression while decreasing the frequency of ATM-deficient lymphocytes with aberrant V-to-DJ recombination. Our data demonstrate that core components of the DNA damage response and cell cycle machinery cooperate to help enforce IgH and TCRbeta allelic exclusion and indicate that control of V-to-DJ rearrangements between alleles is important to maintain genomic stability. PMID- 25127856 TI - Idiotype-specific Th cells support oligoclonal expansion of anti-dsDNA B cells in mice with lupus. AB - Systemic lupus erythematosus (SLE) is marked by a Th cell-dependent B cell hyperresponsiveness, with frequent germinal center reactions and hypergammaglobulinemia. The specificity of Th cells in lupus remains unclear, but B cell Ids have been suggested. A hallmark is the presence of anti-dsDNA, mutated IgG autoantibodies with a preponderance of arginines in CDR3 of the Ig variable H chain (IgVH). B cells can present V region-derived Id peptides on their MHC class II molecules to Id-specific Th cells. We show that Id-specific Th cells support the proliferation of anti-dsDNA Id(+) B cells in mice suffering from systemic autoimmune disease with SLE-like features. Mice developed marked clonal expansions of B cells; half of the IgVH sequences were clonally related. Anti dsDNA B cells made up 40% of B cells in end-stage disease. The B cells expressed mutated IgVH with multiple arginines in CDR3. Hence, Id-driven T cell-B cell collaboration supported the production of classical anti-dsDNA Abs, recapitulating the characteristics of such Abs in SLE. The results support the concept that Id-specific Th cells may trigger the development of SLE and suggest that manipulation of the Id-specific T cell repertoire could play a role in treatment. PMID- 25127857 TI - Myeloid-specific disruption of tyrosine phosphatase Shp2 promotes alternative activation of macrophages and predisposes mice to pulmonary fibrosis. AB - The alternative activation of M2 macrophages in the lungs has been implicated as a causative agent in pulmonary fibrosis; however, the mechanisms underlying M2 polarization are poorly characterized. In this study, we investigated the role of the ubiquitously expressed Src homology domain-containing tyrosine phosphatase Shp2 in this process. Shp2 inactivation augmented IL-4-mediated M2 polarization in vitro, suggesting that Shp2 regulates macrophage skewing and prevents a bias toward the M2 phenotype. Conditional removal of Shp2 in monocytes/macrophages with lysozyme M promoter-driven Cre recombinase caused an IL-4-mediated shift toward M2 polarization. Additionally, an increase in arginase activity was detected in Shp2(?/?) mice after i.p. injection of chitin, whereas Shp2-deficient macrophages showed enhanced M2 polarization and protection against schistosome egg-induced schistosomiasis. Furthermore, mutants were more sensitive than control mice to bleomycin-induced inflammation and pulmonary fibrosis. Shp2 was associated with IL-4Ralpha and inhibited JAK1/STAT6 signaling through its phosphatase activity; loss of Shp2 promoted the association of JAK1 with IL 4Ralpha, which enhanced IL-4-mediated JAK1/STAT6 activation that resulted in M2 skewing. Taken together, these findings define a role for Shp2 in alveolar macrophages and reveal that Shp2 is required to inhibit the progression of M2 associated pulmonary fibrosis. PMID- 25127858 TI - Role of TGF-beta signaling in generation of CD39+CD73+ myeloid cells in tumors. AB - There is growing evidence that generation of adenosine from ATP, which is mediated by the CD39/CD73 enzyme pair, predetermines immunosuppressive and proangiogenic properties of myeloid cells. We have previously shown that the deletion of the TGF-beta type II receptor gene (Tgfbr2) expression in myeloid cells is associated with decreased tumor growth, suggesting protumorigenic effect of TGF-beta signaling. In this study, we tested the hypothesis that TGF-beta drives differentiation of myeloid-derived suppressor cells into protumorigenic terminally differentiated myeloid mononuclear cells (TDMMCs) characterized by high levels of cell-surface CD39/CD73 expression. We found that TDMMCs represent a major cell subpopulation expressing high levels of both CD39 and CD73 in the tumor microenvironment. In tumors isolated from mice with spontaneous tumor formation of mammary gland and conditional deletion of the type II TGF-beta receptor in mammary epithelium, an increased level of TGF-beta protein was associated with further increase in number of CD39(+)CD73(+) TDMMCs compared with MMTV-PyMT/TGFbetaRII(WT) control tumors with intact TGF-beta signaling. Using genetic and pharmacological approaches, we demonstrated that the TGF-beta signaling mediates maturation of myeloid-derived suppressor cells into TDMMCs with high levels of cell surface CD39/CD73 expression and adenosine-generating capacity. Disruption of TGF-beta signaling in myeloid cells resulted in decreased accumulation of TDMMCs, expressing CD39 and CD73, and was accompanied by increased infiltration of T lymphocytes, reduced density of blood vessels, and diminished progression of both Lewis lung carcinoma and spontaneous mammary carcinomas. We propose that TGF-beta signaling can directly induce the generation of CD39(+)CD73(+) TDMMCs, thus contributing to the immunosuppressive, proangiogenic, and tumor-promoting effects of this pleiotropic effector in the tumor microenvironment. PMID- 25127860 TI - Differences in the transduction of canonical Wnt signals demarcate effector and memory CD8 T cells with distinct recall proliferation capacity. AB - Protection against reinfection is mediated by Ag-specific memory CD8 T cells, which display stem cell-like function. Because canonical Wnt (Wingless/Int1) signals critically regulate renewal versus differentiation of adult stem cells, we evaluated Wnt signal transduction in CD8 T cells during an immune response to acute infection with lymphocytic choriomeningitis virus. Whereas naive CD8 T cells efficiently transduced Wnt signals, at the peak of the primary response to infection only a fraction of effector T cells retained signal transduction and the majority displayed strongly reduced Wnt activity. Reduced Wnt signaling was in part due to the downregulation of Tcf-1, one of the nuclear effectors of the pathway, and coincided with progress toward terminal differentiation. However, the correlation between low and high Wnt levels with short-lived and memory precursor effector cells, respectively, was incomplete. Adoptive transfer studies showed that low and high Wnt signaling did not influence cell survival but that Wnt high effectors yielded memory cells with enhanced proliferative potential and stronger protective capacity. Likewise, following adoptive transfer and rechallenge, memory cells with high Wnt levels displayed increased recall expansion, compared with memory cells with low Wnt signaling, which were preferentially effector-like memory cells, including tissue-resident memory cells. Thus, canonical Wnt signaling identifies CD8 T cells with enhanced proliferative potential in part independent of commonly used cell surface markers to discriminate effector and memory T cell subpopulations. Interventions that maintain Wnt signaling may thus improve the formation of functional CD8 T cell memory during vaccination. PMID- 25127859 TI - Release of active TGF-beta1 from the latent TGF-beta1/GARP complex on T regulatory cells is mediated by integrin beta8. AB - Activated T regulatory cells (Tregs) express latent TGF-beta1 on their cell surface bound to GARP. Although integrins have been implicated in mediating the release of active TGF-beta1 from the complex of latent TGF-beta1 and latent TGF beta1 binding protein, their role in processing latent TGF-beta1 from the latent TGF-beta1/GARP complex is unclear. Mouse CD4(+)Foxp3(+) Treg, but not CD4(+)Foxp3(-) T cells, expressed integrin beta8 (Itgb8) as detected by quantitative RT-PCR. Itgb8 expression was a marker of thymically derived (t)Treg, because it could not be detected on Foxp3(+)Helios(-) Tregs or on Foxp3(+) T cells induced in vitro. Tregs from Itgb8 conditional knockouts exhibited normal suppressor function in vitro and in vivo in a model of colitis but failed to provide TGF-beta1 to drive Th17 or induced Treg differentiation in vitro. In addition, Itgb8 knockout Tregs expressed higher levels of latent TGF-beta1 on their cell surface consistent with defective processing. Thus, integrin alphavbeta8 is a marker of tTregs and functions in a cell intrinsic manner in mediating the processing of latent TGF-beta1 from the latent TGF-beta1/GARP complex on the surface of tTregs. PMID- 25127861 TI - The N-terminal domain of NLRC5 confers transcriptional activity for MHC class I and II gene expression. AB - Ag presentation to CD4(+) and CD8(+) T cells depends on MHC class II and MHC class I molecules, respectively. One important regulatory factor of this process is the transcriptional regulation of MHC gene expression. It is well established that MHC class II transcription relies on the NLR protein CIITA. Recently, another NLR protein, NLRC5, was shown to drive MHC class I expression. The molecular mechanisms of the function of NLRC5 however remain largely elusive. In this study, we present a detailed functional study of the domains of NLRC5 revealing that the N-terminal domain of human NLRC5 has intrinsic transcriptional activity. Domain swapping experiments between NLRC5 and CIITA showed that this domain contributes to MHC class I and MHC class II gene expression with a bias for activation of MHC class I promoters. Delivery of this construct by adeno associated viral vectors upregulated MHC class I and MHC class II expression in human cells and enhanced lysis of melanoma cells by CD8(+) cytotoxic T cells in vitro. Taken together, this work provides novel insight into the function of NLRC5 and CIITA in MHC gene regulation. PMID- 25127862 TI - The expression of sphingosine-1 phosphate receptor-1 in chronic lymphocytic leukemia cells is impaired by tumor microenvironmental signals and enhanced by piceatannol and R406. AB - Chronic lymphocytic leukemia (CLL) is characterized by the progressive accumulation of clonal B lymphocytes. Proliferation occurs in lymphoid tissues upon interaction of leukemic cells with a supportive microenvironment. Therefore, the mobilization of tissue-resident CLL cells into the circulation is a useful therapeutic strategy to minimize the reservoir of tumor cells within survival niches. Because the exit of normal lymphocytes from lymphoid tissues depends on the presence of sphingosine-1 phosphate (S1P) and the regulated expression of S1P receptor-1 (S1PR1), we investigated whether the expression and function of S1PR1 can be modulated by key microenvironment signals. We found that activation of CLL cells with CXCL12, fibroblast CD40L(+), BCR cross-linking, or autologous nurse like cells reduces their S1PR1 expression and the migratory response toward S1P. Moreover, we found that S1PR1 expression was reduced in the proliferative/activated subset of leukemic cells compared with the quiescent subset from the same patient. Similarly, bone marrow-resident CLL cells expressing high levels of the activation marker CD38 showed a lower expression of S1PR1 compared with CD38(low) counterparts. Finally, given that treatment with BCR-associated kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1 might modulate the egress of the leukemic clone from lymphoid tissues. PMID- 25127863 TI - Concomitant TLR/RLH signaling of radioresistant and radiosensitive cells is essential for protection against vesicular stomatitis virus infection. AB - Several studies indicated that TLR as well as retinoic acid-inducible gene I-like helicase (RLH) signaling contribute to vesicular stomatitis virus (VSV)-mediated triggering of type I IFN (IFN-I) responses. Nevertheless, TLR-deficient MyD88(-/ )Trif(-/-) mice and RLH-deficient caspase activation and recruitment domain adaptor inducing IFN-beta (Cardif)(-/-) mice showed only marginally enhanced susceptibility to lethal VSV i.v. infection. Therefore, we addressed whether concomitant TLR and RLH signaling, or some other additional mechanism, played a role. To this end, we generated MyD88(-/-)Trif(-/-)Cardif(-/-) (MyTrCa(-/-)) mice that succumbed to low-dose i.v. VSV infection with similar kinetics as IFN-I receptor-deficient mice. Three independent approaches (i.e., analysis of IFN alpha/beta serum levels, experiments with IFN-beta reporter mice, and investigation of local IFN-stimulated gene induction) revealed that MyTrCa(-/-) mice did not mount IFN-I responses following VSV infection. Of note, treatment with rIFN-alpha protected the animals, qualifying MyTrCa(-/-) mice as a model to study the contribution of different immune cell subsets to the production of antiviral IFN-I. Upon adoptive transfer of wild-type plasmacytoid dendritic cells and subsequent VSV infection, MyTrCa(-/-) mice displayed significantly reduced viral loads in peripheral organs and showed prolonged survival. On the contrary, adoptive transfer of wild-type myeloid dendritic cells did not have such effects. Analysis of bone marrow chimeric mice revealed that TLR and RLH signaling of radioresistant and radiosensitive cells was required for efficient protection. Thus, upon VSV infection, plasmacytoid dendritic cell-derived IFN-I primarily protects peripheral organs, whereas concomitant TLR and RLH signaling of radioresistant stroma cells as well as of radiosensitive immune cells is needed to effectively protect against lethal disease. PMID- 25127864 TI - Dopamine inhibits the effector functions of activated NK cells via the upregulation of the D5 receptor. AB - Several lines of evidence indicate that dopamine (DA) plays a key role in the cross-talk between the nervous and immune systems. In this study, we disclose a novel immune-regulatory role for DA: inhibition of effector functions of activated NK lymphocytes via the selective upregulation of the D5 dopaminergic receptor in response to prolonged cell stimulation with rIL-2. Indeed, engagement of this D1-like inhibitory receptor following binding with DA suppresses NK cell proliferation and synthesis of IFN-gamma. The inhibition of IFN-gamma production occurs through blocking the repressor activity of the p50/c-REL dimer of the NF kappaB complex. Indeed, the stimulation of the D5 receptor on rIL-2-activated NK cells inhibits the binding of p50 to the microRNA 29a promoter, thus inducing a de novo synthesis of this miRNA. In turn, the increased levels of microRNA 29a were inversely correlated with the ability of NK cells to produce IFN-gamma. Taken together, our findings demonstrated that DA switches off activated NK cells, thus representing a checkpoint exerted by the nervous system to control the reactivity of these innate immune effectors in response to activation stimuli and to avoid the establishment of chronic and pathologic inflammatory processes. PMID- 25127865 TI - The late endosomal transporter CD222 directs the spatial distribution and activity of Lck. AB - The spatial and temporal organization of T cell signaling molecules is increasingly accepted as a crucial step in controlling T cell activation. CD222, also known as the cation-independent mannose 6-phosphate/insulin-like growth factor 2 receptor, is the central component of endosomal transport pathways. In this study, we show that CD222 is a key regulator of the early T cell signaling cascade. Knockdown of CD222 hampers the effective progression of TCR-induced signaling and subsequent effector functions, which can be rescued via reconstitution of CD222 expression. We decipher that Lck is retained in the cytosol of CD222-deficient cells, which obstructs the recruitment of Lck to CD45 at the cell surface, resulting in an abundant inhibitory phosphorylation signature on Lck at the steady state. Hence, CD222 specifically controls the balance between active and inactive Lck in resting T cells, which guarantees operative T cell effector functions. PMID- 25127867 TI - Sodium dodecyl sulfate polyacrylamide gel electrophoresis for direct quantitation of protein adsorption. AB - A simple method, sodium dodecyl sulfate polyacrylamide gel electrophoresis coupled with direct protein adsorption analysis (SDS-PAGE/DPA), is presented here for the quantitation of adsorption-caused protein loss. No complicated steps and expensive equipment are involved, and this method is capable of measuring proteins adsorbed on sample vials at extremely low concentrations (in pg/MUl). We used this method to characterize the effects of concentration, time, and volume on adsorption. We also applied this method to discover differential sample loss in protein mixtures and its utility in developing preventive strategies of adsorption. PMID- 25127868 TI - Synthesis and evaluation of novel alkannin and shikonin oxime derivatives as potent antitumor agents. AB - A set of forty alkannin and shikonin oxime derivatives were firstly designed and synthesized. Their cytotoxicities against three kinds of tumor cells and a normal cell line were tested and compared with alkannin and shikonin. The cell-based investigation demonstrated that some oxime derivatives were more or comparatively effective to the lead compounds, especially their selective and excellent antitumor activities towards K562 cells with no toxicity in normal cells. We may conclude that oximate modification to the mother nucleus of alkannin and shikonin is an available approach to acquire potent antitumor agents. PMID- 25127866 TI - D-beta-hydroxybutyrate extends lifespan in C. elegans. AB - The ketone body beta-hydroxybutyrate (betaHB) is a histone deacetylase (HDAC) inhibitor and has been shown to be protective in many disease models, but its effects on aging are not well studied. Therefore we determined the effect of betaHB supplementation on the lifespan ofC. elegans nematodes. betaHB supplementation extended mean lifespan by approximately 20%. RNAi knockdown of HDACs hda-2 or hda-3 also increased lifespan and further prevented betaHB mediated lifespan extension. betaHB-mediated lifespan extension required the DAF 16/FOXO and SKN-1/Nrf longevity pathways, the sirtuin SIR-2.1, and the AMP kinase subunit AAK-2. betaHB did not extend lifespan in a genetic model of dietary restriction indicating that betaHB is likely functioning through a similar mechanism. betaHB addition also upregulated BetaHB dehydrogenase activity and increased oxygen consumption in the worms. RNAi knockdown of F55E10.6, a short chain dehydrogenase and SKN-1 target gene, prevented the increased lifespan and betaHB dehydrogenase activity induced by betaHB addition, suggesting that F55E10.6 functions as an inducible betaHB dehydrogenase. Furthermore, betaHB supplementation increased worm thermotolerance and partially prevented glucose toxicity. It also delayed Alzheimer's amyloid-beta toxicity and decreased Parkinson's alpha-synuclein aggregation. The results indicate that D-betaHB extends lifespan through inhibiting HDACs and through the activation of conserved stress response pathways. PMID- 25127869 TI - Development of potential selective and reversible pyrazoline based MAO-B inhibitors as MAO-B PET tracer precursors and reference substances for the early detection of Alzheimer's disease. AB - Since high MAO-B levels are present in early stages of AD, the MAO-B system can be designated as an appropriate and prospective tracer target of molecular imaging biomarkers for the detection of early AD. According to the preceding investigations of Mishra et al. the aim of this work was the development of a compound library of selective and reversible MAO-B inhibitors by performing bioisosteric modifications of the core structure of 3-(anthracen-9-yl)-5-phenyl 4,5-dihydro-1H-pyrazoles. In conclusion, 13 new pyrazoline based derivatives have been prepared, which will serve as precursor substances for future radiolabeling as well as reference compounds for the investigation of increased MAO-B levels in AD. PMID- 25127870 TI - Submonomer synthesis of azapeptide ligands of the Insulin Receptor Tyrosine Kinase domain. AB - Azapeptide ligands of the Insulin Receptor Tyrosine Kinase (IRTK) were developed by solid-phase submonomer azapeptide synthesis in sufficient isolated yields (36 55%) and purities >95% for structure-activity relationship studies. The azapeptides adopted folded geometries with some proportion of random coil according to CD and NMR spectroscopy. In vitro phosphorylation of the IRTK domain in the presence of azapeptides produced a lead inhibitor, Ac-DIazaYET-NH2 (~50% at 400 MUM) whereas the [aza-DOPA(3)] and [aza-Glu(4)] analogs were found to stimulate IRTK phosphorylations. Thus, azapeptide ligands of the IRTK provide important modulatory activity of this important class of enzymes for anti-cancer and related applications in drug discovery. PMID- 25127871 TI - Synthesis and insecticidal activity of new deoxypodophyllotoxin derivatives modified in the D-ring. AB - In continuation of our program aimed at the discovery of new natural-product based insecticidal agents, twenty-six deoxypodophyllotoxin derivatives modified in the D-ring were synthesized and evaluated as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at 1 mg/mL. The configuration of three compounds 3, 4, and IIIi was unambiguously determined by single-crystal X-ray diffraction. It demonstrated that aminolysis of deoxypodophyllotoxin in the presence of pyrrolidine and piperidine could result in complete inversion of the configuration of the carbonyl group at its C 2 position. Five compounds IIa, IIi-k, and IIIh showed the equal or higher insecticidal activity than toosendanin. Especially IIj displayed the most potent insecticidal activity with the final mortality rate of 65.5%. PMID- 25127872 TI - Cryopreservation of hepatocyte (HepG2) cell monolayers: impact of trehalose. AB - A simple method to cryogenically preserve hepatocyte monolayers is currently not available but such a technique would facilitate numerous applications in the field of biomedical engineering, cell line development, and drug screening. We investigated the effect of trehalose and dimethyl sulfoxide (Me2SO) in cryopreservation of human hepatocellular carcinoma (HepG2) cells in suspension and monolayer formats. HepG2 cell monolayers were incubated for 24h at varying concentrations of trehalose (50-150 mM) prior to cryopreservation to identify the optimum concentration for such preincubation. When trehalose alone was used as the cryoprotective agent (CPA), cells in monolayer format did not survive freezing while cells in suspension demonstrated 14% viability 24h after thawing. Only 6-13% of cells in monolayers survived freezing in cell culture medium supplemented with 10% Me2SO, but 42% of cells were recovered successfully if monolayers were preincubated with 100 mM trehalose prior to freezing in the Me2SO supplemented medium. Interestingly, for cells frozen in suspension in presence of 10% Me2SO, metabolic activity immediately following thawing did not change appreciably compared to unfrozen control cells. Finally, Raman spectroscopy techniques were employed to evaluate ice crystallization in the presence and absence of trehalose in freezing solutions without cells because crystallization may alter the extent of injury observed in cell monolayers. We speculate that biomimetic approaches of using protective sugars to preserve cells in monolayer format will facilitate the development of techniques for long-term preservation of human tissues and organs in the future. PMID- 25127873 TI - Influence of hydroxyapatite nanoparticles on the viscosity of dimethyl sulfoxide H2O-NaCl and glycerol-H2O-NaCl ternary systems at subzero temperatures. AB - The viscosity, at subzero temperatures, of ternary solutions commonly used in cryopreservation is tremendously important for understanding ice formation and molecular diffusion in biopreservation. However, this information is scarce in the literature. In addition, to the best of our knowledge, the effect of nanoparticles on the viscosity of these solutions has not previously been reported. The objectives of this study were thus: (i) to systematically measure the subzero viscosity of two such systems, dimethyl sulfoxide (Me2SO)-H2O-NaCl and glycerol-H2O-NaCl; (ii) to explore the effect of hydroxyapatite (HA) nanoparticles on the viscosity; and (iii) to provide models that precisely predict viscosity at multiple concentrations of cryoprotective agent (CPA) in saline solutions at subzero temperatures. Our experiments were performed in two parts. We first measured the viscosity at multiple CPA concentrations [0.3-0.75 (w/w)] in saline solution with and without nanoparticles at subzero temperatures (0 to -30 degrees C). The data exhibited a good fit to the Williams-Landel-Ferry (WLF) equation. We then measured the viscosity of residual unfrozen ternary solutions with and without nanoparticles during equilibrium freezing. HA nanoparticles made the solution more viscous, suggesting applications for these nanoparticles in preventing cell dehydration, ice nucleation, and ice growth during freezing and thawing in cryopreservation. PMID- 25127874 TI - The effects of cryopreservation on cells isolated from adipose, bone marrow and dental pulp tissues. AB - The effects of cryopreservation on mesenchymal stem cell (MSC) phenotype are not well documented; however this process is of increasing importance for regenerative therapies. This study examined the effect of cryopreservation (10% dimethyl-sulfoxide) on the morphology, viability, gene-expression and relative proportion of MSC surface-markers on cells derived from rat adipose, bone marrow and dental pulp. Cryopreservation significantly reduced the number of viable cells in bone marrow and dental pulp cell populations but had no observable effect on adipose cells. Flow cytometry analysis demonstrated significant increases in the relative expression of MSC surface-markers, CD90 and CD29/CD90 following cryopreservation. sqRT-PCR analysis of MSC gene-expression demonstrated increases in pluripotent markers for adipose and dental pulp, together with significant tissue-specific increases in CD44, CD73-CD105 following cryopreservation. Cells isolated from different tissue sources did not respond equally to cryopreservation with adipose tissue representing a more robust source of MSCs. PMID- 25127875 TI - Cytotoxic T lymphocytes block tumor growth both by lytic activity and IFNgamma dependent cell-cycle arrest. AB - To understand global effector mechanisms of CTL therapy, we performed microarray gene expression analysis in a murine model using pmel-1 T-cell receptor (TCR) transgenic T cells as effectors and B16 melanoma cells as targets. In addition to upregulation of genes related to antigen presentation and the MHC class I pathway, and cytotoxic effector molecules, cell-cycle-promoting genes were downregulated in the tumor on days 3 and 5 after CTL transfer. To investigate the impact of CTL therapy on the cell cycle of tumor cells in situ, we generated B16 cells expressing a fluorescent ubiquitination-based cell-cycle indicator (B16 fucci) and performed CTL therapy in mice bearing B16-fucci tumors. Three days after CTL transfer, we observed diffuse infiltration of CTLs into the tumor with a large number of tumor cells arrested at the G1 phase of the cell cycle, and the presence of spotty apoptotic or necrotic areas. Thus, tumor growth suppression was largely dependent on G1 cell-cycle arrest rather than killing by CTLs. Neutralizing antibody to IFNgamma prevented both tumor growth inhibition and G1 arrest. The mechanism of G1 arrest involved the downregulation of S-phase kinase associated protein 2 (Skp2) and the accumulation of its target cyclin-dependent kinase inhibitor p27 in the B16-fucci tumor cells. Because tumor-infiltrating CTLs are far fewer in number than the tumor cells, we propose that CTLs predominantly regulate tumor growth via IFNgamma-mediated profound cytostatic effects rather than via cytotoxicity. This dominance of G1 arrest over other mechanisms may be widespread but not universal because IFNgamma sensitivity varied among tumors. PMID- 25127876 TI - Combined submandibular gland flap and sternocleidomastoid musculocutaneous flap for postoperative reconstruction in older aged patients with oral cavity and oropharyngeal cancers. AB - BACKGROUND: The growth of aging populations in an increasing number of countries has led to a concomitant increase in the incidence of chronic diseases. Accordingly, the proportion of older aged patients with oral cavity and oropharyngeal cancers and comorbidities has also increased. Thus, improvements must be made in the tolerance and safety of surgical procedures for these patients with complex medical conditions. In this study, we investigated combined submandibular gland flap and sternocleidomastoid musculocutaneous flap for postoperative reconstruction in older aged patients with oral cavity and oropharyngeal cancers in terms of surgical methods, safety, and clinical outcome. METHODS: Between January 2011 and May 2012, 8 patients over the age of 65 years (7 men, 1 woman; aged 66 to 75 years (median, 69.6)) with oral cavity and oropharyngeal cancers underwent combined submandibular gland and sternocleidomastoid myocutaneous flaps for postoperative reconstruction at Ganzhou Tumor Hospital. All eight patients had comorbid cardiovascular, cerebrovascular, or chronic respiratory disease or diabetes. Clinical outcomes, complications, and tolerance to surgical treatment were observed. RESULTS: Surgical treatment was successful in all eight patients. All submandibular gland flaps survived with well-mucosalized surfaces and with no complications. During the postoperative follow-up period of 12 to 28 months, no patient developed local recurrence or distant metastasis, and all had good recovery of function and local contour. CONCLUSIONS: This combined reconstruction technique enables appropriate restoration of oral function, facial aesthetics and improved quality of life. Further, this technique has several advantages: it is easier to perform, reduces operation time and surgical risk, causes less surgical injury, and has minor impact on contour. The technique provides a new and safe reconstruction option for older aged patients with oral cavity and oropharyngeal cancers. PMID- 25127877 TI - Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex. AB - The mammalian circadian clock is driven by a transcriptional-translational feedback loop, which produces robust 24-hr rhythms. Proper oscillation of the clock depends on the complex formation and periodic turnover of the Period and Cryptochrome proteins, which together inhibit their own transcriptional activator complex, CLOCK-BMAL1. We determined the crystal structure of the CRY-binding domain (CBD) of PER2 in complex with CRY2 at 2.8 A resolution. PER2-CBD adopts a highly extended conformation, embracing CRY2 with a sinuous binding mode. Its N terminal end tucks into CRY adjacent to a large pocket critical for CLOCK-BMAL1 binding, while its C-terminal half flanks the CRY2 C-terminal helix and sterically hinders the recognition of CRY2 by the FBXL3 ubiquitin ligase. Unexpectedly, a strictly conserved intermolecular zinc finger, whose integrity is important for clock rhythmicity, further stabilizes the complex. Our structure guided analyses show that these interspersed CRY-interacting regions represent multiple functional modules of PERs at the CRY-binding interface. PMID- 25127879 TI - Management of adrenal incidentaloma. AB - Improvements in medical imaging have resulted in the incidental discovery of many silent and unrecognized adrenal tumors. The term "adrenal incidentaloma" (AI) is applied to any adrenal mass>=1cm in its longest axis that is discovered incidentally during abdominal imaging that was not performed to specifically evaluate adrenal pathology. These incidentalomas may be either secretory or non secretory, benign or malignant. Distinctive characteristics of these lesions must be determined by the clinician to determine appropriate management. Such distinctions are based on laboratory findings and imaging, principally CT with and without contrast injection. Investigations must be carefully chosen to avoid ordering unnecessary and expensive tests for too many patients while, at the same time, avoiding the risk of failing to diagnose a secreting malignant or tumor. These examinations will determine patient care: surgery or surveillance. When simple surveillance is chosen, specific criteria must be met with regard to diagnostic modalities (clinical, imaging, laboratory testing) and its duration. PMID- 25127878 TI - Effect of a qigong intervention program on telomerase activity and psychological stress in abused Chinese women: a randomized, wait-list controlled trial. AB - BACKGROUND: Abused women, who suffer from chronic psychological stress, have been shown to have shorter telomeres than never abused women. Telomere shortening is associated with increased risk of cell death, and it is believed that adopting health-promoting behaviors can help to increase the activity of telomerase, an enzyme that counters telomere shortening. Qigong is an ancient Chinese mind-body integration, health-oriented practice designed to enhance the function of qi, an energy that sustains well-being. Therefore, an assessor-blind, randomized, wait list controlled trial was developed to evaluate the effect of a qigong intervention on telomerase activity (primary objective) and proinflammatory cytokines, perceived stress, perceived coping, and depressive symptoms (secondary objectives) in abused Chinese women. METHODS/DESIGN: A total of 240 Chinese women, aged >= 18 years, who have been abused by an intimate partner within the past three years will be recruited from a community setting in Hong Kong and randomized to receive either a qigong intervention or wait-list control condition as follows: the qigong intervention will comprise (i) a 2-hour group qigong training session twice a week for 6 weeks, (ii) a 1-hour follow-up group qigong exercise session once a week for 4 months, and (iii) a 30-minute self-practice qigong exercise session once a day for 5.5 months. The wait-list control group will receive qigong training after the intervention group completes the program. Upon completion of the qigong intervention program, it is expected that abused Chinese women in the intervention group will have higher levels of telomerase activity and perceived coping and lower levels of proinflammatory cytokines, perceived stress, and depressive symptoms than will abused Chinese women in the wait-list control group. DISCUSSION: This study will provide information about the effect of qigong exercise on telomerase activity and chronic psychological stress in abused Chinese women. The findings will inform the design of interventions to relieve the effects of IPV-related psychological stress on health. Also, the concept that health-promoting behaviors could slow down cellular aging might even motivate abused women to change their lifestyles. TRIAL REGISTRATION: Current Controlled Trials NCT02060123. Registered February 6, 2014. PMID- 25127880 TI - An inevitable wave of prescription drug monitoring programs in the context of prescription opioids: pros, cons and tensions. AB - BACKGROUND: In an effort to control non-medical use and/or medical abuse of prescription drugs, particularly prescription opioids, electronic prescription drug monitoring programs (PDMP) have been introduced in North-American countries, Australia and some parts of Europe. Paradoxically, there are simultaneous pressures to increase opioid prescribing for the benefit of individual patients and to reduce it for the sake of public health, and this pressure warrants a delicate balance of appropriate therapeutic uses of these drugs with the risk of developing dependence. This article discusses pros and cons of PDMP in reducing diversion of prescription opioids, without hampering access to those medications for those with genuine needs, and highlights tensions around PDMP implementation. DISCUSSION: PDMPs may help alleviate diversion, over-prescription and fraudulent prescribing/dispensing; prompt drug treatment referrals; avoid awkward drug urine test; and inform spatial changes in prescribing practices and help designing tailored interventions. Fear of legal retribution, privacy and data security, potential confusion about addiction and pseudo-addiction, and potential undue pressure of detecting misuse/diversion - are the major problems. There are tensions about unintended consequence of excessive regulatory enforcements, corresponding collateral damages particularly about inadequate prescribing for patients with genuine needs, and mandatory consultation requirements of PDMP. SUMMARY: In this era of information technology PDMP is likely to flourish and remain with us for a long time. A clear standard of practice against which physicians' care will be judged may expedite the utilisation of PDMP. In addition, adequate training on addiction and pain management along with public awareness, point-of-supply data entry from pharmacy, point-of-care real-time access to data, increasing access to addiction treatment and appropriate regulatory enforcement preferably through healthcare administration, together, may help remove barriers to PDMP use. PMID- 25127881 TI - Palmoplantar pustules and osteoarticular pain in a 42-year-old woman. AB - Key teaching points * Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is characterized by distinctive osteoarticular manifestations and a spectrum of neutrophilic dermatoses. * The most common dermatologic manifestations include palmoplantar pustulosis, acne conglobata, and acne fulminans. * SAPHO syndrome should be considered in patients presenting osteoarticular pain, particularly involving the anterior chest wall and/or spine, and neutrophilic skin lesions. PMID- 25127883 TI - Chronic pancreatitis of the pancreatic remnant is an independent risk factor for pancreatic fistula after distal pancreatectomy. AB - BACKGROUND: There is an ongoing debate about the best closure technique after distal pancreatectomy (DP). The aim of the closure is to prevent the formation of a clinically relevant post-operative pancreatic fistula (POPF). Stapler technique seems to be equal compared with hand-sewn closure of the remnant. For both techniques, a fistula rate of approximately 30% has been reported. METHODS: We retrospectively analyzed our DPs between 01/2000 and 12/2010. In all cases, the pancreatic duct was over sewn with a separately stitched ligation of the pancreatic duct (5*0 PDS) followed by a single-stitched hand-sewn closure of the residual pancreatic gland. The POPF was classified according to the criteria of the International Study Group for Pancreatic Fistula (ISGPF). Univariate and multivariate analyses of potential risk factors for the formation of POPF were performed. Indications for operations included cystic tumors (n = 53), neuroendocrine tumors (n = 27), adenocarcinoma (n = 22), chronic pancreatitis (n = 9), metastasis (n = 6), and others (n = 7). RESULTS: During the period, we performed 124 DPs (? = 74, ? = 50). The mean age was 57.5 years (18-82). The POPF rates according to the ISGPF criteria were: no fistula, 54.8% (n = 68); grade A, 24.2% (n = 30); grade B, 19.3% (n = 24); and grade C, 1.7% (n = 2). Therefore, in 21.0% (n = 26) of the cases, a clinically relevant pancreatic fistula occurred. The mean postoperative stay was significantly higher after grade B/C fistula (26.3 days) compared with no fistula/grade A fistula (13.7 days) (p < 0.05). The uni- and multivariate analyses showed chronic pancreatitis of the pancreatic remnant to be an independent risk factor for the development of POPF (p = 0.004 OR 7.09). CONCLUSION: By using a standardized hand-sewn closure technique of the pancreatic remnant after DP with separately stitched ligation of the pancreatic duct, a comparably low fistula rate can be achieved. Signs of chronic pancreatitis of the pancreatic remnant may represent a risk factor for the development of a pancreatic fistula after DP and therefore an anastomosis of the remnant to the intestine should be considered. PMID- 25127884 TI - Two transaldolase isogenes from Moniliella megachiliensis behave in a different way depending on the stress class. AB - We cloned and sequenced two transaldolase genes from Moniliella megachiliensis, a microorganism known to produce a significant amount of erythritol under hyper osmotic stress. The amino acid sequences encoded by these two genes (MmTAL1, MmTAL2) showed 72% homology to each other. An AP-1 (ap response element) associated with oxidative stress was found in the promoter region of MmTAL1, while four STREs (stress response element) associated with osmotic stress were found in the promoter region of MmTAL2. In early-stage cultivation (up to 2 h), MmTAL1 was specifically expressed in response to oxidative stress generated by the presence of 0.15 mM menadione; expression level 3-fold higher than before stress loading. MmTAL2 was expressed in response to osmotic stress caused by 1.2 M NaCl; expression level was 21-fold higher than stress-free control. Erythritol accumulated intracellularly under osmotic and oxidative stress, approximately 30 fold and 35-fold, respectively. We therefore concluded that M. megachiliensis selectively uses two isogenes and produces erythritol during early-stage response to stress, depending on the type of environmental stress. PMID- 25127882 TI - High frequency of kdr L1014F is associated with pyrethroid resistance in Anopheles coluzzii in Sudan savannah of northern Nigeria. AB - BACKGROUND: Malaria burden is high in Nigeria, yet information on the major mosquito vectors is lacking especially in the Sudan savannah region of the country. In order to facilitate the design of future insecticide-based control interventions in the region, this study has established the resistance profile of An. gambiae s.l. populations in two northern Nigeria locations and assessed the contribution of target site resistance mutations. METHODS: Larval collection was conducted in two localities in Sudan savannah (Bunkure and Auyo) of northern Nigeria between 2009 and 2011, from which resulting adult, female mosquitoes were used for insecticides bioassays with deltamethrin, lambda-cyhalothrin, DDT and malathion. The mosquitoes were identified to species level and molecular forms and then genotyped for the presence of L1014F-kdr, L1014S-kdr and ace-1R mutations. RESULTS: WHO bioassays revealed that An. gambiae s.l. from both localities were highly resistant to lambda-cyhalothrin and DDT, but only moderately resistant to deltamethrin. Full susceptibility was observed to malathion. An. gambiae, M form (now An. coluzzii), was predominant over An. arabiensis in Auyo and was more resistant to lambda-cyhalothrin than An. arabiensis. No 'S' form (An. gambiae s.s.) was detected. A high frequency of 1014 F mutation (80.1%) was found in An. coluzzii in contrast to An. arabiensis (13.5%). The presence of the 1014 F kdr allele was significantly associated with resistance to lambda-cyhalothrin in An. coluzzii (OR = 9.85; P < 0.001) but not in An. arabiensis. The L1014S-kdr mutation was detected in a single An. arabiensis mosquito while no ace-1R mutation was found in any of the mosquitoes analysed. CONCLUSIONS: The predominance of An. coluzzii and its resistance profile to main insecticides described in this study can guide the implementation of appropriate vector control interventions in this region of Nigeria where such information was previously lacking. PMID- 25127885 TI - Does vitamin A supplementation protect schoolchildren from acquiring soil transmitted helminthiasis? A randomized controlled trial. AB - BACKGROUND: Despite the intensive global efforts to control intestinal parasitic infections, the prevalence of soil-transmitted helminth (STH) infections is still very high in many developing countries particularly among children in rural areas. METHODS: A randomized, double-blind, placebo-controlled trial was conducted on 250 Aboriginal schoolchildren in Malaysia to investigate the effects of a single high-dose of vitamin A supplementation (200,000 IU) on STH reinfection. The effect of the supplement was assessed at 3 and 6 months after receiving interventions; after a complete 3-day deworming course of 400 mg/daily of albendazole tablets. RESULTS: Almost all children (98.6%) were infected with at least one STH species. The overall prevalence of ascariasis, trichuriasis and hookworm infection was 67.8%, 95.5% and 13.4%, respectively. Reinfection rates of Ascaris, Trichuris and hookworm were high; at 6 months, assessment reached 80% of the prevalence reported before treatment. There were no significant differences in the reinfection rates and intensities of STH between vitamin A supplemented children and those who received placebo at 3 and 6 months (p > 0.05). CONCLUSIONS: Vitamin A supplementation showed no protective effect against STH reinfection and this could be due to the high endemicity of STH in this community. Long-term interventions to reduce poverty will help significantly in reducing this continuing problem and there is no doubt that reducing intestinal parasitic infection would have a positive impact on the health, nutrition and education of these children. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov as NCT00936091. PMID- 25127886 TI - Estimates of adherence to treatment of vivax malaria. AB - BACKGROUND: The relation between therapeutic failure and non-adherence to treatment of malaria has been clearly established. Several measures have been used to estimate adherence to Plasmodium vivax therapy, but few protocols have been validated to ensure reliability of the estimates of adherence. The objective of this study was to validate a five-item-reported-questionnaire derived from original Morisky four-item scale to estimate adherence to P. vivax malaria therapy. METHODS: A five-item-reported questionnaire was applied to patients after treatment of P. vivax malaria, considering behaviours regarding to forgetfulness, carelessness as to time of administration, cessation or discontinuation of use and replication of dose. Data were collected in dichotomous and Likert scales. Reliability was assessed by Cronbach's alpha and by the contribution of each item to total. The concurrent validation was done with pill count and concordance between measures of adherence by coefficient of Kappa. Sensitivity, specificity and accuracy were also determined. RESULTS: A total of 135 patients were enrolled in the study. Adherence ranged from 63.8 to 72.7% in both psychometric measures and pill count. The responses on the Likert scale showed higher proportion of non-adherence behaviour, greater variance and concordance with pill count, as well as more sensitive to characterize the behaviour of self-medication. The internal consistency of questionnaire was moderate. Significant correlations were seen with items regarding the forgiveness or careless in taking pills in all scales. The agreement between psychometric measures and pill count was considered satisfactory. The non-adherence to malaria therapy in an endemic area of Amazon basin was 33.3%. CONCLUSION: The five-item reported questionnaire with responses on Likert scale is a feasible option for reliable estimation of adherence to malaria therapy in endemic areas. PMID- 25127887 TI - A multicenter, randomized, open-labeled study to steer immunosuppressive and antiviral therapy by measurement of virus (CMV, ADV, HSV)-specific T cells in addition to determination of trough levels of immunosuppressants in pediatric kidney allograft recipients (IVIST01-trial): study protocol for a randomized controlled trial. AB - BACKGROUND: After kidney transplantation, immunosuppressive therapy causes impaired cellular immune defense leading to an increased risk of viral complications. Trough level monitoring of immunosuppressants is insufficient to estimate the individual intensity of immunosuppression. We have already shown that virus-specific T cells (Tvis) correlate with control of virus replication as well as with the intensity of immunosuppression. The multicentre IVIST01-trial should prove that additional steering of immunosuppressive and antiviral therapy by Tvis levels leads to better graft function by avoidance of over immunosuppression (for example, viral infections) and drug toxicity (for example, nephrotoxicity). METHODS/DESIGN: The IVIST-trial starts 4 weeks after transplantation. Sixty-four pediatric kidney recipients are randomized either to a non-intervention group that is only treated conservatively or to an intervention group with additional monitoring by Tvis. The randomization is stratified by centre and cytomegalovirus (CMV) prophylaxis. In both groups the immunosuppressive medication (cyclosporine A and everolimus) is adopted in the same target range of trough levels. In the non-intervention group the immunosuppressive therapy (cyclosporine A and everolimus) is only steered by classical trough level monitoring and the antiviral therapy of a CMV infection is performed according to a standard protocol. In contrast, in the intervention group the dose of immunosuppressants is individually adopted according to Tvis levels as a direct measure of the intensity of immunosuppression in addition to classical trough level monitoring. In case of CMV infection or reactivation the antiviral management is based on the individual CMV-specific immune defense assessed by the CMV-Tvis level. Primary endpoint of the study is the glomerular filtration rate 2 years after transplantation; secondary endpoints are the number and severity of viral infections and the incidence of side effects of immunosuppressive and antiviral drugs. DISCUSSION: This IVIST01-trial will answer the question whether the new concept of steering immunosuppressive and antiviral therapy by Tvis levels leads to better future graft function. In terms of an effect-related drug monitoring, the study design aims to realize a personalization of immunosuppressive and antiviral management after transplantation. Based on the IVIST01-trial, immunomonitoring by Tvis might be incorporated into routine care after kidney transplantation. TRIAL REGISTRATION: EudraCT No: 2009-012436-32, ISRCTN89806912 (17 June 2009). PMID- 25127888 TI - In silico analysis identifies novel restriction enzyme combinations that expand reduced representation bisulfite sequencing CpG coverage. AB - BACKGROUND: Epigenetics is the study of gene expression changes that are not caused by changes in the deoxyribonucleic acid (DNA) sequence. DNA methylation is an epigenetic mark occurring in C-phosphate-G sites (CpGs) that leads to local or regional gene expression changes. Reduced-representation bisulfite sequencing (RRBS) is a technique that is used to ascertain the DNA methylation of millions of CpGs at single-nucleotide resolution. The genomic coverage of RRBS is given by the restriction enzyme combination used during the library preparation and the throughput capacity of the next-generation sequencer, which is used to read the generated libraries. The four-nucleotide cutters, MspI and TaqalphaI, are restriction enzymes commonly used in RRBS that, when combined, achieve ~12% genomic coverage. The increase in throughput of next-generation sequencers allows for novel combinations of restriction enzymes that provide higher CpG coverage. RESULTS: We performed a near-neighbor analysis of the four nucleotide sequences most frequently found within 50 nt of all genomic CpGs. This resulted in the identification of seven methylation-insensitive restriction enzymes (AluI, BfaI, HaeIII, HpyCH4V, MluCI, MseI, and MspI) that shared similar restriction conditions suitable for RRBS library preparation. We report that the use of two or three enzyme combinations increases the theoretical epigenome coverage to almost half of the human genome. CONCLUSIONS: We provide the enzyme combinations that are more likely to increase the CpG coverage in human, rat, and mouse genomes. PMID- 25127889 TI - SPARQLGraph: a web-based platform for graphically querying biological Semantic Web databases. AB - BACKGROUND: Semantic Web has established itself as a framework for using and sharing data across applications and database boundaries. Here, we present a web based platform for querying biological Semantic Web databases in a graphical way. RESULTS: SPARQLGraph offers an intuitive drag & drop query builder, which converts the visual graph into a query and executes it on a public endpoint. The tool integrates several publicly available Semantic Web databases, including the databases of the just recently released EBI RDF platform. Furthermore, it provides several predefined template queries for answering biological questions. Users can easily create and save new query graphs, which can also be shared with other researchers. CONCLUSIONS: This new graphical way of creating queries for biological Semantic Web databases considerably facilitates usability as it removes the requirement of knowing specific query languages and database structures. The system is freely available at http://sparqlgraph.i-med.ac.at. PMID- 25127890 TI - Immigrants' use of primary health care services for mental health problems. AB - BACKGROUND: Equity in health care across all social groups is a major goal in health care policy. Immigrants may experience more mental health problems than natives, but we do not know the extent to which they seek help from primary health care services. This study aimed to determine a) the rate immigrants use primary health care services for mental health problems compared with Norwegians and b) the association between length of stay, reason for immigration and service use among immigrants. METHODS: National register data covering all residents in Norway and all consultations with primary health care services were used. We conducted logistic regression analyses to compare Norwegians' with Polish, Swedish, German, Pakistani and Iraqi immigrants' odds of having had a consultation for a mental health problem (P-consultation). RESULTS: After accounting for background variables, all immigrants groups, except Iraqi men had lower odds of a P-consultation than their Norwegian counterparts. A shorter length of stay was associated with lower odds of a P-consultation. CONCLUSIONS: Service use varies by country of origin and patterns are different for men and women. There was some evidence of a possible 'healthy migrant worker' effect among the European groups. Together with previous research, our findings however, suggest that Iraqi women and Pakistanis in particular, may experience barriers in accessing care for mental health problems. PMID- 25127893 TI - A novel sonochemical synthesis of antlerite nanorods. AB - Antlerite - Cu3(OH)4SO4 was prepared, for the first time, by the sonochemical method from an aqueous solution of CuSO4, without any additives. The source of OH(-) is a result of protonation of SO4(2-) forming HSO4(-) and OH(-). The extreme local conditions inside the cavity that are developed during the bubble collapse (pressure is above 1000atm and the temperature is higher than 5000K) lead to the formation of the crystalline mineral. A suggested mechanism for the mineral formation is proposed. Due to the collapse of the bubbles, the distances between the opposite charge Cu(2+) and SO4(2-) ions is shortened and a crystallization process is initiated. In addition, the reaction is a one-step process with short irradiation time of less than 30min. The chemo-physical analysis of the sonochemically obtained product has revealed the presence of single phase antlerite nanorods. PMID- 25127891 TI - Comparative effectiveness of approved first-line anti-angiogenic and molecularly targeted therapeutic agents in the treatment of good and intermediate risk metastatic clear cell renal cell carcinoma. AB - BACKGROUND: Based on improved clinical outcomes in randomized controlled clinical trials (RCTs) the FDA and EMA have approved bevacizumab with interferon, sunitinib, and pazopanib in the first-line treatment of low to intermediate risk metastatic clear cell renal cell carcinoma (mRCC). However, there is little comparative data to help in choosing the most effective drug among these agents. METHODS: We performed an indirect comparative effectiveness analysis of the pivotal RCTs of bevacizumab with interferon, sunitinib, or pazopanib compared to one another or interferon alone in first-line treatment of metastatic or advanced RCC. Endpoints of interest were overall survival (OS), progression free survival (PFS), and response rate (RR). Adverse events were also examined. RESULTS: The meta-estimate of the hazard ratio (95% confidence interval) for OS for bevacizumab with interferon vs. interferon alone was 0.86 (0.76-0.97), for sunitinib vs. interferon alone was 0.82 (0.67-1.00), for pazopanib vs. interferon alone was 0.74 (0.57-0.97), for sunitinib vs. bevacizumab with interferon was 0.95 (0.75-1.20), for pazopanib vs. bevacizumab with interferon was 0.86 (0.64 1.16), and for pazopanib vs. sunitinib was 0.91 (0.76-1.08). Similarly, bevacizumab with interferon, sunitinib, or pazopanib had better PFS and RR than interferon alone. Sunitinib and pazopanib had better RR than bevacizumab with interferon and there was suggestive evidence pazopanib may outperform sunitinib in terms of RR. CONCLUSIONS: Bevacizumab with interferon, sunitinib, and pazopanib are adequate first-line options in treatment of mRCC. Interferon alone should not be considered an optimal first-line treatment. PMID- 25127894 TI - [Schizophrenia and informed consent to research]. AB - CONTEXT: Informed consent to research remains a complex issue, while sometimes staying difficult to obtain, even in the general population. This problem may be maximized with patients suffering from schizophrenia. OBJECTIVE: This paper summarizes available data in the literature about informed consent for research involving patients suffering from schizophrenia. METHOD: Medline and Google Scholar searches were conducted using the following MESH terms: schizophrenia, informed consent and research. RESULTS: Studies using dedicated standardized scales (e.g. MacCAT-CR) revealed a decrease in the capacity to consent of patients with schizophrenia when compared with healthy individuals. Keeping in mind that schizophrenia is an heterogeneous disorder, patients with the lowest insight as well as those with the most severe cognitive symptoms appeared more impaired in their capacity to consent. Such a poor capacity to understand and consent to trials was shown linked with alterations in decision-making. For these specific patients, interventions may be set up to increase their capacity to consent. Various strategies were proposed: enhanced consent forms, extended discussion, test/feedback method or multimedia interventions. Among them, interventions relying on communication and the growing field of information technologies (e.g. web-based tools) seem promising. Finally, associations grouping families and patients (like the French Association UNAFAM) may facilitate the involvement of patients in research programs with safer conditions. CONCLUSION: Patients suffering from schizophrenia appear able to consent to research programs when suitable interventions are proposed. Further studies are now needed to optimize and individualize such interventions. PMID- 25127892 TI - Mercury in fish and adverse reproductive outcomes: results from South Carolina. AB - BACKGROUND: Mercury is a metal with widespread distribution in aquatic ecosystems and significant neurodevelopmental toxicity in humans. Fish biomonitoring for total mercury has been conducted in South Carolina (SC) since 1976, and consumption advisories have been posted for many SC waterways. However, there is limited information on the potential reproductive impacts of mercury due to recreational or subsistence fish consumption. METHODS: To address this issue, geocoded residential locations for live births from the Vital Statistics Registry (1995-2005, N = 362,625) were linked with spatially interpolated total mercury concentrations in fish to estimate potential mercury exposure from consumption of locally caught fish. Generalized estimating equations were used to test the hypothesis that risk of low birth weight (LBW, <2,500 grams) or preterm birth (PTB, < 37 weeks clinical gestation) was greater among women living in areas with elevated total mercury in fish, after adjustment for confounding. Separate analyses estimated term LBW and PTB risks using residential proximity to rivers with fish consumption advisories to characterize exposure. RESULTS: Term LBW was more likely among women residing in areas in the upper quartile of predicted total mercury in fish (odds ratio [OR] = 1.04; 95% confidence interval [CI]: 1.00 1.09) or within 8 kilometers of a river with a 'do not eat' fish advisory (1.05; 1.00-1.11) compared to the lowest quartile, or rivers without fish consumption restrictions, respectively. When stratified by race, risks for term LBW or PTB were 10-18% more likely among African-American (AA) mothers living in areas with the highest total fish mercury concentrations. CONCLUSIONS: To our knowledge, this is the first study to examine the relationship between fish total mercury concentrations and adverse reproductive outcomes in a large population-based sample that included AA women. The ecologic nature of exposure assessment in this study precludes causal inference. However, the results suggest a need for more detailed investigations to characterize patterns of local fish consumption and potential dose-response relationships between mercury exposure and adverse reproductive outcomes, particularly among AA mothers. PMID- 25127895 TI - [Assessment of mental states at risk of psychotic transition: validation of the French version of the CAARMS]. AB - This article aims to present the validation study of the French version of the Comprehensive Assessment of at risk mental states (CAARMS), an interview that seeks to determine whether young adults criteria for at-risk (AR) mental states, or psychosis. We assessed 40 young subjects, 15 were considered as "prodromal" (Prd) and 10 as experiencing a first episode of psychosis (PEP) by our expert clinician at the center - centre d'evaluation des jeunes adultes et adolescents, University Hospital Centre, Paris - and 15 were healthy controls matched for age and sex. When assessed with the CAARMS, 73 % (n=11) of the prodromal subjects reached the criteria for AR mental state, four subjects did not reach the criteria for AR, nor psychosis (P) and 100 % of the PEP reached the criteria for P. The three groups were significantly different on CAARMS total score (P<0.001) and subscores ; Prd subjects had intermediate scores between PEP (P<0.001) and controls (P<0.001) scores, PEP showing the highest scores. Post-hoc analysis showed that Prd significantly differed from Controls on each subscale (P<0.001) and that Prd differed from PEP on the "positive symptoms" subscale (P<0.001), as well as on "behavioural change" (P=0.021), owing to difference on the item "impaired role function". We used the brief psychiatric rating scale 24 items with anchor (BPRS24-EA) in addition to with the CAARMS, the AR group showed intermediate scores between controls and P subjects. Total scores of both scales were correlated (r=0.408 ; P=0.043) and the BPRS24-EA "positive symptoms" score was correlated with CAARMS' scores on the "Positive symptoms" subscale (r=0.456, P=0.022), "emotional disturbance" (r=0.506, P=0.01), and "behavioural change" (r=0.666 P=0.001). We found no correlation between BPRS negative and depression subscales and any of the CAARMS' subscales. When looking at its reliability, reliability coefficients (Cronbach's alpha) showed excellent reliability for "positive symptoms", "emotional disturbance", "behavioural change" and "general psychopathology" (respectively r=0.82, 0.75, 0.78, 0.84, 0.83) and moderate reliability for "cognitive change", "negative symptoms" and "motor/physical change" (respectively r=0.39, 0.59, 0.43). Overall, analysis of the results of construct validity, concurrent validity and reliability of the CAARMS indicates that the French version is valid and reliable. It is now available to develop and implement early detection programs in French speaking countries. PMID- 25127896 TI - [Clinical presentation of Moroccan cases with Alzheimer's disease]. AB - INTRODUCTION: The diagnostic approach for Alzheimer's disease is based on the presence of cerebral atrophy combined with the score of the mini-examination of the mental state. In this context, this study was conducted to assess the correlation between imaging and neuropsychological testing for cases of early onset and late-onset Alzheimer's disease. AIM OF THE STUDY: Analysis of the clinical and paraclinical aspects of Moroccan cases with Alzheimer's disease. METHODS: Seventeen sporadic cases and 8 family cases were seen at the memory clinic of the Neurology Department of the University of Casablanca Ibn Rochd Hospital. A family history was obtained through a clinical interview of the patient and a yes or no self-reporting questionnaire from the guardian or other family member. The disease was considered familial if at least one additional first degree relative suffered from early-onset AD-type dementia. All patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging and laboratory tests. Written consent was obtained from the patients and their guardians prior to the study. RESULTS: In our study of 25 individuals, the observed mean age of AD patients was 64.52 +/- 9.30 and we observed a slight female predominance (56% versus 44%). In addition, we found a prevalence of AD of approximately 20%, increasing with age, in the population below 60 years of age. Approximately half of our patients (48%) had a score lower than 10 and were affected by severe insanity, while 28% were affected by moderate severe insanity and 24% were light to moderately insane. Twenty-five patients underwent neuroimaging, 18 of whom were assessed by MRI, while 7 were assessed by CT. All patients had hippocampal atrophy, which progressed to affect others brain regions. The blood tests showed no abnormalities in the 25 enrolled AD cases. DISCUSSION: Age is undoubtedly the main risk factor for AD; this is also the true for our cases where advanced age was responsible for the exponential increase of the disease's frequency; it reached a peak in the age group of 60-69 years. The AD diagnosis approach is based on the presence of cerebral atrophy combined with the score of the mini-examination of the mental state (MMSE). In our study, in addition to the MMSE, depending on the level of education, the clinician used other tests that do not necessarily require a level of education such as the BEC96, visual short-term or digital memory assessment, work memory assessment, language assessment test (DO80) and apraxia. Neuropsychological examination of the cases with a score of less than 10 showed severe cognitive impairment. The cases presented memory and language impairments, aphasia, visual spatial disorientation, decreased autonomy, executive dysfunction and praxis deficits, all major causes of severe dementia. Neuroimaging revealed hippocampal and cortical atrophy. Correlated with the other studies that aimed to establish links between brain alterations and neuropsychological disorders, we can conclude that a higher level of atrophy reflects a decrease in neuropsychological performance. PMID- 25127897 TI - [Epigenetics of schizophrenia: a review]. AB - BACKGROUND: Schizophrenia is a frequent and disabling disease associated with heterogeneous psychiatric phenotypes. It emerges during childhood, adolescence or young adulthood and has dramatic consequences for the affected individuals, causing considerable familial and social burden, as well as increasing health expenses. Although some progress has been made in the understanding of their physiopathology, many questions remain unsolved, and the disease is still poorly understood. The prevailing hypothesis regarding psychotic disorders proposes that a combination of genetic and/or environmental factors, during critical periods of brain development increases the risk for these illnesses. Epigenetic regulations, such as DNA methylation, can mediate gene x environment interactions at the level of the genome and may provide a potential substrate to explain the variability in symptom severity and family heritability. Initially, epigenetics was used to design mitotic and meiotic changes in gene transcription that could not be attributed to genetic mutations. It referred later to changes in the epigenome not transmitted through the germline. Thus, epigenetics refers to a wide range of molecular mechanisms including DNA methylation of cytosine residues in CpG dinucleotides and post-translational histone modifications. These mechanisms alter the way the transcriptional factors bind the DNA, modulating its expression. Prenatal and postnatal environmental factors may affect these epigenetics factors, having responsability in long-term DNA transcription, and influencing the development of psychiatric disorders. OBJECT: The object of this review is to present the state of knowledge in epigenetics of schizophrenia, outlining the most recent findings in the matter. METHODS: We did so using Pubmed, researching words such as 'epigenetics', 'epigenetic', 'schizophrenia', 'psychosis', 'psychiatric'. This review summarizes evidences mostly for two epigenetic mechanisms: DNA methylation and post-translational histone modifications. RESULTS: First, in terms of epidemiology and transmission, the theoretical model of epigenetics applies to schizophrenia. Then, most environmental factors that have proved a link with this disease, may generate epigenetic mechanisms. Next, mutations have been found in regions implied in epigenetic mechanism among populations with schizophrenia. Some epigenetic alterations in DNA regions have been previously linked with neurodevelopmental abnormalities. In psychosis, some authors have found methylation differences in COMT gene, in reelin gene and in some genes implicated in dopaminergic, serotoninergic, GABAergic and glutamatergic pathways. Histone modifications have been described, in particular the H3L4 histone methylation. Finally, we tried to underline the difficulties in epigenetic research, notably in psychiatry, and the limits in this matter. CONCLUSION: The epigenetic field may explain a lot of questions around the physiopathology of the complex psychiatric disease that is schizophrenia. It may be a substratum to the prevailing hypothesis of gene x environment interaction. The research in the matter is definitely expanding. It justifies easily the need to improve the effort in the domain to overpass some limits inherent to the matter. PMID- 25127898 TI - [The link between aggressive behavior and depression in adolescence. A cross sectional study conducted in the psychiatric emergency unit at the Sainte-Anne hospital]. AB - INTRODUCTION: The link between depression and aggressive behavior in adults has been found in many studies. In adolescents, this relationship is still controversial. Several studies point out that irritability is a key symptom in adolescent depressed. Few studies have analyzed precisely the kind of aggressive behavior. This study sets out to assess the relationship between aggressive behavior and depressive affects in adolescents. We also pay attention in this population to hopelessness feelings, anxiety, global functioning and the type of aggressive behavior. METHOD: This is a descriptive and observational cross sectional study. Data was collected from 49 successive adolescents admitted for a 24-hour evaluation in the emergency department of the Sainte-Anne psychiatric hospital. The inclusion period was from February to April 2012, with age limits between 15 and 18. For each patient, the clinician completed with the parents or other caregivers the Modified Overt Aggressive Scale (MOAS) searching for existence of aggressive behavior in the week prior to the consultation. The population was divided into two groups: P- group when the MOAS score was < 3 and the P+ group when the MOAS score was >= 3. The Global Assessment of Functioning Scale and Adolescent Depression Rating Scale for clinicians (ADRSc) were also completed. Each patient completed the self-report Buss-Perry Aggression Questionnaire (QA), the Beck Hopelessness scale and the Adolescent Depression Rating Scale for patients (ADRSp). RESULTS: Forty-nine adolescents with a median age of 16 years and 4 months participated. The first reason for consultation was depressive symptoms, followed by disruptive behavior. The analysis was conducted on 39 questionnaires. The demographic profile of the two groups was similar. We did not find any significant difference between the groups P+ and P- on ADRSc scores and secondary criteria. However, we found higher scores in the QA in the more depressed patient, especially a higher hostility score in this sample. In the subgroup analysis: as expected self-aggressive behavior was associated with a higher depression score, more hospitalization and a poor global functioning score. Surprisingly, the patients who showed physical aggression against others had a better prognosis and lower depression scores. DISCUSSION: The study did not conclude on the link between aggressive behavior and depression in this population. The adolescent hostility appears more characteristic of depression compared to other dimensions of aggressivity (anger, verbal aggression, physical aggression) in adolescents. Physical aggression against others appeared not only less typical in depression but was also associated with a better global functioning. Clinicians should pay particular attention to the kind of aggressive behavior in clinical evaluations of adolescents in an emergency context. PMID- 25127899 TI - Optimal beam arrangement for pulmonary ventilation image-guided intensity modulated radiotherapy for lung cancer. AB - BACKGROUND: The principal aim of this study was to evaluate the feasibility of incorporating four-dimensional (4D)-computed tomography (CT)-based functional information into treatment planning and to evaluate the potential benefits of individualized beam setups to better protect lung functionality in patients with non-small cell lung cancer (NSCLC). METHODS: Peak-exhale and peak-inhale CT scans were carried out in 16 patients with NSCLC treated with intensity-modulated radiotherapy (IMRT). 4D-CT-based ventilation information was generated from the two sets of CT images using deformable image registration. Four kinds of IMRT plans were generated for each patient: two anatomic plans without incorporation of ventilation information, and two functional plans with ventilation information, using either five equally spaced beams (FESB) or five manually optimized beams (FMOB). The dosimetric parameters of the plans were compared in terms of target and normal tissue structures, with special focus on dose delivered to total lung and functional lung. RESULTS: In both the anatomic and functional plans, the percentages of both the functional and total lung regions irradiated at V5, V10, and V20 (percentage volume irradiated to >5, >10 and >20 Gy, respectively) were significantly lower for FMOB compared with FESB (P < 0.05), but there was no significant difference for V30 (P > 0.05). Compared with FESB, a greater degree of sparing of the functional lung was achieved in functional IMRT plans with optimal beam arrangement, without compromising target volume coverage or the irradiated volume of organs at risk, such as the spinal cord, esophagus, and heart. CONCLUSIONS: Pulmonary ventilation image-guided IMRT planning with further optimization of beam arrangements improves the preservation of functional lung in patients with NSCLC. PMID- 25127900 TI - Therapeutic targeting of angiogenesis with a recombinant CTT peptide-endostatin mimic-kringle 5 protein. AB - Angiogenesis is required for tumor growth and metastasis, and targeting angiogenesis is a novel anticancer strategy. However, cancer development is a complex multistep process, and single antiangiogenic agents have limited therapeutic efficacy. Here, we report a triple fusion protein, namely CTT peptide endostatin mimic-kringle 5 (AARP), consisting of MMP-2/9-selective inhibitory peptide (CTT peptide) and well-known endogenous antiangiogenic agents (endostatin mimic and kringle 5), which can simultaneously target matrix metalloproteinases (MMP) and endothelial cells, blocking their actions. AARP was bacterially expressed, and biologic activity of purified AARP was assessed. AARP could significantly inhibit the enzymatic activity of MMP-2/9, proliferation, migration, and tube formation of endothelial cells in vitro. The antitumor activity of AARP was shown in a concentration-dependent manner when injected i.p. into immunodeficient mice bearing multidrug-resistant human epidermoid carcinomas (KB), and AARP is superior to clinical grade endostatin in inhibiting KB xenograft growth. In mouse models of Lewis lung carcinoma (LLC) and hepatoma H22, when given as a single dose, AARP is highly effective for reducing tumor growth, angiogenesis, and metastasis, and increasing survival time. AARP possessed significantly greater antiangiogenic activity than endostatin mimic, CTT peptide kringle 5 (RK5) both in vitro and in vivo. Compared with conventional chemotherapeutic agents (cyclophosphamide and paclitaxel), AARP is also effective. More importantly, AARP is cytocompatible and no tissue toxicity could be observed after large dose administration. Taken together, our findings suggest AARP is a highly effective, safe, and more potent antiangiogenic agent for blocking tumor angiogenesis and metastasis, and warrants further testing for clinical applications. PMID- 25127902 TI - Over-testing for heparin induced thrombocytopenia in hospitalized patients. AB - Heparin induced thrombocytopenia (HIT) is a pro-thrombotic and potentially fatal complication of heparin therapy. Its diagnosis rests on high clinical probability and the laboratory demonstration of anti-PF4/heparin antibodies. The high prevalence of thrombocytopenia in hospitalized patients and the high sensitivity but low specificity of immunoassays for HIT antibodies can lead to over-testing and over-diagnosis. We conducted a study to review HIT screening practices in a tertiary care setting. We reviewed 63 consecutive patients undergoing testing for anti-PF4/heparin antibodies over 3 months. Pre-test probability for HIT was calculated using the 4T score. Sixty three patients underwent testing for anti PF4/heparin antibodies. Twenty one had been admitted for cardiovascular surgery, 5 for other surgery and 35 for non-surgical indications. Twenty nine patients (46 %) had low pre- test probability, twenty three (36.5 %) had intermediate probability, and eleven (17.4 %) had high pre-test probability of having HIT. Anti-PF4/heparin ELISA was positive in 8 of 63 patients. SRA was ordered for 16 patients and was positive in 5. Only five patients were diagnosed and treated for HIT. Over-testing for HIT is highly prevalent in a tertiary care setting. This increases cost and exposes patients to expensive anti-coagulation with its attendant risk of hemorrhage. The 4Ts score has been shown to have high sensitivity and may be used to rule out HIT in most situations, although its utility depends on subjective analysis. Consistently applying this in practice could minimize over-testing and facilitate safer, cost-effective care. PMID- 25127903 TI - Thromboelastography defines late hypercoagulability after TBI: a pilot study. AB - INTRODUCTION: Traumatic brain injury (TBI) is associated with a hypercoagulable state, the mechanism and duration of which remain unclear. We sought to determine whether thromboelastography (TEG) analysis could identify the hypercoagulable state after TBI, as defined by elevations in maximal amplitude (MA), thrombus generation (TG), G value (G), and alpha angle (alphaA). METHODS: Patients with moderate-severe TBI, defined primarily as a GCS <12, admitted between 1/2012 and 8/2013 were eligible for enrolment in this prospective cohort study. TEG profiles were obtained between 0-24 h (T1), 24-48 h (T2), 48-72 h (T3), 72-96 h (T4), and 96-120 h (T5) after admission. Early TEG was defined as 0-48 h, and late TEG was defined as >48 h. RESULTS: Twenty five patients (80 % men) and 7 age- and sex matched control subjects were studied. Median age was 38 years (range 18-85). Early MA was [63.6 mm (60.5, 67.4)] versus late MA [69.9 mm (65.2,73.9); p = 0.02], early TG was [763.3 mm/min (712.8, 816.2)] versus late TG [835.9 mm/min (791.2,888.3); p = 0.02], and early G was [8.8 d/cm(2) (7.7,10.4)] versus late G [11.6 d/cm(2) (9.4,14.1); p = 0.02]. Study patients had higher MA (p = 0.02), TG (p = 0.03), and G (p = 0.02) values at T5 compared to controls. There was a linear increase per day of MA by 2.6 mm (p = 0.001), TG 31.9 mm/min (p <= 0.001), and G value by 1.3 d/cm(2) (p <= 0.001) when clustered by pairs in regression analysis. Lower MA values trended toward home discharge (p = 0.08). CONCLUSION: The data suggest a progressive and delayed hypercoagulable state observed days after initial TBI. The hypercoagulable state may reflect excess platelet activity. PMID- 25127904 TI - Risk of reintubation in neurosurgical patients. AB - BACKGROUND: Reintubation among neurosurgical patients is poorly characterized. The aim of this study was to delineate the rate of reintubation among neurosurgical patients. In addition, we seek to characterize the patient demographic features, comorbidities, and surgical characteristics that may be associated with reintubation among neurosurgical patients. METHODS: This is a retrospective cohort study conducted in the setting of hospitals participating in the American College of Surgeons' National Surgical Quality Improvement Program between 2005 and 2010. All adult patients undergoing neurosurgery under general anesthesia were included. Exclusion criteria were preoperative mechanical ventilation or pneumonia prior to surgery. Reintubation was defined as placement of an endotracheal tube or mechanical ventilation within 48 h after surgery. RESULTS: Among 17,483 eligible patients, 74 (0.42 %; 95 % CI 0.33-0.52 %) required reintubation within 48 h of surgery. In multiple logistic regression, the following were associated with increased risk of reintubation: age >65 years (OR 2.1; 95 % CI 1.3-3.4), preoperative renal failure (OR 2.9; 95 % CI 1.0-8.5), quadriplegia (OR 8.2; 95 % CI 3.3-20.3), COPD (OR 2.1; 95 % CI 1.0-4.3), operative time >3 h (OR 2.9; 95 % CI 1.8-4.8), and higher ASA class (OR per point, 2.1; 95 % CI 1.4-3.1). Spinal surgery was found to be protective relative to cranial neurosurgery or endarterectomy (OR 0.3; 95 % CI 0.2-0.5). CONCLUSIONS: Reintubation after neurosurgery is associated with older patients with a greater number of comorbidities. In particular, renal, pulmonary, and severe neurologic comorbidities; longer operative duration; and cranial, rather than spinal, pathology were associated with increased risk for reintubation. These findings may be helpful in triage decisions regarding postoperative intensity of care and monitoring. PMID- 25127905 TI - Long-term outcome and quality of life after craniectomy in speech-dominant swollen middle cerebral artery infarction. AB - BACKGROUND: Decompressive craniectomy in malignant middle cerebral artery infarction (MMCAI) reduces mortality. Whether speech-dominant side infarction results in less favorable outcome is unclear. This study compared functional outcome, quality of life, and mental health among patients with speech-dominant and non-dominant side infarction. METHODS: All patients undergoing decompressive craniectomy for MMCAI were included. Demographics, side of infarction, and speech dominant hemisphere were recorded. Outcome at follow-up was assessed by global functioning (modified Rankin Scale score), neurological impairment (National Institutes of Health Stroke Scale score), dependency (Barthel Index), anxiety and depression (Hospital Anxiety and Depression scale), and quality of life (Short Form-36). RESULTS: Twenty-nine out of 45 patients (mean age +/- SD, 48.1 +/- 11.6 years; 58 % male) were alive at follow-up, and 26 were eligible for analysis [follow-up, median (interquartile range): 66 months (32-93)]. The speech-dominant hemisphere was affected in 13 patients. Outcome for patients with speech-dominant and non-dominant side MMCAI was similar regarding neurological impairment (National Institutes of Health Stroke Scale score, mean +/- SD: 10.3 +/- 7.0 vs. 8.9 +/- 2.7, respectively; p = 0.51), global functioning [modified Rankin Scale score, median (IQR): 3.0 [2-4] vs. 4.0 [3-4]; p = 0.34], dependence (Barthel Index, mean +/- SD: 16.2 +/- 5.0 vs. 13.1 +/- 4.8; p = 0.12), and anxiety and depression (Hospital Anxiety and Depression scale, mean +/- SD: anxiety, 5.0 +/- 4.5 vs. 7.3 +/- 5.8; p = 0.30; depression, 5.0 +/- 5.2 vs. 5.9 +/- 3.9; p = 0.62). The mean quality of life scores (Short Form-36) were not significantly different between the groups. CONCLUSIONS: There was no statistical or clinical difference in functional outcome and quality of life in patients with speech dominant compared to non-dominant side infarction. The side affected should not influence suitability for decompressive craniectomy. PMID- 25127906 TI - Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data. AB - BACKGROUND: Infectious disease surveillance is a process the product of which reflects both actual disease trends and public awareness of the disease. Decisions made by patients, health care providers, and public health professionals about seeking and providing health care and about reporting cases to health authorities are all influenced by the information environment, which changes constantly. Biases are therefore imbedded in surveillance systems; these biases need to be characterized to provide better situational awareness for decision-making purposes. Our goal is to develop a statistical framework to characterize influenza surveillance systems, particularly their correlation with the information environment. METHODS: We identified Hong Kong influenza surveillance data systems covering healthcare providers, laboratories, daycare centers and residential care homes for the elderly. A Bayesian hierarchical statistical model was developed to examine the statistical relationships between the influenza surveillance data and the information environment represented by alerts from HealthMap and web queries from Google. Different models were fitted for non-pandemic and pandemic periods and model goodness-of-fit was assessed using common model selection procedures. RESULTS: Some surveillance systems - especially ad hoc systems developed in response to the pandemic flu outbreak - are more correlated with the information environment than others. General practitioner (percentage of influenza-like-illness related patient visits among all patient visits) and laboratory (percentage of specimen tested positive) seem to proportionally reflect the actual disease trends and are less representative of the information environment. Surveillance systems using influenza-specific code for reporting tend to reflect biases of both healthcare seekers and providers. CONCLUSIONS: This study shows certain influenza surveillance systems are less correlated with the information environment than others, and therefore, might represent more reliable indicators of disease activity in future outbreaks. Although the patterns identified in this study might change in future outbreaks, the potential susceptibility of surveillance data is likely to persist in the future, and should be considered when interpreting surveillance data. PMID- 25127907 TI - The effect of transforming growth factor beta1 on the crosstalk between autophagy and apoptosis in the annulus fibrosus cells under serum deprivation. AB - Autophagy and apoptosis are important in maintaining the metabolic homeostasis of intervertebral disc cells, and transforming growth factor-beta1 (TGF-beta1) is able to delay intervertebral disc degeneration. This study determined the effect of TGF-beta1 on the crosstalk between autophagy and apoptosis in the disc cells, with the aim to provide molecular mechanism support for the prevention and treatment of disc degeneration. Annulus fibrosus (AF) cells were isolated and cultured under serum starvation. 10 ng/mL TGF-beta1 reduced the apoptosis incidence in the cells under serum starvation for 48 h, down-regulated the autophagy incidence in the cells pretreated with 3-methyladenine (3-MA) or Bafilomycin A (Baf A), partly rescued the increased apoptosis incidence in the cells pretreated with 3-MA, while further reduced the decreased apoptosis incidence in the cells pretreated with Baf A. Meanwhile, TGF-beta1 down-regulated the expressions of autophagic and apoptotic markers in the cells under starvation, partly down-regulated the expressions of Beclin-1, LC3 II/I and cleaved caspase-3 in the cells pretreated with 3-MA or Baf A, while significantly decreased the expression of Bax/Bcl-2 in the cells pretreated with Baf A. 3-MA blocked the phosphorylation of both AKT and mTOR and partly reduced the inhibitory effect of TGF-beta1 on the expression of LC3 II/I and cleaved caspase 3. TGF-beta1 enhanced the expression of p-ERK1/2 and down-regulated the expressions of LC3 II/I and cleaved caspase-3. U0126 partly reversed this inhibitory effect of TGF-beta1. In conclusion, TGF-beta1 protected against apoptosis of AF cells under starvation through down-regulating excessive autophagy. PI3K-AKT-mTOR and MAPK-ERK1/2 were the possible signaling pathways involved in this process. PMID- 25127908 TI - Delayed versus early motion after arthroscopic rotator cuff repair: a meta analysis. AB - BACKGROUND: We conducted a meta-analysis of randomized trials to compare delayed vs early motion therapy on function after arthroscopic rotator cuff repair. METHODS: We searched 4 electronic databases (Medline, Embase, Cochrane, and Physiotherapy Evidence Database [PEDro]). The methodologic quality of the included studies was assessed, and the relevant data were extracted. Data were pooled for functional outcomes, rotator cuff tear recurrence, and shoulder range of motion. Complications were reported descriptively. RESULTS: Three level I and 1 level II randomized trials were eligible and included. Pooled analysis revealed no statistically significant differences in American Shoulder and Elbow Surgeons scores between delayed vs early motion rehabilitation (mean difference [MD], 1.4; 95% confidence interval [CI], -1.8 to 4.7; P = .38, I(2) = 34%). The risk of retears after surgery did not differ statistically between treatment groups (risk ratio, 1.01; 95% CI, 0.63-1.64; P = .95). Early passive motion led to a statistically significant, although clinically unimportant, improvement in forward elevation between groups (MD, -1 degrees ; 95% CI, -2 degrees to 0 degrees ; P = 0.04, I(2) = 0%). There was no difference in external rotation between treatment groups (MD, 1 degrees ; 95% CI, -2 degrees to 4 degrees ; P = 0.63, I(2) = 0%). None of the included studies identified any cases of postoperative shoulder stiffness. CONCLUSIONS: The current meta-analysis did not identify any significant differences in functional outcomes and relative risks of recurrent tears between delayed and early motion in patients undergoing arthroscopic rotator cuff repairs. A statistically significant difference in forward elevation range of motion was identified; however, this difference is likely clinically unimportant. PMID- 25127909 TI - A preoperative scoring system to select patients for arthroscopic subacromial decompression. AB - BACKGROUND: This study investigated the clinical and radiographic factors that influence outcome after arthroscopic subacromial decompression (ASAD) for shoulder impingement syndrome. The goal was to develop a new preoperative scoring system to identify patients who would have a prompt and sustained benefit from ASAD. METHODS: We prospectively reviewed 112 consecutive patients with impingement syndrome who subsequently underwent ASAD. The Oxford Shoulder Score (OSS) was recorded preoperatively and 3 and 12 months postoperatively. A statistically significant improvement in OSS at 3 months after surgery was considered a good outcome. RESULTS: The variables associated with good outcome were shoulder pain with overhead activities, persistent symptoms for more than 6 months, symptoms persistent despite a 3-month course of supervised physiotherapy, consistently positive Hawkins test result, radiologic changes of impingement on both acromion and humerus in the subacromial region, and improvement for more than 1 week after a steroid injection. These 6 criteria were combined into a single score for this study, termed the preoperative score (PrOS). Sixty-two patients who had been symptomatic for 1 year with a preoperative score of 5 to 6 showed significant improvement in OSS at 3 months after surgery (P < .001). Thirty-eight patients with a score 3 to 4 had no statistically significant improvement in OSS at 3 months but had a further slight improvement at 1 year. Twelve patients with a score of <=2 had no significant improvement in OSS at 3 months or 1 year. CONCLUSION: This scoring system can identify patients who would have a prompt benefit from ASAD. The impact of surgery in patients with a PrOS of <=4 points is questionable. PMID- 25127910 TI - Case report: misdiagnosed olecranon bursitis: pyoderma gangrenosum. PMID- 25127911 TI - Successful treatment of humeral giant aneurysmal bone cyst: value of the induced membrane reconstruction technique. PMID- 25127912 TI - Arthroscopic repair of an avulsed latissimus dorsi tendon transfer for massive, irreparable rotator cuff tear: a report of two cases. PMID- 25127913 TI - Regarding "meta-analysis comparing single-row and double-row repair techniques in the arthroscopic treatment of rotator cuff tears". PMID- 25127914 TI - Response to "meta-analysis comparing single-row and double-row repair techniques in the arthroscopic treatment of rotator cuff tears". PMID- 25127915 TI - Effect of a medical toxicology admitting service on length of stay, cost, and mortality among inpatients discharged with poisoning-related diagnoses. AB - There are no published studies that have compared quality outcomes of hospitalized poisoned patients primarily under the care of physician medical toxicologists to patients treated by non-toxicologists. We hypothesized that inpatients primarily cared for by medical toxicologists would exhibit shorter lengths of stay (LOS), lower costs, and decreased mortality. Patients discharged in 2010 and 2011 from seven hospitals within the same health care system and greater metropolitan area with Medicare severity diagnosis-related groups for "poisoning and toxic effects of drugs" with and without major comorbidities or complications (917 & 918, respectively) were identified from a Premier(r) database. The database contained severity-weighted comparisons between expected and observed outcomes for each patient. Outcome parameters were differences between expected and observed LOS, cost, and percent mortality. These were then compared among groups of patients primarily admitted and cared for by (1) medical toxicologists at one hospital (Banner Good Samaritan Medical Center, BGS), (2) non-toxicologists at BGS, and (3) non-toxicologists at six other hospitals. Records of 3,581 patients contained complete data for assessment of at least one outcome measure. Patients cared for by medical toxicologists experienced favorable differences in LOS, costs, and mortality compared with other patient groups (p < 0.001). If patients cared for by non-toxicologists had experienced similar differences in observed over expected values for LOS, cost, and mortality as those cared for by medical toxicologists, there would have been a median savings of 1,483 hospital days, $4.269 million, and a significant decrease in mortality during the 2-year study period. Differences between observed and expected LOS, cost, and mortality in patients primarily cared for by medical toxicologists were significantly better than in patients cared for by non toxicologists, regardless of facility. These data suggest that significant reductions in patient hospital days, costs, and mortality are possible when medical toxicologists directly care for hospitalized patients. PMID- 25127917 TI - The diagnosis of febrile urinary tract infection in children may be facilitated by urinary biomarkers. AB - BACKGROUND: We prospectively assessed the feasibility of two urinary markers of renal injury as potential diagnostic tests for acute febrile urinary tract infection (UTI) and subsequent renal scarring. METHODS: The patient cohort comprised children aged 0 to 4 years who visited the emergency room. The children were divided into three groups, namely, a febrile UTI (fUTI), febrile control (FC) and a non-febrile control (NFC) group, respectively, which were matched for sex and age. An enzyme-linked immunosorbent assay for neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) was performed on urine collected from each child. The urine levels of both markers were compared between the three groups, and the diagnostic accuracy was determined based on the area under the receiver-operator characteristic curve (AUC). In the fUTI group, the predictability of subsequent renal scarring was assessed by associating urinary levels with dimercaptosuccinic acid findings 6 months after an UTI episode. RESULTS: Significantly elevated levels of urinary NGAL and KIM-1 were observed in the fUTI group, as well as with increased urine esterase, serum C reactive protein, and pyuria. The AUC was 72 % for KIM-1 and 96 % for NGAL. The AUC of KIM-1 for the prediction of scarring was 71 % (p < 0.05). CONCLUSIONS: The diagnosis of febrile UTI and the prediction of subsequent scarring may be facilitated by assaying urine biomarkers with acceptable accuracy. PMID- 25127918 TI - Salt intake in children and its consequences on blood pressure. AB - Sodium is the most abundant extracellular cation and therefore pivotal in determining fluid balance. At the beginning of life, a positive sodium balance is needed to grow. Newborns and preterm infants tend to lose sodium via their kidneys and therefore need adequate sodium intake. Among older children and adults, however, excessive salt intake leads to volume expansion and arterial hypertension. Children who are overweight, born preterm, or small for gestational age and African American children are at increased risk of developing high blood pressure due to a high salt intake because they are more likely to be salt sensitive. In the developed world, salt intake is generally above the recommended intake also among children. Although a positive sodium balance is needed for growth during the first year of life, in older children, a sodium-poor diet seems to have the same cardiovascular protective effects as among adults. This is relevant, since: (1) a blood pressure tracking phenomenon was recognized; (2) the development of taste preferences is important during childhood; and (3) salt intake is often associated with the consumption of sugar-sweetened beverages (predisposing children to weight gain). PMID- 25127919 TI - Disturbed skin barrier in children with chronic kidney disease. AB - BACKGROUND: There are limited data on skin lesions in children with end-stage renal failure. The aim of the study was an evaluation of the skin barrier in children with different stages of chronic kidney disease (CKD). The prevalence of xerosis, its severity, as well as its link selected demographic factors, were examined. METHODS: The study included 103 children: 72 with CKD stages 3-5 (38 on conservative treatment and 34 on dialysis) and 31 patients with primary monosymptomatic nocturnal enuresis as a control group. Initially, the study subjects described the localisation and severity of dry skin by themselves. Next, clinical evaluation of xerosis, non-invasive corneometric assessment of epidermis moisturising and the measurement of transepidermal water loss were performed. RESULTS: Most CKD children reported dry skin. The problem of xerosis was identified more frequently in patients on dialysis (67.6 %) than on conservative treatment (42.1 %) (p = 0.01). CKD patients divided according to skin dryness did not differ with regards to age, sex, initial kidney disease and CKD duration. CONCLUSIONS: Disturbed skin barrier is an important concern of children with CKD, intensifying as the disease progresses. This symptom occurs on early stages of CKD and it should be taken into consideration in the CKD management. PMID- 25127920 TI - The paired box transcription factor Pax8 is essential for function and survival of adult thyroid cells. AB - The transcription factor Pax8 is already known to be essential at very early stages of mouse thyroid gland development, before the onset of thyroid hormone production. In this paper we show, using a conditional inactivation strategy, that the removal of the Pax8 protein late in gland development results in severe hypothyroidism, consequent to a reduced gland size and a deranged differentiation. These results demonstrate that Pax8 is also an essential player in controlling survival and differentiation of adult thyroid follicular cells. PMID- 25127916 TI - Best practice guidelines for idiopathic nephrotic syndrome: recommendations versus reality. AB - BACKGROUND: The optimal therapeutic regimen for managing childhood idiopathic nephrotic syndrome (INS) is still under debate. We have evaluated the choice of steroid regimen and of symptomatic treatment adopted by pediatricians and pediatric nephrologists in a large number of centers as the first step towards establishing a shared protocol METHODS: This was a multicenter, retrospective study. A total of 231 children (132 admitted to pediatric units) aged 6 months to <15 years who presented with onset of nephrotic syndrome to 54 pediatric units and six pediatric nephrology units in Italy between 2007 and 2009 were eligible for entry into the study. RESULTS: Median steroid dosing was 55 (range 27-75) mg/m(2)/day. The overall median cumulative dose regimen for the first episode was 3,440 (1,904-6,035) mg/m(2), and the median duration of the therapeutic regimen was 21 (9-48) weeks. The total duration and cumulative steroid dose were significantly higher in patients treated by pediatricians than in those treated by pediatric nephrologists (p = 0.001 and p = 0.008). Among the patient cohort, 55, 64 and 22 % received albumin infusions, diuretics and acetyl salicylic acid treatment, respectively, but the laboratory and clinical data did not differ between children treated or not treated with symptomatic drugs. Albumin and diuretic use did not vary between patients in pediatric units and those in pediatric nephrology units. CONCLUSIONS: This study shows major differences in steroid and symptomatic treatment of nephrotic syndrome by pediatricians and pediatric nephrologists. As these differences can influence the efficacy of the treatments and the appearance of side-effects, shared guidelines and their implementation through widespread educational activities are necessary. PMID- 25127921 TI - Indicators of pulmonary exacerbation in cystic fibrosis: A Delphi survey of patients and health professionals. AB - BACKGROUND: There is uncertainty about the most important indicators of pulmonary exacerbations in CF. METHODS: Two parallel Delphi surveys in 13 CF centres (UK and Ireland). Delphi 1: 31 adults with CF, >= one exacerbation over 12 months. Delphi 2: 38 CF health professionals. Rounds 1 and 2 participants rated their level of agreement with statements relating to indicators of exacerbation; Round 3 participants rated the importance of statements which were subsequently placed in rank order. RESULTS: Objective measurements were of higher importance to health professionals. Feelings of increased debility were rated most important by adults with CF. CONCLUSIONS: There were clear differences in perspectives between the two groups as to the most important indicators of an exacerbation. This highlights that CF health professionals should take more cognisance of specific signs and symptoms reported by adults with CF, especially since these may be a precursor to an exacerbation. PMID- 25127923 TI - Sub-aponeurotic fluid collection in a neonate associated with fetal scalp electrode monitoring: a brief communication. PMID- 25127922 TI - High-frequency audiometry reveals high prevalence of aminoglycoside ototoxicity in children with cystic fibrosis. AB - BACKGROUND: Intravenous aminoglycoside (IV AG) antibiotics, widely used in patients with cystic fibrosis (CF), are known to have ototoxic complications. Despite this, audiological monitoring is not commonly performed and if performed, uses only standard pure-tone audiometry (PTA). The aim of this study was to investigate ototoxicity in CF children, to determine the most appropriate audiological tests and to identify possible risk factors. METHODS: Auditory assessment was performed in CF children using standard pure tone audiometry (PTA), extended high-frequency (EHF) audiometry and distortion-product otoacoustic emissions (DPOAE). RESULTS: 70 CF children, mean (SD) age 10.7 (3.5) years, were recruited. Of the 63 children who received IV AG, 15 (24%) children had ototoxicity detected by EHF audiometry and DPOAE. Standard PTA only detected ototoxicity in 13 children. Eleven of these children had received at least 10 courses of IV AG courses. A 25 to 85 dBHL hearing loss (mean+/-SD: 57.5+/-25.7 dBHL) across all EHF frequencies and a significant drop in DPOAE amplitudes at frequencies 4 to 8 kHz were detected. However, standard PTA detected a significant hearing loss (>20 dBHL) only at 8 kHz in 5 of these 15 children and none in 2 subjects who had significantly elevated EHF thresholds. The number of courses of IV AG received, age and lower lung function were shown to be risk factors for ototoxicity. CONCLUSIONS: CF children who had received at least 10 courses of IV AG had a higher risk of ototoxicity. EHF audiometry identified 2 more children with ototoxicity than standard PTA and depending on facilities available, should be the test of choice for detecting ototoxicity in children with CF receiving IV AG. PMID- 25127924 TI - Immunomodulation of antiretroviral drug-suppressed chronic HIV-1 infection in an oral probiotic double-blind placebo-controlled trial. AB - A putative source of inappropriate immune activation that drives human immunodeficiency virus (HIV)-1 immunopathogenesis is the gastrointestinal tract. Even with effective antiretroviral treatment, residual activation persists. We hypothesized that an oral probiotic could improve the residual immune activation in chronic treated HIV-1 infection, and tested a Bacillus coagulans GBI-30, 6086 capsule probiotic in HIV-1-infected persons with suppressed viremia on stable antiretroviral therapy in a 3-month double-blind placebo-controlled trial (10 probiotic, 7 placebo). The Gastrointestinal Symptom Rating Scale (GSRS) was administered monthly. Blood was tested at the start and end of placebo/probiotic administration for viremia, CD4(+) T cell percentage/concentration, soluble (s)CD14, soluble intestinal fatty acid binding protein, sCD163, D-dimer, C reactive protein (CRP), interleukin-8, and tumor necrosis factor-alpha. All participants maintained viremia <40 RNA copies/ml. The probiotic was safe and well tolerated, and appeared to improve chronic gastrointestinal symptoms. Its administration was associated with a significant increase in the percentage of blood CD4(+) T cells compared to placebo (+2.8% versus -1.8%, p=0.018) although CD4(+) T cell concentrations were generally unchanged in both groups. None of the biomarkers showed significant changes on probiotic treatment or between-group differences in change (although significance was borderline for a greater sCD163 drop in the probiotic versus placebo group, p=0.05). Some biomarkers showed significant correlations to each other, particularly D-dimer with CRP and sCD14 with tumor necrosis factor (TNF)-alpha. These data demonstrate the safety and possible benefit of this probiotic for residual inflammation in treated HIV-1 infection, although further study will be required to determine the immune pathways involved. PMID- 25127925 TI - Riluzole in the prelimbic medial prefrontal cortex attenuates veratrine-induced anxiety-like behaviors in mice. AB - RATIONALE: We previously demonstrated in mice that the activation of prelimbic medial prefrontal cortex (PL) with the sodium channel activator veratrine induces anxiety-like behaviors via NMDA receptor-mediated glutamatergic neurotransmission. Riluzole directly affects the glutamatergic system and has recently been suggested to have an anxiolytic-like effect in both experimental animals and patients with anxiety disorders. OBJECTIVES: We investigated the effects of co-perfusion of riluzole on veratrine-induced anxiety-like behaviors in mice. METHODS: Extracellular glutamate levels were measured in 7-week-old male C57BL6 mice by using an in vivo microdialysis-HPLC/ECD system, and behaviors were assessed simultaneously in an open field (OF) test. Basal levels of glutamate were measured by collecting samples every 10 min for 60 min. The medium containing drugs was perfused for 30 min, and the OF test was performed during the last 10 min of drug perfusion. After the drug treatments, the drug-containing medium was switched to perfusion of control medium lacking drugs, and then samples were collected for another 90 min. RESULTS: Riluzole co-perfusion attenuated veratrine-induced increase in extracellular glutamate levels in the PL and completely diminished veratrine-induced anxiety-like behaviors. Interestingly, riluzole perfusion alone in the PL did not affect the basal levels of glutamate and anxiety-like behaviors. CONCLUSIONS: Our results suggest that compounds like riluzole that inhibit glutamatergic function in the PL are possible candidates for novel anxiolytics. PMID- 25127926 TI - ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval. AB - RATIONALE: Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic glucocorticoid interaction at retrieval, where stress impairs memory, is less understood. OBJECTIVES: We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory. METHODS: This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the alpha2B adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces. RESULTS: A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus. CONCLUSION: The genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval. PMID- 25127928 TI - Predictors of stress and coping strategies of US accelerated vs. generic Baccalaureate Nursing students: an embedded mixed methods study. AB - BACKGROUND: Stress is an inevitable part of life and is especially pervasive in the lives of nursing students. Identifying the predictors of stress as well as coping strategies used can allow for the implementation of appropriate coping interventions to assist in the management of stress in nursing students. Mixed methods research that has been undertaken to gain an understanding about student stress, especially juxtaposing generic versus accelerated nursing students could not be identified. OBJECTIVES: (1) Identify predictors of stress between accelerated and generic Baccalaureate Nursing (BSN) students; and (2) Describe stressors and coping strategies used by accelerated students in comparison with generic students. DESIGN: Embedded mixed methods study. SETTING: Accelerated and generic BSN third- and fourth-year nursing students at two Midwestern universities. PARTICIPANTS: 210 participants: accelerated (n=75) and generic (n=135). METHODS: A questionnaire packet, including demographics, history of depression, the Perceived Stress Questionnaire, Rosenberg Self-Esteem Scale, Multidimensional Scale of Perceived Social Support, and open-ended questions were administered to students at the end of a class. Simultaneous multiple regression was used to examine predictors of stress. Content analysis was used to analyze qualitative data. RESULTS: Predictors of stress for both the accelerated and generic groups included history of depression, year in the program, emotional support, and self-esteem. Fear of failure and clinical incompetence, problematic relationships, and time management issues were identified as major stressors. Coping strategies used by both groups included positive thinking and social support. CONCLUSIONS: Senior students with a history of depression, low self esteem, and little social support were more likely to experience high levels of stress. This gives educators the potential to identify at risk students and establish stress reduction programs. Encouraging students to use individualized coping strategies will be beneficial. PMID- 25127929 TI - Refractive lens exchange. AB - Advances in small incision surgery have enabled cataract surgery to evolve from being concerned primarily with the safe removal of the opaque crystalline lens to a procedure refined to yield the best possible postoperative refractive result. As the outcomes of cataract surgery have improved, the use of lens surgery as a refractive modality in patients without cataracts (clear lens extraction) has increased in popularity. The removal of the crystalline lens for refractive purposes, or so-called refractive lens exchange (RLE), offers distinct advantages over corneal refractive surgery in selected cases. Nevertheless, in some middle aged patients with high refractive errors, corneal refractive surgery can be a safe and effective treatment. In addition, the use of multifocal lenses offers an alternative for the correction of presbyopia. A further advantage of RLE is that it simultaneously eliminates the need for cataract surgery in the future. The keys for success in RLE are effectiveness and consistency in the refractive outcome, providing at the same time surgical and postoperative safety. To achieve these goals, adequate indications following strict risk/benefit criteria and refractive precision based on accurate preoperative protocols for IOL calculation and selection are mandatory, together with an appropriate choice of surgical procedure based on the surgeon's skills, minimizing complications. PMID- 25127927 TI - Moderating effect of working memory capacity on acute alcohol effects on BOLD response during inhibition and error monitoring in male heavy drinkers. AB - RATIONALE: While alcohol intoxication is known to increase disinhibited behavior, the degree to which disinhibition occurs appears to depend on a number of factors including executive functioning ability. However, the neural mechanisms by which individual differences in executive functioning lead to variable degrees of disinhibition remain unclear. OBJECTIVES: The aim of the current study was to examine the neural mechanisms by which individual differences in working memory (WM) capacity moderate alcohol-induced disinhibition. METHODS: Seventeen heavy drinking males participated in a within-subjects design in which two sessions were completed: an alcohol session (.82 g/kg) and a control session. Participants completed a go/no-go task while undergoing functional magnetic resonance imaging (fMRI) after ingestion of the control or alcohol beverage. WM capacity was measured using an operation span task. RESULTS: Significant interactions of session and WM capacity emerged in contrasts examining successful response inhibition within superior temporal gyrus and unsuccessful inhibition in regions within the default mode network. In all cases, individuals with low WM capacity demonstrated a relative decrease in blood oxygen level-dependent (BOLD) response during the alcohol compared to control session, whereas the high-WM-capacity group demonstrated relative increases in BOLD response in the alcohol compared to control session. CONCLUSIONS: Low WM capacity appears to be associated with decreased neural response to signals indicating a need for behavioral control, an effect that may lead to increased difficulty with inhibiting responses and increased negative consequences from alcohol intoxication. PMID- 25127930 TI - Successful nonsurgical endodontic outcome of a severely affected permanent maxillary canine with dens invaginatus Oehlers type 3. AB - INTRODUCTION: The morphogenic complexities of dens invaginatus (DI) Oehlers type 3 in maxillary canines offer significant endodontic challenges. METHODS: A case report is provided of a 14-year-old female patient who presented with an anomalous-looking permanent maxillary canine associated with a sinus tract. Pulp testing revealed a normal response on the distal aspect of the tooth, whereas the mesial segment tested nonresponsive. A radiolucent lesion was seen on the mesiolateral radicular area adjacent to the severely distended pulp chamber. A gutta-percha point inserted into the sinus tract traced to this same region. The diagnosis was normal pulp coincident with DI Oehlers type 3 with pulp necrosis and chronic apical abscess. RESULTS: Despite a concerted effort to limit the root canal therapy to only the necrotic canal, its proximity to the normal canal obviated this possibility, entailing endodontic treatment of the entire root canal system. The necrotic pulp space was subjected to sustained irrigation with 5.25% sodium hypochlorite and then completed with 17% ethylenediaminetetraacetic acid. A bolus of gutta-percha was used to create an apical barrier, and then the remainder of the enlarged pulp space was obturated with injectable thermoplasticized gutta-percha. At a 4.5-year recall, there was no clinical and radiographic evidence of infection. CONCLUSIONS: Endodontic success was accomplished with meticulous efforts of disinfection. Thermoplasticized gutta percha can offer utility for obturation of anatomically complicated pulp spaces. The use of the dental operating microscope is an invaluable aid for discernment of the intricacies of teeth affected with DI type 3 variant and can enhance clinical outcomes. PMID- 25127931 TI - Cell attachment properties of Portland cement-based endodontic materials: biological and methodological considerations. AB - INTRODUCTION: The attachment and spreading of mammalian cells on endodontic biomaterials are an area of active research. The purpose of this review is to discuss the cell attachment properties of Portland cement (PC)-based materials by using scanning electron microscope (SEM). In addition, methodological aspects and technical challenges are discussed. METHODS: A PubMed electronic search was conducted by using appropriate key words to identify the available investigations on the cell attachment properties of PC-based endodontic materials. After retrieving the full text of related articles, the cross citations were also identified. RESULTS: A total of 23 articles published between January 1993 and October 2013 were identified. This review summarizes the cell attachment properties of commercial and experimental PC-based materials on different cell cultures by using SEM. Methodological procedures, technical challenges, and relevance of SEM in determining the biological profile of PC-based materials are discussed. CONCLUSIONS: SEM observations demonstrate that commercial MTA formulations show favorable cell attachment properties, which is consistent with their successful clinical outcomes. The favorable cell attachment properties of PC and its modified formulations support its potential use as a substitute for mineral trioxide aggregate. However, researchers should carefully select cell types for their SEM investigations that would be in contact with the proposed PC based combinations in the clinical situation. Despite being a technical challenge, SEM provides useful information on the cell attachment properties of PC-based materials; however, other assays for cell proliferation and viability are essential to come up with an accurate in vitro biological profile of any given PC-based formulation. PMID- 25127932 TI - Effect of ProTaper Universal, Endoflare, Revo-S, HyFlex coronal flaring instruments, and Gates Glidden drills on crack formation. AB - INTRODUCTION: The aim of the present study was to evaluate crack formation after flaring root canals with Gates Glidden drills and ProTaper Universal (SX; Dentsply Maillefer, Ballaigues, Switzerland), Endoflare (MicroMega, Besancon, France), Revo-S (MicroMega), and HyFlex (Coltene-Whaledent, Allstetten, Switzerland) flaring instruments. METHODS: One-hundred eight mandibular molars were selected. Eighteen teeth were left unprepared to serve as negative controls; the experimental groups consisted of the mesiobuccal and mesiolingual root canals of the remaining 90 teeth, which were instrumented with the following coronal flaring instruments: Gates Glidden drills and ProTaper Universal SX, Endoflare, Revo-S SC1, and HyFlex 25.08 instruments. All roots were then sectioned perpendicular to the long axis at 1, 2, 3, 4, 6, and 8 mm from the cementoenamel junction. The sections were inspected under a stereomicroscope, and any crack formations were recorded. The data were analyzed using the chi-square test (P = .05). RESULTS: The Gates Glidden drills resulted in a higher rate of crack formation than that noted in the control group (P < .05). Flaring of the root canals using the ProTaper Universal, Endoflare, Revo-S, and HyFlex instruments resulted in crack formation similar to that of the control group (P > .05). CONCLUSIONS: The use of the Gates Glidden drills resulted in the formation of the most cracks. However, the results for the ProTaper Universal, Endoflare, Revo-S, and HyFlex flaring instruments were similar to those of the control group in terms of crack formation. PMID- 25127933 TI - Enterococcus faecalis activates caspase-1 leading to increased interleukin-1 beta secretion in macrophages. AB - INTRODUCTION: Recent studies of inflammasome activation have focused on the pathogenesis of diverse inflammatory and autoimmune diseases. Inflammasome activation results in caspase-1 activation, which is required for processing of prointerleukin (IL)-1 beta to its secreted form as well as a proinflammatory cell death (ie, pyroptosis). The purpose of this study was to analyze whether Enterococcus faecalis associated with endodontic infection induces inflammasome activation. METHODS: THP-1 macrophages were treated with E. faecalis in the presence or absence of caspase-1 inhibitors. Caspase-1 activation, pro-IL-1 beta expression, and IL-1 beta secretion were detected by immunoblotting, real-time reverse-transcription polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Cell death was measured by lactate dehydrogenase release and propidium iodide staining. Adenosine triphosphate (ATP) release was measured by an ATP bioluminescence assay kit. RESULTS: E. faecalis induced caspase-1 activation and pro-IL-1 beta expression, which resulted in IL-1 beta secretion in macrophages. E. faecalis significantly induced ATP release, which is a mechanism of Nod-like receptor family protein 3 (NLRP3) inflammasome activation, whereas oxATP treatment inhibited E. faecalis-induced caspase-1 activation. E. faecalis significantly increased lactate dehydrogenase release and propidium iodide uptake, which are characteristics of pyroptosis. CONCLUSIONS: Our results show that E. faecalis may contribute to the progression of pulpal inflammation by stimulating excessive secretion of IL-1 beta and cell death. PMID- 25127934 TI - Evaluation of cone-beam computed tomography in the diagnosis of vertical root fractures: the influence of imaging modes and root canal materials. AB - INTRODUCTION: The purpose of this study was to evaluate the influence of cone beam computed tomography (CBCT) imaging modes in the diagnosis of vertical root fractures with different intracanal materials. METHODS: The sample consisted of 30 single-rooted teeth divided into 3 groups (n = 10), control and complete and incomplete root fracture. In each tooth, different materials were used (gutta percha, metal post, and fiber post) as well as no filling material. Each tooth/root was scanned in a 3D Accuitomo 170 CBCT device by using 4 different imaging modes (high-resolution, high-fidelity, high-speed, and standard). In addition, the dose-area product was calculated for each CBCT imaging mode. The images were randomly evaluated by 5 dentomaxillofacial radiologists. RESULTS: Complete root fractures were visualized more easily than incomplete fractures. The presence of metal post and gutta-percha negatively influenced the diagnosis of root fracture. Regarding the CBCT imaging modes, there was no influence for complete root fracture diagnosis. In cases of incomplete root fractures, high fidelity, high-resolution, and standard had a higher diagnostic accuracy, especially in the fiber post and no filling groups. CONCLUSIONS: The CBCT imaging modes had little influence in the diagnosis of complete and incomplete root fractures, whereas the presence of intracanal material had greater impact on the diagnostic ability, demonstrating that CBCT is not beneficial for the diagnosis of root fractures when metal posts are present. PMID- 25127935 TI - The effect of larger apical preparations in the danger zone of lower molars prepared using the Mtwo and Reciproc systems. AB - INTRODUCTION: The aim of this study was to evaluate the effects of large apical preparations in the danger zones of the mesial root canals of mandibular molars instrumented with the Mtwo and Reciproc systems (VDW, Munich, Germany) until reaching apical diameters of 0.25 and 0.40 mm. METHODS: Twelve mandibular molars, the mesial roots of which presented distinct foramens and similar anatomies, were selected using micro-computed tomographic scanning. Mtwo and Reciproc instruments were used to shape the mesiobuccal or mesiolingual canals. The mesial canals were scanned before and after the use of 0.25- and 0.40-mm Mtwo and Reciproc instruments. The analyzed parameters included the root canal volume and remaining dentin thickness at 5 different levels. The obtained data were subjected to paired analysis of variance and Tukey or Friedman and Dunn tests for intragroup analysis and the Mann-Whitney U test for comparison between the mesial and distal walls. RESULTS: There were no significant differences between the mesial and distal dentin thickness for the points analyzed with both instrumentation techniques (P > .05). The volumetric analysis revealed a significant difference (P < .05) among the initial volume and after the use of the 0.25- and 0.40-mm instruments for both systems. The use of the 0.40-mm instrument increased the root canal volume in comparison to the 0.25-mm instrument (P < .05). CONCLUSIONS: Both systems performed similarly for the preparation of curved root canals with separate apical foramens. The increase of the root canal preparation with the 0.40-mm instrument significantly increased the root canal volume at the apical third without significantly reducing the dentin thickness in the danger zone for both instrument systems. PMID- 25127937 TI - Associations between food consumption habits with meal intake behaviour in Spanish adults. AB - The aim of the present study is to explore the contribution of different types of meal intake behaviour on a healthy diet and seeks to find associations with food consumption habits. A cross-sectional survey with data from 1332 Spanish adults aged between 20 and 79 years was conducted. The survey was carried out during the cardiovascular health event 'Semanas del Corazon 2008' in four Spanish cities. Several food consumption habits such as the recommended intake of fruits, vegetables, milk and dairy products, as well as the regular consumption of fatty and salty food and ready-made meals, were used as dependent variables in logistic regression. We evaluated different meal intake behaviour such as the type of meals, snacking, and drinks taken with a meal. Our survey revealed that snacking is positively associated with the regular consumption of salty and fatty food, and having sugary drinks with meals was positively associated with the regular consumption of ready-made meals. Having a forenoon meal is positively associated with the consumption of two or more portions of milk and dairy products and vegetables, and taking an afternoon meal with the recommended intake of milk and dairy products and fruits. Drinking water during a meal increases the probability of consuming two or more portions of fruits and vegetables. Our results enhance the understanding of the contribution that meal intake behaviour makes to a healthy diet based on food consumption habits. This work provides an insight into eating behaviour and would make a useful contribution to interventions aimed at promoting healthier eating habits. PMID- 25127936 TI - Hydrogen sulfide mitigates hyperglycemic remodeling via liver kinase B1-adenosine monophosphate-activated protein kinase signaling. AB - Hyperglycemia (HG) reduces AMPK activation leading to impaired autophagy and matrix accumulation. Hydrogen sulfide (H2S) treatment improves HG-induced renovascular remodeling however, its mechanism remains unclear. Activation of LKB1 by the formation of heterotrimeric complex with STRAD and MO25 is known to activate AMPK. We hypothesized that in HG; H2S induces autophagy and modulates matrix synthesis through AMPK-dependent LKB1/STRAD/MO25 complex formation. To address this hypothesis, mouse glomerular endothelial cells were treated with normal and high glucose in the absence or presence of sodium hydrogen sulfide (NaHS), an H2S donor. HG decreased the expression of H2S regulating enzymes CBS and CSE, and autophagy markers Atg5, Atg7, Atg3 and LC3B/A ratio. HG increased galectin-3 and periostin, markers of matrix accumulation. Treatment with NaHS to HG cells increased LKB1/STRAD/MO25 formation and AMPK phosphorylation. Silencing the encoded genes confirmed complex formation under normoglycemia. H2S-mediated AMPK activation in HG was associated with upregulation of autophagy and diminished matrix accumulation. We conclude that H2S mitigates adverse remodeling in HG by induction of autophagy and regulation of matrix metabolism through LKB1/STRAD/MO25 dependent pathway. PMID- 25127938 TI - Esophageal diseases. PMID- 25127939 TI - Endoscopy innovations. PMID- 25127940 TI - Endoscopic ultrasound. PMID- 25127941 TI - Endoscopic retrograde cholangiopancreatography. PMID- 25127942 TI - Gastrointestinal bleeding. PMID- 25127943 TI - Capsule endoscopy and deep enteroscopy. PMID- 25127944 TI - Colonoscopy. PMID- 25127945 TI - Colon adenoma surveillance: it takes a program. PMID- 25127946 TI - Colonoscopy preparations: clearing things up. PMID- 25127947 TI - Optical biopsy approaches in Barrett's esophagus with next-generation optical coherence tomography. PMID- 25127948 TI - EUS-guided pancreatic duct rendezvous in a child with traumatic pancreatic duct disruption. PMID- 25127949 TI - Magnetic compression anastomosis through EUS-guided choledochoduodenostomy to repair a disconnected bile duct in orthotopic liver transplantation. PMID- 25127950 TI - Acute duodenal diverticulitis treated with endoscopic therapy. PMID- 25127951 TI - Therapy of rectal carcinoids of 11 to 19 mm: a matter of debate. PMID- 25127952 TI - EUS-guided gold fiducial placement and migration rate. PMID- 25127953 TI - Response:. PMID- 25127954 TI - Repair of esophageal perforations using a novel endoscopic suturing system. PMID- 25127955 TI - Insulated-tip dissecting knife to treat Zenker's diverticulum: is insulation the key? PMID- 25127956 TI - Suction tenting for polypectomy. PMID- 25127957 TI - Set higher adenomas per colonoscopy benchmark. PMID- 25127958 TI - Response:. PMID- 25127959 TI - Premature atherosclerosis, extremely low HDL-cholesterol and concurrent defects in APOA1 and ABCA1 genes: a family case report. PMID- 25127960 TI - Adherence to guidelines and mortality in atrial fibrillation. AB - OBJECTIVE: Determining the adherence to ACC/AHA/ESC 2006 guidelines and its influence on the survival of patients with atrial fibrillation. METHODS: Prospective observational study of patients discharged during 2007 from an Internal Medicine department with a main or secondary diagnose of atrial fibrillation. The stroke risk was estimated with the CHADS2 score. The follow-up was carried out in outpatient medical office or via telephone. RESULTS: We included 259 patients (mean age 80.9 years); 73% of them had a high risk of stroke. Oral anticoagulants were administered to 134 (51.7%), and antiplatelet drugs to 71 (27%) patients. A rate control strategy was chosen for 155 (59.8%) patients and a rhythm control one for 28 (10.8%). In 100 (38.6%) patients, treatment was adherent to the guidelines. Adherence to the guidelines was associated with age (0.95 95%CI 0.92-0.99; p=0.03), contraindication to the use of oral anticoagulants (0.38 95%CI 0.18-0.81; p=0.01) and mitral valve heart disease/valvular prosthesis (2.10 95%CI 1.04-4.25; p=0.04). The median follow-up was 727 days, and 191 patients died. Patients treated according to the guidelines had a higher rate of survival during the first three years (0.47 vs. 0.36; p=0.049). The use of oral anticoagulants was associated with a higher probability of survival over a 5 year period (0.34 vs 0.21; p=0.001) and the rate control strategy during the first year (0.69 vs 0.57; p=0.04). CONCLUSIONS: In the real world, the treatment of atrial fibrillation according to the guidelines is associated with improved survival for up to three years during follow-up. PMID- 25127962 TI - Response to the comment letter about adjustment. PMID- 25127961 TI - The association of asthma and atrial fibrillation--a nationwide population-based nested case-control study. AB - BACKGROUND: Asthma and atrial fibrillation (AF) have been reported to be related to an increased risk of cardiovascular events. However, the relationship between asthma and AF has not been fully elucidated. The purpose of this study was to examine the association between asthma and AF risk. METHODS: We conducted a population-based nested case-control study including a total of 7439 newly diagnosed adult patients with AF and 10,075 age-, gender-, comorbidity-, and cohort entry date-matched subjects without AF from the Taiwan National Health Insurance database. Exposure to asthma as well as medications including bronchodilators and corticosteroid before the index date was evaluated to investigate the association between AF and asthma as well as concurrent medications. RESULTS: AF patients were 1.2 times (adjusted OR 1.2, 95% CI 1.109 1.298) more likely to be associated with a future occurrence of asthma independent of comorbidities and treatment with corticosteroids and bronchodilator. In addition, the risks of new-onset AF were significantly higher among current users of inhaled corticosteroid, oral corticosteroids, and bronchodilators. Newly users (within 6 months) have the highest risk (inhaled corticosteroid: OR, 2.13; 95% CI, 1.226-3.701, P=0.007; oral corticosteroid: OR, 1.932; 95% CI, 1.66-2.25, P<0.001; non-steroid bronchodilator: OR, 2.849; 95% CI, 2.48-3.273, P<0.001). A graded association with AF risk was also observed among subjects treated with corticosteroid (inhaled and systemic administration) and bronchodilators. New users (within 6 months) of these medications had the highest risk of AF (ICS: OR, 2.13; 95% CI, 1.226-3.701, P=0.007; oral corticosteroid: OR, 1.932; 95% CI, 1.66-2.25, P<0.001; non-steroid bronchodilator: OR, 2.849; 95% CI, 2.48-3.273, P<0.001). A graded association with AF risk was also observed among subjects treated with ICS or bronchodilator. CONCLUSIONS: Asthma was associated with an increased risk of developing future AF. PMID- 25127963 TI - Association between chronic obstructive pulmonary disease and tako tsubo cardiomyopathy--a case report. PMID- 25127964 TI - Left ventricular rhabdomyoma in an adult patient: a rare disease successfully treated. PMID- 25127965 TI - Left ventricular outflow tract obstruction as a primary phenotypic expression of hypertrophic cardiomyopathy in mutation carriers without hypertrophy. PMID- 25127966 TI - Excess mortality in women compared to men after PCI in STEMI: an analysis of 11,931 patients during 2000-2009. AB - BACKGROUND: Ambiguity exists whether gender affects outcome in patients undergoing percutaneous coronary intervention (PCI). METHODS: To evaluate the relationship between gender and outcome in a large cohort of PCI patients, 11,931 consecutive patients who underwent PCI for various indications during 2000-2009 were studied using survival analyses and Cox regression models. RESULTS: Most patients (n=8588; 72%) were men. Women were older and more often had a history of hypertension and diabetes mellitus. Men smoked more frequently, had a more extensive cardiovascular history (previous MI, PCI and CABG), a higher prevalence of renal impairment and multi-vessel disease. In STEMI patients, women had higher 31-day mortality rates than men (11.6% vs. 6.5%, respectively, p<0.001). This difference remained after adjustment for confounders (aHR at 30-days 1.54 and 95% CI 1.22-1.96). Likewise, higher mortality was observed at 1-year (15.1% vs. 9.3%) and 4-year follow-up (21.6% vs. 15.0%, aHR 1.30 and 95% CI 1.10-1.53). There were no differences in mortality between women and men in NSTE-ACS (aHR at 4-years 1.05 and 95% CI 0.85-1.28) or stable angina (HR at 4-years 0.85 and 95% CI 0.68 1.08). CONCLUSION: Women undergoing PCI for STEMI had higher mortality than men. The excess mortality in women appeared in the first month after PCI and could only partially be explained by a difference in baseline characteristics. No gender differences in outcome in patients undergoing PCI for NSTE-ACS and stable angina were observed. PMID- 25127967 TI - Sodium tanshinone IIA sulfonate and sodium danshensu open the placental barrier through down-regulation of placental P-glycoprotein in mice: implications in the transplacental digoxin treatment for fetal heart failure. PMID- 25127968 TI - Relationship of subcutaneous fat distributional pattern to blood pressure levels among children and adolescents in Shandong, China. PMID- 25127969 TI - Impact of single versus double vessel carotid disease on long-term survival in patients treated with carotid stenting. PMID- 25127970 TI - Warfarin-related nephropathy: prevalence, risk factors and prognosis. PMID- 25127971 TI - Urban-rural and regional disparities in the prevalence of elevated blood pressure among children and adolescents in Shandong, China. PMID- 25127972 TI - Electrocardiographic findings of secondary arrhythmogenic right ventricular cardiomyopathy in different right ventricular abnormalities: re.: Secondary arrhythmogenic right ventricular cardiomyopathy after decades of operative repair of tetralogy of Fallot. PMID- 25127973 TI - High-sensitivity cardiac troponin for risk prediction in patients with and without coronary heart disease. AB - BACKGROUND: In stable patients with unknown coronary anatomy, higher levels of cardiac troponin are associated with an increased risk of cardiovascular events. It was supposed that this association might be explained by the ability of cardiac troponin to detect minor myocardial necrosis which might be caused by subclinical coronary atherosclerosis. Thus, this analysis tested if the predictive value of high-sensitivity troponin T (hsTnT) in stable patients is dependent of the presence or absence of angiographically documented coronary heart disease. METHODS: Stable patients undergoing elective coronary angiography were enrolled (n=2046). HsTnT was determined before diagnostic procedures. The patients were followed for up to seven years. Primary endpoint was all-cause mortality or non-fatal myocardial infarction. All endpoints were adjudicated by independent physicians. Results were adjusted to a clinical model including independent clinical predictors of the primary endpoint. RESULTS: Out of the 2046 patients enrolled, 1236 (60%) had a diagnosis of obstructive coronary heart disease. HsTnT predicted independently the primary endpoint (adjusted HR 1.33, 95%-CI 1.21-1.46, P<0.001). The use of hsTnT in addition to the clinical model significantly improved discrimination (c-statistic: 0.751 to 0.773, P<0.001) as well as reclassification of the primary endpoint (NRI=0.362, P<0.001). This significant improvement persisted across various subsets and was independent of the presence of clinically detectable coronary heart disease and other variables. CONCLUSION: The use of hsTnT in addition to clinical variables significantly improves discrimination and reclassification of patients with respect to all cause mortality or non-fatal myocardial infarction irrespective of the presence of clinically detectable coronary heart disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT00457236). PMID- 25127974 TI - Intramyocellular lipid is increased in the skeletal muscle of patients with dilated cardiomyopathy with lowered exercise capacity. PMID- 25127975 TI - Amplatzer vascular plug for patent ductus arteriosus migrated to pulmonary artery six months after closure in a 59 year old female. PMID- 25127976 TI - Prolonged effectiveness of coronary artery bypass surgery versus drug-eluting stents in diabetics with multi-vessel disease: an updated systematic review and meta-analysis. AB - BACKGROUND: Currently, the appropriateness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES) versus coronary artery bypass grafting (CABG) for patients with diabetes (DM) and multi-vessel disease (MVD) is uncertain due to limited evidence from few randomised controlled trials (RCTs). We aimed to compare the clinical effectiveness of CABG versus PCI-DES in DM-MVD patients using an evidence-based approach. METHODS: A systematic review and meta analyses were conducted to compare the risk of all-cause mortality, myocardial infarction (MI), repeat revascularisation, cerebrovascular events (CVE), and major adverse cardiac or cerebrovascular events (MACCE). RESULTS: A total of 1,837 and 3,052 DM-MVD patients were pooled from four RCTs (FREEDOM, SYNTAX, VA CARDS, and CARDia) and five non-randomised studies. At mean follow-up of 3 years, CABG compared with PCI-DES was associated with a lower risk of all-cause mortality and MI in RCTs. By contrast, no significant differences were observed in the mean 3.5-year risk of all-cause mortality and MI in non-randomised trials. However, the risk of repeat revascularisations following PCI-DES compared with CABG was 2.3 (95% CI=1.8-2.8) and 3.0 (2.3-4.2)-folds higher in RCTs and non randomised trials, respectively. Accordingly, the risk of MACCE at 3 years following CABG compared with PCI-DES was lower in both RCTs and non-randomised trials [0.65 (: 0.55-0.77); and 0.77 (0.60-0.98), respectively]. CONCLUSIONS: Based on our pooled results, we recommend CABG compared with PCI-DES for patients with DM-MVD. Although non-randomised trials suggest no additional survival-, MI-, and CVE- benefit from CABG over PCI-DES, these results should be interpreted with care. PMID- 25127977 TI - Effect of repeat twice daily sessions of remote ischemic conditioning over the course of one week on blood pressure of a normotensive/prehypertensive subject. PMID- 25127978 TI - Acute coronary syndrome and coronary intervention in a patient with type 2M von Willebrand disease. PMID- 25127979 TI - Aborted sudden cardiac death due to intractable ventricular fibrillation caused by coronary spasm refractory to implantable cardioverter defibrillator therapy. PMID- 25127980 TI - Chronic constrictive pericarditis in general adult population. PMID- 25127981 TI - Retracted: Significant variations in afferent conduction and axonal morphology of aortic depressive nerve imply broader spectrum of baroreflex function of myelinated Ah-type baroreceptor neurons in female rats. PMID- 25127982 TI - Active coping toward predatory stress is associated with lower corticosterone and progesterone plasma levels and decreased methylation in the medial amygdala vasopressin system. AB - An active coping style displayed under stress - which involves proactive investigatory responses toward environmental threats - has been associated with reduced vulnerability to psychiatric illness. However, the neurobiological determinants of coping styles are not well understood. When rats are exposed to a naturalistic stressor (cat fur) in a group, some individuals in the group show robust active investigation of the stimulus while others show a passive response involving retreat, immobility and close aggregation with conspecifics. Here we explored endocrine and epigenetic correlates of these contrasting coping styles. Male Wistar rats (n=48) were exposed to cat fur in groups of 4 and the passive and active responders were identified and assessed for endocrine and epigenetic differences. Three days after the final cat fur exposure, active responders had substantially lower plasma levels of corticosterone and progesterone than passive responders. Plasma and testicular testosterone levels did not differ between active and passive responders. Active responders had markedly less methylation of the AVP CGCG promoter region located at base 4970 in the posterodorsal region of the medial amygdala but did not differ in the methylation status of the CCGG sequence located at base 2243. This is in agreement with prior research suggesting that AVP and progesterone act in opposition within the medial amygdala to modulate stress-related behaviors. The present study reports striking endocrine and epigenetic differences between active and passive responders, providing insight into potential systems involved in the manifestation of differing coping styles. PMID- 25127983 TI - Endurance training minimizes age-related changes of left ventricular twist untwist mechanics. AB - BACKGROUND: The aim of this study was to test the effect of endurance training on the age-related changes of left ventricular (LV) twist-untwist mechanics. Aging has been shown to induce a decline of diastolic function and more recently an impairment of twist-untwist mechanics, which constitutes an important factor for early diastolic suction and filling. On the other hand, endurance training has been shown to improve cardiac function. METHODS: Speckle-tracking echocardiography was performed in 106 endurance-trained male athletes and 75 controls (age range 18-70 years), divided into three groups according to age. RESULTS: From the younger to older age groups, progressive increases in LV apical rotation and twist angle and a decrease in LV untwisting rate during isovolumic relaxation time were observed. Athletes had lower systolic twist angles (P < .01) but higher untwist/twist ratios and LV untwisting rate during isovolumic relaxation time compared with controls, with the largest difference between senior groups (51 +/- 24% vs 42 +/- 22% in the young and 42 +/- 29% vs 24 +/- 25% in seniors, P < .001, respectively). The normal timing of untwisting rate occurring before radial displacement was preserved in athletes with increasing age, whereas it was blunted in controls. CONCLUSIONS: Endurance training does not prevent but minimizes changes in LV twist-untwist mechanics from young subjects to seniors. Athletes showed smaller increases of twist angle with age and smaller declines of LV untwisting rate during isovolumic relaxation time and untwist/twist ratio compared with controls. This training-improved preservation of LV twist-untwist mechanics is likely to play a key role for systolic-diastolic coupling and diastolic filling, particularly during exercise. PMID- 25127984 TI - Effect of gadolinium injection on diffusion-weighted imaging with background body signal suppression (DWIBS) imaging of breast lesions. AB - OBJECTIVES: Diffusion-weighted imaging with background body signal suppression (DWIBS) provides both qualitative and quantitative imaging of breast lesions and are usually performed before contrast material injection (CMI). This study aims to assess whether the administration of gadolinium significantly affects DWIBS imaging. METHODS: 200 patients were prospectively evaluated by MRI with STIR, TSE T2, pre-CMI DWIBS, contrast enhanced THRIVE-T1 and post-CMI DWIBS sequences. Pre and post-CMI DWIBS were analyzed searching for the presence of breast lesions and calculating the ADC value. ADC values of <=1.44*10(-3) mm(2)/s were considered suspicious for malignancy. This analysis was then compared with the histological findings. Sensitivity, specificity, diagnostic accuracy (DA), positive predictive value (PPV) and negative (NPV) were calculated for both sequences and represented by ROC analysis. Pre and post-CMI ADC values were compared by using the paired t test. RESULTS: In 150/200 (59%) patients, pre and post-CMI DWIBS indicated the presence of breast lesions, 53 (35%) with ADC values of >1.44*10(-3) mm(2)/s and 97 (65%) with ADC<=1.44*10(-3) mm(2)/s. Pre-CMI and post-DWIBS sequences obtained the same sensitivity, specificity, DA, PPV and NPV values of 97%, 83%, 89%, 79% and 98%. The mean ADC value of benign lesions was 1.831+/-0.18*10(-3) mm(2)/s before and 1.828+/-0.18*10(-3) mm(2)/s after CMI. The mean ADC value of the malignant lesions was 1.146+/-0.16*10(-3) mm(2)/s before and 1.144+/-0.16*10(-3) mm(2)/s after CMI. No significant difference was found between pre and post CMI ADC values (p>0.05). CONCLUSION: DWIBS imaging is not influenced by CMI. Breast MR protocol could be modified by placing DWIBS after dynamic contrast enhanced sequences in order to maximize patient cooperation. PMID- 25127985 TI - [Pulmonary hypertension: definition, diagnostic and new classification]. AB - Pulmonary hypertension (PH): mean pulmonary arterial pressure (mPAP) >= 25 mm Hg on right heart catheterization at rest. Pulmonary arterial hypertension (PAH): mPAP >= 25 mm Hg, pulmonary capillary wedge pressure (PCWP) <= 15 mm Hg and pulmonary vascular resistances (PVR) >3 Wood units. Patients with compatible symptoms (exertional dyspnea, syncopes, signes of right heart failure) can show signs of PH on cardiac echography and therefore need to be investigated in search of the cause of PH. After ruling out the frequent causes of PH (left heart and chronic respiratory diseases), the V/Q lung scan is used to screen for patients with post-embolic PH, that need to be further investigated hemodynamically and radiologically in order to decide operability. For the rest of the patients, only right heart catheterization can identify patients with precapillary PH and these patients must be further evaluated (clinically, by blood samples and by imaging techniques) in order to be classified in one the PH groups of the classification. For the future the discovery of novel risk factors and understanding the mechanism involved with the already known ones represent two major points of research. PMID- 25127986 TI - Accuracy of colposcopy in HIV seropositive and seronegative women with abnormal Pap tests. AB - OBJECTIVE: The aim of this study is to compare colposcopic findings and the accuracy of colposcopic impression in HIV seropositive and seronegative women with abnormal Pap tests. METHODS: HIV seropositive and seronegative women in a national cohort study had Pap tests collected every six months, with colposcopy for any abnormal result. Prospectively collected colposcopy and histology findings were analyzed retrospectively using Pearson Chi-square, t-test and Wilcoxon two-sample tests, logistic regression models, and Kappa coefficients. RESULTS: After adjusting for age and Pap result, 1618 eligible HIV seropositive women were more likely than 406 seronegative women to have inadequate colposcopic examinations, abnormal colposcopic findings, and large cervical lesions. However, among those with abnormal colposcopy, colposcopic characteristics and lesion size and number did not differ by HIV serostatus. Agreement between colposcopists' impressions and highest grade biopsy diagnoses was fair (kappa coefficient 0.35, 95% C.I. 0.31, 0.38). Agreement did not differ by HIV serostatus and did not improve with multiple biopsies (weighted kappa coefficient 0.35, 95% C.I. 0.32, 0.39) or after including all histology results over two years following colposcopy. CONCLUSION: Although HIV seropositive women with abnormal cytology are more likely to have colposcopic abnormality, the performance of colposcopy appears to be similar to that in HIV seronegative women. Biopsy is required to confirm colposcopic impression. PMID- 25127987 TI - Polymorphisms in immune mediators associate with risk of cervical cancer. AB - OBJECTIVE: The immune system is critical for controlling the progression of HPV cervical disease and the development of cancer. This study aimed to identify cervical cancer susceptibility alleles in candidate immune-modulating genes. METHODS: Our family-based study involved a cohort of 641 probands (women with ICC/CIN III) and their biologic parents or siblings (641 trios). In the discovery phase (stage 1), involving 288 of the trios, 80 tag single nucleotide polymorphisms (SNPs) in 11 immune-modulating genes (IFNG, IFNGR1, IFNGR2, JAK1, JAK2, STAT1, STAT6, IL12A, TNF, LTA and LTB) were evaluated on the GoldenGate platform. We used the combined dataset for a total of 641 trios (stage 2) and the Taqman platform to validate the SNPs that had proved significant in the discovery dataset. The transmission disequilibrium test was used to detect significant shifts in allelic transmissions in the datasets. RESULTS: Two SNPs in JAK2 and one SNP in STAT6 showed significant allelic association with cervical cancer in the stage 1 discovery dataset and were replicated in the larger joint analysis stage 2 dataset (JAK2 rs10815144, P=0.0029 and rs12349785, P=0.0058; and STAT6 rs3024971, P=0.0127). An additional SNP in exon 19 of JAK2 (rs2230724) was also examined in the combined dataset due to its strong linkage disequilibrium (LD) with rs10815144. It was also significant (P=0.0335). CONCLUSIONS: Our results suggest an association of SNPs in JAK2 and STAT6 with cervical cancer. This association should be investigated in additional cervical cancer populations. PMID- 25127988 TI - Abnormal CA-125 levels in menopausal women without ovarian cancer. AB - OBJECTIVE: To determine if an abnormal CA-125 level in a menopausal female without ovarian cancer is associated with an increase in mortality. METHODS: The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Randomized Controlled (PLCO) Trial is a large multicenter prospective trial conducted by the National Cancer Institute (NCI). Over 78,000 healthy women aged 55-74 were randomized to a screening arm versus a usual medical care arm to evaluate the efficacy of screening in reducing mortality due to ovarian cancer. Women in the screening arm underwent annual screening for ovarian cancer with transvaginal ultrasound and CA 125 levels. There were 38,818 patients without ovarian cancer that had at least one CA-125 level drawn; 1201 (3.09%) had at least one abnormal level. The current study compares mortality in patients that had one or more abnormal CA-125 levels without ovarian cancer versus those with all normal levels. RESULTS: Patients with one or more abnormal CA-125 levels, without ovarian cancer, had a significantly higher mortality than patients with all normal CA-125 levels in the PLCO screening trial (p<0.0001). This increased risk extended throughout the follow-up period. Analysis of cause of death listed on the death certificate showed an excess mortality attributable to lung cancer, digestive disease, and endocrine, nutritional, and metabolic disease. CONCLUSION: Menopausal females with an elevated CA-125 and without ovarian cancer are exposed to an increased risk of premature mortality. PMID- 25127989 TI - Formulation and photoirradiation parameters that influenced photoresponsive drug delivery using alkoxylphenacyl-based polycarbonates. AB - Recently, we reported the synthesis and biocompatibility of alkoxylphenacyl-based polycarbonates (APP); a promising new class of polymers that undergo photo induced chain scission. In the current study, nanoparticles (NPs) were prepared from the APP polymer (APP-NPs) and loaded with doxorubicin (DOX) (DOX-APP-NPs) in order to identify and evaluate formulation and photoirradiation parameters that influence photoresponsive efficacy. Stable and spherical APP-NPs were prepared with diameters between 70-80nm depending on APP concentration (10-40mg/mL). There was a direct relationship between APP concentration and resultant particle size. Drug release studies indicated that exposure to the photo-trigger was capable of altering the rate and extent of DOX released. Photoresponsive DOX release was markedly influenced by the frequency of photoirradiation while the effect of APP concentration was most likely propagated through NP size. DOX released by photoactivation retained its efficacy as assessed by cytotoxicity studies in human lung adenocarcinoma (A549) cells. Studies in BALB/c mice indicated that DOX APP-NPs induce less cardiotoxicity than DOX alone and that DOX-APP-NPs are not susceptible to dose dumping after photoirradiation. PMID- 25127990 TI - Congenital myopathies with secondary neuromuscular transmission defects; a case report and review of the literature. AB - Congenital myopathies are a clinically and genetically heterogeneous group of disorders characterized by early onset hypotonia, weakness and characteristic, but not pathognomonic, structural abnormalities in muscle fibres. The clinical features overlap with muscular dystrophies, myofibrillar myopathies, neurogenic conditions and congenital myasthenic syndromes. We describe a case of cap myopathy with myasthenic features due to a mutation in the TPM2 gene that responded to anticholinesterase therapy. We also review other published cases of congenital myopathies with neuromuscular transmission abnormalities. This report expands the spectrum of congenital myopathies with secondary neuromuscular transmission defects. The recognition of these cases is important since these conditions can benefit from treatment with drugs enhancing neuromuscular transmission. PMID- 25127991 TI - FAK is required for tension-dependent organization of collective cell movements in Xenopus mesendoderm. AB - Collective cell movements are integral to biological processes such as embryonic development and wound healing and also have a prominent role in some metastatic cancers. In migrating Xenopus mesendoderm, traction forces are generated by cells through integrin-based adhesions and tension transmitted across cadherin adhesions. This is accompanied by assembly of a mechanoresponsive cadherin adhesion complex containing keratin intermediate filaments and the catenin-family member plakoglobin. We demonstrate that focal adhesion kinase (FAK), a major component of integrin adhesion complexes, is required for normal morphogenesis at gastrulation, closure of the anterior neural tube, axial elongation and somitogenesis. Depletion of zygotically expressed FAK results in disruption of mesendoderm tissue polarity similar to that observed when expression of keratin or plakoglobin is inhibited. Both individual and collective migrations of mesendoderm cells from FAK depleted embryos are slowed, cell protrusions are disordered, and cell spreading and traction forces are decreased. Additionally, keratin filaments fail to organize at the rear of cells in the tissue and association of plakoglobin with cadherin is diminished. These findings suggest that FAK is required for the tension-dependent assembly of the cadherin adhesion complex that guides collective mesendoderm migration, perhaps by modulating the dynamic balance of substrate traction forces and cell cohesion needed to establish cell polarity. PMID- 25127992 TI - The Fog signaling pathway: insights into signaling in morphogenesis. AB - Epithelia form the building blocks of many tissue and organ types. Epithelial cells often form a contiguous 2-dimensional sheet that is held together by strong adhesions. The mechanical properties conferred by these adhesions allow the cells to undergo dramatic three-dimensional morphogenetic movements while maintaining cell-cell contacts during embryogenesis and post-embryonic development. The Drosophila Folded gastrulation pathway triggers epithelial cell shape changes that drive gastrulation and tissue folding and is one of the most extensively studied examples of epithelial morphogenesis. This pathway has yielded key insights into the signaling mechanisms and cellular machinery involved in epithelial remodeling. In this review, we discuss principles of morphogenesis and signaling that have been discovered through genetic and cell biological examination of this pathway. We also consider various regulatory mechanisms and the system's relevance to mammalian development. We propose future directions that will continue to broaden our knowledge of morphogenesis across taxa. PMID- 25127993 TI - Retinoic acid plays an evolutionarily conserved and biphasic role in pancreas development. AB - As the developing zebrafish pancreas matures, hormone-producing endocrine cells differentiate from pancreatic Notch-responsive cells (PNCs) that reside within the ducts. These new endocrine cells form small clusters known as secondary (2 degrees ) islets. We use the formation of 2 degrees islets in the pancreatic tail of the larval zebrafish as a model of beta-cell neogenesis. Pharmacological inhibition of Notch signaling leads to precocious endocrine differentiation and the early appearance of 2 degrees islets in the tail of the pancreas. Following a chemical screen, we discovered that blocking the retinoic acid (RA)-signaling pathway also leads to the induction of 2 degrees islets. Conversely, the addition of exogenous RA blocks the differentiation caused by Notch inhibition. In this report we characterize the interaction of these two pathways. We first verified that signaling via both RA and Notch ligands act together to regulate pancreatic progenitor differentiation. We produced a transgenic RA reporter, which demonstrated that PNCs directly respond to RA signaling through the canonical transcriptional pathway. Next, using a genetic lineage tracing approach, we demonstrated these progenitors produce endocrine cells following inhibition of RA signaling. Lastly, inhibition of RA signaling using a cell-type specific inducible cre/lox system revealed that RA signaling acts cell autonomously in PNCs to regulate their differentiation. Importantly, the action of RA inhibition on endocrine formation is evolutionarily conserved, as shown by the differentiation of human embryonic stem cells in a model of human pancreas development. Together, these results revealed a biphasic function for RA in pancreatogenesis. As previously shown by others, RA initially plays an essential role during embryogenesis as it patterns the endoderm and specifies the pancreatic field. We reveal here that later in development RA is involved in negatively regulating the further differentiation of pancreatic progenitors and expands upon the developmental mechanisms by which this occurs. PMID- 25127994 TI - Sterol carrier protein 2 regulates proximal tubule size in the Xenopus pronephric kidney by modulating lipid rafts. AB - The kidney is a homeostatic organ required for waste excretion and reabsorption of water, salts and other macromolecules. To this end, a complex series of developmental steps ensures the formation of a correctly patterned and properly proportioned organ. While previous studies have mainly focused on the individual signaling pathways, the formation of higher order receptor complexes in lipid rafts is an equally important aspect. These membrane platforms are characterized by differences in local lipid and protein compositions. Indeed, the cells in the Xenopus pronephric kidney were positive for the lipid raft markers ganglioside GM1 and Caveolin-1. To specifically interfere with lipid raft function in vivo, we focused on the Sterol Carrier Protein 2 (scp2), a multifunctional protein that is an important player in remodeling lipid raft composition. In Xenopus, scp2 mRNA was strongly expressed in differentiated epithelial structures of the pronephric kidney. Knockdown of scp2 did not interfere with the patterning of the kidney along its proximo-distal axis, but dramatically decreased the size of the kidney, in particular the proximal tubules. This phenotype was accompanied by a reduction of lipid rafts, but was independent of the peroxisomal or transcriptional activities of scp2. Finally, disrupting lipid micro-domains by inhibiting cholesterol synthesis using Mevinolin phenocopied the defects seen in scp2 morphants. Together these data underscore the importance for localized signaling platforms in the proper formation of the Xenopus kidney. PMID- 25127996 TI - Report of the National Institutes of Health task force on research standards for chronic low back pain. AB - OBJECTIVES: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed nonspecific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. The purpose of this article is to disseminate the report of the National Institutes of Health (NIH) task force on research standards for cLBP. METHODS: The NIH Pain Consortium charged a research task force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. RESULTS: The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the Patient Reported Outcomes Measurement Information System methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved these recommendations, which investigators should incorporate into NIH grant proposals. CONCLUSIONS: The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of cLBP. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will become a dynamic document and undergo continual improvement. PMID- 25127997 TI - Development of a neck pain risk score for predicting nonspecific neck pain with disability in office workers: a 1-year prospective cohort study. AB - OBJECTIVE: The purpose of this study was to develop a neck pain risk score for office workers (NROW) to identify office workers at risk for developing nonspecific neck pain with disability. METHODS: A 1-year prospective cohort study of 559 healthy office workers was conducted. At baseline, risk factors were assessed using questionnaires and standardized physical examination. The incidence of neck pain was collected every month thereafter. Disability level was evaluated using the neck disability index. Logistic regression was used to select significant factors to build a risk score. The coefficients from the logistic regression model were transformed into the components of a risk score. RESULTS: Among 535 (96%) participants who were followed up for 1 year, 23% reported incident neck pain with disability (>=5). After adjusting for confounders, the onset of neck pain with disability was significantly associated with history of neck pain, chair adjustability, and perceived muscular tension. Thus, the NROW comprises 3 questions about history of neck pain, chair adjustability, and perceived muscular tension. The NROW had scores ranging from 0 to 4. A cut-off score of at least 2 had a sensitivity of 82% and specificity of 48%. The positive and negative predictive values were 29% and 91%, respectively. The area under the receiver operating characteristic curve was 0.75. CONCLUSION: The risk score for nonspecific neck pain with disability in office workers was developed, and it contained 3 items with scores ranging from 0 to 4. This study shows that the score appears to have reasonable sensitivity, specificity, positive predictive value, and negative predictive values for the cut-off point of at least 2. PMID- 25127998 TI - Can functional capacity tests predict future work capacity in patients with whiplash-associated disorders? AB - OBJECTIVE: To determine whether functional capacity evaluation (FCE) tests predict future work capacity (WC) of patients with whiplash-associated disorders (WADs) grades I and II who did not regain full WC 6 to 12 weeks after injury. DESIGN: Prospective cohort study. SETTING: Rehabilitation center. PARTICIPANTS: Workers (N=267) listed on workers' compensation with grade I or II WADs 6 to 12 weeks after injury. INTERVENTIONS: Patients performed 8 work-related FCE tests. MAIN OUTCOME MEASURES: WC (0-100%) measured at baseline and 1, 3, 6, and 12 months after testing. Correlation coefficients between FCE tests and WC were calculated. A linear mixed-model analysis was used to assess the association between FCE and future WC. RESULTS: Mean +/- SD WC increased over time from 20.8%+/-27.6% at baseline to 32.3%+/-38.4%, 51.3%+/-42.8%, 65.6%+/-42.2%, and 83.2%+/-35.0% at the 1-, 3-, 6-, and 12-month follow-ups, respectively. Correlation coefficients between FCE tests and WC ranged from r=.06 (lifting low at 12-mo follow-up) to r=.39 (walking speed at 3mo). Strength of the correlations decreased over time. FCE tests did not predict WC at follow-up. The predictors of WC were ln (time) (beta=23.74), mother language (beta=5.49), WC at baseline (beta=1.01), and self-reported disability (beta=-.20). Two interaction terms, ln (time) * WC (beta=-.19) and ln (time) * self-reported disability (beta=-.21), were significant predictors of WC. CONCLUSIONS: FCE tests performed within 6 to 12 weeks after WADs injury grades I and II are associated with WC at baseline but do not predict future WC, whereas time course, mother language, WC at baseline, and self-reported disability do predict future WC. Additionally, the interaction between time course WC at baseline and self-reported disability predicted future WC. PMID- 25127995 TI - In vivo analysis of hyaloid vasculature morphogenesis in zebrafish: A role for the lens in maturation and maintenance of the hyaloid. AB - Two vascular networks nourish the embryonic eye as it develops - the hyaloid vasculature, located at the anterior of the eye between the retina and lens, and the choroidal vasculature, located at the posterior of the eye, surrounding the optic cup. Little is known about hyaloid development and morphogenesis, however. To begin to identify the morphogenetic underpinnings of hyaloid formation, we utilized in vivo time-lapse confocal imaging to characterize morphogenesis of the zebrafish hyaloid through 5 days post fertilization (dpf). Our data segregate hyaloid formation into three distinct morphogenetic stages: Stage I: arrival of hyaloid cells at the lens and formation of the hyaloid loop; Stage II: formation of a branched hyaloid network; Stage III: refinement of the hyaloid network. Utilizing fixed and dissected tissues, distinct Stage II and Stage III aspects of hyaloid formation were quantified over time. Combining in vivo imaging with microangiography, we demonstrate that the hyaloid system becomes fully enclosed by 5dpf. To begin to identify the molecular and cellular mechanisms underlying hyaloid morphogenesis, we identified a recessive mutation in the mab21l2 gene, and in a subset of mab21l2 mutants the lens does not form. Utilizing these "lens less" mutants, we determined whether the lens was required for hyaloid morphogenesis. Our data demonstrate that the lens is not required for Stage I of hyaloid formation; however, Stages II and III of hyaloid formation are disrupted in the absence of a lens, supporting a role for the lens in hyaloid maturation and maintenance. Taken together, this study provides a foundation on which the cellular, molecular and embryologic mechanisms underlying hyaloid morphogenesis can be elucidated. PMID- 25128000 TI - Effects of an anterior ankle-foot orthosis on walking mobility in stroke patients: get up and go and stair walking. AB - OBJECTIVE: To examine the effects of an anterior ankle-foot orthosis (AAFO) on walking mobility in stroke patients. DESIGN: Cross-sectional and repeated measures study design. SETTING: A university's neurologic rehabilitation department. PARTICIPANTS: Ambulant stroke patients (N=21). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Walking mobility was measured by the Timed Up and Go (TUG) test and the Timed Up and Down Stairs (TUDS) test. The paired t test was used to determine the difference between the mobility performances measured with and without the AAFO. RESULTS: There were significant differences between mobility performances with and without an AAFO in the TUG test (P=.038) and the TUDS test (P=.000). CONCLUSIONS: This study supports the effect of an AAFO on walking mobility in stroke patients. The findings demonstrate that stroke patients wearing an AAFO may ambulate with greater speed and safety on level surfaces and stairs. PMID- 25127999 TI - Carpal tunnel syndrome: hand surgeons, hand therapists, and physical medicine and rehabilitation physicians agree on a multidisciplinary treatment guideline results from the European HANDGUIDE Study. AB - OBJECTIVE: To achieve consensus on a multidisciplinary treatment guideline for carpal tunnel syndrome (CTS). DESIGN: Delphi consensus strategy. SETTING: Systematic reviews reporting on the effectiveness of surgical and nonsurgical interventions were conducted and used as an evidence-based starting point for a European Delphi consensus strategy. PARTICIPANTS: In total, 35 experts (hand surgeons selected from the Federation of European Societies for Surgery of the Hand, hand therapists selected from the European Federation of Societies for Hand Therapy, physical medicine and rehabilitation physicians) participated in the Delphi consensus strategy. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Each Delphi round consisted of a questionnaire, analysis, and feedback report. RESULTS: After 3 Delphi rounds, consensus was achieved on the description, symptoms, and diagnosis of CTS. The experts agreed that patients with CTS should always be instructed, and instructions combined with splinting, corticosteroid injection, corticosteroid injections plus splinting, and surgery are suitable treatments for CTS. Relevant details for the use of instructions, splinting, corticosteroid injections, and surgery were described. Main factors for selecting one of the aforementioned treatment options were identified as follows: severity and duration of the disorder and previous treatments received. A relation between the severity/duration and choice of therapy was found by the experts and reported in the guideline. CONCLUSIONS: This multidisciplinary treatment guideline may help physicians and allied health care professionals to provide patients with CTS with the most effective and efficient treatment available. PMID- 25128001 TI - Polymorphisms in estrogen receptors predict the risk of male infertility: a meta analysis. AB - BACKGROUND: Estrogen receptors play an important role in mediating estrogen action on target tissues, and the estrogen is relevant to male infertility. Single nucleotide polymorphisms (SNPs) in estrogen receptors may be associated with the risk of male infertility. A variety of case control studies have been published evaluating this association. However, the accumulated studies have shown inconsistent conclusions. METHODS: To further determine the potential association between the four common SNPs (rs2234693, rs9340799, rs1256049 and rs4986938) in estrogen receptors gene and male infertility, this meta-analysis was performed according to the 10 published case control studies. The odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the strength of the associations. RESULTS: It was revealed that the sub-group analysis by the ethnicity, for the rs2234693, a significant association in the comparison of CC vs. TT (OR = 0.61, 95% CI: 0.40-0.93), CT vs. TT (OR = 0.67, 95% CI: 0.49-0.93) and CC + CT vs. TT (OR = 0.66, 95% CI: 0.49-0.89) in the Asian population with male infertility. For rs9340799 polymorphism, increased risks were observed for the comparison of AA vs. GG (OR = 1.75, 95% CI: 1.15-2.68) and AA vs. GA + GG (OR = 1.38, 95% CI: 1.02-1.88). For rs1256049 polymorphism, the comparison of the GA vs. GG (OR = 1.52, 95% CI: 1.00-2.31) and AA + GA vs. GG (OR = 1.74, 95% CI: 1.03 2.94), also increased risks present in Asian and Caucasian population, respectively. CONCLUSIONS: The rs2234693C allele was associated with the decreased risk for male infertility; however, the rs9340799AA genotype and the rs1256049GA genotype were associated with an increased risk for male infertility. PMID- 25128002 TI - Effect of electroacupuncture versus pelvic floor muscle training plus solifenacin for moderate and severe mixed urinary incontinence in women: a study protocol. AB - BACKGROUND: In women with mixed urinary incontinence, pelvic floor muscle training and solifenacin is the recommended conservative treatment, while electroacupuncture is a safe, economical and effective option. METHODS/DESIGN: In this prospective, multi-center, randomized controlled trial, five hundred women with mixed urinary incontinence, from 10 centers will be randomized to receive either electroacupuncture or pelvic floor muscle training plus solifenacin. Women in the acupuncture group will receive electroacupuncture for 3 sessions per week, over 12 weeks, while women in the control group will receive pelvic floor muscle training plus solifenacin (5 mg once daily) for 36 weeks. The primary outcome measure is the proportion of change in 72-hour incontinence episode frequency from baseline to week 12. The secondary outcome measures include eleven items, including proportion of participants with >=50% decrease in average 72-h incontinence episode frequency, change from baseline in the amount of urine leakage and proportion of change from baseline in 72-h incontinence episode frequency in week 25-36, and so forth. Statistical analysis will include covariance analysis, nonparametric tests and t tests. DISCUSSION: The objective of this trial is to compare the efficacy and safety of electroacupuncture versus pelvic floor muscle training plus solifenacin in women with moderate and severe mixed urinary incontinence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02047032. PMID- 25128004 TI - Relating therapy for voices (the R2V study): study protocol for a pilot randomized controlled trial. AB - BACKGROUND: Evidence exists for the effectiveness of cognitive behaviour therapy for psychosis with moderate effect sizes, but the evidence for cognitive behaviour therapy specifically for distressing voices is less convincing. An alternative symptom-based approach may be warranted and a body of literature has explored distressing voices from an interpersonal perspective. This literature has informed the development of relating therapy and findings from a case series suggested that this intervention was acceptable to hearers and therapists. METHODS/DESIGN: An external pilot randomized controlled trial (RCT) comparing outcomes for 15 patients receiving 16 hours (weekly sessions of one hour) of relating therapy and their usual treatment with 15 patients receiving only their usual treatment. Participants will be assessed using questionnaires at baseline, 16 weeks (post-intervention), and 36 weeks (follow-up). DISCUSSION: Expected outcomes will include a refined study protocol and an estimate of the effect size to inform the sample size of a definitive RCT. If evidence from a fully powered RCT suggests that relating therapy is effective, the therapy will extend the range of evidence-based psychological therapies available to people who hear distressing voices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN registration number 44114663. Registered on 13 June 2013. PMID- 25128003 TI - Urine YKL-40 is associated with progressive acute kidney injury or death in hospitalized patients. AB - BACKGROUND: A translational study in renal transplantation suggested YKL-40, a chitinase 3-like-1 gene product, plays an important role in acute kidney injury (AKI) and repair, but data are lacking about this protein in urine from native human kidneys. METHODS: This is an ancillary study to a single-center, prospective observational cohort of patients with clinically-defined AKI according to AKI Network serum creatinine criteria. We determined the association of YKL -40 >= 5 ng/ml, alone or combined with neutrophil gelatinase-associated lipocalin (NGAL), in urine collected on the first day of AKI with a clinically important composite outcome (progression to higher AKI stage and/or in-hospital death). RESULTS: YKL-40 was detectable in all 249 patients, but urinary concentrations were considerably lower than in previously measured deceased-donor kidney transplant recipients. Seventy-two patients (29%) progressed or died in hospital, and YKL-40 >= 5 ng/ml had an adjusted odds ratio (95% confidence interval) for the outcome of 3.4 (1.5-7.7). The addition of YKL-40 to a clinical model for predicting the outcome resulted in a continuous net reclassification improvement of 29% (P = 0.04). In patients at high risk for the outcome based on NGAL concentrations in the upper quartile, YKL-40 further partitioned the cohort into moderate-risk and very high-risk groups. CONCLUSIONS: Urine YKL-40 is associated with AKI progression and/or death in hospitalized patients and improves clinically determined risk reclassification. Combining YKL-40 with other AKI biomarkers like NGAL may further delineate progression risk, though additional studies are needed to determine whether YKL-40 has general applicability and to define its association with longer-term outcomes in AKI. PMID- 25128005 TI - The effects of immunotherapy with intravenous immunoglobulins versus no intervention, placebo, or usual care in patients with recurrent miscarriages: a protocol for a systematic review with meta-analyses, trial sequential analyses, and individual patient data meta-analyses of randomised clinical trials. AB - BACKGROUND: Recurrent miscarriage is generally defined as three or more miscarriages before gestational week 20. Recurrent miscarriage affects 1% of all women and the condition can only be explained by parental chromosome abnormalities, uterine malformations, or endocrine or thrombophilic disturbances to a limited extent. Immunological disturbances are hypothesised to play an important role in recurrent miscarriage and, therefore, various types of immunologically-based therapies have been tested in recurrent miscarriage patients including intravenous immunoglobulins. So far, at least eight randomised placebo-controlled trials, with opposing results, investigating intravenous immunoglobulins with a total of 324 recurrent miscarriage patients have been published. METHODS/DESIGN: We will include randomised clinical trials irrespective of publication date, publication type, publication language, and publication status investigating infusions with immunoglobulins in relation to pregnancy compared to placebo, no intervention, or treatment as usual for assessments of benefits and harms. The relevant published literature will be searched using the following databases: Cochrane Central Register of Controlled Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, and Ovid Medline In-Process and Other Non-Indexed Citations databases. Two review authors will independently extract data and assess risk of bias. We will undertake meta-analyses according to the recommendations stated in the Cochrane Handbook for Systematic Reviews of Interventions. Further, we will conduct trial sequential analyses and individual patient data meta-analyses. DISCUSSION: A miscarriage results in great sorrow, loss of life quality, and personal concern. In particular, recurrent miscarriage is extremely stressful and burdensome. It is, therefore, very important to conduct research in this area. There is currently no evidence-based treatment for women with recurrent miscarriage which significantly improves their ability to give live birth. Therefore, a comprehensive up-to-date systematic review is needed. By using individual patient data, it will be possible to provide new knowledge about the benefits and harms of intravenous immunoglobulins and try to identify the subgroup in which the treatment will have the highest impact.This systematic review protocol was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42014007112. PMID- 25128007 TI - Does intravenous magnesium reduce the need for hospital admission among adult patients with acute asthma exacerbations? PMID- 25128006 TI - [Sudden cardiac death in individuals with normal hearts: an update]. AB - Sudden death (SD) is a tragic event and a world-wide health problem. Every year, near 4-5 million people experience SD. SD is defined as the death occurred in 1h after the onset of symptoms in a person without previous signs of fatality. It can be named "recovered SD" when the case received medical attention, cardiac reanimation effective defibrillation or both, surviving the fatal arrhythmia. Cardiac channelopathies are a group of diseases characterized by abnormal ion channel function due to genetic mutations in ion channel genes, providing increased susceptibility to develop cardiac arrhythmias and SD. Usually the death occurs before 40 years of age and in the autopsy the heart is normal. In this review we discuss the main cardiac channelopathies involved in sudden cardiac death along with current management of cases and family members that have experienced such tragic event. PMID- 25128008 TI - Emergency care and the national quality strategy: highlights from the Centers for Medicare & Medicaid Services. AB - The Centers for Medicare & Medicaid Services (CMS) of the US Department of Health and Human Services seeks to optimize health outcomes by leading clinical quality improvement and health system transformation through a variety of activities, including quality measure alignment, prioritization, and implementation. CMS manages more than 20 federal quality measurement and public reporting programs that cover the gamut of health care providers and facilities, including both hospital-based emergency departments (EDs) and individual emergency physicians. With more than 130 million annual visits, and as the primary portal of hospital admission, US hospital-based EDs deliver a substantial portion of acute care to Medicare beneficiaries. Given the position of emergency care across clinical conditions and between multiple settings of care, the ED plays a critical role in fulfilling all 6 priorities of the National Quality Strategy. We outline current CMS initiatives and future opportunities for emergency physicians and EDs to effect each of these priorities and help CMS achieve the triple aim of better health, better health care, and lower costs. PMID- 25128009 TI - Advancing regulatory science to bring novel medical devices for use in emergency care to market: the role of the Food and Drug Administration. AB - The Food and Drug Administration (FDA) performs regulatory science to provide science-based medical product regulatory decisions. This article describes the types of scientific research the FDA's Center for Devices and Radiological Health performs and highlights specific projects related to medical devices for emergency medicine. In addition, this article discusses how results from regulatory science are used by the FDA to support the regulatory process as well as how the results are communicated to the public. Regulatory science supports the FDA's mission to assure safe, effective, and high-quality medical products are available to patients. PMID- 25128010 TI - Acute HIV infection and implications of fourth-generation HIV screening in emergency departments. PMID- 25128011 TI - A cross-sectional retrospective analysis of the regionalization of complex surgery. AB - BACKGROUND: The Veterans Health Administration (VHA) system has assigned a surgical complexity level to each of its medical centers by specifying requirements to perform standard, intermediate or complex surgical procedures. No study to similarly describe the patterns of relative surgical complexity among a population of United States (U.S) civilian hospitals has been completed. METHODS: DESIGN: single year, retrospective, cross-sectional. SETTING/PARTICIPANTS: the study used Florida Inpatient Discharge Data from short-term acute hospitals for calendar year 2009. Two hundred hospitals with 2,542,920 discharges were organized into four quartiles (Q 1, 2, 3, 4) based on the number of complex procedures per hospital. The VHA surgical complexity matrix was applied to assign relative complexity to each procedure. The Clinical Classification Software (CCS) system assigned complex procedures to clinically meaningful groups. For outcome comparisons, propensity score matching methods adjusted for the surgical procedure, age, gender, race, comorbidities, mechanical ventilator use and type of admission. MAIN OUTCOME MEASURES: in-hospital mortality and length-of-stay (LOS). RESULTS: Only 5.2% of all inpatient discharges involve a complex procedure. The highest volume complex procedure hospitals (Q4) have 49.8% of all discharges but 70.1% of all complex procedures. In the 133,436 discharges with a primary complex procedure, 374 separate specific procedures are identified, only about one third of which are performed in the lowest volume complex procedure (Q1) hospitals. Complex operations of the digestive, respiratory, integumentary and musculoskeletal systems are the least concentrated and proportionately more likely to occur in the lower volume hospitals. Operations of the cardiovascular system and certain technology dependent miscellaneous diagnostic and therapeutic procedures are the most concentrated in high volume hospitals. Organ transplants are only done in Q4 hospitals. There were no significant differences in in hospital mortality rates and the longest lengths of stay were found in higher volume hospitals. CONCLUSIONS: Complex surgery in Florida is effectively regionalized so that small volume hospitals operating within the range of complex procedures appropriate to their capabilities provide no increased risk of post surgical mortality. PMID- 25128013 TI - Denosumab for the management of hypercalcemia of malignancy in patients with multiple myeloma and renal dysfunction. PMID- 25128012 TI - Pumping iron. AB - The primary role of the ZIP13 metal transporter in flies is to move iron ions out of cells, rather than moving zinc ions into cells, as is the case in human cells. PMID- 25128014 TI - The impact of preoperative patient characteristics on the cost-effectiveness of total hip replacement: a cohort study. AB - BACKGROUND: To facilitate the discussion on the increasing number of total hip replacements (THR) and their effectiveness, we apply a joint evaluation of hospital case costs and health outcomes at the patient level to enable comparative effectiveness research (CER) based on the preoperative health state. METHODS: In 2012, 292 patients from a German orthopedic hospital participated in health state evaluation before and 6 months after THR, where health-related quality of life (HRQoL) and disease specific pain and dysfunction were analyzed using EQ-5D and WOMAC scores. Costs were measured with a patient-based DRG costing scheme in a prospective observation of a cohort. Costs per quality adjusted life year (QALY) were calculated based on the preoperative WOMAC score, as preoperative health states were found to be the best predictors of QALY gains in multivariate linear regressions. RESULTS: Mean inpatient costs of THR were 6,310 Euros for primary replacement and 7,730 Euros for inpatient lifetime costs including revisions. QALYs gained using the U.K. population preference-weighted index were 5.95. Lifetime costs per QALY were 1,300 Euros. CONCLUSIONS: The WOMAC score and the EQ-5D score before operation were the most important predictors of QALY gains. The poorer the WOMAC score or the EQ-5D score before operation, the higher the patient benefit. Costs per QALY were far below common thresholds in all preoperative utility score groups and with all underlying calculation methodologies. PMID- 25128015 TI - Transcriptome sequencing and analysis of the zoonotic parasite Spirometra erinacei spargana (plerocercoids). AB - BACKGROUND: Although spargana, which are the plerocercoids of Spirometra erinacei, are of biological and clinical importance, expressed sequence tags (ESTs) from this parasite have not been explored. To understand molecular and biological features of this parasite, sparganum ESTs were examined by large-scale EST sequencing and multiple bioinformatics tools. METHODS: Total RNA was isolated from spargana and then ESTs were generated, assembled and sequenced. Many biological aspects of spargana were investigated using multi-step bioinformatics tools. RESULTS: A total of 5,634 ESTs were collected from spargana. After clustering and assembly, the functions of 1,794 Sparganum Assembled ESTs (SpAEs) including 934 contigs and 860 singletons were analyzed. A total of 1,351 (75%) SpAEs were annotated using a hybrid of BLASTX and InterProScan. Of these genes, 1,041 (58%) SpAEs had high similarity to tapeworms. In the context of the biology of sparganum, our analyses reveal: (i) a highly expressed fibronectin 1, a ubiquitous and abundant glycoprotein; (ii) up-regulation of enzymes related with glycolysis pathway; (iii) most frequent domains of protein kinase and RNA recognition motif domain; (iv) a set of helminth-parasitic and spargana-specific genes that may offer a number of antigen candidates. CONCLUSIONS: Our transcriptomic analysis of S. erinacei spargana demonstrates biological aspects of a parasite that invades and travels through subcutaneous tissue in intermediate hosts. Future studies should include comparative analyses using combinations of transcriptome and proteome data collected from the entire life cycle of S. erinacei. PMID- 25128016 TI - Recombinant activated factor VIIa to treat refractory lower gastrointestinal hemorrhage in a patient with recently implanted mechanical valve: a case report. AB - BACKGROUND: Bleeding is a common complication after cardiac surgery. However, lower gastrointestinal bleeding is not usually associated with this type of surgery. CASE PRESENTATION: A 50-year-old man with a history of aortic regurgitation underwent elective mechanical valve replacement under cardiopulmonary bypass. He experienced a complicated intraoperative course involving unexplained cardiac arrest following induction of anesthesia. He also developed two episodes of massive lower gastrointestinal bleeding secondary to mucosal ischemia while convalescing in the cardiothoracic surgery intensive care unit. After unsuccessful attempts to control the bleeding, exhaustion of blood products, and consideration of the high risk of mortality associated with surgery and the possibility of early- and long-term surgical complications, the decision was made to administer two successive doses of recombinant activated factor VII at 60 mcg/kg. Hemostasis was achieved without adverse systemic or valvular effects. CONCLUSIONS: A favorable outcome was achieved after administration of recombinant activated factor VII, which controlled the patient's severe lower gastrointestinal bleeding. This outcome suggests the need to raise awareness about the use of this drug in dire circumstances when other conventional measures fail or are unsuitable. PMID- 25128018 TI - Paroxysmal nocturnal hemoglobinuria in an 86 year old woman. PMID- 25128017 TI - HiChIP: a high-throughput pipeline for integrative analysis of ChIP-Seq data. AB - BACKGROUND: Chromatin immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-Seq) has been widely used to identify genomic loci of transcription factor (TF) binding and histone modifications. ChIP-Seq data analysis involves multiple steps from read mapping and peak calling to data integration and interpretation. It remains challenging and time-consuming to process large amounts of ChIP-Seq data derived from different antibodies or experimental designs using the same approach. To address this challenge, there is a need for a comprehensive analysis pipeline with flexible settings to accelerate the utilization of this powerful technology in epigenetics research. RESULTS: We have developed a highly integrative pipeline, termed HiChIP for systematic analysis of ChIP-Seq data. HiChIP incorporates several open source software packages selected based on internal assessments and published comparisons. It also includes a set of tools developed in-house. This workflow enables the analysis of both paired-end and single-end ChIP-Seq reads, with or without replicates for the characterization and annotation of both punctate and diffuse binding sites. The main functionality of HiChIP includes: (a) read quality checking; (b) read mapping and filtering; (c) peak calling and peak consistency analysis; and (d) result visualization. In addition, this pipeline contains modules for generating binding profiles over selected genomic features, de novo motif finding from transcription factor (TF) binding sites and functional annotation of peak associated genes. CONCLUSIONS: HiChIP is a comprehensive analysis pipeline that can be configured to analyze ChIP-Seq data derived from varying antibodies and experiment designs. Using public ChIP-Seq data we demonstrate that HiChIP is a fast and reliable pipeline for processing large amounts of ChIP-Seq data. PMID- 25128020 TI - Monolithic superelastic rods with variable flexural stiffness for spinal fusion: modeling of the processing-properties relationship. AB - The concept of a monolithic Ti-Ni spinal rod with variable flexural stiffness is proposed to reduce the risks associated with spinal fusion. The variable stiffness is conferred to the rod using the Joule-heating local annealing technique. The annealing temperature and the mechanical properties' distributions resulted from this thermal treatment are numerically modeled and experimentally measured. To illustrate the possible applications of such a modeling approach, two case studies are presented: (a) optimization of the Joule-heating strategy to reduce annealing time, and (b) modulation of the rod's overall flexural stiffness using partial annealing. A numerical model of a human spine coupled with the model of the variable flexural stiffness spinal rod developed in this work can ultimately be used to maximize the stabilization capability of spinal instrumentation, while simultaneously decreasing the risks associated with spinal fusion. PMID- 25128019 TI - The cytokines within the carotid plaque in symptomatic patients with internal carotid artery stenosis. AB - The aim of the study was the evaluation of the inflammatory cytokines within atheromatic carotid plaque. MATERIALS AND METHODS: The experiment was carried out on 100 symptomatic patients with internal carotid artery stenosis that underwent carotid endarterectomy. Every patient had the wall of the carotid artery resected during organ harvesting surgery in order to evaluate some cytokines (TGF-beta, VEGF, FGF, TNF-alpha) and to perform the immunohistochemistry (IHC). An immunoreactive score (IRS) was calculated based on the staining intensity and the number of cells stained. Over a 3-year period, 7 patients died, and 2 patients were lost to follow-up. The study group consisted of 91 patients. The control group comprised 20 young organ donors with confirmed death brain, who had their normal carotid artery sampled. RESULTS: In all healthy donors (control group) with normal carotid arteries the three cytokines (TGF-beta, VEGF, TNF-alpha) were not discovered. The presence of FGF was confirmed in 25% of healthy donors, probably due to an intima fibroblasts activity, responsible for the synthesis of elastin and collagen to the extracellular matrix (ECM). Only three cytokines (TGF beta, FGF, TNF-alpha) were found within atheromatous plaques (study group). CONCLUSIONS: Our research confirmed that these factors may accelerate the development of atheromatic plaque and its destabilisation. PMID- 25128021 TI - "You need to take care of it like you take care of your soul": perceptions and behaviours related to mosquito net damage, care, and repair in Senegal. AB - BACKGROUND: Net care and repair behaviours are essential for prolonging the durability of long-lasting insecticidal nets. Increased net durability has implications for protection against malaria as well as cost savings from less frequent net distributions. This study investigated behaviours and motivations for net care and repair behaviours in Senegal with the aim of informing social and behaviour change communication (SBCC) programmes, using the Health Belief Model as a framework. METHODS: Data were collected from 114 participants in eight regions of Senegal. Participants were eligible for the study if they were at least 18 years old and if their household owned at least one net. These respondents included 56 in-depth interview respondents and eight focus groups with 58 participants. In addition, the qualitative data were supplemented with observational questionnaire data from a total of 556 sleeping spaces. Of these spaces, 394 had an associated net. RESULTS: Reported net care and repair behaviours and motivations varied substantially within this sample. Children and improper handling were seen as major sources of net damage and respondents often tried to prevent damage by storing nets when not in use. Washing was seen as an additional method of care, but practices for washing varied and may have been damaging to nets in some cases. Participants mentioned a sense of pride of having a net in good condition and the uncertainty around when they could expect another net distribution as motivations for net care. Net repair appeared to be a less common behaviour and was limited by the perspective that net degradation was inevitable and that repairs themselves could weaken nets. CONCLUSION: These findings can be understood using the Health Belief Model framework of perceived severity, perceived susceptibility, perceived barriers, perceived benefits, self efficacy, and cues to action. This model can guide SBCC messages surrounding net care and repair to promote practices associated with net longevity. Such messages should promote the benefits of intact nets and provide tools for overcoming barriers to care and repair. PMID- 25128022 TI - Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi center randomized clinical trial. AB - INTRODUCTION: Because of ongoing controversy, renal and vital outcomes are compared between systemically administered unfractionated heparin and regional anticoagulation with citrate-buffered replacement solution in predilution mode, during continuous venovenous hemofiltration (CVVH) in critically ill patients with acute kidney injury (AKI). METHODS: In this multi-center randomized controlled trial, patients admitted to the intensive care unit requiring CVVH and meeting inclusion criteria, were randomly assigned to citrate or heparin. Primary endpoints were mortality and renal outcome in intention-to-treat analysis. Secondary endpoints were safety and efficacy. Safety was defined as absence of any adverse event necessitating discontinuation of the assigned anticoagulant. For efficacy, among other parameters, survival times of the first hemofilter were studied. RESULTS: Of the 139 patients enrolled, 66 were randomized to citrate and 73 to heparin. Mortality rates at 28 and 90 days did not differ between groups: 22/66 (33%) of citrate-treated patients died versus 25/72 (35%) of heparin treated patients at 28 days, and 27/65 (42%) of citrate-treated patients died versus 29/69 (42%) of heparin-treated patients at 90 days (P = 1.00 for both). Renal outcome, i.e. independency of renal replacement therapy 28 days after initiation of CVVH in surviving patients, did not differ between groups: 29/43 (67%) in the citrate-treated patients versus 33/47 (70%) in heparin-treated patients (P = 0.82). Heparin was discontinued in 24/73 (33%) of patients whereas citrate was discontinued in 5/66 (8%) of patients (P < 0.001). Filter survival times were superior for citrate (median 46 versus 32 hours, P = 0.02), as were the number of filters used (P = 0.002) and the off time within 72 hours (P = 0.002). The costs during the first 72 hours of prescribed CVVH were lower in citrate-based CVVH. CONCLUSIONS: Renal outcome and patient mortality were similar for citrate and heparin anticoagulation during CVVH in the critically ill patient with AKI. However, citrate was superior in terms of safety, efficacy and costs. TRIAL REGISTRATION: Clinicaltrials.gov NCT00209378. Registered 13th September 2005. PMID- 25128023 TI - A longitudinal study investigating quality of life and nutritional outcomes in advanced cancer patients receiving home parenteral nutrition. AB - BACKGROUND: In cancer patients where gastrointestinal function is marginal and malnutrition significant enough to result in the requirement for intensive nutrition support, parenteral nutrition (PN) is indicated. This longitudinal study examined the quality of life (QoL) and nutritional outcomes in advanced cancer patients receiving home PN (HPN). METHODS: Fifty-two adult cancer patients (21 males, 31 females, average age 53 years) treated at a specialized cancer facility between April 2009 and November 2011 met criteria. QoL and nutritional status were measured at baseline and every month while on HPN using EORTC-QLQ C30, Karnofsky Performance Status (KPS), and Subjective Global Assessment (SGA). Repeated measures ANOVA and Generalized Estimating Equations (GEE) were used to evaluate longitudinal changes in QoL and SGA. RESULTS: Cancer diagnoses included pancreatic (n = 14), colorectal (n = 11), ovarian (n = 6), appendix (n = 5), stomach (n = 4) and others (n = 12). Average weight loss 6-months prior to HPN was 13.2 kg (16.9%). Average weight at initiation of HPN was 62.2 kg. In patients with available follow-up data after 1 month (n = 39), there was a significant improvement in SGA, weight (61.5 to 63.1 kg; p = 0.03) and KPS (61.6 to 67.3; p = 0.01) from baseline. Similarly, after 2 months (n = 22), there was an improvement in global QoL (37.1 to 49.2; p = 0.02), SGA, weight (57.6 to 60 kg; p = 0.04) and KPS (63.2 to 73.2; p = 0.01) from baseline. Finally, after 3 months (n = 15), there was an improvement in global QoL (30.6 to 54.4; p = 0.02), SGA, weight (61.1 to 65.9 kg; p = 0.04) and KPS (64.0 to 78.7; p = 0.002) from baseline. Upon GEE analysis, every 1 month of HPN was associated with an increase of 6.3 points in global QoL (p<0.001), 1.3 kg in weight (p = 0.009) and 5.8 points in KPS (p<0.001). CONCLUSIONS: HPN is associated with an improvement in QoL, KPS and nutritional status in advanced cancer patients, irrespective of their tumor type, who have compromised enteral intake and malnutrition. The greatest benefit was seen in patients with 3 months of HPN, although patients receiving HPN for 1 or 2 months also demonstrated significant improvements. PMID- 25128024 TI - The association between air pollutants and morbidity for diabetes and liver diseases modified by sexes, ages, and seasons in Tianjin, China. AB - With the generalized linear model and natural splines (ns), we examined the association between outdoor air pollutants and daily morbidity for diabetes and liver disease stratified by sexes and ages based on 4 years of daily data (2008 2011) in Tianjin, China. Season effects of air pollutants including particulate matter (PM), sulfur dioxide (SO2), and nitrogen dioxide (NO2) were also investigated. An increase of 10 MUg/m(3) in a 2-day average concentrations of particulate matter with diameters of 10 MUm or less (PM10), SO2, and NO2 corresponds to increases in diabetes morbidity of 0.39 % (95 % confidence interval (CI), -0.42-1.12), 0.15 % (95 % CI, -0.25-0.54), and 1.22 % (95 % CI, 0.51-2.96), respectively. As for liver morbidity, the increases were -0.84 % (95 % CI, -2.33-0.62), 0.90 % (95 % CI, 0.50-1.74), and 1.10 % (95 % CI, -2.58-4.78), respectively. The effects were stronger in the cool season than those in the warm season; females and the elderly were generally more vulnerable to outdoor air pollution. This study possesses scientific implications and instructional significance for local environmental standards and medical policymaking. PMID- 25128025 TI - Enhanced amyloidogenic processing of amyloid precursor protein and cell death under prolonged endoplasmic reticulum stress in brain endothelial cells. AB - Cerebral amyloid angiopathy resulting from the deposition of misfolded amyloid beta (Abeta) peptide in the walls of brain's blood vessels is exhibited by the majority of Alzheimer's disease (AD) patients, suggesting that alterations in protein quality control contribute to AD-associated vascular dysfunction. The present work addressed the role of ER stress in the amyloidogenic amyloid precursor protein (APP) processing and subsequent Abeta generation in brain endothelial cells (ECs). For that purpose, the RBE4 cell line was exposed to the classical ER stressors thapsigargin or brefeldin A to mimic the altered ER homeostasis observed in AD. In treated cells, an increase in the levels of markers of ER stress (XBP1 and GRP78) and of the ER stress-induced apoptotic pathway (caspase-12, JNK, and CHOP) was observed concomitantly with the accumulation of reactive oxygen species. Under these conditions, a significant ER to-mitochondria Ca(2+) transfer was also found, which culminated in mitochondrial Ca(2+) overload and activation of mitochondria-dependent apoptosis. Moreover, it was showed that prolonged ER stress induces intracellular APP accumulation, which colocalizes with the ER chaperone GRP78, and activation of beta-secretase, leading to increased intracellular Abeta levels, together with a decrease in secreted Abeta. Finally, it was demonstrated that ER stress-induced changes in Abeta levels and apoptotic cell death can be ameliorated by a blocker of the mitochondrial Bax channel. These observations suggest that chronic ER stress triggers APP accumulation in early comportments along the secretory pathway in brain ECs and increases its amyloidogenic processing and Abeta generation leading to apoptotic cell death. PMID- 25128026 TI - Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates MPTP-Induced Parkinsonism. AB - Soluble epoxide hydrolase (sEH) inhibition has been demonstrated to have beneficial effects on various diseases, such as hypertension, diabetes, and brain ischemia. However, whether sEH inhibition has therapeutic potential in Parkinson's disease is still unknown. In this paper, we found that sEH expression is increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-treated mice, and sEH deficiency and inhibition significantly attenuated tyrosine hydroxylase (TH)-positive cell loss and improved rotarod performance. The substrate of sEH, 14,15-epoxyeicosatrienoic acid (14,15-EET), protected TH positive cells and alleviated the rotarod performance deficits of wild-type mice but not sEH-knockout mice. Moreover, the 14,15-EET antagonist 14,15-epoxyeicosa 5(Z)-enoic acid (14,15-EEZE) abolished the neuronal protective effects of sEH deficiency. In primary cultured cortical neurons, MPP(+) induced significant Akt inactivation in neurons from sEH wild-type mice, and this effect was not observed in neurons from knockout mice. Our data indicate that sEH deficiency and inhibition increased 14,15-EET in MPTP-treated mice, which activated the Akt mediated protection of TH-positive neurons and behavioral functioning. We also found that sEH deficiency attenuated TH-positive cell loss in a paraquat-induced mouse model of Parkinson's. Our data suggest that sEH inhibition might be a powerful tool to protect dopaminergic neurons in Parkinson's disease. PMID- 25128027 TI - Attenuated Blood-Brain Barrier Dysfunction by XQ-1H Following Ischemic Stroke in Hyperlipidemic Rats. AB - Following ischemic stroke, blood-brain barrier (BBB) is disrupted and is further aggravated with the corresponding incidence of hyperlipidemia. BBB breakdown promotes inflammation infiltration into the brain, which exacerbates cerebral ischemic injury as a result. Here, we report that 10-O-(N,N-dimethylaminoethyl) ginkgolide B methanesulfonate (XQ-1H), a novel analog of ginkgolide B, alleviates BBB breakdown in hyperlipidemic rats and protects endothelial cells against inflammatory response. Middle cerebral artery occlusion (MCAO) modeled ischemic stroke in rats. Before surgery, these rats were fed a cholesterol-rich diet to induce an experimental hyperlipidemic condition. Additionally, lipopolysaccharide (LPS) incubation with rat brain microvessel endothelial cells (rBMECs) was applied to mimic hyperlipidemia-induced inflammatory injury of BBB. The results indicated more severe infarct size, increased BBB permeability, excessive secretion of pro-inflammatory cytokines, and exaggerated inflammation infiltration of the brain in hyperlipidemic rats following MCAO when compared to rats fed with normal diet. XQ-1H protected BBB integrity, lessoned brain edema and inflammation penetration, downregulated MMP-9 and VCMA-1 expressions, and extenuated ischemic infarction. XQ-1H alleviated LPS-induced inflammatory response in rBMECs, characterized by promoting cell viability, inhibiting TNF alpha, IL-1beta, and IL-6 releasing, and downregulating NF-kappaB inflammatory signal and downstream proteins, such as VCAM-1 and iNOS. In conclusion, the present study shows that XQ-1H stabilizes BBB function following ischemic stroke in hyperlipidemic rats, and the possible mechanisms may be related to inflammation inhibition. PMID- 25128028 TI - AP-1/sigma1B-Dependent SV Protein Recycling Is Regulated in Early Endosomes and Is Coupled to AP-2 Endocytosis. AB - Adaptor protein (AP)-1/sigma1B(-/-) mice have reduced synaptic-vesicle (SV) recycling and increased endosomes. Mutant mice have impaired spatial memory, and sigma1B-deficient humans have a severe mental retardation. In order to define these sigma1B(-/-) 'bulk' endosomes and to determine their functions in SV recycling, we developed a protocol to separate them from the majority of the neuronal endosomes. The sigma1B(-/-) 'bulk' endosomes proved to be classic early endosomes with an increase in the phospholipid phosphatidylinositol 3-phosphate (PI-3-P), which recruits proteins mediating protein sorting out of early endosomes into different routes. sigma1B deficiency induced alterations in the endosomal proteome reveals two major functions: SV protein storage and sorting into endolysosomes. Alternative endosomal recycling pathways are not up regulated, but certain SV proteins are misrouted. Tetraspanins are enriched in sigma1B(-/-) synaptosomes, but not in their endosomes or in their clathrin-coated vesicles (CCVs), indicating AP-1/sigma1B-dependent sorting. Synapses contain also more AP-2 CCV, although it is expected that they contain less due to reduced SV recycling. Coat composition of these AP-2 CCVs is altered, and thus, they represent a subpopulation of AP-2 CCVs. Association of calmodulin-dependent protein kinase (CaMK)-IIalpha, -delta and casein kinase (CK)-IIalpha with the endosome/SV pool is altered, as well as 14-3-3eta, indicating changes in specific signalling pathways regulating synaptic plasticity. The accumulation of early endosomes and endocytotic AP-2 CCV indicates the regulation of SV recycling via early endosomes by the interdependent regulation of AP-2-mediated endocytosis and AP-1/sigma1B-mediated SV reformation. PMID- 25128029 TI - Memory Impairment in Estrogen Receptor alpha Knockout Mice Through Accumulation of Amyloid-beta Peptides. AB - Estrogen has been known to reduce the development of Alzheimer's disease (AD). However, exact mechanisms are not clear. We investigated whether estrogen can increase amyloid-beta (Abeta) degradation and affects Abeta-induced memory impairment in an estrogen deficiency model. Estrogen receptor alpha (ERalpha) knockout mice and wild-type mice were intracerebroventricular (ICV) infused with Abeta (300 pmol) for 2 weeks. Cognitive function was then assessed by the Morris water maze test and passive avoidance test. In addition, Western blot analysis, immunostaining, immunofluorescence staining, ELISA, and enzyme activity assays were used to examine the degree of Abeta deposition in the brains of ERalpha knockout mice. In our present study, Abeta was accumulated more in the ERalpha knockout mice brain and greatly worsened memory impairment and glial activation as well as neurogenic inflammation. These results suggest that estrogen may protect memory impairment by stimulating the degradation of Abeta and down regulate neurogenic inflammation as well as amyloidogenesis. PMID- 25128032 TI - Re: risk factors for umbilical trocar site incisional hernia in laparoscopic cholecystectomy: a prospective 3-year follow-up study. PMID- 25128031 TI - Plants and microbes assisted selenium nanoparticles: characterization and application. AB - Selenium is an essential trace element and is an essential component of many enzymes without which they become inactive. The Se nanoparticles of varying shape and size may be synthesized from Se salts especially selenite and selenates in presence of reducing agents such as proteins, phenols, alcohols and amines. These biomolecules can be used to reduce Se salts in vitro but the byproducts released in the environment may be hazardous to flora and fauna. In this review, therefore, we analysed in depth, the biogenic synthesis of Se nanoparticles, their characterization and transformation into t- Se, m-Se, Se-nanoballs, Se nanowires and Se-hollow spheres in an innocuous way preventing the environment from pollution. Their shape, size, FTIR, UV-vis, Raman spectra, SEM, TEM images and XRD pattern have been analysed. The weak forces involved in aggregation and transformation of one nano structure into the other have been carefully resolved. PMID- 25128033 TI - Difference of the associations between self-rated health and demographic characteristics, lifestyle, and psychosocial work environment between two types of Chinese worksite. AB - BACKGROUND: Although studies of self-rated health (SRH) are conducted widely in developed countries, comprehensive assessments of the determinants of SRH in Chinese are scarce, particularly for working Chinese individuals. Determinants of SRH might differ among worksites based on differences in the nature and stress associated with different jobs, work intensity, and the lifestyles of employees. METHODS: Two thousand and forty questionnaires that addressed SRH, demographic characteristics, lifestyle, and the psychosocial work environment were administered to employees at two worksites. A total of 1644 subjects provided complete data for analysis (80.6% response rate). RESULTS: Participants from government departments had significantly better SRH than did those from high-tech enterprises (61.1% vs. 67.5%, respectively). Lifestyles were significantly less healthy at government departments compared with high-tech enterprises, whereas the psychosocial work environment was better. The results of unadjusted and adjusted models revealed differences between the potential health-influencing factors of participants based on their type of worksite. In logistic regression models, gender was strongly associated with SRH in all participants, whereas length of service was correlated with SRH only in participants from high-tech enterprises. In high-tech enterprises, good SRH was less common in physically inactive subjects vs. physically active participants (OR = 0.561). In government departments, passive smoking was negatively associated with SRH significantly. Social capital (OR = 1.073) and job control (OR = 1.550) were positively correlated with SRH in high-tech enterprises. Job control was the only psychosocial factor significantly associated with SRH in government departments. CONCLUSIONS: Participants from different types of worksite reported different SRH, healthy lifestyles, and psychosocial work environments. Moreover, the association between SRH and demographic characteristics, lifestyle, and the psychosocial work environment significantly differed by type of worksite. PMID- 25128030 TI - Protective Effect of a cAMP Analogue on Behavioral Deficits and Neuropathological Changes in Cuprizone Model of Demyelination. AB - Multiple sclerosis (MS) is an inflammatory demyelinating disease that leads to neuronal cell loss. Cyclic AMP and its analogs are well known to decrease inflammation and apoptosis. In the present study, we examined the effects of bucladesine, a cell-permeable analogue of cyclic adenosine monophosphate (cAMP), on myelin proteins (PLP, PMP-22), inflammation, and apoptotic, as well as anti apoptotic factors in cuprizone model of demyelination. C57BL/6J mice were fed with chow containing 0.2% copper chelator cuprizone or vehicle by daily oral gavage for 5 weeks to induce reversible demyelination predominantly of the corpus callosum. Bucladesine was administered intraperitoneally at different doses (0.24, 0.48, or 0.7 MUg/kg body weight) during the last 7 days of 5-week cuprizone treatment. Bucladesine exhibited a protective effect on myelination. Furthermore, bucladesine significantly decreased the production of interleukin-6 pro-inflammatory mediator as well as nuclear factor-kappaB activation and reduced the mean number of apoptotic cells compared to cuprizone-treated mice. Bucladesine also decreased production of caspase-3 as well as Bax and increased Bcl-2 levels. Our data revealed that enhancement of intracellular cAMP prevents demyelination and plays anti-inflammatory and anti-apoptotic properties in mice cuprizone model of demyelination. This suggests the modulation of intracellular cAMP as a potential target for treatment of MS. PMID- 25128034 TI - Spatial epidemiology of dry eye disease: findings from South Korea. AB - BACKGROUND: DED rate maps from diverse regions may allow us to understand world wide spreading pattern of the disease. Only few studies compared the prevalence of DED between geographical regions in non-spatial context. Therefore, we examined the spatial epidemiological pattern of DED prevalence in South Korea using a nationally representative sample. METHODS: We analyzed 16,431 Korean adults aged 30 years or older of the 5th Korea National Health and Nutrition Examination Survey. DED was defined as previously diagnosed by an ophthalmologist as well as symptoms experienced. Multiple logistic regression analysis was used to assess the spatial pattern in the prevalence of DED, and effects of environmental factors. RESULTS: Among seven metropolitan cities and nine provinces, three metropolitan cities located in the southeast of Korea revealed the highest prevalence of DED. After adjusting for sex, age and survey year, people living in urban areas had higher risk of having DED. Adjusted odds ratio for having previously diagnosed DED was 1.677 (95% CI 1.299-2.166) for metropolitan cities and 1.580 (95% CI 1.215-2.055) for other cities compared to rural areas. Corresponding odds ratio for presenting DED symptoms was 1.388 (95% CI 1.090-1.766) for metropolitan cities and 1.271 (95% CI 0.999-1.617) for other cities. Lower humidity and longer sunshine duration were significantly associated with DED. Among air pollutants, SO2 was associated with DED, while NO2, O3, CO, and PM10 were not. CONCLUSION: Our findings suggest that prevalence of DED can be affected by the degree of urbanization and environmental factors such as humidity and sunshine duration. PMID- 25128036 TI - Use of FRAX as a determinant for risk-based osteoporosis screening may decrease unnecessary testing while improving the odds of identifying treatment candidates. AB - PURPOSE: We have assessed the hypothetical impact of guideline-concordant osteoporosis screening on baseline behaviors utilizing two different guidelines and determined the relative ability of each to identify osteoporosis treatment candidates. METHODS: We conducted secondary analyses from the Fracture Risk Perception Study, which enrolled patients aged 50 to 75 years to complete questionnaires about their bone health. We determined our baseline screening rates and detection of treatment candidates and then assessed the hypothetical impact of adherence to U.S. Preventive Services Task Force (USPSTF) and National Osteoporosis Foundation (NOF) criteria, particularly for women aged 50 to 64. RESULTS: Of 144 women aged 50 to 64 years screened, 14 (9.7%) were treatment candidates. Screening based on identification of one or more risks (NOF) would lead to testing of 102 of the 144 patients (71%) to identify 12 of 14 treatment candidates (86%). Applying USPSTF criteria (9.3% FRAX threshold) would test 45 of the same 144 women (31%) to identify 11 of 14 treatment candidates (79%). NOF risk-based criteria would result in a moderate absolute screening rate reduction (16%, p = .0011; 95% CI, 7%-25%), but only marginal improvement in identifying treatment candidates (odds ratio, 2.67; 95% CI, 0.57-12.47). Applying the more selective USPSTF criteria greatly reduced unnecessary testing (56% absolute screening rate reduction; p < .0001; 95% CI, 47%-64%) while further improving the odds of identifying treatment candidates (odds ratio, 10.35; 95% CI, 2.72-39.35). CONCLUSIONS: When contemplating screening younger patients, systematic calculation of FRAX and ordering only when the 9.3% fracture risk threshold is reached may decrease unnecessary screening for many women while still identifying appropriate osteoporosis treatment candidates. PMID- 25128037 TI - Making the most of the Affordable Care Act's contraceptive coverage mandate for privately-insured women. PMID- 25128035 TI - "When you get old like this ... you don't run those risks anymore": influence of age on sexual risk behaviors and condom use attitudes among methamphetamine-using heterosexual women with a history of partner violence. AB - BACKGROUND: Drug use and partner violence affect older women, yet few studies highlight age-specific HIV risks and prevention strategies. This study compares sexual risk behaviors, condom use attitudes, and HIV knowledge between midlife/older women (ages 45+) and younger women (ages 18-44) reporting methamphetamine use and partner violence in San Diego, California. METHODS: Our mixed methods study used themes from a qualitative substudy (n = 18) to inform logistic regression analysis of baseline data from an HIV behavioral intervention trial (n = 154). FINDINGS: Age-related qualitative themes included physiologic determinants, HIV knowledge, and "dodging the bullet," referring to a lifetime of uncertainty surrounding HIV serostatus after engaging in unsafe drug and sex practices. Midlife/older age was associated with never being married (24.2% vs. 51.2; p = .03), having less than a high school education/GED (12.1% vs. 34.7%; p = .04), lower condom use self-efficacy (2.87 vs. 3.19; p = .03), lower positive outcome expectancies (1.9 vs. 2.1; p = .04), and lower HIV knowledge (85.3% vs. 89.7%; p = .04); however, sexual risk behaviors were not associated with age group. In the multivariate analysis, midlife/older age remained independently associated with lower condom use self-efficacy (adjusted odds ratio, 0.49; 95% CI, 0.27-0.87) and lower HIV knowledge (adjusted odds ratio, 0.96; 95% CI, 0.93 0.99). CONCLUSIONS: Midlife/older methamphetamine-using women with experiences of partner violence present similar sexual risk profiles, but possess different HIV related knowledge and attitudes toward prevention methods compared with their younger counterparts. Clinicians and public health practitioners can have a positive impact on this overlooked population by assessing HIV risks during routine screenings, encouraging HIV testing, and providing age-appropriate HIV prevention education. PMID- 25128039 TI - Guidelines, training, audit, and quality standards in children's epilepsy services: closing the loop. AB - There has been considerable evolution in epilepsy healthcare for children over the last decade in the United Kingdom. There has been no single explanation for this. The development of national clinical guidelines, locally delivered but nationally designed educational programmes, nation-wide clinical audit, clinical networks and development of designated services have all had complimentary roles in enabling the implementation of national recommendations for the development of epilepsy care. These models may be applicable to other healthcare settings outside the UK. PMID- 25128040 TI - Review of the Task Force Report on PRO data collection in clinical trials using mixed modes. PMID- 25128038 TI - Racial/Ethnic, socioeconomic, and geographic disparities of cervical cancer advanced-stage diagnosis in Texas. AB - BACKGROUND: Advanced-stage diagnosis is among the primary causes of mortality among cervical cancer patients. With the wide use of Pap smear screening, cervical cancer advanced-stage diagnosis rates have decreased. However, disparities of advanced-stage diagnosis persist among different population groups. A challenging task in cervical cancer disparity reduction is to identify where underserved population groups are. METHODS: Based on cervical cancer incidence data between 1995 and 2008, this study investigated advanced-stage cervical cancer disparities in Texas from three social domains: Race/ethnicity, socioeconomic status (SES), and geographic location. Effects of individual and contextual factors, including age, tumor grade, race/ethnicity, as well as contextual SES, spatial access to health care, sociocultural factors, percentage of African Americans, and insurance expenditures, on these disparities were examined using multilevel logistic regressions. FINDINGS: Significant variations by race/ethnicity and SES were found in cervical cancer advanced-stage diagnosis. We also found a decline in racial/ethnic disparities of advanced cervical cancer diagnosis rate from 1995 to 2008. However, the progress was slower among African Americans than Hispanics. Geographic disparities could be explained by age, race/ethnicity, SES, and the percentage of African Americans in a census tract. CONCLUSIONS: Our findings have important implications for developing effective cervical cancer screening and control programs. We identified the location of underserved populations who need the most assistance with cervical cancer screening. Cervical cancer intervention programs should target Hispanics and African Americans, as well as individuals from communities with lower SES in geographic areas where higher advanced-stage diagnosis rates were identified in this study. PMID- 25128041 TI - NICE's selective application of differential discounting: ambiguous, inconsistent, and unjustified. AB - The National Institute for Health and Clinical Excellence (NICE) recently recommended differential discounting of costs and health effects in the economic appraisal of health care interventions in certain circumstances. The recommendation was published in an amendment to NICE's Guide to the Methods of Technology Appraisal. The amendment states that differential discounting should be applied where "treatment effects are both substantial in restoring health and sustained over a very long period (normally at least 30 years)." Renewed interest in differential discounting from NICE is welcome; however, the recommendation's selective application of differential discounting raises a number of concerns. The stated criteria for applying differential discounting are ambiguous. The rationale for the selective application of differential discounting has not been articulated by NICE and is questionable. The selective application of differential discounting leads to several inconsistencies, the most concerning of which is the lower valuation of health gains for those with less than 30 years remaining life expectancy, which can be interpreted as age discrimination. Furthermore, the discount rates chosen by NICE do not appear to be informed by recent advances in the theoretical understanding of differential discounting. NICE's apparent motivation for recommending differential discounting was to ensure a favorable cost-effectiveness ratio for a pediatric oncology drug. While flexibility may be appropriate to allow some interventions that exceed conventional cost-effectiveness thresholds to be adopted, the selective adjustment of appraisal methods is problematic and without justification. PMID- 25128042 TI - The role of economic evaluation in meeting IOM's recommendations on delivering high-quality cancer care. PMID- 25128043 TI - PRO data collection in clinical trials using mixed modes: report of the ISPOR PRO mixed modes good research practices task force. AB - The objective of this report was to address the use and mixing of data collection modes within and between trials in which patient-reported outcome (PRO) end points are intended to be used to support medical product labeling. The report first addresses the factors that should be considered when selecting a mode or modes of PRO data collection in a clinical trial, which is often when mixing is first considered. Next, a summary of how to "faithfully" migrate instruments is presented followed by a section on qualitative and quantitative study designs used to evaluate measurement equivalence of the new and original modes of data collection. Finally, the report discusses a number of issues that must be taken into account when mixing modes is deemed necessary or unavoidable within or between trials, including considerations of the risk of mixing at different levels within a clinical trial program and mixing between different types of platforms. In the absence of documented evidence of measurement equivalence, it is strongly recommended that a quantitative equivalence study be conducted before mixing modes in a trial to ensure that sufficient equivalence can be demonstrated to have confidence in pooling PRO data collected by the different modes. However, we also strongly discourage the mixing of paper and electronic field-based instruments and suggest that mixing of electronic modes be considered for clinical trials and only after equivalence has been established. If proceeding with mixing modes, it is important to implement data collection carefully in the trial itself in a planned manner at the country level or higher and minimize ad hoc mixing by sites or individual subjects. Finally, when mixing occurs, it must be addressed in the statistical analysis plan for the trial and the ability to pool the data must be evaluated to then evaluate treatment effects with mixed modes data. A successful mixed modes trial requires a "faithful migration," measurement equivalence established between modes, and carefully planned implementation to minimize the risk of increased measurement error impacting the power of the trial to detect a treatment effect. PMID- 25128044 TI - An economic evaluation of salt reduction policies to reduce coronary heart disease in England: a policy modeling study. AB - OBJECTIVES: Dietary salt intake has been causally linked to high blood pressure and increased risk of cardiovascular events. Cardiovascular disease causes approximately 35% of total UK deaths, at an estimated annual cost of L30 billion. The World Health Organization and the National Institute for Health and Care Excellence have recommended a reduction in the intake of salt in people's diets. This study evaluated the cost-effectiveness of four population health policies to reduce dietary salt intake on an English population to prevent coronary heart disease (CHD). METHODS: The validated IMPACT CHD model was used to quantify and compare four policies: 1) Change4Life health promotion campaign, 2) front-of-pack traffic light labeling to display salt content, 3) Food Standards Agency working with the food industry to reduce salt (voluntary), and 4) mandatory reformulation to reduce salt in processed foods. The effectiveness of these policies in reducing salt intake, and hence blood pressure, was determined by systematic literature review. The model calculated the reduction in mortality associated with each policy, quantified as life-years gained over 10 years. Policy costs were calculated using evidence from published sources. Health care costs for specific CHD patient groups were estimated. Costs were compared against a "do nothing" baseline. RESULTS: All policies resulted in a life-year gain over the baseline. Change4life and labeling each gained approximately 1960 life-years, voluntary reformulation 14,560 life-years, and mandatory reformulation 19,320 life-years. Each policy appeared cost saving, with mandatory reformulation offering the largest cost saving, more than L660 million. CONCLUSIONS: All policies to reduce dietary salt intake could gain life-years and reduce health care expenditure on coronary heart disease. PMID- 25128045 TI - Cost-effectiveness models for chronic obstructive pulmonary disease: cross-model comparison of hypothetical treatment scenarios. AB - OBJECTIVES: To compare different chronic obstructive pulmonary disease (COPD) cost-effectiveness models with respect to structure and input parameters and to cross-validate the models by running the same hypothetical treatment scenarios. METHODS: COPD modeling groups simulated four hypothetical interventions with their model and compared the results with a reference scenario of no intervention. The four interventions modeled assumed 1) 20% reduction in decline in lung function, 2) 25% reduction in exacerbation frequency, 3) 10% reduction in all-cause mortality, and 4) all these effects combined. The interventions were simulated for a 5-year and lifetime horizon with standardization, if possible, for sex, age, COPD severity, smoking status, exacerbation frequencies, mortality due to other causes, utilities, costs, and discount rates. Furthermore, uncertainty around the outcomes of intervention four was compared. RESULTS: Seven out of nine contacted COPD modeling groups agreed to participate. The 5-year incremental cost-effectiveness ratios (ICERs) for the most comprehensive intervention, intervention four, was ?17,000/quality-adjusted life-year (QALY) for two models, ?25,000 to ?28,000/QALY for three models, and ?47,000/QALY for the remaining two models. Differences in the ICERs could mainly be explained by differences in input values for disease progression, exacerbation-related mortality, and all-cause mortality, with high input values resulting in low ICERs and vice versa. Lifetime results were mainly affected by the input values for mortality. The probability of intervention four to be cost-effective at a willingness-to-pay value of ?50,000/QALY was 90% to 100% for five models and about 70% and 50% for the other two models, respectively. CONCLUSIONS: Mortality was the most important factor determining the differences in cost-effectiveness outcomes between models. PMID- 25128046 TI - Treating to target with etanercept in rheumatoid arthritis: cost-effectiveness of dose reductions when remission is achieved. AB - BACKGROUND: Current management of rheumatoid arthritis (RA) focuses on inducing remission as early as possible to avoid lasting joint damage, and maintenance of remission has become important. A 12-month clinical trial in 834 patients with moderate RA investigated whether etanercept 50 mg/wk could be reduced to half dose or discontinued in patients who achieved low disease activity after 36 weeks. OBJECTIVE: The objective of this study was to estimate the cost effectiveness of the three maintenance strategies. METHODS: A Markov model integrated the three strategies from the clinical trial and extrapolated to 10 years using data from the Swedish RA registry. Assumed treatment strategies after the trial were similar in all three arms, with patients failing to maintain remission on half-dose etanercept or methotrexate alone switching to the full dose of etanercept and patients maintaining remission on full-dose etanercept allowed switching to half dose. Resource use and utilities were taken from an observational study. Results are presented as cost/quality-adjusted life-year (QALY) (both discounted 3%) in the societal perspective. RESULTS: The cost/QALY gained with half-dose etanercept versus methotrexate ranged from ?14,000 to ?29,000: Longer simulations result in a higher cost/QALY, as the acquisition cost of etanercept increases. Half-dose etanercept technically dominates the full dose (lower costs [?-3000 to 6300] and similar effectiveness [0.007-0.011]). CONCLUSIONS: Although ultimately all three strategies explored achieve a similar outcome as all three continuously manage patients to maintain remission, it appears that a dose reduction is the most advantageous strategy in patients with moderate disease activity. PMID- 25128047 TI - A framework to evaluate the cost-effectiveness of the NADiA ProsVue slope to guide adjuvant radiotherapy among men with high-risk characteristics following prostatectomy for prostate cancer. AB - OBJECTIVES: The NADiA ProsVue is a prognostic system that measures prostate specific antigen slope to identify men at lower risk of clinical recurrence of prostate cancer after radical prostatectomy. We developed a decision-modeling framework to evaluate its cost-effectiveness to guide the use of adjuvant radiotherapy (ART). METHODS: We populated the model using patient-level data and external sources. Patients were classified as intermediate risk or high risk on the basis of Cancer of the Prostate Risk Assessment-Postsurgical (CAPRA-S) nomogram and then stratified by the ProsVue slope (<=2 pg/mL/mo; >2 pg/mL/mo) and receipt of ART. In sensitivity analyses, we varied the effect of the ProsVue slope on the use of ART and other model parameters. RESULTS: The cost effectiveness of the ProsVue-guided strategy varied widely because of small differences in quality-adjusted life-years (QALYs) at 10 years. In the intermediate-risk group, when the use of ART decreased from 20% (standard care) to 7.5% among patients with a ProsVue slope value of 2 pg/mL/mo or less, the incremental cost-effectiveness ratio was $25,160/QALY. In the high-risk group, the use of ART would have to decrease from 40% (standard care) to 11.5% among those with a ProsVue slope value of 2 pg/mL/mo or less to obtain a ratio of $50,000/QALY. The cost-effectiveness ratios were sensitive to varying benefits of salvage therapy, quality of life, and costs of ART and ProsVue testing. CONCLUSIONS: The effect of the ProsVue system on costs will be dependent on the extent to which ART decreases among men identified as having a low risk of recurrence. Its effect on QALYs will remain conditional on uncertain clinical and quality-of-life benefits associated with ART. PMID- 25128048 TI - Time is money, but how much? The monetary value of response time for Thai ambulance emergency services. AB - OBJECTIVE: To calculate the monetary value of the time factor per minute and per year for emergency services. METHODS: The monetary values for ambulance emergency services were calculated for two different time factors, response time, which is the time from when a call is received by the emergency medical service call taking center until the response team arrives at the emergency scene, and operational time, which includes the time to the hospital. The study was performed in two steps. First, marginal effects of reduced fatalities and injuries for a 1-minute change in the time factors were calculated. Second, the marginal effects and the monetary values were put together to find a value per minute. RESULTS: The values were found to be 5.5 million Thai bath/min for fatality and 326,000 baht/min for severe injury. The total monetary value for a 1 minute improvement for each dispatch, summarized over 1 year, was 1.6 billion Thai baht using response time. CONCLUSIONS: The calculated values could be used in a cost-benefit analysis of an investment reducing the response time. The results from similar studies could for example be compared to the cost of moving an ambulance station or investing in a new alarm system. PMID- 25128049 TI - A cost-effectiveness analysis of sensor-augmented insulin pump therapy and automated insulin suspension versus standard pump therapy for hypoglycemic unaware patients with type 1 diabetes. AB - OBJECTIVE: To assess the cost-effectiveness of sensor-augmented insulin pump therapy with "Low Glucose Suspend" (LGS) functionality versus standard pump therapy with self-monitoring of blood glucose in patients with type 1 diabetes who have impaired awareness of hypoglycemia. METHODS: A clinical trial-based economic evaluation was performed in which the net costs and effectiveness of the two treatment modalities were calculated and expressed as an incremental cost effectiveness ratio (ICER). The clinical outcome of interest for the evaluation was the rate of severe hypoglycemia in each arm of the LGS study. Quality-of-life utility scores were calculated using the three-level EuroQol five-dimensional questionnaire. Resource use costs were estimated using public sources. RESULTS: After 6 months, the use of sensor-augmented insulin pump therapy with LGS significantly reduced the incidence of severe hypoglycemia compared with standard pump therapy (incident rate difference 1.85 [0.17-3.53]; P = 0.037). Based on a primary randomized study, the ICER per severe hypoglycemic event avoided was $18,257 for all patients and $14,944 for those aged 12 years and older. Including all major medical resource costs (e.g., hospital admissions), the ICERs were $17,602 and $14,289, respectively. Over the 6-month period, the cost per quality adjusted life-year gained was $40,803 for patients aged 12 years and older. CONCLUSIONS: Based on the Australian experience evaluating new interventions across a broad range of therapeutic areas, sensor-augmented insulin pump therapy with LGS may be considered a cost-effective alternative to standard pump therapy with self-monitoring of blood glucose in hypoglycemia unaware patients with type 1 diabetes. PMID- 25128050 TI - Comparison of contemporaneous EQ-5D and SF-6D responses using scoring algorithms derived from similar valuation exercises. AB - OBJECTIVES: Poor agreement between preference-based health-related quality-of life instruments has been widely reported across patient and community-based samples. This study compares index scores generated from contemporaneous EQ-5D (3 level version) and SF-6D (SF-36 version) responses using scoring algorithms derived from independently-conducted Australian population-representative discrete choice experiments (DCEs), providing the first comparative analysis of health state valuations using the same method of valuation across the full value sets. METHODS: EQ-5D and SF-6D responses from seven patient data sets were transformed into health state valuations using published DCE-derived scoring algorithms. The empirical comparative evaluation consisted of graphical illustration of the location and spread of index scores, reporting of basic descriptive statistics, exploration of between-measure differences in mean index scores, and analysis of agreement. RESULTS: Compared with previously published findings regarding the comparability of "conventional" EQ-5D and SF-6D index scores, health state valuations from the DCE-derived scoring procedures showed that agreement between scores remained "fair" (intraclass correlation coefficient values across the seven data sets ranged from 0.375 to 0.615). Mean SF-6D scores were significantly lower than the respective mean EQ-5D score across all patient groups (mean difference for the whole sample = 0.253). CONCLUSIONS: The magnitude of disagreement previously reported between EQ-5D and SF-6D index scores is not ameliorated through the application of DCE-derived value sets; sizeable discrepancies remain. These findings suggest that differences between EQ-5D and SF-6D index scores persist because of their respective descriptive systems. Further research is required to explore the implications of variations in the descriptive systems of preference-based instruments. PMID- 25128051 TI - The effect of presenting information about invasive follow-up testing on individuals' noninvasive colorectal cancer screening participation decision: results from a discrete choice experiment. AB - OBJECTIVES: Many national colorectal cancer screening campaigns have a similar structure. First, individuals are invited to take a noninvasive screening test, and, second, in the case of a positive screening test result, they are advised to undergo a more invasive follow-up test. The objective of this study was to investigate how much individuals' participation decision in noninvasive screening is affected by the presence or absence of detailed information about invasive follow-up testing and how this effect varies over screening tests. METHODS: We used a labeled discrete choice experiment of three noninvasive colorectal cancer screening types with two versions that did or did not present respondents with detailed information about the possible invasive follow-up test (i.e., colonoscopy) and its procedure. We used data from 631 Dutch respondents aged 55 to 75 years. Each respondent received only one of the two versions (N = 310 for the invasive follow-up test information specification version, and N = 321 for the no-information specification version). RESULTS: Mixed logit model results show that detailed information about the invasive follow-up test negatively affects screening participation decisions. This effect can be explained mainly by a decrease in choice shares for the most preferred screening test (a combined stool and blood sample test). Choice share simulations based on the discrete choice experiment indicated that presenting invasive follow-up test information decreases screening participation by 4.79%. CONCLUSIONS: Detailed information about the invasive follow-up test has a negative effect on individuals' screening participation decisions in noninvasive colorectal cancer screening campaigns. This result poses new challenges for policymakers who aim not only to increase uptake but also to provide full disclosure to potential screening participants. PMID- 25128052 TI - Should I stay or should I go home? A latent class analysis of a discrete choice experiment on hospital-at-home. AB - OBJECTIVES: This study aimed 1) to quantify the strength of patient preferences for different aspects of early assisted discharge in The Netherlands for patients who were admitted with a chronic obstructive pulmonary disease exacerbation and 2) to illustrate the benefits of latent class modeling of discrete choice data. This technique is rarely used in health economics. METHODS: Respondents made multiple choices between hospital treatment as usual (7 days) and two combinations of hospital admission (3 days) followed by treatment at home. The latter was described by a set of attributes. Hospital treatment was constant across choice sets. Respondents were patients with chronic obstructive pulmonary disease in a randomized controlled trial investigating the cost-effectiveness of early assisted discharge and their informal caregivers. The data were analyzed using mixed logit, generalized multinomial logit, and latent-class conditional logit regression. These methods allow for heterogeneous preferences across groups, but in different ways. RESULTS: Twenty-five percent of the respondents opted for hospital treatment regardless of the description of the early assisted discharge program, and 46% never opted for the hospital. The best model contained four latent classes of respondents, defined by different preferences for the hospital and caregiver burden. Preferences for other attributes were constant across classes. Attributes with the strongest effect on choices were the burden on informal caregivers and co-payments. Except for the number of visits, all attributes had a significant effect on choices in the expected direction. CONCLUSIONS: Considerable segments of respondents had fixed preferences for either treatment option. Applying latent class analysis was essential in quantifying preferences for attributes of early assisted discharge. PMID- 25128053 TI - Chinese time trade-off values for EQ-5D health states. AB - OBJECTIVE: To generate a Chinese general population-based three-level EuroQol five-dimensios (EQ-5D-3L) social value set using the time trade-off method. METHODS: The study sample was drawn from five cities in China: Beijing, Guangzhou, Shenyang, Chengdu, and Nanjing, using a quota sampling method. Utility values for a subset of 97 health states defined by the EQ-5D-3L descriptive system were directly elicited from the study sample using a modified Measurement and Valuation of Health protocol, with each respondent valuing 13 of the health states. The utility values for all 243 EQ-5D-3L health states were estimated on the basis of econometric models at both individual and aggregate levels. Various linear regression models using different model specifications were examined to determine the best model using predefined model selection criteria. RESULTS: The N3 model based on ordinary least square regression at the aggregate level yielded the best model fit, with a mean absolute error of 0.020, 7 and 0 states for which prediction errors were greater than 0.05 and 0.10, respectively, in absolute magnitude. This model passed tests for model misspecification (F = 2.7; P = 0.0509, Ramsey Regression Equation Specification Error Test), heteroskedasticity (chi(2) = 0.97; P = 0.3254, Breusch-Pagan/Cook-Weisberg test), and normality of the residuals (chi(2) = 1.285; P = 0.5259, Jarque-Bera test). The range of the predicted values (-0.149 to 0.887) was similar to those estimated in other countries. CONCLUSIONS: The study successfully developed Chinese utility values for EQ-5D-3L health states using the time trade-off method. It is the first attempt ever to develop a standardized instrument for quantifying quality adjusted life-years in China. PMID- 25128054 TI - The effects of total knee arthroplasty on physical functioning and health among the under age 65 population. AB - OBJECTIVES: This study examined the effects of total knee arthroplasty on six measures of physical functioning, self-rated health, pain, earnings, and employment status among US adults aged 51 to 63 years at baseline. METHODS: Data came from the Health and Retirement Study, a nationally representative longitudinal study conducted biannually. The analysis sample consisted of individuals aged 51 to 63 years at baseline with arthritis who were resurveyed at 2-year intervals from 1996 to 2010. Propensity score matching was used to compare outcomes of persons receiving total knee arthroplasty (TKA) with those of matched controls. Six measures of physical functioning were examined: lower-body mobility problems, instrumental activities of daily living limitations, activities of daily living limitations, and large muscle, fine motor, and gross motor limitations. Self-rated health and pain were also examined. The two employment related outcomes were earnings and employment status. RESULTS: Receipt of TKA was associated with better outcomes for several measures of physical functioning, especially mobility limitations, pain, and self-rated health. Receipt of TKA was not associated with increased earnings or employment. CONCLUSIONS: Receipt of TKA yields important improvements in physical function among persons with an arthritis diagnosis who received the procedure before reaching the age of 65 years. This study contributes to knowledge about the benefits of TKA in a community setting among nonelderly recipients of TKA. PMID- 25128056 TI - Two approaches to incorporate clinical data uncertainty into multiple criteria decision analysis for benefit-risk assessment of medicinal products. AB - BACKGROUND: The Problem formulation, Objectives, Alternatives, Consequences, Trade-offs, Uncertainties, Risk attitude, and Linked decisions (PrOACT-URL) framework and multiple criteria decision analysis (MCDA) have been recommended by the European Medicines Agency for structured benefit-risk assessment of medicinal products undergoing regulatory review. OBJECTIVE: The objective of this article was to provide solutions to incorporate the uncertainty from clinical data into the MCDA model when evaluating the overall benefit-risk profiles among different treatment options. METHODS: Two statistical approaches, the delta-method approach and the Monte-Carlo approach, were proposed to construct the confidence interval of the overall benefit-risk score from the MCDA model as well as other probabilistic measures for comparing the benefit-risk profiles between treatment options. Both approaches can incorporate the correlation structure between clinical parameters (criteria) in the MCDA model and are straightforward to implement. RESULTS: The two proposed approaches were applied to a case study to evaluate the benefit-risk profile of an add-on therapy for rheumatoid arthritis (drug X) relative to placebo. It demonstrated a straightforward way to quantify the impact of the uncertainty from clinical data to the benefit-risk assessment and enabled statistical inference on evaluating the overall benefit-risk profiles among different treatment options. CONCLUSIONS: The delta-method approach provides a closed form to quantify the variability of the overall benefit-risk score in the MCDA model, whereas the Monte-Carlo approach is more computationally intensive but can yield its true sampling distribution for statistical inference. The obtained confidence intervals and other probabilistic measures from the two approaches enhance the benefit-risk decision making of medicinal products. PMID- 25128057 TI - An updated method for risk adjustment in outcomes research. AB - OBJECTIVE: To demonstrate why meta-analytic methods need modification before they can be used to aggregate rates or effect sizes in outcomes research, under the constraint of no common underlying effect or rate. METHODS: Studies are presented that require different types of risk adjustment. First, we demonstrate using rates that external risk adjustment through standardization can be achieved using modified meta-analytic methods, but only with a model that allows input of user defined weights. Next, we extend these observations to internal risk adjustment of comparative effect sizes. RESULTS: We show that this procedure produces identical results to conventional age standardization if a rate is being standardized for age. We also demonstrate that risk adjustment of effect sizes can be achieved with this modified method but cannot be done using standard meta analysis. CONCLUSIONS: We conclude that this method allows risk adjustment to be performed in situations in which currently the fixed- or random-effects methods of meta-analysis are inappropriately used. The latter should be avoided when the underlying aim is risk adjustment rather than meta-analysis. PMID- 25128055 TI - Physician social networks and variation in rates of complications after radical prostatectomy. AB - OBJECTIVES: Variation in care within and across geographic areas remains poorly understood. The goal of this article was to examine whether physician social networks-as defined by shared patients-are associated with rates of complications after radical prostatectomy. METHODS: In five cities, we constructed networks of physicians on the basis of their shared patients in 2004-2005 Surveillance, Epidemiology and End Results-Medicare data. From these networks, we identified subgroups of urologists who most frequently shared patients with one another. Among men with localized prostate cancer who underwent radical prostatectomy, we used multilevel analysis with generalized linear mixed-effect models to examine whether physician network structure-along with specific characteristics of the network subgroups-was associated with rates of 30-day and late urinary complications, and long-term incontinence after accounting for patient-level sociodemographic, clinical factors, and urologist patient volume. RESULTS: Networks included 2677 men in five cities who underwent radical prostatectomy. The unadjusted rate of 30-day surgical complications varied across network subgroups from an 18.8 percentage-point difference in the rate of complications across network subgroups in city 1 to a 26.9 percentage-point difference in city 5. Large differences in unadjusted rates of late urinary complications and long term incontinence across subgroups were similarly found. Network subgroup characteristics-average urologist centrality and patient racial composition-were significantly associated with rates of surgical complications. CONCLUSIONS: Analysis of physician networks using Surveillance, Epidemiology and End Results Medicare data provides insight into observed variation in rates of complications for localized prostate cancer. If validated, such approaches may be used to target future quality improvement interventions. PMID- 25128058 TI - Improving the contribution of regulatory assessment reports to health technology assessments--a collaboration between the European Medicines Agency and the European network for Health Technology Assessment. AB - In response to a recommendation from the Pharmaceutical Forum, the European Medicines Agency and the European network for Health Technology Assessment initiated a collaboration with the aim to improve the contribution regulatory assessment reports can make to the assessment of relative effectiveness of medicinal products by health technology assessment bodies. This collaboration on improving European Public Assessment Reports (EPARs) started in February 2010 and was performed over 2 years. As a result, the templates for preparing EPARs were revised to better address the needs of heath technology organizations. The better understanding of information needs was a key outcome of the collaboration. To ascertain whether these template changes led to the inclusion of relevant information, a review of a small set of EPARs for recently approved medicinal products was carried out in parallel by both the European network for Health Technology Assessment and the European Medicines Agency. This report provides an account of this project on improving EPARs, which is part of the ongoing dialogue between regulators and health technology assessment bodies on a European level to support policymaker decisions in the future. PMID- 25128059 TI - A comparison of national guidelines for network meta-analysis. AB - OBJECTIVES: Within technology appraisals, it is necessary to compare the complete set of treatments that may be used in the patient group under consideration. Randomized controlled trials are a key source of evidence for these comparisons. The techniques of network meta-analysis allow the networks of trial evidence to be evaluated to obtain estimates of comparative efficacy between sets of treatments. These techniques may be the only source of estimates of comparative effectiveness if trials directly comparing the treatments of interest have not been conducted, and may provide useful additional evidence if both direct and indirect comparisons exist. METHODS: We examined both published and draft guidelines from reimbursement and health technology appraisal bodies, and considered their recommendations using appropriate methodology for the conduct of indirect comparisons and the assessments of their validity. RESULTS: Guidelines from 33 countries were reviewed. Of these, guidelines from 9 countries-Australia, Belgium, Canada, France, Germany, Scotland, Spain, South Africa, and the United Kingdom (England and Wales)-included detailed recommendations on the conduct of network meta-analysis. The recommendations were summarized. CONCLUSIONS: No two recommendations from the multiple national guidelines are mutually exclusive. It is possible to perform one network meta-analysis for submission to multiple national jurisdictions. PMID- 25128060 TI - Cognitive overload? An exploration of the potential impact of cognitive functioning in discrete choice experiments with older people in health care. AB - OBJECTIVES: This exploratory study sought to investigate the effect of cognitive functioning on the consistency of individual responses to a discrete choice experiment (DCE) study conducted exclusively with older people. METHODS: A DCE to investigate preferences for multidisciplinary rehabilitation was administered to a consenting sample of older patients (aged 65 years and older) after surgery to repair a fractured hip (N = 84). Conditional logit, mixed logit, heteroscedastic conditional logit, and generalized multinomial logit regression models were used to analyze the DCE data and to explore the relationship between the level of cognitive functioning (specifically the absence or presence of mild cognitive impairment as assessed by the Mini-Mental State Examination) and preference and scale heterogeneity. RESULTS: Both the heteroscedastic conditional logit and generalized multinomial logit models indicated that the presence of mild cognitive impairment did not have a significant effect on the consistency of responses to the DCE. CONCLUSIONS: This study provides important preliminary evidence relating to the effect of mild cognitive impairment on DCE responses for older people. It is important that further research be conducted in larger samples and more diverse populations to further substantiate the findings from this exploratory study and to assess the practicality and validity of the DCE approach with populations of older people. PMID- 25128061 TI - LEF1 regulates glioblastoma cell proliferation, migration, invasion, and cancer stem-like cell self-renewal. AB - Glioblastoma multiforme (GBM; WHO grade IV) is one of the most common primary tumors of the central nervous system. This disease remains one of the incurable human malignancies because the molecular mechanism driving the GBM development and recurrence is still largely unknown. Here, we show that knockdown of lymphocyte enhancer factor-1 (LEF1), a major transcription factor of Wnt pathway, inhibits U251 cell migration, invasion, and proliferation. Furthermore, downregulation of LEF1 expression inhibits the self-renewal capacity of U251 GBM stem-like cells and decreases the expression level of the GBM stem-like cell (GSC) markers such as CD133 and nestin. Our findings reveal that LEF1 maintains the GBM cell proliferation, migration, and GBM stem-like cell self-renewal. Taken together, these results suggest that LEF1 may be a novel therapeutic target for GBM suppression. PMID- 25128062 TI - Over-expression of TRPM8 is associated with poor prognosis in urothelial carcinoma of bladder. AB - Transient receptor protein (TRP) channels are frequently associated with tumors and are correlated to patient's outcome. We firstly investigated TRP channel melastatin 8 (TRPM8) expression in urothelial carcinoma of bladder (UCB) and its correlation with UCB clinicopathological features and additionally evaluated the association between TRPM8 expression and patients' survival rate to elucidate its role in bladder oncogenesis. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was conducted to examine TRPM8 messenger RNA (mRNA) expression in 36 pairs of freshly frozen UCB tissues and matched noncancerous tissues. Immunohistochemistry (IHC) was performed in 156 archived paraffin-embedded UCB samples to explore the correlation between TRPM8 protein and clinicopathological features. The association between TRPM8 expression and patient's survival rate was evaluated using the Kaplan-Meier method and multivariate Cox regression analysis, respectively. The expression levels of TRPM8 mRNA in UCB tissues were significantly higher than those in matched noncancerous tissues (P=0.016). Expression of TRPM8 protein in UCB was significantly and positively associated with histological grade (P=0.039) and tumor stage (P=0.037). Significant correlation between high TRPM8 expression and poor cumulative survival of UCB patients was shown using the Kaplan-Meier survival curve (P=0.039). TRPM8 was represented as an independent prognostic biomarker for UCB patients by multivariate Cox regression analysis (P=0.047). The present study provide the convincing evidence for the first time that over expression of TRPM8 may play a role in the pathogenesis and progression of UCB, and TRPM8 may serve as an independent prognostic biomarker for UCB patients. PMID- 25128063 TI - Lin28 promotes Her2 expression and Lin28/Her2 predicts poorer survival in gastric cancer. AB - The main purpose of this study is to investigate the interactions between Lin28 and Her2 in gastric cancer. Lin28 and Her2 expression were evaluated in surgically resected samples of 298 gastric cancer patients using immunohistochemical staining. The correlations between Lin28/Her2 expression and clinical variables were retrospectively analyzed. The mRNA level of LIN28 and HER2 was detected by reverse-transcriptase polymerase chain reaction. Among all gastric cancer patients, 33.9% (101/298) were determined as Her2-positive, and 43.0% (128/298) were defined as Lin28-positive. Lin28 was significantly associated with Her2, advanced tumor stage, lesion size, and Ki67 level (p<0.05 for each). Kaplan-Meier analysis illustrated that both Lin28 and Her2 are poor prognostic factors in gastric cancer; Lin28(+)/Her2(+) patients have the poorest survival (median survival = 17 months, p<0.01). Multivariate Cox analysis showed that Lin28 is a significant prognostic factor (hazard ratio (HR) = 1.79, 95% confidence interval (CI) 1.23-2.62). Further stratification analysis indicated that Lin28 may be a prognostic factor in chemotherapy. In vitro data on MKN-28 and MKN-45 cells showed that Lin28 can upregulate Her2 expression at translational level. Both Lin28 and Her2 are poor prognostic factors in gastric cancer. Lin28 may regulate Her2 post-transcriptionally in gastric cancer cells, which indicates it might be a potential target in the treatment of gastric cancer. PMID- 25128064 TI - Designing a recombinant chimeric construct contain MUC1 and HER2 extracellular domain for prediagnostic breast cancer. AB - Breast cancer is the most common cancer among women in the world. One of the approaches for diagnosis of breast cancer is detection of its tumor-associated markers. Mucin 1 (MUC1), a tumor-associated antigen, is a transmembrane glycoprotein expressed by normal epithelial cells and overexpressed by carcinomas of epithelial origin. Also, human epidermal growth factor receptor-2 (HER2/erbB 2) belongs to the one of four members of tyrosin kinase type 1 family in which overexpression of HER2 is associated with malignancy in breast cancer. This study was aimed to bioinformatics analysis and designing a recombinant chimeric protein containing MUC1 and HER2 antigens to express in prokaryotic host (Escherichia coli) as breast cancer diagnosis tools. The immunogenic sequences of MUC1 and HER2 were extracted and fused together by a linker. The chimeric construct was analyzed by bioinformatics softwares. The optimization and purification, evaluation of the expression of chimeric protein was performed using Western blotting, ELISA, and immunohistochemistry. The results showed that the chimeric construct was stable and immunogenic domains were exposed. The pET-28a vector containing chimeric gene had high level of protein expression. The recombinant chimeric protein was confirmed using Western blotting, and it was investigated using ELISA and IHC. Then, the MUC1 and HER2 combined peptides can be used as coating antigens in ELISA for detection of antibodies against MUC1 or HER2 in human serum. PMID- 25128065 TI - Apoptotic effect of genistein on human colon cancer cells via inhibiting the nuclear factor-kappa B (NF-kappaB) pathway. AB - Genistein possesses a wide variety of biological activities, and it is best known for its ability to inhibit cancer progression. Its cancer-preventive effect has been attributed to various mechanisms, including the induction of cell cycle arrest and apoptosis as well as the antioxidant functions. Nuclear factor kappa-B (NF-kappaB) is a signaling pathway that controls transcriptional activation of genes important for the tight regulation of many cellular processes and is aberrantly expressed in many types of cancer. Inhibitors of NF-kappaB pathway have shown potential anti-tumor activities. However, it is not fully elucidated in colon cancer. In the present study, we demonstrated that genistein could induce apoptosis in human colon cancer LoVo and HT-29 cells through inhibiting NF kappaB pathway, as well as downregulation of Bcl-2 and upregulation of Bax, thus providing basis for clinical application of genistein in colon cancer cases. PMID- 25128068 TI - A randomized controlled clinical trial of formalin for treatment of chronic hemorrhagic radiation proctopathy in cervical carcinoma patients. AB - PURPOSE: Chronic hemorrhagic radiation proctopathy is not uncommon after radiotherapy for cervical carcinoma. The outcomes of several treatments have been variable. Many studies demonstrate that topical treatment with 4 % formalin is effective and safe. However, a nonrandomized control study showed a high response rate and good tolerance in chronic radiation proctopathy patients treated with 10 % formalin. The optimal concentration of formalin therefore remains unclear. METHODS: To compare the effectiveness and safety of 4 and 10 % formalin for the treatment of chronic hemorrhagic radiation proctopathy, a prospective trial was conducted at the Department of Gynecology of the Affiliated Hospital of Binzhou Medical College from January 2009 to December 2012. One hundred and twenty patients with chronic hemorrhagic radiation proctopathy following radiotherapy for cervical carcinoma were recruited and randomized to receive 4 or 10 % formalin. A standard protocol was followed for formalin application. Symptom and rectoscopy scores were evaluated before and at 12 weeks after treatment. RESULTS: In the 4 % formalin group, 49 (86.0 %) and 53 (91.4 %) patients showed an improvement in symptom score and rectoscopy score, respectively (P = 0.36). Symptom and rectoscopy scores decreased significantly after treatment in both the 4 % formalin group and the 10 % formalin group (P < 0.001). Symptom score was correlated with rectoscopy score (P < 0.001). More patients in the 10 % group suffered treatment-related complications than did those in the 4 % group (P = 0.03). CONCLUSIONS: For the treatment of chronic hemorrhagic radiation proctopathy, 4 % should be the preferred formalin concentration. PMID- 25128067 TI - Musculoskeletal pain and health-related quality of life among breast cancer patients treated with aromatase inhibitors. AB - OBJECTIVE: This study aims to examine the associations between musculoskeletal pain and health-related quality of life (HR-QOL) among breast cancer patients on aromatase inhibitors (AIs) and women without a history of breast cancer. METHODS: A cross-sectional study was conducted among 68 breast cancer patients on AIs for an average of 3.5 years and 137 postmenopausal women without a history of cancer. Musculoskeletal pain was assessed using a 10-cm visual analog scale; HR-QOL was examined using the Medical Outcomes Study Short Form (SF-36) health survey. Linear regression was used to estimate the associations between pain and HR-QOL in both groups. RESULTS: Approximately 64 % of the breast cancer patients and women in the comparison group reported musculoskeletal pain. Among women with breast cancer, those with pain had significantly lower HR-QOL scores in the physical (52.2 vs. 42.6; p < 0.001) and mental (52.7 vs. 45.5; p = 0.01) component summary scores compared with those without pain. In the comparison group, pain was associated with significantly lower scores in the physical (55.4 vs. 46.0; p < 0.001), but not the mental, component summary score (52.1 vs. 52.4; p = 0.82). The significant associations between pain and HR-QOL persisted after confounder adjustment in both groups. Among women with similar severity of pain, breast cancer patients reported significantly lower HR-QOL in the mental summary component compared with the women in the comparison group. CONCLUSIONS: Among breast cancer patients, musculoskeletal pain adversely affects both mental and physical components of HR-QOL. Preventing or treating AI-associated musculoskeletal pain may improve overall HR-QOL among breast cancer patients treated with AIs. PMID- 25128070 TI - Mesenchymal stem cells in lung cancer tumor microenvironment: their biological properties, influence on tumor growth and therapeutic implications. AB - The tumor microenvironment (TME) of lung cancer has been documented to play an important role in participating in tumor disease progression. As the precursor of most stroma in TME, mesenchymal stem cells (MSCs) draw great attention since evidence has suggested that MSCs derived from lung cancer patients present a different phenotype compared to their normal counterparts. Furthermore, MSCs could be recruited towards tumor sites and influence tumor survival, although the effect remains contradictory. Our review will summarize the current advance of the role MSCs in lung cancer and explore the possible treatment strategies by blocking their crosstalk. PMID- 25128069 TI - Transcription factor OCT4 promotes cell cycle progression by regulating CCND1 expression in esophageal carcinoma. AB - The CCND1 gene is overexpressed in esophageal cancer and accelerates cell cycle progression. However, the mechanism whereby the upstream genes or factors directly regulate CCND1 expression remains unknown. By analyzing the 5'-UTR region of the CCND1 gene, we found that this region contains an octamer motif (ATTTTGCAT), which suggests that the expression of CCND1 might be directly associated with octamer-binding transcription factor 4 (OCT4). In this study, the wild-type and the octamer motif-mutanted CCND1 promoters were cloned, and their corresponding luciferase reporter vectors were then constructed to study the molecular mechanism by which OCT4 regulates the expression of CCND1 and influences the biological behaviors of esophageal cancer cells. The results indicated that suppressing the expression of CCND1 and OCT4 in esophageal cancer cells reduced cell proliferative and invasive abilities, induced cell cycle G1 phase arrest, and slowed the growth of xenografts in nude mice. Suppression of OCT4 expression significantly decreased the wild-type CCND1 promoter activity and down-regulated the expression of CCND1, but did not affect the activity of the mutant promoter. Whereas, suppression of CCND1 did not affect OCT4 expression, suggesting that OCT4 regulates CCND1 expression by activating the CCND1 promoter and subsequently promoting cell cycle progression. The results revealed and confirmed that OCT4 is the upstream factor that directly binds to the CCND1 promoter to regulate CCND1 expression, then to promote cell cycle progression and accelerate the proliferation and invasion of esophageal cancer cells. This finding may significantly contribute to elucidating the regulatory mechanism involved in the cell cycle progression of esophageal cancer cells and may aid in screening potential gene targets for the biological therapy of esophageal cancer. PMID- 25128071 TI - The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in vitro and in vivo. AB - Supranutritional selenite has anti-cancer therapeutic effects in vivo; however, the detailed mechanisms underlying these effects are not clearly understood. Further studies would broaden our understanding of the anti-cancer effects of this compound and provide a theoretical basis for its clinical application. In this study, we primarily found that selenite exposure inhibited phosphorylation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), leading to suppression of Bcl-2 in HCT116 and SW480 colorectal cancer (CRC) cells. Moreover, the selenite-induced inhibitory effect on PKD1 activation was involved in suppression of the CREB signalling pathway. Additionally, we discovered that selenite treatment can upregulate p38 MAPK phosphorylation, which results in inhibition of the PKD1/CREB/Bcl-2 survival pathway and triggers apoptosis. Finally, we established a colorectal cancer xenograft model and found that selenite treatment markedly inhibits tumour growth through the MAPK/PKD1/CREB/Bcl-2 pathway in vivo. Our results demonstrated that a supranutritional dose of selenite induced CRC cell apoptosis through inhibition of the PKD1/CREB/Bcl-2 axis both in vitro and in vivo. PMID- 25128072 TI - Increased cardiovascular disease mortality associated with excessive exercise in heart attack survivors. AB - OBJECTIVE: To test whether greater exercise is associated with progressively lower mortality after a cardiac event. PATIENTS AND METHODS: We used Cox proportional hazard analyses to examine mortality vs estimated energy expended by running or walking measured as metabolic equivalents (3.5 mL O2/kg per min per day or metabolic equivalent of task-h/d [MET-h/d]) in 2377 self-identified heart attack survivors, where 1 MET-h/d is the energy equivalent of running 1 km/d. Mortality surveillance via the National Death Index included January 1991 through December 2008. RESULTS: A total of 526 deaths occurred during an average prospective follow-up of 10.4 years, 376 (71.5%) of which were related to cardiovascular disease (CVD) (International Statistical Classification of Diseases, 10th Revision codes I00-I99). CVD-related mortality compared with the lowest exercise group decreased by 21% for 1.07 to 1.8 MET-h/d of running or walking (P=.11), 24% for 1.8 to 3.6 MET-h/d (P=.04), 50% for 3.6 to 5.4 MET-h/d (P=.001), and 63% for 5.4 to 7.2 MET-h/d (P<.001) but decreased only 12% for >=7.2 MET-h/d (P=.68). These data represent a 15% average risk reduction per MET h/d for CVD-related mortality through 7.2 MET-h/d (P<.001) and a 2.6-fold risk increase above 7.2 MET-h/d (P=.009). Relative to the risk reduction at 7.2 MET h/d, the risk for >=7.2 MET-h/d increased 3.2-fold (P=.006) for all ischemic heart disease (IHD)-related mortalities but was not significantly increased for non-IHD-CVD, arrhythmia-related CVD, or non-CVD-related mortalities. CONCLUSION: Running or walking decreases CVD mortality risk progressively at most levels of exercise in patients after a cardiac event, but the benefit of exercise on CVD mortality and IHD deaths is attenuated at the highest levels of exercise (running: above 7.1 km/d or walking briskly: 10.7 km/d). PMID- 25128073 TI - Exercising for health and longevity vs peak performance: different regimens for different goals. PMID- 25128074 TI - Elite athletes live longer than the general population: a meta-analysis. AB - OBJECTIVE: To perform a meta-analysis of cohort studies aimed at providing an accurate overview of mortality in elite athletes. PATIENTS AND METHODS: We reviewed English-language scientific articles available in Medline and Web of Science databases following the recommendations of the Meta-analyses Of Observational Studies in Epidemiology group. We searched for publications on longevity and professional or elite athletes (with no restriction on the starting date and up to March 31, 2014). RESULTS: Ten studies, including data from a total of 42,807 athletes (707 women), met all inclusion criteria. The all-cause pooled standard mortality ratio (SMR) was 0.67 (95% CI, 0.55-0.81; P<.001) with no evidence of publication bias (P=.24) but with significant heterogeneity among studies (I(2)=96%; Q=224.46; P<.001). Six studies provided data on cardiovascular disease (CVD) and 5 on cancer (in a total of 35,920 and 12,119 athletes, respectively). When only CVD was considered as a cause of mortality, the pooled SMR was 0.73 (95% CI, 0.65-0.82; P<.001) with no evidence of bias (P=.68) or heterogenity among studies (I(2)=38%; Q=8.07; P=.15). The SMR for cancer was 0.60 (95% CI, 0.38-0.94; P=.03) with no evidence of bias (P=.20) despite a significant heterogeneity (I(2)=91%; Q=44.21; P<.001). CONCLUSION: The evidence available indicates that top-level athletes live longer than the general population and have a lower risk of 2 major causes of mortality, namely, CVD and cancer. PMID- 25128075 TI - Strategy to address innovative off-label medication use in China: grading management. PMID- 25128076 TI - Effects of "Fit fOR The Aged" (FORTA) on pharmacotherapy and clinical endpoints- a pilot randomized controlled study. AB - PURPOSE: The feasibility of applying the Fit fOR The Aged (FORTA) list, a drug classification combining positive and negative labeling of drugs, should be studied in geriatric patients and medication quality and clinical endpoints measured. FORTA labels range from A (indispensable), B (beneficial), C (questionable) to D (avoid). METHODS: A prospective randomized controlled pilot trial was performed in hospitalized geriatric patients in whom the FORTA instrument or standard care was applied. Patients were randomly admitted to an intervention and a control ward. Changes of FORTA label distributions between admission and discharge, over- and under-prescription rates, clinical endpoints including the number of falls during the hospitalization, and Barthel Index (BI) at admission and discharge were measured. RESULTS: Polypharmacy persisted in both groups. At discharge, a higher rate of A drugs was prescribed in the intervention group (58 patients, median age 84 years) vs. standard care (56 patients, median age 83 years, p < 0.02), and both over- and under-prescriptions were significantly lower in the FORTA than in the control group (p < 0.03). Two (3.4%) intervention, but 12 (21.4%) control, patients fell at least once (p < 0.001). The fall rate per 1,000 patient years was 1.5 +/- 8.3 in the intervention and 10.6 +/- 25.4 in the control group (p < 0.004). CONCLUSIONS: This pilot study shows that the application of the FORTA list is feasible in geriatric patients. In this small study, the medication quality improved in the intervention group, but polypharmacy persisted in both groups. The fall rate was significantly lower in the intervention group. These encouraging results must be interpreted carefully. PMID- 25128077 TI - Coexistence of neurofibroma and meningioma at exactly the same level of the cervical spine. AB - We report a case of the coexistence of different spinal tumors at the same level of the cervical spine, without neurofibromatosis (NF), which was successfully treated with surgery. A 72-year-old female presented with right upper-limb clumsiness and weakness. Magnetic resonance imaging revealed an intradural, extramedullary tumor mass at the right C3-4 level with extradural extension into the intervertebral foramen. The extradural tumor was removed, and the pathology showed neurofibroma. After incision of the dura, the intradural tumor was removed, and was identified as meningioma in the pathological report. The patient did not meet the criteria of NF. Coexistence of neurofibroma and meningioma at exactly the same level of the spine without NF is extremely rare. Exploration of the intradural space may be necessary after resection of an extradural tumor if the surgical finding does not correlate well with the preoperative images. PMID- 25128078 TI - Stents in paediatric and adult congenital interventional cardiac catheterization. AB - A 'stent' is a tubular meshed endoprosthesis that has contributed to the development of interventional catheterization over the past 30 years. In congenital heart diseases, stents have offered new solutions to the treatment of congenital vessel stenosis or postsurgical lesions, to maintain or close shunt patency, and to allow transcatheter valve replacement. First, stents were made of bare metal. Then, stent frameworks evolved to achieve a better compromise between radial strength and flexibility. However, almost all stents used currently in children have not been approved for vascular lesions in children and are therefore used 'off-label'. Furthermore, the inability of stents to follow natural vessel growth still limits their use in low-weight children and infants. Recently, bioresorbable stents have been manufactured and may overcome this issue; they are made from materials that may dissolve or be absorbed in the body. In this review, we aim to describe the history of stent development, the technical characteristics of stents used currently, the clinical applications and results, and the latest technological developments and perspectives in paediatric and adult congenital cardiac catheterization. PMID- 25128079 TI - First report on intraoperative vector flow imaging of the heart among patients with healthy and diseased aortic valves. AB - The vector velocity method Transverse Oscillation (TO) implemented on a conventional ultrasound (US) scanner (ProFocus, BK Medical, Herlev, Denmark) can provide real-time, angle-independent estimates of the cardiac blood flow. During cardiac surgery, epicardial US examination using TO was performed on (A) 3 patients with healthy aortic valve and (B) 3 patients with aortic valve stenosis. In group B, the systolic flow of the ascending aorta had higher velocities, was more aliased and chaotic. The jet narrowed to 44% of the lumen compared to 75% in group A and with a vector concentration, a measure of flow complexity, of 0.41 compared to 0.87 in group A. The two groups had similar secondary flow of the ascending aorta with an average rotation frequency of 4.8 Hz. Simultaneous measurements were obtained with spectral Doppler (SD) and a thermodilution technique (TD). The mean difference in peak systolic velocity compared to SD in group A was 22% and 45% in B, while the mean difference in volume flow compared to TD in group A was 30% and 32% in B. TO can potentially reveal new information of cardiac blood flow, and may become a valuable diagnostic tool in the evaluation of patients with cardiovascular diseases. PMID- 25128080 TI - Dentin-smear remains at self-etch adhesive interface. AB - OBJECTIVE: The bonding potential of 'mild' self-etch adhesives may be compromised due to smear interference, as they may not dissolve/penetrate the smear layer effectively due to their relatively low acidity. We observed that the thickness of the dentin smear layer differed depending on the surface-preparation methodology used. METHODS: The interaction of an (ultra-)mild self-etch adhesive (Clearfil S3 Bond, Kuraray Noritake) with human dentin, prepared either using a medium-grit diamond bur ('thick', clinically relevant smear layer) or 600-grit SiC-paper ('thin' smear layer), or just fractured (smear-free), was evaluated using high-resolution transmission electron microscopy (TEM). Non demineralized/demineralized 30-100nm interfacial cross-sections were prepared following common TEM-specimen processing and diamond-knife ultra-microtomy. RESULTS: The adhesive did not dissolve the bur-cut, nor the SiC-ground smear layer, but impregnated it. Within this 'resin-smear complex', hydroxyapatite was abundantly present. At fractured dentin, this complex was not present, while the actual layer of interaction of the adhesive was limited to about 100nm. Non demineralized 'ultra-thin' (30-50nm) sections confirmed the interfacial ultra structure to differ for the three surface-preparation methods. An electron dense band was consistently disclosed at the adhesive interface, most likely representing the documented chemical interaction of the functional monomer 10-MDP with Ca. SIGNIFICANCE: The dentin surface-preparation method significantly affects the nature of the smear layer and the interaction with the ultra-mild self-etch adhesive. PMID- 25128081 TI - Detection of the Helicobacter pylori dupA gene is strongly affected by the PCR design. AB - The Helicobacter pylori virulence gene dupA is usually detected by PCR, but the primer binding sites used are highly variable. Our newly designed qPCR against a conserved region of dupA was positive in 64.2% of 394 clinical isolates while the positivity rate of the commonly used PCRs ranged from 29.9% to 37.8%. PMID- 25128082 TI - A tagged parathyroid hormone derivative as a carrier of antibody cargoes transported by the G protein coupled PTH1 receptor. AB - Based on the known fact that the parathyroid hormone (PTH) might be extended at its C-terminus with biotechnological protein cargoes, a vector directing the secretion of PTH1-84 C-terminally fused with the antigenic epitope myc (PTH-myc) was exploited. The functional properties and potential of this analog for imaging PTH1R-expressing cells were examined. The PTH-myc construct was recombinantly produced as a conditioned medium (CM) of transfected HEK 293a cells (typical concentrations of 187nM estimated with ELISAs for PTH). PTH-myc CM induced cyclic AMP formations (10min), with a minor loss of potency relative to authentic PTH1 84, and c-Fos expression (1-3h). Treatment of recipient HEK 293a cells transiently expressing PTH1R with PTH-myc CM (supplemented with a fluorescent monoclonal anti-myc tag antibody, either 4A6 or 9E10) allowed the labeling of endosomal structures positive for Rab5 and/or for beta-arrestin1 (microscopy, cytofluorometry). Authentic PTH was inactive in this respect, ruling out a non specific form of endocytosis like pinocytosis. Using a horseradish peroxidase conjugated secondary antibody, the endocytosis of the PTH-myc-based antibody complex by endogenous PTH1R was evidenced in MG-63 osteoblastoid cells. The secreted construct PTH-myc represents a bona fide agonist that supports the feasibility of transporting cargoes of considerable molecular weight inside cells using arrestin and Rab5-mediated PTH1R endocytosis. PTH-myc is also transported into cells that express PTH1R at a physiological level. Such tagged peptide hormones may be part of a cancer chemotherapy scheme exploiting a modular cytotoxic secondary antibody and the receptor repertoire expressed in a given tumor. PMID- 25128083 TI - DEK oncogene expression during normal hematopoiesis and in Acute Myeloid Leukemia (AML). AB - DEK is important in regulating cellular processes including proliferation, differentiation and maintenance of stem cell phenotype. The translocation t(6;9) in Acute Myeloid Leukemia (AML), which fuses DEK with NUP214, confers a poor prognosis and a higher risk of relapse. The over-expression of DEK in AML has been reported, but different studies have shown diminished levels in pediatric and promyelocytic leukemias. This study has characterized DEK expression, in silico, using a large multi-center cohort of leukemic and normal control cases. Overall, DEK was under-expressed in AML compared to normal bone marrow (NBM). Studying specific subtypes of AML confirmed either no significant change or a significant reduction in DEK expression compared to NBM. Importantly, the similarity of DEK expression between AML and NBM was confirmed using immunohistochemistry analysis of tissue mircorarrays. In addition, stratification of AML patients based on median DEK expression levels indicated that DEK showed no effect on the overall survival of patients. DEK expression during normal hematopoiesis did reveal a relationship with specific cell types implicating a distinct function during myeloid differentiation. Whilst DEK may play a potential role in hematopoiesis, it remains to be established whether it is important for leukemagenesis, except when involved in the t(6;9) translocation. PMID- 25128085 TI - Nonlinear behaviour of conduction and block in cardiac tissue with heterogeneous expression of connexin 43. AB - Altered gap junctional coupling potentiates slow conduction and arrhythmias. To better understand how heterogeneous connexin expression affects conduction at the cellular scale, we investigated conduction in tissue consisting of two cardiomyocyte populations expressing different connexin levels. Conduction was mapped using microelectrode arrays in cultured strands of foetal murine ventricular myocytes with predefined contents of connexin 43 knockout (Cx43KO) cells. Corresponding computer simulations were run in randomly generated two dimensional tissues mimicking the cellular architecture of the strands. In the cultures, the relationship between conduction velocity (CV) and Cx43KO cell content was nonlinear. CV first decreased significantly when Cx43KO content was increased from 0 to 50%. When the Cx43KO content was >=60%, CV became comparable to that in 100% Cx43KO strands. Co-culturing Cx43KO and wild-type cells also resulted in significantly more heterogeneous conduction patterns and in frequent conduction blocks. The simulations replicated this behaviour of conduction. For Cx43KO contents of 10-50%, conduction was slowed due to wavefront meandering between Cx43KO cells. For Cx43KO contents >=60%, clusters of remaining wild-type cells acted as electrical loads that impaired conduction. For Cx43KO contents of 40-60%, conduction exhibited fractal characteristics, was prone to block, and was more sensitive to changes in ion currents compared to homogeneous tissue. In conclusion, conduction velocity and stability behave in a nonlinear manner when cardiomyocytes expressing different connexin amounts are combined. This behaviour results from heterogeneous current-to-load relationships at the cellular level. Such behaviour is likely to be arrhythmogenic in various clinical contexts in which gap junctional coupling is heterogeneous. PMID- 25128084 TI - A comparative study on the risks of radiogenic second cancers and cardiac mortality in a set of pediatric medulloblastoma patients treated with photon or proton craniospinal irradiation. AB - PURPOSE: To compare the risks of radiogenic second cancers and cardiac mortality in 17 pediatric medulloblastoma patients treated with passively scattered proton or field-in-field photon craniospinal irradiation (CSI). MATERIAL/METHODS: Standard of care photon or proton CSI treatment plans were created for all 17 patients in a commercial treatment planning system (TPS) (Eclipse version 8.9; Varian Medical Systems, Palo Alto, CA) and prescription dose was 23.4 or 23.4 Gy (RBE) to the age specific target volume at 1.8 Gy/fraction. The therapeutic doses from proton and photon CSI plans were estimated from TPS. Stray radiation doses were determined from Monte Carlo simulations for proton CSI and from measurements and TPS for photon CSI. The Biological Effects of Ionization Radiation VII report and a linear model based on childhood cancer survivor data were used for risk predictions of second cancer and cardiac mortality, respectively. RESULTS: The ratios of lifetime attributable risk (RLARs) (proton/photon) ranged from 0.10 to 0.22 for second cancer incidence and ranged from 0.20 to 0.53 for second cancer mortality, respectively. The ratio of relative risk (RRR) (proton/photon) of cardiac mortality ranged from 0.12 to 0.24. The RLARs of both cancer incidence and mortality decreased with patient's age at exposure (e), while the RRRs of cardiac mortality increased with e. Girls had a significantly higher RLAR of cancer mortality than boys. CONCLUSION: Passively scattered proton CSI provides superior predicted outcomes by conferring lower predicted risks of second cancer and cardiac mortality than field-in-field photon CSI for all medulloblastoma patients in a large clinically representative sample in the United States, but the magnitude of superiority depends strongly on the patients' anatomical development status. PMID- 25128086 TI - Caveolin-1 deletion exacerbates cardiac interstitial fibrosis by promoting M2 macrophage activation in mice after myocardial infarction. AB - Adverse remodeling following myocardial infarction (MI) leading to heart failure is driven by an imbalanced resolution of inflammation. The macrophage cell is an important control of post-MI inflammation, as macrophage subtypes secrete mediators to either promote inflammation and extend injury (M1 phenotype) or suppress inflammation and promote scar formation (M2 phenotype). We have previously shown that the absence of caveolin-1 (Cav1), a membrane scaffolding protein, is associated with adverse cardiac remodeling in mice, but the mechanisms responsible remain to be elucidated. We explore here the role of Cav1 in the activation of macrophages using wild type C57BL6/J (WT) and Cav1(tm1Mls/J) (Cav1(-/-)) mice. By echocardiography, cardiac function was comparable between WT and Cav1(-/-) mice at 3days post-MI. In the absence of Cav1, there were a surprisingly higher percentage of M2 macrophages (arginase-1 positive) detected in the infarcted zone. Conversely, restoring Cav1 function after MI in WT mice by adding back the Cav1 scaffolding domain reduced the M2 activation profile. Further, adoptive transfer of Cav1 null macrophages into WT mice on d3 post-MI exacerbated adverse cardiac remodeling at d14 post-MI. In vitro studies revealed that Cav1 null macrophages had a more pronounced M2 profile activation in response to IL-4 stimulation. In conclusion, Cav1 deletion promotes an array of maladaptive repair processes after MI, including increased TGF-beta signaling, increased M2 macrophage infiltration and dysregulation of the M1/M2 balance. Our data also suggest that cardiac remodeling can be improved by therapeutic intervention regulating Cav1 function during the inflammatory response phase. PMID- 25128087 TI - SENP5, a SUMO isopeptidase, induces apoptosis and cardiomyopathy. AB - Cardiomyopathy presents a major health issue and is a leading cause of heart failure. Although a subset of familial cardiomyopathy is associated with genetic mutations, over 50% of cardiomyopathy is defined as idiopathic, the mechanisms underlying which are under intensive investigation. SUMO conjugation is a dynamic posttranslational modification that can be readily reversed by the activity of sentrin-specific proteases (SENPs). However, whether SENPs are implicated in heart disease pathophysiology remains unexplored. We observed a significant increase in the level of SENP5, a SUMO isopeptidase, in human idiopathic failing hearts. To reveal whether it plays a role in the pathogenesis of cardiac muscle disorders, we used a gain-of-function approach to overexpress SENP5 in murine cardiomyocytes (SENP5 transgenic, SENP5-Tg). Overexpression of SENP5 led to cardiac dysfunction, accompanied by decreased cardiomyocyte proliferation and elevated apoptosis. The increase in apoptosis preceded other detectable pathological changes, suggesting its causal link to cardiomyopathy. Further examination of SENP5-Tg hearts unveiled a decrease in SUMO attachment to dynamin related protein (Drp1), a factor critical for mitochondrial fission. Correspondingly, the mitochondria of SENP5-Tg hearts at an early developmental stage were significantly larger compared with those in the control hearts, suggesting that desumoylation of Drp1 at least partially accounts for the cardiac phenotypes observed in the SENP5-Tg mice. Finally, overexpression of Bcl2 in SENP5-Tg hearts improved cardiac function of SENP5-Tg mice, further supporting the notion that SENP5 mainly targets mitochondrial function in vivo. Our findings demonstrate an important role of the desumoylation enzyme SENP5 in the development of cardiac muscle disorders, and point to the SUMO conjugation pathway as a potential target in the prevention/treatment of cardiomyopathy. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". PMID- 25128088 TI - Effects of chronic administration of arachidonic acid on lipid profiles and morphology in the skeletal muscles of aged rats. AB - Arachidonic acid (20:4n-6, ARA) is a major component of the cell membrane, whereas ARA-derived eicosanoids are formed when cells are damaged. Aging is associated with an accretion of oxidative stress in skeletal muscles. In this study, we examined the effects of chronic administration (13 weeks) of ARA (240 mg/kg/day) on fatty acid composition, antioxidative status, and morphology of slow (soleus muscles) and fast (extensor digitorum longus muscles; EDL)-twitch muscles in aged rats (21 months old). The level of reactive oxygen species was higher in the EDL of ARA-administered rats than in that of control rats. ARA administration decreased the muscle cell volumes and increased the number of slow myosin heavy chain (MHC)-positive cells in the EDL. The relative content of MHC2X was increased whereas the relative content of MHC2B was decreased in the EDL of ARA-administered rats. These results suggest that ARA deposition in the fast twitch muscle of aged rats reduced cell volume with an increase in oxidative stress. PMID- 25128089 TI - Central venous occlusion mimics carotid cavernous fistula: a case report and review of the literature. AB - A patient presented with signs and symptoms of a left carotid cavernous fistula (CCF). Computed tomography angiography confirmed filling of the cavernous sinus in the arterial phase. Cerebral digital subtraction angiography demonstrated no evidence of CCF. The workup, diagnosis, and treatment of this patient are discussed, and the literature is reviewed. PMID- 25128090 TI - Cosmetic fat augmentation following breast reconstruction: sonographic appearance with cytopathologic correlation. AB - This series presents the history and imaging of patients who had cosmetic fat augmentation following mastectomy and reconstruction. The cases provide the useful reminder that a complete surgical history is essential when assessing the imaging of a post-operative breast patient and that speaking directly with patients can be a critical step in putting together a complete clinical picture and adding value to their care. PMID- 25128091 TI - Cellular immune response in patients with chronic hepatitis B virus infection. AB - Hepatitis, cirrhosis and hepatocellular carcinoma caused by hepatitis B virus (HBV) infection has threatening human health seriously. As HBV is a kind of non cytotoxic virus, host immune response plays a vital role in pathogenesis and clinical outcomes of hepatitis B. Multiple immune cells (e.g., including cytotoxic T lymphocytes, regulatory T cells, natural killer cells, dendritic cells) are important in the immune regulation of HBV infection. Therefore, focusing on the activation states of immune cells may provide new evidences and strategies for determining immune status of HBV infectors, monitoring progression of diseases and predicting efficacy of antiviral treatment. PMID- 25128092 TI - Apoptotic activity and Treg cells in tissue lesions of patients with leprosy. AB - In order to understand the apoptotic response and the participation of Treg cells in the spectral clinical evolution of leprosy, this study evaluated the immunohistochemical expression of caspase-3 and FoxP3 in skin lesions of leprosy patients with the polar forms of the disease. Forty-nine patients with a confirmed diagnosis of the disease were selected, including 27 with the TT form and 22 with the LL form. Quantitative analysis of caspase-3 immunostaining showed a higher expression of this mediator in the LL form (3.409 +/- 0.6517 cells/mm(2); p = 0.0001). Immunostaining for the transcription factor FoxP3 was higher in the LL form (3.891 +/- 0.9294 cells/mm(2); p = 0.0001). A moderate correlation between the two markers was observed in the TT form (r = 0.5214; p = 0.005). It can be concluded that Treg cells and apoptosis play an effective role for the host defense response, inducing mechanisms involved in the activation of cascades that interfere with the control of the immune response and cell homeostasis. PMID- 25128093 TI - Dynamic computed tomography angiography in suspected brain death: a noninvasive biomarker. AB - PURPOSE: Neurologic determination of death or brain death is primarily a clinical diagnosis. This must respect all guarantees required by law and should be determined early to avoid unnecessary treatment and allow organ harvesting for transplantation. Ancillary testing is used in situations in which clinical assessment is impossible or confounded by other factors. Our purpose is to determine the utility of dynamic computed tomographic angiography (dCTA) as an ancillary test for diagnosis of brain death. MATERIALS AND METHODS: We retrospectively reviewed 13 consecutive patients with suspected brain death in the intensive care unit who had dCTA. Contrast appearance timings recorded from the dCTA data were compared to findings from 15 controls selected from patients who presented with symptoms of acute stroke but showed no stroke in follow-up imaging. RESULTS: The dCTA allows us to reliably assess cerebral blood flow and to record time of individual cerebral vessels opacification. It also helps us to assess the intracranial flow qualitatively against the flow in extracranial vessels as a reference. We compared the time difference between enhancement of the external and internal carotid arteries and branches. In all patients who were brain dead, internal carotid artery enhancement was delayed, which occurred after external carotid artery branches were opacified. CONCLUSION: In patients with suspected brain death, dCTA reliably demonstrated the lack of cerebral blood flow, with extracranial circulation as an internal reference. Our initial results suggest that inversion of time of contrast appearance between internal carotid artery and external carotid artery branches at the skull base could predict a lack of distal intracranial flow. PMID- 25128094 TI - Looking back, moving forward: an analysis of complaints submitted to a Canadian tertiary care radiology department and lessons learned. AB - PURPOSE: We present an analysis of various types and strata of complaints received in a geographically isolated tertiary care center over a 2.5-year period. METHODS: Research ethics board approval was obtained. The institution described is a closed system with formalized procedures for submitting complaints. All complaints submitted between November 2010 and March 2013 were collected retrospectively. The following data were extracted: type of complainant, nature of the complaint, site or modality of concern, dates in question, and the response. The data were analysed in multiple subgroups and compared with patient and study volume data. RESULTS: The frequency of complaints equalled 0.01% (100/1,050,000). The largest group of those who submitted complaints were patients (69% [69/100]), followed by referring physicians (16%). Examination scheduling and interpersonal conflicts were equally of greatest frequency of concern (21% [21/100]), followed by issues with study reporting (16%). The average time interval between complaint submission and formal address was 15 days. CONCLUSIONS: We present a low frequency of complaints, with the majority of these complaints submitted by patients; scheduling and personal interactions were most often involved. Effective communication, both with patients and referring physicians, was identified as a particular focus for improving satisfaction. PMID- 25128095 TI - The crosslinking of polysaccharides with polyamines and dextran-polyallylamine antibacterial hydrogels. AB - A facile modular approach to rapidly prepare pH-responsive hydrogels by crosslinking polysaccharides with polyamines is demonstrated. Hydrogels are prepared by first reacting the less reactive polysaccharides with the cross linker epichlorohydrin and completed by the addition of polyamines. The crosslinking of polysaccharides with polyamines provides a facile method for incorporating functionality into polysaccharide based hydrogels. This process is demonstrated with the polysaccharides dextran, pullulan and carboxymethyl cellulose and with the polyamines polyallylamine and polyethylene imine. The hydrogels were characterized by FTIR and swelling studies, which showed pH dependent swelling due to the presence of the polyamine. The hydrogels can also be tailored by varying the mass ratio between the polysaccharide and polyamine. Absorption studies of organic analytes showed the polyamine content affecting the uptake of a charged substrate (methylene blue) and no effect on a neutral substrate (6-methyl coumarin). This synthetic method was also used to prepare hydrogels with antibacterial activity against E. coli and S. aureus by utilizing an amphiphilic polyallylamine. PMID- 25128096 TI - Free-radical scavenging properties and antioxidant activities of botryosphaeran and some other beta-D-glucans. AB - beta-D-Glucans are known to present antitumor, anticancer, and anti-inflammatory activities that are influenced by their own antioxidant capacity. The antioxidant activity of botryosphaeran, an exopolysaccharide of the (1 -> 3;1 -> 6)-beta-D glucan type produced by the Botryosphaeria rhodina MAMB-05 was evaluated and compared to some other beta-D-glucans (lasiodiplodan an exocellular (1 -> 6)-beta D-glucan from Lasiodiplodia theobromae, laminarin and curdlan), and oligosaccharides, disaccharides, and monosaccharides in a study of scavenging activities of free radicals in-vitro. Botryosphaeran displayed high total antioxidant activity (80%) as well as good scavenging activity against hydroxyl radical (90.6%), superoxide anion (37%), hydrogen peroxide (38%), and nitric oxide radical (90%). No reducing power, metal-chelating capacity or inhibition of lipid peroxidation was observed for these beta-D-glucans. The results demonstrated that botryosphaeran exhibited effective antioxidant activity as supported by many different assays, suggesting that this beta-D-glucan may serve as a source of a new bioactive compound with effective antioxidant activity. PMID- 25128097 TI - Production of alpha-amylase for the biosynthesis of gold nanoparticles using Streptomyces sp. MBRC-82. AB - Marine actinobacterial synthesis of gold nanoparticles has good potential to develop simple, cost-effective and eco-friendly methods for production of important biomaterials. In this context, gold nanoparticles have attracted considerable attention in recent years, owing to their various applications. In this paper, we report on the production of alpha-amylase for the extracellular synthesis of gold nanoparticles using Streptomyces sp. MBRC-82. Medium composition and culture conditions for alpha-amylase production were statistically optimized. Plackett-Burman design was employed to find out the optimal medium constituents and culture conditions to enhance alpha-amylase production. Box-Behnken design revealed that three independent variables namely soluble starch (5.8484 g), peptone (3.5191 g), and NaCl (0.3829) significantly influenced alpha-amylase production. The gold nanoparticles were characterized by ultraviolet-visible (UV-vis) spectrometer, X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDXA), and transmission electron microscopy (TEM). The particles synthesized using the optimized enzyme activity ranged from 20 to 80 nm with an average particle size of 40 nm and therefore can be extended to various medicinal applications. PMID- 25128098 TI - New heterocycle modified chitosan adsorbent for metal ions (II) removal from aqueous systems. AB - A new hydrogel based on a modified chitosan CS-B was synthesized and evaluated for its metal ion removal from aqueous systems. The CS-B hydrogel was prepared through modification of chitosan with 4-((1, 3-dioxoisoindolin-2-ylimino) methyl) benzaldehyde as a heterocyclic component. The new hydrogel was analyzed by diverse techniques such as FTIR, XRD, TGA, SEM, and swelling tests. The adsorption capacity of CS-B for metal ions Co(2+), Hg(2+), Cu(2+), Zn(2+), and Pb(2+) from aqueous systems at different pH values showed various levels of efficiency. The metal ion uptake data over a range of pH values for Co(2+) and Hg(2+) showed the highest adsorption capacity while Cu(2+), Zn(2+), and Pb(2+) showed moderate adsorption capacity. Selective metal ion efficiency was highest for Co(2+) and lowest for Hg(2+) in their binary mixture. PMID- 25128099 TI - Identification, characterization, immobilization of a novel type hydrolase (LmH) from Listeria monocytogenes. AB - A novel type of hydrolase (LmH) from Listeria monocytogenes was identified, characterized, and immobilized for biotechnological applications. Primary sequence analysis indicated that LmH had a catalytic triad (Ser(91)-Asp(192) His(222)) with a molecular weight of 27.8 kDa. Homologs of this enzyme are produced by many Gram-positive bacteria including Bacillus, Staphylococcus, and Enterococcus. Biochemical properties of LmH were investigated by performing mass spectrometry, dynamic light scattering (DLS), enzyme assays, enantioselective analysis, circular dichroism (CD) spectroscopy, fluorescence analysis, and macroscopic hydrogel formations. Interestingly, cross-linked enzyme aggregates (CLEAs) of LmH exhibited enhanced stability and good recycling abilities compared to free LmH. These molecular characteristics of LmH highlight its great potential for the pharmaceutical, biotechnological, and chemical industries. PMID- 25128100 TI - Comments on: "Quantitative evaluation of mechanical properties in tissue engineered auricular cartilage". PMID- 25128101 TI - A woman with warts, leg swelling, and deafness. AB - KEY TEACHING POINTS * We describe a 45-year-old woman with GATA2 deficiency associated with verrucae, lymphedema, immunodeficiency, and a history of infections and skin cancer. * GATA2 deficiency has variable clinical expressivity with differing presentations, including infection, hematopoietic abnormalities, immunodeficiency, lymphedema, and cancer. * Cutaneous manifestations include verruca vulgaris, soft tissue infections, lymphedema, and panniculitis. * Patients may have verrucae that can progress to squamous cell carcinomas; dermatologists therefore play an important role in managing these patients as members of a multidisciplinary team. PMID- 25128102 TI - Topical antimicrobial acne treatment tolerability: a meaningful factor in treatment adherence? PMID- 25128103 TI - The impact of obesity on the folliculosebaceous unit. PMID- 25128104 TI - Reply to 'what is the effect of obesity on the folliculosebaceous unit?'. PMID- 25128105 TI - Skin cancer, photoprotection, and skin of color. PMID- 25128106 TI - Reply to 'skin cancer, photoprotection, and skin of color'. PMID- 25128107 TI - Surgical margins for possibly malignant melanocytic lesions. PMID- 25128108 TI - Psoriasis or obesity is a risk factor for nonalcoholic fatty liver disease. PMID- 25128109 TI - Reply to 'surgical margins for possibly malignant melanocytic lesions'. PMID- 25128110 TI - Reply: surgical margins for possibly malignant melanocytic lesions and the overdiagnosis of melanoma. PMID- 25128111 TI - Complementary data for long-term infliximab use in psoriasis. PMID- 25128112 TI - Reply to 'complementary data for long-term infliximab use in psoriasis'. PMID- 25128113 TI - Filaggrin mutations as an archetype for understanding the pathophysiology of atopic dermatitis. PMID- 25128114 TI - Frontal fibrosing alopecia. PMID- 25128115 TI - Reply to 'frontal fibrosing alopecia'. PMID- 25128116 TI - Clinical efficacy of diphenylcyclopropenone in alopecia areata: retrospective data analysis of 50 patients. PMID- 25128117 TI - Early-onset mycosis fungoides among African American women: a single-institution study. PMID- 25128118 TI - Evaluation and diagnosis of the hair loss patient: part I. History and clinical examination. AB - Hair loss (alopecia) is a common problem and is often a major source of distress for patients. The differential diagnosis of alopecia includes both scarring and nonscarring alopecias. In addition, many hair shaft disorders can produce hair shaft fragility, resulting in different patterns of alopecia. Therefore, an organized and systematic approach is needed to accurately address patients' complaints to achieve the correct diagnosis. Part 1 of this 2-part continuing medical education article on alopecia describes history taking and the clinical examination of different hair loss disorders. It also provides an algorithmic diagnostic approach based on the most recent knowledge about different types of alopecia. PMID- 25128119 TI - Evaluation and diagnosis of the hair loss patient: part II. Trichoscopic and laboratory evaluations. AB - The use of trichoscopy for evaluating a number of hair and scalp disorders is gaining popularity. It is a simple and noninvasive in vivo tool for visualizing hair shafts and the scalp. Recently, alopecias have been classified according to their trichoscopic findings. The second part of this 2-part continuing medical education article reviews recent advances in this field and describes a systematic approach for using the differential diagnostic findings of trichoscopy in alopecia. PMID- 25128120 TI - Papular eruption associated with palifermin. PMID- 25128121 TI - A 52-year-old man with bullous pemphigoid and bullous cystitis. PMID- 25128122 TI - Successful topical adapalene treatment for the facial lesions of an adolescent case of epidermolytic ichthyosis. PMID- 25128125 TI - Trichoblastoma with dermoscopic features of a malignant tumor: three cases. PMID- 25128126 TI - Periungual Bowen disease mimicking chronic paronychia and diagnosed by dermoscopy. PMID- 25128127 TI - Optimizing the efficacy of targeted phototherapy by marking early vitiligo lesions after visualizing under a Wood's lamp. PMID- 25128128 TI - Use of the Unna sleeve for severe, treatment-resistant idiopathic pruritus. PMID- 25128129 TI - Extraosseous extension of multiple myeloma: a cutaneous herald to systemic disease. PMID- 25128130 TI - Solar urticaria to visible light triggered by light-emitting diode therapy. PMID- 25128131 TI - Cheilitis and urticaria associated with stannous fluoride in toothpaste. PMID- 25128132 TI - Distinctive cutaneous findings due to a rare complication from a warming device. PMID- 25128133 TI - Reactive hemophagocytic syndrome in a patient with adult-onset Still disease. PMID- 25128134 TI - Umbilical endometriosis elucidates cause of recurrent pneumothorax. PMID- 25128135 TI - Generalized granuloma annulare after varicella infection: Wolf isotopic response? PMID- 25128136 TI - Photo-induced Stevens-Johnson syndrome. PMID- 25128137 TI - Pili multigemini/trichofolliculoma-like organoid nevus. PMID- 25128138 TI - Subcorneal pustular dermatosis associated with Mycoplasma pneumoniae infection. PMID- 25128139 TI - Rapid deterioration in a patient with primary aggressive cutaneous epidermotropic CD8+ cytotoxic T-cell ('Berti') lymphoma after administration of adalimumab. PMID- 25128140 TI - Rickettsia parkeri: eschar diagnosis. PMID- 25128141 TI - A rapidly progressive and fatal case of atypical acute generalized exanthematous pustulosis. PMID- 25128142 TI - Peripheral facial palsy after topical photodynamic therapy for facial actinic keratoses. PMID- 25128143 TI - Demodicidosis on the arms of a patient with pemphigus foliaceus. PMID- 25128144 TI - Primary cutaneous nocardiosis in an immunocompetent host following laser resurfacing. PMID- 25128145 TI - Giant cellulitis-like Sweet syndrome in the setting of autoimmune disease. PMID- 25128146 TI - Cutaneous polyarteritis nodosa presenting as a solitary blue toe. PMID- 25128147 TI - Major response to vemurafenib in patient with severe cutaneous Langerhans cell histiocytosis harboring BRAF V600E mutation. PMID- 25128148 TI - Extensive scleredema adultorum with loss of eccrine glands. PMID- 25128149 TI - Downregulation of microRNA-498 in colorectal cancers and its cellular effects. AB - miR-498 is a non-coding RNA located intergenically in 19q13.41. Due to its predicted targeting of several genes involved in control of cellular growth, we examined the expression of miR-498 in colon cancer cell lines and a large cohort of patients with colorectal adenocarcinoma. Two colon cancer cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. The expression of miR-498 was tested in these cell lines by using quantitative real-time polymerase chain reaction (qRT-PCR). Tissues from 80 patients with surgical resection of colorectum (60 adenocarcinomas and 20 non neoplastic tissues) were tested for miR-498 expression by qRT-PCR. In addition, an exogenous miR-498 (mimic) was used to detect the miRNA's effects on cell proliferation and cell cycle events in SW480 using MTT calorimetric assay and flow cytometry respectively. The colon cancer cell lines showed reduced expression of miR-498 compared to a normal colonic epithelial cell line. Mimic driven over expression of miR-498 in the SW480 cell line resulted in reduced cell proliferation and increased proportions of G2-M phase cells. In tissues, miR-498 expression was too low to be detected in all colorectal adenocarcinoma compared to non-neoplastic tissues. This suggests that the down regulation of miR-498 in colorectal cancer tissues and the direct suppressive cellular effect noted in cancer cell lines implies that miR-498 has some direct or indirect role in the pathogenesis of colorectal adenocarcinomas. PMID- 25128151 TI - Effect of cholesterol and ergosterol on the antibiotic amphotericin B interactions with dipalmitoylphosphatidylcholine monolayers: X-ray reflectivity study. AB - Amphotericin B is a Streptomyces nodosus metabolite and one of the oldest polyene antibiotics used in the treatment of invasive systemic fungal infections. Despite its over 50-year existence in clinical practice and the recognition of amphotericin B as the gold standard in the treatment of serious systemic mycosis, it still remains one of the most toxic pharmaceuticals. Understanding of the processes at the molecular levels and the interactions between amphotericin B with lipid membranes containing sterols should elucidate the mechanisms of the action and toxicity of this widely used antibiotic. In this work, we use X-ray reflectivity to study the structural changes on a molecular scale after amphotericin B incorporation. These changes are accompanied by an increase in monolayer surface pressure which is more pronounced for ergosterol - rather than cholesterol-rich membranes. The data indicate that this difference is not due to the higher affinity of amphotericin B towards ergosterol-containing membranes but is rather due to a ~3Angstrom corrugation of the monolayer. Furthermore, the total quantity of amphotericin B incorporated into lipid monolayers containing cholesterol and ergosterol is the same. PMID- 25128152 TI - Characterization of 3-methoxy flavones for their interaction with ABCG2 as suggested by ATPase activity. AB - Breast Cancer Resistance Protein (BCRP/ABCG2) belongs to the superfamily of ATP binding cassette (ABC) transporters. Characteristic of some of these transporter proteins is the transport of a variety of structurally unrelated substances against a concentration gradient by using the energy of ATP hydrolysis. ABCG2 has been found to confer multidrug resistance (MDR) in cancer cells. Several anticancer drugs have been identified as ABCG2 substrates including mitoxantrone, etoposide and topotecan. As inhibition of the transporter is one of the strategies to overcome MDR, we have synthesized and tested several 3-methoxy flavones and investigated them for their ABCG2 inhibition. Among these, pentamethyl quercetin (compound 4) and pentamethyl morin (compound 5) were found to be fluorescent and hence screened for their possible transport by ABCG2 using confocal microscopy. This study showed that pentamethyl quercetin was far less accumulated in ABCG2 overexpressing MDCK BCRP cells as compared to MDCK sensitive cells, suggesting possible efflux of this compound by ABCG2. Pentamethyl morin showed no visible difference in both cell lines. Based on this observation, we studied several other fluorescent 3-methoxy flavones for their accumulation in ABCG2 overexpressing cells. To confirm the substrate or inhibitor nature of the tested compounds, these compounds were further investigated by ATPase assay. If stimulation of the transporter ATPase activity is detected, one can conclude that the compound is probably a transported substrate. All compounds except pentamethyl morin (compound 5) and tetramethyl quercetin (compound 6) were found to stimulate ATPase activity pointing to possible substrates despite being potent inhibitors of ABCG2. PMID- 25128153 TI - Labeling phospholipid membranes with lipid mimetic luminescent metal complexes. AB - Lipid-mimetic metallosurfactant based luminophores are promising candidates for labeling phospholipid membranes without altering their biophysical characteristics. The metallosurfactants studied exhibit high structural and physicochemical similarity to phospholipid molecules, designed to incorporate into the membrane structure without the need for covalent attachment to a lipid molecule. In this work, two lipid-mimetic phosphorescent metal complexes are described: [Ru(bpy)2(dn-bpy)](2+) and [Ir(ppy)2(dn-bpy)](+) where bpy is 2,2' bipyridine, dn-bpy is 4,4'-dinonyl-2,2'-bipyridine and ppy is 2-phenylpyridine. Apart from being lipid-mimetic in size, shape and physical properties, both complexes exhibit intense photoluminescence and enhanced photostability compared with conventional organic fluorophores, allowing for prolonged observation. Moreover, the large Stokes shift and long luminescence lifetime associated with these complexes make them more suitable for spectroscopic studies. The complexes are easily incorporated into dimyristoil-phosphatidyl-choline (DMPC) liposomes by mixing in the organic solvent phase. DLS reveals the labeled membranes form liposomes of similar size to that of neat DMPC membrane. Synchrotron Small-Angle X-ray Scattering (SAXS) measurements confirmed that up to 5% of either complex could be incorporated into DMPC membranes without producing any structural changes in the membrane. Fluorescence microscopy reveals that 0.5% label content is sufficient for imaging. Atomic Force Microscopic imaging confirms that liposomes of the labeled bilayers on a mica surface can fuse into a flat lamellar membrane that is morphologically identical to neat lipid membranes. These results demonstrate the potential of such lipid-mimetic luminescent metal complexes as a new class of labels for imaging lipid membranes. PMID- 25128150 TI - A syndecan-4 binding peptide derived from laminin 5 uses a novel PKCepsilon pathway to induce cross-linked actin network (CLAN) formation in human trabecular meshwork (HTM) cells. AB - In this study, we examined the role(s) of syndecan-4 in regulating the formation of an actin geodesic dome structure called a cross-linked actin network (CLAN) in which syndecan-4 has previously been localized. CLANs have been described in several different cell types, but they have been most widely studied in human trabecular meshwork (HTM) cells where they may play a key role in controlling intraocular pressure by regulating aqueous humor outflow from the eye. In this study we show that a loss of cell surface synedcan-4 significantly reduces CLAN formation in HTM cells. Analysis of HTM cultures treated with or without dexamethasone shows that laminin 5 deposition within the extracellular matrix is increased by glucocorticoid treatment and that a laminin 5-derived, syndecan-4 binding peptide (PEP75), induces CLAN formation in TM cells. This PEP75-induced CLAN formation was inhibited by heparin and the broad spectrum PKC inhibitor Ro 31-7549. In contrast, the more specific PKCalpha inhibitor Go 6976 had no effect, thus excluding PKCalpha as a downstream effector of syndecan-4 signaling. Analysis of PKC isozyme expression showed that HTM cells also expressed both PKCgamma and PKCepsilon. Cells treated with a PKCepsilon agonist formed CLANs while a PKCalpha/gamma agonist had no effect. These data suggest that syndecan-4 is essential for CLAN formation in HTM cells and that a novel PKCepsilon-mediated signaling pathway can regulate formation of this unique actin structure. PMID- 25128154 TI - Structural dynamics of the cell wall precursor lipid II in the presence and absence of the lantibiotic nisin. AB - Representing a physiological "Achilles' heel", the cell wall precursor lipid II (LII) is a prime target for various classes of antibiotics. Over the years LII binding agents have been recognized as promising candidates and templates in the search for new antibacterial compounds to complement or replace existing drugs. To elucidate the molecular structural basis underlying LII functional mechanism and to better understand if and how lantibiotic binding alters the molecular behavior of LII, we performed molecular dynamics (MD) simulations of phospholipid membrane-embedded LII in the absence and presence of the LII-binding lantibiotic nisin. In a series of 2*4 independent, unbiased 100ns MD simulations we sampled the conformational dynamics of nine LII as well as nine LII-nisin complexes embedded in an aqueous 150mM NaCl/POPC phospholipid membrane environment. We found that nisin binding to LII induces a reduction of LII mobility and flexibility, an outward shift of the LII pentapeptide, an inward movement of the LII disaccharide section, and an overall deeper insertion of the LII tail group into the membrane. The latter effect might indicate an initial step in adopting a stabilizing, scaffold-like structure in the process of nisin-induced membrane leakage. At the same time nisin conformation and LII interaction remain similar to the 1WCO LII-nisin NMR solution structure. PMID- 25128155 TI - Towards the importance of minimum toe clearance in level ground walking in a healthy elderly population. AB - Tripping is presumed to be the principal cause for falls during walking. At minimum toe clearance, the potential for trip-related falls is considered to be highest. Thus, controlling minimum toe clearance is essential for walking without tripping. In theory, the central nervous system should therefore give priority to accurate control of the variability in minimum toe clearance, as compared to other gait parameters, since people tend to only modify variability in any given task if it interferes with the task performance. The aim of this study was to determine whether elderly individuals show less increase in variability of minimum toe clearance during a dual-task condition (where an increase of gait variability is provoked), while allowing a larger range of variability in the other gait parameters. Forty elderly participants walked back and forth on a 25 m long track for five minutes. They then walked a second time performing an additional cognitive task. The variability in stride time, stride length and minimum toe clearance as well as dual-task costs of each gait parameter were calculated for each walk. The variability in minimum toe clearance did not change during dual task-walking, whereas the variability of stride length and stride time increased, showing dual-task costs of about 66% and 84%, respectively. To avoid additional detrimental load on the central nervous system, the modification of task-irrelevant variability may be tolerated during dual-task conditions, whereas minimum toe clearance is controlled with high priority. PMID- 25128156 TI - Clinimetric properties of the Tinetti Mobility Test, Four Square Step Test, Activities-specific Balance Confidence Scale, and spatiotemporal gait measures in individuals with Huntington's disease. AB - BACKGROUND AND PURPOSE: Individuals with Huntington's disease (HD) experience balance and gait problems that lead to falls. Clinicians currently have very little information about the reliability and validity of outcome measures to determine the efficacy of interventions that aim to reduce balance and gait impairments in HD. This study examined the reliability and concurrent validity of spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step Test (FSST), and Activities-specific Balance Confidence (ABC) Scale in individuals with HD. METHODS: Participants with HD [n = 20; mean age +/- SD=50.9 +/- 13.7; 7 male] were tested on spatiotemporal gait measures and the TMT, FSST, and ABC Scale before and after a six week period to determine test-retest reliability and minimal detectable change (MDC) values. Linear relationships between gait and clinical measures were estimated using Pearson's correlation coefficients. RESULTS: Spatiotemporal gait measures, the TMT total and the FSST showed good to excellent test-retest reliability (ICC > 0.75). MDC values were 0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively, four points for the TMT, and 3s for the FSST. The TMT and FSST were highly correlated with most spatiotemporal measures. The ABC Scale demonstrated lower reliability and less concurrent validity than other measures. CONCLUSIONS: The high test-retest reliability over a six week period and concurrent validity between the TMT, FSST, and spatiotemporal gait measures suggest that the TMT and FSST may be useful outcome measures for future intervention studies in ambulatory individuals with HD. PMID- 25128157 TI - An anti-apoptotic B-cell lymphoma-2 (BCL-2) from Channa striatus: Sequence analysis and delayed and advanced gene expression in response to fungal, bacterial and poly I:C induction. AB - B-cell lymphoma-2 (BCL-2) is a suppressor of apoptosis and inhibits the caspase dependent apoptosis pathway. In this study, we report molecular characterization of a cDNA sequence encoded of BCL-2 from striped murrel, Channa striatus. A partial cDNA sequence of CsBCL-2 was identified from the striped murrel cDNA library during annotation. Subsequently, the full length CsBCL-2 cDNA sequence was obtained by an internal sequencing method using a forward primer. The sequence contains 699 nucleotide base pairs which encode 232 amino acid residues. The domain and motif analysis revealed that the CsBCL-2 polypeptide consists of BCL-2 homologous domain BH4 at the N-terminal region between 4 and 21 and the BCL 2 homologous domains BH1, BH2 and BH3 between 87 and 187. The CsBCL-2 polypeptide sequence does not have a signal peptide region, but it consists of two novel transmembrane regions at 134-152 and 209-226. The sequence analysis showed that the CsBCL-2 has highest sequence identity (70%) with BCL-2 like protein 1 (BCL-2 L1) from pufferfish Takifugu rubripes. The phylogenetic analysis showed that the CsBCL-2 was situated in the BCL-2 L1 fish clade. The secondary analysis showed that the CsBCL-2 protein consists of 132 amino acid residues in the alpha-helical region and 100 amino acid residues in the random coil region. The validated 3D structure of CsBCL-2 showed the active residues Gly(135) and Arg(136) in the 7th alpha-helical position, whereas Trp(178) is in the 9th alpha-helical region. CsBCL-2 mRNA transcription is predominately present in spleen and is upregulated upon being induced with fungus Aphanomyces invadans, bacteria Aeromonas hydrophila, Escherichia coli LPS, Laminaria digitata beta-1,3-glucan and poly I:C. Overall, the CsBCL-2 mRNA transcription results indicate the potential involvement of CsBCL-2 in immune system of C. striatus. However, further research at proteomic level is necessary to examine these predictions. PMID- 25128158 TI - Porcine NOD1 polymorphisms with impaired ligand recognition and their distribution in pig populations. AB - Nucleotide-binding oligomerization domain 1 (NOD1) is a cytosolic pattern recognition receptor that recognizes gamma-d-glutamyl-meso-diaminopimelic acid (iE-DAP), a component of bacterial peptidoglycan. NOD1 is thought to be involved in the immune homeostasis mediated by intestinal microbiota as well as the host defense against infection. In this study, we identified 12 synonymous and nine nonsynonymous single nucleotide polymorphisms (SNPs) in the coding sequence of porcine NOD1 within major commercial breeds in the swine industry. Among the nonsynonymous SNPs, two amino-acid alterations located in the leucine-rich repeats region, glycine to glutamic acid at position 641 (G641E) and aspartic acid to asparagine at position 918 (D918N), impaired iE-DAP-induced activation of nuclear factor-kappaB. These alleles showed the recessive mode of inheritance and therefore are likely to be maintained in pig populations at high frequencies. These results suggest the possibility for improvement in disease resistance by eliminating the G641E and D918N alleles of NOD1 from commercial pig populations. PMID- 25128159 TI - Reply: To PMID 24529621. PMID- 25128160 TI - Pulsatile airway obstruction found on ventilator pulmonary graphics. PMID- 25128161 TI - Constipation: a Brown Herring. PMID- 25128162 TI - Intimate partner violence increases adverse outcomes at birth and in early infancy. AB - OBJECTIVE: To determine the effect of intimate partner violence (IPV) on birth outcomes and infant hospitalization. STUDY DESIGN: Hospitalization records for the first 4 months of life for infants born in the Military Health System in 2006 2007 were linked to Family Advocacy Program-substantiated cases of IPV among military parents. Adverse outcomes were identified using International Classification of Diseases, Ninth Revision codes. Logistic regression modeling calculated the OR of children exposed to IPV experiencing adverse outcomes. RESULTS: A total of 204,546 infants were born during the study period. Among these, 173,026 infants (85%) were linked to active duty military parents. 31,603 infants (18%) experienced adverse outcomes, and 3059 infants (1.8%) were born into families with IPV. The infants exposed to IPV had a 31% increased odds of experiencing adverse outcomes compared with infants without known IPV exposure. IPV exposure increased the odds of the following outcomes: prematurity (OR, 1.45; 95% CI, 1.29-1.62), low birth weight (OR, 1.57; 95% CI, 1.25-1.97), respiratory problems (OR, 1.17; 95% CI, 1.04-1.32), neonatal hospitalization (OR, 1.39; 95% CI, 1.20-1.61), and postneonatal hospitalization (OR, 1.52; 95% CI, 1.29-1.81). After controlling for prematurity and demographic variables, IPV exposure was associated with low birth weight (OR, 1.52; 95% CI, 1.16-1.99), neonatal hospitalization (OR, 1.24; 95% CI, 1.02-1.49), and postneonatal hospitalization (OR, 1.27; 95% CI, 1.03-1.56). CONCLUSION: Infants exposed to IPV are more likely to experience adverse birth outcomes and infant hospitalization. Routinely addressing IPV during prenatal and early pediatric visits may potentially prevent these adverse outcomes. PMID- 25128163 TI - Mapping human resources for eye health in 21 countries of sub-Saharan Africa: current progress towards VISION 2020. AB - BACKGROUND: Development of human resources for eye health (HReH) is a major focus of the Global Action Plan 2014 to 2019 to reduce the prevalence of avoidable visual impairment by 25% by the year 2019. The eye health workforce is thought to be much smaller in sub-Saharan Africa than in other regions of the world but data to support this for policy-making is scarce. We collected HReH and cataract surgeries data from 21 countries in sub-Sahara to estimate progress towards key suggested population-based VISION 2020 HReH indicators and cataract surgery rates (CSR) in 2011. METHODS: Routinely collected data on practitioner and surgery numbers in 2011 was requested from national eye care coordinators via electronic questionnaires. Telephone and e-mail discussions were used to determine data collection strategies that fit the national context and to verify reported data quality. Information was collected on six practitioner cadres: ophthalmologists, cataract surgeons, ophthalmic clinical officers, ophthalmic nurses, optometrists and 'mid-level refractionists' and combined with publicly available population data to calculate practitioner to population ratios and CSRs. Associations with development characteristics were conducted using Wilcoxon rank sum tests and Spearman rank correlations. RESULTS: HReH data was not easily available. A minority of countries had achieved the suggested VISION 2020 targets in 2011; five countries for ophthalmologists/cataract surgeons, four for ophthalmic nurses/clinical officers and two for CSR. All countries were below target for optometrists, even when other cadres who perform refractions as a primary duty were considered. The regional (sample) ratio for surgeons (ophthalmologists and cataract surgeons) was 2.9 per million population, 5.5 for ophthalmic clinical officers and nurses, 3.7 for optometrists and other refractionists, and 515 for CSR. A positive correlation between GDP and CSR as well as many practitioner ratios was observed (CSR P = 0.0042, ophthalmologists P = 0.0034, cataract surgeons, ophthalmic nurses and optometrists 0.1 > P > 0.05). CONCLUSIONS: With only a minority of countries in our sample having reached suggested ophthalmic cadre targets and none having reached targets for refractionists in 2011, substantially more targeted investment in HReH may be needed for VISION 2020 aims to be achieved in sub-Saharan Africa. PMID- 25128164 TI - Aldosterone augments Na+-induced reduction of cardiac norepinephrine reuptake. AB - Impairment of the cardiac norepinephrine (NE) reuptake by the neuronal NE transporter contributes to enhanced cardiac NE net release in congestive heart failure. Elevated plasma levels of aldosterone (AL) promote sympathetic overstimulation in failing hearts by unclear mechanisms. Our aim was to evaluate if elevated AL and/or alterations in Na(+) intake regulate cardiac NE reuptake. To test the effects of AL and Na(+) on cardiac NE reuptake, Wistar rats were fed a normal-salt (NS) diet (0.2% NaCl), a low-salt (LS) diet (0.015% NaCl), or a high-salt (HS) diet (8% NaCl). Another group of animals received AL infusion alone (0.75 MUg/h) or AL infusion plus HS diet. Specific cardiac [(3)H]NE uptake via the NE transporter in a Langendorff preparation and AL plasma levels were measured at different time points between 5 and 42 days of treatment. To compare these findings from healthy animals with a disease model, Dahl salt-sensitive rats were investigated as a model of congestive heart failure with endogenously elevated AL. In summary, neither exogenous nor endogenous elevations of AL alone were sufficient to reduce cardiac NE reuptake. Only the HS diet induced a reduction of NE reuptake by 26%; additional infusion of AL augmented this effect to a further reduction of NE reuptake by 36%. In concordance, Dahl salt-sensitive rats treated with a HS diet displayed elevated AL and a marked reduction of NE reuptake. We conclude that exogenous or endogenous AL elevations alone do not reduce cardiac NE reuptake, but AL serves as an additional factor that negatively regulates cardiac NE reuptake in concert with HS intake. PMID- 25128165 TI - Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application. AB - Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a 1 liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 +/ 22%) occurred at 2.4 s; and steady-state decrease (-15 +/- 5%), at 6 s. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 +/- 3.9 to 6.7 +/- 2.8/min (P < 0.0001) with a concomitant increase in tidal volume from 499 +/- 206 to 1,177 +/- 497 ml (P < 0.001). Consequently, steady-state MSNA was decreased by 31% (P < 0.005). In patients without respiratory modulation, there were no significant changes in respiratory frequency, tidal volume, and steady-state MSNA. Thus slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure. PMID- 25128166 TI - AMPK activation by glucagon-like peptide-1 prevents NADPH oxidase activation induced by hyperglycemia in adult cardiomyocytes. AB - Exposure of cardiomyocytes to high glucose concentrations (HG) stimulates reactive oxygen species (ROS) production by NADPH oxidase (NOX2). NOX2 activation is triggered by enhanced glucose transport through a sodium-glucose cotransporter (SGLT) but not by a stimulation of glucose metabolism. The aim of this work was to identify potential therapeutic approaches to counteract this glucotoxicity. In cultured adult rat cardiomyocytes incubated with 21 mM glucose (HG), AMP activated protein kinase (AMPK) activation by A769662 or phenformin nearly suppressed ROS production. Interestingly, glucagon-like peptide 1 (GLP-1), a new antidiabetic drug, concomitantly induced AMPK activation and prevented the HG mediated ROS production (maximal effect at 100 nM). alpha2-AMPK, the major isoform expressed in cardiomyocytes (but not alpha1-AMPK), was activated in response to GLP-1. Anti-ROS properties of AMPK activators were not related to changes in glucose uptake or glycolysis. Using in situ proximity ligation assay, we demonstrated that AMPK activation prevented the HG-induced p47phox translocation to caveolae, whatever the AMPK activators used. NOX2 activation by either alpha-methyl-d-glucopyranoside, a glucose analog transported through SGLT, or angiotensin II was also counteracted by GLP-1. The crucial role of AMPK in limiting HG-mediated NOX2 activation was demonstrated by overexpressing a constitutively active form of alpha2-AMPK using adenoviral infection. This overexpression prevented NOX2 activation in response to HG, whereas GLP-1 lost its protective action in alpha2-AMPK-deficient mouse cardiomyocytes. Under HG, the GLP-1/AMPK pathway inhibited PKC-beta2 phosphorylation, a key element mediating p47phox translocation. In conclusion, GLP-1 induces alpha2-AMPK activation and blocks HG-induced p47phox translocation to the plasma membrane, thereby preventing glucotoxicity. PMID- 25128167 TI - Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function. AB - Regulatory T cells (Tregs) play a pivotal role in suppressing immune responses regulating behavior and gene expression in effector T cells, macrophages, and dendritic cells. Tregs infiltrate the infarcted myocardium; however, their role the inflammatory and reparative response after myocardial infarction remains poorly understood. We used FoxP3(EGFP) reporter mice to study Treg trafficking in the infarcted heart and examined the effects of Treg depletion on postinfarction remodeling using an anti-CD25 antibody. Moreover, we investigated the in vitro effects of Tregs on cardiac fibroblast phenotype and function. Low numbers of Tregs infiltrated the infarcted myocardium after 24-72 h of reperfusion. Treg depletion had no significant effects on cardiac dysfunction and scar size after reperfused myocardial infarction but accelerated ventricular dilation and accentuated apical remodeling. Enhanced myocardial dilation in Treg-depleted animals was associated with increased expression of chemokine (C-C motif) ligand 2 and accentuated macrophage infiltration. In vitro, Tregs modulated the cardiac fibroblast phenotype, reducing expression of alpha-smooth muscle actin, decreasing expression of matrix metalloproteinase-3, and attenuating contraction of fibroblast-populated collagen pads. Our findings suggest that endogenous Tregs have modest effects on the inflammatory and reparative response after myocardial infarction. However, the anti-inflammatory and matrix-preserving properties of Tregs may suggest a role for Treg-based cell therapy in the attenuation of adverse postinfarction remodeling. PMID- 25128168 TI - Aging impairs smooth muscle-mediated regulation of aortic stiffness: a defect in shock absorption function? AB - Increased aortic stiffness is an early and independent biomarker of cardiovascular disease. Here we tested the hypothesis that vascular smooth muscle cells (VSMCs) contribute significantly to aortic stiffness and investigated the mechanisms involved. The relative contributions of VSMCs, focal adhesions (FAs), and matrix to stiffness in mouse aorta preparations at optimal length and with confirmed VSMC viability were separated by the use of small-molecule inhibitors and activators. Using biomechanical methods designed for minimal perturbation of cellular function, we directly quantified changes with aging in aortic material stiffness. An alpha adrenoceptor agonist, in the presence of N(G)-nitro-l arginine methyl ester (l-NAME) to remove interference of endothelial nitric oxide, increases stiffness by 90-200% from baseline in both young and old mice. Interestingly, increases are robustly suppressed by the Src kinase inhibitor PP2 in young but not old mice. Phosphotyrosine screening revealed, with aging, a biochemical signature of markedly impaired agonist-induced FA remodeling previously associated with Src signaling. Protein expression measurement confirmed a decrease in Src expression with aging. Thus we report here an additive model for the in vitro biomechanical components of the mouse aortic wall in which 1) VSMCs are a surprisingly large component of aortic stiffness at physiological lengths and 2) regulation of the VSMC component through FA signaling and hence plasticity is impaired with aging, diminishing the aorta's normal shock absorption function in response to stressors. PMID- 25128169 TI - Prolonged uterine artery nitric oxide synthase inhibition modestly alters basal uteroplacental vasodilation in the last third of ovine pregnancy. AB - Mechanisms regulating uteroplacental blood flow (UPBF) in pregnancy remain unclear, but they likely involve several integrated signaling systems. Endothelium-derived nitric oxide (NO) is considered an important contributor, but the extent of its involvement is unclear. Bolus intra-arterial infusions of nitro l-arginine methyl ester (l-NAME) modestly decrease ovine basal UPBF; however, the doses and duration of infusion may have been insufficient. We, therefore, examined prolonged uterine artery (UA) NO synthase inhibition with l-NAME throughout the last third of ovine pregnancy by performing either continuous 30 min UA infusion dose responses (n = 4) or 72-h UA infusions (0.01 mg/ml) at 104 108, 118-125, and 131-137 days of gestation (n = 7) while monitoring mean arterial pressure (MAP), heart rate (HR), and UPBF. Uteroplacental vascular resistance (UPVR) was calculated, and uterine cGMP synthesis was measured. Thirty minute UA l-NAME infusions did not dose dependently decrease UPBF, increase UPVR, or decrease uterine cGMP synthesis (P > 0.1); however, MAP rose and HR fell modestly. Prolonged continuous 72-h UA l-NAME infusions decreased UPBF ~32%, increased UPVR ~68% (P <= 0.001), and decreased uterine cGMP synthesis 70% at 54 72 h (P <= 0.004); the noninfused uterine horn was unaffected. These findings were associated with ~10% increases in MAP and decreases in HR that were greater at 104-108 than 118-125 and 131-137 days of gestation (P = 0.006). Although uterine and UA NO and cGMP synthesis increase severalfold during ovine pregnancy, they contribute modestly to the maintenance and rise in UPBF in the last third of gestation. Thus, local UA NO may primarily modulate vasoconstrictor responses. Notably, the systemic vasculature appears more sensitive than the uterine vasculature to NO synthase inhibition. PMID- 25128170 TI - Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men. AB - In animal studies, the polyphenol resveratrol has been shown to influence several pathways of importance for angiogenesis in skeletal muscle. The aim of the present study was to examine the angiogenic effect of resveratrol supplementation with parallel exercise training in aged men. Forty-three healthy physically inactive aged men (65 +/- 1 yr) were divided into 1) a training group that conducted 8 wk of intense exercise training where half of the subjects received a daily intake of either 250 mg trans-resveratrol (n = 14) and the other half received placebo (n = 13) and 2) a nontraining group that received either 250 mg trans-resveratrol (n = 9) or placebo (n = 7). The group that trained with placebo showed a ~20% increase in the capillary-to-fiber ratio, an increase in muscle protein expression of VEGF, VEGF receptor-2, and tissue inhibitor of matrix metalloproteinase (TIMP-1) but unaltered thrombospodin-1 levels. Muscle interstitial VEGF and thrombospodin-1 protein levels were unchanged after the training period. The group that trained with resveratrol supplementation did not show an increase in the capillary-to-fiber ratio or an increase in muscle VEGF protein. Muscle TIMP-1 protein levels were lower in the training and resveratrol group than in the training and placebo group. Both training groups showed an increase in forkhead box O1 protein. In nontraining groups, TIMP-1 protein was lower in the resveratrol-treated group than the placebo-treated group after 8 wk. In conclusion, these data show that exercise training has a strong angiogenic effect, whereas resveratrol supplementation may limit basal and training-induced angiogenesis. PMID- 25128172 TI - Hyperbilirubinemia modulates myocardial function, aortic ejection, and ischemic stress resistance in the Gunn rat. AB - Mildly elevated circulating unconjugated bilirubin (UCB) is associated with protection against hypertension and ischemic heart disease. We assessed whether endogenously elevated bilirubin in Gunn rats modifies cardiovascular function and resistance to ischemic insult. Hearts were assessed ex vivo (Langendorff perfusion) and in vivo (Millar catheterization and echocardiography), and left ventricular myocardial gene expression was measured via quantitative real-time PCR. Ex vivo analysis revealed reduced intrinsic contractility in the Gunn myocardium (+dP/dt: 1,976 +/- 622 vs. 2,907 +/- 334 mmHg/s, P < 0.01; -dP/dt: 1,435 +/- 372 vs. -2,234 +/- 478 mmHg/s, P < 0.01), which correlated positively with myocardial UCB concentration (P < 0.05). In vivo analyses showed no changes in left ventricular contractile parameters and ejection (fractional shortening and ejection fraction). However, Gunn rats exhibited reductions in the rate of aortic pressure development (3,008 +/- 461 vs. 4,452 +/- 644 mmHg/s, P < 0.02), mean aortic velocity (439 +/- 64 vs. 644 +/- 62 mm/s, P < 0.01), and aortic volume time integral pressure gradient (2.32 +/- 0.65 vs. 5.72 +/- 0.74 mmHg, P < 0.01), in association with significant aortic dilatation (12-24% increase in aortic diameter, P < 0.05). Ex vivo Gunn hearts exhibited improved ventricular function after 35 min of ischemia and 90 min of reperfusion (63 +/- 14 vs. 35 +/- 12%, P < 0.01). These effects were accompanied by increased glutathione peroxidase and reduced superoxide dismutase and phospholamban gene expression in Gunn rat myocardium (P < 0.05). These data collectively indicate that hyperbilirubinemia in Gunn rats 1) reduces intrinsic cardiac contractility, which is compensated for in vivo; 2) induces aortic dilatation, which may beneficially influence aortic ejection velocities and pressures; and 3) may improve myocardial stress resistance in association with beneficial transcriptional changes. These effects may contribute to protection from cardiovascular disease with elevated bilirubin. PMID- 25128171 TI - Myofilament dysfunction contributes to impaired myocardial contraction in the infarct border zone. AB - After myocardial infarction, a poorly contracting nonischemic border zone forms adjacent to the infarct. The cause of border zone dysfunction is unclear. The goal of this study was to determine the myofilament mechanisms involved in postinfarction border zone dysfunction. Two weeks after anteroapical infarction of sheep hearts, we studied in vitro isometric and isotonic contractions of demembranated myocardium from the infarct border zone and a zone remote from the infarct. Maximal force development (Fmax) of the border zone myocardium was reduced by 31 +/- 2% versus the remote zone myocardium (n = 6/group, P < 0.0001). Decreased border zone Fmax was not due to a reduced content of contractile material, as assessed histologically, and from myosin content. Furthermore, decreased border zone Fmax did not involve altered cross-bridge kinetics, as assessed by muscle shortening velocity and force development kinetics. Decreased border zone Fmax was associated with decreased cross-bridge formation, as assessed from muscle stiffness in the absence of ATP where cross-bridge formation should be maximized (rigor stiffness was reduced 34 +/- 6%, n = 5, P = 0.011 vs. the remote zone). Furthermore, the border zone myocardium had significantly reduced phosphorylation of myosin essential light chain (ELC; 41 +/- 10%, n = 4, P < 0.05). However, for animals treated with doxycycline, an inhibitor of matrix metalloproteinases, rigor stiffness and ELC phosphorylation were not reduced in the border zone myocardium, suggesting that doxycycline had a protective effect. In conclusion, myofilament dysfunction contributes to postinfarction border zone dysfunction, myofilament dysfunction involves impaired cross-bridge formation and decreased ELC phosphorylation, and matrix metalloproteinase inhibition may be beneficial for limiting postinfarct border zone dysfunction. PMID- 25128173 TI - Type 2 diabetes: increased expression and contribution of IKCa channels to vasodilation in small mesenteric arteries of ZDF rats. AB - Impaired endothelial function, which is dysregulated in diabetes, also precedes hypertension. We hypothesized that in Type 2 diabetes, the impaired endothelium dependent relaxation is due to a loss of endothelium-derived hyperpolarization (EDH) that is regulated by impaired ion channel function. Zucker diabetic fatty (ZDF), Zucker heterozygote, and homozygote lean control rats were used as the experimental models in our study. Third-order mesenteric arteries were dissected and mounted on a pressure myograph; mRNA was quantified by RT-PCR and channel proteins by Western blotting. Under nitric oxide (NO) synthase and cyclooxygenase inhibition, endothelial stimulation with ACh fully relaxes control but not diabetic arteries. In contrast, when small-conductance calcium-activated potassium (KCa) channels and intermediate- and large-conductance KCa (I/BKCa) are inhibited with apamin and charybdotoxin, NO is able to compensate for ACh-induced relaxation in control but not in diabetic vessels. After replacement of charybdotoxin with 1-[(2-chlorophenyl)diphenylmethyl]-(1)H-pyrazole (TRAM-34; IKCa inhibitor), ACh-induced relaxation in diabetic animals is attenuated. Specific inhibition with TRAM-34 or charybdotoxin attenuates ACh relaxation in diabetes. Stimulation with 1-ethyl-2-benzimidazolinone (IKCa activator) shows a reduced relaxation in diabetes. Activation of BKCa with 1,3-dihydro-1-[2-hydroxy 5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-(2)H-benzimidazol-2-one NS619 leads to similar relaxations of control and diabetic arteries. RT-PCR and Western blot analysis demonstrate elevated mRNA and protein expression levels of IKCa in diabetes. Our results suggest that the compensatory effect of NO and EDH associated, endothelium-dependent relaxation is reduced in ZDF rats. Specific blockade of IKCa with TRAM-34 reduces NO and EDH-type relaxation in diabetic rats, indicating an elevated contribution of IKCa in diabetic small mesenteric artery relaxation. This finding correlates with increased IKCa mRNA and protein expression in this vessel. PMID- 25128174 TI - Unexpected maturation of PI3K and MAPK-ERK signaling in fetal ovine cardiomyocytes. AB - In the first two-thirds of gestation, ovine fetal cardiomyocytes undergo mitosis to increase cardiac mass and accommodate fetal growth. Thereafter, some myocytes continue to proliferate while others mature and terminally differentiate into binucleated cells. At term (145 days gestational age; dGA) about 60% of cardiomyocytes become binucleated and exit the cell cycle under hormonal control. Rising thyroid hormone (T3) levels near term (135 dGA) inhibit proliferation and stimulate maturation. However, the degree to which intracellular signaling patterns change with age in response to T3 is unknown. We hypothesized that in vitro activation of ERK, Akt, and p70(S6K) by two regulators of cardiomyocyte cell cycle activity, T3 and insulin like growth factor-1 (IGF-1), would be similar in cardiomyocytes at gestational ages 100 and 135 dGA. IGF-1 and T3 each independently stimulated phosphorylation of ERK, Akt, and p70(S6K) in cells at both ages. In the younger mononucleated myocytes, the phosphorylation of ERK and Akt was reduced in the presence of IGF-1 and T3. However, the same hormone combination led to a dramatic twofold increase in the phosphorylation of these signaling proteins in the 135 dGA cardiomyocytes-even in cells that were not proliferating. In the older cells, both mono- and binucleated cells were affected. In conclusion, fetal ovine cardiomyocytes undergo profound maturation related changes in signaling in response to T3 and IGF-1, but not to either factor alone. Differences in age-related response are likely to be related to milestones in fetal cardiac development as the myocardium prepares for ex utero life. PMID- 25128175 TI - Mitochondrial depolarization and electrophysiological changes during ischemia in the rabbit and human heart. AB - Instability of the inner mitochondrial membrane potential (DeltaPsim) has been implicated in electrical dysfunction, including arrhythmogenesis during ischemia reperfusion. Monitoring DeltaPsim has led to conflicting results, where depolarization has been reported as sporadic and as a propagating wave. The present study was designed to resolve the aforementioned difference and determine the unknown relationship between DeltaPsim and electrophysiology. We developed a novel imaging modality for simultaneous optical mapping of DeltaPsim and transmembrane potential (Vm). Optical mapping was performed using potentiometric dyes on preparations from 4 mouse hearts, 14 rabbit hearts, and 7 human hearts. Our data showed that during ischemia, DeltaPsim depolarization is sporadic and changes asynchronously with electrophysiological changes. Spatially, DeltaPsim depolarization was associated with action potential duration shortening but not conduction slowing. Analysis of focal activity indicated that DeltaPsim is not different within the myocardium where the focus originates compared with normal ventricular tissue. Overall, our data suggest that during ischemia, mitochondria maintain their function at the expense of sarcolemmal electrophysiology, but DeltaPsim depolarization does not have a direct association to ischemia-induced arrhythmias. PMID- 25128176 TI - Calibrated delivery drape versus indirect gravimetric technique for the measurement of blood loss after delivery: a randomized trial. AB - BACKGROUND: Trials of interventions for PPH prevention and treatment rely on different measurement methods for the quantification of blood loss and identification of PPH. This study's objective was to compare measures of blood loss obtained from two different measurement protocols frequently used in studies. METHODS: Nine hundred women presenting for vaginal delivery were randomized to a direct method (a calibrated delivery drape) or an indirect method (a shallow bedpan placed below the buttocks and weighing the collected blood and blood-soaked gauze/pads). Blood loss was measured from immediately after delivery for at least one hour or until active bleeding stopped. RESULTS: Significantly greater mean blood loss was recorded by the direct than by the indirect measurement technique (253.9 mL and 195.3 mL, respectively; difference = 58.6 mL (95% CI: 31-86); p < 0.001). Almost twice as many women in the direct than in the indirect group measured blood loss > 500 mL (8.7% vs. 4.7%, p = 0.02). CONCLUSIONS: The study suggests a real and significant difference in blood loss measurement between these methods. Research using blood loss measurement as an endpoint needs to be interpreted taking measurement technique into consideration. TRIAL REGISTRATION: This study has been registered at clinicaltrials.gov as NCT01885845. PMID- 25128177 TI - Long-term increased risk of unemployment after young stroke: a long-term follow up study. AB - OBJECTIVE: To investigate the prevalence, excess risk, and risk factors of unemployment in patients after a TIA, ischemic stroke, or intracerebral hemorrhage at ages 18 through 50 years, compared with nationwide controls. METHODS: We performed a hospital-based cohort study among 694 patients, aged 18 50 years, with a first-ever TIA, ischemic stroke, or intracerebral hemorrhage. After a mean follow-up duration of 8.1 (SD 7.7) years, we used logistic regression analysis to calculate odds ratio (OR) with 95% confidence interval (CI) for being unemployed as a young stroke patient, compared with the Dutch population of vocational age (n = 7,803,000), with subsequent assessment of risk factors of unemployment. RESULTS: Young stroke patients had a higher risk of being unemployed than their peers in the Dutch population: women OR 2.3 (1.8 2.9), men OR 3.2 (2.5-4.0). A higher NIH Stroke Scale score at admission (OR 1.1 [95% CI 1.0-1.1]) and a longer follow-up duration (middle tertile OR 2.8 [95% CI 1.7-4.7], upper tertile OR 3.4 [95% CI 1.9-6.1]) were associated with a higher risk of being unemployed. CONCLUSION: Young stroke patients had a 2-3 times higher risk of unemployment after 8 years of follow-up. Return-to-work programs should be developed, adjusted, and evaluated in order to diminish the negative effects that unemployment can have on patients' life satisfaction and to limit the socioeconomic consequences. PMID- 25128178 TI - Studying the brain: Complexities at every level. PMID- 25128179 TI - Predictions, perception, and a sense of self. AB - In recent years there has been a paradigm shift in theoretical neuroscience in which the brain-as a passive processor of sensory information-is now considered an active organ of inference, generating predictions and hypotheses about the causes of its sensations. In this commentary, we try to convey the basic ideas behind this perspective, describe their neurophysiologic underpinnings, and highlight the potential importance of this formulation for clinical neuroscience. The formalism it provides-and the implementation of active inference in the brain may have the potential to reveal aspects of functional neuroanatomy that are compromised in conditions ranging from Parkinson disease to schizophrenia. In particular, many neurologic and neuropsychiatric conditions may be understandable in terms of a failure to modulate the postsynaptic gain of neuronal populations reporting prediction errors during action and perception. From the perspective of the predictive brain, this represents a failure to encode the precision of-or confidence in-sensory information. We propose that the predictive or inferential perspective on brain function offers novel insights into brain diseases. PMID- 25128180 TI - Subclinical leukodystrophy and infertility in a man with a novel homozygous CLCN2 mutation. PMID- 25128181 TI - Life after stroke: Beyond medications. PMID- 25128182 TI - Central poststroke pain in young ischemic stroke survivors in the Helsinki Young Stroke Registry. AB - OBJECTIVE: We describe the frequency, duration, clinical characteristics, and radiologic correlates of central poststroke pain (CPSP) in young ischemic stroke survivors in a prospective study setting. METHODS: A questionnaire of pain and sensory abnormalities and EQ-5D quality-of-life questionnaire were sent to all 824 surviving and eligible patients of the Helsinki Young Stroke Registry. Patients (n = 58) with suspected CPSP were invited to a clinical visit and filled in the PainDETECT, Brief Pain Inventory, and Beck Depression Inventory questionnaires. RESULTS: Of the included 824 patients, 49 had CPSP (5.9%), 246 patients (29.9%) had sensory abnormality without CPSP, and 529 patients (64.2%) had neither sensory abnormality nor CPSP. The median follow-up time from stroke was 8.5 years (interquartile range 5.0-12.1). Patients with CPSP had low quality of life compared to those with sensory abnormality without CPSP (p = 0.007) as well as to those with no sensory abnormality and no CPSP (p < 0.001). Forty (82%) of the patients with CPSP had concomitant other pain. CPSP was associated with moderate (p < 0.001) and severe (p < 0.001) stroke symptoms, but there was no difference in age at stroke onset or subtype of stroke according to the TOAST classification between the groups. Stroke localization was not correlated with CPSP. CONCLUSIONS: Late persistent CPSP was found in 5.9% of young stroke survivors and was associated with concomitant other pain, impaired quality of life, and moderate or severe stroke symptoms. PMID- 25128183 TI - Course of psychiatric symptoms and global cognition in early Parkinson disease. AB - OBJECTIVE: To evaluate the course and predictors of neuropsychiatric symptoms (NPS) and cognition in patients with de novo Parkinson disease (PD). METHODS: Cross-sectional study of the cohort of de novo, untreated (at enrollment) patients with PD and healthy controls (HCs) from the Parkinson's Progression Markers Initiative. Participants have serial assessments of global cognition and symptoms of depression, anxiety, psychosis, impulse control disorders (ICDs), sleep and wakefulness, apathy, and fatigue. Available data up to 24 months of follow-up were included. RESULTS: The available sample size was as follows: baseline (PD = 423, HCs = 196), 12 months (PD = 261, HCs = 145), and 24 months (PD = 96, HCs = 83). Patients with PD experienced more depression, fatigue, apathy, and anxiety than HCs at all time points, and apathy (p = 0.001) and psychosis (p = 0.003) increased over time in patients with PD. Approximately two thirds of patients with PD who screened positive for depression at any given visit were not taking an antidepressant. The Montreal Cognitive Assessment score decreased significantly over time in patients with PD (p < 0.001), but the change was comparable to that in HCs. At the 24-month visit, 44% of patients had been on dopamine replacement therapy (DRT) for at least 1 year, and this group reported more incident ICDs (p = 0.009) and excessive daytime sleepiness (p = 0.03). CONCLUSION: Multiple NPS are more common in de novo, untreated patients with PD compared with the general population, but they also remain relatively stable in early disease, while global cognition slightly deteriorates. In contrast, initiation of DRT is associated with increasing frequency of several other NPS. PMID- 25128184 TI - Ultra-performance liquid chromatography-quadrupole?time-of- flight mass spectrometry with multivariate statistical analysis for exploring potential chemical markers to distinguish between raw and processed Rheum palmatum. AB - BACKGROUND: The long term use of Rheum palmatum for the treatment of diseases associated with chronic hepatitis and renal failure can lead to liver and kidney damage. To reduce the toxicity of R. palmatum and alleviate any symptoms of decanta and celialgia, the raw material has been subjected to a specific process prior to its use for hundreds of years. Despite its extensive use in medicine, very little is currently known about the nature of the components present in this material in terms of their efficacy and overall toxicity, and the effect that processing has on the levels of these components in the processed material. The aim of this investigation was to explore potential differences in the chemical markers between batches of raw and processed R. palmatum and to develop a deeper understanding of the underlying mechanisms responsible for the enhanced efficacy and reduced toxicity of the processed material. METHODS: Raw and processed R. palmatum samples were analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) coupled with multivariate statistical analysis using principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). RESULTS: The emodin-8-O-glucoside, emodin-O-glucoside, catechin-glucopyranoside, gallic acid-3 O-glucoside, torachrysone, and chrysophanol dimethyl ether were rapidly explored as representative markers to distinguish for the first time between the raw and processed R. palmatum material. Among the potential chemical markers, Emodin-8-O glucoside and gallic acid-3-O-glucoside were determined to be the best markers for the raw and processed R. palmatum. CONCLUSION: UPLC/Q-TOF-MS with multivariate statistical analysis represents an efficient method for exploring the chemical markers in the raw and processed R. palmatum material, as well as investigating the mechanisms associated with the processing, quality control, and safe application of R. palmatum. PMID- 25128186 TI - Family-based interventions for substance misuse: a systematic review of systematic reviews--protocol. AB - BACKGROUND: Worldwide, there are an estimated 15 million individuals with drug use disorders and over five times as many with alcohol use disorders (WHO 1:2, 2005). Most individuals with substance misuse have families who are affected. Initial scoping searches identified an expanse of broad and disparate studies and reviews on the family interventions for substance misuse. This systematic review of systematic reviews aims to bring together the expanse of research on the effectiveness of family-based interventions in substance misuse.Initial scoping searches identified an expanse of broad and disparate studies and reviews on the family interventions for substance misuse. This systematic review of systematic reviews aims to bring together the expanse of research on the effectiveness of family-based interventions in substance misuse. METHODS: Extensive electronic and manual searches will be undertaken. Screening, data extraction and quality assessment will be undertaken by two reviewers with disagreements resolved through discussion.The inclusion criteria will be that the study is a systematically undertaken review, the population is individuals with substance misuse problems and the interventions include a family-focused component. Reviews that focus on prevention rather than treatment will be excluded. The reviews will be assessed for quality and relevance. The evidence from included systematic reviews will be mapped by focus of intervention (promoting engagement of user into treatment/joint involvement in treatment of user/treating family member in own right) for both adults and adolescents for drug and/or alcohol misusers to allow assessment of the density of available evidence. The higher-quality, up-to date evidence for each domain will be identified and described, and conclusions will be drawn with limitations of the evidence highlighted. DISCUSSION: This systematic review of systematic reviews will be an efficient and robust way of looking at the current state of the evidence in the field of family-based interventions for substance misuse. It will evaluate all the available systematic review-level literature to report on the effectiveness of family-based psychological interventions in improving substance-related outcomes and improving health and wellbeing of substance misusers and/or their families. This will inform future treatment policies and commissioning decisions.In addition, it will identify areas of poor quality, inconsistency and gaps in the evidence base for family-based psychological interventions in substance misuse with respect to secondary evidence in order to inform future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014006834. PMID- 25128185 TI - Recruitment of young adults into a randomized controlled trial of weight gain prevention: message development, methods, and cost. AB - BACKGROUND: Young adulthood (age 18 to 35) is a high-risk period for unhealthy weight gain. Few studies have recruited for prevention of weight gain, particularly in young adults. This paper describes the recruitment protocol used in the Study of Novel Approaches to Prevention (SNAP). METHODS: We conducted extensive formative work to inform recruitment methods and message development. We worked with a professional marketing firm to synthesize major themes and subsequently develop age-appropriate messages for recruitment. A variety of approaches and channels were used across two clinical centers to recruit young adults who were normal or overweight (body mass index (BMI) 21 to 30 kg/m2) for a 3-year intervention designed to prevent weight gain. We tracked recruitment methods, yields, and costs by method. Logistic regression was used to identify recruitment methods that had the highest relative yield for subgroups of interest with covariate adjustments for clinic. RESULTS: The final sample of 599 participants (27% minority, 22% male) was recruited over a 19-month period of sustained efforts. About 10% of those who initially expressed interest via a screening website were randomized. The most common reason for ineligibility was already being obese (BMI >30 kg/m2). The top two methods for recruitment were mass mailing followed by email; together they were cited by 62% of those recruited. Television, radio, paid print advertising, flyers and community events each yielded fewer than 10% of study participants. Email was the most cost effective method per study participant recruited. CONCLUSIONS: These findings can guide future efforts to recruit young adults and for trials targeting weight gain prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01183689 (registered 13 August 2010). PMID- 25128187 TI - Rare embryonal rhabdomyosarcoma of external acoustic canal: a case report and literature review. AB - Embryonal rhabdomyosarcoma of external ear canal is very rare, even in the pediatric population. We report an embryonal rhabdomyosarcoma of external acoustic canal, occurring in a 12-year-old Chinese girl who presented with left ear canal mass. Wide local excision of the mass was done under local anesthesia. Histopathological examination revealed the diagnosis. She then underwent 20 cycles of radiotherapy. CECT scan post treatment showed clearance of tumor cell. Now, patient is disease free for 5 years. We believe that early diagnosis followed by complete resection of the tumor with clear margin and radiotherapy improves the prognosis of the disease. PMID- 25128188 TI - Prediction of clinical manifestations of transurethral resection syndrome by preoperative ultrasonographic estimation of prostate weight. AB - BACKGROUND: This study aimed to investigate the relationship between preoperative estimated prostate weight on ultrasonography and clinical manifestations of transurethral resection (TUR) syndrome. METHODS: The records of patients who underwent TUR of the prostate under regional anesthesia over a 6-year period were retrospectively reviewed. TUR syndrome is usually defined as a serum sodium level of < 125 mmol/l combined with clinical cardiovascular or neurological manifestations. This study focused on the clinical manifestations only, and recorded specific central nervous system and cardiovascular abnormalities according to the checklist proposed by Hahn. Patients with and without clinical manifestations of TUR syndrome were compared to determine the factors associated with TUR syndrome. Receiver operating characteristic curve analysis was used to determine the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome. RESULTS: This study included 167 patients, of which 42 developed clinical manifestations of TUR syndrome. There were significant differences in preoperative estimated prostate weight, operation time, resected prostate weight, intravenous fluid infusion volume, blood transfusion volume, and drainage of the suprapubic irrigation fluid between patients with and without clinical manifestations of TUR syndrome. The preoperative estimated prostate weight was correlated with the resected prostate weight (Spearman's correlation coefficient, 0.749). Receiver operator characteristic curve analysis showed that the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome was 75 g (sensitivity, 0.70; specificity, 0.69; area under the curve, 0.73). CONCLUSIONS: Preoperative estimation of prostate weight by ultrasonography can predict the development of clinical manifestations of TUR syndrome. Particular care should be taken when the estimated prostate weight is > 75 g. PMID- 25128189 TI - Physical and genetic interaction between ammonium transporters and the signaling protein Rho1 in the plant pathogen Ustilago maydis. AB - Dimorphic transitions between yeast-like and filamentous forms occur in many fungi and are often associated with pathogenesis. One of the cues for such a dimorphic switch is the availability of nutrients. Under conditions of nitrogen limitation, fungal cells (such as those of Saccharomyces cerevisiae and Ustilago maydis) switch from budding to pseudohyphal or filamentous growth. Ammonium transporters (AMTs) are responsible for uptake and, in some cases, for sensing the availability of ammonium, a preferred nitrogen source. Homodimer and/or heterodimer formation may be required for regulating the activity of the AMTs. To investigate the potential interactions of Ump1 and Ump2, the AMTs of the maize pathogen U. maydis, we first used the split-ubiquitin system, followed by a modified split-YFP (yellow fluorescent protein) system, to validate the interactions in vivo. This analysis showed the formation of homo- and hetero oligomers by Ump1 and Ump2. We also demonstrated the interaction of the high affinity ammonium transporter, Ump2, with the Rho1 GTPase, a central protein in signaling, with roles in controlling polarized growth. This is the first demonstration in eukaryotes of the physical interaction in vivo of an ammonium transporter with the signaling protein Rho1. Moreover, the Ump proteins interact with Rho1 during the growth of cells in low ammonium concentrations, a condition required for the expression of the Umps. Based on these results and the genetic evidence for the interaction of Ump2 with both Rho1 and Rac1, another small GTPase, we propose a model for the role of these interactions in controlling filamentation, a fundamental aspect of development and pathogenesis in U. maydis. PMID- 25128190 TI - Distribution and trends in outpatient utilization of generic versus brand name psychopharmaceuticals during a ten-year period in Croatia. AB - BACKGROUND: Drug costs increasingly pose a burden upon the otherwise inadequate health care resources and rational drug utilization is an important segment of every national health policy. Optimal patient care should be the goal of rational pharmacotherapy, whereby the economic burden of treatment is just one of the elements to be considered on choosing appropriate therapy.The aim of this study was to determine distribution and trends in the outpatient utilization of generic versus brand name psychopharmaceuticals and to evaluate the rationality of prescribing psychopharmaceuticals during a ten-year period. METHODS: Using the World Health Organization Anatomical-Therapeutic-Chemical classification/Defined Daily Doses (ATC/DDD) methodology, the number of DDD was calculated from data collected from pharmacies on the number and size of drug packages. The ratio of generic and brand name drug costs served as an indicator on assessing the rationality of drug utilization. RESULTS: Total cost for psychopharmaceuticals increased by 20.1%, more for brand name than for generic agents (32.7% vs. 7.4%). The highest share of generic psychopharmaceuticals as compared with brand name drugs according to DDD per 1000 inhabitants per day (DDD/1000/day) was in the group of psycholeptics (83.6% in 2001 vs. 82.2% in 2010), most in hypnotics and sedatives, and least in antipsychotics. The share of generic psychopharmaceuticals in total drug utilization according to financial indicators decreased by 9.6% and according to DDD/1000/day by 12%. The greatest decrease was in antidepressants, i.e. by 33.8% according to financial indicators and by 46% according to DDD/1000/day; and in antipsychotics by 30.9% according to DDD/1000/day, while showing an increase by 8.5% according to financial indicators. In the therapeutic subgroup of mood stabilizers, the share of generic drugs in total drug utilization declined by 32% according to DDD/1000/day, but increased by 25.1% according to financial indicators. CONCLUSIONS: The lack of uniform national guidelines and the still strong impact of pharmaceutical industry marketing continue favoring the rise in prescribing brand name antidepressants and antipsychotics. Depression, schizophrenia and bipolar diseases are complex diseases. As a result, specific measures are needed to encourage the prescribing of generic psychopharmaceuticals. PMID- 25128191 TI - Receiver operating characteristic curve analysis to determine the diagnostic performance of serum haptoglobin concentration for the diagnosis of acute puerperal metritis in dairy cows. AB - Acute puerperal metritis (APM) in dairy cows is characterized by fever and fetid vaginal discharge within 21 days in milk (DIM). Increased serum haptoglobin concentration (Hp) can support the diagnosis of APM. However, there is a dearth of information of the test performance of Hp as a measure for APM with a consistent definition and considering parity. The objective of this trial was to study the test performance of Hp to distinguish healthy cows from cows with APM. A total of 33 of 60 (55.0%) primiparous cows and 43 of 133 (32.3%) multiparous cows developed APM. Primiparous cows with APM had the greatest Hp. However, in primiparous cows Hp did not significantly differ between healthy cows (DIM 2: 1.49 +/- 0.64 mg/mL; DIM 5: 2.13 +/- 0.66 mg/mL; DIM 10: 1.46 +/- 0.85 mg/mL) and cows with APM (DIM 2: 1.78 +/- 0.62 mg/mL; DIM 5: 2.48 +/- 0.64 mg/mL; DIM 10: 1.60 +/- 0.81 mg/mL). In multiparous cows, Hp was greater in cows with APM (DIM 2: 1.27 +/- 0.68 mg/mL; DIM 5: 1.89 +/- 0.94 mg/mL; DIM 10: 1.23 +/- 0.78 mg/mL) than in healthy cows (DIM 2: 0.99 +/- 0.68 mg/mL; DIM 5: 1.10 +/- 0.80 mg/mL; DIM 10: 0.83 +/- 0.68 mg/mL). Sensitivity and specificity of Hp to diagnose APM in multiparous cows ranged from 72% to 79% and 54% to 71% on DIM 2, 5 and 10, respectively. PMID- 25128192 TI - Novel approaches to target NF-kappaB and other signaling pathways in cancer stem cells. AB - Recently cancer tissue is considered to consist of large number of balk cancer cells and a small number of cancer stem cells. After surgery, radiotherapy, or chemotherapy, most cancer cells are removed, but if there are still very small number of cancer stem cells left. They may form the similar tumor again. So removal of cancer stem cells is considered to be important for future cancer therapy. In one hand, NF-kappaB is the transcription factor that promotes expressions of various inflammatory cytokines and apoptosis inhibitory proteins. Cancer cells often possess constitutively activated NF-kappaB that often provides excess survival and therapeutic resistance in cancer cells. We have discovered DHMEQ as a specific inhibitor of NF-kappaB. This compound was found to be more active in cancer stem cells than in balk cancer cells. In breast cancer cells both PI3K-Akt and NF-kappaB pathways appear in the survival of cancer stem cells. PMID- 25128193 TI - Vitamin D deficiency and lower TGF-beta/IL-17 ratio in a North Indian cohort of pemphigus vulgaris. AB - BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by acantholysis of keratinocytes due to pathogenic desmoglein-3 autoantibodies. Role of vitamin D has been recently implicated in various autoimmune conditions due to its immunomodulatory effects on innate and adaptive immune responses. One of the key mechanisms of the immune regulation by vitamin D is through its anti inflammatory effects by suppression of Th17 functions. Thus, vitamin D may be involved in pathogenesis of PV. In this study, the serum vitamin D, IL-17 and TGF beta levels in PV patients as well as healthy controls were estimated in order to understand the underlying immune mechanism involved in disease pathogenesis. RESULTS: This retrospective study included 30 biopsy proven PV patients' sera. Ten age matched volunteers without any cutaneous or autoimmune conditions were recruited as healthy control (HC). Serum Vitamin D levels were measured using chemiluminescence, whereas IL-17 and TGF-beta levels were determined using ELISA. All patients showed deficient vitamin D levels (11.1 +/- 5.8 ng/ml). Moreover, all the PV patients had elevated serum IL-17 levels (210.7 +/- 105.3), whereas it was not detectable in any (n = 10) of the healthy controls sera (ELISA sensitivity >= 8 pg/ml). The mean serum TGF-beta concentration was also lower in patient sera as compared to healthy control, and the TGF-beta/IL-17 ratio was drastically reduced in patients (30.30 +/- 28), as compared to healthy controls (1363.34 +/- 559.52). CONCLUSIONS: Hypovitaminosis is common in North India, as ascertained by deficient levels in healthy controls, and was also consistently observed in PV patient. These low levels were not related to age or gender. The increased serum IL-17 and dramatic reduction in TGF-beta/IL-17 ratio in diseased patients further indicate that dysregulation of the Treg/Th-17 axis of T effector cells may be of significance in pathogenesis of PV. Thus, the study indicates that vitamin D insufficiency may be a predisposing factor in PV, contributing through its role in any of the various adaptive immune mechanisms that regulate T cell functions in vivo. Thus, there is a need to further evaluate the Treg/Th-17 axis, as it may have an important role in disease progression. PMID- 25128194 TI - Morphisms of reaction networks that couple structure to function. AB - BACKGROUND: The mechanisms underlying complex biological systems are routinely represented as networks. Network kinetics is widely studied, and so is the connection between network structure and behavior. However, similarity of mechanism is better revealed by relationships between network structures. RESULTS: We define morphisms (mappings) between reaction networks that establish structural connections between them. Some morphisms imply kinetic similarity, and yet their properties can be checked statically on the structure of the networks. In particular we can determine statically that a complex network will emulate a simpler network: it will reproduce its kinetics for all corresponding choices of reaction rates and initial conditions. We use this property to relate the kinetics of many common biological networks of different sizes, also relating them to a fundamental population algorithm. CONCLUSIONS: Structural similarity between reaction networks can be revealed by network morphisms, elucidating mechanistic and functional aspects of complex networks in terms of simpler networks. PMID- 25128195 TI - Prokineticin 1 and leukemia inhibitory factor mRNA expression in the endometrium of women with idiopathic recurrent pregnancy loss. AB - OBJECTIVE: To determine the expression patterns of prokineticin 1 (PROK1) and leukemia inhibitory factor (LIF) mRNA differ in peri-implantation endometrial tissue of women with idiopathic recurrent pregnancy loss (RPL) from normal fertile women. DESIGN: A case-control study. SETTING: University-based tertiary care center. PATIENT(S): 30 women with idiopathic RPL and 30 fertile controls. INTERVENTION(S): Endometrial biopsies. MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction analysis for expression of PROK1 and LIF mRNA. RESULT(S): The expression of PROK1 and LIF was statistically significantly increased in the endometrium of the women with idiopathic RPL compared with the controls. Furthermore, increased LIF expression was observed in the endometrium of women with idiopathic RPL compared with controls. CONCLUSION(S): An increased mRNA expression of PROK1 and LIF could be one of the several abnormalities characterizing the endometrium in women with RPL. PMID- 25128196 TI - BESST--efficient scaffolding of large fragmented assemblies. AB - BACKGROUND: The use of short reads from High Throughput Sequencing (HTS) techniques is now commonplace in de novo assembly. Yet, obtaining contiguous assemblies from short reads is challenging, thus making scaffolding an important step in the assembly pipeline. Different algorithms have been proposed but many of them use the number of read pairs supporting a linking of two contigs as an indicator of reliability. This reasoning is intuitive, but fails to account for variation in link count due to contig features.We have also noted that published scaffolders are only evaluated on small datasets using output from only one assembler. Two issues arise from this. Firstly, some of the available tools are not well suited for complex genomes. Secondly, these evaluations provide little support for inferring a software's general performance. RESULTS: We propose a new algorithm, implemented in a tool called BESST, which can scaffold genomes of all sizes and complexities and was used to scaffold the genome of P. abies (20 Gbp). We performed a comprehensive comparison of BESST against the most popular stand alone scaffolders on a large variety of datasets. Our results confirm that some of the popular scaffolders are not practical to run on complex datasets. Furthermore, no single stand-alone scaffolder outperforms the others on all datasets. However, BESST fares favorably to the other tested scaffolders on GAGE datasets and, moreover, outperforms the other methods when library insert size distribution is wide. CONCLUSION: We conclude from our results that information sources other than the quantity of links, as is commonly used, can provide useful information about genome structure when scaffolding. PMID- 25128197 TI - Shaping zoonosis risk: landscape ecology vs. landscape attractiveness for people, the case of tick-borne encephalitis in Sweden. AB - BACKGROUND: In this paper, the hazard and exposure concepts from risk assessment are applied in an innovative approach to understand zoonotic disease risk. Hazard is here related to the landscape ecology determining where the hosts, vectors and pathogens are and, exposure is defined as the attractiveness and accessibility to hazardous areas. Tick-borne encephalitis in Sweden was used as a case study. METHODS: Three boosted regression tree models are compared: a hazard model, an exposure model and a global model which combines the two approaches. RESULTS: The global model offers the best predictive power and the most accurate modelling. The highest probabilities were found in easy-to-reach places with high landscape diversity, holiday houses, waterbodies and, well-connected forests of oak, birch or pine, with open-area in their ecotones, a complex shape, numerous clear-cuts and, a variation in tree height. CONCLUSION: While conditions for access and use of hazardous areas are quite specific to Scandinavia, this study offers promising perspectives to improve our understanding of the distribution of zoonotic and vector-borne diseases in diverse contexts. PMID- 25128198 TI - Evaluation of anterior segment parameters during and after pregnancy. AB - PURPOSE: To compare the anterior segment parameters during pregnancy and post pregnancy. MATERIALS AND METHODS: Fifty-four healthy pregnant women in their third trimester with ages ranging from 18 to 38 years were included in the study. All of the patients underwent comprehensive ophthalmologic examinations, including refraction, anterior segment, and fundus examinations, intraocular pressure, and axial length measurements. In addition, anterior chamber angle, anterior chamber depth, anterior chamber volume, corneal volume, central corneal thickness, and keratometry values were measured by Pentacam Scheimpflug camera. All measurements were measured again 3 months after delivery. RESULTS: The mean intraocular pressure, anterior chamber angle, anterior chamber depth, anterior chamber volume, corneal volume, central corneal thickness, and keratometry measurements were significantly different during pregnancy and post-pregnancy (p<0.05 for all); however, the mean spherical refraction, cylindrical refraction, and axial length were not statistically significantly different during pregnancy and post-pregnancy (p>0.05 for all). CONCLUSIONS: We found that there is an increase in the anterior chamber parameters, corneal volume, corneal thickness, and corneal curvature and a decrease in intraocular pressure in the third trimester. PMID- 25128199 TI - Tumour necrosis factor, interleukin-6 and interleukin-10 are possibly involved in Plasmodium vivax-associated thrombocytopaenia in southern Pakistani population. AB - BACKGROUND: In Pakistan, Plasmodium vivax is endemic causing approximately 70% of the malaria cases. A number of haematological changes, especially thrombocytopaenia have been reported for P. vivax. Several host factors including cell-mediated immune cells, such as IL-1, IL-6 and IL-10 have been documented for P. vivax-induced thrombocytopaenia. However, study on correlation of cytokines and thrombocytopaenia in P. vivax, particularly in patients with severe signs and symptoms has not been reported from Pakistan. METHODS: A case control study to correlate TNF, IL-6 and IL-10 in healthy controls and thrombocytopaenic P. vivax infected patients (both uncomplicated and complicated cases) from southern Pakistan was carried out during January 2009 to December 2011. One Hundred and eighty two patients presenting with microscopy-confirmed asexual P. vivax mono infection and 100 healthy controls were enrolled in the study at Aga Khan University Hospital, Karachi. Enzyme-linked immunosorbent assay (ELISA) was performed for determination of TNF, IL-6 and IL-10 levels. RESULTS: Out of 182 cases, mild thrombocytopaenia (platelet count 100,000-150,000 mm3) was observed in ten (5.5%), moderate (50,000-100,000 mm3) in 93 (51.1%), and profound thrombocytopaenia (<50,000 mm3) was detected in 79 (43.4%) patients. IL-6 and IL 10 levels were found approximately three-fold higher in the mild cases compared to healthy controls. Two-fold increase in TNF and IL-10 (p < 0.0001) was observed in profound thrombocytopaenic when compared with moderate cases, while IL-6 was not found to be significantly elevated. CONCLUSION: Cytokines may have a possible role in P. vivax-induced thrombocytopaenia in Pakistani population. Findings from this study give first insight from Pakistan on the role of cytokines in P.vivax associated thrombocytopaenia. However, further studies are required to understand the relevance of cytokines in manifestations of thrombocytopaenia in P. vivax malaria. PMID- 25128200 TI - Sequence analysis of porothramycin biosynthetic gene cluster. AB - The biosynthetic gene cluster of porothramycin, a sequence-selective DNA alkylating compound, was identified in the genome of producing strain Streptomyces albus subsp. albus (ATCC 39897) and sequentially characterized. A 39.7 kb long DNA region contains 27 putative genes, 18 of them revealing high similarity with homologous genes from biosynthetic gene cluster of closely related pyrrolobenzodiazepine (PBD) compound anthramycin. However, considering the structures of both compounds, the number of differences in the gene composition of compared biosynthetic gene clusters was unexpectedly high, indicating participation of alternative enzymes in biosynthesis of both porothramycin precursors, anthranilate, and branched L-proline derivative. Based on the sequence analysis of putative NRPS modules Por20 and Por21, we suppose that in porothramycin biosynthesis, the methylation of anthranilate unit occurs prior to the condensation reaction, while modifications of branched proline derivative, oxidation, and dimethylation of the side chain occur on already condensed PBD core. Corresponding two specific methyltransferase encoding genes por26 and por25 were identified in the porothramycin gene cluster. Surprisingly, also methyltransferase gene por18 homologous to orf19 from anthramycin biosynthesis was detected in porothramycin gene cluster even though the appropriate biosynthetic step is missing, as suggested by ultra high-performance liquid chromatography-diode array detection-mass spectrometry (UHPLC-DAD-MS) analysis of the product in the S. albus culture broth. PMID- 25128201 TI - A cross-sectional analysis of the relationship between uric acid and coronary atherosclerosis in patients with suspected coronary artery disease in China. AB - BACKGROUND: Although many studies have examined the relationship between uric acid (UA) and coronary artery disease (CAD), whether UA is an independent risk factor contributing to progression of CAD is still controversial. Whether UA plays a different role in different sexes is also unclear. METHODS: A total of 1116 individuals with suspected CAD were stratified into four groups according to their serum UA quartiles in total (men and women combined), in men, and in women. The association of UA with coronary atherosclerosis was assessed by univariable and multivariable logistic regression. RESULTS: In total and in women, the prevalence of any plaques and significant/severe stenosis was significantly increased with an increase in quartiles of UA (all P < 0.05). The proportion of triple-vessel disease and left main artery lesion was highest in the fourth quartile (both p < 0.05). Increasing quartiles of UA were significantly associated with a coronary artery calcium score (CACS) >10 (all P < 0.01). As UA levels increased in women, the incidence of double-vessel lesions (p = 0.017) and the proportion of mixed plaques (p = 0.022) were significantly increased. The proportion of a CACS of 0 in total, in men and women was highest in the first quartile (all P < 0.01). UA was the strongest predictor of significant stenosis, multivessel disease, and mixed plaques in women (all p < 0.05). UA was the only risk factor for mixed plaques in total (P = 0.046). CONCLUSION: The level of UA was significantly associated with coronary atherosclerosis in women, but not men. PMID- 25128202 TI - The radiosensitising effect of gemcitabine and its main metabolite dFdU under low oxygen conditions is in vitro not dependent on functional HIF-1 protein. AB - BACKGROUND: Regions within solid tumours often experience oxygen deprivation, which is associated with resistance to chemotherapy and irradiation. The aim of this study was to evaluate the radiosensitising effect of gemcitabine and its main metabolite dFdU under normoxia versus hypoxia and to determine whether hypoxia-inducible factor 1 (HIF-1) is involved in the radiosensitising mechanism. METHODS: Stable expression of dominant negative HIF-1alpha (dnHIF) in MDA-MB-231 breast cancer cells, that ablated endogenous HIF-1 transcriptional activity, was validated by western blot and functionality was assessed by HIF-1alpha activity assay. Cells were exposed to varying oxygen environments and treated with gemcitabine or dFdU for 24 h, followed by irradiation. Clonogenicity was then assessed. Using radiosensitising conditions, cells were collected for cell cycle analysis. RESULTS: HIF-1 activity was significantly inhibited in cells stably expressing dnHIF. A clear radiosensitising effect under normoxia and hypoxia was observed for both gemcitabine and dFdU. No significant difference in radiobiological parameters between HIF-1 proficient and HIF-1 deficient MDA-MB 231 cells was demonstrated. CONCLUSIONS: For the first time, radiosensitisation by dFdU, the main metabolite of gemcitabine, was demonstrated under low oxygen conditions. No major role for functional HIF-1 protein in radiosensitisation by gemcitabine or dFdU could be shown. PMID- 25128204 TI - Identifying factors of bicycle comfort: An online survey with enthusiast cyclists. AB - Racing bicycles have evolved significantly over the past decades as technology and cyclists' comfort have become a critical design issue. Although ample research has been conducted on comfort for other means of transportation, cyclists' perception of dynamic comfort has received scant attention in the scientific literature. The present study investigates how enthusiast cyclists conceptualize comfort using an online survey with 244 respondents. The purpose is to determine which factors contribute to comfort when riding a bicycle, to identify situations in which comfort is relevant and to determine the extent to which vibrations play a role in comfort evaluations. We found that comfort is influenced by factors related to bicycle components (specifically the frame, saddle and handlebar), as well as environmental factors (type or road, weather conditions) and factors related to the cyclist (position, adjustments, body parts). Respondents indicated that comfort is a concern when riding a bicycle in most situations and they believed that comfort is compatible with performance. The PCA analysis shows that for the perception "human factor-body parts" are put in evidence, and the "cyclist's comfort" evaluation is mainly based on certain qualities related to the bicycle components, then the road and external conditions (e.g. weather, temperature). PMID- 25128203 TI - Strength training reduces circulating interleukin-6 but not brain-derived neurotrophic factor in community-dwelling elderly individuals. AB - Ageing is associated with a chronic low-grade inflammatory profile (CLIP). Physical exercise could circumvent the deleterious effects of CLIP by influencing circulating inflammatory mediators and neurotrophic growth factors. This study aimed at assessing whether 12 weeks of progressive strength training (PST) influences circulating brain-derived neurotrophic factor (BDNF), interleukin (IL) 6 and IL-10 in elderly individuals. Forty community-dwelling persons aged 62-72 years participated. Twenty participants were assigned to 12-week PST (70-80 % of maximal strength, three times per week). Matched control individuals (n = 20) maintained daily activity levels. Serum was collected for BDNF, IL-6 and IL-10 assay from all participants before and after 12 weeks (for PST subjects 24-48 h after the last training). In PST, muscle strength was significantly improved (+49 % for leg extension, p = 0.039), and basal IL-6 levels significantly reduced (p = 0.001), which remained unchanged in control (p = 0.117). No significant change in BDNF was observed in PST subjects (p = 0.147) or control (p = 0.563). IL-10 was below the detection limit in most subjects. Gender and health status did not influence the results. Our results show that after 12-week PST, muscle performance improved significantly, and basal levels of IL-6 were significantly decreased in older subjects. However, serum BDNF was not altered. The lack of an observable change in BDNF might be due to a short-lived BDNF response, occurring acutely following exercise, which might have been washed out when sampling. Furthermore, blood levels of BDNF may not reflect parallel increases that occur locally in the brain and muscle. These hypotheses need confirmation by further studies. PMID- 25128205 TI - The WERCAP Screen and the WERC Stress Screen: psychometrics of self-rated instruments for assessing bipolar and psychotic disorder risk and perceived stress burden. AB - BACKGROUND: Identification of individuals in the prodromal phase of bipolar disorder and schizophrenia facilitates early intervention and promises an improved prognosis. There are no current assessment tools for clinical risk symptoms of bipolar disorder, and psychosis-risk assessment generally involves semi-structured interviews, which are time consuming and rater dependent. We present psychometric data on two novel quantitative questionnaires: the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen for assessing bipolar and psychotic disorder risk traits, and the accompanying WERC Stress Screen for assessing individual and total psychosocial stressor severities. METHODS: Prevalence rates of the WERCAP Screen were evaluated among 171 community youth (aged 13-24 years); internal consistency was assessed and k means cluster analysis was used to identify symptom groups. In 33 participants, test-retest reliability coefficients were assessed, and ROC curve analysis was used to determine the validity of the psychosis section of the WERCAP Screen (pWERCAP) against the Structured Interview of Psychosis-Risk Symptoms (SIPS). Correlations of the pWERCAP, the affectivity section of the WERCAP Screen (aWERCAP) and the WERC Stress Screen were examined to determine the relatedness of scores with cognition and clinical measures. RESULTS: Cluster analysis identified three groups of participants: a normative (47%), a psychosis affectivity (18%) and an affectivity only (35%) group. Internal consistency of the aWERCAP and pWERCAP resulted in alphas of 0.87 and 0.92, and test-retest reliabilities resulted in intraclass correlation coefficients of 0.76 and 0.86 respectively. ROC curve analysis showed the optimal cut-point on the pWERCAP as a score of >30 (sensitivity: 0.89; specificity: 1.0). There was a significant negative correlation between aWERCAP scores and total cognition (R=-0.42), and between pWERCAP scores and sensorimotor processing speed. Total stress scores correlated significantly with scores on the aWERCAP (R=0.88), pWERCAP (R=0.62) and total cognition (R=-0.44). CONCLUSIONS: Our results show that the WERCAP Screen and the WERC Stress Screen are easy to administer and derived scores are related to cognitive and clinical traits. This suggests that their use could have particular benefits for epidemiologic studies and in busy clinical settings. Longitudinal studies would be required to evaluate clinical outcomes with high questionnaire scores. PMID- 25128206 TI - The reliability of biomechanical variables collected during single leg squat and landing tasks. AB - INTRODUCTION: The aim of this study was to determine the within- and between-day reliability of lower limb biomechanical variables collected during single leg squat (SLS) and single leg landing (SLL) tasks. METHODS: 15 recreational athletes took part in three testing sessions, two sessions on the same day and another session one week later. Kinematic and kinetic data was gathered using a ten camera movement analysis system (Qualisys) and a force platform (AMTI) embedded into the floor. RESULTS: The combined averages of within-day ICC values (ICCSLS=0.87; ICCSLL=0.90) were higher than between-days (ICCSLS=0.81; ICCSLL=0.78). Vertical GRF values (ICCSLS=0.90; ICCSLL=0.98) were more reliable than joint angles (ICCSLS=0.85; ICCSLL=0.82) and moments (ICCSLS=0.83; ICCSLL=0.87). DISCUSSION: This study demonstrates that all joint angles, moments, and vertical ground reaction force (GRF) variables obtained during both tasks showed good to excellent consistency with relatively low standard error of measurement values. These findings would be of relevance to practitioners who are using such measures for screening and prospective studies of rehabilitative techniques. PMID- 25128208 TI - Item-properties may influence item-item associations in serial recall. AB - Attributes of words, such as frequency and imageability, can influence memory for order. In serial recall, Hulme, Stuart, Brown, and Morin (Journal of Memory and Language, 49(4), 500-518, 2003) found that high-frequency words were recalled worse, and low-frequency words better, when embedded in alternating lists than pure lists. This is predicted by associative chaining, wherein each recalled list item becomes a recall-cue for the next item. However, Hulme, Stuart, Brown, and Morin (Journal of Memory and Language, 49(4), 500-518, 2003) argued their findings supported positional-coding models, wherein items are linked to a representation of position, with no direct associations between items. They suggested their serial-position effects were due to pre-experimental semantic similarity between pairs of items, which depended on frequency, or a complex tradeoff between item- and order-coding (Morin, Poirier, Fortin, & Hulme, Psychonomic Bulletin Review, 13(4), 724-729, 2006). We replicated the smooth serial-position effects, but accounts based on pre-existing similarity or item order tradeoffs were untenable. Alternative accounts based, on imageability, phonological and lexical neighbourhood sizes were also ruled out. The standard chaining account predicts that if accuracy is conditionalized on whether the prior item was correct, the word-frequency effect should reappear in alternating lists; however, this prediction was not borne out, challenging this retrieval based chaining account. We describe a new account, whereby frequency influences the strengths of item-item associations, symmetrically, during study. A manipulation of word-imageability also produced a pattern consistent with item item cueing at study, but left room for effects of imageability at the final stage of recall. These findings provide further support for the contribution of associative chaining to serial-recall behaviour and show that item-properties may influence serial-recall in multiple ways. PMID- 25128209 TI - Effects of difficulty, specificity, and variability on training to follow navigation instructions. AB - To study the relative merits of three training principles - difficulty of training, specificity of training, and variability of training - subjects were trained to follow navigation instructions to move in a grid on a computer screen. Subjects repeated and then followed the instructions by mouse clicking on the grid. They were trained, given a short distractor task, and then tested. There were three groups, each receiving different message lengths during training: easy (short lengths), hard (long lengths), and mixed (all lengths), with all subjects given all lengths at test. At test, the mixed group was best on most lengths, the easy group was better than the hard group on short lengths, and the hard group was better than the easy group on long lengths. The results support the advantages of both specificity and variability of training but do not support the hypothesis that difficult training of the form used here would lead to overall best performance at test. PMID- 25128210 TI - Evaluating the cost-effectiveness of preventive zinc supplementation. AB - BACKGROUND: Even though the WHO currently recommends zinc for diarrhea management, no consensus has been reached with respect to routine distribution of zinc for preventive reasons. We reviewed the health impact of preventive zinc interventions, and evaluated the relative cost effectiveness of currently feasible interventions. METHODS: Using the latest relative risk estimates reported in the literature, we parameterized a health impact model, and calculated the expected benefits of zinc supplementation in a representative low income country. We then computed the cost and cost-effectiveness for three delivery mechanisms: the direct distribution of zinc supplements, the distribution of micronutrient biscuits including zinc, and the distribution of zinc through water filtration systems. RESULTS: Combining all health outcomes and impact estimates, we find that systematic zinc supplementation among children of ages one to five would avert 1.423 DALYs per 100 households and year in least developed countries. The estimated cost per DALY is US$ 606 for pill supplementation, US$ 1211 for micronutrient biscuits, and US$ 879 per DALY saved for water filtration systems. CONCLUSIONS: Preventive zinc supplementation to children of ages 1-5 appears to be a highly cost-effective intervention in typical developing country settings. More research will be needed to determine the most effective mechanism to deliver zinc to this target population. PMID- 25128211 TI - Evaluation of the impact of a school gardening intervention on children's fruit and vegetable intake: a randomised controlled trial. AB - BACKGROUND: Current academic literature suggests that school gardening programmes can provide an interactive environment with the potential to change children's fruit and vegetable intake. This is the first cluster randomised controlled trial (RCT) designed to evaluate whether a school gardening programme can have an effect on children's fruit and vegetable intake. METHODS: The trial included children from 23 schools; these schools were randomised into two groups, one to receive the Royal Horticultural Society (RHS)-led intervention and the other to receive the less involved Teacher-led intervention. A 24-hour food diary (CADET) was used to collect baseline and follow-up dietary intake 18 months apart. Questionnaires were also administered to evaluate the intervention implementation. RESULTS: A total of 641 children completed the trial with a mean age of 8.1 years (95% CI: 8.0, 8.4). The unadjusted results from multilevel regression analysis revealed that for combined daily fruit and vegetable intake the Teacher-led group had a higher daily mean change of 8 g (95% CI: -19, 36) compared to the RHS-led group -32 g (95% CI: -60, -3). However, after adjusting for possible confounders this difference was not significant (intervention effect: -40 g, 95% CI: -88, 1; p = 0.06). The adjusted analysis of process measures identified that if schools improved their gardening score by 3 levels (a measure of school gardening involvement - the scale has 6 levels from 0 'no garden' to 5 'community involvement'), irrespective of group allocation, children had, on average, a daily increase of 81 g of fruit and vegetable intake (95% CI: 0, 163; p = 0.05) compared to schools that had no change in gardening score. CONCLUSIONS: This study is the first cluster randomised controlled trial designed to evaluate a school gardening intervention. The results have found very little evidence to support the claims that school gardening alone can improve children's daily fruit and vegetable intake. However, when a gardening intervention is implemented at a high level within the school it may improve children's daily fruit and vegetable intake by a portion. Improving children's fruit and vegetable intake remains a challenging task. TRIAL REGISTRATION: ISRCTN11396528. PMID- 25128212 TI - Guidelines for the diagnosis and treatment of adrenal insufficiency in the adult. AB - Adrenal insufficiency (AI) is a disease characterized by a deficient production or action of glucocorticoids, with or without deficiency in mineral corticoids and/or adrenal androgens. It can result from disease intrinsic to the adrenal cortex (primary AI), from pituitary diseases that hamper the release of corticotropin (secondary AI) or from hypothalamic disorders that impair the secretion of the corticotropin-releasing hormone (tertiary AI). It is a disease with a low prevalence but its impact on the affected individual is very high as it can be life-threathening if not treated or lead to health problems if inadequately treated. However, currently there are no specific guidelines for the management of this disease. Therefore, at the proposal of the Spanish Society of Endocrinology and Nutrition (SEEN) board, a task-force under the Neuroendocrinology Knowledge Area of the SEEN was established, with the mandate of updating the diagnosis and treatment of AI. In fulfilment of this mandate the task-force has elaborated the present guide that, based on a comprehensive review of literature, is intended to provide an answer to questions related to the management of this disease. It is, therefore, an essentially practical document, mainly aimed at guiding the health professionals involved in the care of IA patients. PMID- 25128213 TI - Is there still a role for bilobed/bipaddled pectoralis major myocutaneous flap for single-stage immediate reconstruction of post ablative oncologic full thickness defects of the cheek? AB - INTRODUCTION: Reconstruction of full-thickness defects of the head and neck is a challenge. In this clinical study, we assessed the role of the bilobed/bipaddled pectoralis major myocutaneous flap (PMMF) for the reconstruction of large full thickness defects of the cheek, after resection of oral cancer. MATERIALS AND METHOD: After resection of oral cancer, 62 cases of through-and-through defects of the oral cavity were reconstructed using folded/bipaddled/bilobed PMMF flap. All were males and presented with locally advanced oral squamous cell carcinoma (SCC), which involved the buccal mucosa and gingivo buccal sulcus (n = 53) and gingivo buccal sulcus + lip (n = 9). RESULTS: All the flaps survived, and no patient developed a major complication. The most common complication in the current series was wound dehiscence. In 8% of cases, wound dehiscence was found at the donor site; in 6.45% of cases, dehiscence was present at the recipient site; and in 4.83% of cases, dehiscence was present at the neck. All the wounds healed secondarily with regular dressings. CONCLUSION: The bilobed/bipaddled PMMF is a straightforward and reliable flap that provides an effective mechanism to reconstruct full-thickness cheek defects while avoiding the complexity of microvascular free flaps. The bilobed/bipaddled PMMF has become our preferred reconstruction option for large full-thickness defects after resection of oral carcinoma. PMID- 25128214 TI - Fluoroscopic findings post-peroral esophageal myotomy. AB - Natural orifice transluminal endoscopic surgery (NOTES) is a surgical technique that has been evolving rapidly. Endoscopic submucosal dissection was initiated in 1999, in Japan, for en-bloc resection of large lesions of the stomach (Zhou et al., World J Gastroenterol 19:6962-6968, 2013, ; Kobara et al., Clin Exp Gastroenterol 7:67-74, 2014). Since then, many additional therapies utilizing natural transluminal endoscopic approach have evolved. Peroral endoscopic myotomy (POEM) is a minimally invasive type of transluminal endoscopic surgery that was recently developed for the treatment of achalasia and esophageal motility disorders. The peroral endoscopic myotomy is a less invasive surgical treatment that is suitable for all types of achalasia and used as an alternate to the Heller myotomy. The radiographic findings of achalasia and surgical changes after Heller myotomy have been described, however, very little is available on the post POEM esophagram appearance. The purpose of this article is to illustrate the anatomy, surgical procedure, and normal and abnormal findings seen on esophagrams in patients who have undergone a POEM. PMID- 25128215 TI - Pediatric sialadenitis. AB - Sialadenitis in the pediatric population accounts for up to 10% of all salivary gland disease. Viral parotitis and juvenile recurrent parotitis are the two most common causes. Multiple factors, independently or in combination, can result in acute, chronic, or recurrent acute salivary gland inflammation. Sialendoscopy has emerged as the leading diagnostic technique and intervention for pediatric sialadenitis. Sialendoscopy is a safe and effective gland-preserving treatment of pediatric sialadenitis. Investigational studies are needed to address the impact of steroid instillation, postoperative stenting, and long-term outcomes of pediatric sialendoscopy. This article presents a comprehensive review of pathophysiology, clinical presentation, diagnosis, and treatment of pediatric sialadenitis. PMID- 25128216 TI - ABT-724 alleviated hyperactivity and spatial learning impairment in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder. AB - Dysfunction of dopamine D4 receptor (D4R) is linked to attention deficit/hyperactivity disorder (ADHD) as well as ADHD associated cognitive impairment. Here, we tested the possible therapeutic benefit of the D4R-selective agonist ABT-724 in adolescent spontaneously hypertensive rats (SHRs). ABT-724 treated SHRs were administered ABT-724 (0.04mg/kg, 0.16mg/kg or 0.64mg/kg) from postnatal day (P) 28 to P32. Control SHRs and Sprague-Dawley (SD) rats were injected with saline. Then two cohorts of rats were tested in the open field and Lat maze that measured locomotion and non-selective attention (NSA), respectively. Another cohort of rats was subjected to water maze task for evaluation of spatial learning and memory. We found that control SHRs displayed hyperactivity as well as impaired NSA and spatial learning compared with normotensive SD rats. ABT-724 (0.16 and 0.64mg/kg) treatment alleviated hyperactivity and spatial learning impairment in SHRs. No dose of ABT-724 tested altered NSA in SHRs. Our results raise the possibility that ABT-724 may be used as a therapeutic intervention for ADHD patients during adolescence. PMID- 25128217 TI - Trigemino-cervical reflex in spinal cord injury. AB - Abnormal enhancement of polysynaptic brainstem reflexes has been previously reported in patients with spinal cord injury (SCI). We aimed to investigate trigemino-cervical reflex (TCR) in SCI since it may reflect alterations in the connections of trigeminal proprioceptive system and cervical motoneurons. Consecutive 14 patients with SCI and 16 healthy subjects were included in this study. All patients were in the chronic phase. TCR was recorded over sternocleidomastoid (SCM) and splenius capitis (SC) muscles by stimulation of infraorbital nerve. We measured onset latency, amplitudes and durations of responses and compared between groups. We obtained stable responses over both muscles after one sided stimulation in healthy volunteers whereas probability of TCR was decreased in patients over both SCM (78.6% vs. 100%, p=0.050) and SC (71.4% vs. 100%, p=0.022). The absence of TCR was related to use of oral baclofen (>=50mg/day). However, when present, responses of SCI group had higher amplitudes and were more persistent. We demonstrated that TCR probability was similar to healthy subjects in SCI patients who used no or low dose oral baclofen. But it had higher amplitudes and longer durations. It was not obtained in only two patients who used oral baclofen more than 50mg/day. PMID- 25128218 TI - Morphine and oxycodone, but not fentanyl, exhibit antinociceptive effects mediated by G-protein inwardly rectifying potassium (GIRK) channels in an oxaliplatin-induced neuropathy rat model. AB - It has begun to be understood that MU-opioid receptor (MOR) produces ligand biased agonism, which contributes to differential physiological functions of MOR agonists. We previously demonstrated that in oxaliplatin-induced neuropathy in rats, morphine and oxycodone exhibited antinociceptive effects while antinociception of fentanyl was partial, and such different efficacies might result from the different level of Gi/o protein activation. Based on our background, to reveal further mechanism, we focused on the role of Gi/o protein related downstream signaling, the G-protein inwardly rectifying K(+)1 (GIRK1) channel. The GIRK1 channel blocker tertiapin-Q (30pmol) was intracerebroventricularly (i.c.v.) or intrathecally (i.t.) administered to rats with oxaliplatin-induced neuropathy. The antinociception of systemic morphine (3mg/kg, subcutaneously (s.c.)) was suppressed only by pretreatment of i.t. tertiapin-Q, while supraspinal tertiapin-Q suppressed only the antinociception of systemic oxycodone (0.56mg/kg, s.c.). Partial antinocicpetion of fentanyl (0.017mg/kg, s.c.) was neither affected by i.c.v nor i.t. tertiapin-Q. These results demonstrated that GIRK1 channels differentially contribute to antinociceptive effects of MOR agonists, and that action site of GIRK1 channels is also different between morphine and oxycodone in oxaliplatin model. This study suggests the possibility that GIRK1 channels have a crucial role for antinociception of MOR agonists in oxaliplatin-induced neuropathy. PMID- 25128219 TI - Neural activity analysis of pure chito-oligomer components separated from a mixture of chitooligosaccharides. AB - Chitooligosaccharides (COSs) are obtained from the in vivo and in vitro degradation of chitosan, which is a natural biomaterial used successfully for peripheral nerve repair. Also, COSs have been reported to be beneficial for the nervous system and especially able to promote peripheral nerve regeneration. To determine which component in a mixture of COSs was really responsible for the neurotrophic action of COSs, this study was performed to separate the active components of COSs and compare the neural activity of different pure components. Hydrophilic interaction liquid chromatography (HILIC) was used to separate 5 chito-oligomers with single degrees of polymerization (DPs) from a mixture of COSs. They were chitobiose, chitotriose, chitotetraose, chitopentaose, and chitohexaose with DPs of 2-6, respectively. MTT assay indicated that chitotriose induced the greatest increase in Schwann cell survival among 5 chito-oligomers. Immunocytochemistry with anti-NF-200 showed that chitotriose significantly encouraged neurite outgrowth from dorsal root ganglion (DRG) explants with the greatest effect among 5 chito-oligomers. Our results suggest that chitotriose may be a key component in COSs mixture. PMID- 25128220 TI - In-flight rupture of breast implant pocket. PMID- 25128221 TI - Blepharoplasty techniques in the management of orbito-temporal neurofibromatosis. AB - We aimed to present blepharoplasty techniques we used for severe orbito-temporal neurofibromatosis (NF). A retrospective noncomparative single-center case study was undertaken on patients with orbito-temporal NF. Twenty-two patients with orbito-temporal NF treated at the Department of Ophthalmology of Shanghai Ninth People's Hospital between 2007 and 2011 participated in the study. They underwent a standard ophthalmologic assessment for orbito-temporal NF involving both the orbito-temporal soft tissue and bony orbits. The orbits were examined with three dimensional computed tomography (CT) and all 22 patients underwent tumor debulking, blepharoplasty, and orbital reconstruction. We modified the conventional procedures. Our reconstructive techniques included eyelid reduction; lateral canthal reattachment; for patients with collapse of the lateral orbital margin, reconstruction of the orbital margin to be performed before reattaching the lateral canthus to the implanted titanium mesh; anterior levator resection; and frontalis suspension according to preoperative levator muscle function. Visual acuity, tumor recurrence, and postoperative palpebral fissure and orbital appearance were evaluated to assess outcomes. Acceptable cosmetic results were obtained in 22 patients after debulking of the orbito-temporal NF and surgical reconstruction. There was no loss of vision or visual impairment postoperatively. All patients did not display recrudescence after a follow-up period of >1 year. Three patients with residual ptosis were successfully treated with a second ptosis repair. We believe that the blepharoplasty techniques described in the treatment of orbito-palpebral NF may provide both functional and esthetic benefits. PMID- 25128222 TI - The effect of deployment to a combat zone on testosterone levels and the association with the development of posttraumatic stress symptoms: A longitudinal prospective Dutch military cohort study. AB - OBJECTIVE: There is limited evidence on the association of the activity of HPG axis with stress and symptoms of stress-related disorders. The aim of the current study was to assess the effect of deployment to a combat zone on plasma testosterone levels, and the possible association with the development of symptoms of posttraumatic stress disorder (PTSD). METHODS: A total of 918 males were included in the study before deployment to a combat zone in Afghanistan. The effect of deployment on testosterone was longitudinally assessed; starting prior to deployment and follow-up assessments were preformed at 1 and 6 months after return. Furthermore, the association with PTSD symptoms reported at 1 and 2 years post-deployment was assessed. RESULTS: Plasma testosterone levels were significantly increased after deployment compared with pre-deployment levels. Although no difference was found between individuals reporting high or low levels of PTSD symptoms, pre-deployment testosterone levels predicted the development of PTSD symptoms at 1 and 2 years post-deployment. CONCLUSION: This study provides evidence that not the alterations in testosterone levels shortly after deployment, but the pre-deployment testosterone levels are associated with PTSD symptoms, which is of value in the identification of biological vulnerability factors for the development of PTSD. PMID- 25128223 TI - Growth, bone health, and later outcomes in infants born preterm. PMID- 25128224 TI - Taking care of the caretakers to enhance antiretroviral adherence in HIV-infected children and adolescents. PMID- 25128225 TI - The relationships between insomnia, sleep apnoea and depression: findings from the American National Health and Nutrition Examination Survey, 2005-2008. AB - OBJECTIVE: To determine the association between insomnia, obstructive sleep apnoea (OSA), and comorbid insomnia-OSA and depression, while controlling for relevant lifestyle and health factors, among a large population-based sample of US adults. METHOD: We examined a sample of 11,329 adults (>=18 years) who participated in the National Health and Nutrition Examination Survey (NHANES) during the years 2005-2008. Insomnia was classified via a combination of self reported positive physician diagnosis and high-frequency 'trouble falling asleep', 'waking during the night', 'waking too early', and 'feeling unrested during the day'. OSA was classified as a combination of a positive response to a physician-diagnosed condition, in addition to a high frequency of self-reported nocturnal 'snoring', 'snorting/stopping breathing' and 'feeling overly sleepy during the day'. Comorbid insomnia-OSA was further assessed by combining a positive response to either insomnia (all), or sleep apnoea (all), as classified above. Depressive symptomology was assessed by the Patient Health Questionnaire-9 (PHQ-9), with scores of >9 used to indicate depression. Odds ratios (ORs) and 95% confidence intervals (CIs) for sleep disorders and depression were attained from logistic regression modelling adjusted for sex, age, poverty level, smoking status and body mass index (BMI). RESULTS: Those who reported insomnia, OSA or comorbid insomnia-OSA symptoms reported higher rates of depression (33.6%, 22.2%, 27.1%, respectively), and consistently reported poorer physical health outcomes than those who did not report sleep disorders. After adjusting for sex, age, poverty level, smoking status and BMI (kg/m(2)), insomnia (OR 6.57, 95% CI 3.89 11.11), OSA (OR 5.14, 95% CI 3.14-8.41) and comorbid insomnia-OSA (OR 6.67, 95% CI 4.44-10.00) were associated with an increased likelihood of reporting depression. CONCLUSIONS: Insomnia, OSA and comorbid insomnia-OSA are associated with significant depressive symptomology among this large population-based sample of adults. PMID- 25128226 TI - Progress towards parity: improving the physical health of long-term psychiatric inpatients. PMID- 25128227 TI - Identification of putative pathogenic microRNA and its downstream targets in anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. AB - Anaplastic large cell lymphomas (ALCL) are tumors of T/null-cell lineage characterized by uniform CD30 expression. The 2008 World Health Organization classification subdivided ALCLs into 2 groups: anaplastic lymphoma kinase (ALK) positive (established entity) and ALK-negative (proposed new entity) ALCL. The genetic basis for the pathogenesis of newly categorized ALK- ALCL is poorly understood. In this study, we used microRNA microarray analysis to identify differentially expressed microRNAs in ALK+ and ALK- ALCL. ALK- ALCL showed significantly higher expression of miR-155 (0.888 +/- 0.228) compared with ALK+ ALCL (0.0565 +/- 0.009) on microarray and by quantitative real-time polymerase chain reaction in ALK- ALCL compared with ALK+ ALCL (P < .05) with a strong correlation between the 2 platforms (R = 0.9, P < .0003). A novel in situ hybridization method allows direct visualization of expression patterns and relative quantitation of miR-155 (mean score, 2.3 versus 1.3; P = .01) for the first time in tissue sections of ALCL. Among computationally predicted targets of miR-155, we identified ZNF652 (r = -0.57, P = .05), BACH1 (r = 0.88, P = .02), RBAK (r = 0.81, P = .05), TRIM32 (r = 0.92, P = .01), E2F2 (r = 0.81, P = .05), and TP53INP1 (r = -0.31, P = .03) as genes whose expression by quantitative real time polymerase chain reaction correlated significantly with the level of miR-155 in ALCL tumor tissue. PMID- 25128229 TI - Diagnosis of major cancer resection specimens with virtual slides: impact of a novel digital pathology workstation. AB - Digital pathology promises a number of benefits in efficiency in surgical pathology, yet the longer time required to review a virtual slide than a glass slide currently represents a significant barrier to the routine use of digital pathology. We aimed to create a novel workstation that enables pathologists to view a case as quickly as on the conventional microscope. The Leeds Virtual Microscope (LVM) was evaluated using a mixed factorial experimental design. Twelve consultant pathologists took part, each viewing one long cancer case (12 25 slides) on the LVM and one on a conventional microscope. Total time taken and diagnostic confidence were similar for the microscope and LVM, as was the mean slide viewing time. On the LVM, participants spent a significantly greater proportion of the total task time viewing slides and revisited slides more often. The unique design of the LVM, enabling real-time rendering of virtual slides while providing users with a quick and intuitive way to navigate within and between slides, makes use of digital pathology in routine practice a realistic possibility. With further practice with the system, diagnostic efficiency on the LVM is likely to increase yet more. PMID- 25128228 TI - Prostate cancer with Paneth cell-like neuroendocrine differentiation has recognizable histomorphology and harbors AURKA gene amplification. AB - Aurora kinase A (AURKA) gene amplification has been documented in 67% of hormone naive prostate cancer cases that progress to a highly aggressive variant of castrate-resistant disease, clinically referred to as "neuroendocrine" prostate cancer, "small cell" prostate carcinoma, or "anaplastic" prostate cancer. Therefore, AURKA amplification is a potential prognostic biomarker that may help to identify patients with prostate cancer who are at high risk for developing castrate-resistant disease with clinical features of small cell carcinoma. Furthermore, AURKA inhibitors are currently being tested in clinical trials. In a previous study, we found AURKA amplification in 6 cases of prostate cancer with Paneth cell-like cells. This morphologic pattern has been suggested to represent low-grade neuroendocrine differentiation (NED) with generally favorable prognosis. We sought to investigate the frequency of AURKA amplification and the histologic characteristics of prostate cancer with Paneth cell-like NED. Twenty five cases from 172 prostatectomies were evaluated for the presence of 18 morphologic features and AURKA amplification. Most prostate cancers with Paneth cell-like NED had macronucleoli (92%), basophilic appearance (88%), perineural invasion (72%), and nuclear stratification (76%). The frequency of AURKA amplification was 45%, present throughout the examined tumor nodule including areas without Paneth cell-like cells. When histologically similar cases with and without AURKA amplification were compared, this gene alteration was associated with larger extent of Paneth cell-like NED identified at magnification *20 (P = .015), higher percentage of Paneth cell-like NED throughout the tumor nodule (P = .033), ductal features (P = .02), and higher overall Gleason grade (P = .039). AURKA amplification was not associated with age, serum prostate specific antigen, or tumor stage. The high frequency of AURKA amplification (45%) in localized prostate cancer with Paneth cell-like NED and its potential prognostic significance warrant further investigation. PMID- 25128230 TI - How neuronal computations depend on network state: another piece in the puzzle. PMID- 25128231 TI - Dissecting mechanisms behind force control in humans by a mixture of experimentation, mathematical analysis and computer simulations of neuronal models. PMID- 25128232 TI - Calcium channels for endocytosis. PMID- 25128235 TI - A study on stability and medical implications for a complex delay model for CML with cell competition and treatment. AB - We study a mathematical model describing the dynamics of leukemic and normal cell populations (stem-like and differentiated) in chronic myeloid leukemia (CML). This model is a system of four delay differential equations incorporating three types of cell division. The competition between normal and leukemic stem cell populations for the common microenvironment is taken into consideration. The stability of one steady state is investigated. The results are discussed via their medical interpretation. PMID- 25128236 TI - Economic principles in communication: an experimental study. AB - This paper experimentally investigates how economic principles affect communication. In a simple sender-receiver game with common interests over payoffs, the sender can send a signal without a pre-given meaning in an infrequent or frequent state of the world. When the signal is costly, several theories (focal point theory, the intuitive criterion, evolutionary game theory) predict an efficient separating equilibrium, where the signal is sent in the infrequent state of the world (also referred to as Horn's rule). To analyze whether Horn's rule applies, and if so, which theory best explains it, we develop and test variants of the sender-receiver game where the theories generate discriminatory hypotheses. In costly signaling variants, our participants follow Horn's rule most of the time, in a manner that is best explained by focal point theory. In costless signaling variants, evolutionary game theory best explains our results. Here participants coordinate significantly more (less) often on a separating equilibrium where the signal is sent in the frequent state if they are primed to associate the absence of a signal with the infrequent (frequent) state of the world. We also find indications that a similar priming effect applies to costly signals. Thus, while the frequency with which participants follow Horn's rule in costly signaling variants is best explained by Horn's rule, the priming effect shows that some of our participants' behavior is best explained by evolutionary game theory even when signals are costly. PMID- 25128234 TI - Fluoroscopic guidance for placing a double lumen endotracheal tube in adults. AB - OBJECTIVE: The aim of this study was to assess the right placement of the double lumen endotracheal tube with fluoroscopic guidance, which is used in first intention prior to the fiberscope in our institution. METHODS: This was a prospective observational study. The study was conducted in vascular and thoracic operating rooms. We enrolled 205 patients scheduled for thoracic surgery, with ASA physical statuses of I (n = 37), II (n = 84), III (n = 80), and IV (n = 4). Thoracic procedures were biopsy (n = 20), wedge (n = 34), culminectomy (n = 6), lobectomy (n = 82), pneumonectomy (n = 4), sympathectomy (n = 9), symphysis (n = 47), and thymectomy (n = 3). The intubation with a double lumen tube was performed with the help of a laryngoscope. Tracheal and bronchial balloons were inflated and auscultation was performed after right and left exclusions. One shot was performed to locate the position of the bronchial tube and the hook. Fluoroscopic guidance was used to relocate the tube in case of a wrong position. When the fluoroscopic guidance failed to position the tube, a fiberscope was used. Perioperative collapse of the lung was assessed by the surgeon during the surgery. RESULTS: Correct fluoroscopic image was obtained after the first attempt in 58.5% of patients therefore a misplaced position was encountered in 41.5%. The fluoroscopic guidance allowed an exact repositioning in 99.5% of cases, and the mean duration of the procedure was 8 minutes. A fiberscope was required to move the hook for one patient. We did not notice a moving of the double lumen endotracheal tube during the surgery. The surgeon satisfaction was 100%. CONCLUSION: The fluoroscopy evidenced the right position of the double lumen tube and allowed a right repositioning in 99.5% of patients with a very simple implementation. PMID- 25128237 TI - Wing motion transformation to evaluate aerodynamic coupling in flapping wing flight. AB - Whether the remarkable flight performance of insects is because the animals leverage inherent physics at this scale or because they employ specialized neural feedback mechanisms is an active research question. In this study, an empirically derived aerodynamics model is used with a transformation involving a delay and a rotation to identify a class of kinematics that provide favorable roll-yaw coupling. The transformation is also used to transform both synthetic and experimentally measured wing motions onto the manifold representing proverse yaw and to quantify the degree to which freely flying insects make use of passive aerodynamic mechanisms to provide proverse roll-yaw turn coordination. The transformation indicates that recorded insect kinematics do act to provide proverse yaw for a variety of maneuvers. This finding suggests that passive aerodynamic mechanisms can act to reduce the neural feedback demands of an insect's flight control strategy. PMID- 25128238 TI - Effect of treatment on the global dynamics of delayed pathological angiogenesis models. AB - For three different types of angiogenesis models with variable delays, we consider either continuous or impulse therapy that eradicates tumor cells and suppresses angiogenesis. For the cancer-free solution, explicit conditions of global stability for the continuous and impulsive systems are obtained, together with delay-dependent estimates for the rates of decay for the tumor volume and pathological angiogenesis. PMID- 25128241 TI - Antiphospholipid syndrome and acute myocardial infarction: treatment with thrombectomy and abciximab. AB - Antiphospholipid syndrome (APS) is an autoimmune coagulation disorder that manifests clinically as venous and arterial thrombosis, and may affect any tissue or organ. Coronary artery involvement, however, is very rare. Case reports in the literature describing patients with coronary acute syndrome and APS treated with coronary angioplasty show conflicting results. We report an adult male patient with APS who presented with an acute myocardial infarction. Given the high risk of thrombosis in these patients, he was treated percutaneously with thrombectomy and abciximab. We review the few cases of coronary angioplasty in patients with APS reported to date. To our knowledge, this is the first case in which acute myocardial infarction due to thrombotic coronary occlusion was treated with thrombectomy and abciximab without stenting the artery. PMID- 25128247 TI - [Clinical analysis and surgical results of 58 paranasal sinus mucoceles]. AB - INTRODUCTION: Mucoceles are slow-growing, benign lesions found in the paranasal sinuses that are locally destructive, causing bony resorption an displacement of adjacent structures. We present our experience in the surgical treatment of these lesions. METHODS: This was a retrospective review of 58 paranasal sinus mucoceles in 54 patients between 1989 and 2012. We describe patient age and sex, mucocele location, clinical features, surgical approaches employed, recurrence and complications. RESULTS: The mean age of patients in this series was 59 years; there were 31 males (57%) and 23 females (43%). Thirty-two cases (55%) were located in the frontal or ethmoid-frontal system, 8 (14%) in the ethmoid sinus, 14 (24%) in the maxillary sinus and 4 (7%) in sphenoid sinus. Predisposing factors were present in 55% of the patients and 45% cases were primary. Endoscopic treatment was given to 71% of mucocele patients, while 29% were treated with external or combined approaches. Recurrence appeared in 4 patients (7%), 2 in the endoscopic surgery group and 2 in the external surgery group. CONCLUSIONS: The procedure of choice for management of paranasal sinus mucoceles is endoscopic drainage. It is a safe approach that gives good results. PMID- 25128240 TI - Analysis of natural and induced variation in tomato glandular trichome flavonoids identifies a gene not present in the reference genome. AB - Flavonoids are ubiquitous plant aromatic specialized metabolites found in a variety of cell types and organs. Methylated flavonoids are detected in secreting glandular trichomes of various Solanum species, including the cultivated tomato (Solanum lycopersicum). Inspection of the sequenced S. lycopersicum Heinz 1706 reference genome revealed a close homolog of Solanum habrochaites MOMT1 3'/5' myricetin O-methyltransferase gene, but this gene (Solyc06g083450) is missing the first exon, raising the question of whether cultivated tomato has a distinct 3' or 3'/5' O-methyltransferase. A combination of mining genome and cDNA sequences from wild tomato species and S. lycopersicum cultivar M82 led to the identification of Sl-MOMT4 as a 3' O-methyltransferase. In parallel, three independent ethyl methanesulfonate mutants in the S. lycopersicum cultivar M82 background were identified as having reduced amounts of di- and trimethylated myricetins and increased monomethylated myricetin. Consistent with the hypothesis that Sl-MOMT4 is a 3' O-methyltransferase gene, all three myricetin methylation defective mutants were found to have defects in MOMT4 sequence, transcript accumulation, or 3'-O-methyltransferase enzyme activity. Surprisingly, no MOMT4 sequence is found in the Heinz 1706 reference genome sequence, and this cultivar accumulates 3-methyl myricetin and is deficient in 3'-methyl myricetins, demonstrating variation in this gene among cultivated tomato varieties. PMID- 25128239 TI - Role of transcription factor yin yang 1 in manganese-induced reduction of astrocytic glutamate transporters: Putative mechanism for manganese-induced neurotoxicity. AB - Astrocytes are the most abundant non-neuronal glial cells in the brain. Once relegated to a mere supportive role for neurons, contemporary dogmas ascribe multiple active roles for these cells in central nervous system (CNS) function, including maintenance of optimal glutamate levels in synapses. Regulation of glutamate levels in the synaptic cleft is crucial for preventing excitotoxic neuronal injury. Glutamate levels are regulated predominantly by two astrocytic glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST). Indeed, the dysregulation of these transporters has been linked to several neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD), as well as manganism, which is caused by overexposure to the trace metal, manganese (Mn). Although Mn is an essential trace element, its excessive accumulation in the brain as a result of chronic occupational or environmental exposures induces a neurological disorder referred to as manganism, which shares common pathological features with Parkinsonism. Mn decreases the expression and function of both GLAST and GLT-1. Astrocytes are commonly targeted by Mn, and thus reduction in astrocytic glutamate transporter function represents a critical mechanism of Mn induced neurotoxicity. In this review, we will discuss the role of astrocytic glutamate transporters in neurodegenerative diseases and Mn-induced neurotoxicity. PMID- 25128248 TI - Relative contributions of negative symptoms, insight, and coping strategies to quality of life in stable schizophrenia. AB - The purpose of this cross-sectional study was to examine the relative contributions of negative symptomatology, insight, and coping to quality of life (QOL) in a sample of 92 consecutive outpatients with stable schizophrenia referring to the Department of Neuroscience, Psychiatric Section, University of Turin, Struttura Semplice di Coordinamento a Valenza Dipartimentale (SSCVD), Department of Mental Health ASL TO1, Molinette, Italy, in the period between July 2009 and July 2011. In order to assess the specific effect of negative symptoms on QOL and the possible mediating role of insight and coping, two mediation hypotheses were tested, using multiple regression analyses specified by Baron and Kenny (1986). Our findings suggest that (a) higher negative symptoms predict a worse Quality of Life Scale (QLS) intrapsychic foundations (IF) subscale score; (b) attribution of symptoms and coping-social diversion have a direct and positive association with QLS-IF; (c) patients high in negative symptoms are less likely to use attribution of symptoms and coping-social diversion; and (d) attribution of symptoms and coping-social diversion act as partial mediators in the negative symptoms-QOL relationship. The prediction model accounts for 45.3% of the variance of the QLS-IF subscale score in our sample. In conclusion, our results suggest that insight and coping-social diversion substantially contribute to QOL in patients with higher negative symptoms. These factors are potentially modifiable from specific therapeutic interventions, which can produce considerable improvements in the QOL of this population. PMID- 25128249 TI - An investigation into reasoning biases, mood and cognitive state, and subclinical delusional ideation. AB - Following research on reasoning and the continuum of delusional ideation, the present study attempted to investigate the impact of different experimentally induced states (stress, paranoia, and neutral) on the jumping-to-conclusions reasoning bias in individuals with varying levels of subclinical delusional ideation (SDI). Participants (N=117) completed a measure of subclinical delusional ideation (the Peters et al. Delusions Inventory or PDI; Peters et al., 1999); and were randomly assigned to receive one of two experimental inductions (stress or paranoia), or no experimental induction; their performance on two probabilistic reasoning tasks--one easy and one challenging--was assessed. Although no differences were found between individuals with high vs. low subclinical delusional ideation in the no induction condition or following the paranoia induction, in the stress-induction condition, individuals with high levels of subclinical delusional ideation were significantly less likely to jump to conclusions on the easy reasoning task. No significant effects emerged on the more challenging task. Assessment of post-test paranoid thinking indicated our paranoia induction did not have its intended effect. Importantly, because there was no pre-test of anxiety, paranoid thinking, or reasoning to determine if they shifted after the inductions, results need to be interpreted with caution. PMID- 25128250 TI - Post-traumatic psychological changes among survivors of the Lushan earthquake living in the most affected areas. AB - The primary objective of our study was to investigate both the negative and positive psychological changes following the Lushan earthquake, and to explore the factors associated with psychological changes. Multi-stage random sampling was used to select respondents from Lushan County, Sichuan Province, China. A simplified Chinese version of the short form of Changes in Outlook Questionnaire (CiOQ-S) was used to assess psychological changes in earthquake survivors. Descriptive statistics, t-tests, ANOVA and stepwise linear regression analysis were used for data analysis. A total of 4972 respondents were investigated in the cross-sectional study. The mean scores of the positive and negative psychological changes were 26.61 and 8.12, respectively. The factors associated with positive psychological changes included ethnic minority, high level of education, high household income, not injured in the earthquake, not trapped during the earthquake, and having experienced the Wenchuan earthquake. The factors associated with negative psychological changes included female gender, ethnic minority, low household income, history of diseases, injured during the earthquake, and trapped during the earthquake. The current analysis helps expand our knowledge of the negative and positive psychological changes that may occur following an earthquake experience. PMID- 25128251 TI - Differences in the developmental patterns of depression with and without additional somatic symptoms. AB - Depression accompanied by somatic symptoms ("somatic" depression) has been found to differ from depression without the additional symptoms ("pure" depression) in their gender ratio, their association with measures of perceived gender inequality taken from both respondents and their parents, and in their response to pharmacological treatment. Further evidence of the distinction between the two syndromes might come from differential patterns of development. Data on the annual incidence of new cases of depression exhibited by a representative sample of respondents aged 12-19 came from the National household survey on drug use and health. Between early adolescence (ages 12-14) and late adolescence (ages 15-19), female respondents exhibited a much larger increase in somatic depression than in pure depression. Males did not exhibit the same pattern. These results further support the hypothesis that somatic and pure depressions are two distinct disorders. PMID- 25128252 TI - Still in the closet: the invisible minority in medical education. AB - BACKGROUND: To investigate the relationship between sexual orientation and gender identity in regard to levels of depression; levels of perceived social support; comfort with disclosure of orientation; and the lesbian, gay, bisexual, and transgender (LGBT) campus climate. METHODS: E-mail invitations to participate in the current cross-sectional questionnaire-based study were sent to all thirty US osteopathic medical schools in August 2012; six schools responded and disseminated the survey to their students. Participating students completed an anonymous web-based survey, and informed consent was obtained when they accessed the survey. The survey was designed specifically for the current study but contained scales used with permission from previously published research. Analysis procedures included nonparametric tests, one-way analysis of variance and Pearson's correlations. RESULTS: Of the 4112 students invited to participate in the survey, 1334 (32.4%) completed it. Approximately 85% of respondents self identified as heterosexual only. No respondents identified as transgender. In general, LGB students indicated higher levels of depression (P < .001), slightly lower levels of perceived social support (P < .001), and more discomfort with disclosure of sexual orientation (P < .001). A majority of students rated their campus climate as noninclusive. CONCLUSIONS: Results of the current study indicated a relationship between sexual orientation and depression, perceived social support, comfort with disclosure of orientation, and the LGBT campus climate in osteopathic medical students. In the future, osteopathic medical schools should consider closely examining their campus culture in order to create a more positive and inclusive environment for all its students. PMID- 25128253 TI - Reply: To PMID 24561105. PMID- 25128254 TI - Intraoperative hyperkalemia induced by administration of trimethoprim sulfamethoxazole in a patient receiving angiotensin receptor blockers. PMID- 25128255 TI - Cluster-based computational methods for mass univariate analyses of event-related brain potentials/fields: A simulation study. AB - BACKGROUND: In recent years, analyses of event related potentials/fields have moved from the selection of a few components and peaks to a mass-univariate approach in which the whole data space is analyzed. Such extensive testing increases the number of false positives and correction for multiple comparisons is needed. METHOD: Here we review all cluster-based correction for multiple comparison methods (cluster-height, cluster-size, cluster-mass, and threshold free cluster enhancement - TFCE), in conjunction with two computational approaches (permutation and bootstrap). RESULTS: Data driven Monte-Carlo simulations comparing two conditions within subjects (two sample Student's t test) showed that, on average, all cluster-based methods using permutation or bootstrap alike control well the family-wise error rate (FWER), with a few caveats. CONCLUSIONS: (i) A minimum of 800 iterations are necessary to obtain stable results; (ii) below 50 trials, bootstrap methods are too conservative; (iii) for low critical family-wise error rates (e.g. p=1%), permutations can be too liberal; (iv) TFCE controls best the type 1 error rate with an attenuated extent parameter (i.e. power<1). PMID- 25128257 TI - Digital filter design for electrophysiological data--a practical approach. AB - BACKGROUND: Filtering is a ubiquitous step in the preprocessing of electroencephalographic (EEG) and magnetoencephalographic (MEG) data. Besides the intended effect of the attenuation of signal components considered as noise, filtering can also result in various unintended adverse filter effects (distortions such as smoothing) and filter artifacts. METHOD: We give some practical guidelines for the evaluation of filter responses (impulse and frequency response) and the selection of filter types (high-pass/low-pass/band pass/band-stop; finite/infinite impulse response, FIR/IIR) and filter parameters (cutoff frequencies, filter order and roll-off, ripple, delay and causality) to optimize signal-to-noise ratio and avoid or reduce signal distortions for selected electrophysiological applications. RESULTS: Various filter implementations in common electrophysiology software packages are introduced and discussed. Resulting filter responses are compared and evaluated. CONCLUSION: We present strategies for recognizing common adverse filter effects and filter artifacts and demonstrate them in practical examples. Best practices and recommendations for the selection and reporting of filter parameters, limitations, and alternatives to filtering are discussed. PMID- 25128258 TI - Radical resection of a Shamblin type III carotid body tumour without cerebro neurological deficit: Improved technique with preoperative embolization and carotid stenting. AB - The surgical resection of a large unfavourable Shamblin type III carotid body tumour (CBT) can be very challenging technically, with many potential significant complications. Preoperative embolization aids in shrinking the lesion, reducing intraoperative blood loss, and improving visualization of the surgical field. Preoperative internal carotid artery (ICA) stenting aids in reinforcing the arterial wall, thereby providing a better dissection plane. A woman presented to our institution with a large right-sided CBT. Failure of the preoperative temporary balloon occlusion (TBO) test emphasized the importance of intraoperative preservation of the ipsilateral ICA. A combination of both preoperative embolization and carotid stenting allowed a less hazardous radical resection of the CBT. An almost bloodless surgical field permitted meticulous dissection, hence reducing the risk of intraoperative vascular and nerve injury. Embolization and carotid stenting prior to surgical resection should be considered in cases with bilateral CBT or a skull base orientated high CBT, and for those with intracranial extension and patients who have failed the TBO test. PMID- 25128256 TI - Non-causal spike filtering improves decoding of movement intention for intracortical BCIs. AB - BACKGROUND: Multiple types of neural signals are available for controlling assistive devices through brain-computer interfaces (BCIs). Intracortically recorded spiking neural signals are attractive for BCIs because they can in principle provide greater fidelity of encoded information compared to electrocorticographic (ECoG) signals and electroencephalograms (EEGs). Recent reports show that the information content of these spiking neural signals can be reliably extracted simply by causally band-pass filtering the recorded extracellular voltage signals and then applying a spike detection threshold, without relying on "sorting" action potentials. NEW METHOD: We show that replacing the causal filter with an equivalent non-causal filter increases the information content extracted from the extracellular spiking signal and improves decoding of intended movement direction. This method can be used for real-time BCI applications by using a 4ms lag between recording and filtering neural signals. RESULTS: Across 18 sessions from two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial, we found that threshold crossing events extracted using this non-causal filtering method were significantly more informative of each participant's intended cursor kinematics compared to threshold crossing events derived from causally filtered signals. This new method decreased the mean angular error between the intended and decoded cursor direction by 9.7 degrees for participant S3, who was implanted 5.4 years prior to this study, and by 3.5 degrees for participant T2, who was implanted 3 months prior to this study. CONCLUSIONS: Non-causally filtering neural signals prior to extracting threshold crossing events may be a simple yet effective way to condition intracortically recorded neural activity for direct control of external devices through BCIs. PMID- 25128259 TI - Wound ballistics of firearm-related injuries--part 1: missile characteristics and mechanisms of soft tissue wounding. AB - Firearm-related injuries are caused by a wide variety of weapons and projectiles. The kinetic energy of the penetrating projectile defines its ability to disrupt and displace tissue, whereas the actual tissue damage is determined by the mode of energy release during the projectile-tissue interaction and the particular characteristics of the tissues and organs involved. Certain projectile factors, namely shape, construction, and stability, greatly influence the rate of energy transfer to the tissues along the wound track. Two zones of tissue damage can be identified, the permanent cavity created by the passage of the bullet and a potential area of contused tissue surrounding it, produced mainly by temporary cavitation which is a manifestation of effective high-energy transfer to tissue. Due to the complex nature of these injuries, wound assessment and the type and extent of treatment required should be based on an understanding of the various mechanisms contributing to tissue damage. PMID- 25128260 TI - Auto-fluorescence of the bone and its use for delineation of bone necrosis. AB - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging complication of long-term bisphosphonate treatment. Currently, the drawback in the surgical management of BRONJ is the difficulty distinguishing between viable and necrotic bone. Intraoperative bone fluorescence induced by tetracyclines has been shown to be a valuable aid to overcome this problem. In this technical note we report the finding that viable bone is auto-fluorescent using the VELscope Vx fluorescence lamp. Necrotic bone shows an altered fluorescence pattern (pale or no fluorescence). Thus it is suggested that auto-fluorescence of bone might be of similar use during the surgical therapy of BRONJ. PMID- 25128261 TI - Complications associated with inferior alveolar nerve repositioning for dental implant placement: a systematic review. AB - Inferior alveolar nerve (IAN) repositioning has been used widely in recent years as an alternative approach for dental implant placement in the atrophic posterior mandible. The aim of this study was to answer the question: What are the complications associated with IAN repositioning? A systematic literature review performed in accordance with the PRISMA statement, using the PubMed (MEDLINE), Cochrane Library, and Scopus databases, identified a total of 116 articles related to this technique. Of those articles, 24 were included in the final review. Lateralization was the chosen technique in seven studies, transposition in 15 studies, and two studies reported both techniques. The longest follow-up period was 49.1 months and the shortest 6 months. Of the patients who underwent lateralization, 95.9% initially showed a neurosensory disturbance, and the condition remained at the end of the study for 3.4% of those patients. With regard to the patients who underwent transposition, neurosensory alterations were observed in 58.9% of patients initially, and the condition remained for 22.1% of those affected at the end of the study. Only one study found no neurosensory disturbance at any time. More data consolidation is necessary to determine scientifically if, which, and when the IAN repositioning technique can be recommended. PMID- 25128262 TI - Comparison of related complications: sentinel node biopsy versus elective neck dissection. AB - Sentinel node biopsy (SNB) is considered a feasible neck staging tool in early oral squamous cell carcinoma. The aim of this study was to compare postoperative morbidity in patients who had undergone SNB and elective neck dissection (END). Seventy-three consecutive patients were included between the years 2005 and 2009. The patients were divided into two groups according to neck management: SNB and END groups. Kaplan-Meier survival analysis was used to compare disease-free survival (DFS) and overall survival (OS) between the groups. Shoulder function, length of the surgical scar, and the degree of cervical lymphoedema were assessed. Neck haematoma and the presence of oro-cervical communication were also analyzed. Thirty-two patients underwent SNB and 41 underwent an END (levels I III). Seven regional recurrences were recorded in the END group. Three neck recurrences occurred in the SNB group. No significant differences were found in DFS or OS between the groups. There were statistically significant differences between the groups in shoulder function and average scar length. However, differences in degree of lymphoedema were not statistically significant. Neck hematomas and oro-cervical communications occurred only in the END group. From this study, it can be concluded that SNB presents less postoperative morbidity than END. PMID- 25128263 TI - Wound ballistics of firearm-related injuries--part 2: mechanisms of skeletal injury and characteristics of maxillofacial ballistic trauma. AB - Maxillofacial firearm-related injuries vary in extent and severity because of the characteristics and behaviour of the projectile(s), and the complexity of the anatomical structures involved, whereas the degree of tissue disruption is also affected by the distance of the shot. In low-energy injuries there is limited damage to the underlying skeleton, which usually dominates the clinical picture, dictating a more straightforward therapeutic approach. High-energy injuries are associated with extensive hard and soft tissue disruption, and are characterized by a surrounding zone of damaged tissue that is prone to progressive necrosis as a result of compromised blood supply and wound sepsis. Current treatment protocols for these injuries emphasize the importance of serial debridement for effective wound control while favouring early definitive reconstruction. PMID- 25128264 TI - MicroRNAs: Small molecules with big roles in neurodevelopment and diseases. AB - MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that play important roles in the development and functions of the brain. Extensive studies have revealed critical roles for miRNAs in brain development and function. Dysregulation or altered expression of miRNAs is associated with abnormal brain development and pathogenesis of neurodevelopmental diseases. This review serves to highlight the versatile roles of these small RNA molecules in normal brain development and their association with neurodevelopmental disorders, in particular, two closely related neuropsychiatric disorders of neurodevelopmental origin, schizophrenia and bipolar disorder. PMID- 25128266 TI - Poorer glycaemic control in type 1 diabetes is associated with reduced self management and poorer perceived health: a cross-sectional study. AB - AIMS: Many people with type 1 diabetes do not achieve optimal treatment targets despite high patient and professional input. To investigate the reasons underlying suboptimal control we have studied clinical characteristics and self management behaviours in adults with type 1 diabetes attending a large treatment centre. METHODS: A questionnaire-based enquiry into self-care behaviours of 380 patients with type 1 diabetes (mean age: 48 (+/-15) years and mean duration of diabetes: 26 (+/-15) years), linked with validated measures of impact of treatment on perceived health and hypoglycaemia recognition (Insulin Treatment Satisfaction Questionnaire; and EuroQoL EQ-5D, Gold score) and retrospective case note review of biomedical parameters. The data were analysed using chi-square test, ANOVA, ANCOVA and post-hoc procedures (Tukey's-b) in SPSS-version 18. The minimum significance level was accepted as 0.05. RESULTS: Sixty three percent of participants used multiple daily injections; 36% continuous subcutaneous insulin infusion. Mean HbA1c was 7.7% (+/-1.2) [61+/--10mmol/mol]; 30% had impaired hypoglycaemia awareness (IHA). Factors significantly related to poor glycaemic control with IHA were longer duration of diabetes (p=0.01); less frequent glucose self-monitoring (p=0.05); and low level of patient-set glucose targets (p<0.001). Patients with IHA and poorer control had significantly lower insulin treatment satisfaction (p<0.001); and perceived health (p<0.001). CONCLUSIONS: Suboptimal biomedical outcomes in adults with type 1 diabetes attending a specialist intensified insulin therapy clinic are associated with longer duration of diabetes, fewer self-management behaviours and a trend towards poorer perceived health. These data suggest a need for greater emphasis on integration of psychological and self-management support with intensive medical management of type 1 diabetes. PMID- 25128267 TI - Focusing on potential sources of glucose fluctuations in type 1 and type 2 diabetes: which kind of patient, what kind of glycemic variability and which confounding factors? PMID- 25128265 TI - A comparative morphological, electrophysiological and functional analysis of axon regeneration through peripheral nerve autografts genetically modified to overexpress BDNF, CNTF, GDNF, NGF, NT3 or VEGF. AB - The clinical outcome of microsurgical repair of an injured peripheral nerve with an autograft is suboptimal. A key question addressed here is: can axon regeneration through an autograft be further improved? In this article the impact of six neurotrophic factors (BDNF, CNTF, GDNF, NGF, NT3 or VEGF) on axon regeneration was compared after delivery to a 1cm long nerve autograft by gene therapy. To distinguish between early and late effects, regeneration was assessed at 2 and 20weeks post-surgery by histological, electrophysiological and functional analysis. BDNF, GDNF and NGF exhibited a spectrum of effects, including early stimulatory effects on axons entering the autograft and excessive axon growth and Schwann cell proliferation at 20weeks post-surgery. Persistent expression of these factors in autografts interfered with target cell reinnervation and functional recovery in a modality specific way. Autografts overexpressing VEGF displayed hypervascularization, while grafts transduced with CNTF and NT3 were indistinguishable from control grafts. These three factors did not have detectable pro-regenerative effects. In conclusion, autograft-based repair combined with gene therapy for three of the six growth factors investigated (BDNF, GDNF, NGF) showed considerable promise since these factors enhanced modality specific axon outgrowth in autografts. The remarkable and selective effects of BDNF, GDNF and NGF on motor or sensory regeneration will be exploited in future experiments that aim to carefully regulate their temporal and spatial expression since this has the potential to overcome the adverse effects on long-distance regeneration observed after uncontrolled delivery. PMID- 25128268 TI - Treatment costs of psoriasis in a tertiary-level clinic. AB - BACKGROUND: The costs of psoriasis to a tertiary-level clinic vary considerably depending on the country of study and methods used. Hospitalisation and phototherapy have been significant cost components. This study was performed to estimate the distribution and relative magnitude of the costs of psoriasis to a tertiary-level clinic. METHODS: Based on 233 patients, outpatient and phototherapy visits and the days hospitalised were collected from the treatment provider's records. The visit costs represented true costs, used to charge the final payers. Patients were analysed according to their treatment modalities. RESULTS: On average, hospitalised patients (3.4%) had 31-fold higher total costs than non-hospitalised patients (p < 0.0001). The costs of hospitalisations formed 45% of all the treatment costs to the entire study population. Phototherapy accumulated 19% of the overall treatment costs. Patients receiving biological drugs or both phototherapy and traditional systemic therapy had the highest costs of treatment. CONCLUSIONS: The current study indicates that a small percentage of all psoriasis patients generate a large proportion of the overall costs to a tertiary-level hospital. Treatment modality has a significant effect on the costs to a tertiary-level hospital. PMID- 25128269 TI - Airbrushed composite polymer Zr-ACP nanofiber scaffolds with improved cell penetration for bone tissue regeneration. AB - Electrospun polymer nanofibers have multiple applications in the tissue engineering field despite limited cell penetration within the scaffolds and slow synthesis rates. Airbrushing, a proposed alternative to traditional electrospinning, is a technique capable of synthesizing open structure nanofiber scaffolds at high rates. In this study, three biocompatible polymers-poly-D,L lactic acid (P-DL-LA), polycaprolactone (PCL), and poly(methyl methacrylate) (PMMA), were airbrushed to form networks for bone tissue regeneration. All three polymers were loaded with up to 20% (w/w) zirconium-modified amorphous calcium phosphate (Zr-ACP). A simple one-step mix and straightforward material deposition yielded open structure networks with well-distributed Zr-ACP. Cell penetration within the airbrushed scaffolds was found to be more than twice the cell penetration within conventional electrospun networks. The airbrushed polymer network supported cell growth and differentiation. Cells grown on the Zr-ACP in P DL-LA fibers exhibited improved levels of osteocalcin protein with an increase in the Zr-ACP content by day 16. This airbrushing method promises to be a viable and attractive alternative to currently used electrospinning techniques in the formation of composite 3D nanofiber scaffolds for tissue engineering applications. PMID- 25128270 TI - Timing of enteral nutrition in acute pancreatitis: meta-analysis of individuals using a single-arm of randomised trials. AB - INTRODUCTION: In acute pancreatitis, enteral nutrition (EN) reduces the rate of complications, such as infected pancreatic necrosis, organ failure, and mortality, as compared to parenteral nutrition (PN). Starting EN within 24 h of admission might further reduce complications. METHODS: A literature search for trials of EN in acute pancreatitis was performed. Authors of eligible trials were requested to provide the data of all patients in the EN-arm of their trials. A meta-analysis of individual patient data was performed. The cohort of patients with EN was divided into patients receiving EN within 24 h or after 24 h of admission. Multivariable logistic regression, adjusting for predicted disease severity and trial, was used to study the effect of timing of EN on a composite endpoint of infected pancreatic necrosis, organ failure, or mortality. RESULTS: Observational data from 165 individuals from 8 randomised trials were obtained; 100 patients with EN within 24 h and 65 patients with EN after 24 h of admission. In the multivariable model, EN started within 24 h of admission compared to EN started after 24 h of admission, reduced the composite endpoint from 45% to 19% (adjusted odds ratio [OR] of 0.44; 95% confidence interval [CI] 0.20-0.96). Within the composite endpoint, organ failure was reduced from 42% to 16% (adjusted OR 0.42; 95% CI 0.19-0.94). CONCLUSIONS: In this meta-analysis of observational data from individuals with acute pancreatitis, starting EN within 24 h after hospital admission, compared with after 24 h, was associated with a reduction in complications. PMID- 25128272 TI - Antenatal corticosteroids 40 years on: we can do better. PMID- 25128271 TI - Use of antenatal corticosteroids and tocolytic drugs in preterm births in 29 countries: an analysis of the WHO Multicountry Survey on Maternal and Newborn Health. AB - BACKGROUND: Despite the global burden of morbidity and mortality associated with preterm birth, little evidence is available for use of antenatal corticosteroids and tocolytic drugs in preterm births in low-income and middle-income countries. We analysed data from the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS) to assess coverage for these interventions in preterm deliveries. METHODS: WHOMCS is a facility-based, cross-sectional survey database of birth outcomes in 359 facilities in 29 countries, with data collected prospectively from May 1, 2010, to Dec 31, 2011. For this analysis, we included deliveries after 22 weeks' gestation and we excluded births that occurred outside a facility or quicker than 3 h after arrival. We calculated use of antenatal corticosteroids in women who gave birth between 26 and 34 weeks' gestation, when antenatal corticosteroids are known to be most beneficial. We also calculated use in women at 22-25 weeks' and 34-36 weeks' gestation. We assessed tocolytic drug use, with and without antenatal corticosteroids, in spontaneous, uncomplicated preterm deliveries at 26-34 weeks' gestation. FINDINGS: Of 303,842 recorded deliveries after 22 weeks' gestation, 17,705 (6%) were preterm. 3900 (52%) of 7547 women who gave birth at 26-34 weeks' gestation, 94 (19%) of 497 women who gave birth at 22 25 weeks' gestation, and 2276 (24%) of 9661 women who gave birth at 35-36 weeks' gestation received antenatal corticosteroids. Rates of antenatal corticosteroid use varied between countries (median 54%, range 16-91%; IQR 30-68%). Of 4677 women who were potentially eligible for tocolysis drugs, 1276 (27%) were treated with bed rest or hydration and 2248 (48%) received no treatment. beta-agonists alone (n=346, 7%) were the most frequently used tocolytic drug. Only 848 (18%) of potentially eligible women received both a tocolytic drug and antenatal corticosteroids. INTERPRETATION: Use of interventions was generally poor, despite evidence for their benefit for newborn babies. A substantial proportion of antenatal corticosteroid use occurred at gestational ages at which benefit is controversial, and use of less effective or potentially harmful tocolytic drugs was common. Implementation research and contextualised health policies are needed to improve drug availability and increase compliance with best obstetric practice. FUNDING: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects. PMID- 25128273 TI - The US diabetes epidemic: tip of the iceberg. PMID- 25128274 TI - Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985 2011: a modelling study. AB - BACKGROUND: Diabetes incidence has increased and mortality has decreased greatly in the USA, potentially leading to substantial changes in the lifetime risk of diabetes. We aimed to provide updated estimates for the lifetime risk of development of diabetes and to assess the effect of changes in incidence and mortality on lifetime risk and life-years lost to diabetes in the USA. METHODS: We incorporated data about diabetes incidence from the National Health Interview Survey, and linked data about mortality from 1985 to 2011 for 598 216 adults, into a Markov chain model to estimate remaining lifetime diabetes risk, years spent with and without diagnosed diabetes, and life-years lost due to diabetes in three cohorts: 1985-89, 1990-99, and 2000-11. Diabetes was determined by self report and was classified as any diabetes, excluding gestational diabetes. We used logistic regression to estimate the incidence of diabetes and Poisson regression to estimate mortality. FINDINGS: On the basis of 2000-11 data, lifetime risk of diagnosed diabetes from age 20 years was 40.2% (95% CI 39.2 41.3) for men and 39.6% (38.6-40.5) for women, representing increases of 20 percentage points and 13 percentage points, respectively, since 1985-89. The highest lifetime risks were in Hispanic men and women, and non-Hispanic black women, for whom lifetime risk now exceeds 50%. The number of life-years lost to diabetes when diagnosed at age 40 years decreased from 7.7 years (95% CI 6.5-9.0) in 1990-99 to 5.8 years (4.6-7.1) in 2000-11 in men, and from 8.7 years (8.4-8.9) to 6.8 years (6.7-7.0) in women over the same period. Because of the increasing diabetes prevalence, the average number of years lost due to diabetes for the population as a whole increased by 46% in men and 44% in women. Years spent with diabetes increased by 156% in men and 70% in women. INTERPRETATION: Continued increases in the incidence of diagnosed diabetes combined with declining mortality have led to an acceleration of lifetime risk and more years spent with diabetes, but fewer years lost to the disease for the average individual with diabetes. These findings mean that there will be a continued need for health services and extensive costs to manage the disease, and emphasise the need for effective interventions to reduce incidence. FUNDING: None. PMID- 25128275 TI - Tricyclic antidepressants exhibit variable pharmacological profiles at the alpha(2A) adrenergic receptor. AB - Antidepressant mechanisms of action remain shrouded in mystery, greatly hindering our ability to develop therapeutics which can fully treat patients suffering from depressive disorders. In an attempt to shed new light on this topic, we have undertaken a series of studies investigating actions of tricyclic antidepressant drugs (TCAs) at the alpha2A adrenergic receptor (AR), a centrally important receptor, dysregulation of which has been linked to depression. Our previous work established a particular TCA, desipramine, as an arrestin-biased alpha2AAR ligand driving receptor endocytosis and downregulation but not canonical heterotrimeric G protein-mediated signaling. The present work is aimed at broadening our understanding of how members of the TCA drug class act at the alpha2AAR, as we have selected the closely related but subtly different TCAs imipramine and amitriptyline for evaluation. Our data demonstrate that these drugs do also function as direct arrestin-biased alpha2AAR ligands. However, these data reveal differences in receptor affinity and in the extent/nature of arrestin recruitment to and endocytosis of alpha2AARs. Specifically, amitriptyline exhibits an approximately 14-fold stronger interaction with the receptor, is a weaker driver of arrestin recruitment, and preferentially recruits a different arrestin subtype. Extent of endocytosis is similar for all TCAs studied so far, and occurs in an arrestin-dependent manner, although imipramine uniquely retains a slight ability to drive alpha2AAR endocytosis in arrestin-null cells. These findings signify an important expansion of our mechanistic understanding of antidepressant pharmacology, and provide useful insights for future medicinal chemistry efforts. PMID- 25128276 TI - Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway. AB - OBJECTIVE: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. METHODS: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-kappaB and pro-inflammatory cytokines (TNF-alpha, IL-6, IL 1beta) in the spinal cord (L4/5) were analyzed by using Western blot. RESULTS: Administration of ALO (80mg/kg and 40mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up regulation of expressions of NF-kappaB, TNF-alpha, IL-6, IL-1beta at the dose of 80mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10mg/kg (i.p.). CONCLUSION: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-kappaB pathway. PMID- 25128277 TI - Comparison of the efficacy of nickel-titanium rotary systems with or without the retreatment instruments in the removal of gutta-percha in the apical third. AB - BACKGROUND: The purpose of this study was to compare the efficacy of nickel titanium rotary systems with or without the retreatment instruments in the removal of gutta-percha from the apical third. METHODS: The systems compared were as follows: ProTaper Universal (PT), ProTaper Universal Retreatment (PTr), Mtwo (M2) and Mtwo Retreatment (M2r). Sixty extracted mandibular incisors were treated with a crown-down technique and filled with gutta-percha and sealer. The apical diameter was standardized in 0.30 mm, 1 mm from the apex. The teeth were distributed into 4 experimental groups: PT, PTr, M2 and M2r. In PTr and M2r groups, filling materials were removed by PTr/M2r followed by root canals preparation up to a PT F4/M2 40; in groups PT/M2, the filling materials were removed and the root canals were prepared by PT up to a PT F4/M2 up to a M2 40. The roots were split and photomicrographing. The percentage of clean area in the apical 5 mm was calculated using software. Data were analyzed with the Kruskal Wallis test. RESULTS: Remaining material was found in all hemisections and there was no statistically significant difference between the groups (p = 0.09). Considering the surface of the canal walls of all teeth, the mean of the percentage of clean area was 54%. CONCLUSIONS: Considering the applied methodology, remaining filling material was found in all hemisections, regardless of the retreatment technique and PT or M2 were as effective as PTr/PT or M2r/M2. PMID- 25128278 TI - Comparison between rapid and slow palatal expansion: evaluation of selected periodontal indices. AB - OBJECTIVES: The aim of this pilot study was to evaluate the periodontal effects during rapid palatal expansion (RPE) or slow palatal expansion (SPE) and to compare them by means of some clinical indices, in order to establish the possible differences and advantages of one of these treatments in periodontal terms. METHODS: 10 patients (aged 6 to 7 years; average age 6.3 years) were submitted to RPE treatment and other 10 patients (aged 6 to 8 years, average age 6.3 years) to SPE treatment. They were treated with the Haas expander. The selected clinical indices (plaque index, PI; papillary bleeding index, PBI; probing pocket depth, PPD) were collected three times during the treatment (t0, detected 7 days after the periodontal prophylaxis, at the beginning of the active orthodontic therapy; t1, detected during the active therapy; t2, detected after retention). All measurements were performed by the same examiner. The protocol was approved by the ethics committee. RESULTS: The effects of the prophylaxis were excellent to control inflammation and dental plaque before the beginning of the orthodontic-orthopaedic treatment, as in both the two groups, the PI and the PBI values were equal to 0.In the group receiving slow expansion, the PPD remained unchanged from t0 to t1, while it significantly increased from t0 to t1 in the group of rapid expansion. At t2 the values of the two groups returned to be overlapping. CONCLUSIONS: Both rapid and slow expansion treatments present potential irritation effect (increase of PI index and PBI index) on the periodontium, suggested by the significant increase of PI and PBI from t0 to t1 in both the two groups; therefore prophylaxis and periodic controls are very important. There are no long-term benefits that might be referred unequivocally to one of the two treatments in terms of periodontal consequences, as demonstrated by the lack of significant differences between the two groups at t2. PMID- 25128279 TI - Functional genetic variation in the serotonin 5-HTTLPR modulates brain damage in frontotemporal dementia. AB - In frontotemporal dementia (FTD), nonmodifiable (genetic background) and modifiable (cognitive reserve [CR]) factors might interact in affecting frontotemporal damage. Serotoninergic dysfunction has been suggested as a key factor in FTD pathogenesis. 5-HTTLPR polymorphism on SCLA4 gene modulates the serotoninergic transmission. To evaluate the impact of 5-HTTLPR polymorphism on regional cerebral blood flow (rCBF) and its possible interaction with CR, 76 FTD patients with a 5-HTTLPR genotyping were recruited. All subjects underwent neuropsychological assessment and single-photon emission computed tomography imaging. Reserve index (RI) was computed from educational and occupational attainments, as proxy measure of CR. 5-HTTLPR analysis evidenced 14 S/S, 24 L/L, and 38 S/L carriers. No neuropsychological/behavioral differences were present. At the same disease stage, L/L carriers have a greater bilateral frontal rCBF decrease. Patients with higher RI had greater damage in right frontal and temporal regions. The additive effect of 5-HTTLPR polymorphism and RI was characterized by greater frontal rCBF deficit. 5-HTTLPR and CR act together to counteract brain pathology in FTD. Further studies are warranted to test the serotonin role in monogenic forms of FTD. PMID- 25128281 TI - Iatrogenic traumatic intracranial aneurysm after endoscopic sinus surgery. AB - Iatrogenic traumatic intracranial aneurysms are rare, but their clinical impact is significant secondary to their risk of intracranial hemorrhage and in their frequent complexity in management. We report an adult patient with a history of chronic sinusitis who, while undergoing elective endoscopic polypectomy, suffered an iatrogenic injury to an A2 segment branch of the left anterior cerebral artery, resulting in a pseudoaneurysm. Management included endovascular coiling and a bicoronal craniotomy approach, using a split-thickness cranial graft and abdominal fat graft to repair the associated left cribriform plate defect. PMID- 25128282 TI - Vasodilatation of multiple cerebral arteries in early stage of stroke-like episode with MELAS. AB - We describe a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), with multiple cerebral vasodilatations in a stroke-like episode visualised by using magnetic resonance angiography (MRA) and CT angiography (CTA). In the acute stroke-like episode stage, T2-weighted and fluid-attenuated inversion recovery MRI showed high intensity areas in the left occipital area. In addition, MRA and CTA revealed prominent dilatation of the left posterior cerebral artery and temporal branches of the middle cerebral artery with focal hyperperfusions using CT perfusion (CTP) that corresponded to the MRI. After 10 days, with the development of aphasia, MRI indicated the lesions had spread to the temporal and parietal regions, and this distribution was not confined to major vascular territories. The patient's symptoms gradually improved, accompanied by the attenuation of MRI, CTA, and CTP findings. These characteristic features along with the MRI changes that spread beyond vascular boundaries and the multiple cerebral vasodilatations prior to the development of clinical symptoms are not fully explained by the mitochondrial angiopathy or cytopathy theories. These findings provide further evidence supporting neuronal hyperexcitability in stroke-like episodes of MELAS. PMID- 25128283 TI - The impact of prior knowledge from participant instructions in a mock crime P300 Concealed Information Test. AB - In P300-Concealed Information Tests used with mock crime scenarios, the amount of detail revealed to a participant prior to the commission of the mock crime can have a serious impact on a study's validity. We predicted that exposure to crime details through instructions would bias detection rates toward enhanced sensitivity. In a 2 * 2 factorial design, participants were either informed (through mock crime instructions) or naive as to the identity of a to-be-stolen item, and then either committed (guilty) or did not commit (innocent) the crime. Results showed that prior knowledge of the stolen item was sufficient to cause 69% of innocent-informed participants to be incorrectly classified as guilty. Further, we found a trend toward enhanced detection rate for guilty-informed participants over guilty-naive participants. Results suggest that revealing details to participants through instructions biases detection rates in the P300 CIT toward enhanced sensitivity. PMID- 25128280 TI - Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies. AB - Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on magnetic resonance imaging. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We investigated the pattern and magnitude of the atrophy rates from 2 serial MRIs in autopsy-confirmed DLB patients (n = 20) and mixed DLB/AD patients (n = 22), compared with AD (n = 30) and elderly nondemented control subjects (n = 15), followed antemortem. DLB patients without significant AD-type pathology were characterized by lower global and regional rates of atrophy, similar to control subjects. The mixed DLB/AD patients displayed greater atrophy rates in the whole brain, temporoparietal cortices, hippocampus and amygdala, and ventricle expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy rates correlated with Braak neurofibrillary tangle stage, cognitive decline, and progression of motor symptoms. Global and regional atrophy rates are associated with AD-type pathology in DLB, and these rates can be used as biomarkers of AD progression in patients with LB pathology. PMID- 25128284 TI - Opioid-induced hyperalgesia (OIH): a real clinical problem or just an experimental phenomenon? AB - Although opioid-induced hyperalgesia (OIH) is mentioned as a potential cause of opioid dose escalation without adequate analgesia, true evidence in support of this notion is relatively limited. Most studies conducted in the context of acute and experimental pain, which seemingly demonstrated evidence for OIH, actually might have measured other phenomena such as acute opioid withdrawal or tolerance. OIH studies in patients with chronic pain have used various experimental pain models (such as cold pain tolerance or heat pain intensity). Therefore, the fact that they have yielded inconsistent results is hard to interpret. Thus far, with the exception of a few clinical case reports on OIH in patients with cancer pain and one prospective study in patients with chronic neuropathic pain, evidence for OIH in patients with chronic or cancer-related pain is lacking. Whether experimental pain models are necessary for establishing the clinical diagnosis of OIH, and which specific model is preferred, are yet to be determined. PMID- 25128285 TI - C-reactive protein, depressive symptoms, and risk of diabetes: results from the English Longitudinal Study of Ageing (ELSA). AB - OBJECTIVES: Raised levels of C-reactive protein (CRP), an inflammatory biomarker, and depressive symptoms are both independently linked to risk of diabetes. The purpose of this study was to assess the joint association of CRP and depressive symptomatology with diabetes incidence in a representative sample of English people >=50 years old. METHOD: Data were from the English Longitudinal Study of Ageing, a prospective study of community-dwelling older adults. The sample was comprised of 4955 participants without self-reported doctor-diagnosed diabetes at baseline. High CRP level was dichotomized as >3 mg/L. Elevated depressive symptomatology was defined as >=4 using the 8-item Center for Epidemiologic Studies Depression Scale. Incident diabetes was determined based on newly self reported doctor-diagnosed diabetes. Cox proportional hazard regressions were used to examine the association between CRP and depressive symptoms with incidence of type 2 diabetes. RESULTS: During approximately 63.2 months of follow-up, 194 participants reported diabetes diagnosis. After adjustment for socio demographics, lifestyle behaviors, clinical factors, and BMI, the hazard ratio for diabetes was 1.63 (95% CI 0.88-3.01) for people with elevated depressive symptoms only, 1.43 (95% CI 0.99-2.07) for people with high CRP only, and 2.03 (95% CI 1.14-3.61) for people with both high CRP and elevated depressive symptoms. CONCLUSION: The presence of both high CRP levels and elevated depressive symptoms was associated with risk of diabetes. Further investigation into this relationship could aid in understanding the mechanisms underlying inflammation, depression, and diabetes. PMID- 25128286 TI - Understanding the impact of visual arts interventions for people living with dementia: a realist review protocol. AB - BACKGROUND: Arts-based activities are being increasingly suggested as a valuable activity for people living with dementia in terms of countering the negative aspects of their condition. The potential for such programmes to improve a broad range of psychosocial outcomes is suggested in some studies. However, there is largely an absence of rigorous methodology to demonstrate the benefits, and research results are mixed. Practice variability in terms of the content, contexts and implementation of such interventions raises challenges in terms of identifying an optimal arts programme model that could be adopted by other service providers. Understanding how interventions may have the best chance at broad implementation success and uptake is limited. METHODS/DESIGN: A realist review will be undertaken. This aims to understand how visual arts interventions influence outcomes in people living with dementia. The review will explore how the context, that is the circumstances which enable or constrain, affect outcomes through the activation of mechanisms. An early scoping search and a stakeholder survey formulated the preliminary programme theory. A systematic literature search across a broad range of disciplines (arts, humanities, social sciences, health) will be undertaken to identify journal articles and grey literature. Data will be extracted in relation to the programme theory, contextual factors, mechanisms and outcomes and their configurations, background information about the study design and participant characteristics, detail about the quantity ('dose') of an intervention, theoretical perspectives proposed by the authors of the paper and further theorising by the reviewer. Thematic connections/patterns will be sought across the extracted data, identifying patterns amongst contextual factors, the mechanisms they trigger and the associated outcomes. DISCUSSION: Along with stakeholder engagement and validation, this review will help inform the development of an optimal, replicable arts intervention for people with dementia as part of our broader research programme, titled 'Dementia and Imagination' (funded by the Arts and Humanities Research Council). Forthcoming work under this programme of research will test this theoretically informed intervention in three different geographical areas of the UK. The production of freely available practice guidance is a key aspect of dissemination. TRIAL REGISTRATION: PROSPERO registration number CRD42014008702. PMID- 25128287 TI - Trends and implications for achieving VISION 2020 human resources for eye health targets in 16 countries of sub-Saharan Africa by the year 2020. AB - BACKGROUND: Development of human resources for eye health (HReH) is a major global eye health strategy to reduce the prevalence of avoidable visual impairment by the year 2020. Building on our previous analysis of current progress towards key HReH indicators and cataract surgery rates (CSRs), we predicted future indicator achievement among 16 countries of sub-Saharan Africa by 2020. METHODS: Surgical and HReH data were collected from national eye care programme coordinators on six practitioner cadres: ophthalmologists, cataract surgeons, ophthalmic clinical officers, ophthalmic nurses, optometrists and 'mid level refractionists' and combined them with publicly available population data to calculate practitioner-to-population ratios and CSRs. Data on workforce entry and exit (2008 to 2010) was used to project practitioner population and CSR growth between 2011 and 2020 in relation to projected growth in the general population. Associations between indicator progress and the presence of a non physician cataract surgeon cadre were also explored using Wilcoxon rank sum tests and Spearman rank correlations. RESULTS: In our 16-country sample, practitioner per million population ratios are predicted to increase slightly for surgeons (ophthalmologists/cataract surgeons, from 3.1 in 2011 to 3.4 in 2020) and ophthalmic nurses/clinical officers (5.8 to 6.8) but remain low for refractionists (including optometrists, at 3.6 in 2011 and 2020). Among countries that have not already achieved target indicators, however, practitioner growth will be insufficient for any additional countries to reach the surgeon and refractionist targets by year 2020. Without further strategy change and investment, even after 2020, surgeon growth is only expected to sufficiently outpace general population growth to reach the target in one country. For nurses, two additional countries will achieve the target while one will fall below it. In 2011, high surgeon practitioner ratios were associated with high CSR, regardless of the type of surgeon employed. The cataract surgeon workforce is growing proportionately faster than the ophthalmologist. CONCLUSIONS: The HReH workforce is not growing fast enough to achieve global eye health targets in most of the sub-Saharan countries we surveyed by 2020. Countries seeking to make rapid progress to improve CSR could prioritise investment in training new cataract surgeons over ophthalmologists and improving surgical output efficiency. PMID- 25128288 TI - Vitamin B12 deficiency with combined hematological and neuropsychiatric derangements: a case report. AB - INTRODUCTION: Although vitamin B12 deficiency is a well-known cause of hematological and neuropsychiatric illness, the presentation of combined severe pancytopenia, demyelination and prominent psychiatric impairment is rare. CASE PRESENTATION: We present a case of a previously healthy 55-year-old East African man with severe vitamin B12 deficiency (serum vitamin B12 22pmol/L) secondary to pernicious anemia. He had a severe hypoproliferative megaloblastic anemia with hemolysis (hemoglobin 61g/L, mean corpuscular volume 99fL, reticulocytes 0.8%, haptoglobin undetectable), leukopenia (2.7*109/L), thrombocytopenia (96*109/L), ataxia with central demyelination, and megaloblastic madness. The patient's anemia, myelopathy and psychiatric condition responded well to parenteral vitamin B12 replacement therapy, with significant improvement seen within weeks. CONCLUSION: Hematological manifestations of vitamin B12 deficiency are typically inversely correlated with the presence and severity of neuropsychiatric impairment. Although uncommon, a presentation with severe hematological and neuropsychiatric disease can occur, as illustrated by this case. Its presence may help guide diagnosis as well as provide clinically important prognostic information. PMID- 25128289 TI - Patch-testing for the management of hypersensitivity reactions to second-line anti-tuberculosis drugs: a case report. AB - BACKGROUND: The second-line anti-tuberculosis drugs used in the treatment of multidrug-resistant tuberculosis often cause adverse events, especially in patients co-infected with the human immunodeficiency virus. Severe hypersensitivity reactions due to these drugs are rare and there is little published experience to guide their management. CASE PRESENTATION: A 17-year old Indian female multidrug-resistant tuberculosis patient co-infected with human immunodeficiency virus developed a hypersensitivity reaction after starting second-line anti-tuberculosis treatment in Mumbai, India. The patient was being treated with kanamycin, moxifloxacin, para-aminosalicylic acid, cycloserine, clofazimine, and amoxicillin-clavulanic acid. Twenty-four hours later, the patient developed generalized urticaria, morbilliform rash and fever. All drugs were suspended and the patient was hospitalised for acute management. Skin patch testing was used to identify drugs that potentially caused the hypersensitivity reaction; results showed a strong reaction to clofazimine, moderate reaction to kanamycin and mild reaction to cycloserine. An interim second-line anti tuberculosis regimen was prescribed; cycloserine and kanamycin were then re challenged one-by-one using incremental dosing, an approach that allowed clinicians to re-introduce these drugs promptly and safely. The patient is currently doing well. CONCLUSIONS: This is the first case-report of a multidrug resistant tuberculosis patient co-infected with the human immunodeficiency virus with hypersensitivity reaction to multiple second-line anti-tuberculosis drugs. Skin patch-testing and controlled re-challenge can be a useful management strategy in such patients. There is an urgent need for second-line anti tuberculosis regimens that are more effective, safe and better tolerated. PMID- 25128290 TI - Cultural differences in postnatal quality of life among German-speaking women - a prospective survey in two countries. AB - BACKGROUND: Assessment of quality of life after childbirth is an important health outcome measurement for new mothers and is of special interest in midwifery. The Mother-Generated Index (MGI) is a validated instrument to assess postnatal quality of life. The tool has not been applied for making a cross-cultural comparison before. This study investigated (a) responses to the MGI in German speaking women in Germany and Switzerland; and (b) associations between MGI scores on the one hand and maternity and midwifery care on the other. METHODS: A two-stage survey was conducted in two rural hospitals 10 km apart, on opposite sides of the German-Swiss border. The questionnaires included the MGI and questions on socio-demographics, physical and mental health and maternity care, and were distributed during the first days after birth and six weeks postpartum. Parametric and non-parametric tests were computed with the statistical programme SPSS. RESULTS: A total of 129 questionnaires were returned an average of three days after birth and 83 in the follow-up after seven weeks. There were no statistically significant differences in the MGI scores between the German and the Swiss women (p = 0.22). Significantly more favourable MGI scores were found associated with more adequate information during pregnancy (p = 0.02), a more satisfactory birth experience (p < .01), epidural anaesthesia (p < 0.01), more information (p = 0.01) and better support (p = 0.02) during the time in hospital and less disturbed sleep (p < 0.01). Significantly lower MGI scores were associated with the presence of a private doctor during birth (p = 0.01) and with exclusive breastfeeding during the first postnatal days (p = 0.04). CONCLUSION: The MGI scores of these German-speaking women were higher than those in other studies reported previously. Thus the tool may be able to detect differences in postnatal quality of life among women with substantially divergent cultural backgrounds. Shortcomings in maternity and midwifery care were detected, as for example the inadequate provision of information during pregnancy, a lack of individualised postpartum care during the hospital stay and insufficient support for exclusively breastfeeding mothers. The MGI is an appropriate instrument for maternity care outcome measurement in cross-cultural comparison research. PMID- 25128291 TI - Nitrogen limitation and high density responses in rice suggest a role for ethylene under high density stress. AB - BACKGROUND: High density stress, also known as intraspecies competition, causes significant yield losses in a wide variety of crop plants. At the same time, increases in density tolerance through selective breeding and the concomitant ability to plant crops at a higher population density has been one of the most important factors in the development of high yielding modern cultivars. RESULTS: Physiological changes underlying high density stress were examined in Oryza sativa plants over the course of a life cycle by assessing differences in gene expression and metabolism. Moreover, the nitrogen limitation was examined in parallel with high density stress to gain a better understanding of physiological responses specific to high density stress. While both nitrogen limitation and high density resulted in decreased shoot fresh weight, tiller number, plant height and chlorophyll content, high density stress alone had a greater impact on physiological factors. Decreases in aspartate and glutamate concentration were found in plants grown under both stress conditions; however, high density stress had a more significant effect on the concentration of these amino acids. Global transcriptome analysis revealed a large proportion of genes with altered expression in response to both stresses. The presence of ethylene-associated genes in a majority of density responsive genes was investigated further. Expression of ethylene biosynthesis genes ACC synthase 1, ACC synthase 2 and ACC oxidase 7 were found to be upregulated in plants under high density stress. Plants at high density were also found to up regulate ethylene-associated genes and senescence genes, while cytokinin response and biosynthesis genes were down regulated, consistent with higher ethylene production. CONCLUSIONS: High density stress has similar but greater impact on plant growth and development compared to nitrogen limitation. Global transcriptome changes implicate ethylene as a volatile signal used to communicate proximity in under dense population growth condition and suggest a role for phytohormones in high density stress response in rice plants. PMID- 25128293 TI - Role of statherin in oral carcinogenesis. PMID- 25128292 TI - A biomechanical cause of low power production during FES cycling of subjects with SCI. AB - BACKGROUND: The goal of Functional Electrical Stimulation (FES) cycling is to provide the health benefits of exercise to persons with paralysis. To achieve the greatest health advantages, patients should produce the highest possible mechanical power. However, the mechanical power output (PO) produced during FES cycling is very low. Unfavorable biomechanics is one of the important factors reducing PO. The purpose of this study was to investigate the primary joints and muscles responsible for power generation and the role of antagonistic co contraction in FES cycling. METHODS: Sixteen subjects with complete spinal cord injury (SCI) pedaled a stationary recumbent FES tricycle at 60 rpm and a workload of 15 W per leg, while pedal forces and crank angle were recorded. The joint muscle moments, power and work were calculated using inverse dynamics equations. RESULTS: Two characteristic patterns were found; in 12 subjects most work was generated by the knee extensors in the propulsion phase (83% of total work), while in 4 subjects most work was shared between by the knee extensors (42%) and flexors (44%), respectively during propulsive and recovery phases. Hip extensors produced only low net work (12 & 7%). For both patterns, extra concentric work was necessary to overcome considerable eccentric work (-82 & -96%). CONCLUSIONS: The primary power sources were the knee extensors of the quadriceps and the knee flexors of the hamstrings. The antagonistic activity was generally low in subjects with SCI because of the weakness of the hamstrings (compared to quadriceps) and the superficial and insufficient hamstring mass activation with FES. PMID- 25128294 TI - Incorporation of salivary metabolomics in oral cancer diagnostics. PMID- 25128295 TI - RAGE, inflammation and oral cancer: recreating the connexion. PMID- 25128296 TI - Influence of a prudent diet on circulating cathepsin S in humans. AB - BACKGROUND: Increased circulating cathepsin S levels have been linked to increased risk of cardiometabolic diseases and cancer. However, whether cathepsin S is a modifiable risk factor is unclear. We aimed to investigate the effects of a prudent diet on plasma cathepsin S levels in healthy individuals. FINDINGS: Explorative analyses of a randomized study were performed in 88 normal to slightly overweight and hyperlipidemic men and women (aged 25 to 65) that were randomly assigned to ad libitum prudent diet, i.e. healthy Nordic diet (ND) or a control group (habitual Western diet) for 6 weeks. Whereas all foods in the ND were provided, the control group was advised to consume their habitual diet throughout the study. The ND was in line with dietary recommendations, e.g. low in saturated fats, sugars and salt, but high in plant-based foods rich in fibre and unsaturated fats.The ND significantly decreased cathepsin S levels (from 20.1 (+/-4.0 SD) to 19.7 MUg/L (+/-4.3 SD)) compared with control group (from 18.2 (+/ 2.9 SD) to 19.1 MUg/L (+/-3.8 SD)). This difference remained after adjusting for sex and change in insulin sensitivity (P = 0.03), and near significant after adjusting for baseline cathepsin S levels (P = 0.06), but not for change in weight or LDL-C. Changes in cathepsin S levels were directly correlated with change in LDL-C. CONCLUSIONS: Compared with a habitual control diet, a provided ad libitum healthy Nordic diet decreased cathepsin S levels in healthy individuals, possibly mediated by weight loss or lowered LDL-C. These differences between groups in cathepsin S were however not robust and therefore need further investigation. PMID- 25128297 TI - Efficacy of Bacillus thuringiensis var. israelensis against malaria mosquitoes in northwestern Burkina Faso. AB - BACKGROUND: In Sub Saharan Africa malaria remains one of the major health problems and its control represents an important public health measure. Integrated malaria control comprises the use of impregnated mosquito nets and indoor residual spraying. The use of drugs to treat patients can create additional pressure on the equation of malaria transmission. Vector control may target the adult mosquitoes or their aquatic larval stages. Biological larvicides such as Bacillus thuringiensis israelensis (Bti) represent a promising approach to support malaria control programs by creating additional pressure on the equation of malaria transmission. METHODS: In this study we examined the efficacy of a water-dispersible granule formulation (WDG) of the biological larvicide Bti (VectoBac(r)) against wild Anopheles spp. larvae. Different concentrations of the larvicide were tested in standardized plastic tubs in the field against untreated controls. In weekly intervals tubs were treated with fixed concentrations of larvicide and the percentage reduction of larvae and pupae was calculated. RESULTS: All used concentrations successfully killed 100 percent of the larvae within 24 hours, while the higher concentrations showed a slightly prolonged residual effect. Natural reconolization of larvae took place after two and three days respectively, late instar larvae were not found before 5 days after treatment. For the higher concentrations, up to three days no new larvae were found, implicating that the residual effect of WDG in tropical conditions is approximately one to two days. The overall pupae reduction in treated tubs was 98.5%. CONCLUSIONS: Biological larviciding with Bti can be a promising, additional tool in the fight against malaria in Africa. Environmental particularities in tropical Africa, first and foremost the rapid development of mosquitoes from oviposition to imago have to be taken into account before implementing such counter measures in national or international vector control programs. Nonetheless biological larviciding seems to be an appropriate measure for selected conditions, offering a significant contribution to the future of malaria control. PMID- 25128298 TI - Comparative study on the suitability of two techniques for measuring the transfer of lipophilic drug models from lipid nanoparticles to lipophilic acceptors. AB - Due to their particle size in the submicrometer range, lipid nanoparticles are suitable for parenteral administration. In order to obtain information on their potential in vivo performance, a simple and effective in vitro assay to evaluate the drug release behavior of such particles is required. This study compares the use of different experimental setups for this purpose. Lipid nanoparticles from trimyristin which were loaded with fluorescent lipophilic drug models (a temoporfin and Nile red) were used as donor particles. The transfer of the two drug models to multilamellar vesicles (MLV) and emulsion droplets as lipophilic acceptor compartments was examined. The determination of the transferred substance was performed either after separation by centrifugation or by an in situ flow cytometric technique. The transfer of temoporfin was slow to the acceptor MLV and very rapid to the acceptor emulsion. With both acceptors, the transfer of temoporfin stopped at a concentration much lower than the theoretical equilibrium values. The transfer of the less lipophilic drug Nile red was very rapid to both acceptors with equilibrium concentrations close to the expected values. The transfer results of temoporfin especially to the acceptor MLV obtained with the two detection techniques were comparable while the centrifugation technique indicated an apparently higher Nile red transfer rate than the flow cytometric technique. Both techniques are equally suitable to study the transfer of temoporfin, while the flow cytometric technique is advantageous to measure the very rapid transfer of Nile red. PMID- 25128299 TI - Alpha-fetoprotein level as a biomarker of liver fibrosis status: a cross sectional study of 619 consecutive patients with chronic hepatitis B. AB - BACKGROUND: Hepatitis B virus (HBV) infection is a serious public health problem worldwide. This study aimed to investigate the relationship between serum alpha fetoprotein (AFP) levels and pathological stages of liver biopsy in patients with chronic hepatitis B (CHB). METHODS: The study included 619 patients who were diagnosed with CHB from March 2005 to December 2011. AFP levels were measured by electrochemiluminescence. Liver biopsy samples were classified into five levels of inflammation (G) and fibrosis (S) stages, according to the Chinese guidelines for prevention and treatment of viral hepatitis. Two multivariable ordinal regression models were performed to determine associations between AFP, GGT, and APRI (AST/PLT ratio) and stages of inflammation and fibrosis. RESULTS: Significant positive and moderate correlations were shown between AFP levels and inflammation stages and between AFP levels and fibrosis stages (rho = 0.436 and 0.404, p < 0.001). Median values of AFP at liver fibrosis stages S0-1, S2, S3, and S4 were 3.0, 3.4, 5.4, and 11.3 ng/ml, respectively, and median APRI (AST/PLT ratio) was 0.41. Receiver operating characteristic (ROC) curve analyses revealed that the areas under the curves (AUCs) were 0.685, 0.727, and 0.755 (all p <0.001) for judging inflammation stages of G >= 2, G >= 3, G = 4 by AFP; and 0.691, 0.717, and 0.718 (all p <0.001) for judging fibrosis stages of S >= 2, S >= 3, and S = 4 by AFP. APRI levels showed significant positive and moderate correlations with inflammation stages (rho = 0.445, p < 0.001). AST, GGT, and APRI levels showed significant positive but very weak to weak correlations with fibrosis stages (rho = 0.137, 0.237, 0.281, p < 0.001). CONCLUSIONS: Serum AFP levels increased as pathological levels of inflammation and fibrosis increased in CHB patients. Our data showed the clinical significance of serum AFP levels in diagnosing liver inflammation and fibrosis. Assessment of liver pathology may be improved by creating a predictive mathematical model by which AFP levels with other biomarkers. PMID- 25128302 TI - An Indian eye to personalized medicine. AB - Acknowledging the successful sequencing of the human genome and the valuable insights it has rendered, genetic drafting of non-human organisms can further enhance the understanding of modern biology. The price of sequencing technology has plummeted with time, and there is a noticeable enhancement in its implementation and recurrent usage. Sequenced genome information can be contained in a microarray chip, and then processed by a computer system for inferring analytics and predictions. Specifically, smart cards have been significantly applicable to assimilate and retrieve complex data, with ease and implicit mobility. Herein, we propose "The G-Card", a development with respect to the prevalent smart card, and an extension to the Electronic Health Record (EHR), that will hold the genome sequence of an individual, so that the medical practitioner can better investigate irregularities in a patient's health and hence recommend a precise prognosis. PMID- 25128301 TI - Evaluation of respondent-driven sampling in a study of urban young men who have sex with men. AB - Evidence suggests that respondent-driven sampling (RDS) is an efficient approach to sampling among varied populations of adult men who have sex with men (MSM) both in the USA and abroad, although no studies have yet evaluated its performance among younger MSM, a population with a steep rise in HIV infection in recent years. Young MSM (YMSM) may differ in terms of their connectedness to other YMSM (e.g., due to evolving sexual identity, internalization of sexual minority stigma, and lack of disclosure to others) and mobility (e.g., due to parental monitoring) which may inhibit the sampling process. The aims of this study were to evaluate the efficiency and effectiveness of RDS-based sampling among young urban MSM and to identify factors associated with recruitment success. We hypothesized that demographic, social, behavioral, and network factors, including racial/ethnic minority status, homelessness (i.e., as an indicator of socioeconomic marginalization), HIV-positive status, substance use problems, gay community connectedness, and network size would be positively related to recruitment productivity, while sexual minority stigmatization, environmental barriers (e.g., parental monitoring), and meeting sex partners on the internet (i.e., virtual venue) would be negatively related to recruitment productivity. Between December 2009 and February 2013, we used RDS to recruit a sample of 450 YMSM, ages 16-20. Findings suggest that the use of RDS for sampling among YMSM is challenging and may not be feasible based on the slow pace of recruitment and low recruitment productivity. A large number of seeds (38 % of the sample, n = 172) had to be added to the sample to maintain a reasonable pace of recruitment, which makes use of the sample for RDS-based population estimates questionable. In addition, the prevalence of short recruitment chains and segmentation in patterns of recruitment by race/ethnicity further hamper the network recruitment process. Thus, RDS was not particularly efficient in terms of the rate of recruitment or effective in generating a representative sample. Hypotheses regarding factors associated with recruitment success were supported for network size and internalized stigma (but not other factors), suggesting that participants with larger network sizes or high levels of internalized stigma may have more and less success recruiting others, respectively. PMID- 25128300 TI - The biography of the immune system and the control of cancer: from St Peregrine to contemporary vaccination strategies. AB - BACKGROUND: The historical basis and contemporary evidence for the use of immune strategies for prevention of malignancies are reviewed. Emphasis is focussed on the Febrile Infections and Melanoma (FEBIM) study on melanoma and on malignancies that seem to be related to an overexpression of human endogenous retrovirus K (HERV-K). DISCUSSION: It is claimed that, as a result of recent observational studies, measures for prevention of some malignancies such as melanoma and certain forms of leukaemia are already at hand: vaccination with Bacille Calmette Guerin (BCG) of new-borns and vaccination with the yellow fever 17D (YFV) vaccine of adults. While the evidence of their benefit for prevention of malignancies requires substantiation, the observations that vaccinations with BCG and/or vaccinia early in life improved the outcome of patients after surgical therapy of melanoma are of practical relevance as the survival advantage conferred by prior vaccination is greater than any contemporary adjuvant therapy. SUMMARY: The reviewed findings open a debate as to whether controlled vaccination studies should be conducted in patients and/or regions for whom/where they are needed most urgently. A study proposal is made and discussed. If protection is confirmed, the development of novel recombinant vaccines with wider ranges of protection based, most likely, on BCG, YFV or vaccinia, could be attempted. PMID- 25128303 TI - Management of Composite Tissue Defect of the Midfoot With a Free Anterolateral Thigh Flap and Iliac Bone Graft: A Case Report. AB - Composite tissue defects of the midfoot with extensive bone and soft tissue loss represent a unique challenge because they can lead to primary amputation if not reconstructed. One should repair both the bone structure and the soft tissue to obtain satisfactory foot function for basic daily activities. In the present study, we report on a case in which we successfully reconstructed an extensive midfoot defect with iliac bone grafts for metatarsal reconstruction and an anterolateral thigh flap for soft tissue coverage. This technique is a safe, reliable, and functional method, offering single-stage reconstruction compared with other microsurgical techniques used for such defects. PMID- 25128304 TI - A Meta-Analysis for Postoperative Complications in Tibial Plafond Fracture: Open Reduction and Internal Fixation Versus Limited Internal Fixation Combined With External Fixator. AB - The treatment of tibial plafond fractures is challenging to foot and ankle surgeons. Open reduction and internal fixation and limited internal fixation combined with an external fixator are 2 of the most commonly used methods of tibial plafond fracture repair. However, conclusions regarding the superior choice remain controversial. The present meta-analysis aimed to quantitatively compare the postoperative complications between open reduction and internal fixation and limited internal fixation combined with an external fixator for tibial plafond fractures. Nine studies with 498 fractures in 494 patients were included in the present study. The meta-analysis found no significant differences in bone healing complications (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.68 to 2.01, p = .58], nonunion (RR 1.09, 95% CI 0.51 to 2.36, p = .82), malunion or delayed union (RR 1.24, 95% CI 0.57 to 2.69, p = .59), superficial (RR 1.56, 95% CI 0.43 to 5.61, p = .50) and deep (RR 1.89, 95% CI 0.62 to 5.80) infections, arthritis symptoms (RR 1.20, 95% CI 0.92 to 1.58, p = .18), or chronic osteomyelitis (RR 0.31, 95% CI 0.05 to 1.84, p = .20) between the 2 groups. PMID- 25128305 TI - Self-reported quality of life and diabetic foot infections. AB - Foot infections in patients with diabetes mellitus (DM) are serious complications that can result in hospitalization, the need for amputation, and premature mortality. To the best of our knowledge, no published studies have specifically investigated the effect of diabetic foot infection (DFI) on patient quality of life. The aim of the present study was to compare the self-reported assessments of quality of life in patients hospitalized with DFIs with those from a group of patients without foot infections. We evaluated a study group of 47 patients who had been hospitalized with DFIs and a control group of 47 patients with DM who did not have any complaints referable to their foot or ankle. The self-reported outcomes were assessed using the Medical Outcomes Study short form 36-item health survey (SF-36) and the Foot and Ankle Ability Measurement. Patients hospitalized with DFIs had significantly reduced self-reported SF-36 scores in all 8 subscales compared with the cohort of patients with DM without foot complaints. The SF-36 physical component and mental component scores were significantly reduced in patients with DFIs, indicating a negative effect on overall health. Self-reported lower extremity function was also negatively affected with significantly lower Foot and Ankle Measurement activity of daily living and sports scores for patients with DFI. The present study has demonstrated the profoundly negative affect that moderate and severe DFIs have on self-reported quality of life, affecting both physical and mental well-being and lower extremity function. PMID- 25128306 TI - Bilateral Ankle and Subtalar Joint Fusion Secondary to Guillain Barre-Induced Foot Drop. AB - Guillain-Barre syndrome is a serious disorder that occurs when the body's immune system mistakenly attacks the peripheral nervous system. This leads to nerve inflammation and damage that can cause muscle weakness and/or paralysis, including foot drop. Therapy ranges from supportive measures, such as physical therapy, to surgical intervention. It appears from the published data that these patients, generally, have been left to their own devices, because no known cure is available, necessitating reliance on others for their daily activities and ambulation. We present a unique surgical option, with a follow-up period of 24 months, in which bilateral subtalar and ankle fusion allowed unassisted ambulation to a patient who might otherwise have never walked again. PMID- 25128307 TI - Comparison of postinjection protocols after intratendinous Achilles platelet-rich plasma injections: a cadaveric study. AB - The purpose of the present investigation was to evaluate the distribution of intratendinous injected platelet-rich plasma (PRP) after 15 minutes of prone resting versus immediate manipulation simulating weightbearing. Ten cadaveric lower limbs were injected under ultrasound guidance with PRP dyed with India blue ink. The dyed PRP was injected into the mid-portion of the Achilles tendon, after which 5 specimens were placed in the prone position for 15 minutes (simulating rest) and the remaining 5 specimens were manipulated through 100 cycles of ankle dorsiflexion and plantarflexion (simulating walking). Thereafter, the specimens were dissected, and the distribution of the India blue dye was ascertained. In the simulated rest group, every specimen showed dyed PRP in the Achilles tendon and in the space between the paratenon and tendon. The median craniocaudal spread of the PRP was 140 (range 125 to 190) mm. In 4 of the simulated rest tendons (80%), the distribution of PRP extended across the entire transverse plane width of the tendon. In the simulated motion group, every specimen showed dyed PRP extending across the entire transverse plane width of the tendon and in the space between the paratenon and tendon. The median craniocaudal spread was 135 (range 115 to 117) mm. No statistically significant difference was found in the amount of craniocaudal spread between the simulated motion and rest groups. In conclusion, it does not appear to matter whether the ankle has been moved through its range of motion or maintained stationary during the first 15 minutes after PRP injection into the mid-portion of the Achilles tendon. The precise meaning of this information in the clinical realm remains to be discerned. PMID- 25128308 TI - A retrospective study of two Lapidus groups, each with a different method of rail application. AB - To date, few studies discussing the use of rail external fixation for the Lapidus procedure have presented acceptable complication rates. At least 1 study has suggested the technique is not recommended for routine use with this procedure. We present 2 methods of external fixation application and 2 protocols of early postoperative weightbearing in 25 patients, with a marked decrease in complication rates from previously published studies. A retrospective study of 25 patients (within 2 patient groups) was performed, with a mean follow-up of 20 (range 12 to 38) months. Age, sex, incidence of fusion, interval to fusion, weightbearing status, and complication rates were evaluated. All subjects underwent Lapidus bunionectomy with joint preparation using sagittal planning. The fusion sites for group A fixation included a medially placed external fixation rail. Group B fixation included an interfragmentary screw and dorsal rail placement. Weightbearing was allowed in group A on day 1 and in group B on day 14. Our patient population consisted of 19 females (76%) and 6 males (24%). The mean patient age was 45.6 (range 28 to 63) years. The overall incidence of fusion was 96% (24 of 25), with complete union, although 1 patient's union was delayed. The mean interval to union for group A was 7.6 (range 6 to 8) weeks and for group B, was 9 (range 8 to 13) weeks. The primary complication encountered was pin tract infection in 11 patients (44%). The use of rail external fixation for Lapidus bunionectomy using either of the outlined techniques resulted in significant reduction of previously reported complication rates and allowed for early weightbearing. PMID- 25128309 TI - Infectious Spondylodiscitis, Epidural Phlegmon, and Psoas Abscess Complicating Diabetic Foot Infection: A Case Report. AB - Few published case reports have cited vertebral osteomyelitis as a sequela of a diabetic foot infection. The purpose of the present report is to increase awareness of a potentially severe complication of diabetic foot ulceration: vertebral osteomyelitis and associated pathologic features. We present the case of a 63-year-old male with right calcaneal osteomyelitis who developed acute onset lower back pain with concomitant fever and chills. Magnetic resonance imaging revealed L4-L5 vertebral osteomyelitis, a T9-L1 epidural abscess, and a right psoas muscle abscess secondary to hematogenous seeding from the calcaneus. The patient underwent right partial calcanectomy, spinal and right psoas abscess incision and drainage, and direct lumbar interbody fusion of L4-L5 with a right iliac crest allograft. All bone, blood, and abscess cultures were positive for methicillin-resistant Staphylococcus aureus. After the surgery, the patient's pain resolved in his back and hip and he regained full right lower extremity function. The 1-year follow-up examination revealed that the patient had vertebral arthritis but was able to perform his activities of daily living with a walker and cane. It is important to recognize the potential complications of diabetic foot ulcerations and be aware of the identifying symptoms and treatment options for this condition to prevent significant morbidity and mortality. PMID- 25128310 TI - Two different treatment options for intramuscular plantar hemangioma: surgery versus percutaneous sclerotherapy. AB - Intramuscular hemangiomas are benign neoplasms usually seen in children and adolescents. They tend to occur in the deep fascia and muscle and more often in the lower extremity, although they are rarely encountered in the plantar musculature. Surgical excision, ultrasound- or fluoroscopic-guided percutaneous sclerotherapy, and angiographic embolization are all treatment options. Surgical excision is the most prevalent form of therapy, although this can be difficult in the hands and feet. For this reason, ultrasound- and fluoroscopic-guided percutaneous sclerotherapy is a useful treatment option for pedal intramuscular hemangioma. In the present report, we describe 2 cases of intramuscular hemangioma in children, 1 treated by excision and 1 by percutaneous sclerosis. PMID- 25128311 TI - Management of Idiopathic Clubfoot by Ponseti Technique in Children Presenting After One Year of Age. AB - We conducted a study to determine the effectiveness of the Ponseti technique in the management of idiopathic congenital clubfoot in patients older than 1 year of age. A total of 19 patients with 28 clubfeet (16 males [84.2%], 3 females [15.8%]) were included in the present study. The mean age at presentation was 2.7 (range 1 to 3.5) years. The results of treatment using the Ponseti technique were evaluated using the Pirani and Dimeglio scoring systems. The mean precorrection total Pirani score was 4.84 (range 3.5 to 5.5) and the mean precorrection Dimeglio score was 12.96 (range 10 to 14). The mean postcorrection total Pirani score was 0.55 (range 0 to 1), and the mean postcorrection Dimeglio score was 2.32 (range 2 to 3). These differences were statistically significant (p < .001 and p < .001, respectively). In 92.8% of the feet, satisfactory correction of the deformity was achieved. The mean number of casts applied was 8 (range 5 to 12). All but 1 (3.6%) of the clubfeet required tenotomy to achieve correction. The mean follow-up duration was 2.7 (range 1.5 to 3.5) years. We have concluded that the Ponseti technique is an effective method for the management of idiopathic congenital clubfoot, even in toddlers. PMID- 25128312 TI - Tillaux fracture of the ankle in an adult: a rare injury. AB - The Tillaux fracture of the ankle is an external rotation ankle injury resulting in an avulsion fracture of the anterolateral tibial plafond. This injury is known to occur in adolescents, although it has rarely been reported in adults. We report a case of a Tillaux fracture in an adult. A brief description of the history, mechanism of injury, required imaging, and treatment and other management options are provided in the present report. Anatomic reduction, rigid fixation, and early mobilization are emphasized to obtain a satisfactory functional outcome, shown by the long-term follow-up findings. PMID- 25128313 TI - Treatment of Calcaneal Fracture With Severe Soft Tissue Injury and Osteomyelitis: A Case Report. AB - Advancements in surgical technique have resulted in the ability to reconstruct lower extremity injuries that would have previously been treated by amputation. Currently, a paucity of data is available specifically addressing limb amputation versus reconstruction for calcaneal fractures with severe soft tissue compromise. Reconstruction leaves the patient with their native limb; however, multiple surgeries, infections, chronic pain, and a poor functional outcome are very real possibilities. We present the case of a complex calcaneal fracture complicated by soft tissue injury and osteomyelitis that highlights the importance of shared decision-making between patient and surgeon when considering reconstruction versus amputation. This case exemplifies the need for open communication concerning the risks and benefits of treatment modalities while simultaneously considering the patient's expectations and desired outcomes. PMID- 25128314 TI - Application of the five stages of grief to diabetic limb loss and amputation. AB - A potentially underappreciated member of the multidisciplinary approach to diabetic limb salvage is that of psychiatry. Diabetic patients are more likely to experience depression, and diabetic patients with depression are more likely to undergo an amputation. Also, both diabetes and depression independently increase the healthcare costs in the United States. The objective of the present investigation was to increase knowledge among diabetic foot practitioners with respect to psychiatric and other mental health patient-care issues, specifically the potential application of the 5 stages of grief to diabetic limb loss and amputation. We enlisted the assistance of a clinical professor from the psychiatry department at our institution to review the 5 stages of grief, provide context specific for application to diabetic limb loss, and offer clinically relevant guidelines for surgeons to better understand and communicate with their patients at each stage. The 5 stages reviewed were denial, anger, bargaining, depression, and acceptance. We hope that the present review will increase the body of knowledge with respect to relevant psychiatric issues and the diabetic foot and provide a starting point for increased awareness with respect to this important, yet underappreciated, aspect of patient care. PMID- 25128315 TI - Symptomatic Osseous Abnormalities at the Posteromedial Tubercle of the Talus: Magnetic Resonance Imaging Features. AB - Osseous alterations adjacent to the posteromedial tubercle of the talus that lead to posterior ankle impingement and their imaging findings have been much less well described than alterations of the posterolateral tubercle. We present 5 cases of osseous abnormalities at the posteromedial tubercle of the talus depicted on magnetic resonance imaging in subjects with chronic symptoms at this location, with no history of local trauma, who had presented with posteromedial mechanical pain and/or tarsal tunnel syndrome. The symptoms were related to mechanical changes of the bony and soft tissue structures, leading to posterior impingement, and to neurovascular bundle entrapment at the tarsal tunnel, leading to tarsal tunnel syndrome. PMID- 25128316 TI - Multiple interdigital neuromas: a retrospective study of 279 feet with 462 neuromas. AB - Morton's neuroma is a common pathologic entity that, traditionally, was considered to be an isolated tumor that rarely affected more than 1 interdigital space. However, in recent years, multiple neuromas have become more common in our day-to-day practice. The objective of the present study was to assess the frequency with which Morton's neuroma appears in the different interdigital spaces. A retrospective study was performed of 279 feet that had been surgically treated for Morton's neuroma using a dorsal approach during a 9-year period (from January 2003 to December 2011), with an ultrasound scan taken preoperatively and histopathologic analysis performed afterward. From the 279 treated feet, 462 interdigital neuromas were surgically removed. Of the 279 feet, 97 (34.8%) displayed isolated neuromas, and 182 (65.2%) were treated for multiple neuromas. Regarding the neuromas that were treated as isolated lesions, 74.2% were located in the third space. For the feet affected by multiple interdigital neuromas, 100% had a neuroma in the third space and 98.9% in the second. The incidence of multiple interdigital neuromas can be considered frequent. The assessment, therefore, of interdigital neuromas of the foot should include, at a minimum, the second and third interdigital spaces. PMID- 25128317 TI - Effective connectivity at synaptic level in humans: a review and future prospects. AB - Correct knowledge of the effective connectivity at the synaptic level in humans is a key prerequisite for increasing our understanding of the operation of the human central nervous system. Unfortunately, none of the current ambitious collaborative neuroscience projects pay enough attention to this topic and are thus unable to completely relate the microlevel properties of the system to its emergent macrolevel behaviors. In this review article, the problem of effective connectivity at the synaptic level in humans is explained, existing and possible computational approaches to fill explanatory gaps are reviewed, and the requisite characteristics of these approaches are considered. PMID- 25128319 TI - Crista egregia: a geometrical model of the crista ampullaris, a sensory surface that detects head rotations. AB - The crista ampullaris is the epithelium at the end of the semicircular canals in the inner ear of vertebrates, which contains the sensory cells involved in the transduction of the rotational head movements into neuronal activity. The crista surface has the form of a saddle, or a pair of saddles separated by a crux, depending on the species and the canal considered. In birds, it was described as a catenoid by Landolt et al. (J Comp Neurol 159(2):257-287, doi: 10.1002/cne.901590207 , 1972). In the present work, we establish that this particular form results from principles of invariance maximization and energy minimization. The formulation of the invariance principle was inspired by Takumida (Biol Sci Space 15(4):356-358, 2001). More precisely, we suppose that in functional conditions, the equations of linear elasticity are valid, and we assume that in a certain domain of the cupula, in proximity of the crista surface, (1) the stress tensor of the deformed cupula is invariant under the gradient of the pressure, (2) the dissipation of energy is minimum. Then, we deduce that in this domain the crista surface is a minimal surface and that it must be either a planar, or helicoidal Scherk surface, or a piece of catenoid, which is the unique minimal surface of revolution. If we add the hypothesis that the direction of invariance of the stress tensor is unique and that a bilateral symmetry of the crista exists, only the catenoid subsists. This finding has important consequences for further functional modeling of the role of the vestibular system in head motion detection and spatial orientation. PMID- 25128320 TI - Torque-stiffness-controlled dynamic walking with central pattern generators. AB - Walking behavior is modulated by controlling joint torques in most existing passivity-based bipeds. Controlled Passive Walking with adaptable stiffness exhibits controllable natural motions and energy efficient gaits. In this paper, we propose torque-stiffness-controlled dynamic bipedal walking, which extends the concept of Controlled Passive Walking by introducing structured control parameters and a bio-inspired control method with central pattern generators. The proposed walking paradigm is beneficial in clarifying the respective effects of the external actuation and the internal natural dynamics. We present a seven-link biped model to validate the presented walking. Effects of joint torque and joint stiffness on gait selection, walking performance and walking pattern transitions are studied in simulations. The work in this paper develops a new solution of motion control of bipedal robots with adaptable stiffness and provides insights of efficient and sophisticated walking gaits of humans. PMID- 25128318 TI - Active inference, eye movements and oculomotor delays. AB - This paper considers the problem of sensorimotor delays in the optimal control of (smooth) eye movements under uncertainty. Specifically, we consider delays in the visuo-oculomotor loop and their implications for active inference. Active inference uses a generalisation of Kalman filtering to provide Bayes optimal estimates of hidden states and action in generalised coordinates of motion. Representing hidden states in generalised coordinates provides a simple way of compensating for both sensory and oculomotor delays. The efficacy of this scheme is illustrated using neuronal simulations of pursuit initiation responses, with and without compensation. We then consider an extension of the generative model to simulate smooth pursuit eye movements-in which the visuo-oculomotor system believes both the target and its centre of gaze are attracted to a (hidden) point moving in the visual field. Finally, the generative model is equipped with a hierarchical structure, so that it can recognise and remember unseen (occluded) trajectories and emit anticipatory responses. These simulations speak to a straightforward and neurobiologically plausible solution to the generic problem of integrating information from different sources with different temporal delays and the particular difficulties encountered when a system-like the oculomotor system-tries to control its environment with delayed signals. PMID- 25128321 TI - Effect of display resolution on time to diagnosis with virtual pathology slides in a systematic search task. AB - Performing diagnoses using virtual slides can take pathologists significantly longer than with glass slides, presenting a significant barrier to the use of virtual slides in routine practice. Given the benefits in pathology workflow efficiency and safety that virtual slides promise, it is important to understand reasons for this difference and identify opportunities for improvement. The effect of display resolution on time to diagnosis with virtual slides has not previously been explored. The aim of this study was to assess the effect of display resolution on time to diagnosis with virtual slides. Nine pathologists participated in a counterbalanced crossover study, viewing axillary lymph node slides on a microscope, a 23-in 2.3-megapixel single-screen display and a three screen 11-megapixel display consisting of three 27-in displays. Time to diagnosis and time to first target were faster on the microscope than on the single and three-screen displays. There was no significant difference between the microscope and the three-screen display in time to first target, while the time taken on the single-screen display was significantly higher than that on the microscope. The results suggest that a digital pathology workstation with an increased number of pixels may make it easier to identify where cancer is located in the initial slide overview, enabling quick location of diagnostically relevant regions of interest. However, when a comprehensive, detailed search of a slide has to be made, increased resolution may not offer any additional benefit. PMID- 25128323 TI - Health needs and neighbourhood concerns of low income households vulnerable to food insecurity. PMID- 25128322 TI - Infusion of Gabralpha6 siRNA into the trigeminal ganglia increased the myogenic orofacial nociceptive response of ovariectomized rats treated with 17beta estradiol. AB - High levels of 17beta-estradiol (E2) have been found to reduce inflammatory temporomandibular joint (TMJ) pain. A search for genes effected by a high concentration of estradiol showed an increase in GABAA receptor subunit alpha 6 (Gabralpha6) in the trigeminal ganglia (TG). Blockade of Gabralpha6 expression in the TG increases masseter muscle nociception in male rats, but the relationship between estradiol's effect on nociception and Gabralpha6 expression remains unclear in females. To address this knowledge gap we hypothesized that reducing Gabralpha6 expression in the TG will increase the orofacial nociceptive response of ovariectomized female rats treated with estradiol. To administer hormone osmotic pumps were placed in rats that dispensed a low diestrus plasma concentration of 17beta-estradiol, in addition, 17beta-estradiol was injected to produce a high proestrus plasma concentration of estradiol. A ligature was then placed around the masseter tendon to induce a nociceptive response; a model for TMJ muscle pain. Gabralpha6 small interfering RNA (siRNA) was later infused into the TG and the nociceptive response was measured using von Frey filaments and a meal duration assay. GABAA receptor expression was measured in the TG and trigeminal nucleus caudalis and upper cervical region (Vc-C1). Ligature significantly increased the nociceptive response but a high proestrus concentration of 17beta-estradiol attenuated this response. Gabralpha6 siRNA infusion decreased Gabralpha6 expression in the TG and Vc-C1 but increased the nociceptive response after 17beta-estradiol treatment. The results suggest estradiol decreased the orofacial nociceptive response, in part, by causing an increase in Gabralpha6 expression. PMID- 25128325 TI - Calcium in the heart: from physiology to disease. AB - Contraction of the heart results from an increase of cytoplasmic Ca(2+) concentration ([Ca(2+)]i), the so-called systolic Ca(2+) transient. Most of this results from the release of Ca(2+) from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR). In turn, the amplitude of this Ca(2+) transient determines the contractility of the heart. In this lecture, I consider the factors which govern the size and stability of this Ca(2+) release. The amplitude of the Ca(2+) transient is a steep function of SR Ca, resulting in a requirement for very precise beat-to-beat regulation of SR Ca content. This is achieved by a simple negative feedback mechanism, in which an increase of SR Ca content increases the size of the Ca(2+) transient, resulting in a decrease of Ca(2+) influx on the L-type Ca(2+) current and an increase of efflux through Na(+) Ca(2+) exchange. Changing the activity of any of the Ca(2+)-cycling proteins will change the steady-state SR Ca content. This feedback mechanism has many consequences, including the fact that a change of RyR open probability has a only a temporary effect on the amplitude of the Ca(2+) transient due to a compensating change of SR Ca content. The remainder of the article considers the link between intracellular Ca(2+) waves and arrhythmias. This is done in the context of catecholaminergic polymorphic ventricular tachycardia, which is an inherited arrhythmia syndrome, in many cases due to a RyR mutation, where arrhythmias occur during exercise as a result of beta-adrenergic stimulation. Calcium waves occur only when the SR Ca content exceeds a threshold level. Our data show that the threshold is reduced by the RyR mutation and that the adrenergic stimulation increases SR Ca content. PMID- 25128324 TI - Prevention of diabetes and cardiovascular diseases in occupational health care: feasibility and effectiveness. AB - AIMS: To evaluate feasibility and effectiveness of lifestyle counseling in occupational setting on decreasing risk for diabetes and cardiovascular disease. METHODS: A health check-up including physical examination, blood tests, questionnaires and health advice was completed on 2312 employees of an airline company. Participants with elevated risk for type 2 diabetes based on FINDRISC score and/or blood glucose measurement (n=657) were offered 1-3 additional lifestyle counseling sessions and 53% of them agreed to participate. After 2.5 years, 1347 employees of 2199 invited participated in a follow-up study. RESULTS: Among women and men with low baseline diabetes risk, cardiovascular risk factors increased slightly during follow-up. Larger proportion of the men who attended interventions lost weight at least 5% compared with the non-attendees (18.4% vs. 8.4%, p=0.031) and their FINDRISC score increased less (0.6 vs. 1.5, p=0.037). Older age associated with participation in follow-up and higher baseline FINDRISC score and presence of clinical and lifestyle risk factors and problems in sleep and mood increased attendance in interventions. CONCLUSIONS: Identification of employees with cardiovascular and diabetes risk, and the low intensity lifestyle intervention were feasible in occupational health-care setting. However, the health benefits were modest and observed only for men with increased risk. PMID- 25128326 TI - Mitochondrial function/dysfunction in white adipose tissue. AB - The role of mitochondria in white adipocytes has long been neglected due in part to their lower abundance in these cells. However, accumulating evidence suggests that mitochondria are vital for maintaining metabolic homeostasis in white adipocytes because of their involvement in adipogenesis, fatty acid synthesis and esterification, branched-chain amino acid catabolism and lipolysis. It is therefore not surprising that white adipose tissue function can be perturbed by altering mitochondrial components or oxidative capacity. Moreover, studies in humans and animals with significantly altered fat mass, such as in obesity or lipoatrophy, indicate that impaired mitochondrial function in adipocytes may be linked directly to the development of metabolic diseases such as diabetes and insulin resistance. However, recent studies that specifically targeted mitochondrial function in adipocytes indicated dissociation between impaired mitochondrial oxidative capacity and systemic insulin sensitivity. PMID- 25128327 TI - Erythropoietin administration alone or in combination with endurance training affects neither skeletal muscle morphology nor angiogenesis in healthy young men. AB - The aim was to investigate the ability of an erythropoiesis-stimulating agent (ESA), alone or in combination with endurance training, to induce changes in human skeletal muscle fibre and vascular morphology. In a comparative study, 36 healthy untrained men were randomly dispersed into the following four groups: sedentary-placebo (SP, n = 9); sedentary-ESA (SE, n = 9); training-placebo (TP, n = 10); or training-ESA (TE, n = 8). The ESA or placebo was injected once weekly. Training consisted of progressive bicycling three times per week for 10 weeks. Before and after the intervention period, muscle biopsies and magnetic resonance images were collected from the thigh muscles, blood was collected, body composition measured and endurance exercise performance evaluated. The ESA treatment (SE and TE) led to elevated haematocrit, and both ESA treatment and training (SE, TP and TE) increased maximal O2 uptake. With regard to skeletal muscle morphology, TP alone exhibited increases in whole-muscle cross-sectional area and fibre diameter of all fibre types. Also exclusively for TP was an increase in type IIa fibres and a corresponding decrease in type IIx fibres. Furthermore, an overall training effect (TP and TE) was statistically demonstrated in whole-muscle cross-sectional area, muscle fibre diameter and type IIa and type IIx fibre distribution. With regard to muscle vascular morphology, TP and TE both promoted a rise in capillary to muscle fibre ratio, with no differences between the two groups. There were no effects of ESA treatment on any of the muscle morphological parameters. Despite the haematopoietic effects of ESA, we provide novel evidence that endurance training rather than ESA treatment induces adaptational changes in angiogenesis and muscle morphology. PMID- 25128328 TI - Desire thinking: what is it and what drives it? AB - INTRODUCTION: The aim of this study was to provide an overview of the construct of desire thinking and test a metacognitive model of desire thinking and craving, based on the work of Spada, Caselli and Wells (2012; 2013), which aims to explain the perseveration of desire thinking. METHOD: We conducted two studies involving four clinical samples (total N = 493) and a community sample (N = 494) presenting with different addictive behaviors. The relationships among variables were examined by testing the fit of path models within each sample. RESULTS: In the model presented it was proposed that positive metacognitions about desire thinking are associated with, in turn, imaginal prefiguration and verbal perseveration, marking the activation of desire thinking. Verbal perseveration is then associated to negative metacognitions about desire thinking and craving denoting the pathological escalation of desire thinking. Finally, a direct association between positive metacognitions about desire thinking and negative metacognitions about desire thinking would mark those occasions where target achieving behaviour runs as an automatized schemata without the experience of craving. Results indicated a good model fit in the clinical sample and a variation in the model structure in the community sample. CONCLUSION: These findings provide further support for the application of metacognitive theory to desire thinking and craving in addictive behaviors. PMID- 25128329 TI - OX26/CTX-conjugated PEGylated liposome as a dual-targeting gene delivery system for brain glioma. AB - BACKGROUND: The successful gene delivery into the brain is a major challenge due to the presence of the blood-brain barrier (BBB). In order to transport plasmid DNA across the BBB and target the brain glioma, the PEGylated liposomes (PLs) modified with OX26 and chlorotoxin (CTX) were developed as a dual-targeting gene delivery system, and the therapeutic efficacy of OX26/CTX-PL/pC27 against glioma was evaluated using in vitro and in vivo experimental models. METHODS: The PEGylated liposome complexes were prepared by the reverse phase evaporation method, and their physicochemical properties were examined. The transfection efficiency, intracellular distribution, in vitro effects of OX26/CTX-PL/pC27 were determined on C6, F98 and HEK293T cell lines. The dual-targeting therapeutic efficacy of OX26/CTX-PL/pC27 against glioma were assessed using the BMVECs/C6 cells co-culture model and the rat orthotopic glioma model. RESULTS: The OX26/CTX PL/pDNA complexes exhibited a subglobose shape, and possessed notably low toxicities to HEK293T and C6 cells post 4 h incubation. In the in vitro transfection experiment, gene expressions of hTERTC27 from C6 and F98 cells were significantly improved by OX26 and CTX modification. Our in vitro results also showed that OX26 endowed the PLs with the transport ability across the BBB. Using the BMVECs/C6 cells co-culture model, the viability of C6 cells was decreased to 46.0% after OX26/CTX-PL/pC27 transfection. The OX26/CTX-PL/pC27 complexes exhibited enhanced therapeutic effects on C6 cells. Moreover, the dual-targeting therapeutic effects were further conformed with diminished tumor volumes (18.81 +/- 6.15 mm3) and extended median survival time (46 days) in C6 glioma-bearing rats. Immunohistochemical analysis revealed the therapeutic effects derived from enhanced hTERTC27 expression in the tumor site. CONCLUSIONS: The PEGylated liposomes modified with OX26 and CTX are able to significantly promote cell transfection, increase the transport of plasmid DNA across the BBB and afterwards target the brain glioma cells in vitro and in vivo, exhibit the most significant therapeutic efficacy. The ligand OX26 plays a critical role in transporting the lipoplexes across the BBB, and CTX acts as a major role in targeting brain glioma cells. The results would encourage further developments for non-invasive targeting therapy of brain gliomas by intravenous injection. PMID- 25128330 TI - Examining the use of evidence-based and social media supported tools in freely accessible physical activity intervention websites. AB - BACKGROUND: It has been shown that physical activity is more likely to increase if web-based interventions apply evidence-based components (e.g. self-monitoring) and incorporate interactive social media applications (e.g. social networking), but it is unclear to what extent these are being utilized in the publicly available web-based physical activity interventions. The purpose of this study was to evaluate whether freely accessible websites delivering physical activity interventions use evidence-based behavior change techniques and provide social media applications. METHODS: In 2013, a systematic search strategy examined 750 websites. Data was extracted on a wide range of variables (e.g. self-monitoring, goal setting, and social media applications). To evaluate website quality a new tool, comprising three sub-scores (Behavioral Components, Interactivity and User Generated Content), was developed to assess implementation of behavior change techniques and social media applications. An overall website quality scored was obtained by summing the three sub-scores. RESULTS: Forty-six publicly available websites were included in the study. The use of self-monitoring (54.3%), goal setting (41.3%) and provision of feedback (46%) was relatively low given the amount of evidence supporting these features. Whereas the presence of features allowing users to generate content (73.9%), and social media components (Facebook (65.2%), Twitter (47.8%), YouTube (48.7%), smartphone applications (34.8%)) was relatively high considering their innovative and untested nature. Nearly all websites applied some behavioral and social media applications. The average Behavioral Components score was 3.45 (+/-2.53) out of 10. The average Interactivity score was 3.57 (+/-2.16) out of 10. The average User Generated Content Score was 4.02 (+/-2.77) out of 10. The average overall website quality score was 11.04 (+/-6.92) out of 30. Four websites (8.7%) were classified as high quality, 12 websites (26.1%) were classified as moderate quality, and 30 websites (65.2%) were classified as low quality. CONCLUSIONS: Despite large developments in Internet technology and growth in the knowledge of how to develop more effective web-based interventions, overall website quality was low and the majority of freely available physical activity websites lack the components associated with behavior change. However, the results show that website quality can be improved by taking a number of simple steps, and the presence of social media applications in most websites is encouraging. PMID- 25128331 TI - Open drug scenes: responses of five European cities. AB - BACKGROUND: Open drug scenes are gatherings of drug users who publicly consume and deal drugs. The authors conducted a study of five European cities that have met such scenes constructively. The aim was to investigate shared and non-shared interventions and strategies in order to increase the understanding of this type of problem. METHODS: First a description was made for the cities of Amsterdam, Frankfurt, Vienna, Zurich and Lisbon. These descriptions were sent to contact persons in each city prior to visit by the researchers. The methods and strategies in each city were discussed and core choices and efforts extracted. A report was sent to the contact group for corrections and clarifications. The paper analyses shared and non-shared traits and strategies. RESULTS: All of the cities had initially a period with conflict between liberal and restrictive policies. A political consensus seems to be a prerequisite for effective action. A core shared characteristic was that drug dependence was met as a health problem and drug use behaviour as a public nuisance problem. Low threshold health services including opioid maintenance treatment were combined with outreach social work and effective policing. CONCLUSION: Prevention, harm reduction and treatment should be combined with law enforcement based on cooperation between police, health care and social services. The aim should be "coexistence" between society and users of illegal substances and the strategy based on several years planning and conjoint efforts. The solutions are found in appropriate combinations of harm reduction and restrictive measures. PMID- 25128332 TI - Community engagement and knowledge translation: progress and challenge in autism research. AB - The last decade has seen significant growth in scientific understanding and public awareness of autism. There is still a long road ahead before this awareness can be matched with parallel improvements in evidence-based practice. The process of translating evidence into community care has been hampered by the seeming disconnect between the mainstream scientific research agenda and the immediate priorities of many communities. The need for community engagement in the process of translating knowledge into impact has been recognized. However, there remains little consensus or empirical data regarding the process of such engagement and how to measure its impact. We shed light on a number of engagement models and tools, previously advocated in health research, as they apply to autism research. Furthermore, we illustrate the utility of such tools in supporting identification of knowledge gaps and priorities, using two community based case studies. The case studies illustrate that information generated from research is indeed relevant and critical for knowledge users in the community. Simple and systematic methods can support the translation and uptake of knowledge in diverse communities, therefore enhancing engagement with research and bridging research findings with immediate community needs. PMID- 25128333 TI - The pattern of hominin postcranial evolution reconsidered in light of size related shape variation of the distal humerus. AB - Previous research suggests that some hominin postcranial features do not follow a linear path of increasing modernization through geological time. With respect to the distal humerus, in particular, the earliest known hominin specimens are reportedly among the most modern in morphology, while some later humeri appear further removed from the average modern human shape. Although Plio-Pleistocene humeri vary widely in size, previous studies have failed to account for size related shape variation when making morphometric comparisons. This study reexamines hominin postcranial evolution in light of distal humeral allometry. Using two-dimensional landmark data, the relationship between specimen size and shape among modern humans is quantified using multivariate regression and principal components analysis of size-shape space. Fossils are compared with modern human shapes expected at a given size, as well as with the overall average human shape. The null hypothesis of humeral isometry in modern humans is rejected. Subsequently, if one takes allometry into account, the apparent pattern of hominin humeral evolution does not resemble the pattern described above. All 14 of the Plio-Pleistocene hominin fossils examined here share a similar pattern of shape differences from equivalently-sized modern humans, though they vary in the extent to which these differences are expressed. The oldest specimen in the sample (KNM-KP 271; Australopithecus anamensis) exhibits the least human-like elbow morphology. Similarly primitive morphology characterizes all younger species of Australopithecus as well as Paranthropus robustus. After 2 Ma, a subtly more human-like elbow morphology is apparent among specimens attributed to early Homo, as well as among isolated specimens that may represent either Homo or Paranthropus boisei. This study emphasizes the need to consider size-related shape variation when individual fossil specimens are compared with the average shape of a comparative group, particularly when specimens fall near an extreme of the comparative size distribution. PMID- 25128334 TI - A Leslie matrix model for Sicyopterus lagocephalus in La Reunion: sensitivity, uncertainty and research prioritization. AB - We propose a Leslie matrix model for the population dynamics of Sicyopterus lagocephalus in La Reunion. In order to capture both the amphidromous and the seasonal natures of the species' life history the model has four stages (sea+three river sites) and is cyclical with a 12 month period. Baseline parameters (age-specific fecundity, spatial dispersion patterns and survival rates) were chosen in such a way that the dominant eigenvalue of the year-on-year projection matrix is 1. Large uncertainties on the parameter values preclude the use of the model for management purpose. A sensitivity/uncertainty analysis sheds light on the parameters that cause much of the output to vary and that are poorly known: the life expectancy in rivers and the mortality both at river mouths and during the drift of larvae to sea. The aim is to help policymakers and researchers prioritize data acquisition efforts. The ultimate goal is a sustainable management of Sicyopterus lagocephalus in La Reunion. PMID- 25128335 TI - Services for Enhanced Recovery with Intensive and Continued Engagement (SERWICE): an outpatient psychiatric rehabilitation model from India. PMID- 25128336 TI - Global Summit on Regulatory Science 2013. AB - Regulatory science has been defined as the science that is used to develop regulatory decisions by government bodies. Regulatory science encompasses many scientific disciplines that oversee many studies producing a wide array of data. These may include fundamental research into the cellular interaction or response to a particular chemical or substance, hazard-assessment and dose-response studies in animal species, neurophysiological or neurobehavioral studies, best practices for the generation and analysis of genomics data, bioinformatics approaches, and mathematical modeling of risk. The Global Summit on Regulatory Science is an international conference with a mission to explore emerging and innovative technologies, and provide a platform to enhance translation of basic science into regulatory applications. The Third Global Summit on Regulatory Science which focused on nanotechnology is discussed. PMID- 25128337 TI - Site-directed mutagenesis of the heterotrimeric killer toxin zymocin identifies residues required for early steps in toxin action. AB - Zymocin is a Kluyveromyces lactis protein toxin composed of alphabetagamma subunits encoded by the cytoplasmic virus-like element k1 and functions by alphabeta-assisted delivery of the anticodon nuclease (ACNase) gamma into target cells. The toxin binds to cells' chitin and exhibits chitinase activity in vitro that might be important during gamma import. Saccharomyces cerevisiae strains carrying k1-derived hybrid elements deficient in either alphabeta (k1ORF2) or gamma (k1ORF4) were generated. Loss of either gene abrogates toxicity, and unexpectedly, Orf2 secretion depends on Orf4 cosecretion. Functional zymocin assembly can be restored by nuclear expression of k1ORF2 or k1ORF4, providing an opportunity to conduct site-directed mutagenesis of holozymocin. Complementation required active site residues of alpha's chitinase domain and the sole cysteine residue of beta (Cys250). Since betagamma are reportedly disulfide linked, the requirement for the conserved gamma C231 was probed. Toxicity of intracellularly expressed gamma C231A indicated no major defect in ACNase activity, while complementation of k1DeltaORF4 by gamma C231A was lost, consistent with a role of beta C250 and gamma C231 in zymocin assembly. To test the capability of alphabeta to carry alternative cargos, the heterologous ACNase from Pichia acaciae (P. acaciae Orf2 [PaOrf2]) was expressed, along with its immunity gene, in k1DeltaORF4. While efficient secretion of PaOrf2 was detected, suppression of the k1DeltaORF4-derived k1Orf2 secretion defect was not observed. Thus, the dependency of k1Orf2 on k1Orf4 cosecretion needs to be overcome prior to studying alphabeta's capability to deliver other cargo proteins into target cells. PMID- 25128338 TI - Engineering of Pseudomonas taiwanensis VLB120 for constitutive solvent tolerance and increased specific styrene epoxidation activity. AB - The application of whole cells as biocatalysts is often limited by the toxicity of organic solvents, which constitute interesting substrates/products or can be used as a second phase for in situ product removal and as tools to control multistep biocatalysis. Solvent-tolerant bacteria, especially Pseudomonas strains, are proposed as promising hosts to overcome such limitations due to their inherent solvent tolerance mechanisms. However, potential industrial applications suffer from tedious, unproductive adaptation processes, phenotypic variability, and instable solvent-tolerant phenotypes. In this study, genes described to be involved in solvent tolerance were identified in Pseudomonas taiwanensis VLB120, and adaptive solvent tolerance was proven by cultivation in the presence of 1% (vol/vol) toluene. Deletion of ttgV, coding for the specific transcriptional repressor of solvent efflux pump TtgGHI gene expression, led to constitutively solvent-tolerant mutants of P. taiwanensis VLB120 and VLB120DeltaC. Interestingly, the increased amount of solvent efflux pumps enhanced not only growth in the presence of toluene and styrene but also the biocatalytic performance in terms of stereospecific styrene epoxidation, although proton-driven solvent efflux is expected to compete with the styrene monooxygenase for metabolic energy. Compared to that of the P. taiwanensis VLB120DeltaC parent strain, the maximum specific epoxidation activity of P. taiwanensis VLB120DeltaCDeltattgV doubled to 67 U/g of cells (dry weight). This study shows that solvent tolerance mechanisms, e.g., the solvent efflux pump TtgGHI, not only allow for growth in the presence of organic compounds but can also be used as tools to improve redox biocatalysis involving organic solvents. PMID- 25128339 TI - Silver resistance genes are overrepresented among Escherichia coli isolates with CTX-M production. AB - Members of the Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs) of the CTX-M type have disseminated rapidly in recent years and have become a threat to public health. In parallel with the CTX-M type expansion, the consumption and widespread use of silver-containing products has increased. To determine the carriage rates of silver resistance genes in different Escherichia coli populations, the presence of three silver resistance genes (silE, silP, and silS) and genes encoding CTX-M-, TEM-, and SHV-type enzymes were explored in E. coli isolates of human (n = 105) and avian (n = 111) origin. The antibiotic profiles were also determined. Isolates harboring CTX-M genes were further characterized, and phenotypic silver resistance was examined. The silE gene was present in 13 of the isolates. All of them were of human origin. Eleven of these isolates harbored ESBLs of the CTX-M type (P = 0.007), and eight of them were typed as CTX-M-15 and three as CTX-M-14. None of the silE-positive isolates was related to the O25b-ST131 clone, but 10 out of 13 belonged to the ST10 or ST58 complexes. Phenotypic silver resistance (silver nitrate MIC > 512 mg/liter) was observed after silver exposure in 12 of them, and a concomitant reduced susceptibility to piperacillin-tazobactam developed in three. In conclusion, 12% of the human E. coli isolates but none of the avian isolates harbored silver resistance genes. This indicates another route for or level of silver exposure for humans than that caused by common environmental contamination. Since silE positive isolates were significantly more often found in CTX-M-positive isolates, it is possible that silver may exert a selective pressure on CTX-M-producing E. coli isolates. PMID- 25128340 TI - Characterization of novel polycyclic aromatic hydrocarbon dioxygenases from the bacterial metagenomic DNA of a contaminated soil. AB - Ring-hydroxylating dioxygenases (RHDs) play a crucial role in the biodegradation of a range of aromatic hydrocarbons found on polluted sites, including polycyclic aromatic hydrocarbons (PAHs). Current knowledge on RHDs comes essentially from studies on culturable bacterial strains, while compelling evidence indicates that pollutant removal is mostly achieved by uncultured species. In this study, a combination of DNA-SIP labeling and metagenomic sequence analysis was implemented to investigate the metabolic potential of main PAH degraders on a polluted site. Following in situ labeling using [(13)C]phenanthrene, the labeled metagenomic DNA was isolated from soil and subjected to shotgun sequencing. Most annotated sequences were predicted to belong to Betaproteobacteria, especially Rhodocyclaceae and Burkholderiales, which is consistent with previous findings showing that main PAH degraders on this site were affiliated to these taxa. Based on metagenomic data, four RHD gene sets were amplified and cloned from soil DNA. For each set, PCR yielded multiple amplicons with sequences differing by up to 321 nucleotides (17%), reflecting the great genetic diversity prevailing in soil. RHDs were successfully overexpressed in Escherichia coli, but full activity required the coexpression of two electron carrier genes, also cloned from soil DNA. Remarkably, two RHDs exhibited much higher activity when associated with electron carriers from a sphingomonad. The four RHDs showed markedly different preferences for two- and three-ring PAHs but were poorly active on four-ring PAHs. Three RHDs preferentially hydroxylated phenanthrene on the C-1 and C-2 positions rather than on the C-3 and C-4 positions, suggesting that degradation occurred through an alternate pathway. PMID- 25128341 TI - Surveillance of viruses in wild fish populations in areas around the Gulf of Cadiz (South Atlantic Iberian Peninsula). AB - This report describes a viral epidemiological study of wild fish around the Gulf of Cadiz (southwestern Iberian Peninsula) and is focused on infectious pancreatic necrosis virus (IPNV), viral hemorrhagic septicemia virus (VHSV), and viral nervous necrosis virus (VNNV). One fish species (Chelon labrosus) was sampled inside the gulf, at the mouth of the San Pedro River. Another 29 were sampled, in three oceanographic campaigns, at sites around the Bay of Cadiz. The fish were processed individually and subjected to isolation in cell culture and molecular diagnosis. VHSV was not isolated from any species. Thirteen IPNV-type isolates were obtained from barracuda (Sphyraena sphyraena), axillary seabream (Pagellus acarne), common two-banded seabream (Diplodus vulgaris), common pandora (P. erythrinus), Senegal seabream (D. bellottii), and surmullet (Mullus surmuletus). Six VNNV isolates were obtained from axillary seabream, common pandora, black seabream (Spondyliosoma cantharus), red mullet (Mullet barbatus), Lusitanian toadfish (Halobatrachus didactylus), and tub gurnard (Chelidonichtys lucerna). In the river mouth, viruses were detected only after reamplification, obtaining prevalence percentages of IPNV and VNNV (44.4 and 63.0%, respectively) much higher than those observed in the oceanographic campaigns (25.7 and 19.6%, respectively). The opposite results were obtained in the case of VHSV after reamplification: 11.1% in the river mouth and 43.6% in the oceanic locations. Analyzing the results with respect to the proximity of the sampling sites to the coast, an anthropogenic influence on wild fish is suggested and discussed. The type of viruses and the presence of natural reassortants are also discussed. PMID- 25128342 TI - Incorporation of exogenous fatty acids protects Enterococcus faecalis from membrane-damaging agents. AB - Enterococcus faecalis is a commensal bacterium of the mammalian intestine that can persist in soil and aquatic systems and can be a nosocomial pathogen to humans. It employs multiple stress adaptation strategies in order to survive such a wide range of environments. Within this study, we sought to elucidate whether membrane fatty acid composition changes are an important component for stress adaptation. We noted that E. faecalis OG1RF was capable of changing its membrane composition depending upon growth phase and temperature. The organism also readily incorporated fatty acids from bile, serum, and medium supplemented with individual fatty acids, often dramatically changing the membrane composition such that a single fatty acid was predominant. Growth in either low levels of bile or specific individual fatty acids was found to protect the organism from membrane challenges such as high bile exposure. In particular, we observed that when grown in low levels of bile, serum, or the host-derived fatty acids oleic acid and linoleic acid, E. faecalis was better able to survive the antibiotic daptomycin. Interestingly, the degree of membrane saturation did not appear to be important for protection from the stressors examined here; instead, it appears that a specific fatty acid or combination of fatty acids is critical for stress resistance. PMID- 25128343 TI - Analysis of the xplAB-containing gene cluster involved in the bacterial degradation of the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine. AB - Repeated use of the explosive compound hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) on military land has resulted in significant soil and groundwater pollution. Rates of degradation of RDX in the environment are low, and accumulated RDX, which the U.S. Environmental Protection Agency has determined is a possible human carcinogen, is now threatening drinking water supplies. RDX degrading microorganisms have been isolated from RDX-contaminated land; however, despite the presence of these species in contaminated soils, RDX pollution persists. To further understand this problem, we studied RDX-degrading species belonging to four different genera (Rhodococcus, Microbacterium, Gordonia, and Williamsia) isolated from geographically distinct locations and established that the xplA and xplB (xplAB) genes, which encode a cytochrome P450 and a flavodoxin redox partner, respectively, are nearly identical in all these species. Together, the xplAB system catalyzes the reductive denitration of RDX and subsequent ring cleavage under aerobic and anaerobic conditions. In addition to xplAB, the Rhodococcus species studied here share a 14-kb region flanking xplAB; thus, it appears likely that the RDX-metabolizing ability was transferred as a genomic island within a transposable element. The conservation and transfer of xplAB flanking genes suggest a role in RDX metabolism. We therefore independently knocked out genes within this cluster in the RDX-degrading species Rhodococcus rhodochrous 11Y. Analysis of the resulting mutants revealed that XplA is essential for RDX degradation and that XplB is not the sole contributor of reducing equivalents to XplA. While XplA expression is induced under nitrogen limiting conditions and further enhanced by the presence of RDX, MarR is not regulated by RDX. PMID- 25128344 TI - Strain diversity of CTX-M-producing Enterobacteriaceae in individual pigs: insights into the dynamics of shedding during the production cycle. AB - The aim of this study was to evaluate the population dynamics of CTX-M-producing Enterobacteriaceae in individual pigs on a farm positive for CTX-M-14-producing Escherichia coli. Fecal samples were collected once around the farrowing time from five sows and four times along the production cycle from two of their respective offspring. Multiple colonies per sample were isolated on cefotaxime supplemented MacConkey agar with or without prior enrichment, resulting in 98 isolates identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and tested for blaCTX-M. CTX-M-positive isolates (n = 86) were typed by pulsed-field gel electrophoresis (PFGE). Plasmids harboring blaCTX-M were characterized in 22 representative isolates by replicon typing and restriction fragment length polymorphism. Based on the PFGE results, all individuals shed unrelated CTX-M-14-producing E. coli strains during the course of life. Concomitant shedding of CTX-M-2/97-producing Proteus mirabilis or Providencia rettgeri was observed in two sows and two offspring. At least two genetically unrelated CTX-M-producing E. coli strains were isolated from approximately one-fourth of the samples, with remarkable differences between isolates obtained by enrichment and direct plating. A clear decrease in strain diversity was observed after weaning. Dissemination of blaCTX-M-14 within the farm was attributed to horizontal transfer of an IncK plasmid that did not carry additional resistance genes and persisted in the absence of antimicrobial selective pressure. Assessment of strain diversity was shown to be influenced by the production stage from which samples were collected, as well as by the isolation method, providing useful information for the design and interpretation of future epidemiological studies of CTX-M-producing Enterobacteriaceae in pig farms. PMID- 25128345 TI - The two-component GacS-GacA system activates lipA translation by RsmE but not RsmA in Pseudomonas protegens Pf-5. AB - In Pseudomonas spp., the Gac-Rsm signal transduction system is required for the production of lipases. The current model assumes that the system induces lipase gene transcription mediated through the quorum-sensing (QS) system. However, there are no reports of a QS system based upon N-acyl homoserine lactones or the regulation of lipase gene expression in Pseudomonas protegens. In this study, we investigated the regulatory mechanism acting on lipA expression activated by the Gac-Rsm system in P. protegens Pf-5 through deletion and overexpression of gacA, overexpression of rsmA or rsmE, expression of various lacZ fusions, reverse transcription-PCR analysis, and determination of whole-cell lipase activity. The results demonstrated that the GacS-GacA (GacS/A) system activates lipA expression at both the transcriptional and the translational levels but that the translational level is the key regulatory pathway. Further results showed that the activation of lipA translation by the GacS/A system is mediated through RsmE, which inhibits lipA translation by binding to the ACAAGGAUGU sequence overlapping the Shine-Dalgarno (SD) sequence of lipA mRNA to hinder the access of the 30S ribosomal subunit to the SD sequence. Moreover, the GacS/A system promotes lipA transcription through the mediation of RsmA inhibiting lipA transcription via an unknown pathway. Besides the transcriptional repression, RsmA mainly activates lipA translation by negatively regulating rsmE translation. In summary, in P. protegens Pf-5, the Gac-RsmE system mainly and directly activates lipA translation and the Gac-RsmA system indirectly enhances lipA transcription. PMID- 25128346 TI - Microbial odor profile of polyester and cotton clothes after a fitness session. AB - Clothing textiles protect our human body against external factors. These textiles are not sterile and can harbor high bacterial counts as sweat and bacteria are transmitted from the skin. We investigated the microbial growth and odor development in cotton and synthetic clothing fabrics. T-shirts were collected from 26 healthy individuals after an intensive bicycle spinning session and incubated for 28 h before analysis. A trained odor panel determined significant differences between polyester versus cotton fabrics for the hedonic value, the intensity, and five qualitative odor characteristics. The polyester T-shirts smelled significantly less pleasant and more intense, compared to the cotton T shirts. A dissimilar bacterial growth was found in cotton versus synthetic clothing textiles. Micrococci were isolated in almost all synthetic shirts and were detected almost solely on synthetic shirts by means of denaturing gradient gel electrophoresis fingerprinting. A selective enrichment of micrococci in an in vitro growth experiment confirmed the presence of these species on polyester. Staphylococci were abundant on both cotton and synthetic fabrics. Corynebacteria were not enriched on any textile type. This research found that the composition of clothing fibers promotes differential growth of textile microbes and, as such, determines possible malodor generation. PMID- 25128348 TI - Is society being reshaped on a microbiological and epigenetic level by the way women give birth? PMID- 25128347 TI - Enhanced uranium immobilization and reduction by Geobacter sulfurreducens biofilms. AB - Biofilms formed by dissimilatory metal reducers are of interest to develop permeable biobarriers for the immobilization of soluble contaminants such as uranium. Here we show that biofilms of the model uranium-reducing bacterium Geobacter sulfurreducens immobilized substantially more U(VI) than planktonic cells and did so for longer periods of time, reductively precipitating it to a mononuclear U(IV) phase involving carbon ligands. The biofilms also tolerated high and otherwise toxic concentrations (up to 5 mM) of uranium, consistent with a respiratory strategy that also protected the cells from uranium toxicity. The enhanced ability of the biofilms to immobilize uranium correlated only partially with the biofilm biomass and thickness and depended greatly on the area of the biofilm exposed to the soluble contaminant. In contrast, uranium reduction depended on the expression of Geobacter conductive pili and, to a lesser extent, on the presence of the c cytochrome OmcZ in the biofilm matrix. The results support a model in which the electroactive biofilm matrix immobilizes and reduces the uranium in the top stratum. This mechanism prevents the permeation and mineralization of uranium in the cell envelope, thereby preserving essential cellular functions and enhancing the catalytic capacity of Geobacter cells to reduce uranium. Hence, the biofilms provide cells with a physically and chemically protected environment for the sustained immobilization and reduction of uranium that is of interest for the development of improved strategies for the in situ bioremediation of environments impacted by uranium contamination. PMID- 25128350 TI - Safety and tolerability of zonisamide in paediatric patients with epilepsy. AB - BACKGROUND: Zonisamide has recently been approved in Europe for the adjunctive treatment of partial seizures (with or without secondary generalisation) in adolescents and children aged >=6 years. AIM: To further assess the safety of adjunctive zonisamide in paediatric epilepsy patients. METHODS: A pooled analysis of data from 17 studies (including four randomised, double-blind trials) was conducted. The safety population comprised patients aged <=16 years receiving at least one dose of study drug. Assessments included treatment-emergent adverse events (TEAEs), clinical laboratory parameters, vital signs and electrocardiography. RESULTS: The analysis included 398 patients treated with zonisamide (<12 years, n = 191; 12-16 years, n = 207). All but seven patients received zonisamide as adjunctive therapy. Mean duration of exposure was 318.7 days (mean dose, 253.1 mg/day). Most TEAEs were of mild or moderate intensity. The most frequently reported treatment-related TEAEs were decreased appetite (15.6%), somnolence (12.1%), fatigue (9.3%), dizziness (6.0%), decreased weight (5.8%), irritability (5.8%) and headache (5.3%). Incidence of serious zonisamide related TEAEs was low (3.5% overall). TEAEs most commonly leading to discontinuation were lethargy (1.0%) and fatigue (1.0%). TEAEs of decreased weight and decreased appetite occurred in 28 (7.0%) and 78 (19.6%) patients, respectively. Twenty-eight patients had decreased bicarbonate levels, but there were no reports of respiratory alkalosis or metabolic acidosis. No changes in vital signs of clinical concern were observed and there were no reports of clinically significant electrocardiogram abnormalities with zonisamide treatment. CONCLUSION: Zonisamide demonstrated an acceptable safety profile when used as adjunctive treatment in paediatric patients. PMID- 25128349 TI - Comparison of NaF and FDG PET/CT for assessment of treatment response in castration-resistant prostate cancers with osseous metastases. AB - BACKGROUND: Assessment of skeletal metastases' response to therapy is a highly relevant but unresolved clinical problem. The main goal of this work was to compare pharmacodynamic responses to therapy assessed with positron emission tomography-computed tomography (PET/CT) using fluorine-18 sodium fluoride (NaF) and fluorine-18 fluorodeoxyglucose (FDG) as the tracers. MATERIALS AND METHODS: Patients with prostate cancer with known osseous metastases were treated with zibotentan (ZD4054) and imaged with combined dynamic NaF/FDG PET/CT before therapy (baseline), after 4 weeks of therapy (week 4), and after 2 weeks of treatment break (week 6). Kinetic analysis allowed comparison of the voxel-based tracer uptake rate parameter Ki, the vasculature parameters K1 (measuring perfusion/permeability) and Vb (measuring vasculature fraction in the tissue), and the standardized uptake values (SUVs). RESULTS: Correlations were high for the NaF and FDG peak uptake parameters (Ki and SUV correlations ranged from 0.57 to 0.88) and for vasculature parameters (K1 and Vb correlations ranged from 0.61 to 0.81). Correlation was low between the NaF and FDG week 4 Ki responses (rho = 0.35; P = .084) but was higher for NaF and FDG week 6 Ki responses (rho = 0.72; P < .0001). Correlations for vasculature responses were always low (rho < 0.35). NaF and FDG uptakes in the osseous metastases were spatially dislocated, with overlap in the range from 0% to 80%. CONCLUSION: This study found that late NaF and FDG uptake responses are consistently correlated but that earlier uptake responses and all vasculature responses can be unrelated. This study also confirmed that FDG and NaF uptakes are spatially dislocated. Although treatment responses assessed with NaF and FDG may be correlated, using both tracers provides additional information. PMID- 25128351 TI - Association of ICAM-1 K469E polymorphism with neurocysticercosis. AB - Neurocysticercosis (NCC), a central nervous system (CNS) disease is caused by the larval stage of Taenia solium. The disease is heterogeneous in clinical presentation; some infected individuals develop symptoms and others may remain symptom free. Impaired blood brain barrier allows recruitment of immune cells in the CNS during infection and soluble intercellular adhesion molecule-1 (sICAM-1) plays an important role in the recruitment of immune cells. We studied ICAM-1 K469E polymorphism among symptomatic and asymptomatic NCC patients. The study revealed that individuals with variant (EE) genotype were more susceptible to symptomatic NCC and also had an elevated level of sICAM-1. PMID- 25128352 TI - [Vision and evolution of patient safety in Catalonia]. PMID- 25128353 TI - [Epidemiology of the hospital adverse events in Catalonia, Spain: a first step for the patient safety improvement]. AB - It has been published that hospital adverse events are an important source of morbidity and mortality in different countries and settings. The aim of this study was to evaluate the frequency, magnitude, distribution and degree of preventability of adverse events in the Autonomous Community of Catalonia (Spain). We conducted a retrospective cohort study of 4,790 hospital discharges that were selected by simple random sampling after stratified multistage sampling in 15 hospitals in Catalonia. 38.25% of patients had positive risk criteria (screening phase). We identified 356 cases of adverse events, which represent a 7.4% (95%CI: 6.7% to 8.1%). Of these, 43.5% (155 cases) were considered preventable. This study confirms that adverse events in hospitals in Catalonia are frequent, and generate a significant impact on morbidity and mortality. As in other studies, corroborated that a high proportion of these adverse events are considered preventable. It was possible to identify priority areas to focus improvement efforts. PMID- 25128354 TI - [Results of the implementation of the Bacteremia Zero project in Catalonia, Spain]. AB - The nationwide Bacteremia Zero (BZ) Project consists in the simultaneous implementation of measures to prevent central venous catheter-related bacteremia (CVC-B) in critically ill patients and in the development of an integral safety plan. The objective is to present the results obtained after the implementation of the BZ project in the ICUs of the Autonomous Community of Catalonia, Spain. All patients admitted to ICUs in Catalonia participating in the ENVIN-HELICS registry between January 2009 and June 2010 were included. Information was provided by 36 (92.3%) of the total possible 39 ICUs. A total of 281 episodes of CVC-B were diagnosed (overall rate of 2.53 episodes per 1000 days of CVC). The rates have varied significantly between ICUs that participated in the project for more or less than 12 months (2.17 vs. 4.27 episodes per 1000 days of CVC, respectively; p<.0001). The implementation of the BZ Project in Catalonia has been associated with a decrease greater than 40% in the CVC-B rates in the ICUs of this community, which is much higher than the initial objective of 4 episodes per 1000 days of CVC). PMID- 25128355 TI - [A surgical safety checklist implementation: experience of a start-up phase of a collaborative project in hospitals of Catalonia, Spain]. AB - Surgical patient safety is a priority in the national and international quality healthcare improvement strategies. The objective of the study was to implement a collaborative intervention with multiple components and to evaluate the impact of the patient surgical safety checklist (SSC) application. This is a prospective, longitudinal multicenter study with a 7-month follow-up period in 2009 based on a collaborative intervention for the implementation of a 24 item-SSC distributed in 3 different stages (sign in, time out, sign out) for its application to the surgical patient. A total number of 27 hospitals participated in the strategy. The global implementation rate was 48% (95%CI, 47.6%-48.4%) during the evaluation period. The overall compliance with all the items of the SSC included in each stage (sign in, time out, sign out) was 75,1% (95%CI, 73.5%-76.7%) for the sign in, 77.1% (95%CI, 75.5%-78.6%) for the time out and 88.3% (95%CI, 87.2%-89.5%) for the sign out respectively. The individual compliance with each item of the SSC has remained above 85%, except for the surgical site marking with an adherence of 67.4% (95%CI, 65.7%-69.1%)] and 71.2% (95%CI, 69.6%-72.9%)] in the sign in and time out respectively. The SSC was successfully implemented to 48% of the surgeries performed to the participating hospitals. The global compliance with the SSC was elevated and the intervention trend was stable during the evaluation period. Strategies were identified to allow of a higher number of surgeries with application of the SSC and more professional involvement in measures compliance such as surgical site marking. PMID- 25128356 TI - [Study on the improvement of trauma patient care: TRAUMACAT project]. AB - Multiple injuries are a major source of morbidity and mortality in young people. The aim of this study was to evaluate the effect of a collaborative strategy to improve the implementation of six clinical indicators, recognized internationally, for the treatment of trauma patient. Prospective, multicentre, pre-and post-intervention study, in ten referral hospitals, offering polytrauma care in Catalonia. 378 patients were recruited for the pre-intervention study and 501 for the post-intervention study. All patients had a history of high-energy trauma requiring admission to critical or semi-critical care unit. INTERVENTION: collaborative strategy aimed at participating professionals, involving the creation of a panel of experts, appointment of monitors to encourage improvements at each centre, training, distribution of information, material and meetings, to exchange impressions. MAIN OUTCOME MEASURES: frequency and characteristics of trauma and percentage of compliance with clinical indicators. Study of 879 trauma patients. The injury mechanism was overall blunt trauma, in both pre and post intervention phases. The medium ISS (injury severity score) was 21 +/- 12,8 and the medium TRISS (trauma and injury severity score) was 26,4 +/- 11,4. We didn't find differences between both study phases, in relation to the severity of injury. The mortality rate was 11.5%. We observed significant improvement in the performance of chest X-rays (45% vs. 62%) and pelvis X-rays (27% vs. 62%) in the trauma box and in the fixation of the pelvis in patients with a fracture at this site (24% vs. 49%). The use of diagnostic radiology in hemodynamically unstable patients remained low (33%). The collaborative strategy was effective in improving certain indicators of clinical management. PMID- 25128357 TI - [Patient safety in primary care: PREFASEG project]. AB - The Institut Catala de la Salut (ICS) has designed and integrated in electronic clinical station of primary care a new software tool to support the prescription of drugs, which can detect on-line certain medication errors. The software called PREFASEG (stands for Secure drug prescriptions) aims to prevent adverse events related to medication use in the field of primary health care (PHC). This study was made on the computerized medical record called CPT, which is used by all PHC physicians in our institution -3,750- and prescribing physicians through it. PREFASEG integrated in eCAP in July 2010 and six months later we performed a cross-sectional study to evaluate their usefulness and refine their design. The software alerts on-line in 5 dimensions: drug interactions, redundant treatments, allergies, contraindications of drugs with disease, and advises against drugs in over 75 years. PREFASEG generated 1,162,765 alerts (1 per 10 high treatment), with the detection of therapeutic duplication (62%) the most alerted. The overall acceptance rate is 35%, redundancies pharmacological (43%) and allergies (26%) are the most accepted. A total of 10,808 professionals (doctors and nurses) have accepted some of the recommendations of the program. PREFASEG is a feasible and highly efficient strategy to achieve an objective of Quality Plan for the NHS. PMID- 25128358 TI - [Intervention to improve hand hygiene compliance in Catalonia, Spain]. AB - Hand hygiene (HM) is the single most important measure and effective in reducing the risk of Healthcare acquired infections (IRAS). Although HM is an effective, simple and cheap measure, it is usual to find results of low compliance among health professionals. The main objective of this strategy has been to give new force to the promotion of HM in hospitals and educate professionals about the importance of this single action. The strategy was planned as a multicenter intervention study to promote HM in health centers of Catalonia in 2009-2010. The intervention is based on 4 main areas: a survey of barriers and facilitators, distribution of graphic material, training at different levels and measure of quality indicators. With this strategy a total of 57% of the number of acute beds in the concerted public and private network of hospitals were reached. The survey revealed that training was perceived as the main facilitator of the HM action. 15,376 professionals registered to the on-line training. The overall compliance with HM indications (based on "five moments for HM") was 56.45% in the acute areas. The campaigns and programs to promote HM carried out in the last four years in Catalonia has helped to achieve an increasing number of hospitals associated to the strategy of the Alliance for Patient Safety in Catalonia. The on-line curse acceptance was very high and seems a powerful tool to improve hand hygiene knowledge and compliance among health professionals. The compliance of HM seems to increase in the hospitals of Catalonia evaluated. PMID- 25128359 TI - [Validation of the structure and resources of nosocomial infection control team in hospitals ascribed to VINCat program in Catalonia, Spain]. AB - The main objective of this study was to validate the structure of the infection control team (ICT) in the hospitals adhered to VINCat program and secondary objective was to establish the consistency of resources of each center with the requirements established by the program. Qualitative research consisting of an ethnographic study using participant observation during the years 2008-2010. The centers were stratified in three groups by complexity and beds. The instrument was a semistructured interview to members of the ICT. The transcription of the interview was sent to informants for validation. In November 2010 a questionnaire regarding human resources and number hours dedicated to the ICT was sent. During 2008-2010, 65 centers had been adhered to VINCat program. In 2010, the ICT of Group I hospitals had a mean of two physician, one in full-time and one nurse for every 230 beds. In Group II, one physician part-time and one nurse per 180 beds and in Group III a physician and a nurse for every 98 beds, both part-time. In 2010, all hospitals had a structured ICT, an operative infection committee, and a hospital member representing the center at the program as well as enough electronic resources. The hospitals participating in the program have now VINCat an adequate surveillance structure and meet the minimum technical and human resources required to provide high-quality data. However human resources are not guaranteed. PMID- 25128360 TI - [Design, implementation and evaluation of a management model of patient safety in hospitals in Catalonia, Spain]. AB - Since its inception in 2006, the Alliance for Patient Safety in Catalonia has played a major role in promoting and shaping a series of projects related to the strategy of the Ministry of Health, Social Services and Equality, for improving patient safety. One such project was the creation of functional units or committees of safety in hospitals in order to facilitate the management of patient safety. The strategy has been implemented in hospitals in Catalonia which were selected based on criteria of representativeness. The intervention was based on two lines of action, one to develop the model framework and the other for its development. Firstly the strategy for safety management based on EFQM (European Foundation for Quality Management) was defined with the development of standards, targets and indicators to implement security while the second part involved the introduction of tools, methodologies and knowledge to the management support of patient safety and risk prevention. The project was developed in four hospital areas considered higher risk, each assuming six goals for safety management. Some of these targets such as the security control panel or system of adverse event reporting were shared. 23 hospitals joined the project in Catalonia. Despite the different situations in each centre, high compliance was achieved in the development of the objectives. In each of the participating areas the security control panel was developed. Stable structures for safety management were established or strengthened. Training in patient safety played and important role, 1415 professionals participated. Through these kind of projects not only have been introduced programs of proven effectiveness in reducing risks, but they also provide to the facilities a work system that allows autonomy in diagnosis and analysis of the different risk situations or centre specific safety issues. PMID- 25128361 TI - [Notification of incidents related to patient safety in hospitals in Catalonia, Spain during the period 2010-2013]. AB - The aim of this paper is to discover the aggregated results of a general notification system for incidents related to patient safety implemented in Catalan hospitals from 2010 to 2013. Observational study describing the incidents notified from January 2010 to December 2013 from all hospitals in Catalonia forming part of the project to create operational patient safety management units. The Patient Safety Notification and Learning System (SiNASP) was used. This makes it possible to classify incidents depending on the area where they occur, the type of incident notified, the consequences, the seriousness according to the Severity Assessment Code (SAC) and the profession of the notifying party, as the principal variables. The system was accessed via the Internet (SiNASP portal). Access was voluntary and anonymous or with a name given and later removed. During the study period, notification of a total of 5,948 incidents came from 22-29 hospitals. 5,244 of the incidents were handled by the centres and these are the ones analysed in the study. 64% (3,380) affected patients, 18% (950) created a situation capable of causing an incident and 18% (914) did not affect patients. 26% of incidents that affected patients (864) caused some kind of harm. Most incidents occurred during hospitalisation (54%) and in casualty (15%), followed by the ICU (9%) and the surgical block (8%). The most frequent notifying parties were nurses (71%) followed by doctors (15%) and pharmacists (9%). In terms of severity, most incidents were classified as low-risk (37%) or incidents that did not affect the patient (36%). However, 40 cases (0.76%) of extreme risk should be highlighted. In terms of the types of incident notified, most were due to a medication error (26.8%), followed by falls (16.3%) and patient identification (10.6%). The majority of notifications were incidents that affected patients and, of these, 26% caused harm. In general, they occurred in hospitalisation units and notification was mostly given by nurses. The incident notification system is a tool that complements others for promoting a patient safety culture and defining the risk profile of a health organisation. The opportunity for learning from experience is the reason for the existence of the notification system. PMID- 25128362 TI - [Optimization of radiological scoliosis assessment]. AB - Most scoliosis are idiopathic (80%) and occur more frequently in adolescent girls. Plain radiography is the imaging method of choice, both for the initial study and follow-up studies but has the disadvantage of using ionizing radiation. The breasts are exposed to x-ray along these repeated examinations. The authors present a range of recommendations in order to optimize radiographic exam technique for both conventional and digital x-ray settings to prevent unnecessary patients' radiation exposure and to reduce the risk of breast cancer in patients with scoliosis. With analogue systems, leaded breast protectors should always be used, and with any radiographic equipment, analog or digital radiography, the examination should be performed in postero-anterior projection and optimized low dose techniques. The ALARA (as low as reasonable achievable) rule should always be followed to achieve diagnostic quality images with the lowest feasible dose. PMID- 25128363 TI - [Accreditation model for acute hospital care in Catalonia, Spain]. AB - The implementation of an accreditation model for healthcare centres in Catalonia which was launched for acute care hospitals, leaving open the possibility of implementing it in the rest of lines of service (mental health and addiction, social health, and primary healthcare centres) is described. The model is based on the experience acquired over more tan 31 years of hospital accreditation and quality assessment linked to management. In January 2006 a model with accreditation methodology adapted to the European Foundation for Quality Management (EFQM) model was launched. 83 hospitals are accredited, with an average of 82.6% compliance with the standards required for accreditation. The number of active assessment bodies is 5, and the accreditation period is 3 years. A higher degree of compliance of the so-called "agent" criteria with respect to "outcome" criteria is obtained. Qualitative aspects for implementation to be stressed are: a strong commitment both from managers and staff in the centres, as well as a direct and fluent communication between the accreditation body (Ministry of Health of the Government of Catalonia) and accredited centres. Professionalism of audit bodies and an optimal communication between audit bodies and accredited centres is also added. PMID- 25128364 TI - [Catalonia's primary healthcare accreditation model: a valid model]. AB - There are few experiences of accreditation models validated by primary care teams (EAP). The aim of this study was to detail the process of design, development, and subsequent validation of the consensus EAP accreditation model of Catalonia. An Operating Committee of the Health Department of Catalonia revised models proposed by the European Foundation for Quality Management, the Joint Commission International and the Institut Catala de la Salut and proposed 628 essential standards to the technical group (25 experts in primary care and quality of care), to establish consensus standards. The consensus document was piloted in 30 EAP for the purpose of validating the contents, testing standards and identifying evidence. Finally, we did a survey to assess acceptance and validation of the document. The Technical Group agreed on a total of 414 essential standards. The pilot selected a total of 379. Mean compliance with the standards of the final document in the 30 EAP was 70.4%. The standards results were the worst fulfilment percentage. The survey target that 83% of the EAP found it useful and 78% found the content of the accreditation manual suitable as a tool to assess the quality of the EAP, and identify opportunities for improvement. On the downside they highlighted its complexity and laboriousness. We have a model that fits the reality of the EAP, and covers all relevant issues for the functioning of an excellent EAP. The model developed in Catalonia is a model for easy understanding. PMID- 25128365 TI - Should we advise patients with lupus to quit smoking? PMID- 25128366 TI - Quantification of V(D)J recombination by real-time quantitative PCR. AB - B and T lymphocytes have the unique capacity to somatically rearrange their antigen receptor loci through V(D)J recombination. D-JH and VH-DJH recombination events are usually visualized by semi-quantitative PCR followed by detection of end products, which is time consuming and requires the use of hazardous elements. Additionally, it necessitates relatively large amounts of genomic DNA which could be limiting when the cell populations of interest are rare. Here, we describe a real-time quantitative PCR assay for a fast quantification of V(D)J recombination events at the IgH locus. PMID- 25128367 TI - Electrochemical performance and detection of 8-Hydroxy-2'-deoxyguanosine at single-stranded DNA functionalized graphene modified glassy carbon electrode. AB - 8-Hydroxy-2'-deoxyguanosine (8-OH-dG) is the most abundant oxidative product of DNA and it is also considered to be a biomarker of oxidative DNA damage. In this work, a novel biosensor was fabricated by combining the biocompatibility of single-stranded DNA (ss-DNA) and the excellent conductivity of graphene nanosheets (GNs). The biosensor showed high electrocatalytic activity to the oxidation of 8-OH-dG. The sensitivities were 13.23 (+/-0.03)MUA MUM(-1), 5.827 (+/-0.008) MUA MUM(-1) and 3.086 (+/-0.005) MUA MUM(-1) in the concentration ranges of 0.0056-1.155 MUM, 1.155-11.655 MUM and 11.655-36.155 MUM, respectively. The detection limit was 0.875 nM (S/N=3). Furthermore, the electrochemical behavior of 8-OH-dG was also investigated in detail in the presence of uric acid. And the results showed that uric acid had interference with the trace detection of 8-OH-dG. But it can be eliminated completely by uricase. The as-prepared ss DNA/GNs/GCE will be promising for the detection of 8-OH-dG in real samples. PMID- 25128368 TI - Associations between different types of hypoglycemic agents and the clinical outcome of percutaneous coronary intervention in diabetic patients-From the FU Registry. AB - BACKGROUND: It is not clear whether it is reasonable to use particular drugs for glycemic control in preference to other hypoglycemic agents in terms of the clinical outcome of percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM). METHODS AND RESULTS: Among 2148 patients (2568 lesions) in the FU-Registry, DM patients who underwent PCI (n=758; 922 lesions) were investigated to clarify the effects of various drugs for glycemic control on the clinical outcome [major adverse cardiac events (MACEs): death, myocardial infarction (MI), and target lesion revascularization (TLR)] over approximately 300 days of follow-up (UMIN000005679). The MACEs(+) group (n=165) had a higher usage of insulin (p<0.001) and a lower usage of biguanides (BG, p<0.05) and dipeptidyl peptidase-IV inhibitors (p<0.05) at PCI, compared to the MACEs(-) group (n=593). A multivariate logistic regression analysis showed that low density lipoprotein cholesterol, insulin use, atherosclerosis obliterans, and lesion reference might be significantly associated with MACEs, while BG use was negatively correlated with MACEs (p=0.04). The cumulative frequency of MACEs in the insulin-treated group was significantly higher (p<0.05) than that in the non insulin group, and the strongest association between insulin with MACEs was seen in the hemoglobin (Hb) A1c 6.5-7.5% group. There tended to be a negative correlation between the use of insulin and MACEs, with risk ratios of <1, for the HbA1c >8.5% groups. CONCLUSIONS: Among different hypoglycemic agents, treatment with insulin was associated with poor mid-term clinical outcomes in DM patients who underwent PCI, while BG use was negatively correlated with MACEs. It may be reasonable for patients with HbA1c >8.5% to avoid hyperglycemia and glucotoxicity, even through the use of insulin. PMID- 25128369 TI - Expression of Caenorhabditis elegans-expressed Trans-HPS, partial aminopeptidase H11 from Haemonchus contortus. AB - Aminopeptidase H11 present in the surface of intestine microvilli in Haemonchus contortus was identified as the most effective antigen candidate. However, its recombinant forms produced in Escherichiacoli, insect cells and yeast could not provide promising protection against H. contortus challenge, probably due to the inappropriate glycosylation and/or conformational folding. Herein, partial H11 containing the potential zinc-binding domain and two predicted glycosylation sites (nt 1 bp-1710 bp, Trans-HPS) was subcloned downstream of 5' flanking region of Caenorhabditis elegans cpr-1 gene in pPD95.77 vector, with the deletion of GFP gene. The recombinant was expressed in C. elegans and verified by blotting with anti-H11 and anti-Trans-HPS rabbit polyclonal antibodies and anti-His monoclonal antibody. Stably inherited Trans-HPS in worm descendants was achieved by integration using UV irradiation. Immunization with the crude Trans-HPS extracted from transgenic worms resulted in 37.71% reduction in faecal egg counts (FEC) (P<0.05) and 24.91% reduction in worm burden, but an upward curve with moderate rate of daily FEC in goats. These results suggested an apparent delay against H. contortus egg-laying in goats, which differed from that with bacteria-origin form of partial H11 (nt 670 bp-1710 bp, HPS) (26.04% reduction in FEC and 18.46% reduction in worm burden). These findings indicate the feasibility of sufficient C. elegans-expressed H11 for the immunological research and vaccine development. PMID- 25128370 TI - Facts, myths and hypotheses on the zoonotic nature of Mycobacterium avium subspecies paratuberculosis. AB - Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of paratuberculosis (Johne's disease [JD]), a chronic granulomatous enteritis in ruminants. JD is one of the most widespread bacterial diseases of domestic animals with significant economic impact. The histopathological picture of JD resembles that of Crohn's disease (CD), a human chronic inflammatory bowel disease of still unresolved aetiology. An aetiological relevance of MAP for CD has been proposed. This and the ambiguity of other published epidemiological findings raise the question whether MAP represents a zoonotic agent. In this review, we will discuss evidence that MAP has zoonotic capacity. PMID- 25128371 TI - Implementation and monitoring of oral rabies vaccination of foxes in Kosovo between 2010 and 2013--an international and intersectorial effort. AB - The European Union has used instrument for pre-accession (IPA) funds to provide technical assistance and supplies for the eradication, monitoring and control of rabies in several pre-accession countries. As a result, since 2010, multi-annual oral rabies vaccination (ORV) programmes for eliminating fox rabies have been launched in six Western Balkan countries. Here the implementation of the ORV programme in Kosovo, the smallest of the West Balkan countries, is described. Associated challenges under difficult political conditions, potential biases, and the results of rabies surveillance and monitoring of ORV campaigns (bait uptake and immunisation rates) since 2010 are reported. PMID- 25128372 TI - Joint issues--conflicts of interest, the ASR hip and suggestions for managing surgical conflicts of interest. AB - BACKGROUND: Financial and nonfinancial conflicts of interest in medicine and surgery are troubling because they have the capacity to skew decision making in ways that might be detrimental to patient care and well-being. The recent case of the Articular Surface Replacement (ASR) hip provides a vivid illustration of the harmful effects of conflicts of interest in surgery. DISCUSSION: We identify financial and nonfinancial conflicts of interest experienced by surgeons, hospitals and regulators in the ASR case. These conflicts may have impacted surgical advice, decision-making and evidence gathering with respect to the ASR prosthesis, and contributed to the significant harms experienced by patients in whom the hip was implanted. Drawing on this case we explore shortcomings in the standard responses to conflicts of interest--disclosure and recusal. We argue disclosure is necessary but by no means sufficient to address conflicts of interest. Using the concept of recusal we develop remedies including second opinions and third party consent which may be effective in mitigating conflicts, but their implementation introduces new challenges. SUMMARY: Deployment of the ASR hip is a case of surgical innovation gone wrong. As we show, there were multiple conflicts of interest involved in the introduction of the ASR hip into practice and subsequent attempts to gloss over the mounting body of evidence about its lack of safety and effectiveness. Conflicts of interest in surgery are often not well managed. We suggest strategies in this paper which can minimise the conflicts of interest associated with surgical innovation. PMID- 25128373 TI - Application and assessment of optical clearing methods for imaging of tissue engineered neural stem cell spheres. AB - Three-dimensional (3D) cell culture is an important tool that facilitates biological discoveries by bridging the divide between standard two-dimensional cell culture and the complex, high-cell-density in vivo environment. Typically, the internal structures of 3D tissue-engineered samples are visualized through an involved process of physical sectioning, immunostaining, imaging, and computational reconstruction. However, recent progress in tissue-clearing methods has improved optical-imaging-depth capabilities in whole embryos and brains by reducing tissue opacity and light scattering, thus decreasing the need for physical sectioning. In this study, we assessed the application of the recently published clearing techniques Clear(T2), Scale, and SeeDB to tissue-engineered neural spheres. We found that scaffold-free self-assembled adult hippocampal neural stem cell spheres of 100-MUm diameter could be optically cleared and imaged using either Clear(T2) or Scale, while SeeDB only marginally improved imaging depth. The Clear(T2) protocol maintained sphere size, while Scale led to sample expansion, and SeeDB led to sample shrinkage. Additionally, using Clear(T2) we cleared and successfully imaged spheres of C6 glioma cells and spheres of primary cortical neurons. We conclude that Clear(T2) is the most effective protocol of those tested at clearing neural spheres of various cell types and could be applied to better understand neural cell interactions in 3D tissue-engineered samples. PMID- 25128374 TI - siRNA therapy in cutaneous T-cell lymphoma cells using polymeric carriers. AB - Cutaneous T-cell lymphomas (CTCLs) arise from specific molecular aberrations that lead to uncontrolled cell proliferation. RNA interference (RNAi) with short interfering RNAs (siRNAs) is a feasible approach to interrupt aberrant signal processing in CTCL cells, but functional biomaterial carriers are needed to effectively deliver siRNAs intracellularly. Towards this goal, we explored the utility of lipid-substituted polyethylenimines (PEI) carriers in a cell model of CTCL. Using caprylic and linoleic acid substituted 2 kDa PEI (PEI-CA and PEI-LA, respectively), we showed effective delivery of siRNA to T-lymphocyte Hut78 and Jurkat cells, but silencing of a model protein (Green Fluorescent Protein, GFP) was possible only in the Hut78 cells. To enhance siRNA delivery to Hut78 cells, a high siRNA: carrier ratio used to assemble the complexes and centrifugation of cells in the presence of complexes were found effective. The toxicities of PEI-CA and PEI-LA were significantly lower than other commercial carriers, 25 kDa PEI and Lipofectamine((r)) RNAiMAX. This might have contributed to reduced siRNA delivery efficiency of the latter carriers. Screening several endogenous targets led us to identify phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and cyclin-dependent kinase 18 (CDK18) as viable targets to induce siRNA-mediated cell growth inhibition. The results of this study identified promising polymeric carriers and molecular targets that could control proliferation of CTCL cells based on RNAi therapy. PMID- 25128375 TI - Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes. AB - Implantable neural electrodes must drastically improve chronic recording stability before they can be translated into long-term human clinical prosthetics. Previous studies suggest that sub-cellular sized and mechanically compliant probes may result in improved tissue integration and recording longevity. However, currently these design features are restricted by the opposing mechanical requirements needed for minimally damaging insertions. We designed a non-cytotoxic, carboxymethylcellulose (CMC) based dissolvable delivery vehicle (shuttle) to provide the mechanical support for insertion of ultra-small, ultra-compliant microfabricated neural probes. Stiff CMC-based shuttles rapidly soften immediately after being placed ~1 mm above an open craniotomy as they absorb vapors from the brain. To address this, we developed a sophisticated targeting, high speed insertion (~80 mm/s), and release system to implant these shuttles. After implantation, the goal is for the shuttle to dissolve away leaving only the electrodes behind. Here we show the histology of chronically implanted shuttles of large (300 MUm * 125 MUm) and small (100 MUm * 125 MUm) size at discrete time points over 12 weeks. Early time points show the CMC shuttle expanded after insertion as it absorbed moisture from the brain and slowly dissolved. At later time points neuronal cell bodies populate regions within the original shuttle tract. The large CMC shuttles show that the CMC expansion can cause extended secondary damage. On the other hand, the smaller CMC shuttles show limited secondary damage, wound closure by 4 weeks, absence of activated microglia at 12 weeks, as well as evidence suggesting neural regeneration at the implant site. This shuttle, therefore, shows great promise facilitating the implantation of nontraditional ultra-small, and ultra-compliant probes. PMID- 25128376 TI - The influence of age on adaptive bone formation and bone resorption. AB - Bone is a tissue with enormous adaptive capacity, balancing resorption and formation processes. It is known that mechanical loading shifts this balance towards an increased formation, leading to enhanced bone mass and mechanical performance. What is not known is how this adaptive response to mechanical loading changes with age. Using dynamic micro-tomography, we show that structural adaptive changes of trabecular bone within the tibia of living mice subjected to two weeks of in vivo cyclic loading are altered by aging. Comparisons of 10, 26 and 78 weeks old animals reveal that the adaptive capacity diminishes. Strikingly, adaptation was asymmetric in that loading increases formation more than it reduces resorption. This asymmetry further shifts the (re)modeling balance towards a net bone loss with age. Loading results in a major increase in the surface area of mineralizing bone. Interestingly, the resorption thickness is independent of loading in trabecular bone in all age groups. This data suggests that during youth, mechanical stimulation induces the recruitment of bone modeling cells whereas in old age, only bone forming cells are affected. These findings provide mechanistic insights into the processes that guide skeletal aging in mice as well as in other mammals. PMID- 25128379 TI - Lippes Loop intrauterine device left in the uterus for 50 years: case report. AB - BACKGROUND: The first Lippes Loop intrauterine device (IUD) was introduced in 1962. It was a plastic double "S" loop, a trapezoid shaped IUD that closely fit around the contours of the uterine cavity, reducing the incidence of expulsion. This IUD was commonly used from the 1960's to the 1980's. Some authors state that the IUD can be left in the uterine cavity for an indefinite amount of time. Prolonged use of this device was common, however, it was associated with some complications like uterine bleeding during post-menopausal period and inflammatory pelvic diseases. CASE PRESENTATION: The patient was a 74-years-old woman who was admitted to a university hospital due to urinary incontinence stress. The patient's history included 2 deliveries and 20 years of menopause. During ultrasonography a normally sized and shaped uterus was found. The uterine cavity was expanded by 14 mm with some fluid. A "Lippes" loop was also seen in the uterine cavity. Both ovaries were atrophic without any abnormalities. The patient had her IUD inserted 50 years ago. Patient underwent TOT (tension obturator tape ) surgery for urinary incontinence. Evacuation of IUD and uterine curettage was also done. CONCLUSIONS: Fifty years of prolonged usage of LIPPES IUD had no influence on the woman's health during our case. PMID- 25128377 TI - Ischemic preconditioning affects long-term cell fate through DNA damage-related molecular signaling and altered proliferation. AB - Despite the potential of ischemic preconditioning for organ protection, long-term effects in terms of molecular processes and cell fates are ill defined. We determined consequences of hepatic ischemic preconditioning in rats, including cell transplantation assays. Ischemic preconditioning induced persistent alterations; for example, after 5 days liver histology was normal, but gamma glutamyl transpeptidase expression was observed, with altered antioxidant enzyme content, lipid peroxidation, and oxidative DNA adducts. Nonetheless, ischemic preconditioning partially protected from toxic liver injury. Similarly, primary hepatocytes from donor livers preconditioned with ischemia exhibited undesirably altered antioxidant enzyme content and lipid peroxidation, but better withstood insults. However, donor hepatocytes from livers preconditioned with ischemia did not engraft better than hepatocytes from control livers. Moreover, proliferation of hepatocytes from donor livers preconditioned with ischemia decreased under liver repopulation conditions. Hepatocytes from donor livers preconditioned with ischemia showed oxidative DNA damage with expression of genes involved in MAPK signaling that impose G1/S and G2/M checkpoint restrictions, including p38 MAPK regulated or ERK-1/2-regulated cell-cycle genes such as FOS, MAPK8, MYC, various cyclins, CDKN2A, CDKN2B, TP53, and RB1. Thus, although ischemic preconditioning allowed hepatocytes to better withstand secondary insults, accompanying DNA damage and molecular events simultaneously impaired their proliferation capacity over the long term. Mitigation of ischemic preconditioning-induced DNA damage and deleterious molecular perturbations holds promise for advancing clinical applications. PMID- 25128378 TI - Psycho-social impact of visual impairment on health-related quality of life among nursing home residents. AB - BACKGROUND: Visual impairment (VI) affects physical, psychological, and emotional well-being, and social life as well. The purpose of this exploratory study was to assess the psycho-social impact of VI on health-related quality of life (HRQoL) among nursing home residents. METHODS: This cross-sectional study involved 272 residents of 60 years or older residing in seven nursing homes of the Kathmandu Valley, Nepal. Comprehensive ocular examinations, including near and distance vision assessment and refractions were carried out. VI was defined as visual acuity (VA) less than 6/18 in the better eye. Residents were divided into two groups: one group did not have VI (in whom VA was greater than or equal to 6/18 in the better eye), and the other had VI (in whom VA was worse than 6/18 in the better eye).Face-to-face interviews were conducted filling out a 36-item The Medical Outcomes Study Short-Form (SF-36) questionnaire. The SF-36 questionnaire was scored according to the scoring algorithm SF-36 subscales. RESULTS: The mean age of residents was 74.68 +/- 8.19 years (range, 60-99 years) and the majority were female (78.68%). The mean composite score of SF-36 was 46.98 +/- 13.08. VI detrimentally affected scores of both the physical and the mental components, but the impact of VI was slightly greater for the physical component than that for the mental component. There was a trend towards a lower composite score as well as each subscale score of the SF-36 in participants with VI than in those without VI. CONCLUSION: VI has a negative effect on HRQoL. HRQoL is reduced among nursing home residents and the reduction in the HRQoL bears a positive association with VI. PMID- 25128380 TI - [Some points on the diagnosis of microscopic colitis]. PMID- 25128381 TI - Doxycycline exerts multiple anti-allergy effects to attenuate murine allergic conjunctivitis and systemic anaphylaxis. AB - Allergic diseases, which affect up to 20-30% of the world population, are still therapeutic challenge for allergists. Tetracyclines, which belong to an antibiotic drug family that possesses a striking variety of non-antibiotic properties, have been successfully applied to a wide range of diseases. However, their roles in allergic conjunctivitis and anaphylaxis and their underlying anti allergy mechanisms remain elusive. Here, we reported that treatment with doxycycline significantly reduced IgE release from mouse B cells and the degranulation and inflammatory cytokines production of mouse mast cells (MCs) activated by IgE-dependent way. Furthermore, doxycycline treatment significantly inhibited histamine-induced vascular hyperpermeability in vitro. Mechanistically, the doxycycline-mediated inhibition of B cells, MCs and histamine may occur via modulation of the PI3K/Akt pathway. In vivo, our results demonstrated that treatment with doxycycline significantly attenuated clinical symptoms of mouse models of experimental allergic conjunctivitis (EAC) with a significant decrease in inflammatory cell frequency, IgE production, histamine release, and a decrease in TNF-alpha and IL-4 production. Using mouse models of MCs-dependent passive systemic anaphylaxis (PSA), we further confirmed anti-allergy effects of doxycycline and doxycycline-mediated inhibitory effects on MCs. Furthermore, our results showed that doxycycline significantly attenuate histamine-induced systemic anaphylaxis-like reaction (HISA) with a significantly downregulation of PI3K/Akt/eNOS/VE-cadherin pathway. The doxycycline-mediated anti-allergy effects during EAC, PSA and HISA were abrogated when an Akt activator, SC79, was administered. These findings suggest that doxycycline inhibits B cell, MC and histamine function and attenuates experimental allergic conjunctivitis and systemic anaphylaxis by possible modulating the PI3K/Akt pathway. PMID- 25128382 TI - Paris saponin VII suppressed the growth of human cervical cancer Hela cells. AB - BACKGROUND: Saponins of several herbs are known to induce apoptosis in many cancer cells. The present study aimed to investigate the growth inhibitory effect of Paris saponin VII (PS VII), a kind of steroidal saponins from Chonglou (Rhizoma Paridis Chonglou), on the human cervical cancer cell line Hela and the relative molecular mechanisms. METHODS: Hela cells were exposed to different concentrations of PS VII (1 to 100 MUM). Inhibition of cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) assays. The amount of apoptotic cells was evaluated by flow cytometric analysis. And the protein level of cleaved caspase 3, cleaved caspase-9, Bax, and Bcl-2 was evaluated by Western blot. RESULTS: The half maximal inhibitory concentration (IC50) value of PS VII for the growth inhibition of Hela cells was 2.62 +/- 0.11 MUM. PS VII increased the expression of caspase-3, caspase-9, and Bax while decreased that of Bcl-2, suggesting that PS VII may induce apoptosis through intrinsic apoptotic ways. CONCLUSIONS: These data indicate that PS VII has the potential for the treatment of cervical cancer. PMID- 25128383 TI - Radiodense ligament markers for radiographic evaluation of anterior cruciate ligament reconstruction. AB - INTRODUCTION: Early clinical and radiographic diagnosis of failed or loosened anterior cruciate ligament (ACL) reconstructions can be challenging. The aim of the present study is to retrospectively evaluate the use of radiologically visible markers in the ACL graft, serving as a potential diagnostic tool in ACL graft rupture and insufficiency. METHODS: Twenty patients were included in the study. ACL reconstruction was performed with use of a hamstring autograft in hybrid fixation technique. The graft was marked with two radiodense suture knots, one at the tibial and femoral tunnel openings. Radiographs were performed postoperatively, after 6 weeks and 12 months. Four distances between markers and landmarks were measured in anteroposterior and three in lateral radiographic views and the positional change between the timepoints of measurement was calculated. RESULTS: Measurements of the marker distances on radiographs showed an excellent interobserver reliability (kappa=0.97). In two measured distal anteroposterior distances statistically significant changes could be detected between 6 weeks and 12 months postoperatively in one patient with MRI-documented ACL rerupture and in five patients with ACL elongation defined as anteroposterior translation with side-to-side difference of >=3 mm measured with a Rolimeter device. On lateral radiographs, marker distances were highly variable and did not correlate with clinical ACL elongation. CONCLUSION: The application of radiodense ACL graft markers is a straight-forward, non-expensive and potentially useful diagnostic tool to identify the position of the transplant and for diagnosis of graft elongation or failure. However, the method is sensitive to the radiological projection, which should be further studied and optimized. PMID- 25128384 TI - Coronal tibiofemoral subluxation: a new measurement method. AB - BACKGROUND: Coronal tibiofemoral (CTF) subluxation is a common finding in knee osteoarthritis (OA) which can be related to poor pain scores and tibial spine impingement. In this study we describe a new method for measuring CTF subluxation and present validation of the method using cadaveric knees. METHODS: A prototype software code based on the ICP mathematical algorithm was developed to measure CTF subluxation; the code finds the rigid transformation that best aligns the articular surfaces, measures CTF subluxation and the angle between articular surfaces. For validation, three stripped fresh frozen cadaveric knee specimens were transfixed to a specially designed knee fixation device where tibiofemoral angle and CTF subluxation can be measured directly. Fluoroscopic images were obtained with the tibiofemoral joint in neutral alignment and with 5, 10 and 15 (mm) of medial and lateral subluxation. This procedure was repeated with a neutral tibiofemoral angle, 10 degrees of varus and 10 degrees of valgus. All images were analyzed independently by two investigators using the prototype software. RESULTS: The interclass correlation coefficient between the two investigators for CTF subluxation and tibiofemoral angle was 0.93 and 0.99 respectively. The CTF subluxation and tibiofemoral angle measured by the software correlated to the CTF subluxation and tibiofemoral angle were defined using the knee fixation device, with Pearson product moments of 0.86 and 0.94 respectively. CONCLUSION: Our suggested prototype software is precise, repeatable and reliable at measuring CTF subluxation and tibiofemoral angle. It may prove to be a useful tool to evaluate CTF subluxation in a clinical setting. PMID- 25128385 TI - National health policy-makers' views on the clarity and utility of Countdown to 2015 country profiles and reports: findings from two exploratory qualitative studies. AB - BACKGROUND: The use of sets of indicators to assess progress has become commonplace in the global health arena. Exploratory research has suggested that indicators used for global monitoring purposes can play a role in national policy making, however, the mechanisms through which this occurs are poorly understood. This article reports findings from two qualitative studies that aimed to explore national policy-makers' interpretation and use of indicators from country profiles and reports developed by Countdown to 2015. METHODS: An initial study aimed at exploring comprehension of Countdown data was conducted at the 2010 joint Women Deliver/Countdown conference. A second study was conducted at the 64th World Health Assembly in 2011, specifically targeting national policy makers. Semi-structured interviews were carried out with 29 and 22 participants, respectively, at each event. Participants were asked about their understanding of specific graphs and indicators used or proposed for use in Countdown country profiles, and their perception of how such data can inform national policy making. Responses were categorised using a framework analysis. RESULTS: Respondents in both studies acknowledged the importance of the profiles for tracking progress on key health indicators in and across countries, noting that they could be used to highlight changes in coverage, possible directions for future policy, for lobbying finance ministers to increase resources for health, and to stimulate competition between neighbouring or socioeconomically similar countries. However, some respondents raised questions about discrepancies between global estimates and data produced by national governments, and some struggled to understand the profile graphs shown in the absence of explanatory text. Some respondents reported that use of Countdown data in national policy-making was constrained by limited awareness of the initiative, insufficient detail in the country profiles to inform policy, and the absence of indicators felt to be more appropriate to their own country contexts. CONCLUSIONS: The two studies emphasise the need for country consultations to ensure that national policy-makers understand how to interpret and use tools like the Countdown profile for planning purposes. They make clear the value of qualitative research for refining tools used to promote accountability, and the need for country level Countdown-like processes. PMID- 25128386 TI - The histone deacetylase inhibitor trichostatin A induces neurite outgrowth in PC12 cells via the epigenetically regulated expression of the nur77 gene. AB - Histone deacetylase (HDAC) inhibitors induce histone acetylation and gene expression by changing local chromatin structures. They can thereby influence various cells to proliferate or differentiate. It has been reported that trichostatin A (TSA) or valproic acid (VPA) can induce the neuronal differentiation of mouse embryonic neural stem cells and rat cerebellar granule cells. It is unclear however which gene is responsible for the neuronal differentiation induced by HDAC inhibitors. In this study, we investigated the contribution of immediate early gene (IEG) nur77 to the neuronal differentiation induced by TSA. We report that TSA induces neurite outgrowth in PC12 cells, and C646, an inhibitor of HAT (histone acetyl transferase) (p300), prevents TSA induced neurite formation. The acetylation of the Lys14 residue of histone H3, and mRNA and protein expression of nur77 gene were found to be stimulated after treatment with TSA, but not in the presence of C646. A knock-down of nur77 inhibits the neurite outgrowth induced by TSA. Furthermore, the ectopic expression of nur77 significantly elicits neurite formation in PC12 cells. These results suggest that the expression of nur77, which is up-regulated via the TSA induced acetylation of Lys14 on histone H3, is essential for the neuronal differentiation in TSA-induced PC12 cells. PMID- 25128389 TI - Mesenchymal change and drug resistance in neuroblastoma. AB - BACKGROUND: Metastatic initiation has many phenotypic similarities to epithelial to-mesenchymal transition, including loss of cell-cell adhesion, increased invasiveness, and increased cell mobility. We have previously demonstrated that drug resistance is associated with a metastatic phenotype in neuroblastoma (NB). The purpose of this project was to determine if the development of doxorubicin resistance is associated with characteristics of mesenchymal change in human NB cells. MATERIALS AND METHODS: Total RNA was isolated from wild type (WT) and doxorubicin-resistant (DoxR) human NB cell lines (SK-N-SH and SK-N-BE(2)C) and analyzed using the Illumina Human HT-12 version 4 Expression BeadChip. Differentially expressed genes (DEGs) were identified. Volcano plots and heat maps were generated. Genes of interest with a fold change in expression >1.5 and an adjusted P < 0.1 were analyzed. Immunofluorescence (IF) and Western blot analysis confirmed microarray results of interest. Matrigel invasion assay and migration wounding assays were performed. RESULTS: Volcano plots and heat maps visually demonstrated a similar pattern of DEGs in the SK-N-SH and SK-N-BE(2)C DoxR cell lines relative to their parental WT lines. Venn diagramming revealed 1594 DEGs common to both DoxR cell lines relative to their parental cell lines. Network analysis pointed to several significantly upregulated epithelial-to mesenchymal transition pathways, through TGF-beta pathways via RhoA, PI3K, and ILK and via SMADs, as well as via notch signaling pathways. DoxR cell lines displayed a more invasive phenotype than respective WT cell lines. CONCLUSIONS: Human SK-N-SH and SK-N-BE(2)C NB cells display characteristics of mesenchymal change via multiple pathways in the transition to a drug-resistant state. PMID- 25128387 TI - Vagal nerve stimulation blocks interleukin 6-dependent synaptic hyperexcitability induced by lipopolysaccharide-induced acute stress in the rodent prefrontal cortex. AB - The ratio between synaptic inhibition and excitation (sI/E) is a critical factor in the pathophysiology of neuropsychiatric disease. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in sI/E in the rodent temporal cortex. The aim of the present study was to determine whether a similar mechanism takes place in the prefrontal cortex, and to elaborate strategies to prevent or attenuate it. We used aseptic inflammation (single acute injections of lipopolysaccharide, LPS, 10mg/kg) as stress model, and patch-clamp recording on a prefrontal cortical slice preparation from wild-type rat and mice, as well as from transgenic mice in which the inhibitor of IL-6 trans-signaling sgp130Fc was produced in a brain-specific fashion (sgp130Fc mice). The anti inflammatory reflex was activated either by vagal nerve stimulation or peripheral administration of the nicotinic alpha7 receptor agonist PHA543613. We found that the IL-6-dependent reduction in prefrontal cortex synaptic inhibition was blocked in sgp130Fc mice, or - in wild-type animals - upon application sgp130Fc. Similar results were obtained by activating the "anti-inflammatory reflex" - a neural circuit regulating peripheral immune response - by stimulation of the vagal nerve or through peripheral administration of the alpha7 nicotinic receptor agonist PHA543613. Our results indicate that the prefrontal cortex is an important potential target of IL-6 mediated trans-signaling, and suggest a potential new avenue in the treatment of a large class of hyperexcitable neuropsychiatric conditions, including epilepsy, schizophrenic psychoses, anxiety disorders, autism spectrum disorders, and depression. PMID- 25128390 TI - The first report of Telomerina flavipes (Meigen, 1830) (Diptera, Sphaeroceridae) in a forensic case, with redescription of its pupa. AB - This paper presents a forensic investigation that took place in the city of Murcia (SE Spain) and shows how the entomological specimens collected at the scene were extremely helpful for estimating the minimum post-mortem interval (PMImin). The occurrence of Telomerina flavipes (Meigen, 1830) (Diptera: Sphaeroceridae) is reported here for the first time in a forensic case. Additionally, the importance of other entomological evidence in this case is discussed. The first known images of the puparium are provided, as well as its redescription and that of the cephalopharyngeal skeleton recovered from the puparium. PMID- 25128388 TI - Structural insights into +1 frameshifting promoted by expanded or modification deficient anticodon stem loops. AB - Maintenance of the correct reading frame on the ribosome is essential for accurate protein synthesis. Here, we report structures of the 70S ribosome bound to frameshift suppressor tRNA(SufA6) and N1-methylguanosine at position 37 (m(1)G37) modification-deficient anticodon stem loop(Pro), both of which cause the ribosome to decode 4 rather than 3 nucleotides, resulting in a +1 reading frame. Our results reveal that decoding at +1 suppressible codons causes suppressor tRNA(SufA6) to undergo a rearrangement of its 5' stem that destabilizes U32, thereby disrupting the conserved U32-A38 base pair. Unexpectedly, the removal of the m(1)G37 modification of tRNA(Pro) also disrupts U32-A38 pairing in a structurally analogous manner. The lack of U32-A38 pairing provides a structural correlation between the transition from canonical translation and a +1 reading of the mRNA. Our structures clarify the molecular mechanism behind suppressor tRNA-induced +1 frameshifting and advance our understanding of the role played by the ribosome in maintaining the correct translational reading frame. PMID- 25128391 TI - Antiviral efficacy analysis of telbivudine concurrent with the first cycle of chemotherapy in HBsAg-positive lymphoma patients. AB - BACKGROUND: HBV reactivation is a common complication in HBsAg-positive lymphoma patients with chemotherapy or immunotherapy. There is no standard antiviral treatment for these patients undergoing chemotherapy or immunotherapy. The initial time, the agent and the duration time are confused at present. OBJECTIVE: This study aimed to investigate the antiviral efficacy of telbivudine concurrent with initiation of chemotherapy in HBsAg-positive patients with lymphoma. STUDY DESIGN: Between April 2008 and October 2012, 359 patients with pathological diagnoses of lymphoma were admitted to the hospital. Among those, a cohort of 60 HBsAg-positive cases were included in this retrospective study, and telbivudine was taken at the same day or one day prior to the first cycle of chemotherapy. The rates of HBV reactivation, virological response, undetectable HBV DNA, the relationship between HBV reactivation and its clinical characteristics were investigated. RESULTS: The rate of HBV reactivation was 11.7% (7/60), while it was 17.5% (7/40) and 75% (3/4) in patients treated with rituximab based chemotherapy and rituximab maintenance therapy, respectively. The fulminant hepatitis rate was 6.6%. The rates of virological response, undetectable HBV DNA and ALT normalization were 88.3%, 61.7% and 83.3%, respectively. HBV reactivation was associated with rituximab (P = 0.013), and HBeAg-negativity (P = 0.016), but not correlated with age, gender, clinical stages, extranodal disease, bone marrow involvement, B symptoms, HBV viral loads or serum LDH level. CONCLUSION: Concurrent telbivudine treatment with initial chemotherapy can effectively reduce HBV reactivation in HBsAg-positive lymphoma patients, and the efficacy is independent of the baseline HBV viral loads. PMID- 25128392 TI - Vibration transmission to lower extremity soft tissues during whole-body vibration. AB - In order to evaluate potential risks of whole-body vibration (WBV) training, it is important to understand the transfer of vibrations from the WBV platform to the muscles. Therefore, the purpose of this study was to quantify the transmissibility of vibrations from the WBV platform to the triceps surae and quadriceps soft tissue compartments. Sixteen healthy, male participants were exposed to side-altering WBV at 2.5mm amplitude and frequencies of 10, 17 and 28 Hz. Acceleration signals were measured at the platform and at the soft tissue compartments using tri-axial accelerometers. Transmissibility of peak acceleration and peak amplitude for both tested soft tissue compartments was high at 10 Hz (2.1-2.3), moderate at 17 Hz (1.1-1.9) and low at 28 Hz (0.5-1.2). The average peak acceleration was 125.4 ms(-2) and 46.5 ms(-2) for the triceps surae and quadriceps at 28 Hz, respectively. The muscles' vibration frequency was equal to the input frequency of the WBV platform (p<0.05). The transfer of vibrations to the muscles is strongly dependent on the platform frequency and the particular muscle of interest. The acceleration measured at the triceps surae was higher than the corresponding accelerations related to soft tissue injury in animal studies but neither existing regulations nor the comparison to available animal studies seem appropriate to make inferences on injury risk. More realistic animal or computational muscle models may use the current data to evaluate potentially unwanted side effects of WBV training. PMID- 25128394 TI - [Professional politics - for our patients?]. PMID- 25128393 TI - Pulmonary artery relative area change is inversely related to ex vivo measured arterial elastic modulus in the canine model of acute pulmonary embolization. AB - A low relative area change (RAC) of the proximal pulmonary artery (PA) over the cardiac cycle is a good predictor of mortality from right ventricular failure in patients with pulmonary hypertension (PH). The relationship between RAC and local mechanical properties of arteries, which are known to stiffen in acute and chronic PH, is not clear, however. In this study, we estimated elastic moduli of three PAs (MPA, LPA and RPA: main, left and right PAs) at the physiological state using mechanical testing data and correlated these estimated elastic moduli to RAC measured in vivo with both phase-contrast magnetic resonance imaging (PC-MRI) and M-mode echocardiography (on RPA only). We did so using data from a canine model of acute PH due to embolization to assess the sensitivity of RAC to changes in elastic modulus in the absence of chronic PH-induced arterial remodeling. We found that elastic modulus increased with embolization-induced PH, presumably a consequence of increased collagen engagement, which corresponds well to decreased RAC. Furthermore, RAC was inversely related to elastic modulus. Finally, we found MRI and echocardiography yielded comparable estimates of RAC. We conclude that RAC of proximal PAs can be obtained from either MRI or echocardiography and a change in RAC indicates a change in elastic modulus of proximal PAs detectable even in the absence of chronic PH-induced arterial remodeling. The correlation between RAC and elastic modulus of proximal PAs may be useful for prognoses and to monitor the effects of therapeutic interventions in patients with PH. PMID- 25128399 TI - [Differential diagnosis of hematuria]. AB - Hematuria is the main symptom of many urological and nephrological diseases. In the differential diagnostics a distinction is made between painful and pain-free and between macrohematuria which is visible to the naked eye and microhematuria which is not visible. The reasons for hematuria are basically renal (glomerular) and non-renal (non-glomerular) causes. In order not to overlook early symptoms of malignant and relevant benign diseases and also to avoid excessive diagnostic tests, a differentiated approach is necessary. PMID- 25128395 TI - [Certification system in urological healthcare : a professional political evaluation]. AB - There have been function and organ-related certification systems in urology for a long time. The aim of such certificates is the optimization of patient care above the defined minimum standards and intensification of interdisciplinary cooperation. Whether such certificates have led to better patient care has not been proven. The obligatory documentation in epidemiological cancer registries, which has been taken up by legislature, will in future lead to so-called clinical cancer registries in which the complete course of treatment must be entered. With these registries the quality of healthcare can be compared between individual institutions. Until now, quality of care data outside oncology are lacking. Urology would also benefit from a registry with quality of care data for these patients. PMID- 25128400 TI - National trends and disparities in cervical cancer screening among commercially insured Women, 2001-2010. AB - BACKGROUND: Previous surveys reported declining cervical cancer screening rates from 2000 to 2010, but trends by key demographic and age groups are less clear. METHODS: We examined 3-year Papanicolaou (Pap) test rates among 4.2 million women enrolled in a large national health plan during 2001 to 2010. We calculated and plotted adjusted 3-year rates stratified by age and key neighborhood-level socioeconomic characteristics including poverty level and race/ethnicity (white, black, Hispanic, and mixed ethnicity neighborhood). We fitted trends in 2001-2010 screening rates and socioeconomic disparities as annual percentage changes (APC) using joinpoint analysis. RESULTS: Women ages 21 to 29 years had estimated 3-year Pap testing rates of 81.3% to 81.4% over the decade. Estimated disparities by low high poverty level were 3.1% and 2.0% in 2001-2003 and 2008-2010, respectively, a nonsignificant decline. Initial white-black disparities were 4.0% and declined significantly from 2005-2007 to 2008-2010 to 2.8% at an APC of -0.65% (P = 0.021). White-Hispanic disparities declined from 4.3% to 0.8% over the decade, a 0.50% APC (P = 0.024). Among women ages 30 to 64 years, estimated 3-year Pap testing rates trended down from 76.1% to 71.8% over the decade [-0.94% APC (P < 0.001) until 2005-2007]. This pattern was similar among women from most categories of poverty and race/ethnicity. CONCLUSIONS: Among commercially insured women ages 21 to 29 years, 3-year Pap testing rates remained stable at 81% over the decade; disparities were small and improved for Hispanic women to a greater degree than for black women. Among women ages 30 to 64 years, 3-year Pap testing rates declined from 2001 to 2010. IMPACT: Cervical cancer screening should be promoted to achieve Healthy People 2020 goals. PMID- 25128401 TI - Smoking at diagnosis is an independent prognostic factor for cancer-specific survival in head and neck cancer: findings from a large, population-based study. AB - BACKGROUND: Some studies suggest smoking may result in poorer clinical outcomes in head and neck cancer, but the evidence is heterogeneous and some of it is poor quality. In a large, population-based, study we investigated: (i) whether smoking at diagnosis is an independent prognostic factor for cancer-specific survival in head and neck cancer; and (ii) whether the association varies by site and treatment. METHODS: Head and neck cancers (ICD10 C01-C14, and C30-32) diagnosed from 1994 to 2009 were abstracted from the National Cancer Registry Ireland, and classified by smoking status at diagnosis. Follow-up was for 5 years or until December 31, 2010. Multivariate Cox proportional hazards models were used to compare cancer-specific death rates in current, ex-, and never smokers. Subgroup analyses by site and treatment were conducted. RESULTS: In total, 5,652 head and neck cancers were included. At diagnosis, 24% were never smokers, 20% ex-smokers, and 56% current smokers. Compared with never smokers, current smokers had a significantly raised death rate from cancer [multivariate HR, 1.36; 95% confidence interval (CI), 1.21-1.53]. The association was similar after restriction to squamous cell tumors. A significantly increased cancer-related death rate was seen for current smokers with oral cavity, pharyngeal, and laryngeal cancers. The association was stronger in surgically treated patients [HR, 1.49; 95% CI, 1.25-1.79; P(interaction) = 0.01]. Neither radiotherapy nor chemotherapy modified the effect of smoking. CONCLUSIONS: Patients with head and neck cancer who smoke at diagnosis have a significantly increased cancer death rate. IMPACT: Greater efforts are needed to encourage and support smoking cessation in those at risk of, and diagnosed with, head and neck cancer. PMID- 25128402 TI - Improved stool DNA integrity method for early colorectal cancer diagnosis. AB - BACKGROUND: DNA integrity analysis could represent an alternative approach to the early detection of colorectal cancer. Previously, fluorescence long DNA (FL-DNA) in stools was extracted using a manual approach and analyzed by capillary electrophoresis assay (CE FL-DNA). We aimed to improve diagnostic accuracy using a simpler and more standardized method [Real Time PCR FL-DNA (RT FL-DNA)] for the detection of early malignant lesions in a population undergoing colorectal cancer screening. METHODS: From 241 stool samples, DNA was extracted using manual and semiautomatic extraction systems and analyzed using FL-DNA tests by CE and RT assays. The RT FL-DNA approach showed slightly higher sensitivity and specificity compared with the CE FL-DNA method. Furthermore, we compared the RT FL-DNA approach with the iFOBT report. RESULTS: Nonparametric ranking statistics were used to analyze the relationship between the median values of RT FL-DNA and the clinicohistopathologic characteristics. The median values of both variables were significantly higher in patients with cancer than in patients with noncancerous lesions. According to the Fagan nomogram results, the iFOBT and FL-DNA methods provided more accurate diagnostic information and were able to identify subgroups at varying risks of cancer. CONCLUSIONS: The combination of the semiautomatic extraction system and RT FL-DNA analysis improved the quality of DNA extracted from stool samples. IMPACT: RT FL-DNA shows great potential for colorectal cancer diagnosis as it is a reliable and relatively easy analysis to perform on routinely processed stool samples in combination with iFOBT. PMID- 25128403 TI - Prospective study of seroreactivity to JC virus T-antigen and risk of colorectal cancers and adenomas. AB - John Cunningham virus (JCV) is a common polyomavirus classified as a possible carcinogen by the International Agency for Research on Cancer. JCV may play a role in colorectal carcinogenesis, although we previously reported no association between JCV capsid antibodies and colorectal cancer. No studies have examined the role of seroreactivity to JCV T-antigen (T-Ag) oncoprotein in colorectal cancer. A case-control study nested within a community-based prospective cohort (CLUE II) was conducted. In 1989, 25,080 residents of Washington County, Maryland, were enrolled in CLUE II, completing baseline questionnaires and providing blood samples. At follow-up, 257 incident colorectal cancer cases were identified by linkage to population-based cancer registries through 2006 and matched to controls on age, sex, race, and date of blood draw. One hundred and twenty-three colorectal adenoma cases were identified through self-report during follow-up and matched to controls on age, sex, race, date of blood draw, and colorectal cancer screening. Baseline serum samples were tested for seroreactivity to JCV T-Ag. Associations between JCV T-Ag seroreactivity and colorectal cancer/adenomas were evaluated using conditional logistic regression models. Overall, seroreactivity to JCV T-Ag was not statistically significantly associated with the risk of either colorectal cancer [OR, 1.34; 95% confidence interval (CI), 0.89-2.01] or adenoma (OR, 1.30; 95% CI, 0.70-2.42), while a borderline association with colorectal cancer was observed among women (OR, 1.82; 95% CI, 1.00-3.31). Our past evaluation of JCV capsid seropositivity, combined with current findings, does not support a notable etiologic role for JCV infection in colorectal cancer. PMID- 25128404 TI - Increased intrathoracic and hepatic visceral adipose tissue independently correlates with coronary artery calcification in asymptomatic patients. AB - BACKGROUND: Visceral adipose tissue (VAT) is associated with cardiac events, but it is not clear which, if any of the various measures of VAT independently correlate with coronary artery disease (CAD). METHODS: We studied 400 patients undergoing computed tomography to determine coronary artery calcium (CAC) score. VAT was measured in the form of epicardial adipose tissue (EAT) volume and thickness, intrathoracic adipose tissue volume (ITAV), and hepatic steatosis. RESULTS: Of the 400 subjects, the average CAC score was 112.2 +/- 389.3. When each measure of VAT (EAT volume and thickness, ITAV, hepatic steatosis) was added to the traditional model (they were independently associated with greater risk of CAC score >=100 AU as measured by IDI/NRI (P < .05). On univariable logistic regression analysis, each of the 4 measures of VAT showed association with greater risk of a CAC score of >=100 AU (OR > 1). CONCLUSIONS: Each measure of VAT is a strong correlate of CAC score >=100 AU in asymptomatic subjects-these VAT assessments correlate more significantly than do traditional CAD risk factors. This incremental power in the predictive models is likely the result of measurement of a fundamental expression of the metabolic syndrome and consequent proatherogenic derangements. PMID- 25128405 TI - Characterisation of novel microRNAs in the Black flying fox (Pteropus alecto) by deep sequencing. AB - BACKGROUND: Bats are a major source of new and emerging viral diseases. Despite the fact that bats carry and shed highly pathogenic viruses including Ebola, Nipah and SARS, they rarely display clinical symptoms of infection. Host factors influencing viral replication are poorly understood in bats and are likely to include both pre- and post-transcriptional regulatory mechanisms. MicroRNAs are a major mechanism of post-transcriptional gene regulation, however very little is known about them in bats. RESULTS: This study describes 399 microRNAs identified by deep sequencing of small RNA isolated from tissues of the Black flying fox, Pteropus alecto, a confirmed natural reservoir of the human pathogens Hendra virus and Australian bat lyssavirus. Of the microRNAs identified, more than 100 are unique amongst vertebrates, including a subset containing mutations in critical seed regions. Clusters of rapidly-evolving microRNAs were identified, as well as microRNAs predicted to target genes involved in antiviral immunity, the DNA damage response, apoptosis and autophagy. Closer inspection of the predicted targets for several highly supported novel miRNA candidates suggests putative roles in host-virus interaction. CONCLUSIONS: MicroRNAs are likely to play major roles in regulating virus-host interaction in bats, via dampening of inflammatory responses (limiting the effects of immunopathology), and directly limiting the extent of viral replication, either through restricting the availability of essential factors or by controlling apoptosis. Characterisation of the bat microRNA repertoire is an essential step towards understanding transcriptional regulation during viral infection, and will assist in the identification of mechanisms that enable bats to act as natural virus reservoirs. This in turn will facilitate the development of antiviral strategies for use in humans and other species. PMID- 25128406 TI - The role of VEGF-A165b in trophoblast survival. AB - BACKGROUND: Pre-eclampsia remains a dominant cause of maternal and fetal mortality in developed countries. In a previous prospective study we identified a fall in the VEGF-A isoform VEGF-A165b in the plasma of patients in the first trimester to be a predictor of later pre-eclampsia. VEGF-A165b has been shown to have potent cytoprotective properties in many cell types. We therefore tested the hypothesis that VEGF-A165b may be cytoprotective for placental trophoblasts. METHODS: We used an immortalised first trimester trophoblast cell line exposed to chemical toxicity, and physiological (<2% O2) and atmospheric oxygen (21% O2) in the presence or absence of VEGF-A165b, angiogenic VEGF-A165a, a non-specific anti VEGF-A blocking antibody (bevacizumab), or a specific anti-VEGF-A165b antibody. Cell viability and cytotoxicity were measured by trypan blue and LDH assay respectively. RESULTS: Under high (21%) levels of oxygen, trophoblast viability was increased, and cytotoxicity reduced by exogenous recombinant VEGF-A165b (p < 0.05, n = 10) or VEGF-A165a. The cytoprotective effect was not seen under lower (<2%) oxygen conditions, where VEGF-A165b was upregulated. However inhibition of VEGF-A with blocking antibodies (bevacizumab or anti-VEGF-A165b) had marked cytotoxic effects under low oxygen conditions presumably through the blockade of autocrine survival pathways. CONCLUSIONS: These results show that when trophoblasts are exposed to lower oxygen tensions (as they are early in the 1st trimester) endogenous VEGF-A165b contributes to their survival through an autocrine pathway. In contrast in high oxygen conditions exogenous VEGF-A isoforms have a greater effect on trophoblast survival. PMID- 25128407 TI - Quantitation of substitutions at amino acid 70 in hepatitis C virus genotype 1b. AB - BACKGROUND: Substitutions of amino acid (aa) 70 in the core region of hepatitis C virus genotype 1b (HCV 1b) are a predictor of the non-virological response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy. The aim of our study was to develop quantitative real-time reverse transcription polymerase chain reaction (qPCR) assays to quantify wild-type (70 W) and mutant (70 M) strains of HCV 1b. METHODS: We used the TaqMan system to quantify strains 70 W and 70 M. Codon 70 in the HCV 1b core region can be either CGN or CAN, therefore degenerate TaqMan minor groove binder (MGB) probes with inosine were used. We determined detection limits, sensitivity and specificity of the methods developed. Direct sequencing and cloning of the HCV core region were used to confirm the reliability of our new system. Serum samples from 138 Chinese patients infected with HCV 1b were examined with the system we developed and compared with results obtained from the Roche TaqMan RT-PCR HCV RNA quantitation system. RESULTS: Degenerate MGB probes were able to clearly distinguish 70 W from 70 M. The detection limit was 103 copies/mL. Cross-reactivity tests confirmed the specificity of our method. Our system can effectively quantify 70 W and 70 M for 99.6% of patients with HCV 1b. Further tests involving cloning and sequencing confirmed the reliability of our system. CONCLUSIONS: We developed an assay system using degenerate TaqMan MGB probes with inosine to quantify wild-type and mutant viral RNAs of the HCV 1b core region at aa 70. Our developed assay system had high levels of sensitivity and accuracy, and could prove useful in investigating dynamic changes during PEG-IFN/RBV therapy to assess virological responses. PMID- 25128408 TI - Multidimensional complexities of filariasis control in an era of large-scale mass drug administration programmes: a can of worms. AB - The impact of control and elimination programmes by mass drug administration (MDA) targeting onchocerciasis and lymphatic filariasis (LF) in sub-Saharan Africa over the last two decades has resulted in significantly reduced prevalence and intensity of infection, with some areas interrupting transmission. However, given that these infections are often co-endemic and the drugs (either ivermectin alone or combined with albendazole) also impact on soil transmitted helminths (STH), the importance of this, in terms of reaching the global goals has not been assessed. The additional problem posed by Loa loa, where ivermectin cannot be safely administered due to the risk of serious adverse events compounds this situation and has left populations drug naive and an alternative strategy to eliminate LF is yet to be initiated at scale. Here, we present a series of operational research questions, which must be addressed if the effectiveness of integrated control of filarial and helminth infections is to be understood for the endgame. This is particularly important in the diverse and dynamic epidemiological landscape, which has emerged as a result of the long-term large scale mass drug administration (or not). There is a need for a more holistic approach to address these questions. Different programmes should examine this increased complexity, given that MDA has multiple impacts, drugs are given over different periods, and programmes have different individual targets. PMID- 25128409 TI - Unconstrained snoring detection using a smartphone during ordinary sleep. AB - BACKGROUND: Snoring can be a representative symptom of a sleep disorder, and thus snoring detection is quite important to improving the quality of an individual's daily life. The purpose of this research is to develop an unconstrained snoring detection technique that can be integrated into a smartphone application. In contrast with previous studies, we developed a practical technique for snoring detection during ordinary sleep by using the built-in sound recording system of a smartphone, and the recording was carried out in a standard private bedroom. METHOD: The experimental protocol was designed to include a variety of actions that frequently produce noise (including coughing, playing music, talking, rining an alarm, opening/closing doors, running a fan, playing the radio, and walking) in order to accurately recreate the actual circumstances during sleep. The sound data were recorded for 10 individuals during actual sleep. In total, 44 snoring data sets and 75 noise datasets were acquired. The algorithm uses formant analysis to examine sound features according to the frequency and magnitude. Then, a quadratic classifier is used to distinguish snoring from non-snoring noises. Ten-fold cross validation was used to evaluate the developed snoring detection methods, and validation was repeated 100 times randomly to improve statistical effectiveness. RESULTS: The overall results showed that the proposed method is competitive with those from previous research. The proposed method presented 95.07% accuracy, 98.58% sensitivity, 94.62% specificity, and 70.38% positive predictivity. CONCLUSION: Though there was a relatively high false positive rate, the results show the possibility for ubiquitous personal snoring detection through a smartphone application that takes into account data from normally occurring noises without training using preexisting data. PMID- 25128411 TI - Can a tailored exercise and home hazard reduction program reduce the rate of falls in community dwelling older people with cognitive impairment: protocol paper for the i-FOCIS randomised controlled trial. AB - BACKGROUND: The rate of falls in community dwelling older people with cognitive impairment (CI) is twice that of a cognitively intact population, with almost two thirds of people with CI falling annually. Studies indicate that exercise involving balance and/or a home hazard reduction program are effective in preventing falls in cognitively intact older people. However the potential benefit of these interventions in reducing falls in people with CI has not been established.This randomised controlled trial will determine whether a tailored exercise and home hazard reduction program can reduce the rate of falls in community dwelling older people with CI. We will determine whether the intervention has beneficial effects on a range of physical and psychological outcome measures as well as quality of life of participants and their carers. A health economic analysis examining the cost and potential benefits of the program will also be undertaken. METHODS AND DESIGN: Three hundred and sixty people aged 65 years or older living in the community with CI will be recruited to participate in the trial. Each will have an identifiable carer with a minimum of 3.5 hours of face to face contact each week.Participants will undergo an assessment at baseline with retests at 6 and 12 months. Participants allocated to the intervention group will participate in an exercise and home hazard reduction program tailored to their cognitive and physical abilities.The primary outcome measure will be the rate of falls which will be measured using monthly falls calendars. Secondary outcome measures will include the risk of falling, quality of life, measures of physical and cognitive function, fear of falling and planned and unplanned use of health services. Carers will be followed up to determine carer burden, coping strategies and quality of life. DISCUSSION: The study will determine the impact of this tailored intervention in reducing the rate of falls in community dwelling older people with CI as well as the cost-effectiveness and adherence to the program. The results will have direct implications for the design and implementation of interventions for this high-risk group of older people. TRIAL REGISTRATION: The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry - ACTRN12614000603617. PMID- 25128410 TI - Activated microglia contribute to neuronal apoptosis in Toxoplasmic encephalitis. AB - BACKGROUND: A plethora of evidence shows that activated microglia play a critical role in the pathogenesis of the central nervous system (CNS). Toxoplasmic encephalitis (TE) frequently occurs in HIV/AIDS patients. However, knowledge remains limited on the contributions of activated microglia to the pathogenesis of TE. METHODS: A murine model of reactivated encephalitis was generated in a latent infection with Toxoplasma gondii induced by cyclophosphamide. The neuronal apoptosis in the CNS and the profile of pro-inflammatory cytokines were assayed in both in vitro and in vivo experiments. RESULTS: Microglial cells were found to be activated in the cortex and hippocampus in the brain tissues of mice. The in vivo expression of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) were up-regulated in TE mice, and accordingly, the neuronal apoptosis was significantly increased. The results were positively correlated with those of the in vitro experiments. Additionally,apoptosis of the mouse neuroblastoma type Neuro2a (N2a) remarkably increased when the N2a was co-cultured in transwell with microglial cells and Toxoplasma tachyzoites. Both in vivo and in vitro experiments showed that minocycline (a microglia inhibitor) treatment notably reduced microglial activation and neuronal apoptosis. CONCLUSIONS: Activated microglia contribute to neuronal apoptosis in TE and inhibition of microglia activation might represent a novel therapeutic strategy of TE. PMID- 25128412 TI - Barriers to sight impairment certification in the UK: the example of a population with diabetes in East London. AB - BACKGROUND: This study assessed the barriers to sight impairment certification in the East London Borough of Tower Hamlets amongst patients attending the Diabetic Retinopathy Screening Service (DRSS). METHODS: All patients who attended DRSS between 1stApril 2009 and 31st of March 2010 and whose recorded best corrected visual acuity (BCVA) at DRSS fulfilled the requirements for sight impairment in the UK were included. An additional 24 patients whose general practitioners (GPs) reported them to be certified blind due to no perception of light (NPL) vision were re-examined to ascertain the reason for certification, and their potential social and visual aids needs. RESULTS: 78 patients were identified with certifiable vision and were reviewed: 10 deceased in the preceding 12 months; 60 were not known to be certified. Of these, 57 attended further assessment, 27 were found to have non-certifiable vision, 9 were referred for further interventions, 9 were certified and 9 were found to be eligible, but declined certification. Five patients were registered due to diabetic eye disease.Of those 24 reported by the GP of NPL vision, only 4 had true NPL, the rest had usable vision. Only two of them were certified blind due to diabetes. CONCLUSIONS: Our data shows that sight certification in patients with diabetes might be underestimated and these patients often have non-diabetes related visual loss. We propose that data on certifiable visual impairment could serve, along with existing certification databases, as a resource for quality of care standards assessment and service provision for patients with diabetes. PMID- 25128413 TI - Change in abortion services after implementation of a restrictive law in Texas. AB - OBJECTIVES: In 2013, Texas passed omnibus legislation restricting abortion services. Provisions restricting medical abortion, banning most procedures after 20 weeks and requiring physicians to have hospital-admitting privileges were enforced in November 2013; by September 2014, abortion facilities must meet the requirements of ambulatory surgical centers (ASCs). We aimed to rapidly assess the change in abortion services after the first three provisions went into effect. STUDY DESIGN: We requested information from all licensed Texas abortion facilities on abortions performed between November 2012 and April 2014, including the abortion method and gestational age (< 12 weeks vs. >= 12 weeks). RESULTS: In May 2013, there were 41 facilities providing abortion in Texas; this decreased to 22 in November 2013. Both clinics closed in the Rio Grande Valley, and all but one closed in West Texas. Comparing November 2012-April 2013 to November 2013 April 2014, there was a 13% decrease in the abortion rate (from 12.9 to 11.2 abortions/1000 women age 15-44). Medical abortion decreased by 70%, from 28.1% of all abortions in the earlier period to 9.7% after November 2013 (p<0.001). Second trimester abortion increased from 13.5% to 13.9% of all abortions (p<0.001). Only 22% of abortions were performed in the state's six ASCs. CONCLUSIONS: The closure of clinics and restrictions on medical abortion in Texas appear to be associated with a decline in the in-state abortion rate and a marked decrease in the number of medical abortions. IMPLICATIONS: Supply-side restrictions on abortion - especially restrictions on medical abortion - can have a profound impact on access to services. Access to abortion care will become even further restricted in Texas when the ASC requirement goes into effect in 2014. PMID- 25128414 TI - Management of the open abdomen using vacuum-assisted wound closure and mesh mediated fascial traction. AB - BACKGROUND: The open abdomen has become an accepted treatment option of critically ill patients with severe intra-abdominal conditions. Fascial closure is a particular challenge in patients with peritonitis. This study investigates whether fascial closure rates can be increased in peritonitis patients by using an algorithm that combines vacuum-assisted wound closure and mesh-mediated fascial traction. Moreover, fascial closure rates for patients with peritonitis, trauma or abdominal compartment system (ACS) are compared. METHODS: Data were collected prospectively from all patients who underwent open abdomen management at our institution from 2006 to 2012. All patients were treated under a standardised algorithm that combines vacuum-assisted closure and mesh placement at the fascial level. RESULTS: During the study period, 53 patients (mean age 53 years) underwent open abdomen management for a mean duration of 15 days. Indications for leaving the abdomen open were peritonitis (51 %), trauma (26 %), and ACS or abdominal wall dehiscence (23 %). The fascial closure rate was 79 % in an intention-to-treat analysis and 89 % in a per-protocol analysis. Mortality was 13 %. No patient developed an enteroatmospheric fistula or abdominal wall dehiscence after closure. The mean duration of treatment was significantly longer in peritonitis patients (20 days) than in patients without peritonitis (10 days) (p = 0.03). There were no significant differences in fascial closure rates between patients with peritonitis (87 %), trauma (85 %), and ACS or abdominal wall dehiscence (100 %) (p = 0.647). CONCLUSIONS: Regardless of the underlying pathology, high fascial closure rates can be achieved using a combination of vacuum-assisted closure and mesh-mediated fascial traction. PMID- 25128415 TI - Heteronormativity and sexual partnering among bisexual Latino men. AB - Our analyses address the question of how bisexual Latino men organize their sexual partnerships. Heteronormativity can be understood as the set of social norms and normative structures that guide sexual partnering among men and women. We provide descriptive statistics to describe bisexual Latino men's sexual partnerships. Logistic and linear regression modeling were used to explore bivariate and multivariate relationships. Of our total sample (N = 142), 41.6 % had unprotected vaginal intercourse 2 months prior to the interview; 21.8 % had unprotected anal intercourse with female partners; 37.5 % had unprotected insertive anal intercourse with male partners; and 22.5 % had unprotected receptive anal intercourse with male partners. In our multivariate model, machismo was directly associated with meeting female partners through formal spaces (workplace, school, and/or church), but inversely associated with meeting male partners in formal spaces. Machismo was positively associated with meeting male sex partners through social networks (i.e., friendship and kinship networks). The more comfortable men were with homosexuality the less likely they were to meet men online and the more likely they were to meet men through social networks of friends and kinship. Interventions to reduce sexually transmitted diseases that target bisexual behavior as an epidemiological "bridge" of transmission from homosexual to heterosexual networks might very well benefit from a more complex understanding of how Latino bisexuality is patterned. Thus, this exploratory analysis might lead to a rethinking of how to address risk and vulnerability among Latino bisexual men and their sexual networks. PMID- 25128417 TI - Mutations in the 3c and 7b genes of feline coronavirus in spontaneously affected FIP cats. AB - Feline infectious peritonitis (FIP) is the most frequent lethal infectious disease in cats. However, understanding of FIP pathogenesis is still incomplete. Mutations in the ORF 3c/ORF 7b genes are proposed to play a role in the occurrence of the fatal FIPV biotype. Here, we investigated 282 tissue specimens from 28 cats that succumbed to FIP. Within one cat, viral sequences from different organs were similar or identical, whereas greater discrepancies were found comparing sequences from various cats. Eleven of the cats exhibited deletions in the 3c gene, resulting in truncated amino acid sequences. The 7b gene was affected by deletions only in one cat. In three of the FIP cats, coronavirus isolates with both intact 3c genes as well as 7b genes of full length could also be detected. Thus, deletions or stop codons in the 3c sequence seem to be a frequent but not compelling feature of FIPVs. PMID- 25128416 TI - Effect of human leukocyte antigen-C and -DQ matching on pediatric heart transplant graft survival. AB - BACKGROUND: A higher degree of human leukocyte antigen (HLA) matching at the A, B, and DR loci has been associated with improved long-term survival after pediatric heart transplantation in multiple International Society for Heart and Lung Transplantation registry reports. The aim of this study was to investigate the association of HLA matching at the C and DQ loci with pediatric graft survival. METHODS: The United Network of Organ Sharing database was queried for isolated heart transplants that occurred from 1988 to 2012 with a recipient age of 17 or younger and at least 1 postoperative follow-up encounter. When HLA matching at the C or DQ loci were analyzed, only transplants with complete typing of donor and recipient at the respective loci were included. Transplants were divided into patients with at least 1 match at the C locus (C-match) vs no match (C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no). Primary outcome was graft loss. Univariate analysis was performed with the log rank test. Cox regression analysis was performed with the following patient factors included in the model: recipient age, ischemic time; recipient on ventilator, extracorporeal membrane oxygenation, ventricular assist device, or inotropes at transplant; recipient serum bilirubin and creatinine closest to transplant, ratio of donor weight to recipient weight, underlying cardiac diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and DR loci. RESULTS: Complete typing at the C locus occurred in 2,429 of 4,731 transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731 transplants (74%). Patient factors were similar in C-match and C-no, except for year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year 2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%, respectively; p < 0.01). Matching at the C locus was not associated with a decreased risk of graft loss (median graft survival: 13.1 years [95% confidence interval {CI}, 11.5-14.8] in C-no vs 15.1 years [95% CI, 13.5-16.6) in C-match, p = 0.44 log-rank; hazard ratio, 0.93; 95% CI, 0.76-1.15; p = 0.52). DQ-match did not differ from DQ-no in any of the analyzed patient factors, except DQ-match was more likely to have high degree of matching at the A, B, and DR loci vs DQ-no (9.8% vs 3.2%, p < 0.01). Matching at the DQ locus was not associated with decreased risk of graft loss (median graft survival: DQ-no, 13.1 years [95% CI, 11.7-14.6) vs DQ-match, 13.0 years [95% CI, 11.4-14.6], p = 0.80, log-rank; hazard ratio, 0.95; 95% CI, 0.81-1.1; p = 0.51. CONCLUSIONS: Complete typing at the C locus of both donor and recipient occurs less often then typing at the DQ locus. A higher degree of donor-recipient HLA matching at the C locus or the DQ locus appears not to confer any graft survival advantage. PMID- 25128418 TI - Involvement of glucagon-like peptide 1 in the glucose homeostasis regulation in obese and pituitary-dependent hyperadrenocorticism affected dogs. AB - The incretin glucagon-like peptide 1 (GLP-1) enhances insulin secretion. The aim of this study was to assess GLP-1, glucose and insulin concentrations, Homeostatic Model Assessment (HOMA insulin sensitivity and HOMA beta-cell function) in dogs with pituitary-dependent hyperadrenocorticism (PDH), and compare these values with those in normal and obese dogs. The Oral Glucose Tolerance Test was performed and the glucose, GLP-1 and insulin concentrations were evaluated at baseline, and after 15, 30, 60 and 120 minutes. Both basal concentration and those corresponding to the subsequent times, for glucose, GLP-1 and insulin, were statistically elevated in PDH dogs compared to the other groups. Insulin followed a similar behaviour together with variations of GLP-1. HOMA insulin sensitivity was statistically decreased and HOMA beta-cell function increased in dogs with PDH. The higher concentrations of GLP-1 in PDH could play an important role in the impairment of pancreatic beta-cells thus predisposing to diabetes mellitus. PMID- 25128419 TI - Increase of multidrug efflux pump expression in fluoroquinolone-resistant Salmonella mutants induced by ciprofloxacin selective pressure. AB - Multidrug-resistant foodborne pathogens are a leading public health concern, as antimicrobial resistance can lead to therapeutic failure. In this study, a ciprofloxacin-susceptible Salmonella Istanbul (Sal10-FC-KU12) was isolated from chicken meat obtained from a market in Korea to induce ciprofloxacin-resistant mutants (SalML, SalMM, and SalMH). Minimum inhibitory concentrations (MICs) of 12 antibiotics were measured in the presence or absence of an efflux pump inhibitor. Expression levels of efflux pump-related genes (acrB, acrF, marA, ramA, rob, and soxS) were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Elevated MICs for the derived mutants were shown to result from the action of the efflux pump, with increased expression of marA, ramA, and acrB compared with the wild-type strain. The results of this study suggest that continued use of ciprofloxacin might induce the emergence of Salmonella mutants resistant not only to fluoroquinolones, but also to several other classes of antimicrobials. PMID- 25128420 TI - Darpp-32 and t-Darpp are differentially expressed in normal and malignant mouse mammary tissue. AB - BACKGROUND: Darpp-32 and t-Darpp are expressed in several forms of breast cancer. Both are transcribed from the gene PPP1R1B via alternative promoters. In humans, Darpp-32 is expressed in both normal and malignant breast tissue, whereas t-Darpp has only been found in malignant breast tissue. The exact biological functions of these proteins in the breast are not known. Although Darpp-32 is a well known regulator of neurotransmission, its role in other tissues and in cancer is less well understood. t-Darpp is known to increase cellular growth, inhibit apoptosis and contribute to acquired drug resistance. The use of transgenic mouse mammary tumor models to study Darpp-32 and t-Darpp in breast cancer in vivo has been limited by a lack of knowledge regarding t-Darpp expression in mice, in both normal and malignant tissue. METHODS: We used RT-PCR and Western analysis to investigate Darpp-32 and t-Darpp levels in normal and malignant mouse mammary tissue. To determine if Darpp-32 and t-Darpp play a direct role in mammary tumor development, Ppp1r1b gene knockout mice and wild-type mice were crossed with a mouse mammary tumor model. Tumor growth and metastasis were examined. Differences between groups were determined by the two-tailed Student's t-test. RESULTS: We found that Darpp-32 was expressed in normal mouse mammary tissue and in some breast tumors, whereas t-Darpp was found exclusively in tumors, with t-Darpp usually expressed at equal or higher levels than Darpp-32. Ppp1r1b knockout in MMTV-PyMT transgenic tumor mice resulted in a decrease in tumor growth. CONCLUSIONS: The shift in expression from Darpp-32 to t-Darpp during mouse mammary tumorigenesis is reminiscent of the expression patterns observed in humans and is consistent with a role for t-Darpp in promoting cell growth and Darpp-32 in inhibiting cell growth. Decreased tumor growth in Ppp1r1b knockout mice also suggests that t-Darpp plays a direct role, predominant to Darpp-32, in mammary tumor development. These results indicate that transgenic mouse mammary tumor models might be valuable tools for future investigation of Darpp-32 and t Darpp in breast cancer. PMID- 25128421 TI - Danish emergency nurses' attitudes towards self-harm - a cross-sectional study. AB - AIM: The aim of this study was to examine Danish emergency nurses' attitudes toward people hospitalized after an acetaminophen poisoning. Furthermore, the study examined the relationship between attitudes and factors such as age, gender, and education on self-harm. METHODS: A cross-sectional design was applied. Nurses from seven emergency departments (EDs) in a region in Denmark were asked to complete the Danish version of Attitudes towards Deliberate Self Harm Questionnaire (ADSHQ). RESULTS: Of the 254 eligible nurses working in the ED, 122 returned the questionnaires, leaving the response rate at 48%. Results show that the emergency nurses generally held positive attitudes toward patients with acetaminophen poisoning. Nurses with longer ED experience held more positive attitudes, and women scored significantly higher than men on the whole scale. Only 19% of the respondents had received education on self-harm, and this education seems to produce more positive attitudes and a greater self-efficacy in relation to managing the patient group. CONCLUSION: Nurses working in the ED generally hold positive attitudes toward patients with acetaminophen poisoning. It is suggested that education on self-harm is a worthwhile endeavor with the potential to strengthen and improve attitudes, for the benefit of both the nurses and the patients. PMID- 25128422 TI - Coptis chinensis alkaloids exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating C/EBP-alpha and PPAR-gamma. AB - Obesity is a complex, multifactorial, and chronic disease that increases the risk for type 2 diabetes, coronary heart disease and hypertension, and has become a major worldwide health problem. Developing novel anti-obesity drugs from natural products is a promising solution to the global health problem of obesity. While screening anti-obesity potentials of natural products, the methanol extract of the rhizome of Coptis chinensis (Coptidis Rhizoma) was found to significantly inhibit adipocyte differentiation and lipid contents in 3T3-L1 cells, as assessed by Oil-Red O staining. Five known alkaloids, berberine, epiberberine, coptisine, palmatine, and magnoflorine, were isolated from the n-BuOH fraction of the methanol extract of Coptidis Rhizoma. We determined the chemical structure of these alkaloids through comparisons of published nuclear magnetic resonance (NMR) spectral data. Furthermore, we screened these alkaloids for their ability to inhibit adipogenesis over a range of concentrations (12.5-50 MUM). All five Coptidis Rhizoma alkaloids significantly inhibited lipid accumulation in 3T3-L1 cells without affecting cell viability in a concentration dependent manner. In addition, the five alkaloids significantly reduced the expression levels of several adipocyte marker genes including proliferator activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP-alpha). In the present study, we found that the isolated alkaloids inhibited adipogenesis in a dose-dependent manner in 3T3-L1 cells; this inhibition was attributed to their abilities to downregulate the protein levels of the adipocyte marker proteins PPAR-gamma and C/EBP-alpha. Thus, these results suggest that Coptidis Rhizoma extract and its isolated alkaloids may be of therapeutic interest with respect to the treatment of obesity. PMID- 25128423 TI - Cytotoxic and anti-inflammatory ent-kaurane diterpenoids from Isodon wikstroemioides. AB - Seven new ent-kaurane diterpenoids, isowikstroemins A-G (1-7), were isolated from EtOAc extracts of the aerial parts of Isodon wikstroemioides. Their structures were elucidated by extensive spectroscopic analysis. The isolates were evaluated for their cytotoxicity against five human tumor cell lines, and compounds 1-4 exhibited significant activity with IC50 values ranging from 0.9 to 7.0 MUM. In addition, compounds 1, 2, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. PMID- 25128424 TI - The cytotoxic activities of cardiac glycosides from Streptocaulon juventas and the structure-activity relationships. AB - A series of cardiac glycosides were isolated and identified from the anti-tumor fraction of the root of Streptocaulon juventas in previous studies. In the present research, the cytotoxic activities of the 43 cardiac glycosides on three cell lines, human lung A549 adenocarcinoma cell, large cell lung cancer NCI-H460 cell and normal human fetal lung fibroblast MRC-5 cell, were evaluated in vitro. Most of the tested compounds showed potent inhibitory activities toward the three cell lines. Then, the structure-activity relationships were discussed in detail. It was indicated that hydroxyl and acetyl groups at C-16 increased the activity, whereas hydroxyl group at C-1 and C-5 can both increase and decrease the activity. Two glucosyl groups which were connected by C1'->C6' showed better inhibitory activity against cancer cell lines, while the C1'->C4' connection showed stronger inhibitory activity against the normal cell line. Also, this is the first report that the activities of these compounds exhibited different variation trends between A549 and NCI-H460 cell lines, which indicated that these compounds could selectively inhibit the cell growth. The results would lay a foundation for further research on new anti-tumor drug development. PMID- 25128425 TI - The therapeutic effects of EGCG on vitiligo. AB - Epigallocatechin-3-gallate (EGCG) is one of the main chemical constituents of green tea, which has been used as an important traditional Chinese medicine. Green tea has anti-inflammatory, anti-oxidant, and immunomodulatory properties. However, the effects of EGCG on vitiligo are not known. We assessed the role of EGCG in vitiligo induced by monobenzone in mice. We demonstrated that EGCG: delayed the time of depigmentation; reduced the prevalence of depigmentation; and decreased the area of depigmentation. Examination of depigmented skin treated with EGCG by reflectance confocal microscopy suggested increased numbers of epidermal melanocytes and histologic examination showed decreased perilesional accumulation of CD8(+) T cells. To further investigate the mechanism of the anti inflammatory effects of EGCG, levels of inflammatory mediator tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-6 were tested by enzyme-linked immunosorbent assay. Serum cytokine levels were significantly decreased after administration of EGCG compared with the model group. These results suggested that EGCG may have protective effects against vitiligo, and that it could contribute to suppression of activation of CD8(+) T cells and inflammatory mediators. Based on these results, 5% EGCG was considered to be the most suitable concentration for treating vitiligo, and was used for further study. In addition, we investigated the gene-expression profile of this model in relation to EGCG. Using a 4*44K whole genome oligo microarray assay, 1264 down regulated genes and 1332 up-regulated genes were recorded in the 5% EGCG group compared with the model group, and selected genes were validated by real-time polymerase chain reaction. Our study demonstrated that EGCG administration was significantly associated with a decreased risk of vitiligo. EGCG could be a new preventive agent against vitiligo in the clinical setting. PMID- 25128426 TI - Chemical constituents of Morus alba L. and their inhibitory effect on 3T3-L1 preadipocyte proliferation and differentiation. AB - Mulberry leaf, an important traditional Chinese medicine, possesses many biological activities, including effects of anti-obesity. However, which constituents of mulberry leaf are responsible for its anti-adipogenic action is unclear. This study primarily investigated the chemical constituents from mulberry leaf and their bioactivity on the proliferation and differentiation of 3T3-L1 preadipocytes. A new flavane derivative, (2S)-4'-hydroxy-7-methoxy-8 prenylflavan (1), together with twelve known compounds including three flavanes (2-4), three chalcones (5-7), two flavones (8-9), two benzofurans (10-11) and two coumarin (12-13) was isolated from mulberry leaf. The structure of the new compound was elucidated by various spectroscopic methods including UV, HR-ESI-MS, (1)H and (13)C NMR and CD. The results of activity screening showed that compound 2, 6 and 7 inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. PMID- 25128427 TI - Penialidins A-C with strong antibacterial activities from Penicillium sp., an endophytic fungus harboring leaves of Garcinia nobilis. AB - Three new polyketides named penialidins A-C (1-3), along with one known compound, citromycetin (4), were isolated from an endophytic fungus, Penicillium sp., harbored in the leaves of the Cameroonian medicinal plant Garcinia nobilis. Their structures were elucidated by means of spectroscopic and spectrometric methods (NMR and HRMS(n)). The antibacterial efficacies of the new compounds (1-3) were tested against the clinically-important risk group 2 (RG2) bacterial strains of Staphylococcus aureus and Escherichia coli. The ecologically imposing strains of E. coli (RG1), Bacillus subtilis and Acinetobacter sp. BD4 were also included in the assay. Compound 3 exhibited pronounced activity against the clinically relevant S. aureus as well as against B. subtilis comparable to that of the reference standard (streptomycin). Compound 2 was also highly-active against S. aureus. By comparing the structures of the three new compounds (1-3), it was revealed that altering the substitutions at C-10 and C-2 can significantly increase the antibacterial activity of 1. PMID- 25128428 TI - Sesterterpenoids and other constituents from Salvia lachnocalyx Hedge. AB - Three new sesterterpene lactones, lachnocalyxolide A-C [1, 2, and 3 (as epimeric pair)] together with nine known compounds, including two sesterterpenoids, three flavonoids, two steroidal compounds, one nor diterpenoid and one triterpenoid, were isolated from the acetone extract of the aerial parts of Salvia lachnocalyx Hedge. Their structures were elucidated on the basis of extensive spectroscopic data, including 1D and 2D NMR spectra, as well as HR-ESI-MS. Compounds 1, 2, 4 and 5 were also tested for their inhibitory activity toward MCF-7 and HeLa cell lines. PMID- 25128429 TI - Association between parental guilt and oral health problems in preschool children: a hierarchical approach. AB - BACKGROUND: Dental caries and traumatic dental injury (TDI) can play an important role in the emergence of parental guilt, since parents feel responsible for their child's health. The aim of the present study was to evaluate the influence of oral health problems among preschool children on parental guilt. METHODS: A preschool-based, cross-sectional study was carried out with 832 preschool children between three and five years of age in the city of Campina Grande, Brazil. Parents/caregivers answered the Brazilian version of the Early Childhood Oral Health Impact Scale (B-ECOHIS). The item "parental guilt" was the dependent variable. Questionnaires addressing socio-demographic variables (child's sex, child's age, parent's/caregiver's age, mother's schooling, type of preschool and household income), history of toothache and health perceptions (general and oral) were also administered. Clinical exams for dental caries and TDI were performed by three dentists who had undergone a training and calibration exercise (Kappa: 0.85-0.90). Poisson hierarchical regression was used to determine the significance of associations between parental guilt and oral health problems (alpha = 5%). The multivariate model was carried out on three levels using a hierarchical approach from distal to proximal determinants: 1) socio-demographic aspects; 2) health perceptions; and 3) oral health problems. RESULTS: The frequency of parental guilt was 22.8%. The following variables were significantly associated with parental guilt: parental perception of child's oral health as poor (PR = 2.010; 95% CI: 1.502-2.688), history of toothache (PR = 2.344; 95% CI: 1.755-3.130), cavitated lesions (PR = 2.002; 95% CI: 1.388-2.887), avulsion/luxation (PR = 2.029; 95% CI: 1.141-3.610) and tooth discoloration (PR = 1.540; 95% CI: 1.169-2.028). CONCLUSION: Based on the present findings, parental guilt increases with the occurrence of oral health problems that require treatment, such as dental caries and TDI of greater severity. Parental perceptions of poor oral health in their children and history of toothache were predictors of greater feelings of parental guilt. PMID- 25128430 TI - Absence of an association between anti-Ro antibodies and prolonged QTc interval in systemic sclerosis: a multicenter study of 689 patients. AB - OBJECTIVE: To examine the association between anti-Ro antibodies, namely anti Ro60/SS-A and anti-Ro52/TRIM21, together and separately, and a prolonged QT interval corrected for heart rate (QTc) in systemic sclerosis (SSc) patients. METHODS: A total of 689 SSc patients enrolled in a multicenter cohort study underwent a 12-lead resting EKG at baseline. The QTc interval was measured, and a QTc >= 440ms was considered prolonged. Detailed clinical data and sera of these patients were collected and positivity for anti-Ro60/SS-A and anti-Ro52/TRIM21 antibodies was determined using an addressable laser bead immunoassay (ALBIA). RESULTS: QTc prolongation was common in this SSc cohort (25%). In a univariate analysis, Ro antibodies, together or separately, were not associated with prolongation of the QTc interval [mean difference in QTc in anti-Ro antibody positive versus negative subjects was -2.2ms (p = 0.5748), in anti-Ro60/SS-A antibody positive versus negative subjects was 1.3ms (p = 0.8616), and in anti Ro52/TRIM21 antibody positive versus negative subjects was -3.3ms (p = 0.4106)]. In a multivariate logistic regression analysis adjusting for possible confounders, there was no association between prolonged QTc and anti-Ro antibodies [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.45, 1.22], anti-Ro60/SS-A antibodies (OR = 1.57, 95% CI: 0.72, 3.41), and anti-Ro52/TRIM21 antibodies (OR = 0.76, 95% CI: 0.46, 1.26). However, in both univariate and multivariate analyses, QTc prolongation was associated with longer disease duration, greater disease severity, and the presence of anti-RNA polymerase III antibodies. CONCLUSIONS: QTc prolongation is common in SSc, although anti-Ro antibodies do not seem to be associated with it as is the case in systemic lupus erythematosus. The reasons for this difference as well as the cause of abnormalities in cardiac repolarization in SSc will require additional studies. PMID- 25128431 TI - Dissociating the influence of response selection and task anticipation on corticospinal suppression during response preparation. AB - Motor behavior requires selecting between potential actions. The role of inhibition in response selection has frequently been examined in tasks in which participants are engaged in some advance preparation prior to the presentation of an imperative signal. Under such conditions, inhibition could be related to processes associated with response selection, or to more general inhibitory processes that are engaged in high states of anticipation. In Experiment 1, we manipulated the degree of anticipatory preparation. Participants performed a choice reaction time task that required choosing between a movement of the left or right index finger, and used transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in the left hand agonist. In high anticipation blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in low anticipation blocks, there was no cue and participants were required to divide their attention between two tasks to further reduce anticipation. MEPs were substantially reduced before the imperative signal in high anticipation blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before the imperative signal but showed a marked suppression right after the onset of the imperative. This effect occurred regardless of whether the imperative had signalled a left or right hand response. After this initial inhibition, left MEPs increased when the left hand was selected and remained suppressed when the right hand was selected. We obtained similar results in Experiment 2 except that the persistent left MEP suppression when the left hand was not selected was attenuated when the alternative response involved a non-homologous effector (right foot). These results indicate that, even in the absence of an anticipatory period, inhibitory mechanisms are engaged during response selection, possibly to prevent the occurrence of premature and inappropriate responses during a competitive selection process. PMID- 25128434 TI - Pilot randomized evaluation of publically available concussion education materials: evidence of a possible negative effect. AB - Many states and sports leagues are instituting concussion policies aimed at reducing risk of morbidity and mortality; many include mandates about the provision of concussion education to youth athletes. However, there is limited evidence if educational materials provided under these typically vague mandates are in fact effective in changing concussion risk-related behavior or any cognition predictive of risk-related behavior. The purpose of this pilot randomized controlled study was to conduct a theory-driven evaluation of three publically available concussion education materials: two videos and one informational handout. Participants were 256 late adolescent males from 12 teams in a single league of ice hockey competition in the United States. Randomization of educational condition occurred at the team level. Written surveys assessing postimpact symptom reporting behavior, concussion knowledge, and concussion reporting cognitions were completed by participants immediately before receiving their educational intervention, 1 day after, and 1 month after. Results indicated no change in any measure over any time interval, with the exception of perceived underreporting norms. In one of the video conditions, perceived underreporting norms increased significantly 1 day after viewing the video. Possible content and viewing environment-related reasons for this increase are discussed. Across all conditions, perceived underreporting norms increased 1 month after intervention receipt, raising the possibility that late in the competitive season underreporting may be perceived as normative. The need for the development of theory-driven concussion education materials, drawing on best practices from health behavior scholars, is discussed. PMID- 25128433 TI - Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation. AB - Telomere length homeostasis is essential for the long-term survival of stem cells, and its set point determines the proliferative capacity of differentiated cell lineages by restricting the reservoir of telomeric repeats. Knockdown and overexpression studies in human tumor cells showed that the shelterin subunit TPP1 recruits telomerase to telomeres through a region termed the TEL patch. However, these studies do not resolve whether the TPP1 TEL patch is the only mechanism for telomerase recruitment and whether telomerase regulation studied in tumor cells is representative of nontransformed cells such as stem cells. Using genome engineering of human embryonic stem cells, which have physiological telomere length homeostasis, we establish that the TPP1 TEL patch is genetically essential for telomere elongation and thus long-term cell viability. Furthermore, genetic bypass, protein fusion, and intragenic complementation assays define two distinct additional mechanisms of TPP1 involvement in telomerase action at telomeres. We demonstrate that TPP1 provides an essential step of telomerase activation as well as feedback regulation of telomerase by telomere length, which is necessary to determine the appropriate telomere length set point in human embryonic stem cells. These studies reveal and resolve multiple TPP1 roles in telomere elongation and stem cell telomere length homeostasis. PMID- 25128435 TI - Resolution of genetic map expansion caused by excess heterozygosity in plant recombinant inbred populations. AB - Recombinant inbred populations of many plant species exhibit more heterozygosity than expected under the Mendelian model of segregation. This segregation distortion causes the overestimation of recombination frequencies and consequent genetic map expansion. Here we build upon existing genetic models of differential zygotic viability to model a heterozygote fitness term and calculate expected genotypic proportions in recombinant inbred populations propagated by selfing. We implement this model using the existing open-source genetic map construction code base for R/qtl to estimate recombination fractions. Finally, we show that accounting for excess heterozygosity in a sorghum recombinant inbred mapping population shrinks the genetic map by 213 cM (a 13% decrease corresponding to 4.26 fewer recombinations per meiosis). More accurate estimates of linkage benefit linkage-based analyses used in the identification and utilization of causal genetic variation. PMID- 25128436 TI - QTug.sau-3B is a major quantitative trait locus for wheat hexaploidization. AB - Meiotic nonreduction resulting in unreduced gametes is thought to be the predominant mechanism underlying allopolyploid formation in plants. Until now, however, its genetic base was largely unknown. The allohexaploid crop common wheat (Triticum aestivum L.), which originated from hybrids of T. turgidum L. with Aegilops tauschii Cosson, provides a model to address this issue. Our observations of meiosis in pollen mother cells from T. turgidum*Ae. tauschii hybrids indicated that first division restitution, which exhibited prolonged cell division during meiosis I, was responsible for unreduced gamete formation. A major quantitative trait locus (QTL) for this trait, named QTug.sau-3B, was detected on chromosome 3B in two T. turgidum*Ae. tauschii haploid populations. This QTL is situated between markers Xgwm285 and Xcfp1012 and covered a genetic distance of 1 cM in one population. QTug.sau-3B is a haploid-dependent QTL because it was not detected in doubled haploid populations. Comparative genome analysis indicated that this QTL was close to Ttam-3B, a collinear homolog of tam in wheat. Although the relationship between QTug.sau-3B and Ttam requires further study, high frequencies of unreduced gametes may be related to reduced expression of Ttam in wheat. PMID- 25128437 TI - Performance of the Cas9 nickase system in Drosophila melanogaster. AB - Recent studies of the Cas9/sgRNA system in Drosophila melanogaster genome editing have opened new opportunities to generate site-specific mutant collections in a high-throughput manner. However, off-target effects of the system are still a major concern when analyzing mutant phenotypes. Mutations converting Cas9 to a DNA nickase have great potential for reducing off-target effects in vitro. Here, we demonstrated that injection of two plasmids encoding neighboring offset sgRNAs into transgenic Cas9(D10A) nickase flies efficiently produces heritable indel mutants. We then determined the effective distance between the two sgRNA targets and their orientations that affected the ability of the sgRNA pairs to generate mutations when expressed in the transgenic nickase flies. Interestingly, Cas9 nickase greatly reduces the ability to generate mutants with one sgRNA, suggesting that the application of Cas9 nickase and sgRNA pairs can almost avoid off-target effects when generating indel mutants. Finally, a defined piwi mutant allele is generated with this system through homology-directed repair. However, Cas9(D10A) is not as effective as Cas9 in replacing the entire coding sequence of piwi with two sgRNAs. PMID- 25128432 TI - The construct of the multisensory temporal binding window and its dysregulation in developmental disabilities. AB - Behavior, perception and cognition are strongly shaped by the synthesis of information across the different sensory modalities. Such multisensory integration often results in performance and perceptual benefits that reflect the additional information conferred by having cues from multiple senses providing redundant or complementary information. The spatial and temporal relationships of these cues provide powerful statistical information about how these cues should be integrated or "bound" in order to create a unified perceptual representation. Much recent work has examined the temporal factors that are integral in multisensory processing, with many focused on the construct of the multisensory temporal binding window - the epoch of time within which stimuli from different modalities is likely to be integrated and perceptually bound. Emerging evidence suggests that this temporal window is altered in a series of neurodevelopmental disorders, including autism, dyslexia and schizophrenia. In addition to their role in sensory processing, these deficits in multisensory temporal function may play an important role in the perceptual and cognitive weaknesses that characterize these clinical disorders. Within this context, focus on improving the acuity of multisensory temporal function may have important implications for the amelioration of the "higher-order" deficits that serve as the defining features of these disorders. PMID- 25128439 TI - Uncovering zoonoses awareness in an emerging disease 'hotspot'. AB - Emerging infectious diseases from animals pose significant and increasing threats to human health; places of risk are simultaneously viewed as conservation and emerging disease 'hotspots'. The One World/One Health paradigm is an 'assemblage' discipline. Extensive research from the natural and social sciences, as well as public health have contributed to designing surveillance and response policy within the One World/One Health framework. However, little research has been undertaken that considers the lives of those who experience risk in hotspots on a daily basis. As a result, policymakers and practitioners are unable to fully comprehend the social and ecological processes that catalyze cross-species pathogen exchange. This study examined local populations' comprehension of zoonotic disease. From October 2008-May 2009 we collected data from people living on the periphery of Kibale National Park, in western Uganda. We administered a survey to 72 individuals and conducted semi-structured, in-depth interviews with 14 individuals. Results from the survey showed respondents had statistically significant awareness that transmission of diseases from animals was possible compared to those who did not think such transmission was possible (x(2) = 30.68, df = 1, p < 0.05). However, individual characteristics such as gender, occupation, location, and age were not significantly predictive of awareness. Both quantitative and qualitative data show local people are aware of zoonoses and provided biomedically accurate examples of possible infections and corresponding animal sources (e.g., worm infection from pigs and Ebola from primates). Qualitative data also revealed expectations about the role of the State in managing the prevention of zoonoses from wildlife. As a result of this research, we recommend meaningful discourse with people living at the frontlines of animal contact in emerging disease and conservation hotspots in order to develop informed and relevant zoonoses prevention practices that take into account local knowledge and perceptions. PMID- 25128438 TI - Widespread genomic incompatibilities in Caenorhabditis elegans. AB - In the Bateson-Dobzhansky-Muller (BDM) model of speciation, incompatibilities emerge from the deleterious interactions between alleles that are neutral or advantageous in the original genetic backgrounds, i.e., negative epistatic effects. Within species such interactions are responsible for outbreeding depression and F2 (hybrid) breakdown. We sought to identify BDM incompatibilities in the nematode Caenorhabditis elegans by looking for genomic regions that disrupt egg laying; a complex, highly regulated, and coordinated phenotype. Investigation of introgression lines and recombinant inbred lines derived from the isolates CB4856 and N2 uncovered multiple incompatibility quantitative trait loci (QTL). These QTL produce a synthetic egg-laying defective phenotype not seen in CB4856 and N2 nor in other wild isolates. For two of the QTL regions, results are inconsistent with a model of pairwise interaction between two loci, suggesting that the incompatibilities are a consequence of complex interactions between multiple loci. Analysis of additional life history traits indicates that the QTL regions identified in these screens are associated with effects on other traits such as lifespan and reproduction, suggesting that the incompatibilities are likely to be deleterious. Taken together, these results indicate that numerous BDM incompatibilities that could contribute to reproductive isolation can be detected and mapped within C. elegans. PMID- 25128440 TI - Direct costs associated with the management of progressive early onset scoliosis: estimations based on gold standard technique or with magnetically controlled growing rods. AB - BACKGROUND: The main disadvantage of the surgical management of early onset scoliosis (EOS) using conventional growing rods is the need for iterative surgical procedures during childhood. The emergence of an innovative device using distraction-based magnetically controlled growing rods (MCGR) provides the opportunity to avoid such surgeries and therefore to improve the patient's quality of life. HYPOTHESIS: Despite the high cost of MCGR and considering its potential impact in reducing hospital stays, the use of MCGR could reduce medical resource consumption in a long-term view in comparison to traditional growing rod (TGR). MATERIALS AND METHODS: A cost-simulation model was constructed to assess the incremental cost between the two strategies. The cost for each strategy was estimated based on probability of medical resource consumption determined from literature search as well as data from EOS patients treated in our centre. Some medical expenses were also estimated from expert interviews. The time horizon chosen was 4 years as from first surgical implantation. Costs were calculated in the perspective of the French sickness fund (using rates from year 2013) and were discounted by an annual rate of 4%. Sensitivity analyses were conducted to test model strength to various parameters. RESULTS: With a time horizon of 4 years, the estimated direct costs of TGR and MCGR strategies were 49,067 ? and 42,752 ?, respectively leading to an incremental costs of 6135 ? in favour of MCGR strategy. In the first case, costs were mainly represented by hospital stays expenses (83.9%) whereas in the other the cost of MCGR contributed to 59.5% of the total amount. In the univariate sensitivity analysis, the tariffs of hospital stays, the tariffs of the MCG, and the frequency of distraction surgeries were the parameters with the most important impact on incremental cost. DISCUSSION: MCGR is a recent and promising innovation in the management of severe EOS. Besides improving the quality of life, its use in the treatment of severe EOS is likely to be offset by lower costs of hospital stays. LEVEL OF EVIDENCE (WITH STUDY DESIGN): Level IV, economic and decision analyses, retrospective study. PMID- 25128441 TI - Epidemiology and outcomes in patients with severe sepsis admitted to the hospital wards. AB - PURPOSE: The purpose of this study was to detail the trajectory and outcomes of patients with severe sepsis admitted from the emergency department to a non intensive care unit (ICU) setting and identify risk factors associated with adverse outcomes. MATERIAL AND METHODS: This was a single-center retrospective cohort study conducted at a tertiary, academic hospital in the United States between 2005 and 2009. The primary outcome was a composite outcome of ICU transfer within 48 hours of admission and/or 28-day mortality. RESULTS: Of 1853 patients admitted with severe sepsis, 841 (45%) were admitted to a non-ICU setting, the rate increased over time (P < .001), and 12.5% of these patients were transferred to the ICU within 48 hours and/or died within 28 days. In multivariable models, age (P < .001), an oncology diagnosis (P < .001), and illness severity as measured by Acute Physiologic and Chronic Health Evaluation II (P = .04) and high (>=4 mmol/L) initial serum lactate levels (P = .005) were associated with the primary outcome. CONCLUSIONS: Patients presenting to the emergency department with severe sepsis were frequently admitted to a non-ICU setting, and the rate increased over time. Of 8 patients admitted to the hospital ward, one was transferred to the ICU within 48 hours and/or died within 28 days of admission. Factors present at admission were identified that were associated with adverse outcomes. PMID- 25128443 TI - Prostate pointers and pitfalls: the 10 most prevalent problems in prostate biopsy interpretation. AB - As small volumes of prostate cancer are being detected with ever-increasing frequency, the pathologist is challenged to make more diagnostically out of less. This photoessay explores ten diagnostic problems that are noted with regularity by a provider of second opinions in prostate biopsy interpretation. These include: suboptimal submission of prostate cores, atypia with small size of the focus of concern, cytologic ambiguity of the focus of concern, issues with ordering and interpreting immunostains, atypia arising with high-grade prostatic intraepithelial neoplasia, benign mimics of cancer, omitting mention of extraprostatic tumor extension or of Gleason pattern 5, not recognizing intraductal carcinoma, and the differential diagnosis of cancer of urothelial versus prostatic origin. PMID- 25128442 TI - Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery. AB - INTRODUCTION: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondrial DNA (mtDNA) under certain conditions, which is potently proinflammatory. We hypothesized that injury and orthopedic trauma surgery would induce NET production with mtDNA as a structural component. METHODS: Neutrophils were isolated 8 trauma patients requiring orthopedic surgery postinjury and up to 5 days postoperatively. Four healthy volunteers provided positive and negative controls. Total hip replacement patients acted as an uninjured surgical control group. Neutrophil extracellular traps were visualized with DNA (Hoechst 33342TM/Sytox Green/MitoSox/MitoTracker) stains using live cell fluorescence microscopy with downstream quantitative polymerase chain reaction analysis of DNA composition. RESULTS: Neutrophil extracellular traps were present after injury in all 8 trauma patients. They persisted for 5 days postoperatively. Delayed surgery resulted in NET resolution, but they reformed postoperatively. Total hip replacement patients developed NETs postoperatively, which resolved by day 5. Quantitative polymerase chain reaction analysis of NET-DNA composition revealed that NETs formed after injury and surgery were made of mtDNA with no detectable nuclear DNA component. CONCLUSIONS: Neutrophil extracellular traps formed after major trauma and subsequent surgery contain mtDNA and represent a novel marker of heightened innate immune activation. They could be considered when timing surgery after trauma to prevent systemic NET-induced inflammatory complications. PMID- 25128445 TI - Endogenous allergens in the regulatory assessment of genetically engineered crops. AB - A scientific approach to the assessment of foods derived from genetically engineered (GE) crops is critical to maintaining objectivity and public confidence in regulatory decisions. Principles developed at the international level support regulators and enable robust and transparent safety assessments. A comparison of key constituents in the GE crop with a suitable comparator is an important element of an assessment. In Europe, endogenous allergens would be included in the comparative analysis, however this approach has been hindered by technical limitations on the ability to accurately measure identified allergenic proteins. Over recent years, improved proteomic methods have enabled researchers to focus on major allergenic proteins in conventional food crops, as information on natural variability is largely lacking. Emerging data for soybean indicate that variability in levels of major allergens already in the food supply is broad. This raises questions about the biological interpretation of differences between a GE plant and its conventional counterpart, in particular, whether any conclusions about altered allergenicity could be inferred. This paper discusses the scientific justification for requiring proteomic analysis of endogenous allergens as part of the evaluation. Ongoing scientific review and corresponding international discussion are integral to ensuring that data requirements address legitimate risk assessment questions. PMID- 25128444 TI - Impact of prolapse meshes on the metabolism of vaginal extracellular matrix in rhesus macaque. AB - OBJECTIVE: The impact of polypropylene mesh implantation on vaginal collagen and elastin metabolism was analyzed using a nonhuman primate model to further delineate the mechanism of mesh induced complications. STUDY DESIGN: Forty-nine middle-aged parous rhesus macaques underwent surgical implantation of 3 synthetic meshes via sacrocolpopexy. Gynemesh PS (n = 12) (Ethicon, Somerville, NJ) and 2 lower-weight, higher-porosity, lower-stiffness meshes (UltraPro [n = 19] [Ethicon] and Restorelle [n = 8] [Coloplast, Minneapolis, MN]) were implanted, in which UltraPro was implanted with its blue orientation lines perpendicular (low stiffness direction, n = 11) and parallel (high stiffness direction, n = 8) to the longitudinal axis of the vagina. Sham-operated animals were used as controls (n = 10). Twelve weeks after surgery, the mesh-tissue complex was excised and analyzed. RESULTS: Relative to sham, Gynemesh PS had a negative impact on the metabolism of both collagen and elastin-favoring catabolic reactions, whereas UltraPro induced an increase only in elastin degradation. Restorelle had the least impact. As compared with sham, the degradation of collagen and elastin in the vagina implanted with Gynemesh PS was increased with a simultaneous increase in active matrix metalloproteinase (MMP)-1, -8, -13, and total MMP-2 and -9 (all P < .05). The degradation of elastin (tropoelastin and mature elastin) was increased in the UltraPro-implanted vagina with a concomitant increase of MMP-2, and -9 (all P < .05). Collagen subtype ratio III/I was increased in Gynemesh PS and UltraPro perpendicular groups (P < .05). CONCLUSION: Following implantation with the heavier, less porous, and stiffer mesh, Gynemesh PS, the degradation of vaginal collagen and elastin exceeded synthesis, most likely as a result of increased activity of MMPs, resulting in a structurally compromised tissue. PMID- 25128446 TI - Pediatric cochlear implant revision surgery and reimplantation: an analysis of 957 cases. AB - OBJECTIVE: In this study causes, risk factors, prevention strategies, diffuculties encountered during revision cochlear implant surgery, reimplantation in pediatric age group were evaluated. METHODS: Charts of 957 CI patients younger than 18 years of age implanted at Izmir Bozyaka Teaching and Research Hospital between 1998 and July 2012 and 18 referred CI complications at same age group were retrospectively evaluated. Revision and reimplantation surgeries were systematically reviewed. RESULTS: We encountered 26 surgical complications in 24 patients and 36 device related problems in 36 patients. Eighteen referred cases including 7 surgical complications and 11 device related problems were also evaluated. A total number of 80 complications were evaluated. In 11 cases conservative management was successful, 19 revision surgery was performed but we failed in 4 cases. We reimplanted 48 cases and 4 additional cases were implanted after failed revision surgery. Implant was extracted in one case. In one case we could implant the other side. Forty-six of reimplantations were done in one stage surgery, 5 cases required second stage surgery. CONCLUSIONS: Surgical complications and device related problems of cochlear implantation may be different in children and majority of them require revision surgery or reimplantation. Although surgical problems leading to revision surgery and reimplantation are expected to diminish by experience every center has to deal with device failures. Both revision surgery and reimplantation require extra care and it should be better carried out by experienced surgeons. Implant performances are expected to be comparable with primary implantations. PMID- 25128447 TI - Aided cortical response, speech intelligibility, consonant perception and functional performance of young children using conventional amplification or nonlinear frequency compression. AB - OBJECTIVE: The aim of this study was to compare conventional processing with nonlinear frequency compression (NLFC) in hearing aids for young children with bilateral hearing loss. METHODS: Sixty-four children aged between 2 and 7 years with bilateral hearing aids were recruited. Evaluations of cortical responses, speech intelligibility rating, consonant perception and functional performance were completed with the children wearing their personal hearing aids with conventional processing. The children were then refitted with new hearing aids with NLFC processing. Following a six-week familiarization period, they were evaluated again while using their hearing aids with NLFC activated. RESULTS: The mean speech intelligibility rating and the number of cortical responses present for /s/were significantly higher when children were using NLFC processing than conventional processing in their hearing aids (p<0.05). Parents judged the children's functional real life performance with the NLFC hearing aids to be similar or better than that with the children's own hearing aids in both quiet and noisy situations. The mean percent consonant score was higher with NLFC processing compared to conventional processing, but the difference did not reach the 5% significance level (p=0.056). An overall figure of merit (FOM) was calculated by averaging the standardized difference scores between processing schemes for all measures. Regression analysis revealed that, on average, greater advantage for NLFC processing was associated with poorer hearing at 4 kHz. CONCLUSIONS: Compared to conventional processing, the use of NLFC was, on average, effective in increasing audibility of /s/as measured by cortical evaluations, and higher ratings on speech intelligibility and functional performance in real life by parents. On average, greater benefits from NLFC processing was associated with poorer hearing at 4 kHz. PMID- 25128448 TI - Respiratory viruses are continuously detected in children with chronic tonsillitis throughout the year. AB - OBJECTIVE: To evaluate the oscillations on the viral detection in adenotonsillar tissues from patients with chronic adenotonsillar diseases as an indicia of the presence of persistent viral infections or acute subclinical infections. STUDY DESIGN: Cross-sectional prospective study. SETTING: Tertiary hospital. METHODS: The fluctuations of respiratory virus detection were compared to the major climatic variables during a two-year period using adenoids and palatine tonsils from 172 children with adenotonsillar hypertrophy and clinical evidence of obstructive sleep apnoea syndrome or recurrent adenotonsillitis, without symptoms of acute respiratory infection (ARI), by TaqMan real-time PCR. RESULTS: The rate of detection of at least one respiratory virus in adenotonsillar tissue was 87%. The most frequently detected viruses were human adenovirus in 52.8%, human enterovirus in 47.2%, human rhinovirus in 33.8%, human bocavirus in 31.1%, human metapneumovirus in 18.3% and human respiratory syncytial virus in 17.2%. Although increased detection of human enterovirus occurred in summer/autumn months, and there were summer nadirs of human respiratory syncytial virus in both years of the study, there was no obvious viral seasonality in contrast to reports with ARI patients in many regions of the world. CONCLUSION: Respiratory viruses are continuously highly detected during whole year, and without any clinical symptomatology, indicating that viral genome of some virus can persist in lymphoepithelial tissues of the upper respiratory tract. PMID- 25128449 TI - Prevalence and types of articulation errors in Saudi Arabic-speaking children with repaired cleft lip and palate. AB - OBJECTIVES: The purpose of this study was to assess prevalence and types of consonant production errors and phonological processes in Saudi Arabic-speaking children with repaired cleft lip and palate, and to determine the relationship between frequency of errors on one hand and the type of the cleft. Possible relationship between age, gender and frequency of errors was also investigated. METHODS: Eighty Saudi children with repaired cleft lip and palate aged 6-15 years (mean 6.7 years), underwent speech, language, and hearing evaluation. The diagnosis of articulation deficits was based on the results of an Arabic articulation test. Phonological processes were reported based on the productivity scale of a minimum 20% of occurrence. Diagnosis of nasality was based on a 5 point scale that reflects severity from 0 through 4. All participants underwent intraoral examination, informal language assessment, and hearing evaluation to assess their speech and language abilities. The Chi-Square test for independence was used to analyze the results of consonant production as a function of type of CLP and age. RESULTS: Out of 80 participants with CLP, 21 participants had normal articulation and resonance, 59 of participants (74%) showed speech abnormalities. Twenty-one of these 59 participants showed only articulation errors; 17 showed only hypernasality; and 21 showed both articulation and resonance deficits. CAs were observed in 20 participant. The productive phonological processes were consonant backing, final consonant deletion, gliding, and stopping. At age 6 and older, 37% of participants had persisting hearing loss. CONCLUSIONS: Despite early age at time of surgery (mean 6.7 months) for the studied CLP participants in this study, a substantial number of them demonstrated articulation errors and hypernasality. The results showed desirable findings for diverse languages. It is especially interesting to consider the prevalence of glottal stops and pharyngeal fricatives in a population for whom these sound are phonemic. PMID- 25128450 TI - Acetaminophen plus ibuprofen versus opioids for treatment of post-tonsillectomy pain in children. AB - OBJECTIVE: To determine the efficacy and safety of acetaminophen plus ibuprofen in treatment of post-tonsillectomy pain compared to acetaminophen plus opioids in children. STUDY DESIGN: Retrospective medical record review. SETTING: Tertiary care children's hospital between September 2012 and March 2013. SUBJECTS AND METHODS: All children undergoing total tonsillectomy (n=1065). Analysis included descriptive analysis, chi-square testing, and logistic regression controlling for age, diagnosis, trainee involvement, concurrent surgical procedures, and Coblator use for differences of outcomes: (1) post-operative bleeding, (2) emergency department (ED) visits for pain, dehydration, or bleeding, and (3) nurse phone calls from families. RESULTS: All patients received acetaminophen. Seventy-four percent received ibuprofen (n=783) and 26.5% did not receive ibuprofen (n=282). In the ibuprofen group, 32.2% received opioids (n=252). Over eight percent of children had post-operative hemorrhage of any amount reported (n=89). Forty-eight percent of these required operative intervention (n=43). Ibuprofen prescription did not impact post-operative bleeding; operative intervention for bleeding, ED visits, or nurse phone calls either on chi-squared or logistic regression testing. Increasing age was found to increase bleeding risk as well as the likelihood of visiting the ED or calling the clinic nurses. All patients with multiple bleeding episodes were in the ibuprofen group. CONCLUSION: Prescription of ibuprofen did not increase the risk of bleeding and did not increase the likelihood of a post-operative ED visit or nurse phone call. Ibuprofen prescription may possibly increase the risk of multiple bleeding episodes, but further prospective studies are needed. Increased age increases the risk of bleeding, ED visits, and nurse phone calls. PMID- 25128451 TI - Specificity of coliphages in evaluating marker efficacy: a new insight for water quality indicators. AB - Conventional procedures for qualitative assessment of coliphage are time consuming multiple step approach for achieving results. A modified and rapid technique has been introduced for determination of coliphage contamination among potable water sources during water borne outbreaks. During December 2013, 40 water samples from different potable water sources, were received for water quality analyses, from a jaundice affected Municipality of West Bengal, India. Altogether, 30% water samples were contaminated with coliform (1-20 cfu/ml) and 5% with E. coli (2-5 cfu/ml). Among post-outbreak samples, preponderance of coliform has decreased (1-4 cfu/ml) with total absence of E. coli. While standard technique has detected 55% outbreak samples with coliphage contamination, modified technique revealed that 80%, double than that of bacteriological identification rate, were contaminated with coliphages (4-20 pfu/10 ml). However, post-outbreak samples were detected with 1-5 pfu/10 ml coliphages among 20% samples. Coliphage detection rate through modified technique was nearly double (50%) than that of standard technique (27.5%). In few samples (with coliform load of 10-100 cfu/ml), while modified technique could detect coliphages among six samples (10-20 pfu/10 ml), standard protocol failed to detect coliphage in any of them. An easy, rapid and accurate modified technique has thereby been implemented for coliphage assessment from water samples. Coliform free water does not always signify pathogen free potable water and it is demonstrated that coliphage is a more reliable 'biomarker' to ascertain contamination level in potable water. PMID- 25128452 TI - Wetting of nanophases: Nanobubbles, nanodroplets and micropancakes on hydrophobic surfaces. AB - The observation by Atomic Force Microscopy of a range of nanophases on hydrophobic surfaces poses some challenging questions, not only related to the stability of these objects but also regarding their wetting properties. Spherical capped nanobubbles are observed to exhibit contact angles that far exceed the macroscopic contact angle measured for the same materials, whereas nanodroplets exhibit contact angles that are much the same as the macroscopic contact angle. Micropancakes are reported to consist of gas, in which case their wetting properties are mysterious. They should only be stable when the van der Waals forces act to thicken the film whereas for a gas, the van der Waals forces will always act to thin the film. Here we examine the available evidence and contribute some additional experiments in order to review our understanding of the wetting properties of these nanophases. We demonstrate that if in fact micropancakes consist of a contaminant their wetting properties can be explained, though the very high contact angles of nanobubbles remain unexplained. PMID- 25128453 TI - Serum levels of BDNF, folate and homocysteine: in relation to hippocampal volume and psychopathology in drug naive, first episode schizophrenia. AB - OBJECTIVE: The present study was to examine serum levels of brain-derived neurotrophic factor (BDNF), folate, homocysteine (Hcy), and their relationships with hippocampal volume and psychopathology in drug naive, first episode schizophrenia. METHOD: Drug naive, first episode schizophrenia patients and healthy controls were enrolled in the study. Serum levels of BDNF, folate and Hcy were measured using enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA), and enzymatic cycling method respectively. Hippocampus was parcellated and bilateral hippocampal volumes were measured using FreeSurfer. RESULTS: Forty-six patients with drug naive, first episode schizophrenia (SZ group) and 30 healthy controls (control group) were enrolled. The SZ group had significantly lower serum levels of BDNF and folate, and significantly higher serum levels of Hcy compared with the control group (p=0.013, p<0.001, p=0.003 respectively). There were no significant differences in hippocampal volumes between the two groups (ps>0.2). Within the SZ group, there were significant positive relationships between serum levels of BDNF and both left and right hippocampal volumes (r=0.327, p=0.026; r=0.338, p=0.022 respectively). In contrast, such relationships did not exist in the control group. Within the SZ group, there were significant negative relationships between serum levels of folate and PANSS-total scores and PANSS-negative symptom scores (r=0.319, p=0.031; r=0.321, p=0.030 respectively); and there was a positive relationship between serum levels of Hcy and PANSS-total scores (r=0.312, p=0.035). Controlling for potential confounding variables resulted in similar findings. CONCLUSIONS: Drug naive, first episode schizophrenia presents decreased serum levels of BDNF, folate and increased serum levels of Hcy, which may play an important role in the neurodevelopmental process and clinical manifestation of schizophrenia. PMID- 25128454 TI - Standard cardiovascular disease risk algorithms underestimate the risk of cardiovascular disease in schizophrenia: evidence from a national primary care database. AB - BACKGROUND: Schizophrenia is associated with increased cardiovascular mortality. Although cardiovascular disease (CVD) risk prediction algorithms are widely in the general population, their utility for patients with schizophrenia is unknown. METHODS: A primary care dataset was used to compare CVD risk scores (Joint British Societies (JBS) score), cardiovascular risk factors, rates of pre existing CVD and age of first diagnosis of CVD for schizophrenia (n=1997) relative to population controls (n=215,165). RESULTS: Pre-existing rates of CVD and the recording of risk factors for those without CVD were higher in the schizophrenia cohort in the younger age groups, for both genders. Those with schizophrenia were more likely to have a first diagnosis of CVD at a younger age, with nearly half of men with schizophrenia plus CVD diagnosed under the age of 55 (schizophrenia men 46.1% vs. control men 34.8%, p<0.001; schizophrenia women 28.9% vs. control women 23.8%, p<0.001). However, despite high rates of CVD risk factors within the schizophrenia group, only a very small percentage (3.2% of men and 7.5% of women) of those with schizophrenia under age 55 were correctly identified as high risk for CVD according to the JBS risk algorithm. CONCLUSION: The JBS2 risk score identified only a small proportion of individuals with schizophrenia under the age of 55 as being at high risk of CVD, despite high rates of risk factors and high rates of first diagnosis of CVD within this age group. The validity of CVD risk prediction algorithms for schizophrenia needs further research. PMID- 25128456 TI - Discovery of a novel HIV-1 integrase inhibitor from natural compounds through structure based virtual screening and cell imaging. AB - The interaction between HIV-1 integrase and LEDGF/P75 has been validated as a target for anti-HIV drug development. Based on the crystal structure of integrase in complex with LEDGF/P75, a library containing 80 thousand natural compounds was filtered with virtual screening. 11 hits were selected for cell based assays. One compound, 3-(1,3-benzothiazol-2-yl)-8-{[bis(2-hydroxyethyl)amino]methyl}-7 hydroxy-2H-chromen-2-one (D719) inhibited integrase nuclear translocation in cell imaging. The binding mode of D719 was analyzed with molecular simulation. The anti-HIV activity of D719 was assayed by measuring the p24 antigen production in acute infection. The structure characteristics of D719 may provide valuable information for integrase inhibitor design. PMID- 25128455 TI - Poly (ADP-ribose) polymerase inhibition enhances trastuzumab antitumour activity in HER2 overexpressing breast cancer. AB - AIM: Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in Breast Cancer (BRCA) deficient breast cancer, but not in molecularly unselected patient populations. Two lines of research in this field are needed: the identification of novel subsets of patients that could potentially benefit from PARP inhibitors and the discovery of suitable targeted therapies for combination strategies. METHODS: We tested PARP inhibition, alone or combined with the anti-HER2 antibody trastuzumab on HER2+ breast cancer. We used two PARP inhibitors in clinical development, olaparib and rucaparib, as well as genetic downmodulation of PARP-1 for in vitro studies. DNA damage was studied by the formation of gammaH2AX foci and comet assay. Finally, the in vivo anti-tumour effect of olaparib and trastuzumab was examined in nude mice subcutaneously implanted with BT474 cells. RESULTS: In a panel of four HER2 overexpressing breast cancer cell lines, both olaparib and rucaparib significantly decreased cell growth and enhanced anti-tumour effects of trastuzumab. Cells exposed to olaparib and trastuzumab had greater DNA damage than cells exposed to each agent alone. Mechanistic exploratory assays showed that trastuzumab downmodulated the homologous recombination protein proliferating cell nuclear antigen (PCNA). Combination treatment in the BT474 xenograft model resulted in enhanced growth inhibition, reduced tumour cell proliferation, and increased DNA damage and apoptosis. CONCLUSION: Taken together, our results show that PARP inhibition has antitumour effects and increases trastuzumab activity in HER2 overexpressing breast cancer. These findings make this novel combination a promising strategy for clinical development. PMID- 25128457 TI - Red chlorophyll excitation dynamics in Arthrospira platensis photosystem I trimeric complexes as studied by femtosecond transient absorption spectroscopy. AB - Femtosecond absorption spectroscopy was applied to study for the first time excitation dynamics in isolated photosystem I trimers from Arthrospira platensis, which display extremely long-wavelength absorption peaks. Pump-probe spectra observed at 77K in the timescale of dozens of picoseconds upon 70-fs excitation revealed two maxima near 710 and 730 nm, which correspond to red chlorophyll forms. Bleaching at 680 nm developed in ~ 200 fs, whereas the bleaching kinetics at 710 and 730 nm exhibited two components with time constants of 1 and 5.5 ps. Comparison of the kinetics of bleaching development at 710 nm and 730 nm with that of bleaching decay at 680 nm indicated that both long-wavelength forms of trimers are populated mainly via direct energy transfer from bulk chlorophyll. PMID- 25128458 TI - mTOR regulates the nucleoplasmic diffusion of Xrn2 under conditions of heat stress. AB - Stress induces various responses, including translational suppression and tRNA degradation in mammals. Previously, we showed that heat stress induces degradation of initiator tRNA(Met) (iMet) through 5'-3' exoribonuclease Xrn1 and Xrn2, respectively. In addition, we found that rapamycin inhibits the degradation of iMet under heat stress conditions. Here, we report that the mammalian target of rapamycin (mTOR) regulates the diffusion of Xrn2 from the nucleolus to the nucleoplasm, facilitating the degradation of iMet under conditions of heat stress. Our results suggest a mechanism of translational suppression through mTOR regulated iMet degradation in mammalian cells. PMID- 25128459 TI - MicroRNAs in the interaction between host and bacterial pathogens. AB - MicroRNAs (miRNAs) are small non-coding RNAs with a central role in the post transcriptional control of gene expression, that have been implicated in a wide range of biological processes. Regulation of miRNA expression is increasingly recognized as a crucial part of the host response to infection by bacterial pathogens, as well as a novel molecular strategy exploited by bacteria to manipulate host cell pathways. Here, we review the current knowledge of bacterial pathogens that modulate host miRNA expression, focusing on mammalian host cells, and the implications of miRNA regulation on the outcome of infection. The emerging role of commensal bacteria, as part of the gut microbiota, on host miRNA expression in the presence or absence of bacterial pathogens is also discussed. PMID- 25128460 TI - Vitamin D reduces the differentiation and expansion of Th17 cells in young asthmatic children. AB - Vitamin D [25(OH)D3] deficiency has been associated with asthma as in many inflammatory and autoimmune pathologies; however, there is still a lack of data about the effects of administration of vitamin D in immune regulation in young asthmatic patients. In this study, we investigated its inhibitory effect on the immune response in young asthmatic patients and the possible mechanisms involved. Peripheral blood CD4(+) T cells from 10 asthmatic patients and 10 healthy controls were cultured under Th17 polarizing conditions in the presence or absence of [25(OH)D3], IL-17 cytokine production was determined by ELISA and flow cytometry. Messenger RNA (mRNA) expression of several factors related to Th17 cell function was determined by real-time PCR. The effect of [25(OH)D3]-treated dendritic cells (DCs) on CD4(+) T cell response was determined by ELISA and flow cytometry. Stimulation of naive CD4(+) T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in asthmatic patients than healthy controls. The addition of [25(OH)D3] significantly inhibited Th17 cell differentiation both in patients [P<0.001] and in normal controls [P=0.001] in a dose-dependent way. [25(OH)D3] was able to inhibit the gene expression of RORC, IL-17, IL-23R, and CCR6. [25(OH)D3]-treated DCs significantly inhibited IL-17 production [P=0.002] and decreased the percentage of CD4(+)IL-17(+) [P=0.007] in young asthmatics. The findings suggest that the inhibitory effect of [25(OH)D3] on the Th17 response was mediated via both T cells and DCs. DCs pathway is involved in the direct inhibition of 25(OH)D3 on Th17 cell differentiation in young asthmatics. PMID- 25128461 TI - Measures of outdoor play and independent mobility in children and youth: A methodological review. AB - OBJECTIVES: Declines in children's outdoor play have been documented globally, which are partly due to heightened restrictions around children's independent mobility. Literature on outdoor play and children's independent mobility is increasing, yet no paper has summarized the various methodological approaches used. A methodological review could highlight most commonly used measures and comprehensive research designs that could result in more standardized methodological approaches. DESIGN: Methodological review. METHODS: A standardized protocol guided a methodological review of published research on measures of outdoor play and children's independent mobility in children and youth (0-18 years). Online searches of 8 electronic databases were conducted and studies included if they contained a subjective/objective measure of outdoor play or children's independent mobility. References of included articles were scanned to identify additional articles. RESULTS: Twenty-four studies were included on outdoor play, and twenty-three on children's independent mobility. Study designs were diverse. Common objective measures included accelerometry, global positioning systems and direct observation; questionnaires, surveys and interviews were common subjective measures. Focus groups, activity logs, monitoring sheets, travel/activity diaries, behavioral maps and guided tours were also utilized. Questionnaires were used most frequently, yet few studies used the same questionnaire. Five studies employed comprehensive, mixed-methods designs. CONCLUSIONS: Outdoor play and children's independent mobility have been measured using a wide variety of techniques, with only a few studies using similar methodologies. A standardized methodological approach does not exist. Future researchers should consider including both objective measures (accelerometry and global positioning systems) and subjective measures (questionnaires, activity logs, interviews), as more comprehensive designs will enhance understanding of each multidimensional construct. Creating a standardized methodological approach would improve study comparisons. PMID- 25128462 TI - [Incidence, management and costs of adverse effects in chronic hepatitis C patients on triple therapy with telaprevir or boceprevir: first 12 weeks of treatment]. AB - INTRODUCTION: The aim of the study was to analyze the incidence, management and cost associated to hematological and dermatological adverse effects (AE) in chronic hepatitis C patients on triple therapy (TT) with telaprevir (TVR) or boceprevir (BOC). METHODS: An analysis was made on the data recorded on patients who started treatment with TVR or BOC associated with peginterferon alfa and ribavirin in a 12-week follow-up period. RESULTS: Fifty-three patients were included (TVR n=36; BOC n=17). Thrombocytopenia (83% TVR vs. 88% BOC) followed by neutropenia (89% TVR vs. 82% BOC) were the most common AE. Dermatological AE were observed in 32% of patients. Eleven patients required treatment discontinuation (all of them received TVR), and toxicity was the main reason for discontinuation (64%). The percentage of patients who required supportive treatment for management of AE was 66%. The most used supportive treatment was erythropoietin. Eight patients required emergency health care, and 2 were hospitalized due to AE. Total cost of additional supportive resources was 32,522? (625 [SD=876]?/patient) (TVR 759 [SD=1,022]?/patient vs. BOC 349 [SD=327]?/patient; P>.05). Patients with gradeiii-iv toxicity required greater supportive care with higher costs, compared to patients with gradei-ii toxicity (849 [SD=1,143]?/patient vs. 387 [SD=397]?/patient; P=.053). CONCLUSION: The addition of new protease inhibitors to conventional treatment leads to a higher incidence of hematological AE in our study, compared to data described in clinical trials. The elevated incidence of AE involves the use of supportive care, increasing total costs of therapy. PMID- 25128463 TI - Cocaine- and amphetamine-regulated transcript peptide increases mitochondrial respiratory chain complex II activity and protects against oxygen-glucose deprivation in neurons. AB - The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART55-102, increased the survival rate, but decreased the mortality of neurons exposed to oxygen-glucose deprivation (OGD), in a dose-dependent manner. The above-mentioned effects of CART55-102 were most significant at 0.4nM. These results indicated that CART55-102 suppressed neurotoxicity and enhanced neuronal survival after oxygen-glucose deprivation. CART55-102 (0.4nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In summary, CART55-102 suppressed oxidative stress in oxygen-glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART55-102 as an antioxidant drug. PMID- 25128465 TI - Function of duck RIG-I in induction of antiviral response against IBDV and avian influenza virus on chicken cells. AB - The avian influenza (AI) H9N2 virus and IBDV are two major problems in the poultry industry. They have been prevalent among domestic poultry in Asia for many years and have caused considerable economic losses. Retinoic-acid-induced gene I (RIG-I) is a cytoplasmic sensor of dsRNA and ssRNA. It can detect Encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV) in human cells, influenza virus in duck leads to production of IFN-beta and IFN-stimulated antiviral genes and reductions in the replication of RNA virus. Chickens, which lack RIG-I, are more sensitive to influenza virus than ducks. However, little is known about the roles of duck RIG-I (dRIG-I) in the detection of IBDV and AI H9N2 in chicken cells DF-1. The purpose of this study was to examine the function of dRIG-I in the recognition of IBDV Ts strain and H9N2 A/Chicken/Shandong/ZB/2007(ZB07) and in the induction of antiviral gene expression to gain an understanding of antiviral ability of dRIG-I in chicken cells against dsRNA virus IBDV and ssRNA virus ZB07. After challenge with the IBDV Ts strain and ZB07 the expression levels of Type I IFN (IFN-beta and IFN alpha) and IFN-induced antiviral genes (Mx and PKR) were significantly up regulated in dRIG-I-transfected DF-1cells compared with the empty-vector transfected control. dRIG-I knockdown experiments further proved that dRIG-I is essential to sensing IBDV and ZB07 in duck embryo fibroblasts (DEF). Growth curves showed that dRIG-I repressed the replication of IBDV and almost blunted the growth of ZB07 in DF-1. Apoptosis analysis revealed that dRIG-I increase the number of the survival cells after IBDV Ts strain or ZB07 infection relative to the empty-vector-transfected control. These results indicate that dRIG-I can up regulates type I IFN and reduce viral gene expression and viral replication and protect chicken cells from virus-induced apoptosis during ZB07 and IBDV infection. PMID- 25128466 TI - Egress of budded virions of Autographa californica nucleopolyhedrovirus does not require activity of Spodoptera frugiperda HSP/HSC70 chaperones. AB - The induction of heat shock proteins in baculovirus infected cells is well documented. However a role of these chaperones in infection cycle remains unknown. The observation that HSP70s are associated with virions of different baculoviruses reported by several researchers suggests that HSPs might be structural components of viruses or involved in virion assembly. These hypotheses were examined by using a novel inhibitor of the ATPase and chaperoning activity of HSP/HSC70s, VER-155008. When VER-155008 was added early in infection, the synthesis of viral proteins, genome replication and the production of budded virions (BV) were markedly inhibited indicating the dependence of virus reproduction on host chaperones. However, BV production was unaffected when VER 155008 was added in the mid-replication phase which is after accumulation of products required for completion of the viral DNA replication. These results suggest that the final stages in assembly of BV and their egress from cells do not depend on chaperone activity of host HSP/HSC70s. PMID- 25128464 TI - Functional connectivity of dorsal and ventral frontoparietal seed regions during auditory orienting. AB - Our ability to refocus auditory attention is vital for even the most routine day to-day activities. Shifts in auditory attention can be initiated "voluntarily," or triggered "involuntarily" by unexpected novel sound events. Here we employed psychophysiological interaction (PPI) analyses of auditory functional MRI data, to compare functional connectivity patterns of distinct frontoparietal cortex regions during cued voluntary vs. novelty-driven involuntary auditory attention shifting. Overall, our frontoparietal seed regions exhibited significant PPI increases with auditory cortex (AC) areas during both cued and novelty-driven orienting. However, significant positive PPI patterns associated with voluntary auditory attention (cue>novel task regressor), but mostly absent in analyses emphasizing involuntary orienting (novel>cue task regressor), were observed with seeds within the frontal eye fields (FEF), superior parietal lobule (SPL), and right supramarginal gyri (SMG). In contrast, significant positive PPIs associated selectively with involuntary orienting were observed between ACs and seeds within the bilateral anterior interior frontal gyri (IFG), left posterior IFG, SMG, and posterior cingulate cortices (PCC). We also found indices of lateralization of different attention networks: PPI increases selective to voluntary attention occurred primarily within right-hemispheric regions, whereas those related to involuntary orienting were more frequent with left-hemisphere seeds. In conclusion, despite certain similarities in PPI patterns across conditions, the more dorsal aspects of right frontoparietal cortex demonstrated wider connectivity during cued/voluntary attention shifting, whereas certain left ventral frontoparietal seeds were more widely connected during novelty triggered/involuntary orienting. Our findings provide partial support for distinct attention networks for voluntary and involuntary auditory attention. PMID- 25128467 TI - FoxO proteins' nuclear retention and BH3-only protein Bim induction evoke mitochondrial dysfunction-mediated apoptosis in berberine-treated HepG2 cells. AB - Mammalian forkhead-box family members belonging to the 'O' category (FoxO) manipulate a plethora of genes modulating a wide array of cellular functions including cell cycle regulation, apoptosis, DNA damage repair, and energy metabolism. FoxO overexpression and nuclear accumulation have been reported to show correlation with hindered tumor growth in vitro and size in vivo, while FoxO's downregulation via phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway has been linked with tumor promotion. In this study, we have explored for the first time intervention of berberine, a plant-derived isoquinoline alkaloid, with FoxO family proteins in hepatoma cells. We observed that berberine significantly upregulated the mRNA expression of both FoxO1 and FoxO3a. Their phosphorylation-mediated cytoplasmic sequestration followed by degradation was prevented by berberine-induced downmodulation of the PI3K/Akt/mTOR pathway which promoted FoxO nuclear retention. PTEN, a tumor suppressor gene and negative regulator of the PI3K/Akt axis, was upregulated while phosphorylation of its Ser380 residue (possible mechanism of PTEN degradation) was significantly decreased in treated HepG2 cells. Exposure to berberine induced a significant increase in transcriptional activity of FoxO, as shown by GFP reporter assay. FoxO transcription factors effectively heightened BH3-only protein Bim expression, which in turn, being a direct activator of proapoptotic protein Bax, altered Bax/Bcl-2 ratio, culminating into mitochondrial dysfunction, caspases activation, and DNA fragmentation. The pivotal role of Bim in berberine-mediated cytotoxicity was further corroborated by knockdown experiments where Bim-silencing partially restored HepG2 cell viability during berberine exposure. In addition, a correlation between oxidative overload and FoxO's nuclear accumulation via JNK activation was evident as berberine treatment led to a pronounced increase in JNK phosphorylation together with enhanced ROS generation, lipid peroxidation, decreased activities of superoxide dismutase and catalase, and diminished glutathione levels. Thus, our findings suggest that the antiproliferative effect of berberine may in part be due to mitochondria-mediated apoptosis with Bim acting as a pivotal downstream factor of FoxO-induced transcriptional activation. PMID- 25128468 TI - Quality care outcomes following transitional care interventions for older people from hospital to home: a systematic review. AB - BACKGROUND: Provision of high quality transitional care is a challenge for health care providers in many western countries. This systematic review was conducted to (1) identify and synthesise research, using randomised control trial designs, on the quality of transitional care interventions compared with standard hospital discharge for older people with chronic illnesses, and (2) make recommendations for research and practice. METHODS: Eight databases were searched; CINAHL, Psychinfo, Medline, Proquest, Academic Search Complete, Masterfile Premier, SocIndex, Humanities and Social Sciences Collection, in addition to the Cochrane Collaboration, Joanna Briggs Institute and Google Scholar. Results were screened to identify peer reviewed journal articles reporting analysis of quality indicator outcomes in relation to a transitional care intervention involving discharge care in hospital and follow-up support in the home. Studies were limited to those published between January 1990 and May 2013. Study participants included people 60 years of age or older living in their own homes who were undergoing care transitions from hospital to home. Data relating to study characteristics and research findings were extracted from the included articles. Two reviewers independently assessed studies for risk of bias. RESULTS: Twelve articles met the inclusion criteria. Transitional care interventions reported in most studies reduced re-hospitalizations, with the exception of general practitioner and primary care nurse models. All 12 studies included outcome measures of re-hospitalization and length of stay indicating a quality focus on effectiveness, efficiency, and safety/risk. Patient satisfaction was assessed in six of the 12 studies and was mostly found to be high. Other outcomes reflecting person and family centred care were limited including those pertaining to the patient and carer experience, carer burden and support, and emotional support for older people and their carers. Limited outcome measures were reported reflecting timeliness, equity, efficiencies for community providers, and symptom management. CONCLUSIONS: Gaps in the evidence base were apparent in the quality domains of timeliness, equity, efficiencies for community providers, effectiveness/symptom management, and domains of person and family centred care. Further research that involves the person and their family/caregiver in transitional care interventions is needed. PMID- 25128469 TI - Love-Hate ligands for high resolution analysis of strain in ultra-stable protein/small molecule interaction. AB - The pathway of ligand dissociation and how binding sites respond to force are not well understood for any macromolecule. Force effects on biological receptors have been studied through simulation or force spectroscopy, but not by high resolution structural experiments. To investigate this challenge, we took advantage of the extreme stability of the streptavidin-biotin interaction, a paradigm for understanding non-covalent binding as well as a ubiquitous research tool. We synthesized a series of biotin-conjugates having an unchanged strong-binding biotin moiety, along with pincer-like arms designed to clash with the protein surface: 'Love-Hate ligands'. The Love-Hate ligands contained various 2,6-di ortho aryl groups, installed using Suzuki coupling as the last synthetic step, making the steric repulsion highly modular. We determined binding affinity, as well as solving 1.1-1.6A resolution crystal structures of streptavidin bound to Love-Hate ligands. Striking distortion of streptavidin's binding contacts was found for these complexes. Hydrogen bonds to biotin's ureido and thiophene rings were preserved for all the ligands, but biotin's valeryl tail was distorted from the classic conformation. Streptavidin's L3/4 loop, normally forming multiple energetically-important hydrogen bonds to biotin, was forced away by clashes with Love-Hate ligands, but Ser45 from L3/4 could adapt to hydrogen-bond to a different part of the ligand. This approach of preparing conflicted ligands represents a direct way to visualize strained biological interactions and test protein plasticity. PMID- 25128470 TI - Intranasal nerve growth factor attenuates tau phosphorylation in brain after traumatic brain injury in rats. AB - Traumatic brain injury (TBI) is a considerable cause of mild cognitive impairment and dementia. Intranasal administration of nerve growth factor (NGF) has previously been found to improve cognitive function after TBI, but the mechanism remains unclear. This study aimed to investigate the effects of intranasal NGF on the tau hyperphosphorylation following TBI. A modified Feeney's weight-drop model was used to induce TBI. Rats were randomly divided into control group, TBI group, TBI+NGF group, TBI+PDTC group and TBI+IL-1ra group. Rats in TBI+NGF group were administered with NGF (5 MUg/d) for 3d before surgery. Hyperphosphorylated tau protein was remarkable in the peri-contusional cortex area with TBI. Both western blotting and immunostaining results displayed intranasal pretreatment of NGF significantly reduced tau phosphorylation. To evaluate the underlying mechanism, the levels of glycogen synthase kinase 3beta (GSK-3beta), interleukin-1beta (IL 1beta), and the DNA binding activity of nuclear factor-kappaB (NF-kappaB) were assayed. NGF markedly inhibited GSK-3beta. NGF also reduced TBI-induced elevation of IL-1beta and NF-kappaB DNA binding activity. Furthermore, PDTC and IL-1ra were injected to prove a potential signaling pathway among NF-kappaB, IL-1beta and GSK 3beta. Taken together, these findings demonstrated that intranasal NGF could effectively attenuate the hyperphosphorylation of tau after TBI, which might involve an integrated signaling pathway related to NF-kappaB. PMID- 25128471 TI - Familial acute necrotizing encephalopathy due to mutation in the RANBP2 gene. AB - BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare and severe parainfectious central nervous system disease in which previously healthy children develop rapidly progressive coma following viral illness. While most ANE are sporadic, familial autosomal dominant ANE due to mutations in the RANBP2 gene has been recently reported (ANE1 or infection-induced acute encephalopathy-3 (IIAE3)). To date, only few IIAE3 families with ADANE episodes have been described. OBJECTIVE: To report a new family with ADANE, describe clinical and radiological features and discuss differential diagnosis including Leigh syndrome or multiple sclerosis. OBSERVATION: The family included 3 symptomatic individuals and one 59 year-old asymptomatic obligate carrier. Patients presented acute episodes of encephalopathy few days after common viral infection. Ages of onset ranged from 6 months to 5 years. Episodes not only occurred in childhood but also recurred in adulthood. Initial neurological signs included coma, focal neurological deficits and seizures. MRI showed typical necrotizing lesions primarily in the thalamus and brainstem, and in the temporal lobes and insula. CSF cell count and cultures were normal during episodes. RANBP2 gene screening identified pathogenic heterozygous c.1754C>T mutation (p.Thr585Met). Episodes led to cognitive or physical handicap in 2 patients and were fatal in one child. CONCLUSION: IIAE3 or ADANE due to RANBP2 mutations has a large clinical heterogeneity. Our family illustrates the associated phenotypes from asymptomatic carrier to severe episodes of encephalopathy. Based on MRI features, the genetic IIAE3 diagnosis is important since prophylaxis and symptomatic management of infections may be beneficial, possibly in association with steroid or gammaglobulins. PMID- 25128472 TI - Muscle and nerve inflammation in intensive care unit-acquired weakness: a systematic translational review. AB - BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is an important complication of critical illness. The main risk factors, sepsis and the systemic inflammatory response syndrome, suggest an inflammatory pathogenesis. In this systematic translational review we summarize current knowledge on inflammation in muscle and nerve tissue in animal models of ICU-AW and in critically ill patients with ICU-AW. METHODS: We conducted a systematic search in the databases of MEDLINE, EMBASE and Web of Science using predefined search and selection criteria. From the included studies we extracted data on study characteristics and on inflammation in muscle and nerve tissue. RESULTS: The literature search yielded 349 unique articles, of which 12 animal studies and 20 human studies fulfilled the in- and exclusion criteria. All studies had important shortcomings in methodological quality. In the animal studies, inflammation of muscle tissue was found, represented by cellular infiltration and increased local levels of various inflammatory mediators. In human studies, high levels of various inflammatory mediators were found in muscle and nerve tissue of ICU-AW patients. CONCLUSION: This systematic translational review suggests a role for local inflammation in ICU-AW, but the available evidence is limited and studies have severe methodological limitations. PMID- 25128474 TI - Lack of angiopoietin-like-2 expression limits the metabolic stress induced by a high-fat diet and maintains endothelial function in mice. AB - BACKGROUND: Angiopoietin-like-2 (angptl2) is produced by several cell types including endothelial cells, adipocytes and macrophages, and contributes to the inflammatory process in cardiovascular diseases. We hypothesized that angptl2 impairs endothelial function, and that lowering angptl2 levels protects the endothelium against high-fat diet (HFD)-induced fat accumulation and hypercholesterolemia. METHODS AND RESULTS: Acute recombinant angptl2 reduced (P<0.05) acetylcholine-mediated vasodilation of isolated wild-type (WT) mouse femoral artery, an effect reversed (P<0.05) by the antioxidant N-acetylcysteine. Accordingly, in angptl2 knockdown (KD) mice, ACh-mediated endothelium-dependent vasodilation was greater (P<0.05) than in WT mice. In arteries from KD mice, prostacyclin contributed to the overall dilation unlike in WT mice. After a 3 month HFD, overall vasodilation was not altered, but dissecting out the endothelial intrinsic pathways revealed that NO production was reduced in arteries isolated from HFD-fed WT mice (P<0.05), while NO release was maintained in KD mice. Similarly, endothelium-derived hyperpolarizing factor (EDHF) was preserved in mesenteric arteries from HFD-fed KD mice but not in those from WT mice. Finally, the HFD increased (P<0.05) total cholesterol-to-high-density lipoprotein ratios, low-density lipoprotein-to-high-density lipoprotein ratios, and leptin levels in WT mice only, while glycemia remained similar in the 2 strains. KD mice displayed less triglyceride accumulation in the liver (P<0.05 versus WT), and adipocyte diameters in mesenteric and epididymal white adipose tissues were smaller (P<0.05) in KD than in WT fed an HFD, while inflammatory gene expression increased (P<0.05) in the fat of WT mice only. CONCLUSIONS: Lack of angptl2 expression limits the metabolic stress induced by an HFD and maintains endothelial function in mice. PMID- 25128476 TI - The impact of previous hospitalization in the preceding 90 days on the outcome in critically ill patients with gram-negative bloodstream infection. AB - We conducted a retrospective cohort study to evaluate the impact of previous hospitalization in the preceding 90 days on mortality in critically ill patients with gram-negative bloodstream infection (BSI) and to identify the risk factors for 30-day mortality in these patients. Of 89 critically ill patients with gram negative BSI, 42 patients had previous hospitalization in the preceding 90 days. Multivariate Cox regression analysis revealed previous hospitalization in the preceding 90 days as a significant predictor for 30-day mortality (hazard ratio [HR], 2.10; 95% confidence interval [CI], 1.11-3.94; P = 0.022), along with Acute Physiology and Chronic Health Evaluation II score at BSI onset (HR, 1.08; 95% CI, 1.04-1.12; P < 0.001), liver cirrhosis (HR, 3.61; 95% CI, 1.46-8.94; P = 0.006), and inappropriate definitive antimicrobial therapy (HR, 4.28; 95% CI, 2.17-8.45; P < 0.001). The effect of previous hospitalization in the preceding 90 days should be considered in evaluating the risk for 30-day mortality when treating such patients, and further study is required. PMID- 25128475 TI - Transcriptomic analysis of Clostridium thermocellum Populus hydrolysate-tolerant mutant strain shows increased cellular efficiency in response to Populus hydrolysate compared to the wild type strain. AB - BACKGROUND: The thermophilic, anaerobic bacterium, Clostridium thermocellum is a model organism for consolidated processing due to its efficient fermentation of cellulose. Constituents of dilute acid pretreatment hydrolysate are known to inhibit C. thermocellum and other microorganisms. To evaluate the biological impact of this type of hydrolysate, a transcriptomic analysis of growth in hydrolysate-containing medium was conducted on 17.5% v/v Populus hydrolysate tolerant mutant (PM) and wild type (WT) strains of C. thermocellum. RESULTS: In two levels of Populus hydrolysate medium (0% and 10% v/v), the PM showed both gene specific increases and decreases of gene expression compared to the wild type strain. The PM had increased expression of genes in energy production and conversion, and amino acid transport and metabolism in both standard and 10% v/v Populus hydrolysate media. In particular, expression of the histidine metabolism increased up to 100 fold. In contrast, the PM decreased gene expression in cell division and sporulation (standard medium only), cell defense mechanisms, cell envelope, cell motility, and cellulosome in both media. The PM downregulated inorganic ion transport and metabolism in standard medium but upregulated it in the hydrolysate media when compared to the WT. The WT differentially expressed 1072 genes in response to the hydrolysate medium which included increased transcription of cell defense mechanisms, cell motility, and cellulosome, and decreased expression in cell envelope, amino acid transport and metabolism, inorganic ion transport and metabolism, and lipid metabolism, while the PM only differentially expressed 92 genes. The PM tolerates up to 17.5% v/v Populus hydrolysate and growth in it elicited 489 genes with differential expression, which included increased expression in energy production and conversion, cellulosome production, and inorganic ion transport and metabolism and decreased expression in transcription and cell defense mechanisms. CONCLUSION: These results suggest the mechanisms of tolerance for the Populus hydrolysate-tolerant mutant strain of C. thermocellum are based on increased cellular efficiency caused apparently by downregulation of non-critical genes and increasing the expression of genes in energy production and conversion rather than tolerance to specific hydrolysate components. The wild type, conversely, responds to hydrolysate media by down-regulating growth genes and up-regulating stress response genes. PMID- 25128477 TI - Ceftazidime-avibactam and comparator agents tested against urinary tract isolates from a global surveillance program (2011). AB - Ceftazidime-avibactam, a combination of ceftazidime and the non-beta-lactam beta lactamase inhibitor avibactam, is in advanced clinical development. In this study, we report results of in vitro testing of ceftazidime-avibactam and comparator agents against a collection of urinary tract infection (UTI) isolates from the United States (USA), Europe and Mediterranean region (EMR), Latin America (LATAM), and the Asia-Pacific/South Africa regions (APAC). Clinical isolates (1 per patient episode) were collected from patients with a UTI during 2011. A total of 1797 isolates were collected from 159 medical centers. Isolates were processed at the medical centers and forwarded to a central monitoring laboratory for confirmatory identification and reference susceptibility testing. Ceftazidime-avibactam was highly active against Enterobacteriaceae and Pseudomonas aeruginosa. The MIC90 values for ceftazidime-avibactam against Enterobacteriaceae in the USA, EMR, and LATAM regions ranged from 0.25 to 0.5MUg/mL. The MIC90 in the APAC was slightly elevated at 1MUg/mL. A total of 6.1% (8/131) of Escherichia coli in the USA, 23.5% (43/183) in the EMR, 61.2% (30/49) in LATAM, and 75.0% (9/12) in APAC exhibited an extended-spectrum beta lactamase (ESBL) screen-positive phenotype. A total of 1.6% (2/129) of Klebsiella pneumoniae isolates in the USA were meropenem-non-susceptible (MIC >=2MUg/mL), but a rate of 10.3% (10/97) was observed in the EMR. All ESBL screen-positive phenotype and meropenem-non-susceptible E. coli and K. pneumoniae isolates exhibited a ceftazidime-avibactam MIC <=4MUg/mL. All isolates of P. aeruginosa in the USA and 80.9% (38/47) in the EMR were inhibited at a ceftazidime-avibactam MIC of <=8MUg/mL compared to 88.2% (15/17) and 61.7% (29/47) for ceftazidime alone. Ceftazidime-avibactam demonstrated wide in vitro activity against Gram negative bacteria from patients with UTI including high potencies against multidrug-resistant organisms. PMID- 25128478 TI - Genome wide CNV analysis reveals additional variants associated with milk production traits in Holsteins. AB - BACKGROUND: Milk production is an economically important sector of global agriculture. Much attention has been paid to the identification of quantitative trait loci (QTL) associated with milk, fat, and protein yield and the genetic and molecular mechanisms underlying them. Copy number variation (CNV) is an emerging class of variants which may be associated with complex traits. RESULTS: In this study, we performed a genome-wide association between CNVs and milk production traits in 26,362 Holstein bulls and cows. A total of 99 candidate CNVs were identified using Illumina BovineSNP50 array data, and association tests for each production trait were performed using a linear regression analysis with PCA correlation. A total of 34 CNVs on 22 chromosomes were significantly associated with at least one milk production trait after false discovery rate (FDR) correction. Some of those CNVs were located within or near known QTL for milk production traits. We further investigated the relationship between associated CNVs with neighboring SNPs. For all 82 combinations of traits and CNVs (less than 400 kb in length), we found 17 cases where CNVs directly overlapped with tag SNPs and 40 cases where CNVs were adjacent to tag SNPs. In 5 cases, CNVs located were in strong linkage disequilibrium with tag SNPs, either within or adjacent to the same haplotype block. There were an additional 20 cases where CNVs did not have a significant association with SNPs, suggesting that the effects of those CNVs were probably not captured by tag SNPs. CONCLUSION: We conclude that combining CNV with SNP analyses reveals more genetic variations underlying milk production traits than those revealed by SNPs alone. PMID- 25128479 TI - Opportunities and challenges in implementing community based skilled birth attendance strategy in Kenya. AB - BACKGROUND: Availability of skilled care at birth remains a major problem in most developing countries. In an effort to increase access to skilled birth attendance, the Kenyan government implemented the community midwifery programme in 2005. The aim of this programme was to increase women's access to skilled care during pregnancy, childbirth and post-partum within their communities. METHODS: Qualitative research involving in-depth interviews with 20 community midwives and six key informants. The key informants were funder, managers, coordinators and supervisors of the programme. Interviews were conducted between June to July, 2011 in two districts in Western and Central provinces of Kenya. RESULTS: Findings showed major challenges and opportunities in implementing the community midwifery programme. Challenges of the programme were: socio-economic issues, unavailability of logistics, problems of transportation for referrals and insecurity. Participants also identified the advantages of having midwives in the community which were provision of individualised care; living in the same community with clients which made community midwives easily accessible; and flexible payment options. CONCLUSIONS: Although the community midwifery model is a culturally acceptable method to increase skilled birth attendance in Kenya, the use of skilled birth attendance however remains disproportionately lower among poor mothers. Despite several governmental efforts to increase access and coverage of delivery services to the poor, it is clear that the poor may still not access skilled care even with skilled birth attendants residing in the community due to several socio-economic barriers. PMID- 25128480 TI - Spatiotemporal analysis of sandfly fauna (Diptera: Psychodidae) in an endemic area of visceral leishmaniasis at Pantanal, central South America. AB - BACKGROUND: Environmental changes caused by urbanization can cause alterations in the ecology and behavior of sandflies and in the epidemiology of leishmaniasis. Geotechnological tools allow the analysis and recognition of spatiotemporal patterns by monitoring and mapping risk areas of this vector-borne disease. This study aims to describe the sandfly fauna in the municipality of Corumba and to compare it with the data described in a three-year period from 1984 to 1986 by Galati. A further aim was to analyze the influence of environmental changes on the composition of the fauna. METHODS: Captures were conducted weekly from April 2012 to March 2013, in intra and peridomicile areas with automatic light traps, from 6:00 pm to 6:00 am. The following indices were calculated for both periods analyzed: Standardized Index of Species Abundance (SISA), Shannon's diversity index (H) and Pielou's index (J). The Normalized Difference Vegetation Index (NDVI) was extracted from a remote sensing LANDSAT-5 image. RESULTS: In total, 7,370 specimens (6,169 males and 1,201 females) were collected, distributed among 12 species. Lutzomyia cruzi was the most frequent species (93,79%) and the first in the ranking of standardized species abundance index in both studies. The dominance of the species Lu. cruzi in the neighborhoods of Maria Leite and Centro was demonstrated by the low equitability index. The neighborhood of Cristo Redentor had the greatest diversity of sandflies in the present study and the second greatest in the study performed by Galati et al. (Rev Saude Publica 31:378 390, 1997). Analyzing the satellite images and the NDVI from 1984 and 2010, the largest amount of dense vegetation was found in the neighborhood of Cristo Redentor. CONCLUSIONS: It was, therefore, possible to show how changes caused due to urbanization have affected the density and distribution of Lu. cruzi and other species over time. Moreover, the data suggest that different populations of sandflies adapt in different ways according to environmental conditions and the adaptation does not necessarily depends on the presence of high vegetation cover. PMID- 25128481 TI - Sleep and body mass index in adolescence: results from a large population-based study of Norwegian adolescents aged 16 to 19 years. AB - BACKGROUND: The aim of this study was to examine the association between body mass index (BMI) and sleep duration, insomnia and symptoms of obstructive sleep apnea (OSA) in adolescents. METHODS: Data were taken from a large population based study of 9,875 Norwegian adolescents aged 16-19. BMI was calculated from the self-reported body weight and categorized according to recommended age and gender specific cut offs for underweight, overweight and obesity. Detailed sleep parameters (sleep duration, insomnia, and OSA symptoms) were reported separately for weekdays and weekends. Data were analyzed using Pearson's chi-squared test and ANOVAs for simple categorical and continuous comparisons, and multinomial logistic regressions for analyses adjusting for known confounders. RESULTS: There was evidence for a curvilinear relationship between BMI and both sleep duration and insomnia for girls, whereas the relationship was linear for boys. Compared to the average weekday sleep duration among adolescents in the normal weight range (6 hrs 29 min), both underweight (5 hrs 48 min), overweight (6 hrs 13 min) and obese (5 hrs 57 min) adolescents had shorter sleep duration. OSA symptoms were linearly associated with BMI. Controlling for demographical factors as well as physical activity did not attenuate the associations. Additional adjustment for depression reduced the association between insomnia and obesity to a non significant level. The evidence for a link between both underweight and overweight/obesity, and short sleep duration and OSA symptoms remained in the fully adjusted analyses. The associations were generally stronger for girls. CONCLUSIONS: This is one of the first population-based studies to investigate the relationship between sleep and BMI in adolescents while simultaneously controlling for important confounding factors. These findings require further research to investigate the temporal association between weights and sleep problems. PMID- 25128482 TI - The effect of CTLA-4 A49G polymorphism on rheumatoid arthritis risk: a meta analysis. AB - BACKGROUND: Recently, a number of studies have been performed to explore the association between CTLA-4 A49G polymorphism and rheumatoid arthritis (RA). However, the results of previous works are still controversial and ambiguous. METHODS: In this work, we attempted to perform an updated meta-analysis of available case-control study in order to assess the association between CTLA-4 A49G polymorphism and RA risk. We searched the various citation databases without limits on languages. Article searching was performed by screening the references of retrieved studies manually. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of the association. RESULTS: We totally compiled 27 studies in 24 articles (9805 RA patients and 10691 control subjects) into our meta-analysis work. We found significant association between CTL-A4 A49G polymorphism and RA risk (GG vs. AA: OR = 1.13, 95% CI = 1.03-1.23; GA vs. AA: OR = 1.19, 95% CI = 1.07-1.33; GA + GG vs. AA: OR = 1.18, 95% CI = 1.07-1.29). In the subgroup analysis by ethnicity, evidences of significantly increased risk was also found in both Asian (GG vs. AA: OR = 1.34, 95% CI = 1.15 1.55; GA + GG vs. AA: OR = 1.24, 95% CI = 1.08-1.41) and Caucasian population (GA vs. AA: OR = 1.19, 95% CI = 1.03-1.37; GA + GG vs. AA: OR = 1.14, 95% CI = 1.01 1.29). No evidence of publication bias was found in this work. CONCLUSIONS: Our meta-analysis suggests that CTLA-4 A49G polymorphism was associated with RA risk. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_157. PMID- 25128484 TI - Overweight and obesity are linked to 10 common cancers and more than 12,000 UK cases. PMID- 25128483 TI - miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human lung adenocarcinoma cells. AB - BACKGROUND: MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood. METHODS: We detected miR-27a expression in two lung adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects of miR-27a on the metastasis and the chemosensitivity of cancer cells, using both gain- and loss-of-function studies. The correlation between miR-27a level and chemoresistance was further investigated in clinical lung adenocarcinoma specimens. RESULTS: miR-27a was significantly up-regulated in cisplatin-resistant lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-27a regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo. Further studies identified Raf Kinase Inhibitory Protein (RKIP) as a direct and functional target of miR-27a. Small interfering RNA-mediated RKIP knockdown revealed similar effects as that of ectopic miR-27a expression, while overexpression of RKIP attenuated the function of miR-27a in lung adenocarcinoma cells. Increased miR-27a expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and was proved to be correlated with low expression of RKIP, decreased sensitivity to cisplatin, and poor prognosis. CONCLUSION: Our results suggest that up-regulation of miR-27a could suppress RKIP expression and in turn contribute to chemoresistance of lung adenocarcinoma cells to cisplatin. PMID- 25128485 TI - Unfractionated heparin and placental pathology in high-risk pregnancies: secondary analysis of a pilot randomized controlled trial. AB - INTRODUCTION: Heparin is often prescribed during pregnancy with the intention of improving perinatal outcomes on the basis that it exerts an anticoagulant action in the inter-villous space. Accumulating in-vitro and in-vivo evidence indicates that heparin's beneficial effects in pregnancy may result from 'non anticoagulant' effects including the promotion of angiogenesis. METHODS: To study the effect of heparin within the placenta, we performed secondary analyses on a pilot trial where 32 women with negative thrombophilia screens and second trimester evidence of placental insufficiency were randomized to standard care or antenatal self-administration of unfractionated heparin (UFH) 7500 IU twice daily. Serial placental ultrasound images were reviewed and compared with histo pathologic findings following delivery. RESULTS: There were no differences between the two arms in either the evolution of abnormal placental lesions on ultrasound (p = 0.75) or evidence of maternal vascular under-perfusion on histopathology (p = 0.89). In pregnancies considered at increased risk for adverse pregnancy outcomes based on previous history or abnormal serum marker screen, early (second-trimester) placental ultrasound, reflecting developmental pathology had better test characteristics (sensitivity 77.8%; positive predictive value 80.8%) for predicting adverse pregnancy outcomes than third-trimester ultrasound that is reflective of placental thrombotic injury. CONCLUSIONS: Administration of UFH did not prevent the development or evolution of abnormal placental lesions on placental ultrasound or evidence of maternal vascular underperfusion on placental histo-pathology. Second-trimester placental ultrasound may be of value in predicting those at greatest risk of adverse outcomes. PMID- 25128486 TI - Report of the independent panel considering the retraction of two articles in The BMJ. PMID- 25128487 TI - UK government may face legal challenge from Philip Morris over plain cigarette packaging. PMID- 25128488 TI - The fight is on: military metaphors for cancer may harm patients. PMID- 25128493 TI - How substrate specificity is imposed on a histone demethylase--lessons from KDM2A. AB - Histone lysine methylation and demethylation regulate histone methylation dynamics, which impacts chromatin structure and function. To read and erase the methylated histone residues, lysine demethylases must specifically recognize the histone sequences and methylated sites and discriminate the degree of these methylations. In this issue of Genes & Development, Cheng and colleagues (pp. 1758-1771) determine a crystal structure of histone lysine demethylase KDM2A that specifically targets lower degrees of H3K36 methylation. The results reveal the structural basis for H3K36 substrate specificity and suggest mechanisms of Lys36 demethylation. This KDM2A-H3K36 complex structure, coupled with functional studies, provides needed insight into the process and regulation of histone demethylation. PMID- 25128495 TI - Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon. AB - To develop stem cell therapy for small intestinal (SI) diseases, it is essential to determine whether SI stem cells in culture retain their tissue regeneration capabilities. By using a heterotopic transplantation approach, we show that cultured murine SI epithelial organoids are able to reconstitute self-renewing epithelia in the colon. When stably integrated, the SI-derived grafts show many features unique only to the SI but distinct from the colonic epithelium. Our study provides evidence that cultured adult SI stem cells could be a source for cell therapy of intestinal diseases, maintaining their identity along the gastrointestinal tract through an epithelium-intrinsic mechanism. PMID- 25128494 TI - Limiting the power of p53 through the ubiquitin proteasome pathway. AB - The ubiquitin proteasome pathway is critical in restraining the activities of the p53 tumor suppressor. Numerous E3 and E4 ligases regulate p53 levels. Additionally, deubquitinating enzymes that modify p53 directly or indirectly also impact p53 function. When alterations of these proteins result in increased p53 activity, cells arrest in the cell cycle, senesce, or apoptose. On the other hand, alterations that result in decreased p53 levels yield tumor-prone phenotypes. This review focuses on the physiological relevance of these important regulators of p53 and their therapeutic implications. PMID- 25128496 TI - A molecular threading mechanism underlies Jumonji lysine demethylase KDM2A regulation of methylated H3K36. AB - The dynamic reversible methylation of lysine residues on histone proteins is central to chromatin biology. Key components are demethylase enzymes, which remove methyl moieties from lysine residues. KDM2A, a member of the Jumonji C domain-containing histone lysine demethylase family, specifically targets lower methylation states of H3K36. Here, structural studies reveal that H3K36 specificity for KDM2A is mediated by the U-shaped threading of the H3K36 peptide through a catalytic groove within KDM2A. The side chain of methylated K36 inserts into the catalytic pocket occupied by Ni(2+) and cofactor, where it is positioned and oriented for demethylation. Key residues contributing to K36me specificity on histone H3 are G33 and G34 (positioned within a narrow channel), P38 (a turn residue), and Y41 (inserts into its own pocket). Given that KDM2A was found to also bind the H3K36me3 peptide, we postulate that steric constraints could prevent alpha-ketoglutarate from undergoing an "off-line"-to-"in-line" transition necessary for the demethylation reaction. Furthermore, structure-guided substitutions of residues in the KDM2A catalytic pocket abrogate KDM2A-mediated functions important for suppression of cancer cell phenotypes. Together, our results deduce insights into the molecular basis underlying KDM2A regulation of the biologically important methylated H3K36 mark. PMID- 25128497 TI - CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma. AB - One-year survival rates for newly diagnosed hepatocellular carcinoma (HCC) are <50%, and unresectable HCC carries a dismal prognosis owing to its aggressiveness and the undruggable nature of its main genetic drivers. By screening a custom library of shRNAs directed toward known drug targets in a genetically defined Myc driven HCC model, we identified cyclin-dependent kinase 9 (Cdk9) as required for disease maintenance. Pharmacological or shRNA-mediated CDK9 inhibition led to robust anti-tumor effects that correlated with MYC expression levels and depended on the role that both CDK9 and MYC exert in transcription elongation. Our results establish CDK9 inhibition as a therapeutic strategy for MYC-overexpressing liver tumors and highlight the relevance of transcription elongation in the addiction of cancer cells to MYC. PMID- 25128498 TI - The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic localization of CENP-A. AB - Centromere identity and its epigenetic maintenance require the incorporation of a histone H3 variant called CENP-A at centromeres. CENP-A mislocalization to ectopic sites may disrupt chromatin-based processes and chromosome segregation, so it is important to uncover the mechanisms by which this variant is exclusively localized to centromeres. Here, we identify a role for the conserved chromatin modifying complex FACT (facilitates chromatin transcription/transactions) in preventing budding yeast CENP-A(Cse4) mislocalization to euchromatin by mediating its proteolysis. The Spt16 subunit of the FACT complex binds to Psh1 (Pob3/Spt16/histone), an E3 ubiquitin ligase that targets CENP-A(Cse4) for degradation. The interaction between Psh1 and Spt16 is critical for both CENP A(Cse4) ubiquitylation and its exclusion from euchromatin. We found that Psh1 cannot efficiently ubiquitylate CENP-A(Cse4) nucleosomes in vitro, suggesting that additional factors must facilitate CENP-A(Cse4) removal from chromatin in vivo. Consistent with this, a Psh1 mutant that cannot associate with FACT has a reduced interaction with CENP-A(Cse4) in vivo. Together, our data identify a previously unknown mechanism to maintain centromere identity and genomic stability through the FACT-mediated degradation of ectopically localized CENP A(Cse4). PMID- 25128501 TI - Retraction. PMID- 25128499 TI - Active enhancers are delineated de novo during hematopoiesis, with limited lineage fidelity among specified primary blood cells. AB - Tissues may adopt diverse strategies to establish specific transcriptional programs in daughter lineages. In intestinal crypts, enhancers for genes expressed in both major cell types appear broadly permissive in stem and specified progenitor cells. In blood, another self-renewing tissue, it is unclear when chromatin becomes permissive for transcription of genes expressed in distinct terminal lineages. Using chromatin immunoprecipitation (ChIP) combined with deep sequencing (ChIP-seq) to profile activating histone marks, we studied enhancer dynamics in primary mouse blood stem, progenitor, and specified cells. Stem and multipotent progenitor cells show scant H3K4me2 marking at enhancers bound by specific transcription factors in their committed progeny. Rather, enhancers are modulated dynamically and serially, with substantial loss and gain of H3K4me2, at each cellular transition. Quantitative analysis of these dynamics accurately modeled hematopoiesis according to Waddington's notion of epigenotypes. Delineation of enhancers in terminal blood lineages coincides with cell specification, and enhancers active in single lineages show well-positioned H3K4me2- and H3K27ac-marked nucleosomes and DNaseI hypersensitivity in other cell types, revealing limited lineage fidelity. These findings demonstrate that enhancer chronology in blood cells differs markedly from that in intestinal crypts. Chromatin dynamics in hematopoiesis provide a useful foundation to consider classical observations such as cellular reprogramming and multilineage locus priming. PMID- 25128502 TI - In silico prediction of major drug clearance pathways by support vector machines with feature-selected descriptors. AB - We have previously established an in silico classification method ("CPathPred") to predict the major clearance pathways of drugs based on an empirical decision with only four physicochemical descriptors-charge, molecular weight, octanol water distribution coefficient, and protein unbound fraction in plasma-using a rectangular method. In this study, we attempted to improve the prediction performance of the method by introducing a support vector machine (SVM) and increasing the number of descriptors. The data set consisted of 141 approved drugs whose major clearance pathways were classified into metabolism by CYP3A4, CYP2C9, or CYP2D6; organic anion transporting polypeptide-mediated hepatic uptake; or renal excretion. With the same four default descriptors as used in CPathPred, the SVM-based predictor (named "default descriptor SVM") resulted in higher prediction performance compared with a rectangular-based predictor judged by 10-fold cross-validation. Two SVM-based predictors were also established by adding some descriptors as follows: 1) 881 descriptors predicted in silico from the chemical structures of drugs in addition to 4 default descriptors ("885 descriptor SVM"); and 2) selected descriptors extracted by a feature selection based on a greedy algorithm with default descriptors ("feature selection SVM"). The prediction accuracies of the rectangular-based predictor, default descriptor SVM, 885 descriptor SVM, and feature selection SVM were 0.49, 0.60, 0.72, and 0.91, respectively, and the overall precision values for these four methods were 0.72, 0.77, 0.86, and 0.98, respectively. In conclusion, we successfully constructed SVM-based predictors with limited numbers of descriptors to classify the major clearance pathways of drugs in humans with high prediction performance. PMID- 25128500 TI - Incomplete replication generates somatic DNA alterations within Drosophila polytene salivary gland cells. AB - DNA replication remains unfinished in many Drosophila polyploid cells, which harbor disproportionately fewer copies of late-replicating chromosomal regions. By analyzing paired-end high-throughput sequence data from polytene larval salivary gland cells, we define 112 underreplicated (UR) euchromatic regions 60 480 kb in size. To determine the effects of underreplication on genome integrity, we analyzed anomalous read pairs and breakpoint reads throughout the euchromatic genome. Each UR euchromatic region contains many different deletions 10-500 kb in size, while very few deletions are present in fully replicated chromosome regions or UR zones from embryo DNA. Thus, during endocycles, stalled forks within UR regions break and undergo local repair instead of remaining stable and generating nested forks. As a result, each salivary gland cell contains hundreds of unique deletions that account for their copy number reductions. Similar UR regions and deletions were observed in ovarian DNA, suggesting that incomplete replication, fork breakage, and repair occur widely in polytene cells. UR regions are enriched in genes encoding immunoglobulin superfamily proteins and contain many neurally expressed and homeotic genes. We suggest that the extensive somatic DNA instability described here underlies position effect variegation, molds the structure of polytene chromosomes, and should be investigated for possible functions. PMID- 25128503 TI - Advance care planning: whose agenda is it anyway? PMID- 25128505 TI - Infections increase risk of arterial and venous thromboses in Danish patients with systemic lupus erythematosus: 5102 patient-years of followup. AB - OBJECTIVE: Infections and thromboses are known complications of systemic lupus erythematosus (SLE). We investigated if infectious episodes in patients with SLE were followed by an increased risk of thrombotic events. METHODS: A cohort of 571 patients with prevalent or incident SLE was followed for a mean of 8.9 +/- 7.6 years. All episodes of hospitalized infections or episodes of cutaneous herpes zoster as well as arterial and venous thrombotic events were identified by retrospective chart review and prospective updating of a clinical database. For time-dependent analyses adjusted for age, sex, and ever-presence of antiphospholipid antibodies, thrombotic events were classified as occurring during the time at risk of 1 year after an infection or during the remaining control observation time. RESULTS: Of 271 infections identified, 104 were respiratory, 41 cutaneous herpes zoster, and 126 others. Of 159 thromboses identified, 98 were arterial. Incidence for arterial and venous thromboses within 1 year after infection was 2.18% and 2.56%, respectively, compared to patients who never had an infection (0.58 and 0.67). The adjusted 1-year risk of arterial and venous thrombosis after any infection was increased [relative rate (RR) 2.5, 95% CI 1.4-4.6, and RR 2.8, 95% CI 1.3-5.9, respectively]. Venous thromboses were in particular more prevalent after respiratory infections (RR 5.4, 95% CI 2.3 13). CONCLUSION: The temporal associations observed in this study indicate that infections could be risk factors for arterial or venous thromboses in patients with SLE, although causality was not addressed by this study. PMID- 25128504 TI - Serum 14-3-3eta is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. AB - OBJECTIVE: Serum 14-3-3eta is a novel joint-derived proinflammatory mediator implicated in the pathogenesis of rheumatoid arthritis (RA). In our study, we assessed the diagnostic utility of 14-3-3eta and its association with standard clinical and serological measures. METHODS: A quantitative ELISA was used to assess 14-3-3eta levels. Early (n=99) and established patients with RA (n=135) were compared to all controls (n=385), including healthy subjects (n=189). The sensitivity, specificity, positive and negative predictive values of 14-3-3eta, and the likelihood ratios (LR) for RA were determined through receiver-operator curve analysis. The incremental value of adding 14-3-3eta to anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in diagnosing early and established RA was assessed. RESULTS: Serum 14-3-3eta differentiated established patients with RA from healthy individuals and all controls (p<0.0001). A serum 14 3-3eta cutoff of >=0.19 ng/ml delivered a sensitivity and specificity of 77% and 93%, respectively, with corresponding LR positivity of 10.4. At this cutoff in early RA, 64% of patients with early RA were positive for 14-3-3eta, with a corresponding specificity of 93% (LR+ of 8.6), while 59% and 57% were positive for ACPA or RF, respectively. When ACPA, RF, and 14-3-3eta positivity were used in combination, 77 of the 99 patients (78%) with early RA were positive for any 1 of the 3 markers. Serum 14-3-3eta did not correlate with C-reactive protein, erythrocyte sedimentation rate, or Disease Activity Score, but patients who were 14-3-3eta-positive had significantly worse disease. CONCLUSION: Serum 14-3-3eta is a novel RA mechanistic marker that is highly specific, associated with worse disease, and complements current markers, enabling a more accurate diagnosis of RA. PMID- 25128507 TI - Is HLA-B27 increased in patients diagnosed with undifferentiated arthritis? Results from the Leiden early arthritis cohort. AB - OBJECTIVE: Undifferentiated arthritis (UA) is a common form of arthritis. According to the Assessment of Spondyloarthritis international Society (ASAS) criteria for peripheral spondyloarthritis (pSpA), HLA-B27 can be used to help classify patients with pSpA. We tested whether HLA-B27 is increased in patients diagnosed with UA. METHODS: Prevalence of HLA-B27 was compared between healthy controls and patients with UA. SpA features were compared between HLA-B27 positive and -negative UA, and SpA. RESULTS: We found 10.1% of UA (38/375) versus 7.2% (403/5584) of controls were HLA-B27-positive (OR 1.5, 95% CI 1.0-2.1; p = 0.037). HLA-B27-positive patients with UA had more SpA features than HLA-B27 negative patients (mean 1.6, SD 1.0, and 0.9 SD 0.6; p < 0.001), but patients with SpA had significantly more SpA features (mean 4.5, SD 1.5; p < 0.001). Family history and preceding infection were features more common in HLA-B27 positive than in HLA-B27-negative UA (15.8% vs 1.3%, p = 0.04 and 15.8% vs 2.6%, p = 0.04). After HLA-B27 testing, 21 additional patients (5.6%) with UA could potentially have been classified with pSpA according to the ASAS criteria. CONCLUSION: HLA-B27 is more common in patients with UA than in controls. However, the yield of HLA-B27 testing in UA is low. Our results suggest that HLA-B27 testing should be reserved for patients with additional SpA features. PMID- 25128506 TI - Longterm followup of rituximab therapy in patients with rheumatoid arthritis: results from the Belgian MabThera in Rheumatoid Arthritis registry. AB - OBJECTIVE: Our study reports the results of the MIRA (MabThera In Rheumatoid Arthritis) registry, set up to collect data about clinical usage, patient profile, and retention of rituximab (RTX) treatment in daily clinical practice in Belgium. METHODS: Patients with active rheumatoid arthritis (RA) who failed at least 1 anti-tumor necrosis factor (anti-TNF) treatment were included in our study between November 2006 and October 2011. At baseline, demographics, medication, disease history, disease activity, rheumatoid factor (RF), and anticyclic citrullinated peptide antibodies (anti-CCP) status were recorded. Evolution of the 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate, retreatments, and reasons for therapy stop were followed prospectively. RESULTS: The MIRA registry included 649 patients, with mean disease duration of 12.8 +/- 0.4 years and DAS28 values at inclusion of 5.85 +/- 0.48. Patients received on average 2.82 +/- 0.07 (range 1-9) RTX treatments, over a mean followup period of 93.1 +/- 2.6 weeks. At database lock, 433 patients (66.7%) were still under RTX treatment, 182 (28.0%) had stopped treatment, and 34 (5.2%) were lost to followup. Ineffectiveness (n = 108, 59%) and safety concerns (n = 39, 22%) were the most frequent reasons for discontinuing RTX therapy. From 2006 to 2011, RTX practice patterns clearly evolved toward RTX being started in patients with a lower number of previously failed anti-TNF drugs and lower baseline DAS28 values. A lower number of previous anti-TNF drugs, and positivity for RF and anti-CCP, predicted more successful longterm treatment. RTX treatment provided adequate longterm disease control. CONCLUSION: In our daily practice study, RTX provided good longterm disease control and treatment retention in refractory patients with RA. Over the years, rheumatologists tended to start this treatment in patients with fewer previous anti-TNF treatments and lower disease activity. PMID- 25128508 TI - Percutaneous transluminal angioplasty for symptomatic pulmonary stenosis in Takayasu arteritis. AB - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of percutaneous transluminal angioplasty (PTA) for symptomatic pulmonary stenosis in Takayasu arteritis (TA). METHODS: From January 2009 to December 2012, clinical data of 14 patients [mean age 33.9 +/- 9.3 yrs; 11 patients female (78.6%)] with symptomatic pulmonary stenosis in TA underwent PTA and were analyzed prospectively. RESULTS: PTA was successfully performed in 22 lesions of 14 patients. Among those lesions, 18 were treated by PTA alone while the others were treated with stent implantation. Three patients (21.4%) had reperfusion pulmonary injury; 2 patients recovered completely while the other died of respiratory failure 3 days after the procedure. Mean pulmonary arterial pressure (PAP) decreased from 53.4 +/- 15.8 mmHg to 38.4 +/- 12.7 mmHg immediately after intervention (p < 0.001). After an average of 29 months of followup, the New York Heart Association functional class and 6-min walking distances improved while mean PAP measured by echocardiography decreased significantly (compared with baseline, all p < 0.01). One patient died of severe pulmonary infection and cardiac shock at 28 months after the procedure. CONCLUSION: The study showed that PTA improved subjective symptoms and objective variables of the patients with symptomatic pulmonary stenosis in TA, with an acceptable mortality. PTA may be a promising therapeutic strategy for symptomatic pulmonary stenosis in TA. PMID- 25128509 TI - Current smoking is associated with incident ankylosing spondylitis -- the HUNT population-based Norwegian health study. AB - OBJECTIVE: Smoking contributes to progression of ankylosing spondylitis (AS). Because smoking is also a risk factor for incident rheumatoid arthritis (RA) and psoriatic arthritis, our aim was to test whether smoking habits are associated with incident AS. METHODS: Using data from the HUNT health study of the entire adult population of Nord-Trondelag, Norway, participants in HUNT2 (1995-1997) and HUNT3 (2006-2008) were identified who reported a diagnosis of AS in HUNT3 but not in HUNT2 (n = 107). Incident AS cases were compared with AS-unaffected individuals (n = 35,278) in a case-control design. Participants with RA were excluded. RESULTS: Present smoking was significantly associated with incident self-reported AS in logistic regression adjusted for potential confounders (OR 1.99, 95% CI 1.28-3.11, p = 0.002). Previous smoking (OR 1.15, 95% CI 0.66-2.02, p = 0.62) or total pack-years at HUNT2 (OR 1.01, 95% CI 0.99-1.04, p = 0.21) were not significant. The association with present smoking remained significant in various sensitivity analyses: including only cases with high probability of true AS diagnosis (OR 1.82, 95% CI 1.03-3.19, p = 0.04); including only cases with AS reported more than 3-5 years after HUNT2 (OR 2.34, 95% CI 1.09-5.03, p = 0.029), or including only participants genotyped for HLA-B27 (94 cases and 859 controls) adjusting for genotype (OR 1.79, 95% CI 1.04-2.85, p = 0.033). Hypertension was also significantly associated with incident AS (OR from 1.65 to 2.81). CONCLUSION: In the HUNT population-based study, incident AS was associated with current smoking and hypertension. If verified in further studies, this suggests that smoking should be discouraged in those at a higher AS risk, e.g., with a family history or carrying HLA-B27. PMID- 25128510 TI - The effect of exercise on sleep and fatigue in rheumatoid arthritis: a randomized controlled study. AB - OBJECTIVE: Sleep disturbance and chronic fatigue are common in rheumatoid arthritis (RA) and contribute to disability, symptomatology, and healthcare use. It has long been recognized in other populations that exercise can improve sleep and diminish fatigue. The effect of exercise on sleep quality and fatigue in RA has not been evaluated. METHODS: Ours is a randomized controlled study in RA to determine the effect of an exercise program on sleep quality and fatigue. These were measured using the Pittsburgh Sleep Quality Index and the Fatigue Severity Scale. Patients were randomized to either a 12-week, home-based exercise intervention or usual care. The exercise program consisted of specific exercises to target individual deficiencies identified using the Health Assessment Questionnaire (HAQ) with cardiovascular work as per the guidelines. The intervention group was evaluated on a 3-week basis. Full evaluation was carried out at baseline and at 12 weeks. RESULTS: Forty patients were randomized to the intervention with 38 controls. In the exercise intervention group, there was a statistically significant improvement in HAQ (p = 0.00), pain (p = 0.05), stiffness (p = 0.05), sleep quality (p = 0.04), and fatigue (p = 0.04). In our control group, there was a statistically significant improvement demonstrated in their overall perceptions of the benefits of exercise, but none of the other variables. CONCLUSION: Our study demonstrates that an exercise program resulted in significant improvement in sleep quality and fatigue. This is particularly interesting given the importance of fatigue as an outcome measure in RA and gives us yet another reason to prescribe exercise in this population. PMID- 25128511 TI - MicroRNA profiling in Chinese patients with primary Sjogren syndrome reveals elevated miRNA-181a in peripheral blood mononuclear cells. AB - OBJECTIVE: Characterized by chronic inflammation, dysfunction of exocrine glands, and systemic autoimmunity, primary Sjogren syndrome (pSS) is a common autoimmune disease in elderly women. Our study was performed to explore the potential involvement of microRNA (miRNA) in Chinese patients with pSS. METHODS: Using microarrays, miRNA expression in peripheral blood mononuclear cells (PBMC) was profiled in 4 female patients with pSS and 3 healthy participants, followed by a large-scale study of 33 patients and 10 healthy individuals. Compared to the healthy participants, 202 miRNA were upregulated and 180 were downregulated in the patients with pSS. To confirm this finding, a set of regulated miRNA was further examined in a large patient group, using quantitative reverse transcriptase-PCR assays. RESULTS: MiR-181a was the miRNA that most profoundly differed between patients with pSS and healthy individuals; however, similar miRNA-181a expression profiles were found in groups with different disease phenotypes. Together, these observations suggested that an elevated miRNA-181a level is a general phenomenon in Chinese patients with pSS. CONCLUSION: In addition to the elevated miR-181a levels, our study led to the speculation that elevated miR-181a levels in the PBMC of these patients compromise the maturation of B cells, enabling them to recognize and attack autoantigens and resulting in disease phenotypes. In addition to the regulation of human miRNA, many virus derived miRNA were unexpectedly upregulated in the patients with pSS, suggesting that viral infection of PBMC plays a role in this disease. PMID- 25128512 TI - Predictors of incident depression in systemic lupus erythematosus. AB - OBJECTIVE: Findings from previous studies of predictors of depression among patients with systemic lupus erythematosus (SLE) have been inconsistent. The aim of our study was to identify risk factors that preceded incident depression based on a large, closely followed longitudinal cohort. METHODS: Data regarding 1609 patients with SLE in the Hopkins Lupus Cohort who had no history of depression prior to cohort entry were analyzed. Demographic variables, SLE manifestations, laboratory tests, physician's global assessment, Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), cumulative organ damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), and onset of depression were recorded at enrollment and each quarterly visit. Rates of incident depression were calculated overall, and in subgroups defined by demographic and clinical variables. Adjusted estimates of association were derived using pooled logistic regression. RESULTS: The incidence of depression was 29.7 episodes per 1000 person-years. In the multivariable analysis, these variables remained as independent predictors of incident depression: recent SLE diagnosis, non-Asian ethnicity, disability, cutaneous activity, longitudinal myelitis, and current prednisone use of 20 mg/day or higher. Global disease activity (SELENA-SLEDAI) was not a significant predictor after controlling for prednisone use. CONCLUSION: Depression in SLE is multifactorial. Higher-dose prednisone (>= 20 mg daily) is 1 important independent risk factor. Global disease activity is not a risk factor, but cutaneous activity and certain types of neurologic activity (myelitis) are predictive of depression. The independent effect of prednisone provides clinicians with an additional incentive to avoid and reduce high-dose prednisone exposure in SLE. PMID- 25128513 TI - Tocilizumab treatment increases left ventricular ejection fraction and decreases left ventricular mass index in patients with rheumatoid arthritis without cardiac symptoms: assessed using 3.0 tesla cardiac magnetic resonance imaging. AB - OBJECTIVE: The aim of our pilot study was to prospectively evaluate the effect of inhibiting interleukin 6 on the left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA) without cardiac symptoms, using cardiac magnetic resonance (CMR). METHODS: Female patients with RA with active disease and healthy controls were enrolled. Cardiac symptoms were absent in all subjects. Tocilizumab (TCZ; 8 mg/kg IV every 4 weeks) was prescribed for patients with RA with an inadequate clinical response to methotrexate. All subjects underwent baseline evaluation of LV function and structure measured by CMR. We compared measures of LV geometry and function between patients with RA and patients without RA controls at baseline, and changes in the same variables between baseline and after 52 weeks of treatment among the group with RA. RESULTS: Twenty women with RA were compared with 20 women without RA of similar mean age. In patients with RA at baseline, ejection fraction (EF) was significantly lower ( 3.7%) and LV mass index (LVMI) significantly higher (+9.2%) compared with controls. TCZ treatment resulted in a significant decrease in the Simplified Disease Activity Index (SDAI) after 52 weeks of treatment, paralleling a significant increase in EF (+8.2%) and a significant decrease in LVMI (-24.4%) over the same period. The percentage change in LVMI correlated strongly with the percentage change in SDAI (r = -0.63, p = 0.0028). LV geometry in the group with RA at baseline showed eccentric hyper-trophy compared with the group without RA, a condition that normalized after TCZ treatment. CONCLUSION: TCZ treatment significantly increased EF and decreased LVMI associated with disease activity. PMID- 25128514 TI - Responsiveness of magnetic resonance imaging-derived measures over 2.7 years. AB - OBJECTIVE: To compare the responsiveness of magnetic resonance imaging (MRI) derived measures of knee osteoarthritis over 2.7 years. METHODS: There were 430 community-based participants (mean age 63.0 yrs, range 51-79 yrs; 51% female) measured at baseline and 2.7 years later. MRI of the right knee at both timepoints was performed to assess cartilage volume, cartilage defects, bone marrow lesions (BML), meniscal pathology, and tibial bone area. Global measurements were calculated as the sum of tibial and femoral measures. Standardized response mean (SRM) was calculated as the mean of change divided by the SD of change. RESULTS: Global tibiofemoral cartilage volume and cartilage defects had the best SRM of -0.80 and 0.62, respectively. Site-specific measurements were lower (SRM range for cartilage volume -0.48 to -0.54 and cartilage defects 0.33 to 0.49). The SRM for BML was 0.12, meniscal pathology 0.39, and tibial bone area -0.09. Cartilage volume and/or defects tended to be more responsive in those with knee pain, those who were obese, those who were older, and those with radiographic osteoarthritis. CONCLUSION: Global cartilage volume demonstrated the best sensitivity to change, suggesting that if we relied solely on SRM to optimize clinical trial design, then cartilage volume would be the best outcome measure. However, clinical trials have shown that cartilage volume may be less responsive to treatment compared to other measures that have lower SRM (such as BML). Therefore, although one can optimize trial efficiency by finding more responsive endpoints, both sensitivity to change and magnitude of benefit should be considered. PMID- 25128515 TI - Reduced ovarian reserve in patients with Takayasu arteritis. AB - OBJECTIVE: To assess ovarian reserve markers in patients with Takayasu arteritis (TA). METHODS: Twenty patients with TA and 24 healthy controls were evaluated for ovarian reserve by follicle-stimulating hormone, luteinizing hormone, and estradiol, and antral follicle count (AFC). Anti-Mullerian hormone (AMH) was measured by ELISA using 2 different kits. Demographical data, menstrual abnormalities, disease variables, and treatment were also analyzed. RESULTS: The median current age was similar in patients with TA and controls (31.2 +/- 6.1 vs 30.4 +/- 6.9 yrs, p = 0.69). The frequencies of decreased levels of AMH in patients with TA were identical using both kits and higher when compared to controls (50% vs 17%, p = 0.02; 50% vs 19%, p = 0.048). A positive correlation was observed between the 2 kits in patients with TA (r = +0.93, p < 0.0001) and in healthy controls (r = +0.93, p < 0.0001). The apparent lower AFC (11 vs 16, p = 0.13) and the higher frequency of low AFC (41% vs 22%, p = 0.29) in TA compared to controls did not reach statistical significance. Other hormones were similar in both groups (p > 0.05). Further evaluation of patients with TA with low AMH levels (< 1.0 ng/ml) versus normal AMH levels (> 1.0 ng/ml) revealed that the frequency of current disease activity (p = 1.0) and the median of erythrocyte sedimentation rate (p = 0.6), C-reactive protein (p = 0.4), prednisone cumulative dose (p = 0.8), and methotrexate cumulative dose (p = 0.8) were comparable in both groups. Cyclophosphamide use was reported in only 1 patient with reduced ovarian reserve, whereas none of the remaining patients received gonadotoxic drugs. CONCLUSION: To the best of our knowledge, our present study was the first to suggest that patients with TA may have diminished ovarian reserve. PMID- 25128516 TI - Persistence and dose escalation of tumor necrosis factor inhibitors in US veterans with rheumatoid arthritis. AB - OBJECTIVE: Limited evidence exists comparing the persistence, effectiveness, and costs of biologic therapies for rheumatoid arthritis in clinical practice. Comparative effectiveness studies are needed to understand real-world experience with these agents. We evaluated treatment patterns, costs, and effectiveness of tumor necrosis factor inhibitor (TNFi) agents in patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry. METHODS: Observational data from the VARA registry and linked administrative databases were analyzed. Longitudinal data from VARA patients initiating adalimumab (ADA), etanercept (ETN), or infliximab (IFX) from 2003 (the date all agents were available within the Veteran Affairs) to 2010 were analyzed. Outcomes included Disease Activity Score using 28 joints (DAS28), treatment persistence, dose escalation, and direct costs of drugs and drug administration. RESULTS: For 563 eligible patients, baseline DAS28, DAS28 improvements, and persistence on initial treatment were similar across agents. Fewer patients receiving ETN (n = 5/290; 2%) underwent dose escalation than did patients taking ADA (n = 32/204; 16%) or IFX (n = 44/69; 64%). Annual costs for first course of TNFi therapy were lower for injectable ADA ($13,100 US) and ETN ($13,500 US) than for intravenously administered IFX ($16,900 US). CONCLUSION: Despite similar persistence and clinical disease activity for these TNFi agents, rates of dose escalation were highest with ADA and IFX. Higher overall costs were noted for IFX without increases in effectiveness. PMID- 25128517 TI - Mortality, recurrence, and hospital course of patients with systemic sclerosis related acute intestinal pseudo-obstruction. AB - OBJECTIVE: Acute intestinal pseudo-obstruction is a rare gastrointestinal manifestation of systemic sclerosis (SSc) with few data existing as to its demographics, clinical course, outcomes, and mortality. METHODS: We undertook a case-control study to describe 64 cases in 37 unique patients, of whom 70% had spontaneous resolution with conservative measures of intravenous hydration and bowel rest, 9% underwent surgical resection, and 25% required prolonged total parenteral nutrition (TPN). RESULTS: Hospital course was for a mean of 12 +/- 12.5 days and there was a 16% patient mortality in our population. In a subgroup analysis, patients who had recurrent episodes of pseudo-obstruction were less likely to have esophageal involvement from SSc, and more likely to need prolonged TPN. Mortality tended to be higher in male patients and patients who did not have SSc-related esophageal involvement, and also in patients who had low hemoglobin and serum albumin at presentation. The need for a nasogastric tube for decompression and a surgical intervention correlated with a more prolonged hospital stay. CONCLUSION: To the best of our knowledge, ours is the largest study looking at this rare manifestation of SSc. PMID- 25128518 TI - A multibiomarker disease activity score for rheumatoid arthritis predicts radiographic joint damage in the BeSt study. AB - OBJECTIVE: To determine whether a multibiomarker disease activity (MBDA) score predicts radiographic damage progression in the subsequent year in patients with early rheumatoid arthritis. METHODS: There were 180 serum samples available in the BeSt study (trial numbers NTR262, NTR 265): 91 at baseline (84 with radiographs available) and 89 at 1-year followup (81 with radiographs available). Radiographs were assessed using the Sharp/van der Heijde Score (SvdH). Twelve serum biomarkers were measured to determine MBDA scores using a validated algorithm. Receiver-operating curves and Poisson regression analyses were performed, with Disease Activity Score (DAS) and MBDA score as independent variables, and radiographic progression as dependent variable. RESULTS: At baseline, MBDA scores discriminated more between patients who developed radiographic progression (increase in SvdH>=5 points) and patients who did not [area under the curve (AUC) 0.767, 95% CI 0.639-0.896] than did DAS (AUC 0.521, 95% CI 0.358-0.684). At 1 year, MBDA score had an AUC of 0.691 (95% CI 0.453 0.929) and DAS had an AUC of 0.649 (95% CI 0.417-0.880). Adjusted for anticitrullinated protein antibody status and DAS, higher MBDA scores were associated with an increased risk for SvdH progression [relative risk (RR) 1.039, 95% CI 1.018-1.059 for baseline MBDA score; 1.037, 95% CI 1.009-1.065 for Year 1 MBDA score]. Categorized high MBDA scores were also correlated with SvdH progression (RR for high MBDA score at baseline 3.7; low or moderate MBDA score as reference). At 1 year, high MBDA score gave a RR of 4.6 compared to low MBDA score. CONCLUSION: MBDA scores predict radiographic damage progression at baseline and during disease course. PMID- 25128519 TI - Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion. AB - OBJECTIVE: Primary gout has been associated with single-nucleotide polymorphisms (SNP) in several tubular urate transporter genes. No study has assessed the association of reabsorption and secretion urate transporter gene SNP with gout in a single cohort of documented primary patients with gout carefully subclassified as normoexcretors or underexcretors. METHODS: Three reabsorption SNP (SLC22A12/URAT1, SLC2A9/GLUT9, and SLC22A11/OAT4) and 2 secretion transporter SNP (SLC17A1/NPT1 and ABCG2/BRCP) were studied in 104 patients with primary gout and in 300 control subjects. The patients were subclassified into normoexcretors and underexcretors according to their serum and 24-h urinary uric acid levels under strict conditions of dietary control. RESULTS: Compared with control subjects, patients with gout showed different allele distributions of the 5 SNP analyzed. However, the diagnosis of underexcretor was only positively associated with the presence of the T allele of URAT1 rs11231825, the G allele of GLUT9 rs16890979, and the A allele of ABCG2 rs2231142. The association of the A allele of ABCG2 rs2231142 in normoexcretors was 10 times higher than in underexcretors. The C allele of NPT1 rs1165196 was only significantly associated with gout in patients with normal uric acid excretion. CONCLUSION: Gout with uric acid underexcretion is associated with transporter gene SNP related mainly to tubular reabsorption, whereas uric acid normoexcretion is associated only with tubular secretion SNP. This finding supports the concept of distinctive mechanisms to account for hyperuricemia in patients with gout with reduced or normal uric acid excretion. PMID- 25128520 TI - When to adjust therapy in patients with rheumatoid arthritis after initiation of etanercept plus methotrexate or methotrexate alone: findings from a randomized study (COMET). AB - OBJECTIVE: The objective of these posthoc analyses was to evaluate short-term clinical outcomes as predictors of poor response after 1 year of treatment with combination etanercept/methotrexate (ETN/MTX) therapy versus MTX monotherapy in patients with early rheumatoid arthritis (RA). METHODS: Participants with moderate to severe RA [28-joint Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) >= 3.2] of 3-24 months' duration received ETN 50 mg weekly plus MTX or MTX monotherapy for 52 weeks. Regression analyses were performed to evaluate the likelihood of remission (DAS28-ESR < 2.6) after 1 year despite poor clinical short-term treatment effects (e.g., absolute or changes from baseline in DAS28-ESR after 4, 8, 12, 20, and 24 weeks of therapy). RESULTS: The magnitude of disease activity and its improvement and timing influenced remission probability in both treatment groups; remission rate was diminished with higher disease activity levels and lower response levels over time from weeks 4 to 24. The rate of DAS28-ESR remission at 1 year was generally greater with ETN/MTX than with MTX alone at most timepoints from weeks 4 to 24. Despite persistent high disease activity (DAS28-ESR > 5.1) after 4, 8, 12, and 24 weeks of therapy, 35%, 27%, 25%, and 22% of patients, respectively, in the ETN/MTX group achieved DAS28-ESR remission after 1 year of continuous treatment; the respective proportions were 33%, 27%, 8%, and 13% in the MTX group. CONCLUSION: High disease activity and less improvement with treatment over time in the initial 24 weeks of treatment, particularly after 12 weeks, were predictive of a lower remission rate after 1 year. PMID- 25128521 TI - Cigarette smoke-induced iBALT mediates macrophage activation in a B cell dependent manner in COPD. AB - Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures and macrophages accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear. Here, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to an increased size and number of iBALT structures, and increased lung compliance and mean linear chord length in wild-type (WT) but not in B cell-deficient mice. The increased accumulation of lung resident macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated MMP12 expression. In vitro coculture experiments using B cells and macrophages demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12 upregulation, which could be inhibited by an anti-IL-10 antibody. In summary, B cell function in iBALT formation seems necessary for macrophage activation and tissue destruction in CS-induced emphysema and possibly provides a new target for therapeutic intervention in COPD. PMID- 25128522 TI - PKG-1alpha leucine zipper domain defect increases pulmonary vascular tone: implications in hypoxic pulmonary hypertension. AB - Pulmonary hypertension (PH) is a chronic disease characterized by a progressive increase in vasomotor tone, narrowing of the vasculature with structural remodeling, and increase in pulmonary vascular resistance. Current treatment strategies include nitric oxide therapy and methods to increase cGMP-mediated vasodilatation. cGMP-dependent protein kinases (PKG) are known mediators of nitric oxide- and cGMP-induced vasodilatation. Deletion of PKG-1 in mice has been shown to induce PH, however, the exact mechanisms by which loss of PKG-1 function leads to PH is not known. In a mouse model with a selective mutation in the NH2 terminus leucine zipper protein interaction domain of PKG-1alpha [leucine zipper mutant (LZM)], we found a progressive increase in right ventricular systolic pressure and right heart hypertrophy compared with wild-type (WT) mice and increased RhoA-GTPase activity in the lungs. When exposed to chronic hypoxia, LZM mice developed modestly enhanced right ventricular remodeling compared with WT mice. Tadalafil, a phosphodiesterase-5 inhibitor that increases cGMP levels, significantly attenuated hypoxia-induced cardiopulmonary remodeling in WT mice but had no effect in LZM mice. We conclude that a functional leucine zipper domain in PKG-1alpha is essential for maintenance of a low pulmonary vascular tone in normoxia and for cGMP-mediated beneficial effects of phosphodiesterase-5 inhibition in hypoxic cardiopulmonary remodeling. PMID- 25128523 TI - Real-time monitoring of endogenous lipid peroxidation by exhaled ethylene in patients undergoing cardiac surgery. AB - Pulmonary and systemic organ injury produced by oxidative stress including lipid peroxidation is a fundamental tenet of ischemia-reperfusion injury, inflammatory response to cardiac surgery, and cardiopulmonary bypass (CPB) but is not routinely measured in a surgically relevant time frame. To initiate a paradigm shift toward noninvasive and real-time monitoring of endogenous lipid peroxidation, we have explored pulmonary excretion and dynamism of exhaled breath ethylene during cardiac surgery to test the hypothesis that surgical technique and ischemia-reperfusion triggers lipid peroxidation. We have employed laser photoacoustic spectroscopy to measure real-time trace concentrations of ethylene from the patient breath and from the CPB machine. Patients undergoing aortic or mitral valve surgery-requiring CPB (n = 15) or off-pump coronary artery bypass surgery (OPCAB) (n = 7) were studied. Skin and tissue incision by diathermy caused striking (> 30-fold) increases in exhaled ethylene resulting in elevated levels until CPB. Gaseous ethylene in the CPB circuit was raised upon the establishment of CPB (> 10-fold) and decreased over time. Reperfusion of myocardium and lungs did not appear to enhance ethylene levels significantly. During OPCAB surgery, we have observed increased ethylene in 16 of 30 documented reperfusion events associated with coronary and aortic anastomoses. Therefore, novel real-time monitoring of endogenous lipid peroxidation in the intraoperative setting provides unparalleled detail of endogenous and surgery-triggered production of ethylene. Diathermy and unprotected regional myocardial ischemia and reperfusion are the most significant contributors to increased ethylene. PMID- 25128524 TI - Role of hypoxia-induced transglutaminase 2 in pulmonary artery smooth muscle cell proliferation. AB - We previously reported that transglutaminase 2 (TG2) activity is markedly elevated in lungs of hypoxia-exposed rodent models of pulmonary hypertension (PH). Since vascular remodeling of pulmonary artery smooth muscle cells (PASMCs) is important in PH, we undertook the present study to determine whether TG2 activity is altered in PASMCs with exposure to hypoxia and whether that alteration participates in their proliferative response to hypoxia. Cultured distal bovine (b) and proximal human (h) PASMCs were exposed to hypoxia (3% O2) or normoxia (21% O2). mRNA and protein expression were determined by PCR and Western blot analyses. TG2 activity and function were visualized and determined by fluorescent labeled 5-pentylamine biotin incorporation and immunoblotting of serotonylated fibronectin. Cell proliferation was assessed by [(3)H]thymidine incorporation assay. At 24 h, both TG2 expression and activity were stimulated by hypoxia in bPASMCs. Activation of TG2 by hypoxia was blocked by inhibition of the extracellular calcium-sensing receptor or the transient receptor potential channel V4. In contrast, TG2 expression was blocked by inhibition of the transcription factor hypoxia-inducible factor-1alpha, supporting the presence of separate mechanisms for stimulation of activity and expression of TG2. Pulmonary arterial hypertension patient-derived hPASMCs were found to proliferate significantly more rapidly and respond to hypoxia more strongly than control derived hPASMCs. Similar to bovine cells, hypoxia-induced proliferation of patient-derived cells was blocked by inhibition of TG2 activity. Our results suggest an important role for TG2, mediated by intracellular calcium fluxes and HIF-1alpha, in hypoxia-induced PASMC proliferation and possibly in vascular remodeling in PH. PMID- 25128525 TI - Genetic interactions between planar cell polarity genes cause diverse neural tube defects in mice. AB - Neural tube defects (NTDs) are among the commonest and most severe forms of developmental defect, characterized by disruption of the early embryonic events of central nervous system formation. NTDs have long been known to exhibit a strong genetic dependence, yet the identity of the genetic determinants remains largely undiscovered. Initiation of neural tube closure is disrupted in mice homozygous for mutations in planar cell polarity (PCP) pathway genes, providing a strong link between NTDs and PCP signaling. Recently, missense gene variants have been identified in PCP genes in humans with NTDs, although the range of phenotypes is greater than in the mouse mutants. In addition, the sequence variants detected in affected humans are heterozygous, and can often be detected in unaffected individuals. It has been suggested that interactions between multiple heterozygous gene mutations cause the NTDs in humans. To determine the phenotypes produced in double heterozygotes, we bred mice with all three pairwise combinations of Vangl2(Lp), Scrib(Crc) and Celsr1(Crsh) mutations, the most intensively studied PCP mutants. The majority of double-mutant embryos had open NTDs, with the range of phenotypes including anencephaly and spina bifida, therefore reflecting the defects observed in humans. Strikingly, even on a uniform genetic background, variability in the penetrance and severity of the mutant phenotypes was observed between the different double-heterozygote combinations. Phenotypically, Celsr1(Crsh);Vangl2(Lp);Scrib(Crc) triply heterozygous mutants were no more severe than doubly heterozygous or singly homozygous mutants. We propose that some of the variation between double-mutant phenotypes could be attributed to the nature of the protein disruption in each allele: whereas Scrib(Crc) is a null mutant and produces no Scrib protein, Celsr1(Crsh) and Vangl2(Lp) homozygotes both express mutant proteins, consistent with dominant effects. The variable outcomes of these genetic interactions are of direct relevance to human patients and emphasize the importance of performing comprehensive genetic screens in humans. PMID- 25128527 TI - Subdomain II of alpha-isopropylmalate synthase is essential for activity: inferring a mechanism of feedback inhibition. AB - The committed step of leucine biosynthesis, converting acetyl-CoA and alpha ketoisovalerate into alpha-isopropylmalate, is catalyzed by alpha-isopropylmalate synthase (IPMS), an allosteric enzyme subjected to feedback inhibition by the end product L-leucine. We characterized the short form IPMS from Leptospira biflexa (LbIPMS2), which exhibits a catalytic activity comparable with that of the long form IPMS (LbIPMS1) and has a similar N-terminal domain followed by subdomain I and subdomain II but lacks the whole C-terminal regulatory domain. We found that partial deletion of the regulatory domain of LbIPMS1 resulted in a loss of about 50% of the catalytic activity; however, when the regulatory domain was deleted up to Arg-385, producing a protein that is almost equivalent to the intact LbIPMS2, about 90% of the activity was maintained. Moreover, in LbIPMS2 or LbIPMS1, further deletion of several residues from the C terminus of subdomain II significantly impaired or completely abolished the catalytic activity, respectively. These results define a complete and independently functional catalytic module of IPMS consisting of both the N-terminal domain and the two subdomains. Structural comparison of LbIPMS2 and the Mycobacterium tuberculosis IPMS revealed two different conformations of subdomain II that likely represent two substrate-binding states related to cooperative catalysis. The biochemical and structural analyses together with the previously published hydrogen-deuterium exchange data led us to propose a conformation transition mechanism for feedback inhibition mediated by subdomains I and II that might associated with alteration of the binding affinity toward acetyl-CoA. PMID- 25128526 TI - Cytoplasmic retention of protein phosphatase 2A inhibitor 2 (I2PP2A) induces Alzheimer-like abnormal hyperphosphorylation of Tau. AB - Abnormal hyperphosphorylation of Tau leads to the formation of neurofibrillary tangles, a hallmark of Alzheimer disease (AD), and related tauopathies. The phosphorylation of Tau is regulated by protein phosphatase 2A (PP2A), which in turn is modulated by endogenous inhibitor 2 (I2 (PP2A)). In AD brain, I2 (PP2A) is translocated from neuronal nucleus to cytoplasm, where it inhibits PP2A activity and promotes abnormal phosphorylation of Tau. Here we describe the identification of a potential nuclear localization signal (NLS) in the C-terminal region of I2 (PP2A) containing a conserved basic motif, (179)RKR(181), which is sufficient for directing its nuclear localization. The current study further presents an inducible cell model (Tet-Off system) of AD-type abnormal hyperphosphorylation of Tau by expressing I2 (PP2A) in which the NLS was inactivated by (179)RKR(181) -> AAA along with (168)KR(169) -> AA mutations. In this model, the mutant NLS (mNLS)-I2 (PP2A) (I2 (PP2A)AA-AAA) was retained in the cell cytoplasm, where it physically interacted with PP2A and inhibited its activity. Inhibition of PP2A was associated with the abnormal hyperphosphorylation of Tau, which resulted in microtubule network instability and neurite outgrowth impairment. Expression of mNLS-I2 (PP2A) activated CAMKII and GSK-3beta, which are Tau kinases regulated by PP2A. The immunoprecipitation experiments showed the direct interaction of I2 (PP2A) with PP2A and GSK-3beta but not with CAMKII. Thus, the cell model provides insights into the nature of the potential NLS and the mechanistic relationship between I2 (PP2A)-induced inhibition of PP2A and hyperphosphorylation of Tau that can be utilized to develop drugs preventing Tau pathology. PMID- 25128528 TI - Structural and mechanistic insight into the Listeria monocytogenes two-enzyme lipoteichoic acid synthesis system. AB - Lipoteichoic acid (LTA) is an important cell wall component required for proper cell growth in many Gram-positive bacteria. In Listeria monocytogenes, two enzymes are required for the synthesis of this polyglycerolphosphate polymer. The LTA primase LtaP(Lm) initiates LTA synthesis by transferring the first glycerolphosphate (GroP) subunit onto the glycolipid anchor and the LTA synthase LtaS(Lm) extends the polymer by the repeated addition of GroP subunits to the tip of the growing chain. Here, we present the crystal structures of the enzymatic domains of LtaP(Lm) and LtaS(Lm). Although the enzymes share the same fold, substantial differences in the cavity of the catalytic site and surface charge distribution contribute to enzyme specialization. The eLtaS(Lm) structure was also determined in complex with GroP revealing a second GroP binding site. Mutational analysis confirmed an essential function for this binding site and allowed us to propose a model for the binding of the growing chain. PMID- 25128529 TI - Dual role of the Trps1 transcription factor in dentin mineralization. AB - TRPS1 (tricho-rhino-phalangeal syndrome) is a unique GATA-type transcription factor that acts as a transcriptional repressor. TRPS1 deficiency and dysregulated TRPS1 expression result in skeletal and dental abnormalities implicating TRPS1 in endochondral bone formation and tooth development. Moreover, patients with tricho-rhino-phalangeal syndrome frequently present with low bone mass indicating TRPS1 involvement in bone homeostasis. In addition, our previous data demonstrated accelerated mineralization of the perichondrium in Trps1 mutant mice and impaired dentin mineralization in Col1a1-Trps1 transgenic mice, implicating Trps1 in the mineralization process. To understand the role of Trps1 in the differentiation and function of cells producing mineralized matrix, we used a preodontoblastic cell line as a model of dentin mineralization. We generated both Trps1-deficient and Trps1-overexpressing stable cell lines and analyzed the progression of mineralization by alkaline phosphatase and alizarin red staining. As predicted, based on our previous in vivo data, delayed and decreased mineralization of Trps1-overexpressing odontoblastic cells was observed when compared with control cells. This was associated with down-regulation of genes regulating phosphate homeostasis. Interestingly, Trps1-deficient cells lost the ability to mineralize and demonstrated decreased expression of several genes critical for initiating the mineralization process, including Alpl and Phospho1. Based on these data, we have concluded that Trps1 serves two critical and context dependent functions in odontoblast-regulated mineralization as follows: 1) Trps1 is required for odontoblast maturation by supporting expression of genes crucial for initiating the mineralization process, and 2) Trps1 represses the function of mature cells and, consequently, restricts the extent of extracellular matrix mineralization. PMID- 25128530 TI - Phosphatase CD45 both positively and negatively regulates T cell receptor phosphorylation in reconstituted membrane protein clusters. AB - T cell receptor (TCR) phosphorylation requires the kinase Lck and phosphatase CD45. CD45 activates Lck by dephosphorylating an inhibitory tyrosine of Lck to relieve autoinhibition. However, CD45 also dephosphorylates the TCR, and the spatial exclusion of CD45 from TCR clustering in the plasma membrane appears to attenuate this negative effect of CD45. To further investigate the role of CD45 in signal initiation, we reconstituted membrane TCR clusters in vitro on supported lipid bilayers. Fluorescence microscopy of single clusters showed that incorporation of CD45 enhanced phosphorylation of TCR clusters, but only when Lck co-clustered with TCR. We found that clustered Lck autophosphorylated the inhibitory tyrosine and thus could be activated by CD45, whereas diffusive Lck molecules did not. In the TCR-Lck clusters and at low CD45 density, we speculate that the effect of Lck activation may overcome dephosphorylation of TCR, resulting in a net positive regulation. The CD45 density in physiological TCR clusters is also low because of the exclusion of CD45. Thus, we propose that the spatial organization of TCR/Lck/CD45 in T cell membranes is important not only for modulating the negative role of CD45 but also for creating conditions in which CD45 has a positive role in signal initiation. PMID- 25128531 TI - The crystal structure of the plant small GTPase OsRac1 reveals its mode of binding to NADPH oxidase. AB - Rac/Rop proteins are Rho-type small GTPases that act as molecular switches in plants. Recent studies have identified these proteins as key components in many major plant signaling pathways, such as innate immunity, pollen tube growth, and root hair formation. In rice, the Rac/Rop protein OsRac1 plays an important role in regulating the production of reactive oxygen species (ROS) by the NADPH oxidase OsRbohB during innate immunity. However, the molecular mechanism by which OsRac1 regulates OsRbohB remains unknown. Here, we report the crystal structure of OsRac1 complexed with the non-hydrolyzable GTP analog guanosine 5'-(beta,gamma imido)triphosphate at 1.9 A resolution; this represents the first active-form structure of a plant small GTPase. To elucidate the ROS production in rice cells, structural information was used to design OsRac1 mutants that displayed reduced binding to OsRbohB. Only mutations in the OsRac1 Switch I region showed attenuated interactions with OsRbohB in vitro. In particular, Tyr(39) and Asp(45) substitutions suppressed ROS production in rice cells, indicating that these residues are critical for interaction with and activation of OsRbohB. Structural comparison of active-form OsRac1 with AtRop9 in its GDP-bound inactive form showed a large conformational difference in the vicinity of these residues. Our results provide new insights into the molecular mechanism of the immune response through OsRac1 and the various cellular responses associated with plant Rac/Rop proteins. PMID- 25128532 TI - Reduced plasminogen binding and delayed activation render gamma'-fibrin more resistant to lysis than gammaA-fibrin. AB - Fibrin (Fn) clots formed from gamma'-fibrinogen (gamma'-Fg), a variant with an elongated gamma-chain, are resistant to lysis when compared with clots formed from the predominant gammaA-Fg, a finding previously attributed to differences in clot structure due to delayed thrombin-mediated fibrinopeptide (FP) B release or impaired cross-linking by factor XIIIa. We investigated whether slower lysis of gamma'-Fn reflects delayed plasminogen (Pg) binding and/or activation by tissue plasminogen activator (tPA), reduced plasmin-mediated proteolysis of gamma'-Fn, and/or altered cross-linking. Clots formed from gamma'-Fg lysed more slowly than those formed from gammaA-Fg when lysis was initiated with tPA/Pg when FPA and FPB were both released, but not when lysis was initiated with plasmin, or when only FPA was released. Pg bound to gamma'-Fn with an association rate constant 22% lower than that to gammaA-Fn, and the lag time for initiation of Pg activation by tPA was longer with gamma'-Fn than with gammaA-Fn. Once initiated, however, Pg activation kinetics were similar. Factor XIIIa had similar effects on clots formed from both Fg isoforms. Therefore, slower lysis of gamma'-Fn clots reflects delayed FPB release, which results in delayed binding and activation of Pg. When clots were formed from Fg mixtures containing more than 20% gamma'-Fg, the upper limit of the normal level, the delay in lysis was magnified. These data suggest that circulating levels of gamma'-Fg modulate the susceptibility of clots to lysis by slowing Pg activation by tPA and provide another example of the intimate connections between coagulation and fibrinolysis. PMID- 25128533 TI - A review on human reinstatement studies: an overview and methodological challenges. AB - In human research, studies of return of fear (ROF) phenomena, and reinstatement in particular, began only a decade ago and recently are more widely used, e.g., as outcome measures for fear/extinction memory manipulations (e.g., reconsolidation). As reinstatement research in humans is still in its infancy, providing an overview of its stability and boundary conditions and summarizing methodological challenges is timely to foster fruitful future research. As a translational endeavor, clarifying the circumstances under which (experimental) reinstatement occurs may offer a first step toward understanding relapse as a clinical phenomenon and pave the way for the development of new pharmacological or behavioral ways to prevent ROF. The current state of research does not yet allow pinpointing these circumstances in detail and we hope this review will aid the research field to advance in this direction. As an introduction, we begin with a synopsis of rodent work on reinstatement and theories that have been proposed to explain the findings. The review however mainly focuses on reinstatement in humans. We first describe details and variations of the experimental setup in reinstatement studies in humans and give a general overview of results. We continue with a compilation of possible experimental boundary conditions and end with the role of individual differences and behavioral and/or pharmacological manipulations. Furthermore, we compile important methodological and design details on the published studies in humans and end with open research questions and some important methodological and design recommendations as a guide for future research. PMID- 25128535 TI - Impact of conscious intent on chunking during motor learning. AB - Humans and other mammals learn sequences of movements by splitting them into smaller "chunks." Such chunks are defined by the faster speed of performance of groups of movements. The purpose of this report is to determine how conscious intent to learn impacts chunking, an issue that remains unknown. Here, we studied 80 subjects who either with or without conscious intent learned a motor sequence. Performance was tested before and up to 1-wk post-training. Chunk formation, carryover of chunks, and concatenation of chunks into longer chunks, all measures of motor chunking success, were determined at each time-point. We found that formation, carryover, and concatenation of chunks were comparable across groups and did not improve over the training session and subsequent testing times. Thus, motor learning progressed in the absence of improvements in chunking irrespective of conscious intent. These data suggest that mechanisms other than chunking contribute to successful motor learning with and without conscious intent. PMID- 25128534 TI - A unifying model of the role of the infralimbic cortex in extinction and habits. AB - The infralimbic prefrontal cortex (IL) has been shown to be critical for the regulation of flexible behavior, but its precise function remains unclear. This region has been shown to be critical for the acquisition, consolidation, and expression of extinction learning, leading many to hypothesize that IL suppresses behavior as part of a "stop" network. However, this framework is at odds with IL function in habitual behavior in which the IL has been shown to be required for the expression and acquisition of ongoing habitual behavior. Here, we will review the current state of knowledge of IL anatomy and function in behavioral flexibility and provide a testable framework for a single IL mechanism underlying its function in both extinction and habit learning. PMID- 25128536 TI - Retrieval is not necessary to trigger reconsolidation of object recognition memory in the perirhinal cortex. AB - Memory retrieval has been considered as requisite to initiate memory reconsolidation; however, some studies indicate that blocking retrieval does not prevent memory from undergoing reconsolidation. Since N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the perirhinal cortex have been involved in object recognition memory formation, the present study evaluated whether retrieval and reconsolidation are independent processes by manipulating these glutamate receptors. The results showed that AMPA receptor antagonist infusions in the perirhinal cortex blocked retrieval, but did not affect memory reconsolidation, although NMDA receptor antagonist infusions disrupted reconsolidation even if retrieval was blocked. Importantly, neither of these antagonists disrupted short term memory. These data suggest that memory underwent reconsolidation even in the absence of retrieval. PMID- 25128538 TI - Exposure of airway smooth muscle cells to cigarette smoke extract. PMID- 25128539 TI - Response to letter by Dr. Marc Hershenson (exposure of airway smooth muscle cells to cigarette smoke extract). PMID- 25128544 TI - Ion chromatography for the precise analysis of chloride and sodium in sweat for the diagnosis of cystic fibrosis. AB - BACKGROUND: Measurement of chloride in sweat is an essential part of the diagnostic algorithm for cystic fibrosis. The lack in sensitivity and reproducibility of current methods led us to develop an ion chromatography/high performance liquid chromatography (IC/HPLC) method, suitable for the analysis of both chloride and sodium in small volumes of sweat. METHODS: Precision, linearity and limit of detection of an in-house developed IC/HPLC method were established. Method comparison between the newly developed IC/HPLC method and the traditional Chlorocounter was performed, and trueness was determined using Passing Bablok method comparison with external quality assurance material (Royal College of Pathologists of Australasia). RESULTS: Precision and linearity fulfill criteria as established by UK guidelines are comparable with inductively coupled plasma mass spectrometry methods. Passing Bablok analysis demonstrated excellent correlation between IC/HPLC measurements and external quality assessment target values, for both chloride and sodium. With a limit of quantitation of 0.95 mmol/L, our method is suitable for the analysis of small amounts of sweat and can thus be used in combination with the Macroduct collection system. CONCLUSIONS: Although a chromatographic application results in a somewhat more expensive test compared to a Chlorocounter test, more accurate measurements are achieved. In addition, simultaneous measurements of sodium concentrations will result in better detection of false positives, less test repeating and thus faster and more accurate and effective diagnosis. The described IC/HPLC method, therefore, provides a precise, relatively cheap and easy-to-handle application for the analysis of both chloride and sodium in sweat. PMID- 25128545 TI - David W. Talmage, M.D. (AAI '54) 1919-2014. PMID- 25128537 TI - 17beta-Estradiol regulates histone alterations associated with memory consolidation and increases Bdnf promoter acetylation in middle-aged female mice. AB - Histone acetylation is essential for hippocampal memory formation in young adult rodents. Although dysfunctional histone acetylation has been associated with age related memory decline in male rodents, little is known about whether histone acetylation is altered by aging in female rodents. In young female mice, the ability of 17beta-estradiol (E2) to enhance object recognition memory consolidation requires histone H3 acetylation in the dorsal hippocampus. However, the extent to which histone acetylation is regulated by E2 in middle-aged females is unknown. The mnemonic benefits of E2 in aging females appear to be greatest in middle age, and so pinpointing the molecular mechanisms through which E2 enhances memory at this age could lead to the development of safer and more effective treatments for maintaining memory function without the side effects of current therapies. Here, we show that dorsal hippocampal infusion of E2 rapidly enhanced object recognition and spatial memory, and increased histone H3 acetylation in the dorsal hippocampus, while also significantly reducing levels of histone deacetylase (HDAC2 and HDAC3) proteins. E2 specifically increased histone H3 acetylation at Bdnf promoters pII and pIV in the dorsal hippocampus of both young and middle-aged mice, despite age-related decreases in pI and pIV acetylation. Furthermore, levels of mature BDNF and pro-BDNF proteins in the dorsal hippocampus were increased by E2 in middle-aged females. Together, these data suggest that the middle-aged female dorsal hippocampus remains epigenetically responsive to E2, and that E2 may enhance memory in middle-aged females via epigenetic regulation of Bdnf. PMID- 25128546 TI - Comment on "aneurysmal lesions of patients with abdominal aortic aneurysm contain clonally expanded T cells". PMID- 25128547 TI - Response to comment on "aneurysmal lesions of patients with abdominal aortic aneurysm contain clonally expanded T cells". PMID- 25128548 TI - Just the FACS. PMID- 25128549 TI - Pillars article: cell sorting: automated separation of Mammalian cells as a function of intracellular fluorescence. Science. 1969. 166: 747-749. PMID- 25128550 TI - Pillars article: demonstration that antigen-binding cells are precursors of antibody-producing cells after purification with a fluorescence-activated cell sorter. Proc. Natl. Acad. Sci. 1972. 69: 1934-1938. PMID- 25128551 TI - Hematopoiesis in steady-state versus stress: self-renewal, lineage fate choice, and the conversion of danger signals into cytokine signals in hematopoietic stem cells. AB - Long-term hematopoietic stem cells (LT-HSCs) replenish the innate and adaptive immune compartments throughout life. Although significant progress has defined the major transcription factors that regulate lineage specification, the architectural proteins that globally coordinate DNA methylation, histone modification, and changes in gene expression are poorly defined. Provocative new studies establish the chromatin organizer special AT-rich binding protein 1 (Satb1) as one such global regulator in LT-HSCs. Satb1 is a nuclear organizer that partitions chromatin through the formation of cage-like structures. By integrating epigenetic and transcriptional pathways, Satb1 coordinates LT-HSC division, self-renewal, and lymphoid potential. Unexpected among the assortment of genes under Satb1 control in hematopoietic stem cells (HSCs) are cytokines, a finding that takes on additional importance with the provocative finding that short-term HSCs and downstream multipotent progenitors are potent and biologically relevant cytokine secretors during stress-mediated hematopoiesis. Together, these studies reveal a new mechanism of fate regulation and an unforeseen functional capability of HSCs. PMID- 25128557 TI - 'The battle for life': Pasteur, anthrax, and the first probiotics. PMID- 25128552 TI - The multifaceted roles of Bcl11b in thymic and peripheral T cells: impact on immune diseases. AB - The transcription factor Bcl11b is expressed in all T cell subsets and progenitors, starting from the DN2 stage of T cell development, and it regulates critical processes implicated in the development, function, and survival of many of these cells. Among the common roles of Bcl11b in T cell progenitors and mature T cell subsets are the repression of the innate genetic program and, to some extent, expression maintenance of TCR-signaling components. However, Bcl11b also has unique roles in specific T cell populations, suggesting that its functions depend on cell type and activation state of the cell. In this article, we provide a comprehensive review of the roles of Bcl11b in progenitors, effector T cells, regulatory T cells, and invariant NKT cells, as well as its impact on immune diseases. While emphasizing common themes, including some that might be extended to skin and neurons, we also describe the control of specific functions in different T cell subsets. PMID- 25128559 TI - Influence of optic flow on the control of heading and target egocentric direction during steering toward a goal. AB - Although previous studies have shown that people use both optic flow and target egocentric direction to walk or steer toward a goal, it remains in question how enriching the optic flow field affects the control of heading specified by optic flow and the control of target egocentric direction during goal-oriented locomotion. In the current study, we used a control-theoretic approach to separate the control response specific to these two cues in the visual control of steering toward a goal. The results showed that the addition of optic flow information (such as foreground motion and global flow) in the display improved the overall control precision, the amplitude, and the response delay of the control of heading. The amplitude and the response delay of the control of target egocentric direction were, however, not affected. The improvement in the control of heading with enriched optic flow displays was mirrored by an increase in the accuracy of heading perception. The findings provide direct support for the claim that people use the heading specified by optic flow as well as target egocentric direction to walk or steer toward a goal and suggest that the visual system does not internally weigh these two cues for goal-oriented locomotion control. PMID- 25128556 TI - Global mass spectrometry and transcriptomics array based drug profiling provides novel insight into glucosamine induced endoplasmic reticulum stress. AB - We investigated the molecular effects of glucosamine supplements, a popular and safe alternative to nonsteroidal anti-inflammatory drugs, for decreasing pain, inflammation, and maintaining healthy joints. Numerous studies have reported an array of molecular effects after glucosamine treatment. We questioned whether the differences in the effects observed in previous studies were associated with the focus on a specific subproteome or with the use of specific cell lines or tissues. To address this question, global mass spectrometry- and transcription array-based glucosamine drug profiling was performed on malignant cell lines from different stages of lymphocyte development. We combined global label-free MS based protein quantitation with an open search for modifications to obtain the best possible proteome coverage. Our data were largely consistent with previous studies in a variety of cellular models. We mainly observed glucosamine induced O GlcNAcylation/O-GalNAcylation (O-HexNAcylation); however, we also observed global and local changes in acetylation, methylation, and phosphorylation. For example, our data provides two additional examples of "yin-yang" between phosphorylation and O-HexNAcylation. Furthermore, we mapped novel O-HexNAc sites on GLU2B and calnexin. GLU2B and calnexin are known to be located in the endoplasmic reticulum (ER) and involved in protein folding and quality control. The O-HexNAc sites were regulated by glucosamine treatment and correlated with the up-regulation of the ER stress marker GRP78. The occupancy of O-HexNAc on GLU2B and calnexin sites differed between the cytosolic and nuclear fractions with a higher occupancy in the cytosolic fraction. Based on our data we propose the hypothesis that O-HexNAc either inactivates calnexin and/or targets it to the cytosolic fraction. Further, we hypothesize that O-HexNAcylation induced by glucosamine treatment enhances protein trafficking. PMID- 25128561 TI - Tetraspanins at a glance. AB - Tetraspanins are a family of proteins with four transmembrane domains that play a role in many aspects of cell biology and physiology; they are also used by several pathogens for infection and regulate cancer progression. Many tetraspanins associate specifically and directly with a limited number of proteins, and also with other tetraspanins, thereby generating a hierarchical network of interactions. Through these interactions, tetraspanins are believed to have a role in cell and membrane compartmentalization. In this Cell Science at a Glance article and the accompanying poster, we describe the basic principles underlying tetraspanin-based assemblies and highlight examples of how tetraspanins regulate the trafficking and function of their partner proteins that are required for the normal development and function of several organs, including, in humans, the eye, the kidney and the immune system. PMID- 25128560 TI - Response features across the auditory midbrain reveal an organization consistent with a dual lemniscal pathway. AB - The central auditory system has traditionally been divided into lemniscal and nonlemniscal pathways leading from the midbrain through the thalamus to the cortex. This view has served as an organizing principle for studying, modeling, and understanding the encoding of sound within the brain. However, there is evidence that the lemniscal pathway could be further divided into at least two subpathways, each potentially coding for sound in different ways. We investigated whether such an interpretation is supported by the spatial distribution of response features in the central nucleus of the inferior colliculus (ICC), the part of the auditory midbrain assigned to the lemniscal pathway. We recorded responses to pure tone stimuli in the ICC of ketamine-xylazine-anesthetized guinea pigs and used three-dimensional brain reconstruction techniques to map the location of the recording sites. Compared with neurons in caudal-and-medial regions within an isofrequency lamina of the ICC, neurons in rostral-and-lateral regions responded with shorter first-spike latencies with less spiking jitter, shorter durations of spiking responses, a higher proportion of spikes occurring near the onset of the stimulus, lower thresholds, and larger local field potentials with shorter latencies. Further analysis revealed two distinct clusters of response features located in either the caudal-and-medial or the rostral-and-lateral parts of the isofrequency laminae of the ICC. Thus we report substantial differences in coding properties in two regions of the ICC that are consistent with the hypothesis that the lemniscal pathway is made up of at least two distinct subpathways from the midbrain up to the cortex. PMID- 25128563 TI - Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the morphological polarization of developing neurons. AB - Final morphological polarization of neurons, with the development of a distinct axon and several dendrites, is preceded by phases where they have a non-polarized architecture. The earliest of these phases is that of the round neuron arising from the last mitosis. A second non-polarized stage corresponds to the bipolar neuron, with two morphologically identical neurites. Both phases have their distinctive relevance in the establishment of neuronal polarity. During the round cell stage, a decision is made as to where from the cell periphery a first neurite will form, thus creating the first sign of asymmetry. At the bipolar stage a decision is made as to which of the two neurites becomes the axon in neurons polarizing in vitro, and the leading edge in neurons in situ. In this study, we analysed cytoskeletal and membrane dynamics in cells at these two 'pre polarity' stages. By means of time lapse imaging in dissociated hippocampal neurons and ex vivo cortical slices, we show that both stages are characterized by polarized intracellular arrangements. However, the stages have distinct temporal hierarchies: polarized actin dynamics marks the site of first polarization in round cells, whereas polarized membrane dynamics precedes asymmetric growth in the bipolar stage. PMID- 25128562 TI - KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2. AB - Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma membrane trafficking are unknown. Here, we have identified a key role of the kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from the Golgi to the endothelial cell surface. KIF13B is shown to interact directly with VEGFR2 on microtubules. We also observed that overexpression of truncated versions of KIF13B containing the binding domains that interact with VEGFR2 inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGF mediated endothelial migration, capillary tube formation and neo-vascularization in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2 towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to the endothelial cell surface mediates angiogenesis. PMID- 25128564 TI - The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle. AB - The centrosome acts as the major microtubule-organizing center (MTOC) for cytoskeleton maintenance in interphase and mitotic spindle assembly in vertebrate cells. It duplicates only once per cell cycle in a highly spatiotemporally regulated manner. When the cell undergoes mitosis, the duplicated centrosomes separate to define spindle poles and monitor the assembly of the bipolar mitotic spindle for accurate chromosome separation and the maintenance of genomic stability. However, centrosome abnormalities occur frequently and often lead to monopolar or multipolar spindle formation, which results in chromosome instability and possibly tumorigenesis. A number of studies have begun to dissect the role of mitotic kinases, including NIMA-related kinases (Neks), cyclin dependent kinases (CDKs), Polo-like kinases (Plks) and Aurora kinases, in regulating centrosome duplication, separation and maturation and subsequent mitotic spindle assembly during cell cycle progression. In this Commentary, we review the recent research progress on how these mitotic kinases are coordinated to couple the centrosome cycle with the cell cycle, thus ensuring bipolar mitotic spindle fidelity. Understanding this process will help to delineate the relationship between centrosomal abnormalities and spindle defects. PMID- 25128566 TI - Quantifying mRNA targeting to P-bodies in living human cells reveals their dual role in mRNA decay and storage. AB - The 5'-to-3' mRNA degradation machinery localizes to cytoplasmic processing bodies (P-bodies), which are non-membranous structures found in all eukaryotes. Although P-body function has been intensively studied in yeast, less is known about their role in mammalian cells, such as whether P-body enzymes are actively engaged in mRNA degradation or whether P-bodies serve as mRNA storage depots, particularly during cellular stress. We examined the fate of mammalian mRNAs in P bodies during translational stress, and show that mRNAs accumulate within P bodies during amino acid starvation. The 5' and 3' ends of the transcripts residing in P-bodies could be identified, but poly(A) tails were not detected. Using the MS2 mRNA-tagging system for mRNA visualization in living cells, we found that a stationary mRNA population formed in P-bodies during translational stress, which cleared gradually after the stress was relieved. Dcp2-knockdown experiments showed that there is constant degradation of part of the P-body associated mRNA population. This analysis demonstrates the dual role of P-bodies as decay sites and storage areas under regular and stress conditions. PMID- 25128565 TI - Turning a new page on nucleostemin and self-renewal. AB - A quintessential trait of stem cells is embedded in their ability to self-renew without incurring DNA damage as a result of genome replication. One key self renewal factor is the nucleolar GTP-binding protein nucleostemin (also known as guanine-nucleotide-binding protein-like 3, GNL3, in invertebrate species). Several studies have recently pointed to an unexpected role of nucleostemin in safeguarding the genome integrity of stem and cancer cells. Since its discovery, the predominant presence of nucleostemin in the nucleolus has led to the notion that it might function in the card-carrying event of the nucleolus--the biogenesis of ribosomes. As tantalizing as this might be, a ribosomal role of nucleostemin is refuted by evidence from recent studies, which argues that nucleostemin depletion triggers a primary event of DNA damage in S phase cells that then leads to ribosomal perturbation. Furthermore, there have been conflicting reports regarding the p53 dependency of nucleostemin activity and the cell cycle arrest profile of nucleostemin-depleted cells. In this Commentary, I propose a model that explains how the many contradictory observations surrounding nucleostemin can be reconciled and suggest that this protein might not be as multi-tasking as has been previously perceived. The story of nucleostemin highlights the complexity of the underlying molecular events associated with the appearance of any cell biological phenotype and also signifies a new understanding of the genome maintenance program in stem cells. PMID- 25128567 TI - Histone acetylation in astrocytes suppresses GFAP and stimulates a reorganization of the intermediate filament network. AB - Glial fibrillary acidic protein (GFAP) is the main intermediate filament in astrocytes and is regulated by epigenetic mechanisms during development. We demonstrate that histone acetylation also controls GFAP expression in mature astrocytes. Inhibition of histone deacetylases (HDACs) with trichostatin A or sodium butyrate reduced GFAP expression in primary human astrocytes and astrocytoma cells. Because splicing occurs co-transcriptionally, we investigated whether histone acetylation changes the ratio between the canonical isoform GFAPalpha and the alternative GFAPdelta splice variant. We observed that decreased transcription of GFAP enhanced alternative isoform expression, as HDAC inhibition increased the GFAPdelta?GFAPalpha ratio. Expression of GFAPdelta was dependent on the presence and binding of splicing factors of the SR protein family. Inhibition of HDAC activity also resulted in aggregation of the GFAP network, reminiscent of our previous findings of a GFAPdelta-induced network collapse. Taken together, our data demonstrate that HDAC inhibition results in changes in transcription, splicing and organization of GFAP. These data imply that a tight regulation of histone acetylation in astrocytes is essential, because dysregulation of gene expression causes the aggregation of GFAP, a hallmark of human diseases like Alexander's disease. PMID- 25128568 TI - Thyroid hormone and the stunned myocardium. AB - Acute critically ill patients experience a rapid decline in plasma free thyroid hormone levels (free triiodothyronine (FT3) and free levothyroxine (FT4)), with a marked elevation of reverse T3, recognized as the euthyroid sick syndrome (ESS) or low-T3 syndrome. The ESS is also often associated with depressed myocardial function, sometimes referred to as the 'stunned myocardium'. Its clinical effects may vary from minimal hemodynamic impairment to cardiogenic shock. Medical management may range from aspirin alone to placement of a left ventricular assist device. With adequate supportive therapy, recovery usually occurs within days or weeks. The effect of T3/T4 therapy has been studied in three conditions in which the ESS and myocardial functional depression have been documented - i) transient regional myocardial ischemia and reperfusion, ii) transient global myocardial ischemia in patients undergoing cardiac surgery on cardiopulmonary bypass, and iii) transient inadequate global myocardial perfusion in brain-dead potential organ donors. Under all three conditions, myocardial ischemia leads to rapid loss of high-energy phosphates, accumulation of myocardial tissue lactate, and probably loss of homeostasis of cytosolic calcium, which may further increase cell injury. There is an inability to generate ATP through the Krebs cycle, which reduces the high-energy phosphate pool essential for all cell ATPases. Under all three conditions, following administration of T3/T4, the myocardial dysfunction was rapidly reversed. We, therefore, cautiously advocate the use of thyroid hormonal therapy to any patient with the ESS and/or a stunned myocardium. PMID- 25128569 TI - Local edge statistics provide information regarding occlusion and nonocclusion edges in natural scenes. AB - Edges in natural scenes can result from a number of different causes. In this study, we investigated the statistical differences between edges arising from occlusions and nonocclusions (reflectance differences, surface change, and cast shadows). In the first experiment, edges in natural scenes were identified using the Canny edge detection algorithm. Observers then classified these edges as either an occlusion edge (one region of an image occluding another) or a nonocclusion edge. The nonocclusion edges were further subclassified as due to a reflectance difference, a surface change, or a cast shadow. We found that edges were equally likely to be classified as occlusion or nonocclusion edges. Of the nonocclusion edges, approximately 33% were classified as reflectance changes, 9% as cast shadows, and 58% as surface changes. We also analyzed local statistical properties like contrast, average edge profile, and slope of the edges. We found significant differences between the contrast values for each category. Based on the local contrast statistics, we developed a maximum likelihood classifier to label occlusion and nonocclusion edges. An 80%-20% cross validation demonstrated that the human classification could be predicted with 83% accuracy. Overall, our results suggest that for many edges in natural scenes, there exists local statistical information regarding the cause of the edge. We believe that this information can potentially be used by the early visual system to begin the process of segregating objects from their backgrounds. PMID- 25128571 TI - Different fixational eye movements mediate the prevention and the reversal of visual fading. AB - Fixational eye movements (FEMs; including microsaccades, drift and tremor) are thought to improve visibility during fixation by thwarting neural adaptation to unchanging stimuli, but how the different FEM types influence this process is a matter of debate. Attempts to answer this question have been hampered by the failure to distinguish between the prevention of fading (where fading is blocked before it happens in the first place) and the reversal of fading (where vision is restored after fading has already occurred). Because fading during fixation is a detriment to clear vision, the prevention of fading, which avoids visual degradation before it happens, is a more desirable scenario than improving visibility after fading has occurred. Yet previous studies have not examined the role of FEMs in the prevention of fading, but have focused on visual restoration instead. Here we set out to determine the differential contributions and efficacies of microsaccades and drift to preventing fading in human vision. Our results indicate that both microsaccades and drift mediate the prevention of visual fading. We also found that drift is a potentially larger contributor to preventing fading than microsaccades, although microsaccades are more effective than drift. Microsaccades moreover prevented foveal and peripheral fading in an equivalent fashion, and their efficacy was independent of their size, number, and direction. Our data also suggest that faster drift may prevent fading better than slower drift. These findings may help to reconcile the long-standing controversy concerning the comparative roles of microsaccades and drift in visibility during fixation. PMID- 25128570 TI - Plasticity in the brainstem vagal circuits controlling gastric motor function triggered by corticotropin releasing factor. AB - Stress impairs gastric emptying, reduces stomach compliance and induces early satiety via vagal actions. We have shown recently that the ability of the anti stress neuropeptide oxytocin (OXT) to modulate vagal brainstem circuits undergoes short-term plasticity via alterations in cAMP levels subsequent to vagal afferent fibre-dependent activation of metabotropic glutamate receptors. The aim of the present study was to test the hypothesis that the OXT-induced gastric response undergoes plastic changes in the presence of the prototypical stress hormone, corticotropin releasing factor (CRF). Whole cell patch clamp recordings showed that CRF increased inhibitory GABAergic synaptic transmission to identified corpus-projecting dorsal motor nucleus of the vagus (DMV) neurones. In naive brainstem slices, OXT perfusion had no effect on inhibitory synaptic transmission; following exposure to CRF (and recovery from its actions), however, re-application of OXT inhibited GABAergic transmission in the majority of neurones tested. This uncovering of the OXT response was antagonized by pretreatment with protein kinase A or adenylate cyclase inhibitors, H89 and di deoxyadenosine, respectively, indicating a cAMP-mediated mechanism. In naive animals, OXT microinjection in the dorsal vagal complex induced a NO-mediated corpus relaxation. Following CRF pretreatment, however, microinjection of OXT attenuated or, at times reversed, the gastric relaxation which was insensitive to l-NAME but was antagonized by pretreatment with a VIP antagonist. Immunohistochemical analyses of vagal motoneurones showed an increased number of oxytocin receptors present on GABAergic terminals of CRF-treated or stressed vs. naive rats. These results indicate that CRF alters vagal inhibitory circuits that uncover the ability of OXT to modulate GABAergic currents and modifies the gastric corpus motility response to OXT. PMID- 25128573 TI - Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials. AB - Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl(-) and KATP K(+) ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (lambda) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and lambda as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ~3-fold, fully reversible increase in Gm after the firing of 1450 1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above -20 mV. PMID- 25128575 TI - Catecholamine exocytosis during low frequency stimulation in mouse adrenal chromaffin cells is primarily asynchronous and controlled by the novel mechanism of Ca2+ syntilla suppression. AB - Adrenal chromaffin cells (ACCs), stimulated by the splanchnic nerve, generate action potentials (APs) at a frequency near 0.5 Hz in the resting physiological state, at times described as 'rest and digest'. How such low frequency stimulation in turn elicits sufficient catecholamine exocytosis to set basal sympathetic tone is not readily explained by the classical mechanism of stimulus secretion coupling, where exocytosis is synchronized to AP-induced Ca(2+) influx. By using simulated action potentials (sAPs) at 0.5 Hz in isolated patch-clamped mouse ACCs, we show here that less than 10% of all catecholaminergic exocytosis, measured by carbon fibre amperometry, is synchronized to an AP. The asynchronous phase, the dominant phase, of exocytosis does not require Ca(2+) influx. Furthermore, increased asynchronous exocytosis is accompanied by an AP-dependent decrease in frequency of Ca(2+) syntillas (i.e. transient, focal Ca(2+) release from internal stores) and is ryanodine sensitive. We propose a mechanism of disinhibition, wherein APs suppress Ca(2+) syntillas, which themselves inhibit exocytosis as they do in the case of spontaneous catecholaminergic exocytosis. PMID- 25128574 TI - PGC1-alpha over-expression prevents metabolic alterations and soleus muscle atrophy in hindlimb unloaded mice. AB - Prolonged skeletal muscle inactivity causes muscle fibre atrophy. Redox imbalance has been considered one of the major triggers of skeletal muscle disuse atrophy, but whether redox imbalance is actually the major cause or simply a consequence of muscle disuse remains of debate. Here we hypothesized that a metabolic stress mediated by PGC-1alpha down-regulation plays a major role in disuse atrophy. First we studied the adaptations of soleus to mice hindlimb unloading (HU) in the early phase of disuse (3 and 7 days of HU) with and without antioxidant treatment (trolox). HU caused a reduction in cross-sectional area, redox status alteration (NRF2, SOD1 and catalase up-regulation), and induction of the ubiquitin proteasome system (MuRF-1 and atrogin-1 mRNA up-regulation) and autophagy (Beclin1 and p62 mRNA up-regulation). Trolox completely prevented the induction of NRF2, SOD1 and catalase mRNAs, but not atrophy or induction of catabolic systems in unloaded muscles, suggesting that oxidative stress is not a major cause of disuse atrophy. HU mice showed a marked alteration of oxidative metabolism. PGC-1alpha and mitochondrial complexes were down-regulated and DRP1 was up-regulated. To define the link between mitochondrial dysfunction and disuse muscle atrophy we unloaded mice overexpressing PGC-1alpha. Transgenic PGC-1alpha animals did not show metabolic alteration during unloading, preserving muscle size through the reduction of autophagy and proteasome degradation. Our results indicate that mitochondrial dysfunction plays a major role in disuse atrophy and that compounds inducing PGC-1alpha expression could be useful to treat/prevent muscle atrophy. PMID- 25128577 TI - Mentoring practices benefiting pediatric nurses. AB - Previous studies examining predictors of pediatric nurse protege mentoring benefits demonstrated that protege perception of quality was the single best predictor of mentoring benefits. The ability to identify the mentoring practices that predict specific benefits for individual nurses provides a better understanding of how mentoring relationships can be leveraged within health care organizations promoting mutual mentoring benefits. This descriptive correlational, non-experimental study of nurses at a northeast Ohio, Magnet(r) recognized, free-standing pediatric hospital advances nursing science by demonstrating how mentoring practices benefit pediatric nurse proteges. PMID- 25128576 TI - Activation of TRPC channels contributes to OA-NO2-induced responses in guinea-pig dorsal root ganglion neurons. AB - Effects of nitro-oleic acid (OA-NO2) on TRP channels were examined in guinea-pig dissociated dorsal root ganglia (DRG) neurons using calcium imaging and patch clamp techniques. OA-NO2 increased intracellular Ca(2+) in 60-80% DRG neurons. 1 Oleoyl-2acetyl-sn-glycerol (OAG), a TRPC agonist, elicited responses in 36% of OA NO2-sensitive neurons while capsaicin (TRPV1 agonist) or allyl-isothiocyanate (AITC, TRPA1 agonist) elicited responses in only 16% and 10%, respectively, of these neurons. A TRPV1 antagonist (diarylpiperazine, 5 MUm) in combination with a TRPA1 antagonist (HC-030031, 30 MUm) did not change the amplitude of the Ca(2+) transients or percentage of neurons responding to OA-NO2; however, a reducing agent DTT (50 mm) or La(3+) (50 MUm) completely abolished OA-NO2 responses. OA NO2 also induced a transient inward current associated with a membrane depolarization followed by a prolonged outward current and hyperpolarization in 80% of neurons. The reversal potentials of inward and outward currents were approximately -20 mV and -60 mV, respectively. Inward current was reduced when extracellular Na(+) was absent, but unchanged by niflumic acid (100 MUm), a Cl(-) channel blocker. Outward current was abolished in the absence of extracellular Ca(2+) or a combination of two Ca(2+)-activated K(+) channel blockers (iberiotoxin, 100 nm and apamin, 1 MUm). BTP2 (1 or 10 MUm), a broad spectrum TRPC antagonist, or La(3+) (50 MUm) completely abolished OA-NO2 currents. RT-PCR performed on mRNA extracted from DRGs revealed the expression of all seven subtypes of TRPC channels. These results support the hypothesis that OA-NO2 activates TRPC channels other than the TRPV1 and TRPA1 channels already known to be targets in rat and mouse sensory neurons and challenge the prevailing view that electrophilic compounds act specifically on TRPA1 or TRPV1 channels. The modulation of sensory neuron excitability via actions on multiple TRP channels can contribute to the anti-inflammatory effect of OA-NO2. PMID- 25128578 TI - Enhanced survival of retinal ganglion cells is mediated by Muller glial cell derived PEDF. AB - The death of retinal ganglion cells (RGC) leads to visual impairment and blindness in ocular neurodegenerative diseases, primarily in glaucoma and diabetic retinopathy; hence, mechanisms that contribute to protecting RGC from ischemia/hypoxia are of great interest. We here address the role of retinal glial (Muller) cells and of pigment-epithelium-derived factor (PEDF), one of the main neuroprotectants released from the glial cells. We show that the hypoxia-induced loss in the viability of cultured purified RGC is due to apoptosis, but that the number of viable RGC increases when co-cultured with Muller glial cells suggesting that glial soluble mediators attenuate the death of RGC. When PEDF was ablated from Muller cells a significantly lower number of RGC survived in RGC Muller cell co-cultures indicating that PEDF is a major survival factor allowing RGC to escape cell death. We further found that RGC express a PEDF receptor known as patatin-like phospholipase domain-containing protein 2 (PNPLA2) and that PEDF exposure, as well as the presence of Muller cells, leads to an activation of nuclear factor (NF)-kappaB in RGC. Furthermore, adding an NF-kappaB inhibitor (SN50) to PEDF-treated RGC cultures reduced the survival of RGC. These findings strongly suggest that NF-kappaB activation in RGC is critically involved in the pro-survival action of Muller-cell derived PEDF and plays an important role in maintaining neuronal survival. PMID- 25128580 TI - Editorial. PMID- 25128579 TI - Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells. AB - The bulk of aqueous humor passing through the conventional outflow pathway must cross the inner wall endothelium of Schlemm's canal (SC), likely through micron sized transendothelial pores. SC pore density is reduced in glaucoma, possibly contributing to obstructed aqueous humor outflow and elevated intraocular pressure (IOP). Little is known about the mechanisms of pore formation; however, pores are often observed near dome-like cellular outpouchings known as giant vacuoles (GVs) where significant biomechanical strain acts on SC cells. We hypothesize that biomechanical strain triggers pore formation in SC cells. To test this hypothesis, primary human SC cells were isolated from three non glaucomatous donors (aged 34, 44 and 68), and seeded on collagen-coated elastic membranes held within a membrane stretching device. Membranes were then exposed to 0%, 10% or 20% equibiaxial strain, and the cells were aldehyde-fixed 5 min after the onset of strain. Each membrane contained 3-4 separate monolayers of SC cells as replicates (N = 34 total monolayers), and pores were assessed by scanning electron microscopy in 12 randomly selected regions (~65,000 MUm(2) per monolayer). Pores were identified and counted by four independent masked observers. Pore density increased with strain in all three cell lines (p < 0.010), increasing from 87 +/- 36 pores/mm(2) at 0% strain to 342 +/- 71 at 10% strain; two of the three cell lines showed no additional increase in pore density beyond 10% strain. Transcellular "I-pores" and paracellular "B-pores" both increased with strain (p < 0.038), however B-pores represented the majority (76%) of pores. Pore diameter, in contrast, appeared unaffected by strain (p = 0.25), having a mean diameter of 0.40 MUm for I-pores (N = 79 pores) and 0.67 MUm for B pores (N = 350 pores). Pore formation appears to be a mechanosensitive process that is triggered by biomechanical strain, suggesting that SC cells have the ability to modulate local pore density and filtration characteristics of the inner wall endothelium based on local biomechanical cues. The molecular mechanisms of pore formation and how they become altered in glaucoma may be studied in vitro using stretched SC cells. PMID- 25128581 TI - Roles of the two type II NADH dehydrogenases in the survival of Mycobacterium tuberculosis in vitro. AB - Most bacteria are able to generate sufficient amounts of ATP from substrate level phosphorylation, thus rendering the respiratory oxidative phosphorylation non critical. In mycobacteria, including Mycobacterium tuberculosis, ATP generation by oxidative phosphorylation is an essential process. Of the two types of NADH dehydrogenases (type I and type II), the type II NADH dehydrogenase (Ndh) which is inhibited by phenothiazines has been thought to be essential. In M. tuberculosis there are two Ndh isozymes (Ndh and NdhA) coded by ndh and ndhA genes respectively. Ndh and NdhA share a high degree of amino acid similarity. Both the enzymes have been shown to be enzymatically active and are inhibited by phenothiazines, suggesting a functional similarity between the two. We attempted gene knockout of ndh and ndhA genes in wild type and merodiploid backgrounds. It was found that ndh gene cannot be inactivated in a wild type background, though it was possible to do so when an additional copy of ndh was provided. This showed that in spite of its apparent functional equivalence, NdhA cannot complement the loss of Ndh in M. tuberculosis. We also showed that NdhA is not essential in M. tuberculosis as the ndhA gene could be deleted in a wild type strain of M. tuberculosis without causing any adverse effects in vitro. RT-PCR analysis of in vitro grown M. tuberculosis showed that ndhA gene is actively transcribed. This study suggests that despite being biochemically similar, Ndh and NdhA play different roles in the physiology of M. tuberculosis. PMID- 25128582 TI - Isolation, characterization and expression analysis of the BABY BOOM (BBM) gene from Larix kaempferi * L. olgensis during adventitious rooting. AB - The full-length cDNA and genomic sequences of the BABY BOOM (BBM) gene, designated LkBBM, were isolated from Larix kaempferi * Larix olgensis. The 3324 bp cDNA was cloned and its open reading frame (ORF) consists of 2370 nucleotides. The deduced 789 amino acid protein contains two AP2 domains and a BBM specific motif. Four conserved motifs between BBM and PLT were identified, which may be conducive to the similar function of BBM and PLT. The three dimensional (3D) structure of LkBBM was predicted and beta-sheets in the AP2-R2 domain of LkBBM might recognize the specific base pairs in the major groove. Analysis of the LkBBM gene structure indicates that the gene has eight introns and nine exons. In the 5'-flanking promoter region of LkBBM, many important potential cis-acting elements were identified, such as the TATABOX5 element (a functional TATA element), ROOTMOTIFTAPOX1 element (element of root specificity), AUXREPSIAA4 element (element involved in auxin responsiveness and gene expression in root meristem), MYB1AT element (element involved in MYB recognition), ARR1AT element (element involved in cytokinin responsiveness), GARE1OSREP1 element (element involved in gibberellin responsiveness) and PYRIMIDINEBOXHVEPB1 element (element involved in abscisic acid responsiveness), which all suggested that the expression of LkBBM is highly regulated. Compared with gene expression levels in the stem, stem tip and leaf, LkBBM shows a specific expression in the root, which indicates that LkBBM plays a key role in regulating the development and growth of root in larch. In the processing of larch adventitious root formation, LkBBM started to express on the eighth day after rooting treatment and its transcript level increased continuously afterwards. According to the gene characteristics, LkBBM is proposed as a molecular marker for root primordia of larch, and the initial period of LkBBM expression may be the formation period of root primordia in the processing of adventitious rooting of larch. PMID- 25128583 TI - Association of TLR and TREM-1 gene polymorphisms with risk of coronary artery disease in a Russian population. AB - Atherosclerosis, manifesting itself as acute coronary syndrome, stroke, and peripheral arterial diseases, is a chronic progressive inflammatory disease which is driven by responses of both innate and adaptive immunity. Toll-like receptors (TLRs) and Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) are important effectors of the innate immune system, and polymorphisms within genes encoding them may increase risk of occurrence of various pathologies including cardiovascular disorders. Thus, we carried out a genetic association study on the sample of 702 consecutive Caucasian (Russian) patients with coronary artery disease (CAD) and 300 age-, sex-, and ethnicity-matched healthy controls. We revealed that the C/C genotype of the TLR1 rs5743551 polymorphism was significantly associated with a reduced risk of CAD according to the recessive model (OR=0.41, 95% CI=0.20-0.84, P=0.017, adjusted by age and gender). Concerning TREM-1 gene polymorphisms, we found that A/A genotype of the rs2234237 polymorphism, the G/G genotype of the rs6910730 polymorphism, the C/C genotype of the rs9471535 polymorphism, and the T/T genotype of the rs4711668 polymorphism were significantly associated with elevated CAD risk according to the recessive model (OR=5.52, 95% CI=1.17-25.98, P=0.011; OR=4.28, 95% CI=1.09-16.81, P=0.021; OR=5.55, 95% CI=1.18-26.09, P=0.011, and OR=1.66, 95% CI=1.10-2.52, P=0.014, respectively, adjusted by age and gender). Conversely, the G allele of the rs1817537 polymorphism, the T allele of the rs2234246 polymorphism, and the T allele of the rs3804277 polymorphism significantly correlated with similarly decreased risk of CAD according to the dominant model (OR=0.57, 95% CI=0.40-0.81, P=0.0013; OR=0.59, 95% CI=0.42-0.84, P=0.003, and OR=0.58, 95% CI=0.41-0.81, P=0.0014, respectively, adjusted by age and gender). We conclude that certain TLR and TREM-1 gene polymorphisms may be associated with CAD in Russian population; however, their significance as predictive and pathogenic markers of CAD should be interpreted with caution in other populations. PMID- 25128584 TI - PDE7A1 hydrolyzes cCMP. AB - The degradation and biological role of the cyclic pyrimidine nucleotide cCMP is largely elusive. We investigated nucleoside 3',5'-cyclic monophosphate (cNMP) specificity of six different recombinant phosphodiesterases (PDEs) by using a highly-sensitive HPLC-MS/MS detection method. PDE7A1 was the only enzyme that hydrolyzed significant amounts of cCMP. Enzyme kinetic studies using purified GST tagged truncated PDE7A1 revealed a cCMP KM value of 135 +/- 19 MUM. The Vmax for cCMP hydrolysis reached 745 +/- 27 nmol/(minmg), which is about 6-fold higher than the corresponding velocity for adenosine 3',5'-cyclic monophosphate (cAMP) degradation. In summary, PDE7A is a high-speed and low-affinity PDE for cCMP. PMID- 25128585 TI - Ins-4 and daf-28 function redundantly to regulate C. elegans L1 arrest. AB - Caenorhabditis elegans larvae reversibly arrest development in the first larval stage in response to starvation (L1 arrest or L1 diapause). Insulin-like signaling is a critical regulator of L1 arrest. However, the C. elegans genome encodes 40 insulin-like peptides, and it is unknown which peptides participate in nutritional control of L1 development. Work in other contexts has revealed that insulin-like genes can promote development ("agonists") or developmental arrest ("antagonists"), suggesting that such agonists promote L1 development in response to feeding. We measured mRNA expression dynamics with high temporal resolution for all 40 insulin-like genes during entry into and recovery from L1 arrest. Nutrient availability influences expression of the majority of insulin-like genes, with variable dynamics suggesting complex regulation. We identified thirteen candidate agonists and eight candidate antagonists based on expression in response to nutrient availability. We selected ten candidate agonists (daf-28, ins-3, ins-4, ins-5, ins-6, ins-7, ins-9, ins-26, ins-33 and ins-35) for further characterization in L1 stage larvae. We used destabilized reporter genes to determine spatial expression patterns. Expression of candidate agonists is largely overlapping in L1 stage larvae, suggesting a role of the intestine, chemosensory neurons ASI and ASJ, and the interneuron PVT in control of L1 development. Transcriptional regulation of candidate agonists is most significant in the intestine, as if internal nutrient status is a more important influence on transcription than sensory perception. Phenotypic analysis of single and compound deletion mutants did not reveal effects on L1 developmental dynamics, though simultaneous disruption of ins-4 and daf-28 increases survival of L1 arrest. Furthermore, overexpression of ins-4, ins-6 or daf-28 alone decreases survival and promotes cell division during starvation. These results suggest extensive functional overlap among insulin-like genes in nutritional control of L1 development while highlighting the role of ins-4, daf-28 and to a lesser extent ins-6. PMID- 25128587 TI - The neural correlates of tic inhibition in Gilles de la Tourette syndrome. AB - Tics in Gilles de la Tourette syndrome (GTS) resemble fragments of normal motor behaviour but appear in an intrusive, repetitive and context-inappropriate manner. Although tics can be voluntarily inhibited on demand, the neural correlates of this process remain unclear. 14 GTS adults without relevant comorbidities participated in this study. First, tic severity and voluntary tic inhibitory capacity were evaluated outside the scanner. Second, patients were examined with resting state functional magnetic resonance imaging (RS-fMRI) in two states, free ticcing and voluntary tic inhibition. Local synchronization of spontaneous fMRI-signal was analysed with regional homogeneity (ReHo) and differences between both states (free ticcing1000 mg L(-1). Inhibition of bioluminescence was generally a more sensitive endpoint for MTBE toxicity than measuring intracellular ATP levels and heterotrophic CO2 assimilation. A weak estrogenic response was detected for MTBE at concentrations ? 3.7 g L(-1) using an estrogen inducible bioluminescent yeast strain (S. cerevisiae BLYES). Microbial hydrolytic enzyme activity in groundwater was affected by MTBE with EC10 values of 0.5-787 mg L(-1), and EC50 values of 59 3073 for alkaline phosphatase, arylsulfatase, beta-1,4-glucanase, N-acetyl-beta-d glucosaminidase, and leucine-aminopeptidase. Microbial alkaline phosphatase and beta-1,4-glucanase activity were most sensitive to MTBE exposure with EC50 ? 64.8 mg L(-1). The study suggests that bioassays with luminescent A. fischeri, and fluorescent assays targeting hydrolytic enzyme activity are good candidates for monitoring microbial MTBE toxicity in contaminated water. PMID- 25128635 TI - Characteristics of online compulsive buying in Parisian students. AB - BACKGROUND: Online compulsive buying is a little-studied behavioral disorder. AIMS: To better understand its clinical aspects by focusing on (i) prevalence rate, (ii) correlation with other addictions, (iii) influence of means of access, (iv) motivations to shop to the internet and (v) financial and time-consuming consequences. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 200 students in two different centers of Paris Diderot University - Paris VII. MEASUREMENTS: Brief self-questionnaires, to screen online compulsive buying, internet addiction, alcohol and tobacco use disorders, to rate frequency of online purchase by private-sale websites, by advertising banners, by mobile phone or to avoid stores, to rate motivations like "more discreet", "lonelier", "larger variety of products", "more immediate positive feelings", and "cheaper" and to assess the largest amount of online purchasing and the average proportion of monthly earnings, and time spent, both day and night. FINDINGS: Prevalence of online compulsive buying was 16.0%, while prevalence of internet addiction was 26.0%. We found no significant relationship with cyberdependence, alcohol or tobacco use disorders. Online compulsive buyers accessed more often shopping online by private-sale websites (56.2% vs 30.5%, p<0.0001) or by mobile phone (22.5% vs 7.9%, p=0.005) and preferred online shopping because of exhaustive offer (p<0.0001) and immediate positive feelings (p<0.0001). Online compulsive buyers spent significantly more money and more time in online shopping. CONCLUSION: Online compulsive buying seems to be a distinctive behavioral disorder with specific factors of loss of control and motivations, and overall financial and time-consuming impacts. More research is needed to better characterize it. PMID- 25128636 TI - Indirect effects of smoking motives on adolescent anger dysregulation and smoking. AB - Cigarette smoking is one of the leading causes of disease and death in the United States, and smoking typically begins in adolescence. It is therefore important to understand factors that relate to increased risk for cigarette smoking during this stage of development. Adolescence is a period when emotion regulatory capacities are still emerging and a common affective state to be regulated is anger, which adult research has linked to nicotine use. Drawing from work suggesting that negative affect reduction motives are one of the most common reasons for cigarette smoking, the current study was designed to evaluate the indirect effects of negative affect reduction motives on the relation between anger dysregulation and nicotine use within a sample of 119 treatment-seeking adolescents enrolled in group-based residential therapy. Results were generally consistent with hypotheses, suggesting significant indirect effects of negative affect reduction smoking motives on the relation between anger dysregulation and smoking outcomes. Findings are discussed in terms of negative affect reduction motives for cigarette use in the context of anger regulation among youths. PMID- 25128637 TI - Technology-based support via telephone or web: a systematic review of the effects on smoking, alcohol use and gambling. AB - A systematic review of the literature on telephone or internet-based support for smoking, alcohol use or gambling was performed. Studies were included if they met the following criteria: The design being a randomized control trail (RCT), focused on effects of telephone or web based interventions, focused on pure telephone or internet-based self-help, provided information on alcohol or tobacco consumption, or gambling behavior, as an outcome, had a follow-up period of at least 3months, and included adults. Seventy-four relevant studies were found; 36 addressed the effect of internet interventions on alcohol consumption, 21 on smoking and 1 on gambling, 12 the effect of helplines on smoking, 2 on alcohol consumption, and 2 on gambling. Telephone helplines can have an effect on tobacco smoking, but there is no evidence of the effects for alcohol use or gambling. There are some positive findings regarding internet-based support for heavy alcohol use among U.S. college students. However, evidence on the effects of internet-based support for smoking, alcohol use or gambling are to a large extent inconsistent. PMID- 25128639 TI - Mass gathering medicine: 2014 Hajj and Umra preparation as a leading example. AB - The importation of infectious diseases during a mass gathering may result in outbreaks. Infectious diseases associated with mass gatherings vary depending on the type and location of the mass gathering. The annual Hajj to Makkah in Saudi Arabia is one of the largest annual religious mass gatherings in the world. Preparation for the Hajj encompasses multiple sectors to develop comprehensive plans. These plans include risk assessment, utilizing existing medical infrastructure, developing electronic and paper-based surveillance activity, and the use of information technology. In this review, we describe key features of the preparedness for the 2014 Hajj and Umra, review the recent impact of emerging viruses such as Ebola in West Africa and the Middle East respiratory syndrome coronavirus (MERS-CoV) in affected countries, and highlight the updated requirements and the required vaccines. PMID- 25128638 TI - A comparison of Cambodian-American adolescent substance use behavior to national and local norms. AB - INTRODUCTION: This study was designed to compare rates of alcohol, marijuana, and cigarette use in Cambodian-American adolescents with norms from nationally- and regionally-representative peers. METHODS: Substance use data from 439 10th grade Cambodian-American adolescents in Long Beach, California were compared to grade- and gender-matched nationally representative data from the Monitoring the Future study and data from the California Healthy Kids Survey of students within the same school district. RESULTS: Overall, the Cambodian-American youth were less likely than nationally- and regionally-representative youth to use alcohol, marijuana, and cigarettes. Specifically, relative to estimates obtained for the general population and students attending school in the same school district, Cambodian-American youth were significantly less likely to use alcohol and marijuana. Cambodian-American youth were also less likely than youth in the general population to smoke cigarettes, but did not differ statistically from youth within their same school district. CONCLUSIONS: As a group, Cambodian American youth may not be at especially high risk for substance use. As is the case with virtually all populations, some individuals within the Cambodian American group are likely to have more difficulty than others with substance use concerns. Thus, additional research is needed to identify factors that might help to identify high users with potential service needs. PMID- 25128640 TI - Lubricating recovery of damaged pleural mesothelium: effect of time and of phosphatidylcholines. AB - Effect of time and phosphatidylcholines (PCs) on lubrication of damaged mesothelium has been investigated. Marked increase in coefficient of kinetic friction (MU) of pleural specimens after mesothelial blotting and rewetting decreased by 23.4+/-3.5%, 41.8+/-3.8%, and 40.5+/-2.7% after 30min, 1h, and 2h. Hence, damaged mesothelium is able to partially reset lubricating molecules on its surface. Increase in MU of post-blotting Ringer 2h after addition of unsaturated PCs (3mg/ml) decreased a little more than after 2h Ringer. Effects of unsaturated and saturated PCs were similar, contrary to expectation raised by their different percentage in pleural and alveolar lavage. Effect of PCs did not increase at 6mg/ml, and was nil at 0.4mg/ml. Increase of MU after short phospholipase treatment decreased by 45.9+/-2.0% after 2h Ringer, and a little more after addition of unsaturated or saturated PCs. Hence, PCs, as other phospholipids, have a small effect, likely because of difficulty in resetting their relationships with main lubricating molecules. PMID- 25128641 TI - Influence of lung volume, fluid and capillary recruitment during positional changes and exercise on thoracic impedance in heart failure. AB - It is unclear how dynamic changes in pulmonary-capillary blood volume (Vc), alveolar lung volume (derived from end-inspiratory lung volume, EILV) and interstitial fluid (ratio of alveolar capillary membrane conductance and pulmonary capillary blood volume, Dm/Vc) influence lung impedance (Z(T)). The purpose of this study was to investigate if positional change and exercise result in increased EILV, Vc and/or lung interstitial fluid, and if Z(T) tracks these variables. METHODS: 12 heart failure (HF) patients underwent measurements (Z(T), EILV, Vc/Dm) at rest in the upright and supine positions, during exercise and into recovery. Inspiratory capacity was obtained to provide consistent measures of EILV while assessing Z(T). RESULTS: Z(T) increased with lung volume during slow vital capacity maneuvers (p<0.05). Positional change (upright->supine) resulted in an increased Z(T) (p<0.01), while Vc increased and EILV and Dm/Vc decreased (p<0.05). Moreover, during exercise Vc and EILV increased and Dm/Vc decreased (p<0.05), whereas, Z(T) did not change significantly (p>0.05). CONCLUSION: Impedance appears sensitive to changes in lung volume and body position which appear to generally overwhelm small acute changes in lung fluid when assed dynamically at rest or during exercise. PMID- 25128642 TI - The effect of chronic low back pain on tactile suppression during back movements. AB - The aim of the present study was to examine whether tactile suppression, the phenomenon whereby tactile perception is suppressed during movement, would occur in the context of back movements. Of particular interest, it was investigated if tactile suppression in the back would be attenuated in those suffering from chronic low back pain. Individuals with chronic low back pain (N = 30) and a matched control group (N = 24) detected tactile stimuli on three possible locations (back, arm, chest) while performing a back or arm movement, or no movement. We hypothesized that the movements would induce tactile suppression, and that this effect would be largest for low-intense stimuli on the moving body part. We further hypothesized that, during back movements, tactile suppression on the back would be less pronounced in the chronic low back pain group than in the control group. The results showed the expected general tactile suppression effects. The hypothesis of back-specific attenuation of tactile suppression in the chronic low back pain group was not supported. However, back-specific tactile suppression in the chronic low back pain group was less pronounced in those who performed the back movements more slowly. PMID- 25128643 TI - Application of a liquid chromatography-tandem mass spectrometry method to the pharmacokinetics, tissue distribution and excretion studies of sweroside in rats. AB - A sensitive, reliable and accurate high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) was developed and validated for the quantification of sweroside in rat plasma, tissue and excretion. A single-step protein precipitation by methanol was used to prepare samples. Sweroside and swertiamarin (internal standard, IS) were separated by using a C18 column and a mobile phase consisted of methanol and water containing 0.1% formic acid running at a flow rate of 0.8ml/min for 6min. Detection and quantification were performed using a mass spectrometer by the multiple-reaction monitoring (MRM) in positive electrospray ionization mode. The optimized mass transition ion pairs (m/z) for quantitation were [M+H](+)359.1->197.2 for sweroside and [M+Na](+)397.4->165.3 for swertiamarin (IS), respectively. The inter-day precision (RSD %) was less than 11.20% and intra-day precision (RSD %) was less than 10.90%, while the inter day accuracy (RE %) was ranged from -9.69 to 9.17% and intra-day accuracy (RE %) was ranged from -10.56 to 13.47%. The mean elimination half-life (t1/2) of sweroside for 5, 10 and 15mg/kg dose were 78.8, 67.6 and 77.2min, respectively. And sweroside follows linear plasma pharmacokinetics across the investigated dosage range in rats (5-15mg/kg). The absolute bioavailability (F %) of sweroside was 11.90% on average. The results of tissue distribution showed the higher sweroside concentrations were found in kidney, liver, spleen and lung, and the small amount of drug was distributed into the brain tissue. The high distribution in liver confirms the reports that sweroside has hepatoprotective activity and promoted liver regeneration, and there was no long-term accumulation of sweroside in rat tissues. Total recoveries of sweroside within 48h were 0.67% in bile, 1.55% in urine and 0.46% in feces, which might be resulted from liver first-pass effect. The above results suggested that sweroside was mainly excreted as the metabolites. PMID- 25128644 TI - Trace elements in major marketed marine bivalves from six northern coastal cities of China: concentrations and risk assessment for human health. AB - One hundred and fifty nine samples of nine edible bivalve species (Argopecten irradians, Chlamys farreri, Crassostrea virginica, Lasaea nipponica, Meretrix meretrix, Mytilus edulis, Ruditapes philippinarum, Scapharca subcrenata and Sinonovacula constricta) were randomly collected from eight local seafood markets in six big cities (Dalian, Qingdao, Rizhao, Weifang, Weihai and Yantai) in the northern coastal areas of China for the investigation of trace element contamination. As, Cd, Cr, Cu, Hg, Pb and Zn were quantified. The risk of these trace elements to humans through bivalve consumption was then assessed. Results indicated that the concentrations of most of the studied trace element varied significantly with species: the average concentration of Cu in C. virginica was an order of magnitude higher than that in the remaining species; the average concentration of Zn was also highest in C. virginica; the average concentration of As, Cd and Pb was highest in R. philippinarum, C. farreri and A. irradians, respectively. Spatial differences in the concentrations of elements were generally less than those of interspecies, yet some elements such as Cr and Hg in the samples from different cities showed a significant difference in concentrations for some bivalve species. Trace element concentrations in edible tissues followed the order of Zn>Cu>As>Cd>Cr>Pb>Hg generally. Statistical analysis (one-way ANOVA) indicated that different species examined showed different bioaccumulation of trace elements. There were significant correlations between the concentrations of some elements. The calculated hazard quotients indicated in general that there was no obvious health risk from the intake of trace elements through bivalve consumption. But care must be taken considering the increasing amount of seafood consumption. PMID- 25128645 TI - Overexpression of a tobacco J-domain protein enhances drought tolerance in transgenic Arabidopsis. AB - DnaJ proteins constitute a DnaJ/Hsp40 family and are important regulators involved in diverse cellular functions. To date, the molecular mechanisms of DnaJ proteins involved in response to drought stress in plants are largely unknown. In this study, a putative DnaJ ortholog from Nicotiana tabacum (NtDnaJ1), which encodes a putative type-I J-protein, was isolated. The transcript levels of NtDnaJ1 were higher in aerial tissues and were markedly up-regulated by drought stress. Over-expression of NtDnaJ1 in Arabidopsis plants enhanced their tolerance to osmotic or drought stress. Quantitative determination of H2O2 accumulation has shown that H2O2 content increased in wild-type and transgenic seedlings under osmotic stress, but was significantly lower in both transgenic lines compared with the wild-type. Expression analysis of stress-responsive genes in NtDnaJ1 transgenic Arabidopsis revealed that there was significantly increased expression of genes involved in the ABA-dependent signaling pathway (AtRD20, AtRD22 and AtAREB2) and antioxidant genes (AtSOD1, AtSOD2, and AtCAT1). Collectively, these data demonstrate that NtDnaJ1 could be involved in drought stress response and its over-expression enhances drought tolerance possibly through regulating expression of stress-responsive genes. This study may facilitate our understandings of the biological roles of DnaJ protein-mediated abiotic stress in higher plants and accelerate genetic improvement of crop plants tolerant to environmental stresses. PMID- 25128646 TI - Characterization of two highly similar CBF/DREB1-like genes, PhCBF4a and PhCBF4b, in Populus hopeiensis. AB - The C-repeat binding factors (CBFs)/dehydration-responsive element-binding protein (DREBs) are a group of conserved transcription factors that play an important role in the response and adaptation to environmental stress in many plants. Two highly similar CBF/DREB1-like genes, PhCBF4a and PhCBF4b, were previously identified in Populus hopeiensis. In this paper, we describe the function of these proteins in detail in terms of abiotic stress tolerance. Phylogenic analysis suggests that PhCBF4a and PhCBF4b are expressed as two distinct alleles. Expression of both genes is induced mainly by dehydration, low temperature, and high-salinity. Agroinfiltration experiments in tobacco leaves revealed differential transcriptional activation of the genes, likely driven by differences in their C-terminal regions. When constitutively expressed in Arabidopsis, PhCBF4a and PhCBF4b induced elevated expression of the CBF/DREB1 regulons without prior stimulus, resulting in dwarfism, delayed flowering, and greater drought tolerance compared with vector controls. These results demonstrate that PhCBF4a and PhCBF4b are functional transcriptional regulators involved in the response of P. hopeiensis to abiotic stresses. PMID- 25128648 TI - Lysyl oxidase-like 2 (LOXL2) from stromal fibroblasts stimulates the progression of gastric cancer. AB - The aim of this study was to clarify the role of fibroblast-derived Lysyl oxidase like 2 (LOXL2) in the development of gastric cancer. The correlation between the clinicopathological features of 548 primary gastric carcinomas and LOXL2 expression in stromal cells was examined by immunohistochemistry. Two gastric cancer cell lines, OCUM-12 and NUGC-3, and cancer-associated fibroblasts (CAFs) were used in this in vitro study. The effect of fibroblast-derived LOXL2 on the motility of gastric cancer cells was analyzed by using a wound-healing assay, a double-chamber invasion assay, and western blot. LOXL2 expression in stromal cells was significantly associated with tumor invasion depth, lymph node metastasis, lymphatic invasion, venous invasion, and peritoneal dissemination. Multivariable logistic regression analysis revealed that LOXL2 expression in stromal cells could be an independent predictive parameter for the overall survival of patients. CAFs significantly stimulated the migration and invasion of OCUM-12 and NUGC-3 cells. This motility-stimulating ability of CAFs was inhibited by LOXL2 siRNA. Western blot analysis indicated that phosphorylation of focal adhesion kinase (FAK) in cancer cells was increased by the conditioned medium from CAFs, and was decreased by the conditioned medium from LOXL2 siRNA-treated CAFs. LOXL2 expression in stromal cells may be a useful prognostic factor for patients with gastric cancer. Fibroblast-derived LOXL2 may stimulate the motility of gastric cancer cells. PMID- 25128647 TI - Exploring therapeutic potentials of baicalin and its aglycone baicalein for hematological malignancies. AB - Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized. PMID- 25128649 TI - Molecular mechanisms of endometrial stromal sarcoma and undifferentiated endometrial sarcoma as premises for new therapeutic strategies. AB - Endometrial stromal sarcoma (ESS) and undifferentiated endometrial sarcoma (UES) are very rare gynecologic malignancies. Due to the rarity and heterogeneity of these tumors, little is known about their epidemiology, pathogenesis, and molecular pathology. Our previous studies have described deregulation of histone deacetylases expression in ESS/UES samples. Some of these enzymes can be inhibited by substances which are already approved for treatment of cutaneous T cell lymphoma. On the basis of published data, they may also provide a therapeutic option for ESS/UES patients. Our review focuses on molecular mechanisms of ESS/UES. It describes various aspects with special emphasis on alteration of histone deacetylation and its possible relevance for novel therapies. PMID- 25128650 TI - Embelin inhibits pancreatic cancer progression by directly inducing cancer cell apoptosis and indirectly restricting IL-6 associated inflammatory and immune suppressive cells. AB - Pancreatic cancer is an aggressive malignancy and unresponsive to conventional chemotherapies. Here, the anti-inflammatory and anti-tumor effects of embelin on pancreatic cancer were investigated. Embelin significantly attenuated cells invasion, proliferation and induced apoptosis through inhibition of STAT3 and activation of p53 signaling pathways. Embelin substantially reduced the tumorigenicity of pancreatic cancer cells in vivo, which was associated with reduced inflammatory cells and immune suppressive cells, IL-17A(+) Th17, GM CSF(+) Th, MDSCs and Treg, through inhibition of IL-6 secretion. Moreover, embelin decrease IL-6-induced STAT3 phosphorylation. In summary, embelin represents a novel therapeutic drug candidate for the clinical treatment of pancreatic cancer. PMID- 25128651 TI - An in vitro retinoblastoma human triple culture model of angiogenesis: a modulatory effect of TGF-beta. AB - Retinoblastoma is the most common intraocular tumour in children. In view of understanding the molecular mechanisms through which angiogenic switch on happens in the early phases of reciprocal interaction between tumour and cells constituting retinal microvessel, Transwell co-cultures constituted by human retinal endothelial cells (HREC), pericytes (HRPC), and human retinoblastoma cell line Y-79 were performed. Y-79 enhanced HREC proliferation, reduced by the introduction of HRPC in triple culture. In HREC/HRPC cultures, TGF-beta in media increased, decreasing in triple cultures. High VEGF levels in triple cultures witnessed the establishment of a strongly in vitro angiogenic environment. Y-79 induced in HREC an increase in c- and iPLA2, phospho-cPLA2, inducible COX-2 protein expressions, PLA2 activities and prostaglandin E2 (PGE2) release. These effects were attenuated when HRPC were introduced in triple culture. Moreover, antibody silencing of TGF-beta demonstrated a strong correlation between the signalling pathway triggered by TGF-beta of pericytal origin and the phospholipase activation and the modulation of PGE2 release. Inhibiting VEGFA effect, the HRPC loss in triple culture decreased, showing its modulatory effect on their survival. Relying on the data here presented, sustaining the pericytal survival in a tumour retinal environment could ensure the integrity of microvessels and the TGF-beta supply, essential for controlling aberrant endothelial pruning and angiogenesis. PMID- 25128652 TI - Betaglycan blocks metastatic behaviors in human granulosa cell tumors by suppressing NFkappaB-mediated induction of MMP2. AB - Metastatic ovarian granulosa cell tumors (GCT) exhibit loss of betaglycan. Here we test the hypothesis that betaglycan blocks GCT metastasis by suppressing NFkappaB/TGFbeta2-induced matrix metalloprotinease-2 (MMP2). Human GCT and a human GCT cell model demonstrated prominent MMP2 expression, which was dependent on NFkappaB activity and stimulated by TGFbeta2 in an NFkappaB-dependent manner. Betaglycan suppressed both basal and TGFbeta2-induced MMP2 expression and countered metastatic behaviors of GCT cells in non-adherent spheroid culture and in vivo xenograft models of metastasis. These data suggest that NFkappaB/TGFbeta2 promotes, and betaglycan impedes, the early stages of GCT metastasis, when tumor cells first invade the peritoneum. PMID- 25128653 TI - Does lesioning surgery have a role in the management of multietiological tremor in the era of Deep Brain Stimulation? AB - INTRODUCTION: Surgical management of tremor has evolved over the years with Deep Brain Stimulation (DBS) gradually supplanting lesioning as the mainstay in treatment. In this article, the largest of its kind from our country, we present our experience in the use of lesioning in the management of patients with multietiological tremors. These include not only common indications like Parkinson disease and essential tremor but also rare causes such as Pantothenate kinase associated neurodegeneration (PKAN), multiple sclerosis (MS) and Wilson disease. MATERIALS AND METHODS: Patients with medically refractory tremor who underwent surgery were included in the analysis. A comprehensive clinical and radiological evaluation was performed which was repeated 3 months postoperatively and at successive visits. Video documentation of was obtained at all visits. RESULTS: A total of 21 patients (18 men, 3 women) with an average age 37.7 years (range 21-65 years) underwent stereotactic thalamotomy/subthalamotomy at our institute between 2008 and 2013, for the treatment of medically refractory tremor of varying etiologies. The mean preoperative duration of symptoms was 11 years (range 10 months to 34 years). The median time to onset of improvement was 2 months (range 1 week to 8 months). Analyzing the improvement on the modified FTM scale, in part 1 the scores improved from 21.7 to 1.5, the part II subset improved from an average of 9.2 to 3.2 while the part III subset improved from an average of 14.1 to 4.1 postoperatively. This implied an excellent response in tremor while the other 2 components had a very good response. DISCUSSION: In this study we have for the first time objectively analyzed the tremor improvement with a modified FTM scale and have produced excellent results. We have also shown that tremor of various etiologies respond extremely well to lesioning surgery. While DBS continues to remain the treatment of choice in various types of bilateral tremor, lesioning is very successful in a carefully selected cohort of patients. We are of the opinion that in predominantly unilateral tremor or when the patient cannot afford DBS especially in a country like ours, lesioning surgery is an important tool in the armamentarium of the functional neurosurgeon. PMID- 25128654 TI - Octyl-cyanoacrylate skin adhesive is effective for wound closure in posterior spinal surgery without increased risk of wound complications. AB - OBJECTIVE: Few published studies have examined the complication profile after posterior spinal surgery wherein absorbable, subcuticular suture and cyanoacrylate skin adhesives (CSA) were used for incision closure. The purpose of this report is to compare the rate and profile of wound complications in a large number of patients who underwent posterior spinal surgery with CSA skin closure to rates of similar complications with standard nylon closure techniques. METHODS: The prospective database of all surgical cases maintained by the senior author was retrospectively reviewed. Three hundred eighty-two patients underwent posterior spinal surgery for degenerative, oncologic and traumatic pathology. Wound-related complications, including cerebrospinal fluid leak, wound infection and dehiscence were analyzed in all patients. RESULTS: These data establish that the incisions in patients who undergo posterior spinal surgery can be safely and successfully closed with subcuticular MonocrylTM and CSA without increased risk of CSF leak, wound infection or dehiscence. Rates of these complications were similar between the study population, a small subset of patients treated with traditional closure techniques and those in the established literature. CONCLUSIONS: CSA is a safe method to achieve ultimate skin closure in patients who undergo posterior spinal surgery without increased risk of wound-related complications, even in those patients undergoing intradural procedures. PMID- 25128655 TI - Epidemiology of a large telestroke cohort in the Delaware valley. AB - BACKGROUND: The American Heart Association/American Stroke Association has recently endorsed telestroke. Telestroke has enhanced stroke diagnosis, increased tPA administration and improved long-term outcomes. However, many of the publication on telemedicine so far have been review articles. OBJECTIVES: We investigated the epidemiological features of telestroke patients and evaluated the difference between the transferred and non-transferred cohorts. METHODS: We collected data on telestroke consultation, between January 2012 and June 2013, regarding patient's age, gender, diagnosis, NIHSS, onset-to-spoke time (OTS), tPA administration and transfer status. Further data was obtained on transferred patients regarding discharge and endovascular interventions. RESULTS: The means of age, NIHSS and OTS time were the following: 67.59 years, 7.65 and 11.28h respectively. The proportion of transferred patients was 12.04% (280/2324); lower than what was previously reported. The overall rate of IV tPA administration was 11.98%. Transferred patients had a significantly higher NIHSS mean (10.93 vs. 6.73; P<0.001), and were more likely to have received IV-tPA at onset (25.57 vs. 9.67; P<0.001). The age, gender proportion, stroke mimic proportion, and the mean of OTS did not differ between the two-groups (0.49 vs. 0.31; P=0.38). A logistic regression showed that NIHSS (OR=1.06, P<0.001) and tPA administration at onset (OR=2.78, P<0.001) predict the transfer. Of the transferred patients, 4.5% received endovascular intervention. The mortality rate of transferred patients was 12.9%. Other outcomes were the following: 52% discharge to rehabilitation facilities, 29% discharge to home, and 8% discharge to long-term nursing facilities. CONCLUSION: Telestroke network is increasing the frequency of tPA usage in acute ischemic stroke and may decrease the need for transfer. Our aim was to optimize the stroke therapy to shorten the hospital stay and to increase the discharge home. This allows a better functional outcome and an additional benefit of cost-saving for the hospitals. PMID- 25128656 TI - Hemiballism-hemidystonia after parietal lobe tumour resection. PMID- 25128657 TI - WITHDRAWN: The instability of Cdc42 network with graph-theoretic methods. AB - This article has been withdrawn at the request of the author(s) and/or editor due to some inconsistencies in the manuscript. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 25128658 TI - A model for enhanced and selective transport through biological membranes with alternating pores. AB - We investigate the outflux of ions through the channels in a cell membrane. The channels undergo an open/close cycle according to a periodic schedule. Our study is based both on theoretical considerations relying on homogenization theory, and on Monte Carlo numerical simulations. We examine the onset of a limiting boundary behavior characterized by a constant ratio between the outflux and the local density, in the large volume limit. The focus here is on the issue of selectivity, that is on the different behavior of the ion currents through the channel in the cases of the selected and non-selected species. PMID- 25128659 TI - Dynamic neural network-based robust observers for uncertain nonlinear systems. AB - A dynamic neural network (DNN) based robust observer for uncertain nonlinear systems is developed. The observer structure consists of a DNN to estimate the system dynamics on-line, a dynamic filter to estimate the unmeasurable state and a sliding mode feedback term to account for modeling errors and exogenous disturbances. The observed states are proven to asymptotically converge to the system states of high-order uncertain nonlinear systems through Lyapunov-based analysis. Simulations and experiments on a two-link robot manipulator are performed to show the effectiveness of the proposed method in comparison to several other state estimation methods. PMID- 25128660 TI - Irreversible membrane fouling abatement through pre-deposited layer of hierarchical porous carbons. AB - In this work, dual-templated hierarchical porous carbons (HPCs), produced from a coupled ice-hard templating approach, are shown to be a highly effective solution to the commonly occurring problem of irreversible fouling of low-pressure membranes used for pre-treatment in wastewater reuse. For the first time, dual templated HPCs, along with their respective counterparts - single-templated meso porous carbon (MPCs) (without macropores) - are tested in terms of their fouling reduction capacity and ability to remove different effluent organic matter fractions present in wastewater and compared with a commercially available powdered activated carbon (PAC). The synthesized HPCs provided exceptional fouling abatement, a 4-fold higher fouling reduction as compared to the previously reported best performing commercial PAC and ~2.5-fold better fouling reduction than their respective mesoporous counterpart. Thus, it is shown that not only mesoporosity, but macroporosity is also necessary to achieve high fouling reduction, thus emphasizing the need for dual templating. In the case of HPCs, the pre-deposition technique is also found to outperform the traditional sorbent-feed mixing approach, mainly in terms of removal of fouling components. Based on their superior performance, a high permeability (ultra-low-pressure) membrane consisting of the synthesized HPC pre-deposited on a large pore size membrane support (0.45 MUm membrane), is shown to give excellent pre-treatment performance for wastewater reuse application. PMID- 25128661 TI - Mode of membrane insertion of individual transmembrane segments in Mdl1 and Mdl2, multi-spanning mitochondrial ABC transporters. AB - The sorting of an individual transmembrane (TM) segment of multi-spanning membrane proteins by the TIM23 complex in the mitochondrial inner membrane is poorly understood. Using the Mgm1 fusion approach, we attempted to assess the membrane insertion of individual TM segments of Mdl1p and Mdl2p, mitochondrial ABC transporters. Although these transporters share high sequence similarity, our results show that their membrane sorting patterns differ and that specific residues in TM domains strongly influence membrane insertion or translocation. These data imply that TIM23-mediated membrane insertion highly depends on the TM domain sequence context. PMID- 25128662 TI - I want to quit education: a longitudinal study of stress and optimism as predictors of school dropout intention. AB - Prior research on school dropout has often focused on stable person- and institution-level variables. In this research, we investigate longitudinally perceived stress and optimism as predictors of dropout intentions over a period of four years, and distinguish between stable and temporary predictors of dropout intentions. Findings based on a nationally representative sample of 16-20 year olds in Switzerland (N = 4312) show that both average levels of stress and optimism as well as annually varying levels of stress and optimism affect dropout intentions. Additionally, results show that optimism buffers the negative impact of annually varying stress (i.e., years with more stress than usual), but not of stable levels of stress (i.e., stress over four years). The implications of the results are discussed according to a dynamic and preventive approach of school dropout. PMID- 25128663 TI - Toxoplasma gondii and Neospora caninum infections in goat abortions from Argentina. AB - The aims of this study were to identify the occurrence of Toxoplasma gondii and Neospora caninum abortions in goats from Argentina by serological, macroscopical and microscopical examination and bioassay, and to characterize the obtained isolates by molecular techniques. For this purpose, 25 caprine fetal fluids, 18 caprine fetal brains and 10 caprine placentas from 8 dairy/meat goat farms from Argentina were analyzed. Gestational age of the aborted fetuses was determined in 18 cases. Protozoal infections were detected by at least one of the applied diagnostic techniques in 44% (11/25) of examined fetuses; specifically, 24% (6/25) were positive to T. gondii, 8% (2/25) were positive to N. caninum and 12% (3/25) were positive to both parasites. In this study IFAT titers were similarly distributed in younger and older fetuses. Macroscopical and microscopical examination of one placenta revealed chalky nodules in the fetal cotyledons and normal intercotyledonary areas, as well as necrosis and calcification of mesenchymal cells in villi. Tachyzoites were observed in peritoneal wash from 2 mice inoculated with brain and a pool of brain and placenta of two fetuses. Cell culture growth of tachyzoites was achieved from one inoculated mouse, and confirmed as T. gondii by PCR. The T. gondii isolate was identified as atypical or non-canonical by nested-PCR-RFLP. This is the first study that investigated the involvement of N. caninum and T. gondii in cases of goat abortion in Argentina. PMID- 25128665 TI - Synthesis of natural-like acylphloroglucinols with anti-proliferative, anti oxidative and tube-formation inhibitory activity. AB - Two series of natural and natural-like mono- and bicyclic acylphloroglucinols derived from secondary metabolites in the genus Hypericum (Hypericaceae) were synthesised and tested in vitro for anti-proliferative and tube-formation inhibitory activity in human microvascular endothelial cells (HMEC-1). In addition, their anti-oxidative activity was determined via an ORAC-assay. The first series of compounds (4a-e) consisted of geranylated monocyclic acylphloroglucinols with varying aliphatic acyl substitution patterns, which were subsequently cyclised to the corresponding 2-methyl-2-prenylchromane derivatives (5a and 5d). The second series involved compounds containing a 2,2 dimethylchromane skeleton with differing aromatic acyl substitution (6a-d and 7a e). Compound 7a, (5,7-dihydroxy-2,2-dimethylchroman-6-yl)-(3,4 dihydroxyphenyl)methanone), showed the highest in vitro anti-proliferative activity with an IC50 of 0.88 +/- 0.08 MUM and a remarkable anti-oxidative activity of 2.8 +/- 0.1 TE from the ORAC test. Interestingly, the high anti proliferative activity of these acylphloroglucinols was not associated with tube formation inhibition. Compounds (E)-1-(3-(3,7-dimethylocta-2,6-dien-1-yl)-2,4,6 trihydroxyphenyl)-2-methylbutan-1-one (4d) and (5,7-dihydroxy-2,2-dimethylchroman 6-yl)(3,4-dimethoxyphenyl)methanone (6a) exhibited moderate to weak anti proliferative effects (IC50 11.0 +/- 1 MUM and 48.0 +/- 4.3 MUM, respectively) and inhibited the capillary-like tube formation of HMEC-1 in vitro, whereas 7a was inactive. The most active compound in the ORAC assay was 7c, which exhibited an anti-oxidative effect of 6.6 +/- 1.0 TE. However, this compound showed only weak activity during the proliferation assay (IC50 53.8 +/- 0.3) and did not inhibit tube-formation. PMID- 25128664 TI - Identification of anxiety sensitivity classes and clinical cut-scores in a sample of adult smokers: results from a factor mixture model. AB - Anxiety sensitivity (AS), a multidimensional construct, has been implicated in the development and maintenance of anxiety and related disorders. Recent evidence suggests that AS is a dimensional-categorical construct within individuals. Factor mixture modeling was conducted in a sample of 579 adult smokers (M age=36.87 years, SD=13.47) to examine the underlying structure. Participants completed the Anxiety Sensitivity Index-3 and were also given a Structured Clinical Interview for DSM-IV-TR. Three classes of individuals emerged, a high AS (5.2% of the sample), a moderate AS (19.0%), and a normative AS class (75.8%). A cut-score of 23 to identify high AS individuals, and a cut-score of 17 to identify moderate-to-high AS individuals were supported in this study. In addition, the odds of having a concurrent anxiety disorder (controlling for other Axis I disorders) were the highest in the high AS class and the lowest in the normative AS class. PMID- 25128666 TI - Novel alkylphospholipid-DTC hybrids as promising agents against endocrine related cancers acting via modulation of Akt-pathway. AB - A new series of 2-(alkoxy(hydroxy)phosphoryloxy)ethyl dialkylcarbodithioate derivatives was synthesized and evaluated against endocrine related cancers, acting via modulation of Akt-pathway. Eighteen compounds were active at 7.24-100 MUM against MDA-MB-231 or MCF-7 cell lines of breast cancer. Three compounds (14, 18 and 22) were active against MCF-7 cells at IC50 significantly better than miltefosine and most of the compounds were less toxic towards non-cancer cell lines, HEK-293. On the other hand, twelve compounds exhibited cell growth inhibiting activity against prostate cancer cell lines, either PC-3 or DU-145 at 14.69-95.20 MUM. While nine of these were active against both cell lines. The most promising compounds 14 and 18 were about two and five fold more active than miltefosine against DU-145 and MCF-7 cell lines respectively and significantly down regulated phospho-Akt. Possibly anti-cancer and pro-apoptotic activity was mostly due to blockade of Akt-pathway. PMID- 25128667 TI - Chalcone based azacarboline analogues as novel antitubulin agents: design, synthesis, biological evaluation and molecular modelling studies. AB - The present study involves the design of a series of 3-aryl-9-acetyl pyridazino[3,4-b]indoles as constrained chalcone analogues. A retrosynthetic route was proposed for the synthesis of target compounds. All the synthesized compounds were evaluated for in-vitro cytotoxicity against THP-1, COLO-205, HCT 116 and A-549 human cancer cell lines. The results indicated that 2a, 3a, 5a and 6a possessed significant cytotoxic potential with an IC50 value ranging from 1.13 to 5.76 MUM. Structure activity relationship revealed that the nature of both Ring A and Ring B influences the activity. Substitution of methoxy groups on the phenyl ring (Ring A) and unsubstituted phenyl ring (Ring B) were found to be the preferred structural features. The most potent compound 2a was further tested for tubulin inhibition. Compound 2a was found to significantly inhibit the tubulin polymerization (IC50 value - 2.41 MUM against THP-1). Compound 2a also caused disruption of microtubule assembly as evidenced by Immunoflourescence technique. The significant cytotoxicity and tubulin inhibition by 2a was rationalized by molecular modelling studies. The most potent structure was docked at colchicine binding site (PDB ID-1SA0) and was found to be stabilized in the cavity via various hydrophobic and hydrogen bonding interactions. PMID- 25128668 TI - Statins in therapy: understanding their hydrophilicity, lipophilicity, binding to 3-hydroxy-3-methylglutaryl-CoA reductase, ability to cross the blood brain barrier and metabolic stability based on electrostatic molecular orbital studies. AB - The atomic electrostatic potentials calculated by the CHELPG method have been shown to be sensitive indicators of the gas phase and solution properties of the statins. Solvation free energies in water, n-octanol and n-octane have been determined using the SMD solvent model. The percentage hydrophilicity and hydrophobicity (or lipophilicity) of the statins in solution have been determined using (a) the differences in solvation free energies between n-octanol and n octane as a measure of hydrophilicity, and the solvation energy in octane as a measure of hydrophobicity (b) the sum of the atomic electrostatic charges on the hydrogen bonding and polar bonding nuclei of the common pharmacophore combined with a solvent measure of hydrophobicity, and (c) using the buried surface areas after statin binding to HMGCR to calculate the hydrophobicity of the bound statins. The data suggests that clinical definitions of statins as either "hydrophilic" or "lipophilic" based on experimental partition coefficients are misleading. An estimate of the binding energy between rosuvastatin and HMGCR has been made using: (a) a coulombic electrostatic interaction model, (b) the calculated desolvation and resolvation of the statin in water, and (c) the first shell transfer solvation energy as a proxy for the restructuring of the water molecules immediately adjacent to the active binding site of HMGCR prior to binding. Desolvation and resolvation of the statins before and after binding to HMGCR are major determinants of the energetics of the binding process. An analysis of the amphiphilic nature of lovastatin anion, acid and lactone and fluvastatin anion and their abilities to cross the blood brain barrier has indicated that this process may be dominated by desolvation and resolvation effects, rather than the statin molecular size or statin-lipid interactions within the bilayer. The ionization energy and electron affinity of the statins are sensitive physical indicators of the ease that the various statins can undergo endogenous oxidative metabolism. The absolute chemical hardness is also an indicator of the stability of the statins, and may be a useful indicator for drug design. PMID- 25128669 TI - Investigation of in vitro anticancer and DNA strap interactions in live cells using carboplatin type Cu(II) and Zn(II) metalloinsertors. AB - A series of carboplatin type Cu(II) and Zn(II) metalloinsertors (1-8) having beta diketone analogues and biologically significant cyclobutane-1,1-dicarboxylic acid have been synthesized and characterized by spectral and analytical methods. The binding and cleavage propensity of these metalloinsertors on DNA and their cytotoxic effects in live cells have been explored. From the gel electrophoresis study, it is observed that the complexes 1-8 cleave pBR322 DNA via a hydrolytic mechanism induced by hydroxyl radical scavengers, DMSO and EtOH as the reactive oxygen species (ROS). In vivo antitumor efficacy has been studied on EAC tumor bearing mice which is assessed by mean survival time, effect on hematological parameters and solid tumor volume. The results strongly support that complex 1 shows potent antitumor effect against EAC and higher than the standard drug carboplatin. Moreover, the cytotoxicity of the complexes, screened on a panel of human cancerous cell lines viz., human cervical cancer cells (HeLa), human breast adenocarcinoma cells (MCF-7), human laryngeal epithelial carcinoma cells (HEp-2), human liver carcinoma cells (Hep G2) and non-cancerous NIH 3T3 mouse embryonic fibroblasts cell lines, reveals that complex 1 exhibits a better anticancer activity than other complexes and standards. PMID- 25128670 TI - Present status of quinoxaline motifs: excellent pathfinders in therapeutic medicine. AB - Quinoxalines belong to a class of excellent heterocyclic scaffolds owing to their wide biological properties and diverse therapeutic applications in medicinal research. They are complementary in shapes and charges to numerous biomolecules they interact with, thereby resulting in increased binding affinity. The pharmacokinetic properties of drugs bearing quinoxaline cores have shown them to be relatively easy to administer either as intramuscular solutions, oral capsules or rectal suppositories. This work deals with recent advances in the synthesis and pharmacological diversities of quinoxaline motifs which might pave ways for novel drugs development. PMID- 25128671 TI - Structure-activity relationships and molecular modeling studies of novel arylpiperazinylalkyl 2-benzoxazolones and 2-benzothiazolones as 5-HT(7) and 5 HT(1A) receptor ligands. AB - A novel series of arylpiperazinylalkyl 2-benzoxazolones and 2-benzothiazolones 18 38 was designed, synthesized and tested to evaluate their affinity for the 5-HT7 and 5-HT1A receptors. Compounds with a 2-benzothiazolone nucleus generally had affinity values higher than the corresponding 2-benzoxazolone compounds. In particular, derivatives possessing a six or seven carbon chain linker between 2 benzothiazolone and arylpiperazine had Ki values in the subnanomolar range for the 5-HT1A receptor and in the low nanomolar range for the 5-HT7 receptor, indicating that they may be interesting dual ligands. Molecular modeling studies revealed different docking poses for the investigated compounds in homology models of 5-HT1A and 5-HT7 receptors, which explained their experimentally determined affinities and general low selectivity. Additionally, structural interaction fingerprints analysis identified the important amino acid residues for the specific interactions of long-chain arylpiperazines within the binding pockets of both serotonin receptors. PMID- 25128672 TI - The impact of REACH on classification for human health hazards. AB - The REACH Regulation represents a major piece of chemical legislation in the EU and requires manufacturers and importers of chemicals to assess the safety of their substances. The classification of substances for their hazards is one of the crucial elements in this process. We analysed the effect of REACH on classification for human health endpoints by comparing information from REACH registration dossiers with legally binding, harmonised classifications. The analysis included 142 chemicals produced at very high tonnages in the EU, the majority of which have already been assessed in the past. Of 20 substances lacking a harmonised classification, 12 chemicals were classified in REACH registration dossiers. More importantly, 37 substances with harmonised classifications for human health endpoints had stricter classifications in registration dossiers and 29 of these were classified for at least one additional endpoint not covered by the harmonised classification. Substance-specific analyses suggest that one third of these additional endpoints emerged from experimental studies performed to fulfil information requirements under REACH, while two thirds resulted from a new assessment of pre-REACH studies. We conclude that REACH leads to an improved hazard characterisation even for substances with a potentially good data basis. PMID- 25128673 TI - Reducing the number of fish in bioconcentration studies with general chemicals by reducing the number of test concentrations. AB - Fish bioconcentration test guidelines generally require that bioconcentration factors (BCFs) are determined at two exposure concentrations. However, recent revisions to the OECD test guideline for bioconcentration testing (TG 305) provide the option to use only one exposure concentration, when justification is provided, although two concentrations may still be required for some regulatory purposes. Recently, this justification has been demonstrated for plant protection product active ingredients. To determine whether this justification has a broader validity for general chemicals, an analysis of 236 BCF studies on general chemicals was conducted. The results presented here again demonstrate that BCF values do not significantly differ between concentrations when more than one concentration is used. This relationship is particularly strong for BCFs ?1000L/kg, which is beneficial, since only chemicals with BCFs >2000L/kg may require regulatory action. This analysis therefore provides a data-driven rationale for using the one test concentration approach for general chemical substances and thus could contribute to a substantial reduction in the use of fish in bioconcentration tests. PMID- 25128674 TI - Spectroscopic, crystal structural and electrochemical studies of zinc(II)-Schiff base complex obtained from 2,3-diaminobenzene and 2-hydroxy naphthaldehyde. AB - Mononuclear zinc(II) complex, [Zn(II)L], where L is a dianionic ligand, has been synthesized and characterized by elemental analysis, electronic, IR and NMR [(1)H, (13)C, DEPT, (1)H-(1)H COSY, ROESY, HSQC and HMBC] spectroscopic techniques. Structural analysis of the complex by single crystal X-ray crystallography shows the presence of a distorted square planar coordination geometry (NNOO) of the metal center. The crystal of the title complex C28H18N2O2Zn belongs to the orthorhombic system with space group Pmn21. Electrochemical behavior of the Zn(II)L complex has been investigated by cyclic voltammetry on glassy carbon and platinum electrodes in DMF at 100 mV/s scan rate. PMID- 25128675 TI - Degradation of environment pollutant dyes using phytosynthesized metal nanocatalysts. AB - We present for the first time biogenic reduction and stabilization of gold and silver ions at room temperature using fruit juice of Punica granatum. The formation, morphology and crystalline structure of the synthesized nanoparticles are determined using UV-Visible, XRD and TEM. An attempt to reveal the partial role of phenolic hydroxyls in the reduction of Au(3+) and Ag(+) is done through FTIR analysis. The synthesized nanoparticles are used as potential catalysts in the degradation of a cationic phenothiazine dye, an anionic mono azo dye and a cationic fluorescent dye. The calculated values of percentage removal of dyes and the rate constants from pseudo first order kinetic data fit give a comparative study on degradation of organic dyes in presence of prepared gold and silver nanoparticles. PMID- 25128676 TI - Activity study of biogenic spherical silver nanoparticles towards microbes and oxidants. AB - The eco-friendly approach for the green synthesis of silver nanoparticles (SNP) using Terminalia bellirica (T. bellirica) fruit extract is reported herein. Initially formation of SNP was noticed through visual color change from yellow to reddish brown and further analyzed by surface plasmonic resonance (SPR) band at 429 nm using UV-Vis spectroscopy. Identification of different polyphenols present in T. bellirica extract was done using High Pressure Liquid Chromatography (HPLC). Aqueous T. bellirica extract contains high amount of gallic acid which is major secondary metabolite responsible for the reduction and stabilization process. It was established by analyses of extracts before and after reduction using HPLC. Formation of spherical SNP was characterized by Transmission Electron Microscopy (TEM) analysis. X-ray Diffraction (XRD) study revealed crystalline nature of SNP. Presence of different functional groups on the surface of SNP was evidenced by Fourier Transform Infrared Spectroscopy (FTIR) study. A plausible mechanism of reduction and stabilization processes involved in the synthesis of stable SNP was also explained based on HPLC and FTIR data. In addition, the synthesized SNP was tested for antibacterial and antioxidant activities. SNP showed good antimicrobial activity against both gram positive (S. aureus) and gram negative (E. coli) bacteria. It also showed good antioxidant activity compared to ascorbic acid as standard antioxidant by using standard DPPH method. PMID- 25128677 TI - Corona discharge ionization of paracetamol molecule: peak assignment. AB - Ionization of paracetamol was investigated using ion mobility spectrometry equipped with a corona discharge ionization source. The measurements were performed in the positive ion mode and three peaks were observed in the ion mobility spectrum. Experimental evidence and theoretical calculations were used to correlate the peaks to related ionic species of paracetamol. Two peaks were attributed to protonated isomers of paracetamol and the other peak was attributed to paracetamol fragment ions formed by dissociation of the N-C bond after protonation of the nitrogen atom. It was observed that three sites of paracetamol compete for protonation and their relative intensities, depending on the sample concentration. The ratio of ion products could be predicted from the internal proton affinity of the protonation sites at each concentration. PMID- 25128678 TI - Vibrational spectroscopic studies and molecular docking of 10,10 Dimethylanthrone. AB - FT-IR and FT-Raman spectra of 10,10-Dimethylanthrone were recorded and analyzed. The vibrational wavenumbers were computed using DFT quantum chemical calculations. The data obtained from wavenumber calculations are used to assign vibrational bands obtained experimentally. In its most stable form, the title compound maintains C2v symmetry as determined by XRD results, where both methyl groups are staggered with respect to the corresponding C23-C24 and C23-C28 bonds. The geometrical parameters (B3LYP/6-311++G(d,p)(5D,7F)) of the title compound are in agreement with the XRD results. The calculated HOMO and LUMO energies allow the calculations of atomic and molecular properties and they also showed that charge transfer occurs in the molecule. A detailed molecular picture of the title compound and its interactions were obtained from NBO analysis. As seen from the MEP map, negative potential regions are localized over the carbonyl group and are possible sites for electrophilic attack. The title compound, 10,10 Dimethylanthrone forms a stable complex with human topoisomerase-II as is evident from the ligand-receptor interactions and show appreciable antineoplastic activity. PMID- 25128679 TI - CuO nanostructures: optical properties and morphology control by pyridinium-based ionic liquids. AB - Copper oxide nanostructures have been synthesized by a simple reflux method in aqueous medium of pyridinium based ionic liquids. The structural and optical properties of CuO nanostructures were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence spectroscopy (PL) and UV visible. The morphologies of the nanostructures can be controlled by changing the amount of NaOH and ionic liquids. The results show that the use identical pyridinium based ionic liquids in ratio of 4:1 NaOH/Cu(OAc)2?H2O yield minor differences in morphology of CuO nanostructures. Different morphologies of CuO nanostructures were obtained by changing the ratio NaOH/Cu(OAc)2?H2O to 2:1. Ionic liquids play an important role on optical properties of CuO nanostructures. The results of optical measurements of the CuO nanostructures illustrate that band gaps are estimated to be 1.67-1.85 eV. PL patterns studies show that the ionic liquids can be effect on PL patterns of the samples. The reasons of these phenomena are discussed. PMID- 25128680 TI - Investigation on the interaction between an antimicrobial in aquaculture, malachite green and hemocyanin from mud crab Scylla paramamosain. AB - Interaction between malachite green and hemocyanin of crab plays a crucial role in the metabolism, distribution, and efficacy of toxic dyes in aquaculture. The mechanism of interaction between malachite green and Hc from mud crab was studied by using multi-spectral methods and molecular modeling in this work. The spectroscopic and thermodynamic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes of -14.85(+/-1.86) kJ mol(-1) and 30.38(+/-5.21) J mol(-1) K(-1), respectively. The binding sites of malachite green in hemocyanin mainly locate in the interface of protein. The hydrophobic and electrostatic forces are the primary contributors to the interaction between hemocyanin and malachite green. The results of ultraviolet vis absorbance, circular dichroism, and synchronous fluorescence spectroscopy suggest that the binding of malachite green to hemocyanin induces some conformational changes of protein. PMID- 25128681 TI - Synthesis of zinc chlorophyll materials for dye-sensitized solar cell applications. AB - To design sensitizers for dye sensitized solar cells (DSSCs), a series of zinc chlorins with different substituents were synthesized. Novel zinc methyl 3 devinyl-3-hydroxymethyl-20-phenylacetylenylpyropheophorbide-a (ZnChl-1), zinc methyl 20-bromo-3-devinyl-3-hydroxymethylpyropheophorbide-a (ZnChl-2), zinc methyl 3-devinyl-3-hydroxymethyl-pyropheophorbide-a (ZnChl-3), zinc propyl 3 devinyl-3-hydroxymethyl-pyropheophorbide-a (ZnChl-4) were synthesized and their photovoltaic performances were evaluated in dye-sensitized solar cells. Photoelectrodes with a 7 MUm thick nanoporous layer and a 5 MUm thick light scattering layer were used to fabricate dye sensitized solar cells. The best efficiency was obtained with ZnChl-2 sensitizer. ZnChl-2 gave a Jsc of 3.5 mA/cm(2), Voc of 412 mV, FF of 0.56 and an overall conversion efficiency of 0.81 at full sun (1000 W m(-2)). PMID- 25128682 TI - Synthesis, spectroscopic and electrochemical performance of pasted beta-nickel hydroxide electrode in alkaline electrolyte. AB - beta-Nickel hydroxide (beta-Ni(OH)2) was successfully synthesized using precipitation method. The structure and property of the beta-Ni(OH)2 were characterized by X-ray diffraction (XRD), Fourier Transform infra-red (FT-IR), Raman spectra and thermal gravimetric-differential thermal analysis (TG-DTA). The results of the FTIR spectroscopy and TG-DTA studies indicate that the beta Ni(OH)2 contains water molecules and anions. The microstructural and composition studies have been performed using Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX) analysis. A pasted-type electrode is prepared using beta Ni(OH)2 powder as the active material on a nickel sheet as a current collector. Cyclic voltammetry (CV) and Electrochemical impedance spectroscopy (EIS) studies were performed to evaluate the electrochemical performance of the beta-Ni(OH)2 electrode in 6M KOH electrolyte. CV curves showed a pair of strong redox peaks as a result of the Faradaic redox reactions of beta-Ni(OH)2. The proton diffusion coefficient (D) for the present beta-Ni(OH)2 electrode material is found to be 1.44*10(-12) cm(2) s(-1). Further, electrochemical impedance studies confirmed that the beta-Ni(OH)2 electrode reaction processes are diffusion controlled. PMID- 25128684 TI - Fusion of multi-tracer PET images for dose painting. AB - PET imaging with FluoroDesoxyGlucose (FDG) tracer is clinically used for the definition of Biological Target Volumes (BTVs) for radiotherapy. Recently, new tracers, such as FLuoroThymidine (FLT) or FluoroMisonidazol (FMiso), have been proposed. They provide complementary information for the definition of BTVs. Our work is to fuse multi-tracer PET images to obtain a good BTV definition and to help the radiation oncologist in dose painting. Due to the noise and the partial volume effect leading, respectively, to the presence of uncertainty and imprecision in PET images, the segmentation and the fusion of PET images is difficult. In this paper, a framework based on Belief Function Theory (BFT) is proposed for the segmentation of BTV from multi-tracer PET images. The first step is based on an extension of the Evidential C-Means (ECM) algorithm, taking advantage of neighboring voxels for dealing with uncertainty and imprecision in each mono-tracer PET image. Then, imprecision and uncertainty are, respectively, reduced using prior knowledge related to defects in the acquisition system and neighborhood information. Finally, a multi-tracer PET image fusion is performed. The results are represented by a set of parametric maps that provide important information for dose painting. The performances are evaluated on PET phantoms and patient data with lung cancer. Quantitative results show good performance of our method compared with other methods. PMID- 25128683 TI - Automatic atlas-based three-label cartilage segmentation from MR knee images. AB - Osteoarthritis (OA) is the most common form of joint disease and often characterized by cartilage changes. Accurate quantitative methods are needed to rapidly screen large image databases to assess changes in cartilage morphology. We therefore propose a new automatic atlas-based cartilage segmentation method for future automatic OA studies. Atlas-based segmentation methods have been demonstrated to be robust and accurate in brain imaging and therefore also hold high promise to allow for reliable and high-quality segmentations of cartilage. Nevertheless, atlas-based methods have not been well explored for cartilage segmentation. A particular challenge is the thinness of cartilage, its relatively small volume in comparison to surrounding tissue and the difficulty to locate cartilage interfaces - for example the interface between femoral and tibial cartilage. This paper focuses on the segmentation of femoral and tibial cartilage, proposing a multi-atlas segmentation strategy with non-local patch based label fusion which can robustly identify candidate regions of cartilage. This method is combined with a novel three-label segmentation method which guarantees the spatial separation of femoral and tibial cartilage, and ensures spatial regularity while preserving the thin cartilage shape through anisotropic regularization. Our segmentation energy is convex and therefore guarantees globally optimal solutions. We perform an extensive validation of the proposed method on 706 images of the Pfizer Longitudinal Study. Our validation includes comparisons of different atlas segmentation strategies, different local classifiers, and different types of regularizers. To compare to other cartilage segmentation approaches we validate based on the 50 images of the SKI10 dataset. PMID- 25128685 TI - Providers' perspectives on treating psychogenic nonepileptic seizures: frustration and hope. AB - Recent diagnostic and treatment advances in psychogenic nonepileptic seizures (PNES) have the potential to improve care for patients, but little is known about the current state of PNES care delivery in the Veterans Health Administration (VA). We conducted semistructured interviews with 74 health-care clinicians and workers in the VA, eliciting provider perceptions of PNES care. Data were analyzed according to principles of Grounded Theory. The results revealed variation in care and two emergent domain themes of frustration and hope. Frustration was manifest in subthemes including Complexity, Patient Acceptance, Uncertainty About Treatment, Need for Evidence-based Treatment, and Failure of Cross-Disciplinary Collaboration between neurologists and mental health providers. Hope encompassed subthemes of Positive Attitudes, Developing Cross Disciplinary Treatment, and Specific PNES Care. Increased resources for diagnosing, treating, and researching PNES have improved awareness of the disorder. More research is needed to understand patients' and caregivers' perceptions of PNES care. PMID- 25128686 TI - A predictive risk model for medical intractability in epilepsy. AB - OBJECTIVE: This study aimed to investigate early predictors (6 months after diagnosis) of medical intractability in epilepsy. METHODS: All children <12 years of age having two or more unprovoked seizures 24 h apart at Xinhua Hospital between 1992 and 2006 were included. Medical intractability was defined as failure, due to lack of seizure control, of more than 2 antiepileptic drugs at maximum tolerated doses, with an average of more than 1 seizure per month for 24 months and no more than 3 consecutive months of seizure freedom during this interval. Univariate and multivariate logistic regression models were performed to determine the risk factors for developing medical intractability. Receiver operating characteristic curve was applied to fit the best compounded predictive model. RESULTS: A total of 649 patients were identified, out of which 119 (18%) met the study definition of intractable epilepsy at 2 years after diagnosis, and the rate of intractable epilepsy in patients with idiopathic syndromes was 12%. Multivariate logistic regression analysis revealed that neurodevelopmental delay, symptomatic etiology, partial seizures, and more than 10 seizures before diagnosis were significant and independent risk factors for intractable epilepsy. The best model to predict medical intractability in epilepsy comprised neurological physical abnormality, age at onset of epilepsy under 1 year, more than 10 seizures before diagnosis, and partial epilepsy, and the area under receiver operating characteristic curve was 0.7797. This model also fitted best in patients with idiopathic syndromes. CONCLUSION: A predictive model of medically intractable epilepsy composed of only four characteristics is established. This model is comparatively accurate and simple to apply clinically. PMID- 25128687 TI - Constitutional chromoanasynthesis: description of a rare chromosomal event in a patient. AB - Structural alterations in chromosomes are a frequent cause of cancers and congenital diseases. Recently, the phenomenon of chromosome crisis, consisting of a set of tens to hundreds of clustered genomic rearrangements, localized in one or a few chromosomes, was described in cancer cells under the term chromothripsis. Better knowledge and recognition of this catastrophic chromosome event has brought to light two distinct entities, chromothripsis and chromoanasynthesis. The complexity of these rearrangements and the original descriptions in tumor cells initially led to the thought that it was an acquired anomaly. In fact, a few patients have been reported with constitutional chromothripsis or chromoanasynthesis. Using microarray we identified a very complex chromosomal rearrangement in a patient who had a cytogenetically visible rearrangement of chromosome 18. The rearrangement contained more than 15 breakpoints localized on a single chromosome. Our patient displayed intellectual disability, behavioral troubles and craniofacial dysmorphism. Interestingly, the succession of duplications and triplications identified in our patient was not clustered on a single chromosomal region but spread over the entire chromosome 18. In the light of this new spectrum of chromosomal rearrangements, this report outlines the main features of these catastrophic events and discusses the underlying mechanism of the complex chromosomal rearrangement identified in our patient, which is strongly evocative of a chromoanasynthesis. PMID- 25128689 TI - Population data of 17 Y-STR loci in Nanyang Han population from Henan Province, Central China. PMID- 25128688 TI - Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with smallpox vaccine does not compromise vaccine protection in mice challenged with ectromelia virus. AB - Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and buffalopox continue to cause morbidity in the human population. Monkeypox virus remains a significant agent of morbidity and mortality in Africa. Furthermore, monkeypox virus's broad host-range and expanding environs make it of particular concern as an emerging human pathogen. Monkeypox virus and variola virus (the etiological agent of smallpox) are both potential agents of bioterrorism. The first line response to orthopoxvirus disease is through vaccination with first generation and second-generation vaccines, such as Dryvax and ACAM2000. Although these vaccines provide excellent protection, their widespread use is impeded by the high level of adverse events associated with vaccination using live, attenuated virus. It is possible that vaccines could be used in combination with antiviral drugs to reduce the incidence and severity of vaccine-associated adverse events, or as a preventive in individuals with uncertain exposure status or contraindication to vaccination. We have used the intranasal mousepox (ectromelia) model to evaluate the efficacy of vaccination with Dryvax or ACAM2000 in conjunction with treatment using the broad spectrum antiviral, brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the severity of vaccination-associated lesion development. Although the immune response to vaccination was quantifiably attenuated, vaccination combined with BCV treatment did not alter the development of full protective immunity, even when administered two days following ectromelia challenge. Studies with a non replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of attenuating the immune response following vaccination with live virus was, as expected, by limiting viral replication and not through inhibition of the immune system. These studies suggest that, in the setting of post-exposure prophylaxis, co-administration of BCV with vaccination should be considered a first response to a smallpox emergency in subjects of uncertain exposure status or as a means of reduction of the incidence and severity of vaccine-associated adverse events. PMID- 25128690 TI - Identification of body fluid-specific DNA methylation markers for use in forensic science. AB - DNA methylation, which occurs at the 5'-position of the cytosine in CpG dinucleotides, has great potential for forensic identification of body fluids, because tissue-specific patterns of DNA methylation have been demonstrated, and DNA is less prone to degradation than proteins or RNA. Previous studies have reported several body fluid-specific DNA methylation markers, but DNA methylation differences are sometimes low in saliva and vaginal secretions. Moreover, specific DNA methylation markers in four types of body fluids (blood, saliva, semen, and vaginal secretions) have not been investigated with genome-wide profiling. Here, we investigated novel DNA methylation markers for identification of body fluids for use in forensic science using the Illumina HumanMethylation 450K bead array, which contains over 450,000 CpG sites. Using methylome data from 16 samples of blood, saliva, semen, and vaginal secretions, we first selected 2986 hypermethylated or hypomethylated regions that were specific for each type of body fluid. We then selected eight CpG sites as novel, forensically relevant DNA methylation markers: cg06379435 and cg08792630 for blood, cg26107890 and cg20691722 for saliva, cg23521140 and cg17610929 for semen, and cg01774894 and cg14991487 for vaginal secretions. These eight selected markers were evaluated in 80 body fluid samples using pyrosequencing, and all showed high sensitivity and specificity for identification of the target body fluid. We suggest that these eight DNA methylation markers may be good candidates for developing an effective molecular assay for identification of body fluids in forensic science. PMID- 25128691 TI - High isolation rates of multidrug-resistant bacteria from water and carpets of mosques. AB - OBJECTIVE: There is little information regarding the isolation of antimicrobial resistant potentially pathogenic bacteria from water and carpets of mosques worldwide. The objective of the present investigation is to determine the bacteriological quality of water and carpets of mosques in Elkhomes city in Libya. METHODS: Potentially pathogenic bacteria were isolated from water samples (n=44) and dust samples from carpets (n=50) of 50 mosques in Elkhomes city, Libya, using standard bacteriological procedures. Susceptibility of isolated bacteria to antimicrobial agents was determined by the disc-diffusion method. RESULTS: Of the water samples examined, 12 (27.3%) were positive for Escherichia coli, 10 (22.7%) for Klebsiella spp., and 15 (34.1%) for other enteric bacteria. Of the dust samples of carpets examined, 6 (12%) were positive for E. coli, 33 (66%) for Klebsiella spp., and 30 (60%) for Staphylococcus spp. Multidrug resistance (MDR, resistance to three or more antimicrobial groups) was found among 48.7% (19/37) and 46.9% (30/64) of the examined enterobacteria from water and carpets, respectively, and among 66.7% (20/30) of Staphylococcus spp. from carpets. In addition, methicillin-resistant Staphylococcus aureus (MRSA) was isolated from a carpet of one mosque. CONCLUSION: Presence of multidrug-resistant potentially pathogenic bacteria in examined water and carpets indicate that mosques as communal environments may play a role in the spread of multidrug resistant bacteria in the community and pose a serious health risk to worshipers. PMID- 25128692 TI - NAD-dependent ADP-ribosylation of the human antimicrobial and immune-modulatory peptide LL-37 by ADP-ribosyltransferase-1. AB - LL-37 is a cationic peptide belonging to the cathelicidin family that has antimicrobial and immune-modulatory properties. Here we show that the mammalian mono-ADP-ribosyltransferase-1 (ART1), which selectively transfers the ADP-ribose moiety from NAD to arginine residues, ADP-ribosylates LL-37 in vitro. The incorporation of ADP-ribose was first observed by Western blot analysis and then confirmed by MALDI-TOF. Mass-spectrometry showed that up to four of the five arginine residues present in LL-37 could be ADP-ribosylated on the same peptide when incubated at a high NAD concentration in the presence of ART1. The attachment of negatively charged ADP-ribose moieties considerably alters the positive charge of the arginine residues thus reducing the cationicity of LL-37. The cationic nature of LL-37 is key for its ability to interact with cell membranes or negatively charged biomolecules, such as DNA, RNA, F-actin and glycosaminoglycans. Thus, the ADP-ribosylation of LL-37 is expected to have the potential to modulate LL-37 biological activities in several physiological and pathological settings. PMID- 25128693 TI - Vascular endothelial function and blood pressure regulation in afferent autonomic failure. AB - BACKGROUND: Familial dysautonomia (FD) is a rare hereditary disease characterized by loss of afferent autonomic neural fiber signaling and consequent profound impairment of arterial baroreflex function and blood pressure regulation. Whether vascular endothelial dysfunction contributes to defective vasomotor control in this form of afferent autonomic failure is not known. METHODS: We assessed blood pressure response to orthostatic stress and vascular endothelial function with brachial artery reactivity testing in 34 FD subjects with afferent autonomic failure and 34 healthy control subjects. RESULTS: Forty-four percent of the afferent autonomic failure subjects had uncontrolled hypertension at supine rest (median systolic blood pressure = 148mm Hg, interquartile range (IQR) = 144-155mm Hg; median diastolic blood pressure = 83mm Hg, IQR = 78-105mm Hg), and 88% had abnormal response to orthostatic stress (median decrease in systolic blood pressure after upright tilt = 48mm Hg, IQR = 29-61mm Hg). Flow-mediated brachial artery reactivity did not differ in subjects with afferent autonomic failure vs. healthy control subjects (median = 6.00%, IQR = 1.86-11.77%; vs. median = 6.27%, IQR = 4.65-9.34%; P = 0.75). In afferent autonomic failure subjects, brachial artery reactivity was not associated with resting blood pressure or the magnitude of orthostatic hypotension but was decreased in association with reduced glomerular filtration rate (r = 0.62; P < 0.001). CONCLUSIONS: Brachial artery reactivity was preserved in subjects with afferent autonomic failure despite the presence of marked blood pressure dysregulation. Comorbid renal dysfunction was associated with reduced brachial artery reactivity. PMID- 25128694 TI - Cardiovascular morbidity and mortality after treatment for ductal carcinoma in situ of the breast. AB - BACKGROUND: Recent concerns about potential overdiagnosis and overtreatment of ductal carcinoma in situ of the breast (DCIS) render evaluation of late effects of treatment, such as cardiovascular disease (CVD), of great importance. We studied cardiovascular morbidity and mortality in a large population-based cohort of DCIS patients. METHODS: Data on all incident DCIS case patients in the Netherlands between 1989 and 2004 who were diagnosed before the age of 75 years were obtained (n = 10468). CVD data was acquired through linkage with population based registries. Standardized mortality ratios were calculated by comparing mortality in our cohort with that in the Dutch female population, taking into account person-years of observation. Within-cohort comparisons were based on multivariable competing-risk regression. RESULTS: Compared with the general population, 5-year survivors of DCIS had a similar risk of dying due to any cause (standardized mortality ratio [SMR] = 1.04; 95% confidence interval [CI] = 0.97 to 1.11) but a lower risk of dying of CVD (SMR = 0.77; 95% CI = 0.67 to 0.89). No difference in CVD risk was found when comparing 5-year survivors treated with radiotherapy with those treated with surgery only. Left-sided vs right-sided radiotherapy also did not increase this risk (hazard ratio [HR] = 0.94; 95% CI = 0.67 to 1.32). In a subgroup analysis of all DCIS patients diagnosed between 1997 and 2005, we were able to account for history of CVD and did not observe a risk difference between treatment groups (left-sided vs right-sided radiotherapy: HR = 0.94; 95% CI = 0.68 to 1.29). CONCLUSIONS: After a median follow-up of 10 years, we did not find an increased risk for cardiovascular morbidity or mortality after radiotherapy for DCIS when comparing surgery and radiotherapy vs surgery only, nor when comparing radiotherapy for left-sided vs right-sided DCIS. Compared with the general population, DCIS patients have a decreased risk of cardiovascular death, independent of treatment. PMID- 25128696 TI - Getting to the heart of the matter. PMID- 25128697 TI - Natural populations of Spodoptera exigua are infected by multiple viruses that are transmitted to their offspring. AB - Sublethal infections by baculoviruses (Baculoviridae) are believed to be common in Lepidoptera, including Spodoptera exigua. In addition, novel RNA viruses of the family Iflaviridae have been recently identified in a laboratory population of S. exigua (S. exigua iflavirus-1: SeIV-1; S. exigua iflavirus-2: SeIV-2) that showed no overt signs of disease. We determined the prevalence of these viruses in wild populations and the prevalence of co-infection by the different viruses in shared hosts. Infection by S. exigua multiple nucleopolyhedrovirus (SeMNPV) and iflaviruses in S. exigua adults (N=130) from horticultural greenhouses in southern Spain was determined using qPCR and RT-PCR based techniques respectively. The offspring of these insects (N=200) was reared under laboratory conditions and analyzed to determine virus transmission. Overall, 54% of field caught adults were infected by SeMNPV, 13.1% were infected by SeIV-1 and 7.7% were infected by SeIV-2. Multiple infections were also detected, with 8.4% of individuals harboring SeMNPV and one of the iflaviruses, whereas 2.3% of adults were infected by all three viruses. All the viruses were transmitted to offspring independently of whether the parental female harbored covert infections or not. Analysis of laboratory-reared insects in the adult stage revealed that SeIV-1 was significantly more prevalent than SeMNPV or SeIV-2, suggesting high transmissibility of SeIV-1. Mixed infection involving three viruses was identified in 6.5% of laboratory-reared offspring. We conclude that interspecific interactions between these viruses in co-infected individuals are to be likely frequent, both in the field, following applications of SeMNPV-based insecticides, or in laboratory colonies used for SeMNPV mass production. PMID- 25128695 TI - Hyperthermia inhibits recombination repair of gemcitabine-stalled replication forks. AB - BACKGROUND: Gemcitabine is a potent nucleoside analogue against solid tumors, but development of drug resistance is a substantial problem. Removal of gemcitabine incorporated into DNA by repair mechanisms may contribute to resistance in chemo refractory solid tumors. Human hepatocellular carcinoma (HCC) is usually very chemoresistant to gemcitabine. METHODS: We treated HCC in vitro and in vivo (orthotopic murine model with human Hep3B or HepG2 xenografts, 7-10 CB17SCID mice per group) with gemcitabine. The role of homologous recombination repair proteins in repairing stalled replication forks was evaluated with hyperthermia exposure and cell-cycle analysis. The Student t-test was used for two-sample comparisons. Multiple group data were analyzed using one-way analysis of variance. All statistical tests were two-sided. RESULTS: We demonstrated that Mre11-mediated homologous recombination repair of gemcitabine-stalled replication forks is crucial to survival of HCC cells. Furthermore, we demonstrated inhibition of Mre11 by an exonuclease inhibitor or concomitant hyperthermia. In orthotopic murine models of chemoresistant HCC, the Hep3B tumor mass with radiofrequency plus gemcitabine treatment (mean +/- SD, 180+/-91mg) was statistically significantly smaller compared with gemcitabine alone (661+/-419mg, P = .0063). CONCLUSIONS: This study provides mechanistic understanding of homologous recombination inhibiting-strategies, such as noninvasive radiofrequency field induced hyperthermia, to overcome resistance to gemcitabine in refractory human solid tumors. PMID- 25128698 TI - Effect of gamma-cyclodextrin on solubilization and complexation of irbesartan: influence of pH and excipients. AB - In effort to prepare an eye drop formulation of irbesartan, the effect of gamma cyclodextrin complexation on irbesartan solubilization in aqueous solutions was investigated. The optimum cyclodextrin concentration for formation of irbesartan/cyclodextrin inclusion complex was found to be 10% (w/v) and the solubility of ionized irbesartan/gamma-cyclodextrin complex (at pH 7.2) was shown to be three fold greater than that of the unionized complex (at pH 4.3). The irbesartan flux through semipermeable membranes increased with increasing gamma cyclodextrin concentration at both pH values. However, the ionized complex displayed decrease in the drug permeation coefficient with increasing cyclodextrin concentration. The effect of four pharmaceutical excipients on the cyclodextrin solubilization was investigated. EDTA, hydroxypropyl methylcellulose, and tyloxapol increased complexation efficiency of gamma cyclodextrin while benzalkonium chloride had negligible effect. The largest solubilization was observed in the eye drop vehicle that contained all four excipients in addition to gamma-cyclodextrin. Dynamic light scattering measurements disclosed that excipients had impact on size of complex aggregates and consequently on the drug flux through the semipermeable membranes. Complex of irbesartan/gamma-cyclodextrin was characterized by FT-IR, (1)H NMR, XRPD, and TEM techniques. PMID- 25128699 TI - Impaired Src signaling and post-synaptic actin polymerization in Alzheimer's disease mice hippocampus--linking NMDA receptors and the reelin pathway. AB - Early cognitive deficits in Alzheimer's disease (AD) have been related to deregulation of N-methyl-d-aspartate receptors (NMDARs) and synaptic dysfunction in response to amyloid-beta peptide. NMDAR anchorage to post-synaptic membrane depends in part on Src kinase, which is also implicated in NMDAR activation and actin cytoskeleton stabilization, two processes relevant for normal synaptic function. In this study we analyzed the changes in GluN2B subunit phosphorylation and the levels of proteins involved in Src related signaling pathways linking the Tyr kinase to actin cytoskeleton polymerization, namely reelin, disabled-1 (Dab1) and cortactin, in hippocampal and cortical homogenates obtained from the triple transgenic mouse model of AD (3xTg-AD) that shows progression of pathology as a function of age versus age-matched wild-type mice. Moreover, we evaluated regional post-synaptic actin polymerization using phalloidin labeling in hippocampal slices. Young (3month-old) 3xTg-AD male mice hippocampus exhibited decreased GluN2B Tyr1472 phosphorylation and reduced Src activity. In the cortex, decreased Src activity correlated with reduced levels of reelin and Dab1, implicating changes in the reelin pathway. We also observed diminished phosphorylated Dab1 and cortactin protein levels in the hippocampus and cortex of young 3xTg-AD male mice. Concordantly with the recognized role of these proteins in actin stabilization, we detected a significant decrease in post-synaptic F actin in 3month-old 3xTg-AD male CA1 and CA3 hippocampal regions. These data suggest deregulated Src-dependent signaling pathways involving GluN2B-composed NMDARs and post-synaptic actin cytoskeleton depolymerization in the hippocampus in early stages of AD. PMID- 25128700 TI - Methoxetamine--a novel recreational drug with potent hallucinogenic properties. AB - Methoxetamine is one of the constantly growing group of novel psychoactive substances that has emerged in recent years. The compound belongs to the arylcyclohexylamine class, which is used for its recreational and psychedelic effects. Methoxetamine is a structural analogue of ketamine, with a much longer duration of action and intensity of effects, and has been extensively advertised as its 'legal' and 'bladder friendly' alternative. This review surveys the current state of knowledge regarding the metabolism, pharmacology, prevalence and pattern of methoxetamine use, and analytical methods of its detection. Consumption of methoxetamine bears a significant health risk and may even lead to fatal intoxication. A significant amount of research is still needed in order to fully quantify the short- and long-term effects of methoxetamine and its interaction with other drugs of abuse. PMID- 25128701 TI - Actions of methyl-, propyl- and butylparaben on estrogen receptor-alpha and -beta and the progesterone receptor in MCF-7 cancer cells and non-cancerous MCF-10A cells. AB - Numerous studies have shown that widely used parabens possess estrogenic properties. In the present study, we examined the effects of methyl-, propyl- and butylparaben on the mRNA and protein expression of estrogen receptor (ER)-alpha (ESR1) and -beta (ESR2) and the progesterone receptor (PGR). Human MCF-7 breast cancer cells and MCF-10A non-transformed breast epithelial cells were exposed to parabens at a concentration of 20nM; 17beta-estradiol at a concentration of 10nM, was used as a positive control. Both propyl- and butylparaben stimulated PGR mRNA expression in MCF-7 cells, whereas methyl- and propylparaben PGR protein expression. In MCF-10A cells, butyl- and propylparaben increased only PGR mRNA expression. All parabens increased ESR1 gene and protein expression in MCF-7 and with the exception of butylparaben in MCF-10A cells. All parabens significantly increased ESR2 mRNA and protein expression in MCF-7 cells, but in MCF-10A cells only ESR2 protein expression. In summary, by virtue of their stimulatory action on the expression of ESR1, ESR2 and PGR in cancer cells, parabens can be viewed as potential contributors to breast cancer progression. Extension, the actions of these parabens on the expression of ERs and PGR in non-cancerous cells point to possible actions on breast cancer initiation. PMID- 25128702 TI - Long-term effect of mass chemotherapy, transmission and risk factors for Schistosoma mansoni infection in very low endemic communities of Venezuela. AB - The prevalence of Schistosoma mansoni infection in Venezuela has changed from high to low due mostly to successful control activities, including mass chemotherapy and molluscicide applications. This study examined the impact of mass chemotherapy on S. mansoni transmission and risk factors for infection 12 years after administration of praziquantel in Venezuela. Two relatively isolated rural communities were studied, one with snail control (Manuare) and the second without (Los Naranjos). A cross-sectional survey of randomly selected households included 226 (Manuare) and 192 (Los Naranjos) consenting participants. S. mansoni prevalence was determined using a combination of coprological (Kato-Katz) and serological (circumoval precipitin test, alkaline phosphatase immunoassay and Western blot) tests. Data on epidemiological and socioeconomic risk factors were obtained through individual structured interviews. Univariate analysis and multivariate logistic regression models identified independent risk factors for infection. Water sites were examined for the presence of Biomphalaria glabrata snails. Only one participant was positive by coprology. The overall prevalences according to the combined tests were 32.7% in Manuare and 26.6% in Los Naranjos. Lower prevalences (12.7% in Manuare and 13.2% in Los Naranjos) were found in children <12 years of age representing those born after mass chemotherapy. Social demographic variables associated with infection in both communities were older age (>25 years), contact with specific water sites, and being a farmer/non specialised worker. Mass treatment with praziquantel applied once to endemic communities led to an important and long-lasting sustained reduction of S. mansoni infections independent of the application of snail control. A degree of low active transmission of S. mansoni persisted in the treated areas which was associated with similar factors in both communities. PMID- 25128703 TI - An ultra-sensitive assay targeting the circulating anodic antigen for the diagnosis of Schistosoma japonicum in a low-endemic area, People's Republic of China. AB - The downward trend in prevalence and intensity of Schistosoma japonicum infection in the People's Republic of China (P.R. China) has reached a level where accurate methods are required for monitoring the national schistosomiasis control programme and to verify whether transmission has been interrupted. We have assessed the prevalence of active S. japonicum infection by use of an up converting phosphor lateral-flow (UCP-LF) assay for determination of circulating anodic antigens (CAA) in urine and serum, and compared the findings with those of the Kato-Katz technique for egg detection in stool and an immunohaemagglutination assay (IHA) for specific antibodies in serum. The study was carried out in three villages located in a remaining S. japonicum-endemic area in P.R. China. Overall, 423 individuals were investigated by Kato-Katz, 395 by IHA, 371 with the UCP-LF CAA assay adapted for urine and 178 with the UCP-LF CAA assay applied on serum. The IHA showed the highest number of positive results (n=107, 27.1%). The UCP-LF CAA urine assay detected 36 CAA positives (9.7%) and the serum-based CAA assay 21 positives (11.8%). The Kato-Katz technique revealed only six positive stool samples (1.4%). Among those 166 individuals with complete data records, sensitivities of the different assays were determined versus a combined 'gold' standard, showing the highest sensitivity for the urine CAA assay (93%), followed by the serum CAA (73%) and IHA (53%), whilst triplicate Kato-Katz thick smears had a very low sensitivity (13%). Serum CAA concentrations were about 10-fold higher than in urine and were significantly correlated. Highest prevalences as determined by CAA were found in older age groups (>40 years). Half of the CAA- or egg-positive cases were negative for antibodies by IHA, thereby revealing an important obstacle for the effectiveness of the current schistosomiasis control and elimination efforts. The significantly higher prevalence of active schistosome infections as shown by the urine and serum UCP-LF CAA assays has implications for the national control and elimination programme in P.R. China, particularly in respect to case-finding and intervention strategies. PMID- 25128704 TI - Concomitant inhibition of primary equine bronchial fibroblast proliferation and differentiation by selective beta2-adrenoceptor agonists and dexamethasone. AB - Altered airway cell proliferation plays an important role in the pathogenesis of human bronchial asthma and chronic obstructive pulmonary disease (COPD) as well as the equine recurrent airway obstruction (RAO) with consistent changes, i.e. narrowing the airway wall, explained by proliferation and differentiation of fibroblasts. In permanent cell lines, it has been suggested that beta2 adrenoceptor agonists and glucocorticoids regulate cell proliferation via the beta2-adrenoceptor pathway; indeed, no study was carried out in fresh isolated primary equine bronchial fibroblasts (EBF). We characterized the beta adrenoceptors in EBF, and compared effects of long-acting (clenbuterol) and short acting (salbutamol and isoproterenol) beta2-agonists and dexamethasone on proliferation, differentiation and collagen synthesis. High density (Bmax; 5037+/ 494 sites/cell) of beta2-adrenoceptor subtype was expressed in EBF. beta2 agonists inhibited concentration-dependently EBF proliferation with potency of clenbuterol>salbutamol "isoproterenol which was inhibited by ICI 118.551 and propranolol but not by CGP 20712A. In contrast, dexamethasone alone inhibited less EBF proliferation, but the effect was high when dexamethasone was combined with beta2-agonists. Transforming growth factor-beta1 (TGF-beta1) increased transformation of fibroblasts into myofibroblasts, which was inhibited by clenbuterol and dexamethasone alone and drug combination resulted in high inhibition rate. Collagen synthesis in EBF was rather hampered by dexamethasone than by beta-agonists. Collectively, the expression of beta2-adrenoceptor subtype in EBF and the anti-proliferative effect of clenbuterol suggest that beta2 adrenoceptors are growth inhibitory and anti-fibrotic in EBF. These beta2-agonist effects in EBF were synergistically enhanced by dexamethasone, providing the additive effects of glucocorticoids to counteract airway remodelling and morbidity of asthma and RAO. PMID- 25128706 TI - Regulation of oxidative stress-induced cytotoxic processes of citrinin in the fission yeast Schizosaccharomyces pombe. AB - In this study, the citrinin (CTN)-induced accumulation of reactive oxygen species (ROS) and the regulation of the activities of antioxidant enzymes were investigated in acute toxicity tests in Schizosaccharomyces pombe. 30% of the CTN was accumulated by the cells in 1000 MUM CTN solution. In comparison with the control, exposure of 10(7) cells ml(-1) to 1000 MUM CTN for 60 min at pH = 4.5 induced significantly (p < 1%) elevated levels of peroxides and total ROS, but not of superoxide or hydroxyl radicals, while there was a 3-fold increase in the concentration of glutathione. ROS-induced adaptation processes at cell and molecular levels via activation of the redox-sensitive transcription factors Pap1 and (in part) Atf1 resulted in significantly increased specific activities of glutathione peroxidases, glucose-6-phosphate dehydrogenase and glutathione S transferase and in decreased levels of catalase and glutathione reductase, but no changes were detected in the activities of superoxide dismutases. This treatment caused a G2/M cell cycle arrest and elevated the number of fragmented nuclei, which is one of the markers of apoptosis. Comparison of these results with those for the positive control, 200 MUM H2O2, suggested that CTN induced a medium level of oxidative stress. PMID- 25128705 TI - Effects of interfering RNA of alpha-1,3-galactosyltransferase and nuclear factor kappa B on cardiac xenotransplantation. AB - BACKGROUND: Both alpha1,3-galactosyltransferase (alpha1,3GT) and nuclear factor kappa B (NF-kappaB) play an important role in the immune response of xenotransplantation. The purpose of this study is to investigate the effect of RNAi of alpha1,3GT and NF-kappaB on xenotransplantation. METHODS: Lentiviral vectors with shRNA focusing on alpha1, 3GT and RelA were constructed. The effect of RNAi on alpha1, 3GT and RelA was examined in vitro and in vivo. Additionally, we established a mouse-to-rat heterotopic cardiac xenotransplantatic model (donor hearts transplanted to the right side of the neck in rat) using a modified cuff technique. The survival time of donor hearts in each group was monitored. The expressions of alpha1, 3GT and RelA mRNA, Galalpha1,3Gal antigen, and RelA protein were detected by RT-PCR, immunofluorescence, and Western blot respectively. The expressions of C3, IgM, IgG, NK, macrophages, ICAM-1 on donor hearts were examined by immunohistochemistry. RESULTS: High titer lentiviral vectors carrying alpha1, 3GT and RelA shRNA plasmids had a high and stable transfection rate on EOMA in vitro. In vivo, heart tissue showed a much stronger GFP expression and significant decrease in target gene mRNA expression and protein expression in shRNA interfering groups (p < 0.01). The survival time of alpha1,3GTi-3 and dual lentiviral vector groups was significantly longer than other groups. The mRNA expression levels of alpha1,3GT and RelA, as well as Galalpha(1,3)Gal and RelA proteins, in alpha1,3GTi-3, RelAi-3, and dual lentiviral vector groups were downregulated and compared to other groups (p < 0.01). The depositions of C3, IgM, IgG in alpha1,3GTi-3 group and dual lentiviral vector group were less than other groups (p < 0.01). The infiltration of NK, macrophages and ICAM-1 in alpha1,3GTi-3 group and dual lentiviral vector group was more than other groups (p < 0.01), but the infiltration of NK, macrophages and ICAM-1 in dual lentiviral vector group was less than alpha1,3GTi-3 group (p < 0.01). CONCLUSIONS: Our results indicate that RNAi technology with lentiviral vectors is an effective method to transmit exogenous genes into living bodies and stably inhibit the expression of target genes. Moreover, siRNA targeting the alpha1,3GT gene was found to control the immune process and obviously prolong the survival time of donors, whereas knocking down NF-kappaB alone showed no differences. However, the RNAi of NF-kappaB can make the infiltration of macrophages and natural killer cells decrease, and the expression of ICAM-1 in the xenografts also decreases, contributing to the restraining of AVR. PMID- 25128707 TI - Differential activation of MAPKs by individual and combined ochratoxin A and citrinin treatments in porcine kidney PK15 cells. AB - The aim of this study was to investigate the underlying mechanisms of OTA and CTN individual and combined toxicity in porcine kidney PK15 cells of proximal tubule origin. Activation and expression of mitogen-activated protein kinases (MAPKs) ERK, JNK and p38 were determined by Western blot analysis. MAPKs were differentially activated by single or dual OTA and CTN treatments. Single OTA and CTN stimulated transient ERK and prolonged JNK activation, while phospho-p38 signal was more persistent after OTA treatment. Mycotoxin mixture provoked significant down-regulation of ERK activation, more prolonged phospho-p38 signal, and two-stage JNK phosphorylation pattern. In order to define the role of particular MAPKs in mycotoxin(s) cytotoxicity, we performed MTT assay with specific MAPKs inhibitors. In both individual and combined treatments JNK and p38 inhibition significantly induced cell survival. When cells were exposed to toxin mixture, inhibition of ERK also promoted cell survival, although to a lesser extent that JNK and p38 inhibition. Next we investigated the association between calcium (Ca(2+)) and MAPKs after OTA and/or CTN treatments, and we employed Ca(2+) chelator BAPTA-AM. We demonstrated that p38 activation was significantly down-regulated in cells treated with CTN alone or OTA + CTN suggesting the role of Ca(2+) in mycotoxin-induced cell death. PMID- 25128708 TI - An alternative micromethod to access the procoagulant activity of Bothrops jararaca venom and the efficacy of antivenom. AB - The assessment of the capacity of antivenoms to neutralize the lethal activity of snake venoms still relies largely on traditional rodent lethality assay (LD50). However, adequately validated in vitro tests should be introduced for assessing antivenom neutralizing capacity in plasma of immunized horses as well as for in process quality control. The dynamic of fibrin formation in recalcified avian plasma samples is extremely slow, when compared to that presented by mammalian plasmas. In this study, we present one new coagulant assay, by performing dose response curve after plotting the clotting time (CT) parameter of the ROTEM profile of recalcified chicken plasma samples (target) against semi-logarithmic doses of Bothrops jararaca venom (agonist), either in absence or in presence of the semi-logarithmic doses of anti-bothropic serum (ABS) (antagonist). The mean coagulant dose 50% (CD50) was defined as the quantity of venom (in MUg) which reduces CT to 900 s, between minimum and maximum responses. The CT induced by 5CD50 of the venom was used as the control for calculating the effective dose (ED) of each batch of ABS. ED was defined as the ABS dose (nanoliters, nL) at which CT induced by one amount of venom corresponding to 5CD50 is displaced to the maximum threshold (1800 s). Five batches of the ABS, previously assayed for their lethality neutralizing activity (ED50) were assayed. The correlation coefficient (r) between both in vitro (ED) and in vivo (ED50) values was 0.87 (p value < 0.05). We propose this micro method as highly sensitive for characterization and quantification of possible procoagulant activity of small doses of snake venoms (nanograms) and for detecting small doses (nanoliters) of specific antibodies against this effect in little volume samples of biological fluids. PMID- 25128709 TI - Improving diffusion-weighted imaging of post-mortem human brains: SSFP at 7 T. AB - Post-mortem diffusion imaging of whole, human brains has potential to provide data for validation or high-resolution anatomical investigations. Previous work has demonstrated improvements in data acquired with diffusion-weighted steady state free precession (DW-SSFP) compared with conventional diffusion-weighted spin echo at 3T. This is due to the ability of DW-SSFP to overcome signal-to noise and diffusion contrast losses brought about by tissue fixation related decreases in T2 and ADC. In this work, data of four post-mortem human brains were acquired at 3T and 7 T, using DW-SSFP with similar effective b-values (b(eff)~5150 s/mm(2)) for inter-field strength comparisons; in addition, DW-SSFP data were acquired at 7 T with higher b(eff) (~8550 s/mm(2)) for intra-field strength comparisons. Results demonstrate that both datasets acquired at 7 T had higher SNR and diffusion contrast than data acquired at 3T, and data acquired at higher b(eff) had improved diffusion contrast than at lower b(eff) at 7 T. These results translate to improved estimates of secondary fiber orientations leading to higher fidelity tractography results compared with data acquired at 3T. Specifically, tractography streamlines of cortical projections originating from the corpus callosum, corticospinal tract, and superior longitudinal fasciculus were more successful at crossing the centrum semiovale and projected closer to the cortex. Results suggest that DW-SSFP at 7 T is a preferential method for acquiring diffusion-weighted data of post-mortem human brain, specifically where the primary region of interest involves crossing white matter tracts. PMID- 25128710 TI - The influence of stimulus format on drawing--a functional imaging study of decision making in portrait drawing. AB - To copy a natural visual image as a line drawing, visual identification and extraction of features in the image must be guided by top-down decisions, and is usually influenced by prior knowledge. In parallel with other behavioral studies testing the relationship between eye and hand movements when drawing, we report here a functional brain imaging study in which we compared drawing of faces and abstract objects: the former can be strongly guided by prior knowledge, the latter less so. To manipulate the difficulty in extracting features to be drawn, each original image was presented in four formats including high contrast line drawings and silhouettes, and as high and low contrast photographic images. We confirmed the detailed eye-hand interaction measures reported in our other behavioral studies by using in-scanner eye-tracking and recording of pen movements with a touch screen. We also show that the brain activation pattern reflects the changes in presentation formats. In particular, by identifying the ventral and lateral occipital areas that were more highly activated during drawing of faces than abstract objects, we found a systematic increase in differential activation for the face-drawing condition, as the presentation format made the decisions more challenging. This study therefore supports theoretical models of how prior knowledge may influence perception in untrained participants, and lead to experience-driven perceptual modulation by trained artists. PMID- 25128711 TI - Emotional speech synchronizes brains across listeners and engages large-scale dynamic brain networks. AB - Speech provides a powerful means for sharing emotions. Here we implement novel intersubject phase synchronization and whole-brain dynamic connectivity measures to show that networks of brain areas become synchronized across participants who are listening to emotional episodes in spoken narratives. Twenty participants' hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI) while they listened to 45-s narratives describing unpleasant, neutral, and pleasant events spoken in neutral voice. After scanning, participants listened to the narratives again and rated continuously their feelings of pleasantness-unpleasantness (valence) and of arousal-calmness. Instantaneous intersubject phase synchronization (ISPS) measures were computed to derive both multi-subject voxel-wise similarity measures of hemodynamic activity and inter-area functional dynamic connectivity (seed-based phase synchronization, SBPS). Valence and arousal time series were subsequently used to predict the ISPS and SBPS time series. High arousal was associated with increased ISPS in the auditory cortices and in Broca's area, and negative valence was associated with enhanced ISPS in the thalamus, anterior cingulate, lateral prefrontal, and orbitofrontal cortices. Negative valence affected functional connectivity of fronto-parietal, limbic (insula, cingulum) and fronto-opercular circuitries, and positive arousal affected the connectivity of the striatum, amygdala, thalamus, cerebellum, and dorsal frontal cortex. Positive valence and negative arousal had markedly smaller effects. We propose that high arousal synchronizes the listeners' sound-processing and speech-comprehension networks, whereas negative valence synchronizes circuitries supporting emotional and self-referential processing. PMID- 25128712 TI - Circadian modulation of motor-related beta oscillatory responses. AB - Previous electrophysiological investigations have evaluated movement-related beta (14-28 Hz) oscillatory activity in healthy participants. These studies have described an abrupt decrease in beta activity that starts before movement onset, and a sharp increase in beta power that peaks after movement termination. These neural responses have been respectively termed the event-related beta desynchronization or pre-movement beta ERD, and the post-movement beta rebound (PMBR). Previous studies have shown that a variety of movement parameters and demographic factors (e.g., age) modulate the amplitude of these oscillatory responses, and in the current study we evaluated whether the amplitudes follow a biological temporal rhythm (e.g., circadian), as it is known that spontaneous beta levels increase from morning to afternoon in some brain areas. To this end, we used magnetoencephalography (MEG) to evaluate oscillatory activity during a right hand finger-tapping task in four participants who were recorded at three different times (09:00, 12:00, 16:00) on three consecutive days (i.e., 36 total MEG sessions). All MEG data were corrected for head motion and examined in the time-frequency domain using beamforming methods. We found a significant linear increase in beta ERD amplitude from 09:00 to 16:00 h in the left precentral gyrus, left premotor cortices, left supplementary motor area (SMA), and right precentral and postcentral gyri. In contrast, the amplitude of the PMBR was very steady across the day in all brain regions except the left SMA, which exhibited a linear increase from morning to afternoon. Finally, beta levels during the baseline period also increased from 09:00 to 16:00 in most regions of the cortical sensorimotor network. These data show that both the pre-movement beta ERD and spontaneous beta levels strongly increase from morning to afternoon in the motor cortices, which may indicate that the amplitude of the beta ERD response is determined by the spontaneous beta level during the motor planning period. PMID- 25128714 TI - New cholesterol guidelines and the secondary prevention of cardiovascular disease - a commentary on epistemic aspects. AB - The recommendations contained in the 2013 cholesterol guidelines may be described as either with or without a direct empirical clinical trial basis. Recommendations without a direct empirical clinical trial basis tend to be controversial. Recommendations with and without a direct empirical clinical trial basis are mixed in the same text - while at the same time (rightfully) rejecting previous recommendations, also without a direct empirical clinical trial basis. PMID- 25128713 TI - Age-associated changes in rat immune system: lessons learned from experimental autoimmune encephalomyelitis. AB - Aging is associated with the decline in immune response to infectious agents and tumors and increasing risk of autoimmunity, but the incidence of autoimmune diseases does not increase in the elderly. To elucidate the cellular and molecular mechanisms influencing clinical expression of autoimmunity in aged animals, the phenotypic and functional characteristics of mononuclear cells isolated from the spinal cords of 3-month-old (young) and 26-month-old (aged) Dark Agouti rats immunized to induce experimental autoimmune encephalomyelitis (EAE) - the model of multiple sclerosis, the most common autoimmune disease of the central nervous system, were examined. Aged rats were less susceptible to EAE induction, and the neurological and histological picture was milder in those rats which developed the clinically manifested disease. At the peak of the disease, several times fewer mononuclear cells and T lymphocytes were isolated from the spinal cords of aged rats compared with the young ones. The frequency of CD4+ cells among TCRalphabeta+ lymphocytes, as well as that of reactivated CD134(OX40)+ cells within its CD4+ T-lymphocyte subpopulation, was less in spinal cords of aged compared with young rats. Additionally, CD134 surface density on CD4+ lymphocytes was decreased in the spinal cord of aged rats. The changes in CD134 expression most likely reflected in part age-related intrinsic changes in CD4+ lymphocytes as the expression of this molecule was also impaired on in vitro stimulated naive CD4+ splenocytes from aged rats compared with young animals. In addition, greater frequency of CD8+ lymphocytes with regulatory phenotypes could also contribute to impaired CD4+ cell reactivation in aged rats. The increased apoptosis of CD4+ cells from aged rats was consistent with their impaired reactivation and it was accompanied by the greater frequency of CD4+CD11b+CD45(int/high) cells, which are supposed to be actively engaged in apoptotic cell phagocytosis and to have immunoregulatory properties. Compared with young rats, following short-term PMA and ionomycin stimulation in vitro, the frequency of IL-17+ and IFN-gamma+CD4+ T lymphocytes among the spinal cord mononuclear cells from aged rats and the cytokine expression density on a per lymphocyte basis were reduced. Additionally, the increase in the proportion of autoregulatory IL-17+IL-10+ cells on the account of proinflammatory IL-17+IFN gamma+ cells within IL-17+ lymphocytes suggested their lower pathogenic capacity in aged rats. This most likely reflected alterations in the aged rat spinal cord cytokine milieu, which were mirrored in a diminished expression of IL-1beta mRNA followed by an enhanced expression of IL-6 and TGF-beta mRNA. Overall, the study points to age-related changes in T lymphocytes and other cells from the spinal cord infiltrate which could contribute to the decreased susceptibility of aged rats to the induction of EAE. PMID- 25128715 TI - Racial/ethnic disparities in mental health over the first 2 years after traumatic brain injury: a model systems study. AB - OBJECTIVE: To determine whether racial/ethnic disparities occur in depression, anxiety, and satisfaction with life at 1 and 2 years postdischarge. DESIGN: A prospective, longitudinal, multicenter study of individuals with traumatic brain injury (TBI) participating in the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems project. Medical, demographic, and outcome data were obtained from the Model Systems database at baseline, as well as 1 and 2 years postdischarge. SETTING: A total of 16 TBI Model Systems hospitals in the United States. PARTICIPANTS: Individuals with moderate or severe TBI (N=1662) aged 16 years or older consecutively discharged between January 2008 and June 2011 from acute care and comprehensive inpatient rehabilitation at a Model Systems hospital. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item scale, and Satisfaction with Life Scale assessed depression, anxiety, and satisfaction with life at 1 and 2-year follow-ups. RESULTS: After controlling for all possible covariates, hierarchal linear models found that black individuals had elevated depression across the 2 time points relative to white individuals. Asian/Pacific Islanders' depression increased over time in comparison to the decreasing depression in those of Hispanic origin, which was a greater decrease than in white individuals. Black individuals had lower life satisfaction than did white and Hispanic individuals, but only marginally greater anxiety over time than did white individuals and similar levels of anxiety as did Asian/Pacific Islanders and Hispanic individuals. CONCLUSIONS: Mental health trajectories of individuals with TBI differed as a function of race/ethnicity across the first 2 years postdischarge, providing the first longitudinal evidence of racial/ethnic disparities in mental health after TBI during this time period. Further research will be required to understand the complex factors underlying these differences. PMID- 25128716 TI - Development and initial psychometric evaluation of the Mobility Activities Measure for Inpatient Rehabilitation Settings (Mobam-in). AB - OBJECTIVE: To describe the development and the initial psychometric evaluation of a mobility measure for inpatient postacute rehabilitation settings-the Mobility Activities Measure for Inpatient Rehabilitation Settings (Mobam-in). DESIGN: Self report-based psychometric study. SETTING: Postacute rehabilitation unit of a public hospital. PARTICIPANTS: A consecutive sample of inpatients (N=239) receiving postacute rehabilitation care. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We developed a 30-item mobility measure, using the Mobility Activities Measure (Mobam) framework, to assess functioning across 5 mobility activity domains classified within the International Classification of Functioning, Disability and Health. These were (1) changing and maintaining body position involving only sitting and/or lying (4 items); (2) changing and maintaining body position involving standing up (6 items); (3) carrying and moving objects using the hand and shoulder (6 items); (4) handling objects using only the hand and/or forearm (7 items); and (5) walking and moving (7 items). Psychometric analyses were conducted to test assumptions underlying the scaling and scoring of Mobam-in scales, and to test both the reliability and validity. RESULTS: Multitrait scaling and confirmatory factor analyses (with Tucker-Lewis Index median, .99; root mean square error of approximation median, .025) supported the assumption of unidimensionality concerning each domain. Five dimensions appeared to be stable across diverse diagnostic groups (the percentage of items with discriminant validity ranged from 93% to 100%, Cronbach coefficient ranged from .859 to .966). Rasch model (Masters' partial credit) showed that all items could be located along a continuum in each dimension, with goodness-of-fit criteria of infit and outfit mean-square values between 0.6 and 1.4. Test-retest reliability was excellent (intraclass correlation coefficients median, .98). Groups with more severe conditions and lower functional independence scored lower on Mobam-in scales, as hypothesized. CONCLUSIONS: Mobam-in covers 5 dimensions of mobility activities. The Mobam framework is an effective reference for building outcome instruments. PMID- 25128717 TI - Nanoparticle multivalency counterbalances the ligand affinity loss upon PEGylation. AB - The conjugation of receptor ligands to shielded nanoparticles is a widely used strategy to precisely control nanoparticle-cell interactions. However, it is often overlooked that a ligand's affinity can be severely impaired by its attachment to the polyethylene glycol (PEG) chains that are frequently used to protect colloids from serum protein adsorption. Using the model ligand EXP3174, a small-molecule antagonist for the angiotensin II receptor type 1 (AT1R), we investigated the ligand's affinity before and after its PEGylation and when attached to PEGylated nanoparticles. The PEGylated ligand displayed a 580-fold decreased receptor affinity compared to the native ligand. Due to their multivalency, the nanoparticles regained a low nanomolar receptor affinity, which is in the range of the affinity of the native ligand. Moreover, a four orders of magnitude higher concentration of free ligand was required to displace PEGylated nanoparticles carrying EXP3174 from the receptor. On average, one nanoparticle was decorated with 11.2 ligand molecules, which led to a multivalent enhancement factor of 22.5 compared to the monovalent PEGylated ligand. The targeted nanoparticles specifically bound the AT1R and showed no interaction to receptor negative cells. Our study shows that the attachment of a small-molecule ligand to a PEG chain can severely affect its receptor affinity. Concomitantly, when the ligand is tethered to nanoparticles, the immense avidity greatly increases the ligand-receptor interaction. Based on our results, we highly recommend the affinity testing of receptor ligands before and after PEGylation to identify potent molecules for active nanoparticle targeting. PMID- 25128718 TI - Pre-systemic metabolism of orally administered drugs and strategies to overcome it. AB - The oral bioavailability of numerous drugs is not only limited by poor solubility and/or poor membrane permeability as addressed by the biopharmaceutical classification system (BCS) but also by a pre-systemic metabolism taking place to a high extent in the intestine. Enzymes responsible for metabolic reactions in the intestine include cytochromes P450 (CYP450), transferases, peptidases and proteases. Furthermore, in the gut nucleases, lipases as well as glycosidases influence the metabolic pathway of drugs and nutrients. A crucial role is also played by the intestinal microflora able to metabolize a wide broad of pharmaceutical compounds. Strategies to provide a protective effect towards an intestinal pre-systemic metabolism are based on the co-administration of enzyme inhibitor being optimally immobilized on unabsorbable and undegradable polymeric excipients in order to keep them concentrated there where an inhibitory effect is needed. Furthermore, certain polymeric excipients such as polyacrylates exhibit per se enzyme inhibitory properties. In addition, by incorporating drugs in cyclodextrines, in self-emulsifying drug delivery systems (SEDDS) or liposomes a protective effect towards an intestinal enzymatic attack can be achieved. Being aware of the important role of this pre-systemic metabolism by integrating it in the BCS as third dimension and keeping strategies to overcome this enzymatic barrier in mind, the therapeutic efficacy of many orally given drugs can certainly be substantially improved. PMID- 25128719 TI - Resistin: insulin resistance to malignancy. AB - Adipose tissue is recognized as an endocrine organ that secretes bioactive substances known as adipokines. Excess adipose tissue and adipose tissue dysfunction lead to dysregulated adipokine production that can contribute to the development of obesity-related co-morbidities. Among the various adipokines, resistin, which was initially considered as a determinant of the emergence of insulin resistance in obesity, has appeared as an important link between obesity and inflammatory processes. Several experimental and clinical studies have suggested an association between increased resistin levels and severe conditions associated with obesity such as cardiovascular disease and malignancies. In this review, we present the growing body of evidence that human resistin is an inflammatory biomarker and potential mediator of obesity-associated diseases. A common pathway seems to involve the combined alteration of immune and inflammatory processes that favor metabolic disturbances, atherosclerosis and carcinogenesis. The mode of action and the signaling pathways utilized by resistin in its interactions with target cells could involve oxidative and nitrosative stress. Therefore, resistin could function as a key molecule in the complications of obesity development and could potentially be used as a diagnostic and prognostic marker. PMID- 25128720 TI - Effect of interference from hemolysis, icterus and lipemia on routine pediatric clinical chemistry assays. AB - BACKGROUND: Clinical laboratory assays can be affected by interferents like hemoglobin (Hb), lipids and bilirubin. We evaluated the effect of these interferences on pediatric samples for different chemistry assays. Further we established cut-off indices above which these interferences confound sample results. METHODS: Three separate serum pools were spiked with increasing concentrations of hemolysate or intralipid or bilirubin and different analytes were analyzed. The Hemolysis-(H), Lipemia-(T) and Icterus-(I) indices were measured on Vitros 5600. Analytes affected by lipemia were treated with LipoClear (r) and re-analyzed. All the measured analytes were compromised by gross hemolysis (H-Index >1000). RESULTS: Except lipase and magnesium (Mg(++)), all other analytes were affected by moderate (H-Index >250) and significant hemolysis (H-Index >500). Low estradiol levels showed a significant effect at severe icterus (I-Index >20.0). C3, C4, Ceruloplasmin, Haptoglobin, Immunoglobulins (Ig) and Vitamin D were significantly affected by moderate (T-Index >100) and severe (T-Index >500) lipemia. LipoClear (r) treatment significantly attenuated the lipemic interference on the above analytes except for C3, C4, and IgG. CONCLUSIONS: Accurate reporting of pediatric samples for the analytes affected by common interferences will lead to better clinical interpretation. PMID- 25128721 TI - A computational model for exploratory activity of rats with different anxiety levels in elevated plus-maze. AB - The elevated plus-maze is an apparatus widely used to study the level of anxiety in rodents. The maze is plus-shaped, with two enclosed arms and two open arms, and elevated 50cm from the floor. During a test, which usually lasts for 5min, the animal is initially put at the center and is free to move and explore the entire maze. The level of anxiety is measured by variables such as the percentage of time spent and the number of entries in the enclosed arms. High percentage of time spent at and number of entries in the enclosed arms indicate anxiety. Here we propose a computational model of rat behavior in the elevated plus-maze based on an artificial neural network trained by a genetic algorithm. The fitness function of the genetic algorithm is composed of reward (positive) and punishment (negative) terms, which are incremented as the computational agent (virtual rat) moves in the maze. The punishment term is modulated by a parameter that simulates the effects of different drugs. Unlike other computational models, the virtual rat is built independently of prior known experimental data. The exploratory behaviors generated by the model for different simulated pharmacological conditions are in good agreement with data from real rats. PMID- 25128722 TI - Pixel timing correction in time-lapsed calcium imaging using point scanning microscopy. AB - In point scanning imaging, data are acquired by sequentially scanning each pixel of a predetermined area. This way of scanning leads to time delays between pixels, especially for lower scanning speed or large scanned areas. Therefore, experiments are often performed at lower framerates in order to ensure a sufficient signal-to-noise ratio, even though framerates above 30 frames per second are technically feasible. For these framerates, we suggest that it becomes crucial to correct the time delay between image pixels prior to analyses. In this paper, we apply temporal interpolation (or pixel timing correction) for calcium imaging in two-photon microscopy as an example of fluorescence imaging. We present and compare three interpolation methods (linear, Lanczos and cubic B spline). We test these methods on a simulated network of coupled bursting neurons at different framerates. In this network, we introduce a time delay to simulate a scanning by point scanning microscopy. We also assess these methods on actual microscopic calcium imaging movies recorded at usual framerates. Our numerical results suggest that point scanning microscopy imaging introduces statistically significant time delays between image pixels at low frequency. However, we demonstrate that pixel timing correction compensates for these time delays, regardless of the used interpolation method. PMID- 25128723 TI - A technique to measure cold adaptation in freely behaving mice. AB - BACKGROUND: Adaptation to environmental temperature is essential for survival in seasonal areas. The mechanisms of adaptation have been studied in vitro, but it has not been quantified in vivo. NEW METHOD: The extended Cold Plantar Assay (eCPA) cools the entire testing environment. Once the desired environmental temperature has been reached, a separate focal cold stimulus is applied to the hindpaw and the latency to withdrawal is recorded as a proxy for cold sensitivity. RESULTS: Using this technique, we can test the cold responsiveness of freely behaving mice at ambient temperatures ranging from 5 degrees C to 30 degrees C. The responses are consistent and unambiguous, and the environmental temperatures generated are reproducible. We are also able to measure cold responsiveness as animals are in the process of adapting to cold environments. COMPARISON WITH EXISTING METHOD(S): Existing methods, such as the dynamic cold plate and the 2-plate preference assay test how mice respond to cold environments, but cannot assess how the thresholds for response are changed by acclimation in cold environments. Additionally, the eCPA requires very little specialized equipment, can test many mice at the same time on one apparatus, and has an objective readout. CONCLUSIONS: The extended Cold Plantar assay is a significant methodological improvement, allowing the assessment of cold responsiveness in freely behaving mice at a wide range of environmental temperature conditions and during cold adaptation. PMID- 25128725 TI - The mitochondrial genome of Frankliniella intonsa: insights into the evolution of mitochondrial genomes at lower taxonomic levels in Thysanoptera. AB - Thrips is an ideal group for studying the evolution of mitochondrial (mt) genomes in the genus and family due to independent rearrangements within this order. The complete sequence of the mitochondrial DNA (mtDNA) of the flower thrips Frankliniella intonsa has been completed and annotated in this study. The circular genome is 15,215bp in length with an A+T content of 75.9% and contains the typical 37 genes and it has triplicate putative control regions. Nucleotide composition is A+T biased, and the majority of the protein-coding genes present opposite CG skew which is reflected by the nucleotide composition, codon and amino acid usage. Although the known thrips have massive gene rearrangements, it showed no reversal of strand asymmetry. Gene rearrangements have been found in the lower taxonomic levels of thrips. Three tRNA genes were translocated in the genus Frankliniella and eight tRNA genes in the family Thripidae. Although the gene arrangements of mt genomes of all three thrips species differ massively from the ancestral insect, they are all very similar to each other, indicating that there was a large rearrangement somewhere before the most recent common ancestor of these three species and very little genomic evolution or rearrangements after then. The extremely similar sequences among the CRs suggest that they are ongoing concerted evolution. Analyses of the up and downstream sequence of CRs reveal that the CR2 is actually the ancestral CR. The three CRs are in the same spot in each of the three thrips mt genomes which have the identical inverted genes. These characteristics might be obtained from the most recent common ancestor of this three thrips. Above observations suggest that the mt genomes of the three thrips keep a single massive rearrangement from the common ancestor and have low evolutionary rates among them. PMID- 25128724 TI - Automated detection of 50-kHz ultrasonic vocalizations using template matching in XBAT. AB - BACKGROUND: Ultrasonic vocalizations (USVs) have been utilized to infer animals' affective states in multiple research paradigms including animal models of drug abuse, depression, fear or anxiety disorders, Parkinson's disease, and in studying neural substrates of reward processing. Currently, the analysis of USV data is performed manually, and thus is time consuming. NEW METHOD: The goal of the present study was to develop a method for automated USV recognition using a 'template detection' procedure for vocalizations in the 50-kHz range (35-80kHz). The detector is designed to run within XBAT, a MATLAB graphical user interface and extensible bioacoustics tool developed at Cornell University. RESULTS: Results show that this method is capable of detecting >90% of emitted USVs and that time spent analyzing data by experimenters is greatly reduced. COMPARISON WITH EXISTING METHODS: Currently, no viable and publicly available methods exist for the automated detection of USVs. The present method, in combination with the XBAT environment is ideal for the USV community as it allows others to (1) detect USVs within a user-friendly environment, (2) make improvements to the detector and disseminate and (3) develop new tools for analysis within the MATLAB environment. CONCLUSIONS: The present detector provides an open-source, accurate method for the detection of 50-kHz USVs. Ongoing research will extend the current method for use in the 22-kHz frequency range of ultrasonic vocalizations. Moreover, collaborative efforts among USV researchers may enhance the capabilities of the current detector via changes to the templates and the development of new programs for analysis. PMID- 25128726 TI - Analysis of the transcriptome of Marsdenia tenacissima discovers putative polyoxypregnane glycoside biosynthetic genes and genetic markers. AB - Marsdenia tenacissima is a well-known anti-cancer medicinal plant used in traditional Chinese medicine due to bioactive constituents of polyoxypregnane glycosides, such as tenacissosides, marsdenosides and tenacigenosides. Genomic information regarding this plant is very limited, and rare information is available about the biosynthesis of polyoxypregnane glycosides. To facilitate the basic understanding about the polyoxypregnane glycoside biosynthetic pathways, de novo assembling was performed to generate a total of 73,336 contigs and 65,796 unigenes, which represent the first transcriptome of this species. These included 27 unigenes that were involved in steroid biosynthesis and could be related to pregnane backbone biosynthesis. The expression patterns of six unigenes involved in polyoxypregnane biosynthesis were analyzed in leaf and stem tissues by quantitative real time PCR (qRT-PCR) to explore their putative function. Furthermore, a total of 15,295 simple sequence repeats (SSRs) were identified from 11,911 unigenes, of which di-nucleotide motifs were the most abundant. PMID- 25128727 TI - External air compression: A rare cause of blunt esophageal injury, managed by a stent. AB - INTRODUCTION: Blunt esophageal injuries secondary to external air compression of anterior chest and abdomen complicated with esophageal perforation are uncommon events associated with worse outcomes. PRESENTATION OF CASE: We reported a rare case of esophageal perforation following an external air-compression injury along with the relevant review of literatures. The patient presented with chest pain and shortness of breath and was managed with tube thoracostomy, followed by thoracotomy and eventually with temporary endoscopic stenting. DISCUSSION: In such trauma case, the external pressurized air forms a shock wave which usually directed to the hollow viscus. Patients with external air-compression injury presented with chest pain and pneumothorax should be suspected for esophageal perforation. CONCLUSION: High index of suspicion is needed for early diagnosis of esophageal perforation after blunt trauma. Appropriate drainage, antibiotic and temporary endoscopic esophageal stenting may be an optimal approach in selected patients, especially with delayed diagnosis. PMID- 25128728 TI - Idiopathic bilateral antral exostoses: A rare case in maxillary sinus. AB - INTRODUCTION: Exostoses in paranasal sinuses have been reported in the otolaryngology literature, but they have not been described in the dental literature to our knowledge. The aim of this article is to describe an idiopathic and rare case of bilateral exostosis obtained by cone-beam computed tomography. PRESENTATION OF CASE: The case shows a healthy and asymptomatic patient with a different size and form of exostoses in both maxillary sinuses. DISCUSSION: It is difficult to clinically diagnose the antral exostosis due the asymptomatic nature of this condition, unless the approach would be through endoscope. Sometimes this condition is related with nasal irrigants, however in this case the patient asserted not having used nasal irrigation ever; thus, it is impossible to relate this kind of treatment as a principal cause. CONCLUSION: The published data of exostoses in maxillary sinus seem to be limited in the dental literature, and this condition is important to consider in an implant treatment planning. Also, it is important to perform a follow-up of the cases in trying to find the possible causes of exostosis. PMID- 25128729 TI - Recurrent respiratory distress and cardiopulmonary arrest caused by megaoesophagus secondary to achalasia. AB - INTRODUCTION: Respiratory distress and arrest from tracheal compression secondary to megaoesophagus are rare complications of achalasia. We present the case of a man with end-stage achalasia who required oesophagectomy to prevent recurrent life-threatening tracheal compression and respiratory arrest. A literature review is also presented. PRESENTATION OF CASE: A 40-year old man presented with post prandial stridor which resolved spontaneously, later being diagnosed with achalasia. He underwent pneumatic dilatation year later, intended as definitive treatment. Despite intervention, the patient had developed megaoesophagus. One month later he presented with tracheal compression and cardiorespiratory arrest but was successfully resuscitated. He subsequently underwent elective oesophagectomy. DISCUSSION: Over 40 case reports of achalasia presenting with stridor have been published. However, only three cases (all female, age range, 35 79 years old) of cardiac, respiratory or cardiorespiratory arrest have been published. The definitive treatments received by these patients were botulinum toxin injections, open Heller cardiomyotomy with Dor fundoplication and pneumatic dilatation. None of these patients suffered recurrent respiratory distress following definitive treatment. The patient currently reported was unique as he suffered cardiorespiratory arrest following an intended definitive treatment, pneumatic dilatation. As such oesophagectomy was considered the greatest risk reduction intervention. CONCLUSION: Oesophagectomy should be considered for patients with end-stage achalasia and mega-oesophagus causing respiratory compromise to avoid potential fatal complications such as tracheal compression and subsequent respiratory arrest. PMID- 25128730 TI - Can pelvic tilting be ignored in total hip arthroplasty? AB - INTRODUCTION: The orientation of acetabular component is influenced by pelvic tilt, body position and individual variation in pelvic parameters. Most post operative adverse events may be attributed to malposition of the component in the functional position. There is evidence that orientation of the pelvis changes from the supine to standing position. Authors report a case of recurrent dislocation after total hip arthroplasty due to excessive pelvic tilting. PRESENTATION OF CASE A 69-year old female with coxarthrosis had undergone total hip replacement with recurrent dislocation of the hip on bearing weight in spite of using constrained acetabular component. DISCUSSION: Our case report substantiates the influence of pelvic tilt, incurred by a sagittal deformity of spine, on dynamic orientation of the acetabular cup which was positioned in accordance with the anatomic landmarks alone. If the reference is only bony architecture and dynamic positions of the pelvis are not taken into account, improper functional orientation of the acetabular cup can result in sitting and standing positions. These can induce instability even in anatomically appropriately oriented acetabular component. CONCLUSION: The sagittal position of pelvis is a key factor in impingement and dislocation after total hip arthroplasty. Pelvic tilting affects the position of acetabular component in the sagittal plane of the body as compared with its anatomic position in the pelvis. We suggest a preoperative lateral view of spine-pelvis, in upright and supine position for evaluation of a corrective adaptation of the acetabular cup accordingly with pelvic balance. PMID- 25128731 TI - Kidney stem cells in development, regeneration and cancer. AB - The generation of nephrons during development depends on differentiation via a mesenchymal to epithelial transition (MET) of self-renewing, tissue-specific stem cells confined to a specific anatomic niche of the nephrogenic cortex. These cells may transform to generate oncogenic stem cells and drive pediatric renal cancer. Once nephron epithelia are formed the view of post-MET tissue renal growth and maintenance by adult tissue-specific epithelial stem cells becomes controversial. Recently, genetic lineage tracing that followed clonal evolution of single kidney cells showed that the need for new cells is constantly driven by fate-restricted unipotent clonal expansions in varying kidney segments arguing against a multipotent adult stem cell model. Lineage-restriction was similarly maintained in kidney organoids grown in culture. Importantly, kidney cells in which Wnt was activated were traced to give significant clonal progeny indicating a clonogenic hierarchy. In vivo nephron epithelia may be endowed with the capacity akin to that of unipotent epithelial stem/progenitor such that under specific stimuli can clonally expand/self renew by local proliferation of mature differentiated cells. Finding ways to ex vivo preserve and expand the observed in vivo kidney-forming capacity inherent to both the fetal and adult kidneys is crucial for taking renal regenerative medicine forward. Some of the strategies used to achieve this are sorting human fetal nephron stem/progenitor cells, growing adult nephrospheres or reprogramming differentiated kidney cells toward expandable renal progenitors. PMID- 25128732 TI - Patterning the renal vascular bed. AB - The renal vascular bed has a stereotypic architecture that is essential for the kidney's role in excreting metabolic waste and regulating the volume and composition of body fluids. The kidney's excretory functions are dependent on the delivery of the majority of renal blood flow to the glomerular capillaries, which filter plasma removing from it metabolic waste, as well as vast quantities of solutes and fluids. The renal tubules reabsorb from the glomerular filtrate solutes and fluids required for homeostasis, while the post-glomerular capillary beds return these essential substances back into the systemic circulation. Thus, the kidney's regulatory functions are dependent on the close proximity or alignment of the post-glomerular capillary beds with the renal tubules. This review will focus on our current knowledge of the mechanisms controlling the embryonic development of the renal vasculature. An understanding of this process is critical for developing novel therapies to prevent vessel rarefaction and will be essential for engineering renal tissues suitable for restoring kidney function to the ever-increasing population of patients with end stage renal disease. PMID- 25128734 TI - Use of maternal flecainide concentration in management of fetal supraventricular tachycardia: a step in the right direction. PMID- 25128733 TI - Left atrial appendage morphology and thromboembolic risk after catheter ablation for atrial fibrillation. AB - BACKGROUND: In patients with atrial fibrillation (AF), left atrial appendage (LAA) morphology has been suggested to modify risk of thromboembolic events (TEs). OBJECTIVE: In this study, we tested the hypothesis that a TE after AF catheter ablation is associated with LAA characteristics. METHODS: Of 2069 patients included in the Leipzig Heart Center AF Ablation Registry, 15 (0.7%) suffered a TE (excluding events within 30 days) during follow-up (ie, 3.078 patient-years). Those patients were matched for CHA2DS2-VASc criteria with 115 patients without TE, and computed tomography (n = 120) or magnetic resonance imaging (n = 10) data were also compared. LAA volume, morphology (cactus, chicken wing, windsock, and cauliflower), and takeoff (higher/lower) in relation to the adjacent pulmonary vein were determined. RESULTS: After patients were followed for a median period of 24 months, 67% of the patients remained in sinus rhythm. Patients with TE had a higher AF recurrence rate (73% vs 28%; P = .001) and a higher incidence of superior LAA takeoff (ie, higher than that of the left superior pulmonary vein; 80% vs 37%; P = .002), while LAA morphologies and other LAA characteristics were similar between groups. Multivariate Cox regression analysis revealed AF recurrence (hazard ratio 6.2; 95% confidence interval 2.0 19.6; P = .002) and superior LAA takeoff (hazard ratio 4.9; 95% confidence interval 1.4-17.4; P = .014) as TE predictors. There was a negative correlation between heart rate and LAA flow (r = -.22 cm/s per beat/min; P = .016), which was even more pronounced for the superior LAA takeoff (r = -.28 cm/s; P = .045). CONCLUSION: AF recurrence and higher LAA takeoff are associated with thromboembolism after AF ablation, while LAA morphology is not. These results may have an implication for improved postablation management. PMID- 25128735 TI - Generation of physiological and pathological high frequency oscillations: the role of perisomatic inhibition in sharp-wave ripple and interictal spike generation. AB - Sharp-wave-ripple complexes (SWRs) and interictal-spikes are physiological and pathological forms of irregularly occurring transient high activity events in the hippocampal EEG. They share similar features and carry high-frequency oscillations with different spectral features. Recent results reveal similarities and differences in the generation of the two types of transients, and argue that parvalbumin containing basket cells (PVBCs) are crucial in synchronizing neuronal activity in both cases. SWRs are generated in the reciprocally connected network of inhibitory PVBCs, while in the pathological case, synchronous failure of perisomatic inhibition triggers massive pyramidal cell burst firing. While physiological ripple oscillation is primarily the result of phasic perisomatic inhibitory currents, pathological high-frequency ripples are population spikes of partially synchronous, massively bursting, uninhibited pyramidal cells. PMID- 25128736 TI - Knowledge base and neural network approach for protein secondary structure prediction. AB - Protein structure prediction is of great relevance given the abundant genomic and proteomic data generated by the genome sequencing projects. Protein secondary structure prediction is addressed as a sub task in determining the protein tertiary structure and function. In this paper, a novel algorithm, KB-PROSSP-NN, which is a combination of knowledge base and modeling of the exceptions in the knowledge base using neural networks for protein secondary structure prediction (PSSP), is proposed. The knowledge base is derived from a proteomic sequence structure database and consists of the statistics of association between the 5 residue words and corresponding secondary structure. The predicted results obtained using knowledge base are refined with a Backpropogation neural network algorithm. Neural net models the exceptions of the knowledge base. The Q3 accuracy of 90% and 82% is achieved on the RS126 and CB396 test sets respectively which suggest improvement over existing state of art methods. PMID- 25128737 TI - Interactome analyses of Salmonella pathogenicity islands reveal SicA indispensable for virulence. AB - BACKGROUND: Serovars of Salmonella enterica, namely Typhi and Typhimurium, reportedly, are the bacterial pathogens causing systemic infections like gastroenteritis and typhoid fever. To elucidate the role and importance in such infection, the proteins of the Type III secretion system of Salmonella pathogenicity islands and two component signal transduction systems, have been mainly focused. However, the most indispensable of these virulent ones and their hierarchical role has not yet been studied extensively. RESULTS: We have adopted a theoretical approach to build an interactome comprising the proteins from the Salmonella pathogeneicity islands (SPI) and two component signal transduction systems. This interactome was then analyzed by using network parameters like centrality and k-core measures. An initial step to capture the fingerprint of the core network resulted in a set of proteins which are involved in the process of invasion and colonization, thereby becoming more important in the process of infection. These proteins pertained to the Inv, Org, Prg, Sip, Spa, Ssa and Sse operons along with chaperone protein SicA. Amongst them, SicA was figured out to be the most indispensable protein from different network parametric analyses. Subsequently, the gene expression levels of all these theoretically identified important proteins were confirmed by microarray data analysis. Finally, we have proposed a hierarchy of the proteins involved in the total infection process. This theoretical approach is the first of its kind to figure out potential virulence determinants encoded by SPI for therapeutic targets for enteric infection. CONCLUSIONS: A set of responsible virulent proteins was identified and the expression level of their genes was validated by using independent, published microarray data. The result was a targeted set of proteins that could serve as sensitive predictors and form the foundation for a series of trials in the wet lab setting. Understanding these regulatory and virulent proteins would provide insight into conditions which are encountered by this intracellular enteric pathogen during the course of infection. This would further contribute in identifying novel targets for antimicrobial agents. PMID- 25128738 TI - Quantification and geometric analysis of coiling patterns in gastropod shells based on 3D and 2D image data. AB - The morphology of gastropod shells has been a focus of analyses in ecology and evolution. It has recently emerged as an important issue in developmental biology, thanks to recent advancements in molecular biological techniques. The growing tube model is a theoretical morphological model for describing various coiling patterns of molluscan shells, and it is a useful theoretical tool to relate local tissue growth with global shell morphology. However, the growing tube model has rarely been adopted in empirical research owing to the difficulty in estimating the parameters of the model from morphological data. In this article, I solve this problem by developing methods of parameter estimation when (1) 3D Computed Tomography (CT) data are available and (2) only 2D image data (such as photographs) are available. When 3D CT data are available, the parameters can be estimated by fitting an analytical solution of the growing tube model to the data. When only 2D image data are available, we first fit Raup's model to the 2D image data and then convert the parameters of Raup's model to those of the growing tube model. To illustrate the use of these methods, I apply them to data generated by a computer simulation of the model. Both methods work well, except when shells grow without coiling. I also demonstrate the effectiveness of the methods by applying the model to actual 3D CT data and 2D image data of land snails. I conclude that the method proposed in this article can reconstruct the coiling pattern from observed data. PMID- 25128739 TI - Hispolon inhibition of inflammatory apoptosis through reduction of iNOS/NO production via HO-1 induction in macrophages. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Phellinus linteus (Berkeley & Curtis), a well known medical fungus, has long been used as a traditional medicine in Oriental countries to treat various diseases, and hispolon (HIS) is one of its bioactive components. HIS is known to possess potent antineoplastic and antiviral properties; however, its effect on inflammatory apoptosis is still undefined. MATERIALS AND METHODS: RAW264.7 macrophages were incubated with HIS for 30 min followed by LPS, LTA, or PGN stimulation for 12h. The expression of indicated proteins AP-1 and NF-kappaB transcriptional activities was examined by Western blotting using specific antibodies. Levels of NO and ROS were examined by Griess reaction, and DCHF-DA staining via flow cytometric analysis, respectively. AP-1 and NF-kappaB transcriptional activities were detected by luciferase reporter assay. Knockdown of HO-1 protein expression was performed by transfection of macrophages with HO-1 siRNA. Pharmacological inhibitors including ROS scavenger NAC, JNK inhibitor SP600125, NF-kappaB inhibitor BAY117082 were applied for mechanism study. RESULTS: HIS showed concentration-dependent inhibition of LPS, LTA, and PGN-induced iNOS protein expressions and NO production by RAW264.7 macrophages. Accordingly, HIS protected RAW264.7 cells from LPS-, LTA-, and PGN induced apoptosis. Increased HO-1 by HIS was detected at both protein and mRNA levels along with an increase in intracellular peroxide, and this was inhibited by the translational inhibitor, cycloheximide (CHX), the transcriptional inhibitor, actinomycin D (Act D), and the reactive oxygen species scavenger, N acetylcysteine (NAC). A mechanistic study indicated that inhibition of c-Jun N terminal kinase (JNK) protein phosphorylation, and activator protein (AP)-1 and nuclear factor (NF)-kappaB activation were involved in the anti-inflammatory actions of HIS in macrophages. A structure-activity relationship analysis showed that HIS expressed the most potent effect of inhibiting iNOS and apoptosis elicited by LPS, LTA, and PGN with a significant increase in HO-1 protein in macrophages. CONCLUSIONS: Evidence supporting HIS prevention of inflammatory apoptosis via blocking NO production and inducing HO-1 protein expression in macrophages is provided, and the hydroxyl at position C3 is a critical substitution for the anti-inflammatory actions of HIS. PMID- 25128740 TI - Unraveling novel broad-spectrum antibacterial targets in food and waterborne pathogens using comparative genomics and protein interaction network analysis. AB - Food and waterborne diseases are a growing concern in terms of human morbidity and mortality worldwide, even in the 21st century, emphasizing the need for new therapeutic interventions for these diseases. The current study aims at prioritizing broad-spectrum antibacterial targets, present in multiple food and waterborne bacterial pathogens, through a comparative genomics strategy coupled with a protein interaction network analysis. The pathways unique and common to all the pathogens under study (viz., methane metabolism, d-alanine metabolism, peptidoglycan biosynthesis, bacterial secretion system, two-component system, C5 branched dibasic acid metabolism), identified by comparative metabolic pathway analysis, were considered for the analysis. The proteins/enzymes involved in these pathways were prioritized following host non-homology analysis, essentiality analysis, gut flora non-homology analysis and protein interaction network analysis. The analyses revealed a set of promising broad-spectrum antibacterial targets, present in multiple food and waterborne pathogens, which are essential for bacterial survival, non-homologous to host and gut flora, and functionally important in the metabolic network. The identified broad-spectrum candidates, namely, integral membrane protein/virulence factor (MviN), preprotein translocase subunits SecB and SecG, carbon storage regulator (CsrA), and nitrogen regulatory protein P-II 1 (GlnB), contributed by the peptidoglycan pathway, bacterial secretion systems and two-component systems, were also found to be present in a wide range of other disease-causing bacteria. Cytoplasmic proteins SecG, CsrA and GlnB were considered as drug targets, while membrane proteins MviN and SecB were classified as vaccine targets. The identified broad-spectrum targets can aid in the design and development of antibacterial agents not only against food and waterborne pathogens but also against other pathogens. PMID- 25128741 TI - Role of microRNAs in the modulation of diabetic retinopathy. AB - Diabetic retinopathy (DR) is the leading cause of vision loss in the working-age adults. It affects a third of diabetics. Diabetic macular edema, an advanced complication of DR, develops in nearly 7% of diabetic patients. MicroRNAs (miRNAs) are a novel group of non-coding small RNAs that post-transcriptionally control gene expression by promoting either degradation or translational repression of target messenger RNA. They are implicated in a large variety of physiological and pathophysiological processes, including glucose homeostasis, angiogenesis and modulation of inflammatory response. MiRNAs also play a critical role in the pathogenesis of diabetes and the related micro- and macrovascular complications. The purpose of this review is to describe the potential role of miRNAs in diabetes and evaluate their implication in DR. MiRNAs involved in the modulation of glucose metabolism (insulin secretion and sensitivity) and MiRNAs playing a role in the pathogenesis of DR with their potential target genes are reviewed. Understanding MiRNAs implication in DR could be helpful for developing new gain- or loss- of -function strategies in order to establish effective treatments and reduce the rate of visual disability due to progression of retinopathy. PMID- 25128743 TI - Nonalcoholic fatty liver disease: A main driver of insulin resistance or a dangerous liaison? AB - Insulin resistance is one of the key components of the metabolic syndrome and it eventually leads to the development of type 2 diabetes, making it one of the biggest medical problems of modern society. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are tightly associated with insulin resistance. While it is fairly clear that insulin resistance causes hepatic steatosis, it is not known if NAFLD causes insulin resistance. Hepatic inflammation and lipid accumulation are believed to be the main drivers of hepatic insulin resistance in NAFLD. Here we give an overview of the evidence linking hepatic lipid accumulation to the development of insulin resistance, including the accumulation of triacylglycerol and lipid metabolites, such as diacylglycerol and ceramides. In particular, we discuss the role of obesity in this relation by reviewing the current evidence in terms of the reported changes in body weight and/or adipose tissue mass. We further discuss whether the activation or inhibition of inflammatory pathways, Kupffer cells and other immune cells influences the development of insulin resistance. We show that, in contrast to what is commonly believed, neither hepatic steatosis nor hepatic inflammation is sufficient to cause insulin resistance. Many studies show that obesity cannot be ignored as an underlying factor in this relationship and NAFLD is therefore less likely to be one of the main drivers of insulin resistance. PMID- 25128742 TI - Novel role of silent information regulator 1 in acute endothelial cell oxidative stress injury. AB - Silent information regulator 1 (SIRT1), a class III histone deacetylase, retards aging and plays roles in cellular oxidative stress injury (OSI). However, the biological context in which SIRT1 promotes oxidative injury is not fully understood. Here, we show that SIRT1 essentially mediates hydrogen peroxide (H2O2)-induced cytotoxicity in human umbilical vein endothelial cell (HUVEC). In HUVECs, SIRT1 protein expression was significantly increased in a dose-dependent manner after H2O2 treatment, whereas the acetylation levels of the NF-kappaB p65 subunit and p53 were decreased. EX527 (a specific SIRT1 inhibitor) conferred protection to the HUVECs against H2O2, as indicated by an improved cell viability, adhesion, an enhanced migratory ability, a decreased apoptotic index, decreased reactive oxygen species (ROS) production and reductions in several biochemical parameters. Immunofluorescence and Western blot analyses demonstrated that H2O2 treatment up-regulated SIRT1, phosphorylated-JNK (p-JNK), p-p38MAPK, and p-ERK expression. EX527 pretreatment reversed these effects on SIRT1, p-JNK, and p-p38MAPK but further increased the p-ERK levels. Similar results were confirmed in SIRT1 siRNA experiments. In summary, SIRT1 signaling pathway inhibition imparts protection against acute endothelial OSI, and modulation of MAPKs (JNK, p38MAPK, and ERK) may be involved in the protective effect of SIRT1 inhibition. PMID- 25128744 TI - Prognostic value of glomerular filtration changes versus natriuretic response in decompensated heart failure with reduced ejection. AB - BACKGROUND: Glomerular filtration rate (GFR) and natriuretic response to diuretics represent important treatment targets in acute decompensated heart failure (ADHF). METHODS AND RESULTS: Consecutive ADHF patients (n = 50) with ejection fraction <= 45% and clinical signs of volume overload received protocol driven decongestive therapy. Serum creatinine (Cr), cystatin C (CysC), and beta trace protein (betaTP) were measured on admission and three subsequent days of treatment. Worsening renal function (WRF) was defined as a >= 0.3 increase in absolute biomarker levels or >= 20% decrease in estimated GFR. Consecutive 24 hour urinary collections were simultaneously performed to measure Cr clearance and natriuresis. Serum Cr, CysC, and betaTP were strongly correlated at admission (rho = 0.788-0.909) and during decongestive treatment (rho = 0.884-888). Moreover, derived GFR estimates correlated well with Cr clearance (rho = 0.820 0.908). Nevertheless, WRF incidence differed markedly according to Cr- (26%-30%), CysC- (46%-54%), or betaTP-based definitions (31%-48%). WRF by any definition was not associated with all-cause mortality or ADHF readmission, in contrast to stronger natriuresis per loop diuretic dose [hazard ratio 0.20 (95% confidence interval 0.06-0.64); P = .007]. CONCLUSIONS: Serial measurements of CysC/betaTP, compared with serum Cr, more frequently indicate WRF during decongestive treatment in ADHF. However, adverse clinical outcome in such patients might be better predicted by the natriuretic response to diuretic therapy. PMID- 25128746 TI - Survival rates in out-of-hospital cardiac arrest patients transported without prehospital return of spontaneous circulation: an observational cohort study. AB - BACKGROUND: Some Emergency Medical Services currently use just one component of the Universal Termination of Resuscitation (TOR) Guideline, the absence of prehospital return of spontaneous circulation (ROSC), as the single criteria to terminate resuscitation, which may deny transport to potential survivors. OBJECTIVE: This study aimed to report the survival to hospital discharge rate in non-traumatic, adult out-of-hospital cardiac arrest (OHCA) patients transported to hospital without a prehospital ROSC. METHODS: An observational study of OHCA patients without a prehospital ROSC who met the Universal TOR Guideline for transport to hospital with ongoing resuscitation. Multivariable logistic regression was used to determine the association of each variable with survival to hospital discharge. RESULTS: Of 20,207 OHCA treated by EMS, 3374 (16.4%) did not have a prehospital ROSC but met the Universal TOR guideline for transport to hospital with ongoing resuscitation. Of these patients, 122 (3.6%) survived to hospital discharge. Survival to discharge was associated with initial shockable VF/VT rhythms (OR 5.07; 95% CI 2.77-9.30), EMS-witnessed arrests (OR 3.51; 95% CI 1.73-7.15), bystander-witnessed arrests (OR 2.11; 95% CI 1.18-3.77), and public locations (OR 1.57; 95% CI 1.02-2.40). CONCLUSION: In OHCA patients without a prehospital ROSC who met the Universal TOR Guideline for transport with ongoing resuscitation survival rates were above the 1% futility rate. Employing only the lack of ROSC as criteria for termination of resuscitation may miss survivors after OHCA. PMID- 25128745 TI - Prognostic value of elevated serum ceruloplasmin levels in patients with heart failure. AB - BACKGROUND: Ceruloplasmin (Cp) is a copper-binding acute-phase protein that is increased in inflammatory states and deficient in Wilson's disease. Recent studies demonstrate that increased levels of Cp are associated with increased risk of developing heart failure. Our objective was to test the hypothesis that serum Cp provides incremental and independent prediction of survival in stable patients with heart failure. METHODS AND RESULTS: We measured serum Cp levels in 890 patients with stable heart failure undergoing elective cardiac evaluation that included coronary angiography. We examined the role of Cp levels in predicting survival over 5 years of follow-up. Mean Cp level was 26.6 +/- 6.9 mg/dL and demonstrated relatively weak correlation with B-type natriuretic peptide (BNP; r = 0.187; P < .001). Increased Cp levels were associated with increased 5-year all-cause mortality (quartile [Q] 4 vs Q1 hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.4-2.8; P < .001). When controlled for coronary disease traditional risk factors, creatinine clearance, dialysis, body mass index, medications, history of myocardial infarction, BNP, left ventricular ejection fraction (LVEF), heart rate, QRS duration, left bundle branch blockage, and implantable cardioverter-defibrillator placement, higher Cp remained an independent predictor of increased mortality (Q4 vs Q1 HR 1.7, 95% CI 1.1-2.6; P < .05). Model quality was improved with addition of Cp to the aforementioned covariables (net reclassification improvement of 9.3%; P < .001). CONCLUSIONS: Ceruloplasmin is an independent predictor of all-cause mortality in patients with heart failure. Measurement of Cp may help to identify patients at heightened mortality risk. PMID- 25128747 TI - Occurrence of the three major Vibrio species pathogenic for human in seafood products consumed in France using real-time PCR. AB - Vibrio spp. have emerged as a serious threat to human health worldwide. Vibrio parahaemolyticus, Vibrio cholerae and Vibrio vulnificus are of particular concern as they have been linked to gastrointestinal infections and septicemia associated with the consumption of raw or undercooked seafood. We developed hydrolysis probe based real-time PCR systems with an internal amplification control for the detection of these species. We applied these systems to a total of 167 fresh or frozen crustacean, fish and shellfish samples consumed in France. Of them, 34.7% (n=58) were positive for Vibrio. V. parahaemolyticus was the most common, in 31.1% of samples, followed by V. vulnificus in 12.6% and V. cholerae in 0.6%. Furthermore, V. parahaemolyticus and V. vulnificus were present simultaneously in 9.6% of samples. Virulence genes (tdh and trh sequences) were present in 25% of the V. parahaemolyticus-positive samples. The V. cholerae strain detected was non toxigenic. The densities of V. parahaemolyticus and V. cholerae ranged from <10(2) to 10(4)bacteria/g of seafood. All samples positive for V. vulnificus displayed low-level contamination with fewer than 10(2)bacteria/g. Our findings indicate that seafood consumption presents a potential risk to human health in France and highlight the importance of tools for a preventive consumer protection policy. PMID- 25128749 TI - Impaired coronary microvascular and left ventricular diastolic function in patients with inflammatory bowel disease. AB - BACKGROUND AND AIM: Increased incidence of coronary vascular events in patients with inflammatory bowel disease (IBD) is known. However, the association between coronary microvascular function and IBD has not been fully defined. We aimed to investigate whether coronary flow reserve (CFR) and left ventricular diastolic function were impaired in IBD patients. METHODS: Seventy-two patients with IBD (36 patients with ulcerative colitis [UC] and 36 Crohn's disease [CD]) were registered. Each subject was evaluated after a minimum 15-day attack-free period. For the control group, 36 age- and sex-matched healthy volunteers were included into the study. IBD clinical disease activity in UC was assessed by the Truelove Witts Index (TWAS) and in CD by the Crohn's Disease Activity Index (CDAI). In each subject, CFR was measured through transthoracic Doppler echocardiography. RESULTS: Compared to the controls, the CD group and UC group had significantly higher high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate. Baseline diastolic peak flow velocity (DPFV) of the left anterior descending artery (LAD) was significantly higher in the IBD group (24.1+/-3.9 vs. 22. 4+/-2.9, p<0.05), and hyperemic DPFV (56.1+/-12.5 vs. 70.6+/-15.3, p<0.05) and CFR (2.34+/-0.44 vs. 3.14+/-0.54, p<0.05) were significantly lower in the IBD group than in the control group. In stepwise linear regression analysis, hs-CRP and lateral Em/Am ratio were independently correlated with CFR. CONCLUSION: CFR, reflecting coronary microvascular function, is impaired in patients with IBD. CFR and left ventricular diastolic function parameters are well correlated with hs CRP. PMID- 25128748 TI - Effects of intracerebroventricular injections of 5-HT on systemic vascular resistances of conscious rats. AB - The aims of this study were to determine (i) the effects of intracerebroventricular (i.c.v.) injections of 5-hydroxytryptamine (5-HT, 10MUg) on mean arterial blood pressure (MAP), heart rate (HR) and mesenteric (MR), renal (RR) and hindquarter (HQR) vascular resistances of conscious rats, (ii) the central 5-HT receptor subtype which mediates these effects, and (iii) the role of nitric oxide (NO) in the expression of these responses. The i.c.v. injection of 5 HT had minor effects on MAP but produced a decrease in HR (-18+/-4%), which lasted for 20min. The i.c.v. injection of 5-HT elicited marked increases in MR (+50+/-7%) and reductions in HQR (-31+/-3%). These responses occurred promptly and lasted for 25-35min. 5-HT also produced a transient decrease in RR (-26+/-8% at 10min). All of these responses were prevented by the prior i.c.v. injection of the 5-HT1/5-HT2-receptor antagonist, methysergide (10MUg). The intravenous injection of the NO synthesis inhibitor, L-NAME (25MUmol/kg), produced a sustained pressor response, bradycardia and increases in MR, RR and HQR. Subsequent i.c.v. injection of 5-HT produced a minor pressor response (+7+/-2%), bradycardia (-18+/-3%), an increase in MR (+52+/-8%) but no decreases in RR or HQR. This study demonstrates that i.c.v. 5-HT differentially affects peripheral vascular resistances by activation of central 5-HT1/5-HT2-receptors. It appears that L-NAME did not interfere with the central actions of 5-HT as it did not prevent the 5-HT-induced bradycardia or mesenteric vasoconstriction. Since the 5 HT-induced falls in RR and HQR were abolished by L-NAME, it is possible that these responses are mediated by an active neurogenic process involving the release of NO within the vasculature. PMID- 25128751 TI - Assessment of presentation methods for ReFace computerized facial approximations. AB - Facial approximations (whether clay sculptures, sketches, or computer-generated) can be presented to the public in a variety of layouts, but there are currently no clear indicators as to what style of presentation is most effective at eliciting recognition. The primary purpose of this study is to determine which of five presentation methods produces the most favorable recognition results. A secondary goal of the research is to evaluate a new method for assessing the accuracy of facial approximations. Previous studies have evaluated facial approximation effectiveness using standards similar to studies of eyewitness identification in which a single, definitive choice must be made by the research participant. These criteria seem inappropriate given that facial approximation is strictly an investigative tool to help narrow the search for potential matching candidates in the process of identification. Results from the study showed a higher performance for methods utilizing more than one image of the approximation, but which specific method performed best varied among approximation subjects. Also, results for all five presentation methods showed that, when given the opportunity to select more than one approximation, participants were consistently better at identifying the correct approximation as one of a few possible matches to the missing person than they were at singling out the correct approximation. This suggests that facial approximations have perhaps been undervalued as investigative tools in previous research. PMID- 25128752 TI - Cortical modulation of pain: comments on "exacerbation of tonic but not phasic pain by entorhinal cortex lesions". PMID- 25128750 TI - Engineering in vivo gradients of sphingosine-1-phosphate receptor ligands for localized microvascular remodeling and inflammatory cell positioning. AB - Biomaterial-mediated controlled release of soluble signaling molecules is a tissue engineering approach to spatially control processes of inflammation, microvascular remodeling and host cell recruitment, and to generate biochemical gradients in vivo. Lipid mediators, such as sphingosine 1-phosphate (S1P), are recognized for their essential roles in spatial guidance, signaling and highly regulated endogenous gradients. S1P and pharmacological analogs such as FTY720 are therapeutically attractive targets for their critical roles in the trafficking of cells between blood and tissue spaces, both physiologically and pathophysiologically. However, the interaction of locally delivered sphingolipids with the complex metabolic networks controlling the flux of lipid species in inflamed tissue has yet to be elucidated. In this study, complementary in vitro and in vivo approaches are investigated to identify relationships between polymer composition, drug release kinetics, S1P metabolic activity, signaling gradients and spatial positioning of circulating cells around poly(lactic-co-glycolic acid) biomaterials. Results demonstrate that biomaterial-based gradients of S1P are short-lived in the tissue due to degradation by S1P lyase, an enzyme that irreversibly degrades intracellular S1P. On the other hand, in vivo gradients of the more stable compound, FTY720, enhance microvascular remodeling by selectively recruiting an anti-inflammatory subset of monocytes (S1P3(high)) to the biomaterial. Results highlight the need to better understand the endogenous balance of lipid import/export machinery and lipid kinase/phosphatase activity in order to design biomaterial products that spatially control the innate immune environment to maximize regenerative potential. PMID- 25128753 TI - Behavioral characteristics of subthreshold depression. AB - BACKGROUND: This study examines differences in behavioral characteristics among individuals who are not depressed and individuals with subthreshold depression, and depression. METHODS: We conducted structured interviews with 111 undergraduate students, who also completed self-report scales. The participants were divided into a non-depression group, a subthreshold depression group, and a depression group based on results of the structured interview and the BDI-II. RESULTS: There were significant differences in avoidance between depression group and other two groups. Also, for the environmental rewards, there were significant difference between the non-depressed group and the other two groups. LIMITATIONS: The sample of depressed participants was small. The overall sample consisted only undergraduate students. CONCLUSIONS: This study reported that there are different behavioral characteristics among non-depression, subthreshold depression, and depression groups. Whereas depression group is characterized by high frequency of avoidance and low environmental rewards, subthreshold depression group is characterized by only low environmental rewards. PMID- 25128754 TI - Hospital management of self-harm patients and risk of repetition: systematic review and meta-analysis. AB - BACKGROUND: Self-harm is a common reason for hospital presentation; however, evidence to guide clinical management of these patients to reduce their risk of repeat self-harm and suicide is lacking. METHODS: We undertook a systematic review to investigate whether between study differences in reported clinical management of self-harm patients were associated with the risk of repeat self harm and suicide. RESULTS: Altogether 64 prospective studies were identified that described the clinical care of self-harm patients and the incidence of repeat self-harm and suicide. The proportion of a cohort psychosocially assessed was not associated with the recorded incidence of repeat self-harm or suicide; the incidence of repeat self-harm was 16.7% (95% CI 13.8-20.1) in studies in the lowest tertile of assessment levels and 19.0% (95% CI 15.7-23.0) in the highest tertile. There was no association of repeat self-harm with differing levels of hospital admission (n=47 studies) or receiving specialist follow-up (n=12 studies). In studies reporting on levels of hospital admission and suicide (n=5), cohorts where a higher proportion of patients were admitted to a hospital bed reported a lower incidence of subsequent suicide (0.6%, 95% CI 0.5-0.8) compared to cohorts with lower levels of admission (1.9%, 95% CI 1.1-3.2). LIMITATIONS: In some analyses power was limited due to the small number of studies reporting the exposures of interest. Case mix and aspects of care are likely to vary between studies. DISCUSSION: There is little clear evidence to suggest routine aspects of self-harm patient care, including psychosocial assessment, reduce the risk of subsequent suicide and repeat self-harm. PMID- 25128755 TI - A framework for monitoring social process and outcomes in environmental programs. AB - When environmental programs frame their activities as being in the service of human wellbeing, social variables need to be integrated into monitoring and evaluation (M&E) frameworks. This article draws upon ecosystem services theory to develop a framework to guide the M&E of collaborative environmental programs with anticipated social benefits. The framework has six components: program need, program activities, pathway process variables, moderating process variables, outcomes, and program value. Needs are defined in terms of ecosystem services, as well as other human needs that must be addressed to achieve outcomes. The pathway variable relates to the development of natural resource governance capacity in the target community. Moderating processes can be externalities such as the inherent capacity of the natural system to service ecosystem needs, local demand for natural resources, policy or socio-economic drivers. Internal program specific processes relate to program service delivery, targeting and participant responsiveness. Ecological outcomes are expressed in terms of changes in landscape structure and function, which in turn influence ecosystem service provision. Social benefits derived from the program are expressed in terms of the value of the eco-social service to user-specified goals. The article provides suggestions from the literature for identifying indicators and measures for components and component variables, and concludes with an example of how the framework was used to inform the M&E of an adaptive co-management program in western Kenya. PMID- 25128756 TI - Enhanced contrast separation in scanning electron microscopes via a suspended thin sample approach. AB - A suspended-thin-sample (STS) approach for signal selection and contrast separation is developed in scanning electron microscopes with commonly used primary beam energies and traditional detectors. Topography contrast, electron channeling contrast and composition contrast are separated and largely enhanced from suspended thin samples of several hundred nanometers in thickness, which is less than the escape depth of backscattered electrons. This imaging technique enables to detect relatively pure secondary electron and elastic backscattered electron singles, whereas suppress multiple inelastic scattering effects. The provided contrast features are different from those of bulk samples, which are largely mixed with inelastic scattering effects. The STS imaging concept and method could be expected to have more applications in distinguishing materials of nanostructures, multilayers, compounds and composites, as well as in SEM-based electron backscatter diffraction, cathodoluminesence, and x-ray microanalysis. PMID- 25128757 TI - PCSK9 levels in abdominally obese men: association with cardiometabolic risk profile and effects of a one-year lifestyle modification program. AB - OBJECTIVES: Studies performed in rodents have suggested a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in insulin resistance and impaired body fat distribution. Our objective was to examine the relationships between markers of adiposity and insulin resistance and plasma PCSK9 levels in humans. In addition, we explored the effect of a one-year lifestyle modification program on plasma PCSK9 levels in abdominally obese, dyslipidemic men. METHODS: Plasma PCSK9 levels were measured by ELISA in 175 abdominally obese, dyslipidemic sedentary men. Of these abdominally obese men, 117 non-diabetic individuals completed a one year lifestyle modification program aiming at increasing cardiorespiratory fitness levels and improving nutritional quality. RESULTS: We found no association between plasma PCSK9 levels and body mass index, waist circumference, fat and fat-free mass, or visceral and subcutaneous adipose tissue measured by computed tomography. Compared to men with the lowest PCSK9 levels (bottom tertile), those with the highest PCSK9 levels (top tertile) had the most detrimental lipoprotein-lipid profile including lower LDL particle size (253.6 +/ 4.0 vs. 251.6 +/- 4.0 A, p < 0.05) and higher apolipoprotein C-III levels (36.8 +/- 10.6 vs. 32.3 +/- 32.3, p < 0.05). These men were also characterized by higher HOMA-IR indices (6.78 +/- 3.01 vs. 5.54 +/- 2.91, p < 0.05). After one year, study participants lost on average 6.7 +/- 4.6 kg (p < 0.0001). Plasma PCSK9 decreased by 9.2 +/- 53.7 ng/ml (3.8%, p = 0.07). CONCLUSIONS: Plasma PCSK9 levels are not associated with body fat distribution indices, modestly associated with markers of insulin resistance and LDL particle size and are slightly affected by a lifestyle modification program in abdominally obese men. PMID- 25128758 TI - Osteopontin - a multi-modal marker and mediator in atherosclerotic vascular disease. AB - Atherosclerosis is a chronic inflammatory process of the vessel wall with systemic correlates. It is now well established that patients' outcome is tightly linked to atherosclerotic plaque stability, potentially more so than to the mere plaque size. Osteopontin (OPN) is an integrin-binding ligand, N-linked glycoprotein, which was recognized as a significant participant in the atherosclerotic inflammatory milieu. Evidence from several genetic mouse models suggests that OPN is an enhancer of atherosclerosis. This may be mediated by its capacity to enhance inflammation in the atherosclerotic plaque. Interestingly, OPN may also possess potentially protective vascular effects, such as attenuation of vascular calcification. In humans circulating levels of OPN were found to be independently associated with the severity of coronary atherosclerosis. Moreover, several studies report that high plasma OPN levels were associated with increased risk for major adverse cardiac events. This review aims to critically assess current understanding of the role of OPN in the atherosclerotic process, from animal models to clinical practice. Specific focus is given to evaluating whether OPN could serve as a marker for monitoring coronary atherosclerosis severity, and in parallel, assess the evidence for its role as a mediator in the pathogenic pathways leading to atherosclerotic vascular disease. PMID- 25128759 TI - Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and beta-cell regeneration in mice. AB - BACKGROUND & AIMS: Although the cells that contribute to pancreatic regeneration have been widely studied, little is known about the mediators of this process. During tissue regeneration, infiltrating macrophages debride the site of injury and coordinate the repair response. We investigated the role of macrophages in pancreatic regeneration in mice. METHODS: We used a saporin-conjugated antibody against CD11b to reduce the number of macrophages in mice following diphtheria toxin receptor-mediated cell ablation of pancreatic cells, and evaluated the effects on pancreatic regeneration. We analyzed expression patterns of infiltrating macrophages after cell-specific injury or from the pancreas of nonobese diabetic mice. We developed an in vitro culture system to study the ability of macrophages to induce cell-specific regeneration. RESULTS: Depletion of macrophages impaired pancreatic regeneration. Macrophage polarization, as assessed by expression of tumor necrosis factor-alpha, interleukin 6, interleukin 10, and CD206, depended on the type of injury. The signals provided by polarized macrophages promoted lineage-specific generation of acinar or endocrine cells. Macrophage from nonobese diabetic mice failed to provide signals necessary for beta-cell generation. CONCLUSIONS: Macrophages produce cell type-specific signals required for pancreatic regeneration in mice. Additional study of these processes and signals might lead to new approaches for treating type 1 diabetes or pancreatitis. PMID- 25128760 TI - Dual DNA-binding domains shape the interaction of Brh2 with DNA. AB - Brh2, the BRCA2 ortholog in the fungus Ustilago maydis, harbors two different DNA binding domains, one located in the N-terminal region and the other located in the C-terminal region. Here we were interested in comparing the biochemical properties of Brh2 fragments, Brh2(NT) and Brh2(CT), respectively, harboring the two different DNA-binding regions to understand the mechanistic purpose of dual DNA-interaction domains. With oligonucleotide substrates to model different DNA conformations, it was found that the substrate specificity of Brh2(NT) and Brh2(CT) was almost indistinguishable although avidity was different depending on salt concentration. DNA annealing activity inherent in Brh2 was found to be attributable to Brh2(NT). Likewise, activity responsible for a second-end capture reaction modeling a later step in repair of DNA double-strand breaks was found attributable to Brh2(NT). Efficient annealing of DNA strands coated with RPA required full length Brh2 rather than Brh2(NT) suggesting Brh2(CT) contributes to the activity when RPA is present. Brh2(NT) and Brh2(CT) were both found capable of physically interacting with RPA. The results suggest that while the two DNA binding regions of Brh2 appear functionally redundant in certain aspects of DNA repair, they differ in fundamental properties, and likely contribute in different ways to repair processes involving or arising from stalled DNA replication forks. PMID- 25128761 TI - Remarkable induction of UV-signature mutations at the 3'-cytosine of dipyrimidine sites except at 5'-TCG-3' in the UVB-exposed skin epidermis of xeroderma pigmentosum variant model mice. AB - The human POLH gene is responsible for the variant form of xeroderma pigmentosum (XP-V), a genetic disease highly susceptible to cancer on sun-exposed skin areas, and encodes DNA polymerase eta (poleta), which is specialized for translesion DNA synthesis (TLS) of UV-induced DNA photolesions. We constructed poleta-deficient mice transgenic with lacZ mutational reporter genes to study the effect of Polh null mutation (Polh(-/-)) on mutagenesis in the skin after UVB irradiation. UVB induced lacZ mutations with remarkably higher frequency in the Polh(-/-) epidermis and dermis than in the wild-type (Polh(+/+)) and heterozygote. DNA sequences of a hundred lacZ mutants isolated from the epidermis of four UVB exposed Polh(-/-) mice were determined and compared with mutant sequences from irradiated Polh(+)(/)(+) mice. The spectra of the mutations in the two genotypes were both highly UV-specific and dominated by C->T transitions at dipyrimidines, namely UV-signature mutations. However, sequence preferences of the occurrence of UV-signature mutations were quite different between the two genotypes: the mutations occurred at a higher frequency preferentially at the 5'-TCG-3' sequence context than at the other dipyrimidine contexts in the Polh(+/+) epidermis, whereas the mutations were induced remarkably and exclusively at the 3'-cytosine of almost all dipyrimidine contexts with no preference for 5'-TCG-3' in the Polh( /-) epidermis. In addition, in Polh(-/-) mice, a small but remarkable fraction of G->T transversions was also observed exclusively at the 3'-cytosine of dipyrimidine sites, strongly suggesting that these transversions resulted not from oxidative damage but from UV photolesions. These results would reflect the characteristics of the error-prone TLS functioning in the bypass of UV photolesions in the absence of poleta, which would be mediated by mechanisms based on the two-step model of TLS. On the other hand, the deamination model would explain well the mutation spectrum in the Polh(+/+) genotype. PMID- 25128763 TI - Isolation and characterization of plant growth-promoting rhizobacteria and their effects on phytoremediation of petroleum-contaminated saline-alkali soil. AB - This study aimed to isolate promising halotolerant and alkalotolerant plant growth-promoting rhizobacteria and to study their effects on the growth of tall fescue and phytodegradation efficiency in a petroleum-contaminated saline alkaline soil. A total of 115 PGPR strains were isolated from the rhizosphere of tall fescue grown in petroleum-contaminated saline-alkaline soils. Of these, 5 strains indicating 1-aminocyclopropane-l-carboxylic acid deaminase activity>1.0M alpha-KB mg(-1)h(-1) were selected for further studies. The isolate D5A presented the highest plant-growth-promoting activity and was identified as Klebsiella sp. It grew well on the Luria-Bertani medium containing 9% NaCl and at a pH range of 4-10. A pot experiment was then conducted to study the effect of isolates on phytoremediation. The results showed that inoculation of D5A promoted tall fescue growth and enhanced remediation efficiency in petroleum-contaminated saline alkaline soil. PMID- 25128762 TI - Virus-host mucosal interactions during early SIV rectal transmission. AB - To deepen our understanding of early rectal transmission of HIV-1, we studied virus-host interactions in the rectal mucosa using simian immunodeficiency virus (SIV)-Indian rhesus macaque model and mRNA deep sequencing. We found that rectal mucosa actively responded to SIV as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10 dpi. Our results suggest that the failure of the host to contain virus replication at the portal of entry is attributable to both a high-level expression of lymphocyte chemoattractant, proinflammatory and immune activation genes, which can recruit and activate viral susceptible target cells into mucosa; and a high-level expression of SIV accessory genes, which are known to be able to counter and evade host restriction factors and innate immune responses. This study provides new insights into the mechanism of rectal transmission. PMID- 25128764 TI - Removal of CdTe in acidic media by magnetic ion-exchange resin: a potential recycling methodology for cadmium telluride photovoltaic waste. AB - Sulfonated magnetic microspheres (PSt-DVB-SNa MPs) have been successfully prepared as adsorbents via an aqueous suspension polymerization of styrene divinylbenzene and a sulfonation reaction successively. The resulting adsorbents were confirmed by means of Fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope equipped with an energy dispersive spectrometer (SEM-EDS) and vibrating sample magnetometer (VSM). The leaching process of CdTe was optimized, and the removal efficiency of Cd and Te from the leaching solution was investigated. The adsorbents could directly remove all cations of Cd and Te from a highly acidic leaching solution of CdTe. The adsorption process for Cd and Te reached equilibrium in a few minutes and this process highly depended on the dosage of adsorbents and the affinity of sulfonate groups with cations. Because of its good adsorption capacity in strong acidic media, high adsorbing rate, and efficient magnetic separation from the solution, PSt-DVB-SNa MPs is expected to be an ideal material for the recycling of CdTe photovoltaic waste. PMID- 25128765 TI - The lipid profile of brown adipose tissue is sex-specific in mice. AB - Brown adipose tissue (BAT) is a thermogenic organ with a vital function in small mammals and potential as metabolic drug target in humans. By using high resolution LC-tandem-mass spectrometry, we quantified 329 lipid species from 17 (sub)classes and identified the fatty acid composition of all phospholipids from BAT and subcutaneous and gonadal white adipose tissue (WAT) from female and male mice. Phospholipids and free fatty acids were higher in BAT, while DAG and TAG levels were higher in WAT. A set of phospholipids dominated by the residue docosahexaenoic acid, which influences membrane fluidity, showed the highest specificity for BAT. We additionally detected major sex-specific differences between the BAT lipid profiles, while samples from the different WAT depots were comparatively similar. Female BAT contained less triacylglycerol and more phospholipids rich in arachidonic and stearic acid whereas another set of fatty acid residues that included linoleic and palmitic acid prevailed in males. These differences in phospholipid fatty acid composition could greatly affect mitochondrial membranes and other cellular organelles and thereby regulate the function of BAT in a sex-specific manner. PMID- 25128766 TI - Increased oxidative DNA damage and decreased expression of base excision repair proteins in airway epithelial cells of women who cook with biomass fuels. AB - To investigate whether biomass burning causes oxidative DNA damage and alters the expression of DNA base excision repair (BER) proteins in airway cells, sputum samples were collected from 80 premenopausal rural biomass-users and 70 age matched control women who cooked with liquefied petroleum gas. Compared with control the airway cells of biomass-users showed increased DNA damage in alkaline comet assay. Biomass-users showed higher percentage of cells expressing oxidative DNA damage marker 8-oxoguanine and lower percentages of BER proteins OGG1 and APE1 by immunocytochemical staining. Reactive oxygen species (ROS) generation was doubled and level of superoxide dismutase was depleted significantly among biomass-users. The concentrations of particulate matters were higher in biomass using households which positively correlated with ROS generation and negatively with BER proteins expressions. ROS generation was positively correlated with 8 oxoguanine and negatively with BER proteins suggesting cooking with biomass is a risk for genotoxicity among rural women in their child-bearing age. PMID- 25128767 TI - Increased expression and activation of serum- and glucocorticoid-inducible kinase 1 (SGK1) by cadmium in HK-2 renal proximal tubular epithelial cells. AB - In HK-2 cells exposed to cadmium chloride (CdCl2), the level of serum- and glucocorticoid-inducible kinase-1 (SGK1) protein is increased, but the levels of SGK2 and SGK3 proteins are not. Phosphorylation of SGK1 protein is also observed. Treatment with actinomycin D abolished CdCl2-induced elevation of SGK1 mRNA level. Treatment with actinomycin D or cycloheximide suppressed SGK1 protein levels in cells exposed to CdCl2. Treatment with SGK1 inhibitor EMD638683 or knockdown of SGK1 with siRNA suppressed CdCl2-induced phosphorylation of N-Myc downstream-regulated kinase 1 (NDRG1). These results indicate that cadmium induces the transcriptional upregulation of SGK1 expression and regulates NDRG1 in HK-2 cells. PMID- 25128768 TI - Morpho-physiological effects of ibuprofen on Scenedesmus rubescens. AB - The pollution of aquatic bodies by drugs is an emerging environmental problem, because of their extensive use in animal and human context. Ibuprofen, 2-[4-(2 methylpropyl)phenyl]propanoic acid, is the non-steroidal anti-inflammatory drug mainly present both in wastewater and in rivers and lakes in Europe. Since in literature there is little information about the effects of ibuprofen on microalgae, in this paper we presented the results on the effects of this molecule at different concentrations (62.5MUgL(-1), 250MUgL(-1) and 1000MUgL(-1)) on cultures of the freshwater microalga Scenedesmus rubescens (P.J.L. Dangeard) E. Kesslet et al. Ibuprofen effects on the alga were assayed at first through analyses of the growth curve. Moreover, analyses of cell morphology, ultrastructure, and photosynthetic pigments were additionally performed. The first negative effect of the drug was on the microalga growth, suggesting a drug action dose-dependent mechanism type, more evident at the concentration of 1000MUgL(-1) ibuprofen and in the last phase of the growth curve. In support of this, following ibuprofen exposure, the cells exhibited morphological and ultrastructural alterations, mainly consisting in large cytoplasmic inclusions, probably of lipids and/or carotenoids. The decrease of chlorophyll amounts and, on the contrary, the increase of carotenoids were correlated with a stressful condition induced by drug. PMID- 25128769 TI - Arsenic decreases antinociceptive activity of paracetamol: possible involvement of serotonergic and endocannabinoid receptors. AB - We assessed whether repeated arsenic exposure can decrease paracetamol-mediated antinociception by modulating serotonergic and endocannabinoid pathways. Rats were preexposed to elemental arsenic (4ppm) as sodium arsenite through drinking water for 28 days. Next day paracetamol's (400mg/kg, oral) antinociceptive activity was assessed through formalin-induced nociception. Serotonin content and gene expression of 5-HT1A, 5-HT2A and CB1 receptors were evaluated in brainstem and frontal cortex. Arsenic decreased paracetamol-mediated analgesia. Paracetamol, but not arsenic, increased serotonin content in these regions. Arsenic attenuated paracetamol-mediated increase in serotonin level. Paracetamol did not alter 5-HT1A expression, but caused down-regulation of 5-HT2A and up regulation of CB1 receptors. Arsenic down-regulated these receptors. However, paracetamol-mediated down-regulation of 5-HT2A was more pronounced. Arsenic did not modify paracetamol's effect on 5-HT1A expression, but reduced paracetamol mediated down-regulation of 5-HT2A and reversed up-regulation of CB1 receptors. Results suggest arsenic reduced paracetamol-induced analgesia possibly by interfering with pronociceptive 5-HT2A and antinociceptive CB1 receptors. PMID- 25128770 TI - Chemical composition, anti-inflammatory activity and cytotoxic activity of the liposoluble constituents from different parts of Acanthopanax evodiaefolius by the Herbal Blitzkrieg Extractor. AB - The liposoluble constituents of leaves (LCL) and stem barks (LCSB) from Acanthopanax evodiaefolius Franch were extracted by Herbal Blitzkrieg Extractor (HBE), and their chemical composition was analyzed by GC-MS. 18 compounds were identified, representing 71.98% of LCL, while 35 compounds were identified, accounting for 98.28% of the LCSB. Their cytotoxic activity and inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells were tested and the LCL showed significant NO, IL-6 and TNF-alpha inhibition activity. These results provide the scientific basis for looking for new natural anti inflammatory substances and exploiting and developing resources of A. evodiaefolius Franch. PMID- 25128771 TI - Arsenic trioxide exerts a double effect on osteoblast growth in vitro. AB - Arsenic trioxide (ATO) is a promising antitumor agent used to treat acute promyelocytic leukemia (APL) and, recently solid tumor. The present study was designed to evaluate the effect of ATO proliferation of osteoblast that plays very important roles in maintaining the structure integrity and function of bone. Cell survives, apoptosis, collagen, and molecular targets were identified by multiple detecting techniques, including MTT assay, electron microscopy, collagen detecting kit, TUNEL kit, and western blot in hFOB1.19 human osteoblasts cell line. The results showed that low dose of ATO (0.25, 0.5, and 1MUM) remarkably enhanced the viability of cultured osteoblasts in a concentration- and time dependent manner. Intriguingly, a dual effect of high dose of ATO (5, 10, and 20MUM) was also observed showing significant reduction in viability of culture osteoblasts at concentration- and time-dependent fashion. Moreover, low dose of ATO promoted secretion and synthesis of collagen, whereas high dose of ATO induced typical morphological characteristics of apoptosis in osteoblasts. Mechanically, western blot results demonstrated that low dose of ATO dramatically up-regulated TGF-beta1 protein and activated p-AKT proliferative signaling. And, high dose of ATO increased Bax/Bcl-2 ratio in a time-dependent fashion and activated caspase-3 apoptotic signaling. These results demonstrate at the first time that ATO exerts a double effect on osteoblast function depending upon the concentration and provide a clue to rationally use ATO for clinicians to pay more attention to protect bone from the adverse effects of therapeutic dose of ATO during tumor therapy. PMID- 25128772 TI - Protective effect of naringenin against gentamicin-induced nephrotoxicity in rats. AB - The protective effect of naringenin, a flavonoid compound isolated from citrus fruits, was investigated against nephrotoxicity induced by gentamicin (80mgkg( 1)/day, i.p., for eight days) in rats. Naringenin treatment (50mgkg(-1)/day, p.o.) was administered for eight days, starting on the same day of gentamicin administration. Gentamicin caused significant elevations of serum creatinine, and kidney tissue levels of malondialdehyde, nitric oxide, and interleukin-8, and a significant decrease in renal glutathione peroxidase activity. Naringenin treatment significantly ameliorated the changes in the measured biochemical parameters resulted from gentamicin administration. Also, naringenin markedly attenuated the histopathological renal tissue injury observed with gentamicin. Immunohistochemical examinations showed that naringenin significantly reduced the gentamicin-induced expression of kidney injury molecule-1, vascular endothelial growth factor, inducible nitric oxide synthase, and caspase-9, and increased survivin expression in the kidney tissue. It was concluded that naringenin, through its antioxidant and anti-inflammatory effects, may represent a therapeutic option to protect against gentamicin nephrotoxicity. PMID- 25128773 TI - Geochemical and grain-size distribution of radioactive and stable cesium in Fukushima soils: implications for their long-term behavior. AB - Availability and mobility of radioactive cesium, (137)Cs, in soils are crucial for recovery from the accident in the Fukushima Dai-ichi Nuclear Power Plants. In this study we investigated the geochemical and grain-size distribution of (137)Cs in 11 soil samples collected in the eastern area of Fukushima Prefecture after the accident. Sequential extractions were performed to evaluate the distribution of (137)Cs having different geochemical interactions with soil components. The result was further compared with that of the stable cesium, (133)Cs, which had occurred in the soils before the accident. The distribution of (137)Cs in different grain-size fractions was also determined. Radioactive cesium was predominantly found in the extract obtained by strong-acid dissolution and the extraction residue and was more concentrated in silt and clay grains. X-ray diffraction analyses revealed that micaceous minerals as well as kaolin minerals were predominantly dissolved by the strong-acid treatment. Correlation between the fraction of (137)Cs and the content of micaceous minerals in different grain size fractions of soil minerals suggests that micaceous minerals are responsible for the fixation of (137)Cs in the soils. The isotopic ratio of (137)Cs and (133)Cs in the extract by strong-acid dissolution was more than three times smaller than those in the extracts by water, ion exchange, and reductive dissolution. This indicates that the distribution of (137)Cs was not in the steady state in 2 y after the accident due to relatively slow fixation by the soil clay minerals. PMID- 25128774 TI - High (36)Cl/Cl ratios in Chernobyl groundwater. AB - After the explosion of the Chernobyl Nuclear Power Plant in April 1986, contaminated material was buried in shallow trenches within the exclusion zone. A (90)Sr plume was evidenced downgradient of one of these trenches, trench T22. Due to its conservative properties, (36)Cl is investigated here as a potential tracer to determine the maximal extent of the contamination plume from the trench in groundwater. (36)Cl/Cl ratios measured in groundwater, trench soil water and leaf leachates are 1-5 orders of magnitude higher than the theoretical natural (36)Cl/Cl ratio. This contamination occurred after the Chernobyl explosion and currently persists. Trench T22 acts as an obvious modern point source of (36)Cl, however other sources have to be involved to explain such contamination. (36)Cl contamination of groundwater can be explained by dilution of trench soil water by uncontaminated water (rainwater or deep groundwater). With a plume extending further than that of (90)Sr, radionuclide which is impacted by retention and decay processes, (36)Cl can be considered as a suitable tracer of contamination from the trench in groundwater provided that modern release processes of (36)Cl from trench soil are better characterized. PMID- 25128775 TI - Development of a model using the MATLAB System identification toolbox to estimate (222)Rn equilibrium factor from CR-39 based passive measurements. AB - Can and Bare method is a widely used passive method for measuring the equilibrium factor F through the determination of the track density ratio between bare (D) and filtered (Do) detectors. The dimensions of the used diffusion chamber are altering the deposition ratios of Po-isotopes on the chamber walls as well as the ratios of the existing alpha emitters in air. Then the measured filtered track density and therefore the resultant equilibrium factor is changed according to the diffusion chamber dimensions. For this reason, high uncertainty was expected in the measured F using different diffusion chambers. In the present work, F is derived as a function of both track density ratio (D/Do) and the dimensions of the used diffusion chambers (its volume to the total internal surface area; V/A). The accuracy of the derived formula was verified using the black-box modeling technique via the MATLAB System identification toolbox. The results show that the uncertainty of the calculated F by using the derived formula of F (D/Do, V/A) is only 5%. The obtained uncertainty ensures the quality of the derived function to calculate F using diffusion chambers with wide range of dimensions. PMID- 25128776 TI - Total contents of arsenic and associated health risks in edible mushrooms, mushroom supplements and growth substrates from Galicia (NW Spain). AB - The levels of arsenic (As) in the main commercial species of mushrooms present in Galicia, in their growth substrates, and mushroom supplements have been analysed by ICP-MS, with the intention of assessing potential health risks involved with their consumption. The mean concentrations of As in wild and cultivated mushrooms was 0.27mg/kg dw, in mushroom supplements 0.40mg/kg dw, in soils 5.10mg/kg dw, and in growth substrate 0.51mg/kg dw. No significant differences were observed between species, although the species Lactarius deliciosus possessed a slightly more elevated mean concentration (at 0.49mg/kg dw) than the other species investigated. In soils, statistically significant differences (p<0.05) were observed according to geographic origin. Levels in mushroom supplements, although low, were higher than in wild or cultivated mushrooms. Measured arsenic levels were within the normal range in samples analysed in unpolluted areas. Because of the low As concentrations found in fungi and mushroom supplements from Galicia, and considering the relatively small inclusion of these foods in people's diet, it can be concluded that there is no toxicological risk of arsenic associated with the consumption of the species of mushrooms analysed or at the dosages indicated for mushroom supplements. PMID- 25128777 TI - Outcome and surgical management for geriatric traumatic brain injury: analysis of 888 cases registered in the Japan Neurotrauma Data Bank. AB - OBJECTIVE: As the aged population is rapidly growing globally, geriatric traumatic brain injury (TBI) becomes an increasing problem. There are higher mortality and poorer functional outcome in the geriatric TBI population (>=65 years) compared with younger groups despite neurosurgical interventions. Therefore, current treatment priorities and cost-effectiveness should be critically examined. We evaluated the benefit of surgical management in the elderly (>=65 years) after TBI. METHODS: A total of 3194 patients with confirmed TBI were enrolled from 1998 to 2011, in the Japan Neurotrauma Data Bank. Retrospective analysis was conducted from the Japan Neurotrauma Data Bank on 888 (28%) patients (>=65 years) who did and did not undergo surgery. In particular, the effect of low Glasgow coma scale (GCS) (3-5) was compared with outcome with and without surgery. RESULTS: Of all the patients 65 years of age and over, 478 (54%) were given surgical management (craniectomy, craniotomy, or burr-hole evacuation). This group of patients had significantly more favorable outcome at 6 months (18% vs. 7%) and less mortality (62% vs. 81%). However, within this surgical group, patients with initial GCS scores of 3-5 had significantly more unfavorable outcome (96% vs. 79%) and more mortality (87% vs. 57%) compared with those with GCS scores of 6-15. CONCLUSIONS: We confirmed that age is a major determinant of outcome after TBI. In addition, we found that neurosurgical management is associated with the improvement of the prognosis and a decrease in the rate of mortality in geriatric TBI. However, surgical management was not shown to be an effective treatment in elderly patients with GCS scores of 3-5. PMID- 25128778 TI - Evidence for the light hole in GaAs/AlGaAs quantum wells from optically-pumped NMR and Hanle curve measurements. AB - Optically-pumped (69)Ga NMR (OPNMR) and optically-detected measurements of polarized photoluminescence (Hanle curves) show a characteristic feature at the light hole-to-conduction band transition in a GaAs/AlxGa1-xAs multiple quantum well sample. OPNMR data are often depicted as a "profile" of the OPNMR integrated signal intensity plotted versus optical pumping photon energy. What is notable is the inversion of the sign of the measured (69)Ga OPNMR signals when optically pumping this light hole-to-conduction band energy in OPNMR profiles at multiple external magnetic fields (B0=4.7T and 3T) for both sigma(+) and sigma(-) irradiation. Measurements of Hanle curves at B0=0.5T of the same sample exhibit similar phase inversion behavior of the Hanle curves at the photon energy for light hole excitation. The zero-field value of the light-hole state in the quantum well can be predicted for the quantum well structure using the positions of each of these signal-inversion features, and the spin splitting term in the equation for the transition energy yields consistent values at 3 magnetic fields for the excitonic g-factor (g(ex)). This study demonstrates the application of OPNMR and optical measurements of the photoluminescence to detect the light hole transition in semiconductors. PMID- 25128779 TI - Heteronuclear transverse and longitudinal relaxation in AX4 spin systems: application to (15)N relaxations in (15)NH4(+). AB - The equations that describe the time-evolution of transverse and longitudinal (15)N magnetisations in tetrahedral ammonium ions, (15)NH4(+), are derived from the Bloch-Wangsness-Redfield density operator relaxation theory. It is assumed that the relaxation of the spin-states is dominated by (1) the intra-molecular (15)N-(1)H and (1)H-(1)H dipole-dipole interactions and (2) interactions of the ammonium protons with remote spins, which also include the contribution to the relaxations that arise from the exchange of the ammonium protons with the bulk solvent. The dipole-dipole cross-correlated relaxation mechanisms between each of the (15)N-(1)H and (1)H-(1)H interactions are explicitly taken into account in the derivations. An application to (15)N-ammonium bound to a 41kDa domain of the protein DnaK is presented, where a comparison between experiments and simulations show that the ammonium ion rotates rapidly within its binding site with a local correlation time shorter than approximately 1ns. The theoretical framework provided here forms the basis for further investigations of dynamics of AX4 spin systems, with ammonium ions in solution and bound to proteins of particular interest. PMID- 25128780 TI - Neighbourhood availability of alcohol outlets and hazardous alcohol consumption in New Zealand. AB - The socio-spatial arrangement of alcohol retailers is potentially important in understanding the relationship between neighbourhood context and 'excessive' alcohol consumption. This New Zealand study examines whether the availability of alcohol products is associated with individual-level alcohol consumption. Measures capturing the availability of alcohol retailers were calculated for neighbourhoods across the country and then appended to a national health survey. At the national level there was no evidence for an association between hazardous consumption and alcohol outlet access. However, there was evidence of associations with neighbourhood retailing for younger Maori and Pacific peoples males; younger European females; middle-aged European men; and older men. The findings provide evidence that 'alcogenic' environments are associated with excessive drinking in New Zealand, albeit that the associations are restricted to particular vulnerable groups. PMID- 25128781 TI - Modulation of dendritic cell antigen presentation by pathogens, tissue damage and secondary inflammatory signals. AB - Antigen presentation by dendritic cells (DC) is regulated directly by pathogen associated or cell death-associated cues, or indirectly by immunomodulatory molecules produced during infection or tissue damage. DC modulation by direct encounter of pathogen-associated compounds has been thoroughly studied; the effects of molecules associated with cell death are less well characterized; modulation by secondary signals remain poorly understood. In this review we describe recent studies on the role of these three categories of immunomodulatory compounds on DC. We conclude that characterization of the role of secondary immunomodulators is an area in dare need of further study. The outcomes of this endeavor will be new opportunities for the development of better vaccines and compounds applicable to the therapeutic immunomodulation of DC function. PMID- 25128782 TI - Eosinophils as a pharmacological target for the treatment of allergic diseases. AB - Eosinophils are innate immune cells and active players in inflammatory responses. Their activation and increased levels in the blood and at specific sites are associated with parasitic infections and several inflammatory conditions, notably allergic diseases in which eosinophils are considered to be damaging cells. Intervention targeting eosinophils is thought to prevent and/or limit irreversible organ damage and other eosinophil-associated disorders like hypereosinophilic syndromes, some cancers and autoimmune diseases. Several eosinophil-targeted therapeutic agents which block specific steps in eosinophil differentiation, migration and activation have recently been developed, showing encouraging results and new insights into their specific role in allergy. Here, we review some potentially effective drug compounds, their drawbacks and future prospective focusing on allergic diseases. PMID- 25128784 TI - Carvedilol protects the infarcted heart by upregulating miR-133: first evidence that disease state affects beta-adrenergic arrestin-biased signaling? PMID- 25128783 TI - Upregulation of functional Kv11.1 isoform expression by inhibition of intronic polyadenylation with antisense morpholino oligonucleotides. AB - The KCNH2 gene encodes the Kv11.1 potassium channel that conducts the rapidly activating delayed rectifier current in the heart. KCNH2 pre-mRNA undergoes alternative processing; intron 9 splicing leads to the formation of a functional, full-length Kv11.1a isoform, while polyadenylation within intron 9 generates a non-functional, C-terminally truncated Kv11.1a-USO isoform. The relative expression of Kv11.1 isoforms plays an important role in the regulation of Kv11.1 channel function and the pathogenesis of long QT syndrome. In this study, we identified cis-acting elements that are required for KCNH2 intron 9 poly(A) signal activity. Mutation of these elements decreased Kv11.1a-USO expression and increased the expression of Kv11.1a mRNA, protein and channel current. More importantly, blocking these elements by antisense morpholino oligonucleotides shifted the alternative processing of KCNH2 intron 9 from the polyadenylation to the splicing pathway, leading to the predominant production of Kv11.1a and a significant increase in Kv11.1 current. Our findings indicate that the expression of the Kv11.1a isoform can be upregulated by an antisense approach. Antisense inhibition of KCNH2 intronic polyadenylation represents a novel approach to increase Kv11.1 channel function. PMID- 25128785 TI - Different tobacco retrotransposons are specifically modulated by the elicitor cryptogein and reactive oxygen species. AB - Interactions of plant retrotransposons with different steps of biotic and abiotic stress-associated signaling cascades are still poorly understood. We perform here a finely tuned comparison of four tobacco retrotransposons (Tnt1, Tnt2, Queenti, and Tto1) responses to the plant elicitor cryptogein. We demonstrate that basal transcript levels in cell suspensions and plant leaves as well as the activation during the steps of defense signaling events are specific to each retrotransposon. Using antisense NtrbohD lines, we show that NtrbohD-dependent reactive oxygen species (ROS) production might act as negative regulator of retrotransposon activation. PMID- 25128786 TI - Assessment of candidate reference genes for the expression studies with brassinosteroids in Lolium perenne and Triticum aestivum. AB - Quantitative PCR studies need proper reference genes with expression stability exclusively validated under certain experimental conditions. The expression stability of several genes commonly used as references was tested under 24 epibrassinolide (EBR) and temperature treatment. Different statistical approaches (qBase(PLUS), BestKeeper, NormFinder) were used to prepare rankings of expression stability in two species of an economic importance: common wheat (Triticum aestivum) and perennial ryegrass (Lolium perenne). Candidate reference genes were shown to be regulated differentially in these two plant species. The maximum stability values indicated that the expression stability was higher in T. aestivum. Taking into account of all ranks it seems that TBP-1 and UBI in ryegrass and ACT, ADP and EF1A in wheat should be used as reference genes in the brassinosteroids and temperature involving studies. PMID- 25128787 TI - Responses of a rice-field cyanobacterium Anabaena siamensis TISTR-8012 upon exposure to PAR and UV radiation. AB - The effects of PAR and UV radiation and subsequent responses of certain antioxidant enzymatic and non-enzymatic defense systems were studied in a rice field cyanobacterium Anabaena siamensis TISTR 8012. UV radiation resulted in a decline in growth accompanied by a decrease in chlorophyll a and photosynthetic efficiency. Exposure of cells to UV radiation significantly affected the differentiation of vegetative cells into heterocysts or akinetes. UV-B radiation caused the fragmentation of the cyanobacterial filaments conceivably due to the observed oxidative stress. A significant increase of reactive oxygen species in vivo and DNA strand breaks were observed in UV-B exposed cells followed by those under UV-A and PAR radiation, respectively. The UV-induced oxidative damage was alleviated due to an induction of antioxidant enzymatic/non-enzymatic defense systems. In response to UV irradiation, the studied cyanobacterium exhibited a significant increase in antioxidative enzyme activities of superoxide dismutase, catalase and peroxidase. Moreover, the cyanobacterium also synthesized some UV absorbing/screening substances. HPLC coupled with a PDA detector revealed the presence of three compounds with UV-absorption maxima at 326, 331 and 345 nm. The induction of the biosynthesis of these UV-absorbing compounds was found under both PAR and UV radiation, thus suggesting their possible function as an active photoprotectant. PMID- 25128788 TI - Phonological, temporal and spectral processing in vowel length discrimination is impaired in German primary school children with developmental dyslexia. AB - It is still unclear whether phonological processing deficits are the underlying cause of developmental dyslexia, or rather a consequence of basic auditory processing impairments. To avoid methodological confounds, in the current study the same task and stimuli of comparable complexity were used to investigate both phonological and basic auditory (temporal and spectral) processing in dyslexia. German dyslexic children (Grades 3 and 4) were compared to age- and grade-matched controls in a vowel length discrimination task with three experimental conditions: In a phonological condition, natural vowels were used, differing both with respect to temporal and spectral information (in German, vowel length is phonemic, and vowel length differences are characterized by both temporal and spectral information). In a temporal condition, spectral information differentiating between the two vowels of a pair was eliminated, whereas in a spectral condition, temporal differences were removed. As performance measure, the sensitivity index d' was computed. At the group level, dyslexic children's performance was inferior to that of controls for phonological as well as temporal and spectral vowel length discrimination. At an individual level, nearly half of the dyslexic sample was characterized by deficits in all three conditions, but there were also some children showing no deficits at all. These results reveal on the one hand that phonological processing deficits in dyslexia may stem from impairments in processing temporal and spectral information in the speech signal. On the other hand they indicate, however, that not all dyslexic children might be characterized by phonological or auditory processing deficits. PMID- 25128789 TI - Contrasting deficits on executive functions in Chinese delinquent adolescents with attention deficit and hyperactivity disorder symptoms and/or reading disability. AB - Many studies reported high prevalence of reading disability (RD) and attention deficit hyperactivity disorder (ADHD) among delinquent adolescents. Very few have examined their cognitive profile. The present study compared the executive functions (EFs) and severity of delinquency in delinquent adolescents with RD and/or ADHD symptoms (AS). Delinquents with AS (n=29), RD (n=24), comorbidity AS+RD (n=35) were recruited from juvenile institutions along with typically developing controls (n=29) from local schools; all completed EF assessments and self-report questionnaires on delinquency. Results showed that pure AS group exhibited impaired inhibition while the pure RD group was weak in processing speed and visual memory. The comorbidity group showed unique impairments in interference control and significantly higher delinquency severity. The present findings suggest that comorbidity AS+RD may influence delinquency severity. It also provides a more comprehensive picture of the unique EF deficits associated with different groups, allowing for better matching for future identification and intervention programme. PMID- 25128790 TI - Memory failures for everyday tasks in caregivers of children with autism. AB - The stress of caring for a loved one with chronic illness has been linked with impairments in cognitive processes such as attention and problem solving, though few studies have examined the impact on memory. Compromised cognition, in particular, aspects of everyday functioning such as remembering medical instructions and appointments, might affect caregivers' ability to maintain the consistency and quality of care needed by the child. A sample of 31 caregivers of children with autism and 51 parents of neuro-typical children completed an electronic survey assessing their levels of psychological distress and everyday memory. Perceived stress scores were higher in the caregiver group, as were self reported memory failures for everyday tasks. The negative impact of caregiver stress on everyday memory was particularly salient among caregivers experiencing higher perceived levels of stress. These findings have implications for interventions that aim to improve caregivers' cognitive well being through targeting the psychological sequelae associated with the caregiving experience. PMID- 25128793 TI - Explaining prompts children to privilege inductively rich properties. AB - Four experiments with preschool-aged children test the hypothesis that engaging in explanation promotes inductive reasoning on the basis of shared causal properties as opposed to salient (but superficial) perceptual properties. In Experiments 1a and 1b, 3- to 5-year-old children prompted to explain during a causal learning task were more likely to override a tendency to generalize according to perceptual similarity and instead extend an internal feature to an object that shared a causal property. Experiment 2 replicated this effect of explanation in a case of label extension (i.e., categorization). Experiment 3 demonstrated that explanation improves memory for clusters of causally relevant (non-perceptual) features, but impairs memory for superficial (perceptual) features, providing evidence that effects of explanation are selective in scope and apply to memory as well as inference. In sum, our data support the proposal that engaging in explanation influences children's reasoning by privileging inductively rich, causal properties. PMID- 25128792 TI - Is it or isn't it: listeners make rapid use of prosody to infer speaker meanings. AB - A visual world experiment examined the time course for pragmatic inferences derived from visual context and contrastive intonation contours. We used the construction It looks like an X pronounced with either (a) a H(*) pitch accent on the final noun and a low boundary tone, or (b) a contrastive L+H(*) pitch accent and a rising boundary tone, a contour that can support contrastive inference (e.g., It LOOKSL+H*like a zebraL-H%... (but it is not)). When the visual display contained a single related set of contrasting pictures (e.g. a zebra vs. a zebra like animal), effects of LOOKSL+H* emerged prior to the processing of phonemic information from the target noun. The results indicate that the prosodic processing is incremental and guided by contextually-supported expectations. Additional analyses ruled out explanations based on context-independent heuristics that might substitute for online computation of contrast. PMID- 25128791 TI - Administration of the nicotinic acetylcholine receptor agonists ABT-089 and ABT 107 attenuates the reinstatement of nicotine-seeking behavior in rats. AB - Current smoking cessation pharmacotherapies have modest efficacy, and most smokers relapse within the first few days after a quit attempt. Nicotine withdrawal-induced craving and cognitive impairments predict smoking relapse during abstinence and suggest that cognitive-enhancing drugs may prevent relapse. ABT-089 and ABT-107 are subtype-selective nAChR agonists that improve cognitive performance in laboratory animals. However, there are no studies examining the effects of ABT-089 and ABT-107 on nicotine self-administration and the reinstatement of nicotine-seeking behavior, an animal model of relapse in human smokers. The goal of the present study was to determine the effects of the alpha4beta2*/alpha6beta2* nAChR agonist ABT-089 and the alpha7 nAChR agonist ABT 107 on nicotine taking and seeking in rats. The effects of acute ABT-089 and ABT 107 pretreatment on nicotine self-administration and reinstatement were tested in male Sprague Dawley rats. Parallel studies of ABT-089 and ABT-107 on sucrose self administration and reinstatement were tested in separate groups of rats to determine if the effects of these drug treatments generalized to other reinforced behaviors. Nicotine and sucrose self-administration behaviors were not altered following acute administration of ABT-089 (0, 0.12, 1.2 and 12.0mg/kg) or ABT-107 (0, 0.03 and 0.3mg/kg). In contrast, both ABT-089 and ABT-107 pretreatment dose dependently attenuated nicotine reinstatement. These effects were reinforcer specific as no effects of ABT-089 or ABT-107 pretreatment on sucrose seeking were noted. Taken together, these findings suggest that ABT-089 and ABT-107 do not affect nicotine consumption, but may reduce the likelihood that a smoking lapse will lead to relapse. PMID- 25128794 TI - Examining the costs and benefits of inhibition in memory retrieval. AB - Inhibitory control is thought to serve an adaptive function in controlling behavior, with individual differences predicting variation in numerous cognitive functions. However, inhibition is more properly construed as inducing both benefits and costs to performance. Benefits arise at the point when inhibition prevents expression of an unwanted or contextually inappropriate response; costs arise later, when access to the inhibited representation is required by other processes. Here we illustrate how failure to consider both the costs and benefits of inhibition has generated confusion in the literature on individual differences in cognitive control. Using retrieval-induced forgetting as a model case, we illustrate this by showing that changing the way that retrieval-induced forgetting is measured to allow greater expression of the benefits of inhibition together with the costs can reduce and even reverse the theoretically predicted correlation between motor and memory inhibition. Specifically, we show that when the final test in a retrieval-induced forgetting procedure employs item-specific cues (i.e., category-plus-stem cued recall and item-recognition) that better isolate the lingering costs of inhibition, better motor response inhibition (faster stop-signal reaction times) predicts greater retrieval-induced forgetting. In striking contrast, when the final test is less well controlled, allowing both the costs and benefits of inhibition to contribute, motor response inhibition has the opposite relationship with retrieval-induced forgetting. These findings underscore the importance of considering the correlated costs and benefits problem when studying individual differences in inhibitory control. More generally, they suggest that a shared inhibition mechanism may underlie people's ability to control memories and actions. PMID- 25128795 TI - Building phrases in language production: an MEG study of simple composition. AB - Although research on language production has developed detailed maps of the brain basis of single word production in both time and space, little is known about the spatiotemporal dynamics of the processes that combine individual words into larger representations during production. Studying composition in production is challenging due to difficulties both in controlling produced utterances and in measuring the associated brain responses. Here, we circumvent both problems using a minimal composition paradigm combined with the high temporal resolution of magnetoencephalography (MEG). With MEG, we measured the planning stages of simple adjective-noun phrases ('red tree'), matched list controls ('red, blue'), and individual nouns ('tree') and adjectives ('red'), with results indicating combinatorial processing in the ventro-medial prefrontal cortex (vmPFC) and left anterior temporal lobe (LATL), two regions previously implicated for the comprehension of similar phrases. These effects began relatively quickly (~180 ms) after the presentation of a production prompt, suggesting that combination commences with initial lexical access. Further, while in comprehension, vmPFC effects have followed LATL effects, in this production paradigm vmPFC effects occurred mostly in parallel with LATL effects, suggesting that a late process in comprehension is an early process in production. Thus, our results provide a novel neural bridge between psycholinguistic models of comprehension and production that posit functionally similar combinatorial mechanisms operating in reversed order. PMID- 25128796 TI - Perception of tones by infants learning a non-tone language. AB - This article examines the perception of tones by non-tone-language-learning (non tone-learning) infants between 5 and 18 months in a study that reveals infants' initial sensitivity to tonal contrasts, deterioration yet plasticity of tonal sensitivity at the end of the first year, and a perceptual rebound in the second year. Dutch infants in five age groups were tested on their ability to discriminate a tonal contrast of Mandarin Chinese as well as a contracted tonal contrast. Infants are able to discriminate tonal contrasts at 5-6 months, and their tonal sensitivity deteriorates at around 9 months. However, the sensitivity rebound sat 17-18 months. Non-tone-learning infants' tonal perception is elastic, as is shown by the influence of acoustic salience and distributional learning: (1) a salient contrast may remain discriminable throughout infancy whereas a less salient one does not; (2) a bimodal distribution in tonal exposure increases non tone-learning infants' discrimination ability during the trough in sensitivity to tonal contrasts at 11-12 months. These novel findings reveal non-tone-learning infants' U-shaped pattern in tone perception, and display their perceptual flexibility. PMID- 25128797 TI - On predicting others' words: electrophysiological evidence of prediction in speech production. AB - The present study investigated whether lexical processes that occur when we name objects can also be observed when an interaction partner is naming objects. We compared the behavioral and electrophysiological responses of participants performing a conditional go/no-go picture naming task in two different conditions: individually and jointly with a confederate participant. To obtain an index of lexical processing, we manipulated lexical frequency, so that half of the pictures had corresponding names of high-frequency and the remaining half had names of low-frequency. Color cues determined whether participants should respond, whether their task-partner should respond, or whether nobody should respond. Behavioral and ERP results showed that participants engaged in lexical processing when it was their turn to respond. Crucially, ERP results on no-go trials revealed that participants also engaged in lexical processing when it was their partner's turn to act. In addition, ERP results showed increased response inhibition selectively when it was the partner's turn to act. These findings provide evidence for the claim that listeners generate predictions about speakers' utterances by relying on their own action production system. PMID- 25128798 TI - Distributional learning has immediate and long-lasting effects. AB - Evidence of distributional learning, a statistical learning mechanism centered on relative frequency of exposure to different tokens, has mainly come from short term learning and therefore does not ostensibly address the development of important learning processes. The present longitudinal study examines both short- and long-term effects of distributional learning of phonetic categories on non native sound discrimination over a 12-month period. Two groups of listeners were exposed to a two-minute distribution of auditory stimuli in which the most frequently presented tokens either approximated or exaggerated the natural production of the speech sounds, whereas a control group listened to a piece of classical music for the same length of time. Discrimination by listeners in the two distribution groups improved immediately after the short exposure, replicating previous results. Crucially, this improvement was maintained after six and 12 months, demonstrating that distributional learning has long-lasting effects. PMID- 25128799 TI - Alerting enhances attentional bias for salient stimuli: evidence from a global/local processing task. AB - The present study examined the role of alerting in modulating attentional bias to salient events. In a global/local processing task, participants were presented with a large arrow (global level) comprised of smaller arrows (local level) pointing in the same or opposite directions and had to indicate the direction of the large or small arrows in different blocks. Saliency of the global and local levels was manipulated, creating global-salient and local-salient conditions. Alerting signals were presented in half of the trials prior to the target. Results revealed a double dissociation in the effects of alerting on global/local interference effects. In a global salient condition, alerting increased global interference and decreased local interference. In a local salient condition, alerting reduced global interference and increased local interference. We demonstrate that within a single task, alerting can increase and reduce conflict based on perceptual saliency. These findings help to better understand disorders like hemispatial neglect in which both arousal and attention to salient events are impaired. These results also challenge previous theories suggesting that alerting acts to increase conflict interference. We argue that alerting is an adaptive mechanism that diverts attention to salient events, but comes at a cost when selective attention to less salient details is required. PMID- 25128800 TI - In vitro anti-leishmanial efficacy of potato tuber extract (PTEx): leishmanial serine protease(s) as putative target. AB - Leishmaniasis, a neglected tropical disease (NTD) causes major health problems in the tropical and subtropical world. Most of the antileishmanial modern therapies with different formulations of pentavalent antimonials, Miltefosine, Amphotericin B etc. are not satisfactory in recent times due to high toxicity to the host and present rising strain resistance issues. So there is an urgent need to develop new, safe and cost-effective drugs against leishmaniasis. In this regard, bioactive phytocomponents may lead to the discovery of new medicines with appropriate efficiency. The prominent roles played by Leishmania proteases in the virulence of this parasite make them very promising targets for the development of current therapeutics of leishmaniasis. As part of a search for novel drugs, we have evaluated in vitro anti-leishmanial activity of serine protease inhibitor rich fraction (PTEx) obtained from potato tuber. The extract (PTEx) was prepared by sodium bisulfite fractionation and inhibitors were identified by reverse zymography. Inhibition study of PTEx in gelatin-zymogram and spectrophotometric assay using BApNA and BTpNA as substrate reveal its strong inhibitory activity against trypsin as well as serine proteases present in cell lysate of Leishmania donovani infective strain. The in vitro MTT based colorimetric assay as well as ex vivo L. donovani infected macrophages showed reduced parasite viability and intracellular parasite load with IC50 = 312.5 +/- 0.1 MUg/ml and IC50 82.3 +/- 0.2 MUg/ml of PTEx respectively in a concentration dependent manner. This anti leishmanial effect was also preceded by PTEx induced acute formation of ROS and prolonged NO generation. The PTEx has no significant cytotoxic effect on host macrophages. So taken together, these findings indicate that PTEx has promising leishmanicidal effect and thus this study provides a new perspective of natural serine protease inhibitor from potato tuber on the development of new drug against leishmaniasis. PMID- 25128801 TI - The potential of quinoline derivatives for the treatment of Toxoplasma gondii infection. AB - Here we reported our investigation, as part of our drug repositioning effort, on anti-Toxoplasma properties of newly synthesized quinoline compounds. A collection of 4-aminoquinoline and 4-piperazinylquinoline analogs have recently been synthesized for use in cancer chemotherapy. Some analogs were able to outperform chloroquine, a quinoline derivative drug which is commonly used in the treatment of malaria and other parasitic infections. Herein 58 compounds containing one or two quinoline rings were examined for their effectiveness as potential anti Toxoplasma compounds. Of these 58 compounds, 32 were efficient at inhibiting Toxoplasma growth (IC50<100 MUM). Five compounds with single and simple quinoline rings exhibited similar cLogP values of ~2 and IC50 values between 5 and 6 MUM, with one exception of 8-hydroxyquinoline whose IC50 value was 213 nM. The addition of one hydroxyl group at position 8 caused a 40-fold increase in the inhibitory effect of quinoline. A significant improvement in anti-Toxoplasma effect among quinoline derivatives was detected in B11, B12, B23, and B24, whose structures carry two quinoline rings, and their resultant cLogP values are ?7. Among these compounds, B23 was the most effective compound with IC50 value of 425+/-35 nM, and TI value of 4.9. It was also noted that compounds with at least one quinoline ring, displaying anti-Toxoplasma effects were capable of causing the disappearance of the apicoplast, a plastid-like organelle. When treated with quinoline, 8-hydroxyquinoline or B23, 40-45% of the parasites lost their apicoplasts. Our findings recapitulate the properties of quinoline derivatives in diminishing apicoplast. This could aid further investigations of anti-parasitic treatments specific to Apicomplexan. More importantly, B12 and B23 which harbor superior anti-cancer properties than chloroquine, have effective anti-Toxoplasma activity. These compounds therefore have significant potential for future development of chemotherapeutic agents for patients suffering from breast cancers and parasitic infection. PMID- 25128802 TI - Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in humans. AB - The intranasal use of rintatolimod, a specific TLR-3 agonist, combined with trivalent seasonal influenza vaccine generated cross-protection against highly pathogenic H5N1 avian influenza in mice. The purpose of this clinical trial is to assess the safety and impact of rintatolimod on intranasal influenza vaccine in healthy adults. During Stage I of this Phase I/II clinical trial, 12 volunteers were immunized intranasally with 3 doses of FluMist seasonal influenza vaccine on Days 0, 28, and 56 followed by intranasal rintatolimod (50 MUg, 200 MUg, or 500 MUg) 3 days later. Parotid saliva and nasal wash samples were collected at baseline and on Days 25, 53, 84, and 417. The samples were tested for IgA and IgG specific antibodies (Ab) directed against the homologous FluMist viral hemagglutinins (HAs). In addition, viral specific responses against influenza A HAs were tested for IgA Ab cross-reactivity against 3 H5 clades: HA (H5N1) A/Indonesia/5/2005, HA (H5N1) A/Hong Kong/483/97 and HA (H5N1) A/Vietnam/1194/2004, as well as, two H7 strains, HA (H7N9) A/Shanghai/2/2013 and HA (H7N3) A/chicken/Jalisco/CPA1. The combination of the intranasal FluMist along with the rintatolimod generated specific secretory IgA responses of at least 4 fold over baseline against at least one of the homologous vaccine strains included in the vaccine in 92% of the vaccinees. Additionally, this vaccination strategy induced cross-reactive secretory IgA against highly pathogenic avian influenza virus strains H5N1, H7N9, and H7N3 with pandemic potential for humans. The combination of rintatolimod and FluMist was well-tolerated. PMID- 25128803 TI - Pneumococcal vaccination in people living with HIV. AB - Streptococcus pneumoniae is the leading bacterial opportunistic infection (OI) in HIV positive individuals. Anti-retroviral treatment (ART) reduces their risk of Invasive Pneumococcal Disease (IPD), however, it remains 20- to 40-fold greater than that of the general population. In HIV-infected adults, pneumococcal vaccination (PCV) induces more durable and functional antibody responses in individuals on ART at the time of vaccination than in ART-naive adults, independently of the baseline CD4+ cell count. National guidelines in the UK recommend vaccination in HIV-infected adults with CD4 count >200cells/mL and advise that it be considered for those with CD4 count <200cells/mL(3). We report data on IPD from a London HIV cohort of 3500 north-east London patients from 2009 to 2012. IPD was defined as a positive pneumococcal culture from blood, CSF, joint aspirate or pericardial fluid. HIV positive cases were identified by cross referencing hospital identifiers with a positive HIV Ab/Ag test result or HIV viral load test result on the virology database. There were a total 189 cases of Invasive Pneumococcal Disease identified over the three years. 4.8% (n=9) were known to be HIV positive at the time of their Invasive Pneumococcal infection. The serotypes of S. pneumoniae in the HIV positive cases included 3, 7F, 10F, 19A (n=2), 19F and 31. The estimated incidence of IPD in our HIV cohort was 85.7 per 100,000, (based on an overall HIV cohort size of 3500) which is significantly higher when compared to the general population in London (local epidemiological data reported the incidence rate for IPD at 7.5 per 100,000 in London). Given the higher burden of Invasive Pneumococcal Disease in this cohort, low levels of vaccination, and the predominance of vaccine sensitive strains in our cases, vaccination and strategies to improve vaccine uptake is a priority in this at risk group. PMID- 25128804 TI - Characteristics of test anxiety among medical students and congruence of strategies to address it. AB - INTRODUCTION: Medical students may experience test anxiety associated with 'high stakes' exams, such as Step 1 of the United States Medical Licensing Examination. METHODS: We collected qualitative responses about test anxiety at three points in time from 93 second-year medical students engaged in studying for and taking Step 1. RESULTS: Causes of test anxiety as reported by students were related to negative self-talk during preparation for the exam. Effects of anxiety had to do with emotional well-being, cognitive functioning, and physical well-being. Strategies included socializing with others and a variety of cognitive and physical approaches. Comparison of individuals' strategies with causes and effects showed some congruence, but substantial incongruence between the types of strategies chosen and the reported causes and effects of test anxiety. DISCUSSION: Students' adoption of a 'menu' of strategies rather than one or two carefully selected strategies suggest inefficiencies that might be addressed by interventions, such as advisor-directed conversations with students and incorporating student self-assessment and strategies for managing anxiety within courses on test-taking. Such interventions are in need of further study. An annotated list of evidence-based strategies would be helpful to students and educators. Most important, test anxiety should be viewed by medical educators as a 'real' experience, and students would benefit from educator support. PMID- 25128805 TI - CD31(+) cell transplantation promotes recovery from peripheral neuropathy. AB - Recently, we reported that human peripheral blood (PB)-derived CD31(+) cells are highly angiogenic. In this study, we investigated the beneficial effects of CD31(+) cells on peripheral neuropathy in mice. CD31(+) cells were collected from the peripheral blood using magnetic activated cell sorting. CD31(+) cells exhibited higher levels of expression of angiogenic genes on real-time reverse transcriptase polymerase chain reaction. Peripheral neuropathy was induced by crushing the sciatic nerve with a hemostat, and CD31(+) cells were then injected intramuscularly along the sciatic nerve. CD31(+) cell transplantation restored motor nerve conduction velocity and voltage amplitude and improved motor coordination. In addition, CD31(+) cell transplantation significantly improved blood perfusion and increased intraneural vascularity in the sciatic nerve. Whole mount fluorescent imaging and dot blot analysis showed that CD31(+) cells in the nerve possessed high engraftment and anti-apoptotic properties. Additionally, injected CD31(+) cells displayed neurovascular tropism and are highly incorporated with vasculature. Angiogenic cytokines were augmented in CD31(+) injected nerve tissue, suggesting increased neovascularization. Taken together, these results indicate that CD31(+) cells might be a novel therapeutic strategy in the treatment of peripheral neuropathy. PMID- 25128808 TI - Disruptive innovation: value-based health plans. AB - VALUE AND A COMPLEX HEALTHCARE MARKET: "Worth in usefulness or importance to the possessor; utility or merit." American Heritage Dictionary "A principle, standard, or quality considered worthwhile or desirable." American Heritage Stedman's Medical Dictionary "A fair return or equivalent in goods, services, or money for something exchanged." Merriam-Webster's Dictionary of Law. PMID- 25128807 TI - Building public health capacity in Madhya Pradesh through academic partnership. AB - Engaging in partnerships is a strategic means of achieving objectives common to each partner. The Post Graduate Diploma in Public Health Management (PGDPHM) partners in consultation with the government and aims to strengthen the public health managerial capacity. This case study examines the PGDPHM program conducted jointly by the Public Health Foundation of India and the Government of Madhya Pradesh (GoMP) at the State Institute of Health Management and Communication, Gwalior, which is the apex training and research institute of the state government for health professionals. This is an example of collaborative partnership between an academic institution and the Department of Public Health and Family Welfare, GoMP. PGDPHM is a 1-year, fully residential course with a strong component of field-based project work, and aims to bridge the gap in public health managerial capacity of the health system through training of health professionals. The program is uniquely designed in the context of the National Rural Health Mission and uses a multidisciplinary approach with a focus on inter professional education. The curriculum is competency driven and health systems connected and the pedagogy uses a problem-solving approach with multidisciplinary faculty from different programs and practice backgrounds that bring rich field experience to the classroom. This case study presents the successful example of the interface between academia and the health system and of common goals achieved through this partnership for building capacity of health professionals in the state of Madhya Pradesh over the past 3 years. PMID- 25128806 TI - Tropical influenza and weather variability among children in an urban low-income population in Bangladesh. AB - BACKGROUND: Influenza seasonality in the tropics is poorly understood and not as well documented as in temperate regions. In addition, low-income populations are considered highly vulnerable to such acute respiratory disease, owing to limited resources and overcrowding. Nonetheless, little is known about their actual disease burden for lack of data. We therefore investigated associations between tropical influenza incidence and weather variability among children under five in a poor urban area of Dhaka, Bangladesh. DESIGN: Acute respiratory illness data were obtained from a population-based respiratory and febrile illness surveillance dataset of Kamalapur, a low-income urban area in southeast Dhaka. Analyzed data were from January 2005 through December 2008. Nasopharyngeal wash specimens were collected from every fifth eligible surveillance participant during clinic visits to identify influenza virus infection with viral culture and reverse transcriptase-polymerase chain reaction. Time series analysis was conducted to determine associations between the number of influenza cases per week and weather factors. Zero-inflated Poisson and generalized linear Poisson models were used in the analysis for influenza A and B, respectively. RESULTS: Influenza A had associations with minimum temperature, relative humidity (RH), sunlight duration, and rainfall, whereas only RH was associated with influenza B. Although associations of the other weather factors varied between the two subtypes, RH shared a similar positive association when humidity was approximately 50-70%. CONCLUSIONS: Our findings of a positive RH association is consistent with prior studies, and may suggest the viral response in the tropics. The characteristics of settlement areas, population demographics, and typical overcrowding of urban poverty may also contribute to different impacts of rainfall from higher economic population. Further investigations of associations between tropical influenza and weather variability for urban low-income populations are required for better understanding. PMID- 25128809 TI - PAR polarity: from complexity to design principles. AB - The par-titioning-defective or PAR proteins comprise the core of an essential cell polarity network that underlies polarization in a wide variety of cell types and developmental contexts. The output of this network in nearly every case is the establishment of opposing and complementary membrane domains that define a cell's polarity axis. Yet, behind this simple pattern is a complex system of interactions, regulation and dynamic behaviors. How these various parts combine to generate polarized patterns of protein localization in cells is only beginning to become clear. This review, part of the Special Issue on Cell Polarity, aims to highlight several emerging themes and design principles that underlie the process of cell polarization by components of the PAR network. PMID- 25128810 TI - The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-3beta and ERK1/2 signaling pathway. AB - Hispidin, a phenolic compound from Phellinus linteus (a medicinal mushroom), has been shown to possess strong anti-oxidant, anti-cancer, anti-diabetic, and anti dementia properties. However, the cardioprotective efficacy of hispidin has not yet been investigated. In the present study, we investigated the protective effect of hispidin against oxidative stress-induced apoptosis in H9c2 cardiomyoblast cells and neonatal rat ventricular myocytes. While the treatment of H9c2 cardiomyoblast cells with hydrogen peroxide caused a loss of cell viability and an increase in the number of apoptotic cells, hispidin significantly protected the cells against hydrogen peroxide-induced cell death without any cytotoxicity as determined by XTT assay, LDH release assay, Hoechst 33342 assay, and Western blotting of apoptosis proteins such as caspase-3, Bax, and Bcl-2. Our data also shows that hispidin significantly scavenged intracellular ROS, and markedly enhanced the expression of antioxidant enzymes such as heme oxygenase-1 and catalase, which was accompanied by the concomitant activation of Akt/GSK-3beta and ERK1/2 phosphorylation in H9c2 cardiomyoblast cells. The effects of hispidin on Akt and ERK phosphorylation were abrogated by LY294002 (a PI3K/Akt inhibitor) and U0126 (an ERK1/2 inhibitor). The effect of hispidin on GSK-3b activities was also blocked by LY294002. Furthermore, inhibiting the Akt/GSK-3beta and ERK1/2 pathway by these inhibitors significantly reversed the hispidin-induced Bax and Bcl-2 expression, apoptosis induction, and ROS production. These findings indicate that hispidin protects against apoptosis in H9c2 cardiomyoblast cells exposed to hydrogen peroxide through reducing intracellular ROS production, regulating apoptosis-related proteins, and the activation of the Akt/GSK-3beta and ERK1/2 signaling pathways. PMID- 25128811 TI - Histopathological and in vivo evidence of regucalcin as a protective molecule in mammary gland carcinogenesis. AB - Regucalcin (RGN) is a calcium-binding protein, which has been shown to be underexpressed in cancer cases. This study aimed to determine the association of RGN expression with clinicopathological parameters of human breast cancer. In addition, the role of RGN in malignancy of mammary gland using transgenic rats overexpressing the protein (Tg-RGN) was investigated. Wild-type (Wt) and Tg-RGN rats were treated with 7,12-dimethylbenz[alpha]anthracene (DMBA). Carcinogen induced tumors were histologically classified and the Ki67 proliferation index was estimated. Immunohistochemistry analysis showed that RGN immunoreactivity was negatively correlated with the histological grade of breast infiltrating ductal carcinoma suggesting that progression of breast cancer is associated with loss of RGN. Tg-RGN rats displayed lower incidence of carcinogen-induced mammary gland tumors, as well as lower incidence of invasive forms. Moreover, higher proliferation was observed in non-invasive tumors of Wt animals comparatively with Tg-RGN. Overexpression of RGN was associated with diminished expression of cell-cycle inhibitors and increased expression of apoptosis inducers. Augmented activity of apoptosis effector caspase-3 was found in the mammary gland of Tg RGN. RGN overexpression protected from carcinogen-induced mammary gland tumor development and was linked with reduced proliferation and increased apoptosis. These findings indicated the protective role of RGN in the carcinogenesis of mammary gland. PMID- 25128812 TI - Src inhibition potentiates antitumoral effect of paclitaxel by blocking tumor induced angiogenesis. AB - The protein kinase Src is frequently over-activated in advanced cancers where it modulates the signaling transduction cascade of several growth factors. The feasibility of combination treatment of Src inhibitors with chemotherapy is currently under investigation. We evaluated the anti-tumoral effect of paclitaxel (PTX) in combination with S13, a tyrosine kinase inhibitor with a prevalent specificity for Src, in a hormone-insensible prostate cancer (PCa) cell model. In vivo, combination treatment with PTX and S13 reduced dramatically PCa tumor growth with a relevant difference in the density of new blood vessels with respect to control and single treatments. This reduction was determined by a concomitant impairment of endothelial cell migration and of VEGF release by cancer cells. In fact, S13, when used alone, was sufficient to reduce tubule formation in vivo, and to inhibit VEGFR2 activation and FAK expression in endothelial cells. In addition, the combination treatment determined a significant reduction in ROS production and HIF-1 stabilization in PCa cells respect to single treatments with S13 or PTX. In conclusion, Src-inhibition could be an effective therapeutic strategy aimed at supporting the anti-angiogenic action of PTX in aggressive PCa. PMID- 25128813 TI - Mammalian aPKC/Par polarity complex mediated regulation of epithelial division orientation and cell fate. AB - Oriented cell division is a key regulator of tissue architecture and crucial for morphogenesis and homeostasis. Balanced regulation of proliferation and differentiation is an essential property of tissues not only to drive morphogenesis but also to maintain and restore homeostasis. In many tissues orientation of cell division is coupled to the regulation of differentiation producing daughters with similar (symmetric cell division, SCD) or differential fate (asymmetric cell division, ACD). This allows the organism to generate cell lineage diversity from a small pool of stem and progenitor cells. Division orientation and/or the ratio of ACD/SCD need to be tightly controlled. Loss of orientation or an altered ratio can promote overgrowth, alter tissue architecture and induce aberrant differentiation, and have been linked to morphogenetic diseases, cancer and aging. A key requirement for oriented division is the presence of a polarity axis, which can be established through cell intrinsic and/or extrinsic signals. Polarity proteins translate such internal and external cues to drive polarization. In this review we will focus on the role of the polarity complex aPKC/Par3/Par6 in the regulation of division orientation and cell fate in different mammalian epithelia. We will compare the conserved function of this complex in mitotic spindle orientation and distribution of cell fate determinants and highlight common and differential mechanisms in which this complex is used by tissues to adapt division orientation and cell fate to the specific properties of the epithelium. PMID- 25128815 TI - Hierarchical organization of fetal and adult hematopoietic stem cells. AB - Mammalian hematopoiesis is a hierarchically organized process in which all types of mature blood cells are continuously generated from more primitive cells that lack any morphological evidence of differentiation. However, it is now accepted that this morphologically homogeneous precursor population consists of multiple distinct subsets of cells. The most primitive of these are defined by their ability to produce similarly undifferentiated progeny through many cell divisions, in addition to generating cells with activated differentiation programs. The term hematopoietic stem cell (HSC) is now conventionally restricted to cells with this long-term self-sustaining ability. Nevertheless, clonal tracking studies have revealed significant heterogeneity in the behavior of such stringently defined HSCs. Moreover, superimposed on the heterogeneous behavior that can be elicited from the HSCs present at any given time during development are additional differences that distinguish HSCs at different times both before and after birth. The latter include changes in the representation of HSCs that display specific differentiation programs, as well as changes in their turnover and self-renewal control. Here, we summarize recent studies characterizing these developmental changes, some of the mechanisms that control them, and their potential relevance to understanding age-associated differences in leukemia as well as normal hematopoiesis. PMID- 25128816 TI - Insight in the multilevel regulation of NER. AB - Nucleotide excision repair (NER) is a key component of the DNA damage response (DDR) and it is essential to safeguard genome integrity against genotoxic insults. The regulation of NER is primarily mediated by protein post translational modifications (PTMs). The NER machinery removes a wide spectrum of DNA helix distorting lesions, including those induced by solar radiation, through two sub-pathways: global genome nucleotide excision repair (GG-NER) and transcription coupled nucleotide excision repair (TC-NER). Severe clinical consequences associated with inherited NER defects, including premature ageing, neurodegeneration and extreme cancer-susceptibility, underscore the biological relevance of NER. In the last two decades most of the core NER machinery has been elaborately described, shifting attention to molecular mechanisms that either facilitate NER in the context of chromatin or promote the timely and accurate interplay between NER factors and various post-translational modifications. In this review, we summarize and discuss the latest findings in NER. In particular, we focus on emerging factors and novel molecular mechanisms by which NER is regulated. PMID- 25128814 TI - Raf/MEK/ERK can regulate cellular levels of LC3B and SQSTM1/p62 at expression levels. AB - While cellular LC3B and SQSTM1 levels serve as key autophagy markers, their regulation by different signaling pathways requires better understanding. Here, we report the mechanisms by which the Raf/MEK/ERK pathway regulates cellular LC3B and SQSTM1 levels. In different cell types, DeltaRaf-1:ER- or B-Raf(V600E) mediated MEK/ERK activation increased LC3B-I, LC3B-II, and SQSTM1/p62 levels, which was accompanied by increased BiP/GRP78 expression. Use of the autophagy inhibitors chloroquine and bafilomycin A1, or RNA interference of ATG7, suggested that these increases in LC3B and SQSTM1 levels were in part attributed to altered autophagic flux. However, intriguingly, these increases were also attributed to their increased expression. Upon Raf/MEK/ERK activation, mRNA levels of LC3B and SQSTM1 were also increased, and subsequent luciferase reporter analyses suggested that SQSTM1 upregulation was mediated at transcription level. Under this condition, transcription of BiP/GRP78 was also increased, which was necessary for Raf/MEK/ERK to regulate LC3B at the protein, but not mRNA, level. This suggests that BiP has a role in regulating autophagy machinery when Raf/MEK/ERK is activated. In conclusion, these results suggest that, under a Raf/MEK/ERK activated condition, the steady-state cellular levels of LC3B and SQSTM1 can also be determined by their altered expression wherein BiP is utilized as an effector of the signaling. PMID- 25128817 TI - The Cdk5 activator P39 specifically links muskelin to myosin II and regulates stress fiber formation and actin organization in lens. AB - Cyclin dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase, requires p39 for its enzymatic activity, and is implicated in cytoskeletal organization and contraction in numerous cell types. The C-terminus of p39 binds muskelin, a multi-domain scaffolding protein known to affect cytoskeletal organization, but the mechanisms by which muskelin affects cytoskeletal organization remain unclear. The present study sought to determine whether p39 might serve as an adaptor protein that links muskelin to stress fibers and to investigate the possible biological relevance of such an interaction. Double immunoprecipitation showed that muskelin, p39, and myosin II are components of a single intracellular complex, and suppressing p39 abrogated the interaction between muskelin and the myosin subunits, demonstrating that p39 is required to link muskelin to myosin II. Muskelin is colocalized with myosin regulatory light chain (MRLC) and on stress fibers. The suppression of muskelin reduced Rho-GTP, MRLC phosphorylation, disrupted stress fiber organization, and promoted cell migration, all of which closely mimic the effect of Cdk5 inhibition. Moreover, suppressing muskelin and inhibiting Cdk5 together have no additional effect, indicating that muskelin plays an important role in Cdk5-dependent signaling. p39 is necessary and sufficient for Cdk5-dependent regulation of MRLC phosphorylation, as suppression of p39, but not p35, reduces MRLC phosphorylation. Together, these results demonstrate that p39 specifically links muskelin to myosin II and consequently, to stress fibers and reveal a novel role for muskelin in regulating myosin phosphorylation and cytoskeletal organization. PMID- 25128818 TI - Dose-dependent clearance kinetics of intratracheally administered titanium dioxide nanoparticles in rat lung. AB - AEROSIL((r)) P25 titanium dioxide (TiO2) nanoparticles dispersed in 0.2% disodium phosphate solution were intratracheally administered to male F344 rats at doses of 0 (control), 0.375, 0.75, 1.5, 3.0, and 6.0 mg/kg. The rats were sacrificed under anesthesia at 1 day, 3 days, 7 days, 4 weeks, 13 weeks, and 26 weeks after administration. Ti levels in various pulmonary and extrapulmonary organs were determined using sensitive inductively coupled plasma sector field mass spectrometry. One day after administration, the lungs contained 62-83% of TiO2 administered dose. Twenty-six weeks after administration, the lungs retained 6.6 8.9% of the TiO2 administered at the 0.375, 0.75, and 1.5 mg/kg doses, and 13% and 31% of the TiO2 administered at the 3.0 and 6.0 mg/kg doses, respectively. The pulmonary clearance rate constants from compartment 1, k1, were estimated using a 2-compartment model and were found to be higher for the 0.375 and 0.75 mg/kg doses of TiO2 (0.030/day for both) than for TiO2 doses of 1.5-6.0 mg/kg (0.014-0.022/day). The translocation rate constants from compartment 1 to 2, k12, were estimated to be 0.015 and 0.018/day for the 0.375 and 0.75 mg/kg doses, and 0.0025-0.0092/day for doses of 1.5-6.0mg/kg. The pulmonary clearance rate constants from compartment 2, k2, were estimated to be 0.0086 and 0.0093/day for doses of 0.375 and 0.75 mg/kg, and 0-0.00082/day for 1.5-6.0 mg/kg doses. Translocation of TiO2 from the lungs to the thoracic lymph nodes increased in a time- and dose-dependent manner, accounting for 0.10-3.4% of the administered dose at 26 weeks. The measured thoracic lymph node burdens were a much better fit to the thoracic lymph node burdens estimated assuming translocation from compartment 1 to the thoracic lymph nodes, rather than those estimated assuming translocation from compartment 2 to the thoracic lymph nodes. The translocation rate constants from the lungs to the thoracic lymph nodes, kLung->Lym, were 0.000037-0.00081/day, and these also increased with increasing doses of TiO2. Although a small amount of TiO2 had translocated to the liver by 3 days after the administration (0.0023-0.012% of the highest dose administered, 6.0 mg/kg), translocation to the other extrapulmonary organs was not detected. PMID- 25128819 TI - Tactual perception of liquid material properties. AB - In this paper, studies into the tactual perception of two liquid material properties, viscosity and wetness, are reviewed. These properties are very relevant in the context of interaction with liquids, both real, such as cosmetics or food products, and simulated, as in virtual reality or teleoperation. Both properties have been the subject of psychophysical characterisation in terms of magnitude estimation experiments and discrimination experiments, which are discussed. For viscosity, both oral and manual perception is discussed, as well as the perception of the viscosity of a mechanical system. For wetness, the relevant cues are identified and factors affecting perception are discussed. Finally, some conclusions are drawn pertaining to both properties. PMID- 25128820 TI - Safety pharmacology in 2014: new focus on non-cardiac methods and models. AB - "What do you know about Safety Pharmacology?" This is the question that was asked in 2000 with the inception of the Safety Pharmacology Society (SPS). There is now a widespread awareness of the role of safety pharmacology in drug discovery and increasing awareness among the wider community of methods and models used in the assessment of the core battery required set of safety studies. However, safety pharmacology does not stop with core battery studies. New methods are intensively sought in order to achieve a swifter and more reliable assessment of adverse effect liability. The dynamics of the discipline and method expansion are reflected in the content of this issue of the Journal of Pharmacological and Toxicological Methods (JPTM). We are into the second decade of publishing on safety pharmacology methods and models, reflected by the annual themed issue in JPTM, and on willingness of investigators to embrace new technologies and methodologies. This years' themed issue is derived from the annual Safety Pharmacology Society (SPS) meeting, held in Rotterdam, The Netherlands, in 2013. PMID- 25128821 TI - Redesigning acute care for cognitively impaired older adults: Optimizing health care services. AB - PURPOSE OF THE STUDY: Cognitive impairment (CI) is one of several factors known to influence hospitalization, hospital length of stay, and rehospitalization among older adults. Redesigning care delivery systems sensitive to the influence of CI may reduce acute care utilization while improving care quality. To develop a foundation of fundamental needs for health care redesign, we conducted focus groups with inpatient and outpatient providers to identify barriers, facilitators, and suggestions for improvements in care delivery for patients with CI. DESIGN AND METHODS: Focus group sessions were conducted with providers to identify their approach to caring for cognitively impaired hospitalized adults; obstacles and facilitators to providing this care; and suggestions for improving the care process. Using a thematic analysis, two reviewers analyzed these transcripts to develop codes and themes. RESULTS: Seven themes emerged from the focus group transcripts. These were: (1) reflections on serving the cognitively impaired population; (2) descriptions of perceived barriers to care; (3) strategies that improve or facilitate caring for hospitalized older adults; (4) the importance of fostering a hospital friendly to the needs of older adults; (5) the need for educating staff, patients, and caregivers; (6) the central role of good communication; and (7) steps needed to provide more effective care. IMPLICATIONS: Providing effective acute care services to older adults with CI is an important challenge in health care reform. An understanding derived from the perspective of multiple professional disciplines is an important first step. Future research will build on this preliminary study in developing new acute care models for patients with CI. PMID- 25128823 TI - Mutational analysis of critical residues of FAD-independent catabolic acetolactate synthase from Enterococcus faecalis V583. AB - Catabolic acetolactate synthase (cALS) from Enterococcus faecalis is a FAD independent enzyme, which catalyzes the condensation of two molecules of pyruvate to produce acetolactate. Mutational and kinetic analyses of variants suggested the importance of H111, Q112, and Q411 residues for catalysis in cALS. The wild type and variants were expressed as equally soluble proteins and co-migrated to a size of 60 kDa on SDS-PAGE. Importantly, H111 in cALS, which is widely present as phenylalanine in many other ThDP-dependent enzymes, plays a crucial role in substrate binding. Interestingly, the H111 variants, H111R and H111F, demonstrated altered specific activity of H111 variants with 17- and 26-fold increases in Km, respectively, compared to wild-type cALS. Furthermore, Q112 variants, Q112E, Q112N, and Q112V, exhibited significantly lower specific activity with 70-, 15-, and 10-fold higher Ks for ThDP, respectively. In the case of Q411, the variant Q411E showed a 10-fold rise in Km and a 20-fold increase in Ks for ThDP. Further, the molecular docking results indicated that the binding mode of ThDP was slightly affected in the variants of cALS. Based on these results, we suggest that H111 plays a role in substrate binding, and further suggest that Q112 and Q411 might be involved in ThDP binding of cALS. PMID- 25128822 TI - Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein. AB - Aging and obesity exert important effects on disease. Differentiating these effects is difficult, however, because weight gain often accompanies aging. Here, we used a nested design of aged, calorically restricted, and refed rats to measure changes in brain and blood levels of cytokines and gastrointestinal hormones, brain amyloid precursor protein levels, and brain and body weights. By comparing groups and using path analysis, we found divergent influences of chronological aging versus body weight, our main findings being (i) changes in whole brain weight and serum macrophage colony-stimulating factor levels correlated better with body weight than with chronological aging, (ii) a decrease in brain cytokines and brain plasminogen activator inhibitor levels correlated better with chronological aging than with body weight, (iii) serum erythropoietin levels were influenced by both body weight and aging, (iv) serum plasminogen activator inhibitor, serum cytokines, and brain tumor necrosis factor were not influenced by aging or body weight, and (v) brain amyloid precursor protein more closely related to body weight and serum levels of gastrointestinal hormones than to brain weight, chronological aging, or cytokines. These findings show that although aging and body weight interact, their influences are distinct not only among various cytokines and hormones but also between the central nervous system and the peripheral tissue compartments. PMID- 25128824 TI - Synthesis and characterization of water soluble O-carboxymethyl chitosan Schiff bases and Cu(II) complexes. AB - In this study, mono-imine was synthesized (3a and 4a) via a condensation reaction between 2,4-pentadion and aminobenzoic acid (meta or para) in alcohol (1:1). The second-imine (CS-3a and CS-4a) was obtained as a result of the reaction of the free oxo groups of mono-imine (3a and 4a) with the amino groups on the chitosan (CS). Their structures were characterized with FTIR and (13)C CP-MAS. Then, the water soluble forms of CS-3a and CS-4a were obtained through oxidation of the hydroxide groups on the chitosan to carboxymethyl groups using monochloracetic acid ([O-CMCS-3a] . 2H2O and [O-CMCS-4a] . 2H2O). Thus, the solubility problem of chitosan in an aqueous media was overcome and Cu(II) complexes could be synthesized more easily. Characterization of the synthesized O-carboxymethyl chitosan Schiff base derivatives and their metal complexes, [O-CMCS-3a-Cu(OAc)2] . 2H2O and [O-CMCS-4a-Cu(OAc)2] . 2H2O, was conducted using FTIR, UV-Vis, TG/DTA, XRD, SEM, elemental analysis, conductivities and magnetic susceptibility measurements. PMID- 25128825 TI - Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A. AB - Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro inflammation cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL 10) and transforming growth factor-beta (TGF-beta) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor alpha/beta (ERalpha/beta)-dependent mechanism with the evidence of ERalpha/beta antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor kappaB (NF-kappaB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health. PMID- 25128826 TI - Identification of a telomeric DNA-binding protein in Eimeria tenella. AB - Coccidiosis is considered to be a major problem for the poultry industry, and coccidiosis control is yet urgent. Due to the roles in telomere length regulation and end protection, telomere-binding proteins have been considered as a good target for drug design. In this work, a putative Gbp1p that is similar to telomeric DNA-binding protein Gbp (G-strand binding protein) of Cryptosporidium parvum, was searched in the database of Eimeria tenella. Sequence analysis indicated E.tenella Gbp1p (EtGbp1p) has significant sequence similarity to other eukaryotic Gbps in their RNA recognition motif (RRM) domains. Electrophoretic mobility shift assays (EMSAs) demonstrated recombinant EtGbp1p bound G-rich telomeric DNA, but not C-rich or double-stranded telomeric DNA sequences. Competition and antibody supershift assays confirmed the interaction of DNA protein complex. Chromatin immunoprecipitation assays confirmed that EtGbp1p interacted with telomeric DNA in vivo. Collectively, these evidences suggest that EtGbp1p represents a G-rich single-stranded telomeric DNA-binding protein in E.tenella. PMID- 25128827 TI - PGE2-induced colon cancer growth is mediated by mTORC1. AB - The inflammatory prostaglandin E2 (PGE2) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE2-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE2 EP4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE2-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth. PMID- 25128829 TI - Structure based modification of Bluetongue virus helicase protein VP6 to produce a viable VP6-truncated BTV. AB - Bluetongue virus core protein VP6 is an ATP hydrolysis dependent RNA helicase. However, despite much study, the precise role of VP6 within the viral capsid and its structure remain unclear. To investigate the requirement of VP6 in BTV replication, we initiated a structural and biological study. Multinuclear nuclear magnetic resonance spectra were assigned on his-tagged full-length VP6 (329 amino acid residues) as well as several truncated VP6 variants. The analysis revealed a large structured domain with two large loop regions that exhibit significant conformational exchange. One of the loops (amino acid position 34-130) could be removed without affecting the overall fold of the protein. Moreover, using a BTV reverse genetics system, it was possible to demonstrate that the VP6-truncated BTV was viable in BHK cells in the absence of any helper VP6 protein, suggesting that a large portion of this loop region is not absolutely required for BTV replication. PMID- 25128830 TI - Identification of borrelidin binding site on threonyl-tRNA synthetase. AB - Borrelidin exhibits a wide spectrum of biological activities and has been considered as a non-competitive inhibitor of threonyl-tRNA synthetase (ThrRS). However, the detailed mechanisms of borrelidin against ThrRS, especially borrelidin binding site on ThrRS, are still unclear, which limits the development of novel borrelidin derivatives and rational design of structure-based ThrRS inhibitors. In this study, the binding site of borrelidin on Escherichia coli ThrRS was predicted by molecular docking. To validate our speculations, the ThrRS mutants of E. coli (P424K, E458Delta, and G459Delta) were constructed and their sensitivity to borrelidin was compared to that of the wild-type ThrRS by enzyme kinetics and stopped-flow fluorescence analysis. The docking results showed that borrelidin binds the pocket outside but adjacent to the active site of ThrRS, consisting of residue Y313, R363, R375, P424, E458, G459, and K465. Site-directed mutagenesis results showed that sensitivities of P424K, E458Delta, and G459Delta ThrRSs to borrelidin were reduced markedly. All the results showed that residue Y313, P424, E458, and G459 play vital roles in the binding of borrelidin to ThrRS. It indicated that borrelidin may induce the cleft closure, which blocks the release of Thr-AMP and PPi, to inhibit activity of ThrRS rather than inhibit the binding of ATP and threonine. This study provides new insight into inhibitory mechanisms of borrelidin against ThrRS. PMID- 25128831 TI - Experimental in vitro infection of rat osteoblasts with measles virus stimulates osteogenic differentiation. AB - In this work we characterized the infection of a primary culture of rat osteoblastic lineage cells (OBCs) with measles virus (MeV) and the effect of infection on cell differentiation and maturation. Infection of OBCs with MeV led to high titers of infectivity released early after infection. Also, analysis of mRNAs corresponding to osteogenic differentiation markers like alkaline phosphatase (ALP), bone sialo-protein (BSP) and bone morphogenetic proteins (BMPs) 1-4-5-7 in OBCs revealed higher values (2-75-fold of increment) for infected cells in comparison with uninfected controls. Differentiation of OBCs in osteogenic medium prior to infection influenced the level of stimulation induced by MeV. Furthermore, treatment of OBCs with Ly294002, a PI3K/AKT inhibitor, increased viral titers, whereas treatment with 10MUM or 100MUM ATPgammaS diminished MeV multiplication. In addition, increments of osteogenic differentiation markers induced by MeV infection were not modified either by treatment with Ly294002 or ATPgammaS. These data provide the first evidence demonstrating that MeV can infect osteoblasts in vitro leading to osteoblastic differentiation, a key feature in bone pathogenic processes like otosclerosis. PMID- 25128832 TI - Attitudes and beliefs of health risks associated with sodium intake in diabetes. AB - BACKGROUND: Despite good evidence that reducing sodium intake can reduce blood pressure (BP), salt intake in people with type 1 diabetes (T1DM) or type 2 diabetes (T2DM) remains high. The purpose of this study was to describe the knowledge and beliefs of health risks associated with a high salt diet in adults with diabetes. METHODS: Men and women with T1DM (n = 27; age 38 +/- 16 years) or T2DM (n = 124; age 60 +/- 11 years) were recruited. RESULTS: Nine (6.0%) respondents knew the correct maximum daily recommended upper limit for salt intake. Thirty-six (23.9%) participants were not concerned with the amount of salt in their diet. Most participants knew that a diet high in salt was related to high BP (88.1%) and stroke (78.1%) and that foods such as pizza (80.8%) and bacon (84.8%) were high in salt. Fewer than 30% of people knew that foods such as white bread, cheese and breakfast cereals are high in salt (white bread 28.5%, cheese 29.1%, breakfast cereals 19.9%) and 51.0% correctly ranked three different nutrition information panels based on the sodium content. Label reading and purchase of low salt products was used by 60-80% of the group. Estimated average 24 hour urinary sodium excretion was 169 +/- 32 mmol/24 h in men and 115 +/- 27 mmol/24 h in women. CONCLUSION: Label reading and purchase of low salt products was used by the majority of the group but their salt excretion was still high. Men who used label reading had a lower salt intake. Other strategies to promote a lower sodium intake such as reducing sodium in staple foods such as bread need investigation. PMID- 25128833 TI - "She got more than me". Social comparison and the social context of eating. AB - Eating is a social activity for most people. Other people influence what and how much an individual chooses and eats. Such social influence on eating has long been recognized and studied, but we contend here that one important social influence factor, social comparison, has been largely overlooked by researchers. We review the literature on comparing oneself to others on eating and weight related dimensions, which appears to have an effect not only on eating per se, but also on self-image, body dissatisfaction, and emotions. Social comparison processes may well underlie many of the social influence findings discussed in this special issue. PMID- 25128828 TI - DNA methylation and microRNA biomarkers for noninvasive detection of gastric and colorectal cancer. AB - Cancer initiation and progression is controlled by both genetic and epigenetic events. Epigenetics refers to the study of mechanisms that alter gene expression without permanently altering the DNA sequence. Epigenetic alterations are reversible and heritable, and include changes in histone modifications, DNA methylation, and non-coding RNA-mediated gene silencing. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Aberrant epigenetic modifications occur at the earliest stages of neoplastic transformation and are now believed to be essential players in cancer initiation and progression. Recent advances in epigenetics have not only offered a deeper understanding of the underlying mechanism(s) of carcinogenesis, but have also allowed identification of clinically relevant putative biomarkers for the early detection, disease monitoring, prognosis and risk assessment of cancer patients. At this moment, DNA methylation and non-coding RNA including with microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) represent the largest body of available literature on epigenetic biomarkers with the highest potential for cancer diagnosis. Following identification of cell-free nucleic acids in systematic circulation, increasing evidence has demonstrated the potential of cell-free epigenetic biomarkers in the blood or other body fluids for cancer detection. In this article, we summarize the current state of knowledge on epigenetic biomarkers - primarily DNA methylation and non-coding RNAs - as potential substrates for cancer detection in gastric and colorectal cancer, the two most frequent cancers within the gastrointestinal tract. We also discuss the obstacles that have limited the routine use of epigenetic biomarkers in the clinical settings and provide our perspective on approaches that might help overcome these hurdles, so that these biomarkers can be readily developed for clinical management of cancer patients. PMID- 25128834 TI - Food references and marketing in popular magazines for children and adolescents in New Zealand: a content analysis. AB - Food marketing is recognized as an important factor influencing children's food preferences and consumption. The purpose of this study was to examine the nature and extent of unhealthy food marketing and non-branded food references in magazines targeted at and popular among children and adolescents 10-17 years old in New Zealand. A content analysis was conducted of all food references (branded and non-branded) found in the five magazines with the highest readership among 10 17 year olds, and the three magazines (of which two were already included among the five most popular magazines) targeted to 10-17 year olds. For each of the six magazines, one issue per month (n = 72 issues in total) over a one-year period (December 2012-January 2014) was included. All foods referenced were classified into healthy/unhealthy according to the food-based Ministry of Health classification system. Branded food references (30% of total) were more frequent for unhealthy (43%) compared to healthy (25%) foods. Magazines specifically targeted to children and adolescents contained a significantly higher proportion of unhealthy branded food references (n = 51/71, 72%) compared to the most popular magazines among children and adolescents (n = 133/317, 42%), of which most were targeted to women. 'Snack items' such as chocolates and ice creams were marketed most frequently (n = 104; 36%), while 'vegetables and fruits' were marketed the least frequently (n = 9; 3%). Direct advertisements accounted for 27% of branded food references and 25% of those featured health or nutrition claims. Both branded and non-branded food references were common within magazines targeted at and popular among children and adolescents, and skewed toward unhealthy foods. This raises concerns about the effectiveness of self-regulation in marketing and emphasizes that government regulations are needed in order to curb children's current potential high exposures to unhealthy food marketing. In addition, magazine editors could take socially responsible editorial positions in regard to healthy eating. PMID- 25128835 TI - The effect of non-caloric sweeteners on cognition, choice, and post-consumption satisfaction. AB - Consumers often turn to non-caloric sweeteners (NCS) as a means of promoting a healthy body weight. However, several studies have now linked their long-term use to increased weight gain, raising the question of whether these products produce unintended psychological, physiological, or behavioral changes that have implications for weight management goals. In the following, we present the results of three experiments bearing on this issue, testing whether NCS consumption influences how individuals think about and respond to food. Participants in each of our three experiments were randomly assigned to consume a sugar-sweetened beverage, an unsweetened beverage, or a beverage sweetened with NCS. We then measured their cognition (Experiment 1), product choice (Experiment 2), and subjective responses to a sugar-sweetened food (Experiment 3). Results revealed that consuming NCS-sweetened beverages influences psychological processes in ways that - over time - may increase calorie intake. PMID- 25128836 TI - Transcranial direct current stimulation modulates ERP-indexed inhibitory control and reduces food consumption. AB - Food craving can be defined as the "urge to eat a specific food". Previous findings suggest impairment of inhibitory control, specifically a regulatory deficit in the lateral prefrontal circuitry that is associated with a compulsion for food. As demonstrated by three previous studies, bilateral transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) (anode right/cathode left) reduces food craving and caloric intake. We designed the present study to evaluate the neural mechanisms that underlie these effects. We replicated the design of one of these previous studies but included electroencephalographic assessments to register evoked potentials in a Go/No-go task that contained pictures of food and furniture (a control visual stimulus). We collected data from nine women (mean age = 23.4 +/- 2 years) in a crossover experiment. We observed that active DLPFC tDCS (anode right/cathode left), compared with sham stimulation, reduced the frontal N2 component and enhanced the P3a component of responses to No-go stimuli, regardless of the stimulus condition (food or furniture). Active tDCS was also associated with a reduction in caloric intake. We discuss our findings in the context of cortico-subcortical processing of craving and tDCS effects on inhibitory control neural circuitry. PMID- 25128837 TI - Shoppers' perceived embeddedness and its impact on purchasing behavior at an organic farmers' market. AB - This study explores the concept of perceived embeddedness (PE) and its impact on purchasing behavior at an organic farmers' market. Based on a review of the prior literature, the study refines the conceptualization and measurement of PE as a second-order factor construct reflected in its three dimensions: perceived social embeddedness, perceived spatial embeddedness, and perceived natural embeddedness. The study also suggests that organic farmers' market shoppers' PE is positively related to the two measures of purchasing behavior: expenditure per visit and repurchase intention. In a sample of 492 organic farmers' market shoppers in Beijing municipality, China, the study find support for the second-order factor structure of PE and the theorized relationship between the shoppers' PE and their purchasing behavior. The study also discusses theoretical and managerial implications of the findings. PMID- 25128838 TI - Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: case-control cross-sectional study. AB - OBJECTIVE: Vascular endothelial growth factor A (VEGF) and its receptor KDR play central roles in angiogenesis and vascular repair, which occur in diabetic vascular complications, such as MI. The aim of our study was to investigate if polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM). DESIGN AND METHODS: The association of KDR -604T>C (rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case-control cross-sectional study including 171 subjects with T2DM and MI compared to 855 subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum levels were analyzed in 98 subjects with type 2 diabetes without CAD. RESULTS: A significantly higher frequency of the CC genotype of the KDR -604T>C (rs2071559) polymorphism was found in diabetic patients with MI compared to diabetic patients without CAD (27.5% vs. 21.1%, p=0.04). On the other hand, the 1192G>A (rs2305948) polymorphism was not associated with MI in subjects with type 2 diabetes. Significantly higher VEGF serum levels were found in subjects with the -604CC genotype compared to those with other (CT+TT) genotypes (73.8 +/- 22.1 ng/l vs. 58.1 +/- 18.5 ng/l; p<0.01). Multiple logistic regression analysis adjusted for age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed that carriers of the -604CC genotype (rs2071559) had a 1.6-fold higher risk for MI (OR=1.6; 95% CI=1.1-2.1; p=0.022). CONCLUSION: The present study demonstrates that the CC genotype of the KDR -604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM. PMID- 25128839 TI - Development and validation of a UHPLC diode array detector method for meropenem quantification in human plasma. AB - OBJECTIVES: Meropenem is a beta-lactam antibiotic frequently used to treat serious infections in intensive care unit patients. The main objective was to develop and validate a sensitive and specific ultra high performance liquid chromatography method with photodiode array detection for the quantitation of meropenem in human plasma. The applicability of the method for meropenem monitoring was also examined. DESIGN AND METHODS: The validation of the method was performed following the FDA's guidelines for bioanalytical methods. In parallel, the method was applied for monitoring meropenem in forty plasma samples from ten critically ill patients treated intravenously at a total dose of 1 g. Drug levels were measured in each patient at 0 h, 2 h, 4 h and 8 h after meropenem infusion. RESULTS: With this method, intraday and day-to-day variation was below 10%; intraday and day-to-day accuracy was between 94% and 114%; the limit of quantification was 0.5 MUg/mL and recovery was above 70%. The method was successfully applied to quantitate meropenem concentrations and the results showed significant pharmacokinetic interindividual variability. Of special interest is that 50% of treated patients had meropenem plasma levels below the minimum inhibitory concentration at 8h after the start of infusion, which was strongly related to creatinine clearance >60 mL/min. CONCLUSIONS: The method meets the requirements to be applied for meropenem concentration measurements in pharmacokinetics studies and clinical routine. The results suggest the need for therapeutic drug monitoring of meropenem in treated critically-ill patients. PMID- 25128840 TI - Variable effects of the co-administration of a GM-CSF-expressing plasmid on the immune response to flavivirus DNA vaccines in mice. AB - As a cytokine adjuvant, granulocyte-macrophage colony-stimulating factor (GM-CSF) has been demonstrated to play central roles in the enhancement of the immune response and protection elicited by experimental vaccines. However, in our previous work, the co-administration of GM-CSF produced untoward effects on the immune response induced by a Japanese encephalitis virus DNA vaccine candidate. This study aimed to elucidate the adjuvant roles of GM-CSF in several Flaviviridae virus DNA vaccine candidates. Our results showed that the effects of GM-CSF were diverse: co-inoculated GM-CSF caused significant suppression to the dengue virus type 1 and type 2 prM-E DNA vaccinations and influenced protective efficiency against virus challenge. In contrast, GM-CSF showed little effect or an enhancement on the immune response elicited by hepatitis C virus C or E1 DNA vaccine candidates. Notably, these effects of GM-CSF were highly durable. Our results suggested that the adjuvant roles of the GM-CSF plasmid were complex and diverse, ranging from enhancement to suppression, depending on the immunogen of Flaviviridae virus DNA vaccine candidates. Therefore, the application of GM-CSF as a vaccine adjuvant or a therapeutic agent should be evaluated carefully. PMID- 25128841 TI - Murine carcinoma expressing carcinoembryonic antigen-like protein is restricted by antibody against neem leaf glycoprotein. AB - We have generated a polyclonal antibody against a novel immunomodulator, neem leaf glycoprotein (NLGP) that can react to a specific 47 kDa subunit of NLGP. Generated anti-NLGP antibody (primarily IgG2a) was tested for its anti-tumor activity in murine carcinoma (EC, CT-26), sarcoma (S180) and melanoma (B16Mel) tumor models. Surprisingly, tumor growth restriction was only observed in CT-26 carcinoma models, without any alteration in other tumor systems. Comparative examination of antigenicity between four different tumor models revealed high expression of CEA-like protein on the surface of CT-26 tumors. Subsequent examination of the cross-reactivity of anti-NLGP antibody with purified or cell bound CEA revealed prominent recognition of CEA by anti-NLGP antibody, as detected by ELISA, Western Blotting and immunohistochemistry. This recognition seems to be responsible for anti-tumor function of anti-NLGP antibody only on CEA like protein expressing CT-26 tumor models, as confirmed by ADCC reaction in CEA(+) tumor systems where dependency to anti-NLGP antibody is equivalent to anti CEA antibody. Obtained result with enormous therapeutic potential for CEA(+) tumors may be explained in view of the epitope spreading concept, however, further investigation is crucial. PMID- 25128842 TI - And the BBI 2014 award for lead actor in "neuroinflammation and depression" goes to.... PMID- 25128843 TI - Fractal microstructure characterization of wet microalgal cells disrupted with ultrasonic cavitation for lipid extraction. AB - The effects of ultrasonic treatment on fractal microstructures of wet microalgal cells were investigated for lipid extraction. Fractal dimension of cells with distorted surfaces increased with power and ultrasonication time. Microalgal cells shrank owing to dehydration and cytomembranes were reduced to debris, but cell walls were not fragmented. When ultrasonication power increased from 0 to 500W for 30min, the fractal dimension of cells increased from 1.21 to 1.51, cell sizes decreased from 2.78 to 1.68MUm and cell wall thickness decreased from 0.08 to 0.05MUm. When ultrasonication time increased from 5 to 30min with a power of 150W, the fractal dimension of cells increased from 1.24 to 1.37, cell sizes decreased from 2.72 to 2.38MUm and cell wall thickness first increased to a peak of 0.22MUm and then decreased. Long-chain and unsaturated lipids were degraded into short-chain and saturated lipids with ultrasonic cavitation. PMID- 25128844 TI - Recycling of food waste as nutrients in Chlorella vulgaris cultivation. AB - Heterotrophic cultivation of Chlorella vulgaris was investigated in food waste hydrolysate. The highest exponential growth rate in terms of biomass of 0.8day( 1) was obtained in a hydrolysate consisting of 17.9gL(-1) glucose, 0.1gL(-1) free amino nitrogen, 0.3gL(-1) phosphate and 4.8mgL(-1) nitrate, while the growth rate was reduced in higher concentrated hydrolysates. C. vulgaris utilized the nutrients recovered from food waste for the formation of biomass and 0.9g biomass was produced per gram glucose consumed. The microalgal biomass produced in nutrient sufficient batch cultures consisted of around 400mgg(-1) carbohydrates, 200mgg(-1) proteins and 200mgg(-1) lipids. The conversion of nutrients derived from food waste and the balanced biomass composition make C. vulgaris a promising strain for the recycling of food waste in food, feed and fuel productions. PMID- 25128845 TI - OmGOGAT-disruption in the ericoid mycorrhizal fungus Oidiodendron maius induces reorganization of the N pathway and reduces tolerance to heavy-metals. AB - Mycorrhizal fungi are key mediators of soil-to-plant movement of mineral nutrients, including essential and non-essential metals. In soil conditions that facilitate mobilization of metal ions, potentially toxic metals can interfere with nitrogen metabolism in both plants and microorganisms. Less is known about possible relationships between nitrogen metabolism and responses to heavy metals. Aim of this study was to investigate this aspect in the ericoid mycorrhizal fungus Oidiodendron maius strain Zn, a metal tolerant ascomycete. Growth of O. maius Zn on zinc and cadmium containing media was significantly affected by the nitrogen source. Screening of a library of O. maius Zn random genetic transformants for sensitivity to heavy metals (zinc and cadmium) and oxidative stress (menadione) yielded a mutant strain that carried a partial deletion of the glutamate synthase (NADH-GOGAT EC 1.4.1.14) gene and its adjacent gene, the APC15 subunit of the anaphase promoting complex. Comparison of WT and OmGOGAT-OmAPC15 mutant strains indicated an impaired N-metabolism and altered stress tolerance, and assays on the OmAPC15-recomplemented strains ascribed the observed phenotypes to the deletion in the OmGOGAT gene. OmGOGAT disruption modified the nitrogen pathway, with a strong reduction of the associated glutamine synthetase (GS, EC 6.3.1.2) activity and an up-regulation of the alternative NADP-glutamate dehydrogenase (NADP-GDH, EC 1.4.1.4) pathway for glutamate biosynthesis. Unless they were supplemented with glutamine, O. maius Zn transformants lacking OmGOGAT were very sensitive to zinc. These results highlight the importance of nitrogen metabolism not only for nitrogen assimilation and transformation, but also for stress tolerance. For mycorrhizal fungi, such as O. maius, this may bear consequences not only to the fungus, but also to the host plant. PMID- 25128846 TI - Sperm glucose transport and metabolism in diabetic individuals. AB - Individuals with diabetes mellitus (DM) present marked reduction in sperm quality and higher DNA damage in spermatozoa, evidencing that this metabolic disorder impairs male fertility. These effects are related to defective testicular metabolic pathways and signaling, resulting in altered sperm metabolism. Spermatozoa metabolize several substrates to ensure energy supplies and any alteration in this feature compromise sperm quality. For ATP production, spermatozoa require substrate availability and the involvement of specific hexose membrane carriers. DM is known to modulate the spermatozoa substrate consumption and/or production due to altered glycolytic behavior. In fact, glucose uptake and metabolism is highly deregulated in diabetic individuals. Herein, we present an overview of the implications of DM in sperm glucose uptake and metabolism. The understanding of these processes is essential to identify key mechanisms associated with DM-related male (in)fertility. Moreover, it may contribute to the development of therapeutics to counteract the dysfunction induced by DM in sperm metabolism. PMID- 25128847 TI - Glutamine synthetase plays a role in D-galactose-induced astrocyte aging in vitro and in vivo. AB - Astrocytes play multiple roles in physiological and pathological conditions in brain. However, little is known about the alterations of astrocytes in age related changes, and few aging models of the astrocytes in vitro have been established. Therefore, in the present study, we used d-galactose (D-Gal) to establish astrocyte aging model to explore the alterations of astrocytes in brain aging. We also used (1)H nuclear magnetic resonance ((1)H NMR) spectra to verify the metabolic changes in the cerebral cortex of mice injected with D-gal. The results showed that D-gal (55mM) treatment for 1 week induced senescence characteristics in cultured cortical astrocytes. Real-time PCR and western blot analysis showed that the levels of glutamine synthetase (GS) mRNA and protein were strikingly decreased in the cultured senescent astrocytes, and the senescent astrocytes showed less resistance to the glutamate-induced gliotoxicity. The impairments of glutamate-glutamine cycle and astrocytes were also found in the cerebral cortex of mice treatment with D-gal (100mg/kg) for 6 weeks, and the level of GS mRNA was also found to be reduced markedly, being consistent with the result obtained from the senescent astrocytes in vitro. These results indicate that astrocyte may be the predominant contributor to the pathogenic mechanisms of D-gal-induced brain aging in mice, and GS might be one of the potential therapeutic targets of the aged brain induced by D-gal. PMID- 25128849 TI - Spinal administration of mGluR5 antagonist prevents the onset of bortezomib induced neuropathic pain in rat. AB - Peripheral neuropathy is a common adverse effect of bortezomib-based chemotherapy. In this study we have investigated the role played by subtype 5 of metabotropic receptors in bortezomib induced peripheral neuropathy. Rats were administered with bortezomib three times weekly at 0.20 mg/kg for a total of 4 weeks in presence or absence of mGluR5 antagonist MPEP. The animals were submitted to paw-pressure test and tail sensory nerve conduction measurement more times during the treatment and follow-up. Bortezomib treatment induced a progressively increasing hyperalgesia in rat which was accompanied by a significant reduction in sensory nerve conduction velocity (SNCV). MPEP prevented the emergence of bortezomib-induced pain and counteracted SNCV reduction when co administered with bortezomib treatment. Spinal extracellular glutamate levels increased in rats treated with bortezomib. Bortezomib-induced onset of the hyperalgesia and SNCV decrease could be prevented by agents that promote the reuptake of glutamate maintaining spinal glutamate at basal level. Our data support the manipulation of the glutamatergic system through the mGluR5 receptor in bortezomib induced peripheral neuropathy. The use of antagonists at the mGluR5, initiated at the same time as bortezomib-chemotherapy, might reduce the number of patients who develop painful peripheral chemo-neuropathy. PMID- 25128850 TI - Altered expression of deltaGABAA receptors in health and disease. AB - gamma-Aminobutyric acid type A receptors that contain the delta subunit (deltaGABAA receptors) are expressed in multiple types of neurons throughout the central nervous system, where they generate a tonic conductance that shapes neuronal excitability and synaptic plasticity. These receptors regulate a variety of important behavioral functions, including memory, nociception and anxiety, and may also modulate neurogenesis. Given their functional significance, deltaGABAA receptors are considered to be novel therapeutic targets for the treatment of memory dysfunction, pain, insomnia and mood disorders. These receptors are highly responsive to sedative-hypnotic drugs, general anesthetics and neuroactive steroids. A further remarkable feature of deltaGABAA receptors is that their expression levels are highly dynamic and fluctuate substantially during development and in response to physiological changes including stress and the reproductive cycle. Furthermore, the expression of these receptors varies in pathological conditions such as alcoholism, fragile X syndrome, epilepsy, depression, schizophrenia, mood disorders and traumatic brain injury. Such fluctuations in receptor expression have significant consequences for behavior and may alter responsiveness to therapeutic drugs. This review considers the alterations in the expression of deltaGABAA receptors associated with various states of health and disease and the implications of these changes. PMID- 25128848 TI - Metaplastic effects of subanesthetic ketamine on CA1 hippocampal function. AB - Ketamine is a non-competitive N-methyl-d-aspartate receptor (NMDAR) antagonist of interest in neuropsychiatry. In the present studies, we examined the effects of subanesthetic, low micromolar ketamine on excitatory postsynaptic potentials (EPSPs), population spikes (PSs) and synaptic plasticity in the CA1 region of rat hippocampal slices. Ketamine acutely inhibited NMDAR-mediated synaptic responses with half-maximal effects near 10 MUM. When administered for 15-30 min at 1-10 MUM, ketamine had no effect on baseline dendritic AMPA receptor-mediated EPSPs, but persistently enhanced somatic EPSPs in the pyramidal cell body layer and augmented PS firing. Acute low micromolar ketamine also had no effect on the induction of long-term potentiation (LTP) but blocked long-term depression (LTD). Following 30 min administration of 1-10 MUM ketamine, however, a slowly developing and persistent form of LTP inhibition was observed that took two hours following ketamine washout to become manifest. This LTP inhibition did not result from prolonged or enhanced NMDAR inhibition during drug washout. Effects of low ketamine on somatic EPSPs and LTP were not mimicked by a high ketamine concentration that completely inhibited NMDARs, and both of these effects were blocked by co-administration of low ketamine with a low concentration of the competitive NMDAR antagonist, 2-amino-5-phosphonovalerate or inhibitors of nitric oxide synthase. These results indicate that concentrations of ketamine relevant to psychotropic and psychotomimetic effects have complex metaplastic effects on hippocampal function that involve activation of unblocked NMDARs during ketamine exposure. PMID- 25128851 TI - Hysteroscopic morcellation: review of the manufacturer and user facility device experience (MAUDE) database. AB - STUDY OBJECTIVE: To investigate the number and type of adverse events associated with hysteroscopic morcellation of intrauterine disease. DESIGN: Systematic review of Manufacturer and User Device Experience (MAUDE) database from 2005 to June 2014 (Canadian Task Force classification III). SETTING N/A PATIENTS: Women undergoing hysteroscopic surgery for removal of intrauterine polyps or myomas with use of a reciprocating morcellator. INTERVENTIONS: The MAUDE database was searched for the key words "Hysteroscope," "Hysteroscopic reciprocating morcellator," "Interlace," "MyoSure," "Smith & Nephew," and "TRUCLEAR," to identify reported incidences of device malfunction, injury, or death. A total of 119 adverse events were analyzed. Reports were reviewed individually and categorized by date of occurrence, type of morcellation device, type of complication, and a brief description. Each company was contacted to provide an estimate of the number of procedures performed or units sold to date. MEASUREMENTS AND MAIN RESULTS: From 2005 to June 2014, 119 adverse events were reported to the MAUDE database. On the basis of severity, adverse events were categorized as major or minor complications. Major events included intubation/admission to an intensive care unit (n = 14), bowel damage (n = 12), hysterectomy (n = 6), and death (n = 2). Minor events included uterine perforation requiring no other treatment (n = 29), device failure (n = 25), uncomplicated fluid overload (n = 19), postoperative bleeding controlled using noninvasive measures (n = 6), and pelvic infection (n = 4). These events were then categorized according to manufacturer. The number of adverse events reported to the MAUDE database was divided by the total units sold as a surrogate for the estimated number of procedures performed. Understanding the limitation of the numbers used as a numerator and denominator, we concluded that adverse events complicated hysteroscopic morcellation in <0.1% cases. CONCLUSIONS: The suction based, mechanical energy, rotating tubular cutting system was developed to overcome adverse events that occur during traditional resectoscopy. On the basis of acknowledged limited information from the MAUDE database, it seems that life threatening complications such as fluid overload, uterine perforation, and bleeding do occur with hysteroscopic morcellation but less frequently than with traditional electrocautery. PMID- 25128852 TI - Development of chitosan oleate ionic micelles loaded with silver sulfadiazine to be associated with platelet lysate for application in wound healing. AB - In the treatment of chronic wounds, topical application of anti-infective drugs such as silver sulfadiazine (AgSD) is of primary importance to avoid infections and accelerate wound repair. AgSD is used in burns and chronic wounds for its wide antibacterial spectrum, but presents limitations due to poor solubility and cytotoxicity. In the present work polymeric micelles obtained by self-assembling of chitosan ionically modified by interaction with oleic acid were developed as carriers for AgSD to overcome the drawbacks of the drug. The AgSD loaded micelles were intended to be associated in wound healing with platelet lysate (PL), a hemoderivative rich in growth factors. Unloaded micelles demonstrated good compatibility with both fibroblasts and PL. The relevance of chitosan concentration and of the ratio between chitosan and oleic acid to the drug loading and the particle size of nanoparticles was studied. A marked increase (up to 100 times with respect to saturated solution) of AgSD concentration in micelle dispersion was obtained. Moreover, the encapsulation reduced the cytotoxic effect of the drug towards fibroblasts and the drug incompatibility with PDGF-AB (platelet derived growth factor), chosen as representative of platelet growth factors. PMID- 25128853 TI - Study of the Lactobacillus rhamnosus Lcr35(r) properties after compression and proposition of a model to predict tablet stability. AB - The beneficial effects of probiotic bacteria on human health are now widely acknowledged, and this has prompted growing interest in research and development in the pharmaceutical field. However, to be viable when they reach their target, the bacteria must be able to survive during the manufacturing process and the biological pathway. Tablet form best meets the requirements for protecting acid labile drugs, but the tableting process could be an additional stress for the bacteria. This study evaluated the initial effect of compression pressure on the Lcr35(r) strain in a vaginal (Lcr regenerans(r)) and an intestinal (Lcr restituo(r)) formulation. A stability study was also performed on the tablets and revealed a beneficial effect of this form. The obtained destruction rates (k) demonstrated that the bacterial stability was greater in tablets than in powders (kpowders>ktablets). A new mathematical model was developed combining compression and temperature parameters to predict the bacterial viability at any pressure and time. Moreover, the genetic profile of Lcr35(r) (Rep-PCR, microarrays), its resistance to acidity and its ability to inhibit Candidaalbicans growth, after compression, were determined to evaluate the target product profile (TPP) in a Quality by Design (QbD) approach. The Rep-PCR analysis validated the strain identity and the microarrays demonstrated the genetic stability of Lcr35(r) strain after compaction. Additionally, ability to inhibit the C. albicans growth was maintained and the resistance to gastric conditions of Lcr35(r) was even improved by tableting. As a dosage form, tablets containing probiotic can guarantee that an adequate amount of bacteria reaches the therapeutic target (intestinal or vaginal) and that the product remains stable until the time of consumption. PMID- 25128854 TI - Development of disulfiram-loaded vaginal rings for the localised treatment of cervical cancer. AB - Cervical cancer is the third most prevalent cancer in women and disproportionately affects those in low resource settings due to limited programs for screening and prevention. In the developed world treatment for the disease in the non-metastasised state usually takes the form of surgical intervention and/or radiotherapy. In the developing world such techniques are less widely available. This paper describes the development of an intravaginal ring for the localised delivery of a chemotherapeutic drug to the cervix that has the potential to reduce the need for surgical intervention and will also provide a novel anti cancer therapy for women in low resource settings. Disulfiram has demonstrated antineoplastic action against prostate, breast and lung cancer. Both PEVA and silicone elastomer were investigated for suitability as materials in the manufacture of DSF eluting intravaginal rings. DSF inhibited the curing process of the silicone elastomer, therefore PEVA was chosen as the material to manufacture the DSF-loaded vaginal rings. The vaginal rings had an excellent content uniformity while the DSF remained stable throughout the manufacturing process. Furthermore, the rings provided diffusion controlled release of DSF at levels well in excess of the IC50 value for the HeLa cervical cancer cell line. PMID- 25128855 TI - Expression of biologically active TAT-fused recombinant islet transcription factors. AB - AIMS: Differentiation of pancreatic endocrine cells depends upon the activation of genes that are regulated by islet transcription factors (ITFs). Evidence suggests that ITFs contribute to the development of the pancreas. These studies are focused on developing a system to deliver individual ITF from different stages of islet cell development to promote precursors or other cell types to trans-differentiate into islet-like insulin-positive cells. MAIN METHODS: Protein transduction domains (PTDs) derived from the HIV-TAT peptide (YGRKKRRQRRR) were fused with three ITFs, Ngn3, Pdx1, and NeuroD/beta2, to facilitate the uptake of ITF recombinant proteins into various cell types. The three TAT-fused ITFs, Ngn3, Pdx1, and NeuroD/beta2 were constructed in a bacterial 6*His affinity tag-TAT recombinant protein expression system. The recombinant proteins were expressed using IPTG induction and purified to homogeneity using a nickel affinity column. KEY FINDINGS: The biological activity of each TAT-fused ITF was demonstrated by nuclear translocation, induction of target gene promoter activity, and the trans differentiation of pancreatic acinar cells, AR42J, into insulin-positive cells. SIGNIFICANCE: This study provides advanced information for developing strategies using recombinant TAT-fused ITF proteins in place of adenoviral vectors for the conversion of pancreatic exocrine cells into insulin-positive cells for the treatment of diabetes. PMID- 25128856 TI - Epigenetics, the missing link in hypertension. AB - Epigenetics refers to functional alterations in gene expression or phenotype without any change of the underlying DNA sequence. It is the study of the potential of a cell or organism to express different traits through functional regulation of its gene transcription. Though it is met as a necessary process in biology, epigenetics may often play a crucial part in the development of specific pathologic conditions, including cardiovascular diseases and hypertension. PMID- 25128857 TI - Structure and biological perspectives of Cu(II)-indomethacin complexes. AB - The copper(II) complexes with the non-steroidal anti-inflammatory drug indomethacin (Hindo) in the presence of the nitrogen-donor heterocyclic ligands 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2'-bipyridylamine (bipyam) have been synthesized and characterized. The crystal structures of [Cu(indo)2(bipy)]?1.5MeOH?0.5H2O and [Cu(indo)2(phen)] ?1.85MeOH?0.15H2O have been determined by X-ray crystallography. All compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity with the previously reported complex [Cu2(indo)4(H2O)2] being the most active. The complexes exhibit good binding affinity to human or bovine serum albumin protein with high binding constant values. UV study of the interaction of the complexes with calf-thymus (CT) DNA has shown that the complexes can bind to CT DNA with [Cu(indo)2(bipyam)] showing the highest binding constant to CT DNA (Kb=1.56(+/-0.19)*10(6)M(-1)). The complexes can bind to CT DNA via intercalation as concluded by cyclic voltammetry, DNA viscosity measurements and competitive studies with ethidium bromide (EB) which revealed the ability of the complexes to displace the DNA-bound EB. PMID- 25128858 TI - How well do patient activation scores predict depression outcomes one year later? AB - BACKGROUND: This study examines the relationship between patient activation, a measure of individuals' knowledge, skill, and confidence for managing their health, and rates of depression remission and response among patients with depression. METHODS: Patients from Fairview Health Services in Minnesota with moderate to severe depression in 2011 and a PHQ-9 score in 2012 were included in the analysis (n=5253). Patient activation in 2011 and other health and demographic features were extracted from the electronic health record. We examined how patient activation predicted depression remission and response rates and changes in depression severity over one year using regression models. We also explored how activation predicted healthy behaviors among depressed patients. RESULTS: Higher baseline patient activation predicted lower depression severity and higher depression remission and response rates a year later. The most activated patients had PHQ-9 scores in 2012 two points lower than the lowest activated patients, and they had twice the odds of remission. Activation also predicted increase in healthy behaviors. LIMITATIONS: We were unable to examine the use of mental health services or control for the number of prior depressive episodes and duration of the current depressive episode in the analysis. CONCLUSIONS: We found that higher patient activation predicted better depression outcomes. While we are unable to explore the mechanism of this association, we observed that more activated patients are also engaged in more healthy behaviors, suggesting that the mechanism may be behavioral. Support of patient activation may be an effective approach for providers to reduce patients' depression severity. PMID- 25128859 TI - Cyberbullying, psychological distress and self-esteem among youth in Quebec schools. AB - BACKGROUND: The advent of new technologies and social media offers a host of possibilities for teenagers to consolidate social networks. Unfortunately, new technologies also represent a potential setting for experiences of victimization. METHODS: The present study explores the prevalence of cyberbullying victimization in a representative sample of 8 194 teenagers in Quebec and the adverse associated consequences. RESULTS: Results indicate that 18% of boys and close to 1 out of 4 girls report at least one incident of cyberbullying in the past 12 months. Cyberbullying victimization contributes to the prediction of low selfesteem and psychological distress over and above other experiences of bullying in schools or other settings. CONCLUSIONS: Cyberbullying appear as one important target for the design of prevention and intervention services designed for youth. PMID- 25128860 TI - Factors associated with depression and suicide attempts in patients undergoing rehabilitation for substance abuse. AB - BACKGROUND: Comorbidity of major depression with substance abuse increases the risk of committing suicide. The objective of this work was to determine the psychological and socio-demographic factors associated with depression and suicide attempts in patients rehabilitating for drug consumption. METHOD: 57 Patients attending a center for drug abuse treatment answered the following instruments: the Mini-international neuropsychiatric interview, a questionnaire of general information and background data on consumption of substances, depression and suicide attempts, and the Spanish adaptation of the Holmes and Rahe scale for the assessment of life events. Chi-square and logistic regression tests were used to establish associations between variables. RESULTS: 68.4% of the Patients had current major depression, of these, 75.4% experienced it before the onset of substance abuse. Patients attempting suicide before drug use corresponded to 26%, whilst 28.1% attempted suicide within the last year. Current depression-related variables were receiving a diagnosis of depression prior to the consumption of drugs and the first used drugs, which were alcohol or marijuana. The adverse life event "Familial drug abuse history", was also significantly related to depression (p=0.02). Variables associated with current suicide attempts were: receiving a diagnosis of depression prior to the consumption of drugs (p=0.02), and suicide attempts previous to drug use (p<0.003). LIMITATION: A limitation of this study was the small size of the sample. CONCLUSION: Patients with depression who attempted suicide prior to the use of drugs also experienced these conditions during the rehabilitation process. Substance use in the family was a risk factor for both, underscoring the need of actions aimed at preventing addictions in the household environment. PMID- 25128861 TI - A review of the relationship between proinflammatory cytokines and major depressive disorder. AB - BACKGROUND: Determining etiological factors and reviewing advances in diagnostic modalities sensitive and specific to Major Depressive Disorder (MDD) is of importance in its evaluation and treatment. The inflammatory hypothesis is one of the most prevalent topics concerning MDD and may provide insight into the pathogenesis of depression, development of biomarkers, and ultimately production of more effective depression therapies. METHOD: We reviewed several studies to evaluate contemporary concepts concerning proinflammatory cytokines and their relationship to various depressive disorders, the use of anti-inflammatory therapies in MDD treatment, and the application of neuroimaging in conjunction with cytokine profiles from both plasma and CSF as possible diagnostic tools. RESULTS: Proinflammatory cytokines in both plasma and CSF have been found to influence the progression and severity of depressive disorders in different populations. Studies have shown elevated serum levels of IL-1, IL-6, TNF-alpha, CRP, and MCP-1 in depressed patients, but have presented mixed results with IL-8 serum levels, and with IL-6 and MCP-1 CSF levels. Anti-inflammatory treatment of MDD may have adjuvant properties with current depression medications. MRI and NIRS neuroimaging confirm neurological abnormalities in the presence of elevated proinflammatory cytokines in depressed or stressed patients. LIMITATIONS: Heterogeneity of MDD and limited CSF cytokine research complicate the study of MDD pathogenesis. CONCLUSION: There is significant evidence that inflammatory processes influence the development and progression of MDD. Future studies with larger arrays of cytokine profiles aided by neuroimaging may provide more sensitive and specific modes of diagnostics in determining MDD etiology and provide guidance in individual therapies. PMID- 25128862 TI - Endogenous neurogenesis following ischaemic brain injury: insights for therapeutic strategies. AB - Ischaemic stroke is among the most common yet most intractable types of central nervous system (CNS) injury in the adult human population. In the acute stages of disease, neurons in the ischaemic lesion rapidly die and other neuronal populations in the ischaemic penumbra are vulnerable to secondary injury. Multiple parallel approaches are being investigated to develop neuroprotective, reparative and regenerative strategies for the treatment of stroke. Accumulating evidence indicates that cerebral ischaemia initiates an endogenous regenerative response within the adult brain that potentiates adult neurogenesis from populations of neural stem and progenitor cells. A major research focus has been to understand the cellular and molecular mechanisms that underlie the potentiation of adult neurogenesis and to appreciate how interventions designed to modulate these processes could enhance neural regeneration in the post ischaemic brain. In this review, we highlight recent advances over the last 5 years that help unravel the cellular and molecular mechanisms that potentiate endogenous neurogenesis following cerebral ischaemia and are dissecting the functional importance of this regenerative mechanism following brain injury. This article is part of a Directed Issue entitled: Regenerative Medicine: the challenge of translation. PMID- 25128863 TI - Simultaneous patterning of two different types of nanoparticles into alternating domains of a striped array of a polymer blend in a single spin-casting step. AB - A fast and convenient method is developed for simultaneously patterning inorganic nanoparticles with different optical, electronic or magnetic functionality to specific surface regions, by spin-casting onto microcontact printed substrates blend solutions in which the two nanoparticle types are functionalized with surface polymer brush layers of different surface energies. The process is based on phase separation of different nanoparticles based on their immiscible brush layers during spin-casting, with the underlying surface energy heterogeneity of the patterned substrate directing the different NP types to domains of different surface energies. Here, we specifically demonstrate the simultaneous localization of cadmium sulfide quantum dots (CdS QDs), addressed with a surface layer of polystyrene (PS), and silver nanoparticles (Ag NPs), addressed with a surface layer of poly(methyl methacrylate) (PMMA), onto the non-polar and polar surface domains, respectively, of hydrophilic glass patterned with hydrophobic octadecyltrichlorosilane (OTS) stripe arrays with micron-scale periodicities. In order to prevent gelation of solvent-swollen polymer-brush coated NPs during spin casting, which effects strong kinetic constraints on phase separation and localization, PS, PMMA or PS/PMMA homopolymer blends of sufficiently high Mw were added to the NP blends to increase the free volume between approaching NPs. The process parameters were fine-tuned to obtain control over defects in the obtained patterns. PMID- 25128865 TI - Phase transition of silica in the TMB-P123-H2O-TEOS quadru-component system: a feasible route to different mesostructured materials. AB - Various siliceous structures were obtained using a nonionic block copolymer (Pluronic P123) surfactant and trimethylbenzene (TMB) as a hydrophobic additive by hydrolysis and condensation of tetraethoxysilane (TEOS) in a sol-gel process. The resultant materials were characterized by small-angle X-ray diffraction (SAXRD), nitrogen adsorption analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results revealed the structure transformation from hexagonal structure (HEX) to multilamellar vesicles (MLVs) and then to mesocellular foams (MCFs) in the TMB-P123-H2O-TEOS quadru-component system. The morphology of the mesoporous silica was mainly controlled by the mass ratio of TMB/P123 resulted from the increasing volume of the hydrophobic chain of micelle of P123 that caused by more amount of TMB dissolved in the PPO segment of polymer. The fact that the occurrence of rod-like particles with curved ends and the coexistence of the MLVs and the HEX structure indicates that the MLVs are developed from the ends of HEX structures, rather than formed by a direct cooperative self-assembly mechanism. Further increasing of packing parameter of surfactant resulted from TMB addition transforms lamellar micelles to reversed micelles, leading to the formation of MCFs. PMID- 25128864 TI - (99m)Tc-labeled aminosilane-coated iron oxide nanoparticles for molecular imaging of alphanubeta3-mediated tumor expression and feasibility for hyperthermia treatment. AB - HYPOTHESIS: Dual-modality imaging agents, such as radiolabeled iron oxide nanoparticles (IO-NPs), are promising candidates for cancer diagnosis and therapy. We developed and evaluated aminosilane coated Fe3O4 (10+/-2nm) as a tumor imaging agent in nuclear medicine through 3-aminopropyltriethoxysilane (APTES) functionalization. We evaluated this multimeric system of targeted (99m)Tc-labeled nanoparticles (NPs) conjugated with a new RGD derivate (cRGDfK Orn3-CGG), characterized as NPs-RGD as a potential thermal therapy delivery vehicle. EXPERIMENTS: Transmission Electron Microscopy (TEM) and spectroscopy techniques were used to characterize the IO-NPs indicating their functionalization with peptides. Radiolabeled IO-NPs (targeted, non-targeted) were evaluated with regard to their radiochemical, radiobiological and imaging characteristics. In vivo studies were performed in normal and alphanubeta3 positive tumor (U87MG glioblastoma) bearing mice. We also demonstrated that this system could reach ablative temperatures in vivo. FINDINGS: Both radiolabeled IO NPs were obtained in high radiochemical yield (>98%) and proved stable in vitro. The in vivo studies for both IO-NPs have shown significant liver and spleen uptake at all examined time points in normal and U87MG glioblastoma tumor-bearing mice, due to their colloidal nature. We have confirmed through in vivo biodistribution studies that the non-targeted (99m)Tc-NPs poorly internalized in the tumor, while the targeted (99m)Tc-NPs-RGD, present 9-fold higher tumor accumulation at 1h p.i. Accumulation of both IO-NPs in other organs was negligible. Blocking experiments indicated target specificity for integrin receptors in U87MG glioblastoma cells. The preliminary in vivo study of applied alternating magnetic field showed that the induced hyperthermia is feasible due to the aid of IO-NPs. PMID- 25128866 TI - The prevalence of cognitive impairment in emergency general surgery. AB - OBJECTIVES: Rates of all surgical procedures are increasing at a faster rate than the population is ageing. However, this encouraging statistic, necessitates a robust evidence base. The epidemiological evidence base in acute general surgery in the older person is sparse. This is the first assessment of the prevalence of cognitive impairment measured using the Montreal Cognitive Assessment tool (MoCA) in acute general surgery. METHODS: In three sites in Wales, England and Scotland comprising rural and urban populations, we studied consecutive patients aged over 65 years. We considered any older person admitted to the acute general surgical unit. We assessed them for baseline demographic data. They each underwent a MoCA assessment. RESULTS: We collected data on 245 people, mean age 76.9 years (8.1, standard deviation), 136 (55.5%) were women. Of these 201 completed the MoCA test, mean score of 18.9 and median score 20 (range 0-30). There were 37 (15.1%) MoCA scores in the normal range (>=26) and 44 (18%) people were unable to attempt (or complete) the MoCA. Increasing age (p < 0.01) but not sex (p = 0.14) predicted an abnormal MoCA. Considering only the 44 people who were unable to attempt the MoCA assessment, 11 (25%) were known to have a diagnosis of dementia, 9 (20.5%) were too unwell and the remainder unable to complete the assessment to due pre-existing disability. CONCLUSIONS: In a representative UK wide population, a high proportion of older people admitted with an acute general surgical problem had cognitive impairment when assessed using the MoCA. PMID- 25128867 TI - Association of tissue inhibitor of metalloproteinase gene polymorphisms and unexplained recurrent spontaneous abortions in Han Chinese couples. AB - OBJECTIVE: To investigate the association of tissue inhibitor of metalloproteinase (TIMP) gene polymorphisms with unexplained recurrent spontaneous abortions (URSA) in a well-defined group of Han Chinese couples. STUDY DESIGN: This is a case-control association study. Genomic DNA was extracted from peripheral blood samples from 84 couples with histories of three or more pregnancy losses and 69 age-matched healthy couples with at least one live birth and no histories of pregnancy loss. Polymerase chain reactions (PCRs) and sequencing with the fluorescent dye dideoxy-termination method were used to detect the rs4898 in TIMP-1, rs2277698 in TIMP-2, rs2234921 and rs5749511 in TIMP 3 and rs17035945 in TIMP-4 genotypes and allele frequencies. RESULTS: Neither the allele frequencies nor any of the genetic model of the five TIMP gene SNPs (i.e., TIMP-1-rs4898, TIMP-2-rs2277698, TIMP-3-rs5749511 and rs2234921, and TIMP-4 rs7035945) were significantly differences between the URSA couples and the control group. CONCLUSIONS: No evidence was found for any associations between the TIMP-1,-2,-3, or -4 genes SNPs with URSA in this Han Chinese Han. PMID- 25128868 TI - Evaluation of carbon nanotubes and graphene as reinforcements for UHMWPE-based composites in arthroplastic applications: A review. AB - In this review we have evaluated the state of the art of CNT/UHMWPE and graphene/UHMWPE composites from four different points of view: mechanical properties, chemical stability, wear resistance and biocompatibility. The performance of these new carbonaceous composites allows us to conclude that these materials have overcome a first step on the way to developing into an alternative to the current HXLPEs used in orthopedic applications. PMID- 25128869 TI - From single fiber to macro-level mechanics: A structural finite-element model for elastomeric fibrous biomaterials. AB - In the present work, we demonstrate that the mesoscopic in-plane mechanical behavior of membrane elastomeric scaffolds can be simulated by replication of actual quantified fibrous geometries. Elastomeric electrospun polyurethane (ES PEUU) scaffolds, with and without particulate inclusions, were utilized. Simulations were developed from experimentally-derived fiber network geometries, based on a range of scaffold isotropic and anisotropic behaviors. These were chosen to evaluate the effects on macro-mechanics based on measurable geometric parameters such as fiber intersections, connectivity, orientation, and diameter. Simulations were conducted with only the fiber material model parameters adjusted to match the macro-level mechanical test data. Fiber model validation was performed at the microscopic level by individual fiber mechanical tests using AFM. Results demonstrated very good agreement to the experimental data, and revealed the formation of extended preferential fiber orientations spanning the entire model space. We speculate that these emergent structures may be responsible for the tissue-like macroscale behaviors observed in electrospun scaffolds. To conclude, the modeling approach has implications for (1) gaining insight on the intricate relationship between fabrication variables, structure, and mechanics to manufacture more functional devices/materials, (2) elucidating the effects of cell or particulate inclusions on global construct mechanics, and (3) fabricating better performing tissue surrogates that could recapitulate native tissue mechanics. PMID- 25128870 TI - Elastic softening of beta-type Ti-Nb alloys by indium (In) additions. AB - Recent developments showed that beta-type Ti-Nb alloys are good candidates for hard tissue replacement and repair. However, their elastic moduli are still to be further reduced to match Young's modulus values of human bone, in order to avoid stress shielding. In the present study, the effect of indium (In) additions on the structural characteristics and elastic modulus of Ti-40 Nb was investigated by experimental and theoretical (ab initio) methods. Several beta-type (Ti-40 Nb) xIn alloys (with x <= 5.2 wt%) were produced by cold-crucible casting and subsequent heat treatments (solid solutioning in the beta-field followed by water quenching). All studied alloys completely retain the beta-phase in the quenched condition. Room temperature mechanical tests revealed ultimate compressive strengths exceeding 770 MPa, large plastic strains (>20%) and a remarkable strain hardening. The addition of up to 5.2 wt% indium leads to a noticeable decrease of the elastic modulus from 69 GPa to 49 GPa, which is closer to that of cortical bone (<30 GPa). Young's modulus is closely related to the bcc lattice stability and bonding characteristics. The presence of In atoms softens the parent bcc crystal lattice, as reflected by a lower elastic modulus and reduced yield strength. Ab initio and XRD data agree that upon In substitution the bcc unit cell volume increases almost linearly. The bonding characteristics of In were studied in detail, focusing on the energies that appeared from the EDOSs significant for possible hybridizations. It came out that minor In additions introduce low energy states with s character that present antibonding features with the Ti first neighboring atoms as well as with the Ti-Nb second neighboring atoms thus weakening the chemical bonds and leading to elastic softening. These results could be of use in the design of low rigidity beta-type Ti-alloys with non-toxic additions, suitable for orthopedic applications. PMID- 25128872 TI - Sirtuin 3 interacts with Lon protease and regulates its acetylation status. AB - Lon is a mitochondrial protease that degrades oxidized damaged proteins, assists protein folding and participates in maintaining mitochondrial DNA levels. Changes in Lon mRNA levels, protein levels and activity are not always directly correlated, suggesting that Lon could be regulated at post translational level. We found that Lon and SIRT3, the most important mitochondrial sirtuin, colocalize and coimmunoprecipitate in breast cancer cells, and silencing or inhibition of Lon did not alter SIRT3 levels. Silencing of SIRT3 increased the levels of Lon protein and of its acetylation, suggesting that Lon is a target of SIRT3, likely at K917. PMID- 25128871 TI - Maternal emotional availability at bedtime and infant cortisol at 1 and 3 months. AB - BACKGROUND: Previous work has shown that early experience influences infant cortisol secretion. Few studies, however, have examined associations between parenting quality and cortisol levels and patterning in very young infants. AIMS: This study examined linkages between maternal emotional availability (EA) during a routine caregiving task, bedtime, and infant cortisol in the first 3 months of life. Concurrent and longitudinal associations between maternal EA and infant cortisol were examined. STUDY DESIGN: Families were visited when their infants were 1 and 3 months old. Video equipment was set up in order to record the infant's bedtime routine. Parents were provided with materials with which to take saliva samples from their infants at late afternoon, bedtime, and the following morning. SUBJECTS: At 1 month, participants were 96 mothers and infants living in a rural U.S. state. Data were available for 88 mothers and infants at 3 months. OUTCOME MEASURES: Maternal EA was scored from videotapes of bedtime at each age point. Infant cortisol was assessed from the saliva samples taken by parents. RESULTS: Regression analyses indicated that at 1 and 3 months of age, infants of more emotionally available mothers showed lower levels of cortisol secretion across the night than infants of less emotionally available mothers. Additionally, multilevel model analyses indicated that infants of more emotionally available mothers showed greater evidence of a decline in their cortisol levels across the evening, followed by an increase across the nighttime into the morning in their cortisol at 3 months. CONCLUSIONS: Findings suggest that maternal care in the context of a routine caregiving task is associated with lower stress reactivity and with earlier circadian patterning in very young infants. PMID- 25128873 TI - Analysis of (all-E)-lutein and its (Z)-isomers during illumination in a model system. AB - Light induced-isomerization of (all-E)-lutein in organic solvent and starch model systems was investigated. Lutein and its (Z)-isomers were separated by HPLC using a C30 column and gradient mobile phase based on methanol-methyl-tert-butyl ether water in 24min. (All-E)-lutein and twelve (Z)-isomers of lutein, in addition a small amount of (all-E)-zeaxanthin and (9Z, 9'Z)-zeaxanthin were identified by HPLC-DAD-APCI-MS. Five di-(Z)-luteins were identified for the first time, namely, (9Z, 9'Z)-, (9Z, 13Z)/(9 Z, 13'Z)-, (13Z, 15Z)- and (9Z, 15Z)-lutein and (9Z, 9'Z)-zeaxanthin. A mixture of (9Z)-lutein and of (9'Z)-lutein was the main product of the iodine-catalyzed photo-isomerization. (9Z, 13Z)/(9Z, 13'Z)-lutein were the major di-(Z)-isomers of lutein formed. The susceptibility of lutein to degradation was much less under dark storage than under lighted storage in starch model system. Isomerization and degradation of lutein and its (Z)-isomers proceeded simultaneously in all the model systems. PMID- 25128874 TI - Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR spectroscopy. AB - New analytical methods are needed to understand and optimize the processes by which tablets are produced. Fette 3090 tablet presses are commonly used in the pharmaceutical industry. A near-infrared (NIR) probe was installed into a Fette 3090 feed frame to understand and monitor the die filling process. The second objective was to analyze in detail the different factors that could affect the prediction of the developed NIR calibration models. Two monitoring positions for NIR spectrometers were evaluated; one at each side of the feed frame. A powder wave behavior caused by the paddle motion was observed inside the feed frame. The study also revealed that NIR spectra can help in the understanding of powder flow inside the feed frame. It was demonstrated that NIR spectra baselines can also be used to determine changes in mass inside the feed frame. The new NIR method showed that the paddle wheel speed has a significant impact in the powder dynamics inside the feed frame. The baselines of the NIR spectra depended on the mass hold-up inside the feed frame and paddle wheel speed. Studies using blends were performed to develop a NIR calibration model based on the feed frame system dynamics to determine acetaminophen drug concentration variability during the die filling process. The study found that variation in the distance from the powder to the probe due to paddle wheel speed has a significant effect on the NIR prediction. This study found that with NIR spectroscopy, blend uniformity can be assessed with high accuracy during the die filling process using the corresponding paddle wheel speed in-line calibration model. NIR was demonstrated to be a good development tool for the in-line monitoring of powder during the die filling process. PMID- 25128875 TI - UHPLC-MS/MS method for the determination of the cyclic depsipeptide mycotoxins beauvericin and enniatins in in vitro transdermal experiments. AB - Currently, dermal exposure data of cyclic depsipeptide mycotoxins beauvericin and enniatins are completely absent with a lack of local skin and systemic kinetics, despite their widespread skin contact and intrinsic hazard. Therefore a sensitive and specific bioanalytical high-throughput UHPLC-MS/MS method was developed for the quantitative and simultaneous determination of cyclic depsipeptide mycotoxins beauvericin and enniatins (A, A1, B, B1, D, E, C/F) in human skin Franz diffusion cell samples. The limits of detection ranged between 10 and 17pg/ml, while the total run time was only 4.5min. There was no significant effect of endogenous skin compounds on the mycotoxin MS signal observed, and the accuracy (0.68-24.68% bias) and precision (0.57-10.70% RSD) were considered acceptable for our purposes. Moreover, it was demonstrated that these cyclic depsipeptides are stable for at least 7 days when formulated in different organic or aqueous mixtures. Finally, adsorption to glass did occur: at least 50% ethanol or acetonitrile is required to prevent significant adsorption effects, which could be as high as 45%. PMID- 25128876 TI - Identification and quantification of antitumor thioproline and methylthioproline in Korean traditional foods by a liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. AB - A liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometric method (LC-APCI-MS/MS) has been developed for the sensitive determination of antitumor thioproline and methylthioproline from fermented foods. Thioproline and methylthioproline were derivatized in one step with ethyl chloroformate at room temperature. These compounds were identified and quantified in various traditional Korean fermented foods by LC-APCI-MS/MS. The concentration range of thioproline of each food was found for doenjang (0.011-0.032mg/kg), gochujang (0.010-0.038mg/kg), and ganjang (0.010-0.038mg/kg). Those of methylthioproline of each food was found for doenjang (0.098-0.632mg/kg), gochujang (0.015-0.112mg/kg), and ganjang (0.023-1.468mg/kg). A prolonged aging time leads to an increase in both the thioproline and methylthioproline contents, suggesting that the storage time plays a key role in the formation of thioproline and methylthioproline in Korean traditional foods. The results here suggest that thioproline and methylthioproline are related to the biological activities of traditional Korean fermented foods. PMID- 25128877 TI - Acute exercise improves motor memory: exploring potential biomarkers. AB - We have recently shown that a single bout of acute cardiovascular exercise improves motor skill learning through an optimization of long-term motor memory. Here we expand this previous finding, to explore potential exercise-related biomarkers and their association with measures of motor memory and skill acquisition. Thirty-two healthy young male subjects were randomly allocated into either an exercise or control group. Following either an intense bout of cycling or rest subjects practiced a visuomotor tracking task. Motor skill acquisition was assessed during practice and retention 1 h, 24 h and 7 days after practice. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), epinephrine, norepinephrine, dopamine and lactate were analyzed at baseline, immediately after exercise or rest and during motor practice. The exercise group showed significantly better skill retention 24h and 7 days after acquisition. The concentration of all blood compounds increased significantly immediately after exercise and remained significantly elevated for 15 min following exercise except for BDNF and VEGF. Higher concentrations of norepinephrine and lactate immediately after exercise were associated with better acquisition. Higher concentrations of BDNF correlated with better retention 1 h and 7 days after practice. Similarly, higher concentrations of norepinephrine were associated with better retention 7 days after practice whereas lactate correlated with better retention 1h as well as 24 h and 7 days after practice. Thus, improvements in motor skill acquisition and retention induced by acute cardiovascular exercise are associated with increased concentrations of biomarkers involved in memory and learning processes. More mechanistic studies are required to elucidate the specific role of each biomarker in the formation of motor memory. PMID- 25128878 TI - Learning pain-related fear: neural mechanisms mediating rapid differential conditioning, extinction and reinstatement processes in human visceral pain. AB - BACKGROUND AND AIMS: There exists converging evidence to support a role of pain related fear in the pathophysiology and treatment of chronic pain conditions. Pain-related fear is shaped by associative learning and memory processes, which remain poorly characterized especially in the context of abdominal pain such as in irritable bowel syndrome (IBS). Therefore, using event-related functional magnetic resonance imaging (fMRI), we assessed the neural mechanisms mediating the formation, extinction and reinstatement of abdominal pain-related fear in healthy humans. Employing painful rectal distensions as clinically-relevant unconditioned stimuli (US), in this fear conditioning study we tested if differential excitatory and inhibitory learning is evocable after very few CS-US learning trials ("rapid conditioning"), and explored the underlying neural substrates of these learning and memory processes. METHODS: In N=24 healthy men and women, "rapid" fear acquisition was accomplished by pairing visual conditioned stimuli (CS(+)) with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS(-)) were presented without US (differential delay conditioning with five CS(+) and five CS(-) presentations and a 80% reinforcement ratio). During extinction, all CS were presented without US. Subsequently, a reinstatement procedure was implemented, defined as the retrieval of an extinguished memory after unexpected and unpaired exposure to the US, followed by CS presentations. For each phase, changes in perceived CS-US contingency and CS unpleasantness were assessed with visual analogue scales and compared with analyses of variance. fMRI data were analyzed using whole-brain analyses (at p<.001 uncorrected) and in regions-of-interest analyses with familywise error correction of alpha (pFWE<.05). Differential neural activation in response to the CS during each experimental phase (i.e., CS(+)>CS(-); CS(+)7.5 L/kg), suggesting that CNTs can act as strong sorbents under a wide range of conditions. PMID- 25128884 TI - Accuracy of mixing models in predicting sediment source contributions. AB - Determining the source of sediment using geochemical properties is now a widely used approach in catchment management. However the outcome of these studies often depends on the type of model used to determine the relative contribution from difference sources. Here we test the accuracy and robustness of four widely used sediment mixing models using artificial mixtures of three well-distinguished geologic sources. Sub-samples from these three sources were mixed to create four groups of samples, each consisting of five samples, with known source contributions, 20 samples in total. The source contributions to the individual and groups of artificial sediment mixtures were calculated using each of the four mixing models: Modified Hughes, Modified Collins, Landwehr and Distribution models. Unlike Modified Collins and Landwehr models which use calculated values from each tracer property of individual sources (e.g. mean and standard deviation), Hughes model uses the measured fingerprint property of replicated samples from each source and Distribution model incorporate distribution of tracers and correlation between tracer properties for sediment samples and sources. For the 20 individual sample mixtures the Distribution model provided the closest estimates to the known sediment source contribution values (Mean Absolute Error (MAE)=10.8%, and standard error (SE)=0.9%). The Modified Hughes (MAE=13.5%, SE=1.1%), Landwehr (MAE=19%, SE=1.7) and Collins models (MAE=29%, SE=2.1%) were the next accurate models, respectively. For the groups of the samples the Modified Hughes was the most robust source contribution predictor with 5.4% error. The Distribution model (MAE=6.1%) and Landwehr model (MAE=7.8%) were the second and third accurate models. Collins model with MAE of 28.3% was a significantly weaker source contribution predictor than the three other models. This study demonstrates the dependence of source attribution on model selection. The study highlight the need to test mixing model using known source and mixture samples prior to applying them to field samples. The results indicate that the Distribution and Modified Hughes models provided the most accurate source attributions using geochemical fingerprint properties. PMID- 25128885 TI - Evaluation of the transfer of soil arsenic to maize crops in suburban areas of San Luis Potosi, Mexico. AB - The presence of arsenic (As) in agricultural food products is a matter of concern because it can cause adverse health effects at low concentrations. Agricultural product intake constitutes a principal source for As exposure in humans. In this study, the contribution of the chemical-soil parameters in As accumulation and translocation in the maize crop from a mining area of San Luis Potosi was evaluated. The total arsenic concentration and arsenic speciation were determined by HG-AFS and IC-HG-AFS, respectively. The data analysis was conducted by cluster analysis (CA) and principal component analysis (PCA). The soil pH presented a negative correlation with the accumulated As in each maize plant part, and parameters such as iron (Fe) and manganese (Mn) presented a higher correlation with the As translocation in maize. Thus, the metabolic stress in maize may induce organic acid exudation leading a higher As bioavailability. A high As inorganic/organic ratio in edible maize plant tissues suggests a substantial risk of poisoning by this metalloid. Careful attention to the chemical changes in the rhizosphere of the agricultural zones that can affect As transfer through the food chain could reduce the As-intoxication risk of maize consumers. PMID- 25128886 TI - Estimation of uncertainty in the sampling and analysis of polychlorinated biphenyls and polycyclic aromatic hydrocarbons from contaminated soil in Brighton, UK. AB - The heterogeneity of environmental samples is increasingly recognised, yet rarely examined in organic contamination investigations. In this study soil samples from an ex-landfill site in Brighton, UK were analysed for polychlorinated biphenyl (PCB) and polycyclic aromatic hydrocarbon (PAH) contamination by using a balanced sampling protocol. The analytical technique of gas chromatography-mass spectrometry was found to be fit for purpose by the use of duplicate samples and the statistical analysis of variances, as well as of certified reference materials. The sampling uncertainty was found to significantly overweigh the analytical uncertainty, by a factor of 3 and 6 for PCBs and PAHs, respectively. The soil samples showed a general trend of PCB concentration that was under the recommended target level of 20 ng/g dry weight. It is possible that one site alongside the main road may exceed the 20 ng/g target level, after taking into consideration the overall measurement uncertainty (70.8%). The PAH contamination was more severe, with seven sites potentially exceeding the effect-range medium concentrations. The soil samples with relatively high PCB and PAH concentrations were all taken from the grass verge, which also had the highest soil organic carbon content. The measurement uncertainty which was largely due to sampling can be reduced by sampling at a high resolution spacing of 17 m, which is recommended in future field investigations of soil organic contamination. PMID- 25128887 TI - Farmer and retailer knowledge and awareness of the risks from pesticide use: a case study in the Wei River catchment, China. AB - Monitoring the educational level of farmers and retailers on pesticide use would be useful to assess the appropriateness of information for reducing or/and avoiding the risks from pesticides in rural regions. The levels of knowledge and awareness of the dangers to the environment and human health were investigated by questionnaires for farmers (209) and retailers (20) in two rural regions (Qianyang County (S1) and Chencang County (S2)) of the Wei River catchment in China where the modes of farming and the state of erosion are very different. The results showed that farmers learned the use and dangers of pesticides mainly by oral communication (p<0.01). Protective measures were inadequate; 65% (S1) and 55% (S2) of farmers never used any protective measures during spraying (p<0.05). Washing hands (>70%) was the most common mode of personal hygiene, relative to wearing masks, showering, and changing clothes, but no significant differences were observed between the selected regions. Most pesticide wastes were dumped directly onto the land or into water, suggesting that educational measures should be taken to address the potential risks from the residues in the wastes. Over 85% of farmers (S1 and S2) claimed to use illegal pesticides, but the reasons for their use varied (p<0.01). Retailers were well-informed and highly conscious of their responsibility for the safe use of pesticides, especially in S2 (p<0.01). A canonical correspondence analysis indicated that educational level and age differed between the two regions and contributed greatly to the risks from pesticide use (p<0.01). Educational programmes targeted to age groups, proper disposal of pesticide waste, and sufficient supervision from authorities should consequently be considered for improving the levels of knowledge and awareness of the dangers of pesticides to human health and environmental pollution in the Wei River catchment, China. PMID- 25128888 TI - Occurrence of antibiotics in the aquatic environment of Jianghan Plain, central China. AB - The occurrence of 19 antibiotics (sulfonamide, fluoroquinolone, tetracycline and macrolide) was studied in surface water and groundwater samples collected from Shahu County of Jianghan Plain, central China, in autumn (dry season) and spring (wet season). In autumn, chlorotetracycline, doxycycline and enrofloxacin were the three antibiotics with the highest concentrations and high relevance ratios in all of the water samples. The concentration of chlorotetracycline was greatest in surface water at 122.3 n gL(-1) and was as high as 86.6 ng L(-1) in groundwater, which are among the highest values reported worldwide. In spring, tetracycline was found to be more than 100 ng L(-1) in groundwater and surface water, which also contained high concentrations of ofloxacin (135.1 ng L(-1)), norfloxacin (134.2 ng L(-1)) and erythromycin dehydrate (381.5 ng L(-1)). Most of the SMs were observed at higher detection frequencies in spring than in autumn, which can be ascribed to surface runoff by rain water during the wet season (spring). The average concentrations of compounds in the fluoroquinolone and tetracycline categories were far higher than those in the sulfonamide and macrolide categories, which had concentrations of less than 16 ng L(-1) in groundwater (except erythromycin dehydrate), while macrolides were found in all samples, except erythromycin dehydrate. The main antibiotics present in groundwater were also the dominant compounds found in surface water, with correlation coefficients of 0.93 and 0.97 in autumn and spring, respectively, indicating the potential contamination of groundwater by the infiltration of contaminated surface water. PMID- 25128889 TI - Fluorine distribution in soil in the vicinity of an accidental spillage of hydrofluoric acid in Korea. AB - This study assessed the status of fluorine (F) in soil in the vicinity of a spillage of anhydrous hydrofluoric acid in Korea. Gaseous hydrogen fluoride dispersed was suspected to have contaminated the surrounding soil environment. Total and water soluble F concentrations in soil within a 1 km radius of the spillage were determined. Total F concentrations (mean=222+/-70.1 mg kg(-1)) were lower than the Korean limit value (i.e., 400 mg kg(-1)) and several reported measurements of background F concentrations in soils except for a single outlying case. Soluble F concentrations ranged from 0.111 to 6.40 mg kg(-1) (mean=2.20+/ 1.80 mg kg(-1)). A negative correlation between the soluble F concentration of soil and distance from the spillage was observed. This indicates that the soluble F concentration has a crucial role in fractionating the F concentration arising from a 'non natural input' i.e., the spillage. The F content of rice samples seemed to be significantly influenced by the soluble F concentrations of soils. Rice samples collected from the control and affected areas contained 41 mg kg(-1) and 578 mg kg(-1) of total F, respectively. PMID- 25128890 TI - Stereoselective quantitation of haloxyfop in environment samples and enantioselective degradation in soils. AB - The chiral separation of haloxyfop enantiomers was first performed on (R, R) Whelk-O1 chiral column (pirkle type) by high-performance liquid chromatography (HPLC). Chromatographic conditions such as mobile phase composition and column temperature were optimized, and the best resolution was obtained using hexane/n propanol (98/2) with Rs value of 3.43. Chiral residue analysis methods for haloxyfop enantiomers in environmental matrices, such as soil and water, were developed with recoveries ranging from 85.95% to 104.25%. The results showed that these methods were effective enough for detecting the residual enantiomers environmental matrices. The behavior of haloxyfop in four soils was studied and the enantioselective degradation was found with enantiomer fraction values ranging from 0.058 to 0.61. The research work was extremely useful for investigating the fate of individual enantiomers in environment, the mechanism of the stereoselective behaviors, and the risk assessment of chiral pesticide. PMID- 25128891 TI - Interaction mechanisms between organic UV filters and bovine serum albumin as determined by comprehensive spectroscopy exploration and molecular docking. AB - Organic UV filters are a group of emerging PPCP (pharmaceuticals and personal care products) contaminants. Current information is insufficient to understand the in vivo processes and health risks of organic UV filters in humans. The interaction mechanism of UV filters with serum albumin provides critical information for the health risk assessment of these active ingredients in sunscreen products. This study investigates the interaction mechanisms of five commonly used UV filters (2-hydroxy-4-methoxybenzophenone, BP-3; 2-ethylhexyl 4 methoxycinnamate, EHMC; 4-methylbenzylidene camphor, 4-MBC; methoxydibenzoylmethane, BDM; homosalate, HMS) with bovine serum albumin (BSA) by spectroscopic measurements of fluorescence, circular dichroism (CD), competitive binding experiments and molecular docking. Our results indicated that the fluorescence of BSA was quenched by these UV filters through a static quenching mechanism. The values of the binding constant (Ka) ranged from (0.78+/ 0.02)*10(3) to (1.29+/-0.01)*10(5) L mol(-1). Further exploration by synchronous fluorescence and CD showed that the conformation of BSA was demonstrably changed in the presence of these organic UV filters. It was confirmed that the UV filters can disrupt the alpha-helical stability of BSA. Moreover, the results of molecular docking revealed that the UV filter molecule is located in site II (sub domain IIIA) of BSA, which was further confirmed by the results of competitive binding experiments. In addition, binding occurred mainly through hydrogen bonding and hydrophobic interaction. This study raises critical concerns regarding the transportation, distribution and toxicity effects of organic UV filters in human body. PMID- 25128892 TI - Photochemical transformation of phenylurea herbicides in surface waters: a model assessment of persistence, and implications for the possible generation of hazardous intermediates. AB - This work models the phototransformation kinetics in surface waters of five phenylurea herbicides (diuron, fenuron, isoproturon, metoxuron and chlortoluron), for which important photochemical parameters are available in the literature (direct photolysis quantum yields and reaction rate constants with .OH, CO3(-.) and the triplet states of chromophoric dissolved organic matter, (3)CDOM*). Model calculations suggest that isoproturon and metoxuron would be the least photochemically persistent and diuron the most persistent compound. Reactions with .OH and (3)CDOM* would be the main phototransformation pathways for all compounds in the majority of environmental conditions. Reaction with CO3(-) could be important in waters with low dissolved organic carbon (DOC), while direct photolysis would be negligible for fenuron, quite important for chlortoluron, and somewhat significant for the other compounds. The direct photolysis of metoxuron and diuron is known to increase toxicity, and such a photoreaction pathway would be enhanced at intermediate DOC values (1-4 mg C L(1)). The reaction between phenylureas and .OH is known to produce toxic intermediates, differently from (3)CDOM*. Therefore, the shift of reactivity from .OH to (3)CDOM* with increasing DOC could reduce the environmental impact of photochemical transformation. PMID- 25128893 TI - Engineered nanoparticles and organic matter: a review of the state-of-the-art. AB - Growth in the development and production of engineered nanoparticles (ENPs) in recent years has increased the potential for interactions of these nanomaterials with aquatic and terrestrial environments. Carefully designed studies are therefore required in order to understand the fate, transport, stability, and toxicity of nanoparticles. Natural organic matter (NOM), such as the humic substances found in water, sediment, and soil, is one of the substances capable of interacting with ENPs. This review presents the findings of studies of the interaction of ENPs and NOM, and the possible effects on nanoparticle stability and the toxicity of these materials in the environment. In addition, ENPs and NOM are utilized for many different purposes, including the removal of metals and organic compounds from effluents, and the development of new electronic sensors and other devices for the detection of active substances. Discussion is therefore provided of some of the ways in which NOM can be used in the production of nanoparticles. Although there has been an increase in the number of studies in this area, further progress is needed to improve understanding of the dynamic interactions between ENPs and NOM. PMID- 25128894 TI - Sensitive amperometric determination of methimazole based on the electrocatalytic effect of rutin/multi-walled carbon nanotube film. AB - Electrochemical deposition was used to prepare a glassy carbon electrode modified with multi-walled carbon nanotubes and the glycosidic compound, rutin (R/MWCNTs/GCE). Cyclic voltammetry of the modified electrode in aqueous solution (pH8) showed a pair of well-defined, stable and reversible redox peaks with surface confined characteristics. The catechol moiety of rutin produced the voltammetric peaks via a 2 electron, 2 proton mechanism in the range of 0.0-0.4V (vs. Ag/AgCl). The transfer coefficient (alpha), heterogeneous electron transfer rate constant (ks), and surface concentration (Gamma) for R/MWCNTs/GCE were calculated by using the cyclic voltammetric data. The modified electrode showed excellent catalytic activity toward oxidation of methimazole. Fixed-potential amperometry was used for sub-micromolar determination of methimazole at pH8. Linear dependence of anodic current to methimazole concentration was obtained in the range of 0.1-26MUM of the drug with a limit of detection at 18nM. The modified electrode retained its initial response for at least 2weeks if stored in dry ambient conditions. The electrode was used for the amperometric determination of methimazole in formulations and spiked blood serum samples, successfully. PMID- 25128895 TI - Nano-cerium vanadate: a novel inorganic ion exchanger for removal of americium and uranium from simulated aqueous nuclear waste. AB - Cerium vanadate nanopowders were synthesized by a facile low temperature co precipitation method. The product was characterized by X-ray diffraction and transmission electron microscopy and found to consist of ~25 nm spherical nanoparticles. The efficiency of these nanopowders for uptake of alpha-emitting radionuclides (233)U (4.82 MeV alpha) and (241)Am (5.49 MeV alpha, 60 keV gamma) has been investigated. Thermodynamically and kinetically favorable uptake of these radionuclides resulted in their complete removal within 3h from aqueous acidic feed solutions. The uptake capacity was observed to increase with increase in pH as the zeta potential value decreased with the increase in pH but effect of ionic strength was insignificant. Little influence of the ions like Sr(2+), Ru(3+), Fe(3+), etc., in the uptake process indicated CeVO4 nanopowders to be amenable for practical applications. The isotherms indicated predominant uptake of the radioactive metal ions in the solid phase of the exchanger at lower feed concentrations and linear Kielland plots with positive slopes indicated favorable exchange of the metal ions with the nanopowder. Performance comparison with the other sorbents reported indicated excellent potential of nano-cerium vanadate for removing americium and uranium from large volumes of aqueous acidic solutions. PMID- 25128896 TI - Removal of trace mercury(II) from aqueous solution by in situ formed Mn-Fe (hydr)oxides. AB - The efficiency and mechanism of trace mercury (Hg(II)) removal by in situ formed manganese-ferric (hydr)oxides (in situ Mn-Fe) were investigated by reacting KMnO4 with Fe(II) in simulated solutions and natural water. In the simulated solutions, the impact of coagulant dosage, pH, and temperature on mercury removal was studied. Experimental results showed that in situ Mn-Fe more effectively removed mercury compared with polyaluminum chloride (PAC) and iron(III) chloride (FeCl3), and that mercury existed in the form of uncharged species, namely Hg(OH)2, HgClOH(aq), and HgCl2(aq). Fourier transform infrared spectroscopy demonstrated that in situ Mn-Fe contained hydroxyl groups as the surface active sites, while X ray photoelectron spectroscopy (XPS) measurements revealed that MnO2 or MnOOH and FeOOH were the dominant species in the precipitates. XPS analysis indicated that an Hg-Mn-Fe mixture was formed in the precipitates, suggesting that mercury was removed from solutions via transfer from the liquid phase to solid phase. These results indicated that the primary mercury removal mechanisms in in situ Mn-Fe were surface complexation and flocculation-precipitation processes. Satisfactory removal efficiency of mercury was also observed following in situ Mn-Fe in natural waters. PMID- 25128897 TI - Influenza virus-like particle vaccines made in Nicotiana benthamiana elicit durable, poly-functional and cross-reactive T cell responses to influenza HA antigens. AB - Cell-mediated immunity plays a major role in long-lived, cross-reactive protection against influenza virus. We measured long-term poly-functional and cross-reactive T cell responses to influenza hemagglutinin (HA) elicited by a new plant-made Virus-Like Particle (VLP) vaccine targeting either H1N1 A/California/7/09 (H1) or H5N1 A/Indonesia/5/05 (H5). In two independent clinical trials, we characterized the CD4(+) and CD8(+) T cell homotypic and heterotypic responses 6 months after different vaccination regimens. Responses of VLP vaccinated subjects were compared with placebo and/or a commercial trivalent inactivated vaccine (TIV:FluzoneTM) recipients. Both H1 and H5 VLP vaccines elicited significantly greater poly-functional CD4(+) T cell responses than placebo and TIV. Poly-functional CD8(+) T cell responses were also observed after H1 VLP vaccination. Our results show that plant-made HA VLP vaccines elicit both strong antibody responses and poly-functional, cross-reactive memory T cells that persist for at least 6 months after vaccination. PMID- 25128898 TI - A dorsal-pathway account of aphasic language production: the WEAVER++/ARC model. AB - It has long been assumed that a dorsal pathway running from temporal to inferior frontal cortex underpinned by the left arcuate fasciculus (AF) underlies both repetition and spoken language production. However, according to a recent proposal, a ventral pathway underpinned by extreme capsule (EmC) and uncinate fasciculus (UF) fiber tracts is primarily responsible for language production, whereas the AF primarily underlies repetition. Here, a computational implementation of the dorsal-pathway account of language production is presented, called WEAVER++/ARC (for WEAVER++ Arcuate Repetition and Conversation), which synthesizes behavioral psycholinguistic, functional neuroimaging, and tractographic evidence. The results of computer simulations revealed that the model accounts for the typical patterns of impaired and spared language performance associated with classic acute-onset and progressive aphasias. Moreover, the model accounts for recent evidence that damage to the AF but not the EmC/UF pathway predicts impaired production performance. It is concluded that the results demonstrate the viability of a dorsal-pathway account of language production. PMID- 25128900 TI - Mangostanaxanthones I and II, new xanthones from the pericarp of Garcinia mangostana. AB - Two new xanthones: mangostanaxanthones I (3) and II (5) were isolated from the pericarp of Garcinia mangostana, along with four known xanthones: 9 hydroxycalabaxanthone (1), parvifolixanthone C (2), alpha-mangostin (4), and rubraxanthone (6). Their structures were elucidated on the basis of IR, UV, 1D, 2D NMR, and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their antioxidant, antimicrobial, and quorum-sensing inhibitory activities. Compounds 3 and 5 displayed promising antioxidant activity with IC50 12.07 and 14.12 MUM, respectively using DPPH assay. Compounds 4-6 had weak to moderate activity against Escherichia coli and Staphylococcus aureus, while demonstrated promising action against Bacillus cereus with MICs 0.25, 1.0, and 1.0mg/mL, respectively. The tested compounds were inactive against Candida albicans. However, they showed selective antifungal potential toward Aspergillus fumigatus. Compounds 3 and 4 possessed quorum sensing inhibitory activity against Chromobacterium violaceum ATCC 12472. PMID- 25128899 TI - Molecular aspects of tight junction barrier function. AB - In complex multicellular organisms, epithelia lining body cavities regulate absorption and secretion of ions, organic molecules, and water. Proper function of epithelia depends on apically and basolaterally situated ion channels as well as tight junctions which seal the apical intercellular space. Without tight junctions, transepithelial concentration gradients of ions and nutrients would be dissipated through the paracellular space. Elevated tight junction permeability is a feature of many diseases of multiple organs, including the gastrointestinal tract [1,2,3(*),4(*)], kidney [5,6], and lungs [7,8]. In the intestines, epithelial barrier dysfunction is a major contributor to diarrhea and malnutrition and is associated with significant morbidity and mortality worldwide. PMID- 25128901 TI - Biphenyls from Nicotiana tabacum and their anti-tobacco mosaic virus. AB - Five new biphenyls, tababiphenyls A-E (1-5), together with five known ones (5 10), were isolated from the leaves of Nicotiana tabacum, of which compound 1 possessed a seldom reported 6-carbons unit in biphenyls. Their structures were established on the basis of extensive spectroscopic analyses. All compounds were tested for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compounds 3 and 5 exhibited high anti-TMV activities with inhibition rate of 48.4% and 32.1%, respectively, which were higher than that of positive control (ningnanmycin). The other compounds also showed potential anti-TMV activities with inhibition rates in the range of 18.6-28.7%, respectively. PMID- 25128902 TI - Investigating driver willingness to drive through flooded waterways. AB - Approximately 40% of all drowning deaths involve a motor vehicle. Regardless of its significance as a cause of flood-related mortality, there is continued prevalence of driving through flooded waterways in Australia and worldwide. We aimed to understand the motivational determinates of driving through flooded waterways in low and high-risk scenarios by utilizing an augmented theory of planned behaviour (TPB) with behavioural willingness as the outcome variable as well as the influence of additional predictors; namely perceived risk and past behaviour. Participants (n=174; Mage=27.43, SD=10.76) answered standard TPB-based questions in regards to attitudes, subjective norm, and perceived behavioural control (PBC), as well as additional variables of perceived risk (i.e., perceived susceptibility and perceived severity) and past behaviour. Support was found for the augmented TPB as attitude, subjective norm, and PBC predicted behavioural willingness. Support was also found for perceived severity in the high-risk but not the low-risk scenario. No support was found for perceived susceptibility. Past behaviour emerged as a significant predictor of willingness in the low and high-risk scenario. The findings provide support for an augmented TPB in understanding individuals' willingness to drive through flooded waterways, suggesting that a multi-strategy approach may be critical in attempts to reduce the incidence of such risky driving behaviour. PMID- 25128903 TI - A human experimental model of episodic pain. AB - An experimental model of daily episodic pain was developed to investigate peripheral sensitization and cortical reorganization in healthy individuals. Two experiments (A and B) were conducted. Experiments A and B consisted of one and five consecutive days, respectively, in which the participants were subjected to 45 min of intense painful cutaneous electrical stimulation (episodic pain session), using a stimulus paradigm that in animals has been shown to induce long term potentiation. These electrical stimulations produced a verbal pain rating of approximately 85 on a 0-100 verbal rating scale (VRS). Physiological (blood flow and axon flare reflex), psychophysical (perception threshold and verbal pain ratings) and electrophysiological (128 channels recorded somatosensory evoked potential (SEP)) measurements were recorded. The stimulation evoked a visible axon flare reflex and caused significantly increased cutaneous blood flow around the site of the stimulation. Axon flare reflex and blood flow reached a plateau on day one in all the subjects and no significant changes between the days were observed. The results showed that the effect of the electrical stimulations changed over the five days; pain potentiation was induced on the first day (significant increase in the verbal pain ratings during the 45 min stimulation) but not on any of the subsequent days. After five days of subsequent pain induction, the global field power showed a significant reduction in P2 amplitude in the late stage (200-370 ms, in the central-parietal area). In conclusion, the results suggest that in healthy individuals this model of episodic pain produces a rapid adaptation after day one and that generates significant SEP changes at day five. PMID- 25128905 TI - Fusing transcriptomics to progressive prostate cancer. AB - This commentary highlights the article by Yu et al, describing a set of novel fusion transcripts strongly associated with prostate cancer prognosis. PMID- 25128904 TI - Phoneme-free prosodic representations are involved in pre-lexical and lexical neurobiological mechanisms underlying spoken word processing. AB - Recently we reported that spoken stressed and unstressed primes differently modulate Event Related Potentials (ERPs) of spoken initially stressed targets. ERP stress priming was independent of prime-target phoneme overlap. Here we test whether phoneme-free ERP stress priming involves the lexicon. We used German target words with the same onset phonemes but different onset stress, such as MANdel ("almond") and manDAT ("mandate"; capital letters indicate stress). First syllables of those words served as primes. We orthogonally varied prime-target overlap in stress and phonemes. ERP stress priming did neither interact with phoneme priming nor with the stress pattern of the targets. However, polarity of ERP stress priming was reversed to that previously obtained. The present results are evidence for phoneme-free prosodic processing at the lexical level. Together with the previous results they reveal that phoneme-free prosodic representations at the pre-lexical and lexical level are recruited by neurobiological spoken word recognition. PMID- 25128908 TI - MRI criteria for the diagnosis of pleomorphic adenoma: a validation study. AB - OBJECTIVES: To validate an MRI algorithm characteristic of pleomorphic adenoma (PA). STUDY DESIGN: Cross-sectional analysis. SETTING: Academic tertiary-care medical center. METHODS: A radiologic algorithm for the MRI diagnosis of PA was developed on the basis of five "high probability" criteria that all must be fulfilled for the MRI to qualify as a positive test result: bright T2-signal, sharp margins, heterogeneous nodular enhancement, lobulated contours, T2-dark rim. We then identified MRI images from our institutional database to test the diagnostic accuracy of the proposed algorithm. RESULTS: A total of 103 parotidectomy cases with adequate MRI studies were identified (pleomorphic adenoma n=41, mucoepidermoid carcinoma n=11, Warthin's tumor n=8, adenoid cystic carcinoma n=6, oncocytoma n=6, acinic cell carcinoma n=5, salivary duct carcinoma n=5, and other n=21). Eighteen of 21 cases that met all five "high probability" MRI criteria were consistent with PA on final histopathology; 3 were consistent with carcinoma. MRI had a specificity of 95.1% [95% confidence interval: 85.6 98.7%] and sensitivity of 43.9% [95% C.I.: 28.8-60.1%] for PA. The positive predictive value was 85.7% [95% C.I.: 70.4-100%] and the negative predictive value was 71.9% [95% C. I.: 62.0-81.9%]. The overall diagnostic accuracy was 74.8% [95% C.I.: 66.2-83.3%]. CONCLUSION: A "high probability" MRI is about 95% specific for pleomorphic adenoma. A subset of patients with MRI imaging that is highly suggestive of PA may reliably avoid further workup. The value of MRI in this setting is especially useful if preoperative fine needle aspiration is not readily available. A significant proportion of PAs, however, have indeterminate imaging features that overlap considerably with other benign and malignant lesions. PMID- 25128906 TI - Lung cancer transcriptomes refined with laser capture microdissection. AB - We evaluated the importance of tumor cell selection for generating gene signatures in non-small cell lung cancer. Tumor and nontumor tissue from macroscopically dissected (Macro) surgical specimens (31 pairs from 32 subjects) was homogenized, extracted, amplified, and hybridized to microarrays. Adjacent scout sections were histologically mapped; sets of approximately 1000 tumor cells and nontumor cells (alveolar or bronchial) were procured by laser capture microdissection (LCM). Within histological strata, LCM and Macro specimens exhibited approximately 67% to 80% nonoverlap in differentially expressed (DE) genes. In a representative subset, LCM uniquely identified 300 DE genes in tumor versus nontumor specimens, largely attributable to cell selection; 382 DE genes were common to Macro, Macro with preamplification, and LCM platforms. RT-qPCR validation in a 33-gene subset was confirmatory (rho = 0.789 to 0.964, P = 0.0013 to 0.0028). Pathway analysis of LCM data suggested alterations in known cancer pathways (cell growth, death, movement, cycle, and signaling components), among others (eg, immune, inflammatory). A unique nine-gene LCM signature had higher tumor-nontumor discriminatory accuracy (100%) than the corresponding Macro signature (87%). Comparison with Cancer Genome Atlas data sets (based on homogenized Macro tissue) revealed both substantial overlap and important differences from LCM specimen results. Thus, cell selection via LCM enhances expression profiling precision, and confirms both known and under-appreciated lung cancer genes and pathways. PMID- 25128907 TI - Re-testing and misclassification of HIV-2 and HIV-1&2 dually reactive patients among the HIV-2 cohort of the West African Database to evaluate AIDS collaboration. AB - INTRODUCTION: West Africa is characterized by the circulation of HIV-1 and HIV-2. The laboratory diagnosis of these two infections as well as the choice of a first line antiretroviral therapy (ART) is challenging, considering the limited access to second-line regimens. This study aimed at confirming the classification of HIV 2 and HIV-1&2 dually reactive patients followed up in the HIV-2 cohort of the West African Database to evaluate AIDS collaboration. METHOD: A cross-sectional survey was conducted from March to December 2012 in Burkina Faso, Cote d'Ivoire and Mali among patients classified as HIV-2 or HIV-1&2 dually reactive according to the national HIV testing algorithms. A 5-ml blood sample was collected from each patient and tested in a single reference laboratory in Cote d'Ivoire (CeDReS, Abidjan) with two immuno-enzymatic tests: ImmunoCombII(r) (HIV-1&2 ImmunoComb BiSpot - Alere) and an in-house ELISA test, approved by the French National AIDS and hepatitis Research Agency (ANRS). RESULTS: A total of 547 patients were included; 57% of them were initially classified as HIV-2 and 43% as HIV-1&2 dually reactive. Half of the patients had CD4>=500 cells/mm(3) and 68.6% were on ART. Of the 312 patients initially classified as HIV-2, 267 (85.7%) were confirmed as HIV-2 with ImmunoCombII(r) and in-house ELISA while 16 (5.1%) and 9 (2.9%) were reclassified as HIV-1 and HIV-1&2, respectively (Kappa=0.69; p<0.001). Among the 235 patients initially classified as HIV-1&2 dually reactive, only 54 (23.0%) were confirmed as dually reactive with ImmunoCombII(r) and in house ELISA, while 103 (43.8%) and 33 (14.0%) were reclassified as HIV-1 and HIV 2 mono-infected, respectively (kappa= 0.70; p<0.001). Overall, 300 samples (54.8%) were concordantly classified as HIV-2, 63 (11.5%) as HIV-1&2 dually reactive and 119 (21.8%) as HIV-1 (kappa=0.79; p<0.001). The two tests gave discordant results for 65 samples (11.9%). CONCLUSIONS: Patients with HIV-2 mono infection are correctly discriminated by the national algorithms used in West African countries. HIV-1&2 dually reactive patients should be systematically investigated, with a standardized algorithm using more accurate tests, before initiating ART as at least 4 out of 10 of them could initiate an effective first line ART for HIV-1 and optimize their second-line treatment options. PMID- 25128909 TI - Incidental papillary thyroid carcinoma: clinical characteristics and prognostic factors among patients with Graves' disease and euthyroid goiter, Cleveland Clinic experience. AB - OBJECTIVE: The prevalence and clinical significance of incidental differentiated thyroid cancer (DTC) in patients with Graves' disease (GD) remain uncertain. Thyroid stimulating antibody (TSI Ab)-titers were thought to be responsible for the potentially increased incidence or aggressiveness of PTC in that setting. The aim of this study was to compare the prevalence of incidental DTC among patients with GD and euthyroid goiter (EG), to assess the ability of TSI to predict DTC in GD and to investigate the clinical features that may predict incidental DTC in GD and EG. METHODS: Two hundred and forty eight patients with EG and 245 patients with GD patients who had undergone total thyroidectomy at our institution between 2005 and 2013 were retrospectively selected from our data base. An analysis of incidentally discovered DTC was conducted comparing GD group with EG group. RESULTS: Incidental micro-papillary thyroid cancer (MPTC) was found in 28% in EG group, as compared to 26% in GD group. PTC Patients with GD were significantly younger (44 vs 59) and less likely to have compressive symptoms than with EG before surgery (p<0.001). In GD group, patients with MPTC were also significantly older (p=0.009) than those without, were more likely to have symptomatic goiter (p<0.001), and to have a nodular disease (p<0.001). TSI ab titer did not predict MPTC in GD group (The AUC curve was 0.55 (95% CI: 0.46, 0.64). Among patients with GD and incidental MPTC, 58% of patients had at least one nodule. CONCLUSION: The prevalence of incidental DTC in GD is comparable to EG. Each is increased compared to general population. Age of presentation of PTC was significantly lower in GD suggesting an increased risk for MPTC in GD. Nodule size greater than 1cm predicted incidental DTC whereas TSI ab titers and disease duration did not. PMID- 25128910 TI - Elective single versus double embryo transfer: live birth outcome and patient acceptance in a prospective randomised trial. AB - The purpose of this study was to determine which strategy of embryo transfer has a better trade-off in live birth delivery rate versus multiple pregnancy considering patient acceptance: elective single embryo transfer (eSET) or elective double embryo transfer (eDET). In all, 199 women <38 years of age undergoing their first IVF treatment in a private centre were included in a prospective open-label randomised controlled trial. Patients were randomised into four groups: (1) eSET on Day 3; (2) eSET on Day 5; (3) eDET on Day 3; and (4) eDET on Day 5. Per patient, main analysis included acceptance of assigned group, as well as multiple and live birth delivery rates of the fresh cycle. Secondary analysis included the rates of subsequent cryotransfers and the theoretical cumulative success rate. Of 98 patients selected for eSET, 40% refused and preferred eDET. The live birth delivery rate after eDET was significantly higher after eDET versus eSET (65% vs 42%, respectively; odds ratio=1.6, 95% confidence interval 1.1-2.1). No multiple births were observed after eSET, compared with 35% after eDET. Although live birth delivery is higher with eDET, the increased risk of multiple births is avoided with eSET. Nearly half the patients refused eSET even after having been well informed about its benefits. PMID- 25128911 TI - Preparing for human papillomavirus vaccine introduction in Kenya: implications from focus-group and interview discussions with caregivers and opinion leaders in Western Kenya. AB - BACKGROUND: Cervical cancer claims the lives of 275,000 women each year; most of these deaths occur in low-or middle-income countries. In Kenya, cervical cancer is the leading cause of cancer-related mortality among women of reproductive age. Kenya's Ministry of Public Health and Sanitation has developed a comprehensive strategy to prevent cervical cancer, which includes plans for vaccinating preteen girls against human papillomavirus (HPV) by 2015. To identify HPV vaccine communication and mobilization needs, this research sought to understand HPV vaccine-related perceptions and concerns of male and female caregivers and community leaders in four rural communities of western Kenya. METHODS: We conducted five focus groups with caregivers (n = 56) and 12 key-informant interviews with opinion leaders to explore cervical cancer-related knowledge, attitudes and beliefs, as well as acceptability of HPV vaccination for 9-12 year old girls. Four researchers independently reviewed the data and developed codes based on questions in interview guides and topics that emerged organically, before comparing and reconciling results through a group consensus process. RESULTS: Cervical cancer was not commonly recognized, though it was understood generally in terms of its symptoms. By association with cancer and genital/reproductive organs, cervical cancer was feared and stigmatized. Overall acceptability of a vaccine that prevents cervical cancer was high, so long as it was endorsed by trusted agencies and communities were sensitized first. Some concerns emerged related to vaccine safety (e.g., impact on fertility), program intent, and health equity. CONCLUSION: For successful vaccine introduction in Kenya, there is a need for communication and mobilization efforts to raise cervical cancer awareness; prompt demand for vaccination; address health equity concerns and stigma; and minimize potential resistance. Visible endorsement by government leaders and community influencers can provide reassurance of the vaccine's safety, efficacy and benefits for girls and communities. Involvement of community leadership, parents and champions may also be critical for combatting stigma and making cervical cancer relevant to Kenyan communities. These findings underscore the need for adequate planning and resources for information, education and communication prior to vaccine introduction. Specific recommendations for communication and social-marketing strategies are made. PMID- 25128912 TI - Neurolysis for failed tarsal tunnel surgery. AB - The purpose of the present study was to investigate the causes of failure after tarsal tunnel release and the operative findings in the secondary interventions and the outcomes. The data from 8 patients who had undergone revision surgery for failed tarsal tunnel release at least 12 months earlier were evaluated retrospectively. Only the patients with idiopathic tarsal tunnel syndrome were included, and all had unilateral symptoms. Neurophysiologic tests confirmed the clinical diagnosis of failed tarsal tunnel release in all patients. Magnetic resonance imaging revealed varicose veins within the tarsal tunnel in 1 patient (12.5%) and tenosynovitis in another (12.5%). Open tarsal tunnel release was performed in all patients, and the tibialis posterior nerve, medial and lateral plantar nerves (including the first branch of the lateral plantar nerve), and medial calcaneal nerve were released in their respective tunnels, and the septum between the tunnels was resected. The outcomes were assessed according to subjective patient satisfaction as excellent, good, fair, or poor. During revision surgery, insufficient release of the tarsal tunnel, especially distally, was observed in all the patients, and fibrosis of the tibialis posterior nerve was present in 1 (12.5%). The outcomes according to subjective patient satisfaction were excellent in 5 (62.5%), good in 2 (25%), and fair in 1 (12.5%). The fair outcome was obtained in the patient with fibrosis of the nerve. Insufficient release of the tarsal tunnel was the main cause of failed tarsal tunnel release. Releasing the 4 distinct tunnels and permitting immediate mobilization provided satisfactory results in patients with failed tarsal tunnel release. PMID- 25128913 TI - A minimally invasive "overwrapping" technique for repairing neglected ruptures of the Achilles tendon. AB - About 10% to 25% of acute ruptures of the Achilles tendon go undiagnosed for some time beyond what would be optimal for repair and a return to optimal function. Managing these chronic or neglected ruptures is a surgical challenge, because the tendon ends retract and atrophy and could develop a short, fibrous distal stump. In the present report, a patient with a ruptured right Achilles tendon, neglected for approximately 10 years, is described. The chronically injured tendon was successfully treated by overwrapping the interposed scar at the rupture site. This minimally invasive technique restored tension to the tendon, a prerequisite for which was the presence of functional triceps surae, confirmed by identification of gross contraction of the muscle during tiptoeing. The procedure is contraindicated when the scar tissue is not intact and does not have sufficient laxity to allow adequate dorsiflexion of the ankle after overwrapping the tendon or when the triceps surae are nonfunctional. PMID- 25128914 TI - Use of a flexible implant and bioabsorbable anchor for deltoid rupture repair in bimalleolar equivalent Weber B ankle fractures. AB - Supination external rotation ankle fractures are the most common ankle fracture subtype. Deltoid ligament injuries have often been associated with this type of injury pattern. A missed injury can lead to post-traumatic arthritis and persistent pain. The current data do not support acute deltoid rupture repair. This has been based primarily on level III and IV studies in which less than satisfactory results were reported. We believe that acute deltoid rupture repair could be indicated in select cases. We have outlined a new deltoid repair technique for use with bimalleolar, equivalent supination external rotation ankle fractures using a flexible implant and bioabsorbable anchor. PMID- 25128915 TI - Multiple locations of nerve compression: an unusual cause of persistent lower limb paresthesia. AB - A paucity of appreciation exists that the "double crush" phenomenon can account for persistent leg symptoms even after spinal neural decompression surgery. We present an unusual case of multiple locations of nerve compression causing persistent lower limb paresthesia in a 40-year old male patient. The patient's lower limb paresthesia was persistent after an initial spinal surgery to treat spinal lateral recess stenosis thought to be responsible for the symptoms. It was later discovered that he had peroneal muscle herniations that had caused superficial peroneal nerve entrapments at 2 separate locations. The patient obtained much symptomatic relief after decompression of the peripheral nerve. The "double crush" phenomenon and multiple levels of nerve compression should be considered when evaluating lower limb neurogenic symptoms, especially after spinal nerve root surgery. PMID- 25128916 TI - Evaluation of cold ischemia for preservation of testicular function during partial orchiectomy in the rat model. AB - OBJECTIVE: We hypothesized that cold ischemia during partial orchiectomy would lead to higher serum testosterone levels and preservation of testicular architecture than warm ischemia in a prepubescent rat model. MATERIALS AND METHODS: Eighteen prepubescent male Sprague-Dawley rats were randomized to three different surgical groups: sham surgery, bilateral partial orchiectomy with 30 min of cord compression with cold ischemia, or bilateral partial orchiectomy with 30 min of cord compression with warm ischemia. Animals were killed at puberty, and serum, sperm, and testicles were collected. Histological tissue injury was graded by standardized methodology. RESULTS: Mean serum testosterone levels were 1445 +/- 590 pg/mL for the sham group, 449 +/- 268 pg/mL for the cold ischemia group and 879 +/- 631 pg/mL for the warm ischemia group (p = 0.12). Mean sperm counts were 2.1 * 10(7) for sham, 4.4 * 10(6) for cold ischemia, and 9.9 * 10(6) for the warm ischemia groups (p = 0.48). Histological evaluation revealed significant difference in tissue injury grading with more injury in the cold ischemia than in the warm ischemia group (p = 0.01). CONCLUSIONS: In our preclinical rat model, we found no benefit for cold ischemia over warm ischemia at 30 min. PMID- 25128917 TI - Conversion of calcium sulphide to calcium carbonate during the process of recovery of elemental sulphur from gypsum waste. AB - The production of elemental sulphur and calcium carbonate (CaCO3) from gypsum waste can be achieved by thermally reducing the waste into calcium sulphide (CaS), which is then subjected to a direct aqueous carbonation step for the generation of hydrogen sulphide (H2S) and CaCO3. H2S can subsequently be converted to elemental sulphur via the commercially available chemical catalytic Claus process. This study investigated the carbonation of CaS by examining both the solution chemistry of the process and the properties of the formed carbonated product. CaS was successfully converted into CaCO3; however, the reaction yielded low-grade carbonate products (i.e. <90 mass% as CaCO3) which comprised a mixture of two CaCO3 polymorphs (calcite and vaterite), as well as trace minerals originating from the starting material. These products could replace the Sappi Enstra CaCO3 (69 mass% CaCO3), a by-product from the paper industry which is used in many full-scale AMD neutralisation plants but is becoming insufficient. The insight gained is now also being used to develop and optimize an indirect aqueous CaS carbonation process for the production of high-grade CaCO3 (i.e. >99 mass% as CaCO3) or precipitated calcium carbonate (PCC). PMID- 25128918 TI - Heavy metal and nutrient changes during vermicomposting animal manure spiked with mushroom residues. AB - A pilot-scale trial of four months was conducted to investigate the responses of heavy metal and nutrient to composting animal manure spiked with mushroom residues with and without earthworms. Results showed that earthworm activities accelerated organic matter mineralization (e.g. reduction in C/N ratio, increase in total concentrations of N, P, K) and humification (e.g. increase in humic acid concentration, humification ratio and humification index). Despite composting increased total heavy metal (i.e. As, Pb, Cu, Zn) concentrations irrespective of earthworm, the availability of heavy metals extracted by DTPA significantly (P<0.05) decreased particularly in treatments with earthworms introduced. The shift from available to unavailable fractions of heavy metals was either due to earthworm bioaccumulation, as indicated by total heavy metal concentrations being higher in earthworm tissues, or due to the formation of stable metal-humus complexes as indicated by the promotion of humification. Our results suggest that vermicomposting process could magnify the nutrient quality but relieve the heavy metals risk of agricultural organic wastes. PMID- 25128920 TI - A lower content of de-methylesterified homogalacturonan improves enzymatic cell separation and isolation of mesophyll protoplasts in Arabidopsis. AB - Cell adhesion occurs primarily at the level of middle lamella which is mainly composed by pectin polysaccharides. These can be degraded by cell wall degrading enzymes (CWDEs) during developmental processes to allow a controlled separation of plant cells. Extensive cell wall degradation by CWDEs with consequent cell separation is performed when protoplasts are isolated from plant tissues by using mixtures of CWDEs. We have evaluated whether modification of pectin affects cell separation and protoplast isolation. Arabidopsis plants overexpressing the pectin methylesterase inhibitors AtPMEI-1 or AtPMEI-2, and Arabidopsis pme3 plants, mutated in the gene encoding pectin methylesterase 3, showed an increased efficiency of isolation of viable mesophyll protoplasts as compared with Wild Type Columbia-0 plants. The release of protoplasts was correlated with the reduced level of long stretches of de-methylesterified homogalacturonan (HGA) present in these plants. Response to elicitation, cell wall regeneration and efficiency of transfection in protoplasts from transgenic plants was comparable to those of wild type protoplasts. PMID- 25128921 TI - Identifying primary Sjogren syndrome in children: case report. AB - Primary Sjogren syndrome (PSS) rarely occurs in children. In addition, because the objective and subjective diagnostic criteria for juvenile PSS differ from those seen in adults, identification of its presence can be difficult to establish. This case report illustrates the accepted benchmarks for diagnosing pediatric PSS. PMID- 25128919 TI - Determinants of methicillin-susceptible Staphylococcus aureus native bone and joint infection treatment failure: a retrospective cohort study. AB - BACKGROUND: Although methicillin-susceptible Staphylococcus aureus (MSSA) native bone and joint infection (BJI) constitutes the more frequent clinical entity of BJI, prognostic studies mostly focused on methicillin-resistant S. aureus prosthetic joint infection. We aimed to assess the determinants of native MSSA BJI outcomes. METHODS: Retrospective cohort study (2001-2011) of patients admitted in a reference hospital centre for native MSSA BJI. Treatment failure determinants were assessed using Kaplan-Meier curves and binary logistic regression. RESULTS: Sixty-six patients (42 males [63.6%]; median age 61.2 years; interquartile range [IQR] 45.9-71.9) presented an acute (n = 38; 57.6%) or chronic (n = 28; 42.4%) native MSSA arthritis (n = 15; 22.7%), osteomyelitis (n = 19; 28.8%) or spondylodiscitis (n = 32; 48.5%), considered as "difficult-to treat" in 61 cases (92.4%). All received a prolonged (27.1 weeks; IQR, 16.9-36.1) combined antimicrobial therapy, after surgical management in 37 cases (56.1%). Sixteen treatment failures (24.2%) were observed during a median follow-up period of 63.3 weeks (IQR, 44.7-103.1), including 13 persisting infections, 1 relapse after treatment disruption, and 2 super-infections. Independent determinants of treatment failure were the existence of a sinus tract (odds ratio [OR], 5.300; 95% confidence interval [CI], 1.166-24.103) and a prolonged delay to infectious disease specialist referral (OR, 1.134; 95% CI 1.013-1.271). CONCLUSIONS: The important treatment failure rate pinpointed the difficulty of cure encountered in complicated native MSSA BJI. An early infectious disease specialist referral is essential, especially in debilitated patients or in presence of sinus tract. PMID- 25128922 TI - Does alveolar corticotomy accelerate orthodontic tooth movement when retracting upper canines? A split-mouth design randomized controlled trial. AB - PURPOSE: To evaluate the efficacy of alveolar corticotomy on orthodontic tooth movement when retracting upper canines compared with the conventional technique and to evaluate patients' pain and discomfort levels after corticotomy. MATERIALS AND METHODS: A split-mouth design randomized controlled trial at the Department of Orthodontics (University Al-Baath Dental School) was performed. A total of 30 patients whose orthodontic treatment required canine retraction were included. The predictor variable was the use of corticotomy to facilitate tooth movement. The velocity of space closure was evaluated as the primary outcome variable by measuring the distance between the canine and first molar on each side of the mouth immediately after corticotomy and at 1, 2, 4, 8, and 12 weeks after corticotomy. The levels of pain and discomfort were evaluated as the secondary outcome variables using a questionnaire administered 4 times during the first week after corticotomy. Paired t tests or Wilcoxon matched-pairs signed-rank tests were used to detect significant differences. RESULTS: A total of 30 patients (15 males and 15 females) were recruited with a mean age of 20.04 +/- 3.63 years (range 15 to 24). The space closure velocity after corticotomy was significantly faster on the experimental side than on the control side (mean = 0.74 mm/week vs 0.20 mm/week between 1 week after and immediately after corticotomy, respectively; P < .001). The pain encountered during eating was high, with 50% and 30% of patients reporting severe pain at 1 and 3 days postoperatively, respectively. No significant differences were detected between the male and female patients regarding the tooth movement velocity on the experimental side. CONCLUSIONS: Alveolar corticotomy increased orthodontic tooth movement and was accompanied by moderate degrees of pain and discomfort. PMID- 25128923 TI - Sleeve gastrectomy and mesenteric venous thrombosis: report of 3 patients and review of the literature. PMID- 25128924 TI - Bipolar impedance-controlled sealing of the pulmonary artery with SealSafe G3 electric current: determination of bursting pressures in an ex vivo model. AB - BACKGROUND: In every anatomic lung resection operation, the pulmonary artery itself or its branches must be sealed. This involves either stapling or ligating the vessels. Based on the positive results with the bipolar vessel sealing <=7 mm in abdominal surgery the present study aimed to evaluate burst pressures of the pulmonary artery after sealing with the sealing instrument SealSafe G3 (Gebruder Martin & CoKG, Tuttlingen, Germany). MATERIAL AND METHODS: The whole pulmonary artery above the pulmonary valve was exposed up to the periphery of the left lung in freshly removed pig heart-lung blocks. A pressure-measuring cylinder was then implanted in the prepared vessel on the side at the main trunk of the pulmonary artery to determine the pressure in the vessel. After either ligation or bipolar sealing of the pulmonary artery, the pneumatic burst pressure (millimeters of mercury) was determined in a water bath. Three groups (n = 12 for each seal type) with different vessel diameters were examined: group 1: 0-6 mm, group 2: 7-12 mm, and group 3: >12 mm. In all cases, vessel sealing was performed with a MARSEAL 5 instrument (Gebruder Martin & Co KG, Tuttlingen, Germany) and the SealSafe G3 current. The mean burst pressures of the individual groups (ligature and bipolar sealing) were compared using two-tailed, nonparametric Mann-Whitney U test. Significance was defined as P < 0.05. RESULTS: The mean burst pressures in group 1 were measured by 340 +/- 13.4 mm Hg with ligature and 205 +/- 44.4 mm Hg with bipolar sealing (P < 0.001). In group 2, the mean values obtained were 270 +/- 28.2 mm Hg for ligature and 162 +/- 36.0 mm Hg for bipolar sealing (P < 0.001). In group 3, the mean burst pressures for bipolar sealing were only 52.1 +/- 15.1 mm Hg, whereas those for ligated vessels were 253 +/- 46.9 mm Hg (P < 0.001). For this size of vessel the burst pressure was also determined after stapling. The mean value in this case was 230 +/- 21.8 mm Hg. CONCLUSIONS: In all groups, the mean burst pressures after bipolar sealing were significantly lower than those achieved with ligation, but they were sufficient for a save closure of the pulmonary artery with diameters up to 12 mm. PMID- 25128925 TI - Impact of occult hepatitis B virus infection on outcome after resection for non-B non-C hepatocellular carcinoma. AB - BACKGROUND: To investigate the clinicopathologic characteristics of patients with both hepatitis B virus-surface antigen and hepatitis C virus antibody negative hepatocellular carcinoma (non-B non-C HCC [NBNC-HCC]) and examine the impact of occult hepatitis B virus infection (OBI) on patients' survival. METHODS: All patients with OBI were identified from a database of patients with NBNC-HCC who underwent surgical resection between January 1, 2006, and December 31, 2008. Their clinicopathologic and survival characteristics were compared with NBNC-HCC patients without OBI. RESULTS: Out of the 86 NBNC-HCC patients, 59 patients (68.6%) with OBI. A higher prevalence of hepatitis B core antigen positive rate, low platelet count, portal hypertension, and liver cirrhosis were observed in NBNC-HCC patients with OBI. The 1- and 3-y recurrence free survival rates were 66% and 25% in OBI group and 89% and 70% in the no OBI group, respectively (P < 0.001). The 1-, 3-, and 5-y overall survival rates were 86%, 55%, and 51% in OBI group and 93%, 85%, and 66% in no OBI group, respectively (P = 0.112). Multivariate analysis revealed that OBI (hazard ratio [HR] = 2.122; 95% confidence interval [CI], 1.086-4.149; P = 0.028), liver cirrhosis (HR = 2.411; 95% CI, 1.337-4.345; P = 0.003), and vascular invasion (HR = 5.858; 95% CI, 2.799 12.261; P < 0.001) were independent poor prognostic factors for recurrence free survival of patients with NBNC-HCC. CONCLUSIONS: NBNC-HCC patients with OBI had a poorer prognosis. OBI can be a useful predictor for recurrence in patients with NBNC-HCC after surgery. PMID- 25128926 TI - Comparative metabolic flux analysis of an Ashbya gossypii wild type strain and a high riboflavin-producing mutant strain. AB - In the present study, we analyzed the central metabolic pathway of an Ashbya gossypii wild type strain and a riboflavin over-producing mutant strain developed in a previous study in order to characterize the riboflavin over-production pathway. (13)C-Metabolic flux analysis ((13)C-MFA) was carried out in both strains, and the resulting data were fit to a steady-state flux isotopomer model using OpenFLUX. Flux to pentose-5-phosphate (P5P) via the pentose phosphate pathway (PPP) was 9% higher in the mutant strain compared to the wild type strain. The flux from purine synthesis to riboflavin in the mutant strain was 1.6%, while that of the wild type strain was only 0.1%, a 16-fold difference. In addition, the flux from the cytoplasmic pyruvate pool to the extracellular metabolites, pyruvate, lactate, and alanine, was 2-fold higher in the mutant strain compared to the wild type strain. This result demonstrates that increased guanosine triphosphate (GTP) flux through the PPP and purine synthesis pathway (PSP) increased riboflavin production in the mutant strain. The present study provides the first insight into metabolic flux through the central carbon pathway in A. gossypii and sets the foundation for development of a quantitative and functional model of the A. gossypii metabolic network. PMID- 25128927 TI - Role of vitamin C and selenium in attenuation of nicotine induced oxidative stress, P53 and Bcl2 expression in adult rat spleen. AB - Forty adult female rats were randomly divided into four groups: control, nicotine, nicotine+vitamin C and nicotine+selenium group. Splenic tissues concentrations of thiobarbituric acid reactive substances (TBARS), nitric oxide, superoxide dismutase (SOD) and catalase (CAT) activities were measured. The P53 and Bcl2 proteins were detected by Western blot and their expression in splenic tissues were measured by quantitative real time PCR in all groups. Compared to control group, nicotine increased the concentrations of TBARS and nitric oxide significantly. However, Vit. C or Se supplementation with nicotine caused a significant decrease in these concentrations. SOD and CAT activities of nicotine group decreased significantly compared to control group. Treatment with Vit. C or Se plays a significant role in elevation of SOD and CAT activities. In splenic tissues, nicotine significantly decreases the protein levels and the mRNA expression of P53 and increases the protein levels of Bcl2 and its expression. Administration of Vit. C. to nicotine-treated rats completely reversed the decrease in P53 levels and its mRNA expression and the increase in Bcl2 levels and its mRNA expression to the control values. In contrast, Se administration did not induce any significant changes in these genes levels or expressions compared to nicotine group. CONCLUSION: Vit. C supplementation to nicotine treated rats was more effective than selenium in attenuation of nicotine-induced oxidative stress, p53 and Bcl2 expression in rat spleen tissues. PMID- 25128928 TI - A systematic review of the effect of daily panty liner use on the vulvovaginal environment. AB - BACKGROUND: Whether panty liners predispose to vulvovaginitis is unclear. OBJECTIVES: To clarify the effects of the use of panty liners on the female genital tract. SEARCH STRATEGY: Several electronic databases (including PubMed and Embase) were searched to identify studies published in English before May 3, 2012. SELECTION CRITERIA: Case-control studies, randomized controlled trials, and cohort studies comparing young women who did and did not use panty liners in the intermenstrual period were included. DATA COLLECTION AND ANALYSIS: The quality of the studies was assessed using the Newcastle-Ottawa Scale or the Jadad Scale. Data from suitable studies were extracted for analysis. MAIN RESULTS: Five articles met the inclusion criteria. Four studies-all of which included only healthy women-found no significant clinical implications arising from the use of panty liners. The fifth study was of women with recurrent candidiasis and showed that use of panty liners was associated with new candidiasis episodes. CONCLUSIONS: The intermenstrual use of panty liners does not seem to have a negative effect on the vulvovaginal area. PMID- 25128929 TI - Pilot community-mobilization program reduces maternal and perinatal mortality and prevents obstetric fistula in Niger. AB - OBJECTIVE: To assess the impact of a pilot community-mobilization program on maternal and perinatal mortality and obstetric fistula in Niger. METHODS: In the program, village volunteers identify and evacuate women with protracted labor, provide education, and collect data on pregnancies, births, and deaths. These data were used to calculate the reduction in maternal mortality, perinatal mortality, and obstetric fistula in the program area from July 2008 to June 2011. RESULTS: The birth-related maternal mortality fell by 73.0% between years 1 and 3 (P<0.001), from 630 (95% confidence interval [CI] 448-861) to 170 (95% CI 85-305) deaths per 100 000 births. Early perinatal mortality fell by 61.5% (P<0.001), from 35 (95% CI 31-40) to 13 (95% CI 10-16) deaths per 1000 births. No deaths due to obstructed labor were reported after the lead-in period (February to June 2008). Seven cases of community-acquired fistula were reported between February 2008 and July 2009; from August 2009 to June 2011 (23 months; 12 254 births), no cases were recorded. CONCLUSION: Community mobilization helped to prevent obstetric fistula and birth-related deaths of women and infants in a large, remote, resource-poor area. PMID- 25128930 TI - Emerging lessons from the FIGO LOGIC initiative on maternal death and near-miss reviews. AB - This short paper describes some early findings from an overview of the maternal death or severe morbidity "near-miss" reviews that have been undertaken to improve clinical care by the eight societies participating in the FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC) Initiative in Maternal and Newborn Health aimed at strengthening the role of professional obstetric associations. While it is expected that each will publish its own report, generalizable lessons emerged and valuable solutions were implemented that will help others planning such reviews and audits in future. PMID- 25128931 TI - Norepinephrine infusion with and without alpha-adrenergic blockade by phentolamine increases salivary alpha amylase in healthy men. AB - BACKGROUND: Mental stress reliably induces increases in salivary alpha amylase (sAA), a suggested surrogate marker for sympathetic nervous system (SNS) reactivity. While stress-induced sAA increases correlate with norepinephrine (NE) secretion, a potential mediating role of noradrenergic mechanisms remains unclear. In this study, we investigated for the first time in humans whether a NE stress-reactivity mimicking NE-infusion with and without alpha-adrenergic blockade by phentolamine would induce changes in sAA. METHODS: In a single-blind placebo-controlled within-subjects design, 21 healthy men (29-66 years) took part in three different experimental trials varying in terms of substance infusion with a 1-min first infusion followed by a 15-min second infusion: saline-infusion (trial-1), NE-infusion (5 MUg/min) without alpha-adrenergic blockade (trial-2), and with phentolamine-induced non-selective blockade of alpha1- and alpha2 adrenergic receptors (trial-3). Saliva samples were collected immediately before, during, and several times after substance infusion in addition to blood pressure and heart rate readings. RESULTS: Experimental trials significantly differed in sAA reactivity to substance-infusion (p=.001) with higher sAA reactivity following NE-infusion with (trial-3; p=.001) and without alpha-adrenergic blockade (trial-2; p=.004) as compared to placebo-infusion (trial-1); sAA infusion reactivity did not differ between trial-2 and trial-3 (p=.29). Effective phentolamine application was verified by blood pressure and heart rate infusion reactivity. Salivary cortisol was not affected by NE, either with or without alpha-adrenergic-blockade. CONCLUSIONS: We found that NE-infusion stimulates sAA secretion, regardless of co-administered non-selective alpha-adrenergic blockade by phentolamine, suggesting that the mechanism underlying stress-induced sAA increases may involve NE. PMID- 25128932 TI - A new Brucella canis species-specific PCR assay for the diagnosis of canine brucellosis. AB - Brucellosis is a zoonotic disease that is transmitted from animals to humans, and the development of a rapid, accurate, and widely available identification method is essential for diagnosing this disease. In this study, we developed a new Brucella canis species-specific (BcSS) PCR assay and evaluated its specificity and sensitivity. A specific PCR primer set was designed based on the BCAN_B0548 0549 region in chromosome II of B. canis. The PCR detection for B. canis included amplification of a 300-bp product that is, not found on other Brucella species or, genetically or serologically related bacteria. The detection limit of BcSS PCR assay was 6pg/MUl by DNA dilution, or 3*10(3) colony-forming units (CFU) in the buffy coats separated from whole blood experimentally inoculated with B. canis. Using the buffy coat in this PCR assay resulted in approximately 100-times higher sensitivity for B. canis as compared to detect directly from whole blood. This is the first report of a species-specific PCR assay to detect B. canis, and the new assay will provide a valuable tool for the diagnosis of B. canis infection. PMID- 25128933 TI - Repair of a radial tear in the posterior horn of the lateral meniscus. AB - BACKGROUND: There have been no studies evaluating the clinical results after repair of a radial tear in the posterior horn of the lateral meniscus (PHLM) using the FasT-Fix system. This study was undertaken to evaluate the clinical outcomes after repair of a radial tear in the PHLM using the FasT-Fix system in conjunction with anterior cruciate ligament (ACL) reconstruction. METHODS: Between September 2008 and August 2011, 15 radial tears in the PHLM identified during 132 consecutive ACL reconstructions were repaired using the FasT-Fix meniscal repair system. We classified the radial tears into three types according to the tear patterns: simple radial tear, complex radial tear, and radial tear involving the popliteal hiatus. Postoperative evaluation was performed using the Lysholm knee score and Tegner activity level. Second-look arthroscopy was performed in all cases. RESULTS: The mean follow-up period was 24 months. None of the patients had a history of recurrent effusion, joint line tenderness or a positive McMurray test. The meniscal repair was considered to have a 100% clinical success rate. At the final follow-up, the Lysholm knee score and Tegner activity level were significantly improved compared to the preoperative values. On the second-look arthroscopy, repair of radial tears in the PHLM in conjunction with ACL reconstruction using the FasT-Fix device resulted in complete or partial healing in 86.6% of cases. CONCLUSION: Clinical results after meniscal repair of a radial tear in the PHLM by using the FasT-Fix system were satisfactory. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 25128935 TI - Renal denervation in hypertension: simplicity, or complexity? PMID- 25128934 TI - Management of outpatients in France with stable coronary artery disease. Findings from the prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY) registry. AB - BACKGROUND: Improvements in the treatment of coronary artery disease mean that an increasing number of patients survive acute cardiovascular events and live as outpatients with or without anginal symptoms. AIM: To determine the characteristics and management of contemporary outpatients with stable coronary artery disease in Western Europe, and to compare France with the other Western European countries. METHODS: CLARIFY (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an international, prospective, observational, longitudinal study. Between November 2009 and July 2010, 32,954 adult outpatients with stable coronary artery disease (defined as a history of documented myocardial infarction [of >3 months], prior coronary revascularization, chest pain with myocardial ischaemia, or coronary stenosis of>50% proven by angiography) were enrolled in 45 countries. The demographics and management of CLARIFY patients enrolled in France were compared with those enrolled in other Western European countries (Austria, Belgium, Denmark, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland and the UK). RESULTS: Of the 14,726 patients enrolled in Western Europe (mean age 66.2 [10.2] years; 79.6% male), 2432 (16.5%) were from France. The use of aspirin was lower in France than in other Western European countries (74.5% vs. 86.9%, respectively), whereas use of thienopyridines (48.5% vs. 21.7%), oral anticoagulants (12.3% vs. 9.0%) and lipid-lowering drugs (95.8% vs. 92.5%) was higher. Beta-blockers were used in 73% of both groups. Angina was less prevalent in France (6.3% vs. 15.5%) and French patients showed higher levels of physical activity than their counterparts in Western Europe. CONCLUSIONS: The management of patients with stable CAD in France appears favourable, with good adherence to guideline-based therapies, but there remains room for improvement in terms of symptom and risk factor control. PMID- 25128937 TI - Close to the heart. PMID- 25128938 TI - The promise of high-sensitivity troponin testing. PMID- 25128939 TI - Data needs in child maltreatment response. PMID- 25128940 TI - Ocular biomarkers for neurodegenerative and systemic disease. PMID- 25128942 TI - AIDS, loss and renewal. PMID- 25128943 TI - Problem-based learning in medical education: one of many learning paradigms. PMID- 25128944 TI - Excessive occupational sitting is not a "safe system of work": time for doctors to get chatting with patients. PMID- 25128945 TI - Role of the medical community in detecting and managing child abuse. PMID- 25128946 TI - Removing the interview for medical school selection is associated with gender bias among enrolled students. PMID- 25128947 TI - Removing the interview for medical school selection is associated with gender bias among enrolled students. PMID- 25128949 TI - Cardiopulmonary resuscitation--time for a change in the paradigm? AB - Cardiopulmonary resuscitation (CPR) is the default treatment in hospital unless there is a decision to the contrary and this is documented in the patient record. The outcome of CPR in older chronically ill patients is very poor and discharge home is unlikely. Fewer not-for-resuscitation (NFR) orders are written than there are patients who would not benefit from CPR. NFR orders appear to be a marker of death, rather than the result of informed discussion about end-of-life care. There is a legal and ethical framework for the consideration of the suitability of CPR. Discussions about CPR are challenging, and uncertainty is introduced because of the lack of consensus around futility, the emotionally charged nature of the topic, misconceptions about the success of CPR and the failure to recognise that not offering CPR will allow a peaceful and supported death. Discussion around CPR can be misconstrued as a need for consent. A focus on patient and family involvement may result in an expectation that CPR is an entitlement. As part of evidence-based patient-centred care, CPR should only be offered to those for whom it is beneficial. CPR should no longer be the universal default. We propose an opt-in model, which will drive discussion and evaluation of the efficacy and suitability of CPR for the individual. A CPR discussion should occur on admission for all elderly hospital inpatients. PMID- 25128948 TI - A systematic approach to chronic heart failure care: a consensus statement. AB - The National Heart Foundation of Australia assembled an expert panel to provide guidance on policy and system changes to improve the quality of care for people with chronic heart failure (CHF). The recommendations have the potential to reduce emergency presentations, hospitalisations and premature death among patients with CHF. Best-practice management of CHF involves evidence-based, multidisciplinary, patient-centred care, which leads to better health outcomes. A CHF care model is required to achieve this. Although CHF management programs exist, ensuring access for everyone remains a challenge. This is particularly so for Aboriginal and Torres Strait Islander peoples, those from non-metropolitan areas and lower socioeconomic backgrounds, and culturally and linguistically diverse populations. Lack of data and inadequate identification of people with CHF prevents efficient patient monitoring, limiting information to improve or optimise care. This leads to ineffectiveness in measuring outcomes and evaluating the CHF care provided. Expanding current cardiac registries to include patients with CHF and developing mechanisms to promote data linkage across care transitions are essential. As the prevalence of CHF rises, the demand for multidisciplinary workforce support will increase. Workforce planning should provide access to services outside of large cities, one of the main challenges it is currently facing. To enhance community-based management of CHF, general practitioners should be empowered to lead care. Incentive arrangements should favour provision of care for Aboriginal and Torres Strait Islander peoples, those from lower socioeconomic backgrounds and rural areas, and culturally and linguistically diverse populations. Ongoing research is vital to improving systems of care for people with CHF. Future research activity needs to ensure the translation of valuable knowledge and high-quality evidence into practice. PMID- 25128950 TI - Should general practitioners order troponin tests? AB - Cardiac troponin I and T are the preferred biomarkers for assessing myocardial injury, and the timing of troponin testing is fundamental to its clinical utility. There are arguments for and against the use of troponin testing in the community, and the stance that general practitioners should never order a troponin test can be considered an oversimplification. GPs have a generally sufficient understanding of the test for use in primary care, and have a better understanding of false-negative troponin test results than false-positive results. We suggest that hospitalisation, rather than troponin testing, should be the default option for patients with symptoms suggestive of acute coronary syndrome. A single troponin test is reasonable in primary care to exclude the possibility of acute myocardial infarction in asymptomatic low-risk patients whose symptoms resolved at least 12 hours prior. GPs should factor in the complex logistics of troponin testing in the community before ordering a troponin test: results need to be accurate and timely, and might be obtained at a time of day when it is difficult to contact the doctor or the patient. PMID- 25128951 TI - Impact of high-sensitivity cardiac troponin I assays on patients presenting to an emergency department with suspected acute coronary syndrome. AB - OBJECTIVE: To determine whether introduction of high-sensitivity cardiac troponin I (hscTn-I) assays affected management of patients presenting with suspected acute coronary syndrome (ACS) to the emergency department (ED) of a tertiary referral hospital. DESIGN, PATIENTS AND SETTING: A retrospective analysis of all patients presenting to the Geelong Hospital ED with suspected ACS from 23 April 2010 to 22 April 2013 -2 years before and 1 year after the changeover to hscTn-I assays on 23 April 2012. MAIN OUTCOME MEASURES: Hospital admission rates, time spent in the ED, rates of coronary angiography, rates of percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABGS), rates of discharge with a diagnosis of ACS, and rates of inhospital mortality. RESULTS: 12 360 consecutive patients presented with suspected ACS during the study period; 1897 were admitted to Geelong Hospital in the 2 years before and 944 in the 1 year after the changeover to hscTn-I assays. Comparing the two patient groups, there was no statistically significant difference in all-hospital admission rates (95% CI for the difference, - 3.1% to 0.3%; P = 0.10) or proportion of patients subsequently discharged with a diagnosis of ACS (95% CI for the difference, - 2.3% to 5.4%; P = 0.43). After the changeover, the median time patients spent in the ED was 11.5% shorter (3.85 h v 4.35 h; 95% CI for the difference, - 0.59 to - 0.43; P < 0.001) and the proportion of admitted patients undergoing coronary angiography was higher (53.4% v 45.2%; 95% CI for the difference, 4.3 to 12.0 percentage points; P < 0.001), but there was no statistically significant rise in the proportion of patients who had invasive treatment (PCI and/or CABGS) (95% CI for the difference, - 0.4% to 6.3%; P = 0.08). Inhospital mortality rates from ACS did not change significantly (95% CI for the difference, - 1.5% to 0.8%; P = 0.43). CONCLUSION: The introduction of hscTn-I assays appeared to be associated with more rapid diagnosis, resulting in less time spent in the ED, without a change in hospital admission rates. A higher proportion of patients had coronary angiographies after the changeover, but there was no significant change in rates of invasive treatment or inhospital mortality. PMID- 25128952 TI - Trends in hospital admissions for conditions associated with child maltreatment, Northern Territory, 1999-2010. AB - OBJECTIVE: To use hospital admissions data to investigate trends in maltreatment among Northern Territory Aboriginal and non-Aboriginal children. DESIGN, SETTING AND PARTICIPANTS: A historical cohort study using diagnosis and external cause codes from hospital admissions among children aged 0-17 years. MAIN OUTCOME MEASURES: Annual rates of admission with either a definitive or indicative code for child maltreatment. RESULTS: From 1 January 1999 to 31 December 2010, the average annual rates of hospital admission of NT Aboriginal and non-Aboriginal children with a definitive code of maltreatment were 8.8 (95% CI, 7.4-10.2) and 0.91 (95% CI, 0.59-1.22) per 10 000 children, respectively. There was no evidence for change over time in either population. The corresponding rates of admission with a code indicative of maltreatment were 28.4 (95% CI, 25.8-31.1) and 5.2 (95% CI, 4.4-6.0) per 10 000 children, with average annual increases of 3% (incidence rate ratio [IRR], 1.03; 95% CI, 1.00-1.07) and 4% (IRR, 1.04; 95% CI, 0.96-1.11). Physical abuse was the prominent type of maltreatment-related admission in both populations. There were increases in rates of admission for older Aboriginal children (13-17 years) and older non-Aboriginal boys. Most perpetrators in the assault of younger children were family members, while among older children most were not specified. CONCLUSION: Our study shows the utility of hospital admissions for population surveillance of child maltreatment. The relatively stable rate of maltreatment-related hospital admissions among NT Aboriginal children shown here is in contrast to substantial increases reported from child protection data. The results also highlight the overlap between violence within families and in the wider community, particularly for older children, and lends support for population-level interventions to protect vulnerable children. PMID- 25128954 TI - All that is irregular is not AF! PMID- 25128953 TI - Cardiopulmonary arrest and mortality trends, and their association with rapid response system expansion. AB - OBJECTIVES: To understand the changes in the population incidence of inhospital cardiopulmonary arrest (IHCA) and mortality associated with the introduction of rapid response systems (RRSs). DESIGN, SETTING AND PARTICIPANTS: Population-based study of 9 221 138 hospital admissions in 82 public acute hospitals in New South Wales, using data linked to a death registry, from 1 Jan 2002 to 31 Dec 2009. MAIN OUTCOME MEASURES: Changes in IHCA, IHCA-related mortality, hospital mortality and proportion of IHCA patients surviving to hospital discharge. RESULTS: RRS uptake increased from 32% in 2002 to 74% in 2009. This increase was associated with a 52% decrease in IHCA rate, a 55% decrease in IHCA-related mortality rate, a 23% decrease in hospital mortality rate and a 15% increase in survival to discharge after an IHCA (all P < 0.01). The adjusted absolute reductions in IHCA-related mortality and hospital mortality were 1.49 (95% CI, 1.30-1.68) and 4.05 (95% CI, 3.17-4.76) patients per 1000 admissions, respectively. The decrease in IHCA incidence rate accounted for 95% of the reduction in IHCA-related mortality. In contrast, the increase in IHCA survival accounted for only 5% of the reduction in IHCA-related mortality. CONCLUSIONS: During nearly a decade, as RRSs were progressively introduced, there was a coincidental reduction in IHCA, IHCA-related deaths and hospital mortality and an increased survival to hospital discharge after an IHCA. Reduced IHCA incidence, rather than improved postcardiac arrest survival, was the main contributor to the reduction in IHCA mortality. PMID- 25128955 TI - Health care--the secular Leviathan. PMID- 25128958 TI - Targeting death receptors for TRAIL by agents designed by Mother Nature. AB - Selective killing of cancer cells is one of the major goals of cancer therapy. Although chemotherapeutic agents are being used for cancer treatment, they lack selectivity toward tumor cells. Among the six different death receptors (DRs) identified to date, DR4 and DR5 are selectively expressed on cancer cells. Therefore, unlike chemotherapeutic agents, these receptors can potentially mediate selective killing of tumor cells. In this review we outline various nutraceuticals derived from 'Mother Nature' that can upregulate DRs and thus potentiate apoptosis. These nutraceuticals increase tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL)-induced apoptosis of cancer cells through different mechanisms. First, nutraceuticals have been found to induce DRs through the upregulation of various signaling molecules. Second, nutraceuticals can downregulate tumor cell-survival pathways. Third, nutraceuticals alone have been found to activate cell-death pathways. Although both TRAIL and agonistic antibodies against DR4 and DR5 are in clinical trials, combination with nutraceuticals is likely to boost their anticancer potential. PMID- 25128959 TI - Comprehensive evaluation of PCA-based finite element modelling of the human femur. AB - Computed tomography (CT)-based finite element (FE) reconstructions describe shape and density distribution of bones. Both shape and density distribution, however, can vary a lot between individuals. Shape/density indexation (usually achieved by principal component analysis--PCA) can be used to synthesize realistic models, thus overcoming the shortage of CT-based models, and helping e.g. to study fracture determinants, or steer prostheses design. The aim of this study was to describe a PCA-based statistical modelling algorithm, and test it on a large CT based population of femora, to see if it can accurately describe and reproduce bone shape, density distribution, and biomechanics. To this aim, 115 CT-datasets showing normal femoral anatomy were collected and characterized. Isotopological FE meshes were built. Shape and density indexation procedures were performed on the mesh database. The completeness of the database was evaluated through a convergence study. The accuracy in reconstructing bones not belonging to the indexation database was evaluated through (i) leave-one-out tests (ii) comparison of calculated vs. in-vitro measured strains. Fifty indexation modes for shape and 40 for density were necessary to achieve reconstruction errors below pixel size for shape, and below 10% for density. Similar errors for density, and slightly higher errors for shape were obtained when reconstructing bones not belonging to the database. The in-vitro strain prediction accuracy of the reconstructed FE models was comparable to state-of-the-art studies. In summary, the results indicate that the proposed statistical modelling tools are able to accurately describe a population of femora through finite element models. PMID- 25128957 TI - Respondent driven sampling is an effective method for engaging methamphetamine users in HIV prevention research in South Africa. AB - BACKGROUND: South Africa, in the midst of the world's largest HIV epidemic, has a growing methamphetamine problem. Respondent driven sampling (RDS) is a useful tool for recruiting hard-to-reach populations in HIV prevention research, but its use with methamphetamine smokers in South Africa has not been described. This study examined the effectiveness of RDS as a method for engaging methamphetamine users in a Cape Town township into HIV behavioral research. METHODS: Standard RDS procedures were used to recruit active methamphetamine smokers from a racially diverse peri-urban township in Cape Town. Effectiveness of RDS was determined by examining social network characteristics (network size, homophily, and equilibrium) of recruited participants. RESULTS: Beginning with eight seeds, 345 methamphetamine users were enrolled over 6 months, with a coupon return rate of 67%. The sample included 197 men and 148 women who were racially diverse (73% Coloured, 27% Black African) and had a mean age of 28.8 years (SD=7.2). Social networks were adequate (mean network size >5) and mainly comprised of close social ties. Equilibrium on race was reached after 11 waves of recruitment, and after <=3 waves for all other variables of interest. There was little to moderate preference for either in- or out-group recruiting in all subgroups. CONCLUSIONS: Results suggest that RDS is an effective method for engaging methamphetamine users into HIV prevention research in South Africa. Additionally, RDS may be a useful strategy for seeking high-risk methamphetamine users for HIV testing and linkage to HIV care in this and other low resource settings. PMID- 25128960 TI - Retinal vessel diameter measurements by spectral domain optical coherence tomography. AB - PURPOSE: To describe a spectral domain optical coherence (OCT)-assisted method of measuring retinal vessel diameters. METHODS: All Patients with an OCT circle scan centered at the optic nerve head using a Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) were retrospectively reviewed. Individual retinal vessels were identified on infrared reflectance (IR) images and given unique labels both on IR and spectral domain OCT (SD-OCT). Vessel width and vessel types obtained by IR were documented as ground truth. From OCT, measurements of each vessel, including horizontal vessel contour diameter, vertical vessel contour diameter, horizontal hyperreflective core diameter, and reflectance shadowing width, were assessed. RESULTS: A total of 220 vessels from 13 eyes of 12 patients were labeled, among which, 194 vessels (88 arteries and 65 veins confirmed from IR) larger than 40 microns were included in the study. The mean vessel width obtained from IR was 107.9 +/- 36.1 microns. A mean vertical vessel contour diameter of 119.6 +/- 29.9 microns and a mean horizontal vessel contour diameter of 124.1 +/- 31.1 microns were measured by SD-OCT. Vertical vessel contour diameter did not differ from vessel width in all subgroup analysis. Horizontal vessel contour diameter was not significantly different from vessel width for arteries and had strong or very strong correlation with vessel width for veins. CONCLUSION: In our study, vertical vessel contour diameter measured by current commercially available SD-OCT was consistent with vessel width obtained by IR with good reproducibility. This SD-OCT based method could potentially be used as a standard measurement procedure to evaluate retinal vessel diameters and their changes in ocular and systemic disorders. PMID- 25128961 TI - Results of long-term monitoring of normal-tension glaucoma patients receiving medical therapy: results of an 18-year follow-up. AB - PURPOSE: To conduct a >=15-year follow-up assessment of the visual field (VF) in normal-tension glaucoma (NTG) patients receiving medical therapy and to identify risk factors for VF progression. DESIGN: A retrospective clinical study. METHODS: Medical records of 78 eyes of 78 NTG patients monitored for >=15 years were reviewed. VF progression was defined by a mean deviation (MD) deteriorated twice by 3.00 dB from baseline (MD criterion) and an annual decrease in the MD slope exceeding -0.5 dB/year (MD slope criterion). Logistic regression analysis was employed to identify risk factors for VF progression. RESULTS: The mean follow-up period was 18.3 years. The average intraocular pressure (IOP) before treatment was 15.1 +/-1.9 mmHg and the average treated IOP was 13.5 +/-1.5 mmHg with 2.0 medications. Forty-two eyes (53.8%) showed VF progression using the MD criterion and 15 eyes (19.2%) showed a negative MD slope less than -0.5 dB/year. Disc hemorrhage (DH) was observed in 30 eyes (38.5%). The mean VF progression rate was -0.38 +/-0.30 dB/year in the DH group and -0.24 +/-0.28 dB/year in the non-DH group (P = 0.012). Multiple logistic regression analysis identified DH [relative risk (RR) 4.28; P = 0.028] as a risk factor for VF progression using the MD criterion. DH (RR 8.77; P = 0.007) and IOP fluctuation during follow-up (RR 5.03; P = 0.048) were detected as risk factors using the MD slope criterion. CONCLUSIONS: DH and IOP fluctuation were associated with VF progression in NTG during long-term therapy. PMID- 25128963 TI - Editorial. PMID- 25128962 TI - Measurement of retinal nerve fiber layer and macular ganglion cell-inner plexiform layer with spectral-domain optical coherence tomography in patients with optic nerve head drusen. AB - PURPOSE: To evaluate the effect of optic nerve head drusen (ONHD) on the retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) using Cirrus optical coherence tomography (OCT). METHODS: Fifty-seven eyes of thirty patients with ONHD and thirty-eight eyes of twenty age-matched and sex matched control subjects underwent circumpapillary and macular scanning using Cirrus OCT. The percentages of eyes with abnormal GCIPL and RNFL values according to the Cirrus normative data were analysed and compared. RESULTS: Overall, eyes with ONHD showed abnormally reduced values for average and minimum GCIPL thicknesses in 35 % and 45 % of cases compared to 2 % for both values in control eyes (P < 0.001). Average RNFL thickness comparison between eyes with ONHD and normal eyes revealed abnormal thinning in 33 % vs. 0 %, respectively (p = 0.002). The percentage of abnormal thinning increased with higher grades of ONHD for all the parameters evaluated, so that in grade III drusen, values were abnormally reduced in 80 % of eyes in all three analyses. Regarding buried ONHD, 30 % and 4 % of eyes had an abnormally reduced minimum GCIPL and average RNFL thickness, respectively. Furthermore, 26 % of these eyes had abnormal GCIPL exams with a normal or increased RNFL thickness. CONCLUSIONS: Both RNFL and GCIPL analysis reveal significant thinning in eyes with ONHD directly correlated with drusen severity. In buried ONHD, the abnormality rate was significantly higher with GCIPL compared to RNFL evaluation, suggesting that GCIPL analysis might be an early structural indicator of neuronal loss in the setting of thickened RNFL. PMID- 25128964 TI - Twist 1 regulates the expression of PPARgamma during hormone-induced 3T3-L1 preadipocyte differentiation: a possible role in obesity and associated diseases. AB - BACKGROUND: Twist 1 is highly expressed in adipose tissue and has been associated with obesity and related disorders. However, the molecular function of Twist 1 in adipose tissue is unclear. Twist 1 has been implicated in cell lineage determination and differentiation. Therefore, we investigated both the role of Twist 1 in adipocyte precursor mobilization and the relationship of Twist 1 with other molecular determinants of adipocyte differentiation. METHODS: We examined Twist 1 mRNA and protein expression in subcutaneous adipose tissues from diet induced obese C57/BL6 mice and Wistar rats and in obese patients undergoing liposuction or adipose transplant surgeries. Twist 1 expression was measured on days 0, 2, 4, 8, and 12 of 3T3-L1 differentiation in vitro. The role of Twist 1 in adipogenesis was explored using retroviral interference of Twist 1 expression. Adipokine secretion was evaluated using a RayBio(r) Biotin Label-based Adipokine Array. RESULTS: Twist 1 mRNA and protein levels were reduced in diet-induced obese mice and rats and in obese humans. Twist 1 was upregulated during 3T3-L1 preadipocyte differentiation in vitro, beginning from the fourth day of differentiation induction. Retroviral interference of Twist 1 expression did not significantly impair lipid formation; however, retroviral interference induced PPARgamma mRNA and protein expression on day 4 of differentiation induction. Adipokine array analyses revealed increased secretion of CXCR4 (19.55-fold), VEGFR1 (92.13-fold), L-21 R (63.55-fold), and IL-12 R beta 1 (59.66-fold) and decreased secretion of VEGFR3 (0.01-fold), TSLP R (0.071-fold), MIP-1 gamma (0.069-fold), TNF RI/TNFRSF1A (0.09-fold), and MFG-E8 (0.06-fold). CONCLUSIONS: Twist 1 is a regulator of adipocyte gene expression although it is not likely to regulate differentiation. We identified PPARgamma as a potential target of Twist 1 and found variation in the secretion of multiple adipokines, which might indicate a prospective mechanism linking Twist 1 expression with obesity or associated diseases. PMID- 25128965 TI - Extent of physeal involvement in Legg-Calve-Perthes disease. AB - PURPOSE: The growth plate involvement (GPI) index is reportedly a reliable predictor of final radiographic outcome in Legg-Calve-Perthes disease (LCPD). We determined whether (1) the GPI index was associated with the lateral pillar classification, (2) the GPI index could predict the final radiographic outcome, and (3) the geometry of proximal femur was affected by presence of physeal involvement. METHODS: We reviewed 47 patients with unilateral LCPD who were treated conservatively. The mean duration of follow-up was 9.5 years (range, five to 13 years). The affected hips were categorized into those with and without physeal involvement. Herring classifications were determined and the GPI indices were estimated at the stage of maximum fragmentation. The Stulberg classification, leg length discrepancy (LLD), articulotrochanteric distance (ATD) index, neck-shaft angle (NSA), neck width and height were determined at skeletal maturity. RESULTS: The GPI indices were lower in Herring groups A and B (p < 0.001) and Stulberg classes I and II (p = 0.002), and these values were increased in the Herring group B/C and C and Stulberg classes III, IV and V. However, the age of onset, LLD and ATD index at skeletal maturity were not associated with the GPI index. The NSA of the affected hips with physeal involvement was significantly different compared to that of unaffected hips (p < 0.001). CONCLUSIONS: The GPI index could be used to determine the extent of physeal involvement in LCPD, and might be considered one of the prognostic values of radiographic development in patients with LCPD who are treated conservatively. PMID- 25128966 TI - Primary cementless hip arthroplasty as a potential risk factor for non-union after long-stem revision arthroplasty in periprosthetic femoral fractures. AB - PURPOSE: In case of stem loosening in periprosthetic femoral fractures (PPFF), revision arthroplasty should be performed. The first hypothesis of this study was that advanced patient age and female gender shows higher non-union rates. The second hypothesis was that primary cementless arthroplasty is associated with a higher non-union rate compared to cemented primary hip arthroplasty. METHODS: All PPFF occurring between January 2000 and June 2010 treated by revision arthroplasty were included. Multiple regression analysis was performed to identify independent variables leading to fracture non-union. RESULTS: Eighty one patients (78 % female) met the inclusion criteria. In 20/81 patients (24.7 %) no adequate fracture healing could be determined on radiographs 12 months after revision surgery. Although age and female gender showed a positive correlation with bony non-union after PPFF as expected, the p-values were not statistically significant. Multiple regression analysis revealed primary cementless prosthesis (p = 0.001) to be the only independent variable associated with non-union. CONCLUSION: Non-cemented primary prosthesis might be a negative predicting factor for the development of non-union after long-stem revision arthroplasty in PPFF. We therefore recommend the thorough debridement of pannus tissue thus inducing bone healing before the implantation of revision prostheses. PMID- 25128967 TI - Pre-operative scoring system to determine the surgical strategy for periprosthetic hip infection. AB - PURPOSE: The aim of this study was to evaluate the results of one- and two-stage revision total hip arthroplasties (THAs) and to determine a rational surgical treatment strategy for periprosthetic hip infections. METHODS: We constructed a 12-point preoperative scoring system to suggest either one- or two-stage revision THAs, based on a retrospective analysis of 55 operative procedures. Prosthesis survival was analysed using the Kaplan-Meier method, and the validity of the scoring system was evaluated using receiver-operating characteristic curves. RESULTS: At the end point of implant removal due to recurrent infection, the ten year survival rates were 94 and 87% for one- and two-stage revision THAs, respectively. One-stage revision THA was recommended for patients scoring >9 points. The risk of recurrent infection in patients scoring 4 points was 83%. The sensitivity and specificity of a cut-off value of 4 points, determined by the scoring system, were 83 and 100%, respectively. CONCLUSIONS: The novel pre operative scoring system was useful for the management of periprosthetic hip infections. PMID- 25128968 TI - A comparison of ACL reconstruction using patellar tendon versus hamstring autograft in female patients: a prospective randomised study. AB - PURPOSE: The incidence of an anterior cruciate ligament (ACL) tear is highest in female patients; however, it is not apparent whether graft choice affects clinical results. The aim of this prospective randomised study was to evaluate clinical results of an ACL reconstruction using patellar tendon [bone-patellar tendon-bone (BTB)] or hamstring graft (HS) in female patients. METHODS: Inclusion criteria were traumatic instability, no signs of osteoarthritis, no previous instability and no contralateral knee instability. Inclusion criteria were met in 150 patients, mean age 26 (17-47) years. Patients were randomised into two groups of 75 patients according to graft type; all had the same rehabilitation protocol. Tegner Lysholm knee score and stability were evaluated pre-operatively and one and two years postoperatively. The difference between groups was statistically evaluated using unpaired t test. RESULTS: Of the 150 patients, all completed one year follow-up; three were lost to follow-up at two years. There was no significant difference in functional scores and knee stability between groups. The HS group had significantly less anterior knee pain in the first six months postoperatively. CONCLUSION: ACL reconstruction significantly improves clinical results and stability of the knee. Difference in Lysholm score and stability between groups was not significant. Neither group showed higher tendency to graft failure within two years. Graft choice for reconstruction in female patients should be surgeon specific and individualised, as both grafts studied achieved comparable results. PMID- 25128969 TI - Third-generation minimally invasive correction of hallux valgus: technique and early outcomes. AB - PURPOSE: There is growing evidence supporting minimally invasive surgical (MIS) techniques for correction of symptomatic hallux valgus. The aim of this study was to present a hybrid third-generation technique and assess the safety and efficacy from the first 45 procedures. METHODS: Forty-five consecutive feet underwent a third-generation MIS distal chevron osteotomy with a minimum six month follow-up (range six to 17 months). This technique uses both first- and second-generation techniques plus a distal chevron osteotomy and screw for improved control and stabilisation of the metatarsal head. All patients were clinically assessed using the Manchester-Oxford Foot Questionnaire (MOXFQ). Radiographic measures included hallux valgus angle (HVA), intermetatarsal angle (IMA), first metatarsal length and overall toe length. RESULTS: There were significant improvements in all three domains of the MOXFQ (p <0.001). There was also significant improvement in all radiographic parameters (p < 0.001). Mean HVA decreased from 30.54 degrees to 10.41 degrees , and the mean IMA decreased from 14.55 degrees to 7.11 degrees . Shortening of the first metatarsal had no effect on clinical outcomes. There was a very low rate of complications. CONCLUSION: The short-term results of this third-generation technique show that it is a safe procedure with good clinical outcomes and compares favourably with earlier techniques. PMID- 25128970 TI - Editorial overview: virus-glycan interactions and pathogenesis. PMID- 25128971 TI - The effects of coronary artery calcium screening on behavioral modification, risk perception, and medication adherence among asymptomatic adults: a systematic review. AB - OBJECTIVE: To perform systematic review of the effects of screening for coronary artery calcium (CAC), a subclinical marker of coronary artery disease (CAD), on behavioral or lifestyle modification, risk perception, and medication adherence. METHODS: We searched through CINAHL, PsychInfo, Web of Science, Cochrane Central Register of Control Trials, and PubMed (Medline) for studies on the effects of CAC screening in asymptomatic individuals across three major domains: behavioral modification, risk perception for CAD, and medication adherence. We extracted data from the retrieved studies, assessed and synthesized the information. RESULTS: Of the 15 retrieved studies, three were randomized control trials and 12 were observational studies. CAC score was ascertained either as total score, quartiles, or standardized Agatston's ordinal scale. While all the 15 studies involved issues related to behavioral and medication adherence, four involved risk perception of CAD. Although no standardized approach was used in these studies, CAC screening enhanced medication adherence in 13 of the 15 studies, while the others were mixed. CONCLUSION: CAC screening improved medication adherence and could likely motivated individuals for beneficial behavioral or lifestyle changes to improve CAD. The mixed results suggest the need for further research because screening for subclinical atherosclerosis has significant implications for early detection and prevention of future cardiovascular events by aggressive risk factors modification. PMID- 25128972 TI - Vulnerable plaque: the biomechanics of matter. PMID- 25128973 TI - Distinct phenotypes of cardiac allograft vasculopathy after heart transplantation: a histopathological study. AB - INTRODUCTION: Long-term survival after heart transplantation (HTx) is hampered by cardiac allograft vasculopathy (CAV). Better understanding of the pathophysiological mechanisms of CAV might have considerable consequences for therapeutic approaches in the future. The aim of the present study was to investigate the histological phenotypes of CAV in relation with clinical patient characteristics. METHODS AND RESULTS: Coronary cross-sections from 51 HTx patients were obtained at autopsy. CAV was observed in 42 patients (82%). Three histological CAV phenotypes were identified (H-CAV 1-3). No CAV (H-CAV 0) is as seen in normal coronary arteries; intimal thickening consisting of a layer of longitudinal oriented smooth muscle cells. In H-CAV 1 to 3 a second intimal layer is formed, on top of the longitudinal oriented smooth muscle cell layer, with predominantly mononuclear inflammatory infiltrate in loose connective tissue (H CAV 1), smooth muscle cells in different orientation (H-CAV 2), or a fibrotic intimal lesion (H-CAV 3). H-CAV type was significantly related with time after transplantation, age at transplantation, the amount of atherosclerotic disease and the occurrence of infection. In addition, morphometric analysis revealed that higher H-CAV types have a relatively larger intimal area, that is compensated for by expansive arterial remodeling of the artery. CONCLUSION: CAV in an ongoing process that can be classified into three different phenotypes; inflammatory lesions, lesions rich of smooth muscle cells and fibrotic lesions. Our results suggest that these phenotypes are related to time after transplantation, age at transplantation, the amount of atherosclerotic disease and the occurrence of infection. PMID- 25128975 TI - The use of pneumatic tourniquet in total knee arthroplasty: a meta-analysis. AB - BACKGROUND: Pneumatic tourniquet use in total knee arthroplasty (TKA) is always a controversial issue. The aim of the present study is to assess the effectiveness and safety of its use in patients receiving primary unilateral TKA, and to explore the most safe and effective protocols. MATERIALS AND METHODS: This review was based on cochrane methodology for conducting meta-analysis. Only randomized controlled trials (RCTs) were eligible for this study. The participants were adults who had undergone primary unilateral TKA. The Review Manager Database (RevMan version 5.0, The Cochrane Collaboration 2008) was used to analyze the dates of the selected studies. RESULTS: Thirteen RCTs involving 859 patients were included in this analysis. The use of tourniquet could significantly reduce operation time (mean difference -5.01 min, P = 0.003), intraoperative blood loss (mean difference -201.85 ml, P < 0.00001) and total blood loss volumes (mean difference -125.03 ml, P = 0.61). But postoperative (mean difference 45.99 ml, P = 0.68) were slightly increased in that situation. With respect to surgical complications, a tendency of increasing risk ratio was observed for tourniquet group. CONCLUSIONS: Our results indicate that tourniquet application could reduce surgical time, intraoperative blood loss and total blood loss, but increases postoperative total blood loss. With respect to postoperative complications, DVT and surgical site infection rates are relatively augmented in the tourniquet group. PMID- 25128974 TI - Association of vascular endothelial factors with cardiovascular outcome and mortality in chronic kidney disease patients: a 4-year cohort study. AB - BACKGROUND: Angiogenic cytokines fms-like tyrosine kinase-1(sFlt-1) and placental growth factor (PlGF) are associated with increased risk for cardiovascular disease (CVD) in the general population. In this study we examine the association between these vascular endothelial factors and atherosclerosis, cardiovascular outcome, and mortality in chronic kidney disease (CKD) patients. METHODS: Serum level of PlGF and sFlt-1 were measured in 301 patients with CKD, who were followed for up to 4 years. Primary outcomes were CV events and all-cause mortality. Carotid-intima media thickness (CIMT) was used as marker of atherosclerosis. Kaplan-Meier survival curves and the Cox proportional hazard model were used to assess the association of biomarkers and clinical outcomes. RESULTS: Mean (SD) PlGF and sFlt-1 were 5.45 ng/ml (3.76) and 68.6 (28.0) pg/ml, respectively. During the follow up time, 60 patients (19.9%) experienced CV events and 22 patients (7.3%) died. Compared with low PlGF, patients with PlGF above median level had higher CV events (12.7% vs. 27.2%, p = 0.002) and mortality (2.0% vs. 12.6%, p < 0.001). The associations of PlGF and sFlt-1 with CV events were not statistically significant in the fully adjusted model. Higher PlGF was associated with greater death risk (HR = 5.22, 95% CI: 1.49-18.33, p = 0.01), which was robust to adjustment for sFlt-1 and other risk factors. Elevated sFlt-1 level was also an independent predictor of mortality (HR 3.41, 95% CI: 1.49-9.51, p = 0.019). CONCLUSION: In CKD patients not yet on dialysis, higher serum level of PlGF and sFlt-1 are associated with increased mortality, but not CV events. PMID- 25128976 TI - Multiplexed aberration measurement for deep tissue imaging in vivo. AB - We describe an adaptive optics method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine the sample-induced aberration. Applicable to fluorescent protein-labeled structures of arbitrary complexity, it allowed us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improved structural and functional imaging of fine neuronal processes over a large imaging volume. PMID- 25128978 TI - Pathobiology of Mycoplasma suis. AB - Mycoplasma suis is an uncultivable bacterium lacking a cell wall that attaches to and may invade the red blood cells of pigs. M. suis infections occur worldwide and cause the pig industry serious economic losses due to the disease known as infectious anaemia of pigs or, historically, porcine eperythrozoonosis. Infectious anaemia of pigs is characterised predominantly by acute haemolytic or chronic anaemia, along with non-specific manifestations, such as growth retardation in feeder pigs and poor reproductive performance in sows. The fastidious nature of M. suis, as well as the lack of an in vitro cultivation system, has hampered the understanding of the biology and pathogenicity of this organism. Pathogenetic mechanisms of M. suis include direct destruction of red blood cells by adhesion, invasion, nutrient scavenging, immune-mediated lysis and eryptosis, as well as endothelial targeting. Recently published genome sequences, in combination with proteome analyses, have generated new insights into the pathogenicity of M. suis. The present review combines these data with the knowledge provided by experimental M. suis infections. PMID- 25128977 TI - Accurate de novo and transmitted indel detection in exome-capture data using microassembly. AB - We present an open-source algorithm, Scalpel (http://scalpel.sourceforge.net/), which combines mapping and assembly for sensitive and specific discovery of insertions and deletions (indels) in exome-capture data. A detailed repeat analysis coupled with a self-tuning k-mer strategy allows Scalpel to outperform other state-of-the-art approaches for indel discovery, particularly in regions containing near-perfect repeats. We analyzed 593 families from the Simons Simplex Collection and demonstrated Scalpel's power to detect long (>=30 bp) transmitted events and enrichment for de novo likely gene-disrupting indels in autistic children. PMID- 25128979 TI - Accumulation of artificial radionuclides in agricultural plants in the area used for surface nuclear tests. AB - The paper reports on the study of artificial radionuclide accumulation in agricultural crops grown at the territory with high concentration of radionuclides, and first of all - with high concentration of transuranium elements. As a result of this work, peculiarities of accumulation and distribution of artificial radionuclides in the vegetative and generative organs of the studied plants have been revealed. Basic accumulation factors have been found for (137)Cs, (90)Sr, (239+240)Pu, and (241)Am in agricultural products. Accumulation factor dependence on type of planting was found for the investigated types of plants. It has been found that the vegetative organs accumulate radionuclides most of all. PMID- 25128980 TI - Extracorporeal membrane oxygenation in adults for severe acute respiratory failure. AB - The purpose of this review is to examine the indications of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). This technique of oxygenation has significantly increased worldwide with the H1N1 flu pandemic. The goal of ECMO is to maintain a safe level of oxygenation and controlled respiratory acidosis under protective ventilation. The enthusiasm for ECMO should not obscure the consideration for potential associated complications. Before widespread diffusion of ECMO, new trials should test the efficacy of early initiation or CO2 removal in addition to, or even as an alternative to mechanical ventilation for severe ARDS. PMID- 25128983 TI - China seeks creative ways to combat smog. PMID- 25128981 TI - The molecular symplesiomorphies shared by the stem groups of metazoan evolution: can sites as few as 1% have a significant impact on recognizing the phylogenetic position of myzostomida? AB - Although it is clear that taxon sampling, alignments, gene sampling, tree reconstruction methods and the total length of the sequences used are critical to the reconstruction of evolutionary history, weakly supported or misleading nodes exist in phylogenetic studies with no obvious flaw in those aspects. The phylogenetic studies focusing on the basal part of bilaterian evolution are such a case. During the past decade, Myzostomida has appeared in the basal part of Bilateria in several phylogenetic studies of Metazoa. However, most researchers have entertained only two competing hypotheses about the position of Myzostomida an affinity with Annelida and an affinity with Platyhelminthes. In this study, dozens of symplesiomorphies were discovered by means of ancestral state reconstruction in the complete 18S and 28S rDNAs shared by the stem groups of Metazoa. By contrastive analysis on the datasets with or without such symplesiomorphic sites, we discovered that Myzostomida and other basal groups are basal lineages of Bilateria due to the corresponding symplesiomorphies shared with earlier lineages. As such, symplesiomorphies account for approximately 1-2% of the whole dataset have an essential impact on phylogenetic inference, and this study reminds molecular systematists of the importance of carrying out ancestral state reconstruction at each site in sequence-based phylogenetic studies. In addition, reasons should be explored for the low support of the hypothesis that Myzostomida belongs to Annelida in the results of phylogenomic studies. Future phylogenetic studies concerning Myzostomida should include all of the basal lineages of Bilateria to avoid directly neglecting the stand-alone basal position of Myzostomida as a potential hypothesis. PMID- 25128984 TI - Human melanocytes form a PAX3-expressing melanocyte cluster on Matrigel by the cell migration process. AB - BACKGROUND: The interactions between human epidermal melanocytes and their cellular microenvironment are important in the regulation of human melanocyte functions or in their malignant transformation into melanoma. Although the basement membrane extracellular matrix (BM-ECM) is one of major melanocyte microenvironments, the effects of BM-ECM on the human melanocyte functions are not fully explained at a molecular level. OBJECTIVE: This study was aimed to characterize the molecular and cellular interactions between normal human melanocytes (NHMs) and BM-ECM. METHODS: We investigated cell culture models of normal human melanocytes or melanoma cells on three-dimensional (3D) Matrigel to understand the roles of the basement membrane microenvironment in human melanocyte functions. Melanogenesis and melanobast biomarker expression in both primary human melanocytes and melanoma cells on 3D Matrigel were evaluated. RESULTS: We found that NHMs migrated and formed reversible paired box 3 (PAX3) expressing cell clusters on three-dimensional (3D) Matrigel. The melanogenesis was significantly decreased in the PAX3 expressing cell cluster. The expression profile of PAX3, SOX10, and MITF in the melanocyte cluster on 3D Matrigel was similar to that of melanoblasts. Interestingly, PAX3 and SOX10 showed an inverse expression profile in NHMs, whereas the inverse expression pattern of PAX3 and SOX10 was disrupted in melanoma MNT1 and WM266-4 cells. CONCLUSION: The human melanocyte culture on 3D Matrigel provides an alternative model system to study functions of human melanoblasts. In addition, this system will contribute to the elucidation of PAX3-related tumorigenic mechanisms to understand human melanoma. PMID- 25128985 TI - Development and clinical evaluation of a novel fully automated qualitative PCR assay for the diagnosis of anogenital herpes simplex virus infection. AB - Molecular detection of viral infections has the potential to improve microbial diagnostics, particularly with the emergence of rapid automated systems. We describe the design of the IDbox fully automated cassette-based system for nucleic acid extraction and real-time PCR amplification and perform a clinical evaluation for the diagnosis of genital herpes simplex infections. At optimal cutoff values determined by receiver-operator curves, the IDbox showed sensitivities of 94.9% (95% confidence interval [CI] 84.9-98.7%) and 97.0% (95% CI 88.5-99.5%) and specificities of 96.7% (95% CI 91.2-98.9%) and 97.3% (95% CI 91.9-99.3%) relative to herpes simplex virus culture and PCR, respectively. We discuss relevant design characteristics and approaches used for each step of the analytical process to enhance assay sensitivity and provide accurate results in the presence of potential cross-reactive organisms and interfering substances. PMID- 25128982 TI - A tree of cellular life inferred from a genomic census of molecular functions. AB - Phylogenomics aims to describe evolutionary relatedness between organisms by analyzing genomic data. The common practice is to produce phylogenomic trees from molecular information in the sequence, order, and content of genes in genomes. These phylogenies describe the evolution of life and become valuable tools for taxonomy. The recent availability of structural and functional data for hundreds of genomes now offers the opportunity to study evolution using more deep, conserved, and reliable sets of molecular features. Here, we reconstruct trees of life from the functions of proteins. We start by inferring rooted phylogenomic trees and networks of organisms directly from Gene Ontology annotations. Phylogenies and networks yield novel insights into the emergence and evolution of cellular life. The ancestor of Archaea originated earlier than the ancestors of Bacteria and Eukarya and was thermophilic. In contrast, basal bacterial lineages were non-thermophilic. A close relationship between Plants and Metazoa was also identified that disagrees with the traditional Fungi-Metazoa grouping. While measures of evolutionary reticulation were minimum in Eukarya and maximum in Bacteria, the massive role of horizontal gene transfer in microbes did not materialize in phylogenomic networks. Phylogenies and networks also showed that the best reconstructions were recovered when problematic taxa (i.e., parasitic/symbiotic organisms) and horizontally transferred characters were excluded from analysis. Our results indicate that functionomic data represent a useful addition to the set of molecular characters used for tree reconstruction and that trees of cellular life carry in deep branches considerable predictive power to explain the evolution of living organisms. PMID- 25128987 TI - Resistance to nucleotide analogue inhibitors of hepatitis C virus NS5B: mechanisms and clinical relevance. AB - The high barrier to the development of resistance to nucleotide analogue inhibitors of the hepatitis C virus (HCV) RNA-dependent RNA polymerase is an intriguing property of this class of drugs. The S282T substitution in the viral polymerase confers resistance to 2'-C-methylated nucleotide analogues. Although this mutation can be selected in HCV replicons, it has only been identified in very few cases in the clinic. Alternative resistance pathways are likewise rarely seen in vivo. Possible underlying mechanisms that are associated with the selection and establishment of a resistant genotype are discussed in this review. PMID- 25128989 TI - Misery of mystery of Muzaffarpur. PMID- 25128988 TI - Sodium channel point mutations associated with pyrethroid resistance in Chinese strains of Culex pipiens quinquefasciatus (Diptera: Culicidae). AB - BACKGROUND: Pesticide resistance due to sodium channel point mutations has been well documented in many mosquito species. METHODS: We tested the resistance of six, wild, Chinese populations of the mosquito Culex pipiens quinquefasciatus to deltamethrin and cyhalothrin. The full length of the sodium channel gene was cloned and sequenced from a pooled sample of mosquitoes from each population. RESULTS: Seven amino acid alterations were found (V250M, R436K, M943V, I973T, L1035F, L1035S and E1901D). Correlation between the frequencies of these mutations and the level of pesticide resistance (LC50) associated with them indicates that those at position L1035 (corresponding to position L1014F in the house fly, Musca domestica; GenBank Accession No.: X96668) are associated with resistance to deltamethrin and cyhalothrin. The frequency of the L1035F mutation was significantly correlated with resistance to deltamethrin (R2 = 0.536, P = 0.049) and cyhalothrin (R2 = 0.626, P = 0.030), and the combined frequency of the L1035F and L1035S mutations was significantly correlated with resistance to both deltamethrin (R2 = 0.661, P = 0.025), and cyhalothrin (R2 = 0.803, P = 0.008). None of the other mutations were correlated with either deltamethrin or cyhalothrin resistance. Interestingly, an HWE test indicated significant linkage between the M943V and I973T mutations (P < 0.01), but further research is required to determine the biological significance of this linkage. CONCLUSIONS: Identifying these mutations may be of practical benefit to the development of pesticide resistance management programs. PMID- 25128990 TI - Diagnostic tool for neuromotor impairment for primary care physician. PMID- 25128991 TI - Indigenous diagnostic tool for neuromotor impairments for primary care physician. PMID- 25128992 TI - Predictors of mortality in neonates with meconium aspiration syndrome. PMID- 25128994 TI - Effects of elevated blood lead levels in preschool children in urban Vellore. AB - OBJECTIVE: To study the burden and associated risk factors for elevated blood lead levels among pre-school children (15-24 months) in urban Vellore, and to study its effects on child cognition and anemia. DESIGN: An investigative study through Mal-ED cohort. SETTING: Eight adjacent urban slums in Vellore, Tamil Nadu. PARTICIPANTS: 251 babies recruited through Mal-ED Network. OUTCOME MEASURES: Blood lead levels using Graphite Furnace Atomic Absorption Spectrophotometry method at 15 and 24 mo; hemoglobin estimation by azidemethemoglobin method; cognitive levels using Bayley Scales of Infant Development III. RESULTS: Around 45% of children at 15 months and 46.4% at 24 months had elevated blood lead levels (>10 ug/dL). Among children who had elevated blood lead levels at 15 months, 69.2% (45/65) continued to have elevated levels at 24 months. After adjusting for potential confounders, children from houses having a piped drinking water supply and houses with mud or clay floors were at significantly higher risk of having elevated blood lead levels at 15 months. Thirty one percent (21/67) of the children with elevated blood lead levels had poor cognitive scores. Children with elevated blood lead levels at 15 months had higher risk (Adjusted OR 1.80; 95% CI 0.80 - 3.99) of having poorer cognitive scores at 24 months. More than half of the children (57%) were anemic at 15 months of age, and elevated blood lead levels were not significantly associated with anemia. CONCLUSIONS: Elevated blood lead levels are common among preschool children living in urban slums of Vellore. Poorer conditions of the living environment are associated with elevated lead levels. PMID- 25128993 TI - INCLEN Diagnostic Tool for Neuromotor Impairments (INDT-NMI) for primary care physician: development and validation. AB - OBJECTIVE: To develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro-motor impairment among 2-9 year old children in primary care settings. STUDY DESIGN: Modified Delphi technique involving national (n=49) and international (n=6) experts was used for development of INDT-NMI. The tool was then validated through a cross sectional study. SETTING: Neurology specialty clinics of three tertiary care pediatric centers in New Delhi, India. PARTICIPANTS: 454 children aged 2-9 years [mean (SD) age: 60.4 (23.7) mo], selected through systematic random sampling, underwent assessment for identification and classification of neuromotor impairments (NMI). INTERVENTION: All study subjects were first administered INDT-NMI (candidate test) by a trained physician followed by expert assessment for NMI and other neurodevelopment disorders (NDD) by team of two pediatric neurologists (Gold standard). RESULTS: According to expert evaluation, 171 (37.8%) children had neuromotor impairments. There were four categories of subjects: NMI alone (n=66); NMI+other NDDs (n=105); Other NDDs without NMI (n=225) and 'Normal' group (n=58). Using expert evaluation as gold standard, overall sensitivity of the INDT-NMI was 75.4% and specificity was 86.8%. INDT-NMI helped graduate physicians to correctly classify 86.6% (112/129) children with NMI into different types (cerebral palsy, neuromotor diseases and other NMI). Graduate physicians assigned 40 children (8.8%) as 'indeterminate', 38 (95%) of whom had either NDD and/or NMI and thus merited referral. Misclassification of NMI occurred in those with mild changes in muscle tone, dystonia, or ataxia and associated NDDs. CONCLUSIONS: Graduate primary care physicians with a structured short training can administer the new tool and diagnose NMI in 2-9 year old children with high validity. INDT-NMI requires further evaluation in actual primary care settings. PMID- 25128995 TI - Incorporating developmental screening and surveillance of young children in office practice. AB - CONTEXT: Developmental concerns voiced by parents need to be responded to by structured developmental screening. Screening is the use of validated developmental screening tools to identify children with high risk of developmental delay out of an apparently normal population, while surveillance is the process of monitoring children identified as high risk by screening. Absence of routine screening can be attributed to problems at the level of parents, pediatricians or National policies. Hence vulnerable children are not detected early, and are denied benefit from appropriate developmental interventions. There are no definite guidelines for screening or for suitable tools for screening and surveillance. OBJECTIVES: To review existing developmental screening and monitoring tools for children validated in Indian under-five children, and provide a proposed practice paradigm for developmental screening in office practice. EVIDENCE ACQUISITION: Scientific papers were retrieved by an electronic database search using MeSH terms 'screening tool', 'developmental delay', and filter of 'children under 5 years'. Those relevant to office practice and validated internationally or in Indian children were reviewed. RESULTS: Screening tools applicable to Indian office practice have been compared and certain tools have been recommended according to the level of risk of developmental delay. An algorithmic approach to screening has been given along with strategies for incorporation. CONCLUSIONS: Screening and surveillance for high risk of developmental delay are essential components of child health care. It is possible to incorporate both into routine practice. PMID- 25128996 TI - Predictors of mortality in neonates with meconium aspiration syndrome. AB - OBJECTIVE: To identify risk factors for mortality in neonates with meconium aspiration syndrome. METHODS: All neonates (2004-2010) with meconium aspiration syndrome, irrespective of gestation were included. Risk factors were compared between those who died and survived. RESULTS: Out of 172 included neonates, 44 (26%) died. Mean (SD) gestation and birth weight were 37.9 (2.3) weeks and 2545 (646g), respectively. Myocardial dysfunction [aOR 28.4; 95% CI (8.0-101); P<0.001] and higher initial oxygen requirement [aOR 1.04; 95% CI (1.02-1.07); P<0.001] increased odds of dying while a higher birth weight [aOR 0.998; 95% CI (0.997-1.00); P=0.005] reduced the odds of dying. CONCLUSIONS: Meconium aspiration syndrome is associated with significant mortality. Myocardial dysfunction, birth weight, and initial oxygen requirement are independent predictors of mortality. PMID- 25128997 TI - Multicystic dysplastic kidney: a retrospective study. AB - OBJECTIVE: To report the renal structural and functional anomalies in children with multicystic dysplastic kidneys. METHODS: Retrospective descriptive analysis of 47 children with multicystic dysplastic kidney seen in a pediatric nephrology unit over a period of 6 years. RESULTS: Antenatal diagnosis of multicystic dysplastic kidney was made in 34 (72.3%) patients. On follow up of 31 children for more than 12 months, 21 (68%) had involution, 4 [13%] had non-regression, and 4 (13%) were nephrectomized. Vesico-ureteric reflux (n=13; 28%) was the commonest renal abnormality. The serum creatinine values were higher (P=0.006) in children with contralateral reflux. Sub-nephrotic proteinuria was noted in 9 (29%) and was significantly associated with complete involution (P=<0.023). None of the patients developed hypertension and 2 (6.4%) had renal failure. CONCLUSIONS: Close nephrological follow-up is needed in children with multicystic dysplasia of kidneys. PMID- 25128998 TI - Off-label use of drugs in neonatal intensive care units. AB - OBJECTIVE: To estimate proportion of off-label medication use in neonates and to evaluate evidence of efficacy and safety of these medications. METHODS: Chart audit in neonatal intensive care units of two institutions in Chandigarh, India. RESULTS: Among 568 prescriptions in 156 neonates, 286 (50%) were off-label. Of these, 56% drugs were not approved for use in neonatal age group and 26% prescriptions were off-label for frequency, dose, indication, route or rate. Most common off-label drugs were anti-infective and antiepileptic. Despite lack of regulatory approval, one-third off-label drugs had level I-II evidence of safety and efficacy for use in neonates. CONCLUSION: Use of off-label drugs is common in sick neonates. PMID- 25128999 TI - A mathematical algorithm for detection of late-onset sepsis in very-low birth weight infants: a preliminary diagnostic test evaluation. AB - OBJECTIVE: To study the diagnostic ability of RALIS (computerized mathematical algorithm and continuous monitoring device) to detect late onset sepsis among very low birth weight preterm neonates. METHODS: Randomly chosen 24 very low birth weight infants with proven sepsis were compared to 22 infants without sepsis. The clinical parameters were retrospectively collected from the medical records. The ability of RALIS to detect late onset sepsis was calculated. RESULTS: RALIS positively identified 23 of the 24 infants with sepsis (sensitivity 95.8%). It indicated sepsis alert median 2.0 days earlier than clinical suspicion. A false positive alert was indicated in 23% (5/22) infants. The specificity, and positive and negative predictive ability of RALIS were 77.3%. 82.1% and 94.4%, respectively. CONCLUSION: RALIS may aid in the early diagnosis of late onset sepsis in very low birth weight preterm infants. PMID- 25129000 TI - Clinical profile of scrub typhus in children and its association with hemophagocytic lymphohistiocytosis. AB - OBJECTIVE: To study the clinical profile of children with scrub typhus and its association with hemophagocytic lymphohistiocytosis. METHODS: Children presenting with unexplained fever and multi-systemic involvement between May to December 2011 were tested for scrub typhus using IgM ELISA kits. Occurrence of Hemophagocytic lymphohistiocytosis in IgM positive cases of scrub typhus was studied. RESULTS: Of the 35 children with unexplained fever and multi-systemic involvement, 15 children (9 boys) tested positive for scrub typhus. Thrombocytopenia, hypoalbuminemia and raised hepatic transaminases were observed in all children. Out of seven children evaluated for hemophagocytic lymphohistiocytosis. 3 met the criteria for hemophagocytosis. Two children (one with hemophagocytic lymphohistiocytosis) died. CONCLUSIONS: Scrub typhus is a common cause of unexplained fever in children in northern India. Hemophagocytic lymphohistiocytosis can occasionally complicate scrub typhus in children. PMID- 25129001 TI - Educating fathers to improve breastfeeding rates and paternal-infant attachment. AB - OBJECTIVE: To determine the effect of breastfeeding education provided to fathers on breastfeeding rates and paternal-infant attachment. METHODS: 117 couples with their infants with the inclusion criteria: knowledge of reading, writing and speaking Turkish; living in the Turkish Republic of North Cyprus until their infants were six months old; and infants having no health problems preventing the early initiation of breastfeeding. Participants were divided into 3 groups (2 experimental and 1 control). Breastfeeding education was provided to the mothers (20 min/d) in the first group (n=38) and to the mothers and fathers in the second group (n=39) (20 min/d/parent) until they were discharged from the hospital. This education was supplemented by a training booklet. The parents and their infants were followed until the infants were six months old. Exclusive breastfeeding rates and Paternal-Infant Attachment Scale scores at six months were main outcome measures. RESULTS: Exclusive breastfeeding rates (56.4%, 33.3% and 12.8%; P<0.001) and mean (SD) Paternal-Infant Attachment Scale scores [89.51(7.05), 82.37 (12.80) and 73.38 (18.67); P<0.001] were highest in the group where education was provided to both mother and father. CONCLUSIONS: Providing breastfeeding education to fathers increases exclusive breastfeeding rates and strengthens paternal attachment. PMID- 25129005 TI - An atypical case of parotid gland swelling and arthritis in a child. AB - BACKGROUND: Early onset sarcoidosis is a rarely reported disease in children. CASE CHARACTERISTICS: 21/2-year-old girl with chronic enlargement of bilateral parotid glands and polyarthritis. OBSERVATION: Biopsy of salivary gland revealed non-caseating granuloma. OUTCOME: Polyarthritis and salivary gland swelling resolved completely after starting oral corticosteroids. MESSAGE: Sarcoidosis is an important differential diagnosis in young children with joint and salivary gland involvement. PMID- 25129006 TI - Successful conversion of post-cardiac surgery electric storm in a child. AB - BACKGROUND: The management of ventricular electrical storm can prove to be a challenge for the clinician given its complexity and life threatening consequences. CASE CHARACTERISTICS: 8-year-old boy with repeated life-threatening polymorphic ventricular tachycardia following aortic valve replacement surgery. INTERVENTION: Defibrillated 45 times in addition to multiple antiarrhythmic drugs. OUTCOME: Conversion to stable sinus rhythm with normal neurological outcome. MESSAGE: Electric storm can be controlled by combination of multiple intravenous antiarrhythmic drugs. PMID- 25129007 TI - Mitochondrial DNA depletion syndrome causing liver failure. AB - BACKGROUND: Mitochondrial DNA depletion syndromes are disorders of Mitochondrial DNA maintenance causing varied manifestations, including fulminant liver failure. CASE CHARACTERISTICS: Two infants, presenting with severe fatal hepatopathy. OBSERVATION: Raised serum lactate, positive family history (in first case), and absence of other causes of acute liver failure. OUTCOME: Case 1 with homozygous mutation, c.3286C>T (p.Arg1096Cys) in POLG gene and case 2 with compound heterozygous mutations, novel c.408T>G (p.Tyr136X) and previously reported c.293C>T (p.Pro98Leu), in MPV17 gene. MESSAGE: Mitochondrial DNA depletion syndrome is a rare cause of severe acute liver failure in children. PMID- 25129008 TI - Immune reconstitution inflammatory syndrome in CNS tuberculosis. AB - BACKGROUND: Immune Reconstitution Inflammatory Syndrome (IRIS), an exaggerated inflammatory response with clinical worsening due to immune recovery during treatment, is rare in the immune-competent population. CASE CHARACTERISTICS: A 5 1/2-year old immune-competent girl with CNS tuberculosis without HIV who developed paradoxical IRIS. OUTCOME: Response to supportive care along with Anti tuberculosis treatment. MESSAGE: IRIS can occur in tuberculosis, even in the immuno-competent. PMID- 25129009 TI - Supplementary suckling technique for relactation in infants with severe acute malnutrition. AB - We report on use of supplementary suckling technique in 62 infants [mean (SD) age 2.5 (1.3) mo] with severe acute malnutrition admitted at our Nutritional rehabilitation Center. It was successful in 34 (55.7%) infants. PMID- 25129010 TI - A modified technique for umbilical arterial catheterization. AB - A modified technique for umbilical artery catheterization was assessed in babies in whom conventional method failed or if the cord was dry. Success rate attained with the modified technique was 90% (19/21). This modified technique could provide an easier and faster method for successful umbilical arterial catheterization. PMID- 25129011 TI - Transient bulging fontanelle after measles vaccination. PMID- 25129012 TI - Onychomadesis. PMID- 25129013 TI - Acute hemorrhagic edema of infancy. PMID- 25129014 TI - X-linked ichthyosis. PMID- 25129015 TI - Atrophoderma vermiculatum. PMID- 25129016 TI - Non-bullous congenital ichthyosiform erythroderma. PMID- 25129017 TI - Crusted scabies. PMID- 25129019 TI - An automatic tool to facilitate the statistical group analysis of DTI. AB - BACKGROUND: Users may have difficulty calculating DTI group statistics since they need to master several complex tools that require high user intervention. A tool called DTIStatistics for the automatic and easy calculation of DTI group statistics was developed to reduce analysis times and possible errors. METHODS: The proposed software was designed by using a user-centred methodology in which we performed an iterative usability evaluation with an expert committee. Once the experts' requirements were fulfilled, we performed a validation of the final version of DTIStatistics with target users, comparing the execution time of this tool and the standard pipeline normally used. RESULTS: Target users needed significantly less time to complete the tasks with DTIStatistics, reducing the analysis time from 1383.78 to 57.2s. They were able to complete all the tasks and barely made errors. Moreover, target users were not able to display the analysis results with the standard pipeline, but when using our tool they only needed 34s. Target users found DTIStatistics easy to learn, use and interact with, and they concluded that they could effectively complete the tasks with it. Additionally, we present example results in the study of depression to demonstrate the validity of DTIStatistics for clinical research. CONCLUSIONS: DTIStatistics facilitates and significantly automates the calculation of DTI group statistics by reducing the analysis times, which implies lower costs. DTIStatistics is highly applicable in clinical research, as demonstrated by the fact that it is currently being used at the University Hospital, University of Navarra (Spain). PMID- 25129020 TI - Visualizing in vivo brain neural structures using volume rendered feature spaces. AB - BACKGROUND: Dendrites of cortical neurons are widely spread across several layers of the cortex. Recently developed two-photon microscopy systems are capable of visualizing the morphology of neurons within deeper layers of the brain and generate large amounts of volumetric imaging data from living tissue. METHOD: For visual exploration of the three-dimensional (3D) structure of dendrites and the connectivity among neurons in the brain, we propose a visualization software and interface for 3D images based on a new transfer function design using volume rendered feature spaces. This software enables the visualization of multidimensional descriptors of shape and texture extracted from imaging data to characterize tissue. It also allows the efficient analysis and visualization of large data sets. RESULTS: We apply and demonstrate the software to two-photon microscopy images of a living mouse brain. By applying the developed visualization software and algorithms to two-photon microscope images of the mouse brain, we identified a set of feature values that distinguish characteristic structures such as soma, dendrites and apical dendrites in mouse brain. Also, the visualization interface was compared to conventional 1D/2D transfer function system. CONCLUSIONS: We have developed a visualization tool and interface that can represent 3D feature values as textures and shapes. This visualization system allows the analysis and characterization of the higher dimensional feature values of living tissues at the micron level and will contribute to new discoveries in basic biology and clinical medicine. PMID- 25129021 TI - OvaSpec - A vision-based instrument for assessing concentration and developmental stage of Trichuris suis parasite egg suspensions. AB - BACKGROUND: OvaSpec is a new, fully automated, vision-based instrument for assessing the quantity (concentration) and quality (embryonation percentage) of Trichuris suis parasite eggs in liquid suspension. The eggs constitute the active pharmaceutical ingredient in a medicinal drug for the treatment of immune mediated diseases such as Crohn's disease, ulcerative colitis, and multiple sclerosis. METHODS: This paper describes the development of an automated microscopy technology, including methodological challenges and design decisions of relevance for the future development of comparable vision-based instruments. Morphological properties are used to distinguish eggs from impurities and two features of the egg contents under brightfield and darkfield illumination are used in a statistical classification to distinguish eggs with undifferentiated contents (non-embryonated eggs) from eggs with fully developed larvae inside (embryonated eggs). RESULTS: For assessment of the instrument's performance, six egg suspensions of varying quality were used to generate a dataset of unseen images. Subsequently, annotation of the detected eggs and impurities revealed a high agreement with the manual, image-based assessments for both concentration and embryonation percentage (both error rates <1.0%). Similarly, a strong correlation was demonstrated in a final, blinded comparison with traditional microscopic assessments performed by an experienced laboratory technician. CONCLUSIONS: The present study demonstrates the applicability of computer vision in the production, analysis, and quality control of T. suis eggs used as an active pharmaceutical ingredient for the treatment of autoimmune diseases. PMID- 25129018 TI - A computational pipeline for quantification of mouse myocardial stiffness parameters. AB - The mouse is an important model for theoretical-experimental cardiac research, and biophysically based whole organ models of the mouse heart are now within reach. However, the passive material properties of mouse myocardium have not been much studied. We present an experimental setup and associated computational pipeline to quantify these stiffness properties. A mouse heart was excised and the left ventricle experimentally inflated from 0 to 1.44kPa in eleven steps, and the resulting deformation was estimated by echocardiography and speckle tracking. An in silico counterpart to this experiment was built using finite element methods and data on ventricular tissue microstructure from diffusion tensor MRI. This model assumed a hyperelastic, transversely isotropic material law to describe the force-deformation relationship, and was simulated for many parameter scenarios, covering the relevant range of parameter space. To identify well fitting parameter scenarios, we compared experimental and simulated outcomes across the whole range of pressures, based partly on gross phenotypes (volume, elastic energy, and short- and long-axis diameter), and partly on node positions in the geometrical mesh. This identified a narrow region of experimentally compatible values of the material parameters. Estimation turned out to be more precise when based on changes in gross phenotypes, compared to the prevailing practice of using displacements of the material points. We conclude that the presented experimental setup and computational pipeline is a viable method that deserves wider application. PMID- 25129022 TI - Exploring the effects of intervention for those at high risk of developing type 2 diabetes using a computer simulation. AB - A simulation based computational method was conducted to reflect the effect of intervention for those at high risk of type 2 diabetes. Hierarchy Support Vector Machines (H-SVMs) were used to classify high risk. The proportion transitioning from the high risk state to moderate state, low state or the normal state was calculated. When Body Mass Index (BMI) decreased by 5% (weight loss 3-5kg), the proportion of Class A transferring to a lower state was 15-25%, and risk also appeared reduced for Class B1. In Class C, when cholesterol (CHOL) was decreased by 2.5% (0.13-0.34mmol/L), 10-25% transitioned to a lower risk state. The method could help determine risk transition by the adjustment of sensitive risk factors. This might provide the basis for implementing intervention in cases in a high risk state. PMID- 25129023 TI - Finding multivariate outliers in fMRI time-series data. AB - A fundamental challenge for researchers studying the brain is to explain how distributed patterns of brain activity relate to a specific representation or computation. Multivariate techniques are therefore becoming increasingly popular for pattern localization of functional magnetic resonance imaging (fMRI) data. The increased power of these techniques can be offset by their susceptibility to multivariate outliers, a problem not directly encountered when fMRI data are analyzed in more common univariate analysis techniques. We test how two algorithms, High Dimensional Blocked Adaptive Computationally Efficient Outlier Nominators (HD BACON) and Principal Component based Outlier detection (PCOut), can detect multivariate outliers in high-dimensional fMRI data, in which the number of variables is larger than the number of observations. We show how these methods can be applied to individual, voxel time-series to identify outlying voxels within a region of interest. Finally, we compare these methods with simulated data to identify which aspects of the data each method is most sensitive to. Voxels identified by both algorithms were primarily on the edges of univariate activation clusters and near the boundaries between different tissue types. Simulation results showed the PCOut outperformed HD BACON, maintaining both high sensitivity and specificity across a wide range of outlier contamination percentages. Our results suggest that multivariate analysis of fMRI can benefit from including multivariate outlier detection as a routine data quality check prior to model fitting. PMID- 25129024 TI - Proximity of premolar roots to maxillary sinus: a radiographic survey using cone beam computed tomography. AB - INTRODUCTION: The proximity of the roots of the posterior maxillary teeth to the maxillary sinus is a constant challenge to the dental practitioner. Because the majority of studies have assessed the relationship regarding molars, the present study focused on premolars. METHODS: Cone-beam computed tomographic images of 192 patients were reconstructed in sagittal, coronal, and axial planes to quantify the distances between the root apices of the maxillary premolars and the adjacent maxillary sinus. Measurements were taken for each root, and data were correlated with age, sex, side, and presence of both or absence of 1 of the 2 premolars. RESULTS: A total of 296 teeth (177 first and 119 second premolars) were evaluated. The mean distances from buccal roots of the first premolars to the border of the maxillary sinus in the sagittal, coronal, and axial planes ranged from 5.15 +/- 2.99 to 8.28 +/- 6.27 mm. From palatal roots, the mean distances ranged from 4.20 +/- 3.69 to 7.17 +/- 6.14 mm. The mean distances of second premolars were markedly shorter in buccal roots between 2.32 +/- 2.19 and 3.28 +/ 3.17 mm and in palatal roots between 2.68 +/- 3.58 and 3.80 +/- 3.71 mm, respectively. The frequency of a premolar root protrusion into the maxillary sinus was very low in first premolars (0%-7.2%) but higher in second premolars (2.5%-13.6%). Sex, age, side, and presence/absence of premolars failed to significantly influence the mean distances between premolar roots and the maxillary sinus. CONCLUSIONS: Based on the calculated mean distances of the present study, only few premolars (and if so second premolars) would present a risk of violating the border of the maxillary sinus during conventional or surgical endodontic treatment or in case of tooth extraction. PMID- 25129026 TI - Assessment of the mechanical properties of ProTaper Next Nickel-titanium rotary files. AB - INTRODUCTION: The purpose of this study was to compare the torsional resistance, flexibility, and surface microhardness of ProTaper Next files (PTN) with Twisted Files (TF) and RaCe (RC). METHODS: A metal block with a cubical hole was used to evaluate the torsional resistance. Five millimeters of the tip of each file was securely held in place by filling the mold with a resin composite, and the files were driven clockwise at 300 rpm. The number of load applications before fracture was recorded for each file. A scanning electron microscope was used to characterize the topographic features of the fracture surfaces of the broken files. The files were tested for bending resistance by using cantilever-bending test. Vickers microhardness was measured on the cross section of instruments with 300-g load and 15-second dwell time. Torsional resistance data were analyzed by using the nonparametric Kruskal-Wallis and Mann-Whitney U tests. Bending resistance and microhardness data were analyzed by using analysis of variance and Tukey tests. RESULTS: PTN showed the highest torsional resistance and microhardness, followed by RC (P < .05). The fracture cross sections of all brands showed dimpling near the center of fracture surface. The ranking in the bending resistance values was as follows: RC > PTN > TF. CONCLUSIONS: PTN improved its resistance to torsional stresses and wear compared with TF and RC. TF showed improved flexibility compared with other tested brands. PMID- 25129025 TI - Zinc incorporation improves biological activity of beta-tricalcium silicate resin based cement. AB - INTRODUCTION: Matrix metalloproteinase (MMP) inhibition may improve endodontic treatment prognosis. The purpose of this study was to determine if zinc incorporation into experimental resin cements containing bioactive fillers may modulate MMP-mediated collagen degradation of dentin. METHODS: Human dentin samples untreated and demineralized using 10% phosphoric acid or 0.5 mol/L EDTA were infiltrated with the following experimental resins: (1) unfilled resin, (2) resin with Bioglass 45S5 particles (OSspray, London, UK), (3) resin with beta tricalcium silicate particles (betaTCS), (4) resin with zinc-doped Bioglass 45S5, and (5) resin with zinc-doped betaTCS particles. The specimens were stored in artificial saliva (for 24 hours, 1 week, and 4 weeks) and submitted to radioimmunoassay to quantify C-terminal telopeptide. Scanning electron microscopy analysis was also undertaken on dentin samples after 4 weeks of storage. RESULTS: Collagen degradation was prominent both in phosphoric acid and EDTA-treated dentin. Resin infiltration strongly reduced MMP activity in demineralized dentin. Resin containing Bioglass 45S5 particles exerted higher and stable protection of collagen. The presence of zinc in betaTCS particles increases MMP inhibition. Different mineral precipitation was attained in dentin infiltrated with the resin cements containing bioactive fillers. CONCLUSIONS: MMP degradation of dentin collagen is strongly reduced after resin infiltration of dentin. Zinc incorporation in betaTCS particles exerted an additional protection against MMP mediated collagen degradation. However, it did not occur in resin containing Bioglass 45S5 particles, probably because of the formation of phosphate-zinc compounds. PMID- 25129027 TI - Psychometric evaluation of the child PTSD symptom scale in Spanish and English. AB - Given the consistent growth of the Latino population in the United States, there is a critical need for validated Spanish measures to assess posttraumatic stress disorder (PTSD) symptoms in children. The current study examines the psychometric properties of the Child PTSD Symptom Scale (CPSS). We examined 259 children (8-17 years) who had experienced a recent traumatic event. Study measures were completed in Spanish (n = 106; boys = 58, girls = 48) or in English (n = 153; boys = 96, girls = 57). In addition to internal consistency, confirmatory factor analyses were conducted by testing four models to examine construct validity: (1) PTS single-factor, (2) DSM-IV three-factor, (3) Numbing four-factor, and (4) Dysphoria four-factor models. Findings demonstrated good internal consistency for both the English and Spanish versions of the CPSS. The English version revealed superior fit to the data for several models of PTS symptoms structure compared to the Spanish version. The current study demonstrated construct validity for the English CPSS, but not for the Spanish CPSS. Future studies will examine additional alternative models as well as convergent and discriminant validity of the Spanish CPSS. PMID- 25129028 TI - Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis. AB - Despite intensive research, the cyclodehydratase responsible for azoline biogenesis in thiazole/oxazole-modified microcin (TOMM) natural products remains enigmatic. The collaboration of two proteins, C and D, is required for cyclodehydration. The C protein is homologous to E1 ubiquitin-activating enzymes, whereas the D protein is within the YcaO superfamily. Recent studies have demonstrated that TOMM YcaOs phosphorylate amide carbonyl oxygens to facilitate azoline formation. Here we report the X-ray crystal structure of an uncharacterized YcaO from Escherichia coli (Ec-YcaO). Ec-YcaO harbors an unprecedented fold and ATP-binding motif. This motif is conserved among TOMM YcaOs and is required for cyclodehydration. Furthermore, we demonstrate that the C protein regulates substrate binding and catalysis and that the proline-rich C terminus of the D protein is involved in C protein recognition and catalysis. This study identifies the YcaO active site and paves the way for the characterization of the numerous YcaO domains not associated with TOMM biosynthesis. PMID- 25129029 TI - Engineered oligosaccharyltransferases with greatly relaxed acceptor-site specificity. AB - The Campylobacter jejuni protein glycosylation locus (pgl) encodes machinery for asparagine-linked (N-linked) glycosylation and serves as the archetype for bacterial N-linked glycosylation. This machinery has been functionally transferred into Escherichia coli, enabling convenient mechanistic dissection of the N-linked glycosylation process in this genetically tractable host. Here we sought to identify sequence determinants in the oligosaccharyltransferase PglB that restrict its specificity to only those glycan acceptor sites containing a negatively charged residue at the -2 position relative to asparagine. This involved creation of a genetic assay, glycosylation of secreted N-linked acceptor proteins (glycoSNAP), that facilitates high-throughput screening of glycophenotypes in E. coli. Using this assay, we isolated several C. jejuni PglB variants that could glycosylate an array of noncanonical acceptor sequences, including one in a eukaryotic N-glycoprotein. These results underscore the utility of glycoSNAP for shedding light on poorly understood aspects of N-linked glycosylation and for engineering designer N-linked glycosylation biocatalysts. PMID- 25129031 TI - Characteristics of MPO-ANCA-positive granulomatosis with polyangiitis: a retrospective multi-center study in Japan. AB - We studied the clinico-pathological differences among PR3-ANCA-positive granulomatosis with polyangiitis (PR3-GPA), MPO-ANCA-positive GPA (MPO-GPA) and microscopic polyangiitis (MPA). ANCA-associated vasculitis (AAV) was classified using the European Medicines Agency classification. We retrospectively analyzed 38 patients with GPA and 41 with MPA treated in eight hospitals in Japan. Of the patients with GPA, 17 were positive for MPO-ANCA, and 15 for PR3-ANCA. All patients with MPA were MPO-ANCA positive. The mean ages of those with MPO-GPA were 69.6 years old, 10 years older than those with PR3-GPA. The majority (82 %) of patients with MPO-GPA were woman, a significantly greater proportion than for PR3-GPA. We also found that ear, nose and throat (ENT), nervous system involvement were significantly more common in MPO-GPA, but renal function was less impaired than those with MPA. Both PR3-GPA and MPO-GPA relapsed more frequently than MPA, but overall survival was significantly better (P < 0.01 and P < 0.05, respectively). Univariate analysis identified the following factors as predictors of a poor prognosis: MPA (P < 0.01), pulmonary UIP pattern (P < 0.005) Cr >= 1.7 mg/dl (P < 0.01) and absence of ENT involvement (P < 0.05), which were characteristics of MPA. In our cohort, MPO-GPA was most likely to affect older women and was associated with otitis media, nervous system involvement, mild renal impairment and more favorable outcome. It is clinically useful to differentiate MPO-GPA from MPA and PR3-GPA in patients with AAV. PMID- 25129030 TI - A chemical inhibitor of jasmonate signaling targets JAR1 in Arabidopsis thaliana. AB - Jasmonates are lipid-derived plant hormones that regulate plant defenses and numerous developmental processes. Although the biosynthesis and molecular function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile), have been unraveled, it remains poorly understood how the diversity of bioactive jasmonates regulates such a multitude of plant responses. Bioactive analogs have been used as chemical tools to interrogate the diverse and dynamic processes of jasmonate action. By contrast, small molecules impairing jasmonate functions are currently unknown. Here, we report on jarin-1 as what is to our knowledge the first small-molecule inhibitor of jasmonate responses that was identified in a chemical screen using Arabidopsis thaliana. Jarin-1 impairs the activity of JA-Ile synthetase, thereby preventing the synthesis of the active hormone, JA-Ile, whereas closely related enzymes are not affected. Thus, jarin-1 may serve as a useful chemical tool in search for missing regulatory components and further dissection of the complex jasmonate signaling networks. PMID- 25129032 TI - Association of abuse history with symptom severity and quality of life in patients with fibromyalgia. AB - A high prevalence of abuse has been reported in patients with fibromyalgia. We aimed to examine the association between self-reported abuse history and symptom severity and quality of life (QOL) in 962 patients with fibromyalgia. All patients completed the Fibromyalgia Impact Questionnaire (FIQ) and the Short Form 36 health survey (SF-36). Multivariate regression analyses were performed. In total, 289 patients (30%) reported a history of abuse. Of those who specified abuse types, 161 patients (59%) reported more than 1 type of abuse (36% emotional, 32% physical, 25% sexual, and 7% verbal). Patients in the abuse group were younger and more likely to be female, unemployed, unmarried, and current smokers compared with patients who reported no abuse. After adjusting for these differences, abuse history was associated with worse symptoms, as indicated by a higher FIQ total score (P < .001) and higher FIQ subscale scores in physical function (P = .001), work missed (P < .001), job ability (P < .001), pain (P = .02), depression (P < .001), and anxiety (P < .001). Similarly, abuse history was associated with worse QOL, with lower SF-36 scores in all domains except the physical component summary. In conclusion, abuse history in patients with fibromyalgia was associated with worse symptoms and QOL compared with those patients without abuse history. Future studies are needed to assess whether additional tailored interventions as part of fibromyalgia treatment are helpful for patients with a history of abuse. PMID- 25129033 TI - Ultrasound, anthropometry and bioimpedance: a comparison in predicting fat deposition in non-alcoholic fatty liver disease. AB - PURPOSE: The aim of our study was the evaluation of anthropometric measurements [waist circumference and sagittal abdominal diameter (SAD)] and abdominal bioelectrical impedance analysis (BIA) (ViScan, TANITA) in comparison to several abdominal ultrasonographic (US) measurements to estimate visceral fat deposition and liver steatosis in a population of 105 subjects. METHODS: All 105 patients underwent a complete anthropometric evaluation, blood sample for the determination of total cholesterol, HDL cholesterol, triglycerides, glucose, insulin, high-sensitivity C-reactive protein, BIA and US measurements (peritoneal, pre-peritoneal, peri-renal, para-renal and peri-hepatic fat thickness). RESULTS: All the ultrasonographic markers considered in our study are related to the presence of non-alcoholic fatty liver disease (NAFLD), and so is true for SAD. Comparing ROC curves, peritoneal fat tissue thickness, SAD and ViScan visceral index are significantly better than waist circumference in predicting the presence of NAFLD (AUC 0.79 +/- 0.04; 0.81 +/- 0.05; 0.82 +/- 0.04 vs 0.76 +/- 0.05, respectively). CONCLUSIONS: According to our data, various methods may be useful in evaluating NAFLD, but only ViScan visceral index, US peritoneal fat thickness and SAD are better than waist circumference. Among them, SAD is the most promising, due to its small cost and time consumption. PMID- 25129035 TI - Anger superiority effect for change detection and change blindness. AB - In visual search, an angry face in a crowd "pops out" unlike a happy or a neutral face. This "anger superiority effect" conflicts with views of visual perception holding that complex stimulus contents cannot be detected without focused top down attention. Implicit visual processing of threatening changes was studied by recording event-related potentials (ERPs) using facial stimuli using the change blindness paradigm, in which conscious change detection is eliminated by presenting a blank screen before the changes. Already before their conscious detection, angry faces modulated relatively early emotion sensitive ERPs when appearing among happy and neutral faces, but happy faces only among neutral, not angry faces. Conscious change detection was more efficient for angry than happy faces regardless of background. These findings indicate that the brain can implicitly extract complex emotional information from facial stimuli, and the biological relevance of threatening contents can speed up their break up into visual consciousness. PMID- 25129036 TI - Complex continuous wavelet coherence for EEG microstates detection in insight and calm meditation. AB - Complex continuous wavelet coherence (WTC) can be used for non-stationary signals, such as electroencephalograms. Areas of the WTC with a coherence higher than the calculated optimal threshold were obtained, and the sum of their areas was used as a criterion to differentiate between groups of experienced insight focused meditators, calm-focused meditators and a control group. This method demonstrated the highest accuracy for the real WTC parts in the frontal region, while for the imaginary parts, the highest accuracy was shown for the frontal occipital pairs of electrodes. In the frontal area, in the broadband frequency, both types of experienced meditators demonstrated an enlargement of the increased coherence areas for the real WTC parts. For the imaginary parts unaffected by the volume conduction and global artefacts, the most significant increase occurred for the frontal occipital pair of electrodes. PMID- 25129034 TI - Apoptosis of Purkinje and granular cells of the cerebellum following chronic ethanol intake. AB - Ethanol alters motricity, learning, cognition, and cellular metabolism in the cerebellum. We evaluated the effect of ethanol on apoptosis in Golgi, Purkinje, and granule cells of the cerebellum in adult rats. There were two groups of 20 rats: a control group that did not consume ethanol and an experimental group of UChA rats that consumed ethanol at 10% (<2 g ethanol/kg body weight/day). At 120 days old, rats were anesthetized and decapitated, and their cerebella were collected and fixed. Cerebellar sections were subjected to immunohistochemistry for terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), caspase 3, X-linked inhibitor of apoptosis protein (XIAP), and insulin-like growth factor 1-receptor (IGF-1R); real-time PCR (RT-PCR) to determine caspase-3, XIAP, and IGF 1R gene expression; and transmission electron microscopy (TEM). We identified fragmentation of DNA and an increase in caspase-3 protein and XIAP in Purkinje cells, whereas granule cells exhibited increased caspase-3 and XIAP. IGF-1R expression was unchanged. There was no significant difference in gene expression of caspase-3, XIAP, and IGF-1R. There were an increase in lipid droplets, a reduction in the cellular cytoplasm in electron-dense nuclei, and changes in the myelin sheath in the cerebellar cortex. In conclusion, our data demonstrated that ethanol induced apoptosis in the Purkinje and granule cells of the cerebellum of adult UChA rats. PMID- 25129037 TI - The cognitive antecedents and motivational consequences of the feeling of being in the zone. AB - The feeling of being in the zone (related to "flow") is marked by an elevated yet effortless sense of concentration. Prior research suggests that feelings of being in the zone are strongest when the demand posed by a task matches one's level of ability (i.e., the balance hypothesis). In the present article, we tested this hypothesis using a novel experimental paradigm. By collecting numerous zone judgments for each participant, we were able to examine intra-individual sources of variance that explain why people often feel more or less in-the-zone on the same task from one moment to the next. The results of two experiments provide support for what we have termed the balance-plus hypothesis, which posits that zone experiences are strongest (Experiments 1-2) and have the greatest motivational force (Experiment 2) when the balance between task demand and ability is accompanied by positive assessments of one's own performance. PMID- 25129039 TI - Cellulolytic and xylanolytic potential of high beta-glucosidase-producing Trichoderma from decaying biomass. AB - Availability, cost, and efficiency of microbial enzymes for lignocellulose bioconversion are central to sustainable biomass ethanol technology. Fungi enriched from decaying biomass and surface soil mixture displayed an array of strong cellulolytic and xylanolytic activities. Strains SG2 and SG4 produced a promising array of cellulolytic and xylanolytic enzymes including beta glucosidase, usually low in cultures of Trichoderma species. Nucleotide sequence analysis of internal transcribed spacer 2 (ITS2) region of rRNA gene revealed that strains SG2 and SG4 are closely related to Trichoderma inhamatum, Trichoderma piluliferum, and Trichoderma aureoviride. Trichoderma sp. SG2 crude culture supernatant correspondingly displayed as much as 9.84 +/- 1.12, 48.02 +/- 2.53, and 30.10 +/- 1.11 units mL(-1) of cellulase, xylanase, and beta glucosidase in 30 min assay. Ten times dilution of culture supernatant of strain SG2 revealed that total activities were about 5.34, 8.45, and 2.05 orders of magnitude higher than observed in crude culture filtrate for cellulase, xylanase, and beta-glucosidase, respectively, indicating that more enzymes are present to contact with substrates in biomass saccharification. In parallel experiments, Trichoderma species SG2 and SG4 produced more beta-glucosidase than the industrial strain Trichoderma reesei RUT-C30. Results indicate that strains SG2 and SG4 have potential for low cost in-house production of primary lignocellulose hydrolyzing enzymes for production of biomass saccharides and biofuel in the field. PMID- 25129040 TI - Detergent-compatible bacterial amylases. AB - Proteases, lipases, amylases, and cellulases are enzymes used in detergent formulation to improve the detergency. The amylases are specifically supplemented to the detergent to digest starchy stains. Most of the solid and liquid detergents that are currently manufactured contain alkaline enzymes. The advantages of using alkaline enzymes in the detergent formulation are that they aid in removing tough stains and the process is environmentally friendly since they reduce the use of toxic detergent ingredients. Amylases active at low temperature are preferred as the energy consumption gets reduced, and the whole process becomes cost-effective. Most microbial alkaline amylases are used as detergent ingredients. Various reviews report on the production, purification, characterization, and application of amylases in different industry sectors, but there is no specific review on bacterial or fungal alkaline amylases or detergent compatible amylases. In this mini-review, an overview on the production and property studies of the detergent bacterial amylases is given, and the stability and compatibility of the alkaline bacterial amylases in the presence of the detergents and the detergent components are highlighted. PMID- 25129038 TI - Using familial information for variant filtering in high-throughput sequencing studies. AB - High-throughput sequencing studies (HTS) have been highly successful in identifying the genetic causes of human disease, particularly those following Mendelian inheritance. Many HTS studies to date have been performed without utilizing available family relationships between samples. Here, we discuss the many merits and occasional pitfalls of using identity by descent information in conjunction with HTS studies. These methods are not only applicable to family studies but are also useful in cohorts of apparently unrelated, 'sporadic' cases and small families underpowered for linkage and allow inference of relationships between individuals. Incorporating familial/pedigree information not only provides powerful filtering options for the extensive variant lists that are usually produced by HTS but also allows valuable quality control checks, insights into the genetic model and the genotypic status of individuals of interest. In particular, these methods are valuable for challenging discovery scenarios in HTS analysis, such as in the study of populations poorly represented in variant databases typically used for filtering, and in the case of poor-quality HTS data. PMID- 25129041 TI - An anisakis larva attached to early gastric cancer: report of a case. AB - Gastrointestinal anisakidosis is a nematode infection caused by the ingestion of larvae-infected raw or undercooked fish. The Japanese like to eat raw or undercooked fish, so gastric anisakiasis is a common disease in Japan. However, reports of anisakiasis with gastrointestinal cancer are rare. A 63-year-old Japanese male was diagnosed with a small early gastric cancerous lesion associated with gastric anisakiasis. From our experience and based on a review of the literature, the attachment of an anisakis larva to early gastric cancer is not considered accidental. PMID- 25129042 TI - DPP6 gene disruption in a family with Gilles de la Tourette syndrome. AB - Gilles de la Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor and vocal tics, frequently associated with psychiatric co-morbidities. Despite the significant level of heritability, the genetic architecture of TS still remains elusive. Herein, we investigated an Italian family where an 8-year-old boy, his father, and paternal uncle have a diagnosis of TS. Array-CGH and high resolution SNP-array analyses revealed a heterozygous microdeletion of ~135 kb at the 7q36.2 locus in the proband and his father. Fluorescent in situ hybridization and quantitative PCR (qPCR) analyses confirmed the presence of the alteration also in the paternal uncle. The deletion selectively involves the first exon of the DPP6 gene, leading to a down regulation of its expression, as demonstrated by the reduced messenger RNA (mRNA) levels assessed by RT-qPCR. The DPP6 gene encodes for a type II membrane glycoprotein expressed predominantly in the central nervous system. To date, a de novo DPP6 exonic duplication, of uncertain significance, was reported in one patient with TS. Moreover, the DPP6 gene has been implicated in the pathogenesis of autism spectrum disorder (ASD) and, notably, in haloperidol-induced dyskinesia. This first familial case provides evidence for association between DPP6 haploinsufficiency and TS, further suggesting a plausible molecular link between TS and ASD, and might shed some light on the efficacy and tolerability profiles of antidopaminergic agents used for tic management, thus prompting further studies on a larger cohort of patients. PMID- 25129043 TI - Malignant dysphagia treated by esophageal sparing surgery with good prognosis. PMID- 25129045 TI - Microbial lipid production: screening with yeasts grown on Brazilian molasses. AB - Rhodotorula glutinis CCT 2182, Rhodosporidium toruloides CCT 0783, Rhodotorula minuta CCT 1751 and Lipomyces starkeyi DSM 70296 were evaluated for the conversion of sugars from Brazilian molasses into single-cell oil (SCO) feedstock for biodiesel. Pulsed fed-batch fermentations were performed in 1.65 l working volume bioreactors. The maximum specific growth rate (umax), lipid productivity (Pr) and cellular lipid content were, respectively, 0.23 h(-1), 0.41 g l(-1) h( 1), and 41% for Rsp. toruloides; 0.20 h(-1), 0.27 g l(-1) h(-1), and 36% for Rta. glutinis; 0.115 h(-1), 0.135 g l(-1) h(-1), and 27 % for Rta. minuta; and 0.11 h( 1), 0.13 g l(-1) h(-1), and 32% for L. starkeyi. Based on their microbial lipid productivity, content, and profile, Rsp. toruloides and Rta. glutinis are promising candidates for biodiesel production from Brazilian molasses. All the oils from the yeasts were similar to the composition of plant oils (rapeseed and soybean) and could be used as raw material for biofuels, as well as in food and nutraceutical products. PMID- 25129046 TI - Pretreatment with mechano-growth factor E peptide protects bone marrow mesenchymal cells against damage by fluid shear stress. AB - Improper fluid shear stress (FSS) can cause serious damages to bone marrow mesenchymal stem cells (MSCs). Mechano-growth factor (MGF) E peptide pretreatment was proposed to protect MSCs against FSS damage in this study. MSCs were exposed to FSS for 30 min after they were pretreated with MGF E peptide for 24 h. Then, the effects of MGF E peptide on the viability, proliferation and cell apoptosis of MSCs were investigated. MGF E peptide pretreatment could recover the cellular metabolic activity of MSCs reduced by 72 dyne cm(-2) FSS and had a synergistic effect with FSS on the cellular metabolic viability of MSCs under 24 and 72 dyne cm(-2) FSS. These results suggested that MGF E peptide pretreatment could be an effective method for the protection of FSS damage in bone tissue engineering. PMID- 25129044 TI - More than spikes: common oscillatory mechanisms for content specific neural representations during perception and memory. AB - Although previous research into the mechanisms underlying sensory and episodic representations has primarily focused on changes in neural firing rate, more recent evidence suggests that neural oscillations also contribute to these representations. Here, we argue that multiplexed oscillatory power and phase contribute to neural representations at the mesoscopic scale, complementary to neuronal firing. Reviewing recent studies which used oscillatory activity to decipher content-specific neural representations, we identify oscillatory mechanisms common to both sensory and episodic memory representations and incorporate these into a model of episodic encoding and retrieval. This model advances the idea that oscillations provide a reference frame for phase-coded item representations during memory encoding and that shifts in oscillatory frequency and phase coordinate ensemble activity during memory retrieval. PMID- 25129047 TI - Regioselective hydroxylation of 17beta-estradiol by mutants of CYP102A1 from Bacillus megaterium. AB - A large set of mutants of CYP102A1 from Bacillus megaterium have human cytochrome P450-like activities and the ability to metabolize a number of marketed drugs and steroids. Here, we tested whether the CYP102A1 mutants could be used to produce hydroxylated human metabolites of 17beta-estradiol (E2). A set of the mutants, which were generated by site-directed and random mutagenesis, was used to produce hydroxylated human metabolites of E2 in this study. Some of the tested mutants could regioselectively generate 2-OH E2 as a major metabolite but not other hydroxylated products. These results suggest that CYP102A1 mutants would be useful for the bioconversion of steroid hormones to hydroxylated products, which can be used for industrial applications. PMID- 25129048 TI - Probing the bioethanol production potential of Scheffersomyces (Pichia) stipitis using validated genome-scale model. AB - A detailed in silico analysis of different strategies for enhancement of bioethanol production by Scheffersomyces stipitis, = Pichia stipitis, using validated genome-scale metabolic model is presented. Glucose inhibition on xylose uptake is dominant in S. stipitis which makes fed-batch fermentation more effective for higher sugar concentrations. Bioethanol production potential of S. stipitis can be improved by growth media modification by introducing certain amino acids in small quantities. Slower sugar uptake by S. stipitis can be overcome by community-culture with recombinant Escherichia coli strain ZSC113, which has a higher xylose uptake rate. Ethanol yield and productivity of community-culture can be further enhanced by genetic modification of E. coli strain ZSC113. PMID- 25129049 TI - Secretory expression of a bispecific antibody targeting tumor necrosis factor and ED-B fibronectin in Pichia pastoris and its functional analysis. AB - Specific targeting of tumor necrosis factor (TNF)-alpha antagonist to the inflamed site could increase its efficacy and reduce side-effects. Here, we constructed a bispecific diabody (BsDb) that targets TNF-alpha and ED-B containing fibronectin, a fibronectin isoform specifically expressed in the pannus of the inflamed synovium in rheumatoid arthritis. BsDb was secreted from Pichia pastoris as functional protein and was purified to homogeneity. BsDb could simultaneously bind to human TNF-alpha and B-FN and neutralize TNF-alpha action. Additionally, BsDb showed a significant gain both in the antigen-binding affinity and in TNF-alpha-neutralizing ability as compared to its original antibodies, L19 and anti-TNF-alpha scFv, which were produced in E. coli. BsDb was constructed and was endowed with enhanced bioactivities and improved production processing. Therefore, it holds great potential for in vivo applications. PMID- 25129050 TI - Structural analysis of cerebrosides from Aspergillus fungi: the existence of galactosylceramide in A. oryzae. AB - Glucosylceramide and galactosylceramide were detected in three Aspergillus species: Aspergillus oryzae, Aspergillus sojae and Aspergillus. awamori, using borate-coated TLC. The cerebrosides from A. oryzae were further purified by ion exchange and iatrobeads column chromatographies with or without borate, and determined the composition of sugar, fatty acid and sphingoid base by GC/MS, MALDI-TOF/MS and (1)H-NMR. We identified them as beta-glucosylceramide and beta galactosylceramide. The ceramide moiety of both cerebrosides consisted mainly of 2-hydroxystearic acid and either 9-methyl-octadeca-4, 8-sphingadienine or octadeca-4, 8-sphingadienine. To our knowledge, this is the first study to provide evidence for the presence of beta-galactosylceramide in A. oryzae. PMID- 25129051 TI - Comparative effects of technical-grade and a commercial formulation of glyphosate on the pigment content of periphytic algae. AB - We investigated the potentially different effects of one of the most commonly used glyphosate formulations in Argentina, Glifosato Atanor((r)), and the technical-grade glyphosate on the pigment content, as biomass indicators of the algal fraction in a freshwater periphytic community. A laboratory bioassay was carried out in 250-ml beakers. Two treatments were used: technical-grade glyphosate acid and Glifosato Atanor((r)) (isopropylamine salt of glyphosate 48 % w/v), which were at a concentration of 3 mg active ingredient per liter. Treatments and the control (without herbicide) were replicated in triplicate. The concentrations of chlorophyll a and b and carotenes were determined at 0, 2, 6, 10, 24, 48, 96 and 192 h after herbicide addition. A significant increase in pigment content was observed for both herbicides after a 2-day exposure. Moreover, the formulation had little or no effect compared to the active ingredient, suggesting that the additives of Glifosato Atanor((r)) may not enhance glyphosate toxicity. PMID- 25129053 TI - Mechanistic modelling of toxicokinetic processes within Myriophyllum spicatum. AB - Effects of chemicals are, in most cases, caused by internal concentrations within organisms which rely on uptake and elimination kinetics. These processes might be key components for assessing the effects of time-variable exposure of chemicals which regularly occur in aquatic systems. However, the knowledge of toxicokinetic patterns caused by time-variable exposure is limited, and gaining such information is complex. In this work, a previously developed mechanistic growth model of Myriophyllum spicatum is coupled with a newly developed toxicokinetic part, providing a model that is able to predict uptake and elimination of chemicals, as well as distribution processes between plant compartments (leaves, stems, roots) of M. spicatum. It is shown, that toxicokinetic patterns, at least for most of the investigated chemicals, can be calculated in agreement with experimental observations, by only calibrating two chemical- specific parameters, the cuticular permeability and a plant/water partition coefficient. Through the model-based determination of the cuticular permeabilities of Isoproturon, Iofensulfuron, Fluridone, Imazamox and Penoxsulam, their toxicokinetic pattern can be described with the model approach. For the use of the model for predicting toxicokinetics of other chemicals, where experimental data is not available, equations are presented that are based on the log (P oct/wat) of a chemical and estimate parameters that are necessary to run the model. In general, a method is presented to analyze time-variable exposure of chemicals more in detail without conducting time and labour intensive experiments. PMID- 25129052 TI - Epidemiology of MPN: what do we know? AB - The myeloproliferative neoplasms, are characterised by overproduction of myeloid cells. Chronic myeloid leukaemia, polycythaemia vera, essential thrombocythaemia, myelofibrosis and the very rare disorders chronic neutrophilic leukaemia, chronic eosinophilic leukaemia not otherwise specified and mastocytosis are all included in the group. Incidence and prevalence rates reported in the worldwide literature are presented in this review. Survival data on each condition is described. Information on the aetiology of the disorders is discussed including body mass index, diet, smoking and alcohol, allergies, associated medical conditions, occupation and environmental exposures with focus on recent new studies. The aetiology of the myeloproliferative neoplasms remains unknown, and this review of the current state of knowledge highlights the need for further comprehensive research. PMID- 25129054 TI - The use of the EQ-5D as a measure of health-related quality of life in people with dementia and their carers. AB - PURPOSE: To assess the acceptability, validity and inter-rater agreement of self- and family carer proxy ratings of the EQ-5D as a generic health-related quality of life (HRQOL) measure, in people with mild to moderate dementia (PwD) living in the community. A secondary aim was to identify the most important factors influencing self- and family carer proxy ratings of HRQOL, distinguishing between spouse and adult child caregiver ratings. METHODS: Cross-sectional study of 488 dyads using the EQ-5D. Inter-rater agreement was examined using weighted kappa scores, and validity by investigating the association of self- and family carer ratings with clinical variables. Factors affecting HRQOL ratings were analysed using multivariate regression. RESULTS: The response rate of the EQ-5D was satisfactory; however, agreement between self- and family carer ratings was poor. The most important predictors of PwD and carer ratings of the PwD's HRQOL were family carer ratings of activities of daily living and mood. Anxiety experienced by the PwD was a significant predictor of self-rated HRQOL, whereas depressive symptoms independently predicted family carer ratings. The type of the caregiving relationship influenced carer ratings of HRQOL, whereby sons and daughters rated HRQOL lower for the PwD compared with spousal caregivers. CONCLUSIONS: People with mild to moderate dementia are able to rate their own HRQOL through a brief generic instrument; however, self-ratings consistently differ from family carer ratings, which should be acknowledged in cost-effectiveness analyses. Spouse caregivers rate HRQOL for the PwD more positively compared to adult children. PMID- 25129055 TI - Ligand-directed tosyl chemistry for in situ native protein labeling and engineering in living systems: from basic properties to applications. AB - The ability to introduce any chemical probe to any endogenous target protein in its native environment, that is in cells and in vivo, is anticipated to provide various new exciting tools for biological and biomedical research. Although still at the prototype stage, the ligand-directed tosyl (LDT) chemistry is a novel type of affinity labeling technique that we developed for such a dream. This chemistry allows for modifying native proteins by various chemical probes with high specificity in various biological settings ranging from in vitro (in test tubes) to in living cells and in vivo. Since the first report, the list of proteins that are successfully labeled by the LDT chemistry has been increasing. A growing number of studies have demonstrated its utility to create semisynthetic proteins directly in cellular contexts. The in situ generated semisynthetic proteins are applicable for various types of analysis and imaging of intracellular biological processes. In this review, we summarize the basic properties of the LDT chemistry and its applications toward in situ engineering and analysis of native proteins in living systems. Current limitations and future challenges of this area are also described. PMID- 25129056 TI - Turning the spotlight on protein-lipid interactions in cells. AB - Protein function is largely dependent on coordinated and dynamic interactions of the protein with biomolecules including other proteins, nucleic acids and lipids. Although powerful methods for global profiling of protein-protein and protein nucleic acid interactions are available, proteome-wide mapping of protein-lipid interactions is still challenging and rarely performed. The emergence of bifunctional lipid probes with photoactivatable and clickable groups offers new chemical tools for globally profiling protein-lipid interactions under cellular contexts. In this review, we summarize recent advances in the development of bifunctional lipid probes for studying protein-lipid interactions. We also highlight how in vivo photocrosslinking reactions contribute to the characterization of lipid-binding proteins and lipidation-mediated protein protein interactions. PMID- 25129057 TI - The role of mitochondrial reactive oxygen species in cartilage matrix destruction. AB - Upregulation of matrix metalloproteinases (MMPs) is a hallmark of osteoarthritis progression; along with the role reactive oxygen species (ROS) may play in this process. Moreover, mitochondrial DNA damage and dysfunction are also present in osteoarthritic chondrocytes. However, there are no studies published investigating the direct relationship between mitochondrial ROS, mitochondrial DNA damage, and MMP expression. Therefore, the purpose of the present study was to evaluate whether mitochondrial DNA damage and mitochondrial-originated oxidative stress modulates matrix destruction through the upregulation of MMP protein levels. MitoSox red was utilized to observe mitochondrial ROS production while a Quantitative Southern blot technique was conducted to analyze mitochondrial DNA damage. Additionally, Western blot analysis was used to determine MMP protein levels. The results of the present study show that menadione augmented mitochondrial-generated ROS and increased mitochondrial DNA damage. This increase in mitochondrial-generated ROS led to an increase in MMP levels. When a mitochondrial ROS scavenger was added, there was a subsequent reduction in MMP levels. These studies reveal that mitochondrial integrity is essential for maintaining the cartilage matrix by altering MMP levels. This provides new and important insights into the role of mitochondria in chondrocyte function and its potential importance in therapeutic approaches. PMID- 25129058 TI - Pemetrexed ameliorates experimental arthritis in rats. AB - Pemetrexed (PMTX) is an anti-folate drug as methotrexate. The purpose of this study was to assess the efficacy of PMTX on collagen-induced arthritis (CIA). Forty Wistar albino rats were randomized into four groups. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant. Animals were sacrificed at the 15th day after the onset of arthritis. Tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-17, and malondialdehyde (MDA) levels were increased, and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were decreased in the arthritis group. In the PMTX-treated (0.2 and 1 mg/kg/week i.p.) groups, the levels of TNF-alpha, IL-17, and MDA were decreased; the activities of SOD, CAT, and GPx and the expressions of Nrf2 and HO-1 were restored, and perisynovial inflammation and cartilage-bone destruction were decreased. PMTX has anti-arthritic potential in the CIA model and may be a therapeutic agent for rheumatoid arthritis. PMID- 25129059 TI - Expression of CXCR1 (interleukin-8 receptor) in murine macrophages after staphylococcus aureus infection and its possible implication on intracellular survival correlating with cytokines and bacterial anti-oxidant enzymes. AB - Interaction with the live Staphylococcus aureus promotes secretion of interleukin 8 (IL-8), although the expressions of functional CXCR1 (IL-8RA) in murine macrophages have not been identified. Expression of CXCR1 was induced in S. aureus-infected macrophages, whereas, CXCR1 was undetectable in control macrophages. CXCR1 blocking significantly reduced the phagocytosis of S. aureus and TNF-alpha, IL-6, IL-1beta, IFN-gamma, IL-12, and IL-8 production and increased release of MIP-2 and soluble TNF-R1. Increased bacterial catalase and decreased superoxide dismutase (SOD) activities by S. aureus with concomitant decrease in hydrogen peroxide (H2O2), superoxide anion, and nitric oxide (NO) release were observed in case of prior CXCR1 blocking. In the presence of cytochalasin D, S. aureus-mediated induction of IL-8 was inhibited concomitant with decreased bacterial count suggesting that internalization of S. aureus was necessary for induction of IL-8. Shedding of TNF-R1 due to CXCR1 blocking after S. aureus inoculation was critical for neutralization of TNF-alpha signaling and arrests the inflammation. PMID- 25129061 TI - Separation of cis- and trans-cypermethrin by reversed-phase high-performance liquid chromatography. AB - As a pyrethroid insecticide, cypermethrin (CP) possesses three chiral centers and thus consists of eight optical isomers. High-performance liquid chromatography (HPLC) methods have been established for the separation and determination of pyrethroid insecticides. In this article, we report a new reversed-phase high performance liquid chromatography (RP-HPLC) method of separating the diastereomers of CP. Our method was performed on a C18 column with the following specifications: mobile phase, methanol/acetonitrile/water (58:18:24, v/v/v); flow rate, 1.0 mL/min; column temperature, 20 degrees C and UV-detection wavelength, 235 nm. The results showed that the applied procedure was linear based on calibration curves with equation (y = 16.595x + 1.7892) within the CP concentration range of 5-100 mg/L. The limit of detection and limit of quantification of CP were 0.2 and 0.7 mg/L, respectively. CP or beta-CP extracted from the microbial degradation system was determined, and the method was proved to be accurate and applicable. Therefore, the proposed RP-HPLC method was simple, inexpensive and can be used to study stability and determine CP residues in pharmaceutical preparations or in the environment. PMID- 25129060 TI - CD86 polymorphism affects pneumonia-induced sepsis by decreasing gene expression in monocytes. AB - Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of morbidity and mortality worldwide. CD86 (B7-2) is a costimulatory molecule on antigen-presenting cells and plays critical roles in immune responses. In the current study, we investigated the association of two CD86 polymorphisms, rs1129055G/A and rs17281995G/C, with susceptibility to pneumonia-induced sepsis and examined the effects of these two polymorphisms on gene expression in monocytes. CD86 rs1129055G/A and rs17281995G/C were identified in 192 pneumonia-induced septic patients and 201 healthy controls. Data showed that frequencies of the rs1129055GA and AA genotypes were significantly lower in patients than in controls (odds ratio [OR]=0.57, 95 % confidence interval [CI], 0.35-0.93, p=0.023, and OR=0.40, 95 % CI, 0.23-0.71, p=0.002). Interestingly, the other polymorphism, rs17281995G/C, revealed significantly increased numbers in pneumonia-induced sepsis compared to controls (OR=1.85, 95 % CI, 1.07-3.20, p=0.025). Further analyses about CD86 gene expression revealed that both messenger RNA (mRNA) and protein levels of CD86 were downregulated in monocytes from controls carrying rs17281995GC genotype than those carrying wild-type rs17281995GG genotype (p=0.022 and p=0013). These results suggest that polymorphisms in CD86 gene have diverse effects on the pathogenesis of pneumonia induced sepsis, in which rs17281995G/C may increase the risk of the disease by interfering gene expression of CD86 in monocytes. PMID- 25129062 TI - Validation of an HPLC-MS/MS and wipe procedure for mitomycin C contamination. AB - A high-performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) method was developed for the determination of mitomycin C, an anticancer drug, from contamination on various surfaces. Mitomycin C is often used in various forms of intraperitoneal chemotherapy, and operating room healthcare worker exposure to this drug is possible. The surface testing method consisted of a wiping procedure utilizing a solution of 20/45/35 (v/v/v) of acetonitrile isopropanol-water made 0.01 M in ammonium citrate (apparent pH 7.0). The wipe solutions were analyzed by means of HPLC-MS/MS using a reversed-phase gradient system and electrospray ionization in positive ion mode with a triple-quadrupole MS detector. Accuracy and precision of this method were demonstrated by a series of recovery studies of both spiked solutions and extracted wipes from various surfaces (stainless steel, vinyl and Formica((r))) spiked with known levels of mitomycin C. Recoveries of spiked solutions containing the analyte demonstrate mean recoveries (accuracy) ranged from 93 to 105%. Precision as measured by the relative standard deviation (% RSD) of multiple samples (n= 10) at each concentration level demonstrated values of 7.5% or less. The recoveries from spiked surfaces varied from 30 to 99%. The limit of detection for this methodology is ~2 ng/100 cm(2) equivalent surface area, and the limit of quantitation is ~6 ng/100 cm(2). PMID- 25129063 TI - Discovery of common sequences absent in the human reference genome using pooled samples from next generation sequencing. AB - BACKGROUND: Sequences up to several megabases in length have been found to be present in individual genomes but absent in the human reference genome. These sequences may be common in populations, and their absence in the reference genome may indicate rare variants in the genomes of individuals who served as donors for the human genome project. As the reference genome is used in probe design for microarray technology and mapping short reads in next generation sequencing (NGS), this missing sequence could be a source of bias in functional genomic studies and variant analysis. One End Anchor (OEA) and/or orphan reads from paired-end sequencing have been used to identify novel sequences that are absent in reference genome. However, there is no study to investigate the distribution, evolution and functionality of those sequences in human populations. RESULTS: To systematically identify and study the missing common sequences (micSeqs), we extended the previous method by pooling OEA reads from large number of individuals and applying strict filtering methods to remove false sequences. The pipeline was applied to data from phase 1 of the 1000 Genomes Project. We identified 309 micSeqs that are present in at least 1% of the human population, but absent in the reference genome. We confirmed 76% of these 309 micSeqs by comparison to other primate genomes, individual human genomes, and gene expression data. Furthermore, we randomly selected fifteen micSeqs and confirmed their presence using PCR validation in 38 additional individuals. Functional analysis using published RNA-seq and ChIP-seq data showed that eleven micSeqs are highly expressed in human brain and three micSeqs contain transcription factor (TF) binding regions, suggesting they are functional elements. In addition, the identified micSeqs are absent in non-primates and show dynamic acquisition during primate evolution culminating with most micSeqs being present in Africans, suggesting some micSeqs may be important sources of human diversity. CONCLUSIONS: 76% of micSeqs were confirmed by a comparative genomics approach. Fourteen micSeqs are expressed in human brain or contain TF binding regions. Some micSeqs are primate-specific, conserved and may play a role in the evolution of primates. PMID- 25129064 TI - Usefulness and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (from the TRACER Trial). AB - The therapeutic potential of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (PCI) is unknown. This prespecified analysis of a postrandomization subgroup evaluated the effects of vorapaxar compared with placebo among Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) participants undergoing PCI, focusing on the implanted stent type (drug-eluting stent [DES] vs bare-metal stent [BMS]). Among 12,944 recruited patients, 7,479 (57.8%) underwent PCI during index hospitalization, and 3,060 (40.9%) of those patients received exclusively BMS, whereas 4,015 (53.7%) received DES. The median (twenty-fifth, seventy-fifth percentiles) duration of thienopyridine therapy was 133 days (47, 246) with BMS and 221 days (88, 341) with DES. At 2 years among patients undergoing PCI, the primary (cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) and secondary (cardiovascular death, myocardial infarction, or stroke) end points did not differ between vorapaxar and placebo groups, which was consistent with the treatment effect observed in the overall study population (p value for interaction = 0.540). However, the treatment effect trended greater (p value for interaction = 0.069) and the risk for bleeding in patients taking vorapaxar versus placebo appeared attenuated in BMS-only recipients. After adjustment for confounders, the interaction was no longer significant (p value = 0.301). The covariate that mostly explained the stent-type-by-treatment interaction was the duration of clopidogrel therapy. In conclusion, among patients with PCI, the effect of vorapaxar is consistent with the overall TRACER results. Patients who received a BMS underwent shorter courses of clopidogrel therapy and displayed trends toward greater ischemic benefit from vorapaxar and lesser bleeding risk, compared with patients who received a DES. PMID- 25129065 TI - Comparison of safety of sotalol versus amiodarone in patients with atrial fibrillation and coronary artery disease. AB - Sotalol is a commonly prescribed antiarrhythmic drug (AAD) used for maintaining sinus rhythm in patients with atrial fibrillation (AF). Although randomized studies have found that sotalol can significantly delay time to AF recurrence, its association with mortality is less clear, particularly among those with coronary artery disease. We examined outcomes of 2,838 patients with coronary artery disease and AF. Using Cox proportional hazards modeling, landmark analysis, and time-dependent covariates for drug therapy, we compared cumulative survival among patients treated with sotalol (n = 226), amiodarone (n = 856), or no AAD (n = 1,756). Median follow-up was 4.2 years (interquartile range [IQR] 2.0 7.4). The median age was 68 years (IQR 60-75). Compared with those treated with amiodarone or no AAD, patients treated with sotalol were less likely to be black (6% vs 13% vs 13%) and have a previous myocardial infarction (35% vs 51% vs 48%) or a left ventricular ejection fraction <40% (13% vs 26% vs 21%). In follow-up, persistence of sotalol was limited; 97% of patients treated with sotalol were treated for <25% of the follow-up period. In adjusted analysis accounting for time on therapy, sotalol use was associated with an increased risk of all-cause death compared with no drug (hazard ratio 1.53, 95% confidence interval 1.19 to 1.96, p = 0.0009), but a decreased risk of death compared with amiodarone (hazard ratio 0.72, 95% confidence interval 0.55 to 0.91, p = 0.0141). In conclusion, sotalol therapy was more frequently used in patients with fewer co-morbidities, often discontinued early in follow-up, and was associated with increased mortality compared with no AAD but decreased mortality relative to amiodarone. PMID- 25129066 TI - Effect of spironolactone on 30-day death and heart failure rehospitalization (from the COACH Study). AB - The aim of our study is to investigate the effect of spironolactone on 30-day outcomes in patients with acute heart failure (AHF) and the association between treatment and outcomes stratified by biomarkers. We conducted a secondary analysis of the biomarker substudy of the multicenter COACH (Co-ordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) trial involving 534 AHF patients for 30-day mortality and HF rehospitalizations. Spironolactone therapy was initiated and terminated at the discretion of the treating physician; 30-day outcomes were compared between patients who were treated with spironolactone and those who were not. Outcomes with spironolactone therapy were explored based on N-terminal pro-B-type natriuretic peptide, ST2, galectin-3, and creatinine levels. Spironolactone was prescribed to 297 (55.6%) patients at discharge (158 new and 139 continued). There were 19 deaths and 30 HF rehospitalizations among 46 patients by 30 days. Patients discharged on spironolactone had significantly less 30-day event (hazard ratio 0.538, p = 0.039) after adjustment for multiple risk factors. Initiation of spironolactone in patients who were not on spironolactone before admission was associated with a significant reduction in event rate (hazard ratio 0.362, p = 0.027). The survival benefit of spironolactone was more prominent in patient groups with elevations of creatinine, N-terminal pro-B-type natriuretic peptide, ST2, or galectin-3. In conclusion, AHF patients who received spironolactone during hospitalization had significantly fewer 30-day mortality and HF rehospitalizations, especially in high-risk patients. PMID- 25129067 TI - Prevalence, clinical correlates, and functional impact of subaortic ventricular septal bulge (from the Baltimore Longitudinal Study of Aging). AB - A localized hypertrophy of the subaortic segment of the ventricular septum ventricular septal bulge (VSB)-has been frequently described in series of elderly population, but its prevalence with age, clinical correlates, and impact on cardiac function and exercise capacity remain uncertain. We explored these associations in a cross-sectional sample without known cardiac disease from the Baltimore Longitudinal Study of Aging. We randomly selected 700 participants (50% men, mean age 64 +/- 15, range 26 to 95 years) and reviewed their echocardiograms. We identified 28 men and 21 women with VSB (7% overall prevalence). The prevalence of VSB significantly increased with age in both genders (p <0.0001). In multivariate logistic regression including hypertension and other cardiovascular risk factors, only age displayed a significant independent association with VSB (OR 1.06 per year, 95% confidence interval 1.03 to 1.10, p = 0.0001). After multiple adjustments, participants with VSB compared with those without had enhanced global left ventricular contractility (fractional shortening 41 +/- 1.3 vs 38 +/- 0.3%, p = 0.04; ejection fraction 71 +/- 1.6 vs 67 +/- 0.4%, p = 0.06; systolic velocity of the mitral annulus 8.4 +/- 0.1 vs 8.9 +/- 0.3, p = 0.06), and larger aortic root diameters (3.3 +/- 0.06 vs 3.1 +/- 0.02 cm, p = 0.02). In subgroup of participants who completed a maximal treadmill test (177 women and 196 men), those with VSB (19, 5.1%) had significantly lower peak oxygen consumption than their counterparts (19.6 +/- 3.8 vs 22.9 +/- 6.6 ml/kg/min, p = 0.03). However, this association was no longer significant after multiple adjustments. In conclusion, the presence of VSB is independently associated with older age and determines enhanced left ventricular contractility, without any evident impact on exercise capacity. PMID- 25129068 TI - Polysaccharopeptide enhanced the anti-cancer effect of gamma-tocotrienol through activation of AMPK. AB - BACKGROUND: Prostate cancer (PCa) frequently relapses after hormone ablation therapy. Unfortunately, once progressed to the castration resistant stage, the disease is regarded as incurable as prostate cancer cells are highly resistant to conventional chemotherapy. METHOD: We recently reported that the two natural compounds polysaccharopeptide (PSP) and Gamma-tocotrienols (gamma-T3) possessed potent anti-cancer activities through targeting of CSCs. In the present study, using both prostate cancer cell line and xenograft models, we seek to investigate the therapeutic potential of combining gamma-T3 and PSP in the treatment of prostate cancer. RESULT: We showed that in the presence of PSP, gamma-T3 treatment induce a drastic activation of AMP-activated protein kinase (AMPK). This was accompanied with inactivation of acetyl-CoA carboxylase (ACC), as evidenced by the increased phosphorylation levels at Ser 79. In addition, PSP treatment also sensitized cancer cells toward gamma-T3-induced cytotoxicity. Furthermore, we demonstrated for the first time that combination of PSP and gamma T3 treaments significantly reduced the growth of prostate tumor in vivo. CONCLUSION: Our results indicate that PSP and gamma-T3 treaments may have synergistic anti-cancer effect in vitro and in vivo, which warrants further investigation as a potential combination therapy for the treatment of cancer. PMID- 25129069 TI - Audit-identified avoidable factors in maternal and perinatal deaths in low resource settings: a systematic review. AB - BACKGROUND: Audits provide a rational framework for quality improvement by systematically assessing clinical practices against accepted standards with the aim to develop recommendations and interventions that target modifiable deficiencies in care. Most childbirth-associated mortality audits in developing countries are focused on a single facility and, up to now, the avoidable factors in maternal and perinatal deaths cataloged in these reports have not been pooled and analyzed. We sought to identity the most frequent avoidable factors in childbirth-related deaths globally through a systematic review of all published mortality audits in low and lower-middle income countries. METHODS: We performed a systematic review of published literature from 1965 to November 2011 in Pubmed, Embase, CINAHL, POPLINE, LILACS and African Index Medicus. Inclusion criteria were audits from low and lower-middle income countries that identified at least one avoidable factor in maternal or perinatal mortality. Each study included in the analysis was assigned a quality score using a previously published instrument. A meta-analysis was performed for each avoidable factor taking into account the sample sizes and quality score from each individual audit. The study was conducted and reported according to PRISMA guidelines for systematic reviews. RESULTS: Thirty-nine studies comprising 44 datasets and a total of 6,205 audited deaths met inclusion criteria. The analysis yielded 42 different avoidable factors, which fell into four categories: health worker-oriented factors, patient oriented factors, transport/referral factors, and administrative/supply factors. The top three factors by attributable deaths were substandard care by a health worker, patient delay, and deficiencies in blood transfusion capacity (accounting for 688, 665, and 634 deaths attributable, respectively). Health worker-oriented factors accounted for two-thirds of the avoidable factors identified. CONCLUSIONS: Audits provide insight into where systematic deficiencies in clinical care occur and can therefore provide crucial direction for the targeting of interventions to mitigate or eliminate health system failures. Given that the main causes of maternal and perinatal deaths are generally consistent across low resource settings, the specific avoidable factors identified in this review can help to inform the rational design of health systems with the aim of achieving continued progress towards Millennium Development Goals Four and Five. PMID- 25129070 TI - The relationship between the cranial base and jaw base in a Chinese population. AB - INTRODUCTION: The cranial base plays an important role in determining how the mandible and maxilla relate to each other. This study assessed the relationship between the cranial base and jaw base in a Chinese population. METHODS: This study involved 83 subjects (male: 27; female: 56; age: 18.4+/-4.2 SD years) from Hong Kong, who were classified into 3 sagittal discrepancy groups on the basis of their ANB angle. A cephalometric analysis of the angular and linear measurements of their cranial and jaw bases was carried out. The morphological characteristics of the cranial and jaw bases in the three groups were compared and assessments were made as to whether a relationship existed between the cranial base and the jaw base discrepancy. RESULTS: Significant differences were found in the cranial base angles of the three groups. Skeletal Class II cases presented with a larger NSBa, whereas skeletal Class III cases presented with a smaller NSBa (P<0.001). In the linear measurement, skeletal Class III cases presented with a shorter NBa than skeletal Class I and II cases (P<0.01). There was a correlation between the cranial base angle NSBa and the SNB for the whole sample, (r=-0.523, P<0.001). Furthermore, correlations between SBaFH and Wits (r=-0.594, P<0.001) and SBaFH and maxillary length (r=-0.616, P<0.001) were more obvious in the skeletal Class III cases. CONCLUSIONS: The cranial base appears to have a certain correlation with the jaw base relationship in a southern Chinese population. The correlation between cranial base and jaw base tends to be closer in skeletal Class III cases. PMID- 25129071 TI - Age-related change in sit-to-stand power in Japanese women aged 50 years or older. AB - BACKGROUND: This study examined whether the age-related change in power, calculated from the score of a sit-to-stand (STS) test, corresponds to those in knee extension torque and leg lean tissue mass in Japanese women aged 50 years or older. FINDINGS: Time for a 10-times-repeated STS test and knee extension torque were determined in 556 Japanese women aged 50 to 94 years. STS power was calculated using an equation reported previously. In addition, leg lean tissue mass was estimated using muscle thicknesses determined at thigh and lower leg. STS power, knee extension torque, and lean tissue mass were negatively correlated to age. STS power and knee extension torque, expressed as the percentages of the mean value of the corresponding variable for the subjects aged 50 to 54 years were lower than that of lean tissue mass in the subjects aged 60 years or over, and were similar in those aged under 75 years. However, the relative value of STS power was lower than that of knee extension torque in the subjects aged over 75 years. CONCLUSIONS: In Japanese women aged 50 to 74 years, STS power can be a convenient measure for assessing the age-related decline in knee extension torque, but not for leg lean tissue mass. At over 75 years old, the magnitude of the age-related decline in STS power does not parallel to that in the force generation capability of knee extensor muscles. PMID- 25129072 TI - Freezing and thawing of artificial ice by thermal switching of geometric frustration in magnetic flux lattices. AB - The problem of an ensemble of repulsive particles on a potential-energy landscape is common to many physical systems and has been studied in multiple artificial playgrounds. However, the latter usually involve fixed energy landscapes, thereby impeding in situ investigations of the particles' collective response to controlled changes in the landscape geometry. Here, we experimentally realize a system in which the geometry of the potential-energy landscape can be switched using temperature as the control knob. This realization is based on a high temperature superconductor in which we engineer a nanoscale spatial modulation of the superconducting condensate. Depending on the temperature, the flux quanta induced by an applied magnetic field see either a geometrically frustrated energy landscape that favours an ice-like flux ordering, or an unfrustrated landscape that yields a periodic flux distribution. This effect is reflected in a dramatic change in the superconductor's magneto-transport. The thermal switching of the energy landscape geometry opens new opportunities for the study of ordering and reorganization in repulsive particle manifolds. PMID- 25129073 TI - Biocomputing based on particle disassembly. AB - Nanoparticles with biocomputing capabilities could potentially be used to create sophisticated robotic devices with a variety of biomedical applications, including intelligent sensors and theranostic agents. DNA/RNA-based computing techniques have already been developed that can offer a complete set of Boolean logic functions and have been used, for example, to analyse cells and deliver molecular payloads. However, the computing potential of particle-based systems remains relatively unexplored. Here, we show that almost any type of nanoparticle or microparticle can be transformed into autonomous biocomputing structures that are capable of implementing a functionally complete set of Boolean logic gates (YES, NOT, AND and OR) and binding to a target as result of a computation. The logic-gating functionality is incorporated into self-assembled particle/biomolecule interfaces (demonstrated here with proteins) and the logic gating is achieved through input-induced disassembly of the structures. To illustrate the capabilities of the approach, we show that the structures can be used for logic-gated cell targeting and advanced immunoassays. PMID- 25129074 TI - Exposure to L-cycloserine incurs survival costs and behavioral alterations in Aedes aegypti females. AB - BACKGROUND: It was previously demonstrated that alanine aminotransferase (ALAT, EC 2.6.1.2) participates in maintaining the alanine-proline cycle between flight muscles and fat body during Aedes aegypti flight. ALAT is also actively involved in the metabolism of ammonia in A. aegypti. Here, we investigated the survival and behavioral costs of ALAT inhibition in A. aegypti females to better understand the role of ALAT in blood-fed mosquitoes. METHODS: We analyzed how A. aegypti female mosquitoes respond to blood meals supplemented with 0, 2.5, 5 and 10 mM L-cycloserine, a well-known inhibitor of ALAT in animals. Mosquitoes were also exposed to blood meals supplemented with L-cycloserine and different concentrations of glucose (0, 10 and 100 mM). Additionally, the effects of ALAT inhibitor and glucose in mosquitoes starved for 24 or 48 h were investigated. Survival and behavioral phenotypes were analyzed during a time course (1, 2, 4, 6, 12, 24, 48 and 72 h after feeding). RESULTS: L-cycloserine at 10 mM resulted in high mortality relative to control, with an acute effect during the first 6 h after treatment. A significant decrease in the number of active mosquitoes coinciding with an increase in futile wing fanning during the first 24 h was observed at all inhibitor concentrations. A high occurrence of knockdown phenotype was also recorded at this time for both 5 and 10 mM L-cycloserine. The supplementation of glucose in the blood meal amplified the effects of the ALAT inhibitor. In particular, we observed a higher mortality rate concomitant with an increase in the knockdown phenotype. Starvation prior to blood feeding also increased the effects of L-cycloserine with a rapid increase in mortality. CONCLUSIONS: Our results provide evidence that exposure of high doses of L cycloserine during A. aegypti blood feeding affects mosquito survival and motor activity, suggesting an interference with carbohydrate and ammonia metabolism in a time-dependent manner. PMID- 25129076 TI - Hippocampal-neocortical functional reorganization underlies children's cognitive development. AB - The importance of the hippocampal system for rapid learning and memory is well recognized, but its contributions to a cardinal feature of children's cognitive development-the transition from procedure-based to memory-based problem-solving strategies-are unknown. Here we show that the hippocampal system is pivotal to this strategic transition. Longitudinal functional magnetic resonance imaging (fMRI) in 7-9-year-old children revealed that the transition from use of counting to memory-based retrieval parallels increased hippocampal and decreased prefrontal-parietal engagement during arithmetic problem solving. Longitudinal improvements in retrieval-strategy use were predicted by increased hippocampal neocortical functional connectivity. Beyond childhood, retrieval-strategy use continued to improve through adolescence into adulthood and was associated with decreased activation but more stable interproblem representations in the hippocampus. Our findings provide insights into the dynamic role of the hippocampus in the maturation of memory-based problem solving and establish a critical link between hippocampal-neocortical reorganization and children's cognitive development. PMID- 25129075 TI - Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. AB - We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network. PMID- 25129079 TI - [NCCN Asian consensus statement - can Asian patients with cancer accept treatment modalities from NCCN guidelines ?]. AB - To spread the National Comprehensive Cancer Network(NCCN)guidelines widely in Asia, committee members from Asian countries have been preparing an Asia Consensus Statement(ACS)along the NCCN guidelines. The ACS for Kidney Cancer guidelines and Prostate Cancer guidelines were issued in 2009 and in 2011, respectively. In addition, second versions of both these guidelines were issued in 2011 and 2013, respectively. In this review, the process and contents of NCCN ACS have been described. PMID- 25129080 TI - [Overview of guidelines for proper use of the G-CSF(2013 edition)]. AB - Guidelines for proper use of the G-CSF(2001 edition)by the Japan Society of Clinical Oncology have been revised the first time in 12 years. The differences between the first edition and the new one are as follows: The new guidelines(2013 edition) adopted the clinical question format, and used the level of evidence and recommendation grades, along with the Handbook of Clinical Guidelines of Minds(2007 edition). There are relatively few evidence-based randomized controlled trials(RCTs) that can inform G-CSF use in Japan at present. Thus, we had to select the evidence from RCTs conducted in Europe and the USA when setting the recommendation level. Guidelines from Europe and the USA were also referred to; however, because the incidence of febrile neutropenia(FN)is presumed to differ between Japan and the USA/Europe, the clinical trials conducted in Japan were investigated as much as possible. New chapters on topics such as biosimilars, pegfilgrastim(domestic non-release), and the dosage and method of G CSF administration(medical insurance in Japan)were added. The chemotherapy regimen-specific incidence of FN in Japan for primary prophylactic G-CSF administration and G-CSF use in hematological malignancy were described in detail. Nurses, pharmacists, and medical doctors participated in guideline steering committee, because the new guidelines are directed at a wide range of health care workers. PMID- 25129078 TI - The GABAergic parafacial zone is a medullary slow wave sleep-promoting center. AB - Work in animals and humans has suggested the existence of a slow wave sleep (SWS) promoting/electroencephalogram (EEG)-synchronizing center in the mammalian lower brainstem. Although sleep-active GABAergic neurons in the medullary parafacial zone (PZ) are needed for normal SWS, it remains unclear whether these neurons can initiate and maintain SWS or EEG slow-wave activity (SWA) in behaving mice. We used genetically targeted activation and optogenetically based mapping to examine the downstream circuitry engaged by SWS-promoting PZ neurons, and we found that this circuit uniquely and potently initiated SWS and EEG SWA, regardless of the time of day. PZ neurons monosynaptically innervated and released synaptic GABA onto parabrachial neurons, which in turn projected to and released synaptic glutamate onto cortically projecting neurons of the magnocellular basal forebrain; thus, there is a circuit substrate through which GABAergic PZ neurons can potently trigger SWS and modulate the cortical EEG. PMID- 25129081 TI - [Primary and secondary prophylactic administration of granulocyte-colony stimulating factor(G-CSF)for febrile neutropenia]. AB - The Japanese guidelines for the proper use of granulocyte-colony stimulating factor(G-CSF)have been revised on the basis of the current international guidelines and latest evidence. The guidelines for primary and secondary prophylactic administration of G-CSF are clearly defined in the revised version. Primary prophylactic administration is recommended as per the incidence of febrile neutropenia(FN): it is highly recommended for patients with an FN rate>20%, but selectively recommended for patients with an FN rate<20%. Secondary prophylactic administration is recommended only for patients who should be maintained on a constant dose of G-CSF for curative purposes. The revised version aims to improve, not limit, the clinical use of G-CSF based on both patient- and evidence-oriented decisions in clinical practice. PMID- 25129082 TI - [Appropriate use of granulocyte colony-stimulating factor in the management of hematologic malignancies]. AB - There are two main types of therapy for hematologic malignancies: intensive cytotoxic chemotherapy and hematopoietic stem cell transplantation(HSCT). The roles of granulocyte colony-stimulating factor(G-CSF)in patients receiving HSCT are the mobilization of hematopoietic stem cells/progenitor cells into peripheral blood and the enhancement of neutrophil recovery as therapy or prophylaxis for fatal complications following HSCT. In the treatment of acute leukemias, G-CSF is used as therapy or prophylaxis for febrile complications during remission induction and post-remission therapies. In the treatment of lymphomas, primary prophylactic G-CSF is recommended during all cycles of chemotherapy when the expected incidence of neutropenic fever is more than 20% or when the patient is treated with potentially curative regimens. G-CSF is used as secondary prophylaxis to maintain dose intensity in patients with lymphomas treated in settings where reductions in chemotherapy dose intensity or dose density are associated with poorer prognosis. In the treatment of multiple myelomas, prophylactic G-CSF can be used when there is a high estimated risk of neutropenic fever(e. g., in patients receiving high-dose chemotherapy). For all cases, the appropriate use of G-CSF is recommended in accordance with the guidelines of the American Society of Clinical Oncology(ASCO), European Organisation for Research and Treatment of Cancer(EORTC), Infectious Diseases Society of America(IDSA), National Comprehensive Cancer Network(NCCN), and our JSCO-2013. PMID- 25129083 TI - [Use of granulocyte-colony stimulating factor(G-CSF)in patients with cancer at high risk of febrile neutropenia on the basis of high age and complications, recommendations for patients receiving radiotherapy, and adverse events because of G-CSF]. AB - Neutropenic complications are the primary dose-limiting toxic effects observed in patients treated with systemic cancer chemotherapy. Broad-spectrum antibiotic therapy should be promptly administered to patients with febrile neutropenia(FN). The risk assessment of FN includes the disease characteristics, chemotherapy regimen, individual patient risk factors, and treatment intent. After considering such risk factors of FN, clinicians should appropriately consider the use of granulocytecolony stimulating factor(G-CSF)as a prophylactic or therapeutic measure. Some types of lymphoma can be cured with chemotherapy. The incidence of FN in patients receiving the standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone(R-CHOP)regimen is approximately 20%. Primary prophylactic use of G-CSF is recommended for patients agedB 65 years having diffuse aggressive lymphoma and treated with curative chemotherapy in an effort to improve their quality of life(QOL). Primary prophylaxis is recommended for the prevention of FN in patients at high risk, on the basis of factors other than age. G-CSF should be avoided in patients receiving concomitant chemotherapy and radiation therapy, particularly in those with cancer involving the mediastinum. The adverse events of G-CSF are generally graded mild to moderate; however, rare life-threatening adverse effects have been published in the literature. A clinical practice guideline for the use of G-CSF was published by the Japan Society of Clinical Oncology in 2013. On the basis of this guideline, the above issues have been discussed in this paper. PMID- 25129077 TI - Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. AB - Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from four independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease. PMID- 25129084 TI - [Efficacy and safety of panitumumab for K-ras wild-type unresectable or recurrent colorectal cancer - a study focusing on first-line treatment]. AB - Panitumumab was approved in June 2010 for use in the treatment of unresectable advanced/recurrent colorectal cancer. Here, we report outcomes and adverse events of panitumumab combination therapy or single-agent chemotherapy for K-ras wild type unresectable or recurrent colorectal cancers. Our study focused on first line treatments. The study involved 18 patients who started receiving panitumumab in October 2010. Nine patients received panitumumab as a first-line treatment; 4, as a second-line treatment; and 5, as a third-line or subsequent treatment. The overall response rate was 27.8%. Among the patients who received panitumumab as a first-line treatment, the response rate was 55.6%. Grade 1 and 2 skin disorders were common adverse events. Grade 2 interstitial pneumonia was observed in 1 patient(5.6%). Grade 3 or higher events comprised peripheral neuropathy in 1 patient(5.6%)and neutropenia in another patient(5.6%). The treatment was beneficial, and metastatic foci were resected in 3 patients. In this study, the only adverse events of Grade 3 or higher were 1 case each of peripheral neuropathy and neutropenia. Accordingly, adequate control seemed possible. The specific line of treatment that panitumumab should belong to remains controversial. However, active initiation as first-line treatment should be considered for cases in which resection of metastatic foci can be expected from tumor reductions due to panitumumab. PMID- 25129085 TI - [Retrospective analysis of the bevacizumab and CapeOX combination in untreated metastatic/recurrent colorectal cancer]. AB - In recent years, there has been significant progress in systemic chemotherapy for metastatic or recurrent colorectal cancer. We investigated the clinical efficacy and feasibility of the bevacizumab and capecitabine /oxaliplatin(CapeOX)combination for untreated colorectal cancer. From October 2009 to June 2012, 38 patients were included, 18 receiving CapeOX alone and 20 receiving CapeOX plus bevacizumab. The response rate and disease-control rate were 16% and 5 0%, respectively, in the CapeOX arm, and 5 5% and 8 5%, respectively, in the CapeOX plus bevacizumab arm. Median progression-free survival was 8.0 months in the CapeOX arm and 1 2.8 months in CapeOX plus bevacizumab arm. The median overall survival was 21.6 months in the CapeOX arm and 3 4.0 months in CapeOX plus bevacizumab arm. Our results suggest that CapeOX treatment can be useful in the outpatient setting and more effective when combined with bevacizumab. Except in cases of bevacizumab intolerance, addition of bevacizumab to CapeOX treatment is considered useful as first-line therapy for metastatic or recur- rent colorectal cancer. PMID- 25129086 TI - [Tolerability of XELOX in postoperative adjuvant chemotherapy for colorectal cancer]. AB - A regimen of capecitabine plus oxaliplatin(XELOX)has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, few tolerability studies have been conducted in Japan. In this study, we retrospectively examined treatment continuation and the adverse events that occurred during 8 courses of postoperative adjuvant chemotherapy with XELOX in 21 patients with colorectal cancer who had undergone curative resection. The completion rate for 8 courses of treatment with XELOX was 71.4%, while the median relative dose intensities of capecitabine and oxaliplatin were 85.0% and 75.0%, respectively. Although the incidence of subsequent Grade 3 or higher hand-foot syndrome was 14.3%, the rate of peripheral neuropathy was 0%. Our hospital had a high rate of XELOX treatment continuation, suggesting that XELOX adjuvant chemotherapy would be well tolerated in clinical practice as well. PMID- 25129087 TI - [Evaluation of breath alcohol concentration after the administration of alcohol based docetaxel]. AB - In the present study, we measured breath alcohol concentration(BAC)after the administration of alcohol-containing docetaxel(OTX)in breast cancer patients, and examined the safety of OTX outpatient administration. Twenty breast cancer patients who received OTX chemotherapy at our outpatient facility were included. The administered doses were 100mg/m2 in 5 cases, 75mg/m / 2 in 13 cases, and 60 mg/m2 in 2 cases. BAC was measured 3 times: immediately after infusion, 30 minutes after infusion, and 60 minutes after infusion. No symptoms of hot flash or drunkenness due to alcohol were observed. BAC was detected in 10 cases(50%)immediately after infusion, in 7 cases(35%)at 30 minutes after infusion, and in 1 case(5%) at 60 minutes after infusion. BAC was more than 0.15mg/L in only 1 case(5%)and reduced to less than 0.15mg/L in all cases after 30 minutes. Our results suggest that the effects of alcohol are alleviated 60 minutes after infusion and that patients receiving OTX could return home safely. PMID- 25129088 TI - Seasonal variations in breast cancer diagnosis in Osaka, Japan. AB - To date, seasonal variations in breast cancer diagnosis have been reported in Western countries. In the present study, we calculated the number of breast cancer diagnoses according to season between 1976 and 2005, using data from the Osaka Cancer Registry. In all time periods and all age groups, breast cancer diagnosis showed peaks in early summer and troughs in winter. The number of breast cancer diagnoses in the spring, summer, autumn, and winter were 2,595(26%), 2,739(27%), 2,585(26%), and 2,120(21%)in 1976-1985; 4,219(26%), 4,581(28%), 4,2 62(26%), and 3,466(21%)in 1986-1995; and 6,299(25%), 6,852(28%), 6,368(26%), and 5,335(22%)in 1996-2005, respectively. Most cases were diagnosed because of an awareness of a breast mass. The trend in screening-detected cases differed from the overall trend. As screening becomes more widely adopted, these seasonal variations might change. Careful monitoring is needed to confirm these findings. PMID- 25129089 TI - [A case of recurrent lung cancer with bone metastases treated with tegafur-uracil and zoledronic acid for long-term survival]. AB - We present the case of an 84-year-old man with lumbago due to bone metastases from lung cancer that recurred three years after surgery. The patient received carboplatin-paclitaxel combination as first-line chemotherapy for the treatment of lung cancer, and palliative radiotherapy for the treatment of bone metastases. Gemcitabine was administered as second-line chemotherapy. However, disease progression was observed after three years, and he developed pulmonary metastases. The general condition of the patient worsened, and tegafur-uracil chemotherapy was initiated. Zoledronic acid was also administered. The tegafur uracil treatment resulted in the disappearance of pulmonary metastases, and a stabilization of the bone metastases. Disease progression was observed after 6 years with a recurrence of pulmonary metastases; however, this did not have a negative impact on the patient's quality of life. Although slow progression may be inherent to lung cancers, it is also possible that the tegafur-uracil and zoledronic acid combination might have contributed to the patient's improved performance. PMID- 25129090 TI - [Analysis of factors associated with the quality of life in patients with non small cell lung cancer who received outpatient pemetrexed maintenance therapy]. AB - Increasing number of patients with advanced non-small cell lung cancer are receiving outpatient maintenance chemotherapy. It is very important to maintain these patients' quality of life(QOL). Pemetrexed has been reported to be an effective maintenance chemotherapy. However, its effects on the QOL of patients with non-small cell lung cancer who are undergoing outpatient maintenance chemotherapy are unknown; therefore, we conducted this study. To investigate factors that influence the QOL of these patients, we provided a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs(QOL-ACD)"to 7 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores, as well as other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale", were analyzed. No significant reductions in any of the factors were observed in this study. PMID- 25129091 TI - [Neuroendocrine gallbladder cancer treated with cisplatin plus irinotecan - a case report]. AB - A 52-year-old woman was referred to our hospital because of upper abdominal pain. A computed tomography(CT)scan revealed bulky gallbladder and liver tumors. We reached a tentative diagnosis of invasive adenocarcinoma of the gallbladder and performed needle biopsy of the tumor. Biopsied specimens showed the proliferation of small round to oval cells with scanty cytoplasm and high rates of mitosis. Immunohistochemical examination showed that many tumor cells were positive for chromogranin A, synaptophysin, and CD56. Our final diagnosis was neuroendocrine carcinoma of the gallbladder with multiple liver metastases. The patient received cisplatin plus irinotecan chemotherapy. Remarkable shrinkage was observed after 3 cycles of chemotherapy, and a good response continued for more than 6 months. Gallbladder cancer patients generally have a poor response to chemotherapy, so we should be aware of the histopathological diagnosis of the cancer before starting treatment. PMID- 25129092 TI - [A patient with advanced breast cancer who developed bacterial meningitis after chemotherapy]. AB - A 76-year-old woman was admitted to our hospital because of a right breast tumor and a skin ulcer. The patient was diagnosed as having advanced breast cancer T4bN2M1(lung), Stage IV. A regimen of 5-fluorouracil(500mg/m2)with epirubicin(100mg/m / 2)and cyclophosphamide(500mg/m2)(FEC100)was administered. However, the patient was hospitalized 12 days later because of febrile neutropenia. The patient experienced a stiff neck the next day, and bacterial meningitis was diagnosed on the basis of cerebrospinal fluid examination. Antibacterial agents were administered according to the clinical practice guidelines of bacterial meningitis. The patient recovered and was discharged from our hospital 24 days after admission. Bacterial meningitis after chemotherapy is rare, but this could be progress to a serious condition. Early diagnosis and treatment are paramount in such cases. PMID- 25129093 TI - [A case of a patient with gastric cancer and peritoneal dissemination who survived for more than 10 years after successful treatment with S-1]. AB - A 50-year-old female patient underwent distal gastrectomy and intraperitoneal CDDP administration for advanced gastric cancer accompanied by severe peritoneal dissemination. She valued her quality of life and chose an oral anticancer drug, S-1, as a postoperative chemotherapy agent. S-1 was administered at a dose of 100mg/body/day for 4 weeks, followed by a 2- week rest. There were no adverse events due to S-1 and no exacerbation of peritoneal dissemination in the 5 years following surgery. The S-1 administration schedule was then changed to alternate day administration. Eight years after the surgery, the patient discontinued S-1 treatment and has since survived for 11 years with no obvious cancer recurrence. PMID- 25129094 TI - [A case of pathologically complete response in a patient with locally advanced sigmoid colon cancer after chemotherapy including bevacizumab/FOLFOX4]. AB - A 65-year-old man complaining of abdominal pain was admitted to our hospital. A diagnosis of colon ileus due to sigmoidal colon cancer was made. A stoma was created at the transverse colon, and elective surgery was scheduled. During the operation, the tumor was found to have invaded the bladder and the pelvic wall, making curative resection impossible. Chemotherapy consisting of bevacizumab/oxaliplatin, Leucovorin, and 5-fluorouracil(FOLFOX4, intravenous drip infusion every 2 weeks)was started. After 12 courses of treatment, remarkable shrinkage of the tumor was noted, which led us to perform a sigmoidectomy and partial resection of the bladder wall. A histopathological study of the surgically resected specimen showed no cancer cells. Recovery was uneventful and the patient was discharged on the 17th postoperative day. In cases of advanced colon cancer, complete response of the primary tumor with preoperative chemotherapy is very unusual. We conclude that chemotherapy with bevacizumab/FOLFOX4 plays a role in the management of advanced/unresectable colon cancer. PMID- 25129095 TI - [Effectiveness of azacitidine in chronic myelomonocytic leukemia harboring del(20q) - a case report]. AB - A 7 1-year-old man was admitted to our hospital with leukocytosis and anemia. Chronic myelomonocytic leukemia (CMML)harboring del(20q)was diagnosed by peripheral blood examination and bone marrow aspiration. The patient was subsequently treated with azacitidine, which resulted in rapid disappearance of monocytosis and resolved his dependency on red cell transfusion. With regard to the chromosomal abnormality, although del(20q)is estimated to be encountered in approximately 0.7-1.0% of all CMML cases, its significance in prognosis has not been fully analyzed. Hence, more such cases need to be evaluated to elucidate the therapeutic outcome of CMML involving del(20q). In addition, the Wilms tumor-1(WT 1)level in the patient gradually decreased after the initiation of azacitidine therapy. This phenomenon of WT1 decrease synchronizing with the patient's clinical improvement might reflect therapeutic efficacy with regard to the clinical course, as had been observed in acute myeloid leukemia and myelodysplastic syndrome. PMID- 25129096 TI - [A case of small intestinal cancer in the upper intestine after pylorus preserving pancreaticoduodenectomy]. AB - We report a case of small intestinal cancer that arose in the upper intestine 16 years after pylorus-preserving pancreaticoduodenectomy( PPPD). An 84-year-old man, who had undergone PPPD for benign biliary tract disease 16 years previously, was found to have a primary small intestinal tumor in the upper intestine by upper gastrointestinal endoscopy, and primary intestinal cancer in the upper intestine was finally diagnosed. We performed partial resection of the upper small intestine and stomach and partial colectomy of the transverse colon to account for direct invasion. Histopathologically, the primary lesion was diagnosed as a moderately to poorly differentiated adenocarcinoma. Small intestinal cancer in the upper intestine after PPPD is extremely rare. PMID- 25129097 TI - [A case report of primary adenocarcinoma of the small intestine with peritoneal dissemination treated with multidisciplinary therapy]. AB - A 55-year-old woman consulted our hospital complaining of abdominal distention and vomiting. She was diagnosed with a malignant tumor in the small intestine and an ovarian tumor with an upper gastro-intestinal series based on a computerized tomography(CT)examination. Intra-operative findings showed that the primary tumor was located in the proximal jejunum, 10 cm on the anal side from Treitz's ligament. There were no liver metastases, but the tumor had spread into the peritoneal cavity(light ovary). The jejunum and light ovary were therefore resected. Pathological diagnosis of the resected specimen revealed adenocarcinoma with lymph node metastases(T4N1M1, UICC StageIV). The patient received systemic chemotherapy with oral S-1. A recurrent lesion on the right ovary was detected 6 months after surgery. The patient subsequently underwent resection of the right ovary. For lung metastases and recurrent peritoneal dissemination, combination chemotherapy with XELOX or FOLFIRI, along with capecitabine plus bevacizumab, and cetuximab, was administered. The patient died 33 months after the first surgery. Primary small intestinal adenocarcinoma is a rare disease, and it is often diagnosed at an advanced stage because there are very few characteristic symptoms. This case may be an important case for the development of a standard chemotherapy regimen for advanced and recurrent adenocarcinoma of the small intestine. PMID- 25129098 TI - Neurolysis for secondary sciatic nerve entrapment: evaluation of surgical feasibility and functional outcome. AB - BACKGROUND: The study included 11 patients; seven males and four females with mean age of 68.3 +/-11 years. All patients had sciatic nerve entrapment: three had a penetrating injury, three suffered postoperative trauma, two had a crush injury, two had inadvertent injections and one was trapped in a machine belt. Clinical examination included: an evaluation of the extent of motor and sensory impacts according to the British Medical Research Council (BMRC) scale and the Semmes-Weinstein monofilament test; assessment of pain sensation using the visual analogue scale (VAS); electromyography; and nerve conduction velocitiey determination. The applied operative procedure for sciatic neurolysis was modulated according to the suspected site of sciatic nerve entrapment. At 6 and 12 months after surgery all patients were evaluated for recovery of motor and sensory function. RESULTS: All patients passed the smooth intraoperative course within a mean operative time of 77.7 +/-21 min. The mean duration of wound drainage and postoperative hospital stay was 2.6 +/-0.7 and 4.8 +/-0.8 days, respectively. Pain sensation showed progressive significant improvement in nine patients but decreased at time of discharge and remained stationary till 12-m post-operative (PO). Recovery of motor function showed progressive significant improvement at 6 and 12 months after sciatic nerve neurolysis. The frequency of patients having muscle power recovery and regained sensation was significantly higher at 6-m and 12-m PO as compared to preoperative grading with a significantly higher frequency at the 6-m grading compared to preoperative grading. Two patients showed no change of their muscle strength grade, while nine patients showed improvement for a total success rate of motor strength recovery of 81.8%. At 6- m PO five patients showed no change of their sensory group, while six patients showed improvement for a total success rate of sensation recovery of 54.5%. At 12-m PO ten patients had fullly recovered protective sensation for a success rate of 90.9%. CONCLUSION: Surgical exploration and neurolysis of cases with sciatic nerve entrapment is a safe and effective therapeutic modality with significant improvement of both motor and sensory functions without risk of additional deficit secondary to neurolysis. PMID- 25129099 TI - Quercetin glycosides induced neuroprotection by changes in the gene expression in a cellular model of Parkinson's disease. AB - Quercetin glycosides, rutin and isoquercitrin, are potent antioxidants that have been found to possess neuroprotective effect in diseases like Parkinson's and Alzheimer's disease. In the present study, we have examined the gene expression changes with rutin and isoquercitrin pretreatment on 6-hydroxydopamine (6-OHDA) treated toxicity in rat pheochromocytoma (PC12) cells. PC12 cells were pretreated with rutin or isoquercitrin and subsequently exposed to 6-OHDA. Rutin-pretreated PC12 attenuated the Park2, Park5, Park7, Casp3, and Casp7 genes which were expressed significantly in the 6-OHDA-treated PC12 cells. Rutin upregulated the TH gene which is important in dopamine biosynthesis, but isoquercitrin pretreatment did not affect the expression of this gene. Both rutin and isoquercitrin pretreatments upregulated the ion transport and antiapoptotic genes (NSF and Opa1). The qPCR array data were further validated by qRT-PCR using four primers, Park5, Park7, Casp3, and TH. This finding suggests that changes in the expression levels of transcripts encoded by genes that participate in ubiquitin pathway and dopamine biosynthesis may be involved in Parkinson's disease. PMID- 25129100 TI - Microvascular lesions by estrogen-induced ID3: its implications in cerebral and cardiorenal vascular disease. AB - Severe symptoms of cerebral and cardiorenal vascular diseases can be triggered when cerebral, coronary, or glomerular arterioles grow inappropriately as a result of abnormal cell proliferation. The risk factor(s) and molecular mechanisms responsible for microvascular lesion formation are largely unknown. Although controversial, both animal and epidemiological studies have shown that estrogen increases the risk of stroke which may be due to microvascular lesions. Since microvascular diseases are characterized by excessive vessel growth, it is plausible that estrogen-induced neovascularization contributes to the growth of microvascular lesions. We present evidence for how ID3 overexpression in endothelial cells contributes to the development of an estrogen-induced neovascular phenotype with an additional focus on Pyk2 kinase. Our data showed that ID3 overexpression increased neovascularization, cell migration, and spheroid growth of human cerebral microvascular endothelial cells, hCMEC/D3. ID3 overexpressing cells showed significant estrogen-induced G2/M phase transition. Estrogen treatment increased both ID3 phosphorylation; total protein that was inhibited by tamoxifen, and Pyk2-mediated estrogen-induced ID3 mRNA expression. These findings suggest that Pyk2 signals ID3 expression and ID3 is necessary for estrogen-induced neovascularization in hCMEC/D3 cells. A better understanding of how microvascular lesions depend on ID3 may open new avenues for prevention and treatment of neurological diseases. PMID- 25129101 TI - Qualitative and Quantitative Assessment of Hepatitis A Virus in Wastewaters in Tunisia. AB - Hepatitis A causes substantial morbidity in both industrialized and non industrialized countries and represents an important health problem in several southern Mediterranean countries. The objectives of the study were as follows: (a) to assess the occurrence of hepatitis A virus (HAV) in Tunisia through the monitoring of urban wastewaters collected at wastewater treatment plants (WTPs); (b) to characterize environmental strains; and (c) to estimate the viral load in raw and treated sewages, in order to evaluate the potential impact on superficial waters receiving discharges. A total of 150 raw and treated wastewaters were collected from three WTPs and analyzed by both qualitative (RT-PCR/nested) and quantitative (qRT-PCR) methods. Of these, 100 (66%) were found to be positive for HAV by the qualitative assay: 68.3% in influents and 64.7% in effluents. The vast majority of HAV sequences belonged to sub-genotype IA, with 11 different strains detected found to be identical to clinical strains isolated from Tunisian patients with acute hepatitis. Five unique variants were also detected, not previously reported in clinical cases. Only two IB strains were found, confirming the rarity of this sub-genotype in this country. The results of the present study indicate a wide circulation of the pathogen in the population, most probably in the form of asymptomatic infections, a finding consistent with the classification of the country as having intermediate/high endemicity. Quantitative data showed high viral loads in influents (3.5E+05 genome copies/liter, mean value) as well as effluents (2.5E+05 genome copies/liter, mean value), suggesting that contaminated water could be a critical element in transmission. PMID- 25129102 TI - Antiviral Effects of Lactococcus lactis on Feline Calicivirus, A Human Norovirus Surrogate. AB - Foodborne viruses, particularly human norovirus (NV) and hepatitis virus type A, are a cause of concern for public health making it necessary to explore novel and effective techniques for prevention of foodborne viral contamination, especially in minimally processed and ready-to-eat foods. This study aimed to determine the antiviral activity of a probiotic lactic acid bacterium (LAB) against feline calicivirus (FCV), a surrogate of human NV. Bacterial growth medium filtrate (BGMF) of Lactococcus lactis subsp. lactis LM0230 and its bacterial cell suspension (BCS) were evaluated separately for their antiviral activity against FCV grown in Crandell-Reese feline kidney (CRFK) cells. No significant antiviral effect was seen when CRFK cells were pre-treated with either BGMF (raw or pH 7 adjusted BGMF) or BCS. However, pre-treatment of FCV with BGMF and BCS resulted in a reduction in virus titers of 1.3 log10 tissue culture infectious dose (TCID)50 and 1.8 log10 TCID50, respectively. The highest reductions in FCV infectivity were obtained when CRFK cells were co-treated with FCV and pH 7 adjusted BGMF or with FCV and BCS (7.5 log10 TCID50 and 6.0 log10 TCID50, respectively). These preliminary results are encouraging and indicate the need for continued studies on the role of probiotics and LAB on inactivation of viruses in various types of foods. PMID- 25129103 TI - Tachykinin Peptide, substance p, and its receptor have a significant role in tissue reactions induced by cytotoxic therapy. PMID- 25129105 TI - Does endoscopic assessment of mucosal healing affect IBD management? PMID- 25129104 TI - The transcription factor FOXA2 suppresses gastric tumorigenesis in vitro and in vivo. AB - BACKGROUND AND AIMS: The transcription factor forkhead box A2 (FOXA2) plays a central role in the development of endoderm-derived organs. It has been reported that FOXA2 acts as a suppressor in many kinds of tumor. However, little is known about the role of FOXA2 in gastric cancer. METHODS: The expression of FOXA2 in gastric cancer tissue samples from 89 patients was assessed by immunohistochemistry, and the clinicopathological characteristics of the samples were analyzed. The human gastric cancer cell line, BGC-823, was used to investigate the effects of FOXA2 in gastric cancer in vitro and in vivo and the potential mechanism involved was explored. RESULTS: FOXA2 expression in human gastric cancer cell lines and human gastric cancer tissues was lower compared with the normal gastric epithelium cell line GES1 and normal adult gastric tissues, respectively. Patients with high FOXA2 expression level had longer 5 year overall survival than those with low FOXA2 expression level. FOXA2 markedly inhibited growth of BGC-823 cells accompanied with the cell cycle arrest and apoptosis. Infection of BGC-823 cells by FOXA2 lentivirus resulted in reduced cell tumorigenesis in vitro and in vivo. Moreover, expression of Mucin 5AC was up regulated along with increased expression of exogenous FOXA2 in BGC-823 cells; in contrast, dedifferentiation markers, BMI, CD54 and CD24, were down-regulated. CONCLUSIONS: These results suggest that FOXA2 induces the differentiation of gastric cancer and highlight FOXA2 as a novel therapeutic target and prognostic marker for human gastric cancer. PMID- 25129106 TI - Proton receptor GPR68 expression in dendritic-cell-like S100beta-positive cells of rat anterior pituitary gland: GPR68 induces interleukin-6 gene expression in extracellular acidification. AB - S100beta-positive cells, which do not express the classical pituitary hormones, appear to possess multifunctional properties and are assumed to be heterogeneous in the anterior pituitary gland. The presence of several protein markers has shown that S100beta-positive cells are composed of populations such as stem/progenitor cells, epithelial cells, astrocytes and dendritic cells. Recently, we succeeded in separating S100beta-positive cells into round-cell (dendritic-cell-like) and process-cell types. We also found the characteristic expression of anti-inflammatory factors (interleukin-6, Il-6) and membrane receptors (integrin beta-6) in the round type. Here, we further investigate the function of the subpopulation of S100beta-positive cells. Since IL-6 is also a paracrine factor that regulates hormone producing-cells, we examine whether a correlation exists among extracellular acid stress, IL-6 and hormone production by using primary cultures of anterior pituitary cells. Dendritic-cell-like S100beta-positive cells notably expressed Gpr68 (proton receptor) and Il-6. Furthermore, the expression of Il-6 and proopiomelanocortin (Pomc) was up regulated by extracellular acidification. The functional role of IL-6 and GPR68 in the gene expression of Pomc during extracellular acidification was also examined. Small interfering RNA for Il-6 up-regulated Pomc expression and that for Gpr68 reversed the down-regulation of Il-6 and up-regulated Pomc expression by extracellular acidification. Thus, S100beta-positive dendritic-like cells can sense an increase in extracellular protons via GPR68 and respond by the production of IL-6 in order to suppress the up-regulation of Pomc expression. PMID- 25129107 TI - Involvement of RhoA/ROCK in insulin secretion of pancreatic beta-cells in 3D culture. AB - Cell-cell contacts and interactions between pancreatic beta-cells and/or other cell populations within islets are essential for cell survival, insulin secretion, and functional synchronization. Three-dimensional (3D) culture systems supply the ideal microenvironment for islet-like cluster formation and functional maintenance. However, the underlying mechanisms remain unclear. In this study, mouse insulinoma 6 (MIN6) cells were cultured in a rotating 3D culture system to form islet-like aggregates. Glucose-stimulated insulin secretion (GSIS) and the RhoA/ROCK pathway were investigated. In the 3D-cultured MIN6 cells, more endocrine-specific genes were up-regulated, and GSIS was increased to a greater extent than in cells grown in monolayers. RhoA/ROCK inactivation led to F-actin remodeling in the MIN6 cell aggregates and greater insulin exocytosis. The gap junction protein, connexin 36 (Cx36), was up-regulated in MIN6 cell aggregates and RhoA/ROCK-inactivated monolayer cells. GSIS dramatically decreased when Cx36 was knocked down by short interfering RNA and could not be reversed by RhoA/ROCK inactivation. Thus, the RhoA/ROCK signaling pathway is involved in insulin release through the up-regulation of Cx36 expression in 3D-cultured MIN6 cells. PMID- 25129108 TI - A new role of Klumpfuss in establishing cell fate during the GMC asymmetric cell division. AB - Studies in the Drosophila embryonic NB4-2 lineage have suggested that the transcription factor Klumpfuss (Klu) functions within embryonic neuroblast lineages to differentiate between the identities of two adjacent ganglion mother cells (GMCs). However, because of the limited lineage markers available, these observations have been made only for the NB4-2 lineage. Recent findings have placed this transcription factor in the vanguard of Drosophila neural stem cell biology by demonstrating that Klu is necessary for larval neuroblast growth and self-renewal. Here, we have studied the role of klu in an incipient model in order to address basic mechanisms of neural specification: the Va system. None of the previously reported roles of Klu satisfactorily explain our observations. Unexpectedly, in this lineage, klu is necessary for differentiating between the fates of the two neurons born from a unique GMC; klu mutants produce two B-type cells, rather than one B-type (Notch-OFF) and one A-type (Notch-ON) cell. Additionally, our results demonstrate that Klu operates in the GMC and/or in the newly born neuron, but not in the neuroblast. Unlike in larval neuroblasts in which Klu is an executor of Notch signaling, we have found that Klu does not lie downstream of the Notch pathway in this cell division context. PMID- 25129109 TI - Xenogeneic transplantation of articular chondrocytes into full-thickness articular cartilage defects in minipigs: fate of cells and the role of macrophages. AB - Xenogeneic or allogeneic chondrocytes hold great potential to build up new cartilage in vivo. However, immune rejection is a major concern for the utility of universal donor-derived cells. In order to verify the reported immune privilege of chondrocytes in vivo, the aim of this study was to assess engraftment of human articular chondrocytes (HAC) in minipig knee cartilage defects and their contribution to cartilage regeneration. HAC were transplanted matrix-assisted within two hydrogels into full-thickness cartilage defects of minipigs or implanted ectopically into immune deficient mice to assess redifferentiation capacity. At 2 and 4 weeks after surgery, cell-persistence and host cell invasion were monitored by species-specific in situ hybridization and RT-PCR. Early tissue regeneration was evaluated by histomorphometry and a modified O'Driscoll score. HAC capable of successful in vivo chondrogenic redifferentiation persisted at ectopic sites for 4 weeks in both carrier materials. Early defect regeneration involved extensive host cell invasion and a decline of HAC to less than 5 % of initial cell numbers in 6/12 defects within 2 weeks. Few clusters of persisting HAC within collagen type II-rich tissue were surrounded by porcine macrophages. Four weeks after cell transplantation, most of the defects contained well-integrated cell-rich tissue free of human cells with no apparent difference between hydrogel carriers. In summary, HAC failed to engraft in porcine articular cartilage defects despite their ability for successful in vivo redifferentiation. The co-localization of macrophages to hydrogel-implanted HAC suggests active graft rejection without evidence for an immune-privileged status of xenogeneic chondrocytes in a large animal joint. PMID- 25129110 TI - Changing healthcare capital-to-labor ratios: evidence and implications for bending the cost curve in Canada and beyond. AB - Healthcare capital-to-labor ratios are examined for the 10 provincial single payer health care plans across Canada. The data show an increasing trend particularly during the period 1997-2009 during which the ratio as much as doubled from 3 to 6 %. Multivariate analyses indicate that every percentage point uptick in the rate of increase in this ratio is associated with an uptick in the rate of increase of real per capita provincial government healthcare expenditures by approximately $31 ([Formula: see text] 0.01). While the magnitude of this relationship is not large, it is still substantial enough to warrant notice: every percentage point decrease in the upward trend of the capital-to-labor ratio might be associated with a one percentage point decrease in the upward trend of per capita government healthcare expenditures. An uptick since 1997 in the rate of increase in per capita prescription drug expenditures is also associated with a decline in the trend of increasing per capita healthcare costs. While there has been some recent evidence of a slowing in the rate of health care expenditure increase, it is still unclear whether this reflects just a pause, after which the rate of increase will return to its baseline level, or a long-term shift; therefore, it is important to continue to explore various policy avenues to affect the rate of change going forward. PMID- 25129111 TI - Drug compartmentalization as strategy to improve the physico-chemical properties of diclofenac sodium loaded niosomes for topical applications. AB - The objective of this research was to study the effect of diclofenac sodium compartmentalization on the physico-chemical properties (such as size, drug entrapment efficiency and percutaneous permeation across rabbit skin) of niosomal vesicles used as carriers. Niosomes were prepared starting from nonionic commercial surfactants belonging to the class of Polysorbates and Pluronics: mixtures of Span 60/F127 and Tween 60/F127 at different ratios were used to obtain vesicles and all formulations were compared in terms of dimensions, morphology, polydispersity index and entrapment efficiency. Moreover, the enhancing effect of niosomes on the ex vivo percutaneous penetration of diclofenac sodium was investigated using Franz-type diffusion chambers and compared to that obtained by using the corresponding drug solution. Results demonstrated that niosomes were spherical and homogeneous in shape. Their size was found to be dependent on the hydrophile-lipophile balance of the surfactant mixture: increasing hydrophobicity resulted in smaller vesicles. Drug incorporation led to a significant variation in vesicle size dependently from the compartment in which the drug was located. The permeation of diclofenac from free solution used as control was found to be lower respect to that obtained for all niosomal formulations, that can be considered as percutaneous permeation enhancers. In particular, the results indicated that the highest cumulative amounts of diclofenac permeated across rabbit skin after 24 h were obtained by formulations in which the drug was located in the aqueous core. PMID- 25129112 TI - A micro-drive hearing aid: a novel non-invasive hearing prosthesis actuator. AB - The direct hearing device (DHD) is a new auditory prosthesis that combines conventional hearing aid and middle ear implant technologies into a single device. The DHD is located deep in the ear canal and recreates sounds with mechanical movements of the tympanic membrane. A critical component of the DHD is the microactuator, which must be capable of moving the tympanic membrane at frequencies and magnitudes appropriate for normal hearing, with little distortion. The DHD actuator reported here utilized a voice coil actuator design and was 3.7 mm in diameter. The device has a smoothly varying frequency response and produces a precisely controllable force. The total harmonic distortion between 425 Hz and 10 kHz is below 0.5 % and acoustic noise generation is minimal. The device was tested as a tympanic membrane driver on cadaveric temporal bones where the device was coupled to the umbo of the tympanic membrane. The DHD successfully recreated ossicular chain movements across the frequencies of human hearing while demonstrating controllable magnitude. Moreover, the micro actuator was validated in a short-term human clinical performance study where sound matching and complex audio waveforms were evaluated by a healthy subject. PMID- 25129113 TI - Shape and size of the medial patellofemoral ligament for the best surgical reconstruction: a human cadaveric study. AB - PURPOSE: The aim of this study was to investigate the shape and the attachments of the medial patellofemoral ligament (MPFL) in cadaver specimens to determine an anatomical basis for the best MPFL reconstruction. METHODS: Twenty fresh-frozen knees were used. Dissection protocol implied performing dissections from within the knee joint. We investigated the shape and the attachments between the MPFL and the quadriceps tendon, the patellar and femur insertions, and all the other relationships with the medial soft tissues of the knee. RESULTS: The distal fibers of MPFL were interdigitated with the deep layer of the medial retinaculum. All isolated ligament had a sail-like shape with the patellar side bigger than the femoral side. The femoral insertion, distinct both from medial epicondyle and adductor tubercle, was located at 9.5 mm (range 4-22) distal and anterior respect to adductor tubercle and proximal and posterior to epicondyle. The medial third of the thickness of patella was involved in the insertion. The proximal third of the patella is always involved in the MPFL attachment; in 45% of the cases, it was extended to the medial third and in one case, an extension at the distal third was found. Additionally in 35% (7 cases), it extended to the quadriceps tendon and it were inconstantly attached at the vastus medialis obliques (VMO) tendon and at the vastus intermedius (VI) tendon in an aponeurotic structure. CONCLUSIONS: The MPFL is a distinct structure that goes from patella to femur with a sail-like shape; its patellar insertion, that mostly occur via an aponeurosis tissue with VMO and VI, is at the proximal third of the patella but it may extend in some cases to the medial third patella or to the quadriceps tendon, or very rarely to the distal third of the patella. In the femoral side, the MPFL is inserted in its own site, in most cases distinct both from epicondyle and adductor tubercle, located on average at a 9.5 mm distance distally and anteriorly in respect to the adductor tubercle. Its lower margin was difficult to define. Given the importance of this structure, it must be reconstructed as anatomically as possible in its insertion and in its shape. Many attempts have been made to make functional reconstructions with less than excellent results. PMID- 25129114 TI - Cutaneous manifestations of infection in returning travelers. AB - Dermatologic problems are common in returning travelers who seek medical care. Some common illnesses such as cellulitis or abscesses occur in travelers but are not unique to this patient group. Additionally, dermatologic illnesses not due to infection such as drug eruptions or phototoxicity are seen. Skin manifestations occur in many tropical illnesses such as dengue, schistosomiasis, and leishmaniasis. This article reviews the common causes of cutaneous illnesses associated with travel including non-infectious causes, infections that are not limited to travelers, and infections that are almost exclusively seen in travelers. PMID- 25129115 TI - Microbiology and treatment of cerebrospinal fluid shunt infections in children. AB - Infections of cerebrospinal fluid (CSF) shunts remain a common surgical complication causing significant morbidity in children with hydrocephalus. As most of the literature regarding these infections includes only small cohorts from a single institution's experience, there remain large knowledge gaps and little support for the prevailing management strategies. Regarding the microbiology of shunt infections, little has changed in the past 10 years, other than the emergence of methicillin-resistant strains of coagulase-negative staphylococcus (CoNS) and Staphylococcus aureus, which remain the two predominant etiologic agents. Molecular diagnostics such as multiplex PCR have been used to identify the complex microflora of shunt infections and in the future could prove a useful adjunct for early diagnosis and targeting of antimicrobial therapy. Antibiotic-impregnated catheters for use in external ventricular drains and CSF shunts have been adopted into clinical practice and appear to reduce the risk of shunt infection by susceptible organisms. PMID- 25129116 TI - Management of Intra-abdominal Infections due to Carbapenemase-Producing Organisms. AB - The prevalence of bacterial resistance to carbapenem antibiotics continues to increase because of bacteria producing metallo-beta-lactamases (MBL), called carbapenemase-producing organisms (CPO). Enterobacteriaceae, which can be a common cause of intra-abdominal infections (IAIs), have become carbapenem resistant Enterobacteriaceae (CRE). Updated international guidelines for the treatment of both IAIs and IAIs due to CRE have been published. Given the multifaceted nature of these infections, these recommendations have been jointly reviewed and endorsed by the Surgical Society and the Association of Medical Microbiology and Infectious Disease. The aims of this review are to summarize the general and new generation of multimodal procedure to manage IAIs due to CRE and review the data available on the combination of interventions to reduce CRE. Future research should focus on the development of novel and safe antimicrobial therapies and the quantification of the incremental effect of infection control programmes and new methods to rapidly detect pathogens before patients enter the surgical setting. PMID- 25129117 TI - Ventilator-associated conditions versus ventilator-associated pneumonia: different by design. AB - The Centers for Disease Control and Prevention (CDC) released a new surveillance concept called ventilator-associated conditions (VACs) in early 2013. VAC was created to overcome some of the limitations of traditional ventilator-associated pneumonia (VAP) definitions, including their complexity, subjectivity, and insensitivity to complications other than pneumonia. VAC is defined by sustained increases in ventilator support after >=2 days of stable or decreasing settings. The VAC definition was designed to be objective, reproducible, and amenable to automated analysis. Moreover, VAC purposefully broadens the scope of surveillance to include physiologically significant complications of care in addition to pneumonia, most commonly pulmonary edema, atelectasis, and acute respiratory distress syndrome. VAC definitions offer an opportunity for hospital quality improvement programs to get a fuller picture of the breadth and burden of complications in their critically ill populations and to use these data to catalyze enhanced prevention and control programs to better prevent these conditions. PMID- 25129118 TI - [Pulmonary arterial hypertension associated with connective tissue diseases]. AB - Pulmonary arterial hypertension (PAH) is a classical complication of connective tissue diseases (CTD), particularly in systemic sclerosis (SSc), systemic lupus erythematous (SLE) or mixed connective tissue diseases (MCTD). The prevalence of PAH in SSc, as measured by right heart catheterization (RHC), is estimated between 7.85 to 13%. The detection of PAH in SSc is based on trans-thoracic echocardiography. Early detection in pulmonary hypertension is the best way to improve the survival in these diseases. In the DETECT study, 19% of high-risk PAH patients with SSc (SSc diagnosed less than 3 years before and DLco<60% predicted) have PAH as measured by RHC. Specific treatments for PAH are less efficient in PAH related to SSc than in idiopathic PAH. The main characteristic of PAH related to CTD other than SSc is a good response to immunosuppressive treatment, with an improvement in 50% of cases in SLE or MCTD. The prognosis of PAH associated with CTD seem to improve with the diversification of treatments available, but remains reserved. Therapeutic combinations and new molecules should allow to improve the prognosis. PMID- 25129119 TI - Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning--an ultrahigh-field MR pilot study. AB - OBJECTIVE: To investigate posterior visual pathway damage in multiple sclerosis using ultrahigh-field magnetic resonance imaging (MRI) at 7 Tesla (7 T), and to determine its correlation with visual disability and retinal fibre layer (RNFL) damage detectable by optic coherence tomography (OCT). METHODS: We studied 7 T MRI, OCT, functional acuity contrast testing (FACT), and visually evoked potentials (VEP, n = 16) in 30 patients (including 26 relapsing-remitting MS and four clinically isolated syndrome patients) and 12 healthy controls to quantify RNFL thickness, optic radiation lesion volume, and optic radiation thickness. RESULTS: Optic radiation lesion volume was associated with thinning of the optic radiation (p < 0.001), delayed VEP (p = 0.031), and visual disability indicated by FACT (p = 0.020). Furthermore, we observed an inverse correlation between optic radiation lesion volume and RNFL thickness (p < 0.001), including patients without previous optic neuritis (p < 0.001). CONCLUSIONS: Anterior visual pathway damage, but also (subclinical) optic radiation integrity loss detectable by 7 T MRI are common findings in MS that are mutually affected. Given the association between optic radiation damage, visual impairment, and increased VEP latency in this exploratory study of a limited sample size, clinicians should be aware of acute lesions within the optic radiation in patients with (bilateral) visual disturbances. KEY POINTS: * Focal destruction of the optic radiation is detectable by 7 T MRI. * Focal optic radiation damage is common in MS. * Optic radiation damage is associated with RNFL thinning, detectable by OCT. * Optic radiation damage is associated with delayed VEP and visual dysfunction. * RNFL thickness in non-optic neuritis eyes correlates with optic radiation demyelination. PMID- 25129121 TI - Sorptive capacity of membrane lipids, storage lipids, and proteins: a preliminary study of partitioning of organochlorines in lean fish from a PCB-contaminated freshwater lake. AB - Knowledge on the internal distribution of halogenated organic chemicals (HOCs) would improve our understanding of dose-effect relationships and subsequently improve risk assessment of contaminated sites. Herein, we determine the concentrations of HOCs based on equilibrium partitioning in storage lipids, membrane lipids, and proteins in field-contaminated fish using equilibrium sampling devices. The study shows the importance of protein as a sorptive phase in lean fish. Our results provide a basis for using species-specific equilibrium partitioning coefficients between sorptive tissues and fish internal water as a substitute for K(ow) in, for example, upgrading models that simulate food-chain accumulation of the chemical. PMID- 25129120 TI - Short- and long-term outcomes of LigaSure versus conventional surgery for curative gastric cancer resection: a matched pair analysis. AB - BACKGROUND: The LigaSure vessel sealing system allows dissection and hemostasis in a safe and quick way, and it has been reported to be an effective tool to shorten operative time and reduce intraoperative blood loss for various surgeries. However, short- and long-term outcomes in comparison with conventional surgery for gastric cancer resection are limited. METHODS: Between January 2005 and December 2009, 121 patients underwent curative resection for gastric cancer with LigaSure. Perioperative and long-term results were compared with those of 242 matched patients who received curative resection for gastric cancer with the conventional technique. Immediate operation outcomes, operation morbidity, recurrence and survival were compared between groups. RESULTS: In the LigaSure group compared with the conventional group, operation time was 156 versus 183 min (P < 0.0001), intraoperative blood loss was 181 versus 236 ml (P = 0.042), intraoperative blood transfusion was 68 versus 161 ml (P = 0.014), and hospital stay was 11.9 versus 13.6 days (P = 0.001). There were no differences in operation morbidity, recurrence rates, overall and disease-free survival between the LigaSure and conventional groups. CONCLUSIONS: LigaSure is associated with shorter operation time and hospital stay, less blood loss and transfusion, and comparable operation morbidity and long-term outcomes in comparison with conventional surgery for curative gastric cancer resection. PMID- 25129122 TI - Role of thromboelastography and rapid thromboelastography to assess the pharmacodynamic effects of vitamin K antagonists. AB - Thromboelastography (TEG) measures the effects of antithrombotic agents by assessing global functional clotting status by evaluating the viscoelastic properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses tissue factor in addition to standard kaolin to accelerate activation of the clotting cascade, has been proposed to obtain more immediate results. The correlation between results of TEG or r-TEG with international normalized ratio (INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and represents the aim of this study. Patients on chronic therapy with VKAs (n = 100) were included in an observational prospective pharmacodynamic study. The correlation between TEG parameters, in particular markers of thrombus generation [Reaction time (R), maximum rate of thrombus generation (MRTG), and time to maximum rate of thrombus generation (TMRTG)], and INR values as well as the concordance between these parameters and therapeutic INR ranges were evaluated. In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG parameters with TEG parameters and INR values was also assessed. No correlation was found between INR and TEG parameters of thrombus generation, in particular between INR and R (r = 0.189, p = 0.06), MRTG (r = -0.027, p = 0.79), and TMRTG (r = 0.188, p = 0.06). Further, no concordance was found between these parameters and recommended INR ranges. Significant Spearman correlations were found between INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p = 0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p = 0.617). Results were obtained in 24 +/- 6 versus 12 +/- 4 min with TEG and r-TEG, respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful tool to evaluate VKA anticoagulant effect, compared with standard INR measurements. However, r-TEG parameters of thrombus generation correlate with INR levels, suggesting a possible role of this assay for measuring more expeditiously anticoagulant treatment effects. PMID- 25129123 TI - A role for membrane shape and information processing in cardiac physiology. AB - While the heart is a dynamic organ and one of its major functions is to provide the organism with sufficient blood supply, the regulatory feedback systems, which allow adaptation to hemodynamic changes, remain not well understood. Our current description of mechanosensation focuses on stretch-sensitive ion channels, cytoskeletal components, structures such as the sarcomeric Z-disc, costameres, caveolae, or the concept of tensegrity, but these models appear incomplete as the remarkable plasticity of the myocardium in response to biomechanical stress and heart rate variations remains unexplained. Signaling activity at membranes depends on their geometric parameters such as surface area and curvature, which links shape to information processing. In the heart, continuous cycles of contraction and relaxation reshape membrane morphology and hence affect cardio mechanic signaling. This article provides a brief review on current models of mechanosensation and focuses on how signaling, cardiac myocyte dynamics, and membrane shape interact and potentially give rise to a self-organized system that uses shape to sense the extra- and intracellular environment. This novel concept may help to explain how changes in frequency, and thus membrane shape, affect cardiac plasticity. One of the conclusions is that hypertrophy and associated fibrosis, which have been considered as necessary to cope with increased wall stress, can also be seen as part of complex feedback systems which use local membrane inhomogeneity in different cardiac cell types to influence whole organphysiology and which are predicted to fine-tune and thus regulate membrane mediated signaling. PMID- 25129124 TI - Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats. AB - Dipeptidyl-peptidase IV (DPP-IV) is an enzyme responsible for the metabolism of endogenous gut-derived hormone, glucagon-like peptide-1 (GLP-1). DPP-IV is known for its role in energy homeostasis and pharmacological blockade of this enzyme is a recently approved clinical strategy for the management of type II diabetes. Accumulating evidences suggest that enzyme DPP-IV can affect spectrum of central nervous system (CNS) functions. However, little is known about the role of this enzyme in ethanol-mediated neurobehavioral complications. The objective of the present study was to examine the impact of DPP-IV inhibitor, sitagliptin on the development of tolerance to anxiolytic effect of ethanol and anxiety associated with ethanol withdrawal in rats. A dose-response study revealed that sitaglitpin (20 mg/kg, p.o.) per se exhibit anxiolytic effect in the elevated plus maze (EPM) test in rats. Tolerance to anxiolytic effect of ethanol (2 g/kg, i.p.; 8 % w/v) was observed from 7(th) day of ethanol-diet (6 % v/v) consumption. In contrast, tolerance to anxiolytic effect of ethanol was delayed in rats that were treated daily with sitagliptin (20 mg/kg, p.o.) as tolerance was observed from 13(th)day since commencement of ethanol-diet consumption. Discontinuation of rats from ethanol-diet after 15-days of ethanol consumption resulted in withdrawal anxiety between 8 h and 12 h post-abstinence. However, rats on 15-day ethanol-diet with concomitant sitagliptin (20 mg/kg, p.o.) treatment exhibited delay in appearance (24 h post-withdrawal) of withdrawal anxiety. In summary, DPP-IV inhibitors may prove as an attractive research strategy against ethanol tolerance and dependence. PMID- 25129125 TI - CD44 expression in curettage and postoperative specimens of endometrial cancer. AB - BACKGROUND: Adhesive molecules like CD44 are well defined key players in the metastatic cascade in many cancers, including endometrial cancer. They could play a role of markers of invasion, metastasis and prognostic factors. AIM OF THE STUDY: The aim of the study is to assess a possible role of the CD44 as a marker of invasion in endometrial cancer, both at the moment of preoperative workup and final staging. MATERIALS AND METHODS: Available for analysis were archival specimens of 51 patients who had underwent curettage and surgery between 2002 and 2007. An immunohistochemical study for CD44 expression was performed in curettage and postoperative specimens. Normal endometrium of 20 randomly chosen patients was used as a control group. RESULTS: In endometrial cancer the expression of CD44 was significantly more intensive than in normal endometrium. In postoperative specimens, the CD44 expression was weaker in serous than in endometrioid cancer. There was no significant correlation between the adhesion molecule expression and clinicopathological features: grade,depth of invasion, cervical involvement, serosal and adnexal involvement, lymph-vascular space involvement, lymph node and distant metastases nor FIGO stage. CONCLUSIONS: An increased expression of CD44 in endometrial cancer suggests its possible role in pathogenesis of this disease, however, it doesn't seem to be crucial. Different expression of the CD44 in endometrioid and papillary-serous type may reflect different pathogenesis of these types of cancer. No statistically proved relation between the investigated molecule expression and clinicopathological parameters suggests scepticism about its use in diagnostic process of endometrial cancer. PMID- 25129126 TI - Regional variation in breast cancer treatment in the Netherlands and the role of external peer review: a cohort study comprising 63,516 women. AB - BACKGROUND: Treatment variation is an important issue in health care provision. An external peer review programme for multidisciplinary cancer care was introduced in 1994 in the Netherlands to improve the multidisciplinary organisation of cancer care in hospitals.So far the clinical impact of external quality assessment programmes such as external peer review and accreditation remains unclear. Our objective was to examine the degree of variation in treatment patterns and the possible effect of external peer review for multidisciplinary cancer care for breast cancer patients. METHODS: Patients with breast cancer were included from 23 hospitals from two 'intervention regions' with the longest experience with the programme and 7 hospitals that never participated (control group). Data on tumour and treatment characteristics were retrieved from the Netherlands Cancer Registry. Treatment modalities investigated were: the completeness of breast conserving therapy, introduction of the sentinel node biopsy, radiotherapy after breast conserving surgery for ductal carcinoma in situ (DCIS), adjuvant radiotherapy for locally advanced breast cancer (T3/M0 or any T,N2-3/M0), adjuvant chemotherapy for early stage breast cancer (T1-2/N+/M0) and neo-adjuvant chemotherapy for T4/M0 breast cancer. Hospitals from the two intervention regions were dichotomised based on their implementation proportion (IP) of recommendations from the final reports of each peer review (high IP vs. low IP). This was regarded as a measure of how well a hospital participated in the programme. RESULTS: 63,516 female breast cancer patients were included (1990 2010). Variation in treatment patterns was observed between the intervention regions and control group. Multidisciplinary treatment patterns were not consistently better for patients from hospitals with a high IP. CONCLUSIONS: There is no relationship between the external peer review programme for multidisciplinary cancer care and multidisciplinary treatment patterns for breast cancer patients. Regional factors seem to exert a stronger effect on treatment patterns than hospital participation in external peer review. PMID- 25129127 TI - Utility of an initial adaptive bladder volume control with ultrasonography for proton-beam irradiation for prostate cancer. AB - PURPOSE: Our purpose was to evaluate the utility of time-fixed bladder volume control and adaptive bladder volume control with ultrasonography (US). MATERIALS AND METHODS: Seventy-five patients with prostate cancer treated with proton-beam therapy were enrolled. Treatment plans were created using computed tomography (CT) images obtained 60 min after urination with usual water intake. Just before each irradiation, bladder volume was measured with US at the directed urine collection time. Bladder volume was calculated according to orthogonal diameters. A bladder volume of <50 ml was considered to reflect a collapsed bladder. The percentage of collapsed bladders was examined in total and from the first to fifth irradiations. RESULTS: In total, 1,439 US confirmations (51 %) in 2,821 fractions were obtained and analyzed. A collapsed bladder was observed 152 of 1,439 times (11 %) in total, and the percentages of collapsed bladders from the first to fifth irradiations were 32 %, 18 %, 16 %, 12 %, and 7 %, respectively. CONCLUSION: Time-fixed bladder control is associated with a risk of bladder volume insufficiency. Adaptive bladder volume control with initial US feedback could decrease the risk of bladder volume insufficiency. PMID- 25129128 TI - High-density genetic linkage map construction and identification of fruit-related QTLs in pear using SNP and SSR markers. AB - Pear (Pyrus spp) is an important fruit crop, grown in all temperate regions of the world, with global production ranked after grape and apples among deciduous tree crops. A high-density linkage map is a valuable tool for fine mapping quantitative trait loci (QTL) and map-based gene cloning. In this study, we firstly constructed a high-density linkage map of pear using SNPs integrated with SSRs, developed by the rapid and robust technology of restriction-associated DNA sequencing (RADseq). The linkage map consists of 3143 SNP markers and 98 SSRs, 3241 markers in total, spanning 2243.4 cM, with an average marker distance of 0.70 cM. Anchoring SSRs were able to anchor seventeen linkage groups to their corresponding chromosomes. Based on this high-density integrated pear linkage map and two years of fruit phenotyping, a total of 32 potential QTLs for 11 traits, including length of pedicel (LFP), single fruit weight (SFW), soluble solid content (SSC), transverse diameter (TD), vertical diameter (VD), calyx status (CS), flesh colour (FC), juice content (JC), number of seeds (NS), skin colour (SC), and skin smooth (SS), were identified and positioned on the genetic map. Among them, some important fruit-related traits have for the first time been identified, such as calyx status, length of pedicel, and flesh colour, and reliable localization of QTLs were verified repeatable. This high-density linkage map of pear is a worthy reference for mapping important fruit traits, QTL identification, and comparison and combination of different genetic maps. PMID- 25129130 TI - A network perspective on nitrogen metabolism from model to crop plants using integrated 'omics' approaches. AB - Nitrogen (N), as an essential element in amino acids, nucleotides, and proteins, is a key factor in plant growth and development. Omics approaches such as metabolomics and transcriptomics have become a promising way to inspect complex network interactions in N metabolism and can be used for monitoring the uptake and regulation, translocation, and remobilization of N. In this review, the authors highlight recent progress in omics approaches, including transcript profiling using microarrays and deep sequencing, and show recent technical developments in metabolite profiling for N studies. Further, network analysis studies including network inference methods with correlations, information theoretic measures, and a network concept to examine gene expression clusters in relation to N regulatory systems in plants are introduced, and integrating network inference methods and integrated networks using multiple omics data are discussed. Finally, this review summarizes recent omics application examples using metabolite and/or transcript profiling analysis to elucidate the regulation of N metabolism and signalling and the coordination of N and carbon metabolism in model plants (Arabidopsis and rice), crops (tomato, maize, and legumes), and trees (Populus). PMID- 25129129 TI - SRR1 is essential to repress flowering in non-inductive conditions in Arabidopsis thaliana. AB - Timing of flowering is determined by environmental and developmental signals, leading to promotion or repression of key floral integrators. SENSITIVITY TO RED LIGHT REDUCED (SRR1) is a pioneer protein previously shown to be involved in regulation of the circadian clock and phytochrome B signalling in Arabidopsis thaliana. This report has examined the role of SRR1 in flowering time control. Loss-of-function srr1-1 plants flowered very early compared with the wild type under short-day conditions and had a weak flowering response to increasing daylength. Furthermore, FLOWERING LOCUS T (FT) transcript levels were elevated already in short days in srr1-1 compared with the wild type. This correlated with elevated end of day levels of CONSTANS (CO), whereas levels of CYCLING DOF FACTOR 1 (CDF1), a repressor of CO transcription, were reduced. srr1-1 gi-2 and srr1-1 co-9 double mutants showed that SRR1 can also repress flowering independently of the photoperiodic pathway. srr1-1 flowered consistently early between 16 degrees C and 27 degrees C, showing that SRR1 prevents premature flowering over a wide temperature range. SRR1 also promotes expression of the repressors TEMPRANILLO 1 (TEM1) and TEM2. Consequently their targets in the gibberellin biosynthesis pathway were elevated in srr1-1. SRR1 is thus an important focal point of both photoperiodic and photoperiod-independent regulation of flowering. By stimulating expression of the FT-binding repressors CDF1, TEM1 and TEM2, and FLC, flowering is inhibited in non-inductive conditions. PMID- 25129132 TI - Nitrogen control of developmental phase transitions in Arabidopsis thaliana. AB - Nitrogen (N) is an essential macronutrient and a key structural component of macromolecules in plants. N nutrients and metabolites can act as signals that impact on many aspects of plant biology. The plant life cycle involves a series of developmental phase transitions that must be tightly coordinated to external and internal cues in order to ensure plant survival and reproduction. N availability is one of the factors controlling phase changes. In this review, we integrate and summarize the known effects of N over different developmental stages in plants. Substantial advances have been made in our understanding of signalling and N-responsive gene regulatory networks. We focus on the molecular mechanisms underlying N regulation of developmental transitions and the role of putative new regulators that might link N availability to pathways controlling Arabidopsis growth and development from seed germination through the plant reproductive transition. PMID- 25129131 TI - Insights into transcriptional regulation of beta-D-N-acetylhexosaminidase, an N glycan-processing enzyme involved in ripening-associated fruit softening. AB - Tomato (Solanum lycopersicum) fruit ripening-specific N-glycan processing enzyme, beta-D-N-acetylhexosaminidase (beta-Hex), plays an important role in the ripening associated fruit-softening process. However, the regulation of fruit ripening specific expression of beta-Hex is not well understood. We have identified and functionally characterized the fruit ripening-specific promoter of beta-Hex and provided insights into its transcriptional regulation during fruit ripening. Our results demonstrate that RIPENING INHIBITOR (RIN), a global fruit ripening regulator, and ABSCISIC ACID STRESS RIPENING 1 (SlASR1), a poorly characterized ripening-related protein, are the transcriptional regulators of beta-Hex. Both RIN and SlASR1 directly bound to the beta-Hex promoter fragments containing CArG and C2-3(C/G)A cis-acting elements, the binding sites for RIN and SlASR1, respectively. Moreover, beta-Hex expression/promoter activity in tomato fruits was downregulated once expression of either RIN or SlASR1 was suppressed; indicating that RIN and SlASR1 positively regulate the transcription of beta-Hex during fruit ripening. Interestingly, RIN could also bind to the SlASR1 promoter, which contains several CArG cis-acting elements, and SlASR1 expression was suppressed in rin mutant fruits, indicating that RIN also acts as a positive regulator of SlASR1 expression during fruit ripening. Taken together, these results suggest that RIN, both directly and indirectly, through SlASR1, regulates the transcription of beta-Hex during fruit ripening. The fruit ripening-specific promoter of beta-Hex could be a useful tool in regulating gene expression during fruit ripening. PMID- 25129134 TI - The development of differences in hospital costs accross income groups in Finland from 1998 to 2010. AB - OBJECTIVE: To quantify differences in hospital costs between socioeconomic groups and the development over time. METHODS: Register data on somatic specialised hospital admissions for patients aged between 25 and 84 in Finland in 1998-2010 were used with income data individually linked to them. The cost of an admission was calculated by multiplying the number of a patient's inpatient days by the inpatient day cost of the patient's DRG. We calculated age-standardised admission costs per resident and per user as well as costs per inpatient day and concentration indices separately for men and women. RESULTS: Hospital admission costs reduced with increasing income. The difference between the extreme income quintiles was more than 50% throughout the study period, and this difference widened. However, the cost per inpatient day was more than 20% higher in the highest income group. The differences between income groups were the most prominent in disease categories involving surgery. CONCLUSIONS: The growth between socioeconomic groups in hospital costs is presumably mainly due to increasing differences in morbidity. More attention needs to be paid to prevention of health inequalities and access to and content of primary care among low-income groups in order to decrease the need for hospitalisations. PMID- 25129135 TI - Perspectives of physicians practicing in low and middle income countries towards generic medicines: a narrative review. AB - OBJECTIVES: This review was conducted to document published literature related to physicians' knowledge, attitudes, and perceptions of generic medicines in low- and middle-income countries (LMICs) and to compare the findings with high-income countries. METHODS: A systematic search of articles published in peer-reviewed journals from January 2001 to February 2013 was performed. The search comprised nine electronic databases. The search strategy involved using Boolean operators for combinations of the following terms: generic medicines, generic medications, generic drugs, generic, generic substitution, generic prescribing, international non-proprietary, prescribers, doctors, general practitioners, physicians, and specialists. RESULTS: Sixteen articles were included in this review. The majority (n=11) were from high income countries and five from LMICs. The main difference between high income countries and LMICs is that physicians from high income countries generally have positive views whereas those from LMICs tend to have mixed views regarding generic medicines. Few similarities were identified among different country income groups namely low level of physicians' knowledge of the basis of bioequivalence testing, cost of generic medicines as an encouraging factor for generic medicine prescribing, physicians' concerns towards safety and quality of generic medicines and effect of pharmaceutical sales representative on generic medicine prescribing. CONCLUSION: The present literature review revealed that physicians from LMICs tend to have mixed views regarding generic medicines. This may be due to differences in the health care system and pharmaceutical funding system, medicine policies, the level of educational interventions, and drug information sources in countries of different income levels. PMID- 25129133 TI - Small RNAs as important regulators for the hybrid vigour of super-hybrid rice. AB - Heterosis is an important biological phenomenon; however, the role of small RNA (sRNA) in heterosis of hybrid rice remains poorly described. Here, we performed sRNA profiling of F1 super-hybrid rice LYP9 and its parents using high-throughput sequencing technology, and identified 355 distinct mature microRNAs and trans acting small interfering RNAs, 69 of which were differentially expressed sRNAs (DES) between the hybrid and the mid-parental value. Among these, 34 DES were predicted to target 176 transcripts, of which 112 encoded 94 transcription factors. Further analysis showed that 67.6% of DES expression levels were negatively correlated with their target mRNAs either in flag leaves or panicles. The target genes of DES were significantly enriched in some important biological processes, including the auxin signalling pathway, in which existed a regulatory network mediated by DES and their targets, closely associated with plant growth and development. Overall, 20.8% of DES and their target genes were significantly enriched in quantitative trait loci of small intervals related to important rice agronomic traits including growth vigour, grain yield, and plant architecture, suggesting that the interaction between sRNAs and their targets contributes to the heterotic phenotypes of hybrid rice. Our findings revealed that sRNAs might play important roles in hybrid vigour of super-hybrid rice by regulating their target genes, especially in controlling the auxin signalling pathway. The above finding provides a novel insight into the molecular mechanism of heterosis. PMID- 25129136 TI - Sodium pentaborate pentahydrate and pluronic containing hydrogel increases cutaneous wound healing in vitro and in vivo. AB - After a disruption of skin integrity, the body produces an immediate response followed by a functional and comparable regeneration period, referred to as wound healing. Although normal wounds do not need much attention during the healing period, chronic (non-healing) wounds are the major challenge of current dermatological applications. Therefore, developing new, safe, and effective wound healing drugs has always been an attractive area of international research. In the current study, sodium pentaborate pentahydrate (NaB), pluronics (Plu; F68 and F127), and their combinations were investigated for their wound healing activities, using in vitro and in vivo approaches. The results revealed that NaB significantly increased migration capacity and superoxide dismutase activity in primary human fibroblasts. Combinations of optimized concentrations for pluronic block co-polymers further increased cell migration, and the messenger RNA (mRNA) expression levels of important growth factor and cytokines (vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta), and tumor necrosis factor alpha (TNF-alpha)). NaB containing hydrogel co-formulated with pluronics was also investigated for their wound healing activities using a full thickness wound model in rats. Macroscopic and histopathological analysis confirmed that wounds in combination gel-treated groups healed faster than those of control groups. NaB/Plu gel application was found to increase wound contraction and collagen deposition in the wound area. Therefore, our results suggest that NaB, and its pluronics combination, could be used in dermatological clinics and be a future solution for chronic wounds. However, further studies should be conducted to explore its exact action of mechanism and effects of this formulation on chronic wounds. PMID- 25129137 TI - Selenium deficiency inhibits the conversion of thyroidal thyroxine (T4) to triiodothyronine (T3) in chicken thyroids. AB - Selenium (Se) influences the metabolism of thyroid hormones in mammals. However, the role of Se deficiency in the regulation of thyroid hormones in chickens is not well known. In the present study, we examined the levels of thyroidal triiodothyronine (T3), thyroidal thyroxine (T4), free triiodothyronine, free thyroxine (FT4), and thyroid-stimulating hormone in the serum and the mRNA expression levels of 25 selenoproteins in chicken thyroids. Then, principal component analysis (PCA) was performed to analyze the relationships between the selenoproteins. The results indicated that Se deficiency influenced the conversion of T4 to T3 and induced the accumulation of T4 and FT4. In addition, the mRNA expression levels of the selenoproteins were generally decreased by Se deficiency. The PCA showed that eight selenoproteins (deiodinase 1 (Dio1), Dio2, Dio3, thioredoxin reductase 2 (Txnrd2), selenoprotein i (Seli), selenoprotein u (Selu), glutathione peroxidase 1 (Gpx1), and Gpx2) have similar trends, which indicated that they may play similar roles in the metabolism of thyroid hormones. The results showed that Se deficiency inhibited the conversion of T4 to T3 and decreased the levels of the crucial metabolic enzymes of the thyroid hormones, Dio1, Dio2, and Dio3, in chickens. In addition, the decreased selenoproteins (Dio1, Dio2, Dio3, Txnrd2, Seli, Selu, Gpx1, and Gpx2) induced by Se deficiency may indirectly limit the conversion of T4 to T3 in chicken thyroids. The information presented in this study is helpful to understand the role of Se in the thyroid function of chickens. PMID- 25129138 TI - Just like a circus: the public consumption of sex differences. AB - The study of sex differences is a rich, productive area of neuroscience, yielding findings that inform our understanding of basic biology and hold promise for clinical applications. There is a tremendous, problematic mismatch, however, between the actual implications of this research and what has generally been communicated to the public. The message communicated by the media, popular press, and in some cases researchers is often inaccurate with respect to what can and cannot be concluded from the data. This misrepresentation of findings has led to a crisis in public education and threatens to do the same in public health. Here, I suggest a number of ways that neuroscientists might address this growing problem. First, we should acknowledge that the term 'sex difference' is usually interpreted by the media and the public as evidence for dichotomous categories that do not actually exist. Because data rarely sort so cleanly into sex-specific categories, clearer presentation of the nature and size of sex differences is warranted. The term 'sex effect' may be preferable to 'sex difference' when the effect is not large. Second, factors that covary with sex, particularly experience, should be considered as causes of sex differences before the idea of "hardwiring" is invoked. Finally, we should be more vigilant about how our own findings are conveyed to policymakers and the public and speak out when they are misrepresented. PMID- 25129139 TI - Physiological correlates of psychopathy, antisocial personality disorder, habitual aggression, and violence. AB - This chapter reviews the existing literature on physiological correlates of psychopathy, antisocial personality disorder, and persistent violence/aggression. Coverage is provided of findings from studies utilizing peripheral, electrocortical, and neuroimaging measures. The review begins with a discussion of how psychopathy and antisocial personality are defined, and how these conditions relate to one another and to violent behavior. A case is made that the relationships psychopathy and ASPD show with violent and aggressive behavior, and similarities and differences in associations of each with physiological measures of various types can be understood in terms of symptomatic features these conditions have in common versus features that distinguish them. Following this, an overview is provided of major lines of evidence emerging from psychophysiological and neuroimaging studies conducted to date on these conditions. The final section of the chapter summarizes what has been learned from these existing studies and discusses implications and directions for future research. PMID- 25129140 TI - Connectivity measurements for network imaging. AB - Communication across the brain networks is dependent on neuronal oscillations. Detection of the synchronous activation of neurons can be used to determine the well-being of the connectivity in the human brain networks. Well-connected highly synchronous activity can be measured by MEG, EEG, fMRI, and PET and then analyzed with several types of mathematical algorithms. Coherence is one mathematical method that can detect how well 2 or more sensors or brain regions have similar oscillatory activity with each other. Phase synchrony can be used to determine if these oscillatory activities are in sync or out of sync with each other. Correlation is used to determine the strength of interaction between two locations or signals. Granger causality can be used to determine the direction of the information flow in the neuronal brain networks. Statistical analysis can be performed on the connectivity results to verify evidence of normal or abnormal network activity in a patient. PMID- 25129141 TI - Results of a comparative study analyzing octogenarians with renal cell carcinoma in a competing risk analysis with patients in the seventh decade of life. AB - OBJECTIVES: To analyze clinicopathological features and survival of surgically treated patients with renal cell carcinoma (RCC) >= 80 years of age in comparison with patients between the ages of 60 and 70 years. MATERIALS AND METHODS: The data for 2,516 patients with a median follow-up of 57 months were retrieved from a multinational database (Collaborative Research on Renal Neoplasms Association [CORONA]), including data for 6,234 consecutive patients with RCC after radical or partial nephrectomy. Comparative analysis of clinicopathological features of 241 octogenarians (3.9% of the database) and 2,275 reference patients between the ages of 60 and 70 years (36.5%) was performed. Multivariable regression analysis adjusted for competing risks was applied to identify the effect of advanced age on cancer-specific mortality (CSM) and other-cause mortality (OCM). Furthermore, instrumental variable analysis was employed to reduce residual confounding by unmeasured parameters. RESULTS: Significantly more women were present (50% vs. 40%, P = 0.004), and significantly less often nephron-sparing surgery was performed in octogenarians compared with the reference group (11% vs. 20%, P<0.001). Although median tumor size and stages did not significantly defer, older patients less often had advanced or metastatic disease (N+/M1) (4.6% vs. 9.6%, P = 0.009). On multivariable analysis, higher CSM (hazard ratio = 1.48, P = 0.042) and OCM rates (hazard ratio = 4.32, P<0.001) were detectable in octogenarians (c-indices = 0.85 and 0.72, respectively). Integration of the variable age group in multivariable models significantly increased the predictive accuracy regarding OCM (6%, P<0.001), but not for CSM. Limitations are based on the retrospective study design. CONCLUSIONS: Octogenarian patients with RCC significantly differ in clinical features and display significantly higher CSM and OCM rates in comparison with their younger counterparts. PMID- 25129142 TI - Predictors of 30-day acute kidney injury following radical and partial nephrectomy for renal cell carcinoma. AB - INTRODUCTION: Patients with renal cell carcinoma who were treated with radical nephrectomy (RN) or partial nephrectomy (PN) are at risk of postoperative acute kidney injury (AKI), and in consequence, short- and long-term adverse outcomes. We sought to identify independent predictors of 30-day AKI in patients undergoing RN or PN. MATERIALS AND METHODS: Between 2005 and 2011, patients who underwent RN or PN for renal cell carcinoma within the National Surgical Quality Improvement Program data set were identified. Patients with preexisting severe renal failure, defined as a preoperative estimated glomerular filtration rate<30 ml/min/1.73 m(2), were excluded from the analyses. AKI was defined as an elevation of serum creatinine>2mg/dl above baseline or the need for dialysis within 30 days of surgery. Univariable and multivariable logistic regression analyses were used to examine the association between preoperative factors and the risk of postoperative AKI. RESULTS: Overall, 1,944 (58.6%) and 1,376 (41.4%) patients underwent RN and PN, respectively. Overall, 1.8% of the patients included in the study experienced AKI within an average of 5.4 days after RN or PN. Independent predictors for AKI included obesity (odds ratio [OR] = 2.24, P = 0.04), history of neurovascular disease (OR = 5.29, P<0.001), and a preoperative chronic kidney disease stage II (OR = 10.00, P = 0.03) or stage III (OR = 26.49, P = 0.02). Furthermore, RN (OR = 2.87, P = 0.02) or the open approach (OR = 2.18, P = 0.04) was significantly associated with postoperative AKI. AKI was significantly associated with adverse postoperative outcomes, such as prolonged length of stay, occurrence of any complication, and mortality (all P <0.001). CONCLUSIONS: The assessment of preoperative kidney function and comorbidity status is essential to identify patients at risk of postoperative AKI. In addition to preoperative chronic kidney disease stages II and III, neurovascular disease, obesity, and surgical approach (RN or open) represent predictors of 30-day AKI. Careful patient selection as well as preoperative planning may help reduce this unfavorable postoperative outcome. PMID- 25129143 TI - Human somatic cell mutagenesis creates genetically tractable sarcomas. AB - Creating spontaneous yet genetically tractable human tumors from normal cells presents a fundamental challenge. Here we combined retroviral and transposon insertional mutagenesis to enable cancer gene discovery starting with human primary cells. We used lentiviruses to seed gain- and loss-of-function gene disruption elements, which were further deployed by Sleeping Beauty transposons throughout the genome of human bone explant mesenchymal cells. De novo tumors generated rapidly in this context were high-grade myxofibrosarcomas. Tumor insertion sites were enriched in recurrent somatic copy-number aberration regions from multiple cancer types and could be used to pinpoint new driver genes that sustain somatic alterations in patients. We identified HDLBP, which encodes the RNA-binding protein vigilin, as a candidate tumor suppressor deleted at 2q37.3 in greater than one out of ten tumors across multiple tissues of origin. Hybrid viral-transposon systems may accelerate the functional annotation of cancer genomes by enabling insertional mutagenesis screens in higher eukaryotes that are not amenable to germline transgenesis. PMID- 25129144 TI - JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. AB - The analysis of individuals with severe congenital neutropenia (SCN) may shed light on the delicate balance of factors controlling the differentiation, maintenance and decay of neutrophils. We identify 9 distinct homozygous mutations in the JAGN1 gene encoding Jagunal homolog 1 in 14 individuals with SCN. JAGN1 mutant granulocytes are characterized by ultrastructural defects, a paucity of granules, aberrant N-glycosylation of multiple proteins and increased incidence of apoptosis. JAGN1 participates in the secretory pathway and is required for granulocyte colony-stimulating factor receptor-mediated signaling. JAGN1 emerges as a factor that is necessary in the differentiation and survival of neutrophils. PMID- 25129145 TI - Jagunal homolog 1 is a critical regulator of neutrophil function in fungal host defense. AB - Neutrophils are key innate immune effector cells that are essential to fighting bacterial and fungal pathogens. Here we report that mice carrying a hematopoietic lineage-specific deletion of Jagn1 (encoding Jagunal homolog 1) cannot mount an efficient neutrophil-dependent immune response to the human fungal pathogen Candida albicans. Global glycobiome analysis identified marked alterations in the glycosylation of proteins involved in cell adhesion and cytotoxicity in Jagn1 deficient neutrophils. Functional analysis confirmed marked defects in neutrophil migration in response to Candida albicans infection and impaired formation of cytotoxic granules, as well as defective myeloperoxidase release and killing of Candida albicans. Treatment with granulocyte/macrophage colony-stimulating factor (GM-CSF) protected mutant mice from increased weight loss and accelerated mortality after Candida albicans challenge. Notably, GM-CSF also restored the defective fungicidal activity of bone marrow cells from humans with JAGN1 mutations. These data directly identify Jagn1 (JAGN1 in humans) as a new regulator of neutrophil function in microbial pathogenesis and uncover a potential treatment option for humans. PMID- 25129148 TI - Influence of transgenic rice expressing a fused Cry1Ab/1Ac protein on frogs in paddy fields. AB - As genetic engineering in plants is increasingly used to control agricultural pests, it is important to determine whether such transgenic plants adversely affect non-target organisms within and around cultivated fields. The cry1Ab/1Ac fusion gene from Bacillus thuringiensis (Bt) has insecticidal activity and has been introduced into rice line Minghui 63 (MH63). We evaluated the effect of transgenic cry1Ab/1Ac rice (Huahui 1, HH1) on paddy frogs by comparing HH1 and MH63 rice paddies with and without pesticide treatment. The density of tadpoles in rice fields was surveyed at regular intervals, and Cry1Ab/1Ac protein levels were determined in tissues of tadpoles and froglets collected from the paddy fields. In addition, Rana nigromaculata froglets were raised in purse nets placed within these experimental plots. The survival, body weight, feeding habits, and histological characteristics of the digestive tract of these froglets were analyzed. We found that the tadpole density was significantly decreased immediately after pesticide application, and the weight of R. nigromaculata froglets of pesticide groups was significantly reduced compared with no pesticide treatment, but we found no differences between Bt and non-Bt rice groups. Moreover, no Cry1Ab/1Ac protein was detected in tissue samples collected from 192 tadpoles and froglets representing all four experimental groups. In addition, R. nigromaculata froglets raised in purse seines fed primarily on stem borer and non target insects, and showed no obvious abnormality in the microstructure of their digestive tracts. Based on these results, we conclude that cultivation of transgenic cry1Ab/1Ac rice does not adversely affect paddy frogs. PMID- 25129147 TI - A genetic mechanism for Tibetan high-altitude adaptation. AB - Tibetans do not exhibit increased hemoglobin concentration at high altitude. We describe a high-frequency missense mutation in the EGLN1 gene, which encodes prolyl hydroxylase 2 (PHD2), that contributes to this adaptive response. We show that a variant in EGLN1, c.[12C>G; 380G>C], contributes functionally to the Tibetan high-altitude phenotype. PHD2 triggers the degradation of hypoxia inducible factors (HIFs), which mediate many physiological responses to hypoxia, including erythropoiesis. The PHD2 p.[Asp4Glu; Cys127Ser] variant exhibits a lower K(m) value for oxygen, suggesting that it promotes increased HIF degradation under hypoxic conditions. Whereas hypoxia stimulates the proliferation of wild-type erythroid progenitors, the proliferation of progenitors with the c.[12C>G; 380G>C] mutation in EGLN1 is significantly impaired under hypoxic culture conditions. We show that the c.[12C>G; 380G>C] mutation originated ~8,000 years ago on the same haplotype previously associated with adaptation to high altitude. The c.[12C>G; 380G>C] mutation abrogates hypoxia-induced and HIF-mediated augmentation of erythropoiesis, which provides a molecular mechanism for the observed protection of Tibetans from polycythemia at high altitude. PMID- 25129149 TI - Soil surface colonization by phototrophic indigenous organisms, in two contrasted soils treated by formulated maize herbicide mixtures. AB - Soil phototrophic microorganisms, contributors to soil health and food webs, share their particular metabolism with plants. Current agricultural practices employ mixtures of pesticides to ensure the crops yields and can potentially impair these non-target organisms. However despite this environmental reality, studies dealing the susceptibility of phototrophic microorganisms to pesticide mixtures are scarce. We designed a 3 months microcosm study to assess the ecotoxicity of realistic herbicide mixtures of formulated S-metolachlor (Dual Gold Safeneur((r))), mesotrione (Callisto((r))) and nicosulfuron (Milagro((r))) on phototrophic communities of two soils (Limagne vertisol and Versailles luvisol). The soils presented different colonizing communities, with diatoms and chlorophyceae dominating communities in Limagne soil and cyanobacteria and bryophyta communities in Versailles soil. The results highlighted the strong impairment of Dual Gold Safeneur((r)) treated microcosms on the biomass and the composition of both soil phototrophic communities, with no resilience after a delay of 3 months. This study also excluded any significant mixture effect on these organisms for Callisto((r)) and Milagro((r)) herbicides. We strongly recommend carrying on extensive soil studies on S-metolachlor and its commercial formulations, in order to reconsider its use from an ecotoxicological point of view. PMID- 25129151 TI - Management of pediatric and adolescent adnexal masses by gasless laparoendoscopic single-site surgery. AB - OBJECTIVE: To evaluate the safety and feasibility of gasless transumbilical laparoendoscopic single-site (LESS) surgery for the management of adnexal masses in pediatric and adolescent girls aged 19 years or younger. STUDY DESIGN: Retrospective study of 28 pediatric and adolescent girls each undergoing gasless LESS surgery and gasless multiport laparoscopic surgery for adnexal masses. In each case, laparoscopic surgery was performed by the abdominal-wall lift method under endotracheal general anesthesia. The two groups were compared for their patient demographics and surgical outcome measures. RESULTS: In the LESS surgery group, median age of the patients including three pre-menarcheal girls was 17.5 years. The most common symptom was abdominal pain. Median tumor diameter in the LESS surgery group was 7.4cm. There were no statistical differences in clinical features between LESS surgery and multiport laparoscopic surgery groups. In the LESS surgery group, adnexal masses were managed by unilateral cystectomy (n=20), unilateral salpingo-oophorectomy (n=5), bilateral cystectomy (n=2), and unilateral salpingectomy (n=1). Emergency LESS surgery was performed for seven cases due to adnexal torsion and one case due to cyst rupture. Preservation of affected ovary was not achieved in three emergency cases with adnexal torsion due to severe necrosis, and in one case each of recurrent mucinous cystadenoma and huge mucinous cystadenoma. In 24 adnexal masses from 22 girls who received adnexal cystectomy by LESS surgery, LESS-assisted extracorporeal cystectomy, was possible in 14 masses while intracorporeal cystectomy was required in other 10. In a case of dermoid cyst managed by LESS-assisted extracorporeal cystectomy, additional hemostasis was required by intracorporeal suturing due to laceration of utero-ovarian ligament. Median-excised tissue weight in the LESS surgery group was 111g. Significant differences between LESS surgery and multiport laparoscopic surgery groups were not noted in surgical outcomes and pathological diagnosis, except for significantly lower C-reactive protein value on postoperative day 3 in the LESS surgery group. CONCLUSION: Gasless LESS surgery for pediatric and adolescent adnexal masses is a safe and feasible alternative to multiport laparoscopic surgery. PMID- 25129150 TI - Evaluation of single-port laparoscopy for peritoneal carcinomatosis assessment in advanced ovarian cancer. AB - OBJECTIVES: Ovarian cancers are usually diagnosed at an advanced stage. The extent of the disease before surgery partly determines the ability to perform a complete cytoreduction. The peritoneal cancer index (PCI) is used to evaluate peritoneal carcinomatosis and has been validated in ovarian cancer and correlated with resectability. The aim of our study was to assess the feasibility of single port laparoscopy (SPL) for suspicion of advanced ovarian cancer and to describe the ability to calculate the PCI score at the time of laparoscopy. STUDY DESIGN: Between February 2011 and January 2013, 33 patients underwent SPL for suspected advanced ovarian cancer. Individual records for all patients were prospectively reviewed and analyzed. For each patient, we determined the PCI score. RESULTS: 33 patients underwent initial SPL, 85% had increased carcinological markers and 67% a radiological suspicion of peritoneal carcinomatosis. The median operative time was 90min. During SPL, 76% of patients underwent ascites evacuation; all patients had peritoneal cytology and peritoneal biopsies. Only 3 patients experienced perioperative complications. Two open conversions were recorded. Quotation of the PCI score was possible for all patients. Eighteen patients (55%) had a PCI score below 10; one had a maximal PCI score of 39. The PCI score was null for 9 patients. Non-browsing areas marked 8 procedures. CONCLUSIONS: SPL appeared to be feasible, with satisfying immediate results and postoperative outcome, compared to conventional laparoscopy. It allowed a satisfying exploration of the abdomino pelvic cavity and a good description of peritoneal carcinomatosis with only a few non-browsing PCI areas. PMID- 25129152 TI - Obstetric and perinatal outcomes of twin pregnancies conceived following IVF/ICSI treatment compared with spontaneously conceived twin pregnancies. AB - OBJECTIVE: Twin pregnancy is associated with increased obstetric and perinatal risk. There are conflicting reports on whether assisted conception (ART) further increases these risks. The aim of this study is to assess the obstetric and perinatal outcomes of twin pregnancies according to mode of conception. STUDY DESIGN: A retrospective study of all viable dichorionic-diamniotic (DCDA) twin pregnancies (n=539) delivered at Cork University Maternity Hospital, Ireland between 2009 and 2012, divided according to spontaneous conception (SC) and ART conception, specifically IVF or ICSI. RESULTS: The ART conceived group were on average 4 years older (36.8+/-4.23 vs 32.3+/-4.93 years) and more frequently nulliparous (73.7%; n=126 vs 36.1%; n=133) than their SC counterparts (p<0.001). There was no significant difference in maternal antenatal complications. ART twins were twice as likely to be delivered by caesarean section (CS) (OR 2.35; 95% CI 1.76-3.14). There was no significant difference in the rates of preterm birth or NICU admission according to mode of conception. ART conceived twins were almost twice as likely to be delivered moderately preterm (32-33(+6)) (OR 1.98, 95% CI 1.21-3.23) and were more likely to have RDS and neonatal hypoglycaemia CONCLUSIONS: Twin pregnancy, irrespective of mode of conception, carries an increased risk of morbidity and mortality for both mother and babies and therefore couples should be counselled regarding the increased risk of iatrogenic twinning associated with double embryo transfer. However, for those that do conceive twins, they can be advised that assisted conception conveys no significant disadvantage over naturally conceived twin pregnancies. PMID- 25129153 TI - Predictive value of combined serum biomarkers for adverse pregnancy outcomes. AB - OBJECTIVE: To determine if a combination of first and second trimester serum biomarkers (pregnancy-associated plasma protein A (PAPP-A), free betahCG, and maternal serum alpha-fetoprotein (msAFP)) may be utilized to develop a predictive model for adverse pregnancy outcomes. STUDY DESIGN: We conducted a retrospective analysis including all women who delivered at our institution between 2007 and 2010. We estimated the area under the ROC curve (AUC) to compare predictive abilities of PAPP-A, free betahCG, and msAFP singularly, and in combination for adverse pregnancy outcomes. We sought to predict the risks of preeclampsia, preterm delivery (PTD, <37 weeks gestational age) and low birth weight (LBW, <2500g). Using logistic regression analysis, we created models that controlled for maternal age, race, parity, body mass index, and histories of chronic hypertension and tobacco use. RESULTS: The final sample included 2199 women. Determining the AUC and optimal cutoff probability values for each of the biomarkers, we found that for PTD and LBW, the combination of all three biomarkers was most predictive, while for preeclampsia the combination of msAFP and PAPP-A was most predictive. The AUC of the three biomarker combination to detect adverse pregnancy outcomes are as follows: LBW 67%, PTD 72%, and preeclampsia 77%. We created race-specific logistic regression models to predict the risk probabilities. To illustrate, the predictive probability for a 33-year old African American, nullipara with a BMI of 50, chronic hypertension, tobacco use, PAPP-A 0.3, msAFP 2.0 and free betahCG 0.98 MOMs are: PTD 59%, LBW 61% and Preeclampsia 91%. CONCLUSION: The combination of biomarkers currently utilized in Down syndrome screening may also be used to predict additional adverse pregnancy outcomes. Further studies are needed to determine optimal maternal and fetal surveillance, if and when increased risks are identified. PMID- 25129154 TI - Personal birth preferences and actual mode of delivery outcomes of obstetricians and gynaecologists in South West England; with comparison to regional and national birth statistics. AB - OBJECTIVE: To determine personal birth preferences of obstetricians in various clinical scenarios, in particular elective caesarean section for maternal request. To determine actual rates of modes of deliveries amongst the same group. To compare the obstetrician's mode of delivery rates, to the general population. STUDY DESIGN: Following ethical approval, a piloted online survey link was sent via email to 242 current obstetricians and gynaecologists, (consultants and trainees) in South West England. Mode of delivery results were compared to regional and national population data, using Hospital Episode Statistics and subjected to statistical analysis. RESULTS: The response rate was 68%. 90% would hypothetically plan a vaginal delivery, 10% would consider a caesarean section in an otherwise uncomplicated primiparous pregnancy. Of the 94/165 (60%) respondents with children (201 children), mode of delivery for the first born child; normal vaginal delivery 48%, caesarean section 26.5% (elective 8.5%, emergency 18%), instrumental 24.5% and vaginal breech 1%. Only one chose an elective caesarean for maternal request. During 2006-2011 obstetricians have the same overall actual modes of birth as the population (p=0.9). CONCLUSIONS: Ten percent of obstetricians report they would consider requesting caesarean section for themselves/their partner, which is the lowest rate reported within UK studies. However only 1% actually had a caesarean solely for maternal choice. When compared to regional/national statistics obstetricians currently have modes of delivery that are not significantly different than the population and suggests that they choose non interventional delivery if possible. PMID- 25129146 TI - Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. AB - We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 * 10(-20)) and rs1642764 at 17p13.1 (per allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 * 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 * 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC. PMID- 25129155 TI - Atmospheric pollutants in fog and rain events at the northwestern mountains of the Iberian Peninsula. AB - Atmospheric polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) and exist in gas and particle phases, as well as dissolved or suspended in precipitation (fog or rain). While the hydrosphere is the main reservoir for PAHs, the atmosphere serves as the primary route for global transport of PCBs. In this study, fog and rain samples were collected during fourteen events from September 2011 to April 2012 in the Xistral Mountains, a remote range in the NW Iberian Peninsula. PAH compounds [especially of low molecular weight (LMW)] were universally found, but mainly in the fog-water samples. The total PAH concentration in fog-water ranged from non detected to 216 ng.L(-1) (mean of 45 ng.L(-1)), and was much higher in fall than in winter. Total PAH levels in the rain and fog events varied from non-detected to 1272 and 33 ng.L(-1) for, respectively, LMW and high molecular weight (HMW) PAHs. Diagnostic ratio analysis (LMW PAHs/HMW PAHs) suggested that petroleum combustion was the dominant contributor to PAHs in the area. Total PCB levels in the rain and fog events varied from non-detected to 305 and 91 ng.L(-1) for, respectively, PCBs with 2-3 Cl atoms and 5-10 Cl atoms. PCBs, especially those with 5-10 Cl atoms, were found linked to rain events. The occurrence of the most volatile PCBs, PCBs with 2-3 Cl atoms, is related to wind transport from far away sources, whereas the occurrence of PCBs with 5-10 Cl atoms seems to be related with the increase of its deposition during rainfall at the end of summer and fall. The movement of this fraction of PCBs is facilitated by its binding to air suspended particles, whose concentrations usually show an increase as the result of a prolonged period of drought in summer. PMID- 25129156 TI - Arsenic species in raw and cooked rice: implications for human health in rural Bengal. AB - This study compares the concentrations of total and different species of arsenic (As) in 29 pairs of raw and cooked rice samples collected from households in an area of West Bengal affected by endemic arsenicism. The aim is to investigate the effects of indigenous cooking practice of the rural villagers on As accumulation and speciation in cooked rice. It is found that inorganic As is the predominant species in both raw (93.8%) and cooked rice (88.1%). Cooking of rice with water low in As (<10 MUg L(-1)) significantly decreases the total and inorganic As content in cooked rice compared to raw rice. Arsenic concentration is mainly decreased during boiling of rice grains with excess water. Washing of rice grains with low As water has negligible effect on grain As concentration. The study suggests that rice cooking with low As water by the villagers is a beneficial risk reduction strategy. Despite reductions in As content in cooked rice because of cooking with low As water, the consumption of cooked rice represents a significant health threat (in terms of chronic As toxicity) to the study population. PMID- 25129157 TI - The sub-lethal effects and tissue concentration of the human pharmaceutical atenolol in rainbow trout (Oncorhynchus mykiss). AB - Atenolol is a highly prescribed anti-hypertensive pharmaceutical and a member of the group of beta-blockers. It has been detected at concentrations ranging from ng L(-1) to low MUg L(-1) in waste and surface waters. The present study aimed to assess the sub-lethal effects of atenolol on rainbow trout (Oncorhynchus mykiss) and to determine its tissue-specific bioconcentration. Juvenile rainbow trout were exposed for 21 and 42 days to three concentration levels of atenolol (1 MUg L(-1) - environmentally relevant concentration, 10 MUg L(-1), and 1000 MUg L( 1)). The fish exposed to 1 MUg L(-1) atenolol exhibited a higher lactate content in the blood plasma and a reduced haemoglobin content compared with the control. The results show that exposure to atenolol at concentrations greater than or equal to 10 MUg L(-1) significantly reduces both the haematocrit value and the glucose concentration in the blood plasma. The activities of the studied antioxidant enzymes (catalase and superoxide dismutase) were not significantly affected by atenolol exposure, and only the highest tested concentration of atenolol significantly reduced the activity of glutathione reductase. The activities of selected CYP450 enzymes were not affected by atenolol exposure. The histological changes indicate that atenolol has an effect on the vascular system, as evidenced by the observed liver congestion and changes in the pericardium and myocardium. Atenolol was found to have a very low bioconcentration factor (the highest value found was 0.27). The bioconcentration levels followed the order liver>kidney>muscle. The concentration of atenolol in the blood plasma was below the limit of quantification (2.0 ng g(-1)). The bioconcentration factors and the activities of selected CYP450 enzymes suggest that atenolol is not metabolised in the liver and may be excreted unchanged. PMID- 25129158 TI - Mercury in organisms from the Northwestern Mediterranean slope: importance of food sources. AB - Mercury (Hg) is a global threat for marine ecosystems, especially within the Mediterranean Sea. The concern is higher for deep-sea organisms, as the Hg concentration in their tissues is commonly high. To assess the influence of food supply at two trophic levels, total Hg concentrations and carbon and nitrogen stable isotope ratios were determined in 7 species (4 teleosts, 2 sharks, and 1 crustacean) sampled on the upper part of the continental slope of the Gulf of Lions (Northwestern Mediterranean Sea), at depths between 284 and 816 m. Mean Hg concentrations ranged from 1.30+/-0.61 to 7.13+/-7.09 MUg g(-1) dry mass, with maximum values observed for small-spotted catshark Scyliorhinus canicula. For all species except blue whiting Micromesistius poutassou, Hg concentrations were above the health safety limits for human consumption defined by the European Commission, with a variable proportion of the individuals exceeding limits (from 23% for the Norway lobster Nephrops norvegicus to 82% for the blackbelly rosefish Helicolenus dactylopterus). Measured concentrations increased with increasing trophic levels. Carbon isotopic ratios measured for these organisms demonstrated that settling phytoplanktonic organic matter is not only the main source fueling trophic webs but also the carrier of Hg to this habitat. Inter- and intraspecific variations of Hg concentrations revealed the importance of feeding patterns in Hg bioaccumulation. In addition, biological parameters, such as growth rate or bathymetric range explain the observed contamination trends. PMID- 25129159 TI - Defining fish community structure in Lake Winnipeg using stable isotopes (delta(13)C, delta(15)N, delta(34)S): implications for monitoring ecological responses and trophodynamics of mercury & other trace elements. AB - The ecological integrity of freshwater lakes is influenced by atmospheric and riverine deposition of contaminants, shoreline development, eutrophication, and the introduction of non-native species. Changes to the trophic structure of Lake Winnipeg, Canada, and consequently, the concentrations of contaminants and trace elements measured in tissues of native fishes, are likely attributed to agricultural runoff from the 977,800 km(2) watershed and the arrival of non native zooplankters and fishes. We measured delta(13)C, delta(15)N, and delta(34)S along with concentrations of 15 trace elements in 17 native fishes from the north and south basins of Lake Winnipeg in 2009 and 2010. After adjusting for differences in isotopic baseline values between the two basins, fishes in the south basin had consistently higher delta(13)C and delta(34)S, and lower delta(15)N. We found little evidence of biomagnification of trace elements at the community level, but walleye (Sander vitreus) and freshwater drum (Aplodinotus grunniens) had higher mercury and selenium concentrations with increased trophic position, coincident with increased piscivory. There was evidence of growth dilution of cobalt, copper, manganese, molybdenum, thallium, and vanadium, and bioaccumulation of mercury, which could be explained by increases in algal (and consequently, lake and fish) productivity. We conclude that the north and south basins of Lake Winnipeg represent very different communities with different trophic structures and trace element concentrations. PMID- 25129161 TI - Accumulation and elimination of polychlorinated dibenzo-p-dioxins and dibenzofurans in mule ducks. AB - In Taiwan, a food safety crisis involving a presence of high concentrations of dioxin residues in duck eggs occurred in 2004. The dioxin content in duck meat sampled from supermarkets was also reported to be substantially higher than in products from other farm animals. Despite increased awareness of the potential for contamination and exposure to dioxins, the accumulation and elimination of dioxins in ducks have not been well characterized. In the present study, mule ducks were fed capsules containing polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) for 14 days and the trial was continued for another 28 days without PCDD/Fs supplementation. Ducks were sacrificed on the 14th, 28th, and 42nd days from the beginning of administration and samples of abdominal fat, breast, and liver tissue were obtained. The concentrations of PCDD/Fs were analyzed in the samples to investigate their distribution and elimination in various duck tissues. The bioaccumulation of PCDD/Fs in ducks was found to be tissue-dependent. In the abdominal fat, the bioconcentration factor was negatively correlated with the degree of chlorination. Conversely, more chlorinated PCDD/Fs (hexa- or hepta-congeners) were associated with higher bioconcentration in the liver and breast tissue. In terms of the efficiency of PCDD/Fs elimination, the liver was found to be the fastest, followed by the breast and the abdominal fat. The clearance rate positively correlated with the degree of chlorination, as determined by comparing the apparent elimination rate constant (k) of PCDD/Fs in various tissues. Overall, lower k values observed in this study imply that mule ducks have a reduced clearance of PCDD/Fs in comparison with layer and broiler chickens. PMID- 25129160 TI - Remediation of petroleum hydrocarbon-contaminated sites by DNA diagnosis-based bioslurping technology. AB - The application of effective remediation technologies can benefit from adequate preliminary testing, such as in lab-scale and Pilot-scale systems. Bioremediation technologies have demonstrated tremendous potential with regards to cost, but they cannot be used for all contaminated sites due to limitations in biological activity. The purpose of this study was to develop a DNA diagnostic method that reduces the time to select contaminated sites that are good candidates for bioremediation. We applied an oligonucleotide microarray method to detect and monitor genes that lead to aliphatic and aromatic degradation. Further, the bioremediation of a contaminated site, selected based on the results of the genetic diagnostic method, was achieved successfully by applying bioslurping in field tests. This gene-based diagnostic technique is a powerful tool to evaluate the potential for bioremediation in petroleum hydrocarbon contaminated soil. PMID- 25129162 TI - Distribution, sources and composition of antibiotics in sediment, overlying water and pore water from Taihu Lake, China. AB - The occurrence of 15 antibiotics classified as sulphonamides, fluoroquinolones, macrolides, tetracyclines and trimethoprim in sediment, overlying water, and pore water matrices in Taihu Lake, China was studied. The total concentrations were from 4.1 MUg/kg to 731 MUg/kg, from 127 ng/L to 1210 ng/L, and from 1.5 ng/L to 216 ng/L in sediment, overlying water and pore water, respectively. Antibiotics in different locations originated from various sources, depending on human, agricultural and aquacultural activities. Composition analysis indicated that human-derived and animal-derived drugs significantly contributed to the total contamination of antibiotics in the lake, indicating the high complexity of contamination sources in Taihu Lake Basin. The in situ sediment-pore water partitioning coefficients were generally greater than sediment-overlying water partitioning coefficients, suggesting continuous inputs into the lake water. This study shows that antibiotics are ubiquitous in all compartments in Taihu Lake, and their potential hazards to the aquatic ecosystem need further investigation. PMID- 25129163 TI - Trends of ambient fine particles and major chemical components in the Pearl River Delta region: observation at a regional background site in fall and winter. AB - In the fall and winter of 2007 to 2011, 167 24-h quartz filter-based fine particle (PM2.5) samples were collected at a regional background site in the central Pearl River Delta. The PM2.5 showed an annual reduction trend with a rate of 8.58 MUg m(-3) (p<0.01). The OC component of the PM2.5 reduced by 1.10 MUg m( 3) yr(-1) (p<0.01), while the reduction rates of sulfur dioxide (SO2) and sulfate (SO4(2-)) were 10.2 MUg m(-3) yr(-1) (p<0.01) and 1.72 MUg m(-3) yr(-1) (p<0.01), respectively. In contrast, nitrogen oxides (NOx) and nitrate (NO(3-)) presented growth trends with rates of 6.73 MUg m(-3) yr(-1) (p<0.05) and 0.79 MUg m(-3) yr( 1) (p<0.05), respectively. The PM2.5 reduction was mainly related to the decrease of primary OC and SO4(2-), and the enhanced conversion efficiency of SO2 to SO4(2 ) was related to an increase in the atmospheric oxidizing capacity and a decrease in aerosol acidity. The discrepancy between the annual trends of NOx and NO3(-) was attributable to the small proportion of NO3(-) in the total nitrogen budget. CAPSULE ABSTRACT: Understanding annual variations of PM2.5 and its chemical composition is crucial in enabling policymakers to formulate and implement control strategies on particulate pollution. PMID- 25129164 TI - Intraluminal lesion of the pulmonary artery: A diagnostic challenge. PMID- 25129165 TI - Workplace accidents, absenteeism and productivity in patients with sleep apnea. AB - INTRODUCTION: Obstructive sleep apnea-hypopnea syndrome (OSAHS) has health related outcomes, but the impact of OSAHS on occupational health has been scarcely studied. The aim of this study was to evaluate the effect of OSAHS on workplace accidents, absenteeism and productivity. METHOD: One hundred eighty-two OSAHS patients and 71 healthy subjects completed the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index and the Spanish IMPALA (Impact of Disease on Work Productivity) index and answered various questions on workplace accidents and sick leave. Participants were classified to an OSAHS group or a non-OSAHS group according to polysomnography results. RESULTS: Patients with OSAHS had more sick leave lasting longer than 30days (16.6% vs. 7%, P=.049) and lower productivity (63.80% vs. 83.20%, P=.000) than subjects without OSAHS, although the rate of workplace accidents was similar in both groups (27.4% vs 25.4%; P>.050). None of the OSAHS-related variables was associated with workplace accidents. A diagnosis of OSAHS was related with absenteeism. Psychological distress and OSAHS were related with productivity. CONCLUSIONS: OSAHS causes limitations in the working lives of patients and leads to a higher incidence of sick leave and lower productivity. A diagnosis of OSAHS was the variable with most influence on the working lives of patients. PMID- 25129166 TI - A comparison of optimisation methods and knee joint degrees of freedom on muscle force predictions during single-leg hop landings. AB - The aim of this paper was to compare the effect of different optimisation methods and different knee joint degrees of freedom (DOF) on muscle force predictions during a single legged hop. Nineteen subjects performed single-legged hopping manoeuvres and subject-specific musculoskeletal models were developed to predict muscle forces during the movement. Muscle forces were predicted using static optimisation (SO) and computed muscle control (CMC) methods using either 1 or 3 DOF knee joint models. All sagittal and transverse plane joint angles calculated using inverse kinematics or CMC in a 1 DOF or 3 DOF knee were well-matched (RMS error<3 degrees ). Biarticular muscles (hamstrings, rectus femoris and gastrocnemius) showed more differences in muscle force profiles when comparing between the different muscle prediction approaches where these muscles showed larger time delays for many of the comparisons. The muscle force magnitudes of vasti, gluteus maximus and gluteus medius were not greatly influenced by the choice of muscle force prediction method with low normalised root mean squared errors (<48%) observed in most comparisons. We conclude that SO and CMC can be used to predict lower-limb muscle co-contraction during hopping movements. However, care must be taken in interpreting the magnitude of force predicted in the biarticular muscles and the soleus, especially when using a 1 DOF knee. Despite this limitation, given that SO is a more robust and computationally efficient method for predicting muscle forces than CMC, we suggest that SO can be used in conjunction with musculoskeletal models that have a 1 or 3 DOF knee joint to study the relative differences and the role of muscles during hopping activities in future studies. PMID- 25129167 TI - Investigation of impact loading rate effects on the ligamentous cervical spinal load-partitioning using finite element model of functional spinal unit C2-C3. AB - The cervical spine functions as a complex mechanism that responds to sudden loading in a unique manner, due to intricate structural features and kinematics. The spinal load-sharing under pure compression and sagittal flexion/extension at two different impact rates were compared using a bio-fidelic finite element (FE) model of the ligamentous cervical functional spinal unit (FSU) C2-C3. This model was developed using a comprehensive and realistic geometry of spinal components and material laws that include strain rate dependency, bone fracture, and ligament failure. The range of motion, contact pressure in facet joints, failure forces in ligaments were compared to experimental findings. The model demonstrated that resistance of spinal components to impact load is dependent on loading rate and direction. For the loads applied, stress increased with loading rate in all spinal components, and was concentrated in the outer intervertebral disc (IVD), regions of ligaments to bone attachment, and in the cancellous bone of the facet joints. The highest stress in ligaments was found in capsular ligament (CL) in all cases. Intradiscal pressure (IDP) in the nucleus was affected by loading rate change. It increased under compression/flexion but decreased under extension. Contact pressure in the facet joints showed less variation under compression, but increased significantly under flexion/extension particularly under extension. Cancellous bone of the facet joints region was the only component fractured and fracture occurred under extension at both rates. The cervical ligaments were the primary load-bearing component followed by the IVD, endplates and cancellous bone; however, the latter was the most vulnerable to extension as it fractured at low energy impact. PMID- 25129168 TI - Challenges towards the elimination of Human African Trypanosomiasis in the sleeping sickness focus of Campo in southern Cameroon. AB - The sleeping sickness focus of Campo lies along the Atlantic coast and extends along the Ntem River, which constitutes the Cameroonian and Equatorial Guinean border. It is a hypo-endemic focus with the disease prevalence varying from 0.3 to 0.86% during the last few decades. Investigations on animal reservoirs revealed a prevalence of Trypanosoma brucei gambiense of 0.6% in wild animals and 4.83% in domestic animals of this focus. From 2001 to 2012, about 19 931 tsetse were collected in this focus and five tsetse species including Glossina palpalis palpalis, G. pallicera, G. nigrofusca, G. tabaniformis and G. caliginea were identified. The analysis of blood meals of these flies showed that they feed on human, pig, goat, sheep, and wild animals such as antelope, duiker, wild pig, turtle and snake. The percentage of blood meals taken on these hosts varies according to sampling periods. For instance, 6.8% of blood meals from pig were reported in 2004 and 22% in 2008. This variation is subjected to considerable evolutions because the Campo HAT focus is submitted to socio-economic mutations including the reopening of a new wood company, the construction of autonomous port at "Kribi" as well as the dam at "Memve ele". These activities will bring more that 3000 inhabitants around Campo and induce the deforestation for the implementation of farmlands as well as breeding of domestic animals. Such mutations have impacts on the transmission and the epidemiology of sleeping sickness due to the modification of the fauna composition, the nutritional behavior of tsetse, the zoophilic/anthropophilic index. To achieve the elimination goal in the sleeping sickness focus of Campo, we report in this paper the current epidemiological situation of the disease, the research findings of the last decades notably on the population genetics of trypanosomes, the modifications of nutritional behavior of tsetse, the prevalence of T. b. gambiense in humans, domestic and wild animals. An overview on the types of mutations occurring in the region has been raised and a discussion on the strategies that can be implemented to achieve the elimination of the disease has been made. PMID- 25129169 TI - Sulfonamide inhibition study of the carbonic anhydrases from the bacterial pathogen Porphyromonas gingivalis: the beta-class (PgiCAb) versus the gamma-class (PgiCA) enzymes. AB - The oral pathogenic bacterium Porphyromonas gingivalis, encodes for two carbonic anhydrases (CAs, EC 4.2.1.1) one belonging to the gamma-class (PgiCA) and another one to the beta-class (PgiCAb). This last enzyme has been cloned and characterized here for its inhibition profile with the main class of CA inhibitors, the sulfonamides. Many of the clinically used sulfonamides as well as simple aromatic/heterocyclic sulfonamides were ineffective as PgiCAb inhibitors whereas better inhibition was observed with simple derivatives such as sulfanilamide, metanilamide, 4-aminoalkylbenzenesulfonamides (KIs of 364-475nM). The halogenosulfanilamides incorporating heavy halogens, 4-hydroxy- and 4 hydroxyalkyl-benzenesulfonamides, were also micromolar, ineffective PgiCAb inhibitors. The best inhibitors of the beta-class enzyme were acetazolamide and ethoxzolamide, with KIs of 214-280nM. Interestingly, the gamma-class enzyme was much more sensitive to sulfonamide inhibitors compared to the beta-class one, PgiCAb. Identification of potent and possibly selective inhibitors of PgiCAb/PgiCA may lead to pharmacological tools useful for understanding the physiological role(s) of these enzymes, since this bacterium is the main causative agent of periodontitis and few treatment options are presently available. PMID- 25129170 TI - 'Carba'-carfentanil (trans isomer): a MU opioid receptor (MOR) partial agonist with a distinct binding mode. AB - There is strong evidence to indicate that a positively charged nitrogen of endogenous and exogenous opioid ligands forms a salt bridge with the Asp residue in the third transmembrane helix of opioid receptors. To further examine the role of this electrostatic interaction in opioid receptor binding and activation, we synthesized 'carba'-analogues of the highly potent MU opioid analgesic carfentanil (3), in which the piperidine nitrogen was replaced with a carbon. The resulting trans isomer (8b) showed reduced, but still significant MOR binding affinity (Ki(MU)=95.2nM) with no MOR versus DOR binding selectivity and was a MOR partial agonist. The cis isomer (8a) was essentially inactive. A MOR docking study indicated that 8b bound to the same binding pocket as parent 3, but its binding mode was somewhat different. A re-evaluation of the uncharged morphine derivative N-formylnormorphine (9) indicated that it was a weak MOR antagonist showing no preference for MOR over KOR. Taken together, the results indicate that deletion of the positively charged nitrogen in MU opioid analgesics reduces MOR binding affinity by 2-3 orders of magnitude and may have pronounced effects on the intrinsic efficacy and on the opioid receptor selectivity profile. PMID- 25129171 TI - Design, synthesis, biological evaluation of substituted benzofurans as DNA gyraseB inhibitors of Mycobacterium tuberculosis. AB - DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase and is a well-established and validated target for the development of novel therapeutics. By adapting the medium throughput screening approach, we present the discovery and optimization of ethyl 5-(piperazin-1-yl) benzofuran-2 carboxylate series of mycobacterial DNA gyraseB inhibitors, selected from Birla Institute of Technology and Science (BITS) database chemical library of about 3000 molecules. These compounds were tested for their biological activity; the compound 22 emerged as the most active potent lead with an IC50 of 3.2+/-0.15MUM against Mycobacterium smegmatis DNA gyraseB enzyme and 0.81+/-0.24MUM in MTB supercoiling activity. Subsequently, the binding of the most active compound to the DNA gyraseB enzyme and its thermal stability was further characterized using differential scanning fluorimetry method. PMID- 25129172 TI - Comorbidity of psychiatric disorders with Internet addiction in a clinical sample: the effect of personality, defense style and psychopathology. AB - This study aims to contribute to the understanding of underlying causes for the development of Internet Addiction Disorder (IAD) and assess comorbidity with other mental disorders through the analysis of data from a clinical sample of college students who presented for treatment of IAD. The clinical sample of our study has demonstrated a high percentage of comorbidity with Axis I and II disorders, while the temporal precedence of the establishment of those disorders cannot lead to specific conclusions. Half of the sample (25/50) presented with comorbidity of another Axis I disorder and 38% (19/50) with a concurrent Axis II personality disorder. The majority of Axis I disorders (51.85%) were reported before the onset of IAD, 33.3% after the onset while it was unclear in 14.81% of cases. The examination of a path model demonstrated that important contributions to the understanding of this disorder can be made through concepts from the neurobiological, trait personality paradigm, as well as from the psychodynamic defense style paradigm. Comorbid psychopathology can further exacerbate the presentation of IAD through a direct link, regardless of the underlying personality structure. The clinician treating IAD patients should complete a clinical evaluation for comorbid Axis I and II diagnoses since their presence may signify a more serious presentation. PMID- 25129174 TI - Emergency department triage. Why and how? PMID- 25129173 TI - Correlates of use of electronic cigarettes versus nicotine replacement therapy for help with smoking cessation. AB - INTRODUCTION: Electronic- or e-cigarettes are nicotine-delivery devices commonly used by smokers to quit or reduce smoking. At present, not much is known about the characteristics of smokers who specifically try e-cigarettes to quit smoking compared to the nicotine replacement therapy (NRT) products approved by the U.S. Food and Drug Administration (FDA). Determining the characteristics of smokers who are likely to choose e-cigarettes as cessation aids would help develop strategies to impart valid information about e-cigarettes to such smokers as facts regarding the safety and utility of e-cigarettes emerge. METHODS: This study is based on 834 daily smokers [mean age=45.8 (standard deviation=13)] from Hawaii. Demographic, smoking- and cessation-related variables were examined as correlates of ever use of e-cigarette only or any FDA-approved NRT product only or both as cessation aids. RESULTS: Results indicated that younger smokers, non White smokers, and smokers reporting higher income, lower nicotine dependence, shorter smoking history, and higher lifetime quit attempts were more likely to have tried e-cigarettes but not NRT products for help with smoking cessation. CONCLUSION: Smokers who are attracted to use e-cigarettes but not FDA-approved NRT products may differ from smokers who are likely to have used NRT products but not e-cigarettes in terms of demographic (e.g., age, ethnicity) and smoking- or cessation-related characteristics (e.g., nicotine dependence, quit attempts). Given the lack of knowledge regarding the health effects of e-cigarettes and their efficacy as cessation aids, future research needs to continue characterizing smokers who are likely to use e-cigarettes for smoking cessation. PMID- 25129175 TI - Update in the management of allergic fungal sinusitis. AB - Over the last 3 decades, allergic fungal sinusitis (AFS) has been defined as a clinically and pathologically distinct form of chronic rhinosinusitis. The etiology, pathogenesis, and natural history of the disease has not been fully understood, and the appropriate treatment for AFS is also controversial. The management of AFS includes a combination of functional endoscopic sinus surgery and medical treatment in the form of pre- and post-operative systemic steroids, local steroids, and allergic immunotherapy. Close follow-up and coordination between the surgeon and physician is needed for optimum outcome. Despite aggressive medical and surgical treatment, high recurrence rates have been reported. In this review, we study the current literature and data regarding various surgical and non-surgical treatment options for AFS. PMID- 25129176 TI - Microribonucleic acids and vascular restenosis. AB - Microribonucleic acids (miRNAs) are small non-coding RNAs, which control diverse cellular functions by either promoting degradation or inhibiting target messenger RNA translation. An aberrant expression profile of miRNAs has been linked to human diseases, including cardiovascular dysfunction. This review summarizes the latest insights in the identification of vascular-specific miRNAs and the underlying mechanisms for their roles in vascular restenosis mainly by influencing the proliferation and migration of vascular smooth muscle cell. Here, we discuss miRNA-based drug and gene therapy in vascular restenosis. PMID- 25129177 TI - Systematic review of quality of care in Saudi Arabia. A forecast of a high quality health care. AB - OBJECTIVES: To explore the current structure of the Saudi health care system, and assess the quality of health care in the Kingdom of Saudi Arabia (KSA) based on the indicators provided by the Institute of Medicine (IOM), and to provide recommendations for improvements. METHODS: This study explores the current structure of the Saudi health care system using a systematic review of studies published between 2009 and 2013. The IOM indicators of quality health care (safe, effective, patient-centered, timely, efficient, and equitable) are used to determine the current quality of healthcare in KSA. Studies that examined the quality of health care were evaluated for methodological soundness by giving a quality score based on Russell and Gregory's criteria. RESULTS: The quality of healthcare in KSA has progressed significantly over the recent years at all levels of health services. Like many countries, KSA is investing money and efforts to improve quality of healthcare in the Kingdom. Although significant progress has been made, barriers affecting this quality are still apparent as the general population increases, patients' health care needs, and demands are also rising. Factors affecting the quality of healthcare can be categorized into patient factors (such as health literacy, access to care, and culture), and providers' factors (including medical care, workload, culture, and job satisfaction). CONCLUSION: As a result of these unaddressed issues, the quality of healthcare in the Kingdom may be degenerating. Additionally, as the population of KSA has increased and medical technology has become more sophisticated and costly, and patients' demands and expectations have also increased. Providing quality healthcare to all patients is a fundamental human right. Poor quality healthcare causes patient suffering, institutional waste, and misuse of community resources. PMID- 25129178 TI - Cytotoxic effect of Salvadora persica extracts on human gingival fibroblast cells. AB - OBJECTIVES: To assess the cytotoxic potential of Salvadora persica (S. persica) extracts on human gingival fibroblast (HGF) cells. METHODS: This study was conducted between January and May 2012 in collaboration with Dental Caries Research Chair, College of Dentistry, King Saud University, Riyadh, Saudi Arabia. Extracts of S. persica using hexane, ethylacetate, and ethanol as solvents at concentrations of 0.5 mg/ml and 1 mg/ml were evaluated for their cytotoxic activity against HGFs using the 3 cytotoxic assays: (3-(4,5-Dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide, a tetrazole) (MTS), lactic dehydrogenase (LDH), and crystal violet (CV). International standards for the evaluation of medical materials recommended cut-off value of cell survival >70% was used for interpretation of the results. RESULTS: Ethanol extract of S. persica at 0.5 mg/ml and 1 mg/ml and hexane extract of S. persica at 0.5 mg/ml were completely devoid of cytotoxic activity, hexane extract at 1 mg/ml in comparison with controls demonstrated some cytotoxicity with cell survival of 88% (p=0.045) in MTS, 86% (p=0.01) in LDH, and 88% (p=0.002) in CV assays. Similarly, ethyl acetate extract of S. persica at 0.5 mg/ml maintained cell viability of 91% in MTS, 81% in LDH, and 80% in CV assays. Maximum cytotoxicity against HGFs was observed with ethyl acetate extract of S. persica at 1 mg/ml with cell survival of 60% in MTS, 40% in LDH, and 66% CV assays (p=0.0001). CONCLUSION: The acceptable level of cytotoxicity associated with S. persica ethanol and hexane extracts requires further evaluation to be used as irrigation solutions in endodontic treatment. PMID- 25129179 TI - Diagnostic clues for spondylitis in acute brucellosis. AB - OBJECTIVES: To determine the diagnostic factors for brucellar spondylitis. METHODS: This retrospective study included 227 consecutive brucellosis patients admitted to the Infectious Diseases and Clinical Microbiology clinics of Adiyaman State Hospital and Adiyaman 82 nd Year State Hospital, Adiyaman, Turkey between January 2010 and December 2012. Acute brucellosis was diagnosed by standard tube agglutination test and/or growth of Brucella spp. in appropriately prepared culture media (Bactec). Brucellar spondylitis was diagnosed and followed-up with contrast-enhanced magnetic resonance imaging. RESULTS: Among the 227 brucellosis patients included, 88 (38.8%) were male, and 139 (61.2%) were female. Brucellar spondylitis was detected in 54 patients (23.7%). Brucellar spondylitis patients had higher mean age, higher fever, and higher blood culture positivity rate when compared with brucellosis patients (p=0.001, p=0.001, and p=0.001). Logistical regression analysis determined that male gender (OR: 3.006), older age (OR: 1.025), erythrocyte sedimentation rate (ESR) (OR: 1.067), high fever at the time of admission (OR: 2.550), and positive blood cultures for Brucella spp. (OR: 4.003) values were independently associated with brucellar spondylitis. However, high C-reactive protein (CRP) levels (OR: 0.971) were not found as a risk factor for brucellar spondylitis. CONCLUSIONS: The results of this study shows that the risk of developing brucellar spondylitis is high in patients with acute brucellosis, who are at advanced age, who have high fever, that have Brucella spp. growth in their blood culture that has a high ESR value, and who are male. PMID- 25129180 TI - Ten-year review of invasive Candida infections in a tertiary care center in Saudi Arabia. AB - OBJECTIVES: To review the epidemiology of invasive Candida infections in a single center in Saudi Arabia over a subsequent 10-year period. METHODS: This retrospective study was carried out in a single center in Saudi Arabia over a 10 year period. Records of all patients with invasive Candida infections (ICI) over the period from January 2003 to December 2012 were reviewed. Mann-Whitney U test was used for comparison of Candida albicans (C. albicans) versus non-albicans Candida species, and fluconazole resistance versus fluconazole susceptible in relation to crude mortality at 30 days and 90 days. RESULTS: Eight hundred positive sterile site cultures, associated with 652 ICI were identified. Median age was 52 years and 53% of patients were males. Candida albicans were the most common species (38.7%), followed by Candida tropicalis (18.9%), and Candida glabrata (C. glabrata) (16.3%). The proportion of ICI caused by C. albicans remained stable over time (p=0.07), but C. glabrata increased significantly (p<0.001). The median rate of ICI per 1,000 hospital discharges per year was 1.65, with a significant trend towards higher rates over time (p=0.01). Most isolates were susceptible to fluconazole, voriconazole, and amphotericin B. Only 66.7% of Candida krusei were susceptible to caspofungin. Overall 30-day crude mortality was 40.6%. There was no significant difference in crude mortality in association with C. albicans compared with non-albicans species, nor in association with fluconazole resistance. CONCLUSION: The rate of ICI increased significantly in the proportion of ICI caused by C. glabrata. Most isolates remain susceptible to caspofungin, voriconazole, and amphotericin B. The crude mortality remains high. PMID- 25129181 TI - Quality of life assessment using the World Health Organization quality questionnaire pre- and post- otolaryngological surgery among patients in western Saudi Arabia. AB - OBJECTIVES: To evaluate the health-related quality of life (HRQoL) of patients' pre- and post- otolaryngological surgery. METHODS: We conducted a cross-sectional study of patients who underwent otolaryngological surgery in the western region of Saudi Arabia between March and October 2013. We administered the Arabic version of the World Health Organization Quality of Life assessment instrument to all patients before surgery and 2-4 weeks after surgery. The demographic details such as age, gender, level of education, marital status, patients' incomes, otolaryngology diagnosis, and type of otolaryngology surgery were analyzed. RESULTS: A total of 99 patients (43 males and 52 females), ranging from 1-75 years of age (mean: 21.6 years), were included in this study. The most frequently diagnosed conditions were chronic tonsillitis and obstructive sleep apnea due to adenoid enlargement. Adenotonsillectomy was the most frequently performed surgery, followed by septoplasty and myringotomy with grommet tube insertion. For all domains, patients had significantly higher scores post-surgery. The highest score was obtained for the social relationship domain and the lowest for the physical health domain. However, the highest differences between the pre- and post- surgery scores were for physical health (7.9), psychological (5.1), environmental (2.5), and social health (2.3) domains. CONCLUSION: The HRQoL of patients improved significantly after otolaryngology surgery. PMID- 25129182 TI - Risk factors for posterior to right recurrent laryngeal nerve lymph node metastasis in papillary thyroid carcinoma. AB - OBJECTIVES: To identify the risk factors for posterior right recurrent laryngeal nerve lymph node metastasis (PRRLN-LNM) in papillary thyroid carcinoma (PTC). METHODS: We conducted a retrospective study of 389 patients with primary PTC who underwent right lobectomy or total thyroidectomy, and comprehensive right or bilateral central compartment dissection (CCD) with or without lateral neck dissection (LND) between January 2010 and May 2013 at the Department of Head and Neck Surgery, Institute of Micro-Invasive Surgery of Zhejiang University, Zhejiang, China. The clinicopathological findings were investigated, and relative risk factors for PRRLN-LNM were analyzed. RESULTS: Central compartment LNM were present in 50.9% (198/389), and PRRLN-LNM were present in 12.6% (49/389) of patients, wherein 3.1% (12/389) had PRRLN-LNM only. A multivariate analysis revealed that younger age (<= 35 years), extrathyroidal extension (ETE), lateral compartment LNM, prelaryngeal LNM, pretracheal, and right paratracheal LNM were independent predictors of PRRLN-LNM. CONCLUSION: This study revealed that younger age (<= 35 years), ETE, prelaryngeal LNM, lateral compartment LNM, and pretracheal and right paratracheal lymph nodes (anterior to the right recurrent laryngeal nerve [level VIa]), LNM were independent factors of PRRLN-LN (level VIb). Therefore, comprehensive right CCD should be routinely performed for such patients. PMID- 25129183 TI - Clinical outcomes of transradial unprotected left main coronary artery stenting in the elderly. AB - OBJECTIVES: To evaluate the long-term results in elderly patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents for unprotected left main coronary artery disease by transradial approach. METHODS: This study took place in Qinhuangdao First Hospital, Hebei Medical University, Hebei, China between October 2006 and December 2009. Seventy-nine elderly patients with unprotected left main coronary artery (ULMCA) stenosis, aged >70 years, that underwent drug-eluting stent were evaluated. The occurrence of major adverse cardiac events (MACE) (death, non-fatal myocardial infarction, stroke or target lesion revascularizations) was recorded after 3 years of follow-up. RESULTS: After 3 years follow-up, the MACE free survival rate was 72.2%. Cardiac deaths occurred in 7.6% of patients. Myocardial infarction occurred in 5.1%, and target lesion revascularization in 13.9% of patients. Age and left main distal bifurcation were favorable predictors of MACE. CONCLUSIONS: Percutaneous coronary intervention can be performed with good angiographic and clinical results through a transradial approach in the elderly. The long term survival suggests that PCI in ULMCA patients >= 70 years is safe and efficacious. PMID- 25129184 TI - External cephalic version for breech presentation at term. A prospective interventional study. AB - OBJECTIVES: To evaluate the external cephalic version (ECV) procedure for the management of at term breech presenting fetuses. METHODS: In this prospective, interventional study, 90 patients with uncomplicated breech presentations at or after 37 weeks' gestation were considered for ECV. This was performed in Al Batool Teaching Hospital, Mosul, Iraq, between January 2011 and March 2012. The main outcome measure was assessed as the success rate of ECV attempt and the rate of cesarean section following a successful procedure. Parity, type of breech, placental location, and birth weight were evaluated as predictors of success. Also, any fetal or maternal complications during the procedure were evaluated. Data were analyzed by x2 test. Statistical significance was determined at a level of p<0.05. RESULTS: The success rate was 80%. The rate of cesarean section following successful procedure was only 12.5%. Prognostic parameters associated with successful ECV were multiparity and flexed type of breech. There were no serious fetal or maternal complications associated with the attempt. CONCLUSIONS: With appropriate selection of patients, ECV is highly successful and is a safer alternative to vaginal breech delivery or cesarean delivery. PMID- 25129185 TI - Skeletal and dental characteristics of subjects with incompetent lips. AB - OBJECTIVES: To evaluate the cephalometric features of subjects with incompetent lips, and to find the most discriminant variables for lip incompetence among the following: dental protrusion and proclination, antero-posterior and vertical skeletal relationships, and lip dimensions. METHODS: This retrospective study was conducted at King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between 2011 and 2012. Cephalograms of 84 subjects (22 males and 62 females, aged 20.18+/ 3.65 years) diagnosed as having incompetent lips were collected (incompetent group [IG]) and compared with the control group (CG), matching in age and gender distribution. Thirty-five measurements were compared between the 2 groups using independent t-test. Stepwise discriminant analysis of lip incompetence was performed. RESULTS: Compared to the CG, subjects in the IG had thinner upper lips, shorter upper and lower lips, more retrognathic facial types, greater angle between nasion-point A and nasion-point B, shorter anterior and posterior cranial bases, shorter palatal length, shorter mandibular body length, shorter ramal length, steeper mandibular plane, less prominent chin, bimaxillary dental protrusion, and smaller inter-incisal angle. The significant discriminant variables, in order, were inter-incisor angle, inclination of upper incisors, ramal height, anterior cranial base, palatal plane to Frankfort horizontal plane angle, lower and then upper anterior dental height, upper lip thickness, and length. CONCLUSIONS: The presence of incompetent lips can be attributed to more than one factor and not only bimaxillary protrusion. This should be considered during the treatment planning of such problem. PMID- 25129186 TI - A cross sectional study on the acceptance of pre-hospital continuous positive airway pressure ventilation among ambulance paramedic in an urban emergency medical service system in a developing country. AB - OBJECTIVES: To assess the acceptance among the developing country urban paramedics towards pre-hospital continuous positive airway pressure (CPAP) ventilation. METHODS: A cross-sectional prospective study was conducted among the ambulance paramedics working at the pre-hospital care unit of the Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia from March 2012 to August 2012 on ambulance paramedics. Questionnaires were used to assess their experience, knowledge, and perception, while their competencies were assessed using an Objective Structured Clinical Examination by 2 independent-calibrated raters on the use of the Boussignac CPAP system. RESULTS: Twenty-six ambulance paramedics qualified for this study with an average work experience of 5.59+/ 3.53 years. A total of 76.9% had no formal training for CPAP during their study years. Knowledge of CPAP apparatus-arrangement sequence scored as 88.5% correct, while 96.2% scored 'Good' to 'Very-good' in the ability to diagnose conditions that warrant its use. A total of 76.9% were confident to monitor patients on CPAP, and 61.5% in applying the device. However, only 53.8% were confident to start the CPAP, and 38.5% to troubleshoot if any problem arose. For perceptions, 96.2% felt it was easy to learn CPAP, while 88.5% felt that paramedics could use it without supervision, and 80.8% felt that it should not be confined to the Emergency Department setting. A total of 96.1% were competent in CPAP application. CONCLUSION: Developing country urban ambulance paramedics possessed adequate knowledge, positive attitudes, and demonstrated good CPAP application skills. However, lack of confidence towards decision to initiate and troubleshoot of potential complications were the main obstacles hindering its use. PMID- 25129187 TI - Acute hemiplegia as a rare presentation of infantile Guillain-Barre syndrome. AB - Guillain-Barre syndrome (GBS) usually presents in a symmetrical ascending fashion of weakness. We present a 6-month-old male infant who presented to our emergency room with acute left-sided limb weakness and head lag 3 days after a febrile upper respiratory tract infection. A diagnosis of GBS was established by confirming high cerebrospinal fluid protein, motor nerve reduced amplitude, and prolonged conductions, and MRI T2 high signal intensity affecting the ventral roots of the spinal cord. He showed remarkable clinical and neurophysiological improvement after intravenous immunoglobulin and intensive physiotherapy. The occurrence of infantile acute hemiplegia as a presentation of GBS is rare. This report highlights the importance of considering GBS in the differential diagnosis so that early effective treatment may be started. PMID- 25129188 TI - Toe tourniquet syndrome. AB - Toe tourniquet syndrome refers to external, mechanical, circumferential constriction of the toes. We report a series of 4 infants with toe tourniquet syndrome from Saudi Arabia who presented during wintertime with very similar symptoms (approximately 48 hours of inconsolable crying and irritability), similar involved region (toes), and similar constricting agent (hairs). Immediate removal of the hair fibers was carried out in all patients, fortunately followed by fast healing with no signs of tissue necrosis. The prompt diagnosis and treatment of the condition were vital in attaining the good outcome and preventing ischemic complications. PMID- 25129189 TI - Colon cancer metastasis to the thyroid gland. AB - Thyroid metastasis originating from colon cancer is an uncommon clinical entity. We present a case of a 40-year-old Saudi male patient that was known to have metastatic adenocarcinoma of the colon, and who presented initially with hoarseness of voice. A left thyroid lesion was found and fine-needle aspiration biopsy showed that it was a colon cancer metastasis. His condition later deteriorated with development of stridor. Tracheostomy was performed and the diagnosis was confirmed by biopsy. A high index of suspicion is required to consider colorectal carcinoma metastatic to the thyroid. PMID- 25129190 TI - Minimally invasive endoscopic removal of a massive trabecular juvenile ossifying fibroma of the paranasal sinuses. AB - An 11-year-old female patient presented with left-sided nasal obstruction and upward displacement of the left eye of 3 months duration. Clinical examination revealed a firm mass in the left nasal cavity. A CT scan showed a massive tumor involving the left maxillary sinus with extension into the ethmoid sinus, and encroaching on the left orbit. Histopathological examination revealed trabecular juvenile ossifying fibroma, which was removed via a transnasal endoscopic surgery by the Otorhinolaryngology, Head and Neck and the skull base team. She tolerated the lengthy procedure well, and there was no recurrence postoperatively as the tumor was resected completely. There was no external scarring and no psychological trauma discerned. PMID- 25129191 TI - Nasal chondromesenchymal hamartoma in an adolescent with pleuropulmonary blastoma. AB - Nasal chondromesenchymal hamartoma (NCMH) is an extremely rare benign lesion arising in the sino-nasal tract. They usually affect children below one year of age. The pathogenesis of these lesions is poorly understood however, they have been associated with pleuropulmonary blastoma (PPB). Although benign, malignant transformation has been reported in the literature. On literature review, we found 32 reported cases, most of them occurring in children below one year. We report a 14-year-old adolescent male with history of PPB at the age of 6, presenting with bilateral nasal obstruction and decreased sense of smell. In our case report we highlight the association between PPB and NCMH, and describe an unusual presentation. PMID- 25129192 TI - Direct digital radiograph. Technicians role in obtaining good images. AB - OBJECTIVES: To determine the rejected rate of direct digital radiography (DRs) in our hospital, benchmark it with other institutes, and explore the causes of rejection. METHODS: Data were collected between June 2012 and May 2013 at King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. The rejected analysis was registered in the system, which is a built in software. Reasons for rejection could not be deleted, and no further imaging is allowed for the same patient without reporting the reason for rejection. Reasons for rejection are predefined by the machine. RESULTS: Of 89,797 images that were acquired, 13,371 were rejected, with a rejection rate of 15%. Positioning errors were the main reason for rejection, followed by artifact 28.5%, and motion 17.1%. As for body parts pelvis, abdomen, spine, and knee were recorded as rejected with higher rates than the average. CONCLUSION: This study has shown a number of unnecessary repeated imaging of patients. In addition, reject analysis in DR is proven to be an indicator for quality in imaging, the reasons of rejection that have high percentage for occurrence should be given more focus during patients scan. PMID- 25129193 TI - Quality of life among adults with beta-thalassemia major in western Saudi Arabia. AB - OBJECTIVES: To assess the quality of life in the thalassemia adult patients and clarify how effective the management is of these patients and whether a change in care is warranted. METHODS: In this cross-sectional study, adult thalassemia patients (>18 years) of both genders, attending the day care unit in King Abdulaziz University Hospital, Jeedah, Saudi Arabia were surveyed using SF-36 questionnaire. Data were collected between October 2012 and December 2012. The questions highlighted 3 health status scales; physical functioning (PF), emotional functioning (EF), and social functioning (SF). Scores were analyzed using SPSS. RESULTS: Forty-eight adults were surveyed (mean+/-SD: 26.02+/-5.56). These were made up of 60.4% males and 41.7% were Saudis. The frequency of blood transfusion was every 3 weeks in 81.3% of patients, but 18.8% were having transfusions less frequently. Half of our sampled patients were splenectomized (54.2%). The PF score for the total sample was 61.4 (SD=22.7), the SF score was 75 (SD=26.4) and the EF score was 69.7 (SD= 21.6); the SF and EF scores were lower in females and non-Saudis compared to male Saudis. CONCLUSION: The PF score in our sample was low compared to other regional studies; the SF and EF scores were low in females and non-Saudis. PMID- 25129194 TI - Effects of hyperandrogenism and high body mass index on acne severity in women. AB - OBJECTIVES: To determine the association between hyperandrogenism and obesity with acne, and correlation between the severity of acne with the clinical and laboratory parameters of hyperandrogenism. METHODS: One hundred and forty-one female with acne vulgaris and 73 healthy women were included in this study. The correlation of clinical and laboratory signs of hyperandrogenism and the severity of acne was examined. RESULTS: The prevalence of overweight and obese individuals in the group with acne was determined significantly higher than the control group. There was a positive correlation between body mass index (BMI) value and the severity of acne. The frequency of hirsutism, menstrual irregularity, androgenetic alopecia, seborrhea and polycystic ovary in the group with acne were found significantly higher than the control group. The average levels of free testosterone (fT), total testosterone (TT), dehydroepiandrosteron sulfate, and prolactine in the groups with acne were found significantly higher compared with the control group. There was a positive correlation between the fT and TT levels and the severity of acne. CONCLUSION: The prevalence of hyperandrogenism and obesity was increased in women with acne. According to the results of our study, it can be said that circulating androgen levels and BMI play a key role in the severity of acne. PMID- 25129195 TI - Unconventional materials and substances used in water pipe (narghile) by smokers in central western region of Saudi Arabia. AB - OBJECTIVES: To investigate the use of unconventional substances and materials in water pipe among cafe water pipe smokers. METHODS: This was a questionnaire-based survey among subjects attending coffee shops in the region of Al Madinah, Saudi Arabia between February and March 2013. RESULTS: We invited 110 subjects, only 90 consented to participate in the study. A percentage of 1.1% used fluids other than water in the water pipe tank, 18.9% added other soft drinks to the tank, and 7.8% added flowers, spices or drugs to the tobacco mix placed in the head of the water pipe. A proportion of participants used fruits to replace the water pipe head (12.2%), or to replace water pipe tank (4.4%). Higher number of children the smokers had and cafe smoking were all significantly associated with unconventional practices. CONCLUSION: A substantial percentage of sample of water pipe smokers in Al Madinah, Saudi Arabia use unusual materials and/or substances in the water pipe and this is probably encouraged by cafe smoking. PMID- 25129196 TI - Umbilical neoplasm as the first sign of pancreatic adenocarcinoma. PMID- 25129197 TI - Infection prevention and control guidelines for patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. PMID- 25129198 TI - Timing of dental development in Saudi cleft lip and palate patients. PMID- 25129199 TI - Asthma drugs suppress growth. PMID- 25129200 TI - Longitudinal trajectories of aberrant behavior in fragile X syndrome. AB - The Aberrant Behavior Checklist-Community (ABC-C; Aman et al., 1995) has been increasingly adopted as a primary tool for measuring behavioral change in clinical trials for individuals with fragile X syndrome (FXS). To our knowledge, however, no study has documented the longitudinal trajectory of aberrant behaviors in individuals with FXS using the ABC-C. As part of a larger longitudinal study, we examined scores obtained on the ABC-C subscales for 124 children and adolescents (64 males, 60 females) with FXS who had two or more assessments (average interval between assessments was approximately 4 years). Concomitant changes in age-equivalent scores on the Vineland Adaptive Behavior Scales (VABS) were also examined. As expected for an X-linked genetic disorder, males with FXS obtained significantly higher scores on all subscales of the ABC-C and significantly lower age-equivalent scores on the VABS than females with FXS. In both males and females with FXS, scores on the Irritability/Agitation and Hyperactivity/Noncompliance subscales of the ABC-C decreased significantly with age, with little to no change occurring over time on the Lethargy/Social Withdrawal, Stereotypic Behavior, and Inappropriate Speech subscales. The decrease in scores on the Hyperactivity/Noncompliance domain was significantly greater for males than for females. In both males and females, age-equivalent scores on the VABS increased significantly over this developmental period. These results establish a basis upon which to evaluate long-term outcomes from intervention-based research. However, longitudinal direct observational studies are needed to establish whether the severity of problem behavior actually decreases over time in this population. PMID- 25129202 TI - Patterns of habitual physical activity in youth with and without Prader-Willi Syndrome. AB - Children classified as overweight or obese and those with disabilities are at a greater risk of not meeting the minimum recommendation of 60 min a day of moderate to vigorous physical activity (PA). Youth with Prader-Willi Syndrome (PWS) appear to participate in less PA compared to nonsyndromal children, likely due to syndrome-related factors. However, description of PA patterns in youth with PWS is lacking. The purpose of this study was to characterize PA in youth with PWS and to compare it to PA in children with nonsyndromal obesity. Twenty four youth with PWS (ages 8-16 years) and 40 obese children without PWS (OB) (ages 8-11 years) wore accelerometers for eight consecutive days. Data were screened for compliance and classified into PA intensities: sedentary behavior (SED), light (LPA), moderate (MPA), vigorous (VPA) and moderate plus vigorous (MVPA). Youth with PWS spent 19.4% less time in weekly LPA (p=0.007) and 29.8% less time in weekly VPA compared to OB controls (p=0.036). All other intensities were similar between groups. In addition, PWS participated in less LPA and VPA during the weekends compared to OB, and less LPA on weekdays when compared to OB. There was also a trend towards PWS participating in less MVPA during the weekends and less VPA during the weekends than OB controls. There was a trend towards PWS participating in less VPA on weekends compared to weekdays, while OB participated similarly in VPA on weekdays and weekend days. On average, neither PWS nor OB children met minimum MVPA recommendations. The results suggest there is a need to design exercise programs for PWS youth that focus on integrating vigorous intensity activities, especially during the weekends when structured PA may not be available. PMID- 25129201 TI - Prevalence and factors associated with polypharmacy in Victorian adults with intellectual disability. AB - Although polypharmacy is a medication safety concern leading to increased risk of non-adherence, adverse drug reaction and drug-drug interactions, polypharmacy and associated risk factors has rarely been investigated involving people with ID at a population level. The purpose of this paper is to analyze the prevalence of polypharmacy and to evaluate the role of different factors associated with polypharmacy in a state-wide representative population of adults with ID. In a population-based survey in Victoria, Australia, 897 people with ID 18 years of age or older were selected by simple random sampling. The data were collected from proxy respondents on behalf of people with ID. Polypharmacy was defined as the concomitant use of five or more medications. The data were weighted to reflect the age/sex/geographic distribution of the population. Results revealed that more than 76% of adults with ID had used prescribed medicine and about 21% were exposed to polypharmacy in the last two weeks. In both univariate and multivariate analyses, polypharmacy was significantly associated with older age, unemployment and inability to get help from family and friends if needed. After controlling for age, sex and severity of intellectual disability, polypharmacy was associated with having a blood pressure, blood cholesterol and blood glucose level check. Polypharmacy was also associated with a greater number of visits to general practitioners, fair or poor reported health status and inability to walk unaided. Subjects with epilepsy, diabetes, stroke, osteoporosis and cancer had a higher probability of polypharmacy. None of the disease inducing behaviors was associated with polypharmacy. This study highlights the need that medication should be regularly reviewed overall in ID population and particularly when polypharmacy exists. PMID- 25129203 TI - Glomerular nestin expression: possible predictor of outcome of focal segmental glomerulosclerosis in children. AB - BACKGROUND: A high prevalence of chronic kidney disease among children with focal segmental glomerulosclerosis (FSGS) leads to a permanent quest for good predictors of kidney dysfunction. Thus, we carried out a retrospective cohort study in order to examine known clinical and morphological predictors of adverse outcome, as well as to investigate glomerular nestin expression as a potential new early predictor of kidney dysfunction in children with FSGS. Relationships between nestin expression and clinical and morphological findings were also investigated. METHODS: Among 649 renal biopsy samples, obtained from two children's hospitals, FSGS was diagnosed in 60 children. Thirty-eight patients, who met the criteria for this study, were followed up for 9.0 +/- 5.2 years. Using Kaplan-Meier and Cox's regression analysis, potential clinical and morphological predictors were applied in two models of prediction: after disease onset and after the biopsy. RESULTS: The present study revealed the following significant predictors of kidney dysfunction: patients' ages at disease onset, as well as age at biopsy, resistance to corticosteroid treatment, serum creatinine level, urine protein/creatinine ratio, vascular involvement, tubular atrophy, interstitial fibrosis, and decreased glomerular nestin expression. CONCLUSIONS: The most important finding of our study is that nestin can be used as a potential new early morphological predictor of kidney dysfunction in childhood onset of FSGS, since nestin has been obviously decreased in both sclerotic and normal glomeruli seen by light microscopy. PMID- 25129204 TI - Serum suPAR levels are modulated by immunosuppressive therapy of minimal change nephrotic syndrome. AB - BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) could be a causative factor in idiopathic focal segmental glomerulosclerosis (FSGS). It is currently unknown to what extent suPAR levels could be affected by treatment with immunosuppressive drugs such as cyclosporin A (CsA) and mycophenolate mofetil (MMF). Treatment with CsA, but not MMF, is accompanied by nephrotoxicity, and since suPAR levels correlate with glomerular filtration rate (GFR), treatment with these drugs could indirectly modulate suPAR levels by their effect on renal function. METHODS: We measured suPAR levels in a recent prospective multicenter crossover trial comparing the efficacy of MMF and CsA in pediatric patients with minimal change disease (MCD) and frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). All patients had biopsy-proven MCD and normal renal function; they were treated with each drug for 1 year in a crossover study design. Serum suPAR levels were measured before and after 1 year of therapy with MMF (n = 40) and CsA (n = 35). RESULTS: The suPAR levels decreased after 1 year of treatment with MMF (p < 0.05). Conversely, suPAR levels increased after 1 year of treatment with CsA in the same patients (p = 0.01). These changes in suPAR levels were not correlated to the estimated glomerular filtration rate (eGFR) or changes in the GFR. CONCLUSIONS: Data from this prospective randomized trial suggest that treatment with MMF and CsA is associated with different effects on suPAR levels in children with MCD and that these are independent of their effects on GFR. PMID- 25129205 TI - Central venous catheterization using a perfused human cadaveric model: application to surgical education. AB - OBJECTIVE: The purpose of this article is to present a unique training model using a perfused human cadaver for central line placement training with the ultimate goal of reducing central venous catheter mechanical complications. DESIGN: The applicability of the fresh tissue cadaver model for central line placement was assessed using a 10-item questionnaire with a 5-point Likert-type scale. Respondents were asked to rate their opinions as strongly agree, agree, neutral, disagree, or strongly disagree. SETTING: All participants received a didactic lecture followed by supervised practice on a commercially available simulator. The students were then relocated to the Fresh Tissue Dissection Laboratory where they practiced central vein catheterization on a fresh perfused human cadaver. PARTICIPANTS: Course participants included 87 physicians from various medical specialties at different stages of training. RESULTS: Results of the survey demonstrated that 91% of the participating physicians found the perfused cadaveric model to be a true simulation of conditions that exist in live patients, and 98% reported that the use of this model promoted acquisition of technical skills. CONCLUSION: The integration of central line placement training on perfused cadavers into residency and fellowship training provides an unparalleled realistic simulation to participants. Further study is needed to assess whether realistic simulation translates into objective end points such as decreased mechanical complications. PMID- 25129206 TI - Post-mortem 7.0-tesla magnetic resonance study of cortical microinfarcts in neurodegenerative diseases and vascular dementia with neuropathological correlates. AB - BACKGROUND: Until recently cortical microinfarcts (CMIs) were considered as the invisible lesions in clinical-radiological correlation studies that rely on conventional structural magnetic resonance imaging. The present study investigates the presence of CMIs on 7.0-T magnetic resonance imaging (MRI) in post-mortem brains with different neurodegenerative and cerebrovascular diseases. MATERIALS AND METHODS: One hundred-seventy five post-mortem brains, composed of 37 with pure Alzheimer's disease (AD), 12 with AD associated to cerebral amyloid angiopathy (AD-CAA), 38 with frontotemporal lobar degeneration, 12 with amyotrophic lateral sclerosis, 16 with Lewy body disease (LBD), 21 with progressive supranuclear palsy, 18 with vascular dementia (VaD) and 21 controls were examined. According to their size several types of CMIs were detected on 3 coronal sections of a cerebral hemisphere with 7.0-T MRI and compared to the mean CMI load observed on histological examination of one standard separate coronal section of a cerebral hemisphere at the level of the mamillary body. RESULTS: Overall CMIs were significantly prevalent in those brains with neurodegenerative and cerebrovascular diseases associated to CAA compared to those without CAA. VaD, AD-CAA and LBD brains had significantly more CMIs compared to the controls. While all types of CMIs were increased in VaD and AD-CAA brains, a predominance of the smallest ones was observed in the LBD brains. CONCLUSIONS: The present study shows that 7.0-T MRI allows the detection of several types of MICs and their contribution to the cognitive decline in different neurodegenerative and cerebrovascular diseases. PMID- 25129207 TI - Extrathymic malignancies in a defined cohort of patients with myasthenia gravis. AB - INTRODUCTION: Myasthenia gravis (MG) may be associated with extrathymic malignancies, especially in patients with thymoma. AIM: To determine the frequency and type of extrathymic malignancies in MG patients from the Belgrade area, and to identify potential risk factors associated with tumors. PATIENTS AND METHOD: The study comprised 390 patients with MG. Different sociodemographic and clinical variables potentially associated with extrathymic neoplasms were analyzed. RESULTS: Extrathymic malignancies were present in 42 (10.8%) MG patients - 22 (52.4%) males and 20 (47.6%) females. The most frequently detected were breast (40%) and lung (40%) neoplasms. The tumors appeared with similar frequency before (45.2%) and after the onset of MG (42.9%). Significant predictors for the development of extrathymic malignancies were current age (p = 0.001) and immunoglobulin (IVIg) therapy (p = 0.021). On the other hand, current age (p=0.001), longer MG duration (p = 0.001) and generalized form of MG (p = 0.002) were significant predictors of malignancy occurring after the MG onset. CONCLUSION: Our study revealed that older MG patients, as well as those with longer duration of the disease, and those who received IVIg therapy had a higher oncogenic risk for the development of extrathymic malignancies. PMID- 25129209 TI - Letter from the guest editors. PMID- 25129210 TI - Dose tracking and dose auditing in a comprehensive computed tomography dose reduction program. AB - Implementation of a comprehensive computed tomography (CT) radiation dose reduction program is a complex undertaking, requiring an assessment of baseline doses, an understanding of dose-saving techniques, and an ongoing appraisal of results. We describe the role of dose tracking in planning and executing a dose reduction program and discuss the use of the American College of Radiology CT Dose Index Registry at our institution. We review the basics of dose-related CT scan parameters, the components of the dose report, and the dose-reduction techniques, showing how an understanding of each technique is important in effective auditing of "outlier" doses identified by dose tracking. PMID- 25129208 TI - Curcumin improves the integrity of blood-spinal cord barrier after compressive spinal cord injury in rats. AB - Previous studies have shown that curcumin (Cur) can produce potent neuroprotective effects against damage due to spinal cord injury (SCI). However, whether Cur can preserve the function of the blood-spinal cord barrier (BSCB) is unclear. The present study was performed to investigate the mechanism underlying BSCB permeability changes, which were induced by treatment with Cur (75, 150, and 300 mg/kg, i.p.) after compressive SCI in rats. BSCB permeability was evaluated by Evans blue leakage. Motor recovery of rats with SCI was assessed using the Basso, Beattie, and Bresnahan scoring system every day until the 21st days post injury. The protein levels of heme oxygenase-1 (HO-1), tight junction protein, and inflammatory factors were analyzed by western blots. The expression of the inflammatory factors tumor necrosis factor-alpha (TNF-alpha) and nuclear factor kappaB (NF-kappaB) mRNA was determined with reverse transcription-polymerase chain reactions. Treatment with Cur (150 and 300 mg/kg) significantly reduced Evans blue leakage into the spinal cord tissue at 24h after SCI. Cur (150 mg/kg) significantly increased HO-1 protein expression. The levels of TNF-alpha and NF kappaB mRNA and protein greatly increased at 24h after SCI, and this increase was significantly attenuated by Cur treatment. ZO-1 and occludin expression was upregulated by Cur (150 mg/kg) treatment after SCI, and this effect was blocked by the HO-1 inhibitor zinc protoporphyrin. Long-term effects of Cur on motor recovery after SCI were observed. Our results indicated that Cur can improve motor function after SCI, which could correlate with improvements in BSCB integrity. PMID- 25129211 TI - Magnetic resonance enterography in evaluation and management of children with Crohn's disease. AB - The role of radiologic evaluation in Crohn's disease (CD) has undergone a recent paradigm shift in which the radiologist adds value to the multidisciplinary team by longitudinally assessing therapeutic response and identifying treatment modifying subtypes, such as fibrostenotic or fistulizing disease. Magnetic resonance enterography (MRE) has become the primary imaging modality used. The combination of multiplanar, multiparametric, and multiphasic contrast-enhanced imaging with the high spatial resolution and very high tissue contrast of MR imaging allows for detailed evaluation of intra-abdominal pathology, without the risk of cumulative radiation exposure. MRE provides the benefit of a complete evaluation of mural, extramural, and even extraintestinal manifestations and complications of CD in a single examination. Cine motility sequences and diffusion-weighted imaging may further increase sensitivity and specificity. MRE represents an ideal imaging modality for initial evaluation, assessment of therapeutic response, and evaluation of complications in patients with CD. PMID- 25129212 TI - Neonatal neurosonography. AB - Neonatal neurosonography is used commonly to evaluate the central nervous system in the neonatal intensive care setting. The procedure can be performed at the bedside in these critically ill patients who may suffer from hemodynamic and thermoregulatory instability and often require mechanical ventilation. This article reviews current recommendations regarding neurosonography technique, pathophysiology, and imaging of intracranial insults including hemorrhage, white matter injury, infarction, and hypoxic-ischemic encephalopathy. PMID- 25129213 TI - Techniques that decrease or eliminate ionizing radiation for evaluation of ventricular shunts in children with hydrocephalus. AB - Shunted hydrocephalus in children is a commonly seen diagnosis in hospitals throughout the world and is one of the most common chronic pediatric neurosurgical conditions. These children undergo numerous studies for routine surveillance as well as for evaluation of shunt malfunction, many of which are associated with significant radiation exposure over the child's lifetime. It is in the child's best interest to minimize the overall exposure to ionizing radiation so as to decrease the chance of the deleterious effects from occurring. The article outlines the epidemiology of ventricular shunt catheters, the typical indications and methods for shunt evaluation, and the preferred alternative imaging methods that eliminate or reduce radiation exposure. PMID- 25129214 TI - Pectus excavatum: current imaging techniques and opportunities for dose reduction. AB - Pectus excavatum (PE) is the most common congenital chest wall deformity in children. It affects 1 in every 300-1000 live births with a male to female ratio of 5:1. Most of the patients present in their first year of life. During the teenage years, patients may have exercise intolerance and psychological strain because of their chest wall deformity. The Nuss and Ravitch procedures are established methods of surgical correction of PE. An index of severity known best as the Haller index, typically evaluated with computed tomography scan, when measuring greater than 3.2 is considered to indicate moderate or severe PE and is a prerequisite for third-party insurance reimbursement for these corrective procedures. This article reviews the clinical features of PE, the role of imaging, and the opportunities for radiation dose reduction. PMID- 25129215 TI - Primary liver tumors in pediatric patients: proper imaging technique for diagnosis and staging. AB - Liver tumors in children are rare and comprise a diverse set of both benign and malignant lesions, most of which are not clinically detected until they are large and often difficult to resect. Technological advances in diagnostic imaging have greatly influenced the surgical planning of these lesions and ultimately the clinical outcome. The intent of this article is to present an imaging algorithm for the effective and efficient workup of liver tumors in pediatric patients. This includes the appropriate timing and use of various imaging modalities, such as conventional radiographs, ultrasound, computed tomography, and magnetic resonance imaging. This article also addresses the use of sedation, intravenous contrast agents, and the benefits and limitations of specific imaging modalities. An overview of the radiologic and pathologic findings in common liver lesions in pediatric patients, as well as individual case examples demonstrating the use of the proposed workup algorithm, is provided. PMID- 25129216 TI - Imaging of nontraumatic acute hip pain in children: multimodality approach with attention to the reduction of medical radiation exposure. AB - Nontraumatic acute hip pain in children is common. However, the presentation and etiology is variable, including difficulty with weight bearing and abnormal gait. Barriers in communication, multiple possible etiologies, and age-specific anatomical variations of the pediatric hip make the evaluation of hip pain in children a difficult clinical diagnosis. Multimodality radiologic approach plays an important role for the evaluation of these children. However, owing to the complexity of pediatric hip disease, children sometimes undergo multiple radiologic examinations, resulting in delay in diagnosis and increased radiation dose. This article focuses on the illustration and discussion of common causes of acute hip pain or limp in children. Current recommendations for the imaging of these patients with specific attention to the ALARA (as low radiation as reasonably achievable) principle of radiation exposure are considered. Examples of the entities discussed are provided. PMID- 25129217 TI - Pediatric interventional radiology and dose-reduction techniques. AB - The pediatric interventional radiology community has worked diligently in recent years through education and the use of technology to incorporate numerous dose reduction strategies. This article seeks to describe different strategies where we can significantly lower the dose to the pediatric patient undergoing a diagnostic or therapeutic image-guided procedure and, subsequently, lower the dose several fold to the staff and ourselves in the process. These strategies start with patient selection, dose awareness and monitoring, shielding, fluoroscopic techniques, and collimation. Advanced features such as cone-beam technology, dose-reduction image processing algorithms, overlay road mapping, and volumetric cross-sectional hybrid imaging are also discussed. PMID- 25129218 TI - Imaging of lumps and bumps in pediatric patients: an algorithm for appropriate imaging and pictorial review. AB - Superficial lumps and bumps are a common presenting complaint in the pediatric patient population. Although encountered frequently, the path to a definitive diagnosis is not always a straightforward one. Imaging offers a valuable tool to aid in this diagnostic challenge. Radiologists must be familiar with pediatric lumps and bumps, their imaging characteristics, and the best way to further evaluate challenging clinical presentations. This will not only allow the radiologist to serve as a valuable asset to the treating physician in choosing the most appropriate imaging modality but also help in accurate diagnosis, all while ensuring the "image gently" principle. An algorithm for imaging in the pediatric patient with lumps and bumps has been presented in this article and a few example entities along with their imaging findings have also been reviewed. PMID- 25129219 TI - Molecular responses in digestive tract of juvenile common carp after chronic exposure to sublethal tributyltin. AB - The effect of long-term exposure to tributyltin (TBT) on the intestine-related biochemical biomarkers in common carp was investigated in this study. Fish were exposed at sub-lethal concentrations of TBT (75 ng/L, 0.75 and 7.5 MUg/L) for 60 days. Multiple biomarkers were measured, including digestive enzymes (trypsin, lipase and amylase), antioxidant responses (malondialdehyde (MDA) and total antioxidative capacity (T-AOC)), RNA/DNA ratio and the expression of digestive related genes (try, lipc and amy). TBT exposure at 0.75 and 7.5 MUg/L led to significantly inhibited activities of all digestive enzymes. At higher concentration of TBT, oxidative stress was apparent as reflected by the significant higher MDA content in the fish intestine, associated with an inhibition of T-AOC activities. After 60 days, the RNA/DNA ratio in fish intestine was significantly lower in groups exposed to TBT at higher concentrations (0.75 and 7.5 MUg/L). In addition, the expression levels of try, lipc and amy in intestine of all treated fish were inhibited, even at the environmental concentration (75 ng/L). Our results suggest that long-term exposure to TBT could result in different responses of intestine-related biochemical biomarkers in fish, which could be used as new potential indicators for monitoring residual TBT present in aquatic environment. PMID- 25129220 TI - A comprehensive insight into bacterial virulence in drinking water using 454 pyrosequencing and Illumina high-throughput sequencing. AB - In order to comprehensively investigate bacterial virulence in drinking water, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential pathogenic bacteria and virulence factors (VFs) in a full-scale drinking water treatment and distribution system. 16S rRNA gene pyrosequencing revealed high bacterial diversity in the drinking water (441-586 operational taxonomic units). Bacterial diversity decreased after chlorine disinfection, but increased after pipeline distribution. alpha-Proteobacteria was the most dominant taxonomic class. Alignment against the established pathogen database showed that several types of putative pathogens were present in the drinking water and Pseudomonas aeruginosa had the highest abundance (over 110/00 of total sequencing reads). Many pathogens disappeared after chlorine disinfection, but P. aeruginosa and Leptospira interrogans were still detected in the tap water. High-throughput sequencing revealed prevalence of various pathogenicity islands and virulence proteins in the drinking water, and translocases, transposons, Clp proteases and flagellar motor switch proteins were the predominant VFs. Both diversity and abundance of the detectable VFs increased after the chlorination, and decreased after the pipeline distribution. This study indicates that joint use of 454 pyrosequencing and Illumina sequencing can comprehensively characterize environmental pathogenesis, and several types of putative pathogens and various VFs are prevalent in drinking water. PMID- 25129221 TI - Brewers' rice induces apoptosis in azoxymethane-induced colon carcinogenesis in rats via suppression of cell proliferation and the Wnt signaling pathway. AB - BACKGROUND: Brewers' rice is locally known as temukut, is a byproduct of the rice milling process, and consists of broken rice, rice bran, and rice germ. Unlike rice bran, the health benefit of brewers' rice has yet to be fully studied. Our present study aimed to identify the chemopreventive potential of brewers' rice with colonic tumor formation and to examine further the mechanistic action of brewers' rice during colon carcinogenesis. METHODS: Male Sprague-Dawley rats were randomly divided into five groups: (G1) normal; (G2) azoxymethane (AOM) alone; and (G3), (G4), and (G5), which were AOM fed with 10%, 20%, and 40% (w/w) of brewers' rice, respectively. Rats in group 2 to 5 were injected intraperitoneally with AOM (15 mg/kg body weight) once weekly for two weeks. Colon tumor incidence and multiplicity was assessed by hematoxylin and eosin (H&E) staining. The expression of beta-catenin, cyclooxygenase-2 (COX-2), and Ki-67 was evaluated by immunohistochemical staining. The apoptosis-inducing activity was analyzed using a TUNEL assay. The data were analyzed using a one-way analysis of variance (ANOVA) with P-value<0.05 was considered significant. RESULTS: Overall analyses revealed that brewers' rice reduced colon tumor incidence and multiplicity. The results from immunohistochemistry analysis also showed that brewers' rice decreased the expression of beta-catenin, COX-2, and Ki-67 in a dose-dependent manner. Furthermore, TUNEL analysis demonstrated that administration of brewers' rice in AOM-induced rat colorectal cancer resulted in a dose-dependent increase in cell apoptosis. CONCLUSIONS: Taken together, our data suggested that brewers' rice can inhibit cell proliferation, induce apoptosis, and suppress COX-2 and beta-catenin expression via the Wnt signaling pathway and holds great promise in the field of chemoprevention as a dietary agent. PMID- 25129222 TI - Quiet standing after carbohydrate ingestion induces sympathoexcitatory and pressor responses in young healthy males. AB - OBJECTIVE: To investigate the role of the sympathetic nervous system in the cardiovascular response to quiet standing in the postprandial state. METHOD: Following a 30min pre-ingestion phase, 14 healthy young male subjects consumed a 600kcal carbohydrate-rich meal. Arterial blood pressure (BP) and heart rate (HR) were recorded for a further 120min. Measurements were obtained (Finometer) in both the supine (5min) and standing (5min) condition every 30min. Power spectral analysis of RR-interval and BP variability was calculated, and heart rate responses to the baroreceptor reflex were calculated to estimate spontaneous baroreflex sensitivity (sBRS). Derived stroke volume (SV) was measured to track changes to postural stress postprandially. RESULTS: Quiet standing increased RR interval low frequency power, ratio of RR-interval low frequency power/high frequency power (ratio of RR LF/HF), and systolic BP low frequency power (SBP LF power), and decreased RR HF power and sBRS before, and after eating. After meal ingestion, SBP LF power increased and sBRS decreased in lying and standing conditions. During quiet standing postprandially, DBP and the mean arterial pressure increased (P<0.01). The increased BP is associated with increased SV (P<0.05) early postprandially, and increased SBP LF power (P<0.01) in the later postprandial phase. SBP LF power is inversely correlated with SV postprandially (P<0.001, R(2)=0.96). CONCLUSION: The findings suggest a sympathetic activation mediated by baroreflex resetting. Quiet standing in the postprandial state enhances sympathetic outflow to the vasculature, increasing BP. SV may be a compensatory factor stabilising BP during quiet standing early postprandially. PMID- 25129223 TI - Hepatitis B prevalence in a multi-ethnic community in South England: a 3 year retrospective study. PMID- 25129224 TI - Safety of street foods in Agartala, North East India. PMID- 25129225 TI - Assessing the relationship between medical residents' perceived barriers to SBIRT implementation and their documentation of SBIRT in clinical practice. PMID- 25129226 TI - Factors affecting preparedness and capacity to manage pandemic influenza: perceptions of healthcare managers. AB - OBJECTIVES: Numerous interventions seeking to increase preparedness for pandemic influenza have been implemented, but low compliance of healthcare providers has been reported in many instances. The aim of this study was to identify factors that affect preparedness for pandemic influenza by examining: hospital managers' perceptions of measures implemented to promote preparedness for pandemic influenza; hospital managers' assessments of the readiness and capability of their hospitals to manage pandemic influenza; and the effectiveness of a national pandemic preparedness programme in Israel over time. STUDY DESIGN: A quasi experiment was conducted following implementation of a national pandemic preparedness programme in Israel. A survey assessed hospital managers' perceptions of the effectiveness of the programme, and the preparedness and capacity of their hospitals to manage pandemic influenza. Two independent evaluations of preparedness for biological threats were conducted, based on a validated tool that included 60 objective parameters. METHODS: Correlations between perceived preparedness and capacity and components of the preparedness programme were analysed using Statistical Package for the Social Sciences Version 17. Stepwise logistic regression was used to determine the components that influence preparedness and capability to manage pandemic influenza. RESULTS: All general hospital managers in Israel were approached twice (first and second evaluations). Ninety-one percent rated themselves as highly/very highly prepared for pandemic influenza, and 87% rated themselves as highly/very highly capable of dealing with pandemic influenza. Strong correlation was found between hospital managers' perceived preparedness and capacity to manage pandemic influenza (rho = 0.761, P = 0.000), and between perceived preparedness and familiarity with the disease (rho = 0.605, P = 0.003). Familiarity with guidelines accounted for 35% of the variance in perceived capability (adjusted R(2) = 0.346, P = 0.002). Inclusion of preparedness evaluations explained an additional 15% of the variance (R(2) change = 0.146, P = 0.026). An increase in mean total score for emergency preparedness was found in the second evaluation compared with the first evaluation. CONCLUSIONS: Familiarity with guidelines and preparedness evaluations affect the perceptions of healthcare managers regarding preparedness and capability to manage pandemic influenza. PMID- 25129227 TI - Socio-economic correlates of functional health literacy among patients of primary health care in Kosovo. AB - OBJECTIVES: Functional health literacy (FHL) has been related to individual characteristics, ill-health and disease knowledge. However, the information about FHL in Kosovo is very limited and thus the aim of this study was to assess the demographic and socio-economic correlates of FHL among users of primary health care in Kosovo, a postconflict country in the Western Balkans. STUDY DESIGN: Cross-sectional study. METHODS: A cross-sectional study was conducted in Kosovo between November 2012-February 2013, including a representative sample of 1035 consecutive primary care users aged >=18 years (60% females; overall mean age: 44.3 +/- 16.9 years; overall response rate: 86%). Test of Functional Health Literacy in Adults (TOFHLA) was used to assess FHL. General linear model and logistic regression were used to assess the association of TOFHLA score with demographic and socio-economic characteristics. RESULTS: Overall, four out of five participants exhibited inadequate or marginal FHL in this Kosovo sample. FHL score was independently and inversely related to age, but positively associated with educational attainment and being in a situation other than unemployed. CONCLUSIONS: Limited or marginal FHL was very common among primary care users in Kosovo and considerably higher than in the neighbouring Serbia. The low health literacy levels in Kosovo may provide an additional barrier towards achievement of health care goals. There is a need to design and implement suitable and effective educational and health system interventions in the Kosovo context. PMID- 25129228 TI - Amplitude-integrated EEG revealed nonconvulsive status epilepticus in children with non-accidental head injury. AB - OBJECTIVE: We describe the clinical course and amplitude-integrated EEG findings in three children with non-accidental head injury and discuss on the importance of continuous aEEG monitoring in infants. METHODS: NCSE was defined as a continuous 30-min seizure or briefer seizures occurring consecutively comprising at least 30 min of any 1-h period. Non-accidental head injury was diagnosed on the basis of neuroimaging findings such as subdural hemorrhage. Antiepileptic treatment was performed with continuous amplitude-integrated EEG monitoring. RESULTS: The age of the patients ranged from 48 days to nine months. All of them had loss of consciousness and seizures on presentation. Nonconvulsive status epilepticus without clinical symptoms were recognized in all patients. Vigorous antiepileptic treatment against nonconvulsive status epilepticus was made in two patients, whereas nonconvulsive status epilepticus disappeared within one hour without additional treatment in one. CONCLUSIONS: Our experience indicates that nonconvulsive status epilepticus were not uncommon in children with non accidental head injury. Continuous amplitude-integrated EEG monitoring will be one of the useful methods in encephalopathic children in order to estimate seizure burden objectively and to treat seizures appropriately. PMID- 25129229 TI - Dietary effect on immunological energetics in mice. AB - Defense against natural aggressors, such as bacterial infections, requires both energy and an immune-cellular response. However, the question as to how these two components are interconnected in small endotherms by means of the host diet remains only poorly understood. Here, we tested in laboratory mice whether dietary proteins and carbohydrates can modulate the interplay between energy expenditure, food intake and the innate and adaptive immune response when confronting a bacterial challenge (Bacillus Calmette-Guerin, BCG). We observed that mice fed with a high protein diet (HP) developed a better immune response associated to increased numbers of circulating monocytes. In addition, HP diet directly influenced the peripheral blood proportions of both T and B lymphocytes even before the BCG challenge. Interestingly, animals that developed this type of immune response after BCG challenge showed an increased rate of metabolism and food consumption before being challenged. Thus, HP diet induced in non-challenged animals a similar energy expenditure and food intake described by BCG-treated mice. These data suggest that a high amount of proteins in diet can modify the energetic and nutrient dynamic in the host causing a better immune reaction against a microbial challenge. PMID- 25129230 TI - Modeling of rhythmic behavior in neutral lipid production due to continuous supply of limited nitrogen: mutual growth and lipid accumulation in microalgae. AB - The relative effects of three precise nitrogen limitation regimes on green micro algae were assessed using the Trebouxiophycean alga Coccomyxa subellipsoidea grown in a chemostatic bioreactor system. The data provides further evidence that growth and triglyceride (TAG) accumulation are concurrent and independently proportional to the degree of nitrogen limitation in algae. Additionally, TAG accumulation was observed to proceed via oscillations with respect to time and percent dry weight quantity. The predator-prey model was applied to fit the experimental data and to obtain the physiological significance of these oscillations. The results determine the conditions of maximum neutral lipid productivity with respect to nitrate stress and highlight an area of potential future research. PMID- 25129231 TI - Effects of solubility properties of solvents and biomass on biomass pretreatment. AB - Hildebrand solubility parameters of biomasses and pretreatment solvents were examined by a method of intrinsic viscosity. This is to be used as basic information in selecting a suitable solvent for biomass pretreatment processes. The effects of mixing1-ethyl-3-methylimidazolium acetate (EMIM-AC) and different solvents, lignin content in a pretreatment solvent, and biomass type on the Hildebrand solubility parameter and thermodynamic properties were carried out and calculated in this work. The Hildebrand solubility parameters of the mixtures are according to those of organic solvents: deltaH[EMIM-AC/DMA]=25.071,000,000Da) at 50% of the cell dry weight (<8h). P3HB also resulted from incubation with acetate, crotonate, or a mixture of hydrolytic depolymerization products. Poly(3-hydroxybutyric acid-co-3 hydroxyvaleric acid) (PHBV) resulted from incubation with valerate or 2 pentenoate. A recycling strategy where abiotic depolymerization of waste PHAs yields feedstock for customized PHA re-synthesis appears feasible, without the need for energy-intensive feedstock purification. PMID- 25129233 TI - The effect of poly-beta-hydroxyalkanoates degradation rate on nitrous oxide production in a denitrifying phosphorus removal system. AB - Poly-beta-hydroxyalkanoates (PHAs) and free nitrous acid (FNA) have been revealed as significant factors causing nitrous oxide (N2O) production in denitrifying phosphorus removal systems. In this study, the effect of PHA degradation rate on N2O production was studied at low FNA levels. N2O production always maintained at approximately 40% of the amount of nitrite reduced independent of the PHA degradation rate. The electrons distributed to nitrite reduction were 1.6 times that to N2O reduction. This indicated that electron competition between these two steps was not affected by the PHA degradation rate. Continuous feed of nitrate was proposed, and demonstrated to reduce N2O accumulation by 75%. While being kept low, a possible compounding effect of a low-level FNA could not be ruled out. The sludge used likely contained both polyphosphate- and glycogen accumulating organisms, and the results could not be simply attributed to either group of organisms. PMID- 25129234 TI - Diversity and dynamics of the microbial community on decomposing wheat straw during mushroom compost production. AB - The development of communities of three important composting players including actinobacteria, fungi and clostridia was explored during the composting of wheat straw for mushroom production. The results revealed the presence of highly diversified actinobacteria and fungal communities during the composting process. The diversity of the fungal community, however, sharply decreased in the mature compost. Furthermore, an apparent succession of both actinobacteria and fungi with intensive changes in the composition of communities was demonstrated during composting. Notably, cellulolytic actinomycetal and fungal genera represented by Thermopolyspora, Microbispora and Humicola were highly enriched in the mature compost. Analysis of the key cellulolytic genes revealed their prevalence at different composting stages including several novel glycoside hydrolase family 48 exocellulase lineages. The community of cellulolytic microbiota also changed substantially over time. The prevalence of the diversified cellulolytic microorganisms holds the great potential of mining novel lignocellulose decomposing enzymes from this specific ecosystem. PMID- 25129236 TI - Absolute and relative quantification of RNA modifications via biosynthetic isotopomers. AB - In the resurging field of RNA modifications, quantification is a bottleneck blocking many exciting avenues. With currently over 150 known nucleoside alterations, detection and quantification methods must encompass multiple modifications for a comprehensive profile. LC-MS/MS approaches offer a perspective for comprehensive parallel quantification of all the various modifications found in total RNA of a given organism. By feeding (13)C-glucose as sole carbon source, we have generated a stable isotope-labeled internal standard (SIL-IS) for bacterial RNA, which facilitates relative comparison of all modifications. While conventional SIL-IS approaches require the chemical synthesis of single modifications in weighable quantities, this SIL-IS consists of a nucleoside mixture covering all detectable RNA modifications of Escherichia coli, yet in small and initially unknown quantities. For absolute in addition to relative quantification, those quantities were determined by a combination of external calibration and sample spiking of the biosynthetic SIL-IS. For each nucleoside, we thus obtained a very robust relative response factor, which permits direct conversion of the MS signal to absolute amounts of substance. The application of the validated SIL-IS allowed highly precise quantification with standard deviations<2% during a 12-week period, and a linear dynamic range that was extended by two orders of magnitude. PMID- 25129237 TI - Generalization from episodic memories across time: a route for semantic knowledge acquisition. AB - The storage of input regularities, at all levels of processing complexity, is a fundamental property of the nervous system. At high levels of complexity, this may involve the extraction of associative regularities between higher order entities such as objects, concepts and environments across events that are separated in space and time. We propose that such a mechanism provides an important route towards the formation of higher order semantic knowledge. The present study assessed whether subjects were able to extract complex regularities from multiple associative memories and whether they could generalize this regularity knowledge to new items. We used a memory task in which subjects were required to learn face-location associations, but in which certain facial features were predictive of locations. We assessed generalization, as well as memory for arbitrary stimulus components, over a 4-h post-encoding consolidation period containing wakefulness or sleep. We also assessed the stability of regularity knowledge across a period of several weeks thereafter. We found that subjects were able to detect the regularity structure and use it in a generalization task. Interestingly, the performance on this task increased across the 4hr post-learning period. However, no differential effects of cerebral sleep and wake states during this interval were observed. Furthermore, it was found that regularity extraction hampered the storage of arbitrary facial features, resulting in an impoverished memory trace. Finally, across a period of several weeks, memory for the regularity structure appeared very robust whereas memory for arbitrary associations showed steep forgetting. The current findings improve our understanding of how regularities across memories impact memory (trans)formation. PMID- 25129235 TI - Fetal exposure to maternal depressive symptoms is associated with cortical thickness in late childhood. AB - BACKGROUND: Maternal depression is one of the most common prenatal complications. The consequences of fetal exposure to maternal depression are poorly understood. The aim of this study is to examine the association between fetal exposure to maternal depressive symptoms and cortical thickness in children 6-9 years old. METHODS: A prospective, longitudinal study of maternal depressive symptoms at 19, 25, and 31 weeks' gestation was followed by acquisition of a structural magnetic resonance imaging scan in 81 children (age, 86.1 +/- 9.9 months). RESULTS: Significant (p < .01) cortical thinning in children primarily in the right frontal lobes was associated with exposure to prenatal maternal depression. The strongest association was at 25 weeks' gestation; exposure to maternal depression at 25 gestational weeks was associated with cortical thinning in 19% of the whole cortex and 24% of the frontal lobes, primarily in the right superior, medial orbital, and frontal pole regions of the prefrontal cortex (p < .01). The significant association between prenatal maternal depression and child externalizing behavior (p < .05) was mediated by cortical thinning in prefrontal areas of the right hemisphere. CONCLUSIONS: The pattern of cortical thinning in children exposed to prenatal maternal depression is similar to patterns in depressed patients and in individuals with risk for depression. Exposure to prenatal depression coupled with subsequent cortical thinning was associated with presence of externalizing behavior in preadolescent children and may be prodromal markers of risk for dysphoria. Vulnerability to prenatal influences at 25 gestational weeks may result from the enormous growth and dramatic structural changes in the nervous system. PMID- 25129238 TI - Hypoxic signature of microRNAs in glioblastoma: insights from small RNA deep sequencing. AB - BACKGROUND: Hypoxia is a critical aspect of the glioma microenvironment and has been associated with poor prognosis and resistance to various therapies. However, the mechanisms responsible for hypoxic survival of glioma cells remain unclear. Recent studies strongly suggest that microRNAs act as critical mediators of the hypoxic response. We thus hypothesized their prominent role in hypoxia resistance in glioblastoma (GBM) and aimed to identify those. RESULTS: With this study, we present the first detailed analysis of small RNA transcriptome of cell line U87MG, a grade IV glioma cell line, and its alteration under hypoxic condition. Based on deep sequencing and microarray data, we identify a set of hypoxia regulated microRNAs, with the miR-210-3p and its isomiRs showing highest induction in GBM cell lines U87MG and U251MG. We show miR-210-3p, miR-1275, miR 376c-3p, miR-23b-3p, miR-193a-3p and miR-145-5p to be up-regulated, while miR-92b 3p, miR-20a-5p, miR-10b-5p, miR-181a-2-3p and miR-185-5p are down-regulated by hypoxia. Interestingly, certain hypoxia-induced miRNAs are also known to be over expressed in GBM tumors, suggesting that hypoxia may be one of the factors involved in establishing the miRNA signature of GBM. Transcription factor binding sites for Hypoxia inducible factor 1 A (HIF1A) were identified in the promoter region (5 kb upstream) of 30 hypoxia-induced miRNAs. HIF-1A over-expression and silencing studies show regulation of specific miRNAs, including miR-210-3p, to be HIF1A dependent. On the other hand, miR-210-3p leads to an increase in transcriptional activity of HIF and its target genes vascular endothelial growth factor (VEGF) and carbonic anhydrase 9 (CA9). MiR-210-3p levels were found to be high in GBM patient samples and showed good correlation with the known hypoxia markers CA9 and VEGF. We show that miR-210-3p promotes hypoxic survival and chemoresistance in GBM cells and targets a negative regulator of hypoxic response, HIF3A. Additionally, a total of 139 novel miRNAs were discovered by the analysis of deep sequencing data and three of these were found to be differentially expressed under hypoxia. CONCLUSIONS: Overall, our study reveals a novel miRNA signature of hypoxia in GBM and suggests miR-210-3p to be an oncogenic player and a novel potential intrinsic marker of hypoxia in glioblastoma. PMID- 25129239 TI - Quantitative electroencephalogram utility in predicting conversion of mild cognitive impairment to dementia with Lewy bodies. AB - Mild cognitive impairment (MCI) as a precursor of dementia with Lewy bodies (DLB) is the focus of recent research, trying to explore the early mechanisms and possible biomarkers of DLB. Quantitative electroencephalogram (QEEG) methods are able to differentiate early DLB from Alzheimer's disease (AD). The aim of the present study was to assess whether QEEG abnormalities, characterized by dominant frequency <8 Hz and dominant frequency variability >1.5 Hz, typical of early DLB, are already present at the stage of MCI and to evaluate whether EEG abnormalities can predict the development of DLB. Forty-seven MCI subjects were followed for 3 years. EEG recordings were obtained at admission and at the end of the study. At the end of follow-up, 20 subjects had developed probable DLB (MCI-DLB), 14 had probable AD (MCI-AD), 8 did not convert to dementia, 5 developed a non-AD/DLB dementia. One hundred percent of MCI-DLB showed EEG abnormalities at admission. Ninety three percent of MCI-AD maintained a normal EEG throughout the study. QEEG may represent a powerful tool to predict the progression from MCI to DLB with a sensitivity and specificity close to 100%. PMID- 25129240 TI - SNCA variants rs2736990 and rs356220 as risk factors for Parkinson's disease but not for amyotrophic lateral sclerosis and multiple system atrophy in a Chinese population. AB - Previous studies found that polymorphisms rs2736990 and rs356220 in the alpha synuclein (SNCA) gene increase the risk for Parkinson's disease (PD) in a Caucasian population. In consideration of the overlapping of clinical manifestations and pathologic characteristics among PD, amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA), the possible associations of these 2 polymorphisms and 3 neurodegenerative diseases were studied in the Chinese population. A total of 1011 PD, 778 sporadic ALS (SALS), 264 MSA patients, and 721 healthy controls (HCs) were studied. All subjects were genotyped for the 2 polymorphisms using polymerase chain reaction and direct sequencing. Significant differences in the genotype frequencies (p = 0.0188 and 0.0064, respectively) and minor allele frequencies (MAFs) (p = 0.0065 and 0.0095, respectively) of rs2736990 and rs356220 were observed between the PD patients and HCs. Moreover, significant differences were found between the early-onset PD patients (<50 years) and matched controls but not in the late-onset PD patients (>=50 years). However, no differences were observed between subgroups with regard to clinical features, such as sex, onset symptoms (tremor or rigidity), cognition (normal or abnormal), and anxiety and depression (presence or absence). No significant differences were found in the genotype frequencies and MAFs of these 2 single-nucleotide polymorphisms between SALS patients and HCs and between MSA patients and HCs. No significant differences were found between subgroups with regard to the clinical presentation of SALS and MSA. Our results show that rs2736990 and rs356220 in SNCA decreased the risk for PD in a Chinese population. These candidate polymorphisms were unlikely to be the causes of SALS and MSA in this population. PMID- 25129241 TI - Predictable dental rehabilitation in maxillomandibular reconstruction with free flaps. The role of implant guided surgery. AB - The reconstruction of maxillomandibular defects secondary to oral cancer surgery, represent a great challenge for Maxillofacial surgeons. During the last decades the reconstructive surgery has experimented a big advance due to the development of the microsurgical techniques. At present, we are able to reconstruct complex defects using free flaps that provide both soft and bone tissue. Fibula, iliac crest and scapula free flaps have been the three classic options for the maxillomandibular reconstruction owing to the amount of bone that this flaps provide, allowing the posterior dental rehabilitation with implants. Today, our objective it is not only the aesthetic reconstruction, but also the functional reconstruction of the patients enhancing their life quality. Guided implant surgery in free flap reconstructed patients has become an essential tool, helping to define the exact position of the dental implant in the flap. In this way it is possible to look for the areas with better bone conditions, avoiding the osteosynthesis material used to fixate the flap with the native bone and deciding the best biomechanical option, in terms of number and situation of the implants, for the future dental prostheses. In summary, using the guided implant surgery, it is possible to design an exact and predictable dental implant rehabilitation in patients with oral cancer who are reconstructed with free microvascular flap, resulting in an optimal aesthetic and functional result. PMID- 25129242 TI - Morphological and topographical characteristics of posterior supernumerary molar teeth: an epidemiological study on 25,186 subjects. AB - OBJECTIVES: To investigate the prevalence , gender difference , arch , morphology and position within the arch of supernumerary molar (SM) teeth in a referred Italian Caucasian population. STUDY DESIGN: Records of 25,186 young patients were evaluated. Only data related to supernumerary teeth in the posterior region of the jaws were analyzed. The diagnosis of hyperdontia was formulated during the clinical and radiological examinations based on panoramic radiographs. Statistical analysis was conducted at level of subjects in the assessment of prevalence of SMs and sex ratio. Statistical analysis was conducted at level of teeth according to their morphological and topographic characteristics. The analysis of association between supernumerary morphology and arch, between supernumerary position and arch and between morphology and position was performed using the chi2 test (P<= 0.05). RESULTS: 61 posterior supernumerary teeth were found in 45 patients. The male to female ratio was 2.5:1 ;the mean age was 21.23 (IC:95%).The SMs were found more frequently in the maxilla (62.3%) than in the mandible; supernumerary teeth (60.7%) were more frequent than supplemental teeth. The SMs were mostly of tuberculate shape (56.8%) and paramolars teeth (64.9%) were more common than distomolars. 54% of teeth were erupted in the arch. No statistically significant relationship were found between the supernumerary teeth shape and the arch (P= 0.087) , between supernumerary teeth position and the arch (P=0.511) and between morphology and position (P=0.216). CONCLUSIONS: Epidemiological studies related to supernumerary teeth can be useful to clinicians in the early diagnosis of this anomaly. In this retrospective study the prevalence of SMs was 0.18%. SMs were more frequent in males and in the maxilla. Supernumerary were more frequent than supplemental; the conical morphology and paramolar position were the most common shape and position. PMID- 25129243 TI - Significant association of MTHFD1 1958G>A single nucleotide polymorphism with nonsyndromic cleft lip and palate in Indian population. AB - OBJECTIVE: Nonsyndromic cleft lip and palate (NSCLP) is genetically distinct from those with syndromic clefts, and accounts for ~70% of cases with Oral clefts. Folate, or vitamin B9, is an essential nutrient in our diet. Allelic variants in genes involved in the folate pathway might be expected to have an impact on risk of oral clefts. Given the key role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) in folate metabolism, it would be of significant interest to assess its role in NSCLP etiology. STUDY DESIGN: The present study aims at examining the association between MTHFD1 1958G>A polymorphism and NSCLP risk by conducting a case-control study in south Indian population. Our sample comprised of 142 cases with nonsyndromic clefts and 141 controls without clefts or family history of clefting. The MTHFD1 1958G>A polymorphism was genotyped using PCR-RFLP. RESULTS: An increased risk was found for the heterozygous 1958GA (OR=2.44; P=0.020) and homozygous 1958AA (OR=2.45; P=0.012) genotypes in the children. When the dominant model (AG+AA vs GG) was applied the risk remained the same as co-dominant model, but the level of significance increased (OR=2.44; P=0.002). CONCLUSION: The results indicated the MTHFD1 1958G>A polymorphism to be one of the important genetic determinants of NSCLP risk in South Indian subjects. PMID- 25129244 TI - Ameloblastomas: clinicopathological features from 70 cases diagnosed in a single oral pathology service in an 8-year period. AB - Ameloblastomas are odontogenic tumors that can present some distinct clinicopathological profiles when comparing different populations and studies. OBJECTIVES: The aim of the present study was to analyze the clinicopathological features from a series of ameloblastomas diagnosed in a single Oral Pathology service in Brazil in an 8-year period. STUDY DESIGN: The files were revised and all cases diagnosed as ameloblastomas in the period were retrieved. All hematoxylin and eosin stained histological slides were reviewed and all clinical and radiological information were obtained through a review of the laboratory forms. Data were descriptively analyzed and a comparison was performed with the different ameloblastomas subtypes. RESULTS: Seventy ameloblastomas composed the final sample, including 57 (81%) solid/multicystic, 9 (13%) unicystic, 2 (3%) desmoplastic and 2 (3%) peripheral ameloblastomas. Mean age of the affected patients was in the forth decade of life and there was a slight male predominance. Most tumors presented as multilocular radiolucencies, were located in the posterior mandible and showed the follicular and plexiform histological patterns. There was no difference on the mean age of the patients affected by solid and unicystic ameloblastomas. CONCLUSIONS: The present results showed that the clinicopathological features of the ameloblastomas included in this Brazilian sample were similar to the features described in most other worldwide populations. PMID- 25129245 TI - Analysis of methylation and mRNA expression status of FADD and FAS genes in patients with oral squamous cell carcinoma. AB - BACKGROUND: Apoptosis is an important mechanism that is responsible for the physiological deletion of harmful, damaged, or unwanted cells. Changed expression of apoptosis-related genes may lead to abnormal cell proliferation and finally to tumor genesis. Our aims were to analyze the promoter methylation and gene expression profiles of FADD and FAS genes in risk of OSCC. MATERIAL AND METHODS: we analyze the promoter methylation status of FADD and FAS genes using Methylation - Specific PCR (MSP) in 86 OSCC tissues were kept in paraffin and 68 normal oral tissues applied as control. Also, FADD and FAS genes expression were analyzed in 19 cases and 20 normal specimens by Real-Time Reverse-Transcripts PCR. RESULTS: Aberrant promoter methylation of FADD and FAS genes were detected in 12.79 % (11 of 86) and 60.46 % (52 of 86) of the OSCC cases, respectively, with a significant difference between cases and healthy controls for both FADD and FAS genes (P < 0.001). The gene expression analysis showed statistically significant difference between cases and healthy controls for both FADD (p<0.02) and FAS (p<0.007) genes. CONCLUSIONS: To the best our knowledge, the data of this study are the first report regarding, the effect of promoter hypermethylation of the FADD and FAS genes in development of OSCC. To confirm the data, it is recommended doing further study in large sample sizes in various genetic populations. PMID- 25129246 TI - Association of -1082 interleukin-10 gene polymorphism in Peruvian adults with chronic periodontitis. AB - OBJECTIVES: The aim of this study was to assess association of the -1082 IL-10 gene polymorphism with chronic periodontitis CP in a Peruvian population. STUDY DESIGN: Samples of venous blood and DNA were obtained from 106 Peruvian subjects: a) 53 periodontally healthy; and b) 53 with CP. The association of the -1082 IL 10 promoter sequences was assessed by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Student's t test were used to assess the clinical parameters, as well as the chi2 test and the odds ratio (OR), with 95% confidence intervals (CI) used performed for estimates regarding genotype and allele frequencies. RESULTS: There were statistically significant differences between groups regarding the mean bleeding on probing, mean attachment level and mean probing depth (p < 0.00001) indicating that the matching based on the evaluated groups was adequate. The chi2 test found a statistically significant imbalance of genotypes between groups (p = 0.0172). The prevalence of CP was significantly higher in subjects harboring at least one A allele at position 1082 (AA and GA genotypes) in comparison to patients with the GG genotype (OR = 2.96; CI: 0.52; 5.41; p = 0.0099). Equally, subjects with the AA genotype were significantly associated to a diagnosis of CP (OR = 2.71; CI: 0.38; 5.04; p = 0.0231). On the other hand, subjects presenting a healthy periodontal status presented at least one G allele in comparison with the AA genotype (OR = 0.37; CI: 0.05, 0.69; p = 0.0231). For subjects with the GG genotype, the same positive association was observed (OR = 0.34; CI: 0.06, 0.62; p = 0.0099). There were no significant differences between groups amongst subjects with the GA genotype (OR = 1.19; CI: 0.22, 2.16; p = 0.6774). CONCLUSIONS: Within the limits of this study, IL-10 gene polymorphism at position -1082 does not appear to be associated to CP. Conversely, subjects with AA genotype seem to be at an increased risk of developing CP. PMID- 25129247 TI - Effect of low-dose dexketoprofen trometamol and paracetamol on postoperative complications after impacted third molar surgery on healthy volunteers: A pilot study. AB - OBJECTIVES: The aim of the present study was to investigate the analgesic and anti-inflammatory effects of dexketoprofen trometamol (DT) and paracetamol on deep acute somatic pain and inflammation in patients undergoing impacted third molar surgery. This study was planned to present benefits that we could obtain with low burden of drug. STUDY DESIGN: Effects of drugs, which were administered preemptively before the procedure, on pain, mouth-opening limitation, and swelling were assessed by visual analogue scale (VAS), magnetic resonance imaging (MRI), and mouth-opening measurement. Following surgery, time intervals when the patients first need to receive the drug were measured. RESULTS: The VAS scores of the patients were lower in the side treated with DT than that in the paracetamol treated side. There was no significant difference between the groups in terms of mouth-opening limitation. MRI recordings revealed that swelling was lower in the side treated with paracetamol than DT treated side. CONCLUSIONS: Administration of the drugs before surgery contributed to the postoperative patient comfort. The analgesic activity of 12.5 mg dose of DT was similar to, even better than, the analgesic activity of 500 mg dose of paracetamol; however, DT had insufficient anti-inflammatory efficacy. PMID- 25129248 TI - The clinical significance of CDK1 expression in oral squamous cell carcinoma. AB - OBJECTIVES: To evaluate the clinical significance of cyclin-dependent kinase 1 (CDK1) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical methods. STUDY DESIGN: Immunohistochemical expression of CDK1 was compared with various clinicopathological features in 77 OSCC and 60 controlled epithelia adjacent to the tumours. In addition, correlation of CDK1 expression and prognostic and the 5-year accumulative survival rate of OSCC were investigated. RESULTS: The CDK1 protein was expressed in 52 cases of 77 tumor tissues (67.5%), compared with 21 cases of 60 controlled (35.0%). The expression of CDK1 was significantly correlated with the histological grade of OSCC (P<0.05). The CDK1 protein was over-expressed in recurrent tumors or in those with lymph node metastasis. Statistical analysis showed a significant reduction in the 5-year accumulative survival rate in CDK1 positive cases compared with CDK1 negative cases (P<0.05). Namely, the CDK1 positive patients had poor prognosis. CONCLUSIONS: The expression of CDK1 might serve as malignant degree and prognostic markers for the survival of OSCC. PMID- 25129249 TI - Odontogenic myxofibroma: a concise review of the literature with emphasis on the surgical approach. AB - PURPOSE: The aim of this work is to report a review of the literature concerning epidemiology, clinical and radiographic features as well as treatment of odontogenic myxofibroma (MF). METHODS: The PubMed database was searched using the following keywords: "odontogenic myxofibroma", "odontogenic fibromyxoma", "myxofibroma of the jaw" and "fibromyxoma of the jaw". RESULTS: Fifteen articles reporting the experience with 24 patients were identified. Male/female ratio was 1:1.4 and the average age 29.5 years. The most frequent location was the mandible. In 66.7% of the cases the radiographic appearance was a multilocular radiolucency. Swelling was observed in 13 patients (92.86%), varying degrees of pain in 5 (35.71%) and paresthesia in only one patient (7.14%). Six out of 24 patients (26.09%) were treated with radical surgery and 17 out of 24 (73.91%) with a conservative approach. In two out of 21 cases (9.52%) a recurrence was reported. CONCLUSIONS: MF is an extremely rare tumour and no agreement exist on the causes of its development. According to the present review, the choice of treatment should depend on variables such as localization, presence of a primary or of a recurrent lesion, age, general medical conditions and aesthetic needs of the patient. PMID- 25129250 TI - Transition from glass to digital slide microscopy in the teaching of oral pathology in a Brazilian dental school. AB - OBJECTIVES: Several medical and dental schools have described their experience in the transition from conventional to digital microscopy in the teaching of general pathology and histology disciplines; however, this transitional process has scarcely been reported in the teaching of oral pathology. Therefore, the objective of the current study is to report the transition from conventional glass slide to virtual microscopy in oral pathology teaching, a unique experience in Latin America. STUDY DESIGN: An Aperio ScanScope(r) scanner was used to digitalize histological slides used in practical lectures of oral pathology. The challenges and benefits observed by the group of Professors from the Piracicaba Dental School (Brazil) are described and a questionnaire to evaluate the students' compliance to this new methodology was applied. RESULTS: An improvement in the classes was described by the Professors who mainly dealt with questions related to pathological changes instead of technical problems; also, a higher interaction with the students was described. The simplicity of the software used and the high quality of the virtual slides, requiring a smaller time to identify microscopic structures, were considered important for a better teaching process. CONCLUSIONS: Virtual microscopy used to teach oral pathology represents a useful educational methodology, with an excellent compliance of the dental students. PMID- 25129251 TI - Influence of bone parameters on peri-implant bone strain distribution in the posterior mandible. AB - OBJECTIVES: The success rate of dental implants depends on the type of bone at the implant site. The purpose of the present study was to investigate the effects of the bone parameters at the implant-placement site on peri-implant bone strain distributions. STUDY DESIGN: The morphologies and bone densities of seventy-five potential implant sites in the posterior mandible were measured using computed tomography (CT). Based on the CT data, we defined bone parameters (low and high in terms of cancellous-bone density and crestal-cortical bone density, and thin and thick in terms of crestal-cortical bone thickness), and we constructed finite element models simulating the various bone types. A buccolingual oblique load of 200 N was applied to the top of the abutment. The von Mises equivalent (EQV) strains in the crestal-cortical bone and in the cancellous bone around the implant were calculated. RESULTS: Cancellous-bone density greatly affected the maximum EQV strain regardless of the density and thickness of the crestal cortical-bone. The maximum EQV strains in the crestal cortical-bone and the cancellous bone in the low-density cancellous-bone models (of 150 Hounsfield units (HU)) were 1.56 to 2.62-fold and 3.49 to 5.31-fold higher than those in the high-density cancellous-bone models (of 850 HU), respectively. The crestal cortical-bone density affected the maximum EQV strains in the crestal cortical bone and in the cancellous bone in the low-density cancellous-bone models. The crestal cortical-bone thickness affected the maximum EQV strains in the cancellous bone and in the crestal cortical-bone in the low-density cancellous bone models. CONCLUSIONS: Our results confirm the importance of bone types for the peri-implant bone strain distribution. Cancellous-bone density may be a critical factor for peri-implant bone strain. PMID- 25129252 TI - In vitro preliminary study of osteoblast response to surface roughness of titanium discs and topical application of melatonin. AB - OBJECTIVES: To observe human osteoblast behavior cultured in vitro on titanium discs (Ti) in relation to surface roughness and melatonin application. STUDY DESIGN: Human osteoblasts (MG-63) were cultured on 60 Ti6Al4V discs divided into three groups: Group I: discs treated with dual acid etching; Group II dual acid etching and blasting with calcium phosphate particles; Group III (control) machined discs. Surface roughness and topography of the discs were examined with scanning electron microscope (SEM) and confocal laser scanning electron microscope( CLSM). Osteoblast adhesion, proliferation and cell morphology were determined by means of fluorescence microscopy with Image-Pro Plus software and SEM. RESULTS: Group II presented the roughest discs, while the least rough were Group III. Cell adhesion was greatest in Group II. The addition of melatonin improved cell proliferation. CONCLUSIONS: 1. Surface treatments (dual acid etching, calcium phosphate impaction) increase surface roughness in comparison with machined titanium. 2. Greater surface roughness tends to favor cell adhesion after 24-hour cell culture. 3. The addition of melatonin tends to favor osteoblast proliferation. PMID- 25129253 TI - Mechanical behavior of provisional implant prosthetic abutments. AB - INTRODUCTION: Implant-supported prostheses have to overcome a major difficulty presented by the morphology and esthetics of peri-implant tissues in the anterior sector. Diverse therapeutic techniques are used for managing the mucosa adjacent to the implant and the most noteworthy is immediate/deferred fixed provisionalization. OBJECTIVES: In vitro testing of strength and deformation of implant prosthetic abutments made from different materials (Titanium/PEEK/methacrylate). MATERIAL AND METHODS: Forty Sweden & Martina(r) implant prosthetic abutments (n=40) were divided into five groups: Group MP: methacrylate provisional abutments with machined titanium base; Group PP: Polyether ether ketone (PEEK) provisional abutments; Group TP: titanium provisional abutments; Group TAD: titanium anti-rotational definitive abutments; Group TRD: titanium rotational definitive abutments. Their mechanical behavior under static loading was analyzed. Samples were examined under a microscope to determine the type of fracture produced. RESULTS AND CONCLUSIONS: Definitive anti rotational titanium abutments and definitive rotational titanium abutments achieved the best mean compression strength, while PEEK resin provisional abutments obtained the lowest. The group that showed the greatest elastic deformation was the group of titanium provisional abutments. PMID- 25129254 TI - Pfeiffer syndrome: clinical and genetic findings in five Brazilian families. AB - Pfeiffer syndrome (PS) is mainly characterized by craniosysnostosis, midface hypoplasia, great toes with partial syndactyly of the digits, broad and medially deviated thumbs. It is caused by allelic mutations in the fibroblast growth factor receptor 1 and 2 (FGFR1 and 2) genes. This study describes the clinical and genetic features of five Brazilian families affected by PS. All patients exhibited the classical phenotypes related to PS. The genetic analysis was able to detect the mutations Cys278Phe, Cys342Arg, and Val359Leu in three of these families. Two mutations were de novo, with one familial. We identified pathogenic mutations in four PS cases in five Brazilian families by PCR sequencing of FGFR1 exon 5 and FGFR2 exons 5, 8, 10, 11, 15, and 16. The clinical and genetic aspects of these families confirm that this syndrome can be clinically variable, with different mutations in the FGFR2 responsible for PS. PMID- 25129255 TI - Genetic control of nerve conduction velocity may influence multiple sclerosis phenotype. AB - This commentary highlights the article by Lemcke et al that reports a polymorphism in the Inpp4b gene, which is associated with increased risk of developing multiple sclerosis. PMID- 25129256 TI - Nerve conduction velocity is regulated by the inositol polyphosphate-4 phosphatase II gene. AB - Impairment of nerve conduction is common in neurodegenerative and neuroinflammatory diseases such as multiple sclerosis (MS), and measurement of evoked potentials (visual, motor, or sensory) has been widely used for diagnosis and recently also as a prognostic marker for MS. We used a classical genetic approach to identify novel genes controlling nerve conduction. First, we used quantitative trait mapping in F2 progeny of B10/SJL mice to identify EAE31, a locus controlling latency of motor evoked potentials (MEPs) and clinical onset of experimental autoimmune encephalomyelitis. Then, by combining congenic mapping, in silico haplotype analyses, and comparative genomics we identified inositol polyphosphate-4-phosphatase, type II (Inpp4b) as the quantitative trait gene for EAE31. Sequence variants of Inpp4b (C/A, exon 13; A/C, exon 14) were identified as differing among multiple mouse strains and correlated with individual cortical MEP latency differences. To evaluate the functional relevance of the amino acid exchanges at positions S474R and H548P, we generated transgenic mice carrying the longer-latency allele (Inpp4b(474R/548P)) in the C57BL/6J background. Inpp4b(474R/548P) mice exhibited significantly longer cortical MEP latencies (4.5 +/- 0.22 ms versus 3.7 +/- 0.13 ms; P = 1.04 * 10(-9)), indicating that INPP4B regulates nerve conduction velocity. An association of an INPP4B polymorphism (rs13102150) with MS was observed in German and Spanish MS cohorts (3676 controls and 911 cases) (P = 8.8 * 10(-3)). PMID- 25129257 TI - A novel frameshift mutation in BLM gene associated with high sister chromatid exchanges (SCE) in heterozygous family members. AB - The Bloom syndrome (BS) is an autosomic recessive disorder comprising a wide range of abnormalities, including stunted growth, immunodeficiency, sun sensitivity and increased frequency of various types of cancer. Bloom syndrome cells display a high level of genetic instability, including a 10-fold increase in the sister chromatid exchanges (SCE) level. Bloom syndrome arises through mutations in both alleles of the BLM gene, which was identified as a member of the RecQ helicase family. In this study, we screened a Tunisian family with three BS patients. Cytogenetic analysis showed several chromosomal aberrations, and an approximately 14-fold elevated SCE frequency in BS cells. A significant increase in SCE frequency was observed in some family members but not reaching the BS patients values, leading to suggest that this could be due to the heterozygous profile. Microsatellite genotyping using four fluorescent dye-labeled microsatellite markers revealed evidence of linkage to BLM locus and the healthy members, sharing higher SCE frequency, showed heterozygous haplotypes as expected. Additionally, the direct BLM gene sequencing identified a novel homozygous frameshift mutation c.3617-3619delAA (p.K1207fsX9) in BS patients and a heterozygous BLM mutation in the family members with higher SCE frequency. Our findings suggest that this latter mutation likely leads to a reduced BLM activity explaining the homologous recombination repair defect and, therefore, the increase in SCE. Based on the present data, the screening of this mutation could contribute to the rapid diagnosis of BS. The genetic confirmation of the mutation in BLM gene provides crucial information for genetic counseling and prenatal diagnosis. PMID- 25129259 TI - Invasive fungal disease in systemic lupus erythematosus: a systematic review of disease characteristics, risk factors, and prognosis. AB - OBJECTIVES: Invasive fungal disease (IFD) is a life-threatening complication of systemic lupus erythematosus (SLE) and/or its treatment. We conducted a systematic review to characterize IFD in SLE and identify risk factors and outcomes. METHODS: MEDLINE, Embase, and Web of Science were searched up to June 2013 using MeSH terms and keywords pertaining to SLE and IFD. Two independent reviewers selected adult cohort studies and case series/reports on IFD in SLE based on the established classification criteria for both diseases. RESULTS: In total, 393 cases from 182 studies met the criteria for inclusion. Cryptococcus spp., Aspergillus spp., and Candida spp. were the most common fungal pathogens. Cohorts described IFD in 0.6-3.2% of SLE inpatients and 0.28% of SLE outpatients. IFD occurred at a median of 2 years of disease duration (IQR: 0.5-7.1), and 39% of cases occurred within the first year of SLE. Disease activity and corticosteroid dose >60mg/day emerged as risk factors for IFD. IFD was associated with a mortality rate of 53% (161/316 cases), and worse in the absence of antifungal therapy (n = 43). Overall, 44 cases of IFD were only diagnosed on autopsy. CONCLUSIONS: Our systematic review confirms the severe sequelae of IFD in SLE. Cases occurred in patients with active SLE, who were on high daily corticosteroids doses and at early stages of disease. This highlights the role of poor disease control and a high "net state of immunosuppression" in risk. IFD in SLE should be prospectively examined in the modern era. PMID- 25129260 TI - Osseous sarcoidosis: clinical characteristics, treatment, and outcomes- experience from a large, academic hospital. AB - OBJECTIVE: Osseous sarcoidosis has been infrequently reported. We aimed to characterize the distribution of lesions, clinical presentation, treatment, and outcomes for osseous sarcoidosis. METHODS: Cases of osseous sarcoidosis were identified by directed inquiry to clinicians and electronic query. Cases were defined as having pathologic evidence of non-caseating granulomas on bone biopsy or evidence of osseous lesions on imaging attributable to sarcoidosis in patients with known sarcoidosis. Detailed characteristics were obtained by medical record review. RESULTS: We identified a total of 20 cases of osseous sarcoidosis. Osseous lesions were detected by imaging during the initial sarcoidosis presentation in 60% of cases. In those who had a prior diagnosis of sarcoidosis, the median duration of sarcoidosis before detection of osseous involvement was 4.3 years. Symptoms were present in 50% of cases. All cases had more than one bone involved. The axial skeleton was involved in the majority of cases (90%), primarily the pelvis and the lumbar spine. Most cases required no treatment (55%); a minority of cases (45%) were treated, most often with prednisone, methotrexate, or hydroxychloroquine. Two cases required multiple immunosuppressants, including tumor necrosis factor inhibitors, for refractory symptomatic osseous sarcoidosis. Treated cases were younger than those who were untreated. At last follow-up, most cases (85%) were asymptomatic from osseous lesions. CONCLUSIONS: In this case series of osseous sarcoidosis from a single center, most patients had multiple bones affected and had other systemic manifestations of sarcoidosis. A minority required treatment for relief of symptoms, and most cases were asymptomatic at last follow-up. PMID- 25129258 TI - Genetics of psychotropic medication induced side effects in two independent samples of bipolar patients. AB - The treatment of bipolar disorder (BD) usually requires combination therapies, with the critical issue of the emergence of adverse drug reactions (ADRs) and the possibility of low treatment adherence. Genetic polymorphisms are hypothesized to modulate the pharmacodynamics of psychotropic drugs, representing potential biological markers of ADRs. This study investigated genes involved in the regulation of neuroplasticity (BDNF, ST8SIA2), second messenger cascades (GSK3B, MAPK1, and CREB1), circadian rhythms (RORA), transcription (SP4, ZNF804A), and monoaminergic system (HTR2A and COMT) in the risk of neurological, psychic, autonomic, and other ADRs. Two independent samples of BD patients naturalistically treated were included (COPE-BD n = 147; STEP-BD n = 659). In the COPE-BD 34 SNPs were genotyped, while in the STEP-BD polymorphisms in the selected genes were extracted from the genome-wide dataset. Each ADRs group was categorized as absent-mild or moderate-severe and logistic regression with appropriate covariates was applied to identify possible risk genotypes/alleles. 58.5 and 93.5 % of patients were treated with mood stabilizers, 44.2 and 50.7 % were treated with antipsychotics, and 69.4 and 46.1 % were treated with antidepressants in the COPE-BD and STEP-BD, respectively. Our findings suggested that ST8SIA2 may be associated with psychic ADRs, as shown in the COPE-BD (rs4777989 p = 0.0017) and STEP-BD (rs56027313, rs13379489 and rs10852173). A cluster of RORA SNPs around rs2083074 showed an effect on psychic ADRs in the STEP-BD. Trends supporting the association between HTR2A and autonomic ADRs were found in both samples. Confirmations are needed particularly for ST8SIA2 and RORA since the few available data regarding their role in relation to psychotropic ADRs. PMID- 25129261 TI - Is there a polysomnographic signature of augmentation in restless legs syndrome? AB - OBJECTIVE: Augmentation of restless legs syndrome (RLS) is a potentially severe side-effect of dopaminergic treatment. Data on objective motor characteristics in augmentation are scarce. The aim of this study was to investigate in detail different variables of leg movements (LM) in untreated, treated, and augmented RLS patients. METHODS: Forty-five patients with idiopathic RLS [15 untreated, 15 treated (non-augmented), 15 augmented] underwent RLS severity assessment, one night of video-polysomnography with extended electromyographic montage, and a suggested immobilization test (SIT). RESULTS: Standard LM parameters as well as periodicity index (PI) and muscle recruitment pattern did not differ between the three groups. The ultradian distribution of periodic leg movements (PLM) in sleep during the night revealed significant differences only during the second hour of sleep (P <0.05). However, augmented patients scored highest on RLS severity scales (P <0.05) and were the only group with a substantial number of PLM during the SIT. CONCLUSION: This study demonstrates that polysomnography is of limited usefulness for the diagnosis and evaluation of RLS augmentation. In contrast, the SIT showed borderline differences in PLM, and differences on subjective scales were marked. According to these results, augmentation of RLS is a phenomenon that predominantly manifests in wakefulness. PMID- 25129262 TI - Restless legs syndrome and central nervous system gamma-aminobutyric acid: preliminary associations with periodic limb movements in sleep and restless leg syndrome symptom severity. AB - BACKGROUND: Previous research has demonstrated abnormalities in glutamate and N acetyl aspartate (NAA) in the thalamus in individuals with restless legs syndrome (RLS) compared with healthy matched controls. However, levels of these transmitters in other RLS-related brain areas and levels of the most common inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have not been assessed. METHODS: This study examined GABA, glutamate, and NAA levels in the dorsal anterior cingulate cortex (ACC), thalamus and cerebellum with the use of proton magnetic resonance spectroscopy ((1)H-MRS) at 4 tesla (4 T) and Megapress difference-editing in 18 subjects with RLS and a matched control group without RLS. Actigraphy was performed on the nights before scans to assess periodic limb movements of sleep (PLMS). RESULTS: Levels of GABA, glutamate, and NAA were no different between RLS and control subjects in any of the three voxels of interest. However, GABA levels were positively correlated with both PLM indices and RLS severity in the thalamus and negatively with both of these measures in the cerebellum in RLS subjects. In addition, NAA levels were higher in the ACC in RLS than in controls. CONCLUSION: Our preliminary data suggest that known cerebellar-thalamic interactions may modulate the intensity of RLS sensory and motor symptoms. In addition, anterior cingulate cortex may be associated with the affective components of the painful symptoms in this disorder. PMID- 25129263 TI - Coronary angioscopy and optical coherence tomography for confirmation of drug coated neointimal plaque after paclitaxel-coated balloon angioplasty for in-stent restenosis. PMID- 25129264 TI - BDNF expression of macrophages and angiogenesis after myocardial infarction. PMID- 25129265 TI - Coronary artery aneurysm formation within everolimus-eluting bioresorbable stent. PMID- 25129267 TI - Cost-effectiveness analysis of Chagas' cardiomyopathy: early diagnosis and prevention should be the target for comparison. PMID- 25129266 TI - Meta-analysis of circulating 25-hydroxyvitamin D levels and risk of cardiovascular and all-cause mortality in elderly population. PMID- 25129268 TI - The effects of thiamine treatment on pre-diabetic versus overt diabetic rat hearts: role of non-oxidative glucose pathways. PMID- 25129269 TI - Intrinsic bleeding risk in patients with uninterrupted oral anticoagulation undergoing cardiac implantable electronic device procedures: a pilot study. PMID- 25129270 TI - Delay to diagnosis amongst patients with catecholaminergic polymorphic ventricular tachycardia. PMID- 25129271 TI - Determinants and implications of elevated soluble ST2 levels in heart failure. PMID- 25129272 TI - Association of age and gender with anterior location of STEMI. PMID- 25129273 TI - Is IL-10 a predictor of in-stent restenosis in stable and unstable angina patients undergoing coronary interventions? PMID- 25129274 TI - Resolution of acquired von Willebrand syndrome after transcatheter aortic valve implantation through a left transcarotid approach. PMID- 25129275 TI - Residual platelet reactivity after clopidogrel loading in ST-elevation myocardial infarction patients undergoing a delayed catheterization. Impact on long term clinical events. PMID- 25129276 TI - Transthoracic echocardiographic backscatter-based assessment of left atrial remodeling involving left atrial and ventricular fibrosis in patients with atrial fibrillation. PMID- 25129277 TI - The Anp genetic variant Rs5068 and circulating levels of natriuretic peptides in patients with chronic heart failure. PMID- 25129279 TI - Prevalence of overweight and obesity among children and adolescents is associated with urbanization in Shandong, China. PMID- 25129278 TI - Serum albumin changes and multivariate dynamic risk modelling in chronic heart failure. AB - BACKGROUND: We examined the prognostic utility of rate of change in serum albumin over time in chronic heart failure (CHF), as well as the utility of multivariate dynamic risk modelling. METHODS AND RESULTS: The survival implication of ?albumin was analysed in 232 systolic CHF patients and validated in 212 patients. A multivariate dynamic risk score predicated on the rate of change in 6 simple indices including albumin was calculated and related to mortality. In derivation patients, 50 (22%) deaths occurred over 13 months. Greater rates of decline in albumin related to higher mortality (HR 0.55, 95% CI 0.41-0.73, P<0.0001) independently, incrementally and more accurately than other covariates including baseline albumin. A rate of attenuation >0.4 g/dL/month optimally forecasted death and was associated with a 5-fold escalated risk of mortality (HR 5.13, 95% CI 2.92-9.00, P<0.0001). Similar results were seen in the validation cohort. On multivariate dynamic risk modelling, survival at 1-year worsened with higher scores-a score >= 3 was associated with a 12-fold greater risk of death than a score of 0, a 6-fold higher risk of death than a score of 1, and a 4-fold enhanced risk of mortality than a score of 2. CONCLUSION: Attenuations in serum albumin over time relate to increased mortality in CHF, and a risk model predicated on the rate of change in 6 simple indices can identify patients at a 12-fold enhanced risk of death over the coming year. PMID- 25129280 TI - Cardiovascular mortality and the financial crisis in Greece: trends and outlook. PMID- 25129281 TI - Characterisation of novel cytokines in human atherosclerotic plaque. PMID- 25129282 TI - Validation of rate of perceived exertion-based exercise training in patients with heart failure: insights from autonomic nervous system adaptations. AB - BACKGROUND: Exercise prescription in cardiac patients is based on heart rate (HR) response to exercise. How to prescribe long-term exercise training outside medically-supervised settings also considering changes in individual physical capacity over time is unknown. In this study we hypothesized that in patients with chronic heart failure (CHF) the session-rate of perceived exertion (RPE), a subjective-based training methodology, provides autonomic and functional capacity changes superimposable to those observed with HR-based Training Impulses (TRIMPi) method. METHODS: Twenty patients with stable CHF were randomized to either aerobic continuous training (ACT) or aerobic interval training (AIT) for 12 weeks. For each TRIMPi-guided exercise session, the session-RPE was recorded. By this method, internal training load (TL) is quantified by multiplying the RPE of the whole training session, using the Borg CR10-scale, by its duration. Heart rate variability (HRV), and baroreflex sensitivity (BRS) were assessed at baseline and at 3 weeks intervals. RESULTS: Significant correlations were found between TRIMPi and individual session-RPE, for both ACT and AIT (r=0.63 to 0.81), (P<0.05). The same occurred when ACT and AIT groups were pooled together (r=0.72; P<0.01). R-R interval, HRV and BRS were significantly and very highly correlated with weekly RPE-session (r(2) ranged from 0.77 to 0.97; P<0.001). A significant relationship between session-RPE and performance at the 6MWT was also found. CONCLUSIONS: Session-RPE is an easy-to-use, inexpensive and valid method for exercise prescription and health maintenance, consistent with objective physiological indices of training, that could be used for long-term physical activity in patients with CHF. PMID- 25129283 TI - In case of strict application, the third universal definition of myocardial infarction will erase takotsubo syndrome as a diagnosis. PMID- 25129284 TI - One of the causes of secondary cardiyomyopathies: diabetic cardiomyopathy. PMID- 25129285 TI - Left ventricular hypertrophy and QTc dispersion are predictors of long-term mortality in subjects with type 2 diabetes. PMID- 25129286 TI - Coronary stent fracture mechanisms and clinical implications assessed by multimodality imaging. PMID- 25129287 TI - Electrical stimulation of the renal arterial nerves does not unmask the blindness of renal denervation procedure in swine. PMID- 25129288 TI - 6-year post-PCI follow-up of a 110-year myocardial infarction patient: a case report. PMID- 25129289 TI - Cardiotoxicity: anthracyclines and long term cancer survivors. PMID- 25129290 TI - Electrocardiographic changes in young men with left-sided spontaneous pneumothorax. PMID- 25129292 TI - Atrial septal defect occluder for the distal re-entry tear in type B aortic dissection. PMID- 25129291 TI - Hemodynamic effects of Ivabradine in addition to dobutamine in patients with severe systolic dysfunction. AB - BACKGROUND: Dobutamine induced tachycardia increases myocardial oxygen consumption and impairs ventricular filling. We hypothesized that Ivabradine may be efficient to control dobutamine induced tachycardia. METHODS: We assessed the effects of Ivabradine in addition to dobutamine in stable heart failure (HF) patients (LVEF < 35%, n = 22, test population) and validated its effects in refractory cardiogenic shock patients (n = 9, validation population) with contraindication to cardiac assistance or transplant. In the test population (62 +/- 17 years, LVEF = 24 +/- 8%), systolic and diastolic function were assessed at rest and under dobutamine [10 gamma/min], before and after Ivabradine [5mg per os]. In the validation population (54 +/- 11 years, LVEF = 22 +/- 7%), Ivabradine [5mg twice a day] was added to the dobutamine infusion. RESULTS: In the test population, Ivabradine decreased heart rate [HR] at rest and during dobutamine echocardiography (-9 +/- 8 bpm, P = 0.0004). The decrease in HR was associated with a decrease in cardiac power output and an increase in diastolic duration at rest (+ 74 +/- 67 ms, P = 0.0002), and during dobutamine infusion (+ 75 +/- 67 ms, P < 0.0001). Change in LVEF during dobutamine was greater after Ivabradine treatment than before (+ 7.2 +/- 4.7% vs. + 3.6 +/- 4.2%, P = 0.002). In the validation population, Ivabradine decreased HR (-18 +/- 11 bpm, P = 0.008) and improved diastolic filling time (+ 67 +/- 42 ms, P = 0.012) without decreasing cardiac output. At 24h, Ivabradine improved systolic blood pressure (+ 9 +/- 5 mmHg, P = 0.007), daily urine output (+ 0.7 +/- 0.5L, P = 0.008), oxygen balance (DeltaScv02 = + 13 +/- 15%, P = 0.010), and NT-pro BNP (-2270 +/- 1912 pg/mL, P = 0.017). Finally, only 2/9 (22%) patients died whereas expected mortality determined from a historical cohort was 78% (P = 0.017). CONCLUSION: This pilot study demonstrates the safety and potential benefit of a HR lowering agent in cardiogenic shock. PMID- 25129293 TI - 10-year risk for atherosclerotic cardiovascular disease and coronary heart disease among Korean adults: findings from the Korean National Health and Nutrition Examination Survey 2009-2010. AB - BACKGROUND: This study examined the distribution of the 10-year risk for development of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD), and the proportion of participants eligible for lipid management, in the Korean population. METHODS: The risk was estimated using the Pooled Cohort Equations for non-Hispanic Whites and the Adult Treatment Panel (ATP) III equations. Eligibility for lipid-lowering treatment was assessed using the American College of Cardiology/American Heart Association Blood Cholesterol Guideline and the ATP III recommendation. Complex sampling design and area under the receiver operator characteristic curve (AUC) were used. RESULTS: Among 7594 ASCVD-free Korean adults, aged 40-79 years, 31.3% (men, 44.1%; women, 19%) had a 10-year risk for an ASCVD event of >= 7.5%, and 27.1% (men, 39.4%; women, 15.2%) had a 10-year risk for a CHD event of >= 10%. These proportions differed according to age groups, ranging from 6.1 to 91.9% and 8.7 to 58.7% for patients in their 40s-70s, using the ASCVD and CHD risk estimations, respectively. Overall, 78.7% of individuals remain in the same risk stratum. Those eligible for lipid management included 32.8% of the participants using the ACC/AHA Guideline and 11.9% of those using the ATP III recommendation. In discriminating ASCVD, AUCs for the ASCVD risk assessment method and the CHD risk assessment method were 0.70 and 0.64, respectively (P<0.001). CONCLUSIONS: The distribution of 10-year ASCVD and CHD risk was different according to the risk assessment methods. PMID- 25129294 TI - The electrocardiogram as a predictive tool for recovery from poor left ventricular function following coronary revascularization. PMID- 25129295 TI - Speckle tracking echocardiography in cardiac sarcoidosis. PMID- 25129296 TI - Electrical alternans due to large bilateral pleural effusion without pericardial effusion. PMID- 25129297 TI - Bosentan treatment for pulmonary arterial hypertension due to patent ductus arteriosus and Down's syndrome in an infant. PMID- 25129298 TI - Effectiveness of switching 'low responders' to prasugrel to ticagrelor after acute coronary syndrome. PMID- 25129299 TI - Removal of an intracardiac lost port-A catheter utilizing a simple low-cost method. PMID- 25129300 TI - Obesity paradox in patients with atrial fibrillation and heart failure. PMID- 25129301 TI - Are late potentials and fractionated electrocardiograms in patients with non ischemic and ischemic cardiomyopathy wholly (or partially) due to repolarization abnormalities? PMID- 25129302 TI - Testosterone levels and heart failure in obese and non-obese men. PMID- 25129303 TI - Left ventricular fibroma: what cardiac magnetic resonance imaging may add? PMID- 25129304 TI - First report of stent thrombosis after a switch therapy resulting from ticagrelor related dyspnea. PMID- 25129305 TI - Utility of intra-aortic balloon pump support for multivessel coronary artery spasm and cardiac arrest. PMID- 25129306 TI - Intra-scar perfusion heterogeneity by cardiac magnetic resonance in a porcine model of non-reperfused myocardial infarction. PMID- 25129307 TI - Renal denervation: should we still hang in there? PMID- 25129308 TI - Effects of weather on neurally mediated syncope tests. PMID- 25129309 TI - Management of oral chronic pharmacotherapy in patients hospitalized for acute decompensated heart failure. AB - Acute decompensated heart failure (ADHF) is the most common cause of cardiovascular hospitalization. The presentation is characterized by different clinical profiles due to various underlying causes, volume balance and tissue perfusion status. Currently, a variety of pharmacological therapies, including diuretics, beta-blockers, ACE-inhibitors, angiotensin receptor blockers and digoxin, are usually prescribed in order to treat chronic heart failure (HF) syndromes caused by left ventricular systolic dysfunction. Despite the large number of HF patients with frequent hospitalizations for decompensation, only a few studies have evaluated the management of oral chronic therapies in the clinical setting of ADHF. This article summarizes the information derived from the few published trials on this subject and a therapeutic approach is suggested with respect to the continuation, dose modification or suspension of oral medications. PMID- 25129310 TI - Circulating miR-222 in plasma and its potential diagnostic and prognostic value in gastric cancer. AB - Previous studies have revealed the significance of circulating microRNAs as biomarkers for cancers. The aim of this study was to detect the levels of circulating microRNA-222 (miR-222) in plasma of gastric cancer (GC) patients and evaluate its diagnostic and prognostic value. Levels of circulating miR-222 were detected by using qRT-PCR in plasma of 114 GC patients, 36 chronic atrophic gastritis (CAG) patients and 56 healthy controls. The result showed that the expression of circulating miR-222 in plasma was significantly upregulated in GC compared with CAG and healthy controls (all at P < 0.001). And its high level was significantly correlated with clinical stages (P < 0.001) and lymph nodes metastasis (P = 0.009). The receiver operating characteristics (ROC) curve analyses revealed that miR-222 had considerable diagnostic accuracy, yielded an AUC (the areas under the ROC curve) of 0.850 with 66.1 % sensitivity and 88.3 % specificity in discriminating GC from healthy controls. Moreover, Kaplan-Meier analysis demonstrated a correlation between increased circulating miR-222 level and reduced disease-free survival (P = 0.016) and overall survival (P = 0.012). In multivariate analysis stratified for known prognostic variables, circulating miR-222 was identified as an independent prognostic marker. In conclusion, our findings suggested that circulating miR-222 in plasma might be a potential and useful noninvasive biomarker for the early detection and prognosis of GC. PMID- 25129311 TI - Expression of serum survivin protein in diagnosis and prognosis of gallbladder cancer: a comparative study. AB - The role of survivin in gallbladder cancer (GBC) has not been evaluated. We investigated survivin protein expression in serum of patients with gallbladder diseases (cholelithiasis, n = 30; GBC, n = 39) and compared with healthy controls (n = 25). Clinicopathological parameters, diagnosis and prognosis of patients with GBC were correlated with the expression of serum survivin by enzyme-linked immunosorbent assay. Significantly higher (P < 0.0001) expression of survivin protein was observed in GBC as compared to cholelithiasis and control. Increased survivin expression was significantly associated with higher tumor stage (stage III vs. stage II; P < 0.0001) and cellular differentiation (poor and moderate vs. well differentiated; P < 0.0001) in GBC. No significant correlation was observed with any of the other clinico-pathological parameters studied. The cutoff value of survivin protein of 79 pg/ml with sensitivity of 81.16 % and specificity of 80 % differentiated the diseased group (cholelithiasis or GBC) from control group were as the cutoff value of 109 pg/ml differentiated GBC from cholelithiasis with a sensitivity of 82.05 % and specificity of 93.33 %. Though not significant, increased expression of survivin was associated with median overall survival (12 vs. 18 months; P = 0.05) in GBC patients. Our study suggests that survivin protein in serum could be both a useful diagnostic marker and an important prognostic factor for GBC. PMID- 25129312 TI - Diagnostic and prognostic significance of serum miR-24-3p in HBV-related hepatocellular carcinoma. AB - The aim of this study was to explore the diagnostic and prognostic value of serum microRNAs (miRNAs) in hepatitis B viral (HBV)-related hepatocellular carcinoma (HCC). We retrospectively analyzed clinical data of 84 consecutive patients with HBV-related HCC who underwent curative resection. Additionally, we enrolled 46 healthy controls and 31 patients with chronic liver disease (CLD). Serum levels of miR-155-5p, miR-24-3p, miR-490-3p, miR-210-3p, and miR-335-5p were measured. Associations of serum miRNAs with clinicopathological factors were evaluated. Receiver operating characteristic curves were established for discriminating HCC patients from CLD patients, and the area under the curve (AUC) was calculated. Overall survival (OS) and disease-free survival (DFS) were examined by the Kaplan Meier method. Prognostic factors were determined by multivariate Cox analysis. Consequently, serum miR-24-3p levels were significantly greater in HCC patients than healthy controls and CLD patients. Serum miR-24-3p was significantly associated with vascular invasion in HCC patients. Serum miR-24-3p discriminated HCC patients from CLD, with an AUC of 0.636 [95 % confidence interval (CI) 0.524 0.748]. Combined serum alpha-fetoprotein (AFP) and miR-24-3p had an increased AUC of 0.834 (95 % CI 0.745-0.923; P < 0.001). Elevated serum miR-24-3p was an independent poor prognostic factor for OS and DFS of HCC patients. In conclusion, the combination of serum miR-24-3p and AFP improves the diagnostic accuracy for HCC prediction compared to each biomarker alone. High serum miR-24-3p level is an independent predictor of poor OS and DFS in patients with HBV-related HCC. PMID- 25129313 TI - Overexpression of fibrinogen-like protein 2 induces epithelial-to-mesenchymal transition and promotes tumor progression in colorectal carcinoma. AB - The main cause of death in colorectal carcinoma (CRC) patients is tumor metastasis; however, the underlying molecular mechanisms are largely unknown. In the present study, a novel metastasis-related gene, fibrinogen-like protein 2 (FGL2), was characterized for its role in CRC metastasis and underlying molecular mechanisms. The clinical significance of FGL2 was investigated using tissue microarray analysis of samples from 82 patients with CRC. The molecular effects of FGL2 in CRC cells were determined using RNA interference and ectopic expression of FGL2. The overexpression of FGL2 was examined by immunohistochemistry in 82 CRC patients, and it was determined to be an independent predictor of overall survival (P < 0.05). The depletion of FGL2 expression inhibited tumor progression and epithelial-to-mesenchymal transition (EMT) in vitro and in vivo, while ectopic overexpression of FGL2 enhanced cell invasion and induced EMT in vitro. Our results suggest that FGL2 plays an important oncogenic role in CRC aggressiveness by inducing EMT, and FGL2 could be employed as a novel prognostic marker and effective therapeutic target for CRC. PMID- 25129314 TI - Action of nitroheterocyclic drugs against Clostridium difficile. AB - The nitroheterocyclic classes of drugs have a long history of use in treating anaerobic infections, as exemplified by metronidazole as a first-line treatment for mild-to-moderate Clostridium difficile infection (CDI). Since direct comparisons of the three major classes of nitroheterocyclic drugs (i.e. nitroimidazole, nitazoxanide and nitrofurans) and nitrosating agents against C. difficile are under-examined, in this study their actions against C. difficile were compared. Results show that whilst transient resistance occurs to metronidazole and nitazoxanide, stable resistance arises to nitrofurans upon serial passage. All compounds killed C. difficile at high concentrations in addition to the host defence nitrosating agent S-nitrosoglutathione (GSNO). This suggests that GSNO killing of C. difficile contributes to its efficacy in murine CDI. Although nitric oxide production could not be detected for the nitroheterocyclic drugs, the cellular response to metronidazole and nitrofurans has some overlap with the response to GSNO, causing significant upregulation of the hybrid-cluster protein Hcp that responds to nitrosative stress. These findings provide new insights into the action of nitroheterocyclic drugs against C. difficile. PMID- 25129316 TI - Carbapenem-resistant Enterobacter gergoviae harbouring blaKPC-2 in Brazil. PMID- 25129317 TI - Mutant prevention concentrations of pradofloxacin for susceptible and mutant strains of Escherichia coli with reduced fluoroquinolone susceptibility. AB - Pharmacodynamic and mutant prevention properties of the fluoroquinolone pradofloxacin (PRA) were measured against a set of 17 Escherichia coli strains carrying no, one or two known mutations conferring reduced fluoroquinolone susceptibility. The strains included susceptible wild-types, isogenic constructed mutants, isogenic selected mutants and clinical isolates. The effectiveness of PRA was determined with regard to preventing the selection of resistant mutants, using static and changing concentrations of drug. Ciprofloxacin was used as a reference drug. Minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of PRA for the susceptible wild-type strains were in the range 0.012-0.016mg/L and 0.2-0.3mg/L, respectively, giving a mean+/-standard deviation mutant prevention index (MPI=MPC/MIC) of 17.7+/-1.1. The mean MPI PRA of the 14 mutant strains was 19.2+/-12, and the mean MPI across all 17 strains was 18.9+/-10.8. In an in vitro kinetic model in which PRA was diluted with a half-life of 7h to mimic in vivo conditions, an initial concentration of PRA of 1.6-2.4mg/L (8-10* MPC), giving a PRA AUC/MPC ratio of 73-92, and a T>MPC of 21 23h was sufficient to prevent the selection of resistant mutants from the three susceptible wild-type strains. Dosing to reduce selection for antibiotic resistance in veterinary therapy has a role in reducing the reservoir of resistant mutants. We conclude that a level of dosing that prevents the selection of resistant mutants during therapy should be achievable in vivo. PMID- 25129315 TI - Activity of echinocandins and triazoles against a contemporary (2012) worldwide collection of yeast and moulds collected from invasive infections. AB - In this study, 1717 fungal clinical isolates causing invasive fungal infections were evaluated against nine antifungal agents using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods. The isolates comprised 1487 Candida spp., 109 Aspergillus spp., 86 non-Candida yeasts (including 52 isolates of Cryptococcus neoformans) and 35 rare moulds obtained during 2012 from 72 hospitals worldwide. Echinocandin resistance among Candida spp. was low, and resistance rates to anidulafungin, caspofungin and micafungin varied from 0.0% to 2.8% among different species. Echinocandin-resistant Candida glabrata were shown to have fks mutations (fks2 HS1 F659Y, F659del, S663F and S663P), and fluconazole resistance was also observed in those strains. One Candida krusei and one Candida dubliniensis had L701M or S645P fks1 mutations, respectively. Candida tropicalis and C. glabrata had higher fluconazole resistance rates of 6.1% and 6.9%, respectively, compared with other Candida spp. Fluconazole-resistant C. tropicalis were collected in five countries (USA, China, Germany, Belgium and Thailand). Voriconazole was active against all Candida spp., inhibiting 91.2-99.7% of isolates using species-specific breakpoints. All agents except for the echinocandins and posaconazole were active against Cr. neoformans. Triazoles were active against other yeasts [MIC90 (minimum inhibitory concentration encompassing 90% of isolates tested), 2MUg/mL]. The echinocandins and the mould-active triazoles were active against Aspergillus [MIC/MEC90 (minimum effective concentration encompassing 90% of isolates tested) range, 0.015-2MUg/mL], but the activity of these agents was limited against uncommon mould species (MIC/MEC90 range, 4MUg/mL to >16MUg/mL). PMID- 25129318 TI - Neonatal candidiasis: diagnosis, prevention, and treatment. AB - Infection with Candida species is associated with significant morbidity and mortality in infants. The incidence of Candida infection varies widely across centers, likely due to differences in practice related to modifiable risk factors such as exposure to empiric antibiotics and length of parenteral nutrition. Early diagnosis of Candida and prompt treatment with appropriate antifungal agents, such as fluconazole, amphotericin B deoxycholate, and micafungin, are critical for improved outcomes. This paper reviews the current literature relating to the prevention, diagnosis, and treatment of Candida infections in the neonatal intensive care unit. PMID- 25129319 TI - [Practical management of neonatal sepsis risk in term or near-term infants]. AB - Incidence of neonatal early-onset sepsis has dramatically declined in France from 0.65 to 0.230/00 live births in 10 years since national guidelines to detect and treat intrapartum women with group B streptococcus colonization have been adopted. However, neonatal early-onset sepsis continues to be a common healthcare burden. Group B streptococcus (GBS) remains the leading cause of bacterial infection in term or near-term infants. As a result of prevention strategies, approximately 30% of pregnant women and more than 2% of newborns are treated with systemic antibiotics. Concerns have been expressed about the safety of wide use of antibiotics such as antibiotic resistance, emergence of Escherichia coli infections, and long-term side effects due to gut microbiota modifications. New recommendations from the Centers of Disease Control in the United States and from European countries aim at improving GBS detection methods, updating algorithms for GBS intrapartum chemoprophylaxis in pregnant women, defining high-risk newborns more efficiently, and limiting biological evaluation in low-risk newborns. PMID- 25129321 TI - The variation of HVL with focal spot to chamber distance as a function of beam quality for the Pantak Therapax 150 X-ray unit and the implications on dose to water determination using the IPEMB code of practice. AB - Using a Pantak Therapax SXT 150 system HVL values for clinical beams generated with filters 4-8, were determined as a function of FCD (30-130 cm). Aluminium absorbers were placed midway between the focus and chamber with collimation to define both narrow and broad beam geometries. For filters 4-7 with broad beam geometry the HVL initially decreases as the FCD is increased from 30 cm and then increases as the FCD approaches 130 cm. In contrast filter 8 exhibits a reduction in HVL with increasing FCD attributed to the decreasing influence of absorber scatter. With narrow beam geometry the HVL of filter 4 increases as the FCD is increased. For other filters the HVL variation is similar to that for the broader beam albeit that for a given FCD the HVL is smaller, a consequence of reduced absorber scatter. Monte Carlo BEAMnrc simulations of filter 4-8 beams demonstrated a quality dependent air attenuation effect associated with an increase in HVL for lower quality beams with increasing FCD. Thus for the beams investigated in this work the variation of HVL with FCD can be interpreted in terms of the competing influences of absorber scatter, which tends to decrease the measured HVL, and a quality dependent in air attenuation that tends to increase the HVL with increasing FCD. In terms of an absorbed dose determination it is shown that changes of HVL with FCD resulted in variations of D w,z = 0 < +/ 0.5 %. PMID- 25129320 TI - [Overdose or hypersensitivity to vitamin D?]. AB - Vitamin D intoxication with severe hypercalcemia is rare in the neonatal and infancy period. Through nine cases of hypercalcemia, secondary to taking 600,000 units of vitamin D (Sterogyl((r))), a review of vitamin D requirements and possible mechanisms of toxicity including hypersensitivity to this vitamin will be discussed. We report nine cases of babies admitted to our department between the ages of 25 and 105 days for treatment of severe dehydration. The pregnancies were normal, with no incidents at delivery. Clinical signs were dominated by weight loss, vomiting, and fever. Examination on admission revealed dehydration whose degree ranged from 8 to 15% with preserved diuresis and loss weight between 100 and 1100 g. Laboratory tests objectified hypercalcemia between 113 and 235mg/L, hypercalciuria (urinary calcium/creatinine mmol/mmol >0.5), and a low level of parathyroid hormone. The vitamin D values in nine patients were toxic (344-749 nmol/L; normal >50 nmol/L; toxicity if >250 nmol/L). Abdominal ultrasound objectified renal nephrocalcinosis in seven patients. The DNA study, performed in eight patients, did not reveal a mutation of the vitamin D 24 hydroxylase gene (CYP24A1). The treatment consisted of intravenous rehydration with treatment of hypercalcemia (diuretics and corticosteroids). Serum calcium returned to the normal range within 4-50 days, with weight gain progressively over the following weeks. The follow-up (2 years for the oldest case) showed the persistence of images of nephrocalcinosis. Genetic susceptibility and metabolic differences appear to modulate the threshold of vitamin D toxicity. However, respect for recommended doses, recognized as safe in a large study population, reduces the risk of toxicity. PMID- 25129322 TI - [Acute stent thrombosis and reverse transient left ventricular dilatation after performing a single-photon emission computed tomography myocardial perfusion]. AB - A 63-year-old male patient with a history of stent implantation in the left anterior descending three months before. Due to the presentation of vegetative symptoms, he was referred for gated-SPECT myocardial perfusion. During acquisition of the resting images he presented chest pain and ST segment elevation, so that urgent cardiac catheterization was performed, showing stent thrombosis. Rest perfusion imaging showed a defect in anterior and apical perfusion, more severe and extensive than in the stress images, with striking left ventricular dilatation and a fall in the ejection fraction related to the acute ischemia phenomenon. Intense exercise is associated with a transient activation of the coagulation system and hemodynamic changes that might induce thrombosis, especially in recently implanted coronary stents that probably still have not become completely endothelialized. PMID- 25129323 TI - The structure and demographic correlates of cancer fear. AB - BACKGROUND: Cancer is often described as the 'number one' health fear, but little is known about whether this affects quality of life by translating into high levels of worry or distress in everyday life, or which population groups are most affected. This study examined the prevalence of three components of cancer fear in a large community sample in the UK and explored associations with demographic characteristics. METHODS: Questions on cancer fear were included in a survey mailed to a community sample of adults (n = 13,351; 55-64 years). Three items from a standard measure of cancer fear assessed: i) whether cancer was feared more than other diseases, ii) whether thinking about cancer caused discomfort, and iii) whether cancer worry was experienced frequently. Gender, marital status, education, and ethnicity were assessed with simple questions. Anxiety was assessed with the brief STAI and a standard measure of self-rated health was included. RESULTS: Questionnaire return rate was 60% (7,971/13,351). The majority of respondents agreed or strongly agreed that they feared cancer more than other diseases (59%), and felt uncomfortable thinking about it (52%), and a quarter (25%) worried a lot about cancer. All items were significantly inter-correlated (r = .35 to .42, p's < .001), and correlated with general anxiety (r = .16 to .28, p's < .001) and self-rated health (r = -.07 to -.16, p's < .001). In multivariable analyses including anxiety and general health, all cancer fear indicators were significantly higher in women (ORs between 1.15 and 1.48), respondents with lower education (ORs between 1.40 and 1.66), and those with higher general anxiety (ORs between 1.50 and 2.11). Ethnic minority respondents (n = 285; 4.4%) reported more worry (OR: 1.85). CONCLUSIONS: More than half of this older adult sample in the UK had cancer as greatest health fear and this was associated with feeling uncomfortable thinking about it and worrying more about it. Women and respondents with less education or from ethnic minority backgrounds were disproportionately affected by cancer fear. General anxiety and poor health were associated with cancer fear but did not explain the demographic differences. PMID- 25129324 TI - Radioactive and chemical contamination of the water resources in the former uranium mining and milling sites of Mailuu Suu (Kyrgyzstan). AB - An assessment of the radioactive and chemical contamination of the water resources at the former uranium mines and processing sites of Mailuu-Suu, in Kyrgyzstan, was carried out. A large number of water samples were collected from the drinking water distribution system (DWDS), rivers, shallow aquifers and drainage water from the mine tailings. Radionuclides and trace metal contents in water from the DWDS were low in general, but were extremely high for Fe, Al and Mn. These elements were associated with the particle fractions in the water and strongly correlated with high turbidity levels. Overall, these results suggest that water from the DWDS does not represent a serious radiological hazard to the Mailuu Suu population. However, due to the high turbidities and contents of some elements, this water is not good quality drinking water. Water from artesian and dug wells were characterized by elevated levels of U (up to 10 MUg/L) and some trace elements (e.g. As, Se, Cr, V and F) and anions (e.g. Cl(-), NO3(-), SO4(2 )). In two artesian wells, the WHO guideline value of 10 MUg/L for As in water was exceeded. As the artesian wells are used as a source of drinking water by a large number of households, special care should be taken in order to stay within the WHO recommended guidelines. Drainage water from the mine tailings was as expected highly contaminated with many chemicals (e.g. As) and radioactive contaminants (e.g. U). The concentrations of U were more than 200 times the WHO guideline value of 30 MUg/L for U in drinking water. A large variation in (234)U/(238)U isotopic ratios in water was observed, with values near equilibrium at the mine tailings and far from equilibrium outside this area (reaching ratios of 2.3 in the artesian well). This result highlights the potential use of this ratio as an indicator of the origin of U contamination in Mailuu Suu. PMID- 25129326 TI - Obesity: a certain and avoidable cause of cancer. PMID- 25129325 TI - Gastric residual evaluation in preterm neonates: a useful monitoring technique or a hindrance? AB - It is routine practice in most neonatal intensive care units to measure the volume and color of gastric residuals (GRs) prior to enteral bolus feedings in preterm very low birth weight infants. However, there is paucity of evidence supporting the routine use of this technique. Moreover, owing to the lack of uniform standards in the management of GRs, wide variations exist as to what constitutes significant GR volume, the importance of GR color and frequency of GR evaluation, and the color or volume standards that dictate discarding or returning GRs. The presence of large GR volumes or green-colored residuals prior to feeding often prompts subsequent feedings to be withheld or reduced because of possible necrotizing enterocolitis resulting in delays in enteral feeding. Cessation or delays in enteral feeding may result in extrauterine growth restriction, a known risk factor for poor neurodevelopmental and growth outcomes in preterm very low birth weight infants. Although some neonatal intensive care units are abandoning the practice of routine GR evaluation, little evidence exists to support the discontinuation or continuation of this practice. This review summarizes the current state of GR evaluation and underlines the need for a scientific basis to either support or refute the routine evaluation of GRs. PMID- 25129327 TI - Africa's child demographics and the world's future. PMID- 25129328 TI - Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. AB - BACKGROUND: High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS: With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS: 5.24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1.62, 99% CI 1.56-1.69; p<0.0001), gallbladder (1.31, 1.12-1.52; p<0.0001), kidney (1.25, 1.17-1.33; p<0.0001), cervix (1.10, 1.03 1.17; p=0.00035), thyroid (1.09, 1.00-1.19; p=0.0088), and leukaemia (1.09, 1.05 1.13; p<=0.0001). BMI was positively associated with liver (1.19, 1.12-1.27), colon (1.10, 1.07-1.13), ovarian (1.09, 1.04-1.14), and postmenopausal breast cancers (1.05, 1.03-1.07) overall (all p<0.0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0.98, 0.95-1.00; premenopausal breast cancer 0.89, 0.86-0.92) and in never-smokers (prostate 0.96, 0.93-0.99; premenopausal breast cancer 0.89, 0.85 0.94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0.99, 0.93-1.05; oral cavity 1.07, 0.91-1.26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION: BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING: National Institute for Health Research, Wellcome Trust, and Medical Research Council. PMID- 25129330 TI - Finding the Twitter users who stood with Wendy. AB - OBJECTIVE: I examine Twitter discussion regarding the Texas omnibus abortion restriction bill before, during and after Wendy Davis' filibuster in summer 2013. This critical moment precipitated wide public discussion of abortion. Digital records allow me to characterize the spatial distribution of participants in Texas and the United States and estimate the proportion of participants who were Texans. STUDY DESIGN: Building a dataset based on all hashtags associated with the bill between June 19th and July 14th, 2013, I use GPS locations and text descriptions of locations to classify users by county of residence. Mapping tweets from accounts within the continental United States by day, I describe the residential composition of the conversation in total and over time. Using indirect estimation, I compute an estimate of the number of Texans who participated. RESULTS: About 1.66 million tweets were sent using hashtags associated with the bill from 399,081 user accounts. I estimate counties of residence for 160,954 participants (40.3%). An estimated 115,500 participants (29%) were Texans, and Texans sent an estimated 48.8% of all tweets. Tweets were sent from users estimated to live in every region of Texas, including 189 of Texas' 254 counties. Texans tweeted more than non-Texans on every day except the filibuster and the day after. CONCLUSION: The analysis measures real-life responses to proposed abortion restrictions from people across Texas and the United States. It demonstrates that Twitter users from across Texas counties opposed HB2 by describing the geographical range of US and Texan abortion rights supporters on Twitter. IMPLICATIONS: The Twitter discussion surrounding Wendy Davis' filibuster revealed a geographically diverse population of individuals who strongly oppose abortion restrictions. Texans from across the state were among those who actively voiced opposition. Identifying rights supporters through online behavior may present a new way of classifying individuals' orientations regarding abortion rights. PMID- 25129329 TI - Unmet demand for highly effective postpartum contraception in Texas. AB - OBJECTIVES: We aimed to assess women's contraceptive preferences and use in the first 6 months after delivery. The postpartum period represents a key opportunity for women to learn about and obtain effective contraception, especially since 50% of unintended pregnancies to parous women occur within 2 years of a previous birth. METHODS: We conducted a prospective cohort study of 800 postpartum women recruited from three hospitals in Austin and El Paso, TX. Women aged 18-44 who wanted to delay childbearing for at least 24 months were eligible for the study and completed interviews following delivery and at 3 and 6 months postpartum. Participants were asked about the contraceptive method they were currently using and the method they would prefer to use at 6 months after delivery. RESULTS: At 6 months postpartum, 13% of women were using an intrauterine device or implant, and 17% were sterilized or had a partner who had had a vasectomy. Twenty-four percent were using hormonal methods, and 45% relied on less effective methods, mainly condoms and withdrawal. Yet 44% reported that they would prefer to be using sterilization, and 34% would prefer to be using long-acting reversible contraception (LARC). CONCLUSIONS: This study shows a considerable preference for LARC and permanent methods at 6 months postpartum. However, there is a marked discordance between women's method preference and actual use, indicating substantial unmet demand for highly effective methods of contraception. IMPLICATIONS: In two Texas cities, many more women preferred long-acting and permanent contraceptive methods (LAPM) than were able to access these methods at 6 months postpartum. Women's contraceptive needs could be better met by counseling about all methods, by reducing cost barriers and by making LAPM available at more sites. PMID- 25129332 TI - Antibacterial activities of nemonoxacin against clinical isolates of Staphylococcus aureus: an in vitro comparison with three fluoroquinolones. AB - In comparison with ciprofloxacin, levofloxacin and moxifloxacin, antimicrobial activity of nemonoxacin against ciprofloxacin-susceptible/-resistant methicillin susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) was determined with the availability to select resistant mutants evaluated. Minimum inhibitory concentrations and mutant prevention concentrations of quinolones were determined by agar dilution method, that concentrated bacterial cells were spread onto Mueller-Hinton agar plates containing antibacterials at different concentrations. Selection index (SI) was calculated. Minimum inhibitory concentration and mutant prevention concentration of nemonoxacin were 0.063 and 0.25 MUg/mL for ciprofloxacin-susceptible MSSA and those were 0.5 and 4.0 MUg/mL for ciprofloxacin-resistant MSSA, lower than observations of three fluoroquinolones distinctly. SI of nemonoxacin and moxifloxacin were similar, with narrower mutant selective window than levofloxacin and ciprofloxacin. Minimum inhibitory concentration and mutant prevention concentration of nemonoxacin were 0.25 and 2.0 MUg/mL for ciprofloxacin-susceptible MRSA, which were 0.5 and 16.0 MUg/mL for ciprofloxacin resistant MRSA. Values were lower than those determined from fluoroquinolones. Nemonoxacin presents good antimicrobial activity against clinical isolates of S. aureus, especially for ciprofloxacin-resistant strains. But stepwise mutant accumulation of ciprofloxacin-resistant MRSA can be hardly inhibited by nemonoxacin with pharmacokinetic parameters considered. PMID- 25129331 TI - Colorectal cancer with potentially resectable hepatic metastases: optimizing treatment. AB - Colorectal cancer is a common malignancy and often presents with synchronous or metachronous distant spread. For patients with hepatic metastases, resection is the principal curative option. Liberalization of the indications for hepatic resection has introduced a number of challenges related to the size, distribution, and number of metastases as well as the condition of the future liver remnant. Advances in systemic therapy have solidified its role as both an important adjunct to surgery and also for many patients as a mechanism to facilitate resection. In patients whose disease is marginally resectable as a consequence of the distribution of hepatic lesions that precludes complete resection or out of concern for the future liver remnant, a number of strategies have been advocated, including prehepatectomy systemic therapy, staged surgical approaches, ablative technologies, and preoperative portal vein embolization. It is the purpose of this review to discuss ways in which to optimize the treatment of patients with potentially resectable disease, specifically those who are judged to have "borderline" resectable situations. PMID- 25129333 TI - Providing Rapid Out of Hospital Acute Cardiovascular Treatment 3 (PROACT-3). AB - BACKGROUND: The outcomes of acute cardiovascular symptom presentations are potentially modifiable with the use of biomarkers to accelerate accurate diagnosis. This randomized trial tested troponin and B-type natriuretic peptide before hospital guidance in patients with acute cardiovascular symptoms. METHODS: Patients with either chest pain or shortness of breath were randomized to usual care or biomarkers analyzed using a point-of-care device in the ambulance. The primary end point was time to final disposition (discharge from the emergency department or admission to hospital). The trial was stopped prematurely because of less than expected enrollment of patients of interest and no difference in the primary end point. RESULTS: We randomized 491 patients; 480 formed the final cohort. Patients were 49% male; median age 70 years; 42% had previous acute coronary syndrome; and 28% diabetes. The B-type natriuretic peptide level before hospital arrival was >= 100 pg/mL in 36.4%. Troponin was > 0.03 ng/mL in 13.4%; 3.6% had troponin > 0.1 ng/mL. After adjudication, 16% had acute coronary syndrome, 6.5% acute heart failure, 3.3% angina, and 74.2% another diagnosis. The primary end point was 9.2 (interquartile range, 7.3-11.1) hours in the biomarker group and 8.8 (interquartile range, 6.3-12.1) hours in the usual care group (P = 0.6). None died in the ambulance or in the emergency department: all-cause 30-day mortality was 2.1% (usual care) and 1.7% (biomarker). CONCLUSIONS: To our knowledge, this is the first randomized trial of biomarkers before hospital arrival to guide emergency management of suspected acute cardiovascular disease which showed no benefit and was terminated early because of futility. The results have important implications for the use of biomarkers in emergency management of heart disease and for the design of future randomized trials on this important topic. PMID- 25129334 TI - Case report: protein-losing enteropathy caused by Mesocestoides vogae (syn. M. corti) in a dog. AB - An eight-year-old, neutered, female Shetland Sheepdog presented with a 6-week history of small intestinal diarrhea. Regenerative anemia, hypoproteinemia, and an increased plasma C-reactive protein concentration were detected on blood examination. Fecal examination and abdominal radiography were unremarkable. Abdominal ultrasonography showed diffusely hyperechoic mucosa in the small intestine. Gastroduodenoscopy, performed under general anesthesia, revealed mucosal edema and increased granularity in the duodenum and jejunum. Histopathological examination of the endoscopically biopsied small intestinal mucosa revealed tapeworm infection. A single administration of a combined anthelmintic drug (5mg/kg praziquantel, 14.4 mg/kg pyrantel pamoate, and 15 mg/kg febantel) was successful for deworming, and the dog fully recovered. The parasites were removed from stored frozen duodenal mucosa and morphologically identified as Mesocestoides sp. immature adult worms. Mitochondrial (mt) 12S rDNA and mt cytochrome c oxide subunit 1 genes were amplified from the parasites. DNA sequence analysis showed that the genes shared 100% identity with those of reported M. vogae (syn. M. corti). This is the first reported case of protein losing enteropathy caused by M. vogae in a dog. PMID- 25129335 TI - Evaluation of a novel dried blood spot collection device (HemaSpotTM) to test blood samples collected from dogs for antibodies to Leishmania infantum. AB - Collection of blood samples from veterinary and wildlife patients is often challenging because the samples have to be collected on farm or in the wild under various environmental conditions. This poses many technical problems associated with venipuncture materials, their safe use and disposal, transportation and processing of collected samples. Dried blood spot (DBS) sample collection techniques offer a simple and practical alternative to traditional blood collection methods to obtain blood samples from animals for parasite antibody evaluation. The DBS collection devices are compact, simple to use, and are particularly useful for large number of samples. Additionally, DBS samples take up less space and they are easier to transport than traditional venipuncture collected blood samples. Visceral leishmaniasis (VL) is a potentially fatal parasitic disease of dogs and humans and it is frequently diagnosed by antibody tests. Immunochromatographic tests (ICT) for antibodies to Leishmania infantum are commercially available for dogs and they produce qualitative results in minutes. Measurement of canine antibodies to L. infantum with the ICT using traditional venipuncture has been validated previously, but the use of DBS samples has not been evaluated using this method. The purpose of the present study was to determine the ability of DBS samples to detect antibodies to L. infantum in dogs using a commercial ICT assay. One hundred plasma samples from dogs experimentally infected with the LIVT-1 strain of L. infantum were collected by venipuncture and frozen. Individual samples were thawed, and then 80 MUl plasma (2 drops) was aliquotted onto the 8-spoked disk pad on individual DBS sample collection devices (HemaSpotTM, Spot-On Sciences, Austin, TX), dried, and stored in the dark at room temperature. After one month and six months, respectively, 2 spokes of the 8 spokes of the disk pad of each DBS sample were removed and eluted in 200 MUl PBS. The eluate was used to test for antibodies in the ICT and compared to ICT results using thawed plasma (same initial source). Sensitivity and specificity of the ICT using DBS were determined by using ICT results from traditional blood collection samples for comparison. After 1 month, DBS samples showed 100% sensitivity and specificity when compared to ICT results on thawed plasma samples collected by traditional venipuncture. After six months storage at room temperature, DBS samples demonstrated 79% sensitivity and 100% specificity compared to traditional blood collection. Results from this study indicate that dried blood spot collection may be a useful tool for screening dogs for antibodies to L. infantum with the ICT assay. PMID- 25129336 TI - DNA fluorescence shift sensor: a rapid method for the detection of DNA hybridization using silver nanoclusters. AB - DNA-templated silver nanoclusters (AgNC) are a class of subnanometer sized fluorophores with good photostability and brightness. It has been applied as a diagnostic tool mainly for deoxyribonucleic acid (DNA) detection. Integration of DNA oligomers to generate AgNCs is interesting as varying DNA sequences can result in different fluorescence spectra. This allows a simple fluorescence shifting effect to occur upon DNA hybridization with the hybridization efficiency being a pronominal factor for successful shifting. The ability to shift the fluorescence spectra as a result of hybridization overcomes the issue of background intensities in most fluorescent based assays. Here we describe an optimized method for the detection of single-stranded and double-stranded synthetic forkhead box P3 (FOXP3) target by hybridization with the DNA fluorescence shift sensor. The system forms a three-way junction by successful hybridization of AgNC, G-rich strand (G-rich) to the target DNA, which generated a shift in fluorescence spectra with a marked increase in fluorescence intensity. The DNA fluorescence shift sensor presents a rapid and specific alternative to conventional DNA detection. PMID- 25129337 TI - Electrodialytic remediation of polychlorinated biphenyls contaminated soil with iron nanoparticles and two different surfactants. AB - Polychlorinated biphenyls (PCB) are persistent organic pollutants (POP) that strongly adsorb in soils and sediments. There is a need to develop new and cost effective solutions for the remediation of PCB contaminated soils. The suspended electrodialytic remediation combined with zero valent iron nanoparticles (nZVI) could be a competitive alternative to the commonly adapted solutions of incineration or landfilling. Surfactants can enhance the PCB desorption, dechlorination, and the contaminated soil cleanup. In this work, two different surfactants (saponin and Tween 80) were tested to enhance PCB desorption and removal from a soil sampled at a polluted site, in a two-compartment cell where the soil was stirred in a slurry with 1% surfactant, 10mL of nZVI commercial suspension, and a voltage gradient of 1Vcm(-1). The highest PCB removal was obtained with saponin. Higher chlorinated PCB congeners (penta, hexa, hepta and octachlorobiphenyl) showed removal percentages between 9% and 96%, and the congeners with highest removal were PCB138, PCB153 and PCB180. The use of low level direct current enhanced PCB removal, especially with saponin. Electrodechlorination of PCB with surfactants and nZVI showed encouraging tendencies and a base is thus formed for further optimization towards a new method for remediation of PCB polluted soils. PMID- 25129338 TI - Impact of alcohols on the formation and stability of protein-stabilized nanoemulsions. AB - Nanoemulsions are increasingly being used for encapsulation, protection, and delivery of bioactive lipids, however, their formation from natural emulsifiers is still challenging. We investigated the impact of alcohol on the formation and stability of protein-stabilized oil-in-water nanoemulsions prepared by high pressure homogenization. The influence of different alcohols (ethanol, 1 propanol, and 1-butanol) at various concentrations (0-25% w/w) on the formation and stability of emulsions stabilized by sodium caseinate, whey protein isolate, and fish gelatin was investigated. The mean particle diameter decreased with increasing alcohol concentrations from 0 to 10%w/w, but extensive droplet aggregation occurred at higher levels. This phenomenon was attributed to enhanced protein-protein interactions between the adsorbed emulsifier molecules in the presence of alcohol leading to droplet flocculation. The smallest droplets (d<100nm) were obtained when 10%w/w 1-butanol was added to sodium caseinate stabilized nanoemulsions, but relatively small droplets (d<150nm) could also be obtained in the presence of a food-grade alcohol (ethanol). This study demonstrated that alcohol addition might be a useful tool for producing protein stabilized nanoemulsions suitable for use as delivery systems of lipophilic bioactive agents. PMID- 25129339 TI - Short-term impact of pictorial posters and a crash course on radiographic errors for improving the quality of paediatric chest radiographs in an unsupervised unit - a pilot study for quality-assurance outreach. AB - BACKGROUND: Chest radiography is the most commonly performed diagnostic X-ray examination. The radiation dose to the patient for this examination is relatively low but because of its frequent use, the contribution to the collective dose is considerable. Optimized image quality not only allows for more accurate diagnosis but also supports radiation protection, which is particularly important in children. OBJECTIVE: To determine whether the introduction of a poster of technical errors in paediatric radiography accompanied by a short lecture (crash course) for radiographers on common errors can sustainably decrease the number and rate of these errors in an unsupervised radiology department (without a paediatric-trained radiologist or paediatric-trained radiography personnel). MATERIALS AND METHODS: We conducted a pilot study for quality-assurance outreach, with retrospective and prospective components, in the paediatric radiology department of a teaching hospital. The technical errors in frontal chest radiographs performed in the unit were assessed by quality-assurance analysis using a customized tick-sheet. The review was performed before and after an intervention that involved a half-hour crash course and poster displays in the department. We compared the rate of technical errors made before and after the intervention. RESULTS: There was statistically significant improvement in quality of radiographs (P < 0.0083) performed immediately after the intervention. There was a statistically significant decline in the quality of radiographs performed >2 months after the intervention. CONCLUSION: A simple intervention of a crash course and poster placement resulted in improved quality of paediatric chest radiographs. A decline in quality after 2 months suggests the need to repeat this or another type of intervention regularly. PMID- 25129340 TI - MR Imaging in a case of severe anorexia nervosa: the 'flip-flop' effect. AB - We report an MR imaging phenomenon that can lead to misinterpretation. The unique appearance of the soft tissues and bone marrow in a 19-year-old severely malnourished woman with anorexia nervosa raised concerns about technical failure or systemic pathology. Due to extreme fat depletion, the T1-weighted images appeared to be fat-suppressed and the fat-suppressed fluid-sensitive images appeared to be non-fat-suppressed ("flip-flopped"). Failure to recognize the influence of a patient's overall nutritional status on MR images may cause confusion and misdiagnosis. PMID- 25129341 TI - Assessing response in breast cancer with dynamic contrast-enhanced magnetic resonance imaging: are signal intensity-time curves adequate? AB - Quantitative DCE-MRI parameters including K(trans) (transfer constant min(-1)) can predict both response and outcome in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Quantitative methods are time-consuming to calculate, requiring expensive software and interpretive expertise. For diagnostic purposes, signal intensity-time curves (SITCs) are used for tissue characterisation. In this study, we compare the ability of NAC-related changes in SITCs with K(trans) to predict response and outcomes. 73 women with primary breast cancer underwent DCE-MRI studies before and after two cycles of NAC. Patients received anthracycline and/or docetaxel-based chemotherapy. At completion of NAC, patients had local treatment with surgery & radiotherapy and further systemic treatments. SITCs for paired DCE-MRI studies were visually scored using a five-curve type classification schema encompassing wash-in and wash-out phases and correlated with K(trans) values and to the endpoints of pathological response, OS and DFS. 58 paired patients studies were evaluable. The median size by MRI measurement for 52 tumours was 38 mm (range 17-86 mm) at baseline and 26 mm (range 10-85 mm) after two cycles of NAC. Median baseline K(trans) (min(-1)) was 0.214 (range 0.085-0.469), and post-two cycles of NAC was 0.128 (range 0.013-0.603). SITC shapes were significantly related to K(trans) values both before (chi (2) = 43.3, P = 0.000) and after two cycles of NAC (chi (2) = 60.5, P = 0.000). Changes in curve shapes were significantly related to changes in K(trans) (chi (2) = 53.5, P = 0.000). Changes in curve shape were significantly correlated with clinical (P = 0.005) and pathological response (P = 0.005). Reductions in curve shape of >=1 point were significant for overall improved survival using Kaplan-Meier analysis with a 5-year OS of 80.9 versus 68.6 % (P = 0.048). SITCs require no special software to generate and provide a useful method of assessing the effectiveness of NAC for primary breast cancer. PMID- 25129342 TI - Transcriptional repression of ER through hMAPK dependent histone deacetylation by class I HDACs. AB - Anti-estrogen therapies are not effective in ER- breast cancers, thus identifying mechanisms underlying lack of ER expression in ER- breast cancers is imperative. We have previously demonstrated that hyperactivation of MAPK (hMAPK) downstream of overexpressed EGFR or overexpression/amplification of Her2 represses ER protein and mRNA expression. Abrogation of hMAPK in ER- breast cancer cell lines and primary cultures causes re-expression of ER and restoration of anti-estrogen responses. This study was performed to identify mechanisms of hMAPK-induced transcriptional repression of ER. We found that ER promoter activity is significantly reduced in the presence of hMAPK signaling, yet did not identify specific promoter sequences responsible for this repression. We performed an epigenetic compound screen in an ER- breast cancer cell line that expresses hMAPK yet does not exhibit ER promoter hypermethylation. A number of HDAC inhibitors were identified and confirmed to modulate ER expression and estrogen signaling in multiple ER- cell lines and tumor samples lacking ER promoter methylation. siRNA mediated knockdown of HDACs 1, 2, and 3 reversed the mRNA repression in multiple breast cancer cell lines and primary cultures and ER promoter-associated histone acetylation increased following MAPK inhibition. These data implicate histone deacetylation downstream of hMAPK in the observed ER mRNA repression associated with hMAPK. Importantly, histone deacetylation appears to be a common mechanism in the transcriptional repression of ER between ER- breast cancers with or without ER promoter hypermethylation. PMID- 25129343 TI - High NR2F2 transcript level is associated with increased survival and its expression inhibits TGF-beta-dependent epithelial-mesenchymal transition in breast cancer. AB - NR2F2, a member of nuclear receptor subfamily 2, was shown to be associated with cancer, but its role in breast malignancy remains unclear. In this study, we aimed to explore the function of NR2F2 in breast cancer. We browsed GEO and TCGA databases and used Kaplan-Meier survival analysis to explore the association between NR2F2 transcript level and patient survival in breast cancer. NR2F2 expression in breast cancer tissues was evaluated by immunohistochemistry staining. NR2F2-related functions and its role in Epithelial-Mesenchymal Transition (EMT) were predicted by Gene Set Enrichment Analysis (GSEA) and validated by in vitro assays with NR2F2 knockdown MDA-MB231 and MCF7 cells. We found high NR2F2 transcript level was correlated with favorable overall survival and distant metastasis-free survival. Positive rate of NR2F2 protein tended to be decreased with the progression of malignancy. Results of in vitro migration and invasion assays suggested NR2F2's potential in inhibiting invasiveness. NR2F2 was predicted to be negatively linked with EMT and TGF-beta-pathway related genes, which was supported by observation of EMT-like morphology and changes in EMT markers E-cadherin and Slug. Additionally, we found TGF-beta inhibited the expression of NR2F2. GSEA also predicted that NR2F2 could be inversely associated with chemoresistance, which was verified by results of in vitro growth inhibition assays using chemotherapeutic agents. Our results demonstrated high NR2F2 transcript level was associated with favorable clinical outcome, which might be due to NR2F2's inhibitory effect on TGF-beta-dependent EMT and its role in inhibiting chemoresistance. PMID- 25129344 TI - Ki67 measured in metastatic tissue and prognosis in patients with advanced breast cancer. AB - The purpose of this study is to determine the prognostic role of Ki67 evaluated in relapse biopsies from patients with metastatic breast cancer (MBC). Two hundred and ten patients diagnosed with MBC in Stockholm, Sweden between 1998 and 2009 and with Ki67 assessed at time of first systemic relapse (mKi67) were retrospectively identified and divided into two groups according to mKi67 fraction (low <=20 %, high >20 %). Post-relapse survival was compared between the groups using Kaplan-Meier and Cox regression methods. Death rate as function of continuous mKi67 was also evaluated. Furthermore, the prognostic role of intra individual change in Ki67 between primary tumor and matched metastasis was explored by Kaplan-Meier plots. One hundred and twenty-five patients had low and 85 had high mKi67. Median survival was 25 and 17 months in low- and high-mKi67 group, respectively [hazard ratio (HR) 0.69, 95 % confidence intervals (CI) 0.51 0.92, P = 0.01]. In a multivariate model adjusted for prognostic confounders, low mKi67 showed a non-significant trend toward better survival (HR 0.85, 95 %CI 0.62 1.16, P = 0.30). Nevertheless, mKi67 independently correlated with survival when compared with primary tumor proliferation (HR 0.56, 95 %CI 0.38-0.81, P = 0.002). The 2-year death rate steeply increased as mKi67 increased. Moreover, the change from high in primary tumor to low in metastasis significantly correlated with longer survival when compared with stable Ki67 levels (HR 0.48, 95 %CI 0.31-0.76, P = 0.002). In this cohort of MBC patients, mKi67 inversely but not independently correlated with survival. However, a significant association between mKi67 and survival was shown regardless of primary tumor proliferation. PMID- 25129345 TI - Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. AB - The aim of this study is to estimate the frequency of pathologic complete response (pCR) after neoadjuvant treatment with cisplatin chemotherapy in women with breast cancer and a BRCA1 mutation. One hundred and seven women with breast cancer and a BRCA1 mutation, who were diagnosed with stage I to III breast cancer between December 2006 and June 2014, were treated with cisplatin 75 mg/m(2) every 3 weeks for four cycles, followed by mastectomy and conventional chemotherapy. Information was collected on clinical stage, grade, hormone receptor status, and Her2neu status prior to treatment. pCR was determined by review of surgical specimens. One hundred and seven patients were enrolled in the study, including 93 patients who were treated for first primary breast cancer and 14 patients who had previously received treatment for a prior cancer. A pCR was observed in 65 of the 107 patients (61 %). Platinum-based chemotherapy is effective in a high proportion of patients with BRCA1-associated breast cancer. PMID- 25129347 TI - The failed first metatarsophalangeal joint implant arthroplasty. AB - Chronic pain in a first metatarsophalangeal implant arthroplasty can be early or late, and may be due to infection or implant failure. Although excisional arthroplasty can be considered, the most predictable result will come from arthrodesis. Conversion of a failed implant arthroplasty to fusion will usually require structural bone graft, with slower healing times than primary fusion. PMID- 25129346 TI - Abrogating phosphorylation of eIF4B is required for EGFR and mTOR inhibitor synergy in triple-negative breast cancer. AB - Triple-negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive disease. They have a high rate of relapse and often develop resistance to standard chemotherapy. Many TNBCs have elevated epidermal growth factor receptor (EGFR) but are resistant to EGFR inhibitors as monotherapy. In this study, we sought to find a combination therapy that could sensitize TNBC to EGFR inhibitors. Phospho-mass spectrometry was performed on the TNBC cell line, BT20, treated with 0.5 MUM gefitinib. Immunoblotting measured protein levels and phosphorylation. Colony formation and growth assays analyzed the treatment on cell proliferation, while MTT assays determined the synergistic effect of inhibitor combination. A Dual-Luciferase reporter gene plasmid measured translation. All statistical analysis was done on CalucuSyn and GraphPad Prism using ANOVAs. Phospho-proteomics identified the mTOR pathway to be of interest in EGFR inhibitor resistance. In our studies, combining gefitinib and temsirolimus decreased cell growth and survival in a synergistic manner. Our data identified eIF4B, as a potentially key fragile point in EGFR and mTOR inhibitor synergy. Decreased eIF4B phosphorylation correlated with drops in growth, viability, clonogenic survival, and cap-dependent translation. Taken together, these data suggest EGFR and mTOR inhibitors abrogate growth, viability, and survival via disruption of eIF4B phosphorylation leading to decreased translation in TNBC cell lines. Further, including an mTOR inhibitor along with an EGFR inhibitor in TNBC with increased EGFR expression should be further explored. Additionally, translational regulation may play an important role in regulating EGFR and mTOR inhibitor synergy and warrant further investigation. PMID- 25129348 TI - Pain after cheilectomy of the first metatarsophalangeal joint: diagnosis and management. AB - Cheilectomy is commonly performed for osteoarthritis of the first metatarsophalangeal joint and generally has a successful outcome and high rate of patient satisfaction over the short to medium term. Despite the relatively good results achieved in most cases, a proportion of patients have ongoing pain after cheilectomy. This article outlines the potential causes of ongoing pain, including progression of osteoarthritis, neuralgic symptoms, and transfer metatarsalgia. Management strategies for treating the ongoing symptoms are discussed. PMID- 25129349 TI - Deceptions in hallux valgus: what to look for to limit failures. AB - The treatment of hallux valgus depends on multiple factors, including clinical examination, patient considerations, clinical findings, radiographic assessment, and surgeon preference. Appropriate procedure selection and proper technique will usually result in good-to-excellent outcomes. Complications following hallux valgus correction include recurrence, transfer metatarsalgia, avascular necrosis, hallux varus, and nonunion and malunion of metatarsal osteotomies. In order to decrease the risks of complication, a precise and meticulous physical examination should be conducted preoperatively. In addition, a surgeon should select appropriate osteotomies to correct complex hallux valgus deformities. As a general principle, the severity of deformity dictates treatment options. PMID- 25129350 TI - Iatrogenic hallux varus treatment algorithm. AB - Iatrogenic hallux varus is a relatively rare complication of corrective hallux valgus surgery that has multiple pathologic facets. It requires a comprehensive assessment that focuses on joint flexibility, joint integrity, soft tissue balance, and bony deformity. A step-wise treatment approach is used to address all elements of the deformity. The literature on hallux varus treatments consists mainly of retrospective case series, with several proposed procedures addressing various degrees of deformity. Comparison of these procedures is a challenging endeavor and each case should be considered on an individual basis. PMID- 25129351 TI - Etiology and management of lesser toe metatarsophalangeal joint instability. AB - The terms crossover toe and lesser metatarsophalangeal joint instability both describe a deterioration of the soft tissue structures that give stability to the lesser MTP joints. Initial treatment regimens focused on indirect repair of the instability without addressing the primary pathology. A staging system of the clinical examination and a grading system of the surgical findings are now available to help surgeons classify and treat the plantar plate insufficiency. Improved imaging techniques and direct surgical repair techniques through a dorsal approach have changed the treatment and possibly the results of this difficult condition. PMID- 25129352 TI - Recurrent metatarsalgia. AB - Recurrent metatarsalgia has a multifactorial etiology. The analysis of the cause is critical in planning appropriate treatment. Understanding etiology helps understand the mechanism of prevention, which is the best treatment. Recurrent metatarsalgia is often due to poor technique or poor understanding of the underlying problem. In hallux valgus surgery, recurrent metatarsalgia can be a problem of position of the first metatarsal after an inappropriate or poorly done first metatarsal osteotomy or a problem of gastrocnemius tightness not previously recognized. The best treatment is to restore the normal anatomy but that is not always possible, and surgery on affected rays could be the solution. PMID- 25129353 TI - Problems associated with the excision of the hallux sesamoids. AB - Disorders of the hallux sesamoids can be a source of considerable pain and disability. Inappropriate or inept removal can lead to further disability and pain. Surgical intervention should only follow careful accurate assessment, appropriate investigation, and failure of conservative treatments. PMID- 25129354 TI - The recurrent Morton neuroma: what now? AB - Interdigital neuromas are a common cause of forefoot pain, and approximately 80% of patients require surgical excision for symptom relief. Although 50% to 85% of patients obtain relief after primary excision, symptoms may recur because of an incorrect diagnosis, inadequate resection, or adherence of pressure on a nerve stump neuroma. The symptom relief rate after reoperation is similar to that after primary excision. A plantar longitudinal incision provides optimal exposure, and transposition of the nerve stump into bone or muscle and avoids traction or pressure on the nerve ending that can result in a painful stump neuroma. Preoperative counseling is essential to align patient expectations with potential outcomes. PMID- 25129355 TI - Recurrent tarsal tunnel syndrome. AB - Recurrence of tarsal tunnel syndrome after surgery may be due to inadequate release, lack of understanding or appreciation of the actual anatomy involved, variations in the anatomy of the nerve(s), failure to execute the release properly, bleeding with subsequent scarring, damage to the nerve and branches, persistent hypersensitivity of the nerves, and preexisting intrinsic damage to the nerve. Approaches include more thorough release, use of barrier materials to decrease adherence of the nerve to surrounding tissues to avoid traction neuritis, excisions of neuromas using conduits, and consideration of nerve stimulators and systemic medications to deal with persistent neural pain. PMID- 25129356 TI - The midfoot is really deformed after hindfoot arthrodesis: how to salvage? AB - Concomitant hindfoot and midfoot deformity is common. Hindfoot fusion is associated with prolonged recovery and significant disability. Further surgery is often required to obtain a plantigrade foot. Understanding normal structural and kinematic relationships between the midfoot and hindfoot, as well as recognizing common combined patterns of midfoot and hindfoot deformity, can minimize the unanticipated consequences of hindfoot fusion. Treatment of residual or resultant midfoot deformity requires a thorough analysis of the deformity and familiarity with a variety of operative techniques for correction. PMID- 25129357 TI - Triple arthrodesis: tips and tricks to navigate trouble. AB - Triple arthrodesis is a powerful corrector of hindfoot deformity related to trauma, rheumatoid arthritis, and long-standing peritalar subluxation with posterior tibial tendon dysfunction. To avoid the common postoperative complications related to triple arthrodesis, one must be meticulous in preoperative evaluation as well as surgical technique. Presented are some tips and tricks to avoid the common complications and provide the patient with a plantigrade, stable foot, as well as some salvage options for triple arthrodesis in a malunited position. PMID- 25129358 TI - Nonunion of fifth metatarsal fractures. AB - Metatarsal fractures are those most frequently encountered in the foot. More than half of these are of the 5th metatarsal. The incidence is increasing, along with the activity levels of the general population. Fractures of the 5th metatarsal require careful evaluation and classification to ensure selection of the optimum treatment plan. Distal fractures rarely require fixation, even when displacement is wide. Cases of established nonunion or refracture require fixation. PMID- 25129359 TI - The treatment of calcaneal malunion. AB - The surgical treatment of calcaneal malunion is technically very demanding and requires a careful assessment of the exact cause of the problem. A number of different surgeries are available depending on the precise cause of symptoms. The results are reasonable and justify surgery in an otherwise disabled group of patients. Calcaneal malunion surgery should not be performed by the occasional surgeon, as the price of error is usually amputation. PMID- 25129360 TI - Ongoing pain and deformity after an excision of the accessory navicular. AB - Although a painful accessory navicula and a pes planus often coexist, they are not necessarily causally related, and each condition should be assessed and treated individually. A child or adolescent will notice the rubbing of an accessory navicula against footwear as the foot and boney swelling grows. The cause of persistent local pain such as inadequate bony resection, scar pain, irritation of the tibialis posterior tendon, and so forth should be sought and addressed; management will depend on the specific presentation and previous procedure performed. The cause of the ongoing pain should be investigated. PMID- 25129361 TI - Taking out the tarsal coalition was easy: but now the foot is even flatter. What now? AB - Patients with a preexisting hindfoot deformity, who undergo resection (with or without soft tissue interposition) of a tarsal coalition, may present with recurrent pain and worsening planovalgus deformity. This is due to the secondary effect of soft tissue contractures (lateral ligaments, peroneal tendons, calf muscles) "pulling" the foot into more valgus. Physiotherapy and insoles may help some patients. Depending on the flexibility of the hindfoot and the presence or otherwise of joint degeneration, joint-preserving corrective procedures or corrective joint fusions may be needed. Gastrocnemius, Achilles, and/or peroneal tendon releases may be required, to avoid equinus or further recurrence. PMID- 25129362 TI - Osteomyelitis of the foot and ankle: diagnosis, epidemiology, and treatment. AB - Osteomyelitis of the foot and ankle is a common, potentially devastating condition with diagnostic and treatment challenges. Understanding the epidemiology and pathogenesis of osteomyelitis can raise clinical suspicion and guide testing and treatments. History and physical examination, laboratory studies, vascular studies, histologic and microbiologic analyses, and various imaging modalities contribute to diagnosis and treatment. Treatment including empiric broad-spectrum antibiotics and surgery should take a multidisciplinary approach to optimize patient factors, ensure eradication of the infection, and restore function. Optimization of vascular status, soft tissues, limb biomechanics, and physiologic state of the patient must be considered to accelerate and ensure healing. PMID- 25129363 TI - Managing complications of foot and ankle surgery. Preface. PMID- 25129364 TI - Retrospective comparison of nucleic acid sequence-based amplification, real-time PCR, and galactomannan test for diagnosis of invasive aspergillosis. AB - Invasive aspergillosis is a life-threatening infection in immunocompromised patients, and treating these infections at an early stage is often crucial for a favorable outcome. Early diagnosis, however, remains challenging. We performed a retrospective comparison of three methods: real-time quantitative PCR (qPCR), nucleic acid sequence-based amplification (NASBA), and galactomannan enzyme linked immunosorbent assay (GM-ELISA); these detect circulating Aspergillus DNA, RNA, and galactomannan, respectively. Blood samples from 80 patients at high risk for invasive aspergillosis were tested by each assay. The sensitivity of NASBA, qPCR, and GM-ELISA was 76.47% (95% CI, 58.4-88.6%), 67.65% (95% CI, 49.4-82.0%), and 52.94% (95% CI, 35.4-69.8%), respectively, and the specificity was 80.43% (95% CI, 65.6-90.1%), 89.13% (95% CI, 75.6-95.9%), and 80.43% (95% CI, 65.6 90.1%), respectively. We also evaluated the efficiency of the three tests in various combinations. Perfect specificity (100%; 95% CI, 90.4-100%) and perfect positive predictive value (100%; 95% CI, 77.1-100%) were achieved by combining NASBA and qPCR testing in series. Testing with both NASBA and qPCR in parallel was the most sensitive and had the highest Youden index. Our data support the great potential of NASBA and qPCR, singly or in combination, for diagnosis of invasive aspergillosis in high-risk populations. PMID- 25129365 TI - Towards the targeted management of Chediak-Higashi syndrome. AB - Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive congenital immunodeficiency caused by mutations in CHS1, a gene encoding a putative lysosomal trafficking protein. In the majority of patients, this disorder is typically characterized by infantile-onset hemophagocytic lymphohistiocytosis (HLH), which is lethal unless allogeneic transplantation is performed. A small number of individuals have the attenuated form of the disease and do not benefit from transplant. Improved outcomes of transplantation have been reported when performed before the development of HLH, thus it is important to quickly differentiate patients that present with the childhood form of disease and to prematurely enroll them into a transplantation protocol. In addition, this would also preclude those that exhibit clinical phenotypes of adolescent and adult CHS from this treatment. Patients with an absence of cytotoxic T lymphocyte (CTL) function have a high risk for developing HLH, and could therefore benefit the most from early hematopoietic stem cell transplantation (HSCT). However, although normal CTL cytotoxicity or bi-allelic missense mutations do not exclude the occurrence of HLH in childhood, a more conservative approach is justified. This article summarizes recent advances in the clinical characterization of CHS patients, provides updates on promising new testing methods, and focuses on specific therapeutic approaches. PMID- 25129366 TI - Factors influencing Oncotype DX use in the management of early breast cancer: a single centre experience. AB - BACKGROUND: Oncotype DX recurrence score is a multi-gene assay which quantifies the risk of distant recurrence in patients with hormone receptor-positive (HR+) early breast cancer (EBC) treated with tamoxifen, and predicts the magnitude of clinical benefit of adjuvant chemotherapy. This retrospective study examined factors that were associated with use of Oncotype DX assay at a tertiary care cancer centre in Ottawa, Canada. METHODS: One hundred consecutive patients (pts) diagnosed with HR+, HER2/neu negative EBC (stage I-II), who underwent Oncotype DX testing (Test Group) between 1st April 2010, and 30th June 2011 were included in the study. A second cohort of 100 randomly selected patients with HR+, HER2/neu negative EBC diagnosed from the same time period who did not receive Oncotype DX testing were used as the control group (Control Group). Demographic and clinicopathologic data were obtained from review of charts. Logistic regression was performed to identify variables associated with Oncotype DX usage. FINDINGS: Median age was 58 years (r: 26-77) in Test Group and 63 years (r: 30-81) in Control Group. Sixty-two patients in the Test Group had T1 tumours, compared with 71 in the Control Group. The median 10-year recurrence risks from Adjuvant! Online were 19% and 12% in the Test Group and Control Group, respectively. Factors significantly associated with the utilisation of Oncotype DX assay on multivariate analysis include age 50-64 (p=0.049), tumour size 10.1-20mm (p=0.008) and grade 2 histological grade (p=0.004). INTERPRETATION: Usage of Oncotype DX assay is associated with several clinicopathological factors. These factors reflect the clinical uncertainty of benefit from chemotherapy in these subpopulations of patients and suggest how Oncotype DX assay could complement clinicopathological factors in helping clinicians on treatment selection. PMID- 25129367 TI - Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE). AB - OBJECTIVES: Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinoma patients. MATERIALS AND METHODS: MOTIVATE is an open-label, multicenter, observational trial with Tarceva((r)) (erlotinib) monotherapy. Enrolled patients with advanced (stage IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses of prior chemotherapy were treated with erlotinib at 150mg/day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and best tumor response rate (RR). RESULTS AND CONCLUSION: In total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months, respectively. Three patients (1.2%) had complete response, 51 patients (20.2%) had partial response and 123 patients (48.8%) had SD. Significantly longer median PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status (ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as a second-line therapy. There was no difference in median OS in cohorts stratified to disease stage and smoking status. Female patients had both longer median PFS and OS. Disease control rate was 70.2%. Our results suggest that erlotinib represents a valid treatment option for patients with KRAS WT lung adenocarcinoma and, moreover, that KRAS mutation analysis could help to identify clinically relevant subgroups of NSCLC patients that may benefit from EGFR-TKI therapy. PMID- 25129368 TI - Retrospective evaluation of thromboembolic events in patients with non-small cell lung cancer treated with platinum-based chemotherapy. AB - OBJECTIVES: Thromboembolic events (TE) are common in patients with cancer and are potentially life-threatening. In lung cancer, little is known about thrombosis during chemotherapy treatment. The aim of this study was to describe the incidence of TE in patients with non-small cell lung cancer (NSCLC), occurring during treatment with platinum-based chemotherapy. METHODS: We retrospectively selected patients with NSCLC treated with platinum-based chemotherapy at the VU University Medical Center Amsterdam between 2000 and 2012. Patients who underwent recent surgery were excluded. All TE were included that occurred from start of chemotherapy treatment until 30 days after last administration. RESULTS: Among 784 included patients, 63 (8.0%) patients had 69 TE during treatment. Forty-five venous TE (VTE) and 24 arterial TE (ATE). Six patients had multiple events within treatment period, 3 of which had simultaneous ATE and VTE. In total, 613 patients were treated with cisplatin, 119 patients received carboplatin and 52 patients received both in first- or second-line treatment. In 8% (55/665) of the patients exposed to cisplatin a TE had occurred vs. 5% (8/171) in patients exposed to carboplatin (p=0.42). The majority of TE occurred in the first 2 cycles (70%). History of TE was related to occurrence of TE during chemotherapy (p<0.01). Median PFS was similar in patients with and without TE (6.2 vs. 7.2 months, respectively; p=0.10). Median OS was significantly shorter in patients with TE (9.5 vs. 12.9 months, respectively; p=0.03). CONCLUSION: In our series, both ATE and VTE were a common finding during chemotherapy. TE was a poor prognostic factor. No difference in TE incidence was found between patients treated with cisplatin or carboplatin. PMID- 25129369 TI - Optimal mediastinal staging in non-small cell lung cancer: what is the role of TEMLA and VAMLA? AB - OBJECTIVES: The aim of this review is to present the current role of two techniques of extensive mediastinal dissection, in the staging of lung cancer. MATERIALS AND METHODS: The authors performed a search for original papers published in English language, peer-reviewed journals. RESULTS: According to the published evidence, definitions of VAMLA and TEMLA are given and the main elements of the operative technique are briefly presented. Extensiveness and completeness of mediastinal lymph node dissection using these techniques, their diagnostic yield as well as complications and use of hospital resources are discussed. The role of VAMLA and TEMLA in the contemporary staging of lung cancer is presented in context of other staging techniques and the current clinical practice guidelines. CONCLUSION: On the basis of the evidence currently available, it may be concluded that VAMLA and TEMLA have no contemporarily use in the routine mediastinal staging of lung cancer. This is because of their invasiveness and - at least for TEMLA - high risk of complications and mortality, which renders it unacceptable as a diagnostic procedure, and also due to the development of equally accurate, but far less invasive techniques, i.e. EBUS-NA and EUS-NA. PMID- 25129371 TI - Maximum tumor diameter adjusted to the risk profile predicts biochemical recurrence after radical prostatectomy. AB - Currently, no consensus exists on the best method for tumor quantification in prostate cancer (PCA), and its prognostic value remains controversial. We evaluated how a newly defined maximum tumor diameter (MTD) might contribute to the prediction of biochemical recurrence (BCR) in a consecutive series of PCA patients treated with radical prostatectomy (RP). Patients with PCA who underwent RP without neoadjuvant therapy at a single center were included for analysis. MTD was defined as the largest diameter of all identified tumors in all three dimensions (i.e., length, width, or depth) of the prostate ("Basel technique"). Cox regression models addressed the association of MTD with BCR in three risk groups (low risk-prostate-specific antigen (PSA) < 10 ng/ml, pT2, and Gleason score (GS) <= 6; intermediate risk-PSA >= 10 and <20 ng/ml and/or pT2 and GS = 7; high risk-PSA > 20 ng/ml or pT3 or GS >= 8) and whole cohort. Within a median follow-up of 44 months (interquartile range (IQR) 23-66), 48 patients (9.4 %) in the intermediate-risk and high-risk groups experienced BCR. In multivariate Cox regression analysis, PSA, pathological stage (pT stage), GS, positive surgical margins (PSMs), and MTD > 19.5 mm were independent predictors for BCR (p < 0.05). In subgroup analysis, MTD as a nominal variable (<24.5 and >24.5 mm) was the only independent predictor of BCR in the intermediate-risk group (hazard ratio (HR) 9.933, 95 % confidence interval (CI) 2.070-47.665; p < 0.05). MTD is an independent risk factor of BCR in PC patients after RP. The combination of the MTD with other well-known prognostic factors after RP may improve decision-making concerning follow-up intensity or adjuvant treatment. PMID- 25129372 TI - Caudal extension graft versus columellar strut with plumping graft for acute nasolabial angle correction in rhinoplasty surgery. AB - Nasal tip support is an important factor to be considered in rhinoplasty surgery. There are several techniques for improving tip support. Caudal extension graft (CEG) and columellar strut with plumping graft (CSPG) are two methods in rhinoplasty surgery. The final goal of this experimental study is to find the most effective method for tip correction among patients with tip ptosis. In this study, we compare two different methods which are used for the tip correction among patients who suffer from acute nasolabial angle (NLA) and columellar retraction. We performed a randomized clinical trial to compare correction ratio of NLA and columellar show obtained via CEG and CSPG methods. Standardized photographs were taken before the surgery and 12 months after the surgery to compare results between two groups. The mean post-operation NLA was 112.55 degrees in CEG and 104.17 degrees in CSPG (p value < 0.001). Correction ratio of NLA was 22.26 degrees in CEG and 13.77 degrees in CSPG (p value < 0.001). The difference in the mean and the correction ratio of NLA were statistically significant in two groups. The mean post-operation columellar show was 3.75 mm in CEG and 3.44 mm in CSPG (p value < 0.083). The correction ratio of columellar show was 1.76 mm in CEG and 1.20 mm in CSPG (p value < 0.007). The difference in the correction ratio of the two groups was statistically significant. Our study reveals that both techniques properly improve NLA and columellar show, however, CEG is a more stable method in patients with tip ptosis. PMID- 25129370 TI - A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells. AB - The transcription factor ThPOK promotes CD4(+) T cell differentiation in the thymus. Here, using a mouse strain that allows post-thymic gene deletion, we show that ThPOK maintains CD4(+) T lineage integrity and couples effector differentiation to environmental cues after antigenic stimulation. ThPOK preserved the integrity and amplitude of effector responses and was required for proper differentiation of types 1 and 2 helper T cells in vivo by restraining the expression and function of Runx3, a nuclear factor crucial for cytotoxic T cell differentiation. The transcription factor LRF acts redundantly with ThPOK to prevent the transdifferentiation of mature CD4(+) T cells into CD8(+) T cells. As such, the ThPOK-LRF transcriptional module was essential for CD4(+) T cell integrity and responses. PMID- 25129373 TI - Reply to the comment to the article "Open partial horizontal laryngectomies: a proposal for classification by the working committee on nomenclature of the European Laryngological Society". PMID- 25129374 TI - Increased frequency of mitral valve prolapse in patients with deviated nasal septum. AB - Any abnormality of collagen may affect the tissues with higher collagen content, e.g., joints, heart valves, and great arteries. Mitral valve prolapse (MVP) is a characteristic of generalized collagen abnormality. Nasal septum (NS) is constituted by osseous and cartilaginous septums that are highly rich in collagen. We evaluated the co-existence of deviation of NS (DNS) in patients with MVP. We retrospectively evaluated the recordings of echocardiographic and nasal examinations of subjects with MVP and DNS. We analyzed the features of MVP and anatomical classification of DNS among subjects. Totally, 74 patients with DNS and 38 subjects with normal nasal passage were enrolled to the study. Presence of MVP was significantly higher in patients with DNS compared to normal subjects (63 vs 26%, p < 0.001). Prolapse of anterior, posterior and both leaflets was higher in patients with DNS. Thickness of anterior mitral leaflet was significantly increased in patients with DNS (3.57 +/- 0.68 vs 4.59 +/- 1.1 mm, p < 0.001) compared to normal subjects. Type I, II, and III, IV DNS were higher in frequency in patients with MVP while type V and VI were higher in normal subjects. DNS is highly co-existent with MVP and increased thickness of mitral anterior leaflet. Generalized abnormality of collagen which is the main component of mitral valves and nasal septum may be accounted for co-existence of MVP and DNS. Also co existence of them may exaggerate the symptoms of patients with MVP due to limited airflow through the nasal passage. PMID- 25129375 TI - Inhibitory effect of naringin on microcystin-LR uptake in the freshwater snail Sinotaia histrica. AB - Gastropods are an important food source for aquatic animals, and have been demonstrated to transfer microcystin (MC) to higher trophic levels through the food web. In this study, we performed an oral administration experiment to evaluate whether naringin can inhibit MC-LR uptake in the freshwater snail Sinotaia histrica. We also observed the effect of MC-LR on the organizational pathology of the hepatopancreas in S. histrica. Following exposure to cells of Microcystis ichthyoblabe, S. histrica showed vacuolization and separation of the basal lamina from cells in the hepatopancreas. Initial treatment with 1mM naringin resulted in the prevention of MC-LR uptake rate by approximately 60% over 8days, whereas initial treatment with 10mM naringin suppressed microcystin uptake in 2days, despite an increase in MC-LR levels in the snail from days 5 to 8. With continuous treatment of 10mM naringin, the uptake prevention rate was 100%. Overall, we observed a strong inhibitory effect against MC-LR with naringin treatment. This study provides a potential mechanism to prevent the uptake of microcystin in the aquatic food web, thereby limiting its toxicity in cyanobacterial bloom-polluted areas where the environment can be controlled and may have further applications in the aquaculture of gastropods. PMID- 25129376 TI - Trophectoderm DNA fingerprinting by quantitative real-time PCR successfully distinguishes sibling human embryos. AB - PURPOSE: To validate a novel and more practical system for trophectoderm DNA fingerprinting which reliably distinguishes sibling embryos from each other. METHODS: In this prospective and blinded study two-cell and 5-cell samples from commercially available sibling cell lines and excess DNA from trophectoderm biopsies of sibling human blastocysts were evaluated for accurate assignment of relationship using qPCR-based allelic discrimination from 40 single nucleotide polymorphisms (SNPs) with low allele frequency variation and high heterozygosity. RESULTS: Cell samples with self relationships averaged 95.1 +/- 5.9 % similarity. Sibling relationships averaged 57.2 +/- 5.9 % similarity for all 40 SNPs, and 40.8 +/- 8.2 % similarity for the 25 informative SNPs. Assignment of relationships was accomplished with 100 % accuracy for cell lines and embryos. CONCLUSIONS: These data demonstrate the first trophectoderm qPCR-based DNA fingerprinting technology capable of unequivocal discrimination of sibling human embryos. This methodology will empower research and development of new markers of, and interventions that influence embryonic reproductive potential. PMID- 25129378 TI - Lead isotope ratios for bullets, a descriptive approach for investigative purposes and a new method for sampling of bullet lead. AB - To establish a link between a bullet fired from a suspected firearm, investigation of striation marks are one of the corner stones in the forensic laboratory. Nevertheless, on some occasions, the bullet may be deformed to such extent that traditional investigation of striation marks will be impossible. Fragments of lead can be investigated by lead isotope ratio determination in order to distinguish between bullets with different origin. This approach initially seems reasonable, since the abundance of lead isotopes varies significantly in nature. To make a method valid for forensic purposes, it is important to have a fundamental understanding of the variation within a box of lead bullets and the expected variation between boxes. Studies of variability within and between boxes of ammunition are imperative to perform any type of forensic interpretation, both in an investigative and evaluative context. This work presents an extensive study of variability within and between boxes of ammunition by use of multicollector inductive coupled mass spectrometry. As a first approximation to classify bullets to any given source, a simple and robust graphical method is presented. In addition, an easy-to-use sampling procedure of lead is presented. PMID- 25129379 TI - Ontological reconstruction of the clinical terminology of traditional Chinese medicine. AB - This study proposes the ontological reconstruction of the current clinical terminology of traditional Chinese medicine (TCM). It also provides an overview of preliminary work related to the said reconstruction, including the ontology based analysis of TCM clinical terminology. We conclude that the ontological reconstruction of TCM clinical terminology provides a proper translation from the idealized organizational model to real-world implementation and to a formalized, shared, and knowledge-based framework. PMID- 25129377 TI - Pharmacologic overview of systemic chlorogenic acid therapy on experimental wound healing. AB - Chlorogenic acid (CGA) is a well-known natural antioxidant in human diet. To understand the effects of CGA on wound healing by enhancing antioxidant defense in the body, the present study sought to investigate the potential role of systemic CGA therapy on wound healing and oxidative stress markers of the skin. We also aimed to understand whether chronic CGA treatment has side effects on pivotal organs or rat bone marrow during therapy. Full-thickness experimental wounds were created on the backs of rats. CGA (25, 50, 100, 200 mg/kg) or vehicle was administered intraperitoneally for 15 days. All rats were sacrificed on the 16th day. Biochemical, histopathological, and immunohistochemical examinations were performed. Possible side effects were also investigated. The results suggested that CGA accelerated wound healing in a dose-dependent manner. CGA enhanced hydroxyproline content, decreased malondialdehyde and nitric oxide levels. and elevated reduced glutathione, superoxide dismutase, and catalase levels in wound tissues. Epithelialization, angiogenesis, fibroblast proliferation, and collagen formation increased by CGA while polymorph nuclear leukocytes infiltration decreased. CGA modulated matrix metalloproteinase-9 and tissue inhibitor-2 expression in biopsies. Otherwise, high dose of CGA increased lipid peroxidation of liver and kidney without affecting the heart and muscle samples. Chronic CGA increased micronuclei formation and induced cytotoxicity in the bone marrow. In conclusion, systemic CGA has beneficial effects in improving wound repair. Antioxidant, free radical scavenger, angiogenesis, and anti inflammatory effects of CGA may ameliorate wound healing. High dose of CGA may induce side effects. In light of these observations, CGA supplementation or dietary CGA may have benefit on wound healing. PMID- 25129380 TI - Clinical data quality problems and countermeasure for real world study. AB - Real world study (RWS) has become a hotspot for clinical research. Data quality plays a vital role in research achievement and other clinical research fields. In this paper, the common quality problems in the RWS of traditional Chinese medicine are discussed, and a countermeasure is proposed. PMID- 25129382 TI - Quantifying the sensitivity of ephemeral streams to land disturbance activities in arid ecosystems at the watershed scale. AB - Large areas of public lands administered by the Bureau of Land Management and located in arid regions of the southwestern United States are being considered for the development of utility-scale solar energy facilities. Land-disturbing activities in these desert, alluvium-filled valleys have the potential to adversely affect the hydrologic and ecologic functions of ephemeral streams. Regulation and management of ephemeral streams typically falls under a spectrum of federal, state, and local programs, but scientifically based guidelines for protecting ephemeral streams with respect to land-development activities are largely nonexistent. This study developed an assessment approach for quantifying the sensitivity to land disturbance of ephemeral stream reaches located in proposed solar energy zones (SEZs). The ephemeral stream assessment approach used publicly-available geospatial data on hydrology, topography, surficial geology, and soil characteristics, as well as high-resolution aerial imagery. These datasets were used to inform a professional judgment-based score index of potential land disturbance impacts on selected critical functions of ephemeral streams, including flow and sediment conveyance, ecological habitat value, and groundwater recharge. The total sensitivity scores (sum of scores for the critical stream functions of flow and sediment conveyance, ecological habitats, and groundwater recharge) were used to identify highly sensitive stream reaches to inform decisions on developable areas in SEZs. Total sensitivity scores typically reflected the scores of the individual stream functions; some exceptions pertain to groundwater recharge and ecological habitats. The primary limitations of this assessment approach were the lack of high-resolution identification of ephemeral stream channels in the existing National Hydrography Dataset, and the lack of mechanistic processes describing potential impacts on ephemeral stream functions at the watershed scale. The primary strength of this assessment approach is that it allows watershed-scale planning for low-impact development in arid ecosystems; the qualitative scoring of potential impacts can also be adjusted to accommodate new geospatial data, and to allow for expert and stakeholder input into decisions regarding the identification and potential avoidance of highly sensitive stream reaches. PMID- 25129381 TI - Dioxin-induced thrombocyte aggregation in zebrafish. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a canonical member of a group of dioxins which are byproducts of industrial combustion and are dangerous environmental pollutants. TCDD has been shown to cause several abnormalities in humans and wildlife, and recently, some dioxins have been found to activate platelets. However, TCDD-mediated platelet activation pathways are elusive and virtually nothing is known about TCDD activation of fish thrombocytes. To investigate TCDD effect on thrombocyte function, we tested zebrafish blood in presence of TCDD using a thrombocyte functional assay. We found that TCDD activated thrombocytes. Further experiments showed that thrombocytes of fish treated with TCDD formed both aggregates and filopodia. To investigate the mechanism of TCDD-mediated activation of thrombocytes we used inhibitors for Gq, cyclooxygenase-1, aryl hydrocarbon receptor (AHR), c-src, Akt, and ERK1/2. We found that TCDD induces AHR which activates c-src and signals the activation of Akt and ERK1/2 which are ultimately involved in generation of thromboxane A2. Furthermore, we found that ADP potentiates TCDD action, which led to the discovery that ADP itself activates AHR in the absence of TCDD. Taken together, these results resolved the pathway of TCDD activation of thrombocytes and led to the finding that ADP is an activator of AHR. PMID- 25129383 TI - Nickel(II) biosorption from aqueous solutions by shrimp head biomass. AB - The present study evaluates the capacity of shrimp (Farfantepenaeus aztecus) head to remove toxic Ni(II) ions from aqueous solutions. Relevant parameters that could affect the biosorption process, such as shrimp head pretreatment, solution pH level, contact time and initial Ni(II) concentration, were studied in batch systems. An increase in Ni(II) biosorption capacity and a reduction in the time required to reach Ni(II) biosorption equilibrium was manifested by shrimp head biomass pretreated by boiling in 0.5 N NaOH for 15 min; this biomass was thereafter denominated APSH. The optimum biosorption level of Ni(II) ions onto APSH was observed at pH 7.0. Biosorption increased significantly with rising initial Ni(II) concentration. In terms of biosorption dynamics, the pseudo-second order kinetic model described Ni(II) biosorption onto APSH best. The equilibrium data adequately fitted the Langmuir isotherm model within the studied Ni(II) ion concentration range. According to this isotherm model, the maximum Ni(II) biosorption capacity of APSH was 104.22 mg/g. Results indicate that APSH could be used as a low-cost, environmentally friendly, and promising biosorbent with high biosorption capacity to remove Ni(II) from aqueous solutions. PMID- 25129384 TI - Detection of a pneumonia virus of mice (PVM) in an African hedgehog (Atelerix arbiventris) with suspected wobbly hedgehog syndrome (WHS). AB - A pneumonia virus of mice (PVM) from an African hedgehog (Atelerix arbiventris) with suspected wobbly hedgehog syndrome (WHS) was detected and genetically characterized. The affected hedgehog had a nonsuppurative encephalitis with vacuolization of the white matter, and the brain samples yielded RNA reads highly homogeneous to PVM strain 15 (96.5% of full genomic sequence homology by analysis of next generation sequencing). PVM antigen was also detected in the brain and the lungs immunohistochemically. A PVM was strongly suggested as a causative agent of encephalitis of a hedgehog with suspected WHS. This is a first report of PVM infection in hedgehogs. PMID- 25129385 TI - Minimally invasive surgery with spotlight work channel system in the treatment of lumbar disc herniation: a retrospective study of 21 cases. AB - A group of lumbar discherniation cases was treated with posterior discectomy and decompression with Spotlight working channel. We retrospectively studied these patients. To study and analyze the clinical efficacy and technical features of discectomy which is carried out with the Spotlight channel technology. The development of the minimally invasive spine surgery technology promotes new instruments and materials. For minimally invasive spine surgery in channel technology, the newly launched Depuy(Spine) working channel-Spotlight, which is a new generation of wide viewing angle, single-hole device for minimally invasive spine operations, has good prospects for clinical application. From March 2011 to March 2012, 21 patients who were diagnosed with lumbar disc herniation were treated with posterior discectomy and decompression with Spotlight working channel, then the lumbar and leg pain visual analogue scale (VAS) scores of before and after surgery and that of the follow-ups and the Oswestry Disability Index were analyzed. All patients were successfully operated, and also they received follow-ups for more than 1 year. The postoperative lumbar and leg pain VAS scores improved significantly compared with the preoperative ones (P < 0.05) and can effectively maintain (P > 0.05). The three time points of lumbar pain VAS were 7.80 +/- 0.49, 1.51 +/- 0.52 and 1.47 +/- 0.59. The leg pain VAS were 7.53 +/- 0.50, 1.58 +/- 0.58 and 1.49 +/- 0.67. During the follow-ups of the cases in this group, no case of disc herniation relapsed. Patients were satisfied with that. The Spotlight channel system is one of the surgical approaches to "minimally invasive spine technology with direct vision". It has a good range of surgical indications. It can be carried out flexibly and used widely, which means it will be easier for the surgeons to master. PMID- 25129386 TI - A review of cavernous malformations with trigeminal neuralgia. AB - Cavernous malformation with trigeminal neuralgia is relatively rare; only 10 cases have been reported. In deciding treatment strategies, it is helpful to classify cavernous malformation according to its origin, as follows: in the Gasserian ganglion (Type G); between the cisternal and intra-axial portions of the trigeminal nerve root (Type C); in the intra-axial trigeminal nerve root in the pons (Type P); or in the spinal tract of the trigeminal nerve root (Type S). A 62-year-old male presented with left trigeminal neuralgia (V2 area) and left facial hypoesthesia. Imaging studies revealed a cerebellopontine angle mass lesion with characteristics of a cavernous malformation and evidence of hemorrhage. The lesion was completely removed via a left anterior transpetrosal approach. The mass was attached to the trigeminal nerve root; it was located between the cisternal and intra-axial portions of the nerve root, and feeding off microvessels from the trigeminal nerve vascular plexus. Histological examination confirmed a cavernous malformation. In this case, the cavernous malformation was Type C. We review cases of cavernous malformation with trigeminal neuralgia and discuss therapeutic strategies according to the area of origin. PMID- 25129387 TI - The islands are different: human perceptions of game species in Hawaii. AB - Hawaii's game animals are all non-native species, which provokes human-wildlife conflict among stakeholders. The management of human-wildlife conflict in Hawaii is further complicated by the discrete nature of island communities. Our goal was to understand the desires and perceived values or impacts of game held by residents of Hawaii regarding six game species [pigs (Sus scrofa), goats (Capra hircus), mouflon (Ovis musimon), axis deer (Axis axis), turkeys (Melagris gallopavo), and doves (Geopelia striata)]. We measured the desired abundance of game on the six main Hawaiian Islands using the potential for conflict index and identified explanatory variables for those desires via recursive partitioning. In 2011 we surveyed 5,407 residents (2,360 random residents and 3,047 pre-identified stakeholders). Overall 54.5 and 27.6 % of the emailed and mailed surveys were returned (n = 1,510). A non-respondent survey revealed that respondents and non respondents had similar interest in wildlife, and a similar education level. The desired abundance of game differed significantly among stakeholders, species, and islands. The desired abundance scores were higher for axis deer, mouflon, and turkeys compared to pigs, goats or doves. Enjoyment at seeing game and the cultural value of game were widespread explanatory variables for desired abundance. Models for Lanai emphasized the economic value of game, whereas models for Maui identified the potential for game to contaminate soil and water. Models for Oahu and Kauai revealed concern for human health and safety. Given our findings we recommend managers design separate management plans for each island taking into consideration the values of residents. PMID- 25129388 TI - A novel surface-confined glucaminium-based ionic liquid stationary phase for hydrophilic interaction/anion-exchange mixed-mode chromatography. AB - Glucaminium-based ionic liquids are a new class of recently developed ionic liquids and prepared by functionalizing the amine group of N-methyl-d-glucamine, which renders them good hydrophilicity due to the presence of the glucose structure and charged quaternary ammonium group. In the present study, a glucaminium-based ionic liquid N,N-diallyl-N-methyl-d-glucaminium bromide was synthesized and subsequently bonded to the surface of 3-mercaptopropyl modified silica materials through "thiol-ene" click chemistry. The obtained stationary phase was characterized by elemental analysis and infrared spectroscopy, and then packed as a HPLC column. A mixture of five nucleosides was used to characterize the separation performance of the obtained column under HILIC mode and the column efficiency was determined with cytidine as the test solute, reaching 80,000plates/m. Then, the retention behavior was evaluated by investigating the effect of various chromatographic factors on retention of different types of solutes, and the results revealed that the developed surface-confined glucaminium based ionic liquid stationary phase exhibited a hydrophilic interaction/anion exchange mixed-mode retention mechanism. Finally, two mixtures of nucleotides and flavonoids were separated on the glucaminium-based ionic liquid column, respectively under hydrophilic interaction and hydrophilic interaction/anion exchange mixed-mode chromatography. In conclusion, the multimodal retention capabilities of the glucaminium-based ionic liquid column could offer a wider range of retention behavior and flexible selectivity toward polar and hydrophilic compounds. PMID- 25129389 TI - Trace analysis of endocrine disrupting compounds in environmental water samples by use of solid-phase extraction and gas chromatography with mass spectrometry detection. AB - A novel analytical method using a continuous solid-phase extraction system in combination with gas chromatography-mass spectrometry for the simultaneous separation and determination of endocrine disrupting compounds (EDCs) is reported. The method was applied to major EDCs of various types including parabens, alkylphenols, phenylphenols, bisphenol A and triclosan in water. Samples were preconcentrated by using an automatic solid-phase extraction module containing a sorbent column, and retained analytes eluted with acetonitrile for derivatization with a mixture of N,O-bis(trimethylsilyl)trifluoroacetamide and trimethylchlorosilane. A number of variables potentially influencing recovery of the target compounds such as the type of SPE sorbent (Silica gel, Florisil, RP C18, Amberlite XAD-2 and XAD-4, Oasis HLB and LiChrolut EN), eluent and properties of the water including pH and ionic strength, were examined. LiChrolut EN was found to be the most efficient sorbent for retaining the analytes, with ~100% efficiency. The ensuing method was validated with good analytical results including low limits of detection (0.01-0.08ng/L for 100mL of sample) and good linearity (r(2)>0.997) throughout the studied concentration ranges. The method exhibited good accuracy (recoveries of 90-101%) and precision (relative standard deviations less than 7%) in the determination of EDCs in drinking, river, pond, well, swimming pool and waste water. Waste water samples were found to contain the largest number and highest concentrations of analytes (3.2-390ng/L). PMID- 25129390 TI - High performance characterization of triacylglycerols in milk and milk-related samples by liquid chromatography and mass spectrometry. AB - In this work, ultra high performance liquid chromatography was used for the characterization of non polar lipids (triacylglycerols) in milk samples of different origin, as well as milk-derivatives. For tackling such a task, three core-shell type octadecylsilica columns were serially coupled, reaching a total stationary phase length of 45cm, using acetonitrile-isopropanol gradient elution allowing triacylglicerol separation according to increasing partition number. The employment of an ion-trap-time-of-flight detection in conjunction with atmospheric-pressure chemical ionization mass spectrometry was carried out to positively identify a number of 243 different triacylglycerols containing up to 22 fatty acids, with 2-22 carbon atom alkyl chain length, and 0-3 double bonds. This work reports an extensive characterization of the triacylglycerol fraction in milk and milk-related samples of different sources. PMID- 25129391 TI - Evaluation of stationary phases packed with superficially porous particles for the analysis of pharmaceutical compounds using supercritical fluid chromatography. AB - Superficially porous particles (SPP), or core shell particles, which consist of a non-porous silica core surrounded by a thin shell of porous silica, have gained popularity as a solid support for chromatography over the last decade. In the present study, five unbonded silica, one diol, and two ethylpyridine (2-ethyl and 4-ethyl) SPP columns were evaluated under SFC conditions using two mixtures, one with 17 drug-like compounds and the other one with 7 drug-like basic compounds. Three of the SPP phases, SunShellTM 2-ethylpyridine (2-EP), PoroshellTM HILIC, and Ascentis((r)) Express HILIC, exhibited superior performances relative to the others (reduced theoretical plate height (hmin) values of 1.9-2.5 for neutral compounds). When accounting for both achievable plate count and permeability of the support using kinetic plot evaluation, the CortecsTM HILIC 1.6MUm and Ascentis((r)) Express HILIC 2.7MUm phases were found to be the best choices among tested SPPs to reach efficiencies up to 30,000 plates in the minimum amount of time. For desired efficiencies ranging from 30,000 to 60,000 plates, the SunShellTM 2-EP 2.6MUm column clearly outperformed all other SPPs. With the addition of a mobile phase additive such as 10mM ammonium formate, which was required to elute the basic components with sharp peaks, the PoroshellTM HILIC, SunShellTM Diol and SunShellTM 2-EP phases represent the most orthogonal SPP columns with the highest peak capacities. This study demonstrates the obvious benefits of using columns packed with SPP on current SFC instrumentation. PMID- 25129392 TI - Identification of coding exon 3 duplication in the BMPR1A gene in a patient with juvenile polyposis syndrome. AB - Juvenile polyposis syndrome is an autosomal dominant inherited disorder characterized by multiple juvenile polyps arising in the gastrointestinal tract and an increased risk of gastrointestinal cancers, specifically colon cancer. BMPR1A and SMAD4 germline mutations have been found in patients with juvenile polyposis syndrome. We identified a BMPR1A mutation, which involves a duplication of coding exon 3 (c.230+452_333+441dup1995), on multiple ligation dependent probe amplification in a patient with juvenile polyposis syndrome. The mutation causes a frameshift, producing a truncated protein (p.D112NfsX2). Therefore, the mutation is believed to be pathogenic. We also identified a duplication breakpoint in which Alu sequences are located. These results suggest that the duplication event resulted from recombination between Alu sequences. To our knowledge, partial duplication in the BMPR1A gene has not been reported previously. This is the first case report to document coding exon 3 duplication in the BMPR1A gene in a patient with juvenile polyposis syndrome. PMID- 25129393 TI - Impact of implantable transvenous device lead location on severity of tricuspid regurgitation. AB - BACKGROUND: Implantable device leads can cause tricuspid regurgitation (TR) when they interfere with leaflet motion. The aim of this study was to determine whether lead-leaflet interference is associated with TR severity, independent of other causative factors of functional TR. METHODS: A total of 100 patients who underwent transthoracic two-dimensional and three-dimensional (3D) echocardiography of the tricuspid valve before and after lead placement were studied. Lead position was classified on 3D echocardiography as leaflet interfering or noninterfering. TR severity was estimated by vena contracta (VC) width. Logistic regression analysis was used to identify factors associated with postdevice TR, including predevice VC width, right ventricular end-diastolic and end-systolic areas, fractional area change, right atrial size, tricuspid annular diameter, TR gradient, device lead age, and presence or absence of lead interference. Odds ratios were used to describe the association with moderate (VC width >= 0.5 cm) or severe (VC width >= 0.7 cm) TR, separately, using bivariate and stepwise multivariate logistic regression analysis. RESULTS: Forty-five of 100 patients showed device lead tricuspid valve leaflet interference. The septal leaflet was the most commonly affected (23 patients). On bivariate analysis, preimplantation VC width, right atrial size, tricuspid annular diameter, and lead leaflet interference were significantly associated with postdevice TR. On multivariate analysis, preimplantation VC width and the presence of an interfering lead were independently associated with postdevice TR. Furthermore, the presence of an interfering lead was the only factor associated with TR worsening, increasing the likelihood of developing moderate or severe TR by 15- and 11-fold, respectively. CONCLUSION: Lead-leaflet interference as seen on 3D echocardiography is associated with TR after device lead placement, suggesting that 3D echocardiography should be used to assess for lead interference in patients with significant TR. PMID- 25129394 TI - Assessment of left ventricular volumes with echocardiography and cardiac magnetic resonance imaging: real-life evaluation of standard versus new semiautomatic methods. AB - BACKGROUND: Routine quantitative assessment of left ventricular (LV) volumes with echocardiography is hindered by time-consuming methods requiring a manual trace of the LV cavity from two apical two-dimensional planes. Thus, the aim of this study was to evaluate faster new semiautomatic echocardiographic methods that could represent a feasible alternative for the assessment of LV volumes and ejection fraction (EF) in clinical practice. METHODS: Two semiautomatic methods, the automated EF (Auto-EF) for two-dimensional echocardiography and the 4D Auto LVQ tool for three-dimensional echocardiography (3DE), were compared with the biplane modified Simpson's method and cardiac magnetic resonance (CMR) imaging in 47 patients. To evaluate the accuracy of volumetry, additional in vitro measurements using water-filled latex balloons were performed with both modalities. RESULTS: Results of balloon volumetry by echocardiography and CMR measurements were in good agreement with real balloon volumes. The mean LV EF was 45 +/- 11% by Auto-EF, 45 +/- 11% by 3DE, 48 +/- 11% by Simpson's method, and 54 +/- 12% by CMR. Linear regression and Bland-Altman analyses showed good associations for semiautomatic methods with Simpson's method (Auto-EF, r = 0.85, bias = 3%, limits of agreement [LOA] = 12%; 3DE, r = 0.79, bias = 3%, LOA = 14%), as well as with CMR (Auto-EF, r = 0.74, bias = 9%, LOA = 17%; 3DE, r = 0.73, bias = 9%, LOA = 17%). Intra- and interobserver variability were 6% and 12% with Auto EF and 8% and 11% with 3DE, respectively. CONCLUSIONS: Good correlations between semiautomatic echocardiographic parameters for assessment of LV volumes and EF could be observed when compared with Simpson's method or CMR. However, intertechnique agreement analysis of absolute LV volumes revealed considerable differences, with significant underestimation of volumes and EF with respect to CMR. PMID- 25129395 TI - A randomized, blinded, controlled USA field study to assess the use of fluralaner tablets in controlling canine flea infestations. AB - BACKGROUND: The novel isoxazoline molecule fluralaner provides 12 weeks activity against fleas and 8 to 12 weeks against tick infestations according to label claims. METHODS: This blinded, multi-center study in client-owned dogs evaluated the flea control provided by a single oral fluralaner treatment (25-56 mg/kg; BravectoTM, Merck Animal Health) compared to a control group administered three oral spinosad (30 - 60 mg/kg; Comfortis(r), Elanco) treatments at 4-week intervals together with an amitraz collar (9%, Preventic(r), Virbac). Households were randomized (3:1 ratio) to either fluralaner (224 dogs, 118 households) or control (70 dogs, 39 households). Within households, one primary dog with at least 10 live fleas at enrollment was randomly selected for whole body flea counts every 4 weeks through Week 12; all dogs were followed for safety until Week 12. Fluralaner dogs received two additional doses at Weeks 12 and 24 for further safety and palatability observations through Week 26. RESULTS: Geometric mean flea count reductions from baseline for the fluralaner group at Weeks 4, 8, and 12 were 99.7%, 99.8%, and 99.8%, respectively; and 96.1%, 99.5%, and 99.6% for the spinosad controls. Percentages of flea-free primary dogs at Weeks 4, 8, and 12 were 91.1%, 95.4%, and 95.3% for the fluralaner group; and 44.7%, 88.2%, and 84.4% for the controls; the differences were significant at Weeks 4 (P < 0.0001) and 12 (P = 0.0370). Improvements in veterinarian assessed flea allergy dermatitis (FAD) were observed in both groups. Fluralaner tablets were accepted free choice in over 90% of doses. The most common adverse event was vomiting, occurring in 7.1% of the fluralaner group and 14.3% of the controls. No treatment related serious adverse events were reported. CONCLUSIONS: A single treatment of dogs with the palatable fluralaner flavored chewable tablet provides a safe and effective option for 12 weeks of flea control at least equivalent to that of 3 sequential treatments with spinosad tablets. Linked to the high level of flea control was a substantial alleviation of associated signs of FAD. PMID- 25129396 TI - Factors associated with gastrostomy tube dependence after concurrent chemoradiotherapy for hypopharyngeal cancer. AB - PURPOSE: We aimed to identify tumor- and treatment-related factors predicting gastrostomy tube dependence after concurrent chemoradiotherapy (CCRT) for hypopharyngeal cancer. METHODS: We performed a retrospective review of all patients with hypopharyngeal cancer treated with CCRT between 2002 and 2012 except for those with residual or recurrent disease at evaluation. The incidence of gastrostomy tube dependence, defined as complete or almost complete dependence on tube feeding, at 6 months after the completion of treatment was the endpoint. A total of 75 patients were analyzed in this study. RESULTS: Twelve patients (16 %) showed gastrostomy tube dependence. Among tumor-related factors, the subsite (posterior wall versus pyriform sinus plus postcricoid) was the most significant factor correlated with gastrostomy tube dependence (p < 0.01 by multivariate analysis). The T category of the primary tumor was also correlated with gastrostomy tube dependence on univariate analysis (p < 0.01). Among treatment related factors, the radiation dose was not associated with gastrostomy tube dependence. On the other hand, gastrostomy tube dependence was also correlated with the requirement of supportive nutrition with a nasogastric tube at the beginning of and during treatment (both p < 0.01). CONCLUSION: Risk factors for gastrostomy tube dependence after the completion of CCRT for hypopharyngeal cancer were identified. PMID- 25129397 TI - Exploring the views of parents regarding dietary habits of their young cancer surviving children. AB - PURPOSE: Adult survivors of childhood cancer have a poor dietary intake. These habits may be manifesting themselves soon after treatment completion. This qualitative study aimed to assess parental views regarding the dietary habits of young child cancer survivors. METHODS: The parents/carers of 18 young child cancer patients (YCCP) treated at Sydney Children's Hospital, Australia (<5 years since treatment completion and <13 years of age), participated in this study. Eighteen age- and sex-matched healthy controls were recruited from Sydney-based community organizations. The interview schedule was semi-structured, and the interview was conducted over the telephone. Interviews were conducted until thematic saturation was reached. Coding and analysis was facilitated by qualitative analysis software. RESULTS: Three main themes emerged regarding parental perceptions of YCCP current intake as compared with their pre-diagnosis eating habits: (1) decreased fruit and vegetable intake, (2) increased consumption of "junk food," and (3) increased portion sizes. Parents also described a continuation of poor eating habits that were established during their cancer treatment. The eating habits of YCCP were substantively different to that described by parents of the control group. CONCLUSION: This exploratory project revealed parental concern regarding their child's dietary intake once the cancer treatment had been completed. The varying habits of YCCP are likely multifactorial and may be related to treatment-related side effects and food habits established during the cancer treatment. PMID- 25129399 TI - Handmade trileaflet valved stent graft for pulmonary valve implantation. PMID- 25129398 TI - Have "new" methods in medical education reached German-speaking Central Europe: a survey. AB - BACKGROUND: Simulation-based-training (SBT) in the education of health professionals is discussed as an effective alternative for knowledge and skills enhancement as well as for the establishment of a secure learning environment, for learners and patients. In the Anglo-American region, SBT and simulation and training centers (STC) are numbered as standard for medical training. In German speaking Central Europe, priority is still given to the establishment of SBT and STC. The purpose of this study was (i) to survey the status quo relating to the existence and facilities of simulation and training centers at medical universities in German-speaking Central Europe and (ii) the evaluation of training methods, especially in the area of emergency medicine skills. METHODS: All public and private medical universities or medical faculties in Germany (36), Austria (4) and German-speaking Switzerland (3) were interviewed. In the survey, information regarding the existence and facilities of STCs and information with regards to the use of SBT in the area of emergency medicine was requested. The questions were partly posed in a closed-ended-, in an open-ended- and in a multiple choice format (with the possibility of selecting more than one answer). RESULTS: Of a total of 43 contacted medical universities/medical faculties, 40 ultimately participated in the survey. As decisive for the establishment of a STC the potential to improve the clinical-practical training and the demand by students were listed. Obligatory training in a STC during the first and sixth academic year was confirmed only by 12 institutions, before the first invasive procedure on patients by 17 institutions. 13 institutions confirmed the use of the STC for the further training of physicians and care-staff. Training for the acute care and emergency medicine skills in the field of pediatrics, for the most part, occurs decentralized. CONCLUSIONS: New methods in medical training have reached German-speaking Central Europe, but the simulation and training centers vary in size, equipment or regarding their integration into the obligatory curriculum as much as the number and variety of the offering to be trained voluntarily or on an obligatory basis. PMID- 25129400 TI - Targeting the parahippocampal area by auditory cortex stimulation in tinnitus. AB - BACKGROUND: The final common pathway in tinnitus generation is considered to be synchronized auditory oscillatory hyperactivity. Intracranial auditory cortex stimulation (iACS) via implanted electrodes has been developed to treat severe cases of intractable tinnitus targeting this final common pathway, in the hope of being a panacea for tinnitus. However, not everybody responds to this treatment. OBJECTIVE: The electrical brain activity and functional connectivity at rest might determine who is going to respond or not to iACS and might shed light on the pathophysiology of auditory phantom sound generation. METHOD: The resting state electrical brain activity of 5 patients who responded and 5 patients who did not respond to auditory cortex implantation are compared using source localized spectral activity (Z-score of log transformed current density) and lagged phase synchronization. RESULTS: sLORETA source localization reveals significant differences between responders vs non-responders for beta3 in left posterior parahippocampal, hippocampal and amygdala area extending into left insula. Gamma band differences exist in the posterior parahippocampal areas and BA10. Functional connectivity between the auditory cortex and the hippocampal area is increased for beta2, delta and theta2 in responders, as well as between the parahippocampal area and auditory cortex for beta3. CONCLUSION: The resting state functional connectivity and activity between the auditory cortex and parahippocampus might determine whether a tinnitus patient will respond to a cortical implant. The auditory cortex may only be a functional entrance into a larger parahippocampal based tinnitus network. PMID- 25129401 TI - The effects of anodal stimulation of the left prefrontal cortex on sentence production. AB - BACKGROUND: Most studies in which Anodal Transcranial Direct Current Stimulation (A-tDCS) has been used to improve language production have focused on single words. Yet sentence production requires more than lexical retrieval. For example, successful suppression of the past and careful planning of the future are two critical requirements for producing a correct sentence. Can A-tDCS improves those, and by extension, production at the sentence level? OBJECTIVE/HYPOTHESIS: Given that many aspects of sentence production beyond word retrieval require frontally-mediated operations, we hypothesized that A-tDCS to the left prefrontal cortex should benefit various operation involved in producing sentences, two of which, suppression of the past and planning of the future, were targeted in this study. METHODS: We used a paradigm that elicited construction of sentences through event description, but was structured enough to allow for between-subject comparison, clear error identification, and implementation of experimental manipulations to probe certain aspects of production. RESULTS: We showed that A tDCS to the left PFC reliably decreased the number of incomplete and errorful sentences. When the origin of this improvement was probed, we found that A-tDCS significantly decreased errors due to premature commitment to the future word (insufficient internal monitoring), and had a marginal effect on errors of perseverations (insufficient suppression of the past). CONCLUSION: We conclude that A-tDCS is a promising tool for improving production at the sentence level, and that improvement can be expected when internal monitoring and control over verbal responses is impaired, or for certain cases of perseveratory errors. PMID- 25129402 TI - Endogenous cortical oscillations constrain neuromodulation by weak electric fields. AB - BACKGROUND: Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation modality that may modulate cognition by enhancing endogenous neocortical oscillations by application of sine-wave electric fields. Yet, the role of endogenous network activity in enabling and shaping the effects of tACS has remained unclear. OBJECTIVE: We combined optogenetic stimulation and multichannel slice electrophysiology to elucidate how the effect of a weak sine wave electric field depends on the ongoing cortical oscillatory activity. We hypothesized that endogenous cortical oscillations constrain neuromodulation by tACS. METHODS: We studied the effect of weak sine-wave electric fields on oscillatory activity in mouse neocortical slices. Optogenetic control of the network activity enabled the generation of in vivo-like cortical oscillations for studying the temporal relationship between network activity and sine-wave electric field stimulation. RESULTS: Weak electric fields enhanced endogenous oscillations but failed to induce a frequency shift of the ongoing oscillation for stimulation frequencies that were not matched to the endogenous oscillation. This constraint on the effect of electric field stimulation imposed by endogenous network dynamics was limited to the case of weak electric fields targeting in vivo-like network dynamics. Together, these results suggest that the key mechanism of tACS may be enhancing, but not overriding, intrinsic network dynamics. CONCLUSION: Our results contribute to understanding the inconsistent tACS results from human studies and propose that stimulation precisely adjusted in frequency to the endogenous oscillations is key to rational design of non invasive brain stimulation paradigms. PMID- 25129403 TI - Elevated levels of Th17 cells and Th17-related cytokines are associated with disease activity in patients with inflammatory bowel disease. AB - OBJECTIVE: Interleukin-17(IL-17)-producing T helper(Th)17 cells are considered as a new subset of cells critical to the development of inflammatory bowel disease (IBD). We aimed to investigate the distribution of Th17 cells, the expressions of Th17-related cytokines (IL-17, IL-21 and IL-22) and their association with disease activity in IBD patients. METHODS: We collected intestinal tissue biopsies from 40 patients with active ulcerative colitis (UC), 20 patients with active Crohn's disease (CD) and 20 healthy controls. The distribution of Th17 cells and expressions of Th17-related cytokines in colonic tissues were evaluated by a standard immunohistochemical procedure. Serum IL-17, IL-21 and IL-22 levels were determined by ELISA. Pearson's and Spearman's correlation analyses were performed to analyze the correlation between the number of Th17 cells, the expressions of Th17-related cytokines and disease activity index, endoscopic and histological grading, and CRP and PLT levels, respectively. RESULTS: Compared with healthy controls, the number of Th17 cells and the expressions of IL-17, IL 21 and IL-22 were significantly increased in active IBD patients (P < 0.05). In addition, Pearson's and Spearman's correlation analyses showed that the number of Th17 cells and the expressions of Th17-related cytokines were correlated with disease activity index, endoscopic and histological grading, CRP and PLT levels (P < 0.05). CONCLUSIONS: Th17 cells and Th17-related cytokines (IL-17, IL-21 and IL-22) were increased in the intestinal mucosa in active IBD patients and may play an important role in disease activity and mucosal damage. PMID- 25129404 TI - A novel method for passing cerebrospinal fluid shunt tubing: a proof of principle study. AB - INTRODUCTION: Few innovations in the method of tunneling shunt tubing for cerebrospinal fluid (CSF) shunt diversion have been made since this treatment of hydrocephalus was first developed. Therefore, this feasibility study was performed with the hope of identifying an improved technique that could potentially carry fewer complications. MATERIALS AND METHODS: On 10 cadaver sides and when placed in the supine position, small skin incisions were made at the clavicle and ipsilateral subcostal region, and magnets were used to pass standard shunt tubing between the two incisions. RESULTS: Nickel-plated magnets were less effective in pulling the shunt tubing below the skin compared with ceramic magnets. Of these, magnets with pull strengths of 150-200 lbs were the most effective in dragging the subcutaneous tubing between the two incisions. No obvious damage to the skin from the overlying magnet was seen in any specimen. CONCLUSIONS: Few options exist for tunneling distal shunt tubing for CSF shunt procedures. Future patient studies are needed to determine if the technique described herein is superior to current methods, particularly when examining patient groups that are at a greater risk for injury during tunneling shunt catheters. PMID- 25129405 TI - A trimodality comparison of volumetric bone imaging technologies. Part I: Short term precision and validity. AB - In vivo peripheral quantitative computed tomography (pQCT) and peripheral magnetic resonance imaging (pMRI) modalities can measure apparent bone microstructure at resolutions 200 MUm or higher. However, validity and in vivo test-retest reproducibility of apparent bone microstructure have yet to be determined on 1.0 T pMRI (196 MUm) and pQCT (200 MUm). This study examined 67 women with a mean age of 74+/-9 yr and body mass index of 27.65+/-5.74 kg/m2, demonstrating validity for trabecular separation from pMRI, cortical thickness, and bone volume fraction from pQCT images compared with high-resolution pQCT (hr pQCT), with slopes close to unity. However, because of partial volume effects, cortical and trabecular thickness of bone derived from pMRI and pQCT images matched hr-pQCT more only when values were small. Short-term reproducibility of bone outcomes was highest for bone volume fraction (BV/TV) and densitometric variables and lowest for trabecular outcomes measuring microstructure. Measurements at the tibia for pQCT images were more precise than at the radius. In part I of this 3-part series focused on trimodality comparisons of precision and validity, it is shown that pQCT images can yield valid and reproducible apparent bone structural outcomes, but because of longer scan time and potential for more motion, the pMRI protocol examined here remains limited in achieving reliable values. PMID- 25129406 TI - A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part II: 1-Yr Change, Long-Term Precision, and Least Significant Change. AB - The previous article in this 3-part series demonstrated short-term precision and validity for volumetric bone outcome quantification using in vivo peripheral (p) quantitative computed tomography (pQCT) and magnetic resonance imaging (MRI) modalities at resolutions 200 MUm or higher. However, 1-yr precision error and clinically significant references are yet to be reported for these modalities. This study examined 59 women with mean age of 75 +/- 9 yr and body mass index of 26.84 +/- 4.77 kg/m2, demonstrating the lowest 1-yr precision error, standard errors of the estimate, and least significant change values for high-resolution (hr) pQCT followed by pQCT, and 1.0-T pMRI for all volumetric bone outcomes except trabecular number. Like short-term precision, 1-yr statistics for trabecular separation were similar across modalities. Excluding individuals with a previous history of fragility fractures, or who were current users of antiresorptives reduced 1-yr change for bone outcomes derived from pQCT and pMR images, but not hr-pQCT images. In Part II of this 3-part series focused on trimodality comparisons of 1-yr changes, hr-pQCT was recommended to be the prime candidate for quantifying change where smaller effect sizes are expected, but pQCT was identified as a feasible alternative for studies expecting larger changes. PMID- 25129408 TI - UPLC-MS/MS determination of thiamphenicol in human plasma and its application to a pharmacokinetic study. AB - A sensitive and rapid ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to determine thiamphenicol (TAP) in human plasma using chlorzoxazone as the internal standard (IS). Sample preparation was accomplished through a liquid-liquid extraction procedure with ethyl acetate to precipitation of plasma protein, and to a 0.1 mL plasma sample. The analyte and IS were separated on an Acquity UPLC BEH C18 column (2.1 mm * 50 mm, 1.7 MUm) with the mobile phase of acetonitrile and 1% formic acid in water with gradient elution at a flow rate of 0.40 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z 354.3->185.1 for TAP and m/z 168.1->132.1 for IS. The linearity of this method was found to be within the concentration range of 10-8000 ng/mL with a lower limit of quantification of 10 ng/mL. Only 1.5 min was needed for an analytical run. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of TAP in healthy Chinese volunteers after oral administration. PMID- 25129407 TI - A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part III: SD, SEE, LSC Association With Fragility Fractures. AB - Part II of this 3-part series demonstrated 1-yr precision, standard error of the estimate, and 1-yr least significant change for volumetric bone outcomes determined using peripheral (p) quantitative computed tomography (QCT) and peripheral magnetic resonance imaging (pMRI) modalities in vivo. However, no clinically relevant outcomes have been linked to these measures of change. This study examined 97 women with mean age of 75 +/- 9 yr and body mass index of 26.84 +/- 4.77 kg/m(2), demonstrating a lack of association between fragility fractures and standard deviation, least significant change and standard error of the estimate-based unit differences in volumetric bone outcomes derived from both pMRI and pQCT. Only cortical volumetric bone mineral density and cortical thickness derived from high-resolution pQCT images were associated with an increased odds for fractures. The same measures obtained by pQCT erred toward significance. Despite the smaller 1-yr and short-term precision error for measures at the tibia vs the radius, the associations with fractures observed at the radius were larger than at the tibia for high-resolution pQCT. Unit differences in cortical thickness and cortical volumetric bone mineral density able to yield a 50% increase in odds for fractures were quantified here and suggested as a reference for future power computations. PMID- 25129409 TI - Simultaneous determination of N(1)-methylnicotinamide, L-carnitine, and creatinine in human plasma and urine by liquid chromatography with mass spectrometry for assessing the activities of multiple renal cationic transporters. AB - Organic cation transporters are responsible for the disposition of various endogenous and therapeutic agents in humans; thus, there is a great need for the development of a simple assay for simultaneous assessment of the activities of multiple transporters. Using liquid chromatography-mass spectrometry (LC/MS), we developed an assay that allows for simultaneous quantitation of plasma and urinary levels of N(1)-methylnicotinamide (a substrate of hOCT2/hMATEs), L carnitine (a substrate of hOCTN2), and creatinine (an indicator of glomerular filtration). Samples were diluted with ultrapure water, deproteinized with trichloroacetic acid, filtered, and then injected on a cation exchange column. The analytes were separated with a gradient LC technique and detected by MS. The total assay time was less than 8 min. The lower detection limits for N(1) methylnicotinamide, L-carnitine, and creatinine were 2, 10, and 24 ng/mL, respectively. Recovery of the analytes was almost complete. A preliminary clinical study conducted in 25 healthy subjects revealed that the mean+/-SD for the renal clearance (CLR) of N(1)-methylnicotinamide (272.7+/-81.0 mL/min) far exceeded the glomerular filtration rate (116.3+/-19.6 mL/min), indicating the involvement of active tubular secretion, while the mean CLR of clearance of L carnitine was close to nil (1.5+/-1.4 mL/min), indicating almost complete tubular reabsorption. The present method is potentially useful for clinical studies on the genetic control of cationic transporter activities and the transporter mediated drug interactions. PMID- 25129410 TI - Simultaneous multi-component quantitation of Chinese herbal injection Yin-zhi huang in rat plasma by using a single-tube extraction procedure for mass spectrometry-based pharmacokinetic measurement. AB - Ying-zhi-huang injection (YZH-I) is an injectable multi-herbal prescription derived from the ancient Chinese remedy "Yin-chen-hao-tang", which is widely used in the clinic for the treatment of jaundice and chronic liver diseases. To date, little information is available on the pharmacokinetic properties of this poly herbal formulation. Herein, we reported a simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitative multiple reaction monitoring (MRM) of eight major ingredients of YZH-I (including baicalin, baicalein, wogonoside, geniposide, geniposidic acid, chlorogenic acid, neochlorogenic acid, and caffeic acid) in rat plasma. A fast single-tube multi impurity precipitation extraction ("SMIPE") procedure was introduced for straightforward plasma preparation, based on one-pot deproteinization precipitation with acidified methanol extraction and in-situ multifunction impurity removal by a solid sorbent mixture (anh. magnesium sulfate plus octadecylsilane). Particularly, the addition of ascorbic acid in methanol (10 mg/mL) was found to exhibit a pronounced protective effect and significantly increase extraction effectiveness of the herbal phenolic components. Some pretreatment variables (protein precipitating solvent, acidifying agent and sorbent) were optimized with acceptable matrix effect (-18 to 7.7%), extraction recovery (65-88%) and process efficiency (62-91%) for the SMIPE-based LC-MRM multi-analyte quantitation using matrix-matched calibration (5-1000 ng/mL) without using internal standard. Mean accuracies were obtained in the range of 83 114% at three different fortification levels, with intra- and inter-day variations within 13%. This validated method was successfully applied to the simultaneous measurement and pharmacokinetic investigation of the chemical constituents in rats following an intravenous administration of YZH-I. PMID- 25129411 TI - Simultaneous determination of seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill by liquid chromatography-electrospray ionization-tandem mass spectrometry: application to a pharmacokinetic study. AB - A liquid chromatography-electrospray ionization-tandem mass spectrometry method was described for the simultaneous determination of resibufogenin, bufalin, gamabufotalin, telibufagin, arenobufagin, cinobufagin and bufotalin in rat plasma. Plasma samples were pretreated by liquid-liquid extraction with ethyl acetate. Chromatographic separation was carried out on an ACQUITY HSS T3 column with gradient elution using mobile phase consisting of acetonitrile-0.1% formic acid in water at a flow rate of 0.3 mL/min. All analytes showed good linearity over a wide concentration range (r>0.99). The lower limit of quantification was in the range of 0.5-10 ng/mL for seven bufadienolides. The mean recovery of the analytes ranged from 94.36 to 104.18%. The intra- and inter-day precisions were in the range of 1.74-13.78% and the accuracies were between 89.37 and 101.38%. The validated method was successfully applied to a pharmacokinetic (PK) study of the seven bufadienolides in rat plasma after oral administration of Shexiang Baoxin Pill (SBP). The selected PK marker compounds with typical efficacy/toxicity may provide a practical solution for marker compound selection and dosage design for the therapeutic drug monitoring and PK study of SBP in its clinical applications. PMID- 25129412 TI - Chromatographic fingerprint analysis of metabolites in natural and artificial agarwood using gas chromatography-mass spectrometry combined with chemometric methods. AB - Agarwood is a resinous material formed in wounded Aquilaria sinensis in China, which is widely used as an effective traditional Chinese medicine (TCM). This study is aimed to use gas chromatography-mass spectrometry combined with chemometric methods to create reliable criteria for accurate identification of natural agarwood and artificial agarwood, as well as for quality evaluation of artificial agarwood. Natural agarwood and artificial agarwood (stimulated by formic acid or formic acid plus fungal inoculation) were used as standards and controls for the gas chromatography-mass spectrometry (GC-MS) and multivariate analysis. The identification criteria developed were applied to commercial agarwood. A reliable criteria including correlation coefficient of GC-MS fingerprint of natural agarwood and 22 markers of metabolism in natural and artificial agarwood was constructed. Compared with chemically stimulated agarwood (formic acid) and in terms of the 22 markers, artificial agarwood obtained by formic acid stimulation and fungal inoculation were much closer to natural agarwood. The study demonstrates that the chemical components of artificial agarwood obtained by comprehensive stimulated method (formic acid plus fungal inoculation) are much closer to the natural agarwood than those obtained by chemically stimulated method (formic acid), as times goes by. A reliable criteria containing correlation coefficient of GC-MS fingerprint of natural agarwood and 22 metabolism markers can be used to evaluate the quality of the agarwood. As an application case, three samples were identified as natural agarwood from the 25 commercial agarwood by using the evaluation method. PMID- 25129413 TI - Enhanced metabolic and redox activity of vascular aquatic plant Lemna valdiviana under polarization in Direct Photosynthetic Plant Fuel Cell. AB - In this study, duckweed species Lemna valdiviana was investigated as a photoautotrophycally grown biocatalyst in recently developed Direct Photosynthetic Plant Fuel Cell. Stable current outputs, reaching maximum of 226+/ 11 mA/m(2), were achieved during the operating period. The electricity production is associated with electrons generated through the light-dependent reactions in the chloroplasts as well as the respiratory processes in the mitochondria and transferred to the anode via endogenous electron shuttle, synthesized by the plants as a specific response to the polarization. In parallel, a considerable increase in the content of proteins (47%) and reserve carbohydrates (44%) of duckweeds grown under polarization conditions was established by means of biochemical analyses. This, combined with the electricity generation, makes the technology a feasible approach for the duckweed farming. PMID- 25129414 TI - Pollution profiles and health risk assessment of VOCs emitted during e-waste dismantling processes associated with different dismantling methods. AB - Pollution profiles of typical volatile organic compounds (VOCs) emitted during dismantling of various printed circuit board assemblies (PCBAs) of e-wastes using different methods were comparatively investigated in the real e-waste dismantling workshops in South China in April 2013. Similar pollution profiles and concentrations of VOCs were observed between dismantling mobile phone and hard disk PCBAs by using electric blowers and between dismantling television and power supplier PCBAs using electric heating furnaces. Aromatic hydrocarbons (accounting for >60% of the sum of VOCs) were the dominant group during using electric blowers, while aromatic (accounting for >44% of the sum of VOCs) and halogenated hydrocarbons (accounting for >48% of the sum of VOCs) were the two dominant groups which contributed equally using electric heating furnaces. However, the distribution profiles of VOCs emitted during dismantling of televisions, hard disks and micro motors using rotary incinerators varied greatly, though aromatic hydrocarbons were still the dominant group. The combustion of e-wastes led to the most severe contamination of VOCs, with total VOCs (3.3*10(4) MUg m(-3)) using rotary incinerators about 190, 180, 139, and 40 times higher than those using mechanical cutting, electric soldering iron, electric blower, and electric heating furnace, respectively. Both cancer and non-cancer risks existed for workers due to exposure to on-site emitted VOCs in all workshops especially in those using rotary incinerators according to the USEPA methodology, whereas only cancer risks existed in rotary incinerator workshops according to the American Conference of Industrial Hygienists methodology. PMID- 25129415 TI - Influence of pharyngolaryngeal anomalies diagnosed through indirect laryngoscopy in the prediction of difficult intubation. AB - OBJECTIVE: To determine the pharyngolaryngeal anomalies not usually included in the evaluation of difficult airway, in order to investigate the influence of these anomalies in the prediction of difficult intubation. To do this, indirect laryngoscopy with a 70 degrees rigid laryngoscope was performed on all patients during the preoperative period. METHODS: This is an observational, prospective study on 300 consecutive patients who were scheduled for endotracheal intubation under general anesthesia. In addition to assessing the airway in the preoperative period by demographic and clinical predictors of difficult airway, rigid indirect laryngoscopy was performed to diagnose pharyngolaryngeal anomalies. Later, under general anesthesia and direct laryngoscopy it was checked to see if there was difficulty in intubating the larynx, and its association with all previous variables was investigated. A logistic regression model for prediction purposes was developed, and its power of discrimination was achieved by assessing the area under the curve. RESULTS: During the examination by indirect laryngoscopy 46 anomalies were found, which were as follows: 31 abnormalities of the epiglottis (22 omega epiglottis, 9 flaccid or hypertrophic epiglottis); 6 findings of hypertrophic lingual tonsils, 3 cases of upper airway tumors, and 6 patients with tongue disorders. Intubation difficulty was found in 14 cases (4.66%). The regression model found, and its coefficients to develop it were: f(x)=1.322+(2.173 thyromental distance <6.5 cm)+(1.813 omega epiglottis) (1.310*cm opening mouth). Global power of discrimination was 0.83, with a 95% confidence interval from 0.709 to 0.952). CONCLUSION: Indirect laryngoscopy allowed pharyngolaryngeal anomalies to be diagnosed, including omega epiglottis, which was one of the variables included in the logistic regression model. PMID- 25129416 TI - Clinical decision rules and D-Dimer in venous thromboembolism: current controversies and future research priorities. AB - Venous thromboembolism (VTE) is a potentially lethal clinical condition that is suspected in patients with common clinical complaints, in many and varied, clinical care settings. Once VTE is diagnosed, optimal therapeutic management (thrombolysis, IVC filters, type and duration of anticoagulants) and ideal therapeutic management settings (outpatient, critical care) are also controversial. Clinical prediction tools, including clinical decision rules and D Dimer, have been developed, and some validated, to assist clinical decision making along the diagnostic and therapeutic management paths for VTE. Despite these developments, practice variation is high and there remain many controversies in the use of the clinical prediction tools. In this narrative review, we highlight challenges and controversies in VTE diagnostic and therapeutic management with a focus on clinical decision rules and D-Dimer. PMID- 25129417 TI - Communication in healthcare: lessons from diversity. PMID- 25129418 TI - Origin of plant auxin biosynthesis. AB - The recent finding of the tryptophan aminotransferase (TAA)/flavin monooxygenase (YUC) pathway as the principal route of auxin production in plants provides an opportunity to revisit the origin of plant auxin biosynthesis. Phylogenetic analyses of the TAA and YUC gene families provide very little evidence for the production of indole-3-acetic acid (IAA) in algae. Instead, horizontal gene transfer of YUCs from bacteria to the ancestral land plant suggests that the TAA/YUC pathway is a land plant innovation. In this Opinion article we postulate that the origin of tryptophan-dependent IAA biosynthesis in land plants might have evolved in response to interactions with microbes, particularly bacteria, allowing plants to counteract bacterial activities and control their own auxin signaling. PMID- 25129419 TI - [Paraneoplastic sensory neuropathy associated with squamous cell carcinoma of the larynx]. PMID- 25129420 TI - Metastatic hepatocellular carcinoma to parotid glands. AB - PATIENT: Male, 66. FINAL DIAGNOSIS: Hepatocellular carcinoma. SYMPTOMS: Abdominal distension * painful right facial swelling * weight loss. MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: -. OBJECTIVE: Rare disease. BACKGROUND: Hepatocellular carcinoma is a common cancer, but it rarely metastasizes to the salivary glands. A review of the literature revealed only 5 reported cases of hepatocellular carcinoma metastatic to parotid glands. We here report an additional case of this rare association. CASE REPORT: A 66-year-old male with a background of type 2 diabetes mellitus and post-alcoholic decompensated liver cirrhosis presented with a progressively enlarging painful right facial swelling for 2 months that was eventually found to be due to hepatocellular carcinoma metastatic to the right parotid gland. Fine needle aspiration from the right parotid showed sheets and single malignant cells that were interpreted as carcinoma not otherwise specific. However, biopsy showed metastatic hepatocellular carcinoma into the right parotid gland. CONCLUSIONS: We report an additional case of the rare metastasis of hepatocellular carcinoma to the parotid glands. It should therefore be considered in a patient with decompensated liver cirrhosis presenting with a parotid swelling. Furthermore, the present case demonstrates the importance of the tissue biopsy for obtaining an accurate final diagnosis. PMID- 25129421 TI - In vitro fungicidal photodynamic effect of hypericin on Trichophyton spp. AB - Hypericin is a natural photosensitizer used in photodynamic therapy (PDT), which has shown in vitro antifungal effect against Candida spp. The aim of this study was to evaluate the in vitro fungicidal effect of hypericin-PDT on dermatophytes. Trichophyton rubrum and Trichophyton mentagrophytes strains were incubated with different concentrations of hypericin for different times and exposed to light emitting diode lamp (602 +/- 10 nm, 10.3 mW cm(-2), and fluence 37 J cm(-2)). Using the optimal incubation time, 60 min, a 3-log fungicidal effect was achieved with hypericin concentration ranges of 10-20 MUM for T. rubrum and 20-50 MUM for T. mentagrophytes (p = 0.95). Confocal fluorescence microscopy showed the localization of hypericin inside the dermatophytes diffusely distributed in the cytoplasm of conidia and hyphae and outside the nucleus. In conclusion, hypericin PDT has a fungicidal effect in vitro on dermatophytes. Hypericin seems to be a promising photosensitizer to treat localized dermatophytic infections such as tinea pedis and onychomycosis. PMID- 25129422 TI - Magnetic resonance enterography in pregnant women with Crohn's disease: case series and literature review. AB - BACKGROUND: Evaluation of pregnant women with known or suspected Crohn's disease (CD) remains a challenge. Magnetic Resonance Enterography (MRE) is a promising diagnostic tool in these patients; however, the clinical data on MRE utilization in pregnancy is scarce. The aim of the study was to describe the experience with MRE in pregnant CD patients in a tertiary referral center. METHODS: We retrospectively reviewed MRE studies performed in pregnant women with known or suspected CD that were performed between January 2007 and November 2012. Imaging findings, clinical management and outcome were extracted from patient's file and electronic records. Image quality was evaluated. RESULTS: Ten studies of 9 patients were included. MRE protocol was modified to maximize maternal and fetal safety, and intravenous gadolinium was not used. In 7 patients, CD diagnosis was previously established; six were admitted with clinical symptoms consistent with CD exacerbation, and an additional patient with a recurrent groin abscess without apparent luminal symptoms. In all seven patients, imaging features consistent with active CD were detected; new penetrating complications were detected in 4 patients. Two patients underwent MRE for suspected CD which was not comforted by study results. The clinical management was significantly impacted by MRE results in all positive cases. The image quality of the fast MRE sequences obtained without gadolinium was satisfactory and allowed meaningful interpretation. CONCLUSION: MRE with an adapted protocol for pregnancy is a reliable imaging modality to manage in pregnant women with known or suspected CD. PMID- 25129423 TI - The Postpartum Worry Scale-Revised: continuing validation with a sample of NICU mothers. AB - This study represents the second validation phase of the Postpartum Worry Scale Revised (PWS-R). As the PWS-R includes items tapping infant health and development concerns, we compare its psychometric properties with a sample of NICU mothers and the online sample used in the initial validation. We conduct a confirmatory factor analysis (CFA) to fit the latent factor structure previously validated with the online sample to the NICU sample. We also examine the reliability and construct validity of the PWS-R when used with a NICU sample. The PWS-R's reliability remains good and moderate concurrent correlations with theoretically similar constructs are shown with the newly created PWS-R factors. Model testing with the NICU sample reveals a different three factor structure than the four factor structure previously revealed with the online sample. The psychometric findings for the PWS-R provide continuing support for its use as a measure of postpartum worry; however, the differences in factor structure suggest that the PWS-R scores of high risk samples such as NICU parents should not be compared to those of community samples. Next steps in the iterative validation process and recommendations for use are considered, particularly with regard to high-risk samples. PMID- 25129424 TI - Austenite layer and precipitation in high Co-Ni maraging steel. AB - In high Co-Ni maraging steel, austenite has a great effect on the fracture toughness of the steel and the precipitated carbides are the main strengthening phase. In this study, both austenite layers and precipitation were observed and their formation theory was analyzed by Thermo-Calc simulation and several reported results. TEM and HRTEM observation results showed that the thickness of the austenite layers was about 5-10 nm and the length of the needle-like precipitated carbides was less than 10nm. The carbides maintained coherent or semi-coherent relation with the matrix. PMID- 25129425 TI - Looking forward to genetically edited fruit crops. AB - The availability of genome sequences for many fruit crops has redefined the boundaries of genetic engineering and genetically modified (GM) crop plants. However commercialization of GM crops is hindered by numerous regulatory and social hurdles. Here, we focus on recently developed genome-editing tools for fruit crop improvement and their importance from the consumer perspective. Challenges and opportunities for the deployment of new genome-editing tools for fruit plants are also discussed. PMID- 25129427 TI - There is hope in Pandora's box. PMID- 25129426 TI - Effect of preinjury warfarin use on outcomes after head trauma in Medicare beneficiaries. AB - BACKGROUND: Elderly Americans are at increased risk of head trauma, particularly fall related. The effect of warfarin on head trauma outcomes remains controversial. METHODS: Medicare beneficiaries with head injuries from 2009 to 2011 were identified by International Classification of Diseases (ICD)-9 code. Preinjury warfarin use was determined using Part D claims. Multiple logistic regression models determined the association of preinjury warfarin on need for hospitalization, intensive care unit care, and occurrence of intracranial hemorrhage. Association between warfarin and in-hospital mortality was assessed using a Cox proportional hazard model. RESULTS: Of 11,078 head injured patients, 5.2% were injured while on warfarin. Preinjury warfarin increased the odds of intracranial hemorrhage by 40% and doubled the risk of 30-day in-hospital mortality after adjusting for demographic and clinical factors. CONCLUSIONS: Warfarin at the time of head injury increases the risk of adverse outcomes in Medicare beneficiaries with head injuries. Caution should be used when initiating anticoagulation in elderly Americans at risk for trauma. PMID- 25129429 TI - Female military medical school graduates entering surgical internships: are we keeping up with national trends? AB - BACKGROUND: Ratios of women graduating from the only US military medical school and entering surgical internships were reviewed and compared with national trends. METHODS: Data were obtained from the Uniformed Services University of the Health Sciences graduation announcements from 2002 to 2012. RESULTS: There were 1,771 graduates from 2002 to 2012, with 508 female (29%) and 1,263 male (71%) graduates. Female graduates increased over time (21% to 39%; P = .014). Female general surgery interns increased from 3.9% to 39% (P = .025). Female overall surgical subspecialty interns increased from 20% in 2002 to 36% in 2012 (P = .046). Women were represented well in obstetrics (57%), urology (44%), and otolaryngology (31%), but not in neurosurgery, orthopedics, and ophthalmology (0% to 20%). CONCLUSIONS: The sex disparity between military and civilian medical students occurs before entry. Once in medical school, women are just as likely to enter general surgery or surgical subspecialty as their male counterparts. Increased ratio of women in the class is unlikely to lead to a shortfall except in specific subspecialties. PMID- 25129428 TI - Influence of adrenal pathology on perioperative outcomes: a multi-institutional analysis. AB - BACKGROUND: Endoscopic or open adrenalectomies are performed for variable pathologies. We investigated if adrenal pathology affects perioperative outcomes independent of operative approach. METHODS: A multi-institutional retrospective review of 345 adrenalectomies was performed. A multivariate analysis was utilized. RESULTS: Pathology groups included benign non-pheochromocytoma tumors (50.4%), pheochromocytomas (41%), adrenocortical carcinomas (5.2%), and metastatic tumors (3.4%). Controlling for age, body mass index, tumor size, procedure type, and pathology, pheochromocytomas exhibited greater blood loss (92 mL more, P = .007) and operative times (33 min more, P < .001) than benign non pheochromocytoma tumors. Metastatic tumors demonstrated longer operative times (53 min more, P = .013). Open adrenalectomy was associated with greater blood loss (396 mL more, P = .001), transfusion requirement (P = .021), operative times (79 min more, P < .001), hospital stay (6.6 days more, P < .001) and complications (P < .001) when compared with endoscopic adrenalectomy. CONCLUSIONS: The type of adrenal pathology appears to influence blood loss and operative time but not complications in patients undergoing adrenalectomy. Open adrenalectomy remains a major driver of adverse perioperative outcomes. PMID- 25129430 TI - Factors and outcomes associated with surgical treatment options of contralateral breast cancer. AB - BACKGROUND: The treatment for a contralateral breast cancer (CBC) presents a growing dilemma given the expanding number of long-term survivors. We hypothesize that there will be specific surgical treatment trends with demographic differences between the treatment groups. METHODS: The Surveillance, Epidemiology, and End Results (SEER) cancer database was queried to identify CBC patients from 1998 to 2010. Relevant data were compared among the surgical treatment groups of lumpectomy, mastectomy, and mastectomy/reconstruction. RESULTS: Of 1,534 patients, 31% underwent lumpectomy and 69% underwent mastectomy [201 (21%) mastectomy/reconstruction; 748 (69%) mastectomy alone]. Older patients (age >80 years) were more likely to undergo lumpectomy; those with larger tumors (T4) or node-positive disease more often underwent mastectomy. Overall survival was significantly higher in the mastectomy/reconstruction group (P = .05). CONCLUSIONS: Younger age, larger tumor size, and positive nodal disease were independently associated with mastectomy. As the number of long-term breast cancer survivors increases, factors contributing to CBC treatments must be studied to maximize survival potential. PMID- 25129431 TI - Malnutrition, sex ratio, and selection: a study based on the great leap forward famine. AB - This study tests the evolutionary hypothesis that maternal nutritional condition can influence offspring sex ratio at birth in humans. Using the 1959-1961 Chinese Great Leap Forward famine as a natural experiment, this study combines two large scale national data sources and difference-in-differences method to identify the effect of famine-induced acute malnutrition on sex ratio at birth. The results show a significant famine-induced decrease in the proportion of male births in the 1958, 1961, and 1964 in the urban population but not in the rural population. Given that both the urban and rural populations suffered from the famine-induced malnutrition, and that the rural population experienced a drastic famine-induced mortality increase and fertility reduction, these results suggest the presence of a short-term famine effect, a long-term famine effect, and a selection effect. The timing of the estimated famine effects suggests that famine influences sex ratio at birth by differential implantation and differential fetal loss by fetal sex. PMID- 25129432 TI - Psychomotor retardation is a scar of past depressive episodes, revealed by simple cognitive tests. AB - The cumulative duration of depressive episodes, and their repetition, has a detrimental effect on depression recurrence rates and the chances of antidepressant response, and even increases the risk of dementia, raising the possibility that depressive episodes could be neurotoxic. Psychomotor retardation could constitute a marker of this negative burden of past depressive episodes, with conflicting findings according to the use of clinical versus cognitive assessments. We assessed the role of the Retardation Depressive Scale (filled in by the clinician) and the time required to perform the neurocognitive d2 attention test and the Trail Making Test (performed by patients) in a sample of 2048 depressed outpatients, before and after 6 to 8 weeks of treatment with agomelatine. From this sample, 1140 patients performed the TMT-A and -B, and 508 performed the d2 test, at baseline and after treatment. At baseline, we found that with more past depressive episodes patients had more severe clinical level of psychomotor retardation, and that they needed more time to perform both d2 and TMT. When the analyses were performed again after treatment, and especially when the analyses were restricted to patients with clinical remission, the cognitive tests were the only ones correlated with past depressive episodes. Psychomotor retardation tested at a cognitive level was therefore systematically revealing the burden of past depressive episodes, with an increased weight for patients with less remaining symptoms. If prospectively confirmed, interventions such as cognitive remediation therapy could benefit from a more specific focus on neurocognitive retardation. PMID- 25129433 TI - Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production. AB - The high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC 145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV replication, HMGB1 promotes PRRSV-induced NF-kappaB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection. PMID- 25129435 TI - Kilham Rat Virus-induced type 1 diabetes involves beta cell infection and intra islet JAK-STAT activation prior to insulitis. AB - We used the LEW1.WR1 rat model of Kilham Rat Virus (KRV)-induced type 1 diabetes (T1D) to test the hypothesis that disease mechanisms are linked with beta cell infection and intra-islet immune activation prior to insulitis. KRV induces genes involved in type I and type II interferon pathways in islet cell lines in vitro and in islets from day-5-infected animals in vivo via mechanisms that do not involve insulitis, beta cell apoptosis, or impaired insulin expression. Immunohistochemistry studies indicated that KRV protein is expressed in beta cells 5 days following infection. KRV induces the phosphorylation of Janus Kinase 1/2 (JAK1/2) and signal transducer and activator of transcription 1 (STAT-1) in islet cells via a mechanism that could involve TLR9 and NF-kappaB pathways. These data demonstrate for the first time that KRV-induced islet destruction is associated with beta cell infection and intra-islet innate immune upregulation early in the disease process. PMID- 25129434 TI - Regulation of human genome expression and RNA splicing by human papillomavirus 16 E2 protein. AB - Human papillomavirus 16 (HPV16) is causative in human cancer. The E2 protein regulates transcription from and replication of the viral genome; the role of E2 in regulating the host genome has been less well studied. We have expressed HPV16 E2 (E2) stably in U2OS cells; these cells tolerate E2 expression well and gene expression analysis identified 74 genes showing differential expression specific to E2. Analysis of published gene expression data sets during cervical cancer progression identified 20 of the genes as being altered in a similar direction as the E2 specific genes. In addition, E2 altered the splicing of many genes implicated in cancer and cell motility. The E2 expressing cells showed no alteration in cell growth but were altered in cell motility, consistent with the E2 induced altered splicing predicted to affect this cellular function. The results present a model system for investigating E2 regulation of the host genome. PMID- 25129437 TI - The Cucumber leaf spot virus p25 auxiliary replicase protein binds and modifies the endoplasmic reticulum via N-terminal transmembrane domains. AB - Cucumber leaf spot virus (CLSV) is a member of the Aureusvirus genus, family Tombusviridae. The auxiliary replicase of Tombusvirids has been found to localize to endoplasmic reticulum (ER), peroxisomes or mitochondria; however, localization of the auxiliary replicase of aureusviruses has not been determined. We have found that the auxiliary replicase of CLSV (p25) fused to GFP colocalizes with ER and that three predicted transmembrane domains (TMDs) at the N-terminus of p25 are sufficient for targeting, although the second and third TMDs play the most prominent roles. Confocal analysis of CLSV infected 16C plants shows that the ER becomes modified including the formation of punctae at connections between ER tubules and in association with the nucleus. Ultrastructural analysis shows that the cytoplasm contains numerous vesicles which are also found between the perinuclear ER and nuclear membrane. It is proposed that these vesicles correspond to modified ER used as sites for CLSV replication. PMID- 25129436 TI - Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice. AB - Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-alpha/beta/gamma. Finally, direct vaccination of BALB/c mice with a single 20 MUg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. PMID- 25129438 TI - Removal of a small C-terminal region of JCV and SV40 large T antigens has differential effects on transformation. AB - The large T antigen (LT) protein of JCV and SV40 polyomaviruses is required to induce tumors in rodents and transform cells in culture. When both LTs are compared side-by-side in cell culture assays, SV40 shows a more robust transformation phenotype even though the LT sequences are highly conserved. A complete understanding of SV40's enhanced transforming capabilities relative to JCV is lacking. When the least conserved region of the LT proteins, the variable linker and host range region (VHR), was removed, changes in T antigen expression and cellular p53 post-translational modifications occurred, but interaction with the pRB pathway was unaffected. Transformation assessed by growth in low serum was reduced after VHR truncation of the SV40, but not the JCV, T antigen. Conversely, anchorage independent transformation was enhanced only by truncation of the JCV VHR. This is the first report to link the SV40 or JCV VHR region to transformation potential. PMID- 25129439 TI - Relationship between IL-10 expression and prognosis in patients with primary breast cancer. AB - This retrospective study was designed to investigate the relationship between the expression of IL-10, CD4, CD8, and FOXP3 and clinicopathological features and prognosis in breast cancer patients. The expression of IL-10, CD4, CD8, and FOXP3 was detected by immunohistochemistry. Staining intensity of only IL-10 was associated with disease-free survival and distance disease-free survival (P<0.05). Staining density of IL-10 in stromal cells was associated with overall survival and distance disease-free survival (P<0.05). IL-10 expression levels might be used as a prognostic indicator for the recurrence, metastasis, and survival of breast cancer patients. PMID- 25129440 TI - Down-regulation of HDAC5 inhibits growth of human hepatocellular carcinoma by induction of apoptosis and cell cycle arrest. AB - Histone deacetylases (HDACs) play a critical role in the proliferation, differentiation, and apoptosis of cancer cells. An obstacle for the application of HDAC inhibitors as effective anti-cancer therapeutics is that our current knowledge on the contributions of different HDACs in various cancer types remains scarce. The present study reported that the mRNA and protein levels of HDAC5 were up-regulated in human hepatocellular carcinoma (HCC) tissues and cells as shown by quantitative real-time PCR and Western blot. MTT assay and BrdU incorporation assay showed that the down-regulation of HDAC5 inhibited cell proliferation in HepG2, Hep3B, and Huh7 cell lines. Data from in vivo xenograft tumorigenesis model also demonstrated the anti-proliferative effect of HDAC5 depletion on tumor cell growth. Furthermore, the suppression of HDAC5 promoted cell apoptosis and induced G1-phase cell cycle arrest in HCC cells. On the molecular level, we observed altered expression of apoptosis-related proteins such as p53, bax, bcl 2, cyto C, and caspase 3 in HDAC5-shRNA-transfected cells. Knockdown of HDAC5 led to a significant up-regulation of p21 and down-regulation of cyclin D1 and CDK2/4/6. We also found that the down-regulation of HDAC5 substantially increased p53 stability and promoted its nuclear localization and transcriptional activity. Our study suggested that knockdown of HDAC5 could inhibit cancer cell proliferation by the induction of cell cycle arrest and apoptosis; thus, suppression of HDAC5 may be a viable option for treating HCC patients. PMID- 25129441 TI - Long non-coding RNA CARLo-5 is a negative prognostic factor and exhibits tumor pro-oncogenic activity in non-small cell lung cancer. AB - Despite recent advances in the management of non-small cell lung cancer (NSCLC), the prognosis of NSCLC is still relatively poor. Thus, it is of great importance to identify novel effective diagnostic and prognostic biomarker of NSCLC. A growing volume of literature has demonstrated the vital roles of long non-coding RNAs (lncRNAs) in cancer biology. Cancer-associated region long non-coding RNA (CARLo-5), a recently identified lncRNA, was initially characterized in colon cancer. However, little is known about its role in NSCLC. In the present study, a great upregulation of CARLo-5 was observed in cancer tissues compared to their adjacent normal tissues. Meanwhile, patients with high CARLo-5 expression have significantly poorer prognosis than those with low expression. Inhibition of CARLo-5 by siRNA suppressed the proliferation, migration, and invasion in NSCLC cell lines in vitro. In addition, silencing of CARLo-5 reversed the epithelial mesenchymal transition in NSCLC cell line. Our study suggests that CARLo-5 may represent a prognostic marker and a potential therapeutic target of NSCLC. PMID- 25129442 TI - Outcome of gemcitabine plus molecular targeted agent for treatment of pancreatic cancer: a meta-analysis of prospective phase III studies. AB - The aim of this study is to assess the clinical outcome of gemcitabine (GEM) plus molecular targeted agents (MTAs) for treatment of pancreatic cancer, in the purpose of providing fundamental data for clinical practice. Databases like PubMed, EMBASE, and MEDLINE, EMBASE and Cochrane Library were searched to retrieve phase III clinical randomized controlled trials related to GEM plus MTAs for pancreatic cancer (up to Oct 2013). Literatures were independently screened by two researchers according to the inclusion and exclusion criteria. Data were extracted and analyzed by using Stata 11.0 software. Total, 11 studies were included, involving 5,451 participants who were divided into GEM plus MTAs group (n=2,729) and GEM plus placebo group (n=2,722). There was no significant difference in overall survival, progression-free survival, response rate, complete response, partial response, and clinical benefit rate between two groups. Compared with GEM plus placebo group, stable disease of GEM plus MTAs group was significantly increased (risk ratios (RRs) =1.14, 95% confidence interval (CI) 1.04-1.21, P=0.003). Further subgroup analysis indicated that GEM plus epidermal growth factor receptor (EGFR) inhibitor use induced higher response rate and clinical benefit rate than GEM plus placebo group (RRs=1.19, 95% CI 1.09-1.31, P=0.000; RR=1.18, 95% CI 1.09-1.27, P=0.000). In addition, no significant difference in 3-4 grade adverse reactions (incidence, anemia rate, neutropenia rate, and thrombocytopenia rate) was identified between two groups. GEM plus MTAs may be effective and safe for stabilizing patients suffering advanced pancreatic cancer, especially EGFR inhibitor. PMID- 25129443 TI - Evaluation of squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM) and alpha-L-fucosidase (AFU) as novel diagnostic biomarkers for hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) surveillance lacks a reliable biomarker. Alpha fetoprotein (AFP) is the most widely used. However, not all HCCs secrete AFP. AFP may be elevated with cirrhosis in the absence of HCC. Serum alpha-L-fucosidase (AFU) and squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IgM) were found to be useful markers in diagnosing HCC. SCCA-IgM and AFU were assessed by ELISA technique; AFP was measured by enzyme chemiluminescence in serum of 40 patients with HCC, 30 patients with liver cirrhosis, and 20 healthy control participants to compare their accuracy in early diagnosis of HCC. Serum SCCA-IgM and AFU levels were significantly elevated in HCC group compared to cirrhotic group (P value<0.001 and <0.001, respectively). Receiver operating characteristic curve showed the optimal cutoff value for SCCA-IgM was 233 AU/ml with sensitivity 87.5% and specificity 66% and for AFU was 25 U/L with sensitivity 87.5% and specificity 98%. AFP cutoff value was 48 ng/mL with sensitivity of 70% and specificity of 53.3%. The simultaneous determination of AFP and SCCA-IgM activity increased the sensitivity to 92.5% and specificity to 62.1%. There were positive significant correlations between SCCA-IgM and each of AFU (r=0.296, P=0.005) and AFP (r=0.284, P=0.007) and no correlation between AFP and AFU. All markers did not correlate with the tumor size or affected by the Child score. The significant difference between SCCA-IgM and AFU levels among HCC and cirrhotic patients suggests their use as potential diagnostic tools and allows identifying a new group of HCC patients even in the absence of elevated AFP. PMID- 25129444 TI - Proteomic analysis of formalin-fixed paraffin-embedded glomeruli suggests depletion of glomerular filtration barrier proteins in two-kidney, one-clip hypertensive rats. AB - BACKGROUND: It is well known that hypertension may cause glomerular damage, but the molecular mechanisms involved are still incompletely understood. METHODS: In the present study, we used formalin-fixed paraffin-embedded (FFPE) tissue to investigate changes in the glomerular proteome in the non-clipped kidney of two kidney one-clip (2K1C) hypertensive rats, with special emphasis on the glomerular filtration barrier. 2K1C hypertension was induced in 6-week-old Wistar Hannover rats (n = 6) that were sacrificed 23 weeks later and compared with age-matched sham-operated controls (n = 6). Tissue was stored in FFPE tissue blocks and later prepared on tissue slides for laser microdissection. Glomeruli without severe morphological damage were isolated, and the proteomes were analysed using liquid chromatography-tandem mass spectrometry. RESULTS: 2K1C glomeruli showed reduced abundance of proteins important for slit diaphragm complex, such as nephrin, podocin and neph1. The podocyte foot process had a pattern of reduced abundance of transmembrane proteins but unchanged abundances of the podocyte cytoskeletal proteins synaptopodin and alpha-actinin-4. Lower abundance of important glomerular basement membrane proteins was seen. Possible glomerular markers of damage with increased abundance in 2K1C were transgelin, desmin and acyl-coenzyme A thioesterase 1. CONCLUSIONS: Microdissection and tandem mass spectrometry could be used to investigate the proteome of isolated glomeruli from FFPE tissue. Glomerular filtration barrier proteins had reduced abundance in the non-clipped kidney of 2K1C hypertensive rats. PMID- 25129446 TI - Transport priorities, risk perception and worry associated with mode use and preferences among Norwegian commuters. AB - There is currently scant research on the role of transport priorities, risk perception and worry for travel mode use and preferences. The present study aims to examine these factors in relation to mode use and preferences among Norwegian commuters. A web-based survey was conducted in a randomly obtained representative sample of daily commuters in the extended greater Oslo area (n=690). The results showed that those who prioritized efficiency and flexibility tended to commute by car, while those who prioritized safety and comfort used public (e.g. metro, tram, and train) or active (e.g. walking and cycling) transport. In a free choice scenario, the respondents who prioritized flexibility reported a preference for using a car, whereas those who prioritized safety and comfort preferred public and active transport for their commuter travels. Risk perception of high impact events, such as terrorism and major accidents, as well as risk perception related to personal impact risks (theft, violence etc.) were related to car use on commuter travels. Transport-related worry exerted weak influences on mode use and preferences. Increased speed on rail transport and more frequent departures may be effective in reducing car use on commuter travels. Risk communication should focus on highlighting the low risk of experiencing security and safety issues in the public transport sector, and this message should be complemented by efforts to reduce the probability of negative events affecting public transport. PMID- 25129445 TI - Fluoxetine modulates breast cancer metastasis to the brain in a murine model. AB - BACKGROUND: Despite advances in the treatment of primary breast tumors, the outcome of metastatic breast cancer remains dismal. Brain metastases present a particularly difficult therapeutic target due to the "sanctuary" status of the brain, with resulting inability of most chemotherapeutic agents to effectively eliminate cancer cells in the brain parenchyma. A large number of breast cancer patients receive various neuroactive drugs to combat complications of systemic anti-tumor therapies and to treat concomitant diseases. One of the most prescribed groups of neuroactive medications is anti-depressants, in particular selective serotonin reuptake inhibitors (SSRIs). Since SSRIs have profound effects on the brain, it is possible that their use in breast cancer patients could affect the development of brain metastases. This would provide important insight into the mechanisms underlying brain metastasis. Surprisingly, this possibility has been poorly explored. METHODS: We studied the effect of fluoxetine, an SSRI, on the development of brain metastatic breast cancer using MDA-MB-231BR cells in a mouse model. RESULTS: The data demonstrate that fluoxetine treatment increases the number of brain metastases, an effect accompanied by elevated permeability of the blood-brain barrier, pro-inflammatory changes in the brain, and glial activation. This suggests a possible role of brain-resident immune cells and glia in promoting increased development of brain metastases. CONCLUSION: Our results offer experimental evidence that neuroactive substances may influence the pathogenesis of brain metastatic disease. This provides a starting point for further investigations into possible mechanisms of interaction between various neuroactive drugs, tumor cells, and the brain microenvironment, which may lead to the discovery of compounds that inhibit metastasis to the brain. PMID- 25129447 TI - Vaccination and malaria prophylaxis among Greek international travelers to Asian destinations. AB - BACKGROUND: International travel is rapidly increasing worldwide, and the greatest increases have occurred in tropical and subtropical areas. The aim of the survey was to investigate the pre-travel health-seeking practices of travelers to Asian destinations. METHODS: A questionnaire-based survey was conducted at the Athens International Airport between the 1st of November 2011 and the 30th of April 2013. RESULTS: A total of 1666 adult travelers participated in the study, and 69.7% were men. The mean age of the participants was 39 years. Previous travel to tropical countries was reported by 69% of the participants. The most frequent destination was the Indian subcontinent (45.0%). The main reasons for travel were visiting friends and relatives (VFRs; 36.5%) and business (32.4%). Most of the participants traveled for <1 month (51.4%). Only 24.5% pursued pre-travel consultations. Vaccinations were administered to 14.4% of the participants, and of those, 77%, 73%, and 32.5% received hepatitis A, tetanus/diphtheria, and typhoid vaccines, respectively. Malaria prophylaxis was given to 12.2% of the participants. Logistic regression analysis revealed that being male and unemployed, having an elementary level of education, traveling to visiting friends and relatives, and short durations of travel were significant determinants of not seeking pre-travel consultations. CONCLUSION: Significant gaps were revealed in the vaccinations and malaria prophylaxes of travelers departing to Asia. Specific educational tools should be developed to improve the awareness of travelers to high-risk destinations. PMID- 25129448 TI - A multicenter point-prevalence survey of antibiotic use in 13 Chinese hospitals. AB - BACKGROUND: The use of antibiotics is considered a major determinant of the development of resistance in organisms. This study assessed current patterns of antibiotic prescription and provides background for quality improvement in general hospitals in Hubei, China. METHODS: A point-prevalence study was performed in November 2008. All inpatients on the day of the survey were included in the analysis. RESULTS: On the day of the study, 6904 patients (56%) were receiving antibiotic therapy; the highest rate occurred in the ICU (90%), and the lowest occurred in the medical wards (39%). The most commonly used antibiotics were beta-lactam antibiotics, including cephalosporins (40%) and piperacillin (19%), followed by fluoroquinolones (14%). CONCLUSIONS: Our data indicated a high rate of antibiotic use in Chinese hospitals. These findings suggest important areas for intervention and the implementation of antibiotic stewardship policies in Chinese hospitals. A multi-faceted strategy should be implemented at the national level in China and should include education, regulation, and greater financial support from the government. PMID- 25129449 TI - Response of the seagrass Posidonia oceanica to different light environments: Insights from a combined molecular and photo-physiological study. AB - Here we investigated mechanisms underlying the acclimation to light in the marine angiosperm Posidonia oceanica, along its bathymetric distribution (at -5 m and 25 m), combining molecular and photo-physiological approaches. Analyses were performed during two seasons, summer and autumn, in a meadow located in the Island of Ischia (Gulf of Naples, Italy), where a genetic distinction between plants growing above and below the summer thermocline was previously revealed. At molecular level, analyses carried out using cDNA-microarray and RT-qPCR, revealed the up-regulation of genes involved in photoacclimation (RuBisCO, ferredoxin, chlorophyll binding proteins), and photoprotection (antioxidant enzymes, xanthophyll-cycle related genes, tocopherol biosynthesis) in the upper stand of the meadow, indicating that shallow plants are under stressful light conditions. However, the lack of photo-damage, indicates the successful activation of defense mechanisms. This conclusion is also supported by several responses at physiological level as the lower antenna size, the higher number of reaction centers and the higher xanthophyll cycle pigment pool, which are common plant responses to high-light adaptation/acclimation. Deep plants, despite the lower available light, seem to be not light-limited, thanks to some shade-adaptation strategies (e.g. higher antenna size, lower Ek values). Furthermore, also at the molecular level there were no signs of stress response, indicating that, although the lower energy available, low-light environments are more favorable for P. oceanica growth. Globally, results of whole transcriptome analysis displayed two distinct gene expression signatures related to depth distribution, reflecting the different light-adaptation strategies adopted by P. oceanica along the depth gradient. This observation, also taking into account the genetic disjunction of clones along the bathymetry, might have important implications for micro evolutionary processes happening at meadow scale. Further investigations in controlled conditions must be performed to respond to these questions. PMID- 25129450 TI - How to minimize lymphoceles and treat clinically symptomatic lymphoceles after radical prostatectomy. AB - The development of a lymphocele after pelvic surgery is a well-documented complication, especially where pelvic lymph node dissection (PLND) is part of the operation. However, not all lymphoceles are symptomatic and require treatment. Most lymphoceles spontaneously resolve, and even lymphoceles that become symptomatic may resolve without any intervention. Robotic assisted radical prostatectomy (RARP) is a common operation in urology where PLND is likely to be performed in intermediate and high-risk prostate cancer patients. The rationale for performing a PLND in prostate cancer is for accurate staging and potential therapeutic benefits. However, due to potential intraoperative and postoperative complications there is still a debate regarding the value of PLND in prostate cancer. In this review, we will discuss the potential risk factors to be aware of in pelvic surgery in order to minimize the formation of a lymphocele, along with the management for clinically significant lymphoceles. PMID- 25129451 TI - Effect of ecto-5'-nucleotidase (eN) in astrocytes on adenosine and inosine formation. AB - ATP is a gliotransmitter released from astrocytes. Extracellularly, ATP is metabolized by a series of enzymes, including ecto-5'-nucleotidase (eN; also known as CD73) which is encoded by the gene 5NTE and functions to form adenosine (ADO) from adenosine monophosphate (AMP). Under ischemic conditions, ADO levels in brain increase up to 100-fold. We used astrocytes cultured from 5NTE (+/+) or 5NTE (-/-) mice to evaluate the role of eN expressed by astrocytes in the production of ADO and inosine (INO) in response to glucose deprivation (GD) or oxygen-glucose deprivation (OGD). We also used co-cultures of these astrocytes with wild-type neurons to evaluate the role of eN expressed by astrocytes in the production of ADO and INO in response to GD, OGD, or N-methyl-D-aspartate (NMDA) treatment. As expected, astrocytes from 5NTE (+/+) mice produced adenosine from AMP; the eN inhibitor alpha,beta-methylene ADP (AOPCP) decreased ADO formation. In contrast, little ADO was formed by astrocytes from 5NTE (-/-) mice and AOPCP had no significant effect. GD and OGD treatment of 5NTE (+/+) astrocytes and 5NTE (+/+) astrocyte-neuron co-cultures produced extracellular ADO levels that were inhibited by AOPCP. In contrast, these conditions did not evoke ADO production in cultures containing 5NTE (-/-) astrocytes. NMDA treatment produced similar increases in ADO in both 5NTE (+/+) and 5NTE (-/-) astrocyte-neuron co-cultures; dipyridamole (DPR) but not AOPCP inhibited ADO production. These results indicate that eN is prominent in the formation of ADO from astrocytes but in astrocyte neuron co-cultures, other enzymes or pathways contribute to rising ADO levels in ischemia-like conditions. PMID- 25129452 TI - Regional differences between US and Europe in radiological osteoarthritis and self assessed quality of life in patients undergoing total hip arthroplasty surgery. AB - Precise indications for THA remain unclear and regional differences might exist in selecting patients for surgery. In this study we investigate radiological OA grade and self-reported quality of life in 909 patients undergoing THA in 16 centers across US and Europe. Patients in US were younger and had higher BMI. More patients with mild Tonnis OA grade underwent surgery in the US compared to Europe. Patients in the US had significantly higher pain VAS and significantly lower SF-36 Physical, while having significantly higher EQ-VAS scores preoperatively. Patient demographics and disease severity according to radiological OA grade and self-reported survey scores vary between the United States and Europe. This knowledge can be used in the interpretation of US and European based studies on outcome following THA. PMID- 25129453 TI - The impact of community support initiatives on the stigma experienced by people living with HIV/AIDS in South Africa. AB - In the current context of human resource shortages in South Africa, various community support interventions are being implemented to provide long-term psychosocial care to persons living with HIV/AIDS (PLWHA). However, it is important to analyze the unintended social side effects of such interventions in regards to the stigma felt by PLWHA, which might threaten the successful management of life-long treatment. Latent cross-lagged modeling was used to analyze longitudinal data on 294 PLWHA from a randomized controlled trial (1) to determine whether peer adherence support (PAS) and treatment buddying influence the stigma experienced by PLWHA; and (2) to analyze the interrelationships between each support form and stigma. Results indicate that having a treatment buddy decreases felt stigma scores, while receiving PAS increases levels of felt stigma at the second follow up. However, the PAS intervention was also found to have a positive influence on having a treatment buddy at this time. Furthermore, a treatment buddy mitigates the stigmatizing effect of PAS, resulting in a small negative indirect effect on stigma. The study indicates the importance of looking beyond the intended effects of an intervention, with the goal of minimizing any adverse consequences that might threaten the successful long-term management of HIV/AIDS and maximizing the opportunities created by such support. PMID- 25129455 TI - Evaluation of TAZ expression and its effect on tumor invasion and metastasis in human glioma. AB - OBJECTIVES: To evaluate the expression of TAZ and its role in tumor invasion and metastasis in human glioma. METHODS: The expression of TAZ protein was measured in 48 samples of surgically resected human glioma and 13 samples of normal brain tissues using immunohistochemistry. TAZ was knocked down by a retrovirus-mediated TAZ shRNA in a glioma cell line, SNB19. Transwell cell migration and invasion assays were used to determine migration and invasion of SNB19 cells. RESULTS: The positive expression rate of TAZ protein in glioma tissues was significantly higher than that in normal brain tissues (79.2% vs. 15.4%, P<0.001). Furthermore, clinical analysis suggested that the positive expression rate of TAZ protein in poorly differentiated tumor tissues was significantly higher as compared with that in well differentiated tissues (96.0% vs. 60.9%, P<0.01). TAZ was significantly knocked down by TAZ shRNA (P<0.001), and TAZ knockdown significantly reduced cell migration and invasion (P<0.01, respectively) in SNB19 cells. CONCLUSIONS: TAZ protein overexpression is observed in human glioma and its elevated expression is significantly correlated with poor differentiation. TAZ knockdown prominently reduces cell migration and invasion in SNB19 cells, suggesting that TAZ may play a key role in the initiation and progression of human glioma. PMID- 25129454 TI - Looking Beyond Health-Related Quality of Life: Predictors of Subjective Well Being among People Living with HIV in the Netherlands. AB - Health care interventions are increasingly expected to improve subjective well being (SWB) rather than health-related quality of life (HRQOL) only. However, little is known about how HRQOL and other relevant quality of life (QOL) domains relate to SWB among people living with HIV. People living with HIV treated in Dutch HIV centers (n = 191) completed a cross-sectional survey on SWB, HRQOL, and other QOL domains (social, financial, sexual, and environmental well-being). In bivariate analyses, all QOL domains were significantly related to SWB (r = .17 to .42). In structural equation models, physical health (beta = .14; p < .05), mental health (beta = .27; p < .01), and environmental well-being (beta = .41; p < .01) directly predicted SWB, while financial and social well-being explained SWB indirectly. Thus, environmental well-being and mental health are the main predictors of SWB, and physical health, social well-being, and financial well being to a lesser extent. Given that most of HIV-care is directed at improving physical health, from the perspective of promoting SWB HIV care should also be directed at other life domains. PMID- 25129456 TI - Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma. AB - OBJECTIVES: To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma (CSCC). METHODS: Using retrospective analysis, 73 cases of CSCC were selected from Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, which were removed between January 2000 and January 2012. It was considered as experimental group. Meanwhile, 11 cases of normal skin specimens of non tumor patients were selected as control group. The expression level of c-fos and c-myc was compared in the two groups. RESULTS: The expressions of c-fos [72.60% (53/73)] and c-myc [83.56% (61/73)] in experimental group were statistically significant (P<=0.05) compared with control group (0%). Expression of c-myc protein was negatively related to differentiation of CSCC. The difference was statistically significant (chi(2)=7.26, P=0.001<0.05). While expression of c-fos protein was positively related to differentiation of CSCC, which was statistically significant (chi(2)=7.47, P=0.001 2<0.025). CONCLUSIONS: The expression level of c-fos and c myc can be used as an important indicator of CSCC differentiation, and it has closely connection with the differentiated degree, which can guide clinical prognosis. PMID- 25129457 TI - HTRA1 gene expression in gastric epithelial cells. AB - OBJECTIVES: To explore HtrA1 gene expression and its regulation in human gastric cancers. METHODS: The HtrA1 mRNA levels were examined by QPCR analysis and confirmed its expression with Northern blot analysis. The HtrA1 protein levels in all six gastric epithelial cell lines were investigated by Western blot analysis. Gene copy number was accessed and then sequenced the coding region from each mRNA in all six cell lines. The HtrA1 promoter region DNA methylation status was detected by using bisulfite sequencing analysis. Effect of decitabine and TSA on HTRA1 expression in gastric cancer cell line was determined by RTPCR. RESULTS: HIC analysis indicated that HtrA1 was highly expressed in normal epithelium, but dramatically down-regulated in gastric carcinoma tissues and variably expressed in tumor-adjacent tissues. HtrA1 gene expression was dramatically decreased in gastric carcinoma cells compared to non-tumorigenic counterparts. The HtrA1 gene loss in any of the 4 breast cancer cell lines was not detected. Total 14 CpGs in this region were all methylated in gastric cancer cells, whereas two normal cells, GES-1 and HFI-145, were having several unmethylated cytosines in this region. HtrA1 showed as ~Mr 44,000, Expression of HtrA1 protein was not observed in any of the four gastric cancer cell lines, BGC-823, MKN-45, SGC-7901and MKN 28. HtrA1 expression was observed in the HFI-145and GES-1 cell lines. CONCLUSIONS: The epigenetic silencing for HtrA1 gene expression could provide a possible strategy for re-activating HtrA1 gene expression in gastric cancer cells, thus facilitating further investigation of HtrA1's role in chemotherapy. PMID- 25129458 TI - Influence of As2O3 combined with ginsenosides Rg3 on inhibition of lung cancer NCI-H1299 cells and on subsistence of nude mice bearing hepatoma. AB - OBJECTIVES: To study the effect of arsenic trioxide (As2O3) combined with ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in nude mice bearing hepatoma. METHODS: MTT method was used to measure the inhibition effect of As2O3 combined Rg3 on NCI-H1299 cells, and the proliferation inhibiting effect was observed via establishing the transplanted tumor model in vitro. A total of 40 tumor-bearing nude mice were randomly divided into normal saline group, As2O3, Rg3 and As2O3+Rg3 group. Transplantation tumor model of lung cancer in nude mice was constructed, followed by injection of certain concentrations of normal saline, As2O3, ginseng saponin Rg3 and As2O3+Rg3 every day. The survival duration and the tumors size of the mice were recorded and the Kaplan-Meier curve was made; microscopic observation of apoptosis of tumor cells in vivo was done using TUNEL staining. RESULTS: After 72 h of injection, inhibition rate of tumor cell in normal saline group, As2O3 group, Rg3 group and As2O3+Rg3 group was (5.66+/-0.31)%, (65.58+/-4.75)%, (44.69+/-3.32)% and (82.67+/ 5.43)%, respectively. Inhibition rate of tumor cell in As2O3 group, Rg3 group and As2O3+Rg3 group was significantly higher than that of normal saline group (P<0.01); inhibition rate of tumor cells of As2O3+Rg3 group was significantly higher than that of the two groups given As2O3 or Rg3 alone (P<0.01). The tumor volume of As2O3 group, Rg3 group and As2O3+Rg3 group shrank to (65.38+/-3.25)%, (77.68+/-3.43)% and (42.65+/-3.55)% of the original, tumor volume of saline group was 1.21 times of the original size (P<0.01); Median survival of saline group, Rg3 group, As2O3 group were significantly shorter than that of As2O3+Rg3 group (P<0.01); co-ordinated intervention ability of As2O3+Rg3 on NCI-H1299 cell was significantly higher than that of As2O3 or Rg3, separately. CONCLUSIONS: As2O3 combined with Rg3 can significantly inhibit proliferation of NCI-H1299 cells in lung cancer, prolong survival of tumor-bearing nude mice, and promote tumor cell apoptosis, and have significant effect on lung cancer treatment. PMID- 25129459 TI - MicroRNA-184 promotes proliferation ability of glioma cells by regulating FOXO3. AB - OBJECTIVES: To investigate the effect of microRNA (miR-184) on regulating the genesis, development and proliferation of glioma cells. METHODS: Lipidosome was used to transfect miR-184 mimic and inhibitor to glioma cell line, and the cell proliferation ability changes were determined by MTT and plate cloning experiment after the transfection. WB test was used to measure the levels of cyclinD1, p27 and FOXO3. Meanwhile, QPCR was used to detect miR-184 expression in glioma cell line, glioma tissues and adjacent tissues. Luciferase experiment was used to test 3'UTR gene targeting regulation of miR-184 and FOXO3. RESULTS: QPCR results showed a significant lower miR-184 expression level in glioma cell line and glioma tissues than that in juxtacancerous tissue. MTT and plate cloning experiments have shown that after over-expressing of miR-184, the cell proliferation capacity of glioma U87 and T98G was significantly increased, which was significantly inhibited after the inhibition of miR-184. WB results showed a lower expression level of p27 in U87 and T98G cells, and a higher expression level of cyclinD1 after over-expressing of miR-184 was observed. However, a lower expression level of cyclinD1 and a higher expression level of p27 after the inhibition of miR-184. The luciferase activity was inhibited after the over expressing of miR-184. CONCLUSIONS: MiR-184 can affect the proliferation abilities of glioma cells and regulate the cell cycle related protein. It plays an important role in the occurrence and development of gliomas. PMID- 25129460 TI - Lentivirus vectors construction of SiRNA targeting interference GPC3 gene and its biological effects on liver cancer cell lines Huh-7. AB - OBJECTIVES: To build GPC3 gene short hairpin interference RNA (shRNA) slow virus vector, observe expression of Huh-7 GPC3 gene in human liver cell line proliferation apoptosis and the effect of GPC3 gene influencing on liver cancer cell growth, and provide theoretical basis for gene therapy of liver cancer. METHODS: Hepatocellular carcinoma cell line Huh-7 was transfected by a RNA interference technique. GPC3 gene expression in a variety of liver cancer cell lines was detected by fluorescence quantitative PCR. Targeted GPC3 gene sequences of small interfering RNA (siRNA) PGC-shRNA-GPC3 were restructured. Stable expression cell lines of siRNA were screened and established with the help of liposomes (lipofectamine(TM2000)) as carrier transfection of human liver cell lines. In order to validate siRNA interference efficiency, GPC3 siRNA mRNA expression was detected after transfection by using RT-PCR and Western blot. The absorbance value of the cells of blank group, untransfection group and transfection group, the cell cycle and cell apoptosis were calculated, and effects of GPC3 gene on Huh-7 cell proliferation and apoptosis were observed. RESULTS: In the liver cancer cell lines Huh-7, GPC3 gene showed high expression. PGC-shRNA-GPC3 recombinant plasmid was constructed successfully via sequencing validation. Stable recombinant plasmid transfected into liver cancer cell lines Huh-7 can obviously inhibit GPC3 mRNA expression level. CONCLUSIONS: The targeted GPC3 siRNA can effectively inhibit the expression of GPC3. PMID- 25129461 TI - Effect of Fibulin-5 on cell proliferation and invasion in human gastric cancer patients. AB - OBJECTIVES: To explore the effect of Fibulin-5 expression on cell proliferation and invasion in human gastric cancer patients. METHODS: Fibulin-5 expression was detected in 56 samples of surgically resected gastric cancer and paired noncancerous tissues using qRT-PCR and immunoblotting. Fibulin-5 was knocked down by Fibulin-5 shRNA in MGC-803 cells, then BrdU cell proliferation and transwell invasion assays were used to determine cell proliferation and invasion. RESULTS: The level of Fibulin-5 mRNA in gastric cancer tissues was significantly higher as compared with that in normal tumor-adjacent tissues (P<0.05). Otherwise, the level of Fibulin-5 protein in cancer and noncancerous tissues was consistent with mRNA expression (P<0.05). Fibulin-5 protein expression in tumor tissues with poorly differentiated, lymph node metastasis and advanced TNM tumor stage was significantly higher (P<0.05, respectively). Fibulin-5 was obviously knocked down by Fibulin-5 shRNA (P<0.05), and Fibulin-5 knockdown significantly inhibited cell proliferation and invasion in MGC-803 cells (P<0.05, respectively). CONCLUSIONS: The high-expression of Fibulin-5 is associated with the malignant clinicopathologic parameters in gastric cancer and Fibulin-5 knockdown inhibits cell proliferation and invasion in MGC-803 cells, suggesting Fibulin-5 may act as a key factor in the progression of gastric cancer. PMID- 25129462 TI - Effect of simvastatin on expression of IL17, HMGB1 and TLR4 in LN kidney tissues of rats. AB - OBJECTIVES: To observe the intervention influence and effect of simvastatin on the expression of interleukin 17 (LI17), high mobility group protein 1 (HMGB1) and TLR4 path in Lupus nephritis (LN) rats. METHODS: A total of 28 BSXSB male mice with LN (16 weeks) were randomly divided into observation group and the comparison group, observation group was given 6 mg*kg(-1)*d(-1) simvastatin in 0.1% PBS lavage for 4 weeks, the comparison group was not given any treatment. Blood urea nitrogen (BUN) level and urine trace albumin (Scr) level of two groups were determined. The expression of IL17, HMGB1 and TLR4 protein was detected using immune histochemical method, and the kidney histological damage was observed. RESULTS: BNU, LI17, HMGB1, TLR4 protein and HMGB1 mRNA in observation group was significantly lower than that in control group (P<0.05); There was no statistical difference of Scr level between two groups (P>0.05). Histological observation showed glomerular lesions integral of observation group was obviously lower than that of control group. CONCLUSIONS: Simvastatin can reduce the expression of IL17, HMGB1 and TLR4 protein in LN mice, thereby can inhibit the autoimmune response as a potential treatment function of LN. PMID- 25129463 TI - To investigate the effect of osteoporosis and intervertebral disc degeneration on the endplate cartilage injury in rats. AB - OBJECTIVES: To investigate the effect of osteoporosis and intervertebral disc degeneration on the endplate cartilage injury in rats. METHODS: A total of 48 female Sprague Dawley rats (3 months) were randomly divided into Groups A, B, C and D with 12 rats in each group. Osteoporosis and intervertebral disc degeneration composite model, simple degeneration model and simple osteoporosis model were prepared in Groups A, B and C respectively. After modeling, four rats of each group at 12th, 18th and 24th week were sacrificed. Intervertebral height of cervical vertebra C6/C7 was measured. Micro-CT was used to image the endplate of cephalic and caudal cartilage at C6/C7 intervertebral disc. Abraded area rate of C6 caudal and C7 cephalic cartilage endplate was calculated, and then C6/C7 intervertebral disc was routinely embedded and sectioned, stained with safranin O to observe histological changes microscopically. RESULTS: At 12, 18 and 24 weeks, intervertebral disc height of C6/C7 were (0.58+/-0.09) mm, (0.53+/-0.04) mm and (0.04+/-0.06) mm in Group A rats, (0.55+/-0.05) mm, (0.52+/-0.07) mm and (0.07+/ 0.05) mm in Group B rats. At 24th week, intervertebral disc height of Group A rats was significantly lower than that of Group B rats (P<0.05); intervertebral disc height of Groups A and B rats at each time point were significantly lower than that of Groups C and D (P<0.05). There was no significantly statistical difference of intervertebral disc height between Groups C and D (P>0.05). At 12 and 18 weeks, the abraded rate of C6 caudal and C7 cephalic cartilage endplate in Group A rats were significantly higher than that in Groups B, C and D rats (P<0.05); the abraded rate in Group B was significantly higher than that in Groups C and D (P>0.05). Microscopic observation of CT showed that ventral defects in C6 caudal or C7 cephalic cartilage endplate in Groups A and B appeared after 12 weeks of modeling; obvious cracks were found in front of the C6 and C7 vertebral body, and cartilage defect shown the trend of "repairing" at 18 and 24 weeks after modeling. CONCLUSIONS: Intervertebral disc degeneration and osteoporosis can cause damage to the cartilage endplate. Co-existence of these two factors can induce more serious damage to the endplate, which has possitive correlation with intervertebral disc degeneration. Osteoporosis plays a certain role in intervertebral disc degeneration process, and accelerates the degeneration of intervertebral disc in a specific time window. PMID- 25129464 TI - Effects of aspirin on fracture healing in OPF rats. AB - OBJECTIVES: To study the effect of aspirin on healing process of osteoporotic fracture (OPF) in rats. METHODS: A total of 50 female Wistar rats aged 3 months were randomly divided into observation group and control group, castration method was adopted to establish the osteoporosis (OP) model. After artificial preparing fractures on the midpoint of left femur, fixing gram needle intramedullary, OPF modeling was complete. Aspirin lavage of 33 mg once a day was adopted in observation group after modeling, same amount of normal saline was used in the control as placebo. From each group, selected 5 rats at the 2nd, 4th, 8th and 12th week after modeling to measure the bone mineral density (BMD) and histological examination of the fracture callus, radiology observation was conducted at the 8th and 12th week. Left femur biomechanical measurement was taken at the 12th week. RESULTS: BMD values of observation group at each time point were significantly higher than that of the control group after modeling (P<0.05); Histological observation showed that at the 8th week, the endochondral ossification process of observation group was faster than that of observation group, with fuzzy fracture line in observation group and clear fracture line in observation group; at the 12th week, fracture line disappeared in observation group, fracture line of the control group was fuzzy at the same time; three-point bending load of the left femur in observation group rats was significantly higher than that of control group after 12 weeks (P<0.05). CONCLUSIONS: Aspirin can accelerate the healing of new callus in OPF rats, increase bone density and biomechanics strength, and promote fracture healing of osteoporotic rats. PMID- 25129465 TI - Nerve protective effect of Baicalin on newborn HIBD rats. AB - OBJECTIVES: To investigate the nerve protective effect and mechanism of baicalin on newborn rats with hypoxic ischemic brain damage (HIBD). METHODS: A total of 64 SD newborn rats were randomly divided into control group, model group, nerve growth factor group and baicalin group, with 16 in each group. Left carotid artery ligation method was adopted to establish the HIBD model except for in control group, which was treated with intraperitoneal injection of salin e10 mL/kg for 3 d. After oxygen recovery on hypoxia ischemia rats, intraperitoneal injection of saline 10 mL/kg was adopted in model group for 3 d. Intraperitoneal injection of nerve growth factor injection 50 MUg/kg per day was adopted in nerve growth factor group for 3 d; intraperitoneal injection of radix scutellariae 16 mg/kg per day was adopted in baicalin group for 3 d after modeling. Four rats of each group were sacrificed at Day 1, 2, 3, 7 for microscopic observation of pathological morphological changes in brain tissue after HE staining, S-P immunohistochemical method was used for observation of Fas and FasL expression in brain cells. RESULTS: Neat structure of cells was observed in control group; edema cells in disordered arrangement was observed in model group, with some cells necrosis and cavity change; tissue injury in nerve growth factor group and baicalin group was significantly lighter than that in model group; Fas and FasL expression in model group, nerve growth factor group and baicalin group were significantly higher than that in control group at different time points (P<0.05); Fas and FasL expression in nerve growth factor group and baicalin group were significantly lower than that in model group at different time points (P<0.05); There was no statistical difference of Fas, FasL expression at each time point between nerve growth factor group and baicalin group (P>0.05). CONCLUSIONS: Baicalin can reduce expression of Fas and FasL in HIBD rats, inhibit apoptosis of nerve cells, thus achieve the protective effect on HIBD rat nerves. PMID- 25129466 TI - H nuclear magnetic resonance-based metabolomics reveals sex-specific metabolic changes of gastrodin intervention in rats. AB - OBJECTIVES: To explore (1)H nuclear magnetic resonance-based metabolomics on sex specific metabolic changes of gastrodin intervention in rats. METHODS: In this research, (1)H NMR-based metabolomics was used for the first time to investigate metabolic changes following chronic intervention with gastrodin in rats. RESULTS: 24 endogenous metabolites were identified. Body weight, daily diet and the total volume of urine in in each day of each rat were measured synchronously. Modifications in 12 metabolites were observed following gastrodin intervention, indicating gastrodin-induced alterations in carbohydrate and energy metabolism. Interestingly, these metabolic changes were not totally identical in female and male rats. Some metabolic changes arising from gastrodin intervention showed sexual dimorphism including LDL/VLDL and lactate which were on the decrease in the female but on the increase in the male, together with arginine/ornithine, creatine, and glycerol which were on the increase in the female but on the decrease in the male. While the decrease in pyruvate, succinate and glutamate was only shown in the male and the increase in valine, alpha-ketoglutarate, glycine and glucose was only in the female. CONCLUSIONS: This research shows the sex specific metabolic response to GAS intervention, weather GAS is a healthy dietary supplement for the male merits further investigation. PMID- 25129467 TI - Protective effect of pioglitazone on kidney injury in diabetic rats. AB - OBJECTIVES: To investigate the protective effect of pioglitazone on kidney injury in diabetic rat model and its mechanisms. METHODS: Forty healthy Sprague Dawley rats were selected and randomly divided into five groups, with 8 rats in each group. Group A served as control group and were administered with sterile citrate buffer (i.p.) as placebo. Groups B, C, D and E rats were injected (i.p.) with streptozotocin to induce type I diabetes. Diabetic rats in Group B were intragastrically administered with sterile saline solution alone. Groups C, D and E rats were intragastrically given pioglitazone hydrochloride suspension at doses of 10, 20, 30 mg/kg per day, respectively. After eight weeks of treatment, all rats were anesthetized and blood was withdrawn from the abdominal aortic for detection of hemoglobin A1c, serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Rats were then sacrificed and the left kidney was excised for calculation of kidney hypertrophy index (KHI), observation of renal pathological changes using light microscope and electron microscope. Mean glomerular cross-sectional areas (MGA), mean glomerular volume (MGV), glomerular basement membrane thickness and foot process fusion ratio were calculated. RT-PCR was employed for detection of podocalyxin (PCX) protein expression. RESULTS: Results showed that levels of hemoglobin A1c, BUN, SCr in Groups B, C, D and E rats were significantly higher than those in Group A (P<0.05), while BUN and SCr levels in rats of Groups C, D and E were significantly lower than those in Group B (P<0.05). KHI, MGA and MGV levels were significantly higher in Groups B, C, D and E rats than those in Group A (P<0.05); KHI and MGA levels in Group B rats were significantly higher than those in Groups C, D and E (P<0.05) and MGV in Groups D and E was significantly lower than that in Groups B and C (P<0.05). Histology study showed normal glomerulus structure, morphology, volume, endothelial cells and mesangial cells as well as clear glomerular capillary in Group A rats. Renal mesangial matrix proliferation and expansion of glomerulus cavities in Groups B, C, D and E were observed. However, damage degree in Groups C, D and E were more moderate than that in Group B. CONCLUSIONS: Pioglitazone can reduce kidney damage in diabetic rats, which may be attributed to its role in increasing glomerular PCX protein expression and inhibiting urinary excretion of PCX, and its effect is dose dependent. PMID- 25129468 TI - Role of immune dysfunction in pathogenesis of type 1 diabetes mellitus in children. AB - OBJECTIVES: To investigate the function of cytokines, chemokines, and regulatory T cells (Tregs) in the pathogenesis of type 1 diabetes mellitus (T1DM) in children. METHODS: A total of 35 children with T1DM and 30 healthy controls were enrolled in this study. Levels of serum cytokines (IL-1alpha, IL-6, IL-10, IL-12, and TNF-alpha) and chemokines (MIP-1alpha, MIP-1alpha and MCP-1) were detected by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) were isolated and culture supernatant of phytohaemagglutinin (PHA)-stimulated PBMCs was subjected to ELISA for levels of cytokines (IL-1alpha, IL-6, IL-10, IL 12 and TNF-alpha) in T1DM and control group. Furthermore, flow cytometry was used to determine the percentage of Tregs in PBMCs of two groups. RESULTS: Levels of serum cytokines including IL-1alpha, IL-6, IL-10 and TNF-alpha as well as chemokines, such as MIP-1alpha and MIP-1alpha in children with T1DM children were significantly higher than those in healthy controls (P<0.05, respectively). PBMCs with PHA stimulation in T1DM group secreted more IL-1alpha and TNF-alpha (P<0.05, respectively), but less IL-10 (P<0.05), as compared with control group. Furthermore, the proportion of CD4(+), CD25(+), Foxp3(+), Tregs in PBMCs isolated from children with T1DM was obviously lower than those in healthy controls (P<0.05). CONCLUSIONS: Immune dysfunction, with upregulation of inflammatory factors such as IL-1alpha, IL-6, TNF-alpha and MIP-1alpha, downregulation of IL 10 and Tregs, plays an important role in the pathogenesis of T1DM in children. PMID- 25129469 TI - Role of NLRP3 and NLRP1 inflammasomes signaling pathways in pathogenesis of rheumatoid arthritis. AB - OBJECTIVES: To investigate the role of NLRP3 and NLRP1 inflammasomes signaling pathways in rheumatoid arthritis (RA). METHODS: A total of 36 patients with RA were selected, peripheral blood mononuclear cell (PBMC) and granulocyte were separated from venous blood. RT-qPCR method was used to detect the expression level and diversity of NLRP3 and NLRP1 in PBMC and granulocyte mRNA in patients with RA, and detect the mRNA expression of downstream factor IL-1alpha. The correlation between RA and the expression of NLRP3 and NLRP1 was analyzed. Normal 30 cases were set as control group. RESULTS: Expression levels of NLRP1, and caspase-1 mRNA in PBMC of RA group were significantly lower than those of control group (P<0.05), while there was no significant difference in expression levels of NLRP3, ASC, IL-1alpha mRNA between these two groups (P>0.05); NLRP3, caspase-1, and ASC mRNA expression in granulocyte of RA patients were significantly lower than those in control group (P<0.05). There was no correlation between rheumatoid factor and expression levels of NLRP3, ASC, caspase-1 mRNA in RA group (P>0.05); NLRP1, IL-1alpha mRNA expression level had a negative correlation with anti rheumatoid factor antibody (P=0.033 2, 0.034 0). CONCLUSIONS: NLRP3 and NLRP1 inflammasomes signaling pathways are involved in RA inflammatory reaction process as protective factors, and play an important role in RA inflammatory mechanisms. PMID- 25129470 TI - Conserved regions of Plasmodium vivax potential vaccine candidate antigens in Sri Lanka: conscious in silico analysis of prospective conformational epitope regions. AB - OBJECTIVES: To do mapping and modeling of conformational B cell epitope regions of highly conserved and protective regions of three merozoitecandidate vaccine proteins of Plasmodium vivax (P. vivax), ie. merozoite purface protein-1 (PvMSP 1), apical membrane antigen -1 domain ? (PvAMA1-D?) and region ? of the Duffy binding protein (PvDBP?), and to analyze the immunogenic properties of these predicted epitopes. METHODS: 3-D structures of amino acid haplotypes from Sri Lanka (available in GeneBank) of PvMSP-119 (n=27), PvAMA1-D? (n=21) and PvDBP? (n=33) were modeled. SEPPA, selected as the best online server was used for conformational epitope predictions, while prediction and modeling of protein structure and properties related to immunogenicity was carried out with Geno3D server, SCRATCH Protein Server, NetSurfP Server and standalonesoftware, Genious 5.4.4. RESULTS: SEPPA revealed that regions of predicted conformational epitopes formed 4 clusters in PvMSP-I19, and 3 clusters each in PvAMA1-D? and PvDBP?, all of which displayed a high degree of hydrophilicity, contained solvent exposed residues, displayed high probability of antigenicity and showed positive antigenic propensity values, that indicated high degree of immunogenicity. CONCLUSIONS: Findings of this study revealed and confirmed that different parts of the sequences of each of the conserved regions of the three selected potential vaccine candidate antigens of P. vivax are important with regard to conformational epitope prediction that warrants further laboratory experimental investigations in in vivo animal models. PMID- 25129471 TI - Identification and characterization of TCRgamma and TCRdelta chains in channel catfish, Ictalurus punctatus. AB - Channel catfish, Ictalurus punctatus, T cell receptors (TCR) gamma and delta were identified by mining of expressed sequence tag databases, and full-length sequences were obtained by 5'-RACE and RT-PCR protocols. cDNAs for each of these TCR chains encode typical variable (V), diversity (D), joining (J), and constant (C) regions. Three TCRgamma V families, seven TCRgamma J sequences, and three TCRgamma C sequences were identified from sequencing of cDNA. Primer walking on bacterial artificial chromosomes (BACs) confirmed that the TRG locus contained seven TRGJ segments and indicated that the locus consists of (Vgamma3-Jgamma6 Cgamma2)-(Vgamma1n-Jgamma7-Cgamma3)-(Vgamma2-Jgamma5-Jgamma4-Jgamma3-Jgamma2 Jgamma1-Cgamma1). In comparison for TCRdelta, two V families, four TCRdelta D sequences, one TCRdelta J sequence, and one TCRdelta C sequence were identified by cDNA sequencing. Importantly, the finding that some catfish TCRdelta cDNAs contain TCR Valpha-D-Jdelta rearrangements and some TCRalpha cDNAs contain Vdelta Jalpha rearrangements strongly implies that the catfish TRA and TRD loci are linked. Finally, primer walking on BACs and Southern blotting suggest that catfish have four TRDD gene segments and a single TRDJ and TRDC gene. As in most vertebrates, all three reading frames of each of the catfish TRDD segments can be used in functional rearrangements, and more than one TRDD segment can be used in a single rearrangement. As expected, catfish TCRdelta CDR3 regions are longer and more diverse than TCRgamma CDR3 regions, and as a group they utilize more nucleotide additions and contain more nucleotide deletions than catfish TCRgamma rearrangements. PMID- 25129472 TI - Survey of major histocompatibility complex class II diversity in pig-tailed macaques. AB - Pig-tailed macaques (Macaca nemestrina) serve as important models for human infectious disease research. Major histocompatibility complex (MHC) class II molecules are important to this research since they present peptides to CD4+ T cells. Despite the importance of characterizing the MHC-II alleles expressed in model species like pig-tailed macaques, to date, less than 150 MHC-II alleles have been named for the six most common classical class II loci (DRA, DRB, DQA, DQB, DPA, and DPB) in this population. Additionally, only a small percentage of these alleles are full-length, making it impossible to use the known sequence for reagent development. To address this, we developed a fast, high-throughput method to discover full-length MHC-II alleles and used it to characterize alleles in 32 pig-tailed macaques. By this method, we identified 128 total alleles across all six loci. We also performed an exon 2-based genotyping assay to validate the full length sequencing results; this genotyping assay could be optimized for use in determining MHC-II allele frequencies in large cohorts of pig-tailed macaques. PMID- 25129473 TI - Pericardial effusion following transcatheter aortic valve implantation: echocardiography and multi-detector row computed tomography evaluation. AB - Although pericardial effusion (PE) early after transcatheter aortic valve implantation (TAVI) has been reported in few registries, late PE at follow-up remains unexplored. Particularly, after transapical TAVI, diagnosis of PE with transthoracic echocardiography (TTE) may be challenging. The present evaluation assessed the incidence of PE early after TAVI and at 1 month follow-up using TTE and multi-detector computed tomography (MDCT). The agreement between TTE and MDCT to diagnose the presence and severity of PE at 1 month follow-up was evaluated. Overall 293 patients undergoing TAVI were included. Pre-discharge TTE was performed in all patients. At 1 month, repeat TTE was performed in 234 patients and additional MDCT evaluation in 143 patients. Pre-discharge small and moderate PE was observed in 74.1 and 4.1 % of patients, respectively, whereas significant PE was diagnosed in 8 (2.7 %) patients without differences between procedural access: 1.6 versus 3.6 % for transfemoral and transapical respectively, p = 0.474. At 1 month new-onset moderate PE was noted in 6 (2.5 %) patients all of who underwent transapical TAVI. MDCT and TTE disagreed on the grade of PE in 38 patients. Importantly, one patient with small PE on TTE was considered having moderate PE and two patients with small and moderate PE were considered having large PE. Also, two patients with moderate PE on echocardiography were considered small PE on MDCT. In conclusions, significant PE early after TAVI is infrequent. The prevalence of small and moderate PE remains stable at 1 month follow-up. MDCT refines the diagnosis of significant PE. PMID- 25129476 TI - A light initiated chemiluminescent immunoassay for procalcitonin. PMID- 25129474 TI - Associated factors with antipsychotic use in long-term institutional care in eight European countries: Results from the RightTimePlaceCare study. AB - OBJECTIVES: To determine factors associated with the antipsychotic (AP) prescription for people with dementia (PwD) recently admitted to institutional long-term care facilities (LTCFs) and to ascertain differences in the use of this medication in 8 European countries. DESIGN: An exploratory cross-sectional study. SETTING: LTCFs from 8 European countries (Estonia, Finland, France, Germany, The Netherlands, Spain, Sweden, and England). PARTICIPANTS: A total of 791 PwD recently admitted to an LTCF and their caregivers. MEASUREMENTS: Baseline data from RightTimePlaceCare survey was used. Patients' medical conditions, neuropsychiatric symptoms, physical and cognitive status, and medications were recorded. Multiple logistic regression models were used to assess associations with the AP use. RESULTS: A group of 296 patients (37.4%) of 791 patients recently admitted received AP medication. The prevalence of the use of 1 or more APs varied between study countries, ranging from 12% in Sweden to 54% in Spain. Factors independently associated with the AP use were living in Sweden [odds ratio (OR) 0.12, 95% confidence interval (CI) 0.05-0.30], Finland (OR 0.26, 95% CI 0.14-0.48), Germany (OR 2.75, 95% CI 1.55-4.86) and Estonia (OR 6.79, 95% CI 3.84-12.0). The odds of AP use decreased with the presence of a dementia specific unit in the LTCF (OR 0.60, 95% CI 0.39-0.92), but was higher among residents with a hyperactivity behavior (OR 2.12, 95% CI 1.41-3.18). CONCLUSION: The current study shows that more than one-third of the residents recently admitted received APs and that prescription frequency across countries varied significantly. This study raises the possibility that the presence of a dementia-specific unit might play a role in the AP use. Further studies should investigate this association and seek better understanding of what will achieve optimal quality of AP use among newly admitted residents in LTCF. PMID- 25129475 TI - Perioperative changes in pro and anticoagulant factors in prostate cancer patients undergoing laparoscopic and robotic radical prostatectomy with different anaesthetic techniques. AB - BACKGROUND: Laparoscopic prostatectomy (LRP) may activate clotting system influencing the risk of perioperative thrombosis in patients with prostate cancer. Moreover, different anaesthetic techniques can also modify coagulant factors. Thus, the aim of this study was to investigate the effects on pro- and anti-coagulant and fibrinolytic factors of two established types of anaesthesia in patients with prostate cancer undergoing elective LRP. METHODS: 102 patients with primary prostate cancer, who underwent conventional LRP or robot-assisted laparoscopic prostatectomy (RALP), were studied and divided into 2 groups to receive total intravenous anesthesia with target-controlled infusion (TIVA-TCI) or balanced inhalation anaesthesia (BAL) prior to surgery. Before the induction of anaesthesia (T0), 1 hr (T1) and 24 hrs post-surgery (T2), some pro-coagulant factors, fibronolysis markers, p-selectin and haemostatic system inhibitors were evaluated. RESULTS: Both TIVA-TCI and BAL patients showed a marked and significant increase in pro-coagulant factors and consequent reduction in haemostatic system inhibitors in the early post operative period (p <= 0.004 for each markers). Use of RALP showed a significant increase in prothrombotic markers as compared to LRP. In TIVA patients undergoing LRP, a significant reduction of p selectin levels between T0 and T2 (p = 0.001) was observed as compared to BAL, suggesting a better protective effect on platelet activation of anaesthetic agents used for TIVA. CONCLUSIONS: Both anaesthetic techniques significantly seem to increase the risk of thrombosis in prostate cancer patients undergoing LRP, mainly when the robotic device was utilized, encouraging the use of a peri operative thromboembolic prophylaxis in these patients. PMID- 25129477 TI - Role of Fas/FasL signaling in regulation of anti-viral response during HSV-2 vaginal infection in mice. AB - Fas receptor-Fas ligand (FasL) signaling is involved in apoptosis of virus infected cells but increasing evidence accumulates on Fas receptor as a mediator of apoptosis-independent processes such as induction of activating and pro inflammatory signals. In this study, we examined the role of Fas/FasL pathway in regulation of anti-viral response to genital HSV-2 infection using a murine model of HSV-2 infection applied to C57BL6/J, B6. MRL-Faslpr/J and B6Smn.C3-Faslgld/J mice. HSV-2 infection of Fas- and FasL-deficient mice led to decreased migration of IFN-gamma expressing NK cells and CD4+ T cells, but not of gammadelta T cells, into the vaginal tissue. The vaginal tissues of HSV-2 infected Fas- and FasL deficient mice showed increased production of IL-10, followed by low expression of the early CD69 activation marker on CD4+ and CD8+ T cells and increased numbers of regulatory T cells (Tregs). Experiments in co-cultures of CD4+ T cells and bone marrow derived dendritic cells showed that lack of bilateral Fas-FasL signaling led to expansion of Tregs and increased production of IL-10 and TGF beta1. Our results demonstrate that Fas/FasL can regulate development of tolerogenic dendritic cells and expansion of Tregs early during HSV-2 infection, which further influences effective anti-viral response. PMID- 25129478 TI - Modulatory role of vitamin A on the Candida albicans-induced immune response in human monocytes. AB - Beyond its well-documented role in reproduction, embryogenesis and maintenance of body tissues, vitamin A has attracted considerable attention due to its immunomodulatory effects on both the innate and the adaptive immune responses. In infectious diseases, vitamin A has been shown to have a host-protective effect in infections of bacterial, viral or protozoan origin. Nevertheless, its impact in fungal infections remains unknown. Meanwhile, the frequency of invasive mycoses keeps on growing, with Candida albicans being the major opportunistic fungal pathogen and associated with high mortality. In the present work, we explored the impact of all-trans retinoic acid (atRA), the most active metabolite of vitamin A, on the innate immune response against C. albicans in human monocytes. Our results show a strong immunomodulatory role for atRA, leading to a significant down-regulation of the fungi-induced expression and secretion of the pro inflammatory cytokines TNFalpha, IL6 and IL12. Moreover, atRA significantly suppressed the expression of Dectin-1, a major fungal pattern recognition receptor, as well as the Dectin-1-dependent cytokine production. Both RAR dependent and RAR-independent mechanisms seem to play a role in the atRA-mediated immunomodulation. Our findings open a new direction to elucidate the role of vitamin A on the immune function during fungal infections. PMID- 25129479 TI - CAPON-nNOS coupling can serve as a target for developing new anxiolytics. AB - Anxiety disorders are highly prevalent psychiatric diseases. There is need for a deeper understanding of anxiety control mechanisms in the mammalian brain and for development of new anxiolytic agents. Here we report that the coupling between neuronal nitric oxide synthase (nNOS) and its carboxy-terminal PDZ ligand (CAPON) can serve as a target for developing new anxiolytic agents. Augmenting nNOS-CAPON interaction in the hippocampus of mice by overexpressing full-length CAPON gave rise to anxiogenic-like behaviors, whereas dissociating CAPON from nNOS by overexpressing CAPON-125C or CAPON-20C (the C-terminal 125 or 20 amino acids of CAPON) or delivering Tat-CAPON-12C (a peptide comprising Tat and the 12 C terminal amino acids of CAPON) in the hippocampus of mice produced anxiolytic like effects. Mice subjected to chronic mild stress (CMS) displayed a substantial increase in nNOS-CAPON coupling in the hippocampus and a consequent anxiogenic like phenotype. Disrupting nNOS-CAPON coupling reversed the CMS-induced anxiogenic-like behaviors. Moreover, small-molecule blockers of nNOS-CAPON binding rapidly produced anxiolytic-like effects. Dexamethasone-induced ras protein 1 (Dexras1)-extracellular signal-regulated kinase (ERK) signaling was involved in the behavioral effects of nNOS-CAPON association. Thus, nNOS-CAPON association contributes to the modulation of anxiety-related behaviors via regulating Dexras1-ERK signaling and can serve as a target for developing potential anxiolytics. PMID- 25129480 TI - In vivo proteomic imaging analysis of caveolae reveals pumping system to penetrate solid tumors. AB - Technologies are needed to map and image biological barriers in vivo that limit solid tumor delivery and, ultimately, the effectiveness of imaging and therapeutic agents. Here we integrate proteomic and imaging analyses of caveolae at the blood-tumor interface to discover an active transendothelial portal to infiltrate tumors. A post-translationally modified form of annexin A1 (AnnA1) is selectively concentrated in human and rodent tumor caveolae. To follow trafficking, we generated a specific AnnA1 antibody that targets caveolae in the tumor endothelium. Intravital microscopy of caveolae-immunotargeted fluorophores even at low intravenous doses showed rapid and robust pumping across the endothelium to enter mammary, prostate and lung tumors. Within 1 h, the fluorescence signal concentrated throughout tumors to exceed the peak levels in blood. This transvascular pumping required the expression of caveolin 1 and annexin A1. Tumor uptake with other antibodies were >100-fold less. This proteomic imaging strategy reveals a unique target, antibody and caveolae pumping system for solid tumor penetration. PMID- 25129482 TI - IGRA as a predictive factor of silent pulmonary changes in individuals following exposure to tuberculosis. AB - OBJECTIVES: We conducted a study on usefulness of the tuberculin skin test (TST) and the Quantiferon-TB Gold IT (QFT) tests as predictors of radiological changes after contact with tuberculosis. MATERIALS AND METHODS: The study group consisted of TB-exposed HCWs working in the Military Institute of Medicine (Warsaw, Poland). The usefulness of TST, QFT, and a combination of both tests was assessed for prediction of silent radiological findings. RESULTS: 83 previously TB-exposed participants were recruited. None of the participants had a history of active tuberculosis. Positive TST results were reported in 72 (86.8 %) participants, and positive QFTs were observed in 27 (32.5 %) cases. Chest radiographs revealed 23 findings specific for non-active tuberculosis in 18 (21.7 %) participants. The results of the QFTs were associated with the highest negative predictive value, positive predictive value, and positive likelihood ratio of silent chest X-ray findings suggestive of latent tuberculosis infection. Positive QFT was the only statistically significant variable that increases the odds ratio (OR-8.3) of the presence of typical of tuberculosis radiological changes in the lung. CONCLUSION: A positive QFT result in an individual with no TB history who was exposed to tuberculosis in the past is associated with a significantly higher risk of clinically silent parenchymal lesions in lungs suggestive of previous tuberculosis. PMID- 25129481 TI - Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. AB - Alopecia areata (AA) is a common autoimmune disease resulting from damage of the hair follicle by T cells. The immune pathways required for autoreactive T cell activation in AA are not defined limiting clinical development of rational targeted therapies. Genome-wide association studies (GWAS) implicated ligands for the NKG2D receptor (product of the KLRK1 gene) in disease pathogenesis. Here, we show that cytotoxic CD8(+)NKG2D(+) T cells are both necessary and sufficient for the induction of AA in mouse models of disease. Global transcriptional profiling of mouse and human AA skin revealed gene expression signatures indicative of cytotoxic T cell infiltration, an interferon-gamma (IFN-gamma) response and upregulation of several gamma-chain (gammac) cytokines known to promote the activation and survival of IFN-gamma-producing CD8(+)NKG2D(+) effector T cells. Therapeutically, antibody-mediated blockade of IFN-gamma, interleukin-2 (IL-2) or interleukin-15 receptor beta (IL-15Rbeta) prevented disease development, reducing the accumulation of CD8(+)NKG2D(+) T cells in the skin and the dermal IFN response in a mouse model of AA. Systemically administered pharmacological inhibitors of Janus kinase (JAK) family protein tyrosine kinases, downstream effectors of the IFN-gamma and gammac cytokine receptors, eliminated the IFN signature and prevented the development of AA, while topical administration promoted hair regrowth and reversed established disease. Notably, three patients treated with oral ruxolitinib, an inhibitor of JAK1 and JAK2, achieved near complete hair regrowth within 5 months of treatment, suggesting the potential clinical utility of JAK inhibition in human AA. PMID- 25129483 TI - A QM/MM study of the associative mechanism for the phosphorylation reaction catalyzed by protein kinase A and its D166A mutant. AB - Here we analyze in detail the possible catalytic role of the associative mechanism in the gamma-phosphoryl transfer reaction in the catalytic subunit of the mammalian cyclic AMP-dependent protein kinase (PKA) enzyme and its D166A mutant. We have used a complete solvated model of the ATP-Mg2-Kemptide/PKA system and good levels of theory (B3LYP/MM and MP2/MM) to determine several potential energy paths from different MD snapshots, and we present a deep analysis of the interaction distances and energies between ligands, metals and enzyme residues. We have also tested the electrostatic stabilization of the transition state structures localized herein with the charge balance hypothesis. Overall, the results obtained in this work reopen the discussion about the plausibility of the associative reaction pathway and highlight the proposed role of the catalytic triad Asp166-Lys168-Thr201. PMID- 25129484 TI - Exploring the dynamics and interaction of a full ErbB2 receptor and Trastuzumab Fab antibody in a lipid bilayer model using Martini coarse-grained force field. AB - Coarse grained (CG) modeling has been applied to study the influence of the Trastuzumab monoclonal antibody on the structure and dynamics of the full ErbB2 receptor dimer, including the lipid bilayer. The usage of CG models to study such complexes is almost mandatory, at present, due to the large size of the whole system. We will show that the Martini model performs satisfactorily well, giving results well-matched with those obtained by atomistic models as well as with the experimental information existing on homolog receptors. For example, the extra and intracellular domains approach the bilayer surface in both the monomer and dimer cases. The Trastuzumab-Fab hinders the interaction of the receptors with the lipid bilayer. Another interesting effect of the antibody is the disruption of the antiparallel arrangement of the juxtamembrane segments in the dimer case. These findings might help to understand the effect of the antibody on the receptor bioactivity. PMID- 25129485 TI - Buttressing the staple line: a randomized comparison between staple-line reinforcement versus no reinforcement during sleeve gastrectomy. AB - Bariatric surgery is recommended for Indian patients with body mass index (BMI) >32.5 kg/m(2) with at least one comorbidity and >37.5 kg/m(2) without a comorbidity. In laparoscopic sleeve gastrectomy, bleeding and leakage from the staple line are common post-operative events. Peri-Strips Dry(r) with Veritas(r) (PSD-V) is used in staple-line reinforcement. This was a single-investigator, multicenter, randomized study of 100 patients undergoing standard sleeve gastrectomy with a 34 or 36 French bougie. Patients were randomized 1:1 to PSD-V or control groups; no buttress material was used in the control group. The primary objective was to assess complication rates (any staple-line bleed or leak from the intra-operative visit through day 30) associated with sleeve gastrectomy. Surgical time (from first incision to closure of last incision) and the number of clips and/or sutures used to control bleeding were also assessed. Fewer staple-line bleeds were observed in the PSD-V group than the control group (23/51 [45.1 %] vs 39/49 [79.6 %] patients; p=0.0005), and the bleeding was of a lower severity (p=0.0002). No staple-line leaks were observed. Surgical time was shorter in patients who received PSD-V (58.8 vs 72.8 min; p=0.0153), and fewer patients required hemostatic clips and/or sutures (10/51 [19.6 %] vs 33/49 [67.3 %] patients; p<0.0001). Fewer patients in the PSD-V than the control group experienced adverse events (2/51 [3.9 %] vs 5/49 [10.2 %] patients). The use of PSD-V reduced the incidence and severity of staple-line bleeding and was associated with a reduction in surgical time compared with no staple-line reinforcement. PMID- 25129486 TI - An update on United States asthma centers: 2013. PMID- 25129487 TI - Prevalence and determinants of atopy and allergic diseases among school-age children in rural Saskatchewan, Canada. AB - BACKGROUND: There have been few investigations of farming-related activities or specific characteristics resulting in the associations between those exposures and atopic disease. OBJECTIVE: To study the associations between farm-associated exposures and atopic diseases. METHODS: As part of a longitudinal study of lung health in rural residents, a cross-sectional baseline study was conducted in rural Saskatchewan, Canada. This included an initial survey phase followed by a clinical testing phase. A subsample of 584 children (grades 1-8) completed skin prick testing to assess atopic status. Atopy was defined as a positive reaction to any of 6 allergens (local grasses, wheat dust, cat dander, house dust mite, Alternaria species, or Cladosporium species) of at least 3 mm compared with the negative control. RESULTS: Of those who completed clinical testing, the prevalence of atopy was 19.4%, that of hay fever was 8.8%, and that of eczema was 27.4%. Based on skin prick testing, sensitization was highest for cat dander (8.6%) followed by local grasses (8.2%) and house dust mite (5.1%). After adjustment for potential confounders, home location (farm vs non-farm) was not associated with atopic status. However, livestock farming was protective against atopy (adjusted odds ratio 0.38, 95% confidence interval 0.17-0.88). In contrast, current residence on a farm was associated with an increase in the likelihood of hay fever in these children (adjusted odds ratio 3.68, 95% confidence interval 1.29-10.45). Also, regular farming activities in the past year were associated with an increased risk of hay fever. CONCLUSION: In children, livestock exposure has a protective effect on skin prick test positivity, whereas farm living and activities increase the risk of hay fever. PMID- 25129488 TI - Exploring the link between ceramide and ionizing radiation. AB - The aim of radiotherapy is to eradicate cancer cells with ionizing radiation; tumor cell death following irradiation can be induced by several signaling pathways, most of which are triggered as a consequence of DNA damage, the primary and major relevant cell response to radiation. Several lines of evidence demonstrated that ceramide, a crucial sensor and/or effector of different signalling pathways promoting cell cycle arrest, death and differentiation, is directly involved in the molecular mechanisms underlying cellular response to irradiation. Most of the studies strongly support a direct relationship between ceramide accumulation and radiation-induced cell death, mainly apoptosis; for this reason, defining the contribution of the multiple metabolic pathways leading to ceramide formation and the causes of its dysregulated metabolism represent the main goal in order to elucidate the ceramide-mediated signaling in radiotherapy. In this review, we summarize the current knowledge concerning the different routes leading to ceramide accumulation in radiation-induced cell response with particular regard to the role of the enzymes involved in both ceramide neogenesis and catabolism. Emphasis is placed on sphingolipid breakdown as mechanism of ceramide generation activated following cell irradiation; the functional relevance of this pathway, and the role of glycosphingolipid glycohydrolases as direct targets of ionizing radiation are also discussed. These new findings add a further attractive point of investigation to better define the complex interplay between sphingolipid metabolism and radiation therapy. PMID- 25129489 TI - Long term survival in a case of concurrent retroperitoneal liposarcoma and renal cell carcinoma: a case report. AB - BACKGROUND: Liposarcoma is one of the most common soft tissue sarcomas found in adults. It has a predilection for retroperitoneal space. Renal cell carcinoma is the most common tumor of the kidney. CASE PRESENTATION: Concurrent retroperitoneal liposarcoma and renal cell carcinoma were found in a 34-year-old Japanese man. The renal tumor was first detected by ultrasonography, it was confirmed by computed tomography, which also identified a presumptive retroperitoneal liposarcoma, and the tumors were further assessed with magnetic resonance imaging. The patient was treated by surgical resection of retroperitoneal liposarcoma and left nephrectomy and has been disease-free for 10 years. CONCLUSIONS: The concomitant occurrence of a renal tumor and a primary primary liposarcoma is rare. The major factors promoting a good prognosis in this case were the favorable histology and the small size of the tumors. PMID- 25129491 TI - A pilot study of S-1-based concurrent chemoradiotherapy in patients with biliary tract cancer. AB - PURPOSE: S-1 chemotherapy is effective against advanced biliary tract cancer. The purpose was to evaluate the efficacy and safety of S-1-based concurrent chemoradiotherapy in patients with advanced biliary tract cancer. METHODS: Patients with pathologically-proven advanced biliary tract cancer were eligible. S-1 was orally administered at a dose of 40 mg/m(2), twice daily from day 1 to 14 and from day 22 to 35; concurrent radiotherapy of 180-200 cGy per fraction was delivered in 25-28 fractions. After treatment completion, tumor response was evaluated by computed tomography. In the first stage of the optimal two-stage phase II design, 18 patients were required. RESULTS: Twenty patients were enrolled between August 2006 and February 2009. The median age was 62.5 years (range 45-77 years). The median follow-up time was 11.6 months (range 1.9-49.1 months). Fifteen patients (75%) had extrahepatic cholangiocarcinoma, two patients (10%) had intrahepatic cholangiocarcinoma, and three patients (15%) had gallbladder cancer. After treatment, a partial response was achieved in three patients (15%), and stable disease was achieved in 14 patients (70%). The overall response rate was 15%, and the disease stabilization rate was 85%. There was no grade 4 toxicity or treatment-related death. The common grade 3 toxicities were thrombocytopenia (15%), neutropenia (10%), and nausea (10%). The median progression-free survival and median overall survival were 5.9 months (range 2.2 9.5 months) and 10.8 months (range 1.1-20.4 months), respectively. CONCLUSIONS: This study shows that S-1-based concurrent chemoradiotherapy is feasible and tolerable in patients with advanced biliary tract cancer. It will be further confirmed in a following large-scale phase II study. PMID- 25129492 TI - Utilization of roughages and concentrates relative to that of milk replacer increases strongly with age in veal calves. AB - We aimed to investigate the feeding values of milk replacer (MR), roughage, and concentrates for veal calves in a paired-gain setting, thus avoiding any prior assumptions in feeding values and major differences in nutrient intakes. One hundred sixty male Holstein-Friesian calves at 2 wk of age and 45 +/- 0.2 kg of body weight (BW) were included in the experiment. Calves were allocated to pens (5 calves per pen) and pens were randomly assigned to 1 of 4 solid feed (SF) levels: SF1, SF2, SF3, or SF4, respectively, and to 1 of 2 roughage-to concentrate (R:C) ratios: 20:80 or 50:50. An adaptation period from wk 1 to 10 preceded the experimental period (wk 11 to 27). Total dry matter (DM) intake from SF was targeted to reach 20, 100, 180, and 260 kg of DM for SF1 to SF4, respectively, during the 16-wk experimental period, and increased with preplanned, equal weekly increments. Roughage was composed of 50% corn silage and 50% chopped wheat straw based on DM. The quantity of MR provided was adjusted every 2 wk based on BW to achieve similar targeted rates of carcass gain across treatments. The reduction in MR provided (in kg of DM) to realize equal rates of carcass gain with inclusion of SF (in kg of DM) differed between the R:C ratio of 50:50 (0.41 kg of MR/kg of SF) and the R:C ratio of 20:80 (0.52 kg of MR/kg of SF). As carcass gain unintentionally increased with SF intake, the paired-gain objective was not fully achieved. When adjusted for realized rates of carcass gain, calves fed an R:C ratio of 20:80 still required 10% less MR than calves fed an R:C ratio of 50:50 for equal rates of carcass gain, indicating that the utilization of SF for gain increased with concentrate inclusion. Averaged for the 16-wk experimental period, the feeding value of MR relative to that of concentrates and roughages was close to that predicted based on their respective digestible energy contents. Nevertheless, the feeding value of SF relative to that of MR increased substantially with age. Therefore, additivity in feeding values of these ration components cannot be assumed. The results of the current study may contribute to the development of new concepts for formulation of veal calf diets with substantial amounts of SF. PMID- 25129493 TI - Short communication: Added value of rumination time for the prediction of dry matter intake in lactating dairy cows. AB - The objective of the current study was to quantify the change in the prediction of dry matter intake (DMI) resulting from the inclusion of rumination time (RT) in the 2001 National Research Council (NRC) DMI prediction model. Forty-one Holstein cows fed the same total mixed ration were involved in a 10-wk study. Individual DMI were measured daily. The accuracy and precision of the original NRC prediction model, based on body weight, fat-corrected milk, and week of lactation as independent variables, was compared with the accuracy and precision of the same model with RT as an additional independent variable. The RT estimate was significant in the model developed but had a low value (0.031 kg/h). Root mean square prediction errors were very similar in the 2 models (1.70 and 1.68 kg/d) as were the other indicators (R(2), linear bias, random error, and concordance correlation coefficient) selected to compare the models in this study. These results indicate no gain in DMI prediction precision or accuracy when RT is included in the NRC model. PMID- 25129494 TI - Factors affecting life cycle assessment of milk produced on 6 Mediterranean buffalo farms. AB - This study quantifies the environmental impact of milk production of Italian Mediterranean buffaloes and points out the farm characteristics that mainly affect their environmental performance. Life cycle assessment was applied in a sample of 6 farms. The functional unit was 1 kg of normalized buffalo milk (LBN), with a reference milk fat and protein content of 8.3 and 4.73%, respectively. The system boundaries included the agricultural phase of the buffalo milk chain from cradle to farm gate. An economic criterion was adopted to allocate the impacts on milk production. Impact categories investigated were global warming (GW), abiotic depletion (AD), photochemical ozone formation (PO), acidification (AC), and eutrophication (EU). The contribution to the total results of the following farm activities were investigated: (1) on-farm energy consumption, (2) manure management, (3) manure application, (4) on-farm feed production (comprising production and application of chemical fertilizers and pesticides), (5) purchased feed production, (6) enteric fermentation, and (7) transport of purchased feeds, chemical fertilizers, and pesticides from producers to farms. Global warming associated with 1 kg of LBN resulted in 5.07 kg of CO2 Eq [coefficient of variation (CV)=21.9%], AD was 3.5 * 10(-3) kg of Sb Eq (CV=51.7%), PO was 6.8 * 10(-4) kg of C2H4 Eq (CV=28.8%), AC was 6.5 * 10(-2) kg of SO2 Eq (CV=30.3%), and EU was 3.3 * 10(-2) kg of PO4(3-) Eq (CV=36.5%). The contribution of enteric fermentation and manure application to GW is 37 and 20%, respectively; on-farm consumption, on-farm feed production, and purchased feed production are the main contributors to AD; about 70% of PO is due to enteric fermentation; manure management and manure application are responsible for 55 and 25% of AC and 25 and 55% of EU, respectively. Methane and N2O are responsible for 44 and 43% of GW, respectively. Crude oil consumption is responsible for about 72% of AD; contribution of CH4 to PO is 77%; NH3 is the main contributor to AC (92%); NO3(-) and NH3 are responsible for 55 and 41% of EU, respectively; contribution of P to EU is only 3.2%. The main characteristics explaining the significant variability of life cycle assessment are milk productivity and amount of purchased feed per kilogram of LBN. Improvement of LBN production per buffalo cow is the main strategy for reducing GW and PO; improvement of the efficiency of feed use is the strategy proposed for mitigating AD, PO, AC, and EU. PMID- 25129490 TI - Biological Modulators in Eosinophilic Diseases. AB - Eosinophils can regulate local and systemic inflammation, and their presence in higher numbers appears to play an important role in the pathology of various atopic and inflammatory diseases. Eosinophil maturation, recruitment, and survival depend on several cytokine regulators, including interleukin (IL)-5, IL 4, and IL-13 as well as growth factors such as GM-CSF. Over the last decade, the approach to treating eosinophilic diseases has changed greatly. A number of biologic modulators have been developed to target eosinophilic inflammatory pathways, and their usage has resulted in variable clinical improvement in the treatment of eosinophilic-associated conditions. Novel targeted therapies that are safe and effective for treating these disorders are being investigated. This review summarizes the clinical use of biologic agents that have been studied in clinical trials or approved for treating eosinophilic diseases. PMID- 25129495 TI - Comparison of genomic predictions using genomic relationship matrices built with different weighting factors to account for locus-specific variances. AB - Various models have been used for genomic prediction. Bayesian variable selection models often predict more accurate genomic breeding values than genomic BLUP (GBLUP), but GBLUP is generally preferred for routine genomic evaluations because of low computational demand. The objective of this study was to achieve the benefits of both models using results from Bayesian models and genome-wide association studies as weights on single nucleotide polymorphism (SNP) markers when constructing the genomic matrix (G-matrix) for genomic prediction. The data comprised 5,221 progeny-tested bulls from the Nordic Holstein population. The animals were genotyped using the Illumina Bovine SNP50 BeadChip (Illumina Inc., San Diego, CA). Weighting factors in this investigation were the posterior SNP variance, the square of the posterior SNP effect, and the corresponding minus base-10 logarithm of the marker association P-value [-log10(P)] of a t-test obtained from the analysis using a Bayesian mixture model with 4 normal distributions, the square of the estimated SNP effect, and the corresponding log10(P) of a t-test obtained from the analysis using a classical genome-wide association study model (linear regression model). The weights were derived from the analysis based on data sets that were 0, 1, 3, or 5 yr before performing genomic prediction. In building a G-matrix, the weights were assigned either to each marker (single-marker weighting) or to each group of approximately 5 to 150 markers (group-marker weighting). The analysis was carried out for milk yield, fat yield, protein yield, fertility, and mastitis. Deregressed proofs (DRP) were used as response variables to predict genomic estimated breeding values (GEBV). Averaging over the 5 traits, the Bayesian model led to 2.0% higher reliability of GEBV than the GBLUP model with an original unweighted G-matrix. The superiority of using a GBLUP with weighted G-matrix over GBLUP with an original unweighted G matrix was the largest when using a weighting factor of posterior variance, resulting in 1.7 percentage points higher reliability. The second best weighting factors were -log10 (P-value) of a t-test corresponding to the square of the posterior SNP effect from the Bayesian model and -log10 (P-value) of a t-test corresponding to the square of the estimated SNP effect from the linear regression model, followed by the square of estimated SNP effect and the square of the posterior SNP effect. In addition, group-marker weighting performed better than single-marker weighting in terms of reducing bias of GEBV, and also slightly increased prediction reliability. The differences between weighting factors and scenarios were larger in prediction bias than in prediction accuracy. Finally, weights derived from a data set having a lag up to 3 yr did not reduce reliability of GEBV. The results indicate that posterior SNP variance estimated from a Bayesian mixture model is a good alternative weighting factor, and common weights on group markers with a size of 30 markers is a good strategy when using markers of the 50,000-marker (50K) chip. In a population with gradually increasing reference data, the weights can be updated once every 3 yr. PMID- 25129497 TI - In vitro susceptibility of bovine mastitis pathogens to a combination of penicillin and framycetin: development of interpretive criteria for testing by broth microdilution and disk diffusion. AB - Dry cow therapy is an important part of mastitis control. This therapy typically consists of an antibiotic or antibiotics administered at a single dose by intramammary infusion at dry off to treat or prevent infection by prevalent mastitis pathogens. A combination dry cow therapy consisting of the active components penicillin and framycetin is currently used in several countries. Despite its use, standardized methods for the susceptibility testing of this combination against mastitis pathogens have not been established. In this study, which used Clinical and Laboratory Standards Institute methodology, preliminary interpretive criteria for the broth microdilution minimum inhibitory concentration (MIC) testing of mastitis pathogens to penicillin combined with framycetin (2:1 wt/wt) were established based on the amount of drug achieved and maintained postadministration in the udder. Based on resulting MIC distributions of recent veterinary field isolates and a subset of isolates preselected for resistance to beta-lactams or aminoglycosides and concentrations achieved postadministration, criteria for broth microdilution testing of the combination (susceptible, intermediate, resistant in micrograms per milliliter) were set as follows: Escherichia coli <=8/4, 16/8, >=32/16; Staphylococcus spp. <=2/1, 4/2 8/4, >16/8; Streptococcus uberis and Streptococcus dysgalactiae <0.25/0.12, 0.5/0.25-2/1, >4/2. A disk diffusion test using disks containing 100 MUg of framycetin and 10 IU of penicillin was also developed, and preliminary interpretive criteria (susceptible, intermediate, resistant in millimeters) were set based on correlation to broth MIC values and the minimization of interpretive errors between isolates tested concurrently by broth microdilution and disk diffusion as follows: E. coli >=18, 16-17, <=15; Staphylococcus spp. >=21, 18-20, <=17; Strep. uberis and Strep. dysgalactiae >=21, 19-20, <=18. In addition, ranges for the quality control of the testing of this combination by both broth microdilution and disk diffusion are provided. Based on these criteria and recent veterinary mastitis isolates, 96.0/96.8% of E. coli, 93.7/89.1% of Staph. aureus, 94.6/96.4% coagulase-negative staphylococci, 94.5/97.0% of Strep. uberis, and 96.7/100.0% Strep. dysgalactiae were susceptible to the combination by broth microdilution or disk diffusion, respectively. The availability of these methods will allow for the susceptibility testing of clinical isolates in the field and will also provide a way to monitor for resistance development as this combination is used going forward. PMID- 25129496 TI - Enumeration of clostridia in goat milk using an optimized membrane filtration technique. AB - A membrane filtration technique developed for counting butyric acid bacteria in cow milk was further developed for analysis of goat milk. Reduction of the sample volume, prolongation of incubation time after addition of proteolytic enzyme and detergent, and a novel step of ultrasonic treatment during incubation allowed filtration of goat milk even in the case of somatic cell counts (SCC) exceeding 10(6)/mL. However, filterability was impaired in milk from goats in late lactation. In total, spore counts were assessed in 329 farm bulk goat milk samples. Membrane filtration technique counts were lower than numbers revealed by the classic most probable number technique. Thus, method-specific thresholds for milk to evaluate the risk of late blowing have to be set. As expected, the spore counts of milk samples from suppliers not feeding silage were significantly lower than the spore counts of milk samples from suppliers using silage feeds. Not only were counts different, the clostridial spore population also varied significantly. By using 16S rRNA gene PCR and gene sequencing, 342 strains from 15 clostridial species were identified. The most common Clostridium species were Clostridium tyrobutyricum (40.4%), Clostridium sporogenes (38.3%), Clostridium bifermentans (7.6%), and Clostridium perfringens (5.3%). The 2 most frequently occurring species C. tyrobutyricum and C. sporogenes accounted for 84.7% of the isolates derived from samples of suppliers feeding silage (n=288). In contrast, in samples from suppliers without silage feeding (n=55), these species were detected in only 45.5% of the isolates. PMID- 25129498 TI - Methane emissions among individual dairy cows during milking quantified by eructation peaks or ratio with carbon dioxide. AB - The aims of this study were to compare methods for examining measurements of CH4 and CO2 emissions of dairy cows during milking and to assess repeatability and variation of CH4 emissions among individual dairy cows. Measurements of CH4 and CO2 emissions from 36 cows were collected in 3 consecutive feeding periods. In the first period, cows were fed a commercial partial mixed ration (PMR) containing 69% forage. In the second and third periods, the same 36 cows were fed a high-forage PMR ration containing 75% forage, with either a high grass silage or high maize silage content. Emissions of CH4 during each milking were examined using 2 methods. First, peaks in CH4 concentration due to eructations during milking were quantified. Second, ratios of CH4 and CO2 average concentrations during milking were calculated. A linear mixed model was used to assess differences between PMR. Variation in CH4 emissions was observed among cows after adjusting for effects of lactation number, week of lactation, diet, individual cow, and feeding period, with coefficients of variation estimated from variance components ranging from 11 to 14% across diets and methods of quantifying emissions. No significant difference was detected between the 3 PMR in CH4 emissions estimated by either method. Emissions of CH4 calculated from eructation peaks or as CH4 to CO2 ratio were positively associated with forage dry matter intake. Ranking of cows according to CH4 emissions on different diets was correlated for both methods, although rank correlations and repeatability were greater for CH4 concentration from eructation peaks than for CH4-to-CO2 ratio. We conclude that quantifying enteric CH4 emissions either using eructation peaks in concentration or as CH4-to-CO2 ratio can provide highly repeatable phenotypes for ranking cows on CH4 output. PMID- 25129499 TI - A pregnancy detection assay using milk samples: evaluation and considerations. AB - Two experiments were conducted to evaluate a pregnancy-detection assay based on the measurement of pregnancy-associated glycoproteins (PAG) in milk samples. In experiment 1, milk samples were collected on the day of first pregnancy check (33 52 d postinsemination; n=119) or second check (60-74 d postinsemination; n=60). The accuracy in identification of pregnant and nonpregnant cows was 99% at first check. Only 6% of samples were found to be within an intermediate range of PAG concentrations and classified as requiring recheck by the assay. At second check, the accuracy of the assay was 98%. Fifteen percent of these samples were classified as requiring recheck. In experiments 2a (n=17 cows) and 2b (n=16 cows), milk and plasma samples were collected from cows at weekly intervals beginning 2 (experiment 2a) or 4 d (experiment 2b) after insemination. The earliest time point at which pregnant cows were accurately classified as pregnant by the assay was on d 30 postinsemination. A transient decline in PAG levels into the intermediate range was observed on d 46 to 72 postinsemination. This coincides with the time of recheck in experiment 1. Results obtained with the plasma samples were essentially the same. The accuracy of pregnancy identification based on milk samples from nonpregnant and pregnant cows was 99%. Levels of PAG in milk were useful in identifying 6 incidences of embryonic mortality. No consistent relationship was noted between the timing of the decline in PAG levels and the timing of luteal regression in this small number of cows. PMID- 25129500 TI - Interaction between milk allowance and fat content of the starter feed on performance of Holstein calves. AB - Sixty-six Holstein male calves [42 +/- 6.0 kg of body weight (BW) and 12 +/- 3.1 d of age] were housed individually and allocated to 1 of 4 treatments following a 2 * 2 factorial complete randomized design to assess the potential interaction between milk replacer (MR) allowance and fat content in the starter feed. Thus, 4 treatments were evaluated: a low-fat (4.1% fat; LF) starter feed offered along with 4 L/d of MR (4 LF), a high-fat (11.2% fat; HF) starter feed plus 4 L/d of MR (4 HF), a LF starter feed offered with 6 L/d of MR (6LF), and an HF starter feed offered with 6 L/d of MR (6 HF). Calves were fed either 4 or 6 L/d of MR (25% crude protein and 19.2% fat) in 2 offers (0800 and 1630 h) and had ad libitum access to either an LF or an HF starter feed (21.4 and 22.3% crude protein). Calves were weaned at wk 6 of study by halving the daily MR allowance for 1 wk. Individual MR and starter feed intakes were recorded daily and BW was determined weekly. A glucose tolerance test was performed on d 30 of study to evaluate the effects of increased energy provision on glucose metabolism. Apparent feed digestibility was measured for the last 5 d of study. Overall, fat content of starter feed had no effect on solid feed intake. However, during wk 8 of study (after weaning), calves in the LF treatment had greater starter feed intake than HF calves. Calves on 6 L/d of MR had greater BW than calves fed 4 L/d from the second week of study until weaning. After weaning, 6 LF calves had lesser BW than 6 HF calves. Calves on 6 L/d of MR had greater average daily gain than calves fed 4 L/d, and 6 HF calves tended to have the greatest average daily gain. Glucose clearance rate tended to be lesser for HF than for LF calves. In conclusion, offering 6 L/d of MR increased growth performance before weaning and, when offering 6 L/d of MR, feeding a high-fat starter feed resulted in the greatest BW after weaning. PMID- 25129501 TI - Effect of curd washing on the properties of reduced-calcium and standard-calcium Cheddar cheese. AB - Washed (W) and nonwashed (NW) variants of standard (SCa) and reduced-calcium (RCa) Cheddar cheeses were made in triplicate, ripened for a 270-d period, and analyzed for composition and changes during maturation. Curd washing was applied to cheeses to give a target level of lactose plus lactic acid in cheese moisture of 3.9 g/100 g in the W cheese, compared with a value of 5.3 g/100 g of lactose plus lactic acid in cheese moisture in the control NW cheeses. The 4 cheese types were denoted standard calcium nonwashed (SCaNW), standard calcium washed (SCaW), reduced-calcium nonwashed (RCaNW), and reduced-calcium washed (RCaW). The mean calcium level was 760 mg/100 g in the SCaNW and SCaW and 660 mg/100 g in the RCaNW and RCaW cheeses. Otherwise the gross composition of all cheeses was similar, each with protein, fat, and moisture levels of ~26, 32, and 36 g/100 g, respectively. Curd washing significantly reduced the mean level of lactic acid in the SCaW cheese and residual lactose in both SCaW and RCaW cheeses. The mean pH of the standard-calcium cheese over the 270-d ripening period increased significantly with curd washing and ripening time, in contrast to the reduced calcium cheese, which was not affected by the latter parameters. Otherwise curd washing had little effect on changes in populations of starter bacteria or nonstarter lactic acid bacteria, proteolysis, rheology, or color of the cheese during ripening. Descriptive sensory analysis at 270 d indicated that the SCaW cheese had a nuttier, sweeter, less fruity, and less rancid taste than the corresponding SCaNW cheese. In contrast, curd washing was not as effective in discriminating between the RCaW and RCaNW cheeses. The RCaW cheese had a more buttery, caramel odor and flavor, and a more bitter, less sweet, and nutty taste than the SCaW cheese, whereas the RCaNW had a more pungent and less fruity flavor, a less fruity odor, a saltier, more-bitter, and less acidic taste, and a more astringent mouthfeel than SCaNW. Washing of curd during manufacture provides a means of reducing the contents of lactic acid and residual lactose, increasing pH, and altering the sensory properties of Cheddar cheese, with the level of these effects being significantly less pronounced as the calcium content was reduced. PMID- 25129502 TI - Investigation of bacterial and fungal diversity in tarag using high-throughput sequencing. AB - This is the first study on the bacterial and fungal community diversity in 17 tarag samples (naturally fermented dairy products) through a metagenomic approach involving high-throughput pyrosequencing. Our results revealed the presence of a total of 47 bacterial and 43 fungal genera in all tarag samples, in which Lactobacillus and Galactomyces were the predominant genera of bacteria and fungi, respectively. The number of some microbial genera, such as Lactococcus, Acetobacter, Saccharomyces, Trichosporon, and Kluyveromyces, among others, was found to vary between different samples. Altogether, our results showed that the microbial flora in different samples may be stratified by geographic region. PMID- 25129503 TI - NMO spectrum of disorders: a paradigm for astrocyte-targeting autoimmunity and its implications for MS and other CNS inflammatory diseases. AB - When studying a rare or orphan disease, we hope to shed light on more prevalent syndromes. Neuromyelitis optica (NMO), also known as Devic's disease, is a rare disease with a prevalence of about 4 in 100,000. Since 2005 when the anti Aquaporin 4 (AQP4) NMO autoantibody was discovered by Lennon's group at the Mayo clinic, an enormous amount of data have been acquired on the pathogenesis of the disease. A review of the literature showed 47 relevant publications in 2004, compared with 353 in 2013. The auto-antigen AQP4 is expressed on the astrocytic foot processes suggesting a role for astrocytes in the pathogenesis of the disease. However, the astrocytes might play a more active role than has previously been suggested in the immune cascade of NMO pathology. Here we will review epidemiological, clinical diagnostic and therapeutic aspects of NMO and highlight the possible role of astrocytes as major direct and indirect players in the pathogenesis of NMO and related CNS inflammatory diseases. PMID- 25129504 TI - Thymic CCL2 influences induction of T-cell tolerance. AB - Thymic epithelial cells (TEC) and dendritic cells (DC) play a role in T cell development by controlling the selection of the T cell receptor repertoire. DC have been described to take up antigens in the periphery and migrate into the thymus where they mediate tolerance via deletion of autoreactive T cells, or by induction of natural regulatory T cells. Migration of DC to thymus is driven by chemokine receptors. CCL2, a major ligand for the chemokine receptor CCR2, is an inflammation-associated chemokine that induces the recruitment of immune cells in tissues. CCL2 and CCR2 are implicated in promoting experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. We here show that CCL2 is constitutively expressed by endothelial cells and TEC in the thymus. Transgenic mice overexpressing CCL2 in the thymus showed an increased number of thymic plasmacytoid DC and pronounced impairment of T cell development. Consequently, CCL2 transgenic mice were resistant to EAE. These findings demonstrate that expression of CCL2 in thymus regulates DC homeostasis and controls development of autoreactive T cells, thus preventing development of autoimmune diseases. PMID- 25129506 TI - Invasive lobular breast cancer and its variants: how special are they for systemic therapy decisions? AB - The WHO classification of breast tumors distinguishes, besides invasive breast cancer 'of no special type' (former invasive ductal carcinoma, representing 60 70% of all breast cancers), 30 special types, of which invasive lobular carcinoma (ILC) is the most common (5-15%). We review the literature on (i) the specificity and heterogeneity of ILC biology as documented by various analytical techniques, including the results of molecular testing for risk of recurrence; (ii) the impact of lobular histology on prediction of prognosis and effect of systemic therapies in patients. Though it is generally admitted that ILC has a better prognosis than IDC, is endocrine responsive, and responds poorly to chemotherapy, currently available data do not unanimously support these assumptions. This review demonstrates some lack of specific data and a need for improving clinical research design to allow oncologists to make informed systemic therapy decisions in patients with ILC. Importantly, future studies should compare various endpoints in ILC breast cancer patients among the group of hormonosensitive breast cancer. PMID- 25129505 TI - Evaluation of textile substrates for dispensing synthetic attractants for malaria mosquitoes. AB - BACKGROUND: The full-scale impact of odour-baited technology on the surveillance, sampling and control of vectors of infectious diseases is partly limited by the lack of methods for the efficient and sustainable dispensing of attractants. In this study we investigated whether locally-available and commonly used textiles are efficient substrates for the release of synthetic odorant blends attracting malaria mosquitoes. METHODS: The relative efficacy of (a) polyester, (b) cotton, (c) cellulose + polyacrylate, and (d) nylon textiles as substrates for dispensing a synthetic odour blend (Ifakara blend 1(IB1)) that attracts malaria mosquitoes was evaluated in western Kenya. The study was conducted through completely randomized Latin square experimental designs under semi-field and field conditions. RESULTS: Traps charged with IB1-impregnated polyester, cotton and cellulose + polyacrylate materials caught significantly more female Anopheles gambiae sensu stricto (semi-field conditions) and An. gambiae sensu lato (field conditions) mosquitoes than IB1-treated nylon (P = 0.001). The IB1-impregnated cellulose + polyacrylate material was the most attractive to female An. funestus mosquitoes compared to all other dispensing textile substrates (P < 0.001). The responses of female An. funestus mosquitoes to IB1-treated cotton and polyester were equal (P = 0.45). Significantly more female Culex mosquitoes were attracted to IB1-treated cotton than to the other treatments (P < 0.001). Whereas IB1 impregnated cotton and cellulose + polyacrylate material attracted equal numbers of female Mansonia mosquitoes (P = 0.44), the catches due to these two substrates were significantly higher than those associated with the other substrates (P < 0.001). CONCLUSION: The number and species of mosquitoes attracted to a synthetic odour blend is influenced by the type of odour-dispensing material used. Thus, surveillance and intervention programmes for malaria and other mosquito vectors using attractive odour baits should select an odour-release material that optimizes the odour blend. PMID- 25129507 TI - One-pot synthesis of GO/AgNPs/luminol composites with electrochemiluminescence activity for sensitive detection of DNA methyltransferase activity. AB - DNA methyltransferases catalyze the transfer of a methyl group from S adenosylmethionine to the target adenine or cytosine, eventually inducing the DNA methylation in both prokaryotes and eukaryotes. Herein, we developed a novel electrochemiluminescence biosensor to quantify DNA adenine methylation (Dam) methyltransferase (MTase) employing signal amplification of GO/AgNPs/luminol composites to enhance the assay sensitivity. The method was developed by designing a capture probe DNA, which was immobilized on gold electrode surface, to hybridize with azide complementary DNA to form the azide-terminated dsDNA. Then, alkynyl functionalized GO/AgNPs/luminol composites as the signal probe were immobilized to azide-terminated dsDNA modified electrode via click chemistry, resulting in a high electrochemiluminescence (ECL) signal. Once the DNA hybrid was methylated (under catalysis of Dam MTase) and further cleaved by Dpn I endonuclease (a site-specific endonuclease recognizing the duplex symmetrical sequence of 5'-G-Am-T-C-3'), GO/AgNPs/luminol composites release from the electrode surface to the solution, leading to significant reduction of the ECL signal. The change of the ECL intensity is related to the methylation status and MTase activity, which forms the basis of MTase activity assay and site-specific methylation determination. This novel strategy can be further used as a universal method for other transferase determination by designing various transferase specific DNA sequences. In addition, this method can be used for the screening of antimicrobial drugs and has a great potential to be further applied in early clinical diagnosis. PMID- 25129508 TI - Ultrasensitive electrochemical immunoassay for CEA through host-guest interaction of beta-cyclodextrin functionalized graphene and Cu@Ag core-shell nanoparticles with adamantine-modified antibody. AB - A novel non-enzymatic immunoassay was designed for ultrasensitive electrochemical detection of carcino-embryonic antigen (CEA) using beta-cyclodextrin functionalized Cu@Ag (Cu@Ag-CD) core-shell nanoparticles as labels and beta cyclodextrin functionalized graphene nanosheet (CD-GN) as sensor platform. CD-GN has excellent conductivity which promoted the electric transmission between base solution and electrode surface and enhanced sensitivity of immunosensor. In addition, owing to supramolecular recognition of CD-GN for the guest molecule, quite a few synthesized adamantine-modified primary antibodies (ADA-Ab1) were immobilized on the CD-GN by supramolecular host-guest interaction between CD and ADA. Cu@Ag-CD as a signal tag could be captured by ADA-modified secondary antibody (ADA-Ab2) through a host-guest interaction, leading to a large loading of Cu@Ag nanoparticles with high electrical conductivity and catalytic activity. The fabricated immunosensor exhibits excellent analytical performance for the measurement of CEA with wide range linear (0.0001-20 ng/mL), low detection limit (20 fg/mL), good sensitivity, reproducibility and stability, which provide an enormous application prospect in clinical diagnostics. PMID- 25129510 TI - Electrogenerated chemiluminescence behavior of peptide nanovesicle and its application in sensing dopamine. AB - The electrogenerated chemiluminescence (ECL) behavior of the bioinspired peptide nanovesicles (PNVs) was reported for the first time. The PNVs modified glassy carbon electrodes have shown a stable and efficient cathodic ECL signal with K2S2O8 as coreactant in aqueous solution. The possible ECL reaction mechanism was proposed. Dopamine (DA) was chosen as a model analyte to study the potential of the PNVs in the ECL analytical application. It was found that the ECL intensity of the PNVs was effectively increased by trace amounts of DA. The limit of detection was estimated to be 3.15 pM (S/N=3). These results suggest that the PNVs could be a new class of promising materials for the ECL design and bioassays in the future due to their fascinating features, such as excellent biocompatibility, tunable composition as well as capability of molecular recognition. PMID- 25129509 TI - Engineering plasmonic nanorod arrays for colon cancer marker detection. AB - Engineering plasmonic nanomaterials or nanostructures towards ultrasensitive biosensing for disease markers or pathogens is of high importance. Here we demonstrate a systematic approach to tailor effective plasmonic nanorod arrays by combining both comprehensive numerical discrete dipole approximations (DDA) simulation and transmission spectroscopy experiments. The results indicate that 200*50 nm nanorod arrays with 300*500 nm period provide the highest figure of merit (FOM) of 2.4 and a sensitivity of 310 nm/RIU. Furthermore, we demonstrate the use of nanorod arrays for the detection of single nucleotide polymorphism in codon 12 of the K-ras gene that are frequently occurring in early stages of colon cancer, with a sensitivity down to 10 nM in the presence of 100-fold higher concentration of the homozygous genotypes. Our work shows significant potential of nanorod arrays towards point-of-care applications in diagnosis and clinical studies. PMID- 25129511 TI - One-pot synthesis of 3-dimensional reduced graphene oxide-based hydrogel as support for microbe immobilization and BOD biosensor preparation. AB - We report a hydrothermal method to prepare reduced graphene oxide (rGO)-based hydrogel (Gel(rGONR)), using neutral red (NR) to mediate the assembly of rGO sheets and tune the pore size of Gel(rGONR). A series of techniques including scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Raman spectroscopy and BET were employed to characterize the physico-chemical properties of Gel(rGONR). A large pore size of up to 20 um and interconnected porous structure of Gel(rGONR) were obtained. Gel(rGONR) was used as a support for immobilizing microbe (denoted as Gel(rGONR-M)), which showed ~3.3 times more load mass of microbe than commonly used supports (i.e., activated carbon and carbon fiber felt) and 2.5 times higher biodegradation efficiency (BE) than carbon fiber felt. Further use of Gel(rGONR-M) as a biocatalyst for establishing a BOD biosensor exhibits a linear range of 2-64 mg O L(-1) and a detection limit 0.4 mg O L(-1) for glucose-glutamic acid (GGA). Moreover, our proposed BOD detection strategy shows a long-term viability over one year and stability up to 2 months with a relative standard deviation of 2.1%. Our results demonstrated the great potential of employing Gel(rGONR) as a microbe immobilization support for biosensor development. PMID- 25129512 TI - A novel modified electrode as GC/PPy-AuNPs-rGO/L-Cys/Ag@MUA nanostructure configuration for determination of CCP and CRP antibodies in human blood serum samples. AB - In this work, silver nanoparticles were synthesized and stabilized with 11 mercaptoundecanoateanions to produce a new Ag@MUA core shell structure, and its utilizing for fabrication of a new sensing film. Gold nanoparticles (AuNPs) were electrochemically produced and simultaneously immobilized into the electropolymerized polypyrrole (PPy) film with the reduced graphene oxide (rGO). The Ag@MUA was then grafted to the surface of GC/PPy-AuNPs-rGO film using L cysteine (L-Cys) linker agent and trifluoromethanesulfonic anhydride (TF2O), at ambient temperature and under the electrode stirring. The characterization of the sensor was studied by scanning electron microscopy, electrochemical impedance spectroscopy, cyclic and square wave voltammetry techniques. The utility of the modified electrode for clinical diagnosis has been successfully demonstrated by the analysis of human blood serums with a certified CRP and CCP content. Thus, the proposed sensor shows simple preparation, accuracy and precision in the analysis of cytochrome c protein (CCP) and C-reactive protein (CRP (with less side interferences. PMID- 25129513 TI - Green synthesis and molecular recognition ability of patuletin coated gold nanoparticles. AB - Patuletin isolated from Tagetespatula was used as a capping and reducing agent to synthesize in one pot gold nanoparticles capped with patuletin. Conjugation of gold with patuletin was confirmed by FT-IR and UV-visible spectroscopy and amount of patuletin conjugated to gold nanoparticles was found to be 63.2% by weight. Particle sizes were measured by atomic force microscopy (AFM) and were found to have a mean diameter of about 45 nm. Patuletin-coated gold nanoparticles were found to be highly fluorescent. To examine their potential as chemical sensors, they were contacted with fourteen different drugs. Of these drugs, only one, piroxicam, was found to quench luminescence. Quenching obeyed Beer's law in a concentration range of 20-260 uM. Important for molecular recognition applications, fluorescence quenching by piroxicam was not affected by pH variation, elevated temperatures, addition of other drugs and addition of blood plasma to the colloidal suspensions. PMID- 25129514 TI - Epithelial-derived nuclear IL-33 aggravates inflammation in the pathogenesis of reflux esophagitis. AB - BACKGROUND: IL-33 is a new tissue-derived cytokine constitutively expressed in epithelial cells and plays a role in sensing damage caused by inflammatory diseases. The function of IL-33 in the esophageal mucosa has not been previously described. Accordingly, we examined the expression of IL-33 and its role in the pathogenesis of reflux esophagitis (RE). METHODS: IL-33 in the esophageal mucosa of RE patients and in an in vitro stratified normal esophageal squamous epithelial model was examined at the messenger RNA and protein levels. The correlation of the level of IL-33 and IL-8 or IL-6 was examined. Cell layers were stimulated with bile acids and cytokines. IL-33 was knocked down by small interfering RNA (siRNA). Pharmacological inhibitors and signal transducer and activator of transcription 1 (STAT1) siRNA were used. RESULTS: IL-33 was significantly upregulated in RE patients, and was located in the nuclei of basal and suprabasal layers. Upregulated IL-33 messenger RNA expression was correlated with IL-8 and IL-6 expression. In vitro, IL-33 was upregulated in the nuclei of basal and suprabasal layers by interferon-gamma (IFNgamma), and the upregulation was aggravated by the combination of deoxycholic acid (DCA) and IFNgamma. IL-33 knockdown dampened IFNgamma- and DCA-induced IL-8 and IL-6 production. IFNgamma induced IL-33 was inhibited by a Janus kinase inhibitor, a p38 mitogen-activated protein kinase inhibitor, and STAT1 siRNA. CONCLUSIONS: Nuclear IL-33 is upregulated in erosive mucosa of RE patients and is correlated with IL-8 and IL-6 levels. The normal esophageal epithelial model enables us to show for the first time that epithelial-cell-derived nuclear but not exogenous IL-33 is located upstream of the production of inflammatory cytokines and can aggravate the inflammation. PMID- 25129515 TI - A cluster-randomized controlled trial to assess the effectiveness of using 15% DEET topical repellent with long-lasting insecticidal nets (LLINs) compared to a placebo lotion on malaria transmission. AB - BACKGROUND: Long-lasting insecticidal nets (LLINs) have limited effect on malaria transmitted outside of sleeping hours. Topical repellents have demonstrated reduction in the incidence of malaria transmitted in the early evening. This study assessed whether 15% DEET topical repellent used in combination with LLINs can prevent greater malaria transmission than placebo and LLINs, in rural Tanzania. METHODS: A cluster-randomized, placebo-controlled trial was conducted between July 2009 and August 2010 in a rural Tanzanian village. Sample size calculation determined that 10 clusters of 47 households with five people/household were needed to observe a 24% treatment effect at the two-tailed 5% significance level, with 90% power, assuming a baseline malaria incidence of one case/person/year. Ten clusters each were randomly assigned to repellent and control groups by lottery. A total of 4,426 individuals older than six months were enrolled. All households in the village were provided with an LLIN per sleeping space. Repellent and placebo lotion was replaced monthly. The main outcome was rapid diagnostic test (RDT)-confirmed malaria measured by passive case detection (PCD). Incidence rate ratios were estimated from a Poisson model, with adjustment for potential confounders, determined a priori. According-to protocol approach was used for all primary analyses. RESULTS: The placebo group comprised 1972.3 person-years with 68.29 (95% C.I 37.05-99.53) malaria cases/1,000 person-years. The repellent group comprised 1,952.8 person-years with 60.45 (95% C.I 48.30-72.60) cases/1,000 person-years, demonstrating a non significant 11.44% reduction in malaria incidence rate in this group, (Wilcoxon rank sum z=0.529, p=0.596). Principal components analysis (PCA) of the socio economic status (SES) of the two groups demonstrated that the control group had a higher SES (Pearson's chi square=13.38, p=0.004). CONCLUSIONS: Lack of an intervention effect was likely a result of lack of statistical power, poor capture of malaria events or bias caused by imbalance in the SES of the two groups. Low malaria transmission during the study period could have masked the intervention effect and a larger study size was needed to increase discriminatory power. Alternatively, topical repellents may have no impact on malaria transmission in this scenario. Design and implementation of repellent intervention studies is discussed. TRIAL REGISTRATION: The trial was registered ISRCTN92202008--http://www.controlled-trials.com/ISRCTN92202008. PMID- 25129516 TI - Value of CMR for the differential diagnosis of cardiac masses. AB - OBJECTIVES: The goal of this study was to evaluate the diagnostic value of CMR features for the differential diagnosis of cardiac masses. BACKGROUND: Differentiation of cardiac tumors and thrombi and differentiation of benign from malignant cardiac neoplasms is often challenging but important in clinical practice. Studies assessing the value of cardiac magnetic resonance (CMR) in this regard are scarce. METHODS: We reviewed the CMR scans of patients with a definite cardiac thrombus or tumor. Mass characteristics on cine, T1-weighted turbo spin echo (T1w-TSE) and T2-weighted turbo spin echo (T2w-TSE), contrast first-pass perfusion (FPP), post-contrast inversion time (TI) scout, and late gadolinium enhancement (LGE) sequences were analyzed. RESULTS: There were 84 thrombi, 17 benign tumors, and 25 malignant tumors in 116 patients. Morphologically, thrombi were smaller (median area 1.6 vs. 8.5 cm(2); p < 0.0001), more homogeneous (99% vs. 46%; p < 0.0001), and less mobile (13% vs. 33%; p = 0.007) than tumors. Hyperintensity compared with normal myocardium on T2w-TSE, FPP, and LGE were more common in tumors than in thrombi (85% vs. 42%, 70% vs. 4%, and 71% vs. 5%, respectively; all p < 0.0001). A pattern of hyperintensity/isointensity (compared with normal myocardium) with short TI and hypointensity with long TI was very frequent in thrombi (94%), rare in tumors (2%), and had the highest accuracy (95%) for the differentiation of both entities. Regarding the characterization of neoplastic masses, malignant tumors were larger (median area 11.9 vs. 6.3 cm(2); p = 0.006) and more frequently exhibited FPP (84% vs. 47%; p = 0.03) and LGE (92% vs. 41%; p = 0.001). The ability of CMR features to distinguish benign from malignant neoplasms was moderate, with LGE showing the highest accuracy (79%). CONCLUSIONS: CMR features demonstrated excellent accuracy for the differentiation of cardiac thrombi from tumors and can be helpful for the distinction of benign versus malignant neoplasms. PMID- 25129517 TI - Compressed sensing single-breath-hold CMR for fast quantification of LV function, volumes, and mass. AB - OBJECTIVES: The purpose of this study was to compare a novel compressed sensing (CS)-based single-breath-hold multislice magnetic resonance cine technique with the standard multi-breath-hold technique for the assessment of left ventricular (LV) volumes and function. BACKGROUND: Cardiac magnetic resonance is generally accepted as the gold standard for LV volume and function assessment. LV function is 1 of the most important cardiac parameters for diagnosis and the monitoring of treatment effects. Recently, CS techniques have emerged as a means to accelerate data acquisition. METHODS: The prototype CS cine sequence acquires 3 long-axis and 4 short-axis cine loops in 1 single breath-hold (temporal/spatial resolution: 30 ms/1.5 * 1.5 mm(2); acceleration factor 11.0) to measure left ventricular ejection fraction (LVEF(CS)) as well as LV volumes and LV mass using LV model based 4D software. For comparison, a conventional stack of multi-breath-hold cine images was acquired (temporal/spatial resolution 40 ms/1.2 * 1.6 mm(2)). As a reference for the left ventricular stroke volume (LVSV), aortic flow was measured by phase-contrast acquisition. RESULTS: In 94% of the 33 participants (12 volunteers: mean age 33 +/- 7 years; 21 patients: mean age 63 +/- 13 years with different LV pathologies), the image quality of the CS acquisitions was excellent. LVEF(CS) and LVEF(standard) were similar (48.5 +/- 15.9% vs. 49.8 +/- 15.8%; p = 0.11; r = 0.96; slope 0.97; p < 0.00001). Agreement of LVSV(CS) with aortic flow was superior to that of LVSV(standard) (overestimation vs. aortic flow: 5.6 +/- 6.5 ml vs. 16.2 +/- 11.7 ml, respectively; p = 0.012) with less variability (r = 0.91; p < 0.00001 for the CS technique vs. r = 0.71; p < 0.01 for the standard technique). The intraobserver and interobserver agreement for all CS parameters was good (slopes 0.93 to 1.06; r = 0.90 to 0.99). CONCLUSIONS: The results demonstrated the feasibility of applying the CS strategy to evaluate LV function and volumes with high accuracy in patients. The single-breath-hold CS strategy has the potential to replace the multi-breath-hold standard cardiac magnetic resonance technique. PMID- 25129519 TI - Practical guidance in echocardiographic assessment of global longitudinal strain. PMID- 25129518 TI - The natural history of left ventricular geometry in the community: clinical correlates and prognostic significance of change in LV geometric pattern. AB - OBJECTIVES: This study sought to evaluate pattern and clinical correlates of change in left ventricular (LV) geometry over a 4-year period in the community; it also assessed whether the pattern of change in LV geometry over 4 years predicts incident cardiovascular disease (CVD), including myocardial infarction, heart failure, and cardiovascular death, during an additional subsequent follow up period. BACKGROUND: It is unclear how LV geometric patterns change over time and whether changes in LV geometry have prognostic significance. METHODS: This study evaluated 4,492 observations (2,604 unique Framingham Heart Study participants attending consecutive examinations) to categorize LV geometry at baseline and after 4 years. Four groups were defined on the basis of the sex specific distributions of left ventricular mass (LVM) and relative wall thickness (RWT) (normal: LVM and RWT <80th percentile; concentric remodeling: LVM <80th percentile but RWT >=80th percentile; eccentric hypertrophy: LVM >=80th percentile but RWT <80th percentile; and concentric hypertrophy: LVM and RWT >=80th percentile). RESULTS: At baseline, 2,874 of 4,492 observations (64%) had normal LVM and RWT. Participants with normal geometry or concentric remodeling progressed infrequently (4% to 8%) to eccentric or concentric hypertrophy. Change from eccentric to concentric hypertrophy was uncommon (8%). Among participants with concentric hypertrophy, 19% developed eccentric hypertrophy within the 4 year period. Among participants with abnormal LV geometry at baseline, a significant proportion (29% to 53%) reverted to normal geometry within 4 years. Higher blood pressure, greater body mass index (BMI), advancing age, and male sex were key correlates of developing an abnormal geometry. Development of an abnormal LV geometric pattern over 4 years was associated with increased CVD risk (140 events) during a subsequent median follow-up of 12 years (adjusted-hazards ratio: 1.59; 95% confidence interval: 1.04 to 2.43). CONCLUSIONS: The longitudinal observations in the community suggest that dynamic changes in LV geometric pattern over time are common. Higher blood pressure and greater BMI are modifiable factors associated with the development of abnormal LV geometry, and such progression portends an adverse prognosis. PMID- 25129520 TI - Educational intervention to reduce outpatient inappropriate echocardiograms: a randomized control trial. AB - OBJECTIVES: This study sought to prospectively study the impact of an appropriate use criteria (AUC)-based educational intervention on outpatient transthoracic echocardiography (TTE) ordering by physicians-in-training. BACKGROUND: AUC were developed in response to concerns about inappropriate utilization. It is unknown whether an educational intervention can reduce inappropriate outpatient TTE. METHODS: We conducted a randomized control trial in which physicians-in-training were randomized to an AUC-based educational intervention or a control group at an academic medical center in Boston, Massachusetts. The primary endpoints were the rates of inappropriate and appropriate TTE. RESULTS: For the cardiology physicians-in-training, the proportion of inappropriate TTE was significantly lower in the intervention than in the control group (13% vs. 34%, p < 0.001). As a corollary, the proportion of appropriate TTE ordered by the intervention group was significantly higher than that of the control group (81% vs. 58%, p < 0.001). The odds of ordering an appropriate TTE in the cardiology intervention group was 2.7 (95% confidence interval [CI]: 1.5 to 5.1, p = 0.002) relative to the control group. The internal medicine physicians-in-training ordered a small number of TTE overall, and there was a trend toward significant odds of ordering an appropriate TTE in the intervention group relative to the control group (odds ratio [OR]: 8.1, 95% CI: 0.95 to 69.0, p = 0.055). Six clinical scenarios accounted for 75% of all inappropriate TTE, with the 3 most common inappropriate indications being routine surveillance (<1 year) of known cardiomyopathy without a change in clinical status, routine surveillance of known small pericardial effusion, and routine surveillance of ventricular function with known coronary artery disease and no change in clinical status. CONCLUSIONS: In cardiology fellows with a high rate of ordering inappropriate TTE, an AUC-based educational and feedback intervention reduced the proportion of inappropriate outpatient TTE and increased the proportion of appropriate outpatient TTE. (Educational Intervention to Reduce Outpatient Inappropriate Transthoracic Echocardiograms; NCT01944202). PMID- 25129522 TI - Now you see me, now you don't: iridescence increases the efficacy of lizard chromatic signals. AB - The selective forces imposed by primary receivers and unintended eavesdroppers of animal signals often act in opposite directions, constraining the development of conspicuous coloration. Because iridescent colours change their chromatic properties with viewer angle, iridescence offers a potential mechanism to relax this trade-off when the relevant observers involved in the evolution of signal design adopt different viewer geometries. We used reflectance spectrophotometry and visual modelling to test if the striking blue head coloration of males of the lizard Lacerta schreibeiri (1) is iridescent and (2) is more conspicuous when viewed from the perspective of conspecifics than from that of the main predators of adult L. schreibeiri (raptors). We demonstrate that the blue heads of L. schreiberi show angle-dependent changes in their chromatic properties. This variation allows the blue heads to be relatively conspicuous to conspecific viewers located in the same horizontal plane as the sender, while simultaneously being relatively cryptic to birds that see it from above. This study is the first to suggest the use of angle-dependent chromatic signals in lizards, and provides the first evidence of the adaptive function of iridescent coloration based on its detectability to different observers. PMID- 25129521 TI - Accumulation of fatty acids in Chlorella vulgaris under heterotrophic conditions in relation to activity of acetyl-CoAcarboxylase, temperature, and co immobilization with Azospirillum brasilense [corrected]. AB - The relation between fatty acid accumulation, activity of acetyl-CoA carboxylase (ACC), and consequently lipid accumulation was studied in the microalgae Chlorella vulgaris co-immobilized with the plant growth-promoting bacterium Azospirillum brasilense under dark heterotrophic conditions with Na acetate as a carbon source. In C. vulgaris immobilized alone, cultivation experiments for 6 days showed that ACC activity is directly related to fatty acid accumulation, especially in the last 3 days. In co-immobilization experiments, A. brasilense exerted a significant positive effect over ACC activity, increased the quantity in all nine main fatty acids, increased total lipid accumulation in C. vulgaris, and mitigated negative effects of nonoptimal temperature for growth. No correlation between ACC activity and lipid accumulation in the cells was established for three different temperatures. This study demonstrated that the interaction between A. brasilense and C. vulgaris has a significant effect on fatty acid and lipid accumulation in the microalgae. PMID- 25129523 TI - Staged seton fistulotomy after restorative proctocolectomy with ileal pouch-anal anastomosis accompanied by a decline in anal pressure during manometry. PMID- 25129524 TI - Cecal recurrence after one-stage resection of obstructive rectal cancer with intraoperative colonic lavage through the appendix: a curious coincidence. PMID- 25129525 TI - Massive colonic metastasis from breast cancer 23 years after mastectomy. PMID- 25129526 TI - [Out of hospital emergencies towards a safety culture]. AB - OBJECTIVES: The aim of this study is to measure the degree of safety culture (CS) among healthcare professional workers of an out-of-hospital Emergency Medical Service. Most patient safety studies have been conducted in relation to the hospital rather than pre-hospital Emergency Medical Services. The objective is to analyze the dimensions with lower scores in order to plan futures strategies. MATERIAL AND METHODS: A descriptive study using the AHRQ (Agency for Healthcare Research and Quality) questionnaire. The questionnaire was delivered to all healthcare professionals workers of 061 Advanced Life Support Units of Aragon, during the month of August 2013. RESULTS: The response rate was 55%. Main strengths detected: an adequate number of staff (96%), good working conditions (89%), tasks supported from immediate superior (77%), teamwork climate (74%), and non-punitive environment to report adverse events (68%). Areas for improvement: insufficient training in patient safety (53%) and lack of feedback of incidents reported (50%). CONCLUSIONS: The opportunities for improvement identified focus on the training of professionals in order to ensure safer care, while extending the safety culture. Also, the implementation of a system of notification and registration of adverse events in the service is deemed necessary. PMID- 25129527 TI - [Intervention in elderly patients with multiple morbidities and multiple medications: results of the prescription and the quality of life]. AB - OBJECTIVE: To evaluate the effect of an intervention using STOPP/START criteria and the Garfinkel algorithm on prescription and the health-related quality of life (HRQoL) in elderly patients with multimorbidity and prescribed multiple medications. MATERIAL AND METHOD: A before-after intervention study on 381 patients over 67 years old and prescribed multiple medications by 71 Primary Care doctors. INTERVENTION: The doctors were trained in the STOPP / START criteria and Garfinkel algorithm. Each doctor then reviewed all the drugs of their selected patients and then made appointments with them for an initial medical consultation and clinical assessment. Treatment was modified according to the criteria and the HRQoL measured using the SF-12 questionnaire. Two months later, in a second medical consultation, a new clinical assessment was made and the HRQoL was measured. The dimensions of the HRQoL between the first and the second consultation were compared using the paired Student-t test. RESULTS: The intervention involved the removal of a mean of 1.5 drugs per patient. The dose was modified in 4% of drugs, and 8.9% of patients were prescribed a new drug. Non Steroidal Anti-inflammatory drugs (NSAID), psychoactive drugs and proton pump inhibitors were the most modified. Social Function and Physical Component Summary of the HRQOL improved significantly (P<.05) after intervention. CONCLUSION: The intervention using the Garfinkel algorithm and STOPP -START criteria improved HRQoL and reduced the number of prescribed drugs. PMID- 25129528 TI - Beyond description: comment on "approaching human language with complex networks" by Cong and Liu. PMID- 25129529 TI - Fine structure of the midgut of Sinopanorpa tincta (Navas) (Mecoptera: Panorpidae). AB - Fine structure of the midgut and degeneration of the midgut epithelium of the scorpionfly Sinopanorpa tincta (Navas) adults were investigated using light microscopy and scanning and transmission electron microscopy. The results show that the tubular midgut lacks gastric caeca and is composed of an outer longitudinal and an inner circular muscle layer, a basal lamina, an epithelium and a lumen from the outside to inside. A peritrophic membrane was not found in the lumen. A mass of nodules was observed on the surface of the basal lamina. Three types of cells were recognized in the epithelium: digestive, secretory, and regenerative cells. The digestive cells contain irregular-shaped infoldings in the basal membrane and two types of microvilli in the apical membrane. The secretory cells are characterized by irregular shape and large quantities of secretory granules in the basal cytoplasm. The regenerative cells are triangular in shape and distributed only in the nodules. The epithelial cells are degenerated through programmed cell-death mechanisms (apoptosis and necrosis). The type, function, and degeneration of the epithelial cells of the midgut are briefly discussed. PMID- 25129530 TI - Effect of sporulation medium on wet-heat resistance and structure of Alicyclobacillus acidoterrestris DSM 3922-type strain spores and modeling of the inactivation kinetics in apple juice. AB - Alicyclobacillus acidoterrestris is a spoilage bacterium in fruit juices leading to high economic losses. The present study evaluated the effect of sporulation medium on the thermal inactivation kinetics of A. acidoterrestris DSM 3922 spores in apple juice (pH3.82+/-0.01; 11.3+/-0.1 degrees Brix). Bacillus acidocaldarius agar (BAA), Bacillus acidoterrestris agar (BATA), malt extract agar (MEA), potato dextrose agar (PDA) and B. acidoterrestris broth (BATB) were used for sporulation. Inactivation kinetic parameters at 85, 87.5 and 90 degrees C were obtained using the log-linear model. The decimal reduction times at 85 degrees C (D85 degrees C) were 41.7, 57.6, 76.8, 76.8 and 67.2min; D87.5 degrees C-values were 22.4, 26.7, 32.9, 31.5, and 32.9min; and D90 degrees C-values were 11.6, 9.9, 14.7, 11.9 and 14.1min for spores produced on PDA, MEA, BATA, BAA and BATB, respectively. The estimated z-values were 9.05, 6.60, 6.96, 6.15, and 7.46, respectively. The present study suggests that the sporulation medium affects the wet-heat resistance of A. acidoterrestris DSM 3922 spores. Also, the dipicolinic acid content (DPA) was found highest in heat resistant spores formed on mineral containing media. After wet-heat treatment, loss of internal volume due to the release of DPA from spore core was observed by scanning electron microscopy. Since, there is no standardized media for the sporulation of A. acidoterrestris, the results obtained from this study might be useful to determine and compare the thermal resistance characteristics of A. acidoterrestris spores in fruit juices. PMID- 25129531 TI - A web-based self-management intervention for Bipolar Disorder 'living with bipolar': a feasibility randomised controlled trial. AB - BACKGROUND: Bipolar Disorder (BD) is a severe mental health problem. Psychological interventions are recommended by the National Institute for Health and Care Excellence (NICE) but patients experience severe inequalities in access. This study assessed the feasibility and potential effectiveness of a recovery informed web-based self-management intervention for people with BD. METHODS: An online randomised controlled trial (n=122) compared treatment as usual (TAU) plus the 'Living with Bipolar' (LWB) intervention with a waiting list control (WLC) group. RESULTS: The study recruited to target and the retention rates were high. Participants engaged with the approach. Compared with the WLC, those receiving LWB showed the most robust improvement in psychological and physical domains of quality of life, wellbeing and recovery at the end of the intervention. LIMITATIONS: The trial was not definitive and requires further investigation. CONCLUSIONS: There is preliminary evidence that a web-based treatment approach in BD is feasible and potentially effective. Such interventions could form part of the Improving Access to Psychological Therapy (IAPT) initiative in severe mental health. PMID- 25129532 TI - Dysfunctional traits in obese women and underweight men. AB - BACKGROUND: The prevalence of obesity is rapidly increasing worldwide, together with its comorbidities. Our aim was to assess the emotional traits and affective temperaments, according to various Body Mass Index (BMI) groups, in a large sample. METHODS: Data was collected by a web-survey on psychological and psychiatric measures (BRAINSTEP). The BMI was evaluated by self-reporting and temperament was evaluated by the Affective and Emotional Composite Temperament Scale (AFECTS). The final sample consisted of 10,786 individuals (mean age 27.9 +/- 7.8 years, 70% females). RESULTS: About 40% of the sample had a BMI score higher than normal. The overall BMI score was particularly associated with a higher Desire and a lower Control and Volition (p<0.001 for all), especially in women. Obese females also had significantly lower Coping, Stability, and Caution. In males only, underweight individuals were more fearful and sensitive, and they had a lower Coping and Volition character than normal weight subjects, suggesting a more fragile and immature profile. Linear regression with several adjustments confirmed these associations. Regarding affective temperaments, a Depressive type was more prevalent among underweight subjects, an Obsessive type was associated with a normal BMI, and a Hyperthymic type was apparent in overweight individuals of both genders. Underweight males and females were more prone to having an internalized temperament. LIMITATIONS: Only self-reporting measures were used in a cross-sectional design. CONCLUSIONS: Obese women and underweight men have a more dysfunctional trait profile. Addressing these traits may be important for prevention strategies and, possibly, for weight reduction in women. PMID- 25129534 TI - PTSD prevalence and symptom structure of DSM-5 criteria in adolescents and young adults surviving the 2011 shooting in Norway. AB - BACKGROUND: Diagnostic criteria for Posttraumatic Stress Disorder (PTSD) have been revised for DSM-5. Two key changes include alteration of the clustering of PTSD symptoms and new PTSD symptom criteria related to negative alterations in cognition and mood. In this study, we empirically investigated these changes. METHODS: We interviewed 325 adolescents and young adults who survived the 2011 youth camp shooting at Utoya Island, Norway. The UCLA PTSD Reaction Index for DSM IV was used to assess symptoms of PTSD. In addition, 11 questions were added to assess the four new symptom criteria within the new DSM-5 symptom categories. RESULTS: PTSD prevalence did not differ significantly whether DSM-IV (11.1%) or DSM-5 (11.7%) criteria were used and the Cohen's Kappa for consistency between the diagnoses was 0.061. Confirmatory factor analyses showed that the four-factor structure of the DSM-5 fit the data adequately according to the conceptual model outlined. LIMITATIONS: The homogeneity of this sample of highly exposed subjects may preclude generalization to less severely exposed groups. Also, we did not assess criterion G in regard to symptoms causing clinically significant distress and functional impairment. CONCLUSION: The prevalence of PTSD was quite similar regardless of diagnostic system. The relatively low concordance between the diagnoses has implications for eligibility for a diagnosis of PTSD. PMID- 25129533 TI - Long-term Tai Chi training is related to depressive symptoms among Tai Chi practitioners. AB - BACKGROUND: Due to the close association with physical and psychological health and quality of life, mood disorders, especially depressive symptoms, are an important global public-health issue. It is hypothesized that long-term physical training and mood adjustment may have a beneficial effect on the prevention of the onset of depressive symptoms. The aim of this study was to investigate the relationship between long-term Tai Chi training and depressive symptoms among Tai Chi practitioners. METHODS: This study analyzed a cross-sectional survey including 529 Japanese Tai Chi practitioners. Tai Chi training information, including total training time and a Tai Chi grade, was assessed using a structured questionnaire, and depressive symptoms were evaluated using the 15 item Geriatric Depression Scale (GDS) for subjects aged >=65 and the 20-item Self rating Depressive Scale (SDS) for subjects aged <65 with cut-off points: GDS >=5 and SDS >=11. RESULTS: The prevalence of depressive symptoms was 15.9%. After adjustments for potential confounding factors, the odds ratios of having depressive symptoms by increasing levels of Tai Chi training time were 1.00, 0.64 (0.37-1.11), 0.65 (0.37-1.13), 0.34 (0.18-0.65) (P for trend <0.01). LIMITATIONS: This is a cross-sectional study, and not for making a clinical diagnosis of depressive symptoms. CONCLUSIONS: This study has demonstrated that long-term Tai Chi training is independently related to a lower prevalence of depressive symptoms. These results suggest that long-term Tai Chi training may have a beneficial effect on the prevention of depressive symptoms. Further studies are needed to confirm these findings. PMID- 25129535 TI - Long-term outcomes of intrastromal corneal ring segment implantation for post LASIK ectasia. AB - PURPOSE: To report the long-term results of intrastromal corneal ring segments (ICRS) for postoperative LASIK ectasia. METHOD: In this retrospective interventional cases series, 8 eyes of 6 patients who underwent femtosecond laser assisted ICRS implantation for post-LASIK ectasia were enrolled. Main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), spherical equivalent refraction, and average keratometry (Kavg) values were assessed. RESULTS: Mean+/-SD follow-up was 67+/-21 months (range, 36-96 months). The mean UDVA, CDVA, spherical equivalent refraction, and Kavg values were significantly improved at all postoperative visits when compared to baseline values. No serious complications were observed during follow-up. CONCLUSION: Our long-term findings showed that ICRS yielded improvements in visual acuity, refractive status, and keratometric values without any progression in cases with post-LASIK corneal ectasia. PMID- 25129536 TI - Spectral transmittance of UV-blocking soft contact lenses: a comparative study. AB - BACKGROUND: Three major parts of sunlight consist of visible, ultraviolet and infrared radiation. Exposure to ultraviolet radiation (UVR) can result in a spectrum of skin and ocular diseases. UV-blocking contact lenses help provide protection against harmful UV radiation. We studied the ultraviolet and visible light rays transmission in some soft UV-blocking contact lenses. MATERIAL AND METHODS: Four available tinted soft lenses (Acuvue Moist, Zeiss CONTACT Day 30 Air spheric, Pretty Eyes and Sauflon 56 UV) have been evaluated for UV and visible transmission. One-way ANOVA testing was performed to establish is there a statistically significant difference between the UV regions and visible spectra means for the contact lenses (alpha=0.05). RESULTS: Pretty Eyes, Zeiss CONTACT, Acuvue Moist and Sauflon 56 UV showed UV-B transmittance value of 0.65%, 10.69%, 1.22%, and 5.78%, respectively. Pretty Eyes and Acuvue Moist had UV-A transmittance values of 32% and 34%, Sauflon 56 UV and Zeiss CONTACT had transmittance values of 48% and 43%, respectively. All of the studied lenses transmitted at least 94.6% on the visible spectrum. The results of the one-way ANOVA statistical analysis show that a statistically significant difference exists within the group of contact lenses tested for the visible (p<0.001), UV-B (p<0.001) and UV-A (p<0.001) portions of the spectrum (alpha=0.05). CONCLUSION: Acuvue Moist has the best UV-blocking property and also visible transmission between other tested contact lenses in this study. PMID- 25129537 TI - Revision urethroplasty success is comparable to primary urethroplasty: a comparative analysis. AB - OBJECTIVE: To assess the efficacy and complications of revision urethroplasty compared with urethroplasty-naive controls. MATERIALS AND METHODS: A retrospective analysis was performed of 534 urethroplasties performed by a single surgeon from August 2003 to March 2011. Patient age, stricture length, location, etiology, comorbidities, and type of surgery were recorded. Statistical comparison between the revision cohort and urethroplasty-naive group were made using Fisher, chi(2), and unpaired t tests, with significance at P < .05 (2 tailed). The primary outcome was urethral patency assessed by cystoscopy. Secondary (subjective) outcome measures included erectile dysfunction, pain, urinary tract infection, or chordee at 6 months. RESULTS: A total of 476 patients met inclusion criteria with completed cystoscopic follow-up. Previous urethroplasty had failed in 49 patients (10.3%). Patients undergoing revision urethroplasty were more likely to have stricture in the penile urethra (22.4%; P = .001), to have strictures exceeding 4 cm in length (71.4% vs 54.3%; P = .023), and to require tissue transfer (83.6% vs 65.1%; P = .010). Urethral patency rates did not differ significantly between naive and revision urethroplasty cohorts, with a mean follow-up of 49.9 months (94.6% vs 91.8%; P = .518). The revision group had a higher incidence of chordee (2.7% vs 14.3%; P = .001) and urinary tract infection (3.5% vs 10.2%; P = .04). The rates of erectile dysfunction, scrotal pain, lower urinary tract symptoms, and incontinence did not differ significantly between the 2 groups. CONCLUSION: Revision urethroplasty is an effective treatment option for recurrent stricture after urethroplasty and is comparable to results in urethroplasty-naive patients. Patients undergoing revision urethroplasty are more likely to require tissue transfer and experience higher rates of chordee and urinary tract infection. PMID- 25129538 TI - Reply: To PMID 25129537. PMID- 25129539 TI - Impact of prostatic apical shape and protrusion on early recovery of continence after robot-assisted radical prostatectomy. AB - OBJECTIVE: To investigate the impact of prostatic apical shape from preoperative magnetic resonance imaging on early recovery of urinary continence after robot assisted radical prostatectomy (RARP). MATERIALS AND METHODS: We reviewed the records of 1011 patients who underwent RARP at a tertiary center from October 2007 to March 2013. Patients were stratified into 4 different groups by prostatic apical shapes as shown on preoperative magnetic resonance imaging (groups A-D). The early recovery of urinary continence was defined as 0 or 1 security pad/d within 12 weeks after the surgery. The association between early recovery of continence and various factors was analyzed. RESULTS: Overall, 807 patients (79.8%) showed early recovery of urinary continence. The numbers of patients in groups A, B, C, and D were 88 (8.7%), 478 (47.3%), 167 (16.5%), and 278 (27.5%), respectively. There were no significant differences in the rates of early recovery of urinary continence between different groups (P = .257). On multivariate analysis, the patient's age (odds ratio [OR], 0.960; P = .004), preoperative International Index of Erectile Function-5 score (OR, 1.029; P = .009), neurovascular bundle preservation (OR, 1.586; P = .013), and membranous urethral length (OR, 1.104; P = .001) were revealed as independent prognostic factors in the early recovery of urinary continence. CONCLUSION: The results of our study showed that the prostatic apical shape does not influence the early recovery of urinary continence. We believe this is another strong point of RARP compared with conventional open surgery, particularly for patients with complex type of apical shape. PMID- 25129540 TI - Clinical value of transurethral second resection of bladder tumor: systematic review. AB - OBJECTIVE: To systematically review prospective trials aimed at the role of restaging transurethral resection (reTUR) to define the group of patients with bladder cancer who would benefit. MATERIALS AND METHODS: A systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines was conducted. RESULTS: Of 120 trials, 7 met the inclusion criteria. Most studied populations were high-risk non-muscle invasive bladder cancer patients. Low-risk cancers as well as muscle-invasive disease were analyzed in only 1 trial. Consistently through the publications, reTUR improved staging with the rates of muscle-invasive disease mounting to 17.6% when primary resection was deemed to be complete. Although all trials corroborated staging role of reTUR, only 4 provided recurrence and progression outcomes, the first being significantly lower in the group of second early resection. In 2 studies with the longest follow-up and the greatest number of patients with high-risk non-muscle-invasive bladder cancer, progression rates were found to be improved. In one trial, reTUR was associated with better response to bacille Calmette-Guerin. CONCLUSION: The data convincingly suggest that early second resection improves staging and reduces the recurrence as well as progression rates of high-risk bladder tumors. reTUR brings benefit to those subjected to bacille Calmette-Guerin. However, additional surgery would not modify treatment plan in those with low-risk disease. PMID- 25129541 TI - Editorial comment. PMID- 25129542 TI - The association between testicular microlithiasis and semen parameters in Chinese adult men with fertility intention: experience of 226 cases. AB - OBJECTIVE: To investigate the association between testicular microlithiasis (TM) and semen parameters in Chinese adult men with fertility intention. MATERIALS AND METHODS: We retrospectively reviewed the ultrasonography results of the reproductive system of 16,204 consecutive adult male patients in our hospital with fertility intention from November 2012 to October 2013. TM was diagnosed by scrotal ultrasonography. Patients with TM were divided into classic testicular microlithiasis (CTM) or limited testicular microlithiasis (LTM). The clinical data of CTM, LTM, and non-TM groups, especially of patients in whom sperms were found in semen analysis, were collected and analyzed. RESULTS: There were 226 men (1.39%) diagnosed with TM. The mean age was 28.96 +/- 5.12 years (range, 21-46 years), whereas mean testicular volume was 15.38 +/- 4.90 mL (range, 1.62-31.23 mL). CTM and LTM were detected in 141 (62.39%) and 85 patients (37.61%), respectively. Among 200 patients who underwent semen analysis, sperms were found in 159 men (79.5%; 97 men with CTM and 62 men with LTM). One hundred and twenty cases without TM (ie, non-TM group) were collected in the control group. Sperm concentration, total motility, and percentage of progressively motile of CTM, LTM, and non-TM groups was (38.01 +/- 31.58 million/mL vs 52.31 +/- 33.26 million/mL vs 67.16 +/- 36.94 million/mL; P <.001), (46.03 +/- 23.69% vs 55.37 +/ 24.16% vs 62.08 +/- 20.45%; P <.001), and (35.88 +/- 20.17% vs 43.15 +/- 21.08% vs 47.10 +/- 17.84%; P <.001), respectively. CONCLUSION: TM is associated with worse semen parameters in adult men with fertility intention. The extent of microlithiasis correlates inversely with semen parameters. PMID- 25129544 TI - Gonadoblastoma and selected other aspects of gonadal pathology in young patients with disorders of sex development. AB - Some patients with disorders of sex development (DSDs), previously known as intersex disorders, have abnormal gonadal development and an increased risk of germ cell tumors. Because of their relative rarity, however, many pathologists are unfamiliar with the morphological findings in the gonads of DSD patients and their clinical significance. This review concentrates on some of the most common DSDs where gonadal specimens may come to the attention of pathologists. It highlights the findings in gonadal dysgenesis, a DSD with a spectrum of clinical, pathologic, and molecular features but with the shared attributes of having both Y chromosomal material (even if in very limited amounts) in the gonad and also having mutations or deletions in genes necessary for normal gonadal development, mostly in those upstream of the SOX9 gene. This situation results in testicular tissue lacking normal Sertoli cells, which are now considered an essential element for the normal maturation of the primordial germ cells that migrate to the gonad from the embryonic yolk sac. Germ cells with delayed maturation mimic neoplastic germ cells, but there are both morphological and immunohistochemical differences. If the gonad having germ cells with delayed maturation also harbors the TSPY gene on the GBY locus of the Y chromosome, the cells may undergo neoplastic transformation and result in the distinctive gonadoblastoma, whose pathologic features are explored at length herein, including its potential for variant morphologies, such as a "dissecting" pattern. Another important DSD, the androgen insensitivity syndrome (AIS), is discussed at length, including the varied appearances of the testis and its distinctive lesions-hamartomas and Sertoli cell adenomas. The potential for germ cell neoplasia in the partial AIS is also discussed and contrasted with that of the complete AIS. A third major topic is ovotesticular DSD (true hermaphroditism). The clinical features and morphology of this condition are reviewed, including the arrangements of the tissue components in an ovotestis. Several other DSDs with distinctive gonadal findings are also considered, including Klinefelter syndrome, 5alpha-reductase deficiency, 17beta-hydroxysteroid dehydrogenase deficiency, and female adrenogenital syndrome. PMID- 25129543 TI - Molecular pathways reflecting poor intrauterine growth are found in Wharton's jelly-derived mesenchymal stem cells. AB - STUDY QUESTION: Are molecular pathways reflecting the biology of small for gestational age (SGA) neonates preserved in umbilical cord-derived mesenchymal stem cells (MSCs)? SUMMARY ANSWER: MSCs from SGA newborns were found to express an altered EGR-1-dependent gene network involved in the regulation of cell proliferation and oxidative stress. WHAT IS KNOWN ALREADY: Individuals with suboptimal intrauterine development are at greater risk of metabolic diseases such as type II diabetes, obesity and cardiovascular disease. STUDY DESIGN, SIZE, DURATION: Umbilical cords (n = 283) from the GUSTO (growing up in Singapore towards healthy outcomes) birth cohort study, and primary MSC isolates established from SGA and matched control cases (n = 6 per group), were subjected to gene expression analysis and candidate genes were studied for functional validation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Umbilical cord specimens were derived from babies born at the National University Hospital (NUH) in Singapore. Local ethical approval was obtained. MSC isolates were established in Wharton's jelly and molecular analysis was conducted by gene expression microarrays and RT-PCR. Cells from SGA and control groups were compared in the presence and absence of insulin and candidate gene function was studied via siRNA mediated gene knockdown and over-expression experiments in MSCs. MAIN RESULTS AND THE ROLE OF CHANCE: Using repeated measure ANOVAs, proliferation rates of MSCs isolated from SGA neonates were found to be significantly increased (P < 0.01). In the absence of insulin, EGR-1 levels were found to be significantly reduced in the group of SGA-derived MSCs, whereas EGR-1 expression was found to be up regulated in the same group in the presence of insulin (P < 0.01). EGR-1 was found to induce expression of COX-2 in the SGA group (P < 0.01) and both, EGR-1 and COX-2 stimulated glucose uptake in MSCs (P < 0.01). EGR-1 and COX-2 levels were associated in whole umbilical cords (n = 283, P < 0.01) and EGR-1 positively correlated with abdominal circumference and birthweight (n = 91, P < 0.01 and n = 91, P < 0.01). LIMITATIONS, REASONS FOR CAUTION: Cell models may not entirely reflect the physiology of the host and patient follow-up studies will be necessary for further clinical validation. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that Wharton's jelly-derived MSCs are useful in identifying pathways specific for fetal growth restriction. STUDY FUNDING/COMPETING INTERESTS: This work is supported by the Translational Clinical Research (TCR) Flagship Program on Developmental Pathways to Metabolic Disease funded by the National Research Foundation (NRF) and administered by the National Medical Research Council (NMRC), Singapore- NMRC/TCR/004-NUS/2008'. SICS Investigators are supported through the Agency for Science Technology and Research (A*STAR) funding. No potential conflicts of interest relevant to this article were reported. PMID- 25129545 TI - The Santa Pola saltern as a model for studying the microbiota of hypersaline environments. AB - Multi-pond salterns constitute an excellent model for the study of the microbial diversity and ecology of hypersaline environments, showing a wide range of salt concentrations, from seawater to salt saturation. Accumulated studies on the Santa Pola (Alicante, Spain) multi-pond solar saltern during the last 35 years include culture-dependent and culture-independent molecular methods and metagenomics more recently. These approaches have permitted to determine in depth the microbial diversity of the ponds with intermediate salinities (from 10% salts) up to salt saturation, with haloarchaea and bacteria as the two main dominant groups. In this review, we describe the main results obtained using the different methodologies, the most relevant contributions for understanding the ecology of these extreme environments and the future perspectives for such studies. PMID- 25129546 TI - Gamma knife radiosurgery for the treatment of gynecologic malignancies metastasizing to the brain: clinical article. AB - Gynecologic malignancies represent some of the commonest causes of cancer in the female population. Despite their overall high prevalence, gynecologic malignancies have seldom been reported to metastasize to the brain. The incidence of gynecologic cancers spreading to the brain has been rising, and the optimal management of these patients is not well defined. A retrospective analysis of patients treated over the past ten years with gamma knife radiosurgery (GKRS) for metastatic gynecologic cancer to the brain was performed. Radiographic treatment response, tumor control, metastatic disease progression and survival data were analyzed. Eight patients with ovarian cancer, six patients with endometrial cancer and two separates who carried a diagnosis of cervical cancer or leiomyosarcoma harbored metastatic disease to the brain that was treated with GKRS. The median dose to the tumor margin was 20 Gy (range 10-22 Gy), and the median maximum radiosurgical dose was 31 Gy (range 16-52.9 Gy). Tumor control was achieved in all patients who had follow up imaging studies. Patients with ovarian cancer had prolonged median survival following GKRS compared to patients with endometrial cancer (22.3 vs 8.3 months, p = 0.02). The patient with cervical cancer survived 8 months following her GKRS in the setting of metastatic brain tumor progression, whereas the patient with leiomyosarcoma passed away within several weeks of treatment secondary to disseminated extracranial primary disease. GKRS is a safe and effective means of achieving intracranial tumor control for patients with gynecologic cancer that has spread to the brain. PMID- 25129547 TI - Incidence of medulloblastoma in Canadian children. AB - Medulloblastoma is the most common malignant brain tumor in children. There was a perception of pediatric neuro-oncologists that the incidence had declined in Canada. An epidemiological survey was undertaken to determine the incidence of this tumor in Canada and if a change had indeed occurred. All patients 14 years and under diagnosed with medulloblastoma from 1990 to 2009 inclusive in Canada were included. Data collected included date of diagnosis, age at diagnosis, gender, stage, pathology, treatment, recurrence and current status. Data were analysed for change in incidence over time. Data were obtained on 574 eligible patients. The mean overall incidence per 1,000,000 persons was 4.82 (95 % CI 4.28 5.35) for the study time period. The mean age at diagnosis was 5.8 years, and there was a male predominance. Although there was an increase in incidence over the first three time periods (24 % for 1990-1994, 27.5 % for 1995-1999, 27.7 % for 2000-2004), the most recent time period (2005-2009) showed a decrease (21 %). This was true for male children while the incidence was stable for females. The mean incidence rate was double for children under the age of 5 years (7.92 per million) compared to those over 5 years (3.64 per million).This study showed that from 1990 to 2009 the incidence of medulloblastoma was relatively stable, with a slight decrease in the last five-year time period. PMID- 25129548 TI - Social vulnerability from a social ecology perspective: a cohort study of older adults from the National Population Health Survey of Canada. AB - BACKGROUND: Numerous social factors, generally studied in isolation, have been associated with older adults' health. Even so, older people's social circumstances are complex and an approach which embraces this complexity is desirable. Here we investigate many social factors in relation to one another and to survival among older adults using a social ecology perspective to measure social vulnerability among older adults. METHODS: 2740 adults aged 65 and older were followed for ten years in the Canadian National Population Health Survey (NPHS). Twenty-three individual-level social variables were drawn from the 1994 NPHS and five Enumeration Area (EA)-level variables were abstracted from the 1996 Canadian Census using postal code linkage. Principal Component Analysis (PCA) was used to identify dimensions of social vulnerability. All social variables were summed to create a social vulnerability index which was studied in relation to ten-year mortality. RESULTS: The PCA was limited by low variance (47%) explained by emergent factors. Seven dimensions of social vulnerability emerged in the most robust, yet limited, model: social support, engagement, living situation, self esteem, sense of control, relations with others and contextual socio-economic status. These dimensions showed complex inter-relationships and were situated within a social ecology framework, considering spheres of influence from the individual through to group, neighbourhood and broader societal levels. Adjusting for age, sex, and frailty, increasing social vulnerability measured using the cumulative social vulnerability index was associated with increased risk of mortality over ten years in a Cox regression model (HR 1.04, 95% CI:1.01-1.07, p = 0.01). CONCLUSIONS: Social vulnerability has important independent influence on older adults' health though relationships between contributing variables are complex and do not lend themselves well to fragmentation into a small number of discrete factors. A social ecology perspective provides a candidate framework for further study of social vulnerability among older adults. PMID- 25129550 TI - alpha-linolenic acid concentration and not wounding per se is the key regulator of octadecanoid (oxylipin) pathway activity in rice (Oryza sativa L.) leaves. AB - Using an in vitro system composed of crushed leaf tissues to simulate the wounding response in rice leaves, we established that synthesis of jasmonic acid (JA) and jasmonic acid-isoleucine (JA-Ile) can only occur in unwounded tissue and, in wounded tissue, that only the chloroplast-located section of the octadecanoid pathway is active, resulting in the accumulation of 12-oxo phytodienoic acid (OPDA). We further showed that OPDA accumulation in vitro was inhibited by 90% using the general lipase inhibitor, tetrahydrolipstatin, indicating that production of alpha-linolenic acid was the rate-limiting step in octadecanoid pathway activity in rice following wounding and the enzyme capacity for an active pathway was already present. We confirmed this result by showing that added alpha-linolenic acid stimulated OPDA synthesis in vitro and stimulated OPDA, JA and JA-Ile synthesis in vivo in unwounded tissue. Thus, the response to wounding can be mimicked by the provision of free alpha-linolenic acid. Our results draw attention to the key importance of lipase activity in initiation of JA and JA-Ile biosynthesis and our lack of knowledge of the cognate lipase(s), lipase substrate identity and mechanism(s) of activation in wounded and unwounded tissue. PMID- 25129549 TI - Influence of carotid artery stenting on cognition of elderly patients with severe stenosis of the internal carotid artery. AB - BACKGROUND: The aim of this study was to investigate the influence of carotid artery stenting (CAS) on the cognition and quality of life of elderly patients with severe stenosis of the internal carotid artery. MATERIAL/METHODS: 65 elderly patients with symptomatic severe stenosis of internal carotid artery were recruited into 2 groups: the pharmacotherapy group (n=29) and the CAS group (n=36). Before surgery and 1, 3, 6, and 12 months after surgery, Montreal cognitive assessment (MoCA) was used for the evaluation of cognition and WHOQOL BREF was used for the assessment of quality of life. RESULTS: At 12 months after surgery, total MoCA score and WHOQOL-BREF score in the pharmacotherapy group was significantly reduced when compared with those before surgery (P<0.05). In the CAS group, the total MoCA score, scores of attention and delayed recall, and WHOQOL-BREF score increased significantly at different time points after surgery when compared with those before surgery (P<0.05). Moreover, in CAS group, the MoCA score and WHOQOL-BREF markedly increased gradually over time (P<0.05). Compared with the pharmacotherapy group, cognition and quality of life in the CAS group were improved dramatically during the follow-up period (P<0.05). CONCLUSIONS: Severe stenosis of the internal carotid artery is a cause of cognition impairment, and CAS may improve cognition and quality of life. PMID- 25129551 TI - Prospective, randomized, controlled, and open study in primarily inoperable, stage III non-small cell lung cancer (NSCLC) patients given sequential radiochemotherapy with or without epoetin alfa. AB - BACKGROUND AND PURPOSE: Induction chemotherapy is associated with anemia in non small cell lung cancer (NSCLC) patients undergoing radiotherapy. This randomized, open-label study compared the effect of sequential radiochemotherapy (RCHT) versus RCHT + epoetin alfa (RCHT + EPO), with respect to 2-year overall survival (OS). MATERIAL AND METHODS: Patients ?18 years received sequential RCHT; one arm also received EPO (chemotherapy day 1, when Hb<12 g/dL). Kaplan-Meier analysis with log-rank test, and Cox-regression methods were performed. RESULTS: Of the 385 patients randomized (RCHT + EPO: n = 195; RCHT: n = 190), 78 (RCTH + EPO: 46 [23.6%]; RCHT: 32 [16.8%]) were anemic at baseline. Two-year OS was higher in RCHT + EPO-treated versus RCHT-treated (28.5% [95% CI: 22.2-35.1%] versus 20.6% [95% CI: 15.1-26.8%] [p = 0.2278]), and requirement for RBC transfusion was lower (24/195 [12.3%] versus 61/190 [32.1%]). In anemic (baseline) patients (post hoc analysis), median survival was shorter in RCTH-treated (212 days) versus RCHT + EPO-treated (343 days) (Hazard ratio = 1.62 [95% CI: 0.99-2.63], p = 0.0525). Adverse events were documented in 72.7% (RCHT + EPO: 75.0%; RCHT: 70.5%) patients, and thrombovascular events (TVEs) in 45 patients (RCHT + EPO: 16.7%; RCHT: 7.9%; p = 0.0099). CONCLUSIONS: A statistically non-significant trend for 2 year OS was observed in a sub-group of EPO-treated NSCLC-patients with baseline anemia, although this trend was not maintained in the overall population with inoperable NSCLC. PMID- 25129552 TI - Laparoscopic repair for failed antireflux procedures. AB - BACKGROUND: Minimally invasive procedures have become common, and more reoperations for failed antireflux procedures are performed laparoscopically. We wanted to study the outcomes of laparoscopic reoperations for reflux. METHODS: Medical records of all patients who underwent reoperation without esophageal resection after previous antireflux procedures between January 2000 and October 2012 were reviewed. RESULTS: Seventy-five patients were included in this report: 56 (77%) women and 19 (23%) men. Median age was 58 years. The previous operation was laparoscopic antireflux procedures in 65 (87%) patients. The median interval between the last antireflux procedure and laparoscopic reoperation was 42 months. The median body mass index (BMI) was 28.7. All patients were symptomatic. Intraoperative findings included recurrent hiatal hernia in 47 (63%) patients, incompetent fundoplication in 14 (19%) patients, tight fundoplication in 8 (11%) patients, and tight crura in 2 (3%) patients. Laparoscopic Nissen fundoplication was performed in 57 (76%) patients, partial posterior fundoplication was performed in 12 (16%) patients, partial anterior fundoplication was performed in 3 (4%) patients, removal of crural stitches was performed in 2 patients, and a combination of partial posterior fundoplication and removal of crural stiches was performed in 1 patient. Complications occurred in 13 (15%) patients. Improvement in symptoms was observed in 70 (93%) patients in early postoperative follow-up and in 59 (78%) patients in long-term follow-up. Functional results were classified as excellent in 59 (78%) patients, good in 6 (7%) patients, fair in 7 (8%) patients, and poor in 3 (4%) patients. CONCLUSIONS: Laparoscopic reoperation for failed antireflux operations is a complex procedure, but it is safe and effective in selected patients. Reoperation after a failed antireflux repair results in excellent or good functional status in a majority of patients, but these results may deteriorate over time. PMID- 25129553 TI - Pathogenic vibrios in environmental, seafood and clinical sources in Germany. AB - Bacteria of the family Vibrionaceae naturally occur in marine and estuarine environments. Only few species of Vibrionaceae are associated with human cases of gastroenteritis, ear and wound infections, caused by ingestion of seafood or contact with Vibrio containing water. Increasing consumption of seafood (fish, fishery products and shellfish) poses a possible source of Vibrio infections in Germany. Additionally, there is a growing concern that abundances of pathogenic vibrios may increase in German coastal waters as a result of e.g. climate change resulting in probably rising surface water temperatures. According to the One Health concept the VibrioNet consortium started in 2010 to investigate the occurrence and relevance of non-cholera vibrios of human concern in Germany. Vibrios from environmental, seafood and clinical sources were analyzed with the aim to find connections between different reservoirs or sources and to identify potential ways of transmission of these pathogens to assess the risk of infections associated with them. Potentially pathogenic strains mostly belong to the species Vibrio parahaemolyticus, Vibrio vulnificus and non-O1/non-O139 Vibrio cholerae. Investigations on imported seafood and mussels from primary production areas confirmed the frequent occurrence of these species. Moreover, studies of German coastal waters and sediments showed the presence and seasonality of these marine bacteria. So far the incidence of clinical cases of vibriosis in Germany is low. Between 1994 and 2013 thirteen cases of Vibrio spp. associated wound infections and/or septicaemia have been reported. However, the high prevalence of vibrios in aquatic environments and aquatic organisms is of concern and demands continued control of food and surveillance for clinical infections with pathogenic vibrios. PMID- 25129555 TI - Staphylococcus aureus isolates from chronic osteomyelitis are characterized by high host cell invasion and intracellular adaptation, but still induce inflammation. AB - Osteomyelitis is a severe inflammatory disease of the bone that is mainly caused by Staphylococcus aureus. Particularly, bone infections are difficult to treat and can develop into a chronic course with a high relapsing rate despite of antimicrobial treatments. The complex interaction of staphylococci with osseous tissue and the bacterial ability to invade host cells are thought to determine the severity of infection. Yet, defined bacterial virulence factors responsible for the pathogenesis of osteomyelitis have not been clearly identified. The aim of this study was to detect S. aureus virulence factors that are associated with osteomyelitis and contribute to a chronic course of infection. To this purpose, we collected 41 S. aureus isolates, each 11 from acute osteomyelitis (infection period less than 2 months), 10 from chronic osteomyelitis (infection period more than 12 months), 10 from sepsis and 10 from nasal colonization. All isolates were analyzed for gene expression and in functional in-vitro systems. Adhesion assays to bone matrix revealed that all isolates equally bound to matrix structures, but invasion assays in human osteoblasts showed a high invasive capacity of chronic osteomyelitis isolates. The high invasion rate could not be explained by defined adhesins, as all infecting strains expressed a multitude of adhesins that act together and determine the level of adhesion. Following host cell invasion isolates from chronic osteomyelitis induced less cytotoxicity than all other isolates and a higher percentage of Small-colony-variant (SCV)-formation, which represents an adaptation mechanism during long-term persistence. Isolates from acute and chronic osteomyelitis strongly produced biofilm and highly expressed agr and sarA that regulate secreted virulence factors and induced an inflammatory response in osteoblasts. In conclusion, chronic osteomyelitis isolates were characterized by a high host cell invasion rate, low cytotoxicity and the ability to persist and adapt within osteoblasts. Furthermore, isolates from both acute and chronic osteomyelitis strongly produced biofilm and induced high levels of host cell inflammation, which may explain tissue destruction and bone deformation observed as typical complications of long-lasting bone infections. PMID- 25129554 TI - In vitro and in vivo cell invasion and systemic spreading of Mycoplasma agalactiae in the sheep infection model. AB - Generally regarded as extracellular pathogens, molecular mechanisms of mycoplasma persistence, chronicity and disease spread are largely unknown. Mycoplasma agalactiae, an economically important pathogen of small ruminants, causes chronic infections that are difficult to eradicate. Animals continue to shed the agent for several months and even years after the initial infection, in spite of long antibiotic treatment. However, little is known about the strategies that M. agalactiae employs to survive and spread within an immunocompetent host to cause chronic disease. Here, we demonstrate for the first time its ability to invade cultured human (HeLa) and ruminant (BEND and BLF) host cells. Presence of intracellular mycoplasmas is clearly substantiated using differential immunofluorescence technique and quantitative gentamicin invasion assays. Internalized M. agalactiae could survive and exit the cells in a viable state to repopulate the extracellular environment after complete removal of extracellular bacteria with gentamicin. Furthermore, an experimental sheep intramammary infection was carried out to evaluate its systemic spread to organs and host niches distant from the site of initial infection. Positive results obtained via PCR, culture and immunohistochemistry, especially the latter depicting the presence of M. agalactiae in the cytoplasm of mammary duct epithelium and macrophages, clearly provide the first formal proof of M. agalactiae's capability to translocate across the mammary epithelium and systemically disseminate to distant inner organs. Altogether, the findings of these in vitro and in vivo studies indicate that M. agalactiae is capable of entering host cells and this might be the strategy that it employs at a population level to ward off the host immune response and antibiotic action, and to disseminate to new and safer niches to later egress and once again proliferate upon the return of favorable conditions to cause persistent chronic infections. PMID- 25129556 TI - A motion-compensated image filter for low-dose fluoroscopy in a real-time tumor tracking radiotherapy system. AB - In the real-time tumor-tracking radiotherapy system, a surrogate fiducial marker inserted in or near the tumor is detected by fluoroscopy to realize respiratory gated radiotherapy. The imaging dose caused by fluoroscopy should be minimized. In this work, an image processing technique is proposed for tracing a moving marker in low-dose imaging. The proposed tracking technique is a combination of a motion-compensated recursive filter and template pattern matching. The proposed image filter can reduce motion artifacts resulting from the recursive process based on the determination of the region of interest for the next frame according to the current marker position in the fluoroscopic images. The effectiveness of the proposed technique and the expected clinical benefit were examined by phantom experimental studies with actual tumor trajectories generated from clinical patient data. It was demonstrated that the marker motion could be traced in low dose imaging by applying the proposed algorithm with acceptable registration error and high pattern recognition score in all trajectories, although some trajectories were not able to be tracked with the conventional spatial filters or without image filters. The positional accuracy is expected to be kept within +/-2 mm. The total computation time required to determine the marker position is a few milliseconds. The proposed image processing technique is applicable for imaging dose reduction. PMID- 25129558 TI - No sliding, no pneumothorax: thoracic ultrasound is not an all-purpose tool. PMID- 25129559 TI - West Nile virus infection and postoperative neurological symptoms: a case report and review of the literature. AB - The incidence of West Nile virus, which may cause a range of clinical presentations including subclinical infections, mild febrile illness, meningitis, or encephalitis, has increased over recent years. Rare complications, including optic neuritis, also have been reported. A patient who presented with preoperative asymptomatic West Nile virus developed fever, altered mental status and temporary vision loss after elective multilevel spine fusion surgery. PMID- 25129560 TI - Quality of life after housing first for adults with serious mental illness who have experienced chronic homelessness. AB - This 1-year longitudinal study of adults who have recently transitioned from homelessness to Permanent Supportive Housing (PSH) focuses on quality of life as a primary outcome of interest. Eighty of 103 new tenants participated in structured interviews at the time of entry into their new home and at 12-months post-housing. t-tests assessed differences in community participation and quality of life measures at the 2 time points. Mixed effects models examined the impact of community participation on quality of life. Results show that time in independent housing was significantly associated with several domains of quality of life. Symptom severity was also significantly and negatively related to quality of life domains. Community participation was significantly related to frequency of social contacts only. These findings suggest that community participation is not critical to improving quality of life, and that despite concerns that individuals may feel isolated and lonely when living independently, satisfaction with one's living situation and family relationships nevertheless improves with housing tenure. PMID- 25129557 TI - Neoadjuvant capecitabine, bevacizumab and radiotherapy for locally advanced rectal cancer: results of a single-institute Phase I study. AB - The aim of this Phase I clinical trial was to assess the feasibility and safety of capecitabine-based preoperative chemoradiotherapy (CRT) combined with bevacizumab and to determine the optimal capecitabine dose for Japanese patients with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and 29. Capecitabine was administered on weekdays concurrently with pelvic radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was initiated at 825 mg/m(2) twice daily at Dose Level 1, with a planned escalation to 900 mg/m(2) twice daily at Dose Level 2. Within 6.1-10.3 (median, 9.4) weeks after the completion of the CRT, surgery was performed. Three patients were enrolled at each dose level. Regarding the CRT-related acute toxicities, all of the adverse events were limited to Grade 1. There was no Grade 2 or greater toxicity. No patient needed attenuation or interruption of bevacizumab, capecitabine or radiation. All of the patients received the scheduled dose of CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients had a pathological complete response, and five (83.3%) patients experienced downstaging. In total, three patients (50%) developed postoperative complications. One patient developed an intrapelvic abscess and healed with incisional drainage. The other two patients healed following conservative treatment. This regimen was safely performed as preoperative CRT for Japanese patients with locally advanced rectal cancer. The recommended capecitabine dose is 900 mg/m(2) twice daily. PMID- 25129561 TI - Monitoring mood states in everyday life: a new device for patients with cerebellar ataxia. AB - Thirty patients with cerebellar ataxia and 40 healthy volunteers underwent 7 days of mood monitoring using a new device requiring a low motor load. Its convergent validity and compliance were tested. The measurements resulted consistent with validated scale scores. Patients' motor impairment did not affect the compliance. PMID- 25129562 TI - Effectiveness and clinical predictors of response to combined ECT and antipsychotic therapy in patients with treatment-resistant schizophrenia and dominant negative symptoms. AB - The effectiveness and predictors of response to electroconvulsive therapy (ECT) combined with antipsychotics (AP) in treatment-resistant schizophrenia patients with the dominance of negative symptoms (TRS-NS) have not been studied systematically so far. 29 patients aged 21-55 years diagnosed with TRS-NS underwent ECT combined with antipsychotics (ECT+AP). Prior to the ECT, the symptom profile and severity were evaluated using Positive and Negative Syndrome Scale (PANSS). Demographic and medical data was collected; ECT parameters and pharmacotherapy results were evaluated. After the combined ECT+AP therapy a significant decrease in symptom severity was found. A response to treatment was achieved by 60% of patients. The greatest reductions were obtained in general and positive PANSS subscale (median change: 11 and 7 pts.) and the smallest, but still significant, ones in negative symptoms subscale (median: 3.5 pts.). Patients who responded to ECT+AP demonstrated a significantly shorter duration of the current episode in comparison with patients who did not experience at least a 25% reduction in symptom severity (median: 4 vs. 8 months). A combination of ECT and antipsychotic therapy can provide a useful treatment option for patients with TRS-NS. The only significant predictor of response to treatment was a shorter duration of the current episode. PMID- 25129563 TI - Effects of mood state on divided attention in patients with bipolar disorder: evidence for beneficial effects of subclinical manic symptoms. AB - A relatively small number of studies have been dedicated to the differential effects of the current mood state on cognition in patients with a bipolar disorder (BD). The aim of the current study was to investigate the effect of current mood state on divided attention (DA) performance, and specifically examine possible beneficial effects of the (hypo-) manic state. Over a maximum period of 24 months, medication use, divided attention test (a subtest of the Test for Attentional Performance (TAP)) was assessed every 6 months in 189 outpatients with BD. Data were analyzed with multilevel regression analysis (i.e. linear mixed models). DA performance varied considerable over time within patients. Corrected for psychotropic medication a significant quadratic relationship between manic symptoms and DA performance was found, with mild hypomanic symptoms having a positive influence on divided attention scores and moderate to severe manic symptoms having a negative influence. No association between depressive symptoms and DA performance was found. In future research on mania and cognition as well as in the clinical practice both the beneficial and negative effects of mania should be taken into account. PMID- 25129564 TI - Adult offspring perspectives on parental hoarding behaviors. AB - Hoarding disorder (HD) is characterized by difficulty discarding unneeded items and the accumulation of items within living spaces and is associated with significant functional impairment and distress. Along with the negative impact of hoarding on the individual, HD is substantially impairing for family members, and linked to disruptions in family functioning. The present study utilized a path model analysis to examine the associations between an array of hoarding variables hypothesized to impact family functioning and parent-offspring relationships in 150 adult-aged children of hoarders who responded to online requests to participate in a research study. It was hypothesized that increased hoarding severity, decreased insight, and increased family accommodation (i.e., act of family members facilitating or assisting in hoarding behaviors) would be associated with decreased family functioning, decreased quality of parent offspring relationships, and increased offspring impairment. Results from the path model revealed that family functioning mediated the relationship between hoarding severity and parent-offspring relationship. Diminished insight in the hoarding parent (as reported by the offspring) was associated with increased familial conflict and family functioning partially mediated the relationship between insight and quality of parent-offspring relationship. Increased family accommodation was significantly associated with increased impairment (work, social, and family domains) in offspring of hoarders. PMID- 25129565 TI - Concordance of the SHEA-IDSA severity classification for Clostridium difficile infection and the ATLAS bedside scoring system in hospitalized adult patients. AB - PURPOSE: The Society for Healthcare Epidemiology of America and Infectious Diseases Society of America (SHEA-IDSA) guidelines for the treatment of Clostridium difficile infection (CDI) recommend initial treatment of CDI based on disease severity. This severity definition has not been validated or evaluated based on clinical outcomes. The ATLAS scoring system is a validated tool useful in predicting treatment response and mortality in CDI. The main purpose of this study is to evaluate the concordance of the ATLAS scoring system and the SHEA IDSA staging for CDI severity. METHODS: This was a retrospective study which included hospitalized patients with confirmed CDI. Bivariate analyses compared baseline demographics and clinical information between patients with nonsevere and severe CDI based on the SHEA-IDSA criteria for CDI severity. Kappa scores were calculated to compare the concordance of the two scoring systems in defining CDI severity. Sensitivity and specificity of the ATLAS scoring system to determine CDI severity were calculated using the SHEA-IDSA criteria as the reference standard. RESULTS: Sixty-four patients met inclusion criteria. Of those, 62.5% were classified as mild to moderate CDI, 25% were severe, uncomplicated, and 12.5% were severe, complicated based on SHEA-IDSA criteria. In the bivariate analyses, ATLAS score breakpoints of >= 4, >= 5, and >= 6 revealed moderate agreement with the SHEA-IDSA classification for severity. The sensitivities and specificities for ATLAS scores in predicting CDI severity ranged from 58.3 to 87.5, and 67.5-87.5%, respectively. CONCLUSION: The ATLAS score may be useful in evaluating CDI severity and determining drug therapy selection. PMID- 25129566 TI - A case study of enteric virus removal and insights into the associated risk of water reuse for two wastewater treatment pond systems in Bolivia. AB - Wastewater treatment ponds (WTP) are one of the most widespread treatment technologies in the world; however, the mechanisms and extent of enteric virus removal in these systems are poorly understood. Two WTP systems in Bolivia, with similar overall hydraulic retention times but different first stages of treatment, were analyzed for enteric virus removal. One system consisted of a facultative pond followed by two maturation ponds (three-pond system) and the other consisted of an upflow anaerobic sludge blanket (UASB) reactor followed by two maturation (polishing) ponds (UASB-pond system). Quantitative polymerase chain reaction with reverse transcription (RT-qPCR) was used to measure concentrations of norovirus, rotavirus, and pepper mild mottle virus, while cell culture methods were used to measure concentrations of culturable enteroviruses (EV). Limited virus removal was observed with RT-qPCR in either system; however, the three-pond system removed culturable EV with greater efficiency than the UASB pond system. The majority of viruses were not associated with particles and only a small proportion was associated with particles larger than 180 MUm; thus, it is unlikely that sedimentation is a major mechanism of virus removal. High concentrations of viruses were associated with particles between 0.45 and 180 MUm in the UASB reactor effluent, but not in the facultative pond effluent. The association of viruses with this size class of particles may explain why only minimal virus removal was observed in the UASB-pond system. Quantitative microbial risk assessment of the treated effluent for reuse for restricted irrigation indicated that the three-pond system effluent requires an additional 1 to 2-log10 reduction of viruses to achieve the WHO health target of <10(-4) disability-adjusted life years (DALYs) lost per person per year; however, the UASB-pond system effluent may require an additional 2.5- to 4.5-log10 reduction of viruses. PMID- 25129567 TI - Screen-viewing among preschoolers in childcare: a systematic review. AB - BACKGROUND: Screen-viewing is one of the most common sedentary behaviors among preschoolers. Despite the high prevalence of sedentary behaviors in childcare, little research exists on the context and/or type of activities that account for these particular behaviors. Accordingly, if the amount of screen-viewing accumulated by preschoolers in childcare is not considered, researchers may be underestimating total screen time among this population, as only a portion of their day is being captured (i.e., the home environment). This systematic review provides a synthesis of research on the levels of screen-viewing among preschool aged children (2.5-5 years) attending childcare (i.e., centre- and home-based childcare). This review also examined the correlates of screen-viewing among preschoolers in this setting. To provide additional contextual information, availability of screen activities was used to help ameliorate the understanding of preschoolers' screen-viewing behaviors in childcare. METHODS: Twelve electronic databases were searched to retrieve relevant articles for inclusion (dating from 2000 onwards). Additional studies were identified via manual searching techniques (i.e., hand searching and citation tracking). Only English, published peer-reviewed articles that examined preschoolers' screen-viewing behaviors in childcare (i.e., rates of screen-viewing and access to/opportunities for related activities) were included. No restrictions to study design were applied. RESULTS: Seventeen international studies (4 experimental; 12 cross sectional; 1 mixed-methods) published between 2004 and 2014 were examined. Of those, eight studies reported rates of screen-viewing and found that preschoolers spent approximately 0.1 to 1.3 hrs/day and 1.8 to 2.4 hrs/day engaged in this behavior in center- and home-based childcare, respectively. High staff education (negative association) and type of childcare arrangement (notably, home-based childcare in comparison to center-based childcare; positive association) were identified as two correlates in relation to preschoolers' screen-viewing in childcare. Nine studies spoke to the availability of screen-viewing activities in childcare, and found the childcare environment to be conducive to this behavior. CONCLUSIONS: Despite some variability, preschoolers appear to engage in somewhat high levels of screen-viewing while in childcare, particularly within home-based facilities. This paper also highlighted the conduciveness of the childcare environment with regard to screen-viewing among preschoolers. Additional exploration into the correlates of screen-viewing in childcare is required. (PROSPORO registration: CRD42013005552). PMID- 25129568 TI - What can providers learn from childhood body mass index trajectories: a study of a large, safety-net clinical population. AB - OBJECTIVE: To describe childhood weight gain using body mass index (BMI) z-score trajectories in a low-income urban safety-net population and identify among gender- and race/ethnicity-specific groups any trends for increased risk. METHODS: A retrospective cohort study was conducted among 2- to 12-year-old patients (2006-2013) visiting a safety-net provider. BMI z-score trajectories were calculated overall, for gender- and race/ethnicity-specific groups, and for peak BMI percentile subgroups to describe weight gain longitudinally. RESULTS: From 2006 to 2013, a total of 26,234 eligible children were followed for an average of 3.7 years. At baseline (mean age, 4.2 years), 74% of patients were at a normal weight compared to 65% at most recent observation (mean age, 7.8 years). All gender and race/ethnicity subgroups showed increasing average BMI z-scores during childhood. Children consistently under the 50th percentile and those of white race had the most stable BMI z-score trajectories. BMI z-score increased with increasing age in all subgroups. Hispanic boys and black girls had the most significant increase in BMI z-score during this observation period. Children observed in early childhood and whose BMI exceeded the 95th percentile at any time were often already overweight (20%) or obese (36%) by 3 years of age. CONCLUSIONS: The entire population demonstrated an upward trend in BMI z-score trajectory. This trend was most notable among black girls and Hispanic boys. Many obese children were already overweight by age 3, and persistence of obesity after 3 years of age was high, suggesting that intervention before age 3 may be essential to curbing unhealthy weight trajectories. PMID- 25129569 TI - The social construction of 'dowry deaths'. AB - The classification of cause of death is real in its consequences: for the reputation of the deceased, for her family, for those who may be implicated, and for epidemiological and social research and policies and practices that may follow from it. The study reported here refers specifically to the processes involved in classifying deaths of women from burns in India. In particular, it examines the determination of 'dowry death', a class used in India, but not in other jurisdictions. Classification of death is situated within a framework of special legal provisions intended to protect vulnerable women from dowry-related violence and abuse. The findings are based on 33 case studies tracked in hospital in real time, and interviews with 14 physicians and 14 police officers with experience of dealing with burns cases. The formal class into which any given death is allocated is shown to result from motivated accounting processes representing the interests and resources available to the doctors, victims, victim families, the victim's husband and his family, and ultimately, the police. These processes may lead to biases in research and to injustice in the treatment of victims and alleged offenders. Suggestions are made for methods of ameliorating the risks. PMID- 25129570 TI - The role of low levels of fullerene C60 nanocrystals on enhanced learning and memory of rats through persistent CaMKII activation. AB - Engineered nanomaterials are known to exhibit diverse and sometimes unexpected biological effects. Fullerene nanoparticles have been reported to specifically bind to and elicit persistent activation of hippocampal Ca(2+)/calmodulin dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine kinase central to Ca(2+) signal transduction and critical for synaptic plasticity, but the functional consequence of that modulation is unknown. Here we show that low doses of fullerene C60 nanocrystals (Nano C60), delivered through intrahippocampal infusion and without any obvious cytotoxicity in hippocampal neuronal cells, enhance the long-term potentiation (LTP) of rats. Intraperitoneal injection of 320 MUg/kg of Nano C60, once daily for 10 days, also enhanced spatial memory of rats in addition to an increase of LTP. In parallel, both the IH and IP administration of Nano C60 increased the autonomous activity and the level of threonine 286 (T286) autophosphorylation of CaMKII, enhanced post synaptic AMPA/NMDA ratio, and triggered time-dependent activation of ERK and CREB. Our results reveal a striking and highly unexpected ability of Nano C60 in positively modulating learning and memory, an effect that is most likely manifested through locking CaMKII in an active conformation, and may have significant implications for the potential therapeutic applications of fullerene C60, a classic engineered nanomaterial. PMID- 25129571 TI - The mechanism for keratinocyte detaching from pH-responsive chitosan. AB - In this study, we compared the detachment ratio of HaCaT and Hs68 cells from pH responsive chitosan surface by raising medium pH from 7.20 to 7.65 for 60 min. The detachment ratio of elongated Hs68 cells was over 75%, but that of round shaped HaCaT cells was less than 50%, even extending the incubation time to 6 h or enhancing the cytoskeletal contractile force with the Rho activator CN01. However, the addition of 2 mm of EDTA into the medium at pH 7.65 could effectively detach HaCaT cells (detachment ratio > 90%), indicating that the calcium ion played an important role in the detachment process. Therefore, the family of Ca(+2)-dependent integrin receptors was examined by RT-PCR, real-time PCR and immunocytochemistry. It was found the expression of integrin beta4 (ITGb4) was HaCaT cell-specific and the mRNA level of ITGb4 in undetached HaCaT cells was significantly higher than that in detached ones. By modulating ITGb4 activity with specific functional blocking antibody ASC-8, the detachment ratio of HaCaT cells could be increased to be greater than 85%. Conversely, the addition of the ligand of ITGb4 laminin into the culture system decreased the medium pH-induced detachment ratio for HaCaT cells, but not for Hs68 cells. Further addition of ASC-8 could rescue the effect of laminin on preventing the detachment of HaCaT cells from pH-sensitive chitosan surface. Therefore, this study demonstrated the interaction of ITGb4 and laminin played an important role in controlling the detachment of HaCaT cells on pH-responsive chitosan. PMID- 25129572 TI - Treatment of PTSD and Chronic Daily Headache. AB - OPINION STATEMENT: Posttraumatic stress disorder (PTSD) is often comorbid with chronic migraine (CM) and chronic tension-type headache (CTTH). Trauma-focused cognitive behavioral psychotherapies, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine have demonstrated efficacy in the treatment of PTSD. Amitriptyline, topiramate, sodium valproate, and botulinum toxin A are efficacious for treatment of chronic daily headache (CDH). Treatment studies on individuals with CDH and comorbid PTSD, however, are limited. As such, multiple therapeutic agents or modes of interventions typically are necessary, such that comprehensive treatment simultaneously utilizes approaches with established efficacy for each individual condition. PMID- 25129573 TI - Long-term wheel running changes on sensorimotor activity and skeletal muscle in male and female mice of accelerated senescence. AB - The senescence-accelerated mouse prone 8 (SAMP8) is considered a useful non transgenic model for studying aspects of aging. Using SAM resistant 1 (SAMR1) as controls, the long-term effects of wheel running on skeletal muscle adaptations and behavioral traits were evaluated in senescent (P8) and resistant (R1) male and female mice. Long-term wheel running (WR) led to increases in locomotor activity, benefits in sensorimotor function, and changes in body weight in a gender-dependent manner. WR increased body weight and baseline levels of locomotor activity in female mice and improved balance and strength in male mice, compared to sedentary-control mice. WR resulted in key metabolic adaptations in skeletal muscle, associated with an increased activity of the sirtuin 1-AMP activated protein kinase (AMPK)-PGC-1 alpha axis and changes in vascular endothelial growth factor A (Vegfa), glucose transporter type 4 (Glut4), and Cluster of Differentiation 36 (Cd36) gene expression. Overall, our data indicate that activity, balance, and strength decrease with age and that long-term WR may significantly improve the motor function in a mouse model of senescence in a gender-dependent manner. PMID- 25129574 TI - Are the leukocyte telomere length attrition and telomerase activity alteration potential predictor biomarkers for sporadic TAA in aged individuals? AB - A large variability in occurrence, complications, and age/gender manifestations characterizes individual susceptibility of sporadic thoracic aortic aneurysms (TAA), even in subjects with the same risk factor profiles. The reasons are poorly understood. On the other hand, TAA pathophysiology mechanisms remain unclear than those involved in abdominal aorta aneurysms. However, recent evidence is suggesting a crucial role of biological ageing in inter-individual risk variation of cardiovascular diseases, including sporadic TAA. Biological age rather than chronological age is a better predictor of vascular risk. Relevant assumptions support this concept. In confirming this evidence and our preliminary data, the mean of blood leukocyte telomere length, through use of terminal restriction fragment assay and in blood samples from sporadic TAA patients and controls, was examined. Telomerase activity was also analyzed in two groups. In addition, we verified the weight of genetic inflammatory variants and the major TAA risk factors in telomere/telomerase impairment. Aorta histopathological abnormalities and systemic inflammatory mediators were ultimately correlated with telomere/telomerase impairment. Data obtained demonstrated shorter telomeres and a reduced telomerase activity in TAA patients significantly associated with a genetic inflammatory risk profile, age, gender, smoking, hypertension, a histopathological phenotype, and higher levels of systemic inflammatory mediators than controls. In conclusion, telomere and telomerase activity's detection might be used as predictor biomarkers of sporadic TAA. Their impairment also suggests a strong role of vascular ageing in sporadic TAA, evocated by both environmental and genetic inflammatory factors. PMID- 25129575 TI - Experiences with capnography in acute care settings: a mixed-methods analysis of clinical staff. AB - PURPOSE: Although capnography is being incorporated into clinical guidelines, it is not used to its full potential. We investigated reasons for limited implementation of capnography in acute care areas and explored facilitators and barriers to its implementation. METHODS: A purposeful sample of physicians and nurses in emergency departments and intensive care units participated in semistructured interviews. Grounded theory, iterative data analysis, and the constant comparative method were used to analyze the data to inductively generate ideas and build theories. RESULTS: Nineteen providers were interviewed from 5 hospitals. Six themes were identified: variability in use of capnography among acute care units, availability and accessibility of capnography equipment, the evidence behind capnography use, the impact of capnography on patient care, personal experiences impacting use of capnography, and variable knowledge about capnography. Barriers and facilitators to use were found within each theme. CONCLUSIONS: We observed varied responsiveness to capnography and identified factors that work to foster or discourage its use. These data can guide future implementation strategies. A deliberate strategy to foster utilization, mitigate barriers, and broadly accelerate implementation has the potential to profoundly impact use of capnography in acute care areas with the goal of improving patient care. PMID- 25129576 TI - Correlation of patient-reported outcomes of sedation and sedation assessment scores in critically ill patients. AB - PURPOSE: Patient-reported outcomes (PROs) are recommended as indicators of quality in the intensive care unit. We studied the correlation between PROs of sedation quality and a universal sedation assessment scale in critically ill patients. MATERIALS AND METHODS: Twenty-nine mechanically ventilated adults admitted to a surgical/trauma or medical intensive care unit requiring continuous infusion sedation for 24 hours or more were prospectively included. Patient reported outcomes were evaluated through sedation questionnaire 24 hours post continuous infusion sedation. The primary outcome was the correlation of PROs with Sedation-Agitation Scale (SAS) scores. RESULTS: Mean (SD) SAS scores per 12 hour nursing shift for propofol (n=179), midazolam (n=42), and dexmedetomidine (n=8) were 3.78 (77), 3.31 (1.1), and 2.98 (0.76), respectively. The mean score for survey questions addressing perceptions of comfort was 5.3 (1, complete comfort; 10, not comfortable at all). Of the patients, 34%, 7%, and 52% would want more, less, or the same amount of sedation, respectively, if this situation were to arise again. Patient perception of comfort correlated with the percent time at goal SAS score; r=0.31 (P<.05). CONCLUSION: Patient-reported outcomes of sedation correlate with the percentage of time spent in the goal range of scores for a universal sedation assessment scale. These findings represent initial attempts to appreciate the patient's perspective in the management and monitoring of agitation. PMID- 25129577 TI - Aspiration pneumonia: a review of modern trends. AB - PURPOSE: The purpose was to describe aspiration pneumonia in the context of other lung infections and aspiration syndromes and to distinguish between the main scenarios commonly implied when the terms aspiration or aspiration pneumonia are used. Finally, we aim to summarize current evidence surrounding the diagnosis, microbiology, treatment, risks, and prevention of aspiration pneumonia. MATERIALS AND METHODS: Medline was searched from inception to November 2013. All descriptive or experimental studies that added to the understanding of aspiration pneumonia were reviewed. All studies that provided insight into the clinical aspiration syndromes, historical context, diagnosis, microbiology, risk factors, prevention, and treatment were summarized within the text. RESULTS: Despite the original teaching, aspiration pneumonia is difficult to distinguish from other pneumonia syndromes. The microbiology of pneumonia after a macroaspiration has changed over the last 60 years from an anaerobic infection to one of aerobic and nosocomial bacteria. Successful antibiotic therapy has been achieved with several antibiotics. Various risks for aspiration have been described leading to several proposed preventative measures. CONCLUSIONS: Aspiration pneumonia is a disease with a distinct pathophysiology. In the modern era, aspiration pneumonia is rarely solely an anaerobic infection. Antibiotic treatment is largely dependent on the clinical scenario. Several measures may help prevent aspiration pneumonia. PMID- 25129578 TI - Bacterial diversity assessment in soil of an active Brazilian copper mine using high-throughput sequencing of 16S rDNA amplicons. AB - Mining activities pose severe environmental risks worldwide, generating extreme pH conditions and high concentrations of heavy metals, which can have major impacts on the survival of organisms. In this work, pyrosequencing of the V3 region of the 16S rDNA was used to analyze the bacterial communities in soil samples from a Brazilian copper mine. For the analysis, soil samples were collected from the slopes (geotechnical structures) and the surrounding drainage of the Sossego mine (comprising the Sossego and Sequeirinho deposits). The results revealed complex bacterial diversity, and there was no influence of deposit geographic location on the composition of the communities. However, the environment type played an important role in bacterial community divergence; the composition and frequency of OTUs in the slope samples were different from those of the surrounding drainage samples, and Acidobacteria, Chloroflexi, Firmicutes, and Gammaproteobacteria were responsible for the observed difference. Chemical analysis indicated that both types of sample presented a high metal content, while the amounts of organic matter and water were higher in the surrounding drainage samples. Non-metric multidimensional scaling (N-MDS) analysis identified organic matter and water as important distinguishing factors between the bacterial communities from the two types of mine environment. Although habitat specific OTUs were found in both environments, they were more abundant in the surrounding drainage samples (around 50 %), and contributed to the higher bacterial diversity found in this habitat. The slope samples were dominated by a smaller number of phyla, especially Firmicutes. The bacterial communities from the slope and surrounding drainage samples were different in structure and composition, and the organic matter and water present in these environments contributed to the observed differences. PMID- 25129579 TI - Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder. AB - Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out. From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure. The association of trauma with telomere length was in the expected direction but not significant (B=-10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid early life trauma exposure did not confound the results. Overall, in this longitudinal study of military personnel deployed to Afghanistan we show an acceleration of ageing by trauma. However, development of PTSD symptoms was associated with telomere lengthening and reversed epigenetic ageing. These findings warrant further study of a perhaps dysfunctional compensatory cellular ageing reversal in PTSD. PMID- 25129580 TI - Darwinian medicine and psoriasis. AB - Darwinian medicine, or evolutionary medicine, regards some pathological conditions as attempts by the organism to solve a problem or develop defense mechanisms. At certain stages of human evolution, some diseases may have conferred a selective advantage. Psoriasis is a high-penetrance multigenic disorder with prevalence among whites of up to 3%. Psoriatic lesions have been linked with enhanced wound-healing qualities and greater capacity to fight infection. Leprosy, tuberculosis, and infections caused by viruses similar to human immunodeficiency virus have been postulated as environmental stressors that may have selected for psoriasis-promoting genes in some human populations. The tendency of patients with severe psoriasis to develop metabolic syndrome may reflect the body's attempt to react to environmental stresses and warning signs by triggering insulin resistance and fat storage. PMID- 25129581 TI - Editor's note. PMID- 25129582 TI - Clarity of purpose, focused attention: The essence of excellence. PMID- 25129583 TI - 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. Executive summary. PMID- 25129584 TI - Aspirin unresponsiveness predicts thrombosis in high-risk pediatric patients after cardiac surgery. AB - OBJECTIVE: Thrombosis occurs in up to 26% of patients with congenital heart disease after cardiac surgery and is associated with increased morbidity and mortality. Aspirin is commonly administered to reduce the risk of thrombosis, yet aspirin responsiveness is rarely assessed. In this study, we hypothesize that inadequate response to aspirin is associated with increased risk of thrombosis after selected congenital cardiac procedures considered to be high risk for thrombosis. METHODS: Patients undergoing high-risk congenital cardiac surgery who received postoperative aspirin (N = 95) were studied. Response to aspirin was determined using the VerifyNow system several days after administration. Patients were monitored prospectively for 30 days for the development of a thrombosis event and the relationship between aspirin unresponsiveness and a thrombosis event was determined by the Fisher exact test. RESULTS: Rate of aspirin unresponsiveness (>=550 aspirin reaction units [ARU]) was 10 of 95 (10.5%) and was highest in patients weighing less than 5 kg given 20.25 mg/d of aspirin. Thrombosis events occurred in 7 patients (7.4%). Thrombosis was observed in 6 of 10 (60%) patients who were unresponsive to aspirin, compared with 1 of 85 (1.2%) patients who were responsive to aspirin (P < .001). In 2 patients who were unresponsive to the initial aspirin dose, an increase in dose resulted in an adequate therapeutic aspirin response (ARU < 550), suggesting insufficiency rather than true resistance in a subset of patients. CONCLUSIONS: Postoperative thrombosis is associated with aspirin unresponsiveness in this patient population. In high-risk patients, monitoring of aspirin therapy and consideration of dose adjustment or alternative agents for unresponsive patients may be justified and warrants further investigation in a prospective trial. PMID- 25129586 TI - Mechanisms of tricuspid regurgitation in patients with hypoplastic left heart syndrome undergoing tricuspid valvuloplasty. AB - OBJECTIVES: Tricuspid regurgitation (TR) remains a risk factor for morbidity and mortality through staged palliation in patients with hypoplastic left heart syndrome (HLHS). Reports on the mechanisms associated with TR in patients with HLHS are limited. Thus, we sought to describe our experience with tricuspid valve (TV) repair in these patients, focusing on the mechanisms of TR and corresponding surgical techniques. METHODS: We performed a retrospective single-center review (January 2000 to December 2012) of patients with HLHS undergoing TV repair and completing Fontan circulation. We evaluated the pre- and postoperative echocardiograms, intraoperative findings, and surgical techniques used. RESULTS: A total of 53 TV repairs were performed in 35 patients with HLHS completing staged palliation. TV repairs were performed at stage II in 15, between stage II and III in 4, at stage III in 27, and after stage III in 7. The surgical techniques for valvuloplasty included annuloplasty (38%), anteroseptal (AS) commissuroplasty (66%), anterior papillary muscle repositioning (11%), multiple commissuroplasties (9%), septal-posterior commissuroplasty (9%), and fenestration closure (4%). The predominant jet of TR emanated along the AS commissure in 68% of the cases. All patients survived the procedure and were discharged. Preoperative echocardiography showed a dilated TV annulus on the lateral dimension, anteroposterior dimension, and area that was significantly reduced after TV repair (P < .0001). The preoperative mean TR, as assessed by lateral (P = .002) and anteroposterior (P = .005) vena contracta, was also significantly reduced after TV repair. TV repair did not significantly affect right ventricular systolic function immediately after surgery (P = .17) or at the most recent follow-up visit (P = .52). Patients with anterior leaflet prolapse were at increased risk of worse outcomes, including moderate or greater right ventricular dysfunction (P = .02). Patients requiring reoperation for TV repair were younger (6.3 vs 28.1 months, P < .0001) at the initial operation. One patient died of heart failure. Freedom from TV replacement and transplant-free survival were both 97% at the most recent follow-up point. CONCLUSIONS: TR in patients with HLHS commonly emanates from the AS commissure. The associated mechanisms are often annular dilatation and anterior leaflet prolapse. Preoperative anterior leaflet prolapse was associated with worse outcomes. Annuloplasty, closure of the AS commissure, and repositioning of the anterior papillary muscle are effective in addressing TR in the short- and mid-term in this challenging population. PMID- 25129589 TI - Pulmonary endarterectomy for distal chronic thromboembolic pulmonary hypertension. AB - OBJECTIVES: Chronic thromboembolic pulmonary hypertension can be cured by pulmonary endarterectomy. Operability assessment remains a major concern, because there are no well-defined criteria to discriminate proximal from distal obstructions, and surgical candidacy depends mostly on the surgeon's experience. The intraoperative classification of chronic thromboembolic pulmonary hypertension describes 4 types of lesions, based on anatomy and location. We describe our recent experience with the more distal (type 3) disease. METHODS: More than 500 pulmonary endarterectomies were performed at Foundation I.R.C.C.S. Policlinico San Matteo (Pavia, Italy). Because of recent changes in the patient population, 331 endarterectomies performed from January 2008 to December 2013 were analyzed. Two groups of patients were identified according to the intraoperative classification: proximal (type 1 and type 2 lesions, 221 patients) and distal (type 3 lesions, 110 patients). RESULTS: The number of endarterectomies for distal chronic thromboembolic pulmonary hypertension increased significantly over time (currently ~37%). Deep venous thrombosis was confirmed as a risk factor for proximal disease, whereas patients with distal obstruction had a higher prevalence of indwelling intravascular devices. Overall hospital mortality was 6.9%, with no difference in the 2 groups. Postoperative survival was excellent. In all patients, surgery was followed by a significant and sustained improvement in hemodynamic, echocardiographic, and functional parameters, with no difference between proximal and distal cases. CONCLUSIONS: Although distal chronic thromboembolic pulmonary hypertension represents the most challenging situation, the postoperative outcomes of both proximal and distal cases are excellent. The diagnosis of inoperable chronic thromboembolic pulmonary hypertension should be achieved only in experienced centers, because many patients who have been deemed inoperable might benefit from favorable surgical outcomes. PMID- 25129591 TI - Long-term outcomes after immediate aortic repair for acute type A aortic dissection complicated by coma. AB - OBJECTIVES: The management of acute type A aortic dissection complicated by coma remains controversial. We previously reported an excellent rate of recovery of consciousness provided aortic repair was performed within 5 hours of the onset of symptoms. This study evaluates the early and long-term outcomes using this approach. METHODS: Between August 2003 and July 2013, of the 241 patients with acute type A aortic dissection brought to the Japanese Red Cross Kobe Hospital and Hyogo Emergency Medical Center, 30 (12.4%) presented with coma; Glasgow Coma Scale was less than 11 on arrival. Surgery was performed in 186 patients, including 27 (14.5%) who were comatose. Twenty-four comatose patients underwent successful aortic repair immediately (immediate group). Their mean age was 71.0 +/- 11.1 years, Glasgow Coma Scale was 6.5 +/- 2.4, and prevalence of carotid dissection was 79%. For brain protection, deep hypothermia with antegrade cerebral perfusion was used, and postoperative induced hypothermia was performed. Neurologic evaluations were performed using the Glasgow Coma Scale, National Institutes of Health Stroke Scale, and modified Rankin Scale. RESULTS: In the immediate group, the time from the onset of symptoms to arrival in the operating theater was 222 +/- 86 minutes. Hospital mortality was 12.5%. Full recovery of consciousness was achieved in 79% of patients in up to 30 days. Postoperative Glasgow Coma Scale and National Institutes of Health Stroke Scale improved significantly when compared with the preoperative score (P < .05), and postoperative activities of daily living independence (modified Rankin Scale <3) was achieved in 50% of patients. The mean follow-up period was 56.5 months, and the cumulative survival was 48.2% after 10 years. Cox proportional hazards regression analysis indicated that immediate repair (hazard ratio, 4.3; P = .007) was the only significant predictor of postoperative survival over a 5-year period. CONCLUSIONS: The early and long-term outcomes as a result of immediate aortic repair for acute type A aortic dissection complicated by coma were satisfactory. PMID- 25129593 TI - Management of mitral regurgitation in Marfan syndrome: Outcomes of valve repair versus replacement and comparison with myxomatous mitral valve disease. AB - OBJECTIVES: The study objective was to evaluate patients with Marfan syndrome and mitral valve regurgitation undergoing valve repair or replacement and to compare them with patients undergoing repair for myxomatous mitral valve disease. METHODS: We reviewed the medical records of consecutive patients with Marfan syndrome treated surgically between March 17, 1960, and September 12, 2011, for mitral regurgitation and performed a subanalysis of those with repairs compared with case-matched patients with myxomatous mitral valve disease who had repairs (March 14, 1995, to July 5, 2013). RESULTS: Of 61 consecutive patients, 40 underwent mitral repair and 21 underwent mitral replacement (mean [standard deviation] age, 40 [18] vs 31 [19] years; P = .09). Concomitant aortic surgery was performed to a similar extent (repair, 45% [18/40] vs replacement, 43% [9/21]; P = .87). Ten-year survival was significantly better in patients with Marfan syndrome with mitral repair than in those with replacement (80% vs 41%; P = .01). Mitral reintervention did not differ between mitral repair and replacement (cumulative risk of reoperation, 27% vs 15%; P = .64). In the matched cohort, 10-year survival after repair was similar for patients with Marfan syndrome and myxomatous mitral disease (84% vs 78%; P = .63), as was cumulative risk of reoperation (17% vs 12%; P = .61). CONCLUSIONS: Patients with Marfan syndrome and mitral regurgitation have better survival with repair than with replacement. Survival and risk of reoperation for patients with Marfan syndrome were similar to those for patients with myxomatous mitral disease. These results support the use of mitral valve repair in patients with Marfan syndrome and moderate or more mitral regurgitation, including those having composite replacement of the aortic root. PMID- 25129595 TI - Topical vancomycin in combination with perioperative antibiotics and tight glycemic control helps to eliminate sternal wound infections. AB - OBJECTIVE: This study was undertaken to determine whether topical vancomycin would further reduce the incidence of sternal infections in the presence of perioperative antibiotics and tight glycemic control. METHODS: A total of 1075 consecutive patients undergoing cardiac surgery from December 2007 to August 2013 receiving topical vancomycin (2.5 g in 2 mL of normal saline) applied as a slurry to the cut edges of the sternum were compared with 2190 patients from December 2003 to November 2007 who did not receive topical vancomycin. All patients received perioperative antibiotics (cefazolin 2 g intravenously every 8 hours and vancomycin 1 g intravenously every 12 hours) on induction of anesthetic and continuing for 48 hours; and intravenous insulin infusions to maintain serum blood glucose level between 120 and 180 mg/dL. RESULTS: Patients receiving topical vancomycin had less superficial sternal infections (0% vs 1.6%; P < .0001), deep sternal infections (0% vs 0.7%; P = .005), any type of sternal infection (0% vs 2.2%; P < .0001) and significantly less sternal infections of any type in patients with diabetes mellitus (0% vs 3.3%; P = .0004). CONCLUSIONS: Topical vancomycin applied to the sternal edges, in conjunction with perioperative antibiotics and tight glycemic control, helps to eliminate wound infections in cardiac surgical patients. PMID- 25129597 TI - Circulating tumor cells from a 4-dimensional lung cancer model are resistant to cisplatin. AB - OBJECTIVE: To determine the effect of cisplatin on circulatory tumor cells (CTC) and tumor nodules in a four-dimensional (4D) lung cancer model. METHODS: CTCs from the 4D model seeded with H1299, A549, or H460 and respective cells that were grown under two-dimensional conditions in a Petri dish were treated with 50 MUM cisplatin for 24 and 48 hours and cell viability was determined. The lung nodules in the 4D model were then treated with different continuous or intermittent doses of cisplatin and the nodule size, the number of CTCs, and the level of matrix metalloproteinase (MMP) were determined. RESULTS: Cisplatin led to a significant decrease in the viability of tumor cells grown under 2D conditions (P < .01) but not in CTCs from the 4D model after both 24 hours and 48 hours. Cisplatin led to regression of tumor nodules with both the continuous and intermittent treatments. Moreover, there was a significantly higher number of CTCs per tumor area (P < .05) and MMP-2 production per tumor area (P = .007) for all human lung cancer cell lines grown in the 4D model when treated with cisplatin. CONCLUSIONS: The 4D lung cancer model allows for the isolation of CTCs that are resistant to cisplatin treatment. The model may allow us to better understand the biology of cisplatin resistance. PMID- 25129599 TI - Quantitative analysis of exhaled carbonyl compounds distinguishes benign from malignant pulmonary disease. AB - OBJECTIVES: The analysis of exhaled breath is a promising noninvasive tool for the diagnosis of lung cancer, but its clinical relevance has yet to be established. We report the analysis of exhaled volatile carbonyl compounds for the identification of specific carbonyl cancer markers to differentiate benign pulmonary disease from early-stage lung cancer and to compare its diagnostic accuracy with positron emission tomography (PET) scans. METHODS: Aminooxy-coated silicon microchips were used for the selective capture of exhaled carbonyls by an oximation reaction. Breath samples were collected then directed through the silicon chips by applying a vacuum. Carbonyl adducts were analyzed by Fourier transform mass spectrometry. Eighty-eight control subjects, 107 patients with lung cancer (64 stage 0, I, or II), 40 patients with benign pulmonary disease, and 7 patients with a solitary pulmonary metastasis participated. Analysis of cancer markers was performed blinded to the pathologic results. RESULTS: Four carbonyls were defined as cancer markers with significantly higher concentrations in patients with lung cancer. The number of increased cancer markers distinguished benign disease from both early and stage III and IV lung cancer. For early-stage disease, defining greater than 2 increased markers as diagnostic of lung cancer resulted in 83% sensitivity and 74% specificity. PET scans for this same cohort resulted in 90% sensitivity but only 39% specificity. Markers normalized for 3 of the 4 markers after resection of the lung cancer. CONCLUSIONS: Analysis of specific exhaled carbonyls can differentiate early lung cancer from benign pulmonary disease. Breath analysis was more specific than PET for a lung cancer diagnosis. Judicious use of these data may expedite the care of patients with lung cancer. PMID- 25129601 TI - Energy loss, a novel biomechanical parameter, correlates with aortic aneurysm size and histopathologic findings. AB - OBJECTIVE: Energy loss is a biomechanical parameter that represents the relative amount of energy absorbed by the aorta during the cardiac cycle. We aimed to correlate energy loss with ascending aortic aneurysm size and histopathologic findings to elucidate the pathophysiology of aneurysm complications. METHODS: Aneurysmal ascending aortic specimens were obtained during surgery. Control specimens were obtained from autopsy and organ donors. Biaxial tensile tests were performed on the 4 quadrants of the aortic ring. Energy loss was calculated using the integral of the stress-strain curve during loading and unloading. It was compared with the size and the traditional biomechanical parameter, stiffness (apparent modulus of elasticity). Elastin, collagen, and mucopolysaccharide content were quantified using Movat pentachrome staining of histology slides. RESULTS: A total of 41 aortas were collected (34 aneurysmal, 7 control). The aneurysms exhibited increased stiffness (P < .0001) and energy loss (P < .0001) compared with the controls. Energy loss correlated significantly with aortic size (P < .0001, r(2) = .60). A hinge point was noted at a diameter of 5.5 cm, after which energy loss increased rapidly. The relationship between energy loss and size became strongly linear once the size was indexed to the body surface area (P < .0001, r(2) = .78). Energy loss correlated with the histopathologic findings, especially the collagen/elastin ratio (P = .0002, r(2) = .49). High energy loss distinguished patients with pathologic histologic findings from others with similar diameters. CONCLUSIONS: As ascending aortas dilate, they exhibit greater energy loss that rapidly increases after 5.5 cm. This mirrors the increase in complications at this size. Energy loss correlates with imbalances in elastin and collagen composition, suggesting a measurable link between the histopathologic features and mechanical function. PMID- 25129605 TI - Outcomes after implantation of partial-support left ventricular assist devices in inotropic-dependent patients: Do we still need full-support assist devices? AB - OBJECTIVES: Partial-support left ventricular assist devices (LVADs) represent a novel strategy for heart failure treatment. The Synergy Pocket Micro-pump (HeartWare Inc, Framingham, Mass), the smallest surgically implanted long-term LVAD, provides partial flow up to 4.25 L/min and was primarily designed for "less sick" patients with severe heart failure. This device is implanted minimally invasively without sternotomy or cardiopulmonary bypass. Early implantation in patients with Interagency Registry for Mechanically Assisted Circulatory Support class 4 and higher was shown to be feasible and associated with significantly improved hemodynamics and quality of life. The aim of this study was to present our experience with implementation of long-term partial circulatory support as a bridge to transplantation in patients with more advanced heart failure who were dependent preoperatively on inotropic support or intra-aortic balloon pump. METHODS: In this observational study, only inotropic or intra-aortic balloon pump dependent patients with end-stage heart failure were included (n = 12). These patients underwent Synergy device implantation between February 2012 and August 2013. RESULTS: The mean preoperative Interagency Registry for Mechanically Assisted Circulatory Support class was 2.17 +/- 0.84 (class 1, 25%; class 2, 33%; class 3, 42%). The mean age was 46 +/- 15 years, and 33% were female. Preoperatively, 4 patients (33%) had at least 1 previous sternotomy, 3 patients (25%) were supported with a balloon pump, 1 patient (8%) had a previous full support LVAD, and 4 patients (33%) had cerebrovascular events in the past. After device implantation, there were no right ventricular failures, device-related infections, hemorrhagic strokes, arterial or venous thromboembolisms, or worsenings of aortic and mitral regurgitation observed over the follow-up. The mean follow up was 174 +/- 171 days (range, 5-764 days; cumulative, 3199 days). One patient (8%) died, 3 patients (25%) successfully underwent transplantation, 1 device (8%) was explanted after myocardial recovery, and 5 patients (42%) are still on ongoing support. Two patients (17%) were upgraded to a full-support LVAD after 65 days of mean support. A total of 11 of 12 patients (92%) were discharged from the hospital and are presently alive. Left ventricular end-diastolic diameter was significantly reduced 3 months after device implantation. CONCLUSIONS: Partial LVAD support may be clinically efficacious in inotropic and intra-aortic balloon pump-dependent patients. On the basis of our experience and evidence of previous research, such patients may benefit from minimally invasive access, no need for sternotomy and cardiopulmonary bypass, a short implantation time, an easy exchange if necessary, and a lower risk of subsequent heart transplantation. Because the implantation is performed without sternotomy, device upgrade is feasible with a comparatively low operative risk and good clinical outcome. Our preliminary results show that partial-support devices may have the potential to replace full-support LVADs in the near future. PMID- 25129603 TI - Tissue-engineered, hydrogel-based endothelial progenitor cell therapy robustly revascularizes ischemic myocardium and preserves ventricular function. AB - OBJECTIVES: Cell-based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to low cell retention (<1%) and dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells at high cell dosage. METHODS: Endothelial progenitor cells were isolated from Wistar rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (left anterior descending ligation) for 4 weeks. Intramyocardial cell injection (2 * 10(6) endothelial progenitor cells), empty fibrin, and isolated left anterior descending ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial progenitor cell migration was analyzed by using endothelial progenitor cells from transgenic enhanced green fluorescent protein(+) rodents. RESULTS: Endothelial progenitor cells demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-week implants demonstrated significant migration of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells from the fibrin matrix to the infarcted myocardium compared with intramyocardial cell injection (28 +/- 12.3 cells/high power field vs 2.4 +/- 2.1 cells/high power field, P = .0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present after endothelial progenitor cell-hydrogel therapy compared with control. CONCLUSIONS: We present a tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function. PMID- 25129607 TI - Functional evaluation of human donation after cardiac death donor hearts using a continuous isolated myocardial perfusion technique: Potential for expansion of the cardiac donor population. AB - OBJECTIVE: To investigate the resuscitation potential and contractile function in adult human donation after cardiac death (DCD) hearts by ex vivo perfusion. METHODS: With institutional review board approval and under the DCD protocol at the University of Wisconsin (UW) Organ Procurement Organization, 5 brain dead (BD) and 5 DCD donor hearts were evaluated. All BD hearts were declined for clinical transplantation because of coronary artery disease, advanced age, or social history. All hearts were preserved by flushing and cold storage with UW solution. By using our ex vivo perfusion system, the left ventricular end systolic pressure-volume relationship (LV-ESPVR) was assessed for 2 hours of oxygenated blood reperfusion. RESULTS: All BD (n = 5) and 4 DCD hearts were successfully resuscitated. One DCD heart was unable to be resuscitated due to prolonged warm ischemic time (WIT; 174 minutes). Mean WIT for resuscitated DCD hearts (from extubation to flushing with cold UW solution) was 34 +/- 3 minutes (range, 26 to 40 minutes); mean cold ischemic time for BD donors was 211 +/- 31 minutes compared with 177 +/- 64 minutes for DCD donors. The calculated LV-ESPVRs for BD hearts after 1 and 2 hours of reperfusion were 6.9 +/- 0.7 and 5.7 +/- 1.0 mm Hg/mL, respectively; LV-ESPVRs for DCD hearts after 1 and 2 hours of reperfusion were 5.6 +/- 1.5 (P = .45) and 3.0 +/- 0.7 mm Hg/mL (P = .07), respectively. CONCLUSIONS: We successfully resuscitated and measured ex vivo cardiac function in human DCD and BD donor hearts. Resuscitation potential in DCD hearts was achieved when the WIT was less than 40 minutes. Contractile performance in DCD hearts tended to be lower compared with BD hearts. Further investigation with longer reperfusion periods seems warranted. PMID- 25129610 TI - Synergistic proteins for the enhanced enzymatic hydrolysis of cellulose by cellulase. AB - Reducing the enzyme loadings for enzymatic saccharification of lignocellulose is required for economically feasible production of biofuels and biochemicals. One strategy is addition of small amounts of synergistic proteins to cellulase mixtures. Synergistic proteins increase the activity of cellulase without causing significant hydrolysis of cellulose. Synergistic proteins exert their activity by inducing structural modifications in cellulose. Recently, synergistic proteins from various biological sources, including bacteria, fungi, and plants, were identified based on genomic data, and their synergistic activities were investigated. Currently, an up-to-date overview of several aspects of synergistic proteins, such as their functions, action mechanisms and synergistic activity, are important for future industrial application. In this review, we summarize the current state of research on four synergistic proteins: carbohydrate-binding modules, plant expansins, expansin-like proteins, and Auxiliary Activity family 9 (formerly GH61) proteins. This review provides critical information to aid in promoting research on the development of efficient and industrially feasible synergistic proteins. PMID- 25129611 TI - Production of functional inclusion bodies in endotoxin-free Escherichia coli. AB - Escherichia coli is the workhorse for gene cloning and production of soluble recombinant proteins in both biotechnological and biomedical industries. The bacterium is also a good producer of several classes of protein-based self assembling materials such as inclusion bodies (IBs). Apart from being a relatively pure source of protein for in vitro refolding, IBs are under exploration as functional, protein-releasing materials in regenerative medicine and protein replacement therapies. Endotoxin removal is a critical step for downstream applications of therapeutic proteins. The same holds true for IBs as they are often highly contaminated with cell-wall components of the host cells. Here, we have investigated the production of IBs in a recently developed endotoxin-free E. coli strain. The characterization of IBs revealed this mutant as a very useful cell factory for the production of functional endotoxin-free IBs that are suitable for the use at biological interfaces without inducing endotoxic responses in human immune cells. PMID- 25129612 TI - Bis (aspirinato) zinc (II) complex successfully inhibits carotid arterial neointima formation after balloon-injury in rats. AB - PURPOSE: Neointima formation following angioplasty is a serious consequence of endothelial damage in arteries. Inflammatory mediators and lack of endothelial regulatory mechanisms lead to migration and proliferation of smooth-muscle cells and thus to restenosis. This study examines the effect of the novel bis (aspirinato) zinc (II) complex on neointima formation in a rat model of carotid balloon-injury. METHODS: Rats underwent balloon-injury of the right common carotid artery, then received PEG400 vehicle (untreated-group), acetylsalicylic acid (ASA-group), zinc-chloride (Zn-group) and bis (aspirinato) zinc (II) complex (Zn(ASA) 2-group) orally for 18 consecutive days. From harvested carotid arteries, histology, immunohistochemistry and mRNA expression analysis were performed. RESULTS: Compared to the untreated-group, Zn (ASA) 2-treatment significantly lowered stenosis ratio (54.0 +/- 5.8% to 25.5 +/- 3.9%) and reduced neointima/media ratio (1.5 +/- 0.2 to 0.5 +/- 0.1). Significantly higher alpha smooth muscle actin mRNA and protein expression were measured after Zn (ASA)2 and Zn-treatment in comparison with the untreated and ASA-groups while the expression of matrix-metalloproteinase-9 was significantly higher in these groups compared to Zn (ASA)2. The presence of collagen in media was significantly decreased in all treated groups. mRNA expressions of nuclear factor kappa-b, transforming growth-factor-beta and proliferating cell nuclear antigen were significantly down regulated, whereas a20 was up-regulated by Zn (ASA)2 treatment compared to the untreated and ASA-groups. CONCLUSION: This study proves the effectivity of the novel bis (aspirinato) zinc complex in reducing neointima formation and restenosis after balloon-injury and supports the hypothesis that inhibition of smooth-muscle transformation/proliferation plays a key role in the prevention of restenosis. PMID- 25129613 TI - Factors influencing eligibility for breast boost using noninvasive image-guided breast brachytherapy. AB - PURPOSE: Noninvasive image-guided breast brachytherapy (NIBB) allows for accurate targeting of the tumor bed (TB) for breast boost by using breast immobilization and image guidance. However, not all patients are candidates for this technique. METHODS: Consecutive patients treated for breast cancer were evaluated. Patients with very small breast size (cup <= A) for whom immobilization could not be achieved were treated with electrons. All others underwent simulation for NIBB boost. The rate of eligibility for NIBB, reasons for ineligibility, and related patient and anatomic factors were analyzed. RESULTS: Of 52 patients evaluated, 6 patients were ineligible for NIBB because of small breast size. Of the remaining patients who underwent simulation for NIBB boost, 33 patients (72%) were treated with NIBB. Reasons for ineligibility were the absence of identifiable TB (n = 5), inability to position patient/breast to adequately target the TB (n = 4), posterior TB location (n = 3), and discomfort during compression (n = 1). The likelihood of being eligible for NIBB boost was dependent on breast size: <=A (0%), B (50%), C (71%), D-DD (77%), and >DD (80%) (p = 0.002). The presence of surgical clips also predicted eligibility for NIBB: 79% clips vs. 45% without clips (p = 0.05). A posterior TB location was not associated with ineligibility (p = 0.2). CONCLUSIONS: NIBB boost is feasible in most patients. Patients with larger breast size are more likely to be good candidates. Posterior TB location can be challenging for NIBB, but most patients are still candidates. Surgical clips are very helpful in defining the TB and greatly increase the likelihood of eligibility for NIBB. PMID- 25129615 TI - Set-back versus buried vertical mattress suturing: results of a randomized blinded trial. AB - BACKGROUND: The set-back suture, an absorbable dermal suturing technique, purportedly improves wound eversion and cosmetic outcomes. OBJECTIVE: We sought to conduct a split-wound, prospective, randomized study to compare the cosmetic outcome and wound eversion achieved with the set-back suture and the buried vertical mattress suture (BVMS). METHODS: A total of 46 surgical elliptical wounds were randomized to subcuticular closure with the set-back suture on half and the BVMS on the other. Maximum eversion height and width were measured immediately postoperatively. At 3 months, 2 blinded observers evaluated each scar using a 7-point Likert physician global scar assessment scale. Subjects and observers also completed the validated Patient and Observer Scar Assessment Scale, where a score of 6 represents normal-appearing skin and 60 represents worst imaginable scar. RESULTS: In all, 42 subjects completed the study. The set back suture provided statistically significant wound eversion. On the Likert scale, observers rated the set-back suture side 1 point better than the BVMS side. Both patient and observer total Patient and Observer Scar Assessment Scale scores were significantly lower for the set-back suture side (subject mean 13.0 +/- 8.7 vs 16.2 +/- 12.0 [P = .039]; observer mean 24.5 +/- 10.4 vs 27.7 +/- 13.6 [P = .028], respectively). LIMITATIONS: Single institution experience and relatively short follow-up are limitations. CONCLUSION: The set-back suture provides superior wound eversion and better cosmetic outcomes than the BVMS. PMID- 25129614 TI - Soluble amyloid beta levels are elevated in the white matter of Alzheimer's patients, independent of cortical plaque severity. AB - Alzheimer's disease (AD) is the most common neurodegenerative disease and the leading cause of dementia. In addition to grey matter pathology, white matter changes are now recognized as an important pathological feature in the emergence of the disease. Despite growing recognition of the importance of white matter abnormalities in the pathogenesis of AD, the causes of white matter degeneration are still unknown. While multiple studies propose Wallerian-like degeneration as the source of white matter change, others suggest that primary white matter pathology may be due, at least in part, to other mechanisms, including local effects of toxic Abeta peptides. In the current study, we investigated levels of soluble amyloid-beta (Abeta) in white matter of AD patients (n=12) compared with controls (n=10). Fresh frozen white matter samples were obtained from anterior (Brodmann area 9) and posterior (Brodmann area 1, 2 and 3) areas of post-mortem AD and control brains. ELISA was used to examine levels of soluble Abeta -42 and Abeta -40. Total cortical neuritic plaque severity rating was derived from individual ratings in the following areas of cortex: mid-frontal, superior temporal, pre-central, inferior parietal, hippocampus (CA1), subiculum, entorhinal cortex, transentorhinal cortex, inferior temporal, amygdala and basal forebrain. Compared with controls, AD samples had higher white matter levels of both soluble Abeta -42 and Abeta -40. While no regional white matter differences were found in Abeta -40, Abeta -42 levels were higher in anterior regions than in posterior regions across both groups. After statistically controlling for total cortical neuritic plaque severity, differences in both soluble Abeta -42 and Abeta -40 between the groups remained, suggesting that white matter Abeta peptides accumulate independent of overall grey matter fibrillar amyloid pathology and are not simply a reflection of overall amyloid burden. These results shed light on one potential mechanism through which white matter degeneration may occur in AD. Given that white matter degeneration may be an early marker of disease, preceding grey matter atrophy, understanding the mechanisms and risk factors that may lead to white matter loss could help to identify those at high risk and to intervene earlier in the pathogenic process. PMID- 25129609 TI - 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. PMID- 25129616 TI - Substrate derived peptidic alpha-ketoamides as inhibitors of the malarial protease PfSUB1. AB - Peptidic alpha-ketoamides have been developed as inhibitors of the malarial protease PfSUB1. The design of inhibitors was based on the best known endogenous PfSUB1 substrate sequence, leading to compounds with low micromolar to submicromolar inhibitory activity. SAR studies were performed indicating the requirement of an aspartate mimicking the P1' substituent and optimal P1-P4 length of the non-prime part. The importance of each of the P1-P4 amino acid side chains was investigated, revealing crucial interactions and size limitations. PMID- 25129617 TI - New insights into the genetics of 5-oxoprolinase deficiency and further evidence that it is a benign biochemical condition. AB - Inherited 5-oxoprolinase (OPLAH) deficiency is a rare inborn condition characterised by 5-oxoprolinuria. To date, three OPLAH mutations have been described: p.H870Pfs in a homozygous state, which results in a truncated protein, was reported in two siblings, and two heterozygous missense changes, p.S323R and p.V1089I, were independently identified in two unrelated patients. We describe the clinical context of a young girl who manifested 5-oxoprolinuria together with dusky episodes and who is compound heterozygote for two novel OPLAH variations: p.G860R and p.D1241V. To gain insight into the aetiology of the 5-oxoprolinase deficiency, we investigated the pathogenicity of all the reported missense mutations in the OPLAH gene. A yeast in vivo growth assay revealed that only p.S323R, p.G860R and p.D1241V affected the activity of the enzyme. CONCLUSION: Taken together, this report further suggests that hereditary 5-oxoprolinase deficiency is a benign biochemical condition caused by mutations in the OPLAH gene, which are transmitted in an autosomal recessive manner, but 5-oxoprolinuria may be a chance association in other disorders. PMID- 25129618 TI - Direct observation of ferroelectric field effect and vacancy-controlled screening at the BiFeO3/LaxSr1-xMnO3 interface. AB - The development of interface-based magnetoelectric devices necessitates an understanding of polarization-mediated electronic phenomena and atomistic polarization screening mechanisms. In this work, the LSMO/BFO interface is studied on a single unit-cell level through a combination of direct order parameter mapping by scanning transmission electron microscopy and electron energy-loss spectroscopy. We demonstrate an unexpected ~5% lattice expansion for regions with negative polarization charge, with a concurrent anomalous decrease of the Mn valence and change in oxygen K-edge intensity. We interpret this behaviour as direct evidence for screening by oxygen vacancies. The vacancies are predominantly accumulated at the second atomic layer of BFO, reflecting the difference of ionic conductivity between the components. This vacancy exclusion from the interface leads to the formation of a tail-to-tail domain wall. At the same time, purely electronic screening is realized for positive polarization charge, with insignificant changes in lattice and electronic properties. These results underline the non-trivial role of electrochemical phenomena in determining the functional properties of oxide interfaces. Furthermore, these behaviours suggest that vacancy dynamics and exclusion play major roles in determining interface functionality in oxide multilayers, providing clear implications for novel functionalities in potential electronic devices. PMID- 25129620 TI - Nanoelectrical analysis of single molecules and atomic-scale materials at the solid/liquid interface. AB - Evaluating the built-in functionality of nanomaterials under practical conditions is central for their proposed integration as active components in next-generation electronics. Low-dimensional materials from single atoms to molecules have been consistently resolved and manipulated under ultrahigh vacuum at low temperatures. At room temperature, atomic-scale imaging has also been performed by probing materials at the solid/liquid interface. We exploit this electrical interface to develop a robust electronic decoupling platform that provides precise information on molecular energy levels recorded using in situ scanning tunnelling microscopy/spectroscopy with high spatial and energy resolution in a high-density liquid environment. Our experimental findings, supported by ab initio electronic structure calculations and atomic-scale molecular dynamics simulations, reveal direct mapping of single-molecule structure and resonance states at the solid/liquid interface. We further extend this approach to resolve the electronic structure of graphene monolayers at atomic length scales under standard room temperature operating conditions. PMID- 25129619 TI - Collective and individual migration following the epithelial-mesenchymal transition. AB - During cancer progression, malignant cells in the tumour invade surrounding tissues. This transformation of adherent cells to a motile phenotype has been associated with the epithelial-mesenchymal transition (EMT). Here, we show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells. Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers. We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity. Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration. The study of multicellular behaviours with single-cell resolution should enable further quantitative insights into heterogeneous tumour invasion. PMID- 25129621 TI - Absorbed doses in tissue-equivalent spheres above radioactive sources in soil. AB - Doses due to external exposure of terrestrial biota are assessed using differential air kerma from radioactive sources in soil and energy-dependent 'absorbed dose-per-air kerma' conversion factors computed for spherical tissue equivalent bodies. The presented approach allows computing average whole body absorbed dose for terrestrial organisms with body masses from 1 mg to 1,000 kg located at heights from 10 cm to 500 m above ground. Radioactive sources in soil emitting photons with energies from 10 keV to 10 MeV have been considered. Interpolation of the computed quantities over source energy, body mass, and height above ground results in plausible estimates of whole body average absorbed doses for non-human terrestrial biota from gamma-radiation emitted by any radionuclides in contaminated terrain. PMID- 25129622 TI - 13Calpha decoupling during direct observation of carbonyl resonances in solution NMR of isotopically enriched proteins. AB - Direct detection of (13)C can be advantageous when studying uniformly enriched proteins, in particular for paramagnetic proteins or when hydrogen exchange with solvent is fast. A scheme recently introduced for long-observation-window band selective homonuclear decoupling in solid state NMR, LOW-BASHD (Struppe et al. in J Magn Reson 236:89-94, 2013) is shown to be effective for (13)C(alpha) decoupling during direct (13)C' observation in solution NMR experiments too. For this purpose, adjustment of the decoupling pulse parameters and delays is demonstrated to be important for increasing spectral resolution, to reduce three spin effects, and to decrease the intensity of decoupling side-bands. LOW-BASHD then yields (13)C' line widths comparable to those obtained with the popular IPAP method, while enhancing sensitivity by ca 35 %. As a practical application of LOW BASHD decoupling, requiring quantitative intensity measurement over a wide dynamic range, the impact of lipid binding on the (13)C'-detected NCO spectrum of the intrinsically disordered protein alpha-synuclein is compared with that on the (1)H-detected (1)H-(15)N HSQC spectrum. Results confirm that synuclein's "dark state" behavior is not caused by paramagnetic relaxation or rapid hydrogen exchange. PMID- 25129623 TI - Effective strategy to assign 1H- 15N heteronuclear correlation NMR signals from lysine side-chain NH33+ groups of proteins at low temperature. AB - Recent studies have shown that lysine side-chain NH3(+) groups are excellent probes for NMR investigations of dynamics involving hydrogen bonds and ion pairs relevant to protein function. However, due to rapid hydrogen exchange, observation of (1)H-(15)N NMR cross peaks from lysine NH3(+) groups often requires use of a relatively low temperature, which renders difficulty in resonance assignment. Here we present an effective strategy to assign (1)H and (15)N resonances of NH3(+) groups at low temperatures. This strategy involves two new (1)H/(13)C/(15)N triple-resonance experiments for lysine side chains. Application to a protein-DNA complex is demonstrated. PMID- 25129624 TI - Synthesis, biological and comparative DFT studies on Ni(II) complexes of NO and NOS donor ligands. AB - Three new NOS donor ligands have been prepared by addition ethanolic suspension of 2-hydrazino-2-oxo-N-phenyl-acetamide to phenyl isocyanate (H2PAPS), phenyl isothiocyanate (H2PAPT) and benzoyl isothiocyanate (H2PABT). The Ni(II) complexes prepared from the chloride salt and characterized by conventional techniques. The isolated complexes were assigned the formulaes, [Ni2(PAPS)(H2O)2](H2O)2, [Ni(H2PAPT)Cl2(H2O)](H2O)2 and [(Ni)2(HPABT)2Cl2(H2O)2], respectively. The IR spectra of complexes shows that H2PAPS behaves as a binegative pentadentate via both CO of hydrazide moiety in keto and enol form, enolized CO of cyanate moiety and the CN (azomethine) groups of enolization. H2PAPT behaves as neutral tridentate via both CO of hydrazide moiety and CN (azomethine) group due to SH formation and finally H2PABT behaves as mononegative tetradentate via CO and enolized CO of hydrazide moiety, CO of benzoyl moiety and C=S groups. The experimental IR spectra of ligands are compared with those obtained theoretically from DFT calculations. Also, the bond lengths, bond angles, HOMO (Highest Occupied Molecular Orbitals), LUMO (Lowest Unoccupied Molecular Orbital) and dipole moments have been calculated. The calculated HOMO-LUMO energy gap reveals that charge transfer occurs within the molecule. The theoretical values of binding energies indicate the higher stability of complexes than of ligands. Also, the kinetic and thermodynamic parameters for the different thermal degradation steps of the complexes were determined by Coats-Redfern and Horowitz Metzger methods. The antibacterial activities were also tested against B. Subtilis and E. coli bacteria. The free ligands showed a higher antibacterial effect than their Ni(II) complexes. The antitumor activities of the Ligands and their Ni(II) complexes have been evaluated against liver (HePG2) and breast (MCF 7) cancer cells. All ligands were found to display cytotoxicity that are better than that of Fluorouracil (5-FU), while Ni(II) complexes show low activity. PMID- 25129625 TI - On the spectroscopic analyses of 3-(4-Hydroxy-1-methyl-2-oxo-1,2-dihydro-quinolin 3-yl)-2-nitro-3-oxo-propionic acid (HMQNP). AB - In the present work, a combined experimental and theoretical study on molecular structure and vibrational frequencies of HMQNP were reported. The FT-IR spectrum of HMQNP is recorded in the solid phase. The equilibrium geometries, harmonic vibrational frequencies, thermo-chemical parameters, total dipole moment, nuclear repulsion energy and HOMO-LUMO energies are calculated by DFT/B3LYP utilizing 6 311G(d,p) basis set. Results showed that HMQNP possesses a high dipole moment value of 9.3 Debye. HMQNP spin is doublet state which enhances frontier molecular orbitals to split into alpha (spin ?) and beta (spin ?) molecular orbitals with two different energy gaps 4.2 and 2.7 eV, respectively. HMQNP is highly recommended to be a more promising structure for many applications in optoelectronic devices such as solar cells. PMID- 25129626 TI - Synthesis, characterization and antimicrobial activities of mixed ligand transition metal complexes with isatin monohydrazone Schiff base ligands and heterocyclic nitrogen base. AB - Mixed ligand complexes of Co(II), Ni(II), Cu(II) and Zn(II) with various uninegative tridentate ligands derived from isatin monohydrazone with 2 hydroxynapthaldehyde/substituted salicylaldehyde and heterocyclic nitrogen base 8 hydroxyquinoline have been synthesized and characterized by elemental analysis, conductometric studies, magnetic susceptibility and spectroscopic techniques (IR, UV-VIS, NMR, mass and ESR). On the basis of these characterizations, it was revealed that Schiff base ligands existed as monobasic tridentate ONO bonded to metal ion through oxygen of carbonyl group, azomethine nitrogen and deprotonated hydroxyl oxygen and heterocyclic nitrogen base 8-hydroxyquinoline existed as monobasic bidentate ON bonded through oxygen of hydroxyl group and nitrogen of quinoline ring with octahedral or distorted octahedral geometry around metal ion. All the compounds have been tested in vitro against various pathogenic Gram positive bacteria, Gram negative bacteria and fungi using different concentrations (25, 50, 100, 200 MUg/mL) of ligands and their complexes. Comparative study of antimicrobial activity of ligands, and their mixed complexes indicated that complexes exhibit enhanced activity as compared to free ligands and copper(II) Cu(LIV)(Q)?H2O complex was found to be most potent antimicrobial agent. PMID- 25129627 TI - Monteggia type IV fracture in a child with radial head dislocation irreducible by closed means: a case report. AB - BACKGROUND: Fractures of the proximal third of the ulna and radius with associated anterior radial head dislocation are uncommon in children. Early recognition and appropriate management are essential to prevent long-term consequences of loss of forearm rotation, cubitus valgus, elbow instability and chronic pain. CASE PRESENTATION: We present the case of a 3-year-old Caucasian boy who attended the emergency department following an un-witnessed fall, resulting in right elbow and forearm pain, swelling and deformity. Clinical and radiological examination revealed a Monteggia type IV fracture-dislocation.The patient was treated with closed manipulation and percutaneous fixation of both bone forearm fractures with intra-medullary wires. After failed attempts at closed reduction, open reduction of the radial head was required.The block to reduction was due to a buttonholing of the radial head through the anterior joint capsule, with interposition of the capsule in the radiocapitellar joint. Subsequently, alignment was maintained with fracture healing. Follow-up at five months showed a full range of elbow movement with no adverse symptoms. CONCLUSION: Monteggia lesions of the paediatric elbow, albeit uncommon, should be considered in all forearm fractures. Accurate reduction of the radiocapitellar joint is crucial to prevent significant long-term consequences and failed closed reduction requires open reduction. Here we have described the management of a rare type IV lesion in which there was buttonholing of the radial head through the anterior capsule, causing the radiocapitellar dislocation to be irreducible (even after fixation of the radial and ulnar fractures). PMID- 25129628 TI - Snowman sign: a possible predictor of catastrophic abnormal placentation. PMID- 25129629 TI - Autonomy as self-sovereignty. AB - The concept of autonomy as self-sovereignty is developed in this essay through an examination of the thought of American transcendentalist philosophers Emerson and Thoreau. It is conceived as the quality of living in accordance with one's inner nature or genius. This conception is grounded in a transcendentalist moral anthropology that values independence, self-reliance, spirituality, and the capacity to find beauty in the world. Though still exerting considerable popular and academic influence, both the concept of autonomy as self-sovereignty and the underlying anthropology diverge in important ways from counterparts that are prominent in contemporary bioethics. Autonomy as self-sovereignty calls into question the manifold ways that patients (and citizens) are brought to heel by institutional (and political) values they do not themselves affirm. It also emphasizes the inevitable deep plurality of moral visions of health and appropriate healthcare, rejecting tendencies (strong in mainstream bioethics) to regard "health" as a univocal concept or healthcare as a basic need, to attempt to conform "reasonable" clinical decision-making to a single model, and to appoint government as a guarantor of access to healthcare or a regulator of healthcare standards. Autonomy as self-sovereignty, like its competitors, can justify itself only in question-begging terms. Still, bioethics might do well to recognize it within the mix of moral visions. PMID- 25129630 TI - Portions and sorts in Icelandic: an ERP study. AB - An ERP study investigated the processing of mass nouns used to convey 'portions' vs. 'sorts' interpretations in Icelandic. The sorts interpretation requires semantic Coercion to a count noun; the portions interpretation entails extra syntactic processing. Compared to a Neutral condition, Coercion escaped the expected penalty (N400), but the Extra Syntax condition incurred the anticipated costs (anterior negativity followed by P600). Furthermore, we examined the effects of having to revise an initial commitment to head-noun status. When another noun follows the mass noun (creating a compound), the second noun becomes the head-noun. We hypothesized, for Icelandic, there would be no effect for Extra Syntax because the compound should have been built before the second noun was encountered; by contrast, for the Coercion and Neutral conditions, processing costs would be incurred to detect and reconfigure the second noun as the head. These predictions were largely borne out (early and sustained anterior negativities). PMID- 25129631 TI - Inflectional morphology in primary progressive aphasia: an elicited production study. AB - Inflectional morphology lies at the intersection of phonology, syntax and the lexicon, three language domains that are differentially impacted in the three main variants of primary progressive aphasia (PPA). To characterize spared and impaired aspects of inflectional morphology in PPA, we elicited inflectional morphemes in 48 individuals with PPA and 13 healthy age-matched controls. We varied the factors of regularity, frequency, word class, and lexicality, and used voxel-based morphometry to identify brain regions where atrophy was predictive of deficits on particular conditions. All three PPA variants showed deficits in inflectional morphology, with the specific nature of the deficits dependent on the anatomical and linguistic features of each variant. Deficits in inflecting low-frequency irregular words were associated with semantic PPA, with lexical/semantic deficits, and with left temporal atrophy. Deficits in inflecting pseudowords were associated with non-fluent/agrammatic and logopenic variants, with phonological deficits, and with left frontal and parietal atrophy. PMID- 25129632 TI - Role of chloride ions in the promotion of auxin-induced growth of maize coleoptile segments. AB - BACKGROUND AND AIMS: The mechanism of auxin action on ion transport in growing cells has not been determined in detail. In particular, little is known about the role of chloride in the auxin-induced growth of coleoptile cells. Moreover, the data that do exist in the literature are controversial. This study describes experiments that were carried out with maize (Zea mays) coleoptile segments, this being a classical model system for studies of plant cell elongation growth. METHODS: Growth kinetics or growth and pH changes were recorded in maize coleoptiles using two independent measuring systems. The growth rate of the segments was measured simultaneously with medium pH changes. Membrane potential changes in parenchymal cells of the segments were also determined for chosen variants. The question of whether anion transport is involved in auxin-induced growth of maize coleoptile segments was primarily studied using anion channel blockers [anthracene-9-carboxylic acid (A-9-C) and 4,4'-diisothiocyanatostilbene 2,2'-disulphonic acid (DIDS)]. In addition, experiments in which KCl was replaced by KNO3 were also performed. KEY RESULTS: Both anion channel blockers, added at 0.1 mm, diminished indole-3-acetic acid (IAA)-induced elongation growth by ~30 %. Medium pH changes measured simultaneously with growth indicated that while DIDS stopped IAA-induced proton extrusion, A-9-C diminished it by only 50 %. Addition of A-9-C to medium containing 1 mm KCl did not affect the characteristic kinetics of IAA-induced membrane potential changes, while in the presence of 10 mm KCl the channel blocker stopped IAA-induced membrane hyperpolarization. Replacement of KCl with KNO3 significantly decreased IAA-induced growth and inhibited proton extrusion. In contrast to the KCl concentration, the concentration of KNO3 did not affect the growth-stimulatory effect of IAA. For comparison, the effects of the cation channel blocker tetraethylammonium chloride (TEA-Cl) on IAA-induced growth and proton extrusion were also determined. TEA-Cl, added 1 h before IAA, caused reduction of growth by 49.9 % and inhibition of proton extrusion. CONCLUSIONS: These results suggest that Cl(-) plays a role in the IAA-induced growth of maize coleoptile segments. A possible mechanism for Cl(-) uptake during IAA-induced growth is proposed in which uptake of K(+) and Cl(-) ions in concert with IAA-induced plasma membrane H(+)-ATPase activity changes the membrane potential to a value needed for turgor adjustment during the growth of maize coleoptile cells. PMID- 25129633 TI - Developmental changes in guard cell wall structure and pectin composition in the moss Funaria: implications for function and evolution of stomata. AB - BACKGROUND AND AIMS: In seed plants, the ability of guard cell walls to move is imparted by pectins. Arabinan rhamnogalacturonan I (RG1) pectins confer flexibility while unesterified homogalacturonan (HG) pectins impart rigidity. Recognized as the first extant plants with stomata, mosses are key to understanding guard cell function and evolution. Moss stomata open and close for only a short period during capsule expansion. This study examines the ultrastructure and pectin composition of guard cell walls during development in Funaria hygrometrica and relates these features to the limited movement of stomata. METHODS: Developing stomata were examined and immunogold-labelled in transmission electron microscopy using monoclonal antibodies to five pectin epitopes: LM19 (unesterified HG), LM20 (esterified HG), LM5 (galactan RG1), LM6 (arabinan RG1) and LM13 (linear arabinan RG1). Labels for pectin type were quantitated and compared across walls and stages on replicated, independent samples. KEY RESULTS: Walls were four times thinner before pore formation than in mature stomata. When stomata opened and closed, guard cell walls were thin and pectinaceous before the striated internal and thickest layer was deposited. Unesterified HG localized strongly in early layers but weakly in the thick internal layer. Labelling was weak for esterified HG, absent for galactan RG1 and strong for arabinan RG1. Linear arabinan RG1 is the only pectin that exclusively labelled guard cell walls. Pectin content decreased but the proportion of HG to arabinans changed only slightly. CONCLUSIONS: This is the first study to demonstrate changes in pectin composition during stomatal development in any plant. Movement of Funaria stomata coincides with capsule expansion before layering of guard cell walls is complete. Changes in wall architecture coupled with a decrease in total pectin may be responsible for the inability of mature stomata to move. Specialization of guard cells in mosses involves the addition of linear arabinans. PMID- 25129635 TI - Trends in analyzing emerging drugs of abuse--from seized samples to body samples. AB - This article summarizes the current status of and new trends of analytical approaches in the field of forensic/clinical toxicology for analyzing emerging drugs of abuse. Instruments and devices used for compound identification will be presented as well as types of biosample used to check for drug intake. Finally, a new and promising strategy will be presented, which allows to monitor the consumption of emerging drugs of abuse without using real body samples. PMID- 25129634 TI - Quantification of cocaine and metabolites in exhaled breath by liquid chromatography-high-resolution mass spectrometry following controlled administration of intravenous cocaine. AB - Breath has been investigated as an alternative matrix for detecting recent cocaine intake; however, there are no controlled cocaine administration studies that investigated the drug's disposition into breath. Breath was collected from 10 healthy adult cocaine users by asking them to breathe into a SensAbues device for 3 min before and up to 22 h following 25 mg intravenous (IV) cocaine dosing on days 1, 5, and 10, and assayed with a validated liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to quantify breath cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), and norcocaine. The assay was linear from 25 to 1,000 pg/filter, extraction efficiencies were 83.6-126%, intra- and inter-assay imprecision was <10.6%, and bias was between -8.5 and 16.8%. No endogenous or exogenous interferences were observed for more than 75 tested. Analytes were generally stable under short-term storage conditions. Ion suppression was less than 46%. Of breath specimens collected after controlled cocaine administration, 2.6% were positive for cocaine (26.1-66 pg/filter, 1-9.5 h), 0.72% BE (83.3-151 pg/filter, 6.5-12.5 h), and 0.72% EME (50-69.1 pg/filter, 6.5-12.5 h); norcocaine was not detected. Methanolic extraction of the devices themselves, after filters were removed, yielded 19.2% positive cocaine tests (25.2-36.4 pg/device, 10 min-22 h) and 4.3% positive BE tests (26.4-93.7 pg/device, 10 min-22 h), explaining differences between the two extraction techniques. These results suggest that the device reflects the drug in oral fluid as well as lung microparticles, while the filter reflects only drug-laden microparticles. A sensitive and specific method for cocaine, BE, EME, and norcocaine quantification in breath was developed and validated. Cocaine in breath identifies recent cocaine ingestion, but its absence does not preclude recent use. PMID- 25129636 TI - Reduced oocyte and embryo quality in response to elevated non-esterified fatty acid concentrations: a possible pathway to subfertility? AB - Reproductive performance is increasingly considered as a 'barometer' of general well-being of the mother. A normal maternal 'metabolic health' status is essential to safeguard successful ovulation, conception and further embryo development. When alterations in serum metabolites are reflected in the oocyte and embryonic micro-environment, these metabolic changes can affect follicle health, oocyte development and even subsequent embryo physiology. The search continues for signals that may be critically affecting the early developmental stages in life. Years of expertise in animal in vitro embryo culture models contribute to the awareness on the influence of elevated non-esterified fatty acid (NEFA) concentrations on follicle cells, oocyte and embryo quality. High NEFA concentrations in the blood are known to alter the follicular micro environment. The latter alterations in NEFA concentrations have been associated with a disappointing fertility outcome through disabled ovarian cell function and reduced oocyte's developmental competence. Even more, elevated NEFA concentrations during bovine oocyte maturation influence the subsequent embryo characteristics. This review provides a cross-species overview on the consequences of elevated NEFA concentrations, originating from maternal lipolytic conditions, on female fertility, with particular focus on the early stages in life. Thereby, we will describe to what extent elevated serum NEFA concentrations are a potential threat around the period of conception. PMID- 25129637 TI - Protein supplementation during a short-interval prostaglandin-based protocol for timed AI in sheep. AB - The aim of this experiment was to improve the reproductive performance of a short interval prostaglandin (PG)-based protocol for timed artificial insemination in sheep, using a short-term nutritional treatment. During the breeding season (March-April), 132 multiparous and 61 nulliparous Corriedale ewes grazing natural pastures (600 kg DM/ha, 8.5% CP), were allocated to two groups: 1, Control group (n=100) two injections of D-Cloprostenol (75 MUg per dose, 7d apart: Synchrovine((r)) protocol); and 2, Supplemented group (n=93) ewes in which stage of the oestrous cycle was synchronised with Synchrovine((r)) protocol plus focus feeding of a protein supplement (33.8% CP) between PG doses (Day -7 to -2). Cervical AI was performed at fixed time (Day 0), 46 +/- 1.0 h after the second PG injection using 150 million sperm per ewe. Ovulation rate (Day 10), pregnancy rate, prolificacy and fecundity at Day 69 were evaluated by ultrasonography. Ovulation rate at Day 10 (1.20 +/- 0.05 vs. 1.22 +/- 0.05), pregnancy (46 +/- 0.05 vs. 56 +/- 0.05), prolificacy (1.09 +/- 0.04 vs. 1.06 +/- 0.05), and fecundity (0.49 +/- 0.06 vs. 0.59 +/- 0.06) at Day 69, were similar between groups (P>0.05; Control and Supplemented group respectively). It is concluded that focus feeding for 6d with protein supplementation during a short-interval PG based protocol (Synchrovine((r))) did not improve the reproductive outcome associated with this protocol. PMID- 25129638 TI - Starting Ovsynch protocol on day 6 of first postpartum estrous cycle increased fertility in dairy cows by affecting ovarian response during heat stress. AB - The objective was to compare fertility in cows using an Ovsynch protocol starting on day 6 of first postpartum estrous cycle with an Ovsynch protocol initiated at random stages of the estrous cycle during heat stress (temperature-humidity index (THI)=77-83). Cows (n=459) at the beginning of the lactation period were randomly assigned to time-of-ovulation synchronization treatments: (1) control, Ovsynch (first GnRH treatment, PGF2alpha treatment 7 days later, second GnRH treatment 56 h later, and TAI 16 h later), initiated at random stages of the estrous cycle (40 +/- 2 days postpartum, n=224) and (2) Ovsynch initiated on day 6 of first postpartum estrous cycle (estrus=day 0) based on detection of the first estrus after day 30 postpartum (O6, 35 +/- 2 postpartum, n=235). Statistical analyses were conducted using SAS. The percentage of cows responding to the initial GnRH injection using the Ovsynch protocol was greater with the O6 treatment compared to the control treatment (60.4% compared with 52.6%). The percentage of cows having a corpus luteum (CL) on the day of the PGF2alpha injection was not different among treatments (control=87.0% and O6=90.2%, respectively). Also more cows in the O6 treatment group responded to the second GnRH injection of the Ovsynch protocol compared with control treatments (82.5% compared with 75.8%). Treatment affected the percentage of cows diagnosed pregnant at 32 +/- 0.7 days and 60 +/- 3 days after the resynchronized timing of AI but pregnancy losses (5.3% compared with 6.8%) did not differ between treatment groups. It is concluded that initiating the Ovsynch protocol 6 days after estrus during the first 40 days postpartum resulted in a greater pregnancy rate at the synchronized estrus and increased fertility compared with control cows during heat stress. PMID- 25129639 TI - Impact of persistent smoking on long-term outcomes in patients with nonvalvular atrial fibrillation. AB - BACKGROUND: Although smoking is a risk factor for cardiovascular diseases, little is known about the impact of smoking on long-term outcomes in patients with atrial fibrillation (AF). METHODS: In 426 consecutive patients with nonvalvular AF (mean age, 66 years; 307 men; mean follow-up, 5.8+/-3.2 years), clinical variables including smoking status, CHADS2, and CHA2DS2-VASc score, incidences of cardiovascular events (stroke, myocardial infarction, or admission for heart failure), bleeding, and mortality were determined. RESULTS: Incidences of intracranial bleeding (0.7% vs 0.1%/year, p<0.01), all-cause mortality (4.9% vs 2.6%/year, p<0.01), and death from stroke (0.8% vs 0.2%/year, p<0.05) were higher in patients with history of smoking than in those without it. Incidence of intracranial bleeding was significantly higher in persistent smokers than in non persistent smokers (1.2% vs 0.2%/year, p<0.01). History of smoking predicted all cause mortality [hazard ratio (HR), 2.7; 95% confidence interval (CI), 1.7-4.5; p<0.01] and death from stroke (HR 4.7; 95% CI 1.0-22.3; p<0.05) independent of age, antithrombotic treatment, CHADS2, and CHA2DS2-VASc score. Persistent smoking predicted intracranial bleeding (HR 4.4; 95% CI 1.1-17.6; p<0.05) independent of age and antithrombotic treatment. CONCLUSIONS: Smoking status, independent of age, antithrombotic treatment, and clinical risk factors, predicted long-term adverse outcomes including bleeding events in patients with nonvalvular AF. There might be an obvious impact of persistent smoking on intracranial bleeding. PMID- 25129640 TI - Multi-pore carbon phase plate for phase-contrast transmission electron microscopy. AB - A new fabrication method of carbon based phase plates for phase-contrast transmission electron microscopy is presented. This method utilizes colloidal masks to produce pores as well as disks on thin carbon membranes for phase modulation. Since no serial process is involved, carbon phase plate membranes containing hundreds of pores can be mass-produced on a large scale, which allows "disposal" of contaminated or degraded phase modulating objects after use. Due to the spherical shape of the mask colloid particles, the produced pores are perfectly circular. The pore size and distribution can be easily tuned by the mask colloid size and deposition condition. By using the stencil method, disk type phase plates can also be fabricated on a pore type phase plate. Both pore and disk type phase plates were tested by measuring amorphous samples and confirmed to convert the sinus phase contrast transfer function to the cosine shape. PMID- 25129641 TI - Variability of Bacillus thuringiensis strains by ERIC-PCR and biofilm formation. AB - Bacillus thuringiensis (Bt) is a soil-dwelling bacterium of great interest for agronomical research because of its use as biological pesticide. There are some limitations regarding the subspecies classification. Phenotyping and genotyping studies are important to ascertain its variability. The diversity of 40 environmental strains, isolated from different regions in Mexico, was analyzed by ERIC-PCR and the ability of biofilm formation. Thirty-nine different fingerprinting patterns revealed enough data to discriminate among the 40 strains. A total of 24 polymorphic fragments with sizes between 139 and 1,468 bp were amplified. Almost all (95 %) strains showed biofilm formation after 96 h of incubation. At 96 h of incubation the biofilm-forming strains from the CINVESTAV collection showed a more heterogeneous ability as biofilms producers. Results showed a large intra-species genomic variability in Bt. However, some strains could be correlated as they were found within clusters depending on the location of isolation. PMID- 25129642 TI - An unusual presentation of dermatophytosis in a premature infant. PMID- 25129643 TI - Physical activity modifies the associations between genetic variants and blood pressure in European adolescents. AB - We hypothesized that physical activity and sedentary behavior could modify the associations between known genetic variants blood pressure-associated genes in European adolescents. Meeting current physical activity recommendations (>= 60 minutes/day) was able attenuate the deleterious effect of the NOS3 rs3918227 polymorphism on systolic blood pressure in European adolescents. PMID- 25129644 TI - A photoacoustic image reconstruction method using total variation and nonconvex optimization. AB - BACKGROUND: In photoacoustic imaging (PAI), the reduction of scanning time is a major concern for PAI in practice. A popular strategy is to reconstruct the image from the sparse-view sampling data. However, the insufficient data leads to reconstruction quality deteriorating. Therefore, it is very important to enhance the quality of the sparse-view reconstructed images. METHOD: In this paper, we proposed a joint total variation and Lp-norm (TV-Lp) based image reconstruction algorithm for PAI. In this algorithm, the reconstructed image is updated by calculating its total variation value and Lp-norm value. Along with the iteration, an operator-splitting framework is utilized to reduce the computational cost and the Barzilai-Borwein step size selection method is adopted to obtain the faster convergence. RESULTS AND CONCLUSION: Through the numerical simulation, the proposed algorithm is validated and compared with other widely used PAI reconstruction algorithms. It is revealed in the simulation result that the proposed algorithm may be more accurate than the other algorithms. Moreover, the computational cost, the convergence, the robustness to noises and the tunable parameters of the algorithm are all discussed respectively. We also implement the TV-Lp algorithm in the in-vitro experiments to verify its performance in practice. Through the numerical simulations and in-vitro experiments, it is demonstrated that the proposed algorithm enhances the quality of the reconstructed images with faster calculation speed and convergence. PMID- 25129645 TI - Solubility and release modulation effect of sulfamerazine ternary complexes with cyclodextrins and meglumine. AB - This study investigated the effect on solubility and release of ternary complexes of sulfamerazine (SMR) with beta-(betaCD), methyl-(MbetaCD) and hydroxypropyl beta-cyclodextrin (HPbetaCD) using meglumine (MEG) as the ternary component. The combination of MEG with MbetaCD resulted the best approach, with an increased effect (29-fold) of the aqueous solubility of SMR. The mode of inclusion was supported by 2D NMR, which indicated that real ternary complexes were formed between SMR, MEG and MbetaCD or HPbetaCD. Solid state analysis was performed using Fourier-transform infrared spectroscopy (FT IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD), which demonstrated that different interactions occurred among SMR, MEG and MbetaCD or HPbetaCD in the ternary lyophilized systems. The ternary complexes with betaCD and MbetaCD produced an additional retention effect on the release of SMR compared to the corresponding binary complexes, implying that they were clearly superior in terms of solubility and release modulation. PMID- 25129646 TI - Localized Pulmonary Edema in the Middle and Inferior Lobes of the Right Lung after One-lung Ventilation for Minimally Invasive Mitral Valve Surgery. PMID- 25129647 TI - Pancreatic arteriovenous malformation. PMID- 25129648 TI - High throughput screening of enzyme activity with mass spectrometry imaging. AB - Mass spectrometry imaging (MSI) has found a diversity of applications ranging from localizing metabolites and proteins in tissues to investigating microbial interactions, and as a result is perhaps the fastest growing subfield of mass spectrometry. Advances in surface mass spectrometry technologies are equally applicable to the analysis of arrayed samples. One promising field in which this capacity has been leveraged is the high-throughput analysis of enzyme activity, an important step in the development of a wide range of biotechnologies. This review article describes several emerging approaches that seek to improve the quality and scope of this application of MSI. PMID- 25129649 TI - Alpha linolenic acid and oleic acid additively down-regulate malignant potential and positively cross-regulate AMPK/S6 axis in OE19 and OE33 esophageal cancer cells. AB - OBJECTIVE: Both oleic acid (OA) and alpha-linolenic acid (ALA) have been proposed to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that OA and/or ALA suppresses to the development of esophageal cancer has not been studied. Also, no previous studies have evaluated how OA and/or ALA regulates malignant potential (cell proliferation, migration, colony formation and adhesion) and intracellular signaling pathways, and whether their effects might be synergistic and/or additive in esophageal cancer cells has not yet been elucidated. MATERIALS/METHODS: We conducted in vitro studies and evaluated whether OA and ALA alone or in combination may regulate malignant potential in OE19 and OE33 esophageal cancer cell lines. RESULTS: Both OA and ALA significantly down-regulated cell proliferation, adhesion and/or migration. OA and/or ALA did not change the number of colonies but decrease colony sizes when compared to control. Also, we observed that OA and/or ALA positively cross-regulates the expression levels of AMPK/S6 axis. Moreover, OA and ALA up-regulated tumor suppressor genes (p53, p21, and p27) and these effects are abolished by AMPK siRNA administration. Importantly, we observed that these effects are additively regulated by OA and ALA in combination when compared to control in OE19 and OE33 esophageal cancer cell lines. CONCLUSIONS: Our novel mechanistic studies provide evidence for an important role for OA and ALA in esophageal cancer, and suggest that OA and/or ALA might be useful agents in the management or chemoprevention of esophageal cancer. PMID- 25129650 TI - Thyroid core needle biopsy: taking stock of the situation. AB - Recently, the microhistologic evaluation by core needle biopsy (CNB) has been reported as high accurate to diagnose thyroid nodules with previous indeterminate or not adequate fine-needle aspiration cytology. In addition, sparse data have been reported regarding the use of CNB in other conditions. Aim of this review was to furnish the state of the art of this topic by summarizing published data about the diagnostic performance of CNB in thyroid lesions, and provide an easy to use reference for clinical practice. Sources encompass studies published through May 2014. Original articles were investigated and following specific aspects were discussed: 1. The "large" needle biopsy in 90's; 2. Complications by and patient's comfort with thyroid CNB; 3. Advantages provided by examination of a microhistologic sample of thyroid nodule; 4. Use of CNB in thyroid nodules with previous not adequate (Thy 1/Class 1/Category I) cytology; 5. Use of CNB in thyroid neoplasms (Thy 3/Class 3/Category III-IV) cytology; 6. Use of CNB in specific ultrasonographic presentations of thyroid nodules or in patients with peculiar clinical contexts; 7. First-line approach by CNB in thyroid nodules; 8. Immunohistochemistry and molecular tests on CNB samples; and 9. Future perspective. PMID- 25129653 TI - Complete band gaps in a polyvinyl chloride (PVC) phononic plate with cross-like holes: numerical design and experimental verification. AB - In this work the existence of band gaps in a phononic polyvinyl chloride (PVC) plate with a square lattice of cross-like holes is numerically and experimentally investigated. First, a parametric analysis is carried out to find plate thickness and cross-like holes dimensions capable to nucleate complete band gaps. In this analysis the band structures of the unitary cell in the first Brillouin zone are computed by exploiting the Bloch-Floquet theorem. Next, time transient finite element analyses are performed to highlight the shielding effect of a finite dimension phononic region, formed by unitary cells arranged into four concentric square rings, on the propagation of guided waves. Finally, ultrasonic experimental tests in pitch-catch configuration across the phononic region, machined on a PVC plate, are executed and analyzed. Very good agreement between numerical and experimental results are found confirming the existence of the predicted band gaps. PMID- 25129651 TI - Growth hormone tumor histological subtypes predict response to surgical and medical therapy. AB - Growth hormone (GH) pituitary tumors are associated with significant morbidity and mortality. Current treatments, including surgery and medical therapy with somatostatin analogs (SSA), dopamine agonists and/or a GH receptor antagonist, result in disease remission in approximately half of patients. Predictors of GH tumor response to different therapies have been incompletely defined based on histologic subtype, particularly densely (DG) versus sparsely (SG) granulated adenomas. The aim of this study was to examine our own institutional experience with GH adenomas and correlate how subtype related to clinical parameters as well as response to surgery and medical therapies. A retrospective chart review of 101 acromegalic patients operated by a single neurosurgeon was performed. Clinical data were correlated with histologic subtype and disease control, as defined by IGF-1 levels, and random growth hormone levels in response to surgery and/or medical therapies. SG tumors, compared to DG, occurred in younger patients (p = 0.0010), were 3-fold larger (p = 0.0030) but showed no differences in tumor invasion characteristics (p = 0.12). DG tumors had a higher rate of remission in response to surgery compared to SG, 65.7 vs. 14.3 % (p < 0.0001), as well as to medical therapy with SSAs (68.8 % for DG vs. 28.6 % for SG tumors; p = 0.028). SG tumors not controlled with SSAs consistently responded to a switch to, or addition of, a GH receptor antagonist. Histological GH tumor subtyping implicates a different clinical phenotype and biologic behavior, and provides prognostic significance for surgical success and response to medical therapies. PMID- 25129654 TI - Altered head orientation patterns in children with idiopathic scoliosis in conditions with sensory conflict. AB - PURPOSE: Idiopathic scoliosis (IS) is the most common spinal deformity in adolescents. Defective postural equilibrium may be a contributing factor. The information of the three sensory systems combined enables the formation of a central representation of head position and body posture. Comparison of head angles of girls with and without scoliosis may result in a difference in head orientation. METHODS: 25 girls with IS and 16 girls without scoliosis (NS) between the age of 10-16 years stand in a special constructed box on a roll tilting platform (tilt -14 degrees to +14 degrees ). RESULTS: NS and IS subjects behave quite similarly if there is no sensory conflict, but if there is conflict, the differences between the two groups are greater, especially within the 13- to 14-year-old category. CONCLUSIONS: The differences between groups for different age categories suggest that the process of development of sensory integration for estimation of verticality appears to be different for girls with scoliosis. PMID- 25129652 TI - Steroid replacement in primary adrenal failure does not appear to affect circulating adipokines. AB - Despite continuous efforts for an optimal steroid replacement, recent observations suggest increased cardiometabolic risk and related mortality in primary adrenal insufficiency (PAI). Adipokines are peptides from the adipose tissue, markers of cardiometabolic dysfunction. This study was aimed to evaluate serum levels of adipokines: leptin, adiponectin, and resistin in PAI during conventional steroid substitution. The analysis comprised 63 patients (mean age 42.7 +/- 14.1 years) and 63 healthy controls. Serum adipokines, lipid profile, and plasma glucose were assessed in both cohorts. ACTH, serum insulin, HOMA-IR, DHEA-S, cortisol and 24 h urinary free cortisol were determined in PAI. Body mass composition was analyzed by Dual-Energy X-ray Absorptiometry. Mean BMI in the control group was 24.1 +/- 3.9 kg/m(2) and 23.7 +/- 3.9 kg/m(2) in the PAI cohort. Serum leptin and adiponectin levels were similar in both groups, whereas resistin appeared significantly lower among affected subjects (p = 0.0002). Its levels were weakly correlated with HOMA-IR (p = 0.048). Leptin was independently correlated with fasting insulin, HOMA-IR, BMI, and body fat (p < 0.001). At the multiple regression analysis only weight (p = 0.017), total and HDL cholesterol (p < 0.001) appeared significant predictors of adiponectin level. No adipokine correlations with serum cortisol or daily hydrocortisone dose were found. Patients receiving DHEA substitution displayed lower leptin and adiponectin levels (p < 0.05). In conclusion, our study did not provide evidence of an adverse adipokine profile in patients with PAI under conventional glucocorticoid replacement. Serum adipokines in treated PAI follow similar correlations to those reported in healthy subjects. Further prospective studies are warranted to verify and explain plausible excess of cardiovascular mortality in PAI. PMID- 25129655 TI - Volumetric three-dimensional computed tomographic evaluation of the upper airway in patients with obstructive sleep apnoea syndrome treated by maxillomandibular advancement. AB - Obstructive sleep apnoea syndrome is the periodic reduction or cessation of airflow during sleep together with daytime sleepiness. Its diagnosis requires polysomnographic evidence of 5 or more episodes of apnoea or hypopnoea/hour of sleep (apnoea/hypopnoea index, AHI). Volumetric 3-dimensional computed tomographic (CT) reconstruction enables the accurate measurement of the volume of the airway. Nasal continuous positive airway pressure (CPAP) is the conventional non-surgical treatment for patients with severe disease. Operations on the soft tissues that are currently available give success rates of only 40%-60%. Maxillomandibular advancement is currently the most effective craniofacial surgical technique for the treatment of obstructive sleep apnoea in adults. However, the appropriate distance for advancement has not been established. Expansion of the air-flow column volume did not result in an additional reduction in AHI, which raises the important issue of how much the maxillomandibular complex should be advanced to obtain an adequate reduction in AHI while avoiding the risks of overexpansion or underexpansion. We have shown that there is a significant linear relation between increased absolute upper airway volume after advancement and improvement in the AHI (p=0.013). However, increases in upper airway volume of 70% or more achieved no further reduction in the AHI, which suggests that the clinical improvement in AHI reaches a plateau, and renders further expansion unnecessary. This gives a new perspective to treatment based on the prediction of changes in volume, so the amount of sagittal advancement can be tailored in each case, which replaces the current standard of 1cm. PMID- 25129657 TI - [Effects of air pollution on mortality. Comments]. PMID- 25129658 TI - [Insulin treatment in patients over 80 years old and the risk of hypoglycemia]. PMID- 25129656 TI - Dietary fiber intake and its association with indicators of adiposity and serum biomarkers in European adolescents: the HELENA study. AB - PURPOSE: To evaluate total, energy-adjusted dietary fiber (DF), water-soluble fiber (WSF), and water-insoluble fiber (WIF) intakes in European adolescents and to investigate their association with indicators of adiposity and serum biomarkers. METHODS: This study, conducted from 2006 to 2007, included 1804 adolescents aged 12.5-17.5 years (47% males) from eight European cities completing two non-consecutive computerized 24-h dietary recalls. GLM multivariate analysis was used to investigate associations. RESULTS: Mean DF intake (20 g/day) of the sample met the European Food Safety Authority recommendation, but was below those of the World Health Organization and of the Institute of Medicine. Total DF, WSF and WIF intakes were higher in males (P < 0.001), but following energy-adjustments significantly higher intakes were observed among females (P < 0.001). Bread and cereals contributed most to total DF, WSF and WIF intakes, followed by potatoes and grains, energy-dense but low nutritious foods, fruits and vegetables. Moreover, energy-adjusted WSF and WIF were positively associated with body fat percentage (BF%), waist to height ratio and low-density lipoprotein cholesterol, while energy-adjusted WSF was inversely associated with serum fasting glucose (beta = -0. 010, P = 0.020). CONCLUSION: Total DF intakes are rather low in European adolescents. An inverse association with serum fasting glucose might indicate a possible beneficial role of DF in preventing insulin resistance and its concomitant diseases, even though DF intakes were positively associated with adolescents' BF%. Therefore, further longitudinal studies should elaborate on these potential beneficial effects of DF intake in the prevention of obesity and related chronic diseases. PMID- 25129659 TI - Structural and dynamical properties of Li+-dibenzo-18-crown-6(DB18C6) complex in pure solvents and at the aqueous-organic interface. AB - Microstructure of dibenzo-18-crown-6 (DB18C6) and DB18C6/Li(+) complex in different solvents (water, methanol, chloroform, and nitrobenzene) have been analyzed using radial distribution function (RDF), coordination number (CN), and orientation profiles, in order to identify the role of solvents on complexation of DB18C6 with Li(+), using molecular dynamics (MD) simulations. In contrast to aqueous solution of LiCl, no clear solvation pattern is found around Li(+) in the presence of DB18C6. The effect of DB18C6 has been visualized in terms of reduction in peak height and shift in peak positions of g(Li-Ow). The appearance of damped oscillations in velocity autocorrelation function (VACF) of complexed Li(+) described the high frequency motion to a "rattling" of the ion in the cage of DB18C6. The solvent-complex interaction is found to be higher for water and methanol due to hydrogen bond (HB) interactions with DB18C6. However, the stability of DB18C6/Li(+) complex is found to be almost similar for each solvent due to weak complex-solvent interactions. Further, Li(+) complex of DB18C6 at the liquid/liquid interface of two immiscible solvents confirm the high interfacial activity of DB18C6 and DB18C6/Li(+) complex. The complexed Li(+) shows higher affinity for water than organic solvents; still they remain at the interface rather than migrating toward water due to higher surface tension of water as compared to organic solvents. These simulation results shed light on the role of counter-ions and spatial orientation of species in pure and hybrid solvents in the complexation of DB18C6 with Li(+). PMID- 25129660 TI - Computational investigation of interaction of polypyrrole on the surface of single-walled carbon nanotube. AB - A density functional theory investigation of adsorption of monomer, dimer and trimer forms of pyrrole on the outer surface of zigzag (7,0) single-walled carbon nanotube (SWCNT) has been reported. Geometries of the complexes were optimized using the M06-2X functional and the 6-31G(d,p) basis set. Moreover, 6-311G(d,p), cc-pVDZ and cc-pVTZ basis sets were used for the adsorption energy calculation and such energies were corrected for the basis set superposition error. Vertical ionization potential and electron affinity of the investigated system were also computed. The interaction of polypyrrole on the SWCNT surface is characterized by the stacking interaction. Adsorption (binding) energy of pyrrole on the SWCNT surface is weak, but such energy increases with the number of monomer units in the pyrrole oligomer. In the SWCNT-pyrrole complexes, the oxidation and reduction processes will take place only at the SWCNT. The influence of larger unit on the electronic properties of the complex has been detailed. PMID- 25129661 TI - Theoretical investigation of the mechanisms and dynamics of the reaction CHF2OCF 2CHFCl+Cl. AB - The reaction of CHF2OCF2CHFCl with atomic chlorine was studied using B3LYP/6 311G(d,p), BHandHLYP/6-311G(d,p), and M06-2X/6-311G(d,p) methods and further using CCSD(T) and QCISD(T) methods. Two hydrogen abstraction channels were found for the title reaction. Dynamics calculations were followed by means of canonical variational transition state with the small-curvature tunneling correction between 220 and 2,000 K. Our rate constant k = 2.90 * 10(-15) cm(3) molecule(-1) s(-1) is in reasonable agreement with the available data (3.20 +/- 0.32) * 10( 15) cm(3) molecule(-1) s(-1) at 296 K. The three-parameter Arrhenius expression (in the unit of cm(3) molecule(-1) s(-1)) for the title reaction is given as k (T) = 1.38 * 10 (-19) T (2.57) exp (-2622.95/T). PMID- 25129662 TI - Evidence of a long C-C attractive interaction in cerussite mineral: QTAIM and ELF analyses. AB - Cerussite, an orthorhombic lead carbonate mineral, has a structure and physical properties that cannot be understood merely in terms of ionic anion-cation interactions. The nature of the chemical bonding in cerussite is analyzed by means of the quantum theory of atoms in molecules (QTAIM) and the analysis of the electron localization function (ELF). A long C-C attractive interaction (3.077 A) along the c axis of the cerussite structure is evidenced by the presence of bond critical points between the C atoms of the CO(3)(2-) molecular groups. It is proposed that the Pb-O interactions, which are mostly ionic in nature, disturb the structure of the CO(3)(2-) molecular groups and promote their interaction along the c axis. The importance of this long-range interaction in the high pressure crystal chemistry of carbonate minerals and in the explanation of some crystal growth features observed for orthorhombic carbonates is also discussed in this work. PMID- 25129663 TI - Transcaval retrograde transcatheter aortic valve replacement for patients with no other access: first-in-man experience with CoreValve. PMID- 25129665 TI - Fluoroscopic anatomy of left-sided heart structures for transcatheter interventions: insight from multislice computed tomography. AB - With the introduction of transcatheter structural heart therapies, cardiologists are increasingly aware of the importance of understanding anatomical details of left-sided heart structures. Understanding fluoroscopic cardiac anatomy can facilitate optimal positioning and deployment of prostheses during transcatheter valve repair/replacement, left atrial appendage occlusion, septal defect closure, and paravalvular leak closure. It is possible to use multislice computed tomography to determine optimal fluoroscopic viewing angles for such transcatheter therapies. The purpose of this paper is to describe how optimal fluoroscopic viewing angles of left-sided heart structures can be obtained using computed tomography. Two- and 3-chamber views are described and may become standard in the context of transcatheter structural heart interventions. PMID- 25129666 TI - Real-time assessment of myocardial viability in the catheterization laboratory using the intracoronary electrograms recorded by the PTCA guidewire in patients with left ventricular dysfunction: comparison with delayed-enhancement magnetic resonance imaging. AB - OBJECTIVES: This study aimed to determine whether the intracoronary electrograms (IC-EGMs) recorded using a standard percutaneous coronary intervention guidewire could provide myocardial viability information. BACKGROUND: The revascularization of dysfunctional but viable myocardium may confer prognostic benefits compared with medical therapy in patients with post-ischemic heart failure. However, knowledge of myocardial viability is often unavailable at the time of the procedure. METHODS: The peak-to-peak voltage of 317 IC-EGMs recordings from 25 patients with a previous myocardial infarction and systolic dysfunction were matched with corresponding delayed-enhancement magnetic resonance imaging sites using a 17-segment model of the left ventricle. RESULTS: Sixty-seven recordings were obtained from segments classified as complete scar on delayed-enhancement magnetic resonance imaging (group A), 162 from partially viable segments (group B), and 88 from fully viable segments (group C). Three high-pass (HP) filters (0.5, 30, and 100 Hz) were applied to the signals to modulate their spatial resolution. For all filters, the peak-to-peak voltage significantly decreased from group C to group B to group A (p < 0.001 for all comparisons). When receiver operating characteristic analysis was used to compare nonviable (group A) with viable (group B + C) segments, the optimal discriminating voltages were 4.6, 2.2, and 0.78 mV for, respectively, HP-0.5, HP-30, and HP-100 filters, with a sensitivity of 92%, 94%, and 99% and a specificity of 70%, 79%, and 69%. CONCLUSIONS: The amplitude of the IC-EGMs discriminates viable from nonviable left ventricular segments. Because this technique is simple and inexpensive and provides real-time results, it is potentially useful to aid decision making in the catheterization laboratory. PMID- 25129664 TI - Mechanisms of atherothrombosis and vascular response to primary percutaneous coronary intervention in women versus men with acute myocardial infarction: results of the OCTAVIA study. AB - OBJECTIVES: This study sought to assess in vivo sex differences in the pathophysiology of ST-segment elevation myocardial infarction (STEMI) and vascular response to primary percutaneous coronary intervention (PCI). BACKGROUND: There is no consensus on whether differences in the pathophysiology of STEMI and response to primary PCI between women and men reflect biological factors as opposed to differences in age. METHODS: In this prospective, multicenter study, 140 age-matched men and women with STEMI undergoing primary PCI with everolimus-eluting stent were investigated with intravascular optical coherence tomography, histopathology-immunohistochemistry of thrombus aspirates, and serum biomarkers. Primary endpoints were the percentages of culprit plaque rupture at baseline and everolimus-eluting stent strut coverage at 9-month follow up as determined by optical coherence tomography. RESULTS: Men and women had similar rates of plaque rupture (50.0% vs. 48.4%; risk ratio [RR]: 1.03; 95% confidence interval [CI]: 0.73 to 1.47; p = 0.56). Nonruptured/eroded plaques comprised 25% of all cases (p = 0.86 in men vs. women). There were no sex differences in composition of aspirated thrombus and immune and inflammatory serum biomarkers. At 9 months, women had similar strut coverage (90.9% vs. 92.5%; difference in medians: RR: 0.2%; 95% CI: -0.4% to 1.3%; p = 0.89) and amount of in-stent neointimal obstruction (10.3% vs. 10.6%; p = 0.76) as men did. There were no sex differences in clinical outcome either at 30-day or 1-year follow-up. CONCLUSIONS: In patients presenting with STEMI undergoing primary PCI, no differences in culprit plaque morphology and factors associated with coronary thrombosis were observed between age-matched men and women. Women also showed similar vascular healing response to everolimus-eluting stents as men did. (Optical Coherence Tomography Assessment of Gender Diversity In Primary Angioplasty: The OCTAVIA Trial [OCTAVIA]; NCT01377207). PMID- 25129667 TI - Thrombus formation at the MitraClip system during percutaneous mitral valve repair. PMID- 25129668 TI - Transapical transcatheter aortic valve for severe aortic regurgitation: expanding the limits. AB - OBJECTIVES: This study sought to evaluate the self-expandable ACURATE TA device (Symetis SA, Ecublens, Switzerland) in a cohort of patients with pure aortic regurgitation (AR). BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been initially considered as an alternative for high-risk patients with aortic stenosis. Although the current experience is limited, TAVR might be also an alternative to treat patients with pure, severe AR. METHODS: Between April 2012 and December 2013, a total of 8 high-risk patients with pure, severe AR were enrolled (grade III+). Clinical and hemodynamic data as well as data on device and procedure parameters and outcomes were collected. RESULTS: Patient mean was 72.5 +/- 8.4 years, and 37.5% of patients were female. Logistic EuroSCORE was 34.0 +/- 7.9% and the Society of Thoracic Surgeons score was 7.3 +/- 3.3% on average. Two patients had undergone emergency aortic operation before due to acute type A aortic dissection, and both were treated by replacement of the ascending aorta (including root reconstruction) and the aortic arch combined with or without E-vita Open stent graft (Jotec GmbH, Hechingen, Germany) (January 2011 and March 2012), whereas the other patients experienced primary AR. All patients underwent successful transapical TAVR with the transapical ACURATE TA device (size small, n = 1, size medium, n = 3, size large, n = 4) without any intraprocedural complications according to the Valve Academic Research Consortium 2 criteria. Post-procedure AR grade I+ or lower, as revealed by transoesophageal echocardiography and angiography, was present in all 8 patients. At 30 days, the stroke incidence and all-cause mortality rate were 0%. CONCLUSIONS: This small single-center series demonstrates the feasibility of transapical TAVR with the self-expandable ACURATE TA device in high-risk patients with severe AR. PMID- 25129669 TI - Left anterior descending coronary artery occlusion during transcatheter pulmonary valve implantation: successful rescue percutaneous revascularization. PMID- 25129670 TI - Contralateral embolization of intima after transfemoral aortic valve replacement. PMID- 25129671 TI - Instant stent-accentuated 3-dimensional optical coherence tomography of a bifurcation lesion treated with reverse minimum overlapping culotte stenting. PMID- 25129672 TI - Initial German experience with transapical implantation of a second-generation transcatheter heart valve for the treatment of aortic regurgitation. AB - OBJECTIVES: This analysis reports on the initial German multicenter experience with the JenaValve (JenaValve Technology GmbH, Munich, Germany) transcatheter heart valve for the treatment of pure aortic regurgitation. BACKGROUND: Experience with transcatheter aortic valve implantation (TAVI) for severe aortic regurgitation is limited due to the risk of insufficient anchoring of the valve stent within the noncalcified aortic annulus. METHODS: Transapical TAVI with a JenaValve for the treatment of severe aortic regurgitation was performed in 31 patients (age 73.8 +/- 9.1 years) in 9 German centers. All patients were considered high risk for surgery (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation] 23.6 +/- 14.5%) according to a local heart team consensus. Procedural results and clinical outcomes up to 6 months were analyzed. RESULTS: Implantation was successful in 30 of 31 cases (aortic annulus diameter 24.7 +/- 1.5 mm); transcatheter heart valve dislodgement necessitated valve-in valve implantation in 1 patient. Post-procedural aortic regurgitation was none/trace in 28 of 31 and mild in 3 of 31 patients. During follow-up, 2 patients underwent valvular reinterventions (surgical aortic valve replacement for endocarditis, valve-in-valve implantation for increasing paravalvular regurgitation). All-cause mortality was 12.9% and 19.3% at 30 days and 6 months, respectively. In the remaining patients, a significant improvement in New York Heart Association class was observed and persisted up to 6 months after TAVI. CONCLUSIONS: Aortic regurgitation remains a challenging pathology for TAVI. After initial demonstration of feasibility, this multicenter study revealed the JenaValve transcatheter heart valve as a reasonable option in this subset of patients. However, a significant early noncardiac mortality related to the high risk population emphasizes the need for careful patient selection. PMID- 25129673 TI - Impact of combined prenatal ethanol and prenatal stress exposures on markers of activity-dependent synaptic plasticity in rat dentate gyrus. AB - Prenatal ethanol exposure and prenatal stress can each cause long-lasting deficits in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms underlying these perturbations following a learning event are still poorly understood. We examined the effects of prenatal ethanol exposure and prenatal stress exposure, either alone or in combination, on the cytosolic expression of activity-regulated cytoskeletal (ARC) protein and the synaptosomal expression of AMPA-glutamate receptor subunits (GluA1 and GluA2) in dentate gyrus of female adult offspring under baseline conditions and after 2 trial trace conditioning (TTTC). Surprisingly, baseline cytoplasmic ARC expression was significantly elevated in both prenatal treatment groups. In contrast, synaptosomal GluA1 receptor subunit expression was decreased in both prenatal treatment groups. GluA2 subunit expression was elevated in the prenatal stress group. TTTC did not alter ARC levels compared to an unpaired behavioral control (UPC) group in any of the 4 prenatal treatment groups. In contrast, TTTC significantly elevated both synaptosomal GluA1 and GluA2 subunit expression relative to the UPC group in control offspring, an effect that was not observed in any of the other 3 prenatal treatment groups. Given ARC's role in regulating synaptosomal AMPA receptors, these results suggest that prenatal ethanol-induced or prenatal stress exposure-induced increases in baseline ARC levels could contribute to reductions in both baseline and activity-dependent changes in AMPA receptors in a manner that diminishes the role of AMPA receptors in dentate gyrus synaptic plasticity and hippocampal-sensitive learning. PMID- 25129675 TI - Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects. AB - BACKGROUND: Currently, measurement of serum tryptase level is the most commonly used test to estimate the need for bone marrow biopsy in patients suspected to have indolent systemic mastocytosis (ISM). Yet tryptase levels do not solely reflect the mast cell load and can be elevated by overweight, older age, and impaired renal function. The influence of these factors on urinary methylhistamine (MH) and methylimidazole acetic acid (MIMA) is still unknown. OBJECTIVE: We investigated the impact of age, body mass index (BMI), and kidney function on the diagnostic accuracy of tryptase, MH, and MIMA to select the most optimal test indicating the necessity of a bone marrow biopsy in ISM-suspected patients. METHODS: Retrospective data analysis of all adults in whom bone marrow investigations were performed because of high clinical suspicion and/or elevated tryptase, MH, or MIMA. RESULTS: 194 subjects were included. ISM was present in 112 and absent in 82 subjects (non-ISM). Tryptase was elevated by age and body weight in non-ISM subjects and by BMI in ISM subjects; however, these factors did not influence MH or MIMA. In the total study population, the diagnostic accuracy of tryptase, MH, and MIMA were comparable (area under the curve 0.80, 0.80, and 0.83). In subjects >50 years with a BMI >25 kg/m(2), the diagnostic accuracy of MIMA was higher compared with that of tryptase (area under the curve 0.93 vs 0.74; P = .011). CONCLUSION: In ISM-suspected patients >50 years with a BMI of >25 kg/m(2), MIMA has a greater value compared with tryptase in estimating the need for bone marrow biopsy. PMID- 25129676 TI - B-cell linear epitopes mapping of antigen-5 allergen from Polybia paulista wasp venom. PMID- 25129674 TI - Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics causes many subtle changes in gene expression. AB - To elucidate the effects of a controlled exposure to ethanol on gene expression, we studied lymphoblastoid cell lines (LCLs) from 21 alcoholics and 21 controls. We cultured each cell line for 24 h with and without 75 mM ethanol and measured gene expression using microarrays. Differences in expression between LCLs from alcoholics and controls included 13 genes previously identified as associated with alcoholism or related traits, including KCNA3, DICER1, ZNF415, CAT, SLC9A9, and PPARGC1B. The paired design allowed us to detect very small changes due to ethanol treatment: ethanol altered the expression of 37% of the probe sets (51% of the unique named genes) expressed in these LCLs, most by modest amounts. Ninety-nine percent of the named genes expressed in the LCLs were also expressed in brain. Key pathways affected by ethanol include cytokine, TNF, and NFkappaB signaling. Among the genes affected by ethanol were ANK3, EPHB1, SLC1A1, SLC9A9, NRD1, and SH3BP5, which were reported to be associated with alcoholism or related phenotypes in 2 genome-wide association studies. Genes that either differed in expression between alcoholics and controls or were affected by ethanol exposure are candidates for further study. PMID- 25129677 TI - Influence of early-life exposures on food sensitization and food allergy in an inner-city birth cohort. AB - OBJECTIVE: Previous data suggest that food allergy (FA) might be more common in inner-city children; however, these studies have not collected data on both sensitization and clinical reactivity or early-life exposures. METHODS: Children in the Urban Environment and Childhood Asthma birth cohort were followed through age 5 years. Household exposures, diet, clinical history, and physical examinations were assessed yearly; levels of specific IgE to milk, egg, and peanut were measured at 1, 2, 3, and 5 years of age. On the basis of sensitization (IgE >=0.35 kU/L) and clinical history over the 5-year period, children were classified as having FA or being possibly allergic, sensitized but tolerant, or not allergic/not sensitized. RESULTS: Five hundred sixteen children were included. Overall, 55.4% were sensitized (milk, 46.7%; egg, 31.0%; and peanut, 20.9%), whereas 9.9% were categorized as having FA (peanut, 6.0%; egg, 4.3%; and milk, 2.7%; 2.5% to >1 food). The remaining children were categorized as possibly allergic (17.0%), sensitized but tolerant (28.5%), and not sensitized (44.6%). Eighteen (3.5%) reported reactions to foods for which IgE levels were not measured. Food-specific IgE levels were similar in children with FA versus sensitized but tolerant children, except for egg, levels of which were higher in patients with FA at ages 1 and 2 years. FA was associated with recurrent wheeze, eczema, aeroallergen sensitization, male sex, breast-feeding, and lower endotoxin exposure in year 1 but not with race/ethnicity, income, tobacco exposure, maternal stress, or early introduction of solid foods. CONCLUSIONS: Even given that this was designed to be a high-risk cohort, the cumulative incidence of FA is extremely high, especially considering the strict definition of FA that was applied and that only 3 common allergens were included. PMID- 25129678 TI - Biological clustering supports both "Dutch" and "British" hypotheses of asthma and chronic obstructive pulmonary disease. AB - BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. OBJECTIVE: We sought to determine, in terms of their sputum cellular and mediator profiles, the extent to which they represent distinct or overlapping conditions supporting either the "British" or "Dutch" hypotheses of airway disease pathogenesis. METHODS: We compared the clinical and physiological characteristics and sputum mediators between 86 subjects with severe asthma and 75 with moderate-to-severe COPD. Biological subgroups were determined using factor and cluster analyses on 18 sputum cytokines. The subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58) cohorts. Two techniques were used to assign the validation subjects to subgroups: linear discriminant analysis, or the best identified discriminator (single cytokine) in combination with subject disease status (asthma or COPD). RESULTS: Discriminant analysis distinguished severe asthma from COPD completely using a combination of clinical and biological variables. Factor and cluster analyses of the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and neutrophilic. Validation subjects were classified into 3 subgroups using discriminant analysis, or disease status with a binary assessment of sputum IL 1beta expression. Sputum cellular and cytokine profiles of the validation subgroups were similar to the subgroups from the test study. CONCLUSIONS: Sputum cytokine profiling can determine distinct and overlapping groups of subjects with asthma and COPD, supporting both the British and Dutch hypotheses. These findings may contribute to improved patient classification to enable stratified medicine. PMID- 25129679 TI - Total transcriptome, proteome, and allergome of Johnson grass pollen, which is important for allergic rhinitis in subtropical regions. AB - BACKGROUND: Genomic data are lacking for many allergen sources. To circumvent this limitation, we implemented a strategy to reveal the repertoire of pollen allergens of a grass with clinical importance in subtropical regions, where an increasing proportion of the world's population resides. OBJECTIVE: We sought to identify and immunologically characterize the allergenic components of the Panicoideae Johnson grass pollen (JGP; Sorghum halepense). METHODS: The total pollen transcriptome, proteome, and allergome of JGP were documented. Serum IgE reactivities with pollen and purified allergens were assessed in 64 patients with grass pollen allergy from a subtropical region. RESULTS: Purified Sor h 1 and Sor h 13 were identified as clinically important allergen components of JGP with serum IgE reactivity in 49 (76%) and 28 (43.8%), respectively, of patients with grass pollen allergy. Within whole JGP, multiple cDNA transcripts and peptide spectra belonging to grass pollen allergen families 1, 2, 4, 7, 11, 12, 13, and 25 were identified. Pollen allergens restricted to subtropical grasses (groups 22 24) were also present within the JGP transcriptome and proteome. Mass spectrometry confirmed the IgE-reactive components of JGP included isoforms of Sor h 1, Sor h 2, Sor h 13, and Sor h 23. CONCLUSION: Our integrated molecular approach revealed qualitative differences between the allergenic components of JGP and temperate grass pollens. Knowledge of these newly identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with grass pollen allergy in subtropical regions and reduce the burden of allergic respiratory disease globally. PMID- 25129682 TI - Sputum adiponectin as a marker for western red cedar asthma. PMID- 25129681 TI - Short- and long-term efficacy of prednisolone for first acute rhinovirus-induced wheezing episode. AB - BACKGROUND: Rhinovirus-induced wheezing is an important risk factor for recurrent wheezing. There are no randomized controlled trials on the effect of systemic corticosteroids in patients with this disease. OBJECTIVE: We sought to study the short- and long-term effects of prednisolone treatment of the first acute, moderate-to-severe, rhinovirus-induced wheezing episode in young children. METHODS: After confirming rhinovirus from nasopharyngeal aspirate by using PCR, 79 children with a first wheezing episode at age 3 to 23 months were randomized to receive oral prednisolone (first dose of 2 mg/kg, followed by 2 mg/kg/d in 2 divided doses for 3 days) or placebo. The trial was double blind throughout the 12-month follow-up. The primary outcomes were long term: new physician-confirmed wheezing episode within 2 months, number of physician-confirmed wheezing episodes within 12 months, and initiation of regular controller medication for asthma symptoms within 12 months. The primary interaction analysis examined rhinovirus load. RESULTS: Seventy-four patients completed the study (mean age, 13 months; 28% atopic). Long-term outcomes did not differ between groups (all P >= .30). For short-term outcomes, the prednisolone group had less cough, rhinitis, noisy breathing, severe breathing difficulties, and nocturnal respiratory symptoms at home within 2 weeks (all P < .05). The 25 children with greater than 7000 rhinovirus copies/mL (most sensitive cutoff) benefitted from prednisolone in terms of less risk of physician-confirmed recurrence within 2 and 12 months compared with placebo (both P < .05). CONCLUSIONS: Prednisolone cannot be routinely recommended for all young children experiencing their first acute, moderate-to-severe, rhinovirus-induced wheezing episode. Prednisolone might be beneficial in a subgroup of children with high viral loads. PMID- 25129680 TI - Eosinophil-dependent skin innervation and itching following contact toxicant exposure in mice. AB - BACKGROUND: Contact toxicant reactions are accompanied by localized skin inflammation and concomitant increases in site-specific itch responses. The role(s) of eosinophils in these reactions is poorly understood. However, previous studies have suggested that localized eosinophil-nerve interactions at sites of inflammation significantly alter tissue innervation. OBJECTIVE: To define a potential mechanistic link between eosinophils and neurosensory responses in the skin leading to itching. METHODS: BALB/cJ mice were exposed to different contact toxicants, identifying trimellitic anhydride (TMA) for further study on the basis of inducing a robust eosinophilia accompanied by degranulation. Subsequent studies using TMA were performed with wild type versus eosinophil-deficient PHIL mice, assessing edematous responses and remodeling events such as sensory nerve innervation of the skin and induced pathophysiological responses (ie, itching). RESULTS: Exposure to TMA, but not dinitrofluorobenzene, resulted in a robust eosinophil skin infiltrate accompanied by significant levels of degranulation. Follow-up studies using TMA with wild type versus eosinophil-deficient PHIL mice showed that the induced edematous responses and histopathology were, in part, causatively linked with the presence of eosinophils. Significantly, these data also demonstrated that eosinophil-mediated events correlated with a significant increase in substance P content of the cutaneous nerves and an accompanying increase in itching, both of which were abolished in the absence of eosinophils. CONCLUSIONS: Eosinophil-mediated events following TMA contact toxicant reactions increase skin sensory nerve substance P and, in turn, increase itching responses. Thus, eosinophil-nerve interactions provide a potential mechanistic link between eosinophil-mediated events and neurosensory responses following exposure to some contact toxicants. PMID- 25129684 TI - The structure and validity of directional measures of appearance social comparison among emerging adults in China. AB - We evaluated the structure and validity of the Upward Appearance Comparison Scale (UPACS) and Downward Appearance Comparison Scale (DACS) (O'Brien et al., 2009) in Chinese samples. In Study 1, principal component analysis on an initial sample (427 women, 123 men) and confirmatory factor analysis on another sample (447 women, 121 men) found that a 15-item, two component model had the best overall fit. Derived components had moderate correlations with most conceptually related measures and low correlations with less conceptually related indices. Study 2 participants (310 women, 201 men) completed the UPACS and DACS as well as measures of disordered eating, fatness concern, and negative affect; they were re assessed one year later. Baseline UPACS scores predicted changes in disordered eating for women and fatness concerns for men, independent of initial disturbances, but DACS responses were not related to outcomes. Findings highlighted the potential utility of derived UPACS and DACS within a Chinese context. PMID- 25129685 TI - "Appearance potent"? A content analysis of UK gay and straight men's magazines. AB - With little actual appraisal, a more 'appearance potent' (i.e., a reverence for appearance ideals) subculture has been used to explain gay men's greater body dissatisfaction in comparison to straight men's. This study sought to assess the respective appearance potency of each subculture by a content analysis of 32 issues of the most read gay (Attitude, Gay Times) and straight men's magazines (Men's Health, FHM) in the UK. Images of men and women were coded for their physical characteristics, objectification and nudity, as were the number of appearance adverts and articles. The gay men's magazines featured more images of men that were appearance ideal, nude and sexualized than the straight men's magazines. The converse was true for the images of women and appearance adverts. Although more research is needed to understand the effect of this content on the viewer, the findings are consistent with a more appearance potent gay male subculture. PMID- 25129683 TI - Stress and asthma: novel insights on genetic, epigenetic, and immunologic mechanisms. AB - In the United States the economically disadvantaged and some ethnic minorities are often exposed to chronic psychosocial stressors and disproportionately affected by asthma. Current evidence suggests a causal association between chronic psychosocial stress and asthma or asthma morbidity. Recent findings suggest potential mechanisms underlying this association, including changes in the methylation and expression of genes that regulate behavioral, autonomic, neuroendocrine, and immunologic responses to stress. There is also evidence suggesting the existence of susceptibility genes that predispose chronically stressed youth to both post-traumatic stress disorder and asthma. In this review we critically examine published evidence and suggest future directions for research in this field. PMID- 25129687 TI - Editorial overview: Mechanisms: Chemical and computational probes of biological mechanism. PMID- 25129686 TI - The role of media and peer influences in Australian women's attitudes towards cosmetic surgery. AB - The study aimed to examine the influence of media and peers on attitudes towards cosmetic surgery using a sociocultural framework. A sample of 351 Australian women aged 18-69 years completed measures of media exposure, friend conversations, internalisation of appearance ideals, appearance comparison, body dissatisfaction, and attitudes towards cosmetic surgery. Correlational analysis showed that almost all media and friend variables were significantly correlated with positive attitudes towards cosmetic surgery. A structural equation model based on the sociocultural model showed a good level of fit to the data. The effects of media exposure and friend conversations on body dissatisfaction and attitudes towards cosmetic surgery were mediated by internalisation. We concluded that media exposure and friend conversations affected attitudes towards cosmetic surgery both directly and indirectly. Our results contribute to the understanding of the sociocultural mechanisms underlying women's motivations for cosmetic surgery. PMID- 25129688 TI - A pitfall in diagnosing Cushing's disease: ectopic ACTH-producing pituitary adenoma in the sphenoid sinus. AB - PURPOSE: To show a rare case of Cushing's disease and possible cause of failed transsphenoidal surgery. METHOD: We report on a 50-year-old woman suffering from ACTH-dependent Cushing's syndrome. Endocrinological work-up including low dose/high-dose dexamethasone test (Liddle-test) and CRH test were clearly compatible with pituitary origin. Although an MRI showed no pituitary tumor, CRH stimulated petrosal sinus sampling revealed a significant central-peripheral gradient in ACTH concentrations, rendering Cushing's disease very likely. The patient underwent transsphenoidal surgery with negative exploration of the pituitary gland. After intraoperative re-evaluation of the preoperative MRI, a "polyp" at the bottom of the sphenoid sinus was identified. The intraoperative microscopic aspect as well as instantaneous sections and cytology of a biopsy confirmed an adenoma, which was then removed. Histological analysis demonstrated an ACTH-producing pituitary adenoma adjacent to respiratory mucous membrane consisting of ciliated epithelium with submucous connective tissue. Postoperatively, ACTH concentrations were decreased and intermittent hydrocortisone substitution treatment was initiated. At the 3-month follow up, Cushing's stigmata were found to be alleviated and the hydrocortisone dosage could be reduced. CONCLUSION: Ectopic pituitary adenoma tissue causing Cushing's disease is extremely rare but a potential cause for surgical failure or re evaluation. PMID- 25129689 TI - Effects of introducing Xpert MTB/RIF test on multi-drug resistant tuberculosis diagnosis in KwaZulu-Natal South Africa. AB - BACKGROUND: An algorithm instituted following Xpert MTB/RIF (Xpert) introduction in South Africa advocates for treating all Xpert rifampicin resistant patients as MDR-TB cases while awaiting confirmation by phenotypic or genotypic drug susceptibility testing. This study evaluates how the Xpert has influenced the diagnosis and management of drug resistant TB in the highest burdened district of KwaZulu-Natal Province. METHODS: Data was retrospectively collected from all patients with rifampicin resistance on Xpert performed between March 2011 and April 2012. Xpert results were compared with those of phenotypic and/genotypic drug susceptibility testing. Patients' records were used to determine the time to treatment initiation. RESULTS: Out of 637 patients tested by Xpert, 50% had confirmatory results, of which a third were sent on the same day as Xpert test. The rate of rifampicin discordance and monoresistance was 8.8% and 13.4% respectively and there was no difference between phenotypic and genotypic confirmation. Among those who had been initiated on treatment, 28%, 40%, 21% and 8% of patients commenced within 2 weeks, 1 month, 2 months and 3 months of Xpert testing respectively, while the remaining 3% were observed without treatment. CONCLUSION: This study emphasizes the importance of complying with the algorithm in confirming all Xpert rif resistant cases so as to ensure proper management of these patients. Despite the rapidity of the Xpert results, only about 70% of patients had been initiated treatment at one month. Therefore there is a definite need to improve the health systems in order to improve on these delays. PMID- 25129691 TI - Women's age and embryo developmental speed accurately predict clinical pregnancy after single vitrified-warmed blastocyst transfer. AB - The aim of this study was to establish a simple, objective blastocyst grading system using women's age and embryo developmental speed to predict clinical pregnancy after single vitrified-warmed blastocyst transfer. A 6-year retrospective cohort study was conducted in a private infertility centre. A total of 7341 single vitrified-armed blastocyst transfer cycles were included, divided into those carried out between 2006 and 2011 (6046 cycles) and 2012 (1295 cycles). Clinical pregnancy rate, ongoing pregnancy rate and delivery rates were stratified by women's age (<35, 35-37, 38-39, 40-41, 42-45 years) and time to blastocyst expansion (<120, 120-129, 130-139, 140-149, >149 h) as embryo developmental speed. In all the age groups, clinical pregnancy rate, ongoing pregnancy rate and delivery rates decreased as the embryo developmental speed decreased (P < 0.0001). A simple five-grade score based on women's age and embryo developmental speed was determined by actual clinical pregnancy rates observed in the 2006-2011 cohort. Subsequently, the novel grading score was validated in the 2012 cohort (1295 cycles), finding an excellent association. In conclusion, we established a novel blastocyst grading system using women's age and embryo developmental speed as objective parameters. PMID- 25129692 TI - Cryobanking of human ovarian tissue: Do women still want their tissue stored beyond 5 years? AB - Cryopreservation of ovarian tissue is one way of preserving fertility in young women with a malignant disease or other disorders that require gonadotoxic treatment. The purpose of the study was to explore how many women remained interested in continued cryostorage of their ovarian tissue beyond an initial 5 year period. Between 1999 and 2006, a total of 201 girls and young women had one ovary cryopreserved for fertility preservation in Denmark. One hundred of these met our inclusion criteria, which included a follow-up period of at least 5 years, and were mailed a questionnaire. The response rate was 95%. Sixteen of the patients (17%) stated that they wanted disposal of their tissue; the main reason was completion of family (63%). The mean age of those requesting disposal was 36.6 years, whereas those still wanting their tissue stored were significantly younger, with a mean age of 33.0 years (P < 0.008). In conclusion, most women with ovarian tissue cryobanked requested continued cryostorage after an initial period of at least 5 years. The main reason for requesting disposal was successful completion of a family. PMID- 25129690 TI - Targeted sequencing by proximity ligation for comprehensive variant detection and local haplotyping. AB - Despite developments in targeted gene sequencing and whole-genome analysis techniques, the robust detection of all genetic variation, including structural variants, in and around genes of interest and in an allele-specific manner remains a challenge. Here we present targeted locus amplification (TLA), a strategy to selectively amplify and sequence entire genes on the basis of the crosslinking of physically proximal sequences. We show that, unlike other targeted re-sequencing methods, TLA works without detailed prior locus information, as one or a few primer pairs are sufficient for sequencing tens to hundreds of kilobases of surrounding DNA. This enables robust detection of single nucleotide variants, structural variants and gene fusions in clinically relevant genes, including BRCA1 and BRCA2, and enables haplotyping. We show that TLA can also be used to uncover insertion sites and sequences of integrated transgenes and viruses. TLA therefore promises to be a useful method in genetic research and diagnostics when comprehensive or allele-specific genetic information is needed. PMID- 25129693 TI - The social context for surrogates' motivations and satisfaction. AB - This Commentary takes up two of the main findings by Imrie and Jadva's study, namely surrogates' satisfaction with the post-surrogacy contact with intended parents and their motivation for surrogacy. It argues that the findings are in keeping with other qualitative research on surrogacy and that this similarity is not the result of the similarity of surrogates' psychological makeup. The Commentary highlights the centrality of social meanings and definitions, and following Howard Becker, insists on taking into account the collective doings that inform and shape individual feelings and behaviour. PMID- 25129695 TI - Bayesian Proteoform Modeling Improves Protein Quantification of Global Proteomic Measurements. AB - As the capability of mass spectrometry-based proteomics has matured, tens of thousands of peptides can be measured simultaneously, which has the benefit of offering a systems view of protein expression. However, a major challenge is that with an increase in throughput, protein quantification estimation from the native measured peptides has become a computational task. A limitation to existing computationally-driven protein quantification methods is that most ignore protein variation, such as alternate splicing of the RNA transcript and post translational modifications or other possible proteoforms, which will affect a significant fraction of the proteome. The consequence of this assumption is that statistical inference at the protein level, and consequently downstream analyses, such as network and pathway modeling, have only limited power for biomarker discovery. Here, we describe a Bayesian model (BP-Quant) that uses statistically derived peptides signatures to identify peptides that are outside the dominant pattern, or the existence of multiple over-expressed patterns to improve relative protein abundance estimates. It is a research-driven approach that utilizes the objectives of the experiment, defined in the context of a standard statistical hypothesis, to identify a set of peptides exhibiting similar statistical behavior relating to a protein. This approach infers that changes in relative protein abundance can be used as a surrogate for changes in function, without necessarily taking into account the effect of differential post-translational modifications, processing, or splicing in altering protein function. We verify the approach using a dilution study from mouse plasma samples and demonstrate that BP-Quant achieves similar accuracy as the current state-of-the-art methods at proteoform identification with significantly better specificity. BP-Quant is available as a MatLab (r) and R packages at https://github.com/PNNL-Comp-Mass-Spec/BP-Quant. PMID- 25129696 TI - Multifunctional graphene quantum dots for simultaneous targeted cellular imaging and drug delivery. AB - This study demonstrates that ligand-modified graphene quantum dots (GQDs) facilitate the simultaneous operation of multiple tasks without the need for external dyes. These tasks include selective cell labeling, targeted drug delivery, and real-time monitoring of cellular uptake. Folic acid (FA)-conjugated GQDs are synthesized and utilized to load the antitumor drug doxorubicin (DOX). The fabricated nanoassembly can unambiguously discriminate cancer cells from normal cells and efficiently deliver the drug to targeted cells. The inherent stable fluorescence of GQDs enables real-time monitoring of the cellular uptake of the DOX-GQD-FA nanoassembly and the consequent release of drugs. The nanoassembly is specifically internalized rapidly by HeLa cells via receptor mediated endocytosis, whereas DOX release and accumulation are prolonged. In vitro toxicity data suggest that the DOX-GQD-FA nanoassembly can target HeLa cells differentially and efficiently while exhibiting significantly reduced cytotoxicity to non-target cells. PMID- 25129697 TI - Adsorption at the biocompatible alpha-pinene-water interface and emulsifying properties of two eco-friendly surfactants. AB - In this contribution, we provide an accurate characterization at the alpha pinene/water interface of two commercial polyoxytheylene glycerol ester surfactants which differ in the number of ethylene oxide (EO) groups, comprising a systematic analysis of interfacial pressure isotherms, dynamic curves, interfacial rheology and emulsifying properties. Polyoxyethylene glycerol esters derived from cocoa oil are non-ionic surfactants obtained from a renewable source which fulfill the environmental and toxicological requirements to be used as eco friendly emulsifying agents. alpha-Pinene is a renewable biosolvent completely insoluble in water, which could find numerous applications. Interfacial rheology and equilibrium interfacial pressure data fitted a rigorous reorientation model that assumes that the surfactant molecules, when adsorbed at the interface, can acquire two orientations. The surfactant with the highest number of EO groups (Levenol C201) turned out to be more surface active at the alpha-pinene/water interface. In addition, the surfactant with the lowest number of EO groups (Levenol H&B) is solubilized into the adjacent oil phase. Slightly concentrated alpha-pinene emulsions were obtained using both surfactants. Nevertheless, more stable alpha-pinene emulsions with smaller droplet sizes and lower polidispersity were obtained when Levenol C201 was used as emulsifier instead of Levenol H&B. The systematic characterization presented in this work provides important new findings on the interfacial and emulsifying properties of polyoxytheylene glycerol ester surfactants, which can be applied in the rational development of new biocompatible products. PMID- 25129698 TI - Exercise-based injury prevention in child and adolescent sport: a systematic review and meta-analysis. AB - BACKGROUND: The promotion of sport and physical activity (PA) for children is widely recommended to support a healthy lifestyle, but being engaged in sport bears the risk of sustaining injuries. Injuries, in turn, can lead to a reduction in current and future involvement in PA and, therefore, may negatively affect future health as well as quality of life. Thus, sports injury prevention is of particular importance in youth. OBJECTIVE: The aim of this systematic review was to quantify the effectiveness of exercise-based injury prevention programs in child and adolescent sport in general, and with respect to different characteristics of the target group, injury prevention program, and outcome variables. DATA SOURCES: An Internet-based literature search was conducted in six databases (CINAHL, Cochrane, EMBASE, ISI Web of Science, PubMed, SPORTDiscus) using the following search terms with Boolean conjunction: (sport injur* OR athletic injur* OR sport accident*) AND (prevent* OR prophylaxis OR avoidance) AND (child* OR adolescent OR youth). STUDY SELECTION: Randomized controlled trials and controlled intervention studies in organized sport, published in English in a peer-reviewed journal, analyzing the effects of an exercise-based injury prevention program in athletes younger than 19 years of age. DATA EXTRACTION: Two reviewers evaluated eligibility and methodological quality. Main outcome extracted was the rate ratio (RR). Statistical analyses were conducted using the inverse-variance random effects model. RESULTS: Twenty-one trials, conducted on a total of 27,561 athletes (median age 16.7 years [range 10.7 17.8]), were included. The overall RR was 0.54 (95% CI 0.45-0.67) [p < 0.001]. Girls profited more from injury prevention than boys (p = 0.05). Both prevention programs with a focus on specific injuries (RR 0.48 [95% CI 0.37-0.63]) and those aiming at all injuries (RR 0.62 [95% CI 0.48-0.81]) showed significant reduction effects. Pre-season and in-season interventions were similarly beneficial (p = 0.93). Studies on programs that include jumping/plyometric exercises showed a significant better (p = 0.002) injury preventive effect (RR 0.45 [95% CI 0.35 0.57], Z = 6.35, p < 0.001) than studies without such exercises (RR 0.74 [95% CI 0.61-0.90], Z = 3.03, p = 0.002). CONCLUSIONS: The results provide good evidence and clearly demonstrate beneficial effects of exercise-based injury prevention programs in youth sports as they can result in statistically significant and practically relevant injury reduction. In particular, multimodal programs including jumping/plyometric exercises can be recommended. However, there is a considerable lack of data for children (under 14 years of age) and for individual sports in general. Future research should include these groups and focus on the effect of specific exercises and compliance. PMID- 25129699 TI - The impact of exercise-induced bronchoconstriction on athletic performance: a systematic review. AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) describes the phenomenon of transient airway narrowing in association with physical activity. Although it may seem likely that EIB would have a detrimental impact on athletic performance, this has yet to be established. OBJECTIVES: The aim of this review is to provide a systematic appraisal of the current status of knowledge regarding EIB and exercise performance and to highlight potential mechanisms by which performance may be compromised by EIB. DATA SOURCES AND STUDY SELECTION: PubMed/Medline and EBSCO databases were searched up to May 2014 using the search parameter: [('exercise' OR 'athlete') AND ('asthma' OR 'bronchoconstriction' OR 'hypersensitivity') AND 'performance']. This search string returned 243 citations. After systematically reviewing all of the abstracts, 101 duplicate papers were removed, with 132 papers excluded for not including an exercise performance outcome measure. RESULTS: The remaining ten studies that met the initial criteria were included in this review; six evaluated the performance of physically active individuals with asthma and/or EIB while four assessed the effects of medication on performance in a comparable population. CONCLUSION: The evidence concludes that whilst it is reasonable to suspect that EIB does impact athletic performance, there is currently insufficient evidence to provide a definitive answer. PMID- 25129700 TI - Antibacterial phototoxic effects of synthetic asymmetric and glycosylated curcuminoids in aqueous formulations: studies on curcumin and curcuminoids. LIV. AB - The aim of this study was to evaluate the in vitro phototoxic potential of synthetic asymmetric and glycosylated curcuminoids on planktonic model bacteria by counting the colony forming units. The Gram-positive Enterococcus faecalis and the Gram-negative Escherichia coli were exposed to aqueous solutions of the curcuminoids (?2.5 MUM) in the presence or absence of selected pharmaceutical excipients (Pluronic F127, PEG 400 and HPgammaCD) in combination with a low irradiation dose (5 J/cm(2); lambdamax: 450 nm) of constant irradiance and time. All the asymmetric curcuminoids, but only one of the glycosylated curcuminoids demonstrated substantial phototoxic effect on E.faecalis (?4.7 log reduction). Only two of the asymmetric curcuminoids showed a moderate to low phototoxic effect on the more persistent E.coli. This study emphasized that aromatic hydroxyl substituents in the para-position are important to maintain the phototoxic potential of curcuminoids independent of molecular symmetry. Glycosylation of the aromatic substituents resulted in a substantial loss in phototoxicity towards planktonic bacteria, an apparent change in the non radiative S1-decay process and a weaker interaction with Pluronic F127 compared to the non-glycosylated curcuminoids. The selected excipients Pluronic F127, PEG 400 and HPgammaCD strongly influenced the phototoxic potential of the unsymmetrical, non-glycosylated compounds. PMID- 25129701 TI - A simple and effective method to synthesize fluorescent nanoparticles using tryptophan and light and their lethal effect against bacteria. AB - A simple, environmentally friendly and cost-effective method was used to synthesize silver nanoparticles using tryptophan and light. To prepare the nanoparticles, the following components were used: deionized water, silver nitrate, light and tryptophan. The effects of the tryptophan concentration and light exposure time on the formation of tryptophan silver nanoparticles (Tnnps) were studied. The synthesized Tnnps were characterized using transmission electron microscopy (TEM), absorption and fluorescence spectroscopy and zeta potential measurements. The synthesized Tnnps were nearly spherical, with sizes of approximately 17 nm. In addition, the antibacterial activity of Tnnps was determined by monitoring the growth curves of strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Serratia marcescens, and Enterococcus faecalis using the microdilution test. The Minimum Inhibitory Concentration (MIC) for 4 of 5 tested bacteria was determined to be between 20.0 and 17.5 MUg/mL for 48 h and between 22.5 and 20.0 MUg/mL for 72 h. PMID- 25129703 TI - A calculator for temporal artery biopsy result prediction in giant cell arteritis suspects. PMID- 25129702 TI - High tibial osteotomy. AB - High tibial osteotomy (HTO) is a widely accepted and performed procedure to treat medial knee arthrosis. The aim of this review is to evaluate the different surgical options in medial knee arthrosis, focusing on indications, patient's selection, long-term follow-up and survival analysis of HTO. Comparison and pooling of results are challenging because of different evaluation systems, small cohort number, and different surgical techniques. No differences have been described between opening and closing wedged HTO in terms of outcomes. Excellent early survivorship and good clinical outcomes were reported also with concomitant procedures. Correct indications, preoperative workup/planning, and technique selection are essential in achieving good results. The choice between opening and closing wedge osteotomy, graft selection in opening wedge HTO, comparison between HTO and unicompartmental knee arthroplasty, and the results of revised HTO to total knee replacement are currently under debate and will be discussed in the present review. PMID- 25129704 TI - Adjacent segment disease after anterior cervical interbody fusion: a multicenter retrospective study of 288 patients with long-term follow-up. AB - INTRODUCTION: Cervical discectomy with interbody fusion is a common procedure in spinal surgery. The resultant biomechanical alterations accelerate degeneration of the adjacent segment, but the contribution of natural degeneration to adjacent segment disease is unclear. OBJECTIVE: To assess the long-term rate of surgery to discs adjacent to cervical interbody fusion; and to assess the associated incidence of cervico-brachial neuralgia and radiological degeneration of adjacent discs. MATERIAL AND METHOD: A multicenter retrospective study included anterior cervical discectomy patients at a minimum of 10 years' follow-up. Clinical variables comprised pain, use of analgesics and surgical revision. Functional assessment was performed on the Neck Disability Index (NDI). Radiologic degeneration was assessed on the Goffin score based on cervical spine X-ray. RESULTS: Two hundred and eighty-eight patients were contacted and filled out the clinical questionnaire. Among the patients, 153 underwent radiological reassessment. Mean age was 46 years (range, 16-73 years). Mean follow-up was 14.5 years (12-18 years). The rate of surgical revision on a disc adjacent to the primary level was 5.9%. Frequent attacks of cervico-brachial neuralgia were reported in 20.5% of cases. Radiologic adjacent segment degeneration was found in 81.3% of cases over follow-up. There was a significant correlation between degree of radiologic adjacent segment degeneration and NDI (P=0.02). DISCUSSION: Degeneration adjacent to discectomy/fusion is partly due to aging. The present findings, however, agree with the literature and indicate accelerated degeneration in adjacent segments. These findings should be taken into account in treatment decision-making and suggest a possible interest of more physiological surgery such as arthroplasty. LEVEL OF EVIDENCE: IV - Multicenter retrospective study. PMID- 25129705 TI - The reliability of the anterior pelvic plane for computer navigated acetabular component placement during total hip arthroplasty: prospective study with the EOS imaging system. AB - INTRODUCTION: Computer navigated total hip arthroplasty is mostly based on the use of the anterior pelvic plane (APP) as a reference. EOS is a new imaging system that provides three-dimensional analysis of the pelvis in a functional position with a low dose of radiation. The aim of this study was to evaluate the reliability of the APP for placement of the cup during computer navigated THA using EOS. HYPOTHESIS: The reliability of the APP is limited for the placement of the acetabular cup during computer navigated THA. MATERIALS AND METHODS: This was a prospective monocentric study using the EOS imaging system evaluating 44 patients in the standing position three months after computer navigated THA (Orthopilot). Reproducibility of EOS measurements were analyzed using SterEOS software and the reliability of the navigation data for the position of the cup were assessed. RESULTS: Intra and interobserver reproducibility of the measurements of the orientation of the cup by EOS were good with correlation coefficients above 93% and 95% and confidence intervals of less than +/-5 degrees . Mean cup inclination and anteversion were 41.3 degrees and 20.9 degrees and 44.3 degrees and 29.5 degrees respectively in operatively and post-operatively. The differences between measurements of operative cup inclination using computer assisted navigation and the post-operative EOS measurements were significant (P<0.05) with a correlation coefficient of less than 40%. DISCUSSION: Our study confirms the lack of precision of the APP as a reference for positioning of the acetabular component, especially in relation to anteversion. Although for many years the APP was considered to be a global reference, in fact, it is subject to significant inter-individual variations and variations during changes in position. These factors, associated with the difficulty of determining the preoperative APP, explain the lack of reliability of this reference. Preoperative evaluation of the orientation of APP by EOS and its integration into the navigation system could help the operator position these components. LEVEL OF EVIDENCE: Level III Prospective diagnostic case controlled study. PMID- 25129706 TI - Blade-plate fixation for distal femoral fractures: a case-control study. AB - BACKGROUND: The blade-plate is the earliest of the contemporary internal fixation devices introduced for distal femoral fractures. The recent development of dedicated, fixation devices has considerably limited its use. The objective of this study was to evaluate outcomes after blade-plate fixation and after fixation using other devices. HYPOTHESIS: Outcomes after blade-plate fixation are similar to those after condylar screw-plate, distal femoral nail, or locking condylar plate fixation. MATERIAL AND METHODS: We reviewed outcomes after 62 patients managed with blade-plate fixation and included in a multicentre retrospective study (n=57) or a multicentre prospective study (n=5) and we compared them to outcomes after fixation using condylar screw-plates (n=82), distal femoral nail (n=219), or locking condylar plates (n=301). The four groups were comparable for age, gender distribution, occupational status, prevalence of skin wounds, patient related factors, type of accident, and type of fracture. The evaluation relied on the clinical International Knee Society (IKS) score and on radiographs. RESULTS: No significant differences existed across the four groups for operative time, blood transfusion use, complications, need for bone grafting, non-union rate, or IKS score values. The early surgical revision rate for removal of the fixation material was 4% with the blade-plate and 16% with the other three fixation devices (P=0.02). Post-operative fracture deformity was similar in the four groups with, however, a higher proportion of residual malalignment in the screw fixation group. The final anatomic axis was 3.3+/-1.4 degrees with the blade plate versus 2.3+/-3.7 degrees with the other three fixation devices. The blade plate group had few patients with axial malalignment, and the degree of malalignment was limited to 3 degrees of varus and 10 degrees of valgus at the most, compared to 10 degrees and 18 degrees respectively, with the other three fixation devices. CONCLUSION: Despite the now extremely limited use and teaching of blade-plate fixation, as well as the undeniable technical challenges raised by the implantation of this device, the blade-plate is a simple, strong, and inexpensive fixation method. It remains reliable for the fixation of distal femoral fractures. The disfavour into which the blade-plate is currently falling is not warranted. LEVEL OF EVIDENCE: III, case-control study. PMID- 25129707 TI - Application of electrochemical technology for removing petroleum hydrocarbons from produced water using lead dioxide and boron-doped diamond electrodes. AB - Although diverse methods exist for treating polluted water, the most promising and innovating technology is the electrochemical remediation process. This paper presents the anodic oxidation of real produced water (PW), generated by the petroleum exploration of the Petrobras plant-Tunisia. Experiments were conducted at different current densities (30, 50 and 100 mA cm(-2)) using the lead dioxide supported on tantalum (Ta/PbO2) and boron-doped diamond (BDD) anodes in an electrolytic batch cell. The electrolytic process was monitored by the chemical oxygen demand (COD) and the residual total petroleum hydrocarbon [TPH] in order to know the feasibility of electrochemical treatment. The characterization and quantification of petroleum wastewater components were performed by gas chromatography mass spectrometry. The COD removal was approximately 85% and 96% using PbO2 and BDD reached after 11 and 7h, respectively. Compared with PbO2, the BDD anode showed a better performance to remove petroleum hydrocarbons compounds from produced water. It provided a higher oxidation rate and it consumed lower energy. However, the energy consumption and process time make useless anodic oxidation for the complete elimination of pollutants from PW. Cytotoxicity has shown that electrochemical oxidation using BDD could be efficiently used to reduce more than 90% of hydrocarbons compounds. All results suggest that electrochemical oxidation could be an effective approach to treat highly concentrated organic pollutants present in the industrial petrochemical wastewater and significantly reduce the cost and time of treatment. PMID- 25129708 TI - Effects of dietary wheat bran arabinoxylans on cholesterol metabolism of hypercholesterolemic hamsters. AB - The aim of the present study is to investigate the effects of dietary wheat bran arabinoxylans (AXs) on cholesterol metabolism in hypercholesterolemic hamsters. The hamsters were divided into 3 groups and fed the experimental diets containing AXs or oat beta-glucan at a dose of 5 g/kg for 30 days. As the results, the AXs lowered plasma total cholesterol and LDL-cholesterol concentrations, and increased excretions of total lipids, cholesterol and bile acids, as well as oat beta-glucan. The AXs reduced the activity of 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase, and increased the activity of cholesterol 7-alpha hydroxylase (CYP7A1) in liver. Moreover, the AXs increased propionate and the total short-chain fatty acids (SCFAs) concentrations. These results indicated that dietary AXs reduced the plasma total cholesterol and LDL-cholesterol concentrations by promoting the excretion of fecal lipids, regulating the activities of HMG-CoA reductase and CYP7A1, and increasing colonic SCFAs in hamsters. PMID- 25129709 TI - A novel method to estimate the stiffness of carbohydrate polyelectrolyte polymers based on the ionic strength dependence of zeta potential. AB - Polysaccharides have received a great deal of attention from, for example, the food, cosmetic and pharmaceutical industries. Their conformations (flexibility/stiffness) span a wide range of conformational flexibilities with large hydrated volumes, these properties are important in relation to polysaccharide structure-function relationships. Perhaps the simplest parameter available to estimate the dilute solution conformation of polysaccharides is the Smidsrod-Haug stiffness parameter (B) where the stiffness of polyelectrolytes can be estimated by measuring the intrinsic viscosity at a number of different ionic strengths. In this paper we propose an alternative method for estimating the Smidsrod-Haug stiffness parameter (B) using the ionic strength dependency of zeta potential. For this purpose we have studied a number of different polysaccharides. PMID- 25129710 TI - Synergistic effects of mixed salt on the gelation of kappa-carrageenan. AB - The effect of the addition of calcium or sodium ions on the potassium induced gelation of kappa-carrageenan (kappa-car) is investigated using oscillatory shear rheology and turbidimetry. Both the gelation kinetics and the steady state shear moduli are investigated. Gelation in mixed salt solutions is compared with that in pure potassium and calcium solutions. It is shown that the elastic shear modulus increases with increasing pure KCl concentration, but decreases with increasing pure CaCl2 concentration. In mixed salts, gelation of kappa-car is induced by potassium and addition of CaCl2 leads to an increase of the elastic modulus with increasing CaCl2 concentration. kappa-Car gelled at low mixed salt concentrations for which it remained liquid in pure salt. At equivalent ionic strengths, the effect of adding NaCl on potassium induced gelation is much weaker. In pure KCl solutions, kappa-car gels are transparent, but in pure CaCl2 they become increasingly turbid with increasing CaCl2 concentration. The turbidity of gels formed in mixed salts is intermediate. PMID- 25129711 TI - The excreted polysaccharide of Pleurotus eryngii inhibits the foam-cell formation via down-regulation of CD36. AB - Previous study has verified the polysaccharide from the fruiting body of Pleurotus eryngii (PEPE) is capable of decreasing the lipid content in both of cell-line and mouse model. However, little is known about underlying mechanisms and whether this bioactive polysaccharide exists in submerged culture. Here, we verified the excreted polysaccharides EP and EP-1 from submersion culture of P. eryngii have the remarkable inhibitory effects on lipid accumulation in macrophage-derived foam cells. Structure analysis indicates EP-1 consists of D types of glucose, galactose and mannose with the main beta(1 -> 3)-glucan glycosidic linkage branched at O-6 by alpha-D-glucose while EP digested by beta 1,3-glucanase fails to decrease the lipid accumulation, suggesting that the special structure is essential for its function. Expression analysis suggests that EP is able to cause the down-regulation of the scavenger receptor-CD36 on both transcription and protein levels. Most importantly, EP can be obtained by fermentation in a mass-production. PMID- 25129712 TI - Thermo-mechanical and hydrophilic properties of polysaccharide/gluten-based bioplastics. AB - The influence of adding different polysaccharides (locust bean gum, LBG; methyl cellulose, MC; and carboxymethyl cellulose, CMC) to gluten-based biodegradable polymeric materials was assessed in this work. Gluten/polysaccharide/plasticiser bioplastics were prepared at different polysaccharide concentrations (0-4.5%) and pH values by mixing in a two-blade counter-rotating batch mixer (at 25 degrees C under adiabatic conditions) and thermomoulding at 9MPa and 130 degrees C. Bioplastic probes were evaluated through dynamic mechanical thermal analysis, tensile strength and water absorption capacity tests. Results pointed out that a moderate enhancement of the network structure may be achieved by adding polysaccharide at a pH close to the protein isoelectric point (pH 6), which also conferred a further thermosetting capacity to the system. Moreover, the addition of MC and CMC was found to significantly enhance material elongation properties. However, the presence of charges induced by pH leaded to a higher incompatibility between the polysaccharide and protein domains forming the composite. The pH value played a relevant role in the material water absorption, which significantly increased under acidic or basic conditions (particularly at pH 3). PMID- 25129713 TI - Modification of carboxymethyl cellulose grafted with collagen peptide and its antioxidant activity. AB - Carboxymethyl cellulose used in wounds has little antioxidant capacity. The aim of the present study was to improve the scavenging ability of carboxymethyl cellulose by modified with collagen peptide. The reaction conditions have been optimized by varying mass ratio of collagen peptide to carboxymethyl cellulose, temperature and reaction time. Antioxidant activities of carboxymethyl cellulose derivatives (CMCC) were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, superoxide radicals and the reducing power. The effects of concentration, degree of substitution (DS) and molecular weight on three different radicals scavenging activity and reducing power were examined. Methylthiazol tetrazolium (MTT) assay was used to evaluate the fibroblasts cells cytotoxicity of CMCC. Results showed that the scavenging effects of CMCC increased with the increasing of DS and concentration. This product of CMCC possesses a distinct antioxidant capacity on radicals. PMID- 25129714 TI - Synthesis and surface modification of polyurethanes with chitosan for antibacterial properties. AB - Surface modification and providing antibacterial properties to the materials or devices are getting great attention especially in the last decades. In this study, polyurethane (PU) films were prepared by synthesizing them in medical purity from toluene diisocyanate and polypropylene ethylene glycol without using any other ingredients and then the film surfaces were modified by covalent immobilization of chitosan (CH) which has antibacterial activity. CH immobilized PU films (PU-CH) were found to be more hydrophilic than control PU films. Electron Spectroscopy for Chemical Analysis (ESCA) and Atomic Force Microscopy (AFM) analyses showed higher nitrogen contents and rougher surface topography for PU-CH compared to PU films. Modification with CH significantly increased antibacterial activity against Gram positive (Staphylococcus aureus) and Gram negative (Pseudomonas aeruginosa) bacteria. It was observed that the number of bacteria colonies were less about 10(2)-10(5) CFU/mL and number of attached viable bacteria decreased significantly after CH modification of PU films. PMID- 25129715 TI - Transglycosylation reactions between galactomannans and arabinogalactans during dry thermal treatment. AB - Aiming to investigate the possible occurrence of transglycosylation reactions between galactomannans and side chains of arabinogalactans during coffee roasting, mixtures of beta-(1 -> 4)-D-mannotriose and alpha-(1 -> 5)-L arabinotriose were subjected to dry thermal treatments at 200 degrees C. Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis allowed identifying polysaccharides composed by pentose and hexose residues with a degree of polymerization up to 18 residues. Methylation analysis showed the occurrence of new types of glycosidic linkages in all thermally treated mixtures, as well as the occurrence of terminally and 5-linked ribose, possibly formed from arabinose isomerization. Also, xylose and lyxose were identified and proposed to be formed from mannose. These results support the occurrence of transglycosylation reactions promoted by roasting involving both oligosaccharides in the starting mixtures, resulting in arabinan and mannan chimeric polysaccharides. These structural features were also found in roasted coffee polysaccharide samples. PMID- 25129716 TI - Xylan-cellulose films: improvement of hydrophobicity, thermal and mechanical properties. AB - Xylan-rich hemicellulose from corn cob has been used for new material elaboration. Commercial cellulose was used as reinforcement in different percentages to improve properties of the films. Two types of composites were elaborated by solvent casting. Hydrophilic films, composed by bleached hemicellulose (BH), unmodified cellulose and glycerol as plasticizer, and hydrophobic films formed by acetylated bleached hemicellulose (BAH) and acetylated cellulose. The degree of substitution of BAH was 1.8 and acetylated cellulose presented a degree of substitution of 0.54. Thermal and mechanical properties of films were analyzed. A significant improvement was observed in the thermal behavior of hydrophobic films (Tmax ~ 368 degrees C) respect to hydrophilic films (Tmax ~ 300 degrees C). Although the addition of cellulose clearly increase the properties of both type of films, hydrophobic films (Young's modulus ~ 2300 MPa, strength ~ 44.1MPa, strain at break ~ 5.7%) showed better mechanical properties than hydrophilic films (Young's modulus ~ 3 MPa, strength ~ 3.3 MPa, strain at break ~ 5.3%). PMID- 25129717 TI - Purification, characterization and immunomodulatory effects of Plantago depressa polysaccharides. AB - Four purified polysaccharide fractions from seeds of Plantago depressa (PDSP-1, PDSP-2, PDSP-3 and PDSP-4) were obtained by isolation and purification using DEAE 52 cellulose and Sephacryl S-400 HR chromatography. Basic physicochemical properties including molecular weight, chemical composition, FT-IR and glycosidic linkage of these fractions were investigated. They seemed to be homogeneous acidic protein-bound heteropolysaccharides with high molecular weight of over 1000 kDa and contained a lot more beta-type glycosidic linkages than alpha-type. PDSP-3 mainly contained mannose, arabinose and fucose, and the others were rich in arabinose, fucose and galacturonic acid. The immunomodulatory effects of them were assessed by splenocyte proliferation index and production of NO and TNF alpha from macrophages. They all showed significant immunomodulatory activities, and PDSP-3 presented the strongest effect. Their observed differences in biological activities were probably due to their structure differences. And monosaccharide compositions, linkage types and molecular weight may affect their immunomodulatory activities. PMID- 25129718 TI - (1 -> 3)-beta-D-Glucan nanofibers from paramylon via electrospinning. AB - (1 -> 3)-beta-D-Glucans of paramylon from Euglena gracilis were dissolved in concentrated formic acid and electrospinning was conducted using a newly designed setup. The diameter of the as-spun fibers ranged from 0.05 to 1 MUm, and most of the fibers were straight and aligned parallel to two arbitrary fins (electrodes). By polarized optical microscopy, we determined that the anisotropic texture of the fibers was indicative of parallel alignment of the molecular chains to the fiber axis. The wide-angle X-ray scattering curve for the fibers showed amorphous halo scattering in spite of the high crystallinity of starting paramylon powder. PMID- 25129719 TI - Physicochemical characteristics of polysaccharide conjugates prepared from fresh tea leaves and their improving impaired glucose tolerance. AB - Hot-water extracts were prepared from fresh tea leaves and fractionated by DEAE cellulose DE-52 column chromatography to yield one unexplored polysaccharide conjugate fraction TPC-L (tea polysaccharide conjugates). Chemical components, molecular weight and its distribution, water vapor sorption properties, zeta potentials and optical characteristics of TPC-L were investigated. As compared with injured cell group, the two dosages of TPC-L (150 and 300 MUg/mL) were discovered to possess remarkably protective effect on human umbilical vein endothelial cells against impairments induced by high glucose in a dose-dependent manner (p < 0.05, p < 0.001, respectively). Compared with group NC (normal control), the ingestion of 40 mg/kg of TPC-L could significantly reduce blood glucose levels of normal mice ingesting starch, and significant difference of AUC (area under the curve of blood glucose) and DeltaAUC (p < 0.05, p < 0.01) at the postprandial time point of 0.5 and 1.0 h were observed. The three dosages of TPC L (10, 40 and 160 mg/kg) did not significantly lower postprandial blood glucose levels of normal mice ingesting glucose. TPC-L could improve starch tolerance to prevent impaired glucose tolerance (IGT) from developing into diabetes as well as protective effects on HUVE cells against impairments induced by high glucose It was suggested that TPC-L improved IGT through its capability of inhibition on digestive enzymes. PMID- 25129720 TI - Structures of octenylsuccinylated starches: effects on emulsions containing beta carotene. AB - Starches with different amylopectin contents and different molecular sizes prepared using acid hydrolysis were hydrophobically modified using octenylsuccinic anhydride (OSA). The OSA-modified starches were used as surfactants to stabilize emulsions of beta-carotene and canola oil dispersed in water. The objective of this study is to investigate the relationship between starch molecular structure and the chemical stability of the emulsified beta carotene, as well as the colloidal stability of emulsion droplets during storage. The oil droplet size in emulsions was smaller when starch had (a) lower hydrodynamic volume (Vh) and (b) higher amylopectin content. The oxidative stability of beta-carotene was similar across samples, with higher results at increased amylopectin content but higher Vh. Steric hindrance to coalescence provided by adsorbed OSA-modified starches appears to be improved by more rigid molecules of higher degree of branching. PMID- 25129721 TI - Assessment of the physical, mechanical, and moisture-retention properties of pullulan-based ternary co-blended films. AB - Multi-component substances made through direct blending or blending with co drying can form films on the surfaces of intermediate moisture foods (IMFs), which help retain moisture and protect food texture and flavor. An IMF film system based on pullulan, with glycerol serving as the plasticizer, was studied using alginate and four different types of polysaccharides (propyleneglycol alginate, pectin, carrageenan, and aloe polysaccharide) as the blend-modified substances. The physical, mechanical, color, transparency, and moisture-retention properties of the co-blended films with the polysaccharides were assessed. A new formula was established for the average moisture retention property, water barrier, tensile strength, elongation at break, and oxygen barrier property of the ternary co-blended films using the Design Expert software. The new model established for moisture content measurement used an indirect method of film formation on food surfaces by humectants, which should expedite model validation and allow a better comprehension of moisture transfer through edible films. PMID- 25129722 TI - CTAB turbidimetric method for assaying hyaluronic acid in complex environments and under cross-linked form. AB - The cetyltrimethylammonium bromide turbidimetric method (CTM) has been developed to quantify the hyaluronic acid (HA) in complex media to overcome the lack of selectivity and specificity of the standard carbazole method. The objective of this work is to assess the potential application of CTM to determine HA concentration. Factors such as duration of incubation, linearity range, HA size and form (natural linear HA or cross linked HA), pH and ionic environment impact were investigated. The incubation time was set to 10 min and the calibration curve was linear up to 0.6 g L(-1). The quantitative method was relevant whatever the HA size and form, and also for a wide range of conditions. The robustness of the CTM added to its high specificity and simplicity demonstrated that the CTM is a valuable method that would be an interesting substitute to the carbazole assay for HA quantification. PMID- 25129723 TI - Immunomodulation of human macrophages and myeloid cells by 2-substituted (1-3) beta-D-glucan from P. parvulus 2.6. AB - beta-glucans produced by eukaryotic cells and by microorganisms are known to modulate immune responses by affecting macrophage activation. Here, we have investigated the effect of purified 2-substituted (1-3)-beta-D-glucan, produced by either Pediococcus parvulus 2.6 or Lactococcus lactis NZ9000[pNGTF], on the effector functions of human PMA-differentiated THP-1 cells and M1 pro inflammatory monocyte-derived macrophages. The results reveal that this kind of beta-D-glucan activates macrophages and has an anti-inflammatory effect. PMID- 25129724 TI - Antioxidant and immunological activities of polysaccharides from Gentiana scabra Bunge roots. AB - Two polysaccharide fractions, GSP I-a and GSP II-b, were isolated from Gentiana scabra Bunge roots. Both GSP I-a and GSP II-b comprised seven monosaccharides: fructose, mannose, rhamnose, galacturonic acid, glucose, galactose, and fucose. Ultraviolet and infrared analyses show that GSP I-a and GSP II-b are proteoglycans. In vitro evaluation of the antioxidant activity suggests that GSP I-a and GSP II-b scavenge 1,1-diphenyl-2-picrylhydrazyl radicals. However, the scavenging activity of the latter is stronger than that of the former. GSP I-a and GSP II-b have relatively low reducing powers and scavenging activities toward superoxide anions and hydroxyls. GSP I-a and GSP II-b significantly increase lymphocyte proliferation when lipopolysaccharide is used as a mitogen for lymphocytes, but only GSP I-a can significantly increase lymphocyte proliferation within the test-dosage range when concanavalin A is used as a mitogen. PMID- 25129725 TI - Surface-initiated atom transfer radical polymerization from chitin nanofiber macroinitiator film. AB - This paper reports the preparation of chitin nanofiber-graft-poly(2-hydroxyethyl acrylate) (CNF-g-polyHEA) films by surface-initiated atom transfer radical polymerization (ATRP) of HEA monomer from a CNF macroinitiator film. First, a CNF film was prepared by regeneration from a chitin ion gel with an ionic liquid. Then, acylation of the CNF surface with alpha-bromoisobutyryl bromide was carried out to obtain the CNF macroinitiator film having the initiating moieties (alpha bromoisobutyrate group). The surface-initiated graft polymerization of HEA from the CNF macroinitiator film by ATRP was performed to produce the CNF-g-polyHEA film. The IR, XRD, and SEM measurements of the resulting film indicated the progress of the graft polymerization of HEA on surface of CNFs. The molecular weights of the grafted polyHEAs increased with prolonged polymerization times, which affected the mechanical properties of the films under tensile mode. PMID- 25129726 TI - True molecular solutions of natural cellulose in the binary ionic liquid containing solvent mixtures. AB - Evidence is presented for the first time of true molecular dissolution of cellulose in binary mixtures of common polar organic solvents with ionic liquid. Cryogenic transmission electron microscopy, small-angle neutron-, X-ray- and static light scattering were used to investigate the structure of cellulose solutions in mixture of dimethyl formamide and 1-ethyl-3-methylimidazolium acetate. Structural information on the dissolved chains (average molecular weight ~ 5 * 10(4)g/mol; gyration radius ~ 36 nm, persistence length ~ 4.5 nm), indicate the absence of significant aggregation of the dissolved chains and the calculated value of the second virial coefficient ~ 2.45 * 10(-2)mol ml/g(2) indicates that this solvent system is a good solvent for cellulose. More facile dissolution of cellulose could be achieved in solvent mixtures that exhibit the highest electrical conductivity. Highly concentrated cellulose solution in pure ionic liquid (27 wt.%) prepared according to novel method, utilizing the rapid evaporation of a volatile co-solvent in binary solvent mixtures at superheated conditions, shows insignificant cellulose molecular aggregation. PMID- 25129727 TI - Radiolytically depolymerized sodium alginate improves physiological activities, yield attributes and composition of essential oil of Eucalyptus citriodora Hook. AB - Eucalyptus citriodora Hook. is highly valued for its citronellal-rich essential oil (EO) extracted from its leaves. Hence, escalated EO production of eucalyptus is the need of hour. Marine polysaccharides (sodium alginate) are processed through gamma radiation of particular intensity, to obtain the irradiated sodium alginate (ISA). A pot experiment was conducted to study the effect of foliar application of ISA on growth, biochemical, physiological, EO yield and composition of E. citriodora. The treatments were applied as: foliar spray of deionized water only (control), seed soaked with ISA (90 mg L(-1)) and foliar spray of ISA with 30, 60, 120 and 240 mg L(-1). The treatment 6 (spray of ISA at 120 mg L(-1)) showed the highest value for most of the parameters studied. It also enhanced the EO content (33.3%), EO yield (86.7%), citronellal content (63.4%) and citronellal yield (205.5%) as compared to the control. PMID- 25129728 TI - From algal polysaccharides to cyclodextrins to stabilize a urease inhibitor. AB - N-Butyl-phosphorotriamide (NBPT) is a fertilizer widely used for its urease inhibiting properties. Nevertheless, formulations currently commercialized are complex and do not avoid severe decrease of activity due to the low stability of the bioactive compound under acidic conditions. According to its structure, NPBT was thought to be able to interact with both polar additives, by its phosphoramide function, and hydrophobic ones, through its alkyl chain. In this context, and in order to simplify formulations of this bioactive compound, a panel of natural polysaccharides was studied, including starch, beta-(1,3) glucans, carraghenans and alginates. We also used cyclodextrins, characterized the most stable inclusion complex with alpha-cyclodextrin and evaluated the stability of NBPT thus protected against hydrolysis under acidic conditions. PMID- 25129729 TI - Effects of chitosan on oxidative stress and related factors in hemodialysis patients. AB - In recent world-wide studies, chitosans were tested as a dietary supplement for inhibiting the absorption of certain lipids and bile acids. We previously demonstrated the antioxidative and renoprotective potential of chitosan supplementation in chronic renal failure using 5/6 nephrectomized rats. In this study, we report the effects of chitosan on oxidative stress and related factors in hemodialysis patients. The ingestion of chitosan over a 12-week period resulted in a significant decrease in serum indoxyl sulfate and phosphate levels, compared with the levels prior to the start of the study. The ingestion of chitosan also resulted in a lowered ratio of oxidized to reduced albumin and a decrease in the level of advanced oxidized protein products. In in vitro studies, chitosan solutions were found to bind 38.5% of the indoxyl sulfate and 17.8% of the phosphate, respectively. Further, the oxidized albumin ratio was correlated with serum indoxyl sulfate levels in vivo. These results suggest that the ingestion of chitosan results in a significant reduction in the levels of pro oxidants, which include uremic toxins, in the gastrointestinal tract, thereby inhibiting the subsequent development of oxidative stress in the systemic circulation. In addition, the long-term ingestion of chitosan has the potential for use in treating hyperphosphatemia in hemodialysis patients. PMID- 25129730 TI - Light-induced surface graft polymerizations initiated by an anthraquinone dye on cotton fibers. AB - Anthraquinone and its derivatives could serve as photo-sensitizers and generate radicals and reactive oxygen species in polymers under exposure of UVA or day light. Such a property was utilized in development of novel light-induced surface radical graft polymerizations on cotton fibers that were dyed with an anthraquinone derivative, 2-ethylanthraquinone. Several functional monomers were directly grafted onto the dyed cotton fibers upon UVA exposure. The chemical and morphological structures and thermal properties of the grafted fibers were confirmed and characterized by Fourier transform infrared spectrometer (FTIR), scanning electron microscope (SEM) and thermal gravimetric analysis (TGA). Reaction conditions including concentrations of the photosensitizer, the amount of monomers, as well as UVA irradiation time could influence grafting efficiencies. More interestingly, the surface graft polymerization did not significantly change the light active functions of the agent, evidenced by the light-active antimicrobial functions of the grafted fibers. PMID- 25129731 TI - Improvement of polyvinyl alcohol properties by adding nanocrystalline cellulose isolated from banana pseudostems. AB - Cellulose nanocrystals (CNCs) isolated from banana pseudostems fibers (BPF) of the Pacovan variety were used as fillers in a polyvinyl alcohol (PVOH) matrix to yield a nanocomposite. The fibers from the external fractions of the BPF were alkaline bleached and hydrolyzed under acidic conditions (H2SO4 62% w/w, 70 min, 45 degrees C) to obtain CNCs with a length (L) of 135.0 +/- 12.0 nm and a diameter (D) of 7.2 +/- 1.9 nm to yield an aspect ratio (L/D) of 21.2. The CNCs were applied to PVOH films at different concentrations (0%, 1%, 3%, and 5% w/w, dry basis). With higher concentrations of CNCs, the water-vapor barrier of the films increased, while the optical properties changed very little. Increasing the concentration of the CNCs up to 3% significantly improved the mechanical properties of the nanocomposite. PMID- 25129732 TI - Fucosylated chondroitin sulfate diversity in sea cucumbers: a review. AB - Fucosylated chondroitin sulfate (FucCS) is structurally distinct glycosaminoglycans found from the sea cucumber body wall consisted of chondroitin sulfate type backbone with attached sulfated or non-sulfated fucose side chain. Structurally this compound plays an important role in maintaining the body wall integrity and possesses a wide spectrum of biological activities. Recently several glycosaminoglycans' structures have been solved to elucidate its physicochemical activity. The purpose of this review paper is to elaborate existing structural properties and functions, reporting over 30 years and systematically discussion herein. PMID- 25129733 TI - Validation of lignocellulosic biomass carbohydrates determination via acid hydrolysis. AB - This work studied the two-step acid hydrolysis for determining carbohydrates in lignocellulosic biomass. Estimation of sugar loss based on acid hydrolyzed sugar standards or analysis of sugar derivatives was investigated. Four model substrates (starch, holocellulose, filter paper and cotton) and three levels of acid/material ratios (7.8, 10.3 and 15.4, v/w) were studied to demonstrate the range of test artifacts. The method for carbohydrates estimation based on acid hydrolyzed sugar standards having the most satisfactory carbohydrate recovery and relative standard deviation. Raw material and the acid/material ratio both had significant effect on carbohydrate hydrolysis, suggesting the acid to have impacts beyond a catalyst in the hydrolysis. Following optimal procedures, we were able to reach a carbohydrate recovery of 96% with a relative standard deviation less than 3%. The carbohydrates recovery lower than 100% was likely due to the incomplete hydrolysis of substrates, which was supported by scanning electron microscope (SEM) images. PMID- 25129734 TI - Crosslinking chitosan into H3PO4/HNO3-NANO2 oxidized cellulose fabrics as antibacterial-finished material. AB - The primary hydroxyl groups on C6 position in glucose units of cellulose with H3PO4/HNO3-NaNO2 mediated oxidation produced monocarboxy cellulose and binding sites, subsequent amide reaction with chitosan solution to obtain chitosan crosslinked cotton fabrics. Scanning electron microscope and FT-IR spectroscopy were used to detect the fiber morphology and chemical bonding between chitosan and oxidized cellulose, respectively. The influences of H3PO4/HNO3-NaNO2 oxidation and chitosan treatment on physical properties of cotton fabrics were examined by determining carboxyl content, weight loss and mechanical properties of fabrics, as well as chitosan content in the composite fabrics. Antibacterial performance of chitosan-cellulose fabrics against Escherichia coli and Staphylococcus aureus was evaluated. As a result, chitosan was bonded into cotton fiber via the amido bond of CN formed between amino groups of chitosan and carboxyl groups on oxidized cellulose, and these resultant chitosan-cotton fabrics showed high antimicrobial activity and excellent antibacterial washing durability. PMID- 25129735 TI - Green synthesis of silver and copper nanoparticles using ascorbic acid and chitosan for antimicrobial applications. AB - Silver and copper nanoparticles were produced by chemical reduction of their respective nitrates by ascorbic acid in the presence of chitosan using microwave heating. Particle size was shown to increase by increasing the concentration of nitrate and reducing the chitosan concentration. Surface zeta potentials were positive for all nanoparticles produced and these varied from 27.8 to 33.8 mV. Antibacterial activities of Ag, Cu, mixtures of Ag and Cu, and Ag/Cu bimetallic nanoparticles were tested using Bacillus subtilis and Escherichia coli. Of the two, B. subtilis proved more susceptible under all conditions investigated. Silver nanoparticles displayed higher activity than copper nanoparticles and mixtures of nanoparticles of the same mean particle size. However when compared on an equal concentration basis Cu nanoparticles proved more lethal to the bacteria due to a higher surface area. The highest antibacterial activity was obtained with bimetallic Ag/Cu nanoparticles with minimum inhibitory concentrations (MIC) of 0.054 and 0.076 mg/L against B. subtilis and E. coli, respectively. PMID- 25129736 TI - Amberlyst 15 as a new and reusable catalyst for the conversion of cellulose into cellulose acetate. AB - The acetylation of cellulose using sulfonated Amberlyst 15 as a new and reusable catalyst was investigated. Optimization of the acetylation process was carried out by variation in the amount of added catalyst, acetic acid, and acetic anhydride as well as the reaction conditions, which includes reaction time and reaction medium. Cellulose acetate, with a degree of substitution (DS) value of 2.38 and yield of 54.1%, was obtained under the optimized conditions and characterized using Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis-derivative thermogravimetry (TGA-DTG), and differential scanning calorimetry (DSC). The sulfonated polymer catalyst could be easily recovered by centrifugation after acetylation. Both the fresh and recovered catalysts were characterized by means of FTIR, TGA-DTG, DSC, and scanning electron microscopy (SEM), and the recovered catalyst could be successfully reused without further treatment. It was found that Amberlyst 15 possessed excellent catalytic stability, no significant changes in the DS values, and consistent yields of cellulose acetate observed over four reaction cycles. PMID- 25129737 TI - Starch granules as a vehicle for the oral administration of immobilized antigens. AB - Microparticles of diverse compositions are often used as carriers for interesting antigens. In this work, we propose the use of natural microparticulated starch as a vehicle for antigens. The proposed system is composed of raw starch microparticles and a starch-binding domain that when fused to another protein, allows for a stable protein immobilization onto the granule surface. To demonstrate the use of starch as an antigen carrier, a fusion combining fragment C of the tetanus toxin with the starch-binding domain was adsorbed to starch and administered orally to mice in two different doses and, importantly, without the use of any adjuvant. The results showed that the system allows the induction of specific antibodies; moreover mice given this immobilized protein presented a delay in the onset of tetanus symptoms compared to mice administered the non immobilized protein. The study outlines the viability of this immobilization system as an antigen and protein carrier. PMID- 25129738 TI - Inducing PLA/starch compatibility through butyl-etherification of waxy and high amylose starch. AB - In this study, waxy and high amylose starches were modified through butyl etherification to facilitate compatibility with polylactide (PLA). Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy and wettability tests showed that hydrophobic butyl-etherified waxy and high amylose starches were obtained with degree of substitution values of 2.0 and 2.1, respectively. Differential scanning calorimetry, tensile testing, and scanning electron microscopy (SEM) demonstrated improved PLA/starch compatibility for both waxy and high amylose starch after butyl-etherification. The PLA/butyl-etherified waxy and high amylose starch composite films had higher tensile strength and elongation at break compared to PLA/non-butyl-etherified composite films. The morphological study using SEM showed that PLA/butyl-etherified waxy starch composites had a more homogenous microstructure compared to PLA/butyl-etherified high amylose starch composites. Thermogravimetric analysis showed that PLA/starch composite thermal stability decreased with starch butyl-etherification for both waxy and high amylose starches. This study mainly demonstrates that PLA/starch compatibility can be improved through starch butyl-etherification. PMID- 25129739 TI - Electrosprayed inulin microparticles for microbiota triggered targeting of colon. AB - Inulin, a naturally occurring polysaccharide, was acetylated to make it processable by electrospraying, a facile and single step method for microparticle fabrication. Electrospraying process parameters were optimized for fabrication of spherical and monodisperse indomethacin (IDM) loaded inulin acetate (INA) microparticles. The apparent entrapment efficiency of IDM was determined to be 100%, whereas working encapsulation efficiency was estimated to be 35.39 +/- 1.63%. Differential scanning calorimetry and X-ray diffraction analysis confirmed molecular dispersion of IDM in an amorphous state within the INA matrix. Finally, the results from in vitro release study performed in simulated gastro-intestinal fluids demonstrated that IDM was released only in simulated colonic fluid that contained inulinase. Therefore, this study demonstrates that acetylation of inulin does not alter its susceptibility to inulinase and that microparticles fabricated from INA can be developed as a colon targeting drug delivery system. PMID- 25129741 TI - Characterization of an amylose-graft-poly(n-butyl methacrylate) copolymer obtained by click chemistry by EPR and SS-NMR spectroscopies. AB - We present an investigation of the main chemical and physico-chemical properties of a graft copolymer of amylose and poly(n-butyl methacrylate), Am-g-PBMA, amphiphilic and able to self-assemble in water, prepared by coupling end azide functionalized PBMA and alkyne-functionalized amylose under convenient click conditions. A deep knowledge of these properties is necessary in the perspective of real applications of the copolymer. To this aim we combined a basic characterization through FT-IR, TGA, ICP-OES and SEM with an extensive EPR and Solid State NMR investigation. It was possible to characterize the main structural and dynamic properties of Am-g-PBMA and highlight the presence of residual copper (Cu(II)) from the catalyst, even after an extensive purification procedure. We could identify two main species of Cu(II): Cu(II) complexes coordinated to the N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA) ligand from the catalyst and to the copolymer triazole nitrogens and multi-nuclear or clustered Cu(II) species likely coordinated to amylose hydroxyl groups. PMID- 25129740 TI - Alginate based hybrid copolymer hydrogels--influence of pore morphology on cell material interaction. AB - Alginate based hybrid copolymer hydrogels with unidirectional pore morphology were prepared to achieve synergistic biological performance for cardiac tissue engineering applications. Alginate based hybrid copolymer (ALGP) were prepared using alginate and poly(propylene fumarate) (HT-PPF) units. Different hybrid bimodal hydrogels were prepared by covalent crosslinking using poly(ethylene glycol diacrylate) and vinyl monomer viz acrylic acid, methyl methacrylate, butyl methacrylate and N-N'-methylene-bis-acrylamide and ionic crosslinking with calcium. The morphologically modified hydrogels (MM-hydrogels) with unidirectional elongated pores and high aspect ratio were prepared. MM-hydrogels favour better mechanical properties; it also enhances cell viability and infiltration due to unidirectional pores. However, the crosslinkers influence the fibroblast infiltration of these hydrogels. Synthesis of collagen and fibroblast infiltration was greater for alginate copolymer crosslinked with poly(ethylene glycol diacrylate-acrylic acid (ALGP-PA) even after one month (288%). This hybrid MM-hydrogel promoted cardiomyoblast growth on to their interstices signifying its potent applications in cardiac tissue engineering. PMID- 25129742 TI - Nanostructured membranes based on native chitin nanofibers prepared by mild process. AB - Procedures for chitin nanofiber or nanocrystal extraction from Crustaceans modify the chitin structure significantly, through surface deacetylation, surface oxidation and/or molar mass degradation. Here, very mild conditions were used to disintegrate chitin fibril bundles and isolate low protein content individualized chitin nanofibers, and prepare nanostructured high-strength chitin membranes. Most of the strongly 'bound' protein was removed. The degree of acetylation, crystal structure as well as length and width of the native chitin microfibrils in the organism were successfully preserved. Atomic force microscopy and scanning transmission electron microscopy, showed chitin nanofibers with width between 3 and 4 nm. Chitin membranes were prepared by filtration of hydrocolloidal nanofiber suspensions. Mechanical and optical properties were measured. The highest data so far reported for nanostructured chitin membranes was obtained for ultimate tensile strength, strain to failure and work to fracture. Strong correlation was observed between low residual protein content and high tensile properties and the reasons for this are discussed. PMID- 25129743 TI - Bio-inspired Aloe vera sponges for biomedical applications. AB - Chemical composition and biological properties of Aloe vera (AV), a tropical plant, explain its potential use for cosmetic, nutritional and biomedical applications. AV gel present in AV leaves is rich in several compounds, nutrients and polysaccharides. This work proposes using AV gel complex structure and chemical composition, associated with freeze-drying, to produce sponges. To increase the structures stability in aqueous media, a thin coating of gellan gum (GG), was applied onto AV gel. AV-based sponges showed a heterogeneous porous formation, interconnected pores and good porosity (72-77%). The coating with a GG layer onto AV influenced the stability, swelling behavior and mechanical properties of the resulting sponges. Moreover, sponges provided the sustained release of BSA-FTIC, used as a model protein, over 3 weeks. Also, in vitro cell culture studies evidenced that sponges are not cytotoxic for a mouse fibroblast like cell line. Therefore, developed AV-based sponges have potential use in biomedical applications. PMID- 25129745 TI - Preparation of aligned porous chitin nanowhisker foams by directional freeze casting technique. AB - Structured biofoams with aligned porous structures were fabricated from nanosized chitin by employing a directional freeze-casting technique. The effects of the freezing conditions and slurry formulation on nanochitin foam morphology were investigated. The morphology of obtained foams was characterized using scanning electron microscopy (SEM). It was found that the pore structure of the obtained foams was a likewise of the ice crystals formed during the directional freezing. The results indicate that directional freeze-casting protocol can significantly influence the morphological features and microstructures of the obtained biofoams which could have numerous applications, including engineered carriers, scaffolds, filters and specifically as a template for potential multi-layered composites after infusion with a second phase. PMID- 25129746 TI - Aqueous counter collision using paired water jets as a novel means of preparing bio-nanofibers. AB - This study involved a detailed investigation of a novel approach to reducing naturally occurring cellulose fibers into nanofibers solely by the use of aqueous counter collision (ACC) without any chemical modification. In this process, equivalent aqueous suspensions of cellulose are ejected from dual nozzles and collide at high speed and pressure. Even a few repetitions of the collision process are sufficient to produce nano-sized fibers dispersed in water. This work compared the ACC nano-pulverization of stable Ibeta-rich and meta-stable Ialpha rich cellulose samples. The ACC method is applicable to various kinds of polymeric materials with hierarchical structures, either natural or synthetic, as a means of preparing aqueous dispersions of nano-sized structures. PMID- 25129744 TI - Enhanced multiparametric hyaluronan degradation for production of molar-mass defined fragments. AB - Hyaluronic acid (HA) is known to serve as a dynamic mediator intervening in many physiological functions. Its specific effect has been repeatedly confirmed to be strongly influenced by the molecular size of hyaluronan fragments. However common technological approaches of HA fragments production have their limitations. In many cases, the final products do not meet the strict pharmaceutical requirements, specifically due to size polydispersity and reaction contaminants. We present novel methodology based on combination of unique incidental ability of the plant-derived protease papain to split the glycosidic bonds and an indispensable advantages of biocompatible macroporous material with incorporated ferrous ions serving as carrier for covalent papain fixation. This atypical and yet unpublished highly efficient multiparametric approach allows enhanced HA fragmentation for easily and safely producing molar-mass-defined HA fragments with narrow size distribution. Native polyacrylamide gel electrophoresis (PAGE) and size exclusion chromatography/multi-angle light scattering (SEC-MALS) confirmed the effectiveness of our multiparametric approach. PMID- 25129747 TI - Durability and synergistic effects of KI on the acid corrosion inhibition of mild steel by hydroxypropyl methylcellulose. AB - The performance of hydroxypropyl methylcellulose (HPMC) as safe corrosion inhibitor for mild steel in aerated 0.5M H2SO4 solution was appraised by weight loss, impedance and polarization measurements. Results indicate that HPMC functions as a good inhibitor in the studied environment and inhibition efficiency increased with increasing concentration of inhibitor and temperature. Time-dependent effect of the inhibition efficiency reveals that inhibition efficiency increased with time up to the fourth day after which it waned, but improved on addition of KI. The synergism parameter evaluated confirmed the synergistic effect of KI and HPMC. Impedance results clearly show that HPMC inhibited the corrosion reaction via adsorption onto the metal/solution interface following Freundlich adsorption isotherm. Polarization results indicate that HPMC acts as a mixed-type inhibitor with predominant cathodic effect. Theoretical study using density functional theory was employed to establish the correlation between the structure (molecular and electronic) and the inhibition efficiency. PMID- 25129748 TI - Chemical studies on the polysaccharides of Salicornia brachiata. AB - A group of 12 polysaccharide extracts were prepared from the tips, stem and roots of an Indian halophyte Salicornia brachiata Roxb. obtained by sequential extractions with cold water (CW), hot water (HW), aqueous ammonium oxalate (OX) and aqueous sodium hydroxide (ALK) solutions. Monosaccharide composition analysis revealed that all the polysaccharide extract samples consisted primarily of rhamnose, arabinose, mannose, galactose, glucose, whereas ribose and xylose were present only in some of the extracts. All the extracts exhibited low apparent viscosity (1.47-2.02 cP) and sulphate and contained no prominent toxic metal ions. Fucose was detected only in OX extract of the roots. These polysaccharides were found to be heterogeneous and highly branched (glycoside linkage analysis, size-exclusion chromatography, (13)C-NMR, FT-IR, circular dichroism and optical rotation data). Physico-chemical analyses of these polysaccharides including uronic acid, sulphate and protein contents were also carried out. This constitutes the first report on the profiling of Salicornia polysaccharides. PMID- 25129749 TI - Modification of pine pulp during oxygen delignification by xylan self-assembly. AB - Self-assembly is a technique of preparing functional materials based on targeted intermolecular interactions involving different macromolecules. In this work, hardwood xylan was disassembled from wood and birch bleached kraft pulp using pressurized hot water extraction (HWX) and cold alkali extraction (CAX), respectively. The extracted biopolymers were characterized using gas chromatography (GC), size exclusion chromatography (SEC) and Fourier transform infrared spectroscopy (FTIR), and subsequently added into an oxygen delignification reactor containing pine kraft pulp. The assembly of xylan-pulp fiber was characterized using advanced time-of-flight secondary ion mass spectrometry (ToF-SIMS) and imaging. The xylan-pine pulp assembly was not significantly removed during the whole elemental chlorine free bleaching sequence or during low consistency refining. Modified fibers had superior mechanical properties compared to the reference pulp. Our concept can be easily applied in the pulp and paper industry, and it opens new possibilities for the utilization of fully bio-based fibers in new materials. PMID- 25129750 TI - Evolution of amylopectin structure in developing wheat endosperm starch. AB - In this study, starches extracted from wheat grains harvested at 7, 14, 28, and 35 days after anthesis (DAA) were used as a means of examining the molecular structure of amylopectin (AP) from developing wheat grain. Scanning electron microscopy of wheat grain cross-sections revealed the presence of endosperm at 7 DAA and contained lenticular-shaped developing large (A-type) granules. From 14 DAA onward, spherical-shaped small (B-type) granules coexisted with large granules in the endosperm. During granule development, the fine structure of AP varied with maturity in both large and small granules. Towards the end of the pre physiological maturity stage (28 DAA), AP in small and large granules had shortest external chain length (ECL), longest internal chain length (ICL) and lowest amount of A-chains. At physiological maturity (35 DAA), these changes in ECL, ICL and amount of A-chains were reversed when compared to 28 DAA. In both large and small granules, the external AP structure was apparently more organized at physiological maturity than at pre-physiological maturity. PMID- 25129751 TI - Structure of clusters and building blocks in amylopectin from developing wheat endosperm. AB - Changes in internal structure of amylopectin (AP) during wheat endosperm development were studied by isolating clusters and building blocks of AP from both large A-type and small B-type starch granules at different maturity stages up to harvest time at 49 days after anthesis (DAA). Clusters isolated from B-type granules had a degree of branching (DB) of 16.5-16.8% and were more tightly branched than those isolated from A-type granules (DB 15.7-16.2%). The degree of polymerization (DP) of the clusters increased in both types of granules during the pre-physiological maturity stage up to 28 DAA. Clusters at maturity were smaller with less branches and building blocks than at the end of the pre maturity stage. It is suggested that this was due to a continuous trimming of the cluster structure after the active period of starch synthesis. Differences were evident between A- and B-type granules with regards to glucan trimming and the type of new chains produced. PMID- 25129753 TI - Synthesis and characterization of cellulose acetate from rice husk: eco-friendly condition. AB - Cellulose acetate was synthesized from rice husk by using a simple, efficient, cost-effective and solvent-free method. Cellulose was isolated from rice husk (RH) using standard pretreatment method with dilute alkaline and acid solutions and bleaching with 2% H2O2. Cellulose acetate (CA) was synthesized successfully with the yield of 66% in presence of acetic anhydride and iodine as a catalyst in eco-friendly solvent-free conditions. The reaction parameters were standardized at 80 degrees C for 300 min and the optimum results were taken for further study. The extent of acetylation was evaluated from % yield and the degree of substitution (DS), which was determined by (1)H NMR and titrimetrically. The synthesized products were characterized with the help modern analytical techniques like FT-IR, (1)H NMR, XRD, etc. and the thermal behavior was evaluated by TGA and DSC thermograms. PMID- 25129752 TI - Stretching properties of xanthan and hydroxypropyl guar in aqueous solutions and in cosmetic emulsions. AB - Filament stretchability of xanthan gum (XG) and hydroxypropyl guar (HPG) was investigated in aqueous solutions (0.125, 0.25, 0.5, 1, 1.2 and 1.5% w/w) and in O/W emulsions using a texture analyzer. Additionally, rheological characterizations were carried out on the systems and shear and oscillation parameters were used to interpret stretching properties. XG solutions exhibited a solid-like behavior with rheological parameters much higher than for HPG one whatever the concentration. Filament stretching values of XG solutions were superior to HPG for concentration below 1% w/w and then became comparable for higher concentrations. No meaningful relationship was found between rheological and stretching values. Synergy was observed for all XG/HPG mixtures at 0.125, 0.25 and 0.5% influencing both the rheological and the filament stretching values. The 25/75 XG/HPG ratio showed the maximum synergistic effect at all concentrations while the filament stretchability was enhanced in a wider range of ratios. XG and HPG did not present the same behavior in emulsions. No clear synergistic effect was observed and XG markedly influenced the emulsion filament stretching. PMID- 25129754 TI - Viscoelastic behavior of maize kernel studied by dynamic mechanical analyzer. AB - The creep recovery, stress relaxation, temperature-dependence and their frequency dependence of maize kernel were determined within a moisture content range of 11.9% to 25.9% (w/w) by using a dynamic mechanical analyzer. The 4-element Burgers model was found to adequately represent the creep behavior of the maize seeds (R(2)>0.97). The 5-element Maxwell model was able to better predict the stress relaxation behavior of maize kernel than the 3-element Maxwell model. The Tg values for the maize kernels decreased with increased moisture content. For example, the Tg values were 114 degrees C and 65 degrees C at moisture content values of 11.9% (w/w) and 25.9% (w/w), respectively. The magnitude of the loss moduli and loss tangent and their rate of change with frequency were highest at 20.7% and lowest at 11.9% moisture contents. The maize kernel structure exhibited A-type crystalline pattern and the microstructure was found to expand with increase in moisture content. PMID- 25129755 TI - Ginsenoside compound K-bearing glycol chitosan conjugates: synthesis, physicochemical characterization, and in vitro biological studies. AB - Ginsenosides are triterpenoids found in Panax ginseng and have a numerous structural, functional, and pharmacological properties. The purpose of this study was to develop hydrophilic polymer functionalized ginsenoside conjugates to enhance water solubility and targeted delivery. To this end, hydrophobic ginsenoside compound K (CK) was covalently conjugated to the backbone of hydrophilic glycol chitosan (GC) through an acid-labile linkage. The resulting GC CK conjugates formed self-assembled spherical nanoparticles in an aqueous solution, and their particles sizes were (296 nm and 255 nm) dependent on the degree of CK substitution. The nanoparticles were stable in the physiological buffer (pH 7.4) over a period of 8 days, whereas they were readily degraded under acidic conditions (pH 5.0) mimicking the intracellular pH-conditions. From in vitro release experiment, it was found that CK released slowly from the self assembled nanoparticles in the physiological buffer (pH 7.4). On the other hand, the release rate of CK was rapidly increased under the acidic condition (pH 5.0). In vitro cytotoxicity assays revealed that GC-CK conjugates exhibited higher cytotoxicity than CK in HT29, and similar cytotoxicity in HepG2, and HT22 cell lines. Moreover, RAW264.7 cells treated with GC-CK maintained good cell viability and exhibited decreased lipopolysaccharide-induced NO production. Taken together, these results suggest that the GC-CK conjugate may be potentially useful as a tumor-specific delivery vehicle. PMID- 25129756 TI - Carboxymethylcellulose film for bacterial wound infection control and healing. AB - Infection control and wound healing profiles of sodium carboxymethylcellulose (SCMC) films were investigated as a function of their anti-bacterial action, physical structures, polymer molecular weights and carboxymethyl substitution degrees. The films were prepared with in vitro polymer/film and in vivo microbe colonized wound healing/systemic infection profiles examined. Adhesive high carboxymethyl substituted SCMC films aided healing via attaching to microbes and removing them from wound. Pseudomonas aeruginosa was removed via encapsulating in gelling low molecular weight SCMC film, whereas Staphylococcus aureus was trapped in tight folds of high molecular weight SCMC film. Incomplete microbe removal from wound did not necessary translate to inability to heal as microbe remnant at wound induced fibroblast migration and aided tissue reconstruction. Using no film nonetheless will cause systemic blood infection. SCMC films negate infection and promote wound healing via specific polymer-microbe adhesion, and removal of S. aureus and P. aeruginosa requires films of different polymer characteristics. PMID- 25129757 TI - Transdermal delivery of 10,11-methylenedioxycamptothecin by hyaluronic acid based nanoemulsion for inhibition of keloid fibroblast. AB - This study designs an alternative transdermal delivery system for 10,11 methylenedioxycamptothecin(MD-CPT) to inhibit keloid. Hyaluronic acid nanoemulsions (HANs) with nano size, negative charge and good stability were prepared as transdermal carriers. The MD-CPT loaded HANs performed desirable skin permeable capacity across human keloid skin and the drug was transferred directly to keloid lesion area. MD-CPT was delivered percutaneously higher than the control group. FITC-HANs could be successfully internalized by keloid fibroblast (KF) and deliver MD-CPT toward nucleus, inhibited the proliferation of KF, while there was no serious toxicity to normal skin fibroblasts. The growth-inhibitory effect was further clarified upon cell cycle regulation, which arrested cells at G1/S and prevented them entry into mitosis. KF gene expression demonstrated plasminogen activator inhibitor-1 (PAI-1) was significantly down-regulated and Smad7 up-regulated, which was beneficial to inhibit keloid. The study demonstrated that as transdermal delivery of MD-CPT by HANs has potential for inhibition of keloid fibroblast. PMID- 25129758 TI - Biosynthesis of oligodextrans with different Mw by synergistic catalysis of dextransucrase and dextranase. AB - In this study, we have investigated various adding times of dextranase to the dextransucrase system to reveal the synergistic process of dextransucrase and dextranase. Dextranase added into the dextransucrase-sucrose system at different times gave rise to different main dextran products. The results showed that dextranase added into sucrose system at the same time with dextransucrase synthesized low molecular weight (Mw) dextran targeted to 5 kDa, while dextranase added during the reaction process of dextransucrase directionally prepared dextran with medium Mw of 10 kDa and 20 kDa. Fourier-transform infrared (FTIR) spectroscopy and (1)H Nuclear magnetic resonance (NMR) exhibited that the synthesized oligodextrans were mainly composed of alpha-1,6-glycosidic linkages (dextran 6587 Da, 96.82%; dextran 22,521 Da, 96.03%) and low alpha-1,3-glycosidic branch. The research established the relationship between the synergistic catalysis of the double enzymatic system and the synthesis of oligodextrans with different Mw. PMID- 25129759 TI - Optimum extraction of polysaccharides from motherwort leaf and its antioxidant and antimicrobial activities. AB - Box-Behnken design was employed to optimize the extraction conditions for polysaccharides from the leaves of motherwort (Leonurus cardiaca L.). Three independent variables including extraction temperature (60-100 degrees C), extraction time (60-120 min), and the ratio of water to raw material (20-60) were investigated. The results revealed that the quadratic and linear terms of three factors had strong effects on the extraction yield of polysaccharides from motherwort leaf. The best extraction conditions for the yield of polysaccharide (LCLP) was extraction temperature of 81.4 degrees C, time of 106.6 min and the ratio of water to raw material of 45.2. Under the optimal conditions, the extraction yield of LCLP was 9.17 +/- 0.39%, which was well matched with value predicted by the model 9.26%. The results indicated that the purified LCLP exerted obvious scavenging effects on free radicals in vitro. Furthermore, motherwort polysaccharides could be used as a novel antimicrobial additive. PMID- 25129760 TI - Purification and structural data of a highly substituted exopolysaccharide from Pseudomonas stutzeri AS22. AB - Pseudomonas stutzeri AS22, when grown on media containing starch and yeast extract and incubated at 30 degrees C and 200 rpm for 24h, was found to produce an acidic and high-molecular mass exopolysaccharide (EPS22). The EPS22 was purified and a yield of 1.3g/l was achieved. The average molecular mass of the EPS22 was determined by high-performance size-exclusion chromatography (HPSEC) and showed an average molecular mass of 9.9 * 10(5)Da and a polydispersity index Mw/Mn (Mw, weight-average and Mn, number-average) of 1.197 +/- 0.015. Structural data of this EPS22 were determined using a combination approach including monosaccharide composition (HPAEC-PAD and GLC), methylation analysis (GC-MS) and NMR spectroscopy analysis. EPS22 was found to be a complex heteropolysaccharide with a repeating unit mainly composed of glucose, mannose and lactyl rhamnose in a molar ratio of 1:1.1:0.7. The acidic nature of the polysaccharide is due to the presence of three non-osidic substituents consisting of a lactyl, acetyl, and pyruvyl groups. PMID- 25129761 TI - Hydroxyl radical-induced crosslinking and radiation-initiated hydrogel formation in dilute aqueous solutions of carboxymethylcellulose. AB - Ionizing radiation causes chain scission of polysaccharides in the absence of crosslinking agents. It has been demonstrated before that degradation of carboxyalkylated polysaccharides may be prevented, despite presence of strong electrostatic repulsing forces between chains, at very high polymer concentration in water (paste-like state) when physical proximity promotes recombination of radiation-generated polymer radicals. In such conditions, crosslinking dominates over chain scission and covalent, macroscopic gels can be formed. In an approach proposed in this work, neutralizing the charges on carboxymethylcellulose (CMC) by lowering the pH results in retracting the electrostatic repulsion between chain segments and thus allows for substantial reduction of polymer concentration required to achieve gelation due to domination of crosslinking reactions. Electron-beam irradiation of aqueous solutions of low pH containing 0.5-2% CMC results in hydrogel formation with 70% yield, while both concentration and dose determine their swelling properties. Time-resolved studies by laser flash photolysis clearly indicate strong pH influence on decay kinetics of CMC radicals. PMID- 25129762 TI - Removing polysaccharides-and saccharides-related coloring impurities in alkyl polyglycosides by bleaching with the H2O2/TAED/NaHCO3 system. AB - The effect of H2O2/TAED/NaHCO3 system, namely NaHCO3 as alkaline agent with the (tetra acetyl ethylene diamine (TAED)) TAED-activated peroxide system, bleaching of alkyl polyglycosides solution was studied by spectrophotometry. The results showed that the optimal bleaching conditions about H2O2/TAED/NaHCO3 system bleaching of alkyl polyglycosides solution were as follows: molar ratio of TAED to H2O2 was 0.06, addition of H2O2 was 8.6%, addition of NaHCO3 was 3.2%, bleaching temperature of 50-65 degrees C, addition of MgO was 0.13%, and bleaching time was 8h. If too much amount of NaHCO3 was added to the system and maintained alkaline pH, the bleaching effect would be greatly reduced. Fixing molar ratio of TAED to H2O2 and increasing the amount of H2O2 were beneficial to improve the whiteness of alkyl polyglycosides, but adding too much amount of H2O2 would reduce the transparency. In the TAED-activated peroxide system, NaHCO3 as alkaline agent and buffer agent, could overcome the disadvantage of producing black precipitates when NaOH as alkaline agent. PMID- 25129763 TI - Correlation of chemical, structural and thermal properties of natural fibres for their sustainable exploitation. AB - The potential of lignocellulosic natural fibres as renewable resources for thermal conversion and material reinforcement is largely dependent on the correlation between their chemical composition, crystalline structure and thermal decomposition properties. Significant differences were observed in the chemical composition of cotton, flax, hemp, kenaf and jute natural fibres in terms of cellulose, hemicellulose and lignin content, which influence their morphology, thermal properties and pyrolysis product distribution. A suitable methodology to study the kinetics of the thermal decomposition process of lignocellulosic fibres is proposed combining different models (Friedman, Flynn-Wall-Ozawa, Criado and Coats-Redfern). Cellulose pyrolysis can be modelled with similar kinetic parameters for all the natural fibres whereas the kinetic parameters for hemicellulose pyrolysis show intrinsic differences that can be assigned to the heterogeneous hemicellulose sugar composition in each natural fibre. This study provides the ground to critically select the most promising fibres to be used either for biofuel or material applications. PMID- 25129764 TI - Rheological properties of micro-/nanofibrillated cellulose suspensions: wall-slip and shear banding phenomena. AB - The rheological properties of enzymatically hydrolyzed and TEMPO-oxidized microfibrillated/nanofibrillated cellulose (MFC/NFC) aqueous suspensions were investigated in oscillation and steady-flow modes and were compared with the morphology of the studied materials. The flow instabilities, which introduce an error in the rheological measurements, were discovered during flow measurements. A wall-slip (interfacial slippage on the edge of geometry tools and suspension) was detected at low shear rates for two types of NFC suspensions while applying cone-plate geometry. A roughening of the tool surfaces was performed to overcome the aforementioned problem. Applying to TEMPO-oxidized NFC, a stronger suspension response was detected at low shear rates with higher values of measured shear stress. However, a shear banding (localization of shear within a sample volume) became more pronounced. The use of serrated tools for enzymatically hydrolyzed NFC produced lower shear stress at the moderate shear rates, which was influenced by water release from the suspension. PMID- 25129765 TI - Molecular self assembly of mixed comb-like dextran surfactant polymers for SPR virus detection. AB - The synthesis of two comb-like dextran surfactant polymers, that are different in their dextran molecular weight (MW) distribution and the presence of carboxylic groups, and their characterization are reported. A bimodal carboxylic dextran surfactant polymer consists of poly(vinyl amine) (PVAm) backbone with carboxyl higher MW dextran, non-functionalized lower MW dextran and hydrophobic hexyl branches; while a monomodal dextran surfactant polymer is PVAm grafted with non functionalized lower MW dextran and hexyl branches. Layer formation of non covalently attached dextran chains with bimodal MW distributions on a surface plasmon resonance (SPR) chip was investigated from the perspective of mixed physisorption of the bimodal and monomodal surfactant polymers. Separation distances between the carboxylic longer dextran side chains within the bimodal surfactant polymer and between the whole bimodal surfactant molecules on the chip surface could be well-controlled. SPR analysis of shrimp yellow head virus using our mixed surfactant chips showed dependence on synergetic adjustment of these separation distances. PMID- 25129766 TI - Chemo-selective high yield microwave assisted reaction turns cellulose to green chemicals. AB - Exceptionally high cellulose liquefaction yields, up to 87% as calculated from the amount of solid residue, were obtained under mild conditions by utilizing the synergistic effect of microwave radiation and acid catalysis. The effect of processing conditions on degradation products was fingerprinted by rapid laser desorption ionization-mass spectrometry (LDI-MS) method. The reaction was chemo tunable, enabling production of glucose (Glc) or levulinic acid (LeA) at significantly high selectivity and yields, the relative molar yields being up to 50 and 69%, respectively. A turning point from pure depolymerization to glucose to further degradation to levulinic acid and formic acid was observed at approximately 50% liquefaction or above 140 degrees C. This was accompanied by the formation of small amounts of solid spherical carbonized residues. The reaction was monitored by multiple analytical techniques. The high yields were connected to the ability of the process to break the strong secondary interactions in cellulose. The developed method has great potential for future production of green platform chemicals. PMID- 25129767 TI - Analysis of isoamylase debranched starches with size exclusion chromatography utilizing PFG columns. AB - Debranched starches were tested with a previously developed method for size exclusion chromatography (SEC) with multi detection utilizing different columns than usually used for the separation of starch in DMSO. A number of debranched starches were analyzed. This system allows good separation of amylose and amylopectin after debranching of starch, and provides quantitative information on the amylose content. Additionally molar mass versus hydrodynamic radii (Rh) distributions of various debranched starches show that the debranching was not 100% and that the differences in the structure of various starches can be followed. PMID- 25129768 TI - Simple synthesis and chelation capacity of N-(2-sulfoethyl)chitosan, a taurine derivative. AB - This study presents a simple and effective synthesis method of N-(2 sulfoethyl)chitosan (NSE-chitosan) via a reaction between sodium 2 bromoethanesulfonate and chitosan that allows polymer transformation without using additional reagents and organic solvents. The chemical structure of the obtained NSE-chitosan was characterized by FT-IR and (1)H NMR spectroscopies. Thermogravimetric study of NSE-chitosan coupled with FT-IR analysis has shown stability of the polymer up to 200 degrees C, which almost does not change with the increase of degree of substitution (DS). The sorption of transition and alkaline earth metal ions from multicomponent solutions on NSE-chitosan was investigated. The synthesized sorbents showed the selective recovery of silver(I) and copper(II) ions from ammonium acetate buffer solution. The increase of DS enhanced the selectivity to silver(I) ions sorption in comparison with copper(II) ions. Selectivity coefficients K(Ag/Cu) increase from 1.3 to 10.9 with DS increasing up to 0.7 (ammonium acetate buffer solution, pH 6.5). Sorption isotherms of transition metal ions on NSE-chitosan with DS = 0.5 have been fitted using Langmuir, Freundlich, and Redlich-Peterson models. The maximum sorption capacities of sorbent in ammonium acetate buffer solution at pH 6.0 were 1.72 mmol/g for Cu(II), 1.23 mmol/g for Ag(I) and below 0.5 mmol/g for Co(II), Zn(II), Cd(II), Pb(II), Mn(II) and Ni(II) ions. PMID- 25129769 TI - An antioxidative galactomannan-protein complex isolated from fermentation broth of a medicinal fungus Cs-HK1. AB - A protein-containing polysaccharide, EPS2BW, was fractionated from the exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis (Cs HK1). EPS2BW was mainly composed of galactomannan with about 16% (w/w) protein and 50 kDa average molecular weight. The galactomannan part consisted of mannose and galactose at 1.7:1.0 molar ratio, and the protein segments were composed of sixteen amino acids with 12.5% proline and 16.6% threonine (mol%) being the most abundant. Based on analytical results from NMR, methylation analysis, partial acid hydrolysis and GC-MS, the galactomannan structure was elucidated as a (1 -> 2)-alpha-D-mannopyranosyl (Manp) backbone with O-6-linked galactopyranosyl (Galp) branches. EPS2BW exhibited a high antioxidant capacity in both chemical and cell culture assays, with a Trolox equivalent radical scavenging activity of 44.7 MUmol Trolox/mg, a Fe(3+) reducing power of 38.9 MUmol Fe(2+)/mg, and significant cytoprotective effect against H2O2-induced PC12 cell death at 50-250 MUg/mL. PMID- 25129770 TI - Characterization of glucomannan from Amorphophallus oncophyllus and its prebiotic activity in vivo. AB - Porang (Amorphophallus oncophyllus) is local perennial plant rich in glucomannan. The aim of this study was to extract and characterize glucomannan from porang tuber and to evaluate its potency as prebiotic in vivo. The research consisted of the following steps, i.e. extraction of glucomannan, evaluation of its physico chemical properties, and in vivo study. Extraction was done by immersing porang fluor with water at 55 degrees C followed by coagulating glucomannan using ethanol. Solubility, water holding capacity, viscosity, degree of acetylation, degree of polymerization (DP), and purity of the glucomannan were evaluated. In vivo study was done using thirty-two Wistar rats which were divided into four groups. Each group was treated for 14 days with standard AIN 93 (standard), porang glucomannan, commercial konjac glucomannan, and inulin diet as source of fiber. Bacterial population and chemical properties of digesta were analyzed after intervention. The results of the study indicated that the yield of glucomannan from porang flour was 18.05% with 92.69% purity. Compared to commercial glucomannan, porang glucomannan showed higher solubility (86.4%) and degree of acetylation (13.7%), but lower viscosity (5400 cps), WHC (34.5 g/g), and DP (9.4). Diet supplemented with porang glucomannan inhibited the growth of Escherichia coli, enhanced the production of total SCFA, and reduced pH value of cecal content. The study indicated that glucomannan from porang may be used as functional food. PMID- 25129771 TI - Effect of hyaluronic acid on the thermogelation and biocompatibility of its blends with methyl cellulose. AB - Aim of this work was to investigate the influence of hyaluronic acid (HA) molecular weight on the thermogelation and biocompatibility of its blends with methyl cellulose in view of a possible application in drug delivery and/or wound healing. We found out that it was possible to obtain MC/HA blends showing a rheological behavior typical of a viscous solution at 20 degrees C and of a weak gel at 37 degrees C only when blending MC with low molecular weight HA. Moreover, the blends containing low molecular weight HA did not affect human foreskin fetal fibroblasts viability, proliferation and migration. On the contrary, the cell incubation with high molecular weight HA resulted in a marked and significant reduction of cell viability, compared to control cells. Finally, the optimized blends, in terms of rheological properties and biocompatibility, proved to be able to control and prolong bovine serum albumin release by a combined mechanism of platform dissolution and drug diffusion. PMID- 25129772 TI - The role of poly-M and poly-GM sequences in the metal-mediated assembly of alginate gels. AB - Whilst the involvement of poly-G sequences in the formation of metal-mediated alginate gels has been previously studied in some detail, investigations into the role of poly-M and poly-GM sequences has been relatively neglected. In this regard, the binding of sodium and calcium ions to poly-M and poly-GM decamers, and their influence on chain aggregation, has been modelled by conducting a series of molecular dynamics simulations. This work complements a previous analogous study carried out for the poly-G decamer, whereby up to three strands are systematically introduced into each simulation. As in the previous study, this method allows intrinsic binding modes and interchain structural motifs to be revealed, that are consistent with those observed in available AFM images of consolidated 3-D networks. It is apparent from these studies that different sequences have different structural implications for metal-mediated chain association. PMID- 25129773 TI - Gas permeability and selectivity of cellulose nanocrystals films (layers) deposited by spin coating. AB - Cellulose nanocrystals (CNC) were extracted from a cellulose residue using two different acid hydrolysis procedures. CNC extracted with sulfuric acid (CNC(S)) showed higher surface charge (339 MUmol/g) compared with crystals extracted with hydrochloric acid (CNC(HCl)). Spin-coated films with two different configurations were prepared; the first with alternate layers of poly(allylamine hydrochloride) (PAHCl) and CNC, and the second with a single layer of PAHCl coated with multilayers of CNC. Film characteristics such as roughness, thickness, contact angle, orientation, gas permeability and gas selectivity were studied. Optical microscopy showed more homogeneous films of CNC(S) compared to CNC(HCl). The surface charge of the crystals impacted the films' hydrophobicity, being highest for 25 alternate layers of PAHCl and CNC(HCl). The gas permeability coefficient was different for each film, depending primarily on the surface charge of the crystals and secondly on the film configuration. The films made with CNC(HCl) displayed gas barriers with nitrogen and oxygen, and gas selectivity with some gas combinations. CNC(S) films did not show gas selectivity. These results indicate that CNC with low surface charge can be further developed for gas separation and barrier applications. PMID- 25129775 TI - Hydroxypropyl cellulose stabilizes amorphous solid dispersions of the poorly water soluble drug felodipine. AB - Overcoming the low oral bioavailability of many drugs due to their poor aqueous solubility is one of the major challenges in the pharmaceutical industry. The production of amorphous solid dispersions (ASDs) of these drugs using hydrophilic polymers may significantly improve their solubility. However, their storage stability and the stability of their supersaturated solutions in the gastrointestinal tract upon administration are unsolved problems. We have investigated the potential of a low viscosity grade of a cellulosic polymer, hydroxypropyl cellulose (HPC-SSL), and compared it with a commonly used vinyl polymer, polyvinylpyrrolidone vinyl acetate (PVP-VA), for stabilizing the ASDs of a poorly water soluble drug, felodipine. The ASDs were produced using hot melt mixing and stored under standard and accelerated stability conditions. The ASDs were characterized using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. Drug dissolution and partitioning rates were evaluated using single- and biphasic dissolution studies. The ASDs displayed superior drug dissolution and partitioning as compared to the pure crystalline drug, which might be attributed to the formation of a drug polymer molecular dispersion, amorphous conversion of the drug, and drug-polymer hydrogen bonding interactions. Late phase separation and early re-crystallization occurred at lower and higher storage temperatures, respectively, for HPC-SSL ASDs, whereas early phase separation, even at low storage temperatures, was noted for PVP-VA ASDs. Consequently, the partitioning rates for ASDs dispersed in HPC SSL were greater than those of PVP-VA at lower and room temperature storage, whereas the performance of both of the ASDs was similar when stored at higher temperatures. PMID- 25129774 TI - Preparation and characterization of galactosylated alginate-chitosan oligomer microcapsule for hepatocytes microencapsulation. AB - Galactosylated alginate (GA)-chitosan oligomer microcapsule was prepared to provide a sufficient mechanical stability, a selective permeability and an appropriate three-dimensional (3D) microenvironment for hepatocytes microencapsulation. The microcapsule has a unique asymmetric membrane structure, with a dense layer located in the inner surface and gradually decreasing toward the outside surface. The stable microcapsule was obtained when GA lower than 50%, while the permeability was increased with increasing of GA. A balance between mechanical stability and permeability was achieved through modulating membrane porosity and thickness. The optimal microcapsule displays a selective permeability allowing efficient transport of human serum albumin while effectively blocking immunoglobulin G. Hepatocytes exhibited high and long term viability (>92%), proliferability, multicellular spheroid morphology, and enhancement of liver-specific functions in the microcapsule wherein galactose moieties present chemical cues to support cell-matrix interactions while the 3D structure of the microcapsule behaves physical cues to facilitate cell-cell interactions. PMID- 25129776 TI - Polyoxometalates acid treatment for preparing starch nanoparticles. AB - In this article, a new way of preparing starch-based nanoparticles (SNPs) with high yields by a polyoxometalates acid treatment is presented. The particle morphology, mean size and size distribution of the obtained SNPs are characterized using a dynamic light scattering (DLS) and scanning electron microscope (SEM). By changing parameters such as temperature, concentration of polyoxometalates and treating time the size of SNPs can be controlled. In addition, there are no changes in the structures of the starch granules as confirmed by IR or (1)H NMR. Freeze-dried SNPs are amorphous as characterized by wide-angle X-ray diffraction (WXRD). PMID- 25129777 TI - Influence of both cation and alginate nature on the rheological behavior of transition metal alginate gels. AB - The rheological properties of several ionotropic alginate hydrogels were investigated according to the nature of the divalent cation (Mn(2+), Co(2+), Cu(2+)) and the guluronic fraction of the alginate (HG and LG for "high G content" and "low G-content"). Six hydrogels (Mn-LG, Mn-HG, Co-LG, Co-HG, Cu-LG and Cu-HG) were synthesized and studied by spectromechanical analyses. On one hand, Cu-HG, Cu-LG and Co-HG behaved as viscoelastic solids: the elastic contribution was higher than the dissipative component in all the frequency range studied (G'>G"). No flow zone (G">G') was detected even at very low values of the shearing frequency. On the other, Mn-HG, Mn-LG and Co-LG presented a spectromechanical behavior that resembled that observed classically for entangled polymers. Indeed, at high frequency, these latter materials could be compared to a viscoelastic solid but at low frequency, the flow zone was described and the viscous character became prevalent with finite relaxation time. Very good correlations with the microscopic structurations of the network were evidenced (rubbery vs. flow zone and fibrillar vs. complex morphology respectively). PMID- 25129778 TI - Novel polymer Li-ion binder carboxymethyl cellulose derivative enhanced electrochemical performance for Li-ion batteries. AB - Novel water-based binder lithium carboxymethyl cellulose (CMC-Li) is synthesized by cotton as raw material. The mechanism of the CMC-Li as a binder is reported. Electrochemical properties of batteries' cathodes based on commercially available lithium iron phosphate (LiFePO4, LFP) and water-soluble binder are investigated. Sodium carboxymethyl cellulose (CMC-Na, CMC) and CMC-Li are used as the binder. After 200 cycles, compared with conventional poly(vinylidene fluoride) (PVDF) binder, the CMC-Li binder significantly improves cycling performance of the LFP cathode 96.7% of initial reversible capacity achieved at 175 mA h g(-1). Constant current charge-discharge test results demonstrate that the LFP electrode using CMC-Li as the binder has the highest rate capability, followed closely by those using CMC and PVDF binders, respectively. Electrochemical impedance spectroscopy test results show that the electrode using CMC-Li as the binder has lower charge transfer resistance than the electrodes using CMC and PVDF as the binders. PMID- 25129779 TI - Green synthesis of silver and gold nanoparticles employing levan, a biopolymer from Acetobacter xylinum NCIM 2526, as a reducing agent and capping agent. AB - With a vision of finding greener materials to synthesize nanoparticles, we report the production and isolation of levan, a polysaccharide with repeating units of fructose, from Acetobacter xylinum NCIM2526. The isolated levan were characterized using potassium ferricyanide reducing power assay, Fourier transform infra-red (FTIR) spectroscopy and (1)H nuclear magnetic resonance spectroscopy ((1)H NMR). To exploit levan in nanotechnology, we present a simple and greener method to synthesize silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) using biopolymer, levan as both reducing and stabilizing agents. The morphology and stability of the AgNPs and AuNPs were examined by transmission electron microscopy (TEM) and UV-vis absorption (UV-vis) spectroscopy. The possible capping mechanism of the nanoparticles was postulated using FTIR studies. As synthesized biogenic nanoparticles showed excellent catalytic activity as evidenced from sodium borohydride mediated reduction of 4 nitro phenol and methylene blue. PMID- 25129780 TI - Inter vs. intraglycosidic acetal linkages control sulfation pattern in semi synthetic chondroitin sulfate. AB - Microbial-sourced unsulfated chondroitin could be converted into chondroitin sulfate (CS) polysaccharide by a multi-step strategy relying upon benzylidenation and acetylation reactions as key-steps for its regioselective protection. By conducting the two reactions one- or two-pots, CSs with different sulfation patterns could be obtained at the end of the semi-synthesis. In particular, a CS polysaccharide possessing sulfate groups randomly distributed between positions 4 and 6 of N-acetyl-galactosamine (GalNAc) units could be obtained through the two pots route, whereas the one-pot pathway allowed an additional sulfation at position 3 of some glucuronic acid (GlcA) units. This difference was ascribed to the stabilization of a labile interglycosidic benzylidene acetal involving positions O-3 and O-6 of some GlcA and GalNAc, respectively, when the benzylidene acetylation reactions were conducted in a one-pot fashion. Isolation and characterization of a polysaccharide intermediate showing interglycosidic acetal moieties was accomplished. PMID- 25129781 TI - Dextran synthesized by Leuconostoc mesenteroides BD1710 in tomato juice supplemented with sucrose. AB - The characteristics of the growth of Leuconostoc mesenteroides BD1710 and the synthesis of dextran in tomato juice supplemented with 15% sucrose were assayed. L. mesenteroides BD1710 could synthesize approximately 32 g L(-1) dextran in the tomato-juice-sucrose medium when cultured at 28 degrees C for 48 h, which was on the same level as the dextran yield in a chemically defined medium. The viscosity of the cultured tomato-juice-sucrose medium with various dextran contents was also measured. The results of the monosaccharide composition, molecular-weight distribution, Fourier transform infrared spectra (FTIR) and nuclear magnetic resonance spectra (NMR) showed that the polysaccharide synthesized by L. mesenteroides BD1710 in the tomato-juice-sucrose medium was dextran with a peak molecular weight of 6.35 * 10(5)Da, a linear backbone composed of consecutive alpha-(1 -> 6)-linked d-glucopyranosyl units and approximately 6% alpha-(1 -> 3) branches. PMID- 25129782 TI - In vitro fermentation of the polysaccharides from Cyclocarya paliurus leaves by human fecal inoculums. AB - In vitro fermentation of polysaccharide from Cyclocarya paliurus leaves by human fecal inoculums was investigated by determining the changes in contents of neutral and reducing sugar and pH value, consumption of monosaccharide and production of short-chain fatty acids (SCFAs). During fermentation, the content of neutral sugar and reducing sugar decreased as fermentation time increased except that the content of reducing sugar increased within the fermentation time 0.5h. The pH value significantly dropped from 7.2 to 6.04. Remarkably, the greatest yields and the fastest consumption of galacturonic acid were found and the yield of glucose and arabinose were relatively high. The dominant SCFAs, which were acetic acid, propionic acid and n-butyric acid, significantly increased. These results showed that polysaccharide was partly fermented, glycosidic bonds with galacturonic acid being more susceptible to be attacked by gut bacteria and galacturonic acid might be deemed as the main producer of acetic acid. PMID- 25129783 TI - Hydration and the phase diagram of acid hydrolyzed potato starch. AB - We investigated hydration of acid hydrolyzed potato starch (maltodextrin) employing a multi-method approach. In particular, synchrotron radiation X-ray scattering and differential scanning calorimetry were used, and, for the first time, the material was investigated with sorption calorimetry and a newly developed quartz crystal microbalance with humidity scanning. The dry starch was found to be in an amorphous state. During hydration it exhibits a glass transition in both bulk and thin film samples, followed by an exothermic event where the starch crystallized. Recrystallized bulk samples displayed neither a pronounced glass transition nor crystallization upon hydration whereas both events occurred in thin film samples. The hydration-driven crystallization resulted in an X-ray pattern consistent with the coexistence of A and B type crystallites; however, at higher water concentrations only the B form occurred. The results were used to construct the first ever acid hydrolyzed starch-water phase diagram. PMID- 25129785 TI - Preparation of oxidized agar and characterization of its properties. AB - A series of oxidized agars with different carboxyl content were prepared, and their properties were determined and analyzed. The results showed that the gelling temperature, the optical rotation and the apparent viscosity of the agar solution, and the melting temperature, the strength, the hardness, the fracturability, the springiness, the chewiness and the gumminess of agar gel all decreased except that the cohesiveness increased after oxidation. The gel skeleton structures of agar before and after oxidation were all of the porous network structures, but the pores of gel skeleton structure became smaller and denser after oxidation. PMID- 25129784 TI - Free-radical degradation by Fe2+/Vc/H2O2 and antioxidant activity of polysaccharide from Tremella fuciformis. AB - The free-radical degradation and antioxidant activity of polysaccharide from Tremella fuciformis was investigated. In present study, the combination of Fe(2+), ascorbic acid and H2O2 was used as degradation regents in order to obtain the lower molecular weight product. The result ascertained oxidative-reduce degradation did not change the main structure of polysaccharides in the test conditions. Five degraded polysaccharides were selected to evaluate their antioxidant activities in vitro. It was found that the degraded sample with lower molecular weight possessed the higher antioxidant activities. It was possible that free-radical degradation is an effective way for enhancing antioxidant activity to decrease molecular weight of polysaccharides. PMID- 25129786 TI - Probing the structural details of xylan degradation by real-time NMR spectroscopy. AB - The biodegradation of abundantly available cell wall polysaccharides has recently received much attention, not least because cell wall polysaccharides are substrates for the human gut microbiota and for environmentally sustainable processes of biomass conversion to value-added compounds. A major fraction of cereal cell wall polysaccharides consists of arabinoxylans. Arabinoxylan and its degradation products are therefore present in a variety of agro-industrial residues and products. Here, we undertook to track the structural details of wheat arabinoxylan degradation with high resolution NMR spectroscopy. More than 15 carbohydrate residues were distinguished in the substrate and more than 20 residues in partially degraded samples without any sample cleanup. The resolution of a plethora of structural motifs in situ permits the readout of persisting structures in degradation processes and in products. Reaction progress was visualized for the biodegradation of arabinoxylan by different crude microbial enzyme preparations. The direct observation of structural details in complex mixtures containing arabinoxylan fragments is significant, as such structural details reportedly modulate the health-promoting functions of arabinoxylan fragments. PMID- 25129787 TI - Hydroxyethylcellulose used as an eco-friendly inhibitor for 1018 c-steel corrosion in 3.5% NaCl solution. AB - The inhibition effect of hydroxyethylcellulose (HEC) on 1018 c-steel corrosion in 3.5% NaCl solution was investigated by using potentiodynamic polarization, electrochemical frequency modulation (EFM) and electrochemical impedance spectroscopy (EIS) techniques. The potentiodynamic polarization studies suggested that HEC acts as a mixed-type inhibitor. Data obtained from EIS were analyzed to model the corrosion inhibition process through equivalent circuit. Results obtained from EFM technique were shown to be in agreement with potentiodynamic and EIS techniques. The adsorption behavior of HEC on steel surface follows the Langmuir adsorption isotherm. Thermodynamic parameter (DeltaG degrees (ads)) and activation parameters (Ea(*), DeltaH(*) and DeltaS(*)) were calculated to investigate mechanism of inhibition. Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analysis system were performed to characterize the film formed on the metal surface. DMol(3) quantum chemical calculations were performed to support the adsorption mechanism with the structure of HEC molecule. PMID- 25129788 TI - Effect of carboxymethylation on antioxidant properties and radical degradation of mannans and glucans. AB - Carboxymethyl derivatives (CM-derivatives) of alpha,beta-mannans from yeasts, Saccharomyces cerevisiae beta-glucan and dextran (alpha-glucan) were found to possess strong antioxidant activities against reactive hydroxyl radicals (OH*) compared to underivatized polysaccharides. When CM-derivatives having similar DS (0.41-0.45) were compared, the antioxidant activity decreased in order CM mannan>CM-beta-glucan>CM-dextran. Moreover, the antioxidant activities against OH* increased with increasing degree of substitution (DS) of polysaccharides. The CM-mannan and CM-dextran with the highest DS (0.73 and 1.1, respectively) were the strongest antioxidants and their degradation by OH* decreased with increased carboxymethylation. The scavenging abilities of CM-polysaccharides against stable DPPH radical (DPPH) were lower than those of original underivatized ones. Also this scavenging property against DPPH was lower compared to antioxidant effect against OH*. PMID- 25129789 TI - Purification, characterisation and protective effects of polysaccharides from alfalfa on hepatocytes. AB - The objective of this study was to determine the preliminary characteristics and protective effects of alfalfa polysaccharides (APS) on hepatocytes in vitro. The crude APS was purified by DEAE-cellulose and Sephadex G-100 chromatography, resulting in the four purified fractions: APS-1, APS-2, APS-3 and APS-4. The results indicated that APS-3 had higher carbohydrate and uronic acid contents and that APS-4 had a more complicated monosaccharide composition compared to the other purified fractions. The average molecular weights of APS-1, APS-2, APS-3 and APS-4 were 48,536, 6,221, 66,559 and 13,076 Da, respectively. Furthermore, APS (crude and its purified fractions) restored the activities of antioxidant enzymes and increased the total antioxidant capacity of hepatocytes subjected to H2O2-induced oxidative stress. Furthermore, APS treatment counteracted the increases in lactic dehydrogenase and malonaldehyde in the culture supernatant. These results clearly demonstrate that APS possesses a protective effect against oxidative injury in hepatocytes. PMID- 25129790 TI - Effects of carbohydrate sources on biosorption properties of the novel exopolysaccharides produced by Arthrobacter ps-5. AB - The crude exopolysaccharides (EPSs) were obtained from Arthrobacter ps-5 fermentation using various carbohydrate sources followed by centrifugation, ethanol precipitation, and the isolated EPSs were further deproteinized and lyophilized. Carbohydrates from various sources resulted in different yield of EPSs from the fermentation and different molecular weight of EPSs. A maximum yield of 0.27 mg/g was achieved by using the culture medium supplemented with sucrose. The EPS produced by glucose-supplemented medium had the maximum content of acidic polysaccharides, subsequently presented the highest biosorption capacity for Cu(2+) and Pb(2+) at 257.9 mg/g and 331.8 mg/g, respectively. The ratio of acidic to neutral polysaccharides presented in EPSs was a key factor to explicate the biosorption mechanism, the higher the ratio, the stronger the biosorption capacity. PMID- 25129791 TI - Process optimization and analysis of microwave assisted extraction of pectin from dragon fruit peel. AB - Microwave assisted extraction (MAE) technique was employed for the extraction of pectin from dragon fruit peel. The extracting parameters were optimized by using four-variable-three-level Box-Behnken design (BBD) coupled with response surface methodology (RSM). RSM analysis indicated good correspondence between experimental and predicted values. 3D response surface plots were used to study the interactive effects of process variables on extraction of pectin. The optimum extraction conditions for the maximum yield of pectin were power of 400 W, temperature of 45 degrees C, extracting time of 20 min and solid-liquid ratio of 24 g/mL. Under these conditions, 7.5% of pectin was extracted. PMID- 25129792 TI - pH sensitive N-succinyl chitosan grafted polyacrylamide hydrogel for oral insulin delivery. AB - pH sensitive PAA/S-chitosan hydrogel was prepared using ammonium persulfate (APS) as an initiator and methylenebisacrylamide (MBA) as a crosslinker for oral insulin delivery. The synthesized copolymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) study; morphology was observed under scanning electron microscope (SEM). The PAA/S chitosan with ~ 38% of insulin loading efficiency (LE) and ~ 76% of insulin encapsulation efficiency (EE), showed excellent pH sensitivity, retaining ~ 26% of encapsulated insulin in acidic stomach pH 1.2 and releasing of ~ 98% of insulin in the intestine (pH 7.4), providing a prolonged attachment with the intestinal tissue. The oral administration of insulin loaded PAA/S-chitosan hydrogel was successful in lowering the blood glucose level of diabetic mice. The bioavailability of insulin was ~ 4.43%. Furthermore, no lethality or toxicity was documented after its peroral administration. Thus, PAA/S-chitosan hydrogel could serve as a promising oral insulin carrier in future. PMID- 25129793 TI - Molecular engineering of manipulated alginate-based polyurethanes. AB - The novel soluble alginate-based polyurethanes in organic solvents were synthesized by the reaction of NCO-terminated prepolymers and tributylammonium alginate (TBA-Alg) for the first time. The chemical structures of synthesized polyurethanes were characterized using FTIR, (1)H NMR and TGA. The reaction completion was confirmed by disappearing of NCO band in FTIR spectra. Furthermore, a peak at 4.71 ppm and some small peaks at a range of 4.12-4.37 ppm in the (1)H NMR of alginate-based polyurethanes were assigned to the backbone of alginate. The results of both FTIR and (1)H NMR were remarkably confirmed by TGA data. The ionic nature of polyurethane backbone not only affects on thermal properties of samples, but it also changes the chemically-bonded alginate morphology. Both polyether and polyester based non-ionic polyurethanes extended by TBA-Alg illustrated the distinct alginate, whereas those ionomers extended by alginate were appeared as the continuous systems at nanoscale. PMID- 25129794 TI - Enzymatic hydrolysis studies of arabinogalactan-protein structure from Acacia gum: the self-similarity hypothesis of assembly from a common building block. AB - Arabinogalactan (AG) and arabinogalactan-protein (AGP) fractions were treated enzymatically using several proteases in acidic (pH 4) and alkaline (pH 7) conditions in order to go deeper insight into the structure and conformations of the two main fractions of Acacia senegal gum. Endoproteinase Glu-C, pepsin and phosphatase acid were thus used in acidic conditions while subtilisin A, pronase, trypsin, papain and proteinase K were used in alkaline conditions to cleave protein moieties of the two fractions. Structures of AG and AGP were probed using HPSEC-MALLS, small angle neutron scattering and far-UV circular dichroism. Enzymes did not affect AG fraction structure whatever the pH conditions used, highlighting the inaccessibility of the peptide backbone and the remarkable stability of this fraction in acidic and alkaline conditions. This result was in agreement with the thin oblate ellipsoid model we previously identified for the AG fraction where the 43 amino-acid residues peptide sequence was supposed, based on spectroscopic methods, to be totally buried. Contrary to AG fraction, AGP protein component was therefore cleaved using enzymes in alkaline conditions, the absence of enzymatic efficiency in acidic conditions being probably ascribed to long range electrostatic repulsions occurring between negatively charged AGP and enzymes at pH 4. The decrease of AGP molecular weight after hydrolysis in alkaline conditions went from 1.79 * 10(6) g mol(-1) for control AGP to as low as 1.68 * 10(5) g mol(-1) for papain-treated AGP. The overall structure of the enzyme-treated AGPs was found to be surprisingly quite similar whatever the enzyme used and close, with however some subtle differences, to AG unit. A tri axial ellipsoid conformation was found in enzyme-treated AGPs and the two main preferential distances identified in the pair distance distribution function would claim in favor of rod-like or elongated particles or alternatively would indicate the presence of two particles differing in dimensions. The secondary structures content of control and enzyme-treated AGPs were similar, highlighting both the high rigidity of the protein backbone and the overall symmetry of AGP. This conclusion was reinforced by the more compact structures found when AGP was intact compare to the more elongated structures found when AGP was enzymatically cleaved. Finally, the structural similarities found in enzyme-treated AGP together with the theoretical calculations to analytically probe the type of branching would suggest that AGP would be made of a self-similar assembly of two types of building blocks, the second being a five-fold repetition of the first one, for which palindromic amino acid sequence would ensure a self-ordering of carbohydrate moieties along the polypeptide chains. The cleavage would therefore lead to hydrolysed building blocks with similar secondary structures and conformations whatever the enzyme used. PMID- 25129795 TI - Synthesis of alginate bioencapsulated nano-hydroxyapatite composite for selective fluoride sorption. AB - This article focuses on the development of eco-friendly adsorbent by alginate (Alg) bioencapsulating nano-hydroxyapatite (n-HAp) namely n-HApAlg composite for defluoridation studies in batch mode. n-HAp powder utilized as a promising defluoridating material, but it causes a significant pressure drop during field applications. To overcome such technological bottlenecks, n-HApAlg composite was synthesized. The defluoridation capacity (DC) of synthesized n-HApAlg composite possesses an enhanced DC of 3870 mg F(-)/kg when compared to n-HAp and calcium alginate (CaAlg) composite which possess DC of 1296 and 680 mg F(-)/kg, respectively. The biocomposite features were characterized using FTIR and SEM with EDAX analysis. The various adsorption influencing parameters like contact time, pH, co-anions, initial fluoride concentration and temperature were optimized. The adsorption process was enlightened by various isotherms and kinetic models. The suitability of the biocomposite at field conditions was also tested. PMID- 25129796 TI - Nanoporous membranes with cellulose nanocrystals as functional entity in chitosan: removal of dyes from water. AB - Fully biobased composite membranes for water purification were fabricated with cellulose nanocrystals (CNCs) as functional entities in chitosan matrix via freeze-drying process followed by compacting. The chitosan (10 wt%) bound the CNCs in a stable and nanoporous membrane structure with thickness of 250-270 MUm, which was further stabilized by cross-linking with gluteraldehyde vapors. Scanning electron microscopy (SEM) studies revealed well-individualized CNCs embedded in a matrix of chitosan. Brunauer, Emmett and Teller (BET) measurements showed that the membranes were nanoporous with pores in the range of 13-10nm. In spite of the low water flux (64 Lm(-2) h(-1)), the membranes successfully removed 98%, 84% and 70% respectively of positively charged dyes like Victoria Blue 2B, Methyl Violet 2B and Rhodamine 6G, after a contact time of 24h. The removal of dyes was expected to be driven by the electrostatic attraction between negatively charged CNCs and the positively charged dyes. PMID- 25129797 TI - Horse chestnut (Aesculus hippocastanum L.) starch: Basic physico-chemical characteristics and use as thermoplastic material. AB - Starch isolated from non-edible Aesculus hippocastanum seeds was characterized and used for preparing starch-based materials. The apparent amylose content of the isolated starch was 33.1%. The size of starch granules ranged from 0.7 to 35 MUm, and correlated with the shape of granules (spherical, oval and irregular). The chain length distribution profile of amylopectin showed two peaks, at polymerization degree (DP) of 12 and 41-43. Around 53% of branch unit chains had DP in the range of 11-20. A. hippocastanum starch displayed a typical C-type pattern and the maximum decomposition temperature was 317 degrees C. Thermoplastic starch (TPS) prepared from A. hippocastanum with glycerol and processed by melt blending exhibited adequate mechanical and thermal properties. In contrast, plasticized TPS with glycerol:malic acid (1:1) showed lower thermal stability and a pasty and sticky behavior, indicating that malic acid accelerates degradation of starch during processing. PMID- 25129798 TI - Salt stress alters the cell wall polysaccharides and anatomy of coffee (Coffea arabica L.) leaf cells. AB - Coffea arabica is the most important agricultural commodity in the world, and salinity is a major threat to its sustainable irrigation. Coffee leaf polysaccharides from plants subjected to salt stress were extracted and the leaves visualized through optical and electron microscopy. Alterations were detected in the monosaccharide composition of the pectin and hemicelluloses, with increases in uronic acid in all fractions. Changes in the polysaccharides were confirmed by HPSEC and FTIR. Moreover, the monolignol content was increased in the final residue, which suggests increased lignin content. The cytoplasm was altered, and the chloroplasts appeared irregular in shape. The arrangement of the stroma lamellae was disordered, and no starch granules were present. It was concluded that leaves of C. arabica under salt stress showed alterations in cell wall polysaccharides, increased monolignol content and structural damage to the cells of the mesophyll. PMID- 25129799 TI - Preparation and stabilization of D-limonene Pickering emulsions by cellulose nanocrystals. AB - The aim of this study was to investigate D-limonene Pickering emulsion stabilized by cellulose nanocrystals (CNCs) and factors that may affect its properties. CNCs were prepared by ammonium persulfate hydrolysis of corncob cellulose, and D limonene Pickering emulsions were generated by ultrasonic homogenizing method. The morphology and size of the prepared emulsions with different CNCs concentrations were studied by optical microscopy and laser light diffraction. In addition, factors that may affect the stability of emulsions such as ionic concentration, pH and temperature were also studied. As indicated by the experiment data, when temperature rose, the stability to of emulsions would be increased, and the stability of emulsions was reduced with low pH or high salt concentration due to electrostatic screening of the negatively charged CNC particles. In conclusion, high stability of D-limonene Pickering emulsions could be obtained by CNCs. PMID- 25129800 TI - Isolation, structural characterization, and potential applications of hemicelluloses from bamboo: a review. AB - Bamboo is one of the mostly fast growing natural resources and has great potential to be used as a valuable feedstock for biorefinery. The hemicelluloses, next to cellulose, represent a diverse group of polysaccharides in plant cell wall. Elucidation and understanding of the hemicelluloses from bamboo play an important role in the efficient conversion of bamboo into biofuels and bioproducts. This review summarized the recent reports on hemicelluloses from bamboo, including immunohistochemical localization, focused on extraction and purification methods, chemical components, characterization of structural features, as well as physicochemical properties. In addition, attention was also paid to derivatives prepared from bamboo hemicelluloses and to potential applications of bamboo hemicelluloses in a variety of areas such as biomaterials, biofuel, and food. PMID- 25129801 TI - Thermal degradation and stability of cationic starches and their complexes with iodine. AB - Thermal degradation processes of cationic starch (CS) and CS-iodine complex were investigated by thermogravimetry (TG) in air and under nitrogen atmosphere at 10 degrees C min(-1) heating rate and compared. Moreover, the thermal stability of CS with different degree of substitution (DS) and their complexes with iodine was studied by TG under nitrogen atmosphere at different heating rates. The average E(a) values for CS were found to be slightly lower as compared to native starch, suggesting lower thermal stability of modified starches due to cationisation. The main thermodegradation event of native starch-iodine and CS-iodine complexes can be separated in two steps: the release of iodine in the range of 137-196 degrees C, followed by the subsequent iodine induced thermochemical degradation of polysaccharide macromolecules, which appears at lower temperatures than in the absence of iodine. "Blue" inclusion complex showed higher thermal stability than ionic CS-iodine complex. PMID- 25129802 TI - Impact of molecular and crystalline structures on in vitro digestibility of waxy rice starches. AB - The in vitro digestibility, molecular structure and crystalline structure of waxy rice starches isolated from six Korean cultivars (Shinsun, Dongjin, Baekok, Whasun, Chungbaek, and Bosuk) were investigated. The molecular weight (M(w)) of waxy rice starches ranged from 1.1 * 10(8)g/mol to 2.2 * 10(8)g/mol. Chungbaek waxy rice starch had the highest average chain length (24.3) and proportion (20.7%) of long branch chains (DP >= 37), and the lowest proportion (19.0%) of short branch chains (DP 6-12) among the tested six waxy rice starches. The relative crystallinity and intensity ratio of 1047/1022 ranged from 38.9% to 41.1% and from 0.691 to 0.707, respectively. Chungbaek had the highest gelatinization temperature and enthalpy. Chungbaek had the highest pasting temperature (70.7 degrees C), setback (324 cP) and final viscosity (943 cP), whereas Baekok showed the highest peak viscosity (1576 cP) and breakdown (1031 cP). Chungbaek had lower rapidly digestible starch (RDS) content and expected glycemic index (eGI), and higher resistant starch (RS) content, whereas Whasun exhibited higher RDS content and eGI. The slowly digestible starch (SDS) content of Shinsun (38.3%) and Bokok (32.0%) was significantly higher than that of other cultivars (11.3-22.0%). PMID- 25129803 TI - Synthesis of chitosan-PEO hydrogels via mesylation and regioselective Cu(I) catalyzed cycloaddition. AB - In this work, a well-defined hydrogel was developed by coupling chitosan with PEO through "click chemistry". Azide functionalities were introduced onto chitosan, through mesylation of C-6 hydroxyl groups, and reacted with a di-alkyne PEO by a regioselective Cu(I)-catalyzed cycloaddition. This synthetic approach allowed us to obtain a hydrogel with a controlled crosslinking degree. In fact, the extent of coupling is strictly dependent on the amount of azido groups on chitosan, which in turn can be easily modulated. The obtained hydrogel, with a crosslinking degree of around 90%, showed interesting swelling properties. With respect to chitosan hydrogels reported in literature, a considerably higher equilibrium uptake was reached (940%). The possibility to control the crosslinking degree of hydrogel and its capability to rapidly absorb high amounts of water make this material suitable for several applications, such as controlled drug release and wound healing. PMID- 25129804 TI - Redox-stimuli responsive micelles from DOX-encapsulating polycaprolactone-g chitosan oligosaccharide. AB - Chitosan-based amphiphilic graft copolymers are commonly obtained by modification of chitosan backbones with synthetic polymers hampering both bioactivity and biodegradability. In this work, we report the preparation of a series of chitosan oligosaccharide-grafted copolymers (PCL-g-COs) from coupling reactions between azide-pendent polycaprolactones (PCL-N3) and reducing-end alkynyl-modified chitosan oligosaccharides (COs-alkynyl). The resulting PCL-g-COs self-organized in water into nanoscale micelles (Rh<20 nm) having a COs shell and a PCL core. Locking of the core-micelles structure employing a disulfide-containing bis alkyne cross-linker resulted in the formation of nano-vehicles which can be degraded in response to physiological (redox) stimuli. This feature was advantageously exploited to preferentially release an anticancer drug, doxororubicin, in response to the intracellular glutathione level. PMID- 25129805 TI - Rheological study of chitosan acetate solutions containing chitin nanofibrils. AB - Rheological properties of chitosan acetate solutions containing chitin nanofibrils (n-chitin) and biocompatible plasticizers intended for preparation of biodegradable films are reported in the steady, oscillatory and transient shear flow. The experiments were performed on slurries with an optimum proportion of 65/35 wt.% between chitosan and n-chitin in the films which was determined from our results of mechanical properties and absorption of water vapor. The time dependent dynamic experiments revealed the chitin nanofibrils as an effective "gelling agent" of chitosan phase. The phenomenon is explained by a chitosan-like surface of n-chitin and by the interactions inducing orientational cooperativity of chitosan molecules dissolved in close neighborhood of the anisotropic chitin nanofibrils. Additions of glycerol or poly(ethylene glycol), improving mechanical properties of the films, delay significantly the onset of gelation of chitosan/n chitin slurries. The effect is induced by an increase in viscosity of the slurries and by their enhanced chaotropic character. PMID- 25129806 TI - Influence of feeding regimens on rat gut fluids and colonic metabolism of diclofenac-beta-cyclodextrin. AB - Feeding states may affect the performance of colonic prodrugs. The aim is to investigate the influence of feeding regimen in Wistar rats on: (i) distribution and pH contents along the gut and (ii) metabolism of two colonic prodrugs, diclofenac-beta-cyclodextrin and a commercially available control, sulfasalazine, within the caecal and colonic contents. Male Wistar rats were subject to four different feeding regimens, the gut contents characterized (mass and pH) and the metabolism of prodrugs investigated. The feeding regimen affects gut contents (mass and pH), more specifically in the stomach and lower intestine, and affects the rate of metabolism of diclofenac-beta-cyclodextrin, but not that of sulfasalazine. The latter's degradation is much faster than that of diclofenac beta-cyclodextrin while the metabolism of both prodrugs is faster in colonic (versus caecal) contents. Fasting results in most rapid degradation of diclofenac beta-cyclodextrin, possibly due to lack of competition (absence of food) for microbial enzymatic activity. PMID- 25129807 TI - Desipramine and citalopram attenuate pretest swim-induced increases in prodynorphin immunoreactivity in the dorsal bed nucleus of the stria terminalis and the lateral division of the central nucleus of the amygdala in the forced swimming test. AB - Dynorphin in the nucleus accumbens shell plays an important role in antidepressant-like effect in the forced swimming test (FST), but it is unclear whether desipramine and citalopram treatments alter prodynorphin levels in other brain areas. To explore this possibility, we injected mice with desipramine and citalopram 0.5, 19, and 23 h after a 15-min pretest swim and observed changes in prodynorphin expression before the test swim, which was conducted 24 h after the pretest swim. The pretest swim increased prodynorphin immunoreactivity in the dorsal bed nucleus of the stria terminalis (dBNST) and lateral division of the central nucleus of the amygdala (CeL). This increase in prodynorphin immunoreactivity in the dBNST and CeL was blocked by desipramine and citalopram treatments. Similar changes in prodynorphin mRNA levels were observed in the dBNST and CeL, but these changes did not reach significance. To understand the underlying mechanism, we assessed changes in phosphorylated CREB at Ser(133) (pCREB) immunoreactivity in the dBNST and central nucleus of the amygdala (CeA). Treatment with citalopram but not desipramine after the pretest swim significantly increased pCREB immunoreactivity only in the dBNST. These results suggest that regulation of prodynorphin in the dBNST and CeL before the test swim may be involved in the antidepressant-like effect of desipramine and citalopram in the FST and suggest that changes in pCREB immunoreactivity in these areas may not play an important role in the regulation of prodynorphin in the dBNST and CeA. PMID- 25129808 TI - Enhancing the efficiency of direct reprogramming of human primary fibroblasts into dopaminergic neuron-like cells through p53 suppression. AB - Dopaminergic (DA) neuron-like cells obtained through direct reprogramming of primary human fibroblasts offer exciting opportunities for treatment of Parkinson's disease. A significant obstacle is the low efficiency of conversion during the reprogramming process. Here, we demonstrate that the suppression of p53 significantly enhances the efficiency of transcription factor-mediated conversion of human fibroblasts into functional dopaminergic neurons. In particular, blocking p53 activity using a dominant-negative p53 (p53-DN) in IMR90 cells increases the conversion efficiency by 5-20 fold. The induced DA neuron like cells exhibit dopamine neuron-specific gene expression, significant dopamine uptake and production capacities, and enables symptomatic relief in a rat Parkinson's disease model. Taken together, our findings suggest that p53 is a critical barrier in direct reprogramming of fibroblast into dopaminergic neurons. PMID- 25129809 TI - No correlation between the diversity and productivity of assemblages: evidence from the phytophage and predator assemblages in various cotton agroecosystems. AB - Biodiversity research has shown that primary productivity increases with plant species number, especially in many experimental grassland systems. Here, we assessed the correlation between productivity and diversity of phytophages and natural enemy assemblages associated with planting date and intercropping in four cotton agroecosystems. Twenty-one pairs of data were used to determine Pearson correlations between species richness, total number of individuals, diversity indices and productivity for each assemblage every five days from 5 June to 15 September 2012. At the same trophic level, the productivity exhibited a significant positive correlation with species richness of the phytophage or predator assemblage. A significant correlation was found between productivity and total number of individuals in most cotton fields. However, no significant correlations were observed between productivity and diversity indices (including indices of energy flow diversity and numerical diversity) in most cotton fields for either the phytophage or the predator assemblages. Species richness of phytophage assemblage and total individual numbers were significantly correlated with primary productivity. Also, species richness of natural enemy assemblage and total number of individuals correlated with phytophage assemblage productivity. A negative but not significant correlation occurred between the indices of numerical diversity and energy flow diversity and lower trophic-level productivity in the cotton-phytophage and phytophage-predator assemblages for most intercropped cotton agroecosystems. Our results clearly showed that there were no correlations between diversity indices and productivity within the same or lower trophic levels within the phytophage and predator assemblages in cotton agroecosystems, and inter-cropped cotton fields had a stronger ability to support the natural enemy assemblage and potentially to reduce phytophages. PMID- 25129810 TI - False memories to emotional stimuli are not equally affected in right- and left brain-damaged stroke patients. AB - Previous research has attributed to the right hemisphere (RH) a key role in eliciting false memories to visual emotional stimuli. These results have been explained in terms of two right-hemisphere properties: (i) that emotional stimuli are preferentially processed in the RH and (ii) that visual stimuli are represented more coarsely in the RH. According to this account, false emotional memories are preferentially produced in the RH because emotional stimuli are both more strongly and more diffusely activated during encoding, leaving a memory trace that can be erroneously reactivated by similar but unstudied emotional items at test. If this right-hemisphere hypothesis is correct, then RH damage should result in a reduction in false memories to emotional stimuli relative to left-hemisphere lesions. To investigate this possibility, groups of right-brain damaged (RBD, N=15), left-brain-damaged (LBD, N=15) and healthy (HC, N=30) participants took part in a recognition memory experiment with emotional (negative and positive) and non-emotional pictures. False memories were operationalized as incorrect responses to unstudied pictures that were similar to studied ones. Both RBD and LBD participants showed similar reductions in false memories for negative pictures relative to controls. For positive pictures, however, false memories were reduced only in RBD patients. The results provide only partial support for the right-hemisphere hypothesis and suggest that inter hemispheric cooperation models may be necessary to fully account for false emotional memories. PMID- 25129811 TI - Combination effects of baicalein with antibiotics against oral pathogens. AB - BACKGROUND: Baicalein is one of the major flavonoids in Scutellaria baicalensis Georgi, which has long been used in Asia as herbal medicine. Several biological effects of baicalein, such as antiviral, anti-inflammatiom, anti-hepatotoxicity, and anti-tumour properties, have been reported. OBJECTIVE AND DESIGN: In this study, the antibacterial activities of baicalein were investigated in combination with ampicillin and/or gentamicin against oral bacteria. RESULTS: Baicalein was determined with MIC and MBC values ranging from 80 to 320 and 160 to 640 MUg/mL against oral bacteria. The range of MIC50 and MIC90 were 20-160 MUg/mL and 80-320 MUg/mL, respectively. The combination effects of baicalein with antibiotics were synergistic (FIC index <0.375-0.5 and FBCI <0.5) against oral bacteria. Furthermore, a time-kill study showed that the growth of the tested bacteria was completely attenuated after 1-6 h of treatment with the MIC50 of baicalein, regardless of whether it was administered alone or with ampicillin or gentamicin. CONCLUSION: These results suggest that baicalein combined with other antibiotics may be microbiologically beneficial and not antagonistic. PMID- 25129812 TI - Effect of radiotherapy on the eruption rate and morphology of the odontogenic region of rat incisors. AB - OBJECTIVE: The goal in this study was to evaluate the results of doses of 5 and 15 Gy of radiation in odontogenic region of the rats inferior mandibular-incisors by a histological analysis and the rate of eruptions. DESIGN: Animals were divided into three groups: control, radiotherapy 5 Gy and radiotherapy 15 Gy. In which tooth-eruption-rate was measured every two days. RESULTS: Animals in Group 5 Gy presented values similar to those of the control group. Animals in Group 15 Gy presented reduction in tooth-eruption-rate as of the sixth day of the experiment, vast disorganization of odontoblasts and ameloblasts, apparent reduction in cell population in the follicle region and alterations in cervical loop formation of the dental organ. CONCLUSIONS: It was concluded that there was a difference between the researched doses, and histological alteration at 15 Gy lead to statistical reduction in tooth-eruption-rate. PMID- 25129813 TI - Metal splinter ejected by circular saw into the left ventricle. AB - We report a case of a metal splinter ejected by a circular saw tooth from a wooden board into the left ventricle of the heart. A 35-year old man was admitted second day after accident attributed to work complaining about general weakness. Only a small non-bleeding wound was found near his sternum. CT scan showed a metal wire entrapped inside his heart. Successful removal was done during surgery. PMID- 25129814 TI - What is the value of topical cooling as an adjunct to myocardial protection? AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'What is the value of topical cooling as an adjunct to myocardial protection?' Using the reported search, 9 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The studies included four randomized controlled trials (RCTs). Two RCTs demonstrated no cardioprotective effects of topical hypothermia as they found no statistically significant differences in myocardial markers between patients with or without topical cooling. In a randomized study of 249 patients undergoing elective cardiac surgery, phrenic nerve injury and failure of extubation occurred more frequently with the use of topical hypothermia with iced slush (P = 0.009 and P = 0.034, respectively). One retrospective analysis found that patients who received iced topical hypothermia had longer postoperative hospitalization, higher incidence of atelectasis and higher left diaphragms on chest X-ray. Another study showed increased morbidity and mortality associated with postoperative diaphragmatic dysfunction resulting from the use of iced slush topical cooling of the heart. We conclude that topical cooling is an unnecessary adjunct to myocardial protection in patients undergoing cardiac surgery. There is no evidence of any additional cardioprotective benefit. Several studies showed that the use of topical hypothermia is associated with phrenic nerve injury, leading to diaphragmatic paralysis and increased pulmonary complications. Moreover, long term follow-up data showed often incomplete regression of the phrenic nerve paralysis. However, few randomized studies exist on the value of topical cooling as an adjunct to myocardial protection. PMID- 25129815 TI - Motivational interviewing in permanent supportive housing: the role of organizational culture. AB - This study evaluated motivational interviewing (MI) in a permanent supportive housing agency. The agency's contradictory social service and business missions resulted in an incompatible organizational culture theorized to diminish MI's effectiveness. A combination of observational, interview, and archival data collected over 3 years were used to examine MI implementation within an incompatible supportive housing agency. Two major themes arose: how MI is used to categorize and change clients in permanent supportive housing and how worker worker relationships affect MI implementation. The results suggest that within incompatible organizational environments, key elements of effective MI implementation are greatly weakened. PMID- 25129816 TI - Phases and phase transition in insoluble and adsorbed monolayers of amide amphiphiles: Specific characteristics of the condensed phases. AB - For understanding the role of amide containing amphiphiles in inherently complex biological processes, monolayers at the air-water interface are used as simple biomimetic model systems. The specific characteristics of the condensed phases and phase transition in insoluble and adsorbed monolayers of amide amphiphiles are surveyed to highlight the effect of the chemical structure of the amide amphiphiles on the interfacial interactions in model monolayers. The mesoscopic topography and/or two-dimensional lattice structures of selected amino acid amphiphiles, amphiphilic N-alkylaldonamide, amide amphiphiles with specific tailored headgroups, such as amide amphiphiles based on derivatized ethanolamine, e.g. acylethanolamines (NAEs) and N-,O-diacylethanolamines (DAEs) are presented. Special attention is devoted the dominance of N,O-diacylated ethanolamine in mixed amphiphilic acid amide monolayers. The evidence that a first order phase transition can occur in adsorption layers and that condensed phase domains of mesoscopic scale can be formed in adsorption layers was first obtained on the basis of the experimental characteristics of a tailored amide amphiphile. New thermodynamic and kinetic concepts for the theoretical description of the characteristics of amide amphiphile's monolayers were developed. In particular, the equation of state for Langmuir monolayers generalized for the case that one, two or more phase transitions occur, and the new theory for phase transition in adsorbed monolayers are experimentally confirmed at first by amide amphiphile monolayers. Despite the significant progress made towards the understanding the model systems, these model studies are still limited to transfer the gained knowledge to biological systems where the fundamental physical principles are operative in the same way. The study of biomimetic systems, as described in this review, is only a first step in this direction. PMID- 25129817 TI - Hard scalp lump with headache. PMID- 25129819 TI - Malnutrition among cognitively intact, noncritically ill older adults in the emergency department. AB - STUDY OBJECTIVE: We estimate the prevalence of malnutrition among older patients presenting to an emergency department (ED) in the southeastern United States and identify subgroups at increased risk. METHODS: We conducted a cross-sectional study with random time block sampling of cognitively intact patients aged 65 years and older. Nutrition was assessed with the Mini Nutritional Assessment Short-Form (0 to 14 scale), with malnutrition defined as a score of 7 or less and at risk for malnutrition defined as a score of 8 to 11. The presence of depressive symptoms was defined as a Center for Epidemiological Studies Depression-10 score of 4 or more (0 to 10 scale). RESULTS: Among 138 older adults, 16% (95% confidence interval [CI] 11% to 23%) were malnourished and 60% (95% CI 52% to 68%) were either malnourished or at risk for malnutrition. Seventeen of the 22 malnourished patients (77%) denied previously receiving a diagnosis of malnutrition. The prevalence of malnutrition was not appreciably different between men and women, across levels of patient education, or between those living in urban and rural areas. However, the prevalence of malnutrition was higher among patients with depressive symptoms (52%), those residing in assisted living (44%), those with difficulty eating (38%), and those reporting difficulty buying groceries (33%). CONCLUSION: Among a random sample of cognitively intact older ED patients, more than half were malnourished or at risk for malnutrition, and the majority of malnourished patients had not previously received a diagnosis. Higher rates of malnutrition among individuals with depression, difficulty eating, and difficulty buying groceries suggest the need to explore multifaceted interventions. PMID- 25129820 TI - Efficacy and safety of out-of-hospital intravenous metoprolol administration in anterior ST-segment elevation acute myocardial infarction: insights from the METOCARD-CNIC trial. AB - STUDY OBJECTIVE: We seek to examine the efficacy and safety of prereperfusion emergency medical services (EMS)-administered intravenous metoprolol in anterior ST-segment elevation myocardial infarction patients undergoing eventual primary angioplasty. METHODS: This is a prespecified subgroup analysis of the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial population, who all eventually received oral metoprolol within 12 to 24 hours. We studied patients receiving intravenous metoprolol by EMS and compared them with others treated by EMS but not receiving intravenous metoprolol. Outcomes included infarct size and left ventricular ejection fraction on cardiac magnetic resonance imaging at 1 week, and safety by measuring the incidence of the predefined combined endpoint (composite of death, malignant ventricular arrhythmias, advanced atrioventricular block, cardiogenic shock, or reinfarction) within the first 24 hours. RESULTS: From the total population of the trial (N=270), 147 patients (54%) were recruited during out-of-hospital assistance and transferred to the primary angioplasty center (74 intravenous metoprolol and 73 controls). Infarct size was smaller in patients receiving intravenous metoprolol compared with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference -11.4; 95% confidence interval [CI] -18.6 to -4.3). Left ventricular ejection fraction was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD 10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration did not increase the incidence of the prespecified safety combined endpoint: 6.8% versus 17.8% in controls (risk difference -11.1; 95% CI -21.5 to -0.6). CONCLUSION: Out-of-hospital administration of intravenous metoprolol by EMS within 4.5 hours of symptom onset in our subjects reduced infarct size and improved left ventricular ejection fraction with no excess of adverse events during the first 24 hours. PMID- 25129822 TI - Cellular domains and viral lineages. AB - It has been claimed that giant DNA viruses represent a separate, fourth domain of life in addition to the domains of Bacteria, Archaea, and Eukarya. Such classification disregards fundamental differences between the two types of living entities - viruses and cells - and results in confusion and controversies in evolutionary scenarios. We highlight these problems and emphasize the importance of restricting the term 'domain' to the descendants of the last universal cellular ancestor (LUCA), based on the shared ribosome structure. We suggest tracing phylogeny of viruses along evolutionary lineages primarily defined by virion architectures and the structures of the major capsid proteins. PMID- 25129821 TI - DJ-1: a promising marker in metastatic uveal melanoma. AB - PURPOSE: Overexpression of DJ-1 was associated with metastatic uveal melanoma (UM). The purpose of this study was to evaluate the potential of serum DJ-1 as a biomarker for metastasis of uveal melanoma. METHODS: Serum DJ-1 levels were determined by ELISA assays in 27 patients with metastatic UM metastatic uveal melanoma and in 76 patients who were disease free for at least 10 years and 30 age- and sex-matched controls. Receiver operating characteristic (ROC) curve was used to evaluate the feasibility of DJ-1 in detection of metastatic uveal melanoma. RESULTS: Serum DJ-1 levels were significantly higher in patients with metastatic UM compared with patients who were disease free for at least 10 years (P < 0.001) or with controls (P < 0.001). ROC curve for DJ-1 revealed an area under the curve of 86.3%, and when 3.350 ng/mL was used as the cutoff value, a sensitivity of 74.1% and a specificity of 94.3% were achieved. Comparison of DJ-1 and liver function tests (LFTs) ROC curves indicated that DJ-1 was superior to LFTs in detection of metastatic UM. CONCLUSIONS: Our data suggest that DJ-1 might be a promising serum marker for monitoring metastatic uveal melanoma. PMID- 25129823 TI - Microbial communities associated with human decomposition and their potential use as postmortem clocks. AB - Most forensic research that is used to better understand how to estimate the postmortem interval (PMI) entails the study of the physiochemical characteristics of decomposition and the effects that environmental factors have on the decomposition process. Forensic entomology exploits the life cycles of arthropods like Diptera (blow flies or flesh flies) and Coleoptera (beetles) deposited on the decaying carcass to determine PMI. Forensic taphonomy, from the Greek word taphos meaning burial, studies the creation of the fossils of decomposed cadavers to ascertain information as to the nature and time of death. Compared to other areas of taphonomy, there have been relatively few forensic science studies that have investigated the impact of human decomposition on the microbial changes occurring on or in a corpse or in the soil communities underneath a body. Such research may facilitate the critical determination of PMI. Therefore, the scope of this review is to provide a concise summary of the current progress in the newly emerging field of microbial diversity and the next-generation metagenomic sequencing approaches for assessing these communities in humans and in the soil beneath decomposing human. PMID- 25129824 TI - Motivational Profiles of Gambling Behavior: Self-determination Theory, Gambling Motives, and Gambling Behavior. AB - Gambling among young adults occurs at a higher rate than in the general population and is associated with a host of negative consequences. Self determination theory (SDT) posits that individuals develop general motivational orientations which predict a range of behavioral outcomes. An autonomy orientation portrays a choiceful perspective facilitating personal growth, whereas a controlled orientation represents a chronic proclivity toward external pressures and a general lack of choice. Further, an impersonal orientation is characterized by alack of intention and feeling despondent and ineffective. Controlled orientation has previously been associated with more frequent and problematic gambling. This research was designed to examine gambling motives as mediators of associations between motivational orientations and gambling behaviors. Undergraduates (N = 252) who met 2+ criteria on the South Oaks Gambling Screen participated in a laboratory survey assessing their motivational orientations, gambling motives, and gambling behavior (quantity, frequency, and problems). Mediation analyses suggested that autonomy was negatively associated with gambling problems through lower levels of chasing and escape motives. Further, controlled orientation was associated with more problems through higher levels of chasing and interest motives. Finally, impersonal orientation was negatively associated with amount won through escape motives. Overall, results support exploring gambling behavior and motives using a SDT framework. PMID- 25129825 TI - Magnetic resonance perfusion and diffusion imaging characteristics of transient bone marrow edema, avascular necrosis and subchondral insufficiency fractures of the proximal femur. AB - PURPOSE: To evaluate magnetic resonance (MR) perfusion and diffusion imaging characteristics in patients with transient bone marrow edema (TBME), avascular necrosis (AVN), or subchondral insufficiency fractures (SIF) of the proximal femur. MATERIALS AND METHODS: 29 patients with painful hip and bone marrow edema pattern of the proximal femur on non-contrast MR imaging were examined using diffusion-weighted and dynamic gadolinium-enhanced sequences. Apparent diffusion coefficients (ADCs) and perfusion parameters were calculated for different regions of the proximal femur. Regional distribution and differences in ADC values and perfusion parameters were evaluated. RESULTS: Seven patients presented with TBME, 15 with AVN and seven with SIF of the proximal femur. Perfusion imaging showed significant differences for maximum enhancement values (Emax), slope (Eslope) and time to peak (TTP) between the three patient groups (p<0.05). In contrast, no significant differences for ADC values were calculated when comparing TBME, AVN, and SIF patients. CONCLUSION: Diffusion weighted imaging of bone marrow of the proximal femur did not show significant differences between patients with TBME, AVN or SIF. In contrast, MR perfusion imaging demonstrated significant differences for the different patient groups and may as a complementary imaging technique add information to the understanding of the pathophysiology of diseases associated with bone marrow edema. PMID- 25129826 TI - Involvement of threonine deaminase FgIlv1 in isoleucine biosynthesis and full virulence in Fusarium graminearum. AB - In this study we characterized FgIlv1, a homologue of the Saccharomyces cerevisiae threonine dehydratase (TD) from the important Fusarium head blight fungus Fusarium graminearum. TD catalyzes the first step in the biosynthesis pathway of isoleucine (Ile) for conversion of threonine (Thr) to 2-ketobutyrate (2-KB). The FgILV1 deletion mutant DeltaFgIlv1-3 was unable to grow on minimal medium or fructose gelatin agar which lacked Ile. Exogenous supplementation of Ile or 2-KB but not Thr rescued the mycelial growth defect of DeltaFgIlv1-3, indicating the involvement of FgIlv1 in the conversion of Thr to 2-KB in Ile biosynthesis. Additionally, exogenous supplementation of Methionine (Met) could also rescue the mycelial growth defect of DeltaFgIlv1-3, indicating a crosstalk between Ile biosynthesis and Met catabolism in F. graminearum. Deletion of FgILV1 also caused defects in conidial formation and germination. In addition, DeltaFgIlv1-3 displayed decreased virulence on wheat heads and a low level of deoxynivalenol (DON) production in wheat kernels. Taken together, results of this study indicate that FgIlv1 is an essential component in Ile biosynthesis and is required for various cellular processes including mycelial and conidial morphogenesis, DON biosynthesis, and full virulence in F. graminearum. Our data indicate the potential of targeting Ile biosynthesis for anti-FHB management. PMID- 25129827 TI - In vitro properties of apheresis platelet during extended storage in plasma treated with anandamide. AB - BACKGROUND: In China apheresis platelets (PLTs) are stored in plasma for only 5 days, resulting in PLT inventory pressures. Anandamide (ANA) was reported to be a potential agent to inhibit PLT apoptosis. The aim of this study was to evaluate the characteristics of extended storage PLTs in plasma treated with ANA in vitro. METHODS: Apheresis PLTs (n = 20) were prepared in plasma treated with ANA, and stored at 22 degrees C for up to 11 days. On day 1, 3, 5, 7, 9 and 11, PLTs were tested for PLT count, mean PLT volume (MPV), PLT distribution width (PDW), pH, pCO(2), pO(2), hypotonic shock response (HSR), phosphatidylserine (PS) exposure and soluble P-selectin content. RESULTS: PLTs stored in plasma with/without ANA didn't show significant differences during the first 5 days of storage. From the 7(th) day on, PLTs stored in plasma with ANA displayed significantly lower PS expression, soluble P-selectin content and higher HSR scores than those stored in plasma without ANA (P <0.05), respectively. CONCLUSION: The extended storage of PLTs in plasma treated with 0.5 umol/l ANA showed better characteristics of the PLTs, compared with the control group, which was suggested to potentially alleviate the PLT storage lesion. PMID- 25129828 TI - Treatment of steroid resistant ulcerative colitis with severe autoimmune haemolytic anaemia. PMID- 25129829 TI - Use of aprotinin to reduce blood loss and transfusion in major orthopedic surgery: a meta-analysis. AB - BACKGROUD: Conflicting reports have been published regarding the effectiveness and safety of aprotinin in reducing blood loss and transfusion in patients undergoing orthopedic surgery. We performed a meta-analysis to evaluate the effectiveness and safety of aprotinin in reducing blood loss and transfusion in major orthopedic surgery. MATERIALS AND METHODS: MEDLINE, PubMed, EMBASE and Cochrane databases were searched for relevant studies. Only randomized controlled trials were eligible for this study. The weighted mean difference in blood loss, and number of transfusions per patient and the summary risk ratio of transfusion requirements, and deep-vein thrombosis (DVT) were calculated in the aprotinin treated group and the control group. RESULTS: Eighteen randomized controlled trials involving 1276 patients were included. The use of aprotinin reduced total blood loss by a mean of 498.88 ml (95% confidence interval [CI]; -735.03 to 262.72), intra-operative blood loss by a mean of 246.11 ml (95% CI; -352.11 to 140.11), post-operative blood loss by a mean of 169.11 ml (95% CI; -234.06 to 105.55), the number of blood transfusions per patient by 0.93 units (95% CI; 1.36 to -0.51). Aprotinin led to a signficant reduction in transfusion requirements (RR 0.59; 95% CI; 0.51 to 0.69) and no increase in the risk of DVT (RR 0.58; 95% CI; 0.38 to 1.08). CONCLUSION: The meta-analysis shows that aprotinin could significantly reduce blood loss and blood transfusion requirements in patients undergoing orthopedic surgery, and it did not appear to increase the risk of DVT. PMID- 25129830 TI - Response to Al-Khabori M. et al.'s "validation of a non-invasive pulse CO oximetry based hemoglobin estimation in normal blood donors," Transfusion and Apheresis Science 2013 Nov 4. Accurate enough for blood donors? Not so fast. PMID- 25129832 TI - Relationship between protozoan and metazoan communities and operation and performance parameters in a textile sewage activated sludge system. AB - The present study aims at investigating the possibility of assessing performance and depuration conditions of an activated sludge wastewater treatment plant through an exploration of the microfauna. The plant, receiving textile industrial (70%) and domestic (30%) sewage, consists of a two-step biological depurating plant, with activated sludge followed by a percolating system. A total of 35 samples were analyzed during five months, and 30 taxa of protozoa and small metazoa were found. Epistylis rotans, Vorticella microstoma, Aspidisca cicada and Arcella sp. were the most frequent protozoa identified. Several significant correlations between biological, physical-chemical and operational parameters were determined, but no significant correlations could be established between biological parameters and removal efficiencies. The Sludge Biotic Index (SBI) reflected the overall state of the community but only presented statistically significant correlations with the influent total suspended solids (TSS), total suspended solids in mixed-liquor (MLTSS) and dissolved oxygen (DO). The determination of key groups and taxa along with general community parameters showed to have potential value as indicators of the depuration conditions. Despite the impossibility of correlating biological parameters and the removal efficiencies, the present study attests the value of the microfauna to assess the operation of the activated sludge systems even in the case of non-conventional plants and/or plants receiving industrial sewage. PMID- 25129833 TI - Multivariate morphometric analyses of the predatory ciliate genus Semispathidium (Ciliophora: Litostomatea), with description of S. longiarmatum nov. spec. AB - We studied morphometrical variation, species boundaries, and importance of morphometric features for a reliable separation of five African Semispathidium taxa. Altogether, 20 features traditionally used in alpha-taxonomy of the predatory genus Semispathidium were measured or scored on 85 protargol impregnated interphase specimens, and were analyzed using hierarchical clustering as well as principal component and canonical discriminant analyses. This multivariate approach confirmed that a population found in Botswanan floodplain soil represents a distinct taxon. The new species is described here as S. longiarmatum, using live observation, protargol impregnation, and scanning electron microscopy. Semispathidium longiarmatum strongly resembles S. armatum and S. breviarmatum but it is clearly distinguished from these species by the extrusome pattern. The reliability of S. longiarmatum is also strengthened, according to the canonical discriminant analysis, by several quantitative features, viz., the number of ciliary rows, the length:width ratio of the macronucleus, and the number of dikinetids in brush row 1. Moreover, the present study documents the distinctness of all African Semispathidium species which can be separated by a combination of both qualitative and quantitative (morphometric) features. Consequently, Semispathidium species do not form a continuous complex but fairly discrete clusters in the phenotypic space. PMID- 25129831 TI - Childhood infections and trauma as risk factors for stroke. AB - Stroke is as common as brain tumor in children. The etiology of childhood arterial ischemic stroke (AIS) appears to be multifactorial, resulting from the interaction between genetic predisposition and environmental triggers. The risk factors for AIS in children are markedly different from the atherosclerotic risk factors in adults. Trauma and infections have been identified as associations in previous studies and are exposures of particular interest because of their increased prevalence in the children. The aim of this review article is to provide an overview of the research studies that have addressed the role of infections and trauma in pediatric AIS. PMID- 25129834 TI - Colonization dynamics of ciliate morphotypes modified by shifting sandy sediments. AB - Sandy stream-bed sediments colonized by a diverse ciliate community are subject to various disturbance regimes. In microcosms, we investigated the effect of sediment shifting on the colonization dynamics of 3 ciliate morphotypes differing in morphology, behavior and feeding strategy. The dynamics of the ciliate morphotypes inhabiting sediment pore water and overlying water were observed at 3 sediment shifting frequencies: (1) stable sediments, (2) periodically shifting sediments such as migrating ripples, and (3) continuously shifting sediments as occurring during scour events of the uppermost sediment. Sediment shifting significantly affected the abundance and growth rate of the ciliate morphotypes. The free-swimming filter feeder Dexiostoma campylum was vulnerable to washout by sediment shifting since significantly higher numbers occurred in the overlying water than in pore water. Abundance of D. campylum only increased in pore water of stable sediments. On the contrary, the vagile grasper feeder Chilodonella uncinata and the sessile filter feeder Vorticella convallaria had positive growth rates and successfully colonized sediments that shifted periodically and continuously. Thus, the spatio-temporal pattern of sediment dynamics acts as an essential factor of impact on the structure, distribution and function of ciliate communities in sand-bed streams. PMID- 25129835 TI - Redescription of Atopospira galeata (Kahl, 1927) nov. comb. and A. violacea (Kahl, 1926) nov. comb. with redefinition of Atopospira Jankowski, 1964 nov. stat. and Brachonella Jankowski, 1964 (Ciliophora, Armophorida). AB - The taxonomy of the Metopidae (Ciliophora, Armophorida) remains poorly understood since most of its members have not been studied by modern morphologic and molecular methods. Recent molecular investigations have indicated that the two most species-rich genera, Metopus and Brachonella, are likely nonmonophyletic with at least one well-supported 18S rDNA clade comprised of a species from each of these genera (Brachonella galeata and Metopus violaceus). We investigated these two species with silver impregnation and scanning electron microscopy. Both taxa share important morphologic characteristics not described in other species of Metopus or Brachonella. These synapomorphies include: (1) a diplostichomonad paroral membrane, (2) a bipartite adoral zone with a short buccal part composed of ordinary membranelles and a longer distal part composed of much smaller membranelles bearing a single cilium or none and extending the same length as the perzonal ciliary stripe. We transfer Brachonella galeata (Kahl, 1927) Jankowski, 1964 and Metopus violaceus Kahl, 1926 to genus Atopospira Jankowski, 1964 nov. stat. Pending detailed morphologic and molecular characterization, Brachonella campanula, B. cydonia and B. pyriforma, B. intercedens, and B. lemani remain in Brachonella Jankowski 1964. PMID- 25129836 TI - Morphology of Clapsiella magnifica gen. n., sp. n., a new hypotrichous ciliate with a curious dorsal ciliary pattern. AB - The present work describes the morphology and infraciliature of a new hypotrichous ciliate, Clapsiella magnifica gen. n., sp. n., found in rewetted soil from a temporal pond in Argentina. It was studied by means of live observation and protargol impregnation. Its main diagnostic features are: Flexible hypotrich measuring 250-320 MUm * 70-140 MUm in vivo; two macronuclear nodules and 4-6 micronuclei. Single contractile vacuole. Cytoplasm transparent, cortical granules absent. Somatic ciliature composed of a tricorona of cirri, three buccal(?) cirri, 6-9 ventral rows, 3-5 right marginal(?) rows, one left marginal row, and 12-17 transverse cirri. Dorsal pattern rather complicated, with about 14 kineties and kinety fragments, with scattered kinetids among them; 17-28 caudal cirri arranged in three rows on dorsal kineties 1, 3, and 7. Remarkably, dorsal kinetids have two or four basal bodies, bearing a stiff bristle arising from left anterior basal body. Adoral zone composed of 70-92 membranelles, occupying about 40% of body length in protargol preparations; paroral and endoral curved, resembling a cyrtohymenid pattern. The peculiar dorsal ciliary arrangement and the unique combination of other characters require the establishment of a new genus for this new species, which is considered incertae sedis in the Hypotricha but possibly related to the oxytrichids. PMID- 25129837 TI - Ciliate communities of a large shallow lake: association with macrophyte beds. AB - We investigated the influence of macrophyte composition on ciliate community structure in a large, shallow, eutrophic Lake Vortsjarv. We hypothesized that macrophyte composition must have strong influence on the dispersal of ecologically different ciliate groups in a shallow lake and that more diverse macrophyte stands cause also a greater diversity in the ciliate community. In Vortsjarv macrophyte distribution is spatially strongly polarized both in east west and north-south directions in relation to abiotic factors. Phragmites australis and Myriophyllum spicatum were the most widespread species occurring in most parts of the lake. Correlation of environmental, macrophyte and planktonic ciliate variables confirmed the suggested spatial gradients. More diverse macrophyte stands supported a high species richness and abundance of epiplanktonic community but showed negative influence on the number and abundance of euplanktonic ciliate taxa. Opposite trends were found relative to the abundance of P. australis. Benthic ciliates showed a similar distribution pattern to euplanktonic taxa being most abundant in sites were the Shannon-Weaver index for macrophytes was low. Strong polarizing effect of the lake's vegetation on planktonic ciliate diversity was reflected in correlations of the number of ciliate taxa as well as the numbers of eu- and epiplanktonic taxa with geographic co-ordinates. PMID- 25129838 TI - Diurnal and twenty-four hour patterning of human diseases: cardiac, vascular, and respiratory diseases, conditions, and syndromes. AB - Various medical conditions, disorders, and syndromes exhibit predictable-in-time diurnal and 24 h patterning in the signs, symptoms, and grave nonfatal and fatal events, e.g., respiratory ones of viral and allergic rhinorrhea, reversible (asthma) and non-reversible (bronchitis and emphysema) chronic obstructive pulmonary disease, cystic fibrosis, high altitude pulmonary edema, and decompression sickness; cardiac ones of atrial premature beats and tachycardia, paroxysmal atrial fibrillation, 3rd degree atrial-ventricular block, paroxysmal supraventricular tachycardia, ventricular premature beats, ventricular tachyarrhythmia, symptomatic and non-symptomatic angina pectoris, Prinzmetal vasospastic variant angina, acute (non-fatal and fatal) incidents of myocardial infarction, sudden cardiac arrest, in-bed sudden death syndrome of type-1 diabetes, acute cardiogenic pulmonary edema, and heart failure; vascular and circulatory system ones of hypertension, acute orthostatic postprandial, micturition, and defecation hypotension/syncope, intermittent claudication, venous insufficiency, standing occupation leg edema, arterial and venous branch occlusion of the eye, menopausal hot flash, sickle cell syndrome, abdominal, aortic, and thoracic dissections, pulmonary thromboembolism, and deep venous thrombosis, and cerebrovascular transient ischemic attack and hemorrhagic and ischemic stroke. Knowledge of these temporal patterns not only helps guide patient care but research of their underlying endogenous mechanisms, i.e., circadian and others, and external triggers plus informs the development and application of effective chronopreventive and chronotherapeutic strategies. PMID- 25129839 TI - Diurnal and twenty-four hour patterning of human diseases: acute and chronic common and uncommon medical conditions. AB - The symptom intensity and mortality of human diseases, conditions, and syndromes exhibit diurnal or 24 h patterning, e.g., skin: atopic dermatitis, urticaria, psoriasis, and palmar hyperhidrosis; gastrointestinal: esophageal reflux, peptic ulcer (including perforation and hemorrhage), cyclic vomiting syndrome, biliary colic, hepatic variceal hemorrhage, and proctalgia fugax; infection: susceptibility, fever, and mortality; neural: frontal, parietal, temporal, and occipital lobe seizures, Parkinson's and Alzheimer's disease, hereditary progressive dystonia, and pain (cancer, post-surgical, diabetic neuropathic and foot ulcer, tooth caries, burning mouth and temporomandibular syndromes, fibromyalgia, sciatica, intervertebral vacuum phenomenon, multiple sclerosis muscle spasm, and migraine, tension, cluster, hypnic, and paroxysmal hemicranial headache); renal: colic and nocturnal enuresis and polyuria; ocular: bulbar conjunctival redness, keratoconjunctivitis sicca, intraocular pressure and anterior ischemic optic neuropathy, and recurrent corneal erosion syndrome; psychiatric/behavioral: major and seasonal affective depressive disorders, bipolar disorder, parasuicide and suicide, dementia-associated agitation, and addictive alcohol, tobacco, and heroin cravings and withdrawal phenomena; plus autoimmune and musculoskeletal: rheumatoid arthritis, osteoarthritis, axial spondylarthritis, gout, Sjogren's syndrome, and systemic lupus erythematosus. Knowledge of these and other 24 h patterns of human pathophysiology informs research of their underlying circadian and other endogenous mechanisms, external temporal triggers, and more effective patient care entailing clinical chronopreventive and chronotherapeutic strategies. PMID- 25129840 TI - [Crystalluria in ethylene glycol intoxication]. AB - When seen, some habits of calcium oxalate monohydrate crystals (whewellite) are so typical of ethylene glycol intoxication that they may be helpful for its diagnosis when circumstances are not clearly established. PMID- 25129841 TI - IT Infrastructure to support the secondary use of routinely acquired clinical imaging data for research. AB - We propose an infrastructure for the automated anonymization, extraction and processing of image data stored in clinical data repositories to make routinely acquired imaging data available for research purposes. The automated system, which was tested in the context of analyzing routinely acquired MR brain imaging data, consists of four modules: subject selection using PACS query, anonymization of privacy sensitive information and removal of facial features, quality assurance on DICOM header and image information, and quantitative imaging biomarker extraction. In total, 1,616 examinations were selected based on the following MRI scanning protocols: dementia protocol (246), multiple sclerosis protocol (446) and open question protocol (924). We evaluated the effectiveness of the infrastructure in accessing and successfully extracting biomarkers from routinely acquired clinical imaging data. To examine the validity, we compared brain volumes between patient groups with positive and negative diagnosis, according to the patient reports. Overall, success rates of image data retrieval and automatic processing were 82.5 %, 82.3 % and 66.2 % for the three protocol groups respectively, indicating that a large percentage of routinely acquired clinical imaging data can be used for brain volumetry research, despite image heterogeneity. In line with the literature, brain volumes were found to be significantly smaller (p-value <0.001) in patients with a positive diagnosis of dementia (915 ml) compared to patients with a negative diagnosis (939 ml). This study demonstrates that quantitative image biomarkers such as intracranial and brain volume can be extracted from routinely acquired clinical imaging data. This enables secondary use of clinical images for research into quantitative biomarkers at a hitherto unprecedented scale. PMID- 25129842 TI - Shwachman-Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease. AB - Liver abnormalities that normalize during infancy as well an enteropathy are reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions is unknown. We report two SDS cases with autoimmune-like (antismooth muscle and/or antinuclear antibody positivity) liver disease and antigliadin antibody positive inflammatory enteropathy. Hypertransaminasemia did not resolve after immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune phenomena and gut-liver axis perturbations may have played a role in transient SDS hepatopathy and enteropathy. Our report may stimulate other studies to define the relationship between the SDS genetic defect and intestinal permeability as the pathogenic mechanism underlying SDS related liver and intestinal inflammation. PMID- 25129843 TI - Ertapenem induced hyperbilirubinemia. PMID- 25129845 TI - Is guava phenolic metabolism influenced by elevated atmospheric CO2? AB - Seedlings of Psidium guajava cv. Pedro Sato were distributed into four open-top chambers: two with ambient CO(2) (~390 ppm) and two with elevated CO(2) (~780 ppm). Monthly, five individuals of each chamber were collected, separated into root, stem and leaves and immediately frozen in liquid nitrogen. Chemical parameters were analyzed to investigate how guava invests the surplus carbon. For all classes of phenolic compounds analyzed only tannins showed significant increase in plants at elevated CO(2) after 90 days. There was no significant difference in dry biomass, but the leaves showed high accumulation of starch under elevated CO(2). Results suggest that elevated CO(2) seems to be favorable to seedlings of P. guajava, due to accumulation of starch and tannins, the latter being an important anti-herbivore substance. PMID- 25129846 TI - Resolution of airflow obstruction on polysomnography after laryngotracheal reconstruction with anterior tracheal wall suspension in a patient with DiGeorge Syndrome. AB - DiGeorge Syndrome (DGS) may be associated with airway abnormalities including laryngomalacia and suprastomal collapse of the trachea (SCT), which may lead to sleep disordered breathing (SDB). We present a 4-year-old boy with DGS, SCT, and SDB by polysomnography (PSG) while the tracheostomy tube was capped. The patient underwent anterior tracheal wall suspension (ATWS) with concurrent tracheostomy decannulation. Following the repair, the patient experienced improved airway patency visually and by PSG with resolution of obstructive sleep apnea and hypoventilation. ATWS is an effective method to repair SCT in selected patients and may lead to early decannulation and improvement of SDB. PMID- 25129844 TI - Adaptations to local environments in modern human populations. AB - After leaving sub-Saharan Africa around 50000-100000 years ago, anatomically modern humans have quickly occupied extremely diverse environments. Human populations were exposed to further environmental changes resulting from cultural innovations, such as the spread of farming, which gave rise to new selective pressures related to pathogen exposures and dietary shifts. In addition to changing the frequency of individual adaptive alleles, natural selection may also shape the overall genetic architecture of adaptive traits. Here, we review recent advances in understanding the genetic architecture of adaptive human phenotypes based on insights from the studies of lactase persistence, skin pigmentation and high-altitude adaptation. These adaptations evolved in parallel in multiple human populations, providing a chance to investigate independent realizations of the evolutionary process. We suggest that the outcome of adaptive evolution is often highly variable even under similar selective pressures. Finally, we highlight a growing need for detecting adaptations that did not follow the classical sweep model and for incorporating new sources of genetic evidence such as information from ancient DNA. PMID- 25129848 TI - A new method of real-time skin dose visualization. Clinical evaluation of fluoroscopically guided interventions. AB - INTRODUCTION: We have conducted a prospective study to clinically evaluate a new radiation dose observing tool that displays patient's peak skin dose (PSD) map in real time. METHODS: The skin dose map (SDM) prototype quantifies the air kerma based on exposure parameters from the X-ray system. The accuracy of this prototype was evaluated with radiochromic films, which were used as a mean for PSD measurement. RESULTS: The SDM is a reliable tool that provides an accurate PSD estimation and location. CONCLUSION: SDM also has many advantages over the radiochromic films, such as real-time dose evaluation and easy access to critical operational parameters for physicians and technicians. PMID- 25129847 TI - Acute airway obstruction by Ascaris lumbricoides in a 14-month-old boy. AB - We describe the case of a 14-month-old child with airway obstruction caused by a mature Ascaris lumbricoides worm. The child had been admitted to the paediatric intensive care unit due to overwhelming sepsis, and during the course of his illness developed acute airway obstruction that resolved once the worm was removed from the airway. The Ascaris life-cycle is detailed, and a literature review of patients with airway obstruction due to Ascaris worms is presented. PMID- 25129849 TI - Severe depressive symptoms are associated with elevated endothelin-1 in younger patients with acute coronary syndrome. AB - OBJECTIVE: To explore the relationship of depressive symptom severity to circulating endothelin (ET)-1 in younger patients with acute coronary syndrome (ACS). Younger patients report greater depressive symptom severity, which predicts poorer post-ACS prognosis. The pathways linking depression to post-ACS prognosis require further elucidation. ET-1 is a potent endogenous vasoconstrictor which has been previously linked to adverse post-ACS outcomes. METHODS: The sample (n=153) included males <= 50 years of age and females <= 55 years of age who participated in a larger study. Blood samples for ET-1 assessment were collected within 2-3h of ACS admission. Depressive symptoms were assessed with the Beck Depression Inventory (BDI) II within 2-5 days of admission. ET-1 was treated as a transformed continuous variable (ET-1T). BDI-II scores were classified into four categories using conventional thresholds demarcating mild, moderate, and severe levels of depressive symptoms. The relationship of classified BDI-II score to ET-1T was examined in simple and multivariable linear regression models. RESULTS: Classified BDI-II score was related to ET-1T in both unadjusted (chi(2)=9.469, p=0.024) and multivariable (chi(2)=8.430, p=0.038) models, with ET-1T being significantly higher in patients with severe depressive symptoms than in those with mild and moderate depressive symptoms. CONCLUSIONS: In this sample of younger post-ACS patients, severe depressive symptoms were associated with elevated ET-1. We acknowledge that the observed association could be eliminated by the inclusion of some unmeasured variable(s). Longitudinal research should examine whether ET-1 mediates the relationship of depressive symptoms to long-term post-ACS outcomes. PMID- 25129850 TI - Optimism measured pre-operatively is associated with reduced pain intensity and physical symptom reporting after coronary artery bypass graft surgery. AB - OBJECTIVE: Optimism is thought to be associated with long-term favourable outcomes for patients undergoing coronary artery bypass graft (CABG) surgery. Our objective was to examine the association between optimism and post-operative pain and physical symptoms in CABG patients. METHODS: We assessed optimism pre operatively in 197 adults undergoing CABG surgery, and then followed them up 6-8 weeks after the procedure to measure affective pain, pain intensity, and physical symptom reporting directly pertaining to CABG surgery. RESULTS: Greater optimism measured pre-operatively was significantly associated with lower pain intensity (beta=-0.150, CI=-0.196 to -0.004, p=.042) and fewer physical symptoms following surgery (beta=-0.287, CI=-0.537 to -0.036, p=.025), but not with affective pain, after controlling for demographic, clinical and behavioural covariates, including negative affectivity. CONCLUSIONS: Optimism is a modest, yet significant, predictor of pain intensity and physical symptom reporting after CABG surgery. Having positive expectations may promote better recovery. PMID- 25129852 TI - Efficacy and safety of fronto-temporal transcranial random noise stimulation (tRNS) in drug-free patients with schizophrenia: a case study. PMID- 25129851 TI - Pithomyces species (Montagnulaceae) from clinical specimens: identification and antifungal susceptibility profiles. AB - The fungal genus Pithomyces comprises numerous dematiaceous saprobic species commonly found on dead leaves and stems of a great variety of plants. Occasionally, they have been recovered from clinical specimens. We morphologically and molecularly (rDNA sequences) investigated a set of 42 isolates tentatively identified as Pithomyces recovered from clinical specimens in the United States. The predominant species were P. chartarum and P. sacchari (33.3% each), followed by Pithomyces sp. I (28.6%) and P. maydicus (4.8%). Most of the isolates were obtained from samples of superficial tissue (50%), the respiratory tract (21.4%), and the nasal region (19%). In general, these fungi were highly susceptible in vitro to the eight antifungal agents tested. PMID- 25129853 TI - Mere extension of the field of resection cannot be the answer to surgery for metastatic spread: we need individualized approaches based on modern imaging techniques. PMID- 25129855 TI - Medical and molecular perspectives into a forgotten epidemic: encephalitis lethargica, viruses, and high-throughput sequencing. AB - The emergence of encephalitis lethargica (EL), an acute-onset polioencephalitis of unknown etiology as an epidemic in the years 1917-1925 is still unexplainable today. Questioned by the first descriptor of EL himself, Constantin von Economo, there has been much debate shrouding a possible role of the "Spanish" H1N1 influenza A pandemic virus in the development of EL. Previous molecular studies employing conventional PCR for the detection of influenza A virus RNA in archived human brain samples from patients who died of acute EL were negative. However, the clinical and laboratory characteristics of EL and its epidemiology are consistent with an infectious disease, and recently a possible enterovirus cause was investigated. With the rapid development of high-throughput sequencing, new information about a possible viral etiology can be obtained if sufficient specimens for analysis were still available today. Here, we discuss the implications of these technologies for the investigation of a possible infectious cause of EL from archived material, as well as a prospectus for future work for acquiring viral nucleic acids from these sources. PMID- 25129856 TI - A psoas abscess caused by Propionibacterium propionicum. AB - Pelvic actinomycosis-like disease due to Propionibacterium propionicum has been very rare and only a few cases have been reported in the literature. We herein report a probable first case of a psoas abscess caused by P. propionicum. Since P. propionicum is indistinguishable from Actinomyces israelii by morphological features or routine biochemical tests, 16S rRNA gene sequencing was useful to discriminate these two species in this case. PMID- 25129854 TI - Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. AB - BACKGROUND: Extracellular microRNAs (miRNAs) embedded in circulating exosomes may serves as prognostic biomarkers in cancer. OBJECTIVE: To identify and evaluate plasma exosomal miRNAs for prognosis in castration-resistant prostate cancer (CRPC). DESIGN, SETTING, AND PARTICIPANTS: RNA sequencing was performed to identify candidate exosomal miRNAs associated with overall survival in a screening cohort of 23 CRPC patients. Candidate miRNAs were further evaluated for prognosis using quantitative real-time polymerase chain reaction in a follow-up cohort of 100 CRPC patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox regression and Kaplan-Meier survival analyses were used to evaluate survival association using candidate miRNAs along with clinical prognostic factors. RESULTS AND LIMITATIONS: RNA sequencing in screening cohort generated approximately 6.80 million mappable reads per patient. Of those with normalized read counts >= 5, 43% were mapped to miRNAs for a total of 375 known and 57 novel miRNAs. Cox regression analysis identified an association of miR-1290, -1246, and -375 with overall survival (false discover rate < 0.05). Of those, higher levels of miR-1290 and -375 were significantly associated with poor overall survival (p < 0.004) in the follow-up cohort. Incorporation of miR-1290/-375 into putative clinical prognostic factors-based models in CRPC stage significantly improved predictive performance with a time-dependent area under the curve increase from 0.66 to 0.73 (p = 6.57 * 10(-6)). CONCLUSIONS: Plasma exosomal miR-1290 and miR 375 are promising prognostic biomarkers for CRPC patients. Prospective validation is needed for further evaluation of these candidate miRNAs. PATIENT SUMMARY: In this study, we evaluated whether small RNAs circulating in blood could be used to predict clinical outcomes in late-stage prostate cancer patients. We identified two blood-based small RNAs whose levels showed significant association with survival. Our results warrant further investigation because the noninvasive blood based test has great potential in the management of late-stage prostate cancer. PMID- 25129857 TI - Urethral polyp-like lesions on prostatic urethra caused by Chlamydia trachomatis infection: a case report. AB - Urethral polyp is one of differential diagnoses for the male patients complain of gross-hematuria and/or hematospermia. However, there have been limited numbers of case reports including infectious etiology. Here we reported clinical course and pathological findings of one rare case who was diagnosed and treated as urethral polyp-like lesions on the prostatic urethra caused by Chlamydia trachomatis infection. A 25 year-old man who had a past history of frequent sexual intercourse with unspecified female sexual partner visited the clinic. His chief complaint was gross-hematuria and hematospermia. Endoscopic findings showed that non-specific hemorrhagic polyp-like lesions. To determine the pathological findings including malignant diseases and diagnosis, transurethral resection was performed. Because the pathological findings were similar to those of chlamydial proctitis, additional examination was done. As the results, nucleic acid amplification test of C. trachomatis in urine specimen was positive and immunohistochemical staining of specific chlamydia antigen in resected specimen was also positive. Treatment by orally minocyline 100 mg twice daily for 4 weeks was introduced. After the treatment, symptom was disappeared and nucleic acid amplification test of C. trachomatis in urine specimen turned to be negative. No recurrence was reported 2 years posttreatment. PMID- 25129858 TI - Normalization of nano-sized TiO2-induced clastogenicity, genotoxicity and mutagenicity by chlorophyllin administration in mice brain, liver, and bone marrow cells. AB - The intensive uses of titanium dioxide (TiO2) nanoparticles in sunscreens, toothpaste, sweats, medications, etc. making humans exposed to it daily by not little amounts and also increased its risks including genotoxicity. Thus, the present study was designed as one way to reduce nano-titanium-induced clastogenicity, genotoxicity, and mutagenicity in mice by co-administration of the free radical scavenger chlorophyllin (CHL). In addition, markers of oxidative stress were detected to shed more light on mechanism(s) underlying nano-sized TiO2 genotoxicity. Male mice were exposed to multiple injection into the abdominal cavity for five consecutive days with either CHL (40 mg/kg bw/day), or each of three dose levels of nano-sized TiO2 (500, 1000, or 2000 mg/kg bw/day) alone, or both simultaneously and sacrificed by cervical dislocation 24 h after the last treatment. After CHL co-administration, the observed dose-dependent genotoxicity of TiO2 nanoparticles indicated by the significant elevations in frequencies of both micronuclei and DNA damage induction was significantly decreased and returned to the negative control level. The observed induced mutations in p53 exons 5, 7, & 8 and 5 & 8 in the liver and brain, respectively, were declined in most cases. Moreover, CHL significantly decreased hepatic malondialdehyde level and significantly increased glutathione level and superoxide dismutase, catalase, and glutathione peroxidase activities that were significantly disrupted in animal groups treated with nano-TiO2 alone. In conclusion, the evidenced in vivo genotoxicity of nano-TiO2 in the present study was normalized after CHL co-administration which supports the previously suggested oxidative stress as the possible mechanism for titanium toxicity. PMID- 25129859 TI - Remarkable diversity of tick or mammalian-associated Borreliae in the metropolitan San Francisco Bay Area, California. AB - The diversity of Lyme disease (LD) and relapsing fever (RF)-group spirochetes in the metropolitan San Francisco Bay area in northern California is poorly understood. We tested Ixodes pacificus, I. spinipalpis, and small mammals for presence of borreliae in Alameda County in the eastern portion of San Francisco Bay between 2009 and 2012. Analyses of 218 Borrelia burgdorferi sensu lato (Bb sl) culture or DNA isolates recovered from host-seeking I. pacificus ticks revealed that the human pathogen Bb sensu stricto (hereinafter, B. burgdorferi) had the broadest habitat distribution followed by B. bissettii. Three other North American Bb sl spirochetes, B. americana, B. californiensis and B. genomospecies 2, also were detected at lower prevalence. OspC genotyping of the resultant 167 B. burgdorferi isolates revealed six ospC alleles (A, D, E3, F, H and K) in I. pacificus. A novel spirochete belonging to the Eurasian Bb sl complex, designated CA690, was found in a questing I. spinipalpis nymph. Borrelia miyamotoi, a relapsing-fever (RF) group spirochete recently implicated as a human pathogen, was detected in 24 I. pacificus. Three rodent species were infected with Bb sl: the fox squirrel (Sciurus niger) with B. burgdorferi, and the dusky-footed wood rat (Neotoma fuscipes) and roof rat (Rattus rattus) with B. bissettii. Another spirochete that clustered phylogenetically with the Spanish R57 Borrelia sp. in a clade distinct from both the LD and RF groups infected some of the roof rats. Together, eight borrelial genospecies were detected in ticks or small mammals from a single Californian county, two of which were related phylogenetically to European spirochetes. PMID- 25129860 TI - Distinct Anaplasma phagocytophilum genotypes associated with Ixodes trianguliceps ticks and rodents in Central Europe. AB - Rodents are important reservoir hosts of tick-borne pathogens. Anaplasma phagocytophilum is the causative agent of granulocytic anaplasmosis of both medical and veterinary importance. In Europe, this pathogen is primarily transmitted by the Ixodes ricinus tick among a wide range of vertebrate hosts. However, to what degree A. phagocytophilum exhibits host specificity and vector association is poorly understood. To assess the extent of vector association of this pathogen and to clarify its ecology in Central Europe we have analyzed and compared the genetic variability of A. phagocytophilum strains from questing and feeding I. ricinus and Ixodes trianguliceps ticks, as well as from rodent' tissue samples. Tick collection and rodent trapping were performed during a 2-year study (2011-2012) in ecologically contrasting setting at four sites in Eastern Slovakia. Genetic variability of this pathogen was studied from the collected samples by DNA amplification and sequencing of four loci followed by Bayesian phylogenetic analyses. A. phagocytophilum was detected in questing I. ricinus ticks (0.7%) from all studied sites and in host feeding I. trianguliceps ticks (15.2%), as well as in rodent biopsies (ear - 1.6%, spleen - 2.2%), whereas A. phagocytophilum was not detected in rodents from those sites where I. trianguliceps ticks were absent. Moreover, Bayesian phylogenetic analyses have shown the presence of two distinct clades, and tree topologies were concordant for all four investigated loci. Importantly, the first clade contained A. phagocytophilum genotypes from questing I. ricinus and feeding I. ricinus from a broad array of hosts (i.e.,: humans, ungulates, birds and dogs). The second clade comprised solely genotypes found in rodents and feeding I. trianguliceps. In this study we have confirmed that A. phagocytophilum strains display specific host and vector associations also in Central Europe similarly to A. phagocytophilum' molecular ecology in United Kingdom. This study suggests that A. phagocytophilum genotypes associated with rodents are probably transmitted solely by I. trianguliceps ticks, thus implying that rodent-associated A. phagocytophilum strains may not pose a risk for humans. PMID- 25129861 TI - Dynamic loading of electrospun yarns guides mesenchymal stem cells towards a tendon lineage. AB - Alternative strategies are required when autograft tissue is not sufficient or available to reconstruct damaged tendons. Electrospun fibre yarns could provide such an alternative. This study investigates the seeding of human mesenchymal stem cells (hMSC) on electrospun yarns and their response when subjected to dynamic tensile loading. Cell seeded yarns sustained 3600 cycles per day for 21 days. Loaded yarns demonstrated a thickened cell layer around the scaffold's exterior compared to statically cultured yarns, which would suggest an increased rate of cell proliferation and/or matrix deposition, whilst maintaining a predominant uniaxial cell orientation. Tensile properties of cell-seeded yarns increased with time compared to acellular yarns. Loaded scaffolds demonstrated an up-regulation in several key tendon genes, including collagen Type I. This study demonstrates the support of hMSCs on electrospun yarns and their differentiation towards a tendon lineage when mechanically stimulated. PMID- 25129862 TI - Ligamentum teres injury is associated with the articular damage pattern in patients with femoroacetabular impingement. AB - PURPOSE: The objective of this study was to investigate the association between ligamentum teres injury and the hip joint cartilage damage pattern in patients with femoroacetabular impingement. METHODS: We compared articular cartilage damage between ligamentum teres-intact and-ruptured hips. Data were collected for 77 consecutive patients with femoroacetabular impingement who underwent hip arthroscopy. The locations of the chondral lesions were recorded on anatomic articular maps using the geographic zone method. The patients were divided into 2 groups (ligamentum teres-intact and-injured groups), and the incidence and degree of cartilage injury were compared between the 2 groups by use of the Mann-Whitney U test. RESULTS: In patients with ligamentum teres injury, chondral damage extended to the middle-inferior area of the acetabulum (7.6% [grade 1] in ligamentum teres-intact group and 66.6% [grade 1, 12.1%; grade 2, 42.4%; grade 3, 12.1%] in ligamentum teres-injured group, P < .01) and the apex of the femoral head (anterior apex: 7.1% [grade 1, 3.8%; grade 2, 3.3%] in intact group and 42.4% [grade 1, 30.3%; grade 2, 12.1%] in injured group, P < .01; middle apex: 7.6% [grade 1, 3.8%; grade 2, 3.8%] in intact group and 63.5% [grade 1, 42.4%; grade 2, 18.1%; grade 3, 3.0%] in injured group, P = .04; posterior apex: 7.6% [grade 1, 3.8%; grade 2, 3.8%] in intact group and 42.4% [grade 1, 30.3%; grade 2, 12.1%] in injured group, P < .01). CONCLUSIONS: This study showed the association between ligamentum teres injury and articular cartilage damage in the inferior middle part of the acetabulum and the apex of the femoral head in patients treated for femoroacetabular impingement. LEVEL OF EVIDENCE: Level IV, case-control study. PMID- 25129863 TI - Effects of varying locations for biceps tendon tenotomy and superior labral integrity on shoulder stability in a cadaveric concavity-compression model. AB - PURPOSE: The purpose of this study was to examine the location of biceps tenotomy and the integrity of the superior labrum as they relate to superior glenohumeral joint stability in a cadaveric concavity-compression model. METHODS: Eight cadaveric glenoid labrums were mounted individually onto a load cell with the corresponding humerus fixed to the loading arm in the hanging-arm position. All surrounding soft tissue was removed except the labrum and proximal stump of the long head of the biceps (LHB) tendon, simulating a biceps tenotomy. A compressive load of 22 N was applied across the glenohumeral joint. The humerus was then translated superiorly until it subluxated over the glenoid labrum. The force resisting superior translation was characterized for each of 50 cycles. Each specimen was tested under the following conditions: (1) with a 4 cm biceps stump after tenotomy, (2) with a 0 cm biceps stump, (3) after full detachment of the superior labrum, and (4) after repair of the labrum. RESULTS: Biceps tenotomy performed at the biceps-labral junction resulted in an average decrease in force required to superiorly subluxate the humeral head by 8.6% (P = .01) when compared with leaving 4 cm of biceps stump. Resection of the entire superior labrum resulted in a future decrease to 15.2% (P < .001) from baseline. Repair of the labrum resulted in restoration of stability with a mean of 101.1% (P = .82) and was not statistically different from baseline. The kinematics of the glenohumeral joint was affected by labral repair, with an earlier upslope on the force-to displacement curve and alteration in the total energy required to cause subluxation of the humeral head noted. CONCLUSIONS: In this study, location of the biceps tenotomy and integrity of the superior labrum affected glenohumeral stability during axial loading in the hanging-arm position. Repair of the labrum restored stability for superior subluxation but also changed the kinematics of the subluxation event. CLINICAL RELEVANCE: Preservation of superior labrum after biceps tenotomy provides increased resistive force to superior translation in a unidirectional biomechanical model. PMID- 25129864 TI - Preliminary development of a clinical prediction rule for treatment of patients with suspected SLAP tears. AB - PURPOSE: To use the clinical prediction rule process to identify patient variables, measured on initial clinical presentation, that would be predictive of failure to achieve satisfactory improvement, while following a rehabilitation program, in the modification of SLAP injury symptoms and dysfunction. METHODS: A cohort of patients received the clinical diagnosis of a SLAP lesion based on specific history and examination findings and/or magnetic resonance imaging. They underwent a physical examination of the kinetic chain and shoulder, including tests for labral injury. Patients followed a standardized physical therapy program emphasizing restoration of demonstrated strength, flexibility, and strength-balance deficits. At 6 weeks' follow-up, patients were re-evaluated and divided into those recommended for surgery (RS) and those not recommended for surgery (NRS). Bivariate logistic regression was performed to identify the best combination of predictive factors. RESULTS: Fifty-eight patients (aged 39 +/- 11 years, 45 men) were included. Of these, 31 (53%) were categorized as NRS and 27 (47%) as RS. The presence of a painful arc of motion (odds ratio, 3.95; P = .024) and the presence of increased forward scapular posture (odds ratio, 1.27; P = .094) on the injured side were predictive of being in the RS group. This finding indicates that the odds of being in the RS group increased 4 times when a positive painful arc was present and increased 27% with every 1-cm increase in involved anterior shoulder posture. CONCLUSIONS: A structured rehabilitation program resulted in modification of symptoms and improved function at 6 weeks' follow-up in over half of patients in the study group. On initial evaluation, the presence of a painful arc of overhead motion, indicating loss of normal glenohumeral kinematics, and the presence of forward shoulder posture, indicating an altered scapular position, represent negative predictive factors for success of rehabilitation. Future validation of the model in a larger population is necessary. LEVEL OF EVIDENCE: Level II, prospective comparative study. PMID- 25129865 TI - The role of arthroscopy in the management of glenohumeral osteoarthritis: a Markov decision model. AB - PURPOSE: The purposes of this study were (1) to construct a theoretical Markov decision model to compare the total remaining quality-adjusted life-years following either arthroscopic management (AM) or total shoulder arthroplasty (TSA) for the treatment of glenohumeral osteoarthritis and (2) to determine the possible effects of age on the preferred treatment strategy. METHODS: A Markov decision model was constructed to compare AM and TSA in patients with glenohumeral osteoarthritis. The rates of surgical complications, revision surgery, and death were derived from the literature and analyzed. The principal outcome measure was the mean total remaining quality-adjusted life-years after each treatment strategy. Sensitivity analyses were performed for age at the initial procedure, utilities, and transition probabilities. RESULTS: This theoretical decision model showed that AM was the preferred strategy for patients younger than 47 years, TSA was the preferred strategy for patients older than 66 years, and both treatment strategies were reasonable for patients aged between 47 and 66 years. The model was highly sensitive to age at the index surgery, utilities of wellness states, survivorship, and the probability of failure after either AM or TSA. CONCLUSIONS: According to this theoretical decision model, AM was the preferred treatment strategy for patients younger than 47 years, primary TSA was the preferred treatment strategy for patients older than 66 years, and both treatment options were reasonable for patients aged between 47 and 66 years. LEVEL OF EVIDENCE: Level II, economic and decision analysis. PMID- 25129866 TI - Gait and lower extremity kinematic analysis as an outcome measure after femoroacetabular impingement surgery. AB - PURPOSE: Lower extremity and pelvis kinematics have been shown to be abnormal in patients with femoroacetabular impingement (FAI). We conducted this systematic review to evaluate the current status of gait and lower extremity kinematics as an outcome measure in patients treated surgically for FAI. METHODS: We searched the Embase, Medline, and PubMed databases for all reports of studies published through February 22, 2014, evaluating kinematic assessment of patients undergoing FAI surgery. A review of eligible studies was conducted, and the references were searched. Methodologic quality was evaluated for all studies that met the inclusion and exclusion criteria, and data were extracted regarding methods of kinematic assessment and clinical and kinematic outcomes. RESULTS: We identified 633 reports, of which 5 met our eligibility criteria. These studies included a total of 58 patients with symptomatic FAI (age range, 18 to 50 years). All included studies were of moderate methodologic quality. Kinematic assessments were completed preoperatively and postoperatively with variable methodology and follow-up (range, 3 to 32 months). Most studies used high-speed motion-capture camera systems with reflective tracking markers to evaluate in vivo kinematic function. Of the 5 included studies, 3 documented kinematic improvements postoperatively particularly regarding sagittal hip range of motion primarily with flexion (weighted mean, 35.1 degrees +/- 5.4 degrees preoperatively and 37.8 degrees +/- 6.3 degrees postoperatively). CONCLUSIONS: Gait and lower extremity kinematics can be used as an outcome measure after FAI surgery. However, the lack of uniformity in the methodology used and underpowered case series limit the ability to identify clear and predictable differences after corrective surgery for FAI. Though statistically significant, functional outcome improvements were often conflicting and not necessarily of clinical significance. A uniform outcome measure and technique to reliably assess in vivo hip motion are required for future comparative studies. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies. PMID- 25129867 TI - Synthesis of heteroaryl/aryl kojic acid conjugates as stimulators of glucose uptake by GLUT4 translocation. AB - Insulin exerts its metabolic actions through the insulin receptor (IR) and plays an essential role in treatment of diabetes. The inconvenience of daily injections and the undesirable side-effects associated with insulin injections demand novel drugs for the disease. To search for bioactive insulin mimetic, we synthesized a chemical library of small molecules (2a-3f) based on the indolylkojic acid scaffold (B). An In vitro screening assay was performed to stimulate glucose transport in rat L6 skeletal muscle cells, post treatment of the compounds (2a 3f) for the time period incubation of 16 h. Compounds 2f, 2g, 2l, 3a, 3b, 3c and 3d have shown significant glucose uptake stimulation as compared to the controls at micromolar concentrations. In mechanistic studies, we observed that these compounds exert their biological action by enhancing GLUT4 translocation to cell surface via PI3K-dependent signalling pathway in agreement to the insulin mode of action. Hence, these promising conjugates should be useful for further drug development in diabetes treatment. PMID- 25129868 TI - Sequential synthesis of amino-1,4-naphthoquinone-appended triazoles and triazole chromene hybrids and their antimycobacterial evaluation. AB - A general method for the synthesis of a library of hitherto unreported amino-1,4 naphthoquinone-appended triazoles was accomplished via a sequential three component reaction of substituted N-propargylaminonaphthoquinones with variously substituted alkyl bromides/2-bromonaphthalene-1,4-dione and sodium azide in the presence of Et3N/CuI in water. Aminonaphthoquinone-appended iminochromene triazole hybrid heterocycles were also synthesized from the amino-1,4 naphthoquinone-appended-1,2,3-triazolylacetonitriles. All the triazole hybrids were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB). Among the triazoles, 2-(((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)(4 (trifluoromethyl)phenyl)amino)naphthalene-1,4-dione (7d) emerged as the most active one with IC50 = 1.87 MUM, being more potent than the anti-TB drugs, cycloserine (6 times), pyrimethamine (20 times) and equipotent as the drug ethambutol (IC50 < 1.56 MUM). PMID- 25129869 TI - Capsaicin cough threshold test in diagnostics. AB - BACKGROUND: Among patients with chronic unexplained cough, there is a recognized subgroup with respiratory symptoms induced by environmental irritants like chemicals and odours. The diagnosis of sensory hyperreactivity (SHR) has been suggested for this group of patients and can be made using a tidal breathing capsaicin inhalation test. The aim of the present study was to evaluate the ability of a single-breath, dose-response capsaicin threshold test to discriminate such patients from control subjects. METHODS: A total of 46 patients with chronic cough and SHR who had previously shown a positive reaction in accordance with limits set for a tidal breathing capsaicin test were tested once with a single-breath, dose-response capsaicin cough threshold test, assessing capsaicin concentrations to evoke 2 (C2), 5 (C5) or 10 (C10) coughs. Twenty-nine subjectively healthy control subjects were also included and tested with the threshold method. RESULTS: Patients had significantly lower C2, C5 and C10 in comparison to controls. From the results among patients and controls, sensitivity and specificity were calculated, and a receiver operating characteristic curve was constructed, showing excellent ability for C5 and C10 to discriminate patients from control subjects. CONCLUSIONS: For patients with SHR and chronic cough, capsaicin cough sensitivity was once again confirmed to be increased, in this case, using the single-breath dose-response method. Limits set for cough reactions regarded as more sensitive than normal can be useful in diagnostics and further research. C5 seems to be the best measure to use in research and differential diagnostics. PMID- 25129870 TI - Expression of adiponectin and adiponectin receptors 1 and 2 in the porcine uterus, conceptus, and trophoblast during early pregnancy. AB - Adiponectin, one of the several adipocytokines secreted mainly by the adipose tissue, plays an important role in regulating energy homeostasis and controls female fertility. Female reproductive functions are closely associated with nutritional status, and adiponectin seems to be an important factor linking the regulation of metabolic homeostasis with reproductive processes. The biological activity of adiponectin is mediated by two distinct receptors, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). The objective of this study was to determine the presence of and changes in the gene and protein expression pattern of adiponectin and its receptors in the porcine uterus during early pregnancy and on Days 10 to 11 of the estrous cycle and in the conceptus and trophoblast. The highest level of adiponectin transcript was observed on Days 15 to 16 of gestation, Days 10 to 11 of the cycle in the endometrium, and Days 15 to 16 of gestation in the myometrium. The highest expression of AdipoR1 and AdipoR2 genes was detected on Days 10 to 11 of gestation in the endometrium, and Days 12 to 13 in the myometrium. The highest content of adiponectin protein was noted on Days 12 to 13 and 30 to 32 of gestation in the endometrium and Days 10 to 11 of the cycle in the myometrium. The expression of adiponectin protein was higher on Days 27 to 28 and 30 to 32 in the conceptuses. AdipoR1 protein content in the myometrium was highest on Days 12 to 13 and 30 to 32. In contrast, in the endometrium, it was more constant. The highest content of AdipoR2 protein was detected on Days 15 to 16 and 30 to 32 of gestation, Days 10 to 11 of the cycle in the endometrium, and Days 10 to 11 of gestation in the myometrium. In the conceptuses, the highest AdipoR1 protein content was observed on Days 15 to 16, and the highest AdipoR2 protein expression was determined on Days 15 to 16 and 27 to 28. In the trophoblasts, AdipoR1 protein content was higher on Days 27 to 28 than on Days 30 to 32, whereas the expression of AdipoR2 was higher on Days 30 to 32. This study demonstrated the presence of adiponectin and its receptors in the uteri, conceptuses, and trophoblasts of pregnant pigs and that the local adiponectin system is dependent on the stage of pregnancy. PMID- 25129871 TI - Hydroxyflutamide alters the characteristics of live boar spermatozoa. AB - Our previous study revealed that in vitro incubation of boar ejaculates with hydroxyflutamide (OH-Flu) causes changes in sperm plasma membrane integrity and its stability and sperm mitochondrial oxidative capability. To broaden the knowledge of cellular physiology of spermatozoa, we investigated direct effects of OH-Flu administered for 2 and 24 hours at concentrations of 5, 50, and 100 MUg/mL, on sperm mitochondrial membrane potential and mitochondrial superoxide anion production using JC-1 dye and MitoSOX Red fluorescent probe, respectively. We further measured phosphatidylserine membrane translocation (PST) from the inner to the outer layer of the sperm plasma membrane using an annexin-V binding assay. To provide new information of direct effects of OH-Flu on cell signaling pathway, we measured sperm intracellular calcium ion dynamics using Fluo-3. Finally, we assessed sperm motility using a computer-assisted spermatozoa analysis system. Motile sperm were highlighted using the "C-Ruch" computer program for detailed analysis of the straight line velocity distribution. For each functional test, boar spermatozoa were examined and analyzed by flow cytometry and/or confocal microscopy. The results revealed a significant decrease (P<0.05) in sperm mitochondrial membrane potential and a concomitant increase (P<0.05) in mitochondrial superoxide anion production after a 2-hour incubation with 50 MUg OH-Flu compared with the respective controls and other doses used (P<0.05). The adverse effects of OH-Flu become strengthened over time (P<0.05). Notably, 50 and 100 MUg OH-Flu appeared to be effective in decreasing sperm motility. Hydroxyflutamide significantly decreased (P<0.05) the fast sperm subpopulation percentage after 15 minutes and reduced the straight line velocity distribution (P<0.05). An assessment of PST revealed an increase in the percentage of PST-positive spermatozoa (P<0.05) only after exposure to OH-Flu for 24 hours. Moreover, OH-Flu at all concentrations induced a rapid increase in sperm intracellular calcium ion concentration. Altogether, the altered in vitro characteristics of live boar spermatozoa provide new insight into direct effects of OH-Flu on sperm mitochondrial membrane potential, superoxide anion production, translocation of membrane phosphatidylserine, free calcium ion dynamics, and sperm motility. PMID- 25129872 TI - DNA fragmentation and sperm head morphometry in cat epididymal spermatozoa. AB - Sperm DNA fragmentation is an important parameter to assess sperm quality and can be a putative fertility predictor. Because the sperm head consists almost entirely of DNA, subtle differences in sperm head morphometry might be related to DNA status. Several techniques are available to analyze sperm DNA fragmentation, but they are labor-intensive and require expensive instrumentations. Recently, a kit (Sperm-Halomax) based on the sperm chromatin dispersion test and developed for spermatozoa of different species, but not for cat spermatozoa, became commercially available. The first aim of the present study was to verify the suitability of Sperm-Halomax assay, specifically developed for canine semen, for the evaluation of DNA fragmentation of epididymal cat spermatozoa. For this purpose, DNA fragmentation indexes (DFIs) obtained with Sperm-Halomax and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) were compared. The second aim was to investigate whether a correlation between DNA status, sperm head morphology, and morphometry assessed by computer-assisted semen analysis exists in cat epididymal spermatozoa. No differences were observed in DFIs obtained with Sperm-Halomax and TUNEL. This result indicates that Sperm Halomax assay provides a reliable evaluation of DNA fragmentation of epididymal feline spermatozoa. The DFI seems to be independent from all the measured variables of sperm head morphology and morphometry. Thus, the evaluation of the DNA status of spermatozoa could effectively contribute to the completion of the standard analysis of fresh or frozen semen used in assisted reproductive technologies. PMID- 25129873 TI - Neuroimaging findings in primary insomnia. AB - State-of-the-art neuroimaging techniques have accelerated progress in the study and understanding of sleep in humans. Neuroimaging studies in primary insomnia remain relatively few, considering the important prevalence of this disorder in the general population. This review examines the contribution of functional and structural neuroimaging to our current understanding of primary insomnia. Functional studies during sleep provided support for the hyperarousal theory of insomnia. Functional neuroimaging also revealed abnormalities in cognitive and emotional processing in primary insomnia. Results from structural studies suggest neuroanatomical alterations in primary insomnia, mostly in the hippocampus, anterior cingulate cortex and orbitofrontal cortex. However, these results are not well replicated across studies. A few magnetic resonance spectroscopy studies revealed abnormalities in neurotransmitter concentrations and bioenergetics in primary insomnia. The inconsistencies among neuroimaging findings on insomnia are likely due to clinical heterogeneity, differences in imaging and overall diversity of techniques and designs employed. Larger samples, replication, as well as innovative methodologies are necessary for the progression of this perplexing, yet promising area of research. PMID- 25129874 TI - Emotional maltreatment and disordered eating in adolescents: testing the mediating role of emotion regulation. AB - The present study aimed to determine if emotion regulation mediates the relationship between emotional maltreatment and disordered eating behavior in adolescents. Participants were 222 secondary school pupils (aged 14-18 years) from a state high school in the UK. Standardized questionnaire measures were used to gather self-report data on emotional abuse and emotional neglect, functional and dysfunctional emotion regulation strategies and disordered eating behavior. Results showed that disordered eating was associated with emotional abuse, dysfunctional emotion regulation and being female. Multiple mediation analysis found an indirect relationship between emotional abuse and disordered eating through dysfunctional emotion regulation. Interestingly, emotional neglect predicted lower levels of functional emotion regulation. The findings support previous research showing emotion regulation to mediate the relationship between childhood abuse and disordered eating in adults and a differential effect of abuse and neglect on emotion regulation. Longitudinal studies are required to confirm the direction of relationships; however these data suggest that dysfunctional emotion regulation is a significant variable in the development of disordered eating and may be a useful target for intervention. PMID- 25129875 TI - Cadmium concentrations and their implications in Mallard and Coot from fish pond areas. AB - During the studies in 2003, high concentrations of cadmium (Cd) were noted among Mallards and Coots in Poland. Further research, five years later, showed the histopathological alterations in birds from the same area which were probably stimulated by Cd. This paper presents the analysis of Cd in ten different materials collected from these species (n=180) in years 2006-2009 in two areas, including southern - Zator and western Poland - Milicz. Similarly high concentrations to those from 2003 were noted only in kidneys of Mallards from the Zator area (up to 56.49 MUg g(-1) d.w.). Other comparable materials accumulated significantly lower concentration of Cd. Generally, lower concentrations occurred in birds from Milicz. Concentrations varied also between species and age groups. They correlated between liver and kidneys, brain and muscle and brain and spleen. Potential in vivo bioindicators (blood, feathers and excrements) did not seem to be useful as biomarkers in both areas. PMID- 25129876 TI - Comparison of accuracy of two different methods to determine ankle-brachial index to predict peripheral arterial disease severity confirmed by angiography. AB - Ankle-brachial index (ABI) is conventionally derived as the ratio of higher of the 2 systolic ankle blood pressures to the higher brachial pressure (HABI method). Alternatively, ABI may be derived using the lower of the 2 systolic ankle pressures (LABI method). The objective of this study was to assess the utility and difference between 2 techniques in predicting peripheral artery disease (PAD). Participants who underwent both ABI measurement and arteriography from July 2005 to June 2010 were reviewed. Angiographic disease burden was scored semiquantitatively (0=<50%, 1=50% to 75%, and 2=>75% stenosis of any lower extremity arterial segment), and PAD by angiography was defined as >50% stenosis of any 1 lower extremity arterial segment. A combined PAD disease score was calculated for each leg. A total of 130 patients were enrolled (260 limbs). The ABI was <0.9 (abnormal) in 68% of patients by HABI method and in 84% by LABI. LABI method had higher sensitivity and overall accuracy to detect PAD compared with the HABI method. Regression analysis showed that an abnormal ABI detected by LABI method is more likely to predict angiographic PAD and total PAD burden compared with HABI. Moreover, abnormal ABI by LABI method had higher sensitivity and accuracy to detect PAD in patients with diabetes and below knee PAD compared with the HABI method. In conclusion, ABI determined by the LABI method has higher sensitivity and is a better predictor of PAD compared with the conventional (HABI) method. PMID- 25129877 TI - Alcohol consumption and risk of death in male physicians with heart failure. AB - The 5-year risk of death after onset of heart failure (HF) is about 50%. Although previous studies have shown beneficial effects of light-to-moderate alcohol consumption and risk of cardiovascular diseases and mortality, it is unclear whether moderate alcohol consumption is associated with a lower risk of death in subjects with HF. We investigated whether alcohol consumption and type of alcohol preference are associated with the risk of total mortality in 449 US male physicians with prevalent HF. Alcohol consumption was assessed through food frequency questionnaire, and mortality was ascertained through annual follow-up questionnaires and adjudicated by an Endpoint Committee. The mean age of subjects was 75.7+/-8.2 years with an average follow-up of 7 years. We found evidence of a J-shaped relation between alcohol consumption and mortality (hazard ratio [95% confidence interval] 1.00 [reference], 0.85 [0.61 to 1.20], 0.60 [0.40 to 0.88], and 0.71 [0.42 to 1.21] for alcohol intake of none, <1 drink/day, 1 to 2 drinks/day, and 3+ drinks/day, respectively [p for quadratic trend=0.058]). There was no relation between beverage preference (beer, wine, or liquor) and mortality. In conclusion, our data showed a J-shaped association between alcohol intake and mortality in patients with HF. PMID- 25129878 TI - Subclinical myocardial injury identified by cardiac infarction/injury score and the risk of mortality in men and women free of cardiovascular disease. AB - Previous studies have explored the ability of the Cardiac Infarction/Injury Score (CIIS) to identify individuals who are high risk for cardiovascular disease (CVD) mortality. However, its prognostic significance among those without CVD in the United States general population has not been established. This analysis included 6,298 participants (mean age 59+/-13 years, 53% women, 51% nonwhites) from the Third National Health and Nutrition Examination Survey, excluding participants with a history of CVD or electrocardiographic evidence of old myocardial infarction or ischemic ST depression at baseline. Subclinical myocardial injury was defined as CIIS>=10. Mortality data were ascertained using the National Death Index. Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between subclinical myocardial injury and CVD and all-cause mortalities. Subclinical myocardial injury was detected in 1,376 participants (22%). A total of 1,928 deaths occurred during a median follow-up of 14 years of which 765 (40%) were due to CVD. In a multivariate model adjusted for demographics, traditional CVD risk factors, and other medical co-morbidities, subclinical myocardial injury was associated with an increased risk of CVD (HR 1.26, 95% CI 1.02 to 1.56) and all cause (HR 1.42, 95% CI 1.23 to 1.63) mortalities. In conclusion, subclinical myocardial injury in those without manifestations of CVD is associated with an increased risk of CVD and all-cause mortalities. These findings highlight the important role of CIIS to identify subclinical myocardial injury and its association with mortality among men and women in the United States. PMID- 25129879 TI - Determination of organophosphorus pesticides in stomach contents of postmortem animals by QuEChERS and gas chromatography. AB - The quick, easy, cheap, effective, rugged and safe (QuEChERS) method for sample preparation was applied to determine seven organophosphorus pesticides (OPs) in stomach contents of poisoned postmortem animals. The pesticides consisted of diazinon, edifenphos, ethyl p-nitrophenyl phenylphosphonothioate, fenitrothion, monocrotophos, parathion and phosphamindon, and tested samples included stomach contents from postmortem animals of cattle, goat, dog, cat, birds, deer and rabbit. The pesticides were spiked into the samples which were found to be negative through previous pesticide poisoning analysis, and the pesticides were extracted and cleaned up based on the QuEChERS process and then they were analyzed using gas chromatography (GC)-flame photometric detector (FPD) or GC nitrogen-phosphorus detector (NPD) with a DB-5 column. Limits of detection ranged from 0.27 to 0.41 mg/kg for the seven pesticides. The mean recoveries ranged from 80 to 99% in GC-FPD and 83 to 90% in GC-NPD. The coefficients of variation were <10% for all analytes and sample matrix combinations except for phosphamidon and edifenphos in dog stomach contents. This study demonstrated that the method using QuEChERS and GC-FPD and/or GC-NPD is very effective to analyze the OPs in the stomach contents of postmortem animals. PMID- 25129880 TI - Cardiac autonomic responses induced by mental tasks and the influence of musical auditory stimulation. AB - We investigated the acute effects of musical auditory stimulation on cardiac autonomic responses to a mental task in 28 healthy men (18-22 years old). In the control protocol (no music), the volunteers remained at seated rest for 10 min and the test was applied for five minutes. After the end of test the subjects remained seated for five more minutes. In the music protocol, the volunteers remained at seated rest for 10 min, then were exposed to music for 10 min; the test was then applied over five minutes, and the subjects remained seated for five more minutes after the test. In the control and music protocols the time domain and frequency domain indices of heart rate variability remained unchanged before, during and after the test. We found that musical auditory stimulation with baroque music did not influence cardiac autonomic responses to the mental task. PMID- 25129881 TI - Additional effects of homeopathy on chronic periodontitis: a 1-year follow-up randomized clinical trial. AB - BACKGROUND AND OBJECTIVE: The aim of this study was test the hypothesis that homeopathy (H) enhances the effects of scaling and root planing (SRP) in patients with chronic periodontitis (CP). MATERIALS AND METHODS: 50 patients with CP were randomly allocated to one of two treatment groups: SRP (C-G) or SRP + H (H-G). Assessments were made at baseline and after 3 and 12 months of treatments. The local and systemic responses to the treatments were evaluated by clinical and serologic parameters, respectively. RESULTS: Both groups displayed significant improvements, however, using clinical attachment gain and reductions in HDL, LDL and Total Cholesterol, Triglycerides, Glucose and Uric acid, from baseline to 1 year, as criteria for treatment success, H-G performed significantly better than C-G. CONCLUSION: The findings of this 1-year follow-up randomized clinical trial suggest that homeopathic medicines, as an adjunctive to SRP, can provide significant local and systemic improvements for CP patients. PMID- 25129882 TI - The effects of family-friend visits on anxiety, physiological indices and well being of MI patients admitted to a coronary care unit. AB - OBJECTIVE: To investigate the effect of family-friend visits on anxiety, physiological indices and well-being of patients with acute myocardial infarction. METHODS: A checklist was used to gather socio-demographic data and physiologic indices including blood pressure, heart rate, respiratory rate, and arterial oxygen saturation. The short-form of the Spielberger state anxiety inventory, a visual analog scale well-being and cardiac monitoring devices were used for collecting data. RESULTS: Patients exhibited a lower heart rate and respiratory rate in the normal range during the 10-min visiting period and within 10 and 30 min after the visiting period. The arterial oxygen saturation increased in this period. After the visiting period, patients exhibited an increase in the sense of well-being and a decrease in the level of anxiety. CONCLUSION: Family friend visits can improve MI patients' sense of well-being and decrease their anxiety. Moreover, the visits can help to keep the physiological indices within normal limits. PMID- 25129884 TI - Effect of Rosa damascene aromatherapy on sleep quality in cardiac patients: a randomized controlled trial. AB - OBJECTIVE: Sleep disorders are common among patients hospitalized in coronary care unit (CCU). This study aimed to investigate the effect of Rosa damascene aromatherapy on sleep quality of patients hospitalized in CCU. METHODS: In this randomized controlled trial, 60 patients who met the inclusion criteria were conveniently sampled and randomly allocated to the experimental and control groups. Patients in the control group received routine care. In the experimental group, patients received routine care and Rosa damascene aromatherapy for three subsequent nights. In the both groups the sleep quality was assessed using the Pittsburgh Sleep Quality Index. RESULTS: After the study, the mean scores of five domains of Pittsburg Sleep Quality Index as well as the mean of total score of the index in the experimental group were significantly lower than the control group. CONCLUSION: Rosa damascene aromatherapy can significantly improve the sleep quality of patients hospitalized in CCUs. PMID- 25129885 TI - Report on a membership audit of the Association of Chartered Physiotherapists in Reflex Therapy (ACPIRT). AB - Reflex Therapy (RT), akin to reflexology, is a non-invasive physiotherapy modality approved by the UK Chartered Society of Physiotherapists. One hundred members of the Association of Chartered Physiotherapists in Reflex Therapy (ACPIRT) participated in an audit to establish a baseline of practice. Findings indicate that experienced therapists use RT in conjunction with their professional skills to induce relaxation (95%) and reduce pain (86%) for patients with conditions including whiplash injury and chronic pain. According to 68% of respondents, RT is "very good," "good" or "as good as" orthodox physiotherapy practices. Requiring minimal equipment, RT may be as cost effective as orthodox physiotherapy with regards to duration and frequency of treatment. PMID- 25129883 TI - Trauma-sensitive yoga as an adjunct mental health treatment in group therapy for survivors of domestic violence: a feasibility study. AB - This study is a feasibility test of whether incorporating trauma-sensitive yoga into group therapy for female victims of partner violence improves symptoms of anxiety, depression, and posttraumatic stress disorder (PTSD) beyond that achieved with group therapy alone. Seventeen (9 control, 8 intervention) adult female clients seeking group psychotherapy were enrolled. A 12-week trauma sensitive yoga protocol was administered once weekly for 30-40 min at the end of each group therapy session. The control group received typical group psychotherapy. Feasibility was assessed through recruitment and retention rates as well as participants' self-reported perceptions of the safety and utility of the study. The study enrolled 85% (17/20) of those screened eligible. Loss to follow-up was 30% (5/17). No one reported emotional or physical harm. All of the respondents reported that the study was personally meaningful and that the results would be useful to others. PMID- 25129886 TI - Reprogramming the genetic code in vitro. AB - The site-specific introduction of non-canonical amino acids into polypeptides through genetic code reprogramming has become a powerful tool for biochemical studies and bioorganic synthesis. Although a variety of such techniques have been developed, all are based on the 'mis-acylation' of tRNA molecules with non canonical amino acids. Multiple strategies have been devised to synthesize such non-canonical aminoacyl-tRNAs; for example, those based on protein or ribozyme aminoacyl-tRNA synthetase enzymes are particularly useful. Such techniques have enabled the incorporation of hundreds of different non-canonical amino acids into polypeptides in vitro. This review discusses the development and application of in vitro genetic code reprogramming techniques, especially enzymatic mis acylation, and examines recent efforts to engineer the translational machinery to increase the range of translatable non-canonical amino acids. PMID- 25129888 TI - Disgust as a unique affective predictor of mental contamination following sexual trauma. AB - Mental contamination has been described as an internal experience of dirtiness that can arise and persist in the absence of contact with observable physical contaminants. Recent research has examined mental contamination specifically related to unwanted physical contact and sexual trauma. This study evaluated the degree to which disgust propensity and both self-focused and perpetrator-focused peritraumatic disgust were associated with mental contamination in a sample of women who experienced sexual trauma (n=72). Results showed that peritraumatic self-focused disgust, but not peritraumatic perpetrator-focused disgust or fear, was significantly associated with mental contamination. Additionally, disgust propensity contributed significantly to the incremental validity of the model. These findings support the nascent literature showing that disgust plays a significant role in mental contamination, particularly following sexual trauma. Future research directions, and clinical/theoretical implications of these results are discussed. PMID- 25129889 TI - The Cortical Signature of Central Poststroke Pain: Gray Matter Decreases in Somatosensory, Insular, and Prefrontal Cortices. AB - It has been proposed that cortical structural plasticity plays a crucial role in the emergence and maintenance of chronic pain. Various distinct pain syndromes have accordingly been linked to specific patterns of decreases in regional gray matter volume (GMV). However, it is not known whether central poststroke pain (CPSP) is also associated with cortical structural plasticity. To determine this, we employed T1-weighted magnetic resonance imaging at 3 T and voxel-based morphometry in 45 patients suffering from chronic subcortical sensory stroke with (n = 23) and without CPSP (n = 22), and healthy matched controls (n = 31). CPSP patients showed decreases in GMV in comparison to healthy controls, involving secondary somatosensory cortex (S2), anterior as well as posterior insular cortex, ventrolateral prefrontal and orbitofrontal cortex, temporal cortex, and nucleus accumbens. Comparing CPSP patients to nonpain patients revealed a similar but more restricted pattern of atrophy comprising S2, ventrolateral prefrontal and temporal cortex. Additionally, GMV in the ventromedial prefrontal cortex negatively correlated to pain intensity ratings. This shows for the first time that CPSP is accompanied by a unique pattern of widespread structural plasticity, which involves the sensory-discriminative areas of insular/somatosensory cortex, but also expands into prefrontal cortex and ventral striatum, where emotional aspects of pain are processed. PMID- 25129890 TI - Factors contributing to home-based acceptability of rapid testing for HIV infection among the inner city commuter population in Johannesburg, South Africa. AB - BACKGROUND: The study aimed to determine factors contributing to the acceptability of home-based HIV counselling and testing (HBHCT) among commuters in Johannesburg inner city. METHODS: Simple random sampling was used to select participants in a venue based intercept survey at Noord Street taxi rank in Johannesburg central business district. A total of 1146 individuals were interviewed and logistic regression analysis assessed factors associated with HBHCT acceptability. RESULTS: HBHCT acceptability was 64%. Home testing was preferred as an alternative to testing at a health facility. High school education (adjusted odds ratio [aOR] 0.61, CI: 0.46-0.85), inner city residence aOR 0.70, CI: 0.52-0.94), previous HIV testing in the hospital (aOR 0.22, CI: 0.15-0.32) and at home (aOR 0.18, CI: 0.11-0.27) were significantly less likely associated with HBHCT acceptability. Being married (aOR 1.64, CI: 1.15-2.32), recent HIV testing (aOR 1.85, CI: 1.15-2.99) and having experienced negative health worker attitude (aOR 2.41, CI: 1.66-3.48) were significantly more likely associated with HBHCT acceptability. CONCLUSIONS: High acceptability of HBHCT among urban-based commuters plus factors that would deter HBHCT acceptability were identified. Further research to identify strategies to improve HBHCT acceptability among commuter populations is needed. PMID- 25129891 TI - Childhood mortality and its association with household wealth in rural and semi urban Burkina Faso. AB - BACKGROUND: This study aimed to investigate the relationship between household wealth and under-5 year mortality in rural and semi-urban Burkina Faso. METHODS: The study included 15 543 children born between 2005 and 2010 in the Nouna Health and Demographic Surveillance System. Information on household wealth was collected in 2009. Two separate wealth indicators were calculated by principal components analysis for the rural and the semi-urban households, which were then divided into quintiles accordingly. Multivariable Cox proportional hazards regression was used to study the effect of the respective wealth measure on under 5 mortality. RESULTS: We observed 1201 childhood deaths, corresponding to 5-year survival probability of 93.6% and 88% in the semi-urban and rural area, respectively. In the semi-urban area, household wealth was significantly related to under-5 mortality after adjustment for confounding. There was a similar but non-significant effect of household wealth on infant mortality, too. There was no effect of household wealth on under-5 mortality in rural children. CONCLUSIONS: Results from this study indicate that the more privileged children from the semi urban area with access to piped water and electricity have an advantage in under 5 survival, while under-5 mortality in the rural area is rather homogeneous and still relatively high. PMID- 25129892 TI - Prediction of postoperative atrial fibrillation after cardiac surgery: light at the end of the tunnel? PMID- 25129893 TI - Phenylephrine in cardiac surgery: will it have a place? PMID- 25129894 TI - Authors' reply: How much evidence is the evidence for a case report? PMID- 25129887 TI - Absence of a simple code: how transcription factors read the genome. AB - Transcription factors (TFs) influence cell fate by interpreting the regulatory DNA within a genome. TFs recognize DNA in a specific manner; the mechanisms underlying this specificity have been identified for many TFs based on 3D structures of protein-DNA complexes. More recently, structural views have been complemented with data from high-throughput in vitro and in vivo explorations of the DNA-binding preferences of many TFs. Together, these approaches have greatly expanded our understanding of TF-DNA interactions. However, the mechanisms by which TFs select in vivo binding sites and alter gene expression remain unclear. Recent work has highlighted the many variables that influence TF-DNA binding, while demonstrating that a biophysical understanding of these many factors will be central to understanding TF function. PMID- 25129895 TI - Authors' reply. PMID- 25129896 TI - US court invalidates Pfizer's Celebrex(r) patent. PMID- 25129897 TI - Idenix files three patent infringement lawsuits in Europe. PMID- 25129898 TI - Iroko pharmaeuticals announces patent for ZorvolexTM. PMID- 25129899 TI - The evolution of the rubber endotracheal tube. PMID- 25129900 TI - Jeanette Thirlwell: three decades of service to the Journal. PMID- 25129901 TI - Education and training in ultrasound-guided neuraxial anaesthesia. PMID- 25129902 TI - Screening for colorectal cancer and prostate cancer: challenges for New Zealand. Richardson and Potter's reply. PMID- 25129903 TI - Without rewards, the cycle of innovation would stop. PMID- 25129904 TI - Charging what the market will bear is inappropriate. PMID- 25129905 TI - Greater effectiveness for the same cost. PMID- 25129906 TI - The system over-rewards incremental gains. PMID- 25129907 TI - Impressive gains with innovative medicines. PMID- 25129908 TI - Waste and missed opportunities drive costs upward. PMID- 25129909 TI - Short-term costs can lead to long-term gain. PMID- 25129910 TI - Eliminate cost-plus reimbursement for drugs. PMID- 25129911 TI - [No methodological data? No comparable laboratory results]. PMID- 25129912 TI - [New antibiotics with activity against multidrug-resistant enterobacteriaceae. Combination preparations are now being tested clinically]. PMID- 25129913 TI - [Point of care analyses are not used uniformly in primary health care. Equalis survey shows that volume and the type of tests performed varies between different health care centers]. PMID- 25129914 TI - [Swedish cooperation for genomic analyses of breast cancer tissue. Basis for future individualized cancer treatment]. PMID- 25129915 TI - [Register studies measure the effectiveness of drugs in clinical practice. The example PsoReg - redistribution of systemic treatment can increase the efficiency]. PMID- 25129917 TI - [Freeze-dried plasma should be available for use in Swedish health care]. PMID- 25129916 TI - [Bleeding and surgery in the treatment with new oral anticoagulants. The management can be complicated by the lack of specific antidotes]. PMID- 25129918 TI - [The GUCH example: A challenge to educate future "super specialists"]. PMID- 25129919 TI - ["There is no educational culture of in health care"]. PMID- 25129920 TI - [Statistical analysis improves medicine history research]. PMID- 25129921 TI - [Woody plant species composition and community structure in residual fragments of broad-leaved Korean pine mixed forests in Changbai Mountains area]. AB - The broad-leaved Korean pine mixed forest represents the typical vegetation type of the eastern mountain area in Northeast China. However, due to the interference of human activities, the natural broad-leaved Korean pine forest only distributes in some residual fragments with unequal areas in Changbai Mountains and Small Hinggan Mountains. To compare and analyze the similarities and differences of broad-leaved Korean pine mixed forests in the different areas, we established six forest plots following the field protocol of the 50 hm2 forest plot in Panama (Barro Colorado Island, BCI) in 2012 in Changbai Mountain National Nature Reserve in Jilin Province and the eastern mountain area in Liaoning Province. All free standing plant species with DBH (diameter at breast height) > or = 1 cm were mapped, tagged and identified to species. The results showed that there were 69 woody species in the six plots, comprising 42 genera and24 families. Aceraceae was the most species-rich family in all six plots. Most species belonged to the plant type of North Temperate Zone, with a minor subtropical plant species component. The statistics of species abundance, basal area, mean DBH, and importance value showed that there were obviously dominant species in each community. The DBH distribution of all individuals showed a reversed "J" type. However, the percentage of individuals in small size-class and large size-class varied in the six communities, which indicated that these communities were at different successional stages. Ranked by the importance value, the DBH distribution of the top three species in the six plots showed four distribution types: reversed "J" distribution, reversed "L" distribution, unimodal distribution, and partial peak distribution. Spatial distribution patterns of the main species in the six plots changed differently with species and size-class, and the distribution patterns of the same species varied in the different plots. PMID- 25129922 TI - [Ecologically critical areas of broad-leaved Korean pine mixed forest in Changbai Mountains, China]. AB - In order to improve the protection system to reduce the damage of biodiversity and protect broad-leaved Korean pine mixed forest, 64 forest farms from 6 Forestry Bureaus around Changbai Mountains Nature Reserve were investigated and analyzed. A total of 41 plants were selected as key protected plants, and felling area, cropland, mining area, highway, railway and residential area were considered as the disturbance factors. GAP and GIS spatial analysis were used to draw the indicator plant and disturbance intensity distribution maps. The results showed that the indicator species distribution was uneven. The indicator plant enrichment regions were located on the north western and southern slopes centered with Shengli and Lenggouzi forest farms of Quanyang County, respectively, and single distributions of the endemic plants were found in Baoshan, Henshan, Lenggouzi and Heishan forest farms. The different disturbance severities were observed in the different forest farms, among which the north part in Lushuihe and Baihe forest farms were severely disrupted. Two ecologically critical areas, Quanyang-Lushuihe-Baihe on the north slope of Changbai Mountains and the east part of Changbai County on the south slope, were determined based on the comprehensive analysis. PMID- 25129923 TI - [Variation of forest vegetation carbon storage and carbon sequestration rate in Liaoning Province, Northeast China]. AB - The forest vegetation carbon stock and carbon sequestration rate in Liaoning Province, Northeast China, were predicted by using Canadian carbon balance model (CBM-CFS3) combining with the forest resource data. The future spatio-temporal distribution and trends of vegetation carbon storage, carbon density and carbon sequestration rate were projected, based on the two scenarios, i. e. with or without afforestation. The result suggested that the total forest vegetation carbon storage and carbon density in Liaoning Province in 2005 were 133.94 Tg and 25.08 t x hm(-2), respectively. The vegetation carbon storage in Quercus was the biggest, while in Robinia pseudoacacia was the least. Both Larix olgensis and broad-leaved forests had higher vegetation carbon densities than others, and the vegetation carbon densities of Pinus tabuliformis, Quercus and Robinia pseudoacacia were close to each other. The spatial distribution of forest vegetation carbon density in Liaoning Province showed a decrease trend from east to west. In the eastern forest area, the future increase of vegetation carbon density would be smaller than those in the northern forest area, because most of the forests in the former part were matured or over matured, while most of the forests in the later part were young. Under the scenario of no afforestation, the future increment of total forest vegetation carbon stock in Liaoning Province would increase gradually, and the total carbon sequestration rate would decrease, while they would both increase significantly under the afforestation scenario. Therefore, afforestation plays an important role in increasing vegetation carbon storage, carbon density and carbon sequestration rate. PMID- 25129924 TI - [Estimating leaf area index of black locust (Robinia pseudoacacia L.) plantations based on texture parameters of quickbird imagery]. AB - The black locust plantations located in Weibei area were chosen as research objects and the texture parameters of different window sizes from high resolution imagery were measured. Four different techniques, including simple linear regression model, quadratic regression model, power model and exponential model, were developed to describe the relationship between the texture parameters and field measurements of LAI and to select the most effective texture parameters and window size. The results showed that the texture parameters influenced the accuracy of LAI estimation. Angular second moment and entropy index yielded better adjust r2 than the other parameters. The r2 changed with the window size. Dissimilarity and contrast index gained the largest r2 when the window size was 9x9. The r2 of the other texture parameters reduced as the window size increased and a window size of 3 x 3 was more successful than any of the others. Power equation performed poorest than the other three techniques for estimation of LAI. PMID- 25129925 TI - [Effects of simulated nitrogen deposition on growth and phosphorus efficiency of Pinus massoniana under low phosphorus stress]. AB - Atmospheric nitrogen (N) deposition dramatically raised in recent decades, resulting in increases of soil N availability and N/P ratio, which would impact plant growth and P efficiency under low P stress. Taking breeding population of Pinus massoniana as test materials, a pot experiment was conducted to simulate two P conditions, i. e., homogeneous low P availability vs. heterogeneous low P among soil layers, in combination with two N deposition levels on growth traits and P absorption and utilization efficiency of P. massoniana. Under the homogeneous low phosphorus condition, growth traits and P efficiency of P. massoniana were not significantly improved by simulated nitrogen deposition, but significant nitrogen x family interaction effect was detected, with the biomass of family 40x44 and 71x20 being increased, 36x29 and 73x23 being decreased. Under the heterogeneous low P condition, significant N effects on the seedling height, biomass and P absorption efficiency were observed, due to promoted root length and root distribution ratio of topsoil. In addition, the effects of simulated N deposition on growth and P efficiency of P. massoniana were relevant to the N/P ratio. Under the homogeneous low P condition, the N/P ratio of P. massoniana plant was 13.8, plants exhibited a low sensitivity to simulated N deposition, root secreted APase activity was increased but the plant growth was not promoted. In comparison, the plant N/P ratio was 9.7 under the heterogeneous low P condition, and the plant growth and P efficiency were significantly promoted, while no obvious change occurred in root secreted APase activity. PMID- 25129926 TI - [Changes in vegetation and soil characteristics under tourism disturbance in lakeside wetland of northwest Yunnan Plateau, Southwest China]. AB - The characteristics of vegetation and soil were investigated in Bita Lake and Shudu Lake wetlands in northwest Yunnan Plateau under tourism disturbance. The 22 typical plots in the wetlands were classified into 4 types by TWINSPAN, including primary wetland, light degradation, moderate degradation, and severe degradation. Along the degradation gradient, the plant community density, coverage, species number and Shannon diversity index increased and the plant height decreased in Bita Lake and Shudu Lake wetlands, and Whittaker diversity index increased in Bita Lake wetland. Plant species number, soil organic matter, total nitrogen, porosity, available nitrogen, available phosphorus and available potassium contents were higher in Shudu Lake wetland than in Bita Lake wetland, but the plant density, height, soil total potassium and pH were opposite. Canonical correspondence analysis (CCA) by importance values of 42 plants and 11 soil variables showed that soil organic matter, total nitrogen and total potassium were the key factors on plant species distribution in Bita Lake and Shudu Lake wetlands under tourism disturbance. TWINSPAN classification and analysis of vegetation-soil characteristics indicated the effects of tourism disturbance in Bita Lake wetland were larger than in Shudu Lake wetland. PMID- 25129927 TI - [Effects of snow pack on soil nitrogen transformation enzyme activities in a subalpine Abies faxioniana forest of western Sichuan, China]. AB - This study characterized the dynamics of the activities of urease, nitrate reductase and nitrite reductase in both soil organic layer and mineral soil layer under three depths of snow pack (deep snowpack, moderate snowpack and shallow snowpack) over the three critical periods (snow formed period, snow stable period, and snow melt period) in the subalpine Abies faxoniana forest of western Sichuan in the winter of 2012 and 2013. Throughout the winter, soil temperature under deep snowpack increased by 46.2% and 26.2%, respectively in comparison with moderate snowpack and shallow snowpack. In general, the three nitrogen-related soil enzyme activities under shallow snowpack were 0.8 to 3.9 times of those under deep snowpack during the winter. In the beginning and thawing periods of seasonal snow pack, shallow snowpack significantly increased the activities of urease, nitrate and nitrite reductase enzyme in both soil organic layer and mineral soil layer. Although the activities of the studied enzymes in soil organic layer and mineral soil layer were observed to be higher than those under deep- and moderate snowpacks in deep winter, no significant difference was found under the three snow packs. Meanwhile, the effects of snowpack on the activities of the measured enzymes were related with season, soil layer and enzyme type. Significant variations of the activities of nitrogen-related enzymes were found in three critical periods over the winter, and the three measured soil enzymes were significantly higher in organic layer than in mineral layer. In addition, the activities of the three measured soil enzymes were closely related with temperature and moisture in soils. In conclusion, the decrease of snow pack induced by winter warming might increase the activities of soil enzymes related with nitrogen transformation and further stimulate the process of wintertime nitrogen transformation in soils of the subalpine forest. PMID- 25129928 TI - [Effects of drought stress on growth and water use efficiency of two medicinal plants]. AB - Growth characteristics, stable carbon isotope discrimination (Delta13C), water use efficiency (WUE), and their correlation of Cassia obtusifolia and Isatis indigotica were measured at three soil water levels, i. e., 30%, 50% and 75% of field water holding capacity (FWHC), and at three growth stages. The growth indices of the two medicinal plants at 75% of FWHC were higher than those at 30% and 50% of FWHC, suggesting that the two medicinal plants could obtain high production under sufficient moisture condition. The Delta13C(A) (aboveground biomass-based Delta13C) and Delta13C(T) (total biomass-based Delta13C) decreased, and the WUE(A) (aboveground biomass-based WUE) and WUE(T) (total biomass-based WUE) of C. obtusifolia and I. indigotica increased with the increasing degree of drought stress. The growth indices of the two medicinal plants had little difference in the different water treatments, which indicated that the two medicinal plants were insensitive to drought stress. Water use efficiency of I. indigotica had significant negative relationships with aboveground biomass and total biomass, while that of C. obtusifolia had a significant positive correlation with the root/shoot ratio. PMID- 25129929 TI - [Effects of stand structure regulation on soil labile organic carbon in Pinus elliottii plantation]. AB - Taking 21-year-old Pinus elliottii pure plantation as the control, effects of enrichment planting with broadleaf trees (Liquidambar fornosana) after thinning the conifer trees (P. elliottii) on soil labile organic carbon of different plantations, including 3-year-old, 6-year-old, 9-year-old P. elliottii and 21 year-old P. elliottii-L. fornosana mixed plantations, were investigated. The results showed that the contents of soil dissolved organic carbon (DOC), readily oxidizable organic carbon (ROC), and microbial biomass carbon (MBC) significantly increased in the 6-year-old and 9-year-old plantations compared with those in the 21-year-old P. elliottii pure plantation. Soil labile organic carbon contents in the 21-year-old P. elliottii-L. fornosana mixed plantation increased significantly than those in 3-year-old, 6-year-old, 9-year-old stands, and the DOC, ROC and MBC contents increased by 113.1%, 53.3% and 54.6%, respectively, compared with those in the 21-year-old P. elliottii pure plantation. The results suggested that replanting with broadleaf trees are an effective measure to improve the soil ecological function in pure P. elliottii plantation. PMID- 25129930 TI - [Community structure and distribution of riparian Bambusa rigida along lower Gongjiang River, China]. AB - The community structure and distribution of secondary riparian Bambusa rigida in lower Gongjiang River were studied by the transect sampling method and reverse age-class addition. The species in tree and shrub layers in the riparian B. rigida community had the strong native trait. Along the river gradient, the associated species in tree and shrub layers were fragmented, and associated with shore highland plants, suggesting that their distribution did not meet the RCC theory of continuous riparian law. Plant species in herb layer was in accordance with the RCC law, and the species abundance in lower reach was the greatest with 29 families, 55 genera, and 70 species. B. rigida was absolutely dominant in the riparian communities and adapted to the regulation of tree density and physiological integration. The proliferation ratio of B. rigida rapidly decreased to become stabilized, and the degree of its clump dispersion pattern gradually increased. The average density of secondary riparian B. rigida was 114-141 bamboo trees per clump, and the community was in the mid- and late succession stage. PMID- 25129931 TI - [Root system distribution and biomechanical characteristics of Bambusa oldhami]. AB - To determine the mechanism of soil stabilizing through Bambusa oldhami root system, the vertical distribution of B. oldhami root system in soil was investigated, and the tensile strength of individual root and soil shear strength were measured in B. oldhami forest. The dry mass, length, surface area and volume of the B. oldhami root system decreased with the increasing soil depth, with more than 90% of the root system occurring in the 0-40 cm soil layer. The root class with D 1 mm occupied the highest percentage of the total in terms of root length, accounting for 79.6%, but the lowest percentage of the total in terms of root volume, accounting for 8.2%. The root class with D >2 mm was the opposite, and the root class with D= 1-2 mm stayed in between. The maximum tensile resistance of B. oldhami root, either with 12% moisture content or a saturated moisture content, increased with the increasing root diameter, while the tensile strength decreased with the increasing root diameter in accordance with power function. Tensile strength of the root, with either of the two moisture contents, was significantly different among the diameter classes, with the highest tensile strength occurring in the root with D < or = 1 mm and the lowest in the root with D > or = 2 mm. The tensile strength of root with 12% moisture content was significantly higher than that with the saturated moisture content, and less effect of moisture content on root tensile strength would occur in thicker roots. The shear strengths of B. oldhami forest soil and of bare soil both increased with the increasing soil depth. The shear strength of B. oldhami forest soil had a linear positive correlation with the root content in soil, and was significantly higher than that of bare soil. The shear strength increment in B. oldhami forest was positively correlated with the root content in soil according to an exponential function, but not related significantly with soil depth. PMID- 25129932 TI - [Adaptability analysis of FAO Penman-Monteith model over typical underlying surfaces in the Sanjiang Plain, Northeast China]. AB - It is very important for studying surface energy and water balance to improve the accuracy of evapotranspiration (ET) estimation. Based on eddy covariance measurements and microclimate observational data available, comparisons were done in accuracy of simulating ET with the FAO Penman-Monteith model from the marshland, rice paddy and soybean field in the Sanjiang Plain. The results showed that the values of ET simulated with the model over marshland was significantly higher than the measured one (averagely 81.8% higher) when the crop coefficients recommend by FAO were adopted, and its modeling efficiency was negative, which indicated that the ET from the marshland couldn' t be simulated by the model. While the seasonal variation of ET over rice paddy and soybean field could be simulated by the model and the accuracy in simulating ET from rice paddy was better than that from soybean field. Crop coefficients (Kc) of marshland, rice paddy and soybean field were all significantly positively related to leaf area index, and crop coefficient of soybean field was also significantly negatively related to vapor pressure deficit. With Kc modified through linear regression, the FAO Penman-Monteith model markedly improved the estimation accuracy for marshland, rice paddy and soybean field, with the mean bias error ranging from 0.1 to 0.3 mm x d(-1), root mean square error ranging from 0.50 to 0.67 mm x d( 1) and modeling efficiency ranging from 0.69 to 0.85. Still, the accuracy in simulating ET from rice paddy was superior to that from the other two underlying surfaces. The FAO Penman-Monteith model was suitable to simulate the ET from rice paddy whether the crop coefficient was modified or not. However, the crop coefficient must be modified if the model was used to simulate the ET from marshland and soybean field. PMID- 25129933 TI - [Effects of irrigation amount on morphological characteristics and water use of Jatropha curcas]. AB - Jatropha curcas is the most promising energy tree, and soil moisture is the key factor which affects the seedling quality and water use efficiency of J. curcas. With aims to evaluate the effect of different irrigation amount on growth, morphological characteristics and water use of J. curcas, a pot experiment was conducted with four irrigation amounts, i. e., W1:472.49 mm, W2: 228.79 mm, W3:154.18 mm and W4:106.93 mm, respectively. Compared with W1 treatment, the leaf area and stem cross-section area of base significantly decreased in W2, W3 and W4 treatments, but Huber value significantly increased, which could improve the efficiency of water transfer from root to shoot, thus enhance the capability of resistance to drought stress. Compared with W, treatment, the healthy index of J. curcas seedlings decreased slightly in W2 treatment but significantly decreased in W3 and W4 treatments. Hence, the irrigation amount from 228.79 to 472.49 mm was beneficial to increase the healthy index of J. curcas seedlings. Compared with W1 treatment, irrigation water was saved by 67.4% in W3 treatment, and the total dry mass and evapotranspiration significantly decreased by 17.4% and 68.6%, and the irrigation water use efficiency and total water use efficiency increased by 153.2% and 163.2%, respectively. In the condition of this study, the irrigation amount of 154.18 mm was beneficial to increase water use efficiency. PMID- 25129934 TI - [Characteristics of soil organic carbon mineralization at different temperatures in paddy soils under long-term fertilization]. AB - Dynamics of soil organic carbon mineralization affected by long-term fertilizations and temperature in relation to different soil carbon fractions were investigated in paddy soils. Soil samples were collected from the plough layer of 3 long-term national experimental sites in Xinhua, Ningxiang and Taojiang counties of Hunan Province. Mineralization of soil organic C was estimated by 33-day aerobic incubation at different temperatures of 10, 20 and 30 degrees C. The results showed that the rates of CO2 production were higher during the earlier phase (0-13 d) in all treatments, and then decreased according to a logarithm function. Higher incubation temperature strengthened C mineralization in the different treatments. The quantities of cumulative CO2 production in NPK with manure or straw treatments were greater than in inorganic fertilizers treatments. The Q10 values in the different soil treatments ranged from 1.01 1.53. There were significantly positive correlations between the Q10 values and soil total organic carbon (TOC), easy oxidation organic carbon (EOOC), humic acid carbon (C(HA)), fulvic acid carbon (CFA). The cumulative amount of mineralized C was significantly positively correlated with microbial biomass carbon (MBC) at 10 and 20 degrees C, but not significantly at 30 degrees C. Significant correlations were found between the cumulative amount of mineralized C and different soil carbon fractions and C(HA)/C(FA). The correlations of differ- ent soil carbon fractions with the ratio of cumulative mineralized C to TOC were negatively correlated at 10 degrees C, but not significantly at 20 and 30 degrees C. These results suggested that the application of NPK with manure or straw would be helpful to increase the sequestration of C in paddy soils and reduce its contribution of CO2 release in the atmosphere. PMID- 25129935 TI - [Impacts of nighttime warming on rice growth stage and grain yield of leading varieties released in different periods in Jiangsu Province, China]. AB - A field experiment was conducted to investigate the actual impacts of nighttime warming on rice growth stage and grain yield in Danyang, Jiangsu Province, with 8 leading varieties approved and released during 1970s-2000s. The field was warmed at nighttime for an entire growth stage (i. e. sown date to harvest) with a Free Air Temperature Increase (FATI) facility. The results showed that there were significant differences in the extents of warming impact on rice growth stage and grain yield among the leading varieties, though the impact trends were similar. An increase of 0.9 degrees C in nighttime mean temperature in rice canopy could shorten the length of rice entire growth stage by 1.3 d. Nighttime warming tended to decrease post-anthesis green leaves area and the flag leaf area, and to decline rice aboveground biomass production and grain yield by 3.5% and 5.1%, respectively. Meanwhile, nighttime warming decreased the plant nitrogen concentration at maturity. Nighttime warming reduced the grain yield mainly through decreasing the effective panicles and grain numbers per panicle. There was no stable changing trend in the differences in warming impacts on the varieties released in the different periods. PMID- 25129936 TI - [Effects of all-day warming on growth, development and yield of winter wheat cultivars bred in different periods]. AB - A field experiment was conducted to study the effects of all-day warming on the growth, development and yield of winter wheat cultivars bred in different periods under free air temperature increase (FATI) in Xuzhou and Danyang, Jiangsu Province. Warming decreased the effective tillers by 5.2% and 9.6%, and the ineffective tillers by 15.6% and 9.7% in Xuzhou and Danyang, respectively. Plant height under FATI was higher in Xuzhou, but lower in Danyang than that of the control. Plant heights of the late cultivars were lower than that of the early cultivars. Warming increased the leaf area index for all cultivars. Warming increased the net photosynthetic rates of the winter wheat cultivars except for those bred in 1950-1960s and 1980s in Xuzhou and 1950-1960s and 1990s in Danyang. There were different changing tendencies of the night respiration rate among the winter wheat cultivars bred in different periods. Aboveground biomass and harvest index of all cultivars increased under FATI. Harvest index of late cultivars was higher than that of early cultivars in Xuzhou and Danyang. Growth period of different cultivars under FATI was all shortened, av- eragely by 3.2 and 4.1 d in Xuzhou and Danyang, respectively, mainly due to shortening the preheading stage (averagely by 7.5 and 8.5 d in Xuzhou and Danyang, respectively) and prolonging the filling stage (by average 4.3 d). Except for 1950-1960s cultivars in Xuzhou, the grain yields increased under FATI, averagely by 21.0% and 14.1% in Xuzhou and Danyang, respectively. Statistical analysis of variance showed that the warming induced wheat yield changes were due to the changes in grain number per spike and effective spikes in Xuzhou and the change in 1000-grain mass in Danyang, respectively. PMID- 25129937 TI - [Effects of N and S application on grain filling characteristics and yield of winter wheat]. AB - A field experiment was conducted on the Guanzhong Plain, China, to evaluate the effects of N and S application on characteristics of winter wheat (cv. Xiaoyan 22) grain filling and yield, using a central composite rotatable design with two factors nitrogen (N) and sulfur (S). The results showed that, with the combined application of N and S, grain filling followed a "S" curve which increased slowly at first, then quickly, and then slowly again. With 108 and 267 kg N x hm(-2), the grain fill duration, theoretical maximum grain yield, and average filling rate decreased as the S application rate increased. With 97.5 and 202.5 kg S x hm(-2), N application improved grain filling parameter values. With 187.5 kg N x hm(-2) or 150 kg S x hm(-2), the parameters firstly increased, reached a maximum, and then decreased as the S or N input increased. Grain filling rate increased for 25 days following anthesis, and then declined at a rate that varied among treatments. When the N input was > 187.5 kg x hm(-2) or the S input was > 150 kg x hm(-2), the grain filling rate decreased with increasing the S or N input. The results also indicated that combined application of N and S fertilizers at appropriate rates could increase the head density and grain yield. Using the regression equations, highest grain yields estimates (> or = 3753 kg x hm(-2)) were achieved with the combination of a high N rate (178.31-256.36 kg x hm(-2)) and a moderate S rate (131.95-167.65 kg x hm(-2)). PMID- 25129938 TI - [Effects of shading on endogenous hormones regulation in kernel development of summer maize in the field]. AB - Taking 3 maize hybrids, Zhenjie 2 (ZJ2), Denghai 605 (DH605) and Zhengdan 958 (ZD958) as test materials, the effects of shading on the physiological function of endogenous hormones during grain formation of summer maize were investigated in the field. The ambient sunshine treatment was used as the control (CK) and 3 shading treatments with a shading degree of 60% were designed in growth periods ranging from tasseling to maturity (S1), from jointing to tasseling stage (S2) and whole growing period (S3), respectively. Results showed that the total floret number, filament number and pollination floret number decreased after shading in comparison with CK, and aborted seeds increased accordingly. The kernels per ear showed an order of CK > S2 > S > S3, and those of S1, S2 and S3 were 18.9%, 43.7% and 80.8% lower than that of CK. The IAA, GA and ZR contents of normal grain in the shading treatments were lower than in CK, while the ABA content was opposite. The same hormone change with grain growth in all treatments presented a similar trend. Compared to normal grains, the maximum value of IAA content in aborted grains shifted from the 20th day to the 10th day after pollination, with less IAA accumulation and rapid reduction, and the contents of GA and ZR decreased significantly, while that of ABA was still high at the 20th day after pollination. Therefore, the effects of shading on hormone contents in grains might lead to grain abortion and yield reduction. PMID- 25129939 TI - [Effects of high temperature and humidity stress at the physiological maturity stage on seed vigor, main nutrients and coat structure of spring soybean]. AB - A pot experiment was conducted to investigate the effects of high temperature and humidity stress [(40 +/- 2) degrees C/(30 +/- 2) degrees C, RH (95 +/- 5)%/(70 +/ 5)%, 10 h/14 h (day/night)] at the physiological maturity stage of two spring soybean cultivars (Xiangdou No. 3 and Ningzhen No. 1) on seed vigor indices, main nutritional components and coat anatomical structure. High temperature and humidity stress were found to cause the decrease of seed viability, germination potential, and germination percentage as well as the dehydrogenase and acid phosphatase activities, but increased the seed cell membrane permeability as well as H+, soluble sugar and leucine levels in the seed soaking liquid of each cultivar. Moreover, the stress led to irregular changes of seed oil and protein contents and alteration of anatomical structure of episperm and hilum in the two cultivars. A shortterm stress (less than 5 h) had no significant impact on seed vigor, but a long-term one (more than 48 h) caused rapid decrease of seed vigor indices. Xiangdou No. 3 showed less decreases in seed germination potential and enzyme activities, and less increase in extravasation content in the seed soaking liquid, had compact seed coat and intact hilum, suggesting it was more resistant to high temperature and humidity stress. PMID- 25129940 TI - [Effects of root cutting under different seedling conditions on root system distribution and senescence character of peanut]. AB - The effects of root cutting on root system distribution and senescence character of peanut (Arachis hypogaea) under different seedling conditions were investigated by using the box culture method. The results showed that, with three types of peanut seedlings, including overgrowing, strong and week seedlings, root cutting all first restricted and then promoted the root system growth, especially promoted the root growth to deep soil. This effect was stronger on the overgrowing and strong seedlings, while relatively weaker on the weak seedlings. After root cutting, root activity, superoxide dismutase (SOD) and peroxidase (POD) activity all reduced at first, and then increased, compared with each control. The extents of decrease in root activity, SOD and POD activity were highest in the weak seedlings, lowest in the overgrowing seedlings, and moderate in the strong seedlings. However, in the later stage after root cutting, the extents of increase in root activity, SOD and POD activity were higher in the overgrowing and strong seedlings, than in the weak seedlings. Generally, root cutting could promote the root activity of peanut and delay the senescence. PMID- 25129941 TI - [Effects of exogenous silicon on physiological characteristics of cucumber seedlings under ammonium stress]. AB - The present study evaluated the effects of exogenous silicon on growth and physiological characteristics of hydroponically cultured cucumber seedlings under ammonium stress. The results showed that the growth, especially the aerial part growth of cucumber seedlings cultured with ammonium were significantly inhibited than those with nitrate, especially after treatment for 10 d, the aerial part fresh mass of cucumber seedlings were reduced 6.17 g per plant. The accumulation of reactive oxygen species (ROS) was also promoted in cucumber seedlings under ammonium, and the contents of O2*- and H2O2 were significantly increased in cucumber leaves. With the exogenous silicon treatment, the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) were significantly improved, the ability to remove reactive oxygen species was enhanced, the contents of O2*- and H2O2 were significantly reduced in cucumber leaves, decreasing the reactive oxygen damage to the cell membrane, and the ratio of electrolyte leakage and the content of MDA in cucumber leaves. Also, with exogenous silicon treatment, the plasma membrane and activity of vacuolar membrane H(+)-ATP was significantly increased, transport capacity of intracellular proton was improved, and the level of ammonium in cucumber body was significantly reduced, thereby reducing the toxicity of ammonium. In conclusion, exogenous silicon could relieve ammonium stress, by increasing the antioxidant enzyme activity, H(+)-ATP activity, and decreasing the ammonium content in cucumber seedlings. PMID- 25129942 TI - [Effects of nutrition medium on cucumber growth and soil microenvironment in greenhouse under continuous cropping]. AB - An experiment of continuous cropping of cucumber in nutrition medium (composted with straw, rural soil and puffed chicken manure) or soil was conducted in greenhouse in order to study the effects of medium type on the cucumber growth and soil microenvironment, respectively. The results showed that the two treatments both displayed different levels of obstacles resulted from continuous cropping. In the same cropping season, the nutrient content, soil invertase and urease activities and B/F (bacteria/fungi) ratio in the nutrition medium were obviously higher but fungi quantity was lower than in the soil medium, suggesting the use of nutrition medium changed the bacterial population structure as to improve the cucumber growth and yield. Under continuous cropping, correlation analysis showed that the bacterial quantity was significantly positively related with plant height and root dry mass, and markedly significantly positive correlation exited between the aboveground dry mass and yield of cucumber. The urease activity was also significantly positively related with the cucumber yield. Compared with the soil medium, the nutrition medium could greatly improve soil microenvironment and alleviate the continuous cropping obstacle. PMID- 25129943 TI - [Optimal nighttime temperature for tomato plant in greenhouse in autumn and winter]. AB - In order to investigate the effect of nighttime temperature (NT) on adult stage tomato plants in greenhouse, an experiment was conducted by using natural light growth chamber. Tomato plants were treated with 4 nighttime temperature as natural NT (CK), 14, 16, and 18 degrees C, on condition of the same daytime temperature (DT). Actual NT of CK, 14, 16, and 18 degrees C treatments were 13.1, 13.4, 14.7, and 16.3 degrees C, respectively. Physiological response, photosynthesis, dry matter accumulation and production of tomato plant under different NT treatments were determined. The results showed that, tomato plants under CK treatment suffered lower temperature press periodically, and the membrane system was damaged to some extent, resulting in the lowest dry matter accumulation and nearly no early yield (28 g mature fruit per plant). Compared with CK, dry matter accumulation of tomato plant under 14 degrees C treatment was increased significantly, early yield was 304 g per plant, and total production was increased by 58% (immature fruit included). As for the 18 degrees C treatment, the net photosynthetic rate (Pn) of tomato plant was significantly increased by 10.6%-12.5%, dry matter accumulation was increased by 26%, flower time was advanced by 4-12 days, fruit number per plant was 3.8, fresh matter per fruit was increased by 42.7 g, early yield per plant was 476 g, and the total production per plant was increased by 101%. All the items under 16 degrees C treatment were between those under 14 degrees C and 18 degrees C treatments. Therefore, at DT of 22 degrees C, the low NT limit was 13.4 degrees C and the optimal NT should be above 16.3 degrees C for greenhouse tomato plants in autumn and winter in North China. PMID- 25129944 TI - [Effect of shifting sand burial on evaporation reduction and salt restraint under saline water irrigation in extremely arid region]. AB - The Taklimakan Desert Highway Shelterbelt is drip-irrigated with high saline groundwater (2.58-29.70 g x L(-1)), and shifting sand burial and water-salt stress are most common and serious problems in this region. So it is of great importance to study the effect of shifting sand burial on soil moisture evaporation, salt accumulation and their distribution for water saving, salinity restraint, and suitable utilization of local land and water resources. In this study, Micro-Lysimeters (MLS) were used to investigate dynamics of soil moisture and salt under different thicknesses of sand burial (1, 2, 3, 4, and 5 cm), and field control experiments of drip-irrigation were also carried out to investigate soil moisture and salt distribution under different thicknesses of shifting sand burial (5, 10, 15, 20, 25, 30, 35, and 40 cm). The soil daily and cumulative evaporation decreased with the increase of sand burial thickness in MLS, cumulative evaporation decreased by 2.5%-13.7% compared with control. And evaporative inhibiting efficiency increased with sand burial thickness, evaporative inhibiting efficiency of 1-5 cm sand burial was 16.7%-79.0%. Final soil moisture content beneath the interface of sand burial increased with sand burial thickness, and it increased by 2.5%-13.7% than control. The topsoil EC of shifting sand in MLS decreased by 1.19-6.00 mS x cm(-1) with the increasing sand burial thickness, whereas soil salt content beneath the interface in MLS increased and amplitude of the topsoil salt content was higher than that of the subsoil. Under drip-irrigation with saline groundwater, average soil moisture beneath the interface of shifting sand burial increased by 0.4% -2.0% compare with control, and the highest value of EC was 7.77 mS x cm(-1) when the sand burial thickness was 10 cm. The trend of salt accumulation content at shifting sand surface increased firstly, and then decreased with the increasing sand burial thickness. Soil salt contents beneath the interface of shifting sand burial were much lower than that of shifting sand surface. 35 cm was the critical sand burial thickness for water-saving and salt restraint. In summary, sand burial had obvious inhibition effects on soil evaporation and salt accumulation, so maybe it could be used to save water and reduce salt accumulation in arid shifting desert areas. PMID- 25129945 TI - [Quantitative analysis of the built-up area expansion in Su-Xi-Chang region, China]. AB - Based on RS-derived maps and socio-economic statistics, this paper analyzed the spatiotemporal dynamic pattern and driving mechanism of built-up area expansion in Su-Xi-Chang region from 1990 to 2010. 3S-based spatial analysis techniques were used, landscape expansion indices were calculated, and multiple stepwise regression models were also used. In the past 20 years, the built-up area had experienced rapid-moderate-accelerating expansion stages, which was strongly affected by the national development strategies and policies regarding land use. During the study period, the built-up area had increased by 2218.9 km2 mainly due to the encroaching from paddy field, dryland and artificial ponds. From 1990 1995, the pattern of built-up area expansion was dominated by the infilling and edge-expansion type; from 1995-2000, the outlying-type had overplayed infilling and edge-expansion types due to policy restrictions on the latter; after 2000, the outlying-type growth had decreased by a large extent, whereas the infilling mode had increased dramatically, which resulted in the spatially compact pattern of the newly built-up area. The increase of urban population and the boom of regional economy were the major driving forces of built-up area expansion. The study implied that improvements were urgently needed in land management system and high-efficiency use of cropland. Promoting the compact development of built up area was also crucial for striving toward regional sustainability. PMID- 25129946 TI - [Evaluation of ecosystem service values of the forests of Shennongjia Nature Reserve]. AB - As an ecological protected area for rare animals and plants in a subtropical forest zone, Shennongjia National Reserve plays an important role in the study of biodiversity in China. By using the market value, shade-price and opportunity cost methods, the forest ecosystem service values of Shennongjia National Nature Reserve were evaluated, including forest production, recreation and culture, water conservation, soil conservation, gas regulation, environment purification, nutrient circulation and biodiversity conservation. The total value of the Shennongjia Nature Reserve was approximately 204.33 x 10(8) yuan RMB x a(-1). The values of the different functions were in order of biodiversity conservation (68.5%) > soil conservation (12.7%) > recreation and culture (4.9%) > gas regulation (4.8%) > forest production (4.2%) > water conservation (3.9%) > environment purification (0.7%) > nutrient circulation (0.3%). The values with respect to utility were in sequence of unused value (68.5%) > indirect value in use (22.4% ) > direct value in use (9.1%). PMID- 25129947 TI - [Responses of ecosystem services value to land use change in national nature reserves in Xinjiang, China]. AB - With GIS and RS technology, characteristics of land use change and ecosystem services value of different years in six national nature reserves in Xinjiang, China were analyzed with remote sensing image of the year 2000-2010. Results showed that the area of water body and grassland decreased while the area of forest, farmland, wetland, unused land and construction land increased in 2000 2010. Variation rate of land use change in 2000-2005 was faster, as 2.4-6.3 times as that in 2005-2010. The total ecosystem services value mostly consisted of that of water body, grassland and forest, accounting for 93% approximately. During the study, the values of all kinds of the ecosystem services increased except for grassland and water body, the total ecosystem services value increased firstly and then decreased, and overall emerged as a reducing trend with the rate of 1.2%. In the process of the development of the west regions, it is necessary to pay more attention to the protection of natural resources and ecosystem restoration, so as to achieve sustainable development of resources, environment and social economy in the western regions. PMID- 25129948 TI - [Evaluation of wetland ecological benefit and restoration in the natural reserves of western Jilin Province, China]. AB - In order to correctly evaluate wetland ecological benefit and restoration in the natural reserves of western Jilin Province, an index system of wetland ecological benefit assessment for nature reserves was established based on ecosystem service theory and catastrophe theory. Considering the diversity characteristics of ecological benefit, and consulting the research results of ecological benefit in study area in 2001, the analytic hierarchy process and entropy method were introduced to analyze the ecological benefit and restoration in 2005 and 2012. The results showed that the ecological benefit level was very high in Momoge Nature Reserve since 2005, high in Chaganhu and Xianghai nature reserves, and moderate in Dabusu Nature Reserve. This study showed that the assessment combining the catastrophe progression method with the analytic hierarchy process and entropy method could reveal the dynamics and the integrality of wetland ecological benefit, and accurately reflect the reality of the ecological restoration in study area. In recent years, some achievements in ecological protection and environmental remediation had been obtained in the west of Jilin Province, and the whole ecological benefit of the wetlands had been improved and enhanced by means of man-made effective interference. PMID- 25129949 TI - [System construction of early warning for ecological security at cultural and natural heritage mixed sites and its application: a case study of Wuyishan Scenery District]. AB - This paper proposed a new concept of ecological security for protection by a comprehensive analysis of the contents and standards of world heritage sites. A frame concept model named "Pressure-State-Control" for early warning of ecological security at world heritage mixed sites was constructed and evaluation indicators of this frame were also selected. Wuyishan Scenery District was chosen for a case study, which has been severely disturbed by natural and artificial factors. Based on the frame model of "Pressure-State-Control" and by employing extension analysis, the matter-element model was established to assess the ecological security status of this cultural and natural world heritage mixed site. The results showed that the accuracy of ecological security early warning reached 84%. Early warning rank was I level (no alert status) in 1997 and 2009, but that in 2009 had a higher possibility to convert into II level. Likewise, the early-warning indices of sensitive ranks were different between 1997 and 2009. Population density, population growth rate, area index for tea garden, cultivated land owned per capita, level of drought, and investment for ecological and environmental construction were the main limiting factors to hinder the development of ecological security from 2009 to future. In general, the status of Wuyishan Scenery District ecological security was relatively good and considered as no alert level, while risk conditions also existed in terms of a few early warning indicators. We still need to pay more attention to serious alert indicators and adopt effective prevention and control measures to maintain a good ecological security status of this heritage site. PMID- 25129950 TI - [Effects of bacterial consortium EG03 on control of pepper bacterial wilt and rhizosphere microbial community characteristics in fields]. AB - Bacterial consortium EG03, consisted of several different antagonistic bacteria against Ralstonia solanacearum, was demonstrated to efficiently control bacterial wilt of pepper in field with a biocontrol efficacy of 85.8%. The traditional dilution plate method, the most probable number (MPN) method and Biolog system were adopted to determine effects of EG03 on characteristics of microbial community in pepper rhizosphere. It's shown that EGO3's effects on microbial community in pepper rhizospheric soil varied with time. There were an increase in the number of fungus and Bacillus spp. to some extent and a significant increase in that of nitrogen-fixing bacteria. Biolog analysis showed that the curve between average well color development (AWCD) and incubation time was S-shaped for all the treatments and that the AWCD of pepper rhizospheric soil at the early stage was higher than at the late stage. The analysis of carbon source utilization showed that EG03 decreased microbial utilization of carbon source in short-term, and the microbial community of pepper rhizospheric soil at the late stage composed mainly of microbes depended on sugars as carbon resource. EG03 treatment could decrease the five microbial diversity indices of rhizospheric microbes in short term, then increased those indices instead, especially with significant (P < 0.05) increases in Simpson index and McIntosh evenness. PMID- 25129951 TI - [Effects of inoculating plant growth-promoting rhizobacteria on the biological characteristics of walnut (Juglans regia) rhizosphere soil under drought condition]. AB - Effects of four plant growth-promoting rhizobacteria (PGPR) , namely Pseudomonas sp. YT3, Bacillus subtilis DZ1, B. cereus L90 and B. fusiformis L13 on the biological characteristics of walnut (Juglans regia) rhizosphere soil under drought stress were investigated. Results showed that drought stress had little effect on available nutrients of walnut rhizosphere soil, but significantly decreased the activity of organic carbon by 18.4% and increased the pH from 7.34 to 7.79. Under drought stress condition, the inoculation of Bacillus cereus L90 significantly increased high-labile organic carbon in walnut rhizosphere by 14.5% relative to the un-inoculated control, and decreased the pH to 7.41. Compared with the irrigated control, the total microbial populations, root exudates, microbial biomass carbon, and microbial biomass nitrogen in walnut rhizosphere soil were significantly decreased by 36.0%, 20.7%, 33.5% and 30.7%, respectively, because of drought stress. However, L90 inoculation decreased these deficits to 14.1%, 10.3%, 12.1% and 12.7%, respectively. Some terminal restriction fragments (T-RFs) disappeared under the drought condition and PGPR inoculation had great influence on T-RFs according to Terminal Restriction Fragment Length Polymorphism profiles. The Margalef index and the Shannon index of walnut rhizosphere soil significantly decreased, but the Simpson index increased relative to the irrigated control. Compared with the un-inoculated control, the Margalef index significantly increased from 0.42 to 0.99, as well as the Shannon index increased from 0.52 to 0.98. However, the Simpson index de- creased from 0.60 to 0.39. Inoculating YT3, DZ1 and L13 had weaker effects on the biological characteristics of walnut rhizosphere soil compared to inoculating L90, suggesting L90 inoculation could interfere with the suppression of drought stress to the biological characteristics of walnut rhizosphere soil. PMID- 25129952 TI - [Nest habitat quality evaluation for the oriental great reed warbler (Acrocephalus orientalis) in Baiyangdian Wetland]. AB - The Baiyangdian Wetland Natural Reserve is an important breeding habitat for oriental great reed warbler (OGRWs), Acrocephalus orientalis, in North China Plain. We investigated the nesting sites of OGRWs by line transect method during June-July, 2011, and 112 nests were found out in total. The ecological-niche factor analysis (ENFA) was applied in nesting habitat suitability assessment for OGRWs in Baiyangdian. The results showed that OGRWs in this reserve preferred nesting in dry land reed landscapes, which located at relatively high altitudes and away from anthropocentric disturbance. In 2011, the suitable and the most suitable nesting habitats of OGRWs in this reserve were 2474.69 hm2 and 1131.19 hm2, accounting 7.6% and 3.5% of the total reserve area, respectively. The most suitable nesting habitats shaped a circle-like structure, and they all clustered together around Damai and Shaoche core area, which located in the east part of the reserve. In order to protect the nesting habitats for OGRWs within Baiyangdian wetland reserve, it was suggested that the functional zone should be reorganized, and that the Damai and Shaoche core area should be integrated into one. This new core area would be bigger and more concentrated, at the same time the buffer zone should also be established appropriately, so as to protect the natural landscapes in this reserve as much as possible. PMID- 25129953 TI - [Photosynthetic activity of Gloiopeltis furcata (intertidal red macroalga) in response to desiccation]. AB - In this study, the diurnal change of photosynthesis activity in response to various tidal patterns, the relationship between photosynthetic activity and tissue water content, and the interactive effect of desiccation and irradiance on photosynthetic activity in Gloiopeltis furcata were investigated by using portable pulse amplitude modulated (PAM) fluorometer. Results showed that Fv/Fm decreased more rapidly during the noon low tide than during the morning- or evening low tide. F/Fm decreased slowly at the beginning of desiccation during the morning low tide, but decreased rapidly throughout the evening low tide. Fv/Fm recovered to the initial values on the same day no matter when the low tide occurred, suggesting the occurrence of dynamic photoinhibition. These features endowed G. furcata with an ability to adapt to the periodic desiccation on high intertidal rocks. The maximum (Fv/Fm) and effective (Phi(PSII)) quantum yield declined with the decrease of tissue water content (TWC). However, photosynthetic activity could recover completely when TWC exceeded 6%, showing a strong ability of G. furcata to tolerate desiccation. The relationships between TWC and Fv/Fm and Phi (PS II) as were as follows: F/Fm = 0.68 + (0.44-0.68)/[1 +(TWC/ 66.96)]5 , R2 = 0.99; Phi(PSII) = 0.585 + (0.004-0.585)/[1+(TWC/73)10], R2 = 0.99. ANOVA result further showed that the interactive effect of irradiance and desiccation on photosynthetic activity was significant, and that the photoinhibition degree increased with elevation of irradiation and duration of desiccation. The extreme condition (6 h desiccation at 1000 micromol photons x m(-2) x s(-1)) resulted in a serious photoinhibition, with the longest period of complete recovery for photosynthesis activity. PMID- 25129954 TI - [Seasonal variation of functional diversity of aquatic microbial community in Apostichopus japonicus cultural pond]. AB - The functional diversity of aquatic microbial communities in sea cucumber (Apostichopus japonicus) cultural ponds was examined in this paper. The Biolog plate technique and redundancy analysis (RDA) method were used to evaluate seasonal changes and their relationships with environmental factors. The results showed that both total amount and types of carbon sources utilized by microbes in the sea cucumber cultural ponds varied seasonally, and were the highest in summer and lowest in winter, with polymers being the main type of carbon sources. Principal component analysis revealed that the carbon utilization diversity of the microbial communities varied significantly over the seasonal courses. A total of 10 categories of carbon sources were significantly related to the principal component 1, among which were polymers, carbohydrates, carboxylic acids, amino acids, and amines. Significant seasonal changes were detected for all carbon utilization diversity indices of the microbial communities, including Shannon, McIntosh, Simpson, and S-E. However, seasonal variations were different among the microbial diversity indices. RDA analysis revealed that TP, NO(3-)-N, TN, and PO4(3-)-P were the critical environmental factors influencing the seasonal changes in functional diversity of aquatic microbial community in sea cucumber cultural ponds. PMID- 25129955 TI - [Estimation of biological parameters and yield per recruitment for Coilia nasustaihuensis in Dianshan Lake, Shanghai, China]. AB - Coilia nasustaihuensis is the most abundant species in Dianshan Lake and plays an important role in the lake ecosystem. From July 2010 to August 2011, a total of 3107 samples of C. nasustaihuensis were collected from Dianshan Lake. Based on length data of these samples, ELEFAN I technique was employed to estimate growth and mortality parameters, and the Beverton-Holt dynamic model was used to evaluate the population dynamics trend for C. nasustaihuensis. Growth of this species was described using avon Bertalanffy model, and the estimated parameters were Linfinity = 35.70 cm, k = 0.54, and t0 = -0.48 a. The turning point for body mass growth curve of the stock was situated at t = 1.37 a. Natural mortality coefficient M was then estimated using Pauly's empirical equation and found to be 0. 872. Length-converted catch curves were used to estimate the total mortality coefficient Z, which was found to be 2.121. Accordingly, the fishing mortality coefficient (F) was equal to 1.249, and the current exploitation rate was 0. 589, suggesting the stock was over-exploited. According to the Beverton-Holt dynamic model, the minimum capture size for C. nasustaihuensis should be 21.42 cm (age 1.22 years). PMID- 25129956 TI - [Effects of different host plants on the cold-resistant substances in overwintering larvae of Carposina sasakii Matsumura (Lepidoptera: Carposinidae)]. AB - To evaluate the influence of different host plants including apple, wild jujube, jujube, pear and hawthorn on the cold-tolerance substances in overwintering larvae of the peach fruit moth Carposina sasakii Matsumura, we measured the larvae super-cooling capacity, the water content (W), total fat content (TFC), total protein content (TPC) and total glycogen content (TGC) in the body. Results showed that the mean super-cooling point (SCPs) and freezing point (FPs) of overwintering larvae from the 5 host plant fruits differed significantly, ranging from -15.53 to -8.50 degrees C and -11.31 to -4.04 degrees C, respectively. The overwintering larvae fed on hawthorn owned the highest SCP, FP, TGC and the lowest W, while those fed on apple had the lowest SCP, FP, TFC and TGC but the highest W and TPC. The fresh mass (FM) of the overwintering larvae fed on pear was the highest, while those fed on jujube was very low. Those fed on jujube accumulated the highest TFC but the lowest TPC. PMID- 25129957 TI - [Accuracy of predicting in vitro ruminal methane production in goats using volatile fatty acids stoichiometric models]. AB - This study was conducted to investigate the accuracy of predicting in vitro ruminal methane (CH4) production using volatile fatty acids (VFA) stoichiometric models [CH4 = 0.5Ace-0.25Pro + 0.5But-0.25Val] (model 1), where CH4, Ace, Pro, But and Val are the production amounts of CH4, acetate, propionate, butyrate and valerate, respectively. Ten common feedstuffs, including four concentrates and six roughages with a wide range of chemical composition were incubated in serum bottles, and VFAs and CH4 production at 72 h were determined. The differences between the predicted and measured CH4 production were quantified using the model accuracy analysis. The results showed that the predicted CH4 production amounts were generally greater than the measured values obtained using the model 1, and the bias, slope and random error were 62.6%, 11.7% and 25.7%, respectively, indicating that fixed error exceeded 70%. By assuming 80% of total hydrogen being used for CH4 synthesis, the VFA stoichiometric model could be re-expressed as [CH4 = 0.8 (0.5Ace-0.25Pro + 0.5But-0.25Val)] (model 2). The root mean square prediction error (rMSPE = 0.18) for model 2 was less than for model 1 (rMSPE = 0.60). In addition, the bias, slope and random error of the model 2 were 2.1%, 5.7%, 92.3%, respectively, indicating that fixed error was less than 10%. In model 1, hydrogen formation resulting from VFA production were assumed to be totally consumed by methanogens for CH4 synthesis, without considering other pathways of hydrogen metabolism, which was the main factor resulting in the higher predicted values than the measured values. PMID- 25129958 TI - [Effects of plant viruses on vector and non-vector herbivorous arthropods and their natural enemies: a mini review]. AB - Plant viruses transmitted by arthropods, as an important biotic factor, may not only directly affect the yield and quality of host plants, and development, physiological characteristics and ecological performances of their vector arthropods, but also directly or indirectly affect the non-vector herbivorous arthropods and their natural enemies in the same ecosystem, thereby causing influences to the whole agro-ecosystem. This paper reviewed the progress on the effects of plant viruses on herbivorous arthropods, including vector and non vector, and their natural enemies, and on their ecological mechanisms to provide a reference for optimizing the management of vector and non-vector arthropod populations and sustainable control of plant viruses in agro-ecosystem. PMID- 25129959 TI - [Effects of iron on the algae growth and microcystin synthesis: a review]. AB - Iron, as one of the essential mineral elements for algae growth, plays an extremely important role in the physiological processes such as plant photosynthesis, respiration, nitrogen fixation, protein and nucleic acid synthesis. In view of the fact that iron in different forms could be absorbed and utilized by algae, the existing forms and circulation approaches in the aquatic environment, the absorption mechanism by algae, and the effects on algae growth and microcystin synthesis were reviewed in this paper. The relevant microcystin synthesis genes and their expression under iron restricted conditions were summarized, and the research directions for harmful algal blooms regulation and control by ferritin genes were suggested. It was hoped to provide the reference for eutrophication remediation technology. PMID- 25129960 TI - [Applications of stable isotope analysis in the trophic ecology studies of cephalopods]. AB - Cephalopods play an important role in marine food webs, however, knowledge about their complex life history, especially their feeding ecology, remains limited. With the rapidly increasing use of stable isotope analysis (SIA) in ecology, it becomes a powerful tool and complement of traditional methods for investigating the trophic ecology and migration patterns of invertebrates. Here, after summarizing the current methods for trophic ecology investigation of cephalopods, applications of SIA in studying the trophic ecology of cephalopods were reviewed, including the key issues such as standardization of available tissues for SIA analyzing, diet shift and migration patterns of cephalopods, with the aim of advancing its application in the biology of cephalopods in the future. PMID- 25129961 TI - [Control study on risk factors of children with secretory otitis media nested case]. PMID- 25129962 TI - [Mutation screening in taperin gene in Chinese with prelingual nonsyndromic hearing impairment]. AB - OBJECTIVE: To screen and identify the frequency and characteristic of mutation in stereocilium-related gene Taperin of Chinese prelingual nonsyndromic hearing impairment with DNA microarray combined with PCR. METHOD: One hundred and thirty four patients of prelingual nonsyndromic deafness and one hundred health individuals in China were investigated in this study. Genomic DNA was extracted from the patients and was subjected to DNA microarray to screen mutations in 4 most common genes. The samples that carried none of the common mutant alleles were subjected to PCR and sequenced to detect mutations in Taperin gene. RESULT: Ninteen out of one hundred and thirty-four patients of prelingual nonsyndromic deafness were detected carring common deafness gene with DNA microarray. Taperin gene were detected in one hundred and fifteen patients with PCR. A187S was detected in Taperin as hetrozygous state in 2 patients and their unaffected members of their family. It occurred at the evolutionary conservation of the amino acids of taperin according to alignment analysis. Two polymorphism, 157C>T and 318C>T, were found in the patients and the control group. CONCLUSION: A novel Taperin mutation, A187S was detected in Chinese patients with prelingual nonsyndromic hearing loss, which may be relevant to hearing loss. Two polymorphism, 157C>T and 318C>T, were found in Chinese in our research. The carrier frequency for Taperin mutation is about 1.74% of prelingual nonsyndromic deafness in Chinese patients. PMID- 25129963 TI - [Analysis on GJB2 gene mutations with nonsyndromic hearing impairment in Kazak patients of Xinjiang]. AB - OBJECTIVE: To study mutations in the GJB2 gene in Kazak patients with nonsyndromic hearing impairment from Xinjiang. METHOD: One hundred and ninety three cases of Kazak from the Xinjiang region, including 97 cases of hearing loss and 96 cases of normal people, were performed mutational analysis of the GJB2 coding region by PCR-direct sequencing. RESULT: Eight kinds of mutation were found in the encoding region of hearing impairment group:12 cases of 35 delG homozygous, 5 cases of 79G>A homozygous, 8 cases of 79G>A heterozygous, 1 case of 79G>A heterozygous and 608T>C heterozygous, 5 cases of 79G>A heterozygous and 341A>G heterozygous, 4 cases of 235 delC heterozygous, 2 cases of 341A>G heterozygous, 1 case of 439T>G heterozygous, 1 cases of 457G> A heterozygous, 2 cases of 521G>A homozygous. Four kinds of mutations found in the normal group were confirmed as common polymorphic mutation. CONCLUSION: The study suggests that the GJB2 gene mutation of the Kazak deaf population in Xinjiang has ethnic and regional characteristics. There is a rather high carrier frequency of GJB2 mutation of Kazak patients in Xinjiang. In this study the 35 delG mutation is a common mutation of Kazak patients. PMID- 25129965 TI - [Clinic significance of CT scan in diagnosis and management unsudden unilateral sensorineural hearing loss]. AB - OBJECTIVE: To investigate the clinic significance of the temporal bone high resolution CT in discovering unilateral sensorineural hearing loss of adolescents, and to provide the basis for the rational using of medical resources. METHOD: A retrospective study was conducted on 28 outpatients with unilateral sensorineural hearing loss at unsure time. Their medical history and CT examine were reevaluated,combined with associated articles in this report. RESULT: All of the 28 patients with unilateral sensorineural hearing loss had the normal external ear and middle ear and received CT scan. Nine out of twenty-eight cases had inner ear malformation. Among the nine cases, 1 cases was Mondini malformation and 1 cases was common cavity, 5 cases were single stenosis of IAC, and 2 cases were semicircular canal and vestibular malformation. 19 cases were not found abnormal by CT, and 4 cases had had suffered from mumps. CONCLUSION: CT scan was available in diagnosis of unsudden unilateral sensorineural hearing loss, which would help us to use medical resource more rationally. PMID- 25129964 TI - [DNA microarray screening analysis in children with profound hearing impairment in Hubei province]. AB - OBJECTIVE: To investigate characteristics of molecular etiology of children with profound sensorineural hearing loss in Hubei province, and to provide reference for deafness treatment and genetic counseling. METHOD: Three hundred and six children with profound sensorineural hearing loss in Hubei province were enrolled, their genomic DNA were extracted from peripheral blood and a deafness gene test chip was used to screen nine hot spot mutation in the GJB2, GJB3, SLC26A4, and mitochondria 12SrRNA gene. All patients with SLC26A4 gene mutation were given temporal bone CT scan. RESULT: One hundred and thirty-two (43.14%) out of 306 children were found carrying at least one pathogenic gene mutation. The mutation rates of GJB2, SLC26A4 and mitochondria DNA 12SrRNA gene were 29.41% (90/306), 13.72% (42/306) and 0.65% (2/306), respectively. None out of 306 children was detected GJB3 gene mutation. Thirty-six patients carrying SLC26A4 gene mutation were detected enlarged vestibular aqueduct by CT scan. CONCLUSION: Mutations of GJB2 and SLC26A4 gene are two major pathogenic gene for genetic hearing loss in children. 235delC mutation is the main mutation type, followed by IVS7-2A> G mutation type. The screening of SLC26A4 gene common mutations contribute to the diagnosis of enlarged vestibular aqueduct syndrome. PMID- 25129966 TI - [Cochlear implantation in patients with cochlear ossification]. AB - OBJECTIVE: To investigate cochlear implantation surgical techniques and postoperative results in patients with cochlear ossification. METHOD: Twenty-nine cochlear ossification patients with cochlear implantation in our department were retrospectively studied during 1997-2011. Preoperative imaging and electrophysiological assessment were done to classify the cochlear ossification of all the patients. Categories of auditory performance and speech intelligibility rating were detected to assess the outcome of cochlear implant postoperatively. RESULT: Among 29 cases with cochlear ossification, 19 cases were grade II, 4 cases were grade I, 4 cases were grade III, and 2 cases were apical turn ossification. Among 23 patients with cochlear ossification grade I and II, 17 cases were totally cochlear array insertion, and 6 cases were partial cochlear array insertion. Patients with cochlear ossification grade III were all partial cochlear array insertion. Most patients achieved good hearing and language ability after cochlear implantation. CONCLUSION: Cochlear implantation can be successfully performed on the basis of systematic preoperative assessment and some patients can achieve good postoperative results in patients with cochlear ossification. Intraoperative electrical stimulation of the auditory evoked response provides a good method to assess the residual spiral nerve function. PMID- 25129967 TI - [Complementary self-treatment for posterior canal benign paroxysmal positional vertigo]. AB - OBJECTIVE: To examine the value of self-treatment for Posterior canal benign paroxysmal positional vertigo (PC-BPPV). The treatment effect was compared between patients treated with modified Epley in outpatient clinic combined with self treatment at home and patients treated by modified Epley alone. METHOD: A randomized controlled trial were carried out in the Department of Otolaryngology Head and Neck Surgery, the Affiliated Sixth People's Hospital of Shanghai Jiao Tong University from December 2012 to May 2013. 147 out of 150 patients with unilateral idiopathic BPPV-PSC were enrolled in follow-up. Among which, 73 patients were allocated in modified Epley-alone group and 74 were allocated in slef-treatment group. RESULT: The success rate was 53.4% in modified Epley-alone group vs 83.8% in self-treatment group (P < 0.01) after 1 week treatment. In the modified Epley-alone group,the success rate of hand repositioning group and chair assisted repositioning group was 45.9% vs 61.1% (P > 0.05), the risk rate was 0.752, 95% CI (0.486 - 1.163). In the self-treatment group, the success rate of hand repositioning group and chair-assisted repositioning group was 87.5% vs 81.0% (P > 0.05), the risk rate was 1.081, 95% CI (0.888-1.316). Incidence rate of serious complications was 0% in the modified Epley-alone group and 1.3% in the self-treatment group (P > 0.05). CONCLUSION: Complementary self-treatment with modified Epley maneuver treated PC-BPPV sooner and more effectively, Compared with modified Epley maneuver alone. And its incidence rate of serious complications didn't increase. Chair-assisted repositioning showed better result than hand repositioning alone, and self-treatment at home can reduce the effect of the gap. We found that complementary self-treatment with modified Epley maneuver had more benefits for patients with PC-BPPV. PMID- 25129968 TI - [Research of cochlear coiling pattern and orientation in general population by CT 3D reconstruction]. AB - OBJECTIVE: To perform morphometric analysis of bilateral cochleae in all subjects based on computed 3-dimensional reconstruction tomographic data and assist the surgeon in diagnosing the inner ear abnormality or surgical strategies. METHOD: Two hundred normal developed cochleae from 100 patients were divided into 5 groups according to age. Morphometric analysis of bilateral cochleae was performed in all subjects by 3D reconstructions and 2D multiplanar reformation. The length and width of the cochlear base, the length within the cochlear base, the height of the cochlea, the angle between the first and second turn of the cochlea, and the cochlear orientation within the cranial base were measured and compared in different age, sex and bilateral groups. RESULT: The length of the cochlear base was (8.56 +/- 0.52)mm, the width was (6.63 +/- 0.56)mm, the length within the cochlear base was (7.33 +/- 10.56)mm, the height of the cochlea was (3.76 +/- 0.28)mm, and the angle between the first and second turn of the cochlea was (15.82 +/- 2.78)degrees. All index above did not change significantly in different aging, sex or side (P > 0. 05). Variability in the angle between the first and second turn of the cochlea was considerable, and a smaller angle (from the midsagittal line) was showed in the older age groups than the younger groups (P < 0.05). CONCLUSION: 3D and 2D volume rendering enables us to evaluate the features of cochlear morphology and orientation that may assist the surgeon in diagnosing the inner ear abnormality or surgical strategies. PMID- 25129969 TI - [A comparison of 226 Hz and 1 000 Hz tympanometry in diagnosis of infants otitis media effusion]. AB - OBJECTIVE: To provide a clinical reference by comparing the conventional 226 Hz tympanometry with 1000 Hz tympanometry in two groups of young children with otitis media effusion evidenced by CT scan. METHOD: One hundred and seventy-seven young children (226 ears), from 1 to 60 months, with otitis media effusion were involved in this study. They were divided into six groups by age: 0-6 months group, 6-12 months group, 12-18 months group, 18-24 months group, 24-36 months group, 36-60 months group. They were tested with tympanometry of 2 probe-tones of 226 and 1 000 Hz. Type A tympanogram was defined as a normal middle ear function in 226 Hz and single-or double-peak in 1 000 Hz tympanometry. One hundred and fifty-eight normal young children (266 ears) were selected as control group. The results were analysed with Chi square test. Receiver operator characteristic (ROC) analysis was performed to evaluate the two methods. RESULT: In the young children with otitis media effusion, the detection rate of 226 Hz tympanogram in six groups was 21.1%, 35.2%, 46.9%, 42%, 62.5% and 68% respectively, while 94.7%, 98.1%, 96.9%, 91.2%, 95.8% and 88% respectively in 1 000 Hz tympanogram. In the young children with normal middle ear function, the detection rate of 226 Hz tympanogram in six groups was 95.1%, 88.6%, 85.1%, 93.3%, 88.5% and 93.5%, while 87.8%, 94.3%, 89.4%, 95.6%, 94.2% and 97.8% respectively in 1 000 Hz tympanogram. The detection rate was significantly different between 226 and 1 000 Hz tympanogram in the young children under 36-month old. CONCLUSION: A single-or double-peak 1000 Hz tympanometric patterns as normal criteria was a simple way to evaluate young children s' middle ear function. 1 000 Hz tympanometry should be given priority to the children within 36-month old in detection middle ear function,the 226 and 1 000 Hz tympanometry should be done at the same time within 36-60 months old. PMID- 25129970 TI - [Analysis of TEOAE and AABR hearing screening and follow-up in NICU]. AB - OBJECTIVE: To study the results of TEOAE and AABR hearing screening and follow-up in NICU. METHOD: Total 574 cases in NICU were included in this study, all cases received both TEOAE and AABR hearing screening while admission and rescreening when one-month-old. The cases that were abnormal on either test in rescreening were asked to return for diagnostic tests at 3 moths old. The patients who didn't return as required in 3 months were surveyed by call and analyzed. RESULT: Among 574 cases, 472 cases passed both TEOAE and AABR hearing screening while admission. While 102 cases had abnormal test results in either screening test. Thirty-three cases returned for follow-up, 13 of which passed rescreening test one month after discharge, the other 20 cases had ABR diagnostic tests after 3 months. Among them, 8 cases had normal hearing, 12 cases had various degree of hearing loss. Sixty-nine cases lost follow-up. The reason of lost follow-up was as follows, parents changed phone number/contact information, parents didn't understand the screening results, parents believe that their children having no need for further testing; parents had retest in other hospitals, parents didn't pay attention to hearing loss because of other severe complicated comorbidities. CONCLUSION: The passing rate (normal) of TEOAE and AABR hearing screening in NICU was 82.2%, non- passing rate wass 17.8%, and the prevalence of hearing loss was high in those followed cases. Hyperbilirubinemia was the main risk factors of hearing loss in our NICU patients. We reviewed the reason for high rate (67.6%) of losing follow-up. PMID- 25129971 TI - [Effect of ossicular chain reconstruction with titanium ossicular replacement prosthesis in mastoidectomy with synchronous ossiculoplasty]. AB - OBJECTIVE: To assess hearing effect of ossicular chain reconstruction with titanium ossicular replacement prosthesis during mastoidectomy with synchronous ossiculoplasty in chronic middle ear disease. METHOD: Retrospective reviews were performed for 139 patients who had underwent mastoidectomy and tympanoplasty with titanium ossicular replacement prostheses at the same time between 2008 and 2011. The partial ossicular replacement prostheses (PORP) were used in 91 patients and the total ossicular replacement prostheses (TORP) were used in 48 patients respectively. All patients had follow-up for 2 to 5 years. The preoperative and postoperative mean air conduction and air-bone gaps(ABG) for the four frequencies (0.5, 1.0, 2.0 and 4.0 kHz) were evaluated. The improvement of mean air conduction and ABG over the same frequencies were measured. A postoperative ABG less than or equal to 20 dB was considered a successful operation. The hearing results of titanium PORP and TORP were compared. RESULT: The mean air conductions were (53.97 +/- 11.32)dB and (36.80 +/- 11.68) dB preoperatively and postoperatively in PORP group. The mean improvement in air conduction was (17.17 +/- 5.79)dB. The mean ABG was (31.84 +/- 6.17)dB and (15.13 +/- 7.22)dB preoperatively and postoperatively in PORP group. The mean improvement in ABG was (17.71 +/- 5.5)dB. The difference of hearing threshold between preoperative and postoperative had statistical significance (P < 0.01). The mean air conduction were (58.05 +/- 11.35)dB and (44.53 +/- 13.15)dB preoperatively and postoperatively in TORP group. The mean improvement in air conduction was (13.52 +/- 7.81)dB. The mean ABG; were (35.67 +/- 5.73)dB and (21.48 +/- 7.01)dB preoperatively and postoperatively for TORP group. The mean improvement of hearing threshold in ABG was (14.18 +/- 7.53)dB. The difference of hearing threshold between preoperative and postoperative had statistical significance (P < 0.01). ABG less than 20 dB after operationwas happened in 68.63% of the patients (74.73% for PORP and 54.17% for TORP). There was statistically significant difference between PORP and TORP (P < 0.05). CONCLUSION: We conclude that titanium ossicular reconstruction during mastoidectomy with synchronous ossiculoplasty give stable and excellent hearing results. We obtained better results with PORP than with TORP. PMID- 25129972 TI - [Paraglottic space primary paraganglioma: a case report and review]. AB - OBJECTIVE: To investigate the clinical feature, diagnose and therapeutic methods of paraglottic space primary paraganglioma. METHOD: One case of paraglottic space primary paraganglioma was reported and the relevant literatures were reviewed. RESULT: One case showed a hoarse voice, who was cured after the surgery of neck incision. NSE and CgA were positively expressed. CONCLUSION: Paraganglioma of the paraglottic space is very rare. The diagnosis of paraglottic space primary paraganglioma bases on histopathology and immunohistochemistry. The immunohistochemistry and clinical character must be comprehensively analyzed to increase the diagnosis accuracy. PMID- 25129973 TI - [Comparison of application of several psychophysical olfactory test methods in clinic]. AB - OBJECTIVE: To compare the consistency of four olfactory psychophysical test methods. METHOD: Twenty out-patients were done with olfactory psychophysical test and the results were analyzed. The four olfactory psychophysical test methods include simple test method, UPSIT, Sniffin Sticks test and the T&T olfactometer test. RESULT: The consistency of four test methods reached 85%, and UPSIT test can identify pseudo smell obstacles. CONCLUSION: There is reliable and stable outcome of the four psychophysical olfactory test methods. PMID- 25129974 TI - [Investigation of skin prick test on patients with allergic rhinitis in Urumqi area]. AB - OBJECTIVE: To investigate the geographic distribution of air-borne allergens which caused allergic rhinitis in Urumqi, and offer guide for prevention and treatment of the patients with allergic rhinitis. METHOD: Skin prick tests were performed on 350 patients with allergic rhinitis by assay of Novo-helisen depot (NHD) fluid. RESULT: The total positive rate of inhaled allergens among 350 patients was 78.86%. The most frequent of allergen was chenopodium 78.86% (255 cases). The other frequent allergens were ragweed 36.86% (128 cases), artemisir 28% (98 cases), timothy 27.14% (95 cases), elm 5.71% (90 cases), willow 25.14% (88 cases), poplar 18.86% (66 cases), cockroach 18.86% (66 cases), dust-mite 14.86% (62 cases), flour mite 14.86% (52 cases), alternaria spp 2.86% (10 cases). Allergen were multiple in most AR patients. There was not statistically significant difference between the sexes. There was statistically significant difference between the tribes. CONCLUSION: Chenopodium, ragweed and artemisir were the main allergens in patients with allergic rhinitis in Urumqi. PMID- 25129975 TI - [Effect of ambroxol on biofilm of Haemophilus influenzae and bactericidal action]. AB - OBJECTIVE: To establish a biofilm model of Haemophilus influenzae and observe the effect of ambroxol on biofilm of Haemophilus influenzae and bactericidal action. METHOD: Thirty strains of Haemophilus influenzae were isolated from adenoids of children with adenoidal hypertrophy. Two strains which could build stronger biofilms was selected in a 96-well plate. The effect of ambroxol on biofilms were determined by crystal violet, and the structure of biofilms were observed by scanning electron microscope (SEM). The numbers of viable bacterial in biofilm after ambroxol treatmented determined by plate culture count. RESULT: Through crystal violet assay, significant difference (P < 0.01) between the two group after treatment was found when ambroxol concentration reached at 0.25 mg/ml and 0.49 mg/ml. The biofilms was destroyed by SEM. Ambroxol had the positive effect on bacterial killing by plate culture count,and the effect was in a dose dependent. CONCLUSION: Ambroxol could destroy the biofilm of Haemophilus influenzae, and had bactericidal function in vitro. PMID- 25129976 TI - [Multiple factors quantitative analysis on middle ear function in primarily diagnosed patients with nasopharyngeal carcinoma]. AB - OBJECTIVE: To explore the ways of quantitative and objective evaluation for analyzing the multiple influence factors on middle ear function in the patients with primarily diagnosed NPC, and to analyze the influence factors of middle ear function in the patients with primarily diagnosed nasopharyngeal carcinoma (NPC). METHOD: Three hundred and twenty cases (320 ears) of primarily diagnosed NPC patients were examinated with electric otoscope, acoustic immittance measurement, pure tone audiometry, nasopharynx and middle ear CT or MRI scanning, eustachian tube function examination, and electronic nasopharyngoscope. A series of quantitative methods, as the influence factors including T stage, clinical stage, location, diffusion type and form of tumor, eustachian tube function, pharynx mouth shape, imaging extension (nasal, skull base, pharyngeal recess, parapharyngeal space, tensor veli palatini muscle, levator veli palatini and so on), were used to evaluate the middle ear function. SPSS 13.0 was used to anlyze the single and multiple factors in statistics. RESULT: T stage, clinical stage, location, diffusion type, and form of tumor, pharynx mouth shape, imaging extension (nasal, skull base, pharyngeal recess, parapharyngeal space, tensor veli palatini muscle, levator veli palatini) were the single influence factors on the function of middle ear in primarily diagnosed NPC patients. The gender, age, pathological types, N staging and M staging of NPC patients primarily diagnosed had no effect on middle ear function. The multple factors analysis showed that T stage, tumor location, the function of eustachian tube, tensor veli palatini muscle invasion, and skull base invasion were independent factor of affecting the middle ear function on primarily diagnosed NPC patients. CONCLUSION: In this study, the influence factors of middle ear function with primarily diagnosed NPC were related to T stage, location of tumor, the function of eustachian tube, tensor veli palatini muscle invasion, skull base invasion, otitis media and quantitative criteria. The way of quantitative analysis could be used to evaluate objectively the middle ear function in patients with primarily diagnosed NPC. PMID- 25129977 TI - [Silenced NgR gene expression by RNA interference to promote rats facial nerve regeneration in vitro]. AB - OBJECTIVE: To suppress NgR gene expression in neural stem cells and observe differentiation of neural stem cells in vitro after interfered which provide nutritional support for the facial nerve repair in vivo. METHOD: PCR amplification, restriction endonuclease digestion, T4DNA ligase connections were used to connected NgR with rector pGCsi, and constructed recombinant vector (NgR shRNA). Lipofectamine 2000 were used to transfect the NSC. The expression of NgR was examined by Western Blot. The proportion of neural stem cells transformed into neurons after transfection was tested by Immunocytochemistry. Neural stem cells were planted in PLGA tubes after transfected, and were scanned by electron microscopy. RESULT: NgR shRNA plasmid was constructed and infected neural stem cells successfully. Western Blot showed that the expression of NgR decreased in neural stem cells after interference. Immunocytochemistry showed that the rate of the neural stem cells transformed into neurons after interfered was significantly higher (P < 0.01). CONCLUSION: Neural stem cells were transformed into neurons after NgR shRNA plasmid infected neural stem cells, which promoted axonal regeneration more effectively and provided a efficient and stable gene platform for facial nerve repair. PMID- 25129978 TI - [The effect of forsythiaside on the expression of c-jun induced by cisplatin in the cochlea of guinea pig]. AB - OBJECTIVE: To study the effect of forsythiaside on the expression of c-jun induced by cisplatin in the cochlea of guinea pig. METHOD: Thirty guinea pigs were randomly divided into control group (10), cisplatin group (10) and forsythiaside group (10). The ototoxicity model was done with intraperitoneal injection of cisplatin solution (8 mg/kg per day) for 7 days. Forsythiaside (25 mg/kg per day) was injected 30 min before cisplatin solution treated in guinea pigs of forsythiaside group for 7 consecutive days. The saline instead of cisplatin was injected in normal control group. The distortion product otoacoustic emission (DPOAE) was detected before animals were killed. The expression of c-jun in cochlea of guinea pigs was detected by western blotting. The expression of c-jun mRNA in cochlea of guinea pigs was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULT: DPOAE amplitudes in cisplatin group was significantly lower than in control group (P < 0.01). Compared with cisplatin group, DPOAE amplitudes in forsythiaside group was increased significantly (P < 0.05). The expression of c-jun protein and mRNA were significantly increased in cisplatin group than in control group (P < 0.01). Compared with cisplatin group, the expression of c-jun protein and mRNA were significantly decreased in forsythiaside group. CONCLUSION: Forsythiaside can significantly reduce the side effects induced by cisplatin through down regulating the expression of c-jun. PMID- 25129979 TI - [Clinical efficacy of mouse nerve growth factor in the treatment of sudden deafness]. AB - OBJECTIVE: To study the clinical efficacy of mouse nerve growth factor (NGF) in the treatment of sudden deafness. METHOD: A retrospective analysis was performed on 115 cases of hospitalized patients who were suffered from sudden deafness. Patients were divided into two groups according to treatment medicine. Control group: patients were treated with intravenous vasodilators, energy mixture, steroid pulse therapy, and methylcobalamin neurotrophic therapy. NGF group: intramuscular NGF treatment was added on the basis of conventional therapy mentioned above. Both treatments lasted 14 days, the total efficiency were compared. Patients were further divided into sub-groups according to age, duration and the level of pre-treatment PTA, and the treatment efficiency was further compared. By SPSS 11.0 statistical analysis, a P < 0.05 was considered as statistical significant difference. RESULT: (1) The total efficiency of NGF group was significantly higher than control group. (2) Regard of age, the efficiency of NGF treatment group was significantly higher than control group. (3) For the patients whose duration were less than 7 d, or the PTA < or = 60 dBHL, the efficiency of NGF group were significantly higher. For the patients whose duration were more than 7 d, or the PTA>60 dBHL, the efficiency of NGF therapy was not superior to the traditional treatment. CONCLUSION: NGF can significantly improve the symptom of patients with short duration or low PTA. For this kind of patients, NGF adjuvant therapy should be recommended. For the patients with longer duration and higher level of PTA, NGF therapy is not advocated. NGF treatment should not be in consideration of the age. PMID- 25129980 TI - [The clinical application of modified rhytidectomy incision in superficial parotid tumor surgery]. AB - OBJECTIVE: To evaluate the modified rhytidectomy incision in superficial parotidectomy. METHOD: Thirty-five patients with superficial parotid tumor were included in this study. A modified rhytidectomy incision often used in facial plastic surgery was used for superficial parotidectomy and subtotal superficial parotidectomy with preservation of facial nerve and great auricular nerve. The follow-up study included the exposed region, the cosmetic effect of this approach and the rate of complication. RESULT: All patients healed without salivary fistula, and were satisfied with this modified approach. Temporary paralysis of the marginal mandibular branch of facial nerve were found in five patients, and six patients felt insensible around earlobe after operation. They all recovered in 1 to 3 months after surgery, no recurrence was happened during follow-up in 36 to 60 months (median follow-up period was 48 months). CONCLUSION: The modified rhytidectomy incision provided good exposure, had less complication and better cosmetic outcome. PMID- 25129981 TI - [Microsurgical efficacy of cholesteatoma of external auditory canal combined with filling drugs by ear endoscopy]. PMID- 25129982 TI - [Perioperative treatments of congenital microtia with auricular reconstruction]. PMID- 25129983 TI - [The position and protection of the vertical facial nerve during cochlear implantation guided by HRCT]. PMID- 25129984 TI - [The development and application of MRI of the inner ear after gadolinium injections in the diagnosis of Meniere's disease]. AB - Due to the lack of objective examination method, the diagnosis of Meniere's disease mainly relies on subjective symptoms. MRI of the inner ear after gadolinium injections had become a new technology in otology in recent years. The image can clearly distinguish perilymph from endolymph in the labyrinth and can be applied to the imaging diagnosis, evaluation of treatment and the pathogenesis research of Meniere's disease. This article is a review of the development and the application in clinical research of this new technology. PMID- 25129985 TI - [The giant mucous cyst of frontoethmomaxillary sinus: one case report]. AB - One case of rare giant mucous cyst of nasal sinus that implicated frontal, ethmoid and maxillary sinus was in our hospital. The patient manifested mainly slowly developing swelling and pain of cheek, exophthalmos and visual impairment. The image studies indicated cyst of nasal sinus, including frontal, ethmoid, and maxillary sinuses. The clinical diagnosis was cyst of frontoethmomaxillary sinus. PMID- 25129986 TI - Carboplatin dosing for adult Japanese patients. AB - Carboplatin is a platinum-based anticancer drug that has been long used to treat many types of solid cancer. Because the clearance of carboplatin strongly correlates with the glomerular filtration rate (GFR), its dosage is calculated with the Calvert formula on the basis of the patient's GFR to achieve the target area under the plasma drug concentration-time curve (AUC) for each patient. However, many lines of evidence from previous clinical studies should be interpreted with caution because different methods were used to estimate drug clearance and derive the dosage of carboplatin. There is a particularly high risk of carboplatin overdosing when the dosage is determined on the basis of standardized serum creatinine values. When deciding the dose of carboplatin for adult Japanese patients, preferred methods to assess renal function instead of directly measuring GFR include (1) 24-h urinary collection-based creatinine clearance adjusted by adding 0.2 mg/dl to the serum creatinine concentration measured by standardized methods, and (2) equation-based GFR (eGFR) with a back calculation to units of ml/min per subject. Given the limitations of serum creatinine-based GFR estimations, the GFR or creatinine clearance should be directly measured in each patient whenever possible. To ensure patient safety and facilitate a medical-team approach, the single most appropriate method available at each institute or medical team should be consistently used to calculate the dose of carboplatin with the Calvert formula. PMID- 25129987 TI - Retrospective case series of 15 patients treated with chemoradiation using 5-FU and nedaplatin for gynecological malignancy: with regard to hemotoxicity. AB - We conducted a retrospective comparison of the hemotoxicity of the sequential administration of 5-Fluorouracil (5-FU) prior to Nedaplatin (NDP) (FN therapy) and that of its reverse sequence (NF therapy) for gynecological malignancy. From February 2002 to November 2004, a total of 15 gynecological malignancy patients were treated with radiation therapy combined with NDP and 5-FU. Of these 15 patients, 5 were treated with NF therapy, and 10 were treated with FN therapy. No significant differences were detected between the FN and NF groups with regard to white blood cell count (WBC), hemoglobin level (Hb), and platelet count. The results of this study do not show that the FN group has a lesser degree of hemotoxicity than the NF group. PMID- 25129988 TI - Family support for women's health-seeking behavior: a qualitative study in rural southern Egypt (Upper Egypt). AB - This qualitative study investigated the influence of family support on women's health-seeking behavior in rural southern Egypt (Upper Egypt). We carried out separate focus group discussions (FGDs) with 3 groups (6 women with children under 5 years old, 6 men, and 4 elderly women, respectively) in a village in Assiut Governorate, an underprivileged region in Upper Egypt. The FGDs aimed to identify how different types of family support affected women's health-seeking behavior in areas including maternal health and common illnesses of women and children. Our results showed that maternal health issues were often discussed by husbands and wives, while mothers-in-law had little apparent influence. We also found that women could access support resources more easily than expected through their extended families. Our study showed that husbands had an important role in encouraging women's health in the family, while the effect of mothers-in-law on women's health-seeking behavior was not substantial. The study indicated that women received considerable support from co-resident family members, their natal family, and their neighbors, which helped women in seeking health services. PMID- 25129989 TI - Useful base plate to support the head during Leksell skull frame placement in gamma knife perfexion radiosurgery. AB - We developed an original base plate to support both the patient's head and a Leksell stereotactic skull frame during frame placement in the supine position. The base plate is made of transparent acrylic board with holes at the posterior posts for injection of local anesthetics and maneuver of fixation screws through them. A stable and comfortable position of the patient's head in a supine position is obtained and maintained on this base plate with an air-pressure cuff beneath the patient's head. The patient is able to keep a stable, relaxed and comfortable posture during the procedures of skull frame placement. PMID- 25129991 TI - A learning curve in aortic dissection surgery with the use of cumulative sum analysis. AB - This study demonstrates the risk adjusted cumulative sum analysis of an individual surgical learning curve for acute type A aortic dissection surgery. Thirty consecutive patients were operated by a single surgeon for acute type A aortic dissection from April 2001 to March 2008. Operative variables, mortality, and major morbidities were analyzed. The learning curve was calculated by cumulative sum analysis. The anticipated 30-day operative mortality rate was 20.2 +/- 12.7% (range, 3.3-56.7%) and the expected 30-day mortality and morbidity rate was 47.0 +/- 13.3% (range, 21.7-70.6%) according to the Japan SCORE calculator. The observed operative and in-hospital mortality rate was 6.67% (two patients), and the observed major postoperative morbidity rate was 10.0% (three patients). Risk-adjusted cumulative sum analysis revealed that no excess deaths occurred beginning at the seventh case and thereafter. The surgeries for acute type A aortic dissection could be performed at the professionally permissive level from the beginning. Risk-adjusted cumulative sum analysis was a useful tool to monitor the performance of the surgical procedure. PMID- 25129990 TI - Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal model of metabolic syndrome. AB - Aging is accelerated by metabolic and cardiovascular diseases, and the risk of these diseases increases with age. Obesity is an important risk factor for many age-related diseases and is linked to reduced telomere length in white blood cells. We investigated whether cardiac senescence might be enhanced in DahlS.Z Lepr(fa)/Lepr(fa) (DS/obese) rats, which we recently established as a new animal model of metabolic syndrome. The heart of DS/obese rats was compared with that of homozygous lean littermates (DahlS.Z-Lepr+/Lepr+, or DS/lean, rats). DS/obese rats manifested hypertension as well as left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 18 weeks of age. Myocardial oxidative stress and inflammation were increased in DS/obese rats compared with DS/lean rats. Telomere length in myocardial cells did not differ between the two rat strains, whereas telomerase activity and expression of the telomerase reverse transcriptase gene were increased in DS/obese rats. Expression of the senescence-associated genes for checkpoint kinase 2 (Chk2), p53, and p21 as well as that of genes related to the renin-angiotensin-aldosterone system were also up-regulated in the DS/obese rat heart. Our results indicate that DS/obese rats undergo premature cardiac senescence as well as cardiac remodeling in association with the development of diastolic dysfunction in these animals. PMID- 25129993 TI - A novel method for managing water and electrolyte balance after transsphenoidal surgery: preliminary study of moderate water intake restriction. AB - Hyponatremia is a common and potentially serious complication of transsphenoidal surgery (TSS). Since September 2009, we have implemented moderate water intake restriction (< 2500 mL/day) after TSS in an attempt to prevent this complication. The aim of this study was to investigate the efficacy of a combination of moderate restriction of water intake plus antidiuretic hormone (arginine vasopressin [AVP]) replacement therapy in patients with diabetes insipidus (DI) for reducing the incidence of delayed hyponatremia after TSS. Patients treated from September 2005 to August 2009 were allowed to drink water freely after surgery (the control group), while patients treated from September 2009 to June 2012 were restricted to less than 2500 mL water per day (the water restriction group). To reduce the occurrence of hypernatremia, AVP replacement therapy was provided immediately after the development of DI. We retrospectively analyzed the incidence of hyponatremia, DI, and hypernatremia in patients following TSS. Hyponatremia incidence was significantly lower in the water restriction group (P = 0.017); however, there were no significant differences in DI incidence and hypernatremia incidence between the 2 groups. Under DI control with AVP replacement therapy, the water restriction group showed no significant difference in the daily self-rated thirst level for the patients with and without DI. Moderate water intake restriction in addition to AVP replacement therapy significantly decreases the incidence of hyponatremia without patient discomfort (extreme thirst) and other complications. However, further studies are required to determine the most effective amount of water and the optimal duration of postoperative water restriction. PMID- 25129992 TI - Glucocorticoids activate cardiac mineralocorticoid receptors in adrenalectomized Dahl salt-sensitive rats. AB - We previously showed that selective mineralocorticoid receptor (MR) blockade by eplerenone is cardioprotective in Dahl salt-sensitive (DS) rats. To clarify the consequences of glucocorticoid-mediated MR activation in these animals, we investigated the effects of exogenous corticosterone on blood pressure as well as cardiac remodeling and function after adrenalectomy. DS rats were subjected to adrenalectomy at 6 weeks of age and thereafter fed a high-salt diet and administered corticosterone (20 mg/kg per day) or vehicle. Systolic blood pressure was higher in the corticosterone group than in the vehicle group at 7 weeks and thereafter. By 11 weeks, corticosterone had reduced left ventricular (LV) mass and induced LV diastolic dysfunction. The ratio of collagen type I to type III mRNA levels in the left ventricle was increased in the corticosterone group compared with the vehicle group. Administration of a non-antihypertensive dose of the MR antagonist spironolactone (20 mg/kg per day) from 6 weeks inhibited the effects of corticosterone on both the collagen type I to type III mRNA ratio and diastolic function without affecting the decrease in LV mass. Spironolactone attenuated both the increase in NADPH oxidase activity in the left ventricle and coronary vascular inflammatory responses apparent in the corticosterone group. These results indicate that exogenous glucocorticoids induce hypertension, cardiac remodeling, and diastolic dysfunction in adrenalectomized DS rats fed a high-salt diet. The cardiac effects of exogenous glucocorticoids are likely attributable, at least in part, to myocardial oxidative stress and coronary vascular inflammation induced by glucocorticoid activated MRs. PMID- 25129994 TI - Unexpected ovarian malignancy found after laparoscopic surgery in patients with adnexal masses--a single institutional experience. AB - Laparoscopy has become the standard surgery for the treatment of benign ovarian tumors. The aim of this study was to evaluate the appropriateness of laparoscopy for ovarian tumors, including those with malignant potential. A total of 487 patients with adnexal masses underwent laparoscopic surgery in Social Insurance Chukyo Hospital from January 2000 to December 2012. We reviewed 471 cases that fulfilled the criteria set for this study, and examined 10 cases with unexpected ovarian malignancy to analyze their preoperative diagnosis, second surgery, postoperative chemotherapy, and prognosis. The ages of the 471 patients ranged from 13 to 50 years, with a median of 31. Nulliparous patients numbered 321(68.1%). Of all, 436 patients mostly consisted of those with endometrioma, benign ovarian neoplasm or functional cyst. In all, we histologically identified 10 women with malignancy: 6 with borderline ovarian tumors (BOT), 2 with ovarian cancer, and 2 with histologically rare tumors (immature teratoma and granulosa cell tumor). All patients with BOT were diagnosed with a mucinous histology. Two patients underwent both second radical surgery (hysterectomy and contra- or bilateral salpingo-oophorectomy) and chemotherapies that consisted of CBDCA and PTX or DTX. Thus, 2 patients underwent staging procedures, but the remaining 8 cases did not. None of them had evidence of recurrences. With accurate staging and careful postoperative follow-up, laparoscopic surgery could be a feasible initial operation for patients with adnexal masses including early-stage ovarian malignancy. PMID- 25129995 TI - External beam radiotherapy for painful bone metastases from hepatocellular carcinoma: multiple fractions compared with an 8-Gy single fraction. AB - External beam radiotherapy (EBRT) for hepatocellular carcinoma (HCC) bone metastases has not been popular in palliative therapy, and optimum dose schedules have not been decided because of limited published reports. We here evaluated the palliative effect of EBRT for HCC bone metastases and compared the dose-response relationship between multiple fractions (MFs) and an 8-Gy single fraction (SF). Twenty-eight patients (42 sites) with painful bone metastases who received EBRT and were analyzed retrospectively. Eight patients (12 sites) received SF. Of the remaining 20 patients (30 sites), 10 received MFs at moderate doses (20-30 Gy; 17 sites) and 10 received MFs at high doses (36-52 Gy; 13 sites). Overall response was achieved at 83% (35) of all sites; 75% (9) and 87% (26) for the SF and MF patients (88%, moderate dose; 85%, high dose), respectively. No significant differences in overall response were observed between each fraction schedule. Response duration was significantly longer for the high-dose MF patients than for the SF patients and moderate-dose MF patients (P < 0.05). SF was as effective as MF radiotherapy in terms of pain relief, but high-dose MF delivery relieved pain for a significantly longer duration. PMID- 25129996 TI - The results of volar locking plate fixation for the fragility fracture population with distal radius fracture in Japanese women. AB - The purpose of this study was to determine whether volar locking plate fixation for distal radius fracture benefits the fragility fracture population as much as it benefits the non-fragility fracture population. This matched case-control study was conducted based on a multi-center clinical prospective cohort. A comparison of treatment outcomes after volar locking plate fixation was made between females 55 years of age and older (fragility fracture population) and males less than 75 years of age (non-fragility fracture population) by evaluating clinical, radiological, and subjective outcomes using Hand20, a validated patient rated disability instrument. A total of 170 patients were enrolled in this study. The two cohorts were matched in terms of AO fracture type. The fragility fracture population group and the non-fragility fracture population group each consisted of 50 patients. All objective measurements including wrist range of motion and radiological evaluations, but excluding grip strength, were not significantly different between the two groups. However, the Hand20 at 18 months after surgery was worse in the fragility fracture population group than in the non-fragility fracture population group. Carpal tunnel syndrome was the most frequently encountered complication in the fragility fracture population group, with one case (2%) in the non-fragility fracture population group and six cases (12%) in the fragility fracture population group, but the difference was not significant. In conclusion, there was a significant deficit in the improvement in disability despite favorable radiological and functional outcomes in fragility fracture population patients. Therefore, the fragility fracture population, especially middle-aged or older women, needs to be informed about prolonged disability and the higher risk of upper extremity disorders prior to surgery. PMID- 25129997 TI - Polymorphisms of Nrf2, an antioxidative gene, are associated with blood pressure in Japanese. AB - Nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor that regulates the expression of antioxidant genes by activating Nrf2 antioxidant response element (ARE) pathway. This study aimed to investigate association of Nrf2 gene single nucleotide polymorphisms (SNPs), rs35652124 (A - > G) and rs6721961 (C --> A), with various laboratory data in 464 health evaluation examinees. The genotyping of these SNPs was performed using polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay. The genotype frequencies of rs35652124 SNP were 21.1% for AA, 44.0% for AG, and 34.9% for GG. The frequency of A allele was 0.431. In male subjects, cholinesterase was significantly high, and HDL cholesterol was significantly low in (AG+GG) carriers. In female subjects, diastolic blood pressure (BP) was significantly low in (AG+GG) carriers. The genotype frequencies of rs6721961 SNP were 55.2% for CC, 34.7% for CA, and 10.1% for AA. The frequency of A allele was 0.275. In male subjects, systolic BP, diastolic BP and cholinesterase were significantly low, and iron was significantly high in (CA+AA) carriers. In female subjects, cholinesterase was significantly high in (CA+AA) carriers, and diastolic BP was significantly high in AA carriers. In conclusion, Nrf2 polymorphisms are associated with BP in Japanese. PMID- 25129998 TI - A long-term follow-up of patients with retinopathy of prematurity treated with photocoagulation and cryotherapy. AB - To evaluate the refractive characteristics of adults diagnosed with retinopathy of prematurity (ROP) treated with ablation treatment as children, we measured best corrected visual acuity (BCVA, logMAR), spherical equivalent refraction (SER), axial length (AL), lens thickness (LT), anterior chamber depth (ACD) and the corneal curvature radius (CCR) from 46 eyes, 24 patients (15-30 years old) that were diagnosed with ROP. Patients were divided into two groups dependent on the size of the treated retina at the time of ablation treatment; i.e., 360 degrees group (treatment over the whole circumference of the retina; n = 18) and partial group (treatment over part of the retina; n = 28). The study showed that LT was significantly larger (P < 1x10(-4)) and ACD was significantly shorter (P < 1 x 10(-3)) in 360 degrees group (4.26 +/- 0.40 mm and 2.92 +/- 0.48 mm, respectively) than those in partial group (3.71 +/- 0.34 mm and 3.42 +/- 0.26 mm, respectively). However, there were no differences in SER (-6.52 +/- 3.54 diopter vs. -5.95 +/- 4.12 diopter, P = 0.31), AL (23.9 +/- 1.42 mm vs. 25.0 +/- 21.48 mm, P = 0.08) and CCR (7.59 +/- 0.37 mm vs. 7.59 +/- 0.19 mm, P = 0.86). These results indicated that the eyes in the 360 degrees group had larger LTs but did not have extended ALs compared with the partial group. PMID- 25129999 TI - Factors associated with early postpartum maternity blues and depression tendency among Japanese mothers with full-term healthy infants. AB - Maternity blues and postpartum depression are common mental health problems during the early postpartum period. However, few studies have examined the factors associated with maternity blues and postpartum depression in healthy mothers with spontaneous births of healthy full-term infants. This study aimed to determine the demographic and obstetric factors, various feelings during pregnancy, and psychological factors by using the Maternity Blues Scale (MBS) and Edinburgh Postnatal Depression scale (EPDS) among healthy Japanese mothers. We distributed the MBS and EPDS self-administered questionnaires to 100 Japanese mothers during their 4-5 day hospitalization and at a health check-up 1-month after delivery, respectively. Multiple regression analyses were performed including the above-mentioned variables as independent variables and the maximum MBS or EPDS scores as dependent variables. The answers "Having a friend I can talk to about maternity life or child rearing" [beta (95% confidence interval) = 1.53 (-2.68 - -0.378)] and "Satogaeri bunben", a Japanese traditional support system wherein a postnatal woman lives with her husband/parents [-2.82 (-4.73 - 0.898)] were significantly associated with MBS scores. The answer "Having a friend I can talk to about maternity life or child rearing" [-2.83 (-4.76 - 0.903)] was also significantly associated with EPDS scores, although the association between the partner's age and these scores was marginally significant [-0.106 (-0.008 - 0.221)]. This study shows that it is important to provide support for healthy women without delivery complications, both at home and in the community. PMID- 25130000 TI - Biochemical staging of the chronic hepatic lesions of Wilson disease. AB - BACKGROUND: Copper toxicity steadily affects the livers of patients with Wilson disease. However, the toxic effect of copper on serum aspartate and alanine aminotransferase levels remains to be clarified as a prerequisite for diagnostic tests. The clinical records of 33 cases were analyzed to clarify the natural history of Wilson disease. Phenotypes were simplified into hepatic, acute, and neurologic. The bio-low stage of both enzymes was less than 40 IU/L, the bio moderate stage was intermediate between 40 and 200 IU/L, and the bio-high stage was more than 200 IU/L of either or both enzymes. Rebounded enzyme levels at the recovery period from anemia were presumed to be the chronic baselines when pre anemic enzyme levels were not available in the acute phenotype. We investigated whether these enzyme levels may provide information useful for screening patients. The natural history of chronic Wilson disease consisted of the first increasing and second decreasing phases. The clinical courses of a 4-year-old boy and 12-year-old girl were representative of the 2 phases, respectively. All but one patient were in the decreasing phase. Negative correlations were obtained between age and enzyme level in the decreasing phase. The hepatic phenotype may be a prototype found throughout the 2 phases, and acute and neurologic phenotypes may be major complications in the bio-moderate and bio-low stages of the decreasing phase, respectively. Biochemical staging may provide a better understanding of Wilson disease when combined with phenotypes. Bio-high stage patients should be referred to a medical center for diagnosis. PMID- 25130001 TI - Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite for mesothelial carcinogenesis. AB - Asbestos was abundantly used in industry during the last century. Currently, asbestos confers a heavy social burden due to an increasing number of patients with malignant mesothelioma (MM), which develops after a long incubation period. Many studies have been conducted on the effects of the asbestos types that were most commonly used for commercial applications. However, there are few studies describing the effects of the less common types, or minor asbestos. We performed a rat carcinogenesis study using Japanese tremolite and Afghan anthophyllite. Whereas more than 50% of tremolite fibers had a diameter of < 500 nm, only a small fraction of anthophyllite fibers had a diameter of < 500 nm. We intraperitoneally injected 1 or 10 mg of asbestos into F1 Fischer-344/Brown Norway rats. In half of the animals, repeated intraperitoneal injections of nitrilotriacetate (NTA), an iron chelator to promote Fenton reaction, were performed to evaluate the potential involvement of iron overload. Tremolite induced MM with a high incidence (96% with 10 mg; 52% with 1 mg), and males were more susceptible than females. Histology was confirmed using immunohistochemistry, and most MMs were characterized as the sarcomatoid or biphasic subtype. Unexpectedly NTA showed an inhibitory effect in females. In contrast, anthophyllite induced no MM after an observation period of 550 days. The results suggest that the carcinogenicity of anthophyllite is weaker than formerly reported, whereas that of tremolite is as potent as major asbestos as compared with our previous data. PMID- 25130002 TI - Dimensions of women's empowerment and their influence on the utilization of maternal health services in an Egyptian village: a multivariate analysis. AB - This study investigated the association between women's empowerment and the utilization of maternal health services by women in Egypt and analyzed the dimensions of women's empowerment that are associated with increased health service utilization. A cross-sectional survey was conducted in a village in Egypt in November 2007. A total of 189 women, who had ever been married and had at least one child, were interviewed to collect data on the utilization of maternal health services, such as the number of antenatal care (ANC) visits during their pregnancies and whether delivery of their child was attended by skilled health personnel. Proxy variables on five different dimensions of women's empowerment were obtained by principal component analysis, and were tested for an association with the utilization of maternal health services, using logistic regression models. The five dimensions extracted from the data were freedom of movement, economic security and stability, support by family and freedom from domination, decision-making in daily life, and relationship with the community/participation in society. Among these dimensions, support by family and freedom from domination was the only factor that was positively associated with maternal health service utilization (regular ANC: OR = 1.38, P = 0.05; deliveries assisted by skilled health personnel: OR = 1.71, P = 0.01). Current age was also associated with the latter, possibly influenced by the recent rapid increase in the provision of health services in the village studied. Furthermore, this study revealed that a relatively high proportion of younger women still only limited access to maternal health services in Egypt. PMID- 25130004 TI - Human laryngitis caused by Clinostomum complanatum. AB - A 64-year-old Japanese man visited our outpatient department complaining of an irritable sensation in the throat, occurring two days after eating raw freshwater fish (carp sashimi) at a Japanese-style inn. During laryngeal endoscopy, a slow moving worm (fluke) was found attached to the surface of the right aryepiglottic fold. After inhalation of 4% lidocaine, the fluke was removed using endoscopic forceps. Patient's throat symptoms immediately improved. The worm was microscopically identified as Clinostomum complanatum. C. complanatum is a digenetic trematode that usually infects fish-eating water birds. Clinostomum infections in humans are rare, and only 21 cases have been described in Japan and Korea. C. complanatum infection is known to occur after eating raw freshwater fish, which is a secondary intermediate host. In humans, the metacercariae are released into the stomach and migrate through the esophagus before lodging in the throat. Primary therapy involves endoscopic removal of the worm. PMID- 25130003 TI - Multidisciplinary management of small cell carcinoma of the breast: a case report. AB - We report a case of primary small cell carcinoma (SCC) of the breast in a 59-year old female. To the best of our knowledge, there are only 44 cases of this disease reported in the English literature. The patient also had regional nodal metastases, but no distant metastases. She underwent neoadjuvant chemotherapy according to a regimen of pulmonary SCC, and combination of cisplatin and etoposide (CDDP+VP16). The tumor partially responded to neoadjuvant chemotherapy. The treatment was followed by modified radical mastectomy and adjuvant chemotherapy, i.e., EC therapy (epirubicin and cyclophosphamide). She was also administered in total 50 Gy of radiation treatment to the chest wall. At this writing, the patient has evidenced no recurrence 36 months after her diagnosis. PMID- 25130006 TI - Chronic spontaneous lumbar epidural hematoma simulating extradural spinal tumor: a case report. AB - Spinal epidural hematoma (SEH) is an uncommon disorder, and chronic SEHs are rarer than acute SEHs. However, there is few reported involving the bone change of the vertebral body in chronic SEHs. We present a case report of lumbar epidural hematoma that required differentiation from extramedullary spinal tumors by a long process because the CT scan revealed scalloping of the vertebral body and review the relevant literature. A 78-year-old man had experienced a gradual onset of low back pain and excruciating pain in both legs. Lumbar MRI on T1 weighted images revealed a space-occupying lesion with a hyperintense signal relative to the spinal cord with no enhancement on gadolinium adminisration. Meanwhile, T2-weighted images revealed a heterogeneous intensity change, accompanying a central area of hyperintense signals with a hypointense peripheral border at the L4 vertebra. Moreover, the CT scan demonstrated scalloping of the posterior wall of the L4 vertebral body which is generally suspected as the CT finding of spainal tumor. During the epidural space exploration, we found a dark red-colored mass surrounded by a capsular layer, which was fibrous and adhered to the flavum and dura mater. Microscopic histological examination of the resected mass revealed a mixture of the relatively new hematoma and the hematoma that was moving into the connective tissue. Accordingly, the hematoma was diagnosed as chronic SEH. The particular MRI findings of chronic SEHs are helpful for making accurate preoperative diagnoses of this pathology. PMID- 25130005 TI - Gamma knife radiosurgery of brain metastasis from malignant pleural mesothelioma- report of three cases with autopsy study in a case. AB - The median survival time of malignant pleural mesothelioma (MPM) has been 9 months. Given the short survival, there have been only few cases in which brain metastases have been diagnosed and treated before death. Three cases of brain metastases treated by gamma knife radiosurgery (GKR) are reported. Case I showed a metastatic lesion in the right frontal lobe which was treated by GKR two years after diagnosis of MPM. The lesion markedly reduced and the symptoms were improved, But the patient died of progression of pleural tumor four months after GKR. A year and three months after the diagnosis, asymptomatic bifrontal lesions were treated with GKR. However, Case 2 died of abdominal mass a month after. Case 3 showed headache one and half year after the diagnosis. Three brain lesions were treated by GKR, which disappeared in 4 months. The patient died of new multiple brain metastases and periventricular dissemination seven months after. The autopsy revealed a MPM occupying the left pleural cavity. No neoplastic lesion was found in gamma knife-treated sites. The cause of death was the mass effect by new metastatic lesions. GKR was found effective also for the treatment of brain metastasis of MPM. PMID- 25130007 TI - Intraoperative migration of the trial femoral head into the pelvis during total hip arthroplasty--report of two cases. AB - Various complications occur during total hip arthroplasty (THA). It is common to implement trial treatments of various implants during THA. Here we report on 2 cases in which the trial femoral head fell into the pelvis and migrated during THA. The trial head was not retrieved but left inside in one case, while the other presented the opportunity for a possible retrieval. It is important to recognize the existence of such rare complications. PMID- 25130008 TI - Partial necrosis of the lunate after a translunate palmar perilunate fracture dislocation. AB - We present an extreme rare case of traumatic partial avascular necrosis of the lunate after palmar perilunate dislocation with lunate fracture. A 32-year-old female was injured by motorcycle accident with palmar perilunate fracture dislocation and lunate fracture. Scapholunate and lunotriquetrum dislocations were reduced and fixed temporarily. The torn dorsal ligament was repaired. Considering close observation with both arthroscopy and fluoroscopy, we decided not to conduct open reduction and internal fixation for the lunate. Partial avascular necrosis of the lunate appeared gradually in follow-up. PMID- 25130009 TI - Recurrence of solitary fibrous tumor of the cervical spinal cord. AB - Solitary fibrous tumor (SFT) mostly originates from the pleura because of proliferation of fibroblast cells. It is extremely rare for the tumor to originate from the spinal cord. Here, we report a rare case of SFT in the spinal cord that recurred repeatedly and progressed from intramedullary to extramedullary. A 40-year-old man underwent C4-5 intramedullary and extramedullary tumor resection in another hospital. Eighteen years later, he experienced symptoms of myelopathy because of tumor recurrence; therefore, he consulted with our hospital and underwent tumor resection again. During surgery, we found that the tumor had an intramedullary and extramedullary location. Only partial resection was possible because of intraoperative deterioration in the compound motor action potential (CMAP). After resection, the pathological diagnosis was SFT. The postoperative course was good. However, two years later, a third tumor resection was required because of dysuria and tumor growth. In this surgery, total resection of the tumor was possible without intraoperative deterioration of the CMAP. The tumor has not subsequently recurred. However, SFT recurrence is relatively common and careful follow-up is required for early detection of recurrence, even after successful removal of the tumor. PMID- 25130011 TI - Medical identity theft: prevention and reconciliation initiatives at Massachusetts General Hospital. AB - BACKGROUND: Medical identity theft refers to the misuse of another individual's identifying medical information to receive medical care. Beyond the financial burden on patients, hospitals, health insurance companies, and government insurance programs, undetected cases pose major patient safety challenges. Inaccuracies in the medical record may persist even after the theft has been identified because of restrictions imposed by patient privacy laws. Massachusetts General Hospital (MGH; Boston) has conducted initiatives to prevent medical identity theft and to better identify and respond to cases when they occur. METHODS: Since 2007, MGH has used a notification tree to standardize reporting of red flag incidents (warning signs of identity theft, such as suspicious personal identifiers or account activity). A Data Integrity Dashboard allows for tracking and reviewing of all potential incidents of medical identity theft to detect trends and targets for mitigation. An identity-checking policy, VERI-(Verify Everyone's Identity) Safe Patient Care, requires photo identification at every visit and follow-up if it is not provided. RESULTS: Data from MGH suggest that an estimated 120 duplicate medical records are created each month, 25 patient encounters are likely tied to identity theft or fraud each quarter, and 14 patients are treated under the wrong medical record number each year. As of December 2013, 80%-85% of patients were showing photo identification at appointments. CONCLUSION: Although an organization's policy changes and educational campaigns can improve detection and reconciliation of medical identity theft cases, national policies should be implemented to streamline the process of correcting errors in medical records, reduce the financial disincentive for hospitals to detect and report cases, and create a single point of entry to reduce the burden on individuals and providers to reconcile cases. PMID- 25130010 TI - A case of mediastinal embryonal carcinoma successfully treated by integrative therapy. AB - Mediastinal embryonal carcinoma is rare, and the life prognosis of this disease is assumed to be relatively short. We encountered a case of mediastinal embryonal carcinoma for which we could perform radical surgical resection. The patient was male, aged 16 years, and acutely aware of back pain. Because the pain increased during the same year, he visited a local doctor, and an expanding neoplastic lesion was detected in the right thoracic wall by computed tomography (CT). Then he was referred to our institution. Magnetic resonance imaging (MRI) showed a dumbbell type tumor (Eden type 3) at the Th7/8 level. Malignant disease was suspected, so the authors planned and performed CT-guided biopsy. The result showed that this tumor pathologically corresponded to malignant peripheral nerve sheath tumor (MPNST). Therefore, chemotherapy was considered the main treatment. After 2 courses of chemotherapy, the tumor size decreased dramatically. The authors thought that radical resection is possible if there is no intrathoracic tumor dissemination as a result of a favorable response to chemotherapy. We thus perfomed surgical resection after we confirmed by a thoracoscopic exploratory thoracotomy that there was no intrathoracic tumor dissemination. Pathological findings were consistent with an embryonal carcinoma. Both the cutting ends of the thoracic wall and the epidural lateral sides of the excised lesion were negative for tumor cells. There is no image finding from the MRI and PET-CT suggesting metastasis or recurrence in the MRI and PET-CT 18 months after surgical resection. Therefore, the long-term vital prognosis can be expected in this patient. PMID- 25130012 TI - A clinical practice agreement between pharmacists and surgeons streamlines medication management. AB - BACKGROUND: Collaborative practice agreements (CPAs), which have been widely used in ambulatory care, were applied to hospital surgical teams in a postsurgical colorectal surgery unit at Mayo Clinic Rochester (Minnesota). METHODS: The CPA allowed pharmacists the decision rights to initiate, modify, or discontinue medications in accordance with the surgical teams' practice standards, evidence based medicine, and/or institutional policies without specific request and response from the surgeon/provider. Interventions for CPA and non-CPA groups were captured from a prospectively maintained database. Admission medication reconciliation (patient medication list compared with hospital orders) was compared between CPA patients and non-CPA patients. Time-to-decision and surgical service interruptions were measured by an audit of 50 CPA interventions versus 50 non-CPA interventions. RESULTS: For the 135 CPA-eligible colorectal and general surgery patients in January-March 2011, there were 417 pharmacist interventions (3.1 per patient episode), compared with 537 for 305 non-CPA patients on a comparable surgical unit (1.8 per patient episode) (p < or = .0200). Admission medication reconciliation was completed for 135/135 (100%) of CPA patients versus 220/305 (72%) of non-CPA patients (p < or = .001). Rules-based interventions with CPA totaled 21/417 (5%) versus 221/537 (41%) without CPA (p < or = .0001). The time-to-decision (CPA versus non-CPA) was within 1 minute versus 0 to 4,320 minutes (mean, 314.2 minutes; median, 138 minutes), respectively (p = .0063). CONCLUSION: The CPA increased pharmacist interventions and increased both accuracy and efficiency in resolving medication-related problems. The CPA streamlined and improved medication management of hospitalized surgical patients. PMID- 25130013 TI - Walkrounds in practice: corrupting or enhancing a quality improvement intervention? A qualitative study. AB - BACKGROUND: Walkrounds, introduced as Leadership (or Executive) WalkRounds, are a widely advocated model for increasing leadership engagement in patient safety to improve safety culture, but evidence for their effectiveness is mixed. In the English National Health Service (NHS), hospitals have been strongly encouraged to make use of methods closely based on the walkrounds approach. A study was conducted to explore how walkrounds are used in practice and to identify variations in implementation that might mediate their impact on safety and culture. METHODS: The data, collected from 82 semistructured interviews in the English NHS, were drawn from two components of a wider study of culture and behavior around quality and safety in the English system. Analysis was based on the constant comparative method. FINDINGS: Our analysis highlights how local, pragmatic adjustments to the walkrounds approach could radically alter its character and the way in which it is received by those at the front line. The modification and expansion of walkrounds to increase the scope of knowledge produced could increase the value that executives draw from them. However, it risks replacing the main objectives of walkrounds--specific, actionable knowledge about safety issues, and a more positive safety culture and relationship between ward and board--with a form of surveillance that could alienate frontline staff and produce fallible insights. CONCLUSION: The studys findings suggest some plausible explanations for the mixed evidence for walkrounds' effectiveness in creating a safety culture. On a practical level, they point to critical questions that executives must ask themselves in practicing interventions of this nature to ensure that adaptations align rather than conflict with the intervention's model of change. PMID- 25130014 TI - Barriers and facilitators for taking action after classroom-based crew resource management training at three ICUs. AB - BACKGROUND: Given growing awareness of the crucial role of nontechnical skills in providing safe patient care, crew resource management (CRM) training is being increasingly used to improve them. Implementing the plans of action that are formulated during CRM training may constitute an important first step in the successful uptake of skills. Accordingly, understanding the factors that determine why participants do or do not carry out those plans should help improve CRM training and enhance its impact. A study was conducted to examine the impact of pretraining readiness factors and posttraining barriers and facilitators on follow-up on plans of action. METHODS: Three ICUs, each at a different nonacademic teaching hospital in The Netherlands, received two-day classroom based CRM training in 2010. During the training, new ideas for safety initiatives were documented as concrete plans of action. All plans were categorized as individual (for example, "Always ask a colleague to double-check your medication"), team, or organizational. Two months before and three months after the CRM training, all ICU employees were asked to fill out a set of questionnaires. RESULTS: Management support for patient safety before the training was a positive determinant of the number of perceived facilitators. A significant relationship was found between the perceived barriers and facilitators after CRM training and Taking Action. More barriers were negatively associated, while more facilitators were positively associated, with Taking Action. When assessed separately, none of the readiness factors were significantly associated with taking action, while when assessed together, the readiness factors were positive related to Taking Action. DISCUSSION: To overcome the barriers and profit from the facilitators, they should be considered during the training and in regular CRM meetings afterward. PMID- 25130015 TI - Improving the quality of care and communication during patient transitions: best practices for urgent care centers. AB - BACKGROUND: Although high-quality care transitions require timely and accurate communication of clinical information between providers, such communication is inconsistent, and there are few established guidelines outside the hospital setting. METHODS: Using a systematic, collaborative quality improvement process, Healthcentric Advisors (Providence, Rhode Island) undertook a multistage approach to define best practices for care transitions in the urgent care setting. This approach entailed review of the medical literature to identify processes that improve care transitions outcomes, gathering of information about clinicians' preferences, and a statewide community meeting with urgent care clinicians and other stakeholders to vet draft guidelines and obtain consensus on the concepts. RESULTS: Because of an inability to identify any guidelines or research that globally addressed care transitions from the urgent care setting, information was gathered from studies on patient discharge instructions and extrapolated from the evidence base available for related settings. The resulting set of eight best practices for urgent care center transitions focuses on clinician-to-clinician communication and patient activation, which can be implemented to establish measurable, communitywide expectations for communication. CONCLUSION: This set of best practices constitutes the first known guidelines to establish expectations and measures tailored specifically to transitions from the urgent care setting to the emergency department or primary care office. They can serve as a resource and a framework for urgent care clinicians expanding their collaboration with community partners, such as emergency departments and primary care providers, particularly in the context of emerging payment models. PMID- 25130016 TI - A medication-based trigger tool to identify adverse events in pediatric anesthesiology. PMID- 25130017 TI - A situational analysis of priority disaster hazards in Uganda: findings from a hazard and vulnerability analysis. AB - BACKGROUND: Most countries in sub-Saharan Africa have not conducted a disaster risk analysis. Hazards and vulnerability analyses provide vital information that can be used for development of risk reduction and disaster response plans. The purpose of this study was to rank disaster hazards for Uganda, as a basis for identifying the priority hazards to guide disaster management planning. METHODS: The study as conducted in Uganda, as part of a multi-country assessment. A hazard, vulnerability and capacity analysis was conducted in a focus group discussion of 7 experts representing key stakeholder agencies in disaster management in Uganda. A simple ranking method was used to rank the probability of occurance of 11 top hazards, their potential impact and the level vulnerability of people and infrastructure. RESULTS: In-terms of likelihood of occurance and potential impact, the top ranked disaster hazards in Uganda are: 1) Epidemics of infectious diseases, 2) Drought/famine, 3) Conflict and environmental degradation in that order. In terms of vulnerability, the top priority hazards to which people and infrastructure were vulnerable were: 1) Conflicts, 2) Epidemics, 3) Drought/famine and, 4) Environmental degradation in that order. Poverty, gender, lack of information, and lack of resilience measures were some of the factors promoting vulnerability to disasters. CONCLUSION: As Uganda develops a disaster risk reduction and response plan, it ought to prioritize epidemics of infectious diseases, drought/famine, conflics and environmental degradation as the priority disaster hazards. PMID- 25130018 TI - Institutional frameworks for management of epizoonotic emergencies in six countries in the Eastern Africa region: a situational analysis. AB - INTRODUCTION: The Eastern Africa region is a hot-spot for epidemics of emerging zoonotic diseases ('epizoonotics'). However, the region's capacity for response to epidemics of zoonotic origin has not been documented. This paper presents a multi-country situational analysis on the institutional frameworks for management of zoonotic epidemics in the Eastern Africa region. METHODS: A multi-country assessment of 6 country teams was conducted (Uganda, Kenya, Tanzania, Ethiopia, DRC and Rwanda). It involved a review of records and interviews with key informants from agencies with a stake in the management of zoonotic and disasters in general in the respective countries. Qualitative data were analyzed for key emerging themes. FINDINGS: There are many socio-cultural risk factors to epidemic prone zoonotic diseases in the region. Countries have varying levels of preparedness for zoonotic emergencies. All 6 countries have a framework for disaster management. However, technical response to epidemics is managed by the line sectors, with limited Inter-sectoral collaboration. Some sectors were disproportionately more prepared than others. Surveillance systems are mostly passive and inadequate for early detection. All 6 countries have built reasonable capacity to respond to avian influenza, but not other zoonotic emergencies. Most countries lack personnel at the operational levels, and veterinary public health services are ill-facilitated. CONCLUSION: There is need to strengthen veterinary public health services at all levels, but with a 'one health' approach. There is also need to establish 'risk-based surveillance' hot spots for zoonotic epidemics and to build community resilience 'epizoonotic' diseases. PMID- 25130019 TI - A descriptive overview of the burden, distribution and characteristics of epidemics in Uganda. AB - BACKGROUND: Although Uganda is a high burden country for epidemics of infectious diseases, the pattern of epidemics has not yet been adequately documented. The purpose of this study was to describe the distribution, magnitude and characteristics of recent epidemics in Uganda, as a basis for informing policy on priorities for targeted prevention of epidemics. METHODS: Qualitative and quantitative data was collected from the Epidemiological Surveillance Division of the Ministry of Health and the African Field Epidemiology Network through key informant interviews and a documents review. RESULTS: Acute outbreaks that have occurred since 2002 are: Cholera, Meningitis, Malaria, Viral Hemorrhagic Fevers (Ebola, Marburg), arboviruses (yellow-fever), Anthrax, Hepatitis E, Measles, Polio, Influenza A viruses, dysentery and other diarrheal diseases. Chronic outbreaks include: Propagated epidemics of cholera, head nodding disease, Hepatitis B, Hepatitis E, HIV and Typhoid Fever. Thirty-one districts had a high incidence of cholera. Most of the epidemic prone diseases are preventable through appropriate behavior change and sanitation measures. However, current focus is mainly on prevention, low focus on prevention. Community involvement in resilience and early detection is inadequate. CONCLUSION: Uganda has a high burden of preventable epidemic prone diseases. There is need to invest in surveillance, early detection and sustainable prevention through appropriate technology and behavior change involving individuals, families, communities and policy makers. PMID- 25130020 TI - Opportunities for strategic use of e-learning in scaling up disaster management capacity in Eastern Africa: a descriptive analysis. AB - BACKGROUND: The growing need for disaster management skills at all levels in Eastern Africa requires innovative approaches to training planners at all levels. While information technology tools provide a viable option, few studies have assessed the capacity for training institutions to use technology for cascading disaster management skills. METHODS: The design was an explorative survey. A pre training survey was conducted among 16 faculty members (9 academic staff and 7 information technology (IT) staff) from 7 schools of public health in Eastern Africa. Key informant interviews with 4 students and 4 staff members were conducted at the school of public health in Makerere. IT staff also conducted observations on trends of use of information technology infrastructure. RESULTS: Current levels of use of ICT among teaching and IT staff is variable. On-site use of the internet is high, but off-site access is low. Personal computers, e-mail, discussion forums and other web-based learning management platforms and open education resources (OERs) have been variably used by faculty and students to facilitate learning. On the other hand, videos, web-conferencing, social media, web-based document management tools, and mobile telephone applications were much less frequently used. A disaster management short course produced by the Health Emergencies Management Project (HEMP) has been adapted to a web-based open education resource and an interactive CD-ROM. Challenges included low levels of awareness and skills in technology options among students and faculty and access to reliable internet. CONCLUSIONS: Despite the existing challenges, technology tools are a viable platform for cascading disaster management skills in Eastern Africa. PMID- 25130022 TI - Achievements and challenges of resource allocation for health in a decentralized system in Tanzania: perspectives of national and district level officers. AB - OBJECTIVE: The goal of this study was to identify the achievements and challenges of a resource allocation process in a decentralized health system in Tanzania as they are perceived by national and district level officers. METHODOLOGY: This study was conducted between May 2011 and July 2012 in two districts of Dodoma region: Kongwa and Bahi. Data were collected from 25 key people involved in policy, planning and management aspects for the allocation of financial resources from the central government to local government districts. Thus, the recruitment of the study participants was purposive, as it took account of their positions and experience in health resource allocation and management. The data were collected through conversation in face-to-face in-depth interviews with the officers concerned. The data were analysed manually using qualitative content analysis. RESULTS: The study has identified the achievements and challenges of resource allocation in a decentralized health system of Tanzania. The achievements include: the design and use of a needs-based resource allocation formula; reduced resource allocation inequalities between rural and urban districts; and a wide discretion by the district council to mobilize and utilize health insurance funds and user fees. On the other hand, the challenges are: the disbursed funds fall far short of centrally determined budget ceilings, and the funds are sent late; Council Health Management Teams (CHMT) develop budgets but are restricted on the percentage they can allocate to different areas--so there is severe under-funding of disease prevention and health promotion initiatives at the community level. CONCLUSION: This study has identified achievements that should be further nurtured and challenges that should be worked on for the improvement of the decentralized health system. Thus, as a way forward, it is recommended that the equitable allocation of resources should go beyond the recurrent costs for the delivery of health services. PMID- 25130021 TI - Hazard analysis of Arid and semi-Arid (ASAL) regions of Kenya. AB - INTRODUCTION: This paper describes a situationanalysis on hazards in the Arid and semi-Arid lands of Kenya. The leading hazards affecting the Arid and semi-arid lands are mainly natural and include among others drought, floods, and landslides. Other hazards of importance were found to be war and conflict, HIV/AIDS and fires. Over 80% of these are weather related. OBJECTIVES: The overall objective of this study was to prioritize hazards in the ASAL region. Specifically, the study identified the top ten hazards in the ASAL Districts of Kenya, determined Probability of occurrence; Analyzed the potential impact of the hazard and utilizing multiplier effect prioritized the Hazards using a hypothetical model. METHODOLOGY: This was a descriptive study conducted in over half of the Kenya's ASAL Districts in four regions of Lower and Upper Eastern, North Eastern and part of the Coast region. Six Districts were purposively selected per region with six officers from each District all totaling one hundred and forty four. The sectors where respondents were sourced from were Agriculture, Health, local Government, and Provincial Administration, Environment and NGO. The members through a consensus process analyzed hazards in groups of their respective districts using a tool that had been developed and respondents trained on its use. RESULTS: One hundred and forty four (144) officers from Twenty four Districts in the four regions were recruited. One hundred twenty seven (81%) were male and only 27 (19% ) were female The representation of participants per sector was Governance 25% followed by Civil society organizations 21%, Health 16%, Agriculture and arid lands 15%, Research and scientific institutions 13%. The top Priority Hazards identified using the mean score were Drought and famine (5.4) Epidemics and epizootics (3.8), HIV/AIDS (3.6), War and conflict (2.5), Floods (2.5) CONCLUSIONS: The exercise confirmed the priority hazards in the Arid and semi-arid regions of Kenya and described vulnerability factors that included water scarcity, poverty and low educational levels. The region suffers from a variety of hazards in particular Drought and famine, Epidemics including HIV/AIDS and War and conflict. Environmental degradation though given a low score may be more of a perception. There is need to undertake a comprehensive hazard and Vulnerability analysis at regional and country level to inform interventions and other developmental activities. Women should be targeted at the community and leadership level, and efforts to empower them should be stepped up. PMID- 25130023 TI - Prioritization of disasters and their management in Rwanda. AB - INTRODUCTION: Rwanda has been experiencing quite a significant number of disastrous events of both natural and man-made origin in the last 2 decades. Many cases of disasters are particularly linked to the geographic, historical and socio-cultural aspects of the country. The overall objective of the present article is to perform a situation analysis of disasters in Rwanda and to highlight the institutional and legal framework of disaster management. METHODS: An assessment questionnaire focused on the current capacity, institutional frameworks and on-going initiatives for disaster management at country level and operational level was administered. The assessment was descriptive and used mainly qualitative methods. These included review of records (country policies and policy briefs, programme documents), interviews with key informants from line ministries, and interviews with key informants from stakeholder agencies. RESULTS: The Rwandan hazard profile, its vulnerability and capacity assessment shows top seven disasters which are related to epidemics, hails storms/floods; roads accidents; environmental degradation and earthquakes/volcanic eruption. Currently, the Institutional framework for disaster management and response is coordinated by Ministry of Disaster Management and Refugee Affairs through the Rwanda National Disasters Operation Center. Although disaster risk reduction has been integrated into sustainable policies and plans, most districts do not have adequate capacity to plan for disasters and the majority of districts disaster committees have not yet been trained. CONCLUSION: Rwanda has established a legal and institutional framework for disasters management. There is a need to build capacity in disaster management at operational level (District). PMID- 25130024 TI - Use of the Automated Disaster and Emergency Planning Tool in developing district level public health emergency operating procedures in three East African countries. AB - BACKGROUND: Sub-Saharan Africa is vulnerable to several natural and man-made disasters. We used the CDC Automated Disaster and Emergency Planning Tool (ADEPT) to develop all-hazards disaster management plans at district level in three eastern African countries. METHODS: During July 2008-February 2011, we used the automated disaster and emergency planning tool to conduct training on disaster planning and management in the three east African countries namely Kenya, Tanzania and Uganda. We trained district disaster teams per country. We held 7 trainings in Tanzania, 8 in Uganda and 10 in Kenya respectively. The district disaster management teams trained comprised five district administrative personnel and a national Red Cross officer. The training took 5 days. RESULTS: A total of 100 districts teams (40 in Uganda and 35 in Kenya and Tanzania respectively) were trained using the ADEPT and consequently 100 district disaster response plans were developed during 2008-2011. A total 814 district disaster team members from these districts were trained. Our experience has shown that the Automated Disaster Emergency Planning Tool is a relatively quick, easy, practical, participatory and inexpensive approach to developing emergency operating plans at the sub-national (district) level. CONCLUSIONS: The ADEPT can be used relatively easily, quickly and inexpensively at the sub-national levels to develop emergency operating procedures to improve disaster management. Although the ADEPT enables district disaster response teams to generate their disaster response plans, the use of the ADEPT may be hampered by lack of computer skills and knowledge of MS computer programme by district personnel in resource limited settings. PMID- 25130025 TI - Regional approach to building operational level capacity for disaster planning: the case of the Eastern Africa region. AB - BACKGROUND: The Eastern Africa region is regularly affected by a variety of disasters ranging from drought, to human conflict and population displacement. The magnitude of emergencies and response capacities is similar across the region. In order to strengthen public health disaster management capacities at the operational level in six countries of the Eastern Africa region, the USAID funded leadership project worked through the HEALTH Alliance, a network of seven schools of public health from six countries in the region to train district-level teams. OBJECTIVES: To develop a sustainable regional approach to building operational level capacity for disaster planning. METHODS: This project was implemented through a higher education leadership initiative. Project activities were spear-headed by a network of Deans and Directors of public health schools within local universities in the Eastern Africa region. The leadership team envisioned a district-oriented systems change strategy. Pre-service and in service curricula were developed regionally and district teams were formed to attend short training courses. Project activities began with a situational analysis of the disaster management capacity at national and operational levels. The next steps were chronologically the formation of country training teams and training of trainers, the development of a regional disaster management training curriculum and training materials, the cascading of training activities in the region, and the incorporation of emerging issues into the training curriculum. An evaluation model included the analysis of preparedness impact of the training program. RESULTS: The output from the district teams was the creation of individual district-level disaster plans and their implementation. This 4-year project focused on building operational level public health emergency response capacity, which had not previously been part of any national program. Use of the all-hazard approach rather than a scenario-based contingency planning led to the development of a standardized curriculum for training both in-service and pre service personnel. Materials developed during the implementation phases of the project have been incorporated into public health graduate curricula in the seven schools. This systems-based strategy resulted in demonstrable outcomes related to district preparedness and university engagement in disaster management. CONCLUSION: University partnerships are an effective method to build district level disaster planning capacity. Use of a regional network created a standardized approach across six countries. PMID- 25130026 TI - Performance of district disaster management teams after undergoing an operational level planners' training in Uganda. AB - INTRODUCTION: Uganda is vulnerable to several natural, man-made and a hybrid of disasters including drought, famine, floods, warfare, and disease outbreaks. We assessed the district disaster team's performance, roles and experiences following the training. FINDINGS: The disasters most commonly experienced by the district teams were epidemics of diseases in humans (7 of 12), animals (epizoonotics) (3 of 12) and crops (3 of 12); hailstorms and floods (3 of 12). The capabilities viewed most useful for management of disasters were provision of health care services (9/12) and response management (8 of 12). The capability domains most often consulted during the disasters were general response management (31%), health services (29%) and water and sanitation (17%). The skills areas perceived to be vital following the training were response to epidemics 10/12, disaster management planning 8/12, hazards and vulnerability analysis 7/12 and principles of disaster planning 7/12 respectively. Main challenges mentioned by district teams were inadequacy of finance and logistics, lack of commitment by key partners towards disaster preparedness and response. CONCLUSIONS: The most common disaster experienced disasters related to outbreaks of diseases in man, animals and crops. The most frequently applied capabilities were response management and provision of emergency health services. The activities most frequently implemented following disaster management teams training were conducting planning meetings, refinement of plans and dissemination of skills gained. The main challenges were related to limited budget allocations and legal frameworks for disaster management that should be addressed by both central and local governments. PMID- 25130027 TI - A descriptive analysis of the institutional frameworks for disaster management in Uganda: structures, functions and gaps. AB - BACKGROUND: There is insufficient documentation of the institutional frameworks for disaster management and resilience at different levels in sub-Saharan Africa. The objective of this study was to describe the institutional framework for disaster management in Uganda, and to identify actionable gaps at the different levels. METHODS: This was part of a multi-country assessment in which 6 countries in Eastern Africa developed and applied a common tool. The assessment was qualitative in nature employing a mixed methods approach including review of documents, interviews with key informants from agencies involved in disaster management in Uganda, group discussions with stakeholder and synthesis meetings of the assessment team. FINDINGS: The Office of the Prime Minister is the lead agency for disaster management, but management of disasters of a technical nature is devolved to line ministries (e.g. epidemics by the Health Ministry and Epizootics by the Agriculture Ministry). A new policy spells out disaster management structures at national, district, sub-county, and village levels. Key challenges included coordination, more focus on prevention than risk reduction, differences in capacity between sectors and inadequate inter-sectoral collaboration. The new policy and structures have not yet been rolled out to districts and sub-district levels, and districts lack a line item budget for disaster capacity building. CONCLUSIONS: The institutional framework for disaster management in Uganda needs to be strengthened at all levels through initiation of the relevant structures, training, and resource allocation so that they develop disaster management plans. PMID- 25130028 TI - Challenges towards realization of health care sector goals of Tanzania development vision 2025: training and deployment of graduate human resource for health. AB - BACKGROUND: Human resource for health (HRH) is an essential building block for effective and efficient health care system. In Tanzania this component is faced by many challenges which in synergy with others make the health care system inefficient. In vision 2025 the country recognizes the importance of the health care sector in attaining quality livelihood for its citizens. The vision is in its 13th year since its launch. Given the central role of HRH in attainment of this vision, how the HRH is trained and deployed deserves a deeper understanding. OBJECTIVE: To analyze the factors affecting training and deployment process of graduate level HRH of three core cadres; Medical Doctors, Doctor of Dental Surgery and Bachelor of Pharmacy towards realization of development vision 2025. METHODS: Explorative study design in five training institutions for health and Ministry of Health and Social Welfare (MoHSW) headquarters utilizing in-depth interviews, observations and review of available documents methodology. RESULTS: The training Institutions which are cornerstone for HRH training are understaffed, underfunded (donor dependent), have low admitting capacities and lack co-ordination with other key stakeholders dealing with health. The deployment of graduate level HRH is affected by; limited budget, decision on deployment handled by another ministry rather than MoHSW, competition between health care sector and other sectors and lack of co-ordination between employer, trainers and other key health care sector stakeholders. Awareness on vision 2025 is low in the training institutions. CONCLUSIONS: For the vision 2025 health care sector goals to be realized well devised strategies on raising its awareness in the training institutions is recommended. Quality livelihood as stated in vision 2025 will be a forgotten dream if the challenges facing the training and deployment of graduate level HRH will not be addressed timely. It is the authors' view that reduction of donor dependency syndrome, extension of retirement age for academic Staffs in the training institutions for health and synergizing the training and deployment of the graduate level HRH can be among the initial strategies towards addressing these challenges. PMID- 25130029 TI - A retrospective study on the unseen epidemic of road traffic injuries and deaths due to accidents in Mwanza City - Tanzania. AB - BACKGROUNDS: Sixty percent of the global deaths and injuries occur in the developing world and mostly are due to Road traffic accidents (RTAs. looking at the etiological related factors which include, carelessness of the driver, condition of the vehicle or motorcycle, poor condition of roads, risky behavior of the driver, most of these factors can be prevented to some extent. This study therefore, determined the pattern of cases and deaths due to traffic road accidents in Mwanza City Tanzania. METHODS: In this retrospective study, records, registers and case notes In the surgical ward and causality, medical records and central police station from 2008 to 2011 were used. The study focused on the two referral hospitals (Sekouture regional hospital and Bugando Medical Center). RESULTS: There were 3450 cases due to accidents reported at both centers (Sekouture regional hospital and Bugando Medical Center of which 3224 (93.4%) had complete information for analysis.2225 (69%) were male and 999 (31%) were female, and the most affected group were male. Among the RTAs2809 cases (87%) were due to motor cycle accidents which were the leading cause of RTAs with case fatality rate of 5% while motor vehicle has case fatality rate of 24% which is 5 times that of motor cycle. CONCLUSION AND RECOMMENDATION: Among all RTAs the leading cause of injuries is Motor cycle traffic accidents followed by motor vehicle. RTAs are on increase particularly the motor cycle traffic accidents and has claimed a good number of innocent people's lives however most of them are preventable, therefore driving course to be introduced to motor cycle drivers with emphasize on the road posters signal, rules and regular checkup of their motor cycles especially commercial motor cycle. PMID- 25130031 TI - [Dietary recommendations for chronic kidney disease, 2014]. PMID- 25130030 TI - [Classification of Diabetic Nephropathy 2014]. AB - The Committee on Diabetic Nephropathy revised the classification of diabetic nephropathy in view of the current status of eGFR and CKD in Japan. To make revisions for the classification of diabetic nephropathy 2014, the Committee carefully evaluated the report of the Research Group on Diabetic Nephropathy, Ministry of Health, Labour, and Welfare of Japan. The major revisions made were as follows: 1. eGFR can be used for the evaluation of GFR; 2. In stage 3 (overt nephropathy), A and B were combined; 3. Stage 4 (renal failure) was defined as GFR less than 30 mL/min/1.73 m2, regardless of albuminuria; and 4. The importance of differential diagnosis was stressed in all stages. PMID- 25130032 TI - [A case of glomerulopathy associated with the vascular endothelial growth factor inhibitor bevacizumab]. AB - The patient was a 73-year-old Japanese female diagnosed with stage IIIc primary peritoneal cancer. After undergoing total hysterectomy and bilateral oophorectomy, she received regimens consisting of paclitaxel (PTX) and carboplatin (CBDCA). She subsequently developed recurrence four years after the disease onset and was treated with PTX, CBDCA and the vascular endothelial growth factor (VEGF) inhibitor bevacizumab (Bev). Although clinical remission was maintained with the administration of Bev monotherapy every three weeks, proteinuria was detected six months later, and gradually increased. The findings of a renal biopsy showed diffuse wrinkling and double contouring of the glomerular tufts under light microscopy, although no immune complex deposition was observed on immunostaining. Additionally, electron microscopy showed hypertrophy of glomerular endothelial cells and widening of the subendothelial spaces. These histopathological findings were fully consistent with those of reported patients treated with VEGF inhibitors. The proteinuria attenuated following the initiation of treatment with losartan. Therefore, the administration of renoprotective therapy contributed to the patient's ability to continue the anticancer regimen with Bev in this case. PMID- 25130033 TI - [A case of atypical hemolytic uremic syndrome successfully weaned from plasma exchange by treatment with eculizumab]. AB - The patient was a 48-year-old man hospitalized for jaundice and anemia after a 6 day history of diarrhea. Examination demonstrated hemolytic anemia, renal dysfunction, and thrombocytopenia. Typical hemolytic uremic syndrome (HUS) was suspected based on the preceding colitis; however, plasma exchange (PE) was performed because the possibility of atypical HUS (aHUS) could not be ignored, given that the patient was an adult male. After 4 days of PE, his laboratory results improved. Stool culture on admission yielded negative results for Escherichia coli serotype O157 and ADAMTS13 activity. Antinuclear antibodies were normal, and no other drugs or infections indicating HUS were detected. Four months after onset, he suffered recurrence of aHUS after colitis. As a result, aHUS was suspected and therefore, PE was performed on the day of hospitalization. We diagnosed aHUS due to a result indicating complement dysregulation on hemolytic assay testing, which detected a complement factor H abnormality. After undergoing PE and maintaining a stable condition, the interval between PEs was extended; however, on day 17 after the last PE, he suffered a recurrent aHUS attack again. He could not be weaned from PE and started showing an allergic reaction to PE treatment, thereby leading to a switch from PE to eculizumab. Since switching to eculizumab treatment, the patient has not experienced another aHUS attack and his condition remains stable. PMID- 25130034 TI - [A case of thrombotic microangiopathy with glomerular subendothelial IgA deposition due to bevacizumab]. AB - Bevacizumab, an inhibitor of vascular endothelial growth factor, is approved for the treatment of various cancers, but the incidence of proteinuria as a side effect has been reported to be 2-64%. We report a case of renal impairment due to thrombotic microangiopathy (TMA) accompanied with glomerular subendothelial deposition of IgA resulting from bevacizumab administration. A 57-year-old female with advanced breast cancer, to whom bevacizumab had been administered from October 2012, developed proteinuria and epithelial casts in her urine about a month later. Serum creatinine remained at 0.7-0.8 mg/dL until June 2013, but gradually increased to 1.3 mg/dL in September. She was referred to our hospital because her renal function had not improved despite termination of bevacizumab, and a renal biopsy was performed in October. At that time, the levels of proteinuria, serum creatinine and serum IgA were high at 1.3 g/g x Cr, 1.6 mg/dL and 430 mg/dL, respectively. Histological examinations showed prominent IgA deposits in the subendothelial area and glomerular infiltration of CD68 positive cells in addition to features of TMA, such as narrowed glomerular capillary lumina and double contours of the basement membranes. In consideration of her clinical history, a diagnosis of bevacizumab-induced TMA was made. Through follow up care without readministration of bevacizumab, epithelial casts in her urine disappeared, and proteinuria decreased to 0.62 g/g x Cr in November. Serum creatinine remains high at around 1.3 mg/dL, but has not elevated further. Serum IgA gradually decreased and reached 289 mg/dL in April 2014. TMA due to bevacizumab described in several other reports was also accompanied by glomerular IgA deposition, thus a differential diagnosis of IgA nephropathy is required. TMA was recently added to a section of "significant adverse effects" in the package insert of bevacizumab. Nephrologists should be fully aware of this drug-induced nephropathy. PMID- 25130035 TI - Foreword. Recent developments in the regulation of kinins. PMID- 25130036 TI - Preface. Recent developments in the regulation of kinins. PMID- 25130037 TI - Basic and clinical aspects of bradykinin receptor antagonists. AB - Bradykinin and related kinins may act on two types of receptors designated as B1 and B2. It seems that the B2 receptors are most commonly found in various vascular and non-vascular smooth muscles, whereas B1 receptors are formed in vitro during trauma, and injury, and are found in bone tissues. These bradykinin (BK) receptors are involved in the regulation of various physiological and pathological processes. The mode of kinin actions are based upon the interactions between the kinin and their specific receptors, which can lead to activation of several second-messenger systems. Recently, numerous BK receptor antagonists have been synthesized with prime aim to treat diseases caused by excessive kinin production. These diseases are rheumatoid arthritis (RA), inflammatory diseases of the bowel, asthma, rhinitis and sore throat, allergic reactions, pain, inflammatory skin disorders, endotoxic and anaphylactic shock and coronary heart diseases. On the other hand, BK receptor antagonists could be contraindicated in hypertension, since these drugs may antagonize the antihypertensive therapy and/ or may trigger the hypertensive crisis. It is worth suggesting that the BK receptor agonists might be useful antihypertensive drugs. PMID- 25130038 TI - The kallikrein-kinin pathways in hypertension and diabetes. AB - Cardiovascular diseases are the most common causes of mortality worldwide. Hypertension and diabetes are the two major risk factors in the development of cardiac hypertrophy, ischemic heart disease, and cardiac failure. In Kuwait, high rate of prevalence of hypertension and diabetes has been documented. Previous studies have indicated altered activities of the BK-generating components in hypertension and diabetes. Bradykinin is pharmacologically active polypeptide that can promote both cardiovascular and renal function, for example, vasodilation, natriuresis, diuresis, and release of nitric oxide (NO). In addition, B2 kinin receptors are present in the cardiac endothelial cells which may enhance the biosynthesis and release of NO. It has been demonstrated that reduced urinary (renal) kallikrein levels may be associated with the development of high blood pressure in humans and spontaneously hypertensive and diabetic rats. The BK may produce its pharmacological effects via NO and cyclic GMP release. Furthermore, it is established that the BK has cardioprotective actions in myocardial ischemia and can prevent left ventricular hypertrophy. Also, transgenic mice carrying tissue kallikrein gene and overexpressing tissue kallikrein had reduced blood pressure. NO synthase and renal tissue kallikrein are both involved in blood pressure regulation. The ability of kallikrein gene delivery and the use of kinin B2 receptor agonists to produce a wide spectrum of beneficial effects make it a powerful candidate in treating hypertension, cardiovascular, and renal diseases. Strategies that activate kinin receptors might be applicable to the treatment of cardiovascular disease. Increased plasma prekallikrein levels in diabetic patients may serve as an indicator of developing hypertension and renal damage. Also high plasma and urine concentrations of tissue kallikrein may cause higher glucose levels in the blood. PMID- 25130039 TI - Tissue kallikrein-kinin therapy in hypertension and organ damage. AB - Tissue kallikrein is a serine proteinase that cleaves low molecular weight kininogen to produce kinin peptides, which in turn activate kinin receptors to trigger multiple biological functions. In addition to its kinin-releasing activity, tissue kallikrein directly interacts with the kinin B2 receptor, protease-activated receptor-1, and gamma-epithelial Na channel. The tissue kallikrein-kinin system (KKS) elicits a wide spectrum of biological activities, including reducing hypertension, cardiac and renal damage, restenosis, ischemic stroke, and skin wound injury. Both loss-of-function and gain-of-function studies have shown that the KKS plays an important endogenous role in the protection against health pathologies. Tissue kallikrein/kinin treatment attenuates cardiovascular, renal, and brain injury by inhibiting oxidative stress, apoptosis, inflammation, hypertrophy, and fibrosis and promoting angiogenesis and neurogenesis. Approaches that augment tissue kallikrein-kinin activity might provide an effective strategy for the treatment of hypertension and associated organ damage. PMID- 25130041 TI - The kallikrein-kinin system in diabetic retinopathy. AB - Diabetic retinopathy (DR) is a major microvascular complication associated with type 1 and type 2 diabetes mellitus, which can lead to visual impairment and blindness. Current treatment strategies for DR are mostly limited to laser therapies, steroids, and anti-VEGF agents, which are often associated with unwanted side effects leading to further complications. Recent evidence suggests that kinins play a primary role in the development of DR through enhanced vascular permeability, leukocytes infiltration, and other inflammatory mechanisms. These deleterious effects are mediated by kinin B1 and B2 receptors, which are expressed in diabetic human and rodent retina. Importantly, kinin B1 receptor is virtually absent in sane tissue, yet it is induced and upregulated in diabetic retina. These peptides belong to the kallikrein-kinin system (KKS), which contains two separate and independent pathways of regulated serine proteases, namely plasma kallikrein (PK) and tissue kallikrein (TK) that are involved in the biosynthesis of bradykinin (BK) and kallidin (Lys-BK), respectively. Hence, ocular inhibition of kallikreins or antagonism of kinin receptors offers new therapeutic avenues in the treatment and management of DR. Herein, we present an overview of the principal features and known inflammatory mechanisms associated with DR along with the current therapeutic approaches and put special emphasis on the KKS as a new and promising therapeutic target due to its link with key pathways directly associated with the development of DR. PMID- 25130040 TI - Renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs for salt-sensitive hypertension. AB - A large variety of antihypertensive drugs, such as angiotensin converting enzyme inhibitors, diuretics, and others, are prescribed to hypertensive patients, with good control of the condition. In addition, all individuals are generally believed to be salt sensitive and, thus, severe restriction of salt intake is recommended to all. Nevertheless, the physiological defense mechanisms in the kidney against excess salt intake have not been well clarified. The present review article demonstrated that the renal (tissue) kallikrein-kinin system (KKS) is ideally situated within the nephrons of the kidney, where it functions to inhibit the reabsorption of NaCl through the activation of bradykinin (BK)-B2 receptors localized along the epithelial cells of the collecting ducts (CD). Kinins generated in the CD are immediately inactivated by two kidney-specific kinin-inactivating enzymes (kininases), carboxypeptidase Y-like exopeptidase (CPY), and neutral endopeptidase (NEP). Our work demonstrated that ebelactone B and poststatin are selective inhibitors of these kininases. The reduced secretion of the urinary kallikrein is linked to the development of salt-sensitive hypertension, whereas potassium ions and ATP-sensitive potassium channel blockers ameliorate salt-sensitive hypertension by accelerating the release of renal kallikrein. On the other hand, ebelactone B and poststatin prolong the life of kinins in the CD after excess salt intake, thereby leading to the augmentation of natriuresis and diuresis, and the ensuing suppression of salt-sensitive hypertension. In conclusion, accelerators of the renal kallikrein release and selective renal kininase inhibitors are both novel types of antihypertensive agents that may be useful for treatment of salt-sensitive hypertension. PMID- 25130042 TI - Genetic manipulation and genetic variation of the kallikrein-kinin system: impact on cardiovascular and renal diseases. AB - Genetic manipulation of the kallikrein-kinin system (KKS) in mice, with either gain or loss of function, and study of human genetic variability in KKS components which has been well documented at the phenotypic and genomic level, have allowed recognizing the physiological role of KKS in health and in disease. This role has been especially documented in the cardiovascular system and the kidney. Kinins are produced at slow rate in most organs in resting condition and/or inactivated quickly. Yet the KKS is involved in arterial function and in renal tubular function. In several pathological situations, kinin production increases, kinin receptor synthesis is upregulated, and kinins play an important role, whether beneficial or detrimental, in disease outcome. In the setting of ischemic, diabetic or hemodynamic aggression, kinin release by tissue kallikrein protects against organ damage, through B2 and/or B1 bradykinin receptor activation, depending on organ and disease. This has been well documented for the ischemic or diabetic heart, kidney and skeletal muscle, where KKS activity reduces oxidative stress, limits necrosis or fibrosis and promotes angiogenesis. On the other hand, in some pathological situations where plasma prekallikrein is inappropriately activated, excess kinin release in local or systemic circulation is detrimental, through oedema or hypotension. Putative therapeutic application of these clinical and experimental findings through current pharmacological development is discussed in the chapter. PMID- 25130043 TI - Increased transfusion-free survival following auxiliary pig liver xenotransplantation. AB - BACKGROUND: Pig to baboon liver xenotransplantation typically results in severe thrombocytopenia and coagulation disturbances, culminating in death from hemorrhage within 9 days, in spite of continuous transfusions. We studied the contribution of anticoagulant production and clotting pathway deficiencies to fatal bleeding in baboon recipients of porcine livers. METHODS: By transplanting liver xenografts from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) miniature swine donors into baboons as auxiliary organs, leaving the native liver in place, we provided the full spectrum of primate clotting factors and allowed in vivo mixing of porcine and primate coagulation systems. RESULTS: Recipients of auxiliary liver xenografts develop severe thrombocytopenia, comparable to recipients of conventional orthotopic liver xenografts and consistent with hepatic xenograft sequestration. However, baboons with both pig and native livers do not exhibit clinical signs of bleeding and maintain stable blood counts without transfusion for up to 8 consecutive days post-transplantation. Instead, recipients of auxiliary liver xenografts undergo graft failure or die of sepsis, associated with thrombotic microangiopathy in the xenograft, but not the native liver. CONCLUSION: Our data indicate that massive hemorrhage in the setting of liver xenotransplantation might be avoided by supplementation with primate clotting components. However, coagulation competent hepatic xenograft recipients may be predisposed to graft loss related to small vessel thrombosis and ischemic necrosis. PMID- 25130044 TI - Altered expression of 3beta-HSD, CYP17 and 17beta-HSD in the foetal porcine gonads in response to anti-androgen flutamide exposure. AB - We investigated whether the limited access to androgens during late prenatal period alters expression of steroidogenic enzymes involved in androgen production: 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (3beta HSD), cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) and 17beta hydroxysteroid dehydrogenase type 1 (17beta-HSD1) or type 3 (17beta-HSD3) in the foetal porcine gonads. Pregnant gilts were injected with anti-androgen flutamide (for seven days, 50 mg/day/kg bw) or corn oil (control) starting at 83 (GD90) or 101 (GD108) gestational day. To assess 3beta-HSD, CYP17 and 17beta-HSD1 or 17beta HSD3 expression, real-time PCR and immunohistochemistry were performed. In testes from flutamide-treated foetuses, increased 3beta-HSD and CYP17 mRNA expression was observed in the GD90 group, while decreased 3beta-HSD and 17beta-HSD3 mRNA expression and increased CYP17 mRNA expression were found in the GD108 group. CYP17 and 17beta-HSD3 were localized in Leydig cells. Following flutamide administration, the intensity of CYP17 immunostaining was higher in both treated groups, while 17beta-HSD3 intensity was lower in the GD108 group. In ovaries from flutamide-treated foetuses in the GD90 group, mRNA level for 3beta-HSD was elevated, but it was diminished for CYP17 and 17beta-HSD1. In the GD108 group, flutamide treatment led to lower mRNA level for 3beta-HSD but higher for CYP17. 3beta-HSD was found in granulosa cells, while CYP17 was localized within egg nests and oocytes of forming follicles. Following flutamide treatment, the intensity of 3beta-HSD and CYP17 immunostaining was higher in the GD90 and GD108 groups, respectively. Immunohistochemical staining for 3beta-HSD was restricted to the ovary. Concluding, diminished androgen action in the porcine foetal gonads during late gestation induces changes in steroidogenic enzymes expression, which may led to changes in gonadal function. However, it seems that androgens exert diverse biological effects depending on the gestational period. PMID- 25130045 TI - Comparison of the results of intradermal test reactivity and serum allergen specific IgE measurement for Malassezia pachydermatis in atopic dogs. AB - BACKGROUND: Malassezia pachydermatis is part of the normal flora of canine skin. Malassezia hypersensitivity is recognized as a trigger for clinical signs of atopic dermatitis (AD) in some dogs. Determinations of Malassezia hypersensitivity are often made with intradermal testing (IDT), which may have limited availability in a first-opinion veterinary practice. HYPOTHESIS/OBJECTIVES: The purpose of this study was to compare immediate IDT reactivity to M. pachydermatis with results of an enzyme-linked immunosorbent assay (ELISA) designed to detect anti-Malassezia IgE. ANIMALS: Eighty-four dogs with a clinical diagnosis of AD. METHODS: Multi-allergen IDT was performed on all dogs. Serum testing for allergen-specific IgE against a panel of common environmental allergens and M. pachydermatis was performed by ELISA using the FcepsilonRIalpha receptor fragment as a detection reagent, with results reported as adjusted optical density (OD). A receiver operating characteristic (ROC) curve was used to analyse the results of the two tests. RESULTS: The median adjusted OD of the anti-Malassezia IgE ELISA for dogs reactive and nonreactive to M. pachydermatis on IDT was 0.137 and 0.024, respectively. Analysis of the ROC curve suggested a cut-off point for the anti-Malassezia ELISA that yielded a sensitivity of 77.0% and a specificity of 89% relative to IDT results. CONCLUSIONS AND CLINICAL IMPORTANCE: Substantial agreement was demonstrated between IDT reactivity and anti-Malassezia IgE as detected by the FcepsilonRIalpha receptor reagent. Although correlation with a clinical diagnosis of Malassezia dermatitis was not attempted in this study, the results indicate that the ELISA may be used to demonstrate the presence of immediate-type Malassezia hypersensitivity in dogs with AD. PMID- 25130046 TI - Practitioner Review: Diagnosing childhood resilience--a systemic approach to the diagnosis of adaptation in adverse social and physical ecologies. AB - BACKGROUND: With growing interest in resilience among mental health care providers globally, there is a need for a simple way to consider the complex interactions that predict adaptive coping when there is exposure to high levels of adversity such as family violence, mental illness of a child or caregiver, natural disasters, social marginalization, or political conflict. METHODS: This article presents diagnostic criteria for assessing childhood resilience in a way that is sensitive to the systemic factors that influence a child's wellbeing. The most important characteristics of children who cope well under adversity and avoid problems like depression, PTSD, and delinquency are highlighted. RESULTS: A multidimensional assessment of resilience is presented that examines, first, the severity, chronicity, ecological level, children's attributions of causality, and cultural and contextual relevance of experiences of adversity. Second, promotive and protective factors related to resilience are assessed with sensitivity to the differential impact these have on outcomes depending on a child's level of exposure to adversity. These factors include individual qualities like temperament, personality, and cognitions, as well as contextual dimensions of positive functioning related to the available and accessibility of resources, their strategic use, positive reinforcement by a child's significant others, and the adaptive capacity of the environment itself. Third, an assessment of resilience includes temporal and cultural factors that increase or decrease the influence of protective factors. A decision tree for the diagnosis of resilience is presented, followed by a case study and diagnosis of a 15-year-old boy who required treatment for a number of mental health challenges. CONCLUSIONS: The diagnostic criteria for assessing resilience and its application to clinical practice demonstrate the potential usefulness of a systemic approach to understanding resilience among child populations. PMID- 25130047 TI - Management of children with possible appendicitis: a survey of emergency physicians in Australia and New Zealand. AB - OBJECTIVES: To describe current practice in managing children with possible acute appendicitis in EDs in Australia and New Zealand as the basis for a clinical practice guideline (CPG). METHODS: An anonymous survey was distributed to consultant emergency physicians working at PREDICT (Paediatric Research in Emergency Departments International Collaborative) sites in Australia and New Zealand in April 2013. A second, site-based survey was distributed to the PREDICT representatives at each of the 13 sites. RESULTS: The response rate was 100% (13/13) for the site-based survey and 82% (145/176) for the physician survey. Most respondents agreed that right lower quadrant (RLQ) tenderness (94%), anorexia (92%), migration of abdominal pain to the RLQ (86%), rebound tenderness in the RLQ (60%) and RLQ tenderness produced on coughing, hopping or percussion (63%) were valuable symptoms and signs in diagnosing appendicitis. The responses regarding nausea and vomiting and fever were less consistent. Less than 50% regarded blood tests (C-reactive protein, white cell count) as relevant for the diagnosis of appendicitis. Most physicians (61%) agreed there was a role for a validated CPG for possible appendicitis in children, although only 3/13 sites reported use of such a CPG. CONCLUSIONS: This survey of senior emergency physicians across Australia and New Zealand demonstrated congruence in several clinical markers and disagreements in others in the approach to diagnosing children with possible appendicitis. Whereas emergency physicians would like a validated CPG, this survey has highlighted some critical issues. Particularly, the low regard for blood tests, integral to published diagnostic scoring systems, will be a challenge for the development and introduction of such a CPG in Australia and New Zealand. PMID- 25130048 TI - The effect of trait type and strength of selection on heritability and evolvability in an island bird population. AB - The heritability (h(2) ) of fitness traits is often low. Although this has been attributed to directional selection having eroded genetic variation in direct proportion to the strength of selection, heritability does not necessarily reflect a trait's additive genetic variance and evolutionary potential ("evolvability"). Recent studies suggest that the low h(2) of fitness traits in wild populations is caused not by a paucity of additive genetic variance (VA ) but by greater environmental or nonadditive genetic variance (VR ). We examined the relationship between h(2) and variance-standardized selection intensities (i or betasigma ), and between evolvability (IA :VA divided by squared phenotypic trait mean) and mean-standardized selection gradients (betaMU ). Using 24 years of data from an island population of Savannah sparrows, we show that, across diverse traits, h(2) declines with the strength of selection, whereas IA and IR (VR divided by squared trait mean) are independent of the strength of selection. Within trait types (morphological, reproductive, life-history), h(2) , IA , and IR are all independent of the strength of selection. This indicates that certain traits have low heritability because of increased residual variance due to the age at which they are expressed or the multiple factors influencing their expression, rather than their association with fitness. PMID- 25130049 TI - Evidence-based guidelines for laboratory screening for infectious diseases before initiation of systemic immunosuppressive agents in patients with autoimmune bullous dermatoses. AB - Autoimmune bullous dermatoses (ABD) compromise the skin's innate barrier function for preventing infection. Treating patients with ABD frequently requires systemic immunosuppressive therapy, often with multiple agents. Currently, no pretreatment infection testing guidelines are available for clinicians caring for patients with ABD. We performed a systematic literature review in other medical disciplines that use similar iatrogenic immunosuppressive medications to treat various diseases and conditions and developed infection-testing recommendations for patients with ABD before initiating immunosuppressive therapy. Assessing individual patient risk factors for latent infection and preventable communicable diseases can direct testing for select infections before starting immunosuppressive therapy. Testing patients for hepatitis B virus, hepatitis C virus, and Mycobacterium tuberculosis infection is recommended before initiating rituximab treatment. PMID- 25130050 TI - Prevalence and risk factors for isolation of methicillin-resistant Staphylococcus in dogs with keratitis. AB - OBJECTIVE: To determine the prevalence of, and risk factors for, methicillin resistant Staphylococcus (MRS) isolation in dogs with naturally acquired bacterial keratitis. PROCEDURES: All Staphylococcus spp. isolated from corneal samples of dogs with keratitis during a 2-year period were evaluated for methicillin resistance by bacteriologic methods. Each MRS isolate was subjected to in vitro susceptibility testing for systemic and ocular antimicrobials. Nasal swabs for culture were collected from all dogs with MRS corneal isolation to evaluate for nasal carrier status. Potential risk factors for MRS isolation were investigated by medical record review and administration of an epidemiological survey to dog owners. Collected information characterizing animal, client, and environmental variables was analyzed for association with MRS isolation. RESULTS: Seventy-one Staphylococcus spp. were isolated from seventy individual dogs with keratitis during the study period. Seventeen of the Staphylococcus isolates (23.9%) were methicillin resistant. The MRS isolates included Staphylococcus epidermidis (n = 10), Staphylococcus pseudintermedius (n = 6), and Staphylococcus aureus (n = 1). The MRS corneal isolates displayed extensive antimicrobial resistance. Four dogs (23.5%) with MRS corneal isolates had positive nasal cultures for MRS. Client occupation was significantly (P = 0.01) associated with MRS isolation, and dogs belonging to owners employed in veterinary or human healthcare fields were four times more likely to have MRS keratitis than dogs owned by clients with different professions. There were no significant associations between the other evaluated animal, client, and environmental factors. CONCLUSIONS: Methicillin resistance is relatively common in Staphylococcus isolates from dogs with corneal infections, particularly among dogs belonging to healthcare workers. PMID- 25130051 TI - Portal blood - a new source of dendritic cells for pancreatic cancer vaccine. AB - INTRODUCTION: Cohort study evaluated dendritic cells (DCs) subsets in portal and peripheral blood of patients with pancreatic cancer (PC) and chronic pancreatitis (CHP). MATERIAL AND METHODS: Myeloid type 1 (mDCs1) and 2 (mDCs2), plasmocytoid (pDCs) and SLAN + DCs were assessed in PC (n = 20) and CHP (n = 6) patients. RESULTS: Percentage of mDCs1 was significantly lower in PC patients when compared to CHP (0.48 +/- 0.26 vs 0.76 +/- 0.3; p = 0.038) only in portal, but not peripheral blood. DISCUSSION: Further studies to assess the functional properties of portal blood DCs and their applicability in anticancer vaccination are needed. PMID- 25130053 TI - Upper limb joint kinetics of three sitting pivot wheelchair transfer techniques in individuals with spinal cord injury. AB - STUDY DESIGN: Repeated measures design. OBJECTIVE: This study compared the upper extremity (UE) joint kinetics between three transfer techniques. SETTING: Research laboratory. METHODS: Twenty individuals with spinal cord injury performed three transfer techniques from their wheelchair to a level tub bench. Two of the techniques involved a head-hips method with leading hand position close (HH-I) and far (HH-A) from the body, and the third technique with the trunk upright (TU) and hand far from body. Motion analysis equipment recorded upper body movements and force sensors recorded their hand and feet reaction forces during the transfers. RESULTS: Several significant differences were found between HH-A and HH-I and TU and HH-I transfers indicating that hand placement was a key factor influencing the UE joint kinetics. Peak resultant hand, elbow, and shoulder joint forces were significantly higher for the HH-A and TU techniques at the trailing arm (P < 0.036) and lower at the leading arm (P < 0.021), compared to the HH-I technique. CONCLUSION: Always trailing with the same arm if using HH A or TU could predispose that arm to overuse related pain and injuries. Technique training should focus on initial hand placement close to the body followed by the amount of trunk flexion needed to facilitate movement. PMID- 25130052 TI - Pharmacodynamic effects of oral oxymorphone: abuse liability, analgesic profile and direct physiologic effects in humans. AB - Oxymorphone is a semisynthetic MU-opioid agonist, marketed as a prescription analgesic purported to be twice as potent as oxycodone for pain relief. Oral formulations of oxymorphone were reintroduced in the United States in 2006 and reports of abuse ensued; however, there are limited data available on its pharmacodynamic effects. The current study aimed to examine the direct physiologic effects, relative abuse liability, analgesic profile and overall pharmacodynamic potency of oxymorphone in comparison with identical doses of oxycodone. Healthy, non-dependent opioid abusers (n = 9) were enrolled in this within-subject, double-blind, placebo-controlled, 3-week inpatient study. Seven experimental sessions (6.5 hours) were conducted, during which an oral dose of immediate-release formulations of oxymorphone (10, 20 and 40 mg), oxycodone (10, 20 and 40 mg) or placebo was administered. An array of physiologic, abuse liability and experimental pain measures was collected. At identical doses, oxymorphone produced approximately twofold less potent effects on miosis, compared with oxycodone. Oxymorphone also produced lesser magnitude effects on measures of respiratory depression, two experimental pain models and observer rated agonist effects. However, 40 mg of oxymorphone was similar to 40 mg of oxycodone on several abuse-related subjective ratings. Formal relative potency analyses were largely invalid because of the substantially greater effects of oxycodone. Overall, oxymorphone is less potent on most pharmacodynamic measures, although at higher doses, its abuse liability is similar to oxycodone. These data suggest that the published clinical equianalgesic estimates may not be consistent with the observed direct physiologic effects of opioids, results of experimental pain models or abuse liability measures, as assessed in the human laboratory. PMID- 25130056 TI - Necessary stem cell transplantation using myeloablative therapy for myelodysplastic syndrome with progression of genotypic abnormalities and TP53 dysfunction in a young adult. AB - A 14-yr-old male was admitted to our hospital with MDS and the chromosomal abnormality 45,XY,der(5;17)(p10;q10). He rapidly developed karyotype abnormalities, accompanied by the loss of tumor suppressor gene TP53 function. He suffered an early relapse after reduced-intensity-conditioning SCT and ultimately required myeloablative therapy before a second SCT. We consider that the analysis of TP53 mutations is essential when planning the treatment of patients with MDS. PMID- 25130054 TI - Assessment of respiration-induced displacement of canine abdominal organs in dorsal and ventral recumbency using multislice computed tomography. AB - Respiratory-induced organ displacement during image acquisition can produce motion artifacts and variation in spatial localization of an organ in diagnostic computed tomography (CT) examinations. The purpose of this prospective study was to quantify respiratory-induced abdominal organ displacement in dorsal and ventral recumbency using five normal dogs. All dogs underwent CT examinations using 64 multidetector row CT (64-MDCT). A "3-dimensional (3D) apneic CT exam" of the abdomen was acquired followed by a "4-dimensional (4D) ventilated CT exam." The liver, pancreas, both kidneys, both medial iliac lymph nodes, and urinary bladder were delineated on the 3D-apneic examination and the organ outlines were compared to the maximum alteration in organ position in the 4D-ventilated examination. Displacement was measured in dorsal-to-ventral (DV), right-to-left (RL), and cranial-to-caudal (CC) directions. Respiratory-induced displacement of canine abdominal organs was not predictable and showed large variability in the three directions evaluated. For most canine abdominal organs, dorsal recumbency provided overall the least amount of displacement among all directions evaluated except for liver and urinary bladder. For liver, a large variability was found for all directions and a statistically significant difference was found only in the RL direction with ventral recumbency exhibiting less displacement (P = 0.0099). For the urinary bladder, ventral recumbency also provided less displacement but this was statistically significant only in the RL direction (P < 0.0001). Findings from this study indicated that dorsal recumbency may be preferred for minimizing respiratory motion artifacts in whole abdomen studies, but ventral recumbency may be preferred for liver and urinary bladder studies when respiration cannot be controlled. PMID- 25130057 TI - Targeted proteomics analysis of protein degradation in plant signaling on an LTQ Orbitrap mass spectrometer. AB - Targeted proteomics has become increasingly popular recently because of its ability to precisely quantify selected proteins in complex cellular backgrounds. Here, we demonstrated the utility of an LTQ-Orbitrap Velos Pro mass spectrometer in targeted parallel reaction monitoring (PRM) despite its unconventional dual ion trap configuration. We evaluated absolute specificity (>99%) and sensitivity (100 amol on column in 1 MUg of total cellular extract) using full and mass range scans as survey scans together with data-dependent (DDA) and targeted MS/MS acquisition. The instrument duty cycle was a critical parameter limiting sensitivity, necessitating peptide retention time scheduling. We assessed synthetic peptide and recombinant peptide standards to predict or experimentally determine target peptide retention times. We applied optimized PRM to protein degradation in signaling regulation, an area that is receiving increased attention in plant physiology. We quantified relative abundance of selected proteins in plants that are mutant for enzymatic components of the N-end rule degradation (NERD) pathway such as the two tRNA-arginyl-transferases ATE1 and ATE2 and the two E3 ubiquitin ligases PROTEOLYSIS1 and 6. We found a number of upregulated proteins, which might represent degradation targets. We also targeted FLAGELLIN SENSITIVE2 (FLS2), a pattern recognition receptor responsible for pathogen sensing, in ubiquitin ligase mutants to assay the attenuation of plant immunity by degradation of the receptor. PMID- 25130058 TI - Human tyrosinase is able to oxidize both enantiomers of rhododendrol. AB - Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol, RD) was used as a topical skin-whitening agent until it was recently reported to induce leukoderma. We then showed that oxidation of RD with mushroom tyrosinase rapidly produces RD-quinone, which is quickly converted to RD-cyclic quinone and RD-hydroxy-p-quinone. In this study, we examined whether either or both of the enantiomers of RD can be oxidized by human tyrosinase. Using a chiral HPLC column, racemic RD was resolved optically to R(-)-RD and S(+)-RD enantiomers. In the presence of a catalytic amount of l-dopa, human tyrosinase, which can oxidize l-tyrosine but not d tyrosine, was found to oxidize both R(-)- and S(+)-RD to give RD-catechol and its oxidation products. S(+)-RD was more effectively oxidized than l-tyrosine, while R(-)-RD was less effective. These results support the notion that the melanocyte toxicity of RD depends on its tyrosinase-catalyzed conversion to toxic quinones and the concomitant production of reactive oxygen species. PMID- 25130059 TI - Drowned, buried and carried away: effects of plant traits on the distribution of native and alien species in riparian ecosystems. AB - Riparian vegetation is exposed to stress from inundation and hydraulic disturbance, and is often rich in native and alien plant species. We describe 35 traits that enable plants to cope with riparian conditions. These include traits for tolerating or avoiding anoxia and enabling underwater photosynthesis, traits that confer resistance and resilience to hydraulic disturbance, and attributes that facilitate dispersal, such as floating propagules. This diversity of life history strategies illustrates that there are many ways of sustaining life in riparian zones, which helps to explain high riparian biodiversity. Using community assembly theory, we examine how adaptations to inundation, disturbance and dispersal shape plant community composition along key environmental gradients, and how human actions have modified communities. Dispersal-related processes seem to explain many patterns, highlighting the influence of regional processes on local species assemblages. Using alien plant invasions like an (uncontrolled) experiment in community assembly, we use an Australian and a global dataset to examine possible causes of high degrees of riparian invasion. We found that high proportions of alien species in the regional species pools have invaded riparian zones, despite not being riparian specialists, and that riparian invaders disperse in more ways, including by water and humans, than species invading other ecosystems. PMID- 25130060 TI - Intraoperative changes in blood pressure, heart rate, plasma vasopressin, and urinary noradrenalin during elective ovariohysterectomy in dogs: repeatability at removal of the 1st and 2nd ovary. AB - OBJECTIVE: To investigate the physiologic reactions after removal of 1st ovary and whether this is repeated during removal of the 2nd ovary in elective ovariohysterectomy. STUDY DESIGN: Prospective study. ANIMALS: Dogs (n = 10). METHODS: Dogs were premedicated with acepromazine, carprofen, and methadone and anesthetized with propofol and isoflurane. Blood pressure, heart rate, and end tidal isoflurane concentration were measured every minute. The effects of various events during surgery on physiologic variables were analyzed using mixed linear models. Blood and urine samples were collected before anesthesia, before incision, before and after removal of ovaries with a 15 minute pause between ovary removal, and after abdominal closure. Plasma vasopressin and urinary noradrenalin and creatinine concentrations were analyzed. RESULTS: The magnitude of blood pressure increase at removal of the 1st ovary was greater than for the 2nd ovary because of an elevation in baseline. Similarly, the heart rate increased at the removal of the 1st ovary but not at removal of the 2nd ovary. Plasma vasopressin concentration increased at removal of both ovaries. Urinary noradrenalin/creatinine ratio increased at anesthesia, removal of both ovaries, and was elevated at closure of the abdomen. End-tidal isoflurane concentration did not change. Blood pressure and vasopressin concentrations changed in parallel using z-scores for comparison. CONCLUSIONS: Peak values for blood pressure, heart rate, plasma vasopressin concentration, and urinary noradrenalin/creatinine ratio did not differ between removals of the ovaries. Relative changes differed between repeated noxious stimuli, which should be considered in evaluation of methods at ovary removal. PMID- 25130062 TI - Lithium for bipolar disorder: a review of the recent literature. AB - Lithium is a commonly prescribed treatment for bipolar disorder. Many early studies on which its use has been historically based no longer meet current research standards. A large number of studies with more modern designs have been recently published warranting a review. New research adds to the evidence for lithium's efficacy in mania and maintenance. There is also additional evidence, albeit less robust, to support its benefit in bipolar depression and mixed episodes. Meta-analyses of mainly observational data have found reduced suicidal behavior in bipolar patients taking lithium. Careful monitoring and prescribing can reduce the risk of adverse effects. PMID- 25130061 TI - Effects of lifestyle modification and metformin on irisin and FGF21 among HIV infected subjects with the metabolic syndrome. AB - OBJECTIVE: Few studies have investigated irisin and FGF21 to elucidate the role of these hormones to regulate 'beiging' in HIV-infected patients. DESIGN: Fifty HIV-infected subjects with the metabolic syndrome were previously recruited and randomized to receive lifestyle modification (LSM) and/or metformin over 12 months. In the current study, we assessed FGF21 and irisin at baseline and after intervention. In addition, we assessed circulating FGF21 and irisin in relationship to brown adipose tissue (BAT) gene expression in dorsocervical subcutaneous fat biopsies from 13 HIV-infected subjects. RESULTS: At baseline, prior to intervention, HIV-infected subjects demonstrated increased log FGF21 (2.13 +/- 0.06 vs 1.98 +/- 0.05 pg/ml, P = 0.05) and log irisin (0.33 +/- 0.02 vs 0.17 +/- 0.04 MUg/ml, P = 0.003) compared with healthy controls well matched based on waist circumference. After 12 months, HIV-infected subjects randomized to LSM demonstrated a relative reduction in FGF21 compared with those not randomized to LSM (-10 [-35,22] vs 40 [0,94] %change, P = 0.01). Changes in FGF21 were inversely associated with improved parameters of energy homoeostasis, including increased REE (rho = -0.34, P = 0.046) and max VO2 (rho = -0.38, P = 0.02), and reduced RQ (rho = 0.40, P = 0.02) among all HIV-infected subjects. Increased UCP-1 (r = 0.75, P = 0.003), DIO2 (r = 0.58, P = 0.04) and CideA (r = 0.73, P = 0.01) gene expression in dorsocervical fat was significantly associated with FGF21 in HIV-infected subjects. CONCLUSION: HIV-infected subjects with metabolic complications demonstrate increases in FGF21 in relationship to BAT gene expression. Relative reductions in FGF21 in those receiving long-term LSM relate to overall improvements in energy expenditure parameters. In contrast, irisin levels are elevated in HIV-infected subjects, but are not influenced by LSM nor associated with BAT gene expression. PMID- 25130063 TI - Acylation of ghrelin is increased in heart failure and decreases post heart transplantation. AB - OBJECTIVES: Ghrelin is an anabolic hormone that is elevated in heart failure (HF), with resistance to its anabolic effects. This resolves after heart transplantation (HTx). Ghrelin exists in acylated and des-acyl forms, with the acylated form being primarily responsible for endocrine actions. We tested the hypothesis that ghrelin derangements in HF are due to inadequate acylation and that this resolves post transplantation. DESIGN: Plasma levels of des-acyl and acylated ghrelin and acylated/total ratios were assessed in HF (n = 20), post-HTx (n = 35), and healthy controls (n = 4), and correlated with each other and with clinical parameters. RESULTS: Median (interquartile range) of des-acyl ghrelin level, was 167 (121-195) pg/ml in HF versus 149 (130-223) pg/ml in post-HTx, p = NS. Acylated ghrelin level was 76 (51-99) pg/ml versus 13 (0-30) pg/ml, p < 0.001. Acylated/total ratios were 0.33 (0.20-0.47) versus 0.08 (0-0.13), p < 0.001. The correlation between acylated and total ghrelin levels was greater in HF than that in HTx. Acyl ghrelin correlated inversely with body mass index in HF, but not in HTx. CONCLUSION: Acylated ghrelin and the acylated/total ratio were dramatically higher in HF compared with those in HTx. Acylation rather than secretion of ghrelin is upregulated in HF and the resistance to ghrelin's anabolic and appetite-stimulating effects is not at the level of acylation, but downstream at the ghrelin-receptor level. PMID- 25130064 TI - Cost analysis of the development and implementation of a spatial decision support system for malaria elimination in Solomon Islands. AB - BACKGROUND: The goal of malaria elimination faces numerous challenges. New tools are required to support the scale up of interventions and improve national malaria programme capacity to conduct detailed surveillance. This study investigates the cost factors influencing the development and implementation of a spatial decision support system (SDSS) for malaria elimination in the two elimination provinces of Isabel and Temotu, Solomon Islands. METHOD: Financial and economic costs to develop and implement a SDSS were estimated using the Solomon Islands programme's financial records. Using an ingredients approach, verified by stakeholders and operational reports, total costs for each province were quantified. A budget impact sensitivity analysis was conducted to investigate the influence of variations in standard budgetary components on the costs and to identify potential cost savings. RESULTS: A total investment of US$ 96,046 (2012 constant dollars) was required to develop and implement the SDSS in two provinces (Temotu Province US$ 49,806 and Isabel Province US$ 46,240). The single largest expense category was for computerized equipment totalling approximately US$ 30,085. Geographical reconnaissance was the most expensive phase of development and implementation, accounting for approximately 62% of total costs. Sensitivity analysis identified different cost factors between the provinces. Reduced equipment costs would deliver a budget saving of approximately 10% in Isabel Province. Combined travel costs represented the greatest influence on the total budget in the more remote Temotu Province. CONCLUSION: This study provides the first cost analysis of an operational surveillance tool used specifically for malaria elimination in the South-West Pacific. It is demonstrated that the costs of such a decision support system are driven by specialized equipment and travel expenses. Such factors should be closely scrutinized in future programme budgets to ensure maximum efficiencies are gained and available resources are allocated effectively. PMID- 25130065 TI - The mental health of unaccompanied refugee minors on arrival in the host country. AB - Despite increasing numbers of unaccompanied refugee minors (UM) in Europe and heightened concerns for this group, research on their mental health has seldom included the factor "time since arrival." As a result, our knowledge of the mental health statuses of UM at specific points in time and over periods in their resettlement trajectories in European host countries is limited. This study therefore examined the mental health of UM shortly after their arrival in Norway (n = 204) and Belgium (n = 103) through the use of self-report questionnaires (HSCL-37A, SLE, RATS, HTQ). High prevalence scores of anxiety, depression and posttraumatic stress disorder (PTSD) symptoms were found. In addition, particular associations were found with the number of traumatic events the UM reported. The results indicate that all UM have high support needs on arrival in the host country. Longitudinal studies following up patterns of continuity and change in their mental health during their trajectories in the host country are necessary. PMID- 25130066 TI - Study on accommodation by autorefraction and dynamic refraction in children. AB - PURPOSE: Childhood accommodation interferes with accurate diagnosis of the latent refractive errors. Dynamic retinoscopy offers accurate measurements of accommodative response, while an autorefractometer can predict the accommodative system activation in children. A correlation of the accommodative effort with the dynamic refraction has been investigated in emmetropic children, before and after cycloplegia. METHODS: A prospective clinical study of accommodative effort in 149 emmetropic children, in the age group 3-16 years, has been conducted using TOPCON AR RM-8000B autorefractor. Dynamic refraction was performed by monocular estimation method before and after cycloplegia, using the retinoscope mirror light as target. Retinoscopic reflex produced 'with the motion' was corrected with positive spherical lenses, and that 'against the motion' was corrected with negative spherical lenses, to achieve neutralization. RESULTS: Mean accommodative effort measured for 149 children included in the study was -0.63+/-0.69D and dynamic refraction was -0.07+/-0.44D before cycloplegia, while the mean was+0.52D after cycloplegia, irrespective of the method used. Autorefractor measured -0.17D of accommodative effort per unit change in dynamic refraction before cycloplegia and +0.90D after cycloplegia. CONCLUSIONS: The performance of TOPCON AR RM-8000B autorefractor was comparable to dynamic retinoscopy. Presence of many children, and in turn, large number of accommodative response data in 11-13 and 14-15 years group is probably linked to prolonged reading/writing. The accuracy and the agreement of the actual accommodative measurements revealed after cycloplegia. PMID- 25130067 TI - Bowman strip complications during routine LASIK: Two cases demonstrating the clinical advantage of using Mitomicyn C in such cases. PMID- 25130068 TI - Does organizational justice predict empowerment? Nurses assess their work environment. AB - PURPOSE: The purpose of the study was to explore how nurses assess their empowerment and clarify organizational justice compared to other work-related factors. In addition, we examined the major variables pertinent to empowerment. DESIGN: Cross-sectional survey data were used. METHODS: A total of 2,152 nurses returned the completed questionnaire. The instruments consisted of nurse empowerment, organizational justice, job control, and possibilities for developing work. The data analysis was based on descriptive statistics and further statistical tests. FINDINGS: Organizational justice and empowerment had a clear correlation. Job control, possibilities for developing work and organizational justice were statistically significant predictors of nurse empowerment. CONCLUSIONS: Organizational justice and the possibility to use one's individual skills at work are significant factors in staff activity and its development in nursing. They increase the level of empowerment and commitment as well as motivation to work. CLINICAL RELEVANCE: The results of this study confirm that nurses regard organizational justice as highly important. We can facilitate both work-related empowerment and organizational justice by creating and maintaining a culture of fairness and justice. Employees should be heard and involved more in the planning and decision making of work. PMID- 25130069 TI - High preoperative C-reactive protein values predict poor survival in patients on chronic hemodialysis undergoing nephrectomy for renal cancer. AB - OBJECTIVES: Previous studies have reported that elevated pretreatment C-reactive protein (CRP) levels are associated with poor outcome in various malignancies, including renal cell carcinoma (RCC), in the general population. However, there is no evidence of such an association in dialysis patients. Therefore, the aim of this study is to evaluate the prognostic significance of preoperative serum CRP levels in patients with RCC related to end-stage renal disease (ESRD) requiring hemodialysis (HD). MATERIALS AND METHODS: We evaluated 315 patients with ESRD requiring HD who underwent nephrectomy for RCC as the first-line treatment at our hospital from 1982 to 2013. Complete patient- and tumor-specific characteristics as well as preoperative CRP levels were assessed. We defined a serum CRP level >0.5mg/dl as elevated and divided these patients into 2 groups according to their preoperative CRP levels (CRP<=0.5 and >0.5mg/dl). The median follow-up was 51 months. RESULTS: Preoperative CRP levels were elevated in 75 patients (23.8%). The Kaplan-Meier 5-year cancer-specific survival rates were 95.2% and 69.9% in patients with CRP levels<=0.5 and>0.5mg/dl, respectively (P<0.0001). Multivariate analysis identified preoperative CRP level as an independent predictor for cancer specific survival, along with a pathological TNM stage and tumor grade (CRP>0.5: hazard ratio = 3.47; 95% CI: 1.35-9.18; P = 0.0098). The concordance index of multivariable base models increased after including the preoperative CRP levels. CONCLUSIONS: Preoperative serum CRP level might be an independent predictor of postoperative survival in patients with RCC related to ESRD requiring HD. Its routine use, together with the TNM classification and tumor grade, could allow better risk stratification and risk-adjusted follow-up of these patients. PMID- 25130070 TI - PEG mediated synthesis and biological evaluation of asymmetrical pyrazole curcumin analogues as potential analgesic, anti-inflammatory and antioxidant agents. AB - The new series of asymmetrical pyrazole curcumin analogues 4a-g were synthesized by using polyethylene glycol (PEG-400) as a green reaction medium and evaluated for their in vivo analgesic and in vitro antioxidant (H2 O2 , DPPH, Ferrous reducing power and Nitric oxide scavenging activity) and anti-inflammatory activities. All the compounds synthesized 4a-g showed the potential to demonstrate analgesic activity as compared to the standard ibuprofen. Among the tested series, compounds 4e and 4b exhibited good hydrogen peroxide scavenging activity as compared to the standard butylated hydroxy toluene (BHT). Compounds 4b, 4d, 4f, and 4g showed good DPPH free radical scavenging activity. Compounds 4b, 4c, 4d, 4e and 4g showed excellent ferrous-reducing power activity, whereas all the compounds showed better nitric oxide scavenging activity than standard ascorbic acid. Additionally, all the synthesized compounds were also screened for their in vitro anti-inflammatory activity. Compounds 4b, 4d, 4f and 4g showed good anti-inflammatory activity as compared to standard diclofenac sodium. PMID- 25130071 TI - Isolation of Enterococcus faecium NM113, Enterococcus faecium NM213 and Lactobacillus casei NM512 as novel probiotics with immunomodulatory properties. AB - Probiotics, defined as living bacteria that are beneficial for human health, mainly function through their immunomodulatory abilities. Hence, these microorganisms have proven successful for treating diseases resulting from immune deregulation. The aim of this study was to find novel candidates to improve on and complement current probiotic treatment strategies. Of 60 lactic acid bacterial strains that were isolated from fecal samples of healthy, full-term, breast-fed infants, three were chosen because of their ability to activate human immune cells. These candidates were then tested with regard to immunomodulatory properties, antimicrobial effects on pathogens, required pharmacological properties and their safety profiles. To identify the immunomodulatory structures of the selected isolates, activation of specific innate immune receptors was studied. The three candidates for probiotic treatment were assigned Enterococcus faecium NM113, Enterococcus faecium NM213 and Lactobacillus casei NM512. Compared with the established allergy-protective strain Lactococcus lactis G121, these isolates induced release of similar amounts of IL-12, a potent inducer of T helper 1 cells. In addition, all three neonatal isolates had antimicrobial activity against pathogens. Analysis of pharmacological suitability showed high tolerance of low pH, bile salts and pancreatic enzymes. In terms of safe application in humans, the isolates were sensitive to three antibiotics (chloramphenicol, tetracycline and erythromycin). In addition, the Enterococcus isolates were free from the four major virulence genes (cylA, agg, efaAfs and ccf). Moreover, the isolates strongly activated Toll-like receptor 2, which suggests lipopeptides as their active immunomodulatory structure. Thus, three novel bacterial strains with great potential as probiotic candidates and promising immunomodulatory properties have here been identified and characterized. PMID- 25130073 TI - Relationship between oral bacteria count and pneumonia onset in elderly nursing home residents. AB - AIM: Oral bacteria, which are a source of infection for aspiration pneumonia, were examined in frail older adults with the aim of establishing a standard bacteria count that indicates the risk of pneumonia onset in this group. METHODS: A survey of bacteria count in the saliva using a simple instrument for measurement of the number of oral bacteria, along with factors including swallowing function and nutritional status, was carried out in 691 elderly individuals requiring care (137 men; mean age 82.6 +/- 8.3 years; 554 women; mean age 88.0 +/- 7.1 years; total mean age 86.7 +/- 7.8 years) at 16 nursing homes in Japan. All participants gave their consent for inclusion in the present study. During a 6-month follow-up period, participants who developed pneumonia were identified, and relationships between the factors measured at the start of the period and pneumonia onset were examined. RESULTS: During the 6-month follow-up period, 33 participants (4.8%; 5 men, 28 women; mean age 88.3 +/- 7.4 years) developed pneumonia. Pneumonia onset was significantly associated with reduced activities of daily living, swallowing dysfunction and undernourishment. Logistic regression analysis identified a saliva bacteria count of 10(8.5) colony-forming units/mL as an independent explanatory factor for pneumonia onset (P = 0.012, RR = 3.759). CONCLUSIONS: Oral bacteria count of 10(8.5) colony-forming units/mL saliva in an elderly person requiring care was identified as a risk factor for pneumonia onset. PMID- 25130072 TI - Immune response of gammadeltaT cells in Schistosome japonicum-infected C57BL/6 mouse liver. AB - Systematic evaluation of the role of gammadeltaT cells during the Schistosoma japonicum infection has not been reported, despite the fact that gammadeltaT cells contribute to many infectious diseases in innate immunity. Therefore, the aim of this study was to observe the properties of gammadeltaT cells in the liver of C57BL/6 mice infected by S. japonicum. In this report, using immuno fluorescent histological analysis, gammadeltaT cells were found around hepatic granulomatous. Moreover, the flow cytometry results revealed that the percentage of hepatic gammadeltaT cells increased significantly after S. japonicum infection. More interestingly, a subset of CD3(-)gammadeltaTCR(+) cells were found and markedly increased after infection. Furthermore, expression of activation markers (CD25 and CD69) and cytokine profiles were detected in these hepatic CD3(+)gammadeltaTCR(+) and CD3(-)gammadeltaTCR(+) cells. The significantly higher level of CD69, IL-4 and IL-17 were observed in CD3(+)gammadeltaTCR(+) cells after infection, suggesting that CD3(+)gammadeltaTCR(+) cells instead of CD3(-)gammadeltaTCR(+) cells might play a predominant role during the infection. Finally, our results indicated that the expression of NKG2D on CD3(+)gammadeltaTCR(+) cells was higher than that on CD3( )gammadeltaTCR(+) cells. Collectively, gammadeltaT cells could play an important role in the liver of C57BL/6 mouse during japonicum infection. PMID- 25130074 TI - Modalities of fetal evaluation to detect fetal compromise prior to the development of significant neurological damage. AB - AIMS: The aim of this study was to clarify the developmental mechanism underlying fetal heart rate (FHR) long-term variability (LTV) and acceleration with respect to fetal brain damage. MATERIAL AND METHODS: The fetal state was deduced from the developmental mechanism of FHR variability analyzed by actocardiogram, animal experiments, and simulations. RESULTS: LTV develops due to minor fetal movements in the fetal midbrain, moderate LTV by fetal periodic movements and triangular accelerations by large fetal movement bursts. Stimulation of the fetal midbrain by sound and light produces fetal movements that lead to FHR acceleration. Severe hypoxia can result in the loss of LTV and neuronal necrosis that may damage the fetal brain. Therefore, a cesarean section is recommended prior to the loss of LTV, rather than after its loss. The vagal center of the fetal medulla oblongata is excited by hypoxia and produces FHR bradycardia. The heart rate of hypoxic rabbits was found to be closely correlated with the PaO2, thus the impact of hypoxia could be estimated by the hypoxia index, which is calculated from the reciprocal of nadir FHR and bradycardia duration. CONCLUSIONS: Analyzing the development of FHR signs could help to diagnose fetal state. An early cesarean section is recommended before the loss of LTV as indicated by the hypoxia index, which will contribute to prevent fetal brain damage and neurological sequels. PMID- 25130076 TI - Causes of readmission after operation for congenital heart disease. AB - BACKGROUND: Readmission after operations for congenital heart conditions has significant implications for patient care. Readmission rates vary between 8.7% and 15%. The aim of this study was to determine the incidence, causes, and risk factors associated with readmission. METHODS: 811 consecutive patients undergoing operations for congenital heart conditions were analyzed. Readmission was defined as admission to any hospital within 30 days of discharge for any cause. Demographic, preoperative, operative, and postoperative variables were evaluated. Univariate comparisons were made between the nonreadmission and readmission groups, and multivariate logistic regression analysis was made to determine independent risk factors for readmission. RESULTS: There were a total of 92 readmissions in 79 patients (9.7%). The reasons included cardiac (36, 39%), pulmonary (20, 22%), gastrointestinal (13, 14%), infectious (20, 22%), and other adverse events (2, 2%). Patients with either single-ventricle palliation or nasogastric feeding accounted for 40 (50%) readmissions. On univariate analysis, there were significant differences between readmitted and nonreadmitted patients in relation to patient age, chromosomal abnormality, mortality risk score, duration of mechanical ventilation, postoperative length of stay, single ventricle physiology, and nasogastric feeding at discharge (p < 0.05). On multivariate analysis, significant risk factors for readmission were single ventricle physiology (odds ratio [OR] 2.39; 95% confidence interval [CI] 1.28 to 4.47; p=0.005), preoperative arrhythmia (OR 2.59; 95% CI 1.02 to 6.59; p=0.04), longer postoperative length of stay (OR 2.2; 95% CI 1.22 to 3.99; p=0.008), and nasogastric tube feeding at discharge (OR 2.2; 95% CI 1.15 to 4.19; p=0.01). CONCLUSIONS: The incidence of readmission after operations for congenital cardiac conditions remains high. Efforts focusing on patients with single-ventricle palliation and those with preoperative arrhythmia, prolonged postoperative length of stay and nasogastric tube feeding at discharge may be particularly beneficial. PMID- 25130075 TI - Posterior papillary muscle anchoring affects remote myofiber stress and pump function: finite element analysis. AB - BACKGROUND: The role of posterior papillary muscle anchoring (PPMA) in the management of chronic ischemic mitral regurgitation (CIMR) is controversial. We studied the effect of anchoring point direction and relocation displacement on left ventricular (LV) regional myofiber stress and pump function. METHODS: Previously described finite element models of sheep 16 weeks after posterolateral myocardial infarction (MI) were used. True-sized mitral annuloplasty (MA) ring insertion plus different PPM anchoring techniques were simulated. Anchoring points tested included both commissures and the central anterior mitral annulus; relocation displacement varied from 10% to 40% of baseline diastolic distance from the PPM to the anchor points on the annulus. For each reconstruction scenario, myofiber stress in the MI, border zone, and remote myocardium as well as pump function were calculated. RESULTS: PPMA caused reductions in myofiber stress at end-diastole and end-systole in all regions of the left ventricle that were proportional to the relocation displacement. Although stress reduction was greatest in the MI region, it also occurred in the remote region. The maximum 40% displacement caused a slight reduction in LV pump function. However, with the correction of regurgitation by MA plus PPMA, there was an overall increase in forward stroke volume. Finally, anchoring point direction had no effect on myofiber stress or pump function. CONCLUSIONS: PPMA reduces remote myofiber stress, which is proportional to the absolute distance of relocation and independent of anchoring point. Aggressive use of PPMA techniques to reduce remote myofiber stress may accelerate reverse LV remodeling without impairing LV function. PMID- 25130077 TI - Myocardial perfusion, scarring, and function in anomalous left coronary artery from the pulmonary artery syndrome: a long-term analysis using magnetic resonance imaging. AB - BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital heart defect. We aimed to examine the role of cardiac magnetic resonance imaging (MRI) in the long-term surveillance of repaired ALCAPA with regard to myocardial scarring, wall motion abnormalities, perfusion deficits, and myocardial function. METHODS: Twenty-one patients after direct reimplantation of ALCAPA (median age at operation, 2.8 years) were examined after a median 10.6 years by MRI at rest and under dobutamine stress conditions, echocardiography, and ergometry. Results were compared with preoperative, immediately postoperative (5 days), and intermediate-term (5.8 years) echocardiography. RESULTS: No early or late deaths occurred. Improvements in indexed left ventricular end-diastolic dimension, ejection fraction, and mitral valve function were observed in all patients. However, MRI at rest showed wall motion abnormalities in 67% and perfusion deficits in 28%. Myocardial scars were seen in 67%. Dobutamine stress MRI detected wall motion abnormalities in 19% and perfusion deficits in 14%, which were not seen on MRI at rest. Exercise testing did not reflect cardiac dysfunction. CONCLUSIONS: Although long-term follow-up showed global left ventricular function had improved after ALCAPA repair, MRI showed left ventricular wall motion abnormalities, perfusion deficits, and myocardial scarring were seen in many patients. Dobutamine stress MRI identified deficits that were not evident on MRI at rest, and can therefore be considered a valuable surveillance tool. These results suggest the need for lifelong surveillance of repaired ALCAPA. PMID- 25130078 TI - Congenital cardiac lesions involving systolic flow abnormalities are associated with platelet dysfunction in children. AB - BACKGROUND: Shear stress-induced platelet dysfunction (PD) is prevalent among adults with aortic stenosis. Our aim was to determine whether abnormal platelet function was associated with specific congenital cardiac lesions in children. METHODS: The charts of 407 children who had undergone cardiopulmonary bypass and had preoperative platelet function analysis were evaluated. Patients were assigned to 1 of 11 different lesion categories. Platelet dysfunction (PD) was defined as prolonged closure time (CT) as measured with a platelet function analyzer. Odds ratio (OR) estimates for prolonged CT were calculated for each lesion category. Mean CTs were compared with Tukey-Kramer separated means testing. Analysis of variance modeling was used to determine association between hematocrit value and CT. RESULTS: CT in patients with ventricular septal defects (VSD) and right ventricular outflow tract obstruction (RVOTO) lesions was prolonged. OR analysis found that patients with VSDs (OR, 2.46) or RVOTO (OR, 2.88) had at least a 95% probability of an abnormal CT. In contrast, patients with atrial septal defect (ASD), bidirectional Glenn procedure (BDG), and pulmonary insufficiency (PI) had a reduced probability of a prolonged CT (p < 0.05). A similar pattern was seen in parametric analysis comparing mean CTs across lesion categories. A lower preoperative hematocrit value was associated with prolonged CTs across all lesion types (p < 0.05). CONCLUSIONS: PD was common in children with congenital cardiac lesions involving systolic flow abnormalities and was uncommon among children with lesions having diastolic abnormalities. Lower preoperative hematocrit values were associated with prolonged CTs, suggesting subclinical bleeding secondary to excessive platelet shearing. PMID- 25130079 TI - Impact of neonatal versus nonneonatal total repair of tetralogy of fallot on growth in the first year of life. AB - BACKGROUND: Optimal timing for total repair in tetralogy of Fallot (TOF) is controversial. We aimed to determine if weight at 1 year differs between patients who undergo neonatal total repair versus those who undergo nonneonatal total repair later in the first year of life. METHODS: A retrospective review of infants admitted with TOF between January 2004 and June 2011 was conducted. Patient data, including weight, were collected throughout the first year of life, and neonatal total repair versus nonneonatal total repair groups were compared. RESULTS: Of 163 infants, neonatal total repair was undertaken in 36 (22%) of them, whereas 127 (78%) infants had nonneonatal total repair at greater than 28 days of life. The median neonatal intensive care unit length of stay (LOS) was longer for the neonatal total repair group than for the nonneonatal total repair group (17.5 [11-24] versus 7 [0-15] days; p < 0.001). Patients in the neonatal total repair group were more likely to have a transannular patch (TAP) (p < 0.001) than were those in the nonneonatal total repair group, whereas patients in the nonneonatal total repair group were more likely to have undergone a valve sparing operation (p = 0.002). The mean weight-for-age z score was 0.7 higher in the neonatal total repair group compared with the nonneonatal total repair group (p = 0.03) controlling for birth weight (BW), diagnostic subgroup, and gestational age (GA). CONCLUSIONS: Patients with TOF who underwent neonatal total repair were more likely to receive a TAP but had higher weight-for-age scores at 1 year compared with patients who underwent full repair later in the first year of life. PMID- 25130080 TI - A half-sandwich organometallic single-ion magnet with hexamethylbenzene coordinated to the Dy(III) ion. AB - A half-sandwich organolanthanide complex, [(C6Me6)Dy(AlCl4)3], in which Dy(III) is coordinated with a pi-bonded arene was synthesized and magnetically characterized. This complex displays slow magnetic relaxation and a hysteresis loop associated with single-ion magnet behavior. The orientation of the magnetic anisotropy axis is analyzed using ab initio calculations. PMID- 25130081 TI - Prognostic role of hyponatremia in 564 small cell lung cancer patients treated with topotecan. AB - OBJECTIVES: Hyponatremia is reported in about 15% of small cell lung cancer (SCLC). Variable results of the prognostic significance of low plasmatic sodium (Napl) have been reported. Our study was performed to investigate the prognostic role of hyponatremia in SCLC patients treated in second-line with topotecan chemotherapy. MATERIALS AND METHODS: Data were retrospectively collected from a database including clinical data from 631 patients enrolled in 6 prospective topotecan iv studies. Final data were obtained from 564 patients in which data on baseline Napl were available. Univariate and multivariate analysis were carried out to study the possible correlation between Napl and second-line clinical outcomes. RESULTS: Hyponatremia (Napl<135mequiv./l) was present in 101 cases (17.9%). Napl was <125mequiv./l in 16 patients (2.8%), 126-130mequiv./l in 11 (2%), 130-134mequiv./l in 74 (13.1%), while 463 patients (82.1%) showed normal values. The median survival was 28.7 weeks in patients with normal Napl, and 21.1 weeks in patients with hyponatremia (p<0.0001, HR=1.67, 95%CI=1.32-2.10). By Cox multivariate analysis, hyponatremia was associated with poorer prognosis (p=0.0024, HR=1.44, 95%CI=1.13-1.82). A not statistically significant trend of correlation between hyponatremia and progression-free survival (p=0.085, HR=1.23, 95%CI 0.97-1.55) and response rate (p=0.5037, OR=0.81, 95%CI 0.44-1.49) was observed. CONCLUSION: Hyponatremia is an independent prognostic factor for patients with SCLC treated with topotecan in second-line setting. Further studies are needed to prospectically confirm these results and to develop an optimal therapy for hyponatremic patients. PMID- 25130082 TI - Lung cancer in the era of Greek economic crisis. PMID- 25130083 TI - Metastatic sites and survival in lung cancer. AB - OBJECTIVES: Population-based data on metastatic sites and survival in site specific metastases are lacking for lung cancer and for any cancer because most cancer registries do not record metastases. This study uses a novel population based approach to identify metastases from both death certificates and national inpatient data to describe metastatic pathways in lung cancer patients. MATERIALS AND METHODS: 17,431 deceased lung cancer patients diagnosed 2002-2010 were identified from the nationwide Swedish Cancer Registry, which is based on compulsory reports. The influence of age at diagnosis, sex, and histological subtype on metastatic spread was investigated. Survival in metastatic lung cancer was assessed by histology and metastatic site. RESULTS: The most frequent metastatic sites were the nervous system, bone, liver, respiratory system, and adrenal gland. Liver (35%) and nervous system (47%) metastases were common in patients with metastases from small cell lung cancer, and bone (39%) and respiratory system (22%) metastases in adenocarcinoma. Women (43% vs. 35%) and younger patients had more metastases to the nervous system. Median survival after diagnosis was 13 months for non-metastatic and five months for metastatic lung cancer. In this novel data, liver metastases conferred the worst prognosis (three months), especially for large cell histology. Bone metastases also featured poor survival, whereas survival in respiratory and nervous system metastases was better. CONCLUSION: Metastatic sites and survival in metastatic lung cancer is influenced by sex, histological subtype, and age at diagnosis. Liver and bone metastases signal poor survival, compared with nervous system metastases. PMID- 25130085 TI - Chiral speciation of selenoamino acids in biological samples. AB - In this paper, the "state of the art" of chiral speciation of selenoamino acids (SeAAs) in biological samples is critically reviewed. The significance and the features of such studies are highlighted. A special focus lies on chiral speciation of SeAAs by hyphenation techniques in which a chiral separation method (such as gas chromatography (GC), high performance liquid chromatography (HPLC) and capillary electrophoresis (CE)) is on-line coupled with an elemental specific detector, especially inductively coupled plasma mass spectrometry (ICP-MS). The advances in the development and application of hyphenation techniques in chiral speciation of SeAAs in biological samples are summarized and a perspective for future developments including sophisticated and innovative applications is discussed. Overall, HPLC-ICP-MS is more applicable than GC/CE-ICP-MS for chiral speciation of SeAAs. In the future, more novel chiral HPLC methods with high enantio-resolution, low cost and robustness, and their more applications in real biological samples analysis are expected. PMID- 25130084 TI - A phase II trial evaluating the clinical and immunologic response of HLA-A2(+) non-small cell lung cancer patients vaccinated with an hTERT cryptic peptide. AB - OBJECTIVES: The immunological and clinical responses of patients with NSCLC treated, in the context of an expanded action program, with the cryptic hTERT targeting Vx-001 vaccine are presented. MATERIALS AND METHODS: Forty-six HLA A*0201-positive patients with advanced NSCLC and residual (n=27) or progressive (n=19) disease following front-line treatment received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide, every 3 weeks. Peptide-specific immune responses were monitored by enzyme-linked immunosorbent spot assay at baseline, and after the 2nd and the 6th vaccinations. Thirty-eight HLA-A*0201-positive matched patients were used as historical controls. RESULTS: Twenty-three patients (50%) completed the vaccination protocol and 87% received at least two administrations. Twelve patients (26%) without disease progression after the 6th vaccination received boost vaccinations. Three (7%) patients achieved a partial response and 13 (28%) disease stabilization. The disease control rate was significantly higher in patients with non-squamous histology compared to those with squamous-cell histology [n=14 (45%) versus n=2 (13%); p=0.03]. The median progression-free survival (PFS) and overall survival (OS) was 3.8 (range, 0.7-99.4) and 19.8 months (range, 0.7-99.4), respectively. Patients who developed immune response had a numerically higher PFS compared to those who failed to mount any (6.7 versus 2.7 months; p=0.090). However, the median OS for the immune-responders was significantly prolonged compared to non-responders (40.0 versus 9.2 months, respectively; p=0.02). Toxicity was =24 kg/m2) nulliparous women, 14 developed non-proteinuric PIH and 12 developed proteinuric PIH (preeclampsia), whereas 46 had normotensive pregnancies. Insulin sensitivity was assessed via the whole-body insulin sensitivity index (ISI) and the homeostatic model of assessment - insulin resistance (HOMA-IR) at 24 weeks of gestation. Maternal serum levels of FABP4, high-sensitive C-reactive protein (hs CRP), total testosterone, and non-protein-bound calculated free testosterone (cfT) were determined at 24 and 32 weeks. RESULTS: Measures of ISI, HOMA-IR, hs CRP, testosterone and lipids did not differ at 24 and/or at 32 weeks in women who were subsequently hypertensive. SBP was higher at all time points and FABP4 levels tended to be higher at 24 and 32 weeks in patients compared to controls. In logistic regression analysis, baseline FABP4 (OR [95% CI] 1.069 [1.020-1.121], P = 0.006) and SBP after 10 min standing (OR [95% CI] 1.087 [1.029-1.149], P = 0.003) were associated with the development of PIH. FABP4 levels at 24 weeks did not correlate with insulin sensitivity. Neither was correlation seen between FABP4 levels at 24 and 32 weeks, vs. those of hs-CRP and testosterone. DISCUSSION AND CONCLUSIONS: Serum FABP4 concentration and SBP after 10 min standing in an orthostatic test at 24 weeks are associated with subsequent development of PIH. PMID- 25130096 TI - Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities. AB - With reports of pandrug-resistant bacteria causing untreatable infections, the need for new antibacterial therapies is more pressing than ever. Alkaloids are a large and structurally diverse group of compounds that have served as scaffolds for important antibacterial drugs such as metronidazole and the quinolones. In this review, we highlight other alkaloids with development potential. Natural, semisynthetic and synthetic alkaloids of all classes are considered, looking first at those with direct antibacterial activity and those with antibiotic enhancing activity. Potent examples include CJ-13,136, a novel actinomycete derived quinolone alkaloid with a minimum inhibitory concentration of 0.1 ng/mL against Helicobacter pylori, and squalamine, a polyamine alkaloid from the dogfish shark that renders Gram-negative pathogens 16- to >32-fold more susceptible to ciprofloxacin. Where available, information on toxicity, structure activity relationships, mechanisms of action and in vivo activity is presented. The effects of alkaloids on virulence gene regulatory systems such as quorum sensing and virulence factors such as sortases, adhesins and secretion systems are also described. The synthetic isoquinoline alkaloid virstatin, for example, inhibits the transcriptional regulator ToxT in Vibrio cholerae, preventing expression of cholera toxin and fimbriae and conferring in vivo protection against intestinal colonisation. The review concludes with implications and limitations of the described research and directions for future research. PMID- 25130097 TI - Human, food and animal Campylobacter spp. isolated in Portugal: high genetic diversity and antibiotic resistance rates. AB - Infections by Campylobacter jejuni and Campylobacter coli are considered the major cause of bacterial gastroenteritis in humans, with food being the main source of infection. In this study, a total of 196 Campylobacter strains (125 isolates from humans, 39 from retail food and 32 from food animal sources) isolated in Portugal between 2009 and 2012 were characterised by multilocus sequence typing (MLST) and flaA short variable region (SVR) typing. Susceptibility to six antibiotics as well as the mechanisms underlying antibiotic resistance phenotypes was also studied. Based on MLST typing, C. coli strains were genetically more conserved, with a predominant clonal complex (CC828), than C. jejuni strains. In contrast, C. coli isolates were genetically more variable than C. jejuni with regard to flaA-SVR typing. A high rate of resistance was observed for quinolones (100% to nalidixic acid, >90% to ciprofloxacin) and, in general, resistance was more common among C. coli, especially for erythromycin (40.2% vs. 6.7%). In addition, most isolates (86%) were resistant to multiple antimicrobial families. Besides the expected point mutations associated with antibiotic resistance, detected polymorphisms in the cmeABC locus likely play a role in the multiresistant phenotype. This study provides for the first time an overview of the genetic diversity of Campylobacter strains from Portugal. It also shows a worrying antibiotic multiresistance rate and the emergence of Campylobacter strains resistant to antibiotics of human use. PMID- 25130099 TI - Value of integron detection for predicting antibiotic resistance in patients with Gram-negative septicaemia. AB - Multidrug-resistant Enterobacteriaceae are a major public health threat and complicate the choice of drugs for empirical antibiotic therapy, especially in sepsis patients who require rapid, appropriate treatment. The objective of this study was to examine the value of integrons as a global predictive marker of acquired antibiotic resistance in septicaemia-causing Enterobacteriaceae by direct detection in positive blood cultures. The integron genetic marker can be detected in a single test, whereas multiple PCRs are needed to detect the hundreds of known antibiotic resistance genes. A total of 166 positive blood cultures were included in the study, and integrons were detected with a quantitative PCR method both in positive blood cultures and isolated Enterobacteriaceae. The results of integron detection directly on positive blood cultures were consistent in 98.8% of cases with integron detection in isolated Enterobacteriaceae. Negative predictive values (NPVs) were >90% for resistance to third-generation cephalosporins, aminoglycosides, ciprofloxacin and trimethoprim/sulfamethoxazole. In the current context of antibiotic stewardship, these good NPVs indicate that this method might be useful for preserving broad spectrum antibiotics. The results of this proof-of-concept study must be confirmed in order to demonstrate the clinical relevance of integron detection, not only in positive blood cultures but also, to gain time, in raw biological samples. PMID- 25130100 TI - Background activities, induction, and behavioral allocation in operant performance. AB - In experiments on operant behavior, other activities, called "background" activities, compete with the operant activities. Herrnstein's (1970) formulation of the matching law included background reinforcers in the form of a parameter rO, but remained vague about the activities (BO) that produce rO. To gain more understanding, we analyzed data from three studies of performance with pairs of variable-interval schedules that changed frequently in the relative rate at which they produced food: Baum and Davison (2014), Belke and Heyman (1994), and Soto, McDowell, and Dallery (2005). Results sometimes deviated from the matching law, suggesting variation in rO. When rO was calculated from the matching equation, two results emerged: (a) rO is directly proportional to BO, as in a ratio schedule; and (b) rO and BO depend on the food rate, which is to say that BO consists of activities induced by food, as a phylogenetically important event. Other activities unrelated to food (BN ) correspond to Herrnstein's original conception of rO and may be included in the matching equation. A model based on Baum's (Baum, 2012) concepts of allocation, induction, and contingency explained the deviations from the matching law. In the model, operant activity B, BO, and BN competed unequally in the time allocation: B and BO both replaced BN , BO replaced lever pressing (Soto et al.), and key pecking replaced BO (Baum & Davison). Although the dependence of rO and BO on food rate changes Herrnstein's (1970) formulation, the model preserved the generalized matching law for operant activities by incorporating power-function induction. PMID- 25130098 TI - Surveillance study of Treponema pallidum harbouring tetracycline resistance mutations in patients with syphilis. PMID- 25130102 TI - Superficial siderosis and spinal intradural extramedullary cavernous angioma. PMID- 25130101 TI - The anthropometry of children and adolescents may be influenced by the prenatal smoking habits of their grandmothers: a longitudinal cohort study. AB - OBJECTIVES: Previously, in the Avon Longitudinal Study of Parents and Children (ALSPAC), we have shown different sex-specific birth anthropometric measurements contingent upon whether or not prenatal smoking was undertaken by paternal grandmother (PGM+/-), maternal grandmother (MGM+/-), and the study mother (M+/-). The findings raised the question as to whether there were long-term associations on the growth of the study children over time. METHODS: Measures of weight, height, body mass index, waist circumference, lean mass, and fat mass of children in the ALSPAC study from 7 to 17 years of age were used. We compared growth in four categories at each age: PGM+M- with PGM-M-; MGM+M- with MGM-M-; PGM+M+ with PGM-M+; MGM+M+ with MGM-M+; and adjusted for housing tenure, maternal education, parity, and paternal smoking at the start of the study pregnancy. RESULTS: We found that if the PGM had, but the study mother had not, smoked in pregnancy, the girls were taller and both genders had greater bone and lean mass. However, if the MGM had smoked prenatally but the mother had not (MGM+M-), the boys became heavier than expected with increasing age-an association that was particularly due to lean rather than fat mass, reflected in increased strength and fitness. When both the maternal grandmother and the mother had smoked (MGM+M+) girls had reduced height, weight, and fat/lean/bone mass when compared with girls born to smoking mothers whose own mothers had not smoked (MGM-M+). CONCLUSIONS: This study indicates that smoking in humans can have sex-specific transgenerational effects. PMID- 25130103 TI - Spasm provocation tests performed under medical therapy: a new approach for treating patients with refractory coronary spastic angina on emergency admission. AB - Objective There are no objective methods for evaluating the severity of vasospasms in patients with refractory coronary spastic angina (R-CSA) under adequate medical therapy. We examined whether spasm provocation tests performed under adequate medication are useful for evaluating the severity of disease in R CSA patients on emergency admission. Methods and Results We performed spasm provocation tests before and after the administration of medical therapy in eight R-CSA patients, including one ventricular fibrillation survivor (VF-S) and seven patients with unstable angina (UAP) on emergency readmission. We also performed these tests only after medical therapy on urgent admission in four R-CSA patients, including two patients with UAP, one patient with VF-S and one patient with acute coronary syndrome. All 12 R-CSA patients had been medicated with >= 2 vasodilator drugs. Positive coronary spasms were defined as >99% transient narrowing. The coronary artery spasms disappeared in three patients under medication, and mitigation of vasospasticity was observed in three patients. In these six cases we continued the same medications. Meanwhile in two patients, we recommended a consultation for psychosomatic medicine. In contrast, the remaining six R-CSA patients exhibited higher levels of vasospasticity, irrespective of the administration of aggressive medical therapy, in which the doses of vasoactive drugs were increased in order to suppress coronary artery spasms. Conclusion In some R-CSA patients on emergency admission, performing spasm provocation tests under medical therapy is useful for determining the subsequent treatment strategy. Therefore, this test may become a new tool in the treatment of R-CSA. PMID- 25130104 TI - A pilot study to examine the management of asymptomatic hyperparathyroidism in Japanese patients in accordance with the guidelines for asymptomatic PHPT proposed at the Third International Workshop in 2008. AB - Objective The treatment for asymptomatic primary hyperparathyroidism (PHPT) remains controversial. In 2008, the Third International Workshop on the Management of Asymptomatic PHPT proposed a set of guidelines for the management of asymptomatic PHPT. We therefore evaluated the application of the Workshop recommendations in Japanese patients with asymptomatic PHPT. Methods We analyzed each parameter of the guidelines in 87 Japanese patients with asymptomatic PHPT who underwent methoxy-isobutyl-isonitrile (MIBI) scintigraphy. Results Fewer than 10% of the patients were less than 50 years of age. The bone mineral density T score was below -2.5 SD in 20 women (46.5% of all women analyzed) and in none of the men. The eGFR was <60 mL/min/1.73 m(2) in 17 patients. A majority of patients (43) satisfied only one parameter, while 25 patients satisfied none of the parameters. Furthermore, the MIBI-positive and surgically treated patients tended to satisfy a larger number of the parameters. The Workshop criteria and levels of PTH, daily Ca excretion, serum ALP and 1,25(OH)2 Vitamin D were further analyzed in relation to the findings of MIBI scans, and almost all of the parameters were found to be significantly correlated with the results of the MIBI studies. Conclusion Our results suggest the need to reassess the Workshop guidelines for the treatment of hyperparathyroidism in Japanese patients. It is desirable that MIBI scintigraphy be performed whenever possible, as this modality is anticipated to play an important role in determining whether or not surgery is appropriate. PMID- 25130105 TI - Oral tacrolimus for megacolon in patients with severe ulcerative colitis. AB - Toxic megacolon is an infrequent but life-threatening complication that occurs most commonly in patients with severe ulcerative colitis. Intravenous steroids are often recommended for patients with toxic megacolon secondary to ulcerative colitis. However, steroid dependency may mask the presence of intra-abdominal sepsis and is associated with refractoriness, during which cytomegalovirus reactivation may occur. In this report, we present two rare cases of megacolon accompanying pancolonic severe ulcerative colitis that were successfully treated with oral tacrolimus, including one steroid-naive patient. In cases of ulcerative colitis with megacolon, treatment with oral tacrolimus is recommended, thereby avoiding steroid dependency and improving the long-term prognosis. PMID- 25130106 TI - Successful treatment with entecavir for reactivation of hepatitis B virus following systemic chemotherapy in a hepatitis B surface antigen-negative patient with colorectal cancer. AB - Reactivation of hepatitis B virus (HBV) has recently been reported as a fatal complication in patients undergoing cytotoxic chemotherapy. We herein describe a case of reactivation in a 76-year-old man who had undergone pelvic exenteration for colorectal cancer (CRC). He was treated with a modified FOLFOX6 chemotherapy regimen after the operation. Thirteen months later, his laboratory data showed severe liver dysfunction. His hepatitis B surface antigen (HBsAg) test was positive, and his HBV-DNA level was elevated. We diagnosed the patient with HBV reactivation as his HBsAg test was negative before starting chemotherapy. His liver dysfunction improved after administration of entecavir. This is the first report describing HBV reactivation following chemotherapy for an HBsAg-negative CRC patient. PMID- 25130107 TI - Alcoholic liver disease complicated by deep bleeding into the muscles or retroperitoneum: report of three cases and a review of the literature. AB - We herein report three cases of alcoholic cirrhosis complicated by deep bleeding. In two of the three cases, intramuscular or retroperitoneal hematomas developed spontaneously. In contrast, in the remaining case, an intramuscular hematoma developed after trauma. In the former two patients, the intramuscular hematomas recurred at other sites during hospitalization. All three patients received conservative therapy, and one patient with a retroperitoneal hematoma underwent transcatheter arterial embolization. All of the patients eventually died of liver failure. The occurrence of severe alcoholic liver disease with deep bleeding has recently been reported with increasing frequency, and clinicians should bear this condition in mind as a life-threatening complication of alcoholic liver disease. PMID- 25130109 TI - Life-threatening acute heart failure due to primary cardiac undifferentiated pleomorphic sarcoma. AB - A 41-year-old man was admitted with acute heart failure and shock status. An echocardiogram showed a mobile tumor obstructing blood flow through the mitral valve with a stalk on the posterior left atrium (LA) wall. Emergent open-heart surgery was performed to resect the tumor (77*36*30 mm). Histological examination confirmed that it was an undifferentiated pleomorphic sarcoma. Unfortunately, positron emission tomography performed five months after surgery demonstrated a local recurrence around the right pulmonary vein and LA. We performed proton beam radiotherapy to treat the local recurrence, and it was effective. The patient has survived more than one year since the first life-threatening heart failure episode. PMID- 25130108 TI - Double-valve replacement for mitral and aortic regurgitation in a Patient with Libman-Sacks endocarditis. AB - A 53-year-old woman with systemic lupus erythematosus and antiphospholipid syndrome presented with central nervous system (CNS) lupus and vegetation of the mitral and aortic valves. Her CNS lupus was relieved with methylprednisolone pulse therapy; however, her mitral regurgitation worsened, and she developed acute decompensated heart failure. The mitral and aortic valves were replaced with mechanical heart valves. Microscopic examination of the excised valves showed no bacterial invasion, and Libman-Sacks (LS) endocarditis of both valves was confirmed. This was a case of LS endocarditis with clear vegetation that spread over the mitral and aortic valves. PMID- 25130110 TI - A rare presentation of subclinical Cushing's syndrome as a pubic fracture. AB - Osteoporosis and bone fractures are commonly seen in patients with Cushing's syndrome (CS). Fractures usually occur in the vertebrae and ribs whereas pubic fractures are less common. Similar to obvious hypercortisolemia, subclinical hypercortisolemia can increase the risk of fractures. However, in subclinical cases, bone fractures are very rarely seen as the presenting symptom. We herein report the case of a 62-year-old postmenopausal woman who was presented with a pubic fracture. During the evaluation of the fracture, thoracoabdominal magnetic resonance imaging of the patient demonstrated an adrenal mass. Although the patient did not show any signs of overt hypercortisolism, an endocrinologic evaluation revealed hypercortisolism due to an adrenal tumor. Adrenalectomy was performed, which resulted in a cure of the disease. During the orthopedic follow up, the patient's pubic area pain gradually improved, and the pubic fracture healed without any accompanying new bone fractures. One year after the surgery, a remarkable improvement was detected in the patient's bone density in spite of the lack of administration of any medications for osteoporosis. Subclinical CS can present as a pubic fracture, and awareness of this relationship can help physicians to diagnose the disease. PMID- 25130111 TI - Coexistence of gastrointestinal stromal tumors (GISTs) and pheochromocytoma in three cases of neurofibromatosis type 1 (NF1) with a review of the literature. AB - It is well known that neurofibromatosis type 1 (NF1) is uncommonly associated with pheochromocytoma development and also, to a larger extent, with gastrointestinal stromal tumors (GISTs). We herein document three cases with the rare condition of NF1 coexisting with GIST and pheochromocytoma, while one of them also has a composite tumor and another has papillary thyroid carcinoma. PMID- 25130113 TI - A rare case of acquired methemoglobinemia associated with alkaptonuria. AB - We herein present a rare case of acquired methemoglobinemia associated with alkaptonuria. Alkaptonuria is a congenital error of metabolism caused by the deficiency of homogentisic acid oxidase, which subsequently results in the accumulation of homogentisic acid (HGA) in body tissues. As renal dysfunction progresses, the level of HGA excretion in the urine decreases and the blood concentration of HGA increases. HGA oxidizes oxyhemoglobin to methemoglobin, which can induce multiple organ failure accompanied by tissue hypoxia, intravascular hemolysis and metabolic acidosis. The mortality of this disease is high when alkaptonuria is associated with the presence of methemoglobinemia; therefore, treatment should be carefully planned in such cases. PMID- 25130112 TI - Liraglutide as a potentially useful agent for regulating appetite in diabetic patients with hypothalamic hyperphagia and obesity. AB - Hypothalamic hyperphagia and obesity are characterized by a lack of satiety and an abnormally high appetite that is difficult to control. We herein report the cases of two patients with hypothalamic hyperphagia and obesity with MRI detectable hypothalamic lesions. These patients suffered from diabetes mellitus associated with an abnormal eating behavior and weight gain. Liraglutide was successfully used to treat their diabetes mellitus and suppress their abnormal appetites. Glucagon-like peptide-1 analogues, including liraglutide, are promising treatment options in patients with hypothalamic hyperphagia and obesity, as these agents enhance the hypothalamic input of the satiety signal, which is lacking in such patients. PMID- 25130114 TI - Marked elevation of serum hyaluronan levels in collagenofibrotic glomerulopathy. AB - Collagenofibrotic glomerulopathy is a rare glomerular disease characterized by the massive deposition of type III collagen in mesangial and subendothelial spaces. We observed markedly increased serum hyaluronan levels in patients with collagenofibrotic glomerulopathy; levels in three patients were more than 1,000 times greater than the normal upper limit. However, one kidney transplant patient had normal serum hyaluronan levels. We found that serum levels and activities of the enzyme hyaluronidase were normal, and hyaluronan was not markedly deposited in the mesangial or subendothelial spaces. Our findings suggest that serum hyaluronan levels may be a specific diagnostic marker of collagenofibrotic glomerulopathy, and kidney transplantation may alleviate marked increases in serum hyaluronan. PMID- 25130115 TI - Severe hypokalemia and thyrotoxic paralysis from painless thyroiditis complicated by life-threatening polymorphic ventricular tachycardia and rhabdomyolysis. AB - A 61-year-old man presented with lower extremity paralysis and severe hypokalemia. His thyroid function test showed thyrotoxicosis. Despite attempts to correct his hypokalemia, he developed pulseless polymorphic ventricular tachycardia two hours later. He was successfully resuscitated after defibrillation. We performed continuous venovenous hemodiafiltration for 10 days due to acute kidney injury and rhabdomyolysis. We observed life-threatening polymorphic ventricular tachycardia requiring urgent defibrillation, as well as rhabdomyolysis requiring dialysis during the transient thyrotoxic phase of painless thyroiditis. Pay attention to the possibility of the development of life threatening ventricular tachycardia associated with hypokalemia in the setting of thyroiditis and thyrotoxic paralysis. PMID- 25130116 TI - Diffuse parenchymal pulmonary amyloidosis showing an objective response to bortezomib-based chemotherapy. AB - A 77-year-old woman was admitted because of bilateral hand numbness and dyspnea on exertion. Her serum IgG was increased, and a bone marrow aspiration analysis supported a diagnosis of multiple myeloma. Additionally, computed tomography scans of the chest showed bilateral ground glass attenuations, linear opacities, and consolidations. Transbronchial lung biopsy revealed Congo Red-positive amorphous eosinophilic deposits. She was therefore diagnosed with diffuse parenchymal pulmonary amyloidosis accompanied by multiple myeloma. Following combination chemotherapy including bortezomib, her serum monoclonal protein levels were normalized, and pulmonary function and oxygenation improved. PMID- 25130117 TI - Bevacizumab for critical brain metastases in a patient with pulmonary pleomorphic carcinoma. AB - Bevacizumab was initially contraindicated in patients with brain metastases, but several reports have shown the efficacy and safety of bevacizumab for brain metastases. We herein report the case of a patient with pulmonary pleomorphic carcinoma for which bevacizumab plus weekly paclitaxel following whole-brain radiotherapy (WBRT) was effectively and safely administered for critical and refractory brain metastases. Although the 50-year-old male patient received WBRT with anti-edema therapies for progressive brain metastases, his clinical symptoms deteriorated rapidly. After the completion of WBRT, we administered bevacizumab plus weekly paclitaxel, and his neurological symptoms improved dramatically. Brain magnetic resonance imaging demonstrated a marked response by the brain metastases and improved brain edema. This case suggested both synergism between WBRT and bevacizumab, and an anti-edema effect of bevacizumab. Bevacizumab may be therefore a potent therapeutic option for patients with refractory brain metastases. PMID- 25130118 TI - Esophagomediastinal fistula secondary to multidrug-resistant tuberculous mediastinal lymphadenitis. AB - Esophagomediastinal fistula secondary to mediastinal tuberculosis (TB) lymphadenitis is a rare and unusual complication. A 32-year-old woman visited our clinic because of chest pain. Computed tomography (CT) demonstrated an esophagomediastinal fistula with subcarinal lymphadenopathy and no remarkable parenchymal lung lesions. The esophagomediastinal fistula was confirmed by esophagoscopy; however, the patient's bronchoscopy findings were unremarkable. The endobronchial ultrasound-guided lymph node aspiration did not confirm a diagnosis of TB. Finally, the patient was diagnosed via a lymph node biopsy. A drug-sensitivity test revealed the presence of a multidrug-resistant pathogen. To the best of our knowledge, this is the first case of esophagomediastinal fistula secondary to multidrug-resistant (MDR-) TB mediastinal lymphadenitis. PMID- 25130119 TI - Wandering pneumonia caused by dabigatran. AB - We herein describe the case of a 74-year-old man who experienced pulmonary consolidation and chest pain following administration of dabigatran, a novel oral anticoagulant. The consolidation settled spontaneously in another lung area, a condition sometimes referred to as "wandering pneumonia." Although we did not find specific pathological evidence of interstitial lung disease on transbronchial lung biopsy, a lung opacity spontaneously disappeared following discontinuance of dabigatran, and there was no recurrence. There are no other reports of dabigatran-induced lung injury, except alveolar hemorrhage and eosinophilic pneumonia. We should consider that any novel drug could cause various types of pulmonary injuries. PMID- 25130120 TI - Chronic thromboembolic pulmonary hypertension complicated by a cavitating lung infection caused by Mycobacterium intracellulare. AB - A 35-year-old man with a six-month history of progressive exertional dyspnea was referred to our institution. He had been diagnosed with Mycobacterium intracellulare pulmonary infection with lung cavitation two years earlier, and was being followed up without any medications. After being referred to our hospital, he underwent computed tomographic pulmonary angiography, which indicated a pulmonary thrombus and lung cavitation. Furthermore, right heart catheterization confirmed pulmonary hypertension, and we made a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Following successful pulmonary endarterectomy, the patient's symptoms and hemodynamics were significantly improved, with the disappearance of lung cavitation. It is important to suspect CTEPH in patients with unaccountable infectious lung cavities. PMID- 25130121 TI - Lung adenocarcinoma complicated by Trousseau's syndrome successfully treated by a combination of anticoagulant therapy and chemotherapy. AB - A 63-year-old woman was diagnosed with advanced lung adenocarcinoma complicated by Trousseau's syndrome characterized by non-bacterial thrombotic endocarditis, asymptomatic brain infarction, deep venous thrombosis, and low-grade disseminated intravascular coagulation (DIC). The patient's DIC rapidly became widespread, and multiple micropulmonary embolisms led to severe respiratory failure. She received a blood transfusion and anticoagulant treatment with heparin and recombinant human soluble thrombomodulin, which modestly ameliorated her symptoms, and additional chemotherapy led to tumor shrinkage with concomitant resolution of Trousseau's syndrome. Although there are no established medical approaches for managing Trousseau's syndrome, intensive anticoagulant treatment may be effective for improving the patients' general condition in order for them to be able to undergo subsequent combination chemotherapy. PMID- 25130122 TI - Acquired factor X deficiency associated with atypical AL-amyloidosis. AB - We herein describe the case of a 77-year-old woman with acquired factor X deficiency that was likely caused by atypical amyloidosis. The patient developed severe gastrointestinal bleeding as a result of a significant decrease of factor X activity. Neither proteinuria nor diarrhea was observed as an initial manifestation. Although a bone marrow examination revealed direct fast scarlet positive extracellular deposits, they did not exhibit red-to-green dichroism under polarized light. Immunofluorescence microscopy showed that the fibrillar proteins were positive for CD138 but negative for beta2-microglobulin or amyloid A antibodies. These atypical pathological features of immunoglobulin light chain amyloidosis in this patient might be related to its unique clinical presentation. PMID- 25130123 TI - Crystalglobulinemia with fulminant course with cylinder-like bodies on peripheral blood smear. AB - A 63-year-old woman presented to our hospital with fever, purpura and pain in both legs and died 4 days after admission. Her blood smear and skin biopsy showed cylinder-like bodies (20*120 MUm). She was diagnosed to have monoclonal gammopathy (IgG, lambda type). An autopsy revealed cylinder-like bodies in the vasculature of various organs. We noted a proliferation of atypical plasma cells in her bone marrow, suggesting pre-existing myeloma. Crystalglobulinemia is a rare manifestation of hypergammaglobulinemia that can cause multiple embolisms of the small vessels, and this resulted in the patient's fulminant course. The identification of cylinder-like bodies in the peripheral blood may help in reaching a diagnosis in such cases. PMID- 25130124 TI - Bortezomib-induced posterior reversible encephalopathy syndrome: clinical and imaging features. AB - Posterior reversible encephalopathy syndrome (PRES) is a rare and potentially harmful complication in patients receiving targeted chemotherapy. We herein present a case of PRES that occurred after 33 days of high-dose bortezomib treatment and propose both overwhelmed cerebral autoregulation and toxin-mediated blood-brain barrier damage as the underlying mechanisms based on the imaging findings. A favorable recovery was observed two days after achieving stringent hypertension control and withholding bortezomib. Follow-up images obtained two weeks later unveiled a dramatic remission, with faint areas of subcortical hyperintensity in the bilateral parieto-occipital regions. With explicit clinical and imaging features, this case highlights the need for early recognition of PRES during the clinical course of bortezomib therapy. PMID- 25130125 TI - An aberrant subclavian artery exhibiting the partial steal phenomenon in a patient with VACTERL association. AB - We herein report the case of a 22-year-old Caucasian man with known vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, cardiac defects, renal and limb anomalies (VACTERL) association who presented with a headache and vertigo following the sudden and temporary loss of consciousness while attending a concert four days before admission to the hospital. On a physical examination, the following findings were found: a low body height, low set ears, thoracic scoliosis and a mild holosystolic heart murmur. A neurosonological examination revealed a partial subclavian steal phenomenon. CT angiography of the neck vessels and aortic arch confirmed an anomalous right subclavian artery -known as the lusorian artery. Further studies are warranted in patients with VACTERL in order to identify possible links between the prevalence of an aberrant right subclavian artery (lusorian artery) and possible congenital subclavian steal syndrome or dysphagia lusoria. In addition, duplex ultrasound of the carotid and vertebral arteries may be performed as part of screening examinations in patients with congenital syndromes. PMID- 25130126 TI - Spinal intradural extramedullary cavernous angioma presenting with superficial siderosis and hydrocephalus: a case report and review of the literature. AB - A 36-year-old man with progressive hearing impairment visited our hospital complaining of a severe headache. A neurological examination revealed bilateral sensorineural hearing impairment, mild ataxia, hyperreflexia and mild cognitive dysfunction. Brain MRI demonstrated hydrocephalus and typical hypointensity rimming the brain surface on T2(*)-weighted images. The patient was diagnosed as having superficial siderosis. Spinal MRI disclosed the presence of a lumbar intradural extramedullary mass. The surgically resected tumor was histologically found to be a cavernous angioma. Superficial siderosis is an important cause of hearing loss. With respect to the detection of disorders underlying this pathological condition, MRI examinations, including those of the brain and whole spinal cord, are recommended. PMID- 25130127 TI - A rare case of diffuse pulmonary nodules in a patient with adult-onset Still's disease. AB - Adult-onset Still's disease (AOSD) is a multisystemic inflammatory disorder, but pulmonary involvement is rare. We herein describe the case of a woman diagnosed with AOSD; treatment resolved her symptoms, but nine days later she was admitted with pyrexia and a productive cough. A chest X-ray revealed diffuse pulmonary nodules and patchy shadows. A high-resolution chest computed tomography scan confirmed diffuse infiltration in the pulmonary parenchyma, signs of alveolar nodules, distribution along the lobule center, several areas of tree-in-bud patterns, and bilateral pleural effusion. The patient was treated with high doses of corticosteroids, which rapidly reduced the size of her diffuse pulmonary nodules and dramatically improved her pleural effusion. PMID- 25130128 TI - Grade 3 lymphomatoid granulomatosis in a patient receiving methotrexate therapy for rheumatoid arthritis. AB - Lymphomatoid granulomatosis (LyG) is a rare, B-cell derived, lymphoproliferative disorder that often presents as pulmonary nodular lesions with a histopathology of lymphatic invasion of the vascular wall. The development of LyG may be associated with reactivation of the Epstein-Barr virus under an immunosuppressive state. We herein report a case of Grade 3 LyG that developed during methotrexate therapy for rheumatoid arthritis and regressed following the withdrawal of the drug. PMID- 25130129 TI - Elizabethkingia meningoseptica as an unusual pathogen causing healthcare associated bacteriuria. AB - Elizabethkingia meningoseptica is recovered from urine samples in very unusual cases, although the clinical significance of its detection remains unclear. Four cases of E. meningoseptica bacteriuria were analyzed, and E. meningoseptica was found to be the causative agent of healthcare-associated bacteriuria, including urinary tract infections, asymptomatic bacteriuria and transient bacteriuria, primarily in elderly patients with diabetes. Although E. meningoseptica cultured from urine was found to be resistant to most antimicrobial agents, bacteriuria caused by E. meningoseptica resolved in all four cases. However, instances of death have also been previously reported. PMID- 25130130 TI - Prevotella brain abscesses and stroke following dental extraction in a young patient: a case report and review of the literature. AB - A brain abscess is a life-threatening infection. There are few reports describing Prevotella bacteremia with middle cerebral artery (MCA) occlusion and brain abscess following dental extraction in the literature. We herein describe a 32 year-old healthy man who experienced headache after tooth extraction. He was not correctly diagnosed until he experienced a stroke and a blood culture revealed Prevotella denticola weeks later. This case and our detailed review of related cases highlight the importance of thorough medical history-taking and clinical evaluations. Brain abscess formation should be considered in previously healthy patients with fever, stroke, and a recent history of tooth extraction. PMID- 25130131 TI - Spontaneous esophageal perforation with a posterior mediastinal hematoma. PMID- 25130132 TI - Localized infarction of the lateral geniculate body. PMID- 25130134 TI - Reducing radiation, revising reference levels. PMID- 25130133 TI - Exploring arrays of vertical one-dimensional nanostructures for cellular investigations. AB - The endeavor of exploiting arrays of vertical one-dimensional (1D) nanostructures (NSs) for cellular applications has recently been experiencing a pronounced surge of activity. The interest is rooted in the intrinsic properties of high-aspect ratio NSs. With a height comparable to a mammalian cell, and a diameter 100-1000 times smaller, NSs should intuitively reach far into a cell and, due to their small diameter, do so without compromising cell health. Single NSs would thus be expedient for measuring and modifying cell response. Further organization of these structures into arrays can provide up-scaled and detailed spatiotemporal information on cell activity, an achievement that would entail a massive leap forward in disease understanding and drug discovery. Numerous proofs-of-principle published recently have expanded the large toolbox that is currently being established in this rapidly advancing field of research. Encouragingly, despite the diversity of NS platforms and experimental conditions used thus far, general trends and conclusions from combining cells with NSs are beginning to crystallize. This review covers the broad spectrum of NS materials and dimensions used; the observed cellular responses with specific focus on adhesion, morphology, viability, proliferation, and migration; compares the different approaches used in the field to provide NSs with the often crucial cytosolic access; covers the progress toward biological applications; and finally, envisions the future of this technology. By maintaining the impressive rate and quality of recent progress, it is conceivable that the use of vertical 1D NSs may soon be established as a superior choice over other current techniques, with all the further benefits that may entail. PMID- 25130135 TI - Temporal effect of inertial cavitation with and without microbubbles on surface deformation of agarose S gel in the presence of 1-MHz focused ultrasound. AB - Sonoporation has the potential to deliver extraneous molecules into a target tissue non-invasively. There have been numerous investigations of cell membrane permeabilization induced by microbubbles, but very few studies have been carried out to investigate sonoporation by inertial cavitation, especially from a temporal perspective. In the present paper, we show the temporal variations in nano/micro-pit formations following the collapse of inertial cavitation bubbles, with and without Sonazoid(r) microbubbles. Using agarose S gel as a target material, erosion experiments were conducted in the presence of 1-MHz focused ultrasound applied for various exposure times, Tex (0.002-60 s). Conventional microscopy was used to measure temporal variations in micrometer-scale pit numbers, and atomic force microscopy utilized to detect surface roughness on a nanometer scale. The results demonstrated that nanometer-scale erosion was predominantly caused by Sonazoid(r) microbubbles and C4F10 gas bubbles for 0.002 s C variant on leucovorin rescue and risk of relapse in childhood acute lymphoblastic leukemia treated with high-dose methotrexate. AB - BACKGROUND: Recent studies suggest that SLCO1B1 c.521T > C variant decreases the clearance of methotrexate (MTX) and elevates its plasma concentration, hence leucovorin doses may need to be adjusted. However, high leucovorin doses may affect the cure rate in childhood acute lymphoblastic leukemia (ALL). Hitherto neither the appropriate dose of leucovorin in carriers of SLCO1B1 c.521T > C variant nor the impact of SLCO1B1 polymorphism on the risk of ALL relapse has been clarified. PROCEDURE: A double-blind and controlled study was conducted in 136 children with ALL. They were genotyped for rs4149056 single nucleotide polymorphism into wild-type group and variant group, and received MTX at 3-5 g/m(2) . Plasma concentration MTX and its metabolite were determined by HPLC. The toxicity of MTX, dose of leucovorin and 5-year relapse rate of ALL were recorded. RESULTS: Compared with wild-type group, area under the concentration time curve of MTX increased by 4.2-fold and peripheral clearance rate decreased significantly in variant group. Patients carrying rs4149056 C allele endured a remarkable longer time above the MTX safety threshold and suffered from a higher frequency of toxicity, so 2.2-fold leucovorin was given. However, no association was found between SLCO1B1 c.521T > C variant and the relapse risk in five years. CONCLUSIONS: The SLCO1B1 c.521T > C variant was an important determinant of MTX disposition and their carriers were exposed to increased intensity and time of MTX. An appropriate leucovorin dose raise in variant group was beneficial to reducing the serious toxicity. The c.521T > C variant wasn't associated with the risk of ALL relapse. PMID- 25130191 TI - Investigation of the effects of some phenolic compounds on the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase from human erythrocytes. AB - Polyphenols are the important compounds that have various bioactivities. They constitute vital active agents of not only daily diet but also natural medicines that are used traditionally. It is generally considered that they are safe because they are natural. In some conducted studies, different negative effects of these compounds were mentioned. Twelve phenolic compounds have been assayed to determine the effect of inhibition on glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) enzymes activity. For in vitro studies, the enzymes were purified from human erythrocytes using 2',5'-ADP Sepharose 4B affinity chromatography. Naringenin, caffeic acid, ellagic acid, ferulic acid, and sinapic acid against two enzymes, hesperidin and polydatin, only on G6PD activity and chrysin solely against 6PGD showed inhibitory effect. Chlorogenic acid, p-coumaric acid, and syringic acid did not exhibit an effect on the activity of the two enzymes. PMID- 25130194 TI - A pilot study to develop an objective clinical score for canine otitis externa. AB - BACKGROUND: The lack of an accepted clinical scoring system in canine otitis externa makes it difficult to compare clinical trials. HYPOTHESIS/OBJECTIVES: To develop a score that is clinically relevant, reliable and sensitive to change. ANIMALS: Client-owned healthy dogs (n = 55) and dogs with otitis externa (n = 60). METHODS: We compared 0-3 and 0-5 assessments of erythema, oedema/swelling, erosion/ulceration, exudate and pain of the ear canals with a reference 0-2 scale. Additional data included odour, pruritus scores, tympanic membrane condition, treatment outcome and neutrophil, bacterial and Malassezia counts. RESULTS: There were no significant differences between the vertical and horizontal canal scores (correlation coefficients >0.93). Correlation coefficients for the 0-3 and 0-5 scales were also >0.9 for all parameters, but the 0-2 scale was more variable. Pain and pruritus did not correlate well with the lesion scores and were associated with suppurative and erythroceruminous otitis, respectively. Neutrophil and microbial counts were variable and could not be used to generate cut-off values to differentiate healthy and affected ears or determine the response to therapy. Total scores >=4 differentiated affected from healthy ears with 91.1% sensitivity and 100% specificity; scores <=3 were 100% sensitive and 91.9% specific for clinical success. The intra- and interobserver reliability was high (intraclass correlation coefficients >0.95 and Cohen's kappa coefficients >0.65). CONCLUSIONS AND CLINICAL IMPORTANCE: This pilot study showed that the 0-3 Otitis Index Score (OTIS3) for erythema, oedema/swelling, erosion/ulceration and exudate is suitable for further validation by a larger group of clinicians. PMID- 25130192 TI - Chronic activity-based therapy does not improve body composition, insulin-like growth factor-I, adiponectin, or myostatin in persons with spinal cord injury. AB - Spinal cord injury (SCI) induces dramatic changes in body composition including reductions in fat-free mass (FFM) and increases in fat mass (FM). OBJECTIVE: To examine changes in body composition in response to chronic activity-based therapy (ABT) in persons with SCI. DESIGN: Longitudinal exercise intervention. METHODS: Seventeen men and women with SCI (mean age=36.1+/-11.5 years) completed 6 months of supervised ABT consisting of load bearing, resistance training, locomotor training, and functional electrical stimulation. At baseline and after 3 and 6 months of ABT, body weight, body fat, and FFM were assessed using dual-energy X ray absorptiometry, and fasting blood samples were obtained to assess changes in insulin-like growth factor-I (IGF-I), adiponectin, and myostatin. RESULTS: Across all subjects, there was no change (P>0.05) in body weight, percent body fat, or FFM of the leg, arm, or trunk, whereas whole-body FFM declined (P=0.02, 50.4+/ 8.4 to 49.2+/-7.4 kg). No changes (P=0.21-0.41) were demonstrated in IGF-I, adiponectin, or myostatin during the study. CONCLUSIONS: Chronic ABT focusing on the lower extremity does not slow muscle atrophy or alter body fat, body mass, or regional depots of FFM in persons with SCI. Further, it does not induce beneficial changes in adiponectin, myostatin, or IGF-I. Alternative exercise based therapies are needed in SCI to reverse muscle atrophy and minimize the onset of related health risks. PMID- 25130193 TI - Polymorphisms in melanoma differentiation-associated gene 5 link protein function to clearance of hepatitis C virus. AB - Among patients newly infected with hepatitis C virus (HCV), only 20-30% clear the infection spontaneously. In the remaining 70% the infection persists, causing chronic liver inflammation and disease. It is well established that polymorphisms in host genes, especially in components of the innate immune response, contribute to the phenomenon of spontaneous HCV clearance. Retinoic acid inducible gene-I (RIG-I)-like helicases such as melanoma differentiation-associated gene 5 (MDA-5) are cytoplasmic sensors of viral RNA that are critical for triggering innate immune responses after infection with RNA viruses. We analyzed 14 nonsynonymous single-nucleotide polymorphisms in RIG-I-like helicase-pathway-genes comparing European patients who spontaneously cleared HCV (n = 285) or had persistent infection (n = 509). We found that polymorphic haplotypes in the MDA-5 gene IFIH1 encoding histidine at position 843 and threonine at position 946 strongly correlate with the resolution of HCV infection (odds ratio [OR]: 16.23; 95% confidence interval [CI]: 3.67-71.87; P = 1.1 * 10(-6) ). Overexpression of MDA-5 genetic variants in HEK 293 cells and in a tissue culture model of HCV infection revealed that the histidine 843/threonine 946 variant leads to increased baseline and ligand-induced expression of interferon-induced genes and confers an increased ability to suppress HCV replication. CONCLUSION: These data suggest that MDA-5 plays a significant role in the defense against HCV and that polymorphisms in MDA-5 can influence the outcome of HCV infection. PMID- 25130195 TI - Detection of Toxoplasma gondii DNA in fresh and frozen semen from rams in Brazil. AB - The aim of this study was to estimate the prevalence of genomic DNA of Toxoplasma gondii in semen samples from commercial rams in artificial insemination centres in Brazil, as well as in fresh semen from rams in the northeast of Brazil. In total, 108 semen samples were obtained from artificial insemination centres, and genomic DNA of T. gondii was detected in 24 of 108 (22.2%). The prevalence of antibodies anti-Toxoplasma gondii among sheep on rural properties was 9.2% (10/109), and 100% of the semen samples of these animals were positive in the PCR for T. gondii DNA. The molecular identity was confirmed through sequencing, which indicated 99.9% similarity with the T. gondii DNA sequences stored in the GenBank. This study reports the first occurrence of T. gondii DNA in the semen of rams, which came from artificial insemination centres in Brazil, as well as the occurrence of T. gondii DNA in the fresh semen of naturally infected rams in the northeast of Brazil. PMID- 25130196 TI - Islet xenotransplantation: what is the optimal age of the islet-source pig? AB - BACKGROUND: The need for pig islet xenotransplantation in patients with type 1 diabetes is compelling; however, the ideal age at which islets should be isolated from the donor pig remains uncertain. Pig islet transplantation in primates, as a valuable pre-clinical model, has been explored using adult, neonatal, fetal pig islets, and also pancreatic primordia from pig embryos as beta cell donors. Neonatal pig islets have some advantages over adult and fetal islets, but the optimal age within the first month of life at which neonatal islets should be isolated and transplanted is as yet unclear. METHODS: In an attempt to answer this question, we carried out a literature search, but limited the search primarily to evidence in the clinically-relevant pig-to-non-human primate model. RESULTS: We identified surprisingly few studies in this model directed to this topic. Even in pig-to-rodent models, there were few definitive data. CONCLUSION: From the few data available to us, we conclude that pancreatectomy and islet isolation from neonatal pigs may have advantages over adult pigs and that isolation during the first week of life may have minor advantages over later weeks. PMID- 25130197 TI - Effects of exposure to mixed volatile organic compounds on the neurobehavioral test performance in a cross-sectional study of US adults. AB - While the environmental exposure to multiple volatile organic compounds (VOCs) is ubiquitous, its neurobehavioral effects are not well understood. We assessed the associations between short-term exposure to VOC mixtures and neurobehavioral test performances on 497 participants in the Third National Health and Nutrition Examination Survey, using quantile and ordinary least squares regression models. We grouped 10 blood VOCs into 3 mixtures based on the principal component analysis, where Mix1 included benzene, toluene, ethylbenzene, m-/p-xylene, o xylene, and styrene; Mix2 included chloroform and tetrachloroethene; and Mix3 included 1,1,1-trichloroethane and 1,4-dichlorobenzene. We found a general lack of significant adverse effects with exceptions limited to those with the worst performance (i.e. the top 10 percent) in the simple reaction time test, suggesting that these people were potentially more susceptible to impacts of VOC mixtures. However, further research is needed to clarify the neurobehavioral effects of chronic low-level exposure to VOC mixtures among the general population. PMID- 25130198 TI - The association of chemotherapy versus hormonal therapy and health outcomes among patients with hormone receptor-positive, HER2-negative metastatic breast cancer: experience from the patient perspective. AB - This study aimed to characterize the impact of metastatic breast cancer (MBC) and cancer treatments on health-related quality of life, treatment satisfaction, and daily productivity from the patient perspective. This was a cross-sectional survey of patients with MBC (USA, n = 200; EU, n = 160). Post-menopausal women aged >=50 years with hormone receptor positive (HR+), HER2-negative (HER2-) MBC, currently using hormonal therapy (HT) or using chemotherapy (CT) for <=1 year were recruited. Fifty three percent (n = 191) reported CT and 47% (n = 169) reported HT use. Adjusting for covariates, HT users reported greater health related quality of life (p < 0.05), greater satisfaction with treatment and better feelings about side-effects (p < 0.001). HT users reported less bother with treatment side-effects (0-5 scale, p < 0.001) and less activity impairment than CT users (p < 0.001). HT was associated with better patient-reported outcomes than CT in first-line MBC management. These findings should be taken into consideration while making treatment decisions for HR+/HER2- MBC. PMID- 25130199 TI - Yeast synthetic biology for the production of recombinant therapeutic proteins. AB - The production of recombinant therapeutic proteins is one of the fast-growing areas of molecular medicine and currently plays an important role in treatment of several diseases. Yeasts are unicellular eukaryotic microbial host cells that offer unique advantages in producing biopharmaceutical proteins. Yeasts are capable of robust growth on simple media, readily accommodate genetic modifications, and incorporate typical eukaryotic post-translational modifications. Saccharomyces cerevisiae is a traditional baker's yeast that has been used as a major host for the production of biopharmaceuticals; however, several nonconventional yeast species including Hansenula polymorpha, Pichia pastoris, and Yarrowia lipolytica have gained increasing attention as alternative hosts for the industrial production of recombinant proteins. In this review, we address the established and emerging genetic tools and host strains suitable for recombinant protein production in various yeast expression systems, particularly focusing on current efforts toward synthetic biology approaches in developing yeast cell factories for the production of therapeutic recombinant proteins. PMID- 25130201 TI - Quantitative developmental data in a phylogenetic framework. AB - Following the embryonic period of organogenesis, most development is allometric growth, which is thought to produce most of the evolutionary morphological divergence between related species. Bivariate or multivariate coefficients of allometry are used to describe quantitative developmental data and are comparable across taxa; as such, these coefficients are amenable to direct treatment in a phylogenetic framework. Mapping of actual allometric coefficients onto phylogenetic trees is supported on the basis of the evolving nature of growth programs and the type of character (continuous) that they represent. This procedure depicts evolutionary allometry accurately and allows for the generation of reliable reconstructions of ancestral allometry, as shown here with a previously published case study on rodent cranial ontogeny. Results reconstructed the signature allometric patterns of rodents to the root of the phylogeny, which could be traced back into a (minimum) Paleocene age. Both character and statistical dependence need to be addressed, so this approach can be integrated with phylogenetic comparative methods that deal with those issues. It is shown that, in this particular sample of rodents, common ancestry explains little allometric variation given the level of divergence present within, and convergence between, major rodent lineages. Furthermore, all that variation is independent of body mass. Thus, from an evolutionary perspective, allometry appears to have a strong functional and likely adaptive basis. PMID- 25130200 TI - Natural selection acts in opposite ways on correlated hormonal mediators of prenatal maternal effects in a wild bird population. AB - Maternal hormones are important mediators of prenatal maternal effects. Although many experimental studies have demonstrated their potency in shaping offspring phenotypes, we know remarkably little about their adaptive value. Using long-term data on a wild collared flycatcher (Ficedula albicollis) population, we show that natural selection acts in opposite ways on two maternally derived androgens, yolk androstenedione (A4) and yolk testosterone (T). High yolk A4 concentrations are associated with higher fitness, whereas high yolk T concentrations are associated with lower fitness. Natural selection thus favours females that produce eggs with high A4 and low T concentrations. Importantly, however, there exists a positive (non-genetic) correlation between A4 and T, which suggests that females are limited in their ability to reach this adaptive optimum. Thereby, these results provide strong evidence for an adaptive value of differential maternal androgen deposition, and a mechanistic explanation for the maintenance of variation in maternal investment in the wild. PMID- 25130202 TI - Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines. AB - Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARgamma2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis. PMID- 25130203 TI - Clinical risk factors for central lymph node metastasis in papillary thyroid carcinoma: a systematic review and meta-analysis. AB - BACKGROUND: Prophylactic central lymph node dissection (CLND) in clinically node negative patients remains controversial, and predictive factors for central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) are not well defined. Herein, we conducted a systematic review to quantify the clinicopathologic factors predictive for CLNM in patients with PTC. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane CENTRAL, Scopus and Wanfang Database) for studies published until July 2014 was performed. Cohort, case-control studies and randomized controlled trials that examined clinical risk factors of CLNM were included. RESULTS: Twenty-five studies (4 prospective and 21 retrospective studies) involving 7,719 patients met final inclusion criteria. From the pooled analyses, male gender (OR 1.93, 95% CI 1.40 to 2.64), tumour multifocality (OR 1.93, 95% CI 1.62 to 2.30), tumour size >0.5 cm (OR 3.48, 95% CI 2.24 to 5.41), capsular invasion (OR 1.91, 95% CI 1.36 to 2.67), extrathyroidal extension (OR 2.42, 95% CI 1.58 to 3.71), lymphovascular invasion (OR 13.29, 95% CI 5.61 to 31.48) and lateral lymph node metastasis (OR 14.33, 95% CI 5.34 to 38.50) were significantly associated with increased risk of CLNM, while age >45 years (OR 0.65, 95% CI 0.51 to 0.83) and lymphocytic thyroiditis (OR 0.70, 95% CI 0.53 to 0.92) resulted in decreased risk of CLNM. Bilaterality and tumour location were not significantly associated with CLNM development (all P > 0.05). CONCLUSIONS: Our analysis identified several clinicopathologic factors associated with CLNM. These findings may guide the necessity and extent of prophylactic CLND and ultimately improve the outcomes of patients with PTC. PMID- 25130204 TI - Direct observation of coherent oscillations in solution due to microheterogeneous environment. AB - We report, for the first time, direct observation of coherent oscillations in the ground-state of IR775 dye due to microheterogeneous environment. Using ultrafast near-infrared degenerate pump-probe technique centered at 800 nm, we present the dynamics of IR775 in a binary mixture of methanol and chloroform at ultra-short time resolution of 30 fs. The dynamics of the dye in binary mixtures, in a time scale of a few fs to ~740 ps, strongly varies as a function of solvent composition (volume fraction). Multi-oscillation behavior of the coherent vibration was observed, which increased with decreasing percentage of methanol in the dye mixture. Maximum number of damped oscillations were observed in 20% methanol. The observed vibrational wavepacket motion in the ground-state is periodic in nature. We needed two cosine functions to fit the coherent oscillation data as two different solvents were used. Dynamics of the dye molecule in binary mixtures can be explained by wavepacket motion in the ground potential energy surface. More is the confinement of the dye molecule in binary mixtures, more is the number of damped oscillations. The vibrational cooling time, tau2, increases with increase in the confinement of the system. The observed wavepacket oscillations in ground-state dynamics continued until 1.6 ps. PMID- 25130205 TI - Prospective comparison treatment of 595-nm pulsed-dye lasers for virgin port-wine stain. AB - BACKGROUND: Vbeam((r)) and Cynergy((r)) are 595-nm pulsed-dye laser (PDL) equipment options, both extensively used in the clinical treatment of port-wine stains (PWS). However, there has been no study conducted of the differences in PWS therapeutic outcomes across both devices. OBJECTIVES: To compare the efficacy and safety of Vbeam and Cynergy equipment in the treatment of PWS. METHODS: Twenty-two patients with PWS were included in this study and were treated with both Vbeam and Cynergy. Patients underwent three treatment sessions. Treatment parameters used were as follows: (i) Cynergy((r)) , Cynosure Corp., 595-nm wavelength, radiant exposure of 11 J cm(-2) , 2-ms pulse duration, 7-mm spot size, cold-air cooling system of level 3. (ii) Vbeam((r)) , Candela Corp., 595-nm wavelength, radiant exposure of 11 J cm(-2) , 1.5-ms pulse duration, 7-mm spot size, cryogen spray cooling (30 ms of cooling with a 20-ms delay). Clinical efficacy outcomes were evaluated by chromameter and visual assessment 2 months post-treatment. RESULTS: All patients were treated by both Vbeam and Cynergy on adjacent sites. Chromameter evaluation showed that the average blanching rate was 21.24% for Cynergy sites and 36.42% for Vbeam sites. This difference was statistically significant (P = 0.05), which suggests that PWS respond better to Vbeam than to Cynergy at the settings used in this study. No patients developed scarring or permanent pigmentation change. CONCLUSIONS: Compared with Cynergy, Vbeam may be more effective in the treatment of PWS. Despite using supposedly equivalent fluences in 595-nm PDLs, equivalent clinical results cannot be guaranteed. PMID- 25130207 TI - Developing Clinical Research Relationship: Views from Within. AB - The nature of the relationship between clinical investigator and research participant continues to be contested. The related discussions have largely focused on the doctor-researcher dichotomy thought to permeate the work of a clinical investigator with research participants, whom in turn occupy two corresponding roles: patient and subject. This paper contributes to current debates on the topic by providing a voice to research participants, whose perspectives have been largely invisible. It draws on 42 in-depth interviews conducted in Ghana and South Africa with respondents at different stages of involvement in clinical research, ranging from no experience in clinical research to enrollment in several clinical trials. The perspectives of all respondents were largely congruent and rooted in the common view that clinical research contributed to the improvement of local health. They went beyond the researcher/participant versus doctor/patient dichotomy, long established in research ethics, and preferred to view participants and investigators as partners working together to find ways to address local health needs. The conceptualization of investigator-participant relations as a partnership reinforced expectations of care, transparency and accountability, which were viewed as necessary expressions of mutuality and respect within equal collaborations. It is important to engage with these views in order to avoid antagonizing societal expectations and to build up long-term public trust, crucial for the continuous operation of clinical research. PMID- 25130206 TI - Parent-of-origin growth effects and the evolution of hybrid inviability in dwarf hamsters. AB - Mammalian hybrids often show abnormal growth, indicating that developmental inviability may play an important role in mammalian speciation. Yet, it is unclear if this recurrent phenotype reflects a common genetic basis. Here, we describe extreme parent-of-origin-dependent growth in hybrids from crosses between two species of dwarf hamsters, Phodopus campbelli and Phodopus sungorus. One cross type resulted in massive placental and embryonic overgrowth, severe developmental defects, and maternal death. Embryos from the reciprocal cross were viable and normal sized, but adult hybrid males were relatively small. These effects are strikingly similar to patterns from several other mammalian hybrids. Using comparative sequence data from dwarf hamsters and several other hybridizing mammals, we argue that extreme hybrid growth can contribute to reproductive isolation during the early stages of species divergence. Next, we tested if abnormal growth in hybrid hamsters was associated with disrupted genomic imprinting. We found no association between imprinting status at several candidate genes and hybrid growth, though two interacting genes involved in embryonic growth did show reduced expression in overgrown hybrids. Collectively, our study indicates that growth-related hybrid inviability may play an important role in mammalian speciation but that the genetic underpinnings of these phenotypes remain unresolved. PMID- 25130209 TI - Participant comprehension of research for which they volunteer: a systematic review. AB - PURPOSE: Evidence indicates that research participants often do not fully understand the studies for which they have volunteered. The aim of this systematic review was to examine the relationship between the process of obtaining informed consent for research and participant comprehension and satisfaction with the research. DESIGN: Systematic review of published research on informed consent and participant comprehension of research for which they volunteer using the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) Statement as a guide. METHODS: PubMed, Cumulative Index for Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trails, and Cochrane Database of Systematic Reviews were used to search the literature for studies meeting the following inclusion criteria: (a) published between January 1, 2006, and December 31, 2013, (b) interventional or descriptive quantitative design, (c) published in a peer-reviewed journal, (d) written in English, and (e) assessed participant comprehension or satisfaction with the research process. Studies were assessed for quality using seven indicators: sampling method, use of controls or comparison groups, response rate, description of intervention, description of outcome, statistical method, and health literacy assessment. FINDINGS: Of 176 studies identified, 27 met inclusion criteria: 13 (48%) were randomized interventional designs and 14 (52%) were descriptive. Three categories of studies included projects assessing (a) enhanced consent process or form, (b) multimedia methods, and (c) education to improve participant understanding. Most (78%) used investigator-developed tools to assess participant comprehension, did not assess participant health literacy (74%), or did not assess the readability level of the consent form (89%). Researchers found participants lacked basic understanding of research elements: randomization, placebo, risks, and therapeutic misconception. CONCLUSIONS: Findings indicate (a) inconsistent assessment of participant reading or health literacy level, (b) measurement variation associated with use of nonstandardized tools, and (c) continued therapeutic misconception and lack of understanding among research participants of randomization, placebo, benefit, and risk. While the Agency for Healthcare and Quality and National Quality Forum have published informed consent and authorization toolkits, previously published validated tools are underutilized. CLINICAL RELEVANCE: Informed consent requires the assessment of health literacy, reading level, and comprehension of research participants using validated assessment tools and methods. PMID- 25130210 TI - Maternal unresponsiveness and child disruptive problems: the interplay of uninhibited temperament and dopamine transporter genes. AB - This study examined how and why dopamine transporter (DAT1) susceptibility alleles moderate the relation between maternal unresponsiveness and young children's behavior problems in a disadvantaged, predominantly minority sample of 201 two-year-old children and their mothers. Using a multimethod, multisource design, the findings indicated that a genetic composite of DAT1 susceptibility alleles (rs27072, rs40184) potentiated associations between maternal unresponsive caregiving and increases in children's behavior problems 2 years later. Moderator mediated-moderation analyses further revealed that the DAT1 diathesis was more proximally mediated by the potentiating effects of children's uninhibited temperament in the pathway between maternal unresponsiveness and disruptive behavior problems. Results are interpreted in the context of supporting and advancing the biosocial developmental model (Beauchaine & Gatzke-Kopp, 2012). PMID- 25130208 TI - Assessing the effectiveness of the 'Incredible Years((r)) parent training' to parents of young children with ADHD symptoms - a preliminary report. AB - This study examined the effectiveness of an evidence-based parent training program in a real-world Scandinavian setting. Parents of 36 young children with or at risk of Attention Deficit Hyperactive Disorder (ADHD) self-referred to participate in the Incredible Years((r)) Parent Training Program (IYPT) through a Danish early intervention clinic. Using a benchmarking approach, we compared self report data with data from a recent efficacy study. Eight out of nine outcome measures showed comparable or higher magnitude of effect from pretest to posttest. Effects were maintained or improved across six months. The methodology of this study exemplifies a rigorous but feasible approach to assessing effectiveness when evidence-based US protocols are transferred into the existing Scandinavian service delivery. Findings suggest that IYPT can be implemented successfully as an easy-access early intervention to families of children with or at risk of ADHD. PMID- 25130211 TI - Persistent inflammation and its relationship to leptin and insulin in phases of bipolar disorder from acute depression to full remission. AB - OBJECTIVE: A proinflammatory phase with various immunomodulatory mechanisms has been noted in bipolar mania and major depression. Weight gain and increased production of leptin may be associated with immunomodulation and insulin resistance in bipolar disorder. However, immunomodulation and its linkage with leptin and insulin in the depressive episode of bipolar disorder remain unclear. We investigated alterations in inflammatory markers and their relationship with leptin and insulin levels in patients with phases of bipolar disorder from acute depression to full remission. METHODS: Thirty-two physically healthy bipolar I depressed patients aged <45 years and age- and sex-matched healthy controls participated in this study. We measured their circulating levels of leptin, insulin, high-sensitivity C-reactive protein (hs-CRP), soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 1 (sTNF-R1), and interleukin-1 receptor antagonist (IL 1Ra) in three phases, i.e., acute depression, subsequent partial remission, and full remission. RESULTS: In acute depression, subsequent partial remission, and full remission, patients with bipolar disorder had significantly higher mean levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R compared with control subjects. The IL-1Ra and sTNF-R1 levels in various affective phases were significantly correlated to body mass index, leptin level, circulating lipids, and medication status. The sIL-2R levels in the three affective phases were all independent of other inflammatory markers and clinical and laboratory variables. Patients showed no alteration of sIL-6R levels through the depressive episode. CONCLUSIONS: Patients with bipolar disorder in depressive episodes may exhibit persistent inflammation with elevated levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R but not sIL-6R from the acute phases to full remission. Only sIL-2R production seems to be tightly linked with the pathophysiology of bipolar depression and is independent of insulin and leptin levels. PMID- 25130213 TI - IMAGING DIAGNOSIS--ACUTE MESENTERIC ISCHEMIA ASSOCIATED WITH HYPERTROPHIC CARDIOMYOPATHY IN A CAT. AB - A middle-aged cat was presented with vomiting, diarrhea, and pelvic limb paresis. Radiography showed cardiomegaly, interstitial pulmonary infiltration, distended intestinal loops, and portal venous gas. Hypertrophic cardiomyopathy (HCM) was confirmed. On CT, thrombi were identified at the abdominal aorta, superior mesenteric artery, bilateral renal arteries, and cauda vena cava at the level of the iliac vein bifurcation. Dilated and gas-filled loops of bowel with a "paper thin wall" were observed on CT images and were considered indicative of necrotic bowel. This case report describes the CT findings of acute mesenteric ischemia associated with HCM in a cat. PMID- 25130212 TI - A comprehensive analysis of the cellular and EBV-specific microRNAome in primary CNS PTLD identifies different patterns among EBV-associated tumors. AB - Primary central nervous system (pCNS) posttransplant lymphoproliferative disorder (PTLD) is a complication of solid organ transplantation characterized by poor outcome. In contrast to systemic PTLD, Epstein-Barr virus (EBV)-association of pCNS PTLD is almost universal, yet viral and cellular data are limited. To identify differences in the pattern of EBV-association of pCNS and systemic PTLD, we analyzed the expression of latent and lytic EBV transcripts and the viral and cellular microRNAome in nine pCNS (eight EBV-associated) and in 16 systemic PTLD samples (eight EBV-associated). Notably although 15/16 EBV-associated samples exhibited a viral type III latency pattern, lytic transcripts were also strongly expressed. Members of the ebv-miR-BHRF1 and ebv-miR-BART clusters were expressed in virtually all EBV-associated PTLD samples. There were 28 cellular microRNAs differentially expressed between systemic and pCNS PTLD. pCNS PTLD expressed lower hsa-miR-199a-5p/3p and hsa-miR-143/145 (implicated in nuclear factor kappa beta and c-myc signaling) as compared to systemic PTLD. Unsupervised nonhierarchical clustering of the viral and cellular microRNAome distinguished non-EBV-associated from EBV-associated samples and identified a separate group of EBV-associated pCNS PTLD that displayed reduced levels of B cell lymphoma associated oncomiRs such as hsa-miR-155, -21, -221 and the hsa-miR-17-92 cluster. EBV has a major impact on viral and cellular microRNA expression in EBV associated pCNS PTLD. PMID- 25130215 TI - Plasmon modes in graphene: status and prospect. AB - Plasmons in graphene have unusual properties and offer promising prospects for plasmonic applications covering a wide frequency range, ranging from terahertz up to the visible. Plasmon modes have been recently studied in both free-standing and supported graphene. Here, we review plasmons in graphene with particular emphasis on plasmonic excitations in epitaxial graphene and on the influence of the underlying substrate on the screening processes. Although the theoretical comprehension of plasmons in supported graphene is still incomplete, several experimental results provide clues regarding the nature of plasmonic excitations in graphene on metals and semiconductors. Plasmon in graphene can be tuned by chemical doping and gating potentials. We show through selected examples that the adsorbates can be used to tune the plasmon frequency, while the intercalation of chemical species allows the decoupling of the graphene sheet from the substrate to recover the plasmon dispersion of pristine graphene. Finally, we also report intriguing effects due to many-body interaction, such as the excitations generated by electron-electron coupling (magnetoplasmons) and the composite modes arising from the coupling of plasmons with phonons and with charge carriers. PMID- 25130216 TI - Addressing asthma disparities using clinical decision support in the electronic health record. PMID- 25130217 TI - From underrepresented minority high school student to medical school faculty member: how an outreach program changed my life. PMID- 25130214 TI - Homotopic connectivity in drug-naive, first-episode, early-onset schizophrenia. AB - BACKGROUND: The disconnection hypothesis of schizophrenia has been extensively tested in adults. Recent studies have reported the presence of brain disconnection in younger patients, adding evidence to support the neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in chronic and medicated patients, it has been extremely challenging for researchers to directly investigate abnormalities in the development of connectivity and their role in the pathophysiology of schizophrenia. The present study aimed to examine functional homotopy - a measure of interhemispheric connection - and its relevance to clinical symptoms in first-episode drug-naive early-onset schizophrenia (EOS) patients. METHODS: Resting-state functional magnetic resonance imaging was performed in 26 first-episode drug-naive EOS patients (age: 14.5 +/- 1.94, 13 males) and 25 matched typically developing controls (TDCs) (age: 14.4 +/- 2.97, 13 males). We were mainly concerned with the functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC). RESULTS: Early-onset schizophrenia patients exhibited both global and regional VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within the superior temporal cortex and postcentral gyrus. These interhemispheric synchronization deficits were negatively correlated with negative symptom of the Positive and Negative Syndrome Scale. Moreover, regions of interest analyses based on left and right clusters of temporal cortex and postcentral gyrus revealed abnormal heterotopic connectivity in EOS patients. CONCLUSIONS: Our findings provide novel neurodevelopmental evidence for the disconnection hypothesis of schizophrenia and suggest that these alterations occur early in the course of the disease and are independent of medication status. PMID- 25130218 TI - Ability to deliver services in Spanish: a survey of Michigan home health agencies, 2012. AB - The capacity of home health agencies to serve children from families with low English proficiency is not well understood. We conducted an exploratory survey of home health agencies in Michigan in 2012 to document whether they can provide services in Spanish, serve children, and accept Medicaid. PMID- 25130219 TI - Influence of education on HIV infection among pregnant women attending their antenatal care in Sekondi-Takoradi metropolis, Ghana. AB - This study investigated the influence of the level of education on HIV infection among pregnant women attending antenatal care in Sekondi-Takoradi, Ghana. A cross sectional study was conducted at four hospitals in the Sekondi-Takoradi metropolis. The study group comprised 885 consenting pregnant women attending antenatal care clinics. Questionnaires were administered and venous blood samples were screened for HIV and other parameters. Multivariable logistic regression analyses were performed to determine the association between the level of education attained by the pregnant women and their HIV statuses. The data showed that 9.83% (87/885) of the pregnant women were HIV seropositive while 90.17% (798/885) were HIV seronegative. There were significant differences in mean age (years) between the HIV seropositive women (27.45 +/- 5.5) and their HIV seronegative (26.02 +/- 5.6) counterparts (p = .026) but the inference disappeared after adjustment (p = .22). Multivariable logistic regression analysis revealed that pregnant women with secondary/tertiary education were less likely to have HIV infection compared with those with none/primary education (adjusted OR, 0.53; 95% CI, 0.30-0.91; p = .022). Our data showed an association with higher level of education and HIV statuses of the pregnant women. It is imperative to encourage formal education among pregnant women in this region. PMID- 25130220 TI - Post-traumatic stress symptoms among juvenile offenders in nigeria: implications for holistic service provisioning in juvenile justice administration. AB - BACKGROUND: There is hardly any study examining exposure to traumatic events and post-traumatic stress disorder (PTSD) among juvenile justice populations in Nigeria or any part of sub-Saharan Africa. METHOD: We examined the prevalence and trauma determinants of PTSD among a cohort of juvenile justice inmates in Nigeria, compared with a cohort of school-going adolescents. RESULTS: Ninety percent (90%) of the juvenile justice inmates reported exposure to at least one lifetime traumatic event with higher mean incident events, compared with 60% among the comparison group (p=.001). Juvenile justice inmates had significantly higher prevalence rate of current and lifetime PTSD than the comparison group (current: 5.8% vs. 1.4%; lifetime: 9.7% vs. 2.8%, p<.05). Mean incident traumatic event was statistically significantly higher among juvenile justice inmates who had PTSD. CONCLUSION: Posttraumatic stress symptoms are common among adolescents coming in contact with the juvenile justice system. Implications for holistic service provisioning in juvenile justice administration are discussed. PMID- 25130221 TI - Gendered inequalities within Ghana's National Health Insurance Scheme: are poor women being penalized with a late renewal policy? AB - This article addresses the implications of the mandatory delay in coverage for individuals residing in the Upper West Region (UWR) of Ghana who have dropped out of the National Health Insurance Scheme (NHIS) but later attempt to reenroll. Using data collected in 2011 in Ghana's UWR, we use a negative log-log model (n=1,584) to compare those who remain enrolled in the scheme with those who have dropped out. Women with unreliable incomes, who reported being food-insecure and those living with young children were more likely to drop out (OR range: 1.22 1.79, p<.05). Men, in contrast, were 50% more likely to drop out of the NHIS for being unsatisfied with services provided (OR range: 1.25-1.62, p<.01). Contrary to the original mandate of the NHIS, our study reveals clear gender differences in the factors contributing to dropouts, pointing to a bias in the impact of the block-out policy that is penalizing women for being poor. PMID- 25130222 TI - End-of-life treatment preference among low-income older adults: a race/ethnicity comparison study. AB - INTRODUCTION: Racial/ethnic minority older adults in low-income status might be at a greater risk than others of developing chronic illness. We sought to examine the effects of race/ethnicity on end-of-life (EOL) treatment preference among low income older adults. METHODS: A cross-sectional study surveyed 256 low-income older adults (90 Whites, 82 Hispanics, 84 Blacks) in a California city. RESULTS: Hierarchical multiple regression results showed that participants with greater religiosity (p < .01) or more frequent doctors' visits (p < .05) had greater preference for life-sustaining treatments during the final phase of life. Conversely, those with greater comfort about death (p < .01) or a belief that life and death are predestined (p < .05) preferred life-sustaining treatments less often. Race/ethnicity had no significant relationship with EOL treatment preference after accounting for other factors. CONCLUSION: Race/ethnicity encompasses multiple life contexts. Understanding the influences of both cultural beliefs and individual circumstances on EOL treatment preference is imperative. PMID- 25130223 TI - Unmet medical care and sexual health counseling needs-: a cross-sectional study among university students in Uganda. AB - In 2010, unmet medical care and sexual health counseling needs were assessed among students at a Ugandan University. Unmet medical care need was associated with poor mental health, experience of sexual coercion, and poor self-rated health. Unmet sexual health counseling need was significantly associated with being female, coming from an urban area, low social participation, poor mental health status, experience of sexual coercion, poor self-rated health, inconsistent condom use, and having multiple sexual partners. Gender differences, poor mental health, sexual coercion, poor self-rated health, and risky sexual behavior must be considered when designing intervention models to reduce unmet health care needs among young people in this setting. PMID- 25130225 TI - Definition and management of hypertension among Haitian immigrants: a qualitative study. AB - Hypertension is a major health concern among Haitian immigrants, one of the largest Caribbean immigrant groups in the United States. Yet, little is known about how Hatian immigrants define and manage hypertension. For this qualitative study, face-to-face semi-structured interviews were conducted with 31 Haitian immigrants in Miami Dade County, Florida. Results indicated that most Haitian immigrants used the Haitian Creole word tansyon to represent hypertension. Tansyon was considered as either a normal condition of the human body or a maladi (illness). Both traditional biomedical and alternative approaches were used to manage hypertension. The findings show that how Haitian immigrants defined hypertension shaped their beliefs about its occurrence and the resulting management strategies used. Those who believed tansyon was a normal body condition did not take any management measures. Awareness and understanding of Haitian immigrants' beliefs about and approaches to hypertension management can enhance culturally sensitive care and improve health outcomes. PMID- 25130224 TI - Barriers to HIV Testing in Black Immigrants to the U.S. AB - BACKGROUND: Late HIV testing is common among immigrants from sub Saharan Africa and the Caribbean. Since 2010, HIV testing is no longer a required component of immigrant screening examinations or mandatory for immigrants seeking long term residence in the US. Thus, barriers to HIV testing must be addressed. METHODS: Five hundred and fifty-five (555) immigrants completed a barriers-to-HIV testing scale. Univariate and multivariate linear regression were performed to examine predictors of barriers. RESULTS: In multivariate analysis, primary language other than English (beta=2.9, p=.04), lower education (beta=5.8, p=.03), low income [= below $20K/year] (beta=4.6, p=.01), no regular provider (beta=5.2, p=.002) and recent immigration (beta=5.7, p=.0008) were independently associated with greater barriers. Barriers due to health care access, privacy, fatalism, and anticipated stigma were greater for recent versus longer term immigrants. DISCUSSION: Immigrants from sub-Saharan Africa and the Caribbean face significant barriers to HIV testing. Interventions to improve access and timely entry into care are needed. PMID- 25130227 TI - Family gym: a model to promote physical activity for families with young children. AB - This report describes Family Gym, a family-centered model that (1) provides free access to physical activity for low-income families in the inner city; (2) targets young children (3-8 years) and their families; (3) engages families together in physical activity; and (4) stimulates social interaction among families. PMID- 25130226 TI - Promoting Chinese-speaking primary care physicians' communication with immigrant patients about colorectal cancer screening: a cluster randomized trial design. AB - Chinese Americans underutilize colorectal cancer screening. This study evaluated a physician-based intervention guided by social cognitive theory (SCT) to inform future research involving minority physicians and patients. Twenty-five Chinese speaking primary care physicians were randomized into intervention or usual care arms. The intervention included two 45-minute in-office training sessions paired with a dual-language communication guide detailing strategies in addressing Chinese patients' screening barriers. Physicians' feedback on the intervention, their performance data during training, and pre-post intervention survey data were collected and analyzed. Most physicians (~85%) liked the intervention materials but ~84% spent less than 20 minutes reading the guide and only 46% found the length of time for in-office training acceptable. Despite this, the intervention increased physicians' perceived communication self-efficacy with patients (p<.01). This study demonstrated the feasibility of enrolling and intervening with minority physicians. Time constraints in primary care practice should be considered in the design and implementation of interventions. PMID- 25130228 TI - Patching the safety net: establishing a free specialty care clinic in an academic medical center. AB - We describe the collaboration between an academic medical center and a free primary care clinic that provides multi-specialty services to indigent community members. Complementary components of both institutions have engendered a system in which they broaden the array of available services, providing a prototype for other institutions to consider. PMID- 25130229 TI - Exploring Protective factors among homeless youth: the role of natural mentors. AB - This study explored the presence and characteristics of natural mentors among 197 homeless youth and the association between natural mentoring relationships and youth functioning. Few studies have explored protective factors in the lives of homeless youth and how these may buffer against poor health outcomes. Relationships with natural mentors have been shown to have protective effects on adolescent functioning among the general adolescent population, and, thus, warrant further investigation with homeless youth. Results from this study revealed that 73.6% of homeless youth have natural mentoring relationships, split between kin and non-kin relationships. Having a natural mentor was associated with higher satisfaction with social support and fewer risky sexual behaviors. Findings suggest that natural mentors may play a protective role in the lives of homeless youth and should be considered an important source of social support that may enhance youth resilience. PMID- 25130230 TI - Health outcomes and retention in care following release from prison for patients of an urban post-incarceration transitions clinic. AB - Chronic health conditions are overrepresented among prisoners who often face barriers to medical care following release. Transitions clinics seek to provide timely access to medical care following release. This retrospective cohort study investigated care delivery and health outcomes for recently released prisoners receiving care at the Bronx Transitions Clinic. Among 135 recently released prisoners, median time from release to initial medical visit was 10 days (IQ Range: 5-31). Six-month retention in care was high for HIV-infection (86%), but lower for opioid dependence (33%), hypertension (45%) and diabetes (43%). At six months, 54% of HIV-patients had a suppressed viral load, but fewer buprenorphine treated patients reduced opioid use (19%), and fewer hypertensive and diabetic patients reached respective blood pressure (35%) and hemoglobin A1c (14%) goals. Access to medical care is necessary but not sufficient to control chronic health conditions. Additional interventions are necessary for formerly incarcerated people to achieve optimal health outcomes. PMID- 25130231 TI - Do our patients have enough to eat?: Food insecurity among urban low-income cancer patients. AB - This study assessed the prevalence and predictors of food insecurity among a cohort of underserved oncology patients at New York City cancer clinics. A demographic survey and the U.S. Household Food Security Survey Module were administered. A multivariate General Linear Model Analysis of Covariance was used to evaluate predictors of food insecurity. Four hundred and four (404) completed the surveys. Nearly one-fifth (18%) had very low, 38% low, 17% marginal, and 27% high food security. The Analysis of Covariance was statistically significant (F[7, 370] = 19.08; p < .0001; R-Square = 0.26). Younger age, Spanish language, poor health care access, and having less money for food since beginning cancer treatment were significantly associated with greater food insecurity. This cohort of underserved cancer patients had rates of food insecurity nearly five times those of the state average. More research is needed to understand better the causes and impact of food insecurity among cancer and chronic disease patients. PMID- 25130232 TI - Adverse childhood events: incarceration of household members and health-related quality of life in adulthood. AB - BACKGROUND: Incarceration of a household member has been associated with adverse outcomes for child well-being. METHODS: We assessed the association between childhood exposure to the incarceration of a household member and adult health related quality of life (HRQOL) in the 2009/2010 Behavioral Risk Factor Surveillance System controlling for age, race/ethnicity, education, and additional adverse childhood experiences. RESULTS: Adults who lived in childhood with an incarcerated household member had higher risk of poor HRQOL compared with adults who had not (adjusted relative risk [ARR] 1.18; 95% CI 1.07, 1.31). Among Black adults the association was strongest with the physical health component of HRQOL (ARR 1.58 [95% CI 1.18, 2.12]); among White adults, the association was strongest with the mental health component of HRQOL (ARR 1.29, [95% CI 1.07 1.54]). CONCLUSIONS: Living with an incarcerated household member during childhood is associated with higher risk of poor HRQOL during adulthood, suggesting that the collateral damages of incarceration for children are long term. PMID- 25130233 TI - "The stress will kill you": prisoner reentry as experienced by family members and the urgent need for support services. AB - The role of incarceration and community reentry after incarceration has been studied extensively for individual and community health; however, little attention has been given to the experiences of individuals who provide support to those in reentry. Through a community-academic partnership, seven focus groups were conducted with 39 individuals supporting a family member in reentry in the summer of 2012. The primary objectives of the focus groups were to explore community experiences and perspectives regarding providing support during a family member's reentry from a period of incarceration and any desired support for themselves during this time. Five themes emerged under a metatheme of stress, indicating that family members experience acute stress as a result of family reentry that adds to the chronic stress they already endure. Programs that acknowledge the difficult role of family members as supporters during an individual's reentry and provide support to them are desperately needed. PMID- 25130234 TI - Psychiatric disorders, high-risk behaviors, and chronicity of episodes among predominantly African American homeless Chicago youth. AB - OBJECTIVE: This cross-sectional study investigated the relationships between psychiatric and substance-related disorders, high-risk behaviors, and the onset, duration, and frequency of homelessness among homeless youth in Chicago. METHODS: Sixty-six homeless youth were recruited from two shelters in Chicago. Demographic characteristics, psycho-pathology, substance use, and risk behaviors were assessed for each participant. RESULTS: Increased frequency and duration of homeless episodes were positively correlated with higher rates of psychiatric diagnoses. Increased number of psychiatric diagnoses was positively correlated with increased high-risk behaviors. Participants with diagnoses of Current Suicidality, Manic Episodes, Obsessive Compulsive Disorder, Substance Abuse, and Psychotic Disorder had a higher chronicity of homelessness than those without diagnoses. CONCLUSIONS: Significant differences were evident between the three time parameters, suggesting that stratification of data by different time variables may benefit homelessness research by identifying meaningful subgroups who may benefit from individualized interventions. PMID- 25130235 TI - Substance use, risk of dependence, counseling and treatment among adult health center patients. AB - Health centers provide primary care to 20 million underserved patients. We examined the prevalence of substance use and risk of dependence among health center patients, and identified factors associated with desire for counseling/treatment and discussions about substance use with a doctor. National data on 3,949 adults came from the 2009 Health Center Patient Survey. Forty percent of patients reported past-year binge drinking, 14% of patients had used any drug in the past three months, and 13% of these recent users were at high risk of dependence. Eighty-four percent of patients who desired substance use counseling or treatment reported receiving it. Several factors were associated with patients discussing substance use with their doctors (e.g., younger age, being male, severe mental illness, current smoking). Patients most likely to desire substance use counseling or treatment were male, unmarried, insured, current smokers, and indicated mental health problems. PMID- 25130236 TI - Homelessness and risk of end-stage renal disease. AB - To identify homeless people with chronic kidney disease (CKD) who were at highest risk for end-stage renal disease (ESRD), we studied 982 homeless and 15,674 domiciled people with CKD receiving public health care. We developed four risk prediction models for the primary outcome of ESRD. Overall, 71 homeless and 888 domiciled people progressed to ESRD during follow-up (median: 6.6 years). Homeless people with CKD experienced significantly higher incidence rates of ESRD than poor but domiciled peers. Most homeless people who developed progressive CKD were readily identifiable well before ESRD using a prediction model with five common variables. We estimated that program following homeless people in the highest decile of ESRD risk would have captured 64-85% of those who eventually progressed to ESRD within five years. Thus, an approach targeting homeless people at high risk for ESRD appears feasible and could reduce substantial morbidity and costs incurred by this highly vulnerable group. PMID- 25130237 TI - The impact of obesity on medication use and expenditures among nonelderly adults with asthma. AB - Obesity contributes substantially to health resource use and costs. This study examines the impact of obesity on medication use and expenditures among nonelderly adults with asthma using the Medical Expenditure Panel Survey. Obese classes II/III individuals were more likely to have current asthma, seek treatment for asthma, use more medications, and have higher medication and health care expenditures compared with normal weight individuals. Multivariate results indicate that if obese classes II/III were normal weight the probability of asthma treatment would decrease by 8.0 percentage points. Conditional on any asthma treatment, if obese classes II/III were normal weight the mean number of total prescribed medications would decrease by 19.42 fills, and expected expenditures on total prescribed medications and health care would decrease by $1,738.68 and $3,682.58, respectively. These results suggest that, all else equal, reduction in body weight may help reduce health resource use and expenditures for nonelderly adults with asthma. PMID- 25130238 TI - Affecting African American men's prostate cancer screening decision-making through a mobile tablet-mediated intervention. AB - African American men experience a 60% higher incidence of prostate cancer and are more than twice as likely to die from it than White men. Evidence is insufficient to conclude that definitively screening for prostate cancer reduces the likelihood of morbidity or death. Patients are encouraged to discuss screening alternatives with health care providers for informed decision-making (IDM). The extent of IDM in clinical or community setting is not known. This study uses data from a community-based, computer-mediated, IDM intervention that targeted 152 African American aged 40 to 70. Pretest-posttest differences in means for prostate cancer knowledge, screening decisional conflict, and screening decisional self-efficacy were examined by two-tailed t-tests. Overall, the intervention significantly improved respondents' prostate cancer knowledge (p<.0001), significantly improved decisional self-efficacy (p<.0001) and significantly reduced decisional conflict (p<.0001). Specifically, the intervention significantly promoted IDM among men who reported more education, being married, having financial resources, and younger age. PMID- 25130240 TI - Structural vulnerability and problem drinking among Latino migrant day laborers in the San Francisco Bay Area. AB - Latino migrant day laborers (LMDLs) live under challenging conditions in the San Francisco Bay Area. This study explored day laborer alcohol use guided by a structural vulnerability framework, specifically problem vs. non-problem drinking as perceived by LMDLs and how they cope with or try to avoid problem drinking given their broader environment. The study utilized ethnographic methods including in-depth semi-structured qualitative interviews with 51 LMDLs. Findings revealed the considerable challenge of avoiding problem drinking given socio environmental factors that influence drinking: impoverished living and working conditions, prolonged separation from home and family, lack of work authorization, consequent distress and negative mood states, and peer pressure to drink. While participants shared strategies to avoid problem drinking, the success of individual-level efforts is limited given the harsh structural environmental factors that define day laborers' daily lives. Discussed are implications for prevention and intervention strategies at the individual, community, national and international levels. PMID- 25130239 TI - Trust in health care providers: factors predicting trust among homeless veterans over time. AB - We examined whether a combination of predisposing, enabling, need, and primary care experience variables would predict trust in medical health care providers for homeless veterans over 18 months. Linear mixed model analysis indicated that, among these variables, race, social support, service-connected disability status, and satisfaction and continuity with providers predicted trust in provider over time. Trust in providers improved during the initial stages of the relationship between patient and provider and then declined to slightly below baseline levels over time. Further research is needed to determine generalizability and effects of provider trust on patient health care status over longer periods of time. PMID- 25130242 TI - Injectable Contraceptive Continuation among Female Exotic Dancers Seeking Mobile Reproductive Health Services. AB - OBJECTIVES: We describe depot medroxyprogesterone acetate (DMPA) continuation patterns among female exotic dancers receiving reproductive health services at a mobile syringe exchange. METHODS: Clients initiating DMPA between November 2009 and August 2012 were identified retrospectively via chart review. Life table analysis measured continuation. Client characteristics were compared using chi square tests. RESULTS: Sixty nine clients were identified; 72% were African American and 63% were younger than 25. At three months, 36% of the study sample continued DMPA; those continuing were more likely to be White (p=0.01) and receive other services (p=.01). The 12-month cumulative continuation probability was 0.09. Considering those who had received an injection, continuation proportions were higher (46% at 6; 71% at 12 months). CONCLUSIONS: A subset of female exotic dancers may favor DMPA as a long term contraceptive. Integrating mobile reproductive health services into public health programs can help fulfill the unique health needs of this high-risk population. PMID- 25130241 TI - Contraceptive implant knowledge and practices of providers serving an urban, low income community. AB - Contraceptive implants are highly effective but infrequently used by low-income women, who are at high risk of unintended pregnancy. Provider factors that may affect implant acceptance merit further exploration. We surveyed 66 clinicians serving an urban, low-income community from adult primary care, women's health, and adolescent practices. We assessed implant education, knowledge, perceptions of accessibility and cost, and patient selection practices. Education about implants varied from 15% in adult primary care to 30% in adolescent practice and 75% in women's health. Among women's health providers, 54% were trained to insert implants. Despite having eligible candidates, some providers were unlikely to recommend implants to patients who are nulliparous (8%), teens (22%), depressed (24%) or obese (22%). Forty-one percent of providers reported insertion wait times of at least three weeks. Among low-income women, deficits in provider education, restrictive practice patterns, and long insertion wait times may affect contraceptive implant use. PMID- 25130243 TI - African American male and female student perceptions of Pulvers Body Images: implications for obesity, health care, and prevention. AB - Differences in male and female perception response to the Pulvers Body Image Scale (PBIS) were examined among 356 freshmen African American students attending an urban historically Black college/university (HBCU). Participants completed a questionnaire identifying images that best represented their current, healthy, and ideal body image. Compared with males, more females selected the normal body image as their ideal (63.3% vs. 15.3%) and healthy body shape (59.3% vs. 15.3%) (p<.001). Compared with females, more males selected the overweight body image as their ideal (44.6% vs. 30.2%) and healthy body shape (52.2% vs. 36.2%) (p<.01). Similarly, more males selected the obese body image as their ideal (40.1% vs. 6.5%) and healthy body shape (32.5% vs. 4.5%) compared with females (p<.001). Male freshmen at an HBCU perceive a larger body image as healthy and ideal more often than their female counterparts, thereby increasing the potential for their weight-related health risks. PMID- 25130244 TI - Are female college students who are diagnosed with depression at greater risk of experiencing sexual violence on college campus? AB - We examined the association between depression and sexual violence among 18-24 year-old female college students using National College Health Assessment survey. Data were collected from a nationally representative sample of 10,541 female students on 33 college campuses. Results showed that female students who were reportedly ever diagnosed with depression were 1.56 times more likely than those who had never been diagnosed with depression to have experienced sexual violence. Female students who had one or more sexual partners currently were found 3.17 times more likely than those who had no sexual partner to have experienced sexual violence; similarly, female students who engaged in binge drinking in the previous two weeks were found about two times more likely than their counterparts to have experienced sexual violence. Depression is a public health issue and must be addressed sooner rather than later in order to reduce and prevent sexual violence on college campuses. PMID- 25130246 TI - Medicare eligibility age, health disparities, and medicare reform. AB - Medicare eligibility age is a major focus of health policy discussions about how to tackle increasing health care costs and reduce the national debt. Raising the Medicare eligibility age from 65 to 67 would presumably reduce the cost of Medicare, but the opponents caution it could exacerbate health disparities by race and/or income. We compared the mortality rate, hospitalization rate, and annual Medicare expenditures of current White and Black Medicare beneficiaries at age 65-66 years using the Medicare Current Beneficiary Survey. We found Blacks have higher health care demand reimbursed by Medicare than Whites at these ages. To raise the Medicare eligibility age from 65 to 67 would likely have more negative health and economic effects among Blacks than among Whites, and would likely exacerbate health disparities by race. We suggest great caution when considering this policy option. PMID- 25130247 TI - Hospital practices in the collection of patient race, ethnicity, and language data: a statewide survey, California, 2011. AB - California mandates hospitals to collect and report patient race, ethnicity, and primary spoken language (REL). A lack of specific guidelines and standardized practices on how data should be collected has contributed to inconsistent and incomplete data.General acute care hospitals in California completed a survey to elucidate practices regarding collection and auditing of patient REL. Nearly all hospitals reported collecting race and/or ethnicity (97%). The majority of hospitals used standardized forms for collection, and 75% audited patient information for completeness. Popular accepted strategies to improve the quality and completeness of REL included collecting data at the first encounter, routine staff training, incorporating REL questions into existing admissions forms, and developing and enforcing hospital policies regarding data collection.California hospitals are collecting information on patient REL as mandated, but variation in data collection exists. Hospitals endorse many reasonable approaches for standardization, and may benefit from standardized data collection and auditing practices. PMID- 25130245 TI - HIV testing and engagement in care among highly vulnerable female sex workers: implications for treatment as prevention models. AB - BACKGROUND: Although emerging Treatment as Prevention models can be effective in reducing HIV incidence among high-risk populations, many HIV infected individuals remain undiagnosed or fail to engage in HIV care. METHODS: This study examined the factors associated with HIV testing and care among a population of substance using female sex workers. RESULTS: Recent HIV testing was associated with higher education level, having a regular health care provider or clinic, recent crack use, and higher sexual risk behaviors; HIV treatment utilization was associated with higher levels of social support, having a regular health care provider or clinic, housing stability and insurance coverage. Qualitative data revealed HIV related stigma, denial, social isolation, and substance use as barriers to HIV testing and treatment; social support and accessibility of services were key enablers. CONCLUSIONS: Improving HIV testing and linkage to treatment among female sex workers will require structural initiatives to reduce stigma and increase service seeking support. PMID- 25130249 TI - Race/ethnicity and other social determinants of psychological well-being and functioning in mental health clinics. AB - Significant racial and ethnic differences exist in the receipt of psychiatric care and help-seeking. We examined the relationship between race/ethnicity and psychological well-being and functioning in psychiatric outpatients. We analyzed intake data for 8,697 adult patients in psychiatry clinics in New England between 2008 and 2010. Patients rated psychological wellbeing using the Schwartz Outcome Scale (SOS-10); clinicians rated the Global Assessment of Functioning (GAF). In an analysis of variance with covariates, race/ethnicity exhibited a small but statistically significant association with GAF (F(4,8481)=17.902, p<.001) and SOS 10 scores (F(4,8165)=7.271, p<.001). However, after adjustment for physical health and socioeconomic variables, these differences became insignificant or were reversed. Our findings suggest that the relationship between race/ethnicity and mental health may be confounded by other socioeconomic or health differences and may be small compared with the effect of those variables. Future studies on race and psychological well-being should take social determinants of health into consideration. PMID- 25130248 TI - The development of the DSM-5 Cultural Formulation Interview-Fidelity Instrument (CFI-FI): a pilot study. AB - This paper reports on the development of the Cultural Formulation Interview Fidelity Instrument (CFI-FI) which assesses clinician fidelity to the DSM-5 Cultural Formulation Interview (CFI). The CFI consists of a manualized set of standard questions that can precede every psychiatric evaluation. It is based on the DSM-IV Outline for Cultural Formulation, the cross-cultural assessment with the most evidence in psychiatric training. Using the New York sample of the DSM-5 CFI field trial, two independent raters created and finalized items for the CFI FI based on six audio-taped and transcribed interviews. The raters then used the final CFI-FI to rate the remaining 23 interviews. Inter-rater reliability ranged from .73 to 1 for adherence items and .52 to 1 for competence items. The development of the CFI-FI can help researchers and administrators determine whether the CFI has been implemented with fidelity, permitting future intervention research. PMID- 25130251 TI - Opting to opt-in: policy choice, program expectations and results in West Virginia's Medicaid reform initiative. AB - Following the passage of the Federal Deficit Reduction Act in 2005, a few states, including West Virginia, redesigned their Medicaid programs to emphasize personal responsibility and consumer-driven health decisions. The West Virginia program was implemented in 2006 and was subsequently abandoned in 2010 due to changes in Federal laws and continuing criticism by advocacy groups whose expectations for enrollment in a wellness-based plan were not met. Using the results of a survey of the West Virginia members, the authors explore the public policy and implementation factors of this program. We argue that initial policy design relied on existing implementation mechanisms, while it needed specific tactics to address the novelty of the choice members were facing. With the passage of the Patient Protection and Affordable Care Act, the West Virginia results provide valuable insights for future health reform policy implementation, especially as they relate to consumer-directed health decision-making and the role of intermediaries who can play a role in assisting consumers in their choices. PMID- 25130250 TI - The pattern of association between U.S. economic indicators and infant mortality rates at the state level. AB - This cross-sectional ecological study examines the pattern of association of state income and income inequality (measured by Gini coefficient) with state infant mortality rates (IMRs) in the U.S. Scatter plots and correlation coefficients were used to examine bivariate associations and bubble plots to examine three-way relationships. Infant mortality rate was positively associated with Gini (R=0.397, p=.004) and negatively with income (R=-0.482, p <.001). However using Black and White IMRs, the associations with Gini were non significant, but with income remained significant. The bubble plot of Gini versus White IMR (income represented by bubble size) showed increasing IMR as Gini increases and income decreases, except for a subgroup of high-gini, high-income states with low IMRs. State income appears to be a stronger and more consistent predictor of U.S. IMRs for both Black and White races and can explain the pattern of association of White IMR with state Gini coefficient. PMID- 25130254 TI - Ag2S-hollow Fe2O3 nanocomposites with NIR photoluminescence. AB - A facile synthesis of Ag2S-hollow Fe2O3 nanocomposites with NIR photoluminescence was firstly demonstrated by the sulfidation of Ag-Fe2O3 core-shell nanoparticles. Characteristic morphology transformations along with color changes were recorded and a mechanism was proposed for the sulfidation process, which can provide new possibilities to fabricate other complex nanostructures. PMID- 25130255 TI - Case of radioactive iodine exposure during pregnancy. AB - A 43-year-old woman (gravida 0, para 0) was diagnosed with thyroid carcinoma and had been receiving radioactive iodine for remnant ablation. Eventually, her pregnant status became apparent; during radiation, she was at 5 gestational weeks. She decided to continue the pregnancy and delivered a boy of 2362 g at 37 gestational weeks. The infant did not present thyroid dysfunction or developmental abnormalities at 2 months of age. The patient was in the early pregnancy stage during radiation, so the fetus did not develop radiation-related damage of the thyroid gland because at this stage, the fetal thyroid does not concentrate iodine. Although the mother had received radioactive iodine during the critical organogenesis period, the fetus did not develop teratogenicity because the radiation was administered at the borderline threshold for teratogenicity. This case suggests the importance of iodine thyroid absorption when considering radiation-related damage to the fetal thyroid gland during early pregnancy. PMID- 25130257 TI - WITHDRAWN: Laparoscopic surgery for pelvic pain associated with endometriosis. PMID- 25130256 TI - Vertical inhibition of the MAPK pathway enhances therapeutic responses in NRAS mutant melanoma. AB - The MEK inhibitor MEK162 is the first targeted therapy agent with clinical activity in patients whose melanomas harbor NRAS mutations; however, median PFS is 3.7 months, suggesting the rapid onset of resistance in the majority of patients. Here, we show that treatment of NRAS-mutant melanoma cell lines with the MEK inhibitors AZD6244 or trametinib resulted in a rebound activation of phospho-ERK (pERK). Functionally, the recovery of signaling was associated with the maintenance of cyclin-D1 expression and therapeutic escape. The combination of a MEK inhibitor with an ERK inhibitor suppressed the recovery of cyclin-D1 expression and was associated with a significant enhancement of apoptosis and the abrogation of clonal outgrowth. The MEK/ERK combination strategy induced greater levels of apoptosis compared with dual MEK/CDK4 or MEK/PI3K inhibition across a panel of cell lines. These data provide the rationale for further investigation of vertically co-targeting the MAPK pathway as a potential treatment option for NRAS-mutant melanoma patients. PMID- 25130258 TI - WITHDRAWN: Laparoscopic surgery for subfertility associated with endometriosis. PMID- 25130260 TI - Mechanistic aspects of thioflavin-T self-aggregation and DNA binding: evidence for dimer attack on DNA grooves. AB - Thioflavin-T (TFT) is a fluorescent marker widely employed in biomedical research but the mechanism of its binding to polynucleotides has been poorly understood. This paper presents a study of the mechanisms of TFT self-aggregation and binding to DNA. Relaxation kinetics of TFT solutions show that the cyanine undergoes dimerization followed by dimer isomerisation. The interaction of TFT with DNA has been investigated using static methods, such as spectrophotometric and spectrofluorometric titrations under different conditions (salt content, temperature), fluorescence quenching, viscometric experiments and the T-jump relaxation method. The combined use of these techniques enabled us to show that the TFT monomer undergoes intercalation between the DNA base pairs and external binding according to a branched mechanism. Moreover, it has also been observed that, under dye excess conditions, the TFT dimer binds to the DNA grooves. The molecular structures of intercalated TFT and the groove-bound TFT dimer are obtained by performing QM/MM MD simulations. PMID- 25130261 TI - Reactivity of cosmetic UV filters towards skin proteins: model studies with Boc lysine, Boc-Gly-Phe-Gly-Lys-OH, BSA and gelatin. AB - OBJECTIVE: Organic UV filters are used as active ingredients in most sunscreens and also in a variety of daily care products. Their good (photo) stability is of special interest to guarantee protective function and to prevent interactions with the human skin. Due to the mostly electrophilic character of the UV filters, reactions with nucleophilic protein moieties like lysine side chains are conceivable. Prior studies showed that the UV filters octocrylene (OCR), butyl methoxydibenzoylmethane (BM-DBM), ethylhexyl salicylate (EHS), ethylhexyl methoxycinnamate (EHMC), benzophenone-3 (BP-3), ethylhexyl triazone (EHT) and dibenzoylmethane (DBM) were able to covalently bind to an HPTLC amino phase and the amino acid models ethanolamine and butylamine after slightly heating and/or radiation. METHODS: Boc-protected lysine, the tetrapeptide Boc-Gly-Phe-Gly-Lys OH, bovine serum albumin (BSA) and porcine gelatin were used as more complex models to determine the reactivity of the mentioned UV filters towards skin proteins under thermal or UV irradiation conditions. RESULTS: After gentle heating at 37 degrees C, benzophenone imines were identified as reaction products of BP-3 and OCR with Boc-lysine and the tetrapeptide, whereas DBM and BM-DBM yielded enamines. For EHMC, a Michael-type reaction occurred, which resulted in addition of Boc-lysine or the tetrapeptide to the conjugated double bond. Ester aminolysis of EHS and EHT mainly afforded the corresponding amides. Reactions of the UV filters with BSA changed the UV spectrum of BSA, generally associated with an increase of the absorption strength in the UVA or UVB range. For all protein models, the UV filters showed an increasing reactivity in the order EHT < EHMC < EHS < BP-3 < OCR < DBM < BM-DBM. CONCLUSION: Especially the UV absorbers BM-DBM, OCR and BP-3, which are seen as common allergens or photoallergens, showed a high reactivity towards the different skin protein models. As the formation of protein adducts is recognized as important key element in the induction of skin sensitization, the results of this study can contribute to a better understanding of the underlying chemical mechanisms of such reactions. PMID- 25130259 TI - Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis. AB - Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells. PMID- 25130263 TI - Drought effect on plant nitrogen and phosphorus: a meta-analysis. AB - Climate change scenarios forecast increased aridity in large areas worldwide with potentially important effects on nutrient availability and plant growth. Plant nitrogen and phosphorus concentrations (plant [N] and [P]) have been used to assess nutrient limitation, but a comprehensive understanding of drought stress on plant [N] and [P] remains elusive. We conducted a meta-analysis to examine responses of plant [N] and [P] to drought manipulation treatments and duration of drought stress. Drought stress showed negative effects on plant [N] (-3.73%) and plant [P] (-9.18%), and a positive effect on plant N:P (+ 6.98%). Drought stress had stronger negative effects on plant [N] and [P] in the short term (< 90 d) than in the long term (> 90 d). Drought treatments that included drying-rewetting cycles showed no effect on plant [N] and [P], while constant, prolonged, or intermittent drought stress had a negative effect on plant [P]. Our results suggest that negative effects on plant [N] and [P] are alleviated with extended duration of drought treatments and with drying-rewetting cycles. Availability of water, rather than of N and P, may be the main driver for reduced plant growth with increased long-term drought stress. PMID- 25130262 TI - Youth depression alleviation: the Fish Oil Youth Depression Study (YoDA-F): A randomized, double-blind, placebo-controlled treatment trial. AB - AIM: US authorities have recommended 'black-box' warnings for antidepressants because of the increased risk of suicidality for individuals up to age 25. There is thus a clinical and ethical imperative to provide effective treatment for youth depression with an acceptable risk-benefit balance. Long-chain omega-3 polyunsaturated fatty acids (PUFAs) play an important role in a range of physiological processes in living organisms. Supplementation with omega-3 PUFAs has been shown to have a range of beneficial effects on both physical and mental health, and results of previous trials suggest that omega-3 PUFAs may be a safe and effective treatment for depression. However, conclusions from these trials have been limited by their relatively small sample sizes. METHODS: This trial will test the effectiveness of a 12-week parallel group, double-blind, randomized, placebo-controlled trial of 1.4 g day(-1) omega-3 PUFAs in help seeking 15- to 25-year-olds (N = 400) presenting with major depressive disorder. The primary hypothesis is that young people will show greater improvement of depressive symptoms after 12 weeks of treatment with omega-3 PUFAs plus cognitive behavioural case management compared with treatment with placebo plus cognitive behavioural case management. CONCLUSION: Because of using a large sample, results from this study will provide the strongest evidence to date to inform the use of omega-3 PUFAs as first-line therapy in young people presenting with major depressive disorder. The study also heralds an important step towards indicated prevention of persistent depression, which may reduce the burden, stigmatization, disability and economic consequences of this disorder. PMID- 25130264 TI - Use of porcine luteinizing hormone at oestrous onset in a protocol for fixed-time artificial insemination in gilts. AB - The aim of this study was to evaluate the effect of porcine luteinizing hormone (pLH) given at oestrous onset in gilts, by different routes and doses, on the interval between onset of oestrus and ovulation (IOEO) and reproductive performance using a single fixed-time artificial insemination (FTAI). A total of 153 gilts were submitted to oestrous detection at 8-h intervals and assigned to three groups: control - without hormone application and inseminated at 0, 24 and 48 h after oestrous onset; VS2.5FTAI - 2.5 mg pLH by the vulvar submucosal route at oestrous onset and a single FTAI 16 h later; IM5FTAI - 5 mg pLH by the intramuscular route at oestrous onset and a single FTAI 16 h later. More VS2.5FTAI gilts (47.1%; p < 0.05) ovulated within 24 h after oestrous onset than control gilts (25.5%) whereas IM5FTAI gilts had an intermediate percentage (31.4%; p > 0.05). The IOEO tended to be shorter (p = 0.06) in VS2.5FTAI (30.2 +/ 1.4 h) than in control (34.7 +/- 1.4 h) gilts, but there was no difference (p > 0.05) between control and IM5FTAI (32.8 +/- 1.4 h) gilts. Farrowing rate was not different (p > 0.05) among treatments. Total born piglets (TB) was lower (p < 0.05) in VS2.5FTAI (12.3 +/- 0.4) than in control gilts (14.1 +/- 0.4), whereas intermediate TB was observed in IM5FTAI gilts (13.3 +/- 0.4). Due to the advancement of ovulation, reduction of the hormonal dose and the ease of application, the vulvar submucosal route would be the best option for FTAI protocols, but their negative impact on litter size remains to be elucidated. Taking into account the good fertility results obtained in IM5FTAI gilts whose ovulation was not advanced, the possibility of a single FTAI without any hormonal treatment should be further investigated, to establish reliable FTAI protocols for gilts. PMID- 25130266 TI - Sublingual immunotherapy alters expression of IL-4 and its soluble and membrane bound receptors. AB - Seasonal allergic rhinitis (SAR) is a disease of increasing prevalence, which results from an inappropriate T helper cell, type 2 (Th2) response to pollen. Specific immunotherapy (SIT) involves repeated treatment with small doses of pollen and can result in complete and lasting reversal of SAR. Here, we assayed the key Th2 cytokine, IL-4, and its soluble and membrane-bound receptor in patients with SAR before and after SIT. Using allergen-challenge assays, we found that SIT treatment decreased IL-4 cytokine levels, as previously reported. We also observed a significant decrease in the IL-4 membrane-bound receptor (mIL4R) at the level of both mRNA and protein. SIT treatment resulted in a significant increase in the inhibitory soluble IL-4 receptor (sIL4R). Reciprocal changes in mIL4R and sIL4R were also observed in patient serum. Altered mIL4R and sIL4R is a novel explanation for the positive effects of immunotherapy with potential basic and clinical research implications. PMID- 25130265 TI - The association between depressive symptoms from early to late adolescence and later use and harmful use of alcohol. AB - Depressive symptoms and alcohol misuse contribute substantially to the global health burden. These phenotypes often manifest, and frequently co-occur, during adolescence. However, few studies have examined whether both baseline levels of depressive symptoms and change in symptoms are associated with alcohol outcomes. In addition, inconsistent findings could be due to sex differences or the use of different alcohol outcomes. Using data from a prospective population-based cohort in the UK, we estimated trajectories of depressive symptoms from 12 years 10 months to 17 years 10 months, separately for male and female participants. We assessed whether baseline and change in depressive symptoms were associated with use and harmful use of alcohol at 18 years 8 months. Among females, increasing depressive symptoms were associated with increased alcohol use; whilst for males, there was little evidence of this. When examining harmful levels of alcohol use, baseline levels of depressive symptoms in males were weakly related to later harmful alcohol use but this association was attenuated substantially through adjustment for confounders. In contrast, both baseline symptoms and increase in symptoms were associated with later harmful alcohol use in females and these associations were not diminished by confounder adjustment. Elevated depressive symptoms during adolescence are positively associated with increases in both use and harmful use of alcohol at 18 years 8 months. These findings differ between the sexes. Further research is needed to examine the mechanisms underlying the link between depressive symptoms and harmful alcohol use to identify potentially modifiable factors for intervention. PMID- 25130268 TI - Bone loss and fractures in limbs paralyzed by spinal cord injury: Prevention, diagnosis, and treatment. PMID- 25130269 TI - Reflections on the enduring value of critical scholarship. PMID- 25130267 TI - Quantitative relations between the eyeball, the optic nerve, and the optic canal important for intracranial pressure monitoring. AB - OBJECTIVE: To find correlations between diameters of the optic nerve sheath (ONSD), the eyeball, and the optic canal that might be important for intracranial pressure monitoring. METHODS: In a prospective cohort study, the CT data of consecutive 400 adults (18+) with healthy eyes and optic nerves and absence of neurological diseases were collected and analyzed. When the CT scans were obtained, the diameters of the optic nerve sheath, the eyeball, and the optic canal were measured and statistically analyzed. The data obtained from the left and from the right eyeballs and optic nerves were compared. The correlation analysis was performed within these variables, with the gender, and the age. RESULTS: In healthy persons, the ONSD varies from 3.65 mm to 5.17 mm in different locations within the intraorbital space with no significant difference between sexes and age groups. There is a strong correlation between the eyeball transverse diameter (ETD) and ONSD that can be presented as ONSD/ETD index. In healthy subjects, the ONSD/ETD index equals 0.19. CONCLUSION: The calculation of an index when ONSD is divided by the ETD of the eyeball presents precise normative database for ONSD intracranial pressure measurement technique. When the ONSD is measured for intracranial pressure monitoring, the most stable results can be obtained if the diameter is measured 10 mm from the globe. These data might serve as a normative database at emergency departments and in general neurological practice. PMID- 25130270 TI - Image analysis of skin color heterogeneity focusing on skin chromophores and the age-related changes in facial skin. AB - BACKGROUND/PURPOSE: Heterogeneity with respect to skin color tone is one of the key factors in visual perception of facial attractiveness and age. However, there have been few studies on quantitative analyses of the color heterogeneity of facial skin. The purpose of this study was to develop image evaluation methods for skin color heterogeneity focusing on skin chromophores and then characterize ethnic differences and age-related changes. METHODS: A facial imaging system equipped with an illumination unit and a high-resolution digital camera was used to develop image evaluation methods for skin color heterogeneity. First, melanin and/or hemoglobin images were obtained using pigment-specific image-processing techniques, which involved conversion from Commission Internationale de l'Eclairage XYZ color values to melanin and/or hemoglobin indexes as measures of their contents. Second, a spatial frequency analysis with threshold settings was applied to the individual images. Cheek skin images of 194 healthy Asian and Caucasian female subjects were acquired using the imaging system. Applying this methodology, the skin color heterogeneity of Asian and Caucasian faces was characterized. RESULTS: The proposed pigment-specific image-processing techniques allowed visual discrimination of skin redness from skin pigmentation. In the heterogeneity analyses of cheek skin color, age-related changes in melanin were clearly detected in Asian and Caucasian skin. Furthermore, it was found that the heterogeneity indexes of hemoglobin were significantly higher in Caucasian skin than in Asian skin. CONCLUSION: We have developed evaluation methods for skin color heterogeneity by image analyses based on the major chromophores, melanin and hemoglobin, with special reference to their size. This methodology focusing on skin color heterogeneity should be useful for better understanding of aging and ethnic differences. PMID- 25130271 TI - Hsp27 regulates EGF/beta-catenin mediated epithelial to mesenchymal transition in prostate cancer. AB - Increased expression of the molecular chaperone Hsp27 is associated with the progression of prostate cancer (PCa) to castration-resistant disease, which is lethal due to metastatic spread of the prostate tumor. Metastasis requires epithelial to mesenchymal transition (EMT), which endows cancer cells with the ability to disseminate from the primary tumor and colonize new tissue sites. A wide variety of secreted factors promote EMT, and while overexpression and constitutive activation of epidermal growth factor (EGF) signaling is associated with poor prognosis of PCa, a precise role of EGF in PCa progression to metastasis remains unclear. Here, we show that Hsp27 is required for EGF-induced cell migration, invasion and MMPs activity as well as the expression of EMT markers including Fibronectin, Vimentin and Slug with concomitant decrease of E cadherin. Mechanistically, we found that Hsp27 is required for EGF-induced AKT and GSK3beta phosphorylation and beta-catenin nuclear translocation. Moreover, silencing Hsp27 decreases EGF dependent phosphorylation of beta-catenin on tyrosine 142 and 654, enhances beta-catenin ubiquitination and degradation, prevents beta-catenin nuclear translocation and binding to the Slug promoter. These data suggest that Hsp27 is required for EGF-mediated EMT via modulation of the beta-catenin/Slug signaling pathway. Together, our findings underscore the importance of Hsp27 in EGF induced EMT in PCa and highlight the use of Hsp27 knockdown as a useful strategy for patients with advanced disease. PMID- 25130272 TI - Cochlear implantation in children with bacterial meningitic deafness: The influence of the degree of ossification and obliteration on impedance and charge of the implant. AB - OBJECTIVES: To determine impedance values and charge consumption following cochlear implantation post-meningitic deaf children depending on the grade of cochlear ossification and obliteration. METHODS: Post-meningitic deaf (n=49) and control (n=43) children treated with cochlear implants were included in the study. Impedance and charge values were calculated for each group. The degree of ossification of the cochlea was evaluated from a high-resolution computed tomography (HRCT) scan whereas the degree of obliteration was determined intraoperatively by the surgeon. RESULTS: Pneumococci were the principal pathogen responsible for bacterial meningitis, followed by meningococci. In HRCT scans, the degree of ossification was 1 and 2 in 29% of patients. The results of the intraoperative assessment of the cochlea showed obliteration grade 1 in 38% and grade 2 in 23% of cases. Children in the meningitis group showed significant higher impedances comparing to the control group. A significantly increased charge consumption was observed in patients with a grade 2 ossification when compared to those without ossification (P=0.02). Discussion Cochlea implanted children with meningitis-related deafness exhibit higher impedances, especially in the region of the basal and middle turn, however, not depending on the degree of cochlear ossification. High impedances and charge in the meningitis group may be explained by alterations in the central auditory pathway or on the electrode surface. CONCLUSION: To optimize the outcome in post-meningitic deaf children, surgery is advisable at an early stage prior to the onset of cochlear ossification. PMID- 25130273 TI - The yeast oligopeptide transporter Opt2 is localized to peroxisomes and affects glutathione redox homeostasis. AB - Glutathione, the most abundant small-molecule thiol in eukaryotic cells, is synthesized de novo solely in the cytosol and must subsequently be transported to other cellular compartments. The mechanisms of glutathione transport into and out of organelles remain largely unclear. We show that budding yeast Opt2, a close homolog of the plasma membrane glutathione transporter Opt1, localizes to peroxisomes. We demonstrate that deletion of OPT2 leads to major defects in maintaining peroxisomal, mitochondrial, and cytosolic glutathione redox homeostasis. Furthermore, ?opt2 strains display synthetic lethality with deletions of genes central to iron homeostasis that require mitochondrial glutathione redox homeostasis. Our results shed new light on the importance of peroxisomes in cellular glutathione homeostasis. PMID- 25130275 TI - Continuous eclogite melting and variable refertilisation in upwelling heterogeneous mantle. AB - Large-scale tectonic processes introduce a range of crustal lithologies into the Earth's mantle. These lithologies have been implicated as sources of compositional heterogeneity in mantle-derived magmas. The model being explored here assumes the presence of widely dispersed fragments of residual eclogite (derived from recycled oceanic crust), stretched and stirred by convection in the mantle. Here we show with an experimental study that these residual eclogites continuously melt during upwelling of such heterogeneous mantle and we characterize the melting reactions and compositional changes in the residue minerals. The chemical exchange between these partial melts and more refractory peridotite leads to a variably metasomatised mantle. Re-melting of these metasomatised peridotite lithologies at given pressures and temperatures results in diverse melt compositions, which may contribute to the observed heterogeneity of oceanic basalt suites. We also show that heterogeneous upwelling mantle is subject to diverse local freezing, hybridization and carbonate-carbon-silicate redox reactions along a mantle adiabat. PMID- 25130274 TI - Microglial regulation of immunological and neuroprotective functions of astroglia. AB - Microglia and astroglia play critical roles in the development, function, and survival of neurons in the CNS. However, under inflammatory conditions the role of astrogliosis in the inflammatory process and its effects on neurons remains unclear. Here, we used several types of cell cultures treated with the bacterial inflammogen LPS to address these questions. We found that the presence of astroglia reduced inflammation-driven neurotoxicity, suggesting that astrogliosis is principally neuroprotective. Neutralization of supernatant glial cell line derived neurotrophic factor (GDNF) released from astroglia significantly reduced this neuroprotective effect during inflammation. To determine the immunological role of astroglia, we optimized a highly-enriched astroglial culture protocol and demonstrated that LPS failed to induce the synthesis and release of TNF-alpha and iNOS/NO. Instead we found significant enhancement of TNF-alpha and iNOS expression in highly-enriched astroglial cultures required the presence of 0.5-1% microglia, respectively. Thus suggesting that microglial-astroglial interactions are required for LPS to induce the expression of pro-inflammatory factors and GDNF from astroglia. Specifically, we found that microglia-derived TNF-alpha plays a pivotal role as a paracrine signal to regulate the neuroprotective functions of astrogliosis. Taken together, these findings suggest that astroglia may not possess the ability to directly recognize the innate immune stimuli LPS, but rather depend on crosstalk with microglia to elicit release of neurotrophic factors as a counterbalance to support neuronal survival from the collateral damage generated by activated microglia during neuroinflammation. PMID- 25130276 TI - Prenatal testosterone of progenitors could be involved in the etiology of both anorexia nervosa and autism spectrum disorders of their offspring. AB - OBJECTIVES: High intrauterine testosterone (T) levels seem to play a role in the development of autism spectrum disorders (ASDs), but their role in anorexia nervosa (AN) is controversial. Parents with masculinized 2D:4D ratios, a marker of the organizational effects of T, may have other relevant biological characteristics, in particular exposing their offspring to high T levels in the prenatal environment. This would increase the likelihood of their offspring developing these disorders. METHODS: The present study examined whether parents of offspring with AN (n=34; mean age= 51) and ASD (n=36; mean age=45) differ from control parents (n=40; mean age=43) in 2D:4D ratio, as well as by salivary T levels and its relationships. RESULTS: Our results revealed that AN and ASD parents (fathers and mothers) have masculinized 2D:4D ratios of the right hand compared to control parents. However, the difference compared to controls was larger in the ASD than the AN group. Furthermore, current salivary T levels were negatively related to the 2D:4D ratio in ASD and AN parents only. CONCLUSIONS: Our data partially support the view of high prenatal masculinization as a potential intermediate phenotype to the development of these disorders in their offspring. PMID- 25130277 TI - Abiotic stress tolerance and competition-related traits underlie phylogenetic clustering in soil bacterial communities. AB - Soil bacteria typically coexist with close relatives generating widespread phylogenetic clustering. This has been ascribed to the abiotic filtering of organisms with shared ecological tolerances. Recent theoretical developments suggest that competition can also explain the phylogenetic similarity of coexisting organisms by excluding large low-competitive clades. We propose that combining the environmental patterns of traits associated with abiotic stress tolerances or competitive abilities with phylogeny and abundance data, can help discern between abiotic and biotic mechanisms underlying the coexistence of phylogenetically related bacteria. We applied this framework in a model system composed of interspersed habitats of highly contrasted productivity and comparatively dominated by biotic and abiotic processes, i.e. the plant patch-gap mosaic typical of drylands. We examined the distribution of 15 traits and 3290 bacterial taxa in 28 plots. Communities showed a marked functional response to the environment. Conserved traits related to environmental stress tolerance (e.g. desiccation, formation of resistant structures) were differentially selected in either habitat, while competition related traits (e.g. organic C consumption, formation of nutrient-scavenging structures) prevailed under high resource availability. Phylogenetic clustering was stronger in habitats dominated by biotic filtering, suggesting that competitive exclusion of large clades might underlie the ecological similarity of co-occurring soil bacteria. PMID- 25130278 TI - Association between binge eating and attention-deficit/hyperactivity disorder in two pediatric community mental health clinics. AB - OBJECTIVE: Attention-Deficit/ Hyperactivity Disorder (ADHD) has been linked with obesity; however its relationship with binge eating (BE) is less clear. We aimed to explore the associations among ADHD, weight, and BE in pediatric mental health clinics. METHOD: We retrospectively reviewed consecutive intakes in two pediatric mental health clinics (N = 252). BE was assessed using the C-BEDS scale. Associations between ADHD, BE, and BMI-z score were assessed via regression. RESULTS: Mean age was 10.8 (3.7 SD) years. Twelve percent (n = 31) had BE. The association between ADHD and BE was statistically significant (OR 16.1, p < .001), and persisted after adjusting for comorbid diagnoses, medications, demographic variables, and clinic. There was a statistically significant association between ADHD and BMI z-scores (beta = 0.54, p < .001). After adjusting for BE, the relationship between ADHD and BMI z-scores was attenuated (beta = 0.35, p = .025), and the coefficient for BE was decreased (beta = 0.75, p = .001). Although stimulant use was associated with a three-fold increase in odds of BE (OR 3.16, p = .006), stimulants were not associated with greater BMI-z scores (beta = 0.18, p = .32). DISCUSSION: There was a significant association between ADHD and BE in two pediatric mental health clinics. Although these data are cross-sectional, and cannot be used to make causal inferences, these findings are compatible with the hypothesis that BE partially mediates the association between ADHD and BMI z-scores. In mental health clinics, children with ADHD may present as overweight or obese. Further, children with ADHD may exhibit BE. Future prospective studies should elucidate the complex relationships among ADHD, weight, stimulants, and BE. PMID- 25130279 TI - Appropriateness of the definition of 'sedentary' in young children: Whole-room calorimetry study. AB - OBJECTIVES: The present study aimed to measure the energy cost of three common sedentary activities in young children to test whether energy expended was consistent with the recent consensus definition of 'sedentary' as 'any behaviour conducted in a sitting or reclining posture and with an energy cost <= 1.5 metabolic equivalents (METs)' (Sedentary Behaviour Research Network, 2012). DESIGN: Observational study. METHODS: Whole-room calorimetry measures of television viewing, sitting at a table drawing and reading, and sitting on the floor playing with toys were made in 40 young children (mean age 5.3 years, SD 1.0). RESULTS: The energy cost of each sedentary activity was consistent with the recent consensus definition of sedentary: 1.17 METs (95% CI 1.07-1.27) for TV viewing; 1.38 METs (95% CI 1.30-1.46) for sitting at a table; and 1.35 METs (95% CI 1.28-1.43) for floor-based play. CONCLUSIONS: Common sedentary activities in young children have energy costs which are consistent with the recent consensus definition of 'sedentary', and the present study is supportive of this definition. PMID- 25130280 TI - The relationship between clinically measured hip rotational motion and shoulder biomechanics during the pitching motion. AB - OBJECTIVES: To examine how clinically measured hip motion is related to shoulder biomechanics during the pitching motion. DESIGN: Cross-sectional. METHODS: Bilateral hip rotational range of motion was measured clinically among 34 collegiate baseball pitchers. External rotation torque and maximum horizontal adduction range of motion of the throwing shoulder were measured using a three dimensional, high speed video capture system. RESULTS: Separate standard multiple regression analyses showed that the total hip rotational range of motion of the lead leg had a significant relationship with shoulder external rotation torque during the throwing motion (r=0.56, P=0.003). Both lead leg hip external rotation range of motion (r=-0.39, P=0.02) and internal rotation range of motion (r=0.42, P=0.009) made significant contributions to this dependent variable. Lead leg external rotation range of motion also had a significant negative relationship with shoulder horizontal adduction range of motion (r=-0.36, P=0.04). The total rotational range of motion of the trail leg had a significant relationship with shoulder horizontal adduction range of motion (r=0.43, P=0.04). However, trail leg external rotation range of motion was the only significant contributor to this relationship (r=-0.35, P=0.04). No other significant relationships were noted (r<0.37, P>0.11). CONCLUSIONS: Our results demonstrate that altered hip rotational range of motion, measured clinically, has a direct effect on the amount of external rotation torque and horizontal adduction range of motion of the shoulder during the throwing motion. PMID- 25130282 TI - The effects of serotonin1A receptor on female mice body weight and food intake are associated with the differential expression of hypothalamic neuropeptides and the GABAA receptor. AB - Both common eating disorders anorexia nervosa and bulimia nervosa are characteristically diseases of women. To characterize the role of the 5-HT1A receptor (5-HT1A-R) in these eating disorders in females, we investigated the effect of saline or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) treatment on feeding behavior and body weight in adult WT female mice and in adult 5-HT1A-R knockout (KO) female mice. Our results showed that KO female mice have lower food intake and body weight than WT female mice. Administration of 8-OH-DPAT decreased food intake but not body weight in WT female mice. Furthermore, qRT-PCR was employed to analyze the expression levels of neuropeptides, gamma-aminobutyric acid A receptor subunit beta (GABAA beta subunits) and glutamic acid decarboxylase in the hypothalamic area. The results showed the difference in food intake between WT and KO mice was accompanied by differential expression of POMC, CART and GABAA beta2, and the difference in body weight between WT and KO mice was associated with significantly different expression levels of CART and GABAA beta2. As such, our data provide new insight into the role of 5-HT1A-R in both feeding behavior and the associated expression of neuropeptides and the GABAA receptor. PMID- 25130283 TI - Phenylboronate chromatography selectively separates glycoproteins through the manipulation of electrostatic, charge transfer, and cis-diol interactions. AB - Phenylboronate chromatography (PBC) has been applied for several years, however details regarding the mechanisms of interactions between the ligand and biomolecules are still scarce. The goal of this work is to investigate the various chemical interactions between proteins and their ligands, using a protein library containing both glycosylated and nonglycosylated proteins. Differences in the adsorption of these proteins over a pH range from 4 to 9 were related to two main properties: charge and presence of glycans. Acidic or neutral proteins were strongly adsorbed below pH 8 although the uncharged trigonal form of phenylboronate (PB) is less susceptible to forming electrostatic and cis-diol interactions with proteins. The glycosylated proteins were only adsorbed above pH 8 when the electrostatic repulsion between the boronate anion and the protein surface was mitigated (at 200 mM NaCl). All basic proteins were highly adsorbed above pH 8 with PB also acting as a cation-exchanger with binding occurring through electrostatic interactions. Batch adsorption performed at acidic conditions in the presence of Lewis base showed that charge-transfer interactions are critical for protein retention. This study demonstrates the multimodal interaction of PBC, which can be a selective tool for separation of different classes of proteins. PMID- 25130284 TI - Authors' response to letter by Ritzen et al. (Published online 25 July 2014, DOI: 10.1111/cen.12531). PMID- 25130281 TI - Results of a randomized, double-blind, parallel-group, placebo- and active controlled, multicenter study of mirabegron, a beta3-adrenoceptor agonist, in patients with overactive bladder in Asia. AB - AIMS: To assess the efficacy and safety of mirabegron 50 mg once daily compared with placebo and the active control, tolterodine extended-release (ER) 4 mg once daily, in patients with symptoms of overactive bladder (OAB) in Taiwan, Korea, China, and India. METHODS: A 12-week multinational, randomized, double-blind, parallel-group placebo- and active-controlled trial. The primary efficacy endpoint was change from baseline to final visit in mean number of micturitions/24 hr. Secondary endpoints were: mean number of urgency episodes, incontinence episodes and urge incontinence episodes/24 hr, mean number of nocturia episodes per night, mean volume voided per micturition, and quality-of life (QoL) scores as assessed by the King's Health Questionnaire (KHQ). RESULTS: Of 1,126 patients who were randomized to receive double-blind study drug, 921 patients (300, 311, and 310 in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively) completed the treatment period. Demographic characteristics were similar across treatment groups. A statistically significant improvement versus placebo in mean number of micturitions/24 hr was seen with mirabegron 50 mg at all timepoints (P < 0.05) as well as final visit (-0.57 with 95% confidence intervals [CIs] of [-1.04, -0.09], P = 0.019). There was no significant difference between treatment groups in improvement from baseline to final visit in any of the secondary outcome measures except volume voided per micturition. The overall incidence of drug-related adverse events was 17.2%, 15.8%, and 21.3%, in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively. CONCLUSIONS: Mirabegron 50 mg once daily for 12 weeks was superior to placebo in reducing the frequency of micturitions in patients with symptoms of OAB in Taiwan, Korea, China, and India. PMID- 25130285 TI - Inability of Turbidimetry Method in Detecting Glycated Hemoglobin to Select Diabetes Mellitus Patients According to Their Concentrations of Blood Glucose Levels. AB - BACKGROUND: Diabetes mellitus is a chronicle illness in which there is a high blood glucose level defined as hyperglycemia, resulted by a deficiency in insulin secretion and/or in its action. Nowadays, it is being seen as a public health problem and is reaching increasing proportions with regard to the appearance of new cases. For diagnosis, sensible and accurate methods should be used to avoid complications of the sickness. The measure of glycated hemoglobin may not be used for diagnosis, but is the reference method to evaluate the grade of glycemic control in the long term, reflecting the blood glucose level in the latest 2-3 months. The aim of this study was to evaluate the grade of concordance between turbidimetry and liquid chromatography methods in the glycated hemoglobin determination and to estimate the sensibility and specificity values of turbidimetry. METHODS: This study included 133 blood samples obtained from patients and healthy donors, ageing between 18 and 80 years with glycemic values between 58 and 473 mg/dl. RESULTS AND CONCLUSION: Turbidimetry is a useful method for determining glycemic levels above 100 and over 200 mg/dl, but does not have the ability to select samples with intermediary blood glucose concentrations. PMID- 25130286 TI - Ontogenetic cell death and phagocytosis in the visual system of vertebrates. AB - Programmed cell death (PCD), together with cell proliferation, cell migration, and cell differentiation, is an essential process during development of the vertebrate nervous system. The visual system has been an excellent model on which to investigate the mechanisms involved in ontogenetic cell death. Several phases of PCD have been reported to occur during visual system ontogeny. During these phases, comparative analyses demonstrate that dying cells show similar but not identical spatiotemporally restricted patterns in different vertebrates. Additionally, the chronotopographical coincidence of PCD with the entry of specialized phagocytes in some regions of the developing vertebrate visual system suggests that factors released from degenerating cells are involved in the cell migration of macrophages and microglial cells. Contradicting this hypothesis however, in many cases the cell corpses generated during degeneration are rapidly phagocytosed by neighboring cells, such as neuroepithelial cells or Muller cells. In this review, we describe the occurrence and the sites of PCD during the morphogenesis and differentiation of the retina and optic pathways of different vertebrates, and discuss the possible relationship between PCD and phagocytes during ontogeny. PMID- 25130288 TI - Morphological properties of the last primaries, the tail feathers, and the alulae of Accipiter nisus, Columba livia, Falco peregrinus, and Falco tinnunculus. AB - We investigated the mechanical properties (Young's modulus, bending stiffness, barb separation forces) of the tenth primary of the wings, of the alulae and of the middle tail feathers of Falco peregrinus. For comparison, we also investigated the corresponding feathers in pigeons (Columba livia), kestrels (Falco tinnunculus), and sparrowhawks (Accipiter nisus). In all four species, the Young's moduli of the feathers ranged from 5.9 to 8.4 GPa. The feather shafts of F. peregrinus had the largest cross-sections and the highest specific bending stiffness. When normalized with respect to body mass, the specific bending stiffness of primary number 10 was highest in F. tinnunculus, while that of the alula was highest in A. nisus. In comparison, the specific bending stiffness, measured at the base of the tail feathers and in dorso-ventral bending direction, was much higher in F. peregrinus than in the other three species. This seems to correlate with the flight styles of the birds: F. tinnunculus hovers and its primaries might therefore withstand large mechanical forces. A. nisus has often to change its flight directions during hunting and perhaps needs its alulae for this maneuvers, and in F. peregrinus, the base of the tail feathers might need a high stiffness during breaking after diving. PMID- 25130287 TI - Diagnosing and following adult patients with acute myeloid leukaemia in the genomic age. AB - The diagnosis and follow-up process of adult patients with acute myeloid leukaemia (AML) is challenging to clinicians and laboratory staff alike. While several sets of recommendations have been published over the years, the development of high throughput screening and characterization for both genetic and epigenetic events have evolved with astonishing speed. Here we attempt to provide a practical guide to diagnose and follow adult AML patients with a focus on how to balance the wealth of information on the one hand, with the restriction put on these processes in terms of time, feasibility and economy when caring for these patients, on the other. PMID- 25130289 TI - A randomized trial of cefozopran versus cefepime as empirical antibiotic treatment of febrile neutropenia in pediatric cancer patients. AB - BACKGROUND: Febrile neutropenia (FN) is a common and serious complication of cancer chemotherapy associated with significant morbidity and mortality. Cefozopran (CZOP) is a potential candidate for empirical monotherapy in FN. However, studies on the use of CZOP as empirical treatment for pediatric patients with FN are quite limited. The purpose of this study was to compare the efficacy and safety of CZOP with cefepime (CFPM) empirical monotherapy in pediatric cancer patients with FN. PROCEDURES: A total of 64 patients with 224 episodes of FN were randomly assigned to receive antibiotic therapy with either CZOP (100 mg/kg/day) or CFPM (100 mg/kg/day). Of these episodes, 223 were considered eligible for the study. Success was defined as resolution of febrile episodes and clinical signs of infection within 120 hr following the start of antibiotic therapy. RESULTS: The success rate was not significantly different between the CZOP (64.0%) and CFPM (56.3%) groups (P = 0.275). Duration of fever, duration of antibiotic therapy, and the success rate in patients with blood stream infection did not differ between the two groups. There was no infection-related mortality in the study period. CONCLUSION: Both CZOP and CFPM as monotherapy appear to be effective and safe in pediatric patients. This study suggests that CZOP has satisfactory efficacy and is well tolerated as initial empirical therapy for pediatric cancer patients with FN. PMID- 25130290 TI - Screening for obstructive sleep apnea in children with syndromic cleft lip and/or palate. AB - BACKGROUND: Craniofacial malformations including cleft lip and/or palate (CL/P) increase risk for obstructive sleep apnea (OSA). While 30% of CL/P occurs in the context of underlying genetic syndromes, few studies have investigated the prevalence of OSA in this high-risk group. This study aims to determine the incidence and risk factors of positive screening for OSA in this complex patient population. METHODS: The Pediatric Sleep Questionnaire (PSQ) was prospectively administered to all patients cared for by the cleft lip and palate clinic at the Children's Hospital of Philadelphia between January 2011 and August 2013. The PSQ is a 22-item, validated screening tool for OSA with a sensitivity and specificity of 0.83 and 0.87 in detecting an apnea-hypopnea index (AHI) >5/hour in healthy children. The Fisher exact and Chi-square tests were used for purposes of comparison. RESULTS: 178 patients with syndromic CL/P completed the PSQ. Mean cohort age was 8.1 +/- 4.4 years. Patients were predominately female (53.9%), Caucasian (78.1%), and had Veau Class II cleft (50.6%). Craniofacial syndromes included isolated Pierre Robin Sequence (PRS) (29.8%), 22q11.2 deletion syndrome (14.6%), Van der Woude syndrome (6.7%), and other rare genetic abnormalities (28.8%). The overall incidence of positive OSA screening was 32.0%. Males were at increased risk for positive OSA screening (P = 0.030), as were non-Caucasians (P = 0.044). Symptoms with the highest positive predictive value for OSA were "others comment on child appearing sleepy" (76.2%) and "stops breathing during the night" (75.0%). Notably, patients with 22q11.2 deletion syndrome were at highest risk for positive screens (50.0%, P = 0.042). CONCLUSIONS: Nearly a third of our patients with syndromic CL/P screened positively for OSA (32.0%), highlighting the importance of screening in this at-risk population. Future work will correlate screening results with polysomnograms to help validate these findings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, III. PMID- 25130291 TI - Customized negative pressure wound therapy for intractable auricular defects using alginate dressings and feeding tubes. PMID- 25130292 TI - Variations in 30-day hospital readmission rates across primary care clinics within a tertiary referral center. AB - BACKGROUND: Reducing hospital readmissions is a national healthcare priority. Little is known about how readmission rates vary across unique primary care practices. OBJECTIVE: To calculate all-cause 30-day hospital readmission rates at the level of individual primary care practices and identify factors associated with variations in these rates. DESIGN: Retrospective analysis SETTING: Seven primary care clinics affiliated with the University of California, San Francisco (UCSF). PATIENTS: Adults >=18 years old with a primary care provider (PCP) at UCSF MEASUREMENTS: All-cause 30-day readmission rates were calculated for primary care clinics for discharges between July 1, 2009 and June 30, 2012. We built a model to identify demographic, clinical, and hospital factors associated with variation in rates. RESULTS: There were 12,564 discharges for patients belonging to the 7 clinics, with 8685 index discharges and 1032 readmissions. Readmission rates varied across practices, from 14.9% in Human Immunodeficiency Virus primary care and 7.7% in women's health. In multivariable analyses, factors associated with variation in readmission rates included: male gender (odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.05-1.40), Medicare insurance (OR: 1.31, 95% CI: 1.05, 1.64; Ref = private), Medicare-Medicaid dual eligible (OR: 1.26, 95% CI: 1.01-1.56), multiple comorbidities, and admitting services. Patients with a departed PCP awaiting transfer assignment to a new PCP had an OR of 1.59 (95% CI: 1.16-2.17) compared with having a current faculty PCP. CONCLUSIONS: Primary care practices are important partners in improving care transitions and reducing hospital readmissions, and this study introduces a new way to view readmission rates. PCP turnover may be an important risk factor for hospital readmissions. PMID- 25130293 TI - Long-term efficacy, safety, and side effect profile of botulinum toxin in dystonia: a 20-year follow-up. AB - Most long-term studies of the efficacy and safety profile of botulinum toxin (BoNT) in the treatment of dystonia are limited by lack of objective assessments, relatively small sample size, or short follow-up periods. We present one of the longest follow-up studies of BoNT treatment. This is a retrospective, longitudinal study that analyzes data on 89 patients treated with BoNT for dystonia at our Movement Disorders Clinic for up to 26 years (mean follow-up period of 18.5 years). The mean ages at the time of the first and last injections were 49 and 68 years old, respectively. The most common diagnoses were cervical dystonia (N = 51), blepharospasm (N = 34), and oromandibular dystonia (N = 26). The total number of onabotulinumtoxinA units received during the first injection was 140.3 as compared to 224.5 at the last injection (p < 0.0001). The global response effect was 3.18 after the first injection session and 3.57 after the last injection (p < 0.0001). The duration of response after the initial injection session and at the last injection was 16.33 weeks versus 19.42 weeks (p 0.0037), respectively. Adverse events, typically related to injection site, were reported in 19% of the visits. This series of dystonia patients with the longest reported treatment with BoNT provide evidence that in selected patients repeated chemodenervation is associated with sustained symptomatic benefit, decreased latency effect, and prolonged duration of therapeutic response. Despite the higher requirement of mean units per visit over time, only 19% of all treatment cycles are associated with adverse, but tolerable, side effects. PMID- 25130294 TI - Qualitative and spatial metabolite profiling of lichens by a LC-MS approach combined with optimised extraction. AB - INTRODUCTION: Lichens are self-sustaining partnerships comprising fungi as shape forming partners for their enclosed symbiotic algae. They produce a tremendous diversity of metabolites (1050 metabolites described so far). OBJECTIVES: A comparison of metabolic profiles in nine lichen species belonging to three genera (Lichina, Collema and Roccella) by using an optimised extraction protocol, determination of the fragmentation pathway and the in situ localisation for major compounds in Roccella species. METHODS: Chemical analysis was performed using a complementary study combining a Taguchi experimental design with qualitative analysis by high-performance liquid chromatography coupled with mass spectrometry techniques. RESULTS: Optimal conditions to obtain the best total extraction yield were determined as follows: mortar grinding to a fine powder, two successive extractions, solid:liquid ratio (2:60) and 700 rpm stirring. Qualitative analysis of the metabolite profiling of these nine species extracted with the optimised method was corroborated using MS and MS/MS approaches. Nine main compounds were identified: 1 beta-orcinol, 2 orsellinic acid, 3 putative choline sulphate, 4 roccellic acid, 5 montagnetol, 6 lecanoric acid, 7 erythrin, 8 lepraric acid and 9 acetylportentol, and several other compounds were reported. Identification was performed using the m/z ratio, fragmentation pathway and/or after isolation by NMR analysis. The variation of the metabolite profile in differently organised parts of two Roccella species suggests a specific role of major compounds in developmental stages of this symbiotic association. CONCLUSION: Metabolic profiles represent specific chemical species and depend on the extraction conditions, the kind of the photobiont partner and the in situ localisation of major compounds. PMID- 25130295 TI - IL-12-and IL-23 in health and disease. AB - Interleukin (IL)-12 and IL-23 play important roles in the development of experimental autoimmune disease models and numerous afflictions affecting humans. Preclinical data over the last 20 years combined with successful clinical trials has identified a clear relationship between IL-12, IL-23 and the generation of pathogenic T helper cells capable of orchestrating tissue inflammation. Observations made in the clinic have shown that IL-12p40, a common subunit shared by IL-12 and IL-23, is critical to pathologies associated with psoriasis, inflammatory bowel disease (IBD) and tumor growth. These advancements have set in motion the development of a number of potential therapeutics aimed at manipulating IL-12/23 signaling pathways in both mice and humans. This review will discuss a brief history of the understanding and expansion of the IL-12 cytokine family, some difficulties associated with preclinical data interpretation and finally the medicinal interventions that have been developed to combat IL-12/23-driven autoimmune disorders. PMID- 25130296 TI - Exploiting differential expression of the IL-7 receptor on memory T cells to modulate immune responses. AB - Interleukin-7 is a non-redundant growth, differentiation and survival factor for human T lymphocytes. Most circulating, mature T cells express the receptor for IL 7, but not all. Importantly, CD4 Tregs express greatly reduced levels of IL-7R compared to conventional CD4 T cells, presenting an opportunity to selectively target the latter cells with either more IL-7 to boost responses, or to block IL 7 signalling to limit responses. This article reviews what is known about regulation of IL-7R expression, and recent progress in therapeutic approaches related to IL-7 and its receptor. PMID- 25130298 TI - AFM images of the dark biocidal action of cationic conjugated polyelectrolytes and oligomers on Escherichia coli. AB - Polymers and oligomers with conjugated phenylene ethynylene or thiophene ethynylene backbones have been shown to be potent antimicrobials. The mechanisms by which they act have been unclear, though AFM imaging of Escherichia coli cells before and after exposure to two such biocides, PPE-Th polymer and EO-OPE-1(C3), shows their effects on cell surface structure. Dried, unexposed E. coli cells could be imaged at resolution high enough to discern the physical structure of the cell surfaces, including individual porin proteins and their distribution on the cell. Exposure to 30 MUg/mL PPE-Th polymer caused major cell surface disruption due to either emulsification of the outer membrane or the formation of polymer aggregates or both. In contrast, exposure to 30 MUg/mL EO-OPE-1(C3) oligomer did not cause large-scale membrane disruption but did cause apparent reorganization of the surface proteins into linear arrays or protein-lipid-OPE complexes that dominate on a small scale. E. coli cells were also successfully imaged underwater, allowing a real-time AFM image series as cells were exposed to 30 MUg/mL EO-OPE-1(C3). Solution exposure caused the cell surfaces to noticeably increase their roughness over time. These results agree with proposed mechanisms for cell killing by PPE-Th and EO-OPE-1(C3) put forth by Wang et al.1 in which PPE-Th kills by large-scale disruption of the outer membrane and EO-OPE-1(C3) kills by membrane reorganization with possible pore formation. PMID- 25130297 TI - A randomized controlled clinical trial of levofloxacin 750 mg versus 500 mg intravenous infusion in the treatment of community-acquired pneumonia. AB - The objective of this study was to compare the efficacy and safety of levofloxacin 750 mg for 5 days versus 500 mg for 7-14 days intravenous (IV) in the treatment of community-acquired pneumonia (CAP). This clinical trial was the first of its kind conducted in Chinese people and also in Asian population. A total of 241 were enrolled and randomized to 750 mg group (n = 121) or 500 mg (n = 120) group from 10 study centers. The median treatment duration was 5.0 days in 750 mg and 9.0 days in 500 mg group. The median total dose was 3750 mg in 750 mg and 4500 mg in 500 mg group. The bacterial eradication rate was 100% in both groups. The overall efficacy rate in 750 mg group was 86.2% (94/109), and 84.7% (94/111), in 500 mg group of full analysis set visit 4, 95% confidence interval of 1.6% (-7.8-10.9%); the statistical results showed that 750 mg group was non inferior to 500 mg group. The most common clinical adverse drug reactions were injection site adverse reactions in both 750 mg group and 500 mg group; the other common adverse drug reactions were insomnia, nausea, skin rash, etc. The most common drug-related laboratory abnormalities were neutrophil percentage decreased, decreased white blood cell count, alanine aminotransferase, and aspartate aminotransferase elevation in both 750 mg group and 500 mg group. Most of adverse drug reactions were mild in severity and well-tolerated. In summary, the regimen of levofloxacin 750 mg IV for 5 days was at least as effective and well tolerated as 500 mg IV for 7-14 days for the treatment of CAP. PMID- 25130299 TI - Rats' choices with token stimuli in concurrent variable-interval schedules. AB - Four rats responded on concurrent variable-interval schedules that delivered token stimuli (stimulus lights arranged vertically above each of two side levers). During exchange periods, each token could be exchanged for one food pellet by responding on a center lever, with one response required for each pellet delivery. In different conditions, the exchange requirements (number of tokens that had to be earned before they could be exchanged for food) varied between one and four for the two response levers. The experiments were closely patterned after research with pigeons by Mazur and Biondi (2013), and the results from the rats in the present experiment were similar. Response percentages on the two levers changed as each additional token was earned, and these patterns indicated that choice was controlled by both the time to the exchange periods and the number of food pellets that were delivered in the exchange period. In some conditions, the exchange requirement was three tokens for each lever, but the token lights were not turned on as they were earned for one of the two keys. The rats showed a slight preference for the lever without the token lights, which may indicate that the token lights were not serving as conditioned reinforcers (a result also found by Mazur and Biondi with pigeons). Overall, these results suggest that, in this choice procedure, the token stimuli served primarily as discriminative stimuli that signaled the temporal proximity and quantity of the primary reinforcer, food. PMID- 25130300 TI - The association between secondhand smoke and sleep-disordered breathing in children: a systematic review. AB - OBJECTIVE: To systematically review existing literature on the association between secondhand smoke and sleep-disordered breathing in children. DATA SOURCES: PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus. REVIEW METHODS: Inclusion criteria included English-language papers containing original human data, with seven or more subjects and age <18 years. Data were systematically collected on study design, patient demographics, clinical characteristics/outcomes, and level of evidence. Two investigators independently reviewed all manuscripts. RESULTS: The initial search yielded 72 abstracts; 18 articles were ultimately included with a total study population of 47,462 patients. Fifteen (83%) articles found a statistically significant association between secondhand smoke and sleep-disordered breathing. All were case-control studies. Quality of articles based on the Newcastle-Ottawa scale averaged 5.8/9 stars. Secondhand smoke was characterized by serum cotinine testing in only two (11%) studies. Sleep-disordered breathing was quantified by polysomnography in only four (22%) of the studies and only one (6%) classified subject using polysomnography exclusively. Habitual snoring was the most common form of sleep disordered breathing studied in 14/18 (78%) studies, whereas obstructive sleep apnea was reported in one (6%) study and sleep-related hypoxia in another (6%) study. CONCLUSIONS: Although the majority of studies included in this review found a significant association between secondhand smoke and sleep-disordered breathing, all of them were evidence level 3b, for an overall grade of B (Oxford Centre for Evidence-based Medicine). Further higher-quality studies should be performed in the future to better evaluate the relationship between second- smoke and sleep-disordered breathing in children. PMID- 25130302 TI - Identification of a developmentally-regulated and psychostimulant-inducible novel rat gene mrt3 in the neocortex. AB - The psychotomimetic effects of stimulant drugs including amphetamines and cocaine are known to change during the postnatal development in humans and experimental animals. To obtain an insight into the molecular basis of the onset of stimulant induced psychosis, we have explored the gene transcripts that differentially respond to methamphetamine (MAP) in the developing rat brains using a differential cloning technique, the RNA arbitrarily-primed PCR. We identified from the rat neocortex a novel and developmentally regulated MAP-inducible gene mrt3 (MAP responsive transcript 3) that is transcribed to a presumable non-coding RNA of 3.8kb and is located on the reverse strand of the F-box/LRR-repeat protein 17-like gene mapped on the rat chromosome Xq12. The mrt3 mRNAs are predominantly expressed in the brain and lung. Acute MAP injection upregulated the mrt3 expression in the neocortex at postnatal day 50, but not days 8, 15 and 23, in a D1 receptor antagonist-sensitive manner. This upregulation was mimicked by another stimulant, cocaine, whereas pentobarbital and D1 antagonist failed to alter the mrt3 expression. Moreover, repeated treatment with MAP for 5 days inhibited the ability of the challenge dose of MAP or cocaine to increase the neocortical mrt3 expression without affecting the basal mrt3 mRNA levels on day 14 of withdrawal. These late-developing, cocaine-cross reactive, D1 antagonist sensitive and long-term regulations of mrt3 by MAP are similar to those of stimulant-induced behavioral sensitization, a model of the onset and relapse of stimulant-induced psychosis and schizophrenia, and therefore may be associated with the pathophysiology of the model. PMID- 25130303 TI - N-acetyl-aspartate (NAA) as a correlate of pharmacological treatment in psychiatric disorders: a systematic review. AB - The amino-acid N-acetyl-aspartate (NAA) is located in neurons and the concentration of NAA correlates with neuronal mitochondrial function. The signal of NAA, as measured with proton magnetic resonance spectroscopy (1H-MRS), is considered to reflect both, neuronal density and integrity of neuronal mitochondria. A reduction of the NAA concentrations has been found in several psychiatric disorders. Newer studies report reversal of decreased NAA concentration with treatment. The objective of this review is to summarize the literature on NAA changes in association with psychopharmacological treatment in psychiatric disorders (affective disorders, obsessive-compulsive disorder, schizophrenia and dementia). The majority of studies identified increased NAA concentrations in response to treatment, while a smaller number of studies did not find this effect. The NAA increase seems to be neither specific for a certain disorder nor for a specific intervention. This suggests that the reduction of NAA may represent an altered functional (metabolic) state of neurons common to different psychiatric disorders and the increase after treatment to indicate functional restoration as one general effect of interventions. PMID- 25130301 TI - Transcranial electrical brain stimulation modulates neuronal tuning curves in perception of numerosity and duration. AB - Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method with many putative applications and reported to effectively modulate behaviour. However, its effects have yet to be considered at a computational level. To address this we modelled the tuning curves underlying the behavioural effects of stimulation in a perceptual task. Participants judged which of the two serially presented images contained more items (numerosity judgement task) or was presented longer (duration judgement task). During presentation of the second image their posterior parietal cortices (PPCs) were stimulated bilaterally with opposite polarities for 1.6s. We also examined the impact of three stimulation conditions on behaviour: anodal right-PPC and cathodal left-PPC (rA-lC), reverse order (lA-rC) and no-stimulation condition. Behavioural results showed that participants were more accurate in numerosity and duration judgement tasks when they were stimulated with lA-rC and rA-lC stimulation conditions respectively. Simultaneously, a decrease in performance on numerosity and duration judgement tasks was observed when the stimulation condition favoured the other task. Thus, our results revealed a double dissociation of laterality and task. Importantly, we were able to model the effects of stimulation on behaviour. Our computational modelling showed that participants' superior performance was attributable to a narrower tuning curve- smaller standard deviation of detection noise. We believe that this approach may prove useful in understanding the impact of brain stimulation on other cognitive domains. PMID- 25130304 TI - SDF-1/CXCR4 axis in Tie2-lineage cells including endothelial progenitor cells contributes to bone fracture healing. AB - CXC chemokine receptor 4 (CXCR4) is a specific receptor for stromal-derived factor 1 (SDF-1). SDF-1/CXCR4 interaction is reported to play an important role in vascular development. On the other hand, the therapeutic potential of endothelial progenitor cells (EPCs) in fracture healing has been demonstrated with mechanistic insight of vasculogenesis/angiogenesis and osteogenesis enhancement at sites of fracture. The purpose of this study was to investigate the influence of the SDF-1/CXCR4 pathway in Tie2-lineage cells (including EPCs) in bone formation. We created CXCR4 gene conditional knockout mice using the Cre/loxP system and set two groups of mice: Tie2-Cre(ER) CXCR4 knockout mice (CXCR4(-/-) ) and wild-type mice (WT). We report here that in vitro, EPCs derived from of CXCR4(-/-) mouse bone marrow demonstrated severe reduction of migration activity and EPC colony-forming activity when compared with those derived from WT mouse bone marrow. In vivo, radiological and morphological examinations showed fracture healing delayed in the CXCR4(-/-) group and the relative callus area at weeks 2 and 3 was significantly smaller in CXCR4(-/-) group mice. Quantitative analysis of capillary density at perifracture sites also showed a significant decrease in the CXCR4(-/-) group. Especially, CXCR4(-/-) group mice demonstrated significant early reduction of blood flow recovery at fracture sites compared with the WT group in laser Doppler perfusion imaging analysis. Real-time RT-PCR analysis showed that the gene expressions of angiogenic markers (CD31, VE cadherin, vascular endothelial growth factor [VEGF]) and osteogenic markers (osteocalcin, collagen 1A1, bone morphogenetic protein 2 [BMP2]) were lower in the CXCR4(-/-) group. In the gain-of-function study, the fracture in the SDF-1 intraperitoneally injected WT group healed significantly faster with enough callus formation compared with the SDF-1 injected CXCR4(-/-) group. We demonstrated that an EPC SDF-1/CXCR4 axis plays an important role in bone fracture healing using Tie2-Cre(ER) CXCR4 conditional knockout mice. PMID- 25130305 TI - What is a paternal effect? AB - Maternal effects are now universally recognised as a form of nongenetic parental influence on offspring but, until recently, paternal effects were regarded as an anomaly. Although it is now clear that paternal effects are both widespread and important, their proximate basis and evolutionary consequences have received little attention and remain poorly understood. In particular, because many paternal effects are mediated by maternal responses such as differential allocation, the boundary between paternal and maternal effects is sometimes blurred. We distinguish here three basic types of paternal effect and clarify the role of maternal responses in these effects. We also outline key questions that can serve as a road map for research on the proximate basis and evolutionary implications of paternal effects. PMID- 25130306 TI - Failure mode analysis in adrenal vein sampling: a single-center experience. AB - PURPOSE: To analyze failure modes in a high-volume adrenal vein sampling (AVS) practice in an effort to identify preventable causes of nondiagnostic sampling. MATERIALS AND METHODS: A retrospective database was constructed containing 343 AVS procedures performed over a 10-year period. Each nondiagnostic AVS procedure was reviewed for failure mode and correlated with results of any repeat AVS. Data collected included selectivity index, lateralization index, adrenalectomy outcomes if performed, and details of AVS procedure. All AVS procedures were performed after cosyntropin stimulation, using sequential technique. RESULTS: AVS was nondiagnostic in 12 of 343 (3.5%) primary procedures and 2 secondary procedures. Failure was right-sided in 8 (57%) procedures, left-sided in 4 (29%) procedures, bilateral in 1 procedure, and neither in 1 procedure (laboratory error). Failure modes included diluted sample from correctly identified vein (n = 7 [50%]; 3 right and 4 left), vessel misidentified as adrenal vein (n = 3 [21%]; all right), failure to locate an adrenal vein (n = 2 [14%]; both right), cosyntropin stimulation failure (n = 1 [7%]; diagnostic by nonstimulated criteria), and laboratory error (n = 1 [7%]; specimen loss). A second AVS procedure was diagnostic in three of five cases (60%), and a third AVS procedure was diagnostic in one of one case (100%). Among the eight patients in whom AVS ultimately was not diagnostic, four underwent adrenalectomy based on diluted AVS samples, and one underwent adrenalectomy based on imaging; all five experienced improvement in aldosteronism. CONCLUSIONS: A substantial percentage of AVS failures occur on the left, all related to dilution. Even when technically nondiagnostic per strict criteria, some "failed" AVS procedures may be sufficient to guide therapy. Repeat AVS has a good yield. PMID- 25130307 TI - Contemporary systematic review and meta-analysis of early outcomes with percutaneous treatment for infrapopliteal atherosclerotic disease. AB - PURPOSE: The need for specialty devices to improve the technical outcome of endovascular interventions is dependent on the rate of early failure in such procedures. This meta-analysis assessed procedural outcomes of such interventions to elucidate the rate of early procedural failures and the need for such specialty devices. MATERIALS AND METHODS: MEDLINE and EMBASE were searched for contemporary studies (2000-2012) reporting procedural or short-term outcomes for revascularization of infrapopliteal atherosclerotic lesions. A random-effects metaanalysis was performed, which included post hoc comparisons among treatment groups. RESULTS: A total of 42 studies with 52 treatment arms representing 3,660 unique patients were included. Technical success rates were higher with bare metal stents (BMSs; 98.6%) than with atherectomy (92.2%; P < .05) or percutaneous transluminal angioplasty (PTA; 91.2%; P = .01), and higher with drug-eluting stents (DESs) than with PTA (P < .001). DES use had higher primary patency rates than atherectomy (P < .05), BMS use (P < .001), and PTA (P < .01). The 30-day rate of target lesion revascularization was significantly higher with PTA (8.1%) than with BMSs (2.2%; P < .05) and DESs (1.1%; P < .05). Thirty-day rates of major unplanned amputation (range, 1.5%-4.4%) and mortality (range, 0.9%-3.3%) were comparable among treatment groups. Significant heterogeneity among studies was noted for most PTA outcomes. Publication bias was evident for most PTA and DES outcomes. CONCLUSIONS: Early failure of percutaneous therapies in patients with infrapopliteal atherosclerotic lesions is device- and technique-dependent. Specialty devices designed to reduce technical failure rates may therefore be of benefit in this selected group of patients. Study results are confounded by inconsistent data reporting, heterogeneity of treatment effects, and publication bias. PMID- 25130308 TI - An economic analysis of sublobar resection versus thermal ablation for early stage non-small-cell lung cancer. AB - PURPOSE: To compare medical costs for a matched-pair cohort of Medicare patients with early-stage non-small-cell lung cancer (NSCLC) who underwent treatment with sublobar resection or thermal ablation. MATERIALS AND METHODS: Patients at least 65 years of age with stage IA/IB NSCLC treated with sublobar resection or thermal ablation from 2007 to 2009 were identified from Surveillance, Epidemiology, and End Results/Medicare-linked data and matched by propensity scores. The primary outcome of interest, cost from the payer's perspective, was derived from Medicare claims data. A partitioned inverse probability-weighted estimator was used to calculate mean and median treatment-related costs and costs at 1, 3, 12, 18, and 24 months after treatment. Baseline characteristics, Kaplan-Meier survival curves, and calculated cost variables were compared between the two groups. RESULTS: The final matched cohort of 128 patients had similar baseline characteristics and overall survival (P = .52). Patients who underwent ablation had significantly lower treatment-related costs than those who underwent sublobar resection (P < .001). The difference in median treatment-related cost was $16,105. At 1 month, 3 months, and 12 months after treatment, cumulative costs remained significantly different (P <= .011). Lower cost associated with ablations performed in the outpatient setting was a major contributor to the differences between the two treatment modalities, although inpatient ablations maintained a small cost advantage over sublobar resections. CONCLUSIONS: Among matched Medicare patients with stage I NSCLC, thermal ablation resulted in significantly lower treatment-related costs and cumulative medical costs 1 month, 3 months, and 12 months after treatment compared with sublobar resection. PMID- 25130309 TI - Reply: To PMID 24913549. PMID- 25130310 TI - Understanding the complex needs of automotive training at final assembly lines. AB - Automobile final assembly operators must be highly skilled to succeed in a low automation environment where multiple variants must be assembled in quick succession. This paper presents formal user studies conducted at OPEL and VOLVO Group to identify assembly training needs and a subset of requirements; and to explore potential features of a hypothetical game-based virtual training system. Stakeholder analysis, timeline analysis, link analysis, Hierarchical Task Analysis and thematic content analysis were used to analyse the results of interviews with various stakeholders (17 and 28 participants at OPEL and VOLVO, respectively). The results show that there is a strong case for the implementation of virtual training for assembly tasks. However, it was also revealed that stakeholders would prefer to use a virtual training to complement, rather than replace, training on pre-series vehicles. PMID- 25130311 TI - Assessment model for perceived visual complexity of automotive instrument cluster. AB - This research proposes an assessment model for quantifying the perceived visual complexity (PVC) of an in-vehicle instrument cluster. An initial study was conducted to investigate the possibility of evaluating the PVC of an in-vehicle instrument cluster by estimating and analyzing the complexity of its individual components. However, this approach was only partially successful, because it did not take into account the combination of the different components with random levels of complexity to form one visual display. Therefore, a second study was conducted focusing on the effect of combining the different components. The results from the overall research enabled us to suggest a basis for quantifying the PVC of an in-vehicle instrument cluster based both on the PVCs of its components and on the integration effect. PMID- 25130312 TI - Cisplatin-induced testicular toxicity in rats: the protective effect of arjunolic acid. AB - In the present study, the effect of arjunolic acid on testicular damage induced by intraperitoneal injection of rats with 7 mg/kg cisplatin was studied. Cisplatin induced a significant reduction in testicular weights, plasma testosterone, and testicular reduced glutathione levels in addition to a significant elevation of testicular malondialdehyde levels and testicular gene expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), and p38 mitogen-activated protein kinase (MAPK) when compared with the control group (p < 0.05). Lower tubular diameters and depletion of germ cells and irregular small seminiferous tubules with Sertoli cells only were observed in the cisplatin group. Arjunolic acid administration significantly corrected the changes in both biochemical and histopathological parameters. Arjunolic acid plays a significant protective role against cisplatin-induced testicular injury by attenuating oxidative stress parameters along with downregulation of iNOS, TNF-alpha, and p38-MAPK testicular expressions. PMID- 25130313 TI - Sensory modality-specific spatio-temporal dynamics in response to counting tasks. AB - From perception to behavior, the human brain processes information in a flexible and abstract manner independent of an input sensory modality. However, the mechanism of such multisensory neural information processing in the brain remains under debate. Relatedly, studies often aim to investigate whether certain brain regions behave in a modality-specific manner or invariantly. Previous studies regarding multisensory information processing have commonly reported only on the activation of brain regions in response to unimodal or multimodal sensory stimuli. However, less attention has been given to the modality effect on the dynamics of such regions, which could advance our understanding of neuronal information processing. In this study, we investigated whether brain regions show modality-specific or invariant high-temporal dynamics. Electrocardiogram (EEG) was recorded from healthy, normal subjects during beep-, flash- and click counting tasks, which corresponded to auditory, visual and tactile modalities, respectively. EEG dynamics regarding event-related spectral perturbations (ERSP) in ICA time-series data were compared across the sensory modalities using a multivariate pattern analysis. We found modality-specific EEG dynamics in the prefrontal cortex, whereas we found modality-specific and cross-modal dynamics in the early visual cortex. PMID- 25130314 TI - Nursing grand rounds: a strategy for promoting evidence-based learning among pediatric nurses. AB - This paper describes the collaboration of nurses from five specialty units within a large tertiary care pediatric hospital in the development and presentation of Nursing Grand Rounds (NGR). NGR was generated, prepared, and presented quarterly by bedside nurses to their peers in a professional format. NGR lasted 2hours, were simultaneously offered via Webinar, and incorporated literature reviews, guest/expert speakers, and case studies. In addition, attendees were eligible for continuing education credits (CEUs). Based on favorable evaluations, NGR is purported as a creative method for nurses to be kept up-to-date about evidence and knowledge unique to their patient population. PMID- 25130315 TI - Adipocyte transdifferentiation and its molecular targets. AB - According to the World Health Organization obesity is defined as the excessive accumulation of fat, which increases risk of other metabolic disorders such as insulin resistance, dyslipidemia, hypertension, cardiovascular diseases, etc. There are two types of adipose tissue, white and brown adipose tissue (BAT) and the latter has recently gathered interest of the scientific community. Discovery of BAT has opened avenues for a new therapeutic strategy for the treatment of obesity and related metabolic syndrome. BAT utilizes accumulated fatty acids for energy expenditure; hence it is seen as one of the possible alternates to the current treatment. Moreover, browning of white adipocyte on exposure to cold, as well as with some of the pharmacological agents presents exciting outcomes and indicates the feasibility of transdifferentiation. A better understanding of molecular pathways and differentiation factors, those that play a key role in transdifferentiation are of extreme importance in designing novel strategies for the treatment of obesity and associated metabolic disorders. PMID- 25130317 TI - Commentary on "biochemical and immunomorphological evaluation of hepatocyte growth factor and c-Met pathway in patients with critical limb ischemia": regenerative therapy of chronically ischaemic wounds: land in sight? PMID- 25130318 TI - Rafting through traffic: Membrane domains in cellular logistics. AB - The intricate and tightly regulated organization of eukaryotic cells into spatially and functionally distinct membrane-bound compartments is a defining feature of complex organisms. These compartments are defined by their lipid and protein compositions, with their limiting membrane as the functional interface to the rest of the cell. Thus, proper segregation of membrane proteins and lipids is necessary for the maintenance of organelle identity, and this segregation must be maintained despite extensive, rapid membrane exchange between compartments. Sorting processes of high efficiency and fidelity are required to avoid potentially deleterious mis-targeting and maintain cellular function. Although much molecular machinery associated with membrane traffic (i.e. membrane budding/fusion/fission) has been characterized both structurally and biochemically, the mechanistic details underlying the tightly regulated distribution of membranes between subcellular locations remain to be elucidated. This review presents evidence for the role of ordered lateral membrane domains known as lipid rafts in both biosynthetic sorting in the late secretory pathway, as well as endocytosis and recycling to/from the plasma membrane. Although such evidence is extensive and the involvement of membrane domains in sorting is definitive, specific mechanistic details for raft-dependent sorting processes remain elusive. PMID- 25130319 TI - Dual effect of thiol addition on fluorescent polymeric micelles: ON-to-OFF emissive switch and morphology transition. AB - The morphology transition from micelles to vesicles of a solution-state self assembled block copolymer, containing a fluorescent dye at the core-shell interface, has been induced by an addition-elimination reaction using a thiol, and has been shown to be coupled to a simultaneous ON-to-OFF switch in particle fluorescence. PMID- 25130316 TI - Effects of soluble extracts from Leishmania infantum promastigotes, Toxoplasma gondii tachyzoites on TGF-beta mediated pathways in activated CD4+ T lymphocytes. AB - Interference with transforming growth factor-beta-mediated pathways helps several parasites to survive for long periods in immunocompetent hosts. Macrophages and dendritic cells infected by Toxoplasma, Leishmania and Plasmodium spp. produce large amounts of transforming growth factor-beta and induce the differentiation of antigen-specific T-regulatory cells. Mechanisms not mediated by antigen presentation could also account for the expansion of T-regulatory cells in parasitic diseases and they also might be mediated through transforming growth factor-beta-receptor activated pathways. We explored the properties of soluble extracts from Leishmania infantum promastigotes, Toxoplasma gondii tachyzoites, Trichinella spiralis muscle larvae to expand the pool of T-regulatory cells in a population of polyclonally activated T cells in the absence of accessory cells, and compared their effects to those induced by Plasmodium falciparum extracts. Similarly to P. falciparum, L. infantum extracts activate the latent soluble form of transforming growth factor-beta and that bound to the membrane of activated T lymphocytes. The interaction of the active cytokine with transforming growth factor-beta receptor induces Foxp3 expression by activated lymphocytes, favoring their conversion through the T-regulatory phenotype. Both Toxoplasma gondii and L. infantum extracts are able to induce transforming growth factor-beta production by activated T cells in the absence of accessory cells. PMID- 25130320 TI - Survival of Atlantic salmon Salmo salar smolts through a hydropower complex. AB - This study evaluated Atlantic salmon Salmo salar smolt survival through the lower Penobscot River, Maine, U.S.A., and characterized relative differences in proportional use and survival through the main-stem of the river and an alternative migration route, the Stillwater Branch. The work was conducted prior to removal of two main-stem dams and operational changes in hydropower facilities in the Stillwater Branch. Survival and proportional use of migration routes in the lower Penobscot were estimated from multistate (MS) models based on 6 years of acoustic telemetry data from 1669 smolts and 2 years of radio-telemetry data from 190 fish. A small proportion (0.12, 95% c.i. = 0.06-0.25) of smolts used the Stillwater Branch, and mean survival through the two operational dams in this part of the river was relatively high (1.00 and 0.97). Survival at Milford Dam, the dam that will remain in the main-stem of the Penobscot River, was relatively low (0.91), whereas survival through two dams that were removed was relatively high (0.99 and 0.98). Smolt survival could decrease in the Stillwater Branch with the addition of two new powerhouses while continuing to meet fish passage standards. The effects of removing two dams in the main-stem are expected to be negligible for smolt survival based on high survival observed from 2005 to 2012 at those locations. Survival through Milford Dam was been well below current regulatory standards, and thus improvement of passage at this location offers the best opportunity for improving overall smolt survival in the lower river. PMID- 25130321 TI - Medical burden in bipolar disorder: findings from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE). AB - OBJECTIVES: Individuals with bipolar disorder have high rates of other medical comorbidity, which is associated with higher mortality rates and worse course of illness. The present study examined common predictors of medical comorbidity. METHODS: The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month, randomized comparative effectiveness trial. Baseline assessments included current and lifetime DSM-IV-TR diagnoses, demographic information, psychiatric and medical history, severity of psychiatric symptoms, level of functioning, and a fasting blood draw. Medical comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes, hyperlipidemia, and metabolic syndrome) and non-cardiovascular (e.g., seizures, asthma, and cancer). Additionally, we looked at comorbid substance use (e.g., smoking and drug dependence). RESULTS: We found that 96.3% of participants had at least one other medical comorbidity. Older age predicted a greater likelihood of having a cardiometabolic condition. Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition, but a greater chance of having other types of medical comorbidity. Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed, less time spent manic/hypomanic, and longer duration of illness. Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides. CONCLUSIONS: There appears to be a substantial medical burden associated with bipolar disorder, highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients. PMID- 25130322 TI - Shape-shift: semicircular canal morphology responds to selective breeding for increased locomotor activity. AB - Variation in semicircular canal morphology correlates with locomotor agility among species of mammals. An experimental evolutionary mouse model was used to test the hypotheses that semicircular canal morphology (1) evolves in response to selective breeding for increased locomotor activity, (2) exhibits phenotypic plasticity in response to early-onset chronic exercise, and (3) is unique in individuals possessing the minimuscle phenotype. We examined responses in canal morphology to prolonged wheel access and selection in laboratory mice from four replicate lines bred for high voluntary wheel-running (HR) and four nonselected control (C) lines. Linear measurements and a suite of 3D landmarks were obtained from 3D reconstructions of MUCT-scanned mouse crania (MUCT is microcomputed tomography). Body mass was smaller in HR than C mice and was a significant predictor of both radius of curvature and 3D canal shape. Controlling for body mass, radius of curvature did not differ statistically between HR and C mice, but semicircular canal shape did. Neither chronic wheel access nor minimuscle affected radius of curvature or canal shape These findings suggest that semicircular canal morphology is responsive to evolutionary changes in locomotor behavior, but the pattern of response is potentially different in small- versus large-bodied species. PMID- 25130323 TI - Barriers to evidence-based medicine: a systematic review. AB - INTRODUCTION: Evidence-based medicine (EBM) has emerged as an effective strategy to improve health care quality. The aim of this study was to systematically review and carry out an analysis on the barriers to EBM. METHODS: Different database searching methods and also manual search were employed in this study using the search words ('evidence-based' or 'evidence-based medicine' or 'evidence-based practice' or 'evidence-based guidelines' or 'research utilization') and (barrier* or challenge or hinder) in the following databases: PubMed, Scopus, Web of Knowledge, Cochrane library, Pro Quest, Magiran, SID. RESULTS: Out of 2592 articles, 106 articles were finally identified for study. Research barriers, lack of resources, lack of time, inadequate skills, and inadequate access, lack of knowledge and financial barriers were found to be the most common barriers to EBM. Examples of these barriers were found in primary care, hospital/specialist care, rehabilitation care, medical education, management and decision making. The most common barriers to research utilization were research barriers, cooperation barriers and changing barriers. Lack of resources was the most common barrier to implementation of guidelines. CONCLUSION: The result of this study shows that there are many barriers to the implementation and use of EBM. Identifying barriers is just the first step to removing barriers to the use of EBM. Extra resources will be needed if these barriers are to be tackled. PMID- 25130324 TI - A genome-wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus. AB - Heschl's gyrus (HG) is a core region of the auditory cortex whose morphology is highly variable across individuals. This variability has been linked to sound perception ability in both speech and music domains. Previous studies show that variations in morphological features of HG, such as cortical surface area and thickness, are heritable. To identify genetic variants that affect HG morphology, we conducted a genome-wide association scan (GWAS) meta-analysis in 3054 healthy individuals using HG surface area and thickness as quantitative traits. None of the single nucleotide polymorphisms (SNPs) showed association P values that would survive correction for multiple testing over the genome. The most significant association was found between right HG area and SNP rs72932726 close to gene DCBLD2 (3q12.1; P=2.77 * 10(-7) ). This SNP was also associated with other regions involved in speech processing. The SNP rs333332 within gene KALRN (3q21.2; P=2.27 * 10(-6) ) and rs143000161 near gene COBLL1 (2q24.3; P=2.40 * 10( 6) ) were associated with the area and thickness of left HG, respectively. Both genes are involved in the development of the nervous system. The SNP rs7062395 close to the X-linked deafness gene POU3F4 was associated with right HG thickness (Xq21.1; P=2.38 * 10(-6) ). This is the first molecular genetic analysis of variability in HG morphology. PMID- 25130325 TI - Systematic review: internet-based program for youth smoking prevention and cessation. AB - PURPOSE: To review the characteristics and effects Internet-based youth smoking prevention and cessation programs. DESIGN: Systematic review of published articles in peer-reviewed journals in the past 10 years, focused on Internet based youth smoking prevention and cessation programs. METHODS: Twelve articles were selected based on the following criteria: studies reporting the outcomes of Internet-based smoking cessation or prevention intervention programs for adolescents who are younger than 24 years. FINDINGS: The components of youth Internet-based smoking intervention programs are analyzed based on study features (i.e., sample, design, theoretical basis, analysis, outcome measures) and program characteristics (i.e., focus, setting, frequency, duration, intensity, and different components) that make the programs effective. The most common components of effective Internet-based programs are identified as the following: the use of multimedia, tailored approaches, personalized feedback, and interactive features. CONCLUSIONS: The characteristics and effects of the programs vary, but most programs show positive results in youth smoking prevention and cessation in spite of the studies' limitations. CLINICAL RELEVANCE: The evidence from this review provides useful information of recent efforts related to Internet-based youth smoking prevention and cessation programs, which can have significant clinical implications in developing future innovative youth smoking prevention and intervention programs. PMID- 25130326 TI - Graft rejection and failure following endothelial keratoplasty (DSAEK) and penetrating keratoplasty for secondary endothelial failure. AB - PURPOSE: To compare the frequency of rejection and graft failure after Descemet's stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) for secondary endothelial failure. METHODS: Seventy-eight eyes undergoing DSAEK from 2006 to 2013 and 80 eyes undergoing PK from 1998 to 2013 were included. Indications were endothelial failure due to pseudophakic bullous keratopathy (82%), previous eye trauma (8%), uveitis (4%) or other causes (6%). Rejection episodes and graft failure were recorded, together with preoperative risk factors (glaucoma, neovascularization and active inflammation). Kaplan-Meier survival curves with up to 4 years follow-up were used to compare DSAEK with PK, as well as low-risk with high-risk eyes. RESULTS: During follow-up, 15% of the PK treated eyes and 4% of the DSAEK-treated eyes experienced rejection. Graft failure occurred in 8% of the PK-treated eyes and in 7% of the DSAEK-treated eyes. No significant differences were found in the rate of rejection (p=0.11), graft failure (p=0.29) or rejection-related graft failure (p=0.30) between DSAEK and PK in low-risk eyes. In DSAEK, high-risk eyes (mainly with glaucoma) experienced significantly more rejection episodes (p=0.01), graft failures (p=0.04) and rejection-related graft failures (p=0.04) compared with low-risk eyes. No differences were seen between high-risk and low-risk PK-treated eyes (p>0.40). CONCLUSION: In the present, relatively small study, no differences in rejection rate or graft failure were found between DSAEK and PK in low-risk eyes. However, glaucoma seems to increase the risk of graft complications after DSAEK for secondary endothelial failure. Long-term studies of larger samples sizes are needed to confirm this. PMID- 25130327 TI - Can platelet count and mean platelet volume during the first trimester of pregnancy predict preterm premature rupture of membranes? AB - AIM: The aim of our study was to evaluate the values of platelet count and mean platelet volume (MPV) obtained from maternal serum during the first trimester to predict subsequent preterm premature rupture of membranes (PPROM). MATERIAL AND METHODS: The records of 318 women with PPROM and 384 healthy controls in a single center between 2009 and 2013 were retrospectively evaluated. Platelet count and MPV values between 7 and 14 weeks of gestation were compared. Receiver-operator curve analysis was performed to identify the optimal platelet count and MPV cut off levels predicting PPROM. RESULTS: Compared with controls, women with PPROM had significantly increased levels of platelet count and significantly decreased levels of MPV in the first trimester (P < 0.001). The area under the receiver operator curve was 0.642 for MPV and 0.579 for platelet count. The cut-off values of MPV <= 8.6 fL and platelet count >=216 * 10(3) /MUL predicted PPROM with a sensitivity of 58% and 65% and specificity of 62% and 44%, respectively. CONCLUSION: MPV can be used as a more efficient predictor for an early diagnosis of PPROM than platelet count. However, further research combining other markers is needed to increase the efficiency of prediction. PMID- 25130329 TI - NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles. AB - The design of nanoplatforms with target recognition and near-infrared (NIR) laser photoregulated chemo- and photodynamic therapy is highly desirable but remains challenging. In this work, we have developed such a system by taking advantage of a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles (UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX) through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser irradiation, the UCNPs emit UV and visible light. The up-converted UV light is utilized for controlled drug release through the photocleavage of the ortho nitrobenzyl linker, while the up-converted visible light is used to initiate the polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS generation and controlled drug release in cancer cells upon single laser irradiation. In addition, the combination therapy showed enhanced inhibition of U87-MG cell growth as compared to sole treatments. As two light sources with different wavelengths are always needed for traditional photodynamic therapy and photoregulated drug release, the adoption of UCNPs as an NIR light switch is highly beneficial to combined chemo- and photodynamic therapy with enhanced therapeutic effects. PMID- 25130328 TI - Interferon regulatory factor 3 as key element of the interferon signature in plasmacytoid dendritic cells from systemic lupus erythematosus patients: novel genetic associations in the Mexican mestizo population. AB - Many genetic studies have found an association between interferon regulatory factors (IRF) single nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE); however, specific dendritic cell (DC) alterations have not been assessed. The aim of the present study was to address the expression of IRF3 and IRF5 on different DC subsets from SLE patients, as well as their association with interferon (IFN)-alpha production and novel SNPs. For the genetic association analyses, 156 SLE patients and 272 healthy controls from the Mexican mestizo population were included. From these, 36 patients and 36 controls were included for functional analysis. Two IRF3 SNPs - rs2304206 and rs2304204 - were determined. We found an increased percentage of circulating pDC in SLE patients in comparison to controls (8.04 +/- 1.48 versus 3.35 +/- 0.8, P = 0.032). We also observed enhanced expression of IRF3 (64 +/- 6.36 versus 36.1 +/- 5.57, P = 0.004) and IRF5 (40 +/- 5.25 versus 22.5 +/- 2.6%, P = 0.010) restricted to this circulating pDC subset from SLE patients versus healthy controls. This finding was associated with higher IFN-alpha serum levels in SLE (160.2 +/- 21 versus 106.1 +/- 14 pg/ml, P = 0.036). Moreover, the IRF3 rs2304206 polymorphism was associated with increased susceptibility to SLE [odds ratio (OR), 95% confidence interval (CI) = 2.401 (1.187-4.858), P = 0.021] as well as enhanced levels of serum type I IFN in SLE patients who were positive for dsDNA autoantibodies. The IRF3 rs2304204 GG and AG genotypes conferred decreased risk for SLE. Our findings suggest that the predominant IRF3 expression on circulating pDC is a key element for the increased IFN-alpha activation based on the interplay between the rs2304206 gene variant and the presence of dsDNA autoantibodies in Mexican mestizo SLE patients. PMID- 25130330 TI - Cryopreserved platelets: frozen in a logjam? PMID- 25130331 TI - Chikungunya virus: new risk to transfusion safety in the Americas. PMID- 25130332 TI - Transfusion medicine illustrated. An allergic transfusion reaction with angioedema. PMID- 25130333 TI - Apples, oranges, and autotransfusion techniques. PMID- 25130334 TI - In reply. PMID- 25130336 TI - Coagulation values in extreme premature infants. PMID- 25130335 TI - Safety measures to prevent hepatitis E virus transmission by blood transfusion. PMID- 25130337 TI - Obesity. AB - This narrative symposium was inspired by the American Medical Associations (AMA) decision to label obesity a disease. How do people who have been classified as obese feel this decision impacts on their lives? Personal narrative authors offer their experiences with obesity and healthcare. The symposium also hosts five commentary articles from scholars and stakeholders with a wide range of perspectives. These articles pull from themes in the personal narratives and bring them into dialogue with the current scholarly literature on this topic. PMID- 25130338 TI - I am not obese. I am just fat. PMID- 25130339 TI - Experiences of an obese patient. PMID- 25130340 TI - Shame is not an effective diet plan. PMID- 25130341 TI - Little body hidden within. PMID- 25130342 TI - My story: evolving obesities. PMID- 25130343 TI - Explode and die! A fat woman's perspective on prenatal care and the fat panic epidemic. PMID- 25130344 TI - Fitness, fatness, and aesthetic judgments of the female body: what the AMA decision to medicalize obesity means for other non-normal female bodies. PMID- 25130345 TI - Obesity treatment: one size does not fit all. PMID- 25130346 TI - Stepping off the edge of the earth: a bariatric patient's journey out of obesity. PMID- 25130347 TI - I'm Your Patient, Not a Problem. PMID- 25130348 TI - Journey to wellness. PMID- 25130349 TI - Obesity as disease: definition by desperation. PMID- 25130350 TI - Fatness, medicalization, and stigma: on the need to do better. AB - This article comments on a collection of remarkable narratives authored by fat writers addressing the American Medical Association's decision to label obesity a disease. Endeavoring to avoid what has been termed "thinsplaining," the commentary examines the voices of the writers in the hopes of identifying key themes and points that emerge from these fat narratives. The commentary canvasses the writers' perspectives on topics such as the medicalization and pathologization of fat, the Western and especially American tendency to emphasize individual culpability for fatness, and, of course, the horrific commonality and intensity of fat stigma. Stigma is a particular focus for the commentary, both because it is a principal theme in the collection, and also because it is important to understand precisely what stigma is and its deep connections to larger macrosocial structures. The commentary concludes with a simple admonition, gleaned from the narratives: we should strive to do better. PMID- 25130351 TI - When one size does not fit all: a commentary. AB - This commentary explores a few of the common threads in a symposium of obesity narratives in light of the American Medical Association's classification of obesity as a disease. While the narratives illustrate the breadth of experiences, they each highlight the absence of a clear approach for the treatment of obesity, as well as the lack of conversation and compassion in the most basic of interactions with medical professionals. This could be cause for despair, yet we learn through these shared experiences that we can take control of our care and plot a course for real and lasting assistance with this condition. PMID- 25130352 TI - The burden of obesity: personal stories, professional insights. AB - The word obesity invokes multiple connotations that contain a realm of disparate descriptions ranging from disease to disdain. There are also few other human conditions that cause increased morbidity and mortality and affect millions of individuals worldwide yet is still viewed by many as a character fault or moral failure. Herein we have the opportunity to read the personal reflections of individuals with obesity who have struggled with their weight over a lifetime. Through a series of 12 narratives, the authors collectively share their shame, humiliation, dignity, inner strength and advice for health professionals who they entrust. PMID- 25130353 TI - Die another day: the obstacles facing fat people in accessing quality healthcare. AB - In this issue of Narrative Inquiries in Bioethics, fat individuals share their healthcare experiences. Through reading the narratives, it becomes clear that access to proper healthcare is often blocked for fat patients by a variety of things, including shame and fat stigma. From physical spaces in which they do not fit, to doctors who diagnose all of their problems as 'fat', similar themes are echoed across the stories. And common are the refrains for better treatment, less shame, and access to evidenced based care from educated providers. In this manuscript, I highlight common themes from the stories and integrate them with themes from the literature. I allow the two dissenting narratives to suggest other ways of thinking about fatness and well-being. And I conclude by suggesting ways to provide better access to quality healthcare for fat individuals. PMID- 25130354 TI - Risk factor medicalization, hubris, and the obesity disease. AB - The essays on obesity in this issue frequently refer to the recent American Medical Association (AMA) declaration of obesity as a disease. In response to these essays, I describe and explore the significance of 'risk-factor medicalization' and how negative unintended consequences with this approach to disease modeling are exemplified in many of the essays. I also relate the essays' content to the issue of physician hubris in the face of their own helplessness in aiding the obese patient. PMID- 25130355 TI - Stories worth telling: moral experiences of suicidal behavior. AB - Moral constructions of suicide are deliberately avoided in contemporary suicidology, yet morality persists, little or imperfectly acknowledged, in its practices and in the policies, discourses, and instruments that it underpins. This study used narrative methodologies to examine the normative force of suicidology and its implications for persons who had engaged in an act of nonfatal suicidal behavior. I interviewed a convenience sample of twelve persons from two inner-urban community mental health centers who were receiving crisis and case management services after a recent act of nonfatal suicidal behavior. Interviews focused on events leading up to and after participants' suicidal behavior; the responses their suicidal behavior generated in others, including family, friends, and the health professionals caring for them; and cultural views of suicide more broadly. Analysis of these interviews revealed that, although participants' narratives were broadly consistent with a number of recognizable, canonical story formats common to our cultural repertoire of stories of suicide, they also revealed important tensions, divisions, conflicts, and challenges to contemporary suicidological discourse and practice. Despite evidence to suggest that biomedical understandings of suicide provided some therapeutic benefit to participants, they did not address important social and moral dimensions of human life or explore their connection to suicidal behavior-aspects of the suicidal event that were critical to its causation and to its retelling and "resolution." The results of this study provide important insights into the moral features of suicidal behavior, the moral and ethical implications of suicide research, and the limitations of moral and ethical discourse in suicidology. PMID- 25130356 TI - Desperately seeking a surrogate - for a patient lacking decision-making capacity. AB - Our hospital's policy and procedures for "Patients Without Surrogates" provides for gradated safeguards for managing patients' treatment and care when they lack decision-making capacity, have no advance directives, and no surrogate decision makers are available. The safeguards increase as clinical decisions become more significant and have greater consequences for the patient. The policy also directs social workers to engage in "rigorous efforts" to search for surrogates who can potentially provide substituted judgments for such patients. We describe and illustrate the policy, procedures, and kinds of expected rigorous efforts through our narration of an actual but disguised case for which we provided clinical ethics guidance and social work expertise. Our experience with and reflection on this case resulted in four recommendations we make for health care facilities and organizations that aim to provide quality care for their own patients without surrogates. PMID- 25130357 TI - Dax's case redux: when comes the end of the day? AB - Forty years after Dax Cowart fought to have his voice heard regarding his medical treatment, patient autonomy and rights are at the heart of patient care today. Yet, despite its centrality in patient care, the tension between a severely burned patient's right to stop treatment and the physician's role in saving a life has not abated. As this case study explores, barriers remain to hearing and respecting a patient's treatment decisions. Dismantling these barriers involves dispelling the myths that burn patients must grin and bear intense pain to recover and that a patient's choice to discontinue treatment equals physician failure. Moreover, in these situations, sustained, direct engagement between physician and patient can reduce the moral distress of all involved and enable physicians to hear and better accept when a patient is calling for the end of the day. PMID- 25130358 TI - Undocumented and at the end of life. AB - Three of the most contentious issues in contemporary American society-allocation of medical resources, end of life care, and immigration-converge when undocumented immigrant patients are facing the terminal phase of chronic illness. The lack of consistent, pragmatic policy in each of these spheres leaves us with little guidance for how to advocate for undocumented patients at the end of life. Limited resources and growing need compound the problem. Care for patients in this unfortunate situation should be grounded in clinical and economic reality as well as respect for the dignity of the individual to avoid exacerbating inequalities. PMID- 25130359 TI - Calling obesity a disease is a terrible decision. PMID- 25130360 TI - The weight I just can't lose. PMID- 25130361 TI - You mean it's not my fault: learning about lipedema, a fat disorder. PMID- 25130362 TI - Editors' note. PMID- 25130363 TI - The ZnSn(OH)6 nanocube-graphene composite as an anode material for Li-ion batteries. AB - ZnSn(OH)6 (ZSH) nanocubes with a uniform size of 40-80 nm were synthesized by using a simple hydrothermal route and then combined with graphene sheets (rGO) via the electrostatic interaction. The formed composite of ZnSn(OH)6 nanocube graphene (ZSH-rGO) was used as an anode material for Li-ion batteries and it exhibited significantly enhanced electrochemical performance. For instance, a capacity of 540 mA h g(-1) at 500 mA g(-1) was retained after 40 cycles. PMID- 25130364 TI - A comparison of four gutta-percha filling techniques in simulated C-shaped canals. AB - AIM: To compare four gutta-percha filling techniques in simulated C-shaped canals based on filling quality at three cross-sectional levels, filling time and the apical extrusion of gutta-percha. METHODOLOGY: Forty resin simulated C-shaped canals were constructed and filled using one of four techniques: cold lateral compaction (LC), ultrasonic compaction (UC), single cone with injectable gutta percha (Obtura II(TM) ) (IT) and core-carrier (Thermafil((r)) ) (CC). Cross sections were made at 1 (L1), 3 (L3) and 6 (L6) mm from the canal terminus. Areas of gutta-percha, sealer and voids in each cross section were measured using an image analysis system. Data were analysed using a univariate general linear model and post hoc test (Dunnett's T3). Data on time taken to fill canals was evaluated using the Bonferroni post hoc test. RESULTS: CC had more gutta-percha and less sealer compared with IT at L1 (P < 0.05). LC had marginally significantly less gutta-percha than CC at this level (P = 0.049). At level 3 mm, significantly more gutta-percha and less sealer were present in IT compared with LC (P < 0.05). The techniques showed no difference in quality at L6. The time for LC (20.72 min) was three times longer than for both IT (6.11 min) and CC (6.67 min), whereas for UC (26.92 min), it was four times longer (P < 0.001). Finally, the four techniques were not different in the occurrence of apical extrusion of gutta-percha. CONCLUSIONS: The core-carrier technique was the most effective technique when assessed by gutta-percha area in this simulated C-shaped canal. PMID- 25130365 TI - M2(m-dobdc) (M = Mg, Mn, Fe, Co, Ni) metal-organic frameworks exhibiting increased charge density and enhanced H2 binding at the open metal sites. AB - The well-known frameworks of the type M2(dobdc) (dobdc(4-) = 2,5-dioxido-1,4 benzenedicarboxylate) have numerous potential applications in gas storage and separations, owing to their exceptionally high concentration of coordinatively unsaturated metal surface sites, which can interact strongly with small gas molecules such as H2. Employing a related meta-functionalized linker that is readily obtained from resorcinol, we now report a family of structural isomers of this framework, M2(m-dobdc) (M = Mg, Mn, Fe, Co, Ni; m-dobdc(4-) = 4,6-dioxido 1,3-benzenedicarboxylate), featuring exposed M(2+) cation sites with a higher apparent charge density. The regioisomeric linker alters the symmetry of the ligand field at the metal sites, leading to increases of 0.4-1.5 kJ/mol in the H2 binding enthalpies relative to M2(dobdc). A variety of techniques, including powder X-ray and neutron diffraction, inelastic neutron scattering, infrared spectroscopy, and first-principles electronic structure calculations, are applied in elucidating how these subtle structural and electronic differences give rise to such increases. Importantly, similar enhancements can be anticipated for the gas storage and separation properties of this new family of robust and potentially inexpensive metal-organic frameworks. PMID- 25130367 TI - Edge effects in the primate community of the biological dynamics of Forest Fragments Project, Amazonas, Brazil. AB - While much is known about abiotic and vegetative edge effects in tropical forests, considerably less is known about the impact of forest edges on large mammals. In this study, we examine edge effects in a primate community to determine: 1) the distance from the edge over which edge effects in primate density are detectable, 2) whether individual species exhibit edge effects in their density, and 3) whether biological characteristics can be used to predict primate presence in edge habitats. Given their importance to many primate species, we also examine the influence of the number of large trees. We found edge penetration distances of 150 m for the five species that experienced edge effects, suggesting that primates respond to edge-related changes in the plant community that are known to be strongest over the first 150 m. Four species had higher edge densities: Alouatta macconnelli (folivore-frugivore), Chiropotes chiropotes (frugivorous seed predator), Saguinus midas (frugivore-faunivore), and Sapajus apella apella (frugivore-faunivore); one species' density was lower: Ateles paniscus (frugivore); and the final species, Pithecia chrysocephala (frugivorous seed predator), did not show an edge-related pattern. The lone significant relationship between the biological characteristics examined (body weight, diet, group size, and home range size) and primate presence in edge habitats was a negative relationship with the amount of fruit consumed. Though we did not examine primate responses to edges that border a denuded matrix, we have shown that edges influence primate distribution even following decades of secondary forest regeneration at habitat edges. PMID- 25130366 TI - Quantitative super-resolution imaging of Bruchpilot distinguishes active zone states. AB - The precise molecular architecture of synaptic active zones (AZs) gives rise to different structural and functional AZ states that fundamentally shape chemical neurotransmission. However, elucidating the nanoscopic protein arrangement at AZs is impeded by the diffraction-limited resolution of conventional light microscopy. Here we introduce new approaches to quantify endogenous protein organization at single-molecule resolution in situ with super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM). Focusing on the Drosophila neuromuscular junction (NMJ), we find that the AZ cytomatrix (CAZ) is composed of units containing ~137 Bruchpilot (Brp) proteins, three quarters of which are organized into about 15 heptameric clusters. We test for a quantitative relationship between CAZ ultrastructure and neurotransmitter release properties by engaging Drosophila mutants and electrophysiology. Our results indicate that the precise nanoscopic organization of Brp distinguishes different physiological AZ states and link functional diversification to a heretofore unrecognized neuronal gradient of the CAZ ultrastructure. PMID- 25130369 TI - Decline in self-reported health (EQ-5D) over time after surgical reconstruction of the right ventricular outflow tract: a longitudinal cohort study of 103 patients. AB - OBJECTIVE: Patients with congenital heart disease may be operated with surgical reconstruction of the right ventricular outflow tract (RVOT). Reintervention is common in this group of patients. The aim of this study was to examine longitudinal self-reported health measured by the EQ-5D questionnaire. DESIGN: Data were collected from the Swedish Registry of Congenital Heart Disease. EQ-5D, which measures health outcome, was introduced into the registry in 2005. All adult patients with previous surgical reconstruction of the RVOT who had EQ-5D data from their first and latest visit were analyzed. RESULTS: Among 103 patients (65 male and 38 female), mean age 31 (range 19-78 years), the diagnoses were: tetralogy of Fallot (n = 66); truncus, transpositions, and double outlet right ventricle (n = 23); and Ross-operated congenital aortic valve disease (n = 14). Time from first to latest visit was 3 years (range 1-7 years). Eighteen patients underwent 26 reinterventions in the observational period from the first to latest visit, including operations, percutaneous interventions, pacemaker implantations, and ablations. Health perception, mean EQ-5D visual analog scale, VAS, declined from 84.4 (standard deviation (SD) = 14.6) to 78.6 (SD = 18.3) at the latest visit, P = .001. The decline is almost exclusively seen in patients without reinterventions. Low EQ-VAS was associated with symptoms and New York Heart Association class II-IV. Patient-reported problems in the EQ-5D dimension usual activities were more common in the patients having reinterventions (25%) than those without reintervention (7%), P = .04. CONCLUSION: In this longitudinal cohort study of patients with previous surgical reconstruction of the RVOT, health perception declined over time. The decline was not observed in patients undergoing any additional interventions. PMID- 25130368 TI - Examining gender difference in adult-onset psychosis in Hong Kong. AB - AIM: Gender-specific treatment strategies for psychosis have been suggested in recent years. Data on gender difference were largely consistent regarding premorbid functioning, age of onset and negative symptoms; however, results regarding neurocognitive function and duration of untreated psychosis were mixed and inconclusive. In this study, we aimed at a thorough examination on the gender differences in 360 Chinese patients with first-episode psychosis in Hong Kong. METHODS: From June 2009 to August 2011, participants were consecutively recruited from a population-based territory-wide study of early psychosis targeting first episode psychosis in Hong Kong. Comprehensive data on basic demographics, premorbid functioning and schizoid and schizotypal traits, clinical, functioning, medication side effects and a battery of neurocognitive measures were collected upon entry into the service. RESULTS: In 360 patients with first-episode psychosis aged between 26 and 55 years, 43.6% (n = 157) were male and 56.4% (n = 203) were female. Males had poorer premorbid functioning and adjustment, earlier age of onset, more negative symptoms and poorer functioning in terms of work productivity, independent living and immediate social network relationships at presentation of first-episode psychosis. Interestingly, our data indicate that males tend to be more educated, and also characterized by higher IQ, better neurocognitive performance on visual domain compared with females. Duration of untreated psychosis was not different between the two genders. CONCLUSION: Data from this homogeneous cohort of Chinese populations enabled tailored and culturally sensitive recommendation on gender-specific treatment strategies, hence improving patients' care and facilitate better diagnostic and interventional decisions for patients with psychosis. PMID- 25130370 TI - Validation of a field based chromatin dispersion assay to assess sperm DNA fragmentation in the bottlenose dolphin (Tursiops truncatus). AB - Over the last two decades, there have been significant advances in the use of assisted reproductive technology for genetic and reproductive management of captive dolphin populations, including evaluation of sperm DNA quality. This study validated a customized sperm chromatin dispersion test (SCDt) for the bottlenose dolphin (Tursiops truncatus) as a means of assessing sperm DNA damage both in the field and in the laboratory. After performing the SCDt, two different sperm morphotypes were identified: (i) sperm with fragmented DNA showed large haloes of dispersed DNA fragments emerging from a compact sperm nucleoid core and (ii) sperm containing non-fragmented DNA displayed small compact haloes surrounded by a dense core of non-dispersed DNA and protein complex. Estimates of sperm DNA fragmentation by means of SCDt were directly comparable to results obtained following a two-tailed comet assay and showed a significant degree of correlation (r = 0.961; p < 0.001). This investigation also revealed that the SCDt, with minor modifications to the standard protocol, can be successfully conducted in the field using a LED florescence microscopy obtaining a high correlation (r = 0.993; p = 0.01) between the data obtained in the laboratory and in the field. PMID- 25130372 TI - Extracellular DNA traps in bronchoalveolar fluid from a murine eosinophilic pulmonary response. AB - Asthma is associated with a loss of the structural integrity of airway epithelium and dysfunction of the physical barrier, which protects airways from external harmful factors. Granulocyte activation causes the formation of extracellular traps, releasing web-like structures of DNA and proteins, being important to kill pathogens extracellularly. We investigated whether eosinophils infiltrating airways in an experimental model of asthma would induce eosinophil extracellular traps (EETs) in bronchoalveolar lavage fluid and lung tissue. We showed that an ovalbumin (OVA) asthma protocol presented a significant increase in eosinophil counts with increased extracellular DNA in bronchoalveolar lavage fluid as well as in lung tissue, confirming the presence of DNA traps colocalized with eosinophil peroxidase. EETs formation was reversed by DNase treatment. With these approaches, we demonstrated for the first time that OVA-challenged mice release extracellular DNA traps, which could aggravate pulmonary dysfunction. PMID- 25130371 TI - miR-338-3p is over-expressed in blood, CFS, serum and spinal cord from sporadic amyotrophic lateral sclerosis patients. AB - Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Ninety percent of ALS patients are sporadic cases (sALS) with no clear genetic linkage. Accumulating evidence indicates that various microRNAs (miRNAs), expressed in a spatially and temporally controlled manner in the brain, play a key role in neuronal development. In addition, microRNA dysregulation contributes to some mental disorders and neurodegeneration diseases. In our research, the expression of one selected miRNA, miR-338-3p, which previously we have found over-expressed in blood leukocytes, was studied in several different tissues from sALS patients. For the first time, we detected a specific microRNA disease-related upregulation, miR-338-3p, in blood leukocytes as well in cerebrospinal fluid, serum, and spinal cord from sALS patients. Besides, staining of in situ hybridization showed that the signals of miR-338-3p were localized in the grey matter of spinal cord tissues from sALS autopsied patients. We propose that miRNA profiles found in tissue samples from sALS patients can be relevant to understand sALS pathogenesis and lead to set up effective biomarkers for sALS early diagnosis. PMID- 25130373 TI - Resource loss, self-efficacy, and family support predict posttraumatic stress symptoms: a 3-year study of earthquake survivors. AB - BACKGROUND AND OBJECTIVES: Social support and self-efficacy are regarded as coping resources that may facilitate readjustment after traumatic events. The 2009 Cinchona earthquake in Costa Rica serves as an example for such an event to study resources to prevent subsequent severity of posttraumatic stress symptoms. DESIGN: At Time 1 (1-6 months after the earthquake in 2009), N=200 survivors were interviewed, assessing resource loss, received family support, and posttraumatic stress response. At Time 2 in 2012, severity of posttraumatic stress symptoms and general self-efficacy beliefs were assessed. METHODS: Regression analyses estimated the severity of posttraumatic stress symptoms accounted for by all variables. Moderator and mediator models were examined to understand the interplay of received family support and self-efficacy with posttraumatic stress symptoms. RESULTS: Baseline posttraumatic stress symptoms and resource loss (T1) accounted for significant but small amounts of the variance in the severity of posttraumatic stress symptoms (T2). The main effects of self-efficacy (T2) and social support (T1) were negligible, but social support buffered resource loss, indicating that only less supported survivors were affected by resource loss. Self-efficacy at T2 moderated the support-stress relationship, indicating that low levels of self-efficacy could be compensated by higher levels of family support. Receiving family support at T1 enabled survivors to feel self efficacious, underlining the enabling hypothesis. CONCLUSIONS: Receiving social support from relatives shortly after an earthquake was found to be an important coping resource, as it alleviated the association between resource loss and the severity of posttraumatic stress response, compensated for deficits of self efficacy, and enabled self-efficacy, which was in turn associated with more adaptive adjustment 3 years after the earthquake. PMID- 25130375 TI - A quantitative evaluation method using processed optical images and analysis of age-dependent changes on nasolabial lines. AB - BACKGROUND/PURPOSE: Nasolabial lines (NL) and wrinkles of the face are major features of aging. Wrinkles have been studied widely by morphological methods using 3-dimensional (3D) photographic analysis instrument, but NL were evaluated by visual scoring usually. To evaluate NL quantitatively, another method is needed. This study is purposed to find out quantitative method for evaluation of NL. METHOD: One hundred Korean female subjects aged 20 to 60 were recruited in this study. Facial image was taken using light source adjusted VISIA-CR((r)) and 3-dimensional wrinkle depth on the NL area was evaluated by Phase shift rapid in vivo measuring of human skin (PRIMOS((r))). The pixel number of NL area and the angle were obtained using processed images. The severity of NL was assessed by visual score. Skin elasticity was measured by Cutometer((r)) MPA580. Statistical significance was determined at P < 0.05. RESULT: The optical images obtained by light source adjusted VISIA-CR((r)) were easy to distinguish NL and significantly increased age-dependently. And three parameters of elasticity (R2, R5, and R7) on NL area were gradually decreased with age. The Pearson correlation coefficient was -0.756 (P < 0.01) between R7 parameter and ages. Also the pixel number of NL area, angle, wrinkle depth on the NL area (Ra), and visual score were decreased elasticity-dependently. The pixel number of NL area was highly related to Ra (r = 0.567, P < 0.01) and visual score (r = 0.647, P < 0.01). CONCLUSION: This study has shown that NL severity is related to decrease of dermal elasticity and age using quantitative new method by processing optical images. PMID- 25130376 TI - TGFbeta1 increases microglia-mediated engulfment of apoptotic cells via upregulation of the milk fat globule-EGF factor 8. AB - Milk fat globule-epidermal growth factor-factor 8 (Mfge8) has been described as an essential molecule during microglia-mediated clearance of apoptotic cells via binding to phosphatidylserine residues and subsequent phagocytosis. Impaired uptake of apoptotic cells by microglia results in prolonged inflammatory responses and damage of healthy cells. Although the mechanisms of Mfge8-mediated engulfment of apoptotic cells are well understood, endogenous or exogenous factors that regulate Mfge8 expression remain elusive. Here, we describe that TGFbeta1 increases the expression of Mfge8 and enhances the engulfment of apoptotic cells by primary mouse microglia in a Mfge8-dependent manner. Further, apoptotic cells are capable of increasing microglial TGFbeta expression and release and shift the microglia phenotype toward alternative activation. Moreover, we provide evidence that Mfge8 expression is differentially regulated in microglia after classical and alternative activation and that Mfge8 is not able to exert direct antiinflammatory effects on LPS-treated primary microglia. Together, these results underline the importance of TGFbeta1 as a regulatory factor for microglia and suggest that increased TGFbeta1 expression in models of neurodegeneration might be involved in clearance of apoptotic cells via regulation of Mfge8 expression. PMID- 25130374 TI - Bacteriology of pressure ulcers in individuals with spinal cord injury: What we know and what we should know. AB - Individuals with spinal cord injury (SCI) are at increased risk for the development of pressure ulcers. These chronic wounds are debilitating and contribute to prolonged hospitalization and worse medical outcome. However, the species of bacteria and the role that specific species may play in delaying the healing of chronic pressure ulcers in the SCI population has not been well characterized. This study will review the literature regarding what is known currently about the bacteriology of pressure ulcers in individuals with SCI. An electronic literature search of MEDLINE (1966 to February 2014) was performed. Eleven studies detailing bacterial cultures of pressure ulcers in the SCI population met inclusion criteria and were selected for review. Among these studies, bacterial cultures were often polymicrobial with both aerobic and anaerobic bacteria identified with culture techniques that varied significantly. The most common organisms identified in pressure ulcers were Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, and Enterococcus faecalis. In general, wounds were poorly characterized with minimal to no physical description and/or location provided. Our present understanding of factors that may alter the microbiome of pressure ulcers in individuals with SCI is quite rudimentary, at best. Well-designed studies are needed to assess appropriate wound culture technique, the impact of bacterial composition on wound healing, development of infection, and the optimum medical and surgical approaches to wound care. PMID- 25130377 TI - The significance of p40 expression in sclerosing hemangioma of lung. AB - To explore the histogenesis of cuboidal and polygonal tumor cells in the sclerosing hemangioma of lung (SHL), eighteen cases of SHL were retrospectively studied. SPB, p40, TTF-1,EMA,CKpan, vimentin,SMA, CgA,Syn and CD34 were immunohistochemically labeled by the EnVisionmethod. It was found that the four main types of structure in SHL were solid,papillary, hemorrhagic and sclerotic patterns. The tumor cells were composed mainly of two types of cells: cuboidal tumor cells and polygonal tumor cells. The immunohistochemistry showed that p40 was expressed only in cuboidal tumor cells. TTF-1 and EMA were expressed in both polygonal cells and cuboidal cells. SPB was also expressed in cuboidal tumor cells; vimentin was expressed in all polygonal tumor cells and some cuboidal cells. The findings suggest that the p40-positive cuboidal tumor cells may be pluripotent original respiratory epithelial cells, with multi-directional differentiation capacity. PMID- 25130378 TI - Evidence of inbreeding depression on height, weight, and body mass index: a population-based child cohort study. AB - OBJECTIVE: The study was aimed to estimate the effect of inbreeding on height, weight, and body mass index (BMI) in comparison with non-inbred children. METHODS: A cohort study was conducted during April 2013 through July 2013 in Jammu (North India) and a total of 1,270 children (5-15 years of age) were selected in a random way both from inbred and non-inbred families of five Muslim populations. The height and weight was measured using standard methods and the BMI categories were employed as adapted by World Health Organization (WHO). Family pedigrees were drawn to access the family history and children's inbred status in terms of coefficient of inbreeding (F). RESULTS: Children of inbred families showed decline in mean value for height, weight, and BMI (P < 0.0001). The mean difference (95% confidence interval) in height -7.318 (5.827-8.809), weight -6.590 (5.100-8.081) and BMI -2.133 (0.6419-3.624) for inbred as compared with non-inbred children were found to be significant (P < 0.001). We observed an increase in the difference in mean values for height, weight and BMI with the increase of inbreeding coefficient and these were statistically significant (P < 0.05, using post hoc tests). The frequency of underweight children was found to be higher among individuals in the inbred category (<18.5 kg/m(2) = 47.31%) as compared with the non-inbred category (<18.5 kg/m(2) = 13.41%) and subsequent depression was found among the inbred children due to an increase of inbreeding coefficient. CONCLUSIONS: Our results provide the evidence of inbreeding depression on height, weight, and BMI being important in context of child health. PMID- 25130379 TI - Mononuclear and terminal zirconium and hafnium methylidenes. AB - The dimethyl aryloxide complexes [(PNP)M(CH3)2(OAr)] (M=Zr or Hf; PNP(-)=N[2 P(CHMe2)2-4-methylphenyl]2); Ar=2,6-iPr2C6H3), which were readily prepared from [(PNP)M(CH3)3] by alcoholysis with HOAr, undergo photolytically induced alpha hydrogen abstraction to cleanly produce complexes [(PNP)M=CH2(OAr)] with terminal methylidene ligands. These unique systems have been fully characterized, including the determination of a solid-state structure in the case of M=Zr. PMID- 25130380 TI - Restrictive food intake as a choice--a paradigm for study. AB - OBJECTIVE: Inadequate intake and preference for low-calorie foods are salient behavioral features of Anorexia Nervosa (AN). The neurocognitive mechanisms underlying pathological food choice have not been characterized. This study aimed to develop a new paradigm for experimentally modeling maladaptive food choice in AN. METHOD: Individuals with AN (n = 22) and healthy controls (HC, n = 20) participated in a computer-based Food Choice Task, adapted for individuals with eating disorders. Participants first rated 43 food images (including high-fat and low-fat items) for Healthiness and Tastiness; an item rated neutral on both blocks was then selected as the Reference item. On each of 42 subsequent trials participants were asked to choose between the food item presented and the Reference item. RESULTS: The AN group was less likely to choose high-fat foods relative to HC, as evidenced both in multilevel logistic regression (z = 2.59, p = .009) and ANOVA (F(1,39) = 7.80, p = .008) analyses. Health ratings influenced choice significantly more in AN relative to HC (z = 2.7, p = .006), and were more related to Taste among AN (chi(2) = 4.10, p = .04). Additionally, taste ratings declined with duration of illness (r = -.50, p = .02). DISCUSSION: The Food Choice Task captures the preference for low-fat foods among individuals with AN. The findings suggest that the experience of tastiness changes over time and may contribute to perpetuation of illness. By providing an experimental quantitative measure of food restriction, this task opens the door to new experimental investigations into the cognitive, affective, and neural factors contributing to maladaptive food choices characteristic of AN. PMID- 25130384 TI - Surgery for non-small cell lung cancer in younger patients: what are the differences? AB - BACKGROUND: Non-small cell lung cancer (NSCLC) in young adults is uncommon. The objective of this study was to evaluate the clinicopathological characteristics, outcomes and prognosis of people younger than 50 years old treated surgically for NSCLC. METHODS: A retrospective study was conducted using the institutional database of four thoracic surgery units to collect patients with NSCLC younger than 50 years who had undergone surgery. These patients were compared with older patients (>75-years) operated in the same institutions and in the same period. RESULTS: We identified 113 young patients and 347 older patients. Younger patients were more likely to be female, non-smokers, with fewer comorbidities. Younger patients were more likely to be symptomatic at the time of diagnosis. Risk factors for poor prognosis in younger patients were T-stage, and disease free-interval less than 548 days. Kaplan-Meier analysis showed a lower five-year survival in older patients compared with the younger ones (66% vs 38%, p=0.001). CONCLUSIONS: In conclusion NSCLC in younger patients has some distinct clinicopathological characteristics. The overall-survival of young patients is better than in older patients. Young patients receive more complete and aggressive treatment that could explain better survival. Further prospective studies with larger patient populations are required, to clarify the biological and genetic variance of NSCLC in younger patients. PMID- 25130383 TI - Left ventricular geometry and all-cause mortality in advanced age. AB - BACKGROUND: Abnormalities of cardiac structure and function are common in a wide range of populations including those with and without established clinical cardiovascular disease (CVD). This study reports the prevalence of left ventricular hypertrophy (LVH), the four patterns of LV geometry and establishes clinical characteristics and five-year outcomes of each group in people of advanced age. METHOD: A study conducted in general practices and Maori Health Services in three New Zealand North Island locations. One hundred participants had a full clinical echocardiogram performed and analysed in 2008 by one experienced cardiologist blinded to the participant's clinical history. RESULTS: Two-thirds of the participants had CVD. Thirty-two participants had echocardiographic LVH. Those with LVH had higher left atrial area [median (IQR) 26.4cm(2) (10.9) vs. 22.0cm(2) (7.0), p<0.01] and E/e' [median (IQR) 13 (6.8) vs.10.8 (4.1), p=0.01] than those without LVH. Of those with LVH, 10 demonstrated concentric hypertrophy (CH) and 22 eccentric hypertrophy (EH); 12 concentric remodelling (CR) and 40 normal geometry (NG). Both CR and EH were independently associated with higher risk of all-cause mortality (p<0.01) and hospital admissions (p<0.05) than those with NG. Those with EH also had a higher risk of CVD events (p=0.029). CONCLUSIONS: Despite a high prevalence of CVD and hypertension in this sample, half had normal LV geometry. Concentric remodelling and eccentric hypertrophy were associated with higher mortality and adverse CVD outcomes in people of advanced age. PMID- 25130385 TI - Simulation-based ureteroscopy training: a systematic review. AB - OBJECTIVE: Simulation is a common adjunct to operative training and various modalities exist for ureteroscopy. This systematic review aims the following: (1) to identify available ureteroscopy simulators, (2) to explore evidence for their effectiveness using characteristic criterion, and (3) to provide recommendations for simulation-based ureteroscopy training. DESIGN: The preferred reporting items for systematic reviews and meta-analysis statement guidelines were used. A literature search was performed using the PubMed, EMBASE, and Cochrane Library databases. RESULTS: In total, 20 articles concerning ureteroscopy simulators were included. Overall, 3 high-fidelity bench models are available. The Uro-Scopic Trainer has demonstrated face, construct, and concurrent validity, whereas the Scope Trainer has undergone content, construct, and predictive validation. The adult ureteroscopy trainer has demonstrated face, content, and construct validity. The URO Mentor is the only available ureteroscopy virtual-reality system; 10 studies were identified demonstrating its face, content, construct, concurrent, and predictive validity. The Uro-Scopic Trainer, the Scope Trainer, and the URO Mentor have demonstrated high educational impact. A noncommercially available, low-fidelity model has demonstrated effectiveness comparable to its high-fidelity counterpart at 185 times lesser than the price of the Uro-Scopic Trainer. The use of porcine models has also been described in 3 studies but require further study. CONCLUSIONS: Valid models are available for simulation based ureteroscopy training. However, there is a lack of many high-level studies conducted, and further investigation is required in this area. Furthermore, current research focuses on the technical skills acquisition with little research conducted on nontechnical skills acquisition within ureteroscopy. The next step for ureteroscopy training is a formalized and validated curriculum, incorporating simulation, training models, development of nontechnical skills, and real-life practice. PMID- 25130386 TI - Research productivity of residents and surgeons with formal research training. AB - OBJECTIVE: The spectrum of the surgeon-scientist ranges from a clinician who participates in the occasional research collaboration to the predominantly academic scientist with no involvement in clinical work. Training surgeon scientists can involve resource-intense and lengthy training programs, including Masters and PhD degrees. Despite high enrollment rates in such programs, limited data exist regarding their outcome. The aim of the study was to investigate the scientific productivity of general surgeons who completed Masters or PhD graduate training compared with those who completed clinical residency training only. DESIGN: A retrospective cohort study of graduates of general surgery residency was conducted over 2 decades. Data regarding graduation year, dedicated research training type, as well as publication volume, authorship role, and publication impact of surgeons during and after training, were analyzed. SETTING: The study was conducted in 2 general surgery residency training programs in Canada (University of Alberta and University of Toronto). PARTICIPANTS: A cohort of 323 surgeons who completed general surgery residency between 1998 and 2012. RESULTS: Overall, 25% of surgeons obtained graduate-level research degrees. Surgeons with graduate degrees were proportionately more likely to participate in research publications both during training (100% of PhD, 82% of Masters, and 38% of clinical-only graduates, p < 0.05) and after training (91% of PhD, 81% of Masters, and 44% of clinical-only graduates, p < 0.05). Among surgeons involved in publication, the individual publication volume and impact of publication were highest among those with PhD degrees, as compared with clinical-only or Masters training. CONCLUSIONS: The volume and impact of research publication of PhD trained surgeon-scientists are significantly higher than those having clinical only and Masters training. The additional 1 or 2 years of training to obtain a PhD over a Masters degree significantly nurtures trainees to hone research skills within a supervised environment and should be encouraged for research-inclined residents. PMID- 25130387 TI - The right posterior sector graft in living donor liver transplantation revisited. PMID- 25130388 TI - Suboptimal duration of granulocyte colony-stimulating factor use and chemotherapy induced neutropenia in women diagnosed with breast cancer. AB - PURPOSE: Prophylactic use of granulocyte colony-stimulating factor (G-CSF) is recommended for cancer patients who are at high risk of neutropenic events. However, whether the clinical effectiveness of G-CSF from randomized controlled trials translates into "real-world" clinical practice is questionable. The goal of this retrospective cohort study was to examine the impact of G-CSF prophylaxis and other potential risk factors of severe neutropenia in women with breast cancer. METHODS: Our study subjects were women who were diagnosed with breast cancer and who received a new course of chemotherapy between January 1, 2010, and December 31, 2010, at a cancer center in Taiwan. Generalized estimating equations were applied to examine the association between G-CSF prophylaxis and neutropenic events. FINDINGS: We identified 353 women with breast cancer who received a total of 2776 cycles of chemotherapy. G-CSF was used as primary prophylaxis in 7% (n = 202) of cycles and as secondary prophylaxis in 11% (n = 319) of cycles. The mean duration of G-CSF for primary and secondary prophylaxis was 4.9 and 3.7 days, respectively. A chemotherapy regimen with high risk of febrile neutropenia was found to be a risk factor for severe neutropenic events (odds ratio, 3.22 [95% CI, 1.97-5.27]). Prophylactic use of G-CSF was not statistically significantly associated with febrile neutropenia. IMPLICATIONS: The major determinants of neutropenic events among patients with breast cancer were the content and intensity of chemotherapy regimens. Suboptimal use of G-CSF may not be effective in preventing neutropenic events among women with breast cancer. PMID- 25130390 TI - Bioactive nanoparticles stimulate bone tissue formation in bioprinted three dimensional scaffold and human mesenchymal stem cells. AB - Bioprinting based on thermal inkjet printing is a promising but unexplored approach in bone tissue engineering. Appropriate cell types and suitable biomaterial scaffolds are two critical factors to generate successful bioprinted tissue. This study was undertaken in order to evaluate bioactive ceramic nanoparticles in stimulating osteogenesis of printed bone marrow-derived human mesenchymal stem cells (hMSCs) in poly(ethylene glycol)dimethacrylate (PEGDMA) scaffold. hMSCs suspended in PEGDMA were co-printed with nanoparticles of bioactive glass (BG) and hydroxyapatite (HA) under simultaneous polymerization so the printed substrates were delivered with highly accurate placement in three dimensional (3D) locations. hMSCs interacted with HA showed the highest cell viability (86.62 +/- 6.02%) and increased compressive modulus (358.91 +/- 48.05 kPa) after 21 days in culture among all groups. Biochemical analysis showed the most collagen production and highest alkaline phosphatase activity in PEG-HA group, which is consistent with gene expression determined by quantitative PCR. Masson's trichrome staining also showed the most collagen deposition in PEG-HA scaffold. Therefore, HA is more effective comparing to BG for hMSCs osteogenesis in bioprinted bone constructs. Combining with our previous experience in vasculature, cartilage, and muscle bioprinting, this technology demonstrates the capacity for both soft and hard tissue engineering with biomimetic structures. PMID- 25130391 TI - Can a baseline morning cortisol predict outcome of short Synacthen test in an endocrine unit in an outpatient setting. PMID- 25130389 TI - Discoidin domain receptor 2 (DDR2) promotes breast cancer cell metastasis and the mechanism implicates epithelial-mesenchymal transition programme under hypoxia. AB - A wide range of genes involved in breast cancer metastasis have been reported to be related to the microenvironment. We studied the role of discoidin domain receptor 2 (DDR2), a collagen-binding receptor, in breast cancer progression under hypoxic conditions. We showed that DDR2 protein expression closely correlated with the expression of hypoxic marker HIF-1alpha in clinical breast cancer specimens. The in vitro data demonstrated that hypoxia treatment increased the levels of both expression and phosphorylation of DDR2 in human breast cancer cell lines. In vivo, orthotopic breast tumour xenografts with DDR2 knockdown displayed reduced dissemination and significant prevention in pulmonary and lymphatic metastasis; conversely, these processes were significantly facilitated by the enforced expression of the activated form of DDR2. Further mechanism studies indicated that DDR2 plays an indispensable role in a series of hypoxia induced behaviours of breast cancer cells, including migration, invasion, and epithelial-mesenchymal transition (EMT). The transcription factor Snail was found to mediate DDR2-induced down-regulation of the cell-cell adhesion molecule E cadherin. It was also documented that there is a correlation between DDR2 and E cadherin expression with the presence of lymph node metastases in 160 cases of invasive human breast carcinoma. In addition, we provided evidence that DDR2 silencing in breast cancer cells prevents the hypoxia-induced activation of ERK MAPK, suggesting its potential involvement in mediating the effect of DDR2 on hypoxia-induced signalling. Based on the results of this study, we conclude that DDR2 participates in hypoxia-induced breast cancer metastasis through the regulation of cell migration, invasion, and EMT, and thus may serve as an accessible therapeutic target for the treatment of breast cancer. PMID- 25130392 TI - Serum Cytokine Levels in Behcet's Disease. AB - BACKGROUND: The aim of this study is to investigate and compare the serum levels of various cytokines in patients with Behcet's Disease and healthy controls. METHODS: Thirty-five patients with Behcet's disease and 29 age and sex-matched healthy controls were included in the study. The patients were separated into groups with active and inactive disease. Serum IL-2, IL-6, IL-8, IL-10, IL-17A, and IFN-gamma levels were determined using the enzyme-linked immunosorbent assay method. Cytokine levels of the two patient groups and healthy controls were compared using SPSS 15.0. RESULTS: Ten patients with active disease and 25 patients with inactive disease were present. Serum IL-8 levels of active BD patients were higher compared to inactive patients (P = 0.048) and healthy controls (P = 0.02). IL-8 levels were correlated with the duration of symptoms (r = 0.490, P = 0.003) and time passed since diagnosis (r = 0.579, P ? 0.001). CONCLUSION: Behcet's disease involves complex interactions of cells of the immune system, mainly T lymphocytes and neutrophils. Further studies on the cytokine profile in Behcet's disease will aid in elucidation of its pathogenesis. PMID- 25130393 TI - Identification of binding sites for C-terminal pro-gastrin-releasing peptide (GRP)-derived peptides in renal cell carcinoma: a potential target for future therapy. AB - OBJECTIVE: To determine the expression and biology of the neuroendocrine growth factor gastrin-releasing peptide (GRP) and other proGRP-derived peptides in renal cancer. MATERIALS AND METHODS: Receptor binding studies, enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay, were used to quantitate the presence of proGRP-derived peptide receptors and their ligands in renal cancer cell lines and human renal cancers. Biological activity of proGRP peptides was confirmed with proliferation, migration, and extracellular-signal-regulated kinases 1 and 2 (ERK1/2) activation assays in vitro. In vivo, ACHN renal cancer xenografts were treated with proGRP-derived peptides to assess tumour size and necrosis. hypoxia-inducible factor 1alpha (HIF1alpha) and vascular endothelial growth factor (VEGF) expression were investigated with Western blotting and ELISA respectively, to determine the possible contribution of the proGRP peptides to tumour viability. RESULTS: In ACHN cells that expressed both proGRP- and GRP receptors, the expression of proGRP binding sites was 80-fold greater than the GRP-receptor (GRPR). C-terminal proGRP-derived peptides stimulated the activation of ERK1/2, but with a different time course to GRP, consistent with the suggestion that these peptides may have unique cellular functions. Both GRP and proGRP47-68 stimulated proliferation and migration of ACHN cells in vitro, but only GRP reduced the extent of tumour necrosis in ACHN xenografts. GRP, but not proGRP47-68, was able to induce HIF1alpha and VEGF expression in ACHN cells. This may account in part for the reduction in necrosis after GRP treatment. C-terminal proGRP-derived peptides were present in all three renal cancer cell lines and a panel of human renal cancers, but mature amidated GRP was absent. CONCLUSION: C terminal proGRP peptides are more abundant in renal cancers and their cell lines than the more extensively studied amidated peptide, GRP. These results suggest that C-terminal proGRP-derived peptides may be a better target for novel renal cancer treatments. PMID- 25130394 TI - Histone H1.5, a novel prostatic cancer marker: an immunohistochemical study. AB - Histone H1.5 (HH1.5) is a somatic subtype of the histone H1 family of linker proteins that are located in the nucleus and play a role in stabilizing higher order chromatin structure, gene expression, DNA repair, and cell proliferation. Recently, differential immunohistochemical expression of HH1.5 has been found in various neuroendocrine neoplasms. This study aimed to investigate the immunohistochemical expression of HH1.5 in prostatic adenocarcinomas. Sixty-three prostate needle core biopsies, 9 radical prostatectomy specimens, and 3 metastatic prostate cancer cases were evaluated. HH1.5 immunohistochemistry revealed strong nuclear reactivity in 68 (93%) of 73 cases of prostate adenocarcinomas, compared to only 7 (9%) of 75 cases of benign prostatic glands (P <= .0001). In all positive benign prostate epithelium, HH1.5 was limited to focal and weak reactivity. Similarly, all 23 foci of high-grade prostatic intraepithelial neoplasia exhibited focal staining, with the vast majority having only weak nuclear reactivity. Increased HH1.5 reactivity was observed in Gleason patterns 4 and 5 as compared to Gleason pattern 3, 72% and 56%, respectively (P <= .02). All 3 metastatic prostate cancer cases showed strong nuclear reactivity. HH1.5 may be a useful diagnostic tool in evaluating prostatic biopsies, particularly with small foci of cancer. Further studies are needed to support these findings and investigate the possible prognostic significance of HH1.5 in prostatic adenocarcinomas. PMID- 25130395 TI - Protein expression of the chemokine receptor CXCR4 and its ligand CXCL12 in primary cutaneous melanoma--biomarkers of potential utility? AB - Dysregulation of the CXCR4/CXCL12 axis, relevant in melanoma progression, activates cell cycle progression and migration via stimulation of the MAPK pathway. We sought to ascertain the cooperativity of the CXCR4/CXCL12 axis with established prognosticators and BRAF status in melanoma. Samples (n = 107) of primary cutaneous melanoma were assessed for protein expression of CXCR4 and CXCL12, and molecular analyses were performed to ascertain BRAF status. Univariate analyses of CXCR4 protein showed that the proportion of CXCR4 positives was greater in melanomas with absence of mitoses (P < .0001), absence of ulceration (P = .0008), and absence of regression (P = .02). Patients presenting at shallower stages (American Joint Committee on Cancer [AJCC] 1-2) exhibited a larger proportion of CXCR4 positives (76.9%, P < .0001 and 69.0%, P = .008), whereas those at deeper stages (AJCC 3-4) exhibited a larger proportion of negatives (75.0%, P = .004 and 66.7%, P = .22). In a multivariate analysis, lower odds of CXCR4 protein expression were associated with AJCC stage 3 (odds ratio [OR]=0.16, P = .01), AJCC stage 4 (OR=0.17, P = .04), and mitoses (OR=0.21, P = .01). Univariate analyses of CXCL12 protein showed that the proportion of CXCL12 negatives was significantly smaller in melanomas with depth of at least 1 mm, absence of ulceration, and absence of vascular invasion (P < .0001 for all). CXCR4 and CXCL12 appear to be biomarkers associated with established prognosticators of good and poor clinical outcome, respectively, in primary cutaneous melanoma. A BRAF mutation does not appear to be associated with CXCR4/CXCL12 axis upregulation in primary cutaneous melanoma. PMID- 25130396 TI - Multiple metastases from histologically benign intraarticular diffuse-type tenosynovial giant cell tumor: a case report. AB - Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a relatively rare mesenchymal tumor. It is a locally aggressive but virtually nonmetastasizing neoplasm and thus regarded as benign. Only a few D-TGCTs with benign histology have been reported to metastasize. We report an extremely rare case of benign D TGCT in which multiple metastases developed 9 years after surgery for the primary tumor. The present case suggests that conventional D-TGCT has the potential to form distant metastases, albeit exceptionally rarely, and that this probable implantation phenomenon can be managed conservatively. PMID- 25130397 TI - Recent progress in analytical capillary isotachophoresis. AB - This paper brings a survey of papers on analytical capillary ITP published since 2012 until the first quarter of 2014. These papers are ranged according to their nature, the techniques used, and the instrumentation employed. The sequence of the related chapter titles is as follows: Theory and simulations, techniques and instrumentation, single-column and column-switching applications of ITP, ITP in microfluidic systems, on-line ITP-CZE and transient ITP (tITP) techniques and applications. The review shows the position of analytical capillary ITP among contemporary separation techniques and implies the potential future trends. PMID- 25130398 TI - Nonreproductive role of gonadotropin-releasing hormone in the control of ascidian metamorphosis. AB - BACKGROUND: Gonadotropin-releasing hormones (GnRHs) are neuropeptides that play central roles in the reproduction of vertebrates. In the ascidian Ciona intestinalis, GnRHs and their receptors are expressed in the nervous systems at the larval stage, when animals are not yet capable of reproduction, suggesting that the hormones have non-reproductive roles. RESULTS: We showed that GnRHs in Ciona are involved in the animal's metamorphosis by regulating tail absorption and adult organ growth. Absorption of the larval tail and growth of the adult organs are two major events in the metamorphosis of ascidians. When larvae were treated with GnRHs, they completed tail absorption more frequently than control larvae. cAMP was suggested to be a second messenger for the induction of tail absorption by GnRHs. tGnRH-3 and tGnRH-5 (the "t" indicates "tunicate") inhibited the growth of adult organs by arresting cell cycle progression in parallel with the promotion of tail absorption. CONCLUSIONS: This study provides new insights into the molecular mechanisms of ascidian metamorphosis conducted by non reproductive GnRHs. PMID- 25130399 TI - Mitochondrial complex I activity suppresses inflammation and enhances bone resorption by shifting macrophage-osteoclast polarization. AB - Mitochondrial complex I (CI) deficiency is associated with multiple neurological and metabolic disorders. However, its effect on innate immunity and bone remodeling is unclear. Using deletion of the essential CI subunit Ndufs4 as a model for mitochondrial dysfunction, we report that mitochondria suppress macrophage activation and inflammation while promoting osteoclast differentiation and bone resorption via both cell-autonomous and systemic regulation. Global Ndufs4 deletion causes systemic inflammation and osteopetrosis. Hematopoietic Ndufs4 deletion causes an intrinsic lineage shift from osteoclast to macrophage. Liver Ndufs4 deletion causes a metabolic shift from fatty acid oxidation to glycolysis, accumulating fatty acids and lactate (FA/LAC) in the circulation. FA/LAC further activates Ndufs4(-/-) macrophages via reactive oxygen species induction and diminishes osteoclast lineage commitment in Ndufs4(-/-) progenitors; both inflammation and osteopetrosis in Ndufs4(-/-) mice are attenuated by TLR4/2 deletion. Together, these findings reveal mitochondrial CI as a critical rheostat of innate immunity and skeletal homeostasis. PMID- 25130400 TI - FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss. AB - The mechanism by which pharmacologic administration of the hormone FGF21 increases energy expenditure to cause weight loss in obese animals is unknown. Here we report that FGF21 acts centrally to exert its effects on energy expenditure and body weight in obese mice. Using tissue-specific knockout mice, we show that betaKlotho, the obligate coreceptor for FGF21, is required in the nervous system for these effects. FGF21 stimulates sympathetic nerve activity to brown adipose tissue through a mechanism that depends on the neuropeptide corticotropin-releasing factor. Our findings provide an unexpected mechanistic explanation for the strong pharmacologic effects of FGF21 on energy expenditure and weight loss in obese animals. PMID- 25130402 TI - The structure of the gas bladder of the spotted gar, Lepisosteus oculatus. AB - We report here on the macroscopic, light microscopic, and electron microscopic structure of the gas bladder (GB) of the spotted gar, Lepisosteus oculatus. The GB opens into the pharynx, dorsal to the opening of the oesophagus, through a longitudinal slit bordered by two glottal ridges. Caudal to the ridges, the GB is an elongated sac divided into a central duct and right and left lobes. The lobes are formed by a cranio-caudal sequence of large air spaces that open into the central duct. The structure of the GB is that of a membranous sac supported by a system of septa arising from the walls of a central duct. The septa contain variable amounts of striated and smooth muscle might function to maintain the bladder shape and in providing contractile capabilities. The presence of muscle cells, nerves, and neuroepithelial cells in the wall of the GB strongly suggests that GB function is tightly regulated. The central duct and the apical surface of the thickest septa are covered by mucociliated epithelium. Most of the rest of the inner bladder surface is covered by a respiratory epithelium which contains goblet cells and a single type of pneumocyte. These two cell types produce surfactant. The respiratory barrier contains thick areas with fibrillar material and cell prolongations, and thin areas that only contain basement membrane material between the capillary wall and the respiratory epithelium. Lungs and GBs share many anatomical and histological features. There appears to be no clear criterion for structural distinction between these two types of respiratory organs. PMID- 25130404 TI - Bedside interprofessional rounds: perceptions of benefits and barriers by internal medicine nursing staff, attending physicians, and housestaff physicians. AB - BACKGROUND: Interprofessional collaboration improves the quality of care, but integration into workflow is challenging. Although a shared conceptualization regarding bedside interprofessional rounds may enhance implementation, little work has investigated providers' perceptions of this activity. OBJECTIVE: To evaluate the perceptions of nurses, attending physicians, and housestaff physicians regarding the benefits/barriers to bedside interprofessional rounds. DESIGN AND PARTICIPANTS: Observational, cross-sectional survey of hospital-based medicine nurses, attending physicians, and housestaff physicians. Descriptive, nonparametric Wilcoxon rank sum and nonparametric correlation were used. MAIN MEASURES: Bedside interprofessional rounds were defined as "encounters including 2 physicians plus a nurse or other care provider discussing the case at the patient's bedside." Eighteen items related to "benefits" and 21 items related to "barriers" associated with bedside interprofessional rounds. RESULTS: Of 171 surveys sent, 149 were completed (87%). Highest-ranked benefits were related to communication/coordination, including "improves communication between nurses physicians;" lowest-ranked benefits were related to efficiency, process, and outcomes, including "decreases length-of-stay" and "improves timeliness of consultations." Nurses reported most favorable ratings for all items (P < 0.05). Rank order for 3 provider groups showed high correlation (r = 0.92, P < 0.001). Highest-ranked barriers were related to time, including "nursing staff have limited time;" lowest-ranked barriers were related to provider- and patient related factors, including "patient lack of comfort." Rank order of barriers among all groups showed moderate correlation (r = 0.62-0.82). CONCLUSIONS: Although nurses perceived greater benefit for bedside interprofessional rounds than physicians, all providers perceived coordination/teamwork benefits higher than outcomes. To the extent the results are generalizable, these findings lay the foundation for facilitating meaningful patient-centered interprofessional collaboration. PMID- 25130403 TI - Malignant peripheral nerve sheath tumors (MPNST): a SEER analysis of incidence across the age spectrum and therapeutic interventions in the pediatric population. AB - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are very rare in the general population and challenging to treat. A paucity of data exists regarding the incidence of MPNST across all age groups and treatment outcomes in the pediatric population. We aimed to characterize both using the Survival, Epidemiology, and End Results (SEER) database. PROCEDURE: The SEER-18 database with information on the United States population from 1973 to 2009 was queried for cases of MPNST. For incidence data, 1,182 cases were found among the general population. Of those, 165 cases were in individuals aged 0-19. After exclusions, 139 cases from the SEER-18 database met study criteria for outcomes analysis. For each patient, variables including gender, age, race, stage (localized, regional, or distant), surgical treatment, and radiotherapy were obtained. RESULTS: The overall incidence of MPNST was 1.46 per million person-years, with increased incidence among the elderly. In the pediatric population, the incidence was 0.56 per million person-years, and was higher among post-pubertal children aged 10-19. Median overall survival in the pediatric population was 30 months, with only localized disease and treatment with surgery being positive prognostic factors on multivariate analysis. CONCLUSIONS: MPNST is a rare disease and, among children, is most frequent seen in adolescents. Surgery is crucial as first-line treatment for MPNST, especially if the tumor is localized at diagnosis. In patients with non-localized MPNST, the disease remains extremely difficult to manage, and both surgery and radiotherapy are interventions that should be considered. PMID- 25130405 TI - Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease. AB - OBJECTIVES: To evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease. ANIMALS: Seventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease. METHODS: Prospective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed. RESULTS: The hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6-12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6-12.6 months), compared to 54 months (46 - infinity) for dogs with concentrations <= 1000 pmol/l (p < 0.001). Due to intra- and inter individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 MUmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (>= 3/6). CONCLUSIONS: The risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months. PMID- 25130406 TI - Atrial septal pacing in small dogs: a pilot study. AB - OBJECTIVE: To determine the feasibility of atrial septal pacing via a delivery catheter-guided small non-retracting helix pacing lead. ANIMALS: Six healthy beagles (8.3-12.9 kg). METHODS: Using single plane fluoroscopic guidance, Medtronic((r)) 3830 SelectSecure leads were connected to the atrial septum via Medtronic(r) Attain Select(r) II standard 90 Left Heart delivery catheter. Pacing threshold and lead impedance were measured at implantation. The Wenckebach point was tested via atrial pacing up to 220 paced pulses per minute (ppm). Thoracic radiographs were performed following implantation to identify the lead position, and repeated at 24 h, 1 month, and 3 months post-operatively. RESULTS: Macro-lead dislodgement occurred in two dogs at 24 h and in three dogs at one-month post implantation. Lead impedance, measured at the time of implantation, ranged from 583 to 1421 Omega. The Wenckebach point was >220 ppm in four of the six dogs. The remaining two dogs had Wenckebach points of 120 and 190 ppm. CONCLUSIONS: This pilot study suggests the selected implantation technique and lead system were inadequate for secure placement in the atrial septum of these dogs. The possible reasons for inadequate stability include unsuitable lead design for this location, inadequate lead slack at the time of implantation and inadequate seating of the lead as evidenced by low impedance at the time of implantation. Other implantation techniques and/or pacing leads should be investigated to determine the optimal way of pacing the atria in small breed dogs that are prone to sinus node dysfunction. PMID- 25130401 TI - A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia. AB - Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL. PMID- 25130408 TI - A quantitative geometric mechanics lens model: insights into the mechanisms of accommodation and presbyopia. AB - This study expands on a geometric model of ocular accommodation (Reilly and Ravi, Vision Res. 50:330-336; 2010) by relaxing assumptions regarding lens symmetry about the equator. A method for predicting stretching force was derived. Two models were then developed: Model 1 held the equatorial geometry constant at all stages of accommodation, while Model 2 allowed localized deformation at the equator. Both models were compared to recent data for axial thickness, anterior and posterior radii of curvature, surface area, cross-sectional area, volume, and stretching force for the 29-year-old lens. Age-related changes in accommodation were also simulated. Model 1 gave predictions which agreed with the Helmholtz theory of accommodation, while Model 2's predictions agreed with the Schachar mechanism of accommodation. Trends predicted by Model 1 agreed with all available experimental data, while Model 2 disagreed with recent surface area measurements. Further analysis indicated that Model 1 was fundamentally more efficient in that it required less force per diopter change in optical power than Model 2. Model 1 more accurately predicted age-related changes in accommodation amplitude. This implies that the zero-force (fully accommodated) state geometry changes with age due to a shifting balance in residual stresses between the lens and capsule. PMID- 25130407 TI - How shape from contours affects shape from shading. AB - The spatial pattern of reflected light carries detailed but ambiguous information about 3D shapes of illuminated objects. A little studied factor that affects the perceived 3D relief of 2D shaded figures is the shape of their contours. An experiment is reported in which 102 subjects matched twelve contoured grating displays (horizontal three-cycle gratings with variously shaped top and bottom contours) with perspective line drawings of different 3D shapes, and also judged their depth extent and direction of illumination. The results showed that contour shapes can have surprisingly strong and salient effects on perceived relief. For each display there was a dominant matching drawing, chosen by the largest percentage of subjects, which varied from 95% to 26% across the set of displays. The luminance distribution of contoured gratings is essentially 1D, so that, compared to the general 2D case, their mathematical analysis is considerably simplified, and shape can in certain cases be recovered from shading in analytical form, yielding a three-parameter family of solutions. An analysis of subject responses showed that most reported reliefs had shapes which were closely related to members of the solution family. Furthermore, the particular perceived shapes of contoured gratings could with some success be predicted from the shapes of their contours, based on a simple shape-from-contours rule. However, the data also indicated the presence of a convexity tendency, independent from contour shape. PMID- 25130409 TI - Efficiency of electronically monitored amblyopia treatment between 5 and 16 years of age: new insight into declining susceptibility of the visual system. AB - The notion of a limited, early period of plasticity of the visual system has been challenged by more recent research demonstrating functional enhancement even into adulthood. In amblyopia ("lazy eye") it is still unclear to what extent the reduced effect of treatment after early childhood is due to declining plasticity or lower compliance with prescribed patching. The aim of this study was to determine the dose-response relationship and treatment efficiency from acuity gain and electronically recorded patching dose rates, and to infer from these parameters on a facet of age dependence of functional plasticity related to occlusion for amblyopia. The Occlusion Dose Monitor was used to record occlusion in 27 participants with previously untreated strabismic and/or anisometropic amblyopia aged between 5.4 and 15.8 (mean 9.2) years during 4months of conventional treatment. Group data showed improvement of acuity throughout the age span, but significantly more in patients younger than 7years despite comparable patching dosages. Treatment efficiency declined with age, with the most pronounced effects before the age of 7years. Thus, electronic recording allowed this first quantitative insight into occlusion treatment spanning the age range from within to beyond the conventional age for patching. Though demonstrating improvement in over 7year old patients, it confirmed the importance of early detection and treatment of amblyopia. Treatment efficiency is presented as a tool extending insight into age-dependent functional plasticity of the visual system, and providing a basis for comparisons of effects of patching vs. emerging alternative treatment approaches for amblyopia. PMID- 25130410 TI - Bias corrected double judgment accuracy during spatial attention cueing: unmasked stimuli with non-predictive and semi-predictive cues. AB - The present experiments indicate that in a 7-AFC double judgment accuracy task with unmasked stimuli, cue location response bias can be quantified and removed, revealing unbiased improvements in response accuracy for valid cues compared to invalid cues. By testing for cueing effects over a range of contrast levels with unmasked stimuli, changes in the psychometric function were examined and provide insight into the mechanisms of involuntary attention which might account for the observed cueing effects. Cue validity was varied between two separate experiments showing that non-predictive (14.3%) and moderately-predictive cues (50%) equally facilitate stimulus identification and localization during transient involuntary attention capture. Observers had improved accuracy at identifying both the location and the feature identity of target letters throughout a range of contrast levels, without any dependence on backward masking. There was a leftward shift of the psychometric function threshold with valid cued data and no slope reduction suggesting that any additive hypothesis based on spatial uncertainty reduction or perceptual enhancement is not a sufficient explanation for the observed cueing effects. The interdependence of the perceptual processes of stimulus discrimination and localization were also investigated by analyzing response contingencies, showing that observers were equally skilled at making identification and localization accuracy judgments with unmasked stimuli. PMID- 25130411 TI - Identification of phenanthrene derivatives in Aerides rosea (Orchidaceae) using the combined systems HPLC-ESI-HRMS/MS and HPLC-DAD-MS-SPE-UV-NMR. AB - INTRODUCTION: In our continued efforts to contribute to the general knowledge on the chemical diversity of orchids, we have decided to focus our investigations on the Aeridinae subtribe. Following our previous phytochemical study of Vanda coerulea, which has led to the identification of phenanthrene derivatives, a closely related species, Aerides rosea Lodd. ex Lindl. & Paxton, was chosen for investigation. OBJECTIVE: To identify new secondary metabolites, and to avoid isolation of those already known, by means of the combined systems HPLC-DAD(diode array detector) with high-resolution tandem mass spectrometry (HRMS/MS) and HPLC DAD-MS-SPE(solid-phase extraction)-UV-NMR. METHODS: A dereplication strategy was developed using a HPLC-DAD-HRMS/MS targeted method and applied to fractions from A. rosea stem extract. Characterisation of unknown minor compounds was then performed using the combined HPLC-DAD-MS-SPE-UV-NMR system. RESULTS: The dereplication method allowed the characterisation of four compounds (gigantol, imbricatin, methoxycoelonin and coelonin), previously isolated from Vanda coerulea stem extract. The analyses of two fractions permitted the identification of five additional minor constituents including one phenanthropyran, two phenanthrene and two dihydrophenanthrene derivatives. The full set of NMR data of each compound was obtained from microgram quantities. CONCLUSION: Nine secondary metabolites were characterised in A. rosea stems, utilising HPLC systems combined with high-resolution analytical systems. Two of them are newly described phenanthrene derivatives: aerosanthrene (5-methoxyphenanthrene-2,3,7-triol) and aerosin (3-methoxy-9,10-dihydro-2,5,7-phenanthrenetriol). PMID- 25130412 TI - Neoadjuvant chemotherapy followed by surgery in very locally advanced technically unresectable oral cavity cancers. AB - BACKGROUND: The median survival of technically unresectable oral-cavity cancers (T4a and T4b) with non surgical therapy is 2-12 months. We hypothesized that neoadjuvant chemotherapy (NACT) could reduce the tumour size and result in successful resection and ultimately improved outcomes. We present a retrospective analysis of consecutive patients who received NACT at our centre between January 2008 and August 2012. PATIENTS AND METHODS: All patients with technically unresectable oral cancers were assessed in a multidisciplinary clinic and received 2 cycles of NACT. After 2 cycles, patients were reassessed and planned for either surgery with subsequent CTRT or nonsurgical therapy including CT-RT, RT or palliation. SPSS version 16 was used for analysis of locoregional control and overall survival (OS). Univariate and multivariate analysis was done for factors affecting the OS. RESULTS: 721 patients with stage IV oral-cavity cancer received NACT. 310 patients (43%) had sufficient reduction in tumour size and underwent surgical resection. Of the remaining patients, 167 received chemoradiation, 3 radical radiation and 241 palliative treatment alone The locoregional control rate at 24 months was 20.6% for the overall cohort, 32% in patients undergoing surgery and 15% in patients undergoing non surgical treatment (p=0.0001). The median estimated OS in patients undergoing surgery was 19.6 months (95% CI, 9.59-25.21 months) and 8.16 months (95%, CI 7.57-8.76) in patients treated with non surgical treatment (p=0.0001). CONCLUSION: In our analysis, NACT led to successful resection and improved overall survival in a significant proportion of technically unresectable oral-cancer patients. PMID- 25130413 TI - Oral health, dental care and mouthwash associated with upper aerodigestive tract cancer risk in Europe: the ARCAGE study. PMID- 25130414 TI - Correlation between chronic inflammation and oral squamous cell carcinoma (OSCC). PMID- 25130415 TI - Labeled protein recognition at a membrane bilayer interface by embedded synthetic receptors. AB - Self-folding deep cavitands embedded in a supported lipid bilayer are capable of recognizing suitably labeled proteins at the bilayer interface. The addition of a choline derived binding "handle" to a number of different proteins allows their selective noncovalent recognition, with association constants on the order of 10(5) M(-1). The proteins are displayed at the water:bilayer interface, and a single binding handle allows recognition of the large, charged protein by a small molecule synthetic receptor via complementary shape and charge interactions. PMID- 25130417 TI - Polysomnography: assessment of decannulation readiness in chronic upper airway obstruction. AB - OBJECTIVES/HYPOTHESIS: To evaluate the clinical value of polysomnography in patients with a tracheotomy due to chronic upper airway obstruction prior to attempting decannulation. STUDY DESIGN: Retrospective chart review. METHODS: Subjects with chronic upper airway obstruction were identified using a clinical database between 2000 and 2014. All subjects had a tracheotomy, were assessed by the senior author in a tertiary care academic center, and underwent polysomnography prior to attempting decannulation. Patients were excluded if they did not undergo polysomnography or had severe obstructive sleep apnea as the primary indication for tracheotomy. RESULTS: Fifteen patients were identified. The majority (87.5%) of patients were successfully decannulated after their first polysomnography showed acceptable results when carried out with the tracheotomy occluded. Obstructive sleep apnea was identified in four of the nine patients who tolerated overnight tracheotomy occlusion, and continuous positive airway pressure (CPAP) was initiated. An additional four of the remaining six patients were decannulated after subsequent polysomnography demonstrated improvement with CPAP, and two required an additional airway procedure. CONCLUSIONS: Chronic upper airway obstruction requiring tracheotomy can be challenging to treat and successfully decannulate. Indirect laryngoscopy is essential to evaluate the anatomy of the larynx; however, it cannot assess potential increased obstruction during sleep. The study indicates that polysomnography can assist with the evaluation of decannulation readiness in patients with chronic upper airway obstruction as an adjunct measure in addition to imaging and laryngoscopy. LEVEL OF EVIDENCE: 4. PMID- 25130418 TI - Ultrathin core-sheath fibers for liposome stabilization. AB - Ultrathin core-sheath fibers with small unilamellar vesicles (SUVs) in the core were prepared by coaxial electrospinning. SUVs/sodium hyaluranate (HA-Na)/water and polyvinylpyrrolidone (PVP)/ethanol solutions were used as core and sheath fluid in electrospinning, respectively. The ultrathin fibers were characterized by scanning and transmission electron microscopy (SEM and TEM) and laser scanning confocal microscopy (LSCM). The SUVs were successfully encapsulated in the core HA-Na matrix of the ultrathin fibers and are in the elliptic shape. The SUVs encapsulated in the core matrix of the ultrathin fibers have an excellent stability. The SUVs embedded in the ultrathin fibers are stable. When the ultrathin fibers were re-dissolved in water after one-month storage at room temperature, the rehydrated SUVs have the similar size and size distribution as the as-prepared SUVs. The liposome-loaded ultrathin fiber mats have the promising applications in wound healing materials. PMID- 25130416 TI - Modeling the effects of sensory reinforcers on behavioral persistence with alternative reinforcement. AB - Problem behavior often has sensory consequences that cannot be separated from the target response, even if external, social reinforcers are removed during treatment. Because sensory reinforcers that accompany socially mediated problem behavior may contribute to persistence and relapse, research must develop analog sensory reinforcers that can be experimentally manipulated. In this research, we devised analogs to sensory reinforcers in order to control for their presence and determine how sensory reinforcers may impact treatment efficacy. Experiments 1 and 2 compared the efficacy of differential reinforcement of alternative behavior (DRA) versus noncontingent reinforcement (NCR) with and without analog sensory reinforcers in a multiple schedule. Experiment 1 measured the persistence of key pecking in pigeons, whereas Experiment 2 measured the persistence of touchscreen responses in children with intellectual and developmental disabilities. Across both experiments, the presence of analog sensory reinforcers increased the levels, persistence, and variability of responding relative to when analog sensory reinforcers were absent. Also in both experiments, target responding was less persistent under conditions of DRA compared to NCR regardless of the presence or absence of analog sensory reinforcers. PMID- 25130419 TI - Delphinid systematics and biogeography with a focus on the current genus Lagenorhynchus: multiple pathways for antitropical and trans-oceanic radiation. AB - The six species currently classified within the genus Lagenorhynchus exhibit a pattern of antitropical distribution common among marine taxa. In spite of their morphological similarities they are now considered an artificial grouping, and include both recent and the oldest representatives of the Delphinidae radiation. They are, therefore, a good model for studying questions about the evolutionary processes that have driven dolphin speciation, dispersion and distribution. Here we used two different approaches. First we constructed a multigenic phylogeny with a minimum amount of missing data (based on 9 genes, 11,030bp, using the 6 species of the genus and their closest relatives) to infer their relationships. Second, we built a supermatrix phylogeny (based on 33 species and 27 genes) to test the effect of taxon sampling on the phylogeny of the genus, to provide inference on biogeographic history, and provide inference on the main events shaping the dispersion and radiation of delphinids. Our analyses suggested an early evolutionary history of marine dolphins in the North Atlantic Ocean and revealed multiple pathways of migration and radiation, probably guided by paleoceanographic changes during the Miocene and Pliocene. L. acutus and L. albirostris likely shared a common ancestor that arose in the North Atlantic around the Middle Miocene, predating the radiation of subfamilies Delphininae, Globicephalinae and Lissodelphininae. PMID- 25130420 TI - Highly sensitive assay for acetylcholinesterase activity and inhibition based on a specifically reactive photonic nanostructure. AB - Assays for acetylcholinesterase (AChE) with high sensitivity and high selectivity as well as facile manipulation have been urgently required in various fields. In this work, a reaction-based photonic strategy was developed for the efficient assay of AChE activity and inhibition based on the synergetic combination of the specific thiol-maleimide addition reaction with photonic porous structure. It was found that various applications including detection of AChE activity, measurement of the related enzymatic kinetics, and screening of inhibitors could be efficiently implemented using such strategy. Remarkably, the unique photonic nanostructure endows the constructed sensing platform with high sensitivity with a limit of detection (LOD) of 5 mU/mL for AChE activity, high selectivity, and self-reporting signaling. Moreover, the label-free solid film-based sensing approach described here has advantages of facile manipulation and bare-eye readout, compared with conventional liquid-phase methods, exhibiting promising potential in practical application for the AChE assay. PMID- 25130422 TI - A dogma-breaking concept: glutamate oxidation in astrocytes is the source of lactate during aerobic glycolysis in resting subjects. PMID- 25130421 TI - The longitudinal effects of physical activity and dietary calcium on bone mass accrual across stages of pubertal development. AB - Childhood and adolescence are critical periods of bone mineral content (BMC) accrual that may have long-term consequences for osteoporosis in adulthood. Adequate dietary calcium intake and weight-bearing physical activity are important for maximizing BMC accrual. However, the relative effects of physical activity and dietary calcium on BMC accrual throughout the continuum of pubertal development in childhood remains unclear. The purpose of this study was to determine the effects of self-reported dietary calcium intake and weight-bearing physical activity on bone mass accrual across the five stages of pubertal development in a large, diverse cohort of US children and adolescents. The Bone Mineral Density in Childhood study was a mixed longitudinal study with 7393 observations on 1743 subjects. Annually, we measured BMC by dual-energy X-ray absorptiometry (DXA), physical activity and calcium intake by questionnaire, and pubertal development (Tanner stage) by examination for up to 7 years. Mixed effects regression models were used to assess physical activity and calcium intake effects on BMC accrual at each Tanner stage. We found that self-reported weight-bearing physical activity contributed to significantly greater BMC accrual in both sexes and racial subgroups (black and nonblack). In nonblack males, the magnitude of the activity effect on total body BMC accrual varied among Tanner stages after adjustment for calcium intake; the greatest difference between high- and low-activity boys was in Tanner stage 3. Calcium intake had a significant effect on bone accrual only in nonblack girls. This effect was not significantly different among Tanner stages. Our findings do not support differential effects of physical activity or calcium intake on bone mass accrual according to maturational stage. The study demonstrated significant longitudinal effects of weight-bearing physical activity on bone mass accrual through all stages of pubertal development. PMID- 25130424 TI - Residual left atrial mass after myxoma resection. PMID- 25130423 TI - Response: Does perioperative dexmedetomidine improve mortality after coronary artery bypass surgery? PMID- 25130425 TI - Dynamism of the mitral annulus: a spatial and temporal analysis. AB - OBJECTIVE: In this study, the authors sought to investigate the extent and timing of changes in mitral annular area during the cardiac cycle. Particularly, the authors assessed whether these changes were limited to the posterior part of the annulus or were more global in nature. DESIGN: Prospective, observational study SETTING: Tertiary care university hospital PARTICIPANTS: Twenty three patients undergoing non-valvular cardiac surgery and 3 patients undergoing vascular procedures. INTERVENTIONS: Intraoperative 3-dimensional transesophageal echocardiographic data obtained from patients with normal mitral valves undergoing non-valvular cardiac surgery were analyzed geometrically. Annular areas and diameters were measured during various stages of the cardiac cycle. Intertrigonal distance also was measured using 3D data. MEASUREMENTS AND MAIN RESULTS: Both anterior and posterior portions of the mitral annulus demonstrated dynamism throughout the cardiac cycle. The expansion phase ranged from mid systole to early-diastole, whereas mid-diastole to early-systole was characterized by an annular contraction phase. Area changes were contributed equally by anterior and posterior parts of the annulus. Annular dimensions increased in accordance with mitral annular area (p<0.05). Echocardiographically identified intertrigonal distance showed the least delta change. CONCLUSIONS: Both the anterior and posterior parts of the annulus contribute to changes in mitral annular area, which undergoes discrete expansion and contraction phases that extend into both systole and diastole. Compared to other annular dimensions, the echocardiographically-identified intertrigonal distance does not change significantly during the cardiac cycle. PMID- 25130426 TI - Does perioperative dexmedetomidine improve mortality after coronary artery bypass surgery? PMID- 25130427 TI - Genetic ablation of solute carrier family 7a3a leads to hepatic steatosis in zebrafish during fasting. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder caused by abnormal lipid metabolisms, such as reduced hepatic fatty acid oxidation (FAO), but intracellular control of FAO under physio- and pathological conditions remains largely undefined. Here, we demonstrate that deprivation of Slc7a3a leads to hepatic steatosis in fasted zebrafish as a result of defects in arginine-dependent nitric oxide (NO) synthesis. Fast-induced hepatic steatosis in slc7a3a-null mutants can be rescued by treatments with NO donor, cyclic guanosine monophosphate analog, adenosine-monophosphate-activated protein kinase (AMPK) activator, or peroxisome proliferator-activated receptor alpha (PPAR-alpha) agonist. In contrast, inhibitors of NO synthases, AMPK, or soluble guanylate cyclase and liver-specifically expressed dominant negatives of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha and PPAR-alpha are sufficient to induce hepatic steatosis in fasted wild-type larvae. Moreover, knockdown of Slc7a3 in mice or SLC7A3 in human liver cells impaired AMPK-PPAR alpha signaling and resulted in lipid accumulation under fasting or glucose starvation, respectively. CONCLUSION: These findings have revealed a NO-AMPK-PPAR alpha-signaling pathway that is crucial for the control of hepatic FAO in vertebrates. PMID- 25130428 TI - Pressure pain thresholds fluctuate with, but do not usefully predict, the clinical course of painful temporomandibular disorder. AB - Central sensitization elicits pain hypersensitivity and is thought to be causally implicated in painful temporomandibular disorder (TMD). This causal inference is based on cross-sectional evidence that people with TMD have greater sensitivity than controls to noxious stimuli. We tested this inference in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study of 3258 adults with no lifetime history of TMD when enrolled (visit 1). During 5 years of follow-up, 1 group labeled "persistent TMD cases" (n=72) developed first onset TMD by visit 2 that persisted ? 6 months until visit 3. Another group labeled "transient TMD cases" (n=75) developed first-onset TMD at visit 2, which resolved by visit 3. Randomly sampled "controls" (n=126) remained TMD-free throughout all 3 visits. At each visit, pressure pain thresholds (PPTs) were measured by algometry at 10 cranial and bodily sites. In persistent TMD case patients, mean PPTs reduced 43 kPa (P<.0001) between visits 1 and 2 and thereafter did not change significantly. In transient TMD case patients, mean PPTs reduced 41 kPa (P<.001) between visits 1 and 2, and then increased 20 kPa (P<.001) by visit 3. These patterns were similar after excluding cranial sites symptomatic for TMD. Importantly, visit 1 PPTs had no clinically useful prognostic value in predicting first-onset TMD (odds ratio [OR]=1.07, P=.15). Among first-onset case patients, visit 2 PPTs were modest predictors of persistent TMD (OR=1.36, P=.002). In this longitudinal study, PPTs reduced when TMD developed then rebounded when TMD resolved. However, premorbid PPTs poorly predicted TMD incidence, countering the hypothesis that PPTs signify mechanisms causing first-onset TMD. PMID- 25130430 TI - Cytokines and disability in interferon-beta-1b treated and untreated women with multiple sclerosis. AB - BACKGROUND AND AIMS: T-helper (Th) cells involved in the pathogenesis of multiple sclerosis (MS) represent a functionally heterogeneous population defined by their cytokine secretion profile. The effects of immunotherapeutic drugs on the cytokine network are still not fully clarified. This study aimed to investigate serum levels of IFN-gamma, TNF-alpha, IL-4, IL-10 in interferon-beta-1b-treated and untreated women with relapsing-remitting MS (RRMS) in comparison with healthy controls and the relationship between cytokine concentrations and the degree of disability. METHODS: The study included 35 women with RRMS and 35 age-matched healthy controls. The patients were divided in two groups: Group A-without disease modifying treatment; Group B-treated with interferon-beta-1b. Degree of disability was assessed by the Expanded Disability Status Scale (EDSS). Serum cytokine concentrations were measured by ELISA during relapse and remission. RESULTS: Group A showed higher IFN-gamma in remission (p = 0.0239) than the controls; Group B had lower IFN-gamma during relapse (p = 0.0226) than controls. EDSS in relapse correlated with the levels of IL-10 for Group A (p = 0.015) and with the concentration of IFN-gamma for Group B (p = 0.039). Nontreated patients showed higher EDSS in relapse compared to the interferon-beta-1b-treated group (p = 0.005). CONCLUSIONS: We found an imbalance in the patients' cytokine profile, which may be seen as supportive of the hypothesis that demyelination in the central nervous system is mediated by Th1 lymphocytes. IFN-gamma is probably one of the important indicators for intensity of the immune reaction and shows promise as a potential biomarker for the therapeutic effect of interferon-beta 1b. The role of IL-10 in the autoimmune process needs further investigation. PMID- 25130431 TI - The effects of Gremlin1 on human umbilical cord blood hematopoietic progenitors. AB - Bone morphogenetic proteins (BMPs) support malignant hematopoiesis in CML. Conversely, the multi-functional BMP antagonist Gremlin1 supports self-renewing cancer stem cells of other malignancies. Inhibition of BMP signaling in CML, or of Gremlin1 in solid tumors, may therefore have therapeutic potential. However, since BMPs regulate hematopoietic stem cell (HSC) decisions in the stem cell niche, it is necessary to determine how Gremlin1 influences normal HSC. We examined the effects of Gremlin1 on long-term culture-initiating cells (LTC-IC) and transplantable hematopoietic stem cells (SCID-repopulating cells: SRC) in human umbilical cord blood. Gremlin1 inhibited BMP signaling, downregulated BMP-6 and cyclin E2 expression and upregulated hairy and enhancer of split-1 (HES-1; a Notch transcriptional target) and Hedgehog interacting protein-1 (HHIP-1; an inhibitor of Hedgehog signaling). The functional effects of Gremlin1 on SRC, i.e. skewing of their myelopoietic:lymphopoietic potential towards B lymphopoiesis without affecting long-term engraftment potential, were entirely consistent with changes in gene expression induced by Gremlin1. Since both BMPs and Gremlin1 are secreted by osteoblasts in vivo, our studies provide potential insights into the molecular regulation of hematopoiesis in the stem cell niche. These results also suggest that Gremlin1 (and possibly its mimetics that may be developed for therapeutic use) may not adversely affect normal human hematopoietic stem cell survival, though they may reduce their myelopoietic potential. PMID- 25130429 TI - Natural antioxidants exhibit chemopreventive characteristics through the regulation of CNC b-Zip transcription factors in estrogen-induced breast carcinogenesis. AB - The objective of the present study was to characterize the role of resveratrol (Res) and vitamin C (VC) in prevention of estrogen-induced breast cancer through regulation of cap "n"collar (CNC) b-zip transcription factors. Human breast epithelial cell line MCF-10A was treated with 17beta-estradiol (E2) and VC or Res with or without E2. mRNA and protein expression levels of CNC b-zip transcription factors nuclear factor erythroid 2-related factor 1 (Nrf1), nuclear factor erythroid 2 related factor 2 (Nrf2), nuclear factor erythroid 2 related factor 3 (Nrf3), and Nrf2-regulated antioxidant enzymes superoxide dismutase 3 (SOD3) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were quantified. The treatment with E2 suppressed, whereas VC and Res prevented E2-mediated decrease in the expression levels of SOD3, NQO1, Nrf2 mRNA, and protein in MCF-10A cells. The treatment with E2, Res, or VC significantly increased mRNA and protein expression levels of Nrf1. 17beta-Estradiol treatment significantly increased but VC or Res decreased Nrf3 mRNA and protein expression levels. Our studies demonstrate that estrogen induced breast cancer might be prevented through upregulation of antioxidant enzymes via Nrf-dependent pathways. PMID- 25130432 TI - Cellular proteolytic modification of tumor-suppressor CYLD is critical for the initiation of human T-cell acute lymphoblastic leukemia. AB - There exists a general recognition of the fact that post translational modification of CYLD protein through proteolytic cleavage by MALT-1 results in sustained cellular NF-kB activity which is conspicuously found to be associated with cancer in general and hematological malignancies in particular. The present study was directed to understand the contribution of MALT-1 and deubiquitinase CYLD to the initiation of T-cell acute lymphoblastic leukemia (T-ALL). Such a study revealed for the first time that the 35kDa CYLD cleaved factor generated by MALT-1 mediated proteolytic cleavage was conspicuously present in human T- ALL subjects of pediatric age group. Further, over-expression of this 35kDa CYLD factor within normal human peripheral blood mononuclear cells had the inherent capacity to program the genome of these cells resulting in T-cell lineage ALL. Based upon these results, we propose that MALT1 inhibitors may be of crucial importance in the treatment of T-ALL subjects of pediatric age group. PMID- 25130433 TI - IFN-gamma CA microsatellite polymorphism is associated with susceptibility to respiratory syncytial virus Infection and severity. AB - AIM: IFN-gamma, an essential cytokine in the viral cell-mediated immune response, has been associated with the pathogenesis of respiratory syncytial virus (RSV) bronchiolitis and to the severity of the infection. The aim of this study was to investigate whether IFN-gamma CA microsatellite (rs3138557) polymorphism was associated with susceptibility to RSV in Chinese Han children and with the severity of the infection. METHODS: The IFN-gamma CA microsatellite was tested in 218 RSV bronchiolitis inpatients and 303 healthy controls, and the severity of the RSV bronchiolitis was evaluated using a standardised respiratory scoring system. RESULTS: The frequencies of CA12+/CA12+, CA12+/CA12- and CA12-/CA12- in the 218 RSV bronchiolitis patients and 303 controls were approximately 11% versus 19%, 55% versus 53% and 34% versus 28%, respectively. The gene polymorphism of IFN-gamma CA repeats between the two groups was statistically different. The clinical respiratory scores of RSV bronchiolitis cases with CA12+/CA12+ and CA12+/CA12- were 2.84 +/- 0.40 (SD) and 2.95 +/- 0.44 (SD), respectively, and these were significantly lower than the 3.1 +/- 0.36 (SD) score for those with CA12-/CA12-. CONCLUSION: IFN-gamma CA microsatellite polymorphism was associated with the susceptibility of Chinese Han children to RSV and the severity of the infection. PMID- 25130434 TI - Photocatalytic CO2 conversion over alkali modified TiO2 without loading noble metal cocatalyst. AB - Surface modification of TiO2 with NaOH promoted the chemisorption, activation and photocatalytic CO2 reduction. An optimized loading amount of NaOH kept a good balance between CO2 chemisorption quantity and BET surface area of TiO2. This noble metal free method provides a simple pathway for effective multiple H(+)/e( ) CO2 photoreduction. PMID- 25130435 TI - Phylogeny suggests nondirectional and isometric evolution of sexual size dimorphism in argiopine spiders. AB - Sexual dimorphism describes substantial differences between male and female phenotypes. In spiders, sexual dimorphism research almost exclusively focuses on size, and recent studies have recovered steady evolutionary size increases in females, and independent evolutionary size changes in males. Their discordance is due to negative allometric size patterns caused by different selection pressures on male and female sizes (converse Rensch's rule). Here, we investigated macroevolutionary patterns of sexual size dimorphism (SSD) in Argiopinae, a global lineage of orb-weaving spiders with varying degrees of SSD. We devised a Bayesian and maximum-likelihood molecular species-level phylogeny, and then used it to reconstruct sex-specific size evolution, to examine general hypotheses and different models of size evolution, to test for sexual size coevolution, and to examine allometric patterns of SSD. Our results, revealing ancestral moderate sizes and SSD, failed to reject the Brownian motion model, which suggests a nondirectional size evolution. Contrary to predictions, male and female sizes were phylogenetically correlated, and SSD evolution was isometric. We interpret these results to question the classical explanations of female-biased SSD via fecundity, gravity, and differential mortality. In argiopines, SSD evolution may be driven by these or additional selection mechanisms, but perhaps at different phylogenetic scales. PMID- 25130436 TI - In search of the "Holy Grail": will we ever prove the efficacy of Rapid Response Systems (RRS)? PMID- 25130437 TI - Non-coding RNAs: a novel level of genome complexity. PMID- 25130438 TI - Lumisterol is metabolized by CYP11A1: discovery of a new pathway. AB - Lumisterol3 (L3) is produced by photochemical transformation of 7 dehydrocholesterol (7-DHC) during exposure to high doses of ultraviolet B radiation. It has been assumed that L3 is biologically inactive and is not metabolized in the body. However, some synthetic derivatives of L3 display biological activity. The aim of this study was to test the ability of CYP11A1 to metabolize L3. Incubation of L3 with bovine or human CYP11A1 resulted in the formation of three major and a number of minor products. The catalytic efficiency of bovine CYP11A1 for metabolism of L3 dissolved in 2-hydroxypropyl-beta cyclodextrin was approximately 20% of that reported for vitamin D3 and cholesterol. The structures of the three major products were identified as 24 hydroxy-L3, 22-hydroxy-L3 and 20,22-dihydroxy-L3 by NMR. 22-Hydroxy-L3 was further metabolized by bovine CYP11A1 to 20,22-dihydroxy-L3. Both 22-hydroxy-L3 and 20,22-dihydroxy-L3 gave rise to a minor metabolite identified from authentic standard and mass spectrometry as pregnalumisterol (pL) (product of C20-C22 side chain cleavage of L3) and two trihydroxy-L3 products. The capability of tissues expressing CYP11A1 to metabolize L3 was demonstrated using pig adrenal fragments where 20,22-dihydroxy-L3, 22-hydroxy-L3, 24-hydroxy-L3 and pL were detected by LC/MS. Thus, we have established that L3 is metabolized by CYP11A1 to 22- and 24 hydroxy-L3 and 20,22-dihydroxy-L3 as major products, as well as to pL and other minor products. The previously reported biological activity of pL and the presence of CYP11A1 in skin suggest that this pathway may serve to produce biologically active products from L3, emphasizing a novel role of CYP11A1 in sterol metabolism. PMID- 25130439 TI - Endotoxin-induced vascular endothelial cell migration is dependent on TLR4/NF kappaB pathway, NAD(P)H oxidase activation, and transient receptor potential melastatin 7 calcium channel activity. AB - Endothelial dysfunction is decisive and leads to the development of several inflammatory diseases. Endotoxemia-derived sepsis syndrome exhibits a broad inflammation-induced endothelial dysfunction. We reported previously that the endotoxin, lipopolysaccharide (LPS), induces the conversion of endothelial cells (ECs) into activated fibroblasts, showing a myofibroblast-like protein expression profile. Enhanced migration is a hallmark of myofibroblast function. However, the mechanism involved in LPS-induced EC migration is no totally understood. Some studies have shown that the transient receptor potential melastatin 7 (TRPM7) ion channel is involved in fibroblast and tumor cell migration through the regulation of calcium influx. Furthermore, LPS modulates TRPM7 expression. However, whether TRPM7 is involved in LPS-induced EC migration remains unknown. Here, we study the participation of LPS as an inducer of EC migration and study the mechanism underlying evaluating the participation of the TRPM7 ion channel. Our results demonstrate that LPS induced EC migration in a dose-dependent manner. Furthermore, this migratory process was mediated by the TLR-4/NF-kappaB pathway and the generation of ROS through the PKC-activated NAD(P)H oxidase. In addition, LPS increased the intracellular calcium level and the number of focal adhesion kinase (FAK)-positive focal adhesions in EC. Finally, we demonstrate that using TRPM7 blockers or suppressing TRPM7 expression through siRNA successfully inhibits the calcium influx and the LPS-induced EC migration. These results point out TRPM7 as a new target in the drug design for several inflammatory diseases that impair vascular endothelium function. PMID- 25130441 TI - Lack of association of LOXL1 gene variants in Japanese patients with central retinal vein occlusion without clinically detectable pseudoexfoliation material deposits. AB - PURPOSE: A possible association has been reported between exfoliation syndrome (EX) and various ocular and systemic vascular disorders; however, it is unclear if there is an association between EX and central retinal vein occlusion (CRVO). Because latent deposits of exfoliation materials might not be recognized during slit-lamp examination, an ocular biopsy is required to establish a precise diagnosis. We evaluated a possible association between EX and CRVO using lysyl oxidase-like 1 (LOXL1) gene variants as alternative markers for EX. METHODS: The allelic and genotypic frequencies of three LOXL1 variants (rs1048661, rs3825942, and rs2165241) were determined in 68 consecutive Japanese patients with CRVO [15 with exfoliation syndrome (EX+) and 53 without exfoliation syndrome (EX-)] and 90 control patients with cataract without EX (CT). RESULTS: The frequencies of the rs1048661 and rs3825942 variants showed borderline difference between the CRVO and CT groups (p = 0.04085 and p = 0.06088, respectively, for allelic frequencies, and p = 0.06838 and p = 0.03482, respectively, for genotypic frequencies). Compared with the CT group, subgroup analysis showed that the CRVO EX+ group had significant differences in the allelic and genotypic frequencies of rs1048661 (p = 0.0006447 and p = 0.0001392, respectively) and had borderline differences in the allelic and genotypic frequencies of rs3825942 (p = 0.03403 and p = 0.07341, respectively), while the CRVO EX- group did not (p = 0.1324 0.6306). Subgroup analysis showed that the frequencies of rs2165241 did not differ between the CRVO and CT groups. CONCLUSIONS: When the LOXL1 variants were used as disease markers for clinically undetectable EX, there was no association between CRVO and EX. The results suggested that the LOXL1 variants, which are well-established markers for EX, are not likely genetic markers for CRVO in Japanese subjects. PMID- 25130440 TI - Mouse monocyte chemoattractant protein 1 (MCP1) functions as a monomer. AB - Monocyte chemoattractant protein 1 (MCP1) is an important chemoattractant for microglia. Rodent MCP1 carries a heavily glycosylated C-terminus, which has been predicted to increase local MCP1 concentration, promote MCP1 dimerization/oligomerization, and facilitate receptor engagement. Previous studies have shown that MCP1 mutant lacking the glycosylated C-terminus cannot dimerize/oligomerize, but has higher chemotactic potency than the wild-type (full length) MCP1, suggesting that rodent MCP1 may function as a monomer. Although many groups support this hypothesis, there is no direct evidence on whether rodent MCP1 dimer is functional. In this paper, using forced recombinant dimeric MCP1 proteins we show that mouse MCP1 dimer is unable to activate Rac1, promote protrusion of lamellipodia, or induce microglial migration, although it can bind to CCR2 and mediate its internalization. These results support the idea that signaling events mediated by MCP1 require the presence of the monomeric form of this chemokine. PMID- 25130442 TI - How resistant is 'treatment-resistant' obsessive-compulsive disorder in youth? AB - OBJECTIVES: Obsessive-compulsive disorder (OCD) is often perceived as being difficult to treat. This study aimed to test the hypothesis that treatment non response in routine clinical practice is often due to failures in the delivery of treatment, and that most patients who are apparently treatment-resistant will respond to treatment if adequately delivered. DESIGN: Retrospective cohort data analysis. METHODS: Forty-three young people with severe, treatment-resistant OCD (defined as Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS] scores >= 30 and non-response to previous cognitive behaviour therapy [CBT] and selective serotonin reuptake inhibitors) were referred to a specialist clinic and completed a course of manualized CBT, with (N = 21) or without (N = 22) optimization of medication. A sub-sample (N = 15) completed a semi-structured interview to determine characteristics of their previous CBT; quality was assessed according to pre-determined criteria. RESULTS: Specialist treatment was associated with significant reductions in OCD symptoms at post-treatment with gains maintained at 3-month follow-up. At the 3-month follow-up, 58% of patients showed a meaningful clinical response (>= 35% drop on the CY-BOCS) and 22% were in remission (<= 12 on the CY-BOCS). Patients whose medication was optimized tended (non significantly) to have better responses. The quality of previous CBT was assessed in a sub-group of participants and rated as inadequate in 95.5% of cases. The most common inadequacy was insufficient focus on exposure techniques. CONCLUSIONS: These findings provide support for the notion that treatment non response in routine practice may be due to technical treatment failures and highlight the need to disseminate good quality evidence-based treatment among this population. Research is also needed to understand factors that impede outcome to further improve response and remission rates. PRACTITIONER POINTS: Among young people with OCD, failure to respond to treatment in routine clinical practice may often reflect the nature of the treatment received. Exposure techniques may often be overlooked in CBT for OCD, potentially resulting in poor therapeutic response. Most young people with severe and apparent treatment resistant OCD respond to outpatient CBT incorporating E/RP. Further research is needed to establish effective methods for disseminating good quality CBT for OCD. PMID- 25130443 TI - Preliminary characterisation of nanotubes connecting T-cells and their use by HIV 1. AB - BACKGROUND INFORMATION: Cells, especially those of the immune system, can form long and thin connections termed tunnelling nanotubes (TNTs). These structures can reach >100 um in length and, in T-cells, contain actin but no tubulin and are not open ended. T-cell TNTs were found to form following cell contact and to enable the transfer of HIV-1 from an infected- to a connected-T-cell. TNTs are poorly characterised at molecular level. RESULTS: We found Rab11 and tetraspanins, especially CD81, all along T-cells TNTs, whereas Rab4 and Rab35 were absent from these structures. Regarding actin cytoskeleton regulators, Exo70, N-WASP and especially ezrin accumulated at the level of the TNT tip that contacts the connected cell. Phosphoinositides such as PI(4,5)P2 were also concentrated at this level together with HIV-1 Gag. Gag spots on cells and TNTs were essentially immobile, and likely correspond to area of Gag multimerisation for budding to form virus-like particles. Mobility of PHPLCdelta , a specific probe for PI(4,5)P2 , was reduced > threefold at the level of TNT basis or tip compared with the cell body. CONCLUSION: Our study identified the TNT tip as an active zone of actin cytoskeleton reorganisation with the presence of ezrin, Exo70, N-WASP and PI(4,5)P2 . The latter is also known to enable HIV-1 Gag recruitment for viral budding, and the presence of Gag at this level, contacting the connected cell, indicates that the TNT tip is also a favourite place for HIV 1 assembly and budding. PMID- 25130445 TI - Improved tracking performance of Lagrangian block-matching methodologies using block expansion in the time domain: in silico, phantom and in vivo evaluations. AB - The aim of this study was to evaluate tracking performance when an extra reference block is added to a basic block-matching method, where the two reference blocks originate from two consecutive ultrasound frames. The use of an extra reference block was evaluated for two putative benefits: (i) an increase in tracking performance while maintaining the size of the reference blocks, evaluated using in silico and phantom cine loops; (ii) a reduction in the size of the reference blocks while maintaining the tracking performance, evaluated using in vivo cine loops of the common carotid artery where the longitudinal movement of the wall was estimated. The results indicated that tracking accuracy improved (mean = 48%, p < 0.005 [in silico]; mean = 43%, p < 0.01 [phantom]), and there was a reduction in size of the reference blocks while maintaining tracking performance (mean = 19%, p < 0.01 [in vivo]). This novel method will facilitate further exploration of the longitudinal movement of the arterial wall. PMID- 25130444 TI - Comparison of strain and shear wave elastography for the differentiation of benign from malignant breast lesions, combined with B-mode ultrasonography: qualitative and quantitative assessments. AB - Our aim was to compare the diagnostic performance of strain elastography (SE) and shear-wave elastography (SWE), combined with B-mode ultrasonography (US), in breast cancer. For 79 breast lesions that underwent SE and SWE, two radiologists reviewed five data sets (B-mode US, SWE, SE and two combined sets). Qualitative and quantitative elastographic data and Breast Imaging Reporting and Data System (BI-RADS) categories were recorded. The area under the receiver operating characteristic curve (AUC) was evaluated. No significant difference in the AUC between the two elastography methods was noted. After subjective assessment by reviewers, the AUC for the combined sets was improved (SWE, 0.987; SE, 0.982; B mode US, 0.970; p < 0.05). When SE and SWE were added, 38% and 56% of benign BI RADS category 4a lesions with a low suspicion of cancer were downgraded without false-negative results, respectively. SE and SWE performed similarly. Therefore, addition of SE or SWE improved the diagnostic performance of B-mode US, potentially reducing unnecessary biopsies. PMID- 25130447 TI - Computation of the temperature rise at the corneal endothelium during cataract surgery by modeling of heat generation inside the anterior chamber. AB - The corneal endothelium sustaining the transparency of the cornea is a vulnerable cell layer. Thermal exposure during phacoemulsification is considered to be a potential cause of post-operative cell loss. Knowledge of the temperature rise and particularly of its dependence on region and system settings could deliver useful information about a potential correlation with cell damage. However, there exists a lack of understanding of the process and location of heat generation. Analytical calculations and experiments enabled the quantification of different mechanisms acting as heat sources during phacoemulsification. Heat generation caused by viscous friction was estimated using both an analytical approach and a numerical simulation. In contrast to absorption of sound and self-heating of the probe, this effect was ascertained to be the main heat source. Calorimetric measurement of the power input verified this modeling. On the basis of these results, the local temperature distribution inside a porcine eye was computed time dependently using the finite-element method. Two different amplitude settings were compared with respect to the temperature increase at the corneal endothelium. Various conclusions on the mitigation of thermal exposure during treatment can be drawn from this finite-element simulation. PMID- 25130446 TI - Monitoring and staging abdominal aortic aneurysm disease with pulse wave imaging. AB - The abdominal aortic aneurysm (AAA) is a silent and often deadly vascular disease caused by the localized weakening of the arterial wall. Previous work has indicated that local changes in wall stiffness can be detected with pulse wave imaging (PWI), which is a non-invasive technique for tracking the propagation of pulse waves along the aorta at high spatial and temporal resolutions. The aim of this study was to assess the capability of PWI to monitor and stage AAA progression in a murine model of the disease. ApoE/TIMP-1 knockout mice (N = 18) were given angiotensin II for 30 days via subcutaneously implanted osmotic pumps. The suprarenal sections of the abdominal aortas were imaged every 2-3 d after implantation using a 30-MHz VisualSonics Vevo 770 with 15-MUm lateral resolution. Pulse wave propagation was monitored at an effective frame rate of 8 kHz by using retrospective electrocardiogram gating and by performing 1-D cross-correlation on the radiofrequency signals to obtain the displacements induced by the waves. In normal aortas, the pulse waves propagated at constant velocities (2.8 +/- 0.9 m/s, r(2) = 0.89 +/- 0.11), indicating that the composition of these vessels was relatively homogeneous. In the mice that developed AAAs (N = 10), the wave speeds in the aneurysm sac were 45% lower (1.6 +/- 0.6 m/s) and were more variable (r(2) = 0.66 +/- 0.23). Moreover, the wave-induced wall displacements were at least 80% lower within the sacs compared with the surrounding vessel. Finally, in mice that developed fissures (N = 5) or ruptures (N = 3) at the sites of their AAA, higher displacements directed out of the lumen and with no discernible wave pattern (r(2) < 0.20) were observed throughout the cardiac cycle. These findings indicate that PWI can be used to distinguish normal murine aortas from aneurysmal, fissured and ruptured ones. Hence, PWI could potentially be used to monitor and stage human aneurysms by providing information complementary to standard B-mode ultrasound. PMID- 25130448 TI - A new method for measuring the speed of sound in rat liver ex vivo using an ultrasound system: correlation of sound speed with fat deposition. AB - The speed of sound correlates well with the fat content of the liver. Therefore, non-invasive quantification of sound speed in the liver might be of diagnostic value. Here we describe a new non-invasive method that would be clinically applicable for measurement of sound speed in the liver. Sprague-Dawley rats were divided into two groups: a control group and a fatty liver group prepared by keeping the rats on a choline-deficient diet for 6 wk. The livers were subjected to pathologic and biochemical analysis; the speed of sound through the liver tissue was measured using our proposed method and a pulser-receiver as standard. Our results indicated that use of the proposed method makes it feasible to diagnose fatty liver with good accuracy on the basis of sound speed. This approach would have considerable potential for non-invasive diagnosis of fatty liver and would be a valuable adjunct to conventional liver diagnostic procedures. PMID- 25130449 TI - Localized in vivo model drug delivery with intravascular ultrasound and microbubbles. AB - An intravascular ultrasound (IVUS) and microbubble drug delivery system was evaluated in both ex vivo and in vivo swine vessel models. Microbubbles with the fluorophore DiI embedded in the shell as a model drug were infused into ex vivo swine arteries at a physiologic flow rate (105 mL/min) while a 5-MHz IVUS transducer applied ultrasound. Ultrasound pulse sequences consisted of acoustic radiation force pulses to displace DiI-loaded microbubbles from the vessel lumen to the wall, followed by higher-intensity delivery pulses to release DiI into the vessel wall. Insonation with both the acoustic radiation force pulse and the delivery pulse increased DiI deposition 10-fold compared with deposition with the delivery pulse alone. Localized delivery of DiI was then demonstrated in an in vivo swine model. The theoretical transducer beam width predicted the measured angular extent of delivery to within 11%. These results indicate that low frequency IVUS catheters are a viable method for achieving localized drug delivery with microbubbles. PMID- 25130450 TI - Teles-operated echocardiography using a robotic arm and an internet connection. AB - The objective was to design and validate a method of tele-operated echocardiography. The method was tested in a hospital facility with an expert sonographer located in a room 10 m away from the patient. An ultrasound probe, fixed to a motorized probe holder, was located on the patient by a non sonographer and was remotely controlled by the expert sonographer via an Internet connection. Scans were performed on 41 cardiac patients. The quality of the cardiac views obtained using tele-echocardiography was lower than that of reference echocardiography, but generated similar measurements in 93%-100% of the cases. Bland-Altman plots and statistical comparison of tele- and reference echocardiography measures revealed no differences (p > 0.05). Of the 71 valve leaks or aortic stenoses present, 61 (86%) were detected using tele echocardiography. These results indicate that tele-echocardiography provided reliable diagnoses and acceptable measurements in 86% and 93% of cases, respectively, with no false-positive diagnoses being reported. PMID- 25130451 TI - High-intensity focused ultrasound leads to histopathologic changes of the inferior turbinate mucosa with allergic inflammation. AB - This study was aimed at understanding the histopathologic changes that occur in the nasal mucosa of patients with perennial allergic rhinitis after high intensity focused ultrasound (HIFU) treatment. Biopsy specimens of the inferior turbinate mucosa were taken from 11 PAR patients before, immediately after and 1 y after HIFU treatment. Morphometric analysis revealed that the density of eosinophils and other inflammatory cells increased immediately after treatment and then were decreased significantly 1 y post-treatment. Submucosal glands were swollen and venous sinusoids were dilated, but there was no statistically significant change in their density, immediately after treatment. However, both glands and venous sinusoids significantly decreased in number 1 y after HIFU treatment. The ciliated epithelium or basement membrane of the nasal mucosa was well preserved at all stages. In conclusion, HIFU is a tolerable and effective treatment to reduce inflammation of the inferior turbinate mucosa in patients with perennial allergic rhinitis. PMID- 25130452 TI - Reliability of automatic vibratory equipment for ultrasonic strain measurement of the median nerve. AB - The objective of this study was to test the reliability of ultrasonic median nerve strain measurements using automatic vibratory equipment. Strain ratios of the median nerve in the carpal tunnel model and the reference coupler were measured at three different settings of the transducer: 0, +2 and +4 mm (+ = compressing the model down 2-4 mm initially). After measurement of the carpal tunnel model, a +4-mm setting was chosen for in vivo measurement. The median nerve strains of 30 wrists were measured by two examiners using the equipment. Intra- and inter-examiner correlation coefficients (CCs) for the strain ratios were calculated. The closest ratio was found in the +4-mm placement (strain ratio: 0.73, Young's modulus ratio: 0.79). The intra-examiner CC was 0.91 (p < 0.01), and the inter-examiner CCs were 0.72-0.78 (p < 0.01). The automatic vibratory equipment was useful in quantifying median nerve strain at the wrist. PMID- 25130453 TI - Is the frequent sonographic anechoic area distally in metacarpophalangeal joints a sign of arthritis? AB - In clinical practice, ultrasonography (US) often reveals, in the dorsal scan, a small anechoic area distally in both inflamed and clinically non-inflamed metacarpophalangeal joints. This "distal anechogenicity in the metacarpophalangeal joint" (DAEM) might thus be scored false positively as arthritis. We aimed to investigate whether the DAEM is a sign of arthritis. We evaluated the prevalence of DAEMs in 24 non-arthritic subjects. We then compared the dimensions of the DAEM in 10 non-arthritic subjects with a DAEM and 7 consecutive rheumatoid arthritis (RA) outpatients, using 2-D and 3-D ultrasound. Furthermore, we dissected two fresh-frozen postmortem hand specimens after US. A DAEM was observed in the metacarpophalangeal 2 (MCP2) joints of 54% of the 24 non selected non-arthritic individuals; in none of those did the joint exhibit a power Doppler signal. A DAEM was observed in 86% of the 7 RA patients. Dimensions of DAEMs did not statistically significantly differ between these groups. At 3-D imaging and dissection, the DAEM was found to be an extension of the metacarpophalangeal joint capsule. In conclusion, DAEMs occur frequently and are not a sign of arthritis, but are distal joint recesses. This should be taken into account when using current sensitive ultrasonographic scoring systems grading arthritis. PMID- 25130454 TI - A new metric for measuring condition in large predatory sharks. AB - A simple metric (span condition analysis; SCA) is presented for quantifying the condition of sharks based on four measurements of body girth relative to body length. Data on 104 live sharks from four species that vary in body form, behaviour and habitat use (Carcharhinus leucas, Carcharhinus limbatus, Ginglymostoma cirratum and Galeocerdo cuvier) are given. Condition shows similar levels of variability among individuals within each species. Carcharhinus leucas showed a positive relationship between condition and body size, whereas the other three species showed no relationship. There was little evidence for strong differences in condition between males and females, although more male sharks are needed for some species (e.g. G. cuvier) to verify this finding. SCA is potentially viable for other large marine or terrestrial animals that are captured live and then released. PMID- 25130455 TI - Friends interventions in psychosis: a narrative review and call to action. AB - AIMS: To highlight the importance of friendships to young people with psychosis, and the need for clinical interventions to help maintain peer relationships during illness. To structure a research agenda for developing evidence-based interventions with friends. METHOD: An argument is developed through a narrative review of (i) the proven efficacy of family interventions, and (by comparison) a relative absence of friend-based interventions; (ii) the particular primacy of friendships and dating for young people, and typical effects of exclusion; and (iii) reduced friendship networks and dating experiences in psychosis, in pre-, during and post-psychosis phases, also links between exclusion and psychosis. RESULTS: We put forward a model of how poor friendships can potentially be a causal and/or maintenance factor for psychotic symptoms. Given this model, our thesis is that interventions aiming to maintain social networks can be hugely beneficial clinically for young people with psychosis. We give a case study to show how such an intervention can work. CONCLUSIONS: We call for 'friends interventions' for young people with psychosis to be developed, where professionals directly work with a young person's authentic social group to support key friendships and maintain social continuity. An agenda for future research is presented that will develop and test theoretically driven interventions. PMID- 25130457 TI - Effect of truncated neurokinin-1 receptor expression changes on the interaction between human breast cancer and bone marrow-derived mesenchymal stem cells. AB - Previous studies in breast cancer cell lines showed that truncated neurokinin receptor-1 (NK1R-Tr) was able to promote malignant transformation of breast cells, and NK1R-Tr may contribute to tumor progression and promote distant metastasis in human breast cancer. A co-culture model of breast cancer and bone marrow-derived human mesenchymal stem (HMSC-bm) cells showed that HMSC-bm inhibited the growth of breast cancer cells and entered the bone marrow at early stages. Down-regulation of NK1R-Tr may be a key factor in maintaining the quiescent phenotype of breast cancer cells among bone marrow stroma. Stromal derived factor (SDF)-1alpha expression was negatively correlated with NK1R-Tr expression in breast cancer cells. Secretion of SDF-1alpha by HMSC-bm may maintain the quiescent phenotype of breast cancer cells among bone marrow stroma by down-regulating NK1R-Tr expression. Transforming growth factor (TGF)-beta1 expression was positively associated with NK1R-Tr expression in breast cancer cells. In a co-culture system, MDA-MB-231-TGF-beta1I (TGF-beta genes were suppressed using specific shRNA) cells were able to attach to HMSC-bm quickly, indicating that TGF-beta1 was also a key factor for maintaining the quiescent phenotype of breast cancer cells in bone marrow stroma. However, the detailed mechanism still remained unclear and could involve other molecules, in addition to NK1R-Tr. PMID- 25130456 TI - Differential partial activation phenotype and production of tumour necrosis factor-alpha by conventional dendritic cells in response to lipopolysaccharide in HIV+ viraemic subjects and HIV+ controllers. AB - HIV(+) subjects are reported to have increased soluble CD14 (sCD14) in plasma, an indicator of microbial translocation. We evaluated if microbial translocation has a differential impact on the activation and function of conventional dendritic cells (cDC) from viraemic HIV(+) subjects and HIV(+) controllers (CTs). The HIV(+) subjects were classified into two groups according to their plasma viral load (pVL): CT and viraemic. Subjects without HIV were included as controls (HIV( ) ). The frequencies and phenotypes of cDC from these subjects were evaluated by multi-parameter flow cytometry. In addition, peripheral blood mononuclear cells (PBMCs) were stimulated with lipopolysaccharide (LPS) or single-stranded RNA40 (ssRNA40), the phenotype of the cDC and the intracellular production of tumour necrosis factor (TNF)-alpha by the cDC were evaluated by flow cytometry. We observed a partial activation phenotype for the cDC in the viraemic subjects and CTs ex vivo and after LPS activation, which showed differences in the expression of CD40 and CD86. Furthermore, in response to LPS the cDC from the viraemic subjects produced more TNF-alpha compared to the cDC from CTs. Interestingly, the percentage of TNF-alpha(+) cDC was found to be correlated positively with the pVL. The partial activation of cDC and the over-production of TNF-alpha in response to LPS in viraemic HIV(+) subjects might be related to the increased chronic activation observed in these subjects. In contrast, cDC from CTs seem to have a regulated response to LPS, indicating that they respond differently to chronic immune activation. These results may have implications in the development of HIV therapies and vaccines using DC. PMID- 25130459 TI - An update on red blood cell storage lesions, as gleaned through biochemistry and omics technologies. AB - Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high-energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long-stored RBCs and promote the rapid clearance of up to one fourth of long-stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects. PMID- 25130460 TI - Cecropin A-melittin mutant with improved proteolytic stability and enhanced antimicrobial activity against bacteria and fungi associated with gastroenteritis in vitro. AB - Cecropin A-melittin (CAM), a chimeric antimicrobial peptide with potent antimicrobial activity, is threatened by some special extracellular proteases when used to deal with certain drug-resistant pathogenic microbes in the gastrointestinal tract. Thus, a four-tryptophan-substitution mutant (CAM-W) from CAM was developed via the replacement of special amino acid residues to enhance the antimicrobial potency and to improve the proteolytic stability of this agent. The pharmaceutical index of CAM-W was investigated, with a focus on biological potency, cytotoxicity, and proteolytic stability, as well as pH and thermal resistance. CAM-W exhibited potent antimicrobial activity and was approximately 3 12 times higher than that of CAM. CAM-W also exhibited a strong antifungal activity against a series of common pathogenic fungi, in a lower IC50 range between 2.1mg/L and 3.3mg/L than that of its reference CAM ranging from 9.8mg/L to 14.2mg/L. Besides, CAM-W showed moderate cytotoxicity (IC50>300mg/L) in erythrocyte lysis test. In addition, CAM-W overcame challenges under various conditions, including specific temperatures (20, 30, 40, 50, 60, 70, 80, and 90 degrees C), pH values (2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, and 9.0), and proteases (trypsin, pepsin, human neutrophil elastase, Pseudomonas aeruginosa elastase, and Staphylococcus aureus V8 protease) that are commonly present in human gastrointestinal tract. These results suggest that the four-tryptophan substitution can confer CAM-W with a high pharmaceutical index, which is important for CAM-W to become a potential alternative to conventional antibiotics against bacteria and fungi associated with gastroenteritis. PMID- 25130458 TI - Sex-specific behavioral traits in the Brd2 mouse model of juvenile myoclonic epilepsy. AB - Idiopathic generalized epilepsy represents about 30-35% of all epilepsies in humans. The bromodomain BRD2 gene has been repeatedly associated with the subsyndrome of juvenile myoclonic epilepsy (JME). Our previous work determined that mice haploinsufficient in Brd2 (Brd2+/-) have increased susceptibility to provoked seizures, develop spontaneous seizures and have significantly decreased gamma-aminobutyric acid (GABA) markers in the direct basal ganglia pathway as well as in the neocortex and superior colliculus. Here, we tested male and female Brd2+/- and wild-type littermate mice in a battery of behavioral tests (open field, tube dominance test, elevated plus maze, Morris water maze and Barnes maze) to identify whether Brd2 haploinsufficiency is associated with the human behavioral patterns, the so-called JME personality. Brd2+/- females but not males consistently displayed decreased anxiety. Furthermore, we found a highly significant dominance trait (aggression) in the Brd2+/- mice compared with the wild type, more pronounced in females. Brd2+/- mice of either sex did not differ from wild-type mice in spatial learning and memory tests. Compared with wild-type littermates, we found decreased numbers of GABA neurons in the basolateral amygdala, which is consistent with the increase in aggressive behavior. Our results indicate that Brd2+/- haploinsufficient mice show no cognitive impairment but have behavioral traits similar to those found in patients with JME (recklessness, aggression). This suggests that either the BRD2 gene is directly responsible for influencing many traits of JME or it controls upstream regulators of individual phenotypes. PMID- 25130461 TI - Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase. AB - Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-alpha, peroxisome proliferator activated receptor (PPAR)-alpha, and PPAR-gamma. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro atherogenic role of macrophage LPL. PMID- 25130462 TI - Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance. AB - Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-alpha, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls. Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin sensitivity and if testosterone is implicated in muscular insulin resistance in PCOS, this is by and indirect mechanism. PMID- 25130463 TI - PDI family protein ERp29 forms 1:1 complex with lectin chaperone calreticulin. AB - Lectin chaperone calreticulin is well known to interact with ERp57 which is one of PDI family proteins. The interaction of ERp57 with calreticulin is believed to assist disulfide bond formation of nascent glycoprotein in the ER. Various kinds of PDI family proteins are present in the ER, however, their precise roles have been unclear. In this study, interaction assay between PDI family proteins and calreticulin by SPR analysis was performed. Our analysis revealed for the first time formation of a 1:1 complex between ERp29 and calreticulin. The dissociation constant of interaction between ERp29 and calreticulin was shown to be almost identical to ERp57-calreticulin interaction. We speculate that the recognition site of ERp29 within calreticulin is different from that of ERp57. PMID- 25130464 TI - Leucine methylation of protein phosphatase PP4C at C-terminal is critical for its cellular functions. AB - BACKGROUND: Protein phosphatase 4 (PP4) has been known to have critical functions in DNA double strand break (DSB) repair and cell cycle by the regulation of phosphorylation of its target proteins, such as H2AX, RPA2, KAP-1, 53BP1. However, it is largely unknown how PP4 itself is regulated. METHODS: We examined the PP4C methylation on L307 at C-terminal by using methylated-leucine specific antibody. Then with PP4C L307A mutant, we explored that how nonmethylated form of PP4C affects its known cellular functions by immunoprecipitation, immunofluorescence, and DNA DSB repair assays. RESULTS: Here we show that PP4C is methylated on its C-terminal leucine residue in vivo and this methylation is important for cellular functions mediated by PP4. In the cells PP4C L307A mutant has significantly low activity of dephosphorylation against its known target proteins, and the loss of interaction between L307A PP4 mutant and regulatory subunits, R1, R2, or R3alpha/beta causes the dissociation from its target proteins. Moreover, PP4C L307A mutant loses its role in both DSB repair pathways, HR (homologous recombination) and NHEJ (non-homologous end joining), which phenocopies PP4C depletion. CONCLUSION: Our results demonstrate the key site of PP4C methylation and establish the physiological importance of this regulation. PMID- 25130465 TI - Differential impact of glucose levels and advanced glycation end-products on tubular cell viability and pro-inflammatory/profibrotic functions. AB - High glucose (HG) or synthetic advanced glycation end-products (AGE) conditions are generally used to mimic diabetes in cellular models. Both models have shown an increase of apoptosis, oxidative stress and pro-inflammatory cytokine production in tubular cells. However, the impact of the two conditions combined has rarely been studied. In addition, the impact of glucose level variation due to cellular consumption is not clearly characterized in such experiments. Therefore, the aim of this study was to compare the effect of HG and AGE separately and of both on tubular cell phenotype changes in the HK2 cell line. Moreover, glucose consumption was monitored every hour to maintain the glucose level by supplementation throughout the experiments. We thus observed a significant decrease of apoptosis and H2O2 production in the HK2 cell. HG or AGE treatment induced an increase of total and mitochondrial apoptosis as well as TGF beta release compared to control conditions; however, AGE or HG led to apoptosis preferentially involving the mitochondria pathway. No cumulative effect of HG and AGE treatment was observed on apoptosis. However, a pretreatment with RAGE antibodies partially abolished the apoptotic effect of HG and completely abolished the apoptotic effect of AGE. In conclusion, tubular cells are sensitive to the lack of glucose as well as to the HG and AGE treatments, the AGE effect being more deleterious than the HG effect. Absence of a potential synergistic effect of HG and AGE could indicate that they act through a common pathway, possibly via the activation of the RAGE receptors. PMID- 25130466 TI - LOX-1 - dependent mitochondrial DNA damage and NLRP3 activation during systemic inflammation in mice. AB - BACKGROUND: Lectin-like oxidized low-density lipoprotein scavenger receptor-1 (LOX-1) is known to be involved in many pathophysiological events, such as inflammation. METHODS: To clarify the role of LOX-1 in mtDNA damage and NLRP3 inflammasome activation, we studied wild-type (WT) and LOX-1 knockout (KO) mice given thioglycollate, an inflammatory stimulus. RESULTS: We observed intense inflammatory response (CD45 and CD68 expression) and mtDNA damage in spleen and kidneys of WT mice given thioglycollate. The abrogation of LOX-1 (use of LOX-1 knockout mice) reduced the inflammatory response as well as mtDNA damage (P<0.05 vs. WT mice). We also observed that mice with LOX-1 deletion had markedly reduced expression of caspase-1 (P10 and P20 subunits) as well as cleaved IL-1beta and IL 18. These mice also had much less mtDNA damage and only limited NLRP3 inflammasome expression. CONCLUSIONS: These in vivo observations indicate that LOX-1 plays a key role in mtDNA damage which then leads to NLRP3 inflammasome activation during inflammation. PMID- 25130468 TI - Biophysical and biological meanings of healthspan from C. elegans cohort. AB - Lifespan among individuals ranges widely in organisms from yeast to mammals, even in an isogenic cohort born in a nearly uniform environment. Needless to say, genetic and environmental factors are essential for aging and lifespan, but in addition, a third factor or the existence of a stochastic element must be reflected in aging and lifespan. An essential point is that lifespan or aging is an unpredictable phenomenon. The present study focuses on elucidating the biophysical and biological meanings of healthspan that latently indwells a stochastic nature. To perform this purpose, the nematode Caenorhabditis elegans served as a model animal. C. elegans fed a healthy food had an extended healthspan as compared to those fed a conventional diet. Then, utilizing this phenomenon, we clarified a mechanism of healthspan extension by measuring the single-worm ATP and estimating the ATP noise (or the variability of the ATP content) among individual worms and by quantitatively analyzing biodemographic data with the lifespan equation that was derived from a fluctuation theory. PMID- 25130467 TI - Chemical rescue of DeltaF508-CFTR in C127 epithelial cells reverses aberrant extracellular pH acidification to wild-type alkalization as monitored by microphysiometry. AB - Cystic fibrosis (CF) is caused by mutations in the gene for CFTR, a cAMP activated anion channel expressed in apical membranes of wet epithelia. Since CFTR is permeable to HCO3(-), and may regulate bicarbonate exchangers, it is not surprising evidence of changes in extracellular pH (pHo) have been found in CF. Previously we have shown that tracking pHo can be used to differentiate cells expressing wild-type CFTR from controls in mouse mammary epithelial (C127) and fibroblast (NIH/3T3) cell lines. In this study we characterized forskolin stimulated extracellular acidification rates in epithelia where chemical correction of mutant DeltaF508-CFTR converted an aberrant response in acidification (10%+ increase) to wild-type (25%+ decrease). Thus treatment with corrector (10% glycerol) and the resulting increased expression of DeltaF508-CFTR at the surface was detected by microphysiometry as a significant reversal from acidification to alkalization of pHo. These results suggest that CFTR activation as well as correction can be detected by carefully monitoring pHo and support findings in the field that extracellular pH acidification may impact the function of airway surface liquid in CF. PMID- 25130469 TI - NFkappaB activation is essential for miR-21 induction by TGFbeta1 in high glucose conditions. AB - Transforming growth factor beta1 (TGFbeta1) is a pleiotropic growth factor with a very broad spectrum of effects on wound healing. Chronic non-healing wounds such as diabetic foot ulcers express reduced levels of TGFbeta1. On the other hand, our previous studies have shown that the microRNA miR-21 is differentially regulated in diabetic wounds and that it promotes migration of fibroblast cells. Although interplay between TGFbeta1 and miR-21 are studied in relation to cancer, their interaction in the context of chronic wounds has not yet been investigated. In this study, we examined if TGFbeta1 could stimulate miR-21 in fibroblasts that are subjected to high glucose environment. MiR-21 was, in fact, induced by TGFbeta1 in high glucose conditions. The induction by TGFbeta1 was dependent on NFkappaB activation and subsequent ROS generation. TGFbeta1 was instrumental in degrading the NFkappaB inhibitor IkappaBalpha and facilitating the nuclear translocation of NFkappaB p65 subunit. EMSA studies showed enhanced DNA binding activity of NFkappaB in the presence of TGFbeta1. ChIP assay revealed binding of p65 to miR-21 promoter. NFkappaB activation was also required for the nuclear translocation of Smad 4 protein and subsequent direct interaction of Smad proteins with primary miR-21 as revealed by RNA-IP studies. Our results show that manipulation of TGFbeta1-NFkappaB-miR-21 pathway could serve as an innovative approach towards therapeutics to heal diabetic ulcers. PMID- 25130470 TI - Fasting times in serum PSA assay. PMID- 25130471 TI - Prospects for clinically relevant epigenetic tests in the andrology laboratory. PMID- 25130472 TI - Risk prediction models for biochemical recurrence after radical prostatectomy using prostate-specific antigen and Gleason score. AB - Many computer models for predicting the risk of prostate cancer have been developed including for prediction of biochemical recurrence (BCR). However, models for individual BCR free probability at individual time-points after a BCR free period are rare. Follow-up data from 1656 patients who underwent laparoscopic radical prostatectomy (LRP) were used to develop an artificial neural network (ANN) to predict BCR and to compare it with a logistic regression (LR) model using clinical and pathologic parameters, prostate-specific antigen (PSA), margin status (R0/1), pathological stage (pT), and Gleason Score (GS). For individual BCR prediction at any given time after operation, additional ANN, and LR models were calculated every 6 months for up to 7.5 years of follow-up. The areas under the receiver operating characteristic (ROC) curve (AUC) for the ANN (0.754) and LR models (0.755) calculated immediately following LRP, were larger than that for GS (AUC: 0.715; P = 0.0015 and 0.001), pT or PSA (AUC: 0.619; P always <0.0001) alone. The GS predicted the BCR better than PSA (P = 0.0001), but there was no difference between the ANN and LR models (P = 0.39). Our ANN and LR models predicted individual BCR risk from radical prostatectomy for up to 10 years postoperative. ANN and LR models equally and significantly improved the prediction of BCR compared with PSA and GS alone. When the GS and ANN output values are combined, a more accurate BCR prediction is possible, especially in high-risk patients with GS >=7. PMID- 25130474 TI - Hiccups and gastroesophageal reflux disease as seen on high resolution esophageal manometry. PMID- 25130473 TI - Correlates of adolescent and young adult sexual initiation patterns. AB - CONTEXT: Identifying adolescent characteristics associated with different patterns of sexual initiation is critical to promoting healthy sexual development. METHODS: Patterns of sexual initiation were examined among 12,378 respondents to Waves 1 (1994-1995) and 4 (2008) of the National Longitudinal Study of Adolescent Health. Multinomial logistic regression explored associations between adolescent characteristics and membership in five latent classes capturing the timing, sequence, pace and variety of sexual initiation patterns. RESULTS: Age and indicators of greater psychosocial conventionality were associated with membership in the atypical "postponers" class (characterized by postponement of oral, vaginal and anal sexual activity until early adulthood), although patterns of associations varied by gender. For example, compared with males who attended religious services at least once a week, males who never attended religious services were more likely to appear in the vaginal initiators/multiple behaviors class (characterized by initiation of vaginal sex first and then initiation of another behavior after at least one year), rather than in the postponers class (relative risk ratio, 2.5). Compared with women who prayed at least once a day, those who never prayed were more likely to be in the vaginal initiators/single behavior class (whose members typically engaged in only one type of behavior), rather than in the postponers class (2.0). CONCLUSIONS: Individuals who are more adherent, and presumably more committed, to the attitudes, values and expectations of conventional society are more likely than others to delay multiple types of sexual activity until well beyond the norm for their peers. PMID- 25130475 TI - Validation of mechanical, electrical and thermal nociceptive stimulation methods in horses. AB - REASONS FOR PERFORMING STUDY: To validate a model for investigating the effects of analgesic drugs on mechanical, thermal and electrical stimulation testing. OBJECTIVES: To investigate repeatability, sensitivity and specificity of nociceptive tests. STUDY DESIGN: Randomised experiment with 2 observers in 2 phases. METHODS: Mechanical (M), thermal (TL) and electrical (E) stimuli were applied to the dorsal metacarpus (M-left and TL-right) and coronary band of the left thoracic limb (E) and a thoracic thermal stimulus (TT) was applied caudal to the withers in 8 horses (405 +/- 43 kg). Stimuli intensities were increased until a clear avoidance response was detected without exceeding 20 N (M), 60 degrees C (TL and TT) and 15 V (E). For each set of tests, 3 real stimuli and one sham stimulus were applied (32 per animal) using a blinded, randomised, crossover design repeated after 6 months. A distribution frequency and, for each stimulus, Chi-square and McNemar tests compared both the proportion of positive responses detected by 2 observers and the 2 study phases. The kappa coefficients estimated interobserver agreement in determining endpoints. Sensitivity (384 tests) and specificity (128 tests) were evaluated for each nociceptive stimulus to assess the evaluators' accuracy in detecting real and sham stimuli. RESULTS: Nociceptive thresholds were 3.1 +/- 2 N (M), 8.1 +/- 3.8 V (E), 51.4 +/- 5.5 degrees C (TL) and 55.2 +/- 5.3 degrees C (TT). The level of agreement after all tests, M, E, TL and TT, was 90, 100, 84, 98 and 75%, respectively. Sensitivity was 89, 100, 89, 98 and 70% and specificity 92, 97, 88, 91 and 94%, respectively. CONCLUSIONS: The high interobserver agreement, sensitivity and specificity suggest that M, E and TL tests are valid for pain studies in horses and are suitable tools for investigating antinociceptive effects of analgesics in horses. PMID- 25130476 TI - Sequential ofatumumab and lenalidomide for the treatment of relapsed and refractory chronic lymphocytic leukemia and small lymphocytic lymphoma. AB - Ofatumumab is a fully human anti-CD20 monoclonal antibody with enhanced antibody dependent and complement dependent cytotoxicity. Lenalidomide induces T cell and natural killer (NK) cell activation and in vitro enhances clearance of chronic lymphocytic leukemia (CLL) cells by monoclonal antibodies. We performed a multi center, phase 2 trial of sequential treatment with ofatumumab and lenalidomide in patients with advanced, relapsed and refractory (R/R) CLL, consisting of ofatumumab 2000 mg intravenously on day 1 and lenalidomide 10 mg on days 8-28, for up to six cycles. Twenty-one subjects were included with median age of 63 years and two prior lines of therapy. The overall response rate was 47.6% and 23.8% had stable disease. Median overall survival was 21.5 months. Neutropenia and thrombocytopenia were the most frequent adverse events. Tumor flare reaction occurred in 43% of subjects. Intracycle sequential ofatumumab plus lenalidomide is active in high-risk R/R CLL and well tolerated except for frequent cytopenias. PMID- 25130477 TI - Activating somatic mutations in diffuse large B-cell lymphomas: lessons from next generation sequencing and key elements in the precision medicine era. AB - Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma, accounting for 30-40% of newly diagnosed non-Hodgkin lymphomas. Historically, DLBCL has been thought to involve recurrent translocations of the immunoglobulin heavy (IGH) locus and the deregulation of rearranged oncogenes. Whole exome sequencing (WES) of more than 200 DLBCLs has completely redefined the genetic landscape of the disease by identifying recurrent single nucleotide variants and providing new therapeutic opportunities in DLBCL molecular subtypes. Some of these somatic mutations target genes that play a crucial role in B-cell function (B cell receptor [BCR] signaling, nuclear factor kappaB [NF-kappaB] pathway, Toll like receptor [TLR] signaling and phosphatidylinositol 3-kinase [PI3K] pathway), immunity, cell cycle/apoptosis or chromatin modification. In this review, following an overview of the somatic mutations reported in DLBCL, we focus on activating and clustered mutations targeting genes including MYD88, CD79A/B, EZH2 and CARD11 and discuss their clinical and therapeutic relevance in the precision medicine era. PMID- 25130480 TI - Interface control of the magnetic chirality in CoFeB/MgO heterostructures with heavy-metal underlayers. AB - Recent advances in the understanding of spin orbital effects in ultrathin magnetic heterostructures have opened new paradigms to control magnetic moments electrically. The Dzyaloshinskii-Moriya interaction (DMI) is said to play a key role in forming a Neel-type domain wall that can be driven by the spin Hall torque. Here we show that the strength and sign of the DMI can be changed by modifying the adjacent heavy-metal underlayer (X) in perpendicularly magnetized X/CoFeB/MgO heterostructures. The sense of rotation of a domain wall spiral is reversed when the underlayer is changed from Hf, Ta to W and the strength of DMI varies as the filling of 5d orbitals, or the electronegativity, of the heavy metal layer changes. The DMI can even be tuned by adding nitrogen to the underlayer, thus allowing interface engineering of the magnetic texture in ultrathin magnetic heterostructures. PMID- 25130479 TI - Estradiol induces gene proximity and MLL-MLLT3 fusion in an activation-induced cytidine deaminase-mediated pathway. AB - Epidemiological data have linked birth control formulations to an increased risk of infant acute leukemia involving MLL rearrangements. Reverse transcription polymerase chain reaction (RT-PCR) studies showed that 10 nM estradiol enhanced MLL transcription in addition to its common translocation partners, MLLT2 (AF4) and MLLT3 (AF9). The same concentration of estradiol triggered MLL and MLLT3 co localization without affecting the interaction of genes located on the same chromosomes. Estradiol also stimulated the generation of MLL-MLLT3 fusion transcripts as seen by RT-PCR. RNAi knockdown of activation-induced cytidine deaminase (AICDA) suppressed the induction of MLL-MLLT3 fusion transcript formation observed with estradiol. Additionally, chromatin immunoprecipitation (ChIP) analysis showed estradiol dependent localization of AICDA in MLL intron 11, upstream of a hotspot for both DNA cleavage and rearrangement, but not downstream within intron 12. Combined, these studies show that levels of estradiol consistent with that observed during pregnancy have the potential to initiate MLL fusions through an AICDA-mediated mechanism. PMID- 25130478 TI - Assessment of carbonic anhydrase IX expression and extracellular pH in B-cell lymphoma cell line models. AB - The expression of carbonic anhydrase IX (CA IX) and its relationship to acidosis in lymphomas has not been widely studied. We investigated the protein expression of CA IX in a human B-cell lymphoma tissue microarray, and in Raji, Ramos and Granta 519 lymphoma cell lines and tumor models, while also investigating the relationship with hypoxia. An imaging method, acidoCEST magnetic resonance imaging (MRI), was used to estimate lymphoma xenograft extracellular pH (pHe). Our results showed that clinical lymphoma tissues and cell line models in vitro and in vivo had moderate CA IX expression. Although in vitro studies showed that CA IX expression was induced by hypoxia, in vivo studies did not show this correlation. Untreated lymphoma xenograft tumor pHe had acidic fractions, and an acidity score was qualitatively correlated with CA IX expression. Therefore, CA IX is expressed in B-cell lymphomas and is qualitatively correlated with extracellular acidosis in xenograft tumor models. PMID- 25130481 TI - Aqueous route to facile, efficient and functional silica coating of metal nanoparticles at room temperature. AB - Various metal (Ag, Au, and Pt)@thiol-functionalized silica (SiO2-SH) nanoparticles (NPs) are successfully prepared at room temperature by a facile, efficient, functional, universal and scalable coating process in alcohol-free aqueous solution using pre-hydrolyzed 3-(mercaptopropyl)trimethoxysilane (MPTMS). The controlled pre-hydrolysis of the silane precursor in water and the consecutive condensation processes are the key to achieve the effective and uniform silica coating on metal NPs in aqueous solution. The thickness of the silica shell is tuned by simply varying the coating time. The silica shell can act as an effective protecting layer for Ag NPs in Ag@SiO2-SH NPs under conditions for silica coating in aqueous solution; however, it leads to a directional dissolution of Ag NPs in a more strongly basic ammonia solution. The environmentally friendly silica coating process in water is also applied to prepare highly surface-enhanced Raman scattering (SERS)-active Ag@SiO2-SH NPs with different types of Raman molecules for highly sensitive SERS-based applications in various fields. PMID- 25130482 TI - Spectroscopic analysis of catalytic water oxidation by [Ru(II)(bpy)(tpy)H2O]2+ suggests that Ru(V)?O is not a rate-limiting intermediate. AB - Modern chemistry's grand challenge is to significantly improve catalysts for water splitting. Further progress requires detailed spectroscopic and computational characterization of catalytic mechanisms. We analyzed one of the most studied homogeneous single-site Ru catalysts, [Ru(II)(bpy)(tpy)H2O](2+) (where bpy = 2,2'-bipyridine, tpy = 2,2';6',2"-terpyridine). Our results reveal that the [Ru(V)(bpy)(tpy)?O](3+) intermediate, reportedly detected in catalytic mixtures as a rate-limiting intermediate in water activation, is not present as such. Using a combination of electron paramagnetic resonance (EPR) and X-ray absorption spectroscopy, we demonstrate that 95% of the Ru complex in the catalytic steady state is of the form [Ru(IV)(bpy)(tpy)?O](2+). [Ru(V)(bpy)(tpy)?O](3+) was not observed, and according to density functional theory (DFT) analysis, it might be thermodynamically inaccessible at our experimental conditions. A reaction product with unique EPR spectrum was detected in reaction mixtures at about 5% and assigned to Ru(III)-peroxo species with ( OOH or -OO- ligands). We also analyzed the [Ru(II)(bpy)(tpy)Cl](+) catalyst precursor and confirmed that this molecule is not a catalyst and its oxidation past Ru(III) state is impeded by a lack of proton-coupled electron transfer. Ru Cl exchange with water is required to form active catalysts with the Ru-H2O fragment. [Ru(II)(bpy)(tpy)H2O](2+) is the simplest representative of a larger class of water oxidation catalysts with neutral, nitrogen containing heterocycles. We expect this class of catalysts to work mechanistically in a similar fashion via [Ru(IV)(bpy)(tpy)?O](2+) intermediate unless more electronegative (oxygen containing) ligands are introduced in the Ru coordination sphere, allowing the formation of more oxidized Ru(V) intermediate. PMID- 25130483 TI - The Mirror Program: Preparing Women for the Postoperative Mastectomy Mirror Viewing Experience. AB - PROBLEM: Preparing women for the experiences they will endure during the breast cancer trajectory improves psychological outcomes and quality of life. Women have found that it may be difficult to view themselves in a mirror after having a mastectomy. Supporting women who have had a mastectomy in mirror-viewing and body image is a relatively new yet important intervention in oncology nursing. METHODS: The feasibility of a preoperative mirror program given by oncology nurse navigators to women who were scheduled for a mastectomy was examined in this randomized control study. FINDINGS: Pre- and postoperative data on anxiety, body image, depression, emotional well-being, and mirror use were collected from intervention participants (n = 10) and control subjects (n = 9). CONCLUSION: This article illustrates the development of the mirror program and the results of the feasibility trial, and provides a discussion with implications for future research. PMID- 25130484 TI - Let-7a is differentially expressed in bronchial biopsies of patients with severe asthma. AB - Asthma is a chronic inflammatory disease. Around 5 to 10% of patients classified as having severe asthma can-not be adequately controlled despite the use of all currently available therapeutic approaches. Previous studies have revealed the potential important role of miRNAs in the regulation of a variety of inflammatory processes, including asthma. Expression of selected miRNAs, specifically let-7a, miR-21 and miR-223, that were shown to have important roles in asthma pathogenesis, were analyzed in bronchial biopsies of 24 patients with asthma, 12 mild and 12 severe, and 10 controls with no chronic disease. We found significantly reduced expression of let-7a in bronchial biopsies from patients with severe asthma in comparison to patients with mild asthma as well as in comparison to the non-asthmatic controls. On the other hand, no significant differences in miR-21 and miR-223 expression were found between the different groups analyzed. Reduced let-7a levels in bronchial biopsies of patients with severe therapy-resistant asthma could not only be used as a potential biomarker to discriminate between different asthma phenotypes, but also might be a target for modulation of treatment at the inflammatory site for a group of patients that are most affected and still lack effective treatment. PMID- 25130485 TI - Interfacial molecular restructuring of plasticized polymers in water. AB - Upon water contact, phthalate-plasticized poly(vinyl chloride) (PVC) surfaces are highly unstable because the plasticizer molecules are not covalently bound to the polymer network. As a result, it is difficult to predict how the surface polymer chains and plasticizers may interact with water without directly probing the plastic/water interface in situ. We successfully studied the molecular surface restructuring of 10 wt% and 25 wt% bis 2-ethylhexyl phthalate (DEHP)-plasticized and pure PVC films (deposited on solid substrates) in situ due to water contact using sum frequency generation (SFG) vibrational spectroscopy. SFG spectral signals from both the top and the bottom of the plastic film were obtained simultaneously, so a thin-film model spectral analysis was applied to separately identify the molecular changes of plastics at the surface and the plastic/substrate interface in water. It was found that in water both the structures of the plastic surface and the buried plastic/substrate interface changed. After removing the samples from the water and exposing them to air again, the surface structures did not completely recover. Further SFG experiments confirmed that small amounts of DEHP were transferred into the water. The leached DEHP molecules could reorder and permanently transfer to new surfaces through water contact. Our studies indicate that small amounts of phthalates can transfer from surface to surface through water contact in an overall scope of minutes. This study yields vital new information on the molecular surface structures of DEHP plasticized PVC in water, and the transfer behaviors and environmental fate of plasticizers in polymers. PMID- 25130486 TI - Effect of LEPR, ABCG2 and SCD1 gene polymorphisms on reproductive traits in the Iranian Holstein cattle. AB - During the last decades, genetic selection for milk production traits has led to increased fertility and health problems in dairy cattle. The aim of this study was to investigate the impact of three polymorphisms located in the ATP-binding cassette superfamily G member 2 transporter (ABCG2), stearoyl-CoA desaturase 1 (SCD1) and leptin receptor (LEPR) genes on reproductive traits and somatic cell count (SCC). The analysis was conducted on 408 randomly selected cows. The SNPs within the genes (LEPR, ABCG2 and SCD1) were genotyped using the PCR-RFLP method. All three possible genotypes were observed for SCD1-T878C and LEPR-T945M SNPs, but not for ABCG2-Y581S SNP. LEPR-T945M and ABCG2-Y581S SNPs had no statistically significant effect on the studied reproductive traits and SCC. However, SCD1 T878C SNP were negatively and significantly related to pregnancy length, dry days and open days (p < 0.05), which lead to decreased profitability in dairy herds. The results suggest that the T878C SNP of SCD1 might be useful as a DNA marker to decrease reproductive problems and improve production traits in Iranian Holstein dairy cows. PMID- 25130487 TI - Identifying predictors of hospital readmission following congenital heart surgery through analysis of a multiinstitutional administrative Database. AB - BACKGROUND: Despite resource burdens associated with hospital readmission, there remains little multiinstitutional data available to identify children at risk for readmission following congenital heart surgery. METHODS AND RESULTS: Children undergoing congenital heart surgery and discharged home between January of 2011 and December 2012 were identified within the Pediatric Health Information System database, a multiinstitutional collection of clinical and administrative data. Patient discharges were assigned to derivation and validation cohorts for the purposes of predictive model design, with 17 871 discharges meeting inclusion criteria. Readmission within 30 days was noted following 956 (11%) of discharges within the derivation cohort (n = 9104), with a median time to readmission of 9 days (interquartile range [IQR] 5-18 days). Readmissions resulted in a rehospitalization length of stay of 4 days (IQR 2-8 days) and were associated with an intensive care unit (ICU) admission in 36% of cases. Independent perioperative predictors of readmission included Risk Adjustment in Congenital Heart Surgery score of 6 (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.8 3.7, P < .001) and ICU length of stay of at least 7 days (OR 1.9 95% CI 1.6-2.2, P < .001). Demographic predictors included Hispanic ethnicity (OR 1.2, 95% CI 1.1 1.4, P = .014) and government payor status (OR 1.2, 95% CI 1.1-1.4, P = .007). Predictive model performance was modest among validation cohort (c statistic 0.68, 95% CI 0.66-0.69, P < .001). CONCLUSIONS: Readmissions following congenital heart surgery are common and associated with significant resource consumption. While we describe independent predictors that may identify patients at risk for readmission prior to hospital discharge, there likely remains other unreported factors that may contribute to readmission following congenital heart surgery. PMID- 25130488 TI - A prognosis based classification of undifferentiated uterine sarcomas: identification of mitotic index, hormone receptors and YWHAE-FAM22 translocation status as predictors of survival. AB - Undifferentiated uterine sarcomas (UUS) are rare tumors with a heterologous biology and a poor prognosis. The goal of this study was to examine clinicopathology, biomarkers and YWHAE-FAM22 translocation status, in the prognosis of these tumors. Twenty-six cases of UUS were included. All original slides were rereviewed and age at diagnosis, tumor stage, "Kurihara" diagnosis, mitotic index, presence of necrosis and grade of nuclear atypia were recorded. Additionally, a tissue microarray was constructed from 22 of the cases, and the protein biomarkers P53, P16, Ki-67, Cyclin-D1, ER, PR and ANLN were evaluated by immunohistochemistry. All tumors were evaluated for the presence of a YWHAE-FAM translocation; the translocation was demonstrated in the three Cyclin-D1 positive tumors. Follow-up data in the form of overall survival were available on all patients. These tumors could be divided into two prognostic groups, a high mitotic index group (10 cases, M = 36.8, SD = 5.4) and a low mitotic index group (16 cases, M = 8.7, SD = 5.8). These two groups showed a statistically significant difference in prognosis. The expression of ER, PR or presence of the YWHAE-FAM22 translocation correlated with low mitotic index and an additionally improved prognosis, although the number of cases was small. These results indicate that UUS can be divided into two prognostic groups using mitotic index as a primary criteria, followed by expression of either ER, PR or the presence of a YWHAE-FAM22 translocation as a secondary criteria. This study demonstrates the presence of statistically significant prognostic subgroups within UUS, and provides treatment insights. PMID- 25130490 TI - Electron confurcation in anaerobic lactate oxidation. PMID- 25130489 TI - Characterizing methyl-bearing side chain contacts and dynamics mediating amyloid beta protofibril interactions using 13C(methyl)-DEST and lifetime line broadening. AB - Many details pertaining to the formation and interactions of protein aggregates associated with neurodegenerative diseases are invisible to conventional biophysical techniques. We recently introduced (15)N dark-state exchange saturation transfer (DEST) and (15)N lifetime line-broadening to study solution backbone dynamics and position-specific binding probabilities for amyloid beta (Abeta) monomers in exchange with large (2-80 MDa) protofibrillar Abeta aggregates. Here we use (13)C(methyl)DEST and lifetime line-broadening to probe the interactions and dynamics of methyl-bearing side chains in the Abeta protofibril-bound state. We show that all methyl groups of Abeta40 populate direct-contact bound states with a very fast effective transverse relaxation rate, indicative of side-chain-mediated direct binding to the protofibril surface. The data are consistent with position-specific enhancements of (13)C(methyl)-R2(tethered) values in tethered states, providing further insights into the structural ensemble of the protofibril-bound state. PMID- 25130491 TI - Dnmt3a and Dnmt3b have overlapping and distinct functions in hematopoietic stem cells. AB - Epigenetic regulation of hematopoietic stem cells (HSCs) ensures lifelong production of blood and bone marrow. Recently, we reported that loss of de novo DNA methyltransferase Dnmt3a results in HSC expansion and impaired differentiation. Here, we report conditional inactivation of Dnmt3b in HSCs either alone or combined with Dnmt3a deletion. Combined loss of Dnmt3a and Dnmt3b was synergistic, resulting in enhanced HSC self-renewal and a more severe block in differentiation than in Dnmt3a-null cells, whereas loss of Dnmt3b resulted in a mild phenotype. Although the predominant Dnmt3b isoform in adult HSCs is catalytically inactive, its residual activity in Dnmt3a-null HSCs can drive some differentiation and generates paradoxical hypermethylation of CpG islands. Dnmt3a/Dnmt3b-null HSCs displayed activated beta-catenin signaling, partly accounting for the differentiation block. These data demonstrate distinct roles for Dnmt3b in HSC differentiation and provide insights into complementary de novo methylation patterns governing regulation of HSC fate decisions. PMID- 25130493 TI - Individual patient data from registrational trials of silodosin in the treatment of non-neurogenic male lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH): subgroup analyses of efficacy and safety data. AB - OBJECTIVE: To evaluate efficacy and safety of silodosin in a pooled analysis of individual patient data from three registrational randomised controlled trials (RCTs) comparing silodosin and placebo in patients with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: A pooled analysis of 1494 patients from three 12-week, multicentre, double-blind, placebo-controlled phase III RCTs was performed. Efficacy and safety data were assessed across patients with different baseline characteristics. RESULTS: Silodosin was significantly more effective than placebo in improving all International Prostate Symptom Score (IPSS)-related parameters, and maximum urinary flow rate (Qmax ) regardless of patients age (P < 0.041). Comparing the efficacy of silodosin in the different age groups, there were no differences for all the IPSS-related parameters, whereas Qmax improvement was slightly higher in patients aged <65 years (P = 0.009). Silodosin was significantly more effective than placebo in reducing all IPSS-related parameters regardless of baseline IPSS (P <= 0.001). Similarly, silodosin was more effective than placebo in improving IPSS-related parameters regardless of baseline Qmax (P <= 0.02). Silodosin was associated with significantly higher adverse event (AE) rates, compared with placebo, in all patient subgroups, with retrograde ejaculation being the most common. Prevalence of dizziness, orthostatic hypotension, and discontinuation rate was similar with silodosin and placebo in most patient subgroups. CONCLUSIONS: We analysed the efficacy and safety of silodosin in several patient subgroups, showing that silodosin was more effective than placebo in improving all IPSS-related parameters in all patient subgroups, whereas AEs were similar. Notably, cardiovascular AEs were not higher in patients taking antihypertensive drugs or with mild renal function impairment. Discontinuation rates due to AEs were lower in elderly patients. PMID- 25130492 TI - Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. AB - The liver is thought to utilize facultative stem cells, also known as "oval cells" or "atypical ductal cells" (ADCs), for regeneration following various types of injury. However, this notion has been based largely on in vitro studies and transplantation models; where lineage tracing has been used, results have been conflicting and effect sizes have been small. Here, we used genetic and nucleoside analog-based tools to mark and track the origin and contribution of various cell populations to liver regeneration in vivo following several ADC inducing insults. We report that, contrary to prevailing stem-cell-based models of regeneration, virtually all new hepatocytes come from preexisting hepatocytes. PMID- 25130495 TI - Investigation of pediatric neck response and muscle activation in low-speed frontal impacts. AB - Pediatric necks present different responses and injury patterns compared with those of adults in motor vehicle crashes (MVCs). To evaluate the effect of different muscle modeling methodologies, three muscle models were developed and simulated under low-speed frontal impact conditions with an average peak acceleration of 3g's. The muscle activation curve for the curve-guided model, the muscle segment was curved using guiding nodes, was further optimized based on experimental data. The pediatric neck model was also simulated under more severe frontal impact conditions with an average peak acceleration of 8g's. Simulation results revealed that the curve-guided model needed more muscle force than the straight-guided model, in which the muscle segment was straight with guiding nodes, and the curve-constrained model, in which the muscle segment was curved without guiding nodes and which imposes more constraints on the head and neck than the curve-guided model. The predicted head responses for the child finite element neck model were within or close to the experimental corridors of 3- and 8 g's frontal impacts. The neck injuries for a 10-year-old child commonly occurred at the interspinous ligament in the C7-T1 segment. The model could be used to analyze the responses and injuries of pediatric neck and head in low-speed frontal impacts. PMID- 25130494 TI - Comparison of therapeutic results from radiofrequency ablation and stereotactic body radiotherapy in solitary lung tumors measuring 5 cm or smaller. AB - BACKGROUNDS: This retrospective study was conducted to compare the clinical outcomes of radiofrequency ablation (RFA) with those of stereotactic body radiotherapy (SBRT) in patients with lung tumors. METHODS: Local tumor progression, adverse events, and overall survival were compared in patients who underwent either RFA or SBRT for a single lung tumor measuring 5 cm or smaller. This study was approved by the institutional review boards of two institutions. Informed consent was waived. RESULTS: During September 2009 to June 2012, 48 patients [30 males and 18 females, with a mean age +/- standard deviation (SD) of 75.0 +/- 7.5 years] underwent RFA at one institution and 47 patients (21 males and 26 females, with a mean age +/- SD of 77.0 +/- 7.5 years) underwent SBRT in another. The mean maximum tumor diameter +/- SD was 2.0 +/- 0.8 cm (range 0.6-3.9 cm) in the RFA group, and 2.1 +/- 0.9 cm (range 0.8-4.7 cm, p = 0.539) in the SBRT group. The RFA and SBRT groups showed similar 3-year local tumor progression [9.6%, 95% confidence interval (CI) 3.6-23.9% vs. 7.0%, 95% CI 0.2-20.2%, p = 0.746] and overall survival rates (86.4%, 95% CI 69.2-94.3% vs. 79.6%, 95% CI 60.6-90.1%, p = 0.738). No factor significantly affected local tumor progression. A maximum tumor size of 2 cm was identified as a prognostic factor in both univariate and multivariate analyses. No death was related to treatment procedures. Major complication rates (Grade 3 adverse events) of the RFA (10.4%, 5/48) and SBRT (8.5%, 4/47, p > 0.999) groups were similar. CONCLUSION: For lung tumor patients, lung RFA provided local tumor control and survival that were similar to those achieved using SBRT, with equal safety. PMID- 25130496 TI - Effectiveness of a stress management program to enhance perimenopausal women's ability to cope with stress. AB - AIM: To evaluate the effectiveness of a stress management program to enhance the ability to cope with stress in perimenopausal women. METHODS: In this quasi experimental design, a stress management program was provided to an experimental group (n = 55), while a control group (n = 42) was given an informational pamphlet. The stress management program included a short lecture, group discussion, and hands-on training in 2 h sessions once a week for 3 weeks. Participants were recruited through a public announcement. Data were collected before and after the intervention, and 1 month following the intervention. The ability to cope with stress was the primary outcome, while psychological well being and relief of symptoms were the secondary outcomes. The primary purpose of this program is to enhance the ability to cope with stress. Therefore, the aspects of knowledge, coping flexibility, and manageability were measured in the resultant ability to cope with stress. RESULTS: Compared to the control group, knowledge in the experimental group improved positively as the primary outcome (P < 0.01). Changes in coping flexibility were demonstrated within the experimental group (P < 0.05). A comparison between groups for the secondary outcome of psychological well-being showed that personal growth (P < 0.05) and happiness (P < 0.01) significantly improved in the experimental group. In addition, the secondary outcome of relief of symptoms indicated not improved. CONCLUSION: Results suggest that the stress management program has the potential to boost perimenopausal women's ability to cope with stress and improve their psychological well-being. PMID- 25130497 TI - Isoform-selective regulation of glycogen phosphorylase by energy deprivation and phosphorylation in astrocytes. AB - Glycogen phosphorylase (GP) is activated to degrade glycogen in response to different stimuli, to support both the astrocyte's own metabolic demand and the metabolic needs of neurons. The regulatory mechanism allowing such a glycogenolytic response to distinct triggers remains incompletely understood. In the present study, we used siRNA-mediated differential knockdown of the two isoforms of GP expressed in astrocytes, muscle isoform (GPMM), and brain isoform (GPBB), to analyze isoform-specific regulatory characteristics in a cellular setting. Subsequently, we tested the response of each isoform to phosphorylation, triggered by incubation with norepinephrine (NE), and to AMP, increased by glucose deprivation in cells in which expression of one GP isoform had been silenced. Successful knockdown was demonstrated on the protein level by Western blot, and on a functional level by determination of glycogen content showing an increase in glycogen levels following knockdown of either GPMM or GPBB. NE triggered glycogenolysis within 15 min in control cells and after GPBB knockdown. However, astrocytes in which expression of GPMM had been silenced showed a delay in response to NE, with glycogen levels significantly reduced only after 60 min. In contrast, allosteric activation of GP by AMP, induced by glucose deprivation, seemed to mainly affect GPBB, as only knockdown of GPBB, but not of GPMM, delayed the glycogenolytic response to glucose deprivation. Our results indicate that the two GP isoforms expressed in astrocytes respond to different physiological triggers, therefore conferring distinct metabolic functions of brain glycogen. PMID- 25130498 TI - Robustness to noise of arterial blood flow estimation methods in CT perfusion. AB - BACKGROUND: Perfusion CT is a technology which allows functional evaluation of tissue vascularity. Due to this potential, it is finding increasing utility in oncology. Although since its introduction continuous advances have interested CT technique, some issues have to be still defined, concerning both clinical and technical aspects. In this study, we dealt with the comparison of two widely employed mathematical models (dual input one compartment model - DOCM - and maximum slope - SM -) analyzing their robustness to the noise. METHODS: We carried out a computer simulation process to quantify effect of noise on the evaluation of an important perfusion parameter (Arterial Blood Flow - BFa) in liver tumours. A total of 4500 liver TAC, corresponding to 3 fixed BFa values, were simulated using different arterial and portal TAC (computed from 5 real CT images) at 10 values of signal to noise ratio (SNR). BFa values were calculated by applying four different algorithms, specifically developed, to these noisy simulated curves. Three algorithms were developed to implement SM (one semiautomatic, one automatic and one automatic with filtering) and the last for the DOCM method. RESULTS: In all the simulations, DOCM provided the best results, i.e., those with the lowest percentage error compared to the reference value of BFa. Concerning SM, the results are variable. Results obtained with the automatic algorithm with filtering are close to the reference value, but only if SNR is higher than 50. Vice versa, results obtained by means of the semiautomatic algorithm gave, in all simulations, the lowest results with the lowest standard deviation of the percentage error. CONCLUSIONS: Since the use of DOCM is limited by the necessity that portal vein is visible in CT scans, significant restriction for patients' follow-up, we concluded that SM can be reliably employed. However, a proper software has to be used and an estimation of SNR would be carried out. PMID- 25130499 TI - Rapid one-step purification of single-cells encapsulated in alginate microcapsules from oil to aqueous phase using a hydrophobic filter paper: implications for single-cell experiments. AB - By virtue of the biocompatibility and physical properties of hydrogel, picoliter sized hydrogel microcapsules have been considered to be a biometric signature containing several features similar to that of encapsulated single cells, including phenotype, viability, and intracellular content. To maximize the experimental potential of encapsulating cells in hydrogel microcapsules, a method that enables efficient hydrogel microcapsule purification from oil is necessary. Current methods based on centrifugation for the conventional stepwise rinsing of oil, are slow and laborious and decrease the monodispersity and yield of the recovered hydrogel microcapsules. To remedy these shortcomings we have developed a simple one-step method to purify alginate microcapsules, containing a single live cell, from oil to aqueous phase. This method employs oil impregnation using a commercially available hydrophobic filter paper without multistep centrifugal purification and complicated microchannel networks. The oil-suspended alginate microcapsules encapsulating single cells from mammalian cancer cell lines (MCF-7, HepG2, and U937) and microorganisms (Chlorella vulgaris) were successfully exchanged to cell culture media by quick (~10 min) depletion of the surrounding oil phase without coalescence of neighboring microcapsules. Cell proliferation and high integrity of the microcapsules were also demonstrated by long-term incubation of microcapsules containing a single live cell. We expect that this method for the simple and rapid purification of encapsulated single-cell microcapsules will attain widespread adoption, assisting cell biologists and clinicians in the development of single-cell experiments. PMID- 25130500 TI - A Comparison of mucosal surface area and villous histology in small intestines of the Brazilian free-tailed bat (Tadarida brasiliensis) and the mouse (Mus musculus). AB - Studies on birds have led to the hypothesis that increased intestinal absorption between enterocytes (paracellular) evolved as a compensation for smaller intestinal size in fliers, which was perhaps selected to minimize the mass of digesta carried. This hypothesis predicts that bats will also exhibit relatively reduced intestinal size and high paracellular absorption, compared with nonflying mammals. Published studies on three bat species indicate relatively high paracellular absorption. One mechanism for increasing paracellular absorption per cm2 small intestine (SI) is increased number of tight junctions (TJs) across which paracellular absorption occurs. To our knowledge, we provide the first comparative analysis of enterocyte size and number in flying and nonflying mammals. Intestines of insectivorous bats Tadarida brasiliensis were compared with Mus musculus using hematoxylin and eosin staining method. Bats had shorter and narrower SIs than mice, and after correction for body size difference by normalizing to mass3/4, the bats had 40% less nominal surface area than the mouse, as predicted. Villous enhancement of surface area was 90% greater in the bat than in the mouse, mainly because of longer villi and a greater density of villi in bat intestines. Bat and mouse were similar in enterocyte diameter. Bats exceeded mice by 54.4% in villous area per cm length SI and by 95% in number of enterocytes per cm2 of the nominal surface area of the SI. Therefore, an increased density of TJs per cm2 SI may be a mechanistic explanation that helps to understand the high paracellular absorption observed in bats compared to nonflying mammals. PMID- 25130501 TI - Non-local atomic manipulation on semiconductor surfaces in the STM: the case of chlorobenzene on Si(111)-7*7. AB - Control over individual atoms with the scanning tunnelling microscope (STM) holds the tantalising prospect of atomic-scale construction, but is limited by its "one atom at a time" serial nature. "Remote control" through non-local STM manipulation-as we have demonstrated in the case of chlorobenzene on Si(111)-7*7 offers a new avenue for future "bottom-up" nanofabrication, since hundreds of chemical reactions may be carried out in parallel. Thus a good understanding of the non-local manipulation process, as provided by recent experiments, is important. Comparison of scanning tunnelling spectroscopy (STS) measurements of the bare Si(111)-7*7 surface and chemisorbed chlorobenzene molecules with the voltage dependence of the non-local STM-induced desorption of chlorobenzene proves particularly instructive. For example, the chlorobenzene LUMO appears at +0.9 V with respect to the Fermi level, whereas non-local manipulation thresholds are found at +2.1 V and +2.7 V. This difference supports a picture in which the voltage thresholds for non-local electron-induced desorption depend principally on the energies of the electronic states of the surface. Furthermore, the demonstration that the non-local process is largely insensitive to surface steps up to five layers in height suggests that either the electron transport in this process is subsurface in character or surface charge transport is responsible but is in some way unaffected by the steps. PMID- 25130502 TI - Purification of active myrosinase from plants by aqueous two-phase counter current chromatography. AB - INTRODUCTION: Myrosinase (thioglucoside glucohydrolase; E.C. 3.2.1.147), is a plant enzyme of increasing interest and importance to the biomedical community. Myrosinase catalyses the formation of isothiocyanates such as sulforaphane (from broccoli) and 4-(alpha-l-rhamnopyranosyloxy)benzyl isothiocyanate (from moringa), which are potent inducers of the cytoprotective phase-2 response in humans, by hydrolysis of their abundant glucosinolate (beta-thioglucoside N-hydroxysulphate) precursors. OBJECTIVE: To develop an aqueous two-phase counter-current chromatography (CCC) system for the rapid, three-step purification of catalytically active myrosinase. METHODS: A high-concentration potassium phosphate and polyethylene glycol biphasic aqueous two-phase system (ATPS) is used with a newly developed CCC configuration that utilises spiral-wound, flat twisted tubing (with an ovoid cross-section). RESULTS: Making the initial crude plant extract directly in the ATPS and injecting only the lower phase permitted highly selective partitioning of the myrosinase complex before a short chromatography on a spiral disk CCC. Optimum phase retention and separation of myrosinase from other plant proteins afforded a 60-fold purification. CONCLUSION: Catalytically active myrosinase is purified from 3-day broccoli sprouts, 7-day daikon sprouts, mustard seeds and the leaves of field-grown moringa trees, in a CCC system that is predictably scalable. PMID- 25130504 TI - Are cytokeratin-positive cells in sentinel lymph nodes of patients with invasive breast carcinomas up to 5 mm usually insignificant? AB - AIMS: It is known that sentinel lymph nodes (SLN) may be falsely positive due to displaced epithelial cells, particularly in cases with an underlying intraductal papilloma. Given the low metastatic rate in pT1a carcinomas, we aimed to investigate the effect of this phenomenon on staging. METHODS AND RESULTS: Using morphology and immunohistochemistry, we classified the epithelial cells in the SLN in 39 cases of pT1a carcinoma as positive for carcinoma in six, negative in 26 and undetermined in seven. Comparative morphology and immunohistochemistry (using oestrogen receptor, ER) showed complete concordance between the primary carcinoma and SLN in the positive cases, and discordance in the negative cases. The primary tumours in the negative cases were ER-positive except one, in contrast to the SLN cytokeratin-positive (CK(+) ) cells, which were ER-negative. The exception was a case with a Her2-positive primary, in which the SLN CK(+) cells did not stain for Her2. In these cases considered SLN-negative, either displacement (19 cases) or an intraductal papilloma (20 cases) was identified. Two cases showed displacement of benign and malignant cells in the biopsy. Seven cases were indeterminate due to the small number of SLN CK(+) cells, precluding comparison with the primary. CONCLUSION: Given the low rate of metastases in pT1a carcinomas, the significance of SLN CK(+) cells should be resolved by comparative morphology and immunohistochemistry to prevent erroneous upstaging. PMID- 25130503 TI - A high polymerized grass pollen extract is efficacious and safe in a randomized double-blind, placebo-controlled study using a novel up-dosing cluster-protocol. AB - BACKGROUND: Cluster immunotherapy represents an interesting alternative to conventional up-dosing schedules because it allows achieving the maintenance dose within a shorter time interval. In this study, the efficacy and safety of cluster immunotherapy with a high polymerized allergen extract of a grass/rye pollen mixture have been evaluated in a randomized, double-blind, placebo-controlled, multicenter study. METHODS: In total, 121 patients with allergic rhinoconjunctivitis due to grass pollen were randomized 1 : 1 to verum or placebo group. A short cluster up-dosing schedule of only 1 week was applied to achieve the maintenance dose which was administered monthly during the study period of 1 year. Total combined symptom and medication score (TCS) was defined as primary outcome parameter. Secondary outcome parameters were individual symptom and medication scores, 'well days,' global improvement as well as immunological effects and nasal allergen challenge. The safety profile was evaluated based on the European academy of allergy and clinical immunology grading system. RESULTS: Significant reduction in the verum compared to the placebo group (intention-to treat, population, verum: n = 55; placebo: n = 47) was found regarding TCS (P = 0.005), rhinoconjunctivitis total symptom score (RTSS, P = 0.006), and total rescue medication score (TRMS, P = 0.002). Additionally, secondary outcomes such as 'well days,' nasal challenge results, and increase of specific IgG4 were in favor of the active treatment. All systemic adverse reactions (0.8% of all injections in the verum group) were of mild intensity. No severe reactions related to the study medication were observed. CONCLUSION: Cluster immunotherapy with high polymerized grass pollen extracts resulted in significant clinical efficacy and has been shown to be a safe treatment for grass pollen-allergic patients. PMID- 25130505 TI - High prevalence of vitamin D deficiency and insufficiency in adolescent inpatients diagnosed with eating disorders. AB - OBJECTIVE: Previous studies assessing vitamin D status in adolescents with eating disorders showed inconsistent results. The aim of the current study was to assess vitamin D status in a large cohort of adolescent inpatients with eating disorders and its relation to bone mineral density (BMD) and depression. METHOD: 25 Hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline phosphatase levels as well as BMD and depression were assessed on admission in 87 inpatients (aged 16 +/- 2 years, females = 81) with eating disorders [anorexia nervosa (AN) = 64; bulimia nervosa (BN) = 5; eating disorders not otherwise specified-binge/purge type (EDNOS-B/P) = 18]. RESULTS: Mean 25OHD levels were 24.1 +/- 7.5 ng/ml (25.0 +/- 7.6, 25.4 +/- 9.9, and 22.0 +/- 9.9 ng/ml in patients with AB, BN, and EDNOS B/P, respectively). Vitamin D deficiency (<15 ng/ml) was found in 7.8% of the patients, and insufficiency (15-20 ng/ml) in 22.2%. Only 16.7% had levels >32 ng/ml, considered optimal by some experts. No associations were found between 25OHD levels and BMD or comorbid depression. 25OHD levels during winter were significantly lower than summer levels (p < .001). Mean lumbar spine BMD z-score in patients with AN and EDNOS-B/P type was low (-1.5 +/- 1.1) and correlated with body mass index standard deviation score (p = .03). DISCUSSION: Adolescents with eating disorders show a high prevalence of vitamin D deficiency and insufficiency. Given the risk of osteoporosis in this population, 25OHD levels found in this group may not offer optimal bone protection. Vitamin D levels should be routinely checked and supplementation should be administered as required. PMID- 25130506 TI - Rethinking nasal tip support: a finite element analysis. AB - OBJECTIVE: We employ a nasal tip finite element model (FEM) to evaluate contributions of two of the three major tip support mechanisms: attachments between the upper and lower lateral cartilages and attachment of the medial crura to the caudal septum. STUDY DESIGN: The nasal tip FEM computed stress distribution and strain energy density (SED) during nasal tip compression. We examined the impact of attachments between the upper and lower lateral cartilages and the attachment of the medial crura to the caudal septum on nasal tip support. METHODS: The FEM consisted of three tissue components: bone, cartilage, and skin. Four models were created: A) control model with attachments present at the scroll and caudal septum; B) simulated disruption of scroll; C) simulated disruption of medial crura attachments to caudal septum; and D) simulated disruption of scroll and medial crura attachments to caudal septum. Spatial distribution of stress and SED were calculated. RESULTS: The keystone, intermediate crura, caudal septum, and nasal spine demonstrated high concentration of stress distribution. Across all models, there was no difference in stress distribution. Disruption of the scroll resulted in 1% decrease in SED. Disruption of the medial crura attachments to the caudal septum resulted in 4.2% reduction in SED. Disruption of both scroll and medial crural attachments resulted in 9.1% reduction in SED. CONCLUSION: The nasal tip FEM is an evolving tool to study structural nasal tip dynamics and demonstrates the loss of nasal tip support with disruption of attachments at the scroll and nasal base. LEVEL OF EVIDENCE: N/A. PMID- 25130507 TI - Ivermectin: panacea for resource-poor communities? AB - The 2014 Gairdner Global Health Award was conferred for discovery of the unique microorganism that is the sole source of the endectocidal avermectins, and the Public sector/Private sector Partnership that developed innovative biopharmaceuticals with immeasurably beneficial impact on public health worldwide. Ivermectin is already labelled a 'wonder drug', essential for campaigns to eliminate two disfiguring and devastating tropical diseases. New uses for it are identified regularly, including possible antibacterial, antiviral, and anticancer potential. Hundreds of millions of people are taking ivermectin to combat various diseases and afflictions, and mass administration of ivermectin in polyparasitised poor communities around the world is increasingly recognised as a mechanism to easily and cost-effectively improve overall health and quality of life for everyone. PMID- 25130508 TI - Impact of body mass index on outcomes of laparoscopic radical prostatectomy with long-term follow-up. AB - OBJECTIVE: The aim of this study was to investigate the impact of body mass index (BMI) on the functional and oncological results of patients who had undergone laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS: In total, 1224 patients with follow-up data (>24 months) were enrolled. Patients were divided into three groups according to BMI (kg/m(2)) as: group 1 (normal, BMI <25, n = 425), group 2 (overweight, 25 <= BMI <30, n = 594) and group 3 (obese, BMI >= 30, n = 205). Demographic, intraoperative and postoperative data with oncological outcomes were recorded. The impact of obesity on those parameters was evaluated and statistical analyses were performed. RESULTS: Mean age was 63.8 +/- 6.1 years and mean follow-up was 43.1 +/- 25.1 months (mean +/- SD). There were 425 (34.7%) patients in group 1, 594 (48.5%) in group 2 and 205 (16.8%) in group 3. Operation time, clinical stage and estimated blood loss were significantly higher in group 3 than in the other groups (p < 0.001, p = 0.001 and p = 0.001, respectively). Bilateral nerve-sparing rate and bladder neck-sparing rate were significantly decreased in group 3 compared with the other groups (p = 0.001 and p < 0.038, respectively). Statistically significantly higher pathological stage, tumour volume, positive surgical margin and Gleason scores were determined in group 3 compared with the other groups (p = 0.023, p = 0.018, p = 0.009 and p = 0.028, respectively). There were similar urinary continence rates among the groups. The rate of penetration with or without medication was significantly lower in group 3 than in the other groups (p = 0.593 and p = 0.007, respectively). CONCLUSIONS: LRP seemed safe and effective in obese patients, with similar mean overall survival, cancer-specific survival, complication rates and continence rates to normal weight patients in the long term. PMID- 25130510 TI - Diagnosis and management of atrial fibrillation: an overview. AB - Atrial fibrillation (AF) has been defined as the new cardiovascular "epidemic". Its prevalence is rising in developed countries, and the associated social and economic costs are high. In the last few years, there has been an increasing interest in understanding the mechanisms of AF and its management. New pharmacotherapies together with novel techniques for surgical and catheter treatment of AF have been developed, allowing the maintenance of sinus rhythm and the alleviation of symptoms in a large number of patients with AF. However, there are still some challenges that need to be addressed. This article gives an overview of the current state of the art on novel techniques for diagnosis and management of AF. PMID- 25130511 TI - Detecting human cytomegalovirus drug resistant mutations and monitoring the emergence of resistant strains using real-time PCR. AB - BACKGROUND: Antiviral resistance development is a serious complication of human cytomegalovirus virostatic therapy caused by mutations in UL 97 and/or UL54 genes. OBJECTIVES: To determinate the presence of sensitive and resistant strains in patients developing antiviral resistance. STUDY DESIGN: We used three different molecular biological methods for mutation analysis-restriction fragment length polymorphism, sequencing and real-time PCR approach. RESULTS: We describe three allogeneic hematopoietic stem cell transplant patients developing the GCV resistant HCMV strains manifested by virostatic treatment failure. In these patients we identified UL97 mutations L595S, A594V and A594T and monitored the dynamics of coexisted sensitive/resistant strains. We confirmed the presence of mixed HCMV populations and in two patients a phenomenon of sensitive strain repopulation which occurred after 6.5 months and 1 month after removing GCV pressure. CONCLUSIONS: Our results show changes in proportions of sensitive/resistant subpopulations over time but other studies would be required to demonstrate the beneficial impact of their monitoring on clinical outcome. PMID- 25130509 TI - CHARMM-GUI Membrane Builder toward realistic biological membrane simulations. AB - CHARMM-GUI Membrane Builder, http://www.charmm-gui.org/input/membrane, is a web based user interface designed to interactively build all-atom protein/membrane or membrane-only systems for molecular dynamics simulations through an automated optimized process. In this work, we describe the new features and major improvements in Membrane Builder that allow users to robustly build realistic biological membrane systems, including (1) addition of new lipid types, such as phosphoinositides, cardiolipin (CL), sphingolipids, bacterial lipids, and ergosterol, yielding more than 180 lipid types, (2) enhanced building procedure for lipid packing around protein, (3) reliable algorithm to detect lipid tail penetration to ring structures and protein surface, (4) distance-based algorithm for faster initial ion displacement, (5) CHARMM inputs for P21 image transformation, and (6) NAMD equilibration and production inputs. The robustness of these new features is illustrated by building and simulating a membrane model of the polar and septal regions of E. coli membrane, which contains five lipid types: CL lipids with two types of acyl chains and phosphatidylethanolamine lipids with three types of acyl chains. It is our hope that CHARMM-GUI Membrane Builder becomes a useful tool for simulation studies to better understand the structure and dynamics of proteins and lipids in realistic biological membrane environments. PMID- 25130513 TI - Urodynamic testing: physiological background, setting-up, calibration and artefacts. AB - Urodynamics (UDS) is an interactive diagnostic study of lower urinary tract function. It is composed of several tests that can be used to obtain functional information about urine storage and expulsion. Its main goal is to reproduce the patients' symptoms and determine their cause. The present article is a review of the physiological concepts behind UDS, and explains the various normal and abnormal forces and parameters that are measured and used during the tests to assist the physician in making a diagnosis. It outlines the importance and methods of the calibration of UDS equipment to optimise diagnostic accuracy and reliability, which would have a crucial impact over the treatment's decision, and consequently the patient's outcome. PMID- 25130512 TI - IFNL4 polymorphism predicts response to hepatitis C treatment after liver transplantation. AB - BACKGROUND: Recent studies in chronic hepatitis C patients have shown that rs368234815 polymorphism nearby IL28B is a better predictor of response to antiviral treatment with pegylated interferon and ribavirin than IL28B polymorphisms (rs12979860 and rs8099917). Its effect could be related to interferon lambda 4 (IFNL4), a protein which seems to confer some paradoxical disadvantages in hepatitis C virus (HCV) immune response. OBJECTIVES: To assess the role of IFNL4 rs368234815 polymorphism on the response to antiviral treatment after liver transplantation (LT). STUDY DESIGN: IFNL4 and IL28B polymorphisms were genotyped in 86 HCV-infected LT recipients and in their donors; all patients had undergone antiviral treatment with pegylated interferon and ribavirin after LT. RESULTS: IFNL4 polymorphism strongly correlated with IL28B ones (p < 0.001). The favorable IFNL4 genotype (TT/TT) was significantly more frequent among donors than recipients (60% donors vs. 22% recipients, p <0.001). Recipient TT/TT genotype was associated with a higher sustained virological response rate after LT (p = 0.024). Nevertheless, the highest sustained virological response frequency was found when both donors and recipients had favorable genotypes (73% vs. 25%, p = 0.002), suggesting a role for donor genotype. CONCLUSIONS: Our study demonstrates that IFNL4 rs368234815 polymorphism is an important predictor of response to antiviral treatment in the LT setting. These findings warrant further studies on IFNL4 role in immune response against HCV. PMID- 25130515 TI - Bariatric surgery in the elderly: 2009-2013. AB - BACKGROUND: Ample evidence supports the safety and effectiveness of bariatric surgery in the general adult population but more information is needed in patients age 60 years and older (elderly). We previously examined the outcome of bariatric surgery performed in the elderly between 1999 and 2005 using the University HealthSystem Consortium (UHC) Clinical Database. The aim of this study was to analyze contemporary outcomes of bariatric surgery in the elderly and to compare them to previous data from 1999-2005. METHODS: Using International Classification of Diseases, 9(th) Revision diagnosis and procedure codes, we obtained data from the UHC database for all elderly (age >60 yr) and adult nonelderly (age 19-60 yr) patients who underwent bariatric surgery for the treatment of morbid obesity between 2009 and 2013. Outcome measures, such as patient characteristics, LOS, morbidity, and observed-to-expected (risk-adjusted) mortality ratio were compared between elderly and nonelderly patients. RESULTS: Bariatric surgery in the elderly made up 2.7% of all bariatric operations in 1999 2005. This represents an increase to 10.1% of all bariatric operations in 2009 2013. In-hospital mortality was .30% for the nonelderly and .70% for the elderly in 1999-2005, whereas contemporary in-hospital mortality has decreased to .11% for the nonelderly and .05% for the elderly. CONCLUSION: Our results show that the number of bariatric procedures performed in the elderly is increasing and now represents 10% of all bariatric operations performed at academic centers. In hospital mortality in bariatric surgery in the elderly has improved so much that it is now even better than in-hospital mortality in the nonelderly in 1999-2005. PMID- 25130514 TI - TNF-alpha-induced cardiomyocyte apoptosis contributes to cardiac dysfunction after coronary microembolization in mini-pigs. AB - This experimental study was designed to clarify the relationship between cardiomyocyte apoptosis and tumour necrosis factor-alpha (TNF-alpha) expression, and confirm the effect of TNF-alpha on cardiac dysfunction after coronary microembolization (CME) in mini-pigs. Nineteen mini-pigs were divided into three groups: sham-operation group (n = 5), CME group (n = 7) and adalimumab pre treatment group (n = 7; TNF-alpha antibody, 2 mg/kg intracoronary injection before CME). Magnetic resonance imaging (3.0-T) was performed at baseline, 6th hour and 1 week after procedure. Cardiomyocyte apoptosis was detected by cardiac TUNEL staining, and caspase-3 and caspase-8 were detected by RT-PCR and immunohistochemistry. Furthermore, serum TNF-alpha, IL-6 and troponin T were analysed, while myocardial expressions of TNF-alpha and IL-6 were detected. Both TNF-alpha expression (serum level and myocardial expression) and average number of apoptotic cardiomyocyte nuclei were significantly increased in CME group compared with the sham-operation group. Six hours after CME, left ventricular end systolic volume (LVESV) was increased and the left ventricular ejection fraction (LVEF) was decreased in CME group. Pre-treatment with adalimumab not only significantly improved LVEF after CME (6th hour: 54.9 +/- 2.3% versus 50.4 +/- 3.9%, P = 0.036; 1 week: 56.7 +/- 4.2% versus 52.7 +/- 2.9%, P = 0.041), but also suppressed cardiomyocyte apoptosis and the expression of caspase-3 and caspase-8. Meanwhile, the average number of apoptotic cardiomyocytes nuclei was inversely correlated with LVEF (r = -0.535, P = 0.022). TNF-alpha-induced cardiomyocyte apoptosis is likely involved in cardiac dysfunction after CME. TNF-alpha antibody therapy suppresses cardiomyocyte apoptosis and improves early cardiac function after CME. PMID- 25130516 TI - Mesenteric venous thrombosis following vertical sleeve gastrectomy in an adolescent. PMID- 25130517 TI - Comment on: POSSUM and p-POSSUM overestimate morbidity and mortality in laparoscopic bariatric surgery. PMID- 25130519 TI - CD8+ tumour-infiltrating lymphocytes and COX2 expression may predict relapse in differentiated thyroid cancer. AB - BACKGROUND/OBJECTIVE: There is an increasing rate of papillary thyroid carcinomas that may never progress to cause symptoms or death. Predicting outcome and determining tumour aggressiveness could help diminish the number of patients submitted to aggressive treatments. We aimed to evaluate whether markers of the immune system response and of tumour-associated inflammation could predict outcome of differentiated thyroid cancer (DTC) patients. DESIGN: Retrospective cohort study. PATIENTS: We studied 399 consecutive patients, including 325 papillary and 74 follicular thyroid carcinomas. MEASUREMENTS: Immune cell markers were evaluated using immunohistochemistry, including tumour-associated macrophages (CD68) and subsets of tumour-infiltrating lymphocytes (TIL), such as CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also investigated the expression of cyclooxygenase 2 (COX2) in tumour cells and the presence of concurrent lymphocytic infiltration characterizing chronic thyroiditis. RESULTS: Concurrent lymphocytic infiltration characterizing chronic thyroiditis was observed in 29% of the cases. Among all the immunological parameters evaluated, only the enrichment of CD8+ lymphocytes (P = 0.001) and expression of COX2 (P =0.01) were associated with recurrence. A multivariate model analysis identified CD8+ TIL/COX2 as independent risk factor for recurrence. A multivariate analysis using Cox's proportional-hazards model adjusted for the presence of concurrent chronic thyroiditis demonstrated that the presence of concurrent chronic thyroiditis had no effect on prognostic prediction mediated by CD8+ TIL and COX2. CONCLUSION: In conclusion, we suggest the use of a relatively simple pathology tool to help select cases that may benefit of a more aggressive approach sparing the majority of patients from unnecessary procedures. PMID- 25130520 TI - Impulsivity, risk-taking, and distractibility in rats exhibiting robust conditioned orienting behaviors. AB - When a neutral cue is followed by a significant event such as food delivery, some animals become engaged with the cue itself and acquire cue-directed behaviors. One type of cue-directed behavior is observed following insertion of a lever used as a conditioned stimulus (CS). Rats showing robust approach behavior to the lever also display impulsivity and altered attention, as compared to rats showing behavior directed toward the reward delivery location. The current study used a light CS to categorize rats' propensity for cue-directed behavior, and assessed whether individual differences in impulsivity and related behaviors still emerged. During the light-food pairings, some rats displayed enhanced rearing or orienting to the light (Orienters) prior to showing food cup approach behavior, while other rats only showed food cup approach behavior (Nonorienters). Our results showed that Orienters made more impulsive and risky decisions in two different choice tasks, and were quicker to leave a familiar dark environment to enter a novel bright field. Orienters also showed less accurate target detection when a visual distractor was introduced during an attentional challenge. Our current study suggests that light CS-induced rearing/orienting behavior might not necessarily share an identical mechanism with lever CS-approach behavior in predicting impulsivity-related behaviors. PMID- 25130518 TI - Cost effectiveness of telecare management for pain and depression in patients with cancer: results from a randomized trial. AB - OBJECTIVE: Pain and depression are prevalent and treatable symptoms among patients with cancer, yet they are often undetected and undertreated. The Indiana Cancer Pain and Depression (INCPAD) trial demonstrated that telecare management can improve pain and depression outcomes. This article investigates the incremental cost effectiveness of the INCPAD intervention. METHODS: The INCPAD trial was conducted in 16 community-based urban and rural oncology practices in Indiana. Of the 405 participants, 202 were randomized to the intervention group and 203 to the usual-care group. Intervention costs were determined, and effectiveness outcomes were depression-free days and quality-adjusted life years. RESULTS: The intervention group was associated with a yearly increase of 60.3 depression-free days (S.E. = 15.4; P < 0.01) and an increase of between 0.033 and 0.066 quality-adjusted life years compared to the usual care group. Total cost of the intervention per patient was US$1189, which included physician, nurse care manager and automated monitoring set-up and maintenance costs. Incremental cost per depression-free day was US$19.72, which yields a range of US$18,018 to US$36,035 per quality-adjusted life year when converted to that metric. When measured directly, the incremental cost per quality-adjusted life year ranged from US$10,826 based on the modified EQ-5D to US$73,286.92 based on the SF-12. CONCLUSION: Centralized telecare management, coupled with automated symptom monitoring, appears to be a cost effective intervention for managing pain and depression in cancer patients. PMID- 25130522 TI - Anterior guidance--movement and stability. AB - Instability of our orthodontic treatment is not uncommon, in particular in the anterior teeth. Given that the mandible is constantly in movement and that the lower and upper teeth regularly meet head-on during normal functioning, one might ask: are the static and normative end of treatment objectives we generally target sufficient to ensure treatment stability? PMID- 25130524 TI - Between a rock and a hard place: getting families to change behaviors to reduce pediatric stone disease recurrence. PMID- 25130525 TI - Transobturator versus retropubic approach for a mid urethral sling. PMID- 25130523 TI - A lower intensity of treatment may underlie the increased risk of thrombosis in young patients with masked polycythaemia vera. AB - In patients who do not meet the World Health Organization (WHO) criteria for overt polycythaemia vera (PV), a diagnosis of masked PV (mPV) can be determined. A fraction of mPV patients may display thrombocytosis, thus mimicking essential thrombocythaemia (ET). No previous studies have examined clinical outcomes of mPV among young JAK2-mutated patients. We analysed a retrospective cohort of 538 JAK2 mutated patients younger than 40 years, after a re-assessment of the diagnosis according to the haemoglobin threshold for mPV. In this cohort of patients, 97 (18%) met the WHO criteria for PV, 66 patients (12%) were classified as mPV and 375 (70%) as JAK2-mutated ET. Surprisingly, a significant difference in the incidence of thrombosis was found when comparing mPV versus overt PV patients (P = 0.04). In multivariate analysis, the only factor accounting for the difference in the risk of thrombosis was the less frequent use of phlebotomies and cytoreduction in mPV patients compared to those with overt PV. Thus, we emphasize the need for the identification of mPV in young JAK2-mutated patients in order to optimize their treatments. PMID- 25130528 TI - Editorial comment. PMID- 25130529 TI - Outcomes of retroperitoneal lymph node dissection for the most challenging cases. PMID- 25130530 TI - Epigenetic factors affect tumor initiation, progression and recurrence. PMID- 25130531 TI - Complications of stone disease in the 21st century--can noninvasive and minimally invasive treatment modalities improve the overall renal health of stone formers? PMID- 25130532 TI - Water nanodroplets make a greater contribution to facial skin moisture levels in air-conditioned rooms during winter than in summer. AB - BACKGROUND/PURPOSE: By performing experiments in air-conditioned chamber, we previously demonstrated that the presence of water nanodroplets (mist) improved facial skin moisture levels without reducing water loss from the facial skin surface or inducing excessive humidity. Some previous studies have demonstrated that the epidermis is a less effective barrier to water in winter because the corneocytes that comprise facial skin become smaller in winter as skin turnover increases in cold environments. We hypothesized that it would be easier for mist to penetrate into the facial stratum corneum (SC) in winter than in summer. In the present study, we investigated the ability of mist to improve facial skin moisture levels in winter and summer. METHODS: We examined transepidermal water loss (TEWL) as an index of barrier function and skin conductance as an index of SC hydration at the forehead, lateral canthus, and cheeks in eight healthy Japanese females (mean +/- SD: 45.5 +/- 3.2 years) in the presence or absence of mist in February-March and July. RESULTS: In the absence of mist, skin conductance at the forehead and lateral canthus was significantly higher in summer than in winter, but these seasonal differences were diminished in the presence of mist. In the presence of mist, skin conductance was increased in winter and decreased in summer at the lateral canthus; however, these changes were not significant. Thus, our findings suggest that mist penetrates into the SC and improves skin moisture levels in winter. CONCLUSION: We demonstrated that it is easier for mist to penetrate into the SC at the lateral canthus during winter than in summer. Thus, mist is expected to improve facial moisture levels in winter by penetrating into and remaining in the SC. Hence, mist could be used to help prevent facial skin from becoming dry in air-conditioned rooms during winter. PMID- 25130534 TI - Inpatient pharmacological sleep aid utilization is common at a tertiary medical center. AB - BACKGROUND: Sleep is known to be poor in the hospital. Patients frequently request pharmacological sleep aids, despite the risk of altered mental status (delirium) and falls. Little is known about the scope of pharmacological sleep aid use in hospitalized patients. METHODS: We performed a single center, retrospective review of all patients admitted to the general adult (age >18 years) medical and surgical units of a tertiary care center during a recent 2 month period (January 2013-February 2013). Review of the electronic medication administration system was performed to assess for medications administered for sleep. RESULTS: Of 642 unique admissions, 168 patients (26.2%) received a medication for sleep. Most (n = 115, 68.5%) had no known history of insomnia or regular prior sleep medication use. Patients most frequently were treated with trazodone (30.4%; median dose, 50 mg; range, 12.5-450 mg), lorazepam (24.4%; median, 0.5 mg; range, 0.25-2 mg), and zolpidem tartrate (17.9%; median, 10 mg; range, 2.5-10 mg). Of the medications given, 36.7% were given early (before 9 pm) or late (after midnight). Of patients not known to be previously taking a pharmacological sleep aid, 34.3% of them were discharged with a prescription for one. CONCLUSIONS: Despite increasing evidence of risks such as delirium or falls, pharmacological sleep aid use in general wards remains common, even in elderly patients. Medication administration time is frequently suboptimal. Many previously sleep medication-naive patients leave the hospital with a sleep aid prescription. Further research is needed to understand the factors that contribute to the high rate of sleep medication use in hospitalized patients. PMID- 25130536 TI - Curcumin attenuates Cr(VI)-induced ascites and changes in the activity of aconitase and F(1)F(0) ATPase and the ATP content in rat liver mitochondria. AB - Occupational and environmental exposure to potassium dichromate (K2Cr2O7), a hexavalent chromium compound, can result in liver damage associated with oxidative stress and mitochondrial dysfunction. The purpose of this study was to evaluate the effect of the antioxidant curcumin (400 mg/kg b.w.) on the K2Cr2O7 induced injury, with special emphasis on ascitic fluid accumulation and oxidative phosphorylation mitochondrial enzymes and the adenosine triphosphate (ATP) levels in isolated mitochondria from livers of rats treated with K2Cr2O7 (15 mg/kg b.w.). Thus, curcumin attenuated the ascites generation, prevented the decrease in the activities of aconitase and F1F0 ATPase, and maintained the ATP levels. The activity of complex II was not completely reestablished by curcumin, whereas complexes III and IV activities were unchanged. PMID- 25130535 TI - Nutrient intakes associated with elevated serum C-reactive protein concentrations in normal to underweight breastfeeding women in Northern Kenya. AB - OBJECTIVES: Low-grade elevation of C-reactive protein (CRP) is a non-specific inflammatory marker, used as a predictor for cardiovascular disease development and chronic inflammatory risks. Research investigating dietary influences on inflammation has focused primarily on the relationship between dietary characteristics, CRP elevation and BMI in the populations at greatest risk for cardiovascular disease, namely those in the overweight and obese ranges, often in clinical settings and/or among those middle aged or older, leaving little information about normal to underweight populations of reproductive age in ecological settings. This study evaluates impacts of dietary nutrients on serum CRP levels in a population of predominantly underweight to normal weight adult women experiencing the additional nutritional demands of lactation. METHODS: Data from non-overweight breastfeeding Ariaal women of Kenya collected in 2006 were used (n = 194). Logistic regression models were applied using low-grade CRP elevation (hsCRP > 3 mg/L) as the outcome variable and dietary nutrients, age, BMI, and serum retinol as predictors. RESULTS: Models showed that energy intake (Kcal) and age were positive predictors of CRP elevation while folate intake, total vitamin A intake, and serum retinol concentration were protective against CRP elevation. Unlike previous studies among higher BMI populations, this study found no significant effect of dietary lipids/fatty acids or BMI on CRP elevation. CONCLUSIONS: The effects of specific dietary nutrients on inflammatory status may vary with BMI or, in women, reproductive status. Further research should investigate the role of dietary fats, fatty acids, and antioxidant vitamins across populations with a wide range of BMI, including postpartum women. PMID- 25130533 TI - Epigenetic mechanisms of memory formation and reconsolidation. AB - Memory consolidation involves transcriptional control of genes in neurons to stabilize a newly formed memory. Following retrieval, a once consolidated memory destabilizes and again requires gene transcription changes in order to restabilize, a process referred to as reconsolidation. Understanding the molecular mechanisms of gene transcription during the consolidation and reconsolidation processes could provide crucial insights into normal memory formation and memory dysfunction associated with psychiatric disorders. In the past decade, modifications of epigenetic markers such as DNA methylation and posttranslational modifications of histone proteins have emerged as critical transcriptional regulators of gene expression during initial memory formation and after retrieval. In light of the rapidly growing literature in this exciting area of research, we here examine the most recent and latest evidence demonstrating how memory acquisition and retrieval trigger epigenetic changes during the consolidation and reconsolidation phases to impact behavior. In particular we focus on the reconsolidation process, where we discuss the already identified epigenetic regulators of gene transcription during memory reconsolidation, while exploring other potential epigenetic modifications that may also be involved, and expand on how these epigenetic modifications may be precisely and temporally controlled by important signaling cascades critical to the reconsolidation process. Finally, we explore the possibility that epigenetic mechanisms may serve to regulate a system or circuit level reconsolidation process and may be involved in retrieval-dependent memory updating. Hence, we propose that epigenetic mechanisms coordinate changes in neuronal gene transcription, not only during the initial memory consolidation phase, but are triggered by retrieval to regulate molecular and cellular processes during memory reconsolidation. PMID- 25130538 TI - Bioreducible branched polyethyleneimine derivatives physically loaded with hydrophobic pheophorbide A: preparation, characterization, and light-induced cytotoxicity. AB - Branched-type hydrophilic polyethyleneimine derivatives (i.e., bPEI derivatives) are developed polymeric carriers for photodynamic therapy. Their chemical structures which contain pH-tunable hydrophobic/hydrophilic cavities enable efficient loading of hydrophobic drugs in basic pH environments. Intracellular stimuli trigger the release of the loaded drugs in bPEI derivatives. As expected, the hydrophobic photosensitizer known as pheophorbide A (PheoA) is solubilized by physical loading in the inner hydrophobic spaces of bPEI derivatives in environments with basic pH values. Interestingly, acidic pH environments induce aggregation, resulting in poor release of the loaded PheoA as well as in quenched photo-activity of the PheoA-loaded polymers. However, when reducible polycation derivatives of bPEI are used (i.e., RPC-bPEI), intracellular thiols degrade the disulfide linkages in the polymers, resulting in rapid PheoA release. Particularly, a RPC-bPEI containing 6 wt% PheoA (i.e., RPC-bPEI(0.8 kDa) PheoA(6%)) respond remarkably well to light exposure and display large differences between dark toxicity and light-induced toxicity. Cellular uptake of RPC-bPEI(0.8 kDa)-PheoA(6%) is approximately sevenfold to ninefold lower than that of free PheoA. Nevertheless, the photo-toxicity of RPC-bPEI(0.8 kDa) PheoA(6%) was only two- to sixfold less potent than that of free PheoA. These results suggest that reducible bPEI materials may act as potential solubilizers and carriers for low-molecular-weight hydrophobic anti-cancer drugs. PMID- 25130537 TI - The PAX2-null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium. AB - The oviducts contain high-grade serous cancer (HGSC) precursors (serous tubal intraepithelial neoplasia or STINs), which are gamma-H2AX(p) - and TP53 mutation positive. Although they express wild-type p53, secretory cell outgrowths (SCOUTs) are associated with older age and serous cancer; moreover, both STINs and SCOUTs share a loss of PAX2 expression (PAX2(n) ). We evaluated PAX2 expression in proliferating adult and embryonic oviductal cells, normal mucosa, SCOUTs, Walthard cell nests (WCNs), STINs, and HGSCs, and the expression of genes chosen empirically or from SCOUT expression arrays. Clones generated in vitro from embryonic gynaecological tract and adult Fallopian tube were Krt7(p) /PAX2(n) /EZH2(p) and underwent ciliated (PAX2(n) /EZH2(n) /FOXJ1(p) ) and basal (Krt7(n) /EZH2(n) /Krt5(p) ) differentiation. Similarly, non-ciliated cells in normal mucosa were PAX2(p) but became PAX2(n) in multi-layered epithelium undergoing ciliated or basal (WCN) cell differentiation. PAX2(n) SCOUTs fell into two groups: type 1 were secretory or secretory/ciliated with a 'tubal' phenotype and were ALDH1(n) and beta-catenin(mem) (membraneous only). Type 2 displayed a columnar to pseudostratified (endometrioid) phenotype, with an EZH2(p) , ALDH1(p) , beta-catenin(nc) (nuclear and cytoplasmic), stathmin(p) , LEF1(p) , RCN1(p) , and RUNX2(p) expression signature. STINs and HGSCs shared the type 1 immunophenotype of PAX2(n) , ALDH1(n) , beta-catenin(mem) , but highly expressed EZH2(p) , LEF1(p) , RCN1(p) , and stathmin(p) . This study, for the first time, links PAX2(n) with proliferating fetal and adult oviductal cells undergoing basal and ciliated differentiation and shows that this expression state is maintained in SCOUTs, STINs, and HGSCs. All three entities can demonstrate a consistent perturbation of genes involved in potential tumour suppressor gene silencing (EZH2), transcriptional regulation (LEF1), regulation of differentiation (RUNX2), calcium binding (RCN1), and oncogenesis (stathmin). This shared expression signature between benign and neoplastic entities links normal progenitor cell expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a common pathway that could be a target for early prevention. PMID- 25130539 TI - Parenteral administration of GnRH constructs and adjuvants: immune responses and effects on reproductive tissues of male mice. AB - Two gonadotrophin releasing hormone (GnRH) constructs prepared by either chemical conjugation to keyhole limpet hemocyanin (GnRH-KLH) or as an expressed recombinant fusion protein (Multimer) were evaluated with or without adjuvants (immunostimulating complexes, ISCOMs, or cytosine-phosphate-guanosine oligodeoxynucleotides, CpG ODNs). After subcutaneous administration to Balb/c male mice at Weeks 0, 2 and 4, these preparations were assessed for induction of immune responses and effects on reproductive organs. GnRH-KLH plus ISCOMs formulation induced strong IgG immune responses from Week 4 through Week 12 resulting in consistent reproductive organ atrophy by Week 12 after subcutaneous administration. GnRH-KLH plus CpG ODNs generated immune responses but no atrophy of reproductive tissues by Week 12. Multimer plus ISCOMs induced poor immune responses and no effects on reproductive tissues by Week 12. In the absence of additional adjuvant, none of the GnRH constructs induced reproductive organ atrophy. GnRH-KLH induced stronger immune responses when formulated with ISCOMs or CpG ODN compared to Multimer. GnRH-KLH with ISCOMs could be an effective colloidal alternative for emulsion GnRH vaccine formulations. PMID- 25130540 TI - Complete protection against lethal challenge of novel H7N9 virus with heterologous inactivated H7 vaccine in mice. AB - A prototype H7 influenza vaccine constructed based on the H7N7 outbreak in 2003 was tested for the protective efficacy against the novel H7N9 virus in a lethal murine challenge model. Serum samples from vaccinated mice showed significant neutralizing activity against the H7N9 virus and the mice were completely protected with no significant weight loss. The results have direct implications on how to overcome potential vaccine shortage and identify donors for immune sera for passive immunization. PMID- 25130541 TI - Mesochanneled hierarchically porous aluminosiloxane aerogel microspheres as a stable support for pH-responsive controlled drug release. AB - The molecular-scale self-assembly of a 3D aluminosiloxane (Al-O-Si) hybrid gel network was successfully performed via the cocondensation of hydrolyzed alumina (AlOOH) and (3-aminopropyl)trimethoxysilane (APS). It was transformed into a microspherical aerogel framework of Al-O-Si containing mesochannels with tunable hierarchically bimodal meso/macroporosities by a subcritical drying technique. Good homogeneity of AlOOH and APS brought during the synthesis guaranteed a uniform distribution of two metal oxides in a single body. A systematic characterization of the aerogel support was carried out using FTIR, SEM, TEM, nitrogen adsorption/desorption analysis, WAXS, SAXS, and xi-potential measurement in order to explore the material for drug uptake and release. The drug loading and release capacity and chemical stability of an aluminosiloxane aerogel were studied using two nonsteroidal antiinflammatory drugs, ibuprofen and aspirin. A comprehensive evaluation of the aluminosiloxane aerogel with ordered mesoporous MCM-41 was also performed. Aerogel supports showed a high drug loading capacity and a pH-responsive controlled-release property compared to MCM-41. Meanwhile, kinetic modeling studies indicate that the drug releases with a zero-order profile following the Korsmeyer-Peppas model. The biocompatibility of aluminosiloxane aerogels was established via ex vivo and in vivo studies. We also outline the use of aluminosiloxane aerogel as a support for a possible 3D matrix for an osteoconductive structure for bone tissue engineering. PMID- 25130542 TI - Proteomic Profiling of Invasive Ductal Carcinoma (IDC) using Magnetic Beads-based Serum Fractionation and MALDI-TOF MS. AB - AIM: To reveal the serum proteomic profiling of intraductal carcinoma (IDC) patients in China, establish a serum proteome fractionation technique for choosing magnetic beads for proteomic analysis in breast cancer research; and identify differentially expressed peptides (m/z; P < 0.0001) as potential biomarkers of early IDCs. METHODS: We used two different kinds of magnetic beads (magnetic bead-based weak cation exchange chromatography (MB-WCX) and immobilized metal ion affinity chromatography (MB-IMAC-Cu)) to analyze 32 patients with early stage (stages I-II) IDC and 32 healthy control serum samples for proteomic profiling by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The mass spectra, analyzed using ClinProTools software, distinguished between IDC patients and healthy individuals based on k-nearest neighbor genetic algorithm. RESULTS: The serum samples purified in the MB-WCX group provided better proteomic patterns than the MB-IMAC Cu group. The samples purified by MB-WCX had better average peak numbers, higher peak intensities, and better capturing ability of low abundance proteins or peptides in serum samples. In addition, the MB-WCX and MB-IMAC-Cu purification methods, followed MALDI-TOF MS identification and use of ClinProTools software accurately distinguished patients with early stage IDC from healthy individuals. CONCLUSION: Serum proteomic profiling by MALDI-TOF MS is a novel potential tool for the clinical diagnosis of patients with IDC in China. PMID- 25130543 TI - The vertebrate corneal epithelium: from early specification to constant renewal. AB - BACKGROUND: The cornea is an ectodermal/neural crest derivative formed through a cascade of molecular mechanisms to give rise to the specific optical features necessary for its refractory function. Moreover, during cornea formation and maturation, epithelial stem cells are sequestered to ensure a constant source for renewal in the adult. RESULTS: Recent progress in the molecular and stem cell biology of corneal morphogenesis and renewal shows that it can serves as a paradigm for epithelial /mesenchymal organ biology. This review will synthesize historical knowledge together with recent data to present a consistent overview of cornea specification, formation, maturation, and maintenance. CONCLUSIONS: This should be of interest not only to developmental biologists but also ophthalmologists, as several human vision problems are known to be rooted in defects in corneal development. PMID- 25130545 TI - The disintegrin and metalloproteinase ADAM10 mediates a canonical Notch-dependent regulation of IL-6 through Dll4 in human endothelial cells. AB - Although the involvement of the disintegrin and metalloproteinase ADAM10 in several areas of vascular biology is now clearly established, its role in vascular inflammation and in Notch signaling at the endothelial level remains unclear. In this study, we demonstrated that ADAM10 specifically localizes in the CD31(+) endothelial cells (ECs) in normal human cardiac tissues and in cultured primary arterial ECs. In vitro, ADAM10 drives a specific regulation of the Notch pathway in vascular ECs. Using an ADAM10 gain and loss of function approach we show an ADAM10-dependent regulation of Dll1 and Dll4 expression in association with changes in Hes1 and Hey1 expression. We also identified IL-6, IL-8, MCP-1 and sVCAM-1 as novel targets of ADAM10 upon inflammation. Although Notch pathway does not seem to be required for the production of IL-8, MCP-1 and sVCAM-1, the release of IL-6 by ECs occurred through ADAM10 and a canonical Notch signaling pathway, dependent of gamma-secretase activity. Moreover, sustained expression of Dll4 mediated by ADAM10 elicits an increased release of IL-6 suggesting a strong implication of the specific Dll4 signaling in this mechanism. Modulation of IL-6 mediated by ADAM10/Notch signaling required PI3K activity. Thus, our findings suggest that ADAM10/Dll4 signaling is a major signaling pathway in ECs driving inflammatory events involved in inflammation and immune cell recruitment. PMID- 25130544 TI - Distinct mechanisms of cell-kill by triapine and its terminally dimethylated derivative Dp44mT due to a loss or gain of activity of their copper(II) complexes. AB - Triapine, currently being evaluated as an antitumor agent in phase II clinical trials, and its terminally dimethylated derivative Dp44mT share the alpha-pyridyl thiosemicarbazone backbone that functions as ligands for transition metal ions. Yet, Dp44mT is approximately 100-fold more potent than triapine in cytotoxicity assays. The aims of this study were to elucidate the mechanisms underlying their potency disparity and to determine their kinetics of cell-kill in culture to aid in the formulation of their clinical dosing schedules. The addition of Cu(2+) inactivated triapine in a 1:1 stoichiometric fashion, while it potentiated the cytotoxicity of Dp44mT. Clonogenic assays after finite-time drug-exposure revealed that triapine produced cell-kill in two phases, one completed within 20 min that caused limited cell-kill, and the other occurring after 16 h of exposure that produced extensive cell-kill. The ribonucleotide reductase inhibitor triapine at 0.4 MUM caused immediate complete arrest of DNA synthesis, whereas Dp44mT at this concentration did not appreciably inhibit DNA synthesis. The inhibition of DNA synthesis by triapine was reversible upon its removal from the medium. Cell death after 16 h exposure to triapine paralleled the appearance of phospho-(gamma)H2AX, a marker of DNA double-strand breaks induced by collapse of DNA replication forks after prolonged replication arrest. In contrast to triapine, Dp44mT produced robust cell-kill within 1h in a concentration-dependent manner. The short-term action of both agents was prevented by thiols, indicative of the involvement of reactive oxygen species. The time dependency in the production of cell-kill by triapine should be considered in treatment regimens. PMID- 25130546 TI - Identification of one-electron reductases that activate both the hypoxia prodrug SN30000 and diagnostic probe EF5. AB - SN30000 is a second-generation benzotriazine-N-oxide hypoxia-activated prodrug scheduled for clinical trial. Previously we showed that covalent binding of the hypoxia probe EF5 predicts metabolic activation of SN30000 in a panel of cancer cell lines under anoxia, suggesting that they are activated by the same reductases. However the identity of these reductases is unknown. Here, we test whether forced expression of nine oxidoreductases with known or suspected roles in bioreductive prodrug metabolism (AKR1C3, CYB5R3, FDXR, MTRR, NDOR1, NOS2A, NQO1, NQO2 and POR) enhances oxic or anoxic reduction of SN30000 and EF5 by HCT116 cells. Covalent binding of (14)C-EF5 and reduction of SN30000 to its 1 oxide and nor-oxide metabolites was highly selective for anoxia in all lines, with significantly elevated anoxic metabolism of both compounds in lines over expressing POR, MTRR, NOS2A or NDOR1. There was a strong correlation between EF5 binding and SN30000 metabolism under anoxia across the cell lines (R(2)=0.84, p=0.0001). Antiproliferative potency of SN30000 under anoxia was increased most strongly by overexpression of MTRR and POR. Transcript abundance in human tumours, evaluated using public domain mRNA expression data, was highest for MTRR, followed by POR, NOS2A and NDOR1, with little variation between tumour types. Immunostaining of tissue microarrays demonstrated variable MTRR protein expression across 517 human cancers with most displaying low expression. In conclusion, we have identified four diflavin reductases (POR, MTRR, NOS2A and NDOR1) capable of reducing both SN30000 and EF5, further supporting use of 2 nitroimidazole probes to predict the ability of hypoxic cells to activate SN30000. PMID- 25130547 TI - Zinc: an underappreciated modulatory factor of brain function. AB - The divalent cation, zinc is the second most abundant metal in the human body and is indispensable for life. Zinc concentrations must however, be tightly regulated as deficiencies are associated with multiple pathological conditions while an excess can be toxic. Zinc plays an important role as a cofactor in protein folding and function, e.g. catalytic interactions, DNA recognition by zinc finger proteins and modulation ion channel activity. There are 24 mammalian proteins specific for zinc transport that are subdivided in two groups with opposing functions: ZnT proteins reduce cytosolic zinc concentration while ZIP proteins increase it. The mammalian brain contains a significant amount of zinc, with 5 15% concentrated in synaptic vesicles of glutamatergic neurons alone. Accumulated in these vesicles by the ZnT3 transporter, zinc is released into the synaptic cleft at concentrations from nanomolar at rest to high micromolar during active neurotransmission. Low concentrations of zinc modulate the activity of a multitude of voltage- or ligand-gated ion channels, indicating that this divalent cation must be taken into account in the analysis of the pathophysiology of CNS disorders including epilepsy, schizophrenia and Alzheimer's disease. In the context of the latest findings, we review the role of zinc in the central nervous system and discuss the relevance of the most recent association between the zinc transporter, ZIP8 and schizophrenia. An enhanced understanding of zinc transporters in the context of ion channel modulation may offer new avenues in identifying novel therapeutic entities that target neurological disorders. PMID- 25130548 TI - Should we encourage exercise and sports in children and adolescents with cancer? PMID- 25130550 TI - Asymmetric synthesis of agrochemically attractive trifluoromethylated dihydroazoles and related compounds under organocatalysis. AB - The unique, partially saturated, fluorinated five-membered heterocyclic compounds, trifluoromethylated dihydroazoles, and their derivatives, have emerged as a new class of heterocycles with remarkable biological activities in the 21st century. Despite their small molecular structures, a single sterically demanding tetrasubstituted trifluoromethylated stereogenic carbon center has prevented chemists from achieving the asymmetric synthesis of these compounds. In this account, we describe our recent progress in the catalytic asymmetric synthesis of a series of trifluoromethylated heterocycles, such as isoxazolines and pyrrolines having a stereogenic carbon center, based on organocatalysis. Our protocols have advantages in terms of employing inexpensive reagents and organocatalysts and they would be useful for industrial production. PMID- 25130549 TI - Measuring sleep need. PMID- 25130551 TI - The influence of life-history strategy on genetic differentiation and lineage divergence in darters (Percidae: Etheostomatinae). AB - Recent studies determined that darters with specialized breeding strategies can exhibit deep lineage divergence over fine geographic scales without apparent physical barriers to gene flow. However, the extent to which intrinsic characteristics interact with extrinsic factors to influence population divergence and lineage diversification in darters is not well understood. This study employed comparative phylogeographic and population genetic methods to investigate the influence of life history on gene flow, dispersal ability, and lineage divergence in two sympatric sister darters with differing breeding strategies. Our results revealed highly disparate phylogeographic histories, patterns of genetic structure, and dispersal abilities between the two species suggesting that life history may contribute to lineage diversification in darters, especially by limiting dispersal among large river courses. Both species also showed striking differences in demographic history, indicating that extrinsic factors differentially affected each species during the Pleistocene. Collectively, our results indicate that intrinsic and extrinsic factors have influenced levels of gene flow among populations within both species examined. However, we suggest that life-history strategy may play a more important role in lineage diversification in darters than previously appreciated, a finding that has potentially important implications for understanding diversification of the rich North American freshwater fish fauna. PMID- 25130552 TI - Reply: heart donation and the Grinch effect. PMID- 25130553 TI - Left ventricular myocardial response to exercise in children after heart transplant. AB - BACKGROUND: Data on myocardial response to exercise after pediatric heart transplant (HTx) are limited. In this study we used semi-supine bicycle ergometry (SSCE) stress echocardiography to evaluate left ventricular (LV) systolic and diastolic reserve in pediatric HTx recipients. METHODS: Forty-three HTx patients and 23 controls underwent stepwise SSCE stress echocardiography. Color tissue Doppler imaging (TDI) peak systolic (s') and early diastolic (e') velocities in the LV lateral wall and basal septum, and LV peak global longitudinal and circumferential strain were measured at rest and during different stages of exercise. LV myocardial acceleration during isovolumic contraction (IVA) was measured at incremental heart rates (HRs) to determine the force-frequency relationship (FFR). RESULTS: At rest, compared with controls, HTx patients showed lower TDI velocities in the basal septum (s': 4.7 +/- 1.1 vs 5.8 +/- 0.8 cm/s, p = 0.002; e': 8.5 +/- 2.1 vs 11.3 +/- 1.7 cm/s, p < 0.001), whereas in the LV lateral wall only e' was lower (11.2 +/- 2.6 vs 13.8 +/- 2.3 cm/s, p < 0.001). LV IVA was not different between the groups (p = 0.10). LV peak global longitudinal strain was lower in HTx patients (18 +/- 1.9% vs 20 +/- 2.2%, p = 0.001), but peak circumferential strain was not different (p = 0.50). At peak, HR was lower in the HTx group (141 +/- 12 vs 165 +/- 15, p < 0.001), and all systolic and diastolic parameters, except circumferential strain, were lower in HTx recipients. When assessing the increase in TDI and strain values in relation to HR, the slopes were not significantly different between patients and controls. CONCLUSIONS: Despite resting differences in myocardial functional parameters, pediatric HTx recipients have preserved LV diastolic and systolic myocardial reserve in response to exercise. PMID- 25130554 TI - De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation. AB - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of late graft failure after lung transplantation. The objective was to determine whether de novo donor human leukocyte antigen (HLA)-specific antibodies (DSA) are associated with the development of BOS or patient survival. Data were analyzed from 188 lung transplant recipients with a follow-up period up to 8 years. METHODS: HLA antibody monitoring was performed at 3-month intervals post transplant at routine outpatient clinic attendances and during the investigation of any acute deterioration. HLA antibody data were available for 148 patients; 66 (45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA and 28 (19%) non-donor-specific HLA antibodies. RESULTS: De novo DSA was associated with development of BOS Stage 1 (BOS1; hazard ratio [HR] = 2.302, p = 0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo persistent DSA correlated strongly with shorter time to onset of BOS3 (HR = 6.506, p = 0.0001). There was a significant reduction in patient survival associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival. CONCLUSIONS: De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies. PMID- 25130555 TI - Effect of initial surgical palliation on allosensitization and post-transplant outcomes in infants with hypoplastic left heart syndrome. PMID- 25130556 TI - Sulforaphane-induced autophagy flux prevents prion protein-mediated neurotoxicity through AMPK pathway. AB - Prion diseases are neurodegenerative and infectious disorders that involve accumulation of misfolded scrapie prion protein, and which are characterized by spongiform degeneration. Autophagy, a major homeostatic process responsible for the degradation of cytoplasmic components, has garnered attention as the potential target for neurodegenerative diseases such as prion disease. We focused on protective effects of sulforaphane found in cruciferous vegetables on prion mediated neurotoxicity and the mechanism of sulforaphane related to autophagy. In human neuroblastoma cells, sulforaphane protected prion protein (PrP) (106-126) mediated neurotoxicity and increased autophagy flux marker microtubule-associated protein 1 light chain 3-II protein levels, following a decrease of p62 protein level. Pharmacological and genetical inhibition of autophagy by 3MA, wortmannin and knockdown of autophagy-related 5 (ATG5) led to block the effect of sulforaphane against PrP (106-126)-induced neurotoxicity. Furthermore we demonstrated that both sulforaphane-induced autophagy and protective effect of sulforaphane against PrP (106-126)-induced neurotoxicity are dependent on the AMP activated protein kinase (AMPK) signaling. The present results indicated that sulforaphane of cruciferous vegetables enhanced autophagy flux led to the protection effects against prion-mediated neurotoxicity, which was regulated by AMPK signaling pathways in human neuron cells. Our data also suggest that sulforaphane has a potential value as a therapeutic tool in neurodegenerative disease including prion diseases. PMID- 25130557 TI - Contribution of Ih to the relative facilitation of synaptic responses induced by carbachol in the entorhinal cortex during repetitive stimulation of the parasubiculum. AB - Neurons in the superficial layers of the entorhinal cortex provide the hippocampus with the majority of its cortical sensory input, and also receive the major output projection from the parasubiculum. This puts the parasubiculum in a position to modulate the activity of entorhinal neurons that project to the hippocampus. These brain areas receive cholinergic projections that are active during periods of theta- and gamma-frequency electroencephalographic (EEG) activity. The purpose of this study was to investigate how cholinergic receptor activation affects the strength of repetitive synaptic responses at these frequencies in the parasubiculo-entorhinal pathway and the cellular mechanisms involved. Whole-cell patch-clamp recordings of rat layer II medial entorhinal neurons were conducted using an acute slice preparation, and responses to 5-pulse trains of stimulation at theta- and gamma-frequency delivered to the parasubiculum were recorded. The cholinergic agonist carbachol (CCh) suppressed the amplitude of single synaptic responses, but also produced a relative facilitation of synaptic responses evoked during stimulation trains. The N-methyl d-aspartate (NMDA) glutamate receptor blocker APV did not significantly reduce the relative facilitation effect. However, the hyperpolarization-activated cationic current (Ih) channel blocker ZD7288 mimicked the relative facilitation induced by CCh, suggesting that CCh-induced inhibition of Ih could produce the effect by increasing dendritic input resistance (Rin). Inward-rectifying and leak K(+) currents are known to interact with Ih to affect synaptic excitability. Application of the K(+) channel antagonist Ba(2+) depolarized neurons and enhanced temporal summation, but did not block further facilitation of train evoked responses by ZD7288. The Ih-dependent facilitation of synaptic responses can therefore occur during reductions in inward-rectifying potassium current (IKir) associated with dendritic depolarization. Thus, in addition to cholinergic reductions in transmitter release that are known to facilitate train-evoked responses, these findings emphasize the role of inhibition of Ih in the integration of synaptic inputs within the entorhinal cortex during cholinergically-induced oscillatory states, likely due to enhanced summation of excitatory postsynaptic potentials (EPSPs) induced by increases in dendritic Rin. PMID- 25130558 TI - Diphenyl-diselenide suppresses amyloid-beta peptide in Caenorhabditis elegans model of Alzheimer's disease. AB - Alzheimer's disease (AD) is the most common and devastating neurodegenerative disease. The etiology of AD has yet to be fully understood, and common treatments remain largely non-efficacious. The amyloid hypothesis posits that extracellular amyloid-beta (Abeta) deposits are the fundamental etiological factor of the disease. The present study tested the organoselenium compound diphenyl-diselenide (PhSe)2, which is characterized by its antioxidant and antiinflammatory properties and has shown efficacy in several neurodegenerative disease models. We employed a transgenic Caenorhabditis elegans AD model to analyze the effects of (PhSe)2 treatment on Abeta peptide-induced toxicity. Chronic exposure to (PhSe)2 attenuated oxidative stress induced by Abeta1-42, with concomitant recovery of associative learning memory in C. elegans. Additionally, (PhSe)2 decreased Abeta1 42 transgene expression, suppressed Abeta1-42 peptide, and downregulated hsp-16.2 by reducing the need for this chaperone under Abeta1-42-induced toxicity. These observations suggest that (PhSe)2 plays an important role in protecting against oxidative stress-induced toxicity, thus representing a promising pharmaceutical modality that attenuates Abeta1-42 expression. PMID- 25130560 TI - 5-HT3A receptors are required in long-term depression and AMPA receptor internalization. AB - 5-Hydroxytrytamine (serotonin) type 3A receptors (5-HT3ARs), as the only ligand gated ion channels in the serotonin receptor family, are known to regulate neuronal excitation and release of GABA in hippocampal interneurons. However, their physiological role in glutamatergic synaptic plasticity remains unclear. Here, we show that deletion of the 5-HT3AR gene in transgenic mice abolished N methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD) induced by low-frequency stimulation (LFS) in hippocampal CA1 synapses in slices, whereas the metabotropic glutamate receptor (mGluR)-dependent LTD did not change in the 5-HT3AR knockout mice. In addition, 5-HT3ARs disruption inhibited alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) internalization, without altering basal surface levels of AMPARs. However, the deletion of 5-HT3ARs did not lead to loss of synapses and structural alteration of dendritic spines. Furthermore, the concentrations of 5-HT and 5 hydroxyindoleacetic acid (5-HIAA) in the hippocampus were not affected by the deletion of 5-HT3ARs. These observations revealed an important role of 5-HT3ARs in NMDAR-dependent long-term depression, which is critical for learning behaviors. PMID- 25130559 TI - Downstream effects of striatal-enriched protein tyrosine phosphatase reduction on RNA expression in vivo and in vitro. AB - Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific tyrosine phosphatase that has been shown to de-phosphorylate several key neuronal signaling proteins, including kinases (extracellular signal-regulated kinase (ERK1/2), FYN, PYK2) and glutamate receptor subunits (N-methyl-d-aspartate receptor subtype 2B (NR2B), glutamate receptor 2 (GLUR2)). Step knock-out mice have increased phosphorylation of these substrates in the brain, with potential functional consequences in synaptic plasticity and cognitive tasks. It is therefore of interest to identify the molecular pathways and downstream transcriptional targets that are impacted by Step knockdown. In the present study, striatal RNA samples from Step wild-type, knock-out and heterozygous mice were hybridized to Affymetrix microarray chips and evaluated for transcriptional changes between genotypes. Pathway analysis highlighted Erk signaling and multiple pathways related to neurotrophin signaling, neuronal development and synaptic transmission. Potential genes of interest identified by microarray were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) in the cortex and hippocampus, which shared several transcriptional alterations with the striatum. In order to evaluate Step knockdown in an in vitro system, a panel of genes were evaluated using qRT-PCR in rat cortical neurons that were transduced with lentivirus expressing short hairpin RNA against Step or a non-targeting control. Our data suggest that Step has a role in the expression of immediate early genes relevant to synaptic plasticity, in both in vitro and in vivo systems. PMID- 25130562 TI - Maternal administration of flutamide during late gestation affects the brain and reproductive organs development in the rat male offspring. AB - We have previously demonstrated that male rats exposed to stress during the last week of gestation present age-specific impairments of brain development. Since the organization of the fetal developing brain is subject to androgen exposure and prenatal stress was reported to disrupt perinatal testosterone surges, the aim of this research was to explore whether abnormal androgen concentrations during late gestation affects the morphology of the prefrontal cortex (PFC), hippocampus (HPC) and ventral tegmental area (VTA), three major areas that were shown to be affected by prenatal stress in our previous studies. We administered 10-mg/kg/day of the androgen receptor antagonist flutamide (4'nitro-3' trifluoromethylsobutyranilide) or vehicle injections to pregnant rats from days 15-21 of gestation. The antiandrogenic effects of flutamide were confirmed by the analysis of androgen-dependent developmental markers: flutamide-exposed rats showed reduced anogenital distance, delay in the completion of testis descent, hypospadias, cryptorchidism and atrophied seminal vesicles. Brain morphological studies revealed that prenatal flutamide decreased the number of MAP2 (a microtubule-associated protein type 2, present almost exclusively in dendrites) immunoreactive neuronal processes in all evaluated brain areas, both in prepubertal and adult offspring, suggesting that prenatal androgen disruption induces long-term reductions of the dendritic arborization of several brain structures, affecting the normal connectivity between areas. Moreover, the number of tyrosine hydroxylase (TH)-immunopositive neurons in the VTA of prepubertal offspring was reduced in flutamide rats but reach normal values at adulthood. Our results demonstrate that the effects of prenatal flutamide on the offspring brain morphology resemble several prenatal stress effects suggesting that the mechanism of action of prenatal stress might be related to the impairment of the organizational role of androgens on brain development. PMID- 25130561 TI - Age-related increases in right frontal activation during task switching are mediated by reaction time and white matter microstructure. AB - Age-related increases in right frontal cortex activation are a common finding in the neuroimaging literature. However, neurocognitive factors contributing to right frontal over-recruitment remain poorly understood. Here we investigated the influence of age-related reaction time (RT) slowing and white matter (WM) microstructure reductions as potential explanatory factors for age-related increases in right frontal activation during task switching. Groups of younger (N=32) and older (N=33) participants completed a task switching paradigm while functional magnetic resonance imaging (fMRI) was performed, and rested while diffusion tensor imaging (DTI) was performed. Two right frontal regions of interest (ROIs), the dorsolateral prefrontal cortex (DLPFC) and insula, were selected for further analyses from a common network of regions recruited by both age groups during task switching. Results demonstrated age-related activation increases in both ROIs. In addition, the older adult group showed longer RT and decreased fractional anisotropy in regions of the corpus callosum with direct connections to the fMRI ROIs. Subsequent mediation analyses indicated that age related increases in right insula activation were mediated by RT slowing and age related increases in right DLPFC activation were mediated by WM microstructure. Our results suggest that age-related RT slowing and WM microstructure declines contribute to age-related increases in right frontal activation during cognitive task performance. PMID- 25130564 TI - Sea surface temperature contributes to marine crocodylomorph evolution. AB - During the Mesozoic and Cenozoic, four distinct crocodylomorph lineages colonized the marine environment. They were conspicuously absent from high latitudes, which in the Mesozoic were occupied by warm-blooded ichthyosaurs and plesiosaurs. Despite a relatively well-constrained stratigraphic distribution, the varying diversities of marine crocodylomorphs are poorly understood, because their extinctions neither coincided with any major biological crises nor with the advent of potential competitors. Here we test the potential link between their evolutionary history in terms of taxic diversity and two abiotic factors, sea level variations and sea surface temperatures (SST). Excluding Metriorhynchoidea, which may have had a peculiar ecology, significant correlations obtained between generic diversity and estimated Tethyan SST suggest that water temperature was a driver of marine crocodylomorph diversity. Being most probably ectothermic reptiles, these lineages colonized the marine realm and diversified during warm periods, then declined or became extinct during cold intervals. PMID- 25130565 TI - Catalytic constructive deoxygenation of lignin-derived phenols: new C-C bond formation processes from imidazole-sulfonates and ether cleavage reactions. AB - As part of a programme aimed at exploiting lignin as a chemical feedstock for less oxygenated fine chemicals, several catalytic C-C bond forming reactions utilising guaiacol imidazole sulfonate are demonstrated. These include the cross coupling of a Grignard, a non-toxic cyanide source, a benzoxazole, and nitromethane. A modified Meyers reaction is used to accomplish a second constructive deoxygenation on a benzoxazole functionalised anisole. PMID- 25130563 TI - The network property of the thalamus in the default mode network is correlated with trait mindfulness. AB - Mindfulness is typically defined as nonjudgmental awareness of experiences in the present moment, which is beneficial for mental and physical well-being. Previous studies have identified multiple regions in the default mode network (DMN) that are involved in mindfulness, but little is known about how these regions work collaboratively as a network. Here, we used resting-state functional magnetic resonance imaging to investigate the role of the DMN in trait mindfulness by correlating spontaneous functional connectivity among DMN nodes with self reported trait mindfulness in a large population of young human adults. Among all pairs of the DMN nodes, we found that individuals with weaker functional connectivity between the thalamus and posterior cingulate cortex (PCC) were more mindful of the present. Post-hoc analyses of these two nodes further revealed that graph-based nodal properties of the thalamus, not the PCC, were negatively correlated with trait mindfulness, suggesting that a low involvement of the thalamus in the DMN is relevant for high trait mindfulness. Our findings not only suggest the thalamus as a switch between mind-wandering and mindfulness, but also invite future studies on mechanisms of how mindfulness produces beneficial effects by modulating the thalamus. PMID- 25130566 TI - Radiobiological modeling and the study of hypofractionated radiotherapy for prostate cancer. PMID- 25130567 TI - Does reduced feeding prior to release improve the marine migration of hatchery brown trout Salmo trutta smolts? AB - The aim of this study was to test the hypothesis that hatchery brown trout Salmo trutta smolts, with 50% reduced or no feeding over the last 5 months before release, were more likely to migrate to the sea than individuals with standard feeding ratios. The juvenile fish were divided into three groups 176 days before release: (A) with no feeding, (B) with 50% and (C) with 100% feeding. To study their seaward migration, 40 fish from each feeding group were tagged with acoustic transmitters and tracked by automatic listening stations in the River Nidelva, Trondheim, Norway, its estuary and in the nearest marine environment. At the time of release, mean condition factor was significantly lower in group A and the fish from groups A and B had higher levels of Na+, K+-ATPase. Significantly more fish from group A migrated to the sea, but the rate of downstream progression from release to the estuary did not differ between the three groups. In conclusion, the S. trutta smolts with no access to food in the last 176 day before release were more likely to migrate to the sea. Fish from all three feeding groups, however, appeared to smoltify and had the same rate of downstream progression to the estuary. This indicates that differences in migratory behaviour between individuals from the three feeding groups begin from the time when the fish reach saline waters. It is suggested that feeding in hatcheries has to be greatly reduced (by 50% or more) over several months to have a pronounced effect on the migratory behaviour in S. trutta. PMID- 25130568 TI - First-episode affective psychosis and lipid monitoring: survival analysis of the first abnormal lipid test. AB - AIM: This study aimed to assess the probability of developing a lipid test abnormality over time, among first-time users of antipsychotic medications with affective psychosis. METHODS: Survival analysis was used to analyse data from an early intervention in psychosis programme for the first 53 consecutive and eligible cases of patients between the ages of 14 and 40 years who had a diagnosis of affective psychosis. Data on initiation of antipsychotic medications and lipid laboratory test results were abstracted from chart reviews. RESULTS: Within the first 18 months of receiving antipsychotic medications, the probability of surviving without an abnormal lipid test was only 25% (confidence interval 95%: 13.1%, 40.4%). The median time to the development of an abnormal test was 8 months for males and 12 months for females (P < 0.001). CONCLUSIONS: Additional studies are needed to document the incidence over time of abnormal lipid tests to inform clinicians about the optimal frequency of monitoring. PMID- 25130569 TI - Overall ED efficiency is associated with decreased time to percutaneous coronary intervention for ST-segment elevation myocardial infarction. AB - BACKGROUND: Performance of percutaneous coronary intervention (PCI) within 90 minutes of hospital arrival for ST-segment elevation myocardial infarction patients is a commonly cited clinical quality measure. The Centers for Medicare and Medicaid Services use this measure to adjust hospital reimbursement via the Value-Based Purchasing Program. This study investigated the relationship between hospital performance on this quality measure and emergency department (ED) operational efficiency. METHODS: Hospital-level data from Centers for Medicare and Medicaid Services on PCI quality measure performance was linked to information on operational performance from 272 US EDs obtained from the Emergency Department Benchmarking Alliance annual operations survey. Standard metrics of ED size, acuity, and efficiency were compared across hospitals grouped by performance on the door-to-balloon time quality measure. RESULTS: Mean hospital performance on the 90-minute arrival to PCI measure was 94.0% (range, 42 100). Among hospitals failing to achieve the door-to-balloon time performance standard, median ED length of stay was 209 minutes, compared with 173 minutes among those hospitals meeting the benchmark standard (P < .001). Similarly, median time from ED patient arrival to physician evaluation was 39 minutes for hospitals below the performance standard and 23 minutes for hospitals at the benchmark standard (P < .001). Markers of ED size and acuity, including annual patient volume, admission rate, and the percentage of patients arriving via ambulance did not vary with door-to-balloon time. CONCLUSION: Better performance on measures associated with ED efficiency is associated with more timely PCI performance. PMID- 25130570 TI - Rhodium-coordinated poly(arylene-ethynylene)-alt-poly(arylene-vinylene) copolymer acting as photocatalyst for visible-light-powered NAD+/NADH reduction. AB - A 2,2'-bipyridyl-containing poly(arylene-ethynylene)-alt-poly(arylene-vinylene) polymer, acting as a light-harvesting ligand system, was synthesized and coupled to an organometallic rhodium complex designed for photocatalytic NAD(+)/NADH reduction. The material, which absorbs over a wide spectral range, was characterized by using various analytical techniques, confirming its chemical structure and properties. The dielectric function of the material was determined from spectroscopic ellipsometry measurements. Photocatalytic reduction of nucleotide redox cofactors under visible light irradiation (390-650 nm) was performed and is discussed in detail. The new metal-containing polymer can be used to cover large surface areas (e.g. glass beads) and, due to this immobilization step, can be easily separated from the reaction solution after photolysis. Because of its high stability, the polymer-based catalyst system can be repeatedly used under different reaction conditions for (photo)chemical reduction of NAD(+). With this concept, enzymatic, photo-biocatalytic systems for solar energy conversion can be facilitated, and the precious metal catalyst can be recycled. PMID- 25130571 TI - Randomized trial of human milk cream as a supplement to standard fortification of an exclusive human milk-based diet in infants 750-1250 g birth weight. AB - OBJECTIVE: To evaluate whether premature infants who received an exclusive human milk (HM)-based diet and a HM-derived cream supplement (cream) would have weight gain (g/kg/d) at least as good as infants receiving a standard feeding regimen (control). STUDY DESIGN: In a prospective noninferiority, randomized, unmasked study, infants with a birth weight 750-1250 g were randomly assigned to the control or cream group. The control group received mother's own milk or donor HM with donor HM-derived fortifier. The cream group received a HM-derived cream supplement if the energy density of the HM tested <20 kcal/oz using a near infrared HM analyzer. Infants were continued on the protocol until 36 weeks postmenstrual age. Primary outcomes included growth velocities and amount of donor HM-derived fortifier used. The hypothesis of noninferiority was established if the lower bound of the one-sided 95% CI for the difference in weight velocities exceeded -3 g/kg/day. RESULTS: There were no differences between groups in baseline demographics for the 78 infants studied except racial distribution (P = .02). The cream group (n = 39) had superior weight (14.0 +/- 2.5 vs 12.4 +/- 3.0 g/kg/d, P = .03) and length (1.03 +/- 0.33 vs 0.83 +/- 0.41 cm/wk, P = .02) velocity compared with the control group (n = 39). There were no significant differences in amount of fortifier used between study groups. The 1 sided 95% lower bound of the CI for the difference in mean velocity (cream control) was 0.38 g/kg/d. CONCLUSIONS: Premature infants who received HM-derived cream to fortified HM had improved weight and length velocity compared with the control group. HM-derived cream should be considered an adjunctive supplement to an exclusive HM-based diet to improve growth rates in premature infants. PMID- 25130573 TI - Cultural adaptation of preschool PATHS (Promoting Alternative Thinking Strategies) curriculum for Pakistani children. AB - Cultural adaptation of evidence-based programmes has gained importance primarily owing to its perceived impact on the established effectiveness of a programme. To date, many researchers have proposed different frameworks for systematic adaptation process. This article presents the cultural adaptation of preschool Promoting Alternative Thinking Strategies (PATHS) curriculum for Pakistani children using the heuristic framework of adaptation (Barrera & Castro, 2006). The study was completed in four steps: information gathering, preliminary adaptation design, preliminary adaptation test and adaptation refinement. Feedbacks on programme content suggested universality of the core programme components. Suggested changes were mostly surface structure: language, presentation of materials, conceptual equivalence of concepts, training needs of implementation staff and frequency of programme delivery. In-depth analysis was done to acquire cultural equivalence. Pilot testing of the outcome measures showed strong internal consistency. The results were further discussed with reference to similar work undertaken in other cultures. PMID- 25130572 TI - An automated system using spatial oversampling for optical mapping in murine atria. Development and validation with monophasic and transmembrane action potentials. AB - We developed and validated a new optical mapping system for quantification of electrical activation and repolarisation in murine atria. The system makes use of a novel 2nd generation complementary metal-oxide-semiconductor (CMOS) camera with deliberate oversampling to allow both assessment of electrical activation with high spatial and temporal resolution (128 * 2048 pixels) and reliable assessment of atrial murine repolarisation using post-processing of signals. Optical recordings were taken from isolated, superfused and electrically stimulated murine left atria. The system reliably describes activation sequences, identifies areas of functional block, and allows quantification of conduction velocities and vectors. Furthermore, the system records murine atrial action potentials with comparable duration to both monophasic and transmembrane action potentials in murine atria. PMID- 25130574 TI - JSAP1 and JLP are required for ARF6 localization to the midbody in cytokinesis. AB - The ADP-ribosylation factor 6 (ARF6) GTPase is important in cytokinesis and localizes to the midbody. However, the mechanism and regulation of ARF6's recruitment to the midbody are largely unknown. Here, we investigated the functions of two binding partners of active ARF6, c-Jun NH2 -terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) and JNK associated leucine zipper protein (JLP), by gene knockout and rescue experiments in mouse embryonic fibroblasts. Depleting both JSAP1 and JLP impaired ARF6's localization to the midbody and delayed cytokinesis. These defects were almost completely rescued by wild-type JSAP1 or JLP, but not by JSAP1 or JLP mutants that were unable to interact with active ARF6 or with the kinesin heavy chain (KHC) of kinesin-1. In transfected cells, a constitutively active form of ARF6 associated with KHC only when co-expressed with wild-type JSAP1 or JLP and not with a JSAP1 or JLP mutant. These findings suggest that JSAP1 and JLP, which might be paralogous to each other, are critical and functionally redundant in cytokinesis and control ARF6 localization to the midbody by forming a tripartite complex of JSAP1/JLP, active ARF6, and kinesin-1. PMID- 25130576 TI - A possible means of countering the underdiagnosis of Klinefelter Syndrome. PMID- 25130578 TI - New insights into SET protein during mouse spermatogenesis. PMID- 25130577 TI - Testicular parenchymal abnormalities in Klinefelter syndrome: a question of cancer? Examination of 40 consecutive patients. AB - Klinefelter syndrome (KS) is a hypergonadotropic hypogonadism characterized by a 47, XXY karyotype. The risk of testicular cancer in KS is of interest in relation to theories about testicular cancer etiology generally; nevertheless it seems to be low. We evaluated the need for imaging and serum tumor markers for testicular cancer screening in KS. Participants were 40 consecutive KS patients, enrolled from December 2009 to January 2013. Lactate dehydrogenase (LDH), alpha fetoprotein (AFP), and beta-human chorionic gonadotrophin subunit (beta-HCG) serum levels assays and testicular ultrasound (US) with color Doppler, were carried out at study entry, after 6 months and every year for 3 years. Abdominal magnetic resonance (MR) was performed in KS when testicular US showed micro calcifications, testicular nodules and cysts. Nearly 62% of the KS had regular testicular echotexture, 37.5% showed an irregular echotexture and 17.5% had micro calcifications and cysts. Eighty seven percent of KS had a regular vascular pattern, 12.5% varicocele, 12.5% nodules <1 cm, but none had nodules >1 cm. MR ruled out the diagnosis of cancer in all KS with testicular micro calcifications, nodules and cysts. No significant variations in LDH, AFP, and beta-HCG levels and in US pattern have been detected during follow-up. We compared serum tumor markers and US pattern between KS with and without cryptorchidism and no statistical differences were found. We did not find testicular cancer in KS, and testicular US, tumor markers and MR were, in selected cases, useful tools for correctly discriminating benign from malignant lesions. PMID- 25130580 TI - Bacteria and the prostate: infertility versus symptoms. PMID- 25130581 TI - Glucocorticoid metabolism in testicular tissue: a key to fertility? PMID- 25130582 TI - Complex and time-consuming laboratory modifications are not always necessary to improve outcome. PMID- 25130583 TI - The impact of male overweight on semen quality and outcome of assisted reproduction. PMID- 25130584 TI - Prevention of erectile dysfunction after radiotherapy for prostate cancer. AB - With increasing scrutiny of prostate cancer (PCa) diagnosis and treatment, much attention has been given to the morbidity caused by radical prostatectomy (RP) and/or radiotherapy (RT). One of the most common side-effects of either treatment is erectile dysfunction (ED). Approximately, 40% of patients will experience ED after RT for PCa. The post-RT ED causes significant patient dissatisfaction with cancer treatment as well as decrease in patient and partner psychosocial function. To address this issue in patients undergoing RT, Pisansky et al. conducted a prospective, randomized, double-blinded, placebo-controlled trial to assess the efficacy of a phosphodiesterase enzyme-5 inhibitor (PDE5i), tadalafil, as a preventive measure for patients undergoing RT for PCa and found no difference in erectile function between the control and treatment groups. PMID- 25130585 TI - Circumcision standards: can we improve further? PMID- 25130586 TI - Male patients with terminal renal failure exhibit low serum levels of antimullerian hormone. AB - Male reproductive function is impaired during end-stage renal disease (ESRD). Disturbance of the hypothalamic-pituitary-gonadal axis, and therefore the regulation of sex hormones, is one of the major causes. Our focus was to include antimullerian hormone (AMH) and inhibin B concentrations. Twenty male patients on hemodialysis, median age 40 (26-48) years, were analyzed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, sex hormone-binding globulin (SHBG), testosterone, estradiol, AMH and inhibin B levels. We used 144 proven fertile men, median age 32 (19-44) years as a control group and analyzed differences using multiple linear regression. Males with ESRD demonstrated higher mean values for prolactin, 742 versus normal 210 mIE l-1 (95% confidence interval (CI): 60.3, 729), LH, 8.87 versus normal 4.5 IE l-1 (95% CI: 2.75, 6.14), and estradiol 89.7 versus normal 79.0 pmol l-1 (95% CI: -1.31, -0.15). Mean value for AMH was lower, 19.5 versus normal 47.3 pmol l-1 (95% CI: -37.6, -11.6). There were no differences found for FSH, SHBG, inhibin B and testosterone. The most important difference was found for AMH, a marker of Sertoli cell function in the testes, which decreased by close to 60% when compared with controls. Combined with an increase in LH, these findings may indicate a dysfunction of Sertoli cells and an effect on Leydig cells contributing to a potential mechanism of reproductive dysfunction in men with ESRD. PMID- 25130587 TI - Region 2 of 8q24 is associated with the risk of aggressive prostate cancer in Caribbean men of African descent from Guadeloupe (French West Indies). AB - Multiple regions of the genome have been associated with the risk of prostate cancer in Caucasians, particularly including several polymorphisms located at 8q24. Region 2 of 8q24 has been repeatedly found to be associated with the risk of prostate cancer among men of African descent, although one study performed in the Caribbean island of Jamaica did not report this finding. In this study, the single nucleotide polymorphism rs16901979, located in region 2 of 8q24, was genotyped in 498 cases of histologically confirmed prostate cancer and 541 controls from the French Caribbean islands of Guadeloupe, where the population is largely of African descent. The AA genotype and the A allele at rs16901979 were associated with elevated risks of prostate cancer (odds ratios [ORs] = 1.84, 95% confidence interval [95% CI] = 1.26-2.69, P = 0.002 and OR = 1.36, 95% CI = 1.13 1.64, P = 0.001, respectively). Following stratification of the patients by disease aggressiveness, as defined by the Gleason score, the pooled genotypes AC + AA were associated with a higher risk of a Gleason score >=7 at diagnosis (OR = 1.79, 95% CI = 1.17-2.73, P = 0.007). In summary, the A allele at rs16901979 was associated with the risk of prostate cancer in the Caribbean population of Guadeloupe, confirming its involvement in populations of African descent. Moreover, our study provides the first evidence of an association between this variant and the risk of aggressive prostate cancer. PMID- 25130589 TI - Stress modulation of cellular metabolic sensors: interaction of stress from temperature and rainfall on the intertidal limpet Cellana toreuma. AB - In the natural environment, organisms are exposed to large variations in physical conditions. Quantifying such physiological responses is, however, often performed in laboratory acclimation studies, in which usually only a single factor is varied. In contrast, field acclimatization may expose organisms to concurrent changes in several environmental variables. The interactions of these factors may have strong effects on organismal function. In particular, rare events that occur stochastically and have relatively short duration may have strong effects. The present experiments studied levels of expression of several genes associated with cellular stress and metabolic regulation in a field population of limpet Cellana toreuma that encountered a wide range of temperatures plus periodic rain events. Physiological responses to these variable conditions were quantified by measuring levels of mRNA of genes encoding heat-shock proteins (Hsps) and metabolic sensors (AMPKs and Sirtuin 1). Our results reveal high ratios of individuals in upregulation group of stress-related gene expression at high temperature and rainy days, indicating the occurrence of stress from both prevailing high summer temperatures and occasional rainfall during periods of emersion. At high temperature, stress due to exposure to rainfall may be more challenging than heat stress alone. The highly variable physiological performances of limpets in their natural habitats indicate the possible differences in capability for physiological regulation among individuals. Our results emphasize the importance of studies of field acclimatization in unravelling the effects of environmental change on organisms, notably in the context of multiple changes in abiotic factors that are accompanying global change. PMID- 25130588 TI - Nematode resistance to ivermectin (630 and 700MUg/kg) in cattle from the Southeast and South of Brazil. AB - Two high doses of ivermectin (630MUg/kg and 700MUg/kg) that are sold commercially in Brazil were evaluated in dose-and-slaughter trials with 144 naturally nematode infected cattle from eight regions within the states of Minas Gerias, Sao Paulo and Rio Grande do Sul in Brazil. Treatment groups were based on fecal egg counts 1, 2, and 3days before treatment; all animals studied had a minimum egg count of at least 500 eggs per gram of feces (EPG). Post-mortem analyses were conducted on day 14. The highest levels of resistance to ivermectin were found for Haemonchus placei, Cooperia punctata and Oesophagostomum radiatum; all populations of H. placei were resistant to the 630MUg/kg dose, and 67% were resistant to 700MUg/kg; 86% of C. punctata were resistant to the 630MUg/kg dose, and 33% were resistant to 700MUg/kg. A combined analysis revealed that 57% of O. radiatum were resistant to the lower dose of ivermectin. H. placei, C. punctata and O. radiatum, in order, were the nematode populations with the highest indices of resistance, whereas Trichostrongylus axei was the most susceptible to 630 and 700MUg/kg dosages of ivermectin. The results of helminthic resistance to ivermectin for different populations of H. placei and C. punctata described in the present study support previous literature data, in which a small decrease in the average parasitic burden of C. punctata and a consequent increase of H. placei were observed in cattle from the Southeast, South and Center-West regions of Brazil. PMID- 25130591 TI - Dominant components of the Thoroughbred metabolome characterised by (1) H-nuclear magnetic resonance spectroscopy: A metabolite atlas of common biofluids. AB - REASONS FOR PERFORMING STUDY: Metabonomics is emerging as a powerful tool for disease screening and investigating mammalian metabolism. This study aims to create a metabolic framework by producing a preliminary reference guide for the normal equine metabolic milieu. OBJECTIVES: To metabolically profile plasma, urine and faecal water from healthy racehorses using high resolution (1) H nuclear magnetic resonance (NMR) spectroscopy and to provide a list of dominant metabolites present in each biofluid for the benefit of future research in this area. STUDY DESIGN: This study was performed using 7 Thoroughbreds in race training at a single time point. Urine and faecal samples were collected noninvasively and plasma was obtained from samples taken for routine clinical chemistry purposes. METHODS: Biofluids were analysed using (1) H-NMR spectroscopy. Metabolite assignment was achieved via a range of one- and 2 dimensional experiments. RESULTS: A total of 102 metabolites were assigned across the 3 biological matrices. A core metabonome of 14 metabolites was ubiquitous across all biofluids. All biological matrices provided a unique window on different aspects of systematic metabolism. Urine was the most populated metabolite matrix with 65 identified metabolites, 39 of which were unique to this biological compartment. A number of these were related to gut microbial host cometabolism. Faecal samples were the most metabolically variable between animals; acetate was responsible for the majority (28%) of this variation. Short chain fatty acids were the predominant features identified within this biofluid by (1) H-NMR spectroscopy. CONCLUSIONS: Metabonomics provides a platform for investigating complex and dynamic interactions between the host and its consortium of gut microbes and has the potential to uncover markers for health and disease in a variety of biofluids. Inherent variation in faecal extracts along with the relative abundance of microbial-mammalian metabolites in urine and invasive nature of plasma sampling, infers that urine is the most appropriate biofluid for the purposes of metabonomic analysis. PMID- 25130592 TI - Does Synergy Exist in Nursing? A Concept Analysis. AB - AIM: The aim is to analyze the concept of synergy, particularly as the concept applies to teamwork, and determine if the concept has utility in improving the work environment for nurses. Tackling nursing shortages that result from a poor work environment is a priority for many nurse leaders. Producing synergy among teams may be an effective strategy in enhancing the work environment. However, the understanding of synergy and the ability to produce synergy among teams has been seldom highlighted or discussed within nursing literature. Walker and Avant's approach was used to guide this concept analysis of synergy. SOURCES: Literature searches involved databases (PsycInfo, Medline, Cumulative Index for Nursing and Allied Health Literature [CINAHL], and Scopus), Internet search engines (Google), and hand searches. CONCLUSION: The analysis suggests that synergy is an outcome of the successful collaboration of the following three attributes: group cohesion, the pursuit of a common goal, and the achievement of a positive gain, considerably more than what was thought possible by the group. The foundation for this accomplishment requires an underlying feeling of special importance, the acknowledgment of each member's role, and open communication and dialogue among members. Nursing leaders would benefit from a broader understanding of synergy, and the mindful application and utility of synergy as an outcome of effective teamwork among nurses. PMID- 25130590 TI - Histone acetylation in the nucleus accumbens shell modulates ethanol-induced locomotor activity in DBA/2J mice. AB - BACKGROUND: A growing body of literature suggests that epigenetic mechanisms, including histone acetylation, may play key roles in drug abuse and the development of addiction. Experiments in this study were designed to investigate the role of histone acetylation in ethanol (EtOH)-induced locomotor sensitization. METHODS: Immunohistochemical, Western blotting, and site-directed pharmacological techniques were used to explore the roles of histone acetylation at histone H3 (acH3K9) in both the expression of and acquisition of EtOH-induced locomotor sensitization. A commonly used sensitization protocol, in which animals were exposed to repeated injections of a low dose of EtOH while in their home cage, was used to examine this behavioral phenomenon. Additionally, site-directed administration of the histone deacetylase inhibitor (HDACi) Trichostatin A (TSA), in the absence of repeated EtOH injections, was used to examine the role of hyperacetylation in the nucleus accumbens (NAC) shell in EtOH-induced locomotor sensitization. RESULTS: Sensitized mice displayed elevated acH3K9 immunoreactivity (IR) localized to the shell of the NAC. This augmentation in acH3K9 IR was confirmed, in a separate experiment, using Western blot analyses. Next, repeated intra-accumbal infusions of TSA, in the absence of repeated EtOH injections, were sufficient to induce an augmented locomotor response to a later injection of a low dose (2.0 g/kg, intraperitoneally) of EtOH, indicative of cross-sensitization to this locomotor stimulation between TSA and EtOH. Finally, a local infusion of TSA into the shell of the accumbens was also associated with a significant increase in acH3K9 IR within this region. CONCLUSIONS: Together, the present observations suggest that histone acetylation, particularly within the shell of the NAC, is important for the development and expression of EtOH induced locomotor sensitization. PMID- 25130594 TI - Benzodithiophene based pi-conjugated macrocycles: synthesis, morphology and electrochemical characterization. AB - A 7,8-didodecyloxybenzo[1,2-b:4,3-b']dithiophene (BdT-Dod) containing a macrocycle was synthesized from a thiophene capped BdT-Dod comonomer through a Ti(iv) mediated McMurry reaction and characterized by (1)H NMR, (13)C NMR and MALDI-TOF mass spectrometry. Additionally, the morphological characterization was performed by AFM and SEM to investigate the self-aggregation properties. The macrocycle underwent self-assembly in the solid state to form fibers on the Si/SiO2 surface with a length in the MUm range and a thickness of about 400 nm. PMID- 25130593 TI - Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study. AB - OBJECTIVES: To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) >=30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. RESULTS: Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI >=30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score >=7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. CONCLUSION: In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer. PMID- 25130595 TI - The birth of an infant decreases group spacing in a zoo-housed lowland gorilla group (Gorilla gorilla gorilla). AB - Changes in group composition can alter the behavior of social animals such as gorillas. Although gorilla births are presumed to affect group spacing patterns, there is relatively little data about how these events affect gorilla group cohesion. We investigated how members of a western lowland gorilla group (n = 6) at Lincoln Park Zoo (Chicago, IL, USA) spaced themselves prior to and after the birth of an infant, to investigate changes in group cohesion. Gorillas were housed in an indoor-outdoor enclosure in which access to the outdoors was permitted when temperatures exceeded 5 degrees C. We recorded spatial locations of each group member using 30-min group scans on tablet computers with an electronic map interface, as well as noting their access to outdoor areas. Data from the 4 months following the birth was compared to a control period corresponding to early pregnancy. We measured distances between all possible group dyads for each scan and subsequently calculated a mean distance between all group members. An ANOVA revealed that access to the outdoors had no effect on group spacing (F(1,56) = 0.066, P = 0.799). However, the presence of an infant resulted in a significant reduction in inter-individual distance (F(1,56) = 23.988, P = 0.000), decreasing inter-individual spacing by 12.5%. This information helps characterize the behavioral impact of a new birth on captive gorilla social structure and could potentially inform future management of breeding gorilla groups. PMID- 25130596 TI - Social participation and health-related quality of life in people with multiple sclerosis. AB - BACKGROUND: Social participation is an integral part of everyday life in society; however, evidence about its association with health-related quality of life (HRQoL) in people with multiple sclerosis (MS) is lacking. OBJECTIVE: The aim of this study is to explore whether social participation is associated with the Physical Component Summary of HRQoL (PCS) and Mental Component Summary of HRQoL (MCS) in people with MS, controlled for age, gender, disease severity and disease duration. METHODS: The sample consisted of 116 consecutive people with MS (response rate: 75.8%; 72.4% women; mean age 40.3 +/- 9.8). People with MS completed the Short-Form Health Survey (SF-36) for measuring PCS and MCS and the Participation Scale, which measures the level of social participation. Disability was assessed using the Expanded Disability Status Scale (EDSS). The associations between social participation, PCS and MCS, were analyzed using linear regression that controlled for sociodemographic and clinical variables. RESULTS: PCS was significantly associated with age, disease duration, EDSS and social participation. MCS did not show significant association with the studied variables. Overall, a multiple regression model explained 48% of the PCS variance, while the proportion of MCS variance explained was not significant. CONCLUSIONS: Social participation was significantly associated with PCS, suggesting a possibility for intervention in this domain. PMID- 25130597 TI - A nationwide population-based cohort study on tonsillectomy and subsequent cancer incidence. AB - OBJECTIVES/HYPOTHESIS: Tonsillectomy is related to increased risk of certain types of cancer. This study evaluates the possible association between tonsillectomy and cancer in Taiwan. METHODS: Data from the National Health Insurance system of Taiwan was used. A cohort study consisting of 997 patients with a new diagnosis of tonsillectomy from 2000 to 2005 and a comparison cohort of 3,988 subjects without tonsillectomy were used in the Poisson regression analysis to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of cancers. RESULTS: The incidence rate of all cancer types was higher in the tonsillectomy group than in the control group (4.28 vs. 2.97 per 1,000 person-years, respectively), with an IRR = 1.54 and 95% CI of 1.05 to 2.25, but the significant difference was limited to patients with more than 3 years follow-up. Site-specific analysis found no significant association between tonsillectomy and any individual cancer after adjusting for age, sex, hyperlipidemia, hypertension, and diabetes; however, tonsillectomy patients with more than 3 years follow-up had a marginally significantly higher risk for breast cancer development (adjusted IRR = 2.62; CI = 0.97-7.03). CONCLUSION: Our study found that Taiwanese people with tonsillectomy have a significantly higher overall risk of developing cancer and a marginally higher risk of developing breast cancer when follow-up is longer than 3 years. PMID- 25130598 TI - Nursing educators' perceptions about disaster preparedness and response in Istanbul and Miyazaki. AB - AIM: As healthcare professionals, nursing educators need to be prepared to manage and deliver care in what are often dangerous conditions. This research aims to determine and compare nursing educators' perceptions of disaster preparedness and response (DP&R) in Istanbul and Miyazaki. METHODS: An 18 question descriptive questionnaire was used. RESULTS: One hundred and forty-four nursing educators representing two state university nursing schools in Istanbul, Turkey, and one state and two private universities in Miyazaki, Japan were enrolled. Educators had an average age of 40 years and had been educators for 1-15 years. Just over half of the participants had basic knowledge regarding DP&R with most of them considering taking special courses in the future. The majority considered "caregiver" as a role they could undertake in a disaster situation. The existence of major concerns and conflicts in disaster responses were low. The top ranked item was in the area of conflict between family and job responsibilities. Age and academic levels showed significant differences in basic knowledge on DP&R. Regardless of knowledge in this subject area, no statistical significance on personal preparedness or being a volunteer to disaster events was found. CONCLUSION: Nursing educators were not thinking about what kinds of disasters occur in the areas where they currently teach and were underprepared to deal with disaster situations. To improve the perceptions of the nursing educators on DP&R, mass casualty care and disaster management skills need to be incorporated into formal education and training on disaster preparedness and workplace preparedness. PMID- 25130599 TI - A general overview of the organocatalytic intramolecular aza-Michael reaction. AB - The organocatalytic intramolecular aza-Michael reaction gives access to enantiomerically enriched nitrogen-containing heterocycles in a very simple manner. Enals, enones, conjugated esters and nitro olefins have been employed as Michael acceptors, while moderate nitrogen nucleophiles such as sulphonamides, carbamates and amides have been shown to be appropriate Michael donors in this type of reaction. Additionally, the process has been performed under both covalent and non-covalent catalysis, with diaryl prolinols, imidazolidinones, thioureas and chiral binol phosphoric acids being the most frequently used catalysts. The level of efficiency reached with this protocol is demonstrated by the implementation of numerous tandem processes, as well as the total synthesis of several natural products. PMID- 25130600 TI - Fabrication of ultralong hybrid microfibers from nanosheets of reduced graphene oxide and transition-metal dichalcogenides and their application as supercapacitors. AB - Two-dimensional materials have attracted increasing research interest owing to their unique electronic, physical, optical, and mechanical properties. We thus developed a general strategy for the fabrication of ultralong hybrid microfibers from a mixture of reduced graphene oxide and transition-metal dichalcogenides (TMDs), including MoS2 , TiS2 , TaS2 , and NbSe2 . Furthermore, we prepared fiber based solid-state supercapacitors as a proof-of-concept application. The performance of thus-prepared supercapacitors was greatly improved by the introduction of the TMDs. PMID- 25130601 TI - Molecular pathology in lung cancer: a guide to the techniques used in clinical practice. AB - Five year survival rates for lung cancer patients are poor; however the development of new therapeutic options, which benefit subsets of the population, offer hope of improvement. These novel therapies frequently rely upon the analysis of biomarkers in pathology samples; in lung cancer patients, testing is now routinely carried out to identify small mutations and chromosomal rearrangements in order to predict response to treatment. The recent increase in biomarker analyses in pathology samples has lead to the development of a new specialty, molecular pathology. The use of molecular pathology assays in clinical samples is largely under the control of the histopathologist; who is likely to be asked, as a minimum, to select tissue sections for molecular analysis and mark areas of H&E stained slides for macro or microdissection. Many histopathologists will also be involved in the sourcing and implementation of new assays. This review aims to provide a guide to some of the most commonly used molecular pathology methods - their advantages and their limitations. PMID- 25130603 TI - The STRONGkids nutritional risk screening tool can be used by paediatric nurses to identify hospitalised children at risk. AB - AIM: Hospitalised children have higher rates of undernutrition. Early detection of at-risk patients could lead to prompt preventative or corrective interventions. Several nutritional risk screening tools are available for screening hospitalised children including the STRONGkids tool. This study was designed to assess the usefulness of STRONGkids when applied by nurses rather than a paediatrician. METHODS: The STRONGkids questionnaire was simplified to enhance clarity with nursing staff. Trained nursing staff were asked to apply the tool to children, aged 1 month to 17 years, admitted to the Christchurch Hospital, New Zealand. Each patient was also assessed by a paediatrician. In addition, the current nutritional state of each patient was defined by measuring their weight and height. RESULTS: Of the 162 children enrolled, 11.7% were undernourished and 13% overnourished. STRONGkids recognised 84% of undernourished children when the tool was applied by nurses and 90% when the tool was applied by a paediatrician, indicating substantial agreement (kappa = 0.65). A minor simplification to the questionnaire improved its utility. CONCLUSION: STRONGkids successfully recognised at-risk children, when applied by either nurses or a paediatrician. It was suitable and feasible for nursing staff to use it to screen for children at risk of nutritional deterioration. PMID- 25130602 TI - Risk factors for major adverse events late after Fontan palliation. AB - OBJECTIVE: Risk factors for major adverse events late after Fontan palliation are unknown. Prior studies have suggested ventricular function and morphology as important risk factors. The aim of this study is to (1) characterize the late major adverse event profile in adult Fontan patients and (2) identify additional risk factors that may contribute to adverse outcomes. DESIGN AND SETTING: A retrospective review of all adult patients >15 years post-Fontan seen at a tertiary academic center was conducted. Clinical, laboratory, cardiac data, and abdominal imaging were collected via chart review. Major adverse events (death, cardiac transplantation, or listing) were identified, and timing of events was plotted using Kaplan-Meier methods. Univariate and multivariate logistic regression was used to determine independent predictors of late-term events. RESULTS: A total of 123 adult Fontan patients were identified (mean time post Fontan 22.4 years [+/-4.4]). Major adverse events occurred in 19/123 patients (15%). In this 15-year survivor cohort, transplant-free survival rates were 94.6%, 82.9%, and 59.8% at 20, 25, and 30 years postoperation, respectively. Modes of death were Fontan failure with preserved function (4), congestive heart failure with decreased function (2), sudden death (2), thromboembolic event (1), post-Fontan conversion (2), and posttransplant (2). No differences in adverse outcomes were found based on morphology of the systemic ventricle, Fontan type, or systolic ventricular function. On the other hand, features of portal hypertension (OR 19.0, CI 4.7-77.3, P < .0001), presence of a pacemaker (OR 13.4, CI 2.6-69.8, P = .002), and systemic oxygen desaturation (OR 0.86, CI 0.75-0.98, P = .02) were risk factors for major adverse events in the multivariate analysis. CONCLUSIONS: In adult Fontan patients surviving >15 years post-Fontan, portal hypertension, oxygen desaturation, and need for pacemaker were predictive of adverse events. Traditional measures may not predict late-term outcomes in adult survivors; further study of the liver's role in late outcomes is warranted. PMID- 25130604 TI - Aptamers as drug delivery vehicles. AB - The benefits of directed and selective therapy for systemic treatment are reasons for increased interest in exploiting aptamers for cell-specific drug delivery. Nucleic acid based pharmaceuticals represent an interesting and novel tool to counter human diseases. Combining inhibitory potential and cargo transfer upon internalization, nanocarriers as well as various therapeutics including siRNAs, chemotherapeutics, photosensitizers, or proteins can be imported via these synthetic nucleic acids. However, widespread clinical application is still hampered by obstacles that must be overcome. In this review, we give an overview of applications and recent advances in aptamer-mediated drug delivery. We also introduce prominent selection methods as well as useful approaches in choice of drug and conjugation method. We discuss the challenges that need to be considered and present strategies that have been applied to achieve intracellular delivery of effectors transported by readily internalized aptamers. PMID- 25130605 TI - Predonation screening of candidate donors and prevention of window period donations. AB - BACKGROUND: Infectious window period donations slip through routine donor screening procedures. To explore the potential value of predonation screening of candidate donors, we compared the proportion of incident transfusion transmissible infections in candidate donors, in first-time donors, and in repeat donors. STUDY DESIGN AND METHODS: A retrospective analysis was performed of all incident hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections in candidate, first-time, and repeat donors in the Netherlands during the period 2009 to 2013. RESULTS: In total, 176,716 candidate donors, 144,226 first-time donations, and 4,143,455 repeat donations were screened for HBV, HCV, and HIV infection. Acute HBV infection was identified in the predonation sample of six candidate donors. One first-time donor, testing HIV-negative at predonation screening, tested positive for anti HIV and HIV RNA in the first donation 29 days later. Among repeat donations we identified 15, one, and six incident HBV, HCV and HIV infections, respectively. The proportion of incident infections among candidate donors/first-time donations/repeat donations was for HBV, 3.40/0/0.36; for HCV, 0/0/0.02; and for HIV 0/0.69/0.14 per 100,000, respectively. CONCLUSION: Predonation screening of candidate donors very likely causes a loss of donations, but it might prevent undetected window period donations. Further studies are necessary to determine the value of predonation screening as an additional safety measure. PMID- 25130606 TI - THP-1 cell line: an in vitro cell model for immune modulation approach. AB - THP-1 is a human leukemia monocytic cell line, which has been extensively used to study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient and drug transport. This cell line has become a common model to estimate modulation of monocyte and macrophage activities. This review attempts to summarize and discuss recent publications related to the THP-1 cell model. An overview on the biological similarities and dissimilarities between the THP-1 cell line and human peripheral blood mononuclear cell (PBMC) derived-monocytes and macrophages, as well as the advantages and disadvantages of the use of THP-1 cell line, is included. The review summarizes different published co-cultivation studies of THP-1 cells with other cell types, for instance, intestinal cells, adipocytes, T-lymphocytes, platelets, and vascular smooth muscle cells, which can be an option to study cell-cell interaction in vitro and can be an approach to better mimic in vivo conditions. Macrophage polarization is a relatively new topic which gains interest for which the THP-1 cell line also may be relevant. Besides that an overview of newly released commercial THP-1 engineered-reporter cells and THP-1 inflammasome test-cells is also given. Evaluation of recent papers leads to the conclusion that the THP-1 cell line has unique characteristics as a model to investigate/estimate immune-modulating effects of compounds in both activated and resting conditions of the cells. Although the THP 1 response can hint to potential responses that might occur ex vivo or in vivo, these should be, however, validated by in vivo studies to draw more definite conclusions. PMID- 25130607 TI - Prolonged pretreatment of mice with cholera toxin, but not isoproterenol, alleviates acute lethal systemic inflammatory response. AB - Isoproterenol, a synthetic non-selective beta-adrenergic agonist, is often used during the immediate postoperative period after open heart surgery for its chronotropic and vasodilatory effects. It has been demonstrated that isoproterenol pretreatment followed by immediate LPS administration leads to reduced tumor necrosis factor-alpha (TNF-alpha) response in vivo. However, sepsis never happens immediately after the surgery, but rather severe immune dysfunction occurs at least 24h later. It remains elusive what effects isoproterenol might exert to innate immunity during the period. In this scenario, we investigated the effects of 24-h isoproterenol pretreatment on septic shock induced by experimental endotoxemia and bacterial peritonitis, with cholera toxin as another cAMP elevator. Unexpectedly, we found that isoproterenol and cholera toxin exhibited distinct effects in acute lethal systemic inflammatory response. Isoproterenol worsened liver injury without enhancing NK/NKT activity. Meanwhile, cholera toxin but not isoproterenol showed dramatically reduced TNF-alpha response in LPS induced septic shock. Our data provide a caution for the clinical use of isoproterenol and suggest that isoproterenol has cAMP-independent functions. PMID- 25130608 TI - All trans-retinoic acid abrogates the pro-tumorigenic phenotype of prostate cancer tumor-associated macrophages. AB - Tumor-associated macrophages (TAMs) are a prominent cell type of the tumor stroma and stimulate malignant cell growth, survival and metastasis. The present manuscript demonstrates that prostate cancer cell-derived factors induce a pro tumoral TAM-like phenotype characterized by increased proliferation and increased expression of pro-angiogenic, immunosuppressive and pro-metastatic factors. These effects were abrogated by all trans-retinoic acid (ATRA), a clinically available molecule with known immune-modulating properties. Furthermore, ATRA inhibited the cancer cell-stimulated proliferation of the pro-tumoral macrophages and restored their cytotoxic capacity towards prostate cancer cells. These findings suggest the use of ATRA as an immunomodulating agent to block the activity of prostate cancer TAMs. PMID- 25130610 TI - Shared genetic risk factors for psychiatric illness. PMID- 25130609 TI - "Celtic migrations": fact or fiction? Strontium and oxygen isotope analysis of the Czech cemeteries of Radovesice and Kutna Hora in Bohemia. AB - Strontium and oxygen isotope analysis of human remains from the early La Tene (fourth/third century BC) Czech cemeteries of Radovesice I (RAD I), Radovesice II (RAD II), and Kutna Hora were conducted to investigate the importance of residential changes during the period of the historic "Celtic migrations". In the initial phases (LT A/B), the grave goods of these cemeteries are typical for the core area of the La Tene culture, while around 300 BC (LT B2) an alteration occurs and typical Bohemian styles arise, and connections to Moravia and the Danubian region become visible. The strontium isotope ratios are highly varied with (87) Sr/(86) Sr values between 0.7062 and 0.7153 in Radovesice, and between 0.7082 and 0.7147 in Kutna Hora. The oxygen isotope data are more homogeneous and yield delta(18) Op ratios from 14.80/00 to 17.20/00 [mean: 16.20/00 +/- 0.5 (1sigma)] in Radovesice, and from 14.90/00 to 17.30/00 [mean: 16.50/00 +/- 0.6 (1sigma)] in Kutna Hora. Because the geological properties of the landscapes around the sites are variable and complex, most of the observed variations among the strontium isotope ratios may have been caused by agricultural practices, such as regularly changing farming land. Nevertheless, there are some individuals who differ completely from the regional isotopic baseline values. This suggests that at least a small part of the community migrated, which does not seem to be correlated with any particular phase of the La Tene period. Remarkably, it is mainly males who seem to be of nonlocal origin, and particularly those who were buried as warriors. Females, on the other hand, appear to have been more closely bonded to the Bohemian region. Whether the "foreign" individuals with differing isotopic compositions came from Moravia or the Danubian region remains debatable. PMID- 25130611 TI - Der p 2 can induce bystander activation of B cells derived from patients with systemic lupus erythematosus. AB - Although many patients with SLE also have allergies, the immunological events triggering the onset and progression of the clinical manifestations of SLE by allergens have yet to be clarified. A total of three autoantigens, phosphoglycerate kinase 1 (PGK-1), triosephosphate isomerase (TIM) and enolase were identified by autologous serum in B cell lysate derived from HDM allergic SLE patients after Der p 2 stimulation. Autoantigen, TRIM-21 expression were also significantly increased in B cells derived from HDM allergic SLE patients. In PBMCs derived from SLE patients, the concentration of anti-PGK-1 was significantly upregulated after Der p 2 stimulation compared to HDM allergic without SLE patients and healthy subjects. Inflammatory related cytokines and chemokines include IL-1beta, IL-6, IL-8, CXCL5 could be upregulated after Der p 2 stimulation in PBMCs derived from HDM allergic SLE patients. In conclusion, our data demonstrated that long-term allergen exposure could be a contributing factor in the development of SLE. PMID- 25130612 TI - Efficacy analysis of tyrosine kinase inhibitors on rare non-small cell lung cancer patients harboring complex EGFR mutations. AB - The efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKI) in patients with non-small cell lung cancer (NSCLC) is related to EGFR mutations. Although the p.L858R point mutation in exon 21 and the in-frame deletion mutation in exon 19 are well known, efficacy of EGFR-TKI in patients with more than one EGFR mutation is not well understood. 799 NSCLC patients were screened for EGFR mutations. Of the 799 patients, 443 (55.4%) had mutations, out of which 22 (2.75%) had multiple complex mutations. Most multiple mutations (20/22) harbored common mutations such as the p.L858R point mutation in exon 21 and the in-frame deletion mutation in exon 19. 11 out of 22 patients who had multiple EGFR mutations underwent TKI therapy and primary end-points of progression free and overall survival were determined. Our analysis revealed that cases with multiple mutations had similar end-point outcomes as single mutation to TKI therapy. Report of these cases will be helpful in decision making for treatment of NSCLC patients harboring multiple EGFR mutations. PMID- 25130613 TI - Carbamylation of immunoglobulin abrogates activation of the classical complement pathway. AB - Post-translational modifications of proteins significantly affect their structure and function. The carbamylation of positively charged lysine residues to form neutral homoitrulline occurs primarily under inflammatory conditions through myeloperoxidase-dependent cyanate (CNO-) formation. We analyzed the pattern of human IgG1 carbamylation under inflammatory conditions and the effects that this modification has on the ability of antibodies to trigger complement activation via the classical pathway. We found that the lysine residues of IgG1 are rapidly modified after brief exposure to CNO- . Interestingly, modifications were not random, but instead limited to only few lysines within the hinge area and the N terminal fragment of the CH2 domain. A complement activation assay combined with mass spectrometry analysis revealed a highly significant inverse correlation between carbamylation of several key lysine residues within the hinge region and N-terminus of the CH2 domain and the proper binding of C1q to human IgG1 followed by subsequent complement activation. This severely hindered complement-dependent cytotoxicity of therapeutic IgG1 . The reaction can apparently occur in vivo, as we found carbamylated antibodies in synovial fluid from rheumatoid arthritis patients. Taken together, our data suggest that carbamylation has a profound impact on the complement-activating ability of IgG1 and reveals a pivotal role for previously uncharacterized lysine residues in this process. PMID- 25130614 TI - Mutation of Dcdc2 in mice leads to impairments in auditory processing and memory ability. AB - Dyslexia is a complex neurodevelopmental disorder characterized by impaired reading ability despite normal intellect, and is associated with specific difficulties in phonological and rapid auditory processing (RAP), visual attention and working memory. Genetic variants in Doublecortin domain-containing protein 2 (DCDC2) have been associated with dyslexia, impairments in phonological processing and in short-term/working memory. The purpose of this study was to determine whether sensory and behavioral impairments can result directly from mutation of the Dcdc2 gene in mice. Several behavioral tasks, including a modified pre-pulse inhibition paradigm (to examine auditory processing), a 4/8 radial arm maze (to assess/dissociate working vs. reference memory) and rotarod (to examine sensorimotor ability and motor learning), were used to assess the effects of Dcdc2 mutation. Behavioral results revealed deficits in RAP, working memory and reference memory in Dcdc2(del2/del2) mice when compared with matched wild types. Current findings parallel clinical research linking genetic variants of DCDC2 with specific impairments of phonological processing and memory ability. PMID- 25130616 TI - Soil as a source of Legionella pneumophila sequence type 47. AB - Legionella pneumophila sequence type (ST) 47 was isolated from soil in a garden. We speculate that this strain was transmitted from soil to the whirlpool in the garden where it caused an outbreak of Legionnaires' disease and Pontiac fever. In the Netherlands, ST47 is frequently isolated from patients, but hardly ever from environmental sources. It is possible that human pathogenic Legionella strains, with ST47 as one of the predominant strains, are transmitted to humans from sources such as natural soil that are currently not targeted in outbreak investigations. PMID- 25130615 TI - Bone regeneration with osteogenically enhanced mesenchymal stem cells and their extracellular matrix proteins. AB - Although bone has remarkable regenerative capacity, about 10% of long bone fractures and 25% to 40% of vertebral fusion procedures fail to heal. In such instances, a scaffold is employed to bridge the lesion and accommodate osteoprogenitors. Although synthetic bone scaffolds mimic some of the characteristics of bone matrix, their effectiveness can vary because of biological incompatibility. Herein, we demonstrate that a composite prepared with osteogenically enhanced mesenchymal stem cells (OEhMSCs) and their extracellular matrix (ECM) has an unprecedented capacity for the repair of critical-sized defects of murine femora. Furthermore, OEhMSCs do not cause lymphocyte activation, and ECM/OEhMSC composites retain their in vivo efficacy after cryopreservation. Finally, we show that attachment to the ECM by OEhMSCs stimulates the production of osteogenic and angiogenic factors. These data demonstrate that composites of OEhMSCs and their ECM could be utilized in the place of autologous bone graft for complex orthopedic reconstructions. PMID- 25130617 TI - Efficacy of real-time polymerase chain reaction for rapid diagnosis of endobronchial tuberculosis. AB - OBJECTIVES: The definitive diagnosis of endobronchial tuberculosis (EBTB) is challenging because the disease manifests in various non-specific ways, and acid fast bacilli (AFB) are often undetectable by sputum smear. The objective of this study was to evaluate the efficacy of real-time PCR of bronchoscopic biopsy specimens for the diagnosis of EBTB. METHODS: Real-time PCR amplification of Mycobacterium tuberculosis DNA in biopsy tissue from EBTB patients was performed prospectively. Diagnostic yields were compared for real-time PCR and for auramine O-stained sputum smears and bronchial brush smears. Whether diagnostic yield depended on bronchoscopic subtype of EBTB was also evaluated. RESULTS: Diagnostic yields were 4.1% (3/74) for sputum smear, 39.2% (29/74) for bronchial brush smear, and 89.2% (66/74) for real-time PCR. Real-time PCR melting curve analysis showed significantly higher yields than did AFB staining of bronchial brush smears for granular and caseating EBTB (p<0.01). CONCLUSIONS: Real-time PCR detection of M. tuberculosis DNA in EBTB biopsy tissue is more sensitive than sputum smear and bronchial brush smear, including at early disease stages. This PCR method may be a useful adjunct to culture- and smear-based techniques to allow more rapid EBTB diagnosis and timelier treatment. PMID- 25130618 TI - Xylan-mediated aggregation of Lactobacillus brevis and its relationship with the surface properties and mucin-mediated aggregation of the bacteria. AB - Some Lactobacillus brevis strains were found to aggregate upon the addition of xylan after screening for lactic acid bacteria that interact with plant materials. The S-layer proteins of cell surface varied among the strains. The strains that displayed xylan-mediated aggregation retained its ability even after the removal of S-layer proteins. L. brevis had negative zeta potentials. A correlation between the strength of aggregation and zeta potential was not observed. However, partial removal of S-layer proteins resulted in decreases in the electric potential and aggregation ability of some strains. Therefore, xylan mediated aggregation of L. brevis was considered to be caused by an electrostatic effect between the cells and xylan. L. brevis also aggregated in the presence of mucin, and the strengths of aggregation among the strains were similar to that induced by xylan. Thus, xylan- and mucin-mediated L. brevis aggregation was supposed to be caused by a similar mechanism. PMID- 25130619 TI - Calculating core-level excitations and X-ray absorption spectra of medium-sized closed-shell molecules with the algebraic-diagrammatic construction scheme for the polarization propagator. AB - Core-level excitations are generated by absorption of high-energy radiation such as X-rays. To describe these energetically high-lying excited states theoretically, we have implemented a variant of the algebraic-diagrammatic construction scheme of second-order ADC(2) by applying the core-valence separation (CVS) approximation to the ADC(2) working equations. Besides excitation energies, the CVS-ADC(2) method also provides access to properties of core-excited states, thereby allowing for the calculation of X-ray absorption spectra. To demonstrate the potential of our implementation of CVS-ADC(2), we have chosen medium-sized molecules as examples that have either biological importance or find application in organic electronics. The calculated results of CVS-ADC(2) are compared with standard TD-DFT/B3LYP values and experimental data. In particular, the extended variant, CVS-ADC(2)-x, provides the most accurate results, and the agreement between the calculated values and experiment is remarkable. PMID- 25130620 TI - Alpine climate treatment of atopic dermatitis: a systematic review. AB - Climate therapy has been used for decades in the treatment of atopic dermatitis (AD), but evidence of its effectiveness has not yet been assessed systematically. A systematic literature search in Medline, Embase, and the Cochrane library was performed to identify all original studies concerning alpine climate treatment. The risk of bias of individual studies was assessed following the Cochrane Handbook, and level of evidence was rated using GRADE guidelines. Fifteen observational studies were included concerning 40 148 patients. Four studies concerning 2670 patients presented follow-up data over a period of 1 year. Disease activity decreased in the majority of patients during treatment (96% of n = 39 006) and 12-month follow-up (64% of n = 2670). Topical corticosteroid use could often be reduced or stopped during treatment (82% of n = 1178) and during 12-month follow-up (72% of n = 3008). Quality assessment showed serious study limitations, therefore resulting in a very low level of evidence for the described outcomes. Randomized controlled trials designed with a follow-up period including well-defined patient populations, detailed description and measurement of applied interventions during climate therapy and using validated outcomes including cost-effectiveness parameters, are required to improve the evidence for alpine climate therapy as an effective treatment for patients with AD. PMID- 25130621 TI - Blockade of monoacylglycerol lipase inhibits oligodendrocyte excitotoxicity and prevents demyelination in vivo. AB - The endocannabinoids 2-araquidonoylglycerol (2-AG) and anandamide (AEA) are bioactive lipids crucially involved in the regulation of brain function in basal and pathological conditions. Blockade of endocannabinoid metabolism has emerged as a promising therapeutic strategy for inflammatory diseases of the central nervous system, including myelin disorders such as multiple sclerosis. Nevertheless, the biological actions of endocannabinoid degradation inhibitors in oligodendrocytes and white matter tracts are still ill defined. Here we show that the selective monoacylglycerol lipase (MAGL) inhibitor JZL184 suppressed cell death by mild activation of AMPA receptors in oligodendrocytes in vitro, an effect that was mimicked by MAGL substrate 2-AG and by the second major endocannabinoid AEA, in a concentration-dependent manner, whereas inhibition of the AEA metabolizing enzyme fatty acid amide hydrolase with URB597 was devoid of effect. Pharmacological experiments suggested that oligodendrocyte protection from excitotoxicity resulting from MAGL blockade involved the activation of cannabinoid CB1 receptors and the reduction of AMPA-induced cytosolic calcium overload, mitochondrial membrane depolarization, and production of reactive oxygen species. Administration of JZL184 under a therapeutic regimen decreased clinical severity, prevented demyelination, and reduced inflammation in chronic experimental autoimmune encephalomyelitis. Furthermore, MAGL inactivation robustly preserved myelin integrity and suppressed microglial activation in the cuprizone-induced model of T-cell-independent demyelination. These findings suggest that MAGL blockade may be a useful strategy for the treatment of immune dependent and -independent damage to the white matter. PMID- 25130622 TI - Supine or sitting? Economic considerations regarding patient position during plasma metanephrine analysis for the exclusion of chromaffin tumours. PMID- 25130623 TI - Improving acid-fast fluorescent staining for the detection of mycobacteria using a new nucleic acid staining approach. AB - Acid fast staining of sputum smears by microscopy remains the prevalent method for detecting Mycobacterium tuberculosis. The sensitivity of microscopy using acid fast stains requires 10(4) bacilli per ml of sputum. Although fluorescent acid fast stains, such as Auramine-O, show improved sensitivity, almost half of culture-positive TB cases are currently estimated to remain smear-negative. These current diagnosis problems provide impetus for improving staining procedures. We evaluated a novel fluorescent acid-fast staining approach using the nucleic acid binding dye SYBR((r)) Gold on mycobacterial in vitro cultures. The SYBR((r)) Gold stain detected 99% of MTB in both actively replicating aerobic and non replicating hypoxic cultures. Transmission light microscopy with Ziehl-Neelsen fuchsin, and fluorescence microscopy with Auramine-O or Auramine-rhodamine detected only 54%-86% of MTB bacilli. SYBR((r)) Gold fluoresces more intensely than Auramine-O, and is highly resistant to fading. The signal to noise ratio is exceptionally high due to a >1000-fold enhanced fluorescence after binding to DNA/RNA, thereby reducing most background fluorescence. Although cost and stability of the dye may perhaps limit its clinical use at this time, these results warrant further research into more nucleic acid dye variants. In the meantime, SYBR((r)) Gold staining shows great promise for use in numerous research applications. PMID- 25130624 TI - Biogeochemical environments of streambed-sediment pore waters with and without arsenic enrichment in a sedimentary rock terrain, New Jersey Piedmont, USA. AB - Release of arsenic (As) from sedimentary rocks has resulted in contamination of groundwater in aquifers of the New Jersey Piedmont Physiographic Province, USA; the contamination also may affect the quality of the region's streamwater to which groundwater discharges. Biogeochemical mechanisms involved in the release process were investigated in the streambeds of Six Mile Run and Pike Run, tributaries to the Millstone River in the Piedmont. At Six Mile Run, streambed pore water and shallow groundwater were low or depleted in oxygen, and contained As at concentrations greater than 20 MUg/L. At Pike Run, oxidizing conditions were present in the streambed, and the As concentration in pore water was 2.1 MUg/L. The 16S rRNA gene and the As(V) respiratory reductase gene, arrA, were amplified from DNA extracted from streambed pore water at both sites and analyzed, revealing that distinct bacterial communities that corresponded to the redox conditions were present at each site. Anaerobic enrichment cultures were inoculated with pore water from gaining reaches of the streams with acetate and As(V). As(V) was reduced by microbes to As(III) in enrichments with Six Mile Run pore water and groundwater, whereas no reduction occurred in enrichments with Pike Run pore water. Cloning and sequencing of the arrA gene indicated 8 unique operational taxonomic units (OTUs) at Six Mile Run and 11 unique OTUs at Pike Run, which may be representative of the arsenite oxidase gene arxA. Low-oxygen conditions at Six Mile Run have favored microbial As reduction and release, whereas release was inhibited by oxidizing conditions at Pike Run. PMID- 25130625 TI - Comparison of three pesticide fate models with respect to the leaching of two herbicides under field conditions in an irrigated maize cropping system. AB - The ability of three models (PEARL, MACRO and PRZM) to describe the water transfer and leaching of the herbicides S-metolachlor and mesotrione as observed in an irrigated maize monoculture system in Toulouse area (France) was compared. The models were parameterized with field, laboratory and literature data, and pedotransfer functions using equivalent parameterization to better compare the results and the performance of the models. The models were evaluated and compared from soil water pressure, water content and temperature data monitored at 0.2, 0.5 and 1 m depth, together with water percolates and herbicide concentrations measured in a tension plate lysimeter at 1 m depth. Some hydraulic (n, theta(s)) parameters and mesotrione DT50 needed calibration. After calibration, the comparison of the results obtained by the three models indicated that PRZM was not able to simulate properly the water dynamic in the soil profile. On the contrary, PEARL and MACRO simulated generally quite well the observed water pressure head and volumetric water content at the three different depths during wetting periods (e.g. irrigated cropping period) while a poorest performance was obtained for drying periods (fallow period with bare soil and beginning of crop period). Similar water flow dynamics were simulated by PEARL and MACRO in the soil profile although in general, and due to a higher evapotranspiration in MACRO, PEARL simulated a wetter soil than MACRO. For the whole simulated period, the performance of all models to simulate water leaching at 1m depth was poor, with an overestimation of the total water volume measured in the lysimeter (ranging from 2.2 to 6.6 times). By contrast, soil temperature was properly reproduced by the three models. The models were able to simulate the leaching of herbicides at 1m depth in similar appearance time and order of magnitude as field observations. Cumulative observed and simulated mesotrione losses by leaching were consistently higher than the observed and simulated losses of the less mobile herbicide, S-metolachlor. In general, PRZM predicted the highest concentrations for both herbicides in the leachates while PEARL simulated the observed herbicide concentrations better than MACRO and PRZM. PMID- 25130626 TI - Over the sands and far away: interpreting an Iberian mitochondrial lineage with ancient Western African origins. AB - OBJECTIVES: There is an ongoing effort to characterize the genetic links between Africa and Europe, mostly using lineages and haplotypes that are specific to one continent but had an ancient origin in the other. Mitochondrial DNA has been proven to be a very useful tool for this purpose since a high number of putatively European-specific variants of the African L* lineages have been defined over the years. Due to their geographic locations, Spain and Portugal seem to be ideal places for searching for these lineages. METHODS: Five members of a minor branch of haplogroup L3f were found in recent DNA samplings in the region of Asturias (Northern Spain), which is known for its historical isolation. The frequency of L3f in this population (~1%) is unexpectedly high in comparison with other related lineages in Europe. Complete mitochondrial DNA sequencing of these L3f lineages, as well phylogenetic and phylogeographic comparative analyses have been performed. RESULTS: The L3f variant found in Asturias seems to constitute an Iberian-specific haplogroup, distantly related to lineages in Northern Africa and with a deep ancestry in Western Africa. Coalescent algorithms estimate the minimum arrival time as 8,000 years ago, and a possible route through the Gibraltar Strait. CONCLUSIONS: Results are concordant with a previously proposed Neolithic connection between Southern Europe and Western Africa, which might be key to the proper understanding of the ancient links between these two continents. PMID- 25130627 TI - The mitochondrial genome of Paragyrodactylus variegatus (Platyhelminthes: Monogenea): differences in major non-coding region and gene order compared to Gyrodactylus. AB - BACKGROUND: Paragyrodactylus Gvosdev and Martechov, 1953, a viviparous genus of ectoparasite within the Gyrodactylidae, contains three nominal species all of which infect Asian river loaches. The group is suspected to be a basal lineage within Gyrodactylus Nordmann, 1832 sensu lato although this remains unclear. Further molecular study, beyond characterization of the standard Internal Transcribed Spacer region, is needed to clarify the evolutionary relationships within the family and the placement of this genus. METHODS: The mitochondrial genome of Paragyrodactylus variegatus You, King, Ye and Cone, 2014 was amplified in six parts from a single worm, sequenced using primer walking, annotated and analyzed using bioinformatic tools. RESULTS: The mitochondrial genome of P. variegatus is 14,517 bp, containing 12 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes and a major non-coding region (NCR). The overall A + T content of the mitochondrial genome is 76.3%, which is higher than all reported mitochondrial genomes of monogeneans. All of the 22 tRNAs have the typical cloverleaf secondary structure, except tRNACys, tRNASer1 and tRNASer2 that lack the dihydrouridine (DHU) arm. There are six domains (domain III is absent) and three domains in the inferred secondary structures of the large ribosomal subunit (rrnL) and small ribosomal subunit (rrnS), respectively. The NCR includes six 40 bp tandem repeat units and has the double identical poly-T stretches, stem-loop structure and some surrounding structure elements. The gene order (tRNAGln, tRNAMet and NCR) differs in arrangement compared to the mitochondrial genomes reported from Gyrodactylus spp. CONCLUSION: The Duplication and Random Loss Model and Recombination Model together are the most plausible explanations for the variation in gene order. Both morphological characters and characteristics of the mitochondrial genome support Paragyrodactylus as a distinct genus from Gyrodactylus. Considering their specific distribution and known hosts, we believe that Paragyrodactylus is a relict freshwater lineage of viviparous monogenean isolated in the high plateaus of central Asia on closely related river loaches. PMID- 25130628 TI - Marked Elevation of Excitatory Amino Acids in Cerebrospinal Fluid Obtained From Patients With Rotavirus-Associated Encephalopathy. AB - Rotavirus is the most common cause of severe gastroenteritis in young children; however, its pathogenesis and immunity are not completely understood. Even less well recognized is rotavirus-induced central nervous system (CNS) involvement, which has been associated with seizure, encephalopathy and death, among others. To elucidate the host response to rotavirus infection, we retrospectively examined neurotransmitter amino acids in the cerebrospinal fluid (CSF) of 19 children with CNS involvement associated with rotavirus infection. Subjects were classified into two groups: those with encephalopathy followed by prolonged seizure (encephalopathy group) and those who had experienced afebrile, brief cluster of seizures without encephalopathy (cluster group). The levels of glutamate, glycine, and taurine in the encephalopathy group were significantly higher than those in the cluster group. Increased levels of excitatory amino acids in the CSF may induce neurological disorders and be related to disorder severity. To the best of our knowledge, this is the first report regarding amino acids in the CSF obtained from patients with rotavirus-induced CNS involvement. Further study is necessary to elucidate the role of CSF amino acid levels in rotavirus-induced CNS involvement. PMID- 25130629 TI - [Effect of the liquid milk nutritional supplement with enhanced content of whey protein on the nutritional status of the elderly]. AB - AIM: The aim of this study was to evaluate the effect of long-term administration of liquid nutritional supplement with increased amounts of whey protein and reduced amounts of lactose, produced in accordance with a new recipe "Nutrisen" on the elderly living in institutionalized care. METHODS: The study was carried out from May to July, 2013, on 47 retirement home residents, living in Prague, all of which were 65 years or older. Supplemented group (n = 23) consumed (200 ml) milk drinks with three different flavours on a daily basis for eight weeks. The reference group was on a normal diet. There was no significant difference in baseline characteristics between participants in both groups. Anthropometric and biochemical indicators of nutritional status and tolerance of the nutritional supplement during long-term use were evaluated. RESULTS: Both compliance (daily intake program) and tolerance of the nutritionally defined supplement were very good. For the supplemented group, there was an average weight increased of 700 grams after the 8 week nutritional supplement test period. Average levels of albumin and prealbumin increased significantly (from the beginning to the end of the program), 35.5 +/- 4.52 g/l vs 36.19 +/- 4.1 g/l and 0.160 +/- 0.05 vs 0.174 +/- 0.04 g/l (p < 0.05), vitamin D levels increased from 31.2 +/- 16.4 nmol/l to 36.8 +/- 17.7 nmol/l (p < 0.001) and HDL-cholesterol levels increased from 1.29 +/- 0.33 mmol/l to 1.35 +/- 0.35 mmol/l (p < 0.001). CONCLUSION: The specific nutritionally defined milk drink (Nutrisen), used in this study, was well tolerated by the elderly study participants, over the eight-week clinical study. We observed a positive effect on the participants weight, serum albumin, prealbumin, vitamin D and HDL-cholesterol. PMID- 25130630 TI - [Celiac disease in adult patients with type 1 diabetes mellitus]. AB - OBJECTIVE: To assess the prevalence of celiac disease in adult patients with type 1 diabetes mellitus (T1DM). Influence the new started treatment of celiac disease on glycemic control and body mass index (BMI) of the patients. Prevail the anti transglutaminase antibody (atTG) positivity one year after commencement of the therapy. METHODS: A retrospective assessment of celiac disease targeted screening in 465 adult T1DM patients at Diabetes Center, 1st Medical Department, University Hospital in Pilsen (80 % of all T1DM patients) from 1. 1. 2007 until 1. 7. 2011. Enterobiopsy was indicated in case of atTG-A (or atTG-G) positivity. In patients with newly started gluten-free diet, HbA1c and BMI within a year after diagnosis of celiac disease were compared to a year period six months after treatment commencement (3-4 visits), atTG was evaluated one year after treatment beginning. Paired T-test was used for statistical evaluation. RESULTS: The prevalence of all forms of celiac disease in the studied group was 10.5 %. Celiac disease diagnosed in childhood was found in 1.1 % patients (5/465). Positivity of atTG was newly observed in 9.5 % (44/465) patients. Three patients with atTG > 300 kIU/l refused the enterobiopsy examination. Celiac disease is highly plausible. The influence of gluten-free diet on BMI and HbA1c could not be evaluated due to the lack of compliance. 22 patients had a potential form of celiac disease (negative histology). Positive enterobiopsy was found in 19 patients (4.1 %). Another 3 patients had to be excluded from the subgroup of 22 patients (newly indicated gluten-free diet) as the HbA1c values and BMI were affected by the primary diagnosis of T1DM. Subgroup characteristics: 9 women and 7 men, mean age 38 +/- 12 years, diabetes duration 21 +/- 13 years, celiac disease diagnosed 20.7 +/- 13 years since first diagnosis of T1DM. No statistically significant change in HbA1c (67 +/- 11.4 vs 69 +/- 13.9 mmol/mol) was observed in the studied period, however and a significant change of BMI from 25.4 +/- 4.2 to 25.9 +/- 4.3 (p < 0.01) was found. The atTG positivity prevailed in 47 % (9/19) of patients after one year. CONCLUSION: A total prevalence of the celiac disease in the group of adult T1DM patients was 10.5 %. No significant change in HbA1c occurred following treatment, a significant change of BMI was observed. The atTG positivity prevailed in 47 % of patients after one year. PMID- 25130632 TI - [Genetics and pharmacogenetics of osteoporosis]. AB - Osteoporosis is a serious disease characterized by high morbidity and mortality due to atraumatic fractures. In pathogenesis of osteoporosis, except environment, internal factors, such as hormonal dysbalance and genetic background, are also in play. In this review, candidate genes for osteoporosis are classified according to metabolic or hormonal pathways, which regulate bone mineral density/and or quality (estrogen, RANKL/RANK/OPG, mevalonate, Wnt circuit, genes for collagen and vitamin D). Authors discuss the perspectives of practical utilization of pharmacogenetics (identification of single candidate genes using PCR) or pharmacogenomics (using genome wide association studies) in choice of optimal treatment of osteoporosis. Potentional predictors of effectivity of antiresorption therapy are genes ER, FDPS, Cyp19A1, VDR, Col1A1 and gene of Wnt pathway. Moreover, polymorphisms of CYP2C gene, but also FDPS may identify patients with high risk of undesirable effects of bisphosphonates (osteonecrosis of jaw). Unfortunately, results of the most association studies has not been confirmed by other investigators. The controversial results could be explained by different methodic approaches in individual studies (different sample size, homogenity of investigated groups, ethnic differences or linkage disquilibrium between genes). Key cliff of association studies is low variability (7-10 %) of bone phenotypes associated with investigated genes. Nevertheless, identification of new genes and verification their association with bone density and/or quality using both PCR and genome wide association studies remain to be a great challenge targeting optimal prevention and treatment of osteoporosis. PMID- 25130631 TI - [Acute pancreatitis - validation of revised Atlanta classification on 159 patients and prognostic factors]. AB - INTRODUCTION: In the last few years the Atlanta classification of acute pancreatitis (AP) have been revised. However prognostic markers of AP are still being searched for. The aim of this study is to validate the 3 severity categories proposed by the revised Atlanta classification. We also tried to reevaluate the association between two laboratory markers (leucocyte count and RDW - red cell distribution width) on admission and prognosis of the patients with AP. METHODS: 159 patients were included into the study. The patients were classified according to revised Atlanta criteria and the subgroups evaluated according to mortality, length of hospital stay and need for interventions. Leucocyte count and RDW on admission was evaluated in the patients. RESULTS: All the subgroups of patients were associated with significantly relevant differences in mortality, length of hospital stay and need for operations on pancreas. Leucocyte count and RDW were identified as significant predictors for severe AP and RDW was also identified as significant predictor for mortality in patients with AP. CONCLUSION: New categories of severity as defined by Revised Atlanta classification are describing well the mortality, length of hospital stay and need for interventions in the patients with AP. Leucocyte count and RDW on admission are needed to be confirmed as potential prognostic markers of severity and mortality in AP. PMID- 25130633 TI - [Importance of lymphangiogenesis and ultrastructure of lymphatic capillaries in metastasis of malignant melanoma]. AB - Lymphangiogenesis - proliferation of lymphatic capillaries - in melanoma and in its vicinity plays an important role in metastatic process of malign melanoma cells in organism. Melanoma produces epidermal growth factor EGF which induces vascular endothelial growth factor VEGF-C and thereby starts lymphangiogenesis. It is very probable that malignant melanoma cells enter lymphatic capillaries also through specialized inter-endothelial junctions (endothelial microvalves, primary valves) situated in their walls. After entry of malign cells into lymphatic capillaries, these cells travel in lymph to the sentinel lymph node. Malign cells metastasize through lymphatic vessels probably also directly into distal regional lymphatic nodes. Metastasizing through blood vessels is suggestible also in early stage melanoma. PMID- 25130634 TI - [What is new in heart failure with preserved ejection fraction within last five years?]. AB - Heart failure with preserved ejection fraction of left ventricle (heart failure with normal ejection fraction, HFPEF, HFNEF) is frequent disease with serious consequences. Incidence of HFPEF in population is still growing. The exact pathophysiological mechanism of HFPEF remain unclear .Recent evidence suggests a relationship between inflammation associated with obesity or Diabetes mellitus and progression of HFPEF. Consistently, it has been reported that serum concentration of some pro-inflammatory markers such as adiponectin is positively related to HFPEF. By HFPEF is attended diastolic dysfunction. Diastolic dysfunction is linked to many other cardiac and non-cardiac diseases. Despite the great effort and new therapeutic approaches the prognosis of HFPEF does not improve. The gold standard in HFPEF diagnosis remains heart catheterization. Electrocardiography, chest X-ray, blood examination including diagnostic markers of heart failure and mainly echocardiography with Doppler imaging are used diagnose the underlying disease leading to heart failure. PMID- 25130636 TI - [Osteoporosis and bone alterations in celiac disease in adults]. AB - Both celiac disease and osteoporosis are common diseases which are considered an emerging problem in medicine. Celiac disease is a condition at high risk for secondary osteoporosis. Osteoporosis or osteopenia are typically present in untreated adult symptomatic celiac disease with an overt malabsorption syndrome, but is found in about 50 % in suboptimally treated celiac patients, subclinical patients and asymptomatic adult celiac patients, too. Etiology of pathologic bone alteration in celiac disease is multifactorial; however, two main mechanisms are involved: intestinal malabsorption and chronic inflammation. The evaluation of bone mineral metabolism (total calcium/albumin, 25-OH vitamin D3 and parathormone levels in serum) and bone mineral density (densitometry) is recommended in the clinical management of celiac patients. Many studies have demonstrated that bone mineral density values in adults show a good improvement in the first period after the institution of gluten-free diet, the improvement is then unsatisfactory and treatment with a mineral-active drug should probably be considered. PMID- 25130637 TI - [Education model at the Clinic of Internal Medicine of the Faculty Hospital Motol Prague - our experience with local education project for young physicians on postgraduate education]. AB - In 2004 the principal legislative changes were accepted in the field of postgraduate medical education in Czech Republic (law No. 95/2004 Code). Replacement of two-stage system of specialized education by its one- stage option has brought some problems and according to our opinion did not lead to clear improvement of postgraduate education, more likely the other way around. Our effort to improve the quality of process of postgraduate specialization in internal medicine brought us to creation of own local system of postgraduate education using the next 4 basic principles: principle of robust internal base as a platform for the following specialization, principle of repeating to fix the knowledge, principle of knowledge control and last but not least principle of active participation in educational system. PMID- 25130635 TI - [Specifics of diabetes mellitus in women]. AB - Approximately 4 % of female population suffers from diabetes. A permanent interaction between diabetes, its treatment and sex hormonal changes (childhood, puberty, reproduction, pregnancy, menopause) occurs in those women. This review article summarizes up to date published studies concerning reciprocal relationship between diabetes and sexual development in women. PMID- 25130638 TI - [Zdenek Maratka and his share in the founding of the Czech Gastroenterological Society and its journal. Gastroenterological Society in Czech and Slovac republics]. AB - Zdenek Maratka (1914-2010) was a leading person in a Czech and Slovak gastroenterology in spite of the infavourable approach of the official communist policy to him.. He was one of the founders of gastroenterology in Czechoslovakia. He had been habilitated in 1948 for thesis Ulcerative colitis. Maratka stood at the first steps of foundation of Czech Gastroenterology Society very soon after the WW2 and followed with the preparation as a secretary ge-neral of the 8th ASNEMGE Congress in Prague 1968 and as a president the 1st Congress of Endoscopy in the very optimistic atmosphere of ,,Prague Spring". He was nominated or elected by several international gastroenterology organisations, during 1976-1980 had been President of ESGE. He started with editoring of Czech gastroenterology Association journal as a member of editorial board and had been its main editor between 1969-1999. His well appreciated novelty in the magazine was a short remarks in one or two sentences from the world scientific literature which appeared in every copy. As an editor emeritus he supported the quality of the journal by many advices and contributions including articles. PMID- 25130639 TI - [Crohn's disease surgery]. AB - Surgery of Crohns disease is an important part of the general treatment algorithm. The role of surgery is changing with the development of conservative procedures. The recent years have seen the return to early treatment of patients with Crohns disease. Given the character of the disease and its intestinal symptoms, a specific approach to these patients is necessary, especially regarding the correct choice of surgery. The paper focuses on the luminal damage of the small and large intestine including complications of the disease. We describe the individual indications for a surgical solution, including the choice of anastomosis or multiple / repeated surgeries. PMID- 25130640 TI - [Advances in diagnosis and therapy of inflammatory bowel diseases]. AB - The inflammatory bowel diseases have been an interesting topic not only for gastroenterologists, but also for other medical professionals, since the beginning of the last century, when this group of inflammatory autoimmune diseases was revealed. Logically, the doyen of Czech gastroenterology, Professor MUDr. Zdenek Maratka, DrSc., who dedicated a substantial part of his life to research into inflammatory bowel disease, particularly ulcerative colitis, was no exception. The current century is characterized by a very rapid development of scientific research and almost immediate introduction of scientific knowledge into clinical practice. In the area of inflammatory bowel diseases, the biggest advances have been made in diagnosis and therapy. The examination of the small bowel and large bowel by magnetic resonance belongs at the very pinnacle in the non-invasive diagnosis of the lower part of the gastrointestinal tract. The administration of biological therapy to patients with the most severe forms of inflammatory bowel diseases should be considered a breakthrough since the introduction of corticosteroids into the therapy of inflammatory bowel diseases in the 1950s. PMID- 25130641 TI - [Biological therapy in women with inflammatory bowel disease during pregnancy]. AB - The aim of this article is to objective review available research data regarding the safety of biological therapies during pregnancy and breastfeeding in women with inflammatory bowel disease. Biological therapies appear to be safe in pregnancy, as no increased risk of malformations has been demonstrated. Available clinical results suggest that the efficacy of infliximab and adalimumab in achieving clinical response and maintaining remission in pregnant patients might outweigh the theoretical risks of drug exposure to the fetus. If possible, anti TNF therapy should be stopped by the end of the second trimester due to transplacental transfer and potential risk for the fetus. The use of infliximab and adalimumab is probably compatible with breastfeeding. PMID- 25130642 TI - [Crohn's disease - etiopathogenetic factors]. AB - Crohn's disease is often purely inflammatory, but most patients develop complicated disease with strictures or fistulae. Specific etiopathogenesis of this severe disease is not definitely clear despite research efforts and learning of many pathogenetic mechanisms. Many studies have suggested that NOD2 mutations are associated with increased risk of complicated disease. Presence of NOD2 mutation itself is just one of factors contributing to development of this disease. Genetically predisposed individuals in combination with influence of environmental factors result in a disturbed innate (i.e., disturbed intestinal barrier, Paneth cell dysfunction) and adaptive (i.e., imbalance of effector and regulatory T cells and cytokines, migration and retention of leukocytes) immune response towards a diminished diversity of commensal microbiota. Data of meta analysis made so far provide ambiguous evidence to support top-down therapy based solely on single NOD2 mutations, but suggest that targeted early-intensive therapy for high-risk patients with two NOD2 mutations might be beneficial, but more prospective trials could answer these questions. PMID- 25130643 TI - [Etiology and pathogenesis of inflammatory bowel diseases]. AB - Zdenek Maratka has been the first physician, who had brought a new information for the Czech medical community with topic of inflammatory bowel diseases, which had been systematic studied for him. He had prepared an original theory - two component hypothesis about origin of ulcerative colitis, which had been developed and innovated by him for long time. From the international point of view, Maratka has had an extraordinary impact and significant contribution for recognition of ulcerative colitis and Crohn's disease. Despite the fact that the true origin of ulcerative colitis and Crohn's disease (UC) still remain elusive, basic as well as clinical research bring many new data on etiology and pathogenesis of this inflammatory condition. It seems clear that IBD originate from interaction of several intrinsic and extrinsic factors that contribute individually in a particular patient. Among internal factors the genes play an important role, because its influence on the mucosal immunity system and immunological response. Among the external factors importance are recognized the gut microbiota content, cigarette smoking and psychological stress. PMID- 25130644 TI - [History of surgical treatment of non-specific inflammatory bowel diseases]. AB - Treatment of non-specific inflammatory bowel diseases was from the start accompanied by forced operations. In the 19th and early 20th century operations were burdened with high mortality, but most were more successful than the limited possibilities of conservative treatment. Gradually developed principles for the treatment of Crohns disease, a length of bowel sparing surgery are still valid today. Surgical treatment of ulcerative colitis passed the time of colonic irrigation, bypass surgery, limited resection to todays gold standard - proctocolectomy with ileo-pouch-anal anastomosis. PMID- 25130645 TI - [Epidemiology of dyspepsia]. AB - Epidemiology of uninvestigated dyspepsia was studied in the Czech Republic for the first time in 2001. The aim of our current multi-centre prospective study was to evaluate dyspepsia using the same methods in a representative sample of general unselected population from the same geographical areas 10 years later. A total of 22 centres entered the study. A total of 1,836 subjects (aged 5-98 years) were enrolled. The overall prevalence of dyspepsia was 12 %; namely 3.5 % in subjects aged 5-24 years, 18 % among 25-64-year-old persons and 15 % in subjects 65 years. Despite the substantial decrease of Helicobacter pylori infection in the Czech Republic over the past 10 years, the prevalence and basic socio-demographic determinants of uninvestigated dyspepsia did not change significantly. PMID- 25130646 TI - [Management of patients with dyspepsia]. AB - Dyspepsia is a common clinical problem with an extensive differential diagnosis and a heterogeneous pathophysiology. Dyspepsia affects up to 40 % of the general population and significantly reduces quality of life. According to the Rome III criteria, dyspepsia is defined as one or more of the following symptoms: epigastric pain and/or burning (classified as epigastric pain syndrome), postprandial fullness and/or early satiation (classified as postprandial distress syndrome). Initial evaluation should focus on the identification and treatment of potential causes of symptoms such as gastroesophageal reflux disease, peptic ulcer disease, and medication side effects but also on recognizing those at risk for more serious conditions such as gastric cancer. An empiric PPI trial or "test and treat" strategy for Helicobacter pylori are the initial approaches to a patient with dyspepsia, followed by endoscopy if initial management fails. Once an organic cause for symptoms is excluded, a diagnosis of functional dyspepsia is made. This article will review the definition, etiology, and general approach to the evaluation and management of the patient with dyspepsia including the role of proton-pump inhibitors, treatment of Helicobacter pylori, and endoscopy. PMID- 25130647 TI - [Endoscopic classification of colon and rectal neoplasias]. AB - Along with the dynamic evolution of the new field of digestive endoscopy, the need of unified and unambiguous terms for endoscopic findings arose in the second half of the 20th century. In collaboration with the OMED members, professor Zdenek Maratka drew up the first internationally acknowledged terminology for digestive endoscopy which was used in the full range for a period of almost 20 years. The technical progress later brought with it endoscopes which made it possible to view flat lesions, frequently overlooked until then. The classification of the surface lesions was further specified by the Paris Classification which drew from the experience of Japanese endoscopists. Thanks to the new endoscopic methods of imaging mucosa in vivo and the pit-pattern and vascular-pattern classification, we can currently estimate the biological nature of lesion with great accuracy and therefore choose the best therapeutic procedure. PMID- 25130649 TI - Efficacy of low-dose human chorionic gonadotropin therapy in dogs with spermatogenic dysfunction: a preliminary study. AB - Human chorionic gonadotropin (hCG) is a glycoprotein used in the treatment of spermatogenic dysfunction. However, previous studies performed in dogs show that repeated administration of large doses of hCG produces antibodies against hCG. In this study, we examined the efficacy of low-dose injections of hCG in four male dogs with spermatogenic dysfunction and low plasma testosterone (T) levels. We administered 100 IU hCG per animal, five times at 3-day intervals, and evaluated the changes in semen quality and plasma T levels. The total number of sperm in ejaculate, the percentage of progressively motile sperm and the plasma T levels had increased by 3-5 weeks after the first injection of hCG in three of the four dogs, but were unchanged in the fourth dog. These findings indicate that temporary improvement of the semen quality of dogs with spermatogenic dysfunction and low plasma T levels is possible after five low-dose injections of hCG. PMID- 25130648 TI - Engineering persister-specific antibiotics with synergistic antimicrobial functions. AB - Most antibiotics target growth processes and are ineffective against persister bacterial cells, which tolerate antibiotics due to their reduced metabolic activity. These persisters act as a genetic reservoir for resistant mutants and constitute a root cause of antibiotic resistance, a worldwide problem in human health. We re-engineer antibiotics specifically for persisters using tobramycin, an aminoglycoside antibiotic that targets bacterial ribosomes but is ineffective against persisters with low metabolic and cellular transport activity. By giving tobramycin the ability to induce nanoscopic negative Gaussian membrane curvature via addition of 12 amino acids, we transform tobramycin itself into a transporter sequence. The resulting molecule spontaneously permeates membranes, retains the high antibiotic activity of aminoglycosides, kills E. coli and S. aureus persisters 4-6 logs better than tobramycin, but remains noncytotoxic to eukaryotes. These results suggest a promising paradigm to renovate traditional antibiotics. PMID- 25130650 TI - Long-term therapeutic and reporter gene expression in lentiviral vector treated cystic fibrosis mice. AB - BACKGROUND: Persistent reporter gene and cystic fibrosis transmembrane conductance regulator (CFTR) nasal airway gene expression can be achieved with a single lentiviral (LV) gene vector dosing when coupled with a preparatory lysophosphatidylcholine (LPC) airway pre-treatment. In the present study, we characterised the duration of gene expression in individual cystic fibrosis (CF) knockout mice (cftr(tm1unc)) over their lifetimes. METHODS: CF mouse nasal airways were treated with LV-Rx, a mixture of a therapeutic LV-CFTR gene vector and a LV-luciferase reporter gene vector, after pre-treatment with LPC. Control groups received either PBS sham pre-treatment followed by LV-Rx, or LPC prior to delivery of a LV vector containing no transgene (LV-MT). Airway reporter gene expression was monitored by bioluminescence, and functional CFTR expression was assessed via nasal transepithelial potential difference measurements at regular intervals up to 21 months. The presence of the CFTR transgene in the nasal septa, liver and spleen tissues were assessed by a quantitative polymerase chain reaction. Circulating antibodies to the vector glycoprotein envelope and to the luciferase protein were also measured. RESULTS: The combined use of LPC and LV gene vectors in the nasal airway produced enhanced and sustained luciferase and CFTR gene expression lasting at least 12 months. Improved survival was also observed in CF knockout mice treated with the LV vector mixture compared to all control CF mouse groups. CONCLUSIONS: The present study showed that our airway pre-treatment and gene delivery technique resulted in sustained functional CFTR expression and improved survival in CF mice. PMID- 25130651 TI - Association between combative behavior requiring intervention and delirium in hospitalized patients. AB - BACKGROUND: We hypothesized that delirium contributes to combative behavior requiring intervention in hospitalized patients. Delirium identification would therefore potentially provide an opportunity for prevention and early identification of patients at risk, thereby improving safety for patients and staff. OBJECTIVE: To determine whether delirium is associated with combative behavior requiring intervention in a general hospital population. DESIGN: Case control study. SETTING: A 336-bed, nonuniversity, teaching hospital serving adults in the Pacific Northwest. PATIENTS: One hundred twenty consecutive hospitalized patients with combative behavior requiring intervention compared to 159 randomly selected inpatient control subjects, all from 2011. INTERVENTION: Bivariate statistics were used to compare demographics; diagnoses; presence of delirium, dementia, substance use, other psychiatric diagnosis; medications; hospital length of stay; and discharge disposition. We used stepwise logistic regression to determine the association of combative behavior requiring intervention with delirium after adjustment for covariates. RESULTS: Delirium preceding the combative behavior was present in 50% (60/120) of patients with combative behavior requiring intervention compared to 16% (26/159) of controls (P < 0.001). Combative-behavior patients were hospitalized longer (9.4 vs 4.5 days, P < 0.001), and were more likely to be discharged to a skilled nursing facility (26%, 31/120) or to leave against medical advice (10%, 12/120, P < 0.001). Delirium was strongly associated with combative behavior requiring intervention, after adjustment (odds ratio: 3.8, 95% confidence interval: 2.0-7.3, P < 0.001). CONCLUSION: Delirium is strongly associated with combative behavior requiring intervention, which poses a significant safety risk for patients and staff. PMID- 25130652 TI - Klotho suppresses renal tubulo-interstitial fibrosis by controlling basic fibroblast growth factor-2 signalling. AB - Increased basic fibroblast growth factor-2 (FGF2) and reduced Klotho have both been reported to be closely associated with renal fibrosis. However, the relationship between Klotho and FGF2 remains unclear. We demonstrate that FGF2 induced tubulo-epithelial plasticity in cultured HK-2 cells, accompanied by a reduction in Klotho expression, whereas recombinant Klotho protein could inhibit the action of FGF2. The FGF2 effects required extracellular signal-regulated protein kinase 1/2 activation, which was suppressed by Klotho. Moreover, Klotho also restrained FGF2-induced fibroblast proliferation and activation. The inhibitory effect of Klotho on the activity of FGF2 was likely due to its potent ability to compete with FGF2 binding to FGF receptor 1. Unilateral ureteral obstruction (UUO)-induced renal fibrosis was associated with an increase in FGF2 and a reduction in Klotho expression in wild-type mice, whereas FGF2(-/-) mice largely preserved Klotho expression and developed only mild renal fibrosis after obstructive injury. Furthermore, administration of Klotho protein in UUO mice significantly reduced renal fibrosis, concomitant with a marked suppression of FGF2 production and signalling. These studies demonstrate a feedback loop between Klotho depletion and FGF2 activation in renal fibrosis. Our results also suggest that Klotho treatment reduces renal fibrosis, at least in part, by inhibiting FGF2 signalling. PMID- 25130653 TI - Telocytes in liver regeneration: possible roles. AB - Telocytes (TCs) are a novel type of interstitial cells which are potentially involved in tissue regeneration and repair (www.telocytes.com). Previously, we documented the presence of TCs in liver. However, the possible roles of TCs in liver regeneration remain unknown. In this study, a murine model of partial hepatectomy (PH) was used to induce liver regeneration. The number of TCs detected by double labelling immunofluorescence methods (CD34/PDGFR-alpha, CD34/PDGFR-beta and CD34/Vimentin) was significantly increased when a high level of hepatic cell proliferation rate (almost doubled) as shown by 5-ethynyl-2' deoxyuridine (EdU) immunostaining and Western Blot of Proliferating cell nuclear antigen (PCNA) was found at 48 and 72 hrs post-PH. Meanwhile, the number of CK-19 positive-hepatic stem cells peaked at 72 hrs post-PH, co-ordinating with the same time-point, when the number of TCs was most significantly increased. Taken together, the results indicate a close relationship between TCs and the cells essentially involved in liver regeneration: hepatocytes and stem cells. It remains to be determined how TCs affect hepatocytes proliferation and/or hepatic stem cell differentiation in liver regeneration. Besides intercellular junctions, we may speculate a paracrine effect via ectovesicles. PMID- 25130654 TI - Slit2 is decreased after spontaneous labour in myometrium and regulates pro labour mediators. AB - Preterm birth, a global healthcare problem, is commonly associated with inflammation. As Slit2 plays an emerging role in inflammation, the purpose of this study was to determine the effect of Slit2 on labour mediators in human gestational tissues. Slit2 mRNA and protein expression were assessed using qRT PCR and immunohistochemistry in foetal membranes and myometrium obtained before and after labour. Slit2 silencing was achieved using siRNA in primary myometrial cells. Pro-inflammatory and pro-labour mediators were evaluated by qRT-PCR, ELISA and gelatin zymography. Slit2 mRNA and protein expression were found to be significantly lower in myometrium after labour onset. There was no effect of term or preterm labour on Slit2 expression in foetal membranes. Slit2 mRNA expression was decreased in myometrium treated with LPS and IL-1beta. Slit2 siRNA in myometrial cells increased IL-1beta-induced pro-inflammatory cytokine gene expression and release (IL-6 and IL-8), COX-2 expression and prostaglandin PGE2 and PGF2alpha release, and MMP-9 gene expression and pro MMP-9 release. There was no effect of Slit2 siRNA on IL-1beta-induced NF-kappaB transcriptional activity. Our results demonstrate that Slit2 is decreased in human myometrium after labour and our knock-down studies describe an anti-inflammatory effect of Slit2 in myometrial cells. PMID- 25130655 TI - Pollination ecology and inbreeding depression control individual flowering phenologies and mixed mating. AB - We analyze evolution of individual flowering phenologies by combining an ecological model of pollinator behavior with a genetic model of inbreeding depression for plant viability. The flowering phenology of a plant genotype determines its expected daily floral display which, together with pollinator behavior, governs the population rate of geitonogamous selfing (fertilization among flowers on the same plant). Pollinators select plant phenologies in two ways: they are more likely to visit plants displaying more flowers per day, and they influence geitonogamous selfing and consequent inbreeding depression via their abundance, foraging behavior, and pollen carry-over among flowers on a plant. Our model predicts two types of equilibria at stable intermediate selfing rates for a wide range of pollinator behaviors and pollen transfer parameters. Edge equilibria occur at maximal or minimal selfing rates and are constrained by pollinators. Internal equilibria occur between edge equilibria and are determined by a trade-off between pollinator attraction to large floral displays and avoidance of inbreeding depression due to selfing. We conclude that unavoidable geitonogamous selfing generated by pollinator behavior can contribute to the common occurrence of stable mixed mating in plants. PMID- 25130656 TI - A presenilin 1 mutation in the first case of Alzheimer's disease: revisited. AB - BACKGROUND: Recently, a single point mutation in the presenilin 1 (PSEN1) gene of the first described Alzheimer's disease (AD) patient Auguste D was reported by Muller and co-workers. However, the sequencing results of the DNA from a 100-year old tissue contained some uncertainties. METHODS: We heat extracted DNA from an original histological slice of Auguste D's brain and used nested polymerase chain reaction for the amplification of different exons of genes known to be affected in familial forms of AD. RESULTS: Our sequencing analysis did not validate the reported mutation. Furthermore, an extended sequencing analysis of Auguste D's DNA revealed no indication of a nonsynonymous hetero- or homozygous mutation in the exons of APP, PSEN1, and PSEN2 genes comprising the already known familial AD mutations. CONCLUSION: Despite the wealth of data from Muller and co-workers, our results emphasize the requirement of more detailed analysis of Auguste D's DNA in future. PMID- 25130657 TI - Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. AB - BACKGROUND: Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD. METHODS: Blood exosomes obtained at one time-point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two time-points from others (n = 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD pathogenic exosomal proteins were extracted and quantified by enzyme-linked immunosorbent assays. RESULTS: Mean exosomal levels of total tau, P-T181-tau, P S396-tau, and amyloid beta 1-42 (Abeta1-42) for AD and levels of P-T181-tau and Abeta1-42 for FTD were significantly higher than for case-controls. Step-wise discriminant modeling incorporated P-T181-tau, P-S396-tau, and Abeta1-42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P T181-tau, and Abeta1-42 were significantly higher than for controls both 1 to 10 years before and when diagnosed with AD. CONCLUSIONS: Levels of P-S396-tau, P T181-tau, and Abeta1-42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset. PMID- 25130659 TI - Survival and early recourse to care for dementia: A population based study. AB - BACKGROUND: A large proportion of dementia cases are still undiagnosed. Although early dementia care has been hypothesized to benefit both patients and families, evidence-based benefits are lacking. Thus, investigating the benefits for newly demented persons according to their recourse to care in the "real life" appears critical. METHODS: We examined the relation between initial care recourse care and demented individuals' survival in a large cohort of incident dementia cases screened in a prospective population-based cohort, the Three-City Study. We assessed recourse to care for cognitive complaint at the early beginning of dementia when incident cases were screened. We classified patients in three categories: no care recourse, general practitioner consultation or specialist consultation. We used proportional hazard regression models to test the association between recourse to care and mortality, adjusting on socio demographical and clinical characteristics. RESULTS: Two hundred and fifty-three incident dementia participants were screened at the 2 year or 4 year follow-up. One third of the incident demented individuals had not consulted a physician for cognitive problems. Eighty-six (34.0%) individuals had reported a cognitive problem only to their general practitioner (GP) and 80 (31.6%) had consulted a specialist. Mean duration of follow-up after incident dementia was 5.1 years, during which 146 participants died. After adjustment on potential confounders, participants who had consulted a specialist early in the disease course presented a poorer survival than those who did not consult any physician (hazard ratio = 1.64, 95% confidence interval 1.03-2.62). There was a trend but no significant differential survival profile between participants who complained to their GP and those without any care recourse. CONCLUSION: Neither recourse to a specialist nor recourse to GP improve survival of new dementia cases. Those who had consulted a specialist early in the disease course even reported a worse life expectancy than those who did not. PMID- 25130658 TI - Delphi definition of the EADC-ADNI Harmonized Protocol for hippocampal segmentation on magnetic resonance. AB - BACKGROUND: This study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures, to define standard operating procedures for magnetic resonance (MR) based manual hippocampal segmentation. METHODS: The panel received a questionnaire regarding whole hippocampus boundaries and segmentation procedures. Quantitative information was supplied to allow evidence-based answers. A recursive and anonymous Delphi procedure was used to achieve convergence. Significance of agreement among panelists was assessed by exact probability on Fisher's and binomial tests. RESULTS: Agreement was significant on the inclusion of alveus/fimbria (P = .021), whole hippocampal tail (P = .013), medial border of the body according to visible morphology (P = .0006), and on this combined set of features (P = .001). This definition captures 100% of hippocampal tissue, 100% of Alzheimer's disease-related atrophy, and demonstrated good reliability on preliminary intrarater (0.98) and inter-rater (0.94) estimates. DISCUSSION: Consensus was achieved among international experts with respect to hippocampal segmentation using MR resulting in a harmonized segmentation protocol. PMID- 25130660 TI - Diagnostic value of dilated intercellular space and histopathologic scores in gastroesophageal reflux disease. AB - The aim of this paper is to investigate the diagnostic value of histopathologic score and the dilated intercellular space (DIS) in patients with gastroesophageal reflux disease (GERD) and functional heartburn (FH). Participants with GERD symptoms including reflux esophagitis, non-erosive reflux disease (NERD), Barrett's esophagus (BE), functional heartburn (FH), along with a control group with atypical GERD-like symptom (Sym-C), and asymptomatic healthy volunteers (H C) were administered GERD questionnaire, and subjected to endoscopy and biopsies, as well as 24-hour pH-impedance monitoring. Biopsies were evaluated using standards from the 2011 Esohisto Project after Hematoxylin-Eosin staining. DIS was measured quantitatively under light microscopy. Among the total of 565 participants with qualified biopsy specimens, the mean DIS of the reflux esophagitis (RE) group was significantly wider compared with the other five groups. DIS in patients with GERD-like symptoms was significantly wider compared with the H-C. No significant differences were observed between NERD and FH. Results from 24-hour pH-impedance monitoring indicated that only the DIS of patients with acid reflux or the amount of acid reflux episodes in patients with DIS was significantly wider compared with patients with nonacid reflux or patients without DIS (P < 0.001). With DIS = 0.9 MUm as the cutoff value, the sensitivity and specificity were 62.6% and 54.1%, respectively. Using the total histopathologic score > 3 as the diagnostic criterion, the sensitivity and specificity were 71.7% and 47.4%. DIS is closely associated with GERD and acid reflux. The diagnostic value of histological scores in lower esophagus in GERD is very similar to that of the quantitative measurement of DIS. PMID- 25130662 TI - SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal damage and cognitive deficits in a rat model of Alzheimer's disease induced by amyloid beta and excitatory amino acids. AB - Basic fibroblast growth factor (bFGF/FGF-2) is known to possess neuroprotective and neurite outgrowth activity properties. In this study, the effects of a novel synthetic compound that mimics the neuroprotective properties of bFGF - SUN11602 were examined in vitro and in vivo. SUN11602 promoted neurite outgrowth of primarily cultured rat hippocampal neurons. For the in vivo study, an Alzheimer's disease (AD) model with severe damage to the hippocampal tissue was constructed by injecting the hippocampi of rats with aggregated Abeta1-40, followed 48 h later by an injection of ibotenate [an agonist for N-methyl-d-aspartate (NMDA) receptor]. Oral administration of SUN11602 at the midpoint of Abeta1-40 and ibotenate injections attenuated short-term memory impairment in the Y-maze test, as well as spatial learning deficits in the water maze task. In addition, the SUN11602 treatment inhibited the increase of peripheral-type benzodiazepine binding sites (PTBBS), which are a marker for gliosis. A negative correlation was found between PTBBS numbers and learning capacity in the water maze task. These results suggest that SUN111602 improved memory and learning deficits in the hippocampally lesioned rats by preventing neuronal death and/or promotion of neurite outgrowth. Taken together, these results indicate that SUN11602, a bFGF like compound with neuroprotective and neurite outgrowth activity, may be beneficial for the treatment of progressive neurodegenerative diseases such as AD. PMID- 25130663 TI - A new Drosophila model to study the interaction between genetic and environmental factors in Parkinson's disease. AB - The fruit fly Drosophila melanogaster has long been used as a model organism for human diseases, including Parkinson's disease (PD). Its short lifespan, simple maintenance, and the widespread availability of genetic tools allow researchers to study disease mechanisms as well as potential drug therapies. Many different PD models have already been developed, including ones utilizing mutated alpha-Syn and chronic exposure to rotenone. However, few animal models have been used to study interaction between the PD causing factors. In this study, we developed a new model of PD for use in the larval stage in order to study interaction between genetic and environmental factors. First, the 3rd instar larvae (90-94 hours after egg laying) expressing a mutated form of human alpha-Syn (A53T) in dopaminergic (DA) neurons were video-taped and quantified for locomotion (e.g. crawling pattern and speed) using ImageJ software. A53T mutant larvae showed locomotion deficits and also loss of DA neurons in age-dependent manner. Similarly, larvae chronically exposed to rotenone (10 MUM in food) showed age dependent decline in locomotion accompanied by loss of DA neurons. We further show that combining the two models, by exposing A53T mutant larvae to rotenone, causes a much more severe PD phenotype (i.e. locomotor deficit). Our finding shows interaction between genetic and environmental factors underlying development of PD symptoms. This model can be used to further study mechanisms underlying the interaction between genes and different environmental PD factors, as well as to explore potential therapies for PD treatment. PMID- 25130665 TI - Internal and external spatial attention examined with lateralized EEG power spectra. AB - Several authors argued that retrieval of an item from visual short term memory (internal spatial attention) and focusing attention on an externally presented item (external spatial attention) are similar. Part of the neuroimaging support for this view may be due to the employed experimental procedures. Furthermore, as internal spatial attention may have a more induced than evoked nature some effects may not have been visible in event related analyses of the electroencephalogram (EEG), which limits the possibility to demonstrate differences. In the current study, a colored frame cued which stimulus, one out of four presented in separate quadrants, required a response, which depended on the form of the cued stimulus (circle or square). Importantly, the frame occurred either before (precue), simultaneously with (simultaneous cue), or after the stimuli (postcue). The precue and simultaneous cue condition both concern external attention, while the postcue condition implies the involvement of internal spatial attention. Event-related lateralizations (ERLs), reflecting evoked effects, and lateralized power spectra (LPS), reflecting both evoked and induced effects, were determined. ERLs revealed a posterior contralateral negativity (PCN) only in the precue condition. LPS analyses on the raw EEG showed early increased contralateral theta power at posterior sites and later increased ipsilateral alpha power at occipito-temporal sites in all cue conditions. Responses were faster when the internally or externally attended location corresponded with the required response side than when not. These findings provide further support for the view that internal and external spatial attention share their underlying mechanism. PMID- 25130661 TI - The protective role of prosaposin and its receptors in the nervous system. AB - Prosaposin (also known as SGP-1) is an intriguing multifunctional protein that plays roles both intracellularly, as a regulator of lysosomal enzyme function, and extracellularly, as a secreted factor with neuroprotective and glioprotective effects. Following secretion, prosaposin can undergo endocytosis via an interaction with the low-density lipoprotein-related receptor 1 (LRP1). The ability of secreted prosaposin to promote protective effects in the nervous system is known to involve activation of G proteins, and the orphan G protein coupled receptors GPR37 and GPR37L1 have recently been shown to mediate signaling induced by both prosaposin and a fragment of prosaposin known as prosaptide. In this review, we describe recent advances in our understanding of prosaposin, its receptors and their importance in the nervous system. PMID- 25130666 TI - Role of Re species and acid cocatalyst on Ir-ReOx /SiO2 in the C-O hydrogenolysis of biomass-derived substrates. AB - The catalytic performance of ReOx -modified Ir metal catalyst in the hydrogenolysis of C-O bonds is strongly dependent on the choice of solvent. The acidic property of the Re species becomes obvious in the alkane solvent, and the hydrogenolysis reaction proceeds mainly by acid-catalyzed dehydration and the subsequent metal-catalyzed hydrogenation. The acidic property of the Re species is weakened in water; however, the hydrogenolysis reaction proceeds in water via a direct mechanism involving SN 2-like attack of a hydride species at the interface between Ir and ReOx on the adsorbed Re alkoxide species. This mechanism enabled the selective dissociation of the C-O bond neighboring the CH2 OH group. PMID- 25130664 TI - Kisspeptin-10 potentiates miniature excitatory postsynaptic currents in the rat supraoptic nucleus. AB - Kisspeptin is the natural ligand of the G protein-coupled receptor -54 and plays a major role in gonadotropin-releasing hormone secretion in the hypothalamus. Kisspeptin-10 is an endogenous derivative of kisspeptin and has 10 -amino acids. Previous studies have demonstrated that central administration of kisspeptin-10 stimulates the secretion of arginine vasopressin (AVP) in male rats. We examined the effects of kisspeptin-10 on- excitatory synaptic inputs to magnocellular neurosecretory cells (MNCs) including AVP neurons in the supraoptic nucleus (SON) by obtaining in vitro whole-cell patch-clamp recordings from slice preparations of the rat brain. The application of kisspeptin-10 (100 nM-1 MUM) significantly increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in a dose-related manner without affecting the amplitude. The kisspeptin-10-induced potentiation of the mEPSCs was significantly attenuated by previous exposure to the kisspeptin receptor antagonist kisspeptin-234 (100 nM) and to the protein kinase C inhibitor bisindolylmaleimide I (20 nM). These results suggest that kisspeptin-10 participates in the regulation of synaptic inputs to the MNCs in the SON by interacting with the kisspeptin receptor. PMID- 25130668 TI - Association between right ventricular dysfunction and restrictive lung disease in childhood cancer survivors as measured by quantitative echocardiography. AB - BACKGROUND: Restrictive lung disease is a complication in childhood cancer survivors who received lung-toxic chemotherapy and/or thoracic radiation. Left ventricular dysfunction is documented in these survivors, but less is known about right ventricular (RV) function. Quantitative echocardiography may help detect subclinical RV dysfunction. The aim of this study was to assess RV function quantitatively in childhood cancer survivors after lung-toxic therapy. PROCEDURES: We identified records of 33 childhood cancer survivors who (1) were treated with lung-toxic therapy and/or radiation, (2) were cancer-free for >= one year after therapy, and (3) had pulmonary function tests and echocardiograms from their most recent follow-up visit. RESULTS: Participants' mean age was 11.6 +/- 4.5 years at cancer diagnosis and 23 +/- 8.6 years at evaluation. The most common diagnosis was lymphoma/leukemia (n = 27). Twenty-nine subjects had anthracycline exposure. Eleven of the 33 subjects demonstrated restrictive pulmonary impairment (total lung capacity 3.69 +/- 1.5 L [69.3 +/- 22.4% predicted]). Among quantitative measures of RV function, isovolumetric acceleration (IVA), a measure of contractility, was significantly lower in the group with restrictive lung disease (2.42 +/- 0.56 vs. 1.83 +/- 0.78 m/sec(2); P < 0.05). There was a trend towards lower tissue Doppler derived S' and tricuspid annular plane systolic excursion in the group with restrictive lung disease. Subjects with restrictive lung disease were found to have >= 2 abnormal parameters (P < 0.01). CONCLUSION: IVA may detect early RV dysfunction in childhood cancer survivors with restrictive lung disease. Our findings require confirmation in a larger study population and validation by cardiac MRI. PMID- 25130667 TI - D-Cycloserine ameliorates social alterations that result from prenatal exposure to valproic acid. AB - Prenatal exposure to valproic acid (VPA) alters rodent social interactions in a dose-dependent way: exposure to a high dose of VPA (>500 mg/kg) mid-gestation decreases social interactions whereas a moderate dose of VPA (350 mg/kg) increases peer-directed social behavior. The moderate dose also decreases expression of the mRNA for serine in amygdala and orbitofrontal cortex. In this study, we examined whether d-cycloserine could ameliorate VPA-induced alterations in ultrasonic vocalizations (USVs), social interactions, and locomotor activity. Pregnant Sprague Dawley rats were given intraperintoneal injections of VPA (200mg/kg each) on gestational days 12, 12.5 and 13; controls were injected with saline. Offspring received a subcutaneous injection of saline or d-cycloserine (32 or 64 mg/kg) either acutely (1h prior to testing) or repeatedly (once per day for four days). Social interactions were assessed during late adolescence, and USVs were recorded concomitantly. Male and female rats that were exposed to VPA demonstrated more locomotor activity than control animals during habituation to the testing chamber. VPA-exposed males showed increased play fighting. d Cycloserine normalized the VPA-induced increase in play fighting in males and also increased social motivation in females. When the pair contained a VPA exposed rat, significantly fewer USVs were emitted and 16% of the vocalizations were of a novel waveform. These effects were not seen in pairs containing VPA exposed animals that were treated with d-cycloserine. Overall, these findings are consistent with data from other laboratories suggesting that d-cycloserine may be a promising pharmacotherapeutic compound for improving social behavior disorders. PMID- 25130669 TI - Mechano-actuated ultrafast full-colour switching in layered photonic hydrogels. AB - Photonic crystals with tunability in the visible region are of great interest for controlling light diffraction. Mechanochromic photonic materials are periodically structured soft materials designed with a photonic stop-band that can be tuned by mechanical forces to reflect specific colours. Soft photonic materials with broad colour tunability and fast colour switching are invaluable for application. Here we report a novel mechano-actuated, soft photonic hydrogel that has an ultrafast response time, full-colour tunable range, high spatial resolution and can be actuated by a very small compressive stress. In addition, the material has excellent mechanical stability and the colour can be reversibly switched at high frequency more than 10,000 times without degradation. This material can be used in optical devices, such as full-colour display and sensors to visualize the time evolution of complicated stress/strain fields, for example, generated during the motion of biological cells. PMID- 25130670 TI - Molecular crystals by design? AB - In this Viewpoint, the impact of the paper published by Gautam R. Desiraju and Angelo Gavezzotti (J. Chem. Soc., Chem. Commun., 1989, 621) upon the development of Crystal Engineering, now recognised a key discipline in contemporary chemical/pharmaceutical/materials science, is discussed. PMID- 25130671 TI - Epidermal axonal swellings in painful and painless diabetic peripheral neuropathy. AB - INTRODUCTION: The pathophysiology of neuropathic pain (NeP) in diabetic peripheral neuropathy (DPN) is unclear. A potential pathological feature associated with intraepidermal nerve fiber density (IENFD) loss in DPN is axonal swellings. METHODS: We determined the prevalence of intraepidermal axonal swellings in DPN patients with or without NeP and compared the findings with diabetes patients without DPN, patients with idiopathic neuropathy with NeP, and control subjects. The primary outcome measure was the ratio of axonal swellings to IENFD. Secondary outcome measures included clinical neuropathy severity and assessment for messenger RNA for voltage-gated sodium and calcium channels. RESULTS: IENFD was depressed in DPN (with/without pain) and in idiopathic neuropathy patients. Axonal swelling ratios were similar for DPN subjects with and without pain. There was no overexpression of voltage-gated ion channels in epidermis from DPN patients. Clinical neuropathy severity was only related to IENFD. CONCLUSIONS: There was no clinical relationship to pain or clinical neuropathy severity for axonal swellings in DPN. PMID- 25130672 TI - A simplified method to estimate body growth parameters of the European eel Anguilla anguilla. AB - A simple approach is proposed to fit a body growth model for the European eel Anguilla anguilla to data-poor case studies. The model is a modified von Bertalanffy curve allowing for delayed sex determination and sexual dimorphism. The proposed procedure provides preliminary estimates of model parameters on the basis of average age and body length of silver eels. PMID- 25130673 TI - Liver allocation: can we ever get it right and should we ever get it right? PMID- 25130675 TI - Implementation of an emergency department sign-out checklist improves transfer of information at shift change. AB - BACKGROUND: Transitions of care are ubiquitous in the emergency department (ED) and inevitably introduce the opportunity for errors. Few emergency medicine residency programs provide formal training or a standard process for patient handoffs. Checklists have been shown to be effective quality-improvement measures in inpatient settings and may be a feasible method to improve ED handoffs. OBJECTIVE: To determine if the use of a sign-out checklist improves the accuracy and efficiency of resident sign-out in the ED. METHODS: A prospective pre /postinterventional study of residents rotating in the ED at a tertiary academic medical center. Trained research assistants observed resident sign-out during shift change over a 2-week period and completed a data collection tool to indicate whether or not key components of sign-out occurred and time to sign out each patient. An electronic sign-out checklist was implemented using a multi faceted educational effort. A 2-week postintervention observation phase was conducted. Proportions, means, and nonparametric comparison tests were calculated using STATA. RESULTS: One hundred fifteen sign-outs were observed prior to checklist implementation and 114 were observed after. Significant improvements were seen in four sign-out components: reporting of history of present illness increased from 81% to 99%, ED course increased from 75% to 86%, likely diagnosis increased from 60% to 77%, and team awareness of plan increased from 21% to 41%. Use of the repeat-back technique decreased from 13% to 5% after checklist implementation and time to sign-out showed no significant change. CONCLUSION: Implementation of a checklist improved the transfer of information without increasing time to sign-out. PMID- 25130674 TI - Degradation of toluene by ortho cleavage enzymes in Burkholderia fungorum FLU100. AB - Burkholderia fungorum FLU100 simultaneously oxidized any mixture of toluene, benzene and mono-halogen benzenes to (3-substituted) catechols with a selectivity of nearly 100%. Further metabolism occurred via enzymes of ortho cleavage pathways with complete mineralization. During the transformation of 3 methylcatechol, 4-carboxymethyl-2-methylbut-2-en-4-olide (2-methyl-2-enelactone, 2-ML) accumulated transiently, being further mineralized only after a lag phase of 2 h in case of cells pre-grown on benzene or mono-halogen benzenes. No lag phase, however, occurred after growth on toluene. Cultures inhibited by chloramphenicol after growth on benzene or mono-halogen benzenes were unable to metabolize 2-ML supplied externally, even after prolonged incubation. A control culture grown with toluene did not show any lag phase and used 2-ML as a substrate. This means that 2-ML is an intermediate of toluene degradation and converted by specific enzymes. The conversion of 4-methylcatechol as a very minor by-product of toluene degradation in strain FLU100 resulted in the accumulation of 4-carboxymethyl-4-methylbut-2-en-4-olide (4-methyl-2-enelactone, 4-ML) as a dead-end product, excluding its nature as a possible intermediate. Thus, 3 methylcyclohexa-3,5-diene-1,2-diol, 3-methylcatechol, 2-methyl muconate and 2-ML were identified as central intermediates of productive ortho cleavage pathways for toluene metabolism in B. fungorum FLU100. PMID- 25130676 TI - Genetic variability in anthocyanin composition and nutritional properties of blue, purple, and red bread (Triticum aestivum L.) and durum (Triticum turgidum L. ssp. turgidum convar. durum) wheats. AB - Renewed interest in breeding for high anthocyanins in wheat (Triticum ssp.) is due to their antioxidant potential. A collection of different pigmented wheats was used to investigate the stability of anthocyanins over three crop years. The data show higher anthocyanins in blue-aleurone bread wheat (Triticum aestivum L.), followed by purple- and red-pericarp durum wheat (Triticum turgidum L. ssp. turgidum convar. durum), using cyanidin 3-O-glucoside as standard. HPLC of the anthocyanin components shows five to eight major anthocyanins for blue wheat extracts, compared to three anthocyanins for purple and red wheats. Delphinidin 3 O-rutinoside, delphinidin 3-O-glucoside, and malvidin 3-O-glucoside are predominant in blue wheat, with cyanidin 3-O-glucoside, peonidin 3-O-galactoside, and malvidin 3-O-glucoside in purple wheat. Of the total anthocyanins, 40-70% remain to be structurally identified. The findings confirm the high heritability for anthocyanins, with small genotype * year effects, which will be useful for breeding purposes, to improve the antioxidant potential of cereal-based foods. PMID- 25130677 TI - Comparison of adenocarcinoma (ACA) and squamous cell carcinoma (SCC) of the uterine cervix in a sub-optimally screened cohort: a population-based epidemiologic study of 51,842 women in Brazil. AB - BACKGROUND: Most cancers of the uterine cervix are SCC, but the relative and absolute incidence of ACA has risen in recent years, and ACA now accounts for approximately 20% of invasive cervical cancers in the screened populations worldwide. OBJECTIVE: To compare the epidemiological, clinical characteristics, and treatment outcomes of ACA with those of SCC of the cervix in a sub-optimally screened population. METHODS: Data from cervical cancer patients with SCC and ACA treated from 2000 through 2009 were obtained from the Brazilian Hospital Cancer Register databases. The summary odds ratios and chi-square tests were estimated. RESULTS: A total of 51,842 patients including 45,540 (87.8%) cases of SCC and 6302 (12.2%) of ACA were analyzed. Compared with the ACA patients, the SCC patients were younger and more frequently black and had a higher degree of illiteracy and alcohol and tobacco consumers. The tumor stage at the time of diagnosis was also significantly different between the two groups. However, initial therapeutic response and death rate after the first course of treatment were similar in both groups. CONCLUSIONS: Differences between ACA and SCC were observed for all demographic and clinical variables analyzed but not for responses to treatment and death at the end of the first course of treatment. Irrespective of the histological subtype, the quality of screening and treatment must be improved in developing countries, since initial therapeutic response of ACA and SCC is similar. PMID- 25130678 TI - In a randomized, double-blind clinical trial, adjuvant atorvastatin improved symptoms of depression and blood lipid values in patients suffering from severe major depressive disorder. AB - BACKGROUND: The administration of statins seems to be a promising new avenue in the treatment of patients suffering from major depressive disorder (MDD), though patients suffering from severe MDD remain unstudied in this respect. The aim of the present study was therefore to investigate, in a randomized double-blind clinical trial, the influence of adjuvant atorvastatin on symptoms of depression in patients with MDD. METHODS: A total of 60 patients suffering from MDD (mean age: 32.25 years; 53% males) received a standard medication of 40 mg/d citalopram. Next, patients were randomly assigned either to the atorvastatin group (20 mg/d) or to the placebo group. Blood lipid values were assessed at baseline and on completion of the study 12 weeks later. Experts rated depressive symptoms via Hamilton Depression Rating Scales (HDRS) at baseline and 3, 6 and 12 weeks later. RESULTS: HDRS scores decreased over time; the significant Time by Group interaction showed that symptoms of depression decreased more in the atorvastatin than in the placebo group. Compared to the placebo group, in the atorvastatin group cholesterol, triglyceride, and Low Density Lipids (LDL) significantly decreased, and High Density Lipids (HDL) significantly increased over time. HDRS scores and blood lipid values were generally not associated. CONCLUSIONS: The pattern of results suggests that adjuvant atorvastatin favorably influences symptoms of depression among patients with severe MDD. Given that after 12 weeks of monotherapy and adjuvant atorvastatin patients were still moderately to severely depressed, more powerful treatment algorithms such as augmentation and change of medication are highly recommended. PMID- 25130679 TI - The growing epidemic of water pipe smoking: health effects and future needs. AB - Water pipe smoking (WPS), an old method of tobacco smoking, is re-gaining widespread popularity all over the world and among various populations. Smoking machine studies have shown that the water pipe (WP) mainstream smoke (MSS) contains a wide array of chemical substances, many of which are highly toxic and carcinogenic for humans. The concentrations of some substances exceed those present in MSS of cigarettes. Despite being of low grade, current evidence indicates that WPS is associated with different adverse health effects, not only on the respiratory system but also on the cardiovascular, hematological, and reproductive systems, including pregnancy outcomes. In addition, association between WPS and malignancies, such as lung, oral and nasopharyngeal cancer, has been suggested in different studies and systematic reviews. Despite its long standing history, WPS research still harbors a lot of deficiencies. The magnitude of toxicants and carcinogen exposures, effects on human health, as well as the addiction and dependence potentials associated with WPS need to be studied in well-designed prospective trials. Unfortunately, many of the tobacco control and clean indoor policies have exempted water pipes. World wide awareness among the public, smokers, and policymakers about the potential health effects of WPS is urgently required. Furthermore, stringent policies and laws that control and ban WPS in public places, similar to those applied on cigarettes smoking need to be implemented. PMID- 25130680 TI - A simple rule to identify patients with chronic obstructive pulmonary disease who may need treatment reevaluation. AB - BACKGROUND: A simple rule based on short-acting inhaled beta2-agonist (SABA) use could identify patients with chronic obstructive pulmonary disease (COPD) at increased risk of exacerbations and signal the need for maintenance therapy change, similar to asthma "Rules of Two((r))". METHODS: Associations between SABA use, COPD exacerbations, and health care costs over 1 year were examined retrospectively using de-identified patient data from the Optum Research Database (ORD; N = 56,581) and the Impact National Benchmark Database (IMPACTTM; N = 9423). Nebulized and metered-dose inhaler (MDI) SABA doses were normalized to 2.5 mg and 90 mcg albuterol equivalents, respectively. RESULTS: The GOLD initiative establishes >=2 exacerbations/year as indicative of increased risk in COPD. We identified a correlation (p < 0.0001) between 1.5 SABA doses/day and this frequency of exacerbations. In ORD, patients using >=1.5 versus <1.5 SABA doses/day experienced significantly more exacerbations: 1.92 (95% confidence interval [CI], 1.89-1.96) versus 1.36 (95% CI, 1.34-1.38) per patient year (PPY). Above-threshold use was associated with higher average annual COPD-related costs (2010 $US): $21,868 (standard deviation [SD], $53,910) versus $11,686 (SD, $32,707) for nebulized SABA only, $9216 (SD, $30,710) versus $7334 (SD, $24,853) for MDI SABA only, and $15,806 (SD, $35,260) versus $11,233 (SD, $27,006) for both nebulized and MDI SABA. IMPACTTM validated these findings. CONCLUSION: Patients with COPD using >=1.5 SABA doses/day were at increased risk of exacerbations. Our results suggest a "Rule of 3-2": SABA use >=3 times in 2 days should be considered a clinical marker for needing treatment reevaluation. PMID- 25130681 TI - Getting going and letting go: Religiosity fosters opportunity-congruent coping with work-related uncertainties. AB - This study investigated how religiosity relates to goal engagement (i.e., investing time and effort; overcoming obstacles) and goal disengagement (i.e., protecting self-esteem and motivational resources against failure experiences; distancing from unattainable goals) in coping with perceived work-related uncertainties (e.g., growing risk of job loss) that arise from current social change. We hypothesised that religiosity not only expands individuals' capacities for both engagement and disengagement but also fosters an opportunity-congruent pattern of engagement and disengagement, promoting engagement especially under favourable opportunities for goal-striving in the social ecology and facilitating disengagement especially under unfavourable opportunities. Multilevel analyses in a sample of N = 2089 Polish adults aged 20-46 years partly supported these predictions. Religiosity was associated with higher goal engagement, especially under favourable economic opportunities for goal-striving in the social ecology (as measured by the regional net migration rate). For disengagement, the results were more mixed; religiosity was related to higher self-protection independently of the economic opportunity structure and predicted higher goal-distancing only under the most unfavourable opportunities. These results suggest that religiosity can promote different coping strategies under different conditions, fostering a pattern of opportunity-congruent engagement and, to some extent, disengagement that is likely to be adaptive. PMID- 25130682 TI - How can weight-loss app designers' best engage and support users? A qualitative investigation. AB - OBJECTIVES: This study explored young adults' experiences of using e-health internet-based computer or mobile phone applications (apps) and what they valued about those apps. DESIGN AND METHODS: A qualitative design was used. Semi structured interviews were conducted with a community sample of 19 young adults who had used a publicly available phone or internet-based application. Transcripts were analysed using thematic analysis. RESULTS: Participants valued an attractive user interface. Structure, ease of use, personalised features and accessibility (including dual phone-computer access) were all important to participants and users indicated that continued use depended on these design features. Many believed that a focus on calorie counting was too limiting. Some users mentioned behaviour change strategies and known behaviour change techniques utilised by apps including; self-monitoring, goal setting and behavioural feedback. Only a few users reported positive changes in physical activity levels. CONCLUSIONS: Use of particular design features and application of evidence-based behaviour change techniques could optimise continued use and the effectiveness of internet/smart phone interventions. Statement of contribution What is already known on this subject? E-health is increasingly used to deliver weight loss/control programs. Most e-health programs have not been founded on evidence based designs and it is unclear what features and functions users find useful or not so useful. What does this study add? Weight loss app users valued structure, ease of use, personalised features and accessibility. Goal setting and feedback on calorie intake/energy balance were the most widely used behaviour change techniques. Designers should consider an extensive food database, a food scanner, and provision of diaries. PMID- 25130683 TI - Expression of costimulatory molecule B7-H3 and its prognostic implications in human acute leukemia. AB - OBJECTIVES: This study focused on the expression pattern and clinical significance of B7-H3 expression in human acute leukemia. METHODS: We systematically analyzed 134 patients with acute myeloid leukemia (101 cases) and acute lymphocytic leukemia (33 cases) by flow cytometry. RESULTS: The frequency of B7-H3(+) cases was 44.8% in total. The B7-H3 expression rate differed from 0% to 74.8% in individual cases. The correlation between B7-H3 expression and traditional prognostic factors, such as age and gender, the white blood cell count was not confirmed. However, B7-H3 had a significant higher expression in CD34(+) cases and high risk karyotypes. CONCLUSIONS: Owing to the expression of B7-H3 being statistically relevant in predicting disease progression and a shorter life survival, our results demonstrated that B7-H3 expression in acute leukemia predicts an unfavorable outcome. PMID- 25130685 TI - Nutrition of the captive western lowland gorilla (Gorilla gorilla gorilla): a dietary survey. AB - The successful management of captive animals requires attention to multiple interconnected factors. One critical aspect of the daily life of a captive animal is the recommended and/or provisioned diet. This study focuses on the diets of zoo-housed gorillas. A national survey of diets among zoo-housed gorillas was conducted to examine diets being offered to captive gorillas in the United States and Canada. This survey serves as a follow-up to a 1995 dietary survey of zoo housed gorillas and goes further to quantify nutritional profiles at responding institutions. Results are encouraging, as zoos have made clear improvements in dietary nutrient profiles offered over the past 15 years. However, we suggest that zoological and sanctuary institutions follow Gorilla Species Survival Plan (SSP) recommendations and work to continuously improve diets provided, which could improve gorillas' health and well-being. PMID- 25130684 TI - Gestational diabetes mellitus modulates neonatal high-density lipoprotein composition and its functional heterogeneity. AB - Gestational diabetes mellitus (GDM) is related to neonatal macrosomia and an increased risk of vascular events. We hypothesized that GDM exerts qualitative effects on neonatal high-density lipoprotein (HDL). HDL was isolated from control (n=11) and GDM maternal/neonatal donors (n=9) and subjected to shotgun proteomics. Differences in HDL mobility were assessed by FPLC and native gel electrophoresis. Paraoxonase (PON1) activity, cholesterol ester-transfer protein (CETP) mass and activity, phospholipid, triglyceride and cholesterol concentrations were quantified with commercial kits. Total anti-oxidative capacity and cholesterol efflux capability of HDLs were measured. Four proteins involved in lipid metabolism, inflammation and innate immunity were differentially expressed between controls and GDM neonates. ApoM (decreased, p<0.05) and SAA1 (increased, p<0.05) showed the same differences on both, maternal and neonatal GDM HDL. Lower PON1 protein expression was corroborated by lower activity (p<0.05) which in turn was associated with attenuated anti-oxidant capacity of GDM HDL. Protein changes were accompanied by increased levels of triglycerides and decreased levels of cholesterol esters, respectively. The observed differences in GDM HDL lipid moiety may be related to CETP mass and activity alterations. The rate of cholesterol efflux from term trophoblasts to maternal and from placental endothelial cells to neonatal GDM HDL was impaired (p<0.05). In conclusion, GDM causes changes in HDL composition and is intimately associated with impaired cholesterol efflux capability as well as diminished anti oxidative particle properties. Remodeling of neonatal GDM HDL in utero supports the hypothesis that maternal conditions in pregnancy impact neonatal lipoprotein metabolism. PMID- 25130687 TI - The social media revolution is changing the conference experience: analytics and trends from eight international meetings. AB - OBJECTIVE: To analyse the use of Twitter at urology conferences to enhance the social media conference experience. MATERIALS AND METHODS: We prospectively registered the hashtags of eight international urology conferences taking place in 2013, using the social media metrics website, Symplur.com. In addition, we prospectively registered the hashtag for the European Association of Urology (EAU) Annual Congress for 3 consecutive years (2012-2014) to analyse the trend in the use of Twitter at a particular meeting. Metrics including number of 'tweets', number of participants, tweet traffic per day, and overall digital impressions, which were captured for 5 days before each conference, the conference itself, and the following 2 days. We also measured corresponding social media activity at a very large non-urology meeting (the American Society of Clinical Oncology) for comparative purposes. RESULTS: Twitter activity was noted at all eight conferences in 2013. In all, 12,363 tweets were sent generating over 14 million impressions. The number of participants tweeting at each meeting varied from 80 (Congress of the Societe Internationale d'Urologie, #SIU2013) to 573 (the American Urological Association, #AUA13). Overall, the AUA meeting (#AUA13) generated the most Twitter activity with >8.6 million impressions and a total of 4663 tweets over the peri-conference period. It also had the most impressions and tweets per day over this period, at 717,000 and 389, respectively. The EAU Annual Congress 2013 (#EAU13) generated 1.74 million impressions from a total of 1762 tweets from 236 participants. For trends in Twitter use, there was a very sharp rise in Twitter activity at the EAU Annual Congress between 2012 and 2014. Over this 3-year period, the number of participants increased almost 10-fold, leading to an increase in the number of tweets from 347 to almost 6000. At #EAU14, digital impressions reached 7.35 million with 5903 tweets sent by 797 participants. CONCLUSIONS: Urological conferences, to a varying extent, have adopted social media as a means of amplifying the conference experience to a wider audience, generating international engagement and global reach. Twitter is a very powerful tool that amplifies the content of scientific meetings, and conference organisers should put in place strategies to capitalise on this. PMID- 25130686 TI - Migration and differentiation of gonadal germ cells under cross-sex germline chimeras condition in domestic chickens. AB - A series of experiments was conducted to investigate migration, proliferation and differentiation of gonadal germ cells (GGCs) collected from the gonads of 7-day old chick embryos under cross-sex germline chimera conditions. The migratory and proliferative abilities of exogenous GGCs were examined by transferring 50 fluorescently labeled GGCs collected from White Leghorn (WL) embryos into the blood of 2-day-old Rhode Island Red (RIR) embryos. No significant difference was observed in the number of fluorescently labeled GGCs in the gonads of recipient embryos among any of the four possible donor and recipient sex combinations. Cross-sex germline chimeras were produced to examine the differentiation of GGCs by transferring 100 GGCs from WL embryos into 2-day-old RIR embryos. Exogenous GGC-derived progeny were obtained from both male and female recipients, except when female GGCs were transferred into male recipients. The migratory ability of GGCs recovered from the 7-day-old embryonic gonad was not influenced by cross-sex germ cell transfer conditions, whereas the differentiation of the GGCs was affected by the sex combinations of GGCs donors and recipients. PMID- 25130688 TI - Prognostic factors in adolescent and adult patients with acute lymphoblastic leukemia with two protocols of chemotherapy: a cross-sectional study. AB - BACKGROUND: We evaluated the clinical, laboratory, and prognostic factors in adolescent and adult patients with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: In this observational, retrospective, cross-sectional study, we examined the medical records of all consecutive patients with ALL admitted to a public hospital in Brazil from 1990 to 2005. RESULTS: Of the 102 patients included, 88 were treated with 2 protocols of chemotherapy (Berlin-Frankfurt Munster [BFM] 86 modified [BFM-86M] and UCLA [University of California, Los Angeles] protocol). The complete remission (CR), disease-free survival, and overall survival (OS) rate was 70.6%, 27%, and 30.5%, respectively (median follow up, 49 months). Age < 18 years and no leukemic infiltration in the central nervous system (CNS) at diagnosis were positively associated with CR (P = .03); no bleeding and hepatomegaly at diagnosis and age < 35 years were associated with better OS on multivariate analyses of the whole population (P = .01). OS at 4 years was superior with BFM-86M than with UCLA (49.5% vs. 16%; P = .004), especially in young adults without risk factors. CONCLUSION: We identified age as the most important prognostic factor in patients with ALL. CNS infiltration, hepatomegaly, and bleeding were associated with lower OS but must be validated in future research with South American populations and worldwide. The BFM-86M protocol can be considered a therapeutic option for young adults (age < 35 years) without adverse prognostic factors. For other patients with ALL, we emphasize the need for different therapeutic approaches. PMID- 25130689 TI - An orthogonal click-chemistry approach to design poly(glycerol monomethacrylate) based nanomaterials for controlled immunostimulation. AB - A versatile approach is proposed for the synthesis of novel immunoactive nanomaterials based on biocompatible poly(glycerol monomethacrylate) (PGMMA). Propargyl-terminated PGMMA is synthesized via atom transfer radical polymerization and then modified through the introduction of dangling acrylate groups, at controlled degree of functionalisation. Acrylates are then able to react quantitatively with thiols, such as immunoactive thiomannose, through Michael-type addition under mild conditions and at a physiologically acceptable pH. The terminal propargyl group can be modified independently with azide end capping groups and it is utilized to graft the macromolecules to a fluorescent dye. The resulting mannose-linked PGMMAs confirm a safe cytotoxic profile and are able to stimulate cytokine production (TNFalpha), membrane protein expression (CD40), and cellular uptake in bone marrow derived dendritic cells. Cell stimulation is dependent on the mannose content and enhanced by serum proteins, suggesting a role for mannose-binding receptors and/or complement receptors in the cell membrane. PMID- 25130693 TI - The biology of Mur ligases as an antibacterial target. AB - With antibiotic resistance mechanisms increasing in diversity and spreading among bacterial pathogens, the development of new classes of antibacterial agents against judiciously chosen targets is a high-priority task. The biochemical pathway for peptidoglycan biosynthesis is one of the best sources of antibacterial targets. Within this pathway are the Mur ligases, described in this review as highly suitable targets for the development of new classes of antibacterial agents. The amide ligases MurC, MurD, MurE and MurF function with the same catalytic mechanism and share conserved amino acid regions and structural features that can conceivably be exploited for the design of inhibitors that simultaneously target more than one enzyme. This would provide multi-target antibacterial weapons with minimized likelihood of target-mediated resistance development. PMID- 25130694 TI - Hibernation alters the diversity and composition of mucosa-associated bacteria while enhancing antimicrobial defence in the gut of 13-lined ground squirrels. AB - The gut microbiota plays important roles in animal nutrition and health. This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. Communities in all seasons were dominated by Firmicutes and Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. Hibernation also decreased caecal TLR4 and increased TLR5 expression, suggesting a protective response that minimizes inflammation. PMID- 25130696 TI - A novel method for autograft placement during tegmen repair: the suture "pull through" technique. PMID- 25130695 TI - Sequential gene silencing using wavelength-selective caged morpholino oligonucleotides. AB - Spectrally differentiated caged morpholino oligonucleotides (cMOs) and wavelength selective illumination have been used to sequentially inactivate organismal gene function. The efficacy of these reverse-genetic chemical probes has been demonstrated in zebrafish embryos, and these reagents have been employed to examine the mechanisms of mesoderm patterning. PMID- 25130697 TI - Residence-time dependent cell wall deformation of different Staphylococcus aureus strains on gold measured using surface-enhanced-fluorescence. AB - Bacterial adhesion to surfaces is accompanied by cell wall deformation that may extend to the lipid membrane with an impact on the antimicrobial susceptibility of the organisms. Nanoscale cell wall deformation upon adhesion is difficult to measure, except for Deltapbp4 mutants, deficient in peptidoglycan cross-linking. This work explores surface enhanced fluorescence to measure the cell wall deformation of Staphylococci adhering on gold surfaces. Adhesion-related fluorescence enhancement depends on the distance of the bacteria from the surface and the residence-time of the adhering bacteria. A model is forwarded based on the adhesion-related fluorescence enhancement of green-fluorescent microspheres, through which the distance to the surface and cell wall deformation of adhering bacteria can be calculated from their residence-time dependent adhesion-related fluorescence enhancement. The distances between adhering bacteria and a surface, including compression of their extracellular polymeric substance (EPS)-layer, decrease up to 60 min after adhesion, followed by cell wall deformation. Cell wall deformation is independent of the integrity of the EPS-layer and proceeds fastest for a Deltapbp4 strain. PMID- 25130699 TI - Abstracts of the SMART STROKES 2014 Conference, 28-29 August, 2014, Sydney, NSW, Australia. PMID- 25130698 TI - miR-639 regulates transforming growth factor beta-induced epithelial-mesenchymal transition in human tongue cancer cells by targeting FOXC1. AB - Epithelial-to-mesenchymal transition (EMT) is implicated in embryonic development and various pathological events. Transforming growth factor beta (TGFbeta) has been reported to induce EMT in tumor cells, which is a critical step in the process of metastasis leading to cancer spreading and treatment failure. However, the involvement of microRNA during the EMT process in tongue squamous cell carcinoma (TSCC) remains to be determined. To address this question, TSCC cell lines SCC9 and CAL27 were treated with human recombinant TGFbeta1 for 48 h. miRNA microarray illustrated that miR-639 was significantly downregulated in TGFbeta treated SCC9 cells. Ectopic expression of miR-639 with miRNA mimics effectively blocked TGFbeta-induced EMT in SCC9 and CAL27 cells, but inhibition of miR-639 in SCC9 and CAL27 cells with antisense oligonucleotides induced EMT. Computational microRNA target predictions detected a conserved sequence matching to the seed region of miR-639 in the 3'-UTR of FOXC1 mRNA. Luciferase reporter assays revealed that miR-639 targets FOXC1. Ectopic expression of FOXC1 induces EMT in TSCC cells. Silencing FOXC1 expression blocked TGFbeta-induced EMT in SCC9 cells. Clinically, reduced miR-639 expression was associated with metastasis in TSCC and poor patient survival. The data from the present study suggest that reduced expression of miR-639 underscores the mechanism of TGFbeta-induced EMT in TSCC by targeting FOXC1 and may serve as therapeutic targets in the process of metastasis. PMID- 25130700 TI - Functionalization of cantilever tips with nucleotides by the phosphoramidite method. AB - In atomic force microscopy (AFM) a sharp cantilever tip is used to scan surfaces at the atomic level. One further application is force spectroscopy, in which force-distance curves between binding partners located on the cantilever and substrate surface are determined. This requires specifically immobilized molecules. Herein we describe the covalent binding of single adenosine and thymidine nucleotides on an amino-PEGylated cantilever tip by the phosphoramidite method. Force-distance curves between these cantilever tips and gold surfaces were recorded. The rupture forces of the coordination bond between the primary amine of adenosine and the undercoordinated gold atoms were determined to be 145 pN, which is in agreement with previously published data. The force-distance curves of thymidine-functionalized tips did not show rupture events, because this nucleotide does not possess a primary amine function. Nucleotide-functionalized tips could aid in the understanding of binding mechanisms of nucleotide binding molecules such as polymerases immobilized on surfaces or membranes. PMID- 25130702 TI - Marker genes for the metabolic adaptation of Pseudomonas aeruginosa to the hypoxic cystic fibrosis lung environment. AB - Pseudomonas aeruginosa is the leading pathogen of chronic cystic fibrosis (CF) lung infection. Life-long persistence in the inflamed and ever fluctuating CF lungs results in the selection of a variety of changes in P. aeruginosa physiology. Accumulating evidence suggests that especially metabolic changes support the survival and growth of P. aeruginosa within the hypoxic and nutritious CF mucus. To investigate if metabolic adaptations we described for hypermutable P. aeruginosa from late CF lung disease (Hoboth et al., 2009. J. Infect. Dis., pp. 118-130) may represent specific changes in response to the selective conditions within the oxygen-restricted CF mucus, we determined the expression of a set of genes during aerobic and hypoxic growth in LB and the artificial sputum medium ASM. We further focused on the regulation of the two isocitrate dehydrogenases Icd and Idh. Interestingly, both isoenzymes may replace each other under aerobic and hypoxic conditions. The NADPH- and RpoS-dependent Icd seems to be the leading isoenzyme under prolonged oxygen limitation and stationary growth phase. LacZ reporter analysis revealed that oxygen-restriction increased the expression levels of azu, cbb3-1, cbb3-2, ccpR, icd, idh and oprF gene, whereas himD and nuoA are increasingly expressed only during hypoxic growth in ASM. Overexpression of the anaerobic regulator Anr improved the expression of azu, ccpR, cbb3-2 and icd. In summary, expression of azu, cbb3-1, cbb3-2, ccpR, icd, idh, oprF, himD, and nuoA appeared to be beneficial for the growth of P. aeruginosa under hypoxic conditions indicating these genes may represent marker genes for the metabolic adaptation to the CF lung environment. PMID- 25130703 TI - Risk factors for MRSA infection in companion animals: results from a case-control study within Germany. AB - Increasing numbers of companion animals suffering from infections with methicillin-resistant Staphylococcus aureus (MRSA) have been reported in the recent past. These infections are of particular concern because of the limited treatment options for MRSA and their transferability to humans. Since MRSA lineages isolated from infected companion animals often mirror typical human epidemic strains circulating in the same region, successful strategies to combat MRSA need strong and coordinated efforts from both, the human and the veterinary field according to the "One Health" concept. Hence, to identify potential risk factors related to MRSA infections in dogs, cats and horses, a case-control study was conducted, including data on 106 MRSA-infected animal patients as cases and 102 MSSA-infected animals as controls, originating from 155 different veterinary settings within Germany. Demographic data on animal patients, patient history and administration of antibiotics as well as practice/clinic specific parameters were assessed as putative risk factors. Multivariable logistic regression identified the following variables as risk factors for MRSA infection compared to MSSA infection: number of employees working at the veterinary setting (n>10; p<0.001), antibiotic treatment prior to sampling (systemic: p=0.002; local: p=0.049, both: p=0.011) and surgical site infection (p<0.001). Spa typing revealed predominantly clonal complexes well-known for hospital-associated lineages spreading in human health-care settings in Germany (CC5 and CC22) for isolates of dog and cat origin. CC398-MRSA dominated among equine isolates, a CC that was described as a nosocomial pathogen in equine clinical settings before. The identified risk factors and genotyping results are in accordance with numerous study outcomes from the field of human medicine and point towards reasonable problems with nosocomial spread of MRSA, especially within companion animal veterinary clinics. To define targeted infection control strategies against nosocomial pathogens, it is important to accomplish intervention studies addressing routes of transmission in companion animal veterinary settings. PMID- 25130701 TI - The effects of the pharmaceutical carbamazepine on life history characteristics of flat-headed mayflies (Heptageniidae) and aquatic resource interactions. AB - Pharmaceutical pollutants are commonly detected in freshwater ecosystems around the world and have biological effects on aquatic organisms. However, current understanding of the influence this contaminant class has on freshwater communities and ecosystems is lacking. Recently the scientific community has called for research focusing on certain pharmaceuticals due to their ubiquity and potential toxicity. Carbamazepine is one of these pharmaceuticals. To better understand the effect carbamazepine has on life history characteristics of aquatic organisms and consumer-resource interactions, we quantified the influence of carbamazepine on the development, growth and behavior of mayfly nymphs (Stenonema sp.) and the alterations in food consumer-resource interactions between Stenonema and algae (Chaetophora). Microcosms were assembled in a factorial design containing algae and mayfly nymphs native to central Indiana and dosed with environmentally relevant concentrations of carbamazepine. From this ecotoxicological experiment we were able to infer that carbamazepine at 2,000 ng/L influenced the development and behavior of Stenonema nymphs and the body dimensions of adult individuals. However, it appears that carbamazepine does not influence consumer-resource interactions at concentrations found in surface waters. The pharmaceutical carbamazepine may influence the behavior, growth and development of mayflies, which could have significant consequences at the population, community and ecosystem level. PMID- 25130704 TI - Cost-effectiveness of red blood cell transfusion vs. non-intervention in women with acute anaemia after postpartum haemorrhage. AB - BACKGROUND: Red blood cell (RBC) transfusion is frequently used to treat women with acute anaemia after postpartum haemorrhage. We aimed to assess the economic consequences of red blood cell transfusion compared to non-intervention in these women. METHODS: A trial-based cost-effectiveness analysis was performed alongside the Well-Being of Obstetric patients on Minimal Blood transfusions (WOMB) trial. Women with acute anaemia [Hb 4.8-7.9 g/dl (3.0-4.9 mm)] after postpartum haemorrhage, without severe anaemic symptoms, were randomly allocated to RBC transfusion or non-intervention. Primary outcome of the trial was physical fatigue (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Total costs per arm were calculated using a hospital perspective with a 6 weeks time horizon. RESULTS: Per woman, mean costs in the RBC transfusion arm (n = 258) were ?1957 compared to ?1708 in the non-intervention arm (n = 261; P = 0.024). The 13% difference in costs between study arms predominantly originated from costs of RBC units, as costs of RBC units were six times higher in the RBC transfusion arm. RBC transfusion led to a small improvement in physical fatigue of 0.58 points per day; thus, the costs to improve the physical fatigue score with one point would be ?431. CONCLUSION: In women with acute anaemia after postpartum haemorrhage (PPH), RBC transfusion is on average ?249 more expensive per woman than non-intervention, with only a small gain in HRQoL after RBC transfusion. Taking both clinical and economic consequences into account, implementation of a non-intervention policy seems justified. PMID- 25130706 TI - Exchange-coupled nanocomposites: chemical synthesis, characterization and applications. AB - Nanocomposites containing soft and hard magnetic phases have attracted immense attention for energy-related and biomedical applications. With exchange coupling between nanoscale grains in the composites, magnetization of the soft magnetic phase can rotate coherently with that of the hard magnetic phase. In particular, good control of the soft and hard phases at the nanoscale in the composites is of great importance for effective exchange coupling, allowing us to make the best of the strengths of soft and hard magnetic phases and to optimize the magnetic properties for targeted applications. In this review, we present the recent progress in the chemical synthesis and applications of exchange-coupled nanocomposites. Firstly, the principle of nanomagnetism and exchange coupling is introduced. Secondly, the characterization of exchange-coupled nanocomposites is summarized. Thirdly, the chemical methods for the production of different exchange-coupled nanocomposites are presented. Finally, applications of exchange coupled nanocomposites in magnetic energy storage and biomedicine are addressed. PMID- 25130705 TI - Minimally invasive fetal autopsy using ultrasound: a feasibility study. AB - OBJECTIVES: To evaluate postmortem ultrasound (PM-US) for minimally invasive autopsy, and to demonstrate its feasibility, sensitivity and specificity, as compared with conventional autopsy, in detecting major congenital abnormalities. METHODS: Over a 19-month study period from 1 March 2012 to 30 September 2013, we recruited from a referral hospital 88 consecutive fetuses, at 11-40 weeks' gestation, which had undergone termination, miscarriage or intrauterine fetal death. We performed PM-US using different transducers and compared the data with those from conventional autopsy. The latter was performed, according to the Societe Francaise de Foetopathologie (France) guidelines, by experienced perinatal pathologists who were blinded to the ultrasound data. RESULTS: Complete virtual autopsy by ultrasound was possible in 95.5% of the cases. The sensitivity of PM-US for detecting brain abnormalities was 90.9% (95% CI, 58.7-99.8%) and the specificity was 87.3% (95% CI, 75.5-94.7%). In 20% of cases, a neuropathological examination was not possible due to severe maceration. The sensitivity for detection of thoracic abnormalities was 88.9% (95% CI, 65.3-98.6%) and the specificity was 92.8% (95% CI, 84.1-97.6%), and the sensitivity for detection of abdominal anomalies was 85.7% (95% CI, 57.2-98.2%) and the specificity was 94.6% (95% CI, 86.7-98.5%). CONCLUSION: This pilot study confirms the feasibility of PM US for virtual autopsy as early as 11 weeks' gestation. This new technique shows high sensitivity and specificity in detecting congenital structural abnormalities as compared with conventional autopsy. Copyright (c) 2014 ISUOG. Published by John Wiley & Sons Ltd. PMID- 25130707 TI - Predictors of men's sexual response to erotic film stimuli: the role of affect and self-reported thoughts. AB - INTRODUCTION: Both emotions and cognitions seem to play a role in determining sexual arousal. However, no studies to date have tested the effects of self reported thoughts on subjective sexual arousal and genital response using psychophysiological methods. AIM: The aim of the present study was to evaluate the role of self-reported thoughts and affect during exposure to erotic material in predicting subjective and genital responses in sexually healthy men. METHODS: Twenty-seven men were presented with two explicit films, and genital responses, subjective sexual arousal, self-reported thoughts, and positive and negative affect were assessed. MAIN OUTCOME MEASURES: Men's genital responses, subjective sexual arousal, affective responses, and self-reported thoughts during exposure to sexual stimulus were measured. RESULTS: Regression analyses revealed that genital responses were predicted by self-reported thoughts (explaining 20% of the variance) but not by affect during exposure to erotic films. On the other hand, subjective sexual arousal was significantly predicted by both positive and negative affect (explaining 18% of the variance) and self-reported thoughts (explaining 37% of the variance). Follow-up analyses using the single predictors showed that "sexual arousal thoughts" were the only significant predictor of subjective response (beta = 0.64; P < 0.01) and that "distracting/disengaging thoughts" were the best predictor of genital response (beta = -0.51; P < 0.05). CONCLUSIONS: The findings of this study suggest that both affect and sexual arousal thoughts play an important role in men's subjective sexual response, whereas genital response seems to be better predicted by distracting thoughts. PMID- 25130708 TI - Nanotube aerogel sheet flutter for actuation, power generation, and infrasound detection. AB - Electromagnetic induction (EMI) is a mechanism of classical physics that can be utilized to convert mechanical energy to electrical energy or electrical to mechanical energy. This mechanism has not been exploited fully because of lack of a material with a sufficiently low force constant. We here show that carbon nanotube (CNT) aerogel sheets can exploit EMI to provide mechanical actuation at very low applied voltages, to harvest mechanical energy from small air pressure fluctuations, and to detect infrasound at inaudible frequencies below 20 Hz. Using conformal deposition of 100 nm thick aluminum coatings on the nanotubes in the sheets, mechanical actuation can be obtained by applying millivolts, as compared with the thousand volts needed to achieve giant-stroke electrostatic actuation of carbon nanotube aerogel sheets. Device simplicity and performance suggest possible applications as an energy harvester of low energy air fluctuations and as a sensor for infrasound frequencies. PMID- 25130709 TI - Simultaneous KIT mutation and succinate dehydrogenase (SDH) deficiency in a patient with a gastrointestinal stromal tumour and Carney-Stratakis syndrome: a case report. PMID- 25130710 TI - Prediction of the net energy value of broiler diets. AB - Thirty pelleted diets were given to broiler chickens (eight birds per diet; 21 to 35 days of age) for individual in vivo measurements of dietary net energy (NE) value, using three trials with 10 diets/trial. Amino acid formulation of diets was done on the basis of ratios to CP. NE was measured according to the body analysis method. The basal metabolism component of NE values was calculated on the basis of mean metabolic weight using a coefficient obtained in a previous experiment. Information about apparent metabolisable energy (AME) value of diets, AME corrected to zero nitrogen retention (AMEn) and digestibilities of proteins, lipids, starch and sugars was available from a previous publication. In each trial, mean NE/AME ratios of diets varied by about 6%. From the multiple regressions (n=30) expressing NE and AMEn values as functions of digestible component contents, it was deduced that the NE/AMEn ratios assigned to dietary components were 0.760, 0.862, 0.806, 0.690 and 0.602 for CP, lipids, starch, (sucrose+glucose) and fermentable sugars (alpha-galacto-oligosaccharides and lactose), respectively. The NE/AME ratio of CP was 0.680. Regression calculations showed that the NE values assigned to individual birds (n=240) could also be predicted with diet AMEn values (NE=0.80 AMEn; R 2=0.770) or with an equation combining AMEn value and CP/AMEn ratio (R 2=0.773). The latter ratio was found to be the only additional parameter that was significant when added in the NE regression scheme based on AMEn. PMID- 25130711 TI - Changes in plasma leptin concentration during different types of exercises performed by horses. AB - Leptin is a tissue-derivative adipokine that regulates appetite, food intake and energy expenditure. It is still not clear how exercise affects plasma leptin concentration in horses. The aim of this study was to evaluate the influence of exercise intensity and duration on plasma leptin levels in working horses. A total of 38 horses were prospectively included in the study and grouped according to the type of exercise they performed: dressage (six stallions, group D), jumping (12 stallions, group J), race (12 Thoroughbred horses, six stallions and six mares, group R) and harness (10 light draft stallions, group H). Blood samples were taken both before and after routine exercise (immediately after the exercise, 30 min and 24 h after). Blood lactic acid (LA) and plasma concentration of leptin, cortisol, uric acid, triacylglycerols, glycerol and free fatty acids were determined. Immediately after exercise, group R had the highest level of LA, whereas groups D and J had the lowest levels. A significant increase in plasma leptin concentration was stated only in group H in samples taken immediately after the end of the exercise period and 30 min after the exercise period, as compared with the values obtained at rest. A significant increase in plasma cortisol concentration was found immediately after the end of the exercise period in groups R and H. Leptin exercise-to-rest ratio was significantly correlated with cortisol exercise-to-rest ratio (r=0.64; P<0.001). The increase in plasma leptin concentration in exercised horses was related to the increased plasma cortisol concentration and took place only during long-lasting exercise, which was not intensive. PMID- 25130712 TI - Injurious tail biting in pigs: how can it be controlled in existing systems without tail docking? AB - Tail biting is a serious animal welfare and economic problem in pig production. Tail docking, which reduces but does not eliminate tail biting, remains widespread. However, in the EU tail docking may not be used routinely, and some 'alternative' forms of pig production and certain countries do not allow tail docking at all. Against this background, using a novel approach focusing on research where tail injuries were quantified, we review the measures that can be used to control tail biting in pigs without tail docking. Using this strict criterion, there was good evidence that manipulable substrates and feeder space affect damaging tail biting. Only epidemiological evidence was available for effects of temperature and season, and the effect of stocking density was unclear. Studies suggest that group size has little effect, and the effects of nutrition, disease and breed require further investigation. The review identifies a number of knowledge gaps and promising avenues for future research into prevention and mitigation. We illustrate the diversity of hypotheses concerning how different proposed risk factors might increase tail biting through their effect on each other or on the proposed underlying processes of tail biting. A quantitative comparison of the efficacy of different methods of provision of manipulable materials, and a review of current practices in countries and assurance schemes where tail docking is banned, both suggest that daily provision of small quantities of destructible, manipulable natural materials can be of considerable benefit. Further comparative research is needed into materials, such as ropes, which are compatible with slatted floors. Also, materials which double as fuel for anaerobic digesters could be utilised. As well as optimising housing and management to reduce risk, it is important to detect and treat tail biting as soon as it occurs. Early warning signs before the first bloody tails appear, such as pigs holding their tails tucked under, could in future be automatically detected using precision livestock farming methods enabling earlier reaction and prevention of tail damage. However, there is a lack of scientific studies on how best to respond to outbreaks: the effectiveness of, for example, removing biters and/or bitten pigs, increasing enrichment, or applying substances to tails should be investigated. Finally, some breeding companies are exploring options for reducing the genetic propensity to tail bite. If these various approaches to reduce tail biting are implemented we propose that the need for tail docking will be reduced. PMID- 25130713 TI - Adolescent Motivations to Engage in Pro-Social Behaviors and Abstain From Health Risk Behaviors: A Self-Determination Theory Approach. AB - The present study used self-determination theory to examine adolescents' motivations to engage in charitable donating and community volunteering and to abstain from sexual intercourse and marijuana use. The sample consisted of 419 late adolescents recruited from across the country through an online survey panel. Participants completed online measures of motivations to engage in donating and volunteering, motivations to abstain from sex and marijuana, and single-item indexes of the four behaviors. Variable-centered analyses (correlation and regression) found evidence for a general motivational factor, motivational specificity by behavioral domain (positive and negative behaviors), motivational specificity by particular behavior (charitable donating, volunteering, sexual risk-taking, and marijuana use), and a stronger relative role for autonomous motivations than controlled motivations. Person-centered analyses (cluster analysis) found four motivation profiles (low motivation, medium motivation, high motivation, and mixed motivation) for all four behaviors and suggested that level of autonomous motivation was a key factor differentiating the groups on levels of behavior. The findings suggest different levels of motivational specificity and highlight the importance of autonomous motivations in predicting behaviors as compared to controlled motivations. Further, similar patterns were found for motivations to engage and to abstain. PMID- 25130714 TI - [Thrombosed orbital varix presenting as a subretinal mass]. PMID- 25130715 TI - Cognitive and neuroprotective effects of chlorogenic acid. AB - OBJECTIVES: The aim of this review was to provide an overview of studies conducted to determine the effects of chlorogenic acid (CGA) on cognition and neurological health. METHODS: A literature search was conducted using PubMed and various search terms including chlorogenic acid, CGA, memory, neuroscience, cognition, nutrition, antioxidant, pharmacokinetics, neuroprotection, and neurodegeneration. RESULTS: Many studies have linked CGA consumption to a wide range of health benefits, including neuroprotection, cardioprotection, weight loss, chemopreventive properties, anti-inflammatory activity, decreased blood pressure, decreased diet-induced insulin resistance, decreased blood pressure, anxiolytic effects, and antihyperalgesic effects. Pre-clinical and clinical studies both provide evidence that CGA supplementation could protect against neurological degeneration and the resulting diseases associated with oxidative stress in the brain; however, no formal, well-controlled studies have been performed to date. DISCUSSION: Recent research suggests that dietary consumption of CGA could produce a wide range of health benefits and physiological effects. There is also mounting evidence that the consumption of polyphenols, including CGA, in the diet could reduce the risk of developing neurodegenerative conditions. Further studies should be conducted with a focus on the effects of CGA on cognition and the nervous system and employing well-designed clinical studies. PMID- 25130716 TI - Genetic, molecular and physiological mechanisms involved in human obesity: Society for Endocrinology Medal Lecture 2012. AB - The health consequences of obesity represent one of the major public health challenges of our time. Whilst the role of environmental drivers such as reduced physical activity and increased food intake is widely acknowledged, the importance of biological factors which influence individual variation in weight is less readily recognised. Considerable evidence suggests that genetic factors influence a person's weight in a given environment and that these genetic influences are more potent at the extremes of the body mass index (BMI) distribution. The discovery that genetic disruption of certain pathways can lead to severe obesity has informed our current understanding of how body weight is regulated by brain circuits that regulate appetite and energy expenditure. These studies provide a framework for investigating patients and ultimately may guide the development of more rational-targeted therapies for genetically susceptible individuals with severe obesity. PMID- 25130717 TI - Stone/tissue differentiation during intracorporeal lithotripsy using diffuse white light reflectance spectroscopy: In vitro and clinical measurements. AB - BACKGROUND AND OBJECTIVE: Holmium laser lithotripsy is the 'gold standard' for intracorporeal fragmentation of stones. However, there is a risk of damaging and perforating the ureter wall when the laser is accidentally fired while the fiber is in contact with tissue. The aim of this study was to evaluate if white illumination light, diffusely reflected back into the treatment fiber and spectrally analyzed, can be used for differentiating between stone and tissue. STUDY DESIGN/MATERIALS AND METHODS: Firstly, in vitro reflectance spectra (Xenon light source, wavelength range lambda = 350-850 nm) of 38 human kidney stones, porcine renal calix and ureter tissue were collected. Secondly, in an in vivo study with 8 patients, 72 ureter and 49 stone reflectance signals were recorded during endourological interventions. The spectra were analyzed to discriminate between stone and tissue by the absence or presence of minima due to hemoglobin absorption at lambda1 = 542nm and lambda3 = 576nm. RESULTS: In vitro, all stone and tissue signals could correctly be identified by calculating the ratio R = I (lambda1 = 542 nm)/I (lambda2 = 475 nm): Because of the hemoglobin absorption at lambda1 , R is smaller for tissue than for calculi. In vivo, only 75% tissue spots could correctly be identified utilizing this method. Using the more sophisticated evaluation of looking for minima in the diffuse reflectance spectra at lambda1 = 542 nm and lambda3 = 576 nm, 62 out of 64 tissue spots were correctly identified (sensitivity 96.9%). This was also the case for 39 out of 43 stone spots. Taking into account the number of measured spectra, a tissue detection probability of 91% and a stone detection probability of 77% was achieved (significance level 5%). CONCLUSION: White light diffusely reflected off the treatment zone into the fiber can be used to strongly improve the safety of Holmium laser lithotripsy by implementing an automatic feedback control algorithm that averts mispositioning the fiber. PMID- 25130718 TI - Family history of psychosis and social, occupational and global outcome in schizophrenia: a meta-analysis. AB - OBJECTIVE: We aimed to investigate associations between family history of psychosis and long-term occupational, social and global (i.e. combined occupational, social and clinical) outcome in schizophrenia. METHOD: A systematic search to identify potentially relevant studies was conducted using seven electronic databases and a manual search of literature. Only observational studies with a follow-up period of at least 2 years were included. RESULTS: The search identified 4081 unique potentially relevant articles, of which 14 met our inclusion criteria. The presence of family history of psychosis was associated with poor occupational and global outcome (n=3; r=0.17; P=0.008, n=11; r=0.13; P=0.002, respectively). CONCLUSION: This was the first systematic review on the effects of family history of psychosis on occupational and social outcome in schizophrenia. Based on the review, the presence of family history of psychosis has a relatively small but statistically significant association with long-term occupational and global outcome in patients with schizophrenia. PMID- 25130719 TI - How French paediatric emergency departments manage painful vaso-occlusive episodes in sickle cell disease patients. AB - AIM: The most common manifestation of sickle cell disease (SCD) is painful vaso occlusive episodes (PVOE), and inappropriate treatment leads to unnecessary suffering and potentially fatal complications. This study describes how French paediatric emergency departments (EDs) manage PVOE and their knowledge, and implementation of the French National Authority for Health recommendations on the management of sickle cell patients. METHODS: A questionnaire on managing PVOE was sent to all the 111 French paediatric EDs. RESULTS: We received responses from 81 (72.9%) of the EDs. Of those who responded to each individual question, 85% said that they had read the national recommendations, 71.6% said they used nalbuphine for moderate PVOE, and 85% used intravenous morphine for severe PVOE. The majority (91.7%) of EDs thought that intravenous morphine provided relief for severe PVOE, but only 30.9% thought that intravenous nalbuphine did. A 50:50 nitrous oxide/oxygen mix was used by 71.3% of departments to relieve procedural pain and by 48% to enhance analgesia when morphine was insufficient for severe pain. CONCLUSIONS: Most French EDs follow the national recommendations for PVOE. Nalbuphine was the most commonly used opioid for moderate PVOE and morphine for severe PVOE. A nitrous oxide/oxygen mixture was widely used for PVOE. PMID- 25130720 TI - Canalicular network morphology is the major determinant of the spatial distribution of mass density in human bone tissue: evidence by means of synchrotron radiation phase-contrast nano-CT. AB - In bone remodeling, maturation of the newly formed osteonal tissue is associated with a rapid primary increase followed by a slower secondary increase of mineralization. This requires supply and precipitation of mineral into the bone matrix. Mineral delivery can occur only from the extracellular fluid via interfaces such as the Haversian system and the osteocyte pore network. We hypothesized that in mineralization, mineral exchange is achieved by the diffusion of mineral from the lacunar-canalicular network (LCN) to the bone matrix, resulting in a gradual change in tissue mineralization with respect to the distance from the pore-matrix interface. We expected to observe alterations in the mass density distribution with tissue age. We further hypothesized that mineral exchange occurs not only at the lacunar but also at the canalicular boundaries. The aim of this study was, therefore, to investigate the spatial distribution of mass density in the perilacunar and pericanalicular bone matrix and to explore how these densities are influenced by tissue aging. This is achieved by analyzing human jawbone specimens originating from four healthy donors and four treated with high-dosage bisphosphonate using synchrotron radiation phase-contrast nano-CT with a 50-nm voxel size. Our results provide the first experimental evidence that mass density in the direct vicinity of both lacunae (p < 0.001) and canaliculi (p < 0.001) is different from the mean matrix mass density, resulting in gradients with respect to the distance from both pore matrix interfaces, which diminish with increasing tissue age. Though limited by the sample size, these findings support our hypotheses. Moreover, the density gradients are more pronounced around the lacunae than around the canaliculi, which are explained by geometrical considerations in the LCN morphology. In addition, we speculate that mineral exchange occurs at all interfaces of the LCN, not only in mineralization but also in mineral homeostasis. PMID- 25130721 TI - RhoA/ROCK pathway mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain. AB - Recent studies have indicated an important role of ATP receptors in spinal microglia, such as P2Y12 or P2Y13, in the development of chronic pain. However, intracellular signaling cascade of these receptors have not been clearly elucidated. We found that intrathecal injection of 2-(methylthio)adenosine 5' diphosphate (2Me-SADP) induced mechanical hypersensitivity and p38 mitogen activated protein kinase (MAPK) phosphorylation in the spinal cord. Intrathecal administration of P2Y12/P2Y13 antagonists and Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor H1152 suppressed not only p38 MAPK phosphorylation, but also mechanical hypersensitivity induced by 2Me-SADP. In the rat peripheral nerve injury model, intrathecal administration of antagonists for the P2Y12/P2Y13 receptor suppressed activation of p38 MAPK in the spinal cord. In addition, subarachnoidal injection of H1152 also attenuated nerve injury-induced spinal p38 MAPK phosphorylation and neuropathic pain behavior, suggesting an essential role of ROCK in nerve injury-induced p38 MAPK activation. We also found that the antagonists of the P2Y12/P2Y13 receptor and H1152 had inhibitory effects on the morphological changes of microglia such as retraction of processes in both 2Me-SADP and nerve injured rats. In contrast these treatments had no effect on the number of Iba1-positive cells in the nerve injury model. Collectively, our results have demonstrated roles of ROCK in the spinal microglia that is involved in p38 MAPK activation and the morphological changes. Inhibition of ROCK signaling may offer a novel target for the development of a neuropathic pain treatment. PMID- 25130722 TI - Transcriptional regulation of CCL20 expression. AB - Chemokines are key mediators of leukocyte recruitment during immunoregulatory and proinflammatory responses. CCL20 is a cysteine-cysteine chemokine that was originally shown to be chemotactic for immature dendritic cells, effector or memory CD4(+) T lymphocytes, and B lymphocytes. Additionally, CCL20 and its only receptor (CCR6) are exploited by cancer cells for migration and metastatic spread and play important roles in the development and progression of cancer. However, it still remains unclear how the activity of the CCL20/CCR6 axis is controlled and regulated at the transcriptional level. The CCL20 promoter region contains a transcription start site, a nuclear factor (NF)-kappaB binding site, a CCAAT/enhancer-binding proteins binding site, an activator protein-1 binding sites, and a specificity protein 1 (Sp1)-binding site. In this review, we outline recent advances in our understanding of the structure of the CCL20 promoter region and discuss the transcriptional regulation of the CCL20 promoter. PMID- 25130723 TI - Genetic battle between Helicobacter pylori and humans. The mechanism underlying homologous recombination in bacteria, which can infect human cells. AB - Helicobacter pylori is a gram-negative pathogenic bacterium that colonises the human stomach. The chronic infection it causes results in peptic ulcers and gastric cancers. H. pylori can easily establish a chronic infection even if the immune system attacks this pathogen with oxidative stress agents and immunoglobulins. This is attributed to bacterial defence mechanisms against these stresses. As a defence mechanism against oxidative stresses, in bacterial genomes, homologous recombination can act as a repair pathway of DNA's double strand breaks (DSBs). Moreover, homologous recombination is also involved in the antigenic variation in H. pylori. Gene conversion alters genomic structures of babA and babB (encoding outer membrane proteins), resulting in escape from immunoglobulin attacks. Thus, homologous recombination in bacteria plays an important role in the maintenance of a chronic infection. In addition, H. pylori infection causes DSBs in human cells. Homologous recombination is also involved in the repair of DSBs in human cells. In this review, we describe the roles of homologous recombination with an emphasis on the maintenance of a chronic infection. PMID- 25130724 TI - Giving blood donors something to drink before donation can prevent fainting symptoms: is there a physiological or psychological reason? AB - The vasovagal reaction has been widely studied but its anatomic and physiological nature remains uncertain. The mechanisms underlying vasovagal reaction related to blood donation are not completely understood either. Does its occurrence depend on the blood donors' physical characteristics and health variables or psychological factors? On the basis that a psychological approach considerably prevents donor reactions, the effect of fruit juice ingestion was studied in a group of 1849 first-time high-school students as a simple strategy to avoid systemic reactions at blood donation. The reasons for the psychological effect of this hydration protocol are stressed also in light of previous physiological studies on the hemodynamic effects of water or carbohydrate drinks. PMID- 25130725 TI - Comparison of plasma exchange performances between Spectra Optia and COBE Spectra apheresis systems in repeated procedures considering variability and using specific statistical models. AB - Repeated therapeutic plasma exchange (TPE) procedures using centrifugation techniques became a standard therapy in some diseases. As the new device Spectra Optia (SPO; Terumo BCT) was available, we studied its performances in repeated procedures in 20 patients in three apheresis units. First we analysed the performance results obtained by SPO. Second we compared the performances of the SPO device to a standard device, COBE Spectra (CSP; Terumo BCT) in the same patients using statistical method of mixed effects linear regression that considers variability between patients, centres and apheresis procedures. The performances analysed were classified according to plasma removal performances and their consequences on patients whose blood disturbances were assessed. Primary outcome was plasma removal efficiency (PRE) and PRE-anticoagulant corrected which was a more accurate parameter. Secondary outcomes corresponded to the volume of ACD-A consumed, platelets content in waste bag, procedure duration and status of coagulation system observed after TPE sessions. Before comparing the performances of both devices we compared the plasma volumes (PVs) processed in both techniques which showed that the PVs processed in SPO procedures were lower than in CSP procedures. In these conditions the statistical analysis revealed similar performances in both apheresis devices in PRE (p = ns) but better performances with SPO when considering higher PRE corrected by anticoagulant volume used (p < 0.05). Comparison of secondary outcomes showed no difference after SPO and CSP. After verifying that pre-apheresis patients' coagulation blood levels were identical before SPO and CSP, we showed identical haemostasis disturbances after SPO and CSP but lower platelet losses and higher fibrinogen post-apheresis blood levels after SPO (p < 0.05). No side effects or technical complications occurred during and after SPO and CSP. This study demonstrated that the Spectra Optia device is an alternative device to today's standard, the COBE Spectra device. PMID- 25130726 TI - Absolute immature platelet count helps differentiate thrombotic thrombocytopenic purpura from hypertension-induced thrombotic microangiopathy. AB - ADAMTS13 activity measurement is used in the diagnostic algorithm of thrombotic thrombocytopenic purpura (TTP), but results may not be available before initiation of therapeutic plasma exchange (TPE). The immature platelet fraction (%-IPF) and the calculated absolute immature platelet count (A-IPC) represent a test of real-time thrombopoiesis, and can be performed in most laboratories using automated analyzers. Here we report on using A-IPC kinetics to exclude idiopathic TTP in a patient with severe hypertension, thrombocytopenia, and acute renal failure, which was confirmed by a normal ADAMTS13. The complete resolution of thrombocytopenia occurred once blood pressure was controlled favoring a diagnosis of hypertension-induced thrombotic microangiopathy. PMID- 25130727 TI - The effects of anakinra on focal cerebral ischemic injury in rats. PMID- 25130728 TI - Enzymes for ecdysteroid biosynthesis: their biological functions in insects and beyond. AB - Steroid hormones are responsible for the coordinated regulation of many aspects of biological processes in multicellular organisms. Since the last century, many studies have identified and characterized steroidogenic enzymes in vertebrates, including mammals. However, much less is known about invertebrate steroidogenic enzymes. In the last 15 years, a number of steroidogenic enzymes and their functions have been characterized in ecdysozoan animals, especially in the fruit fly Drosophila melanogaster. In this review, we summarize the latest knowledge of enzymes crucial for synthesizing ecdysteroids, the principal insect steroid hormones. We also discuss the functional conservation and diversity of ecdysteroidogenic enzymes in other insects and even non-insect species, such as nematodes, vertebrates, and lower eukaryotes. PMID- 25130729 TI - Conformation-specific antibodies to target amyloid beta oligomers and their application to immunotherapy for Alzheimer's disease. AB - Amyloid beta-protein (Abeta) oligomers, intermediates of Abeta aggregation, cause cognitive impairment and synaptotoxicity in the pathogenesis of Alzheimer's disease (AD). Immunotherapy using anti-Abeta antibody is one of the most promising approaches for AD treatment. However, most clinical trials using conventional sequence-specific antibodies have proceeded with difficulty. This is probably due to the unintended removal of the non-pathological monomer and fibrils of Abeta as well as the pathological oligomers by these antibodies that recognize Abeta sequence, which is not involved in synaptotoxicity. Several efforts have been made recently to develop conformation-specific antibodies that target the tertiary structure of Abeta oligomers. Here, we review the recent findings of Abeta oligomers and anti-Abeta antibodies including our own, and discuss their potential as therapeutic and diagnostic tools. PMID- 25130730 TI - Simultaneous measurement of nicotinamide and its catabolites, nicotinamide N oxide, N(1)-methyl-2-pyridone-5-carboxamide, and N(1)-methyl-4-pyridone-3 carboxamide, in mice urine. AB - Nicotinamide N-oxide is a major nicotinamide catabolite in mice but not in humans and rats. A high-performance liquid chromatographic method for the simultaneous measurement of nicotinamide, nicotinamide N-oxide, N(1)-methyl-2-pyridone-5 carboxamide, and N(1)-methyl-4-pyridone-3-carboxamide in mice urine was developed by modifying the mobile phase of a reported method for measurement of nicotinamide N-oxide. PMID- 25130731 TI - cDNA cloning and characterization of vanadium-dependent bromoperoxidases from the red alga Laurencia nipponica. AB - The marine red alga genus Laurencia is one of the richest producers of unique brominated compounds in the marine environment. The cDNAs for two Laurencia nipponica vanadium-dependent bromoperoxidases (LnVBPO1 and LnVBPO2) were cloned and expressed in Escherichia coli. Enzyme assays of recombinant LnVBPO1 and LnVBPO2 using monochlorodimedone revealed that they were thermolabile but their Km values for Br(-) were significantly lower than other red algal VBPOs. The bromination reaction was also assessed using laurediol, the predicted natural precursor of the brominated ether laurencin. Laurediol, protected by trimethylsilyl at the enyne, was converted to deacetyllaurencin by the LnVBPOs, which was confirmed by tandem mass spectrometry. Native LnVBPO partially purified from algal bodies was active, suggesting that LnVBPO is functional in vivo. These results contributed to our knowledge of the biosynthesis of Laurencia brominated metabolites. PMID- 25130732 TI - (2-Nitroethyl)benzene: a major flower scent from the Japanese loquat Eriobotrya japonica [Rosales: Rosaceae]. AB - (2-Nitroethyl)benzene was identified as a major component of the flower scent of the Japanese loquat Eriobotrya japonica [Rosales: Rosaceae], together with p methoxybenzaldehyde and methyl p-methoxybenzoate. The corresponding volatiles from chopped leaves did not contain these three compounds. This is the first time that 1-nitro-2-phenyl-ethane has been demonstrated to be a natural product among Japanese plants, although two Japanese millipedes are known to possess the same aromatics. PMID- 25130733 TI - Total synthesis of aurachins C, D, and L, and a structurally simplified analog of aurachin C. AB - The quinoline antibiotics aurachins C, D, and L, and a structurally simplified analog of aurachin C were synthesized from 1-(2-nitrophenyl)butane-1,3-dione via reductive cyclizations of delta-nitro ketone intermediates, with zinc or iron as key steps. The results of antimicrobial tests indicate that the N hydroxyquinolone nucleus mimics the electron carrier in the respiratory chain more strongly than the quinoline N-oxide nucleus. PMID- 25130734 TI - Diversity in mRNA expression of the serine-type carboxypeptidase ocpG in Aspergillus oryzae through intron retention. AB - Alternative splicing is thought to be a means for diversification of products by mRNA modification. Although some intron retentions are predicted by transcriptome analysis in Aspergillus oryzae, its physiological significance remains unknown. We found that intron retention occurred occasionally in the serine-type carboxypeptidase gene, ocpG. Analysis under various culture conditions revealed that extracellular nitrogen conditions influence splicing patterns; this suggested that there might be a correlation between splicing efficiency and the necessity of OcpG activity for obtaining a nitrogen source. Since further analysis showed that splicing occurred independently in each intron, we constructed ocpG intron-exchanging strain by interchanging the positions of intron-1 and intron-2. The splicing pattern indicated the probability that ocpG intron retention was affected by the secondary structures of intronic mRNA. PMID- 25130736 TI - A genomic search approach to identify carbonyl reductases in Gluconobacter oxydans for enantioselective reduction of ketones. AB - The versatile carbonyl reductases from Gluconobacter oxydans in the enantioselective reduction of ketones to the corresponding alcohols were exploited by genome search approach. All purified enzymes showed activities toward the tested ketoesters with different activities. In the reduction of 4 phenyl-2-butanone with in situ NAD(P)H regeneration system, (S)-alcohol was obtained with an e.e. of up to 100% catalyzed by Gox0644. Under the same experimental condition, all enzymes catalyzed ethyl 4-chloroacetoacetate to give chiral products with an excellent e.e. of up to 99%, except Gox0644. Gox2036 had a strict requirement for NADH as the cofactor and showed excellent enantiospecificity in the synthesis of ethyl (R)-4-chloro-3-hydroxybutanoate. For the reduction of ethyl 2-oxo-4-phenylbutyrate, excellent e.e. (>99%) and high conversion (93.1%) were obtained by Gox0525, whereas the other enzymes showed relatively lower e.e. and conversions. Among them, Gox2036 and Gox0525 showed potentials in the synthesis of chiral alcohols as useful biocatalysts. PMID- 25130735 TI - A genome-wide survey of homeodomain-leucine zipper genes and analysis of cold responsive HD-Zip I members' expression in tomato. AB - Homeodomain-leucine zipper (HD-Zip) proteins are a kind of transcriptional factors that play a vital role in plant growth and development. However, no detailed information of HD-Zip family in tomato has been reported till now. In this study, 51 HD-Zip genes (SlHZ01-51) in this family were identified and categorized into 4 classes by exon-intron and protein structure in tomato (Solanum lycopersicum) genome. The synthetical phylogenetic tree of tomato, Arabidopsis and rice HD-Zip genes were established for an insight into their evolutionary relationships and putative functions. The results showed that the contribution of segmental duplication was larger than that of tandem duplication for expansion and evolution of genes in this family of tomato. The expression profile results under abiotic stress suggested that all SlHZ I genes were responsive to cold stress. This study will provide a clue for the further investigation of functional identification and the role of tomato HD-Zip I subfamily in plant cold stress responses and developmental events. PMID- 25130737 TI - IkappaB kinase epsilon expression in adipocytes is upregulated by interaction with macrophages. AB - Macrophage infiltration in the adipose tissue, and the interaction with adipocytes, is well documented to be involved in fat inflammation and obesity associated complications. In this study, we isolated IkappaB kinase epsilon (IKKepsilon) as a key adipocyte factor that is potentially affected by interaction with macrophages in adipose tissue in vivo. We showed that IKKepsilon mRNA expression levels in white adipose tissue were increased in both genetic and diet-induced obese mouse. Furthermore, IKKepsilon mRNA expression was decreased by the administration of vitamin B6, an anti-inflammatory vitamin, and that IKKepsilon expression levels in adipose tissue were closely correlated with the numbers of infiltrating macrophages. In a co-culture system, we showed that IKKepsilon expression in adipocytes was upregulated by interaction with activated macrophages. This study provides novel insight into IKKepsilon, which is involved in adipose tissue inflammation during the development of obesity. PMID- 25130738 TI - Down-regulated miR-15a mediates the epithelial-mesenchymal transition in renal tubular epithelial cells promoted by high glucose. AB - High glucose (HG) has been reported to be associated with renal dysfunction. And one potential mechanism underlining the dysfunction is the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Present study showed that EMT was induced in the HG-treated renal tubular epithelial cells by promoting the expression of mesenchymal phenotype molecules, such as alpha-SMA and collagen I, and down-regulating the expression of epithelial phenotype molecule E-cadherin. Moreover, we have identified the down-regulation of miR-15a which was accompanied with the HG-induced EMT. And the miR-15a overexpression inhibited the alpha-SMA, collagen I expression, and the promotion of E-cadherin expression by targeting and down-regulating AP4 which was also significantly promoted by the HG in the renal tubular epithelial cells. Thus, this study revealed that the weakening regulation on the AP4 expression by miR-15a might contribute to the HG-induced EMT in the renal tubular epithelial cells. PMID- 25130740 TI - Glutathione contributes to the efflux of selenium from hepatoma cells. AB - Selenite is a selenium source for selenoprotein biosynthesis in mammalian cells. Although previous studies have suggested the involvement of glutathione (GSH) and/or thioredoxin reductase in selenite metabolism, intracellular selenite metabolism remains largely unknown. Here, we report that GSH depletion did not affect the amount of selenoprotein in Hepa 1-6 cells, suggesting that GSH does not play a central role in the reduction of selenite in selenoprotein biosynthesis. On the other hand, we found that GSH is involved in the efflux of low-molecular-weight selenium compounds from cells, presumably via the formation of selenodiglutathione. Moreover, selenite inhibited the efflux of a fluorescent bimane-GS conjugate that is mediated by ATP-dependent multidrug-resistant proteins, implying the existence of an active transporter for selenodiglutathione. This is the first report demonstrating that GSH plays a role in selenium excretion from cells by forming a GSH-conjugate, which may contribute to the distribution, detoxification, and homeostasis of selenium in the body. PMID- 25130741 TI - Regio- and stereoselective oxygenation of proline derivatives by using microbial 2-oxoglutarate-dependent dioxygenases. AB - We evaluated the substrate specificities of four proline cis-selective hydroxylases toward the efficient synthesis of proline derivatives. In an initial evaluation, 15 proline-related compounds were investigated as substrates. In addition to l-proline and l-pipecolinic acid, we found that 3,4-dehydro-l proline, l-azetidine-2-carboxylic acid, cis-3-hydroxy-l-proline, and l thioproline were also oxygenated. Subsequently, the product structures were determined, revealing cis-3,4-epoxy-l-proline, cis-3-hydroxy-l-azetidine-2 carboxylic acid, and 2,3-cis-3,4-cis-3,4-dihydroxy-l-proline. PMID- 25130739 TI - Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAP kinase activity. AB - Bisphenol A (BPA) is considered to be an endocrine disruptor, but the mechanisms by which it disrupts endocrine functions are poorly understood. Here, we have shown that BPA binds both estrogen receptor (ER)-alpha and ER-beta (ER-beta) using a fluorescence polarization competitive binding assay. In addition, we found that BPA induced cell proliferation by modulating cell cycle-related genes in the MCF-7 human mammary cancer cell line. Moreover, using a BG1 luciferase ER transactivation assay, we found that BPA has estrogenic activity. Modulating the MAPK pathway by using an ERK inhibitor (PD98059) or a JNK inhibitor (SP600125) had no effect on the ability of BPA to induce estrogenic activity. However, the antiestrogen, ICI 182,780, and the p38 inhibitor, PD 169316 successfully blocked BPA-induced estrogenic activity. Our findings suggest that BPA mimics ER dependent estrogenic activity by targeting proteins that regulate the cell cycle and p38 MAPK. PMID- 25130742 TI - Ethanol stress impairs protein folding in the endoplasmic reticulum and activates Ire1 in Saccharomyces cerevisiae. AB - Impaired protein folding in the endoplasmic reticulum (ER) evokes the unfolded protein response (UPR), which is triggered in budding yeast, Saccharomyces cerevisiae, by the ER-located transmembrane protein Ire1. Here, we report that ethanol stress damages protein folding in the ER, causing activation of Ire1 in yeast cells. The UPR likely contributes to the ethanol tolerance of yeast cells. PMID- 25130743 TI - Anti-diabetic properties of Daphniphyllum macropodum fruit and its active compound. AB - We evaluated in vitro anti-diabetic activities of 497 native plants of Jeju Island (South Korea) by measuring the induction of adipocyte differentiation. Among the plants, Daphniphyllum macropodum fruit extract (DME) had the highest peroxisome proliferator-activated receptor gamma (PPARgamma) agonist activity and was therefore selected as a potential source of anti-diabetic agents. To elucidate the active components of DME, constituent compounds were purified and their effects on the adipocyte differentiation were studied. Using activity guided fractionation, four compounds were isolated from DME and their adipogenic effects were evaluated. Among the compounds isolated, 5,7-dihydroxychromone potently induced the differentiation of mouse 3T3-L1 preadipocytes. DME and 5,7 dihydroxychromone increased PPARgamma and liver X receptor alpha (LXRalpha) mRNA expression levels. To determine whether the adipogenic effects we observed might affect serum glucose levels, we undertook in vivo experiment using streptozotocin /high-fat diet-induced type 2 diabetes mouse model. DME supplementation reduced serum glucose, total cholesterol, and triacylglycerol levels in diabetes mice. These results suggest that DME may be useful for the prevention and treatment of type 2 diabetes mellitus. Moreover, it was proposed that 5,7-dihydroxychromone isolated from DME is one of the active compounds that may contribute to regulate blood glucose levels. PMID- 25130744 TI - Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression. AB - Rubus coreanus Miquel (RCM) is used to promote prostate health and has been shown to have anti-oxidant and anti-carcinogenic activities. However, the effects and mechanisms of RCM on prostate cancer metastasis remain unclear. PC-3 and DU 145 cells were treated with ethanol or water extract of unripe or ripe RCM and examined for cell invasion, migration, and matrix metalloproteinases (MMPs) activity and expression. Phosphoinositide 3-kinase (PI3K) and Akt activities were examined. Unripe RCM extracts exerted significant inhibitory effects on cell migration, invasion, and MMPs activities. A significant reduction in MMPs activities by unripe RCM ethanol extract treatment (UE) was associated with reduction of MMPs expression and induction of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, PI3K/Akt activity was diminished by UE treatment. In this study, we demonstrated that UE decreased metastatic potential of prostate cancer cells by reducing MMPs expression through the suppression of PI3K/Akt phosphorylation, thereby decreasing MMP activity and enhancing TIMPs expression. PMID- 25130745 TI - Effects of drying conditions on moisture distribution in rehydrated spaghetti. AB - Moisture distributions in spaghettis prepared at a maximum temperature of 50, 70, or 85 degrees C, designated as LT-, HT-, or VHT-spaghetti, respectively, and cooked to the average moisture content of 1.71 +/- 0.01 kg-H2O/kg-d.m., were measured. The moisture contents near the surface and at the center of the LT spaghetti were lower and higher, respectively, than those of HT- and VHT spaghetti. PMID- 25130747 TI - Diallyl trisulfide induces apoptosis in Jurkat cells by the modification of cysteine residues in thioredoxin. AB - We reported the regulation of protein function by oxidative modification of the specific cysteine residue(s) by diallyl trisulfide (DATS). In this study, we examined if DATS modifies the cysteine residue of thioredoxin (Trx) by urea polyacryl amide gel electrophoresis. DATS modified two specific cysteine residues in Trx and this oxidative modification of cysteine residues would be sole causative of the apoptosis induced by DATS in leukemic cells. PMID- 25130748 TI - Optimization of culture conditions of Fusarium solani for the production of neoN methylsansalvamide. AB - The aim of this study was to optimize the culture conditions of Fusarium solani KCCM90040 on cereal grain for the production of neoN-methylsansalvamide, a novel low-molecular-weight cyclic pentadepsipeptide exhibiting cytotoxic and multidrug resistance reversal effects. From the analysis of variance results using response surface methodology, temperature, initial moisture content, and growth time were shown to be important parameters for the production of neoN-methylsansalvamide on cereal grain. A model was established in the present study to describe the relationship between environmental conditions and the production of neoN methylsansalvamide on rice, the selected cereal grain. The optimal culture conditions were determined at 25.79 degrees C with the initial moisture content of 40.79%, and 16.19 days of growth time. This report will give important information concerning the optimization of environmental conditions using statistic methodology for the production of a new cyclic pentadepsipeptide from fungi. PMID- 25130746 TI - Identification of molecular target of diallyl trisulfide in leukemic cells. AB - To identify the molecular target of diallyl trisulfide (DATS) in human leukemic cell line U937, we examined modification of thiol group(s) of cellular proteins by the redox 2D PAGE. A unique protein spot appeared by DATS treatment was identified to be heat shock protein 27 (HSP27). Hsp27 is suggested to be one of the molecular target of DATS in U937. PMID- 25130749 TI - A cell wall protein (YqgA) is genetically related to the cell wall-degrading dl endopeptidases in Bacillus subtilis. AB - The Gram-positive bacterium Bacillus subtilis has a thick cell wall. The cell wall contains various proteins, both for secretion and for peptidoglycan (PG) maintenance. Penicillin-binding proteins for PG synthesis, PG hydrolases (autolysins), and regulator proteins for the autolysins are the known components of the PG maintenance system. YqgA was identified as an abundant protein attached to the cell wall of B. subtilis through a proteomics analysis. The YqgA protein was localized at cell division sites during the transition period between the exponential and the stationary phases. YqgA localization was affected by mutations in the dl-endopeptidases (DLEPases), which are the autolysins involved in cell morphogenesis. Furthermore, yqgA mutations on a background of defective DLEPases led to delays in cell growth and cell morphological changes. These results demonstrate that yqgA is genetically related to the genes encoding DLEPases involved in cell morphogenesis. PMID- 25130750 TI - Comparison of hydrophilic variation and bioethanol production of furfural residues after delignification pretreatment. AB - Furfural residue (FR) is a waste lignocellulosic material with enormous potential for bioethanol production. In this study, bioethanol production from FR after delignification was compared. Hydrophilic variation was measured by conductometric titration to detect the relationship between hydrophilicity and bioethanol production. It was found that ethanol yield increased as delignification enhanced, and it reached up to 75.6% of theoretical yield for samples with 8.7% lignin. The amount of by-products decreased as delignification increased. New inflection points appeared in conductometric titration curves of samples that were partially delignified, but they vanished in the curves of the highly delignified samples. Total charges and carboxyl levels increased after slight delignification, and they decreased upon further delignification. These phenomena suggested some new hydrophilic groups were formed during pretreated delignification, which would be beneficial to enzymatic hydrolysis. However, some newly formed groups may act as toxicant to the yeast during simultaneous saccharification and fermentation. PMID- 25130751 TI - Evaluation of bifidobacterial adhesion to acidic sugar chains of porcine colonic mucins. AB - The aim of this study was to assess the adhesion of Bifidobacterium strains to acidic carbohydrate moieties of porcine colonic mucin. Mucins were extracted and purified via gel filtration chromatography followed by density-gradient ultracentrifugation. The presence of sulfated and sialylated carbohydrates in mucins was shown by enzyme-linked immunosorbent assays using PGM34 and HMC31 monoclonal antibodies (mAbs), respectively. Adhesion of Bifidobacterium strains to mucin preparations was markedly affected by the degree of purification. In eight of 22 strains, we observed increased adhesion to mucin preparations purified by ultracentrifugation. Moreover, in some of these eight strains, adhesion to mucin was reduced by pretreatment with sulfatase and/or sialidase, and competitively inhibited by pretreatment with PGM34 and/or HCM31 mAbs. Our results showed that some Bifidobacterium strains adhered to sulfo- and/or sialomucin and were able to recognize carbohydrate structures of the mAbs epitopes. PMID- 25130752 TI - Antioxidant activities of cysteine derivatives against lipid oxidation in anhydrous media. AB - This study investigated antioxidant activities of cysteine derivatives of amino and carboxylic acid moieties against lipid oxidation in anhydrous acetonitrile. Only cysteine derivatives bearing free amino or carboxylate ion were found to exert potent antioxidant activities. Sequential proton loss and electron transfer like proton shift and subsequent electron transfer (PS-ET) mechanism may facilitate the antioxidant activities of cysteine derivatives against lipid oxidation in anhydrous media. PMID- 25130753 TI - Pattern of visuospatial lateralization in two corvid species, black-billed magpies and Clark's nutcrackers. AB - Cerebral lateralization is widespread amongst vertebrate species suggesting advantages are gained by having one of the brain's hemispheres exert dominant control over certain cognitive functions. A recently devised task for assessing lateralization of visuospatial attention by birds (Diekamp et al., 2005) has allowed researchers to suggest the corpus callosum may not be necessary for the emergence of such asymmetries. More recently, this task has been adopted to examine the embryonic development of lateralization in birds, research which may provide important insights as to the underlying genetic mechanisms (Chiandetti, 2011; Chiandetti et al., 2013) of vertebrate cerebral lateralization. However, to date only chicks and pigeons have been used in this paradigm. Thus, it is unclear whether other avian species will also show lateralization of visuospatial attention during this task. Here, we examined the pattern of visuospatial lateralization in two corvid species: social black-billed magpies (Pica hudsonia) and non-social Clark's nutcrackers (Nucifraga columbiana). We find that neither the magpies nor the nutcrackers show evidence for population level lateralization or predictable individual level lateralization, as only a subset of individuals of each species showed a significant individual bias, which were rarely stable over repeated testing. PMID- 25130754 TI - Influence of temperament score and handling facility on stress, reproductive hormone concentrations, and fixed time AI pregnancy rates in beef heifers. AB - The objectives were (i) to evaluate the effect of temperament, determined by modified 2-point chute exit and gait score, on artificial insemination (AI) pregnancy rates in beef heifers following fixed time AI and (ii) to determine the effect of temperament on cortisol, substance-P, prolactin and progesterone at initiation of synchronization and at the time of AI. Angus beef heifers (n = 967) at eight locations were included in this study. At the initiation of synchronization (Day 0 = initiation of synchronization), all heifers received a body condition score (BCS), and temperament score (0 = calm; slow exit and walk or 1 = excitable; fast exit or jump or trot or run). Blood samples were collected from a sub-population of heifers (n = 86) at both synchronization initiation and the time of AI to determine the differences in serum progesterone, cortisol, prolactin and substance-P concentrations between temperament groups. Heifers were synchronized with 5-day CO-Synch+ controlled internal drug release (CIDR) protocol and were inseminated at 56 h after CIDR removal. Heifers were examined for pregnancy by ultrasound 70 days after AI to determine AI pregnancy. Controlling for synchronization treatment (p = 0.03), facility design (p = 0.05), and cattle handling facility design by temperament score interaction (p = 0.02), the AI pregnancy differed between heifers with excitable and calm temperament (51.9% vs 60.3%; p = 0.01). The alley-way with acute bends and turns, and long straight alley-way had lower AI pregnancy rate than did the semicircular alley way (53.5%, 56.3% and 67.0% respectively; p = 0.05). The serum hormone concentrations differed significantly between different types of cattle handling facility (p < 0.05). The cattle handling facility design by temperament group interactions significantly influenced progesterone (p = 0.01), cortisol (p = 0.01), prolactin (p = 0.02) and substance-P (p = 0.04) both at the initiation of synchronization and at the time of AI. Inter- and intra-rater agreement for temperament scoring were moderate and good (Kappa = 0.596 +/- 0.07 and 0.797 +/- 0.11) respectively. The predictive value for calm and pregnant to AI was 0.87, and excited and non-pregnant to AI was 0.76. In conclusion, the modified 2-point temperament scoring method can be used to identify heifers with excitable temperament. Heifers with excitable temperament had lower AI pregnancy. Further, cattle handling facility design influenced the temperament and AI pregnancy. PMID- 25130755 TI - Cranial nerve VI palsy as an initial presentation of necrotizing sarcoid granulomatosis in a 14-year-old female: case report and literature review. AB - OBJECTIVES: We describe a case of pediatric necrotizing sarcoid granulomatosis (NSG) presenting with right cranial nerve VI palsy and multiple lung nodules, successfully treated with corticosteroids. METHODS: This is a descriptive case report of one patient with review of the literature. RESULTS: A 14-year-old Caucasian female presented with complaints of pain on inspiration and dyspnea on exertion, as well as diplopia that was worse with right gaze. The patient presented to our emergency department with persistent diplopia and was found to have stable right cranial nerve VI palsy. CTA showed multiple pulmonary nodules. Despite continued extensive multispecialty work-up, the patient's cranial nerve VI palsy had not resolved, thus tissue confirmation via lung biopsy was performed. Pathologic diagnosis revealed necrotizing sarcoid granulomatosis. The patient was subsequently started on intravenous corticosteroids, which led to the rapid resolution of her presenting symptoms. CONCLUSIONS: Necrotizing sarcoid granulomatosis is a multisystem organ disease that is rare in children. Pathology commonly reveals epithelioid noncaseating granuloma and granulomatous vasculitis with necrosis. We report an unusual presentation involving sixth nerve palsy in a 14-year-old girl. Diagnosis was determined and confirmed by histopathology of a pulmonary nodule biopsy. This is the first case to our knowledge of NSG presenting with cranial nerve palsy in a pediatric patient. PMID- 25130756 TI - Do hospitalists overuse proton pump inhibitors? Data from a contemporary cohort. PMID- 25130757 TI - Evidence for multiple paternity in the school shark Galeorhinus galeus found in New Zealand waters. AB - This study assessed the levels of relatedness of Galeorhinus galeus of progeny arrays using six microsatellite DNA markers. A parentage analysis from five families (mother and litter) from the North Island of New Zealand suggested the occurrence of genetic polyandry in G. galeus with two of the five litters showing multiple sires involved in the progeny arrays. This finding may be consistent with the reproductive characteristics of G. galeus, in which females can potentially store sperm for long periods of time after the mating season. PMID- 25130758 TI - Metal deposition at the liquid-liquid interface. AB - Metal nanoparticles are readily formed, with a reasonable degree of size and shape control, using solution-based reduction methods under ambient conditions. Despite the large number of reports in this field, much of our knowledge of nanoparticle growth is largely empirical, with the relationship between particle form and growth conditions, for example, still not well understood. Many nanoparticle preparation routes actually depend on not one, but two, solution phases, i.e. the syntheses involve reaction or transfer at the liquid-liquid (organic-water) interface. This interface can be polarised electrochemically, an approach that offers promise as a route to better understanding, and ultimately control, of nanoparticle growth. PMID- 25130759 TI - An Evaluation of Laboratory Efficiency in Shanghai Emergency by Turn Around Times Level. AB - OBJECTIVE: China launched a health care reform policy due to the aging population and rapid urbanization. However, emergency overcrowding is not improved. We assessed the laboratory efficiency of emergency department (ED) in Shanghai hospitals. METHODS: We recorded the turn around times for processing laboratory biomarkers to assess laboratory efficiency at 17 EDs in national/regional hospitals. We compared TAT between national and regional hospitals and between central and ED laboratories to analyze the relationship between the laboratory efficiency and the ED overcrowding. RESULTS: All the participating hospitals have an emergency laboratory. The median TAT for c-TNT was 61 min (46-76 min) at regional EDs compared with 64 min (46-87 min) at national EDs; therefore, the TAT at regional EDs were more efficient (P < 0.05). The TAT were longer (65 min (53 85 min)) at ED labs than (60 min (42-83 min)) at central labs (P < 0.05), independent of the hospital tier and working period. We discovered that only 9% of investigated samples at Tier II EDs and 5% at Tier III EDs were assayed by point-of-care (POC) instruments. CONCLUSION: Our TAT level is approaching the recommended international standard. However, the TAT evaluation from ED laboratories demonstrates that their existence does not decrease the waiting time for laboratory reports compared to central laboratory. Thus, they have not yet approached a level to share the burden of the ED overcrowding. Further arrangement should be assigned to separate the function of emergency laboratory and central laboratory. It is worth deploying the POC assay in the ED, which will save twice the TAT level. The idea of evaluating routine laboratory efficiency by TAT at ED is fast, convenient, although it does not represent the general level of laboratory efficiency. PMID- 25130760 TI - Sleep duration, sleep quality, and obesity risk among older adults from six middle-income countries: findings from the study on global AGEing and adult health (SAGE). AB - OBJECTIVES: Changes in sleep patterns often occur in older adults. Previous studies have documented associations between sleep duration, sleep quality, and obesity risk in older individuals, yet few studies have examined these trends in lower-income countries. The present cross-sectional study uses nationally representative datasets from six countries to examine these relationships. METHODS: Two hypotheses related to obesity risk and sleep patterns were tested using data from the first wave of the World Health Organization's Study on global AGEing and adult health (SAGE). This longitudinal study draws on samples of older adults (>50 years old) in six middle-income countries (China, Ghana, India, Mexico, Russian Federation, and South Africa). Self-report data were used to measure sleep duration, sleep quality, lifestyle and sociodemographic information, while anthropometric measurements were collected to assess body mass index (BMI) and waist circumference (WC). Multiple linear regressions were used to examine the relationship between sleep patterns and obesity risk while controlling for lifestyle factors. RESULTS: Shorter sleep durations in both men and women were significantly associated with higher BMI and WC measures (P < 0.05). Low sleep quality did not significantly contribute to increased obesity risk. Surprisingly, high sleep quality was significantly associated with increased male BMI and WC in China and India (P < 0.01). CONCLUSIONS: This study documented an association between short sleep duration and increased obesity risk, which is important given the global increase of obesity-related diseases. PMID- 25130761 TI - Flexor tendons repair: effect of core sutures caliber with increased number of suture strands and peripheral sutures. A sheep model. AB - BACKGROUND: Surgeons have aimed to achieve strong repair so as to begin early active rehabilitation programs for flexor tendon injury. Multi-strand suture techniques were developed to gain improved gap resistance and ultimate force compared with the respective two-strand techniques. In vivo studies indicate that multiple strands may cause ischemia during the intrinsic healing process by decreasing the total cross-sectional area of the injured site, unless the total cross-sectional area of the sutures is not decreased. HYPOTHESIS: The hypothesis was to design an in vitro study to understand the biomechanical relationship between suture calibers of core sutures with increased number of suture strands and peripheral suture on final repair strength. MATERIALS AND METHODS: Sixty fresh sheep forelimb flexor digitorum profundus tendons were randomly placed into three groups (A, B, and C), each containing 20 specimens, for tendon repair. Two , four-, and eight-strand suture techniques were respectively used in Groups A, B, and C. A simple running peripheral suture technique was used in Subgroups A2, B2, and C2. For each repaired tendon, the 2-mm gap-formation force, 2-mm gap formation strength, maximum breaking force and maximum breaking strength were determined. RESULTS: Differences in 2-mm gap-formation force and 2-mm gap formation strength were found between Subgroups A1 and A2, B1 and B2, and C1 and C2. Between Groups A and B, A and C, and B and C, there was no difference as well. CONCLUSION: Both the number of strands and the ratio between the total suture volume and tendon volume at the repair site are important for ideal repair. If the total cross-sectional area of the sutures is equal in 2-strand, 4 strand, and 8-strand procedure, there is no difference in the strength of the repair. A decrease in caliber size suture requires more passes to achieve the same strength. Instead, it is much better to use peripheral suture techniques to improve the strength of the repair with larger diameter 2-strand core sutures. PMID- 25130762 TI - Stemmed hemiarthroplasty versus resurfacing in primary shoulder osteoarthritis: a single-center retrospective series of 78 patients. AB - INTRODUCTION: Resurfacing shoulder arthroplasty is proposed in primary osteoarthritis of the shoulder. The present study compared resurfacing versus 3rd generation stemmed hemiarthroplasty in terms of survival, functional results and implant positioning effects. MATERIALS AND METHODS: Seventy eight patients underwent arthroplasty for primary osteoarthritis of the shoulder: 41 by resurfacing and 37 by stemmed hemiarthroplasty. The two populations were comparable on all baseline variables. Minimum follow-up was 2 years. The principal assessment criterion was survivorship with surgical revision as end point. Secondary criteria were functional results on Constant, quick-DASH, Neer and SSV scores, and implant positioning effects assessed on radiology. RESULTS: At a mean 44 months' follow-up (range, 24-118 months), there were no significant differences in functional scores. Radiologic analysis found greater varus positioning and lateral offset of the humeral head in resurfacing compared with stemmed hemiarthroplasty (128 degrees vs 138 degrees , P<0.01; 6.5 +/- 2 vs 4.6 +/- 1.6mm, P<0.01). Survivorship without revision was significantly poorer in resurfacing, with 4 revision procedures for glenoid wear (9.8%), versus none in hemiarthroplasty (P=0.02). There was no correlation between humeral head size, positioning or lateral offset and revision. CONCLUSION: Revision-free survival was significantly lower in resurfacing than in hemiarthroplasty. Greater humeral head size may increase lateral offset, accelerating glenoid wear. Down-sizing the humeral head in resurfacing procedures might limit these complications. LEVEL OF EVIDENCE: Level III; case-control study. PMID- 25130763 TI - Does Biolox Delta ceramic reduce the rate of component fractures in total hip replacement? AB - Biolox Delta ceramic has been optimized with nano-sized, yttria-stabilized tetragonal zirconium and strontium oxide to help limit cracking propagation. Although its mechanical properties are better than those of earlier generation ceramics, existing data on this material are limited, thus the goals of this study were to determine: 1) the remaining rate of implant fracture; 2) the ideal combination of head diameter and component position. Hypothesis. We hypothesized that the use of the ceramic composite Biolox Delta had reduced the risk of implant fracture. Materials and methods. The bibliographic search (in Pubmed database with the key words "ceramic fracture" and "total hip prosthesis ") identified 46 articles on fractures in third or fourth generation ceramic components, including 5 involving Biolox Delta. Manufacturer's data and ANSM (Agence nationale de securite du medicament et des produits de sante) (National Agency for Safety of Drugs and Medical Products) reports were compared with the few clinical cases published in the literature. Results. According to the manufacturer (CeramTec GmbH, Plochingen, Germany), the use of Biolox Delta ceramic has reduced the rate of femoral head fractures to 0.003% compared to 0.021% with alumina ceramic. The fracture rate of liners has remained stable, at approximately 0.03%. The number of ANSM reports confirmed these tendencies. The rate of head component fractures decreases as the head diameter increases. The quality of impaction on the morse taper (cleanliness of the taper, insertion along the axis) plays an important role. Although it is generally only available for cup sizes above 50mm, a 36-mm head diameter seems to be optimal because it prevents impingement between the cup rim and the neck of the stem, without increasing micro-separation with larger diameters. Conclusion. Although Biolox Delta ceramic is more resistant to fractures than alumina ceramic, it can be fractured under suboptimal implantation conditions including edge loading. Its use requires the same precautions as other hard-on-hard bearings and requires special attention to cup position, insertion on or in morse tapers and adjustment of leg length. LEVEL OF EVIDENCE: V expert's opinion. PMID- 25130764 TI - Estimating premium sensitivity for children's public health insurance coverage: selection but no death spiral. AB - OBJECTIVE: To estimate the effect of premium increases on the probability that near-poor and moderate-income children disenroll from public coverage. DATA SOURCES: Enrollment, eligibility, and claims data for Georgia's PeachCare for Kids(TM) (CHIP) program for multiple years. STUDY DESIGN: We exploited policy induced variation in premiums generated by cross-sectional differences and changes over time in enrollee age, family size, and income to estimate the duration of enrollment as a function of the effective (per child) premium. We classify children as being of low, medium, or high illness severity. PRINCIPAL FINDINGS: A dollar increase in the per-child premium is associated with a slight increase in a typical child's monthly probability of exiting coverage from 7.70 to 7.83 percent. Children with low illness severity have a significantly higher monthly baseline probability of exiting than children with medium or high illness severity, but the enrollment response to premium increases is similar across all three groups. CONCLUSIONS: Success in achieving coverage gains through public programs is tempered by persistent problems in maintaining enrollment, which is modestly affected by premium increases. Retention is subject to adverse selection problems, but premium increases do not appear to significantly magnify the selection problem in this case. PMID- 25130765 TI - Multidimensional analysis of nanoparticles with highly disperse properties using multiwavelength analytical ultracentrifugation. AB - The worldwide trend in nanoparticle technology toward increasing complexity must be directly linked to more advanced characterization methods of size, shape and related properties, applicable to many different particle systems in science and technology. Available techniques for nanoparticle characterization are predominantly focused on size characterization. However, simultaneous size and shape characterization is still an unresolved major challenge. We demonstrate that analytical ultracentrifugation with a multiwavelength detector is a powerful technique to address multidimensional nanoparticle analysis. Using a high performance optical setup and data acquisition software, information on size, shape anisotropy and optical properties were accessible in one single experiment with unmatched accuracy and resolution. A dynamic rotor speed gradient allowed us to investigate broad distributions on a short time scale and differentiate between gold nanorod species including the precise evaluation of aggregate formation. We report how to distinguish between different species of single-wall carbon nanotubes in just one experiment using the wavelength-dependent sedimentation coefficient distribution without the necessity of time-consuming purification methods. Furthermore, CdTe nanoparticles of different size and optical properties were investigated in a single experiment providing important information on structure-property relations. Thus, multidimensional information on size, density, shape and optical properties of nanoparticulate systems becomes accessible by means of analytical ultracentrifugation equipped with multiwavelength detection. PMID- 25130766 TI - Addressing the shortage of health professionals in South Africa through the development of a new cadre of health worker: the creation of Clinical Associates. AB - South Africa made a decision in 2002 to develop so-called mid-level medical workers, now known as clinical associates. This article describes the background to this decision, and the national process of developing the profession and its scope of practice, which was aligned with the needs of the health service, particularly those of rural district hospitals. A common national curriculum was then developed, with implementation in three faculties. The first graduates have entered the profession, starting in 2011, and are in the process of establishing themselves across the country. They are already making an important contribution to rural health care, and are seeking ways in which the profession can be enhanced to ensure sustainability. The profession needs to adapt itself to the changing realities of the South African context. PMID- 25130767 TI - Sudden death in a 15-year-old with diffuse cardiac rhabdomyomatosis: an autopsy case report. AB - A 15-year-old African-American female with a 4-month history of sporadic rapid heartbeat and fatigue was found pulseless and apneic in her residence. At autopsy, patchy scarring was diffuse throughout the circumference of the left ventricle of the heart. Microscopically, the myocardium had diffuse infiltration of rhabdomyoma-like cells with significant associated fibrosis. Unlike cardiac rhabdomyoma, there was no discrete tumor mass. Differential diagnoses considered were congenital cardiac rhabdomyoma with partial regression, cardiac fibroma, histiocytoid cardiomyopathy, glycogen storage diseases, and drug-induced vacuolar cardiomyopathy. However, the findings are most consistent with cardiac rhabdomyomatosis, an entity not well described in the literature. PMID- 25130769 TI - Relations between virtues and positive mental health in a Korean population: a Multiple Indicators Multiple Causes (MIMIC) model approach. AB - A Multiple Indicators Multiple Causes (MIMIC) approach was applied to investigate the relationship between virtues and positive mental health as determined using the Character Strength Test and the Mental Health Continuum-Short Form. The study participants were 876 college students (54% women; overall mean age [SD] 21.50 years [2.35]) recruited from introductory psychology courses at two universities in Seoul. Findings revealed that the intellectual virtues of college students predicted subjective well-being according to all emotional, social and psychological measures. Results are discussed in the context of previous work using the Values in Action classification of virtues and character strengths. In addition, implications regarding understanding the nature and possible origins of positive mental health are outlined. PMID- 25130768 TI - Comparative study of temporary effect on the water content at different depths of the skin by hot and cold moisturizing formulations. AB - BACKGROUND: Researchers have studied the water content at different skin depths. Since skin differs among tissue depth, we sought to determine the depth variability of the water content after moisturizing formulation application. Furthermore, we compared the effects of formulations with different type of manufacturing processes (hot and cold process). METHODS: To characterize the variations in the water content at different depths in the skin, measurements were done on the center of the inner forearm middle line of 18 sitting healthy women, before and after 1, 3, and 5 h of the application of two different moisturizing formulations (hot and cold process). Measurements included stratum corneum hydration via capacitance (SC) at 1.25 MHz (30-40 MUm), and dermal water via tissue dielectric constant (TDC) at 300 MHz to depths of 500, 1500, and 2500 MUm. RESULTS: There were significant differences between the SC mean values at all evaluated time intervals after application of both formulations when compared to baseline before application (T0). The SC mean values at 1 and 3 h are higher than those of the 5 h post application for both formulations. When comparing the formulations, hot formulation shows higher SC levels at 3 and 5 h, than cold formulation. TDC mean values to skin depths of 500 and 1500 MUm increased after the application for both formulations. This increase was statistically significant at 1 and 3 h, when compared with T0. At 5 h no increases were seen in the TDC for any of the formulations. When comparing the mean values of each time evaluated, there is no statistically significant difference between the two formulations at depth of neither 500 MUm nor 1500 MUm. TDC mean value to a depth of 2500 MUm does not increase after the application of any of the formulations. CONCLUSIONS: Hot and cold formulations are effective moisturizers; however, a distinct profile was obtained for each. When water content averages were compared, the effect of hot formulation in the superficial layers of the skin was greater and longer in time than those of the cold formulation. On the other hand, moisturizing formulations applied to the skin affected the dermis water content until depth of 1500 MUm. PMID- 25130770 TI - Heparin co-factor II enhances cell motility and promotes metastasis in non-small cell lung cancer. AB - Using the Serial Analysis of Gene Expression (SAGE) database from the Cancer Genome Anatomy Project, we identified heparin co-factor II (HCII), which is over expressed in non-small cell lung cancer (NSCLC). Here, we investigated the clinical significance of HCII and provided molecular evidence to support the suggestion that HCII could enhance cancer metastasis in NSCLC. We found that high HCII expression in tumour tissue was associated with increased cancer recurrence and shorter overall survival times in 75 clinically operable NSCLC patients. High pretreatment plasma concentration of HCII was associated with reduced overall survival in 57 consecutive NSCLC patients. We over-expressed and knocked down HCII expression in lung cancer cell lines and confirmed that HCII could promote cell motility, invasion ability and filopodium dynamics in NSCLC cells in vitro and increased metastatic colonization in an in vivo mouse model. Exogenous treatment of HCII promoted cancer cell migration, and this promigratory effect of HCII was independent of thrombin. We further showed that HCII could up-regulate cancer cell migration through the activation of PI3K, which acts upstream of Rac1 and Cdc42, and this effect could be blocked by heparin. We suggest that HCII is a novel metastasis enhancer and may be used as a prognostic predictor for heparin treatment in NSCLC. PMID- 25130772 TI - The crystallization water of gypsum rocks is a relevant water source for plants. AB - Some minerals, like gypsum, hold water in their crystalline structure. Although still unexplored, the use of such crystallization water by organisms would point to a completely new water source for life, critical under dry conditions. Here we use the fact that the isotopic composition of free water differs from gypsum crystallization water to show that plants can use crystallization water from the gypsum structure. The composition of the xylem sap of gypsum plants during summer shows closer values to gypsum crystallization water than to free soil water. Crystallization water represents a significant water source for organisms growing on gypsum, especially during summer, when it accounts for 70-90% of the water used by shallow-rooted plants. Given the widespread occurrence of gypsum in dry lands throughout the Earth and in Mars, these results may have important implications for arid land reclamation and exobiology. PMID- 25130771 TI - Development and application of molecular methods (PCR) for detection of Tasmanian Atlantic salmon reovirus. AB - Molecular (PCR) diagnostic tests for the detection and identification of aquareovirus in general, and Tasmanian Atlantic salmon reovirus (TSRV) specifically, were developed, and their diagnostic sensitivity and specificity were determined and compared with virus isolation in cell culture. Intralaboratory and interlaboratory comparison of PCR (conventional hemi-nested RT-PCR & RT-qPCR) and virus isolation in cell culture using finfish cell lines, CHSE-214 and EPC, was carried out for the detection and identification of TSRV using field samples of farmed Atlantic salmon Salmo salar, L. from various aquaculture sites around Tasmania. The interlaboratory comparison of diagnostic methods was carried out between two laboratories, AAHL-CSIRO and DPIPWE-Tasmania. A total of 144 fish from nine sites (12-33 fish per site) were sampled from two regions of Tasmania (Tamar River estuary in the north and Huon River estuary in the south-east) during late spring to early summer of 2009, and the data were analysed using different statistical approaches. The prevalence of TSRV ranged from 6% to 22% in both regions. All the diagnostic methods (data from both laboratories) had high specificity, while the estimated sensitivity varied between tests with RT-qPCR being the most sensitive (95.2%) method followed by virus isolation and then conventional hemi-nested RT-PCR. PMID- 25130773 TI - Effects of three hydrogen-rich liquids on hemorrhagic shock in rats. AB - BACKGROUND: Hydrogen-rich saline provides a high concentration of hydrogen, which selectively reduces levels of hydroxyl radicals and alleviates acute oxidative stress in many models. We investigated the protective effects and mechanisms of three different hydrogen-rich liquid resuscitation preparations on lung injury induced uncontrolled-hemorrhagic shock (UHS) in rats. MATERIALS AND METHODS: A UHS rat model was prepared using the method of Capone et al. of arterial bleeding and tail amputation. Healthy male Wistar rats were randomly divided into seven groups (10 per group) to receive: sham treatment; Ringer solution; hydrogen-rich Ringer solution (H-Ringer solution); hydroxyethyl starch (HES); hydrogen-rich hydroxyethyl starch (H-HES); hypertonic saline/hydroxyethyl starch (HSH); and hydrogen-rich hypertonic saline/hydroxyethyl starch (H-HSH). At 72 h after successful resuscitation, lung tissue was Hematoxylin Eosin stained to score any pathologic changes. We also determined wet-to-dry (W/D) lung weight ratios and lung tissue concentrations of interleukin (IL)-6, tumor necrosis factor (TNF) alpha, IL-10, malondialdehyde (MDA), and superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. RESULTS: Compared with the non-H groups, polymorphonuclear neutrophil accumulation in alveoli in the H groups was significantly reduced (P value), and capillary leakage and wall edema were ameliorated. Compared with the sham group, pathologic pulmonary injury scores, W/D ratios, IL-6, TNF-alpha, IL-10, MDA concentrations, and MPO activity in the other groups were all increased, whereas SOD activity was decreased (P < 0.01). Comparing the H-Ringer, H-HES, and H-HSH groups respectively with the Ringer, HES, and HSH groups, pathologic pulmonary injury scores, W/D ratios, IL-6, TNF alpha, MDA concentrations, and MPO activity were all reduced, whereas IL-10 concentrations and SOD activity were increased (P < 0.01). CONCLUSIONS: Each hydrogen-rich liquid resuscitation preparation could protect the lung against acute injury secondary to UHS. These mechanisms may be associated with hydrogen inhibiting the release of pro-inflammatory cytokines, promoting anti-inflammatory cytokine release, and reducing oxidative damage. PMID- 25130774 TI - Dakin solution alters macrophage viability and function. AB - BACKGROUND: Macrophages are important in wound defense and healing. Dakin's solution (DS), buffered sodium hypochlorite, has been used since World War I as a topical antimicrobial for wound care. DS has been shown to be toxic to host cells, but effects on immune cells are not well documented. MATERIALS AND METHODS: DS at 0.5%, 0.125%, and ten-fold serial dilutions from 0.25%-0.00025% were evaluated for cellular toxicity on murine macrophages (J774A.1). The effect of DS on macrophage adhesion, phagocytosis, and generation of reactive oxygen species was examined. Macrophage polarization following DS exposure was determined by gene expression using quantitative real-time polymerase chain reaction. RESULTS: Concentrations of DS >0.0025% reduced macrophage viability to <5% in exposure times as short as 30 s. Similarly, phagocytosis of Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus flavus were significantly reduced at all tested concentrations by macrophages pretreated with DS. H2O2 production was reduced by 8%-38% following treatment with 0.00025%-0.125% DS. Macrophage adherence was significantly increased with >0.0025% DS after 15 min of exposure compared with controls. Quantitative real-time polymerase chain reaction demonstrated that DS exposure resulted in classical macrophage activation, with increased expression of inducible nitric oxide synthase 2, interferon-gamma, and interleukin (IL)-1beta. CONCLUSIONS: DS at clinically used concentrations (0.025% 0.25%) was detrimental to macrophage survival and function. For optimal clinical use, understanding the impact of DS on macrophages is important as depletion may result in impaired pathogen clearance and delayed healing. These findings indicate that 0.00025% DS is a safe starting dose; however, optimal use of DS requires further validation with in vivo models. PMID- 25130775 TI - Risk factors for late-onset neutropenia after rituximab treatment of B-cell lymphoma. AB - OBJECTIVES: Late-onset neutropenia after rituximab (RTX) therapy (R-LON) has been widely reported, but clinical studies on a large number of cases are limited. In this study, we aimed to investigate the incidence and risk factors of R-LON. PATIENTS AND METHODS: In this study, we retrospectively analyzed data of 213 enrolled B-cell lymphoma patients (male 114; female 99) treated with RTX at a single institution. R-LON was defined as otherwise unexplained grade III-IV neutropenia after RTX. The median age of the patients was 62 years, and 129 of them were initially diagnosed at advanced stages (stage III-IV). RESULTS: R-LON occurred in 19 patients within a median of 121 (range, 49-474) days after the last RTX administration. The 1-year cumulative incidence was 9.0%. On univariate analysis, older age (>60 years), advanced stage, and purine analog or methotrexate administration were significant or borderline significant risk factors for R-LON, whereas sex, disease type, bone marrow invasion, combination with cytotoxic chemotherapeutic drugs, intensified therapy (compared with R CHOP), prior autologous transplantation, and repeated RTX administration were not. On multivariate analysis, older age (hazard ratio (HR), 2.95) and advanced stage (HR, 3.56) were significant risk factors. Treatment with granulocyte colony stimulating factor was feasible in grade IV R-LON patients with high risk of infection. DISCUSSION AND CONCLUSION: Careful follow-up is therefore necessary after B-cell lymphoma treatment, especially in high-risk patients with advanced disease or of older age. PMID- 25130776 TI - 6-Bromoindirubin-3'oxime (BIO) decreases proliferation and migration of canine melanoma cell lines. AB - Despite recent therapeutic advances, malignant melanoma is an aggressive tumor in dogs and is associated with a poor outcome. Novel, targeted agents are necessary to improve survival. In this study, 6-bromoindirubin-3'-oxime (BIO), a serine/threonine kinase inhibitor with reported specificity for glycogen synthase kinase-3 beta (GSK-3beta) inhibition, was evaluated in vitro in three canine melanoma cell lines (CML-10C2, UCDK9M2, and UCDK9M3) for beta-catenin-mediated transcriptional activity, Axin2 gene and protein expression levels, cell proliferation, chemotoxicity, migration and invasion assays. BIO treatment of canine malignant melanoma cell lines at 5 uM for 72 h enhanced beta-catenin mediated transcriptional activity, suggesting GSK-3beta inhibition, and reduced cell proliferation and migration. There were no significant effects on invasion, chemotoxicity, or apoptosis. The results suggest that serine/threonine kinases may be viable therapeutic targets for the treatment of canine malignant melanoma. PMID- 25130778 TI - Emotional perception and theory of mind in first episode psychosis: the role of obsessive-compulsive symptomatology. AB - The aim of the present study was to investigate the effects of comorbid obsessive compulsive symptoms on emotional perception and theory of mind (ToM) in patients with first-episode psychosis. Participants were 65 patients with non-affective first episode psychosis (FEP) and 47 healthy controls. The patient group was divided into two subgroups, those with (FEP+; n=38) and those without obsessive compulsive symptomatology (FEP-; n=27). Emotion perception and ToM were assessed with the Perception of Social Inference Test. Severity of psychotic and obsessive compulsive symptoms was assessed with the Positive and Negative Syndrome Scale (PANSS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), respectively. Deficits in emotion recognition and theory of mind were confirmed in patients with non-affective first-episode psychosis compared to healthy controls. In patients, comorbidity with obsessive-compulsive symptoms was associated with worse performance on certain aspects of social cognition (ToM 2nd order) compared to FEP- patients. Our findings of impaired emotion perception and ToM in patients with first-episode psychosis support the hypothesis that deficits are already present at illness onset. Presence of OCS appears to have further deleterious effects on social cognition, suggesting that these patients may belong to a schizo-obsessive subtype of schizophrenia characterized by more extensive neurobiological impairment. PMID- 25130777 TI - Sensitivity of magnetic resonance imaging in the diagnosis of mobile and nonmobile L4-L5 degenerative spondylolisthesis. AB - BACKGROUND CONTEXT: Lumbar degenerative spondylolisthesis (LDS) is often diagnosed by conventional supine magnetic resonance imaging (MRI). Numerous studies have shown, however, that the degree of spondylolisthesis can be reduced or disappears when the patient is supine as compared with standing lateral and flexion-extension (SLFE) radiographs. PURPOSE: To compare the sensitivity of supine MRI with SLFE radiographs in patients with L4-L5 LDS. STUDY DESIGN: A retrospective imaging study. PATIENT SAMPLE: Included patients diagnosed with L4 L5 LDS with both SLFE films and supine MRI. METHODS: Lumbar degenerative spondylolisthesis was defined radiographically as a slip greater than 4.5 mm. Mobile LDS was defined as a difference of greater than 3% in slip percentage between lateral radiographs and sagittal MRIs. Additional measurements included L4-L5 facet effusion diameter on axial MRIs. Measurements were performed by two independent examiners. The kappa coefficient was used to assess the interobserver agreement. RESULTS: Of 103 patients assessed, 68% were women and the average age was 66 years. Lumbar degenerative spondylolisthesis was seen on 101 (98%) lateral films and 80 (78%) MRIs. Average slip was 10.0 mm for lateral standing radiographs and 6.6 mm on MRI (p<.0001). Fifty (48%) patients were identified with mobile LDS. The positive predictive value of facet joint effusion for mobile LDS increased from 52% for effusions greater than 1 mm to 100% for effusions greater than 3.5 mm. CONCLUSIONS: This study found that MRI had a sensitivity of 78% for detecting L4-L5 LDS compared with 98% for lateral standing films. We also identified facet effusion size as a marker to predict mobile LDS. These findings suggest that, particularly in the setting of facet effusions, the complete workup of patients in whom LDS is possible should include standing radiographs. PMID- 25130779 TI - Association between FYN polymorphisms and defense mechanisms in healthy Chinese Han subjects. PMID- 25130780 TI - An exploratory study of evoked facial affect in adolescent females with anorexia nervosa. AB - The aim of this exploratory study was to investigate facial affect in adolescent females with anorexia nervosa (AN). Evoked facial affect was recorded whilst AN and control participants (n=34) viewed emotional films. Significantly less facial affect was found in AN adolescents, despite reporting no differences in subjective emotion experience. These findings correspond with previous studies in adults with AN. Altered facial affect may impair interpersonal functioning and contribute to illness maintenance. PMID- 25130781 TI - Differences in personality traits between male-to-female and female-to-male gender identity disorder subjects. AB - The present study aimed to investigate differences in personality traits among male-to-female (MtF), female-to-male (FtM) gender identity disorder (GID) subjects and non-transsexual male (M) and female (F) controls. Subjects were 72 MtF and 187 FtM GID subjects without psychiatric comorbidities together with 184 male and 159 female non-transsexual controls. Personality traits were assessed using a short version of the Temperament and Character Inventory (TCI-125). Group comparisons were made by two-way ANOVA. Statistical significances were observed as follows: 1) lower novelty seeking in FtM than in M or MtF, 2) higher reward dependence in FtM than in M, 3) higher cooperativeness in FtM than in M or MtF, 4) the highest self-transcendence in MtF among all the groups. The highest self transcendence in MtF subjects may reflect their vulnerable identity and constrained adaptation to society as the minority. Nevertheless, higher reward dependence and cooperativeness in FtM subjects can be related to more determined motivation for the treatments of GID and might promise better social functioning and adjustment than MtF subjects. PMID- 25130782 TI - Association between the 9 repeat allele of the dopamine transporter 40bp variable tandem repeat polymorphism and Alzheimer's disease. AB - A case-control study was performed to investigate the association between the dopamine transporter (DAT) gene (SLC6A3) rs28363170 polymorphism and the risk for Alzheimer's disease (AD). Our results indicated a statistically significant correlation between the inheritance of the SLC6A3 9 repeat allele and the genetic susceptibility to AD in a dose-dependent manner. PMID- 25130783 TI - Why are you here again? Concordance between consumers and providers about the primary concern in recurring psychiatric visits. AB - Patient-centered care has become increasingly important over the last decade, both in physical and mental health care. In support of patient-centered care, providers need to understand consumers' primary concerns during treatment visits. The current study explored what primary concerns were brought to recurring psychiatric visits for a sample of adults with severe mental illness (N=164), whether these concerns were concordant with those recognized by providers, and which factors predicted concordance. We identified 17 types of primary concerns, most commonly medications and symptoms, with only 50% of visits showing evidence of at least partial agreement between consumers and providers. Contrary to expectations, consumer demographics, activation, trust, and perceptions of patient-centeredness were not predictive, while greater preferences for autonomy predicted poorer agreement. Our findings highlight the need for interventions to promote a shared understanding of primary concerns in recurring psychiatric visits. Further attention is needed to ensure the provision of patient-centered care such that consumer concerns are acknowledged and addressed within recurring psychiatric visits. PMID- 25130784 TI - Functional dyspepsia: outcome of focus groups for the development of a questionnaire for symptom assessment in patients suffering from postprandial distress syndrome (PDS). AB - BACKGROUND: To date, no patient reported outcomes (PRO) instrument is available for evaluation of treatment efficacy in functional dyspepsia (FD)/postprandial distress syndrome (PDS). The aim of our study was to perform focus group interviews for the development of a new questionnaire for assessing symptom pattern and severity in PDS. METHODS: Random ambulatory patients diagnosed with FD/PDS based on Rome III criteria and no predominant gastro-esophageal reflux disease (GERD) symptoms were invited to participate. Focus group sessions were organized where patients reported and discussed their symptoms, facilitated by an experienced physician. After reaching saturation of identified symptom items, questions for a pilot PRO instrument were drafted and evaluated in cognitive interviews for relevance, clarity, and consistency. KEY RESULTS: Of 225 screened patients, 26 patients were diagnosed with PDS without overlapping GERD as single final diagnosis. Fifteen of these (87% female, 48 +/- 3.2 years) participated in one of three focus groups. All (100%) confirmed experiencing symptoms that were triggered or aggravated by ingestion of a meal, corresponding to early satiation (100%), and postprandial fullness (100%). In addition reported gastroduodenal symptoms were nausea (40%, postprandial in all, interprandial in 20%), upper abdominal bloating (33%), excessive belching (27%), and vomiting (13%). Epigastric pain and burning were present in respectively 20% and 13%. Non gastroduodenal symptoms that patients reported included heartburn (33%, but mostly sporadic), weight loss (93%, on average 5.0 +/- 1.7 kg), and fatigue (67%). Questions evaluating these symptoms were validated in 15 cognitive interviews. CONCLUSIONS & INFERENCES: This focus group study confirms symptoms corresponding to postprandial fullness and early satiation as the key items for developing a PRO for PDS. PMID- 25130786 TI - Esophageal leukoplakia: a rare cause of white patches in esophagus with malignant potential. PMID- 25130785 TI - Isoselective ring-opening polymerization of rac-lactide initiated by achiral heteroscorpionate zwitterionic zinc complexes. AB - A highly isotactic stereoblock PLA has been obtained using the achiral heteroscorpionate zwitterionic zinc complexes as catalysts, for the first time, via a chain-end control mechanism. PMID- 25130787 TI - Unilateral postural tremor caused by frontal cavernoma. PMID- 25130788 TI - Analysis of biomarkers for risk of acute kidney injury after primary angioplasty for acute ST-segment elevation myocardial infarction: results of the HORIZONS-AMI trial. AB - OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) may occur after percutaneous coronary intervention (PCI). METHODS: We evaluated patients with ST elevation myocardial infarction (STEMI) undergoing emergency PCI with serial biomarkers. RESULTS: Of the 390 patients enrolled in the HORIZONS-AMI biomarker substudy, 56 (14.3%) developed AKI. In the AKI group, the levels of B-type natriuretic peptide were consistently higher than in the no-AKI group at baseline (P = 0.0327), hospital discharge (P = 0.0002), 30-day follow-up (P = 0.0193), and 1-year follow-up (P = 0.031). At hospital discharge, the AKI group had elevated biomarkers compared to the no-AKI group: D-dimer (P = 0.0066), C-reactive protein (P = 0.0468), endothelial cell-selective adhesion molecule (P = 0.0169), adiponectin (P = 0.0346), and von Willebrand factor (P = 0.0168); there was also a trend toward higher cystatin C (P = 0.0585) in the AKI group. Similar correlations between biomarker panel increase and the development of CI-AKI were consistent at baseline, 30-day, and 1-year follow-up. Chemokine (C-C motif) ligand 23 showed an opposite pattern with an increase at all time points in the no-AKI compared to the AKI group. CONCLUSIONS: The risk of CI-AKI after primary PCI for STEMI may be associated with hemostatic imbalances, activation of procoagulants, decreased endogenous anticoagulants, enhanced inflammation, platelet activation, or decreased fibrinolytic activity. PMID- 25130789 TI - Prevalence and risk factors of sexual problems and sexual distress in a sample of women suffering from chronic widespread pain. AB - INTRODUCTION: Chronic widespread pain (CWP) is a prevalent musculoskeletal problem and a cardinal symptom of fibromyalgia, affecting up to 15% of the population. CWP is associated with substantial physical and psychological impairment and reduced quality of life. AIM: To describe sexual problems in women having CWP. To compare the sexual function between patients with CWP and healthy women, and to explore potential predictors of sexual problems in women suffering from CWP. METHODS: A descriptive, cross sectional study involving a total of 853 individuals, including 166 with CWP and 687 healthy counterparts. For the screening of sexual problems and distress, the original and amended lifelong version of the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale were applied. A set of standardized questionnaires to assess potential risk factors for sexual problems was further used. MAIN OUTCOME MEASURES: The levels of sexual function and distress in women with CWP was compared with those of healthy women. Univariate and multivariate linear regression was used to determine the potential predictors for sexual problems in women with CWP and healthy counterparts. RESULTS: Women with CWP reported more difficulties with lubrication, more sexual pain, and higher levels of sexual distress. Potential predictors of sexual problems in women with CWP were heterogeneous, with relationship dissatisfaction being associated with lower levels of sexual function in all the FSFI domains. Significant, domain-specific effects were further detected for anxiety sensitivity, emotional intelligence, obsessive compulsive behavior, and the big five personality traits. In general, factors influencing recent sexual problems were different from those influencing lifelong sexual function. CONCLUSIONS: CWP patients report more sexual pain and sexual distress compared with controls. Assessment of sexual problems should therefore be added to routine care of patients with CWP. PMID- 25130790 TI - Mounier-Kuhn syndrome: a systematic analysis of 128 cases published within last 25 years. AB - BACKGROUND AND AIMS: Mounier-Kuhn syndrome is a rare disease with abnormal enlargement of major airways, but epidemiological studies are lacking, and currently the most available data about it come from case reports, making it difficult to collate changes in a particular patient to those in previously published cases. The aim of this work is to systematically review cases published in the last 25 years and to use descriptive statistics to summarize the patient demographic and clinical information therein in order to acquire details about patient clinical characteristics. METHODS: Cases published in world literature between 1987 and 2013 were sought and reviewed according to PRISMA guidelines. Cases were included only if patient's age was at least 18 years, and a computed tomography scan with tracheal measurements was available. RESULTS: An 8:1 male predominance was found in 89 identified reports (128 cases). Mean age was 53.9 years, and average tracheal diameter was 36.1 mm. No correlation between increasing age and increasing tracheal diameter was found. Bronchiectasis, tracheal diverticulosis and tracheobronchial dyskinesia were common (49.2%, 33.6% and 28.9%, respectively). Cough, dyspnea and recurrent respiratory infections (71.1%, 51.6% and 50.8%, respectively) were the most common complaints. CONCLUSIONS: The data confirm that syndrome mostly manifests with nonspecific respiratory symptoms and is significantly more common in males. Importantly, there was no connection between age and airway diameter, a fact that could mean that the enlargement does not progress over time, and its severity depends on some other yet undetermined factors. PMID- 25130791 TI - Stop adding metal layers: Will bioabsorbable scaffolds become the gold standard for late in-stent restenosis and neo-atherosclerosis? AB - The optimal management of instent restenosis has yet to be fully clarified. Drug eluting balloons are a popular strategy, but a new stent is preferred when dilatation gives a suboptimal result because of insufficient extrusion of neointimal tissue. There is concern for adding multiple permanent metallic layers to the vessel wall, especially in small vessels. The use of bioabsorbable vascular scaffolds appears an appealing alternative strategy, since it scaffolds the neointimal tissue without further adding metal struts to the vessel wall. PMID- 25130792 TI - A comprehensive immunohistochemistry algorithm for the histological subtyping of small biopsies obtained from non-small cell lung cancers. AB - AIMS: Need for accurate histologic subtyping of non-small cell lung carcinomas (NSCLCs) is growing. IHC patterns may be ambiguous in some cases, rendering it difficult to determine subtypes. METHODS AND RESULTS: Tissue microarrays composed of 184 resected NSCLCs were stained for TTF-1, Napsin A, CK7, p40, p63, CK5/6, and mucicarmine. TTF-1 and Napsin A were chosen as the most accurate adenocarcinoma (ADC) marker (ACM), and p40 as squamous cell carcinoma (SCC) marker (SCM). We then prospectively performed IHC using these markers (TTF-1, Napsin A, and p40) in a cohort of small NSCLC biopsies (n = 186) with ambiguous morphology. Of these biopsies, 82.8% (154/186) were classifiable into either ADC or SCC by applying '3-marker IHC panel'. Additional CK7, p63, and CK5/6 were applied in 30 biopsies with equivocal IHC patterns, including 18 ACM-/SCM- (double-negative) and 12 ACM+/SCM+ (double-positive) cases. Decision tree and support vector machine models revealed that TTF-1 was a critical single marker for ADC in double-positive cases (91.7% accuracy), whereas p63 and/or CK5/6 helped to subtype double-negative cases (72.2% accuracy). CONCLUSIONS: We propose a novel comprehensive algorithm for subtyping NSCLCs using a 3-marker IHC panel and additional p63 and CK5/6 that would be useful for subtyping small NSCLC biopsies. PMID- 25130794 TI - Footprints of cardiac mechanical activity as expressed in lung Doppler signals. AB - AIMS: To determine the diagnostic information contained in cardiac pulsatile pressure waves as expressed in the Doppler signals recorded over the right lung. METHODS AND RESULTS: The pulsatile characteristics of the pulmonary vascular system were studied by means of the novel pulse Doppler technology in 38 control volunteers, 31 patients with atrial fibrillation (AF) and 7 patients with atrial flutter. The Doppler velocity waveforms recorded were interpreted in relation to the cardiac cycle mechanical events that generate them: Ventricular systole (S), diastole (D) and presystolic left atrial contraction (A). It was demonstrated that in all cases of AF, wave-A was absent. With longer diastole a high frequency velocity waves were visible. It is assumed that they represent the atrial mechanical fibrillation. In the patients with atrial flutter, the single A-wave was replaced by a waveform termed F, the frequency of which exactly matched that of the flutter wave on the ECG. The F-wave had both a positive and negative component. CONCLUSION: The lung Doppler signals contain distinct signatures typical of arrhythmias such as AF and atrial flutter that can be used for both diagnosis and to gain insight into the nature of the phenomena. PMID- 25130793 TI - Weight's up? Predictors of weight-related communication during primary care visits with overweight adolescents. AB - OBJECTIVE: Physicians' use of Motivational Interviewing (MI) techniques when discussing weight with adolescent patients is unknown. METHODS: We coded audio recorded encounters between 49 primary care physicians and 180 overweight adolescent patients. During weight discussions, we used the MITI 3.0 to assess: Empathy, MI Spirit, open-ended questions, reflections, MI consistent behaviors (e.g., praising) and MI inconsistent behaviors (e.g., confronting). We examined associations of patient and physician characteristics with (1) MI techniques, (2) time discussing weight, and (3) encounter time. RESULTS: Physicians used more MI consistent techniques with female patients (p=0.06) and with heavier patients (p=0.02). Physicians with prior MI training also used more MI consistent techniques (p=0.04) and asked more open-ended questions (p=0.05). Pediatricians had a higher MI Spirit score than family physicians (p=0.03). Older patient age was associated with physicians spending less time discussing weight-related topics (p=0.04) and higher BMI percentile was associated with physicians spending more time discussing weight-related topics (p=0.01). Increased use of MI inconsistent techniques was associated with longer encounters (p=0.02). CONCLUSION: Physicians' weight discussions vary based on adolescent and physician characteristics. Importantly, not using MI lengthened encounter time. PRACTICE IMPLICATIONS: Physicians might consider using MI techniques more and attempt to use these equally with all adolescents. PMID- 25130795 TI - High expression of Beclin-1 predicts favorable prognosis for patients with colorectal cancer. AB - PURPOSE: Beclin-1 is an autophagy gene. It promotes the formation of the autophagic vesicle as well as plays an essential role in guarding the cells against chromosomal instability. Overexpression of Beclin-1 has been reported to predict a favorable survival in various cancers. However, little is known about its prognostic significance in colorectal cancer. METHODS AND MATERIALS: A total of three hundred and sixty-three (363) colorectal tissues from colorectal cancer (CRC) patients were collected. Tissue micro-arrays and immunohistochemistry were used to investigate the expression and prognostic significance of Beclin-1 in CRC. The associations among Beclin-1 expression, clinicopathological parameters and prognosis were evaluated. RESULTS: Beclin-1 had a higher expression in CRC tissues than in normal tissues. A high expression of Beclin-1 was positively correlated with gender (P=0.027), histological grade (P=0.003), pM status (P=0.003) and clinical stage (P=0.024). Patients with a high Beclin-1 expression, when compared to those with a lower expression had both a better overall survival (OS, P=0.006) and disease-free survival (DFS, P=0.008). In the pT3 subgroup, Beclin-1 was also found to be a good prognostic indicator (P<0.05). Multivariate analysis showed a high expression of Beclin-1 was indeed a positive independent prognostic factor of OS and DFS for CRC patients (P<0.05). CONCLUSION: Our results demonstrated that a high expression of Beclin-1 correlated with a better overall survival and disease-free survival, thus serving as a favorable independent prognostic marker in CRC. PMID- 25130796 TI - Aspirin may reduce liver fibrosis progression: Evidence from a multicenter retrospective study of recurrent hepatitis C after liver transplantation. AB - BACKGROUND AND AIMS: There is evidence for an association between thrombosis in the hepatic microcirculation and liver fibrosis. The aim of this study was to evaluate the role of daily low-dose aspirin (75 or 100mg, given for prevention of hepatic artery thrombosis) in fibrosis progression to >= F2 fibrosis score in liver-transplant recipients with recurrent hepatitis C virus (HCV). METHODS: All HCV-positive patients who had undergone liver transplantation (LT) between 2000 and 2010 were included. Exclusion criteria were negative HCV RNA, previous LT or death within a year of LT. Liver fibrosis was assessed by histological evaluation. Data were censored at the date of the last histological evaluation before starting anti HCV therapy. Progression to fibrosis F >= 2 was analyzed with a multistate model with time-dependent covariables. RESULTS: One hundred and eighty-eight patients were included. In univariate analysis, older recipient and donor age, male donor gender, activity score >= A2 after LT, number of steroid boluses and aspirin intake (HR: 0.75 [0.57-0.97]; P=0.03) influenced the risk of progression to fibrosis >= F2. In multivariate analysis, adjusted on site, older donor age, male donor gender, activity score >= A2 and number of steroids boluses, remained independent predictors of fibrosis progression, while younger recipient age and aspirin intake (HR: 0.65 [0.47-0.91]; P=0.01) were associated with a slower fibrosis progression. CONCLUSION: Low-dose aspirin treatment might be associated with a lower risk of liver fibrosis progression in patients with HCV recurrence after LT. PMID- 25130797 TI - [Progress and potential applications of induced pluripotent stem cell technology]. AB - Differentiated somatic cells can be reprogrammed to a pluripotent state through ectopic expression of specific transcription factors. These reprogrammed cells, which were designated as induced pluripotent stem (iPS) cells, are detected to exhibit unlimited self-renewal capacity and pluripotency. This breakthrough in stem cell research provides a powerful and novel tool for the studies on pathogenesis of diseases, reprogramming mechanism and development of new therapies. For this reason, the iPSC technology has currently become one of the hot topics in stem cells research. Recently, major progress in this field has been achieved: initially, researchers succeeded in inducing the reprogramming of mouse fibroblasts by retroviral transduction of four specific transcription factors; in succession, the accelerated development of iPSC technology by employing non-integrating viral vectors, non-viral vectors or removing the introduced foreign genes via gene knock-out has ensured the yields of much safer iPSC; meanwhile, some researches discovered the proofs that a number of micro molecular compounds were potent in accelerating the cellular reprogramming. For a prospect, iPSC are highly promising for regenerative medicine, disease modeling and drug screening. In this review, the recent progress in the generation of iPSC, prospects of their possible clinical applications and problems in the iPSC research are summarized and discussed. PMID- 25130798 TI - [Frequently ABL kinase domain G:C->A:T mutation and uracil DNA glycosylase abnormal expression in TKI-resistant acute lymphoblastic leukemia of Chinese population]. AB - Most Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) patients often show rapid recurrence and development of ABL kinase domain (KD) mutation after tyrosine kinase inhibitor (TKI) treatment. To further investigate the mechanism of Ph(+) ALL fast relapse after TKI treatment, ABL KD mutation in 35 Chinese Ph(+) ALL with TKI resistance was detected by direct sequencing. The results showed that 77.1% (27/35) Ph(+) ALL patients with TKI resistance had ABL KD mutation and 55.6% (15/27) Ph(+) ALL patients with ABL KD mutation had T315I. Interestingly, 77.8% (21/27) Ph(+)ALL showed ABL mutation G: C->A:T, including T315I, E255K and E459K. Furthermore, all the Ph(+) ALL patients with two or more ABL KD mutations collaborated with complex chromosome abnormality and all the TKI resistant Ph(+) ALL patients, whose karyotype progressed from simple t (9;22) into complex, developed ABL KD mutation. Moreover, the expression level of uracil DNA glycosylase UNG2, which inhibits G:C->A:T transition in genomic DNA, decreased in Ph(+) ALL with TKI-resistance compared to that in newly diagnosis Ph(+) ALL. It is concluded that there is a high frequent ABL KD G:C->A:T mutation and a high genomic instability in Chinese TKI-resistant Ph(+) ALL. In addition, the decreased UNG2 expression in TKI-resistant Ph(+) ALL probably contributes to their high rate of ABL KD G:C->A:T mutation. PMID- 25130800 TI - [Expression of G-CSFR IV isoform in adult acute myeloid leukemia and its clinical significance]. AB - This study was aimed to investigate the expression of granulocyte colony stimulating factor receptor IV(G-CSFR IV) in adult acute leukemia patients and its clinical significance. The bone marrow hematopoietic stem cells from healthy persons were used as controls. The real-time RT-PCR was used to determine the expression level of G-CSFR I-IV in 99 AML, 34 ALL patients and 19 healthy persons. The results showed that the relative expression level of G-CSFR IV/G CSFR I in AML patients was obviously elevated, as compared with that in ALL patients and controls, while the relative expression level of G-CSFR IV/G-CSFR I in ALL patients showed no statistical difference from controls. The analysis of clinical features and chemotherapeutic efficacy demonstrated that the clinical remission rate in patients with high expression of G-CSFR IV/G-CSFR I was lower than that in patients with low expression. The relative expression level of G CSFR IV/G-CSFR I was not related with risk stratification from sex, age, blast ratio, FAB typing, chromosome and fusion gene. It is concluded that the abnormal high expression of G-CSFR IV relates with poor prognosis of AML. PMID- 25130799 TI - [Effects of Sam68 gene silence on proliferation of acute T lymphoblastic leukemia cell line Jurkat]. AB - This study was purpose to investigate the effect of Sam68 gene silence on proliferation of human acute T lymphoblastic leukemia cell line Jurkat. The sequence of shRNA targeting the site 531-552 of Sam68 mRNA was designed and chemically synthesized, then a single-vector lentiviral, Tet-inducible shRNA Sam68 system (pLKO-Tet-On) was constructed; next the Jurkat cells were infected with lentivirus to create stable cell clones with regulatable Sam68 gene expression. The inhibitory efficiency of Sam68 gene was assayed by Real-time PCR and Western blot; the cell activity of Jurkat cells was detected with MTT assay; the change of colony forming potential of Jurkat cells was analyzed by colony forming test; the cell cycle distribution was tested by flow cytometry. The results indicated that the expression of Sam68 in experimental cells was statistically decreased as compared with that of the control cells; the cells activity and colony forming capacity of the Jurkat cells with Sam68 gene silence were significantly inhibited; with Sam68 gene silencing, the percentage of S phase cells was significantly increased, while the percentage of G2 phase cells was significantly decreased. It is concluded that the silencing Sam68 gene using shRNA interference can effectively inhibit the proliferation of human acute T lymphoblastic leukemia cell line Jurkat. PMID- 25130802 TI - [Bioinformatic analysis of chronic myeloid leukemia progression and preliminary experimental verification]. AB - This study was aimed to explore the progression mechanism of chronic myeloid leukemia, so as to provide the new molecular markers for evaluation of CML clinical outcome and selection of treatment. The microarray data of genes related with progression from different phase of chronic myeloid leukemia (CML) were collected from public data depository GEO (Gene expression datasets). SAM analysis, fold change filtering, cross comparison were used to analyze the data and identify different genes. Moreover, MeV and pSTIING sofewares were used to analyze the key differential genes and signal pathways. At last, Q-PCR were used to confirm the predicted key gene. The results indicated that after comparison, 9 genes were differentially expressed from AP to BC, and the integrin-mediated cell adhesion , focal adhesion, regulation of actin cytoskeleton were the principal pathways during CML progression. Network construction analysis found that AP related genes or pathways may be the original signals; and MLLT4, WDR35 and EPHB4 were the key genes for CML progression. EPHB4 was confirmed by Q-PCR in CML BC patients and CP patients. It is concluded that MLLT4, WDR35, EPHB4, integrin mediated cell adhesion, focal adhesion and regulation of actin cytoskeleton are the principal genes and pathways during CML progression. PMID- 25130801 TI - [Construction of IK6 recombinant lentiviral vector and its expression and biologic feature in THP1 cells]. AB - The purpose of this study was to construct a lentiviral vector carrying IK6 gene and to observe the expression of IK6 as well as related biologic feature in THP1 cells, so as to provide an effective method to further investigate the role of this gene in leukemia. The IK6 gene was obtained by using reverse transcription polymerase chain reaction (RT-PCR). Then IK6 was recombined with the pGC-FU vector to construct a recombinant lentiviral vector named pGC-FU-IK6 gene GFP,which was confirmed by PCR and sequencing. The 293T cells were transfected with pGC-FU- IK6-GFP by using Lipofectamine 2000. After examining the titer of the virus, pGC-FU- IK6-GFP was used to transfect THP1 cells. The transfection efficiency was detected by flow cytometry, and the expression level of mRNA and IK6-GFP fusion protein were confirmed by RT-PCR and Western blot respectively. Then the impact of IK6 on apoptosis and cell cycle was analyzed. The results showed that the IK6 gene was obtained by RT-PCR and connected into the linearized lentiviral vector to successfully constructed target plasmid named pGC-FU-IK6-GFP with Amp resistant. The target plasmid was transfected into 293T cells and the virus titer was 2.0*10(9)TU/ml. Next, THP1 cells were transfected with pGC-FU-IK6 GFP and the efficiency was up to 90%. The detection of the IK6 mRNA and IK6-GFP fusion protein in target cells showed that IK6 could promote target cell clone formation and inhibit apoptosis, but had no significant effect on the cell cycle. It is concluded that virus vector carrying IK6 gene had been successfully constructed and expressed in THP1 stably. Biology studies of target THP1 cell shows that the IK6 is likely to interfere with the function of normal Ikaros protein as tumor suppressor, and it exerts a potential anti-apoptotic effect. Thus, IK6 can promote leukemia cell growth. However, there is no significant effect on the cell cycle. It provides an effective method for exploring the function of IK6 in acute myeloid leukemia. PMID- 25130803 TI - [Comparison and analysis between CLL-hBMSC and N-hBMSC]. AB - This study was purpose to compare and analyze the chronic lymphocytic leukemia human bone marrow stromal cells (CLL-hBMSC) and normal hBMSC (N-hBMSC) so as to provide theoretical evidence for establishment of CLL-hBMSC interaction model to imitate CLL microenvironment. Mononuclear cells (MNC) were isolated from bone marrow of CLL patients and healthy donors and then were cultured, hBMSC were established by expanding for at least five passages. The mRNA expression of adhesion molecules, such as vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), was analyzed by real-time PCR. The mRNA and protein expression of lymphotoxin beta receptor (LTbetaR) were determined by real-time PCR and Western blot, respectively. The individual NF kappaB members at protein level of CLL-hBMSC and N-hBMSC were examined by Western blot. The effect of LTalpha1beta2 on individual NF-kappaB family members at protein level in CLL-hBMSC and N-hBMSC was also examined by Western blot. The death of CLL cells was determined by flow cytometry with PI staining when cultured with or without CLL-hBMSC and N-hBMSC at different time points. The results showed that the hBMSC could be established successfully from bone marrow of CLL patients, which were similar to N-hBMSC. Adhesion molecules, such as VCAM 1 and ICAM-1, were found to be expressed at similar mRNA levels in CLL-hBMSC and N-hBMSC. LTbetaR expressions at mRNA and protein levels were comparable between CLL-hBMSC and N-hBMSC. The protein expression of the individual NF-kappaB family members could be detected in CLL-hBMSC and N-hBMSC with similar expression levels. LTalpha1beta2 stimulation activated both the classical ( RelA/p50 ) and alternative ( RelB/p52 ) NF-kappaB complexes in CLL-hBMSC and N-hBMSC. The capacities of CLL-hBMSC and N-hBMSC to protect CLL cell survival were similar. It is concluded that there is no statistical difference between bone marrow from healthy donors and CLL patients in the efficiency of generating of hBMSC. LTbetaR NF-kappaB signaling molecules are expressed and activated on hBMSC with a similar pattern. PMID- 25130804 TI - [Expression of TFPI-2 gene and its promoter methylation in acute myeloid leukemia]. AB - The aim of this study was to detect the mRNA expression of tissue factor pathway inhibitor-2 ( TFPI-2) and its methylation in bone marrow mononuclear cells from acute myeloid leukemia (AML) patients and to explore its significance in AML. Bone marrow mononuclear cells were isolated from newly diagnosed AML patients (n = 33), complete remission AML patients (n = 19), relapsed/refractory AML patients (n = 12) and iron deficiency anemia patients (control group, n = 15). Expression of TFPI-2 mRNA was detected with real-time quantitative PCR (RT-PCR) and the methylation of CpG island in its promoter was detected with methylation-specific PCR (MSP). The results showed that the expression of TFPI-2 mRNA in newly diagnosed AML, complete remission AML and relapsed/refractory AML patients was much lower than that in the controls (P < 0.05). Furthermore, its expression in relapsed/refractory AML patients was lower than that in newly diagnosed AML patients (P = 0.006). Compared with complete remission AML patients, the expression of TFPI-2 mRNA in newly diagnosed AML patients was significantly reduced (P = 0.030). The percentage of TFPI-2 promoter methylation in AML patients was 64.63% (42/64). In newly diagnosed AML group, complete remission AML group and relapsed/refractory AML group,the percentages of TFPI-2 promoter methylation were 66.67% (22/33), 52.63% (10/19) and 83.33% (10/12) (P > 0.05), respectively. The optical density ratio of TFPI-2 mRNA expression was 0.165 (0.005-2.099) in methylated AML patients, and 0.597 (0.011-2.787) in unmethylated AML patients (P < 0.05). Methylation of TFPI-2 gene promoter was not detected in control patients. After 2 courses of chemotherapy, the level of TFPI-2 mRNA was much higher in the CR group than that in the non-CR group (P < 0.05). It is concluded that the down-regulation or silence of TFPI-2 gene potentially results from its promoter methylation, and the expression level of TFPI-2 and the methylation status of its promoter may be used as indicators of risk stratification and evaluation of disease progress. PMID- 25130806 TI - [Anti-leukemia mechanism of miR-17 and miR-20a silencing mediated by miRNA sponge]. AB - This study was aimed to quantitatively detect the expression levels of pre-miR-17 and pre-miR-20a in acute leukemia patients and eight kinds of leukemia cell lines, and to investigate the anti-leukemia mechanism of miR-17 and miR-20a silence mediated by miRNA Sponge. Quantitative real-time PCR was used to detect the mRNA expression levels of pre-miR-17 and pre-miR-20a in patients with various types of leukemia and leukemia cell lines. The Jurkat cells over-expressing miR 17 and miR-20a were transfected with recombinant lentivirus-transfecting units targeted at miR-17 and miR-20a plus 6 ug/ml of polybrene. Then the proliferation ability and cell cycle of Jurkat cells was evaluated by CCK-8 and flow cytometry respectively. The results showed that the expression level of pre-miR-17 and pre miR-20a in all leukemia patients was significantly higher than that in normal group(P < 0.05), the expression of pre-miR-17 and pre-miR-20a in acute lymphoid leukemia was significantly higher than that in acute myeloid leukemia(P < 0.05), and the pre-miR-17 and pre-miR-20a expression level did not correlate significantly with high white blood cell count>20.0*10(9)/L(P > 0.05). The miR-17 and miR-20a silencing mediated by miRNA Sponge led to a significant decrease of cell growth, restored G1 accumulation and increase of cell apoptosis. It is concluded that the expression of miR-17 and miR-20a is upregulated in leukemia patients, which may contribute to leukemogenesis. Over-expressed miR-17 and miR 20a promote cell growth and cell cycle progression, and inhibit apoptosis through negatively-regulating P21 and E2F1 after-transcriptionally. PMID- 25130805 TI - [Expression of BCR/ABL fusion gene in circulating endothelial cells from chronic myelogenous leukemia patients and its clinical significance]. AB - Several studies have shown that the tumor endothelial cells are different from the normal tissue endothelial cells. These tumor endothelial cells may contribute to tumor neo-vasculogenesis. This study was purposed to analyze the biologic features and determine the expression level of CD133 and BCR/ABL fusion gene in circulating endothelial cells (CEC) isolated from peripheral blood of CML patients, as well as to investigate the role of CEC in disease progression. Mononuclear cells were isolated from peripheral blood by density gradient centrifugation; CEC were sorted by MACS and harvested in the endothelial growth medium. The morphologic features of CEC were observed by microscopy, the cell growth rate was calculated by cell counting, and the cells were identified by immunofluorescence staining for the expression of CD31,CD34,VWF and CD133. The expression of BCR/ABL fusion gene was examined by FISH in 12 CML patients. The results indicated that the isolated CEC displayed the typical cobble-stone morphology. These cells could be identified by the positive immunofluorescence staining for CD31, CD34 and VWF, and showed more increased proliferative potential as compared to that of healthy donors. It was found that the positive rate of CD133 was 31.29% in CML patients, which was significantly different from that of healthy donors (P < 0.05). In 12 CML patients, CEC carried the same chromosome aberration as the leukemia cells (10.77%). Higher expression level of CD133 and BCR/ABL fusion gene positively correlated with progression of disease. It is concluded that the CEC may participate in invasion and angiogenesis in patients with CML and possibly correlate to the spreading and progression of the disease. PMID- 25130807 TI - [Silence potentiates chemosensitivity of K562 cells to SAHA]. AB - Ribosomal protein S27a (RPS27a) can perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The RPS27a gene has been reported to be over-expressed in breast fibroadenomas, colorectal and renal cancers, advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. This study was purposed to explore the function of RPS27a in CML-erythroleukemia cell line K562 cells. RPS27a was silenced by short hairpin RNA (shRNA) in K562 cells. Furthermore, the proliferation changes of K562 cells was detected by MTT method after silencing the RPS27a with suberoylanilide hydroxamic acid (SAHA), then the IC50 of K562 sh1/sh2 and K562-scr cells to SAHA was measured. The results indicated that compared with K562-scr cells, the IC50 of K562-sh1/sh2 to SAHA at 24 h and 48 h decreased (P < 0.01); RPS27a silence significantly increased the percentage of apoptotic K562-sh1/sh2 cells after incubation with 1 umol/L, 2 umol/L and 5 umol/L SAHA for 24 h and 48 h as compared with that of K562-scr cells (P < 0.01). K562-sh1, K562-sh2 and K562-scr cells after incubation with or without 2 umol/L SAHA for 48 h presented apoptosis features: i. e. chromatin condensation, nucleic fragmentation and apoptotic body formation. It is concluded that RPS27a can inhibit the apoptosis of K562 cells and RPS27a silence can potentiate sensitivity of K562 cells to SAHA. PMID- 25130808 TI - [Effects of As2O3 in combination with TPA on K562 cells]. AB - This study was aimed to investigate the effects of arsenic trioxide (As2O3) combined with TPA on cell cycle, cell differentiation and apoptosis of K562 cell line, and their possible mechanisms. K562 cells were treated with 200 nmol/L TPA, 2 umol/L As2O3 alone and 200 nmol/L TPA combined with 2 umol/L As2O3. The proliferative inhibition rates were determined with CCK-8. Annexin V and agarose gel electrophoresis were adopted to detect apoptosis. Colony formation test was used to determine the colony-formation efficiency. Flow cytometry was used to detect the cell differentiation and cell cycle changes. Western blot was employed to detect the expression of P38 and p-P38 proteins. The results showed that combination treatment had synergistic effects on the proliferative inhibition and apoptosis, which were much higher than those treated alone. As2O3 could decrease the colony formation ability of K562 cells. The cells treated with both TPA and As2O3 expressed far more CD11b antigens compared with cells exposed to As2O3 alone. K562 cells treated with TPA were arrested in G1 phase compared with the control group, As2O3 increased the percentage of K562 cells in the G2 phase. The combination treatment increased the expression of p-P38 of K562 cells compared with the cells exposed As2O3 alone. It is concluded that TPA can enhance the effect of As2O3 on inducing apoptosis and adjusting cell cycle , which will expect to provide a new therapeutic program. PMID- 25130809 TI - [Clinical analysis of acute myeloid leukemia with t(8;21) (q22;q22) and loss of Y chromosome]. AB - This study was aimed to investigate the clinical characteristics of acute myeloid leukemia (AML) with t (8;21) (q22;q22) and loss of Y chromosomes. Clinical data of 267 cases of AML were collected from January 2010 to June 2013. Among 267 AML, there were 13 cases with t (8;21) (q22;q22) and loss of Y chromosomes. The clinical data including clinical indicators, treatment protocols, curative effect and prognosis were analyzed retrospectively. The results showed that after normalized chemotherapy, there were 4 patients with complete remission at the first cycle of treatment, 4 patients with complete remission at the second cycle, 4 patients with complete remission at the third cycle, but one patient without complete remission after 4 cycles. There were 6 patients who did not relapse during consolidation and intensive therapy. Among these 6 patients, 4 cases accepted chemotherapy combined with transplantation, other 2 cases accepted chemotherapy. In the remainder 6 patients, 4 cases relapsed once, one cases relapsed twice, 1 cases relapsed for three times. Moreover, 2 cases who accepted the chemotherapy and auto-hematopoietic stem cell trans-plantation, were diagnosed as relapse, after accepted allo-hematopoietic stem cell transplantation, currently are in disease-free status. In follow-up period, the relapse-free survival (RFS) time was 4.67 +/- 3.45 months in chemotherapy group, the RFS time is 34.17 +/- 21.37 months in chemotherapy and transplantation group. The chemotherapy combined with transplantation extended the RFS time (P < 0.05). It is concluded that the NCCN guide indicates that AML with t (8;21) ( q22;q22) showed a good prognosis. but the clinical course of treatment confirmed that the prognosis of AML patients with t (8;21) (q22;q22) and loss Y chromosomes is poor, including uneasy remission and easy relapse, for improving the prognosis of these patients, the hematopoietic stem cell transplantation should be recommended. PMID- 25130810 TI - [Analysis of efficacy and prognosis of induction chemotherapy in 76 elderly patients with acute myeloid leukemia (non-APL)]. AB - This study was purposed to investigate the clinical features, diagnosis, treatment and prognosis of elderly patients with acute myeloid leukemia (AML) (non-APL). The clinical data of 76 elderly ( >= 60 old years) AML (non-APL) patients from January 2000 to January 2010 were analyzed retrospectively. According to treatment methods,the 76 patients were divided into 2 groups: induction chemotherapy group (51 cases) and best supportive treatment group (25 cases). The patients in induction chemotherapy group received the cytarabine based induction chemotherapy regimens, including DA, MA, HA, IA and CAG; the patients in best supportive treatment group received supportive treatment including hydroxyurea, blood transfusion and so on. The clinical features, diagnosis, treatment and prognosis between 2 groups were compared. The results showed that the median survival times of patients in induction chemotherapy and best supportive treatment groups were 5 (0.2-89) and 3 (0.1-17) months respectively, there was significantly statistical difference in median survival time between 2 groups(P < 0.01) suggesting that the induction chemotherapy obviously prolonged the survival time of elderly CML patients. The 5 patients in induction chemotherapy group survived more than 60 months, one of them survived more than nine years. After the first cycle of chemotherapy, the complete remission (CR) rate of patients was 19.6% (10/51), partial remission (PR) rate was 19.6% (10/51), the overall response rate (ORR) was 39.2%, the mortality of patients in induction remission stage was 13.7% (7/51) in induction chemotherapy group; no 1 case in best supportive treatment group reached to CR. The CR rate of patients by using MA regimen was 44.4% and its ORR was 55.5%, which was higher than that by using DA, HA, IA and CAG regimens. The median chemotherapy cycles were 3 (1-14). The follow-up found that the 3 months-survival rate of patients was 65% and 42%, the 6 month-survival rate of patients was 43% and 21%, the 1 year-survival rate of patients was 29% and 13%, the 5 year-survival rate of patients was 13% and 0% in induction chemotherapy and best supportive treatment groups respectively, showing that the survival of patients in induction chemotherapy group was better than those in best supportive treatment group. A total of 31 of out 51 cases (60.8%) in induction chemotherapy group not response to the first cycle of chemotherapy, the survival time of these patients was not statistically significantly different from that of patients in best supportive treatment group. It is concluded that the induction chemotherapy can significantly improve the prognosis of elderly patients with AML, and prolong their median survival time. The induction remission rate in elderly patients with AML is lower than that of younger patients. The MA regimen is better than DA, HA, IA and CAG, there is individual difference in the elderly patients with AML, If the first cycle of chemotherapy has not reached to CR or PR, the best supportive treatment may be considered. The low toxicity, efficient and well-tolerated chemotherapy regimens may be chosen to prolong the survival time of the elderly patients with AML (non-APL). PMID- 25130811 TI - [Effect of SU11248 on leukemia cell line K562 and its molecular mechanisms]. AB - This study was aimed to investigate the effect of SU11248 on proliferation and apoptosis of leukemia cell line K562 in vitro and its mechanism. The inhibitory effect of 3.2 ug/ml SU11248 on K562 proliferation was tested by MTT assay. The ability of SU11248 to induce apoptosis of K562 cells was examined by TUNEL and DNA ladder. The expression of C-MYC, hTERT and BCR-ABL mRNA in K562 cells was detected by RT-PCR. The protein expression of Akt and p-Akt in K562 cells was detected by Western blot. The results showed that the proliferation of K562 cells was obviously inhibited by 3.2 ug/ml SU11248 in a time-dependent manner. SU11248 could induce K562 cells apoptosis in dose-and time-dependent manner. The mRNA expression of C-MYC, hTERT and BCR-ABL was reduced significantly by SU11248 in a time-dependent manner (P < 0.05). Western blot detection showed that the expression of p-Akt protein in K562 cells decreased in dose-and time-dependent manner after SU11248 treatment, but the expression of Akt was not significantly changed. It is concluded that SU11248 can inhibit the growth of K562 cells efficiently through inducing apoptosis, its mechanism may be closely relate with the expression down-regulation of C-MYC, hTERT, BCR-ABL and the inhibition of Akt phosphorylation. PMID- 25130812 TI - [Inhibitory effect of genistein on the proliferation of Raji cells and its related mechanism]. AB - This study was aimed to investigate the anti-proliferative effect of genistein (Gen) on BCL-6 positive Raji cells and its related mechanism. Trypan blue staining and MTT method were used to analyze the anti-proliferative effect of Gen on Raji cells. Cell apoptosis, protein expression and the interaction of BCL-6 and NCoR were detected by PI/AV dual staining, Western blot and Co-IP method, respectively. The results showed that Gen had time- and dose-dependent inhibitory effect on Raji cell proliferation and induced apoptosis. Different dose of Gen had no significant effect on the expression of BCL-6 and NCoR, but could inhibit the binding of BCL-6 and NCoR. It is concluded that Gen shows inhibitory effect on BCL-6 positive lymphoma cells, which can be as a adjuvant therapy for combined rituximab with chemotherapy. PMID- 25130813 TI - [Analysis of the therapeutic efficacy and prognosis for acute myeloid leukemia M2a patients treated by IA and DA regimens]. AB - This study was purposed to compare the therapeutic efficacy and prognosis of acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA) combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine (Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our hospital were collected from May 2009 to May 2013 and analyzed. The results indicated the complete remission in IA group was slightly higher than that in DA group, there was no statistically significant difference(P > 0.05); leukocyte minimum value in IA group [(0.58 +/- 0.40)*10(9)/L] was obviously lower than that in DA group [(0.99 +/- 0.67)*10(9)/L] (P < 0.05); neutrophil minimum value in IA group [(0.19 +/- 0.09)*10(9)/L] was significantly lower than that in DA group [(0.21 +/- 0.16)*10(9)/L] (P < 0.05); the neutropenia duration in IA group (12.59 +/- 5.31)d was much longer than that in DA group (9.17 +/- 7.04)d (P < 0.05). The median survival time of patients in IA group was 36.67 months, which was obviously longer than that of patients in DA group (21.45 months) (P < 0.05). The lactate dehydrogenase (LDH) value and chemotherapy regimens were the independently risk factor affecting the prognosis of AML-M2a patients. It is concluded that as compared with DA regimen, the IA regimen can prolong the median survival time and has better long-term therapeutic efficacy, thus it can be used as the first chemotherapy regimen for treatment of AML-M2a. PMID- 25130814 TI - [Association of XRCC1 genetic polymorphism with susceptibility to non-Hodgkin's lymphoma]. AB - The purpose of this study was to explore the association between X-ray repair cross-complementing group 1 (XRCC1)gene polymorphism and non-Hodgkin's lymphoma risk. A total of 282 non-Hodgkin's lymphoma (NHL) patients and 231 normal controls were used to investigate the effect of three XRCC1 gene polymorphisms (rs25487, rs25489, rs1799782) on susceptibility to non-Hodgkin's lymphoma. Genotyping was performed by using SNaPshot method. All statistical analyses were done with R software. Genotype and allele frequencies of XRCC1 were compared between the patients and controls by using the chi-square test. Crude and adjusted odd ratios and 95% confidence intervals were calculated by using logistic regression on the basis of genetic different models. For four kinds of NHL, subgroup analyses were also conducted. Combined genotype analyses of the three XRCC1 polymorphisms were also done by using logistic regression. The results showed that the variant genotype frequency was not significantly different between the controls and NHL or NHL subtype cases. Combined genotype analyses of XRCC1 399-280-194 results showed that the combined genotype was not associated with risk of NHL overall, but the VT-WT-WT combined genotype was associated with the decreased risk of T-NHL (OR: 0.21; 95%CI (0.06-0.8); P = 0.022), and the WT-VT-WT combined genotype was associated with the increased risk of FL(OR:15.23; 95%CI (1.69-137.39); P = 0.015). It is concluded that any studied polymorphism (rs25487, rs25489, rs1799782) alone was not shown to be rela-ted with the risk of NHL or each histologic subtype of NHL. The combined genotype with mutation of three SNP of XRCC1 was not related to the risk of NHL. However, further large-scale studies would be needed to confirm the association of decreased or increased risk for T-NHL and FL with the risk 3 combined SNP mutants of XRCC1 polymorphism. PMID- 25130815 TI - [Interaction between tumor-associated macrophages (TAMs) and HUT-78 lymphoma cells]. AB - This study was aimed to explore the effects of lymphoma cells on the differentiation of monocytes from peripheral blood to tumor-associated macrophages (TAM) and the effect of TAM on proliferation of lymphoma cells in vitro, and investigate the difference between newly diagnosed lymphoma patients and healthy volunteers. Blood samples were obtained from 15 newly diagnosed lymphoma patients and 8 healthy volunteers. Monocytes from peripheral blood were isolated by Ficoll- Hypaque density gradient centrifugation and CD14 immuno magnetic beads. Then monocytes were directly co-cultured with HUT-78 lymphoma cells by using Transwell apparatus in vitro. Expression of the markers of TAM (CD68 and CD163) were detected by flow cytometry to analyse the proportion of differentiated TAM. Growth curve of HUT-78 cells was made by direct cell count. The IL-10 and VEGF levels in the co-culture system were detected by ELISA. The detection results of newly diagnosed lymphoma patients were compared with that of healthy controls. The results showed that the proportion of CD68(+), CD163(+) and CD68+CD163 (+) cells were significantly up-regulated after co-cultured with HUT 78 lymphoma cells in both patients and healthy controls (P < 0.05). There was no statistical significance in the increasing degree between patients and healthy controls. TAM differentiated from peripheral blood monocytes showed no significant promotion or inhibition on the growth of co-cultured lymphoma cells. For patients, the IL-10 and VEGF levels in the co-culture group were significantly lower than those in two single culture groups (P < 0.05) . For healthy controls, there was no significant difference between these two. It is concluded that lymphoma cells can promote the differentiation of monocytes to macrophages with M2-like phenotype. There is no difference in the promoting degree between patients and healthy controls. TAM differentiated from patients' monocytes significantly down-regulate levels of IL-10 and VEGF in the co-culture system, exhibited functions more like M1 macrophages. In contrast, TAM differentiated from monocytes of healthy controls show no such effects on the co culture system. PMID- 25130816 TI - [Clinical analysis of lymphoblastic lymphoma/leukemia treated with Hyper-CVAD/MA regimen chemotherapy combined with haploidentical hematopoietic stem cell infusion]. AB - This study was aimed to investigate the efficacy of Hyper-CVAD/MA regimen chemotherapy combined with haploidentical hematopoietic stem cell infusion for the treatment of lymphoblastic lymphoma/leukemia (LBL/ALL). Seven patients with LBL/ALL were treated in Second Artillery General Hospital from August 2009 to September 2012. All patients received programmed infusions of granulocyte-colony stimulating factor (G-CSF)-mobilized family related HLA-haploidentical donor peripheral blood hematopoietic stem cell (G-PBHSC) after each of cycle of Hyper CVAD/MA regimen chemotherapy without graft-versus-host disease (GVHD) prophylaxis. A total of four cycles of therapy were planned. The interval between each cycle of treatment was 8 to 12 weeks. By April 2014, the median follow-up time was 41 (20-57) months. The results showed that the 7 patients totally received 30 cycles of treatment, and all patients achieved complete remission (CR). The patients were generally well-tolerated to therapy, and the most significant toxicities of grade 3 to 4 neutropenia and thrombocytopenia developed in nearly all of the patients after each course of the Hyper-CVAD/MA regimen. No GVHD was observed in any of the patients during treatment. Up to now, 5 patients were still alive, 2 patients were died of relapse. It is concluded that the combination of chemotherapy and programmed haploidentical G-PBHSC infusion is a promising approach to the treatment of LBL/ALL. PMID- 25130817 TI - [Clinical analysis of 202 cases of extranodal NK/T-cell lymphoma]. AB - This study was purposed to explore the therapeutic strategy and factors influencing prognosis through the analysis of clinical characteristics, genetic aberrations, treatment and prognosis of the patients with extranodal NK/T cell lymphoma (ENKTL). A total of 202 patients with ENKL from 2005-2013 were analyzed retrospectively in term of Ann Arbor stage, B symptoms, lactate dehydrogenase (LDH), international prognostic index (IPI), beta2-microglobulin and the expression of MYC,HXO11,BCL-2. The survival was analyzed using Kaplan-Meier method, and the COX regression model was employed for multivariate analysis. The results showed that the 5 year overall survival (OS) rate and event-free survival (EFS) rate were 61.9% and 53.9% respectively; chemoradiotherapy was apparently better than chemotherapy alone for OS and EFS; OS and EFS of the patients with BCL-2 expression were apparently better than patients without BCL-2 expression; multivariant analysis by COX regression showed that Ann Arbor stage and BCL-2 expression were independent prognostic factors for EFS/OS. It is concluded that chemoradiotherapy is better than chemotherapy alone for treatment of ENKL. Ann Arbor stage and BCL-2 expression are independent prognostic factors. PMID- 25130818 TI - [Efficacy of liver transplantation for acute hepatic failure caused by reactivation of hepatitis B virus infection after chemotherapy and radiotherapy for diffuse large B-cell lymphoma]. AB - This study was aimed to investigate the morphological, biological ,clinical and therapy features in a special case of primary gastric non-Hodgkin's lymphoma (PG NHL) through analysis of PG-NHL patient who developed fulminating hepatitis following chemotherapy and radiotherapy and thus received liver transplantation (LT). The morphological changes of cells were analyzed by bone marrow smear, the expression and mutation of abnormal genes were detected by nested multiplex PCR, and HBV-DNA copies were detected by real-time fluorescence quantitative PCR (FQ PCR). The results showed that at onset of disease, patient was diagnosed as primary gastric non-Hodgkin's lymphoma (PG-NHL) with HBsAg(+) and HBVDNA(-). LUGANO stage was Ia. aaIPI score was 0.The patient was treated with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), rituximab maintenance treatment and radiotherapy. During the treatment, the patient has taken entecavir, 1 week later after the radiotherapy (2 months later after the chemotherapy), then the entecavir was discontinued. Six months later HBV DNA(+), the progressive acute hepatic failure (AHF) happened to the patient, who thus received phylogenetic right liver transplantation (LT). He has survived for 3 years after LT so far. The liver function of patient was normal more than 3 years after LT. The patient was checked regularly by PET-CT, and his PG-NHL continue complete remission(CR). It is concluded that the patients receiving chemotherapy or immunosuppressive therapy should be screened for HBV DNA, liver function and HBV reactivation signs. HbsAg positive patients should receive preventive antiviral therapy. After chemotherapy or immunosuppressive therapy, the patients should be given antiviral maintenance therapy, and the liver damage should receive the hepatoprotective and effective support treatment, LT is necessary and feasible to obtain long-term survival. PMID- 25130819 TI - [Inhibitory effect of pumpkin protein on expression of Notch signal in RPMI8226 myeloma cells]. AB - This study was aimed to explore the inhibitory effect of pumpkin protein (cucurmosin, CUS) on proliferation of RPMI8226 myeloma cells in vitro and its mechanism. Western blot was used to detect the expression level of Notch-1, Jagged-2, P-Akt and NF-KB in the myeloma cells treated by different concentrations of CUS. The results demonstrated that CUS could down-regulate the protein expression levels of Notch1, Jagged-2, P-Akt and NF-KB in the myeloma cells and with time-and concentration-dependent way, at the same time CUS could also decrease the expressions of BCL-2 and P-Akt. It is concluded that CUS can obviously inhibit the RPMI8226 cell proliferation in vitro, down-regulate the expression levels of Notch signal and its down-stream target genes. Therefore, Notch signaling pathway can be used as a new treatment target for multiple myeloma, and CUS may be become a potential new drug for regulating Notch signaling pathway. PMID- 25130820 TI - [Apoptosis-inducing effect of valproic acid combined with arsenic trioxide on RPMI 8226 cells and its mechanism]. AB - This study was aimed to investigate the apoptosis-inducing effect of valproic acid (VPA) combined with arsenic trioxide (ATO) on human multiple myeloma RPMI 8226 cells and its mechanism. The cell proliferation of RPMI 8226 cells was assayed by CCK-8 method. The cell apoptosis were detected by flow cytometry. Semiquantitative RT-PCR and Western blot were applied respectively to detect the mRNA and protein expression level of BCL-2, BAX, caspase-8 and caspase-9 gene. The results showed that both the VPA and ATO inhibited RPMI 8226 cell proliferation. The combination of ATO and VPA has synergistic effect (Q values greater than 1.15). The RPMI 8226 cell apoptosis rate in combined drug group was significantly higher than that in single drug group (P < 0.05). The mRNA and protein expressions of BCL-2 gene in combined drug group decreased, while the mRNA and protein expressions of BAX, caspase-8 and caspase-9 significantly increased, compared with single drug group (P < 0.05) . It is concluded that VPA can enhance the sensitivity of RPMI 8226 cells to ATO-induced apoptosis, which may be associated with decreasing the BCL-2 expression and increasing the BAX, caspase-8 and caspase-9 gene expression. PMID- 25130821 TI - [JAK2V617F mutation and TNF-alpha expression in myeloproliferative neoplasms and their correlation]. AB - This study was aimed to explore the JAK2V617F mutation and TNF-alpha expression in patients with myeloproliferative neoplasm (MPN), and the relation between them so as to provide theoretical basis for clinical practice and target therapy. Sixty-two confirmed BCR-ABL-negative MPN patients and 15 healthy adults were enrolled in this study. The peripheral blood mononuclear cells of the patients and healthy controls were divided into two parts, one part was used to extract DNA, the other one was used to extract mRNA and reverse-transcribe into cDNA. Real-time fluorescent quantitative PCR was used to detect JAK2V617F mutation proportion and the expression level of TNF-alpha. The results showed that the positive rate of JAK2V617F mutation in MPN patients was 64.52% (40/62) , including 54.28% in essential thrombocythemia (ET) patients (19/35), 94.74% in polycythemia vera (PV) patients (18/19) and 37.50% in myelofibrosis (MF) (3/8) patients. Mutation proportions of JAK2V617F in ET, PV and MF patients were 0.838 +/- 0.419, 4.417 +/- 0.658, 2.746 +/- 2.009 respectively. The expression of TNF alpha in ET, PV and MF patients were higher than that in healthy controls: 1.7, 7.0, 8.2-fold (P < 0.05) respectively. In addition, TNF-alpha expression was correlated with JAK2V617F allele burden (Pearson r = 0.610,R(2) = 0.372,P = 0.005). It is concluded that TNF-alpha plays an important role in the pathogenesis of MPN, the TNF-alpha expression increases and is different in ET,PV and MF patients,which correlates with JAK2V617F allele burden. PMID- 25130823 TI - [Role of Toll-like receptor 2 in primary immune thrombocytopenia]. AB - The aim of this study was to explore the role of Toll-like receptor (TLR) 2 in primary immune thrombocytopenia (ITP) by detecting TLR2 expression in the peripheral blood lymphocytes of patients with ITP and evaluating the role of TLR2 activation on inflammatory cytokine secretion. A total of 39 ITP patients and 21 normal controls were enrolled in this study. The expression of TLR2 was detected by real-time PCR and flow cytometry, and the concentration of IL-6 and TNF-alpha in culture supernatant of PBMNC treated with pam3CSK4 for 48 hours were detected by ELISA. The results showed that the expression of TLR2 mRNA in active ITP patients (3.561 +/- 0.741) was significantly higher than that in normal controls (1.750 +/- 0.314) (P < 0.05), but there was no statistically significant difference between remission ITP patients (2.333 +/- 0.448) and normal controls (P > 0.05) . Flow cytometry analysis found that the TLR2 was not expressed on T and B cells, but expressed on all monocytes both from ITP patients and normal controls. Further activation experiment showed that TLR2 activation in vitro could induce the expression of IL-6 (1644 +/- 634.0 vs 4111 +/- 525.2 pg/ml) and TNF-alpha (75.37 +/- 22.31 vs 326.0 +/- 109.9 pg/ml) in PBMNC from ITP patients (both P < 0.05), but just could promote IL-6 expression in normal controls (2119 +/- 636.9 vs 4671 +/- 315.9 pg/ml)(P < 0.05). It is concluded that the expression of TLR2 mRNA is up-regulated in PBMNC of ITP patients, and this increased TLR2 maybe participate in ITP through inducing secretion of inflammatory cytokines. PMID- 25130822 TI - [Iron chelation therapy and its influence on the alleviation of EPO resistance in MDS patients]. AB - This study was aimed to investigate the changes of erythropoietin (EPO), hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron chelation therapy, and to explore the relationship between EPO and serum ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied. The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C reaction protein (CRP) and Hb were measured respectively, the level of SF was adjusted according to the changes of CRP. Among them, there were 34 cases of low risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO, SI, TIBC, Hb levels were detected and compared before and after treatment. Besides, the difference in the incidence of EPO resistance in iron overload group and non-iron overload group was assessed before and after therapy, and 58 cases of low-risk and EPO<1 000 U/L MDS patients were given rEPO therapy. The results showed that the level of EPO in non-iron overload group was higher than that in the normal control group (997.44 +/- 473.48 vs 467.27 +/- 238.49, P < 0.05). Obviously, the level of EPO in iron overload group was higher than that in non iron overload group and control group (3257.59 +/- 697.19 vs 997.44 +/- 473.48, P = 0.012, 3257.59 +/- 697.19 vs 467.27 +/- 238.49, P = 0.002). Otherwise, the incidence of EPO resistance in iron overload group was higher than that in non iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was positively related to each other in iron overload group (r = 0.310,P = 0.036). After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in iron overload group were significantly lower than that before therapy (3942.38 +/ 641.82 vs 2266.35 +/- 367.31, P = 0.028;48.61 +/- 10.65 vs 28.52 +/- 12.61, P = 0.034;59.84 +/- 12.62 vs 33.76 +/- 15.43, P = 0.045;3808.01 +/- 750.22 vs 1954.78 +/- 473.18, P = 0.042). Moreover, the level of Hb increased (35 +/- 18 vs 57 +/- 21, P = 0.046) and the EPO resistance in some patients was decreased. It is concluded that iron chelation therapy can improve the efficacy of EPO to alleviate EPO resistance in patients wtih anemic MDS, decrease the pathological level of EPO, enhance Hb levels and reduce the dependency on blood transfusion. PMID- 25130824 TI - [Expressive changes of CD4(+)T cell subset transcription factors in patients with aplastic anemia, myelodysplastic syndrome and acute myeloid leukemia and their clinical significances]. AB - This study was aimed to compare the expressions of specific transcription factors of CD4(+) T cell subset ( T-bet, GATA-3, RORgammat and FoxP3 mRNA) in peripheral blood of patients with aplastic anemia(AA), myelodysplastic syndrome(MDS), and acute myeloid leukemia(AML), and investigate their immune status and pathogenesis, so as to provide experimental basis for the choice of clinical treatment. The expression of T-box (T-bet), GATA-3, ROR-gammat and Foxp3 mRNA in PBMNC were examined by RT-PCR in 42 cases of MDS, including 22 refractory anemia(MDS-RA) and 20 refractory anemia with excess blasts (MDS-RAEB), in 23 cases of AA, 17 cases of AML patients and 16 healthy volunteers respectively. The results indicated that, compared with normal control group, expressions of T-bet and RORgammat mRNA in AA patient group were significantly higher (P < 0.01), expression levels of GATA3 Foxp3 mRNA were lower (both P < 0.01). There was no significant difference in expression of T-bet and GATA3 mRNA between MDS group and normal control group, but the expression levels of Foxp3 and RORgammat mRNA were higher than those in normal controls (P < 0.05); T-bet and RORgammat in MDS RA group were higher than those in the normal controls(P < 0.01), and GATA3 expression significantly reduced (P < 0.05), however, there was no significant difference in expression of Foxp3 between MDS-RA and the controls. Expression levels of T-bet and RORgammat mRNA in patients with MDS-RAEB and AML were lower than those in normal controls (P < 0.05), but the expression levels of GATA3 and Foxp3 mRNA were significantly higher than those in normal controls (P < 0.01). It is concluded that the transcription factor expressions are different in PBMNC of patients among these three diseases. Immune-mediated excessive apoptosis may play an important role in pathogenesis, bone marrow failure in patients with AA and MDS-RA, and abnormal clones of immature cells may be one of main reasons for bone marrow failure in AML and late stage of MDS. PMID- 25130825 TI - [Abnormal quantity of regulatory T cells in peripheral blood of patients with severe aplastic anemia and its clinical significance]. AB - This study was purposed to investigate the role of regulatory T cells (Treg) in the immune unbalance for patients with acquired severe aplastic anemia (SAA). The flow cytometry was used to detect the quantity of CD4(+) CD25(+) CD127(dim) Tregs, T cell subset (CD4(+)/CD8(+) ratio), dendritic cell(DC) subset(mDC/pDC ratio) in 44 SAA patients(25 untreated patients and 19 recovery patients) and 23 normal controls. The correlation between Tregs and T cell subset, DC subset and hemogram were analyzed. The results showed that the percentage of CD4(+) CD25(+) CD127(dim) Tregs in peripheral blood lymphocyte(PBL) of untreated patients was (0.83 +/- 0.44) %, which was obviously lower than that in recovery patients (2.91 +/- 1.24)% and normal controls (2.18 +/- 0.55)% (P < 0.05), but the difference was not statistically significant between latter two groups. The ratio of CD4(+)/CD8(+) was (0.5 +/- 0.3) in untreated patients, which was obviously lower than that in recovery patients (1.2 +/- 0.4) and normal controls (1.11 +/- 0.24) (P < 0.05). The ratio of mDC/pDC was (3.08 +/- 0.72) in untreated patients, which was significantly higher than that in recovery patients(1.61 +/- 0.49) and normal controls (1.39 +/- 0.36) (P < 0.05). The percentage of CD4(+) CD25(+)CD127(dim) Tregs in PBL positively correlated with CD4(+)/CD8(+) ratio (r = 0.695, P < 0.01), and that negatively correlated with mDC/pDC ratio (r = -0.796, P < 0.01). There were significant positive correlations between CD4(+)CD25(+)CD127(dim) Tregs/PBL and WBC, Ret% (r = 0.761, 0.749 respectively, P < 0.01). It is concluded that the decrease of CD4(+)CD25(+)CD127(dim) Tregs quantity in SAA may be one of mechanisms underlying bone marrow failure resulting from the deterioration of immune tolerance and hyperfunction of T-cells. PMID- 25130826 TI - [Safety and effectiveness of tumor-ablative chemotherapy combined with low intensity modified conditioning regimen for 30 patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation]. AB - This study was aimed to investigate the safety and effectiveness of tumor ablative Chemotherapy combined with low intensity conditioning regiment BUCy/TBICy for patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 30 patients with hematologic malignancies received above-mentioned therapeutic method from January 2012 to January 2013 was analyzed retrospectively, and the engraftment, GVHD, infection, conditioning-related toxicity, relapse and survival rates were evaluated. All the patients signed the informed consent before transplantation. The median follow-up duration was 20.5 (16.3-27.3) months. The results indicated that all the patients had been engrafted successfully. One year overall survival (OS) and disease-free survival (DFS) rates were 93.3% and 83.3% respectively. No conditioning-related toxicity occurred. The incidences of II-IV grade aGVHD was 37.9%, among which incidence of III-IV grade aGVHD was 3.4%; incidence of extensive cGVHD was 13.8%. So far, 1 case relapsed, 1 case displayed graft rejection, and poor function of graft occurred in 1 case, death occurred in 2 cases(6.7%). It is concluded that tumor-ablative chemotherapy combined with low intensity-modified BUCy/TBICy is safe and effective in allogeneic hematopoietic stem cell transplantation for hematologic malignancies, and it is useful to reduce relapse of hematologic malignancies after transplantation. PMID- 25130827 TI - [Transplantation of umbilical cord mesenchymal stem cells combined with haploidentical hematopoietic stem cells for 36 patients with refractory/relapsed myeloid leukemia]. AB - This study was purposed to analyse the clinical efficacy of transplantation of umbilical cord mesenchymal stem cells (UC-MSC) combined with haploidentical hematopoietic stem cells (haplo-HSCT) for patients with refractory/relapsed myeloid leukemia. The clinical data of 36 patients received transplantation of UC MSC combined with haplo-HSCT from January 2007 to June 2013 were summarized retrospectively, the engraftment, GVHD and 2 years-overall survival (OS) were analysed. The results showed that the median times of neutrophil count>0.50*10(9)/L and platelet count>20*10(9)/L were 12.0 days and 14.0 days, respectively. Grade III to IV aGVHD occurred in 5 out of 36 patients (13.8%). cGVHD occurred in 12 out of 32 patients (37.5%) and extensive cGVHD occurred in 2 patients. Additionally, only 3 patients (8.3%) experienced relapse. The 2-year OS rate of patients was 76.9%. It is concluded that the transplantation of UC-MSC combined with haplo-HSCT has good therapeutic efficacy for patients with refractory/relapsed myeloid leukemia, and may be served as a therapeutic method especially for patients with high risk and without well matched donor. PMID- 25130828 TI - [Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia]. AB - This study was purposed to explore the therapeutic efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) and in patients with juvenile myelomonocytic leukemia (JMML). The clinical data of 3 cases of CMML and 2 cases of JMML underwent allo-HSCT were analysed in term of multiparameter. The results showed that the hematopoietic stem cells in 5 patients grafted successfully. One case of JMML died of pulmonary disease, other 4 cases survive without disease. The analysis found that the disease burden before transplant, chromosome karyotype, acute GVHD II-IV and poor risk cytogenetics all associated with the relapse rate and disease-free survival rate of CMML. The low intensity conditioning regimen was better than myeloablative conditioning regimen. Type of donor and source of stem cells did not statistically and significantly affect OS and RFS. The splenectomy before allo-HSCT as well as spleen size at time of the alloHSCT did not influence on posttransplantation outcome of JMML. However, cord blood HSCT for JMML patients delayed hematologic recovery as compared to that of bone marrow or peripheral blood HSCT. The age, GVHD, HbF level played an important role in leukemia replace. It is concluded that the allogeneic hematopoietic stem cell transplantation is a curative regimen for CMML and JMML, but there also is a serial problems to be resolved. PMID- 25130829 TI - [Effects of myeloid antigen expression on hematopoietic reconstitution and disease prognosis in acute lymphocytic leukemia patients after allogeneic stem cell transplantation]. AB - This study was aimed to investigate the effects of myeloid antigen expression on hematopoietic reconstitution and disease prognosis in acute lymphocytic leukemia patients post-allogeneic stem cell transplantation (allo-HSCT). Clinical data of 20 patients with acute lymphocytic leukemia in Department of Hematology of the First Affiliated Hospital of Xi'an Jiaotong University from 2008 January to 2014 April were retrospectively analyzed, in which 5 cases were with myeloid antigen (My(+) ALL), while 15 patients were without myeloid antigen expression (My(-) ALL). Differences in prognosis and hematopoietic reconstitution post-allo-HSCT were observed in My(+) ALL and My(-) ALL patients. The results showed that the poor platelet engraftment in patients with My(+) ALL was found more than that in My(-)ALL patients. Three My(+) ALL patients experienced skin chronic graft versus host disease (cGVHD) including local in 2 cases and extensive in one case, and 3 My(-) ALL patients developed grade I-II acute GVHD, while five patients of My(-) ALL experienced cGVHD including local in 3 cases, extensive in 2 cases. One and two year overall survival rate of My(+) ALL and My(-) ALL patients was 80% and 85.7%, 53% and 69.8% respectively, one and two year progress-free survival rate was 53.3% and 54.7%, 26% and 27.4%, respectively. And there was no significant statistical difference between two groups (P > 0.05). It is concluded that the myeloid antigen expression may impact the platelet engraftment post transplantation. There is no significant difference between one and two year overall survival rate and progress-free survival rate of My(+) ALL and My(-) ALL patients after allogeneic stem cell transplantation. PMID- 25130830 TI - [Effect of notch signaling pathway on VEGF promoting rat mesenchymal stem cell proliferation]. AB - This study was purposed to investigate the effect of Notch signaling pathway on VEGF promoting the proliferation of rat mesenchymal stem cells (MSC). Rat MSC were cultured in vitro, and the cells in logarithmic growth phase were used for experiments. The inhibitor DAPT was used to block Notch signaling pathway, and the effect of the pathway on VEGF promoting proliferation of MSC was observed. The experiment was divided into 4 groups: control, VEGF, DAPT and VEGF+DAPT. The CCK-8 was used to assay the cells proliferation of each group, while RT-PCR was used to detect the changes of related genes (Notch1, Notch2, Flk-1, Hes-1) at mRNA levels. The results indicated that the cells survival rate MSC in DAPT group and VEGF+DAPT group was low in each time point (24 h, 48 h, 72 h), the cell number decreased, and the cells became rounded. The survival rate of MSC in VEGF group was the highest; the difference of cell survival rate was statistically significant between the groups (P < 0.01); Compared with the control group, the mRNA expression level of Notch1, Notch2 and Flk-1 in VEGF group was raised, while the expression level of Notch1 and Notch2 in DAPT group and VEGF+DAPT group come down, with statistically significant differences (P < 0.05); whereas the mRNA expression level of Hes-1 in VEGF group was down-regulated, but that in DAPT group and VEGF+DAPT group was up-regulated, and the difference was statistically significant (P < 0.05). Flk-1 mRNA level in DAPT group and VEGF+DAPT group was slightly lower, but the difference was not statistically significant (P > 0.05). It is concluded that Notch signaling pathway plays an important role in promoting the proliferation of rat MSC, treated with VEGF, however, the DAPT can weaken this effect. PMID- 25130831 TI - [Effects of salidroside on proliferation of bone marrow mesenchymal stem cells]. AB - This study was aimed to investigate the effect of salidroside on proliferation of bone marrow mesenchymal stem cells (MSC) and their secretion of stem cell factor (SCF). MSC were isolated and amplified in vitro via density gradient centrifugation and adherence screening method. MCS were identified by flow cytometry and osteogenic/adipogenic induction. The effects of salidroside on cell proliferation, cell cycle and the SCF secretion of MSC were detected by flow cytometry. The results showed that the salidroside could induce the proliferation of MSC, peaked at the concentration of 1.5 mg/ml and in a time-dependent manner (in 24 h, 48 h and 72 h). Salidroside at 1.5 mg/ml could more effectively increase the percentage of cells in S and G1/M phase. Co-cultured with salidroside at the concentration of 1.5 mg/ml for 48 h, the SCF and the expression levels of SCF mRNA in co-culture supernatant were both significantly increased (P < 0.01). It is concluded that salidroside in a range of certain concentration can obviously promote the proliferation of MSC and increase the expression and secretion of SCF. PMID- 25130832 TI - [Protective effect of bone marrow mesenchymal stem cell-derived microvesicles on glutamate injured PC12 cells]. AB - This study was aimed to investigate the protective effect of bone mesenchymal stem cell-derived microvesicles (BMMSC-MV) on glutamate injured PC12 cells so as to elucidate the mechanism of the neural damage repair. BMMSC were isolated and purified with density-gradient centrifugation method, BMMSC-MV were harvested from the supernatants of BMMSC by hypothermal ultracentrifugation method. The surface markers of BMMSC reacted against different antibodies were detected by flow cytometry. The morphology features of MV were observed under an electron microscope. Experiment was divided into three groups, one was a control group, and the other two were glutamate-injured group and co-culture group of BMMSC-MV and glutamate-damaged cells respectively. MTT test was used to evaluate the proliferative status of PC12 cells and the AnnexinV-FITC detecting kit and Hoechst33342 were used to detect the apoptosis of PC12 cells in different groups. The results showed that BMMSC isolated from rat bone marrow were highly positive for CD29, CD44 and negative for CD31, CD34 and CD45. The morphology of MV was round and the vesicles were homogenous in size. BMMSC-MV exhibited a protective effect on the excitotoxicity-injured PC12 cells, displaying increase of cell viability, decrease of Annexin-V/PI staining positive and nuclear condensed cells. It is concluded that BMMSC-MV can protect PC12 cells from glutamate induced apoptosis, suggesting that BMMSC-MV may be a potential candidate for treatment of neurological diseases.This study provides the preliminary experimental and theoretical evidence for use of BMMSC-MV in treatment of neural excited damage. PMID- 25130833 TI - [Effect of umbilical cord MSC infusion on the pulmonary infection in haploidentical hematopoietic stem cell transplantation]. AB - This study was purposed to investigate the effect of umbilical cord mesenchymal cells (UC-MSC) infusion on the pulmonary infection in haploidentical hematopoietic stem cell transplantation (hi-HSCT). The infection of 83 patients underwent hi-HSCT was detected and analysed, among them 42 patients received haploidentical hi-HSCT, 41 received hi-HSCT combined with UC-MSC infusion. The results showed that 31 cases (73.81% +/- 6.78%) were infected by cytomegalovirus and 21 cases in patients received hi-HSCT experienced pulmonary infections, including infections of fungal, virus, bacteria, tubercle bacillus, PCP and so on, the incidence rate was (50 +/- 7.72)%; the infection of cytomegalovirus (CMV) was found in 31 cases, the incidence rate was (78.05 +/- 6.46)%. In patients received hi-HSCT combined with UC-MSC, only 15 patients experienced pulmonary infection, the incidence rate was (36.59 +/- 7.52)%, and the infection of cytomegalovirus (CMV) was observed in 32 patients, the incidence rate was (78.05 +/- 6.46)%. There was no obvious statistical difference between two groups(P > 0.05). It is concluded that the UC-MSC infusion not increases the infection rate in hi-HSCT. PMID- 25130834 TI - [Infection status of HBV, HCV and HIV in voluntary blood donors of Chinese Nanjing area during 2010-2013]. AB - This study was purposed to understand the infection of HBV, HCV, HIV among the voluntary blood donors and the epidemic trend in infectious population in Chinese Nanjing area, and to guide the mobilization and recruitment of blood donors. A total of 199777 whole blood samples of voluntary blood donors were tested by ELISA, the nucleic acid technology (NAT) combined detection (HBV-DNA, HCV-RNA, HIV-RNA) was added for detection of the samples with HBsAg,anti-HCV, anti-HIV at least unilateral negative donors from June 10, 2010 to June 9, 2013 years, and these statistic data were analyzed. Every HIV reactive sample(HIV-antibody and/or HIV-RNA) was sent to be confirmed in the Centers for Disease Control and Prevention in Nanjing. The results showed that the voluntary donors' infection rate of HBsAg, anti-HCV, anti-HIV were 0.45%, 0.28%, 0.11% respectively; NAT positive rate was 0.07%, 32 cases were confirmed with anti-HIV positive, in which 30 cases were male (6 cases were repeated blood donors) and 2 cases were female, 3 cases were unconfirmed, in which 2 cases were males and 1 case was female. The statistical analysis demonstrated that the difference of unqualitative rate of HBsAg, anti-HCV, anti-HIV was statistically significant between the first-time and repeated blood donors.It is concluded that the positive rate of anti-HCV and anti-HIV displayed a declining trend year by year in Nanjing voluntary blood donation population from June 10,2010 to June 9, 2013 years. The unqualitative rate of HBsAg and NAT increased with the age increasing, while that of anti-HCV, anti-HIV decreased with age increasing. The unqualitative rate of the repeated blood donors is far lower than that of the first-time blood donors. The ELISA positive rate of anti-HIV testing in females is higher than that in males, but the confirmed positive rate of male is significantly higher than that of female. Therefore the consulting skills before donating should be improved, concerning the link of recruiting donors, focusing on strengthening the first-time donors' consultation, evaluating and developing the fixed voluntary blood donors, and vigorously popularizing NAT technology in blood screening to improve the blood safety effectively. PMID- 25130836 TI - [Holstein-Friesian RBC as human blood substitute]. AB - alpha-Gal, the main xenotransplantation antigen, can lead to hyperacute rejection (HAR) in xenotransplantation. This study was purposed to investigate the effect of recombinant alpha-galactosidase (alpha-Gal antigen) on the Holstein-Friesian(H F) red blood cells (RBC). The enzymelysis method was used to digest the alpha-Gal antigen on H-F RBC; the saline and anti-human globulin methods were used to perform the agglutination test of H-F RBC and human plasma; the flow cytometry was used to detect the alpha-Gal antigen on surface of H-F RBC, fluorescence intensity of FITC-IB4 and FITC-IgG labeled RBC. The results indicated that the saline and anti-human globulin method showed alpha-galactosidase-treated H-F RBC fail to agglutinate with human pooled plasma; the flow cytometry showed the fluorescence intensity of FITC-IB4 and FITC-IgG labeled RBC decrease 99.0% and 87.8%, respectively. It is concluded that the novel alpha-galactosidase can be used to cleared the alpha-Gal antigen on the surface of H-F RBC and alpha galactosidase-treated H-F RBC may be considered as human blood substitute. PMID- 25130835 TI - [Clinical application of blood matching with hemolytic test in vitro for transfusion treatment of crisis puerpera with acute hemolytic anemia]. AB - This study was aimed to establish the matching method of hemolytic test in vitro, and to guide the transfusion treatment for puerpera with acute hemolytic disease. The donor's erythrocytes were sensibilized by all the antibodies in plasma of patient in vitro and were added with complement, after incubation for 6.5 hours at 38 degrees C, the hemolysis or no hemolysis were observed. It is safe to transfuse if the hemolysis did not occur. The results showed that when the matching difficulty happened to puerpera with acute hemolytic disease, the compatible donor could be screened by hemolytic test in vitro. There were no untoward effects after transfusion of 6 U leukocyte-depleted erythrocyte suspension. The all hemoglobin, total bilirubins, indirect bilirubin, reticulocyte, D-dimex and so on were rapidly improved in patient after transfusion , showing obvious clinical efficacy of treatment. It is concluded that when the matching results can not judge accurately compatible or incompatible through the routine method of cross matching, the agglutinated and no-hemolytic erythrocytes can be screened by hemolytic test in vitro and can be transfused with good efficacy; the hemoglobin level can be promoted rapidly, and no untoward effects occur. PMID- 25130837 TI - [Comparative analysis of collecting mononuclear cells from peripheral blood by using Fenwal CS-3000 plus, haemonetics MCS plus and COBE spectra separators]. AB - This study was aimed to compare the collection efficiency of mononuclear cells (MNC) from peripheral blood as well as the changes of blood-related indices in patient by using 3 cell separators. MNC were collected from 94 tumor patients by using Fenwal CS-3000plus, Haemonetics MCSplus and COBE spectra separators. Routine blood test was performed before and after MNC collection to detect the potential effects of cell separators on blood-related indices in the patients. MNC count was performed. The percentages of CD3(+), CD4(+) and CD8(+) in peripheral blood cells were determined. The results showed that the MNC counts were (3.08 +/- 0.79)*10(9), (3.21 +/- 1.12)*10(9), and (3.22 +/- 1.84)*10(9) per bag by CS-3000plus, MCSplus and COBE spectra, respectively. And the corresponding decrease of platelet percentage was (6.86 +/- 5.70)%, (8.05 +/- 5.14)% and (5.89 +/- 4.48)%, respectively. The CD3, CD4 and CD8 ratios in peripheral blood of patients before and after treatment were significantly statistical different (P < 0.001). It is concluded that the MNC collection can be performed successfully with CS-3000plus, MCSplus and COBE spectra, and their collections can meet the needs in clinic. PMID- 25130838 TI - [Analysis of clinical, iconographical and pathological characteristics, prognosis and treatment methods for 35 cases of Langerhans cell histiocytosis]. AB - Purpose of this study was to analyse the characteristics of clinical, iconographical, pathological and treatment methods of Langerhans cell histiocytosis (LCH), so as to improve the diagnosis and treatment level of this disease. The clinical data of 35 LCH patients were studied retrospectively. These patients were divided into 2 groups according to age <14 years old and >= 14 years old. The clinical symptoms were analysed and the signs, imageology and pathology manifestation and treatment results were evaluated. The results showed that LCH clinical manifestations were diverse and complex. Surgical treatment for patients with single system involvement of LCH was better than that of multi system involvement of LCH (MS-LCH). For the latter, combined chemotherapy effects was better. After 3-year follow-up, 1-year OS was 94% +/- 4%, 2-years OS was 91% +/- 5%, 3-year OS was 86% +/- 7%. 3 years OS of group <14 years old and >= 14 years old was 94% +/- 6% and 81% +/- 10% respectively. The OS of former was better than that of the later, but because a small number of cases, this difference was not statistically significant. It is concluded that LCH is easy to be misdiagnosed, the pathological biopsy is the gold standard of LCH diagnosis. The PET-CT can be of great help in identifying stages and finding lesion areas of the disease. Pulmonary Langerhans cell histiocytosis (PLCH) is more common in adult. Combined chemotherapy can improve the prognosis of the patients. The treatment methods should be choosed according to the stage and classification of disease. PMID- 25130839 TI - [Effect of different irradiation doses on the establishment of murine cGVHD model after MHC matched spleen stem cell transplantation]. AB - This study was aimed to investigate the effect of different irradiation doses on the establishment of murine cGVHD model after MHC matched spleen stem cell transplantation. The male mouse BALB/c(H)-2d was totally irradiated with different radiation dose of (60)Co (TBI), then was infused with the same number of splenocytes from MHC matched DBA/2 male mice. After transplantation, the bodyweight, general appearance, hair changes, survival time and pathological damage were observed. The results indicated that compared to the control group (0 Gy) and the 7.0 Gy group, the mice irradiated with 7.5 Gy and 8.0 Gy showed cGVHD symptoms and obvious pathological damage. At the end of experiments (60 d after transplantation), all mice irradiated by 7.5 Gy survived while only 60% animals survived in the 8.0 Gy group. It is concluded that under infusion of 10(8) MHC matched splenocytes per mouse, 7.5 Gy irradiation is appropriate to efficiently establish cGVHD model. This study laid an important foundation for further studying the pathogenesis, biological characteristics, and intervention factors of cGVHD. PMID- 25130840 TI - [Leukemia stem cells and their targeted clearance]. AB - Leukemia stem cells(LSC) are the root causes of the leukemia, and are also the main reason for the leukemia relapse. Researchers hope that there are some methods to specifically mark the LSC and to clear them for promoting the advancements in the treatment of leukemia. This review discusses the biological characteristics of LSC and its microenvironment, the current internationally recognized main methods for specific marking of LSC, including marking LSC self renewal, apoptosis signaling pathways, microenvironment, cell cycle-related signaling pathways and LSC-specific immune phenotype, so as to eliminate LSC and minimal residual disease through these marking ways. But, at present, there are no specific methods to remove leukaemia stem cells independently, possibly the combination of LSC immune phenotype with blocking the microenvironment signaling pathways can target at and remove LSC, thus improving the prognosis of leukemia. PMID- 25130841 TI - [Mechanisms of aging and programmed death of erythrocytes]. AB - Erythrocytes lack nuclei and mitochondria, critical elements in the machinery of nucleated cell apoptosis. However, most recently, it became obvious that erythrocytes may undergo programmed aging, as well as suicidal death. The term eryptosis has been coined to describe the suicidal erythrocyte death. Eryptosis is triggered mainly by increased cytosolic Ca(2+) activity, in turn, Ca(2+) activates Ca(2+)-sensitive K(+) channels, scramblase, calpain and other proteases, respectively. A series of molecular events of erythrocyte programmed death induced. The cascade reaction of related molecules and finally lead to cell clearance. There is evidence suggesting that erythrocytes aging and death process are regulated tightly and there are many molecular participants and signaling pathways involved in aging and death process of erythrocytes. Erythrocytes have already been used as a model for aging study, and the knowledge about mechanisms involved in eryptosis may provide an important clue to understand the mechanisms involved in suicidal death of nucleated cells. In this review the factors influencing programmed death of erythrocytes, the role of Ca(2+) and ceramide in programmed death of erythrocytes, the role of blebbing in process of erythrocyte aging, the antigens of erythrocyte aging and so on are summarized. PMID- 25130842 TI - [Autophagy and hematologic malignancies]. AB - Autophagy is a major topic of discussion in recent years, and is a physiological process of eukaryotic cells under metabolic stress as hunger, hypoxia, and drug treatment to gain energy by its degradation, and is closely related to the pathogenesis and progression of hematologic malignancies. At present, the results of study on the relationship between autophagy and hematologic malignancies has been found to be indistinct and contradictory. The appropriate treatment should inhibit the growth of tumor cells selectively and meanwhile have no damage to normal cells. So how to choose the target strategies plays an important role in the autophagy related treatment for hematologic malignancies. This article summarizes the occurrence and development of autophagy, the relationship between autophagy and hematologic malignancies, as well as the possible mechanism of autophagy in hematologic malignancies. PMID- 25130843 TI - [Roles of osteoblasts in hematopoietic stem cell niche and relationship between osteoblasts and hematopoietic diseases]. AB - Hemopoietic stem cells(HSCs) are regulated by two niches: osteoblastic niche and vascular niche. Osteoblasts are the critical constitutive regulators of the osteoblastic niche. The significance of osteoblasts for hematopoietic disease has not escaped attention. This review attempts to capture the discoveries of the last few years regarding the role of osteoblasts in hematopoietic stem cell niche and relationship between osteoblasts and hematopoietic diseases. PMID- 25130844 TI - [Clinical translational research of chimeric antigen receptor-T (CAR-T) cells for the treatment of relapsed and refractory B-cell lymphoma/leukemia]. AB - B-cell lymphoma and leukemia are the most common subtypes of malignant lymphomas. Relapse and refractory to multiple therapy are the main reasons of treatment failure. As the classical anti-tumor methods, surgery, radiation, chemotherapy and palliative therapy have cured lots of cancer patients. However, each year many patients still died of different kinds of hard-to-treat cancers. Although the ratio of complete remission of B-cell lymphoma/leukemia patients particularly with CD20 positive mature B cell malignancies has been largely increased after the application of Rituximab in clinic, nearly 20%-40% patients still died due to relapse and refractory to the treatment. During last five years, the development of chimeric antigen receptor-T (CAR-T) cells, especially CD19 CAR-T cells, which can recognize CD19 specifically expressed on B cells and have been demonstrated to be significantly effective to relapsed and refractory B cell lymphoma/leukemia in clinical trials, has gradually attracted extensively concerning from researchers and clinicians. Many medical institutions all over the world (besides in China) have registered the clinical trials for B-cell lymphoma/leukemia patients by use of CAR-T cells. In this review, we summarize the developmental history, the main ongoing clinical trials and proved potential adverse affects of CD19 CAR-T cells for the treatment of patients with B-cell lymphoma/leukemia. PMID- 25130846 TI - [Dendritic cells and acute myeloid leukemia]. AB - Dendritic cells can be derived from leukemia cells and normal precursor cells in the patients with acute myeloid leukemia (AML). Dendritic cells may capture leukemia antigen in bone marrow or lymph nodes, and present leukemia common antigen to stimulate proliferation of specific CD8(+) T cells, playing anti leukemia effect. Dendritic cells for clinical and experimental use are transformed from leukemia cells and peripheral blood mononuclear cells and loaded in vitro with leukemia -specific or tumor common antigen, play a therapeutic role after reinfusion. This article reviews dendritic cells in the immunotherapy of AML. PMID- 25130847 TI - [Research advances on microchimerism]. AB - The microchimerism is a status of the microcell or DNA of an individual in another one with genetic differences. Taking an overall view about the discovery and research of the microchimerism, it was found that although the study of the microchimerism emphasizes the formation, origin, distribution, type, relationship to disease and several other aspects, the objects of the study are always the microchimerism that obtained naturally. As it is known to all, the microchimerism can also be produced in some clinical treatment, such as in the transplant and transfusion, but compared with the microchimerism gained naturally, obviously, the study for the iatrogenic microchimerism formed in the treatment is not elaborate enough. The curative effect of micro transplantation, a new technique for leukemia treatment, is obvious, but its mechanism is unclear, whether that is related to microchimerism still needs further research. This review summarizes the study history and perspective of the microchimerism so as to provide some ideas for studying the action mechanism of microchimerism in micro transplantation. PMID- 25130845 TI - [Research advances on ADAM28 expression and ADAM28-mediated tumor metastasis]. AB - A disintegrin-metalloproteinase 28 (ADAM28) is one of important members of ADAM family, that is involved in various biological events including cell adhesion, proteolysis, growth and metastasis of solid tumors and hematological malignancies. Studies have shown that ADAM28 is highly expressed in several human tumors, such as lung, breast and bladder cancers, and chronic lymphocytic leukemia, and its tissue expression levels correlate with cancer metastasis. ADAM28-mediated cancer cell metastasis may be related with the cleavage of von Willebrand's factor (vWF), insulin-like growth factor binding protein-3 (IGFBP-3) and connective tissue growth factor (CTGF), as well as the promoting PSGL-1/P selectin-mediated cell adhesion. This review summarizes the basic and translational aspects of ADAM28 biology that might stimulate the interest in ADAM28 research and discovery of novel ADAM28 targets, providing potential novel therapies for metastatic cancers. PMID- 25130848 TI - [Structure and function of ADAMTS13 protease and its relation with diagnosis and treatment of TTP]. AB - ADAMTS13, a plasma metalloprotease, specifically cleaves von Willebrand factor (vWF). Severe deficiency of plasma ADAMTS13 activity results in thrombotic thrombocytopenic purpura (TTP). In this review, the structure and function of ADAMTS13 protease and its relationship with TTP are summarized. PMID- 25130849 TI - [Research advances in the pathogenesis, diagnosis and treatment of hemophagocytic lymphohistiocytosis in children]. AB - Hemophagocytic lymphohistiocytosis (HLH), or hemophagocytic syndrome (HPS), is characterized clinically by abrupt onset and progressive deterioration and even death. HLH is much more prevalent in children, and is potentially fatal if early diagnosis is not made and appropriate HLH-directed therapy not instituted. Increasing genetic defects and underlying diseases or causative factors have been identified to be closely implicated in the pathogenesis of HLH. In addition, great advances have been made in the past few years in terms of HLH diagnosis and clinical management. In the present review, the cause of disease, contemporary classification, epidemiology, genetic defects and molecular mechanisms, updated diagnostic criteria and novel treatment strategies for childhood HLH are summarized. PMID- 25130850 TI - [Research advances on roles of ADAMTS-13 in thrombotic diseases]. AB - ADAMTS-13 is a plasma metalloprotease that cleaves von willebrand factor (vWF).At the present,it has been made great progresses on its structure, biological characteristics and function. ADAMTS-13 plays an important role in artery and venous thrombosis,besides controlling the cleaving of vWF, and the activity of the ADAMTS-13 can be effected by ion concentration and thrombin signal transduction pathway,but how the mechanism of ADAMTS-13 controlled is still not clear. This article reviews ADAMTS-13 changes,relevant mechanism and influencing factors of the enzyme regulation. PMID- 25130851 TI - [Progress of improving blood donor screening by nucleic acid technology]. AB - With increasing application of blood transfusion, the research of side-effects such as transfusion-transmitted infections (TTIs) became more and more important. Up to the 90's of the 20th century, the first blood donor screening for pathogens transfected from blood transfusion entirely depended on serological test. At this time, the detection of virus were performed mainly by using method of detecting antibody, except hepatitis B virus (HBV) can be detected by hepatitis B surface antigen (HBsAg). Now, the molecular technologies, such as the polymerase chain reaction (PCR), have been used in clinic. These technologic methods can provide capability of detection for blood donor screening and reduced possibility of infection from blood transfusion. This review summarises the development of nucleic acid amplification technology and describes its current state. PMID- 25130852 TI - [Recent advances on the prognostic value of immunophenotyping in multiple myeloma by flow cytometry]. AB - Clinical application of flow cytometry in multiple myeloma (MM) can be found in various dimensions, such as in differential diagnosis of malignant plasma cell disorder from reactive plasmacytosis, identification of the progression risk in MM, and in the detection of minimal residual disease. Flow cytometry-based clonality assessment with immuno-phenotyping encourages and enables the most stringent method of diagnosis and follow-up. The objective of this review is to summarize the recent information of the malignant plasma cell phenotypic profile of MM. The most comprehensive antigens, such as CD19, CD27, CD28, CD45, CD56 and CD117, play a significant role in the characterization of normal and malignant plasma cells. This review also focuses on the association of malignant phenotypic markers with chromosomal aberrations that identify the specific prognostic factors in MM. PMID- 25130853 TI - [Role of ASXL1 mutation in myeloid malignancies]. AB - Additional sex comb-like 1 ( ASXL1) is an enhancer of Trithorax and Polycomb family, which are necessary for the maintenance of stable repression of homeotic and other loci. Recently, alterations of ASXL1 gene were identified in the hematopoietic cells from patients with a variety of myeloid malignancies, including chronic myelomonocytic leukemia (CMML, 43% of cases), myelodysplastic syndrome (MDS, 20%), myeloproliferative neoplasms (MPN, 10%) and acute myeloid leukemia (AML, 20%). The majority of ASXL1 mutations are frameshift and nonsense mutations. These clinical data suggest an important role of ASXL1 in the pathogenesis and/or transformation of myeloid malignancies. However, the role of ASXL1 in the pathogenesis of myeloid malignancies and in normal hematopoiesis in vivo, as well as the underlying mechanisms remains unknown. This article reviews the structure and function of ASXL1, the clinical characteristic and prognostic significance of ASXL1 mutation, the association of ASXL1 with other gene mutation, as well as ASXL1 knock-down or silence in vitro and in vivo models. PMID- 25130854 TI - [Research progress on hereditary fibrinogen abnormalities]. AB - As the most abundant component of coagulation system, fibrinogen not only takes part in clotting, but also works as one of acute phase proteins, which participates in many physiological and pathophysiological processes. Studies of fibrinogen abnormalities contribute to understand the molecular basis of disorders of fibrinogen protein function and metabolism, caused mainly by gene mutation, commonly associated with bleeding, thrombophilia, or both. Diseases affecting fibrinogen could be classified to the acquired or inherited disease. In this review, the research progress on the molecular basis, possible action mechanism of the hereditary fibrinogen abnormalities and its clinical research are summarized. PMID- 25130855 TI - Effect of a novel synthesized sulfonamido-based gallate-SZNTC on chondrocytes metabolism in vitro. AB - The ideal therapeutic agent for treatment of osteoarthritis (OA) should have not only potent anti-inflammatory effect but also favorable biological properties to restore cartilage function. Gallic acid (GA) and its derivatives are anti inflammatory agents reported to have an effect on OA (Singh et al., 2003) [1]. However, GA has much weaker antioxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel sulfonamido-based gallate named sodium salt of 3,4,5 trihydroxy-N-[4-(thiazol-2-ylsulfamoyl)-phenyl]-benzamide (SZNTC) and analyzed its chondro-protective and pharmacological effects. Comparison of SZNTC with GA and sulfathiazole sodium (ST-Na) was also performed. Results showed that SZNTC could effectively inhibit the Interleukin-1 (IL-1)-mediated induction of metalloproteinase-1 (MMP-1) and MMP-3 and could induce the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), which demonstrated ability to reduce the progression of OA. SZNTC can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Expression of the collagen I gene was effectively down-regulated, revealing the inhibition of chondrocytes dedifferentiation by SZNTC. Hypertrophy that may lead to chondrocyte ossification was also undetectable in SZNTC groups. The recommended dose of SZNTC ranges from 3.91MUg/ml to 15.64MUg/ml, among which the most profound response was observed with 7.82MUg/ml. In contrast, its source products of GA and ST-Na have a weak effect in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed SZNTC as a promising novel agent in the treatment of chondral and osteochondral lesions. PMID- 25130856 TI - Differential effects of baicalein and its sulfated derivatives in inhibiting proliferation of human breast cancer MCF-7 cells. AB - This study was to investigate the anticancer effects of baicalein (Bai) and its two sulfated derivatives, namely baicalein-7-O-sulfate (BoS) and baicalein-8 sodium sulfonate (BcS). BcS was shown to exhibit stronger growth inhibition against human breast cancer MCF-7 cells, compared with structurally related Bai and BoS, where IC50 values of BoS, Bai and BcS were 97.7, 68.3 and 30.4MUM, respectively. BoS, Bai and BcS were further shown to mediate the cell-cycle arrest principally in G0/G1-phase within 12h of treatment with MCF-7 cells, and after 12h, they arrested principally in S-phase. It was also found that 17.7%, 44.9% and 70.5% of MCF-7 cells entered the early phase of apoptosis when treated with 200MUM BoS, Bai and BcS for 24h, followed by an intracellular ROS generation. BcS displays strong antitumor effect through ROS-dependent apoptosis pathway in MCF-7 cells, and has promising potential to be developed as an antitumor compound. PMID- 25130857 TI - Carbohydrate malabsorption mechanism for tumor formation in rats treated with the SGLT2 inhibitor canagliflozin. AB - Canagliflozin is an SGLT2 inhibitor used for the treatment of type 2 diabetes mellitus. Studies were conducted to investigate the mechanism responsible for renal tubular tumors and pheochromocytomas observed at the high dose in a 2-year carcinogenicity study in rats. At the high dose (100mg/kg) in rats, canagliflozin caused carbohydrate malabsorption evidenced by inhibition of intestinal glucose uptake, decreased intestinal pH and increased urinary calcium excretion. In a 6 month mechanistic study utilization of a glucose-free diet prevented carbohydrate malabsorption and its sequelae, including increased calcium absorption and urinary calcium excretion, and hyperostosis. Cell proliferation in the kidney and adrenal medulla was increased in rats maintained on standard diet and administered canagliflozin (100mg/kg), and in addition an increase in the renal injury biomarker KIM-1 was observed. Increased cell proliferation is considered as a proximal event in carcinogenesis. Effects on cell proliferation, KIM-1 and calcium excretion were inhibited in rats maintained on the glucose-free diet, indicating they are secondary to carbohydrate malabsorption and are not direct effects of canagliflozin. PMID- 25130858 TI - Role of Rho small GTPases in meniscus cells. AB - We previously reported that mechanical stretch regulates Sry-type HMG box (SOX) 9 dependent alpha1(II) collagen (COL2A1) expression in inner meniscus cells. This study examined the role of the small Rho guanosine 5' triphosphatase Rac1 and Rho associated kinase (ROCK) in the regulation of stretch-induced SOX9 gene expression in cultured human inner meniscus cells. COL2A1 and SOX9 gene expression was assessed by real-time PCR after application of uni-axial cyclic tensile strain (CTS) in the presence or absence of ROCK and Rac1 inhibitors. The subcellular localization of SOX9 and the Rac1 effector cyclic AMP response element-binding protein (CREB), the phosphorylation state of SOX9, Rac1 activation, and the binding of CREB to the SOX9 promoter were assessed. CTS increased the expression of COL2A1 and SOX9, which was suppressed by inhibition of Rac1. ROCK inhibition enhanced COL2A1 and SOX9 gene expression in the absence of CTS. CTS stimulated the nuclear translocation and phosphorylation of SOX9, and increased Rac1 activation. CTS also increased the binding of CREB to the SOX9 promoter. The results suggest that mechanical stretch-dependent upregulation of SOX9 by CREB in inner meniscus cells depends on the antagonistic activities of ROCK and Rac1. PMID- 25130860 TI - Activated recombinant factor VIIa should not be used in patients with refractory variceal bleeding: it is mostly ineffective, is expensive, and may rarely cause serious adverse events. PMID- 25130859 TI - Nutritional assessment of amyotrophic lateral sclerosis in routine practice: value of weighing and bioelectrical impedance analysis. AB - INTRODUCTION: We evaluated clinical and bioelectrical impedance (BIA) parameters at the time of diagnosis and during follow-up and associated these parameters with survival in amyotrophic lateral sclerosis (ALS) patients. METHODS: One hundred seventeen patients were enrolled and were evaluated prospectively every 3 months. All patients underwent at least 1 BIA-based assessment, and 73 underwent at least 2 assessments. Data regarding the site of onset, age at onset, weight, body mass index (BMI), amyotrophic lateral sclerosis functional rating scale score (ALSFRS), fat-free mass (FFM), fat mass (FM), and phase angle (PA) were collected. RESULTS: At the time of diagnosis, weight loss exceeding 5% of the premorbid weight and low PA were poor prognostic factors. During follow-up, a decrease of PA and FFM were associated with shorter survival, regardless of weight loss. CONCLUSIONS: These results confirm that BIA is useful to identify poor prognostic factors at the time of diagnosis and during follow-up and thus could be used to monitor patients during follow-up. Early identification of poor prognostic factors enables nutritional management and might improve patient survival. PMID- 25130861 TI - Surgical extrusion of multiple teeth with crown-root fractures: a case report with 18-months follow up. AB - The objective of this case report is to describe the treatment procedure involved in surgical extrusion of multiple crown-root fractures and review the critical factors to be considered for successful and predictable outcome. The treatment of complicated crown-root fracture in anterior teeth is likely to compromise function and aesthetics when approached with conventional surgical crown lengthening. Orthodontic extrusion has also been suggested; however, it is time consuming, aesthetically compromising and hardly applicable on multiple anterior crown-root fractures due to the limited source of anchorage. To overcome the shortcomings of suggested treatment modalities, we performed atraumatic surgical extrusion of four anterior fractured teeth along with their rotation within the sockets. The teeth were gently luxated and extruded to the desired position, minimizing damage to the marginal alveolar bone and root surfaces without rigid splint. The treated teeth were functioning normally 18 months after the procedure, and the mobility and probing depths were within normal limits. Radiographs revealed functional periodontal ligament space along with lamina dura formation around the extruded roots. There was neither root resorption nor significant marginal bone loss. This technique might be a promising alternative to conventional crown lengthening, especially in the anterior zone to avoid functional or aesthetic complications. PMID- 25130863 TI - Relationships between dietary intakes of children and their parents: a cross sectional, secondary analysis of families participating in the Family Diet Quality Study. AB - BACKGROUND: Being overweight and obese in Australian children is common. Current evidence related to parental influence on child dietary intake is conflicting, and is particularly limited in terms of which parent exerts the stronger relationship. The present study aimed to assess mother-father and parent-child dietary relationships and to identify which parent-child relationship is stronger. METHODS: A cross-sectional analysis was performed of dietary intake data from 66 families with one parent and one child aged 8-12 years who were participating in the Family Diet Quality Study, in the Hunter and Forster regions of New South Wales, Australia. Dietary intakes were assessed using adult and child specific, validated semi-quantitative 120-item food frequency questionnaires. Diet quality and variety subscores were assessed using the Australian Recommended Food Scores for adults and children/adolescents. Pearson's correlations were used to assess dietary relationships between mother-father, father-child and mother-child dyads. RESULTS: Weak-to-moderate correlations were found between mother-child dyads for components of dietary intake (r = 0.27 0.47). Similarly, for father-child dyads, predominantly weak-to-moderate correlations were found (r = 0.01-0.52). Variety of fruit intake was the most strongly correlated in both parent-child dyads, with the weakest relationships found for fibre (g 1000 kJ(-1) ) in father-child and percentage energy from total fats for mother-child dyads. Mother-father dyads demonstrated mostly moderate-to strong correlations (r = 0.13-0.73), with scores for condiments showing the weakest relationship and vegetables the strongest. For all dyads, strong correlations were observed for overall diet quality (r = 0.50-0.59). CONCLUSIONS: Parent-child dietary intake is significantly related but differs for mother versus fathers. Further research is required to examine whether differing dietary components should be targeted for mothers versus fathers in interventions aiming to improve family dietary patterns. PMID- 25130864 TI - Sono-assisted extraction of alcohol-insoluble extract from Althaea rosea: purification and chemical analysis. AB - A Box-Behnken design (BBD) was used to evaluate the effects of ultrasonic power, extraction time, extraction temperature, and water to raw material ratio on extraction yield of alcohol-insoluble polysaccharide of Althaea rosea leaf (ARLP). Purification was carried out by dialysis method. Chemical analysis of ARLP revealed contained 12.69 +/- 0.48% moisture, 79.33 +/- 0.51% total sugar, 3.82 +/- 0.21% protein, 11.25 +/- 0.37% uronic acid and 3.77 +/- 0.15% ash. The response surface methodology (RSM) showed that the significant quadratic regression equation with high R(2) (=0.9997) was successfully fitted for extraction yield of ARLP as function of independent variables. The overall optimum region was found to be at the combined level of ultrasonic power 91.85 W, extraction time 29.94 min, extraction temperature 89.78 degrees C, and the ratio of water to raw material 28.77 (mL/g). At this optimum point, extraction yield of ARLP was 19.47 +/- 0.41%. No significant (p>0.05) difference was found between the actual and predicted (19.30 +/- 0.075%) values. The results demonstrated that ARLP had strong scavenging activities on DPPH and hydroxyl radicals. PMID- 25130865 TI - Predictors of cerebral microembolization during phased radiofrequency ablation of atrial fibrillation: role of the ongoing rhythm and the site of energy delivery. AB - BACKGROUND: Pulmonary vein isolation with phased radiofrequency current and use of a pulmonary vein ablation catheter (PVAC) has recently been associated with a high incidence of clinically silent brain infarcts on diffusion-weighted magnetic resonance imaging, and a high microembolic signal (MES) count detected by transcranial Doppler. We investigated the potential effects of the ongoing rhythm and the target vein during energy delivery (ED) on MES generation during PVAC ablations. METHODS AND RESULTS: A total of 735 EDs during 48 PVAC ablations were analyzed. MES counts were recorded for each ED and time-stamped for correlation with the ongoing rhythm and the target vein for each ED. Significantly higher MES counts were observed during ablations of the left-sided as compared with the right-sided pulmonary veins (P = 0.0003). Similarly, higher MES counts were detected during EDs in atrial fibrillation as compared with sinus rhythm when the temperature was >56 degrees C (P < 0.0001). The ongoing rhythm had no effect on the number of MESs at lower temperatures during ablation. CONCLUSIONS: Both the ongoing rhythm during ED and the site of ablation influence microembolus generation during PVAC ablation procedures. PMID- 25130862 TI - Predicting the evolution of spreading on complex networks. AB - Due to the wide applications, spreading processes on complex networks have been intensively studied. However, one of the most fundamental problems has not yet been well addressed: predicting the evolution of spreading based on a given snapshot of the propagation on networks. With this problem solved, one can accelerate or slow down the spreading in advance if the predicted propagation result is narrower or wider than expected. In this paper, we propose an iterative algorithm to estimate the infection probability of the spreading process and then apply it to a mean-field approach to predict the spreading coverage. The validation of the method is performed in both artificial and real networks. The results show that our method is accurate in both infection probability estimation and spreading coverage prediction. PMID- 25130868 TI - Psychopathy and Low Anxiety: Meta-Analytic Evidence for the Absence of Inhibition, Not Affect. AB - Despite historical conviction that the psychopath is low-anxious, contemporary research remains equivocal. An examination of the literature suggests that the lack of consensus may be due to problems with the conceptualization of "psychopathic low anxiety." It was hypothesized that ambiguous relations could be clarified by parsing the psychopathic low anxiety construct into more discrete components: anxiety, fear, and constraint. The current study examined the relations between psychopathy and these three different low anxiety conceptualizations through three meta-analyses. Results indicated that anxiety and fear were negligibly related to psychopathy Total. In contrast, constraint demonstrated a medium negative relation with psychopathy Total. Relations showed divergence across psychopathy factor scores. Anxiety, fear, and constraint were all negatively related to Factor 1 scores, whereas anxiety was positively related, and constraint negatively related, to Factor 2 scores. These meta analytic findings suggest that although psychopathic individuals have deficits in inhibition/constraint, they do not necessarily exhibit a consistent absence of negative affect. This interpretation is consistent with predictions regarding the personality correlates of the factors of psychopathy, indicating that while constraint composes a large part of psychopathy assessments, it is less clear how much anxiety lends to the construct. PMID- 25130866 TI - Prevalence and correlates of treatment failure among Kenyan children hospitalised with severe community-acquired pneumonia: a prospective study of the clinical effectiveness of WHO pneumonia case management guidelines. AB - OBJECTIVE: To determine the extent and pattern of treatment failure (TF) among children hospitalised with community-acquired pneumonia at a large tertiary hospital in Kenya. METHODS: We followed up children aged 2-59 months with WHO defined severe pneumonia (SP) and very severe pneumonia (VSP) for up to 5 days for TF using two definitions: (i) documentation of pre-defined clinical signs resulting in change of treatment (ii) primary clinician's decision to change treatment with or without documentation of the same pre-defined clinical signs. RESULTS: We enrolled 385 children. The risk of TF varied between 1.8% (95% CI 0.4 5.1) and 12.4% (95% CI 7.9-18.4) for SP and 21.4% (95% CI 15.9-27) and 39.3% (95% CI 32.5-46.4) for VSP depending on the definition applied. Higher rates were associated with early changes in therapy by clinician in the absence of an obvious clinical rationale. Non-adherence to treatment guidelines was observed for 70/169 (41.4%) and 67/201 (33.3%) of children with SP and VSP, respectively. Among children with SP, adherence to treatment guidelines was associated with the presence of wheeze on initial assessment (P = 0.02), while clinician non adherence to guideline-recommended treatments for VSP tended to occur in children with altered consciousness (P < 0.001). Using propensity score matching to account for imbalance in the distribution of baseline clinical characteristics among children with VSP revealed no difference in TF between those treated with the guideline-recommended regimen vs. more costly broad-spectrum alternatives [risk difference 0.37 (95% CI -0.84 to 0.51)]. CONCLUSION: Before revising current pneumonia case management guidelines, standardised definitions of TF and appropriate studies of treatment effectiveness of alternative regimens are required. PMID- 25130867 TI - Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome. AB - Mutations in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases are associated with a range of clinical phenotypes. Here, we report a novel disorder in three adult patients with a phenotype including cataracts, short-stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy, and skeletal dysplasia. Using SNP genotyping and whole-exome sequencing, we identified a single likely causal variant, a missense mutation in a conserved residue of the nuclear gene IARS2, encoding mitochondrial isoleucyl tRNA synthetase. The mutation is homozygous in the affected patients, heterozygous in carriers, and absent in control chromosomes. IARS2 protein level was reduced in skin cells cultured from one of the patients, consistent with a pathogenic effect of the mutation. Compound heterozygous mutations in IARS2 were independently identified in a previously unreported patient with a more severe mitochondrial phenotype diagnosed as Leigh syndrome. This is the first report of clinical findings associated with IARS2 mutations. PMID- 25130869 TI - Wasted, overdosed, or beyond saving--to act or not to act? Heroin users' views, assessments, and responses to witnessed overdoses in Malmo, Sweden. AB - BACKGROUND: Overdose is a significant cause of death among heroin users. Frequently, other heroin users are present when an overdose occurs, which means the victim's life could be saved. There is a lack of studies that, based on heroin users own stories, examine their views, assessments, and responses to witnessed overdoses. METHODS: The study is based on qualitative interviews with thirty-five heroin users who witnessed someone else's overdose. RESULTS: The heroin users generally had a positive attitude towards assisting peers who had overdosed. A number of factors and circumstances, however, contribute to witnesses often experiencing resistance to or ambivalence about responding. The witness's own high, the difficulty in assessing the seriousness of the situation, an unwillingness to disturb someone else's high, uncertainty about the motive behind the overdose and whether the victim does or does not want assistance as well as fear of police involvement, were common factors that acted as barriers to adequate responses in overdose situations. CONCLUSION: The fact that being high makes it difficult to respond to overdoses, using traditional methods, argues for simpler and more effective response techniques. This can include intranasal naloxone programs for heroin users. The findings regarding the uncertainty about the intention of the overdose victim and the sensitivity to the experience of a good high argue for more up-front communication and discussion amongst using peers so that they can make their intentions clear to each other. Issues like this can be addressed in overdose education interventions. Overdose prevention measures also need to address the fact that fear of the police acts as a barrier to call emergency services. PMID- 25130870 TI - N-heterocyclic carbene catalyzed formal [3+2] annulation reaction of enals: an efficient enantioselective access to spiro-heterocycles. AB - A highly enantioselective N-heterocyclic carbene (NHC) catalyzed formal [3+2] annulation of alpha,beta-unsaturated aldehydes with azaaurones or aurone generating spiro-heterocycles has been developed. The protocol represents a unique NHC-activation-based approach to access spiro-heterocyclic derivatives bearing a quaternary stereogenic center with high optical purity (up to 95% ee). PMID- 25130872 TI - Structure, stability, and IgE binding of the peach allergen Peamaclein (Pru p 7). AB - Knowledge of the structural properties of allergenic proteins is a necessary prerequisite to better understand the molecular bases of their action, and also to design targeted structural/functional modifications. Peamaclein is a recently identified 7 kDa peach allergen that has been associated with severe allergic reactions in sensitive subjects. This protein represents the first component of a new allergen family, which has no 3D structure available yet. Here, we report the first experimental data on the 3D-structure of Peamaclein. Almost 75% of the backbone resonances, including two helical stretches in the N-terminal region, and four out of six cysteine pairs have been assigned by 2D-NMR using a natural protein sample. Simulated gastrointestinal digestion experiments have highlighted that Peamaclein is even more resistant to digestion than the peach major allergen Pru p 3. Only the heat-denatured protein becomes sensitive to intestinal proteases. Similar to Pru p 3, Peamaclein keeps its native 3D-structure up to 90 degrees C, but it becomes unfolded at temperatures of 100-120 degrees C. Heat denaturation affects the immunological properties of both peach allergens, which lose at least partially their IgE-binding epitopes. In conclusion, the data collected in this study provide a first set of information on the molecular properties of Peamaclein. Future studies could lead to the possible use of the denatured form of this protein as a vaccine, and of the inclusion of cooked peach in the diet of subjects allergic to Peamaclein. PMID- 25130873 TI - Retinoic acid signaling in cancer: The parable of acute promyelocytic leukemia. AB - Inevitably fatal some 40 years, acute promyelocytic leukemia (APL) can now be cured in more than 95% of cases. This clinical success story is tightly linked to tremendous progress in our understanding of retinoic acid (RA) signaling. The discovery of retinoic acid receptor alpha (RARA) was followed by the cloning of the chromosomal translocations driving APL, all of which involve RARA. Since then, new findings on the biology of nuclear receptors have progressively enlightened the basis for the clinical efficacy of RA in APL. Reciprocally, the disease offered a range of angles to approach the cellular and molecular mechanisms of RA action. This virtuous circle contributed to make APL one of the best-understood cancers from both clinical and biological standpoints. Yet, some important questions remain unanswered including how lessons learnt from RA triggered APL cure can help design new therapies for other malignancies. PMID- 25130871 TI - The chicken model of spontaneous ovarian cancer. AB - The chicken is a unique experimental model for studying the spontaneous onset and progression of ovarian cancer (OVC). The prevalence of OVC in chickens can range from 5 to 35% depending on age, genetic strain, reproductive history, and diet. Furthermore, the chicken presents epidemiological, morphological, and molecular traits that are similar to human OVC making it a relevant experimental model for translation research. Similarities to humans include associated increased risk of OVC with the number of ovulations, common histopathological subtypes including high-grade serous, and molecular-level markers or pathways such as CA-125 expression and p53 mutation frequency. Collectively, the similarities between chicken and human OVC combined with a tightly controlled genetic background and predictable onset window provides an outstanding experimental model for studying the early events and progression of spontaneous OVC tumors under controlled environmental conditions. This review will cover the existing literature on OVC in the chicken and highlight potential opportunities for further exploitation (e.g. biomarkers, prevention, treatment, and genomics). PMID- 25130875 TI - Abstracts of the 70th Congress of the Italian Society of Pediatrics, June 11-14, 2014, Palermo, Italy. PMID- 25130874 TI - Impact of VEGFA -583C > T polymorphism on serum VEGF levels and the susceptibility to acute chest syndrome in pediatric patients with sickle cell disease. AB - We investigated the association of VEGFA -583C > T on VEGF serum levels and acute chest syndrome (ACS) in 351 pediatric patients with sickle cell disease (SCD), of whom 90 had ACS, and 261 were ACS-free controls. Significant differences in -583C > T minor allele and genotype frequencies were seen between ACS cases and controls, evidenced by enrichment of -583T/T genotypes in patients with ACS, which were linked with reduction in VEGF serum levels. VEGFA -583C > T and reduced VEGF serum levels may influence ACS risk in patients with SCD, which will aid in identifying patients with SCD who are at high risk of ACS. PMID- 25130876 TI - Incidence and risk factors of poor mobilization in adult autologous peripheral blood stem cell transplantation: a single-centre experience. AB - BACKGROUND AND OBJECTIVES: Collection of sufficient CD34+ cells for autologous peripheral blood stem cell (PBSC) transplantation is frequently failed in patients with lymphoma or multiple myeloma (MM). We investigated the incidence and the predictive factors for poor mobilization. MATERIALS AND METHODS: A total of 205 adult patients (101 lymphoma and 104 MM) were retrospectively included for identifying the incidence of mobilization failure and the predictive factors for poor mobilization in conventional G-CSF-based mobilization regimen. Another 17 patients who used plerixafor for mobilization were included. RESULTS: Overall, 14.1% of patients (21.8% of patients with lymphoma, 6.7% of patients with MM) were poor mobilizers. Univariate analysis and multivariate analysis revealed an interval from G-CSF administration to PBSC collection exceeding 10 days and peripheral blood mononuclear cells count on the first day of collection were predictive factors for poor mobilization in lymphoma, but not in MM. Among plerixafor-treated patient group, 9 of 11 poor mobilizers who received second cycle plerixafor mobilization were able to collect higher number of CD34+ cells than that of CD34+ cells during the G-CSF-based first mobilization. All patients who had received initial plerixafor mobilization reached 2.0 * 10(6) CD34+ cells/kg during the four leukaphereses. CONCLUSION: In conventional G-CSF-based mobilization, early PBSC collection after G-CSF administration might enhance CD34+ cell yield. A combination of a new mobilizing agent, plerixafor, would be helpful to harvest sufficient number of CD34+ cells for successful transplantation outcome while reducing the effort of collection procedures in poor mobilizers. PMID- 25130878 TI - Surface charge effects on optical trapping of nanometer-sized lipid vesicles. AB - Optical trapping of nanometer-sized lipid vesicles has been challenging due to the low refractive index contrast of the thin lipid bilayer to the aqueous medium. Using an "optical bottle", a recently developed technique to measure interactions of nanoparticles trapped by an infrared laser, we report, for the first time, quantitative measurements of the trapping energy of charged lipid vesicles. We found that the trapping energy increases with the relative amount of anionic lipids (DOPG) to neutral lipids (DOPC) in vesicles. Moreover, as monovalent salt is added into the exterior solution of vesicles, the trapping energy rapidly approaches zero, and this decrease in trapping energy strongly depends on the amount of anionic lipids in vesicles. A simple model with our experimental observations explains that the trapping energy of charged lipid vesicles is highly correlated with the surface charge density and electric double layer. In addition, we demonstrated selective trapping of a binary mixture of vesicles in different mole fractions of charged lipids, a strategy that has potential implications on charge selective vesicle sorting for engineering applications. PMID- 25130879 TI - Biomarker driven population enrichment for adaptive oncology trials with time to event endpoints. AB - The development of molecularly targeted therapies for certain types of cancers has led to the consideration of population enrichment designs that explicitly factor in the possibility that the experimental compound might differentially benefit different biomarker subgroups. In such designs, enrollment would initially be open to a broad patient population with the option to restrict future enrollment, following an interim analysis, to only those biomarker subgroups that appeared to be benefiting from the experimental therapy. While this strategy could greatly improve the chances of success for the trial, it poses several statistical and logistical design challenges. Because late-stage oncology trials are typically event driven, one faces a complex trade-off between power, sample size, number of events, and study duration. This trade-off is further compounded by the importance of maintaining statistical independence of the data before and after the interim analysis and of optimizing the timing of the interim analysis. This paper presents statistical methodology that ensures strong control of type 1 error for such population enrichment designs, based on generalizations of the conditional error rate approach. The special difficulties encountered with time-to-event endpoints are addressed by our methods. The crucial role of simulation for guiding the choice of design parameters is emphasized. Although motivated by oncology, the methods are applicable as well to population enrichment designs in other therapeutic areas. PMID- 25130877 TI - Telechelic poly(2-oxazoline)s with a biocidal and a polymerizable terminal as collagenase inhibiting additive for long-term active antimicrobial dental materials. AB - Dental repair materials face the problem that the dentin below the composite fillings is actively decomposed by secondary caries and extracellular proteases. To address this problem, poly(2-methyloxazoline) with a biocidal and a polymerizable terminal was explored as additive for a commercial dental adhesive. 2.5 wt% of the additive rendered the adhesive contact-active against Streptococcus mutans and washing with water for 101 d did not diminish this effect. The adhesive with 5 wt% additive kills S. mutans cells in the tubuli of bovine dentin. Further, the additive inhibits bacterial collagenase at 0.5 wt% and reduces activity of MMP-9. Human MMPs bound to dentin are inhibited by 96% in a medium with 5 wt% additive. Moreover, no adverse effect on the enamel/dentine shear bond strength was detected. PMID- 25130880 TI - Glutathione S-transferase Mu-1 gene polymorphism in Egyptian patients with idiopathic male infertility. AB - The aim of this study was to examine whether an association exists between glutathione S-transferase Mu-1 (GSTM1) gene polymorphism and idiopathic male infertility. Sixty men with primary idiopathic infertility and 60 fertile men, serving as controls, were recruited for the study. The polymorphism was analysed using polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) technique. The frequency of GSTM1 null genotype was observed to be higher in infertile men 40% in comparison with 33.3% in the fertile men, but this difference was not statistically significant. There was statistically significant difference between cases and controls as regards GSTM1 genotype distribution ((MC) P = 0.006*) in GSTM1-positive men. Patients with the GSTM1 null genotype had significantly lower sperm concentrations and total sperm count when compared with patients with GSTM1-positive genotype. In the control group, men with GSTM1 null genotype had significantly lower sperm concentrations but not total sperm count when compared with men with GSTM1-positive genotype. The results of this study suggest a possible negative effect of GSTM1 null genotype on the spermatogenic potential of the testis. PMID- 25130881 TI - Microbial existence in controlled habitats and their resistance to space conditions. AB - The National Research Council (NRC) has recently recognized the International Space Station (ISS) as uniquely suitable for furthering the study of microbial species in closed habitats. Answering the NRC's call for the study, in particular, of uncommon microbial species in the ISS, and/or of those that have significantly increased or decreased in number, space microbiologists have begun capitalizing on the maturity, speed, and cost-effectiveness of molecular/genomic microbiological technologies to elucidate changes in microbial populations in the ISS and other closed habitats. Since investigators can only collect samples infrequently from the ISS itself due to logistical reasons, Earth analogs, such as spacecraft-assembly clean rooms, are used and extensively characterized for the presence of microbes. Microbiologists identify the predominant, problematic, and extremophilic microbial species in these closed habitats and use the ISS as a testbed to study their resistance to extreme extraterrestrial environmental conditions. Investigators monitor the microbes exposed to the real space conditions in order to track their genomic changes in response to the selective pressures present in outer space (external to the ISS) and the spaceflight (in the interior of the ISS). In this review, we discussed the presence of microbes in space research-related closed habitats and the resistance of some microbial species to the extreme environmental conditions of space. PMID- 25130882 TI - Promoting effects of a single Rhodopseudomonas palustris inoculant on plant growth by Brassica rapa chinensis under low fertilizer input. AB - Several Rhodopseudomonas palustris strains have been isolated from rice paddy fields in Taiwan by combining the Winogradsky column method and molecular marker detection. These isolates were initially screened by employing seed germination and seedling vigor assays to evaluate their potential as inoculants. To fulfill the demand in the present farming system for reducing the application of chemical fertilizers, we assessed the plant growth-promoting effects of the R. palustris YSC3, YSC4, and PS3 inoculants on Brassica rapa chinensis (Chinese cabbage) cultivated under a half quantity of fertilizer. The results obtained showed that supplementation with approximately 4.0*10(6) CFU g(-1) soil of the PS3 inoculant at half the amount of fertilizer consistently produced the same plant growth potential as 100% fertility, and also increased the nitrogen use efficiency of the applied fertilizer nutrients. Furthermore, we noted that the plant growth promotion rate elicited by PS3 was markedly higher with old seeds than with new seeds, suggesting it has the potential to boost the development of seedlings that were germinated from carry-over seeds of poor quality. These beneficial traits suggest that the PS3 isolate may serve as a potential PGPR inoculant for integrated nutrient management in agriculture. PMID- 25130883 TI - Phylogeny and functions of bacterial communities associated with field-grown rice shoots. AB - Metagenomic analysis was applied to bacterial communities associated with the shoots of two field-grown rice cultivars, Nipponbare and Kasalath. In both cultivars, shoot microbiomes were dominated by Alphaproteobacteria (51-52%), Actinobacteria (11-15%), Gammaproteobacteria (9-10%), and Betaproteobacteria (4 10%). Compared with other rice microbiomes (root, rhizosphere, and phyllosphere) in public databases, the shoot microbiomes harbored abundant genes for C1 compound metabolism and 1-aminocyclopropane-1-carboxylate catabolism, but fewer genes for indole-3-acetic acid production and nitrogen fixation. Salicylate hydroxylase was detected in all microbiomes, except the rhizosphere. These genomic features facilitate understanding of plant-microbe interactions and biogeochemical metabolism in rice shoots. PMID- 25130884 TI - Space habitation and microbiology: status and roadmap of space agencies. PMID- 25130886 TI - Linear-dendritic copolymers/indoxacarb supramolecular systems: biodegradable and efficient nano-pesticides. AB - Photodegradable and biocompatible nano-indoxacarb was prepared successfully by encapsulation of indoxacarb with poly(citric acid)-poly(ethylene glycol) poly(citric acid) (PCA-PEG-PCA) ABA type linear-dendritic copolymers both with (nano-IND/TiO2) and without (nano-IND) TiO2 nanoparticles via supramolecular interactions. Preparation of nano-indoxacarb by both formulae was confirmed using spectroscopy and microscopy analyses. TEM images showed small particles with average sizes of 10 nm for nano-IND and 12 nm for nano-IND/TiO2. Interestingly, the rate of degradation of indoxacarb in both nano-IND/TiO2 and nano-IND exposed to UV and natural light was higher than that for free indoxacarb in the presence of TiO2 nanoparticles. Furthermore, results of bioassay experiments on the model pest showed that the essential dosage of pesticide for pest control significantly decreased when nano-IND and nano-IND/TiO2 were used. Because of the higher loading capacity and slower release rate for indoxacarb from nano-IND than from nano-IND/TiO2, and because TiO2 nanoparticles show toxicity in bioassay experiments, nano-IND is introduced as a promising and eco-friendly pesticide system. PMID- 25130885 TI - Microbial monitoring of crewed habitats in space-current status and future perspectives. AB - Previous space research conducted during short-term flight experiments and long term environmental monitoring on board orbiting space stations suggests that the relationship between humans and microbes is altered in the crewed habitat in space. Both human physiology and microbial communities adapt to spaceflight. Microbial monitoring is critical to crew safety in long-duration space habitation and the sustained operation of life support systems on space transit vehicles, space stations, and surface habitats. To address this critical need, space agencies including NASA (National Aeronautics and Space Administration), ESA (European Space Agency), and JAXA (Japan Aerospace Exploration Agency) are working together to develop and implement specific measures to monitor, control, and counteract biological contamination in closed-environment systems. In this review, the current status of microbial monitoring conducted in the International Space Station (ISS) as well as the results of recent microbial spaceflight experiments have been summarized and future perspectives are discussed. PMID- 25130887 TI - Pediatric tracheostomy revisited: a nine-year experience using horizontal intercartilaginous incision. AB - OBJECTIVES/HYPOTHESIS: To describe our tracheostomy procedure using a vertical skin incision and a horizontal intercartilaginous incision and to compare our postoperative results with those in the recent literature. STUDY DESIGN: Retrospective chart review and literature review. METHODS: One hundred eleven children underwent tracheostomy using a vertical skin incision and a horizontal intercartilaginous incision over a 9-year period. A retrospective chart review was undertaken with respect to the following variables: demographics, weight, primary diagnosis, surgical indication, follow-up duration, decannulation, interval between tracheostomy and decannulation, and complications experienced. In addition, the outcomes were compared to results from a literature review. RESULTS: Of the 111 patients, 56 had a history of prolonged intubation, 52 had upper airway obstruction, and three underwent tracheostomy for tracheobronchial toileting. Three (2.7%) patients experienced early major complications without major sequelae, and 14 (12.6%) experienced late major complications. Twenty-one (18.9%) patients were decannulated during the follow-up period, whereas 17 (17.8%) died of their primary disease or tracheostomy-related complications (15 died of their primary disease and two died of tracheostomy-related complications). The complication rates showed overall no differences, but our patient series showed significantly less stomal granulation tissue formation and non-significant trend for less suprastomal collapse as compared with previous literature. CONCLUSIONS: Pediatric tracheostomy using a vertical skin incision and horizontal intercartilaginous incision is comparable with the conventional procedure in terms of complication and mortality rates. Future randomized controlled studies are mandatory to directly compare conventional tracheotomy using a vertical skin incision and a horizontal intercartilaginous incision with our procedure. LEVEL OF EVIDENCE: 4. PMID- 25130888 TI - Evaluation and management of heart rhythm disturbances due to cardiac sarcoidosis. AB - Cardiac sarcoidosis (CS) affects less than 5% of patients with pulmonary or systemic sarcoidosis, but when present is often associated with a spectrum of clinically significant conduction abnormalities and arrhythmias. The cardinal manifestations of CS include conduction disturbances, arrhythmias, or congestive heart failure. Less commonly, there is concealed subclinical disease. The electrophysiologic evaluation for CS includes a history and physical exam, ECG, and echocardiogram for all sarcoidosis patients, along with MRI, PET/nuclear scans, and EPS for certain subsets of patients. Despite variable data to support their efficacy, glucocorticoids should still be considered in the treatment plan of CS. Antiarrhythmics in isolation are often ineffective in controlling ventricular arrhythmias. Cardiac pacemakers have provided important therapy for patients with conduction defects and implantable cardioverter defibrillator (ICD) therapy provides the strongest insurance to prevent fatal arrhythmias from CS. A recent consensus statement provides guidance for clinicians on the diagnosis and management of arrhythmias associated with CS including indications for ICDs. The use of pacemakers, ICD implantation and early implementation of corticosteroid therapy have led to an improvement in the overall prognosis and clinical outcomes of CS. PMID- 25130889 TI - Optimising the detection and management of familial hypercholesterolaemia: central role of primary care and its integration with specialist services. AB - Familial hypercholesterolaemia (FH) is the most common monogenic lipid disorder associated with premature coronary heart disease (CHD). However, the majority of people with FH are undiagnosed or undertreated. Early cholesterol lowering therapy reduces cardiovascular disease mortality in FH. Low awareness and knowledge of FH in specialty and general practice highlights the need for strategies to improve the detection and management of FH. We present an algorithm describing a multidisciplinary approach to FH detection and management. We highlight the role of primary care, and where GPs can work with preventive cardiologists to improve care of FH. Novel strategies to detect index cases with FH are presented including the community laboratory, highlighting patients at high risk of FH, and targeted FH detection through searching the general practice database. General practitioners request over 90% of LDL cholesterol measurements in the community. Once an individual with FH is detected only a small proportion of patients require specialty management with the majority of patients suitably managed in primary care. However, it is crucial to screen family members, as 50% of first-degree family members are expected to have FH due to the autosomal dominant inheritance. PMID- 25130890 TI - Patent foramen ovale influences the presentation of decompression illness in SCUBA divers. AB - BACKGROUND: Few have examined the influence of patent foramen ovale (PFO) on the phenotype of decompression illness (DCI) in affected divers. METHODOLOGY: A retrospective review of our database was performed for 75 SCUBA divers over a 10 year period. RESULTS: Overall 4,945 bubble studies were performed at our institution during the study period. Divers with DCI were more likely to have positive bubble studies than other indications (p<0.001). Major DCI was observed significantly more commonly in divers with PFO than those without (18/1,000 v.s. 3/1,000, p=0.02). Divers affected by DCI were also more likely to require a longer course of hyperbaric oxygen therapy (HBOT) if PFO was present (p=0.038). If the patient experienced one or more major DCI symptoms, the odds ratio of PFO being present on a transoesophageal echocardiogram was 3.2 (p=0.02) compared to those who reported no major DCI symptoms. CONCLUSION: PFO is highly prevalent in selected SCUBA divers with DCI, and is associated with a more severe DCI phenotype and longer duration of HBOT. Patients with unexpected DCI with one or more major DCI symptoms should be offered PFO screening if they choose to continue diving, as it may have considerable prognostic and therapeutic implications. PMID- 25130891 TI - The FM/AM world is shaping the future of deep brain stimulation. PMID- 25130892 TI - Ophthalmic complications of targeted cancer therapy and recently recognized ophthalmic complications of traditional chemotherapy. AB - As our understanding of cancer pathophysiology has increased, so have the number of targeted therapeutic agents available. By targeting specific molecules involved in tumorigenesis, targeted therapeutic agents offer the potential for significant efficacy against tumor cells while minimizing the adverse effects. We highlight the recently recognized ophthalmic complications of targeted cancer therapy, as well as recently recognized complications of traditional chemotherapeutic agents. PMID- 25130893 TI - Pathogenesis of juvenile idiopathic arthritis associated uveitis: the known and unknown. AB - Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and the most prevalent systemic disorder in children with uveitis. The current prevailing opinion is that JIA is a multifactorial, genetically predisposed autoimmune disorder that can be influenced by environmental factors and infections; the specific pathogenesis of JIA-associated uveitis is not understood, however, nor has the relationship between the eye and joint inflammation been established. Nevertheless, subtypes of JIA that are associated with uveitis, oligoarthritis, polyarticular rheumatoid factor negative, and psoriatic arthritis appear to have common pathogenicity. We summarize our current knowledge regarding the pathogenesis of JIA-associated uveitis and discuss the possible role of immune responses and cytokine involvement, genetic associations, and the influence of external triggers in this disease-an association that is supported by data obtained from arthritis research and experimental uveitis models. PMID- 25130894 TI - The promise of telemedicine. AB - We have developed an extraordinary capability to capture and transmit digital ocular imaging, enabling remote interpretation of every aspect of the eye. The issues regarding telemedicine were primarily technical and procedural when this journal first reviewed the topic in 1999. Fourteen years later, telemedicine presents strikingly different challenges-legal, ethical, and professional. Some "tele-ophthalmology" applications have now become a reliable part of daily practice. Although it offers improved health care at lower cost to more people, telemedicine could also radically transform the traditional doctor-patient interaction. PMID- 25130895 TI - The use of vermicompost in organic farming: overview, effects on soil and economics. AB - Vermicomposting is a process in which earthworms are used to convert organic materials into humus-like material known as vermicompost. A number of researchers throughout the world have found that the nutrient profile in vermicompost is generally higher than traditional compost. In fact, vermicompost can enhance soil fertility physically, chemically and biologically. Physically, vermicompost treated soil has better aeration, porosity, bulk density and water retention. Chemical properties such as pH, electrical conductivity and organic matter content are also improved for better crop yield. Nevertheless, enhanced plant growth could not be satisfactorily explained by improvements in the nutrient content of the soil, which means that other plant growth-influencing materials are available in vermicomposts. Although vermicomposts have been shown to improve plant growth significantly, the application of vermicomposts at high concentrations could impede growth due to the high concentrations of soluble salts available in vermicomposts. Therefore, vermicomposts should be applied at moderate concentrations in order to obtain maximum plant yield. This review paper discusses in detail the effects of vermicompost on soil fertility physically, chemically and biologically. Future prospects and economy on the use of organic fertilizers in the agricultural sector are also examined. PMID- 25130896 TI - Stearoyl-CoA desaturase regulates inflammatory gene expression by changing DNA methylation level in 3T3 adipocytes. AB - Adipocytes are one of the primary sources of inflammatory cytokines that drive the low-grade inflammation associated with obesity and obesity-related diseases. Stearoyl-CoA desaturase, a key adipogenic enzyme in rodents and humans, plays significant role in the regulation of adipocyte inflammation via a mechanism that involves the regulation of inflammatory gene expression. In the present study, we tested the hypothesis that the stearoyl-CoA desaturase 1-related regulation of gene expression might be driven by changes in DNA methylation. We showed that stearoyl-CoA desaturase 1 overexpression causes the global hypomethylation of DNA, even as early as 12h after the induction of differentiation, with the greatest difference seen in mature adipocytes. In contrast, both the silencing of stearoyl-CoA desaturase 1 gene expression by siRNA and inhibition of stearoyl-CoA desaturase 1 activity resulted in DNA hypermethylation in 3T3-L1 adipocytes. The analysis of the promoter methylation of 22 genes that are related to the inflammatory response showed that the level of methylation of CpG sites in interleukin-10 receptor a, interleukin-4 receptor a, interleukin-6 signal transducer, and transforming growth factor beta 1 promoters was strongly related to stearoyl-CoA desaturase 1 expression or activity. The changes in methylation at CpG promoter sites correlated with differential expression of the aforementioned genes. The results show that stearoyl-CoA desaturase 1 regulates the level of DNA methylation in adipocytes and suggest that the mechanism by which stearoyl-CoA desaturase 1 affects adipocyte inflammation may involve changes in the methylation of inflammatory genes. PMID- 25130897 TI - Allogeneic hematopoietic stem cell transplantation for T-prolymphocytic leukemia: a report from the French society for stem cell transplantation (SFGM-TC). AB - T-prolymphocytic leukemia (T-PLL), a rare aggressive mature T-cell disorder, remains frequently resistant to conventional chemotherapy. Studies have suggested that allogeneic hematopoietic stem cell transplantation (HSCT) might possibly serve to consolidate the response to initial chemotherapy. The current report summarizes the outcome of 27 T-PLL cases identified in the registry in French Society for stem cell transplantation (SFGM-TC). Prior to HSCT, 14 patients were in complete remission (CR), 10 in partial response, three refractory, or in progression. Following HSCT, 21 patients achieved CR as best response. With a median follow-up for surviving patients of 33 (range, 6-103) months, 10 patients are still alive in continuous CR. Overall survival and progression-free survival estimates at 3 yr were 36% (95% CI: 17-54%) and 26% (95% CI: 14-45%), respectively. The relapse incidence after HSCT was 47% occurring at a median of 11.7 (range, 2-24) months. Overall cumulative incidence of transplant-related mortality was 31% at 3 yr. These results suggest that HSCT may allow long-term survival in patients with T-PLL following induction treatment; however, it is associated with a significant rate of toxicity. PMID- 25130898 TI - Self-awakening improves alertness in the morning and during the day after partial sleep deprivation. AB - The ability to awaken at a predetermined time without an alarm is known as self awakening. Self-awakening improves morning alertness by eliminating sleep inertia; however, the effects of self-awakening on daytime alertness and alertness that has deteriorated as a result of sleep loss are unknown. The aim of this study was to determine the effects of self-awakening on both morning and daytime alertness after partial sleep deprivation. Fifteen healthy males without the habit of self-awakening participated in a cross-over trial including forced awakening and self-awakening conditions. In each condition, participants' sleep was restricted to 5 h per night in their homes for 4 consecutive days. They completed a psychomotor vigilance task and subjective ratings of sleepiness immediately upon awakening each morning. On the fourth day, participants completed subjective ratings of sleepiness, a psychomotor vigilance task and sleep latency tests in the laboratory seven times at 1-h intervals during the day. The response speed on the psychomotor vigilance task, in the morning and during the day, was higher in the self-awakening than the forced awakening condition. Our results showed that self-awakening improved alertness (assessed by response speeds) by reducing sleep inertia and alleviated daytime sleepiness heightened by partial sleep deprivation. PMID- 25130900 TI - Correction of penile torsion and chordee by mobilization of urethra with spongiosum in chordee without hypospadias. AB - OBJECTIVE: To investigate the feasibility of correcting coexistent penile torsion and chordee without hypospadias by mobilization of the urethra and spongiosum. MATERIALS AND METHODS: A retrospective study of nine patients with simultaneous penile torsion and chordee without hypospadias was undertaken between January 2006 and December 2012. During this period, a total of 364 cases of hypospadias and 38 of chordee without hypospadias were operated on, making a total of 402 patients with hypospadias-related complexes. The same steps were used for correction of both torque and chordee. After a circumcoronal incision, the penis was fully degloved and the spongiosum with urethra was lifted up off the cavernosa. Next, mobilization of the hypoplastic urethra with spongiosum was extended into the glans. If chordee or torque persisted, urethral mobilization was performed proximally up to the bulbar urethra, as required. Spongioplasty and glansplasty were done and a per-urethral stent was kept in for three to five days. RESULTS: The age of the patients ranged from 5 to 16 years (median 6 years). Penile torsion ranged from 30 degrees to 120 degrees , with a median of 75 degrees . Ventral chordee ranged from 45 degrees to 100 degrees , with a median of 50 degrees . A ratio of 1:9.6 was found for chordee without hypospadias compared to the total hypospadias cases, with an incidence of 9.5%. The ratio of chordee without hypospadias with torsion compared to the total hypospadias cases was 1:29. There was an incidence of chordee without hypospadias with penile torsion of 3.5% in all patients with hypospadias. The ratio of chordee without hypospadias with torsion to only chordee without hypospadias was 1:1.71, with an incidence of 37.0%. Every step contributed to the correction of curvature and torsion. Chordee was corrected in two patients by penile degloving and lifting of the spongiosa off the urethral plate; three patients required additional mobilization of the urethra into the glans. Another two patients needed proximal urethral mobilization and one required a dorsal plication. In five patients, torque was corrected by penile degloving, lifting of the spongiosa and mobilization of the urethra into the glans; four patients required further proximal urethral mobilization. All patients had excellent functional and cosmetic results. No residual chordee or torque was observed in any patient on follow-up at 12-24 months. CONCLUSION: The technique of distally mobilizing a hypoplastic urethra with spongiosum from the corpora into the glans, and proximally up to the bulbar region corrects moderate to severe chordee and torsion with excellent cosmetic results. The incidence of torsion with chordee without hypospadias was 3.5% of all cases of hypospadias. PMID- 25130901 TI - The challenges in diagnosis and gender assignment in disorders of sex development presenting to a pediatric surgical unit in a developing country: the role of laparoscopy and simple tests for gender identity. AB - OBJECTIVE: We aimed to assess how the diagnosis and determination of gender identity of disorders of sex development (DSD) is different in a developing country from Western medicine, and whether a pediatric surgery department can determine the underlying diagnosis and use simple tools to determine the likely gender identity (GI). MATERIAL AND METHODS: We reviewed the records of DSD patients admitted to the Department of Pediatric Surgery, Chittagong Medical College & Hospital (CMCH), Chittagong, Bangladesh, from January 2006 to December 2012 and performed a cross-sectional study on GI and gender-related behavior in these patients during the year 2012. DSD boys and girls answered a GI interview and had their gender role behavior assessed by observations of structural toy play and analyzed for differences in scores. RESULTS: This cohort of DSD patients presented in mid-childhood (6 months-16 years, mean 6.9 years) rather than infancy, and 30% came from consanguineous unions. Congenital adrenal hyperplasia (CAH) constituted only 11 of 50 (22%) of the DSD cohort, and not all families had access to steroid hormone replacement. A simple assessment of GI and gender related behavior allowed effective gender assignment, as there was significant difference between DSD boys and girls in GI and gender-related behavior score. CONCLUSIONS: DSD management in Bangladesh provides some unique challenges because of limited resources. A national reference laboratory for biochemical and genetic testing and development of a quaternary referral center for DSD patients will be helpful. Continued use of the GI interview and gender-related behavior study will enable effective interim decisions about diagnosis and management. PMID- 25130899 TI - Cellular zinc levels are modulated by TRPML1-TMEM163 interaction. AB - Mucolipidosis type IV (MLIV) is caused by loss of function mutations in the TRPML1 ion channel. We previously reported that tissue zinc levels in MLIV were abnormally elevated; however, the mechanism behind this pathologic accumulation remains unknown. Here, we identify transmembrane (TMEM)-163 protein, a putative zinc transporter, as a novel interacting partner for TRPML1. Evidence from yeast two-hybrid, tissue expression pattern, co-immunoprecipitation, mass spectrometry and confocal microscopy studies confirmed the physical association of TMEM163 with TRPML1. This interaction is disrupted when a part of TMEM163's N-terminus was deleted. Further studies to define the relevance of their interaction revealed that the plasma membrane (PM) levels of TMEM163 significantly decrease when TRPML1 is co-expressed in HEK-293 cells, while it mostly localizes within the PM when co-expressed with a mutant TRPML1 that distributes mostly in the PM. Meanwhile, co-expression of TMEM163 does not alter TRPML1 channel activity, but its expression levels in MLIV patient fibroblasts are reduced, which correlate with marked accumulation of zinc in lysosomes when these cells are acutely exposed to exogenous zinc (100 MUM). When TMEM163 is knocked down or when TMEM163 and TRPML1 are co-knocked down in HEK-293 cells treated overnight with 100 nm zinc, the cells have significantly higher intracellular zinc levels than untreated control. Overall, these findings suggest that TMEM163 and TRPML1 proteins play a critical role in cellular zinc homeostasis, and thus possibly explain a novel mechanism for the pathological overload of zinc in MLIV disease. PMID- 25130902 TI - Chironomidae and Oligochaeta for water quality evaluation in an urban river in southeastern Brazil. AB - Considering the importance of benthic macroinvertebrates for diagnosis of variations in the ecological conditions of aquatic habitats, the aim of this study was to investigate the structure of the Chironomidae and Oligochaeta assemblages along an organic pollution gradient. The fauna specimens were obtained with the use of artificial substrates, and the environmental variables were recorded at five sites of the Sao Lourenco River, during 12 months. Metrics of the assemblage and detrended correspondence analysis were used to verify the response of the fauna to the pollution gradient. Procrustes analysis was used to verify whether the data on the Chironomidae and Oligochaeta assemblages, as well as the taxonomic and numerical resolution of these groups, provide similar results in relation to the pollution gradient. The richness, evenness, and taxonomic composition of the Chironomidae and Oligochaeta assemblages varied significantly among the collection sites, with distinct conservation conditions. Genera of the subfamilies Orthocladiinae and Tanypodinae were associated with the sites upstream of the urban area, where the dissolved oxygen levels are higher. Species of Oligochaeta and the genus Chironomus were associated with more organically polluted sites. No concordance was observed in the response of the Chironomidae and Oligochaeta assemblages in relation to the environmental variables, indicating the need to use both groups in biomonitoring studies. On the other hand, both the data on composition (presence or absence) and those on the lowest taxonomic resolution (abundance of subfamilies) were effective to diagnose the pollution gradient in the river studied. Therefore, when the environmental conditions along a river's gradient are contrasting, we suggest the use of the lowest taxonomic resolution of Chironomidae and Oligochaeta in biomonitoring. That procedure considerably reduces the assessment time, besides being a method that can be used by people not specializing in the taxonomy of groups. PMID- 25130903 TI - Labeo rosae (Cypriniformes: Cyprinidae) in the Congo basin: a relict distribution or a historical introduction? AB - Labeo rosae, a species with a native range in Southern Africa, was discovered in the Congo basin by re-identification of two museum specimens previously identified as Labeo mesops. The occurrence of this species in the upper Congo implies a range extension of the species of more than 1000 km. Although the species' distribution is mirrored by that of some other Cypriniformes, its occurrence in the Congo might be due to introduction by humans. PMID- 25130904 TI - Atopy does not affect the frequency of adenotonsillar hypertrophy and sleep apnoea in children who snore. AB - AIM: Viral respiratory infections and atopy have been implicated in the pathogenesis of adenotonsillar hypertrophy and obstructive sleep apnoea (OSA), but the role of atopy is controversial. We aimed to test our hypothesis that atopy, expressed as physician-diagnosed eczema, was associated with adenotonsillar hypertrophy and OSA among children who snored. METHODS: Data on children who snored and were referred for polysomnography were reviewed. The primary outcome measures were adenotonsillar hypertrophy and OSA. RESULTS: We analysed data on 855 children with a mean age (+/-standard deviation) of 6.3 (+/ 2.5) years and median obstructive apnoea-hypopnea index of 2.1 episodes per hour. Of the 855 subjects, 133 (15.6%) had physician-diagnosed eczema, 591 (69.1%) had adenoidal hypertrophy, 605 (70.8%) had tonsillar hypertrophy, 219 (25.6%) were obese and 470 (55%) had OSA. Eczema was not related to adenoidal or tonsillar hypertrophy after adjustment for gender and age, with odds ratios (OR) of 1.00 (95% confidence interval 0.67-1.49; p = 0.98) and 0.88 (95% confidence interval 0.59-1.32; p = 0.54), respectively. Similarly, eczema did not affect OSA frequency after adjustment for adenoidal and tonsillar hypertrophy, obesity, gender and age, with an adjusted OR of 0.82 (0.56-1.21; p = 0.32). CONCLUSIONS: Atopy was not related to adenotonsillar hypertrophy or OSA in children who snore. PMID- 25130905 TI - Arterial supply to the thyroid gland and the relationship between the recurrent laryngeal nerve and the inferior thyroid artery in human fetal cadavers. AB - The aim of this study was to identify the arterial supply to the thyroid gland and the relationship between the inferior thyroid artery (ITA) and the recurrent laryngeal nerve (RLN) in fetal cadavers using anatomical dissection. The anterior necks of 200 fetuses were dissected. The origins of the superior thyroid artery (STA) and the ITA and location of the ITA in relation to the entrance of the thyroid lobe were examined. The relationship between the ITA and the RLN was determined. The origins of the STA were classified as: external carotid artery, common carotid artery (CCA), and the thyrolingual trunk. The origins of the ITA were the thyrocervical trunk and the CCA. The ITA was absent on the left side in two cases. The relationship of the RLN to the ITA fell into seven different types. Type 1: the RLN lay posterior to the artery; right (42.5%), left (65%). Type 2: the RLN lay anterior to the artery; right (40.5%), left (22.5%). Type 3: the RLN lay parallel to the artery; right (11.5%), left (7%). Type 4: the RLN lay between the two branches of the artery; right (1%), left (3.5%). Type 5: The extralaryngeal branch of the RLN was detected before it crossed the ITA; right (4.5%), left (0%). Type 6: the ITA lay between the two branches of the RLN; right (0%), left (0.5%). Type 7: the branches of the RLN lay among the branches of the ITA; right (0%), left (0.5%). The results from this study would be useful in future thyroid surgeries. PMID- 25130906 TI - Protein localization of epidermal growth factor in sheep ovaries and improvement of follicle survival and antrum formation in vitro. AB - The aims of this study were to characterize EGF protein expression in ovine ovaries and to verify the effect of EGF on the in vitro development of isolated pre-antral follicles. After collection, ovarian tissue was fixed for immunohistochemical analysis. Additional pairs of ovaries were collected, and secondary follicles were cultured for 18 days in alpha-MEM(+) (control) alone or supplemented with EGF (1, 10 or 50 ng/ml). The immunostaining for EGF was observed in oocytes from pre-antral and antral follicles, in granulosa cells of primary and secondary follicles, as well as in cumulus and mural cells of antral follicles. After 18 days, the results showed that treatment with 50 ng/ml EGF significantly increased the percentage of morphologically normal follicles compared with the control group (alpha-MEM(+) ) and significantly reduced the precocious extrusion of oocytes and increased the percentage of antral follicles compared with the control and 1 ng/ml EGF. All the treatments induced a progressive and significant increase of the follicular diameter throughout the period of culture. However, there were no significant differences in follicular diameter or in the daily growth rate among treatments. In conclusion, this study demonstrated the presence of EGF in ovine ovaries. Moreover, 50 ng/ml EGF increased the percentage of normal follicles and improved antrum formation in isolated ovine follicles after 18 days of in vitro culture. PMID- 25130907 TI - DNA barcoding of wild edible mushrooms consumed by the ethnic tribes of India. AB - Wild edible mushrooms are consumed by the tribes of Meghalaya in the North Eastern region of India, as part of their ethnic cuisine because of their favored organoleptic characteristics and traditionally known health benefits. Majority of these mushrooms have not yet been characterized in detail and are slowly shrinking in their natural habitats owing to anthropogenic factors and climate change. In the present study, representative specimens of ten morphologically distinct groups of wild edible mushrooms available in the traditional markets and their respective forest habitats, were subjected to multi-loci molecular characterization using SSU, ITS, RPB1 and RPB2 markers. The species identities inferred for the ten mushroom types using the SSU marker matched their morphological description in the case of four morphological groups only whereas the ITS marker successfully resolved the species identity for nine out of the ten mushroom groups under study. Both the protein coding gene markers RPB1 and RPB2 successfully resolved the species identity for three out of the ten morphologically distinct groups. Finally the most likely identity of the wild edible mushrooms under study has been suggested by matching their unique morphological characteristics with the generated DNA barcoding data. The present molecular characterization reveals the ten widely consumed wild mushroom types of Meghalaya, India to be Gomphus floccosus, Lactarius deliciosus, Lactarius volemus, Cantharellus cibarius, Tricholoma viridiolivaceum, Inocybe aff. sphaerospora, Laccaria vinaceoavellanea, Albatrellus ellisii, Ramaria maculatipes and Clavulina cristata. The final species identity generated by the ITS marker matched more accurately with the morphological characteristics/appearance of the specimens indicating the ITS region as a reliable barcode for identifying wild edible mushrooms. PMID- 25130908 TI - Cloning, expression and cellular localization of the Doublesex gene in the water flea, Daphnia carinata, during different developmental stages. AB - In this study, one of Doublesex genes from the common freshwater cladoceran Daphnia carinata, designated DapcaDsx1, was cloned using primers based on homologous sequences and rapid amplification of cDNA ends (RACE). qPCR was employed to quantify differences in DapcaDsx1 expression between the different sexual phases, with expression levels being higher in sexual females. The role of DapcaDsx1 in the reproductive transformation was further investigated in parthenogenetic-phase females and sexual-phase females using whole-mount in situ hybridization. This cellular localization study showed specific expression of DapcaDsx1 in the thoracic segments, second antenna and part of the ventral carapace. Higher expression levels were exhibited in sexual females compared to parthenogenetic females. This suggests that the DapcaDsx1 gene plays significant roles in switching modes of reproduction and during sexual differentiation. PMID- 25130909 TI - Diverse expression pattern of wheat transcription factors against abiotic stresses in wheat species. AB - Abiotic stress including drought and salinity affects quality and yield of wheat varieties used for the production of both bread and pasta flour. bZIP, MBF1, WRKY, MYB and NAC transcription factor (TF) genes are the largest transcriptional regulators which are involved in growth, development, physiological processes, and biotic/abiotic stress responses in plants. Identification of expression profiling of these TFs plays a crucial role to understand the response of different wheat species against severe environmental changes. In the current study, expression analysis of TaWLIP19 (wheat version of bZIP), TaMBF1, TaWRKY10, TaMYB33 and TaNAC69 genes was examined under drought and salinity stress conditions in Triticum aestivum cv. (Yuregir-89), Triticum turgidum cv. (Kiziltan 91), and Triticum monococcum (Siyez). After drought stress application, all five selected genes in Kiziltan-91 were induced. However, TaMBF1 and TaWLIP19 were the only downregulated genes in Yuregir-89 and Siyez, respectively. Except TaMYB33 in Siyez, expression level of the remaining genes increased under salt stress condition in all Triticum species. For determination of drought response to selected TF members, publicly available RNA-seq data were also analyzed in this study. TaMBF1, TaWLIP19 and TaNAC69 transcripts were detected through in silico analysis. This comprehensive gene expression analysis provides valuable information for understanding the roles of these TFs under abiotic stresses in modern wheat cultivars and ancient einkorn wheat. In addition, selected TFs might be used for determination of drought or salinity-tolerant and susceptible cultivars for molecular breeding studies. PMID- 25130910 TI - Thermodynamic stability and kinetic inertness of a Gd-DTPA bisamide complex grafted onto gold nanoparticles. AB - Gold nanoparticles coated by gadolinium (III) chelates (Au@DTDTPA) where DTDTPA is a dithiolated bisamide derivative of diethylenetriamine-N,N,N',N'',N'' pentaacetic acid (DTPA), constituted contrast agents for both X-ray computed tomography and magnetic resonance imaging. In an MRI context, highly stable Gd(3+) complexes are needed for in vivo applications. Thus, knowledge of the thermodynamic stability and kinetic inertness of these chelates, when grafted onto gold nanoparticles, is crucial since bisamide DTPA chelates are usually less suited for Gd(3+) coordination than DTPA. Therefore, these parameters were evaluated by means of potentiometric titrations and relaxivity measurements. The results showed that, when the chelates were grafted onto the nanoparticle, not only their thermodynamic stability but also their kinetic inertness were improved. These positive effects were correlated to the chelate packing at the nanoparticle surface that stabilized the corresponding Gd(3+) complexes and greatly enhanced their kinetic inertness. PMID- 25130911 TI - Ancient DNA evidence reveals that the Y chromosome haplogroup Q1a1 admixed into the Han Chinese 3,000 years ago. AB - OBJECTIVES: Y chromosome haplogroup Q1a1 is found almost only in Han Chinese populations. However, it has not been found in ancient Han Chinese samples until now. Thus, the origin of haplogroup Q1a1 in Han Chinese is still obscure. This study attempts to provide answer to this question, and to uncover the origin and paternal genetic structure of the ancestors of the Han Chinese. METHODS: Eighty nine ancient human remains that were excavated from the presumed geographic source of the Han Chinese and dated to approximately 3,000 years ago were treated by the amelogenin gene polymerase chain reaction test, to determine their sex. Then, Y chromosome single nucleotide polymorphisms were subsequently analyzed from the samples detected as male. RESULTS: Samples from 27 individuals were successfully amplified. Their haplotypes could be attributed to haplogroups N, O*, O2a, O3a, and Q1a1. Analyses showed that the assigned haplogroup of each sample is correlated to the suspected social status and observed burial custom associated with the sample. CONCLUSIONS: The origins of the observed haplotypes and their distribution in present day Han Chinese and in the samples suggest that haplogroup Q1a1 was probably introduced into the Han Chinese population approximately 3,000 years ago. PMID- 25130913 TI - Local analyses of ionic liquid/solid interfaces by frequency modulation atomic force microscopy and photoemission spectroscopy. AB - Local analyses of ionic liquid/solid electrode interfaces at a controlled electrode potential are of fundamental importance to understanding the origin and properties of the electric double layer at the interfaces, which is necessary for their application to electrochemical devices. This account summarizes our recent achievements of such analyses by using the novel analytical tools of electrochemical frequency modulation AFM (EC-FM-AFM) and electrochemical photoemission spectroscopy (EC-PES). Rather stable stepped structures composed of layers of ion pairs and softer solvation layers outside of the imaged layer were clearly visualized by FM-AFM depending on the substrates. An extremely extended diffusion layer was directly observed by EC-PES during the electrodeposition of metal ion solutes. PMID- 25130912 TI - Platelet activation biomarkers in Berkeley sickle cell mice and the response to prasugrel. AB - Vaso-occlusive crisis (VOC) is a common complication that occurs in sickle cell disease (SCD) patients. Although underlying mechanisms of VOC remain unclear, platelet activation has been associated with VOC. In the present study, plasma adenine nucleotide measurements using LC-ESI-MS/MS showed that plasma ADP in the Berkeley murine model of SCD was significantly higher (applox. 2.7-fold increase) compared with control mice. Assessment of platelet activation markers using flow cytometry indicated that in SCD mice at steady state (8 weeks old), circulating platelets were partially activated and this tended to increase with age (15 weeks old). The administration of prasugrel, a thienopiridyl P2Y12 antagonist, did not affect the activation state of circulating platelets suggesting P2Y12 independent mechanism of activation. In this murine SCD model, ex vivo addition of ADP or PAR4 TRAP resulted in further platelet activation as assessed by expression of activated GPIIb/IIIa and P-selectin both at 8 and 15 weeks. In 15 weeks old SCD mice, agonist-induced increases in activation markers were enhanced compared to control mice. Oral administration of prasugrel effectively inhibited ex vivo platelet activation consistent with clinical data in patients with SCD. In conclusion, in the Berkeley murine model of SCD, we found evidence of basal and agonist-stimulated platelet activation which could in part be attenuated by prasugrel. These data are consistent with observations made in patients with SCD and suggest possible utility of this murine model and prasugrel therapy in exploring treatment options for patients with SCD. PMID- 25130914 TI - Inability to Measure M-Protein With Capillary Zone Electrophoresis (CAPPILLARYS 2) in Tracings With NonDiscernable Peaks. AB - BACKGROUND: We performed a retrospective study to illustrate the challenges with quantifying monoclonal (M)-protein in the cases of serum protein capillary zone electrophoresis (SPCZE) where no discernable peak is apparent. MATERIALS AND METHODS: We retrospectively reviewed 160 serum immunofixation electrophoresis (SIFE) that were performed at Memorial Hermann Hospital-Texas Medical Center between October 2013 and November 2013 and we identified the positive SIFE results. The corresponding SPCZE of the positive SIFE were retrieved and evaluated for the ability to quantify M-proteins in them. We define the ability to quantify M-protein as the ability for the operator of the SPCZE to identify a discernable peak and to be able to manually gate the area under the peak. RESULTS: Twenty-two cases of SIFE detected a monoclonal immunoglobulin. Of the corresponding 22 SPCZE, we could not quantify the M-protein in 6 (27.3%) of the cases. CONCLUSION: We have shown several cases where we were not able to quantify the M-protein with SPCZE. This poses a challenge in the diagnosis and management of these patients. PMID- 25130915 TI - Human papillomavirus genotype distribution in invasive cervical cancer in Bosnia and Herzegovina. AB - PURPOSE: Countries of the former Yugoslavia bear some of the highest cervical cancer burden in Europe. In Bosnia and Herzegovina (B&H), data on human papillomavirus (HPV) genotype distribution among cervical cancer cases is scarce. This baseline information is critical in order to evaluate the impact of prophylactic HPV vaccines. This study aims to provide specific information for B&H. METHODS: The final analysis comprised 283 cases of invasive cervical cancer identified at the Polyclinic for Laboratory Diagnostic, University Clinical Center Tuzla in B&H between 1984 and 2004. HPV was detected through amplification of HPV DNA using SPF-10 broad spectrum primers followed by deoxyribonucleic acid enzyme inmunoassay and genotyping by reverse line probe assay (LiPA(25), version 1). RESULTS: Most cases (92.2%) were histologically classified as squamous cell carcinoma (SCC). A total of 268 cases (94.7%) were positive for HPV. Infections were mainly present as single (95.5%) and HPV16 and 18 accounted for 77.8% of the positive cases. The next most common HPV types were HPV45 (4.4%), HPV33 (3.1%), HPV51 (2.3%) and HPV31 (2.2%). The mean age of cases infected with the seven most common types worldwide (HPV16/18/45/31/33/52/58) was 51.1 (SD=11.6), six years younger than the one for cases infected with other types (56.3, SD=12.9). CONCLUSIONS: Available HPV vaccines could potentially prevent 77.8% of Bosnian cervical cancer cases (i.e. those associated with HPV16/18). If the reported magnitude of the cross-protection of licensed vaccines for non-vaccine HPV types is long lasting, an additional 6 to 10% of cases could be prevented. PMID- 25130917 TI - Vacuum-free, maskless patterning of Ni electrodes by laser reductive sintering of NiO nanoparticle ink and its application to transparent conductors. AB - We introduce a method for direct patterning of Ni electrodes through selective laser direct writing (LDW) of NiO nanoparticle (NP) ink. High-resolution Ni patterns are generated from NiO NP thin films by a vacuum-free, lithography-free, and solution-processable route. In particular, a continuous wave laser is used for the LDW reductive sintering of the metal oxide under ambient conditions with the aid of reducing agents in the ink solvent. Thin (~ 40 nm) Ni electrodes of glossy metallic surfaces with smooth morphology and excellent edge definition can be fabricated. By applying this method, we demonstrate a high transmittance (>87%), electrically conducting panel for a touch screen panel application. The resistivity of the Ni electrode is less than an order of magnitude higher compared to that of the bulk Ni. Mechanical bending test, tape-pull test, and ultrasonic bath test confirm the robust adhesion of the electrodes on glass and polymer substrates. PMID- 25130916 TI - Using self-reported health measures to predict high-need cases among Medicaid eligible adults. AB - OBJECTIVE: To assess the ability of different self-reported health (SRH) measures to prospectively identify individuals with high future health care needs among adults eligible for Medicaid. DATA SOURCES: The 1997-2008 rounds of the National Health Interview Survey linked to the 1998-2009 rounds of the Medical Expenditure Panel Survey (n = 6,725). STUDY DESIGN: Multivariate logistic regression models are fitted for the following outcomes: having an inpatient visit; membership in the top decile of emergency room utilization; and membership in the top cost decile. We examine the incremental predictive ability of six different SRH domains (health conditions, mental health, access to care, health behaviors, health-related quality of life [HRQOL], and prior utilization) over a baseline model with sociodemographic characteristics. Models are evaluated using the c statistic, integrated discrimination improvement, sensitivity, specificity, and predictive values. PRINCIPAL FINDINGS: Self-reports of prior utilization provide the greatest predictive improvement, followed by information on health conditions and HRQOL. Models including these three domains meet the standard threshold of acceptability (c-statistics range from 0.703 to 0.751). CONCLUSIONS: SRH measures provide a promising way to prospectively profile Medicaid-eligible adults by likely health care needs. PMID- 25130918 TI - Increase in skin surface elasticity in normal volunteer subjects following the use of copper oxide impregnated socks. AB - BACKGROUND: Copper is an essential mineral involved in the formation and stabilisation of extracellular skin proteins. As copper can be absorbed through intact skin, we reasoned that using socks containing copper-impregnated fibres may have an effect on skin elasticity. METHODS: A double blind, placebo controlled study was conducted in which one group of healthy volunteers (n = 32) wore socks with fibres containing microscopic copper oxide particles and the other group wore identical socks without copper oxide (n = 28). The socks were worn for at least 10 h a day for 4 weeks. Skin elasticity measurements were taken from three separate test sites on the side of the ankle using a Cutometer at baseline and after 2 and 4 weeks of product use. RESULTS: There was an increase in the mean net skin elasticity (R5) of 6.4% (P = 0.6) and 31.4% (P = 0.004) after 2 and 4 weeks respectively, in the group of individuals that used the copper oxide containing socks, but no increase in the group of individuals that used the control socks. Similarly, there was an increase in the mean biological elasticity (R7 values) of 3% (P = 0.55) and 20.7% (0.014) after 2 and 4 weeks, respectively, only in the group of individuals that used the copper oxide containing socks. The differences between treatments (i.e. socks used) were statistically significant at 4 weeks (P = 0.0058 and P = 0.0327 for R5 and R7, respectively). CONCLUSION: Using copper oxide containing socks results in an increase in skin elasticity of the feet. PMID- 25130919 TI - Effects of diabetes mellitus on left atrial volume and functions in normotensive patients without symptomatic cardiovascular disease. AB - PURPOSE: Left atrial (LA) size has been shown to be a predictor of adverse cardiovascular outcomes. The aim of the study was to evaluate the direct effect of diabetes mellitus (DM) on left atrial volume and phasic functions by using real-time three-dimensional echocardiography (RT3DE) in a population of patients free of symptomatic cardiovascular disease and hypertension. METHODS: Comprehensive transthoracic echocardiographic examination was performed on 40 consecutive patients with DM (20 male, age: 50.5+/-7.3 years) and 40 healthy controls (20 male, age: 48.4+/-6.7 years). In addition to conventional 2D echocardiographic measurements RT3DE was performed to assess LA volumes and phasic functions. RESULTS: There were no significant difference between groups regarding parameters reflecting LV systolic function as LV diameters and ejection fraction. However, regarding parameters reflecting LV diastolic function; transmitral deceleration time and E/E' ratio values were significantly higher and majority of early diastolic tissue Doppler velocity values were significantly lower in diabetic patients compared with controls. RT3DE demonstrated significantly higher LA maximum and minimum volumes for diabetic patients compared with controls (40.9+/-11.9 vs 34.6+/-9.3 mL, p: 0.009 and 15.6+/-5.9 vs 11.9+/-4.6 mL, p: 0.002, consecutively). LA total emptying fraction (TEF), expansion index (EI) and active emptying fraction (AEF) were found to be significantly lower in diabetics reflecting depressed LA reservoir and pump functions. There was no significant difference between groups regarding passive emptying fraction (PEF) which is assumed to be a marker of left atrial conduit function. CONCLUSION: Patients with type 2 diabetes mellitus were found to have increased LA volume and impaired atrial compliance and contractility. Evaluation of asymptomatic diabetic patients by using RT3DE atrial volume analysis may facilitate recognition of subtle myocardial alterations related with type 2 diabetes. PMID- 25130924 TI - The cultural dimension of tightness-looseness: An analysis of situational constraint in Estonia and Greece. AB - The importance of tightness-looseness as a dimension that explains a considerable amount of variance between cultures was demonstrated by Gelfand et al. (2011). Tight nations have many strong norms and a low tolerance of deviant behaviour, whereas loose nations have weak social norms and a high tolerance of deviant behaviour. The main aim of the current studies was to examine situational constraint in Estonia and Greece: that is, how the cultural dimension of tightness-looseness is manifested in everyday situations in those two countries. The findings of a questionnaire study (Study 1) suggested that, in general, there is higher constraint across everyday situations in Greece than in Estonia, but situational constraint in Greece is especially strong in school and organisational settings where people have hierarchically structured roles. The results of an observational study (Study 2) revealed a relatively high agreement between appropriateness of certain behaviours as judged by the respondents in Study 1 and the frequencies of observed behaviours in the two countries. Our findings suggest that the strength of situations may substantially vary both within and across cultures, and that the attitudes of the members about situational strength in their respective cultures are in concordance with observations of situations by neutral observers in how people in general behave in their culture. PMID- 25130920 TI - Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta analysis. AB - AIMS: The efficacy of the once-daily prandial GLP-1 receptor agonist lixisenatide plus basal insulin in T2DM was assessed by pooling results of phase III trials. METHODS: A meta-analysis was performed of results from three trials in the GetGoal clinical program concerning lixisenatide or placebo plus basal insulin with/without OADs. The primary endpoint was change in HbA1c from baseline to week 24. Secondary endpoints were change in PPG, FPG, insulin dose, and weight from baseline to week 24. Hypoglycemia rates and several composite endpoints were assessed. RESULTS: Lixisenatide plus basal insulin was significantly more effective than basal insulin alone at reducing HbA1c at 24 weeks. Composite and secondary endpoints were improved significantly with lixisenatide plus basal insulin, with the exception of FPG, which showed no significant difference between the groups. Lixisenatide plus basal insulin was associated with an increased incidence of hypoglycemia versus basal insulin alone. CONCLUSIONS: Lixisenatide plus basal insulin resulted in significant improvement in glycemic control versus basal insulin alone, particularly in terms of controlling PPG. Prandial lixisenatide in combination with basal insulin is a suitable option for treatment intensification in patients with T2DM insufficiently controlled with basal insulin, as these agents have complementary effects on PPG and FPG, respectively. PMID- 25130925 TI - Cystic lesions in the kidney of flower horn fish, hybrid cichlid. PMID- 25130926 TI - First report of a rare mutation in a Polish patient with painful late-onset transthyretin amyloidosis. PMID- 25130927 TI - Individual factors enhance poor health-related quality of life outcome in multiple sclerosis patients. Significance of predictive determinants. AB - BACKGROUND: Individual factors in multiple sclerosis (MS) patients may modify the reliability of health-related quality of life (HRQOL) assessment. Knowledge of these effects may enable physicians to identify patients at risk for poor perceived health. OBJECTIVE: To investigate what individual factors may interact with MS symptoms and their severity to modify the reliability of HRQOL assessment; to explore the predictive values of the significant variables identified. METHODS: HRQOL was assessed in 57 patients by the 36-Item Short Form Health Survey (SF-36). The Physical Component Summary and Mental Component Summary were dichotomized and applied as dependent variables for logistic regression analysis. The Functional Independence Measure (FIM), Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), Cognitive Behavioral Assessment (CBA) and specific individual factors were tested as independent variables. Two-way contingency tables were used to calculate the predictive values. RESULTS: Unemployment, smoking, and night waking were the most significant individual factors. Introversion, physical pain and difficulty falling asleep were also significant. EDSS-total >=2, EDSS-pyramidal >=2, FIM <=123, FSS >=5, depressive manifestations and bowel/bladder dysfunction were significant MS-related determinants. Sensitivity and specificity differed widely for each variable. CONCLUSIONS: Individual factors have relevance in HRQOL assessment. Their identification may help physicians construct the patient's risk profile. Sensitivity and specificity add weight to the significance of variables. PMID- 25130928 TI - Anatomical localization of p53 mutated tumors: A radiographic study of human glioblastomas. AB - Accumulating evidence has suggested that tumor location is linked to the genetic profile of gliomas. Therefore, the aim of this study was to investigate the anatomical characteristics of p53-mutated glioblastomas. We also sought to provide new insight into the possible niche locations of cells of glioblastoma origin. In order to accomplish this, preoperative magnetic resonance images from 163 patients with primary glioblastomas were retrospectively analyzed. All tumors were manually marked and registered to the standard space. Using the voxel-based lesion-symptom mapping approach, voxels exhibiting the strongest correlations with p53 mutants were identified. T-values of voxels that were greater than 95% of the permutations were factored into the results of the mapping analysis. Distinct anatomical characteristics between p53-mutated and wild-type glioblastomas were demonstrated using this approach. More specifically, we found that p53-mutated glioblastomas were preferentially located in the frontal lobe in the area surrounding the rostral extension of the lateral ventricles. The distinct anatomical characteristics of p53-mutated and wild-type glioblastomas provide further evidence that these gliomas arise from distinct niche locations. PMID- 25130929 TI - Increased proinflammatory cytokines in sera of patients with multifocal motor neuropathy. AB - BACKGROUND: Multifocal motor neuropathy (MMN) is characterized by clinical improvement with intravenous immunoglobulin and the frequent detection of anti ganglioside antibodies. However, the immunological background of the neuronal damage in MMN is still unclear. OBJECTIVE: The aim of this study is to investigate abnormalities in the cytokine and chemokine profiles of MMN patients. METHODS: Sera from 16 patients with MMN, 16 patients with sporadic amyotrophic lateral sclerosis (ALS), and 15 patients with other non-inflammatory neurological diseases (ONDs) were analyzed for 27 cytokines and chemokines using a multiplex bead array. We also checked whether the altered cytokine/chemokine profile in the MMN group differed significantly in the presence or absence of abnormal electrophysiological findings. RESULTS: Serum IL-1Ra, IL-2, G-CSF, TNF-alpha, and TNFR1 levels were significantly higher in the MMN group than in the ONDs group. Of these, G-CSF and TNF-alpha also showed significant increases compared to the ALS group. Serum G-CSF and TNF-alpha levels were significantly higher in MMN patients presenting with focal demyelination including conduction block than in patients without any focal demyelination. CONCLUSIONS: Proinflammatory cytokines may contribute to peripheral nerve demyelination in MMN. PMID- 25130930 TI - Polymyositis in solid organ transplant recipients receiving tacrolimus. AB - Tacrolimus, also known as FK506, is an immunosuppressive agent widely used for the prevention of acute allograft rejection in organ transplantation and for the treatment of immunological diseases. This study reports two male patients who underwent solid organ transplantation (liver and kidney). After transplant, the patients received continuous immunosuppressive therapy with oral tacrolimus and later presented clinical manifestations and laboratory signs of myopathy. Muscle biopsies of both patients clearly documented an inflammatory myopathy with the histological features of polymyositis including CD8+ T cells which invaded healthy muscle fibers and expressed granzyme B and perforin, many CD68+ macrophages and MHC class I antigen upregulation on the surface of most fibers. Because of the temporal association while receiving tacrolimus and since other possible causes for myopathy were excluded, the most likely cause of polymyositis in our patients was tacrolimus toxicity. We suggest that patients on tacrolimus should be carefully monitored for serum CK levels and clinical signs of muscle disease. PMID- 25130931 TI - Synthesis of octitols and the respective amino-derivatives from 'organo-aldols'. AB - Two diastereoisomeric keto-octoses, obtained in the reaction of 2,3:4,5-diacetone D-arabinose with protected dihydroxyacetone catalyzed with L- or D-proline, were converted into octitols by stereoselective reduction of the carbonyl group with zinc borohydride and final deprotection. The study on the preparation of the respective amino-derivatives by reductive amination of these organo-adducts is presented; stereochemical aspects of these processes are discussed. PMID- 25130933 TI - Safe storage of radical initiators within a polyaromatic nanocapsule. AB - 2,2'-Azobisisobutyronitrile and its derivatives are standard reagents for polymer and organic syntheses that generate radical species on stimuli by light or heat. Radical initiators like the azo compounds are unstable so that they should be kept in the dark at low temperature to avoid photochemical and thermal decomposition as well as accidental explosion. Here we report the spontaneous and quantitative encapsulation of the radical initiators by a supramolecular nanocapsule in aqueous solution. We demonstrate the remarkable stability of the initiators toward light and heat in the well-defined cavity shielded by the polyaromatic capsule shell. The incarcerated and stabilized initiators can be directly utilized for the radical polymerization of olefins on spontaneous release of the initiators from the capsule under the reaction conditions. PMID- 25130932 TI - The visual system in eyelid myoclonia with absences. AB - OBJECTIVE: To investigate the functional and structural brain correlates of eyelid myoclonus and absence seizures triggered by eye closure (eye closure sensitivity [ECS]). METHODS: Fifteen patients with eyelid myoclonus with absences (EMA, Jeavons syndrome), 14 patients with idiopathic generalized epilepsies (IGE) without ECS, and 16 healthy controls (HC) underwent an electroencephalography (EEG)-correlated functional magnetic resonance imaging (fMRI) and voxel brain morphometry (VBM) protocol. The functional study consisted of 30-second epochs of eyes-open and eyes-closed conditions. The following EEG events were marked and the relative fMRI maps obtained: (1) eye closure times, (2) spontaneous blinking, and (3) spontaneous and eye closure-triggered spike and wave discharges (SWD; for EMA and IGE). Within-group and between-groups comparisons were performed for fMRI and VBM data as appropriate. RESULTS: In EMA compared to HC and IGE we found: (1) higher blood oxygenation level-dependent (BOLD) signal related to the eye closure over the visual cortex, the posterior thalamus, and the network implicated in the motor control of eye closure, saccades, and eye pursuit movements; and (2) increments in the gray matter concentration at the visual cortex and thalamic pulvinar, whereas decrements were observed at the bilateral frontal eye field area. No BOLD differences were detected when comparing SWD in EMA and IGE. INTERPRETATION: Results demonstrated altered anatomo-functional properties of the visual system in EMA. These abnormalities involve a circuit encompassing the occipital cortex and the cortical/subcortical systems physiologically involved in the motor control of eye closure and eye movements. Our work supports EMA as an epileptic condition with distinctive features and provides a contribution to its classification among epileptic syndromes. PMID- 25130934 TI - Patulin reduction in apple juice by inactivated Alicyclobacillus spp. AB - This study aimed to investigate the reduction of patulin (PAT) in apple juice by 12 inactivated Alicyclobacillus strains. The reduction rate of PAT by each strain was determined by high-performance liquid chromatography (HPLC). The results indicated that the removal of PAT was strain specific. Alicyclobacillus acidoterrestris 92 and A. acidoterrestris 96 were the most effective ones among the 12 tested strains in the removal of PAT. Therefore, these two strains were selected to study the effects of incubation time, initial PAT concentration and bacteria powder amount on PAT removal abilities of Alicyclobacillus. The highest PAT reduction rates of 88.8 and 81.6% were achieved after 24-h incubation with initial PAT concentration of 100 MUg l(-1) and bacteria powder amount of 40 g l( 1) , respectively. Moreover, it was found that the treatment by these 12 inactivated Alicyclobacillus strains had no negative effect on the quality parameters of apple juice. Similar assays were performed in supermarket apple juice, where inactivated Alicyclobacillus cells could efficiently reduce PAT content. Taken together, these data suggest the possible application of this strategy as a means to detoxify PAT-contaminated juices. SIGNIFICANCE AND IMPACT OF THE STUDY: Inactivated Alicyclobacillus cells can efficiently reduce patulin concentration in apple juice. It provides a theoretical foundation for recycling of Alicyclobacillus cells from spoiled apple juice to reduce the source of pollution and the cost of juice industry. This is the first report on the use of Alicyclobacillus to remove patulin from apple juice. PMID- 25130935 TI - RBC alloimmunization and double alloantibodies in thalassemic patients. AB - PURPOSE: Alloimmunization is a common consequence of chronic blood transfusion. Double alloantibody production may complicate the condition of such patients especially for finding matched blood. In this study, we evaluated the frequency of alloantibodies in thalassemic patients with previous history of transfusion reactions. SAMPLES AND METHODS: This study was performed on 441 multiply transfused thalassemia patients Antibody screening test was carried out using three cell-panel by gel method. Positive patients were followed up for antibody identification using 11-cell panel. Direct combs' test was performed to detect auto antibodies. RESULTS: In a total of 441 cases (362 thalassemia major and 79 intermedia), 234 were males (53.1%) and 207 females (46.9%); mean age 22 years, range 3-61 years. Alloimmunization was detected in 50(11.3%) patients, including 37(74%) patients with one alloantibody, 8(16%) with two antibodies, 4(8%) patients with unknown antibodies and one patient (2%) with autoantibody. The most common alloantibodies were anti-Rh antibodies (-E/e/C/c/Cw) (26%), anti-K (28%), anti-D (16%), and anti-Colton (4%). Double antibodies were detected in eight out of 50 patients, including: Anti-D+anti-C (8%), anti-D+anti-E (2%), anti-Kell+anti D (2%), and anti-Kell+KPa (2%). A significant association was observed between the transfusion reaction history and the alloantibody detection results (p < 0.05). CONCLUSION: Antibody production against RBC antigens makes hard condition in regular blood transfusion. Double antibodies production may more complicate this situation. Thus, it is advisable to phenotype patients and matches the red cells in multiply transfused thalassemia patients. PMID- 25130936 TI - A population-based study of incidence, risk factors, clinical spectrum, and outcomes of ischemic colitis. AB - BACKGROUND & AIMS: Little is known about progression of ischemic colitis (IC) among unselected patients. We aimed to estimate the incidence, risk factors, and natural history of IC in a population-based cohort in Olmsted County, Minnesota. METHODS: We performed a retrospective population-based cohort and nested case control study of IC. Each IC case was matched to 2 controls from the same population on the basis of sex, age, and closest registration number. Conditional logistic regression, the Kaplan-Meier method, and proportional hazards regression were used to assess comorbidities, estimate survival, and identify characteristics associated with survival, respectively. RESULTS: Four hundred forty-five county residents (median age, 71.6 years; 67% female) were diagnosed with IC from 1976 through 2009 and were matched with 890 controls. The age adjusted and sex-adjusted incidence rates of IC nearly quadrupled from 6.1 cases/100,000 person-years in 1976-1980 to 22.9/100,000 in 2005-2009. The odds for IC were significantly higher among subjects with atherosclerotic diseases; odds ratios ranged from 2.6 for individuals with coronary disease to 7.9 for individuals with peripheral vascular disease. Of IC cases, 59% survived for 5 years (95% confidence interval, 54%-64%), compared with 90% of controls (95% confidence interval, 88%-92%). Age >40 years, male sex, right-sided colon involvement, concomitant small bowel involvement, and chronic obstructive pulmonary disease were all independently associated with mortality (P < .05). CONCLUSIONS: The incidence of IC increased during the past 3 decades in a population-based cohort in Minnesota. IC typically presents in older patients with multiple comorbidities and is associated with high in-hospital mortality (11.5%) and rates of surgery (17%). PMID- 25130938 TI - What gastroenterologists should know about testing patients with eosinophilic esophagitis for food allergies. PMID- 25130939 TI - Outcomes of children after esophagogastroduodenoscopy for chronic abdominal pain. PMID- 25130937 TI - Long-term use of antibiotics and proton pump inhibitors predict development of infections in patients with cirrhosis. AB - BACKGROUND & AIMS: Bacterial infections, particularly repeated infections, are significant causes of morbidity and mortality among patients with cirrhosis. We investigated and characterized risk factors for repeat infections in these patients. METHODS: In a prospective study, we collected data from 188 patients hospitalized with cirrhosis and infections and enrolled in the North American Consortium for the Study of End-Stage Liver Disease (12 centers). Patients were followed up for 6 months after hospital discharge and data were analyzed on type of infections and factors associated with subsequent infections. RESULTS: Six months after hospital discharge, 14% of subjects had received liver transplants, 27% died, and 59% were alive without liver transplantation. After discharge, 45% had subsequent infections, but only 26% of the subsequent infections occurred at the same site. Compared with patients not re-infected, patients with repeat infections were older and a higher proportion used proton pump inhibitors (PPIs) (P = .006), rifaximin (P < .001), or prophylactic therapy for spontaneous bacterial peritonitis (SBP) (P < .001). Logistic regression showed that SBP prophylaxis (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.56-7.63), PPI use (OR, 2.94; 95% CI, 1.39-6.20), SBP at hospital admission (OR, 0.37; 95% CI, 0.15-0.91), and age (OR, 1.06; 95% CI, 1.02-1.11) were independent predictors of subsequent infections. CONCLUSIONS: Patients hospitalized with cirrhosis and infections are at high risk for subsequent infections, mostly at different sites, within 6 months of index infection resolution. Those at highest risk include previously infected older patients receiving PPIs and/or SBP prophylaxis, although these associations do not prove that these factors cause the infections. New strategies are needed to prevent infections in patients with cirrhosis. PMID- 25130941 TI - COSAN as a molecular imaging platform: synthesis and "in vivo" imaging. AB - A labelling method for the covalent attachment of radioiodine to the boron-rich 8 I-cobaltabisdicarbollide (I-COSAN) and a bi-functional (iodine and PEG) COSAN derivative, [3,3'-Co(8-I-1,2-C2B9H10)(8'-(OCH2CH2)2COOC6H5-1',2'-C2B9H10)], is reported. Biodistribution studies in rodents using dissection/gamma counting and in vivo nuclear imaging have been performed. The general strategy reported here can be applied in the future to COSAN derivatives bearing a wide range of functionalities. PMID- 25130940 TI - Cerebral venous thrombosis after embolization of pediatric AVM with jugular bulb stenosis or occlusion: management and prevention. AB - PURPOSE: Thrombosis of cerebral arteriovenous malformation after embolization is rare, but can involve the normal venous network with extensive venous thrombosis. We report angioarchitecture findings, our management and prevention strategy for this complication in pediatric AVMs. METHODS: In this 5.5-year retrospective series, we reviewed records of 13 patients under 15 years who were anticoagulated after embolization. In our initial experience 4 children who didn't receive any prophylactic anticoagulation presented with extensive venous thrombosis after embolization (group 1). Following this, nine children with similar angioarchitecture and embolization modalities were treated with prophylactic anticoagulation immediately after embolization (group 2). We analyzed the type of AVM, angioarchitecture, dose of prophylactic anticoagulant, efficacy/complications of treatment and late outcome. RESULTS: All patients in group 1 had severe jugular bulb stenosis/occlusion associated with cerebral venous dilatation. In group 2 with similar angioarchitecture, only three patients (33%) developed extensive thrombosis. In both groups, thrombosis occurred within two days of treatment in six children and two weeks in one child. The diagnosis was suspected on intracranial hypertension in five patients and occulomotor disorder in one. One was asymptomatic. All children were treated with therapeutic doses of LMWH (anti-Xa: 0.5-1). No hemorrhagic complications occurred. Good venous remodeling was observed in all but one patient. CONCLUSION: Anticoagulation in extensive venous thrombosis after AVM embolization in children appears to be safe and effective. In cases with angioarchitectural features of dilatation of the cerebral venous network and occlusion/severe stenosis of the jugular bulbs, full dose anticoagulation may be required to prevent thrombosis. PMID- 25130942 TI - Tracheal rupture in complicated delivery: a case report and review of the literature. AB - A case of distal tracheal rupture is described, literature review reveals two previously reported cases of neonatal distal tracheal rupture, as well as 14 cases of anterior subglottic rupture. All patients had shoulder dystocia, and 59% had associated brachial plexus injury. Delayed diagnosis (>3 days) was common in the distal tracheal group (66%), compared to 0% in the anterior subglottic group. The 2 distal tracheal rupture patients were initially managed conservatively, but ultimately required open repair. Distal tracheal rupture is exceedingly rare and more difficult to diagnose and manage than the more common anterior subglottic rupture. PMID- 25130943 TI - Letter to the Editor regarding "In reference to the value of resident presentations at scientific meetings". PMID- 25130944 TI - Letter to the Editor regarding "Otoacoustic emissions in newborn hearing screening: a systematic review of the effects of different protocols on test outcomes". PMID- 25130945 TI - Intra-thyroidal hemangioma--a rare congenital anomaly: case presentation and literature review. AB - Infantile hemangiomas (IH) present and evolve in a predictable way. In certain cases, however, they can be of clinical significance. IHs in the airway can cause significant respiratory distress. We present the first reported case of an intrathyroidal hemangioma to cause significant respiratory distress, which was successfully treated with propranolol and dexamethasone. A review of the literature was also performed. PMID- 25130946 TI - Velopharyngeal dysfunction in children with Prader-Willi syndrome after adenotonsillectomy. AB - INTRODUCTION: Prader-Willi syndrome (PWS) is a rare genetic disorder with an incidence rate of 1 in 10,000-30,000. Patients with PWS typically have symptoms related to hypotonia, obesity, and hypothalamic dysfunction. A high rate of obstructive sleep apnea (OSA) is found among this population of patients. Adenotonsillectomy has been advocated as a first line approach for treatment of OSA in patients with PWS. Velopharyngeal dysfunction (VPD) is a known complication of adenotonsillectomy. VPD can also be present in patients with global hypotonia, such as those with PWS. The objective of this study is to review the occurrence of VPD in patients with PWS after adenotonsillectomy for OSA. METHODS: A retrospective review was performed of all patients with PWS and OSA from a tertiary pediatric hospital between the years of 2002 and 2012. Pre- and post-operative sleep studies and sleep disordered breathing symptoms, post operative VPD assessment by the speech-language pathologist (SLP), and VPD treatments were evaluated. RESULTS: Eleven patients (five males and six females), fitting the inclusion criteria, were identified. The age of the patient at the initial otolaryngologic evaluation ranged from 2 to 9 years. All patients underwent adenotonsillectomy for sleep disordered breathing. Four patients were diagnosed with post-operative hypernasality after assessment by a speech-language pathologist. The hypernasality ranged from mild to moderately severe. Of the four patients with hypernasality, two were found to have structural issues requiring surgery (pharyngeal flap). Both of the surgical patients experienced significant improvement in their VPD after surgery. The remaining two patients were found to have articulation error patterns that were considered more developmental in nature and both responded to speech therapy. All patients, except one, had improvement in their polysomnogram or sleep symptoms after adenotonsillectomy. However, three patients continue to require continuous positive airway pressure at night. CONCLUSION: Velopharyngeal dysfunction may occur after adenotonsillectomy in patients with Prader-Willi Syndrome. Families should be counseled of this risk and the potential need for operative intervention to correct it. PMID- 25130947 TI - Unintentional epidural injection of 88 MUg.kg(-1) of epinephrine. AB - We report the effects of 88 MUg.kg(-1) of epinephrine (1:10,000) injected into the caudal epidural space of a 42-week postconceptual age infant. No long-term neurological or cardiovascular sequelae occurred. Noninvasive cardiac output (CO) monitoring revealed increased CO, contractility, and stroke volume for about an hour, accompanied by a reduction in peripheral vascular resistance and a modest increase in pulse and blood pressure. PMID- 25130948 TI - Svelte integrated delivery system performance examined through diagnostic catheter delivery: the SPEED registry. AB - AIMS: The multi-center SPEED registry evaluated the procedural success and in hospital clinical outcomes of direct stenting with the Svelte 'all-in-one' coronary stent Integrated Delivery System (IDS) through diagnostic catheters to identify the clinical indications for which this approach is appropriately suited. METHODS & RESULTS: Forty-eight (48) patients with 54 lesions of lengths <=20 mm and RVD 2.5-3.5 mm were targeted for direct stenting through diagnostic catheters (4-6F) via radial or femoral approach. Procedural characteristics early in an investigator's experience (28 lesions) were compared with outcomes following experience (26 lesions). Procedure, device and strategy success were realized in 54 (100%), 50 (93%) and 46 (85%) lesions, respectively, with strategy success significantly related to RVD (P = 0.05), lesion location (P = 0.01), and diagnostic catheter size (P = 0.05). Significant improvement in crossing and intervention time and trends toward improvement in device and strategy success, reductions in procedure and radiation time and contrast use were observed. CONCLUSIONS: Direct stenting through diagnostic catheters via radial or femoral approach using the Svelte IDS is feasible and associated with good in-hospital outcomes. This approach offers the attractive option of assessing lesions via diagnostic catheter and, depending upon vessel anatomy and lesion morphology, continuing with ad-hoc interventional treatment using the same diagnostic catheter. Improvements in strategy success and procedural efficiencies, based on operator experience, facilitate catheter downsizing and reduce intervention time, ancillary product use and overall procedure costs. (c) 2014 Wiley Periodicals, Inc. PMID- 25130950 TI - Respiratory sinus arrhythmia in Chagas disease. AB - We applied the respiratory sinus arrhythmia (RSA) quantification algorithm to 24 hour ECG recordings of Chagas disease (ChD) patients with (G1, n=148) and without left ventricular dysfunction (LVD) (G2, n=33), and in control subjects (G0, n=28). Both ChD groups displayed a reduced RSA index; G1=299 (144-812); G2=335 (162-667), p=0.011, which was correlated with vagal indexes of heart rate variability analysis. RSA index is a marker of vagal modulation in ChD patients. PMID- 25130949 TI - The sympathetic skin response located in the penis as a predictor of the response to sertraline treatment in patients with primary premature ejaculation. AB - INTRODUCTION: The pathologic mechanisms of primary premature ejaculation (PPE) are complex and multifactorial, and hyperactivity of the sympathetic nervous system is one of the mechanisms. AIM: To examine the effects of sertraline on sympathetic nervous system activity and assess the predictive value of the sympathetic skin response located in the penis (PSSR) on the response to sertraline treatment in PPE patients. METHODS: Sixty-one patients with PPE were recruited. Each received 50 mg sertraline daily for 8 weeks. Before and after the experiment, the patients were evaluated for PSSR tests and sexual performance parameters. Additionally, based on the latency of PSSR, we divided the patients into a normal PSSR group and an abnormal PSSR group, and compared the sertraline treatment efficacy between the two groups. MAIN OUTCOME MEASURES: Changes in intravaginal ejaculation latency time (IELT) and the Chinese premature ejaculation index-5 (CIPE-5), and the latencies and amplitudes of PSSR after sertraline treatment. RESULTS: Overall, 58 (95.1%) patients completed the entire study and were analyzed. After the 8-week sertraline treatment, compared with those of pretreatment, IELT and CIPE-5 scores were significantly increased (both P < 0.001), and the amplitudes and latencies of PSSR in the PPE patients were remarkably decreased and prolonged, respectively (both P < 0.001). In addition, the changes of the latencies of PSSR were positively correlated with the increment of IELT (r = 0.375, P = 0.004). The treatment outcome was better in patients with a baseline abnormal PSSR than in those with a baseline normal PSSR (P = 0.021). CONCLUSIONS: These results suggest that clinical improvement in response to sertraline in the PPE patients, at least in part, is mediated through reducing sympathetic nervous system activity indexed by PSSR. Measurement of the PSSR appears to provide useful information for predicting treatment responses in the PPE patients. PMID- 25130951 TI - Frequency and clinical significance of respiratory isolates of non-tuberculous mycobacteria in Riyadh, Saudi Arabia. AB - BACKGROUND AND AIMS: The prevalence of pulmonary non-tuberculous mycobacteria (NTM) disease is increasing worldwide. The aim of this study was to assess the frequency and clinical significance of NTM isolated from respiratory specimens at King Abdul-Aziz Medical City-Riyadh, Saudi Arabia. METHODS: The medical records of all patients who had at least one respiratory specimen that was positive for growth of NTM between 2006 and 2012 were retrospectively reviewed. The clinical significance of the isolates was determined using the diagnostic criteria for NTM disease published by the American Thoracic Society (ATS). RESULT: A total of 380 respiratory specimens with positive culture for NTM from 142 patients were identified. Forty patients (28%) had definite pulmonary NTM disease with a mean (+/- standard deviation) age of 54 +/- 16 years, 58% were male and 50% had had underlying chronic lung disease. Mycobacterium avium complex (MAC) (n = 19, 48%) and Mycobacterium abscessus (n = 10, 25%) were the most commonly encountered NTM. The clinical manifestations of NTM lung disease are non-specific, with symptoms indistinguishable from pulmonary tuberculosis (TB). The most common radiological features of NTM lung disease were nodular bronchiectasis (45%) and fibrocavitary lesions (40%). CONCLUSIONS: Twenty-eight percent of the patients with NTM isolates met the ATS diagnostic criteria for NTM lung disease. MAC and M. abscessus were the most encountered NTM isolated species that caused NTM lung disease in our population, which is a rate similar to many previous studies. PMID- 25130952 TI - Immunohistochemical staining for BRAF V600E supports the diagnosis of metanephric adenoma. PMID- 25130953 TI - Probing the topological properties of the Jackiw-Rebbi model with light. AB - The Jackiw-Rebbi model describes a one-dimensional Dirac field coupled to a soliton field and can be equivalently thought of as a model describing a Dirac field with a spatially dependent mass term. Neglecting the dynamics of the soliton field, a kink in the background soliton profile yields a topologically protected zero-energy mode for the field, which in turn leads to charge fractionalisation. We show here that the model, in the first quantised form, can be realised in a driven slow-light setup, where photons mimic the Dirac field and the soliton field can be implemented-and tuned-by adjusting optical parameters such as the atom-photon detuning. Furthermore, we discuss how the existence of the zero-mode and its topological stability can be probed naturally by studying the transmission spectrum. We conclude by analysing the robustness of our approach against possible experimental errors in engineering the Jackiw-Rebbi Hamiltonian in this optical setup. PMID- 25130954 TI - Spectral Doppler interrogation of the patent foramen ovale-a window to left heart hemodynamics. AB - Spectral Doppler interrogation of flow across a patent foramen ovale (PFO) allows recording of the instantaneous pressure gradient between left and right atrium (RA). The assessment of RA pressure using the size and collapsibility of the inferior vena cava would thus allow estimation of left atrial (LA) pressure. In this article, we illustrate the value of spectral Doppler interrogation of flow across the PFO by transthoracic echocardiography as a novel and simple tool for the assessment of LA pressure and left cardiac hemodynamics in addition to the conventional noninvasive parameters. PMID- 25130955 TI - Extraskeletal myxoid chondrosarcoma with a t(9;16)(q22;p11.2) resulting in a NR4A3-FUS fusion. AB - Extraskeletal myxoid chondrosarcoma (EMC) is a rare neoplasm characterized by rearrangement of NR4A3. A t(9;22)(q22;q12), creating a fusion protein of EWSR1 and NR4A3, has been reported as a unique, recurring translocation in most cases. Reported variant translocations have resulted in fusion of NR4A3 with three other genes: TAF15, TCF12, and TFG. We report a case of EMC in a 59-year-old man who presented with a 6-month history of an enlarging mass in the proximal right thigh. The karyotype of fresh tissue from tumor taken at incisional biopsy revealed a t(9;16)(q22;p11.2). There was no evidence of an EWSR1 rearrangement by dual-color break-apart fluorescence in situ hybridization (FISH). Dual-color FISH probes revealed fusion of NR4A3 and FUS, a member of the TET family of genes, which includes EWSR1 and TAF15. Break-apart FISH probe results confirmed rearrangement of FUS. These findings show that a fusion product of FUS and NR4A3 may be an additional pathway to development of EMC. PMID- 25130956 TI - Association of sociodemographic factors and prostate-specific antigen (PSA) testing. AB - OBJECTIVES: There are conflicting recommendations regarding the use of prostate specific antigen (PSA) as a screening test. Integral to this debate is an understanding of who is currently being tested. The purpose of this study was to provide a detailed account of PSA testing practices in a major Canadian city (Calgary, Alberta) and to identify variables that may affect access to the PSA test. DESIGN AND METHODS: PSA test counts were retrieved from Calgary Laboratory Services' Laboratory Information System from January 1, 2011 to December 31, 2011. A total of 75,914 individual PSA tests were included in our analysis. The frequency of PSA testing was plotted onto a dissemination area map of Calgary using ArcGIS software. Associations with sociodemographic variables were tested using Poisson regression. RESULTS: The median PSA value was 0.93 MUg/L and the median age at collection was 58 years. Forty-three percent of men aged 60-69 received a PSA test. Visible minority status 'Black' (P=0.0002) and Metis status (P=0.0075) were associated with lower PSA testing frequencies, while median household income (P=<0.0001) and university education (P=<0.0001) were associated with higher PSA testing frequencies. CONCLUSION: There are areas in Calgary which are significantly over or under tested relative to the mean. The amount of PSA testing in men <50 years of age is increasing, which is contrary to PSA testing guidelines. PMID- 25130957 TI - Evaluation of Beckman Coulter DxI 800 immunoassay system using clinically oriented performance goals. AB - OBJECTIVES: We evaluated the analytical performance of 24 immunoassays using the Beckman Coulter DxI 800 immunoassay systems at Mayo Clinic, Rochester, MN for trueness, precision, detection limits, linearity, and consistency (across instruments and reagent lots). METHODS: Clinically oriented performance goals were defined using the following methods: trueness-published desirable accuracy limits, precision-published desirable biologic variation; detection limits - 0.1 percentile of patient test values, linearity - 50% of total error, and consistency-percentage test values crossing key decision points. Local data were collected for precision, linearity, and consistency. Data were provided by Beckman Coulter, Inc. for trueness and detection limits. RESULTS: All evaluated assays except total thyroxine were within the proposed goals for trueness. Most of the assays met the proposed goals for precision (86% of intra-assay results and 75% of inter-assay results). Five assays had more than 15% of the test results below the minimum detection limits. Carcinoembryonic antigen, total thyroxine and free triiodothyronine exceeded the proposed goals of +/-6.3%, +/-5% and +/-5.7% for dilution linearity. All evaluated assays were within the proposed goals for instrument consistency. Lot-to-lot consistency results for cortisol, ferritin and total thyroxine exceeded the proposed goals of 3.3%, 11.4% and 7% at one medical decision level, while vitamin B12 exceeded the proposed goals of 5.2% and 3.8% at two decision levels. CONCLUSIONS: The Beckman Coulter DxI 800 immunoassay system meets most of these proposed goals, even though these clinically focused performance goals represent relatively stringent limits. PMID- 25130958 TI - Biological variation of the osmolality and the osmolal gap. PMID- 25130959 TI - Validating laboratory results in a national observational cohort study without field centers: the Reasons for Geographic and Racial Differences in Stroke cohort. AB - OBJECTIVES: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is a prospective cohort of 30,239 Americans in the contiguous United States; the first of this scale to use home visits to obtain, process, and ship biologic samples to a core laboratory. Pre-analytical factors resulting from this study design may affect the results of some laboratory assays. We investigated the impact of REGARDS processing on a variety of analytes. DESIGN AND METHODS: In REGARDS, blood samples were processed in the field by technicians who were trained on standardized methods for phlebotomy and sample processing. Field processing included centrifugation using varying non-uniform equipment and shipping overnight on ice to the University of Vermont, where samples were re centrifuged for 30,000 *g-minutes and stored at -80 degrees C. We assessed the effects of REGARDS sample handling by processing split samples from 20 volunteers using either ideal procedures or simulated REGARDS procedures. Assays for 19 analytes for potential study in REGARDS were then run on both samples and results compared. RESULTS: Spearman correlation coefficients for analytes measured in ideal versus REGARDS processed samples ranged from 0.11 to 1.0. Thirteen of 19 analytes were highly correlated (>0.75), but platelet proteins were more variable. CONCLUSIONS: Simulation of non-optimal field processing and shipment to a central laboratory showed high variability in analytes released by platelets. The majority of other analytes produced valid results, but platelet contamination in REGARDS samples makes measurement of platelet proteins unadvisable in these samples. Future analytes considered by REGARDS or similar studies should undergo similar pilot testing. PMID- 25130961 TI - Plantar pressure characteristics in hallux valgus feet. AB - Due to the pathoanatomical changes in hallux valgus feet, the plantar flexion moment of the first metatarsophalangeal joint is reduced. Therefore, load bearing of the hallux is decreased during push-off. We assessed loading parameters in hallux valgus feet. Based on dorsal-plantar weight bearing radiographs of 61 feet, the intermetatarsal-, hallux valgus-, distal metatarsal articulation-angle, and sesamoid position were evaluated. Plantar pressure assessment was performed with the emed(r) system during level walking. We found negative correlations between hallux valgus angle and peak pressure in the great toe (r=-0.301, p<0.023), the maximum force of the hallux (r=-0.481, p<0.001), and contact time of the great toe (r=-0.448, p<0.001), and positive correlations for force time integral (r=0.348, p<0.001), contact area (r=0.307, p<0.020), maximum force (r=0.430, p<0.001), and peak pressure (r=0.361, p<0.006) of the fifth metatarsal head. A positive correlation between the sesamoid and the metatarsal subluxation regarding maximum force (r=0.294, p<0.034), and a negative correlation between the contact area of the hallux (r=-0.232, p<0.020) was shown. Depending on the severity, hallux valgus angle, and sesamoid subluxation, load shows significant lateral transmission in hallux valgus feet. PMID- 25130960 TI - Is preoperative radiotherapy suitable for all patients with primary soft tissue sarcoma of the limbs? AB - AIM: To evaluate the indications and results of preoperative radiotherapy (RT) on a series of selected patients treated at our institution with curative intent for a limb sarcoma (STS). PATIENTS AND METHODS: From 05/1993 to 12/2011, 64 STS patients received preoperative RT. RESULTS: RT was delivered as a "limb salvage treatment" prior to surgery for the following reasons: as the preferential induction treatment in 53 patients (83%) or as a second intent (17%) after the failure of neoadjuvant systemic chemotherapy/isolated limb perfusion. Surgery was performed after RT in 54 (84%) patients and final limb salvage was performed in 98%. Musculo-cutaneous flap reconstruction was planned upfront in 44% patients, and 19% had a skin graft. Seven patients (13%) had a postoperative RT boost. Thirteen (20%) patients had grade (G) 3/4 adverse events, one after RT and 12 after surgery. At a median follow-up of 3.5 years, the 3-year actuarial overall survival (OS) and distant relapse (DR) rates were 83% and 31%, respectively. Two patients developed a local relapse and two a local progression (non-operated patients). In the multivariate analysis (MVA), histological subtype (leiomyosarcoma) and grade 3 were predictive of poorer survival. Patients with >3 month delay between the start of RT and surgery at our institution had an increased risk of DR in the MVA. CONCLUSION: Induction RT should be personalised according to histological subtype, tumour site and risks-benefit ratio of preoperative radiotherapy and is best managed by a multidisciplinary surgical and oncology team in a specialist sarcoma centre. PMID- 25130962 TI - Routine assessment of psychosocial problems after cancer genetic counseling: results from a randomized controlled trial. AB - Approximately 70% of counselees undergoing cancer genetic counseling and testing (CGCT) experience some degree of CGCT-related psychosocial problems. We evaluated the efficacy of an intervention designed to increase detection and management of problems 4 weeks after completion of CGCT. In this randomized, controlled trial, 118 participants completed a CGCT-related problem questionnaire prior to an - audiotaped - telephone session with their counselor 1 month after DNA-test disclosure. For those randomized to the intervention group (n = 63), a summary of the questionnaire results was provided to the counselor prior to the telephone session. Primary outcomes were discussion of the problems, counselors' awareness of problems, and problem management. Secondary outcomes included self-reported distress, cancer worries, CGCT-related problems, and satisfaction. Counselors who received a summary of the questionnaire were more aware of counselees' problems in only one psychosocial domain (practical issues). No significant differences in the number of problems discussed, in problem management, or on any of the secondary outcomes were observed. The prevalence of problems was generally low. The telephone session, combined with feedback on psychosocial problems, has minimal impact. The low prevalence of psychosocial problems 1 month post-CGCT recommends against its use as a routine extension of the CGCT procedure. PMID- 25130963 TI - [Down-regulated betaIII-tubulin expression can reverse paclitaxel resistance in A549/taxol cells lines]. AB - BACKGROUND: Chemotherapy drug resistance is the primary causes of death in patients with pulmonary carcinoma which make tumor recurrence or metastasis. beta tubulin is the main cell targets of anti-microtubule drug. Increased expression of betaIII-tubulin has been implicated in non-small cell lung cancer (NSCLC) cell lines. To explore the relationship among the expression level of betaIII-tubulin and the sensitivity of A549/Taxolcell lines to Taxol and cell cycles and cell apoptosis by RNA interference-mediated inhibition of betaIII-tubulin in A549/Taxol cells. METHODS: Three pairs of siRNA targetd betaIII-tubulin were designed and prepared, which were transfected into A549/Taxol cells using LipofectamineTM 2000. We detected the expression of betaIII-tubulin mRNA using Real-time fluorescence qRT-PCR. Tedhen we selected the most efficient siRNA by the expression of betaIII-tubulin mRNA in transfected group. betaIII-tubulin protein level were mesured by Western blot. The taxol sensitivity in transfected group were evaluated by MTT assay. And the cell apoptosis and cell cycles were determined by flow cytometry. RESULTS: betaIII-tubulin mRNA levels in A549/Taxol cells were significantly decreased in transfected grop by Real-time qRT-PCR than control groups. And betaIII-tubulin siRNA-1 sequence showed the highest transfection efficiency, which was (87.73+/-4.87)% (P<0.01); Western blot results showed that the expressional level of BIII tublin protein was significantly down reulated in the transfectant cells than thant in the control cells. By MTT assay, we showed that the inhibition ratio of Taxol to A549/Taxol cells transfeced was higher than that of control group (51.77+/-4.60)% (P<0.01). The early apoptosis rate of A549/Taxol cells in transfected group were significantly higher than that of control group (P<0.01); G2-M content in taxol group obviously increased than untreated samples by the cell cycle (P<0.05). CONCLUSIONS: betaIII-tubulin down regulated significantly sensitized NSCLC A549/Taxol cells to Paclitaxel. PMID- 25130964 TI - [Multi-factor retrospective study in 91 small cell lung cancer patients]. AB - BACKGROUND: Small cell lung cancer accounts for about 15%-25% of lung cancer, although the new chemotherapy drugs and radiation technology are continuously progressing, but the prognosis is still poor. To explore the prognostic factor of small cell lung cancer (SCLC), we study the correlation between effect, prognosis and TNM stage, various treatment mode. METHODS: We collected 91 Limited-disease SCLC patients' data From 2006 to 2012. The data were reviewed retrospectively and restaged as I, II, IIIa and IIIb stage groups according to the clinical staging in the seventh edition of the tumor. We compare the progression-free survival (FPS) and overall survival (OS). Survival analysis was evaluated by Kaplan-Meier and multivariate analysis was performed by Cox proportional hazards model. RESULTS: In the whole group, patients achieved complete response and partial response, exhibited an RR of 93.4%. The median PFS was 14.25 months of which, 22.03 months in patients in stage I, 15.97 months in stage II, 11.99 months in stage IIIa and 10.5 months in stage IIIb (P<0.05). The median overall survival (OS) was 19.56 months of which, 33.38 months in patients in stage I, 22.07 months in stage II, 16.0 months in stage IIIa and 15.52 months in stage IIIb (P<0.05). Patients of stage IIIa and IIIb have longer survival time in earlier radiation groups then that of later radiation groups. Univariate analysis indicate stage of TNM, the pattern of radiation therapy and chemotherapy cycles before radiation therapy were significantly related to the survival in SCLC. Multivariate analysis showed that stage of TNM, ECOG (Eastern Cooperative Oncology Group) performance status, pattern of radiation therapy and cycle numbers of chemotherapy before radiation were factors correlated with survival. CONCLUSIONS: The stage of TNM may become beneficial prognostic factors in the treatment of LD-SCLC. The time of radiation therapy in stage IIIa and IIIb is of worth further investigation. PMID- 25130965 TI - [Postoperative complications of bilobectomy compared with lobectomy in the right lung of non-small cell lung cancer patients]. AB - BACKGROUND: The mismatch between pleural space and remnant lung after bilobectomy has been considered as the main reason for the high incidence of postoperative complications in non-small cell lung cancer (NSCLC) patients. The aim of this study is to analyze the differences in postoperative complications between bilobectomy and lobectomy in the right lung of NSCLC patients. METHODS: This study included 528 NSCLC patients who underwent right pulmonary lobectomy. A total of 352 cases that underwent upper or lower right lobectomy (108 upper and 244 lower) were the control group, and 176 cases that underwent bilobectomy (57 upper and middle and 119 lower and middle) were the observation group. A retrospective case-control study was performed on a series of matched NSCLC patients. Cases and controls were matched by age, ppoFEV1%, LEVF%, operation method, cardiac comorbidity, type of postoperative management, and pathological type at a ratio of 1:2. The prevalence of 30-day death, occurrence of cardiac respiratory complications (hospital-acquired pneumonia, low oxygen concentration, pulmonary embolism, cerebral apoplexy, arrhythmia, myocardial ischemia or infarction, and cardiac insufficiency) and occurrence of space-related complications (atelectasis, air leak more than 5 days, and pneumothorax) were compared between the bilobectomy and lobectomy groups. RESULTS: The prevalence of 30-day death was 3.4% (6/176) in the bilobectomy group and 2.3% (8/352) in the lobectomy group. No statistical significance was observed between the two groups. The cardiac-respiratory complication rate in bilobectomy group (23.8%; 42/176) was higher than that in lobectomy group (10.7%; 38/352). The cardiac-respiratory complication rate of the lower and middle pulmonary lobectomy patients in the bilobectomy group (26.5%; 31/119) was significantly higher than that in the lower pulmonary lobectomy patients (4.9%; 12/244). The space-related complications in bilobectomy group and lobectomy group were 20.4% (36/176) and 17.3% (61/352), respectively. No statistically significant difference between the two groups was observed. CONCLUSIONS: The postoperative cardiac-respiratory complications of NSCLC patients with right bilobectomy are higher than those of the right lobectomy patients, but the prevalence of 30-day death and space-related complication was not statistically different between the two groups. PMID- 25130966 TI - [A meta-analysis of Association between MGMT gene promoter methylation and non small cell lung cancer]. AB - BACKGROUND: DNA promoter methylation of the tumor suppressor genes was one of the key mechanism for gene silence. The aim of this study is to investigate the difference of MGMT gene promoter methylation rate in tumor tissue and autologous controls (serum, normal lung tissue and bronchial lavage fluid) in patients with non-small cell lung cancer (NSCLC). METHODS: The databases of Medline, EMBSE, CNKI and Wanfang were searched for selection of published articles of MGMT gene promoter methylation and non-small cell lung carcinoma risk. The pooled odds ratio (OR) and percentage of MGMT for lung cancer tissue of NSCLC patients compared with normal lung tissue, plasma and the bronchial lavage fluid were pooled. RESULTS: 15 articles of association between MGMT gene promoter methylation and non small cell lung carcinoma risk were included in this meta analysis. The combined results demonstrated the methylation rate of MGMT in NSCLC cancer tissue was 38% (95%CI: 23%-53%). For normal lung tissue, plasma and the bronchial lavage fluid were 16% (95%CI: 5%-27%), 23% (95%CI: 10%-34%) and 39% (95%CI: 23%-55%) respectively. The OR in cancer tissue was much higher than that in normal lung tissue and plasma odds ratio (OR) 3.98 (95%CI: 2.71-5.84, P<0.05) and OR 1.88 (95%CI: 1.16-3.05, P<0.05), but not in bronchial lavage fluid OR 2.05 (95%CI: 0.88-4.78, P>0.05). CONCLUSIONS: Mehtylation rate in MGMT gene promoter of cancer tissue in NSCLC patients was much higher than that in normal lung tissue and plasma, which showed a close association between NSCLC cancer and MGMT gene promoter methylation. PMID- 25130967 TI - [A comparison of direct sequencing and ARMS assay performance in EGFR mutation analysis of non-small cell lung cancer patients]. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are mainly used for the targeted therapy of non-small cell lung cancer (NSCLC). Therefore, EGFR mutations should be detected to treat lung cancer. The aim of this study is to determine the detection rate of NSCLC in patients with EGFR gene mutations by conducting direct sequencing and ARMS assay. METHODS: A total of 451 patients who were diagnosed with NSCLC between April 2012 and June 2013 participated in this study. Gene mutation was detected in the exon of EGFR 18 to 21 by direct sequencing and ARMS assay. RESULTS: All of the 451 cases of NSCLC were subjected to direct sequencing and ARMS assay. Using both techniques, we detected the same EGFR mutation in 127 cases and different EGFR mutations in 5 cases, but no mutations were detected in 186 cases. In direct sequencing alone, EGFR mutation was detected in 50 cases. In ARMS assay alone, EGFR mutation was detected in 83 cases. The mutation rates of direct sequencing and ARMS assay were 40.4% and 47.7%, respectively. Therefore, the mutation detection rate of ARMS assay was significantly higher than that of direct sequencing (P<0.001). In 204 paraffin tissue samples of NSCLC, the mutation detection rate of ARMS assay (59.80%) was significantly higher than that of direct sequencing (41.67%; P<0.001). By comparison, the mutation detection rates of ARMS assay (39.58%) and direct sequencing (38.33%) showed no significant difference (P=0.083) when 240 fresh tissue samples of NSCLC were used. CONCLUSIONS: Direct sequencing and ARMS assay exhibited similar efficacy in detecting EGFR mutations. Despite its high operational costs, ARMS assay was more sensitive and more convenient than direct sequencing, particularly when a small number of tissues were used. By comparison, direct sequencing could detect mutations that were not detected by ARMS assay. Therefore, the combination of direct sequencing and ARMS assay could provide more reliable and comprehensive test results than the lone application of each technique. PMID- 25130968 TI - [Association of genetic polymorphisms in IL-6 and IL-1beta gene with risk of lung cancer in female non-smokers]. AB - BACKGROUND: Interleukin-6 (IL-6) and interleukin-1beta (IL-1beta), known as multifunctional cytokines with high biological activity, play an important role in physiological and pathological responses such as inflammation, immune response and even tumors. There have been multiple polymorphism loci found in IL-6 gene and IL-1beta gene. The aim of this study is to investigate the relationship between IL-6-643 (C/G) and IL-1beta-31 (C/T) polymorphisms and lung cancer risk among female non-smokers and explore the interaction effects on lung cancer risk between this two polymorphisms and potential risk factors such as cooking oil fumes exposure and history of tuberculosis. METHODS: We performed a case-control study using 363 female lung cancer patients as cases and 370 healthy volunteers as controls. Genomic DNA was extracted from peripheral blood samples using classical phenol chloroform method. The genotyping of IL-6-634 or IL-1beta-31 polymorphisms was performed using Taqman real time PCR technique by ABI7500. Two sided chi2 test was used to compare the distribution of the genotypes and risk factors between cases and controls. Unconditional Logistic regression analysis was performed to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) for estimating the association between certain genotypes and lung cancer and exploring the interaction of risk factors and genetic polymorphisms. RESULTS: The risk of lung cancer was significantly higher in those with IL-6-634 CG genotype than those with CC genotype (OR=1.61, 95%CI: 1.19-2.19, P=0.002). The CG or GG genotype carriers had an elevated risk of lung cancer than CC genotype carriers (OR=1.48, 95%CI: 1.10-1.98, P=0.01). No significant association was observed between IL-1beta-31 gene polymorphism and lung cancer risk. Compared with IL-6-634 CC genotype carriers with no cooking oil fumes exposure, a significant higher risk was found in individuals who were CG or GG genotype carriers with exposure to cooking oil fumes (OR=2.45, 95%CI: 1.54-3.90). Compared with IL-6-634 CC genotype carriers with no history of tuberculosis, a significant elevated risk was found in individuals who were CG or GG genotype carriers with history of tuberculosis (OR=2.44, 95%CI: 1.05-5.66). CONCLUSIONS: Our results indicated that IL-6-634 polymorphism was associated with the risk of lung cancer risk in female non-smokers. Individuals with both IL-6-634 CG or GG genotype and exposure to cooking oil fumes had a higher risk of lung cancer. Also individuals with both IL-6-634 CG or GG genotype and history of tuberculosis had an elevated risk of lung cancer. PMID- 25130969 TI - [Research status on molecular targeted therapy for squamous-cell lung cancer]. AB - Lung cancer is one of the world's highest morbidity and mortality disease in malignant tumors currently. Squamous-cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, after surgery, radiotherapy, chemotherapy and other comprehensive treatment, its 5-year survival rate is still below 15%. The current molecular targeted therapy plays an important role in the treatment of SQCLC, an urgent need to be more in-depth study. SQCLC molecular targeted therapy mainly epidermal growth factor receptor (EGFR), phosphoin-3 kinase catalytic alpha polypeptide (PIK3CA), fibroblast growth factor receptor 1 (FGFR1), discoidin domain receptor 2 (DDR2), phosphatase and tensin homolog deleted on chromosome ten (PTEN), BRAF, MET, insulin-like growth factor 1 receptor (IGF-1R) and other as the target of the drug, some targeted drugs are being developed, and some targeted drugs have entered clinical trials. In recent years, with studies molecular targeted therapy in SQCLC, analysis of the development and trgeted therapy achieved substantial progress in improving the survival rate of SQCLC, and other research to improve the quality of life, make is possible to individualized targeted therapy of SQCLC. PMID- 25130970 TI - [Dysregulation of HGF/c-Met signal pathway and their targeting drugs in lung cancer]. AB - C-MET is a coding product of proto oncogene c-MET, hepatocyte growth factor (HGF) receptor with tyrosine kinase activity. The abnormal expression of c-Met gene is correlated with the tumorigenesis and development of lung cancer. Once the tyrosine kinase is activated by the interaction between the HGF ligand and the TK receptor, and the activated kinase will promote the cell proliferation, angiogenesis, invasion and metastasis of different tumors, as well as lung cancer. The targeted therapy to HGF/c-Met signal pathway is a new highlight in the treatments of lung cancer. In this review, we will discuss the dysregulation of HGF/c-Met signal pathway in lung cancer and the new progress for the targeted drugs to this pathway. PMID- 25130972 TI - The response regulator BcSkn7 is required for vegetative differentiation and adaptation to oxidative and osmotic stresses in Botrytis cinerea. AB - The high-osmolarity glycerol pathway plays an important role in the responses of fungi to various environmental stresses. Saccharomyces cerevisiae Skn7 is a response regulator in the high-osmolarity glycerol pathway, which regulates the oxidative stress response, cell cycle and cell wall biosynthesis. In this study, we characterized an Skn7 orthologue BcSkn7 in Botrytis cinerea. BcSKN7 can partly restore the growth defects of S. cerevisiae SKN7 mutant and vice versa. The BcSKN7 mutant (DeltaBcSkn7-1) revealed increased sensitivity to ionic osmotic and oxidative stresses and to ergosterol biosynthesis inhibitors. In addition, DeltaBcSkn7-1 was also impaired dramatically in conidiation and sclerotial formation. Western blot analysis showed that BcSkn7 positively regulated the phosphorylation of BcSak1 (the orthologue of S. cerevisiae Hog1) under osmotic stress, indicating that BcSkn7 is associated with the high-osmolarity glycerol pathway in B. cinerea. In contrast with BcSak1, BcSkn7 is not involved in the regulation of B. cinerea virulence. All of the phenotypic defects of DeltaBcSkn7 1 are restored by genetic complementation of the mutant with the wild-type BcSKN7. The results of this study indicate that BcSkn7 plays an important role in the regulation of vegetative differentiation and in the response to various stresses in B. cinerea. PMID- 25130973 TI - Recent advances in the evaluation of the oxygen transfer rate in oak barrels. AB - The entry of atmospheric oxygen into wine barrels is a desirable characteristic of the wine aging process. The oxygen transfer rate regulates changes in wine affecting aging rates because some barrels may undergo a greater wine oxygenation. This study measured the transfer rate and oxygen distribution within a barrel. The analysis confirmed the presence of a dissolved oxygen concentration gradient in the liquid, with greater concentrations near the bung. The study of the transfer rate of oxygen over time, in 12 barrels of different types, showed that wetting wood reduces oxygen diffusion and the oxygen transfer rate (OTR). These results are the first to determine the kinetics of oxygen entry into wine barrels and can be used to quantify the annual rate of oxygen entry into wine barrels. PMID- 25130971 TI - [Effect of PI3K/AKT pathway on cisplatin resistance in non-small cell lung cancer]. AB - Accumulating evidences indicate that aberrant activation of PI3K/AKT pathway in non-small cell lung cancer plays a vital role in tumor cell proliferation,apoptosis, and survival including drug resistance. Cisplatin as first-line chemotherapy are in widespread clinical use in patients with non-small cell lung cancer, however, the development of cisplatin resistance significantly impedes its clinic efficacy. Cisplatin resistance is a complicated process that various mechanisms participating in to interact, of which PI3K/AKT pathway keeping sustained activated is one of the most important reasons. This article reviewed the progress of research on the relationship between PI3K/AKT pathway and cisplatin resistance. PMID- 25130974 TI - Bridging the gap between metabolic liver processes and functional tissue structure by integrated spatiotemporal modeling applied to hepatic ammonia detoxification. PMID- 25130975 TI - Neurophysiological evidence for generalized sensory neuronopathy in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome. AB - INTRODUCTION: Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a recently described multisystem ataxia defined by the presence of cerebellar ataxia, bilateral vestibulopathy, and a somatosensory deficit. The characteristic clinical sign is an abnormal visually enhanced vestibuloocular reflex. The somatosensory deficit contributes to a significant level of disability in CANVAS. METHODS: This study was a neurophysiological investigation of 14 patients with CANVAS. RESULTS: Findings revealed uniformly absent sensory nerve action potentials in all limbs, abnormal blink reflexes in 13 of 14 patients, and abnormal masseter reflexes in 6 of 11 patients. Tibial H reflexes were absent in 11 of 14 patients. Somatosensory evoked potentials were abnormal in 10 of the 11 patients tested, and brainstem auditory evoked responses were abnormal in 3 of 8. Cutaneous silent period responses were abnormal in 7 of 14 patients. CONCLUSIONS: We suggest that a sensory neuronopathy should be sought in cerebellar and/or vestibular ataxias, particularly where the degree of ataxia is out of proportion to the clinically identified cerebellar and/or vestibular dysfunction. PMID- 25130977 TI - The electrode-tissue interface: the revolutionary role of steroid-elution. AB - The electrode-tissue interface is that area lying between the cathode of a low voltage implantable pacemaker or cardioverter-defibrillator (ICD) lead and the endocardium or epi-myocardium of the cardiac chamber being paced. The electrical stimulus that is delivered to this interface is responsible for myocyte depolarization with consequent cardiac contraction. The process by which this occurs is reasonably well understood and any explanation requires a basic understanding of the physics and cellular electrophysiology of pacing. The effective and efficient delivery of electrical energy to the myocardium via the lead is dependent on many factors to be discussed in this review. However, despite numerous evolutionary changes occurring in the cathode's material, design, and surface configuration, it was not until the incorporation of steroid elution to the electrode-tissue interface that reliable and significantly low stimulation threshold cardiac pacing became possible. PMID- 25130978 TI - The economic burden of pneumonia and meningitis among children less than five years old in Hanoi, Vietnam. AB - OBJECTIVE: To estimate the average treatment costs of pneumonia and meningitis among children under five years of age in a tertiary hospital in Hanoi, Vietnam from societal, health sector and household perspectives. METHODS: We used a cost of-illness approach to identify cost categories to be included for different perspectives. A prospective survey was conducted among eligible patients to get detailed personal costing items. RESULTS: From the perspective of the health sector, the mean costs for treating a case of pneumonia and meningitis were USD 180 and USD 300, respectively. From the household's perspective, the average treatment costs were USD 272 for pneumonia and USD 534 for meningitis. When also including indirect costs, the average total treatment costs from the societal perspective were USD 318 for pneumonia and USD 727 for meningitis. CONCLUSION: The study contributed to limited evidence on the high treatment costs of pneumonia and meningitis to the Vietnamese society, which is useful for a cost effectiveness analysis of Haemophilus influenzae type b vaccine or other relevant disease preventions. It also indicated a need to re-evaluate the health insurance policy for children under 6 years old, so that the unnecessarily high out-of pocket costs of these diseases are reduced. PMID- 25130979 TI - Morphological alterations in the synganglion and integument of Rhipicephalus sanguineus ticks exposed to aqueous extracts of neem leaves (Azadirachta indica A. JUSS). AB - Currently, the necessity of controlling infestation by ticks, especially by Rhipicephalus sanguineus, has led researchers and public health managers around the world to search for new and more efficient control methods. This way, we can highlight neem (Azadirachta indica A. Juss) leaf, bark, and seed extracts, which have been very effective on tick control, and moreover causing less damage to the environment and to the host. This study showed the potential of neem as a control method for R. sanguineus through morphological and morphometric evaluation of the integument and synganglion of females, in semiengorged stage. To attain this, routine techniques of optical microscopy, scanning electron microscopy and morphometry of the cuticle and subcuticle of the integument were applied. Expressive morphological alterations were observed in both organs, presenting a dose-dependent effect. Integument epithelial cells and nerve cells of the synganglion showed signs of cell vacuolation, dilated intercellular boundaries, and cellular disorganization, alterations not previously reported in studies with neem. In addition, variations in subcuticle thickness were also observed. In general, the effects of neem are multiple, and affect the morphology and physiology of target animals in various ways. The results presented in this work are the first evidence of its effects in the coating and nervous system of ticks, thus allowing an indication of neem aqueous extracts as a potential control method of the brown dog tick and opening new perspectives on acaricide use. PMID- 25130980 TI - Cryptocoryne spiralis, a substitute of Aconitum heterophyllum in the treatment of diarrhoea. AB - OBJECTIVE: To scientifically validate the traditional substitution of roots of highly expensive Aconitum heterophyllum (AH) with rhizomes of Cryptocoryne spiralis (CS) in the treatment of diarrhoea. METHODS: Different fractions from root/rhizome extract of both the plant were subjected to faecal excretion rate and castor oil-induced diarrhoea models. Further, bioactive fractions from both plants, i.e. chloroform (CAH) from AH at 50 mg/kg p.o. and ethyl acetate (EACS) from CS at 100 mg/kg p.o., were examined for small intestinal transit, intestinal fluid accumulation and PGE2 -induced enteropooling models in rats. Biochemical estimations and Na(+) and K(+) concentration in intestinal fluid were also determined along with antibacterial studies. Phytochemical standardisation of AH and CS was performed by quantifying aconitine for the former and stigmasterol for the latter using HPLC. KEY FINDINGS: CAH and EACS illustrated a significant reduction in faecal output rate and demonstrated a protection of 63.068% at CAH 50 and 59.090% at EACS 100 mg/kg p.o. in castor oil-induced diarrhoea model. The fractions also persuaded promising effects in all the other models, restored alterations in biochemical parameters and showed potential antibacterial activity. CONCLUSION: The antidiarrhoeal potential of AH and CS may be attributed to an antimotility and antisecretory type of effect. PMID- 25130981 TI - The stroke 'Act FAST' campaign: remembered but not understood? AB - BACKGROUND: The stroke awareness raising campaign 'Act FAST' (Face, Arms, Speech: Time to call Emergency Medical Services) has been rolled out in multiple waves in England, but impact on stroke recognition and response remains unclear. PURPOSE: The purpose of this study was to test whether providing knowledge of the FAST acronym through a standard Act FAST campaign leaflet increases accurate recognition and response in stroke-based scenario measures. METHODS: This is a population-based, cross-sectional survey of adults in Newcastle upon Tyne, UK, sampled using the electoral register, with individuals randomized to receive a questionnaire and Act FAST leaflet (n = 2500) or a questionnaire only (n = 2500) in 2012. Campaign message retention, stroke recognition, and response measured through 16 scenario-based vignettes were assessed. Data were analyzed in 2013. RESULTS: Questionnaire return rate was 32.3% (n = 1615). No differences were found between the leaflet and no-leaflet groups in return rate or demographics. Participants who received a leaflet showed better campaign recall (75.7% vs. 68.2%, P = 0.003) and recalled more FAST mnemonic elements (66.1% vs. 45.3% elements named correctly, P < 0.001). However, there were no between-group differences for stroke recognition and response to stroke-based scenarios (P > 0.05). CONCLUSIONS: Despite greater levels of recall of specific 'Act FAST' elements among those receiving the Act FAST leaflet, there was no impact on stroke recognition and response measures. PMID- 25130982 TI - Quantification and probabilistic modeling of CRT obsolescence for the State of Delaware. AB - The cessation of production and replacement of cathode ray tube (CRT) displays with flat screen displays have resulted in the proliferation of CRTs in the electronic waste (e-waste) recycle stream. However, due to the nature of the technology and presence of hazardous components such as lead, CRTs are the most challenging of electronic components to recycle. In the State of Delaware it is due to this challenge and the resulting expense combined with the large quantities of CRTs in the recycle stream that electronic recyclers now charge to accept Delaware's e-waste. Therefore it is imperative that the Delaware Solid Waste Authority (DSWA) understand future quantities of CRTs entering the waste stream. This study presents the results of an assessment of CRT obsolescence in the State of Delaware. A prediction model was created utilizing publicized sales data, a variety of lifespan data as well as historic Delaware CRT collection rates. Both a deterministic and a probabilistic approach using Monte Carlo Simulation (MCS) were performed to forecast rates of CRT obsolescence to be anticipated in the State of Delaware. Results indicate that the peak of CRT obsolescence in Delaware has already passed, although CRTs are anticipated to enter the waste stream likely until 2033. PMID- 25130983 TI - Macrophage induced gelsolin in response to Group B Streptococcus (GBS) infection. AB - Group B Streptococcus (GBS) has evolved several strategies to avoid host defences. We have shown that interaction of macrophages with GBS causes macrophage calpain activation, cytoskeletal disruption and apoptosis, consequences of intracellular calcium increase induced by membrane permeability alterations provoked by GBS-beta-haemolysin. Open question remains about what effect calcium influx has on other calcium-sensing proteins such as gelsolin, involved in cytoskeleton modulation and apoptosis. Therefore we analysed the effect of GBS-III-COH31:macrophage interaction on gelsolin expression. Here we demonstrate that an early macrophage response to GBS-III-COH31 is a very strong gelsolin increase, which occurs in a time- and infection-ratio-dependent manner. This is not due to transcriptional events, translation events, protein turnover alterations, or protein-kinase activation, but to calcium influx, calpain activation and caspase-3 degradation. In fact, EGTA and PD150606 (calpain inhibitor) prevented gelsolin increase while BAF (caspase inhibitor) enhanced it. Since gelsolin increase is induced by highly beta-haemolytic GBS-III-NEM316 and GBS-V-10/84, but not by weakly beta-haemolytic GBS, or GBS-III-COH31 in conditions suppressing beta-haemolysin expression/activity and the presence of dipalmitoylphosphatidylcholine (beta-haemolysin inhibitor), GBS-beta-haemolysin is solely responsible for gelsolin increase causing, through membrane permeability defects, calcium influx and calpain activation. Early gelsolin increase could represent a macrophage response to antagonize apoptosis since gelsolin knockdown increases macrophage susceptibility to GBS-induced apoptosis. This response seems to be GBS specific because macrophage apoptosis by Staurosporine or Cycloeximide does not induce gelsolin. PMID- 25130976 TI - Etiology, triggers and neurochemical circuits associated with unexpected, expected, and laboratory-induced panic attacks. AB - Panic disorder (PD) is a severe anxiety disorder that is characterized by recurrent panic attacks (PA), which can be unexpected (uPA, i.e., no clear identifiable trigger) or expected (ePA). Panic typically involves an abrupt feeling of catastrophic fear or distress accompanied by physiological symptoms such as palpitations, racing heart, thermal sensations, and sweating. Recurrent uPA and ePA can also lead to agoraphobia, where subjects with PD avoid situations that were associated with PA. Here we will review recent developments in our understanding of PD, which includes discussions on: symptoms and signs associated with uPA and ePAs; Diagnosis of PD and the new DSM-V; biological etiology such as heritability and gene*environment and gene*hormonal development interactions; comparisons between laboratory and naturally occurring uPAs and ePAs; neurochemical systems that are associated with clinical PAs (e.g. gene associations; targets for triggering or treating PAs), adaptive fear and panic response concepts in the context of new NIH RDoc approach; and finally strengths and weaknesses of translational animal models of adaptive and pathological panic states. PMID- 25130984 TI - Near-IR-triggered, remote-controlled release of metal ions: a novel strategy for caged ions. AB - A ligand incorporating a dithioethenyl moiety is cleaved into fragments which have a lower metal-ion affinity upon irradiation with low-energy red/near-IR light. The cleavage is a result of singlet oxygen generation which occurs on excitation of the photosensitizer modules. The method has many tunable factors that could make it a satisfactory caging strategy for metal ions. PMID- 25130985 TI - Laparoscopic hepatectomy is theoretically better than open hepatectomy: preparing for the 2nd International Consensus Conference on Laparoscopic Liver Resection. AB - Six years have passed since the first International Consensus Conference on Laparoscopic Liver Resection was held. This comparatively new surgical technique has evolved since then and is rapidly being adopted worldwide. We compared the theoretical differences between open and laparoscopic liver resection, using right hepatectomy as an example. We also searched the Cochrane Library using the keyword "laparoscopic liver resection." The papers retrieved through the search were reviewed, categorized, and applied to the clinical questions that will be discussed at the 2nd Consensus Conference. The laparoscopic hepatectomy procedure is more difficult to master than the open hepatectomy procedure because of the movement restrictions imposed upon us when we operate from outside the body cavity. However, good visibility of the operative field around the liver, which is located beneath the costal arch, and the magnifying provide for neat transection of the hepatic parenchyma. Another theoretical advantage is that pneumoperitoneum pressure reduces hemorrhage from the hepatic vein. The literature search turned up 67 papers, 23 of which we excluded, leaving only 44. Two randomized controlled trials (RCTs) are underway, but their results are yet to be published. Most of the studies (n = 15) concerned short-term results, with some addressing long-term results (n = 7), cost (n = 6), energy devices (n = 4), and so on. Laparoscopic hepatectomy is theoretically superior to open hepatectomy in terms of good visibility of the operative field due to the magnifying effect and reduced hemorrhage from the hepatic vein due to pneumoperitoneum pressure. However, there is as yet no evidence from previous studies to back this up in terms of short-term and long-term results. The 2nd International Consensus Conference on Laparoscopic Liver Resection will arrive at a consensus on the basis of the best available evidence, with video presentations focusing on surgical techniques and the publication of guidelines for the standardization of procedures based on the experience of experts. PMID- 25130986 TI - Surgical management of thymic epithelial tumors in children: lessons from the French Society of Pediatric Oncology and review of the literature. AB - PURPOSE: We report the results of a French multicenter retrospective study based on a period of more than 30 years and a review of the literature in order to more clearly define the surgical approach and specific pediatric risk factors. METHODS: Clinical data of children comprising all histologic subtypes of thymic epithelial tumors (TET) treated between 1979 and 2009 in French pediatric oncology centers were retrospectively analyzed and discussed in the light of a review of all pediatric cases reported in the literature. RESULTS: Nine cases were identified, corresponding to five females and four males with a median age of 13 years (range: 7.5-17). Histologic subtypes were type AB (n = 1), type B (n = 5) and type C (n = 3). Treatment consisted of tumor resection (4 R0, 4 R1, 1 R2) via right anterior thoracotomy, posterolateral thoracotomy, left thoracoscopy, sternotomy and cervicosternotomy, and/or chemotherapy, mainly cyclophosphamide-doxorubicin-cisplatin (CAP; n = 5), and/or radiotherapy (n = 4). Two patients with TET type C died. All other patients are alive with a median follow-up of 4 years (range: 1.5-20). Review of a total of 93 pediatric cases reported in the literature showed statistically significant associations between less favorable histologic subtypes and male gender (P = 0.012), advanced Masaoka stage (P < 0.001) and quality of resection (P < 0.001) respectively. CONCLUSIONS: A review of the literature and our series identified several risk factors to take into account in the therapeutically decision. Complete resection through a sternotomy is highly recommended. PMID- 25130987 TI - Effect O6-guanine alkylation on DNA flexibility studied by comparative molecular dynamics simulations. AB - Alkylation of guanine at the O6 atom is a highly mutagenic DNA lesion because it alters the coding specificity of the base causing G:C to A:T transversion mutations. Specific DNA repair enzymes, e.g. O(6)-alkylguanin-DNA-Transferases (AGT), recognize and repair such damage after looping out the damaged base to transfer it into the enzyme active site. The exact mechanism how the repair enzyme identifies a damaged site within a large surplus of undamaged DNA is not fully understood. The O(6)-alkylation of guanine may change the deformability of DNA which may facilitate the initial binding of a repair enzyme at the damaged site. In order to characterize the effect of O(6)-methyl-guanine (O(6)-MeG) containing base pairs on the DNA deformability extensive comparative molecular dynamics (MD) simulations on duplex DNA with central G:C, O(6)-MeG:C or O(6) MeG:T base pairs were performed. The simulations indicate significant differences in the helical deformability due to the presence of O(6)-MeG compared to regular undamaged DNA. This includes enhanced base pair opening, shear and stagger motions and alterations in the backbone fine structure caused in part by transient rupture of the base pairing at the damaged site and transient insertion of water molecules. It is likely that the increased opening motions of O(6)-MeG:C or O(6)-MeG:T base pairs play a decisive role for the induced fit recognition or for the looping out of the damaged base by repair enzymes. PMID- 25130988 TI - Paradoxical findings in direct antiglobulin test and classification of agglutinating autoantibodies using eluates and monospecific anti-human globulin sera. AB - BACKGROUND AND OBJECTIVES: Agglutinating autoantibodies are rarely the cause of autoimmune haemolytic anaemia (AIHA) of warm type. These antibodies can be difficult to classify, and serological testing may result in confusion. Here, we describe the occurrence of paradoxical results in direct antiglobulin test (DAT) and a simple technique for the characterization of such antibodies. MATERIALS AND METHODS: Seven patients with AIHA were included in this study. Serological testing was performed using standard techniques. Classification of autoantibodies was performed by preincubation of the eluates from patients' red blood cells (RBCs) with monospecific anti-human globulin sera (mAHG). RESULTS: Strong autoagglutination of patients' RBCs was observed in six of seven cases, with the identification of panagglutinating serum antibodies in three patients. Initially, cold agglutinins with high thermal amplitude were suggested in four patients, and IgM warm autoantibodies were suggested in the remaining three patients. However, inhibition of the eluates revealed autoantibodies of IgA class in two patients, of IgM class in three other cases and of IgG class in two patients. The results of DAT were confusing due to paradoxical effects of mAHG and/or strong autoagglutination. CONCLUSION: Strongly agglutinating autoantibodies can be a source of confusion and can be classified by inhibition experiments using eluates and monospecific antibodies. PMID- 25130989 TI - GMM logistic regression models for longitudinal data with time-dependent covariates and extended classifications. AB - When analyzing longitudinal data, it is essential to account both for the correlation inherent from the repeated measures of the responses as well as the correlation realized on account of the feedback created between the responses at a particular time and the predictors at other times. As such one can analyze these data using generalized estimating equation with the independent working correlation. However, because it is essential to include all the appropriate moment conditions as you solve for the regression coefficients, we explore an alternative approach using a generalized method of moments for estimating the coefficients in such data. We develop an approach that makes use of all the valid moment conditions necessary with each time-dependent and time-independent covariate. This approach does not assume that feedback is always present over time, or if present occur at the same degree. Further, we make use of continuously updating generalized method of moments in obtaining estimates. We fit the generalized method of moments logistic regression model with time dependent covariates using SAS PROC IML and also in R. We used p-values adjusted for multiple correlated tests to determine the appropriate moment conditions for determining the regression coefficients. We examined two datasets for illustrative purposes. We looked at re-hospitalization taken from a Medicare database. We also revisited data regarding the relationship between the body mass index and future morbidity among children in the Philippines. We conducted a simulated study to compare the performances of extended classifications. PMID- 25130990 TI - How accurate is sperm morphology as an indicator of sperm function? AB - Sperm morphology has been consistently correlated with fertilisation success or failure. The clinical relevance of the percentage normal spermatozoa has been a widely discussed topic amongst infertility specialists and scientists. This study aimed to evaluate the role of sperm morphology as an indicator of additional sperm functions among 114 andrology referrals. The sperm functions that were investigated included chromatin packaging quality (CMA3 test (n = 109), zona induced acrosome reaction (ZIAR test; n = 36), hemizona assay (HZI; n = 36) and progressive motility (n = 47). Chromatin packaging quality had a negative and significant (P = 0.0001, r = -0.74) correlation with the percentage normal spermatozoa, while progressive motility had a significant and positive correlation (P = 0.0001, 0.59). Accurate sperm morphology scoring as described by the WHO 2010 manual can therefore be used as an indicator of specific sperm functions. PMID- 25130991 TI - Laterally structured ripple and square phases with one and two dimensional thickness modulations in a model bilayer system. AB - Molecular dynamics simulations of bilayers in a surfactant/co-surfactant/water system with explicit solvent molecules show formation of topologically distinct gel phases depending upon the bilayer composition. At low temperatures, the bilayers transform from the tilted gel phase, Lbeta', to the one dimensional (1D) rippled, Pbeta' phase as the surfactant concentration is increased. More interestingly, we observe a two dimensional (2D) square phase at higher surfactant concentration which, upon heating, transforms to the gel Lbeta' phase. The thickness modulations in the 1D rippled and square phases are asymmetric in two surfactant leaflets and the bilayer thickness varies by a factor of ~2 between maximum and minimum. The 1D ripple consists of a thinner interdigitated region of smaller extent alternating with a thicker non-interdigitated region. The 2D ripple phase is made up of two superimposed square lattices of maximum and minimum thicknesses with molecules of high tilt forming a square lattice translated from the lattice formed with the thickness minima. Using Voronoi diagrams we analyze the intricate interplay between the area-per-head-group, height modulations and chain tilt for the different ripple symmetries. Our simulations indicate that composition plays an important role in controlling the formation of low temperature gel phase symmetries and rippling accommodates the increased area-per-head-group of the surfactant molecules. PMID- 25130993 TI - Role of bisphosphonates in non-metastatic prostate cancer. PMID- 25130994 TI - Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation. AB - BACKGROUND: Ovarian tissue cryopreservation with later reimplantation has been shown to preserve fertility in adult women, but this approach remains unproven and experimental in children and adolescents. We aimed to assess the use of the Edinburgh selection criteria for ovarian tissue cryopreservation in girls and young women with cancer to determine whether we are offering this invasive procedure to the patients who are most at risk of premature ovarian insufficiency. METHODS: Cryopreservation of ovarian tissue has been selectively offered to girls and young women with cancer who met the Edinburgh selection criteria since 1996. Between Jan 1, 1996, and June 30, 2012, 410 female patients younger than 18 years at diagnosis were treated for cancer (including leukaemia and brain tumours) at the Edinburgh Children's Cancer Centre, which serves the whole South East of Scotland region. We determined the ovarian status of these patients from review of clinical records and classified them as having premature ovarian insufficiency or not, or as unable to be determined. Patients younger than 12 years at time of data cutoff (Jan 31, 2013) were excluded from the analysis. FINDINGS: 34 (8%) of the 410 patients met the Edinburgh selection criteria and were offered ovarian tissue cryopreservation before starting cancer treatment. 13 patients declined the procedure and 21 consented, and the procedure was completed successfully in 20 patients. Of the 20 patients who had ovarian tissue successfully cryopreserved, 14 were available for assessment of ovarian function. Of the 13 patients who had declined the procedure, six were available for assessment of ovarian function. Median age at the time of follow-up for the 20 assessable patients was 16.9 years (IQR 15.5-21.8). Of the 14 assessable patients who had successfully undergone ovarian cryopreservation, six had developed premature ovarian insufficiency at a median age of 13.4 years (IQR 12.5 14.6), one of whom also had a natural pregnancy. Of the six assessable patients who had declined the procedure, one had developed premature ovarian insufficiency. Assessment of ovarian function was possible for 141 of the 376 patients who were not offered cryopreservation; one of these patients had developed premature ovarian insufficiency. The cumulative probability of developing premature ovarian insufficiency after treatment was completed was significantly higher for patients who met the criteria for ovarian tissue cryopreservation than for those who did not (15-year probability 35% [95% CI 10 53] vs 1% [0-2]; p<0.0001; hazard ratio 56.8 [95% CI 6.2-521.6] at 10 years). INTERPRETATION: The results of this analysis show that the Edinburgh selection criteria accurately identify the few girls and young women who will develop premature ovarian insufficiency, and validate their use for selection of patients for ovarian tissue cryopreservation. Further follow-up of this cohort of patients is likely to allow refinement of the criteria for this experimental procedure in girls and young women with cancer. FUNDING: UK Medical Research Council. PMID- 25130996 TI - Ovarian tissue cryopreservation in children with cancer. PMID- 25130995 TI - Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial trial. AB - BACKGROUND: We investigated whether 18 months of androgen suppression plus radiotherapy, with or without 18 months of zoledronic acid, is more effective than 6 months of neoadjuvant androgen suppression plus radiotherapy with or without zoledronic acid. METHODS: We did an open-label, randomised, 2 * 2 factorial trial in men with locally advanced prostate cancer (either T2a N0 M0 prostatic adenocarcinomas with prostate-specific antigen [PSA] >=10 MUg/L and a Gleason score of >=7, or T2b-4 N0 M0 tumours regardless of PSA and Gleason score). We randomly allocated patients by computer-generated minimisation- stratified by centre, baseline PSA, tumour stage, Gleason score, and use of a brachytherapy boost--to one of four groups in a 1:1:1:1 ratio. Patients in the control group were treated with neoadjuvant androgen suppression with leuprorelin (22.5 mg every 3 months, intramuscularly) for 6 months (short-term) and radiotherapy alone (designated STAS); this procedure was either followed by another 12 months of androgen suppression with leuprorelin (intermediate-term; ITAS) or accompanied by 18 months of zoledronic acid (4 mg every 3 months for 18 months, intravenously; STAS plus zoledronic acid) or by both (ITAS plus zoledronic acid). The primary endpoint was prostate cancer-specific mortality. This analysis represents the first, preplanned assessment of oncological endpoints, 5 years after treatment. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00193856. FINDINGS: Between Oct 20, 2003, and Aug 15, 2007, 1071 men were randomly assigned to STAS (n=268), STAS plus zoledronic acid (n=268), ITAS (n=268), and ITAS plus zoledronic acid (n=267). Median follow-up was 7.4 years (IQR 6.5-8.4). Cumulative incidences of prostate cancer-specific mortality were 4.1% (95% CI 2.2-7.0) in the STAS group, 7.8% (4.9-11.5) in the STAS plus zoledronic acid group, 7.4% (4.6 11.0) in the ITAS group, and 4.3% (2.3-7.3) in the ITAS plus zoledronic acid group. Cumulative incidence of all-cause mortality was 17.0% (13.0-22.1), 18.9% (14.6-24.2), 19.4% (15.0-24.7), and 13.9% (10.3-18.8), respectively. Neither prostate cancer-specific mortality nor all-cause mortality differed between control and experimental groups. Cumulative incidence of PSA progression was 34.2% (28.6-39.9) in the STAS group, 39.6% (33.6-45.5) in the STAS plus zoledronic acid group, 29.2% (23.8-34.8) in the ITAS group, and 26.0% (20.8-31.4) in the ITAS plus zoledronic acid group. Compared with STAS, no difference was noted in PSA progression with ITAS or STAS plus zoledronic acid; however, ITAS plus zoledronic acid reduced PSA progression (sub-hazard ratio [SHR] 0.71, 95% CI 0.53-0.95; p=0.021). Cumulative incidence of local progression was 4.1% (2.2-7.0) in the STAS group, 6.1% (3.7-9.5) in the STAS plus zoledronic acid group, 1.5% (0.5-3.7) in the ITAS group, and 3.4% (1.7-6.1) in the ITAS plus zoledronic acid group; no differences were noted between groups. Cumulative incidences of bone progression were 7.5% (4.8-11.1), 14.6% (10.6-19.2), 8.4% (5.5-12.2), and 7.6% (4.8-11.2), respectively. Compared with STAS, STAS plus zoledronic acid increased the risk of bone progression (SHR 1.90, 95% CI 1.14-3.17; p=0.012), but no differences were noted with the other two groups. Cumulative incidence of distant progression was 14.7% (10.7-19.2) in the STAS group, 17.3% (13.0-22.1) in the STAS plus zoledronic acid group, 14.2% (10.3-18.7) in the ITAS group, and 11.1% (7.6-15.2) in the ITAS plus zoledronic acid group; no differences were recorded between groups. Cumulative incidence of secondary therapeutic intervention was 25.6% (20.5-30.9), 28.9% (23.5-34.5), 20.7% (16.1-25.9), and 15.3% (11.3-20.0), respectively. Compared with STAS, ITAS plus zoledronic acid reduced the need for secondary therapeutic intervention (SHR 0.67, 95% CI 0.48-0.95; p=0.024); no differences were noted with the other two groups. An interaction between trial factors was recorded for Gleason score; therefore, we did pairwise comparisons between all groups. Post-hoc analyses suggested that the reductions in PSA progression and decreased need for secondary therapeutic intervention with ITAS plus zoledronic acid were restricted to tumours with a Gleason score of 8-10, and that ITAS was better than STAS in tumours with a Gleason score of 7 or lower. Long-term morbidity and quality-of-life scores were not affected adversely by 18 months of androgen suppression or zoledronic acid. INTERPRETATION: Compared with STAS, ITAS plus zoledronic acid was more effective for treatment of prostate cancers with a Gleason score of 8-10, and ITAS alone was effective for tumours with a Gleason score of 7 or lower. Nevertheless, these findings are based on secondary endpoint data and post-hoc analyses and must be regarded cautiously. Long- term follow-up is necessary, as is external validation of the interaction between zoledronic acid and Gleason score. STAS plus zoledronic acid can be ruled out as a potential therapeutic option. FUNDING: National Health and Medical Research Council of Australia, Novartis Pharmaceuticals Australia, Abbott Pharmaceuticals Australia, New Zealand Health Research Council, New Zealand Cancer Society, University of Newcastle (Australia), Calvary Health Care (Calvary Mater Newcastle Radiation Oncology Fund), Hunter Medical Research Institute, Maitland Cancer Appeal, Cancer Standards Institute New Zealand. PMID- 25130997 TI - Dual targeting of HER2 with lapatinib and trastuzumab. PMID- 25130999 TI - Is elevated beta-hexosaminidase activity a potential biomarker for Parkinson's disease? PMID- 25130998 TI - Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. AB - BACKGROUND: Findings from the randomised phase 3 NeoALTTO trial in women with HER2-positive early breast cancer showed that the combination of lapatinib and trastuzumab significantly improved rates of pathological complete response compared with either drug alone. Here, we report data for the prespecified secondary endpoints of event-free and overall survival, and assess the association between these outcomes and pathological complete response. METHODS: We enrolled women with HER2-positive early breast cancer and randomly assigned them to receive oral lapatinib (1500 mg), intravenous trastuzumab (4 mg/kg loading dose followed by 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab (same dose as for single agent) in combination for 6 weeks, followed by an additional 12 weeks of the assigned anti-HER2 therapy in combination with weekly paclitaxel (80 mg/m(2)). Definitive surgery was done 4 weeks after the last dose of paclitaxel. After surgery, women received three cycles of FEC (fluorouracil 500 mg/m(2) plus epirubicin 100 mg/m(2) plus cyclophosphamide 500 mg/m(2)) given intravenously every 3 weeks, followed by 34 weeks of the same assigned neoadjuvant anti-HER2 therapy. The primary endpoint was pathological complete response. Secondary endpoints included event-free and overall survival (intention to-treat analysis), and the association between pathological complete response and event-free or overall survival (analysed by landmark analysis at 30 weeks after randomisation). Follow-up is ongoing, and the trial is registered with ClinicalTrials.gov, number NCT00553358. FINDINGS: 455 patients were enrolled: 154 (34%) were assigned to the lapatinib group, 149 (33%) to the trastuzumab group, and 152 (33%) to the lapatinib plus trastuzumab group. At an event follow-up of 3.77 years (IQR 3.50-4.22), 3-year event-free survival was 78% (95% CI 70-84) in the lapatinib group, 76% (68-82) in the trastuzumab group, and 84% (77-89) in the combination group. Event-free survival did not differ between the lapatinib and trastuzumab groups (HR 1.06, 95% CI 0.66-1.69, p=0.81), nor between the combination and trastuzumab groups (0.78, 0.47-1.28, p=0.33). Median survival follow-up was 3.84 years (IQR 3.60-4.24), and 3-year overall survival was 93% (95% CI 87-96) for lapatinib, 90% (84-94) for trastuzumab, and 95% (90-98) for combination therapy. Overall survival did not significantly differ between the lapatinib and trastuzumab groups (HR 0.86, 95% CI 0.45-1.63, p=0.65), nor between the combination and trastuzumab groups (0.62, 0.30-1.25, p=0.19). Landmark analyses showed that 3-year event-free survival was significantly improved for women who achieved pathological complete response compared with those who did not (HR 0.38, 95% CI 0.22-0.63, p=0.0003), as was 3-year overall survival (0.35, 0.15 0.70, p=0.005). Adverse events occurred in 149 (99%) patients receiving lapatinib, 142 (96%) patients receiving trastuzumab, and 147 (99%) patients receiving combination therapy. The most common adverse events were diarrhoea, rash or erythema, hepatic adverse events, and neutropenia (not related to FEC administration), and were consistent with known safety profiles of lapatinib and trastuzumab. Three primary and eight secondary cardiac events occurred, with no significant difference in incidence between treatment groups for primary or any cardiac events. INTERPRETATION: Although event-free survival or overall survival did not differ between treatment groups, findings from our study confirm that patients who achieve pathological complete response after neoadjuvant anti-HER2 therapy have longer event-free and overall survival than do patients without pathological complete response. FUNDING: GlaxoSmithKline. PMID- 25131000 TI - The efficacy of steroids for edema and ecchymosis after rhinoplasty: a meta analysis. AB - OBJECTIVES: Postoperative periorbital edema and ecchymosis following rhinoplasty can result in dissatisfaction for both the surgeon and the patient. The goal of this study was to perform a systematic review of the literature on the efficacy of steroids on edema and ecchymosis during rhinoplasty. DATA SOURCES: MEDLINE, SCOPUS, and Cochrane database. REVIEW METHODS: Two authors independently searched the databases from their inception of article collection to February 2014. Studies comparing perioperative steroid administration (steroid group) with no treatment (control group) where the outcomes of interest were edema and ecchymosis on postoperative days were included in the analysis. Overall, a total of nine trials met the inclusion criteria of this study, with a total sample size of 312 patients. RESULTS: The lower and upper eyelid edema during the 7 days postoperatively was statistically decreased in the steroid group versus control group. The lower and upper eyelid ecchymosis in the steroid group was significantly decreased in comparison to the control group for the first 4 days follow surgery. Regarding the outcome comparison between single-dose and multiple dose administration of steroids, the multiple-dose administration decreased edema and ecchymosis significantly compared to single-dose administration after the fourth day. CONCLUSIONS: Perioperative administration of steroid during rhinoplasty could reduce the level of edema and eyelid ecchymosis. Multiple-dose administration of steroids has more advantages in terms of the outcomes of late postoperative edema and ecchymosis compared to a single-dose regimen. PMID- 25131001 TI - The antimicrobial activity of fruits from some cultivar varieties of Rubus idaeus and Rubus occidentalis. AB - Raspberries, derived from different cultivar varieties, are a popular ingredient of everyday diet, and their biological activity is a point of interest for researchers. The ethanol-water extracts from four varieties of red (Rubus idaeus'Ljulin', 'Veten', 'Poranna Rosa') and black (Rubus occidentalis'Litacz') raspberries were evaluated in the range of their antimicrobial properties as well as phenolic content - sanguiin H-6, free ellagic acid and anthocyanins. The antimicrobial assay was performed with the use of fifteen strains of bacteria, both Gram-negative and Gram-positive. The antimicrobial activity of the extracts varied and depended on the analysed strain of bacteria and cultivar variety, with the exception of Helicobacter pylori, towards which the extracts displayed the same growth inhibiting activity. Two human pathogens Corynebacterium diphtheriae and Moraxella catarrhalis proved to be the most sensitive to raspberry extracts. Contrary to the extracts, sanguiin H-6 and ellagic acid were only active against eight and nine bacterial strains, respectively. The determined MIC and MBC values of both compounds were several times lower than the tested extracts. The highest sensitivity of Corynebacterium diphtheriae to extracts from both black and red raspberries may be due to its sensitivity to sanguiin H-6 and ellagic acid. PMID- 25131003 TI - Failure of replicating the association between hippocampal volume and 3 single nucleotide polymorphisms identified from the European genome-wide association study in Asian populations. AB - Hippocampal volume is a key brain structure for learning ability and memory process, and hippocampal atrophy is a recognized biological marker of Alzheimer's disease. However, the genetic bases of hippocampal volume are still unclear although it is a heritable trait. Genome-wide association studies (GWASs) on hippocampal volume have implicated several significantly associated genetic variants in Europeans. Here, to test the contributions of these GWASs identified genetic variants to hippocampal volume in different ethnic populations, we screened the GWAS-identified candidate single-nucleotide polymorphisms in 3 independent healthy Asian brain imaging samples (a total of 990 subjects). The results showed that none of these single-nucleotide polymorphisms were associated with hippocampal volume in either individual or combined Asian samples. The replication results suggested a complexity of genetic architecture for hippocampal volume and potential genetic heterogeneity between different ethnic populations. PMID- 25131002 TI - Age-associated evolution of plasmatic amyloid in mouse lemur primates: relationship with intracellular amyloid deposition. AB - Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Amyloid-beta peptide (Abeta) deposition in the brain is one of its hallmarks, and the measure of plasma Abeta is considered to be a biomarker for anti-amyloid drug efficacy in animal models of AD. However, age-associated plasmatic Abeta modulation in animal models is practically never addressed in the literature. Mouse lemur primates are used as a model of normal and AD-like cerebral aging. Here, we studied the effect of age on plasmatic Abeta in 58 mouse lemurs aged from 1 to 10 years. A subset of animals presented high plasmatic Abeta, and the proportion of animals with high plasmatic Abeta was higher in aged animals as compared with young ones. Histologic evaluation of the brain of some of these animals was carried out to assess extracellular and intracellular amyloid load. In aged lemurs, plasmatic Abeta was negatively correlated with the density of neurons accumulating deposits of Abeta. PMID- 25131005 TI - Response to Dr. Sertoglu and colleagues. PMID- 25131004 TI - Single neuropsychological test scores associated with rate of cognitive decline in early Alzheimer disease. AB - Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression. PMID- 25131007 TI - Organ transplants and education: experience of the Universidade Federal de Ciencias da Saude de Porto Alegre with subjects. AB - INTRODUCTION: Today there is an insufficient number of donated organs in Brazil. This is particularly due to the general population's and health care professionals' lack of information. Therefore, with this project we intend to consolidate knowledge on organ donation to teach health care students of different areas so they are able to propagate such knowledge. MATERIALS AND METHODS: In 2006, at Universidade Federal de Ciencias da Saude de Porto Alegre, an "Organ donation and transplants" subject was created, with the aim to educate health care students. In the next years, it was split in two subjects, named "Introduction to transplants" and "Donation and transplants." By enrolling, students get theoretical classes and practical experience in out- and inpatient facilities and in surgical environments at the Santa Casa Hospital Complex. Furthermore, they can participate in campaigns at parks, stadiums, and health care fairs that take place at several schools in Porto Alegre. To finish the subjects, students present a conclusion report. RESULTS: Seven years after implementation of the subject, and with more than 400 students enrolled, several accomplishments can be highlighted. For example, the creation of the Organ Transplantation League, the implementation of a day to spread conception of the donation-transplant process (with the elaboration of a Web page on the subject), and the release of a book on the subject written by students and professors. DISCUSSION AND CONCLUSION: Health care professionals' education is a central point in donation and transplant process. This is because they become, inevitably, educators, and this brings a long-term consequence, consisting of enhanced logistics skills on brain-death diagnosis and further transfer of information to the population (hopefully reducing denial by families at the time of the donation). We conclude that this is a project to be followed by other medical schools so that, effectively, the number of donors increases and, consequently, the transplantation of organs and tissues as well. PMID- 25131008 TI - Reasons for family refusal of ocular tissue donation. AB - INTRODUCTION: Corneal donations do not fill the transplant demand. The waiting list had 5512 individuals in Brazil and 143 in Rio Grande do Sul in December 2012. The aim of this study was to identify the reasons for family refusal of ocular tissues donation. METHODS: This retrospective study analyzed interview records for ocular tissue procurement performed in a general, public university hospital located in Southern Brazil between January 2008 and December 2012. It identified the reasons of family refusal for ocular tissue donation. RESULTS: A total of 1010 interviews for ocular tissues procurement were performed. From these, 513 (50.79%) refused donation with the following reasons: 60 (11.69%) family members were unaware of the desire of the potential donor, 153 (29.82%) of potential donors spoke against donation in life, 113 (22.02%) family members were undecided about the donation, 156 (30.40%) family members were against donation, 3 (0.58%) family members were unhappy with the service, 11 (2.14%) family members were afraid of body release delay, 6 (1.16%) families expressed religious convictions against donation, and 11 (2.14%) family members wanted to keep the body intact. CONCLUSION: There are many reasons for ocular tissues donation refusal, and the knowledge provides better strategies for family interviews. In this study, most of the reasons, around 90%, can be related to lack of information or communication about the subject. Greater awareness of the population about the subject can be a good way to increase ocular tissue procurement indexes. PMID- 25131009 TI - Family informed consent to organ donation--who performs better: organ procurement organizations, in-hospital coordinators, or intensive care unit professionals? AB - Successful organ donation in countries adopting informed consent legislation depends on adequate interviewing of potential donors' families. As the number of both referral and effective donors in Brazil increases, health care managers argue whether educational efforts should be directed toward training in-hospital coordinators (IHC)--based on the "Spanish model"--or on the creation of extra hospital-based professionals (Organ Procurement Organizations [OPOs], the "American model"). Meanwhile, many potential donor families are still approached by intensive care unit (ICU) professionals not trained in donation interviews. The aim of our study was to compare performances in obtaining informed consent from potential donors' families, according to the type of health care professional conducting the interviews: OPO, IHC, or ICU staff. In this retrospective 2-year study performed in Rio de Janeiro, Brazil, we observed an increase in referrals (285 to 411) and consent rates (48.1% to 55.7%). Each year, OPO professionals conducted most family interviews (58.6% and 60.4%, respectively) and obtained better consent rates (63.5% and 64.5%, respectively), when compared to IHC (41.8% and 53.7%, respectively) or untrained ICU professionals (22.1% and 13.4%, respectively). Our results show that adequate professional training is necessary for obtaining family consent for organ donation. Both established international policies for organ procurement and donation, namely the "Spanish model" with its IHCs or the "American model" of extra-hospital OPOs, may equally achieve this task. However, family interviews performed by untrained ICU professionals result in low donation rates and should be discouraged. PMID- 25131010 TI - The family interview in the process of donating organs and tissues for transplantation: perceptions of potential donors' relatives. AB - BACKGROUND: The family interview is a complex phase of the organ donation process because it involves aspects of the interviewer, the interviewee, the interview location, and ethical and legal issues. However, there are few publications on this phase of the donation process. This study aimed to reveal the meaning assigned to the interview phase, in the process of donating organs and tissues for transplantation, by the families of potential donors. METHODS: We performed a qualitative study of the phenomenologic aspect, within the modality "structure situated phenomena." The study included the participation of 10 families. RESULTS: After analyzing the interviews, the meaning of the interview was unveiled by the family members. CONCLUSIONS: The statements revealed that the family interview is considered to be an important step for warnings, clarifications, and encouraging families to think about the possibility of donating to save and/or improve the quality of life of people in need for a transplant, and that studies contribute to the technical and scientific qualification of the interviewer as well as stimulate discussion among health professionals to improve the interviewing process. PMID- 25131011 TI - Genetic expression profile of human liver grafts in ischemia-reperfusion injury: comparison of familial amyloidotic polyneuropathy and deceased-donor liver grafts. AB - This study aimed to compare the histologic and molecular gene expression at several surgical times (beginning of harvesting, T0; end of cold ischemia period, T1; and after reperfusion, T2) to characterize the ischemia-reperfusion injury (IRI) in deceased-donor liver grafts harvested from patients with familial amyloidotic polyneuropathy (FAP). For this purpose, 54 patients undergoing liver transplantation were studied and divided into 3 groups: deceased donor to cirrhotic recipient (group 1; n = 27), deceased donor to FAP recipient (group 2; n = 15), and FAP donor to cirrhotic recipient (group 3; n = 12). The main comparison was performed between a histologic score (Suzuki score, adding steatosis and neutrophil infiltration), and molecular gene expression of the following genes: interleukin (IL) 1beta, IL-6, E-selectin, Fas-ligand, granzyme B, heme oxygenase 1 (HO1), and nitric oxide synthetase (iNOS2A). We observed less neutrophil infiltration levels in group 3 in sample T0 (P = .0082), which was associated with gene expression of HO1 in the biopsies at T2 (P = .022). In group 3, the molecular expression of genes related to attenuated proinflammatory reaction during IRI, iNOS2A at T0 and HO1 at T2, was detected. We conclude that FAP liver grafts express differently the genes associated with an attenuated proinflammatory reaction, presenting less neutrophil infiltration at harvesting. These findings add more knowledge about the better short-term outcomes in patients receiving this type of liver graft. PMID- 25131012 TI - Evaluation of the reasons for nonacceptance of kidneys retrieved or offered in Rio Grande do Sul and Pais Vasco. AB - In Rio Grande do Sul (RS), as in Pais Vasco (PV), some kidneys are retrieved or offered and not accepted for transplantation. This study aimed to evaluate the profile of the available kidneys and the reasons for them not being accepted in the 2 regions, and to compare the characteristics of the organs and reasons for refusal. All of the kidneys retrieved or offered in RS in December 2012 and in PV from September to December 2012 were evaluated. Data were collected from each local donation registry. There were 61 kidneys available in RS and 61 in PV in the study period. Of these, 16 kidneys (26%) in RS and 27 (44%) in PV were not implanted. The age of the donors was higher in PV (59 years) than in RS (45 years; P = .000), as was the age of the donors of accepted kidneys (62 and 41 years old, respectively; P = .000). The proportion of donors considered to be "extended criteria" was higher in PV (78%) than in RS (47%; P = .001), and the refusal rate of the kidneys from these donors was the same in the 2 regions. The reasons for not using the kidneys in RS and in PV were similar and absolute. It is concluded that there is no organ waste in the 2 regions, but that the offer of kidneys can be expanded in RS by considering elderly donors for evaluation, even if this means a higher number of refused organs. PMID- 25130992 TI - Linking temporal changes in bacterial community structures with the detection and phylogenetic analysis of neutral metalloprotease genes in the sediments of a hypereutrophic lake. AB - We investigated spatial and temporal variations in bacterial community structures as well as the presence of three functional proteolytic enzyme genes in the sediments of a hypereutrophic freshwater lake in order to acquire an insight into dynamic links between bacterial community structures and proteolytic functions. Bacterial communities determined from 16S rRNA gene clone libraries markedly changed bimonthly, rather than vertically in the sediment cores. The phylum Firmicutes dominated in the 4-6 cm deep sediment layer sample after August in 2007, and this correlated with increases in interstitial ammonium concentrations (p < 0.01). The Firmicutes clones were mostly composed of the genus Bacillus. npr genes encoding neutral metalloprotease, an extracellular protease gene, were detected after the phylum Firmicutes became dominant. The deduced Npr protein sequences from the retrieved npr genes also showed that most of the Npr sequences used in this study were closely related to those of the genus Bacillus, with similarities ranging from 61% to 100%. Synchronous temporal occurrences of the 16S rRNA gene and Npr sequences, both from the genus Bacillus, were positively associated with increases in interstitial ammonium concentrations, which may imply that proteolysis by Npr from the genus Bacillus may contribute to the marked increases observed in ammonium concentrations in the sediments. Our results suggest that sedimentary bacteria may play an important role in the biogeochemical nitrogen cycle of freshwater lakes. PMID- 25131013 TI - Ten years' evaluation of potential pancreas donors in Sao Paulo, Brazil. AB - BACKGROUND: Pancreas transplantation is a treatment for advanced type 1 diabetes and offers significant improvement in quality of life. Recent advances in surgical techniques and immunosuppression regimes lead to good outcomes. However, despite significant higher rates of multiorgan donors in Brazil, pancreas transplantation seems to have remained stable. This study aimed to investigate the acceptance rate of potential pancreas donors in the past 10 years in Sao Paulo State. METHODS: We retrospectively evaluated potential pancreas donors characteristics and its acceptance rate in Sao Paulo State in the past 10 years. We divided this period into 2 eras: 1st era from January 2003 to January 2008; and 2nd era from January 2008 to January 2013. Data were obtained from Sao Paulo's government official website. RESULTS: During the whole period, 5,005 deceased donors of all ages were available for pancreas transplantation. According to eras, we had 1,588 donors in the 1st and 3,417 in the 2nd era. In the 2nd era, donors >49 years old were significantly more common (P < .001). Blood test abnormalities, donor comorbidities, and high dosage of vasopressors also were significantly higher in the 2nd era. Rate of graft acceptance had a significant decrease in the 2nd era, from 46.4% to 25% (P < .05). CONCLUSIONS: Despite greater organ availability, pancreas transplantations performed in Sao Paulo State remained stable. Rate of graft acceptance is dramatically lower in more recent years. PMID- 25131014 TI - Profile of organ donors in Ceara, northeastern Brazil, from 1998 to 2012. AB - The use of cadaver donors for transplantation is often the only alternative in the treatment of patients with organ failure. The purpose of this study was to draw a comprehensive profile of solid organ donors in Ceara, northeastern Brazil, from 1998 to 2012. The study was retrospective and based on secondary data regarding sex, age, blood typing, and cause of brain death obtained from the solid organ donor database of the Ceara Transplantation Center covering the period November 1998 to December 2012. During the study period, 976 donors (69% male) were used. Donors were distributed in 4 age groups as follows: 12.9% <18 years, 50.9% 18-40 years, 28.5% 41-60 years, and 7.7% >60 years. The average age was 35 +/- 16 years. On the average, female donors were older than male donors (38.4 +/- 17 y vs 33.5 +/- 16 y; P < .0001). Men were predominant in the age groups 18-40 y (75.3%; P < .0001) and 41-60 y (59.4%; P < .0001). The main causes of brain death were traumatic brain injury (TBI) (56.7%) and stroke (33.1%). The former was more common in men (P < .0001), the latter in women (P < .0001). TBI was caused by traffic accidents (51.4%), of which 50.7% were motorcycle accidents, and urban violence (22.6%), of which 71.2% were associated with firearms. The number of donations increased in the study period (11.2 donors per million population in 1998-2002 to 68.1 in 2008-2012). In Ceara, solid organ donation is on the rise. The predominant donor profile was young men aged 18-40 years with brain death due to TBI caused by traffic accidents and urban violence. PMID- 25131015 TI - Waiting for a kidney transplant: association with anxiety and stress. AB - BACKGROUND: The pretransplantation period is characterized by many stressful events that can result in symptoms of anxiety and stress and ultimately can have a negative impact on graft outcome. Our objective was to evaluate the association between symptoms of anxiety and stress in patients awaiting kidney transplantation. METHODS: This was a transversal study describing 50 randomly selected patients undergoing hemodialysis and waitlisted for kidney transplantation. We collected social and demographic data, and adopted the Beck Anxiety Inventory and the Lipp Stress Symptoms for Adults Inventory to respectively evaluate anxiety and stress. RESULTS: The mean age was 50.2 +/- 11.7 years, 54% of patients were female, time on dialysis was 6.5 +/- 4.5 years, and transplant waitlist time was 5.9 +/- 4.4 years. Forty-six percent of patients were married or had a stable relationship, 50% were illiterate or had only finished primary school, and 64% were pensioners. Stress was documented in 60% of patients, of which 30% had severe stress, whereas 56% of patients showed symptoms of anxiety. The presence of stress was associated with longer waitlist time (P = .006) and longer time on dialysis (P = .052). Less severe stress was associated with higher education level (P = .031), whereas patients in more advanced phases of stress showed higher levels of anxiety. After a multivariate analysis, stress was 3.6 times (CI 1.34 to 9.89) more frequent among individuals with anxiety. CONCLUSIONS: Stress and anxiety were prevalent in patients on a waitlist and were associated with social and chronic kidney disease-related patterns. This observation can stimulate the adoption of strategies for the prevention of stress and anxiety, avoiding posttransplantation complications, such as nonadherence to treatment. PMID- 25131016 TI - Historical cohort with diabetes mellitus after kidney transplantation and associated factors of its development in adult patients of a transplantation reference center in the State of Ceara, Brazil. AB - Post-transplantation diabetes mellitus (PTDM) is an important complication related to kidney transplantation (KT), and its occurrence is associated with increased morbidity and mortality. Nevertheless, KT is considered to be the most effective treatment option that offers better quality of life for patients with end-stage kidney disease. This study aimed to describe the occurrence of PTDM and the risk factors associated with its development in kidney transplant patients of a transplantation reference center in the State of Ceara (Brazil). This historical cohort study, based on medical records data, included adult patients undergoing KT from January 2006 to December 2010 in a public tertiary hospital. Multivariate analysis was performed with the use of a logistic regression model, with PTDM presence as dependent variable and the possible risk factors under study as independent variables. Throughout the evaluated period, 430 KTs were performed; 92 patients were excluded. Diabetes mellitus was already present in 9.2% of patients before KT. Hyperglycemia during the 1st month after transplantation occurred in 34.5% of recipients, and the occurrence of PTDM to the end of study was 19.9%. Factors associated with PTDM development were: fasting plasma glucose 1 month after KT (P < .001; odds ratio [OR] 1.05), deceased-donor KT (P = .015; OR 3.53), impaired fasting glucose before transplantation (P = .014; OR 4.10), and acute rejection occurrence (P = .003; OR 6.43). High PTDM occurrence was found, in accordance with the literature. Identification of factors associated with PTDM development, as well as its early diagnosis, could result in long-term improvement in patient and graft survivals. PMID- 25131017 TI - Kidney transplantation across a positive crossmatch: a single-center experience. AB - BACKGROUND: Kidney transplantation is the treatment of choice for end-stage renal disease, with improved mortality and quality of life compared with dialysis. Desensitization protocols have allowed kidney transplantation of highly sensitized patients, who have a lower probability to receive a matching kidney from a deceased or living donor. The aim of this work was to analyze the post transplantation period of highly HLA-sensitized patients with positive flow cytometry crossmatch against donor cells. METHODS: Following an observational, retrospective design, we investigated 16 highly sensitized patients who underwent kidney or kidney-pancreas transplantation, assessing the impact of desensitization protocols and investigating treatment-related complications, graft function, antibody-mediated rejection (AMR) rate, and graft and patient survivals. RESULTS: We studied 16 patients with positive flow cytometry crossmatch, who were divided into 2 groups based on whether they were submitted to a desensitization protocol or not. Patients who were desensitized underwent transplantation in later years, had higher immunologic risk (panel reactive antibody peak 62% vs 33%; P = .038), higher percentage of 2nd kidney transplant (75% vs 25%; P = .066), and higher percentage of donor-specific anti-HLA antibodies identified (P = .028). A majority of patients were desensitized with high-dose intravenous immunoglobulin and plasmapheresis, and 5 patients received rituximab. Acute AMR rate was of 38%, and rituximab was associated with fewer episodes of AMR. Only 1 patient had graft failure, due to chronic humoral rejection, and the remaining maintained good graft function (mean serum creatinine value of 1.33 mg/dL). No patient died and few complications related to immunossupression were observed. CONCLUSIONS: Desensitization protocols were safe and allowed kidney transplantation in highly sensitized patients that probably would never undergo transplantation and gave the opportunity of living-donor transplant to patients with anti-HLA antibodies against the donor. PMID- 25131018 TI - C4d deposits in borderline rejection: an early marker for chronic renal dysfunction? AB - The impact of borderline rejection in renal graft remains controversial. The aim of this study was to analyze the presence of C4d deposits in peritubular capillaries and macrophage infiltration in renal biopsies with diagnosis of borderline rejection ant its effect on graft function. Thirty-one renal transplant recipients with a diagnosis of borderline rejection were included. Initial and sequential biopsies were analyzed for morphology, C4d, and macrophage staining and compared with clinical data. Initial biopsies showed 12 samples to be C4d positive, associated with a higher incidence of delayed graft function, earlier post-transplantation time, higher acute tubular necrosis score, capillaritis, and glomerular macrophage infiltration, and a lower level of tubulitis, interstitial fibrosis, and tubular atrophy compared with the C4d negative samples. In sequential biopsies, 5 patients from the negative group turned C4d positive. Patients with >=1 positive C4d biopsy (n = 17) showed lower renal graft function at 6 months (1.8 +/- 0.8 vs 1.4 +/- 0.5 mg/dL; P < .01), 1 year (2.1 +/- 1 vs 1.5 +/- 0.5 mg/dL; P < .01), and 2 years (2.3 +/- 1.3 vs 1.5 +/- 0.7 mg/dL; P < .05) of follow-up. The expression of C4d in peritubular capillaries of renal biopsies classified as borderline rejection was associated with a worse prognosis for the renal allograft. PMID- 25131020 TI - Renal transplantation in human immunodeficiency virus-positive patients: a report of four cases. AB - INTRODUCTION: Renal transplantation (RT) in patients infected with human immunodeficiency virus (HIV) has significantly improved under the advent of combined antiretroviral therapy (cART). The authors describe their experience in RT in patients with HIV from September 2010 to June 2013. CASES REPORT: Four patients underwent transplantation (3 with HIV-1 and 1 with HIV-2), three patients were male, and one was black. None were coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV). Etiology of kidney disease was HIV associated nephropathy (2 patients), immunoglobulin (Ig)A nephropathy, and unknown. Average age at RT was 51 (range, 41-63) years. No patient was of high immunologic risk. Immunosuppression consisted of basiliximab for induction and prednisolone, tacrolimus (TAC), and mycophenolate mofetil for maintenance. TAC levels varied considerably in the early days (8.5-46 ng/mL), requiring major adjustments in TAC dose. Only the HIV-2 patient had delayed graft function. The follow-up of patients with HIV-1 was 37, 19, and 16 months, and 3 months for the HIV-2 patient. CD4+ T cells decreased in the early days after transplantation with subsequent improvement, along with persistent virological suppression. In the HIV-1 group there were no major infectious, cardiovascular, or neoplastic complications. Nevertheless, the HIV-2 patient died 3 months after RT due to H1N1 pneumonia complicated by pulmonary aspergillosis. Average estimated (CKD- EPI) glomerular filtration rate (eGFR) at 6 months was 85.6 mL/min/1.73 m(2). CONCLUSION: Besides the difficulty in adjusting calcineurin inhibitors levels due to its interaction with antiretroviral therapy, namely with protease inhibitors, no patient had acute rejection. Furthermore, all patients presented an excellent control of viro-immunologic parameters. At the last follow-up neither cardiovascular events nor neoplastic complications were observed. Our results highlight the favorable outcome of RT in HIV-1-infected patients. The HIV-2 patient died due to severe infection, and the clinical management and potential benefit of RT in HIV-2-infected patients needs further study. PMID- 25131021 TI - Predictive factors of graft-censored failure in pediatric kidney transplantation. AB - Kidney transplantation in children has shown steady improvement in graft survival outcome over the last decades. Using data obtained from the transplantation registry of our center between 1984 and 2012, we assessed the independent determinants of graft failure using the Cox proportional hazards regression. Altogether, 128 recipients younger than 18 years of age at the time of kidney transplantation and who had >3 months graft survival were studied. During 9.95 years of medium follow-up, 27 censored graft failures occurred. Censored graft survival rates at 5, 10, 15, and 20 years post-transplantation were 93%, 82%, 70%, and 63%, respectively. Studied factors included recipient and donor age, recipient gender, dialysis vintage, donor/recipient cytomegalovirus (CMV) serology, panel-reactive antibody percentage, human leukocyte antigen mismatching, previous transplantation number, donor type (deceased vs living donation), cold ischemia time, induction therapy with antithymocyte globulin, occurrence of acute tubular necrosis, and development of acute rejection. Using univariate analysis, the significant predictors for graft-censored failure were adult donor (P < .001), recipient age (P = .035), human leukocyte antigen mismatching (P = .025), antithymocyte globulin induction (P = .03), and development of acute rejection (P < .001). Two factors independently predicted graft-censored failure in multivariate analysis. The odds ratios for graft failure in patients with acute rejection and in children who received an organ of an adult were 3.744 and 4.962, respectively. Pediatric recipients should receive the first priority for allografts from pediatric donors and acute rejection should be meticulously prevented. PMID- 25131019 TI - Physical activity in daily life assessed by an accelerometer in kidney transplant recipients and hemodialysis patients. AB - BACKGROUND: Sedentary lifestyle is a problem among hemodialysis (HD) patients, potentially attenuated after kidney transplantation. However, the effect of kidney transplantation on physical activity has not been thoroughly investigated. OBJECTIVE: This study sought to evaluate the physical activity in daily life in kidney transplant recipients (KTRs) compared with HD patients and to explore its relationship with clinical variables. METHODS: A cross-sectional study enrolled KTRs who received transplants at least 6 months before the study (N = 23; 48.3 +/ 10.3 years) and patients undergoing HD for at least 6 months (N = 20; 47.3 +/- 12.6 years). Time spent in different activities (walking, standing, sitting, and lying down) and number of steps taken, measured by a multiaxial accelerometer used for 12 h/d on 2 consecutive days for KTRs and on 4 consecutive days for HD patients, were evaluated. RESULTS: KTRs engaged in more active time per day (sum of walking and standing time) than HD patients (311 +/- 87 vs 196 +/- 54 min/d; P = .001), with longer walking (106 +/- 53 vs 70 +/- 27 min/d; P = .008) and standing time (205 +/- 55 vs 126 +/- 42 min/d; P < .001). Sixty-five percent of KTRs were classified as active (>7500 steps/d) compared with only 20% of the HD group (P < .05). The multivariate analysis showed that time posttransplantation was significantly associated with walking time and active time. CONCLUSIONS: By using an accelerometer, a precise method, this study showed that KTRs are significantly more active in daily life than HD patients, and that daily physical activity increases with time since transplantation. PMID- 25131022 TI - Incidence, risk factors, and outcomes of delayed graft function in deceased donor kidney transplantation in a Brazilian center. AB - BACKGROUND: A high incidence of delayed graft function (DGF) after deceased donor kidney transplantation occurs in Brazil. The reasons for such have not been adequately studied. METHODS: We performed a retrospective cohort study of 346 kidney transplant recipients from deceased donors. DGF risk factors related to the recipient, donor, and transplantation surgery were analyzed and correlated with graft outcomes. A logistic regression analysis was used to identify independent risk factors and patient and graft survival were assessed using Kaplan-Meier curves. RESULTS: The incidence of DGF was 70.8% (245 cases). Our final model of multivariate analysis showed that DGF is associated (P < .05) with donor final serum creatinine (relative risk [RR], 1.84; 95% confidence interval [CI], 1.26-2.70), donor age (RR, 1.02 [1.0-1.033]), receiving a kidney from national offer (RR, 2.44 [1.06-5.59]), and need for antibody induction (RR, 2.87 [1.33-6.18]). Outcomes that were associated with DGF were longer length of hospital stay (32.5 +/- 20.5 vs 18.8 +/- 16.3 days; P = .01), higher incidence of acute rejection (37.8 vs 12.9%; P < .01), worse graft survival at 1 year (83.5% vs 93.9%; P < .01), and higher levels of serum creatinine at 3, 6, and 12 months (P < .05). There was no difference in patient survival and the occurrence of acute rejection did not influence the survival of patients or grafts. CONCLUSION: DGF was associated with higher donor final serum creatinine, donor age, receiving a kidney from the national supply, and need for antibody induction. Most importantly, DGF was associated with worse outcomes. PMID- 25131023 TI - Kidney retransplantation: removal or persistence of the previous failed allograft? AB - A significant percentage of patients with failed renal graft are candidates for retransplantation. The outcomes of retransplantation are poorer than those of primary transplantation and sensitization is documented to be a major reason. The management of a failed allograft that is not immediately symptomatic is still very controversial. The aim of this study was to determine the impact of the failed allograft nephrectomy on a subsequent transplantation and its importance in the sensitization. We performed a retrospective analysis of the local prospective transplantation registry of the outcome of 126 second kidney transplantations among 2438 transplantations performed in our unit between June 1980 and March 2013, comparing those who underwent allograft nephrectomy prior to retransplantation with those who retained the failed graft. Primary endpoints were graft and patient survival. The levels of panel-reactive antibodies (PRA) and rate of acute rejections on retransplantation outcomes were also studied. Among the 126 patients who underwent a second renal transplantation, 76 (60.3%) had a prior graft nephrectomy (Group A), whereas 50 (39.7%) kept their failed graft (Group B). Group A showed significantly more positive PRA levels when compared with the other group (38% vs 10%; P < .001), as measured before the most recent transplantation, and a higher rate of acute rejection (19% vs 5.6%; P = .016). There were 28 (36%) renal allograft losses for Group A and 18 (36%) for those who had not had transplantectomy (P = not significant [NS]). One-, 3-, and 5-year graft survival rates were 96.6%, 90.7%, and 83.4%, respectively, in Group A and 95%, 82%, and 68.4%, respectively, in Group B, with no statistical differences (P = .19). Five-year actuarial patient survival rates in the 2 groups was 89.3% and 82.8%, respectively (P = .55). Multivariate analysis showed that PRA level and delayed graft function (DGF) had a statistically significant influence on graft survival (P = .028; odds ratio [OR] = 1.029; and P = .024; OR = 8.6), irrespective of whether the patient had graft nephrectomy or not. The allosensitization indicated by PRA increases after transplantectomy and leads to a higher incidence of acute rejection after retransplantation. Nephrectomy of failed allograft does not seem to significantly influence the survival of a subsequent graft. The decision to remove or retain a failed graft in the context of retransplantation should thus be based on known clinical indications for the procedure. PMID- 25131024 TI - Post-transplantation weight gain: prevalence and the impact of steroid-free therapy. AB - INTRODUCTION: Weight gain after renal transplantation has a multifactorial etiology, which can be associated with complications such as hypertension, dyslipidemia and diabetes, with a probable impact on cardiovascular morbidity and mortality post-transplantation. OBJECTIVE: The objectives of this study were to investigate the prevalence of weight gain and obesity post-transplantation among renal recipients of a hospital and to evaluate the impact of immunosuppressive therapy without steroids. MATERIALS AND METHODS: We have evaluated all patients who had kidney transplantations performed between January 2005 and December 2009 at General Hospital of Fortaleza, who were older than 18 years of age and had at least 12 months of follow-up post-transplantation. Overweight was defined as body mass index (BMI) between 25 and 30 kg/m(2) and obesity >30 kg/m(2). The association between weight gain and the following variables was investigated: age and gender of the recipient and the donor, donor type, steroid use, presence of systemic arterial hypertension (SAH) and diabetes mellitus, creatinine, glucose, cholesterol, and triglycerides. RESULTS: The study population included 203 recipients; 59.5% were males, their mean age systemic arterial hypertension (SAH) was 37 years, and 64.2% had deceased donors. In regard to immunosuppression, 41.3% made use of steroids. After 36 months of follow-up, the average weight gain was 6.6 kg in relation to the first month post-transplantation. Among the variables studied, the recipient's younger age and female gender, the younger donor, and the creatinine level were associated with greater weight gain after 36 months of transplantation. CONCLUSION: The percentage of weight gain was on average 9% after 36 months post-transplantation, although the prevalence of overweight and obesity increased significantly in the same period. The use of steroid therapy had no impact on the percentage of weight gain post transplantation, and association was observed only between the younger age and the female gender of the recipient, the younger donor age, and the creatinine level with the highest weight gain post-transplantation. PMID- 25131025 TI - Metabolic surgery for the treatment of type 2 diabetes in pancreas after kidney transplant candidates. AB - Metabolic surgery for the treatment of type 2 diabetes mellitus (T2DM) in patients not morbidly obese (BMI <35) has been widely studied. Taking into account that ~12% of pancreas transplants are performed in patients with T2DM, our goal was to evaluate the impact of metabolic surgery on the management of obese patients with T2DM on waiting lists for a pancreas transplant. We performed a Roux-en-Y gastrointestinal bypass in 5 patients with insulin-dependent T2DM who were candidates for pancreas after kidney transplant and with a BMI <35. Three patients became insulin independent by the end of the first year while the other 2 reduced their insulin requirements by 70%. Furthermore, all patients achieved improved control of lipid levels. We concluded that the surgery was effective in controlling blood glucose and lipid metabolism in these obese T2DM kidney transplant recipients. In this population, a pancreas transplant, along with its associated morbidity, may be avoided. PMID- 25131026 TI - Fatigue effects in daily life activities of kidney transplant recipients. AB - After undergoing kidney transplantation, some patients still face one symptom that continues after the dialysis sessions: fatigue (physical and mental tiredness that does not get better after resting). Fatigue effects in the everyday lives of kidney transplant patients can be beneficially modified early by changing this scenario. This is a quantitative study about the intensity and impacts of fatigue in kidney transplant patients admitted to the Hypertension and Kidney Hospital from October 2011 to March 2012. The fatigue pictogram was used to evaluate the level of fatigue interference in the daily life activities of kidney transplant patients. The sample consists of 39 patients, and was developed in 2 phases: data collection and attendance after and before the transplantation until hospital discharge. Descriptive statistical analyses were used. In the group at issue, we have noticed the following profile of the sample: 84.3% of transplantations with live donors, most were men, average age 36.5 years old, average hospitalization time 11.1 days, average time of renal failure 66.4 months, systemic arterial hypertension prevalence 66.7%, and the prevalence of at least 1.8 diseases in each individual. The self-referred causes of chronic renal failure were uncontrolled systemic arterial hypertension, glomerulonephritis, and overuse of anti-inflammatory drugs, among others. The study shows that fatigue is directly related to the level of activities of daily living, causing less ability to perform activities in the higher level of fatigue, which is in the immediate postoperative period and only settling fully on the 9th postoperative day. PMID- 25131027 TI - Body mass index in the first year after kidney transplantation. AB - INTRODUCTION: Kidney transplant recipients (KTR) experience better appetite, partly due to the use of steroids, and are subjected to less severe dietetic restrictions, hence they tend to increase the uptake of calories, which favors weight gain posttransplantation. In this study, we evaluate the profile of body mass index (BMI) in the first year posttransplantation. METHODS: This was a retrospective study including 131 patients who received transplants between 1991 and 2011. We collected demographic and clinical data such as body weight and height, and calculated BMI pretransplantation and at 6 and 12 months posttransplantation. RESULTS: Mean age was 47.1 +/- 13.1 years, 64.9% were male, and 29% of patients were diabetic. Pretransplantation mean BMI was 23.04 +/- 4.08 kg/m(2), and at 6 and 12 months posttransplantation it increased to 24.55 +/- 4.2 kg/m(2) and 24.65 +/- 4.16 kg/m(2), respectively (P < .001). At 6 months, this significant weight gain occurred in all patients, even those malnourished, eutrophic, overweight, and obese at pretransplantation. Looking at pretransplantation malnourished patients, 30.8% remained malnourished 1 year after transplantation. Otherwise, 28.6% of pretransplantation overweight patients and 100% of pretransplantation obese patients could be classified as obese at 1 year posttransplantation. CONCLUSIONS: Increase in BMI is common in obese and nonobese KTR. This study highlights the importance of identifying subjects at risk for excessive weight gain posttransplantation, thus allowing an early nutritional intervention to prevent its complications. PMID- 25131028 TI - Outcome of bacteremia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae after solid organ transplantation. AB - INTRODUCTION: Although infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) has been recognized as an important cause of morbidity after solid organ transplantation, there are limited data on the outcome of this complication among transplant recipients. The objective of this study was to describe the outcome and factors associated with mortality among recipients of abdominal solid organ transplants with bloodstream infection caused by ESBL-E. PATIENTS AND METHODS: This study was a retrospective analysis of a case series of patients who had bacteremia caused by ESBL-E after undergoing renal or liver transplantation between January 2000 and September 2008 at a university-affiliated hospital in Rio de Janeiro, Brazil. The primary end point of the study was death within 30 days of the diagnosis of bacteremia. RESULTS: During the study period, 997 subjects underwent kidney (759 patients) or liver (238 patients) transplantation. Fifty-four episodes of bacteremia caused by ESBL E were diagnosed in 39 patients (4%). Mortality after the first episode of ESBL-E bacteremia was 26% (10 deaths). In multiple logistic regression analysis, the Pitt bacteremia score (P = .005) and being on mechanical ventilation at the time of infection diagnosis (P = .02) were the only variables associated with mortality. Thirteen episodes of recurrent bacteremia occurred in 8 (28%) of the 29 patients who survived the first episode. Two (25%) of these 8 patients died during the course of a recurrent episode. CONCLUSIONS: Bacteremia caused by ESBL E was associated with high mortality and high risk of recurrence. Factors associated with clinical severity at the time of infection diagnosis were the main predictors of mortality. PMID- 25131029 TI - Urinary tract infection in renal transplant recipients: incidence, risk factors, and impact on graft function. AB - INTRODUCTION: Urinary tract infection (UTI) is the most common infection posttransplant. However, the risk factors for and the impact of UTIs remain controversial. The aim of this study was to identify the incidence of posttransplant UTIs in a series of renal transplant recipients from deceased donors. Secondary objectives were to identify: (1) the most frequent infectious agents; (2) risk factors related to donor; (3) risk factors related to recipients; and (4) impact of UTI on graft function. PATIENTS AND METHODS: This was a retrospective analysis of medical records from renal transplant patients from January to December 2010. Local ethics committee approved the protocol. RESULTS: The incidence of UTI in this series was 34.2%. Risk factors for UTI were older age, (independent of gender), biopsy-proven acute rejection episodes, and kidneys from deceased donors (United Network for Organ Sharing criteria). For female patients, the number of pretransplant pregnancies was an additional risk factor. Recurrent UTI was observed in 44% of patients from the UTI group. The most common infectious agents were Escherichia coli and Klebsiella pneumoniae, for both isolated and recurrent UTI. No difference in renal graft function or immunosuppressive therapy was observed between groups after the 1-year follow-up. CONCLUSIONS: In this series, older age, previous pregnancy, kidneys from expanded criteria donors, and biopsy-proven acute rejection episodes were risk factors for posttransplant UTI. Recurrence of UTI was observed in 44%, with no negative impact on graft function or survival. PMID- 25131030 TI - MELD score and albumin replacement are related to higher costs during management of patients with refractory ascites. AB - BACKGROUND: Ascites is the most common complication of cirrhosis and indicates that the disease is at an advanced stage. In cirrhotic patients with refractory ascites, treatment is based on repeat paracentesis. The objective of this study is to evaluate the cost of paracentesis in cirrhotic patients and to determine the factors related to this cost. METHODS: This prospective study included all patients with cirrhosis who underwent paracentesis between March 2012 and March 2013 at the Outpatient Service of the Liver Transplantation Unit, Clinical Hospital, University of Sao Paulo School of Medicine. Microcost analysis was performed with individual tabbed data regarding the consumption of albumin and containers for ascites. The remaining cost components were drugs, materials used during the procedure, and human resources. Statistical analysis was performed using SPSS version 20. RESULTS: We conducted a total of 881 paracentesis procedures in a group of 155 patients that included 60.5% men and 39.5% women with a mean age of 57 years (range 20 to 80 years). Patients underwent an average of 5.3 paracentesis procedures per year (range 1 to 32). The total cost of all procedures was $193,126.60 and the most costly component was albumin ($87,162.10). The average cost per procedure was $219.50. The most frequent liver disease diagnoses were hepatitis C (24%) and alcoholic cirrhosis (24%). The majority of patients were on the liver transplant list (54.2%). Factors associated with higher costs in the period were a Model for End-Stage Liver Disease score higher than 24 (P = .001) and patients on the transplant waiting list (P = .042). CONCLUSIONS: Paracentesis in cirrhotic patients is a high-cost procedure in health care. The main factors related to cost are the volume of fluid drained due to the need for albumin replacement and the severity of liver disease that is related to the frequency of paracentesis. PMID- 25131031 TI - Liver transplantation for unresectable hepatocellular carcinoma in elderly patients: what to expect. AB - INTRODUCTION: Elderly patients have orthotopic liver transplantation (OLT) outcomes comparable to younger individuals. However, it is undefined whether such results are also seen in those with unresectable hepatocellular carcinoma (HCC). The primary endpoints of this study were overall survival (OS), retransplantation rate, and disease-free survival (DFS) in OLT recipients with HCC and aged >=65 years compared with those aged <65 years. PATIENTS AND METHODS: This was a single center retrospective review of a cohort of adult deceased-donor OLT recipients due to unresectable HCC within the Milan criteria from May 2006 through March 2013. Demographic and clinical variables and outcomes of patients aged >=65 years were compared with those aged <65 years. RESULTS: Thirty-seven individuals >=65 years of age (group 1) and 141 individuals <65 years of age (group 2) were analyzed. OS (group 1 vs group 2) at 1 year (78% vs 81%), 3 years (64% vs 70%), and 5 years (64% vs 66%) (P = .49) was comparable. Retransplantation rates were also similar (group 1: 13.5%; group 2, 10.6% [P = .61]). DFS (group 1 vs group 2) at 1 year (100% vs 95%), 3 years (91% vs 92%), and 5 years (91% vs 92%) (P = .56) was also not significantly different between groups. On multivariate analysis, age >65 years was not an independent predictor of OS or DFS. CONCLUSIONS: Patients aged >=65 years with HCC presented with outcomes similar to their younger counterparts. Chronologic age is not a good predictor of outcome, and transplantation is feasible if overall clinical conditions and comorbidities allow. PMID- 25131032 TI - Surface electromyography for respiratory assessment of liver transplant candidates, healthy subjects and after chevron post-operative incision. AB - BACKGROUND: Surface electromyography is a noninvasive technique for detecting the activity of skeletal muscles and especially the muscles for respiratory compliance; namely, the diaphragm and rectus abdominis. This study compares these muscles in healthy individuals, liver disease patients, and after abdominal surgery. OBJECTIVE: To study muscle activity by surface electromyography of the right diaphragm muscles and right rectus abdominis (root means square, RMS), and the manovacuometry muscle strength (maximal inspiratory pressure, MIP; and maximal expiratory pressure, MEP). RESULTS: We evaluated 246 subjects who were divided into 3 groups: healthy (65), liver disease (171), and post-surgery (10). In liver disease group the BMI was higher significantly for ascites (P = .001), and was increase in RMS rectum (P = .0001), RMS diaphragm (P = .030), and a decreased inspiratory and expiratory indices (P = .0001) pressure in the post surgery group. A multivariate analysis showed tendency to an increased BMI in liver disease and in the post-surgery groups correlated with an increased RMS rectum and the lower MIP/MEP (P = .11). The receiver operating characteristic curve showed that RMS rectus was capable of discriminating liver disease and post surgery patients from healthy subjects (area = 0.63; 95% CI 0.549-0.725). CONCLUSION: The muscle activity of normal individuals is lower than in subjects with deficit muscles because less effort is necessary to overcome the same resistance, observed by surface electromyography and muscle strength. PMID- 25131033 TI - Evaluation of functional status, pulmonary capacity, body composition, and quality of life of end-stage liver disease patients who are candidates for liver surgery. AB - INTRODUCTION: Muscular weakness in combination with malnutrition can induce a global motor impairment and physical inactivity, adversely impairing the daily living activities and quality of life of end-stage liver disease patients who are candidates for liver transplantation. OBJECTIVES: To evaluate functional status, pulmonary capacity, body composition and quality of life in end-stage liver disease patients who are candidates for liver transplantation; to verify if there is a correlation between the functional variables of the individuals tested through the 6-minute walk test (6MWT) and covariables: pulmonary function test (PFP), quality of life and body composition. METHODS: This study was carried out at the Liver Transplantation Unit of the State University of Campinas (UNICAMP). We included 46 patients with end-stage liver disease who underwent the following evaluations: medical history, quality of life questionnaire "Short Form 36" (SF 36), surface electromyography (sEMG) of the diaphragm and rectus abdominis muscles, body composition assessment by electrical vioimpedance (BIA), 6MWT and PFP. RESULTS: Univariate analysis and Pearson's correlation found correlations between distance walked on 6MWT and QOL (P = .006 and P = .02) and TBW (P = .5 and P = .02). Pearson's correlation were found between respiratory variables of 6MWT, QOL, and PFP. CONCLUSION: The functional status may be correlated to body composition, quality of life and pulmonary capacity of patients with liver disease, candidates for transplantation. PMID- 25131034 TI - Effects of a respiratory physiotherapeutic program in liver transplantation candidates. AB - BACKGROUND: Candidates for liver transplantation may have malnutrition, fatigue, loss of muscle mass and function. The combination of these factors leads to overall physical disability and physical inactivity. OBJECTIVE: The aim of the study was to evaluate the effects of a respiratory physiotherapeutic program on liver transplantation candidates. METHOD: Forty-two patients were evaluated by respiratory muscle strength, surface electromyography of the rectus abdominis and diaphragm, and spirometry. We also applied the SF-36. The patients were divided into two groups: 12 randomly assigned to the control group and 5 in the intervention group. The intervention consisted of an explanatory and illustrative manual to be followed at home with diaphragmatic breathing exercises, diaphragmatic isometric exercise, Threshold IMT, lifting the upper limbs with a bat, and strengthening the abdominals. RESULTS: Significant difference was found between initial forced expiratory flow (FEF)25-75% (P = .042) and final FEF25-75 in the intervention group. The control group had significant difference (P = .036) in the diaphragm RMS between initial time and end time. In conclusion, the control group showed greater electrical activity of the diaphragm after 3 months. CONCLUSION: The intervention group benefited from the exercise, thus improving the FEF25-75%. PMID- 25131035 TI - Clinical evaluation of hepatic transection on pediatric liver transplantation. AB - OBJECTIVES: Liver transplantation is an effective technique in the treatment of end-stage liver disease. The aim of this study was to evaluate the impact of hepatic transection, an advanced surgical technique able to tailor size to generate two grafts to from a single donor. MATERIALS AND METHODS: A retrospective study between January 2000 and September 2013, reviewing 91 pediatric patients who underwent 96 liver transplants from deceased donors. Patients were distributed into two groups: whole organ (WO, n = 39) and transected liver grafts (TLG, n = 57). The following were evaluated: etiology, anthrophometric parameters (age, weight, height, z score weight/age, and height/age), model for end-stage liver disease (MELD) or pediatric end-stage liver disease (PELD), previous surgeries, transfusion of blood components, 1-year survival rate, preoperative laboratory testing, from the second and seventh postoperative days, lactate during surgery, postoperative complications, duration of surgery, duration of cold and warm ischemia, types of biliary reconstruction, and laboratory testing of the donor. RESULTS: The anthropometric values showed significant differences (P < .05) between the groups. The average age was 124.7 months in the WO group and 33.6 months in the TLG group (P < .0001), while the weight was 28.0 kg and 7.4 kg, respectively (P < .0001). The analysis of z score weight/age showed that the TLG had greater acute and chronic malnutrition, probably due to the etiology of liver disease, present from birth in patients as young. Red blood transfusion was higher in the TLG group (P < .0006) due to the cut surface of the graft, emphasizing the use and improvement of hemostatic techniques. CONCLUSION: Despite differences between the groups, clinical and surgical complications were similar, showing that liver transection injury didn't change the results of transplantation. There was no impact on liver function, graft, or 1-year patient survival after liver transection. Second postoperative lactate is a predictive factor of death. Transection liver transplantation is an effective method as an alternative to pediatric liver transplantation. PMID- 25131036 TI - Grade IV fibrosis interferes in biliary drainage after Kasai procedure. AB - OBJECTIVES: Biliary atresia (BA) is the most common cause of liver transplantation in children. The earlier the treatment is done, the better the prognosis. The aim is to evaluate the impact of late diagnosis in children with BA, including the histopathological findings and success rate of biliary drainage in patients submitted to hepatic portoenterostomy (HPE). MATERIALS AND METHODS: A retrospective study of cases of BA in the Department of Pediatric Surgery, Federal University of Sao Paulo (UNIFESP) between 1998-2011. We found 63 cases of BA; of these, 42 underwent HPE and 21 were referred for liver transplantation. Clinic and pathologic data were evaluated. RESULTS: The HPE was performed with a mean age of 86.5 days, with 16.6% having the operation at 60 days or earlier; 59.2% between 61 and 90 days; and 23.8% after 90 days. Successful biliary drainage occurred in 31% of surgeries, Mean days when HPE drained was 69.1 days, and 94.3 days when the surgery did not drain (P = .05). All patients who were successfully drained, did not have grade IV fibrosis on histology. In cases in which surgery was performed after 60 days that had not drained, 25% had grade IV fibrosis on biopsy (P = .0469). CONCLUSION: The age of HPE relates to better prognosis of the disease. It was found that the rate of grade IV fibrosis is higher in no drainage patients. All patients with grade IV fibrosis had no biliary drainage. PMID- 25131037 TI - Comparative morphometric analysis of 5 interpositional arterial autograft options for adult living donor liver transplantation. AB - In living donor liver transplantation, the right-sided graft presents thin and short vessels, bringing forward a more difficult anastomosis. In these cases, an interpositional arterial autograft can be used to favor the performance of the arterial anastomosis, making the procedure easier and avoiding surgical complications. OBJECTIVE: We compared the inferior mesenteric artery (IMA), the splenic artery (SA), the inferior epigastric artery (IEA), the descending branch of the lateral circumflex femoral artery (LCFA), and the proper hepatic artery (PHA) as options for interpositional autograft in living donor liver transplantation. METHOD: Segments of at least 3 cm of all 5 arteries were harvested from 16 fresh adult cadavers from both genders through standardized dissection. The analyzed measures were proximal and distal diameter and length. The proximal diameter of the RHA and the distal diameter of the SA, IMA, IEA and the LCFA were compared to the distal diameter of the RHA. The proximal and distal diameters of the SA, IEA and LCFA were compared to study caliber gain of each artery. RESULTS: All arteries except the IMA showed statistical significant difference in relation to the RHA in terms of diameter. Regarding caliber gain, the arteries demonstrated statistical significant difference. All the harvested arteries except PHA were 3 cm in length. CONCLUSION: The IMA demonstrated the best compatibility with the RHA in terms of diameter and showed sufficient length to be employed as interpositional graft. The PHA, the SA, the IEA and the LCFA presented statistically significant different diameters when compared to the RHA. Among these vessels, only the PHA did not show sufficient mean length. PMID- 25131038 TI - Is there a relationship between intraoperative hemodynamic instability and calcineurin inhibitor-related toxicity, early after liver transplantation? A single-center observational study. AB - This study evaluated the relationship between intraoperative hemodynamic instability (IOHI) and the development of calcineurin inhibitor (CNI) toxicity in the early postoperative period after liver transplantation (LT). Eighty-two patients were enrolled during a 1-year period and a 3-month follow-up. IOHI, requiring continuous infusion of vasopressors, was observed in 31 patients (38%, group 1; control group 2, n = 51). Acute kidney injury (AKI) developed in 28 patients (52% in group 1 vs 24% in group 2, P = .02), and CNI-related neurotoxicity (CNI-NT) in 26 (48% in group 1 vs 22% in group 2, P = .03). Group 1 patients received mainly deceased donor grafts (87% vs 57% in group 2, P < .001). An independent association between IOHI and CNI-NT (P = .029) and AKI (P = .016) was observed. The receiver-operator characteristic curve revealed an area under the curve of 0.63 for IHI (sensitivity 56%; specificity 75%) and 0.65 for AKI (sensitivity 56%; specificity 70.2%). In conclusion, patients undergoing LT with IOHI may be more prone to developing CNI-NT and AKI in the early postoperative period. PMID- 25131039 TI - Ten-year experience with liver transplantation for hepatocellular carcinoma in a Federal University Hospital in the Northeast of Brazil. AB - Hepatocellular carcinoma (HCC) is the most frequent and important primary liver tumor, with annual worldwide incidence of over 1 million cases, accounting for at least 500,000 deaths per year. The majority of cases of HCC occur in the setting of liver cirrhosis. In this retrospective, descriptive, and analytical study, between May 2002 and April 2012, 664 liver transplantations (LT) were conducted at a Federal University Hospital in the Northeast of Brazil, among which 140 LT were performed in patients with HCC. The tumor was more frequent in men with an average age of 56 years and infected with hepatitis C virus, many with a history of alcohol abuse. Alpha-fetoprotein was not useful in the diagnosis, and imaging methods have failed to diagnose the nodules in 19 patients (13.6%). Transarterial chemoembolization was the most-used bridging therapy to inhibit tumor growth for patients with HCC eligible for transplantation. The implementation of the Model for End Stage Liver Disease score in 2006 brought benefits to these patients. The rate of HCC recurrence after LT was 8.57% and occurred more often in the first 2 years after transplantation, with the liver graft being the most common site. Significant risk factors for recurrence were a long time on the LT waiting list, number of liver nodules over 3.5, and the presence of vascular invasion. In conclusion, LT for HCC leads to excellent long-term survival, with relatively few patients dying from tumor recurrence. PMID- 25131040 TI - Response to transarterial chemoembolization in candidates with hepatocellular carcinoma within Milan criteria does not predict post-transplant disease-free survival. AB - INTRODUCTION: Few groups have studied the impact of pretransplant transarterial chemoembolization (TACE) in the outcomes of liver transplant recipients with hepatocellular carcinoma (HCC). We verified whether response to TACE in HCC candidates impacts post-transplant disease-free survival. METHODS: This a single center retrospective study of patients who underwent liver transplantation from 2006-2013. Included were those transplanted due to HCC within the Milan criteria who were treated with TACE in the pre-transplant period. Response to TACE followed the modified RECIST (mRECIST) criteria. Disease free-survival was the main endpoint of the study. RESULTS: We included 187 patients in this study. The population had an average age of 57.5 years, predominantly formed by men (82.5%), with an average IMC of 26.7, MELD of 13, with viral hepatitis as main cause of liver disease. Average waiting time was 253 days and follow-up was 27.3 months. Based on response to TACE, 3-year disease-free survival was 84.1% for those with complete response to TACE, 84.1% for those with partial response to TACE, 85.7% for those with stable disease and 100% for patients with progressive disease. Multivariate analysis did not identify response to TACE as a predictor of disease free post-transplant survival. CONCLUSIONS: Response to TACE in candidates with HCC within Milan criteria does not predict post-transplant disease-free survival. PMID- 25131041 TI - Results from a liver transplant center in northeastern Brazil that performed more than 100 transplants in 2011. AB - BACKGROUND: Orthotopic liver transplantation is an essential approach performed in several centers around the world. Our center lies in northeastern Brazil and has performed this procedure since 2002. In 2011, 126 liver transplants were performed at our institution. METHODS: This study is a retrospective and descriptive analysis of the data collected from the medical records of those transplants. Epidemiological and clinical aspects were considered in this evaluation. The outcome analysis considered overall survival rates within 30 days and 1 year after transplantation. RESULTS: The sample of 124 patients showed 60% of all patients came from other regions, particularly the North and Midwest regions of Brazil, which had a combined population of >30 million in 2011. The most frequent etiologies for end-stage liver disease were hepatitis C and alcoholism. The average calculated MELD (Model for end-stage liver disease) was 21.0. Patient survival curves were 88.4% after 30 days and 81.5% after 1 year. CONCLUSION: The development of effective perioperative management for this procedure resulted in improved outcomes. Our center's performance is based on a multidisciplinary approach performed by qualified personnel, careful pre- and postoperative follow-up and continuous improvement of services. PMID- 25131042 TI - Effect of a physical exercise program on the functional capacity of liver transplant patients. AB - BACKGROUND: Recently there has been great concern about the quality of life and health of liver transplant patients (LTP). These patients often present with metabolic disorders, which can improve with regular physical exercise. The aim of this study was to investigate the effect of a physical exercise program on the functional capacity of LTP. METHOD: The distance walked in the 6-minute walk test and the resting energy expenditure (REE) were evaluated in 15 subjects who regularly attend the outpatient Bias Fortes Clinic at Universidade Federal de Minas Gerais. The patients were divided into 2 groups, the Exercise Group (EG) (6 men and 3 women; 52 +/- 15 years old, BMI 22.4 +/- 4.0 kg/m2) performed 24 sessions of continuous 30 min treadmill exercise. Intensity of exercise was increased from 50%-70% of the maximum heart rate over the training period. A group of 3 men and 3 women (39 +/- 15 years, BMI 24.5 +/- 4.4 kg/m2) served as controls (CG). RESULTS: After undergoing exercise training, patients in the EG showed a 19.4% increase in the distance walked (pre = 453.6 +/- 128.0 m and post = 582.5 +/- 90.1 m). Also, there was an increase in their REE (pre = 1,060.0 +/- 194.2 kcal and post = 1,375.0 +/- 258.6 kcal) (P < .05) indicating an increase in their exercise capacity and metabolic improvements. There were no differences in the distance walked (pre = 516.5 +/- 62.0 m and post = 517.7 +/- 71.9 m) and REE (pre = 1,393.0 +/- 213.3 kcal to post = 1,465.0 +/- 170.3 kcal) (P > .05) for CG. Our results are in agreement with previous studies. CONCLUSIONS: We conclude that the exercise program promoted significant improvements in functional capacity. These findings have positive implications for the control of metabolic diseases, which are common in patients after liver transplantation. PMID- 25131043 TI - Use of IGL-1 preservation solution in liver transplantation. AB - University of Wisconsin (UW) solution has been known as the standard solution for liver graft preservation. Alternative preservation solutions have been used in liver transplantation, such as histidine-tryptophan-ketoglutarate (HTK) and Celsior solution. Institut Georges Lopez-1 (IGL-1) is a new preservation solution with lower potassium and lower viscosity than UW solution that has recently been used in liver transplant. Data from 178 patients who received transplants from August 2008 to June 2013 at Hospital Santa Isabel, Blumenau, Brazil, were analyzed. All patients received grafts from brain death donors. In November 2011 we started to use IGL-1 as an alternate preservation solution. Therefore, 53 patients using IGL-1 preserved grafts were compared to 125 using HTK solution. The donor age in the HTK group ranged from 11-77 years, with a mean of 43.4 +/- 4.8. In the IGL-1 group donor age ranged from 9-62 years, with a mean of 35.8 +/- 4.5. Cold ischemia time in the HTK group ranged from 85-1145 minutes, mean 443.5 +/- 183.5 minutes. In the IGL-1 group, cold ischemia time ranged from 85-670 minutes, mean 329.3 +/- 134.8 minutes. The overall operative mortality rate was 14% (25 patients); in the HTK group, 14.4% (18 patients); and in the IGL-1 group, 13.4% (7 patients). One graft in the HTK group presented with primary non function (PNF), 0.7%; there were none in the IGL-1 group. In our study, IGL-1 has been shown to be safe to use as a preservation solution for liver transplantation. Early post-transplant graft function was comparable to that observed with HTK solution, although a tendency for lower alanine aminotransferase levels was noticed. IGL-1 has been shown to be safe, cost efficient, and an effective preservation solution. PMID- 25131044 TI - Is urinary gamma-glutamyl transpeptidase superior to urinary neutrophil gelatinase-associated lipocalin for early prediction of acute kidney injury after liver transplantation? AB - In this prospective study, we comparatively evaluated the accuracy of several biomarkers of acute kidney injury (AKI) on predicting its occurrence after liver transplantation (LT). The parameters evaluated were urinary tubular enzymes (gamma-glutamyl transpeptidase [gammaGT], alkaline phosphatase, and urinary lactate dehydrogenase) and urinary neutrophil gelatinase-associated lipocalin. These parameters were evaluated both as isolated variables and divided by urinary creatinine. Samples were collected by the end of surgery (determination 1) and at 12 to 24 hours after surgery (determination 2). The study endpoint was the development of AKI. The study was performed over a 1-year period, and 61 of 77 patients were enrolled (main exclusion criteria were perioperative death, previous known renal failure, and insufficient data for analysis). Of these 61 patients, AKI was observed in 19 (group 1). The main relevant parameter to predict AKI was the absolute value of urinary gammaGT at determination 1 (area under the curve, 0.74; specificity, 72.5%; sensitivity, 70.3%; cutoff, 36 U/mL). Urinary neutrophil gelatinase-associated lipocalin was not as accurate; the best predicted value for this parameter was absolute value at D1 with an area under the curve of 0.5 (specificity, 84.2%; sensitivity, 35.7%; cutoff value, 44.6 ng/mL). We concluded that the absolute value of urinary gammaGT evaluated at the end of LT was the most accurate parameter to predict AKI in our cohort. Urinary enzyme levels must be taken into account in future analysis of this issue. PMID- 25131045 TI - Acute kidney injury after liver transplantation: incidence and mortality. AB - INTRODUCTION: Patients undergoing orthotopic liver transplantation often present with acute kidney injury (AKI) in the postoperative period. It has been associated with a greater number of complications and high mortality rates. The goal of this study was to determine the incidence of AKI during the early posttransplant period and mortality in patients undergoing orthotopic liver transplantation in our hospital. PATIENTS AND METHODS: In this retrospective cohort study, we reviewed the medical records of all patients aged >18 years undergoing liver transplantation from April 2008 to April 2011. The exclusion criteria were a glomerular filtration rate (estimated by using the Modification of Diet in Renal Disease formula) <60 mL/min/1.73 m(2) or AKI at the time of transplantation. AKI was defined as an increase >=50% from preoperative baseline serum creatinine levels during the hospitalization period. RESULTS: Of 113 selected patients, 78 (69%) were male. The mean age was 54.03 +/- 9.38 years. The mean preoperative baseline creatinine level was 0.94 +/- 0.15 mg/dL, and the estimated glomerular filtration rate was 87.09 +/- 19.67 mL/min/1.73 m(2). The mean calculated Model for End-Stage Liver Disease score was 13. Hepatitis C serology was present in 70.8%, hepatitis B in 11.5%, hepatocellular carcinoma in 75.2%, and alcohol abuse in 31.9% of patients. The incidence of AKI was 56.6% (64 of 113 patients). The main risk factors for AKI were Model for End-Stage Liver Disease score and diuretic use at baseline. Renal replacement therapy (RRT) was performed in 19.5% (22 of 113) of patients. The hospital mortality rate in the group with AKI was 25% (16 of 64 patients) and 6.1% (3 of 49 patients) between patients without AKI (odds ratio, 5.11 [confidence interval, 1.39-18.7]; P < .01]. Among patients who underwent RRT, the in-hospital mortality rate was 54.5% (12 of 22 patients) compared with 7.7% (7 of 91 patients) from the other remaining patient cohort (odds ratio, 14.40 [confidence interval, 4.60-45.00]; P < .01). CONCLUSIONS: There was a high incidence of AKI in patients undergoing liver transplantation and an increased risk of mortality among patients who needed RRT. PMID- 25131046 TI - Relevance of anxiety and stress levels on sleep quality after liver transplantation. AB - The goal of this study was to assess the effects of anxiety and stress on sleep quality in liver transplantation recipients. A prospective cross-sectional study was performed including 45 recipients enrolled at a liver transplantation program at Ribeirao Preto, State of Sao Paulo, Brazil. Anxiety and stress were evaluated by using a reduced version of the State-Trait Anxiety Inventory and the Perceived Stress Scale, respectively. Sleep quality and excessive daytime sleepiness were evaluated by using the Brazilian Portuguese versions of the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale. Thirty-two (71.11%) recipients presented with compromised sleep quality and 5 (11.11%) presented with excessive daytime sleepiness. Recipients with bad sleep quality had anxiety (mean, 26.91 points) and stress (mean, 17.88 points) levels that were higher than the levels of patients with normal sleep quality patterns, with anxiety levels presenting with statistically significant differences (P = .0420). Patients with above average stress levels also had increased anxiety (mean, 28 points) and compromised sleep quality (mean, 7.03 points). In conclusion, a liver transplantation recipient who experiences bad sleep quality also has higher levels of anxiety and stress, suggesting a relationship between the sleep wakefulness cycle and anxiety/stress. Planning strategies aimed at reducing such emotional shifts among recipients is of paramount importance. Therefore, new strategies focusing on improving the sleep pattern of patients are necessary because unhealthy sleep behavior may impair postoperative recovery. PMID- 25131047 TI - Risk factors of pancreatic graft loss and death of receptor after simultaneous pancreas/kidney transplantation. AB - Simultaneous pancreas/kidney transplants require a long graft survival and the recipient to present with more benefits than risks. We evaluated the risk factors of receptor's death and pancreatic graft loss on 2 occasions (3 and 12 months' postoperatively) in 292 transplants in whom 22 variables were evaluated. Variables were selected, 9 receivers, 8 donors, and 5 variables related to the surgical procedure. All independent variables were compared with the dependent variables of pancreatic graft losses and patient deaths. Those considered significant according to univariate analysis were analyzed by using multiple logistic regression techniques in an attempt to develop a mathematical model capable of predicting both pancreatic graft and patient losses. Lastly, based on the resulting models with all significant variables, scores were created to determine the risk of patient death and pancreatic graft loss. In the adjusted multivariate analysis, the significant variables were donor age, receiver's body mass index, initial pancreas implant, iliac venous drainage, and use of induction therapy related to pancreatic loss within 3 months after transplantation. Independent risk factors regarding the loss of patients within 12 months were body mass index and receptor induction therapy. The variables related to pancreatic graft loss within 3 months were donor age, receiver body mass index, initial use of pancreatic graft, iliac venous drainage, and induction therapy; these variables can be used for creating a risk score. The donor body mass index and the induction therapy were independently related to patient loss within 12 months after the transplant. PMID- 25131048 TI - Component analysis of hospital cost of pancreas-kidney transplant and correlations with different variables in a Brazilian hospital. AB - INTRODUCTION: Simultaneous pancreas-kidney transplantation is associated with a high rate of complications when it is compared with transplantation of other organs; these increased complications can result in increased financial costs of the procedure. The objective of this study was to determine operating costs and financial results of simultaneous pancreas-kidney transplantation and its different variables in a Brazilian hospital. PATIENTS AND METHODS: Between January 2008 and December 2011, the monthly costs of 105 patients were calculated. These patients were divided into 2 groups; the first consecutive 53 patients were labeled group I and the second set of 52 patients were labeled group II. The cost evaluation was made in US dollars. RESULTS: A total of 89 patients corresponded to the public health system and 16 patients to the supplementary health system. The percentage of hospital discharge was 92.4%. There was an increase in operating room costs in group II compared with group I with no statistically significant difference ($18,749.33 for group I and $17,608.26 for group II). The outcome of the operation was positive; it was greater for group II than for group I ($16,303.22 vs $3494.53). CONCLUSIONS: Simultaneous pancreas-kidney transplantation is a financially feasible procedure in Brazil, with the public health system being the main payment source. PMID- 25131049 TI - Home parenteral nutrition program and referral of potential candidates for intestinal and multivisceral transplantation in a single Brazilian center. AB - Intestinal failure is a multifaceted condition that may require high-complexity treatment and a multidisciplinary program, including home parenteral nutrition therapy (HPNT) and intestinal transplantation. In this article, we profile a Brazilian single-center experience with 128 cases of HTPN followed for the last 30 years and appraise the referral for potential intestinal and multivisceral transplantation. PMID- 25131050 TI - Heart transplantation in pediatric population and in adults with congenital heart disease: long-term follow-up, critical clinical analysis, and perspective for the future. AB - BACKGROUND: Heart transplantation is a treatment option for children as well as for adults with congenital heart disease. OBJECTIVE: To report the experience of a tertiary center with heart transplant program in pediatric population and in adults with congenital heart disease. PATIENTS AND METHODS: The study consisted of the evaluation of pediatric as well as adult patients undergoing heart transplantation for congenital heart disease. We evaluated the following indication and complications such as renal dialysis, graft vascular disease, tumors and survival. RESULTS: From October 1992 to November 2013, 134 patients had transplantation, and there were 139 transplantations and 5 retransplantations. The immunosuppression regimen is based on calcineurin inhibitors and cytostatic drugs. The type of heart disease indicated for transplantation was cardiomyopathies in 70% and congenital heart disease in 30%. Of these 134 patients, 85 patients were alive. Actuarial survival is 77.4%, 69.6%, 59.3% at 1, 5, and 10 years after transplantation. Three patients underwent renal transplantation, 1 patient is in renal dialysis, and 8.2% of patients had post-transplant lymphoproliferative disease. Two patients had retransplantation for graft vascular disease; 1 of them required a simultaneous kidney transplant and died 30 days after the procedure and 1 patient is clinically well 2 years after retransplantation. CONCLUSION: Heart transplantation in children and in adults with congenital heart disease is a promising therapeutic option and enables long-term survival for these patients. PMID- 25131051 TI - Posterior reversible encephalopathy syndrome in lung transplantation: 5 case reports. AB - Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiologic entity characterized by typical neurologic symptoms with characteristic cerebral image alterations. It has been reported in solid organ transplantations, especially related to the use of calcineurin inhibitors. The incidence of PRES in lung transplantation is unknown and probably under-reported in the literature. Here we describe 5 cases of PRES after bilateral lung transplantation. One of the reported cases was the first in the literature in which the neurologic onset precluded the introduction of calcineurin inhibitor. Therefore, although calcineurin inhibitors are known to play an important role in the development of PRES in the setting of lung transplantation, other causes seems to be involved in the physiopathology of this syndrome. PMID- 25131052 TI - Fungal infection by Mucorales order in lung transplantation: 4 case reports. AB - Mucorales is a fungus that causes systemic, highly lethal infections in immunocompromised patients. The overall mortality of pulmonary mucormycosis can reach 95%. This work is a review of medical records of 200 lung transplant recipients between the years of 2003 and 2013, in order to identify the prevalence of Mucorales in the Lung Transplantation service of Heart Institute (InCor), Hospital das Clinicas da Universidade de Sao Paulo, Brazil, by culture results from bronchoalveolar lavage and necropsy findings. We report 4 cases found at this analyses: 3 in patients with cystic fibrosis and 1 in a patient with bronchiectasis due to Kartagener syndrome. There were 2 unfavorable outcomes related to the presence of Mucorales, 1 by reduction of immunosuppression, another by invasive infection. Another patient died from renal and septic complications from another etiology. One patient was diagnosed at autopsy just 5 days after lung transplantation, with the Mucor inside the pulmonary vein with a precise, well-defined involvement only of donor's segment, leading to previous colonization hypothesis. There are few case reports of Mucorales infection in lung transplantation in the literature. Surveillance for the presence of Mucor can lead to timely fungal treatment and reduce morbidity and mortality in the immunocompromised patients, especially lung transplant recipients. PMID- 25131053 TI - Cardiac effect of ischemic preconditioning and heparin following intestinal ischemia and reperfusion in rats. AB - To study the role of heparin and ischemic preconditioning (IPC) in cardiac injury after intestinal ischemia (I) and reperfusion (R), 54 rats underwent 60 minutes of I, which was produced by occlusion of the superior mesenteric artery, and/or 120 minutes of R. The IPC group had the I procedure stimulation for 5 minutes and R for 10 minutes. The control group was subjected to sham surgery only, and the other groups were injected with saline solution (SS; 0.1 mL) or heparin (100 IU/kg) via the inferior cava vein 5 minutes before I and 5 minutes before R and 55 minutes after the R begins in I-R groups. In all animals, cardiac samples were stained with hematoxylin and eosin for optical microscopy analysis, and other sample was processed for lipid peroxidation determination. In I-R groups, both heparin and IPC showed significant protection compared to the SS group; conversely, in animals subjected only to I, no protection was observed. Moreover, when heparin was associated with IPC, I-R protection was compromised and the ischemic injury increased. Data showed that IPC and heparin attenuated cardiac dysfunction caused by intestinal I and I-R, but when used in association did not show beneficial effects. PMID- 25131054 TI - Ex situ regeneration of liver remnants hypothermically preserved for 24 hours. AB - INTRODUCTION: After partial hepatectomy (PH), the liver remnant (LR) shows a regenerative response, always keeping a percent relationship with the host. This process has been well described in the literature, but several aspects still need to be understood. There are no studies on hepatic LR regeneration during hypothermic preservation. Thus, the objective of the present study was to analyze LR regeneration after PH under conditions of hypothermal preservation. MATERIALS AND METHODS: Twenty adult Wistar rats were divided into 4 experimental groups: PHS (70% PH); PHP (70% PH of an organ perfused and preserved for 24 hours); PWL (perfused whole liver preserved for 24 hours); and NPWL (nonperfused whole liver). The liver was perfused with 250 mL Celsior solution with a catheter connected to a 1.30-cm-high liquid column. Hepatic tissue samples were submitted to immunohistochemical analysis for the evaluation of protein Ki67 expression, related to the mechanism of cell proliferation, to analysis of micro-RNA expression (miR-21 and miR-16) by real-time polymerase chain reaction, and to analysis of mitochondrial function. Nonparametric statistical analysis was used (P < .05). RESULTS: Ki67 analysis revealed that the PHP group showed 17.41% cell proliferation in LR (P < .01) compared to PHS (42.22%), PWL (11.43%), and NPWL (11.98%). miR-16 expression (proapoptotic) was found to be higher in the NPWL group compared to all others (PHS, PHP, and PWL), with a statistically significant difference between the NPWL group and the PHS and PHP groups. CONCLUSION: The animals submitted to PHS and PHP presenting greater Ki67 expression showed low miR-16 expression, indicating a low apoptotic index. In summary, the LR showed ex situ regeneration even under hypothermal conditions. There are no similar data in the literature surveyed. PMID- 25131055 TI - Ischemic preconditioning and atenolol on lung injury after intestinal ischemia and reperfusion in rats. AB - The aim of this study was evaluate the beta blocker atenolol (AT) and ischemic preconditioning (IPC) strategies for tissue protection against systemic effects of intestinal ischemia (I) and reperfusion (R) injury. Forty-two rats were pretreated with AT (1.5 mg . kg(-1)), 0.9% saline solution (SS; 0.1 mL), or IPC and then subjected to prolonged occlusion of the superior mesenteric artery for 60 minutes leading to I followed or not by 120 minutes of R, according to the group. For IPC, 5 minutes of I prior to 10 minutes of R were established. After this process of I or I-R, the right lung of each animal was adequately prepared for staining with hematoxylin and eosin and subsequent histologic analysis for quantification of inflammatory infiltrate was done. The left lung was frozen and prepared for assessment of oxidative stress by the quantification of thiobarbituric acid-reactivity substances (TBARS). Histologic analysis showed an important inflammatory infiltrate in the I-R + SS (I-R + SS = 4.5), which was significantly (P < .05) reduced by IPC (I-R + IPC = 3.0) or AT (I-R + AT = 3.0). Likewise, the TBARS levels were decreased by both strategies (I-R + SS = 0.63; I R + IPC = 0.23; I-R + AT = 0.38; P < .05). Our results showed that AT and IPC attenuate pulmonary lesions caused by intestinal I and R process. PMID- 25131056 TI - Effect of ischemic preconditioning and postconditioning on liver regeneration in prepubertal rats. AB - BACKGROUND: Liver regeneration has great importance for transplantation, especially in children; however, it has not been studied sufficiently in development animals. Ischemia-reperfusion injury is a problem, and strategies such as ischemic preconditioning and postconditioning are not well defined regarding regeneration. OBJECTIVE: This study sought to evaluate liver regeneration with modulation by ischemic preconditioning and postconditioning in prepubertal rats subjected to total ischemia and reperfusion. METHODS: Thirty five 5-week-old female Wistar rats were divided into groups of 7 animals each: control group (SHAM), 70% hepatectomy (HEP), total ischemia 30 minutes before hepatectomy (IR), ischemic preconditioning 10/10 minutes before ischemia (PRE), and two 30/30-second ischemic postconditioning cycles after ischemia and hepatectomy (POS). All animals were subjected to 24-hour reperfusion. Aspartate aminotransferase and alanine aminotransferase activity were measured to evaluate liver damage, and histological analysis, proliferating cell nuclear antigen (PCNA) and regenerated mass liver were used to evaluate liver regeneration. Statistical analyses were performed using ANOVA and Kruskal-Wallis test. RESULTS: Alanine aminotransferase and aspartate aminotransferase levels were significantly lower in conditioned groups than in the IR group. Regarding mitotic index, IR > control group and HEP (P < .05), PRE and POS were not significantly different from IR, and POS > HEP (P < .05). PCNA analysis showed that IR > HEP (P < .01), PRE < IR (P < .01), and no significant differences were observed between POS and IR groups. No significant differences in regenerated mass liver were observed between conditioned groups and HEP. CONCLUSIONS: Ischemic postconditioning prevented ischemic injury, promoted greater liver regeneration, and should be further investigated as an alternative better than ischemic preconditioning. PMID- 25131057 TI - Effects of immunosuppressive drugs on gastrointestinal transit of rats: effects of tacrolimus, cyclosporine, and prednisone. AB - Triple immunosuppressive therapy after organ transplantation may cause several gastrointestinal disturbances. It is difficult to identify which drug causes more complications, requiring an appropriate animal model. The aim was to compare the gastrointestinal transit in immunosuppressed rats under triple immunosuppressive therapy. Male rats were immunosuppressed by gavage during 14 days with tacrolimus (n = 10), cyclosporine (n = 12), and prednisone (n = 9). Animals received a magnetic pellet before (control) and after treatment that was monitored at predetermined intervals by AC biosusceptometry, a noninvasive and radiation-free technique. The following parameters were measured: creatinine serum, mean time of gastric emptying (MGET), mean time to reach cecum (MCAT), and mean transit time through small bowel (MSBTT). The differences were analyzed by ANOVA (Tukey). Our results showed that MGET of animals treated with prednisone, cyclosporine, and tacrolimus were reduced compared with control subjects (P < .03, P < .009, and P < .002, respectively). There was no difference in MCAT, whereas MSBTT was longer for tacrolimus and prednisone compared with control subjects (P < .004 and P < .004, respectively). Also, prednisone and tacrolimus presented a reduced MGET (P < .05 and P < .01, respectively) compared with cyclosporine. Our data showed a low serum creatinine level and no difference among groups regarding renal function. In summary, cyclosporine has less effect on the gastrointestinal transit; however, all of these drugs should be carefully prescribed to prevent gastrointestinal symptoms and improve quality of life after transplantation. PMID- 25131058 TI - Late biliary obstruction in Wistar rats after intermittent hepatic pedicle clamping. AB - INTRODUCTION: The temporary vascular occlusion of hepatic flow is one of the essential procedures in hepatic surgery. AIM: Evaluate the late liver alterations after intermittent pedicle hepatic clamping (IHPC) in Wistar rats. METHODS: Male Wistar rats (n = 14) with average weight of 281.1 g, were anesthetized with intraperitoneal ketamine 5%. The IHPC group (n = 7) was submitted to U-shaped abdominal incision; the hepatic pedicle was isolated and submitted to IHPC ischemia 4 times, 5 minutes each, followed by reperfusion 4 times, 5 minutes each. The simulated operation group (n = 7) was subjected to anesthesia, laparotomy, and manipulation of the hepatic pedicle. On day 35, after fasting for 12 hours, liver biopsies were collected and blood was tested for liver aminotransferases (aspartate aminotransferase/alanine aminotransferase). RESULTS: All the IHPC group animals had a dilated common bile duct and increased liver enzymes (P < .05 by Mann-Whitney test). Ductular proliferation (100% of cases), porta-porta septa (42.8%), formation of lumps (42.8%), foci of necrosis (14.2%), and bile plugs (14, 2%) were observed only in the IHPC group. CONCLUSION: In rats, IHPC caused morphologic features leading to biliary obstruction. PMID- 25131059 TI - Effect of platelet-rich plasma therapy associated with exercise training in musculoskeletal healing in rats. AB - BACKGROUND: Muscle healing is a time-dependent process associated with an increase in the total amount of local collagen fibers. Platelet-rich plasma therapy (PRPT) associated with exercise may improve this healing process. The aim of this study was to demonstrate the regenerative effect of PRPT in association with exercise training on musculoskeletal healing. METHODS: Male Wistar rats were submitted to an injury in the vastus lateralis muscle and randomly divided into 4 groups (n = 5/group): sedentary sham-operated (SSO); sedentary group submitted to PRPT (SPR); swim-trained (SWT); and swim-trained group submitted to PRPT (SWP). Serum lactate level was used to confirm the training protocol effectiveness to increase aerobic fitness. The collagen fiber concentration was measured by the polarization colors in picrosirius red-stained tissue sections. RESULTS: Lactate levels decreased in both training groups (SWT and SWP; P < .05) after training (SWT: from 6.2 +/- 0.44 to 4.7 +/- 0.22 mmol/L; SWP: from 5.5 +/- 0.99 to 4.0 +/- 0.78 mmol/L). There were less type 1 collagen fibers in SWP group compared with other groups (SSO = 31.8 +/- 10.3, SSP = 32.3 +/- 13.5, SWT = 14.6 +/- 13.4, SWP = 5.7 +/- 4.7, P < .05), while there were more type 3 collagen fibers on SWP (SSO = 68.7 +/- 9.8, SSP = 71.2 +/- 12.2, SWT = 85.4 +/- 13.4, SWP = 94.4 +/- 4.6, P < .05) in the injured region. CONCLUSION: Exercise in association with PRPT enhances the skeletal muscle-healing process. PMID- 25131060 TI - Regeneration of skin tissue promoted by mesenchymal stem cells seeded in nanostructured membrane. AB - BACKGROUND: The mesenchymal stem cell therapy has proven to be an effective option in the treatment of skin injuries. The combination of these cells with nanostructured membranes seems to be the future for tissues recovery. The aim of this project was to use biomolecules of polysaccharides to be incorporated on regenerated cellulose membranes and to prospect the improvement as bioactive wound dressings with mesenchymal stem cells. METHODS: The biocomposites were obtained after defibrillation with the use of never-dried bacterial cellulose to form a pulp, and, after the films were regenerated, in the presence of gellan gum with or without fluconazole. Membrane atomic force microscopy was performed for comparison of their structures. RESULTS: Adipose-derived mesenchymal stem cells were obtained from human adipose tissue liposuction in accordance with Zuk et al. The flow cytometric analysis and induction tests for adipocytes and osteocytes were performed. In vitro assays were performed on different membranes to evaluate the ability of these cells to adhere at 2 hours and proliferate at 7 days; the results were obtained by use of the MTT cell counting technique. In vivo testing allowed us to observe cell migration and participation in wound-healing by fluorescence labeling of the cells with BrdU. The bioactive curative, seeded with cells, was tested in skin burned in a murine model. CONCLUSIONS: The bacterial cellulose with gelan gum membrane incorporated with fluconazole presented the best performance in adhesion and proliferation tests. The cells can be identified in burned host tissue after occurrence of the wound. PMID- 25131061 TI - Rhabdomyolysis as a clinical manifestation of association with ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-alpha in liver-transplanted patients: a case report and literature review. AB - BACKGROUND: Rhabdomyolysis is a syndrome characterized by impaired metabolic integrity of myocytes, causing the release of intracellular constituents into the circulation, and can be a serious side effect of drug intake. CASE REPORT: This report describes a unique case of rabdomyolysis secondary in which ciprofibrate, sirolimus, cyclosporine, and pegylated interferon-alpha in a liver transplant patient was used. A 47-year-old male liver transplant recipient in 2009, who had hepatitis C and incidental hepatocellular carcinoma, underwent immunosuppressive therapy (cyclosporine and sirolimus). The patient is currently in treatment for viral recurrence with pegylated interferon-alpha and ribavirin; he had a history of hypertriglyceridemia treated with ciprofibrate. He had development of severe and generalized myalgia and fever after the eighth application of pegylated interferon-alpha and increasing doses of cyclosporine. Laboratorial tests showed acute renal failure and significant increase in creatine kinase. Rhabdomyolysis secondary to interaction of fibrate-cyclosporine-pegylated interferon-alpha was postulated. CONCLUSIONS: Medical professionals should be aware of possible drug interactions and should monitor patients receiving these drugs. PMID- 25131062 TI - Endovascular management of massive hemobilia as a late complication of percutaneous biliary drainage in a pediatric liver transplant recipient: a case report. AB - Development of biliary strictures after liver transplantation is not uncommon, and minimally invasive procedures are the first-line treatment of choice in most centers. Hemobilia is an infrequent, usually self-limited complication related to the initial biliary access procedure. Massive hemobilia with severe hemodynamic instability is a rare event, particularly as a delayed complication. The difficulty of obtaining surgical access makes management of this condition highly challenging. Endovascular embolization may represent an important treatment option in this setting. PMID- 25131063 TI - Hepatic artery thrombosis in live liver donor transplantation: how to solve--a case report. AB - The decrease in the number of cadaveric donors has proved a limiting factor in the number of liver transplants, leading to the death of many patients on the waiting list. The living donor liver transplantation is an option that allows, in selected cases, increase the number of donors. One of the most serious complications in liver transplantation is hepatic artery thrombosis, in the past considered potentially fatal without urgent re-transplantation. A white male patient, 48 years old, diagnosed with hepatocellular carcinoma in chronic liver failure caused by hepatitis B virus, underwent living donor liver transplantation (right lobe). Doppler echocardiography performed in the immediate postoperative period did not identify arterial flow in the right branch, having been confirmed thrombosis of the right hepatic artery in CT angiography. Urgent re-laparotomy was performed, which consisted of thrombectomy and re-anastomosis of the hepatic artery with segmental splenic artery allograft interposition. The patient started anticoagulation and antiplatelet therapy with acetylsalicylic acid. Serial evaluation with Doppler echocardiography showed hepatic artery patency. At present, the patient is asymptomatic. One of the most devastating complications in liver transplantation, and particularly in living liver donor, is thrombosis of the hepatic artery; thus, early diagnosis and treatment is vital. The rapid intervention for revascularization of the graft avoids irreversible ischemia of the bile ducts and hepatic parenchyma, thus avoiding the need for re transplantation. PMID- 25131065 TI - What defines success in pancreas and islet transplantation-insulin independence or prevention of hypoglycemia? A review. AB - Pancreas transplantation is considered to be the treatment of choice for selected uremic and diabetic patients, and insurance coverage is widely provided. In the USA, islet transplantation is considered to be an experimental procedure that awaits formal results of ongoing phase III trials to justify biologic licensure and transition to standard of care. Pancreas and islet registry analyses focus on different functional endpoints: insulin independence (pancreas transplants) versus avoidance of hypoglycemia (islet transplants). Although the results of islet transplants have significantly improved, the frequent use of multiple donor organs, suboptimal islet yields, and difficulties in monitoring successful engraftment or in diagnosing rejection remain major barriers that need to be overcome. Although pancreas and islet transplantations are frequently considered to be competing procedures, they are actually complementary treatment options for patients with type 1 diabetes mellitus. Because the results of pancreas transplants are superior to those for islet transplants, diabetic patients with a low surgical risk should undergo a pancreas transplantation. Type 1 diabetics with a high surgical risk (eg, serious comorbidities) should undergo an islet transplantation. Only an integrated approach to pancreas and islet transplantation, tailored to the need of the individual patient, will maximize the benefit of a scarce resource. Both procedures, if successful, have in common that they represent the only biologic treatment option to date for type 1 diabetic patients that prevents hypoglycemia long term. PMID- 25131066 TI - Short and long-term outcomes of systemic drainage to IVC: a new technique for pancreas transplantation. AB - Ninety-eight percent of the whole pancreas does not serve the purpose of pancreatic transplantation and it is a major cause of surgical complications. Up to 30% of pancreas transplant recipients experience surgical complications and require reoperation. Graft thrombosis and pancreatitis are the most common complications of pancreas transplantation (PT). Thus, different surgical techniques have been described to overcome the surgical hurdles and reduce surgical complications. In this study, for the first time, we report short- and long-term outcomes of PT with inferior vena cava (IVC) venous drainage. Forty five PTs (22 simultaneous pancreas and kidney [SPK] transplantations and 23 pancreas after kidney [PAK] transplantations) were performed with this technique in our center. Sixty-eight percent of the donors were imported from outside of our area after they were declined by their local transplantation center. Patient and graft survival rates were 100% at 1 year. No graft thrombosis or pancreatitis occurred with this technique. Six patients (13.3%) required reoperation (3 bleeding, 2 anastomotic leak, and 1 small bowel perforation). No patient or graft loss occurred due to surgical complications. We conclude that this technique provides fast and easy dissection of the venous drainage of the PT without the need of complete occlusion of venous outflow. Surgical complication rates were lower with this technique compared with other reported techniques. PMID- 25131067 TI - Simultaneous pancreas-kidney transplantation with duodeno-duodenal anastomosis. AB - Simultaneous pancreas-kidney transplantation (SPKT) is now accepted as the method of choice for patients with insulin-dependent diabetes mellitus (type I) who have end-stage renal disease (ESRD). We believe that retroperitoneal positioning of the donor pancreas with the formation of duodeno-duodenal anastomosis is the most physiologically relevant. Starting in January 2008, the SPKT was chosen as the treatment method of 32 patients with diabetes mellitus. In 15 cases comprising group I (46.9%), the pancreas was placed intra-abdominally (including the formation of the duodeno-jejunal anastomosis). In the remaining 17 patients (53.1%) comprising group II, the pancreas was positioned retroperitoneally (including the formation of the duodeno-duodenal anastomosis). We compared the main parameters of the early postoperative period in these groups. There were no substantial differences between the groups in the prevalence of immunological (13.3% and 11.8%, P = .9), surgical (20% and 23.5%, P = .81), and infectious complications (20% and 5.9%, P = .23). On discharge there were no significant differences in the values of the following between the two groups, respectively: serum creatinine values, 112.7 +/- 31.2 and 104.8 +/- 54.6 MUmol/L, P = .17; glomerular filtration rate, 73.5 +/- 28.6 and 78.7 +/- 24.9 mL/min, P = .55; alpha-amylase, 121.9 +/- 63.6 and 150.1 +/- 72.1 U/L, P = .27; pancreatic amylase, 102 +/- 51.5 and 122.5 +/- 75.4 U/L, P = .6; lipase, 115.4 +/- 67.3 and 96 +/- 65.7 U/L, P = .5; S-peptide, 4.44 +/- 1.9 and 4.02 +/- 2.4 ng/mL, P = .47; HbA1c, 5.45 +/- 0.8% and 5.56 +/- 1.12%, P = .9; and intact insulin, 12.2 +/- 5.4 and 12.9 +/- 8.8 mcIU/mL, P = .95). SPKT remains the best method of medical and social rehabilitation for patients who have diabetes mellitus (type-I) with ESRD. Compared to the classic method, we have seen no significant deviations in either of the following: the qualitative features marking the restoration of function of the two transplanted organs and/or the quality of compensation of carbohydrate metabolism, incidence of rejection, and graft loss. At the same time, retroperitoneal positioning of the pancreas exhibited lower repeat surgery rates. PMID- 25131068 TI - Portal versus systemic venous drainage of the pancreatic graft: the effect on glucose metabolism in pancreas and kidney transplant recipients. AB - Two different methods of graft venous drainage are used in pancreas transplantation: portal (PVD) and systemic (SVD). PVD is considered to be more physiologic due to its similarity to venous outflow of the native pancreas. The aim of our study was to compare glucose metabolism in Type 1 diabetic recipients of kidney and pancreatic grafts with PVD versus SVD by intravenous glucose tolerance test (IVGTT). We examined 28 insulin-independent patients after simultaneous pancreas and kidney transplantation: 14 recipients with PVD of the pancreatic graft and 14 with SVD after a mean post-transplant period of 1 year. All recipients had stable good function of the kidney graft. Fasting glycemia, insulin levels, glycosylated hemoglobin (HbA1c), and standard IVGTT with coefficient of glucose assimilation (KG) calculation were assessed. Insulin sensitivity and production were evaluated using the homeostasis model assessment (homeostasis model assessment of insulin resistance [HOMA-IR], homeostasis model assessment of B-cell function [HOMA-B]). Total C-peptide and insulin secretions were calculated as areas under the curves (AUCs) from the serum levels during the IVGTT. PVD and SVD groups did not differ in age, body mass index (BMI) and duration of post-transplantation period (P >= .05). We did not find any significant difference in fasting glycemia, HbA1c, KG, HOMA-IR, parameters of C peptide level, fasting insulin level, and response during IVGTT. HOMA-B and AUC of insulin level were higher in the SVD group (45.1 +/- 35.1 versus 19.8 +/- 15.5, P =.03 and 1075 +/- 612 versus 1799 +/- 954 mIU/L/60 minutes, P < .03, respectively). In the PVD group, 1 patient had an abnormal response to the glucose stimulus, 8 patients had an impaired glucose tolerance, and 5 patients had a normal glucose tolerance. In the SVD group, an abnormal response was present in none, impaired glucose tolerance in 4, and normal glucose tolerance in 10 recipients. Athough this was not a prospectively randomized trial, we conclude that the change of surgical technique from SVD to PVD did not lead to any substantial change in terms of glucose tolerance. PMID- 25131069 TI - Evaluation of insulin independence using 11C-methionine positron emission tomography after living-donor and brain-dead donor pancreas transplantation. AB - We recently reported that (11)C-methionine positron-emission tomography (PET) is clinically useful for the evaluation of the pancreatic function of the living donor. The objective of this study was to evaluate the postoperative insulin independence in 10 living donor (LD) and 10 brain-dead donor (BD) pancreas transplantations for 20 patients with type I diabetes mellitus by using (11)C methionine PET. After 6 months, PET/computed tomography was performed 30 minutes after (11)C-methionine (370-740 MBq) injection. The uptake in the pancreas was expressed as the standardized uptake value (SUV). Patient survival rates were 100% at 5 years for LD transplantations and at 2 years for BD transplantations. Insulin independence was 60% for LD transplantations at 5 years and 75% for BD transplantations at 2 years. There were no major surgical complications such as vascular thrombosis, intra-abdominal abscess, and graft pancreatitis. The SUVs for LD and BD pancreas transplantations with insulin independence were 7.2 +/- 1.8 and 10.4 +/- 2.3, respectively. The SUVs for LD pancreas transplantations with insulin dependence and BD pancreas transplantations with graft failure were 3.6 +/- 1.1 and 2.9 +/- 1.0, respectively. At 5 years after transplantation, for the LD transplants, the insulin-independent rate was 100% for the graft recipients with an SUV higher than 5, and the median insulin independence duration of the graft recipients with an SUV less than 5 was 7 months (P < .01). The (11)C-methionine PET may be a potent modality to predict long-term insulin independence and the avoidance of pancreas graft failure. PMID- 25131070 TI - A novel screening test for detecting graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography with sonazoid. AB - Pancreatic graft thrombosis is the primary cause of nonimmunologic graft loss, with an incidence ranging from 5% to 15%. Therefore, developing a screening test to detect graft thrombosis after pancreatic transplantation is important. We created a screening test to assess graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography (CEUS) with Sonazoid in addition to Doppler ultrasonography. A total of seven patients were examined using CEUS after undergoing pancreatic transplantation. All patients were observed to have a clear blood flow from the horizontal region to the peripheral region of the splenic vein in the pancreatic graft, and only one of the seven patients exhibited a blood flow in the horizontal portion of the splenic vein on Doppler ultrasonography performed immediately after pancreatic transplantation. Results from CEUS with Sonazoid showed the blood flow in the splenic vein and parenchyma of the pancreatic graft in detail, despite the slow and lateral blood flow in the splenic vein of the pancreatic graft immediately after transplantation. PMID- 25131071 TI - Long-term outcomes of pancreas after kidney transplantation in small centers: is it justified? AB - BACKGROUND: Currently, the long-term advantages of having a pancreas transplantation (PT) are debated, particularly in patients receiving pancreas after kidney (PAK) allografts. The United Network for Organ Sharing (UNOS) requires that a transplant center perform a minimum number of PT per year to remain an active PT center. The long-term outcomes and challenges of PAK in small pancreas transplant centers are not well studied. METHODS: In this retrospective analysis, we report short- and long-term outcomes in a small center performing 2 9 PT annually. RESULTS: Forty-eight PT (25 simultaneous pancreas and kidney transplantation [SPK], 23 PAK) were performed in our center. Donor and recipient demographics were similar in both groups. All suitable local donors were used for SPK. All organs for PAK transplantation were imported from other UNOS regions. Mean follow-up was 61 +/- 46 and 74 +/- 46 months for SPK and PAK, respectively. Patient and graft survival rates were similar in SPK and PAK groups and better than the reported national average. Four patients (11%) died (1 due to trauma, 1 brain lymphoma, 1 ruptured aneurysm; and 1 unknown cause). Two patients (4%; 1 SPK, 1 PAK) lost their grafts because of thrombosis on postoperative days 3 and 5 in 2002. No graft thrombosis occurred since 2002. Seven patients (15%) required reoperation (4 for bleeding, 2 anastomotic leaks, 1 small bowel perforation). Two patients (4%) developed post-transplantation lymphoproliferative disease. Five patients (11%) experienced cytomegalovirus antigenemia which responded well to antiviral therapy. CONCLUSIONS: Compared with outcomes for diabetic patients on dialysis, current SPK and PAK short- and long-term results are favorable even in a small PT center. Therefore, unless there is a contraindication, PT should be offered to all type 1 diabetic patients with end-stage renal disease at the time of kidney transplantation or afterward. PMID- 25131072 TI - Similar results with solitary pancreas transplantation compared with simultaneous pancreas-kidney transplantation in the new millennium. AB - INTRODUCTION: The purpose of this study was to analyze our single-center outcomes according to pancreas transplant (PT) category in the new millennium by using standardized management protocols. PATIENTS AND METHODS: We retrospectively studied 202 consecutive PTs (179 with portal-enteric drainage) in 192 patients; all received either rabbit antithymocyte globulin or alemtuzumab induction in combination with tacrolimus, mycophenolate mofetil, and tapered corticosteroids or early steroid withdrawal. Unlike simultaneous pancreas/kidney (SPK) transplant, solitary PT (SPT) recipients were managed with routine perioperative anticoagulation and surveillance pancreas biopsies. RESULTS: From November 2001 to March 2013, we performed 162 SPK transplants, 35 pancreas after kidney transplants, and 5 pancreas-alone transplants (40 SPTs). Demographic characteristics were mostly comparable; however, the SPT group had younger donors, shorter waiting time, fewer HLA mismatches, and fewer African-American recipients but more retransplants (all, P < .05). With a mean follow-up of 5.5 versus 7.5 years, overall patient (86.4% SPK vs 86.8% SPT), kidney graft (74% SPK vs 80% SPT), and pancreas graft (both 65%) survival rates were comparable. Although mortality rates were similar, mortality patterns differed because no SPT recipients died early, whereas the 1-, 3-, and 5-year mortality rates after SPK transplant were 4%, 9% and 12%, respectively (P < .05). The most common causes of pancreas graft loss were death with functioning grafts in SPK recipients and acute/chronic rejection in SPT recipients. Rates of early thrombosis were 8.6% in SPK patients and 5% in SPT patients. Cumulative clinical acute rejection rates were similar between groups (SPK 29% vs SPT 27.5%; P = NS). CONCLUSIONS: In the setting of depleting antibody induction and tacrolimus-based therapy, HLA matching, careful donor and recipient selection, portal-enteric drainage, selective perioperative anticoagulation, and surveillance SPT biopsy monitoring, similar medium-term outcomes can be achieved in SPK transplants and SPTs in the new millennium. PMID- 25131073 TI - 5-year results of a prospective, randomized, single-center study of alemtuzumab compared with rabbit antithymocyte globulin induction in simultaneous kidney pancreas transplantation. AB - INTRODUCTION: The study purpose was to analyze 5-year outcomes in a prospective, randomized trial of alemtuzumab (ALEM) versus rabbit antithymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT). PATIENTS AND METHODS: From February 2005 through October 2008, a total of 46 SKPTs (45 portal-enteric drainage) were prospectively randomized to receive either single dose ALEM (30 mg intraoperatively) or multiple-dose rATG antibody induction (starting intraoperatively, minimum of 3 doses administered) with tacrolimus/mycophenolate and/or steroids. RESULTS: Of 222 kidney transplant patients enrolled in the study, 46 received SKPTs; 28 (61%) received ALEM and 18 (39%) received rATG induction. Follow-up ranged from 54 to 98 months (mean, 69 months). There were no significant differences between the 2 groups in 5-year patient (82% ALEM vs 89% rATG), kidney graft (79% ALEM vs 72% rATG), or pancreas graft (64% ALEM vs 56% rATG) survival rates. Death-censored kidney (90% ALEM vs 75% rATG) and pancreas (71% ALEM vs 56% rATG) graft survival rates were likewise comparable (both, P = NS). Acute rejection (21% ALEM vs 44% rATG; P = .11) and major infection (39% ALEM vs 67% rATG; P = .13) rates were slightly lower in the ALEM group; cytomegalovirus infections were significantly lower (0% ALEM vs 17% rATG; P = .05). The incidence of late acute rejection was low in both groups. There were no differences in early pancreas thromboses (3.6% ALEM vs 11% rATG), postoperative bleeding (11% ALEM vs 0% rATG), other surgical complications, or readmissions between groups. In patients with functioning grafts, 5-year mean serum creatinine (1.4 ALEM vs 1.6 mg/dL rATG), calculated abbreviated Modification of Diet in Renal Disease glomerular filtration rate (55 ALEM vs 52 mL/min/1.73 m(2) rATG), glycosylated hemoglobin (both 5.4%), and C-peptide (2.2 ALEM vs 2.3 ng/mL rATG) levels were similar. CONCLUSIONS: Single-dose ALEM and multiple dose rATG induction provided similar medium-term patient, kidney, and pancreas graft function and survival rates. ALEM induction may be associated with less acute rejection and major infection over the long term. PMID- 25131074 TI - Excellent outcomes can be achieved in young pancreas transplant alone recipients by addition of sirolimus to maintenance immunosuppression regimen. AB - BACKGROUND: Pancreas transplant alone (PTA) has evolved into a viable treatment option for nonuremic patients with labile diabetes mellitus. Historically, PTA outcomes were inferior to simultaneous pancreas-kidney transplant outcomes, because of the higher rate of graft loss due to rejection in PTA recipients. But with advances in immunosuppression, PTA outcomes have improved significantly- except in young PTA recipients. The more potent immune system in young recipients appears to play a key role. In this study, our objective was to investigate outcomes of PTA, by recipient age, with the use of different immunosuppressive maintenance regimens. METHODS: Using information from the International Pancreas Transplant Registry and from the United Network for Organ Sharing, we analyzed outcomes of 393 technically successful enteric-drained transplants in the PTA category that were performed from January 2003 through December 2012. All PTA recipients underwent induction immunosuppression with thymoglobulin and pulse steroids and were then maintained on long-term low-dose prednisone. Excluded from our study group were patients who experienced surgical graft loss. We divided the 393 recipients into 2 age groups: <42 years (187 patients) versus >=42 years (206 patients). For both the younger group and the older group, we compared 2 maintenance immunosuppressive regimens: (1) tacrolimus (Tac) and mycophenolate mofetil (MMF) versus (2) Tac/MMF and sirolimus (Srl). We refer to immunosuppression with Tac and MMF as the non-Srl regimen. RESULTS: The overall 3 year graft survival rate, across both age groups, was significantly better with the Srl regimen (P = .03). Regardless of the immunosuppressive regimen used, outcomes were significantly better in the older group than in the younger group (P = .05). In the older group, with both regimens, outcomes were similar (P = .55). But in the younger group, outcomes with the Srl regimen were significantly better (P = .009) than with the non-Srl regimen and, in fact, were similar to outcomes in the older group. CONCLUSIONS: Our study shows that adding Srl to the standard maintenance immunosuppressive regimen of Tac and MMF provides the best outcomes in young PTA recipients, the most immunologically robust and therefore the most immunologically challenging age group. To achieve excellent outcomes, more potent immunosuppression is required in this cohort. We think that PTA should be offered to young patients with labile diabetes before secondary complications develop. PMID- 25131075 TI - Declining numbers of pancreas transplantations but significant improvements in outcome. AB - In the United States, over the past 8 years, the number of pancreas transplantations has steadily declined. This decline comes as a surprise, because patient and graft outcomes have substantially improved during the same period of time. Patient survival rates at 1 year in all 3 recipient categories are >96%; graft survival rates are 82%-89%. Changes in immunosuppressive therapy have had a positive impact on outcome, as have better pancreas donor and recipient selection criteria and refined post-transplantation patient care. Although different factors may have contributed to the declining pancreas transplantation numbers, a more effective process of publicly promoting and widely communicating the improved results of pancreas transplantation is warranted. PMID- 25131076 TI - High urine amylase level and the risk of enteric conversion in solitary pancreas transplant recipients. AB - INTRODUCTION: Compared with enteric drainage, bladder-drained solitary pancreas transplants can be monitored for rejection by measuring urine amylase levels. However, bladder drainage is associated with a higher risk of infection and metabolic complications, necessitating enteric conversion in about one third of patients. We hypothesized that hypersecreting pancreata with high urine amylase levels have a higher propensity for enteric conversion from an antecedent elevated enzymatic effect on the urinary tract and increased fluid losses. PATIENTS AND METHODS: We analyzed the risk for enteric conversion in 312 bladder drained solitary pancreas transplant recipients. Urine amylase levels at 30 days were used to identify those at risk for enteric conversion. Time-to-event analysis was used to evaluate the risk of enteric conversion at 10 years, adjusting for urine amylase level and other confounding factors. Confounding risk factors statistically related to enteric conversion were incorporated into the multivariable analysis by using Cox proportional hazards regression at 3 years' posttransplant. RESULTS: During the median follow-up of 184.6 months, 31% of recipients underwent duct conversion. A majority of recipients (84.5%) who required duct conversion were primary transplants. The 30-day median urine amylase level was 1749 IU/h (quartile 1, <777 IU/h; quartile 3, >=3272 IU/h). Using receiver operating characteristic analysis, it was determined that urine amylase levels >3272 IU/h had the greatest specificity for predicting risk of enteric conversion. In the multivariate analysis, high urine amylase levels increased the risk of enteric conversion only in repeated pancreas transplants. CONCLUSIONS: Primary transplants are more likely to undergo enteric conversion than retransplants. High urine amylase levels increase the risk of enteric conversion in retransplants only, and therefore this enzyme alone cannot serve as the sole predictor for conversion in primary transplants. Other factors, such as fluid and bicarbonate losses, increased bladder pressure, and a pre-existing lower urinary tract pathologic condition may be also responsible for the development of complications; these factors warrant additional study. PMID- 25131077 TI - The influence of collagen III expression on the efficiency of cell isolation with the use of collagenase H. AB - OBJECTIVE: We previously demonstrated that collagenase H (ColH) plays a crucial role in rat islet isolation, whereas collagenase G (ColG) plays only a supporting role. We also showed that collagen III appears to be one of the key targets of ColH based on a mass spectrometry analysis. In the present study, we investigated whether our novel findings in an islet isolation model are universally applicable for other types of cell isolation, such as a hepatocyte isolation, with the use of enzyme blends of recombinant collagenases. METHODS: As the first step, the expression of one of the main matrix components, collagen III, on rat pancreatic and hepatic tissues was assessed with the use of immunohistochemical staining. ColG and ColH were expressed in recombinant E. coli carrying expression plasmids for each collagenase. Then the efficiency of the collagenase subtype on rat hepatocyte isolation was evaluated in terms of cell yield with the use of thermolysin combined with either ColG or ColH (n = 3, respectively). RESULTS: The expression of collagen III on rat hepatic tissues was dramatically lower than that of rat pancreatic tissues. In the rat hepatocyte isolation, a substantial amount of hepatocytes (0.81 +/- 0.11 * 10(6)) were obtained in the ColG group, whereas almost no hepatocytes were retrieved in the ColH group, indicating that the influence of the collagenase subtypes in rat hepatocyte isolation are completely opposite to that observed in rat islet isolation. CONCLUSIONS: Considering that the expression of collagen III on hepatic tissues was relatively low and that almost no hepatocytes were retrieved when ColH and thermolysin were used, the present study supports our novel finding that collagen III appears to be one of the key targets of ColH in hepatocyte isolation. Therefore, the semiquantification of collagen III on the target tissues not only may positively contribute to efficient islet isolation, but also may affect other types of cell isolation by optimizing the ColH amount. PMID- 25131078 TI - Pretreatment of donor pigs with a diet rich in soybean oil increases the yield of isolated islets. AB - INTRODUCTION: The pig is considered the donor species of choice for islet xenotransplantation. However, isolation of porcine islets is difficult, particularly from young pigs. Early life exposure to a high-fat diet (HFD) reportedly encourages islet beta-cell expansion in neonatal rodents and improves islet viability in culture from pretreated weanling pigs. In this study, we examined the influence of young donor pretreatment with a soybean oil-enriched HFD on porcine islet mass and yield after islet isolation. MATERIALS AND METHODS: Postweaning and between days 70 and 250, pigs were fed either a standard diet (control group; n = 5) or an HFD (experimental group; n = 6). Biochemical blood parameters and acute C-peptide response to intravenous glucose were monitored before pancreas procurement. The study was blinded to objectively evaluate the influence of treated diet. After procurement, pancreas biopsy samples were taken from control and pretreated donor pigs to assess islet number by using a dithizone scoring method and histologic islet area fraction determination. Control and HFD donor pig islets were isolated by using our standard isolation protocol to determine islet yield. Islet isolation characteristics and islet quality were assessed in both groups, and the results were compared. RESULTS: There were no significant differences in the donor characteristics (age, body weight, glucose disposal rate, acute C-peptide response to intravenous glucose, cholesterol, and aspartate aminotransferase) except fasting blood glucose level between the control and treatment groups (84 +/- 6 vs 99 +/- 12 mg/dL; P = .0317). The stimulated insulin and C-peptide levels between groups were similar. However, the dithizone score was slightly higher in the treatment group compared with the control group (95.4 +/- 38.5 vs 62.6 +/- 23.9; P = .1208). Digestion time, digested pancreas weight, pellet volume, and the fragility index were similar in both groups. However, the average islet count (islet equivalent number/g pancreas) at the digest level was significantly higher in the HFD group than in the control group (1578 +/- 994 vs 738 +/- 202; P = .0344). The functional viability of 2- and 7 day-cultured islets, as assessed by using oxygen consumption rate corrected for DNA, was similar in both groups. CONCLUSIONS: Pretreatment of pigs with HFD enriched with soybean oil could potentially be used to improve the islet mass in donor pigs. Further studies are needed to confirm and optimize the use of HFD for the purpose of increasing islet yield from young donor pigs. PMID- 25131079 TI - Effects of all-trans retinoid acid and exendin-4 on islet transplantation in NOD mice. AB - Type 1 diabetes usually develops due to autoimmune destruction of beta-cells in the pancreas. It has been shown that all-trans retinoid acid (ATRA), a potent derivative of vitamin A, hinders the development of autoimmune diabetes by inducing immune tolerance status. In addition, exendin-4, a glucagon-like peptide 1 receptor agonist, stimulates growth and differentiation of beta-cells and exerts anti-apoptotic effect on beta-cells. Thus, we hypothesized that the ATRA and exendin-4 therapy may improve the outcome of islet transplantation in non obese diabetic (NOD) mice. After the onset of diabetes, each NOD mouse was transplanted with 300 or 600 islets isolated from NOD/severe combined immunodeficient (SCID) mice with or without treatment of ATRA (0.5 mg intraperitoneally every other day) and/or exendin-4 (3 MUg/kg subcutaneously twice daily) for 6 weeks. After 300 or 600 NOD/SCID islet transplantation without any other treatment, all NOD recipients remained diabetic. However, the lowest blood glucose level in mice transplanted with 600 but not 300 islets was significantly lower than those without islet transplantation (P < .05), although their survival time was comparable. Among recipients treated with ATRA, exendin 4, ATRA and exendin-4, and without treatment, their lowest blood glucose levels and survival time were not different. However, one recipient treated with ATRA survived for 223 days with intermittent hyperglycemia and the other who was treated with ATRA and exendin-4 achieved normoglycemia. In conclusion, islet transplantation lowered blood glucose levels in diabetic NOD mice. With a few exceptions, treatment with ATRA and exendin-4 alone or in combination in islet recipients could not reverse diabetes or prolong survival. PMID- 25131080 TI - Islet preparation purity is overestimated, and less pure fractions have lower post-culture viability before clinical allotransplantation. AB - BACKGROUND: Replacement of beta-cells with the use of isolated islet allotransplantation (IT) is an emerging therapy for type 1 diabetics with hypoglycemia unawareness. The current standard protocol calls for a 36-72-hour culture period before IT. We examined 13 clinical islet preparations with >=2 purity fractions to determine the effect of culture on viability. METHODS: After standard islet isolation and purification, pure islet fractions were placed at 37 degrees C with 5% CO2 for 12-24 hours and subsequently moved to 22 degrees C, whereas less pure fractions were cultured at 22 degrees C for the entire duration. Culture density was targeted at a range of 100-200 islet equivalents (IEQ)/cm(2) adjusted for purity. Islets were assessed for purity (dithizone staining), quantity (pellet volume and DNA), and viability (oxygen consumption rate normalized to DNA content [OCR/DNA] and membrane integrity). RESULTS: Results indicated that purity was overestimated, especially in less pure fractions. This was evidenced by significantly larger observed pellet sizes than expected and tissue amount as quantified with the use of a dsDNA assay when available. Less pure fractions showed significantly lower OCR/DNA and membrane integrity compared with pure. The difference in viability between the 2 purity fractions may be due to a variety of reasons, including hypoxia, nutrient deficiency, toxic metabolite accumulation, and/or proteolytic enzymes released by acinar tissue impurities that are not neutralized by human serum albumin in the culture media. CONCLUSIONS: Current clinical islet culture protocols should be examined further, especially for less pure fractions, to ensure the maintenance of viability before transplantation. Even though relatively small, the difference in viability is important because the amount of dead or dying tissue introduced into recipients may be dramatically increased, especially with less pure preparations. PMID- 25131081 TI - Assessment of human islet grafts in frozen sections of CD-1 athymic nu/nu mouse liver for molecular analysis. AB - BACKGROUND: Post-transplantation islet graft monitoring is hampered by a lack of efficient methods to locate and analyze islets in situ. We evaluated histologic methods to rapidly locate islets within the liver parenchyma post transplantation, using several staining strategies, prior to analysis using laser capture microdissection. METHODS: Human islets were isolated (n = 8) from brain dead, multiorgan donor pancreases at the McGill University Health Centre Islet Transplant Laboratory. Mean yield was 247,609 +/- 195,272 IE and 3172 +/- 1645 IE/g (purity and viability, respectively, 84.5 +/- 8.6% and 95 +/- 5% average; mean +/- SD). Diabetic athymic CD-1 nu/nu mice (streptozotocin intraperitoneal injection, 200 mg/kg) were maintained with sustained release insulin pellets until a suitable islet preparation was available for transplant. Intraportal islet transplantation of 2000 IE/mouse was performed via the ileocecal vein, as previously described. Frozen sections of liver containing human islets were prepared from specimens collected on days 0, 4, and 30 post-transplant. Every twentieth slide from serial sectioned liver was stained using a rapid protocol to determine if islets were present. Sections were fixed and stained for 5 minutes with either an anti-human insulin fluorescein isothiocyanate (FITC)-conjugated primary antibody (Ins-FITC), Newport Green (NG), or diphenylthiocarbazone (dithizone, DZ). RESULTS: Islets were readily localized using each technique, mostly toward the liver periphery. However, DZ had a faint appearance in 10-MUm thick sections and was best utilized to locate sections containing islets during sectioning. CONCLUSION: Ins-FITC, NG, and DZ are all good candidates for a rapid islet staining protocol to evaluate human islet grafts in situ, with DZ being best for sectioning and Ins-FITC and NG being equal in locating islets during processing for laser capture microdissection. PMID- 25131082 TI - Metabolic profile of pancreatic acinar and islet tissue in culture. AB - BACKGROUND: The amount and condition of exocrine impurities may affect the quality of islet preparations, especially during culture. In this study, the objective was to determine the oxygen demand and viability of islet and acinar tissue post-isolation and whether they change disproportionately while in culture. METHOD: We compared the oxygen consumption rate (OCR) normalized to DNA (OCR/DNA, a measure of fractional viability in units of nmol/min/mg DNA), and the percent change in OCR and DNA recoveries between adult porcine islet and acinar tissue from the same preparation (paired) over 6-9 days of standard culture. Paired comparisons were done to quantify differences in OCR/DNA between islet and acinar tissue from the same preparation, at specified time points during culture. RESULTS: The mean (+/-SE) OCR/DNA was 74.0 +/- 11.7 units higher for acinar (vs islet) tissue on the day of isolation (n = 16, P < .0001), but 25.7 +/- 9.4 units lower after 1 day (n = 8, P = .03), 56.6 +/- 11.5 units lower after 2 days (n = 12, P = .0004), and 65.9 +/- 28.7 units lower after 8 days (n = 4, P = .2) in culture. DNA and OCR recoveries decreased at different rates for acinar versus islet tissue over 6-9 days in culture (n = 6). DNA recovery decreased to 24 +/- 7% for acinar and 75 +/- 8% for islets (P = .002). Similarly, OCR recovery decreased to 16 +/- 3% for acinar and remained virtually constant for islets (P = .005). CONCLUSION: Differences in the metabolic profile of acinar and islet tissue should be considered when culturing impure islet preparations. OCR-based measurements may help optimize pre-islet transplantation culture protocols. PMID- 25131083 TI - Effect of mesenchymal stem cells on the vascularization of the artificial site for islet transplantation in rats. AB - An adequate vascularization of the artificially created cavity is crucial for subsequent transplantation of isolated pancreatic islets. In a reported study, dynamic contrast-enhanced magnetic resonance imaging was used to assess the effect of mesenchymal stem cells on neoangiogenesis within connective tissue surrounding an implantable biocompatible device. The signal increase detected after injection of magnetic resonance contrast agent in each target region was considered to be an effect of contrast agent, which was related to the blood supply. To minimize the influence of variability in contrast agent application, all outcomes measured in the implanted devices were normalized to the signal intensity of kidney tissue. When supported by mesenchymal stem cells, the mean signal increase intra-abdominally was 42%, 41%, and 64% and within subcutaneously implanted devices was 23%, 54%, and 52% of that measured in kidney. PMID- 25131085 TI - Donor height in combination with islet donor score improves pancreas donor selection for pancreatic islet isolation and transplantation. AB - To maximize the islet isolation yield for successful islet transplantation, the key task has been to identify an ideal pancreas donor. Since implementation of the islet donor score in donor selection, we have consistently obtained higher islet yields and transplantation rates. In this study, we tested whether assessing donor height as an independent variable in combination with the donor score could improve the pancreas donor selection. Donor and islet isolation information (n = 22) were collected and studied between 2011 and 2012. Pearson correlation analysis was used in statistical analysis. Donor height as an independent variable was significantly correlated to the weight of the pancreas, pre-Islet Equivalents (pre-IEQ), post-IEQ, and IDS (P < .05). When donor with height of 179 cm +/- 3 was selected in combination with IDS > 80, the clinical islet transplantation rate reached 80%. PMID- 25131084 TI - Improved coating of pancreatic islets with regulatory T cells to create local immunosuppression by using the biotin-polyethylene glycol-succinimidyl valeric acid ester molecule. AB - BACKGROUND: We showed that T regulatory (Treg) cells can be attached to the surface of pancreatic islets providing local immunoprotection. Further optimization of the method can improve coating efficiency, which may prolong graft survival. In this study, we compared the effectiveness of two different molecules used for binding of the Tregs to the surface of pancreatic islets. Our aim was to increase the number of Treg cells attached to islets without compromising islets viability and function. METHODS: The cell surface of human Treg cells and pancreatic islets was modified using biotin-polyethylene glycol-N hydroxylsuccinimide (biotin-PEG-NHS) or biotin-PEG-succinimidyl valeric acid ester (biotin-PEG-SVA). Then, islets were incubated with streptavidin as islet/Treg cells binding molecule. Treg cells were stained with CellTracker CM DiL dye and visualized using a Laser Scanning Confocal Microscope. The number of Treg cells attached per islets surface area was analyzed by Imaris software. The effect of coating on islet functionality was determined using the glucose stimulated insulin response (GSIR) assay. RESULTS: The coating procedure with biotin-PEG-SVA allowed for attaching 40% more Treg cells per 1 MUm(2) of islet surface. Although viability was comparable, function of the islets after coating using the biotin-PEG-SVA molecule was better preserved than with NHS molecule. GSIR was 62% higher for islets coated with biotin-PEG-SVA compared to biotin-PEG NHS. CONCLUSION: Coating of islets with Treg cells using biotin-PEG-SVA improves effectiveness with better preservation of the islet function. Improvement of the method of coating pancreatic islets with Treg cells could further facilitate the effectiveness of this novel immunoprotective approach and translation into clinical settings. PMID- 25131086 TI - Impact of hypothermic preservation on tissue yield and viability in pig pancreata. AB - INTRODUCTION: Chronic shortage of quality human cadaveric pancreata limits islet transplantation. Porcine islet xenotransplantation is being explored to increase the donor pool. For clinical-ready islets, centralized animal husbandry, Current Good Manufacturing Practice-regulated processing facilities, and organ transportation support are required. Amount of cold ischemia time (CIT) before isolation significantly affects transplantation. The goal of this study was to determine the maximum safe CIT of whole pancreata before islet isolation. MATERIALS AND METHODS: Pancreata were rapidly removed from Yorkshire pigs (age, 14-22 days) and stored in modified University of Wisconsin solution or in EuroCollins solution at 4( degrees )C. Pancreata were processed with <1 hour CIT (control) or stored for 4 or 12 hours before isolation. Islet yield and percent purity and viability were determined after 7 days of in vitro tissue culture and maturation. Samples from nonprocessed pancreata were collected and snap-frozen in liquid nitrogen at 0, 3, 6, 9, 12, 15, and 24 hours of preservation, then analyzed for adenosine diphosphate/adenosine triphosphate ratio as a measure of tissue energetics. RESULTS: Up to 12 hours in cold storage had no significant impact on overall islet yield after 7 days of in vitro culture compared with controls; islet yield at the end of the maturation process was 28,700 +/- 500 islet equivalents per pancreas (mean +/- SEM control yield, 30,300 +/- 900 islet equivalents per pancreas); islet purity was 75 +/- 5% compared with 74 +/- 5% in controls. Islet viability was significantly reduced at 12 hours compared with controls (80 +/- 6% vs 96 +/- 5%; P < .05). The tissue adenosine diphosphate/adenosine triphosphate ratio was maintained within the first 6 hours (1.6 +/- 0.1 to 1.8 +/- 0.2; P = NS) but was markedly increased during the 24 hour study (3.3 +/- 0.1 at 24 hours), indicating a progressive loss of adenosine triphosphate tissue stores. CONCLUSIONS: Young pig pancreata can be hypothermically stored for up to 12 hours without affecting islet yield and purity; however, islet viability is reduced. These data highlight the need for uniform shipping parameters to standardize islet quality, ideally with CIT <6 hours. PMID- 25131087 TI - Results of open and robot-assisted pancreatectomies with autologous islet transplantations: treating chronic pancreatitis and preventing surgically induced diabetes. AB - For patients with chronic pancreatitis (CP), standard surgical procedures (eg, partial or total resections, drainage procedures) are inadequate treatment options, because they do not confer pain relief and they leave patients prone to brittle diabetes and hypoglycemia. The combination of total pancreatectomy and islet autotransplantation (TP-IAT), however, can create insulin-independent and pain-free states. At our center, from August 2009 through August 2013, 61 patients with CP underwent either open or robot-assisted TP-IAT. The 30-day mortality rate was 0%. The transplanted islet equivalents per body weight ranged from 10,000 to 17,770. In all, 19% of the patients became insulin independent (after a range of 1-24 months); 27% of patients required <10 units of insulin. Moreover, at 12 months after surgery, 71% of the patients were pain free and no longer required analgesics. Our metabolic outcomes could have been even better if most patients had been referred at an earlier disease stage; instead, ~80% had already undergone surgical procedures, and 91% had abnormal results on preoperative continuous glucose monitoring tests. Only if patients with CP are referred early for a TP-IAT-rather than being subjected to additional inadequate endoscopic and surgical procedures-can insulin-independent and pain-free states be accomplished in most. PMID- 25131088 TI - Long-term outcomes of clinical transplantation of pancreatic islets with uncontrolled donors after cardiac death: a multicenter experience in Japan. AB - BACKGROUND: Pancreatic islet transplantation has emerged as an effective treatment for type 1 diabetes mellitus, but its use is limited due to an insufficient supply of cadaveric pancreata. In Japan, uncontrolled donors after cardiac death (DCD) are not deemed to be suitable for whole-organ pancreatic transplantation, and can provide a source of pancreas for islet transplantation. However, the long-term outcomes and utility of uncontrolled DCD in the clinical setting remain controversial. Here, we summarize the long-term outcomes of islet transplantation employing uncontrolled DCD as reported to the Japan Islet Transplantation Registry. METHODS: Sixty-four isolations and 34 transplantations of pancreatic islets were conducted in 18 subjects with type 1 diabetes mellitus under the cover of immunosuppression with basiliximab, sirolimus, and tacrolimus. All donors were uncontrolled DCD at the time of harvesting. The mean follow-up time was 76 months. RESULTS: Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survivals (defined as a C-peptide level >=0.3 ng/mL) were 72.2%, 44.4%, and 22.2% at 1, 2, and 5 years, respectively, whereas the corresponding graft survivals after multiple infusions were 90.0%, 70.0%, and 30.0%, respectively. Three of these recipients achieved insulin independence in 14, 79, and 215 days. HbA1c levels and the requirement of exogenous insulin were improved before loss of graft function. All recipients became free of severe hypoglycemia unawareness, however, at least 5 of 14 patients who had graft failure experienced recurrence of severe hypoglycemia after the loss of graft function. CONCLUSIONS: Islet transplantation from DCD can relieve glucose instability and problems with hypoglycemia when the graft is functioning. However, islets from uncontrolled DCD may be associated with reduced long-term graft survival. Further improvements in the clinical outcome by modification of islet isolation/transplantation protocols are necessary to establish islet transplantation using DCD. PMID- 25131089 TI - Islet oxygen consumption rate dose predicts insulin independence for first clinical islet allotransplants. AB - BACKGROUND: Human islet allotransplantation for the treatment of type 1 diabetes is in phase III clinical trials in the U.S. and is the standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose-stimulated insulin release, and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following 1 transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. METHOD: In this article we report on the assessment of clinical islet allograft preparations using OCR dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. RESULTS: OCR dose was most predictive of CTO. IE dose was also highly predictive, while glucoses stimulated insulin release and membrane integrity stains were not. CONCLUSION: OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical human islet allotransplantation. PMID- 25131090 TI - Human islet viability and function is maintained during high-density shipment in silicone rubber membrane vessels. AB - BACKGROUND: The shipment of human islets (IE) from processing centers to distant laboratories is beneficial for both research and clinical applications. The maintenance of islet viability and function in transit is critically important. Gas-permeable silicone rubber membrane (SRM) vessels reduce the risk of hypoxia induced death or dysfunction during high-density islet culture or shipment. SRM vessels may offer additional advantages: they are cost-effective (fewer flasks, less labor needed), safer (lower contamination risk), and simpler (culture vessel can also be used for shipment). METHOD: IE were isolated from two manufacturing centers and shipped in 10-cm(2) surface area SRM vessels in temperature- and pressure-controlled containers to a distant center after at least 2 days of culture (n = 6). Three conditions were examined: low density (LD), high density (HD), and a microcentrifuge tube negative control (NC). LD was designed to mimic the standard culture density for IE preparations (200 IE/cm(2)), while HD was designed to have a 20-fold higher tissue density, which would enable the culture of an entire human isolation in 1-3 vessels. Upon receipt, islets were assessed for viability (measured by oxygen consumption rate normalized to DNA content [OCR/DNA)]), quantity (measured by DNA), and, when possible, potency and function (measured by dynamic glucose-stimulated insulin secretion measurements and transplants in immunodeficient B6 Rag(+/-) mice). Postshipment OCR/DNA was not reduced in HD vs LD and was substantially reduced in the NC condition. HD islets exhibited normal function postshipment. Based on the data, we conclude that entire islet isolations (up to 400,000 IE) may be shipped using a single, larger SRM vessel with no negative effect on viability and ex vivo and in vivo function. PMID- 25131091 TI - Clinical porcine islet xenotransplantation under comprehensive regulation. AB - BACKGROUND: Xenotransplantation with porcine islets is a promising approach to overcome the shortage of human donors. This is the first report of phase 1/2a xenotransplantation study of encapsulated neonatal porcine islets under the current framework of regulations for xenotransplantation in New Zealand. METHODS: Newborn piglets were anesthetized and bled, and the pancreata were removed with the use of sterile technique and processed. Encapsulated neonatal porcine islets were implanted with the use of laparoscopy into the peritoneal cavity of 14 patients with unstable type 1 diabetes without any immunosuppressive drugs. The patients received encapsulated islets of 5,000 (n = 4; group 1), 10,000 (n = 4; group 2), 15,000 (n = 4; group 3), or 20,000 (n = 2; group 4) islet equivalents per kg body weight. Outcome was determined from adverse event reports, HbA1c, total daily insulin dose, and frequency of unaware hypoglycemic events. To assess graft function, transplant estimated function (TEF) scores were calculated. Sufficient or marginal numbers of encapsulated neonatal porcine islets were transplanted into streptozotocin-induced diabetic B6 mice as an in vivo functional assay. RESULTS: There were 4 serious adverse events, of which 3 were considered to be possibly related to the procedure. Tests for porcine endogenous retrovirus DNA and RNA were all negative. The numbers of unaware hypoglycemia events were reduced after transplantation in all groups. Four of 14 patients attained HbA1c <7% compared with 1 at baseline. The average TEF scores were 0.17, 0.02, -0.01, and 0.08 in groups 1, 2, 3, and 4 respectively. The in vivo study demonstrated that a sufficient number of the transplanted group reversed diabetes with positive porcine C-peptide. CONCLUSIONS: Transplantation of encapsulated neonatal porcine islets was safe and was followed by a reduction in unaware hypoglycemia events in unstable type 1 diabetic patients. The mouse in vivo assessment data demonstrated certain graft function. PMID- 25131092 TI - Pancreatic islet autotransplantation after completion pancreatectomy for pancreatic fistula after hemipancreatoduodenectomy for carcinoma. AB - OBJECTIVE: Pancreatic islet autotransplantation (IAT) has a potential to prevent brittle diabetes in patients after total pancreatectomy. Because of the fear of tumor spread, IAT has rarely been used in case of malignancy. We report our experience with patients who underwent hemipancreatoduodenectomy for carcinoma and later completion pancreatectomy for pancreatic fistula with islet autotransplantation at our institution. METHODS: From August 2007 to December 2012, 5 patients underwent IAT after completion pancreatectomy for pancreatic fistula after hemipancreatoduodenectomy for carcinoma. Islets were isolated from the pancreatic tail with the use of digestion with collagenase. Nonpurified islet suspension was infused into the portal vein during surgery. RESULTS: The median number of islets transplanted was 175,000 islet equivalents (range, 70,000 365,000). One patient died after surgery for reasons unrelated to IAT. Another 3 patients had stable diabetes with partial graft function (fasting C-peptide levels 0.23, 0.41, and 0.61 nmol/L and HbA1c 4.8%, 4.6%, and 6.9% at 24, 24 and 9 months after IAT, respectively). The 1st patient, with pancreatic head carcinoma, was alive 28 months after IAT with lymph node and liver recurrence since 18 months after IAT. The 2nd patient, with gall bladder and distal bile duct carcinoma, died 47 months after IAT with tumor recurrence. The 3rd patient, with ampullary carcinoma, died 12 months after IAT with local recurrence and solitary liver metastasis. The last patient had been off insulin 9 months after IAT without tumor recurrence (fasting C-peptide, 0.89 nmol/L; HbA1c, 4.2%). CONCLUSIONS: Autotransplantation of pancreatic islets isolated from the residual pancreatic tissue in patients who previously underwent hemipancreatoduodenectomy for cancer may provide stable glucose control and thus improve quality of life. In this small series we did not observe early development of multiple liver metastases caused by islet suspension contamination with malignant cells. Oncologic outcome of the patients was not worse than what would be expected without IAT. PMID- 25131093 TI - Xenograft of microencapsulated Sertoli cells for the cell therapy of type 2 diabetes mellitus in spontaneously diabetic nonhuman primates: preliminary data. AB - Insulin resistance in type 2 diabetes mellitus (T2DM) may be due to a chronic inflammation of the visceral adipose tissue (VAT) leading to local and systemic increases in proinflammatory cytokines. Microencapsulated porcine Sertoli cells (MC-pSC), by provision of immunomodulatory and trophic factors, have been successfully used to reduce such inflammation in rodent animal models of type 1 diabetes with no complications or deleterious side effects. Herein, we have begun to investigate this novel and safe therapeutic approach in the spontaneously obese nonhuman primate with spontaneous, insulin-dependent T2DM. After MC-pSC intraperitoneal injection we have evaluated, throughout a 6-month follow-up period, daily ad libitum fed glucose levels, daily exogenous insulin supplementation, biweekly body weight measurements, periodic fasting blood glucose concentrations, glycated hemoglobin (HbA1c) levels, glucose tolerance tests (GTT), and fluorescence-activated cell sorting cytometry (FACS) assessment of peripheral blood mononuclear cells. Very preliminarily, we have observed a slight reduction in fasting (FPG) and mean nonfasting (NF) plasma glucose levels. We found minimal changes, only in 1 animal, in daily exogenous insulin requirements and HbA1c levels. Flow cytometric analysis was associated with decrease in CD8(+) cells only in 1 recipient with a reduction in mean regulatory T Cells (Treg), whereas interestingly, decrease of B lymphocytes was observed in both animals. These results may suggest that this novel MC-SC-based transplantation protocol might possibly impact the metabolic status of T2DM in higher mammals that are close to humans. PMID- 25131095 TI - Resistance of spontaneously diabetic Ins2(akita) mice to allograft tolerance induced by anti-CD154 therapy. AB - BACKGROUND: Despite ongoing advances in the clinical islet transplant field, progressive decline in graft function continues to reduce the long-term success of islet transplantation for restoring euglycemia in type 1 diabetic recipients. To preserve graft function and avoid the use of chronic immunosuppressive drug therapy, a key goal is to induce donor-specific immune tolerance to islet transplants. Preclinical rodent studies of islet transplantation largely utilize models of diabetes either induced experimentally with beta cell toxins or spontaneously occurring in strains genetically prone to autoimmune diabetes. In this study, we sought to determine if chronic, severe hyperglycemia itself, independent of both beta cell toxins and host autoimmunity, influenced acute allograft rejection and/or the capacity to induce allograft tolerance. METHOD: To this end, we studied the response to islet allografts in severely diabetic, non autoimmune C57Bl/6 Ins2(akita) recipients. RESULTS: Results indicate that diabetic Ins2(akita) mice display higher levels of blood glucose, show more rapid acute islet allograft rejection, and are resistant to allograft prolongation induced with anti-CD154 therapy relative to wild-type littermates rendered diabetic with streptozotocin. As such, results suggest that severe hyperglycemia may be an independent risk factor impacting the capacity to induce tolerance to islet allografts. Thus, Ins2(akita) mice represent a stringent model for evaluating anti-rejection strategies in the setting of severe metabolic demand on islet transplants. PMID- 25131094 TI - Failure to achieve normal metabolic response in non-obese diabetic mice and streptozotocin-induced diabetic mice after transplantation of primary murine hepatocytes electroporated with the human proinsulin gene (p3MTChins). AB - BACKGROUND: A recent study by Chen et al described a therapy for diabetes that involved electroporation of primary hepatocytes with human proinsulin cDNA, p3MTChins. Intrahepatic transplantation of treated hepatocytes into streptozotocin (STZ) murine and porcine models led to euglycemia, weight maintenance, and normal insulin production. We tested the repeatability of their basic experiments and transplantation technique and expanded the study to include an autoimmune model. METHODS: Hepatocytes were isolated from B6 mice, electroporated with p3MTChins, and glucose-challenged or were injected into hepatic or spleen parenchyma of STZ-diabetic B6 and non-obese diabetic mice. Outcomes included survival, serum glucose levels, insulin, and c-peptide release. Untransfected primary hepatocytes and mice transplanted with these cells served as controls. RESULTS: p3MTChins-hepatocytes secreted insulin during glucose challenge, but glucose levels did not change with increasing glucose concentrations. Direct hepatic injection led to high mortality rates. Mice that underwent intrasplenic injection survived for >50 days (control = 4 days) and had a mild but stable improvement in hyperglycemia. C-peptide in both mouse models was detectable but eventually declined to baseline in the non-obese diabetic mice. CONCLUSIONS: Hepatocytes can be transfected with p3MTChins to produce human insulin but may lack the proper glucose-sensing or complex storage and secretion capabilities that allow for a finely tuned dynamic insulin response. Treatment is subtherapeutic, and p3MTChins-hepatocyte function may not endure in an autoimmune model. Without successful preliminary findings, cell therapy involving electroporation of p3MTChins does not appear to be practical as a therapy for diabetes and may not be a strategy to pursue at this time. PMID- 25131096 TI - Back to the reinnervation of the pancreas after transplantation? (Experimental study on dogs, cats, and rats). AB - BACKGROUND: Significant functional decrease and sclerosis of the pancreas graft in late delays cannot only be related to chronic rejection. Any transplantation leads to graft denervation, which may be an important cause of dysfunction. Studies concerning graft reinnervation were controversial. PURPOSE OF THE STUDY: The purpose of this study was to investigate the feasibility and pertinence of a surgically directed reinnervation (SDR) of denervated/neuro-reflex isolated (NRI) or autotransplanted (aTx) pancreas. BASIC PROCEDURES: Anatomy of the nerves penetrating into the pancreas was studied in humans, dogs, cats, and rats. Surgery and physiological investigations were performed in dogs, cats, and rats. Nervous conductivity between NRI, NRI+SDR pancreas, and brain was tested. Load tests with glucose, insulin, and adrenalin were performed; amylase and lipase were determined in fasted and not fasted animals to evaluate the influence of NRI and SDR on pancreatic function. Histology was provided. Observation delays were 6 months. MAIN FINDINGS: Anatomic feasibility of SDR in humans and animals was proved. Models of pancreatic tail NRI and surgical reconstitution of the interrupted nervous pathways (SDR) were elaborated in animals. The restoration of the pancreas-brain reflex axis after SDR was electro physiologically proved. As blood glucose curves after load test, exocrine amylase and lipase determination have shown that pancreas NRI or aTx leads to an exaggerated reaction to usual stimulations that may cause the observed graft functional exhaustion in late delays. SDR shortened the period of the graft neuro-reflex isolation, contributed to a quick normalization of its function, and prevented its late degradation. CONCLUSION: SDR was shown to be a simple surgical technique, easily performed after the graft surgical revascularization. Its functional and morphological efficiency was tested and proved. Thus, SDR may be recommended in human pancreas transplantation as pertinent. PMID- 25131097 TI - Surgical salvage of partial pancreatic allograft thrombosis presenting as ruptured pancreatic cyst: a case report. AB - INTRODUCTION: Vascular thrombosis is an important cause of pancreatic graft loss, and the vast majority is managed using graft pancreatectomy. There are limited reports and case series of successful salvage of the pancreas allograft. We describe a case of partial pancreatic allograft thrombosis presenting as ruptured pancreatic cyst successfully salvaged using a graft distal pancreatectomy. METHODS: We used descriptive retrospective analysis. RESULTS: A 29-year-old patient with type 1 diabetes and end-stage renal failure underwent a simultaneous pancreas kidney transplantation with immediate graft function. The cadaveric pancreas allograft was placed head up in the right iliac fossa with enteric exocrine drainage and standard vascular anastomosis. He presented with compressive symptoms on his bladder 5 months later, and a computed tomography (CT) showed a 4-cm cystic lesion in the body and tail of the pancreas allograft. Spontaneous rupture of the cyst occurred 3 weeks after the initial onset of symptoms with generalized abdominal pain. He underwent graft distal pancreatectomy with good recovery. He remains euglycemic, insulin-free with a normal renal function. Histology of the resected unhealthy graft showed an arterial thrombus with xanthogranulomatous inflammation and necrosis. CONCLUSION: Surgical salvage with graft distal pancreatectomy is feasible for partial pancreatic allograft thrombosis. Cystic lesion in the pancreas is a possible presentation of vascular thrombosis. PMID- 25131098 TI - Successful management of a ruptured mycotic pseudoaneurysm following pancreas transplantation using bovine pericardial patch: a case report. AB - Arterial mycotic pseudoaneurysms are a rare complication of pancreas transplantation. Rupture results in catastrophic hemorrhage with a high risk of mortality. Definitive management is complicated by an extensive arterial defect within a contaminated surgical field. Synthetic vascular grafts often fail due to subsequent graft infection whereas primary repair often results in arterial stenosis. Arterial ligation may be required to prevent exsanguination. A 41-year old man, type 1 diabetic with associated renal failure, underwent successful simultaneous pancreas and kidney transplantation. He presented, 9 months following transplantation, with life-threatening rectal bleeding secondary to a ruptured mycotic pseudoaneurysm. This was successfully managed with a bovine pericardial patch (BPP) repair of the arterial defect and enteric diversion following graft pancreatectomy. He remains well with no vascular insufficiency 18 months following the procedure. A ruptured mycotic pseudoaneurysm following transplantation carries a significant risk of mortality and represents a surgical challenge as conventional techniques using synthetic materials often fail due to the contaminated field. A BPP offers good handling characteristics, excellent hemostatic properties and a favorable profile of infection risk in comparison with synthetic grafts. This case highlights its use as a treatment for a post transplantation ruptured mycotic pseudoaneurysm. PMID- 25131100 TI - Donor organ shortage crisis: a case study review of a financial incentive-based system. AB - INTRODUCTION: Current organ supply system depends on altruistic noncoercive donation, which has failed to meet the demand of organ transplantation. Providing financial incentives to donors is one of several approaches to address organ shortage. However, its feasibility is debatable as it relates to medical, ethical, and economic dimensions. An incentive-based procurement system (IBPS) applied by the Mobile Donor Action Team (MDAT) was instituted in Riyadh, Saudi Arabia, resulting in a 3-fold increase in donation rate. The goal of this study was to provide a qualitative review of a 7-year experience with IBPS. MATERIALS AND METHODS: A qualitative approach was used. Documents were reviewed to create a chronological audit and shape interview questions. Sampling was purposeful and inclusive of MDAT members. Semi-structured interviews were conducted, and findings were subjected to thematic analysis. RESULTS: Documents reflected the evolution of MDAT. The essence of MDAT is field work and liberal use of financial incentives, which resulted in a 3-fold increase in the donation rate. MDAT members believed that IBPS is the main reason behind this increase. Moreover, IBPS is viewed as acceptable from a moral, ethical, and religious standpoint, with a high degree of professional satisfaction. CONCLUSIONS: Theoretical assumptions doubted the feasibility of IBPS. This real-life experience with IBPS proved the contrary. The findings may be applicable only to the setting in Riyadh, Saudi Arabia, however; further research is thus needed to explore its transferability to other settings. IBPS may be an alternative to altruistic noncoercive donation and should be piloted in different settings. PMID- 25131101 TI - Communication with family after loss, in the context of transplantology. AB - BACKGROUND: Cooperation with a patient is a joint venture, based on a division of power and authority. Its character is not hierarchical. It assumes that this power is based on knowledge and experience, which is the opposite of power based on role or position. The good doctor-patient relationship affects a range of factors, including the healing process, the possibility of understanding the causes of a disease and its treatment and in a broader perspective, trust in the health service, which can in turn have a positive influence on public attitudes to organ donation. Because consent is presumed in Poland, there is no family consent requirement for organ donation of a deceased family member. In practice, however, medical professionals usually strive to get consent from family members, and in cases of refusal, they will not harvest. The aim of our study was to answer the following questions: (1) Does the way in which care was provided for the still-alive patient, as well as the relationship between the doctor and the patient's family, influence the family's decision to agree to the harvest of the dead patient's organs? (2) Does previous experience with healthcare institutions and personnel influence their decision to agree to organ donation? METHODS: Research was conducted on a group of 173 people, using a questionnaire comprising 18 questions. RESULTS: Obtained results show that 34% of people are satisfied with the level of medical care. The majority claim that doctors treat them without due care. Thirty-eight percent believe that doctors are capable of stopping therapy in order to get organs for transplantation. CONCLUSIONS: It is necessary to recognize the correlation between a correct doctor-patient relationship, gaining trust, and how reliable a doctor's opinions are. A patient's conviction that he or she is well treated may lead to regaining the belief in the straightforwardness of the doctor's opinion, and less dissatisfaction with and less criticism of medical care. PMID- 25131102 TI - Organ donation: new hope through the expected amendment in Germany? AB - INTRODUCTION: The current organ donor shortage in Germany results in the death of 1000 patients on the transplant waiting list every year. In response, a recent amendment to the German Transplant Act aiming to increase donor rates was passed. Among a number of other measures, Germans are asked to decide whether they choose to donate organs or not in the event of a brain death or whether they would like to designate someone who should decide for them in this situation. The objective of this study was to collect and evaluate data on the public's attitude toward organ donation before the expected amendment. METHODS: A survey on the subject of organ donation was conducted in 2011 among clients of a public pharmacy in a major city in the federal state North Rhine-Westphalia, Germany. Data regarding sex, age, health behavior, and attitude toward the amendment were collected and association organ donor card possession was analyzed. RESULTS: A total of 1485 questionnaires were evaluated. Of those surveyed, only 14.1% had an organ donor card. No statistically significant associations between sex (P value .3045), age (P value .1453) and the possession of a donor card were observed. We found that 72.5% of respondents stated that they appreciated the expected amendment, and in the case of implementation, the majority would obtain an organ donor card. DISCUSSION: The future success of transplantation medicine relies on an increase in the public's overall willingness to donate organs. Educating the public and ensuring transparency in transplantation medicine are vital to achieving higher donation rates. The new German transplantation act may be an important step to increase society's awareness and participation in organ donation. PMID- 25131103 TI - Islamic founding principles on organ transplantation and the evolution of Islamic scholarly opinions on the subject. AB - BACKGROUND: Muslims constitute about one-fourth of the human population, and a significant fraction of the organ recipients identify themselves as Muslims. A large fraction of the Muslim population is devout but unclear regarding the religious principles on organ donation and transplantation and is dependent on scholars' and imams' opinions. METHODS: The Qur'an, the authentic Prophetic Traditions, and expert opinions on the subject were investigated. RESULTS: The sources of the Islamic founding principles on organ donation and transplantation are the Qur'an, the Prophetic Traditions, Usulul Fiqh or expert opinions based on the Qur'an and Traditions, and Maslaha or the principles of public interest deduced by the scholars. Some Muslim scholars, mostly from the Indian subcontinent, opine that live organ donation, extraction of organs from dead persons, and transplantation are prohibited. Many Arab scholars and Muslim scholars settled in the western hemisphere opine that live organ donation, organ extraction from dead persons, and transplantation are permitted, but organ donation must be a voluntary act of charity. Of late, the Iranian imams/scholars have recognized that the national government may acquire live donor organs for a uniform compensation and equitably distribute the acquired organs to patients with failing organs. CONCLUSIONS: The current Islamic working principles on transplantation medicine are nonuniform, transitory, and somewhat detached from the bulk of the population. How such heterogeneity is affecting transplantation medicine, and organ donation in particular, among Muslim populations warrants further investigation. PMID- 25131104 TI - Motivation for organ donation among college students in the United States. AB - BACKGROUND: The majority of the patients presently waiting for an organ are waiting for a kidney. Living kidney donation by about 0.1% of the adult population of a nation may completely eliminate kidney shortage. We investigated the concerns of college students toward charitable and compensated organ donation. METHODS: A 40-question survey was conducted. The respondents were students of the Biology Department of Utah Valley University, Orem, Utah, United States. The data were tabulated and analyzed. Tests of association among potentially linked attributes and the difference between two independent proportions were performed at the 0.05 level of significance and P-values were also calculated using XLSTAT software. RESULTS: The participants (n = 321) were 47% male, 53% female, 89% Caucasian, and 93% healthy, and 7% of the respondents had some health conditions. Of the respondents, 55% were ages 18 to 25 and 40% were ages 26 to 50 years; 43% were unmarried or single, 57% were married, and 85% had health insurance. About 65% of the respondents lived in small cities and the rest lived in large cities (23%) or the countryside (9%). There was no significant association between gender, level of education, location of living, and household income in relation to belief in organ donation with or without compensation, except that males favored compensated organ donation over females (P = .004). Rumors on organ theft and extraction of organ from questionable brain dead patients had not negatively affected the decision of participants on being listed as organ donors in their driver's license (P = .0001). Those who considered organ donation ethically acceptable also believed that a person has the right to sale a kidney (P = .015) and the donor party should be somehow compensated (P = .001). CONCLUSIONS: A large percentage of college students supports compensated organ donation and considers that compensation will increase organ donation. PMID- 25131105 TI - Heart donation in Japan before and after the revision of the Japanese Transplantation Act. AB - INTRODUCTION: After the revision of the Organ Transplant Act in July 2010, brain dead organ donation increased from 13 to 45 per year, and heart donation increased. The purpose of this study was to review 166 consecutive brain dead heart donors to evaluate our strategies to identify and manage organ donors. METHODS: This study reviewed 166 consecutive brain dead heart donors since the Act was issued. Whereas 69 heart donations were performed between October 1997 and July 2010 before the revision of the Act, 97 heart donations were performed for the 3 years after the revision. Since November 2002, special transplant management doctors were sent to donor hospitals to assess donor organ function and to identify which organs could be transplanted. They also intensively cared for the donors to stabilize hemodynamics and to improve cardiac function by giving intravenous antidiuretic hormones and by pulmonary toileting via bronchofiberscope. RESULTS: The mean heart donor age increased from 41.0 to 43.9 years after the revision. Notably, 11 hearts from donors more than 60 years old were transplanted successfully after the revision. Before the revision, the cause of death was 37 cerebrovascular disease (SAH 34, stroke 1, bleeding 2), 18 head trauma, 13 asphyxia, and 2 postresuscitation brain damage. After the revision, there were 49 cerebrovascular disease (SAH 37, stroke 2, bleeding 16, and other 4), 17 head trauma, 10 asphyxia, and 11 postresuscitation brain damage. A total of 58 donors had a history of cardiac arrest, 58 required a high dose of catecholamine drip infusion, and only 1 recipient died of primary graft dysfunction. Patient survival rate at 3 years after heart transplantation was not different before and after the revision of the Act (98.6% vs 92.2%). CONCLUSIONS: Although donor age was increased and donors who died of cerebral bleeding or postresuscitation after the revision of the Act increased, the outcome after heart transplantation was not changed. PMID- 25131106 TI - Regional variation in organ donation in Saudi Arabia. AB - INTRODUCTION: There is marked regional variation in organ donation among the different regions of Saudi Arabia. Our aim was to study the dominating factors for these variations to improve organ donation in low-donation areas. MATERIALS AND METHODS: This study was a retrospective review of the Saudi Center for Organ Transplantation data for cadaveric organ donation from 2006 to 2012, with the number of cases reported, documented, consented, and harvested in various regions (northern, southern, eastern, western, and central). The region, number, and size of contributing intensive care units (ICUs), overall donation rate, and transplanted rate (potential donor and those harvested, respectively) were also reviewed. RESULTS: Between 2006 and 2012, a total of 512 cases were procured and analyzed from Saudi Arabia. From the central region, 393 were acquired, representing 76.7% of the total consented cases. These 393 cases came from 30 of 97 contributing ICUs (31%). The eastern region was ranked second, followed by the western region. The conversion rate for all regions followed a similar trend. CONCLUSIONS: There is marked variation with regard to organ donation in different regions throughout Saudi Arabia, from 1.9% in the southern region to 76.7% in the central region. This finding is related to the presence of a Mobile Action Donor Team in the central region. The number of potential donors and the contributing ICUs were strong predictors of the number of actual donors. We suggest that having a mobile donor team in each region will increase the number of donors by at least 3 times within the next 3 to 5 years. PMID- 25131107 TI - Successful international collaboration improves family donation conversations resulting in increased organ donation. AB - INTRODUCTION: Australian donation leaders recognized that to increase organ donation outcomes, health professionals conducting family donation conversations (FDCs) required support and specialist training. An international training institute with programs based on proven results was engaged to create and implement a customized training program to influence change in FDC practice and culture. The goal was to increase donation rates by developing and implementing a customized, self-sustaining training program to enhance FDC practices of health professionals. Other goals included providing training and communications skills to lead FDC, supporting families in making decisions, and influencing health professionals to adopt FDC practices. MATERIALS AND METHODS: To gain support and determine program suitability, two 1-day pilot training sessions were provided to 45 Australian donation leaders in 2011. Training was further customized with an emphasis on creating changes to achieve and sustain desired results. A comprehensive national training plan was implemented over 18 months. Twenty-six 2 day FDC training workshops were held in 8 cities (646 participants). Program evaluations and debriefings showed distinct shifts in perspectives and an enthusiasm to implement new processes. In 2012 to 2013, an instructor program was developed to transition training facilitation. The training institute remains involved in development and training to build and sustain skill and expertise. RESULTS: There was a 58% increase in organ donors in Australia from 2009 to 2013 (data reflect 2013 Australian end-of-year organ donation information). This represents a 36% increase in organ donors (2009-2011); the remaining 22% increase was achieved in the 2 years since the FDC training was implemented in Australia (2011-2013). CONCLUSIONS: Improved skills training in the conduct of FDCs seem to have contributed to improved donation outcomes in national identification, request, and consent rates. The integration of another organization's process poses distinct challenges; thoughtful collaboration, sensitive to cultural aspects and family care, communication, and donation practices, can result in successful customized training that shifts perspectives, provides new skills, and achieves and sustains an increase in organ donation rates. PMID- 25131108 TI - In-house coordination for organ donation--single-center experience in a pilot project in Germany (2006 to 2013). AB - A challenge for solid organ transplantation in Germany is the shortage of organs. In an effort to increase donation rates, some federal states mandated hospitals to install transplantation officers to coordinate, evaluate, and enhance the donation and transplantation processes. In 2009 the German Foundation for Organ Transplantation (DSO) implemented the In-House Coordination Project, which includes retrospective, quarterly, information technology-based case analyses of all deceased patients with primary or secondary brain injury in regard to the organ donation process in maximum care hospitals. From 2006 to 2008 an analysis of potential organ donors was performed in our hospital using a time-consuming, complex method using questionnaires, hand-written patient files, and the hospital IT documentation system (standard method). Analyses in the In-House Coordination Project are instead carried out by a proprietary semiautomated IT tool called Transplant Check, which uses easily accessible standard data records of the hospital controlling and accounting unit. The aim of our study was to compare the results of the standard method and Transplant Check in detecting and evaluating potential donors. To do so, the same period of time (2006 to 2008) was re evaluated using the IT tool. Transplant Check was able to record significantly more patients who fulfilled the criteria for inclusion than the standard method (641 vs 424). The methods displayed a wide overlap, apart from 22 patients who were only recorded by the standard method. In these cases, the accompanying brain injury diagnosis was not recorded in the controlling and accounting unit data records due to little relative clinical significance. None of the 22 patients fulfilled the criteria for brain death. In summary, Transplant Check is an easy to-use, reliable, and valid tool for evaluating donor potential in a maximum care hospital. Therefore from 2010 on, analyses were performed exclusively with Transplant Check at our university hospital. PMID- 25131109 TI - Exchange of best practices within the European Union: surgery standardization of abdominal organ retrieval. AB - Considering the growing organ demand worldwide, it is crucial to optimize organ retrieval and training of surgeons to reduce the risk of injury during the procedure and increase the quality of organs to be transplanted. In the Netherlands, a national complete trajectory from training of surgeons in procurement surgery to the quality assessment of the procured organs was implemented in 2010. This mandatory trajectory comprises training and certification modules: E-learning, training on the job, and a practical session. Thanks to the ACCORD (Achieving Comprehensive Coordination in Organ Donation) Joint Action coordinated by Spain and co-funded under the European Commission Health Programme, 3 twinning activities (led by France) were set to exchange best practices between countries. The Dutch trajectory is being adapted and implemented in Hungary as one of these twinning activities. The E-learning platform was modified, tested by a panel of Hungarian and UK surgeons, and was awarded in July 2013 by the European Accreditation Council for Continuing Medical Education of the European Union of Medical Specialists. As a pilot phase for future national training, 6 Hungarian surgeons from Semmelweis University are being trained; E-learning platform was fulfilled, and practical sessions, training-on-the-job activities, and evaluations of technical skills are ongoing. The first national practical session was recently organized in Budapest, and the new series of nationwide selected candidates completed the E-learning platform before the practical. There is great potential for sharing best practices and for direct transfer of expertise at the European level, and especially to export this standardized training in organ retrieval to other European countries and even broader. The final goal was to not only provide a national training to all countries lacking such a program but also to improve the quality and safety criteria of organs to be transplanted. PMID- 25131110 TI - Study of education program of in-hospital procurement transplant coordinators in Japan. AB - BACKGROUND: As the number of donated organs is still extremely small in Japan compared with other developed countries, in-hospital procurement transplant coordinators (In-Hp PTC) may play an important role in increasing organ donation and making the procurement procedure smoother. In this study, our education program of In-Hp PTC is described. MATERIALS AND METHODS: In May 2012, our department started the In-Hp PTC Education Program. In the first semester, a 2 hour lecture is provided every 2 weeks for 5 months to 15 In-Hp PTCs working near Osaka. In the second semester, 20 lectures were provided for 3 consecutive days to 31 In Hp PTCs, more than 80% of whom work far from Osaka. Lecture topics were the history and current status of organ donation in Japan, social regulation of organ donation, care of transplant recipients, overall procedures of organ donation, the role of In-Hp PTC, donor family care, donor indications, and donor assessment and management. Lectures also included simulations of the organ donation process. RESULTS: Participants were surveyed for their opinions after the program, Most participants were satisfied with the program, topics and duration. As most of them are not full-time In-Hp PTCs, they preferred to attend the 3-day program. Many participants are currently working as main In-Hp PTCs and establishing their own organ donation system in their hospital. CONCLUSIONS: In Hp PTCs have an important role to play in establishing an organ procurement system and increasing organ donation in Japan. This program may help establish a systematic education program for this occupation in Japan. PMID- 25131111 TI - The impact of interleukin 12B (1188A>C), interleukin 16 (-295T>C), and interleukin 18 (607C>A, 137G>C) gene polymorphisms on long-term renal transplant function and recipient outcomes. AB - BACKGROUND: Inflammatory mediators play an important role in kidney graft outcome. The cytokine and chemokine gene polymorphisms are associated with variable production, activity, expression, or ligand-receptor affinity. Genetic variation in the DNA sequence of the interleukin 12B (IL12B), interleukin 16 (IL16), and interleukin 18 (IL18) genes may lead to altered cytokine production and activity. These variations can lead to changes in individual patient outcomes after kidney transplantation. It is known that polymorphisms of interleukins have an influence on inflammatory diseases, eg, Crohn's disease, diabetes, and asthma. AIM: The aim of this study was to evaluate the correlation between IL12B, IL16, and IL18 gene polymorphisms with delayed graft function (DGF), acute rejection episodes (AR), and chronic rejection episodes (CR). MATERIALS AND METHODS: A total of 267 (38.6% women, 61.4% men) recipients were included in the study. Cadaveric kidney transplantations were performed at the Department of General Surgery and Transplantation. Polymerase chain reaction was used to determine gene polymorphisms of IL12B (rs3212227), IL16 (4778889), and IL18 (rs1946518, rs187238) in 2 mL of serum. Statistical significance (P < .05) was analyzed by logit regression, ANOVA and odds ratio (OR) of chi(2) with Yates correction (95% confidence interval). RESULTS: Regression analysis revealed no significance between AR/DGF/CR and IL-2B, IL16, IL18rs1946518, and IL18-rs187238 (P > .05). The CR group, AA vs CC genotype of IL18 (rs1946518), had an OR = 2.35 (P = .04). AR and DGF groups had no significance in OR. CONCLUSIONS: There was no statistical significance between IL12B, IL16, and IL18 (rs187238) gene polymorphisms and kidney graft outcome after transplantation. Presence of AA genotype (IL18-rs1946518) is connected with a 2.35 times higher risk of CR occurrence. PMID- 25131112 TI - Reuse of a previously transplanted kidney from a deceased donor using Luminex virtual crossmatching: a case report. AB - Kidney transplantation is the most desired modality of renal replacement therapy for patients with end-stage renal disease (ESRD). We have attempted to expand the organ donor pool through several methods, including the use of expanded donor criteria. Although previously transplanted kidneys are rarely reused, they can be suitable for transplantation into patients in need. We report a case of successful reuse of a previously transplanted kidney from a deceased donor by means of Luminex virtual crossmatching with the first donor and actual crossmatching with the second donor. PMID- 25131115 TI - Histologic evaluation of organ preservation injury and correlation with cold ischemia time in 13 intestinal grafts. AB - Lesions produced in the graft mucosa due to harvesting, storage, and implantation must be graduated to assess the subsequent protocolized biopsy specimens. The aim is to identify type and intensity of graft mucosal lesions observed immediately after implantation. Congestion, hemorrhage, microthrombi, neutrophilic infiltrates, shortening of villi, epithelial detachment, erosion, and crypt loss were separately evaluated by two pathologists in mucosal biopsy specimens from 13 grafts. Each change was assessed as normal, mild, moderate, or severe and by splintering the summation of points a global score was designed. Cold ischemia time was registered. Correlation between the pathologists' evaluations and between final preservation injury degree and cold ischemia time was determined using the "index of correlation rho (rho)" (Spearman's test). The same changes were assessed in 19 biopsy specimens from day 2 to day 6 (3.6 +/- 1.1) to determine their evolution. Congestion was found in 7 biopsy specimens, microthrombi in 2, hemorrhage in 4, neutrophils in 6, villous atrophy in 8, epithelial detachment in 9, erosions in 2 and/or crypt loss in 2. The maximum degree of preservation injury was expressed as intense congestion and hemorrhage associated with epithelial detachment and villous atrophy. The global preservation score was grade 3 in 2 cases, grade 2 in 5, grade 1 in 2, and grade 0 in 4. There was positive correlation (rho = 0.915) in the evaluation between pathologists (P < .01), total agreement in 9 biopsy specimens, and partial agreement (only 1 point disagreement) in 4. Mean cold ischemia time was 327 +/- 101 min. (135-480). There was positive correlation (rho = 0.694) between preservation score and cold ischemia time (P < .01). In the follow-up biopsy procedures, histological injury decreased by at least one grade in every case. Additionally, karyorrhexis was observed in 3 grafts and very occasional apoptosis in 2 others. This scale achieves good reproducibility and allows graduate preservation injury in intestinal transplantation. PMID- 25131114 TI - Short- and long-term outcomes of every graft recovered during a multi-organ procurement procedure including the intestine. AB - BACKGROUND: The development of intestinal transplant (Tx) programs introduces thymoglobulin donor treatment as well as an almost complete warm dissection of the abdominal organs to allocate them to different recipients. Our aim is to assess the reproducibility and feasibility of the surgical technique of multi organ procurement with the use of thymoglobulin donor pre-treatment and report the short- and long-term outcomes of every graft harvested as part of multi-organ procurement (MTOp), including the intestine. METHODS: Data were collected of all organs harvested from MTOp, including the intestines allocated to our center from March 2006 to July 2011. Data from 92 recipients and 116 organs procured from 29 MTOp were analyzed. Twelve hearts, 2 lungs, and 1 cardio-pulmonary block were transplanted; primary graft dysfunction developed in 4 of the 12 hearts and in the cardio-pulmonary block. RESULTS: The survival rate was 75% and 100% for hearts and lungs, respectively. Nineteen livers, 9 kidney-pancreas, 19 kidneys, and 29 intestines were transplanted. Delayed graft function (DGF) of the pancreas developed in 3 of 9 kidney-pancreas, and the other 3 exhibited DGF of the kidney; 4 of 19 Tx kidneys had DGF. The survival was 84%, 78%, 95%, and 65.5% for livers, kidney-pancreas, kidneys, and intestines, respectively. CONCLUSIONS: Organs procured during MTOp including the intestine can be safely used, increasing organ availability and transplant applicability without compromising allocation, quality, and long-term results of the non-intestinal-procured organs. PMID- 25131116 TI - Histologic evaluation of post-implantation immediate C4d deposition in 13 intestinal grafts: correlation with cell-based crossmatching, cold ischemia time, and preservation injury. AB - C4d deposits are predictive of humoral rejection in kidney and heart transplantation. The aim of this study was to identify C4d deposit patterns in intestinal mucosa of the grafts on biopsy specimens obtained immediately after implantation and to detect if it could be a valuable tool to predict humoral or acute rejection. A second objective was to search for a statistically significant relationship between positive C4d deposition and other collected variables. Thirteen immediately post-transplantation mucosal graft biopsy specimens, formalin fixed, underwent immunohistochemical stain for C4d deposits. Diffuse intense staining of capillary endothelium was considered positive and absent, focal or weak stains as negative. Preservation injury grade and cold ischemia times were registered for each case. Donor-specific preformed antibodies were detected by complement dependent cytotoxicity serologic technique (crossmatching). Another 19 endoscopic follow-up biopsy specimens from days 2 to 6 were also evaluated. Statistical studies were made using the index of correlation rho (Spearman's test). Diffuse intense C4d deposits were observed in 2 grafts, focal and weak in 5, and completely negative in 6. The mean cold ischemia time was 327 +/- 101 minutes. Two cases showed diffuse positive deposits, 1 had a positive crossmatch and the cold ischemia time was 360 minutes whereas the other had not preformed antibodies and its cold ischemia time was 475 minutes. Humoral or acute rejection was not observed in follow-up mucosal biopsy specimens. There was no statistically significant relationship between the C4d deposition, cold ischemia time, crossmatching results, and preservation injury degree. In conclusion, C4d deposition was not a helpful tool for diagnosis of humoral rejection and prediction of acute rejection during the early post transplantation period. PMID- 25131117 TI - A surgical perspective of the outcome of a multidisciplinary intestinal rehabilitation program for children with short bowel syndrome in The Netherlands. AB - AIM: In 2001, a multidisciplinary intestinal rehabilitation program, prompted by a nationwide collaboration on intestinal failure (Dutch Registry for Intestinal Failure and Intestinal Transplantation), was started for children who have short bowel syndrome (SBS). This study evaluates this program, focusing on children who have SBS after extensive bowel resection. DESIGN: This is a retrospective cohort study. METHOD: Demographic data, general information on disease status, and outcome of intestinal rehabilitation of patients treated between 2001 and 2009 were collected. Outcome measures were intestinal autonomy, intestinal and/or liver transplantation, and survival. RESULTS: Ten boys and 9 girls, median gestational age 36 weeks, were treated. Eight were referred, 3 times as many as in the period 1991-2000. Causes of SBS were intestinal atresia (3), gastroschisis (2), volvulus (9), necrotising enterocolitis (3), and strangulation (2). The median remaining small-intestinal length was 35 cm (range, 10 to 70 cm). In 14 patients the ileocecal valve was still present. In all patients at least 25% of colon was still present. The median follow-up was 25 months (range, 50 days to 9 years). After a median of 138 days (range, 41 days to 11 years) on total parenteral nutrition, 16 patients (84%) reached intestinal autonomy. Central venous catheter-related complications occurred in all; there were liver function disorders in 68%, and a failure to thrive in 26%. One patient underwent intestinal lengthening. No patient needed intestinal transplantation, but one underwent liver transplantation for intestinal failure-associated liver disease. Overall mortality was 11%: those 2 patients died of abdominal sepsis. CONCLUSION: This specialized intestinal rehabilitation program led to intestinal autonomy in 84% of the patients who had SBS. None of the patients underwent an intestinal transplantation. PMID- 25131118 TI - Quality of life and performance status before and after small intestinal transplantation. AB - INTRODUCTION: Intestinal transplantation (IT) is considered for patients with irreversible intestinal failure who develop life-threatening complications of parenteral nutrition or have extensive intra-abdominal disease requiring evisceration. Developing indications may include quality of life (QOL) considerations and therefore assessment of QOL and performance status (PS) after IT is important. We report QOL and PS before and after IT in our cohort. METHODS: Consecutive patients undergoing IT were included. QOL was assessed using the generic 36-item short form survey (SF 36) tool at assessment and 6-month intervals post-transplantation. Performance was assessed using a visual analogue scale (VAS), Karnofsky scale (KS), and the Eastern Cooperative Oncology Group scale at three time points: premorbidly, at listing, and after transplantation. RESULTS: Data were available for 21 patients. There were 11 complete SF 36 datasets and 15 performance scores. Data were not available from 3 patients, and the overall response rate was 62%. Overall, there was a trend for improved SF 36 scores post-transplantation in approximately half of the patients with scores remaining stable in approximately one third. The results of the SF 36 significantly improved in 1 patient (P < .01). After IT, 66% of patients had better VAS scores than at listing and >75% of patients scored better or the same in KS compared to status at listing. However, PS after IT did not improve to premorbid levels. CONCLUSION: We found a trend for QOL scores to improve in approximately half of the patients compared to their status at listing, remain static in approximately one third, and a minority experience a decline. For the majority, differences were not statistically significant. PS of patients after transplantation is equal or better than that at listing in 75%, but rarely reaches that of the premorbid status. Longer-term studies are needed and may reveal progressive improvement. PMID- 25131119 TI - Adult small intestinal and multivisceral transplantation: lessons through the "retrospecto-scope" at a single UK centre from 1991 to 2013. AB - The first intestinal transplantation in the United Kingdom was performed in Cambridge in 1991. Thirty-eight intestinal transplantations have since been performed in 35 patients. All deaths in the first postoperative month related to hemorrhage, in 2 cases to severe portal hypertension (SPH) and poor venous access in 2. We have modified our practice to reduce the bleeding risk with SPH. Loss of venous access can be avoided by timely referral. Rejection was implicated in 3/14 deaths all dying of sepsis. Cytomegalovirus disease resulted in 2 deaths; we try to avoid CMV-positive donors giving to CMV-negative recipients. Three deaths were related to psychiatric illness, which led to loss of graft in 2 others. Three patients were retransplanted (2 rejections and 1 infarction) and all remain alive. Most patients (10/13) experienced a fall in body weight in the first postoperative year after SB/MV transplantation. Body weight fell by as much as 25%. As transplantation resulted in a net gain in small bowel in most cases, the postoperative loss of native body weight may be underestimated. Interestingly this was not associated with a significant fall in midarm circumference or handgrip strength. Long-term nutrition can be maintained with oral intake in the majority of patients post-SBT. There is improvement in handgrip strength post transplant. Transplantation does not significantly alter weight, albumin, or other common anthropometric markers. Despite these problems, our 5-year survival results remain relatively good at 73% in the cohort from 1991, 79% from 2003, and 80% from 2008. We consider that deployment of strategies learned from our experiences has improved outcomes. PMID- 25131120 TI - Selenium homocholic acid taurocholate scanning, selenium-75-labeled bile acid, a novel method for testing the function of the terminal ileum in small bowel transplant recipients: a pilot study. AB - INTRODUCTION: The terminal ileum (TI) is important for the active reabsorption of bile salts and is the site of allograft rejection; disruption of enterohepatic circulation (EHC) may give insights to inflammatory and other physiologic processes at the TI. SUBJECTS AND METHODS: Four children aged 5 to 12 years who had received small bowel transplantation (SBTx), 3 recovering from post transplant lymphoproliferative disease (PTLD) and 1 with acute rejection, were studied. Two of the 4 had stoma reversal. Another child (15 years) with progressive familial intrahepatic cholestasis (PFIC) and pruritus, despite liver transplantation and biliary diversion, was studied. Selenium homocholic acid taurocholate scanning ((75)SeHCAT) capsule was given orally (n = 3) or via introducer during endoscopy (n = 2); a baseline whole-body gamma camera scan was done 4 hours later and on days 1 to 5. RESULTS: The normal 3-day bile salt retention is 30% to 70% of baseline and normal adult biological half-life, t1/2 is 62 +/- 17 hours. The results in children with a stoma were very low (0.1% at 7.6 hours; 5% at 17 hours). The children with reversed stoma had retention and t1/2 closer to the reference range (18% at 29 hours; 22% at 33 hours). The child with PFIC + biliary diversion had an initial very high gamma emission from the stoma bag suggesting excellent reabsorption of bile salts from his TI, but retention was 0.6% and t1/2 9.8 hours, demonstrating efficient biliary diversion. CONCLUSION: These results confirm children with stomas malabsorb bile acids, which can be ameliorated after stoma closure. SeHCAT demonstrated that the biliary diversion was working well and may be helpful in preoperative assessment of abnormal EHC. The role of SeHCAT in SBTx requires further evaluation. PMID- 25131121 TI - Impact of intestinal transplantation for intestinal failure in Japan. AB - INTRODUCTION: The prognosis of intestinal failure has improved dramatically in the past few decades with the development of parenteral nutrition (PN). However, PN-dependent patients still have numerous complications. Intestinal transplantation can significantly improve their prognosis and quality of life. We report on the impact of intestinal transplantation for intestinal failure in Japan. METHODS: Intestinal transplantations have been performed in Japan since 1996. Standardized forms were sent to all known intestinal transplantation programs, asking for information on intestinal transplantations performed between 1996 and June 31, 2012. All programs responded. Patient and graft survival estimates were obtained using the Kaplan-Meier method and analyzed with the Wilcoxon statistic. RESULTS: Five institutions provided data on 24 grafts in 21 patients. There were 12 cadaveric and 12 living related donor transplants. Causes of intestinal failure included short gut syndrome (n = 9), intestinal motility function disorders (n = 11), retransplantation (n = 3), and other (n = 1). The overall 1- and 5-year patient survival rates were 86% and 68%, respectively. In cases (n = 15) after 2006, the 1-year patient survival rate was 92%, and the 5 year survival rate was 83%. One- and five-year graft survival rates were 87% and 78%, respectively. More than 80% of all current survivors discontinued PN. CONCLUSIONS: Intestinal transplantation has become an effective therapy for patients with intestinal failure who cannot tolerate PN. After 2006, patient and graft survival rates approached rates associated with standard treatment for end stage intestinal failure. Further improvements are expected with early referral due to suitable donor organ and pretransplant management. PMID- 25131122 TI - Evaluation of epithelial chimerism after bone marrow mesenchymal stromal cell infusion in intestinal transplant patients. AB - Intestinal transplantation is the most effective treatment for patients with short bowel syndrome and small bowel insufficiencies. We evaluated epithelial chimerism after infusion of autologous bone marrow mesenchymal stromal cells (BMSCs) in patients undergoing cadaveric donor isolated intestinal transplantation (I-ITx). BMSCs were isolated from patients' bone marrow via iliac puncture and expanded in vitro prior to infusion. Two out of the 3 patients were infused with autologous BMSCs, and small intestine tissue biopsies collected post operatively were analyzed for epithelial chimerism using XY fluorescent in situ hybridization and short tandem repeat polymerase chain reaction. We observed epithelial chimeric effect in conditions both with and without BMSC infusion. Although our results suggest a higher epithelial chimerism effect with autologous BMSC infusion in I-ITx, the measurements in multiple biopsies at different time points that demonstrate the reproducibility of this finding and its stability or changes in the level over time would be beneficial. These approaches may have potential implications for improved graft survival, lower immunosuppressant doses, superior engraftment of the transplanted tissue, and higher success rates in I-ITx. PMID- 25131123 TI - Prothrombotic disorders in a cohort of 25 patients undergoing transplantation: investigation and management implications. AB - BACKGROUND: Many patients referred for intestinal transplantation have a history of thrombosis. We undertook an analysis of transplanted patients to describe the history and frequency of thrombosis, clinical course, and management strategies used. RESULTS: Twenty-five patients underwent transplantation of intestine containing blocks between 2007 and 2012; 20 of 25 are still alive. Five of 25 patients were transplanted with history of portomesenteric thrombosis, 6 of 25 had experienced loss of venous access due to thrombosis, and 6 of 25 had history of mesenteric ischemia. Pretransplantation, 16 of 25 patients were anticoagulated. Thrombophilia screens identified 3 of 16 patients who were JAK2 positive, 1 of 25 who had antithrombin deficiency, and 1 of 25 who had a factor V Leiden heterozygote. Post-transplantation, of all 16 patients who were anticoagulated pretransplantation and continued postoperatively, 1 of 16 infarcted their small bowel graft and 4 of 16 developed a further venous thrombosis despite anticoagulation. Of the 9 without a previous history of thrombosis, 1 had a pulmonary embolus more than a decade after transplantation and another had an upper limb deep vein thrombosis associated with a line. Both were then anticoagulated. Seven of 25 are not anticoagulated, although they are administered antiplatelet prophylaxis. Postoperative bleeding complications of anticoagulation occurred in 3 patients. After a subarachnoid hemorrhage in 1 of those 3 patients, anticoagulation was stopped. The other 2 patients bled during ileal biopsy, and both remain on low molecular weight heparin treatment. CONCLUSION: Those with identifiable thrombophilic tendency and a history of venous or arterial thrombosis are considered to be at high risk for recurrent thrombosis. Those without such a history could be considered low risk. Our practice is to anticoagulate all high-risk individuals before and after transplantation and offer antiplatelet prophylaxis to low-risk patients as the risk of anticoagulation probably outweighs the risk of thrombosis for them. Early input from hematologists is vital in the management of high-risk patients, particularly those who thrombose when anticoagulated. PMID- 25131124 TI - Psychiatric disorders in patients undergoing intestinal transplantation. AB - BACKGROUND: Psychiatric disorders are common in chronic disease states; intestinal transplantation recipients may therefore be at high risk for psychiatric disorder (PD). We sought to investigate the frequency and type of PD in our cohort of patients undergoing transplantation between 2007 and 2012. RESULTS: The notes of 25 patients who had undergone transplantations since 2007 were available for analysis. Five of 25 patients had died at the time of data collection. Pretransplantation, 14 of 25 patients had a history of a single psychiatric disorder (SPD) (depression). Two of 25 had double psychiatric diagnoses (DPD; depression with anxiety), and 1 had three PDs. Three of 25 patients suffered from chronic pain syndrome and 1 patient had this as an isolated diagnosis without any other PD. Post-transplantation, 10 of 14 patients still had an SPD; however, 3 of 14 had acquired a second diagnosis (DPD; anxiety with depression) with suicidal ideation in 2 cases. Those with DPD preoperatively did not improve. Depression resolved in 1 of 14 after transplantation. One patient without a history of psychiatric issues developed DPD during the postoperative course. Only 3 of 25 surviving patients are free of any psychological diagnosis post-transplantation. The presence of other problems in the cohort such as chronic pain syndrome in 4 of 25, medical noncompliance in 3 of 25, cyclizine dependency in 2 of 25, and recreational drug use suspected in 1 were also identified. Problems with body image relating to the stoma were experienced by 2 of 25 patients. CONCLUSION: The incidence of psychiatric disorder in patients embarking on transplantation is high and relates to their history of chronic illness. The additional stress of the transplantation operation and the long in-hospital rehabilitation period takes its toll on patients' emotional health and many acquire further psychiatric diagnoses. Managing the psychiatric health of patients is important for successful rehabilitation and their long-term health and wellbeing. PMID- 25131125 TI - Renal failure associated with intestinal transplantation: our experience in Spain. AB - BACKGROUND: Renal failure (RF) is a frequent complication in non-renal solid organ transplants. In the present study, we analyze our experience with intestinal transplants (ITx). METHODS: Between 2004 and 2012, we performed 21 ITx in 19 adult patients. Alemtuzumab was used as an induction agent followed by tacrolimus. Renal function was assessed before ITx and during the perioperative period. RESULTS: The main cause for transplants was non-resectable desmoids tumors (33.3%), followed by vascular thrombosis (19%) and others. Medical complications were frequent, especially infectious diseases, which were the most common (51%). Surgical complications were also frequent, but most of them (>50%) were mild but leading to a great number of re-operations and prolonged stays in hospital. Acute rejection is very frequent (66.6%) but mild in more than 70% of the cases. Finally, RF was very frequent (68.4%; 13/19 patients) and accounted for 15.6% of all medical complications. Causes were multiple. One patient is awaiting a kidney transplant, but no other patients need renal replacement therapy at the moment. Ileostomy closure was performed in 5 of 12 patients alive, showing improved renal function in 3 of them. CONCLUSIONS: RF is a problem in ITx and is always multifactorial. Increases in hospital stay, higher morbidity and is a cause for hospital readmission. Almost all patients had an impaired renal function when discharged. Immunosuppressants and ileostomy closure as soon as possible might prevent RF. PMID- 25131126 TI - The "Pavia model" of experimental small bowel transplantation in pigs: technical variations for ischemia reperfusion injury studies. AB - Ischemia reperfusion injury (IRI) is a major field of study in small bowel transplantation because of its implications regarding intestinal immunity. In this study, we have introduced some variations to the described models of IRI in pigs to make possible a complete isolation of the small bowel for IRI studies. In swine, two anatomical barriers make impossible a complete isolation of the small bowel at the origin of superior mesenteric artery (SMA) and vein (SMV): the main colic vessels, which originate distally to form SMA and SMV, and the blood supply of the distal portion of the duodenum and the cephalic part of the pancreas. In a group of Large White pigs (n = 5), we have performed a complete isolation of the small bowel, including sub-total colectomy and pancreaticoduodenectomy. Both SMA and SMV were isolated at the origin from the aorta and at the junction of the splenic vein, respectively. Intestinal continuity was restored with duodenojejunal anastomosis and with ileotransverse colon anastomosis. One pig died on postoperative day 5 from intestinal occlusion due to adhesions. The remaining four pigs were killed on postoperative day 7 after an uneventful postoperative course. No complications were found at autopsy. In swine, resection of part of the pancreas and duodenum and removal of the large bowel does not affect short-term survival, allowing a full isolation of the entire small bowel mimicking the transplantation procedure. Thus, this model appears to be attractive for IRI studies in the field of intestinal transplantation. PMID- 25131127 TI - Anti-inflammatory effects of ischemic preconditioning on rat small bowel allografts. AB - INTRODUCTION: Minimizing the inflammatory events that follow intestinal transplantation may influence immediate graft function and improve outcome. Ischemic preconditioning (IPc) has been shown to ameliorate early inflammatory responses, and it may also attenuate the potentially damaging inflammation after intestinal transplantation. Herein, we examine the influence of intestinal IPc on inflammatory indices (tissue expression of ICAM-1, CD11a, and CD44 and serum levels of the soluble ICAM-1, sICAM-1) after heterotopic intestinal transplantation. METHODS: Lewis rats received full-length preconditioned or non preconditioned Brown Norway intestinal allografts in the absence of immunosuppression. Preconditioned grafts were subjected to 1 cycle of 10 minutes of ischemia-reperfusion. Preconditioned and non-preconditioned isografts acted as controls. Blood was collected on alternate days post-transplant, and graft tissue harvested on sacrifice. ICAM-1, CD44, and CD11a expression was determined by immunohistochemistry, and the area of staining was quantified using image analysis. Serum soluble ICAM-1 levels were determined using an R&D Systems Quantikine enzyme immunoassay. RESULTS: (1) IPc ameliorated serum levels of sICAM 1 until severe rejection (day 7) overcame this down-regulation when compared to non-preconditioned allografts (day 3: 34,304 vs 40,479 pg/mL; day 5: 52,441 vs 61,593 pg/mL; day 7: 75,114 vs 73,309 pg/mL; day 9: 72,872 vs 76,314 pg/mL, respectively). (2) ICAM-1 expression was significantly lower in preconditioned allografts (1.02 vs 2.01 mm(2)). (3) CD44 tissue levels were also found to be lower in preconditioned allografts (0.86 vs 1.13 mm(2)). (4) There was a significant relationship between tissue ICAM-1 expression and serum levels of soluble ICAM-1 (P < .02). CONCLUSIONS: IPc improves inflammatory indices in the early stages following intestinal transplantation, and this might lead to a preserved cellular, architectural, and functional graft status. Furthermore, our results support the use of soluble ICAM-1 as a marker of endothelial activation, and thence of inflammation and developing rejection. PMID- 25131128 TI - Preface: The dawn of the new age. First experiences after being full member of Eurotransplant. AB - After so many years of the first initiative, to join the Eurotransplant (ET), this dream of many experts and professionals has become true. This difficult and long story was discussed in details and published here as the--prefaces of the 11(th) and 12(nd) Congresses of the Hungarian Transplantation Society. Since 1(st) July 2014 Hungary became a full member of ET. The 15(th) Congress was the first occasion to summarize the early experience of the membership. PMID- 25131129 TI - Early histopathological changes in new-onset diabetes after kidney transplantation. AB - BACKGROUND: New-onset diabetes after transplantation (NODAT) is one of the most common complications after kidney transplantation. METHODS: Patients were randomly assigned to receive cyclosporine A-based or tacrolimus-based immunosuppression. Fasting and oral glucose tolerance tests were performed, and the patients were assigned to one of the following 3 groups, on the basis of the results: normal, impaired fasting glucose/impaired glucose tolerance, or NODAT. NODAT developed in 14% of patients receiving cyclosporine A-based immunosuppression and in 26% of patients taking tacrolimus (P = .0002). RESULTS: Albumin levels were similar, but uric acid level (P = .002) and the age of the recipient (P = .003) were significantly different between the diabetic and the normal groups. Evaluation of tissue samples revealed that acute cellular rejection and interstitial fibrosis/tubular atrophy were significantly different in the NODAT group. Changes in the Banff score provided significant difference regarding tubulitis and interstitial inflammation (P = .05). CONCLUSIONS: The pathological effect of new-onset diabetes after kidney transplantation can be detected in the morphology of the renal allograft earlier, before the development of any sign of functional impairment. PMID- 25131130 TI - Prevalence of obesity and metabolic changes after kidney transplantation: Hungarian pediatric cohort study. AB - BACKGROUND: Cardiovascular mortality rate in patients with end-stage renal disease is 3 magnitudes higher than in the general population; it remains 10-fold higher after successful renal transplantation (Tx). Among others, obesity and hypertension can exert deleterious effects on vascular structure and function after Tx. Successful kidney transplantation may induce excessive weight gain in part because of the effects of steroid treatment. METHODS: The purpose of this study was to evaluate the presence of obesity in Tx children, their obesity related metabolic disturbances, and to assess their blood pressure and arterial stiffness in relation to obesity. Forty-one transplant children (age, 15.7 [3.5] years; 28 males) were studied. Body composition was assessed by body mass index (BMI), waist circumference, skin-fold measurements, and multifrequence bioimpedance analysis. Glucose metabolism, blood pressure, and arterial stiffness (with the use of pulse wave velocity) were studied. Age- and sex-dependent parameters were expressed as standard deviation scores (SDS). RESULTS: The prevalence of overweight (BMI >85%) increased from 3.2% to 24.4% at 49 months (3 183) (median, range); the BMI SDS increased from -0.27 (0.79) to 0.67 (1.35) after Tx. There was a close correlation between BMI SDS and the percentage of body fat and body fat mass in the Tx group (r = 0.80; r = 0.94, P = .0001). Children with disturbed glycemic control (n = 14) had higher percentage of body fat and higher blood pressure compared with those with normal glucose metabolism (P < .05). There was no difference in pulse wave velocity between the lean and obese patients. CONCLUSIONS: The prevalence of overweight or obese patients in the Hungarian pediatric renal cohort is low at transplantation and rises subsequently. Overweight is associated with disturbed glycemic control and increased blood pressure; however, these disturbances are not yet reflected by stiffening of the arteries. Strategies are needed to prevent obesity, its impact on hypertension, and cardiovascular disease in pediatric transplantation. PMID- 25131131 TI - De novo Prograf versus de novo Advagraf: are trough level profile curves similar? AB - BACKGROUND: According to the clinical trials, Advagraf (ADV) has efficacy and safety profile similar to Prograf (PROG). The aim of this study was to compare the graft functions, dosages, and tacrolimus (TAC) trough level profile curves of patients on de novo PROG and ADV therapy. METHODS: The ADV group included 39 de novo renal cases who had received initial immunosuppression (IS) with once-daily TAC (1 * 0.2 mg/kg from day1 after transplantation). We compared them with a PROG group of 38 transplant patients who received equivalent IS with twice-daily TAC (2 * 0.1 mg/kg from day1). In both groups, the IS was combined with antimetabolites and steroids. The mean follow-up time was similar (13.5 +/- 7 days) in both groups after renal transplantation until the emission of the patients from our clinic. RESULTS: TAC mean total daily dose was reduced and whole-blood trough levels decreased over the time in early postoperative days. Only on day 3 and day 4 after transplant, a significant higher adjustment in the ADV dosage was necessary to achieve sufficient TAC trough levels. The average TAC trough level profile curves were similar in PROG and ADV groups, but the individual curves were very different. Mainly in patients on ADV therapy, the initial concentrations were often >30 ng/mL, and in some cases on the 9th posttransplant day decreased to <5 ng/mL, then slowly increased into the required therapeutic range. CONCLUSIONS: The results demonstrate that patients after renal transplantation can be safely treated de novo with ADV. Setting the required therapeutic TAC blood levels may require more attention to avoid the "fluctuations" of trough level profile curve during the early postoperative period. Our data suggest that dose adjustment of ADV can be carried out more carefully compared with PROG on the basis of clinical symptoms and the value of TAC blood levels to avoid acute rejection and toxicity. PMID- 25131132 TI - Three-year longitudinal clinical trial of arterial function assessed by a oscillometric non-invasive method in comparison with carotid sclerosis and transferrin kidney-transplanted patients. AB - Chronic kidney disease remains one of the main risk factors of cardiovascular disease. However, patients with kidney transplantation have better life expectancy and better quality of life compared with patients on dialysis. In patients with a well-functioning graft, the main cause of death is cardiovascular in origin. Metabolic pathways have complex effects on arterial function that can be monitored by conventional ultrasonography and with the assessment of arterial stiffness by oscillometric non-invasive technique. Forty-one primer cadaver kidney-transplanted patient were involved in a 3-year longitudinal clinical trial (21 female, 20 male; average age, 40.16 +/- 12.56 years). Arterial stiffness parameters referring to rigidity of the arterial wall (pulse wave velocity [PWV], augmentation index, and pulse pressure) were investigated. Correlation between stiffness, and laboratory parameters (serum creatinine, urea, hemoglobin, albumin, cholesterine, triglycerides, transferrin, uric acid, glomerular filtration rate, and C-reactive protein) were analyzed. A non-invasive oscillometric method--Tensiomed Arteriograph--was applied to assess the arterial stiffness parameters. Statistical analysis was performed with the use of Statistica for Windows, version 8.0. A value of P < .05 was considered statistically significant for all statistical tests. We found a positive correlation between PWV and left ventricular wall thickness and a negative correlation between PWV and ejection fraction. We also found a positive significant correlation between serum level of transferrin and PWV. There was simultaneous significant progression concerning PWV and carotid artery sclerosis in a 3-year follow-up. There was no fatal cardiovascular event during the study period among our patients. All of our patients involved in this study are still alive. Our findings suggest that arterial stiffness monitoring is a reliable method to assess global cardiovascular risk among kidney-transplanted patients. The oscillometric method is convenient, fast, painless technique to monitor arterial function, which, in the case of pathological findings, proposes more frequent cardiovascular control. PMID- 25131133 TI - Endogenous thrombin potential and examination of a further 31 analytes in liver transplant candidates. AB - BACKGROUND: To predict the change in patient status and differentation of the basic diseases, endogenous thrombin potential (ETP), clinical chemistry, and coagulation variables were measured in liver transplant-listed patients with different etiologies. METHODS: Differences in values of ETP and analytes of 30 control persons and 164 cirrhotic patients were examined by means of binary logistic regression. The relationship between the analytes and ETP parameters were analyzed by means of Spearman correlation. The different etiologies of cirrhosises were studied by factor and discriminant analyses. Binary logistic regression was applied to forecast changes in clinical status. Survival analysis was carried out with the appropriate variable. RESULTS: International Normalized Ratio and activated partial thromboplastin time values were higher, whereas the area-under-the-curve values were lower in cirrhosis than in healthy subjects. A strong relationship was found only between the peak height and the anti-thrombin III (ATIII) values. In the factor analysis, 3 factors were found, which explained 81.6% of the total variance. Combination of aspartate aminotransferase and ATIII mostly separated the basic disease groups from each other in the discriminant analysis. From 35 variables, the lactate dehydrogenase (LDH) and ATIII have been suited for predicting the change in patient status. Eighty percent of patients with low ATIII and high LDH levels had deterioration of their clinical status. CONCLUSIONS: Our study demonstrated that the ETP parameters did not provide additional information compared with "conventional" coagulation tests in cirrhosis. On the basis of our study, LDH and ATIII appear to be promising analytes to assess the clinical status of patients with cirrhosis. In our opinion, the classification system of liver transplant-listed patients can be improved with their use. PMID- 25131134 TI - New-onset diabetes mellitus and the analysis of dipeptidyl-peptidase-4 after liver transplantation. AB - BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a common complication after orthotopic liver transplantation (OLT). The diabetogenic effect of hepatitis C virus (HCV) infection is well known. The aim of this study was to analyze the glucose homeostasis before and after OLT. The oral glucose tolerance test (OGTT) was carried out, and dipeptidyl-peptidase-4 (DPP-4) activity was measured. METHODS: The study period was from 2012 to 2014. We enrolled 49 non-diabetic patients from the waiting list (group A) and 21 patients after OLT (group B). Seven patients were monitored continuously both before and after OLT. According to our preoperative OGTT results, 13 patients in group A had newly diagnosed diabetes mellitus (group A/DM) and 11 had impaired glucose tolerance (group A/IGT). In 25 cases, normal glucose tolerance was diagnosed (group A/NGT). The calculated homeostasis model assessment insulin resistance (HOMA2-IR) values were both in group A/DM and-IGT higher compared with group A/NGT (2.42 +/- 0.81 vs 2 +/- 0.98 vs 1.28 +/- 0.67; P = .001). In the case of HCV infection (n = 14; 29%) DM and IGT were more frequent. RESULTS: Six patients in group B had NODAT. In 9 cases, IGT and in 6 cases NGT was detected. In the case of HCV infection (n = 9; 43%), DPP-4 levels were higher compared with that in patients with all other indications for OLT (15.5 +/- 5.2 vs 8.7 +/- 3.5; P = .008). We evaluated the same individuals before and after OLT (n = 7), and a decrease in beta-cell function was noted. CONCLUSIONS: Preoperative OGTT is an important and easy investigation to rule out glucose imbalance before OLT. The HOMA2 calculation can also be useful both in preoperative and postoperative risk assessment. In our results, DPP-4 activity is not specific for the type of glucose homeostasis imbalance, but, in HCV infection, it is higher. DPP-4 inhibitors can be effective in the therapy of NODAT, especially in HCV-infected patients. PMID- 25131135 TI - Effect of setting temperature on glucono-delta-lactone-induced gelation of silver carp surimi. AB - BACKGROUND: Setting temperature is important for heat-induced surimi gel formation. However, there is little information concerning setting temperature on the properties of glucono-delta-lactone (GDL)-induced surimi gel, which is considered a new preparation technique. RESULTS: The pH of surimi gel induced by 2% GDL was about 4.6, while the breaking force of GDL-induced surimi gel preheated at a temperature range of 35-50 degrees C was higher than that of heat induced surimi gel. The breaking force, deformation and whiteness of GDL-induced surimi gel were increased with increasing setting temperature from 30 to 45 degrees C, but water-holding capacity was decreased. When setting temperature was further increased to 50 degrees C, the textural properties were decreased, and myosin heavy chain (MHC) was degraded slightly. The data of protein subunits solubilized in various solvents revealed that MHC participated in the formation of GDL-induced surimi gel mainly through hydrophobic interactions. Furthermore, when GDL-induced surimi gel was preheated at 45 degrees C, a compact and fine fiber microstructure was observed by scanning electron microscopy. CONCLUSION: Setting treatment at the appropriate temperature could promote the formation of a fine, compact GDL-induced surimi gel network, resulting in improved textural properties. PMID- 25131136 TI - Lessons learned from mice and man: mimicking human allergy through mouse models. AB - The relevance of using mouse models to represent human allergic pathologies is still unclear. Recent studies suggest the limitations of using models as a standard for assessing immune response and tolerance mechanisms, as mouse models often do not sufficiently depict human atopic conditions. Allergy is a combination of aberrant responses to innocuous environmental agents and the subsequent TH2-mediated inflammatory responses. In this review, we will discuss current paradigms of allergy - specifically, TH2-mediated and IgE-associated immune responses - and current mouse models used to recreate these TH2-mediated pathologies. Our overall goal is to highlight discrepancies that exist between mice and men by examining the advantages and disadvantages of allergic mouse models with respect to the human allergic condition. PMID- 25131137 TI - Characterisation of tissue transglutaminase-reactive T cells from patients with coeliac disease and healthy controls. AB - Previous studies have shown evidence for T lymphocytes specific for tissue transglutaminase (tTG) in the periphery of coeliac disease (CD) patients. These cells could play a role in disease pathogenesis and may be involved in providing help for the production of anti-tTG autoantibodies. The objective of this study was to further investigate the presence of tTG-specific T cells in patients with treated and untreated CD, and normal controls. Positive proliferative responses to three different commercial tTG antigens were detected in all groups tested, occurring more frequently and at higher levels in untreated CD patients. The addition of antibodies to HLA-DQ and HLA-DR caused a significant reduction in the proliferative response to tTG. T cell lines specific for tTG and composed predominantly of CD4-positive T cells were generated from responsive CD and control individuals, and were found to produce large amounts of interferon-gamma, as well as interleukins 10, 17A, and 21. PMID- 25131138 TI - C-Myc participates in beta-catenin-mediated drug resistance in A549/DDP lung adenocarcinoma cells. AB - The aim of this study was to investigate c-Myc and beta-catenin-mediated drug resistance in A549/DDP lung adenocarcinoma cells. Cisplatin sensitivity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) toxicity assay. beta-Catenin and c-Myc protein expression following cisplatin treatment were determined using western blotting and immunofluorescence. Flow cytometry was performed to detect cell cycle and apoptosis in A549, A549/DDP, and c-Myc small interfering RNA (siRNA)-transfected A549/DDP cells before and after treatment with different doses of cisplatin. The median inhibitory concentration (IC50 ) in cisplatin-treated A549 and A549/DDP cells was 5.769 +/- 0.24 MUmol/L and 28.373 +/- 0.96 MUmol/L, respectively; the cisplatin resistance of A549 cells was about five times that of A549/DDP cells. Endogenous beta-catenin and c-Myc expression in A549/DDP cells were higher than that in A549 cells, and were upregulated in A549/DDP cells (p < 0.05) and downregulated in A549 cells after 48 h cisplatin treatment (p < 0.05). beta catenin localization transferred from membrane/cytoplasmic/nuclear to cytoplasmic/nuclear, and c-Myc localization transferred from cytoplasmic/nuclear to nuclear in both cell lines following cisplatin treatment. The rate of apoptosis increased in a dose-dependent manner with cisplatin. After 48-h transfection with c-myc siRNA, A549/DDP cells were blocked in the S phase, and G0/G1-phase cells increased. Simultaneously, the apoptotic rate was increased (p < 0.05) and the IC50 decreased significantly (p < 0.05). C-myc, the downstream target gene of beta-catenin, plays an important role in regulating cisplatin resistance in A549/DDP cells. C-Myc siRNA improved the sensitivity of A549/DDP cells to cisplatin. PMID- 25131139 TI - Effects on upper airway collapsibility of presence of a pharyngeal catheter. AB - Catheters that traverse the pharynx are often in place during clinical or research evaluations of upper airway function. The purpose of this study was to determine whether the presence of such catheters affects measures of upper airway collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and resistance upstream of the site of collapse Rus) were assessed in 24 propofol anaesthetized subjects (14 men) with and without a multi-sensor oesophageal catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were maintained constant throughout each study. Six subjects had polysomnography(PSG) defined obstructive sleep apnea (OSA) and 18 either did not have or were at low risk of OSA. Airway patency was maintained with positive airway pressure. At intervals, pressure was reduced by varying amounts to induce varying degrees of inspiratory flow limitation. The slope of the pressure flow relationship for flow limited breaths defined Rus. Pcrit was similar with the catheter in and out (-1.5 +/- 5.4 cmH2 O and -2.1 +/- 5.6 cmH2O, respectively, P = 0.14, n = 24). This remained the case both for those with PSG-defined OSA (3.9 +/- 2.2 cmH2O and 2.6 +/- 1.4 cmH2O, n = 6) and those at low risk/without OSA (-3.3 +/- 4.9 cmH2O and 3.7 +/- 5.6 cmH2O, respectively, n = 18). Rus was similar with the catheter in and out (20.0 +/- 12.3 cmH2O mL(-1) s(-1) and 16.8 +/- 10.1 cmH2O mL(-1) s(-1), P = 0.22, n = 24). In conclusion, the presence of a small catheter traversing the pharynx had no significant effect on upper airway collapsibility in these anaesthestized subjects, providing reassurance that such measures can be made reliably in their presence. PMID- 25131141 TI - Is essential fatty acid status in late pregnancy predictive of post-natal depression? AB - OBJECTIVE: We tested the hypothesis that abnormal levels of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) during late pregnancy are associated with antenatal and post-natal depression. METHOD: We interviewed a sample of more than 900 women in late pregnancy. We assessed whether they met criteria for depression on a standardized measure of post-natal depression [the Edinburgh Post-natal Depression Scale (EPDS)] and met DSM-IV criteria for major depression and/or were in receipt of antidepressant medication. Blood was collected at that time to generate data on nine PUFA variables. Sample members were re-interviewed post natally to determine depressive experience in the 3 months following the birth of their baby. RESULTS: Univariate associations were demonstrated between pre-natal depression categorized using DSM criteria and measures of blood fatty acids including total omega-3, the ratio of omega-6 to omega-3, docosahexaenoic acid (DHA) omega-3 and DHA plus eicosapentaenoic acid (EPA) omega-3. Such associations were not found post-natally, but different associations were quantified between EPDS-diagnosed depression and total omega-6, total omega-3 and EPA omega-3. In multivariate analyses, slight associations were maintained between EPDS and lower omega-3, lower EPA and higher omega-6 when neuroticism, stress during pregnancy, a lifetime episode of depression and older age were included in the analysis. CONCLUSION: Findings in such a large sample indicate that PUFA status in late pregnancy is only slightly linked with the risk of post-natal depression when depression was quantified by the EPDS. There were no associations between post natal depression diagnosed by DSM criteria and any fatty acid variables. PMID- 25131140 TI - Targeting of viral capsids to nuclear pores in a cell-free reconstitution system. AB - Many viruses deliver their genomes into the nucleoplasm for viral transcription and replication. Here, we describe a novel cell-free system to elucidate specific interactions between viruses and nuclear pore complexes (NPCs). Nuclei reconstituted in vitro from egg extracts of Xenopus laevis, an established biochemical system to decipher nuclear functions, were incubated with GFP-tagged capsids of herpes simplex virus, an alphaherpesvirus replicating in the nucleus. Capsid binding to NPCs was analyzed using fluorescence and field emission scanning electron microscopy. Tegument-free capsids or viral capsids exposing inner tegument proteins on their surface bound to nuclei, while capsids inactivated by a high-salt treatment or covered by inner and outer tegument showed less binding. There was little binding of the four different capsid types to nuclei lacking functional NPCs. This novel approach provides a powerful system to elucidate the molecular mechanisms that enable viral structures to engage with NPCs. Furthermore, this assay could be expanded to identify molecular cues triggering viral genome uncoating and nuclear import of viral genomes. PMID- 25131142 TI - Imported loiasis in Italy: an analysis of 100 cases. AB - BACKGROUND: loiasis is a neglected filariasis, affecting millions of individuals living in the rainforest areas of West and Central Africa. Aim of this study was to compare clinical and parasitological manifestations of loiasis between subjects born in endemic areas and expatriates/travelers. METHODS: we report clinical and parasitological manifestations of 100 patients with imported loiasis seen between 1993 and 2013 at the Center of Tropical Diseases, Negrar, Italy. RESULTS: among the 100 patients, 30 were African immigrants, 70 were Europeans (59 long-term expatriates and 11 travelers). Thirty-five patients (19 Africans and 16 Europeans) had positive microfilaremia. Calabar swellings were twice as frequent in Europeans (90%) than in Africans (46.7%), while a history of "eyeworm" was recorded in a higher proportion of Africans (43.3%) than in Europeans (17.4%). The median duration of exposure in the non-endemic group was also fairly long (14.6 years). Different drug regimens were used for treatment. CONCLUSIONS: we suggest that the differences between Africans and Europeans are more likely to be related to genetic differences, rather than to chronicity. Moreover the management of imported loiasis needs standardization. PMID- 25131143 TI - Anemia and thrombocytopenia in Plasmodium vivax malaria is not unusual in patients from endemic and non-endemic settings. PMID- 25131145 TI - Differential growth in estuarine and freshwater habitats indicated by plasma IGF1 concentrations and otolith chemistry in Dolly Varden Salvelinus malma. AB - This study employed a combination of otolith microchemistry to indicate the recent habitat use, and plasma concentrations of the hormone insulin-like growth factor 1 (IGF1) as an index of recent growth rate, to demonstrate differences in growth and habitat use by Dolly Varden Salvelinus malma occupying both freshwater and estuarine habitats in south-west Alaska. Extensive sampling in all habitats revealed that fish had higher IGF1 levels in estuarine compared to lake habitats throughout the summer, and that the growth rates in different habitats within the estuary varied seasonally. In addition, otolith microchemistry indicated differentiation in estuarine habitat use among individual S. malma throughout summer months. Although growth in the estuary was higher than in fresh water in nearly all sites and months, the benefits and use of the estuarine habitats varied on finer spatial scales. Therefore, this study further illustrates the diverse life histories of S. malma and indicates an evaluation of the benefits of marine waters needs to include sub-estuary scale habitat use. PMID- 25131144 TI - Prospective relations between family conflict and adolescent maladjustment: security in the family system as a mediating process. AB - Conflict in specific family systems (e.g., interparental, parent-child) has been implicated in the development of a host of adjustment problems in adolescence, but little is known about the impact of family conflict involving multiple family systems. Furthermore, questions remain about the effects of family conflict on symptoms of specific disorders and adjustment problems and the processes mediating these effects. The present study prospectively examines the impact of family conflict and emotional security about the family system on adolescent symptoms of specific disorders and adjustment problems, including the development of symptoms of anxiety, depression, conduct problems, and peer problems. Security in the family system was examined as a mediator of these relations. Participants included 295 mother-father-adolescent families (149 girls) participating across three annual time points (grades 7-9). Including auto-regressive controls for initial levels of emotional insecurity and multiple adjustment problems (T1), higher-order emotional insecurity about the family system (T2) mediated relations between T1 family conflict and T3 peer problems, anxiety, and depressive symptoms. Further analyses supported specific patterns of emotional security/insecurity (i.e., security, disengagement, preoccupation) as mediators between family conflict and specific domains of adolescent adjustment. Family conflict was thus found to prospectively predict the development of symptoms of multiple specific adjustment problems, including symptoms of depression, anxiety, conduct problems, and peer problems, by elevating in in adolescent's emotional insecurity about the family system. The clinical implications of these findings are considered. PMID- 25131146 TI - Relationships between facial temperature changes, end-exercise affect and during exercise changes in affect: a preliminary study. AB - The present study was performed as an evaluation of the relationships between changes in facial temperature and self-reported pleasure-displeasure during an acute aerobic exercise bout. Ninety-two students performed a 10-minute long session of cycle ergometry at 80-85% of age-predicted maximal heart rate. Using infrared thermography and a single-item measure of pleasure-displeasure (the Feeling Scale, FS), facial temperature and the FS score were sampled at the beginning (Min1:00) and at the end of the exercise session (Min9:00). Statistical analyses revealed that cheek (but not forehead) temperature was higher at the end of the exercise bout compared to Min1:00 (it increased by about 5%). Change in cheek temperature was negatively related to end-exercise affect (beta = -0.28, P < 0.001) and to during-exercise affective changes (beta = -0.35, P < 0.001). No significant relationship with forehead temperature was found. Some of the possible reasons for this differential effect as well as theoretical and practical implications of our findings are discussed. PMID- 25131147 TI - Revisiting the surface anatomy of the sciatic nerve in the gluteal region. AB - The surface anatomy of the sciatic nerve (SN) in the gluteal region is clinically important (e.g., intramuscular injection). Anatomy texts describe the nerve in relation to the posterior superior iliac spine (PSIS), ischial tuberosity (IT), and greater trochanter (GT) but descriptions are inconsistent. The surface anatomy of the SN was determined in relation to these bony landmarks using computed tomography (CT) scans in living adults. One hundred consecutive adult pelvic CT scans (36 females, mean age 76 years) were available for dual consensus analysis. A further 19 adults (9 females, mean age 74 years) underwent pelvic CT scans in both prone and supine positions. The surface projection of the SN along a line between the PSIS and IT and between the IT and GT was measured. The SN was identified in 95% of scans at a mean of 5.2 +/- 1.0 cm from the PSIS and 11.4 +/- 1.1 cm from the IT. The SN was a mean of 5.8 +/- 0.8 cm from the IT and 6.2 +/- 1.0 cm from the GT. There were no significant differences in mean positions of the nerve between sides and sexes. A small but clinically irrelevant difference in the surface marking of the SN was found between supine and prone positions with respect to the GT and IT but not in relation to the PSIS and IT. In living adults, the SN lies approximately one-third of the way along a line between the PSIS and IT and half way between the GT and IT. PMID- 25131148 TI - General, but not abdominal, overweight increases odds of asthma among Norwegian adolescents: the Young-HUNT study. AB - AIM: The aim of this analysis was to examine the association between asthma and general and abdominal weight status, defined by age- and sex-specific cut-offs for body mass index (BMI) and waist circumference (WC) in adolescents. METHODS: Participants aged 12-19 years in the Young-HUNT (YH) Study (YH1 1995-1997: n = 8222; YH3 2006-2008: n = 7403) completed self-administered questionnaires in school as part of a series of cross-sectional, population-based studies conducted in Nord-Trondelag, Norway. Weight, height and WC were measured. Adjusted odds ratios (ORs) and 95% Confidence Intervals (CI) for asthma, defined by self reported physician diagnosis, were calculated. Potential effect modifiers evaluated included sex and pubertal development status (PDS). RESULTS: Asthma was reported by 11.8% of the adolescents in YH1 and 17.0% in YH3. Asthma odds significantly increased for adolescents with general (OR = 1.33; 95%CI: 1.13, 1.56), but not abdominal, overweight and increased for adolescents with general (OR = 1.34; 95%CI: 1.02, 1.75) or abdominal obesity (OR = 1.36; 95%CI: 1.16, 1.60). Underweight had no association with asthma regardless of weight assessment type, and PDS did not meaningfully influence the associations between asthma and weight. CONCLUSION: Overweight and obesity both increased the odds of asthma in 12-19 year-old Norwegians. WC did not add further information to that already provided by BMI to improve our understanding of the association between asthma and weight. PMID- 25131149 TI - Effects of prolonged in vitro culture and cryopreservation on viability, DNA fragmentation, chromosome stability and ultrastructure of bovine cells from amniotic fluid and umbilical cord. AB - The objective of this work was to study cellular types that did not participated in the gastrulation process, amniotic fluid cells (AFCs) and umbilical cord cells (UCCs), in conditions of long-term culture and cryopreserved with different solutions. The AFCs and UCCs were used in a comparative study with ear fibroblast cells (EFCs) that were cultured in vitro until 20 cellular passages and cryopreserved in 10% dimethylsulphoxide (DMSO), 5% dimethyl formamide (DMF) and 7% glycerol (Gly) solutions. The cellular viability, ultrastructure, DNA fragmentation and chromosome stability were evaluated to determine the cellular type most resistant. In all cell types, it was possible to evaluate the AFCs until 15 passages and UCCs until 20 passages with different periods of cellular growth to reach the confluence phase. Solutions containing 10% DMSO ensured viability of 90.33 +/- 5.58%, 90.56 +/- 4.40% and 81.90 +/- 3.31%, respectively for EFCs, AFCs and UCCs, being significantly more efficient and with less variation than other cryoprotectant solutions. The AFCs were more sensitive to cryopreservation and presented low viability rate at the passage 20 (17.2 +/- 8.87%). There was no change in karyotype and nuclear fragmentation was low in all cellular passages studied. With the scanning electron analysis was possible the characterization of AFCs and UCCs in suspension. The three cellular types of cells presented different shapes and characteristics on the surface. The results demonstrate that bovine AFCs and UCCs can be isolated, cultured in vitro and cryopreserved in 10% DMSO, not causing damage to DNA and chromosomes. The UCCs were more resistant than AFCs in all aspects. PMID- 25131150 TI - Practical approach to prepare solid dispersion drug product using spherical silicate. AB - The purpose of this study is to establish a novel approach for preparing a solid dispersion drug product using spherical silicate by a Wurster-type fluidized bed granulator. The spherical silicate used in this study has porous structure and ideal particle size for loading by a Wurster-type fluidized bed granulator. As model drugs, ibuprofen (IBU), indomethacin (IMC), and phenytoin (PNT) were used and the proposed approach was applied to prepare amorphous drug. All drugs could be loaded on the spherical silicate in an amorphous state. On the other hand, spray drying of spherical silicate suspended in IBU solution was conducted to prepare amorphous product of IBU as a reference; however, complete amorphization was not achieved. Dissolution profiles of each drug after loading on spherical silicate by a Wurster-type fluidized bed granulator were evaluated, and dramatic improvement of dissolution was observed compared with those of crystalline drug. In the proposed approach, specific surface area and particle size of spherical silicate were determined as a key factors to contribute to high yield of amorphous product. PMID- 25131151 TI - Survival dynamics of tick-borne encephalitis virus in Ixodes ricinus ticks. AB - Biotic factors contributing to the survival of tick-borne viruses in nature are poorly understood. Using tick-borne encephalitis virus (TBEV) and its principal European vector, Ixodes ricinus, we examined the relative roles of salivary gland infection, co-feeding transmission, and moulting in virus survival. Virus titres in the salivary glands increased after blood-feeding in a time- and dose dependent manner. This was observed in ticks infected by inoculation but not in ticks infected by the natural route of co-feeding. Amplification of infection prevalence occurred via co-feeding. However, when larvae or nymphs subsequently moulted, the infection prevalence dramatically declined although this was not observed when ticks were infected by inoculation. Trans-stadial survival is a hitherto overlooked parameter that may contribute to the low incidence of TBEV infection in field-collected I. ricinus ticks. PMID- 25131153 TI - Affective neural networks and cognitive learning systems for big data analysis. PMID- 25131152 TI - Co-circulation of multiple species of Rickettsiales bacteria in one single species of hard ticks in Shenyang, China. AB - Bacteria in the order Rickettsiales include some of the most important zoonotic (re)emerging pathogens for animals and humans. In 2012, a total of 1267 adult Haemaphysalis longicornis ticks were collected from domestic animals (cattle and sheep) in Shenyang of Liaoning Province, China. These ticks were grouped into 181 pools (each pool with 6-7 ticks). Rickettsiales agents were identified in 93 (51.38%) tick pools using PCR targeting rrs (16S rRNA). In addition to 16S rRNA gene sequences, gltA and groEL gene sequences were also recovered from these positive samples. Phylogenetic analyses of these sequences revealed the presence of five species of Rickettsiales bacteria in a single tick species (H. longicornis) in nature in Shenyang, including Rickettsia japonica, Rickettsia raoultii, Anaplasma centrale, Anaplasma bovis, and a potentially novel A. phagocytophilum variant. Additionally, two Candidatus Ehrlichia spp. (Ehrlichia sp. Yonaguni138, Candidatus Ehrlichia shimanensis) were also identified in these ticks, with the highest prevalence of Ehrlichia sp. Yonaguni138 (73/181, 40.3%). Notably, these agents except the novel A. phagocytophilum variant had close evolutionary relationships with those previously identified in northeastern Asian countries including Korea, Japan, and Russia, indicating a geographic clustering pattern. Our data also reinforce the need for vigilance in recognition and prevention of rickettsiosis, ehrlichiosis, and anaplasmosis in humans and animals in this region. PMID- 25131154 TI - Perspectives on heterogeneous photochemistry. AB - Heterogeneous photochemistry has a potentially important role in production of energy, in environmental remediation and in sustainable production of chemicals. Photochemical efficiency depends on both materials properties and the desired chemical reaction that is promoted through creation of an excited state. A detailed understanding of the interplay between materials properties and reactivity requires a molecular-scale approach that determines the elementary steps in the overall process. This personal account summarizes the role of defects in determining the photochemical and thermal reactions on rutile titania, a model for semiconductor metal oxide photocatalysts that defects, e.g., Ti interstitials present in the subsurface region, and O adatoms on the surface, have a substantial impact on the efficiency for photochemical conversion through modification of molecular binding and also through likely modification of charge carrier dynamics. Design of materials must include engineering of the optical and electronic properties of the semiconductor photocatalyst, and understanding of the key photochemical steps involved in specific processes to ensure proper alignment of their electronic states with the band structure of the material. Thus, fundamental surface science studies and development of time-dependent theoretical methods that map out the reaction mechanism for photochemical processes on materials with controlled composition and structure are critical. PMID- 25131155 TI - Leptin receptor is expressed by epidermis and skin appendages in dog. AB - Leptin is a polypeptide secreted by adipocytes which binds to a specific receptor (Ob-R) that is expressed in various tissues. The wide distribution of the Ob-R suggests that leptin might exert diverse biological functions, not only by regulating energy metabolism and appetite, but also by acting as a mitogen in many cell types, including keratinocytes. In this study, the presence and localization of Ob-R was investigated in the skin of the dog using RT-PCR and immunohistochemical techniques. RT-PCR revealed the presence of Ob-R m-RNA in the skin specimens collected from the dorsal region of two smooth coat breed dogs. Through immunohistochemistry performed on the skin of five dogs, the expression of the receptor was observed in the basal layer of the epidermis, in the hair follicles as well as in the apocrine sweat and sebaceous glands. No staining for Ob-R was detected in the suprabasal epidermis layers. Strong positive signals were observed in many cells of the outer root sheath of hair follicles in growing and in regressive phases. The identification of Ob-R in the above targets suggests that leptin may play a role in the regulation of cyclic renewal of the epidermis and skin appendages in dog. This study represents an important contribution to understand the complex mechanisms that are involved in the skin biology in this species. PMID- 25131157 TI - Impact of Body Mass Index on Progression of IgA Nephropathy Among Japanese Patients. AB - BACKGROUND: The impact of being overweight remains unclear in Asian populations that tend to be lean. The objective of this study is to clarify the impact of body mass index (BMI) and metabolic factors on the prognosis of Japanese patients with IgA nephropathy (IgAN). METHODS: A total of 193 patients with IgAN were divided into three groups equally according to BMI: Group L (lean group, BMI: 15.6-20.1 kg/m(2) ), Group M (middle group, BMI: 20.2-23.0 kg/m(2) ), and Group O (obesity group, BMI: 23.1-31.9 kg/m(2) ). Clinical data at the time of renal biopsy and the progression of the patients after renal biopsy were analyzed. RESULTS: At the time of renal biopsy, hypertension, dyslipidemia, hyperuricemia, and hypercomplementemia in Group O were more significant compared with those in Group L and/or Group M. Uric acid, triglyceride, C3, C4, high-density lipoprotein cholesterol, serum creatinine, systolic blood pressure (BP), and diastolic BP were significantly correlated with BMI. In Group O, the remission of urinary protein over 5 years was significantly delayed using a log-rank test. At the final observation, the BMI of each group was as similar as that at renal biopsy. The patients with aggressive therapy, such as steroid therapy and/or tonsillectomy in Group O did not have major side effects, except for a slight elevation of total cholesterol and low-density lipoprotein cholesterol. CONCLUSION: Even slightly high BMI seems to be a risk factor for progress in Japanese patients with IgAN. PMID- 25131158 TI - Precise determination of the threshold diameter for a single-walled carbon nanotube to collapse. AB - Closed-edged bilayer graphene nanoribbons were formed by the spontaneous collapse of large-diameter single-walled carbon nanotubes (SWNTs) grown on gold nanoparticles by chemical vapor deposition. Such bilayer graphene nanoribbons could adopt different stacking configurations, such as AB-stacking or stacking order with any rotation angle, correlated with the chiral angles of their parent rounded SWNTs. On the basis of the electron diffraction characterizations on a good number of collapsed and uncollapsed SWNTs, the threshold diameter for SWNTs to collapse was precisely determined to be 5.1 nm, independent of the chiral angle of the SWNTs. The determination is consistent with that calculated by both classical adaptive intermolecular reactive empirical bond order force field and density functional theory after having taken the stacking effect and thermal fluctuation into account. PMID- 25131156 TI - Impact of a pharmacy benefit change on new use of mail order pharmacy among diabetes patients: the Diabetes Study of Northern California (DISTANCE). AB - OBJECTIVE: To assess the impact of a pharmacy benefit change on mail order pharmacy (MOP) uptake. DATA SOURCES/STUDY SETTING: Race-stratified, random sample of diabetes patients in an integrated health care delivery system. STUDY DESIGN: In this natural experiment, we studied the impact of a pharmacy benefit change that conditionally discounted medications if patients used MOP and prepaid two copayments. We compared MOP uptake among those exposed to the benefit change (n = 2,442) and the reference group with no benefit change (n = 8,148), and estimated differential MOP uptake across social strata using a difference-in-differences framework. DATA COLLECTION/EXTRACTION METHODS: Ascertained MOP uptake (initiation among previous nonusers). PRINCIPAL FINDINGS: Thirty percent of patients started using MOP after receiving the benefit change versus 9 percent uptake among the reference group (p < .0001). After adjustment, there was a 26 percentage point greater MOP uptake (benefit change effect). This benefit change effect was significantly smaller among patients with inadequate health literacy (15 percent less), limited English proficiency (14 percent less), and among Latinos and Asians (24 and 16 percent less compared to Caucasians). CONCLUSIONS: Conditionally discounting medications delivered by MOP effectively stimulated MOP uptake overall, but it unintentionally widened previously existing social gaps in MOP use because it stimulated less MOP uptake in vulnerable populations. PMID- 25131159 TI - Modification of a melanoma discrimination index derived from hyperspectral data: a clinical trial conducted in 2 centers between March 2011 and December 2013. AB - BACKGROUND: The morphology of pigmented skin lesions (PSLs) is predominantly a result of varying concentrations and distributions of pigmented molecules such as melanin and hemoglobin. Based on these differences and the fact that their information is contained in cutaneous spectra, a hyperspectral imager (HSI) for pigmented melanoma and a single discrimination index derived from the resultant hyperspectral data are proposed. OBJECTIVE: To develop and evaluate a new discrimination index for melanomas, compared to the previous index. METHODS: A HSI, which is convenient for both patients and clinicians, was newly developed and used in a clinical trial conducted in 2 centers with 80 patients with primary lesions and 17 volunteers between March 2011 and December 2013. There were 24 melanomas and 110 other PSLs. A previously proposed discrimination index was used without modifications. A new index, which emphasized the essential features of melanoma, was proposed, and its performance was examined. For each index, a threshold value was set to minimize the average value of the false positive and false negative fractions. The performances of both indices were compared. RESULTS: The sensitivity and specificity of the old index were 75% and 97%, respectively, while those of the new index were 96% and 87%. CONCLUSION: The new index had a higher sensitivity and adequate specificity, indicating that it is more useful than the old index. PMID- 25131160 TI - The immune pathogenesis of immune reconstitution inflammatory syndrome associated with highly active antiretroviral therapy in AIDS. AB - The present study investigated the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) in acquired immunodeficiency syndrome (AIDS) patients undergoing highly active antiretroviral therapy (HAART). A total of 238 patients with AIDS who received initial HAART were included in this prospective cohort study. Blood samples were collected immediately, at baseline, at week 12, and at week 24 after initial HAART and at the onset of IRIS. Lymphocyte subsets, Th1 and Th2 cytokines, and interleukin (IL)-7 levels were measured by flow cytometry or ELISA. Among the 238 patients with AIDS who received HAART, 47 patients developed IRIS. The percentages of CD4(+) and CD8(+) naive, memory, and activated cells exhibited no significant differences between AIDS patients with and without IRIS 24 weeks after initial HAART. The percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells was lower in IRIS patients than in non-IRIS patients before HAART, 12 weeks after HAART, 24 weeks after HAART, and at the onset of IRIS. IL-2 and interferon (IFN)-gamma levels were significantly higher at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. In contrast, IL-4 and IL-10 levels were significantly lower at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS patients. Plasma IL-7 decreased gradually with the progression of HAART. The level of IL-7 was higher in IRIS patients than in non-IRIS patients at all follow-up time points. An imbalance of Th1/Th2 cytokines, a consistently low CD(+)CD25(+)Fox3(+) percentage, and a high IL-7 level may be crucial in the pathogenesis of IRIS in AIDS patients who had received HAART. PMID- 25131161 TI - Psychogenic nonepileptic seizures: should we use response to AEDS as a red flag for the diagnosis? AB - PURPOSE: Lack of response to anti-epileptic drugs (AEDS) is considered a "red flag" pointing to a diagnosis of Psychogenic Nonepileptic Seizures (PNES). On the other hand, placebo effects are relevant in any medical condition with a complex psychosocial component. We aimed to evaluate the presence and frequency of a placebo response in patients with sole PNES and explore its impact on diagnostic delay. METHODS: We reviewed the medical records of 102 patients referred for video EEG monitoring and diagnosed with PNES. Patients with PNES and epilepsy were excluded. The response to AEDs was analyzed according to patients' reports and medical records. Patients were classified, according to the response to AEDs, in two groups: responders (patients achieving remission) and non-responders. Then, we compared the diagnostic delay from the first event to the final diagnosis between these groups. RESULTS: Forty-seven patients (79.7%) with sole PNES who were using AEDs were identified. Twenty-two patients (46.8%) had reported complete or partial remission of PNES with mean response duration of 7.2 months (SD+9.6 months). The time delay of the diagnosis in the AED responder group was 10.6 years; the delay in non-responders was 5.6 years (p=0.035). CONCLUSION: Patients with sole PNES receiving AEDs can go into PNES remission. A favorable response to AEDs is likely to be interpreted as supporting a diagnosis of epilepsy and is associated with diagnostic delay. Physicians should bear in mind that patients with PNES may be particularly vulnerable to placebo effects. PMID- 25131162 TI - Ehlers-Danlos syndrome: a cause of epilepsy and periventricular heterotopia. AB - PURPOSE: Ehlers-Danlos syndrome (EDS) comprises a variety of inherited connective tissue disorders that have been described in association with various neurological features. Until now the neurological symptoms have not been studied in detail; therefore, the aim of this review is to analyze the possible association between EDS, epilepsy and periventricular heterotopia (PH). METHODS: We have carried out a critical review of all cases of epilepsy in EDS patients with and without PH. RESULTS: Epilepsy is a frequent neurological manifestation of EDS; generally, it is characterized by focal seizures with temporo-parieto occipital auras and the most common EEG findings epileptiform discharges and slow intermittent rhythm with delta-theta waves. Epilepsy in EDS patients is usually responsive to common antiepileptic therapy; very few cases of drug resistant focal epilepsy requested surgical treatment, with favorable results in terms of outcome. Epilepsy is the most common presenting neurological manifestation associated with PH in EDS patients. Abnormal anatomic circuitries (including heterotopic nodules) could generate epilepsy in patients with PH. CONCLUSION: Among the principal neurological manifestations, epilepsy and PH have a considerable importance and can influence the long-term evolution of these patients. We hypothesize that PH may determine the epileptic manifestations in patients with EDS; much remains to be learnt about the relationships between nodules and the epileptic manifestations in EDS syndrome. PMID- 25131163 TI - Human Beta-papillomavirus infection and keratinocyte carcinomas. AB - Although the role of oncogenic human Alpha-papillomaviruses (HPVs) in the development of mucosal carcinomas at different body sites (eg cervix, anus, oropharynx) is fully recognized, a role for HPV in keratinocyte carcinomas (KCs; basal and squamous cell carcinomas) of the skin is not yet clear. KCs are the most common cancers in Caucasians, with the major risk factor being ultraviolet (UV) light exposure. A possible role for Beta-HPV types (BetaPV) in the development of KC was suggested several decades ago, supported by a number of epidemiological studies. Our current review summarizes the recent molecular and histopathological evidence in support of a causal association between BetaPV and the development of KC, and outlines the suspected synergistic effect of viral gene expression with UV radiation and immune suppression. Further insights into the molecular pathways and protein interactions used by BetaPV and the host cell is likely to extend our understanding of the role of BetaPV in KC. PMID- 25131164 TI - Pharmacokinetics of oral chlortetracycline in nonpregnant adult ewes. AB - The objectives of this study were to determine plasma concentrations and pharmacokinetic parameters of feed-grade chlortetracycline (CTC) in sheep after oral administration of 80 or 500 mg/head daily, divided into two equal doses given at 12-h intervals for 8 days. These are the approved, and commonly used but unapproved, feed additive doses, respectively, in the United States for the prevention of ovine infectious abortion. Blood samples were collected just prior to dosing at 0, 12, 24, 72, 96, and 192 h, as well as 4, 8, 12, 24, and 36 h after the last dose, and noncompartmental pharmacokinetic analysis was performed to estimate elimination half-life and area under the plasma concentration-time curve (AUC). Mean observed maximum CTC concentrations (Cmax ) were 20.0 ng/mL (80 mg dose) and 101 ng/mL (500 mg dose). Mean apparent elimination half-life was 18 h (80 mg dose) and 20 h (500 mg dose). Although published data do not exist to estimate plasma CTC concentrations necessary for the prevention of ovine infectious abortion, concentrations reached in our study suggest that either the FDA-approved and FDA-unapproved dosages are not high enough or that the pharmacodynamic parameter relating preventive dose to pathogen minimum inhibitory concentrations is yet to be determined. PMID- 25131166 TI - Transcatheter implantation of a newly designed aortic prosthesis in a patient with a mechanical mitral valve. PMID- 25131165 TI - Total arterial revascularization with internal thoracic and radial artery grafts in triple-vessel coronary artery disease is associated with improved survival. AB - OBJECTIVES: We sought to evaluate our experience with total arterial revascularization and compare it with the traditional approach of a single internal thoracic artery supplemented by saphenous veins. METHODS: From 1995 to 2010, 6059 patients with triple-vessel coronary artery disease underwent primary isolated coronary artery bypass grafting at 8 centers. A study cohort of 3774 patients was formed, with 2988 (79%) undergoing total arterial revascularization and 786 (21%) receiving only saphenous veins to supplement a single in situ internal thoracic artery. In the total arterial revascularization group, bilateral internal thoracic arteries were used in 1079 patients (36%) and at least 1 radial artery was used in 2916 patients (97%). Propensity score matching was used for risk adjustment. RESULTS: Patients undergoing total arterial revascularization were younger (65.0+/-10.4 years vs 71.3+/-7.9 years, P<.001) and less likely to have diabetes, cerebrovascular disease, recent myocardial infarction, and severe left ventricular impairment. At 15 years, patients who underwent total arterial revascularization experienced superior unadjusted survival (62%+/-1.1% vs 35%+/-1.9%, P<.001). Multivariable Cox regression in the entire study cohort showed the total arterial group had improved survival with a hazard ratio of 0.79 (95% confidence interval, 0.70-0.90; P<.001). After propensity score matching yielded 384 patient pairs, patients who underwent total arterial revascularization showed improved survival at 15 years than patients who underwent single arterial revascularization (54%+/-3.3% vs 41%+/-3.0%, P=.0004). CONCLUSIONS: This large multicenter study suggests that a strategy of total arterial revascularization is associated with improved long-term survival compared with the use of only a single arterial and saphenous vein grafts. Total arterial revascularization should be encouraged in patients with a reasonable life expectancy. PMID- 25131167 TI - Usefulness of bridging thoracic endovascular aortic repair and sac irrigation followed by open repair in patients with mycotic thoracic aortic aneurysms. PMID- 25131168 TI - Skeletal muscle and plasma concentrations of cefazolin during cardiac surgery in infants. AB - OBJECTIVE: To describe the pharmacokinetics and tissue disposition of prophylactic cefazolin into skeletal muscle in a pediatric population undergoing cardiac surgery. METHODS: The subjects included 12 children, with a median age of 146 days (interquartile range, 136-174) and median weight of 5.5 kg (interquartile range, 5.2-7.3) undergoing cardiac surgery and requiring cardiopulmonary bypass with or without deep hypothermic circulatory arrest. Institutional cefazolin at standard doses of 25 mg/kg before incision and 25 mg/kg in the bypass prime solution were administered. Serial plasma and skeletal muscle microdialysis samples were obtained intraoperatively and the unbound cefazolin concentrations measured. Noncompartmental pharmacokinetic analyses were performed and the tissue disposition evaluated. RESULTS: After the first dose of cefazolin, the skeletal muscle concentrations peaked at a median microdialysis collection interval of 30 to 38.5 minutes. After the second dose, the peak concentrations were delayed a median of 94 minutes in subjects undergoing deep hypothermic circulatory arrest. Skeletal muscle exposure to cefazolin measured by the area under concentration time curve 0-last measurement was less in the subjects who underwent deep hypothermic circulatory arrest than in those who received cardiopulmonary bypass alone (P = .04). The skeletal muscle concentrations of cefazolin exceeded the goal concentrations for methicillin sensitive Staphylococcus aureus prophylaxis; however, the goal concentrations for gram-negative pathogens associated with surgical site infections were achieved only 42.1% to 84.2% and 0% to 11.2% of the intraoperative time in subjects undergoing cardiopulmonary bypass alone or deep hypothermic circulatory arrest, respectively. CONCLUSIONS: This cefazolin dosing strategy resulted in skeletal muscle concentrations that are likely not effective for surgical prophylaxis against gram-negative pathogens but are effective against methicillin-sensitive S aureus in infants undergoing cardiac surgery. PMID- 25131169 TI - The CarboMedics supra-annular Top Hat valve improves long-term left ventricular mass regression. AB - OBJECTIVE: The present study aimed to identify potential differences in hemodynamic performance between the supra-annular CarboMedics Top Hat valve and the intra-annular CarboMedics standard valve in terms of the long-term left ventricular mass reduction and transvalvular gradients. METHODS: We retrospectively reviewed a series of 186 consecutive patients who had undergone aortic valve replacement with a small size mechanical prosthesis at our institution from 2003 to 2013, receiving either a CarboMedics Top Hat valve (53 patients, valve size, 21 mm in 52.8% and 23 mm in 47.2%) or a CarboMedics standard prosthesis (133 patients, valve size, 19 mm in 14.3% and 21 mm in 85.7%). RESULTS: The in-hospital mortality was 9.4% and 11.3% in the Top Hat and standard groups, respectively (P = .71). The mean percentage of left ventricular mass reduction was greater in the Top Hat group (33% +/- 15.8% vs 20.1% +/- 16.6%, P < .001). The mean postoperative peak aortic gradient was lower in the Top Hat group (19.9 +/- 8.9 vs 29.6 +/- 8.6 mm Hg; P < .001). Spearman analysis showed a positive correlation between the indexed effective orifice area and the percentage of left ventricular mass reduction (Rho = +0.65, P = .02). The survival in the Top Hat group was 79.7% and 71.7% at 5 and 10 years, respectively. In the standard group, survival was 66.8% and 61.5% at 5 and 10 years, respectively (log-rank test, 0.19). Cox regression demonstrated severe myocardial hypertrophy (hazard ratio, 2.559; 95% confidence interval, 1.095 5.981) as one of the independent predictors of survival. CONCLUSIONS: The Top Hat valve surpasses hemodynamically the intra-annular valve. We suggest the supra annular Top Hat prosthesis can be especially recommended for patients with a small aortic root and severe myocardial hypertrophy. PMID- 25131171 TI - A simple approach to mitral valve repair: posterior leaflet height adjustment using a partial fold of the free edge. AB - OBJECTIVES: Multiple techniques have been used to repair degenerative mitral valve prolapse with leaflet elongation, without creating systolic anterior motion. We describe a simple, reproducible, measured technique to guide repair. METHODS: From January 2010 to July 2012, 171 patients underwent mitral valve repair; 128 (75%) with Carpentier type II prolapse. For 48 patients (37.5%), the resected posterior leaflet free edge was partially folded to restore the normal 2:1 ratio of the A2 and P2. All patients underwent complete ring annuloplasty sized to the height of A2. RESULTS: The preoperative A2/P2 ratio was 1.5 +/- 0.5. After repair, the A2/P2 ratio was 1.9 +/- 0.3 and 2.0 +/- 0.3 in the no fold and partial fold groups, respectively (P = .57). The ring sizes were larger in the partial fold group (P < .001) because the A2 height was larger (P = .001). No obstructive systolic anterior motion was present. Of the 171 patients, 91.4% had grade 4+ preoperative mitral regurgitation, with no 3 or 4+ mitral regurgitation during follow-up. At the last follow-up visit, grade 2+ mitral regurgitation was observed in 5% of the patients. No 30-day mortalities or reoperations occurred. CONCLUSIONS: Partial fold of the posterior leaflet free edge is a simple technique to restore the normal 2:1 ratio of A2/P2 with a ring size determined by the A2 height. Using just the A2 height, mitral surgeons can reproducibly repair the posterior leaflet prolapse, choose the appropriate ring size, and avoid more complex leaflet reconstruction or judgment of the neochord length. PMID- 25131172 TI - New technique for passage of endograft through problematic arch anatomy. PMID- 25131173 TI - Expanded level of sympathetic chain removal does not increase the incidence or severity of compensatory hyperhidrosis after endoscopic thoracic sympathectomy. AB - OBJECTIVE: Compensatory hyperhidrosis is a common devastating adverse effect after endoscopic thoracic sympathectomy for patients undergoing surgical treatment of primary hyperhidrosis. We sought to determine whether a correlation existed in our patient population between the level and extent of sympathetic chain resection and the subsequent development of compensatory hyperhidrosis. METHODS: All patients undergoing endoscopic thoracic sympathectomy in the T2-T3, T2-T4, T2-T5, or T2-T6 levels for palmar or axillary hyperhidrosis at the University of Iowa Hospital and Clinics (n = 97) from January 2004 to January 2013 were retrospectively reviewed. RESULTS: Differences in the preoperative patient characteristics were not statistically significant among the patients receiving T2-T3, T2-T4, T2-T5, or T2-T6 level resections. Of the 97 included patients, 28 (29%) experienced transient compensatory hyperhidrosis and 4 (4%) complained of severe compensatory hyperhidrosis and required additional treatment. No operative mortalities occurred, and the morbidity was similar among the groups. CONCLUSIONS: Most patients had successful outcomes after undergoing extensive resection without changes in the incidence of compensatory hyperhidrosis. Therefore, we recommend performing complete and adequate resection for relief of symptoms in patients with primary hyperhidrosis. PMID- 25131174 TI - Surgical repair of descending thoracic and thoracoabdominal aortic aneurysm involving the distal arch: open proximal anastomosis under deep hypothermia versus arch clamping technique. AB - BACKGROUND: Surgical repair of a descending thoracic and thoracoabdominal aortic aneurysm (DTA/TAAA) involving the distal arch is challenging and requires either deep hypothermic circulatory arrest (DHCA) or crossclamping of the distal arch. The aim of this study was to compare these 2 techniques in the treatment of DTA/TAAA involving the distal arch. METHODS: From 1994 to 2012, 298 patients underwent open repair of DTA/TAAA through a left thoracotomy. One hundred seventy four patients with distal arch involvement who were suitable for either DHCA (n=81) or arch clamping (AC; n=93), were analyzed. In-hospital outcomes were compared using propensity scores and inverse-probability-of-treatment weighting adjustment to reduce treatment selection bias. RESULTS: Early mortality was 11.1% in the DHCA group and 8.6% in the AC group (P=.58). Major adverse outcomes included stroke in 16 patients (9.2%), low cardiac output syndrome in 15 (8.6%), paraplegia in 10 (5.7%), and multiorgan failure in 10 (5.7%). After adjustment, patients who underwent DHCA were at similar risk of death (odds ratio [OR], 1.14; P=.80) and permanent neurologic injury (OR, 0.95; P=.92) to those who underwent AC. Although prolonged ventilator support (>24 hours) was more frequent with DHCA than with AC (OR, 2.60; P=.003), DHCA showed a tendency to lower the risk of paraplegia (OR, 0.15; P=.057). CONCLUSIONS: Compared with AC, DHCA did not increase postoperative mortality and morbidity, except for prolonged ventilator support. However, DHCA may offer superior spinal cord protection to AC during repair of DTA/TAAA involving the distal arch. PMID- 25131175 TI - Echo-acoustic flow dynamically modifies the cortical map of target range in bats. AB - Echolocating bats use the delay between their sonar emissions and the reflected echoes to measure target range, a crucial parameter for avoiding collisions or capturing prey. In many bat species, target range is represented as an orderly organized map of echo delay in the auditory cortex. Here we show that the map of target range in bats is dynamically modified by the continuously changing flow of acoustic information perceived during flight ('echo-acoustic flow'). Combining dynamic acoustic stimulation in virtual space with extracellular recordings, we found that neurons in the auditory cortex of the bat Phyllostomus discolor encode echo-acoustic flow information on the geometric relation between targets and the bat's flight trajectory, rather than echo delay per se. Specifically, the cortical representation of close-range targets is enlarged when the lateral passing distance of the target decreases. This flow-dependent enlargement of target representation may trigger adaptive behaviours such as vocal control or flight manoeuvres. PMID- 25131176 TI - A new target for the old regulator: H-NS suppress T6SS secretory protein EvpP, the major virulence factor in the fish pathogen Edwardsiella tarda. AB - The evpP gene in fish pathogen Edwardsiella tarda, coding the T6SS secretory protein EvpP and carrying an evpA-evpO independent promoter region, was crucial for host cell invasion. The transcription of evpP was positively regulated by either the two-component system EsrA-EsrB or iron concentration, and its overexpression was known to enhance the invasion ability in our previous study. This work demonstrated that the H-NS protein, a pleiotropic regulator of gene expression, was a new transcriptional modulator of evpP gene. The results showed that in vivo the transcriptional level of evpP was downregulated by H-NS and in vitro this global regulator interacted directly with evpP promoter region. Moreover, DNase I footprinting experiments mapping the interaction regions of H NS and evpP revealed that this global regulator bound to evpP promoter and neighbouring areas at multiple sites. We provided a new insight into evpP regulation network and demonstrated the repression of H-NS to the transcription of evpP gene. SIGNIFICANCE AND IMPACT OF THE STUDY: Recently, the devastating fish disease edwardsiellosis caused by Edwardsiella tarda has been widely concerned. The xenogeneic silencing of the classic regulator H-NS to the T6SS secretory protein EvpP, which played an important role in the virulence of Edw. tarda, was firstly reported in this study. It raised a better understanding of the virulence regulation of EvpP and provided more information about the complex infection mechanism of this pathogen. Our findings would contribute to the development of live attenuated vaccines against edwardsiellosis thus reducing the economic losses caused by this bacterium. PMID- 25131178 TI - Edge effects on moisture reduce wood decomposition rate in a temperate forest. AB - Forests around the world are increasingly fragmented, and edge effects on forest microclimates have the potential to affect ecosystem functions such as carbon and nutrient cycling. Edges tend to be drier and warmer due to the effects of insolation, wind, and evapotranspiration and these gradients can penetrate hundreds of metres into the forest. Litter decomposition is a key component of the carbon cycle, which is largely controlled by saprotrophic fungi that respond to variation in temperature and moisture. However, the impact of forest fragmentation on litter decay is poorly understood. Here, we investigate edge effects on the decay of wood in a temperate forest using an experimental approach, whereby mass loss in wood blocks placed along 100 m transects from the forest edge to core was monitored over 2 years. Decomposition rate increased with distance from the edge, and was correlated with increasing humidity and moisture content of the decaying wood, such that the decay constant at 100 m was nearly twice that at the edge. Mean air temperature decreased slightly with distance from the edge. The variation in decay constant due to edge effects was larger than that expected from any reasonable estimates of climatic variation, based on a published regional model. We modelled the influence of edge effects on the decay constant at the landscape scale using functions for forest area within different distances from edge across the UK. We found that taking edge effects into account would decrease the decay rate by nearly one quarter, compared with estimates that assumed no edge effect. PMID- 25131179 TI - The consequences of contracting early and often. PMID- 25131177 TI - Quantification of in vivo colonic motor patterns in healthy humans before and after a meal revealed by high-resolution fiber-optic manometry. AB - BACKGROUND: Until recently, investigations of the normal patterns of motility of the healthy human colon have been limited by the resolution of in vivo recording techniques. METHODS: We have used a new, high-resolution fiber-optic manometry system (72 sensors at 1-cm intervals) to record motor activity from colon in 10 healthy human subjects. KEY RESULTS: In the fasted colon, on the basis of rate and extent of propagation, four types of propagating motor pattern could be identified: (i) cyclic motor patterns (at 2-6/min); (ii) short single motor patterns; (iii) long single motor patterns; and (iv) occasional retrograde, slow motor patterns. For the most part, the cyclic and short single motor patterns propagated in a retrograde direction. Following a 700 kCal meal, a fifth motor pattern appeared; high-amplitude propagating sequences (HAPS) and there was large increase in retrograde cyclic motor patterns (5.6 +/- 5.4/2 h vs 34.7 + 19.8/2 h; p < 0.001). The duration and amplitude of individual pressure events were significantly correlated. Discriminant and multivariate analysis of duration, gradient, and amplitude of the pressure events that made up propagating motor patterns distinguished clearly two types of pressure events: those belonging to HAPS and those belonging to all other propagating motor patterns. CONCLUSIONS & INFERENCES: This work provides the first comprehensive description of colonic motor patterns recorded by high-resolution manometry and demonstrates an abundance of retrograde propagating motor patterns. The propagating motor patterns appear to be generated by two independent sources, potentially indicating their neurogenic or myogenic origin. PMID- 25131180 TI - Delayed QRS transition in the precordial leads of an electrocardiogram as a predictor of sudden cardiac death in the general population. AB - BACKGROUND: QRS transition zone is related to the electrical axis of the heart in the horizontal plane and is easily determined from the precordial leads of a standard 12-lead ECG. However, whether delayed QRS transition, or clockwise rotation of the heart, carries prognostic implications and predicts sudden cardiac death (SCD) is unclear. OBJECTIVE: The purpose of this study was to study whether delayed transition is associated with mortality and SCD. METHODS: We evaluated 12-lead ECGs of 10,815 Finnish middle-aged subjects from the general population (52% men, mean age 44 +/- 8.5 years) and followed them for 30 +/- 11 years. Main end-points were mortality and SCD. RESULTS: Delayed QRS transition at lead V4 or later occurred in 1770 subjects (16.4%) and markedly delayed transition at lead V5 or later in 146 subjects (1.3%). Delayed transition zone was associated with older age, male gender, higher body mass index, hypertension, baseline cardiovascular disease, leftward shift of the frontal QRS axis, wider QRS-T angle, and ECG left ventricular hypertrophy. After adjusting for several clinical and ECG variables, delayed transition was associated with overall mortality (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.07-1.22, P < .001) and SCD (HR 1.23, 95% CI 1.03-1.47, P = .029). Markedly delayed transition at V5 or later predicted significantly SCD (HR 1.89, 95% CI 1.18-3.03, P = .008) and all-cause mortality (HR 1.30, 95% CI 1.07-1.58, P = .01). However, further adjustments for repolarization abnormalities attenuated this effect. CONCLUSION: Delayed QRS transition in the precordial leads of an ECG seems to be a novel ECG risk marker for SCD. In particular, markedly delayed transition was associated with significantly increased risk of SCD, independent of confounding factors. PMID- 25131181 TI - [Familial combined hyperlipidemia: consensus document]. AB - Familial combined hyperlipidemia (FCH) is a frequent disorder associated with premature coronary artery disease. It is transmitted in an autosomal dominant manner, although there is not a unique gene involved. The diagnosis is performed using clinical criteria, and variability in lipid phenotype and family history of hyperlipidemia are necessaries. Frequently, the disorder is associated with type2 diabetes mellitus, arterial hypertension and central obesity. Patients with FCH are considered as high cardiovascular risk and the lipid target is an LDL cholesterol <100mg/dL, and <70mg/dL if cardiovascular disease or type 2 diabetes are present. Patients with FCH require lipid lowering treatment using potent statins and sometimes, combined lipid-lowering treatment. Identification and management of other cardiovascular risk factors as type 2 diabetes and hypertension are fundamental to reduce cardiovascular disease burden. This document gives recommendations for the diagnosis and global treatment of patients with FCH directed to specialists and general practitioners. PMID- 25131182 TI - Myelosuppression toxicity of palliative splenic irradiation in myelofibrosis and malignant lymphoma. AB - OBJECTIVES: Distinctive splenomegaly resulting from extramedullary hematopoiesis and infiltration of neoplastic cells is observed in some patients with myelofibrosis (MF) or malignant lymphoma. Palliative splenic irradiation is known to be effective for such patients and is widely performed. However, little is known about the biological mechanism of palliative splenic irradiation. Various reports have focused on irradiation doses, in terms of efficacy and safety. We examined the toxicity of myelosuppression and the timing of the platelet, white blood cell, and red blood cell count nadirs within 3 months after the start of irradiation in a total of eight patients with MF or malignant lymphoma, all of whom underwent palliative splenic irradiation at our hospital between 2004 and 2013. METHODS: Five patients with idiopathic MF and three patients with non Hodgkin's lymphoma (NHL) treated with splenic irradiation between 2004 and 2013. Of the three patients with NHL, two had diffuse large B-cell lymphoma and one had mantle cell lymphoma. There were four male and four female patients, with median age of 61 years (range, 51-73). Patients with MF received irradiation at 20-100 cGy per fraction dose; four patients received irradiation five times a week and one patient received irradiation three times a week. In three of these patients, the irradiation dose was gradually increased while observing for hematotoxicity. Patients with NHL received irradiation at a fraction dose of 150-200 cGy, and all received irradiation five times a week. Irradiation was terminated when we judged symptoms to be alleviated, splenomegaly reduced, or efficacy to be poor. With regard to the total irradiation dose, 175, 320, 400, 600, and 640 cGy were given to one MF patient each, and 1050 and 3000 cGy were given to one and two NHL patients, respectively. RESULTS: Symptoms diminished or disappeared in five of the six symptomatic patients (83%). A reduction in the size of the spleen was confirmed in five of six patients (83%) with splenomegaly. For MF, the platelet count nadir was observed at week 3 in two patients, week 5 in two, and week 6 in one patient. For NHL, it was observed at week 1 in one patient, week 4 in one, and week 9 in one patient. For MF, the white blood cell count nadir was observed in at week 2 in one patient, week 3 in two, and week 5 in two patients. For NHL, it was observed at week 1 in one patient and week 4 in two patients. For MF, the red blood cell count nadir was observed at week 1 in two patients, week 3 in one, week 7 in one, and week 8 in one patient. For NHL patients, it was observed at week 1 in one patient, week 4 in one, and week 9 in one patient. Discussion There was a trend for the nadir to be steeper in patients with MF than in those with NHL. With regard to the total dose, symptoms diminished at the minimum dose of 175 cGy in MF patients, whereas the maximum dose of 3000 cGy was not effective in NHL patients. These observations suggest that a splenic lesion in NHL patients may be the primary site of neoplastic cell infiltration and that extramedullary hematopoiesis may not necessarily occur in the spleen. CONCLUSION: Although palliative irradiation of splenic lesions in patients with MF or NHL is safe and effective, optimal irradiation doses may differ for MF and NHL. More cases need to be accumulated to elucidate these differences. PMID- 25131183 TI - Targeting Th17 cells in autoimmune diseases. AB - T helper 17 (Th17) cells have been implicated in the pathogenesis of most common autoimmune diseases, including psoriasis, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). Although anti-interleukin-17 (IL-17) antibodies show marked clinical efficacy in psoriasis, targeting IL-17 alone is not sufficient to improve clinical end points in other autoimmune conditions, namely RA and Crohn's disease. Given that Th17 cells express IL-17 together with many other proinflammatory cytokines [IL-17F, IL-22, IL-26, and granulocyte-macrophage colony-stimulating factor (GM-CSF)], targeting the Th17 cell lineage may be superior to blocking a single effector cytokine. Here, we discuss the rationale for targeting two checkpoints in the development and inflammatory function of Th17 cells, retinoid-related orphan receptor-gammat (RORgammat) and IL-23, and we review recent progress in the development of both RORgammat small molecule inhibitors and IL-23 neutralizing antibodies. PMID- 25131184 TI - Factors influencing prostate-specific antigen response among men treated with testosterone therapy for 6 months. AB - INTRODUCTION: Factors influencing prostate-specific antigen (PSA) changes in men undergoing testosterone (T) therapy have not been well studied. AIM: The aim of this study was to assess the influence of selected variables on PSA changes in hypogonadal men administered with 1.62% testosterone gel (T-gel) for 6 months. METHODS: A double-blind, placebo-controlled study of 274 (234 T-gel, 40 placebo) hypogonadal men >18 years of age, with baseline T concentrations <300 ng/dL, PSA <=2.5 ng/mL, and negative digital rectal examination. Subjects received once daily T-gel for T therapy. MAIN OUTCOME MEASURES: Changes in mean serum PSA, percentage of free PSA (%fPSA), and T from baseline to 6 months (182 days). RESULTS: Mean age was 53.5 years and baseline mean values were total T 247 ng/dL, PSA 0.9 ng/mL, and %fPSA 24.6%. Among men treated with T-gel, T increased to 499 ng/dL and PSA increased by 0.1 ng/mL (P = 0.0012). PSA increased >=0.3 ng/mL in 26.3%, <0.3 ng/mL in 73.7%, including a decline from baseline in 33.0%. In the placebo group, T increased 29 ng/dL to 274 ng/dL, and PSA decreased 0.1 ng/mL, compared with baseline. A greater increase in PSA was noted in men >=60 years old than in men <60 years old (0.4 vs. 0.05 ng/mL, respectively; P = 0.0006). Mean PSA did not change in men with baseline serum T >250 ng/dL, whereas it increased by 0.2 ng/mL in men with T <=250 ng/dL (P = 0.0031). PSA increased 0.3 ng/mL in men with baseline %fPSA <20% and 0.1 ng/mL in men with %fPSA >=20%. CONCLUSIONS: Overall, T-gel treatment was associated with a minor increase in PSA, of questionable clinical significance. Factors predicting greater PSA increases included age >=60 years, baseline T <=250 ng/dL, and %fPSA <20%. Men with T >250 ng/dL and age <60 years demonstrated minimal or no PSA change. PMID- 25131185 TI - Surface confined heteroleptic copper(II)-polypyridyl complexes for photonuclease activity. AB - Heteroleptic copper(II)-polypyridyl complexes with extended pi-conjugated, aromatic terminal units were immobilized on glass/Si substrates to intercalate DNA and cleave it upon photoexposure. Photonuclease activity is shown to be high, well reproducible and non-destructible towards the assembled complexes. PMID- 25131186 TI - The Research Launchpad: measuring the efficiency and effectiveness of CTSA resource and service provision. PMID- 25131187 TI - In-vitro bipolar nano- and microsecond electro-pulse bursts for irreversible electroporation therapies. AB - Under the influence of external electric fields, cells experience a rapid potential buildup across the cell membrane. Above a critical threshold of electric field strength, permanent cell damage can occur, resulting in cell death. Typical investigations of electroporation effects focus on two distinct regimes. The first uses sub-microsecond duration, high field strength pulses while the second uses longer (50 MUs+) duration, but lower field strength pulses. Here we investigate the effects of pulses between these two extremes. The charging behavior of the cell membrane and nuclear envelope is evaluated numerically in response to bipolar pulses between 250 ns and 50 MUs. Typical irreversible electroporation protocols expose cells to 90 monopolar pulses, each 100 MUs in duration with a 1 second inter-pulse delay. Here, we replace each monopolar waveform with a burst of alternating polarity pulses, while keeping the total energized time (100 MUs), burst number (80), and inter-burst delay (1s) the same. We show that these bursts result in instantaneous and delayed cell death mechanisms and that there exists an inverse relationship between pulse-width and toxicity despite the delivery of equal quantities of energy. At 1500 V/cm only treatments with bursts containing 50 MUs pulses (2*) resulted in viability below 10%. At 4000 V/cm, bursts with 1 MUs (100*), 2 MUs (50*), 5 MUs (20*), 10 MUs (10*), and 50 MUs (2*) duration pulses reduced viability below 10% while bursts with 500 ns (200*) and 250 ns (400*) pulses resulted in viabilities of 31% and 92%, respectively. PMID- 25131188 TI - No impact of endogenous prothrombotic conditions on the risk of central venous line-related thrombotic events in children: results of the KIDCAT study (KIDs with Catheter Associated Thrombosis). AB - BACKGROUND AND OBJECTIVE: Central venous lines (CVLs) are the major exogenous risk factor for deep venous thrombosis (DVT) in children. The study objective was to assess whether endogenous prothrombotic conditions contribute to the risk of CVL-related DVT in children. METHODS: This was a cohort study of consecutive children with heart disease requiring CVLs for perioperative care. CVLs were inserted percutaneously in the upper venous system and patients received prophylaxis with continuous unfractionated heparin (50 u kg(-1) d(-1) ). Blood samples to test for prothrombotic conditions were collected prospectively and assayed in a blinded fashion. Outcome assessment was by screening for DVT by venography, venous ultrasound and echocardiography. RESULTS: The study population consisted of 90 children, median age 2.7 years (0 months-18 years). Prevalence rates of antithrombin deficiency, protein C deficiency, protein S deficiency, heterozygous factor V Leiden, prothrombin G20210A mutation, methylentetrahydrofolate C677TT genotype, hyperhomocysteinemia, lupus anticoagulant, anticardiolipin antibodies and increased levels of lipoprotein (a) were within the range reported for the general population. At least one prothrombotic condition was present in 38% of children and combined abnormalities in 8%. The incidence of DVT was 28% (25/90), and most DVTs were asymptomatic. None of the prothrombotic conditions showed a significant association with DVT. The population attributable risk (i.e. the risk of DVT in the overall population attributable to a specific condition) did not exceed 2.2%. CONCLUSION: Prothrombotic conditions did not have an important impact on the risk of DVT in children with short-term CVLs. The results of the study suggest that screening for prothrombotic conditions is not justified in this setting. PMID- 25131189 TI - Evaluation of 18S rDNA PCR assay using skin fragments as a diagnostic test for Trypanosoma caninum. AB - Trypanosoma caninum is a new species that has been recently identified in Brazil and infects domestic dogs. To date, no accurate diagnostic assays for this parasite have been established; thus, our aim was to evaluate more than one type of PCR for the diagnosis and molecular screening of T. caninum in 229 dogs living in Rio de Janeiro state. The tests were based on the amplification and sequencing of the 18S ribosomal DNA (rDNA) gene using healthy skin fragments. Additionally, PCR amplification of the kDNA minicircles region specific to the Leishmania genus was performed. The PCR results were compared with those of culture-based analysis performed with the same specimen. Using cultures, T. caninum and Leishmania chagasi were isolated from 11 and 12 dogs, respectively, whereas the 18S rDNA PCR assay detected parasitic infection in 35 dogs. Among these, 25 dogs showed an amplification pattern similar to T. caninum and 10 showed a pattern similar to L. chagasi; these results were confirmed by sequencing analysis. The kDNA PCR analysis showed that 14 dogs were positive for Leishmania infection. Of these, 2 dogs showed negative culture results and 12 were positive for L. chagasi, including 4 with negative 18S rDNA PCR results. Thus far, culture-based testing has been the only tool used successfully for T. caninum diagnosis. Our results demonstrate that 18S rDNA PCR-based test should be a useful diagnostic tool, particularly for distinguishing between T. caninum and L. chagasi infections in areas where these 2 parasites co-exist. PMID- 25131190 TI - On the use of posterior predictive probabilities and prediction uncertainty to tailor informative sampling for parasitological surveillance in livestock. AB - Model-based geostatistics and Bayesian approaches are appropriate in the context of Veterinary Epidemiology when point data have been collected by valid study designs. The aim is to predict a continuous infection risk surface. Little work has been done on the use of predictive infection probabilities at farm unit level. In this paper we show how to use predictive infection probability and related uncertainty from a Bayesian kriging model to draw a informative samples from the 8794 geo-referenced sheep farms of the Campania region (southern Italy). Parasitological data come from a first cross-sectional survey carried out to study the spatial distribution of selected helminths in sheep farms. A grid sampling was performed to select the farms for coprological examinations. Faecal samples were collected for 121 sheep farms and the presence of 21 different helminths were investigated using the FLOTAC technique. The 21 responses are very different in terms of geographical distribution and prevalence of infection. The observed prevalence range is from 0.83% to 96.69%. The distributions of the posterior predictive probabilities for all the 21 parasites are very heterogeneous. We show how the results of the Bayesian kriging model can be used to plan a second wave survey. Several alternatives can be chosen depending on the purposes of the second survey: weight by posterior predictive probabilities, their uncertainty or combining both information. The proposed Bayesian kriging model is simple, and the proposed samping strategy represents a useful tool to address targeted infection control treatments and surbveillance campaigns. It is easily extendable to other fields of research. PMID- 25131191 TI - Dysautonomic responses during percutaneous carotid intervention: principles of physiology and management. AB - Percutaneous carotid artery stenting (CAS) has emerged as a less invasive alternative to carotid endarterectomy for the treatment of carotid atherosclerotic disease. The main risk of CAS is the occurrence of neuro-vascular complications; however, carotid artery stenting-related dysautonomia (CAS-D) (hypertension, hypotension, and bradycardia) is the most frequently reported problem occurring in the periprocedural period. Alterations in autonomic homeostasis result from baroreceptor stimulation, which occurs particularly at the time of balloon inflation in the region of the carotid sinus. The response can be profound enough to induce asystole or even complete cessation of postganglionic sympathetic nerve activity. Frequency and factors predisposing a patient to CAS-D have been investigated in several studies; however, there are significant discrepancies in results among reports. Lack of consistent findings may arise from using different methods and definitions, as well as other factors discussed in detail in this review. Furthermore, a correlation of CAS-D with short and long-term outcomes has been investigated only in small and mostly retrospective studies, explaining why its prognostic significance remains uncertain. In this manuscript, we have focused on risk factors, pathophysiology and management of periprocedural autonomic dysfunction. As there is no standardized approach to the treatment of CAS-D, we present an algorithm for the periprocedural management of patients undergoing CAS. The proposed algorithm was developed based on our procedural experience as well as data from the available literature. The Yale Algorithm was successfully implemented at our institution and we are currently collecting data for short- and long-term safety. (c) 2014 Wiley Periodicals, Inc. PMID- 25131193 TI - Pre-conception and diabetes: are we doing enough? PMID- 25131192 TI - NEK9-dependent proliferation of cancer cells lacking functional p53. AB - Dysfunction of the p53 network is a major cause of cancer development, and selective elimination of p53-inactivated cancer cells therefore represents an ideal therapeutic strategy. In this study, we performed a microRNA target screen that identified NEK9 (NIMA-related kinase 9) as a crucial regulator of cell-cycle progression in p53-inactivated cancer cells. NEK9 depletion selectively inhibited proliferation in p53-deficient cancer cells both in vitro and in vivo. The resultant cell-cycle arrest occurred predominantly in G1 phase, and exhibited senescence-like features. Furthermore, NEK9 repression affected expression of a broad range of genes encoding cell-cycle regulators and factors involved in mRNA processing, suggesting a novel role for NEK9 in p53-deficient cells. Lung adenocarcinoma patients with positive staining for NEK9 and mutant p53 proteins exhibited significantly poorer prognoses, suggesting that expression of both proteins promotes tumor growth. Our findings demonstrate that a novel NEK9 network regulates the growth of cancer cells lacking functional p53. PMID- 25131194 TI - Diabetes and dementia in older people: a Best Clinical Practice Statement by a multidisciplinary National Expert Working Group. AB - Both dementia and diabetes mellitus are long-term disabling conditions and each may be a co-morbidity of the other. Type 2 diabetes is associated with a 1.5- to 2-fold higher risk of dementia. Diabetes also may occur for the first time in many individuals with mental ill health, including cognitive impairment and dementia, and this may complicate management and lead to difficulties in self care. Case finding is often poor for cognitive impairment in medical settings and for diabetes in mental health settings and this needs to be addressed in the development of care pathways for both conditions. Many other deficiencies in quality care (both for dementia and diabetes) currently exist, but we hope that this Best Clinical Practice Statement will provide a platform for further work in this area. We have outlined the key steps in an integrated care pathway for both elements of this clinical relationship, produced guidance on identifying each condition, dealt with the potentially hazardous issue of hypoglycaemia, and have outlined important competencies required of healthcare workers in both medical/diabetes and mental health settings to enhance clinical care. PMID- 25131195 TI - In-vivo imaging of the fracture healing in medaka revealed two types of osteoclasts before and after the callus formation by osteoblasts. AB - The fracture healing research, which has been performed in mammalian models not only for clinical application but also for bone metabolism, revealed that generally osteoblasts are induced to enter the fracture site before the induction of osteoclasts for bone remodeling. However, it remains unknown how and where osteoclasts and osteoblasts are induced, because it is difficult to observe osteoclasts and osteoblasts in a living animal. To answer these questions, we developed a new fracture healing model by using medaka. We fractured one side of lepidotrichia in a caudal fin ray without injuring the other soft tissues including blood vessels. Using the transgenic medaka in which osteoclasts and osteoblasts were visualized by GFP and DsRed, respectively, we found that two different types of functional osteoclasts were induced before and after osteoblast callus formation. The early-induced osteoclasts resorbed the bone fragments and the late-induced osteoclasts remodeled the callus. Both types of osteoclasts were induced near the surface on the blood vessels, while osteoblasts migrated from adjacent fin ray. Transmission electron microscopy revealed that no significant ruffled border and clear zone were observed in early-induced osteoclasts, whereas the late-induced osteoclasts had clear zones but did not have the typical ruffled border. In the remodeling of the callus, the expression of cox2 mRNA was up-regulated at the fracture site around vessels, and the inhibition of Cox2 impaired the induction of the late-induced osteoclasts, resulting in abnormal fracture healing. Finally, our developed medaka fracture healing model brings a new insight into the molecular mechanism for controlling cellular behaviors during the fracture healing. PMID- 25131196 TI - Drosophila protein kinase N (Pkn) is a negative regulator of actin-myosin activity during oogenesis. AB - Nurse cell dumping is an actin-myosin based process, where 15 nurse cells of a given egg chamber contract and transfer their cytoplasmic content through the ring canals into the growing oocyte. We isolated two mutant alleles of protein kinase N (pkn) and showed that Pkn negatively-regulates activation of the actin myosin cytoskeleton during the onset of dumping. Using live-cell imaging analysis we observed that nurse cell dumping rates sharply increase during the onset of fast dumping. Such rate increase was severely impaired in pkn mutant nurse cells due to excessive nurse cell actin-myosin activity and/or loss of tissue integrity. Our work demonstrates that the transition between slow and fast dumping is a discrete event, with at least a five to six-fold dumping rate increase. We show that Pkn negatively regulates nurse cell actin-myosin activity. This is likely to be important for directional cytoplasmic flow. We propose Pkn provides a negative feedback loop to help avoid excessive contractility after local activation of Rho GTPase. PMID- 25131197 TI - Gas2l3 is essential for brain morphogenesis and development. AB - Growth arrest-specific 2-like 3 (Gas2l3) is a newly discovered cell cycle protein and a cytoskeleton orchestrator that binds both actin filament and microtubule networks. Studies of cultured mammalian cells established Gas2l3 as a regulator of the cell division process, in particular cytokinesis and cell abscission. Thus far, the role of Gas2l3 in vivo remains entirely unknown. In order to investigate Gas2l3 in developing vertebrates, we cloned the zebrafish gene. Spatiotemporal analysis of gas2l3 expression revealed a ubiquitous maternal transcript as well as a zygotic transcript primarily restricted to brain tissues. We next conducted a series of loss-of-function experiments, and searched for developmental anomalies at the end of the segmentation period. Our analysis revealed abnormal brain morphogenesis and ventricle formation in gas2l3 knockdown embryos. This signature phenotype could be rescued by elevated levels of gas2l3 RNA. At the tissue level, gas2l3 downregulation interferes with cell proliferation, suggesting that the cell cycle activities of Gas2l3 are essential for brain tissue homeostasis. Altogether, this study provides the first insight into the function of gas2l3 in vivo, demonstrating its essential role in brain development. PMID- 25131198 TI - Conversion of the thymus into a bipotent lymphoid organ by replacement of FOXN1 with its paralog, FOXN4. AB - The thymus is a lymphoid organ unique to vertebrates, and it provides a unique microenvironment that facilitates the differentiation of immature hematopoietic precursors into mature T cells. We subjected the evolutionary trajectory of the thymic microenvironment to experimental analysis. A hypothetical primordial form of the thymus was established in mice by replacing FOXN1, the vertebrate-specific master regulator of thymic epithelial cell function, with its metazoan ancestor, FOXN4, thereby resetting the regulatory and coding changes that have occurred since the divergence of these two paralogs. FOXN4 exhibited substantial thymopoietic activity. Unexpectedly, histological changes and a functional imbalance between the lymphopoietic cytokine IL7 and the T cell specification factor DLL4 within the reconstructed thymus resulted in coincident but spatially segregated T and B cell development. Our results identify an evolutionary mechanism underlying the conversion of a general lymphopoietic organ to a site of exclusive T cell generation. PMID- 25131199 TI - The TSC complex is required for the benefits of dietary protein restriction on stress resistance in vivo. AB - Protein restriction (PR) is important for the benefits of dietary restriction on longevity and stress resistance, but relevant nutrient sensors and downstream effectors in mammals remain poorly defined. We used PR-mediated protection from hepatic ischemia reperfusion injury to probe genetic requirements for the evolutionarily conserved nutrient sensors GCN2 and mTORC1 in stress resistance. One week of PR reduced free amino acids and circulating growth factors, activating GCN2 and mTORC1 repressor tuberous sclerosis complex (TSC). However, although GCN2 was dispensable for PR-induced protection, hepatic TSC1 was required. PR improved hepatic insulin sensitivity in a TSC1-dependent manner prior to ischemia, facilitating increased prosurvival signaling and reduced apoptosis after reperfusion. These benefits were partially abrogated by pharmacological PI3K inhibition or genetic deletion of the insulin receptor in hepatocytes. In conclusion, improved insulin sensitivity upon short-term PR required TSC1, facilitated increased prosurvival signaling after injury, and contributed partially to PR-mediated resistance to clinically relevant ischemia reperfusion injury. PMID- 25131200 TI - A polymorphic enhancer near GREM1 influences bowel cancer risk through differential CDX2 and TCF7L2 binding. AB - A rare germline duplication upstream of the bone morphogenetic protein antagonist GREM1 causes a Mendelian-dominant predisposition to colorectal cancer (CRC). The underlying disease mechanism is strong, ectopic GREM1 overexpression in the intestinal epithelium. Here, we confirm that a common GREM1 polymorphism, rs16969681, is also associated with CRC susceptibility, conferring ~20% differential risk in the general population. We hypothesized the underlying cause to be moderate differences in GREM1 expression. We showed that rs16969681 lies in a region of active chromatin with allele- and tissue-specific enhancer activity. The CRC high-risk allele was associated with stronger gene expression, and higher Grem1 mRNA levels increased the intestinal tumor burden in Apc(Min) mice. The intestine-specific transcription factor CDX2 and Wnt effector TCF7L2 bound near rs16969681, with significantly higher affinity for the risk allele, and CDX2 overexpression in CDX2/GREM1-negative cells caused re-expression of GREM1. rs16969681 influences CRC risk through effects on Wnt-driven GREM1 expression in colorectal tumors. PMID- 25131202 TI - BRCA1 is a histone-H2A-specific ubiquitin ligase. AB - The RING domain proteins BRCA1 and BARD1 comprise a heterodimeric ubiquitin (E3) ligase that is required for the accumulation of ubiquitin conjugates at sites of DNA damage and for silencing at DNA satellite repeat regions. Despite its links to chromatin, the substrate and underlying function of the BRCA1/BARD1 ubiquitin ligase remain unclear. Here, we show that BRCA1/BARD1 specifically ubiquitylates histone H2A in its C-terminal tail on lysines 127 and 129 in vitro and in vivo. The specificity for K127-129 is acquired only when H2A is within a nucleosomal context. Moreover, site-specific targeting of the BRCA1/BARD1 RING domains to chromatin is sufficient for H2Aub foci formation in vivo. Our data establish BRCA1/BARD1 as a histone-H2A-specific E3 ligase, helping to explain its localization and activities on chromatin in cells. PMID- 25131201 TI - A macrohistone variant links dynamic chromatin compaction to BRCA1-dependent genome maintenance. AB - Appropriate DNA double-strand break (DSB) repair factor choice is essential for ensuring accurate repair outcome and genomic integrity. The factors that regulate this process remain poorly understood. Here, we identify two repressive chromatin components, the macrohistone variant macroH2A1 and the H3K9 methyltransferase and tumor suppressor PRDM2, which together direct the choice between the antagonistic DSB repair mediators BRCA1 and 53BP1. The macroH2A1/PRDM2 module mediates an unexpected shift from accessible to condensed chromatin that requires the ataxia telangiectasia mutated (ATM)-dependent accumulation of both proteins at DSBs in order to promote DSB-flanking H3K9 dimethylation. Remarkably, loss of macroH2A1 or PRDM2, as well as experimentally induced chromatin decondensation, impairs the retention of BRCA1, but not 53BP1, at DSBs. As a result, macroH2A1 and/or PRDM2 depletion causes epistatic defects in DSB end resection, homology-directed repair, and the resistance to poly(ADP-ribose) polymerase (PARP) inhibition-all hallmarks of BRCA1-deficient tumors. Together, these findings identify dynamic, DSB-associated chromatin reorganization as a critical modulator of BRCA1 dependent genome maintenance. PMID- 25131203 TI - Perturbation of NCOA6 leads to dilated cardiomyopathy. AB - Dilated cardiomyopathy (DCM) is a progressive heart disease characterized by left ventricular dilation and contractile dysfunction. Although many candidate genes have been identified with mouse models, few of them have been shown to be associated with DCM in humans. Germline depletion of Ncoa6, a nuclear hormone receptor coactivator, leads to embryonic lethality and heart defects. However, it is unclear whether Ncoa6 mutations cause heart diseases in adults. Here, we report that two independent mouse models of NCOA6 dysfunction develop severe DCM with impaired mitochondrial function and reduced activity of peroxisome proliferator-activated receptor delta (PPARdelta), an NCOA6 target critical for normal heart function. Sequencing of NCOA6-coding regions revealed three independent nonsynonymous mutations present in 5 of 50 (10%) patients with idiopathic DCM (iDCM). These data suggest that malfunction of NCOA6 can cause DCM in humans. PMID- 25131204 TI - Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury. AB - Hepatocytes provide most liver functions, but they can also proliferate and regenerate the liver after injury. However, under some liver injury conditions, particularly chronic liver injury where hepatocyte proliferation is impaired, liver stem cells (LSCs) are thought to replenish lost hepatocytes. Conflicting results have been reported about the identity of LSCs and their contribution to liver regeneration. To address this uncertainty, we followed candidate LSC populations by genetic fate tracing in adult mice with chronic liver injury due to a choline-deficient, ethionine-supplemented diet. In contrast to previous studies, we failed to detect hepatocytes derived from biliary epithelial cells or mesenchymal liver cells beyond a negligible frequency. In fact, we failed to detect hepatocytes that were not derived from pre-existing hepatocytes. In conclusion, our findings argue against LSCs, or other nonhepatocyte cell types, providing a backup system for hepatocyte regeneration in this common mouse model of chronic liver injury. PMID- 25131205 TI - Stabilization of cartwheel-less centrioles for duplication requires CEP295 mediated centriole-to-centrosome conversion. AB - Vertebrate centrioles lose their geometric scaffold, the cartwheel, during mitosis, concurrently with gaining the ability to recruit the pericentriolar material (PCM) and thereby function as the centrosome. Cartwheel removal has recently been implicated in centriole duplication, but whether "cartwheel-less" centrioles are intrinsically stable or must be maintained through other modifications remains unclear. Here, we identify a newborn centriole-enriched protein, KIAA1731/CEP295, specifically mediating centriole-to-centrosome conversion but dispensable for cartwheel removal. In the absence of CEP295, centrioles form in the S/G2 phase and lose their associated cartwheel in mitosis but cannot be converted to centrosomes, uncoupling the two events. Strikingly, centrioles devoid of both the PCM and the cartwheel progressively lose centriolar components, whereas centrioles associating with either the cartwheel or PCM alone can exist stably. Thus, cartwheel removal can have grave repercussions to centriole stability, and centriole-to-centrosome conversion mediated by CEP295 must occur in parallel to maintain cartwheel-less centrioles for duplication. PMID- 25131206 TI - Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus. AB - Thymic epithelial cells (TECs) are critical for T cell development and self tolerance but are gradually lost with age. The existence of thymic epithelial progenitors (TEPCs) in the postnatal thymus has been inferred, but their identity has remained enigmatic. Here, we assessed the entire adult TEC compartment in order to reveal progenitor capacity is retained exclusively within a subset of immature thymic epithelium displaying several hallmark features of stem/progenitor function. These adult TEPCs generate mature cortical and medullary lineages in a stepwise fashion, including Aire+ TEC, within fetal thymus reaggregate grafts. Although relatively quiescent in vivo, adult TEPCs demonstrate significant in vitro colony formation and self-renewal. Importantly, 3D-cultured TEPCs retain their capacity to differentiate into cortical and medullary TEC lineages when returned to an in vivo thymic microenvironment. No other postnatal TEC subset exhibits this combination of properties. The characterization of adult TEPC will enable progress in understanding TEC biology in aging and regeneration. PMID- 25131207 TI - Reconstruction of insulin signal flow from phosphoproteome and metabolome data. AB - Cellular homeostasis is regulated by signals through multiple molecular networks that include protein phosphorylation and metabolites. However, where and when the signal flows through a network and regulates homeostasis has not been explored. We have developed a reconstruction method for the signal flow based on time course phosphoproteome and metabolome data, using multiple databases, and have applied it to acute action of insulin, an important hormone for metabolic homeostasis. An insulin signal flows through a network, through signaling pathways that involve 13 protein kinases, 26 phosphorylated metabolic enzymes, and 35 allosteric effectors, resulting in quantitative changes in 44 metabolites. Analysis of the network reveals that insulin induces phosphorylation and activation of liver-type phosphofructokinase 1, thereby controlling a key reaction in glycolysis. We thus provide a versatile method of reconstruction of signal flow through the network using phosphoproteome and metabolome data. PMID- 25131208 TI - Nontranscriptional role of Hif-1alpha in activation of gamma-secretase and notch signaling in breast cancer. AB - gamma-Secretase is composed of four proteins that are obligatory for protease activity: presenilin, nicastrin, Aph1, and Pen-2. Despite the progress toward understanding the function of these individual subunits, there is no information available pertaining to the modulation of gamma-secretase in response to environmental changes in cells. Here, we show that hypoxia upregulates gamma secretase activity through a direct interaction with Hif-1alpha, revealing an unconventional function for Hif-1alpha as an enzyme subunit, which is distinct from its canonical role as a transcription factor. Moreover, hypoxia-induced cell invasion and metastasis are alleviated by either gamma-secretase inhibitors or a dominant-negative Notch coactivator, indicating that gamma-secretase/Notch signaling plays an essential role in controlling these cellular processes. The present study reveals a mechanism in which gamma-secretase can achieve temporal control through conditional interactions with regulatory proteins, such as Hif 1alpha, under select physiological and pathological conditions. PMID- 25131210 TI - Dysregulated expression of neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity. AB - Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an "optimal" level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect. PMID- 25131211 TI - Sequencing of captive target transcripts identifies the network of regulated genes and functions of primate-specific miR-522. AB - Identifying microRNA (miRNA)-regulated genes is key to understanding miRNA function. However, many miRNA recognition elements (MREs) do not follow canonical "seed" base-pairing rules, making identification of bona fide targets challenging. Here, we apply an unbiased sequencing-based systems approach to characterize miR-522, a member of the oncogenic primate-specific chromosome 19 miRNA cluster, highly expressed in poorly differentiated cancers. To identify miRNA targets, we sequenced full-length transcripts captured by a biotinylated miRNA mimic. Within these targets, mostly noncanonical MREs were identified by sequencing RNase-resistant fragments. miR-522 overexpression reduced mRNA, protein levels, and luciferase activity of >70% of a random list of candidate target genes and MREs. Bioinformatic analysis suggested that miR-522 regulates cell proliferation, detachment, migration, and epithelial-mesenchymal transition. miR-522 induces G1 cell-cycle arrest and causes cells to detach without anoikis, become invasive, and express mesenchymal genes. Thus, our method provides a simple but effective technique for identifying miRNA-regulated genes and biological function. PMID- 25131212 TI - Childhood florid follicular hyperplasia with immunoglobulin light-chain restriction in the gastrointestinal tract. AB - AIMS: Immunoglobulin light-chain expression is used routinely as an indirect marker of clonality for recognizing B cell lymphoproliferative disorders. METHODS AND RESULTS: Here we describe four floral follicular hyperplasia cases in the gastrointestinal tract (appendix and rectum) of children (4 to 6 years). Immunohistochemical studies revealed lambda light-chain restriction that was associated with polyclonal IgH pattern. Clinical features and follow-up of the patients did not reveal any other systemic symptoms, laboratory abnormalities or organ alterations. CONCLUSIONS: Recognition of this phenomenon is useful in the diagnosis of nodular lymphoid hyperplasia of the gastrointestinal tract, for avoiding overdiagnosis of lymphoid malignancies, and raises concerns that the identification of light-chain restriction is not necessarily a marker of monoclonality. PMID- 25131209 TI - Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease. AB - Macrophages can fuse to form osteoclasts in bone or multinucleate giant cells (MGCs) as part of the immune response. We use a systems genetics approach in rat macrophages to unravel their genetic determinants of multinucleation and investigate their role in both bone homeostasis and inflammatory disease. We identify a trans-regulated gene network associated with macrophage multinucleation and Kcnn4 as being the most significantly trans-regulated gene in the network and induced at the onset of fusion. Kcnn4 is required for osteoclast and MGC formation in rodents and humans. Genetic deletion of Kcnn4 reduces macrophage multinucleation through modulation of Ca(2+) signaling, increases bone mass, and improves clinical outcome in arthritis. Pharmacological blockade of Kcnn4 reduces experimental glomerulonephritis. Our data implicate Kcnn4 in macrophage multinucleation, identifying it as a potential therapeutic target for inhibition of bone resorption and chronic inflammation. PMID- 25131213 TI - Reconsidering the age thresholds for type II diabetes screening in the U.S. AB - BACKGROUND: Type II diabetes and its complications can sometimes be prevented, if identified and treated early. One fifth of diabetics in the U.S. remain undiagnosed. Commonly used screening guidelines are inconsistent. PURPOSE: To examine the optimal age cut-point for opportunistic universal screening, compared to targeted screening, which is recommended by U.S. Preventive Services Task Force (USPSTF) and American Diabetes Association (ADA) guidelines. METHODS: Cross sectional analysis of a nationally representative sample from the National Health and Nutrition Examination Survey, 2007-2010. Number of people needed to screen (NNS) to obtain one positive test result was calculated for different guidelines. Sampling weights were applied to construct national estimates. The 2010 Medicare fee schedule was used for cost estimation. Analysis was conducted in January 2014. RESULTS: NNS, under universal screening, drops sharply at age 35 years, from 80 (30-34-year-olds) to 31 (35-39-year-olds). Opportunistic universal screening of eligible people aged >=35 years would yield an NNS of 15, translating to $66 per positive test. Among people aged 35-44 years (who are not recommended for universal screening by ADA), most (71%) were overweight or obese and all had at least one other ADA risk factor. Only 34% of individuals aged >=35 years met USPSTF criteria. Strictly enforcing USPSTF guidelines would have resulted in a majority (61%) of potential positive test cases being missed (5,508,164 cases nationwide). CONCLUSIONS: Opportunistic universal screening among individuals aged >=35 years could greatly reduce the national prevalence of undiagnosed pre-diabetes or diabetes at relatively low cost. PMID- 25131215 TI - End-of-life care in pediatric neuro-oncology. AB - BACKGROUND: The management of children with cancer during the end-of-life (EOL) period is often difficult and requires skilled medical professionals. Patients with tumors of the central nervous system (CNS) with relapse or disease progression might have additional needs because of the presence of unique issues, such as neurological impairment and altered consciousness. Very few reports specifically concerning the EOL period in pediatric neuro-oncology are available. PROCEDURE: Among all patients followed at our center during the EOL, we retrospectively analyzed data from 39 children and adolescents with brain tumors, in order to point out on their peculiar needs. RESULTS: Patients were followed-up for a median time of 20.1 months. Eighty-two percent were receiving only palliative therapy before death. Almost half the patients (44%) died at home, while 56% died in a hospital. Palliative sedation with midazolam was performed in 58% of cases; morphine was administered in 51.6% of cases. No patient had uncontrolled pain. CONCLUSIONS: The EOL in children with advanced CNS cancer is a period of active medical care. Patients may develop complex neurological symptoms and often require long hospitalization. We organized a network-based collaboration among the reference pediatric oncology center, other pediatric hospitals and domiciliary care personnel, with the aim to ameliorate the quality of care during the EOL period. In our cohort, palliative sedation was widely used while no patients died with uncontrolled pain. A precise process of data collection and a better sharing of knowledge are necessary in order to improve the management of such patients. PMID- 25131216 TI - Controlled release of beta-carotene in beta-lactoglobulin-dextran-conjugated nanoparticles' in vitro digestion and transport with Caco-2 monolayers. AB - Undesirable aggregation of nanoparticles stabilized by proteins may occur at the protein's isoelectric point when the particle has zero net charge. Stability against aggregation of nanoparticles may be improved by reacting free amino groups with reducing sugars by the Maillard reaction. beta-Lactoglobulin (BLG) dextran conjugates were characterized by SDS-PAGE and CD. Nanoparticles (60-70 nm diameter) of beta-carotene (BC) encapsulated by BLG or BLG-dextran were prepared by the homogenization-evaporation method. Both BLG and BLG-dextran nanoparticles appeared to be spherically shaped and uniformly dispersed by TEM. The stability and release of BC from the nanoparticles under simulated gastrointestinal conditions were evaluated. Dextran conjugation prevented the flocculation or aggregation of BLG-dextran particles at pH ~4-5 compared to very large sized aggregates of BLG nanoparticles. The released contents of BC from BLG and BLG dextran nanoparticles under acidic gastric conditions were 6.2 +/- 0.9 and 5.4 +/ 0.3%, respectively. The release of BC from BLG-dextran nanoparticles by trypsin digestion was 51.8 +/- 4.3% of total encapsulated BC, and that from BLG nanoparticles was 60.9 +/- 2.9%. Neither BLG-BC nanoparticles nor the Maillard reacted BLG-dextran conjugates were cytotoxic to Caco-2 cells, even at 10 mg/mL. The apparent permeability coefficient (Papp) of Caco-2 cells to BC was improved by nanoencapsulation, compared to free BC suspension. The results indicate that BC-encapsulated beta-lactoglobulin-dextran-conjugated nanoparticles are more stable to aggregation under gastric pH conditions with good release and permeability properties. PMID- 25131214 TI - Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder. AB - Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype. PMID- 25131218 TI - Low-magnitude high-frequency vibration enhances gene expression related to callus formation, mineralization and remodeling during osteoporotic fracture healing in rats. AB - Low magnitude high frequency vibration (LMHFV) has been shown to improve anabolic and osteogenic responses in osteoporotic intact bones and during osteoporotic fracture healing; however, the molecular response of LMHFV during osteoporotic fracture healing has not been investigated. It was hypothesized that LMHFV could enhance osteoporotic fracture healing by regulating the expression of genes related to chondrogenesis (Col-2), osteogenesis (Col-1) and remodeling (receptor activator for nuclear factor- kappa B ligand (RANKL) and osteoproteger (OPG)). In this study, the effects of LMHFV on both osteoporotic and normal bone fracture healing were assessed by endpoint gene expressions, weekly radiographs, and histomorphometry at weeks 2, 4 and 8 post-treatment. LMHFV enhanced osteoporotic fracture healing by up-regulating the expression of chondrogenesis-, osteogenesis and remodeling-related genes (Col-2 at week 4 (p=0.008), Col-1 at week 2 and 8 (p<0.001 and p=0.008) and RANKL/OPG at week 8 (p=0.045)). Osteoporotic bone had a higher response to LMHFV than normal bone and showed significantly better results as reflected by increased expression of Col-2 and Col-1 at week 2 (p<0.001 for all), larger callus width at week 2 (p=0.001), callus area at week 1 and 5(p<0.05 for all) and greater relative area of osseous tissue (p=0.002) at week 8. This study helps to understand how LMHFV regulates gene expression of callus formation, mineralization and remodeling during osteoporotic fracture healing. PMID- 25131217 TI - Late diagnosis of hepatitis C virus infection in the Chronic Hepatitis Cohort Study (CHeCS): Missed opportunities for intervention. AB - To determine the stage of liver disease at initial diagnosis of hepatitis C virus (HCV) infection, we analyzed data from the Chronic Hepatitis Cohort Study (CHeCS), a large U.S. observational study. We examined the temporal relationships of initial HCV infection diagnosis with cirrhosis-defined by liver biopsy or mean FIB-4 score >5.88-and time to onset of cirrhotic decompensation in electronic medical records. We determined time in the health system prior to HCV diagnosis and rates of hospitalization and death following HCV diagnosis. Of 14,717 patients with chronic HCV seen during 2006-2011, 6,166 (42%) had a definable time of initial HCV diagnosis. Of these, 1,056 (17%) patients met our definition for "late diagnosis" with either cirrhosis concurrent with initial HCV diagnosis (n = 550), a first diagnosis of hepatic decompensation before or within 12 months after initial HCV diagnosis (n = 506), or both (n = 314). Patients with late diagnosis had an average of 6 years in the health system before their HCV diagnosis. In a comparison with patients without late diagnosis, hospitalization (59% versus 35%) and death (33% versus 9%) were more frequent among patients with late diagnosis. Among all who died, mean (median) time from initial HCV diagnosis to death was 4.8 (4.2) years. CONCLUSION: Many CHeCS patients had advanced liver disease concurrent with their initial HCV diagnosis despite many years of engagement with the healthcare system, and these patients had high rates of hospitalization and mortality. PMID- 25131219 TI - Comparison of 2-limb versus 3-limb electrodiagnostic studies in the evaluation of chronic inflammatory demyelinating polyneuropathy. AB - INTRODUCTION: European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic (EDx) criteria for the definite diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) require the presence of demyelinating findings (DF) in at least 2 nerves. Data are lacking, however, regarding the optimal number of nerves to test. METHODS: We retrospectively reviewed EDx data from 53 patients with CIDP and compared the number of DF found on 2- and 3-limb testing. RESULTS: A median of 3 (range 2-5) DF were found on 2 limb testing compared with 5 (range 4-7) DF when 3 limbs were evaluated. Two-limb EDx studies were sufficient to diagnose definite CIDP in 92.3% of typical, 84.2% of asymmetric, and 66.7% of distal phenotypes. Testing a third limb increased diagnostic certainty in 11 patients (20.8%) to definite CIDP. CONCLUSIONS: Three limb testing may increase diagnostic sensitivity of definite CIDP, especially in patients with atypical phenotypes. Larger prospective studies are needed to better assess the benefit of performing 3-limb EDx studies. PMID- 25131220 TI - Multi-omics analysis of inflammatory bowel disease. AB - Crohn's disease and ulcerative colitis, known together as inflammatory bowel disease (IBD), are severe autoimmune disorders now causing gut inflammation and ulceration, among other symptoms, in up to 1 in 250 people worldwide. Incidence and prevalence of IBD have been increasing dramatically over the past several decades, although the causes for this increase are still unknown. IBD has both a complex genotype and a complex phenotype, and although it has received substantial attention from the medical research community over recent years, much of the etiology remains unexplained. Genome-wide association studies have identified a rich genetic signature of disease risk in patients with IBD, consisting of at least 163 genetic loci. Many of these loci contain genes directly involved in microbial handling, indicating that the genetic architecture of the disease has been driven by host-microbe interactions. In addition, systematic shifts in gut microbiome structure (enterotype) and function have been observed in patients with IBD. Furthermore, both the host genotype and enterotype are associated with aspects of the disease phenotype, including location of the disease. This provides strong evidence of interactions between host genotype and enterotype; however, there is a lack of published multi-omics data from IBD patients, and a lack of bioinformatics tools for modeling such systems. In this article we discuss, from a computational biologist's point of view, the potential benefits of and the challenges involved in designing and analyzing such multi omics studies of IBD. PMID- 25131221 TI - Current status of anticoagulant treatments and improvements for hemodialysis patients in northern Chinese cities: a five-year comparative study. AB - BACKGROUND: Anticoagulation treatments are an important aspect of hemodialysis; however, few reports have addressed these treatments. This investigation intends to increase the understanding of the current status and improvements of hemodialysis-related anticoagulation treatments in China. METHODS: In this study, an epidemiological investigation was conducted that examined 842 patients in 2007 and 1 175 patients in 2012 who underwent hemodialysis anticoagulation treatments in seven blood purification centers in northern Chinese cities. RESULTS: Heparin was the most commonly used anticoagulant, although the percentage of use of low molecular-weight heparin (LMWH) increased from 26.5% in 2007 to 42.1% in 2012. In 2007, there were no significant differences in anticoagulant selection among either patients with various primary diseases or patients with hemorrhage, thrombosis, thrombocytopenia, or a low hemoglobin level. However, compared with patients with other diseases, significantly lower doses of LMWH were administered to patients with hypertension (55.5 U/kg vs. 67.3 U/kg, P < 0.05) or diabetes (58.5 U/kg vs. 67.3 U/kg, P < 0.05), and patients with hemorrhage received lower doses of heparin than the other patients (61.6 U/kg vs. 71.8 U/kg, P < 0.01). In 2012, patients with diabetic nephropathy (51.5% vs. 36.5%, P < 0.01), hemorrhage (43.4% vs. 31.7%, P < 0.01), or a hemoglobin level below 90 g/L (57.2% vs. 37.1%, P < 0.01) experienced significantly higher doses of LMWH administration; patients with hemorrhage received significantly reduced LMWH dosages (50.4 U/kg vs. 57.8 U/kg, P < 0.05), and patients with thrombosis received significantly higher doses of heparin (73.8 U/kg vs. 62.1 U/kg, P < 0.01) or LMWH (57.8 U/kg vs. 52.6 U/kg, P < 0.05). Antiplatelet drugs were administered to 20.4% of the examined patients in 2007 and 20.7% in 2012. In 2012, patients with hypertension (25.9% vs. 18.5%, P < 0.01) and thrombosis (36.6% vs. 16.1%, P < 0.01) had a higher rate of using antiplatelet drugs than patients with other primary diseases and complications. Patients receiving antiplatelet drugs also received higher doses of heparin than patients without using antiplatelet drugs (74.4 U/kg vs. 65.9 U/kg, P < 0.01). However, the use of the drugs was not correlated with thrombocytopenia. The rate at which coagulation indices were determined increased from 45.7% in 2007 to 64% in 2012. CONCLUSION: These findings suggested that hemodialysisrelated anticoagulation treatments in China have gradually become more standardized and individualized. PMID- 25131222 TI - Diagnostic utility of N-terminal-proBNP in differentiating acute pulmonary embolism from heart failure in patients with acute dyspnea. AB - BACKGROUND: The plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level is frequently elevated in dyspnoeic patients and increasingly used in emergency departments to assess the cause of acute dyspnea. In this study we prospectively tested NT-proBNP levels in patients with congestive heart failure (CHF) and/or acute pulmonary embolism (APE) and determined the utility of NT proBNP for discriminating APE from CHF. METHODS: A cohort of 177 dyspnoeic patients with a diagnosis of APE and/or CHF was prospectively studied between June 2010 and March 2013. NT-proBNP was measured by the electrochemiluminescence immunoassay (ECLIA). All patients were evaluated with transthoracic echocardiography (TTE). APE was diagnosed in the presence of thrombi signs in the pulmonary arteries with computed tomographic pulmonary angiography (CTPA) or a high-probability lung ventilation/perfusion scan. Risk stratification was based on the evaluation on admission according to the ESC guidelines from 2008. The diagnosis of CHF was based on the guidelines of the American College of Cardiology/American Heart Association and the European Society of Cardiology. Two physicians independently reviewed the records to determine the final diagnosis. RESULTS: Fifty-nine patients met the criteria for dyspnea caused by APE, and 113 patients were diagnosed with CHF. Most of the APE patients (41, 69.5%) were intermediate-risk. The symptoms and signs, such as orthopnea, paroxysmal nocturnal dyspnea and rales in the lungs, were more common in patients with CHF than in patients with APE (P < 0.01). Median NT-proBNP was significantly lower in patients with APE compared to those in patients with CHF (2 855.9 pg/ml vs. 6 911.4 pg/ml, P < 0.01). We constructed the receiver operating characteristics (ROC) curve in predicting the diagnosis of APE. At a cut point = 1 582.750 pg/ml, NT-proBNP provided a specificity of 93% and a true positive rate (sensitivity) of 17% for the diagnosis. At a cut point = 3 390.000 pg/ml, NT-proBNP had a specificity of 83% and a sensitivity of 84% for the diagnosis of APE. At a cut point = 6 486.500 pg/ml, they were 54% and 93% respectively. CONCLUSIONS: NT proBNP can assist in excluding CHF patients from those admitted to the emergency department with acute dyspnea and identifying patients with a high probability of APE, which would reduce the missed diagnosis of APE. Larger studies are necessary to validate these findings. PMID- 25131223 TI - Tartrate-resistant acid phosphatase 5b is a potential biomarker for rheumatoid arthritis: a pilot study in Han Chinese. AB - BACKGROUND: Bone damage around the joints is one of the major pathophysiological mechanisms that leads to rheumatoid arthritis (RA) chronic disability. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) is secreted by osteoclasts, its activity can be used as a clinically relevant bone resorption marker. The aim of this study was to test whether the measurement of serum levels of TRACP-5b in patients with RA would correlate with measures of disease activity and with responses to therapy. METHODS: Fifty-six patients were randomly assigned to receive recombinant human cytotoxic tlymphocyte-associated antigen-4 immunoglobulin (RhCTLA4-Ig), infliximab or methotrexate (MTX). The clinical and serologic indicators of RA activity were evaluated at baseline and at 24 weeks. Serum TRACP-5b was measured by Enzyme-linked Immunosorbent Assay (ELISA) at 0, 12 and 24 weeks. Hand X-rays were obtained at baseline. RESULTS: At baseline, the levels of TRACP-5b correlated with the severity of X-ray damage, disease duration (r = 0.332, P = 0.012), and tender joint count (r = 0.408, P = 0.002). The 24 weeks values of TRACP-5b for RhCTLA4-Ig group and infliximab group differed significantly from the baseline values in each group (P < 0.05; P < 0.05), whereas only the value for RhCTLA4-Ig group differed significantly from the 24 weeks value for the MTX group (P < 0.01). Considering the two biologics-treated groups together, the TRACP-5b levels at 24 weeks differed significantly from the baseline values only in those patients who reached an ACR70 level (P < 0.05). CONCLUSIONS: Measurement of serum TRACP-5b in RA patients reflects clinical and radiological measures of disease activity, treatment with certain biologics, and degree of response to therapy. TRACP-5b should be investigated further as a potential biomarker to predict response to therapy, including slowing of radiographic progression. PMID- 25131224 TI - Augmentation plating in hypertrophic non-union after nail fixation of femoral shaft fracture compared with exchange plating. AB - BACKGROUND: Augmentation plating has been used successfully to treat hypertrophic non-union after nail fixation. This study compared the efficacy of augmentation plating and exchange plating for treating hypertrophic non-union of femoral shaft fracture after intramedullary nail fixation. METHODS: A total of 12 patients received augmentation plating and 15 patients received exchange plating as treatment for femoral shaft hypertrophic non-union. The procedures were conducted at our medical centre between January 2005 and January 2012. Clinical follow-up was conducted at 2 weeks, 1 month and then monthly until union was achieved to compare union time, operation time, bleeding and complications between the two groups. RESULTS: All patients underwent follow-up examinations until fracture union was achieved. The average length of follow-up time after the second treatment was (18.37 +/- 3.28) months. The time needed for union was (4.17 +/- 0.94) months in the augmentation plating group and (5.33 +/- 1.72) months in the exchange plating group. The operation time was (90.00 +/- 17.58) minutes in the augmentation plating group and (160.00 +/- 25.35) minutes in the exchange plating group. The amount of blood loss during the operation was (270.00 +/- 43.32) ml in the augmentation plating group and (530.00 +/- 103.65) ml in the exchange plating group. Both groups showed significant difference (P < 0.05) in their results. No complications were reported after the second operation. CONCLUSIONS: Augmentation plating after nail fixation could remove local rotation instability, facilitate simple operation, create minimal damage and enable exercise for early functional recovery. Therefore, augmentation plating is excellent for treating hypertrophic non-union after nail fixation in femoral shaft fracture. PMID- 25131225 TI - Intravitreal ranibizumab for the treatment of pathological myopia associated with choroidal neovascularization in Chinese patients. AB - BACKGROUND: Pathological myopia (PM) is the leading cause for choroidal neovascularization (CNV) in people below 50 years of age, the anti-vascular endothlial growth factor (VEGF) medicine is now available to treat CNV secondary to PM. This study aimed to observe the efficacy of intravitreal ranibizumab for PM associated with subfoveal or juxtafoveal CNV in Chinese patients. METHODS: Fifty-four eyes of 52 consecutive patients were included, they treated with intravitreal ranibizumab 0.5 mg for PM associated with CNV. The best corrected visual acuity (BCVA) of Snellen chart, letters of ETDRS chart, retinal thickness, leakage of CNV lesion, and complications with surgery were analyzed pre- and post treatment. Eligibility criteria included diopter >=-8.0 D or eye axis >= 28 mm with fundus changes of PM (lacquer crack, optic disc atrophy, chorioretinal atrophy, posterior scleral staphyloma); CNV secondary to PM; subfoveal or juxtafoveal CNV. RESULTS: For 54 affected eyes of 52 consecutive patients, the average BCVA of Snellen chart and letters of ETDRS chart were 0.29 and 30.4, respectively; fundus fluorescein angiography (FFA)/indocyanine green angiography (ICGA) showed CNV leakage, and average retinal thickness on optical coherence tomography (OCT) was 267.2 um before treatment. Injections of ranibizumab ranged from 1 to 4 (mean 2.2). Follow-up time varied from 12 to 36 months (mean 31.9 months). At the last visit, the BCVA of Snellen chart was increased by three lines (mean 0.65) (P < 0.01); the letters of ETDRS chart were increased to 17.0 letters (mean 47.4, P < 0.01); the visual acuity increased more than 15 letters in 30 eyes (55.5%), decreased in 1 eye (1.9%); the retinal thickness on OCT images was decreased by 17.0 um (mean 250.2 um) (P = 0.082); no active leakage from the CNV lesion occurred in 18 eyes (33.3%), reduced leakage in 30 eyes (55.6%), and no change in 6 eyes (11.1%) as shown by FFA/ICGA. Increased retinoschisis was observed in one eye after the second injection. CONCLUSIONS: Intravitreal ranibizumab for neovascular PM was well tolerated in Chinese patients, with functional and anatomic improvements in a short-term study, while a long-term study is still needed. PMID- 25131226 TI - Strabismus surgery distribution during 10-year period in a tertiary hospital. AB - BACKGROUND: There is no large population-based study of the distribution and changing trend of strabismus surgeries in China. This study aimed to investigate the distribution and the changing trend of strabismus surgery in a tertiary hospital of China. METHODS: A retrospective study of all the strabismus surgeries performed in Beijing Tongren Eye Center from 2003 to 2012 was carried out. Characteristics analyzed included the type of strabismus, age, and gender. RESULTS: Totally 26 524 strabismus surgeries were performed in Tongren Eye Center during the 10-year period. The number of surgeries increased steadily from 1 507 in 2003 to 3 482 in 2008 and slightly decreased to 3 124 in 2009, but there was a sharp drop to 2 569 in 2010 and then kept relatively steady at 2 760 in 2011 and 2 463 in 2012. Intermittent exotropia (30.3%) was the most common among all kinds of strabismus. The number of strabismus surgeries performed on children under 12 years of age (43.60%) was significantly higher than those of the other age groups (P < 0.05). Unilateral superior oblique paralysis was the most common subtype of paralytic strabismus (8.64%). CONCLUSIONS: The type distribution of strabismus surgery has changed during the recent decade. The age and type distribution of different strabismus remained basically constant, among which intermittent exotropia was the most common. PMID- 25131227 TI - Relationship between chronic diarrhea with normal colonoscopy findings and terminal ileum lesions. AB - BACKGROUND: The causes and mechanisms of chronic diarrhea are complex. This study aimed to explore the relationship between chronic diarrhea with normal colonoscopy findings and terminal ileum lesions. METHODS: All cases were collected from January 2009 to June 2010. The 40 patients in the patient group had chronic diarrhea with normal colonoscopy findings. Those who had hyperthyroidism, diabetes, chronic pancreatitis, cirrhosis, atrophic gastritis, short bowel syndrome and connective tissue diseases had been excluded. The control group contained 40 healthy individuals without diarrhea. Endoscopy of the terminal ileum was applied in both groups, with the endoscope inserted into terminal ileum for more than 20 cm. The patients diagnosed of chronic diarrhea with terminal ileum lesions were treated with metronidazole and probiotics for 10 14 days. RESULTS: Before treatment there were significant differences in endoscopy findings of the terminal ileum between the two groups (P < 0.05). In the patient group, endoscopy showed congestion, edema, erosion and ulcers in 29 cases, hyperplasia and enlargement of lymphoid follicles in 10 cases with a maximal diameter of 7-8 mm, and 1 case showed normal endoscopy results. After treatment, 35 patients recovered from diarrhea, and terminal ileum lesions disappeared in 30 cases as determined by endoscopy. In the control group, endoscopy showed scattered hyperplasia of lymphoid follicles in 5 cases, and the follicles were small with the maximal diameter being 3 mm. There was no hyperemia, edema, erosion or ulcers. CONCLUSIONS: Chronic diarrhea patients with normal colonoscopy findings may have lesions in the terminal ileum that can be detected by endoscopy; including hyperemia, erosion, ulcers and lymphoid follicle hyperplasia. Therapeutic effect is good with metronidazole and probiotics. PMID- 25131228 TI - Prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer. AB - BACKGROUND: The prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer (NSCLC) remains unclear. This study intends to identify the prognostic factors and to optimize treatments for these patients under update conditions. METHODS: The data of 124 NSCLC patients who underwent R1 resection at the bronchial stump was reviewed. There were 41 patients in the surgery group (S), 21 in the postoperative radiotherapy (PORT) group (S+R), 30 in the postoperative chemotherapy (POCT) group (S+C), and 32 in the PORT plus POCT group (S+R+C). The constitute proportion in different groups was tested using the chi(2) method, univariate analysis was performed using the Kaplan-Meier and log rank method, and multivariate analysis was done using the Cox hazard regression with entry factors including age, sex, pathological type and stage, classification of the residual disease, and treatment procedure. The process was performed stepwise backward with a maximum iteration of 20 and an entry possibility of 0.05 as well as an excluded possibility of 0.10 at each step. RESULTS: In univariate analysis, survival was more favorable for patients with squamous cell carcinoma, early pathological T or N stage, and chemotherapy or radiotherapy. There was no significant difference in the survival for patients with different types of the residual disease, except for the difference between patients with carcinoma in situ and lymphangiosis carcinomatosa (P = 0.030). The survival for patients receiving chemoradiotherapy was superior to that for those undergoing surgery alone (P = 0.016). In multivariate analysis, the pathological type (HR 2.51, 95% CI 1.59 to 3.96, P = 0.000), pathological T (HR 1.29, 95% CI 1.04 to 1.60, P = 0.021) or N stage (HR 2.04, 95% CI 1.40 to 2.98, P = 0.000), and chemotherapy (HR 0.24, 95% CI 0.13 to 0.43, P = 0.000) were independent prognostic factors. CONCLUSION: Patients with squamous cell carcinoma, early pathological T or N stage, or receiving chemotherapy had a more favorable prognosis. PMID- 25131229 TI - Analysis of risk factors affecting the prognosis of pancreatic neuroendocrine tumors. AB - BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) are a type of tumors with the characteristics of easy metastasis and recurrence. Till date, the risk factors affecting the prognosis are still in the debate. In this study, several risk factors will be discussed combined with our cases and experience. METHODS: Thirty-three patients diagnosed as pNETs were enrolled and the clinical features, blood tests, pathological features, surgical treatment, and follow-up data of these patients were collected and analyzed. RESULTS: In this study, operation time of G3 cases was longer than G1/G2 cases (P = 0.017). The elevated level of tumor markers such as AFP, CEA, Ca125, and Ca19-9 may predict easier metastasis, earlier recurrence, and poor prognosis (P = 0.007). The presence of cancer embolus and nerve invasion increases along with the TNM stage (P = 0.037 and P = 0.040), and the incidence of positive surgical margin increased (P = 0.007). When the presence of nerve invasion occurs, the chance of cancer embolus and lymph node metastasis also increases (P = 0.016 and P = 0.026). CONCLUSIONS: pNETs were tumors with the features of easy recurrence and metastasis and many risk factors could affect its prognosis such as the elevated levels of tumor markers and the presence of nerve invasion, except some recognized risk factors. If one or more of these factors existed, postoperative treatments may be needed to improve prognosis. PMID- 25131230 TI - Effect of fixing distal radius fracture with volar locking palmar plates while preserving pronator quadratus. AB - BACKGROUND: L-shaped incision of pronator quadratus (PQ) muscle along its radial and distal borders was always taken for distal radius fractures reduction and internal fixation. Repair of the PQ muscle was always recommended at the end of operation for some instructive reasons. But repair of PQ is not satisfied because of poor quality of muscle and fascial tissues which may cause pain or impede forearm pronation and supination for post-operative scarring around PQ. Inserting the locking palmar plate to pass under the pronator quadratus muscle and the locking screws are inserted through mini-incisions in pronator quadratus in some patients with distal radius fractures is a reasonable technique which can preserve the pronator quadratus. The purpose of this study was to evaluate and compare the clinical effects after volar plating of the distal radius fractures while preserving the pronator quadratus and pronator quadratus repair. METHODS: Between September 2010 and April 2012, 65 patients (42 males and 23 females; aged 20-68 years and a mean age of 42.5 years) with distal radius fracture underwent open reduction and internal fixation using the volar locking palmar plates (Depuy or Smith companies). The patients were classified as 23A-2 through 23C-3 according to the Orthopaedic Trauma Association (OTA) classifications. All surgeries were completed by the same trained team. The volar locking palmar plates of distal radius performed with preserving pronator quadratus group involved 30 patients including 19 males and 11 females and performed with pronator quadratus repair group involved 35 patients including 23 males and 12 females. We compared the two groups for wrist pain, forearm range of motion, grip strength, perioperative complications and wrist functional recovery score. RESULTS: The minimum follow-up for the whole cohort was one year. The differences between the two groups were significant with regard to wrist pain, forearm range of motion, grip strength and wrist function at 1, 2, and 6 weeks postoperatively, but insignificant at 6 and 12 months postoperatively. No significant differences were found in the perioperative complications and radiographs postoperatively. CONCLUSIONS: Preservation of the pronator quadratus muscle is a satisfactory method for the treatment of majority of the fractures of the distal radius with volar locking palmar plates, as this technique can yield better early wrist function and shorten the rehabilitation. PMID- 25131231 TI - En bloc resection concept for endoscopic endonasal nasopharyngectomy: surgical anatomy and outcome. AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) patients have a 19%-56% locoregional recurrence rate after primary therapy. For those recurrent NPC (rNPC) patients, re-irradiation may cause some complications. In recent years, endoscopic endonasal nasopharyngectomy (EEN) has become a surgical option for rNPC patients. Here we introduce the concept of en bloc excision (EBE) technique for EEN, including the surgical technique and clinical outcomes. METHODS: A retrospective study was conducted covering September 2009 to May 2013, involving the collection of locoregional rNPC cases from two institutions (Kuang-Tien General Hospital (KTGH) in Taiwan and National University Health System (NUHS) in Singapore). These patients failed prior therapy and then underwent EEN. We reported the 2 year overall survival rate, the 2-year disease-free survival rate, and related complications. RESULTS: Nine patients (five from KTGH and four from NUHS) completed this study, with five, two, and two patients of recurrence tumors (rT1), rT2, and rT3, respectively. The mean age was 46.4 years (range 32-63); the mean follow-up period was 24.9 months (range 10-45). The 2-year survival rate and the 2-year disease-free rate were 100% and 80%, respectively, in five patients. No significant complications or cases of mortality occurred. CONCLUSIONS: The EBE concept of EEN is suitable for early rT1 and has relatively encouraging short term outcomes. In selected rT2, careful EBE can be performed by expanding the surgical field. A clear view of the internal carotid artery-related anatomy is indispensable. In the future, more series may be needed to determine the role of EEN in rNPC patients. PMID- 25131232 TI - Influence of tube voltage on digitized image qualityof patients exposed to occupational dust: phantoms and clinical studies. AB - BACKGROUND: High-voltage analog X-ray examination is a main tool for pneumoconiosis, which is challenged by digital radiography (DR). The tube voltage of DR chest films required for diagnosis and staging of pneumoconiosis is concerned technically. We investigated the influence of the tube voltage on chest X-ray DR image quality of patients exposed to occupational dust. METHODS: DR images of the CDRAD2.0model, an anatomical chest phantom, and 136 exposed workers were analyzed at different tube voltages by threereaders. Image quality factors (IQF) were calculated and compared using the CDRAD2.0 model. DR images of ten anatomic positions were scored against those of the high-kilovolt chest films in anatomical phantom and clinical cases, and differences in scores were analyzed. RESULTS: In the CDRAD2.0 model, all three readers had a minimal IQF at 120 kV (mean: 22.25 kV). The differences in the mean IQF of DR images at different tube voltages was significant (F = 13.78, P < 0.001). The IQF of DR imaging at 120 kV was similar to high kilovolt analog imaging (t = -0.58, P > 0.05). In the anatomic phantom and clinical cases, the DR images at 120 kV were closest in anatomical detail to the high kV analog images, and the means were similar (P > 0.05). CONCLUSIONS: Among different tube voltages, DR image quality is closest to the high kilovolt analog images at 120 kV in patients exposed to occupational dust. PMID- 25131233 TI - Dynamic long-term microstructural and ultrastructural alterations in sensory nerves of rats of paclitaxel-induced neuropathic pain. AB - BACKGROUND: Paclitaxel, as a first line anti-neoplastic compound, frequently produces long-term pain after tumors have been treated. Clinical manifestations are varied and non-specific. Pathology of the nervous system during the development of the neuropathic pain is unclear. Thus, early diagnosis and treatment is often unsatisfying for patients. This study aimed to promote considerate understanding of the structural alteration of sensory nerves. METHODS: All rats were simply randomized into 3 groups: paclitaxel group, vehicle group and saline group. An established rat model of paclitaxel-induced peripheral neuropathy (2 mg/kg) was chosen for our research, behavior tests were operated during the procedure of 56 days. All rats were sampled on days 0, 3, 7, 28 and 56. The hind paw plantar skin, sciatic nerves, dorsal root ganglion and attached fibers, and lumbar spinal cord were processed for light and electron microscopy. The differences among 3 groups were analyzed with one-way analysis of variance (ANOVA). RESULTS: We affirmed that paclitaxel-induced mechano-allodynia and mechano-hyperalgesia occured after a 3-7-day delay, and this pain peaked at day 28 and persisted to day 56. Paclitaxel and vehicle treatment both evoked thermal hyperalgesia. Paclitaxel-induced axonal and myelin sheath degeneration was evident. At days 3 and 7, significant increases in atypical mitochondria in both myelinated axons and C-fibers of paclitaxel-treated nerves indicated that injured mitochondria correlated to specific paclitaxel-induced neuropathic pain, and the abnormity sustained till day 56. Microtubule was unaffected in myelinated axons or C-fibers in paclitaxel- or vehicle-treated rats. Significant increase of G ratio was evident with paclitaxel injection at days 7 and 28. CONCLUSION: Our research suggests a causal role for axonal degeneration, abnormalities in axonal mitochondria, and structural modification of axonal microtubules in paclitaxel induced neuropathic pain, and the abnormal mitochondria could be connected to the chronic neuropathic pain. PMID- 25131234 TI - Short-term intensive atorvastatin therapy improves endothelial function partly via attenuating perivascular adipose tissue inflammation through 5-lipoxygenase pathway in hyperlipidemic rabbits. AB - BACKGROUND: Atherosclerosis is a kind of disease with multiple risk factors, of which hyperlipidemia is a major classical risk factor resulting in its pathogenesis and development. The aim of this study was to determine the effects of short-term intensive atorvastatin (IA) therapy on vascular endothelial function and explore the possible mechanisms that may help to explain the clinical benefits from short-term intensive statin therapy. METHODS: After exposure to high-fat diet (HFD) for 8 weeks, the animals were, respectively, treated with IA or low-dose atorvastatin (LA) for 5 days. Blood lipids, C reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO), endothelin-1 (ET-1), and endothelium-dependent vasorelaxation function were, respectively, measured. mRNA and protein expression of CRP, TNF-alpha, IL-6, macrophage chemoattractant protein-1 (MCP-1), and 5 lipoxygenase (5-LO) were also evaluated in pericarotid adipose tissue (PCAT) and cultured adipocytes. RESULTS: HFD increased serum inflammatory factor levels; induced significant hyperlipidemia and endothelial dysfunction, including imbalance between NO and ET-1; enhanced inflammatory factors and 5-LO expression; and promoted macrophage infiltration into adipose tissue. Five-day IA therapy could significantly decrease serum inflammatory factor levels and their expression in PCAT; restore the balance between NO and ET-1; and improve endothelial function and macrophage infiltration without significant changes in blood lipids. However, all of the above were not observed in LA therapy. In vitro experiment found that lipopolysaccharide (LPS) enhanced the expression of inflammatory factors and 5-LO in cultured adipocytes, which could be attenuated by short-time (6 hours) treatment of high-dose (5 umol/L) but not low-dose (0.5 umol/L) atorvastatin. In addition, inhibiting 5-LO by Cinnamyl-3,4-dihydroxy alpha-cyanocinnamate (CDC, a potent and direct 5-LO inhibitor) could significantly downregulate the above-mentioned gene expression in LPS-treated adipocytes. CONCLUSION: Short-term IA therapy could significantly ameliorate endothelial dysfunction induced by HFD, which may be partly due to attenuating inflammation of PCAT through inhibiting 5-LO pathway. PMID- 25131235 TI - Iloprost inhibits fracture repair in rats. AB - BACKGROUND: Previous studies have shown that prostaglandins (PGs) dramatically stimulate healing processes in bone. However, the effect of prostaglandin I2 (PGI2) on fracture healing remains unclear. To investigate the effect of PGI2, a study on fracture healing process in closed tibia fractures was designed. METHODS: Thirty-six Sprague-Dawley male rats were randomized into two groups. On the first day, their right tibias were fractured by three-point bending technique. The study group (n = 18) received a single injection of 10 ug/kg iloprost for 5 days, while the control group (n = 18) received saline solution in the same way. On the 7th, 14th and 28th days following the fracture, six rats were sacrificed and their right legs were harvested in each group. The progression of fracture healing was assessed for each specimen by the scores of radiography (by Lane-Sandhu) and histology (by Huo et al). RESULTS: On the 7th day, the radiographic and histologic scores were equal. On the 14th day radiographic total score was 6 and histologic total score was 23 in the iloprost group, whereas radiographic total score was 11 and histologic total score was 33 in the control group. On the 14th day radiographic and histologic scores were significantly decreased in the iloprost group compared to the control group (P < 0.05). On the 28th day radiographic total score was 12 and histologic total score was 37 in the iloprost group, whereas radiographic total score was 15 and histologic total score was 40 in the control group. On the 28th day although there was a decrease in radiographic and histologic scores of the iloprost group acording to control group, it was not statistically significant (P > 0.05). CONCLUSION: Iloprost delays fracture healing in early stage in rats. PMID- 25131236 TI - Effect and mechanism of tacrolimus on melanogenesis on A375 human melanoma cells. AB - BACKGROUND: Topical tacrolimus has been used for vitiligo as a common treatment option for more than ten years while the underlying mechanism is still uncertain. The aim of this study was to investigate the direct effects of tacrolimus on the melanogenesis and migration on human A375 melanoma cells. The expression of c-KIT mRNA and protein of human A375 cells were also investigated. METHODS: The cultured A375 human melanoma cells were randomly assigned to control and tacrolimus treatment groups (10, 10(2), 10(3) and 10(4) nmol/L). The cell proliferation was measured with Cell Counting Kit-8 assays. Melanin content was measured with NaOH method. Transwell migration assay was used to measure cell migration. The expression of c-KIT mRNA and protein were measured with real-time fluorescence quantitative polymerase chain reaction and immunohistochemistry respectively. RESULTS: The cell proliferation of the 10(3) and 10(4) nmol/L tacrolimus groups were significantly lower (0.666 +/- 0.062 and 0.496 +/- 0.038) as compared with the control (0.841 +/- 0.110, P < 0.05). The mean melanin content in all groups treated with different concentration of tacrolimus (10, 10(2), 10(3), 10(4) nmol/L) increased compared with the control group (P < 0.05). Dose-dependent increase in cell migration were seen in all tacrolimus-treated groups (P < 0.01). The expression of c-KIT mRNA level in A375 cells exposed to tacrolimus (10(3) and 10(4) nmol/L) had significantly increased by 3.03-fold and 3.19-fold respectively compared with the control (P < 0.05). CONCLUSIONS: Although tacrolimus had no effects on cell proliferation on A375 human melanoma cells, it could increase the melanin content and cell migration. The expression of c-KIT mRNA and protein increased dose-dependently in tacrolimus-treated groups as compared with the control. Our study demonstrated that tacrolimus could enhance the melanogenesis and cell migration on A375 cells. PMID- 25131237 TI - Reinnervation of hair cells by neural stem cell-derived neurons. AB - BACKGROUND: Replacement of spiral ganglion neurons would be one prioritized step in an attempt to restore sensory neuronal hearing loss. However, the possibility that transplanted neurons could regenerate new synaptic connections to hair cells has not been explored. The objective of this study was to test whether neural stem cell (NSC)-derived neurons can form synaptic connections with hair cells in vitro. METHODS: NSCs were mechanically separated from the hippocampus in SD rat embryos (E12-E14) and cultured in a serum-free medium containing basic fibroblast growth factor and epidermal growth factor. Rat NSCs were co-cultured with explants of cochlea sensory epithelia obtained from postnatal Day 3 rats under transway filter membrane. RESULTS: At Day 3, the NSCs began to show chemotactic differentiation and grew toward cochlea sensory epithelia. After 9-day co culture, neurites of NSC-derived neurons predominantly elongated toward hair cells. Immunohistochemical analyses revealed the fibers overlapped with synapsin and hair cells, indicating the formation of new synaptic connections. After 14 day culture, triple staining revealed the fibers overlapped with PSD95 (postsynaptic density) which is juxtaposed with CtBP2 (presynaptic vesicle), indicating the formation of new ribbon synapse. CONCLUSIONS: NSC-derived neurons can make synaptic connections with hair cells and provide a model for studying synaptic plasticity and regeneration. Whether the newly forming synapse is functional merits further electrophysiological study. PMID- 25131238 TI - Regulation of lovastatin on a key inflammation-related microRNA in myocardial cells. AB - BACKGROUND: Advances in the understanding of cardiovascular pathogenesis have highlighted that inflammation plays a central role in atherosclerotic coronary heart disease. Therefore, exploring pharmacologically based anti-inflammatory treatments to be used in cardiovascular therapeutics is worthwhile to promote the discovery of novel ways of treating cardiovascular disorders. METHODS: The myocardial cell line H9c2(2-1) was exposed to lipopolysaccharide (LPS) in culture and resulted in a cellular pro-inflammation status. miR-21 microRNA levels were detected using quantitative real-time polymerase chain reaction (Q-RT-PCR). The influence of lovastatin on miR-21 under normal and pro-inflammatory conditions was tested after being added to the cell culture mixture for 24 hours. Conditional gene function of two predicted cardiovascular system relevant downstream targets of miR-21, protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and signal transducer and activator of transcription 3 (STAT3), were analyzed with immunoblotting. RESULTS: Forty-eight hours of LPS treatment significantly increased the miR-21 to 170.71%+/- 34.32% of control levels (P = 0.002). Co-treatment with lovastatin for 24 hours before harvesting attenuated the up-regulation of miR-21 (P = 0.013). Twenty-four hours of lovastatin exposure up-regulated PPP1R3A to 143.85%+/- 21.89% of control levels in cardiomyocytes (P = 0.023). Lovastatin up-regulated the phosphorylation level of STAT3 compared to the background LPS pretreatment (P = 0.0077), this effect was significantly (P = 0.018) blunted when miR-21 was functionally inhibited. CONCLUSIONS: miR-21 plays a major role in the regulation of the cellular anti-inflammation effects of lovastatin. PMID- 25131239 TI - Comparison of the clinical and radiological outcomes following midvastus and medial parapatellar approaches for total knee arthroplasty: a meta-analysis. AB - BACKGROUND: Controversy still exists regarding whether medial parapatellar approach (MP) or midvastus approach (MV) is preferable in total knee arthroplasty (TKA) up to now. The aim of this meta-analysis was to compare the clinical and radiological outcomes following the MV or MP for TKA. METHODS: A comprehensive search of unrestricted-language literature of all studies comparing MP with MV was conducted through the electronic literature databases of PubMed, EMBASE, Cochrane Library, CNKI, VIP, and WANFANG. Retrieval time was from the time when databases were built to October 2013. Manual search of relevant trials, reviews, and related articles was also performed. Outcomes of interest included postoperative knee extensor and flexor function, postoperative pain, patella tilt, and complications. Relative risk (RR) and weighted mean differences (WMD) from each trial were pooled using random-effects or fixed-effects model depending on the heterogeneity of the included studies. A subgroup analysis or a sensitivity analysis was conducted to explore the potential source of heterogeneity when necessary. RESULTS: Twenty-one randomized controlled trials (RCTs) comprising 1 188 patients (1 450 knees) were eligible. Our results showed that MV was associated with better early postoperative extension (WMD = -1.26, 95% CI -2.36 to -0.16, P = 0.02) and flexion (WMD = 10.13, 95% CI 5.36 to 14.90, P < 0.01), less postoperative pain (WMD = -0.21, 95% CI -0.34 to -0.07, P = 0.002) , and no greater risk for complications than MP. The patella tilt did not differ significantly between the two groups (WMD = -0.70, 95% CI -1.94 to 0.54, P = 0.27). CONCLUSIONS: MV may be a better approach than MP, as it improves postoperative early joint function and decreases pain. Future multi-center randomized controlled studies with large sample sizes are required to verify the current findings. PMID- 25131240 TI - Prevalence of depression in coronary heart disease in China: a systematic review and meta-analysis. AB - BACKGROUND: Coronary heart diseases (CHD) have been identified as one of topmost diseases affecting the Chinese population. However, depression in CHD has not been reported and there are limited high quality empirical studies in China focused on the prevalence of the comorbidity. This study aimed to estimate the pooled prevalence of depression with CHD in China. METHODS: Systematic review and meta-analysis of published epidemiologic studies on the depression in CHD patients in China were conducted. The research findings dated before 30 September 2013 were obtained from Ovid Medline, EMBASE and two Chinese electronic publication libraries WANFANG and CNKI. We used "cardiovascular disease", "depression" and "China" as the search themes in Ovid Medline and EMBASE and "cardiovascular disease" and "depression" in WANFANG and CNKI. Random-effects meta-analysis was used to estimate the prevalence of depression in CHD patients. RESULTS: Twenty-seven studies were included in the review. Twenty-three studies had 5 236 participants who were hospitalized and four studies had 1 353 participants from community. The overall prevalence of depression in CHD from hospital was 51% (95% CI: 0.43, 0.58; I-squared = 97%, P = 0.000).The prevalence of depression in CHD from community ranged between 34.6% to 45.8%, and the severe depression was found ranging between 3.1% to 11.2%. CONCLUSIONS: On comparing data with other countries, the prevalence of depression in CHD among admitted patients in China was found to be high. The physicians and healthcare providers should pay more attention to the "physical-mental" health of the CHD patients. PMID- 25131241 TI - Mixed phenotype acute leukemia. AB - OBJECTIVE: To highlight the current understanding of mixed phenotype acute leukemia (MPAL). DATA SOURCES: We collected the relevant articles in PubMed (from 1985 to present), using the terms "mixed phenotype acute leukemia", "hybrid acute leukemia", "biphenotypic acute leukemia", and "mixed lineage leukemia". We also collected the relevant studies in WanFang Data base (from 2000 to present), using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia". STUDY SELECTION: We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version, with no limitation of research design. The duplicated articles are excluded. RESULTS: MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously. The clinical manifestations of MPAL are similar to other acute leukemias. The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 criteria are most widely used. MPAL does not have a standard therapy regimen. Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features, and also the experience of individual physician. The lack of effective treatment contributes to an undesirable prognosis. CONCLUSION: Our understanding about MPAL is still limited. The diagnostic criteria have not been unified. The treatment of MPAL remains to be investigated. The prognostic factor is largely unclear yet. A better diagnostic criteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis. PMID- 25131242 TI - Sphingosine Kinase-1/sphingosine 1-phosphate pathway in diabetic nephropathy. AB - OBJECTIVE: Diabetic nephropathy (DN) is the major cause of end-stage renal disease worldwide and its prevalence continues to increase. Currently, therapies for DN provide only partial renoprotection; hence new targets for therapeutic intervention need to be identified. In this review, we summarized the new target, sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway, explored its potential therapeutic role in the prevention and treatment of DN. DATA SOURCES: Most relevant articles were mainly identified by searching PubMed in English. STUDY SELECTION: Mainly original articles and critical review articles by major pioneer investigators in this field were selected to be reviewed. RESULTS: SphK1/S1P pathway can be activated by hyperglycemia, advanced glycation end products, and many pro-inflammatory cytokines, which leads to fibronectin, transforming growth factor-beta1 up-regulation and AP-1 activation. And then it could promote glomerular mesangial cells proliferation and extracellular matrix accumulation, mediating the initiation and progression of diabetic renal fibrosis. CONCLUSIONS: SphK1/S1P pathway is closely correlated with the pathogenesis of DN. The results suggest that SphK1/S1P pathway as a new target for clinically improving DN in future is of great prospect. PMID- 25131243 TI - Cardiorenal syndrome: pathophysiological mechanism, preclinical models, novel contributors and potential therapies. AB - OBJECTIVE: To review the current knowledge about the pathophysiological mechanisms, preclinical models, novel contributors and potential therapies of cardiorenal syndrome. DATA SOURCES: The literature concerning cardiorenal syndrome in this review was collected from PubMed published in English up to January 2014. STUDY SELECTION: Original articles and critical reviews related to cardiorenal syndrome were selected and carefully analyzed. RESULTS: Cardiorenal syndrome is a condition characterized by kidney and heart failure where failure of one organ worsens the function of the other thus further accelerating the progressive failure of both organs. The pathophysiology of cardiorenal syndrome is not fully understood, but may be caused by a complex combination of neurohormonal system activation, endothelial dysfunction, proteinuria, oxidative stress, uremic toxins and other factors. Managing cardiorenal syndrome is still a major therapeutic challenge in clinical practice because many of the drugs used to control heart failure can worsen renal function, and vice versa. Non dialyzable uremic toxins, such as indoxyl sulfate, causing detrimental effects on the heart and kidney as well as stimulation of inflammatory responses, may be an effective therapeutic target for cardiorenal syndrome. CONCLUSIONS: Suitable disease models of cardiorenal syndrome are urgently needed to investigate the pathophysiology and effective therapeutic approaches to the condition. Non dialyzable protein-bound uremic toxins that may have cardiac and renal effects may provide therapeutic benefit to cardiorenal syndrome patients. PMID- 25131244 TI - Predictors of anti-vascular endothelial growth factor treatment responses in macular edema following central vein occlusion. PMID- 25131245 TI - Neurological outcomes of patients admitted to the intensive care unit for cardiac arrest. PMID- 25131246 TI - Robotic and laparoscopic hybrid pancreaticoduodenectomy: surgical techniques and early outcomes. PMID- 25131247 TI - Pulmonary embolism with septicemia after N-butyl-2-cyanoacrylate injection for bleeding gastric varices. PMID- 25131248 TI - Extracorporeal membrane oxygenation as a platform for the management of massive hemoptysis caused by bronchial artery aneurysm. PMID- 25131249 TI - Aortic valve replacement for quadricuspid aortic valve with regurgitation and stenosis in a renal transplant recipient. PMID- 25131250 TI - Significance of ST-segment elevation in lead aVR. PMID- 25131251 TI - Caseous calcification of the mitral annulus: a rare variant of mitral annular calcification. PMID- 25131252 TI - Weaning method from mechanical ventilation, more computer or clinical perspective: who is helping whom truly? PMID- 25131253 TI - Treatment of coexisting bullous pemphigoid and psoriasis with triptergium wilfordii. PMID- 25131254 TI - Ruptured pancreatic desmoid tumor presenting as hemorrhagic shock: a rare cause of acute abdomen. PMID- 25131255 TI - Should radioactive iodine therapy be administrated in patient of papillary thyroid carcinoma? PMID- 25131256 TI - Severity stratification of aplastic anemia. PMID- 25131257 TI - Circulating miR-192 in liver fluke-associated cholangiocarcinoma patients: a prospective prognostic indicator. AB - BACKGROUND: This study aimed to investigate the miR-192 levels in patients' sera of liver fluke-associated cholangiocarcinoma (CCA) for a prospective prognostic indicator. METHODS: MicroRNA polymerase chain reaction (PCR) array was performed using pooled serum samples from 11 CCA patients and nine healthy subjects. Selected miRNAs were verified for the differential levels in both sera and tumor tissues (of patients and Opisthorchis viverrini (Ov)-induced CCA model) using TaqMan miRNA expression assay. RESULTS: Our results demonstrated that miR-192 was significantly higher in the serum of CCA patients than that in healthy subjects giving a sensitivity of 74% and specificity of 72% (area under the curve [AUC] = 0.803; 95% confidence interval [CI], 0.708-0.897, P < 0.0001). Serum miR-192 examined in Ov infected subjects and subjects with periductal fibrosis were increased but not statistically significantly when compared with healthy subjects. High levels of serum miR-192 were significantly correlated with lymph node metastasis (P = 0.047) and shorter survival compared with individuals with low levels of serum miR-192 (hazard ratio [HR] 2.076, 95% CI 1.004-4.291, P = 0.049). We also found that the expression levels of miR-192 appeared to be elevated in both CCA tissues of patients and in Ov-induced CCA tissues of a hamster model. CONCLUSIONS: This finding indicates that elevated levels of miR 192 may be involved in CCA genesis and have a potential utility as a noninvasive prognostic indicator for CCA patients. PMID- 25131258 TI - Influence of cultivar and ripening time on bioactive compounds and antioxidant properties in Cape gooseberry (Physalis peruviana L.). AB - BACKGROUND: Cape gooseberry (Physalis peruviana) is an exotic fruit highly valued for its organoleptic properties and bioactive compounds. Considering that the presence of phenolics and ascorbic acid could contribute to its functional capacity, it is important to investigate the quality parameters, bioactive contents and functional properties with respect to genotype and ripening time. In this study the genotype effect was evaluated in 15 cultivars for two different harvest times. Changes during maturation were recorded in two commercial cultivars within seven levels of maturity. RESULTS: Multivariate statistical analysis suggested that phenolic content and ORAC value were mainly affected by harvest time and that ascorbic acid content and DPPH level were mainly affected by genotype. In addition, acidity, phenolic content, ORAC value and inhibition of LDL oxidation decreased with maturity, but soluble solids content, ascorbic acid content, beta-carotene content and DPPH-scavenging activity were higher in mature fruits. CONCLUSION: The phenolic content, ascorbic acid content and antioxidant properties of Cape gooseberry fruit were strongly affected by cultivar, harvest time and maturity state. Consequently, the harvest time must be scheduled carefully to gain the highest proportion of bioactive compounds according to the specific cultivar and the environment where it is grown. PMID- 25131259 TI - Solvent induced helical aggregation in the self-assembly of cholesterol tailed platinum complexes. AB - Three alkynylplatinum(ii) bipyridyl complexes in which two cholesterol groups are combined with a bipyridyl group via alkyl chains and amido bonds were designed and synthesized. The complexes have different lengths of ethylene glycol chains at the para-position of 1-phenylethyne. All three complexes can self-assemble to gel networks in DMSO, while only the morphology of 1a without an ether chain shows a well-defined right-handed helical structure in layer packing mode. However, 1c with long ethylene glycol chains forms perfect regular left-handed helical structures in aqueous ethanol solution while the volume percentage of water is less than 5% (v/v). As the ratio of water increases, the chirality changes from a left-handed helix to a right-handed helix and the packing mode alters from a monolayer structure to a hexagonal structure. As the ratio of water further increases to greater than 50% (v/v), the structure of the assembly finally transforms into bilayer vesicles. The process of the morphology transition is traced by circular dichroism spectra, powder X-ray diffraction, SEM and TEM images. The result indicates that a polar solvent (water) acts as a trigger to change the self-assembly of the chiral structures of the complex due to the strong hydrophobic interaction between cholesterol groups and the balance of the hydrophobicity and hydrophilicity of the solvent environment. PMID- 25131260 TI - The small GTPases regulate HMC05-induced NQO-1 expression with an antioxidant effect in smooth muscle cells. AB - Recently, Banhabackchulchunmatang (HMC05) has been implicated as a preventive and/or therapeutic candidate for cardiovascular diseases due to its inhibition of atherosclerosis lesions and its reduction of neointima formation. Knowledge of the mechanism of HMC05 in smooth muscle cells (SMC) is limited. However, SMC may be a potential target for HMC05 therapy because they are supported by the HMC05 mediated preservation of medial smooth muscle cell layers in pathogenic progression. Therefore, in the present study, we hypothesized that the effect of HMC05 is associated with reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H):quinone oxidoreductase-1 (NQO-1) gene regulation, which precipitates an antioxidant effect in SMC. HMC05 significantly increased NQO-1 gene expression in a dose- and time-dependent manner. The reactive oxygen species-mediated toxicity that was generated by xanthine/xanthine oxidase was suppressed by HMC05. The knockdown of the NQO-1 gene abrogated the HMC05-mediated cytoprotection. Interestingly, pretreatment with a chemical inhibitor of geranylgeranyl transferase 1 or farnesyl transferase abolished the NQO-1 gene induction and cytoprotection by HMC05. The transfection of dominant negative RhoA or Ras suppressed HMC05-induced gene expression. Berberine and hesperidin, which are found in large quantities in HMC05, also induced NQO-1 gene expression. Taken together, this is the first study to demonstrate that HMC05 is efficacious in protection against oxidative stress through NOQ-1 gene induction via the regulation of RhoA and/or Ras, and that berberine and hesperidin are major components of NQO-1 gene induction. This study provides mechanistic targets of HMC05 in reducing atherosclerotic lesions in atherosclerosis. PMID- 25131261 TI - Thyroarytenoid cross-innervation by the external branch of the superior laryngeal nerve in the porcine model. AB - OBJECTIVES/HYPOTHESIS: Cross-innervation patterns to the thyroarytenoid (TA) muscle have long been sought after. We have identified in the porcine model, cross-innervation by way of the external branch of the superior laryngeal nerve (eSLN). STUDY DESIGN: Experimental study. METHODS: TA contraction was electromyographically recorded when electrically stimulating the eSLN in six porcine necks. The recurrent laryngeal nerve (RLN) was subsequently transected. The insertion of the cricothyroid (CT) muscle on the cricoid was then subsequently removed as well. RESULTS: Stimulation of the eSLN rendered a response from the TA muscle in 6/6 subject necks, with a mean latency of 2.76 msec. TA muscle contraction by way of eSLN stimulation persisted after the RLN was transected and after CT insertion release. CONCLUSIONS: The TA muscle is directly cross-innervated by a branch of the eSLN in the porcine model. This finding may have implications regarding possible future laryngeal pacing strategies and could be a target nerve for rehabilitation. PMID- 25131263 TI - Do the treasures of 'big data' combined with behavioural intervention therapies contain the key to the mystery of large psychiatric issues? PMID- 25131262 TI - Association of daunorubicin to a lipid nanoemulsion that binds to low-density lipoprotein receptors enhances the antitumour action and decreases the toxicity of the drug in melanoma-bearing mice. AB - OBJECTIVES: To test the toxicity and antitumoral activity of the compound N-oleyl daunorubicin (oDNR) with a cholesterol-rich nanoemulsion (LDE) formulation. METHODS: LDE-oDNR was prepared by high-pressure homogenisation of lipid mixtures. B16F10 melanoma cells and NIH/3T3 fibroblasts were used for cytotoxicity tests. The maximum tolerated dose (MTD) of both commercial and LDE-oDNR was determined in mice, and melanoma-bearing mice were used for the antitumoral activity tests. KEY FINDINGS: CC50 for LDE-oDNR and DNR in melanoma cells were 200 MUm and 15 MUm, respectively, but LDE-oDNR was less toxic against fibroblasts than DNR. MTD for LDE-oDNR was 65-fold higher than commercial DNR. In tumour-bearing mice, LDE oDNR (7.5 MUmol/kg) reduced tumour growth by 59 +/- 2%, whereas the reduction by DNR was only 23 +/- 2%. LDE-oDNR increased survival rates (P < 0.05), which was not achieved by DNR treatment. The number of mice with metastasis was only 30% in LDE-oDNR-treated mice, compared with 82% under DNR treatment. By flow cytometry, there were 9% viable cells in tumours of animals treated with LDE-oDNR compared with 27% in DNR-treated animals. Less haematological toxicity was observed in LDE oDNR-treated mice. CONCLUSIONS: Compared with DNR, LDE-oDNR improved tumour growth inhibition and survival rates with pronouncedly less toxicity, and thus may become a new tool for cancer treatment. PMID- 25131264 TI - Repeated formaldehyde inhalation impaired olfactory function and changed SNAP25 proteins in olfactory bulb. AB - BACKGROUND: Formaldehyde inhalation exposure, which can occur through occupational exposure, can lead to sensory irritation, neurotoxicity, mood disorders, and learning and memory impairment. However, its influence on olfactory function is unclear. OBJECTIVES: To investigate the mechanism and the effect of repeated formaldehyde inhalation exposure on olfactory function. METHODS: Rats were treated with formaldehyde inhalation (13.5+/-1.5 ppm, twice 30 minutes/day) for 14 days. Buried food pellet and locomotive activity tests were used to detect olfactory function and locomotion. Western blots were used to evaluate synaptosomal-associated protein 25 (SNAP25) protein levels in the olfactory bulb (OB) lysate and synaptosome, as well as mature and immature olfactory sensory neuron markers, olfactory marker protein (OMP), and Tuj-1. Real time polymerase chain reaction (PCR) was used to detect SNAP25 mRNA amounts. RESULTS: Repeated formaldehyde inhalation exposure impaired olfactory function, whereas locomotive activities were unaffected. SNAP25 protein decreased significantly in the OB, but not in the occipital lobe. SNAP25 also decreased in the OB synaptosome when synaptophysin did not change after formaldehyde treatment. mRNA levels of SNAP25A and SNAP25B were unaffected. Mature and immature olfactory sensory neuron marker, OMP, and Tuj-1, did not change after formaldehyde treatment. CONCLUSION: Repeated formaldehyde exposure impaired olfactory function by disturbing SNAP25 protein in the OB. PMID- 25131268 TI - Seventy-five years completed and thirty-six to go! PMID- 25131265 TI - Uses of cancer registries for public health and clinical research in Europe: Results of the European Network of Cancer Registries survey among 161 population based cancer registries during 2010-2012. AB - AIM: To provide insight into cancer registration coverage, data access and use in Europe. This contributes to data and infrastructure harmonisation and will foster a more prominent role of cancer registries (CRs) within public health, clinical policy and cancer research, whether within or outside the European Research Area. METHODS: During 2010-12 an extensive survey of cancer registration practices and data use was conducted among 161 population-based CRs across Europe. Responding registries (66%) operated in 33 countries, including 23 with national coverage. RESULTS: Population-based oncological surveillance started during the 1940-50s in the northwest of Europe and from the 1970s to 1990s in other regions. The European Union (EU) protection regulations affected data access, especially in Germany and France, but less in the Netherlands or Belgium. Regular reports were produced by CRs on incidence rates (95%), survival (60%) and stage for selected tumours (80%). Evaluation of cancer control and quality of care remained modest except in a few dedicated CRs. Variables evaluated were support of clinical audits, monitoring adherence to clinical guidelines, improvement of cancer care and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools was only occasional. CONCLUSION: Most population-based CRs are well equipped for strengthening cancer surveillance across Europe. Data quality and intensity of use depend on the role the cancer registry plays in the politico, oncomedical and public health setting within the country. Standard registration methodology could therefore not be translated to equivalent advances in cancer prevention and mass screening, quality of care, translational research of prognosis and survivorship across Europe. Further European collaboration remains essential to ensure access to data and comparability of the results. PMID- 25131266 TI - Surgical site infection after total en bloc spondylectomy: risk factors and the preventive new technology. AB - BACKGROUND CONTEXT: Surgical site infection (SSI) associated with instruments remains a serious and common complication in patients who undergo total en bloc spondylectomy (TES). It is very important that the risk factors for SSI are known to prevent it. PURPOSE: The purpose of the study was to identify independent risk factors for SSI after TES and evaluate the positive effect of iodine-supported spinal instruments in the prevention of SSI after TES. STUDY DESIGN: This is a retrospective clinical study. PATIENT SAMPLE: One hundred twenty-five patients who underwent TES for vertebral tumor were evaluated. OUTCOME MEASURES: Incidence rate of SSI, risk factors for SSI after TES, and safety of iodine-supported spinal instruments were the outcome measures. METHODS: Risk factors for SSI were analyzed using logistic regression. In recent 69 patients with iodine-supported spinal instruments, the thyroid hormone levels in the blood were examined to confirm if iodine from the implant influenced thyroid function. Postoperative radiological evaluations were performed regularly. RESULTS: The rate of SSI was 6.4% (8/125 patients). By multivariate logistic regression, combined anterior and posterior approach and nonuse of iodine-supported spinal instruments were associated with an increased risk of SSI. The rate of SSI without iodine supported spinal instruments was 12.5%, whereas the rate with iodine-supported spinal instruments was 1.4%. This difference was statistically significant. There were no detected abnormalities of thyroid gland function with the use of iodine supported instruments. Among the 69 patients with iodine-supported spinal instruments, 2 patients required additional surgery because of instrument failure. However, there were no obvious involvements with the use of iodine supported spinal instruments. CONCLUSIONS: This study identified combined anterior and posterior approach and nonuse of iodine-supported spinal instruments to be independent risk factors for SSI after TES. Iodine-supported spinal instrument was extremely effective for prevention of SSI in patients with compromised status, and it had no detection of cytotoxic or adverse effects on the patients. PMID- 25131271 TI - Third-grade retention and reading achievement in Texas: a nine year panel study. AB - The academic performance of over 38,000 Texas students who failed the state's 1994 reading test was examined through their sophomore year in high school. Propensity score matching resulted in strata with retained and promoted students of comparable observed characteristics. Reading scores were analyzed using a two level hierarchical linear model. Same grade comparisons show that third graders failing the state-mandated reading test who repeated the grade consistently outperformed in later grades the socially promoted children who also failed the third grade test. Additional analyses indicate that alternative explanations for the findings such as omitted variables, regression to the mean, differential panel attrition and cohort effects are not supported. The results are consistent with findings from other recent studies which suggest that grade retention in third grade may help increase student achievement. PMID- 25131270 TI - A neural mass model based on single cell dynamics to model pathophysiology. AB - Neural mass models are successful in modeling brain rhythms as observed in macroscopic measurements such as the electroencephalogram (EEG). While the synaptic current is explicitly modeled in current models, the single cell electrophysiology is not taken into account. To allow for investigations of the effects of channel pathologies, channel blockers and ion concentrations on macroscopic activity, we formulate neural mass equations explicitly incorporating the single cell dynamics by using a bottom-up approach. The mean and variance of the firing rate and synaptic input distributions are modeled. The firing rate curve (F(I)-curve) is used as link between the single cell and macroscopic dynamics. We show that this model accurately reproduces the behavior of two populations of synaptically connected Hodgkin-Huxley neurons, also in non-steady state. PMID- 25131272 TI - Understanding the links between education and smoking. AB - This study extends the theoretical and empirical literature on the relationship between education and smoking by focusing on the life course links between experiences from adolescence and health outcomes in adulthood. Differences in smoking by completed education are apparent at ages 12-18, long before that education is acquired. I use characteristics from the teenage years, including social networks, future expectations, and school experiences measured before the start of smoking regularly to predict smoking in adulthood. Results show that school policies, peers, and youths' mortality expectations predict smoking in adulthood but that college aspirations and analytical skills do not. I also show that smoking status at age 16 predicts both completed education and adult smoking, controlling for an extensive set of covariates. Overall, educational inequalities in smoking are better understood as a bundling of advantageous statuses that develops in childhood, rather than the effect of education producing better health. PMID- 25131273 TI - Tracing the cigarette epidemic: an age-period-cohort study of education, gender and smoking using a pseudo-panel approach. AB - This study examined if temporal variations in daily cigarette smoking and never smoking among groups with different levels of education fit the pattern proposed by the theory of diffusion of innovations (TDI), while taking into account the separate effects of age, period and birth cohort (APC). Aggregated data from nationally representative interview surveys from Norway from 1976 to 2010 was used to calculate probabilities of smoking using an APC approach in which the period variable was normalized to pick up short term cyclical effects. Results showed that educational differences in smoking over time were more strongly determined by birth cohort membership than variations in smoking behavior across the life course. The probability of daily smoking decreased faster across cohorts among higher compared to lower educated. In contrast, the change in probability of never having smoked across cohorts was similar in the two education groups, but stronger among men compared to women. Moreover, educational differences in both daily and never smoking increased among early cohorts and leveled off among late cohorts. The results emphasizes the importance of birth cohort for social change and are consistent with TDI, which posits that smoking behavior diffuse through the social structure over time. PMID- 25131274 TI - Life satisfaction across nations: the effects of women's political status and public priorities. AB - Feminist scholars suggest that improving the quality of life of individuals living in nations around the world may be more readily achieved by increasing women's political power and by reorienting public-policy priorities, than by focusing primarily on economic growth. These considerations raise the question of which characteristics of societies are associated with the quality of life of the people in those societies. Here, we address this issue empirically by statistically analyzing cross-national data. We assess the effects of gender equality in the political sphere, as well as a variety of other factors, on the subjective well-being of nations, as indicated by average self-reported levels of life satisfaction. We find that people report the highest levels of life satisfaction in nations where women have greater political representation, where military spending is low, and where health care spending is high, controlling for a variety of other factors. GDP per capita, urbanization, and natural resource exploitation are not clearly associated with life satisfaction. These findings suggest that nations may be able to improve the subjective quality of life of people without increasing material wealth or natural resource consumption by increasing gender equality in politics and changing public spending priorities. PMID- 25131275 TI - Is the social volcano still dormant? Trends in Chinese attitudes toward inequality. AB - Data from two China national surveys, in 2004 and 2009, focusing on popular attitudes toward current inequalities and mobility opportunities, are compared to examine two key questions: (1) Did the continued rise in income gaps and the impact within China of the global financial crisis lead to rising popular anger about the unfairness of current inequality patterns in 2009? and (2) Did the social contours of attitudes toward current inequalities shift over the five years between surveys? Through systematic comparisons of data from both surveys, we conclude that there is no general increase in anger about inequalities in the 2009 survey, and that the predictors of variations in these attitudes had changed relatively little, with the unexpectedly positive views of villagers still visible in 2009, although a bit muted. Trends in Chinese society between 2004 and 2009, and in the personal experience of survey respondents, are used to explain why popular acceptance of current inequalities remains widespread, despite continuing increases in China's income gaps. PMID- 25131277 TI - Social welfare support and homicide: longitudinal analyses of European countries from 1994 to 2010. AB - The purpose of this research is to explore the extent to which retrenchment in welfare support is related to homicide trends across European countries between 1994 and 2010. Using a longitudinal decomposition design that allows for stronger causal inferences compared to typical cross-sectional designs, we examine these potential linkages between social support spending and homicide with data collected from a heterogeneous sample of European nations, including twenty Western nations and nine less frequently analyzed East-Central nations, during recent years in which European nations generally witnessed substantial changes in homicide rates as well as both economic prosperity and fiscal crisis. Results suggest that even incremental, short-term changes in welfare support spending are associated with short-term reductions in homicide-specifically, impacting homicide rates within two to three years for this sample of European nations. PMID- 25131276 TI - Intimate partner victimization, poor relationship quality, and depressive symptoms during young adulthood. AB - Using longitudinal data from the Toledo Adolescent Relationships Study (n = 927), we examined physical victimization, poor quality, and depression among young adults in casually dating, exclusively dating, cohabiting, and marital relationships. In multivariate models, victimization was a risk factor for depression with the inclusion of prior depression, family factors reflecting the intergenerational transmission of violence, sociodemographic background, and relationship characteristics including union status. With the inclusion of indicators of poor relational quality, victimization was not a significant predictor of depression. Arguing and poor communication influenced victimization and depression. Associations between victimization and depression did not differ by gender, nor were the effects of poor quality on depression conditional on gender. Thus, victimization occurs within relationships characterized by a range of negative dynamics. Multifaceted relationship-centered prevention efforts are more useful than focusing only on the use of aggression with a partner. PMID- 25131278 TI - Homonegativity among first and second generation migrants in Europe: the interplay of time trends, origin, destination and religion. AB - Previous studies reported declining disapproval of homosexuality in Europe but have simultaneously identified the decelerating effect of religiosity and the higher disapproval of homosexuality among migrants. In this paper, we address disapproval of homosexuality among first- and second-generation migrants in Europe by assessing (1) period and cohort changes, (2) origin and destination country influences and (3) the role of religiosity. We develop a specific cross classified multilevel design enabling us to simultaneously examine these influences. We test hypotheses using a subsample of the European Social Survey (ESS), containing 19,878 first and second generation migrants. The analyses lead to three important conclusions. Firstly, disapproval of homosexuality is declining both over time and across cohorts. Secondly, migrants conform to levels of disapproval of homosexuality among natives in the destination country, and this explains the decline among migrants over time. Thirdly, religion has a multi faceted influence on levels of disapproval of homosexuality among migrants. PMID- 25131279 TI - College quality and hourly wages: evidence from the self-revelation model, sibling models and instrumental variables. AB - This paper addresses the recent discussion on confounding in the returns to college quality literature using the Norwegian case. The main advantage of studying Norway is the quality of the data. Norwegian administrative data provide information on college applications, family relations and a rich set of control variables for all Norwegian citizens applying to college between 1997 and 2004 (N = 141,319) and their succeeding wages between 2003 and 2010 (676,079 person-year observations). With these data, this paper uses a subset of the models that have rendered mixed findings in the literature in order to investigate to what extent confounding biases the returns to college quality. I compare estimates obtained using standard regression models to estimates obtained using the self-revelation model of Dale and Krueger (2002), a sibling fixed effects model and the instrumental variable model used by Long (2008). Using these methods, I consistently find increasing returns to college quality over the course of students' work careers, with positive returns only later in students' work careers. I conclude that the standard regression estimate provides a reasonable estimate of the returns to college quality. PMID- 25131280 TI - Identifying predictors of survey mode preference. AB - To increase the likelihood of response, many survey organizations attempt to provide sample members with a mode they are thought to prefer. Mode assignment is typically based on conventional wisdom or results from mode choice studies that presented only limited options. In this paper we draw heavily on research and theory from the mode effects and the survey participation literatures to develop a framework for understanding what characteristics should predict mode preferences. We then test these characteristics using data from two different surveys. We find that measures of familiarity with and access to a mode are the strongest predictors of mode preference and measures of safety concerns, physical abilities, and normative concerns are unexpectedly weak predictors. Our findings suggest that variables that may exist on sample frames can be used to inform the assignment of "preferred" modes to sample members. PMID- 25131281 TI - Abortion attitudes in context: a multidimensional vignette approach. AB - The effects of relationship status, rationale for considering abortion (life circumstance versus health issue), and the male partner's wishes on abortion attitudes were examined using a multiple-segment factorial vignette with a probability sample of 532 Kentucky households. Respondents expressed strong opinions in the absence of contextual details, yet many shifted the direction of their strongly-held positions once contextual information was revealed that challenged their initial assumptions. Results confirm and extend prior research by indicating that attitudes are strongly held but are simultaneously highly responsive to context. The validity of surveys and polls that attempt to measure global attitudes toward abortion, such as pro-choice versus pro-life, in the absence of contextual details is therefore questioned. The full context of one's life and situation is weighed in the abortion decision-making process, and our findings indicate that attitudes toward abortion are largely responsive and reflective of that context as well. PMID- 25131282 TI - Intelligence and childlessness. AB - Demographers debate why people have children in advanced industrial societies where children are net economic costs. From an evolutionary perspective, however, the important question is why some individuals choose not to have children. Recent theoretical developments in evolutionary psychology suggest that more intelligent individuals may be more likely to prefer to remain childless than less intelligent individuals. Analyses of the National Child Development Study show that more intelligent men and women express preference to remain childless early in their reproductive careers, but only more intelligent women (not more intelligent men) are more likely to remain childless by the end of their reproductive careers. Controlling for education and earnings does not at all attenuate the association between childhood general intelligence and lifetime childlessness among women. One-standard-deviation increase in childhood general intelligence (15 IQ points) decreases women's odds of parenthood by 21-25%. Because women have a greater impact on the average intelligence of future generations, the dysgenic fertility among women is predicted to lead to a decline in the average intelligence of the population in advanced industrial nations. PMID- 25131283 TI - When do doctors follow patients' orders? Organizational mechanisms of physician influence. AB - Physicians, like other professionals, are expected to draw from specialized knowledge while remaining receptive to clients' requests. Using nationally representative U.S. survey data from the Community Tracking Study, this paper examines the degree to which physicians are influenced by patients' requests, and how physicians' workplaces may mediate acquiescence rates through three mechanisms: constraints, protection, and incentives. We find that, based on physicians' reports of their responses to patients' suggestions, patient influence is rare. This influence is least likely to be felt in large workplaces, such as large private practices, hospitals, and medical schools. We find that the protection and incentives mechanisms mediate the relationship between workplace types and physician acquiescence but more prescriptive measures such as guidelines and formularies do not affect acquiescence. We discuss these findings in light of the ongoing changes in the structure of medicine. PMID- 25131284 TI - NIMBYism - a re-examination of the phenomenon. AB - NIMBYism is the idea that citizens will oppose the siting of facilities in their neighborhood for selfish reasons. Using a new treatment - type of facility rather than geographical proximity to a particular site - the paper explores two rarely researched manifestations of NIMBYism: that people are so sensitive to nuisances that they oppose the siting of all facility types in their neighborhood; and that people will adjust motivations for resistance to appear public minded. Results from both observational and experimental studies support the basic claims of NIMBYism. PMID- 25131285 TI - The consequences of unrealized occupational goals in the transition to adulthood. AB - Do unmet occupational goals have negative consequences for well-being? Several social-psychological theories posit that aspirations become standards against which individuals judge themselves, thereby decreasing well-being when unmet. Yet other evidence points to young adults' goal flexibility and resilience, suggesting unmet aspirations may not affect well-being. This paper tests these alternatives using data from the National Longitudinal Study of Youth 1979 (N = 9016) and the National Educational Longitudinal Study of 1988 (N = 10,547) to examine whether the degree of match between adolescent occupational aspirations (NLSY) and expectations (NELS) and later attainment affect job satisfaction and depression. This paper also examines gender differences in the cost to unmet goals. Findings reveal a cost to falling short of one's occupational goals, manifested in more depressive symptoms for men in the older cohort, and lower job satisfaction for both men and women across two cohorts born approximately 14 years apart. PMID- 25131286 TI - The misunderstood consequences of Shelley v. Kraemer. AB - Shelley v. Kraemer (1948) was a landmark civil rights ruling, in which the Supreme Court held that private racial covenants could not be enforced by the state to evict black buyers of "restricted" homes. Fair housing scholars have generally dismissed or downplayed the practical effects of Shelley, since other forms of housing discrimination remained very powerful. Using spatial lag models and detailed geographic data on the location of covenants and patterns of intra urban black migration, we compare the role of Shelley with other forces shaping mid-century neighborhood change. We find that Shelley precipitated white-to-black neighborhood transitions after 1948 and changed the nature of the dual housing market in important ways. We also show that increased black mobility produced a sharp increase in intra-black economic segregation during the 1950s and 1960s. PMID- 25131287 TI - Friendship networks and the social structure of opportunities for contact and interaction. AB - This paper explores the Partnermarktsurvey to analyze how the size and composition of individuals' friendship networks are associated with the opportunities for contact and interaction provided by individuals' immediate social environment. The size and composition of individuals' social environment are strongly reflected in the size and composition of their network of friends. Several properties of an individual's foci of activity help to transform mere contacts into opportunities for interaction. The paper suggests to combine macro structural theory with micro-sociological theories about action and social capital. PMID- 25131288 TI - Political polarization on support for government spending on environmental protection in the USA, 1974-2012. AB - Since the early 1990s, the American conservative movement has become increasingly hostile toward environmental protection and Congressional Republicans have become increasingly anti-environmental in their voting records. Party sorting theory holds that such political polarization among elites will likely extend to the general public. Analyzing General Social Survey data from 1974 to 2012, we examine whether political polarization has occurred on support for government spending on environmental protection over this time period in the US general public. We find that there has been significant partisan and ideological polarization on support for environmental spending since 1992-consistent with the expectations of party sorting theory. This political polarization on environmental concern in the general public will likely endure save for political convergence on environmental concern among elites in the near future. Such polarization likely will inhibit the further development and implementation of environmental policy and the diffusion of environmentally friendly behaviors. PMID- 25131289 TI - The dynamic relationships between union dissolution and women's employment: a life-history analysis of 16 countries. AB - The specialization theory from Gary Becker is often used to explain the effect of women's work on the risk of divorce. The main argument is that women with little work experience have higher economic costs to exit marriage. Using the Fertility and Family Surveys, we test for 16 countries to what extent women's employment increases the risk of separation. We also more directly examine the role of economic exit costs in separation by investigating the effect of separated women's work history during the union on women's post-separation employment. The results imply that Becker was right to some extent, especially in contexts with little female employment support. However, in settings where women's employment opportunities are more ample, sociological or psychological theories have probably more explanatory power to explain the causes and consequences of union dissolution. PMID- 25131290 TI - Predictors of self-protective behaviors in non-sexual violent encounters: the role of victim sex in understanding resistance. AB - Self-protective behaviors are actions that victims take in a violent encounter to thwart the attack or avoid/minimize injury. This study examines the predictors of self-protective behaviors in non-sexual assault incidents with a particular focus on how the sex of the victim may moderate these conclusions. Non-sexual assault incidents in the National Crime Victimization Survey were analyzed (n=16,309) and four categories of self-protective behaviors were regressed on a variety of predictors using multivariate probit models. A variety of pre-assault factors (e.g., demographic characteristics), situational characteristics (e.g., location of assault), and the relationship between the victim and offender are associated with the use of resistance. Situational characteristics emerged as the most consistent and strongest predictors of self-protective behaviors. There was little evidence to suggest that separate models for male and female victims were warranted. PMID- 25131291 TI - Twelve-year survey (2001-2012) of the antimicrobial susceptibility of Streptococcus pneumoniae isolates from otorhinolaryngology clinics in Miyagi Prefecture, Japan. AB - INTRODUCTION: Streptococcus pneumoniae is one of the most common bacteria causing otorhinolaryngological infections, such as acute otitis media and upper respiratory tract infection. Our group surveyed the drug susceptibility profile of S. pneumoniae isolates from otorhinolaryngology patients. MATERIALS AND METHODS: A total of 41,069 S. pneumoniae isolates were detected at Miyagi Medical Association Health Center between May 2001 and December 2012. Specimens were obtained from patients at 40 otorhinolaryngology outpatient clinics in Miyagi Prefecture, Japan. The minimum inhibitory concentrations (MICs) of 8 antimicrobial agents were measured using the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines. RESULTS: In children aged 0-2 years old, the MIC50 values of penicillins decreased after 2010 (PCG: 1 MUg/ml (2010) to 0.06 MUg/ml (2012); ABPC: 1 MUg/ml (2010) to 0.25 MUg/ml (2012)). The prevalence of penicillin-resistant S. pneumoniae (PRSP) decreased from 35.2% (2010) to 14.6% (2012) in rhinorrhea specimens and from 43.4% (2010) to 14.3% (2012) in otorrhea specimens. Susceptibility to cephems (ceftriaxone and cefditoren) and carbapenems (panipenem) also showed improvement after 2010. For macrolides (clarithromycin) and lincosamides (clindamycin), MIC50 values increased in all age groups during the study period, and a high level of resistance was seen until 2012. There were no marked changes of susceptibility to fluoroquinolones (LVFX) during the study period. CONCLUSION: Improvement of susceptibility of S. pneumoniae to beta-lactams occurred after 2010 in Miyagi Prefecture, Japan. PMID- 25131292 TI - Post-marketing safety and effectiveness evaluation of the intravenous anti influenza neuraminidase inhibitor peramivir (I): a drug use investigation. AB - Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. We conducted a drug use investigation of peramivir from October 2010 to February 2012 and evaluated its safety and effectiveness under routine clinical settings. We collected data of 1309 patients from 189 facilities across Japan and examined safety in 1174 patients and effectiveness in 1158 patients. In total, 143 adverse events were observed with an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87% (22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR was reported as serious. ADR onset was within 3 days after the start of peramivir administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither patient characteristics nor treatment factors appeared to significantly affect drug safety. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. The present study demonstrates the safety and effectiveness of peramivir under routine clinical settings. PMID- 25131293 TI - Helicobacter cinaedi kidney cyst infection and bacteremia in a patient with autosomal dominant polycystic kidney disease. AB - A 48-year-old man with autosomal dominant polycystic kidney disease (ADPKD) was admitted to our hospital with a 5-day history of lower right back pain, high grade fever, and arthralgia. He was diagnosed with right kidney cyst infection and bacteremia due to Helicobacter cinaedi (H. cinaedi) based on these symptoms, highly elevated CRP (32.25 mg/dL), abdominal magnetic resonance imaging findings, and the identification of H. cinaedi from blood cultures using PCR and sequence analysis of the 16S ribosomal DNA gene. Intravenous cefotaxime 0.5 g twice daily followed by meropenem 0.5 g twice daily and ciprofloxacin 200 mg twice daily were partially effective; oral doxycycline added at 200 mg/day finally eradicated the infection. Total duration of antimicrobial therapy was 9 weeks. H. cinaedi infections typically present as bacteremia with or without cellulitis in immunocompromised patients such as those with AIDS or malignant disease. To our knowledge, this is the first report describing an ADPKD patient with H. cinaedi cyst infection. Although H. cinaedi infections are increasingly recognized, even in immunocompetent subjects, numerous cases may still be overlooked given that this bacterium is slow-growing, and is difficult to culture, be Gram-stained, and identify on phenotypic tests. Consideration of this bacterium as a possible pathogen and sufficient duration of incubation with molecular testing are necessary in treating ADPKD patients with cyst infection. PMID- 25131294 TI - First report of spondylodiscitis due to vancomycin heteroresistant Staphylococcus capitis in immunocompetent host. AB - We report a successfully treated case of spondylodiscitis and bloodstream infection due to vancomycin heteroresistant Staphylococcus capitis, in an adult immunocompetent patient with multiple antibiotics intolerance. S. capitis is rarely involved in osteomyelitis and, to our knowledge, this is the first report of vancomycin heteroresistance phenomenon in an S. capitis strain causing spondylodiscitis. PMID- 25131295 TI - Two types of genetic carrier, the IncP genomic island and the novel IncP-1beta plasmid, for the aac(2')-IIa gene that confers kasugamycin resistance in Acidovorax avenae ssp. avenae. AB - A unique aminoglycoside antibiotic, kasugamycin (KSM), has been used to control many plant bacterial and fungal diseases in several countries. The emergence of KSM-resistant Acidovorax avenae ssp. avenae and Burkholderia glumae, which cause rice bacterial brown stripe and rice bacterial grain and seedling rot, respectively, is a serious threat for the effective control of these diseases. Previously, we have identified the aac(2')-IIa gene, encoding a KSM 2'-N acetyltransferase, from both KSM-resistant pathogens. Although all KSM-resistant isolates from both species possess the aac(2')-IIa gene, only A. avenae strain 83 showed higher resistance than other strains. In this research, kinetic analysis indicates that an amino acid substitution from serine to threonine at position 146 of AAC(2')-IIa in strain 83 is not involved in this increased resistance. Whole draft genome analysis of A. avenae 83 shows that the aac(2')-IIa gene is carried by the novel IncP-1beta plasmid pAAA83, whereas the genetic carrier of other strains, the IncP genomic island, is inserted into their chromosomes. The difference in the nucleotides of the promoter region of aac(2')-IIa between strain 83 and other strains indicates an additional transcription start site and results in the increased transcription of aac(2')-IIa in strain 83. Moreover, biological characterization of pAAA83 demonstrates that it can be transferred by conjugation and maintained in the host cells. These results demonstrate that acquisition of the aac(2')-IIa gene takes place in at least two ways and that the gene module, which includes aac(2')-IIa and the downstream gene, may be an important unit for the dissemination of antibiotic resistance. PMID- 25131296 TI - Response. PMID- 25131297 TI - Vmp1 regulates PtdIns3P signaling during autophagosome formation in Dictyostelium discoideum. AB - Generation and turnover of phosphatidylinositol 3-phosphate (PtdIns3P) signaling is essential for autophagosome formation and other membrane traffic processes. In both Dictyostelium discoideum and mammalian cells, autophagosomes are formed from specialized regions of the endoplasmic reticulum (ER), called omegasomes, which are enriched in the signaling lipid PtdIns3P. Vacuole membrane protein 1 (Vmp1) is a multispanning membrane protein localized at the ER that is required for autophagosome formation. There are conflicting reports in the literature as to whether Vmp1 is strictly required or not for autophagy-related PtdIns3P signaling and its hierarchical relationship with Atg1 and PI3K. We have now addressed these questions in the Dictyostelium model. We show that Dictyostelium cells lacking Vmp1 have elevated and aberrant PtdIns3P signaling on the ER, resulting in an increased and persistent recruitment of Atg18 and other autophagic proteins. This indicates that Vmp1 is not strictly essential for the generation of PtdIns3P signaling but rather suggests a role in the correct turnover or modulation of this signaling. Of interest, these PtdIns3P-enriched regions of the ER surround ubiquitinated protein aggregates but are unable to form functional autophagosomes. vmp1 null cells also have additional defects in macropinocytosis and growth, which are not shared by other autophagy mutants. Remarkably, we show that these defects and also the aberrant PtdIns3P distribution are largely suppressed by the concomitant loss of Atg1, indicating that aberrant autophagic signaling on the ER inhibits macropinocytosis. These results suggest that Atg1 functions upstream of Vmp1 in this signaling pathway and demonstrates a previously unappreciated link between abnormal autophagy signaling and macropinocytosis. PMID- 25131298 TI - Lateral MoS2 p-n junction formed by chemical doping for use in high-performance optoelectronics. AB - This paper demonstrates a technique to form a lateral homogeneous 2D MoS2 p-n junction by partially stacking 2D h-BN as a mask to p-dope MoS2. The fabricated lateral MoS2 p-n junction with asymmetric electrodes of Pd and Cr/Au displayed a highly efficient photoresponse (maximum external quantum efficiency of ~7000%, specific detectivity of ~5 * 10(10) Jones, and light switching ratio of ~10(3)) and ideal rectifying behavior. The enhanced photoresponse and generation of open circuit voltage (VOC) and short-circuit current (ISC) were understood to originate from the formation of a p-n junction after chemical doping. Due to the high photoresponse at low VD and VG attributed to its built-in potential, our MoS2 p-n diode made progress toward the realization of low-power operating photodevices. Thus, this study suggests an effective way to form a lateral p-n junction by the h-BN hard masking technique and to improve the photoresponse of MoS2 by the chemical doping process. PMID- 25131299 TI - Variation in orgasm occurrence by sexual orientation in a sample of U.S. singles. AB - INTRODUCTION: Despite recent advances in understanding orgasm variation, little is known about ways in which sexual orientation is associated with men's and women's orgasm occurrence. AIM: To assess orgasm occurrence during sexual activity across sexual orientation categories. METHODS: Data were collected by Internet questionnaire from 6,151 men and women (ages 21-65+ years) as part of a nationally representative sample of single individuals in the United States. Analyses were restricted to a subsample of 2,850 singles (1,497 men, 1,353 women) who had experienced sexual activity in the past 12 months. MAIN OUTCOME MEASURES: Participants reported their sex/gender, self-identified sexual orientation (heterosexual, gay/lesbian, bisexual), and what percentage of the time they experience orgasm when having sex with a familiar partner. RESULTS: Mean occurrence rate for experiencing orgasm during sexual activity with a familiar partner was 62.9% among single women and 85.1% among single men, which was significantly different (F1,2848 = 370.6, P < 0.001, eta(2) = 0.12). For men, mean occurrence rate of orgasm did not vary by sexual orientation: heterosexual men 85.5%, gay men 84.7%, bisexual men 77.6% (F2,1494 = 2.67, P = 0.07, eta(2) = 0.004). For women, however, mean occurrence rate of orgasm varied significantly by sexual orientation: heterosexual women 61.6%, lesbian women 74.7%, bisexual women 58.0% (F2,1350 = 10.95, P < 0.001, eta(2) = 0.02). Lesbian women had a significantly higher probability of orgasm than did either heterosexual or bisexual women (P < 0.05). CONCLUSIONS: Findings from this large dataset of U.S. singles suggest that women, regardless of sexual orientation, have less predictable, more varied orgasm experiences than do men and that for women, but not men, the likelihood of orgasm varies with sexual orientation. These findings demonstrate the need for further investigations into the comparative sexual experiences and sexual health outcomes of sexual minorities. PMID- 25131300 TI - The glutamate receptor GluN2 subunit regulates synaptic trafficking of AMPA receptors in the neonatal mouse brain. AB - The N-methyl-D-aspartate receptor (NMDAR) plays various physiological and pathological roles in neural development, synaptic plasticity and neuronal cell death. It is composed of two GluN1 and two GluN2 subunits and, in the neonatal hippocampus, most synaptic NMDARs are GluN2B-containing receptors, which are gradually replaced with GluN2A-containing receptors during development. Here, we examined whether GluN2A could be substituted for GluN2B in neural development and functions by analysing knock-in (KI) mice in which GluN2B is replaced with GluN2A. The KI mutation was neonatally lethal, although GluN2A-containing receptors were transported to the postsynaptic membrane even without GluN2B and functional at synapses of acute hippocampal slices of postnatal day 0, indicating that GluN2A-containing NMDARs could not be substituted for GluN2B-containing NMDARs. Importantly, the synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluA1 was increased, and the transmembrane AMPAR regulatory protein, which is involved in AMPAR synaptic trafficking, was increased in KI mice. Although the regulation of AMPARs by GluN2B has been reported in cultured neurons, we showed here that AMPAR-mediated synaptic responses were increased in acute KI slices, suggesting differential roles of GluN2A and GluN2B in AMPAR expression and trafficking in vivo. Taken together, our results suggest that GluN2B is essential for the survival of animals, and that the GluN2B-GluN2A switching plays a critical role in synaptic integration of AMPARs through regulation of GluA1 in the whole animal. PMID- 25131302 TI - An antibody tag-team: driving neutralization through escape. AB - HIV rapidly mutates to escape antibody detection, and B cells counter this mutation by continual evolution to restore recognition, serendipitously resulting in the evolution of neutralizing activity in a fraction of infected individuals. A recent Cell paper describes how antibody repertoires stochastically collaborated, shaping the viral swarm and utilizing viral immune evasion to their advantage. PMID- 25131301 TI - The Dutch String-of-Pearls Stroke Study: protocol of a large prospective multicenter genetic cohort study. AB - BACKGROUND: In the last couple of years, genome-wide association studies have largely altered the scope in genetic research in diseases in which both environmental and genetic risk factors contribute to the disease. To date, the genetic risk loci identified in stroke have lagged behind those in other complex diseases, possibly because of the heterogeneity of stroke phenotypes. Sufficiently large cohorts with well-defined and detailed phenotyping of stroke patients are needed to identify additional genetic risk loci. DESIGN: The String of-Pearls Institute is a unique partnership between all eight University Medical Centers in the Netherlands. It was established in 2007 by the Netherlands Federation of University Medical Centers, and it conducts a large prospective cohort study in which comprehensive clinical data, detailed phenotyping of stroke, imaging data, and biomaterials are collected in a large cohort of stroke patients. AIMS: The study aims (1) to collect a sufficiently large prospective cohort of stroke patients, with well-defined phenotypes; (2) to collect blood samples and DNA in a standardized infrastructure, allowing for storing and analyzing the samples in a uniform way; (3) to investigate associations between genetic risk loci and stroke; (4) to create possibilities to perform epidemiological studies in a well-defined hospital-based cohort of stroke patients; and (5) to allow for pooling data with other large ongoing genetic stroke studies. PMID- 25131304 TI - MLL/KMT2A translocations in diffuse large B-cell lymphomas. AB - Translocations of the histone-lysine N-methyltransferase 2A (KMT2A) gene, formerly known as myeloid lymphoid leukemia/mixed-lineage leukemia gene, are commonly associated with high-risk de novo or therapy-associated B-cell and T cell lymphoblastic leukemias and myeloid neoplasms. Rare B-cell non-Hodgkin lymphomas harboring KMT2A translocations have been reported, but information regarding the clinical behavior of such cases is limited. Here, we describe two extranodal diffuse large B-cell lymphomas (DLBCLs): a primary thyroid DLBCL and a large cell transformation of a splenic marginal zone lymphoma, which displayed complex karyotypes and translocations involving chromosome 11q23 targeting the KMT2A gene. The pathological and clinical characteristics of these cases are discussed in the context of previously reported lymphomas associated with different types of KMT2A genetic aberrations. In contrast to the poor clinical outcomes of patients with acute leukemias and myeloid neoplasms associated with KMT2A translocations, patients with B-cell non-Hodgkin lymphomas, exhibiting similar translocations, appear to respond well to immunochemotherapy. Our findings add to the growing list of histone methyltransferase genes deregulated in DLBCL and highlight the diversity of mechanisms, altering the function of epigenetic modifier genes in lymphomas. PMID- 25131303 TI - Grocery store podcast about omega-3 fatty acids influences shopping behaviors: a pilot study. AB - OBJECTIVES: To determine whether listening to a podcast about omega-3 fatty acids (n-3s) while grocery shopping increased shoppers' awareness about and purchases of seafood and other foods rich in n-3s. METHODS: Repeated-measures design with a convenience sample (n = 56) of grocery shoppers who listened to the podcast while shopping. Pre- and postintervention semistructured interviews were conducted. The Theory of Reasoned Action was the study's framework. RESULTS: Shoppers were primarily females (mean age, 41 +/- 15.3 years). Their perceived ability to buy [t(55) = 6.27, P < .0001] and perceived importance regarding buying [t(55) = 3.38, P < .01] n-3-rich foods improved significantly. At least 1 n-3 rich food (mean, 1.5 +/- 0.8) was purchased by 30%, and 79% planned future purchases. CONCLUSION AND IMPLICATIONS: Podcasts may effectively communicate nutrition information. More research with a larger sample size is needed to evaluate the effects of the podcast on long-term changes in shopping behavior. PMID- 25131305 TI - Role of turmeric in oxidative modulation in end-stage renal disease patients. AB - Oxidative stress is considered as a major player in uremia-associated morbidity and mortality in hemodialysis (HD) patients. The aim of this study was to evaluate the effects of turmeric on oxidative stress markers in HD patients. This study was a prospective and double-blind randomized clinical trial. Fifty HD patients aged 18-60 years were recruited after fulfilling the inclusion criteria. Patients were randomly categorized into 2 groups: trial group received turmeric and control group received placebo for 8 weeks. Each patient in the trial group received turmeric, whereas the control group received starch for the same 8 weeks. Plasma malondialdehyde (MDA), red blood cell (RBC) antioxidant enzyme activities as glutathione peroxidase (GPX), glutathione reductase (GR), and catalase (CAT), cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglyceride, albumin, and hemoglobin were also measured before and after study. Although MDA level was reduced in both groups, the ratio of decrease was significantly higher in the turmeric group (0.2 vs. 0.1, P = 0.040). Three enzymes of GPX, GR, and CAT levels were increased in both groups; the ratio of increased was significantly higher in the turmeric group for the CAT enzyme (0.73 vs. 0.54; P = 0.02). Also, significant elevation of albumin level in the turmeric group compared with the control group was observed (P = 0.001). Regular ingestion of turmeric reduces plasma MDA and increases RBC CAT activity and plasma albumin levels in HD patients. Turmeric showed no adverse effects. PMID- 25131306 TI - The expression and localization of Crb3 in developmental stages of the mice embryos and in different organs of 1-week-old female mice. AB - Crumbs homolog 3 (Crb3) is a member of the Crumbs family of proteins. This protein may play a role in epithelial cell polarity and is associated with tight junctions at the apical surface of epithelial cells. Alternative transcriptional splice variants that encode different Crb3 isoforms have been characterized. The expression of Crb3 mRNA and protein was observed in the pre-implantation mouse embryos and different organs of 1-week-old mouse, and Crb3 expression was primarily observed in the cytoplasm. Crb3 was expressed in a unique temporal pattern in pre-implantation embryos. The main characteristic of Crb3 expression was that the positive signals were stronger in the mature oocytes and zygotes than in the 2-cell, 4-cell, and 8-cell stages and the morula, but a similar level of high expression was observed in blastocysts. Therefore, the Crb3 expression signal during the course of development process grew gradually stronger from the 2-cell stage to blastocyst. In addition, Crb3 protein was widely distributed in each stage of the post-implantation embryos. Crb3 expression was observed in the inner cell mass, trophoblast cells and endoderm of E4.5d embryos; in the chorion, amnion, trophoblast cells, yolk sac endoderm and embryo ectoderm of E7.5d embryos; in the amnion and limb bud of E8.0d embryos; and in the semicircular canal epithelium, retina, lens vesicle and liver tissue of E13.5d embryos. Crb3 was expressed at different levels in different organs of 1-week-old mouse with the strengths in the following order: kidney > small intestine > stomach > uterus > liver > skeletal muscle > cerebellum > brain. The presence of Crb3 in many organs and the regularity of Crb3 distribution in the process of mouse embryonic development indicate that Crb3 protein plays an important role in establishing and maintaining the polarity of mouse embryos. PMID- 25131307 TI - Reversible nano-structuring of SrCrO3-delta through oxidation and reduction at low temperature. AB - Oxygen vacancies are often present in complex oxides as point defects, and their effect on the electronic properties is typically uniform and isotropic. Exploiting oxygen deficiency in order to generate controllably novel structures and functional properties remains a challenging goal. Here we show that epitaxial strontium chromite films can be transformed, reversibly and at low temperature, from rhombohedral, semiconducting SrCrO(2.8) to cubic, metallic perovskite SrCrO(3-delta). Oxygen vacancies in SrCrO(2.8) aggregate and give rise to ordered arrays of {111}-oriented SrO(2) planes interleaved between layers of tetrahedrally coordinated Cr(4+) and separated by ~1 nm. First-principle calculations provide insight into the origin of the stability of such nanostructures and, consistent with the experimental data, predict that the barrier for O(2-) diffusion along these quasi-two-dimensional nanostructures is significantly lower than that in cubic SrCrO(3-delta). This property is of considerable relevance to solid oxide fuel cells in which fast O(2-) diffusion reduces the required operating temperature. PMID- 25131308 TI - Ursolic acid triggers nonprogrammed death (necrosis) in human glioblastoma multiforme DBTRG-05MG cells through MPT pore opening and ATP decline. AB - SCOPE: Ursolic acid, a natural pentacyclic triterpenic acid, possesses anticancer potential and diverse biological effects, but its correlation with glioblastoma multiforme cells and different modes of cell death is unclear. We studied the cellular actions of human glioblastoma multiforme DBTRG-05MG cells after ursolic acid treatment and explored cell-selective killing effect of necrotic death as a cell fate. METHODS AND RESULTS: Ursolic acid effectively reversed temozolomide resistance and reduced DBTRG-05MG cell viability. Surprisingly, ursolic acid failed to stimulate the apoptosis- and autophagy-related signaling networks. The necrotic death was characterized by annexin V/propidium iodide double-positive detection and release of high-mobility group protein B1 and lactate dehydrogenase. These ursolic acid elicited responses were accompanied by reactive oxygen species generation and glutathione depletion. Rapid mitochondrial dysfunction was paralleled by the preferential induction of necrosis, rather than apoptotic death. Mitochondrial permeability transition (MPT) is a phenomenon to provide the onset of mitochondrial depolarization during cellular necrosis. The opening of MPT pores that were mechanistically regulated by cyclophilin D, and adenosine triphosphate decline occurred in treated necrotic DBTRG-05MG cells. Cyclosporine A (an MPT pore inhibitor) prevented ursolic acid-provoked necrotic death and the acid-involved key regulators. CONCLUSION: Our study is the first to report that ursolic acid-modified mitochondrial function triggers defective death by necrosis in DBTRG-05MG cells rather than augmenting programmed death. PMID- 25131309 TI - In Vivo Evaluation of Chemical Composition of Eight Types of Urinary Calculi Using Spiral Computerized Tomography in a Chinese Population. AB - BACKGROUND: This study was conducted to evaluate the chemical composition of eight types of urinary calculi using spiral computerized tomography (CT) in vivo. METHODS: From October 2011 to February 2013, upper urinary tract calculi were obtained from 122 patients in the department of urinary surgery of the First Affiliated Hospital of Soochow University. All patients were scanned with a 64 detector row helical CT scanner using 6.50 mm collimation before ureterorenoscopy. Data from the preoperative spiral CT scans and postoperative chemical composition of urinary calculi were collected. RESULTS: The chemical composition analysis indicates that there were five types of pure calculi and three types of mixed calculi, including 39 calcium oxalate calculi, 12 calcium phosphate calculi, 10 calcium carbonate calculi, 8 magnesium ammonium phosphate calculi, 6 carbonated apatite, 21 uric acid/ammonium urate calculi, 10 uric acid/calcium oxalate calculi, and 16 calcium oxalate/calcium phosphate calculi. There were significant differences in the mean CT values among the five types of pure calculi (P < 0.001). Furthermore, we also observed significant differences in the mean CT values among three types of mixed calculi (P < 0.001). Significant differences in the mean CT values were also found among eight types of urinary calculi (P < 0.001). However, no statistically significant difference was observed between the mean CT values of magnesium ammonium phosphate calculi and uric acid/calcium oxalate calculi (P = 0.262). CONCLUSION: Our findings suggest that spiral CT could be a promising tool for determining the chemical composition of upper urinary tract calculi. PMID- 25131311 TI - History of the Harvard ChemDraw project. PMID- 25131310 TI - The effect of immunoadsorption with the Immusorba TR-350 column on coagulation compared to plasma exchange. AB - BACKGROUND AND OBJECTIVES: Plasma exchange (PE) and immunoadsorption with the Immusorba TR-350 column (IA) are used to remove autoantibodies from plasma in acute neurological autoimmune disorders. The impact of IA on coagulation and on low molecular weight heparin (LMWH) levels in comparison with PE was investigated. PATIENTS AND METHODS: In five patients with neurological autoimmune disorders, coagulation parameters (global tests, coagulation factors) were measured before and after PE or IA (Part A). In five other patients under anticoagulation with LMWH, anti-Xa activity and global tests were measured before and after the treatments (Part B). RESULTS: After PE, coagulation factors were significantly reduced by 50-70%. After IA, a distinct reduction was observed for fibrinogen, but not for antithrombin and most of the other coagulation factors. Anti-Xa activity was reduced after PE (from 0.57 +/- 0.10 to 0.13 +/- 0.05 IU/ml) and almost unchanged after IA. CONCLUSION: It is advisable to discontinue or to reduce LMWH doses and to monitor coagulation parameters and anti-Xa activity after PE or IA to decide about further LMWH dosing. PMID- 25131312 TI - Vitamin D and the athlete: emerging insights. AB - Interest in Vitamin D has risen considerably recently with many athletes now advised to take daily vitamin D supplements. The reason for this interest is partly not only attributed to the resurgence of the Vitamin D-deficient disease rickets but also due to the discovery of a Vitamin D receptor in many tissues suggesting a more global role for Vitamin D than previously considered. Unlike the other vitamins that are obtained through the diet, Vitamin D is unique since endogenous synthesis following ultraviolet B (UVB) exposure is the predominant route of entry into systemic circulation. Moreover, Vitamin D could be better classed as a seco-steroid, given that its structure is similar to that of a steroid, and its production is derived from a cholesterol precursor (7 dehydrocholesteol) in the skin. The classification of Vitamin D status is currently subject to considerable debate with many authors opposing governing body recommendations. Regardless of the suggested optimal concentration, there is now growing evidence to suggest that many athletes are in fact Vitamin D deficient, especially in the winter months largely as a consequence of inadequate sun exposure, combined with poor dietary practices, although the consequences of such deficiencies are still unclear in athletic populations. Impaired muscle function and reduced regenerative capacity, impaired immune function, poor bone health and even impaired cardiovascular function have all been associated with low Vitamin D in athletes, however, to date, the majority of studies on Vitamin D have described associations and much more research is now needed examining causation. PMID- 25131313 TI - Morphological characteristics of the cranial root of the accessory nerve. AB - There has been the controversy surrounding the cranial root (CR) of the accessory nerve. This study was performed to clarify the morphological characteristics of the CR in the cranial cavity. Fifty sides of 25 adult cadaver heads were used. The accessory nerve was easily distinguished from the vagus nerve by the dura mater in the jugular foramen in 80% of 50 specimens. The trunk of the accessory nerve from the spinal cord penetrated the dura mater at various distances before entering the jugular foramen. In 20% of the specimens there was no dural boundary. In these cases, the uppermost cranial rootlet of the accessory nerve could be identified by removing the dura mater around the jugular foramen where it joined to the trunk of the accessory nerve at the superior vagal ganglion. The cranial rootlet was formed by union of two to four short filaments emerging from the medulla oblongata (66%) and emerged single, without filament (34%), and usually joined the trunk of the accessory nerve directly before the jugular foramen. The mean number of rootlets of the CR was 4.9 (range 2-9) above the cervicomedullary junction. The CR of the accessory nerve was composed of two to nine rootlets, which were formed by the union of two to four short filaments and joined the spinal root of the accessory nerve. The CR is morphologically distinct from the vagus nerve, confirming its existence. PMID- 25131314 TI - Observation is a valid way of assessing common variables in typical babbling and identifies infants who need further support. AB - AIM: It is important to identify speech and language difficulties in children as early as possible. This study investigated the validity of observing babbling structure and consonant articulation. METHODS: We focused on the language capabilities of children, with and without cleft palates, at 12 months of age (n = 29) and 18 months of age (n = 38), comparing observations made by speech and language pathologists on babbling structure and consonant articulation to audio recordings phonetically transcribed by experts blinded to the aim of the study. Descriptive cross-tabs, sensitivity, specificity and predictive values were analysed to investigate the validity of agreement between the methods. RESULTS: We found high mean agreement between the two methods (94%) and within the observation (100%) and transcription (88.5%) teams when it came to canonical babbling, high-pressure/oral stop consonants and anterior placement of bilabial and dental/alveolar consonants. The observations had high specificity and negative predictive values (0.90-1) at both ages, with low to moderate sensitivity (0-0.86). However, there was low agreement, between and within the groups, on the number of consonant types and the unproven predictive variable glottal place of articulation. CONCLUSION: Previously suggested predictive measures of babbling were shown to be valid and observation is a reliable method of identifying children who need further support. PMID- 25131315 TI - Endogenous concentrations, pharmacokinetics, and selected pharmacodynamic effects of a single dose of exogenous GABA in horses. AB - The anti-anxiety and calming effects following activation of the GABA receptor have been exploited in performance horses by administering products containing GABA. The primary goal of the study reported here was to describe endogenous concentrations of GABA in horses and the pharmacokinetics, selected pharmacodynamic effects, and CSF concentrations following administration of a GABA-containing product. The mean (+/-SD) endogenous GABA level was 36.4 +/- 12.5 ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral dose of GABA (1650 mg). Blood, urine, and cerebrospinal fluid (n = 2) samples were collected at time 0 and at various times for up to 48 h and analyzed using LC-MS. Plasma clearance and volume of distribution was 155.6 and 147.6 L/h and 0.154 and 7.39 L for the central and peripheral compartments, respectively. Terminal elimination half-life was 22.1 (intravenous) and 25.1 (oral) min. Oral bioavailability was 9.81%. Urine GABA concentrations peaked rapidly returning to baseline levels by 3 h. Horses appeared behaviorally unaffected following oral administration, while sedative-like changes following intravenous administration were transient. Heart rate was increased for 1 h postintravenous administration, and gastrointestinal sounds decreased for approximately 30 min following both intravenous and oral administration. Based on a limited number of horses and time points, exogenously administered GABA does not appear to enter the CSF to an appreciable extent. PMID- 25131316 TI - From yeast to patient neurons and back again: powerful new discovery platform. AB - No disease-modifying therapies are available for synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple systems atrophy (MSA). The lack of therapies has been impeded by a paucity of validated drug targets and problematic cell-based model systems. New approaches are therefore needed to identify genes and compounds that directly target the underlying cellular pathologies elicited by the pathological protein, alpha synuclein (alpha-syn). This small, lipid-binding protein impinges on evolutionarily conserved processes such as vesicle trafficking and mitochondrial function. For decades, the genetically tractable, single-cell eukaryote, budding yeast, has been used to study nearly all aspects of cell biology. More recently, yeast has revealed key insights into the underlying cellular pathologies caused by alpha-syn. The robust cellular toxicity caused by alpha-syn expression facilitates unbiased high-throughput small-molecule screening. Critically, one must validate the discoveries made in yeast in disease-relevant neuronal models. Here, we describe two recent reports that together establish yeast-to-human discovery platforms for synucleinopathies. In this exemplar, genes and small molecules identified in yeast were validated in patient-derived neurons that present the same cellular phenotypes initially discovered in yeast. On validation, we returned to yeast, where unparalleled genetic approaches facilitated the elucidation of a small molecule's mode of action. This approach enabled the identification and neuronal validation of a previously unknown "druggable" node that interfaces with the underlying, precipitating pathologies caused by alpha-syn. Such platforms can provide sorely needed leads and fresh ideas for disease-modifying therapy for these devastating diseases. PMID- 25131317 TI - [Hepatitis due to secondary syphilis]. PMID- 25131319 TI - Communication satisfaction of professional nurses working in public hospitals. AB - AIM: This study aimed to establish and describe the level of communication satisfaction that professional nurses experience in selected public hospitals in the City of Johannesburg, South Africa. BACKGROUND: The success of any organisation depends on the effectiveness of its communication systems and the interaction between staff members. METHOD: Data were collected by means of questionnaires, based on the Communication Satisfaction Questionnaire (CSQ), from a sample of 265 professional nurses from different categories, chosen using a disproportionate random stratified sampling method. RESULTS: The results indicated poor personal feedback between nurse managers (operational managers) and professional nurses, as well as dissatisfaction among nurse managers and professional nurses with regard to informal communication channels. A lack of information pertaining to policies, change, financial standing and achievements of hospitals was identified. CONCLUSION: Nurse managers should play a leadership role in bringing staff of different departments together by creating interactive communication forums for the sharing of ideas. IMPLICATIONS FOR NURSING MANAGEMENT: The results emphasise the need for nurse managers to improve communication satisfaction at all levels of the hospital services in order to enhance staff satisfaction and create a positive working environment for staff members. PMID- 25131318 TI - Bouveret's syndrome. PMID- 25131320 TI - Increased prevalence of autoimmune diseases in functional gastrointestinal disorders: case-control study of 23471 primary care patients. AB - BACKGROUND: There is increasing evidence that impaired mucosal defence mechanisms are implicated in the pathogenesis of the functional gastrointestinal disorders (FGIDs), allowing inappropriate immune activation. AIM: To test the hypothesis that an excess of autoimmune disorders among sufferers, using a large primary care database to examine this. METHODS: Cases were diagnosed with FGIDs - irritable bowel syndrome (IBS), functional dyspepsia (FD), chronic idiopathic constipation (CIC), and multiple FGIDs. Controls were those without FGIDs. Prevalence of autoimmune disorders was compared between cases and controls using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 23,471 patients (mean age 51.4 years, 66.1% female). Prevalence of autoimmune disorders was greater among all FGIDs, compared with controls without. In those with FD (OR 1.35; 95% CI 1.12-1.63), CIC (OR 1.75; 95% CI 1.11-2.75), or multiple FGIDs (OR 1.49; 95% CI 1.25-1.77) this was statistically significant after controlling for age and gender. Rheumatological autoimmune disorders were significantly more frequent in those with FD (OR 1.44; 95% CI 1.15-1.80), CIC (OR 1.84; 95% CI 1.08 3.13), or multiple FGIDs (OR 1.53; 95% CI 1.24-1.88), after controlling for age and gender. However, endocrine autoimmune disorders were no more frequent in those with FGIDs, after controlling for age and gender. CONCLUSIONS: In a large sample of primary care patients, there was a significantly higher prevalence of autoimmune disorders among those with FD, CIC, or multiple FGIDs not explained by differences in age or gender. We were unable to control for concomitant drug use, which may partly explain this association. PMID- 25131321 TI - Timing of and outcomes after selective termination of anomalous fetuses in dichorionic twin pregnancies. AB - OBJECTIVE: The objective of this article is to determine if selective termination (ST) of an anomalous dichorionic twin at early gestational age (GA) is associated with a decreased risk of fetal loss and prematurity. METHOD: All patients who had ST for dichorionic twin pregnancies from 2004 through 2010 at Mount Sinai Medical Center were included. Data were collected via chart review and patient interview. Two case-control analyses were carried out: first, cases were nonviable deliveries, and controls were live births; and second, cases were live births <37 weeks' GA, and controls were live births >=37 weeks' GA. Univariable and then multivariable analyses identified characteristics associated with pregnancy loss and prematurity. RESULTS: Among 80 participants, there were four (5%) fetal losses and 15 (19%) premature births. GA at ST was the only characteristic associated with pregnancy loss in multivariable exact logistic regression [OR = 1.43, 95% CI (1.03, 2.26), P = 0.03]. GA at ST was the only characteristic associated with premature delivery in multivariable exact logistic regression [OR = 1.18, 95% CI (1.02, 1.37), P = 0.03]. CONCLUSION: This study suggests that ST performed earlier in pregnancy is associated with decreased fetal loss and prematurity. PMID- 25131322 TI - Laparoscopic gastrectomy after coronary artery bypass grafting using the right gastroepiploic artery: a report of two cases. AB - We successfully executed laparoscopic distal gastrectomy in two patients who had previously undergone coronary artery bypass grafting using the right gastroepiploic artery (RGEA). A laparoscopic distal gastrectomy preserving the RGEA graft with Roux-en-Y reconstruction was performed on two men, one 69 years of age and one 73 years of age. In both cases, the RGEA was used during coronary artery bypass grafting for the posterior descending branch. The laparoscopic approach helped avoid injury to the RGEA associated with laparotomy and retractor placement. In addition, the locations of ports necessary for laparoscopy were situated away from the RGEA graft and from adhesions resulting from bypass. Using typical laparoscopic settings, we were able to easily identify the grafted RGEA. Thus, laparoscopic distal gastrectomy is not only less invasive than open gastrectomy procedures, but it is also associated with a lower risk of injury to the RGEA graft. PMID- 25131323 TI - Transcervical approach to percutaneous endoscopic gastrostomy tube insertion in a patient with head and neck cancer. AB - This is the case of a 48-year-old woman with recurrent head and neck cancer. Six years before presenting at our institution, she was diagnosed with a moderately differentiated squamous cell carcinoma involving the right maxilla and underwent surgical resection followed by chemoradiation. More recently, she presented at our institution with oral bleeding and pain. Examination revealed severe trismus, and biopsy demonstrated recurrent squamous cell carcinoma. She underwent surgical resection with a plan for simultaneous placement of a feeding gastrostomy tube. Owing to the near non-existent mouth opening, traditional per-oral placement of a percutaneous endoscopic gastrostomy (PEG) tube was impossible. Intraoperatively, following tumor resection, endoscopy was performed via direct pharyngeal access through a right cervical incision. The PEG tube was then placed uneventfully. Numerous studies have shown the superiority of PEG tubes over either radiologically or surgically placed gastrostomy tubes. This report describes an approach to PEG placement in a patient in whom per-oral placement was not feasible. PMID- 25131324 TI - Laparoscopic reduced port surgery for schwannoma of the sigmoid colon: a case report. AB - A 74-year-old woman who developed schwannoma of the sigmoid colon was referred to our hospital for colonography to determine the cause of her stool occult blood. Colonoscopy revealed a submucosal tumor, which measured 3 cm in diameter, in the sigmoid colon. Endoscopic ultrasonography revealed a low echoic, homogeneous and demarcated submucosal tumor that continued into the fourth layer of the colonic wall. Gastrointestinal stromal, myogenic or neurogenic tumor was suspected, and thus, laparoscopic sigmoidectomy was carried out. We used two ports during the operation, a SILS Port in the umbilical region and a 12-mm port in the right lower abdominal wall, and performed sigmoidectomy with D2 lymph node dissection. Histological findings revealed spindle-like tumor cells with multiform nuclei. The tumor was diagnosed by immunostaining as benign schwannoma of the sigmoid colon. The conventional surgical treatment for schwannoma of the digestive tract is partial resection, but if preoperative diagnosis is unknown, radical resection with lymphadenectomy is acceptable for submucosal tumors in the digestive tract. In this case, laparoscopic reduced port surgery using only one or two ports may be more feasible and beneficial with regard to cosmesis and reduced postoperative pain than conventional laparoscopic colectomy. PMID- 25131325 TI - Sterile abdominal abscess resulting from remnant laparoscopic clips after sigmoidectomy: a case report and literature review. AB - The occurrence of intra-abdominal sterile abscesses due to remnant clips after laparoscopic sigmoidectomy is rare. Here, we report one such case in a 74-year old woman. Two years after laparoscopic sigmoidectomy, abdominal CT indicated an area of fluid accumulation approximately 5 cm in diameter and located in the middle of the abdominal cavity that contained a cluster of clips. Fine-needle aspiration of the fluid was performed through the wall of the sigmoid colon. The luminal fluid was found not to contain cancer cells on histological examination. After 1 year, abdominal surgery was performed. The abscess was located in the mesorectum at the anastomosis site; it was incised and a significant quantity of ivory-white viscous solution containing a cluster of clips was extracted. This case emphasizes the importance of reducing the number of clips used in laparoscopic surgery. PMID- 25131326 TI - Laparoscopic resection of hepatoblastoma: report of a case. AB - Despite the increasing number of recent reports on laparoscopic resection of malignant liver tumors in adults, there have been few reports involving children. In this paper we discuss the laparoscopic resection of a hepatoblastoma in a 1 year-old boy. The CT scan revealed an exophytic hepatic tumor on S5 measuring 6 * 5 * 4 cm after preoperative chemotherapy. The operation time was 225 min with an estimated blood loss of about 38 mL; intraoperative transfusion was not required. Radiofrequency-assisted precoagulation was performed. The patient had an uncomplicated recovery and started postoperative chemotherapy on postoperative day 12. Our literature search revealed only five reported cases of laparoscopic resection of hepatoblastoma in which there was no postoperative complication or recurrence. Laparoscopic resection of a hepatoblastoma in a selected subgroup of patients can be safe and feasible. PMID- 25131327 TI - Laparoscopy assisted middle-segment-preserving pancreatectomy for multiple pancreatic neuroendocrine tumors: report of a case. AB - For multiple low-grade malignant tumors located in the pancreatic head and tail, middle-segment-preserving pancreatectomy (MSPP) is sometimes indicated. However, MSPP has rarely been performed laparoscopically. Here we report the first case of laparoscopic MSPP for multiple pancreatic neuroendocrine tumors diagnosed preoperatively under an endoscopic ultrasound-guided fine-needle aspiration biopsy. A 70-year-old man had multiple small tumors located in the pancreatic head, body and tail. Endoscopic ultrasound-guided fine-needle aspiration biopsy with immunohistochemical staining made a definitive diagnosis of a pancreatic neuroendocrine tumor (G1). To preserve the 5-cm pancreas body, we successfully performed laparoscopic MSPP: subtotal stomach-preserving pancreaticoduodenectomy followed by distal pancreatosplenectomy. Pathological examination revealed negative surgical margin after resection. Postoperative course was uneventful, and at 14 months after the operation, the patient remains tumor-free. The patient has discontinued insulin supplement therapy but does use an oral hypoglycemic agent. Laparoscopy-assisted MSPP, with reconstruction through a 6-cm transverse incision, can be safely performed for selected cases of borderline and malignant lesions. PMID- 25131328 TI - Hand-assisted laparoscopic splenectomy for sclerosing angiomatoid nodular transformation of the spleen complicated by chronic disseminated intravascular coagulation: a case report. AB - A 36-year-old man who presented with a nosebleed and anemia was referred to our hospital. Laboratory test results showed platelet depletion, decreased levels of fibrinogen, and increased fibrinogen degeneration products. CT showed a 13-cm splenic tumor. T2 -weighted MRI revealed a high-intensity mass. We preoperatively diagnosed splenic hemangioma with chronic disseminated intravascular coagulation and scheduled an operation to relieve the disseminated intravascular coagulation. We also performed hand-assisted laparoscopic splenectomy to ensure easy handling of the splenomegaly. The resected specimen microscopically consisted of hemorrhages and hemangiomatous lesions, and multiple angiomatoid nodules were scattered and separated by fibrocollagenous stroma with inflammatory cells. Three types of vessels (capillaries, sinusoids and small veins) were contained in the angiomatoid nodules, and the pathological diagnosis was sclerosing angiomatoid nodular transformation. The results of this case suggest that we should consider sclerosing angiomatoid nodular transformation in the differential diagnosis of patients with splenic tumors, as sclerosing angiomatoid nodular transformation with hemangiomatous features may cause coagulation disorders for which splenectomy should be performed. PMID- 25131329 TI - Laparoscopic repair of Bochdalek hernia with intrathoracic kidney in a 2-year-old child. AB - Intrathoracic kidney with Bochdalek hernia is a very rare congenital anomaly. Some case reports have discussed repair by laparotomy or thoracotomy. We report a case in a child performed using a laparoscopic approach. A 2-year-old boy arrived at our hospital with gastric volvulus caused by a left-sided Bochdalek hernia. CT also showed a left-sided intrathoracic kidney. After conservative therapy for the volvulus, laparoscopic repair of the diaphragmatic hernia was performed. The key problem during the operation was the presence of the intrathoracic kidney. If direct closure of the hernia had been performed without the intrathoracic kidney having been relocated to the abdomen, a complete closure would have been impossible because of the renal vessels. After the intrathoracic kidney was relocated to the abdomen, the diaphragmatic defect was closed. The boy has been doing well without complications for 5 years, and CT reveals that the left-sided kidney is almost normally positioned. PMID- 25131330 TI - Hybrid technique for laparoscopic incisional ventral hernia repair combining laparoscopic primary closure and mesh repair. AB - INTRODUCTION: Incisional ventral hernia is one of the most common surgical complications after laparotomy. Laparoscopic repair of incisional ventral hernia has been conducted recently, and the advantages of this procedure have been reported. However, in large orifice cases, the recurrence rate is increased. To improve recurrence rates in large cases, a hybrid method combining laparoscopic primary closure and mesh repair can be applied. MATERIALS AND SURGICAL TECHNIQUE: Monofilament thread was inserted into the abdominal cavity for hernia closure and pulled from the other side of the orifice. The same procedure was performed from the upper side to the lower side without closure, and all thread was placed in line. Both sides of the thread were then introduced to the midline of the incision through a subcutaneous route. This procedure was conducted with an introducer. All threads were tied, and then a mesh was placed. DISCUSSION: Hybrid techniques already combine mini-laparotomy for hernia closure and subsequent laparoscopic intraoperative onlay mesh for reinforcement, but such techniques require laparotomy. In our technique, closure of the linea alba does not require laparotomy. All procedures were performed laparoscopically. This procedure is very easy and safe, and does not require the abdominal cavity to be opened. Thus, hybrid methods are effective for treating cases of incisional hernia involving a large orifice. PMID- 25131331 TI - The role of IgG4 (+) plasma cells in the association of Hashimoto's thyroiditis with papillary carcinoma. AB - Hashimoto's thyroiditis (HT) is considered to be a risk factor for the formation of papillary carcinoma. The association of IgG4-related sclerosing disease with tumor is reported to be as sporadic cases in many organs. In this study, it was intended to re-classify the HT diagnosed cases on the basis of the existence of IgG4 (+) plasma cells; to investigate the clinicopathologic and histopathologic features of the both groups; and in addition, to evaluate the papillary carcinoma prevalence in IgG4 (+) and IgG4 (-) HT cases as well as the prognostic parameters between these groups. Totally 59 cases between the years 2008-2013, 29 of which contain Hashimoto thyroiditis diagnosis in total thyroidectomy materials, and 30 of which contain the diagnosis of HT+papillary carcinoma, were included in the study. The materials were immunohistochemically applied IgG and IgG4; and the cases were classified in two groups as IgG4-positive HT and IgG4-negative HT containing cases, on the basis of IgG4/IgG rate. All histopathologic and clinicopathologic parameters between these two groups, as well as their association with papillary carcinoma were investigated. Thirty eight (64.4%) of total 59 cases were NonIgG4 thyroiditis, and 21 (35.5%) were IgG4 thyroiditis. Tumors were detected in 14 (36.8%) of the NonIgG4 thyroiditis cases, and in 16 (76.1%) of the IgG4 thyroiditis cases. The association of IgG4 thyroiditis with tumor is statistically significant (p < 0.004). Multifocality was found to be at a higher rate in IgG4 thyroiditis cases. Perithyroidal extension was detected in six of the cases with tumor, and five of the six cases were IgG4 thyroiditis cases. The association of IgG4 (+) HT cases with increased papillary carcinoma prevalence is suggestive of that IgG4 (+) plasma cells can play a role in carcinogenesis in papillary carcinomas developed in HTs, without a chronic sclerosing ground. In addition, although the number of cases is limited, the high association of IgG4 (+) plasma cells with adverse prognostic parameters such as multifocality and extrathyroidal extension is attention-grabbing. To render these possibilities evaluable, studies to be carried out with larger case series are needed. PMID- 25131332 TI - IFITM3-containing exosome as a novel mediator for anti-viral response in dengue virus infection. AB - Interferon-inducible transmembrane proteins 1, 2 and 3 (IFITM1, IFITM2 and IFITM3) have recently been identified as potent antiviral effectors that function to suppress the entry of a broad range of enveloped viruses and modulate cellular tropism independent of viral receptor expression. However, the antiviral effect and mechanisms of IFITMs in response to viral infections remain incompletely understood and characterized. In this work, we focused our investigation on the function of the extracellular IFITM3 protein. In cell models of DENV-2 infection, we found that IFITM3 contributed to both the baseline and interferon-induced inhibition of DENV entry. Most importantly, our study for the first time demonstrated the presence of IFITM-containing exosome in the extracellular environment, and identified an ability of cellular exosome to intercellularly deliver IFITM3 and thus transmit its antiviral effect from infected to non infected cells. Thus, our findings provide new insights in the basic mechanisms underlying the actions of IFITM3, which might lead to future development of exosome-mediated anti-viral strategies using IFITM3 as a therapeutic agent. Conceivably, variations in the basal and inducible levels of IFITMs, as well as in intracellular and extracellular levels of IFITMs, might predict the severity of dengue virus infections among individuals or across species. PMID- 25131333 TI - Dietary squid ink polysaccharides ameliorated the intestinal microflora dysfunction in mice undergoing chemotherapy. AB - Gastrointestinal mucositis and infection by chemotherapy treatment are associated with alteration of intestinal microflora and bacterial translocation due to the potential damage induced by anti-cancer drugs on the intestinal barrier and microbiota homeostasis. This study aimed to investigate the protective effect of dietary polysaccharides on chemotherapy induced intestinal microflora dysfunction. In the current contribution, with a mouse model intraperitoneally injected with 50 mg kg(-1) of cyclophosphamide (Cy) for 2 days, we revealed that polysaccharides from the ink of Ommastrephes bartrami (OBP) altered the intestinal microflora composition. OBP retarded the excessive growth of intestinal bacteria induced by cyclophosphamide, based on 16S rRNA gene (16S rDNA) quantification. The clone libraries of intestinal bacteria 16S rDNA were used to decipher the difference in bacterial community structures in different groups of mice. Followed by RFLP evaluation and OTU abundance analysis, they imply that OBP changed the intestinal microflora composition, in which the quantity of probiotic Bifidobacterium got up-regulated but Bacteroidetes decreased in mice undergoing chemotherapy. Our results may have important implications for OBP as a functional food component or nutrient against chemotherapy induced intestinal injury and potential pathogenic intestinal disorders involving inflammation and infection. PMID- 25131334 TI - Chimeric RNAs generated by intergenic splicing in normal and cancer cells. AB - A hallmark of many neoplasias is chromosomal rearrangement, an event that commonly results in the fusion of two separate genes. The RNA and protein resulting from these gene fusions often play critical roles in cancer development, maintenance, and progression. Traditionally, these fusion products are thought to be produced solely due to DNA level changes and are therefore considered unique to cancer. Recent advances in microarray and deep-sequencing have revealed many more fusion transcripts. Surprisingly, some are without detectable rearrangement at the DNA level. Reports have demonstrated that at least some of these chimeric RNAs are generated via intergenic splicing. In this review, we highlight three examples of these noncanonical chimeric transcripts that are formed by trans-splicing or cis-splicing of adjacent genes and summarize the knowledge we have regarding these noncanonical fusions. We discuss the implications of the chimeric RNAs in both cancer and normal physiology, as some of these fusion transcripts are found in normal, noncancerous cells with sequences identical to those generated by canonical chromosomal translocation found in cancer cells. Finally, we present methods that are currently being used to discover additional chimeric RNAs. PMID- 25131335 TI - Higher biodiversity is required to sustain multiple ecosystem processes across temperature regimes. AB - Biodiversity loss is occurring rapidly worldwide, yet it is uncertain whether few or many species are required to sustain ecosystem functioning in the face of environmental change. The importance of biodiversity might be enhanced when multiple ecosystem processes (termed multifunctionality) and environmental contexts are considered, yet no studies have quantified this explicitly to date. We measured five key processes and their combined multifunctionality at three temperatures (5, 10 and 15 degrees C) in freshwater aquaria containing different animal assemblages (1-4 benthic macroinvertebrate species). For single processes, biodiversity effects were weak and were best predicted by additive-based models, i.e. polyculture performances represented the sum of their monoculture parts. There were, however, significant effects of biodiversity on multifunctionality at the low and the high (but not the intermediate) temperature. Variation in the contribution of species to processes across temperatures meant that greater biodiversity was required to sustain multifunctionality across different temperatures than was the case for single processes. This suggests that previous studies might have underestimated the importance of biodiversity in sustaining ecosystem functioning in a changing environment. PMID- 25131336 TI - Successful treatment of non-invasive bladder tumour in a haemophilia A patient with high-responding inhibitors: a case report. PMID- 25131338 TI - Prescribing patterns and adherence to medication among South-Asian, Chinese and white people with type 2 diabetes mellitus: a population-based cohort study. AB - AIM: To determine the prescribing of and adherence to oral hypoglycaemic agents, insulin, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and statin therapy among South-Asian, Chinese and white people with newly diagnosed diabetes. METHODS: The present study was a population-based cohort study using administrative and pharmacy databases to include all South-Asian, Chinese and white people aged >= 35 years with diabetes living in British Columbia, Canada (1997-2006). Adherence to each class of medication was measured using proportion of days covered over 1 year with optimum adherence defined as >= 80%. RESULTS: The study population included 9529 South-Asian, 14 084 Chinese and 143 630 white people with diabetes. The proportion of people who were prescribed angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statin or oral hypoglycaemic agents was <= 50% for all groups. South-Asian and Chinese people had significantly lower adherence for all medications than white people, with the lowest adherence to angiotensin-converting enzyme inhibitor treatment (South-Asian people: adjusted odds ratio 0.37, 95% CI 0.34-0.39; P<0.0001; Chinese people: adjusted odds ratio 0.50, 95% CI 0.47-0.54; P<0.0001) and statin therapy (South-Asian people: adjusted odds ratio 0.47, 95% CI 0.41 - 0.53, P < 0.0001; Chinese people: adjusted odds ratio 0.72, 95% CI 0.67 - 0.77; P<0.0001) compared with white people. CONCLUSION: Adherence to evidence-based pharmacotherapy was substantially worse among the South-Asian and Chinese populations. Care providers need to be alerted to the high levels of non adherence in these groups and the underlying causes need to be investigated. PMID- 25131337 TI - Toothbrushing after an erosive attack: will waiting avoid tooth wear? AB - The purpose of this study was to determine if storage for up to 4 h in human saliva results in a decrease of erosive tooth wear (ETW) and in an increase of surface microhardness (SMH) of enamel samples after an erosive attack with subsequent abrasion. Furthermore, we determined the impact of individual salivary parameters on ETW and SMH. Enamel samples were distributed into five groups: group 1 had neither erosion nor saliva treatment; groups 2-5 were treated with erosion, then group 2 was placed in a humid chamber and groups 3-5 were incubated in saliva for 30 min, 2 h, and 4 h, respectively. After erosion and saliva treatments, all groups were treated with abrasion. Surface microhardness and ETW were measured before and after erosion, incubation in saliva, and abrasion. Surface microhardness and ETW showed significant changes throughout the experiment: SMH decreased and ETW increased in groups 2-5, regardless of the length of incubation in saliva. The results of groups 3-5 (exposed to saliva) were not significantly different from those of group 2 (not exposed to saliva). Exposure of eroded enamel to saliva for up to 4 h was not able to increase SMH or reduce ETW. However, additional experiments with artificial saliva without proteins showed protection from erosive tooth wear. The recommendation to postpone toothbrushing of enamel after an erosive attack should be reconsidered. PMID- 25131340 TI - Auditory velocity discrimination in the horizontal plane at very high velocities. AB - We determined velocity discrimination thresholds and Weber fractions for sounds revolving around the listener at very high velocities. Sounds used were a broadband white noise and two harmonic sounds with fundamental frequencies of 330 Hz and 1760 Hz. Experiment 1 used velocities ranging between 288 degrees /s and 720 degrees /s in an acoustically treated room and Experiment 2 used velocities between 288 degrees /s and 576 degrees /s in a highly reverberant hall. A third experiment addressed potential confounds in the first two experiments. The results show that people can reliably discriminate velocity at very high velocities and that both thresholds and Weber fractions decrease as velocity increases. These results violate Weber's law but are consistent with the empirical trend observed in the literature. While thresholds for the noise and 330 Hz harmonic stimulus were similar, those for the 1760 Hz harmonic stimulus were substantially higher. There were no reliable differences in velocity discrimination between the two acoustical environments, suggesting that auditory motion perception at high velocities is robust against the effects of reverberation. PMID- 25131339 TI - Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of glioblastoma multiforme. AB - We report use of PEG-DSPE coated oxidized graphene nanoribbons (O-GNR-PEG-DSPE) as agent for delivery of anti-tumor drug Lucanthone (Luc) into Glioblastoma Multiformae (GBM) cells targeting base excision repair enzyme APE-1 (Apurinic endonuclease-1). Lucanthone, an endonuclease inhibitor of APE-1, was loaded onto O-GNR-PEG-DSPEs using a simple non-covalent method. We found its uptake by GBM cell line U251 exceeding 67% and 60% in APE-1-overexpressing U251, post 24h. However, their uptake was ~38% and 29% by MCF-7 and rat glial progenitor cells (CG-4), respectively. TEM analysis of U251 showed large aggregates of O-GNR-PEG DSPE in vesicles. Luc-O-GNR-PEG-DSPE was significantly toxic to U251 but showed little/no toxicity when exposed to MCF-7/CG-4 cells. This differential uptake effect can be exploited to use O-GNR-PEG-DSPEs as a vehicle for Luc delivery to GBM, while reducing nonspecific cytotoxicity to the surrounding healthy tissue. Cell death in U251 was necrotic, probably due to oxidative degradation of APE-1. PMID- 25131341 TI - Not too late to take vitamin D supplements. PMID- 25131342 TI - A colorimetric immunoassay for respiratory syncytial virus detection based on gold nanoparticles-graphene oxide hybrids with mercury-enhanced peroxidase-like activity. AB - A novel colorimetric immunoassay for highly sensitive detection of respiratory syncytial virus (RSV), one of the leading causes of severe lower respiratory tract infections in all age groups, has been proposed based on Hg(2+)-stimulated peroxidase-like activity of gold nanoparticles-graphene oxide (AuNPs-GO) hybrids. This metal ion-enhanced immunoassay shows high promise in the field of biomedical sciences. PMID- 25131344 TI - Controlling extreme events on complex networks. AB - Extreme events, a type of collective behavior in complex networked dynamical systems, often can have catastrophic consequences. To develop effective strategies to control extreme events is of fundamental importance and practical interest. Utilizing transportation dynamics on complex networks as a prototypical setting, we find that making the network "mobile" can effectively suppress extreme events. A striking, resonance-like phenomenon is uncovered, where an optimal degree of mobility exists for which the probability of extreme events is minimized. We derive an analytic theory to understand the mechanism of control at a detailed and quantitative level, and validate the theory numerically. Implications of our finding to current areas such as cybersecurity are discussed. PMID- 25131345 TI - Influence of genetic background on bleeding phenotype in the tail-tip bleeding model and recommendations for standardization: communication from the SSC of the ISTH. PMID- 25131343 TI - Treatment with melatonin after onset of experimental uveitis attenuates ocular inflammation. AB - BACKGROUND AND PURPOSE: Uveitis is a prevalent intraocular inflammatory disease and one of the most damaging ocular conditions. Pretreatment with melatonin prevented ocular inflammation induced by an intravitreal injection of bacterial LPS in the Syrian hamster. Here, we have assessed the anti-inflammatory effects of melatonin administered after the onset of ocular inflammation. EXPERIMENTAL APPROACH: The eyes of male Syrian hamsters were intravitreally injected with vehicle or LPS. Melatonin was injected i.p. every 24 h, starting 12 or 24 h after the LPS injection. A clinical evaluation (with a score index based on clinical symptoms), the number of infiltrating cells, protein concentration and PGE2 and PGF2alpha levels in the aqueous humour, as well as retinal NOS activity, lipid peroxidation and TNF-alpha levels were assessed. Retinal function was assessed by scotopic electroretinography, and light microscopy and immunohistochemistry were used to evaluate the state of the retinal structure. KEY RESULTS: Both treatment regimens with melatonin decreased clinical symptoms, reduced the leakage of cells and proteins, and decreased PG levels in aqueous humour from eyes injected with LPS. In addition, melatonin treatment blocked the decrease in scotopic electroretinogram a- and b-wave amplitude, protected the retinal structure and reduced the increase in NOS activity, lipid peroxidation and TNF-alpha levels, induced by LPS. CONCLUSIONS AND IMPLICATIONS: These results indicate that treatment with melatonin, starting after the onset of uveitis, attenuated ocular inflammation induced by LPS in the Syrian hamster and support the use of melatonin as a therapeutic resource for uveitis treatment. PMID- 25131346 TI - Iatrogenic right coronary artery stenosis resulting from surgical tricuspid valve replacement: case report and review of the literature. AB - Iatrogenic injury to the right coronary artery (RCA) is a rare complication of tricuspid valve surgery. We herein describe the first-ever report of RCA injury related to tricuspid valve replacement surgery. A 38-year-old man with recurrent tricuspid endocarditis underwent redo tricuspid valve replacement by means of a minimally invasive right thoracotomy with a 32-mm St. Jude bioprosthetic valve. His post-operative course was complicated by pulseless ventricular tachycardia requiring CPR and defibrillation. Cardiac catheterization revealed a "kinked" stenotic distal RCA. The lesion was noted to be flow limiting by fractional flow reserve and was treated with two everolimus-eluting stents. The RCA runs in the atrioventricular groove and is susceptible to injury especially in the region of the posterior leaflet of the tricuspid valve, where the relationship of the tricuspid annulus to the RCA is most intimate. Repair of surgically induced coronary stenosis can be accomplished with percutaneous intervention. PMID- 25131347 TI - The construction and legitimation of workplace bullying in the public sector: insight into power dynamics and organisational failures in health and social care. AB - Health-care and public sector institutions are high-risk settings for workplace bullying. Despite growing acknowledgement of the scale and consequence of this pervasive problem, there has been little critical examination of the institutional power dynamics that enable bullying. In the aftermath of large scale failures in care standards in public sector healthcare institutions, which were characterised by managerial bullying, attention to the nexus between bullying, power and institutional failures is warranted. In this study, employing Foucault's framework of power, we illuminate bullying as a feature of structures of power and knowledge in public sector institutions. Our analysis draws upon the experiences of a large sample (n = 3345) of workers in Australian public sector agencies - the type with which most nurses in the public setting will be familiar. In foregrounding these power dynamics, we provide further insight into how cultures that are antithetical to institutional missions can arise and seek to broaden the debate on the dynamics of care failures within public sector institutions. Understanding the practices of power in public sector institutions, particularly in the context of ongoing reform, has important implications for nursing. PMID- 25131349 TI - What's in this issue? PMID- 25131350 TI - Critical care nurses as dual agents: enhancing inter-professional collaboration or hindering patient advocacy? PMID- 25131348 TI - Fiber intake and plasminogen activator inhibitor-1 in type 2 diabetes: Look AHEAD (Action for Health in Diabetes) trial findings at baseline and year 1. AB - Plasminogen activator inhibitor 1 (PAI-1) is elevated in obese individuals with type 2 diabetes and may contribute, independently of traditional factors, to increased cardiovascular disease risk. Fiber intake may decrease PAI-1 levels. We examined the associations of fiber intake and its changes with PAI-1 before and during an intensive lifestyle intervention (ILI) for weight loss in 1,701 Look AHEAD (Action for Health in Diabetes) participants with dietary, fitness, and PAI 1 data at baseline and 1 year. Look AHEAD was a randomized cardiovascular disease trial in 5,145 overweight/obese patients with type 2 diabetes, comparing ILI (goal of >=7% reduction in baseline weight) with a control arm of diabetes support and education. ILI participants were encouraged to consume vegetables, fruits, and grain products low in sugar and fat. At baseline, median fiber intake was 17.9 g/day. Each 8.3 g/day higher fiber intake was associated with a 9.2% lower PAI-1 level (P=0.008); this association persisted after weight and fitness adjustments (P=0.03). Higher baseline intake of fruit (P=0.019) and high-fiber grain and cereal (P=0.029) were related to lower PAI-1 levels. Although successful in improving weight and physical fitness at 1 year, the ILI in Look AHEAD resulted in small increases in fiber intake (4.1 g/day, compared with -2.35 g/day with diabetes support and education) that were not related to PAI-1 change (P=0.34). Only 31.3% of ILI participants (39.8% of women, 19.1% of men) met daily fiber intake recommendations. Increasing fiber intake in overweight/obese individuals with diabetes interested in weight loss is challenging. Future studies evaluating changes in fiber consumption during weight loss interventions are warranted. PMID- 25131356 TI - Effect of intravenous infusion of dobutamine hydrochloride on the development of early postoperative cognitive dysfunction in elderly patients via inhibiting the release of tumor necrosis factor-alpha. AB - To investigate the effects of dobutamine hydrochloride on early postoperative cognitive dysfunction (POCD) and plasma tumor necrosis factor (TNF)-alpha concentration in patients undergoing hip arthroplasty, 124 patients undergoing unilateral total hip arthroplasty, aged 70-92 years old, were randomly assigned to four groups (n=31) as follows: a control group of patients receiving only saline (intravenous infusion, i.v.); and groups receiving 2, 4, or 6MUgkg(-1)min( 1) (i.v.) of dobutamine hydrochloride. Cognitive functions were assessed on the day before surgery (T1), and the 1st day (T2), 3rd day (T3), and 7th day (T4) postsurgery using the Mini Mental State Examination (MMSE). The plasma TNF-alpha protein level was determined 10min before anesthesia (Ta), and 10min (Tb), 30min (Tc), and 60min (Td) after anesthesia by an enzyme-linked immunosorbent assay. Cognitive disorder was observed within the first 3 days after hip arthroplastic surgery, and it had recovered 7 days after the operation in the control group of patients. Administration of 2 or 4MUgkg(-1)min(-1) dobutamine hydrochloride was able to reverse the early POCD. Simultaneously, an increase of plasma TNF-alpha levels 30min after anesthesia was observed (41.34+/-9.61 vs. 27.75+/-5.45), which was significantly suppressed by the administration of low-dose dobutamine hydrochloride (29.23+/-7.32 vs. 41.34+/-9.61) but not by high-dose dobutamine hydrochloride (45.9+/-12.11 vs. 41.34+/-9.61). Together, our data indicated that the plasma concentration of TNFalpha was engaged in the effect of dobutamine hydrochloride on POCD. PMID- 25131357 TI - A matter of trial and error for motor learning. AB - Climbing fiber inputs to cerebellar Purkinje cells are thought to carry error signals that can trigger motor learning across multiple time scales. A new study by Kimpo et al. finds that the potency of climbing fibers as instructive signals for adaptation of the vestibulo-ocular reflex depends on task conditions. PMID- 25131358 TI - Basal ganglia: racing to say no. AB - How we choose one action over another has intrigued neuroscientists for decades. Early models of decision-making involved a race between processes representing alternative choices. To explain behaviour in complex decisions, for example, where one must cancel an impending action, a Stop unit must also join the race. Recent neuronal recordings have demonstrated just such a race between Go and Stop processes in the basal ganglia. This is a landmark advance because it neurophysiologically justifies the need for a Stop process in such tasks, and very likely in other behaviours requiring rapid cancellation of impending actions. PMID- 25131360 TI - Livedoid vasculopathy (LV) associated with sticky platelets syndrome type 3 (SPS type 3) and enhanced activity of plasminogen activator inhibitor (PAI-1) anomalies. PMID- 25131361 TI - Primary cutaneous anaplastic large cell lymphomas with 6p25.3 rearrangement exhibit particular histological features. AB - AIMS: CD30-positive primary cutaneous lymphoproliferative disorders include several entities with differing clinical presentation but overlapping histological features, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (C-ALCL). DUSP22-IRF4 locus translocation is present in 20-57% of C-ALCLs, and has also been described in a series of 11 lymphomatoid papulosis patients, where it was associated with a particular biphasic histological pattern, including pagetoid reticulosis-type epidermal infiltration. We aimed to study whether the presence of this translocation may define distinctive histological features in C-ALCL. METHODS AND RESULTS: We collected three cases of C-ALCL with histological features similar to those described in the new variant of lymphomatoid papulosis with 6p25.3 rearrangement. We studied their histological features and immunophenotype, using a panel of antibodies against CD30, TCR-betaF1, TCR-gamma, CD4, CD8, CD20, Ki-67 and ALK. FISH analyses were performed using an IRF4-DUSP22 break-apart probe for the study of the 6p25.3 rearrangement. FISH results were positive in the three cases, which all showed distinctive histological and immunohistochemical features: a diffuse dermal infiltrate of atypical medium-to-large cells, and marked epidermotrophism with small, atypical intra-epidermal lymphocytes. CONCLUSIONS: Our findings suggest that the presence of 6p25.3 rearrangement might be related to this particular biphasic pattern. PMID- 25131362 TI - [Extrapulmonary tuberculosis]. AB - Each year, there are more than eight million new cases of tuberculosis and 1.3 million deaths. There is a renewed interest in extrapulmonary forms of tuberculosis as its relative frequency increases. Among extrapulmonary organs, pleura and lymph nodes are the most common. Their diagnosis is often difficult and is based on clinical, radiological, bacteriological and histological findings. Extrapulmonary lesions are paucibacillary and samplings, in most cases, difficult to obtain, so diagnosis is often simply presumptive. Nucleic acid amplification tests, which are fast and specific, have greatly facilitated the diagnosis of some forms of extrapulmonary tuberculosis. However, their sensitivity is poor and a negative test does not eliminate the diagnosis. Treatment is the same as for pulmonary forms, but its duration is nine to 12 months for central nervous system and for bone tuberculosis. Corticosteroids are indicated in meningeal and pericardial localizations. Complementary surgery is used for certain complicated forms. PMID- 25131363 TI - [Diaphragmatic bronchogenic cyst: an exceptional location]. AB - A 64-year-old man complained of persistent dyspnea and bilateral basi-thoracic pain with shoulder irradiation. Chest computed tomography revealed a heterogeneous left diaphragmatic mass, while magnetic resonance imaging showed hypo-T1 and hyper-T2 signal. Positron-emission tomography did not show any hypermetabolism. Video-assisted thoracic surgery was decided. At inspection, tumour appeared within the posterior costal part of the diaphragmatic muscle. Tumour resection was extended to a 8-cm-long portion of the lumbar part of diaphragm. Diaphragm was repaired with non-absorbable interrupted sutures. Postoperative course was uneventful. Final pathology revealed an intra diaphragmatic bronchogenic cyst, which is an exceptional condition. Primary diaphragmatic tumours are very rare and preoperative diagnosis cannot be affirmed. Embryologic hypotheses (migration along the oesophagus or envelopment within diaphragmatic precursors of an abnormal supernumerary lung bud) including recent molecular findings of deregulated pathways (fibroblast growth factor-10 and NOTCH) are discussed. PMID- 25131364 TI - [Sarcoidose in patient with chronic hepatitis C treated with pegylated interferon]. AB - Induced sarcoidosis during therapy with interferon for chronic viral hepatitis C involves mainly by isolated cutaneous lesions or with lung lesions. Systemic forms are very rare. We report an observation. A 50-year-old patient developed a systemic sarcoidosis two months after the end of treatment for hepatitis C with pegylated interferon and ribavirin with lung, joint and hepatic manifestations. After starting corticosteroid therapy, the evolution was favourable. Induced sarcoidosis by interferon therapy is rare, treatment necessitates stopping interferon, and sometimes corticosteroid therapy. PMID- 25131359 TI - Control of neural circuit formation by leucine-rich repeat proteins. AB - The function of neural circuits depends on the precise connectivity between populations of neurons. Increasing evidence indicates that disruptions in excitatory or inhibitory synapse formation or function lead to excitation/inhibition (E/I) imbalances and contribute to neurodevelopmental and psychiatric disorders. Leucine-rich repeat (LRR)-containing surface proteins have emerged as key organizers of excitatory and inhibitory synapses. Distinct LRR proteins are expressed in different cell types and interact with key pre- and postsynaptic proteins. These protein interaction networks allow LRR proteins to coordinate pre- and postsynaptic elements during synapse formation and differentiation, pathway-specific synapse development, and synaptic plasticity. LRR proteins, therefore, play a critical role in organizing synaptic connections into functional neural circuits, and their dysfunction may contribute to neuropsychiatric disorders. PMID- 25131365 TI - [Place and role of the pleura in non-small cell lung cancer dissemination]. AB - INTRODUCTION: The pleural involvement (PLI) in non-small cell lung cancer (NSCLC) has a poor prognosis, even though it might be very heterogeneous. PATIENTS AND METHODS: A multicentric retrospective descriptive study was performed over 2329 patients who were operated for NSCLC between 1979 and 2010. The patients with PLI were classified in P(Parietal)PLI and V(visceral)PLI and then each subdivided : VPLI to peripheric (VPLI-P) and fissural (VPLI-F) and PPLI to mediastinal (PPLI M) and costal (PPLI-C). Characteristics and survival were compared between the subgroups as well as with patients without PLI (WPLI, n=1439). RESULTS: The sex ratio was 2.8 (males: n=1713). The PLI patients were significantly younger, with a less sex-ratio, less R0 resections (96% versus 98.7%, P=0.000076), and less N0 (60% vs 70%, P<10(-6)) as their 5-year survival (45.7% vs 55.5%, P<10(-6)). The PLI was related to the size of NSCLC (P<10(-6)) and N2 involvement (P=0.0020). It was less frequent after neoadjuvant treatment (36.2% vs 39.1% P=0.03). In the VPLI-F or PPLI-M, pneumonectomies were more frequent (P<10(-6)). In VPLI-P (n=196/561), there were more pN1 and pN2 (P=0.0065) with a 5-year survival of 42.9% vs 54.4%, P=0.013. In multivariate analysis, the PLI was not an independent prognostic factor contrary to age, sex, type of resection, pT and pN. CONCLUSION: The pleura play a major role in NSCLC dissemination. Its involvement affects pN, the type of surgical resection and justifies the use of neoadjuvant treatment. PMID- 25131366 TI - [Lung cancer surgery in solid organ transplanted patients]. AB - BACKGROUND: The incidence of lung cancer is reputed to be higher and prognosis worse in solid organ transplant recipients than in the general population. Our purpose was to review the results of surgery in this group of patients. METHODS: We retrospectively reviewed 49 male and 6 female patients; mean aged 60.6 years (38-85). Transplanted organ was heart (n = 37), kidney (n=12), liver (n = 5) and both-lungs (n = 1); 48 patients had smoking habits and 42 heavy comorbidities (76.4%). Lung cancer was diagnosed during surveillance (78.2%, n = 43) or because of symptoms (21.8%, n = 12). We reviewed TNM and other main characteristics, among them histology (squamous-cell-carcinoma n = 23, adenocarcinomas n = 24, others n = 8). RESULTS: Surgery consisted of: exploratory thoracotomy (n = 2), wedge resections (n = 6), segmentectomy (n = 1), lobectomy (n = 42), pneumonectomy (n = 4). Postoperative mortality was 7.4% (n = 4) and complication rate 34.5% (n = 19). Five-year survival rate was 46.4% (65.4% for stage I patients, n = 25). Among the 35 dead patients during follow-up, 14 died of their lung cancer (40%). Two had been re-operated from another lung cancer: one after 3 and 8 years who survived 16 years, and the other after 2 years who survived 70 months. CONCLUSIONS: Surgery results are good and postoperative events acceptable despite theoretically increased risks. This also supports performing a close follow-up of transplanted patients and particularly those with smoking history in view of detecting lung cancer appearing at an early stage. PMID- 25131367 TI - [Epidemiology of tuberculosis]. AB - Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis. It represents, according to World Health Organization (WHO), one of the most leading causes of death worldwide. With nearly 8 million new cases each year and more than 1 million deaths per year, tuberculosis is still a public health problem. Despite of the decrease in incidence, morbidity and mortality remain important partially due to co-infection with human immunodeficiency virus and emergence of resistant bacilli. All WHO regions are not uniformly affected by TB. Africa's region has the highest rates of morbidity and mortality. The epidemiological situation is also worrying in Eastern European countries where the proportion of drug-resistant tuberculosis is increasing. These regional disparities emphasize to develop screening, diagnosis and monitoring to the most vulnerable populations. In this context, the Stop TB program, developed by the WHO and its partner's, aims to reduce the burden of disease in accordance with the global targets set for 2015. PMID- 25131368 TI - [Pneumonectomy for benign disease: indication and factors affecting the postoperative course]. AB - Pneumonectomy for benign disease is rare but may generate more postoperative morbimortality than when performed for lung cancer. We questioned this assessment and retrospectively reviewed 1436 pneumonectomies and 54 completions of which 82 and 10 performed for benign disease (5.7% and 18.5%, respectively): left n=65 and right n=27. Indications were: post-tuberculosis destroyed lung (n=37), aspergilloma (n=18), bronchiectasis (n=19), infection (n=5), congenital malformations (n=5), inflammatory pseudotumor (n=3), trauma (n=2), post-radiation (n=2) and mucormycosis (n=1). Pneumonectomy consisted of 48 standard and 44 pleuro-pneumonectomies. Stump coverage by flaps was performed in 66.3% (61/92). Complications occurred in 21.7% (20/92) and postoperative deaths in 7.6% (7/92, of which 5 with fungal infections), which was not different than what was observed in lung cancer. There was no difference in fistula formation and mortality regarding the side, the type of resection and the protective role of stump coverage. Considering patients with fungal infections versus others, mortality was 26.3% (n=5/19) and 2.7% (n=2/74), respectively (P=0.0028). Pneumonectomy for benign disease achieves cure with acceptable mortality and morbidity. However, presence of fungal infection should raise the attention for possibility of increased postoperative risks. PMID- 25131369 TI - [Tracheal tumor treated as asthma]. AB - Primary tumors of the trachea are very rare. In adults, the majority of them are malignant. Schwannomas are exceedingly rare benign tumors in the tracheobronchial tree. We report a case of a 37-year-old man who was hospitalized for increasing dyspnea. He had been treated for bronchial asthma for the last 4 years with no benefit. The CT scan of the chest and bronchoscopy identified a tracheal mass that was prolapsed in the left stem bronchus. The patient did not remain free of disease after endoscopic laser resection. So, surgical resection was made. The tumor was excised at its base. A segment of the left stem bronchus was removed and primary anastomosis was performed. The histopathologic diagnosis was of a benign schwannoma without malignant elements. There was no recurrence during the follow-up period. This case demonstrates that intratracheal masses should be considered in patients with dyspnea or in patients with asthma refractory to conventional therapy. PMID- 25131370 TI - [Disseminated tuberculosis following infliximab therapy for Crohn disease: a case report]. AB - Anti-tumor necrosis factor (TNF) therapy has been the major advance in the treatment of inflammatory bowel disease, especially Crohn's disease. But there is a higher risk of infections, especially tuberculosis (TB), in patients treated with anti-TNFalpha. The authors report a case of disseminated tuberculosis with the following features: pulmonary tuberculosis, left supra clavicular cervical and meditational lymphadenopathy, bilateral pleural effusion, peritoneal and splenic involvement. This disseminated tuberculosis was observed in a 39-year-old woman who was treated by infliximab for refractory Crohn's disease. The evolution with antituberculosis drugs was fatal, the death of the patient was due to hepatic encephalitis. CONCLUSION: The physicians should always be aware in the use of TNF-alpha blockers according to guidelines. Its recommended to realize a complete pretherapeutic assessment and it is necessary to follow-up the patients to detect possible reactivation of latent tuberculosis. PMID- 25131371 TI - [Major pulmonary resections for lung cancer and thoracoscopic approach: some reflections on published data]. AB - Video-assisted thoracic surgery has a renewed topicality in treating early stage non-small cell lung cancer. Numerous publications show the benefits of this surgical technique in comparison with conventional thoracotomy. However, some surgeons are still apprehensive for its validity in lung cancer. Few works were dedicated to the critical aspect of this new technique which generates silent controversy and is far from having the general approval of all surgical teams. A critical review of several papers disclosed some concerns related to this approach, notably the risk of intra-operative technical problems and the possibility of questionable results concerning cancer dissection and clearance. A randomized clinical trial is now mandatory to confirm the safety and usefulness of this technique. PMID- 25131372 TI - [Primitive lung abscess: an unusual situation in children]. AB - INTRODUCTION: Lung abscess is a localized area of non tuberculosis suppurative necrosis of the parenchyma lung, resulting in formation of a cavity containing purulent material. This pathology is uncommon in childhood. CASE REPORT: A 3-year 6 month-old boy was admitted with prolonged fever and dyspnea. Chest X-ray showed a non systemized, well limited, thick walled, hydric, and excavated opacity containing an air-fluid level. Chest ultrasound examination showed a collection of 6. 8 cm of diameter in the right pulmonary field with an air-fluid level. Hemoculture showed Staphylococcus aureus. The patient received large spectrum antibiotherapy. Three days after, he presented a septic shock and surgical drainage was indicated. Histological examination confirmed the diagnosis of lung abscess. Any underlying condition such as inoculation site, local cause or immune deficiency, was noted and diagnosis of primary abscess was made. The patient demonstrated complete recovery. He is asymptomatic with normal chest X-ray and pulmonary function after 3 years of evolution. CONCLUSION: Lung abscess represent a rare cause of prolonged fever in childhood. An underlying condition must be excluded to eliminate secondary abscess. PMID- 25131375 TI - Small RNA and degradome profiling reveals a role for miRNAs and their targets in the developing fibers of Gossypium barbadense. AB - microRNAs (miRNAs) are 20-24 nucleotide non-coding small RNAs that play important roles in plant development. The stages of cotton fiber development include initiation, elongation, secondary wall thickening (SWT) and maturation. We constructed seven fiber RNA libraries representing the initiation, elongation and SWT stages. In total, 47 conserved miRNA families and seven candidate miRNAs were profiled using small RNA sequencing. Northern blotting and real-time polymerase chain reaction (PCR) analyses revealed the dynamic expression of miRNAs during fiber development. In addition, 140 targets of 30 conserved miRNAs and 38 targets of five candidate miRNAs were identified through degradome sequencing. Analysis of correlated expression between miRNAs and their targets demonstrated that specific miRNAs suppressed the expression of transcription factors, SBP and MYB, a leucine-rich receptor-like protein kinase, a pectate lyase, alpha-tubulin, a UDP-glucuronic acid decarboxylase and cytochrome C oxidase subunit 1 to affect fiber development. Histochemical analyses detected the biological activity of miRNA156/157 in ovule and fiber development. Suppressing miRNA156/157 function resulted in the reduction of mature fiber length, illustrating that miRNA156/157 plays an essential role in fiber elongation. PMID- 25131373 TI - Early diagnosis of Gaucher disease in pediatric patients: proposal for a diagnostic algorithm. AB - Gaucher disease (GD) is caused by an enzyme deficiency that leads to the accumulation of glycolipids in various organs. Although the signs and symptoms of GD emerge in childhood in the majority of patients, the disease often remains unrecognized for many years with delay of benefits of therapy or development of irreversible complications. Based on published data and data from the International Collaborative Gaucher Group Registry, an algorithm has been drafted for early diagnosis of GD in pediatric patients. It will help hematologists in promoting a timely diagnosis and early access to therapy for pediatric patients with GD. PMID- 25131376 TI - Sonography in carpal tunnel syndrome with normal nerve conduction studies. AB - INTRODUCTION: We assessed the yield of high-resolution ultrasonography (HRUS) in patients with clinically definite carpal tunnel syndrome (CTS) and normal nerve conduction studies (NCS). METHODS: This blinded, prospective, cross-sectional study involved 35 patients (60 hands) with clinically definite CTS and normal NCS, and 20 controls (40 hands). Cross-sectional area (CSAs) of the median nerve at the level of the pisiform bone and flexor retinaculum thickness (FRT) were measured. RESULTS: CSA was abnormal in 48.6% of patients (confidence interval 32.0-65.2%, P = 0.95). FRT was increased in only 34.3% (18.3-49.7%), but was independently abnormal in 2 patients. CSA abnormalities correlated with positive provocative tests and sensory loss. The HRUS changes were mild. CONCLUSIONS: HRUS confirms clinically diagnosed CTS in about half of the patients with normal NCS. PMID- 25131377 TI - Alleviation of respiratory syncytial virus replication and inflammation by fungal immunomodulatory protein FIP-fve from Flammulina velutipes. AB - Respiratory syncytial virus (RSV) causes bronchiolitis in children followed by inflammation and asthma-like symptoms. The development of preventive therapy for this virus continues to pose a challenge. Fungal immunomodulatory proteins (FIPs) exhibit anti-inflammatory function. FIP-fve is an immunomodulatory protein isolated from Flammulina velutipes. To determine whether FIP-fve affects the infection or consequence of immunity of RSV, we investigated viral titers of RSV and inflammatory cytokine levels in vivo and in vitro. Oral FIP-fve decreased RSV induced airway hyperresponsiveness (AHR), airway inflammation, and IL-6 expression in bronchoalveolar lavage fluid (BALF) of BALB/c mice. RSV replication and interleukin 6 (IL-6) levels in RSV-infected HEp-2 cells were compared before and after FIP-fve treatment. FIP-fve inhibited viral titers on plaque assay and Western blot, as well as inhibited RSV-stimulated expression of IL-6 on ELISA and RT-PCR. The results of this study suggested that FIP-fve decreases RSV replication, RSV-induced inflammation and respiratory pathogenesis. FIP-fve is a widely used, natural compound from F.velutipes that may be a safe agent for viral prevention and even therapy. PMID- 25131378 TI - Modulation of inflammation and pathology during dengue virus infection by p38 MAPK inhibitor SB203580. AB - Dengue virus (DENV) infection could lead to dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The disease outcome is controlled by both viral and host factors. Inflammation mediators from DENV-infected cells could contribute to increased vascular permeability, leading to severe DHF/DSS. Therefore, suppression of inflammation could be a potential therapeutic approach for treatment of dengue patients. In this context, p38 MAPK (mitogen-activated protein kinase) is a key enzyme that modulates the initiation of stress and inflammatory responses. Here we show that SB203580, a p38 MAPK inhibitor, suppressed the over production of DENV-induced pro-inflammatory mediators such as TNF-alpha, IL-8, and RANTES from human PBMCs, monocytic THP-1, and granulocyte KU812 cell lines. Oral administration of SB203580 in DENV-infected AG129 mice prevented hematocrit rise and lymphopenia, limited the development of inflammation and pathology (including intestine leakage), and significantly improved survival. These results, for the first time, have provided experimental evidence to imply that a short term inhibition of p38 MAPK may be beneficial to reduce disease symptoms in dengue patients. PMID- 25131379 TI - Anti-lipopolysaccharide factor isoform 3 from Penaeus monodon (ALFPm3) exhibits antiviral activity by interacting with WSSV structural proteins. AB - In innate immunity, antimicrobial peptides (AMPs) play a vital role in combating microbial pathogens. Among the AMPs identified in Penaeus monodon, only anti lipopolysaccharide factor isoform 3 (ALFPm3) has been reported to exhibit activity against white spot syndrome virus (WSSV). However, the mechanism(s) involved are still not clear. In the present study, ALFPm3-interacting proteins were screened for from a WSSV library using the yeast two-hybrid screening system, revealing the five potential ALFPm3-interacting proteins of WSSV186, WSSV189, WSSV395, WSSV458 and WSSV471. Temporal transcriptional analysis in WSSV infected P. monodon revealed that all five of these WSSV gene transcripts were expressed in the late phase of infection (24h and 48h post-infection). Of these, WSSV189 that was previously identified as a structural protein, was selected for further analysis and was shown to be an enveloped protein by Western blot and immunoelectron microscopy analyses. The in vitro pull-down assay using recombinant WSSV189 (rWSSV189) protein as bait confirmed the interaction between ALFPm3 and WSSV189 proteins. Moreover, pre-incubation of rWSSV189 protein with rALFPm3 protein interfered with the latter's neutralization effect on WSSV in vivo, as shown by the increased cumulative mortality of shrimp injected with WSSV following prior treatment with pre-incubated rWSSV189 and rALFPm3 proteins compared to that in shrimp pre-treated with rALFPm3 protein. Thus, ALFPm3 likely performs its anti-WSSV action by binding to the envelope protein WSSV189 and possibly other WSSV structural proteins. PMID- 25131380 TI - Homing effect of adipose-derived stem cells to the injured liver: the shift of stromal cell-derived factor 1 expressions. AB - BACKGROUND: Whether systemically transplanted human adipose-derived stem cells (ADSCs) homed to the injured liver in nude mice under stress with subsequent hepatectomy (Hx) and ischemia-reperfusion (I/R) was investigated in the present study. The types of cells in the liver that were involved in the homing of ADSCs were clarified, with focus on the stromal-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR-4) axis. METHODS: Adipose-derived stem cells were transplanted intravenously immediately after 70% Hx and I/R. ADSCs were traced by in vivo imaging for 24 h after transplantation and ADSCs were histologically detected in the liver. SDF-1 and CXCR-4 expressions in the liver were evaluated by real time RT-PCR. The immunohistochemical analysis of SDF-1 was also performed to identify SDF-1 expressing cells in the liver. RESULTS: Adipose-derived stem cells were found in various organs immediately following transplantation and almost accumulated in remnant liver or spleen at 6 h after transplantation. ADSCs were also histologically revealed in the harvested liver. Hx and I/R injury significantly enhanced SDF-1 expressions regardless of ADSCs transplantation, and only ADSC transplantation increased CXCR-4 expressions. The predominant SDF-1 positive cells in the liver were equally identified in parenchymal and non parenchymal cells at 6 h, but shifted to non-parenchymal cells at 24 h after transplantation. CONCLUSIONS: Systemically transplanted ADSCs homed to the injured liver after transplantation, possibly based on the mechanisms of SDF 1/CXCR-4 axis. Therefore, systemic transplantation might be an effective and practical route for the transplantation of ADSCs. PMID- 25131381 TI - Sustaining dignity? food insecurity in homeless young people in urban Australia. AB - ISSUE ADDRESSED: Food insecurity is recognised as an increasing problem in disadvantaged and marginalised groups. The aim of this study was to investigate issues associated with food insecurity and nutrition in young people experiencing, or at risk of, homelessness in metropolitan Australia. METHODS: Eight focus group discussions were conducted with 48 young people (aged between 15 and 25 years) in specialist homelessness services in central and south-western Sydney. RESULTS: Participants described daily experiences of food insecurity, persistent hunger and poverty. Structural barriers to food security and nutrition were identified and included poverty and reduced physical access to fresh foods. Participants also described a desire to save time, for convenience and to be socially connected. Despite the hardships and the chaos of youth homelessness, the groups were defined by their strength of character, resilience and hope for the future. CONCLUSION: Homeless young people within central and south-western Sydney report varying degrees of food insecurity, despite being supported by specialist youth homelessness services. SO WHAT? A collaborative, multistrategic approach with youth participation is required to further enhance the capacity of youth services to improve food security, food access and the availability of nutritious foods for homeless young people. A greater focus on advocacy and policy action is also required to bring food security and nutrition to the forefront of national efforts to improve the health and welfare of disadvantaged groups. PMID- 25131382 TI - Evolutionary ecology of microsporidia associated with the invasive ladybird Harmonia axyridis. AB - Invasive species are characterized by the rapid growth and spread of their populations after establishing a foothold in new habitats, and there are now many examples of such species negatively affecting biodiversity and the economy. It is unclear why some species can become successful invaders, whereas most (even if closely related) remain noninvasive. We previously proposed a hypothesis that parasites associated with invading species can promote their invasive success if they are harmless toward the invaders but harmful to their competitors and/or predators in the newly colonized habitat. Here we discuss whether microsporidia that have recently been discovered in the invasive ladybird Harmonia axyridis contribute to its invasive success. We show that all H. axyridis beetles sourced from diverse collection sites all over the world carry abundant microsporidia. This suggests that both native and invasive H. axyridis populations are associated with these tolerated parasites, which were likely to have existed in native populations before expansion rather than being acquired in newly colonized areas. We describe the pathogenesis of the microsporidia during different developmental stages of H. axyridis and we address the possibility that the predation of its infected eggs and larvae by competing native ladybird species may lead to their infection and ultimately to their decline. Finally, we discuss our initial hypothesis: microsporidia that are tolerated by an invasive vector insect can be active against susceptible native competitors and/or predator species. PMID- 25131383 TI - Purification and characterization of alpha-acetolactate decarboxylase (ALDC) from newly isolated Lactococcus lactis DX. AB - BACKGROUND: Diacetyl (2,3-butanedione) is a common flavor aroma from fermented dairy products. There is a need to screen new microorganisms that can efficiently produce large amounts of diacetyl. RESULTS: A new lactic acid bacterium that produced high concentrations of diacetyl was identified based on Gram staining, microscopic examination and 16S rDNA sequence analysis as Lactococcus lactis DX. Its alpha-acetolactate decarboxylase (ALDC) was purified using 0.45 g mL(-1) ammonium sulfate precipitation, Sephacryl S-300 and S-200 HR and native-PAGE. The purified ALDC displayed a monomer structure and had a molecular mass of about 73.1 kDa, which was estimated using SDS-PAGE. IR analysis showed that the ALDC had a typical protein structure. The optimal temperature and pH for ALDC activity were 40 degrees C and 6.5 respectively. The ALDC of L. lactis DX was activated by Fe(2+) , Zn(2+) , Mg(2+) , Ba(2+) and Ca(2+) , while Cu(2+) significantly inhibited ALDC activity. Leucine, valine and isoleucine activated the ALDC. CONCLUSION: A strain that had high ability to produce diacetyl was identified as L. lactis DX. The difference in diacetyl production may be due to the ALDC, which is different from other ALDCs. PMID- 25131384 TI - Discoveries of hydrogen sulfide as a novel cardiovascular therapeutic. AB - Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule that elicits a number of cytoprotective effects in mammalian species. H2S was originally considered toxic at elevated levels, but 15 years ago the labile molecule was discovered in mammalian tissue and termed a gasotransmitter, thus opening the door for research aimed towards understanding its physiologic nature. Since then, novel findings have depicted the beneficial aspects of H2S therapy, such as vasodilation, antioxidant upregulation, inflammation inhibition, and activation of anti-apoptotic pathways. These cytoprotective alterations effectively treat multiple forms of cardiac injury at the preclinical level of research. The field has progressed towards instituting novel H2S donors that prove more effective at activating the subsequent cardioprotective enhancements over longer time periods. As more findings explore the efficacy of H2S, research focused on detection of sulfhydrated targets is on the rise. Understanding the molecular mechanisms that stem from H2S treatment may lead the field towards powerful therapeutics in the clinical setting. This review will discuss the cytoprotective and cardioprotective effects of H2S therapy, provide analysis on the molecular alterations that lead to these enhancements, and explore recently developed therapeutics that may bring this gasotransmitter into the clinic in the near future. PMID- 25131385 TI - Biobased building blocks for the rational design of renewable block polymers. AB - Block polymers (BPs) derived from biomass (biobased) are necessary components of a sustainable future that relies minimally on petroleum-based plastics for applications ranging from thermoplastic elastomers and pressure-sensitive adhesives to blend compatibilizers. To facilitate their adoption, renewable BPs must be affordable, durable, processable, versatile, and reasonably benign. Their desirability further depends on the relative sustainability of the renewable resources and the methods employed in the monomer and polymer syntheses. Various strategies allow these BPs' characteristics to be tuned and enhanced for commercial applications, and many of these techniques also can be applied to manipulate the wide-ranging mechanical and thermal properties of biobased and self-assembling block polymers. From feedstock to application, this review article highlights promising renewable BPs, plus their material and assembly properties, in support of de novo design strategies that could revolutionize material sustainability. PMID- 25131386 TI - Protective effect of ((4-tert-butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide, a novel unsymmetrical divinyl sulfide, on an oxidative stress model induced by sodium nitroprusside in mouse brain: involvement of glutathione peroxidase activity. AB - OBJECTIVES: In this study, the antioxidant action of ((4-tert butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide, a novel unsymmetrical divinyl sulfide, against oxidative damage induced by sodium nitroprusside (SNP) in brains of mice was investigated. METHODS: Mice received SNP (0.335 MUmol/site, intracerebroventricular) 30 min after administration of sulfide (10 mg/kg, intragastrically). After 1 h, animals were sacrificed and the brains were removed to biochemistry analysis. Thiobarbituric acid reactive species (TBARS), protein carbonyl (PC) and non-protein thiol (NPSH) levels, as well as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities were determined. KEY FINDINGS: SNP increased TBARS and PC levels, CAT, GPx, GR and GST activities and reduced NPSH levels. Administration of the sulfide attenuated the changes produced by SNP and increased per se GPx activity in brains of mice. Toxicological parameters revealed that this compound did not cause acute renal or hepatic damage. CONCLUSIONS: In conclusion, ((4-tert-butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide protected against oxidative damage caused by SNP in mouse brain. GPx activity is involved, at least in part, in the cerebral antioxidant action of this compound. PMID- 25131387 TI - Bone formation in peri-implant defects grafted with microparticles: a pilot animal experimental study. AB - AIM: This study aimed to evaluate the healing of peri-implant defects grafted with microparticles (MPs). MATERIAL AND METHODS: Six domestic pigs received nine standardized defects at the calvaria, and an implant was inserted in the middle of each defect. The space between the implant and lateral bone portion was filled with MP pellets (n = 18) or MP supernatant (n = 18) or left unfilled (n = 18). After 14 and 28 days, three animals were sacrificed and specimens removed for further processing. Samples were microradiographically and histologically analysed. In addition, we immunohistochemically stained for anti-vWF as a marker of angiogenesis. RESULTS: In the case of bone regeneration and vessel formation, the null hypothesis can be partially rejected. After 14 and 28 days, no significant difference was observed within groups regarding de novo bone formation, bone density and osseointegration. However, superior vessel formation was found at both time points. CONCLUSION: Microparticles represent a promising treatment option to accelerate peri-implant vessel formation. Further studies are needed to investigate the regenerative properties of MPs more precisely. PMID- 25131388 TI - Correlation of plasma brain-derived neurotrophic factor and metabolic profiles in drug-naive patients with bipolar II disorder after a twelve-week pharmacological intervention. AB - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of bipolar disorder (BD) and metabolic syndrome. We investigated the correlation between plasma BDNF with mood symptoms and metabolic indices in patients with BD-II over a 12-week pharmacological intervention. METHOD: Drug-naive patients with BD-II (n=117) were recruited. Metabolic profiles [cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI)] and plasma BDNF wtrun "tblautotrun "tblsctrun "tbl_contere measured at baseline and 2, 8, and 12 weeks after beginning medication. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. RESULTS: Seventy-six (65.0%) patients completed the intervention. Plasma BDNF levels were significantly associated with BMI (P=9.6E-5), low-density lipoprotein (P=0.034) and total (P=0.001) cholesterol, but not with the Hamilton Depression Rating Scale-17 and Young Mania Rating Scale scores over the 12-week treatment. CONCLUSION: We found initial evidence of a positive correlation between plasma BDNF levels and BMI, low-density lipoprotein and total cholesterol in drug-naive patients with BD-II. The specific function of BDNF in regulating and maintaining peripheral metabolic health requires additional investigation. PMID- 25131389 TI - Minimally Invasive Early Operative Treatment of Progressive Foot and Ankle Deformity Associated With Charcot-Marie-Tooth Disease. AB - Charcot-Marie-Tooth disease is a neuromuscular disorder that commonly results in a predictable pattern of progressive bilateral lower extremity weakness, numbness, contracture, and deformity, including drop foot, loss of ankle eversion strength, dislocated hammertoes, and severe cavus foot deformity. Late stage reconstructive surgery will be often necessary if the deformity becomes unbraceable or when neuropathic ulcers have developed. Reconstructive surgery for Charcot-Marie-Tooth deformity is generally extensive and sometimes staged. Traditional reconstructive surgery involves a combination of procedures, including tendon lengthening or transfer, osteotomy, and arthrodesis. The described technique highlights our early surgical approach, which involves limited intervention before the deformity becomes rigid, severe, or disabling. We present 2 cases to contrast our early minimally invasive technique with traditional late stage reconstruction. Charcot-Marie-Tooth disease affects different muscles at various stages of disease progression. As 1 muscle becomes weak, the antagonist will overpower it and cause progressive deformity. The focus of the early minimally invasive approach is to decrease the forces that cause progressive deformity yet maintain function, where possible. Our goal has been to maintain a functional and braceable foot and ankle, with the hope of avoiding or limiting the extent of future major reconstructive surgery. The presented cases highlight the patient selection criteria, the ideal timing of early surgical intervention, the procedure selection criteria, and operative pearls. The early minimally invasive approach includes plantar fasciotomy, Achilles tendon lengthening, transfer of the peroneus longus to the fifth metatarsal, Hibbs and Jones tendon transfer, and hammertoe repair of digits 1 to 5. PMID- 25131390 TI - Long-term functional outcomes and quality of life after oncologic surgery and microvascular reconstruction in patients with oral or oropharyngeal cancer. AB - CONCLUSIONS: Surgery for oral or oropharyngeal cancer with free-flap reconstruction is associated with moderate but persistent functional and quality of life (QoL) problems. Patient age, tumor stage, tumor site, and radiotherapy were the main predictors of functional outcome. OBJECTIVES: To evaluate long-term functional outcomes and QoL, and to determine their predictive factors in patients with oral or oropharyngeal cancer after oncologic surgery and free-flap reconstruction. METHODS: Patients who underwent surgery with free-flap reconstruction for oral or oropharyngeal cancer between 2000 and 2009 who were alive at least 1 year after therapy were included in this study. Patients completed the Voice Handicap Index (VHI-10) questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaires QLQ C30 and H&N35. Swallowing was evaluated using the Dysphagia Outcome and Severity Scale (DOSS) and by flexible fiberoptic laryngoscopy. RESULTS: Sixty-four patients were included in the study. VHI-10 mean score was 11.2 +/- 9 and its predictive factors were T stage (p = 0.005) and tumor involvement of the tongue base (p = 0.01). The mean DOSS score was 4 +/- 0.8. Age (p = 0.008), gender (p = 0.04), and radiotherapy (p = 0.001) were the main predictive factors of the DOSS score. PMID- 25131391 TI - Gastroesophageal reflux and carcinoma of larynx or pharynx: a meta-analysis. AB - CONCLUSION: The meta-analysis supported the proposition that the prevalence of gastroesophageal reflux disease (GERD) was associated with laryngeal cancer, particularly in the hospital-based control group and diagnosed by esophagogastroduodenoscopy (EGD) or esophageal pH monitoring. However, no significant association was found between GERD and pharyngeal carcinoma. OBJECTIVES: A number of studies have been conducted to investigate the relationship between gastroesophageal reflux and laryngeal or pharyngeal carcinoma. The conclusions are still debated. METHODS: We conducted a systematic review of studies associated with the prevalence of GERD in laryngeal or pharyngeal cancer, published up to November 2013.Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random effects models or fixed effects models, according to heterogeneity I(2). RESULTS: Ten studies were included in this meta-analysis. On average, GERD was significantly higher in the tumor tissue of the study group compared with normal tissue of the control group (OR = 2.17, 95% CI = 1.50, 3.14; random effects analysis). The pooled ORs for laryngeal carcinoma were 2.21 (95% CI = 1.53-3.19; I(2) = 97, random effects model) and 3.76 (95% CI = 0.21-67.48; I(2) = 94, random effects model) for pharyngeal carcinoma. PMID- 25131392 TI - Factors associated with malnutrition in patients with head and neck cancer. AB - CONCLUSIONS: Comorbidities as well as T classification were the primary determinants for the nutritional status of patients with head and neck cancer. OBJECTIVES: We aimed to elucidate the underlying conditions of malnutrition in patients with head and neck cancer. METHODS: We retrospectively reviewed 726 patients diagnosed with head and neck cancer between 2004 and 2013. Associations between malnutrition and clinical parameters were assessed using univariate and multivariate analyses. RESULTS: Median body mass index was 21.5 (range 11.6 38.0). According to World Health Organization criteria, the nutritional status of these patients was classified into four groups: underweight (18%), normal (63%), overweight (17%), and obese (1%). Comorbidities were detected in 40% of patients. Multivariate analysis revealed the following factors to be independent factors associated with malnutrition: advanced T stage, metachronous cancer, collagen disease, gastrointestinal disease, and pulmonary disease. PMID- 25131393 TI - Long-term administration of vasopressin can cause Meniere's disease in mice. AB - CONCLUSION: A new murine model of Meniere's disease has been developed, based on long-term administration of vasopressin. Induction of vestibular dysfunction in the present animal model can cause additional stress, by reducing inner ear blood flow. Latanoprost, a selective agonist for the FP prostanoid receptor, may become a new remedy for Meniere's disease. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, with a closer resemblance to the pathophysiological process in Meniere's disease. METHODS: Adult CBA/J or ICR mice were treated by subcutaneous injection of vasopressin for 5 days up to 8 weeks. Morphological analyses were performed of the cochlea, vestibular end organs and endolymphatic sac. The effect of latanoprost on the development of endolymphatic hydrops was also examined. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops, increasing in severity as the vasopressin treatment was prolonged. Animals treated with vasopressin for 8 weeks showed severe endolymphatic hydrops with partial loss of outer hair cells and spiral ganglion cells. These animals also had a reversible vestibular dysfunction following intratympanic injection of epinephrine. Latanoprost inhibited the development of endolymphatic hydrops caused by vasopressin. PMID- 25131396 TI - Assessing carbon and hydrogen isotopic fractionation of diesel fuel n-alkanes during progressive evaporation. AB - Compound-specific isotope analysis offers potential for fingerprinting of diesel fuels, however, possible confounding effects of isotopic fractionation due to evaporation need to be assessed. This study measured the fractionation of the stable carbon and hydrogen isotopes in n-alkane compounds in neat diesel fuel during evaporation. Isotope ratios were measured using a continuous flow gas chromatograph/isotope ratio mass spectrometer. Diesel samples were progressively evaporated at 24 +/- 2 degrees C for 21 days. Increasing depletion of deuterium in nC12-nC17 alkanes in the remaining liquid with increasing carbon chain length was observed. Negligible carbon isotope fractionation was observed. Preferential vaporization was measured for the shorter chain n-alkanes and the trend decreased with increasing chain length. The decrease in delta(2) H values indicates the preferential vaporization of the isotopically heavier species consistent with available quantitative data for hydrocarbons. These results are most important in the application of stable isotope technology to forensic analysis of diesel. PMID- 25131395 TI - Vasorelaxant effects of 1-nitro-2-phenylethene in rat isolated aortic rings. AB - Previously, we showed that nitro-2-phenylethane is a vasorelaxant constituent of the essential oil of Aniba canelilla. Here, we investigated the mechanisms underlying the vascular effects of 1-nitro-2-phenylethene (NPe), a structural analog of 1-nitro-2-phenylethane obtained synthetically, in rat isolated thoracic aortic preparations. At 0.1-100 MUg/mL, NPe similarly relaxed endothelium-intact or endothelium-denuded aortic preparations pre-contracted with 60mM KCl or with phenylephrine (PHE, 1 MUM). Vasorelaxant effects of NPe against PHE-induced contractions remained unaffected following blockade of potassium channels by TEA, and inhibition of either nitric oxide synthase by l-NAME, cyclooxygenase by indomethacin or guanylate cyclase by ODQ. In preparations maintained under Ca(2+) free conditions, NPe significantly reduced the contractions induced (i) by PHE, but not those evoked by caffeine, (ii) by CaCl2 in either PHE (in the presence of 1 MUM verapamil)- or KCl-stimulated preparations, (iii) by extracellular Ca(2+) restoration in thapsigargin-treated aortic preparations, and (iv) by the activator of protein kinase C phorbol-12,13-dibutyrate or the inhibitor of protein tyrosine phosphatase sodium orthovanadate. It is concluded that NPe induced an endothelium-independent vasorelaxation with potency greater than its structural analog 1-nitro-2-phenylethane. Such action appears to occur intracellularly probably through inhibition of contractile events that are clearly independent of Ca(2+) influx from the extracellular milieu. PMID- 25131394 TI - Heterozygous FGF8 mutations in patients presenting cryptorchidism and multiple VATER/VACTERL features without limb anomalies. AB - BACKGROUND: The acronym VATER/VACTERL association describes the combination of at least three of the following cardinal features: vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. Although fibroblast growth factor-8 (FGF8) mutations have mainly found in patients with Kallmann syndrome, mice with a hypomorphic Fgf8 allele or complete gene invalidation display, aside from gonadotropin-releasing hormone deficiency, parts or even the entire spectrum of human VATER/VACTERL association. METHODS: We performed FGF8 gene analysis in 49 patients with VATER/VACTERL association and 27 patients presenting with a VATER/VACTERL-like phenotype (two cardinal features). RESULTS: We identified two heterozygous FGF8 mutations in patients displaying either VATER/VACTERL association (p.Gly29_Arg34dup) or a VATER/VACTERL-like phenotype (p.Pro26Leu) without limb anomalies. Whereas the duplication mutation has not been reported before, p.Pro26Leu was once observed in a Kallmann syndrome patient. Both our patients had additional bilateral cryptorchidism, a key phenotypic feature in males with FGF8 associated Kallmann syndrome. Each mutation was paternally inherited. Besides delayed puberty in both and additional unilateral cryptorchidism in one of the fathers, they were otherwise healthy. Serum hormone levels downstream the gonadotropin-releasing hormone in both patients and their fathers were within normal range. CONCLUSION: Our results suggest FGF8 mutations to contribute to the formation of the VATER/VACTERL association. Further studies are needed to support this observation. PMID- 25131398 TI - Teen parties: who has parties, what predicts whether there is alcohol and who supplies the alcohol? AB - This study explores which youth are more likely to have parties at home, what factors are associated with the presence of alcohol at parties, and who supplies the alcohol. We collected data in 2011 and 2012 through telephone interviews with 1,121 teens living in 50 mid-sized California cities. Overall, about a quarter of teens reported having had a party at their house in the past 12 months, of whom 39 % reported that there was alcohol at their last party. Multiple sources supplied alcohol for most parties. Seventy-two percent of those having a party stated that at least one of their parents knew about their last party, and 64 % reported that a parent was home at least part of the time. Seventy percent of youth who hosted a party with alcohol said that their parent(s) definitely knew that there was alcohol at the party, 24 % replied that their parent(s) probably knew, and only 5 % said that their parent(s) did not know that there was alcohol at the party. Logistic regression analyses indicated that youth with parents who host parties at home are themselves more likely to host parties at home. Having alcohol at a party was positively related to the age of the teen and the number of guests attending, and was negatively related to parents' awareness of the party. However, we found no relationship between whether a parent was at home at the time of the party and whether it included alcohol. These findings suggest that teens who have parties with alcohol at home have parents who know that there is alcohol at the party, even though only a small number of parents provided alcohol for the party. PMID- 25131397 TI - Understanding the determinants of substrate specificity in IMP family metallo beta-lactamases: the importance of residue 262. AB - In Gram-negative bacteria, resistance to beta-lactam antibacterials is largely due to beta-lactamases and is a growing public health threat. One of the most concerning beta-lactamases to evolve in bacteria are the Class B enzymes, the metallo-beta-lactamases (MBLs). To date, penams and cephems resistant to hydrolysis by MBLs have not yet been found. As a result of this broad substrate specificity, a better understanding of the role of catalytically important amino acids in MBLs is necessary to design novel beta-lactams and inhibitors. Two MBLs, the wild type IMP-1 with serine at position 262, and an engineered variant with valine at the same position (IMP-1-S262V), were previously found to exhibit very different substrate spectra. These findings compelled us to investigate the impact of a threonine at position 262 (IMP-1-S262T) on the substrate spectrum. Here, we explore MBL sequence-structure-activity relationships by predicting and experimentally validating the effect of the S262T substitution in IMP-1. Using site-directed mutagenesis, threonine was introduced at position 262, and the IMP 1-S262T enzyme, as well as the other two enzymes IMP-1 and IMP-1-S262V, were purified and kinetic constants were determined against a range of beta-lactam antibacterials. Catalytic efficiencies (kcat /KM ) obtained with IMP-1-S262T and minimum inhibitory concentrations (MICs) observed with bacterial cells expressing the protein were intermediate or comparable to the corresponding values with IMP 1 and IMP-1-S262V, validating the role of this residue in catalysis. Our results reveal the important role of IMP residue 262 in beta-lactam turnover and support this approach to predict activities of certain novel MBL variants. PMID- 25131399 TI - Morphogenesis of Streptomyces in submerged cultures. AB - Members of the genus Streptomyces are mycelial bacteria that undergo a complex multicellular life cycle and propagate via sporulation. Streptomycetes are important industrial microorganisms, as they produce a plethora of medically relevant natural products, including the majority of clinically important antibiotics, as well as a wide range of enzymes with industrial application. While development of Streptomyces in surface-grown cultures is well studied, relatively little is known of the parameters that determine morphogenesis in submerged cultures. Here, growth is characterized by the formation of mycelial networks and pellets. From the perspective of industrial fermentations, such mycelial growth is unattractive, as it is associated with slow growth, heterogeneous cultures, and high viscosity. Here, we review the current insights into the genetic and environmental factors that determine mycelial growth and morphology in liquid-grown cultures. The genetic factors include cell-matrix proteins and extracellular polymers, morphoproteins with specific roles in liquid culture morphogenesis, with the SsgA-like proteins as well-studied examples, and programmed cell death. Environmental factors refer in particular to those dictated by process engineering, such as growth media and reactor set-up. These insights are then integrated to provide perspectives as to how this knowledge can be applied to improve streptomycetes for industrial applications. PMID- 25131400 TI - Interactions between arbuscular mycorrhizal fungi and organic material substrates. AB - Arbuscular mycorrhizal (AM) associations are widespread and form between ca. two thirds of all land plants and fungi in the phylum Glomeromycota. The association is a mutualistic symbiosis with the fungi enhancing nutrient capture for the plant while obtaining carbon in return. Although arbuscular mycorrhizal fungi (AMF) lack any substantial saprophytic capability they do preferentially associate with various organic substrates and respond by hyphal proliferation, indicating the fungus derives a benefit from the organic substrate. AMF may also enhance decomposition of the organic material. The benefit to the host plant of this hyphal proliferation is not always apparent, particularly regarding nitrogen (N) transfer, and there may be circumstances under which both symbionts compete for the N released given both have a large demand for N. The results of various studies examining AMF responses to organic substrates and the interactions with other members of the soil community will be discussed. PMID- 25131401 TI - Transcription regulation in the third domain. AB - The ability of organisms to sense and respond to their environment is essential to their survival. This is no different for members of the third domain of life, the Archaea. Archaea are found in diverse and often extreme habitats. However, their ability to sense and respond to their environment at the level of gene expression has been understudied when compared to bacteria and eukaryotes. Over the last decade, the field has expanded, and a variety of unique and interesting regulatory schemes have been unraveled. In this review, the current state of knowledge of archaeal transcription regulation is explored. PMID- 25131402 TI - Bacteria-phage interactions in natural environments. AB - Phages are considered the most abundant and diverse biological entities on Earth and are notable not only for their sheer abundance, but also for their influence on bacterial hosts. In nature, bacteria-phage relationships are complex and have far-reaching consequences beyond particular pairwise interactions, influencing everything from bacterial virulence to eukaryotic fitness to the carbon cycle. In this review, we examine bacteria and phage distributions in nature first by highlighting biogeographic patterns and nonhost environmental influences on phage distribution, then by considering the ways in which phages and bacteria interact, emphasizing phage life cycles, bacterial responses to phage infection, and the complex patterns of phage host specificity. Finally, we discuss phage impacts on bacterial abundance, genetics, and physiology, and further aim to clarify distinctions between current theoretical models and point out areas in need of future research. PMID- 25131403 TI - The interactions of bacteria with fungi in soil: emerging concepts. AB - In this chapter, we review the existing literature on bacterial-fungal interactions in soil, exploring the role fungi may play for soil bacteria as providers of hospitable niches. A focus is placed on the mycosphere, i.e., the narrow zone of influence of fungal hyphae on the external soil milieu, in which hypha-associated bacterial cells dwell. Evidence is brought forward for the contention that the hyphae of both mycorrhizal and saprotrophic fungi serve as providers of ecological opportunities in a grossly carbon-limited soil, as a result of their release of carbonaceous compounds next to the provision of a colonizable surface. Soil bacteria of particular nature are postulated to have adapted to such selection pressures, evolving to the extent that they acquired capabilities that allow them to thrive in the novel habitat created by the emerging fungal hyphae. The mechanisms involved in the interactions and the modes of genetic adaptation of the mycosphere dwellers are discussed, with an emphasis on one key mycosphere-adapted bacterium, Burkholderia terrae BS001. In this discussion, we interrogate the positive interactions between soil fungi and bacteria, and refrain from considering negative interactions. PMID- 25131404 TI - Production of specialized metabolites by Streptomyces coelicolor A3(2). AB - The actinomycetes are well-known bioactive natural product producers, comprising the Streptomycetes, the richest drug-prolific family in all kingdoms, producing therapeutic compounds for the areas of infection, cancer, circulation, and immunity. Completion and annotation of many actinomycete genomes has highlighted further how proficient these bacteria are in specialized metabolism, which have been largely underexploited in traditional screening programs. The genome sequence of the model strain Streptomyces coelicolor A3(2), and subsequent development of genomics-driven approaches to understand its large specialized metabolome, has been key in unlocking the high potential of specialized metabolites for natural product genomics-based drug discovery. This review discusses systematically the biochemistry and genetics of each of the specialized metabolites of S. coelicolor and describes metabolite transport processes for excretion and complex regulatory patterns controlling biosynthesis. PMID- 25131405 TI - Synthetic polyester-hydrolyzing enzymes from thermophilic actinomycetes. AB - Thermophilic actinomycetes produce enzymes capable of hydrolyzing synthetic polyesters such as polyethylene terephthalate (PET). In addition to carboxylesterases, which have hydrolytic activity predominantly against PET oligomers, esterases related to cutinases also hydrolyze synthetic polymers. The production of these enzymes by actinomycetes as well as their recombinant expression in heterologous hosts is described and their catalytic activity against polyester substrates is compared. Assays to analyze the enzymatic hydrolysis of synthetic polyesters are evaluated, and a kinetic model describing the enzymatic heterogeneous hydrolysis process is discussed. Structure-function and structure-stability relationships of actinomycete polyester hydrolases are compared based on molecular dynamics simulations and recently solved protein structures. In addition, recent progress in enhancing their activity and thermal stability by random or site-directed mutagenesis is presented. PMID- 25131406 TI - Characterization of robotic system passive path repeatability during specimen removal and reinstallation for in vitro knee joint testing. AB - Robotic testing systems are commonly utilized for the study of orthopaedic biomechanics. Quantification of system error is essential for reliable use of robotic systems. Therefore, the purpose of this study was to quantify a 6-DOF robotic system's repeatability during knee biomechanical testing and characterize the error induced in passive path repeatability by removing and reinstalling the knee. We hypothesized removing and reinstalling the knee would substantially alter passive path repeatability. Testing was performed on four fresh-frozen cadaver knees. To determine repeatability and reproducibility, the passive path was collected three times per knee following the initial setup (intra-setup), and a single time following two subsequent re-setups (inter-setup). Repeatability was calculated as root mean square error. The intra-setup passive path had a position repeatability of 0.23 mm. In contrast, inter-setup passive paths had a position repeatability of 0.89 mm. When a previously collected passive path was replayed following re-setup of the knee, resultant total force repeatability across the passive path increased to 28.2N (6.4N medial-lateral, 25.4N proximal-distal, and 10.5 N anterior-posterior). This study demonstrated that removal and re-setup of a knee can have substantial, clinically significant changes on our system's repeatability and ultimately, accuracy of the reported results. PMID- 25131407 TI - Suppression of NGB and NAB/ERabp1 in tomato modifies root responses to potato cyst nematode infestation. AB - Plant-parasitic nematodes cause significant damage to major crops throughout the world. The small number of genes conferring natural plant resistance and the limitations of chemical control require the development of new protective strategies. RNA interference or the inducible over-expression of nematicidal genes provides an environment-friendly approach to this problem. Candidate genes include NGB, which encodes a small GTP-binding protein, and NAB/ERabp1, which encodes an auxin-binding protein, which were identified as being up-regulated in tomato roots in a transcriptome screen of potato cyst nematode (Globodera rostochiensis) feeding sites. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization confirmed the localized up-regulation of these genes in syncytia and surrounding cells following nematode infection. Gene-silencing constructs were introduced into tomato, resulting in a 20%-98% decrease in transcription levels. Nematode infection tests conducted on transgenic plants showed 57%-82% reduction in the number of G. rostochiensis females in vitro and 30%-46% reduction in pot trials. Transmission electron microscopy revealed a deterioration of cytoplasm, and degraded mitochondria and plastids, in syncytia induced in plants with reduced NAB/ERabp1 expression. Cytoplasm in syncytia induced in plants with low NGB expression was strongly electron translucent and contained very few ribosomes; however, mitochondria and plastids remained intact. Functional impairments in syncytial cytoplasm of silenced plants may result from NGB's role in ribosome biogenesis; this was confirmed by localization of yellow fluorescent protein (YFP)-labelled NGB protein in nucleoli and co-repression of NGB in plants with reduced NAB/ERabp1 expression. These results demonstrate that NGB and NAB/ERabp1 play important roles in the development of nematode-induced syncytia. PMID- 25131408 TI - Exit strategy for unmappable VT? PMID- 25131410 TI - Low capping group surface density on zinc oxide nanocrystals. AB - The ligand shell of colloidal nanocrystals can dramatically affect their stability and reaction chemistry. We present a methodology to quantify the dodecylamine (DDA) capping shell of colloidal zinc oxide nanocrystals in a nonpolar solvent. Using NMR spectroscopy, three different binding regimes are observed: strongly bound, weakly associated, and free in solution. The surface density of bound DDA is constant over a range of nanocrystal sizes, and is low compared to both predictions of the number of surface cations and maximum coverages of self-assembled monolayers. The density of strongly bound DDA ligands on the as-prepared ZnO NCs is 25% of the most conservative estimate of the maximum surface DDA density. Thus, these NCs do not resemble the common picture of a densely capped surface ligand layer. Annealing the ZnO NCs in molten DDA for 12 h at 160 degrees C, which is thought to remove surface hydroxide groups, resulted in a decrease of the weakly associated DDA and an increase in the density of strongly bound DDA, to ca. 80% of the estimated density of a self assembled monolayer on a flat ZnO surface. These findings suggest that as prepared nanocrystal surfaces contain hydroxide groups (protons on the ZnO surfaces) that inhibit strong binding of DDA. PMID- 25131409 TI - The effect of obesity and type 1 diabetes on renal function in children and adolescents. AB - BACKGROUND: Early signs of renal complications can be common in youths with type 1 diabetes (T1D). Recently, there has been an increasing interest in potential renal complications associated with obesity, paralleling the epidemics of this condition, although there are limited data in children. HYPOTHESIS: Obese children and adolescents present signs of early alterations in renal function similar to non-obese peers with T1D. SUBJECTS: Eighty-three obese (age: 11.6 +/- 3.0 yr), 164 non-obese T1D (age: 12.4 +/- 3.2 yr), and 71 non-obese control (age: 12.3 +/- 3.2 yr) children and adolescents were enrolled in the study. METHODS: Anthropometric parameters and blood pressure were measured. Renal function was assessed by albumin excretion rate (AER), serum cystatin C, creatinine and estimated glomerular filtration rate (e-GFR), calculated using the Bouvet's formula. RESULTS: Obese and non-obese T1D youths had similar AER [8.9(5.9-10.8) vs. 8.7(5.9-13.1) ug/min] and e-GFR levels (114.8 +/- 19.6 vs. 113.4 +/- 19.1 mL/min), which were higher than in controls [AER: 8.1(5.9-8.7) ug/min, e-GFR: 104.7 +/- 18.9 mL/min]. Prevalence of microalbuminuria and hyperfiltration was similar between obese and T1D youths and higher than their control peers (6.0 vs. 8.0 vs. 0%, p = 0.02; 15.9 vs. 15.9 vs. 4.3%, p = 0.03, respectively). Body mass index (BMI) z-score was independently related to e-GFR (r = 0.328; p < 0.001), and AER (r = 0.138; p = 0.017). Hemoglobin A1c (HbA1c) correlated with AER (r = 0.148; p = 0.007) but not with eGFR (r = 0.041; p = 0.310). CONCLUSIONS: Obese children and adolescents show early alterations in renal function, compared to normal weight peers, and they have similar renal profiles than age-matched peers with T1D. PMID- 25131411 TI - Defining the biology component of the drug discovery strategy for malaria eradication. AB - Malaria is still considered a deadly scourge in Africa, Asia, and South America despite improved vector control and curative treatments with new antimalarial combinations. The next challenge is to work towards disease eradication. To achieve this goal it is crucial to develop, validate, and integrate biological assays into test cascades that align with the key target product profiles. For anti-relapse, a parent molecule should kill hypnozoites or cause activation of Plasmodium vivax liver stages. For transmission blocking, dual equal-activity antimalarials killing both the asexual and the sexual parasite stages in human blood are favored. Finally, by assessing cross resistance and generating drug resistance in the laboratory, it is expected that new medicines with acceptable resistance profiles will be forthcoming. PMID- 25131412 TI - Lesions to the CA2 region of the hippocampus impair social memory in mice. AB - The function of the CA2 region of the hippocampus is poorly understood. Although the CA1 and CA3 regions have been extensively studied, for years the CA2 region has primarily been viewed as a linking area between the two. However, the CA2 region is known to have distinct neurochemical and structural features that are different from the other parts of the hippocampus and in recent years it has been suggested that the CA2 region may play a role in the formation and/or recall of olfactory-based memories needed for normal social behavior. Although this hypothesis has been supported by hippocampal lesion studies that have included the CA2 region, no studies have attempted to specifically lesion the CA2 region of the hippocampus in mice to determine the effects on social recognition memory and olfaction. To fill this knowledge gap, we sought to perform excitotoxic N methyl-D-aspartate lesions of the CA2 region and determine the effects on social recognition memory. We predicted that lesions of the CA2 region would impair social recognition memory. We then went on to test olfaction in CA2-lesioned mice, as social memory requires a functional olfactory system. Consistent with our prediction, we found that CA2-lesioned animals had impaired social recognition. These findings are significant because they confirmed that the CA2 region of the hippocampus is a part of the neural circuitry that regulates social recognition memory, which may have implications for our understanding of the neural regulation of social behavior across species. PMID- 25131413 TI - Pilot study of an oral care protocol on poststroke survivors. AB - PURPOSE: The pilot study purpose was to determine the effects of a new standardized oral care protocol (intervention) to usual care practices (control) in poststroke patients. DESIGN: This study is a randomized controlled clinical trial. METHOD: Fifty-one subjects were enrolled. Subjects in the intervention group received oral care twice a day including tooth brushing, tongue brushing, flossing, mouth rinse, and lip care while control patients received usual oral care. FINDINGS: Subjects in the control and intervention groups showed improvement in their oral health assessments, swallowing abilities and oral intake. There were no significant differences between the two groups. Although not statistically significant, overall prevalence of methicillin-resistant Staphylococcus aureus and methicillin-sensitive Staphylococcus aureus colonization in the control group almost doubled (from 4.8% to 9.5%), while colonization in the intervention group decreased (from 20.8% to 16.7%). CONCLUSIONS/CLINICAL RELEVANCE: These findings demonstrate the importance of oral care in the poststroke patient with dysphagia. PMID- 25131414 TI - Comparison of conventional freezing and vitrification with dimethylformamide and ethylene glycol for cryopreservation of ovine embryos. AB - The aim of this work was to evaluate the efficiency of the cryoprotectants dimethylformamide and ethylene glycol for cryopreservation of ovine embryos using vitrification and conventional freezing. The recovered embryos were distributed randomly in three treatment groups: Gr. 1: conventional freezing (n = 44), Gr. 2: vitrification with ethylene glycol (n = 39) and Gr. 3: vitrification with dimethylformamide (n = 38). Quality of fresh embryos in control group as well as of frozen and vitrified embryos was examined by three methodologies: staining with propidium iodide and Hoechst 33258 and evaluation under fluorescent microscopy, evaluation of re-expansion and hatching rates after culture, and determination of apoptotic index with TUNEL technique. It was established that re expansion rate in all treatment groups was similar. In the same time, hatching rates were higher in Gr. 1 (40.5%) and Gr. 2 (35.3%) in comparison with Gr. 3 (15.5%, p < 0.05). The number of dead cells in vitrified embryos of Gr. 2 and Gr. 3 was higher (42.6 +/- 26.2 and 63.2 +/- 34.65, respectively) in comparison with Gr. 1 (conventional freezing, 10.1 +/- 8.5, p < 0.05). Embryos vitrified with dimethylformamide included the same quality of apoptotic cells that Gr. 1 (conventional freezing) and fresh embryos. In conclusion, the dimethylformamide and ethylene glycol used as cryoprotectant to vitrify ovine embryos, in the concentrations and exposition time tested in this work, were not as efficient as the conventional freezing for cryopreservation of ovine embryos Thus, the conventional freezing with ethylene glycol was the most efficient method to cryopreserve ovine embryos in comparison with vitrification. PMID- 25131415 TI - Pneumocystis jirovecii pneumonia in patients with end-stage renal disease: a comparison with the general population. AB - BACKGROUND: Data on occurrence and risk factors for pneumocystis pneumonia (PCP) in patients with end-stage renal disease (ESRD) are sparse. METHODS: This was a nationwide population-based study assessing occurrence and risk factors for PCP among patients with ESRD and population controls over a 21-year period (1/1 1990 to 31/12 2010). Using Danish registry data, first-time diagnoses of PCP were identified. RESULTS: We identified 13 296 adult patients with ESRD and 244 255 controls, yielding 63 560 and 2 223 660 person-years of follow-up (PYFU), respectively. Fifty-eight first-time diagnoses of PCP were recorded in the ESRD group. Forty-six episodes occurred among renal transplant recipients (RTx) and 12 among haemodialysis patients (HD), yielding incidence rates of 181 (136-242) and 43.1 (24.5-75.9) per 100 000 PYFU. Compared to population controls, we found incidence rate-ratios of 125.9 (78.4-204) among RTx and 29.9 (14.1-59.7) among HD patients. Risk factors for PCP in RTx were age 50-65 years, age > 65 years, diabetes, polycystic kidney disease and hypertensive kidney disease/nephrosclerosis with an IRR of 2.22 (1.14-4.31), 3.12 (1.35-7.21), 3.44 (1.16-10.2), 4.25 (1.55-11.7) and 3.87 (1.49-10.0), respectively, and more than 36 months of dialysis before transplantation with an IRR of 1.99 (1.03-3.84). Among RTx the risk of PCP was highest during the first 6 months post transplantation and increased from the beginning (IR1990-94 = 111 (46.3-267) per 100 000 PYFU) towards the end of the study period (IR2005-10 = 299 (203-439)). CONCLUSION: The PCP risk is substantial in RTx within the first 6 months of transplantation, emphasizing the potential benefit of prophylactic treatment in the early post-transplant period. Importantly, we identified subgroups within the RTx group that require more attention. PMID- 25131416 TI - Interface-induced nonswitchable domains in ferroelectric thin films. AB - Engineering domains in ferroelectric thin films is crucial for realizing technological applications including non-volatile data storage and solar energy harvesting. Size and shape of domains strongly depend on the electrical and mechanical boundary conditions. Here we report the origin of nonswitchable polarization under external bias that leads to energetically unfavourable head-to head domain walls in as-grown epitaxial PbZr(0.2)Ti(0.8)O3 thin films. By mapping electrostatic potentials and electric fields using off-axis electron holography and electron-beam-induced current with in situ electrical biasing in a transmission electron microscope, we show that electronic band bending across film/substrate interfaces locks local polarization direction and further produces unidirectional biasing fields, inducing nonswitchable domains near the interface. Presence of oxygen vacancies near the film surface, as revealed by electron energy loss spectroscopy, stabilizes the charged domain walls. The formation of charged domain walls and nonswitchable domains reported in this study can be an origin for imprint and retention loss in ferroelectric thin films. PMID- 25131417 TI - Cover versus recovery: contrasting responses of two indicators in seagrass beds. AB - Despite being a highly valuable key-stone ecosystem, seagrass meadows are threatened and declining worldwide, creating urgent need for indicators of their health status. We compared two indicators for seagrass health: standing leaf area index versus relative recovery from local disturbance. Disturbance was created by removing aboveground biomass and recording the rate of regrowth for Zostera marina meadows exposed to contrasting wave regimes and nutrient stress levels. Within the experimental period, relative regrowth in gaps was around 50% in most plots, except for the ambient nutrient treatment at the sheltered site, where it exceeded 100%. The two indicators showed an opposite response to disturbance: the higher the standing leaf area index, the lower the relative recovery from disturbance. This conflicting response raises the question on the proper interpretation of such indicators to estimate seagrass health and resilience, and how to ideally monitor seagrass ecosystems in order to predict collapse. PMID- 25131418 TI - Marine debris is selected as nesting material by the brown booby (Sula leucogaster) within the Swain Reefs, Great Barrier Reef, Australia. AB - Many seabirds are impacted by marine debris through its presence in foraging and nesting areas. To determine the extent of this problem, marine debris use in nest material of the brown booby (Sula leucogaster) in the Great Barrier Reef, Australia, was investigated. Nine cays were examined using beach and nest surveys. On average, four marine debris items were found per nest (n=96) with 58.3% of surveyed nests containing marine debris. The source of marine debris in nests and transects were primarily oceanic. Hard plastic items dominated both nest (56.8%) and surveyed beaches (72.8%), however only two item types were significantly correlated between these surveys. Nest surveys indicated higher levels of black and green items compared to beach transects. This selectivity for colours and items suggest these nests are not good indicators of environmental loads. This is the first study to examine S. leucogaster nests for marine debris in this location. PMID- 25131419 TI - Vertical distribution and source identification of polycyclic aromatic hydrocarbons (PAHs) in southwest of the Caspian Sea: most petrogenic events during the late Little Ice Age. AB - In this study, 75 samples of two (210)Pb-dated cores from the southwest of the Caspian Sea were analysed for 30 compounds of polycyclic aromatic hydrocarbons (PAHs). The TPAH29 flux of the last six centuries ranged from 16.3 to 177.3 and 22.3 to 426.2 ng cm(-2)y(-1) in the Rezvanshahr and Anzali core sediments, respectively. Prior to 1840, four distinct maxima in PAH fluxes (61-426.2 ng cm( 2)y(-1)) with a low weathered petrogenic pattern were found in each of the core sediments. Simultaneity of distinct peaks of PAH fluxes before 1840 and Caspian Sea level high-stands during the Little Ice Age (LIA), revealed the high importance of this phenomenon in washing and transport of land-based oil pollution into the Caspian Sea. An overall increase in some diagnostic ratios (Flu/202, IP/276 and BaA/228), especially after 1940, indicated increase of pyrogenic PAHs as a result of industrial development in the catchment area. PMID- 25131420 TI - Sources and preservation of sedimentary organic matter in the Southern Bohai Sea and the Yellow Sea: evidence from lipid biomarkers. AB - The region of Southern Bohai Sea (SBS) and Yellow Sea (YS) represents one of the best examples of large river-dominated ocean margins. The transport and accumulation of sediments played a primary role in distribution of the lipids in the region and could lead to a preferential accumulation of these more refractory land-based lipids. The spatial distribution of total organic carbon (TOC) matched with the lipid distributions over the shelf, and high TOC presented in the central YS, but TOC burial fluxes decreased from 110 ton/km(2)/yr of SBS to 25-32 ton/km(2)/yr of YS. Good correlations were observed between terrestrial n-alkanes and TOC in the sediments of SBS and northern YS, but they were poor for southern YS, meanwhile higher ratios of nC27+nC29+nC31/nC15+nC17+nC19 (12+/-6) were observed in SBS, and lower in YS (2.2+/-1.0), suggesting the Yellow River discharge was an important source of terrestrial organic matter to the shelf. PMID- 25131422 TI - Writing and functionalisation of suspended DNA nanowires on superhydrophobic pillar arrays. AB - Nanowire arrays and networks with precisely controlled patterns are very interesting for innovative device concepts in mesoscopic physics. In particular, DNA templates have proven to be versatile for the fabrication of complex structures that obtained functionality via combinations with other materials, for example by functionalisation with molecules or nanoparticles, or by coating with metals. Here, the controlled motion of the a three-phase contact line (TCL) of DNA-loaded drops on superhydrophobic substrates is used to fabricate suspended nanowire arrays. In particular, the deposition of DNA wires is imaged in situ, and different patterns are obtained on hexagonal pillar arrays by controlling the TCL velocity and direction. Robust conductive wires and networks are achieved by coating the wires with a thin layer of gold, and as proof of concept conductivity measurements are performed on single suspended wires. The plastic material of the superhydrophobic pillars ensures electrical isolation from the substrate. The more general versatility of these suspended nanowire networks as functional templates is outlined by fabricating hybrid organic-metal-semiconductor nanowires by growing ZnO nanocrystals onto the metal-coated nanowires. PMID- 25131423 TI - Mycobacterium tuberculosis Secreted Proteins As Potential Biomarkers for the Diagnosis of Active Tuberculosis and Latent Tuberculosis Infection. AB - BACKGROUND: The detection of Mycobacterium tuberculosis (Mtb) specific human antibodies has been an important diagnostic aid in the diagnosis of tuberculosis (TB) cases with smear-negative sputum samples, especially for the screening of high-risk population. This study focused on the analysis and comparison of the four potential Mtb-secreted proteins (ESAT6, CFP10, Ag85B, Hsp16.3) and the fusion protein Ag85B-Hsp16.3 as new markers in the serodiagnosis between active TB and latent TB infection (LTBI). METHODS: These five recombinant proteins were produced and used in optimized ELISA to detect IgG serum antibodies against the four secreted proteins. The capacity of identifying infection was evaluated either in active TB patients or LTBI individuals, which was compared with the control groups consisting of hospitalized non-TB individuals. RESULTS: The results showed that Ag85B-Hsp16.3/ESAT6 and Hsp16.3/ESAT6 were the best associated antigens for serology diagnosis of the active TB and LTBI individuals because of their specificity, sensitivity, YI values, and positive rates, respectively. ELISA test demonstrated that 41.67% (25/60) of blood donors respond to Ag85B-Hsp16.3/ESAT6. The consistency of this positive respond with clinical diagnosis almost reached 84% (21/25). CONCLUSION: Thus, a combined test of multiple Mtb-secreted proteins Ag85B, Hsp16.3, and ESAT6 may be the ascendant preliminary screening antigens for active TB or LTBI patients. PMID- 25131424 TI - Current update of chemomechanical caries removal methods. AB - Chemomechanical caries removal is an excellent method for minimally invasive caries excavation, and the removal agents are either sodium hypochlorite (NaOCl)- or enzyme-based. The NaOCl-based agents include GK-101, GK-101E (Caridex) and Carisolv, and the enzyme-based agents include Papacarie and the experimental material, Biosolv. This review outlines the changes in chemomechanical caries removal methods and focuses on recently published laboratory and clinical studies. The historical development, mechanism of action, excavation time and biological effects on pulp and dental hard tissues are described. Based on existing evidence, the currently available chemomechanical caries removal methods are viable alternatives to conventional rotary instrument methods. Chemomechanical methods could be extremely useful in very anxious, disabled and paediatric patients. It does seem some of these agents would still benefit from quicker excavation times in order to achieve more universal acceptance. However, as a means of conserving the caries-affected dentine, chemomechanical caries removal is possibly much more successful than conventional rotary instrumentation. PMID- 25131421 TI - Single-cell genetic analysis reveals insights into clonal development of prostate cancers and indicates loss of PTEN as a marker of poor prognosis. AB - Gauging the risk of developing progressive disease is a major challenge in prostate cancer patient management. We used genetic markers to understand genomic alteration dynamics during disease progression. By using a novel, advanced, multicolor fluorescence in situ hybridization approach, we enumerated copy numbers of six genes previously identified by array comparative genomic hybridization to be involved in aggressive prostate cancer [TBL1XR1, CTTNBP2, MYC (alias c-myc), PTEN, MEN1, and PDGFB] in six nonrecurrent and seven recurrent radical prostatectomy cases. An ERG break-apart probe to detect TMPRSS2-ERG fusions was included. Subsequent hybridization of probe panels and cell relocation resulted in signal counts for all probes in each individual cell analyzed. Differences in the degree of chromosomal and genomic instability (ie, tumor heterogeneity) or the percentage of cells with TMPRSS2-ERG fusion between samples with or without progression were not observed. Tumors from patients that progressed had more chromosomal gains and losses, and showed a higher degree of selection for a predominant clonal pattern. PTEN loss was the most frequent aberration in progressers (57%), followed by TBL1XR1 gain (29%). MYC gain was observed in one progresser, which was the only lesion with an ERG gain, but no TMPRSS2-ERG fusion. According to our results, a probe set consisting of PTEN, MYC, and TBL1XR1 would detect progressers with 86% sensitivity and 100% specificity. This will be evaluated further in larger studies. PMID- 25131425 TI - Dissolution-enhanced luminescent bioassay based on inorganic lanthanide nanoparticles. AB - Conventional dissociation-enhanced lanthanide fluoroimmunoassays (DELFIA) using molecular probes suffer from a low labeling ratio of lanthanide ions (Ln(3+) ) per biomolecule. Herein, we develop a unique bioassay based on the dissolution enhanced luminescence of inorganic lanthanide nanoparticles (NPs). As a result of the highly concentrated Ln(3+) ions in a single Ln(3+) NP, an extremely high Ln(3+) labeling ratio can be achieved, which amplifies significantly the luminescence signal and thus improves the detection sensitivity compared to DELFIA. Utilizing sub-10 nm NaEuF4 NPs as dissolution-enhanced luminescent nanoprobes, we demonstrate the successful in vitro detection of carcinoembryonic antigen (CEA, an important tumor marker) in human serum samples with a record-low detection limit of 0.1 pg mL(-1) (0.5 fM). This value is an improvement of approximately 3 orders of magnitude relative to that of DELFIA. The dissolution enhanced luminescent bioassay shows great promise in versatile bioapplications, such as ultrasensitive and multiplexed in vitro detection of disease markers in clinical diagnosis. PMID- 25131426 TI - Construction and evaluation of a genetic construct for specific detection and measurement of propionate by whole-cell bacteria. AB - Anaerobic digestion is a microbiological technology that converts biomass wastes into biogas, achieving both waste treatment and bioenergy production. Accumulation of volatile fatty acids (VFA) during acidogenesis, particularly propionate, often causes upset or failure of digesters. Early detection and monitoring of propionate concentration in digesters allow for just-in-time interventions to prevent irreversible costly process breakdown. In an attempt to develop a rapid method of measuring propionate concentration and bioavailability, we constructed a genetic construct for specific detection of bioavailable propionate. The genetic construct was constructed by transcriptional fusion of the regulatory gene (prpR) and the promoter of the prp operon (PprpB ) of Escherichia coli W3110 with the reporter gene cassette luxCDABE. When the genetic construct was carried on a plasmid and transformed into E. coli (referred to as plasmid-based biosensor), it resulted in stronger emission of luminescence than when it was inserted into the chromosome of E. coli (referred to as chromosome based biosensor). The biosensor responded specifically to propionate. The luminescence signal increased linearly with increasing concentration of propionate from 1 to 10 mM. The utility of the biosensor was evaluated using samples collected from anaerobic digesters. Once instrumented in future studies, the whole-cell bacterial biosensor developed in this study may provide an alternative technology for real-time detection and measurement of propionate in digesters. PMID- 25131427 TI - High doses of benzodiazepine predict analgesic and sedative drug withdrawal syndrome in paediatric intensive care patients. AB - AIM: Critically ill children can develop withdrawal syndrome after prolonged analgesia and sedation in a paediatric intensive care unit (PICU), when treatment is stopped abruptly or reduced quickly. The aim of this study was to evaluate the incidence of withdrawal syndrome in patients after three or more days of analgesic or sedative drug therapy, using a validated scale. We also analysed the association between withdrawal syndrome and the patients' outcome and factors related to analgesia and sedation treatment. METHODS: This prospective observational study analysed 89 periods of weaning from analgesia and sedation in 60 children between October 2010 and October 2011. Of these, 65% were less than six months old and 45% were admitted to the PICU after heart surgery. Withdrawal syndrome was assessed using the Withdrawal Assessment Tool-1 (WAT-1) scale. RESULTS: The incidence of withdrawal syndrome was 37%, and the only variable that predicted its presence was the highest administered dose of benzodiazepine. The duration of weaning, Sophia Observational Withdrawal Symptom scale score and nurse judgment were also associated with positive WAT-1 scores. CONCLUSION: Withdrawal syndrome should be considered after three or more days of analgesic or sedative treatment. A high dose of benzodiazepine increases the risk of developing withdrawal symptoms. PMID- 25131428 TI - Pharmacokinetic modeling and Monte Carlo simulation of ondansetron following oral administration in dogs. AB - Ondansetron is a potent antiemetic drug that has been commonly used to treat acute and chemotherapy-induced nausea and vomiting (CINV) in dogs. The aim of this study was to perform a pharmacokinetic analysis of ondansetron in dogs following oral administration of a single dose. A single 8-mg oral dose of ondansetron (Zofran((r)) ) was administered to beagles (n = 18), and the plasma concentrations of ondansetron were measured by liquid chromatography-tandem mass spectrometry. The data were analyzed by modeling approaches using ADAPT5, and model discrimination was determined by the likelihood-ratio test. The peak plasma concentration (Cmax ) was 11.5 +/- 10.0 ng/mL at 1.1 +/- 0.8 h. The area under the plasma concentration vs. time curve from time zero to the last measurable concentration was 15.9 +/- 14.7 ng.h/mL, and the half-life calculated from the terminal phase was 1.3 +/- 0.7 h. The interindividual variability of the pharmacokinetic parameters was high (coefficient of variation > 44.1%), and the one-compartment model described the pharmacokinetics of ondansetron well. The estimated plasma concentration range of the usual empirical dose from the Monte Carlo simulation was 0.1-13.2 ng/mL. These findings will facilitate determination of the optimal dose regimen for dogs with CINV. PMID- 25131429 TI - Development and evaluation of the Stages of Change in Oral Health instrument. AB - OBJECTIVES: Oral health personnel are limited in their ability to assess the readiness of patients to make changes to improve oral health. We aimed to develop and test the Stages of Change in Oral Health (SOCOH) model, a scaled index of the stages of change - pre-contemplative, contemplative or active - with particular emphasis on pregnancy. MATERIALS AND METHODS: Items were collected in a self report questionnaire conducted among a convenience sample of 446 mothers (age range: 14-43 years) pregnant with Aboriginal children in South Australia, Australia. Scales representing openness (four items; Cronbach's alpha = 0.73), value (four items; Cronbach's alpha = 0.71), inconvenience (six items; Cronbach's alpha = 0.79) and permissiveness (four items; Cronbach's alpha = 0.66) were developed. Participants were categorised according to the Stages of Change model and were evaluated against key self-reported oral health outcomes. RESULTS: Some 11.9% of participants were classified as pre-contemplators, 46.4% as contemplators and 41.7% as active. A higher proportion of active participants had a higher education, last visited a dentist less than a year previously, had no dental fear, owned a toothbrush, brushed the previous day, used toothpaste, had no difficulties paying a $100 dental bill, self-reported their dental health as 'excellent' and in the previous 12 months did not experience dental pain, embarrassment related to their dental appearance or difficulties eating food. CONCLUSIONS: The SOCOH model offers an internally consistent and valid instrument for detailed assessment of the readiness for change in regarding oral health behaviours in pregnancy and has potential benefits for clinical decision making and research. PMID- 25131430 TI - Anticonvulsants to treat post-traumatic stress disorder. AB - OBJECTIVE: We reviewed the existing literature on the efficacy of anticonvulsants in treating post-traumatic stress disorder. METHODS: We performed a literature search using PubMed, EMBASE and the Cochrane database on 30 September 2013. Randomized,controlled studies that investigated the efficacy of anticonvulsants for post-traumatic stress disorder were included in this review. Studies with retrospective designs, case reports and case series were excluded. RESULTS: A total of seven studies met the inclusion criteria for this review. Three studies used topiramate with negative findings regarding its efficacy. Two studies used divalproex, both of which failed to show superiority over placebo. One study used lamotrigine, with favourable results, and one study used tiagabine, with negative results. CONCLUSIONS: Future long-term studies with larger sample sizes are needed to investigate the clinical utility of anticonvulsants for posttraumatic stress disorder treatment. PMID- 25131431 TI - [Allopurinol and its role in the treatment of sarcopenia]. AB - Xanthine oxidase (XO) is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and uric acid and plays an important role in purine catabolism. The purine analogue, allopurinol, is a well-known inhibitor of XO widely used in the clinical management of gout and conditions associated with hyperuricemia. More recent data indicate that allopurinol reduces oxidative stress and improves vascular function in several cardiometabolic diseases, prolongs exercise time in angina, and improves the efficiency of cardiac contractility in heart failure. XO also plays an important role in free radical generation during skeletal muscle contraction and thus, it has been related to the muscle damage associated to exhaustive exercise. Several research groups have shown the protective effect of allopurinol in the prevention of this type of damage. Based on this background, a critical overview is presented on the possible role of allopurinol in the treatment of sarcopenia, a geriatric syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes, such as physical disability, poor quality of life and death. PMID- 25131432 TI - Body size evolution in Titanosauriformes (Sauropoda, Macronaria). AB - Titanosauriformes is a conspicuous and diverse group of sauropod dinosaurs that inhabited almost all land masses during Cretaceous times. Besides the diversity of forms, the clade comprises one of the largest land animals found so far, Argentinosaurus, as well as some of the smallest sauropods known to date, Europasaurus and Magyarosaurus. They are therefore good candidates for studies on body size trends such as the Cope's rule, the tendency towards an increase in body size in an evolutionary lineage. We used statistical methods to assess body size changes under both phylogenetic and nonphylogenetic approaches to identify body size trends in Titanosauriformes. Femoral lengths were collected (or estimated from humeral length) from 46 titanosauriform species and used as a proxy for body size. Our findings show that there is no increase or decrease in titanosauriform body size with age along the Cretaceous and that negative changes in body size are more common than positive ones (although not statistically significant) for most of the titanosauriform subclades (e.g. Saltasaridae, Lithostrotia, Titanosauria and Somphospondyli). Therefore, Cope's rule is not supported in titanosauriform evolution. Finally, we also found a trend towards a decrease of titanosauriform mean body size coupled with an increase in body size standard deviation, both supporting an increase in body size variation towards the end of Cretaceous. PMID- 25131433 TI - Involvement of NLRP3 inflammasome in rituximab-induced interstitial lung disease: a case report. AB - WHAT IS KNOWN AND OBJECTIVE: Rituximab is a chimeric anti-CD20 IgG1 monoclonal antibody for the treatment of various forms of lymphoma and haematological autoimmune diseases. Interstitial lung disease is a rare but lethal pulmonary toxicity of rituximab. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a molecular platform activated upon signs of cellular 'danger' to trigger the maturation of pro-inflammatory cytokines. We report the first case of rituximab-induced interstitial lung disease (R-ILD) with NLRP3 inflammasome activation in the lung. CASE SUMMARY: A 30-year-old male patient diagnosed with idiopathic thrombocytopenic purpura (ITP) was treated with four cycles of rituximab in one month. Three weeks after last rituximab administration, he developed progressive dyspnoea associated with respiratory failure, which was diagnosed as R-ILD. The patient showed a good response to steroid treatment, and lung biopsy was performed 5 days after the treatment. Immunohistopathological studies of lung specimens showed high expressions of inflammasome components NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 in lung interstitium with a heavy infiltration of CD19-positive cells. The levels of inflammasome-related cytokines IL-1beta and IL-18 in the serum were declined during the therapy. WHAT IS NEW AND CONCLUSIONS: This is the first report confirmed the role of NLRP3 inflammasome in pulmonary toxicity of rituximab. Inhibited activation of NLRP3 inflammasome in lung by steroid treatment could reverse R-ILD and block subsequent lung fibrosis. This result could open a new sight into the pathogenesis and provide a new target for the treatment of R-ILD. PMID- 25131437 TI - Alterations in collagen fibre patterns in breast cancer. A premise for tumour invasiveness? AB - Stromal tissue in the breast plays a key role in cancer invasiveness due to molecular and cellular changes. Collagen is the main component of the stroma. The purposes of this study were to investigate differences in collagen fibre patterns between tumour-induced stromal tissue and normal stroma, and between high-grade and low-grade breast cancer stroma, using second harmonic generation microscopy. Thirty-seven ductal carcinomas were examined: Twenty-one Luminal A phenotype and sixteen HER2 or Basal-like phenotype. Three regions were examined in each case: intratumoral, juxtatumoral and extratumoral. Two images were captured in each region. Two characteristics of collagen fibres were examined: the degree of straightness, and the degree of alignment. Collagen fibres were visually classified as curly, intermediate or straight, and as parallel or not parallel. The results of angle measurement and visual analysis showed that collagen fibres were straightest in the intratumoral region and curliest in the extratumoral region. Collagen fibres were more parallel in the juxtatumoral region compared to the two other regions. There were no significant differences between high-grade and low-grade tumours. As a breast tumour progresses, collagen fibres appear to straighten and align at the tumour boundary. This could facilitate invasion of the tumour into the surrounding stroma. PMID- 25131436 TI - Regulation of fatty acid biosynthesis by the global regulator CcpA and the local regulator FabT in Streptococcus mutans. AB - SMU.1745c, encoding a putative transcriptional regulator of the MarR family, maps to a location proximal to the fab gene cluster in Streptococcus mutans. Deletion of the SMU.1745c (fabTS m ) coding region resulted in a membrane fatty acid composition comprised of longer-chained, unsaturated fatty acids (UFA), compared with the parent strain. Previous reports have indicated a role for FabT in regulation of genes in the fab gene cluster in other organisms, through binding to a palindromic DNA sequence. Consensus FabT motif sequences were identified in S. mutans in the intergenic regions preceding fabM, fabTSm and fabK in the fab gene cluster. Chloramphenicol acetyltransferase (cat) reporter fusions, using the fabM promoter, revealed elevated transcription in a ?fabTS m background. Transcription of fabTS m was dramatically elevated in cells grown at pH values of 5 and 7 in the ? fabTS m background. Transcription of fabTS m was also elevated in a strain carrying a deletion for the carbon catabolite repressor CcpA. Purified FabTS m and CcpA bound to the promoter regions of fabTS m and fabM. Hence, the data indicate that FabTS m acts as a repressor of fabM and fabTS m itself and the global regulator CcpA acts as a repressor for fabTS m . PMID- 25131439 TI - The effect of calcium phosphate composite scaffolds on the osteogenic differentiation of rabbit dental pulp stem cells. AB - The objective of this study is to compare the effects of the two calcium phosphate composite scaffolds on the attachment, proliferation, and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs). One nano hydroxyapatite/collagen/poly (l-lactide) (nHAC/PLA), imitating the composition and the micro-structure characteristics of the natural bone, was made by Beijing Allgens Medical Science & Technology Co., Ltd. (China). The other beta-tricalcium phosphate (beta-TCP), being fully interoperability globular pore structure, was provided by Shanghai Bio-lu Biomaterials Co, Ltd. (China). We compared the absorption water rate and the protein adsorption rate of two scaffolds and the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment. The constructs were then implanted subcutaneously into the back of severely combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The results showed that the ODM-treated DPSCs expressed osteocalcin (OCN), bone sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by immunofluorescence staining. Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM-treated DPSCs. The absorption water rate and protein adsorption rate of nHAC/PLA was significantly higher than beta-TCP. The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto beta-TCP; and the proliferation rate of the cells was also significantly higher than that of beta-TCP on 1, 3, and 7 days of cell culture. The ALP activity, calcium/phosphorus content and mineral formation of DPSCs + beta-TCP were significantly higher than DPSCs + nHAC/LA. When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in beta TCP alone, DPSCs + nHAC/PLA and DPSCs + beta-TCP, and this three groups displayed increased bone formation over the 12-week period. The percentage of total bone formation area had no difference between DPSCs + beta-TCP and DPSCs + nHAC/PLA at each time point, but the percentage of mature bone formation area of DPSCs + beta TCP was significantly higher than that of DPSCs + nHAC/PLA. Our results demonstrated that the DPSCs on nHAC/PLA had a better proliferation, and that the DPSCs on beta-TCP had a more mineralization in vitro, much more newly formed mature bones in vivo were presented in DPSCs + beta-TCP group. These findings have provided a further knowledge that scaffold architecture has different influence on the attachment, proliferation and differentiation of cells. This study may provide insight into the clinical periodontal bone tissue repair with DPSCs + beta-TCP construct. PMID- 25131440 TI - Bi-compartmental elderly or adult dynamic digestion models applied to interrogate protein digestibility. AB - The world's population is inevitably ageing thanks to modern progress; however, the development of food and oral formulations tailored to the needs of the elderly is still in its infancy. In vitro digestion models offer high throughput, robust and practically ethics free evaluation of the digestive fate of ingested products. To date, no data have been made publicly available to facilitate the development or application of an in vitro model mirroring the physicochemical conditions of the elderly gastrointestinal system. This study reports the development of a novel and highly bio-relevant in vitro model based on two serially connected bioreactors recreating the dynamic conditions of the adult or elderly alimentary canal. This report and its supplementary material describe in detail the set-up of the system, the applied physicochemical parameters and the development of the controlling software. These are intended to openly depict a versatile platform, which could assist future efforts to develop age-tailored oral formulations. SDS-PAGE analyses of samples collected from the in vitro digestion of beta-lactoglobulin, alpha-lactalbumin and lactoferrin suggest the bioaccessibility of "slow digesting" and "fast digesting" proteins identified in adult models do not necessarily maintain this trait under elderly gastro intestinal conditions. Overall, this study brings forward a new generic yet advanced model that could facilitate age-tailoring the digestive fate of liquid formulations. PMID- 25131438 TI - Lipid interactions during virus entry and infection. AB - For entry and infection viruses have developed numerous strategies to subjugate indispensable cellular factors and functions. Host cell lipids and cellular lipid synthesis machinery are no exception. Not only do viruses exploit existing lipid signalling and modifications for virus entry and trafficking, they also reprogram lipid synthesis, metabolism, and compartmentalization for assembly and egress. Here we review these various concepts and highlight recent progress in understanding viral interactions with host cell lipids during entry and assembly. PMID- 25131441 TI - The role of the hippocampus in passive and active spatial learning. AB - Rats with lesions of the hippocampus or sham lesions were required in four experiments to escape from a square swimming pool by finding a submerged platform. Experiments 1 and 2 commenced with passive training in which rats were repeatedly placed on the platform in one corner-the correct corner-of a pool with distinctive walls. A test trial then revealed a strong preference for the correct corner in the sham but not the hippocampal group. Subsequent active training of being required to swim to the platform resulted in both groups acquiring a preference for the correct corner in the two experiments. In Experiments 3 and 4, rats were required to solve a discrimination between different panels pasted to the walls of the pool, by swimming to the middle of a correct panel. Hippocampal lesions prevented a discrimination being formed between panels of different lengths (Experiment 3), but not between panels showing lines of different orientations (Experiment 4); rats with sham lesions mastered both problems. It is suggested that an intact hippocampus is necessary for the formation of stimulus goal associations that permit successful passive spatial leaning. It is further suggested that an intact hippocampus is not necessary for the formation of stimulus-response associations, except when they involve information about length or distance. PMID- 25131442 TI - Short- and long-term prognosis of previous and new-onset atrial fibrillation in ST-segment elevation acute myocardial infarction. AB - INTRODUCTION AND OBJECTIVES: The impact of atrial fibrillation on the prognosis of myocardial infarction is still the subject of debate. We analyzed the influence of previous and new-onset atrial fibrillation on in-hospital and long term prognosis in patients with acute myocardial infarction. METHODS: Prospective study of 4284 patients with ST-segment elevation acute myocardial infarction. We studied all-cause in-hospital and long-term mortality (median, 7.2 years) using adjusted models. RESULTS: In total, 3.2% of patients had previous atrial fibrillation and 9.8% had new-onset atrial fibrillation. In general, both groups of patients had a high baseline risk profile and an increased likelihood of in hospital complications. The crude in-hospital mortality rate was higher in patients with previous atrial fibrillation than in those with new-onset atrial fibrillation (22% vs 12%; P<.001; 30% vs 10%; P<.001). The long-term mortality rate was 11.11/100 patient-years in patients with previous atrial fibrillation and 5.35/100 patient years in those with new-onset atrial fibrillation (both groups, P<.001). New-onset fibrillation alone (odds ratio=1.55; 95% confidence interval, 1.08-2.22) was an independent predictor of in-hospital mortality. Previous atrial fibrillation (hazard ratio=1.24; 95% confidence interval, 0.94 1.64) and new-onset atrial fibrillation (hazard ratio=0.98; 95% confidence interval, 0.80-1.21) were not independent predictors of long-term mortality. CONCLUSIONS: New-onset atrial fibrillation during hospitalization is an independent risk factor for in-hospital mortality in acute myocardial infarction. PMID- 25131443 TI - Ecological mechanisms underpinning climate adaptation services. AB - Ecosystem services are typically valued for their immediate material or cultural benefits to human wellbeing, supported by regulating and supporting services. Under climate change, with more frequent stresses and novel shocks, 'climate adaptation services', are defined as the benefits to people from increased social ability to respond to change, provided by the capability of ecosystems to moderate and adapt to climate change and variability. They broaden the ecosystem services framework to assist decision makers in planning for an uncertain future with new choices and options. We present a generic framework for operationalising the adaptation services concept. Four steps guide the identification of intrinsic ecological mechanisms that facilitate the maintenance and emergence of ecosystem services during periods of change, and so materialise as adaptation services. We applied this framework for four contrasted Australian ecosystems. Comparative analyses enabled by the operational framework suggest that adaptation services that emerge during trajectories of ecological change are supported by common mechanisms: vegetation structural diversity, the role of keystone species or functional groups, response diversity and landscape connectivity, which underpin the persistence of function and the reassembly of ecological communities under severe climate change and variability. Such understanding should guide ecosystem management towards adaptation planning. PMID- 25131444 TI - Abortion providers, stigma and professional quality of life. AB - OBJECTIVES: The Providers Share Workshop (PSW) provides abortion providers safe space to discuss their work experiences. Our objectives were to assess changes in abortion stigma over time and explore how stigma is related to aspects of professional quality of life, including compassion satisfaction, burnout and compassion fatigue for providers participating in the workshops. STUDY DESIGN: Seventy-nine providers were recruited to the PSW study. Surveys were completed prior to, immediately following and 1 year after the workshops. The outcome measures were the Abortion Provider Stigma Survey and the Professional Quality of Life (ProQOL) survey. Baseline ProQOL scores were compared to published averages using t tests. Changes in abortion stigma and aspects of professional quality of life were assessed by fitting a two-level random-effects model with repeated measures at level 1 (period-level) and static measures (e.g., demographic data) at level 2 (person-level). Potential covariates included age, parenting status, education, organizational tenure, job type and clinic type (stand-alone vs. hospital-based clinics). RESULTS: Compared to other healthcare workers, abortion providers reported higher compassion satisfaction (t=2.65, p=.009) and lower burnout (t=5.13, p<.0001). Repeated-measures analysis revealed statistically significant decreases in stigma over time. Regression analysis identified abortion stigma as a significant predictor of lower compassion satisfaction, higher burnout and higher compassion fatigue. CONCLUSIONS: Participants in PSW reported a reduction in abortion stigma over time. Further, stigma is an important predictor of compassion satisfaction, burnout and compassion fatigue, suggesting that interventions aimed at supporting the abortion providing workforce should likely assess abortion stigma. IMPLICATIONS: Stigma is an important predictor of compassion satisfaction, burnout and compassion fatigue among abortion care providers. Therefore, strengthening human resources for abortion care requires stigma reduction efforts. Participants in the PSWs show reductions in stigma over time. PMID- 25131445 TI - APRI and FIB-4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS). AB - We aim to determine the predictive ability of APRI, FIB-4 and AST/ALT ratio for staging of liver fibrosis and to differentiate significant fibrosis (F2-F4) from none to minimal fibrosis (F0-F1) in chronic hepatitis B (CHB). Liver biopsy results were mapped to an F0-4 equivalent fibrosis stage. Mean APRI and FIB-4 scores were significantly higher for each successive fibrosis level from F1 to F4 (P < 0.05). Based on optimized cut-offs, the AUROCs in distinguishing F2-F4 from F0 to F1 were 0.81 (0.76-0.87) for APRI, 0.81 (0.75-0.86) for FIB-4 and 0.56 (0.49-0.64) for AST/ALT ratio. APRI and FIB-4 distinguished F2-F4 from F0 to F1 with good sensitivity and specificity and can be useful for treatment decisions and monitoring progression of fibrosis. PMID- 25131447 TI - Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke. AB - Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke elicited pressor response. Experiments were performed in male adult Sprague Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang (1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response. PMID- 25131446 TI - Deep brain stimulation in rats: different targets induce similar antidepressant like effects but influence different circuits. AB - Recent studies in patients with treatment-resistant depression have shown similar results with the use of deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG), ventral capsule/ventral striatum (VC/VS) and nucleus accumbens (Acb). As these brain regions are interconnected, one hypothesis is that by stimulating these targets one would just be influencing different relays in the same circuitry. We investigate behavioral, immediate early gene expression, and functional connectivity changes in rats given DBS in homologous regions, namely the ventromedial prefrontal cortex (vmPFC), white matter fibers of the frontal region (WMF) and nucleus accumbens. We found that DBS delivered to the vmPFC, Acb but not WMF induced significant antidepressant-like effects in the FST (31%, 44%, and 17% reduction in immobility compared to controls). Despite these findings, stimulation applied to these three targets induced distinct patterns of regional activity and functional connectivity. While animals given vmPFC DBS had increased cortical zif268 expression, changes after Acb stimulation were primarily observed in subcortical structures. In animals receiving WMF DBS, both cortical and subcortical structures at a distance from the target were influenced by stimulation. In regard to functional connectivity, DBS in all targets decreased intercorrelations among cortical areas. This is in contrast to the clear differences observed in subcortical connectivity, which was reduced after vmPFC DBS but increased in rats receiving Acb or WMF stimulation. In conclusion, results from our study suggest that, despite similar antidepressant-like effects, stimulation of the vmPFC, WMF and Acb induces distinct changes in regional brain activity and functional connectivity. PMID- 25131448 TI - Folate deficiency-induced oxidative stress contributes to neuropathy in young and aged zebrafish--implication in neural tube defects and Alzheimer's diseases. AB - Folate is a nutrient essential for the development, function and regeneration of nervous systems. Folate deficiency has been linked to many neurological disorders including neural tube defects in fetus and Alzheimer's diseases in the elderly. However, the etiology underlying these folate deficiency-associated diseases is not completely understood. In this study, zebrafish transgenic lines with timing and duration-controllable folate deficiency were developed by ectopically overexpressing a recombinant EGFP-gamma-glutamyl hydrolase (gammaGH). Impeded neural crest cell migration was observed in the transgenic embryos when folate deficiency was induced in early stages, leading to defective neural tube closure and hematopoiesis. Adding reduced folate or N-acetylcysteine reversed the phenotypic anomalies, supporting the causal link between the increased oxidative stress and the folate deficiency-induced abnormalities. When folate deficiency was induced in aged fish accumulation of beta-amyloid and phosphorylated Tau protein were found in the fish brain cryo-sections. Increased autophagy and accumulation of acidic autolysosome were apparent in folate deficient neuroblastoma cells, which were reversed by reduced folate or N-acetylcysteine supplementation. Decreased expression of cathepsin B, a lysosomal protease, was also observed in cells and tissue with folate deficiency. We concluded that folate deficiency-induced oxidative stress contributed to the folate deficiency associated neuropathogenesis in both early and late stages of life. PMID- 25131450 TI - Use of Sato's curved laryngoscope and an insulated-tip knife for endoscopic incisional therapy of esophageal web. AB - We experienced two cases of esophageal web accompanying severe stricture that were treated by endoscopic incisions with an insulated-tip knife (IT-knife). With attention paid to the mucosa at the stricture, the lesion was incised with an IT knife without complications. Sato's curved laryngoscope was used even in cervical esophageal lesions and an excellent field was secured. PMID- 25131451 TI - Relationship of hyperinsulinaemia, insulin resistance and beta-cell dysfunction with incident diabetes and pre-diabetes: the Tehran Lipid and Glucose Study. AB - AIMS: To examine the association of fasting insulin, insulin resistance and reduced beta-cell function with incident Type 2 diabetes and pre-diabetes (isolated impaired fasting glucose/isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance). METHODS: An Iranian population comprising 1532 men and 2221 women, aged >= 20 years, with normal fasting glucose and normal glucose tolerance at baseline, were enrolled in the study. Multivariable Cox proportional hazard models were used to calculate the hazard ratios and 95% CIs of fasting insulin, updated homeostasis model assessments of insulin resistance and beta-cell function for incident Type 2 diabetes, isolated impaired fasting glucose, isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance. RESULTS: During a median follow-up of 9.2 years, the annual incidence rates (95% CI) of diabetes were 3.73 (2.74-4.94) and 4.06 (3.21-5.06) per 1000 person-years in men and women, respectively. In both men and women, fasting insulin and homeostasis model assessment of insulin resistance (>= 75th percentile) were significantly associated with incident diabetes and combined impaired fasting glucose/impaired glucose tolerance; however, reduced beta-cell function as measured by homeostasis model assessment of beta-cell function (< 25th percentile) was associated with incident isolated impaired fasting glucose solely in men [hazard ratio 1.35 (95% CI 1.02-1.78)] in multivariable analysis including waist-hip ratio). Hyperinsulinaemia, insulin resistance and beta-cell dysfunction were not related to the incidence of isolated impaired glucose tolerance in either gender. CONCLUSIONS: Fasting hyperinsulinaemia and insulin resistance were strong risk factors for progression to diabetes and combined impaired fasting glucose/impaired glucose tolerance in a population with normal fasting glucose/normal glucose tolerance. In addition, impaired beta-cell function at baseline was related to the development of isolated impaired fasting glucose only in men and, in both men and women, neither insulin resistance nor beta-cell dysfunction were associated with incident isolated impaired glucose tolerance. PMID- 25131452 TI - Genetic history of hepatitis C virus in Pakistan. AB - Hepatitis C virus (HCV) genotype 3a accounts for ~80% of HCV infections in Pakistan, where ~10 million people are HCV-infected. Here, we report analysis of the genetic heterogeneity of HCV NS3 and NS5b subgenomic regions from genotype 3a variants obtained from Pakistan. Phylogenetic analyses showed that Pakistani genotype 3a variants were as genetically diverse as global variants, with extensive intermixing. Bayesian estimates showed that the most recent ancestor for genotype 3a in Pakistan was last extant in ~1896-1914 C.E. (range: 1851 1932). This genotype experienced a population expansion starting from ~1905 to ~1970 after which the effective population leveled. Death/birth models suggest that HCV 3a has reached saturating diversity with decreasing turnover rate and positive extinction. Taken together, these observations are consistent with a long and complex history of HCV 3a infection in Pakistan. PMID- 25131453 TI - Effects of three different low-intensity exercise interventions on physical performance, muscle CSA and activities of daily living: a randomized controlled trial. AB - OBJECTIVES: To evaluate the short-term effects of three different resistance training programs, conducted at low intensity, on physical performance, muscle cross-sectional area (CSA) and the capacity to perform daily tasks in older adults living in a geriatric nursing home. DESIGN: Randomized controlled trial, with a 4-month intervention period. SETTING: A geriatric nursing home in Valencia, Spain. PARTICIPANTS: Eighty-nine adults aged 75 to 96 who were independent in their daily activities. INTERVENTION: After a baseline assessment, the participants were randomly assigned to the control group or one of the three intervention groups: volitional contraction (VC; n=22), neuromuscular electrical stimulation (NMES; n=22), or neuromuscular electrical stimulation superimposed onto voluntary contractions (NMES+; n=22). The intervention focused on knee extension exercises and its intensity was set at 40% of one-repetition maximum (1RM). MEASUREMENTS: The primary outcome measure was mobility. Secondary outcomes were rectus femoris CSA, balance, aerobic endurance, upper-body strength and the capacity to perform daily tasks. All data were collected at baseline and after the 4-month intervention period. RESULTS: The two-way ANOVA analysis showed a significant group*time interaction effect for the mobility (P=.022), rectus femoris CSA (P=.001), and the capacity to perform daily tasks (P=.05). The within group analysis found a more prominent effect in the NMES+ group. Significant improvements were seen in rectus femoris CSA and the capacity to perform daily tasks in all intervention groups. Mobility only improved in the NMES+ group (P=.026). CONCLUSION: From a short-term perspective, NMES+ exercise training, performed at low intensity, can improve physical performance, muscle CSA, and the capacity to perform daily activities, and to partially mitigate age-related consequences in older adults. PMID- 25131454 TI - Testicular hypofunction and multiple sclerosis risk: a record-linkage study. AB - The influence of gonadal hormones on multiple sclerosis (MS) is not well characterized and has thus far been investigated primarily in animal models or as a proposed therapeutic approach. We investigated a potential association between testicular hypofunction, as a proxy for low testosterone levels, and MS risk through analysis of linked English national Hospital Episode Statistics from 1999 to 2011. We report a strong positive association between testicular hypofunction and subsequent MS (rate ratio = 4.62, 95% confidence interval = 2.3-8.24, p < 0.0001). Future work should aim more directly to elucidate the relationship between testosterone levels and MS in both males and females. PMID- 25131456 TI - A facilely synthesized amino-functionalized metal-organic framework for highly specific and efficient enrichment of glycopeptides. AB - A facilely synthesized amino-functionalized metal-organic framework (MOF) MIL 101(Cr)-NH2 was first applied for highly specific glycopeptide enrichment based on the hydrophilic interactions. With the special characteristics of the MOF, the material performed well in selectivity and sensitivity for both standard glycoprotein samples and complex biological samples. PMID- 25131449 TI - HDL and cognition in neurodegenerative disorders. AB - High-density lipoproteins (HDLs) are a heterogeneous group of lipoproteins composed of various lipids and proteins. HDL is formed both in the systemic circulation and in the brain. In addition to being a crucial player in the reverse cholesterol transport pathway, HDL possesses a wide range of other functions including anti-oxidation, anti-inflammation, pro-endothelial function, anti-thrombosis, and modulation of immune function. It has been firmly established that high plasma levels of HDL protect against cardiovascular disease. Accumulating evidence indicates that the beneficial role of HDL extends to many other systems including the central nervous system. Cognition is a complex brain function that includes all aspects of perception, thought, and memory. Cognitive function often declines during aging and this decline manifests as cognitive impairment/dementia in age-related and progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. A growing concern is that no effective therapy is currently available to prevent or treat these devastating diseases. Emerging evidence suggests that HDL may play a pivotal role in preserving cognitive function under normal and pathological conditions. This review attempts to summarize recent genetic, clinical and experimental evidence for the impact of HDL on cognition in aging and in neurodegenerative disorders as well as the potential of HDL-enhancing approaches to improve cognitive function. PMID- 25131457 TI - Self-aggregation of synthetic zinc chlorophyll derivatives possessing 3(1) hydroxy or methoxy group and 13(1)-mono- or dicyanomethylene moiety in nonpolar organic solvents as models of chlorosomal bacteriochlorophyll-d aggregates. AB - Methyl 13(1)-(di)cyanomethylene-pyropheophorbides were synthesized by Knoevenagel reactions of the corresponding 13(1)-oxo-chlorins prepared from modifying chlorophyll-a with malononitrile or cyanoacetic acid. Alternatively, methyl 13(1) cyanomethylene-pyropheophorbides were produced by Wittig reactions of 13(1)-oxo chlorins with Ph3P=CHCN. Self-aggregation of zinc complexes of the semi-synthetic chlorophyll derivatives possessing a hydroxy or methoxy group at the 3(1) position was examined in 1%(v/v) tetrahydrofuran or dichloromethane and hexane by electronic absorption and circular dichroism spectroscopy. Although intermolecular hydrogen-bonding between the 3(1)-hydroxy and 13(1)-oxo groups of bacteriochlorophylls-c/d/e/f was essential for their self-aggregation in natural light-harvesting antenna systems (=chlorosomes), zinc 3(1)-hydroxy-13(1) di/monocyanomethylene-chlorins self-aggregated in the less/lesser polar organic solvents to form chlorosome-like large oligomers in spite of lacking the 13(1) oxo moiety as the hydrogen-bonding acceptor. Zinc 3(1)-methoxy-13(1) dicyanomethylene-chlorin gave similar self-aggregates regardless of lack of both the 3(1)-hydroxy and 13(1)-oxo groups. The present self-aggregation was ascribable to stronger coordination of the 3(1)-oxygen atom to the central zinc than the conventional systems, where the electron-withdrawing cyano group(s) increased the coordinative ability of the central zinc through the chlorin pi system. PMID- 25131459 TI - [Transperitoneal laparoscopic ureteral reimplantation with extracorporeal tailoring and direct nipple ureteroneocystostomy for adult obstructive megaureter]. AB - This paper focuses on a novel modified technique about the treatment of adult obstructed megaureter by the transperitoneal laparoscopic procedure. With the improvement of the laparoscopic surgery, many urological surgeries can be safely and effectually performed by laparoscopic approach. The previously reported laparoscopic methods for treatment of adult obstructed megaureter were complex and time-consuming. To simplify the method, we modified the laparoscopic approach based on the previous methods. The innovative points of our novel technique are the extracorporeal tailoring of ureter and nipple ureteroneocystostomy. By this modified procedure, the time of operation can be obviously reduced while the procedure is effective. We hope this modified procedure will be accepted by more urologists. PMID- 25131460 TI - [Incidence and clinicopathological characteristics of incidental prostatic adenocarcinoma in radical cystoprostatectomy specimens]. AB - OBJECTIVE: To analyze the incidence and clinicopathological features of incidental prostate cancer (IPCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. METHODS: We retrospectively reviewed the histopathological features of 865 male patients who underwent an RCP between January 2005 and March 2014. No patients had preoperative clinical or biological suspicion of prostate cancer (PCa). RESULTS: Among the 865 specimens, IPCa was diagnosed in 235 patients (27.2%). Most tumors (228/235, 97.0%) were organ confined (pT2); And 7 cases (3.0 %) of them were diagnosed at T3. Gleason score was < 6 in 84 cases (35.7 %), 6 in 77 cases (32.8%), 7 in 64 cases (27.2 %), and > 7 in 10 cases (4.3 %). CONCLUSION: The rate of incidentally diagnosed IPCa was 8.5%, and that in RCP and TURP specimens was 19.5% and 4.4% respectively. The majority of these IPCas were organ-confined. Gleason score in most of these specimens was <= 7. Moreover, prostate examination in the RCP specimen should be careful and sufficient, whole-amount prostate sections improve diagnostic accuracy. PMID- 25131455 TI - Endothelin@25 - new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR Review 12. AB - Since the discovery of endothelin (ET)-1 in 1988, the main components of the signalling pathway have become established, comprising three structurally similar endogenous 21-amino acid peptides, ET-1, ET-2 and ET-3, that activate two GPCRs, ETA and ETB . Our aim in this review is to highlight the recent progress in ET research. The ET-like domain peptide, corresponding to prepro-ET-193-166 , has been proposed to be co-synthesized and released with ET-1, to modulate the actions of the peptide. ET-1 remains the most potent vasoconstrictor in the human cardiovascular system with a particularly long-lasting action. To date, the major therapeutic strategy to block the unwanted actions of ET in disease, principally in pulmonary arterial hypertension, has been to use antagonists that are selective for the ETA receptor (ambrisentan) or that block both receptor subtypes (bosentan). Macitentan represents the next generation of antagonists, being more potent than bosentan, with longer receptor occupancy and it is converted to an active metabolite; properties contributing to greater pharmacodynamic and pharmacokinetic efficacy. A second strategy is now being more widely tested in clinical trials and uses combined inhibitors of ET-converting enzyme and neutral endopeptidase such as SLV306 (daglutril). A third strategy based on activating the ETB receptor, has led to the renaissance of the modified peptide agonist IRL1620 as a clinical candidate in delivering anti-tumour drugs and as a pharmacological tool to investigate experimental pathophysiological conditions. Finally, we discuss biased signalling, epigenetic regulation and targeting with monoclonal antibodies as prospective new areas for ET research. PMID- 25131461 TI - [Expression of brainderived neurotrophic factor in urine of patients with benign prostatic hyperplasia complicated overactive bladder symptoms]. AB - OBJECTIVE: To investigate the expression of urinary brainderived neurotrophic factor (BDNF) in benign prostatic hyperplasia patients with overactive bladder (OAB) symptoms and its correlation with the severity of OAB symptoms. METHODS: According to the inclusion and exclusion criteria, a total of 178 patients with benign prostatic hyperplasia who were to undergo transurethral resection of prostate (TURP) were enrolled in this study. All the patients had accepted basic preoperative evaluations, as well as an assessment of their International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS). The patients who had been scheduled for surgery had to take the urodynamic assessment. Urinary BDNF levels were measured by the enzyme-linked immunosorbent assay (ELISA) and the results were further normalized to the concentration of urinary creatinine (BDNF/Cr, mg/mol). RESULTS: The urinary BDNF/Cr levels of the patients with moderate and severe lower urinary tract symptoms were (1.189 +/- 0.753) mg/mol and (1.817 +/- 1.110) mg/mol (P < 0.001). The urinary BDNF/Cr levels of the patients with grades III-VI obstruction were (1.382 +/- 0.945) mg/mol, (1.435 +/- 0.938) mg/mol, (1.640 +/- 1.104) mg/mol, and (1.653 +/- 1.019) mg/mol, respectively (P > 0.05). There was no correlation between the urinary BDNF/Cr levels and the severity of obstruction (r = 0.103, P = 0.173). The urinary BDNF/Cr levels in the patients with and without OAB symptoms were (1.913 +/- 0.843) mg/mol and (0.297 +/- 0.183) mg/mol (P < 0.001). The urinary BDNF/Cr levels in the patients with mild, moderate and severe OAB symptoms were (1.501 +/ 0.543) mg/mol, (1.806 +/- 0.703) mg/mol and (2.560 +/- 0.979) mg/mol, respectively (P < 0.05). There was a correlation between the urinary BDNF/Cr levels and the severity of OAB symptoms (r = 0.743, P < 0.001). The urinary BDNF/Cr levels in the patients with urodynamic detrusor overativity were significantly higher than those without detrusor overativity [(1.917 +/- 0.866) mg/mol and (1.194 +/- 1.013) mg/mol, P < 0.001]. CONCLUSION: There is no correlation between urinary BDNF and severity of obstruction in benign prostatic hyperplasia patients with moderate and severe lower urinary tract symptoms. The urinary BDNF levels in patients with OAB symptoms are elevated compared with patients without OAB symptoms, and are correlated with the severity of OAB symptoms. PMID- 25131462 TI - [Characteristics of lymph node metastasis in patients undergoing radical cystectomy for bladder cancer: a retrospective single-center study of 522 cases]. AB - OBJECTIVE: To investigate the characteristics and related influence factors of lymph node metastases in patients undergoing radical cystectomy and lymph node dissection for bladder cancer. METHODS: The data of 522 patients who underwent radical cystectomy and pelvic lymph node dissection at Department of Urology, Peking University First Hospital from 1998 to 2012, were retrospectively collected, and the lymph node mapping was performed in all the patients to determine the location of metastatic lymph nodes. RESULTS: For the 522 patients with bladder cancer, lymph node metastasis occurred in 99 patients, and the incidence of lymph node metastasis was 19.0%. The incidence at different tumor stages was: 3.7% in T1 (6/164), 10.5% in T2 (17/160), 36.7% in T3(40/107), and 41.9% in T4 (36/86). The most common involved lymph nodes were hypogastric/obturator lymph nodes (77/99, 77.8%) and external iliac lymph nodes (35/99, 35.4%). The mean number of lymph nodes dissected was 11.6 (1-51). The lymph node density (number of lymph nodes involved/number of lymph nodes removed) was 44.1%. The incidence of lymph node metastasis was statistical related to tumor stage (P < 0.01, OR 2.71,95% CI 2.13-3.44) and tumor grade (P < 0.01, OR 3.81,95% CI 1.66-8.74), while age, gender, smoke history, and weight had no statistical significance. CONCLUSION: Lymph node metastasis is the most common metastasis route of bladder cancer. The incidence of lymph node tumor involvement is correlated with increasing tumor stage and tumor grade. The most common involved lymph nodes are hypogastric/obturator lymph nodes and external iliac lymph nodes. Radical cystectomy and bilateral pelvic lymph nodes dissection are of great significance in the treatment of bladder cancer. PMID- 25131463 TI - [Long-term outcome of isolated local recurrence following radical nephrectomy]. AB - OBJECTIVE: To characterize the long-term outcome of surgical extirpation for local recurrence after radical nephrectomy of renal cell carcinoma (RCC) and identify prognostic factors for locally recurrent RCC. METHODS: Peking University First Hospital urologic database was queried for all patients with isolated local recurrence following radical nephrectomy for localized RCC. According to previous literature, local recurrence included relapse in the renal fossa, ipsilateral adrenal gland and ipsilateral retroperitoneal lymph nodes. The median follow up was 62 months. The cancer specific survival and relapse patterns were estimated using the Kaplan-Meier method. RESULTS: In our institutional database,1 045 patients were treated with nephrectomy for localized RCC from January 1994 to December 2011.With a postoperative follow-up of (62.7 +/- 36.2) months, 15 patients (1.44%) experienced local recurrence, 9 of which were managed by surgical resection, and the rest 6 did not receive operation. The patients who received surgical resection had a 1-year cancer specific survival rate of 87%, compared with 60% of the patients without receiving surgical treatment. The 4 year cancer specific survival rate was 72% vs. 30%.The survival time was(51.8 +/- 7.4) months vs. (28.4 +/- 9.2) months. The recurrence interval was (39.4 +/- 29.5) months vs. (29.3 +/- 23.9) months. CONCLUSION: Surgical resection for local recurrence of RCC in selected patients is a feasible management and may prolong the survival time. PMID- 25131458 TI - Endogenous versus exogenous markers of adult neurogenesis in canaries and other birds: advantages and disadvantages. AB - Although the existence of newborn neurons had originally been suggested, but not broadly accepted, based on studies in adult rodent brains, the presence of an active neurogenesis process in adult homoeothermic vertebrates was first firmly established in songbirds. Adult neurogenesis was initially studied with the tritiated thymidine technique, later replaced by the injection and detection of the marker of DNA replication 5-bromo-2'-deoxyuridine (BrdU). More recently, various endogenous markers were used to identify young neurons or cycling neuronal progenitors. We review here the respective advantages and pitfalls of these different approaches in birds, with specific reference to the microtubule associated protein, doublecortin (DCX), that has been extensively used to identify young newly born neurons in adult brains. All these techniques of course have limitations. Exogenous markers label cells replicating their DNA only during a brief period and it is difficult to select injection doses that would exhaustively label all these cells without inducing DNA damage that will also result in some form of labeling during repair. On the other hand, specificity of endogenous markers is difficult to establish due to problems related to the specificity of antibodies (these problems can be, but are not always, addressed) and more importantly because it is difficult, if not impossible, to prove that a given marker exhaustively and specifically labels a given cell population. Despite these potential limitations, these endogenous markers and DCX staining in particular clearly represent a useful approach to the detailed study of neurogenesis especially when combined with other techniques such as BrdU. PMID- 25131464 TI - [Effects of interval time between prostate biopsy and surgery on laparoscopic radical prostatectomy]. AB - OBJECTIVE: To investigate the length of interval time between biopsy and laparascopic radical prostatectomy in difficulty and effects of surgery. METHODS: We retrospectively analyzed 89 cases of laparascopic radical prostatectomy from June 2011 to September 2013. The patients were divided into two groups according to the interval time of 6 weeks. The mean interval time was 3.1 weeks (ranging from 1.5 to 4.4 weeks) in group IT< 6 weeks and 4.4 weeks (ranging from 6.0 to 16.2 weeks) in group IT >= 6 weeks. The mean age was 67 years (ranging from 57 to 78 years). The PSA level was 15.4 MUg/L (ranging from 5.2 to 72.0). The prostate volume was 55 mL (ranging from 42 to 89 mL). The parameters, such as operation duration, blood loss, positive surgical margin rate, incharge time postoperation, were evaluated. RESULTS: All the surgeries went successfully. The average operation duration was 150 min (ranging from 110 to 242 min), and the blood loss was 230 mL (ranging from 100 to 750 mL). The positive surgical margin rate was 18% and the urinary continence rate was 100% at 3 months after operation. The clinical recurrence was not found during the follow-up. No significant difference was found between the groups in the patients' age, preoperative PSA, Gleason score and prostate volume (P > 0.05). No statistical significance existed in the operation time, blood loss, positive margin rate, post-operative hospital stay, urinary continence rate at 3 months after operation, postoperative differences of clinical recurrence rates. CONCLUSION: The length of interval time between prostate biopsy and laparascopic radical prostatectomy does not influence the difficulty and effect in the early stage, and the long time survival and recurrent rate need further observation. PMID- 25131465 TI - [Technique of renal pedicle control in transperitoneal laparoscopic nephrectomy: experience of 191 cases by a single surgeon]. AB - OBJECTIVE: To explore the technique of vascular control in transperitoneal laparoscopic nephrectomy. METHODS: From May 2010 to September 2013, 191 consecutive transperitoneal laparoscopic nephrectomies were performed by a single surgeon. The operations included 116 radical nephrectomies, 57 nephroureterectomies, and 18 simple nephrectomies. Improved 4-trocar method was applied. Through lifting up inferior pole of the kidney by an assistant, and observing renal vascular from the bottom or back of the kidney, the exposure of renal vessels were improved. The renal vessels were managed with Hem-o-lock or Endo GIA. For tumors of stage >= T2, ipsilateral lymph node dissection of renal hilus was performed. RESULTS: Of the entire 191 cases,190 were performed successfully, only 1 converted to open surgery because of the difficulty in separating the tumor from the invaded colon. The average time of operation was 171.5 min (74-352). The blood loss was 5-1 000 mL with an average of 94.8 mL. The complications included vascular injuries (5 cases), cerebral infarction accompanied by acute renal injury (1 case), and pulmonary infection (2 cases). The mean postoperative hospital stay was 5.6 days (2-19 days). No perioperative death occurred. CONCLUSION: The reformative technique of vascular control could improve the exposure of renal vessels, increase surgery safety, and shorten the time of transperitoneal laparoscopic nephrectomy. PMID- 25131466 TI - [Comparison of the outcomes of microscopic varicocelectomy and laparoscopic varicocelectomy]. AB - OBJECTIVE: To compare and analyze semen quality improvement between the patients with microscopic varicocelectomy and laparoscopic varicocelectomy. METHODS: A total of 291 patients with varicocele were included in this study, of whom 176 underwent microscopic varicocelectomy and 115 laparoscopic varicocelectomy. The improvement rates of semen quality and pregnancy rates between the two groups were compared. RESULTS: The improvement rate of sperm density in microscopic group was significantly higher than that of laparoscopic group (87.6% vs. 73.7%, P = 0.006). Spouse pregnancy rate of microscopic group was significantly higher than that of laparoscopic group (45.4% vs. 30.3%, P = 0.017). CONCLUSION: The effect of microscopic varicocelectomy was superior to that of laparoscopic varicocelectomy. PMID- 25131467 TI - [Analysis for related factors of upper urinary tract deterioration in patients with spinal cord injury]. AB - OBJECTIVE: To evaluate the related factors of upper urinary tract deterioration in spinal cord injured patients. METHODS: Medical records of spinal cord injured patients from Jan.2002 to Sep.2009 were retrospectively reviewed. All the patients were divided into the upper urinary tract deterioration group and non deterioration group according to the diagnostic criteria. Indexes such as demographic characteristic (gender, age), spinal cord injury information (cause, level, completeness), statuses of urinary tract system (bladder management, urine routine, urine culture, ultrasound, serum creatinine, fever caused by urinary tract infection) and urodynamics information(bladder compliance, bladder stability, bladder sensation, detrusor sphincter dyssynergia, detrusor leak point pressure, maximum cystometric capacity, relative safe bladder capacity, maximum flow rate, maximum urethra closure pressure) were compared between the two groups.Then Logistic regression analysis were performed. RESULTS: There was significantly difference between the two groups in spinal cord injury level(chi(2) = 8.840, P = 0.031),bladder management(chi(2) = 11.362, P = 0.045), urinary rutine(chi(2) = 17.983, P = 0.000), fever caused by urinary tract infection(chi(2)= 64.472, P = 0.000), bladder compliance(chi(2) = 6.531, P = 0.011), bladder sensation(chi(2) = 11.505, P = 0.009), maximum cystometric capacity(t = 2.209, P = 0.043), and detrusor-sphincter dyssynergia(chi(2) = 4.247, P = 0.039). The multiple-factor non-conditional Logistic regression analysis showed that bladder management (OR = 1.114, P = 0.006), fever caused by urinary tract infection(OR = 1.018,P = 0.000), bladder compliance (OR = 1.588, P = 0.040) and detrusor-sphincter dyssynergia(OR = 1.023, P = 0.034) were the key factors of upper urinary tract deterioration in spinal cord injured patients. CONCLUSION: Urinary tract infection, lower bladder compliance, detrusor-sphincter dyssynergia and unreasonable bladder management are the risk factors of upper urinary tract deterioration in spinal cord injured patients. PMID- 25131468 TI - [Ureteral stricture following renal transplantation: risk factors and surgical management]. AB - OBJECTIVE: To evaluate the prevalence and the risk factors of the ureteral stricture following renal transplantation and outcomes of surgical managements. METHODS: By a retrospective analysis, we assessed 1 293 patients who underwent renal transplantation between January 2001 and December 2013 at our center. The patients with ureteral stricture had undergone surgical management which included neoureterocystostomy, ureteral anastomosis with the native ureter and endoscopic therapy. RESULTS: Ureteral stricture following renal transplantation was diagnosed in 17 cases (1.3%) including 6 males and 11 females. The mean age of the patients at the time of surgery was 44 (29 to 64) years. The median interval between ureteral stricture obstruction and kidney transplantation was 4 (1 to 120) months. The ureteral stricture was significantly correlated with multiple renal arteries, donor age and delayed graft function. The effective rate of surgical management was 65.75%. CONCLUSION: The incidence of ureteral stricture as a urologic complication after renal transplantation is low. The advanced techniques that preserve the ureteric blood supply should be applied. The surgical managements have respective advantages and disadvantages. The neoureterocystostomy shows best outcome, while ureteral anastomosis with the native ureter has poor outcome. PMID- 25131469 TI - [Pathogenesis and therapy of hydronephrosis after hematopoietic stem cell transplantation]. AB - OBJECTIVE: To investigate the pathogenesis and therapy of hydronephrosis after hematopoietic stem cell transplantation (HSCT). METHODS: From March 2004 to March 2014, 23 patients with hydronephrosis after HSCT were identified. With these data, the pathogenesis of hydronephrosis after HSCT were analyzed. According to the surgical intervention of hydronephrosis and ureteral dialation of ureteral stricture, the patients were divided into two groups, rank-sum test and exact probability test were used to evaluate whether there were significant differences in the time of hemorrhagic cystitis (HC) occurred, ureteritis and viremia. RESULTS: HC, ureteritis, ureteral stenosis were all the causes of hydronephrosis after HSCT. In this study, 69.6% (16/23) of the patients suffered from HSCT were cured by conservative treatment, 30.4% (7/23) by surgical intervention, and 13.0% (3/23) by insertion DJ stent or nephrostomy.Of the patients [17.4% (4/23)] who suffered ureteral stenosis, 2 were cured after the balloon dialation of ureter, 1 needed DJ tube long-term insertion, and 1 was still followed-up. rank-sum test and exact probability test results showed that the patients who needed surgical intervention might suffer from HC later than other patients, and their incidences of viremia and ureteritis were higher, but the differences between the two groups were not statistically significant (P = 0.524, P = 0.169, and P = 0.124, respectively). The results also showed that the ureteritis incidences of the patients who suffered from ureteral stricture and needed ureteral dialation were higher than that of the other patients, and the difference between the two groups was statistically significant (P = 0.024). The patients who needed ureteral dialation suffered from HC later and their incidences of viremia was higher, but the differences between the two groups were not statistically significant (P = 0.73 and P = 0.27). CONCLUSION: HC, ureteritis and ureteral stenosis may cause hydronephrosis after HSCT. Patients may treated by conservative treatment first. Patients who suffered from HC later, viremia and especially ureteritis should be paid more attention to, and be treated with surgical intervention when necessary. The patients with ureteral stenosis could be treated by ureteral balloon dialation. PMID- 25131470 TI - [Diagnosis and treatment of hydrocephalus-accompanied renal calculi complicated with renal tumor: 5 case reports]. AB - OBJECTIVE: To investigate the diagnosis and treatment of renal pelvic tumor combined with renal urinary calculi and hydronephrosis. METHODS: Five patients with renal pelvic tumor who underwent relief of the upper urinary obstruction were reviewed. RESULTS: One of the cases lost the opportunity of surgical therapy when pelvic tumor was detected at the advanced stage, and the other 4 cases had received surgery and were followed up. CONCLUSION: As pelvic tumor progresses rapidly after the renal blood flow is improved, and renal urinary calculi with hydronephrosis relieved; the patients with renal pelvic tumor need early diagnosis, aggressive treatment and close follow-up. PMID- 25131471 TI - [Percutaneous renal puncture guide by a novel real-time needle-tracking ultrasound system for percutaneous nephrolithotomy: analysis of 16 cases]. AB - OBJECTIVE: To evaluate the feasibility and efficacy of percutaneous renal puncture in percutaneous nephrolithotomy guided by novel needle-tracking ultrasound system. METHODS: From may to october 2013, 16 cases of percutaneous nephrolithotomy were performed under the guidance of ultrasound system. The clinical data including the time of completing percutaneous renal puncture, the color of urine sucked out from the kidney calices, and the complications were analyzed retrospectively. RESULTS: Of the 16 patients, 18 percutaneous renal access were established guided by ultrasound system. All of them were successtul for the first time, and the average time of completing percutaneous renal punctures was (26.90 +/- 11.37) s (15 to 54 s). After the operation, the hemoglobin decreased by (9.56 +/- 5.27)%(1.41% to 24.06%), and no complications occurred except for postoperative fever in 2 case. CONCLUSION: The novel ultrasound system is a safe and effective technique that can reduce the technical difficulty of percutaneous renal puncture in percutaneous nephrolithotomy. PMID- 25131472 TI - [Analysis for risk factors of systemic inflammatory response syndrome after one phase treatment for apyrexic calculous pyonephrosis by percutaneous nephrolithotomy]. AB - OBJECTIVE: To investigate the risk factors of systemic inflammatory response syndrome (SIRS) after one-phase treatment for apyrexic calculous pyonephrosis by percutaneous nephrolithotomy (PCNL). METHODS: Clinical data of consecutive apyrexic calculous pyonephrosis patients who underwent one-stage PCNL from January 2008 to December 2013 were analyzed retrospectively. The data collected included white blood cells in urine analysis before surgery, midstream urine culture, preoperative renal function, using antibiotics time before surgery, operative time, the number of tracts, intraoperative irrigation peak flow, blood transfusion, and stone composition. Chi-square, t test and Logistic regression methods were used for analysis of each factor and SIRS. RESULTS: A total of 182 patients were enrolled in this study and 38 patients developed SIRS (20.88%). There were no statistically significant differences among white blood cells in urine analysis (P = 0.483), urine culture positive (P = 0.136), and struvite (P = 0.324) in terms of the incidence of postoperative SIRS. Multivariate Logistic regression model indicated that risk factors of SIRS for apyrexic calculous pyonephrosis after one-phase PCNL were renal insufficiency (OR = 5.41, 95% CI 1.84 to 22.64, P = 0.014), operative time (OR = 1.01, 95% CI 1.00 to 1.02, P = 0.024), operative tracts (OR = 3.37, 95% CI -1.92 to 32.55, P = 0.077), intraoperative irrigation peak flow >=500 mL/min (OR = 45.87,95% CI 4.39 to 231.68, P = 0.007), and blood transfusion (OR = 5.98, 95% CI 1.12 to 46.66, P = 0.043). The protective factor was antibiotics use for more than 3 days (OR = 0.34, 95% CI -3.92 to 12.55, P = 0.047). CONCLUSION: The incidence of SIRS after one-phase PCNL treatment for apyrexic calculous pyonephrosis was similar to that of other patients. It is relatively safe and reliable to do this. Preoperative antibiotics should be used for more than 3 days before surgery. Careful manipulation is needed to avoid blood transfusion. It is better to shorten the operative time and to reduce multiple tracts operation. Particularly, irrigation peak flow >=500 mL/min should be avoided in the circumstance of bleeding or turbid urine. PMID- 25131473 TI - [Influence of tension-free midurethral sling surgery on sexual function in women with stress urinary incontinence]. AB - OBJECTIVE: To investigate the change of the female patients' sexual function after tension free vaginal tape (TVT) or transobturator suburethral tape (TVT-O) surgery for stress urinary incontinence (SUI). METHODS: Female sexual function index (FSFI) was sent to 66 female patients who underwent a TVT/TVT-O surgery at least 3 months after the operation, to a maximum of 5 years. All The patients were divided into two groups according to different surgical methods, different follow-up intervals (more than or less than 1 year) and whether there was concomitant coital incontinence (CCI) before the operation. The changes of FSFI scores before and after the operation were compared between the two groups by multiple covariances analysis. The total score was higher, and the sexual function was better. RESULTS: In the study, 60 patients answered the questionnaire, and 51 questionnaires were available. Before surgery, there were no significant difference between TVT and TVT-O groups in FSFI, age, body mass index (BMI). As to patients who had TVT/TVT-O surgery, when the influence of the postoperative period and symptoms accompanying intercourse were corrected, the two groups had no significant difference in difference of FSFI (dFSFI) scores after operation (F = 2.52, P = 0.119), and they had similar sexual function improvement ratio (40.0% vs. 44.4%, P > 0.05). But to the patients who had concomitant coital incontinence before the operations, the dFSFI scores was higher than patients who did not have concomitant coital incontinence (1.86 +/- 1.95 vs. -0.09 +/- 2.24, P < 0.05). CONCLUSION: TVT and TVT-O surgery have no significant difference in influence on sexual function in women between each other, but the patients who suffer from CCI before the surgery will have a better sexual function improvement. PMID- 25131474 TI - [Management of female urethral obliteration with the rotary excision appliance]. AB - OBJECTIVE: To describe a new technique using the rotary excision appliance for the treatment of female urethral obliteration and to evaluate the effect of the management. METHODS: Between October 2000 and July 2013, 5 cases of female urethral obstruction (age from 23 to 65 years, time to treatment from 3 to 60 months, obliteraion length from 0.5 to 1.8 cm) were managed using the rotary excision appliance and the patients had been followed up. RESULTS: After a mean of 32.4 months (range: 5 to 75 months) of follow-up, normal micturation had been achieved in all the patients. The maximal urinary flow rate (MFR) ranged from 15 to 28 mL/s (mean 20.6 mL/s). Three patients were continent and 2 patients had slight incontinence. CONCLUSION: The rotary excision appliance is a useful instrument for the management of female urethral obliteration. Our Long-term follow-up provides further support for use of this technique by demonstrating that urethral continuity can be established without increased incidence of stricture formation or incontinence. PMID- 25131475 TI - Chinese urologists' practice patterns of diagnosing and treating chronic pelvic pain syndrome: a questionnaire survey. AB - OBJECTIVE: To investigate the application of the Chinese Urological Association (CUA) guidelines on prostatitis and the effects on the clinical practice patterns of diagnosing and treating chronic pelvic pain syndrome (CPPS) among Chinese urologists. METHODS: We conducted a questionnaire investigation of the CUA guidelines on prostatitis among the urologists from 399 hospitals in 63 cities of China, and performed statistical analyses on all the eligible questionnaires collected. RESULTS: Of the 2 251 questionnaires distributed, 2 046 (90.9%) were eligible, of which 92.5% were from the urologists in tertiary or secondary hospitals, of whom 72.3% had senior or intermediate professional titles, and 90.2% had studied the CUA guidelines. Most respondents agreed that Type III prostatitis was a clinical syndrome, of which the diagnosis should be made after other conditions with similar symptoms had been ruled out and the aim was to relieve pain, alleviate urination symptoms and improve quality of life. Those who had and those who had not studied the CUA guidelines differed in their viewpoints on CPPS as illustrated in the guidelines. In clinical practice, the most common treatment options for CPPS were pharmaceutical therapy (95.0%), life style adjustment (88.9%), and psychotherapy (79.9%), and the most frequently prescribed drugs were phytotherapy (84.5%), alpha-blockers (79.0%) and antibiotics (64.0%). CONCLUSION: CUA guidelines on prostatitis has gained a nationwide application and promoted the standardization of the management of CPPS in China. PMID- 25131476 TI - [Anaplastic lymphoma kinase fusion gene expression, clinical pathological characteristics and prognosis in 95 Chinese patients with non-small cell lung cancer]. AB - OBJECTIVE: To examine the prevalence of anaplastic lymphoma kinase (ALK) fusion gene in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: In this study, 95 patients with NSCLC and corresponding clinical information and formalin-fixed paraffin-embedded (FFPE) tissue blocks were included. Hematoxylin & eosin (HE) staining, conventional ALK immunochemistry (IHC) staining and intercalated antibody-enhanced polymer (iAEP) IHC staining, and dual-color split fluorescence in situ hybridization (FISH) for ALK fusion gene were performed. RESULTS: Eight ALK-positive cases were detected using anti-ALK immunohistochemistry with the iAEP method, and FISH analyses revealed 4 patients of them who harbored the ALK fusion gene (4.2%, 4/95), including 2 cases of female patients with solid signet-ring cell adenocarcinoma and 2 cases of male patients with adenosquamous carcinoma. The positive cases were all non-smokers without EGFR/KRAS mutations. Furthermore, the positive cases all survived, and the overall postsurgery survival time of 2 cases was more than 5 years. CONCLUSION: ALK IHC with the iAEP method is better than conventional ALK IHC, and the percentage of the positive cells is more important than that of the intensity. ALK translocations were infrequent in the entire NSCLC patient population (<5%) with better prognosis. PMID- 25131477 TI - [Relationship of genetic variants and cardiovascular risk factors with interleukin-6 and interleukin-10 secreted by monocytes]. AB - OBJECTIVE: To examine the relationship of interleukin (IL)-6 and IL-10 genetic variants and cardiovascular factors [oxygenized low density lipoprotein (ox-LDL), lower physical activity, overweight, etc.] with IL-6 and IL-10 secreted by monocytes. METHODS: In the study, 40 health persons, aged from 51 to 80 years, without stroke and myocardial infarction, were randomly sampled from a community based population in Beijing in 2010. Their data on smoking, drinking, blood pressure, fasting glucose, and lipid were collected. The single nucleotide polymorphisms (SNPs) of IL-6 (rs1800796, rs1524107, rs2066992) and IL-10 (rs1800872, rs1554286, rs3021094) were genotyped. The human monocytes were cultivated in RPMI 1640 medium for 24 h; then divided into two equal parts, in which ox-LDL (50 mg/L) and phosphate buffer solution (PBS) were added for another 48 h. Finally, the secretions of IL-6 and IL-10 in the culture supernatants were measured with ELISA. RESULTS: Paired Wilcoxon tests showed that the IL-6, IL-10, and IL-6/IL-10 were significantly higher in ox-LDL medium than in PBS one (all P < 0.01). The concentrations in PBS/ox-LDL taken as repeated measurements, and adjusted for age and gender, the repeated general linear models showed: IL-10 was significantly lower for those overweight (BMI >= 26 kg/m(2)) than for those normal weight (P = 0.007), and IL-6/IL-10 was significantly higher in those overweight (P = 0.003). The IL-6/IL-10 was significantly higher in those with lower physical activity [metabolic equivalent of energy, METS < 166 kJ/(kg.d)] than those with higher physical activities (P = 0.046). IL-6 and IL-10 were significantly higher in alcohol drinkers (P = 0.049 and P = 0.006). IL-6 was significantly higher in those with higher high-density lipoprotein-cholesterol (HDL-c, >= 56.4 mg/dL, P = 0.027). There were significant interactions between IL 10 SNPs and ox-LDL on IL-10 (all P < 0.05), but no significant interactions between IL-6 gene SNPs and ox-LDL on IL-6. CONCLUSION: The ox-LDL together with lower physical activity and overweight shifts the balance of pro-inflammatory and anti-inflammatory in the direction of pro-inflammatory. The interaction between IL-10 gene and ox-LDL is intensively correlated with the secretion of the anti inflammatory cytokine IL-10. PMID- 25131478 TI - [Speckle tracking analysis of left atrial phasic function in patients with hypertension]. AB - OBJECTIVE: To assess left atrial (LA) phasic function in hypertension (HT) and to evaluate its relationship with left ventricular diastolic function. METHODS: Cross-sectional data of 738 population (149 non-HT as control, and 589 HT were further grouped into normal left ventricular diastolic function, mild diastolic dysfunction and moderate/severe diastolic dysfunction sub-groups) in an urban community of Beijing were used. LA global longitudinal strain in late diastole (Sa), early diastole (Se), and total strain (Stot = Sa+ Se), strain rate in late diastole (SRa), systole (SRs), and early diastole (SRe) were measured using off line speckle-tracking echocardiography analyzing software, and were compared between non-HT and HT groups, and among HT sub-groups. RESULTS: LA reservoir [Stot: 22.7% +/- 5.9% vs. 21.0% +/- 5.8%, P = 0.002; SRs: (1.1 +/- 0.3)/s vs. (1.0 +/- 0.3)/s, P = 0.033] and conduit [Se: 11.1% +/- 4.8% vs. 9.6% +/- 4.2%, P = 0.001; SRe: (1.0 +/- 0.4)/s vs. (0.9 +/- 0.3)/s, P < 0.001] indexes were reduced significantly in HT, while contraction (Sa & SRa) indexes were similar to those of non-HT. CONCLUSION: LA reservoir and conduit functions are impaired in HT and deteriorate with left ventricular diastolic dysfunction. LA contraction is preserved in HT with normal and mild diastolic dysfunction while impaired in moderate/severe diastolic dysfunction. PMID- 25131479 TI - [Cardioprotective effect and mechanism of intensive lipid modulation on patients with coronary artery disease undergoing noncardiac surgery]. AB - OBJECTIVE: To explore the protective effect and possible mechanism of intensive lipid modulation on the perioperative period of patients with stable coronary artery disease undergoing noncardiac surgery. METHODS: In the study, 60 patients with stable coronary artery disease undergoing elective noncardiac surgery were randomly divided into intensive lipid modulation group (n = 30) and conventional group (n = 30). In intensive lipid modulation group, the patients were given atorvastatin 40 mg every night before surgery, 80 mg 12 h before surgery, and 40 mg 2 h before surgery, and 40 mg every night after noncardiac surgery. In conventional group, the patients were given atorvastatin 20 mg every night before surgery and also after the surgery. The occurrence of perioperative major adverse cardiac events (including sudden cardiac death, acute myocardial infarction, unplanned revascularization) were compared in the two groups. Preoperative and 48 h postoperative changes of lipid levels and inflammatory markers were also compared in the two groups. RESULTS: In conventional group, one patient suffered myocardial infarction with acute anterior ST-segment elevation and was given emergency left anterior descending artery interventional reperfusion therapy, and 7 patients suffered asymptomatic myocardial infarction. In intensive lipid modulation group, one patient suffered asymptomatic myocardial infarction, and the incidence rate of perioperative acute myocardial infarction reduced significantly compared with conventional group (P < 0.05). There was no significant difference in preoperative and postoperative changes of lipid levels in the two groups (P > 0.05), and compared with conventional group, there was significantly lower levels of inflammatory markers in intensive lipid modulation group (P < 0.05). CONCLUSION: The intensive lipid modulation group significantly reduced the incidence of perioperative major adverse cardiac events especially asymptomatic myocardial infarction, and the inhibition of the inflammatory response may be one of the protective mechanisms, which still needs to be further confirmed by large multicenter randomized controlled clinical trials. PMID- 25131480 TI - [Clinical observation of middle cerebral artery angioplasty in treatment of subcortex cerebral watershed infarction with moderate or severe disabilities]. AB - OBJECTIVE: To assess the safety and effectiveness of middle cerebral artery angioplasty in treatment of subcortical watershed infarcts (S-CWI) with moderate or severe disabilities. METHODS: From June 2011 to May 2012, 5 S-CWI patients (six lesions) with moderate or severe disabilities combining severe stenosis in Ipsilateral middle cerebral artery received middle cerebral artery angioplasty in Interventional Radiology and Vascular Surgery Department, Peking University Third Hospital. We observed the neurological score before and after angioplasty and assessed the improvement of neurological functions. RESULTS: The National Institute of Health stroke scale(NIHSS) scores were decreased by 4-6 points and modified Rankin scale(mRs) scores were decreased 1 point in 7 days. In the 3 months' follow-up, 4 patients' mRs scores were 1 point, and 1 patient's was 2 points. In the 1-year follow-up, there were no new strokes and instent restenosis events. CONCLUSION: Middle cerebral artery angioplasty in treatment of S-CWI with moderate or severe disabilities is beneficial. PMID- 25131481 TI - [Controlled clinical study of trigeminal ganglion puncture guided by CT/MRI image fusion interface navigation]. AB - OBJECTIVE: To build the radio-frequency thermocoagulation (RFT) interface under navigation including foramen ovale and trigeminal ganglion based on CT/MRI image fusion technology, to visualize the relationship between the trigeminal ganglion and the puncture needle, and to observe clinical effects of this method. METHODS: CT and MRI data of 20 trigeminal neuralgia patients which were input into BrainLAB-iPlan navigation planning system, were aligned and merged, so that the 3 dimentional image fusion interface of CT and MRI for puncture was built. According to the image fusion interface, the pathways targeting the trigeminal ganglion were planned to assist trigeminal ganglion puncture and RFT. The treatment consequences were observed and compared with 20 patients under the RFT only with the direction of pre- and intra-operative CT. RESULTS: In the group of CT/MRI image fusion cases, 3 cases had been predicted to be difficult because of unreachable ganglion through the foramen ovale pathway. The postoperative clinical examination proved that the ganglions of these 3 cases were only insufficiently damaged or undamaged. The other 17 cases proved better results, except 2 cases whose treatment was changed in operation. The valid rates for both image fusion navigation group and CT group were all above 95%. CONCLUSION: Navigation interface including both foramen ovale and trigeminal ganglion based on CT/MRI image fusion made visualization of the pathway targeting ganglion come true, which made the treatment more accurate and individual. Whether the pathway could reach the ganglion might distinguish the trouble cases from others. PMID- 25131482 TI - [Amplicon density-weighted algorithms for analyzing dissimilarity and dynamic alterations of RAPD polymorphisms of Cordyceps sinensis]. AB - OBJECTIVE: To examine the dynamic maturational alterations of random amplified polymorphic DNA (RAPD) molecular marker polymorphism resulted from differential expressions of multiple fungi in the caterpillar body, stroma and ascocarp portion of Cordyceps sinensis (Cs). METHODS: Used the fuzzy, integral RAPD molecular marker polymorphism method with 20 random primers; used density weighted cluster algorithms and ZUNIX similarity equations; compared RAPD polymorphisms of the caterpillar body, stroma and ascocarp of Cs during maturation; and compared RAPD polymorphisms of Cs and Hirsutella sinensis (Hs). RESULTS: Density-unweighted algorithms neglected the differences in density of the DNA amplicons. Use of the density-weighted ZUNIX similarity equations and the clustering method integrated components of the amplicon density differences in similarity computations and clustering construction and prevented from the loss of the information of fungal genomes. An overall similarity 0.42 (< the overall dissimilarity 0.58) was observed for all compartments of Cs at different maturation stages. The similarities for the stromata or caterpillar bodies of Cs at 3 maturational stages were 0.57 or 0.50, respectively. During Cs maturation, there were dynamic Low->High->Low alterations of the RAPD polymorphisms between stromata and caterpillar bodies dissected from the same pieces of Cs. The polymorphic similarity was the highest (0.87) between the ascocarp and mature stroma, forming a clustering clade, while the premature stroma and caterpillar body formed another clade. These 2 clades merged into one cluster. Another clade containing the maturing stroma and caterpillar body merged with mature caterpillar body, forming another cluster. The RAPD polymorphic similarities between Hs and Cs samples were 0.55-0.69. Hs were separated from Cs clusters by the out-group control Paecilomyces militaris. CONCLUSION: The wealthy RAPD polymorphisms change dynamically in the Cs compartments with maturation. The different RAPD polymorphism for Hs from those for Cs supports the hypothesis of integrated micro-ecosystem Cs with multiple fungi, but does not support the "single fungal species" hypothesis for Cs and the anamorph-teleomorph connection between Hs and Cs. PMID- 25131483 TI - [Preparation and property study of doxorubicin loaded microspheres]. AB - OBJECTIVE: To prepare doxorubicin-loaded polyvinylalcohol-acrylic acid (PVA-AA) microspheres and evaluate properties of this chemoembolic agent. METHODS: PVA-AA microspheres were synthesized by inverse suspension polymerization method and then verified by infrared spectroscopy. drug loading (DL) and entrapment efficiency (EE%) were measured after doxorubicinwas loaded on PVA-AA microspheres. Their morphology and elasticity were investigated by optical microscope, environmental scanning electron microscope and texture analyzer, respectively. T-cell apparatus was used to evaluate the in vitro release behavior of doxorubicin-loaded microspheres.The external carotid of the rabbit was chosen as an embolization site to evaluate the in vivo embolic property of the microspheres. RESULTS: PVA-AA microspheres, which were transparent spheres,turned into red spheres after doxorubicin loading. DL of the microspheres was (20.56 +/- 0.69)g/L and (23.25 +/- 0.27) g/L,and EE% was 82.22% +/- 2.76% and 93.00% +/- 1.06% within 20 min and 6 h, respectively. The in vitro release results showed a significantly delayed release of the drug for 10.32% +/- 0.47% after 24 h. The Young's modulus was (178.30 +/- 12.33) kPa and (213.29 +/- 15.61) kPa for blank microspheres and doxorubicin-loaded microspheres, respectively. Both blank microspheres and doxorubicin-loaded microspheres exhibited good elasticity. In vivo embolization showed that 0.3 mL of microspheres could produce distal embolic efficiency. CONCLUSION: The doxorubicin-loaded microspheres are expected to be a promising new chemoembolic agent. PMID- 25131484 TI - [A prospective randomized control study: new rigid cystoscopy technology to improve patients' comfort]. AB - OBJECTIVE: To determine whether the extruded irrigation solution bag during passage of rigid cystoscope will reduce the patient's discomfort. METHODS: In the study, 378 male patients undergoing rigid cystoscopies were randomized into "Institute of Urology Peking University (IUPU)" technique group (n = 193) and routine manipulation group (n = 185). All the patients had received 10 mL oxybuprocaine gel before manipulation. In the IUPU technique group, irrigation solution bag was connected with cystoscope sheath and obturator. As the scope passed through the bulbar urethra, a nurse was instructed to extrude the irrigating fluid bag. A 10-point visual analog pain scale assessment was completed by the patient after the procedure. RESULTS: The visual analog pain score was 2 (1-2) in the IUPU technique group and 4 (3-6) in the routine manipulation group (P < 0.001, Mann-Whitney U test). All the procedure indications had no effect on the findings. CONCLUSION: This study has shown that a simple IUPU technique can significantly reduce the patient's discomfort during outpatient rigid cystoscopy. We strongly recommend this technique for all male patients undergoing rigid cystoscopy. PMID- 25131485 TI - [Transabdominal laparoscopic radical nephrectomy of modified Pfannenstiel incision]. AB - OBJECTIVE: To evaluate the efficacy and safety of transperitoneal laparoscopic radical nephrectomy with the modified Pfannenstiel incision. METHODS: Between Aug. 2012 and Jul. 2013, the same surgeon performed transperitoneal laparoscopic radical nephrectomy for 12 patients with renal masses. The approach was usually performed through 3 ports or 4 ports placed in a traditional manner. After laparoscopic radical nephrectomy was completed, and the specimen was entrapped in a specimen retrieval bag, a 7 cm modified Pfannenstiel skin incision was made over the symphysis pubis, lateralized slightly toward the side of surgery. RESULTS: All the procedures were completed without conversion to open radical nephrectomy. The operative time was 106 to 234 minutes and the blood loss was minimal. There was no intra- or post-operative complications. The pathological result was renal cell carcinoma. One patient died of multiple organ metastasis after 5 months. No recurrence was seen after 9 to 20 months' follow-up. CONCLUSION: Laparoscopic radical nephrectomy with the modified Pfannenstiel incision where the kidney is removed offers the benefits of improved cosmesis over the traditional muscle-cutting extension of an upper abdominal, lateral port site. The modified Pfannenstiel incision combines the advantages of a low abdominal incision and improved cosmesis, and can be considered a potential alternative for traditional laparoscopic nephrectomy. PMID- 25131486 TI - [Micropump infusion of gonadorelin in the treatment of hypogonadotropic hypogonadism in patients with pituitary stalk interruption syndrome: cases analysis and literature review]. AB - Two cases of hypogonadotropic hypogonadism caused by pituitary stalk interruption syndrome treated by pulse infusion of gonadorelin via micropump were reported, and their clinical features and the treatment process of pulse infusion of gonadorelin via micropump summarized. Both of the 2 patients were presented primarily with hypogonadotropic hypogonadism. After the treatment with pulse infusion of gonadorelin via micropump, their syndrome of androgen deficiency improved and the gonadotropin levels promoted at the end of 12 weeks' follow-up. Pulse infusion of gonadorelin via micropump is an alternative to treat hypogonadotropic hypogonadism caused by pituitary stalk interruption syndrome. PMID- 25131487 TI - [Leucine-rich glioma inactivated-1 protein antibody associated limbic encephalitis: one case report]. AB - OBJECTIVE: To report a case of leucine-rich glioma inactivated-1 protein antibody (LGI1-Ab) associated limbic encephalitis. METHODS: A 76-year-old woman was admitted to the hospital because of cognitive impairment and faciobrachial dystonic seizures for six months. Hyponatremia was also noted in this patient. Antibodies to the LGI1 were positive.(18)F-FDG uptake was measured on the PET-CT scans of this patient. RESULTS: PET-CT showed bilateral putamen hypermetabolism with hypometabolism in other regions. Her symptoms were improved after intravenous immunoglobulin therapy. CONCLUSION: LGI1-Ab associated encephalitis can manifest as basal ganglia hypermetabolism and faciobrachial dystonic seizures. PMID- 25131488 TI - [Retroperitoneal laparoscopic partial nephrectomy for treatment of cystic nephroma: one case report]. AB - The clinical features and pathologic findings of one case of cystic nephroma was reported,and the safety of treatment by retroperitoneal laparoscopic partial nephrectomy evaluated. The patient was a 20-year-old woman, and found left renal cyst for 1 year with pain in her left flank one month ago. The patient was diagnosed as complex renal cyst, then underwent retroperitoneal laparoscopic partial nephrectomy. In the operation, the tumor was located in the middle and lower part of her left kidney, with a number of small sample masses, and a solid mass near the renal parenchymal part. The operation time was 224 min, and the artery occlusion time was about 17 min. The blood loss was 20 mL, with no blood transfusion. The pathology was cystic nephroma. No operation complication was seen, nor was recurrence after a short-term follow-up. Cystic nephroma is a relatively rare benign lesion of the kidney. Retroperitoneal laparoscopic partial nephrectomy is a safe and effective way to treat cystic nephroma. PMID- 25131489 TI - [Use of abiraterone acetate in the treatment of patients with metastatic castration resistant prostate cancer and no prior chemotherapy: 3 case reports and literature review]. AB - OBJECTIVE: To evaluate the safety and efficiency of using abiraterone and prednisone in the treatment of patient with metastatic castration resistant prostate cancer (mCRPC) no prior chemotherapy. METHODS: Three mCRPC no prior chemotherapy patients accepted abiraterone and prednisone treatment. The clinical data were analyzed retrospectively and the safety and efficiency of this treatment option were discussed. The Gleason scores of the three mCRPC patients were 5, 9, and 9. The clinical stages were T3aNxM0, T3aNxM1b, and T3aNxM1b. The patients received abiraterone 1 000 mg daily and prednisone 5 mg twice daily and androgen deprivation therapy in the treatment. Their blood pressure, complete blood count, prostate specific antigen (PSA), biochemical parameters, whole body CT scan and bone scan were done regularly to monitor the progression of the diseases. RESULTS: In this study, the general condition improved in two patients. Two of the three patients experienced decrease of PSA and no progression. One patient experienced disease progression. Generally, abiraterone and prednisone resulted in prolonged radiographic progression-free survival and delayed in PSA progression in mCRPC no prior chemotherapy. There were no severe side effects, such as hypokalemia, hypertension, and water-sodium retention. The patient's tolerance was good. CONCLUSION: Abiraterone and prednisone are safe and can improve mCRPC no prior chemotherapy patient's life quality and may prolong the overall survival. PMID- 25131490 TI - [Balloon dilation by B ultrasound monitoring for treatment of urethral stricture: 5 case reports]. AB - Urethral stricture is a common urologic disease and there are many therapeutic methods for it. Here we investigated the application of balloon dilation under B mold ultrasound monitoring in the treatment of urethral stricture. Five male patients suffering from urethral stricture were treated with balloon dilation under B-mold ultrasound monitoring.Their urination was assessed after operation. All the patients underwent the operation successfully, without serious complications. The urinary catheter was removed 3-4 weeks after operation. The patients were followed up for 8 to 15 months. Four patients were voiding well and one improved. Balloon dilation under B-mold ultrasound monitoring in the treatment of urethral stricture was intuitive, safe and effective. PMID- 25131491 TI - [Paroxysmal kinesigenic dyskinesia: 2 case reports]. AB - Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological condition in which brief and frequent dyskinetic attacks are provoked by sudden movement. PKD is more common in men and can be idiopathic (commonly familial) or due to a variety of causes. The pathophysiology of PKD is uncertain but it could be an ion-channel disorder. Genetic linkage studies have isolated several loci on chromosome 16, and proline-rich transmembrane protein 2 (PRRT2) has been identified as a causative gene of PKD by using a combination of exome sequencing and linkage analysis. Antiepileptic drugs, particularly, carbamazepine are very helpful in a large proportion of cases. Sometimes it can be difficult to distinguish this syndrome from epilepsy. We reported 2 patients who presented abnormal involuntary attack. Evaluations included general physical examinations, endocrinologic and metabolic studies, video electroencephalograms and brain MRI imaging. All of these studies were normal. All of symptoms showed excellent response to carbamazepine. PMID- 25131492 TI - Sensitive determination of carbidopa through the electrochemiluminescence of luminol at graphene-modified electrodes. AB - Using the concept of electrogenerated chemiluminescence (ECL), a sensitive analytical method for the determination of carbidopa is described. Electro oxidation of carbidopa on the surface of a graphene oxide (GO)-modified gold electrode (GE) leads to enhancement of the weak emission of oxidized luminol. Under optimum experimental conditions, the ECL signal increases linearly with increasing carbidopa concentrations over a range of 1.0 * 10(-9) -1.7 * 10(-7) M, with a detection limit of 7.4 * 10(-10) M. The proposed ECL method was successfully used for the determination of carbidopa in urine samples. PMID- 25131493 TI - Significant factors in family difficulties for fathers and mothers who use support services for children with hikikomori. AB - AIMS: Hikikomori is a new psychosociological phenomenon among youth, of almost complete withdrawal from social interaction, and it has received considerable attention in community mental health in Japan. The aims of the present study were to identify the influential factors of family difficulties of parents who use support services for children with hikikomori, and compare them between fathers and mothers. METHODS: Data were collected from 110 parents (55 couples) of children with hikikomori with regard to family difficulties, quality of life, and depression variables via self-report questionnaires. To assess the influential factors of Family Difficulties for parents with children with hikikomori, hierarchical multiple linear regression analysis was carried out for gender. RESULTS: While 94.5% of mothers received some kind of family support, only 61.9% of fathers received it. For both genders, the number of services that the fathers received was significantly correlated with marital cooperation, and the number of services that the mothers received was significantly correlated with support resource utilization. CONCLUSIONS: It is necessary for fathers to receive more support, and it is important for professionals to encourage parents to address their difficulties together. PMID- 25131494 TI - The role of influenza in the severity and transmission of respiratory bacterial disease. AB - Infections with influenza viruses and respiratory bacteria each contribute substantially to the global burden of morbidity and mortality. Simultaneous or sequential infection with these pathogens manifests in complex and difficult-to treat disease processes that need extensive antimicrobial therapy and cause substantial excess mortality, particularly during annual influenza seasons and pandemics. At the host level, influenza viruses prime respiratory mucosal surfaces for excess bacterial acquisition and this supports increased carriage density and dissemination to the lower respiratory tract, while greatly constraining innate and adaptive antibacterial defences. Driven by virus-mediated structural modifications, aberrant immunological responses to sequential infection, and excessive immunopathological responses, co-infections are noted by short-term and long-term departures from immune homoeostasis, inhibition of appropriate pathogen recognition, loss of tolerance to tissue damage, and general increases in susceptibility to severe bacterial disease. At the population level, these effects translate into increased horizontal bacterial transmission and excess use of antimicrobial therapies. With increasing concerns about future possible influenza pandemics, the past decade has seen rapid advances in our understanding of these interactions. In this Review, we discuss the epidemiological and clinical importance of influenza and respiratory bacterial co infections, including the foundational efforts that laid the groundwork for today's investigations, and detail the most important and current advances in our understanding of the structural and immunological mechanisms underlying the pathogenesis of co-infection. We describe and interpret what is known in sequence, from transmission and phenotypic shifts in bacterial dynamics to the immunological, cellular, and molecular modifications that underlie these processes, and propose avenues of further research that might be most valuable for prevention and treatment strategies to best mitigate excess disease during future influenza pandemics. PMID- 25131495 TI - Development and validation of a microRNA based diagnostic assay for primary tumor site classification of liver core biopsies. AB - Identification of the primary tumor site in patients with metastatic cancer is clinically important, but remains a challenge. Hence, efforts have been made towards establishing new diagnostic tools. Molecular profiling is a promising diagnostic approach, but tissue heterogeneity and inadequacy may negatively affect the accuracy and usability of molecular classifiers. We have developed and validated a microRNA-based classifier, which predicts the primary tumor site of liver biopsies, containing a limited number of tumor cells. Concurrently we explored the influence of surrounding normal tissue on classification. MicroRNA profiling was performed using quantitative Real-Time PCR on formalin-fixed paraffin-embedded samples. 278 primary tumors and liver metastases, representing nine primary tumor classes, as well as normal liver samples were used as a training set. A statistical model was applied to adjust for normal liver tissue contamination. Performance was estimated by cross-validation, followed by independent validation on 55 liver core biopsies with a tumor content as low as 10%. A microRNA classifier developed, using the statistical contamination model, showed an overall classification accuracy of 74.5% upon independent validation. Two-thirds of the samples were classified with high-confidence, with an accuracy of 92% on high-confidence predictions. A classifier trained without adjusting for liver tissue contamination, showed a classification accuracy of 38.2%. Our results indicate that surrounding normal tissue from the biopsy site may critically influence molecular classification. A significant improvement in classification accuracy was obtained when the influence of normal tissue was limited by application of a statistical contamination model. PMID- 25131499 TI - Prevalence and risk factors for diabetic retinopathy in the 40 to 80 year-old population in Yazd, Iran: the Yazd Eye Study. PMID- 25131496 TI - Acid ceramidase is associated with an improved prognosis in both DCIS and invasive breast cancer. AB - Acid ceramidase (ASAH1) a key enzyme of sphingolipid metabolism converting pro apoptotic ceramide to sphingosine has been shown to be overexpressed in various cancers. We previously demonstrated higher expression of ASAH1 in ER positive compared to ER negative breast cancer. In the current study we performed subtype specific analyses of ASAH1 gene expression in invasive and non invasive breast cancer. We show that expression of ASAH1 is mainly associated with luminal A - like cancers which are known to have the best prognosis of all breast cancer subtypes. Moreover tumors with high ASAH1 expression among the other subtypes are also characterized by an improved prognosis. The good prognosis of tumors with high ASAH1 is independent of the type of adjuvant treatment in breast cancer and is also detected in non small cell lung cancer patients. Moreover, even in pre invasive DCIS of the breast ASAH1 is associated with a luminal phenotype and a reduced frequency of recurrences. Thus, high ASAH1 expression is generally associated with an improved prognosis in invasive breast cancer independent of adjuvant treatment and could also be valuable as prognostic factor for pre invasive DCIS. PMID- 25131498 TI - Having a direct look: analysis of DNA damage and repair mechanisms by next generation sequencing. AB - Genetic information is under constant attack from endogenous and exogenous sources, and the use of model organisms has provided important frameworks to understand how genome stability is maintained and how various DNA lesions are repaired. The advance of high throughput next generation sequencing (NGS) provides new inroads for investigating mechanisms needed for genome maintenance. These emerging studies, which aim to link genetic toxicology and mechanistic analyses of DNA repair processes in vivo, rely on defining mutational signatures caused by faulty replication, endogenous DNA damaging metabolites, or exogenously applied genotoxins; the analysis of their nature, their frequency and distribution. In contrast to classical studies, where DNA repair deficiency is assessed by reduced cellular survival, the localization of DNA repair factors and their interdependence as well as limited analysis of single locus reporter assays, NGS based approaches reveal the direct, quantal imprint of mutagenesis genome-wide, at the DNA sequence level. As we will show, such investigations require the analysis of DNA derived from single genotoxin treated cells, or DNA from cell populations regularly passaged through single cell bottlenecks when naturally occurring mutation accumulation is investigated. We will argue that the life cycle of the nematode Caenorhabditis elegans, its genetic malleability combined with whole genome sequencing provides an exciting model system to conduct such analysis. PMID- 25131501 TI - WITHDRAWN: Who are the patients with extrapulmonary tuberculosis? AB - This article has been withdrawn for editorial reasons because the journal will be published only in English. In order to avoid duplicated records, this article can be found at http://dx.doi.org/10.1016/j.rppnen.2014.06.010. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 25131500 TI - Sirtuin inhibitor Ex-527 causes neural tube defects, ventral edema formations, and gastrointestinal malformations in Xenopus laevis embryos. AB - Chemical reagent Ex-527 is widely used as a major inhibitor of Sirtuin enzymes, which are a family of highly conserved protein deacetylases and have been linked with caloric restriction and aging by modulating energy metabolism, genomic stability, and stress resistance. However, the extent to which Ex-527 controls early developmental events of vertebrate embryos remains to be understood. Here, we report an examination of Ex-527 effects during Xenopus early development, followed by a confirmation of expressions of xSirt1 and xSirt2 in embryonic stages and enhancement of acetylation by Ex-527. First, we found that reductions in size of neural plate at neurula stages were induced by Ex-527 treatment. Second, tadpoles with short body length and large edematous swellings in the ventral side were frequently observed. Moreover, Ex-527-treated embryos showed severe gastrointestinal malformations in late tadpole stages. Taken together with these results, we conclude that the Sirtuin family start functioning at early embryonic stages and is required for various developmental events. PMID- 25131502 TI - WITHDRAWN: Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways. AB - This article has been withdrawn for editorial reasons because the journal will be published only in English. In order to avoid duplicated records, this article can be found at http://dx.doi.org/10.1016/j.rppnen.2014.05.006. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 25131503 TI - A case for the use of autoethnography in nursing research. AB - AIMS: This paper discusses the basis for and potential usefulness of autoethnography as a research method in nursing. BACKGROUND: While qualitative research in nursing has traditionally involved the researcher taking an objective stance, autoethnography, with roots in the social sciences, is an emerging method that examines the researcher's own experience in a cultural context. DESIGN: Discussion paper. DATA SOURCES: Data sources from 1979-2013 in the CINAHL, Medline and PsycInfo databases were drawn on including articles from nursing and social science journals on autoethnography and related narrative-based approaches. DISCUSSION: Autoethnography is based on the assumption that reality is multifaceted and the role of culture and context is crucial in understanding human experience. The reader is engaged through the evocation of emotion and the stimulation of reflection. IMPLICATIONS FOR NURSING: While autoethnography has thus far been little used in the discipline of nursing, it is a methodology that offers novel insights and an opportunity to examine the impact of nurses' personal and professional cultural identity on their practice. CONCLUSION: Through the use of a subjective lens, autoethnography gives nurses the opportunity to tell stories that would otherwise not be heard. It involves a courageous laying bare of the self to gain new cultural understandings and it offers the potential for nurses to learn from the experiences and reflections of other nurses. PMID- 25131504 TI - Reported side effects of intravenous midazolam sedation when used in paediatric dentistry: a review. AB - BACKGROUND: Intravenous (IV) midazolam may be of value as an alternative paediatric dental sedation technique, but there is some apprehension concerning its routine use due to a lack of evidence regarding its safety and side effects. AIM: To review all available literature reporting the side effects of IV midazolam in children undergoing dental procedures. DESIGN: Both randomised controlled trials (RCT) and non-randomised studies were reviewed. Reported side effects were categorised as either significant or minor, and the percentage prevalence of significant or minor side effects per episode of treatment was calculated. RESULTS: Five RCTs were included, in which no significant side events were reported; however, minor side effects were recorded (n = 33, 19.5%), with paradoxical reaction being the most common (n = 11, 6.5%). Six non-randomised studies were included, in which no significant side effects were reported; however, minor side effects were reported (n = 118, 16.8%) with paradoxical reaction being the most common (n = 89, 12.7%). CONCLUSIONS: Although no significant side effects were recorded, of the minor side effects reported paradoxical reaction was the most common. Due to inconsistency in side effect reporting, the authors suggest the application of a standardised adverse event reporting tool for future studies of sedation in paediatric dentistry. PMID- 25131505 TI - Daytime light exposure: effects on biomarkers, measures of alertness, and performance. AB - Light can elicit an alerting response in humans, independent from acute melatonin suppression. Recent studies have shown that red light significantly increases daytime and nighttime alertness. The main goal of the present study was to further investigate the effects of daytime light exposure on performance, biomarkers and measures of alertness. It was hypothesized that, compared to remaining in dim light, daytime exposure to narrowband long-wavelength (red) light or polychromatic (2568K) light would induce greater alertness and shorter response times. Thirteen subjects experienced three lighting conditions: dim light (<5lux), red light (lambdamax=631nm, 213lux, 1.1W/m(2)), and white light (2568K, 361lux, 1.1W/m(2)). The presentation order of the lighting conditions was counterbalanced across the participants and each participant saw a different lighting condition each week. Our results demonstrate, for the first time, that red light can increase short-term performance as shown by the significant (p<0.05) reduced response time and higher throughput in performance tests during the daytime. There was a significant decrease (p<0.05) in alpha power and alpha theta power after exposure to the white light, but this alerting effect did not translate to better performance. Alpha power was significantly reduced after red light exposure in the middle of the afternoon. There was no significant effect of light on cortisol and alpha amylase. The present results suggest that red light can be used to increase daytime performance. PMID- 25131506 TI - The effects of curcumin on depressive-like behavior in mice after lipopolysaccharide administration. AB - Current evidence supports that inflammation and increased cytokine levels are associated with depression-like symptoms and neuropsychological disturbances in humans. Curcumin has anti-inflammatory, antioxidant and anti-depressant-like properties. Here, we examined the effects of curcumin on lipopolysaccharide (LPS) induced depressive-like behavior and inflammation in male mice. A single administration of LPS (0.83mg/kg, i.p.) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), reduced sucrose consumption without affecting spontaneous locomotor activity. Pretreatment with curcumin (50mg/kg, i.p.) for 7 consecutive days reversed LPS-induced alterations in the FST, TST, and sucrose preference test. Moreover, pre-treatment with curcumin attenuated LPS-induced microglial activation and overproduction of pro inflammatory cytokine (interleukin-1beta and tumor necrosis factor-alpha), as well as the levels of inducible nitric oxide synthase and cyclooxygenase-2 mRNA in the hippocampus and prefrontal cortex (PFC). In addition, curcumin ameliorated LPS-induced NF-kappaB activation in the hippocampus and PFC. The results demonstrate that curcumin may be an effective therapeutic agent for LPS-induced depressive-like behavior, partially due to its anti-inflammatory aptitude. PMID- 25131508 TI - Treats: low socioeconomic status Australian parents' provision of extra foods for their overweight or obese children. AB - ISSUE ADDRESSED: Child obesity is a global issue, with rates highest among disadvantaged groups. Overconsumption of treats is a contributor to children's weight problems. The objective of this study was to explore low socioeconomic parents' beliefs and behaviours relating to their provision of treat foods for their overweight or obese children. METHODS: Qualitative methods were used to collect data; these included introspections, interviews and focus groups. A total of 37 parents of overweight or obese children aged between 5 and 9 years took part in the 12-month study. RESULTS: Most parents provided their children with treats on a daily basis. Factors affecting parents' provision of treats included parents' desire to control their children's behaviour, to demonstrate love and affection, and to address deprivation beliefs. CONCLUSION: There is considerable scope for improving these parents' treating behaviours by understanding the relevant factors underpinning their situations and choices. SO WHAT? The findings provide an indication of the kinds of health promotion interventions that may be needed to assist in addressing treating behaviours among disadvantaged parents with overweight or obese children. PMID- 25131510 TI - Experimental and theoretical confirmation of the scaling exponent 2 in pyramidal load displacement data for depth sensing indentation. AB - A series of articles by Kaupp et al. have recently been published in "Scanning," containing erroneous claims about the curvature of pyramidal nanoindentation loading curves. The present paper recalls the theoretical reasons why, for self similar indenter shapes like pyramidal or conical indentations, the load scales with the indentation depth squared. Furthermore, experimental evidence for that behavior is provided for a wide variety of materials, ranging from ceramics to metals and polymers. PMID- 25131509 TI - Liver sinusoidal endothelial cells in hepatic fibrosis. AB - Capillarization, lack of liver sinusoidal endothelial cell (LSEC) fenestration, and formation of an organized basement membrane not only precedes fibrosis, but is also permissive for hepatic stellate cell activation and fibrosis. Thus, dysregulation of the LSEC phenotype is a critical step in the fibrotic process. Both a vascular endothelial growth factor (VEGF)-stimulated, nitric oxide (NO) independent pathway and a VEGF-stimulated NO-dependent pathway are necessary to maintain the differentiated LSEC phenotype. The NO-dependent pathway is impaired in capillarization and activation of this pathway downstream from NO restores LSEC differentiation in vivo. Restoration of LSEC differentiation in vivo promotes HSC quiescence, enhances regression of fibrosis, and prevents progression of cirrhosis. PMID- 25131511 TI - Controlled silica deposition on self-assembled peptide nanostructures via varying molecular structures of short amphiphilic peptides. AB - Cationic amphiphilic peptides are highly similar to native silaffins and silicateins for biosilicification in terms of their composition, amphiphilicity, and self-assembling propensity. To understand the relationship between organic molecular structures, molecular self-assembly and silica morphogenesis during biosilicification, we have prepared a series of short self-assembling peptide amphiphiles (I3-5K, I4K2, I3-4R, and I4R2) and investigated their capability to mediate silicification under ambient conditions. I3K self-assembled into tubular nanofibrils while I4K1-2 and I5K formed solid nanofibrils in aqueous solution with their outer diameters decreasing as the number of hydrophobic or hydrophilic amino acid residues increased. Changes in molecular structure thus altered their self-assembled geometries, and the exposed surfaces and surface lysine densities under different geometries then played different mediating roles in silicification, leading to different silica deposition patterns and final silica nanostructures. The templating capacity was weakened or lost when lysine was replaced by arginine, despite the fact that I3-4R and I4R2 self-assembled into nanofibrils and nanoribbons under similar conditions. PMID- 25131512 TI - Duration of obesity and overweight and risk of type 2 diabetes among US women. AB - OBJECTIVE: The purpose of this study was to examine the association between duration of adiposity and risk of type 2 diabetes (T2D) in US women. METHODS: Nearly 61,821 participants were prospectively followed from the Nurses' Health Study (1984-2008) and 63,653 participants from Nurses' Health Study II (1991 2011). Participants were considered overweight (BMI 25-30 kg m(-2) ) or obese (BMI >= 30 kg m(-2) ) if their BMI was above the cutoffs for two successive assessments. The time-dependent Cox proportional hazard models were used to assess associations between excess weight duration and T2D risk. RESULTS: In pooled multivariable analyses of the two cohorts, each two extra years of being overweight was associated with 9% (RR = 1.09, 95% CI 1.08-1.09) increased risk of developing T2D. For each 2-year increment in obesity duration, the risk of T2D was increased by 14% (RR = 1.14, 95% CI 1.14-1.15). Adjustment for current BMI greatly attenuated the association for obesity duration (RR = 1.02, 95% CI 1.01 1.03), although the attenuation was less for overweight duration (RR = 1.04, 95% CI 1.04-1.05). CONCLUSIONS: Both overweight and obesity duration were associated with a significantly higher risk of T2D, and these associations were mainly explained by current BMI, especially for obesity duration. PMID- 25131513 TI - The effect of ZnCl2 on green Spanish-style table olive packaging, a presentation style dependent behaviour. AB - BACKGROUND: Zinc chloride has been used previously as a preservative in directly brined olives with promising results. However, this is the first time that the effects of ZnCl2 addition (0-1 g L(-1) ) on green Spanish-style table olive (cv. Manzanilla) packaging has been studied. RESULTS: The presence of ZnCl2 affected the physico-chemical characteristics of the products; the presence of the Zn led to lower pH values (particularly just after packaging) and titratable and combined acidity values than the control but did not produce clear trends in the colour parameters. No Enterobacteriaceae were found in any of the treatments evaluated. At the highest ZnCl2 concentrations, the lactic acid bacteria were inhibited while, unexpectedly, its presence showed a lower effect than potassium sorbate against the yeast population. Regardless of the use of potassium sorbate or ZnCl2 , the packages had a reduced microbial biodiversity because only Lactobacillus pentosus and Pichia galeiformis were found at the end of the shelf life. With respect to organoleptic characteristics, the presentations containing ZnCl2 were not differentiated from the traditional product. CONCLUSION: Zinc chloride was less efficient than potassium sorbate as a yeast inhibitor in green Spanish-style olives, showing clear presentation style dependent behaviour for this property. Its presence produced significant changes in chemical parameters but scarcely affected colour or sensory characteristics. PMID- 25131514 TI - The amnion muscle combined graft (AMCG) conduits: a new alternative in the repair of wide substance loss of peripheral nerves. AB - The use of autologous sural nerve grafts is still the current gold standard for the repair of peripheral nerve injuries with wide substance losses, but with a poor rate of functional recovery after repair of mixed and motor nerves, a limited donor nerve supply, and morbidity of donor site. At present, tubulization through the muscle vein combined graft, is a viable alternative to the nerve autografts and certainly is a matter of tissue engineering still open to continuous development, although this technique is currently limited to a critical gap of 3 cm with less favorable results for motor function recovery. In this report, we present a completely new tubulization method, the amnion muscle combined graft (AMCG) technique, that consists in the combination of the human amniotic membrane hollow conduit with autologous skeletal muscle fragments for repairing the substance loss of peripheral nerves and recover both sensory and motor functions. In a series of five patients with loss of substance of the median nerve ranging 3-5 cm at the wrist, excellent results graded as S4 in two cases, S3+ in two cases, and S3 in one case; M4 in four cases and M3 in one case were achieved. No iatrogenic damage due to withdrawal of a healthy nerve from donor site was observed. This technique allows to repair extensive loss of substance up to 5 cm with a good sensory and motor recovery. The AMCG thus may be considered a reasonable alternative to traditional nerve autograft in selected clinical conditions. PMID- 25131515 TI - Is evaluative conditioning really resistant to extinction? Evidence for changes in evaluative judgements without changes in evaluative representations. AB - Evaluative conditioning (EC) is defined as the change in the evaluation of a conditioned stimulus (CS) due to its pairing with a positive or negative unconditioned stimulus (US). Although several individual studies suggest that EC is unaffected by unreinforced presentations of the CS without the US, a recent meta-analysis indicates that EC effects are less pronounced for post-extinction measurements than post-acquisition measurements. The disparity in research findings suggests that extinction of EC may depend on yet unidentified conditions. In an attempt to uncover these conditions, three experiments (N = 784) investigated the influence of unreinforced post-acquisition CS presentations on EC effects resulting from simultaneous versus sequential pairings and pairings with single versus multiple USs. For all four types of CS-US pairings, EC effects on self-reported evaluations were reduced by unreinforced CS presentations, but only when the CSs had been rated after the initial presentation of CS-US pairings. EC effects on an evaluative priming measure remained unaffected by unreinforced CS presentations regardless of whether the CSs had been rated after acquisition. The results suggest that reduced EC effects resulting from unreinforced CS presentations are due to judgement-related processes during the verbal expression of CS evaluations rather than genuine changes in the underlying evaluative representations. PMID- 25131507 TI - Regulation of object recognition and object placement by ovarian sex steroid hormones. AB - The ovarian hormones 17beta-estradiol (E2) and progesterone (P4) are potent modulators of hippocampal memory formation. Both hormones have been demonstrated to enhance hippocampal memory by regulating the cellular and molecular mechanisms thought to underlie memory formation. Behavioral neuroendocrinologists have increasingly used the object recognition and object placement (object location) tasks to investigate the role of E2 and P4 in regulating hippocampal memory formation in rodents. These one-trial learning tasks are ideal for studying acute effects of hormone treatments on different phases of memory because they can be administered during acquisition (pre-training), consolidation (post-training), or retrieval (pre-testing). This review synthesizes the rodent literature testing the effects of E2 and P4 on object recognition (OR) and object placement (OP), and the molecular mechanisms in the hippocampus supporting memory formation in these tasks. Some general trends emerge from the data. Among gonadally intact females, object memory tends to be best when E2 and P4 levels are elevated during the estrous cycle, pregnancy, and in middle age. In ovariectomized females, E2 given before or immediately after testing generally enhances OR and OP in young and middle-aged rats and mice, although effects are mixed in aged rodents. Effects of E2 treatment on OR and OP memory consolidation can be mediated by both classical estrogen receptors (ERalpha and ERbeta), and depend on glutamate receptors (NMDA, mGluR1) and activation of numerous cell signaling cascades (e.g., ERK, PI3K/Akt, mTOR) and epigenetic processes (e.g., histone acetylation, DNA methylation). Acute P4 treatment given immediately after training also enhances OR and OP in young and middle-aged ovariectomized females by activating similar cell signaling pathways as E2 (e.g., ERK, mTOR). The few studies that have administered both hormones in combination suggest that treatment can enhance OR and OP, but that effects are highly dependent on factors such as dose and timing of administration. In addition to providing more detail on these general conclusions, this review will discuss directions for future avenues of research into the hormonal regulation of object memory. PMID- 25131517 TI - A review of the relationship between the needs of mothers who have hearing impairment children and their state-trait anxiety levels. AB - This descriptive research was carried out to identify the relationship between the needs of those mothers who have hearing impairment children and their state/trait anxiety levels. Significant positive relationships were found between the mothers' state anxiety level and the overall FNS score, the subscales of Need for Information, Help Explaining to Others, Community Services, Financial Assistance and Family Functioning and also significant positive relationship were found between the trait anxiety level and the overall FNS score, the subscales of Need for Information, Need for Support, Help Explaining to Others Community Services, Financial Assistance and Family Functioning. PMID- 25131518 TI - Geography and the burden of care in pediatric cancers. AB - BACKGROUND: Childhood cancers typically require rigorous treatment at specialized centers in urban areas, which can create substantial challenges for families residing in remote communities. We evaluated the impact of residence and travel time on the burden of care for families of childhood cancer patients. PROCEDURE: We conducted a cross-sectional, self-administered survey of 354 caregivers of pediatric cancer patients at a children's hospital serving a seven state area. Measures included the impact of cancer treatment on relocation, employment, schooling, and finances. We evaluated these domains by rural/urban residence and travel time (>1 hour and >2 hours) to the hospital in multivariable regression models. RESULTS: Of the 29% of caregivers who reported moving residences as their child was diagnosed, 33% reported that the move was due to their child's cancer. Rural and remote (e.g., >1 hour travel time) caregivers missed more days of work during the first month after diagnosis than did urban and local caregivers, however, these differences did not persist over the first 6 months of therapy. One-third of caregivers reported quitting or changing jobs as a direct result of their child being diagnosed with cancer. Rural respondents had greater out-of pocket travel expenses and reported a significantly greater perceived financial burden. Rural patients missed more school days and were at an increased risk of having to repeat a grade. CONCLUSIONS: Childhood cancer has an appreciable impact on the lives of patients and caregivers. The burden is greater for those living far from a treatment center. PMID- 25131519 TI - Clinical and neuropsychological characteristics of euthymic bipolar patients having a history of severe suicide attempt. AB - OBJECTIVE: Identifying bipolar patients at high-suicide risk is a major health issue. To improve their identification, we compared dimensional and neuropsychological profile of bipolar patients with or without history of suicide attempt, taking into account suicidal severity (i.e. admission to intensive ward). METHOD: A total of 343 adult euthymic bipolar out-patients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into three subgroups: 214 patients without history of suicide attempt, 88 patients with past history of non-severe suicide attempt and 41 patients with past history of severe suicide attempt. General intellectual functioning, speed of information processing, verbal learning and memory, verbal fluency and executive functioning were assessed. RESULTS: Severe suicide attempters had lower affective intensity and lability than non-severe attempters. Severe suicide attempters outperformed non-severe attempters for verbal learning and non attempters for Stroop word reading part after adjustment for study centre, age, gender, educational level, antipsychotics use, depression score, anxious and addictive comorbidities. CONCLUSION: Neuropsychological tasks commonly used to assess bipolar patients do not seem accurate to identify suicide attempters in euthymic patients. In the future, decision-making and emotional recognition tasks should be assessed. Moreover, clinical and neuropsychological profiles should be considered together to better define suicidal risk. PMID- 25131521 TI - Fibroadenomatosis involving bilateral breasts and axillary accessory breast tissues in a renal transplant recipient given cyclosporin A. AB - We present the mammographic and sonographic findings in a case of fibroadenomatosis involving both breasts and axillae in a renal transplant patient after 16 years of treatment with cyclosporin A. Awareness of the fact that cyclosporin A may induce the formation of fibroadenomas, including in accessory breast tissue, is important for correct diagnosis and preventing unnecessary intervention. PMID- 25131520 TI - Correlation between congenital heart defects and maternal copper and zinc concentrations. AB - BACKGROUND: The aim of this study was to investigate the correlation between maternal concentrations of copper and zinc and the risk of having an infant with a congenital heart defect (CHD). METHODS: A multi-center hospital-based case control study was conducted in China. A total of 212 cases and 212 controls were recruited from pregnant women who received prenatal examinations in four tertiary hospitals accredited to perform prenatal diagnosis in the cities of Shenzhen, Zhenzhou, Fuzhou and Wuhan between February 2010 and November 2011. Correlation between CHDs and maternal copper and zinc concentrations was estimated by a 1:1 conditional logistic regression. Also the interaction between copper and zinc was analyzed. RESULTS: Compared with the controls, mothers with hair copper concentrations of 17.77 MUg/g or more were more likely to have a child with a CHD than those with a lower concentration. The adjusted odds ratio was 5.70 (95% confidence interval, 2.58-12.61) for CHDs and 6.32 (95% confidence interval, 2.11 18.92) for conotruncal defects. Zinc concentrations were not significantly different in the case and control groups. The results suggest that mothers whose zinc content was 104.60 MUg/g or less did not have a significantly higher risk of having a child with a CHD. No interaction between maternal copper and zinc concentrations was observed in the multiplicative or additive model. CONCLUSION: Women with excessive copper concentrations have a significantly increased risk of having offspring with a CHD. A low maternal zinc status might have a correlation with CHDs, and an interaction between copper and zinc might exists, but an epidemiological study with a larger sample size is needed to confirm this finding. PMID- 25131523 TI - Usefulness of lewis lead for visualizing p-wave. PMID- 25131522 TI - Novel tricyclic[2,1-f]theophylline derivatives of LCAP with activity in mouse models of affective disorders. AB - OBJECTIVES: The purpose of this study was to investigate the central activity of the two new imidazo[2,1-f]purine-2,4-dione derivatives behaved as presynaptic 5HT1A receptor agonists and postsynaptic 5HT1A , 5HT2A and D2 receptors antagonists. The compounds were examined using animal tests towards antipsychotic, antidepressant- and anxiolytic-like properties and then compared with effects evoked by an atypical antipsychotic drug ziprasidone. METHODS: D amphetamine-induced hyperactivity test was used to determine antipsychotic-like activity of compounds 7 and 9. The forced swim test (FST) and the four-plate test were conducted to investigate antidepressant- and antianxiety-like activity, respectively, of studied agents. The investigated compounds 7, 9 and ziprasidone were administered intraperitoneally 60 min before the tests. Diazepam and imipramine were used as standard anxiolytic and antidepressant drugs, respectively. KEY FINDINGS: The obtained results demonstrate that new synthesized compound 9 evokes antipsychotic-like activity alike ziprasidone and, in contrary to the antipsychotic drug, shows antidepressant- and anxiolytic-like properties in behavioural tests in mice. CONCLUSIONS: The present preclinical results indicate that one of the two investigated imidazo[2,1-f]purine-2,4-dione derivatives, compound 9, with methyl group at 7 position of imidazo[2,1-f]purine 2,4-dione fragment and the ortho-OCH3 substituent in the aryl moiety, acts as an antipsychotic drug with additional antidepressant and anxiolytic properties. PMID- 25131524 TI - Spontaneous coronary artery dissection. AB - Spontaneous coronary artery dissection (SCAD) is a rare but challenging clinical entity of unknown etiology. From a pathophysiological standpoint, SCAD may occur in patients with a coronary intimal tear (presenting with the classic angiographic "flap" and multiple lumens), but also in patients without an intimal rupture (presenting as an intramural hematoma). Until now, available information on SCAD was largely based on multiple, small case-series studies but, recently, data from relatively large registries have cast a new light on this disease. Classically, SCAD was thought to present in young females without traditional atherosclerotic risk factors but recent reports suggest a broader clinical spectrum encompassing older patients with associated coronary artery disease. In this review, we concentrate on 3 main aspects of this unique disease: (1) the value of intracoronary diagnostic techniques (intravascular ultrasound and optical coherence tomography) to complement coronary angiography and to provide novel diagnostic insights on this elusive clinical condition; (2) the growing clinical evidence suggesting an association and potential causation between fibromuscular dysplasia and SCAD; and (3) the challenges of coronary revascularization in this adverse anatomic setting, together with recent data suggesting that a initial, conservative medical management may be preferable for the majority of patients with SCAD. PMID- 25131525 TI - Diagnosis of Takotsubo cardiomyopathy. AB - Takotsubo cardiomyopathy, also known as left ventricular apical ballooning syndrome and stress-induced cardiomyopathy, is typically characterized by transient systolic dysfunction of the apical and mid-segments of the left ventricle, in the absence of obstructive coronary artery lesions. Patients may present with symptoms and signs of acute coronary syndrome, and the provider is challenged to differentiate between these conditions. In this review, we guide the reader through the diagnostic pathway, focusing on differential diagnoses and diagnostic criteria for takotsubo cardiomyopathy. PMID- 25131526 TI - [Post-stroke depression]. AB - Cerebrovascular diseases are associated with a high incidence of psychiatric disorders. Depressive illness after stroke has been extensively investigated during the last three decades. Post-stroke depression is estimated to occur in 30 35% of the patients during the first year after stroke. Numerous studies have given information on its prevalence, pathogenesis, clinical course, treatment and prevention. Despite the high level of comorbidity, depressive symptoms appear to remain frequently unrecognized and untreated. This has a negative effect on the rehabilitation, quality of live, cognitive function and mortality of stroke patients. PMID- 25131527 TI - [Cardiovascular screening programme in the Central Hungarian region. The Budakalasz Study]. AB - INTRODUCTION: The reduction in mortality due to prevention programmes observed in some European countries is not currently reached in Hungary. Effective prevention is based on the screening of risk factors and health state of the population. AIM: The goal of this study was to develop a longitudinal, population-based screening programme in the Central Hungarian region in order to collect information on the health state and cardiovascular risk profile of the citizens and discover new potential cardiovascular risk factors. METHOD: The Budakalasz Study is a self-voluntary programme involving the adult population (>20 yrs, approx. 8000 persons), and it consists of questionnaires, non-invasive tests (anthropometry, cardiac echo, carotid duplex scan, blood pressure measurement, ankle-brachial index), venous blood sample collection and laboratory tests. RESULTS: Until January, 2014, 2420 persons (30% of the population, male: 41.2%, average age 54.8 years) participated in the programme. Cardiovascular morbidity was higher in contrast to a former national survey. The number of risk factors and, therefore, 10-year cardiovascular risk were also elevated in this population. CONCLUSIONS: These findings underline the importance of screening programmes and effective therapies. PMID- 25131528 TI - [International comparative study on health condition of young people]. AB - INTRODUCTION: The connection between physical condition, coping strategies and emotional intelligence is widely studied in the international literature, but comparative research data collected among Transylvanian and Hungarian adolescents are not available in contemporary psychological literature. AIM: The aim of the authors was to study health indicators, emotional intelligence and coping strategies among adolescents and analyse connections between these factors and physical condition as part of an international research. METHOD: The physical condition, coping strategies and emotional intelligence of 390 individuals, aged between 13 and 19 years living in Debrecen (Hungary) and Ermihalyfalva (Romania) were observed. RESULTS: adaptive (i. e. problem-focused) coping strategies used in stressful situations resulted in lower depression rates, as well as better mental well-being than the maladaptive ones such as emotional clearing, self punishment, distraction of attention. Adolescents showing higher emotional intelligence had lower depression levels and better mental well-being. CONCLUSIONS: Institutionally initiated emotional intelligence and coping strategy development for young people may prove to be an important preventive interventional public health programme. This may serve as a basis to assist health-consciousness and personality formatting. PMID- 25131529 TI - [Patient rights in the remote past? Regulation of medical services until the 19th century, based particularly on Hungary's first comprehensive Royal Decree of the health system]. PMID- 25131530 TI - [The place of our Earth in the cosmos and the turning points in its history- thoughts related to climate change]. PMID- 25131533 TI - Acute fatal upper airway obstruction from an occult cavernous hemangioma of the larynx. AB - A 42-year-old previously well man collapsed while holding his throat. Resuscitation was unsuccessful, and at autopsy, the most significant findings were limited to the larynx, pharynx, and anterior mediastinum where there were multinodular dark blue tumors. Within the larynx, the lower border of the tumor was well demarcated, not extending beyond the vocal cords. A separate large polypoidal tumor mass was attached to the right aryepiglottic fold by a thin fibrous stalk. Histologic examination revealed numerous large, thin-walled cavernous-type vascular spaces typical of a multifocal cavernous hemangioma. Death was due to asphyxiation from obstruction of the upper airways by a cavernous hemangioma of the larynx. Adult laryngeal hemangiomas are rare and are usually supraglottic. This case demonstrates that pedunculated laryngeal cavernous hemangiomas may remain occult until the initiation of an obstructive episode with sudden collapse and death. In such instances, the diagnosis must rely upon an autopsy examination. PMID- 25131531 TI - alphabetaT cell receptors expressed by CD4(-)CD8alphabeta(-) intraepithelial T cells drive their fate into a unique lineage with unusual MHC reactivities. AB - Coreceptor CD4 and CD8alphabeta double-negative (DN) TCRalphabeta(+) intraepithelial T cells, although numerous, have been greatly overlooked and their contribution to the immune response is not known. Here we used T cell receptor (TCR) sequencing of single cells combined with retrogenic expression of TCRs to study the fate and the major histocompatibility complex (MHC) restriction of DN TCRalphabeta(+) intraepithelial T cells. The data show that commitment of thymic precursors to the DN TCRalphabeta(+) lineage is imprinted by their TCR specificity. Moreover, the TCRs they express display a diverse and unusual pattern of MHC restriction that is nonoverlapping with that of CD4(+) or CD8alphabeta(+) T cells, indicating that they sense antigens that are not recognized by the conventional T cell subsets. The new insights indicate that DN TCRalphabeta(+) T cells form a third lineage of TCRalphabeta T lymphocytes expressing a variable TCR repertoire, which serve nonredundant immune functions. PMID- 25131532 TI - Elevated T cell receptor signaling identifies a thymic precursor to the TCRalphabeta(+)CD4(-)CD8beta(-) intraepithelial lymphocyte lineage. AB - The origin and developmental pathway of intestinal T cell receptor alphabeta(+) CD4(-)CD8beta(-) intraepithelial lymphocytes (unconventional iIELs), a major population of innate-like resident cytolytic T cells, have remained elusive. By cloning and expressing several TCRs isolated from unconventional iIELs, we identified immature CD4(lo)CD8(lo)(DP(lo))CD69(hi)PD-1(hi) thymocytes as the earliest postsignaling precursors for these cells. Although these precursors displayed multiple signs of elevated TCR signaling, a sizeable fraction of them escaped deletion to selectively engage in unconventional iIEL differentiation. Conversely, TCRs cloned from DP(lo)CD69(hi)PD-1(hi) thymocytes, a population enriched in autoreactive thymocytes, selectively gave rise to unconventional iIELs upon transgenic expression. Thus, the unconventional iIEL precursor overlaps with the DP(lo) population undergoing negative selection, indicating that, concomitant with the downregulation of both CD4 and CD8 coreceptors, a balance between apoptosis and survival signals results in outcomes as divergent as clonal deletion and differentiation to the unconventional iIEL lineage. PMID- 25131534 TI - Risk of drug-induced liver injury from tumor necrosis factor antagonists. AB - BACKGROUND & AIMS: Antagonists of tumor necrosis factor (anti-TNF agents) can cause drug-induced liver injury (DILI), yet little is known about the level of risk. METHODS: We identified cases of DILI caused by anti-TNF agents in Iceland, from 2009 through 2013, at the National University Hospital of Iceland (n = 11). We collected data on the total use of the drugs by patients with DILI, and outcomes, compared with patients who received anti-TNF agents but who did not develop DILI (controls, n = 22). RESULTS: Of the 11 cases of DILI identified (8 women; mean age, 46 y), 9 cases were caused by infliximab. DILI developed in 1 of 120 patients who received infliximab, 1 in 270 patients who received adalimumab, and 1 in 430 patients who received etanercept. Most patients with infliximab associated DILI developed this disorder after 4 infusions (n = 6). Four patients had jaundice at diagnosis of DILI, and 8 patients had hepatocellular liver injury. The mean peak level of alanine aminotransferase was 704 U/L, of aspartate aminotransferase was 503 U/L, of alkaline phosphatase was 261 U/L, and of bilirubin was 47 MUmol/L. Seven patients with DILI were tested for antinuclear antibodies before therapy with an anti-TNF agent and 3 had positive test results, compared with 5 of the 14 controls tested. At DILI diagnosis, 8 of 11 patients tested positive for antinuclear antibodies. Of liver biopsy specimens collected from 5 patients with DILI, 3 showed signs of severe acute hepatitis. Only 9% of the patients who developed DILI received methotrexate during anti-TNF therapy, compared with 59% of controls (P = .009). DILI was treated with steroids in 5 patients, and in 4 cases steroid therapy was discontinued without relapse. Eight patients with DILI went on to receive treatment with different TNF antagonists without developing DILI. CONCLUSIONS: Of anti-TNF agents, infliximab is associated most frequently with DILI, developing in 1 of 120 patients who received this drug. Fifty percent of patients with anti-TNF-associated DILI required steroid therapy, but most did not need long-term treatment. The addition of methotrexate to anti-TNF therapy might reduce the risk of DILI. PMID- 25131535 TI - Structural and mutational studies on an aldo-keto reductase AKR5C3 from Gluconobacter oxydans. AB - An aldo-keto reductase AKR5C3 from Gluconobacter oxydans (designated as Gox0644) is a useful enzyme with various substrates, including aldehydes, diacetyl, keto esters, and alpha-ketocarbonyl compounds. The crystal structures of AKR5C3 in apoform in complex with NADPH and the D53A mutant (AKR5C3(-D53A) ) in complex with NADPH are presented herein. Structure comparison and site-directed mutagenesis combined with biochemical kinetics analysis reveal that the conserved Asp53 in the AKR5C3 catalytic tetrad has a crucial role in securing active pocket conformation. The gain-of-function Asp53 to Ala mutation triggers conformational changes on the Trp30 and Trp191 side chains, improving NADPH affinity to AKR5C3, which helps increase catalytic efficiency. The highly conserved Trp30 and Trp191 residues interact with the nicotinamide moiety of NADPH and help form the NADPH binding pocket. The AKR5C3(-W30A) and AKR5C3(-W191Y) mutants show decreased activities, confirming that both residues facilitate catalysis. Residue Trp191 is in the loop structure, and the AKR5C3(-W191Y) mutant does not react with benzaldehyde, which might also determine substrate recognition. Arg192, which is involved in the substrate binding, is another important residue. The introduction of R192G increases substrate-binding affinity by improving hydrophobicity in the substrate-binding pocket. These results not only supplement the AKRs superfamily with crystal structures but also provide useful information for understanding the catalytic properties of AKR5C3 and guiding further engineering of this enzyme. PMID- 25131536 TI - Design, synthesis, in silico and in vitro studies of novel 4-methylthiazole-5 carboxylic acid derivatives as potent anti-cancer agents. AB - Since inhibitors of mucin onco proteins are potential targets for breast cancer therapy, a series of novel 4-methylthiazole-5-carboxylic acid (1) derivatives 3a k were synthesized by the reaction of 1 with SOCl2 followed by different bases/alcohols in the presence of triethylamine. Once synthesized and characterized, their binding modes with MUC1 were studied by molecular docking analysis using Aruglab 4.0.1 and QSAR properties were determined using HyperChem. All synthesized compounds were screened for in vitro anti-breast cancer activity against MDA-MB-231 breast adenocarcinoma cell lines by Trypan-blue cell viability assay and MTT methods. Compounds 1, 3b, 3d, 3e, 3i and 3f showed good anti-breast cancer activity. Since 1 and 3d exhibited high potent activity against MDA-MB-231 cell lines, they show could be effective mucin onco protein inhibitors. PMID- 25131537 TI - Inhibition of activated STAT5 in Bcr/Abl expressing leukemia cells with new pimozide derivatives. AB - STATs are transcription factors acting as intracellular signaling after stimulation with cytokines, growth factors and hormones. STAT5 is also constitutively active in many forms of cancers, including chronic myelogenous leukemia, acute lymphoblastic leukemia and Hodgkin's lymphoma. Recently, literature reported that the neuroleptic drug pimozide inhibits STAT5 phosphorylation inducing apoptosis in CML cells. We undertook an investigation from pimozide structure, obtaining simple derivatives with cytotoxic and STAT5 inhibitory activity, two of them markedly more potent than pimozide. PMID- 25131538 TI - Screening and identification of novel compounds with potential anti-proliferative effects on gallium-resistant lung cancer through an AXL kinase pathway. AB - The clinical application of gallium compounds as anticancer agents is hampered by development of resistance. As a potential strategy to overcome the limitation, eight series of compounds were identified through virtual screening of AXL kinase homology model. Anti-proliferative studies were carried using gallium-sensitive (S) and gallium-resistant (R) human lung adenocarcinoma (A549) cells. Compounds 5476423 and 7919469 were identified as leads. The IC50 values from treating R cells showed compounds 5476423 and 7919469 had 80 fold and 13 fold increased potency, respectively, compared to gallium acetylacetonate (GaAcAc). The efficacy of GaAcAc against R-cells was increased 2 fold and 1.2 fold when combined with compounds 5476423 and 7919469, respectively. Compared with S-cells, R-cells showed elevated expression of AXL protein, which was significantly suppressed through treatments with the lead compounds. It is anticipated that the lead compounds could be applied in virtual screening programs to identify novel scaffolds for new therapeutic agents as well as combinatorial therapy agents in gallium resistant lung cancer. PMID- 25131539 TI - Synthesis, in vitro and in silico studies of a PPARgamma and GLUT-4 modulator with hypoglycemic effect. AB - Compound {4-[({4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5 ylidene)methyl]phenoxy}acetyl)amino]phenoxy}acetic acid (1) was prepared and the in vitro relative expression of PPARgamma, GLUT-4 and PPARalpha, was estimated. Compound 1 showed an increase of 2-fold in the mRNA expression of PPARgamma isoform, as well as the GLUT-4 levels. The antidiabetic activity of compound 1 was determined at 50 mg/Kg single dose using a non insulin dependent diabetes mellitus (NIDDM) rat model. The in vivo results indicated a significant decrease of plasma glucose levels, during the 7 h post-administration. Also, we performed a molecular docking of compound 1 into the ligand binding pocket of PPARgamma, showing important short contacts with residues Ser289, His323 and His449 in the active site. PMID- 25131540 TI - Correlates of quality of sexual life in male and female patients with Parkinson disease and their partners. AB - INTRODUCTION: Patients with Parkinson disease (PD) and their partners may experience a worsening of their sexual life. AIM: To assess quality of sexual life (QoSL) in male and female PD patients and their partners. MATERIALS AND METHODS: Medical, demographic and clinical data was collected regarding consecutive PD patients, including depression, and motor symptom rating. Partners' data included the short form-12 health questionnaire (SF-12). All patients and partners filled the 5-item QoSL questionnaire. RESULTS: Data from 89 PD patients (66 men) and 69 spouses (52 women) was analyzed. Male patients rejected sex significantly less than female patients and their sexual desire was higher, but female patients reported higher sexual satisfaction. Patients and partners similarly perceived their relationship which was averagely good. Analysis within couples demonstrated that better QoSL of patients could be predicted by gender (male), better QoSL of their partners and, motor severity, but not the patient's depression, age or use of l-dopa. The partner's QoSL was explained by younger age, and better motor scores of their parkinsonian partner. Treatment of the PD patient with l-dopa or dopamine agonist was associated with worse partner's QoSL. CONCLUSION: Differences in QoSL of male and female PD patients and within couples were found. These findings suggest that focusing on partner's needs may improve QoSL of patients and partners troubled by PD. PMID- 25131542 TI - Transgenerational epigenetics and brain disorders. AB - Neurobehavioral and psychiatric disorders are complex diseases with a strong heritable component; however, to date, genome-wide association studies failed to identify the genetic loci involved in the etiology of these brain disorders. Recently, transgenerational epigenetic inheritance has emerged as an important factor playing a pivotal role in the inheritance of brain disorders. This field of research provides evidence that environmentally induced epigenetic changes in the germline during embryonic development can be transmitted for multiple generations and may contribute to the etiology of brain disease heritability. In this review, we discuss some of the most recent findings on transgenerational epigenetic inheritance. We particularly discuss the findings on the epigenetic mechanisms involved in the heritability of alcohol-induced neurobehavioral disorders such as fetal alcohol spectrum disorders. PMID- 25131544 TI - Epigenetic regulatory mechanisms in stress-induced behavior. AB - Stress response is considered to have adaptive value for organisms faced with stressful condition. Chronic stress however adversely affects the physiology and may lead to neuropsychiatric disorders. Repeated stressful events in animal models have been shown to cause long-lasting changes in neural circuitries at molecular, cellular, and physiological level, leading to disorders of mood as well as cognition. Molecular studies in recent years have implicated diverse epigenetic mechanisms, including histone modifications, DNA methylation, and noncoding RNAs, that underlie dysregulation of genes in the affected neural circuitries in chronic stress-induced pathophysiology. A review of the myriad epigenetic regulatory mechanisms associated with neural and behavioral responses in animal models of stress-induced neuropsychiatric disorders is presented here. The review also deals with clinical evidence of the epigenetic dysregulation of genes in psychiatric disorders where chronic stress appears to underlie the etiopathology. PMID- 25131545 TI - Epigenetics of schizophrenia: an open and shut case. AB - During the last decade and a half, there has been an explosion of data regarding epigenetic changes in schizophrenia. Most initial studies have suggested that schizophrenia is characterized by an overly restrictive chromatin state based on increases in transcription silencing histone modifications and DNA methylation at schizophrenia candidate gene promoters and increases in the expression of enzymes that catalyze their formation. However, recent studies indicate that the pathology is more complex. This complexity may greatly impact pharmacological approaches directed at targeting epigenetic abnormalities in schizophrenia. The current review explores epigenetic studies of schizophrenia and what this can tell us about the underlying pathophysiology. We hypothesize based on recent studies that it is also plausible that drugs that further restrict chromatin may be efficacious. PMID- 25131546 TI - Epigenetic mechanisms in autism spectrum disorder. AB - Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social interactions, language deficits, as well as restrictive or repetitive behaviors. ASD is clinically heterogeneous with a complex etiopathogenesis which may be conceptualized as a dynamic interplay between heterogeneous environmental cues and predisposing genetic factors involving complex epigenetic mechanisms. Inherited and de novo copy number variants provide novel information regarding genes contributing to ASD. Epigenetic marks are stable, yet potentially reversible, chromatin modifications that alter gene expression profiles by locally changing the degree of nucleosomal compaction, thereby opening or closing promoter access to the transcriptional machinery. Here, we review progress on studies designed to provide a better understanding of how epigenetic mechanisms impact transcriptional programs operative in the brain that contribute to ASD. PMID- 25131547 TI - MicroRNAs and ethanol toxicity. AB - MicroRNAs (miRNAs) are a class of small nonprotein-coding RNAs (ncRNAs) that have been shown to promote the degradation of target messenger RNAs and inhibit the translation of networks of protein-coding genes to control the development of cells and tissues, and facilitate their adaptation to environmental forces. In this chapter, we will discuss recent data that show that miRNAs are an important component of the epigenetic landscape that regulates the transcription as well as the translation of protein-coding gene networks. We will discuss the evidence that implicates miRNAs in both developmental and adult effects of alcohol consumption. Understanding the interactions of this novel class of ncRNAs with the epigenome will be important for understanding the etiology of alcohol teratology and addiction as well as potential new treatment strategies. PMID- 25131548 TI - Preface. Epigenetics. PMID- 25131549 TI - A new way forward: improving maternal and child health in America. PMID- 25131541 TI - Environmental alterations of epigenetics prior to the birth. AB - The etiology of many brain diseases remains allusive to date after intensive investigation of genomic background and symptomatology from the day of birth. Emerging evidences indicate that a third factor, epigenetics prior to the birth, can exert profound influence on the development and functioning of the brain and over many neurodevelopmental syndromes. This chapter reviews how aversive environmental exposure to parents might predispose or increase vulnerability of offspring to neurodevelopmental deficit through alteration of epigenetics. These epigenetic altering environmental factors will be discussed in the category of addictive agents, nutrition or diet, prescriptive medicine, environmental pollutant, and stress. Epigenetic alterations induced by these aversive environmental factors cover all aspects of epigenetics including DNA methylation, histone modification, noncoding RNA, and chromatin modification. Next, the mechanisms how these environmental inputs influence epigenetics will be discussed. Finally, how environmentally altered epigenetic marks affect neurodevelopment is exemplified by the alcohol-induced fetal alcohol syndrome. It is hoped that a thorough understanding of the nature of prenatal epigenetic inputs will enable researchers with a clear vision to better unravel neurodevelopmental deficit, late-onset neuropsychiatric diseases, or idiosyncratic mental disorders. PMID- 25131550 TI - Magnet application in ICD patients. PMID- 25131551 TI - Smart vesicle kit for in situ monitoring of intracellular telomerase activity using a telomerase-responsive probe. AB - A smart vesicle kit was designed for in situ imaging and detection of cytoplasmic telomerase activity. The vesicle kit contained a telomerase primer (TSP) and a Cy5-tagged molecular beacon (MB) functionalized gold nanoparticle probe, which were encapsulated in liposome for intracellular delivery. After the vesicle kit was transfected into cytoplasm, the released TSP could be extended in the presence of telomerase to produce a telomeric repeated sequence at the 3' end, which was just complementary with the loop of MB assembled on probe surface. Thus, the MB was opened upon hybridization to switch the fluorescent state from "off" to "on". The fluorescence signal depended on telomerase activity, leading to a novel strategy for in situ imaging and quantitative detection of the cytoplasmic telomerase activity. The cytoplasmic telomerase activity was estimated to be 3.2 * 10(-11), 2.4 * 10(-11), and 8.6 * 10(-13) IU in each HeLa, BEL tumor and QSG normal cell, respectively, demonstrating the capability of this approach to distinguish tumor from normal cells. The proposed method could be employed for dynamic monitoring of the cytoplasmic telomerase activity in response to a telomerase-based drug, suggesting the potential application in discovery and screening of telomerase-targeted anticancer drugs. PMID- 25131552 TI - The object of sexual desire: examining the "what" in "what do you desire?". AB - INTRODUCTION: Over the past two decades, sexual desire and desire discrepancy have become more frequently studied as have potential pharmaceutical interventions to treat low sexual desire. However, the complexities of sexual desire-including what exactly is desired-remain poorly understood. AIMS: To understand the object of men's and women's sexual desire, evaluate gender differences and similarities in the object of desire, and examine the impact of object of desire discrepancies on overall desire for partner in men and women in the context of long-term relationships. METHODS: A total of 406 individuals, 203 men and 203 women in a relationship with one another, completed an online survey on sexual desire. MAIN OUTCOME MEASURES: Reports of the object of sexual desire in addition to measures of sexual desire for current partner were collected from both members of the couple. RESULTS: There were significant gender differences in the object of sexual desire. Men were significantly more likely to endorse desire for sexual release, orgasm, and pleasing their partner than were women. Women were significantly more likely to endorse desire for intimacy, emotional closeness, love, and feeling sexually desirable than men. Discrepancies within the couple with regard to object of desire were related to their level of sexual desire for partner, accounting for 17% of variance in men's desire and 37% of variance in women's desire. CONCLUSIONS: This research provides insights into the conceptualization of sexual desire in long-term relationships and the multifaceted nature of sexual desire that may aid in more focused ways to maintain desire over long-term relationships. Future research on the utility of this perspective of sexual desire and implications for clinicians working with couples struggling with low sexual desire in their relationships is discussed. PMID- 25131543 TI - The epigenetic landscape of alcoholism. AB - Alcoholism is a complex psychiatric disorder that has a multifactorial etiology. Epigenetic mechanisms are uniquely capable of accounting for the multifactorial nature of the disease in that they are highly stable and are affected by environmental factors, including alcohol itself. Chromatin remodeling causes changes in gene expression in specific brain regions contributing to the endophenotypes of alcoholism such as tolerance and dependence. The epigenetic mechanisms that regulate changes in gene expression observed in addictive behaviors respond not only to alcohol exposure but also to comorbid psychopathology such as the presence of anxiety and stress. This review summarizes recent developments in epigenetic research that may play a role in alcoholism. We propose that pharmacologically manipulating epigenetic targets, as demonstrated in various preclinical models, hold great therapeutic potential in the treatment and prevention of alcoholism. PMID- 25131553 TI - A pathogenicity determinant maps to the N-terminal coat protein region of the Pepino mosaic virus genome. AB - Pepino mosaic virus (PepMV) poses a worldwide threat to the tomato industry. Considerable differences at the genetic level allow for the distinction of four main genotypic clusters; however, the basis of the phenotypic outcome is difficult to elucidate. This work reports the generation of wild-type PepMV infectious clones of both EU (mild) and CH2 (aggressive) genotypes, from which chimeric infectious clones were created. Phenotypic analysis in three solanaceous hosts, Nicotiana benthamiana, Datura stramonium and Solanum lycopersicum, indicated that a PepMV pathogenicity determinant mapped to the 3'-terminal region of the genome. Increased aggression was only observed in N. benthamiana, showing that this factor is host specific. The determinant was localized to amino acids 11-26 of the N-terminal coat protein (CP) region; this is the first report of this region functioning as a virulence factor in PepMV. PMID- 25131554 TI - Pregnancy outcome according to male diagnosis after ICSI with non-ejaculated sperm compared with ejaculated sperm controls. AB - The aim of this study was to describe pregnancy outcome in couples who had undergone ICSI using non-ejaculated sperm from men with non-obstructive azoospermia, obstructive azoospermia and aspermia compared with the outcome of ICSI with ejaculated sperm from men with severe oligozoospermia, treated during the same time period. This nationwide cohort study included all children born after ICSI with non-ejaculated sperm in Norway, from when the method was first permitted in Norway in April 2004 to the end of 2010, resulting in 420 pregnancies and a total of 359 children. In 235 of these children, the father was diagnosed with obstructive azoospermia, in 72 with non-obstructive azoospermia, in 31 with aspermia, and in 21 the male cause was unclassifiable. The control group consisted of 760 children from 939 pregnancies conceived by ICSI with ejaculated sperm. Sex ratio, birth weight, rate of pregnancy loss and congenital malformations were not significantly associated with sperm origin or the cause of male factor infertility. PMID- 25131555 TI - The long-term experiences of surrogates: relationships and contact with surrogacy families in genetic and gestational surrogacy arrangements. AB - This study examined the contact arrangements and relationships between surrogates and surrogacy families and whether these outcomes differed according to the type of surrogacy undertaken. Surrogates' motivations for carrying out multiple surrogacy arrangements were also examined, and surrogates' psychological health was assessed. Semi-structured interviews were administered to 34 women who had given birth to a child conceived through surrogacy approximately 7 years prior to interview. Some surrogates had carried out multiple surrogacy arrangements, and data were collected on the frequency, type of contact, and surrogate's feelings about the level of contact in each surrogacy arrangement, the surrogate's relationship with each child and parent, and her experience of, and motivation for, each surrogacy. Questionnaire measures of psychological health were administered. Surrogates had completed a total of 102 surrogacy arrangements and remained in contact with the majority of families, and reported positive relationships in most cases. Surrogates were happy with their level of contact in the majority of arrangements and most were viewed as positive experiences. Few differences were found according to surrogacy type. The primary motivation given for multiple surrogacy arrangements was to help couples have a sibling for an existing child. Most surrogates showed no psychological health problems at the time of data collection. PMID- 25131556 TI - Androgen receptor CAG repeat length is associated with ovarian reserve but not with ovarian response. AB - The human androgen receptor (AR) gene contains a highly polymorphic CAG repeat sequence within exon 1. In-vitro studies have shown a relationship between CAG repeats in the AR gene and its transactivation potential. This variation in length may play a role in anovulatory infertility. The objective of this study was to investigate whether CAG polymorphism of the AR gene has a predictive value for ovarian reserve, response and cycle outcome in an egg donor programme. CAG length of the AR gene was determined in 147 oocyte donors. All donors underwent ovarian stimulation with a gonadotrophin-releasing hormone antagonist protocol (n = 355). No differences were reported in days of stimulation, gonadotrophin doses, and number of oocytes retrieved. Clinical outcomes were not affected by the CAG repeat length of the AR gene; the primary end-point, antral follicle count, was significantly affected (P < 0.05). In conclusion, in a population of fertile egg donors AR gene CAG polymorphism does not affect ovarian response to gonadotrophins. Antral follicle count was associated with the CAG polymorphism genotype. This suggests that genetic factors may increase susceptibility to poor ovarian reserve, and that AR gene genotype could play a role in the natural ovarian ageing process. PMID- 25131557 TI - Effect of chromosomal polymorphisms of different genders on fertilization rate of fresh IVF-ICSI embryo transfer cycles. AB - To explore whether chromosomal polymorphisms of different genders affect outcomes of fresh IVF and intracytoplasmic sperm injection (ICSI) embryo transfer cycles differently, 37 couples with chromosomal polymorphisms were identified out of 614 infertile couples undergoing IVF-ICSI treatments. Group 1 included 20 couples in which only the male carried chromosomal polymorphisms; group 2 included 17 couples with female carriers only; group 3 included 19 infertile couples with normal karyotypes randomly selected as controls. A significantly lower fertilization rate was found in group 1 compared with groups 2 and 3 (56.68% in Group 1, 78.02% in group 2 and 71.74% in group 3; group 1 versus group 2, P < 0.001; group 1 versus group 3, P = 0.001; respectively). When stratified according to fertilization method, the fertilization rate in IVF cycles of group 1 was significantly lower than group 3 (50.00% in Group 1, 73.89% in Group 3, P < 0.001). Fertilization rates in ICSI cycles between groups 1 and 3 were not significantly different. This study suggests that male chromosomal polymorphisms adversely influence fertilization rates of IVF cycles. The use of ICSI may improve the success of infertility treatment by increasing the fertilization rate for men with chromosomal polymorphisms. PMID- 25131558 TI - In-vitro culture system for mesenchymal progenitor cells derived from waste human ovarian follicular fluid. AB - To characterize different cell populations in the human ovary, morphological and functional characteristics of cell populations collected during routine IVF procedures were studied. Cells obtained from follicular fluid grew in vitro under minimal medium conditions, without growth factor, including leukaemia-inhibiting factor. Morphological analysis revealed a heterogeneous cell population, with cells displaying a fibroblast-like, epithelial-like and also neuron-like features. Morpho-functional characteristics of fibroblast-like cells were similar to mesenchymal stem cells, and, in particular, were positive for mesenchymal stemness markers, including CD90, CD44, CD105, CD73, but negative for epithelial proteins, such as cytokeratins, CD34 and CD45 antigens. Cell proliferation activity at different times and colony-forming unit capability were evaluated, and multipotency of a subset of granulosa cells was established by in-vitro differentiation studies (e.g. osteogenic, chondrogenic and adipogenic differentiation). This study suggests that cells provided by mesenchymal plasticity can be easily isolated by waste follicular fluid, avoiding scraping of human ovaries, and cultivated in minimal conditions. Successful growth of such progenitor cells on three-dimensional cryogel scaffold provides the basis for future developments in tissue engineering. This culture system may be regarded as an experimental model in which biological behaviour is not influenced by specific growth factors. PMID- 25131559 TI - Quadrivalent asymmetry in reciprocal translocation carriers predicts meiotic segregation patterns in cleavage stage embryos. AB - The effect of quadrivalent geometry on meiotic behaviour was evaluated. Segregation patterns of 404 cleavage stage embryos from 40 reciprocal translocation carriers undergoing 75 PGD cycles were analysed according to the asymmetric degree of quadrivalent. The percentage of alternate products with severe asymmetric quadrivalents was significantly lower than patients with mild asymmetric quadrivalents (22.5% versus 38.7%, P = 0.001). The incidence of 3:1 products was significantly higher in patients with severe compared with mild asymmetric quadrivalents (23.1% versus 12.2%, P = 0.004). The incidence of adjacent 1 (25.8% versus 24.3%), 2 (11.5% versus 12.6%) and 4:0/other segregation products (17.0% versus 12.2%) were not statistically significantly different between embryos from patients with severe or mild asymmetric quadrivalents. After adjusting for the confounder of sex using a logistic regression model, the odds of alternate embryos is about one-half for carriers classified as severe (OR 0.456, 95% CI 0.291 to 0.705), and the odds of 3:1 embryos is 2.2 times higher for carriers with severe asymmetric quadrivalents (OR 2.235, 95% CI 1.318 to 3.846). Our results suggest that the meiotic segregation pattern is related to the degree of asymmetry of specific quadrivalents. Severe asymmetric quadrivalents increases the risk of abnormal embryos. PMID- 25131560 TI - Association of serum uric acid levels to inflammation biomarkers and endothelial dysfunction in obese prepubertal children. AB - BACKGROUND: High serum uric acid (SUA) levels are present in patients with metabolic syndrome (MetS), when the latter is associated with endothelial dysfunction, inflammation, and hypertension. This increase in SUA levels may have a key role in cardiovascular diseases. OBJECTIVE: We aim to quantify the differences in inflammation biomarkers, endothelial dysfunction, and parameters associated with MetS in obese prepubertal children compared to non-obese children, and determine if there is a relationship between uric acid levels and these variables. METHODS: A cross-sectional study was carried out on obese children (6-9 yr old). The study included 43 obese children and the same number of non-obese children (control group), matched by age and sex. SUA, C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), glucose, insulin, lipid profile, and blood pressure were all measured. RESULTS: SUA levels, CRP, and sICAM-1 were significantly higher in obese children. In the obese group, SUA levels showed a positive correlation with body mass index (BMI), insulin, homeostasis model assessment for insulin resistance (HOMA-IR), CRP, IL-6, sICAM-1, and triglycerides (TGs), and correlated negatively with high-density lipoprotein cholesterol (HDL-C) and Apo-AI, but not with Apo-B. When adjusted for age, sex, and creatinine, it was noted that SUA levels are independent predictive factors for sICAM-1, CRP, and IL-6. CONCLUSIONS: Inflammation biomarkers, endothelial dysfunction, and parameters associated with MetS are elevated in obese prepubertal children and correlate to uric acid levels. PMID- 25131561 TI - Ex vivo-expanded natural killer cells kill cancer cells more effectively than ex vivo-expanded gammadelta T cells or alphabeta T cells. AB - Adoptive immunotherapy of cancer is evolving with the development of novel technologies for generating a large number of activated killer cells such as natural killer (NK) cells, gammadelta T cells, and alphabeta T cells. We have recently established large-scale culture methods to generate activated NK cells from human peripheral blood, and demonstrated that expanded NK cells have higher cytotoxicity against cancer cells than freshly isolated NK cells. In this study, we compared cultured NK cells with cultured gammadelta T and alphabeta T cells that were prepared by conventional culture methods regarding the expression of cytotoxic molecules and cytotoxicity against cancer cells. Natural cytotoxicity receptors such as NKp30, NKp44 and NKp46, and perforin were expressed most exclusively on NK cells. Granzyme A, NKG2D, and interferon-gamma were dominantly expressed in NK cells and gammadelta T cells but not in alphabeta T cells. Consistent with the expression profiles of the cytotoxic molecules, cultured NK cells from both healthy volunteers and cancer patients demonstrated significantly higher cytotoxicity against cancer cell lines, including MHC class I-positive cell lines, compared with cultured gammadelta T cells and cultured alphabeta T cells. Additionally, NK cells, unlike gammadelta T cells or alphabeta T cells, expressed high levels of CD16, and showed augmented cytotoxicity when co administered with an anti-CD20 monoclonal antibody drug, rituximab. These results suggest the excellent efficacy of expanded NK cells for cancer treatment. PMID- 25131563 TI - Commercial sexual exploitation and sex trafficking of children in the United States. AB - Child commercial sexual exploitation and sex trafficking are global health problems requiring a multidisciplinary approach by individuals, organizations, communities, and national governments. The adverse emotional, physical, and social consequences for victims are legion and in many areas of the United States and the rest of the world, victim resources are scarce. Since violence, deprivation, abuse, and infection are so integral to the exploitation experience, victims may present for care to community and academic pediatric and adolescent health care providers. It is essential that medical professionals have the knowledge, skills, and resources to recognize victims, assess their needs, and treat them appropriately, including making key referrals for community services. However, to date medical information and resources regarding commercial sexual exploitation and sex trafficking has been sparse. There are no clinically validated screening tools specifically designed to identify victims in the health care setting and since victims seldom self-identify, it is likely that the majority of victims are unrecognized. The opportunity for comprehensive assessment and intervention is lost. Further, professionals receive little training on appropriate interview techniques for this special population, and many are ill equipped to ensure safety and optimal medical evaluation during the visit. This article provides a general overview of child sex trafficking and commercial sexual exploitation (CSEC), describing the epidemiology of international and domestic exploitation, and reviewing the challenges of conducting research on this population. The five stages of trafficking are explained, as are typical physical and emotional consequences of exploitation. The medical evaluation is described, including potential indicators of CSEC and sex trafficking, common medical presentations by victims, approaches to the comprehensive medical interview, and the appropriate medical exam with diagnostic testing and treatment. Finally, a discussion of common victim needs is provided, with a description of resources and referrals. PMID- 25131564 TI - Environmental contributors to autism: the pediatrician's role. PMID- 25131565 TI - Commentary: Commercial sexual exploitation--a survivor's perspective: "Can you help me? Do you care?". PMID- 25131562 TI - Cannabinoid modulation of alpha2 adrenergic receptor function in rodent medial prefrontal cortex. AB - Endocannabinoids acting at the cannabinoid type 1 receptor (CB1R) are known to regulate attention, cognition and mood. Previous studies have shown that, in the rat medial prefrontal cortex (mPFC), CB1R agonists increase norepinephrine release, an effect that may be attributed, in part, to CB1Rs localised to noradrenergic axon terminals. The present study was aimed at further characterising functional interactions between CB1R and adrenergic receptor (AR) systems in the mPFC using in vitro intracellular electrophysiology and high resolution neuroanatomical techniques. Whole-cell patch-clamp recordings of layer V/VI cortical pyramidal neurons in rats revealed that both acute and chronic treatment with the synthetic CB1R agonist WIN 55,212-2 blocked elevations in cortical pyramidal cell excitability and increases in input resistance evoked by the alpha2-adrenergic receptor (alpha2-AR) agonist clonidine, suggesting a desensitisation of alpha2-ARs. These CB1R-alpha2-AR interactions were further shown to be both action potential- and gamma-aminobutyric acid-independent. To better define sites of cannabinoid-AR interactions, we localised alpha2A adrenergic receptors (alpha2A-ARs) in a genetically modified mouse that expressed a hemoagglutinin (HA) tag downstream of the alpha2A-AR promoter. Light and electron microscopy indicated that HA-alpha2A-AR was distributed in axon terminals and somatodendritic processes especially in layer V of the mPFC. Triple labeling immunocytochemistry revealed that alpha2A-AR and CB1R were localised to processes that contained dopamine-beta-hydroxylase, a marker of norepinephrine. Furthermore, HA-alpha2A-AR was localised to processes that were directly apposed to CB1R. These findings suggest multiple sites of interaction between cortical cannabinoid-adrenergic systems that may contribute to understanding the effect of cannabinoids on executive functions and mood. PMID- 25131566 TI - Quality of life in caregivers of severely disabled war survivors. AB - PURPOSE: To evaluate quality of life (QOL) of caregivers of severely disabled war survivors and identify variables threatening caregivers' QOL. METHODS: A cross sectional study was performed on 532 caregivers of Iran-Iraq war related injured survivors by using Persian version of 36-item Short Form Health Survey (SF-36). FINDINGS: Caregivers had lower QOL compared to the Iranian female population (p < .001). Caregivers of amputees had better SF-36 scores compared to caregivers of two groups of chemical warfare survivors (p ranging from .01 to <.001). Caregiving to chemical warfare and being married at the time of trauma were the independent predictors of poor QOL in both the physical component summary (OR = 5.08, 95% CI = 3.35-7.7; OR = 0.57, 95% CI = 0.37-0.89) and the mental component summary (OR = 4.12, 95% CI = 2.68-6.32; OR = 0.63, 95% CI = 0.40-0.98). CONCLUSION AND CLINICAL RELEVANCE: Caregivers of war veterans suffer from poor QOL. Chemical warfare agents contribute to more persistent poor QOL in caregivers than the injuries caused by conventional weapons. PMID- 25131567 TI - Prehypertension in rural northeastern China: results from the northeast China rural cardiovascular health study. AB - This study aimed to determine the present status of prehypertension in rural China. It was conducted between January and August 2013, using a multistage clustering method to select a representative sample of individuals (>=35 years old), resulting in a study population of 11,576 adults. Prehypertension was defined as a systolic blood pressure (BP) in the range of 120 mm Hg to 139 mm Hg and/or a diastolic BP between 80 mm Hg and 89 mm Hg according to the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). The results showed that the mean+/ standard deviation systolic and diastolic BP values for the entire population were 141.8+/-23.5 mm Hg and 82.1+/-11.8 mm Hg, respectively. Among the whole population, 35.1% of men and 32.5% of women were prehypertensive. Multiple logistic regression analysis showed that high body mass index, advanced age, alcohol consumption, diabetes, high triglyceride and low-density lipoprotein cholesterol levels, and elevated diet score were risk factors for prehypertension. This study indicates that there is a high prevalence of prehypertension in rural China and confirms the importance of healthy lifestyles- including the control of obesity, diabetes, and dyslipidemia--to decrease the incidence of prehypertension. PMID- 25131569 TI - Negative poisson's ratio in single-layer black phosphorus. AB - The Poisson's ratio is a fundamental mechanical property that relates the resulting lateral strain to applied axial strain. Although this value can theoretically be negative, it is positive for nearly all materials, though negative values have been observed in so-called auxetic structures. However, nearly all auxetic materials are bulk materials whose microstructure has been specifically engineered to generate a negative Poisson's ratio. Here we report using first-principles calculations the existence of a negative Poisson's ratio in a single-layer, two-dimensional material, black phosphorus. In contrast to engineered bulk auxetics, this behaviour is intrinsic for single-layer black phosphorus, and originates from its puckered structure, where the pucker can be regarded as a re-entrant structure that is comprised of two coupled orthogonal hinges. As a result of this atomic structure, a negative Poisson's ratio is observed in the out-of-plane direction under uniaxial deformation in the direction parallel to the pucker. PMID- 25131568 TI - First description of scrotal testicles in a dog affected by 78, XX testicular disorder of sex development. AB - An eight-month-old female dog presented with ambiguous external genitalia. A thorough clinical examination together with various imaging techniques and a histology examination showed the presence of two testicles linked to both the Mullerian and Wolffian ducts. The discovery of the 78,XX SRY-negative karyotype led to the diagnosis of incoherence between the chromosomal and gonadal sex, which is typical for a 78,XX testicular disorder of sex development. Our case was unique because the testicles were still located in their normal scrotal position, whereas the literature contains reports of the presence of cryptorchid testicles in this karyotype setting. To our knowledge, this is the first case that describes an SRY-negative 78,XX testicular disorder of sex development with bilateral scrotal testicles. PMID- 25131570 TI - Overview of hepatitis B prevalence, prevention, and management in the Pacific Islands and Territories. AB - There are over 500-750 000 deaths per year because of hepatitis B virus (HBV) related cirrhosis and liver cancer worldwide and the World Health Organization Western Pacific Region has some of the highest endemic levels of HBV in the world, particularly within China, South East Asia and Pacific Island Countries and Territories (PICT). The PICT have unique ethnic diversity and a very high prevalence of smoking and metabolic syndrome, both important risk factors for liver fibrosis and liver cancer. However, in contrast to many Asian countries, there is little published data on HBV prevalence and related liver disease burden in PICT. In this review, the available published literature and World Health Organization data for HBV prevalence and related liver disease and liver cancer burden in PICT is outlined, and unmet needs for improving HBV prevention and control in the region are highlighted. PMID- 25131571 TI - Non-small cell lung cancer metastasis to the oral cavity: a case report. AB - Lung cancer, including non-small cell lung cancer, remains prevalent in Australia and has a very poor survival rate. Metastases to the oral cavity are a rare occurrence that can arise from lung cancers. This case report describes the presentation of a metastatic lesion from a poorly differentiated lung adenocarcinoma on the mandibular buccal alveolar attached gingivae. The inpatient had terminal disease with known pleural, brain and liver metastases and was receiving palliative care at the time of diagnosis of the oral lesion. PMID- 25131580 TI - Enhanced RBC Aggregation in Type 2 Diabetes Patients. AB - BACKGROUND: This study aimed to investigate the relationship between HbA1c and RBC aggregation in type 2 diabetes mellitus (T2DM) patients by analysis of data from routine clinical tests and from in vitro experiments. METHODS: A total of 2,111 inpatients with type 2 diabetes were selected and among them, 364 patients (Group A) had limited influence of plasma proteins on erythrocyte sedimentation rate (ESR) and was compared with the rest of the 1,747 inpatients (Group B). ESR, HbA1c , WBC, CRP, Fbg, and HCT were measured in all samples. Sixty samples were also collected from T2DM patients and used for in vitro ESR studies. Spearman's correlation coefficients were employed to reflect the correlation between ESR and other parameters. Mann-Whitney U test was used to compare the study parameters. RESULTS: The test results for Group A were lower than Group B with respect to ESR, age, HCT, HbA1c , CRP, WBC, and Fbg. Only the difference in HbA1c , CRP, and Fbg values had statistical significance (P < 0.05). In addition, HbA1c correlated better with ESR for Group A (R = 0.622) than Group B (R = 0.563), whereas CRP and Fbg were contrary to this. In the in vitro studies, the HbA1c values were classified into the subgroups of 6.5-8.0%, 8.1-10%, and >10%. The corresponding ESR values were 28 +/- 5.1 mm/h, 33 +/- 2.7 mm/h, and 40 +/- 4.1 mm/h, respectively. CONCLUSION: ESR results of T2DM patients were elevated that was mainly caused by Fbg levels, and in addition HbA1c in part contributed to RBC aggregation. PMID- 25131581 TI - Extensive structural rearrangements upon reduction of 9H-9-borafluorene. AB - Common wisdom has it that organoboranes are readily oxidized. Described herein is that also their reduction can result in remarkable chemistry. Treatment of dimeric 9H-9-borafluorene with Li metal in toluene yields two strikingly different classes of compounds. One part of the sample reacts in a way similar to B2H6, thus affording an aryl(hydro)borane cluster reminiscent of the [B3H8](-) anion. The other part furnishes a dianionic boron-doped graphene flake devoid of hydrogen substituents at the boron centers and featuring a central B=B bond. A change in the solvent to THF allows an isolation of this dibenzo[g,p]chrysene analogue in good yields. PMID- 25131583 TI - Amyloid structure. AB - Amyloid fibrils are formed by numerous proteins and peptides that share little sequence homology. The structures formed are highly ordered and extremely stable, being composed of beta-sheet structure and stabilized along their length by hydrogen bonding. The fibrils are formed by several protofilaments that wind around one another in rope-like structures, lending further strength and stability to the resulting fibres. The fact that so many proteins and peptides form amyloid structures under suitable conditions, seems to suggest that the sequence of the precursor is unimportant. However, it is now clear that side chains play a central role in forming interactions between several beta-sheets to further stabilize and regulate the structures. The primary sequence plays a central role in determining the rate of fibril formation, the stability of the resulting structure to degradation and the final morphology of the fibrils. The side chains regulate the elongation and growth, and also the lateral association of the protofilament and fibrils, having a significant impact on the final architecture. PMID- 25131584 TI - The physical chemistry of the amyloid phenomenon: thermodynamics and kinetics of filamentous protein aggregation. AB - In this chapter, we present an overview of the kinetics and thermodynamics of protein aggregation into amyloid fibrils. The perspective we adopt is largely experimental, but we also discuss recent developments in data analysis and we show that only a combination of well-designed experiments with appropriate theoretical modelling is able to provide detailed mechanistic insight into the complex pathways of amyloid formation. In the first part of the chapter, we describe measurements of the thermodynamic stability of the amyloid state with respect to the soluble state of proteins, as well as the magnitude and origin of this stability. In the second part, we discuss in detail the kinetics of the individual molecular steps in the overall mechanism of the conversion of soluble protein into amyloid fibrils. Finally, we highlight the effects of external factors, such as salt type and concentration, chemical denaturants and molecular chaperones on the kinetics of aggregation. PMID- 25131585 TI - Predicting aggregation-prone sequences in proteins. AB - Owing to its association with a diverse range of human diseases, the determinants of protein aggregation are studied intensively. It is generally accepted that the effective aggregation tendency of a protein depends on many factors such as folding efficiency towards the native state, thermodynamic stability of that conformation, intrinsic aggregation propensity of the polypeptide sequence and its ability to be recognized by the protein quality control system. The intrinsic aggregation propensity of a polypeptide sequence is related to the presence of short APRs (aggregation-prone regions) that self-associate to form intermolecular beta-structured assemblies. These are typically short sequence segments (5-15 amino acids) that display high hydrophobicity, low net charge and a high tendency to form beta-structures. As the presence of such APRs is a prerequisite for aggregation, a plethora of methods have been developed to identify APRs in amino acid sequences. In the present chapter, the methodological basis of these approaches is discussed, as well as some practical applications. PMID- 25131582 TI - Genetic analysis of colon tumors induced by a dietary carcinogen PhIP in CYP1A humanized mice: Identification of mutation of beta-catenin/Ctnnb1 as the driver gene for the carcinogenesis. AB - Replacing mouse Cyp1a with human CYP1A enables the humanized CYP1A mice to mimic human metabolism of the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP), by N(2) -hydroxylation to a proximate carcinogen. Our previous study demonstrated that PhIP, combined with the dextrin sulfate sodium (DSS) induced colitis, induces colon carcinogenesis in hCYP1A mice. Here, we employed whole exome sequencing and found multiple gene mutations in PhIP/DSS-induced colon tumors. Mutations in the exon 3 of Ctnnb1/beta-catenin, however, were the predominant events. We further sequenced the key fragments of Apc, Ctnnb1, and Kras, because mutations of these genes in the humans are commonly found as the drivers of colorectal cancer. Mutations on either codon 32 or 34 in the exon 3 of Ctnnb1 were found in 39 out of 42 tumors, but no mutation was found in either Apc or Kras. The sequence context of codons 32 and 34 suggests that PhIP targets +3G in a TGGA motif of Ctnnb1. Since mutations that activate Wnt signal is a major driving force for human colorectal cancers, we conclude that the mutated beta catenin is the driver in PhIP/DSS-induced colon carcinogenesis. This result suggests that the colon tumors in hCYP1A mice mimic human colorectal carcinogenesis not only in the dietary etiology involving PhIP, but also in the aberrant activation of the Wnt signaling pathway as the driving force. PMID- 25131586 TI - Protein folding, misfolding and quality control: the role of molecular chaperones. AB - Cells have to cope with stressful conditions and adapt to changing environments. Heat stress, heavy metal ions or UV stress induce damage to cellular proteins and disturb the balanced status of the proteome. The adjusted balance between folded and folding proteins, called protein homoeostasis, is required for every aspect of cellular functionality. Protective proteins called chaperones are expressed under extreme conditions in order to prevent aggregation of cellular proteins and safeguard protein quality. These chaperones co-operate during de novo folding, refolding and disaggregation of damaged proteins and in many cases refold them to their functional state. Even under physiological conditions these machines support protein homoeostasis and maintain the balance between de novo folding and degradation. Mutations generating unstable proteins, which are observed in numerous human diseases such as Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis and cystic fibrosis, also challenge the protein quality control system. A better knowledge of how the protein homoeostasis system is regulated will lead to an improved understanding of these diseases and provide potential targets for therapy. PMID- 25131587 TI - Insights into amyloid disease from fly models. AB - The formation of amyloid aggregates is a feature of most, if not all, polypeptide chains. In vivo modelling of this process has been undertaken in the fruitfly Drosophila melanogaster with remarkable success. Models of both neurological and systemic amyloid diseases have been generated and have informed our understanding of disease pathogenesis in two main ways. First, the toxic amyloid species have been at least partially characterized, for example in the case of the Abeta (amyloid beta-peptide) associated with Alzheimer's disease. Secondly, the genetic underpinning of model disease-linked phenotypes has been characterized for a number of neurodegenerative disorders. The current challenge is to integrate our understanding of disease-linked processes in the fly with our growing knowledge of human disease, for the benefit of patients. PMID- 25131588 TI - Yeast models for amyloid disease. AB - Saccharomyces cerevisiae (baker's yeast) is a well-established eukaryotic model organism, which has significantly contributed to our understanding of mechanisms that drive numerous core cellular processes in higher eukaryotes. Moreover, this has led to a greater understanding of the underlying pathobiology associated with disease in humans. This tractable model offers an abundance of analytical capabilities, including a vast array of global genetics and molecular resources that allow genome-wide screening to be carried out relatively simply and cheaply. A prime example of the versatility and potential for applying yeast technologies to explore a mammalian disease is in the development of yeast models for amyloid diseases such as Alzheimer's, Parkinson's and Huntington's. The present chapter provides a broad overview of high profile human neurodegenerative diseases that have been modelled in yeast. We focus on some of the most recent findings that have been developed through genetic and drug screening studies using yeast genomic resources. Although this relatively simple unicellular eukaryote seems far removed from relatively complex multicellular organisms such as mammals, the conserved mechanisms for how amyloid exhibits toxicity clearly underscore the value of carrying out such studies in yeast. PMID- 25131589 TI - Amyloid beta-peptide and Alzheimer's disease. AB - One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Abeta (amyloid beta peptide). According to the 'amyloid cascade' hypothesis, the aggregation of Abeta initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Abeta and towards smaller and more soluble 'oligomers' as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Abeta from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Abeta, which is still the main hope for providing a more effective treatment for AD in the future. PMID- 25131590 TI - The physiology and pathology of microtubule-associated protein tau. AB - Tau belongs to the family of microtubule-associated proteins predominantly expressed in neurons where they play an important role in promoting microtubule assembly and stabilizing microtubules. In addition, tau proteins interact with other cytoskeletal elements to allow spacing between microtubules. Recent studies have shown that tau is also actively involved in regulating cell viability and activity. Translated from a single gene located on chromosome 17q21, six isoforms of tau are produced by alternative splicing in adult human brain. Due to multiple post-translational modifications, heterogeneous tau species with a wide range of apparent molecular masses have been observed by denaturing polyacrylamide-gel electrophoresis. Since tau gene mutations and abnormal post-translational modifications have been detected in over 20 neurodegenerative disorders, namely the tauopathies, tau has gained widespread attention as a target protein in Alzheimer's disease and other neurodegenerative disorders. In the present chapter, research progress regarding physiology and pathology of tau is reviewed, particularly in terms of the role of post-translational modification. PMID- 25131591 TI - Role of alpha-synuclein in neurodegeneration: implications for the pathogenesis of Parkinson's disease. AB - alpha-Syn (alpha-synuclein) is a small soluble acidic protein that is extensively expressed in the nervous system. Genetic, clinical and experimental studies demonstrate that alpha-syn is strongly implicated in the pathogenesis of PD (Parkinson's disease). However, the pathogenic mechanism remains elusive. In the present chapter, we first describe the normal expression and potential physiological functions of alpha-syn. Then, we introduce recent research progress related to the pathogenic role of alpha-syn in PD, with special emphasis on how alpha-syn oligomers cause the preferential degeneration of dopaminergic neurons in the substantia nigra and the spreading of alpha-syn pathology in the brain of PD patients. PMID- 25131592 TI - Oligomers of alpha-synuclein: picking the culprit in the line-up. AB - In the present chapter, we discuss the key findings on alphasyn (alpha-synuclein) oligomers from a biophysical point of view. Current structural methods cannot provide a high-resolution structure of alphasyn oligomers due to their size, heterogeneity and tendency to aggregate. However, a low-resolution structure of a stable alphasyn oligomer population is emerging based on compelling data from different research groups. alphasyn oligomers are normally observed during the formation of amyloid fibrils and we discuss how they are connected to this process. Another important topic is the interaction of alphasyn oligomers and membranes, and we will discuss the evidence which suggests that this interaction might be essential in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. Finally, we present a remarkable example of how small molecules are able to stabilize non-amyloid oligomers and how this might be a potential strategy to inhibit the inherent toxicity of alphasyn oligomers. A major challenge is to link the very complex oligomerization pathways seen in clever experiments in vitro with what actually happens in the cell. With the tremendous developments in optical microscopy in mind, we believe that it will be possible to make this link very soon. PMID- 25131593 TI - Many roads lead to Rome? Multiple modes of Cu,Zn superoxide dismutase destabilization, misfolding and aggregation in amyotrophic lateral sclerosis. AB - ALS (amyotrophic lateral sclerosis) is a fatal neurodegenerative syndrome characterized by progressive paralysis and motor neuron death. Although the pathological mechanisms that cause ALS remain unclear, accumulating evidence supports that ALS is a protein misfolding disorder. Mutations in Cu,Zn-SOD1 (copper/zinc superoxide dismutase 1) are a common cause of familial ALS. They have complex effects on different forms of SOD1, but generally destabilize the protein and enhance various modes of misfolding and aggregation. In addition, there is some evidence that destabilized covalently modified wild-type SOD1 may be involved in disease. Among the multitude of misfolded/aggregated species observed for SOD1, multiple species may impair various cellular components at different disease stages. Newly developed antibodies that recognize different structural features of SOD1 represent a powerful tool for further unravelling the roles of different SOD1 structures in disease. Evidence for similar cellular targets of misfolded/aggregated proteins, loss of cellular proteostasis and cell cell transmission of aggregates point to common pathological mechanisms between ALS and other misfolding diseases, such as Alzheimer's, Parkinson's and prion diseases, as well as serpinopathies. The recent progress in understanding the molecular basis for these devastating diseases provides numerous avenues for developing urgently needed therapeutics. PMID- 25131595 TI - Prion disease and the 'protein-only hypothesis'. AB - Prion disease is the only naturally occurring infectious protein misfolding disorder. The chemical nature of the infectious agent has been debated for more than half a century. Early studies on scrapie suggested that the unusual infectious agent might propagate in the absence of nucleic acid. The 'protein only hypothesis' provides a theoretical model to explain how a protein self replicates without nucleic acid, which predicts that a prion, the proteinaceous infectious agent, propagates by converting its normal counterpart into the likeness of itself. Decades of studies have provided overwhelming evidence to support this hypothesis. The latest advances in generating infectious prions with bacterially expressed recombinant prion protein in the presence of cofactors not only provide convincing evidence supporting the 'protein-only hypothesis', but also indicate a role of cofactors in forming prion infectivity and encoding prion strains. In the present chapter, we review the literature regarding the chemical nature of the infectious agent, describe recent achievements in proving the 'protein-only hypothesis', and discuss the remaining questions in this research area. PMID- 25131594 TI - Spontaneous self-assembly of pathogenic huntingtin exon 1 protein into amyloid structures. AB - PolyQ (polyglutamine) diseases such as HD (Huntington's disease) or SCA1 (spinocerebellar ataxia type 1) are neurodegenerative disorders caused by abnormally elongated polyQ tracts in human proteins. PolyQ expansions promote misfolding and aggregation of disease-causing proteins, leading to the appearance of nuclear and cytoplasmic inclusion bodies in patient neurons. Several lines of experimental evidence indicate that this process is critical for disease pathogenesis. However, the molecular mechanisms underlying spontaneous polyQ containing aggregate formation and the perturbation of neuronal processes are still largely unclear. The present chapter reviews the current literature regarding misfolding and aggregation of polyQ-containing disease proteins. We specifically focus on studies that have investigated the amyloidogenesis of polyQ containing HTTex1 (huntingtin exon 1) fragments. These protein fragments are disease-relevant and play a critical role in HD pathogenesis. We outline potential mechanisms behind mutant HTTex1 aggregation and toxicity, as well as proteins and small molecules that can modify HTTex1 amyloidogenesis in vitro and in vivo. The potential implications of such studies for the development of novel therapeutic strategies are discussed. PMID- 25131596 TI - Amyloid diseases of yeast: prions are proteins acting as genes. AB - The unusual genetic properties of the non-chromosomal genetic elements [URE3] and [PSI+] led to them being identified as prions (infectious proteins) of Ure2p and Sup35p respectively. Ure2p and Sup35p, and now several other proteins, can form amyloid, a linear ordered polymer of protein monomers, with a part of each molecule, the prion domain, forming the core of this beta-sheet structure. Amyloid filaments passed to a new cell seed the conversion of the normal form of the protein into the same amyloid form. The cell's phenotype is affected, usually from the deficiency of the normal form of the protein. Solid-state NMR studies indicate that the yeast prion amyloids are in-register parallel beta-sheet structures, in which each residue (e.g. Asn35) forms a row along the filament long axis. The favourable interactions possible for aligned identical hydrophilic and hydrophobic residues are believed to be the mechanism for propagation of amyloid conformation. Thus, just as DNA mediates inheritance by templating its own sequence, these proteins act as genes by templating their conformation. Distinct isolates of a given prion have different biological properties, presumably determined by differences between the amyloid structures. Many lines of evidence indicate that the Saccharomyces cerevisiae prions are pathological disease agents, although the example of the [Het-s] prion of Podospora anserina shows that a prion can have beneficial aspects. PMID- 25131597 TI - Functional amyloid: widespread in Nature, diverse in purpose. AB - Amyloids are insoluble fibrillar protein deposits with an underlying cross-beta structure initially discovered in the context of human diseases. However, it is now clear that the same fibrillar structure is used by many organisms, from bacteria to humans, in order to achieve a diverse range of biological functions. These functions include structure and protection (e.g. curli and chorion proteins, and insect and spider silk proteins), aiding interface transitions and cell-cell recognition (e.g. chaplins, rodlins and hydrophobins), protein control and storage (e.g. Microcin E492, modulins and PMEL), and epigenetic inheritance and memory [e.g. Sup35, Ure2p, HET-s and CPEB (cytoplasmic polyadenylation element-binding protein)]. As more examples of functional amyloid come to light, the list of roles associated with functional amyloids has continued to expand. More recently, amyloids have also been implicated in signal transduction [e.g. RIP1/RIP3 (receptor-interacting protein)] and perhaps in host defence [e.g. aDrs (anionic dermaseptin) peptide]. The present chapter discusses in detail functional amyloids that are used in Nature by micro-organisms, non-mammalian animals and mammals, including the biological roles that they play, their molecular composition and how they assemble, as well as the coping strategies that organisms have evolved to avoid the potential toxicity of functional amyloid. PMID- 25131598 TI - Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms. AB - BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of AAA rupture. AAA peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether AAA PWS can predict AAA rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact AAA. METHODS: The MEDLINE database was searched on 25 May 2013. Case-control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. RESULTS: Nine studies assessing 348 individuals were identified and used in the meta analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured AAAs showed that PWS was significantly greater in the symptomatic/ ruptured AAAs compared with the asymptomatic intact AAAs (SMD 0.95, 95 per cent confidence interval 0.71 to 1.18; P < 0.001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0.68, 0.39 to 0.96; P < 0.001). Minimal heterogeneity between studies was noted (I(2) = 0 per cent). CONCLUSION: This study suggests that PWS is greater in symptomatic or ruptured AAA than in asymptomatic intact AAA. PMID- 25131599 TI - Prostaglandin E2 as a read out for endotoxin detection in a bovine whole blood assay. AB - The detection of endotoxin contamination is an essential part of drug safety testing. The rabbit pyrogen test (RPT), the limulus amoebocyte lysate (LAL) test, and the monocyte activation test (MAT) are established methods for the detection of pyrogens. However, the RPT is insufficiently standardized; the LAL test is solely capable of identifying the presence of endotoxins, whereas the use of the MAT is limited by the availability of human blood. Here, we introduce a new procedure for testing endotoxin contamination using prostaglandin E2 (PGE2 ) release from bovine whole blood. We incubated bovine whole blood overnight with lipopolysaccharide (LPS) from Escherichia coli 0111:B4, concentrations ranging from 1.56 to 12.5 pg/mL, and found significantly increased PGE2 production for even the lowest LPS concentrations. Testing the possibility of storing the blood at 4 degrees C before use also yielded positive results as 1.56 pg/mL still significantly increased PGE2 production, thus suggesting some flexibility of the assay regarding time. These results emphasize the potential of using bovine whole blood for highly sensitive endotoxin testing. As a perspective, currently ongoing research aims to show whether the assay is also capable of detecting nonendotoxin pyrogens. PMID- 25131600 TI - Dietary total antioxidant capacity is associated with leukocyte telomere length in a children and adolescent population. AB - BACKGROUND & AIMS: Oxidative stress and inflammation seem to be potential underlying mechanisms for telomere attrition. A lack of specific antioxidants is believed to increase free radical damage and a greater risk for telomere shortening. Our aim was to evaluate the relationship between diet and leukocyte telomere length in a cross-sectional study of children and adolescents. We hypothesized that dietary total antioxidant capacity would be positively associated with telomere length. METHODS: Telomere length was measured by quantitative real-time polymerase chain reaction in 287 participants (55% males, 6-18 years), who were randomly selected from the GENOI study. RESULTS: A positive correlation between dietary total antioxidant capacity and telomere length (r = 0.157, p = 0.007) was found after adjustment for age and energy intake. However, higher white bread consumption was associated with shorter telomeres (beta = 0.204, p = 0.002) in fully-adjusted models. Interestingly, those individuals who had simultaneously higher dietary total antioxidant capacity and lower white bread consumption significantly presented the longest telomeres. Moreover, the multivariable-adjusted odds ratio for very short telomeres was 0.30 for dietary total antioxidant capacity (p = 0.023) and 1.37 for white bread (p = 0.025). CONCLUSION: It was concluded that longer telomeres were associated with higher dietary total antioxidant capacity and lower white bread consumption in Spanish children and adolescents. These findings might open a new line of investigation about the potential role of an antioxidant diet in maintaining telomere length. PMID- 25131601 TI - Routes for early enteral nutrition after esophagectomy. A systematic review. AB - BACKGROUND: Early enteral feeding following surgery can be given orally, via a jejunostomy or via a nasojejunal tube. However, the best feeding route following esophagectomy is unclear. OBJECTIVES: To determine the best route for enteral nutrition following esophagectomy regarding anastomotic leakage, pneumonia, percentage meeting the nutritional requirements, weight loss, complications of tube feeding, mortality, patient satisfaction and length of hospital stay. DESIGN: A systematic literature review following PRISMA and MOOSE guidelines. RESULTS: There were 17 eligible studies on early oral intake, jejunostomy or nasojejunal tube feeding. Only one nonrandomized study (N = 133) investigated early oral feeding specifically following esophagectomy. Early oral feeding was associated with a reduced length of stay with delayed oral feeding, without increased complication rates. Postoperative nasojejunal tube feeding was not significantly different from jejunostomy tube feeding regarding complications or catheter efficacy in the only randomised trial on this subject (N = 150). Jejunostomy tube feeding outcome was reported in 12 non-comparative studies (N = 3293). It was effective in meeting short-term nutritional requirements, but major tube-related complications necessitated relaparotomy in 0-2.9% of patients. In three non-comparative studies (N = 135) on nasojejunal tube feeding only minor complications were reported, data on nutritional outcome was lacking. Data on patient satisfaction and long-term nutritional outcome were not found for any of the feeding routes investigated. CONCLUSION: It is unclear what the best route for early enteral nutrition is after esophagectomy. Especially data regarding early oral intake are scarce, and phase 2 trials are needed for further investigation. REGISTRATION: International prospective register of systematic reviews, CRD42013004032. PMID- 25131603 TI - Gender differences in perceived stigma of dementia in Chinese Americans. PMID- 25131602 TI - Changes of hepatic lipid mediators associated with intake of high-fat diet for 12 weeks in endotoxemic rats using LC-ESI-MS/MS. AB - BACKGROUND & AIMS: It has recently been reported that anti-inflammatory lipid mediators are increased in the late phase of acute inflammation, whereas proinflammatory lipid mediators are regulated at the initiation of inflammation. The purpose of this study was to evaluate changes of hepatic lipid mediators due to high-fat diet (HFD) feeding in endotoxemic rats. METHODS: Male Wistar rats were fed either HFD or control diet for 12 weeks, and were then killed 0, 1.5, and 6 h after lipopolysaccharide (LPS) injection. Analyses included lipidomics assessment of mediators using liquid chromatography-electrospray ionization/multi stage mass spectrometry; measuring expression of hepatic polyunsaturated fatty acid (PUFA)-oxidizing enzyme, tumor necrosis factor (TNF)-alpha, interleukin (IL) 6, and inducible nitric oxide synthase mRNA levels; blood biochemical tests; and liver histology. RESULTS: HFD feeding worsened liver injury, increased expression of TNF-alpha and IL-6 mRNA, and increased oxidative stress after LPS injection. PUFA-oxidizing enzymes were higher in HFD-fed rats after LPS injection. The proinflammatory prostaglandin (PG)E2 and thromboxane B2 were increased 1.5 h after LPS injection, and had decreased by 6 h in HFD-fed rats. In contrast, potent pro-resolving resolvins derived from eicosapentaenoic acid and docosahexaenoic acid were not detected, but anti-inflammatory epoxyeicosatrienoic acids, lipoxin A4, and 15-deoxy-PGJ2 were increased after LPS injection in HFD fed rats. CONCLUSIONS: HFD feeding for 12 weeks enhanced proinflammatory lipid mediators 1.5 h after LPS injection suggesting relation to liver injury. PMID- 25131604 TI - Depression, anxiety, and memory impairment among geriatric inpatient subjects. PMID- 25131606 TI - Nurses are essential players in all health and policy arenas. PMID- 25131607 TI - Ethical dilemmas: the challenge of advocating for human rights. PMID- 25131608 TI - The power of unity. PMID- 25131610 TI - C. pneumoniae disrupts eNOS trafficking and impairs NO production in human aortic endothelial cells. AB - Endothelial nitric oxide synthase (eNOS) generated NO plays a crucial physiological role in the regulation of vascular tone. eNOS is a constitutively expressed synthase whose enzymatic function is regulated by dual acylation, phosphorylation, protein-protein interaction and subcellular localization. In endothelial cells, the enzyme is primarily localized to the Golgi apparatus (GA) and the plasma membrane where it binds to caveolin-1. Upon stimulation, the enzyme is translocated from the plasma membrane to the cytoplasm where it generates NO. When activation of eNOS ceases, the majority of the enzyme is recycled back to the membrane fraction. An inability of eNOS to cycle between the cytosol and the membrane leads to impaired NO production and vascular dysfunction. Chlamydia pneumoniae is a Gram-negative obligate intracellular bacterium that primarily infects epithelial cells of the human respiratory tract, but unlike any other chlamydial species, C. pneumoniae displays tropism toward atherosclerotic tissues. In this study, we demonstrate that C. pneumoniae inclusions colocalize with eNOS, and the microorganism interferes with trafficking of the enzyme from the GA to the plasma membrane in primary human aortic endothelial cells. This mislocation of eNOS results in significant inhibition of NO release by C. pneumoniae-infected cells. Furthermore, we show that the distribution of eNOS in C. pneumoniae-infected cells is altered due to an intimate association of the Golgi complex with chlamydial inclusions rather than by direct interaction of the enzyme with the chlamydial inclusion membrane. PMID- 25131605 TI - The safe passage study: design, methods, recruitment, and follow-up approach. AB - BACKGROUND: The Safe Passage Study is a large, prospective, multidisciplinary study designed to (1) investigate the association between prenatal alcohol exposure, sudden infant death syndrome (SIDS), and stillbirth, and (2) determine the biological basis of the spectrum of phenotypic outcomes from exposure, as modified by environmental and genetic factors that increase the risk of stillbirth, SIDS, and in surviving children, fetal alcohol spectrum disorders. METHODS: The results provided are based on an interim assessment of 6004 women enrolled, out of the 12,000 projected, from the Northern Plains, US, and Cape Town, South Africa, areas known to be of high risk for maternal drinking during pregnancy. Research objectives, study design, and descriptive statistics, including consent, recruitment, and retention information, are provided. RESULTS: Overall visit compliance is 87%, and includes prenatal, delivery/newborn, and postnatal contacts through 1 year post-delivery. Pregnancy outcome ascertainment is 98% prior to medical chart review; less than 2% of women withdraw. Consent for the use of DNA and placental tissue exceed 94%, and consent to participate in the autopsy portion of the study is 71%. CONCLUSIONS: The Safe Passage Study is the first multi-site study of SIDS and stillbirth to integrate prospectively collected exposure information with multidisciplinary biological information in the same maternal and fetal/infant dyad using a common protocol. Essential components of the study design and its success are close ties to the community and rigorous systems and processes to ensure compliance with the study protocol and procedures. PMID- 25131611 TI - Potential efficacy of dopamine loaded-PVP/PAA nanogel in experimental models of Parkinsonism: possible disease modifying activity. AB - This study aimed to investigate the ability of dopamine (DA)-loaded polyvinylpyrrolidone-poly(acrylic acid) (PVP/PAAc) nanogel [synthesized by gamma (gamma) radiation-induced template polymerization] [Nano-DA] to deliver DA across the blood brain barrier, and to evaluate the efficacy and safety of the acute and subchronic administration of Nano-DA in modulating motor activity and/or the biochemical changes in rat brain; induced by different models of Parkinsonism. In this respect, (PVP/PAAc) nanogel was synthesized by gamma radiation-induced polymerization of acrylic acid (AAc) in an aqueous solution of PVP as a template polymer, and then, it was used as a nano-drug carrier for DA. The PVP/PAAc and (PVP/PAAc loaded-DA nanogel particles were characterized by dynamic light scattering, infrared spectroscopy, and field emission-scanning electron microscopy. The loaded gel was administered in different doses and dosing regimens to Parkinsonian rats, and the catalepsy score and striatal DA levels were assessed. Then, the potential disease-modifying activity of this form of DA was investigated, through the assessment of the improvement in mitochondrial function, following the subchronic administration of Nano-DA to Parkinsonian rats. Significant disease-modifying effects were observed upon the administration of Nano-DA; in addition to normalization in their motor activity. PMID- 25131613 TI - Thoracic manifestations of connective tissue diseases. AB - Connective tissue diseases (CTDs) comprise several immunologic systemic disorders, each of which associated with a particular set of clinical manifestations and autoimmune profile. CTDs may cause numerous thoracic abnormalities, which vary in frequency and pattern according to the underlying disorder. The CTDs that most commonly involve the respiratory system are progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, polymyositis, dermatomyositis, and mixed connective tissue disease. Pulmonary abnormalities in this group of patients may result from CTD-related lung disease or treatment complications, namely drug toxicity and opportunistic infections. The most important thoracic manifestations of CTDs are interstitial lung disease and pulmonary arterial hypertension, with nonspecific interstitial pneumonia being the most common pattern of interstitial lung disease. High-resolution computed tomography is a valuable tool in the initial evaluation and follow-up of patients with CTDs. As such, general knowledge of the most common high-resolution computed tomographic features of CTD-related lung disease allows the radiologist to contribute to better patient management. PMID- 25131614 TI - Coprinopsis atramentaria extract, its organic acids, and synthesized glucuronated and methylated derivatives as antibacterial and antifungal agents. AB - Despite the available data regarding antimicrobial activity of phenolic acids, studies dealing with the effects of their metabolites or derivatives are scarce. Therefore, the antimicrobial and demelanizing activities of Coprinopsis atramentaria extract, its organic acids, and methylated and glucuronated derivatives were evaluated. The antifungal activity was stronger than the antibacterial effects. In general, individual compounds (mostly organic acids) exhibited higher activity than the extract and even higher than the standards used in the assays. Methylated derivatives presented the highest demelanizing activity toward Aspergillus niger, A. fumigatus and Penicillium verrucosum var. cyclopium. The inclusion of methyl groups in the parental compound (CoAM1, CoAM2 and CoAM3) strongly increased antibacterial and antifungal activities of CoA, while the inclusion of acetyl groups (CoAGP) increased the antifungal activity but the antibacterial properties were maintained. For HA and CA, the inclusion of methyl groups (HAM1, HAM2, HAM3 and CAM) increased the demelanizing activity, but decreased the antimicrobial properties. The present work contributes to the knowledge of the mechanisms involved in the antimicrobial properties of organic acids namely, phenolic acids, usually present in mushrooms. Organic acids, and methylated and glucuronated derivatives could be used as antimicrobial agents. PMID- 25131615 TI - Molecular characteristics of Staphylococcus aureus associated with chronic rhinosinusitis. AB - The anterior nares have been regarded as the major carriage site of Staphylococcus aureus. From here, the organism can spread to other parts of the body where it might act as harmless commensal or cause mild to severe infections. Nasal sinuses are normally sterile, but in patients with chronic rhinosinusitis (CRS), the finding of S. aureus in maxillary sinus cultures is common. Isolates were obtained from the nares and maxillary sinus of patients with CRS and the nares of healthy controls. A significantly higher frequency of S. aureus was found in nares samples from patients (24/42) compared to controls (16/57) (p = 0.004). There is no consensus regarding whether S. aureus is a relevant pathogen in CRS. A DNA microarray was used to investigate the prevalence of S. aureus virulence genes with focus on staphylococcal enterotoxins, toxic shock syndrome toxin-1, agr types, and cell wall-associated proteins. The genotyping of S. aureus isolates revealed only small and non-significant differences in gene prevalence between isolates collected from patients with CRS and those collected from healthy nasal carriers. This study provides an increased knowledge of the genetic pattern of virulence genes among S. aureus collected in CRS. PMID- 25131612 TI - Blockade of 2-arachidonoylglycerol hydrolysis produces antidepressant-like effects and enhances adult hippocampal neurogenesis and synaptic plasticity. AB - The endocannabinoid ligand 2-arachidonoylglycerol (2-AG) is inactivated primarily by monoacylglycerol lipase (MAGL). We have shown recently that chronic treatments with MAGL inhibitor JZL184 produce antidepressant- and anxiolytic-like effects in a chronic unpredictable stress (CUS) model of depression in mice. However, the underlying mechanisms remain poorly understood. Adult hippocampal neurogenesis has been implicated in animal models of anxiety and depression and behavioral effects of antidepressants. We tested whether CUS and chronic JZL184 treatments affected adult neurogenesis and synaptic plasticity in the dentate gyrus (DG) of mouse hippocampus. We report that CUS induced depressive-like behaviors and decreased the number of bromodeoxyuridine-labeled neural progenitor cells and doublecortin-positive immature neurons in the DG, while chronic JZL184 treatments prevented these behavioral and cellular deficits. We also investigated the effects of CUS and chronic JZL184 on a form long-term potentiation (LTP) in the DG known to be neurogenesis-dependent. CUS impaired LTP induction, whereas chronic JZL184 treatments restored LTP in CUS-exposed mice. These results suggest that enhanced adult neurogenesis and long-term synaptic plasticity in the DG of the hippocampus might contribute to antidepressant- and anxiolytic-like behavioral effects of JZL184. PMID- 25131616 TI - Connections of the limbic network: a corticocortical evoked potentials study. AB - Papez proposed a network for higher brain function, which is termed the limbic network. However, the in vivo human limbic network has not been established. We investigated the connectivity of the human limbic system using corticocortical evoked potential (CCEP). This retrospective analysis included 28 patients with medically intractable focal epilepsy who underwent stereoelectroencephalography (SEEG) and CCEP. Alternating 1 Hz electrical stimuli were delivered to parts of the limbic system [anterior and posterior hippocampus, temporal pole, parahippocampal gyrus (PHG), amygdala, anterior (ACG) and posterior cingulate gyrus (PCG), medial and lateral orbitofrontal cortex (OF)]. A total of 40-60 stimuli were averaged in each trial to obtain CCEP responses. CCEP distributions were evaluated by calculating the root mean square (RMS) of CCEP responses. Anterior hippocampal stimulation elicited prominent CCEP responses in medial and lateral temporal structures, PCG, medial OF and insula over the ipsilateral hemisphere. Posterior hippocampal stimulation induced CCEP responses in the ipsilateral medial and lateral temporal structures and PCG. The findings also revealed connections from temporal pole to the ipsilateral medial temporal structures, and connections from PHG to the ipsilateral hippocampus and PCG. The amygdala projected to broad areas including the ipsilateral medial and lateral temporal structures, medial and lateral frontal areas, the cingulate gyrus, insula and inferior parietal lobule. ACG and PCG showed connections to the ipsilateral medial fronto-parietal areas and connections to bilateral medial temporo-parieto-occipital and lateral parieto-occipital areas, respectively. Medial and lateral OF stimulation induced responses in the adjacent cortices. This study revealed that various regions within the limbic network are intimately connected in reverberating circuits and are linked to specific ipsilateral and contralateral regions, which may reflect distinct functional roles. PMID- 25131617 TI - Serum microRNA-124 is a novel biomarker for liver necroinflammation in patients with chronic hepatitis B virus infection. AB - Patients with chronic hepatitis B virus (HBV) infection and normal or mildly increased transaminases may have sustained significant liver damage, as verified by liver biopsy. However, no suitable noninvasive method exists for identifying liver necroinflammation in such patients. We aimed to investigate the power of microRNA-124 as a novel biomarker for liver necroinflammation. A total of 131 recruited patients with chronic HBV infection underwent liver biopsy for grading of necroinflammation (G) and staging of fibrosis (S). Thirty healthy individuals were included as controls (HCs). Serum microRNA-124 and microRNA-122 levels were measured using qRT-PCR. Forty-five patients from the study population receiving entecavir therapy were monitored for changes in serum microRNA-124 levels in association with improved liver histology. The capacity of serum microRNA-124 levels in discriminating the grade of liver necroinflammation was compared with alanine aminotransferase (ALT) with liver biopsy validation. Serum microRNA-124 levels were significantly higher in patients with chronic HBV infection than in HCs (P < 0.0001). Patients with considerable liver necroinflammation (G >= 2) had significantly higher serum miRNA-124 levels than those without or with mild necroinflammation (P < 0.0001). After 48 weeks of antiviral therapy, serum microRNA-124 levels considerably declined in 45 patients (P < 0.0001), which were associated with histological improvement. In patients with normal ALT and a serum HBV DNA load >10(4) copies/mL, receiver operating characteristic (ROC) curve of serum microRNA-124 levels yielded an area under ROC curve (AUC) of 0.840, with 58.3% sensitivity and 91.7% specificity in discriminating between moderate-to severe liver necroinflammation (G >= 2). PMID- 25131618 TI - Neuroproteomics in the auditory brainstem: candidate proteins for ultrafast and precise information processing. AB - In the mammalian auditory brainstem, the cochlear nuclear complex (CN) and the superior olivary complex (SOC) feature structural and functional specializations for ultrafast (<1 ms) and precise information processing. Their proteome, the basis for structure and function, has been rarely analyzed so far. Here we identified and quantified the protein profiles of three major auditory brainstem regions of adult rats, the CN, the SOC, and the inferior colliculus (IC). The rest of the brain served as a reference. Via label-free quantitative mass spectrometry and 2-D DIGE/MALDI-MS, we identified 584 and 297 proteins in the plasma membrane/synaptic vesicle proteome and the cytosolic proteome, respectively. 'Region-typical' proteins, i.e., those with higher abundance in one region than in the other three, were considered candidates for functional specializations. Key proteins were validated via Western blots and immunohistochemistry. Functional annotation clustering revealed an overrepresentation of neurofilament proteins among the CN+SOC-typical proteins. These are related to regulation of axon diameter and, thereby, conduction velocity. Interestingly, the sets of synapse-associated proteins differed between regions. For example, synaptotagmin-2 (Syt2), a Ca2+ sensor for fast exocytosis, was CN+SOC+IC-typical, whereas Syt1 was CN+SOC+IC-atypical. Together, our quantitative comparison of protein profiles has revealed several interesting candidate proteins for ultrafast and precise information processing. PMID- 25131620 TI - Pilot study to assess measures to be used in the prospective audit of the management of foot ulcers in people with diabetes. AB - AIM: To design and test a methodology for assessing aspects of the management of foot disease in diabetes. METHODS: A national working group devised pilot datasets that may be used to document the process of management of active ulceration. Participating volunteer specialist units throughout England were required to characterize newly presenting people with diabetic foot ulcers using a standard questionnaire comprising the dataset and to document outcomes at 6 and 12 months. Semi-structured interviews were later conducted with the volunteers at the units. RESULTS: A total of 23 units recorded baseline data on 652 people with incident foot ulcers; valid outcome data were available for 541 people (83.0%). Of the 541 index ulcers, 351 (64.9%) healed within 24 weeks, with a median time to healing of 63 days. Ulcer site and depth and peripheral arterial disease were associated with differing ulcer healing rates. By contrast, baseline demographic characteristics were not independently associated with healing. These were used to calculate a standardized case-mix adjusted healing ratio. In most units data collection took < 10 min per person, but participants reported that the burden of local data collection was still excessive. CONCLUSION: This study confirmed the feasibility of routine multi-unit comparative assessment of care of the foot in diabetes, including the generation of meaningful service reports, but for general use the burden of local data collection will need to be reduced (e.g. by using linkage to existing national data collections). PMID- 25131621 TI - Liquid formulation for antibody drugs. AB - Currently many biopharmaceuticals are in use due to their high efficacy and low adverse effects. For antibody drug formulation, liquid ones are being increasingly used. This review focuses on rational liquid antibody formulation development based on the proposed aggregation mechanism of antibody, considering colloidal and conformational stabilities. This review also describes the importance of assessment of physicochemical properties including second virial coefficient of antibody solutions, for the rational and efficient formulation development. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. PMID- 25131619 TI - Fur homolog regulates Porphyromonas gingivalis virulence under low-iron/heme conditions through a complex regulatory network. AB - Porphyromonas gingivalis is a key pathogen responsible for initiation and progression of chronic periodontitis. Little is known about the regulatory mechanisms of iron and heme uptake that allow P. gingivalis to express virulence factors and survive in the hostile environment of the oral cavity, so we initiated characterization of a P. gingivalis Fur homolog (PgFur). Many Fur paralogs found in microbial genomes, including Bacteroidetes, confirm that Fur proteins have a tendency to be subjected to a sub- or even neofunctionalization process. PgFur revealed extremely high sequence divergence, which could be associated with its functional dissimilarity in comparison with other Fur homologs. A fur mutant strain constructed by insertional inactivation exhibited retarded growth during the early growth phase and a significantly lower tendency to form a homotypic biofilm on abiotic surfaces. The mutant also showed significantly weaker adherence and invasion to epithelial cells and macrophages. Transcripts of many differentially regulated genes identified in the fur mutant strain were annotated as hypothetical proteins, suggesting that PgFur can play a novel role in the regulation of gene expression. Inactivation of the fur gene resulted in decreased hmuY gene expression, increased expression of other hmu components and changes in the expression of genes encoding hemagglutinins and proteases (mainly gingipains), HtrA, some extracytoplasmic sigma factors and two component systems. Our data suggest that PgFur can influence in vivo growth and virulence, at least in part by affecting iron/heme acquisition, allowing efficient infection through a complex regulatory network. PMID- 25131622 TI - Clinical whole exome sequencing in child neurology practice. AB - OBJECTIVE: Whole exome sequencing (WES) represents a significant breakthrough in clinical genetics as a powerful tool for etiological discovery in neurodevelopmental disorders. To better characterize the genetic landscape of neurodevelopmental disorders, we analyzed patients in our pediatric neurogenetics clinic who underwent WES. METHODS: We performed a retrospective cohort study on 78 patients with various neurodevelopmental disabilities and unrevealing workup prior to WES. We characterized their molecular diagnoses, clinical features, and whether their previous treatment plan changed due to WES results. RESULTS: The overall presumptive diagnostic rate for our cohort was 41% (n = 32 of 78 patients). Nineteen patients had a single autosomal dominant (AD) disorder, 11 had a single autosomal recessive (AR) disorder, 1 had an X-linked dominant disorder, and 1 had both an AD and an AR disorder. The 32 patients with pathogenic or likely pathogenic variants exhibited various neurobehavioral and neuroimaging abnormalities, including intellectual disability/developmental delay (n = 28), cerebral palsy-like encephalopathy (n = 11), autism spectrum disorder (n = 5), delayed/hypomyelination (n = 7), and cerebellar abnormalities (n = 9). The results of WES affected management for all patients with a presumptive diagnosis, triggering reproductive planning (n = 27), disease monitoring initiation (n = 4), investigation of systemic involvement of the disorder(s) (n = 6), alteration of presumed disease inheritance pattern (n = 7), changing of prognosis (n = 10), medication discontinuation (n = 5) or initiation (n = 2), and clinical trial education (n = 3). INTERPRETATION: The high diagnostic yield of WES supports its use in pediatric neurology practices. It may also lead to earlier diagnosis, impacting medical management, prognostication, and family planning. WES therefore serves as a critical tool for the child neurologist. PMID- 25131624 TI - Stationary wavelet transform for under-sampled MRI reconstruction. AB - In addition to coil sensitivity data (parallel imaging), sparsity constraints are often used as an additional lp-penalty for under-sampled MRI reconstruction (compressed sensing). Penalizing the traditional decimated wavelet transform (DWT) coefficients, however, results in visual pseudo-Gibbs artifacts, some of which are attributed to the lack of translation invariance of the wavelet basis. We show that these artifacts can be greatly reduced by penalizing the translation invariant stationary wavelet transform (SWT) coefficients. This holds with various additional reconstruction constraints, including coil sensitivity profiles and total variation. Additionally, SWT reconstructions result in lower error values and faster convergence compared to DWT. These concepts are illustrated with extensive experiments on in vivo MRI data with particular emphasis on multiple-channel acquisitions. PMID- 25131623 TI - Characterizing pharmacological ligands to study the long-chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4. AB - The free fatty acid receptors (FFA) 1 (previously designated GPR40) and FFA4 (previously GPR120) are two GPCRs activated by saturated and unsaturated longer chain free fatty acids. With expression patterns and functions anticipated to directly or indirectly promote insulin secretion, provide homeostatic control of blood glucose and improve tissue insulin sensitivity, both receptors are being studied as potential therapeutic targets for the control of type 2 diabetes. Furthermore, genetic and systems biology studies in both humans and mouse models link FFA4 receptors to diabetes and obesity. Although activated by the same group of free fatty acids, FFA1 and FFA4 receptors are not closely related and, while the basis of recognition of fatty acids by FFA1 receptors is similar to that of the short-chain fatty acid receptors FFA2 and FFA3, the amino acid residues involved in endogenous ligand recognition by FFA4 receptors are more akin to those of the sphingosine 1 phosphate receptor S1P1 . Screening and subsequent medicinal chemistry programmes have developed a number of FFA1 receptor selective agonists that are effective in promoting insulin secretion in a glucose concentration-dependent manner, and in lowering blood glucose levels. However, the recent termination of Phase III clinical trials employing TAK-875/fasiglifam has caused a setback and raises important questions over the exact nature and mechanistic causes of the problems. Progress in the identification and development of highly FFA4 receptor-selective pharmacological tools has been less rapid and several issues remain to be clarified to fully validate this receptor as a therapeutic target. Despite this, the ongoing development of a range of novel ligands offers great opportunities to further unravel the contributions of these receptors. PMID- 25131625 TI - In vivo quantitative NMR imaging of fruit tissues during growth using Spoiled Gradient Echo sequence. AB - Nondestructive studies of physiological processes in agronomic products require increasingly higher spatial and temporal resolutions. Nuclear Magnetic Resonance (NMR) imaging is a non-invasive technique providing physiological and morphological information on biological tissues. The aim of this study was to design a robust and accurate quantitative measurement method based on NMR imaging combined with contrast agent (CA) for mapping and quantifying water transport in growing cherry tomato fruits. A multiple flip-angle Spoiled Gradient Echo (SGE) imaging sequence was used to evaluate the intrinsic parameters maps M0 and T1 of the fruit tissues. Water transport and paths flow were monitored using Gd(3+)/[Fe(CN)6](3-)/D-mannitol nanoparticles as a tracer. This dynamic study was carried out using a compartmental modeling. The CA was preferentially accumulated in the surrounding tissues of columella and in the seed envelopes. The total quantities and the average volume flow of water estimated are: 198 mg, 1.76 mm(3)/h for the columella and 326 mg, 2.91 mm(3)/h for the seed envelopes. We demonstrate in this paper that the NMR imaging technique coupled with efficient and biocompatible CA in physiological medium has the potential to become a major tool in plant physiology research. PMID- 25131627 TI - Automatic segmentation of white matter lesions on magnetic resonance images of the brain by using an outlier detection strategy. AB - White matter lesions (WMLs) are commonly observed on the magnetic resonance (MR) images of normal elderly in association with vascular risk factors, such as hypertension or stroke. An accurate WML detection provides significant information for disease tracking, therapy evaluation, and normal aging research. In this article, we present an unsupervised WML segmentation method that uses Gaussian mixture model to describe the intensity distribution of the normal brain tissues and detects the WMLs as outliers to the normal brain tissue model based on extreme value theory. The detection of WMLs is performed by comparing the probability distribution function of a one-sided normal distribution and a Gumbel distribution, which is a specific extreme value distribution. The performance of the automatic segmentation is validated on synthetic and clinical MR images with regard to different imaging sequences and lesion loads. Results indicate that the segmentation method has a favorable accuracy competitive with other state-of-the art WML segmentation methods. PMID- 25131626 TI - Decreased oxygen saturation in asymmetrically prominent cortical veins in patients with cerebral ischemic stroke. AB - Decreased oxygen saturation in asymmetrically prominent cortical veins (APCV) seen in ischemic stroke has been hypothesized to correlate with an increase of de oxygenated hemoglobin. Our goal is to quantify magnetic susceptibility to define APCV by establishing a cutoff above which the deoxyhemoglobin levels are considered abnormal. A retrospective study was conducted on 26 patients with acute ischemic stroke in one cerebral hemisphere that exhibited APCV with 30 age- and sex-matched healthy controls. Quantitative susceptibility mapping (QSM) was used to calculate the magnetic susceptibility of the cortical veins. A paired t test was used to compare the susceptibility of the cortical veins in the left and right hemispheres for healthy controls as well as in the contralateral hemisphere for stroke patients with APCV. The change in oxygen saturation in the APCV relative to the contralateral side was calculated after thresholding the susceptibility using the mean plus two standard deviations of the contralateral side for each individual. The thresholded susceptibility value of the APCVs in the stroke hemisphere was 254+/-48 ppb which was significantly higher (p<0.05) than that in the contralateral hemisphere (123+/-12 ppb) and in healthy controls (125+/-8 ppb). There was a decrease of oxygen saturation in the APCV ranging from 16% to 44% relative to the veins of the contralateral hemisphere. In conclusion, APCV seen in SWI correspond to reduced levels of oxygen saturation and these abnormal veins can be identified using a susceptibility threshold on the QSM data. PMID- 25131628 TI - Intravoxel incoherent motion diffusion-weighted imaging in head and neck squamous cell carcinoma: assessment of perfusion-related parameters compared to dynamic contrast-enhanced MRI. AB - PURPOSE: To investigate the correlation between perfusion-related parameters obtained with intravoxel incoherent motion (IVIM) and classical perfusion parameters obtained with dynamic contrast-enhanced (DCE) magnetic resonance imaging in patients with head and neck squamous cell carcinoma (HNSCC), and to compare direct and asymptotic fitting, the pixel-by-pixel approach, and a region of interest (ROI)-based approach respectively for IVIM parameter calculation. MATERIALS AND METHODS: Seventeen patients with HNSCC were included in this retrospective study. All magnetic resonance (MR) scanning was performed using a 3T MR unit. Acquisition of IVIM was performed using single-shot spin-echo echo planar imaging with three orthogonal gradients with 12 b-values (0, 10, 20, 30, 50, 80, 100, 200, 400, 800, 1000, and 2000). Perfusion-related parameters of perfusion fraction 'f' and the pseudo-diffusion coefficient 'D*' were calculated from IVIM data by using least square fitting with the two fitting methods of direct and asymptotic fitting, respectively. DCE perfusion was performed in a total of 64 dynamic phases with a 3.2-s phase interval. The two-compartment exchange model was used for the quantification of tumor blood volume (TBV) and tumor blood flow (TBF). Each tumor was delineated with a polygonal ROI for the calculation of f, f?D* performed using both the pixel-by-pixel approach and the ROI-based approach. In the pixel-by-pixel approach, after fitting each pixel to obtain f, f?D* maps, the mean value in the delineated ROI on these maps was calculated. In the ROI-based approach, the mean value of signal intensity was calculated within the ROI for each b-value in IVIM images, and then fitting was performed using these values. Correlations between f in a total of four combinations (direct or asymptotic fitting and pixel-by-pixel or ROI-based approach) and TBV were respectively analyzed using Pearson's correlation coefficients. Correlations between f?D* and TBF were also similarly analyzed. RESULTS: In all combinations of f and TBV, f?D* and TBF, there was a significant correlation. In the comparison of f and TBV, a moderate correlation was observed only between f obtained by direct fitting with the pixel-by-pixel approach, whereas a good correlation was observed in the comparisons using the other three combinations. In the comparison of f?D* and TBF, a good correlation was observed only with f?D* obtained by asymptotic fitting with the ROI-based approach. In contrast, moderate correlations were observed in the comparisons using the other three combinations. CONCLUSION: IVIM was found to be feasible for the analysis of perfusion-related parameters in patients with HNSCC. Especially, the combination of asymptotic fitting with the ROI-based approach was better correlated with DCE perfusion. PMID- 25131630 TI - Aligning 3D time-of-flight MRA datasets for quantitative longitudinal studies: evaluation of rigid registration techniques. AB - OBJECTIVE: 3D Time-of-flight (TOF) magnetic resonance angiography is commonly used for vascular analyses. A quantification of longitudinal morphological changes usually requires the registration of TOF image sequences acquired at different time points. The aim of this study was to evaluate the precision of different 3D rigid registration setups such that an optimal quantification of morphological changes can be achieved. METHODS: Eight different rigid registration techniques were implemented and evaluated in this study using the target registration error (TRE) calculated based on 554 landmarks defined in twenty TOF datasets. The registration techniques differed in integration of brain and vessel segmentation masks and usage of a multi-resolution framework. Furthermore, the benefit of a prior volume-of-interest definition for registration accuracy was evaluated. RESULTS: The results revealed that the highest registration accuracies can be achieved using a multi-resolution framework and a cerebrovascular segmentation as mask. Numerically, a mean TRE of 1.1mm was calculated. If applicable, a prior definition of a volume-of-interest allows a reduction of the TRE to only 0.6mm. CONCLUSION: TOF datasets should be registered using vessel segmentations as mask, multi-resolution framework and previous volume-of-interest definition if possible to obtain the highest registration precision. This is especially the case for longitudinal datasets that are separated by several months while the registration technique seems less important for datasets that are only separated by a few days. PMID- 25131629 TI - Delayed gadolinium-enhanced MRI of the fibrocartilage disc of the temporomandibular joint--a feasibility study. AB - OBJECTIVE: To 1) test the feasibility of delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) at 3 T in the temporomandibular joint (TMJ) and 2) to determine the optimal delay for measurements of the TMJ disc after i.v. contrast agent (CA) administration. DESIGN: MRI of the right and left TMJ of six asymptomatic volunteers was performed at 3 T using a dedicated coil. 2D inversion recovery (2D-IR) sequences were performed at 4 time points covering 120 minutes and 3D gradient-echo (3D GRE) dual flip-angle sequences were performed at 14 time points covering 130 minutes after the administration of 0.2 mmol/kg of Gd-diethylenetriamine pentaacetic acid ion (Gd-DTPA)(2-), i.e., 0.4 mL of MagnevistTM per kg body weight. Pair-wise tests were used to assess differences between pre-and post-contrast T1 values. RESULTS: 2D-IR sequences showed a statistically significant drop (p<0.001) in T1 values after i.v. CA administration. The T1 drop of 50% was reached 60 minutes after bolus injection in the TMJ disc. The 3D GRE dual flip-angle sequences confirmed these results and show plateau of T1 after 60 minutes. CONCLUSIONS: T1(Gd) maps calculated from dGEMRIC data allow in vivo assessment of the fibrocartilage disc of the TMJ. The recommended measurement time for dGEMRIC in the TMJ after i.v. CA administration is from 60 to 120 minutes. PMID- 25131631 TI - Image registration guided, sparsity constrained reconstructions for dynamic MRI. AB - It is generally a challenging task to reconstruct dynamic magnetic resonance (MR) images with high spatial and high temporal resolutions, especially with highly incomplete k-space sampling. In this work, a novel method that combines a non rigid image registration technique with sparsity-constrained image reconstruction is introduced. Employing a multi-resolution free-form deformation technique with B-spline interpolations, the non-rigid image registration accurately models the complex deformations of the physiological dynamics, and provides artifact suppressed high spatial-resolution predictions. Based on these prediction images, the sparsity-constrained data fidelity-enforced image reconstruction further improves the reconstruction accuracy. When compared with the k-t FOCUSS with motion estimation/motion compensation (MEMC) technique on volunteer scans, the proposed method consistently outperforms in both the spatial and the temporal accuracy with variously accelerated k-space sampling. High fidelity reconstructions for dynamic systolic phases with reduction factor of 10 and cardiac perfusion series with reduction factor of 3 are presented. PMID- 25131632 TI - Synthesis of tetraphenylethylene pillar[6]arenes and the selective fast quenching of their AIE fluorescence by TNT. AB - Tetraphenylethylene pillar[6]arenes with an AIE effect were synthesized for the first time. The fluorescence of the pillar[6]arenes could be quenched much more and much faster by TNT than by other nitroaromatics including 2,4,6 trinitrophenol, which could be used to detect TNT in air. PMID- 25131633 TI - Design of a Gd-DOTA-phthalocyanine conjugate combining MRI contrast imaging and photosensitization properties as a potential molecular theranostic. AB - The design and synthesis of a phthalocyanine--Gd-DOTA conjugate is presented to open the way to novel molecular theranostics, combining the properties of MRI contrast imaging with photodynamic therapy. The rational design of the conjugate integrates isomeric purity of the phthalocyanine core substitution, suitable biocompatibility with the use of polyoxo water-solubilizing substituents, and a convergent synthetic strategy ended by the use of click chemistry to graft the Gd DOTA moiety to the phthalocyanine. Photophysical and photochemical properties, contrast imaging experiments and preliminary in vitro investigations proved that such a combination is relevant and lead to a new type of potential theranostic agent. PMID- 25131635 TI - Text Mining Driven Drug-Drug Interaction Detection. AB - Identifying drug-drug interactions is an important and challenging problem in computational biology and healthcare research. There are accurate, structured but limited domain knowledge and noisy, unstructured but abundant textual information available for building predictive models. The difficulty lies in mining the true patterns embedded in text data and developing efficient and effective ways to combine heterogenous types of information. We demonstrate a novel approach of leveraging augmented text-mining features to build a logistic regression model with improved prediction performance (in terms of discrimination and calibration). Our model based on synthesized features significantly outperforms the model trained with only structured features (AUC: 96% vs. 91%, Sensitivity: 90% vs. 82% and Specificity: 88% vs. 81%). Along with the quantitative results, we also show learned "latent topics", an intermediary result of our text mining module, and discuss their implications. PMID- 25131636 TI - Electrical conduction behavior of organic light-emitting diodes using fluorinated self-assembled monolayer with molybdenum oxide-doped hole transporting layer. AB - The electrical conductivity behavior of a fluorinated self-assembled monolayer (FSAM) of a molybdenum oxide (MoOx)-doped alpha-naphthyl diamine derivative (alpha-NPD) in organic light-emitting diodes (OLEDs) was investigated. The current density of the MoOx-doped alpha-NPD/FSAM device was proportional to its voltage owing to smooth carrier injection through the FSAM and the high carrier density of its bulk. The temperature-dependent characteristics of this device were investigated. The current density-voltage characteristics at different temperatures were almost the same owing to its very low activation energy. The activation energy of the device was estimated to be 1.056 * 10(-2) [eV] and was very low due to the inelastic electron tunneling of FSAM molecules. PMID- 25131634 TI - Expression profile analysis of vulnerable CA1 pyramidal neurons in young-Middle Aged Ts65Dn mice. AB - Down syndrome (DS) is the most prevalent cause of intellectual disability (ID). Individuals with DS show a variety of cognitive deficits, most notably in hippocampal learning and memory, and display pathological hallmarks of Alzheimer's disease (AD), with neurodegeneration of cholinergic basal forebrain (CBF) neurons. Elucidation of the molecular and cellular underpinnings of neuropathology has been assessed via gene expression analysis in a relevant animal model, termed the Ts65Dn mouse. The Ts65Dn mouse is a segmental trisomy model of DS that mimics DS/AD pathology, notably age-related cognitive dysfunction and degeneration of basal forebrain cholinergic neurons (BFCNs). To determine expression level changes, molecular fingerprinting of cornu ammonis 1 (CA1) pyramidal neurons was performed in adult (4-9 month-old) Ts65Dn mice, at the initiation of BFCN degeneration. To quantitate transcriptomic changes during this early time period, laser capture microdissection (LCM), terminal continuation (TC) RNA amplification, custom-designed microarray analysis, and subsequent validation of individual transcripts by qPCR and protein analysis via immunoblotting was performed. The results indicate significant alterations within CA1 pyramidal neurons of Ts65Dn mice compared with normal disomic (2N) littermates, notably in the downregulation of neurotrophins and their cognate neurotrophin receptors among other classes of transcripts relevant to neurodegeneration. The results of this single-population gene expression analysis at the time of septohippocampal deficits in a trisomic mouse model shed light on a vulnerable circuit that may cause the AD-like pathology invariably seen in DS that could help to identify mechanisms of degeneration, and provide novel gene targets for therapeutic interventions. J. Comp. Neurol. 523:61-74, 2015. (c) 2014 Wiley Periodicals, Inc. PMID- 25131637 TI - Setting the stage for development of a program for adolescent heart transplant recipients to transition to adult providers: An integrative review of the literature. AB - PURPOSE: This integrative review of the literature was undertaken to determine if there was a body of knowledge to support a transition program in an adolescent heart transplant population. CONCLUSIONS: No studies were found involving a heart transplant transition program for adolescents. A literature review for transition in other chronic illness areas was undertaken. Youth with chronic illness are inadequately prepared to transfer to adult providers. Transition programs should be developed. These programs should be tailored to suit individual needs. They should teach disease knowledge and encourage participation in self-management skills. Participation in a transition program improved patients' quality of life and improved their knowledge about their disease. PRACTICE IMPLICATIONS: Nurses are in a unique position with chronically ill adolescents to promote positive behaviors at every interaction. Encouraging self-management behaviors will support these youth as they prepare to become adults. PMID- 25131638 TI - Gorlin syndrome (nevoid basal cell carcinoma syndrome): update and literature review. AB - Gorlin syndrome, also called nevoid basal cell carcinoma syndrome, is an autosomal dominant neurocutaneous disease characterized by developmental anomalies such as palmar pits and rib anomaly, and tumorigenesis such as medulloblastoma and basal cell carcinoma. This syndrome is mainly caused by a mutation of PTCH1, a human homologue of Drosophila patched, including frameshift, missense, or nonsense mutations. Genotype-phenotype correlation has not been established. PTCH1 is a member of hedgehog signaling, which is a highly conserved pathway in vertebrates, composed of hedgehog, SMO, and GLI proteins as well as PTCH1. Given that hedgehog signaling regulates cell growth and development, disorder of this pathway gives rise to not only developmental anomalies but also diverse tumors such as those seen in Gorlin syndrome. We recently reported, for the first time, a nationwide survey of Gorlin syndrome in Japan, noting that the frequency was 1/235,800 in the Japanese population, and that the frequency of basal cell carcinomas was significantly lower in Japan than in the USA and Europe, suggesting that ethnicity and genetic background contribute to these differences. Given that many clinical trials using newly discovered molecular inhibitors are still ongoing, these agents should become the new therapeutic options for hedgehog pathway-dependent tumors in patients with or without Gorlin syndrome. PMID- 25131639 TI - Dark macules in the upper gastrointestinal tract: an ominous sign. PMID- 25131641 TI - 'Not-so-minor' stroke: Lasting psychosocial consequences of anterior cingulate cortical ischemia in the rat. AB - Patients with small, non-debilitating strokes often report a reduction in quality of life due to persistent cognitive and emotional alterations. Stroke may directly damage limbic circuitry resulting in an impaired stress response, however the possibility that this may in part explain the prevalence of stroke comorbidity with mood disorders has yet to be determined. Here we systematically examine psychosocial consequences of prefrontal lesions targeting the left anterior cingulate cortex (ACC) using hormone assays and a behavioral test battery in adult rats to probe whether a small stroke could alter stress behavior or response to psychosocial stress (chronic mild stress (CMS) or subordination stress). Minor stroke produced chronic hyperactivity in an open field but did not alter fear-related inhibition in the elevated plus maze. Novelty-induced defecation was increased by the combination of CMS, subordination and stroke. Anterior cingulate lesions alone increased distress vocalizations in the water maze. Interestingly, ACC stroke caused hyper-secretion of porphyrin and long-term hormonal alterations that resulted in adrenal hypertrophy and enhanced dexamethasone suppression of the HPA axis. We propose that this behavioral profile is consistent with an animal model of post-stroke distress-like syndrome which could be useful in understanding how stroke affects the capacity to cope with psychological stress. PMID- 25131642 TI - International Classification of Functioning, Disability and Health Core Sets for children and youth with cerebral palsy: a consensus meeting. AB - AIM: The objective of this article is to report on the Core Sets developed for children and youth aged 0 to 18 years, with cerebral palsy (CP) based on the pediatric International Classification of Functioning, Disability and Health (ICF) by the World Health Organization (WHO). METHOD: A formal decision-making and consensus process integrating evidence gathered from preparatory studies was followed. Preparatory studies included: a systematic literature review; an international expert survey; a qualitative study of children and youth with CP and their caregivers; and a clinical study. Relevant ICF categories were identified in a formal consensus process by international experts from different backgrounds. Twenty-six international experts chosen by WHO region with expertise in CP attended the consensus meeting. RESULTS: Overall, five ICF Core Sets were developed: a Comprehensive Core Set (135 ICF categories); a Common Brief (25 ICF categories); and three age-specific Core Sets: under 6 years (31 ICF categories), from 6 to <14 years (35 ICF categories) and from 14 to 18 years (37 ICF categories). INTERPRETATION: These ICF Core Sets for children and youth with CP are the first ICF-based tools developed for this population. The ICF Core Sets for children and youth with CP can be applied in clinical practice, research, teaching and administration. The application of the ICF Core Sets to this population will standardize the functional assessments of CP worldwide. PMID- 25131640 TI - Epigenetics and sex differences in the brain: A genome-wide comparison of histone 3 lysine-4 trimethylation (H3K4me3) in male and female mice. AB - Many neurological and psychiatric disorders exhibit gender disparities, and sex differences in the brain likely explain some of these effects. Recent work in rodents points to a role for epigenetics in the development or maintenance of neural sex differences, although genome-wide studies have so far been lacking. Here we review the existing literature on epigenetics and brain sexual differentiation and present preliminary analyses on the genome-wide distribution of histone-3 lysine-4 trimethylation in a sexually dimorphic brain region in male and female mice. H3K4me3 is a histone mark primarily organized as 'peaks' surrounding the transcription start site of active genes. We microdissected the bed nucleus of the stria terminalis and preoptic area (BNST/POA) in adult male and female mice and used ChIP-Seq to compare the distribution of H3K4me3 throughout the genome. We found 248 genes and loci with a significant sex difference in H3K4me3. Of these, the majority (71%) had larger H3K4me3 peaks in females. Comparisons with existing databases indicate that genes and loci with increased H3K4me3 in females are associated with synaptic function and with expression atlases from related brain areas. Based on RT-PCR, only a minority of genes with a sex difference in H3K4me3 has detectable sex differences in expression at baseline conditions. Together with previous findings, our data suggest that there may be sex biases in the use of epigenetic marks. Such biases could underlie sex differences in vulnerabilities to drugs or diseases that disrupt specific epigenetic processes. PMID- 25131643 TI - Systematic review of epilepsy self-management interventions integrated with a synthesis of children and young people's views and experiences. AB - AIM: To determine the effectiveness of epilepsy self-management interventions and explore the views and experiences of medication and seizures by children and young people. BACKGROUND: Experiencing seizures and side-effects from anti epileptic medicines have negative impacts on children and young people managing their epilepsy. Children commonly experiment with not taking epilepsy medication as prescribed and engage in unhealthy lifestyles. DESIGN/REVIEW METHODS: Mixed method systematic review with theory development. Cochrane quantitative methods and thematic synthesis of qualitative and survey evidence. DATA SOURCES: Eight databases were searched from earliest dates to July 2013. RESULTS: Nineteen studies were included. Meta-analysis was not possible. Zero of nine intervention studies showed improvement in anti-epilepsy medication adherence. Skill-based behavioural techniques with activities such as role play and goal setting with young people increased epilepsy knowledge and seizure self-management (small effects). Intervention studies were methodologically weak and no studies reported if improvement in self-management was sustained over time. Synthesis of nine qualitative and one mixed-method studies generated six themes encapsulating anti epilepsy medication and epilepsy effects. There was a lack of fidelity between intervention programme theories and what children and young people found difficult with medication self-management and managing the effects of epilepsy. CONCLUSION: Children and young people knowingly and/or unknowingly take risks with their epilepsy and give reasoned explanations for doing so. There are no effective interventions to change epilepsy medication adherence behaviours. There is an urgent need for more innovative and individually tailored interventions to address specific challenges to epilepsy self-management as identified by children and young people themselves. PMID- 25131644 TI - Surgical repositioning of a developing maxillary central incisor. A case report. AB - BACKGROUND: A traumatic injury to the primary dentition can cause damage to the germ of the permanent successor. As a clinical consequence a dilaceration with root deformation, malpositioning and disturbances of eruption can occur. Surgical repositioning of such a dislocated crown of a developing tooth can be a treatment option. CASE REPORT: A four year old patient was referred to our clinic because of a mobile upper primary central incisor and a radiographically visible displaced dental crown. Her history revealed a traumatic dental injury one year ago. Radiologic examination confirmed an inflammatory root resorption on tooth 61 and a dislocation of the developing tooth 21. In order to avoid further displacement due to the inflammation, 61 was extracted at the first appointment. A radiographic image 7 months later showed no improvement in the malposition of tooth 21. Therefore tooth 21 was surgically repositioned into its correct position. Follow-up over 3 years confirmed a continued root development and a full eruption of 21 in its correct position. CONCLUSION: Early diagnosis and early treatment of a dislocated permanent tooth germ is essential to allow a favorable outcome. Surgical repositioning can be successful in avoiding later malpositioning of the permanent teeth. PMID- 25131645 TI - Declining trends in the proportion of non-viral sexually transmissible infections reported by STD clinics in the US, 2000-10. AB - Background Recent budget shortfalls may have resulted in decreases in the number of sexually transmissible infections (STIs) reported from sexually transmitted disease clinics (STDCs) in the United States (US). The objective of this study was to examine the proportion of cases reported from STDCs for three non-viral STIs in the last decade. METHODS: Data from the national surveillance database on primary and secondary (P&S) syphilis, gonorrhoea and chlamydia cases for 2000-10 were extracted. The percentage of cases reported by STDCs for the nation and for each of the 48 contiguous states were then computed. Finally, the chi(2) trend test for proportions was used to determine the annual average decrease/increase in the percentage of cases reported by STDCs for the nation and for each state. RESULTS: RESULTS demonstrate that the average annual declines in the proportion of P&S syphilis, gonorrhoea, and chlamydia cases reported from STDCs were 1.43% (P<0.01), 1.31% (P<0.01), and 0.31% (P<0.01), respectively. Additionally, most of the states with statistically significant trends (P<0.05) in the proportion of cases reported by STDCs had negative slopes: 86% (25/29) for P&S syphilis, 89% (34/38) for gonorrhoea, and 63% (27/43) for chlamydia. CONCLUSION: These results document the declining role of STDCs in STI prevention and control efforts in the US. Further studies are needed to assess the direct or indirect impact of the decline in the proportion of cases from STDCs on the overall STI control and prevention efforts in the US and its implications for the future. PMID- 25131646 TI - Enzymatic routes for the synthesis of ursodeoxycholic acid. AB - Ursodeoxycholic acid, a secondary bile acid, is used as a drug for the treatment of various liver diseases, the optimal dose comprises the range of 8-10mg/kg/day. For industrial syntheses, the structural complexity of this bile acid requires the use of an appropriate starting material as well as the application of regio- and enantio-selective enzymes for its derivatization. Most strategies for the synthesis start from cholic acid or chenodeoxycholic acid. The latter requires the conversion of the hydroxyl group at C-7 from alpha- into beta-position in order to obtain ursodeoxycholic acid. Cholic acid on the other hand does not only require the same epimerization reaction at C-7 but the removal of the hydroxyl group at C-12 as well. There are several bacterial regio- and enantio-selective hydroxysteroid dehydrogenases (HSDHs) to carry out the desired reactions, for example 7alpha-HSDHs from strains of Clostridium, Bacteroides or Xanthomonas, 7beta-HSDHs from Clostridium, Collinsella, or Ruminococcus, or 12alpha-HSDH from Clostridium or from Eggerthella. However, all these bioconversion reactions need additional steps for the regeneration of the coenzymes. Selected multi-step reaction systems for the synthesis of ursodeoxycholic acid are presented in this review. PMID- 25131647 TI - Hepatitis C virus: the 25-year journey from discovery to cure. PMID- 25131648 TI - Identity, causality, and pronoun ambiguity. AB - This article looks at the way people determine the antecedent of a pronoun in sentence pairs, such as: Albert invited Ron to dinner. He spent hours cleaning the house. The experiment reported here is motivated by the idea that such judgments depend on reasoning about identity (e.g., the identity of the he who cleaned the house). Because the identity of an individual over time depends on the causal-historical path connecting the stages of the individual, the correct antecedent will also depend on causal connections. The experiment varied how likely it is that the event of the first sentence (e.g., the invitation) would cause the event of the second (the house cleaning) for each of the two individuals (the likelihood that if Albert invited Ron to dinner, this would cause Albert to clean the house, versus cause Ron to clean the house). Decisions about the antecedent followed causal likelihood. A mathematical model of causal identity accounted for most of the key aspects of the data from the individual sentence pairs. PMID- 25131649 TI - Variation of system performance, quality control standards and adherence to international FDG-PET/CT imaging guidelines. A national survey of PET/CT operations in Austria. AB - AIM: To gather information on clinical operations, quality control (QC) standards and adoption of guidelines for FDG-PET/CT imaging in Austrian PET/CT centres. METHODS: A written survey composed of 68 questions related to A) PET/CT centre and installation, B) standard protocol parameters for FDG-PET/CT imaging of oncology patients, and C) standard QC procedures was conducted between November and December 2013 among all Austrian PET/CT centres. In addition, a NEMA-NU2 2012 image quality phantom test was performed using standard whole-body imaging settings on all PET/CT systems with a lesion-to-background ratio of 4. Recovery coefficients (RC) were calculated for each lesion and PET/CT system. RESULTS: A) 13 PET/CT systems were installed in 12 nuclear medicine departments at public hospitals. B) Average fasting prior to FDG-PET/CT was 7.6 (4-12) h. All sites measured blood glucose levels while using different cut-off levels (64%: 150 mg/dl). Weight-based activity injection was performed at 83% sites with a mean FDG activity of 4.1 MBq/kg. Average FDG uptake time was 55 (45-75) min. All sites employed CT contrast agents (variation from 1%-95% of the patients). All sites reported SUV-max. C) Frequency of QC tests varied significantly and QC phantom measurements revealed significant differences in RCs. CONCLUSION: Significant variations in FDG-PET/CT protocol parameters among all Austrian PET/CT users were observed. Subsequently, efforts need to be put in place to further standardize imaging protocols. At a minimum clinical PET/CT operations should ensure compliance with existing guidelines. Further, standardized QC procedures must be followed to improve quantitative accuracy across PET/CT centres. PMID- 25131650 TI - Weight maintenance from young adult weight predicts better health outcomes. AB - OBJECTIVE: Defining groups of individuals within a larger population with similar patterns of weight change over time may provide insight into influences of weight stability or gain. METHODS: Latent class growth modeling was used to define subgroups of weight change in adult members of the Gila River Indian Community participating in at least four non-diabetic health exams including OGTTs (N = 1,157, 762F/395M; 78.4 +/- 19.0 kg). In a separate study, 152 individuals had 24 h EE measured in a respiratory chamber. RESULTS: Eight groups with baseline weights of 54.6 +/- 7.3 (n = 124), 64.2 +/- 7.7 (n = 267), 73.6 +/- 7.8 (n = 298), 86.1 +/- 10.2 (n = 194), 95.5 +/- 6.7 (n = 90), 97.9 +/- 10.4 (n = 92), 110.9 +/- 11.9 (n = 61), and 122.1 +/- 13.6 (n = 31) kg (P < 0.001) were delineated. Group 5, (initial weight = 95.5 +/- 6.7 kg) maintained a comparatively stable weight over time (+3.3 +/- 10.3 kg, +3.8 +/- 11.2% of initial weight; median follow-up time: 13.1 years). All other groups gained weight over time (+29.9 +/- 21.1% of initial weight; median follow-up time: 16.3 years). Higher starting weight defined weight gain in most groups, but higher 2 h glucose predicted membership in the lower weight trajectories. The weight stable group had higher rates of impaired glucose regulation at baseline and higher 24-h EE. CONCLUSIONS: Weight in young adulthood defined weight gain trajectory underscoring the importance of intervening early to prevent weight gain. PMID- 25131651 TI - Fungal diversity, incidence and mycotoxin contamination in grapes from two agro climatic Spanish regions with emphasis on Aspergillus species. AB - BACKGROUND: Fourteen vineyards from two different agro-climatic regions in Spain were sampled in two consecutive years in order to determinate the grape mycobiota and diversity indexes with the final aim to define the potential mycotoxigenic species from both regions and their relationship. RESULTS: The most common fungal genera encountered were Aspergillus (30.0%), Alternaria (53.2%), Cladosporium (11.9%) and Penicillium (2.9%). Black aspergilli presence in the hotter region (south) was significantly higher (P < 0.05) than in the northeast in both years. Among black aspergilli, A. tubingensis seemed to be the better adapted species to environmental conditions, while A. carbonarius was the main potentially ochratoxigenic species in both regions and years, owing to the most relevant percentage of ochratoxigenic isolates. Ochratoxin A (OTA)-positive musts were only detected from southern vineyards, although contamination was always lower than 0.1 ug L(-1) . Finally, none of black aspergilli tested produced fumonisins (FBs) on Czapek yeast extract agar (CYA), while 63% of A. niger tested produced FB2 when inoculated on CYA20S, reaching 100% of isolates from the south. CONCLUSION: Climate change scenarios in southern Europe point to an increase in temperature and drought. This could promote particularly adapted species such as A. niger, decreasing OTA risk, but this could lead to an increase in FB2 presence. PMID- 25131652 TI - Free-breathing multislice native myocardial T1 mapping using the slice interleaved T1 (STONE) sequence. AB - PURPOSE: To develop a novel pulse sequence for free-breathing, multislice, native myocardial T1 mapping. METHODS: The slice-interleaved T1 (STONE) sequence consists of multiple sets of single-shot images of different slices, acquired after a single nonselective inversion pulse. Each slice is only selectively excited once after each inversion pulse to allow sampling of the unperturbed longitudinal magnetization in the adjacent slices. For respiratory motion, a prospective slice-tracking respiratory navigator is used to decrease through plane motion followed by a retrospective image registration to reduce in-plane motion. STONE T1 maps were calculated using both a two-parameter and three parameter fit model. The accuracy and precision of the STONE sequence for different T1 , T2 , and inversion pulse efficiency were studied using numerical simulations and phantom experiments. T1 maps from 14 subjects were acquired with the STONE sequence and T1 s were compared to the MOdified Look-Locker Inversion recovery sequence (MOLLI). RESULTS: In numerical simulations and phantom experiments, the STONE sequence using a two-parameter fit model yields more accurate T1 times compared to MOLLI, with similar high precision. The three parameter fit model further improves the accuracy, but with a reduced precision. The native myocardial T1 times were higher in the STONE sequence using two- or three-parameter fit compared to MOLLI. The standard deviation of the T1 times was lower in the STONE T1 maps with a two-parameter fit compared with MOLLI or a three-parameter fit. CONCLUSION: The STONE sequence allows accurate and precise quantification of native myocardial T1 times with the additional benefit of covering the entire ventricle. Magn Reson Med 74:115-124, 2015. (c) 2014 Wiley Periodicals, Inc. PMID- 25131653 TI - Investigating the role of social-affective attachment processes in cradling bias: the absence of cradling bias in children with Autism Spectrum Disorders. AB - Previous studies suggest that leftward cradling bias may facilitate mother-infant relationships, as it preferentially locates the infant in the mother's left hemi space, which is specialized for several social-affective processes. If leftward cradling bias is mediated by social-affective attachment processes, it should be reduced in humans who are deficient in such processes. Individuals diagnosed with Autism Spectrum Disorders (ASDs) constitute a population with known deficits in social and emotional relating. A pilot study confirmed reduced bias in this group, and in the present study, we elaborated methods to assess also the impact of higher cognitive processes on cradling bias. Direct systematic observation was used to investigate the occurrence of cradling bias in ASD, non-ASD intellectually disabled children and typically developing children. Ninety-three participants aged 5-15 years cradled a life-like doll on four separate occasions. Intelligence and executive functions were assessed. Regression analyses revealed that ASD diagnosis was the only significant predictor of atypical cradling preference. While intellectually disabled and typically developing children clearly preferred to cradle to the left, no preference was evident in the ASD group. Results support the hypothesis that leftward cradling bias is associated with basic social-affective capacities. PMID- 25131654 TI - Bortezomib for effective treatment of a child with refractory autoimmune hemolytic anemia post allogeneic hematopoietic stem cell transplant. PMID- 25131655 TI - Membrane pathology and microglial activation of mice expressing membrane anchored or membrane released forms of Abeta and mutated human Alzheimer's precursor protein (APP). AB - AIMS: Alzheimer's disease and the transmissible spongiform encephalopathies or prion diseases accumulate misfolded and aggregated forms of neuronal cell membrane proteins. Distinctive membrane lesions caused by the accumulation of disease-associated prion protein (PrP(d)) are found in prion disease but morphological changes of membranes are not associated with Abeta in Alzheimer's disease. Membrane changes occur in all prion diseases where PrP(d) is attached to cell membranes by a glycosyl-phosphoinositol (GPI) anchor but are absent from transgenic mice expressing anchorless PrP(d). Here we investigate whether GPI membrane attached Abeta may also cause prion-like membrane lesions. METHODS: We used immunogold electron microscopy to determine the localization and pathology of Abeta accumulation in groups of transgenic mice expressing anchored or unanchored forms of Abeta or mutated human Alzheimer's precursor protein. RESULTS: GPI attached Abeta did not replicate the membrane lesions of PrP(d). However, as with PrP(d) in prion disease, Abeta peptides derived from each transgenic mouse line initially accumulated on morphologically normal neurite membranes, elicited rapid glial recognition and neurite Abeta was transferred to attenuated microglial and astrocytic processes. CONCLUSIONS: GPI attachment of misfolded membrane proteins is insufficient to cause prion-like membrane lesions. Prion disease and murine Abeta amyloidosis both accumulate misfolded monomeric or oligomeric membrane proteins that are recognized by glial processes and acquire such misfolded proteins prior to their accumulation in the extracellular space. In contrast to prion disease where glial cells efficiently endocytose PrP(d) to endolysosomes, activated microglial cells in murine Abeta amyloidosis are not as efficient phagocytes. PMID- 25131657 TI - Non-statistical key issues in conducting sensible observational studies to resolve clinical questions. PMID- 25131656 TI - DNA methylation aberrations rather than polymorphisms of FZD3 gene increase the risk of spina bifida in a high-risk region for neural tube defects. AB - BACKGROUND: Animal models of neural tube defects (NTDs) have indicated roles for the Fzd3 gene and the planar cell polarity signaling pathway in convergent extension. We investigated the involvement of FZD3 in genetic and epigenetic mechanisms associated with human NTDs, especially spina bifida. We explored the effects of variants spanning the FZD3 gene in NTDs and examined the role of aberrant methylation of the FZD3 promoter on gene expression in brain tissue in spina bifida. METHODS: Six FZD3 single nucleotide polymorphisms were genotyped using a MassARRAY system in tissue from 165 NTD fetuses and 152 controls. DNA methylation aberrations in the FZD3 promoter region were detected using a MassARRAY EpiTYPER (17 CpG units from -500 to -2400 bp from the transcription start site) in brain tissue from 77 spina bifida and 74 control fetuses. RESULTS: None of the six single nucleotide polymorphisms evaluated were significantly associated with spina bifida, but the mean methylation level was significantly higher in spina bifida samples (13.70%) compared with control samples (10.91%) (p = 0.001). In terms of specific sites, DNA methylation levels were significantly higher in the spina bifida samples at 14 of the 17 CpG units, which mostly included in R2 region. FZD3 mRNA expression was negatively correlated with methylation of the FZD3 promoter region, especially the R2 region (R = 0.970; p = 0.001) in HeLa cells. CONCLUSION: The results of this study suggest that DNA methylation plays an important role in FZD3 gene expression regulation and may be associated with an increased risk of spina bifida. PMID- 25131658 TI - Factors associated with receiving treatment for dental decay among Medicaid enrolled children younger than 12 years of age in Iowa, 2010. AB - OBJECTIVES: The Iowa Department of Public Health I-Smile program provides dental screening and care coordination to over 23,000 low-income and Medicaid-enrolled children per year. The purposes of this study were to evaluate I-Smile program effectiveness to ensure that Medicaid-enrolled children obtained dental treatment after having been screened and to determine the factors associated with failure to receive dental care after screening through the I-Smile program. METHODS: Based on I-Smile program priorities, we limited our sample to children younger than 12 years of age who screened positive for decay and who linked to a paid Medicaid claim for dental treatment (n = 1,816). We conducted bivariate analyses to examine associations between children's characteristics who screened positive for decay and received treatment within 6 months of their initial screening. We also performed multivariate logistic regression to assess the association of sociodemographic characteristics with receipt of treatment among children who screened positive for decay. RESULTS: Eleven percent of children screened positive for decay. Nearly 24 percent of children with decay received treatment based on a Medicaid-paid claim. Being 5 years or older [adjusted odds ratio (aOR): 1.48, confidence interval (CI): 1.17, 1.88] and not having a dental home (aOR: 1.90, CI: 1.41, 2.58) were associated with higher odds of not receiving dental treatment. CONCLUSIONS: Children 5 years and older and without a dental home were less likely to obtain dental treatment. Opportunities exist for the I Smile program to increase the numbers of at-risk children with dental homes and who obtain dental care after screening. PMID- 25131659 TI - MALDI imaging-based identification of prognostically relevant signals in bladder cancer using large-scale tissue microarrays. AB - OBJECTIVE: Although most patients with urinary bladder cancer present with noninvasive and low-malignant stages of the disease, about 20% eventually develop life-threatening metastatic tumors. This study was designed to evaluate the potential of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify molecular markers predicting the clinical course of bladder cancer. MATERIALS AND METHODS: We employed MALDI-MSI to a bladder cancer tissue microarray including paraffin-embedded tissue samples from 697 patients with clinical follow-up data to search for prognostically relevant associations. RESULTS: Analysis of our MALDI imaging data revealed 40 signals in the mass spectra (m/z signals) associated with epithelial structures. The presence of numerous m/z signals was statistically related to one or several phenotypical findings including tumor aggressiveness (stage, grade, or nodal status; 30 signals), solid (5 signals) or papillary (3 signals) growth patterns, and increased (6 signals) or decreased (12 signals) cell proliferation, as determined by Ki-67 immunohistochemistry. Two signals were linked with tumor recurrence in noninvasive (pTa category) tumors, of which one was also related to progression from pTa-category to pT1-category disease. The absence of one m/z signal was linked with decreased survival in the subset of 102 muscle-invasive cancers. CONCLUSION: Our data demonstrate the suitability of combining MSI and large-scale tissue microarrays to simultaneously identify and validate clinically useful molecular markers in urinary bladder cancer. PMID- 25131662 TI - 3D reconstruction of prior beta grains in friction stir-processed Ti-6Al-4V. AB - The prior beta grain structure and orientations in the central stir zone of friction stir-processed Ti-6Al-4V were reconstructed from measured alpha phase orientations obtained by three-dimensional serial sectioning in a dual-beam focused ion beam scanning electron microscope. The data were processed to obtain the alpha colony and beta grain size distributions in the volume. Several beta grains were individually analysed to determine the total number of unique alpha variants and the respective volume fractions of each. The analysis revealed that some grains experienced overwhelming variant selection (i.e. one variant dominated) whereas other beta grains contained a more evenly distributed mixture of all 12 variants. PMID- 25131660 TI - Can we expand active surveillance criteria to include biopsy Gleason 3+4 prostate cancer? A multi-institutional study of 2,323 patients. AB - OBJECTIVE: To test the expandability of active surveillance (AS) to Gleason score 3+4 cancers by assessing the unfavorable disease risk in a large multi institutional cohort. MATERIALS AND METHODS: We performed a retrospective analysis including 2,323 patients with localized Gleason score 3+4 prostate cancer who underwent a radical prostatectomy between 2005 and 2013 from 6 academic centers. We analyzed the rates of biopsy downgrading/upgrading and advanced stage in the overall cohort by employing standardized AS criteria (using biopsy Gleason score 3+4). RESULTS: The final pathologic Gleason score was 3+3 = 6 in 8%, 3+4 = 7 in 67%, 4+3 = 7 in 20%, and 8 to 10 in 5% cases. The overall rate of unfavorable disease (upgrading or advanced stage or both) was 46%. In multivariable analysis, prostate-specific antigen (PSA) level>10 ng/ml, PSA density (PSAD) >0.15 ng/ml/g, clinical stage >T1, and>2 positive cores were predictors of unfavorable disease. According to the AS criteria used, the risk of unfavorable disease ranged from 30% to 42%. In patients without any risk factor (PSA level<= 10 ng/ml, PSAD <= 0.15 ng/ml/g, T1c, and <= 2 positive cores), the unfavorable disease rate was 19%. The main limitations of this study are the retrospective design and nonstandardization of pathologic assessment between centers. CONCLUSIONS: Approximately half of patients with biopsy Gleason score 3+4 cancer have unfavorable disease at final pathology. Nevertheless, expanding AS eligibility to these patients may be acceptable provided adherence to strict selection criteria leading to a<20% risk of unfavorable disease. Future tools for selection such as magnetic resonance imaging, early rebiopsy, and serum markers may be especially beneficial in this group of patients. PMID- 25131663 TI - Catheter ablation for cold water swallowing-induced paroxysmal atrial fibrillation: a case report. PMID- 25131661 TI - Behavior change techniques implemented in electronic lifestyle activity monitors: a systematic content analysis. AB - BACKGROUND: Electronic activity monitors (such as those manufactured by Fitbit, Jawbone, and Nike) improve on standard pedometers by providing automated feedback and interactive behavior change tools via mobile device or personal computer. These monitors are commercially popular and show promise for use in public health interventions. However, little is known about the content of their feedback applications and how individual monitors may differ from one another. OBJECTIVE: The purpose of this study was to describe the behavior change techniques implemented in commercially available electronic activity monitors. METHODS: Electronic activity monitors (N=13) were systematically identified and tested by 3 trained coders for at least 1 week each. All monitors measured lifestyle physical activity and provided feedback via an app (computer or mobile). Coding was based on a hierarchical list of 93 behavior change techniques. Further coding of potentially effective techniques and adherence to theory-based recommendations were based on findings from meta-analyses and meta-regressions in the research literature. RESULTS: All monitors provided tools for self-monitoring, feedback, and environmental change by definition. The next most prevalent techniques (13 out of 13 monitors) were goal-setting and emphasizing discrepancy between current and goal behavior. Review of behavioral goals, social support, social comparison, prompts/cues, rewards, and a focus on past success were found in more than half of the systems. The monitors included a range of 5-10 of 14 total techniques identified from the research literature as potentially effective. Most of the monitors included goal-setting, self-monitoring, and feedback content that closely matched recommendations from social cognitive theory. CONCLUSIONS: Electronic activity monitors contain a wide range of behavior change techniques typically used in clinical behavioral interventions. Thus, the monitors may represent a medium by which these interventions could be translated for widespread use. This technology has broad applications for use in clinical, public health, and rehabilitation settings. PMID- 25131664 TI - Circadian pattern of fibrillatory events in non-Brugada-type idiopathic ventricular fibrillation with a focus on J waves. AB - BACKGROUND: The circadian pattern of ventricular fibrillation (VF) episodes in patients with idiopathic ventricular fibrillation (IVF) is poorly understood. OBJECTIVE: The purpose of this study was to assess the circadian pattern of VF occurrence in patients with IVF. METHODS: Excluding Brugada syndrome and other primary electrical diseases, the circadian pattern of VF occurrence was determined in 64 patients with IVF. The clinical and electrocardiographic characteristics were compared among patients with nocturnal (midnight to 6:00 AM) VF and nonnocturnal VF in relation to J waves. A J wave was defined as either notching or a slur at the QRS terminal >0.1 mV above the isoelectric line in contiguous leads. RESULTS: The overall distribution pattern of VF occurrence showed 2 peaks at approximately 6:00 AM and around 8:00 PM. Nocturnal VF was observed in 20 patients (31.3%), and J waves were present in 14 of these 20 individuals (70.0%), whereas J waves were less frequent in the 44 nonnocturnal patients with VF: 16 (36.4%) (P = .0117). Among patients with J waves, nocturnal VF was observed in 46.7% with a peak at approximately 4:00 AM. Nocturnal VF was less common in patients without J waves, occurring in only 17.6% (P = .0124). Both the type and location of J waves and the pattern of the ST segment were similar between the nocturnal and nonnocturnal VF groups. J waves were associated with a VF storm and long-term arrhythmia recurrence. CONCLUSION: In IVF, the presence of J waves may characterize a higher nocturnal incidence of VF and a higher acute and chronic risk of recurrence. PMID- 25131665 TI - Prospective long-term evaluation of Optim-insulated (Riata ST Optim and Durata) implantable cardioverter-defibrillator leads. AB - BACKGROUND: St Jude Medical Optim-insulated implantable cardioverter defibrillator leads were designed to impart lubricity, strength, and abrasion resistance while maintaining flexibility and biostability. No long-term prospective follow-up data have been published. OBJECTIVE: The objective of this study was to determine the rates of all-cause mechanical failure and its subtypes (conductor fracture, insulation abrasion, externalized conductors, and other mechanical failures) in a prospective cohort of Optim-insulated implantable cardioverter-defibrillator leads. METHODS: St Jude Medical established 3 prospective registries and enrolled 11,016 leads implanted in 10,835 patients beginning in 2006. There was standardized baseline documentation, 6-monthly follow-up, adverse events reports (verified by expert staff using detailed algorithms), and documentation of lead revisions or inactivation, study withdrawal, and death. The Population Health Research Institute (McMaster University) was engaged to review database functions, adjudicate all potential mechanical lead failures, and conduct independent analyses of the data. RESULTS: During a median follow-up of 3.2 years, there were 51 mechanical failures (0.46%), with 99.0% survival free of this outcome by 5 years of follow-up. Freedom from conductor fracture was identified in 99.4% and from all-cause abrasion in 99.8% of the leads, and there were no reports of externalized conductors. There were no significant differences in survival among Durata DF4, Durata DF1, and Riata ST Optim leads. CONCLUSION: Over a mean follow-up of 3.2 years, Optim-insulated leads have low rates of all-cause mechanical failure and no observed externalized conductors. Independent analyses of these registries are designed to provide reliable long-term follow-up information and are ongoing. PMID- 25131666 TI - Clinical and procedural predictors of early complications of ablation for atrial fibrillation: analysis of the national registry data. AB - BACKGROUND: The risk assessment of the complication from atrial fibrillation (AF) ablation is important and needs to be updated. OBJECTIVE: The purpose of this study was to investigate the clinical and procedural factors associated with AF ablation-related early complications. METHODS: The Japanese Heart Rhythm Society invited electrophysiology centers in Japan to register data regarding all AF ablation procedures performed in September 2011, March 2012, and September 2012. Of the 46 putative predictors assessed in the univariate analysis, significant variables (P < .1) were entered into a stepwise logistic regression model for multivariate analysis. RESULTS: Data for 3373 cases were submitted by 165 centers, with 158 early complications reported in 151 patients (4.5%). We identified 13 significant variables in the univariate analysis. Multivariate analysis revealed that 8 (62%) of them were independent predictors of early complications. Female sex (odds ratio and 95% confidence interval 1.6; 1.13 2.27), hypertrophic cardiomyopathy (2.2; 1.08-4.5), valvular heart disease (2.53; 1.28-5.05), deep sedation during the procedure (1.53; 1.09-2.12), and complex fractionated atrial electrocardiogram ablation (1.88; 1.23-2.87) increased early complications. Preprocedural transesophageal echocardiography (0.63; 0.43-0.92), irrigated-tip catheter use (0.46; 0.3-0.69), and periprocedural novel oral anticoagulant use (0.55; 0.32-0.97) decreased them. CONCLUSION: The risk of early complications is increased by female sex, hypertrophic cardiomyopathy, valvular heart disease, deep sedation, and complex fractionated atrial electrocardiogram ablation. It is decreased by preprocedural transesophageal echocardiography, periprocedural novel oral anticoagulant, and irrigated-tip catheter use. PMID- 25131667 TI - Newly detected atrial high rate episodes predict long-term mortality outcomes in patients with permanent pacemakers. AB - BACKGROUND: Subclinical atrial high rate episodes (AHREs) detected by implanted devices in patients with no history of atrial fibrillation (AF) have been associated with an increased risk of stroke and systemic embolism. Data regarding the long-term survival of patients with permanent pacemakers and newly detected AHREs are limited. OBJECTIVE: This study aimed to assess whether newly detected AHREs in pacemaker patients predict mortality outcomes. METHODS: We evaluated 224 patients (mean age 74 +/- 12 years; 118 men [53%]) with no history of AF who underwent dual-chamber pacemaker implantation from 2002 through 2004. During follow-up, patients with AHREs of >=5-minute duration were identified. Mortality data were obtained from the National Death Index. RESULTS: Thirty-nine patients (17%) had AHREs of >=5-minute duration within 6 months of pacemaker implantation. Over a mean follow-up period of 6.6 +/- 2.0 years, the rate of all-cause mortality was 29%. In multivariate analysis adjusted for age, sex, and cardiovascular diseases, AHREs were associated with a significant increase in cardiovascular mortality (hazard ratio [HR] 2.80; 95% confidence interval [CI] 1.24-6.31; P = .013) and stroke mortality (HR 9.65; 95% CI 1.56-59.9; P = .015), with a trend toward increased all-cause mortality (HR 1.79; 95% CI 0.98-3.26; P = .059). The subgroup of patients with AHREs of >=5-minute but <1-day duration still had a significantly increased cardiovascular mortality (HR 3.24; 95% CI 1.37-7.66; P = .007). CONCLUSION: AHREs are commonly encountered in pacemaker patients with no history of AF and are independent predictors of cardiovascular mortality. PMID- 25131668 TI - Trypsinogen activation as observed in accelerated molecular dynamics simulations. AB - Serine proteases are involved in many fundamental physiological processes, and control of their activity mainly results from the fact that they are synthetized in an inactive form that becomes active upon cleavage. Three decades ago Martin Karplus's group performed the first molecular dynamics simulations of trypsin, the most studied member of the serine protease family, to address the transition from the zymogen to its active form. Based on the computational power available at the time, only high frequency fluctuations, but not the transition steps, could be observed. By performing accelerated molecular dynamics (aMD) simulations, an interesting approach that increases the configurational sampling of atomistic simulations, we were able to observe the N-terminal tail insertion, a crucial step of the transition mechanism. Our results also support the hypothesis that the hydrophobic effect is the main force guiding the insertion step, although substantial enthalpic contributions are important in the activation mechanism. As the N-terminal tail insertion is a conserved step in the activation of serine proteases, these results afford new perspective on the underlying thermodynamics of the transition from the zymogen to the active enzyme. PMID- 25131669 TI - Telomerase activation after recruitment in fission yeast. AB - Current models depict that telomerase recruitment equates to activation. Telomeric DNA-binding proteins and the telomerase accessory proteins coordinate the recruitment of telomerase to the ends of chromosomes in a telomere length- and cell-cycle-dependent manner [1-4]. Recent studies have demonstrated that the telomeric protein TPP1 and its binding protein TIN2 are key proteins for both telomerase recruitment and processivity in mammalian cells [5-7]. Although the precise molecular mechanism of telomerase recruitment has not yet been established, targeted point mutations within the oligonucleotide/oligosaccharide binding (OB)-fold domain of TPP1 have been shown to impair telomerase association and processivity [8-10]. In fission yeast, telomerase is recruited through an interaction between the telomerase subunit Est1 and Ccq1, a component of the Pot1 Tpz1 telomere complex (POT1-TPP1 orthologs) [11-15]. Here, we demonstrate that association of telomerase with telomeres does not engage activity. We describe a mutation of Tpz1 that causes critical telomere shortening despite telomeric accumulation of the telomerase catalytic subunit, Trt1. Furthermore, Est1 directed telomerase association with Ccq1 is transient, and the Est1-Ccq1 interaction does not remain the bridge between telomeres and telomerase. Rather, direct interaction of Trt1 with Tpz1 is critical for telomere elongation. Moreover, Ccq1, which has been well characterized as a telomerase recruiter, is also required for the activation of telomere-associated telomerase. Our findings reveal a layer of telomerase regulation that controls activity after recruitment. PMID- 25131670 TI - A bHLH complex activates vascular cell division via cytokinin action in root apical meristem. AB - Higher organisms possess mechanisms to maintain stem cells' proliferative and pluripotent states in stem cell niches [1]. Plants possess two types of stem cell niches in the root and shoot apical meristems, where regulatory interactions exist between stem cells and organizing cells. Recent studies provided new insights into the molecular mechanism of stem cell maintenance [2-4]. However, earlier and more essential developmental events such as the acquisition of stem cell proliferative activity are still unknown. In vascular tissues, procambial cells function as stem cells and differentiate into xylem, phloem, and procambium. Procambial cell proliferation starts at root apical meristem (RAM) postembryonically; therefore, procambial cell development in RAM is a good model for investigating the regulation of stem cell proliferation. LONESOME HIGHWAY (LHW) and TARGET OF MONOPTEROS5 (TMO5), as well as its homolog, TMO5-LIKE1 (T5L1), encode bHLH proteins that function as heterodimers (LHW-TMO5 and LHW T5L1) in vascular tissue organization [5-7]. LHW-T5L1 promotes vascular-cell specific proliferation in RAM [7]. Here, we demonstrate that LHW-T5L1 promotes expression of key cytokinin production genes, including LONELY GUY3 (LOG3) and LOG4, in xylem precursor cells, resulting in elevated cytokinin levels in the surrounding cells. LHW-T5L1 can also promote expression of AHP6, which suppresses cytokinin signaling and then maintains xylem precursor cells at a nondividing state. Our results indicate that LHW-T5L1 establishes xylem precursor cells as a signal center that promotes procambial-cell-specific proliferation through cytokinin response. PMID- 25131672 TI - Presynaptic gain control drives sweet and bitter taste integration in Drosophila. AB - The sense of taste is critical in determining the nutritional suitability of foods. Sweet and bitter are primary taste modalities in mammals, and their behavioral relevance is similar in flies. Sweet taste drives the appetitive response to energy sources, whereas bitter taste drives avoidance of potential toxins and also suppresses the sweet response [1, 2]. Despite their importance to survival, little is known about the neural circuit mechanisms underlying integration of sweet and bitter taste. Here, we describe a presynaptic gain control mechanism in Drosophila that differentially affects sweet and bitter taste channels and mediates integration of these opposing stimuli. Gain control is known to play an important role in fly olfaction, where GABAB receptor (GABABR) mediates intra- and interglomerular presynaptic inhibition of sensory neuron output [3-5]. In the taste system, we find that gustatory receptor neurons (GRNs) responding to sweet compounds express GABABR, whereas those that respond to bitter do not. GABABR mediates presynaptic inhibition of calcium responses in sweet GRNs, and both sweet and bitter stimuli evoke GABAergic neuron activity in the vicinity of GRN axon terminals. Pharmacological blockade and genetic reduction of GABABR both lead to increased sugar responses and decreased suppression of the sweet response by bitter compounds. We propose a model in which GABA acts via GABABR to expand the dynamic range of sweet GRNs through presynaptic gain control and suppress the output of sweet GRNs in the presence of opposing bitter stimuli. PMID- 25131671 TI - Enhancing perception of contaminated food through acid-mediated modulation of taste neuron responses. AB - BACKGROUND: Natural foods contain not only nutrients, but also nonnutritious and potentially harmful chemicals. Thus, animals need to evaluate food content in order to make adequate feeding decisions. RESULTS: Here, we investigate the effects of acids on the taste neuron responses and on taste behavior of desirable, nutritious sugars and sugar/bitter compound mixtures in Drosophila melanogaster. Using Ca2+ imaging, we show that acids activate neither sweet nor bitter taste neurons in tarsal taste sensilla. However, they suppress responses to bitter compounds in bitter-sensing neurons. Moreover, acids reverse suppression of bitter compounds exerted on sweet-sensing neurons. Consistent with these observations, behavioral analyses show that bitter-compound-mediated inhibition on feeding behavior is alleviated by acids. To investigate the cellular mechanism by which acids modulate these effects, we silenced bitter sensing gustatory neurons. Surprisingly, this intervention had little effect on acid-mediated derepression of sweet neuron or feeding responses to either sugar/bitter compound mixtures or sugar/bitter compound/acid mixtures, suggesting that there are two independent pathways by which bitter compounds are sensed. CONCLUSIONS: Our investigations reveal that acids, when presented in dietary relevant concentrations, enhance the perception of sugar/bitter compound mixtures. Drosophila's natural food sources-fruits and cohabitating yeast-are rich in sugars and acids but are rapidly colonized by microorganisms, such as fungi, protozoan parasites, and bacteria, many of which produce bitter compounds. We propose that the acids present in most fruits counteract the inhibitory effects of these bitter compounds during feeding. PMID- 25131673 TI - Antibiotic treatment selects for cooperative virulence of Salmonella typhimurium. AB - Antibiotics are powerful therapeutics but are not equally effective against all cells in bacterial populations. Bacteria that express an antibiotic-tolerant phenotype ("persisters") can evade treatment [1]. Persisters can cause relapses of the infection after the end of the therapy [2]. It is still poorly understood whether persistence affects the evolution of bacterial virulence. During infections, persisters have been found preferentially at particular sites within the host [3, 4]. If bacterial virulence factors are required to reach such sites, treatment with antibiotics could impose selection on the expression of virulence genes, in addition to their well-established effects on bacterial resistance. Here, we report that treatment with antibiotics selects for virulence and fosters transmissibility of Salmonella Typhimurium. In a mouse model for Salmonella diarrhea, treatment with the broad-spectrum antibiotic ciprofloxacin reverses the outcome of competition between wild-type bacteria and avirulent mutants that can spontaneously arise during within-host evolution [5]. While avirulent mutants take over the gut lumen and abolish disease transmission in untreated mice, ciprofloxacin tilts the balance in favor of virulent, wild-type bacteria. This is explained by the need for virulence factors to invade gut tissues and form a persistent reservoir. Avirulent mutants remain in the gut lumen and are eradicated. Upon cessation of antibiotic treatment, tissue-lodged wild-type pathogens reseed the gut lumen and thereby facilitate disease transmissibility to new hosts. Our results suggest a general principle by which antibiotic treatment can promote cooperative virulence during within-host evolution, increase duration of transmissibility, and thereby enhance the spread of an infectious disease. PMID- 25131674 TI - Endogenous species of mammalian nonmuscle myosin IIA and IIB include activated monomers and heteropolymers. AB - BACKGROUND: Class II myosins generate contractile forces in cells by polymerizing into bipolar filaments and pulling on anchored actin filaments. Nonmuscle myosin II (NMII) plays central roles during cell adhesion, migration, cytokinesis, and tissue morphogenesis. NMII is present in virtually all mammalian cell types as tissue-specific combinations of NMIIA, NMIIB, and NMIIC isoforms. It remains poorly understood how the highly dynamic NMII-actin contractile system begins to assemble at new cellular locations during cell migration and how incorporation of different NMII isoforms into this system is coordinated. RESULTS: Using platinum replica electron microscopy in combination with immunogold labeling, we demonstrate that individual activated (phosphorylated on the regulatory light chain and unfolded) NMIIA and NMIIB molecules represent a functional form of NMII in motile cells and that NMIIA and NMIIB copolymerize into nascent bipolar filaments during contractile system assembly. Using subdiffraction stimulated emission depletion microscopy together with a pharmacological block-and-release approach, we report that NMIIA and NMIIB simultaneously incorporate into the cytoskeleton during initiation of contractile system assembly, whereas the characteristic rearward shift of NMIIB relative to NMIIA is established later in the course of NMII turnover. CONCLUSIONS: We show existence of activated NMII monomers in cells, copolymerization of endogenous NMIIA and NMIIB molecules, and contribution of both isoforms, rather than only NMIIA, to early stages of the contractile system assembly. These data change the current paradigms about dynamics and functions of NMII and provide new conceptual insights into the organization and dynamics of the ubiquitous cellular machinery for contraction that acts in multiple cellular contexts. PMID- 25131676 TI - Individual behaviors dominate the dynamics of an urban mountain lion population isolated by roads. AB - Large carnivores can be particularly sensitive to the effects of habitat fragmentation on genetic diversity [1, 2]. The Santa Monica Mountains (SMMs), a large natural area within Greater Los Angeles, is completely isolated by urban development and the 101 freeway to the north. Yet the SMMs support a population of mountain lions (Puma concolor), a very rare example of a large carnivore persisting within the boundaries of a megacity. GPS locations of radio-collared lions indicate that freeways are a near-absolute barrier to movement. We genotyped 42 lions using 54 microsatellite loci and found that genetic diversity in SMM lions, prior to 2009, was lower than that for any population in North America except in southern Florida, where inbreeding depression led to reproductive failure [3-5]. We document multiple instances of father-daughter inbreeding and high levels of intraspecific strife, including the unexpected behavior of a male killing two of his offspring and a mate and his son killing two of his brothers. Overall, no individuals from the SMMs have successfully dispersed. Gene flow is critical for this population, and we show that a single male immigrated in 2009, successfully mated, and substantially enhanced genetic diversity. Our results imply that individual behaviors, most likely caused by limited area and reduced opportunities to disperse, may dominate the fate of small, isolated populations of large carnivores. Consequently, comprehensive behavioral monitoring can suggest novel solutions for the persistence of small populations, such as the transfer of individuals across dispersal barriers. PMID- 25131675 TI - Self-generated movements with "unexpected" sensory consequences. AB - The nervous systems of diverse species, including worms and humans, possess mechanisms for distinguishing between sensations arising from self-generated (i.e., expected) movements from those arising from other-generated (i.e., unexpected) movements [1-3]. To make this critical distinction, animals generate copies, or corollary discharges, of motor commands [4, 5]. Corollary discharge facilitates the selective gating of reafferent signals arising from self generated movements, thereby enhancing detection of novel stimuli [6-10]. However, for a developing nervous system, such sensory gating would be counterproductive if it impedes transmission of the very activity upon which activity-dependent mechanisms depend [11]. In infant rats during active (or REM) sleep--a behavioral state that predominates in early infancy [12-16]--neural circuits within the brainstem [17, 18] trigger hundreds of thousands of myoclonic twitches each day [19]. The putative contribution of these self-generated movements to the activity-dependent development of the sensorimotor system is supported by the observation that reafference from twitching limbs reliably and substantially triggers brain activity [20-23]. In contrast, under identical testing conditions, even the most vigorous wake movements reliably fail to trigger reafferent brain activity [21-23]. One hypothesis that accounts for this paradox is that twitches, uniquely among self-generated movements, lack corollary discharge [23]. Here, we test this hypothesis in newborn rats by manipulating the degree to which self-generated movements are expected and, therefore, their presumed recruitment of corollary discharge. We show that twitches, although self generated, are processed as if they are unexpected. PMID- 25131677 TI - Gating characteristics control glutamate receptor distribution and trafficking in vivo. AB - Glutamate-releasing synapses dominate excitatory release in the brain. Mechanisms governing their assembly are of major importance for circuit development and long term plasticity underlying learning and memory. AMPA/Kainate-type glutamate receptors (GluRs) are tetrameric ligand-gated ion channels that open their ion conducting pores in response to binding of the neurotransmitter. Changes in subunit composition of postsynaptic GluRs are highly relevant for plasticity and development of glutamatergic synapses [1-4]. To date, posttranslational modifications, mostly operating via the intracellular C-terminal domains (CTDs) of GluRs, are presumed to be the major regulator of trafficking [5]. In recent years, structural and electrophysiological analyses have improved our understanding of GluR gating mechanism [6-11]. However, whether conformational changes subsequent to glutamate binding may per se be able to influence GluR trafficking has remained an unaddressed question. Using a Drosophila system allowing for extended visualization of GluR trafficking in vivo, we here provide evidence that mutations changing the gating behavior alter GluR distribution and trafficking. GluR mutants associated with reduced charge transfer segregated from coexpressed wild-type GluRs on the level of individual postsynaptic densities. Segregation was lost upon blocking of evoked glutamate release. Photobleaching experiments suggested increased mobility of mutants with reduced charge transfer, which accumulated prematurely during early steps of synapse assembly, but failed to further increase their level in accordance with assembly of the presynaptic scaffold. In summary, gating characteristics seem to be a new variable for the understanding of GluR trafficking relevant to both development and plasticity. PMID- 25131678 TI - Combined TMS and FMRI reveal dissociable cortical pathways for dynamic and static face perception. AB - Faces contain structural information, for identifying individuals, as well as changeable information, which can convey emotion and direct attention. Neuroimaging studies reveal brain regions that exhibit preferential responses to invariant [1, 2] or changeable [3-5] facial aspects but the functional connections between these regions are unknown. We addressed this issue by causally disrupting two face-selective regions with thetaburst transcranial magnetic stimulation (TBS) and measuring the effects of this disruption in local and remote face-selective regions with functional magnetic resonance imaging (fMRI). Participants were scanned, over two sessions, while viewing dynamic or static faces and objects. During these sessions, TBS was delivered over the right occipital face area (rOFA) or right posterior superior temporal sulcus (rpSTS). Disruption of the rOFA reduced the neural response to both static and dynamic faces in the downstream face-selective region in the fusiform gyrus. In contrast, the response to dynamic and static faces was doubly dissociated in the rpSTS. Namely, disruption of the rOFA reduced the response to static but not dynamic faces, while disruption of the rpSTS itself reduced the response to dynamic but not static faces. These results suggest that dynamic and static facial aspects are processed via dissociable cortical pathways that begin in early visual cortex, a conclusion inconsistent with current models of face perception [6-9]. PMID- 25131680 TI - (NH4)2SO4 recovery from liquid side streams. AB - Two methods of recovering nitrogen from liquid side streams are presented in this paper. The first method was demonstrated at an ammonia stripping plant treating 5 7 m(3)/h sludge water at the wastewater treatment plant (WWTP) Kloten-Opfikon (CH). In addition to the usual stripping and scrubbing columns, a third column had been added in order strip CO2, thus reducing the NaOH-demand of the subsequent ammonia stripping. At first, just the stripping plant was put into operation and optimized without any pre-treatment of the supernatant. Next, the CO2-stripper column was activated and optimized by gas measurements to minimize free ammonia losses, heat losses, and energy consumption. Key operational aspects of the plant were evaluated. Finally, up to 1.4 m(3)/h source-separated urine was successfully fed into the stripping facility. The second ammonia removal method using hydrophobic hollow fiber membranes was tested in two small pilot systems by different manufacturers in 2012 and 2013 at WWTP Neugut. In this technology, free ammonia gas in the sludge liquid diffuses at pH >9.3 from the sludge liquid through the air-filled pores of the microporous hydrophobic membrane into concentrated sulfuric acid flowing through the hollow fibers, forming ammonium sulfate. The small pore size and the hydrophobic nature of the membrane prevent the liquid phase from entering into the pores due to the surface tension effect. Practical experience regarding operational parameters like wastewater flow rate, pH, temperature, ammonia concentration, fouling and precipitations processes, optimal flow schemes, and process configurations was collected. PMID- 25131679 TI - Does a short-term exposure to cadmium chloride affects haemocyte parameters of the marine gastropod Haliotis tuberculata? AB - In this study, a model based on primary cultured haemocytes from the gastropod mollusc Haliotis tuberculata was established to investigate the effects of cadmium chloride in vitro. Cells were exposed for 24 h to CdCl2 concentrations of 0, 1 and 100 MUg ml(-1). The effects of cadmium on haemocyte parameters were investigated using morphological, spectrophotometric and flow cytometry analysis. Results showed that cadmium has no significant effects on cell viability and phagocytotic activity under the tested conditions. However, haemocytes became more rounded after cadmium exposure, which could explain the significant decrease of cell area beginning at 1 MUg ml(-1) of CdCl2. PMID- 25131681 TI - Molecular markers in ambient aerosol in the Mahanadi Riverside Basin of eastern central India during winter. AB - Organic molecular markers are important atmospheric constituents. Their formation and sources are important aspects of the study of urban and rural air quality. We collected PM10 aerosol samples from the Mahanadi Riverside Basin (MRB), a rural part of eastern central India, during the winter of 2011. PM10 aerosols were characterized for molecular markers using ion chromatography. The concentration of PM10 ranged from 208.8 to 588.3 MUg m(-3) with a mean concentration of 388.9 MUg m(-3). Total concentration of anhydrosugars, sugar alcohols, primary sugars, and oxalate were found to be 3.25, 5.60, 10.52, and 0.37 MUg m(-3), respectively, during the study period. Glucose was the most abundant species followed by levoglucosan and mannitol. Significant positive correlation between the molecular markers, anhydrosugars, sugar alcohols, primary sugars, and oxalic acid confirmed that biomass burning, biogenic activity, and re-suspension of soil particles were the main sources of aerosol in the eastern central India study area. PMID- 25131682 TI - Multiple linear regression model for bromate formation based on the survey data of source waters from geographically different regions across China. AB - A total of 86 source water samples from 38 cities across major watersheds of China were collected for a bromide (Br(-)) survey, and the bromate (BrO3 (-)) formation potentials (BFPs) of 41 samples with Br(-) concentration >20 MUg L(-1) were evaluated using a batch ozonation reactor. Statistical analyses indicated that higher alkalinity, hardness, and pH of water samples could lead to higher BFPs, with alkalinity as the most important factor. Based on the survey data, a multiple linear regression (MLR) model including three parameters (alkalinity, ozone dose, and total organic carbon (TOC)) was established with a relatively good prediction performance (model selection criterion = 2.01, R (2) = 0.724), using logarithmic transformation of the variables. Furthermore, a contour plot was used to interpret the influence of alkalinity and TOC on BrO3 (-) formation with prediction accuracy as high as 71 %, suggesting that these two parameters, apart from ozone dosage, were the most important ones affecting the BFPs of source waters with Br(-) concentration >20 MUg L(-1). The model could be a useful tool for the prediction of the BFPs of source water. PMID- 25131683 TI - Ecocatalysis for 2H-chromenes synthesis: an integrated approach for phytomanagement of polluted ecosystems. AB - A direct, general and efficient method to synthesize 2H-chromenes (2H benzo[b]pyrans), identified as environmentally friendly pesticides, has been developed. This approach lays on the new concept of ecocatalysis, which involves the use of biomass from phytoextraction processes, as a valuable source of metallic elements for chemical synthesis. This methodology is similar or superior to known methods, affording 2H-chromenes with good to excellent yields (60-98%), including the preparation of precocene I, a natural insect growth regulator, with 91% yield. The approach is ideal for poor reactive substrates such as phenol or naphthol, classically transformed into 2H-chromenes by methodologies associated with environmental issues. These results illustrate the interest of combining phytoextraction and green synthesis of natural insecticides. PMID- 25131684 TI - Quasi-simultaneous in-line flue gas monitoring of NO and NO2 emissions at a caloric power plant employing mid-IR laser spectroscopy. AB - Two pulsed thermoelectrically cooled mid-infrared distributed feedback quantum cascade lasers (QCLs) were used for the quasi-simultaneous in-line determination of NO and NO2 at the caloric power plant Durnrohr (Austria). The QCL beams were combined using a bifurcated hollow fiber, sent through the flue tube (inside diameter: 5.5 m), reflected by a retro-reflector and recorded using a fast thermoelectrically cooled mercury-cadmium-telluride detector. The thermal chirp during 300 ns pulses was about 1.2 cm(-1) and allowed scanning of rotational vibrational doublets of the analytes. On the basis of the thermal chirp and the temporal resolution of data acquisition, a spectral resolution of approximately 0.02 cm(-1) was achieved. The recorded rotational vibrational absorption lines were centered at 1900 cm(-1) for NO and 1630 cm(-1) for NO2. Despite water content in the range of 152-235 g/m(3) and an average particle load of 15.8 mg/m(3) in the flue gas, in-line measurements were possible achieving limits of detection of 73 ppb for NO and 91 ppb for NO2 while optimizing for a single analyte. Quasi-simultaneous measurements resulted in limits of detection of 219 ppb for NO and 164 ppb for NO2, respectively. Influences of temperature and pressure on the data evaluation are discussed, and results are compared to an established reference method based on the extractive measurements presented. PMID- 25131686 TI - A tribute to Dr. Steve Haskins. PMID- 25131685 TI - Relative value of ultrasound, computed tomography and positron emission tomography imaging in the clinically node-negative neck in oral cancer. AB - AIM: To determine the most accurate noninvasive imaging modality for occult metastasis in clinically node-negative necks in oral squamous cell carcinoma from a granulomatous disease endemic region. METHOD: Prospective, observational study comparing ultrasound (US), contrast enhanced computed tomography (CECT) and positron emission tomography-computed tomography (PET-CT). Level wise assessment of neck nodes with each imaging modality was performed and compared with final histopathology. RESULTS: Eighty-five necks were evaluated in 70 patients. Sensitivity, specificity and accuracy of the three modalities were 78.9, 68.75 and 73.25% for US, 73.6, 85.4 and 80.2% for CECT, and 81.5, 54.1 and 66.2% for PET-CT, respectively. CECT performed better than US and PET-CT scan particularly in levels IB and II (accuracy of 81.4 and 88.3% for CECT, 73.25 and 79.1% for US, and 68.6 and 68.6% for PET-CT scan, respectively). Concordance with histology was best with CECT (kappa = 0.615) followed by US (kappa = 0.461) and PET-CT (kappa = 0.337). CONCLUSION: The quest for the most accurate imaging modality in clinically node-negative necks continues. US alone is inadequate. While PET-CT may not be a specific imaging modality in detecting occult cervical nodal metastasis in endemic regions of chronic granulomatous diseases, the performance of PET CECT in this setting remains to be evaluated. CECT scan, routinely used in imaging for primary disease, is fairly accurate in detecting nodal metastasis. However, in early oral cancers that are generally treated without any imaging for the primary tumor, management of the neck will largely depend on clinical judgment. PMID- 25131687 TI - Prevalence of celiac disease autoimmunity in children with type 1 diabetes: regional variations across the Oresund strait between Denmark and southernmost Sweden. AB - OBJECTIVES: The aim was to determine the prevalence of celiac disease autoimmunity in children with type 1 diabetes (T1D) diagnosed in Denmark and Sweden. METHODS: A total of 662 Swedish children with T1D were matched with 1080 Danish children with T1D and 309 healthy children from Sweden and 283 from Denmark served as controls. Sera were analyzed for the presence of IgA and IgG (IgAG) autoantibodies against deamidated gliadin peptide (DGP) and tissue transglutaminase (tTG) with enzyme-linked immunosorbent assay (ELISA) and IgG-tTG separately in a radioligand binding assay (RBA). Human leukocyte antigen (HLA) DQB1 and DQA1 genotyping were determined in the T1D cohorts. RESULTS: In the Swedish T1D cohort, 17.2% (114/662) were IgAG-DGP/tTG positive compared with 11.7% (126/1080) in the Danish T1D cohort (p = 0.001) and with 9.4% (29/309) Swedish (p = 0.001) and 5.7% (16/283) Danish (p = 0.003) controls. In the Swedish T1D cohort, both levels of IgAG-DGP/tTG and IgG-tTG were higher compared with the levels in the Danish T1D (p < 0.001). In the control group, 2.8% of the Danish children were positive for both IgAG-DGP/tTG and IgG-tTG, compared to 0.3% of the Swedish. Presence of HLA-DQ2 was equally distributed among 89 children with T1D positive for both IgAG-DGP/tTG and IgG-tTG. CONCLUSION: The discrepancy in levels of IgAG-DGP/tTG and IgG-tTG between Swedish and Danish T1D cohorts was independent of HLA and suggests that regional variations in comorbidity of celiac disease in T1D is caused by difference in exposure to environmental factors. PMID- 25131688 TI - Improving sensitivity for serodiagnosis of tuberculosis using TB16.3-echA1 fusion protein. AB - This study aimed at developing and assessing the fusion proteins with enhanced sensitivity to detect antibodies in plasma as a diagnostic method for tuberculosis. DNA fragments encoding TB16.3 and echA1 gene regions corresponding to proteins TB16.3 and echA1 from Mycobacterium tuberculosis were amplified through PCR. Through a series of restrictions and ligations two novel fusion constructs TB16.3-echA1 and TB16.3-tnPstS1 were produced and expressed in Escherichia coli. These were screened for detection of antibodies in human plasma. The individual antigens TB16.3, echA1 and tnPstS1 and the fusion protein TB16.3-tnPstS1 and TB16.3-echA1 showed sensitivities of 29%, 25.5%, 42.8%, 40.0% and 47.2%, respectively. Lower sensitivity in case of TB16.3-tnPstS1 seems to be due to the structural arrangement between the two proteins, which is likely to mask several of their epitopes. The higher sensitivity of TB16.3-echA1 appears to be due to lesser interaction between the two proteins thus allowing free availability of epitopes for binding antibodies. 64% of TB patients were found positive for either one of the two fusion proteins TB16.3-echA1 and TB16.3 tnPstS1. This study indicates that the novel fusion protein TB16.3-echA1 has a potential in serodiagnosis of TB with improved sensitivity and reliability. PMID- 25131689 TI - Tanycytes: a gateway to the metabolic hypothalamus. AB - The central regulation of energy balance relies on the ability of the brain to promptly and efficiently sense variations of metabolic state. To achieve this, circulating hormonal and metabolic signals have to cross the blood-brain interface, where unusual glial cells named tanycytes have been described to play a key role in this process. Tanycytes are specialised polarised ependymoglial cells that line the floor of the third ventricle and send a single process to contact hypothalamic neurones and blood vessels. Although their role in the regulation of energy balance via the modulation of neuronal activity or their chemosensitivity has been already described, recent studies ascribe a new function to tanycytes in the regulation of energy homeostasis as a result of their capacity to regulate the access of metabolic signals to the hypothalamus. This review discusses the peculiar place of tanycytes within the blood hypothalamus interface, as well as a striking capacity to remodel their own interface to ensure an adaptive metabolic response to energy imbalances. PMID- 25131690 TI - Resting-state functional connectivity of the human hypothalamus. AB - The hypothalamus is of enormous importance for multiple bodily functions such as energy homeostasis. Especially, rodent studies have greatly contributed to our understanding how specific hypothalamic subregions integrate peripheral and central signals into the brain to control food intake. In humans, however, the neural circuitry of the hypothalamus, with its different subregions, has not been delineated. Hence, the aim of this study was to map the hypothalamus network using resting-state functional connectivity (FC) analyses from the medial hypothalamus (MH) and lateral hypothalamus (LH) in healthy normal-weight adults (n = 49). Furthermore, in a separate sample, we examined differences within the LH and MH networks between healthy normal-weight (n = 25) versus overweight/obese adults (n = 23). FC patterns from the LH and MH revealed significant connections to the striatum, thalamus, brainstem, orbitofrontal cortex, middle and posterior cingulum and temporal brain regions. However, our analysis revealed subtler distinctions within hypothalamic subregions. The LH was functionally stronger connected to the dorsal striatum, anterior cingulum, and frontal operculum, while the MH showed stronger functional connections to the nucleus accumbens and medial orbitofrontal cortex. Furthermore, overweight/obese participants revealed heightened FC in the orbitofrontal cortex and nucleus accumbens within the MH network. Our results indicate that the MH and LH network are tapped into different parts of the dopaminergic circuitry of the brain, potentially modulating food reward based on the functional connections to the ventral and dorsal striatum, respectively. In obese adults, FC changes were observed in the MH network. PMID- 25131693 TI - Inhibition of angiotensin-converting enzyme increases oestradiol production in ewes submitted to oestrous synchronization protocol. AB - This study aimed at evaluating the effects of angiotensin-converting enzyme inhibitor (enalapril) and angiotensin II antagonist (valsartan) on the oestradiol and progesterone production in ewes submitted to oestrous synchronization protocol. The animals were weighed and randomly divided into three groups (n = 7). A pre-experiment conducted to verify the effectiveness and toxicity of enalapril (0.5 mg/kg LW) and valsartan (2.2 mg/kg LW) showed that, in the doses used, these drugs were effective in reducing blood pressure without producing toxic effects. In the experiment, all animals were subjected to oestrous synchronization protocol during 12 days. On D10, D11 and D12, animals received saline, enalapril or valsartan (same doses of the pre-experiment), according to the group randomly divided. The hormonal analysis showed an increase in oestradiol on the last day of the protocol (D12) in animals that received enalapril (p < 0.05), but not in other groups, without changing the concentration of progesterone in any of the treatments. It is concluded that valsartan and enalapril are safe and effective subcutaneously for use in sheep and that the angiotensin-converting enzyme (ACE) inhibition with enalapril leads to an increase in oestradiol production near ovulation without changing the concentration of progesterone. This shows that ACE inhibition may be a useful tool in reproductive biotechnologies involving induction and synchronization of oestrus and ovulation in sheep. PMID- 25131694 TI - The iPod binocular home-based treatment for amblyopia in adults: efficacy and compliance. AB - BACKGROUND: Occlusion therapy for amblyopia is predicated on the idea that amblyopia is primarily a disorder of monocular vision; however, there is growing evidence that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression. Furthermore, we have found that a dichoptic treatment intervention designed to directly target suppression can result in clinically significant improvement in both binocular and monocular visual function in adult patients with amblyopia. The fact that monocular improvement occurs in the absence of any fellow eye occlusion suggests that amblyopia is, in part, due to chronic suppression. Previously the treatment has been administered as a psychophysical task and more recently as a video game that can be played on video goggles or an iPod device equipped with a lenticular screen. The aim of this case-series study of 14 amblyopes (six strabismics, six anisometropes and two mixed) ages 13 to 50 years was to investigate: 1. whether the portable video game treatment is suitable for at-home use and 2. whether an anaglyphic version of the iPod-based video game, which is more convenient for at home use, has comparable effects to the lenticular version. METHODS: The dichoptic video game treatment was conducted at home and visual functions assessed before and after treatment. RESULTS: We found that at-home use for 10 to 30 hours restored simultaneous binocular perception in 13 of 14 cases along with significant improvements in acuity (0.11 +/- 0.08 logMAR) and stereopsis (0.6 +/- 0.5 log units). Furthermore, the anaglyph and lenticular platforms were equally effective. In addition, the iPod devices were able to record a complete and accurate picture of treatment compliance. CONCLUSION: The home-based dichoptic iPod approach represents a viable treatment for adults with amblyopia. PMID- 25131695 TI - Contemporary evidence-based guidelines: practice based on the strongest evidence. PMID- 25131692 TI - Mutant disrupted-in-schizophrenia 1 in astrocytes: focus on glutamate metabolism. AB - Disrupted-in-schizophrenia 1 (DISC1) is a genetic risk factor that has been implicated in major mental disorders. DISC1 binds to and stabilizes serine racemase to regulate production of D-serine by astrocytes, contributing to glutamate (GLU) neurotransmission. However, the possible involvement of astrocytic DISC1 in synthesis, metabolism, reuptake, or secretion of GLU remains unexplored. Therefore, we studied the effects of dominant-negative mutant DISC1 on various aspects of GLU metabolism by using primary astrocyte cultures and hippocampal tissue from transgenic mice with astrocyte-restricted expression of mutant DISC1. Although mutant DISC1 had no significant effects on astrocyte proliferation, GLU reuptake, glutaminase, or glutamate carboxypeptidase II activity, expression of mutant DISC1 was associated with increased levels of alanine-serine-cysteine transporter 2, vesicular glutamate transporters 1 and 3 in primary astrocytes and in the hippocampus, and elevated expression of the NR1 subunit and diminished expression of the NR2A subunit of N-methyl-D-aspartate (NMDA) receptors in the hippocampus, at postnatal day 21. Our findings indicate that decreased D-serine production by astrocytic mutant DISC1 might lead to compensatory changes in levels of the amino acid transporters and NMDA receptors in the context of tripartite synapse. PMID- 25131696 TI - A perspective on the New American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment. AB - The recently published American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for cardiovascular risk assessment provide equations to estimate the 10-year and lifetime atherosclerotic cardiovascular disease (ASCVD) risk in African Americans and non-Hispanic whites, include stroke as an adverse cardiovascular outcome, and emphasize shared decision making. The guidelines provide a valuable framework that can be adapted on the basis of clinical judgment and individual/institutional expertise. In this review, we provide a perspective on the new guidelines, highlighting what is new, what is controversial, and potential adaptations. We recommend obtaining family history of ASCVD at the time of estimating ASCVD risk and consideration of imaging to assess subclinical disease burden in patients at intermediate risk. In addition to the adjuncts for ASCVD risk estimation recommended in the guidelines, measures that may be useful in refining risk estimates include carotid ultrasonography, aortic pulse wave velocity, and serum lipoprotein(a) levels. Finally, we stress the need for research efforts to improve assessment of ASCVD risk given the suboptimal performance of available risk algorithms and suggest potential future directions in this regard. PMID- 25131691 TI - Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis. AB - I review how diverse inherited and acquired abnormalities in epidermal structural and enzymatic proteins converge to produce defective permeability barrier function and antimicrobial defense in patients with atopic dermatitis (AD). Although best known are mutations in filaggrin (FLG), mutations in other member of the fused S-100 family of proteins (ie, hornerin [hrn] and filaggrin 2 [flg 2]); the cornified envelope precursor (ie, SPRR3); mattrin, which is encoded by TMEM79 and regulates the assembly of lamellar bodies; SPINK5, which encodes the serine protease inhibitor lymphoepithelial Kazal-type trypsin inhibitor type 1; and the fatty acid transporter fatty acid transport protein 4 have all been linked to AD. Yet these abnormalities often only predispose to AD; additional acquired stressors that further compromise barrier function, such as psychological stress, low ambient humidity, or high-pH surfactants, often are required to trigger disease. T(H)2 cytokines can also compromise barrier function by downregulating expression of multiple epidermal structural proteins, lipid synthetic enzymes, and antimicrobial peptides. All of these inherited and acquired abnormalities converge on the lamellar body secretory system, producing abnormalities in lipid composition, secretion, and/or extracellular lamellar membrane organization, as well as antimicrobial defense. Finally, I briefly review therapeutic options that address this new pathogenic paradigm. PMID- 25131697 TI - A summary and critical assessment of the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: filling the gaps. AB - The American College of Cardiology/American Heart Association (ACC/AHA) Task Force on Practice Guidelines has recently released the new cholesterol treatment guideline. This update was based on a systematic review of the evidence and replaces the previous guidelines from 2002 that were widely accepted and implemented in clinical practice. The new cholesterol treatment guideline emphasizes matching the intensity of statin treatment to the level of atherosclerotic cardiovascular disease (ASCVD) risk and replaces the old paradigm of pursuing low-density lipoprotein cholesterol targets. The new guideline also emphasizes the primacy of the evidence base for statin therapy for ASCVD risk reduction and lists several patient groups that will not benefit from statin treatment despite their high cardiovascular risk, such as those with heart failure (New York Heart Association class II-IV) and patients undergoing hemodialysis. The guideline has been received with mixed reviews and significant controversy. Because of the evidence-based nature of the guideline, there is room for several questions and uncertainties on when and how to use lipid-lowering therapy in clinical practice. The goal of the Mayo Clinic Task Force in the assessment, interpretation, and expansion of the ACC/AHA cholesterol treatment guideline is to address gaps in information and some of the controversial aspects of the newly released cholesterol management guideline using additional sources of evidence and expert opinion as needed to guide clinicians on key aspects of ASCVD risk reduction. PMID- 25131698 TI - Pattern and factors associated with utilization of dental services among older adults in rural Victoria. AB - BACKGROUND: In Australia, rural and regional areas have an increased proportion of older people who are ageing more rapidly than their metropolitan counterparts. This increase in the ageing population and its uneven geographic distribution is likely to pose an oral health challenge in the near future. METHODS: A cross sectional study conducted in a sample of 226 community-dwelling adults aged 55 years and older, living in the City of Greater Bendigo who completed a questionnaire and received an oral examination. RESULTS: Overall, 51.2% of participants reported having been to the dentist in the previous 12 months. Reported barriers to dental care were: cost of services (32.7%), fear of dentists (25.8%), length of waiting lists (18.1%) and availability of oral health care services (11.1%). Living alone, gender, low income, lack of education, low self perceived oral health needs, self-perceived barriers, edentulism, and presence of mobility problems were statistically significant variables associated with less use of dental services (p < 0.0001). CONCLUSIONS: Access to dental care is affected by financial and structural barriers as well as other predisposing and enabling factors among older adults. Thus, increase in user services will require efforts to reduce financial barriers and make dental care culturally and linguistically competent. PMID- 25131699 TI - Minimally invasive neurosurgical access techniques to facilitate endovascular treatment of dural arteriovenous fistulae. AB - We report two cases of dural arteriovenous fistulae treated endovascularly, where percutaneous venous or arterial access was not suitable. In both cases, a different surgical access technique was used to allow transcranial cannulation of the appropriate venous sinus or of the varix to gain access and occlude the fistula. PMID- 25131700 TI - Visualizing an ultra-weak protein-protein interaction in phosphorylation signaling. AB - Proteins interact with each other to fulfill their functions. The importance of weak protein-protein interactions has been increasingly recognized. However, owing to technical difficulties, ultra-weak interactions remain to be characterized. Phosphorylation can take place via a K(D)~25 mM interaction between two bacterial enzymes. Using paramagnetic NMR spectroscopy and with the introduction of a novel Gd(III)-based probe, we determined the structure of the resulting complex to atomic resolution. The structure accounts for the mechanism of phosphoryl transfer between the two enzymes and demonstrates the physical basis for their ultra-weak interaction. Further, molecular dynamics (MD) simulations suggest that the complex has a lifetime in the micro- to millisecond regimen. Hence such interaction is termed a fleeting interaction. From mathematical modeling, we propose that an ultra-weak fleeting interaction enables rapid flux of phosphoryl signal, providing a high effective protein concentration. PMID- 25131702 TI - Young chemists and the European Young Chemist Award. PMID- 25131701 TI - Gamma Glutamyl Transferase Activity is Associated With Both Paraoxonase Activity and Aortic Stiffness in Hypertensive Patients. AB - BACKGROUND: We aimed to investigate relationship between gamma glutamyl transferase (GGT) activity with paraoxonase 1 (PON1) activity and aortic stiffness (AS) parameters such as pulse wave velocity (PWV) and augmentation index (AIx). METHODS: Measurements were obtained from 324 patients with newly diagnosed essential hypertension (mean age: 55.0 +/- 8.2 years). The patients were divided into two groups according to their median GGT values. PWV and AIx were calculated using the single-point method via the Mobil-O-Graph(r) ARCsolver algorithm. RESULTS: PWV, Aix, and high-sensitive C-reactive protein (hs-CRP) values were higher and PON1 activity values were lower in GGThigh group compared with GGTlow group (P < 0.05, for all). Multiple linear regression analysis showed that GGT activity was independently associated with PWV (beta = 0.496, P < 0.001) and PON1 activity (beta = -0.343, P < 0.001) as well as hs-CRP (beta = 0.334, P < 0.001). CONCLUSION: These results may support that increased GGT activity would be associated with both impaired antioxidant system and increased AS in hypertensive patients. PMID- 25131705 TI - Identification of the novel KIR2DL3*030 allele from a southern Chinese Han individual. AB - KIR2DL3*030 differs from the closest allele, KIR2DL3*00101, by a single missense mutation at CDS. PMID- 25131706 TI - Brain penetration of emodepside is increased in P-glycoprotein-deficient mice and leads to neurotoxicosis. AB - The antiparasitic drug emodepside (EMO) is a substrate of the P-glycoprotein multidrug efflux carrier (P-gp; syn. MDR1, ABCB1), which has an important function in protecting the brain from potentially toxic compounds by functional drug efflux at the blood-brain barrier (BBB). Many dogs of the Collie breed and even dogs of many other breeds have a loss-of-function 4-bp deletion mutation in the MDR1 gene. In these dogs, brain penetration of many P-gp-transported drugs is increased and so their therapeutic usage is restricted. To elucidate the role of P-gp at the BBB for the brain penetration of EMO, we applied EMO at 1 mg/kg to mdr1-deficient (PGP(mut) ) and mdr1-intact (PGP(WT) ) CF1 mice. Whereas in the brain of the PGP(WT) mice, EMO was below the detection level of 10 ng/g, its concentration was at 43.7 ng/g in the PGP(mut) mice. Furthermore, appearance of neurological toxicity was analyzed in these mice after application of 1 mg/kg EMO using a rotarod setup. In all PGP(mut) mice, but not in the PGP(WT) mice, the walking performance on the rotarod was impaired by EMO with clear differences in the degree and duration of neurological toxicity. Some of the mice were completely unable to walk on the rotarod already at 2 h after drug application and showed long-lasting ataxia over >24 h. Others even showed significantly reduced walking performance, but completely recovered within 1 day. In conclusion, P-gp restricts brain penetration of EMO and prevents neurological toxicity of this drug in mice. PMID- 25131707 TI - Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm. AB - BACKGROUND: Many studies have investigated the systemic and local expression of biomarkers in patients with abdominal aortic aneurysm (AAA). The natural history of AAA varies between patients, and predictors of the presence and diameter of AAA have not been determined consistently. The aim of this study was to perform a systematic review, meta-analysis and meta-regression of studies comparing biomarkers in patients with and without AAA, with the aim of summarizing the association of identified markers with both AAA presence and size. METHODS AND RESULTS: Literature review identified 106 studies suitable for inclusion. Meta analysis demonstrated a significant difference between matrix metalloproteinase (MMP) 9, tissue inhibitor of matrix metalloproteinase 1, interleukin (IL) 6, C reactive protein (CRP), alpha1-antitrypsin, triglycerides, lipoprotein(a), apolipoprotein A and high-density lipoprotein in patients with and without AAA. Although meta-analysis was not possible for MMP-2 in aortic tissue, tumour necrosis factor alpha, osteoprotegerin, osteopontin, interferon gamma, intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1, systematic review suggested an increase in these biomarkers in patients with AAA. Meta-regression analysis identified a significant positive linear correlation between aortic diameter and CRP level. CONCLUSION: A wide variety of biomarkers are dysregulated in patients with AAA, but their clinical value is yet to be established. Future research should focus on the most relevant biomarkers of AAA, and how they could be used clinically. PMID- 25131708 TI - Educational barriers of nurses caring for sick and at-risk infants in India. AB - AIM: To gain ideas and information from healthcare providers to optimize the education and clinical practices of nurses caring for sick or at-risk newborns in India. BACKGROUND: Improving infant survival has been identified as a Millennium Development Goals; however, India still faces many challenges with 3.1 million neonatal deaths and 2.6 million stillbirths annually. Skilled nursing care has been associated with decreased morbidity and mortality in newborns. However, core competencies in newborn care education and training are lacking for nurses. METHODS: Qualitative data were collected from 12 focus groups with 101 newborn care providers from three areas of India as well as from a 2-day stakeholders' meeting. Data analysis was undertaken using descriptive and thematic content analysis. RESULTS: Perceived challenges included limited manpower and high nurse turnover, lack of access to evidence-based orientation to newborn care and problems with access to appropriate learner-based, neonatal training. Relevant, ongoing education opportunities, led by nursing leaders were identified to be important solutions. CONCLUSION: Findings provide insight into the current healthcare system in India with specific reference to the nursing care of at-risk newborns. There is a lack of existing resources to provide standardized and specific orientation curricula for nurses. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Policy makers in health and education need to: support and enact learner based orientation and continuing educational opportunities as well as ongoing competency-based education programmes; encourage nurse leader involvement and support; and provide sustainable system-related supports. Nurses and other health providers need to work together to influence government policy. PMID- 25131709 TI - A descriptive qualitative study of the roles of family members in older men's depression treatment from the perspectives of older men and primary care providers. AB - OBJECTIVE: The aim of this study is to describe the roles of family members in older men's depression treatment from the perspectives of older men and primary care physicians (PCPs). METHODS: Cross-sectional, descriptive qualitative study conducted from 2008-2011 in primary care clinics in an academic medical center and a safety-net county teaching hospital in California's Central Valley. Participants in this study were the following: (1) 77 age >= 60, noninstitutionalized men with a 1-year history of clinical depression and/or depression treatment who were identified through screening in primary care clinics and (2) a convenience sample of 15 PCPs from the same recruitment sites. Semi-structured and in-depth qualitative interviews were conducted and audiotaped then transcribed and analyzed thematically. RESULTS: Treatment-promoting roles of family included providing an emotionally supportive home environment, promoting depression self-management and facilitating communication about depression during primary care visits. Treatment-impeding roles of family included triggering or worsening men's depression, hindering depression care during primary care visits, discouraging depression treatment and being unavailable to assist men with their depression care. Overall, more than 90% of the men and the PCPs described one or more treatment-promoting roles of family and over 75% of men and PCPs described one or more treatment-impeding roles of family. CONCLUSIONS: Families play important roles in older men's depression treatment with the potential to promote as well as impede care. Interventions and services need to carefully assess the ongoing roles and attitudes of family members and to tailor treatment approaches to build on the positive aspects and mitigate the negative aspects of family support. PMID- 25131711 TI - Jimmy Savile: the questions for bioethics. PMID- 25131710 TI - The proteasome inhibitor bortezomib reduced cholesterol accumulation in fibroblasts from Niemann-Pick type C patients carrying missense mutations. AB - Niemann-Pick disease type C (NPC) is a lipid storage disorder mainly caused by mutations in the NPC1 gene. Approximately 60% of these mutations are missense changes that may induce reduced NPC1 protein levels by increased degradation via ubiquitin-proteasome. This is the case for the most prevalent worldwide mutation, p.Ile1061Thr, as well as for other three missense changes. In the present study, we analyzed the NPC1 levels in fibroblasts from eighteen NPC patients presenting missense mutations. We found that fourteen of these cells lines showed decreased levels of NPC1. Six of these cell lines were homozygous, whereas the other eight were associated with a frame shifting mutation. We focused our attention in the NPC homozygous samples and demonstrated that, in most of the cases, NPC1 reduction was a consequence of a decrease of its half-life. NPC cells were treated not only with the proteasome inhibitors carbobenzoxy-l-leucyl-l-leucyl-l leucinal or N-acetyl-leucyl-leucyl-norleucinal, both widely used as a research tools, but also with bortezomib, the first proteasome inhibitor to reach clinical applications, although it has never been used in NPC disease. We observed that, after treatment, the mutant NPC1 protein levels were partially recovered in most of the cell lines. Importantly, these mutant proteins partially recovered their activity and substantially reduced free cholesterol levels. These results suggest that by enhancing the NPC1 protein stability with the use of proteasome inhibitors, their functionality might be recovered and this might represent a therapeutical approach for future treatments of NPC disease resulting from specific missense mutations. PMID- 25131712 TI - Withdrawal of skeletal muscle cells from cell cycle progression triggers differentiation of Toxoplasma gondii towards the bradyzoite stage. AB - Toxoplasma gondii is a widespread intracellular parasite of mammals and birds and an important opportunistic pathogen of humans. Following primary infection, fast replicating tachyzoites disseminate within the host and either are subsequently eliminated by the immune system or transform to latent bradyzoites which preferentially persist in brain and muscle tissues. The factors which determine the parasites' tissue distribution during chronic toxoplasmosis are unknown. Here we show that mouse skeletal muscle cells (SkMCs) after differentiation to mature, myosin heavy chain-positive, polynucleated myotubes, significantly restrict tachyzoite replication and facilitate expression of bradyzoite-specific antigens and tissue cyst formation. In contrast, proliferating mononuclear myoblasts and control fibroblasts enable vigorous T. gondii replication but do not sustain bradyzoite or tissue cyst formation. Bradyzoite formation correlates with upregulation of testis-specific Y-encoded-like protein-2 gene expression (Tspyl2) and p21(Waf1/Cip1 as well as downregulation of cyclin B1 and absence of DNA synthesis, i.e. a cell cycle arrest of syncytial myotubes. Following infection with T. gondii, myotubes but not myoblasts or fibroblasts further upregulate the negative cell cycle regulator Tspyl2. Importantly, RNA interference-mediated knock-down of Tspyl2 abrogates differentiation of SkMCs to myotubes and enables T. gondii to replicate vigorously but abolishes bradyzoite-specific gene expression and tissue cyst formation. Together, these data indicate that Tspyl2 mediated host cell cycle withdrawal is a physiological trigger of Toxoplasma stage conversion in mature SkMCs. This finding might explain the preferred distribution of T. gondii tissue cysts in vivo. PMID- 25131713 TI - Development of haemostatic decontaminants for the treatment of wounds contaminated with chemical warfare agents. 1: evaluation of in vitro clotting efficacy in the presence of certain contaminants. AB - The treatment of penetrating, haemorrhaging injuries sustained within a hazardous environment may be complicated by contamination with toxic chemicals. There are currently no specific medical countermeasures for such injuries. Haemostats with an absorbent mechanism of action have the potential to simultaneously stop bleeding and decontaminate wounds. However, a primary requirement of a 'haemostatic decontaminant' is the retention of clotting function in the presence of chemical contaminants. Thus, the aim of this study was to investigate the haemostatic efficacy of seven commercially available haemostats in the presence of toxic chemicals (soman, VX, sulphur mustard, petrol, aviation fuel and motor oil). Clot viscosity was assessed ex vivo using thrombelastography following treatment of pig blood with: (i) toxic chemical; (ii) haemostat; or (iii) haemostat in combination with toxic chemical. Several contaminants (VX, petrol and GD) were found to be pro-haemostatic and none had an adverse effect on the rate with which the test products attained haemostasis. However, the total clot strength for blood treated with certain haemostats in the presence of sulphur mustard, soman and petrol was significantly decreased. Three test products failed to demonstrate haemostatic function in this ex vivo (thrombelastography) model; this was tentatively ascribed to the products achieving haemostasis through a tamponade mechanism of action, which can only be replicated using in vivo models. Overall, this study has identified a number of commercial products that may have potential as haemostatic decontaminants and warrant further investigation to establish their decontaminant efficacy. PMID- 25131714 TI - What parents want to know about the storage and use of residual newborn bloodspots. AB - Many state newborn screening programs retain residual newborn screening bloodspots for a variety of purposes including quality assurance, biomedical research, and forensic applications. This project was designed to determine the information that prospective parents want to know about this practice. Eleven focus groups were conducted in four states. Pregnant women and their partners and parents of young children (N = 128) were recruited from the general public. Focus group participants viewed two educational movies on newborn screening and DBS retention and use. Transcripts were analyzed with qualitative methods and the results were synthesized to identify key information items. We identified 14 categories of information from the focus groups that were synthesized into seven items prospective parents want to know about residual DBS. The items included details about storage, potential uses, risks and burdens, safeguards, anonymity, return of results, and parental choice. For those state programs that retain residual dried bloodspots, inclusion of the seven things parents want to know about residual dried bloodspots in educational materials may improve parental understanding, trust, and acceptance of the retention and use of stored bloodspots. PMID- 25131715 TI - Deciding who should get live attenuated influenza vaccine. PMID- 25131716 TI - Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat. AB - BACKGROUND: Sex differences in cannabinoid effects have been reported in rodents, with adult females typically being more sensitive than adult males. The present study compared the development of antinociceptive tolerance to delta-9 tetrahydrocannabinol (THC) in adult, gonadally intact female vs. male rats. METHODS: Cumulative dose-effect curves were obtained for THC (1.0-18 mg/kg i.p.) on warm water tail withdrawal and paw pressure tests. Vehicle or the sex-specific ED80 dose for THC was administered twice daily for 9 days; THC dose-effect curves were then re-determined. RESULTS: On the pre-chronic test day, THC was significantly more potent in females than males in producing antinociception on the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC treatment (5.4 mg/kg/injection in females and 7.6 mg/kg/injection in males), THC potency on both tests decreased more in females than males. On the tail withdrawal test, chronic THC produced 4.2- vs. 2.8-fold increases in ED50 values in females vs. males, respectively. On the paw pressure test, chronic THC produced 4.4- vs. 2.9-fold increases in ED50 values in females vs. males, respectively. Chronic THC treatment did not significantly disrupt estrous cycling in females. CONCLUSIONS: These results demonstrate that--even when sex differences in acute THC potency are controlled--females develop more antinociceptive tolerance to THC than males. Given the importance of drug tolerance in the development of drug dependence, these results suggest that females may be more vulnerable than males to developing dependence after chronic cannabinoid exposure. PMID- 25131717 TI - Risky behavior and correlates of HIV and Hepatitis C Virus infection among people who inject drugs in three cities in Afghanistan. AB - BACKGROUND: Injecting drug use is the primary mode of HIV transmission and acquisition in Afghanistan. People who inject drugs (PWID) in the country have been characterized by high risk injecting behavior and a high burden of HCV infection. We aimed to estimate the burden of HIV, HCV, and other infectious diseases and to identify the correlates of HIV and HCV infection among PWID living in three major Afghan cities in 2009. METHODS: Epidemiologic data was collected among PWID for the integrated biological and behavioral surveillance (IBBS) survey between May and August, 2009 in three Afghan cities. Data were collected using a structured questionnaire and biologic specimens to screen for HIV, HBV, HCV, syphilis, and HSV-2 using rapid testing kits. Multiple logistic regression models were constructed to identify correlates of infection. RESULTS: Among 548 participants, pooled HIV prevalence was 7.1% (Mazar-i-Sharif: 1.0%, Kabul: 3.1%, Herat: 18.4%) and HCV prevalence was 40.3%. Almost all participants with HIV infection were co-infected with HCV (94.9%). Pooled prevalence estimates for other diseases included 7.1% for HBV, 5.5% for syphilis; and 9.3% for HSV-2. Living in Herat, ever in prison and time injecting were independently associated with HIV infection. Living in Kabul, Herat and time injecting were independently associated with HCV infection. CONCLUSIONS: There is a high and heterogeneous burden of HIV and HCV among PWID in Afghan cities. Provision of comprehensive harm reduction services to PWID in Afghanistan is warranted to reduce exposures associated with HIV and HCV infection, especially in the city of Herat. PMID- 25131718 TI - A microfabricated optofluidic ring resonator for sensitive, high-speed detection of volatile organic compounds. AB - Advances in microanalytical systems for multi-vapor determinations to date have been impeded by limitations associated with the microsensor technologies employed. Here we introduce a microfabricated optofluidic ring resonator (MUOFRR) sensor that addresses many of these limitations. The MUOFRR combines vapor sensing and fluidic transport functions in a monolithic microstructure comprising a hollow, vertical SiOx cylinder (250 MUm i.d., 1.2 MUm wall thickness; 85 MUm height) with a central quasi-toroidal mode-confinement section, grown and partially released from a Si substrate. The device also integrates on-chip fluidic-interconnection and fiber-optic probe alignment features. High-Q whispering gallery modes generated with a tunable 1550 nm laser exhibit rapid, reversible shifts in resonant wavelength arising from polymer swelling and refractive index changes as vapors partition into the ~300 nm PDMS film lining the cylinder. Steady-state sensor responses varied in proportion to concentration over a 50-fold range for the five organic vapors tested, providing calculated detection limits as low as 0.5 ppm (v/v) (for m-xylene and ethylbenzene). In dynamic exposure tests, responses to 5 MUL injected m-xylene vapor pulses were 710 ms wide and were only 18% broader than those from a reference flame ionization detector and also varied linearly with injected mass; 180 pg was measured and the calculated detection limit was 49 pg without use of preconcentration or split injection, at a flow rate compatible with efficient chromatographic separations. Coupling of this MUOFRR with a micromachined gas chromatographic separation column is demonstrated. PMID- 25131719 TI - Wind, water, wound, walk--do the data deliver the dictum? AB - OBJECTIVE: To evaluate the teaching dictum "wind, water, wound, walk" in the modern surgical environment. DESIGN: A retrospective cohort study. SETTING: Hospitals enrolled in the American College of Surgeons National Surgical Quality Improvement Program. PARTICIPANTS: We identified 11,137 patients enrolled in American College of Surgeons National Surgical Quality Improvement Program Participant Use File (2011) who were older than 18 years; underwent a general surgical procedure; and developed a postoperative pneumonia (PNA, "wind"), urinary tract infection (UTI, "water"), surgical site infection (SSI, "wound"), or venous thromboembolic event (VTE, "walk") for inclusion in the study. Patients were excluded if they had an infection present at the time of surgery or were missing information on the time of diagnosis. RESULTS: The median day of diagnosis differed significantly according to occurrence type (median day of PNA = 5, UTI = 8, SSI = 11, and VTE = 9, p < 0.001). The sequence of occurrences diagnosed before discharge (median day of PNA = 4, UTI = 5, SSI = 7, and VTE = 5) differed from that of occurrences diagnosed following discharge (median day of PNA = 10, UTI = 14, SSI = 14, and VTE = 14). Within the predischarge and postdischarge subsets, the median day of diagnosis remained significantly different according to occurrence type (all p's < 0.001). CONCLUSIONS: The dictum should be taught as, "wind, water, walk, wound" to reflect the timing and progression of the diagnosis of PNA, UTI, VTE, and SSI. The dictum did not reflect the timing or sequence of the occurrences in the cohort diagnosed after discharge. Educators must teach trainees to apply the dictum in the appropriate patient setting. As surgical care changes, we must continue to reassess our educational pearls to ensure that they reflect the modern reality. PMID- 25131721 TI - Impact of hepatitis C virus infection on the risk of death of alcohol-dependent patients. AB - Hepatitis C virus (HCV) infection is frequent among patients with alcohol use disorders. We aimed to analyse the impact of HCV infection on survival of patients seeking treatment for alcohol use. This was a longitudinal study in a cohort of patients who abused alcohol recruited in two detoxification units. Socio-demographic and alcohol use characteristics, liver function tests for the assessment of alcohol-related liver disease and HCV and HIV infection serologies were obtained at admission. Patients were followed until December 2008; causes of death were ascertained through clinical records and death registry. Cox models were used to analyse predictors of death. A total of 675 patients (79.7% men) were admitted; age at admission was 43.5 years (IQR: 37.9-50.2 years), duration of alcohol abuse was 18 years (IQR: 11-24 years), and median alcohol consumption was 200 g/day (IQR: 120-275 g/day). Distribution of patients according to viral infections was as follows: 75.7% without HCV or HIV infection, 14.7% HCV infection alone and 8.1% HCV/HIV coinfection. Median follow-up was 3.1 years (IQR: 1.5-5.1 years) accounting for 2,345 person-years. At the end of study, 78 patients (11.4%) had died. In the multivariate analysis, age at admission (HR = 1.71, 95%CI: 1.05-2.80), alcohol-related liver disease (HR = 3.55, 95%CI: 1.93 6.53) and HCV/HIV co-infection (HR = 3.86 95%CI: 2.10-7.11) were predictors of death. Younger patients (<=43 years) with HCV infection were more likely to die than those without viral infections (HR = 3.1, 95%CI: 1.3-7.3; P = 0.007). Among patients with alcohol-related liver disease, mortality rate was high, irrespective of viral infections. These data show that HCV infection confers a worse prognosis in patients with alcohol use disorders. PMID- 25131720 TI - The role of IL-28, IFN-gamma, and TNF-alpha in predicting response to pegylated interferon/ribavirin in chronic HCV patients. AB - The primary goal of HCV therapy is to achieve a sustained virological response (SVR). Many host and viral factors influence the treatment response. Cytokines play an important role in the defense against viral infections, where successful treatment of hepatitis C depends on a complex balance between pro- and anti inflammatory responses. In the present study, we investigated the relationship between the presence and percentage of some cytokines (IL-28, IFN-gamma, and TNF alpha) regarding different clinicopathological parameters including response to therapy in chronic HCV patients using immunohistochemical technique. This study was carried out on 64 chronic HCV patients (34 responders and 30 non-responders). Of cases, 54% showed IL-28 expression, which was associated with low AST (p = 0.002) and low HAI score (p = 0.006). Of cases, 67 and 45% showed IFN-gamma and TNF-alpha expression, respectively, where the median percentage of TNF-alpha expression was higher in grade II spotty necrosis compared to grade I. Some inflammatory cytokines expressed by intrahepatic inflammatory cells in chronic HCV patients promote inflammation and injury (pro-inflammatory) such as TNF alpha. Other cytokines aid in resolving inflammation and injury (anti inflammatory) such as IL-28. The balance between these cytokines will determine the degree of inflammatory state. None of the investigated cytokines proved its clear cut role in affecting response to therapy, however, their levels varied between responders and non-responders for further investigations to clarify. PMID- 25131722 TI - Quantifying histone and RNA polymerase II post-translational modification dynamics in mother and daughter cells. AB - Post-translational histone modifications are highly correlated with transcriptional activity, but the relative timing of these marks and their dynamic interplay during gene regulation remains controversial. To shed light on this problem and clarify the connections between histone modifications and transcription, we demonstrate how FabLEM (Fab-based Live Endogenous Modification labeling) can be used to simultaneously track histone H3 Lysine 9 acetylation (H3K9ac) together with RNA polymerase II Serine 2 and Serine 5 phosphorylation (RNAP2 Ser2ph/Ser5ph) in single living cells and their progeny. We provide a detailed description of the FabLEM methodology, including helpful tips for preparing and loading fluorescently conjugated antigen binding fragments (Fab) into cells for optimal results. We also introduce simple procedures for analyzing and visualizing FabLEM data, including color-coded scatterplots to track correlations between modifications through the cell cycle and temporal cross correlation analysis to dissect modification dynamics. Using these methods, we find significant correlations that span cell generations, with a relatively strong correlation between H3K9ac and Ser5ph that appears to peak a few hours before mitosis and may reflect the bookmarking of genes for efficient re initiation following mitosis. The techniques we have developed are broadly applicable and should help clarify how histone modifications dynamically contribute to gene regulation. PMID- 25131723 TI - Moonlighting proteins as virulence factors of pathogenic fungi, parasitic protozoa and multicellular parasites. AB - The delicate balance between eukaryotic pathogens and their human hosts during the initiation and development of infection is a complex process involving many diverse interactions. Different infectious agents, including pathogenic fungi, parasitic protozoa and multicellular parasites, directly interact through their cell surface with epithelial or endothelial cells of the human host as well as various proteinaceous host ligands such as extracellular matrix or plasma proteins. Eukaryotic pathogens possess a number of virulence factors but a relatively recently recognized and particularly interesting group of factors capable of enhancing virulence is the set of so-called 'moonlighting proteins'. This term was coined for a relatively large collection of housekeeping enzymes lacking special targeting motifs that would determine their extracellular localization, but that are often present at the cell surface of pathogen. Several such enzymes with key metabolic functions in glycolysis, the pentose phosphate cycle or other fundamental intracellular processes perform entirely new, non catalytic roles often associated with adhesion to host ligands. Our current study summarizes some of the current knowledge of interesting moonlighting proteins which play putative or confirmed roles as virulence factors in pathogenic fungi, parasitic protozoa and multicellular parasites. PMID- 25131724 TI - Quantification and genotyping of lipoprotein lipase in patients with diabetic lipaemia. AB - AIMS: To determine if diabetic lipaemia is caused by loss of function mutations in the lipoprotein lipase gene, LPL. METHODS: We conducted a case-control study over 2 years in two tertiary care hospitals in South Australia. Six patients with a history of diabetic lipaemia and 12 control subjects, with previous diabetic ketoacidosis and peak triglyceride concentrations < 2.4 mmol/l were included. Participants were well at the time of study investigations. RESULTS: Only one patient with lipaemia had a loss of function mutation in LPL and no functional mutations in APOC2 or GPIHBP1 were identified. The mean lipoprotein lipase concentration was lower in patients with diabetic lipaemia than in control subjects (306 vs. 484 MUg/l, P = 0.04). The mean fasting C-peptide concentration was higher in patients with diabetic lipaemia than in control subjects (771 vs. 50 pmol/l; P = 0.001). CONCLUSIONS: Lipoprotein lipase deficiency in patients with a history of diabetic lipaemia was predominantly quantitative, rather than secondary to mutations in LPL, APOC2 or GPIHBP1. The majority of patients with severe hypertriglyceridaemia in diabetic ketoacidosis may have ketosis-prone Type 2, rather than Type 1, diabetes. PMID- 25131725 TI - A novel CYLD germline mutation in Brooke-Spiegler syndrome. AB - BACKGROUND: Brooke-Spiegler syndrome (BSS) is a rare, inherited, autosomal dominant disorder characterized by the development of multiple adnexal neoplasms including spiradenomas, cylindromas, trichoepitheliomas and major and minor salivary glands neoplasms. This syndrome encompasses a wide variability of clinical phenotypes depending on the variable number of tumours present in the given patient. OBJECTIVE: Somatic mutations in adjunct to CYLD germline mutations may play a central role in the development of the tumour phenotype and in the genotype-phenotype correlations. METHODS: Blood sample and paraffin embedded tissue biopsied from three cylindromas, one trichoepithelioma and one spiradenomas were collected after obtaining informed consent from our patient and genomic DNA was isolated. RESULTS: We found out a novel germline mutation in the CYLD gene in exon 15 that resulted in the deletion of one nucleotide. This gives rise to a premature translational termination codon at amino acid position 693 prior to four Cys-X-X-Cys pairs and one of the two catalytic domains of ubiquitin carboxy-terminal hydrolases. In only one cylindroma we detected the same germline mutation (c.2070delT/p.F690FfsX3) in addition to two somatic events (I645V and R936X). The presence of this unique mutation could be linked to the peculiar phenotype of our patient who presented an attenuated form of BSS, an autosomal dominant inheritance with low penetrance and no additional visceral tumours. CONCLUSIONS: The overall phenotype of our patient may support the hypothesis that somatic mutations in adjunct to CYLD germline mutations may play a central role in the development of the tumour phenotype and in the genotype-phenotype correlations. PMID- 25131727 TI - Technology transfer and scale-up of the Flublok recombinant hemagglutinin (HA) influenza vaccine manufacturing process. AB - Multiple different hemagglutinin (HA) protein antigens have been reproducibly manufactured at the 650L scale by Protein Sciences Corporation (PSC) based on an insect cell culture with baculovirus infection. Significantly, these HA protein antigens were produced by the same Universal Manufacturing process as described in the biological license application (BLA) for the first recombinant influenza vaccine approved by the FDA (Flublok). The technology is uniquely designed so that a change in vaccine composition can be readily accommodated from one HA protein antigen to another one. Here we present a vaccine candidate to combat the recently emerged H7N9 virus as an example starting with the genetic sequence for the required HA, creation of the baculovirus and ending with purified protein antigen (or vaccine component) at the 10L scale accomplished within 38 days under GMP conditions. The same process performance is being achieved at the 2L, 10L, 100L, 650L and 2500L scale. An illustration is given of how the technology was transferred from the benchmark 650L scale facility to a retrofitted microbial facility at the 2500L scale within 100 days which includes the time for facility engineering changes. The successful development, technology transfer and scale-up of the Flublok process has major implications for being ready to make vaccine rapidly on a worldwide scale as a defense against pandemic influenza. The technology described does not have the same vulnerability to mutations in the egg adapted strain, and resulting loss in vaccine efficacy, faced by egg based manufacture. PMID- 25131726 TI - Assessing the feasibility of hepatitis C virus vaccine trials: results from the Hepatitis C Incidence and Transmission Study-community (HITS-c) vaccine preparedness study. AB - Efficacy trials of preventive hepatitis C virus (HCV) vaccine candidates raise challenging scientific and ethical issues. Based on data from the first 3 years of a community-based prospective observational study - the Hepatitis C Incidence and Transmission Study-community (HITS-c) - this paper examines the feasibility of conducting trials of candidate HCV vaccines with people who inject drugs (PWID) in Sydney, Australia. Of the 166 PWID confirmed HCV antibody negative and eligible for enrolment, 156 (94%) completed baseline procedures. Retention was high, with 89% of participants retained at 48 weeks and 76% of participants completing at least 75% of study visits within 2 weeks of schedule. The rate of primary HCV infection was 7.9/100 py (95% CI 4.9, 12.7). Of the 17 incident cases, 16 completed at least one follow-up assessment and 12 (75%) had evidence of chronic viraemia with progression to chronic HCV infection estimated to be 6/100 py. Power calculations suggest a chronic HCV infection rate of at least 12/100 py (primary HCV infection rate 16/100 py) will be required for stand-alone trials of highly efficacious candidates designed to prevent chronic infection. However, elevated primary HCV infection was observed among participants not receiving opioid substitution therapy who reported heroin as the main drug injected (26.9/100 py, 95% CI 14.5, 50.0) and those who reported unstable housing (23.5/100 py, 95% CI 7.6, 72.8), daily or more frequent injecting (22.7/100 py, 95% CI 12.2, 42.2) and receptive syringe sharing (23.6/100 py, 95% CI 9.8, 56.7) in the 6 months prior to baseline. These data suggest that it is possible to recruit and retain at-risk PWID who adhere to study protocols and that modification of eligibility criteria may identify populations with sufficiently high HCV incidence. Results support the feasibility of large multi-centre HCV vaccine trials, including in the Australian setting. PMID- 25131728 TI - Characterization and immunogenicity in mice of recombinant influenza haemagglutinins produced in Leishmania tarentolae. AB - The membrane displayed antigen haemagglutinin (HA) from several influenza strains were expressed in the Leishmania tarentolae system. This non-conventional expression system based on a parasite of lizards, can be readily propagated to high cell density (>10(8)cells/mL) in a simple incubator at 26 degrees C. The genes encoding HA proteins were cloned from six influenza strains, among these being a 2009 A/H1N1 pandemic strain from swine origin, namely A/California/07/09(H1N1). Soluble HA proteins were secreted into the cell culture medium and were easily and successfully purified via a His-Tag domain fused to the proteins. The overall process could be conducted in less than 3 months and resulted in a yield of approximately 1.5-5mg of HA per liter of biofermenter culture after purification. The recombinant HA proteins expressed by L. tarentolae were characterized by dynamic light scattering and were observed to be mostly monomeric. The L. tarentolae recombinant HA proteins were immunogenic in mice at a dose of 10MUg when administered twice with an oil-in-water emulsion based adjuvant. These results suggest that the L. tarentolae expression system may be an alternative to the current egg-based vaccine production. PMID- 25131729 TI - Effect of multiple, simultaneous vaccines on polio seroresponse and associated health outcomes. AB - BACKGROUND: Administration of multiple simultaneous vaccines to infants, children, and military recruits is not uncommon. However, little research exists to examine associated serological and health effects, especially in adults. METHOD: We retrospectively examined 416 paired serum specimens from U.S. military subjects who had received the inactivated polio vaccine (IPV) alone or in combination with either 1 other vaccine (<3 group) or 4 other vaccines (>4 group). Each of the 2 groups was subdivided into 2 subgroups in which Tdap was present or absent. RESULTS: The >4 group was associated with a higher proportion of polio seroconversions than the <3 group (95% vs. 58%, respectively, p<0.01). Analysis of the <3 subgroup that excluded Tdap vs. the >4 subgroup that excluded Tdap showed no difference between them (p>0.1). However, the >4 subgroup that included Tdap had significantly more seroconversions than either the <3 subgroup that excluded Tdap or the >4 subgroup that excluded Tdap (p<0.01). Overall, at least 98% of subjects were at or above the putative level of seroprotection both pre- and post-vaccination, yet at least 81% of subjects seroconverted. In an analysis of 400 of the subjects in which clinic in- and outpatient encounters were counted over the course of 1 year following vaccinations, there was no significant difference between the 2 groups (p>0.1). CONCLUSION: A combination of >4 vaccines including IPV appeared to have an immunopotentiation effect on polio seroconversion, and Tdap in particular was a strong candidate for an important role. The dose of IPV we studied in our subjects, who already had a high level of seroprotection, acted as a booster. In addition, there appear to be no negative health consequences from receiving few versus more multiple simultaneous vaccinations. PMID- 25131730 TI - TLR7/8 agonists activate a mild immune response in rabbits through TLR8 but not TLR7. AB - Toll-like receptors 7 (TLR7) and 8 (TLR8) recognize viral single-stranded RNA and small molecular weight agonists to activate anti-viral immune responses. TLR8s from different species have distinct ligand recognitions. For example, human TLR8 is responsive to ligand stimulation, but mouse and rat TLR8 are activated by small molecular weight agonists only in the presence of polyT oligodeoxynucleotides. TLR7 and TLR8 have been reported to be absent and pseudogenized, respectively, in rabbit (Oryctolagus cuniculus). In this study, we detected the expression of rabbit (rab)TLR8 in immune-cell-associated tissues. Cell proliferation and cytokine expressions in rabbit splenocytes were induced by the TLR7/8 ligand but not by the TLR7 ligands, suggesting that rabTLR8 is functional but rabTLR7 is not. In rabbits, CL075, a TLR7/8 ligand, activated an antigen-specific antibody response, although one not as potent as aluminum salt or Freund's adjuvant. Nevertheless, CL075, alone or in combination with aluminum salt, generates fewer adverse effects than Freund's adjuvant at the injection sites. To further investigate the activation of rabTLR8, we cloned its cDNA. In cell-based assay, this rabTLR8 is activated by TLR7/8 ligand but not activated by TLR7 ligand. Upon stimulation the rabTLR8 had a lower activation compared to the activation of TLR8 from other species, except the mouse and rat TLR8s. Using different deletion and human-rabbit chimeric TLR8 expressing constructs, we showed that an extra peptide in the undefined region results in reduced activity of rabTLR8. These results provide a molecular basis for the mild activities of TLR7/8 ligands in rabbits, and suggest TLR7/8 agonists may provide safer immune stimuli in rabbits than in other non-rodent species. PMID- 25131731 TI - Activation of dendritic cell function by soypeptide lunasin as a novel vaccine adjuvant. AB - The addition of an appropriate adjuvant that activates the innate immunity is essential to subsequent development of the adaptive immunity specific to the vaccine antigens. Thus, any innovation capable of improving the immune responses may lead to a more efficacious vaccine. We recently identified a novel immune modulator using a naturally occurring seed peptide called lunasin. Lunasin was originally isolated from soybeans, and it is a small peptide containing 43 amino acids. Our studies revealed stimulatory effects of lunasin on innate immune cells by regulating expression of a number of genes that are important for immune responses. The objective was to define the effectiveness of lunasin as an adjuvant that enhances immune responses. The immune modulating functions of lunasin were characterized in dendritic cells (DCs) from human peripheral blood mononuclear cells (PBMCs). Lunasin-treated conventional DCs (cDCs) not only expressed elevated levels of co-stimulatory molecules (CD86, CD40) but also exhibited up-regulation of cytokines (IL1B, IL6) and chemokines (CCL3, CCL4). Lunasin-treated cDCs induced higher proliferation of allogeneic CD4+ T cells when comparing with medium control treatment in the mixed leukocyte reaction (MLR). Immunization of mice with ovalbumin (OVA) and lunasin inhibited the growth of OVA expressing A20 B-lymphomas, which was correlated with OVA-specific CD8+ T cells. In addition, lunasin was an effective adjuvant for immunization with OVA, which together improved animal survival against lethal challenge with influenza virus expressing the MHC class I OVA peptide SIINFEKL (PR8-OTI). These results suggest that lunasin may function as a vaccine adjuvant by promoting DC maturation, which in turn enhances the development of protective immune responses to the vaccine antigens. PMID- 25131732 TI - Economic evaluation of meningococcal serogroup B childhood vaccination in Ontario, Canada. AB - OBJECTIVE: Invasive Neisseria meningitidis serogroup B (MenB) disease is a low incidence but severe infection (mean annual incidence 0.19/100,000/year, case fatality 11%, major long-term sequelae 10%) in Ontario, Canada. This study assesses the cost-effectiveness of a novel MenB vaccine from the Ontario healthcare payer perspective. METHODS: A Markov cohort model of invasive MenB disease based on high quality local data and data from the literature was developed. A 4-dose vaccination schedule, 97% coverage, 90% effectiveness, 66% strain coverage, 10-year duration of protection, and vaccine cost of C$75/dose were assumed. A hypothetical Ontario birth cohort (n=150,000) was simulated to estimate expected lifetime health outcomes, quality-adjusted life years (QALYs), and costs, discounted at 5%. RESULTS: A MenB infant vaccination program is expected to prevent 4.6 invasive MenB disease cases over the lifetime of an Ontario birth cohort, equivalent to 10 QALYs gained. The estimated program cost of C$46.6 million per cohort (including C$318,383 for treatment of vaccine associated adverse events) were not offset by healthcare cost savings of C$150,522 from preventing MenB cases, resulting in an incremental cost of C$4.76 million per QALY gained. Sensitivity analyses showed the findings to be robust. CONCLUSIONS: An infant MenB vaccination program significantly exceeds commonly used cost-effectiveness thresholds and thus is unlikely to be considered economically attractive in Ontario and comparable jurisdictions. PMID- 25131733 TI - The muscle findings in a pediatric patient with live attenuated oral polio vaccine-related flaccid monoplegia. AB - A pediatric patient, who was given live-attenuated oral polio vaccine twice without distinct gait disturbance during infancy, begun to present limp at 3 years. His gait disturbance became remarkable with aging. At 7 years, he was unable to dorsiflex the left ankle, and presented flaccid monoplegia of the left lower extremity, and the left Achilles tendon reflex was diminished. Magnetic resonance imaging revealed multiple crack-lines in the left anterior tibial muscle, but was unable to detect any distinct lesion at responsible level of L4, L5 and S1 anterior horn cells' degeneration. Electromyography showed continuous fibrillation potentials, but muscle biopsy presented nearly normal in this muscle. The serum levels of polio antibody type 1 and type 2 titers were elevated 64* respectively, while the type 3 antibody titer was not elevated 4*. This patient was diagnosed as live attenuated oral polio vaccine-related flaccid monoplegia, with mild clinical course. PMID- 25131734 TI - Reactogenicity and immunogenicity of inactivated poliovirus vaccine produced from Sabin strains: a phase I Trial in healthy adults in Cuba. AB - BACKGROUND: To ensure that developing countries have the option to produce inactivated poliovirus vaccine (IPV), the Global Polio Eradication Initiative has promoted the development of an IPV using Sabin poliovirus strains (Sabin IPV). This trial assessed the reactogenicity and immunogenicity of Sabin IPV and adjuvanted Sabin IPV in healthy adults in Cuba. METHODS: This is a randomized, controlled phase I trial, enrolling 60 healthy (previously vaccinated) male human volunteers, aged 19-23 years to receive one dose of either Sabin IPV (20:32:64 DU/dose), adjuvanted Sabin IPV (10:16:32 DU/dose), or conventional Salk IPV (40:8:32 DU/dose). The primary endpoint for reactogenicity relied on monitoring of adverse events. The secondary endpoint measured boosting immune responses (i.e. seroconversion or 4-fold rise) of poliovirus antibody, assessed by neutralization assays. RESULTS: Sixty subjects fulfilled the study requirements. No serious adverse events reported were attributed to trial interventions during the 6-month follow-up period. Twenty-eight days after vaccination, boosting immune responses against poliovirus types 1-3 were between 90% and 100% in all vaccination groups. There was a more than 6-fold increase in median antibody titers between pre- and post-vaccination titers in all vaccination groups. DISCUSSION: Both Sabin IPV and adjuvanted Sabin IPV were well tolerated and immunogenic against all poliovirus serotypes. This result suggests that the aluminum adjuvant may allow a 50% (or higher) dose reduction. PMID- 25131736 TI - Natural killer cell responses to dendritic cells infected by the ANRS HIV-1 vaccine candidate, MVAHIV. AB - Innate mechanisms are critical for the development of the host immune responses to antigen. Particularly, early interaction between natural killer (NK) cells and dendritic cells (DC) greatly impacts the establishment of both innate and adaptive immune responses. In this study, using an autologous in vitro co-culture system we analyzed the NK cell response against MVAHIV-infected DC as well as the subsequent ability of these MVAHIV-primed NK cells to control HIV-1 infection in autologous DC. We found that NK cells responded early to MVAHIV- or MVAWT infected DC in terms of degranulation and cytokine production. After a 4-day priming of NK cells by MVAHIV- or MVAWT-infected DC we observed an enhanced proliferation and modulation in the NK cell receptor repertoire expression. Interestingly, we found that MVAHIV-primed NK cells had a significant higher ability to control HIV-1 infection in autologous DC compared to MVAWT-primed NK cells; and this enhanced anti-HIV-1 activity appeared to be HIV-specific as MVAHIV-primed NK cells did not have a better ability to control other viral infections or respond against tumoral cells. Furthermore, we observed that NK cell receptors NKG2D and NKp46 modulate the priming of NK cells. This data provides evidence that in vitro NK cells can be primed by viral vector-infected DC, in the context of a NK/DC culture, to specifically target viral infected cells. PMID- 25131737 TI - Intradermal and virosomal influenza vaccines for preventing influenza hospitalization in the elderly during the 2011-2012 influenza season: a comparative effectiveness study using the Valencia health care information system. AB - BACKGROUND: The use of intradermal vaccination or virosomal vaccines could increase protection against influenza among the vulnerable population of older adults. Studies assessing the comparative effectiveness of these two influenza vaccine types in this age group are lacking. METHODS: We conducted a retrospective cohort study to estimate the comparative effectiveness of intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle injection system and a virosomal-TIV intramuscularly delivered for prevention of influenza hospitalization in non-institutionalized adults aged >=65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2011-2012 influenza season, and used Cox regression models to assess comparative effectiveness. We estimated crude and adjusted (age, sex, comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of hospitalizations for all causes other than influenza between the previous and current influenza seasons) hazard ratios (HR). RESULTS: Overall, 164,021 vaccinated subjects were evaluated. There were 127 hospitalizations for influenza among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal TIV group, and 133 hospitalizations for influenza among 101,963 subjects, contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence interval (CI): 0.50-0.81), and the adjusted Cox estimated HR was 0.67 (95% CI: 0.52-0.85). CONCLUSIONS: During the 2011-2012 influenza season the risk of hospitalization for influenza was reduced by 33% in non-institutionalized elderly adults who were vaccinated with intradermal-TIV compared with virosomal-TIV. PMID- 25131738 TI - Chronic helminth infections impair pneumococcal vaccine responses. AB - Pneumonia is the leading killer of children and disproportionately affects developing countries. Vaccination campaigns against Streptococcus pneumoniae, the leading cause of pneumonia, have recently been launched with a new conjugate vaccine in Africa. Using a mouse model, we assessed the potential role that the high burden of helminth infections in the countries targeted for vaccine might have on vaccine effectiveness. Mice vaccinated with either commercial conjugate or purified polysaccharide vaccines had impaired antibody responses if they were chronically infected with Taenia crassiceps. This translated to increased susceptibility to pneumococcal pneumonia and high mortality compared to helminth negative vaccinated animals, which were fully protected from disease and death. Antibodies taken from Taenia-infected, vaccinated mice were unable to effectively opsonize S. pneumoniae for killing by alveolar macrophages, and did not protect against pneumococcal challenge when adoptively transferred into naive animals. These data may have implications for vaccination programs in countries endemic with helminths. PMID- 25131735 TI - Interaction between neonatal vitamin A supplementation and timing of measles vaccination: a retrospective analysis of three randomized trials from Guinea Bissau. AB - BACKGROUND: In Guinea-Bissau we conducted three trials of neonatal vitamin A supplementation (NVAS) from 2002 to 2008. None of the trials found a beneficial effect on mortality. From 2003 to 2007, an early measles vaccine (MV) trial was ongoing, randomizing children 1:2 to early MV at 4.5 months or no early MV, in addition to the usual MV at 9 months. We have previously found interactions between vitamin A and vaccines. OBJECTIVE: We investigated whether there were interactions between NVAS and early MV. DESIGN: We compared the mortality of NVAS and placebo recipients: first, from 4.5 to 8 months for children randomized to early MV or no early MV; and second, from 9 to 17 months in children who had received two MV or one MV. Mortality rates (MR) were compared in Cox models producing mortality rate ratios (MRR). RESULTS: A total of 5141 children were randomized to NVAS (N=3015) or placebo (N=2126) and were later randomized to early MV (N=1700) or no early MV (N=3441). Between 4.5 and 8 months, NVAS compared with placebo was associated with higher mortality in early MV recipients (MR=30 versus MR=0, p=0.01), but not in children who did not receive early MV (p for interaction between NVAS and early MV=0.03). From 9 to 17 months NVAS was not associated with mortality. Overall, from 4.5 to 17 months NVAS was associated with increased mortality in early MV recipients (Mortality rate ratio=5.39 (95% confidence interval: 1.62, 17.99)). CONCLUSIONS: These observations indicate that NVAS may interact with vaccines given several months later. This may have implications for the planning of future child intervention programs. PMID- 25131739 TI - Utilization of administrative data to assess the association of an adolescent health check-up with human papillomavirus vaccine uptake in Germany. AB - BACKGROUND: In Germany, 3-dose human papillomavirus (HPV) vaccination is recommended for 12-17 year-old females. Countrywide monitoring of HPV vaccination coverage (VC) does not exist, but small-scale surveys suggested suboptimal uptake. There is currently no concerted implementation strategy in place, and approaches for improved vaccine delivery are needed. Our objectives were to analyze health insurance claims data to estimate HPV VC in the target population and to assess the association of the routine adolescent health check-up 'J1' (offered to 12-14 year-olds) with HPV vaccine uptake. METHODS: We sampled a subset of 12-16 year-old females from claims data in 15 of the 16 German federal states. Sampling was based on documented physician contacts flanking the follow up period 2008-2012. We reconstructed age- and region-stratified histories of individual-level HPV vaccination series and J1 utilization and calculated country level estimates. RESULTS: The study sample represented 54% (n=1.04 million) of the total target population. VC estimates for starting (and completing) HPV vaccination series ranged from 6.1% (1.2%) among 12-year-olds to 47.6% (36.2%) among 16-year-olds. J1 utilization was 50% at maximum. In J1-attendees, 42.0% had received >=1 vaccine doses, translating into a significant association of J1 utilization and vaccine uptake with a 6.9-fold higher likelihood in 12-year-olds and 1.4-fold higher likelihood in 16-year-olds of receiving HPV vaccination. CONCLUSION: HPV VC in Germany is low. Adolescent check-up J1 is associated with increased and accelerated HPV vaccine uptake securing immunization before sexual debut and should be used as a tool to improve VC in the target population. However, J1 utilization is only moderate and more than half of attendees had not received HPV vaccination, which represents a substantial proportion of missed opportunities. This indicates that J1 needs both further promotion through legislative structures already in place for other health check-ups and more awareness as an opportunity to offer HPV vaccinations. PMID- 25131740 TI - Studies on recombinant glucokinase (r-glk) protein of Brucella abortus as a candidate vaccine molecule for brucellosis. AB - Brucellosis is one of the most prevalent zoonotic diseases of worldwide distribution caused by the infection of genus Brucella. Live attenuated vaccines such as B. abortus S19, B. abortus RB51 and B. melitensis Rev1 are found most effective against brucellosis infection in animals, contriving a number of serious side effects and having chances to revert back into their active pathogenic form. In order to engineer a safe and effective vaccine candidate to be used in both animals and human, a recombinant subunit vaccine molecule comprising the truncated region of glucokinase (r-glk) gene from B. abortus S19 was cloned and expressed in Escherichia coli BL21DE3 host. Female BALB/c mice immunized with purified recombinant protein developed specific antibody titer of 1:64,000. The predominant IgG2a and IgG2b isotypes signified development of Th1 directed immune responses. In vitro cell cytotoxicity assay using anti-r-glk antibodies incubated with HeLa cells showed 81.20% and 78.5% cell viability against lethal challenge of B. abortus 544 and B. melitensis 16M, respectively. The lymphocyte proliferative assay indicated a higher splenic lymphocyte responses at 25MUg/ml concentration of protein which implies the elevated development of memory immune responses. In contrast to control, the immunized group of mice intra-peritoneal (I.P.) challenged with B. abortus 544 were significantly protected with no signs of necrosis and vacuolization in their liver and spleen tissue. The elevated B-cell response associated with Th1 adopted immunity, significant in vitro cell viability as well as protection afforded in experimental animals after challenge, supplemented with histopathological analysis are suggestive of r-glk protein as a prospective candidate vaccine molecule against brucellosis. PMID- 25131741 TI - The incidence of pediatric invasive Haemophilus influenzae and pneumococcal disease in Chiba prefecture, Japan before and after the introduction of conjugate vaccines. AB - The Haemophilus influenzae type b (Hib) vaccine and the heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in 2008 and 2010, respectively. In 2011, immunization with these two vaccines was encouraged throughout Japan through a governmental program. Children treated in Chiba prefecture for culture proven invasive H. influenzae disease (IHiD) and invasive Streptococcus pneumoniae disease (IPD) were identified in a prefectural surveillance study from 2008 to 2013. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare the 3 years before and after governmental financial support for vaccination. The average number of IHiD and IPD cases among children <5 years of age in 2011-2013 decreased 84% (IRR: 0.16, 95% CI: 0.09-0.26, p<0.0001) and 51% (IRR: 0.49, 95% CI: 0.37-0.63, p<0.0001) compared with those occurring in 2008-2010. The most common non-PCV7 serotype encountered in 2011 and 2013 was 19A. After governmental subsidization of Hib and PCV7 vaccination, IHiD and IPD decreased in Chiba prefecture, Japan. Continuous surveillance is necessary to determine the effectiveness of these two vaccines and for detection of emerging invasive serotypes. PMID- 25131742 TI - Influenza vaccination in HIV-infected individuals: systematic review and assessment of quality of evidence related to vaccine efficacy, effectiveness and safety. AB - BACKGROUND: Influenza infection in HIV-infected individuals is associated with increased severity of illness. We performed a systematic review of the available evidence on efficacy, effectiveness and safety of seasonal influenza vaccination in HIV-infected individuals. DESIGN: Systematic review, meta-analysis and assessment of evidence quality. METHODS: Using a previous systematic review as starting point, we searched MEDLINE, EMBASE and Cochrane data base for studies on efficacy, effectiveness or safety of trivalent inactivated influenza vaccines (TIV) in HIV-infected individuals. Evidence quality was assessed for each outcome using the GRADE methodology. RESULTS: Three randomized-controlled trials and three cohort studies were identified, including a total of 1562 HIV-infected individuals. In adults, TIV prevented laboratory-confirmed influenza with a pooled efficacy of 85% (95% CI, 22-97%) (evidence quality: moderate), but no significant effects on other clinical outcomes were observed (evidence quality: moderate to low). One cohort study showed an effectiveness of 71% (95% CI, 44 85%) for prevention of laboratory-confirmed influenza, whereas no effect on influenza-like illness was found. However, risk of bias was high in all observational studies. In children aged 6-59 months, efficacy of TIV in preventing laboratory-confirmed influenza was 11% (95% CI, -30 to 54%) (evidence quality: moderate). Regarding other endpoints, no statistically significant effects were reported (evidence quality: moderate to low). No severe adverse events following influenza vaccination were observed in these studies. CONCLUSION: This systematic review indicates that TIV is effective in preventing influenza infection in HIV-infected adults but not in young children. For both age-groups, only limited evidence exists for other outcomes, indicating a need for further studies. PMID- 25131743 TI - Comparing the cost-effectiveness of two- and three-dose schedules of human papillomavirus vaccination: a transmission-dynamic modelling study. AB - BACKGROUND: Recent evidence suggests that two doses of HPV vaccines may be as protective as three doses in the short-term. We estimated the incremental cost effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV vaccination programmes in Canada. METHODS: We used HPV-ADVISE, an individual based transmission-dynamic model of multi-type HPV infection and diseases (anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and oropharynx). We conducted the analysis from the health payer perspective, with a 70-year time horizon and 3% discount rate, and performed extensive sensitivity analyses, including duration of vaccine protection and vaccine cost. FINDINGS: Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY) gained varying between $7900-24,300. The incremental cost-effectiveness ratio of giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained when: (i) three doses provide longer protection than two doses and (ii) two-dose protection was shorter than 30 years. Vaccinating boys (with two or three doses) was not cost-effective (vs. girls-only vaccination) under most scenarios investigated. INTERPRETATION: Two-dose HPV vaccination is likely to be cost effective if its duration of protection is at least 10 years. A third dose of HPV vaccine is unlikely to be cost-effective if two-dose duration of protection is longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely to be cost-effective unless the cost per dose for boys is substantially lower than the cost for girls. PMID- 25131744 TI - Primary care providers human papillomavirus vaccine recommendations for the medically underserved: a pilot study in U.S. Federally Qualified Health Centers. AB - INTRODUCTION: In the United States, Federally Qualified Health Centers (FQHCs) are safety-net clinics that provide cervical cancer screening and human papillomavirus (HPV) vaccination to medically underserved women, some of whom may be at risk for developing cervical cancer. National guidelines recommend against using screening test results or sexual history to determine vaccine eligibility. Documenting HPV vaccine recommendations and beliefs of primary care providers in FQHCs may aid in promoting evidence-based practices and prioritizing health interventions for vulnerable populations. METHODS: Between 2009 and 2010, we collected data from 98 primary care providers in 15 FQHC clinics in IL, USA using a cross-sectional survey. Questions assessed provider and practice characteristics, HPV vaccine recommendations, and provider's belief about whether their screening and management procedures would change for women who were vaccinated. RESULTS: 93% of providers recommended the HPV vaccine, most frequently for females aged 13-26 years (98%). Some providers reported sometimes to always using HPV test results (12%), Pap test results (7%), and number of sexual partners (33%) to determine vaccine eligibility. More than half of providers (55%) reported they will not change their screening and management practices for vaccinated females, yet believe vaccination will yield fewer abnormal Pap tests (71%) and referrals for colposcopy (74%). CONCLUSION: Study providers routinely recommended the HPV vaccine for their patients. However, providers made fewer recommendations to vaccinate females ages 9-12 years (which includes the target age for vaccination) compared to older females, and used pre vaccination assessments not recommended by U.S. guidelines, such as screening test results and number of sexual partners. In order to maximize the public health benefit of the HPV vaccine to prevent cervical cancer, adherence to guidelines is necessary, especially in settings that provide care to medically underserved women. PMID- 25131745 TI - Protection of horses from West Nile virus Lineage 2 challenge following immunization with a whole, inactivated WNV lineage 1 vaccine. AB - Over the last years West Nile virus (WNV) lineage 2 has spread from the African to the European continent. This study was conducted to demonstrate efficacy of an inactivated, lineage 1-based, WNV vaccine (Equip WNV) against intrathecal challenge of horses with a recent isolate of lineage 2 WNV. Twenty horses, sero negative for WNV, were enrolled and were randomly allocated to one of two treatment groups: an unvaccinated control group (T01, n=10) and a group administered with Equip WNV (T02, n=10). Horses were vaccinated at Day 0 and 21 and were challenged at day 42 with WNV lineage 2, Nea Santa/Greece/2010. Personnel performing clinical observations were blinded to treatment allocation. Sixty percent of the controls had to be euthanized after challenge compared to none of the vaccinates. A significantly lower percentage of the vaccinated animals showed clinical disease (two different clinical observations present on the same day) on six different days of study and the percentage of days with clinical disease was significantly lower in the vaccinated group. A total of 80% of the non-vaccinated horses showed viremia while only one vaccinated animal was positive by virus isolation on a single occasion. Vaccinated animals started to develop antibodies against WNV lineage 2 from day 14 (2 weeks after the first vaccination) and at day 42 (the time of onset of immunity) they had all developed a strong antibody response. Histopathology scores for all unvaccinated animals ranged from mild to very severe in each of the tissues examined (cervical spinal cord, medulla and pons), whereas in vaccinated horses 8 of 10 animals had no lesions and 2 had minimal lesions in one tissue. In conclusion, Equip WNV significantly reduced the number of viremic horses, the duration and severity of clinical signs of disease and mortality following challenge with lineage 2 WNV. PMID- 25131746 TI - Efficacy of live attenuated influenza vaccine against influenza illness in children as a function of illness severity. AB - A recent study of inactivated influenza vaccine (IIV) in children aged 3-8 years demonstrated higher efficacy against moderate/severe influenza. A meta-analysis of all previous published randomized clinical trials of live attenuated influenza vaccine (LAIV) that collected information on illness severity in children aged 24 71 months was conducted. Moderate/severe influenza was defined as fever >39 degrees C, acute otitis media, or lower respiratory tract illness; other cases were classified as milder influenza. LAIV efficacy versus placebo was 95.4% [95% confidence interval: 88.5, 98.1] (year 1) and 88.5% [77.4, 94.9] (year 2) against moderate/severe influenza and 91.4% [77.9, 96.7] (year 1) and 84.2% [56.7, 94.3] (year 2) against milder influenza. The relative efficacy of LAIV versus IIV was 52.2% [31.6, 66.6] for moderate/severe influenza and 45.0% [28.6, 57.5] for milder influenza. Efficacy against all influenza illnesses, regardless of severity, is critical to prevent influenza illness and transmission in the community. PMID- 25131747 TI - Fluorescence-guided resection of high-grade gliomas: a systematic review and meta analysis. AB - OBJECTIVE: The present systematic review and meta-analysis was to analyze of the advantages of intraoperative fluorescence-guided resection of high-grade gliomas. METHODS: Systematic computerized searches of the PubMed and Web of Knowledge were performed. The outcomes included diagnostic value for identification of tumor tissue, gross total resection, and prognosis. The summary receiver operating characteristic curves (SROC), the pooled sensitivities, the pooled specificities, the pooled odd ratio (OR) and the pooled hazard ratio (HR) were estimated by meta analysis. RESULTS: Twelve studies were included. The pooled sensitivity and the pooled specificity for identification of tumor tissue was 0.84 (95% CI: 0.81 0.87), and 0.91 (95% CI: 0.87-0.94), respectively. And the overall weighted AUC of the SROC curve was 0.9520 +/- 0.0116. The summary OR of the gross total resection rate in patients with fluorescein-guided resection compared with patients with no fluorescein was 4.372 (95% CI 2.937-6.508). Fluorescein-guided resection was associated with a reduced risk of progression-free survival compared with no fluorescein, with HR 0.73 (95% CI 0.57-0.94, P = 0.01). The pooled HR of overall survival was 1.000 (95% CI 0.960-1.040) between two groups. No significant publication bias was found. CONCLUSION: Fluorescence-guided resection of high-grade gliomas is effective for diagnosing tumor margins, increasing gross total resection, and reducing the risk of progression-free survival. But this conclusion should be confirmed by large sample randomized controlled clinical trials. PMID- 25131749 TI - Structural effect on the resistive switching behavior of triphenylamine-based poly(azomethine)s. AB - Linear and hyperbranched poly(azomethine)s (PAMs)-based on triphenylamine moieties are synthesized and used as the functioning layers in the Ta/PAM/Pt resistive switching memory devices. Comparably, the hyperbranched PAM with isotropic architecture and semi-crystalline nature shows enhanced memory behaviors with more uniform distribution of the HRS and LRS resistances. PMID- 25131748 TI - Epidemiological and evolutionary characteristics of the PRRSV in Southern China from 2010 to 2013. AB - In 2006, a highly pathogenic strain of porcine reproductive and respiratory syndrome virus (HP-PRRSV) emerged in China and caused lasting damage to the swine industry. To analyze the genetic variation of PRRSV in Southern China, 126 tissue samples were collected; 41 ORF5 and partial Nsp2 genes were sequenced and analyzed. The results showed that the PRRSV positive rate was 32.54% over the last four years, that there are two main subgenotypes in Southern China, and that the dominant strain is HP-PRRSV. An amino acid analysis of Nsp2 showed that 40 strains contained a 30-amino acid deletion in the hypervariable region. However, the 13YJ6-8 mutant exhibited a unique amino acid deletion at positions 508-514 of Nsp2. A phylogenetic analysis of ORF5 revealed that this mutant and five other strains, belong to an intermediate subgenotype (inter-subgenotype), which is characterized by extensive mutations, especially in the signal peptide and N glycosylation sites. The results of this study demonstrate the genetic diversity of PRRSV in Southern China and provide basic knowledge of the PRRSV epidemic in this region. PMID- 25131750 TI - 4-bromopropofol decreases action potential generation in spinal neurons by inducing a glycine receptor-mediated tonic conductance. AB - BACKGROUND AND PURPOSE: Impaired function of spinal strychnine-sensitive glycine receptors gives rise to chronic pain states and movement disorders. Therefore, increased activity of glycine receptors should help to treat such disorders. Although compounds targeting glycine receptors with a high selectivity are lacking, halogenated analogues of propofol have recently been considered as potential candidates. Therefore we asked whether 4-bromopropofol attenuated the excitability of spinal neurons by promoting glycine receptor-dependent inhibition. EXPERIMENTAL APPROACH: The actions of sub-anaesthetic concentrations of propofol and 4-bromopropofol were investigated in spinal tissue cultures prepared from mice. Drug-induced alterations in action potential firing were monitored by extracellular multi-unit recordings. The effects on GABAA and glycine receptor-mediated inhibition were quantified by whole-cell voltage-clamp recordings. KEY RESULTS: Low concentrations of 4-bromopropofol (50 nM) reduced action potential activity of ventral horn neurons by about 30%, compared with sham-treated slices. This effect was completely abolished by strychnine (1 MUM). In voltage-clamped neurons, 4-bromopropofol activated glycine receptors, generating a tonic current of 65 +/- 10 pA, while GABAA - and glycine receptor mediated synaptic transmission remained unaffected. CONCLUSIONS AND IMPLICATIONS: The highest glycine levels in the CNS are found in the ventral horn of the spinal cord, a region mediating pain-induced motor reflexes and participating in the control of muscle tone. 4-Bromopropofol may serve as a starting point for the development of non-sedative, non-addictive, muscle relaxants and analgesics to be used to treat low back pain. PMID- 25131753 TI - From the Editor's perspective.... PMID- 25131752 TI - Myeloid-derived tissue-type plasminogen activator promotes macrophage motility through FAK, Rac1, and NF-kappaB pathways. AB - Macrophage accumulation is one of the hallmarks of progressive kidney disease. Tissue-type plasminogen activator (tPA) is known to promote macrophage infiltration and renal inflammation during chronic kidney injury. However, the underlying mechanism remains largely unknown. We examined the role of tPA in macrophage motility in vivo by tracking fluorescence-labeled bone marrow-derived macrophages, and found that tPA-deficient mice had markedly fewer infiltrating fluorescence-labeled macrophages than the wild-type (WT) mice. Experiments in bone marrow chimeric mice further demonstrated that myeloid cells are the main source of endogenous tPA that promotes macrophage migration. In vitro studies showed that tPA promoted macrophage motility through its CD11b-mediated protease independent function; and focal adhesion kinase (FAK), Rac-1, and NF-kappaB were indispensable to tPA-induced macrophage migration as either infection of FAK dominant-negative adenovirus or treatment with a Rac-1-specific inhibitor or NF kappaB inhibitor abolished the effect of tPA. Moreover, ectopic FAK mimicked tPA and induced macrophage motility. tPA also activated migratory signaling in vivo. The accumulation of phospho-FAK-positive CD11b macrophages in the obstructed kidneys from WT mice was clearly attenuated in tPA knockout mice, which also displayed lower Rac-1 activity than their WT counterparts. Therefore, our results indicate that myeloid-derived tPA promotes macrophage migration through a novel signaling cascade involving FAK, Rac-1, and NF-kappaB. PMID- 25131751 TI - Who are the children using hospice care? AB - PURPOSE: The purpose was to examine the characteristics of children who use hospice care. DESIGN AND METHODS: Using the Andersen Model of Health Services Use, California Medicaid administrative databases were analyzed to describe the characteristics of 76 children in hospice. RESULTS: The predisposing, enabling, and need characteristics of children were identified. Children who used hospice were a diverse group with community resources that enabled them to access care while presenting with serious health needs. Children enrolled in hospice were more likely older (15-20 years of age), resided nearer a pediatric hospice, and had a serious health condition such as neuromuscular disease with multiple comorbidities. PRACTICE IMPLICATIONS: With this knowledge, pediatric nurses can improve their clinical practice by targeting conversations with families and children most in need of hospice care. PMID- 25131754 TI - Evaluation of the perception of chronic ischemic pain in humans with peripheral arterial disease. AB - The perception of pain is multidimensional, subjective, and unique to each individual and can be influenced by several dimensions of pain. The objective of this study was to evaluate the perception of chronic ischemic pain using the descriptors of pain and to rate the main descriptors of chronic pain to people with peripheral arterial disease (PAD). The study was conducted in two hospitals in Brazil and consisted of two phases. In phase I, 100 participants with a diagnosis of PAD and chronic pain evaluated 50 descriptors of pain using the Multidimensional Pain Evaluation Scale by the psychophysical method of category estimation using a numerical scale with 11 points. In phase II, 30 participants judged the 10 first descriptors selected in phase I by the psychophysical method of magnitude estimation. The average intensity of chronic ischemic pain was 5.59 +/- 3.16. The descriptors of chronic pain with higher scores obtained by the method of category estimation were unpleasant, followed by disturbing, strong, concern, tiring, boring, terrible, painful, sickening, and uncomfortable. By the method of magnitude estimation, the descriptors of pain showing sensitive, affective, and cognitive dimensions were identified by the descriptors terrible, follow by painful, uncomfortable, concern, tiring, sickening, strong, disturbing, boring, and unpleasant. This study showed that the chronic ischemic pain by PAD is associated with multidimensional components of pain. PMID- 25131756 TI - Cardiovascular risk profile of veteran men beginning androgen deprivation therapy. AB - We sought to describe the cardiovascular profile of veteran men before beginning androgen deprivation therapy (ADT), with the eventual benefit of targeting treatments to manage harmful cardiovascular side effects. We performed a secondary analysis with chi-square and Fisher's exact tests for associations between demographics and cardiovascular comorbidities on 375 veteran men diagnosed with prostate cancer. Those who were overweight and current smokers were more likely to be younger, whereas men with a systolic blood pressure >120 mmHg were more likely to be older (all P < 0.05). Men with total cholesterol 180 mg/dL were more likely to be identified in the Hispanic/other/unknown ethnicity category. Interventions to manage cardiovascular risk should focus on preventive lifestyle changes for younger men, and chronic disease management for older men. Men in the smaller Hispanic/other/unknown category are at risk for marginalization within the Veteran Administration system owing to their low numbers and should be closely monitored for cholesterol levels when receiving ADT. PMID- 25131755 TI - Patient perspectives on information needs for amputation secondary to vascular surgery: what, when, why, and how much? AB - In patients undergoing an amputation secondary to vascular disease, little is known about the timing, mode of delivery, or amount of information needed. The purpose of this study was to explore the perspectives of patients who have undergone a major lower limb amputation as a result of vascular disease, regarding the information healthcare professionals should provide to them during their acute hospital stay. A qualitative study using descriptive methodology was used. Patients were included if they had a major lower limb amputation 1 week to 2 years before the interview. Purposive sampling was used. Sixteen patients participated in a semistructured interview, either face to face or by telephone. Interviews were transcribed verbatim. Thematic analysis was used. Transcripts were coded by two researchers and compared. N-vivo, descriptive and interpretative analyses were used to assess transcribed interviews. Patients stated that there was insufficient information on a variety of topics, including the recovery process, expectations for rehabilitation, and prosthetics. They went on to describe that high pain levels, age, and emotional status affected the delivery of information to them. Patients had different perspectives on timing of information, mode of delivery, and amount of information. An individualized approach to the delivery of information should be considered for patients undergoing major lower limb amputation. Involved healthcare professionals need to take into consideration patient-specific preferences and unique educational needs before the delivery of information. We anticipate that findings from this study will influence the development of an educational program to deliver effective patient centered care in this unique patient population. PMID- 25131757 TI - The predictors of surgical site infection post cardiac surgery: a systematic review. AB - We sought to conduct a systematic review to evaluate the predictors of surgical site infection (SSI) after cardiac surgery. We included published, peer-reviewed, English-language, retrospective and prospective studies identified in a search of Medline, CINAHL, and PubMed from 2005 and through February 20, 2012. The studies involved adults (age >18 years) undergoing cardiac surgery (defined by ICD-9 codes) and could be of any study design, in English, published within last 7 years, with data collection taking place in United States within last 10 years. We excluded animal studies, duplicates, summaries, commentaries, editorials, case reports, studies that conducted outside United States, and studies published before last 7 years or studies with data collection take place before last 10 years (2002). Three types of predictors emerge: Predictors of general infection post cardiac surgery, predictors of micro-organisms' specific SSIs and tracheotomy, and allogenic blood transfusion as specific predictors of SSI. Although the reviewed articles cover wide range of SSIs predictors, none of these articles investigate preoperative skin preparation, using pre- and postoperative prophylaxes antibiotics, postoperative wound care (appropriate time for first dressing), and patient nutritional status as a predictors of SSIs after cardiac surgery. Investigating these predictors for SSIs will enhance nurses' understanding of the importance of specific types of nutrition in preventing SSIs and enhancing wound healing, implementing a protocol for the wound care postoperatively, and implementing a protocol for the use of prophylactic antibiotics. PMID- 25131758 TI - Same-day discharge after angioplasty for peripheral vascular disease: is it a safe and feasible option? AB - Peripheral vascular disease affects 20% of the population >55 years of age. Patients who become symptomatic are managed by a number of technique's including medical management, percutaneous angioplasty, bypass surgery, and in nonreconstructable situations, limb amputation. Clinicians treating patients by means of angioplasty have traditionally carried out these procedures on an inpatient basis. Limited resources and pressure on the availability of inpatient beds has necessitated clinicians to reevaluate how many of these patients are managed. Treating suitable patients as day cases is an attractive option that frees up resources and is financially advantageous. This paper examines the feasibility of same-day discharge after angioplasty, with a particular emphasis on achieving safe patient outcomes. It explores how advances in endovascular technologies and techniques have contributed to making same-day discharge an ever more feasible option. Nurse led pre-admission clinics run by specialist nurses facilitate safe and appropriate patient selection, where patients at risk for postprocedural problems can be identified effectively based on predefined clinical criteria. PMID- 25131759 TI - Review of article: Effectiveness of combined therapy with angiotensin-converting enzyme inhibitors and statins in reducing mortality in diabetic patients with critical limb ischemia: an observational study by Ezio Faglia, Giacomo Clerici, Alessia Scatena et al (Diabetes Research and Clinical Practice 2014;103:292-297). PMID- 25131760 TI - Review of article: Hypertension in 2014 making sense of the guidelines by Kristine Anne Scordo, PhD, RN, ACNP-BC, FAANP, Kim Anne Pickett, MS, APRN, CDE (Nurse Practitioner 2014;39:18-23). PMID- 25131761 TI - Carcinogenic mechanisms of endometrial cancer: involvement of genetics and epigenetics. AB - Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen-dependent proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; hypermethylation of the MMR gene hMLH1; mutation of PTEN, beta-catenin and K-ras genes in type I endometrial cancer and of HER-2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A, RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR 124, miR-126, miR-137, miR-491, miR-129-2 and miR-152. Thus, it is likely that the carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Mutations and methylation of MMR genes induce various oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells and methylation patterns may be inherited over generations and cause familial tumorigenesis. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting MMR genes. PMID- 25131762 TI - Highly improved perinatal states in Japan. AB - To report on improved perinatal states in Japan, governmental and United Nations Children's Fund reports were analyzed. Initial maternal mortality, which was 409.8 in 1899, decreased to 4.1 in 2010, with a reduction rate of 409.8/4.1 (102.4) in 111 years: 2.5 in the initial 50 years in home delivery and 39.3 in the later 60 years in hospital births. The difference between 2.5 versus 39.3 was attributed to the medicine and medical care provided in hospital births. The total reduction of neonatal mortality was 77.9/1.1 (70.8), and the rate in the initial 50 versus later 60 years was 2.8/25. Also, there was a big difference after introduction of extensive neonatal care. Virtual perinatal mortality after 22 weeks was estimated to be 428 in 1000 births in 1900 (i.e. those infants born at 22-28 weeks were unlikely to survive at that time), while the perinatal mortality was reported to be 22 weeks or more in 1979 (i.e. premature babies born at >=22 weeks survived in 1979 because of the improved neonatal care). Actually, 60% of premature infants of 400-500 g survived in the neonatal intensive care unit. In a recent report, 36% of infants born at 22 weeks survived to 3 years. Although there were neurodevelopmental impairments, outcomes were improved. In conclusion, perinatal states have remarkably improved in Japan. PMID- 25131763 TI - Marriage and child bearing in patients with transfusion-dependent thalassemia major. AB - AIM: With good care, patients with transfusion-dependent thalassemia major (TDTM) can reach older ages, marry and reproduce. This study was conducted by the Thalassemia Research Center. MATERIAL AND METHODS: Medical notes of all TDTM patients and all non-transfusion-dependent thalassemia major (NTDTM) patients were reviewed from July to December 2012. Also, patients were interviewed. The questionnaire was made in consultation with research methodology experts and reliability was achieved by a pilot study of 12 patients, by the test-retest method (r = 0.9). Epidemiologic characteristics of patients and the pregnancy outcomes were recorded. Descriptive statistics were used with SPSS 17. RESULTS: Four hundred and nineteen medical records were reviewed. Three hundred and forty five (82.5%) were TDTM. One hundred and seventy-five (50.7%) were female with a mean age of 25.4 +/- 7.05 years and 42 (25%) had been married. Mean age of menarche and marriage was 15.4 +/- 1.6 and 21.8 +/- 4.5 years, respectively. Total number of live children is nine so far. Mode of delivery in female patients was cesarean section. Almost 78% of newborns weighed 2500-4000 g. Almost 22% of pregnancies were assisted. Male patients consisted of 170 (49.3%) and 55 (32.3%) of them had been married. Mean age at marriage was 24.27 +/- 3.5 years. CONCLUSIONS: With better management, patients with TDTM can reach the age of reproduction. Medical teams should be prepared for this possibility. PMID- 25131764 TI - Laparoscopic cornuotomy for interstitial pregnancy and postoperative course. AB - AIM: The aim of this study was to evaluate the advantages of laparoscopic cornuotomy in treating interstitial pregnancy, and the effect of the procedure on reproductive outcomes. METHODS: Thirteen patients were treated for interstitial pregnancy by laparoscopic cornuotomy with or without local methotrexate injection, between March 2000 and January 2012 at NTT East Japan Tohoku Hospital and Sendai City Hospital. The patients were followed to assess the outcomes of subsequent pregnancies for at least 1 year after the operation. RESULTS: All 13 cases of interstitial pregnancy were successfully treated by laparoscopic cornuotomy, without performing cornual resection or laparotomy. The mean gestational age was 7.6 +/- 1.3 weeks, and the average serum hCG level was 20,800 +/- 18,100 IU/L. The mean cornual mass size was 34.6 +/- 10.2 mm. Eight of the patients later obtained a spontaneous intrauterine pregnancy. Three patients that delivered by cesarean section showed no uterine dehiscence or thinning of the scar at the site of the earlier cornual incision and repair. None of the patients experienced uterine rupture. CONCLUSION: Interstitial pregnancy can be selectively treated by laparoscopic cornuotomy with local methotrexate injection, if managed carefully. PMID- 25131766 TI - Decreased expression of elastin and lysyl oxidase family genes in urogenital tissues of aging mice. AB - AIM: This study aims to investigate the expression levels of elastin and lysyl oxidase (LOX) family members in the urogenital tissues of natural aging mice and accelerated ovarian aging mice. METHOD: Uteri, vaginas and bladders were harvested from 18-month-old female mice and accelerated ovarian aging mice developed by chemotherapeutic agents. Untreated 3-month-old female mice were used as controls. The expression levels of elastin and LOX family members were determined by real-time polymerase chain reaction and western blot. RESULTS: Compared with untreated young female mice, the expression of elastin and LOX family members significantly decreased both in natural aging mice and accelerated ovarian aging mice. CONCLUSION: Aging is a high-risk factor for pelvic floor disorders. The failure of elastic fiber synthesis and assembly due to the decline in expression levels of elastin and LOX family members during aging may explain the molecular mechanism causing pelvic floor disorders. PMID- 25131765 TI - Thalidomide affects experimental endometriosis: a randomized controlled study in the rat. AB - AIM: This study aimed to assess the efficacy of thalidomide for treatment of experimental endometriosis. METHODS: This study was a parallel-group, double blind, stratified, randomized controlled animal trial with 1:1 allocation ratio. Endometriosis was induced experimentally in 23 mature, nulligravid, female Sprague-Dawley rats, weighing approximately 200 g and aged 2 months. A checkpoint surgery was performed 6 weeks later. Then, the rats were randomly allocated into the thalidomide (22 mg/day p.o.) and control (0.5 mL saline 0.9%/day p.o.) groups of nine. After 6 weeks, they were killed. Before each laparotomy, blood for leukocyte and lymphocyte counts and during them, implants for histopathology and peritoneal fluid for interleukin (IL)-6, tumor necrosis factor-alpha and vascular endothelial growth factor (VEGF)-A concentrations (by enzyme-linked immunoassay) were collected. Allocation and stratified randomization were done using a computer, based on the obtained histopathology scores of the implants of the checkpoint surgery. RESULTS: The histopathology scores (the main outcome measure) were 2.00 +/- 1.55 versus 0.44 +/- 1.01 (P = 0.035). The comparisons of after treatment counts of leukocytes, lymphocytes, VEGF-A and IL-6 between the two groups were statistically significant. CONCLUSION: The results of this study are in favor of therapeutic implication of thalidomide in experimental endometriosis in rats. This is the first time thalidomide has been evaluated on endometriosis in an animal model. PMID- 25131767 TI - Successful ex utero intrapartum treatment procedure for prenatally diagnosed severe micrognathia: a case report. AB - We present a case of fetal severe micrognathia in which successful airway stabilization was achieved by an ex utero intrapartum treatment procedure. In this case, it was anticipated that the infant would have a vulnerable airway at birth based on in utero sonographic findings, including an extremely hypoplastic jaw, worsening polyhydramnios and absence of stomach visualization. Early sonographic recognition was helpful in preparing the parents and physicians for the possibility of airway emergencies during the perinatal period. When a severely hypoplastic mandible accompanied by polyhydramnios and absent stomach visualization is noted on ultrasound, clinicians should consider the indication for ex utero intrapartum treatment. A multidisciplinary team with technically skilled medical providers should be coordinated to perform the procedure. PMID- 25131768 TI - Case of concurrent benign metastasizing leiomyoma in the lung and retroperitoneum, with a focus on its etiology. AB - We report a rare, simultaneous occurrence of benign metastasizing leiomyoma in the lung and retroperitoneum in a 49-year-old woman who had previously undergone myomectomy at 35 years of age and hysterectomy at 45 years of age for multiple recurrences of histologically benign uterine leiomyomas. At 49 years of age, computed tomography-guided biopsy indicated benign metastasizing leiomyomas in the lung. In addition, a retroperitoneal leiomyoma was found that was resected along with both the ovaries via laparotomy. No sign or symptom of recurrence was observed 5 years later. The coexistence of benign metastasizing leiomyoma in the lung and retroperitoneum following surgery for conventional leiomyomas has rarely been reported. Further, the nature and etiology of benign metastasizing leiomyoma are still not well understood. This case is therefore worth reporting, and exploring its etiology is important. PMID- 25131769 TI - Patient-reported outcome measures in pediatric epilepsy: a content analysis using World Health Organization definitions. AB - OBJECTIVE: Patient-reported outcome (PRO) measures that assess the effect of epilepsy on children's lives include the concepts of health, health-related quality of life (HRQOL), and quality of life (QOL). They also contain varied health and health-related content. Our objectives were to identify what generic and epilepsy-specific PRO instruments are used in childhood epilepsy research and to make explicit their conceptual approach and biopsychosocial content. METHODS: MEDLINE, EMBASE, and PsycINFO were searched from 2001 to 2011 for PRO measures used in pediatric epilepsy. Measures were analyzed on an item-by-item basis according to World Health Organization (WHO) definitions of QOL and the International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY) biopsychosocial health framework to distinguish the conceptual approach within each measure. The health content analysis coded each item according to specific ICF-CY components of body function, activity and participation, environment, or personal factors to determine the health content for each measure. RESULTS: Three generic and 13 epilepsy-specific PRO measures were identified; 10 of 16 measures utilized a biopsychosocial health approach rather than an HRQOL or QOL approach. Content analysis showed that in 11 of 16 measures, >25% of the items represented participation and activity components of the ICF-CY, whereas a high proportion of environment items were found in only one epilepsy-specific measure. SIGNIFICANCE: This comprehensive review provides information aiding clinicians and researchers in the selection of the appropriate PRO instruments for children with epilepsy on the basis of content. Most epilepsy specific and generic PROs use a biopsychosocial health approach as opposed to a subjective HRQOL/QOL approach to measurement. Clinicians and researchers must be aware of these concepts and content when intending to measure outcomes validly. PMID- 25131770 TI - SIRT1 regulates oncogenesis via a mutant p53-dependent pathway in hepatocellular carcinoma. AB - BACKGROUND & AIMS: SIRT1 is a class III histone deacetylase that plays diverse roles in various cancers. However, the clinical significance of SIRT1 in hepatocellular carcinoma (HCC) remains unknown. METHODS: We analysed p53 mutations and the activation of SIRT1 in 252 hepatitis B virus-positive HCC cases. None of the patients had been subjected to pre-operative treatment. RESULTS: We examined 57 p53 mutations from 248 HCC tissues. Activated SIRT1 (phosphorylated form of Ser47), in the context of mutant p53, predicted a longer relapse-free survival (RFS) but not a longer overall survival (OS) (RFS: p = 0.007, OS: p = 0.280) in HCC tissues harbouring mutant p53. In multivariate analysis, activated SIRT1 remained a significant predictor of longer RFS (OR = 0.307, CI: 0.143-0.660, p=0.002). Analysis of 248 paired specimens revealed a significant correlation between activated SIRT1 (Ser47) and activated AMPK (Thr172) in HCC tissues harbouring mutant p53 (p = 0.003, n = 57). The combination of these 2 parameters was a powerful predictor for a good prognosis in these patients. In vitro, SIRT1 inactivation stimulated the growth of HCC cells, bearing mutated p53, by suppressing AMPK activity and subsequently enhancing mammalian target of rapamycin (mTOR) activity, resulting in induction of p70S6K1 activation in HCC cells. Metformin, an AMPK activator, more strongly suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53 mutant cell lines with active SIRT1. CONCLUSIONS: SIRT1 exerted anti-carcinogenic effects via the AMPK-mTOR pathway in HCC in the context of mutant p53. Metformin could be a therapeutic drug for HCC in patients with mutated p53, inactivated SIRT1, and AMPK expression. PMID- 25131771 TI - A heterogeneous hierarchy of co-regulatory receptors regulates exhaustion of HCV specific CD8 T cells in patients with chronic hepatitis C. AB - BACKGROUND & AIMS: The functionality of virus-specific T cells is regulated by a sophisticated network of an expanding repertoire of co-regulatory receptors, which could be harnessed for immunotherapeutic applications. However, targeting particular pathways during persistent virus infections has resulted in variable outcomes. The extent to which T cell exhaustion can be reversed, by targeting multiple co-regulatory pathways, still remains not fully investigated. METHODS: We analysed the phenotype and in vitro functionality of HCV-specific CD8(+) T cells expressing PD-1, CTLA-4, TIM-3 or 2B4 either alone or in various combinations and compared expression levels to those of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) specific T cells in peripheral blood mononuclear cells (PBMCs) from the same cohort of patients with chronic hepatitis C (CHC) infection. RESULTS: Blockade and/or crosslinking of distinct co-regulatory pathways in exhausted HCV-specific CD8(+) T cells resulted in rather diverse and individualized T cell responses, irrespective of the type and number of receptors targeted. Overall, in vitro manipulations of these pathways yielded three response possibilities: (i) total non-response (ii) good single blockade response and (iii) good dual/multiple blockade response, with each comprising approximately one-third of the patients tested. The diversity of the in vitro responsiveness of HCV-specific T cells was reflected by an enormous ex vivo phenotypic heterogeneity. Despite this broad heterogeneity, HCV-specific CD8(+) T cells differed from EBV- and CMV-specific T cells in particular by TIM-3 expression, which also correlated with liver disease activity and viral load. CONCLUSIONS: HCV-specific CD8(+) T cell functionality, upon co-regulatory receptor manipulations, was characterized by an individual pattern of responses in patients with CHC, suggesting that treatment approaches, targeting these receptors, should consider inter-individual differences and be personalized. PMID- 25131772 TI - Regulatory T cells and autoimmune hepatitis: what happens in the liver stays in the liver. PMID- 25131773 TI - Effects of atorvastatin on bone mineral density (BMD) and bone metabolism in elderly males with osteopenia and mild dyslipidemia: a 1-year randomized trial. AB - We explored the effects of atorvastatin on BMD and biochemical markers of bone metabolism in a 1-year, prospective, randomized controlled study. 64 male patients with osteopenia and mild dyslipidemia (mean age 80.1+/-6.6 years) were randomized to a 1-year atorvastatin treatment or control. BMD of hip and lumbar spine was measured with dual-energy X-ray absorptionmetry (DXA). Bone metabolic markers including resorption markers beta-c-terminal telopeptide of type I collagen (CTx), formative markers osteocalcin (OC), 25-hydroxyvitamin D (25(OH)D) were measured with electrochemiluminescence immunoassay (ECLIA). Other bone metabolism markers including intact parathyroid hormone (iPTH) and testosterone were measured with chemiluminescence enzyme immunoassay (CLEIA). Levels of serum lipid and biochemical parameters were measured with automatic biochemical analyzer. All the parameters were recorded at baseline, and at 6 and 12 months, respectively. Compared with the control group, the atorvastatin treatment group showed significant reduction of triglyceride (TG, P<0.01) and low-density lipoprotein cholesterol (LDL-C, P<0.01). At 12 month, total hip BMD in atorvastatin group was significantly higher (P<0.01) compared with the control group, while there were no similar effect on femoral neck or lumbar spine between the two groups (P=0.48 and 0.53 respectively). Meanwhile, CTx significantly reduced in atorvastatin treatment group (P<0.001) compared with baseline. Our findings suggest that in elderly male patients with osteopenia and mild dyslipidemia, therapeutic doses of atorvastatin were associated with positive effects on BMD, probably mediated by suppressed bone resorption. PMID- 25131774 TI - Efficacy of an anticoccidial live vaccine in prevention of necrotic enteritis in chickens. AB - Necrotic enteritis (NE) is an important disease in poultry caused by Clostridium perfringens combined with predisposing factors, mainly eimeriosis. In the present study, we investigated the protective effect of a commercial attenuated anticoccidial live vaccine against NE in a clinical infection model using 60 day old chicks. Vaccination was performed on study day (SD) 1 with natural booster infections for 4 weeks from Eimeria spp. oocysts present in litter. On SD 28, five groups were formed (n=12): group V+/C-E- (vaccinated, uninfected), group V+/C-E+ (vaccinated, infected with Eimeria spp.), group V+/C+E+ (vaccinated, infected with clostridia and Eimeria spp.), group V-/C+E+ (unvaccinated, infected with clostridia and Eimeria spp.), and group NC (negative control). Efficacy was measured by clinical parameters, pathogen multiplication, and pathological parameters assessed during two necropsies on SD 34 and SD 40, respectively. Additionally, cytokine expression was measured in gut and spleen tissues at necropsy. Clinical signs of NE were observed only in the coinfected groups, mainly in group V-/C+E+. Accordingly, lowest body weight gain was observed in group V-/C+E+ (301.8 g from SD 28 to SD 40; group NC: 626.2 g). Oocyst excretion varied significantly (P<0.01) between all Eimeria spp. infected groups and was highest in group V-/C+E+, followed by V+/C+E+, and lowest in group V+/C-E+. NE typical intestinal lesions showed only in groups V+/C+E+ and V-/C+E+. The intestinal mucosa featured partly severe lesions in the jejunum, C. perfringens colonization was histologically visible. Upregulation of IFN-gamma, was observed in the jejunal tissue of group V-/C+E+ (P<0.01 (SD 34) or P<0.05 (SD 40) compared to all other groups). IL-10 and IL-12 were upregulated in group V-/C+E+, IL-10 also in group V+/C+E+ (SD 40) while IL-2 expression remained unaltered. In conclusion, vaccination against coccidiosis was effective in preventing NE in a mixed infection comparable to field situations. PMID- 25131775 TI - Insights into the olfactory system of the ectoparasite Caligus rogercresseyi: molecular characterization and gene transcription analysis of novel ionotropic receptors. AB - Although various elements of the olfactory system have been elucidated in insects, it remains practically unstudied in crustaceans at a molecular level. Among crustaceans, some species are classified as ectoparasites that impact the finfish aquaculture industry. Thus, there is an urgent need to identify and comprehend the signaling pathways used by these in host recognition. The present study, through RNA-seq and qPCR analyses, found novel transcripts involved in the olfactory system of Caligus rogercresseyi, in addition to the transcriptomic patterns expressed during different stages of salmon lice development. From a transcriptomic library generated by Illumina sequencing, contigs that annotated for ionotropic receptors and other genes implicated in the olfactory system were identified and extracted. Full length mRNA was obtained for the ionotropic glutamate receptor 25, which had 3923 bp, and for the glutamate receptor ionotropic kainate 2, which had 2737 bp. Furthermore, two other transcripts identified as glutamate receptor, ionotropic kainate 2-like were found. In silico analysis was performed for the transcription expression from different stages of development in C. rogercresseyi, and clusters according to RPKM values were constructed. Gene transcription data were validated through qPCR assays in ionotropic receptors, and showed an expression of glutamate receptor 25 associated with the copepodid stage whereas adults, especially male adults, were associated with the kainate 2 and kainate 2-like transcripts. Additionally, gene transcription analysis of the ionotropic receptors showed an overexpression in response to the presence of masking compounds and immunostimulant in salmon diets. This response correlated to a reduction in sea lice infection following in vivo challenge. Diets with masking compounds showed a decrease of lice infestation of up to 25%. This work contributes to the available knowledge on chemosensory systems in this ectoparasite, providing novel elements towards understanding the host-finding process of the salmon louse C. rogercresseyi. PMID- 25131776 TI - Rhodnius prolixus: modulation of antioxidant defenses by Trypanosoma rangeli. AB - Trypanosoma rangeli is a protozoan parasite of insects and mammals that is challenged by the constant action of reactive oxygen species, generated either by its own metabolism or through the host immune response. The aim of this work was to investigate whether T. rangeli is able to modify the redox state of its insect vector, Rhodnius prolixus, through the modulation of such antioxidant enzymes as superoxide dismutase (SOD), catalase, and GPx present in the midgut of the insect. We verified that in R. prolixus fed with blood infected with T. rangeli there is an increase in SOD activity in the anterior and posterior midguts. However, the activities of enzymes related to hydrogen peroxide and hydroperoxides metabolism, such as catalase and GPx, were decreased in relation to the insect control group, which was only fed blood. These changes in the redox state of the vector led to an increase in lipid peroxidation and thiol oxidation levels in the anterior and posterior midgut tissues. We also verified that the addition of 1 mM GSH in the blood meal of the infected insects increased the proliferation of these parasites by 50%. These results suggest that there is an increase in oxidative stress in the insect gut during T. rangeli infection, and this condition could contribute to the control of the proliferation of these parasites. PMID- 25131777 TI - One minute ultraviolet exposure inhibits Toxoplasma gondii tachyzoite replication and cyst conversion without diminishing host humoral-mediated immune response. AB - We developed a protocol to inactivate Toxoplasma gondii (T. gondii) tachyzoites employing 1 min of ultraviolet (UV) exposure. We show that this treatment completely inhibited parasite replication and cyst formation in vitro and in vivo but did not affect the induction of a robust IgG response in mice. We propose that our protocol can be used to study the contribution of the humoral immune response to rodent behavioral alterations following T. gondii infection. PMID- 25131779 TI - Breast health in developing countries. AB - Breast cancer is one of the leading cancers world-wide. While the incidence in developing countries is lower than in developed countries, the mortality is much higher. Of the estimated 1 600 000 new cases of breast cancer globally in 2012, 794 000 were in the more developed world compared to 883 000 in the less developed world; however, there were 198 000 deaths in the more developed world compared to 324 000 in the less developed world (data from Globocan 2012, IARC). Survival from breast cancer depends on two main factors--early detection and optimal treatment. In developing countries, women present with late stages of disease. The barriers to early detection are physical, such as geographical isolation, financial as well as psychosocial, including lack of education, belief in traditional medicine and lack of autonomous decision-making in the male dominated societies that prevail in the developing world. There are virtually no population-based breast cancer screening programs in developing countries. However, before any screening program can be implemented, there must be facilities to treat the cancers that are detected. Inadequate access to optimal treatment of breast cancer remains a problem. Lack of specialist manpower, facilities and anticancer drugs contribute to the suboptimal care that a woman with breast cancer in a low-income country receives. International groups such as the Breast Health Global Initiative were set up to develop economically feasible, clinical practice guidelines for breast cancer management to improve breast health outcomes in countries with limited resources. PMID- 25131780 TI - Perineuronal net, CSPG receptor and their regulation of neural plasticity. AB - Perineuronal nets (PNNs) are reticular structures resulting from the aggregation of extracellular matrix (ECM) molecules around the cell body and proximal neurite of specific population of neurons in the central nervous system (CNS). Since the first description of PNNs by Camillo Golgi in 1883, the molecular composition, developmental formation and potential functions of these specialized extracellular matrix structures have only been intensively studied over the last few decades. The main components of PNNs are hyaluronan (HA), chondroitin sulfate proteoglycans (CSPGs) of the lectican family, link proteins and tenascin-R. PNNs appear late in neural development, inversely correlating with the level of neural plasticity. PNNs have long been hypothesized to play a role in stabilizing the extracellular milieu, which secures the characteristic features of enveloped neurons and protects them from the influence of malicious agents. Aberrant PNN signaling can lead to CNS dysfunctions like epilepsy, stroke and Alzheimer's disease. On the other hand, PNNs create a barrier which constrains the neural plasticity and counteracts the regeneration after nerve injury. Digestion of PNNs with chondroitinase ABC accelerates functional recovery from the spinal cord injury and restores activity-dependent mechanisms for modifying neuronal connections in the adult animals, indicating that PNN is an important regulator of neural plasticity. Here, we review recent progress in the studies on the formation of PNNs during early development and the identification of CSPG receptor - an essential molecular component of PNN signaling, along with a discussion on their unique regulatory roles in neural plasticity. PMID- 25131778 TI - Tissue inhibitor of metalloproteinases (TIMP)-1 creates a premetastatic niche in the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice. AB - Due to its ability to inhibit prometastatic matrix metalloproteinases, tissue inhibitor of metalloproteinases (TIMP)-1 has been thought to suppress tumor metastasis. However, elevated systemic levels of TIMP-1 correlate with poor prognosis in cancer patients, suggesting a metastasis-stimulating role of TIMP-1. In colorectal cancer patients, tumor as well as plasma TIMP-1 levels were correlated with synchronous liver metastasis or distant metastasis-associated disease relapse. In mice, high systemic TIMP-1 levels increased the liver susceptibility towards metastasis by triggering the formation of a premetastatic niche. This promoted hepatic metastasis independent of origin or intrinsic metastatic potential of tumor cells. High systemic TIMP-1 led to increased hepatic SDF-1 levels, which in turn promoted recruitment of neutrophils to the liver. Both inhibition of SDF-1-mediated neutrophil recruitment and systemic depletion of neutrophils reduced TIMP-1-induced increased liver susceptibility towards metastasis. This indicates a crucial functional role of neutrophils in the TIMP-1-induced premetastatic niche. CONCLUSION: Our results identify TIMP-1 as an essential promoter of hepatic premetastatic niche formation. PMID- 25131781 TI - [Bicarbonate reabsorption in proximal renal tubule: molecular mechanisms and metabolic acidosis]. AB - HCO3(-) reabsorption in the renal tubules plays a critically important role in maintaining the global acid-base balance. Loss of HCO3(-) causes metabolic acidosis. Proximal renal tubule is the major site for HCO3(-) reabsorption, accounting for more than 80% of total HCO3(-) reabsorption along the nephron. Over the past more than half centuries, tremendous progresses have been made on understanding the molecular mechanisms underlying the HCO3(-) reabsorption in proximal tubules. The transepithelial movement of HCO3(-) involves the coordinated operation of machineries on both the apical and the basolateral membranes of the epithelial cells. On the apical domain, Na(+)-H(+) exchanger NHE3 and the vacuolar H(+)-ATPase are two major pathways mediating the apical uptake of HCO3(-)-related species. Taken together, NHE3 and H(+)-ATPase are responsible for about 80% of HCO3(-) reabsorption in the proximal tubule. The remaining 20% is likely mediated by pathways yet to be characterized. On the basolateral membrane, NBCe1 represents the only major known pathway mediating the extrusion of HCO3(-) coupled with Na(+) into the interstitial space. In the present article, we provide a historical view about the studies on the mechanisms of HCO3(-) reabsorption since 1940s. Moreover, we summarize the latest progresses emerging over the past decade in the physiological as well as pathological roles of acid-base transporters underlying the HCO3(-) reabsorption in proximal tubules. PMID- 25131782 TI - [Progress on Hedgehog signaling transduction]. AB - Hedgehog (Hh) signaling pathway plays an important role during embryonic development and pattern formation. Disruption of Hh pathway results in various developmental disorders and increasing cancer incidence. Here we provide a comprehensive review of the pathway members, focusing on how mammalian Hh regulates the Gli family of transcription factors through its downstream members, the so-called "canonical signaling pathway". Hh signaling pathway is highly conserved among species, and primary cilia plays an important role as a "signaling center" during vertebrate signal transduction. Further, in the past few years, numerous studies have shown that Hh signal can also be transduced through Gli-independent ways collectively referred to as "non-canonical signaling pathways", which can be subdivided into two modules: (i) those not requiring Smo and (ii) those downstream of Smo that do not require Gli transcription factors. Thus, we review the rapid progress on canonical and non-canonical Hh pathways. PMID- 25131783 TI - [HCN ion channel: biological characteristics and functions in pain]. AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in vertebrate are reverse voltage-dependent, and its activation depends on the hyperpolarization of cell and may be directly or indirectly regulated by the cyclic adenosine monophosphate (cAMP) or other signal transduction cascades. The distribution, quantity, and activation states of HCN channels differ in tissues throughout the body. By modulating If/If current, HCN channels may influence the resting membrane potential, and thus importantly regulate neuronal excitability, dendritic integration of synaptic potentials, and synaptic transmission. Evidence exhibits that HCN channels participate in pain and other physiological and pathological process. Pharmacological treatment targeting HCN channels is of benefit to relieve pain and other related diseases. PMID- 25131784 TI - [Upregulation of P2X3 receptors in dorsal root ganglion of TRPV1 knockout female mice]. AB - The study was aimed to investigate the changes in mechanical pain threshold in the condition of chronic inflammatory pain after transient receptor potential vanilloid 1 (TRPV1) gene was knockout. Hind-paw intraplantar injection of complete freund's adjuvant (CFA, 20 MUL) produced peripheral inflammation in wild type and TRPV1 knockout female mice. The mechanical pain thresholds were measured during the 8 days after injection and pre-injection by using Von-Frey hair. Nine days after injection, mice were killed and the differences of expression of c-Fos and P2X3 receptor in the dorsal root ganglia (DRG) and spinal cord dorsal horn were examined by Western blotting between the two groups. Compared with that in wild-type mice, the mechanical pain threshold was increased significantly in TRPV1 knockout mice (P < 0.05); 3 days after CFA injection, the baseline mechanical pain threshold in the TRPV1 knockout mice group was significantly higher than that in the wild-type mice group (P < 0.05); The result of Western blotting showed that the expression of c-Fos protein both in DRG and spinal cord dorsal horn of TRPV1 knockout mice group was decreased significantly compared with that in wild-type mice group (P < 0.01, P < 0.05), while the expression of P2X3 receptor in DRG of TRPV1 knockout mice group was increased significantly compared with that in wild-type mice group (P < 0.05). Our findings indicate that TRPV1 may influence the peripheral mechanical pain threshold by mediating the expression of c-Fos protein both in DRG and spinal cord dorsal horn and changing the expression of P2X3 receptor in DRG. PMID- 25131785 TI - [Effect of pulse magnetic field on distribution of neuronal action potential]. AB - The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 MUA and 0 MUA. When the working current was higher than 0 MUA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 MUA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation. PMID- 25131786 TI - [MrgC receptor activation reverses chronic morphine-evoked alterations of glutamate transporters and nNOS in rats]. AB - This study was aimed to investigate the mechanisms underlying the modulation effect of Mas-related gene (Mrg) C receptors (MrgC) on morphine tolerance. Saline, morphine (20 MUg), morphine plus bovine adrenal medulla 8-22 (BAM8-22, 1 nmol) or (Tyr(6))-2-MSH-6-12 (MSH, 5 nmol) were administered intrathecally in rats for 6 days. Pain-related molecules in the spinal cord and dorsal root ganglion (DRG) were examined using Western blot, immunocytochemistry and RT-PCR techniques. The results showed that intrathecal administration of the selective MrgC receptor agonists (BAM8-22 or MSH) remarkably attenuated or abolished chronic morphine-evoked reduction in glutamate transporters (GLAST, GLT-1 and EAAC1) in the spinal cord and increase in neuronal nitric oxide synthase (nNOS) in the spinal cord as well as DRG. In addition, MrgC receptor-like immunoreactivity (IR) was detected in superficial laminae of the spinal cord. Chronic morphine induced significant increases in MrgC receptor-IR in the spinal cord and MrgC receptor mRNA levels in DRG. These results suggest that the modulation of pro-nociceptive mediators in the spinal cord and DRG underlies the inhibition of morphine tolerance by MrgC receptor activation. PMID- 25131787 TI - [Characteristic research of Uyghur and Chinese semantic cognition in event related potentials]. AB - The present study investigated the characteristic of semantic cognition of Uyghur Chinese bilinguals. The event-related potentials (ERP) technique was used to explore the characteristic of N400 wave and topographic map of difference-waves with "picture-word" semantic priming paradigm. There were significant semantic priming effects on two languages. The average amplitude of N400 was similar in two languages, while average amplitudes of three electrodes (F3, F4, PZ) in Chinese were negative than others. Meanwhile, the activation of topographic map of Uyghur was almost in all regions except occipital lobe, and the degree of activation of Chinese was less than Uyghur, but the activation in parietal and bilateral frontal lobes was higher. In conclusion, the present study suggests that two languages of Uyghur-Chinese bilinguals are all sensitive to semantic priming. The bilateral frontal and parietal lobes participate in language switching. Semantic cognition of two languages in Uyghur-Chinese late non proficient bilinguals is both completed by bilateral cerebral hemispheres. We have not found obvious lateralization on two languages of Uyghur-Chinese bilinguals. PMID- 25131788 TI - [Activation of TNF-alpha and signaling pathway in the hypothalamus of the rats subjected to chronic unpredictable mild stressors after middle cerebral artery occlusion]. AB - This study was aimed to investigate the changes of the hypothalamic-pituitary adrenal axis (HPAA) activity and the cytokines system in the hypothalamus of the depressive rats which were exposed to chronic unpredictable mild stressors (CUMS) after middle cerebral artery occlusion (MCAO). By means of qRT-PCR, ELISA and Western blot, mRNA and/or protein expressions of corticotropin releasing factor (CRF), tumor necrosis factors-alpha (TNF-alpha), suppressor of cytokines signaling 3 (SOCS3), phosphorylation of signal transducers and activators of transcription 3 (pSTAT3) were measured in the hypothalamus of rats. The results showed that, compared with control group, CUMS+MCAO group exhibited increased mRNA levels of CRF, TNF-alpha, SOCS3, as well as up-regulated CRF, TNF-alpha, SOCS3 and pSTAT3 protein expressions. Furthermore, there were correlations between CRF and TNF-alpha, TNF-alpha and SOCS3, SOCS3 and pSTAT3, respectively. These observations indicated the CRF system was activated in the post stroke depression (PSD) status. The TNF-alpha and its signaling pathway, STAT3/SOCS3, were up-regulated in mRNA and protein levels. In conclusion, this study presents the evidence which supports the hypothesis of signaling cross-talk between the CRF system and TNF-alpha signaling pathway after ischemic stroke and CUMS. PMID- 25131789 TI - [Effect of high-mobility group box 1 on the proliferation of primary neural stem cells in vitro]. AB - The cell counting kit-8 (CCK-8) proliferation assay and diameter measure of neurospheres were used to investigate the effect of high-mobility group box 1 (HMGB1) on proliferation of primary rat neural stem cells (NSCs) in vitro, and c Jun N-terminal protein kinase (JNK) potent inhibitor SP600125 was used to study the mechanism. The results demonstrated that HMGB1 significantly increased CCK-8 absorbance values and neurosphere diameters at concentrations of 1 and 10 ng/mL at 48 h and 72 h (P < 0.05), and the other HMGB1 concentration groups (0.01, 0.1, 100 ng/mL) showed no significant difference, compared with control group (P > 0.05). HMGB1 at 10 ng/mL significantly increased the NSCs proliferation accompanied by the rising of phosphorylated JNK levels (P < 0.01), and 10 MUmol/L SP600125 prevented these effects in HMGB1-cultured NSCs (P < 0.01). In conclusion, low concentration of HMGB1 (1-10 ng/mL) can increase NSCs proliferation, which may play a role by promoting JNK phosphorylation. PMID- 25131790 TI - [2-Bromoethylamine protects vascular endothelium by inhibiting SSAO activity in diabetic rats]. AB - The purpose of this study was to investigate the change of aortic semicarbazide sensitive amine oxidase (SSAO) activity in diabetic rats and examine the effect of 2-bromoethylamine (2-BEA) on SSAO activity and vascular endothelium in diabetic rats. SSAO was prepared from rat aorta. For assessment of the inhibitory effect, the enzymes were preincubated in the presence of different concentrations of 2-BEA before the addition of benzylamine in vitro. Type 1 diabetic rat model was induced by a single intraperitoneal injection of streptozotocin (STZ). Sprague Dawley (SD) rats were randomly divided into normal control group (NC), diabetic model group (DM), 2-BEA 5 mg/kg group, 2-BEA 20 mg/kg group (n = 10 in each group). 2-BEA was administered daily via intraperitoneal injection for 8 weeks. At the end of 8 weeks, blood sample was collected from the abdominal aorta. Plasma nitric oxide (NO) was determined by nitrate reductase method. Plasma endothelin-1 (ET-1) was determined by radioimmunoassay. Aorta SSAO was determined by high performance liquid chromatography. The aorta was prepared to observe morphological changes and ultramicroscopic structures. The results were as follows: Compared with NC group, aortic SSAO activity and the plasma ET-1 were significantly increased (P < 0.01), and plasma NO was significantly decreased (P < 0.01) in DM group. 2-BEA decreased plasma ET-1 and elevated plasma NO by inhibiting aortic SSAO activity in diabetic rats (P < 0.01), and 2-BEA 20 mg/kg group was more significant than 2-BEA 5 mg/kg group (P < 0.05). Endothelial injury of 2-BEA group rats was less serious than DM group. These results suggest that 2-BEA protect aortic endothelium by inhibiting aortic SSAO activity. PMID- 25131791 TI - [Abnormal calcium re-uptake in myocardium sarcoplasmic reticulum in rabbits with heart failure and the influencing factors]. AB - The aim of the present study was to investigate the abnormal calcium re-uptake function of myocardium sarcoplasmic reticulum (SR) in rabbits with heart failure, as well as potential mechanisms. Heart failure model was established in rabbits through aortic insufficiency and constriction of abdominal aorta. The SR Ca(2+) re-uptake function was measured with a calcium imaging device. The activity of myocardium SR calcium adenodine triphosphatase 2a (SERCA2a) was measured by inorganic phosphate. The protein expressions of SERCA2a, CaMKII, PKA, PP1alpha, phospholamban (PLB), PLB-Ser(16) and PLB-Thr(17) were evaluated by Western blot. The activities of PKA and CaMKII were detected by gamma-(32)P substrate incorporation. The results showed that, compared with the sham operation group, the heart failure group exhibited reduced Ca(2+) re-uptake amount (P < 0.01) and the expression and activity of SERCA2a (P < 0.05 or P < 0.01), decreased expression of PLB and its phosphorylation status in sites of Ser(16) and Thr(17) (P < 0.05), increased expressions and activities of PKA and CaMKII (P < 0.05 or P < 0.01), and increased expression of PP1alpha (P < 0.05). These results suggest that the abnormal Ca(2+) re-uptake function in heart failure is related with reduced expression and activities of SERCA2a, as well as reduced expression of PLB and its phosphorylation status. Both PLB-Ser(16) and -Thr(17) may be involved in the regulation of myocardium SR calcium pump activity in heart failure. PMID- 25131792 TI - [Ox-LDL down-regulates expression of pigment epithelium-derived factor in human umbilical vein endothelial cells]. AB - Pigment epithelium-derived factor (PEDF) is a multifunctional protein with anti inflammatory, antioxidant and antithrombotic properties and plays a protective role against atherosclerosis (AS). The purpose of the present study is to explore the effects of oxidized low density lipoprotein (ox-LDL) on the expression of PEDF in cultured human umbilical vein endothelial cells (HUVECs). HUVECs were cultured and incubated with ox-LDL at different concentrations (6.25, 12.5, 25, 50, 100 and 150 mg/L) for 24 h. Apoptosis of endothelial cells were assayed by morphological staining and flow cytometry. The intracellular reactive oxygen species (ROS) levels were measured by flow cytometry. Cell viability was assayed by MTT assay. PEDF protein and mRNA expressions in HUVECs were analyzed by Western blot and quantitative real-time PCR, respectively. The results showed that ox-LDL significantly induced apoptosis, reduced cell viability, increased intracellular ROS levels and decreased the PEDF expression in HUVECs in a concentration-dependent manner. Ox-LDL at 50 mg/L obviously decreased the PEDF protein expression compared with control group (P < 0.05), whereas 25 mg/L ox-LDL already markedly reduced the PEDF mRNA expression (P < 0.05). In conclusion, the results suggest that ox-LDL down-regulates the PEDF expression through an increased ox-LDL-induced intracellular production of ROS. PMID- 25131793 TI - Sequencing approaches in cancer treatment. AB - Use of sequencing approaches is an important aspect in the field of cancer genomics, where next-generation sequencing has already been utilized for targeting oncogenes or tumour-suppressor genes, that can be sequenced in a short time period. Alterations such as point mutations, insertions/deletions, copy number alterations, chromosomal rearrangements and epigenetic changes are encountered in cancer cell genomes, and application of various NGS technologies in cancer research will encounter such modifications. Rapid advancement in technology has led to exponential growth in the field of genomic analysis. The $1000 Genome Project (in which the goal is to sequence an entire human genome for $1000), and deep sequencing techniques (which have greater accuracy and provide a more complete analysis of the genome), are examples of rapid advancements in the field of cancer genomics. In this mini review, we explore sequencing techniques, correlating their importance in cancer therapy and treatment. PMID- 25131794 TI - Costs and outcome of assertive community treatment (ACT) in a rural area in Denmark: 4-year register-based follow-up. AB - PURPOSE: Health economic evidence of assertive community treatment (ACT) in Denmark is limited. The aim of the study was to assess the costs and outcome of ACT among 174 patients with severe and persistent mental illness in a rural area of Denmark. METHODS: The study was based on a quasi-experimental design with a control group from the neighbouring region. Costs and retention in mental health services were analysed by using register data 1 year before and 4 years after inclusion in the study. Data on the use of supportive housing were available for the year before baseline and the subsequent 2 years only. RESULTS: Seventy eight percent of the patients receiving ACT were in contact with psychiatric services at the 4-year follow-up, while 69% of the patients in the control group had contact with psychiatric services (P < 0.17). Days in supportive housing were lower for the ACT group before baseline and remained so (dropping to zero) for the subsequent 2 years. Over 4 years, the mean total costs per patient in the group receiving ACT were DDK 493,442 (SE = 34,292). Excluding costs of supportive housing, the mean total costs per patient of the control group were DDK 537,218 (SE = 59,371), P < 0.53. If these costs are included, however, the mean total costs for the ACT group are unchanged, whereas costs for the control group rise to DDK 671,500 (SE = 73,671), P < 0.03. CONCLUSION: While ACT appears to have resulted in a significant reduction in costs for psychiatric hospitalizations, baseline differences in use of supportive housing make the effects of ACT on overall costs more ambiguous. At worst, however, overall costs did not increase. Given the generally acknowledged clinical benefits of ACT over standard outpatient care, the results support further dissemination of ACT in Denmark. PMID- 25131795 TI - Electronic monitoring of psychomotor activity as a supplementary objective measure of depression severity. AB - BACKGROUND: Rating scales used to assess the severity of depression e.g. the Hamilton Depression Rating Scale 17-item (HDRS-17) partly rely on the patient's subjective experience and reporting. Such subjective measures tend to have low reliability and adding objective measures to complement the assessment of depression severity would be a major step forward. AIMS: To investigate correlations between electronic monitoring of psychomotor activity and severity of depression according to HDRS-17. METHODS: A total of 36 patients with unipolar disorder (n = 18) or bipolar disorder (n = 18) and 31 healthy control persons aged 18-60 years were included. Psychomotor activity was measured using a combined heart rate and movement sensor device (Actiheart) for 3 consecutive days, 24 h a day. RESULTS: We found that sleeping heart rate (beats/min) correlated with HDRS-17 in both patients with unipolar disorder and bipolar disorder (unadjusted model: B = 0.46, 95% CI 0.037-0.89, P = 0.034). In contrast, correlations between activity energy expenditure (kJ/kg/day), cardio-respiratory fitness (mlO2/min/kg) and HDRS-17 were non-significant. CONCLUSIONS: These results suggest that measuring sleeping heart rate in non-experimental daily life could be an objective supplementary method to measure the severity of depression and perhaps indicate presence of insomnia. PMID- 25131796 TI - Stability and changes in metabolically healthy overweight or obesity and risk of future diabetes: Niigata wellness study. AB - OBJECTIVE: Stability and changes in obesity and metabolic health status from a baseline period and longitudinally investigated their impact on predicting future diabetes were assessed. METHODS: Studied were 27,478 Japanese individuals without diabetes. Metabolically healthy (MH) was indicated by having <=1 among impaired fasting glucose, hypertension, hypertriglyceridemia and low HDL cholesterol concentration. Metabolically abnormal (MA) was indicated by having >=2 of those metabolic abnormalities. A cut-off value of BMI 25.0 defined overweight or obesity (O) or normal weight (NW). Hazard ratio (HR) for diabetes for a 6-year period was investigated after changes in phenotypes were assessed during the previous 2 years. RESULTS: Compared with maintaining MH-NW, transitioning to MH-O from MH-NW resulted in a multivariate-adjusted HR of 1.96 (95% CI: 1.18, 3.25) for diabetes. With a stable MH-O the HR for diabetes was 2.59 (2.00, 3.34) while change from MH-O to MH-NW resulted in an HR of 1.30 (0.61, 2.76). Transitioning to MA-O from MH-O was associated with an HR of 7.09 (5.41, 9.30). With a stable MA-O the risk of diabetes was substantially elevated with an HR of 12.5 (10.5, 14.9). CONCLUSIONS: Examining the transitory nature of apparently benign or unhealthy obese phenotypes was effective for differentiating high-risk individuals for future diabetes. PMID- 25131798 TI - Disparate postoperative results in the first and second knees on simultaneous bilateral total knee arthroplasty. AB - We hypothesized that the circumstances of the two consecutive operations of a simultaneous bilateral total knee arthroplasty (TKA) are different, and could lead to different outcomes of overlapping bilateral TKAs. Both knees of 420 subjects were evaluated in the current study. In the second TKA, there were more incidence rates of outlier in mechanical femoro-tibial angle (16.2% vs. 9.0%), more blood loss (735 vs. 656 mL), and longer operation time (61, 58 minutes respectively), as compared to the first TKA, while no significant differences in clinical outcomes. In conclusion, there were no significant differences in the clinical outcomes even though few distinct outcomes due to different circumstances of the surgery. Awareness of these findings can help the continued success of bilateral TKA in an increasing patient population. PMID- 25131799 TI - Enhancing the performance of accelerated MRI through preservation of acquisition SNR: An "aliased" k-space approach. AB - PURPOSE: A method for preserving acquisition SNR through simultaneous acquisitions of distinct k-space phase encodes to enhance the performance of accelerated MRI is presented. THEORY AND METHODS: An excitation module comprising RF pulses and gradients is inserted into a sequence of choice to overlap and acquire distinct k-space phase encodes. This accelerates a scan as all phase encodes can now be acquired in a duration shorter than that of a typical scan. Next, this "aliased k-space" is restored during reconstruction using receiver sensitivity profiles. When the aliased k-space is also sub-sampled for additional acceleration, Parallel Imaging (PMRI) is applied first to synthesize the unacquired aliased samples. The synthesized samples are then used with the acquired samples in an iterative reconstruction to obtain the output. RESULTS: Depending on the sequence, acquisition SNR increased by 18-25% relative to PMRI or by 5% relative to the unaccelerated scan. This compensates for the SNR loss when the aliased k-space is sub-sampled for additional acceleration. With PMRI, the method could enable acceleration factors as high as 12 in 2D cartesian scans. CONCLUSION: A method for accelerating MRI scans through aliased k-space acquisitions and the feasibility of combining the same with PMRI for greater acceleration has been demonstrated. Magn Reson Med 74:150-161, 2015. (c) 2014 Wiley Periodicals, Inc. PMID- 25131797 TI - p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells. AB - Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E overexpressing cancer cells by positive regulation of p21. PMID- 25131800 TI - Phenolic compounds in grains, sprouts and wheatgrass of hulled and non-hulled wheat species. AB - BACKGROUND: The use of sprouts and young plantlets in human nutrition is increasing because they often contain phytochemicals and other high value nutrients. This is also the case for wheat, although there is no literature for hulled wheat species. Thus we determined total polyphenols, phenolic acids (PAs), fibre and minerals in grains, 5-day-old sprouts and 12-day-old wheatgrass of einkorn (cv. Monlis), emmer (cvs Augeo, Rosso Rubino, Zefiro), spelt (cvs Pietro, Giuseppe), durum wheat (cv. Creso) and soft wheat (cv. Orso). RESULTS: Grains of einkorn and emmer contained twice bound PAs as compared to soft and durum wheat and spelt, with p-coumaric acid accounting for about 50% of total bound PAs. In wheatgrass, differences between species for bound PAs decreased due to a decrease in einkorn and emmer and an increase in soft and durum wheat. In all species, total phenols and free PAs increased passing from grains to sprouts and wheatgrass. Neutral and acid detergent fibre content increased with sprouting only in einkorn and emmer. CONCLUSION: Our evidence suggests that the grains of einkorn and emmer and the sprouts and wheatgrass of all Triticum species might potentially be valuable for the development of functional foods. PMID- 25131801 TI - CD4 trajectory adjusting for dropout among HIV-positive patients receiving combination antiretroviral therapy in an East African HIV care centre. AB - OBJECTIVE: Estimates of CD4 response to antiretroviral therapy (ART) obtained by averaging data from patients in care, overestimate population CD4 response and treatment program effectiveness because they do not consider data from patients who are deceased or not in care. We use mathematical methods to assess and adjust for this bias based on patient characteristics. DESIGN: We examined data from 25,261 HIV-positive patients from the East Africa IeDEA Consortium. METHODS: We used inverse probability of censoring weighting (IPCW) to represent patients not in care by patients in care with similar characteristics. We address two questions: What would the median CD4 be "had everyone starting ART remained on observation?" and "were everyone starting ART maintained on treatment?" RESULTS: Routine CD4 count estimates were higher than adjusted estimates even under the best-case scenario of maintaining all patients on treatment. Two years after starting ART, differences between estimates diverged from 30 cells/uL, assuming similar mortality and treatment access among dropouts as patients in care, to over 100 cells/uL assuming 20% lower survival and 50% lower treatment access among dropouts. When considering only patients in care, the proportion of patients with CD4 above 350 cells/uL was 50% adjusted to below 30% when accounting for patients not in care. One-year mortality diverged 6-14% from the naive estimates depending on assumptions about access to care among lost patients. CONCLUSIONS: Ignoring mortality and loss to care results in over estimation of ART response for patients starting treatment and exaggerates the efficacy of treatment programs administering it. PMID- 25131803 TI - The health perspectives of Australian adolescents from same-sex parent families: a mixed methods study. AB - BACKGROUND: Research involving adolescents from same-sex parent families provides an important contribution to the evidence base on their health, well-being and the impact of stigma. To date reports on the perspectives of adolescents with same-sex attracted parents have been limited. This study aimed to describe the multidimensional experiences of physical, mental and social well-being of adolescents living in this context. METHODS: A mixed methods study of adolescents with same-sex attracted parents comprising of an adolescent-report survey of 10- to 17-year-olds and family interviews with adolescents and their parents. Data were collected in 2012 and 2013 as part of the Australian Study of Child Health in Same-Sex Families. RESULTS: The findings from qualitative interviews with seven adolescents and responses to an open-ended survey question (n = 16) suggest four themes: perceptions of normality, positive concepts of health, spheres of life (including family, friends and community) and avoiding negativity. The quantitative sample of adolescents with same-sex attracted parents (n = 35) reported higher scores than population normative data on the dimensions general health and family activities within the Child Health Questionnaire (CHQ) as well as higher on the peer problems scale on the Strengths and Difficulties Questionnaire (SDQ). Perceived stigma correlates with lower health and well-being overall. CONCLUSIONS: Positive health outcomes are informed by the ways adolescents conceptualize health and how they construct their spheres of life. Peer relationships, and community perspectives of same-sex families, inform perceived stigma and its correlation with poorer health and well-being. Although adolescents see their families as essentially normal they are negatively affected by external societal stigma. PMID- 25131802 TI - Initial solid tumor testing (stage 1) of AZD1480, an inhibitor of Janus kinases 1 and 2 by the pediatric preclinical testing program. AB - BACKGROUND: AZD1480 is an ATP competitive inhibitor of Janus kinases 1 and 2 (JAK1, 2) that has been shown to inhibit the growth of solid tumor models. This agent was selected for testing the putative role of JAK/STAT signaling in the standard PPTP solid tumor models. PROCEDURES: AZD1480 was tested against the PPTP in vitro cell line panel at concentrations from 1.0 nM to 10 MUM and against the PPTP in vivo solid tumor xenograft panels at (60 mg/kg once daily (SID) * 5) for three consecutive weeks. Additional studies evaluated 5 to 20 mg/kg BID * 5 with SID dosing at 7-30 mg/kg at weekends for three consecutive weeks. RESULTS: In vitro the median relative IC50 (rIC50 ) for the PPTP cell lines was 1.5 uM, with a range from 0.3 uM to 5.9 uM. The two cell lines with rIC50 values of 0.3 uM both had ALK activating genomic alterations. AZD1480 demonstrated statistically significant differences (P < 0.05) in EFS distribution compared to control in 89% of the solid tumor xenografts. AZD1480 induced intermediate (EFS T/C > 2) or high level growth inhibition in 15 of 30 (50%) solid tumor xenografts. Tumor regressions were observed in three of six Wilms tumor models at doses that induced inhibition of Stat3(Y705) phosphorylation. CONCLUSIONS: AZD1480 demonstrated significant tumor growth inhibition against most PPTP solid tumor xenografts, similar to that observed for antiangiogenic agents tested by the PPTP. Tumor regressing activity was noted for Wilms tumor xenografts. PMID- 25131804 TI - Hydranencephaly in a newborn with a FLVCR2 mutation and prenatal exposure to cocaine. AB - BACKGROUND: Hydranencephaly is a relatively rare but severe structural brain abnormality that often results in perinatal death. Although several factors including infection and multiple births have been reported to be associated with this birth defect, the underlying etiology is not well understood. Recently, FLVCR2 gene mutations have been implicated in a subset of hydranencephaly cases, following an autosomal recessive pattern of inheritance. CASE: We report a male infant with hydranencephaly found to have a previously unreported six amino acid deletion in one copy of the FLVCR2 gene following a pregnancy complicated by poor prenatal care and maternal cocaine use. Although our patient currently presents with developmental delays, he is showing progress and gaining some skills. CONCLUSION: We discuss the possibility of a synergistic effect between the FLVCR2 genetic mutation and environmental cocaine exposure, creating a susceptible brain, as an explanation for this infant's phenotype. This case demonstrates the potential clinical utility of testing for mutations in FLVCR2 for patients with hydranencephaly after other possible etiologies, such as congenital infection, have been reasonably eliminated. Current literature on FLVCR2 is relatively sparse; identifying additional patients with similar mutations will aid in defining the clinical significance of a gene mutation and the contribution to the etiology of hydranencephaly. PMID- 25131805 TI - Hepatic fungal infection in a young beagle with unrecognised hereditary cobalamin deficiency (Imerslund-Grasbeck syndrome). AB - A 12-month-old beagle presented for anorexia, pyrexia and vomiting. The dog had been treated intermittently with antibiotics and corticosteroids for inappetence and lethargy since five months of age. Previous laboratory abnormalities included macrocytosis and neutropenia. At presentation, the dog was lethargic, febrile and thin. Laboratory examination findings included anaemia, a left shift, thrombocytopenia, hypoglycaemia and hyperbilirubinaemia. Multiple, small, hypoechoic, round hepatic lesions were observed on abdominal ultrasound. Cytological examination of hepatic fine needle aspirates revealed a fungal infection and associated pyogranulomatous inflammation. The dog's general condition deteriorated despite supportive measures and treatment with fluconazole, and owners opted for euthanasia before hypocobalaminaemia was identified. Subsequent genomic analysis revealed a CUBN:c.786delC mutation in a homozygous state, confirming hereditary cobalamin malabsorption (Imerslund Grasbeck syndrome). Similar to human infants, dogs with Imerslund-Grasbeck syndrome may rarely be presented for infectious diseases, distracting focus from the underlying primary disorder. PMID- 25131808 TI - Discovery of natural infection by Metagonimus hakubaensis Shimazu, 1999 (Trematoda: Heterophyidae) in Japanese water shrews (Chimarrogale platycephala) in Japan. AB - A total of 611 preserved adult Metagonimus spp. specimens recovered from 32 of 53 Japanese water shrews (Chimarrogale platycephala) that had previously been collected in Aomori Prefecture between June 1994 and August 1996, were examined in this study. Morphological examination revealed that 603 of these flukes were identical to M. hakubaensis Shimazu, 1999, and that the others were M. takahashii Suzuki, 1930 (n=4), M. otsurui Saito et Shimizu, 1968 (n=2), and M. miyatai Saito et al., 1997 (n=2). Each of the 32 Japanese water shrews infected with M. hakubaensis contained between 1 and 83 flukes. This is the first record of the natural final host for M. hakubaensis, since this fluke species was described. PMID- 25131807 TI - G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent. AB - G-CSF was among the first cytokines to be identified and rapidly transitioned into clinical medicine. Initially used to promote the production of neutrophils in patients with chemotherapy-induced neutropenia it helped to revolutionize the delivery of cancer therapy. Its ability to mobilize hematopoietic stem cells from the bone marrow into the blood was subsequently exploited, changing the face of hematopoietic stem cell transplantation. Today the knowledge gained in unraveling the mechanisms of stem cell mobilization by G-CSF is being explored as a means to increase chemosensitivity in hematological malignancies. This review provides a brief history of G-CSF and then focuses on recent advances in our understanding of G-CSF-induced stem cell mobilization and the potential clinical application of this knowledge in chemo-sensitization. PMID- 25131806 TI - Personality assessment inventory internalizing and externalizing structure in veterans with posttraumatic stress disorder: associations with aggression. AB - Posttraumatic stress disorder (PTSD) is associated with aggressive behavior in veterans, and difficulty controlling aggressive urges has been identified as a primary postdeployment readjustment concern. Yet only a fraction of veterans with PTSD commit violent acts. The goals of this study were to (1) examine the higher order factor structure of Personality Assessment Inventory (PAI) scales in a sample of U.S. military veterans seeking treatment for PTSD; and (2) to evaluate the incremental validity of higher-order latent factors of the PAI over PTSD symptom severity in modeling aggression. The study sample included male U.S. Vietnam (n = 433) and Iraq/Afghanistan (n = 165) veterans who were seeking treatment for PTSD at an outpatient Veterans Affairs (VA) clinic. Measures included the Clinician Administered PTSD Scale, the PAI, and the Conflict Tactics Scale. The sample was randomly split into two equal subsamples (n's = 299) to allow for cross-validation of statistically derived factors. Parallel analysis, variable clustering analysis, and confirmatory factor analyses were used to evaluate the factor structure, and regression was used to examine the association of factor scores with self-reports of aggression over the past year. Three factors were identified: internalizing, externalizing, and substance abuse. Externalizing explained unique variance in aggression beyond PTSD symptom severity and demographic factors, while internalizing and substance abuse did not. Service era was unrelated to reports of aggression. The constructs of internalizing versus externalizing dimensions of PTSD may have utility in identifying characteristics of combat veterans in the greatest need of treatment to help manage aggressive urges. PMID- 25131809 TI - Phylogenetic analysis of fowl adenoviruses isolated from chickens with gizzard erosion in Japan. AB - Thirty-four fowl adenoviruses (FAdVs) isolated from chickens with gizzard erosion (GE) from 1999 to 2010 were characterized phylogenetically together with foreign isolates. The phylogenetic analysis based on part of the hexon gene classified these 34 FAdV isolates into 3 groups: FAdV-1, -8a and 8b, thereby suggesting that FAdVs associated with GEs in chickens are diverse. All 30 FAdV-1 isolates were genetically identical, and they were also identical with FAdV-1 isolates from GEs in chickens in European countries (Germany, Poland, Austria, Hungary and Italy). Thus, the same type of FAdV-1 has been associated with outbreaks of GE in Japanese chickens for the past 10 years, which may have spread from a common ancestor, although the epidemiological relationship is unknown. PMID- 25131810 TI - Overexpression of EZH2 associates with a poor prognosis in chronic lymphocytic leukemia. AB - EZH2, a histone methyltransferase, is overexpressed in several human tumors, but whether it exerts any impact in chronic lymphocytic leukemia (CLL) remains unknown. We used real time PCR to investigate the expression profile of EZH1 and EZH2 in 59 CLL patients, 10 samples of purified B-cells from healthy donors and 12 normal adult tissues. EZH2 was overexpressed in CLL patients and correlates with high white blood cell count, ZAP-70 expression and chromosomal abnormalities. EHZ1 expression does not correlate with CLL progression. EZH2 overexpression is related to a poor prognosis of CLL and could be a useful tool to assess its aggressiveness. PMID- 25131812 TI - Strategies addressing barriers to clinical trial enrollment of underrepresented populations: a systematic review. AB - BACKGROUND: Underrepresentation of racial and ethnic minorities in clinical trials remains a reality while they have disproportionately higher rates of health disparities. OBJECTIVE: The purpose of this study was to identify successful community-engaged interventions that included health care providers as a key strategy in addressing barriers to clinical trial enrollment of underrepresented patients. DESIGN: A systematic review of the literature on interventions addressing enrollment barriers to clinical trials for racial and ethnic minorities was performed in Ovid MEDLINE, EBSCO Megafile, and EBSCO CINAHL. The systematic review identified 360 studies, and 20 were selected using the inclusion criteria. An iterative process extracted information from the eligible studies. RESULTS: The 20 selected studies were analyzed and then grouped by first author, nature of the clinical research initiative, priority populations, key strategies, and study outcomes. Nine of the studies addressed cancer clinical trials and 11 related to chronic medical conditions, including diabetes, hypertension management, and chronic kidney disease. The key strategies employed were categorized according to their presumed impact on barriers incurred at distinct steps in study recruitment: clinical trial awareness, opportunity to participate, and acceptance of enrollment. The strategies were further categorized by whether they would address barriers associated with minority perceptions of the research process and barriers related to how studies were designed and implemented. CONCLUSION: Multiple and flexible strategies targeting providers and participants at provider sites and within communities might be needed to enroll underrepresented populations into clinical trials. PMID- 25131813 TI - ClereMed: Lessons Learned From a Pilot Study of a Mobile Screening Tool to Identify and Support Adults Who Have Difficulty With Medication Labels. AB - BACKGROUND: In order to take medications safely and effectively, individuals need to be able to see, read, and understand the medication labels. However, one-half of medication labels are currently misunderstood, often because of low literacy, low vision, and cognitive impairment. We sought to design a mobile tool termed ClereMed that could rapidly screen for adults who have difficulty reading or understanding their medication labels. OBJECTIVE: The aim of this study was to build the ClereMed prototype; to determine the usability of the prototype with adults 55 and over; to assess its accuracy for identifying adults with low functional reading ability, poor ability on a real-life pill-sorting task, and low cognition; and to assess the acceptability of a touchscreen device with older adults with age-related changes to vision and cognition. METHODS: This pilot study enrolled adults (>=55 years) who were recruited through pharmacies, retirement residences, and a low-vision optometry clinic. ClereMed is a hypertext markup language (HTML)-5 prototype app that simulates medication taking using an iPad, and also provides information on how to improve the accessibility of prescription labels. A paper-based questionnaire included questions on participant demographics, computer literacy, and the Systems Usability Scale (SUS). Cognition was assessed using the Montreal Cognitive Assessment tool, and functional reading ability was measured using the MNRead Acuity Chart. Simulation results were compared with a real-life, medication-taking exercise using prescription vials, tablets, and pillboxes. RESULTS: The 47 participants had a mean age of 76 (SD 11) years and 60% (28/47) were female. Of the participants, 32% (15/47) did not own a computer or touchscreen device. The mean SUS score was 76/100. ClereMed correctly identified 72% (5/7) of participants with functional reading difficulty, and 63% (5/8) who failed a real-life pill-sorting task, but only 21% (6/28) of participants with cognitive impairment. Participants who owned a computer or touchscreen completed ClereMed in a mean time of 26 (SD 16) seconds, compared with 52 (SD 34) seconds for those who do not own a device (P<.001). Those who had difficulty, struggled with screen glare, button activation, and the "drag and drop" function. CONCLUSIONS: ClereMed was well accepted by older participants, but it was only moderately accurate for reading ability and not for mild cognitive impairment. Future versions may be most useful as part of a larger medication assessment or as a tool to help family members and caregivers identify individuals with impaired functional reading ability. Future research is needed to improve the sensitivity for measuring cognitive impairment and on the feasibility of implementing a mobile app into pharmacy workflow. PMID- 25131814 TI - In memoriam: Geoffrey Louis Zubay, 1931-2014. Pioneer in cell-free gene expression studies and molecular genetics. PMID- 25131815 TI - Holliday junction processing enzymes as guardians of genome stability. AB - Holliday junctions (HJs) are four-stranded DNA intermediates that arise during the recombinational repair of DNA double-strand breaks (DSBs). Their timely removal is crucial for faithful chromosome segregation and genome stability. In mammalian cells, HJs are processed by the BTR (BLM-topoisomerase IIIalpha-RMI1 RMI2) complex, the SLX-MUS (SLX1-SLX4-MUS81-EME1) complex, and the GEN1 resolvase. Recent studies have linked the deficiency of one or more of these enzymes to perturbed DNA replication, impaired crosslink repair, chromosomal instability, and defective mitoses, coupled with the transmission of widespread DNA damage and high levels of mortality. We review these key advances and how they have cemented the status of HJ-processing enzymes as guardians of genome integrity and viability in mammalian cells. PMID- 25131811 TI - Grip it and rip it: structural mechanisms of DNA helicase substrate binding and unwinding. AB - Maintenance and faithful transmission of genomic information depends on the efficient execution of numerous DNA replication, recombination, and repair pathways. Many of the enzymes that catalyze steps within these pathways require access to sequence information that is buried in the interior of the DNA double helix, which makes DNA unwinding an essential cellular reaction. The unwinding process is mediated by specialized molecular motors called DNA helicases that couple the chemical energy derived from nucleoside triphosphate hydrolysis to the otherwise non-spontaneous unwinding reaction. An impressive number of high resolution helicase structures are now available that, together with equally important mechanistic studies, have begun to define the features that allow this class of enzymes to function as molecular motors. In this review, we explore the structural features within DNA helicases that are used to bind and unwind DNA. We focus in particular on "aromatic-rich loops" that allow some helicases to couple single-stranded DNA binding to ATP hydrolysis and "wedge/pin" elements that provide mechanical tools for DNA strand separation when connected to translocating motor domains. PMID- 25131816 TI - Import routes and nuclear functions of Argonaute and other small RNA-silencing proteins. AB - Small RNAs are important regulators of gene expression in many different organisms. Nuclear and cytoplasmic biogenesis enzymes generate functional small RNAs from double-stranded (ds) or single-stranded (ss) RNA precursors, and mature small RNAs are loaded into Argonaute proteins. In the cytoplasm, small RNAs guide Argonaute proteins to complementary RNAs leading to cleavage of these targets, translational silencing, or mRNA decay. In the nucleus Argonaute proteins engage in transcriptional silencing processes such as epigenetic silencing of repetitive elements at the chromatin level. During the past few years many novel functions of small RNA-guided gene silencing proteins in the nucleus have been reported. However, their specific import routes are largely unknown. In this review we summarize the current knowledge on nuclear transport routes that Argonaute and other RNA-silencing proteins take to carry out their various functions in the nucleus. PMID- 25131818 TI - An unusual case of preexcitation treated with a pacemaker. PMID- 25131817 TI - Prognostic value of cyclooxygenase-2 gene polymorphisms in advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy. AB - AIM: Cyclooxygenase-2 (COX-2) plays an important role in cell apoptosis, angiogenesis and tumor invasion, and over-expression of COX-2 is associated with tumor development and occurrence. The aim of this study is to investigate the association between COX-2 polymorphisms and clinical outcomes in advanced non small cell lung cancer (NSCLC) patients treated with first-line platinum-based chemotherapy. METHODS: A total of 190 patients with IIIB or IV NSCLC who received platinum-based chemotherapy were recruited in this study. Four functional COX-2 polymorphisms, including rs689465, rs689466, rs3218625 and rs20417, were genotyped by PCR-based restriction fragment length polymorphism methods. Kaplan Meier methods were used to compare survival by different genotypes. Cox proportional hazard models were used to identify independently significant variables. RESULTS: The rs689465 AA genotype was significantly associated with longer overall survival (OS) (13.0 months vs 8.8 months, P = 0.019 for log-rank test; hazard ratio [HR] 0.624; 95% confidence internal [CI] 0.418-0.931) and progression-free survival (5.3 months vs 4.0 months, P = 0.018 for log-rank test; HR 0.627; 95% CI 0.421-0.934) compared with AG or GG genotype, especially in patients with adenocarcinoma (P = 0.002), performance status of 1 (P = 0.009) and stage IV disease (P = 0.012), and treated with gemcitabine-based chemotherapy (P = 0.012). Multivariate regression analysis showed that COX-2 rs689465 polymorphism had a significantly independent prognostic value for OS (P = 0.017, HR = 1.637, 95% CI = 1.093-2.453). CONCLUSION: Our study suggested that rs689465 polymorphism could be a prognostic biomarker for advanced NSCLC patients treated with first-line platinum-based chemotherapy. PMID- 25131819 TI - Heart failure in adult congenital heart disease. AB - OPINION STATEMENT: Adult congenital heart disease (ACHD) patients represent a special population in modern cardiology: though their numbers are growing, and they represent a high-resource utilization subgroup, a robust evidence-base of randomized trials is lacking. Much of the standard therapy is adapted from the treatment of ischemic and idiopathic left ventricle systolic failure, with a small, but growing body of evidence on medical therapy in select ACHD diagnoses. At our institution, for instance, there is a long tradition of using angiotensin antagonists in patients with a systemic right ventricle to prevent deleterious remodeling. The effects of beta-blockers on functional class in ACHD are yet unproven, but there is promising data on pulmonary vasodilators. Control of coronary risk factors and aerobic exercise should be considered for all. Prevention of arrhythmias is important, and multi-site pacing is an emerging therapy. New prognostic tools including natriuretic peptides and CPET are increasingly used to guide earlier initiation of these therapies. PMID- 25131820 TI - Perioperative physiology and pharmacology in the obese small animal patient. AB - OBJECTIVE: To review the available literature concerning the physiologic and pharmacologic alterations induced by obesity in canine and feline patients and their relevance to perioperative care. STUDY DESIGN: Literature review. DATABASES: PubMed, CAB, Web of Science. CONCLUSIONS: Obesity of cats and dogs is a chronic inflammatory condition that is increasingly prevalent. Similar to the situation in humans, small animal obesity may be associated with changes in endocrine, respiratory, and cardiovascular function. In addition, alteration of body composition in obesity can affect pharmacokinetic variables. Modifications in perioperative care may need to be made for obese dogs and cats, including attention to respiratory and cardiovascular supportive care and drug dose adjustments. PMID- 25131821 TI - Microscopic and ultrastructural features in Wolcott-Rallison syndrome, a permanent neonatal diabetes mellitus: about two autopsy cases. AB - BACKGROUND: Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple bone dysplasia, hepatic dysfunction, and growth retardation. All clinical manifestations result from gene mutations encoding pancreatic endoplasmic reticulum eIF2 alpha kinase (PERK), an endoplasmic reticulum transmembrane protein that plays a role in the unfolded protein response. Histological and ultrastructural lesions of bone and pancreas have been described in animal models and WRS patients. However, histological and ultrastructural findings of other organs, especially of the liver, are lacking. METHODS: Autopsy specimens from two pediatric patients with WRS were analyzed. An immunohistochemical study was performed on the pancreas. An ultrastructural study was realized from samples of liver, pancreas, kidney, and myocardium. Our findings were compared with those of the literature and correlated with the molecular data. RESULTS: Hepatocytes and pancreatic exocrine cells exhibited very peculiar features of necrosis suggestive of secondary changes because of endoplasmic reticulum overload. Steatosis occurred in renal tubular cells, hepatocytes, and myocardial fibers. Abnormal mitochondria were noted in renal and myocardial fibers. Pancreas islets were characterized by a marked reduction in the number of insulin-secreting beta cells. CONCLUSIONS: The histological and ultrastructural features that occur in WRS are directly or indirectly linked to endoplasmic reticulum (ER) dysfunction and can explain the peculiar phenotype of this syndrome. PMID- 25131822 TI - Serological characterization of occult hepatitis B virus infection among blood donors in India. AB - INTRODUCTION: Discovery of hepatitis B infections characterized by the presence of viral genome without detectable HBsAg (Occult Hepatitis; OBI) has initiated a considerable amount of research in this regard. Our study is a serological and molecular characterization of OBI among the donors who donated at our blood bank during the study period. MATERIAL AND METHOD: During the study period HBsAg ELISA non reactive ID-NAT reactive donors samples were screened for presence of antibody against HBc, HBs and HBe. Molecular analysis of these NAT yield samples was undertaken for detection of the viral load and genotyping. RESULT: We studied 28,134 HBsAg ELISA non reactive donor samples. On testing them with ID-NAT, HBV DNA was detected in 25 samples. Eighteen samples out of these 25 NAT yield were further worked up. The 66.6% of the NAT yield samples (12 out of 18) were reactive for antibody against HBc. The 25% (3 out of 12) of these NAT yield samples having antibody against core antigen also had antibody against HBs. The 27.7% (5 out of 18) of NAT yield detected by ID-NAT did not have any detectable serological marker in blood. Four out of 12 core antibody positive NAT yield samples had genotype A HBV infection. CONCLUSION: As per our study molecular detection of HBV DNA by ID-NAT, we were able to analyze 18 HBV NAT yield cases among 28,134 HBsAg ELISA non reactive donors. Out of 18, 12 donors were OBI whereas the rest (6) were in window period (WP yield) of HBV infection. One out of every 3.6 NAT yield detected by ID-NAT was non reactive for all serological markers. PMID- 25131823 TI - Diffusion tensor tractography in hypothyroidism and its correlation with memory function. AB - Diffusion tensor tractography (DTT) was performed to determine the microstructural changes in the white matter fibre tracts of hypothyroid patients compared to controls and to correlate these changes with memory dysfunction scores. DTT and Postgraduate Institute Memory Scale test were performed in eight hypothyroid patients and eight healthy controls. Diffusion tensor imaging (DTI) measures [fractional anisotropy (FA) and mean diffusivity (MD)] from all of the major cerebral tracts were calculated and a comparison was made between the patient group and controls. Pearson's correlation was performed between Memory Dysfunction score and DTI measures. Significant changes in DTI measures were observed in various white matter fibre tracts in hypothyroid patients compared to controls. In hypothyroid patients, an inverse correlation of Memory Dysfunction score with FA was observed in the right and left inferior fronto-occipital fasciculus, whereas a positive correlation with MD was observed in the right anterior thalamic radiation among all white matter tracts. These findings suggest that microstructural changes in white matter fibres may contribute to the underlying dysfunction in memory in hypothyroid patients. PMID- 25131824 TI - The 2014 ACR Commission on Human Resources workforce survey. AB - BACKGROUND: The ACR Commission on Human Resources conducts an annual electronic survey during the first quarter of the year to better understand the present workforce scenario for radiologists and allied health professionals. METHODS: The Practice of Radiology Environment Database is used to identify group leaders who are asked to complete an electronic survey developed by the Commission on Human Resources. The survey asked 1,936 group leaders or their designates to report the number of radiologists currently employed or supervised, the number hired in 2013, and the number they plan to hire in 2014 and 2017. The leaders were asked to report the subspecialty area that was used as the main reason for hiring each physician. RESULTS: The 22% response rate corresponds to 35% of all practicing radiologists in the United States. The 2014 survey demonstrated that 78% of the workforce is male and 22% is female and that 87% of the workforce works full time. Fifty-three percent of the current workforce is in private practice and 47% in varying forms of employment. The current workforce consists of 18% general radiologists and 82% subspecialists. In 2013, 1,069 radiologists were hired. In 2014, 1,114 job opportunities are projected, and 1,131 estimated jobs are forecast for 2017. CONCLUSIONS: Job opportunities for radiologists in 2014 remain similar to those in 2013 and close to the numbers of residents completing training programs in diagnostic radiology. Job opportunities remain available but may not necessarily be in the subspecialty, geographic area, or type of practice an individual most desires. PMID- 25131825 TI - Radiologist manpower considerations and Imaging 3.0: effort planning for value based imaging. AB - Our specialty is seeking to establish the value of imaging in the longitudinal patient-care continuum. We recognize the need to assess the value of our contributions rather than concentrating primarily on generating revenue. This recent focus is a result of both increased cost-containment efforts and regulatory demands. Imaging 3.0 is a value-based perspective that intends to describe and facilitate value-based imaging. Imaging 3.0 includes a broad set of initiatives addressing the visibility of radiologists, and emphasizing quality and safety oversight by radiologists, which are new directions of focus for us. Imaging 3.0 also addresses subspecialty imaging and off-hours imaging, which are existing areas of practice that are emblematic of inconsistent service delivery across all hours. Looking to the future, Imaging 3.0 describes how imaging services could be integrated into the framework of accountable care organizations. Although all these efforts may be essential, they necessitate manpower expenditures, and these efforts are not directly covered by revenue. If we recognize the urgency of need in developing these concepts, we can justify the manpower and staffing expenditures each organization is willing to shoulder in reaching Imaging 3.0. PMID- 25131826 TI - The importance of having zinc during in vitro maturation of cattle cumulus-oocyte complex: role of cumulus cells. AB - The aim of this study was to investigate the influence of zinc (Zn) on the health of cumulus-oocyte complex (COC) during in vitro maturation (IVM). Experiments were designed to evaluate the effect of Zn added to IVM medium on: DNA integrity, apoptosis, cumulus expansion and superoxide dismutase (SOD) activity of cumulus cells (CC). Also, role of CC on Zn transport during IVM was evaluated on oocyte developmental capacity. DNA damage and early apoptosis were higher in CC matured with 0 MUg/ml Zn compared with 0.7, 1.1 and 1.5 MUg/ml Zn (p < 0.05). Cumulus expansion did not show differences in COC matured with or without Zn supplementation (p > 0.05). Superoxide dismutase activity was higher in COC matured with 1.5 MUg/ml Zn than with 0 MUg/ml Zn (p < 0.05). Cleavage and blastocyst rates were recorded after IVM in three maturation systems: intact COCs, denuded oocytes with cumulus cells monolayer (DO + CC) and denuded oocytes (DO). Cleavage rates were similar when COC, DO + CC or DO were matured with 1.5 MUg/ml Zn compared with control group (p > 0.05). Blastocyst rates were significantly higher in COC than in DO + CC and DO with the addition of 1.5 MUg/ml Zn during IVM (p < 0.01). Blastocyst quality was enhanced in COC and DO + CC compared with DO when Zn was added to IVM medium (p < 0.001). The results of this study indicate that Zn supplementation to IVM medium (i) decreased DNA damage and apoptosis in CC; (ii) increased SOD activity in CC; (iii) did not modify cumulus expansion and cleavage rates after in vitro fertilization; (iv) improved subsequent embryo development up to blastocyst stage; and (v) enhanced blastocyst quality when CC were present either in intact COC or in coculture during IVM. PMID- 25131827 TI - Vascular stiffness is a biomarker of global cardiovascular risk. PMID- 25131828 TI - Shared and nonshared neural networks of cognitive and affective theory-of-mind: a neuroimaging study using cartoon picture stories. AB - Theory of mind (ToM) refers to the ability to represent one's own and others' cognitive and affective mental states. Recent imaging studies have aimed to disentangle the neural networks involved in cognitive as opposed to affective ToM, based on clinical observations that the two can functionally dissociate. Due to large differences in stimulus material and task complexity findings are, however, inconclusive. Here, we investigated the neural correlates of cognitive and affective ToM in psychologically healthy male participants (n = 39) using functional brain imaging, whereby the same set of stimuli was presented for all conditions (affective, cognitive and control), but associated with different questions prompting either a cognitive or affective ToM inference. Direct contrasts of cognitive versus affective ToM showed that cognitive ToM recruited the precuneus and cuneus, as well as regions in the temporal lobes bilaterally. Affective ToM, in contrast, involved a neural network comprising prefrontal cortical structures, as well as smaller regions in the posterior cingulate cortex and the basal ganglia. Notably, these results were complemented by a multivariate pattern analysis (leave one study subject out), yielding a classifier with an accuracy rate of more than 85% in distinguishing between the two ToM-conditions. The regions contributing most to successful classification corresponded to those found in the univariate analyses. The study contributes to the differentiation of neural patterns involved in the representation of cognitive and affective mental states of others. PMID- 25131829 TI - Lentiviral-mediated silencing of glial fibrillary acidic protein and vimentin promotes anatomical plasticity and functional recovery after spinal cord injury. AB - In spinal cord injury (SCI), absence of functional recovery and lack of spontaneous axonal regeneration are attributed, among other factors, to the formation of a glial scar that forms both physical and chemical barriers. The glial scar is composed mainly of reactive astrocytes that overexpress two intermediate filament proteins, glial fibrillary acidic protein (GFAP) and vimentin (VIM). To promote regeneration and sprouting of spared axons after spinal cord trauma and with the objective of translation to clinics, we designed an original in vivo gene transfer strategy to reduce glial scar formation after SCI, based on the RNA interference (RNAi)-mediated inhibition of GFAP and VIM. We first show that direct injection of lentiviral vectors expressing short hairpin RNA (shRNA) against GFAP and VIM in a mouse model of SCI allows efficient and specific targeting of astrocytes. We then demonstrate that the lentiviral mediated and stable expression of shGFAP and shVIM leads to a strong reduction of astrogliosis, improves functional motor recovery, and promotes axonal regrowth and sprouting of spared axons. This study thus examplifies how the nonneuronal environment might be a major target within the lesioned central nervous system to promote axonal regeneration (and sprouting) and validates the use of lentiviral mediated RNAi in SCI. PMID- 25131831 TI - Massive schizophrenia genomics study offers new drug directions. PMID- 25131832 TI - The CROWN Initiative: Journal editors invite researchers to develop core outcomes in women's health. PMID- 25131834 TI - Identification of a novel mutation in the polymerase delta 1 (POLD1) gene in a lipodystrophic patient affected by mandibular hypoplasia, deafness, progeroid features (MDPL) syndrome. AB - OBJECTIVE: Progressive lipodystrophy is one of the major features of the rare MDPL syndrome. Until now, 9 patients affected by this syndrome have been described and a recent study identified in 4 of them an in-frame deletion (Ser605del) of a single codon in the POLD1 gene. Sequence alterations of the POLD1 gene at different sites have been previously reported in human colorectal and endometrial carcinomas. MATERIALS/METHODS: A 48-year-old woman was admitted to our department for the assessment of a previously diagnosed lipodystrophy. She did not report a family history of diabetes or other metabolic disorders. Hypertriglyceridemia was diagnosed incidentally when she was 25years old. At that time she was also diagnosed with sensorineural bilateral hearing loss. At physical examination she presented lipoatrophy affecting nearly the entire body, mandibular hypoplasia, bird-like face, beaked nose, progeroid facial features, with crowded teeth, small mouth and uvula. Abdominal ultrasound showed hepatomegaly and hepatosteatosis. Fat mass index measured with DXA was 4.59kg/m(2), indicating a fat deficit; the oral glucose tolerance test showed an impaired glucose tolerance. RESULTS: Sequence analysis of the entire coding region of the POLD1 gene, disclosed a novel heterozygous mutation in exon 13 (R507C). CONCLUSION: The MDPL patient herein described harbors a novel mutation in the exonuclease domain of POLD1. This new variant provides further evidence for a role of POLD1 in the pathogenesis of MDPL. The mechanisms that link changes at various sites of the protein with different diseases remain to be clarified. PMID- 25131835 TI - Denosumab and osteonecrosis of the jaws - the pharmacology, pathogenesis and a report of two cases. AB - Denosumab (Amgen, Thousand Oaks, California, USA) is a new bone antiresorptive agent used in patients with osteoporosis or metastatic cancer to the bones. As with the bisphosphonates that are used as antiresorptive medications, denosumab has been associated with osteonecrosis of the jaws (ONJ). Over the past two years there has been an increase in the literature describing ONJ in patients receiving agents such as denosumab. Due to promising study results that demonstrate the effectiveness of denosumab in avoiding skeletal complications related to osteoporosis and metastatic bone disease, more patients will receive denosumab in the future. It is reported that this has the potential to become a comparable challenge to bisphosphonate related osteonecrosis of the jaws (BRONJ) for clinicians. This article describes the management of two patients that developed ONJ while receiving denosumab, reviews the incidence of ONJ associated with denosumab, and contrasts the pharmacokinetics of denosumab and the bisphosphonates. The importance of avoiding interventional dental treatment until denosumab has been withdrawn for six months cannot be overstated. PMID- 25131836 TI - Comparison of iSED and Ves-Matic Cube 200 Erythrocyte Sedimentation Rate Measurements With Westergren Method. AB - BACKGROUND: The erythrocyte sedimentation rate (ESR) test is performed widely in laboratories. Besides the traditional Westergren method, new methods have been developed for ESR measurements. We aimed to compare the instruments using new methods, iSED (Alcor Scientific) and Ves-Matic Cube 200 (Diesse Diagnostica Senese, Italy) with the Westergren method. METHODS: Blood samples from 136 patients were taken into EDTA tubes for automated analyzers and citrated tubes for Westergren method. Patients were divided into three groups- low, medium, and high-according to their sedimentation rates. Precision, stability, and interference studies of the methods were performed. RESULTS: The iSED sedimentation method (n = 136) yielded a slope of (0.61-0.84), with an intercept of (-2.32 to 1.89), which resulted in a mean bias of 13; and the Ves-Matic Cube 200 method (n = 136) yielded a slope of (0.85-1.00), with an intercept of (0.00 3.07), which resulted in a mean bias of 1.4 in Passing-Bablok regression analysis compared to the reference method. CONCLUSION: iSED sedimentation showed a poor correlation and a high bias (>10%) with the Westergren method, and Ves-Matic Cube 200 method showed a higher correlation and a lower bias than the iSED device when compared with Westergren reference method. These instruments should be carefully monitored. PMID- 25131837 TI - Magnetic-structure-stabilized polarization in an above-room-temperature ferrimagnet. AB - Above-room-temperature polar magnets are of interest due to their practical applications in spintronics. Here we present a strategy to design high temperature polar magnetic oxides in the corundum-derived A2BB'O6 family, exemplified by the non-centrosymmetric (R3) Ni3TeO6-type Mn(2+)2Fe(3+)Mo(5+)O6, which shows strong ferrimagnetic ordering with TC = 337 K and demonstrates structural polarization without any ions with (n-1)d(10)ns(0), d(0), or stereoactive lone-pair electrons. Density functional theory calculations confirm the experimental results and suggest that the energy of the magnetically ordered structure, based on the Ni3TeO6 prototype, is significantly lower than that of any related structure, and accounts for the spontaneous polarization (68 MUC cm( 2)) and non-centrosymmetry confirmed directly by second harmonic generation. These results motivate new directions in the search for practical magnetoelectric/multiferroic materials. PMID- 25131838 TI - Using the virtual brain to reveal the role of oscillations and plasticity in shaping brain's dynamical landscape. AB - Spontaneous brain activity, that is, activity in the absence of controlled stimulus input or an explicit active task, is topologically organized in multiple functional networks (FNs) maintaining a high degree of coherence. These "resting state networks" are constrained by the underlying anatomical connectivity between brain areas. They are also influenced by the history of task-related activation. The precise rules that link plastic changes and ongoing dynamics of resting-state functional connectivity (rs-FC) remain unclear. Using the framework of the open source neuroinformatics platform "The Virtual Brain," we identify potential computational mechanisms that alter the dynamical landscape, leading to reconfigurations of FNs. Using a spiking neuron model, we first demonstrate that network activity in the absence of plasticity is characterized by irregular oscillations between low-amplitude asynchronous states and high-amplitude synchronous states. We then demonstrate the capability of spike-timing-dependent plasticity (STDP) combined with intrinsic alpha (8-12 Hz) oscillations to efficiently influence learning. Further, we show how alpha-state-dependent STDP alters the local area dynamics from an irregular to a highly periodic alpha-like state. This is an important finding, as the cortical input from the thalamus is at the rate of alpha. We demonstrate how resulting rhythmic cortical output in this frequency range acts as a neuronal tuner and, hence, leads to synchronization or de-synchronization between brain areas. Finally, we demonstrate that locally restricted structural connectivity changes influence local as well as global dynamics and lead to altered rs-FC. PMID- 25131833 TI - Predictive models of glucose control: roles for glucose-sensing neurones. AB - The brain can be viewed as a sophisticated control module for stabilizing blood glucose. A review of classical behavioural evidence indicates that central circuits add predictive (feedforward/anticipatory) control to the reactive (feedback/compensatory) control by peripheral organs. The brain/cephalic control is constructed and engaged, via associative learning, by sensory cues predicting energy intake or expenditure (e.g. sight, smell, taste, sound). This allows rapidly measurable sensory information (rather than slowly generated internal feedback signals, e.g. digested nutrients) to control food selection, glucose supply for fight-or-flight responses or preparedness for digestion/absorption. Predictive control is therefore useful for preventing large glucose fluctuations. We review emerging roles in predictive control of two classes of widely projecting hypothalamic neurones, orexin/hypocretin (ORX) and melanin concentrating hormone (MCH) cells. Evidence is cited that ORX neurones (i) are activated by sensory cues (e.g. taste, sound), (ii) drive hepatic production, and muscle uptake, of glucose, via sympathetic nerves, (iii) stimulate wakefulness and exploration via global brain projections and (iv) are glucose-inhibited. MCH neurones are (i) glucose-excited, (ii) innervate learning and reward centres to promote synaptic plasticity, learning and memory and (iii) are critical for learning associations useful for predictive control (e.g. using taste to predict nutrient value of food). This evidence is unified into a model for predictive glucose control. During associative learning, inputs from some glucose-excited neurones may promote connections between the 'fast' senses and reward circuits, constructing neural shortcuts for efficient action selection. In turn, glucose inhibited neurones may engage locomotion/exploration and coordinate the required fuel supply. Feedback inhibition of the latter neurones by glucose would ensure that glucose fluxes they stimulate (from liver, into muscle) are balanced. Estimating nutrient challenges from indirect sensory cues may become more difficult when the cues become complex and variable (e.g. like human foods today). Consequent errors of predictive glucose control may contribute to obesity and diabetes. PMID- 25131830 TI - Histone deacetylases and their inhibitors in cancer, neurological diseases and immune disorders. AB - Epigenetic aberrations, which are recognized as key drivers of several human diseases, are often caused by genetic defects that result in functional deregulation of epigenetic proteins, their altered expression and/or their atypical recruitment to certain gene promoters. Importantly, epigenetic changes are reversible, and epigenetic enzymes and regulatory proteins can be targeted using small molecules. This Review discusses the role of altered expression and/or function of one class of epigenetic regulators--histone deacetylases (HDACs)--and their role in cancer, neurological diseases and immune disorders. We highlight the development of small-molecule HDAC inhibitors and their use in the laboratory, in preclinical models and in the clinic. PMID- 25131840 TI - Nomenclature for factors of the HLA system, April update 2014. PMID- 25131839 TI - Lipid-lowering effects of curcumin in patients with metabolic syndrome: a randomized, double-blind, placebo-controlled trial. AB - Human studies of curcumin extract on lipid-lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty-five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high-density lipoprotein cholesterol (HDL-C) significantly increased from 40.96 +/- 8.59 to 43.76 +/- 2.79 mg/dL (p < 0.05), and the level of low-density lipoprotein cholesterol (LDL) was significantly reduced (120.55 +/- 36.81 to 106.51 +/- 25.02 mg/dL, p < 0.05). The triglyceride-lowering effect, a reduction of 65 mg/dL, was also found in this study. In subgroups analysis, the consumption of curcumin may have a lowering cholesterol effect in male patients and an increasing HDL-C effect in female patients, both of which result in a decrease of T-Chol/HDL-C ratio. The intake of the curcumin extract of 1890 mg/day for 12 weeks was associated with lipid-lowering effect but did not improve weight and glucose homeostasis in the patients with metabolic syndrome. Daily curcumin consumption may be an alternative choice to modify cholesterol-related parameters, especially in metabolic syndrome patients. PMID- 25131841 TI - Modeling radiocesium transport from a river catchment based on a physically-based distributed hydrological and sediment erosion model. AB - The accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) in March 2011 resulted in the deposition of large quantities of radionuclides, such as (134)Cs and (137)Cs, over parts of eastern Japan. Since then high levels of radioactive contamination have been detected in large areas, including forests, agricultural land, and residential areas. Due to the strong adsorption capability of radiocesium to soil particles, radiocesium migrates with eroded sediments, follows the surface flow paths, and is delivered to more populated downstream regions and eventually to the Pacific Ocean. It is therefore important to understand the transport of contaminated sediments in the hydrological system and to predict changes in the spatial distribution of radiocesium concentrations by taking the land-surface processes related to sediment migration into consideration. In this study, we developed a distributed model to simulate the transport of water and contaminated sediment in a watershed hydrological system, and applied this model to a partially forested mountain catchment located in an area highly contaminated by the radioactive fallout. Observed discharge, sediment concentration, and cesium concentration measured from June 2011 until December 2012 were used for calibration of model parameters. The simulated discharge and sediment concentration both agreed well with observed values, while the cesium concentration was underestimated in the initial period following the accident. This result suggests that the leaching of radiocesium from the forest canopy, which was not considered in the model, played a significant role in its transport from the catchment. Based on the simulation results, we quantified the long-term fate of radiocesium over the study area and estimated that the effective half life of (137)Cs deposited in the study area will be approximately 22 y due to the export of contaminated sediment by land-surface processes, and the amount of (137)Cs remaining in the catchment will be reduced to 39% of the initial total within 30 y after contamination. This study provides a perspective on the transport of suspended sediments and radiocesium in catchments with similar land use and radiocesium contamination. PMID- 25131843 TI - Effect of passive polarizing three-dimensional displays on surgical performance for experienced laparoscopic surgeons. AB - BACKGROUND: Although the potential benefits of stereoscopic laparoscopy have been recognized for years, the technology has not been adopted because of poor operator tolerance. Passive polarizing projection systems, which have revolutionized three-dimensional (3D) cinema, are now being trialled in surgery. This study was designed to see whether this technology resulted in significant performance benefits for skilled laparoscopists. METHODS: Four validated laparoscopic skills tasks, each with ten repetitions, were performed by 20 experienced laparoscopic surgeons, in both two-dimensional (2D) and 3D conditions. The primary outcome measure was the performance error rate; secondary outcome measures were time for task completion, 3D motion tracking (path length, motion smoothness and grasping frequency) and workload dimension ratings of the National Aeronautics and Space Administration (NASA) Task Load Index. RESULTS: Surgeons demonstrated a 62 per cent reduction in the median number of errors and a 35 per cent reduction in median performance time when using the passive polarizing 3D display compared with the 2D display. There was a significant 15 per cent reduction in median instrument path length, an enhancement of median motion smoothness, and a 15 per cent decrease in grasper frequency with the 3D display. Participants reported significant reductions in subjective workload dimension ratings of the NASA Task Load Index following use of the 3D displays. CONCLUSION: Passive polarizing 3D displays improved both the performance of experienced surgeons in a simulated setting and surgeon perception of the operative field. Although it has been argued that the experience of skilled laparoscopic surgeons compensates fully for the loss of stereopsis, this study indicates that this is not the case. Surgical relevance The potential benefits of stereoscopic laparoscopy have been known for years, but the technology has not been adopted because of poor operator tolerance. The first laparoscopic operation was carried out using a prototype passive polarizing laparoscopic system in 2010. This is new three-dimensional (3D) technology offers a real option for 3D laparoscopic surgery where previous systems have failed. This study is the first to have been carried out using this technology. It is essential that new technologies are adopted only when there is robust evidence to support their use. Currently, there are concerns about the use of robotic technologies and whether advantages exist for patient care. If there are advantages, 3D must be playing a significant role. If so, perhaps the technology under investigation here offers potential to a greater spectrum of surgeons, as well as being a more affordable option. PMID- 25131842 TI - Anatomical landmarks for the localization of the greater palatine foramen--a study of 1200 head CTs, 150 dry skulls, systematic review of literature and meta analysis. AB - Accurate knowledge of greater palatine foramen (GPF) anatomy is necessary when performing a variety of anaesthesiological, dental or surgical procedures. The first aim of this study was to localize the GPF in relation to multiple anatomical landmarks. The second aim was to perform a systematic review of literature, and to conduct a meta-analysis on the subject of GPF position to aid clinicians in their practice. One-hundred and fifty dry, adult, human skulls and 1200 archived head computed tomography scans were assessed and measured in terms of GPF relation to other anatomical reference points. A systematic literature search was performed using the PubMed, Embase and Web of Science databases, and a meta-analysis on the subject of GPF relation to the maxillary molars was conducted. On average, in the Polish population, the GPF was positioned 15.9 +/- 1.5 mm from the midline maxillary suture (MMS), 3.0 +/- 1.2 mm from the alveolar ridge (AR) and 17.0 +/- 1.5 mm from the posterior nasal spine (PNS); 74.7% of GPF were positioned opposite the third maxillary molar (M3). Twenty-seven studies were included in the systematic review and 23 in the meta-analysis (n = 6927 GPF). The pooled prevalence of the GPF being positioned opposite the M3 was 63.9% (95% confidence interval = 56.6-70.9%). Concluding, the GPF is most often located opposite the M3 in the majority of the world's populations. The maxillary molars are the best landmarks for locating the GPF. In edentulous patients the most useful points for approximating the position of the GPF are the AR, MMS and PNS. This study introduces an easy and repeatable classification to reference the GPF to the maxillary molars. PMID- 25131844 TI - Some problems with determining the reliability of the EQ-5D-3L: commentary to "Value of EQ-5D in Mexican city older population with and without dementia (SADEM study)". PMID- 25131845 TI - Lysophosphatidic acid stimulates cell migration of satellite cells. A role for the sphingosine kinase/sphingosine 1-phosphate axis. AB - Regulation of the motility of skeletal muscle precursor cells, such as satellite cells, is critically important for their proper recruitment at the site of tissue damage, and ultimately for its correct repair. Here we show that lysophosphatidic acid (LPA), which is well-recognized as a powerful bioactive agent, strongly stimulates cell migration of activated murine satellite cells. The biological effect exerted by LPA was found to be induced via activation of LPA1 and LPA3 , being abolished by cell treatment with the antagonist Ki16425, and severely impaired by siRNA-mediated down-regulation of the two receptor isoforms. In contrast, silencing of LPA2 potentiated the stimulation of cell motility by LPA, suggesting that it is negatively coupled to cell migration. Pharmacological inhibition of both sphingosine kinase (SK) isoforms using VPC96047, or the selective blocking of SK1 using VPC96091, abolished cell responsiveness to LPA; in agreement, gene silencing of SK1 or SK2 significantly reduced the biological effect of LPA. Moreover, the LPA-dependent stimulation of cell chemotaxis was found to be impaired by down-regulation of the sphingosine 1-phosphate (S1P) receptors S1P1 or S1P4 by specific siRNAs. In summary, the results obtained support the notion that the sphingosine kinase/sphingosine 1-phosphate (SK/S1P) axis is critically involved in the mechanism by which LPA elicits its pro migratory action. This study provides compelling new information on the regulatory mechanisms of satellite cell motility, and reinforces the view that the SK/S1P signaling pathway plays a crucial role in the control of skeletal muscle precursor cell biology. PMID- 25131846 TI - The prevalence of keratoconus in a young population in Mashhad, Iran. AB - PURPOSE: To determine the prevalence of keratoconus and some associated factors in the students of Mashhad University of Medical Sciences, Iran. METHOD: In this cross sectional study, multistage cluster sampling was used to select the participants. All participants underwent retinoscopy, slit lamp examination, topography with the TMS-4 and corneal assessment with the Orbscan II. The diagnosis of keratoconus was based on both clinical evidence and the results of corneal imaging. RESULTS: Of 1280 selected students, 1073 agreed to participate in the study, and of those who agreed, 1027 fulfilled the inclusion criteria. 42.5% of the study population was male with a mean age of 26.1 +/- 2.3 years. The prevalence of keratoconus was 2.5% (n = 26) (95% confidence interval, CI 1.6 3.5). Eighteen students (69%) had bilateral keratoconus. Imaging of the cornea revealed that 70% of the keratoconics had nipple cones and the remaining had asymmetric bow-tie patterns. The prevalence of keratoconus was not significantly associated with age or gender (p > 0.05). In a multiple logistic regression model, family history (OR = 11.4, 95% CI: 2.5-51.3) and eye rubbing (OR = 6.3, 95% CI: 1.6-24.3) were significantly correlated with keratoconus. CONCLUSIONS: These results taken together with recent studies in the area suggest that keratoconus may have a higher prevalence in the Middle East and Asia than in Western Countries. PMID- 25131847 TI - Genetic testing and corresponding services among individuals with autism spectrum disorder (ASD). AB - The purpose of this study was to assess use of genetic testing and corresponding genetic services for children with Autism Spectrum Disorder (ASD). Survey data from 397 parents of individuals with ASD was collected using the Center for Autism and Related Disabilities client registry. Participants reported that 41.2% of the individuals with ASD had undergone any type of genetic testing. However, only 21.3% of individuals with ASD had been referred to a genetics specialist. Diagnosis and level of functioning were significantly associated with both referral to a genetics specialist and having undergone any genetic testing. In addition, Hispanic ancestry was associated with increased referral to genetic testing. Concerns about the limited benefits of genetic testing and prohibitive costs were potential barriers to pursuing genetic testing. Overall, low numbers of individuals with ASD have a history of undergoing genetic testing or receiving genetic services. Possible reasons include low referral rates as well as concerns by parents about cost and relevance, and lack of availability. These findings confirm the historical trend for providing genetic testing and genetic services to those with the greatest impairments. PMID- 25131848 TI - Evidence accumulates on the association between topiramate use early in pregnancy and the risk of oral clefts. PMID- 25131851 TI - Dynamic changes in metabolic profiles of rats subchronically exposed to mequindox. AB - Mequindox is widely used as an antibacterial veterinary drug and a feeding additive for farm animals in China. Although its toxicity has been widely studied, little is known regarding the metabolic effects of subchronic exposure to mequindox, which is vital for the health of meat producing livestock. Here, we characterized the dose- and time-dependent metabolic alterations in female Wistar rats subchronically exposed to mequindox through dietary supplementation at the level of 40, 110 and 280 mg kg(-1) for 13 weeks, employing a NMR based metabonomics approach with supplementary information from serum clinical chemistry. We found that urinary metabolic profiles were significantly affected in all dosed groups during the supplementation period; plasma and hepatic metabolic profiles were significantly affected only in rats dosed with moderate and high levels of mequindox. We also observed a return to control levels, for the profiles of urine and liver, at all dose levels after a two weeks washout period. However, this was not the case for the metabolic profiles of plasma from rats dosed at high levels. At the molecular level, we showed that subchronic exposure to mequindox resulted in tricarboxylic acid cycle (TCA cycle) stimulation, suppression of glycolysis, and promotion of gluconeogenesis and lipid oxidation in rats. In addition, subchronic exposure to mequindox induced oxidative stress in rats. Furthermore, a disturbance of gut microbiota, manifested by alterations in the urinary excretion of hippurate, phenylacetylglycine, 3-(3-hydroxyphenyl)propionate, p-cresol glucuronide, methylamine, dimethylamine, and formate, was associated with mequindox exposure. The present study provided important holistic metabolic information on the effects of subchronic dosage of mequindox on rats, which is useful for evaluating the safety of mequindox usage in meat producing animals. PMID- 25131852 TI - Role of hematopoietic stem cell transplantation in multiple myeloma. AB - High-dose therapy followed by autologous stem cell transplantation (ASCT) has been the standard frontline consolidative therapy for patients with newly diagnosed multiple myeloma (MM) for > 2 decades. This approach has resulted in higher complete response (CR) rates and increased event-free survival and overall survival (OS) compared with conventional chemotherapy. The emergence of novel agent-based therapy combined with ASCT has revolutionized MM therapy by improving the CR rates and OS, raising questions concerning the role of hematopoietic stem cell transplantation in this setting. PMID- 25131850 TI - In utero and early childhood exposure to arsenic decreases lung function in children. AB - The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 ug l-1. The mean urinary As level registered in the studied subjects was 141.2 ug l 1 and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. PMID- 25131853 TI - Isolated mesenteric CD20-positive myeloid sarcoma. PMID- 25131854 TI - Clinicopathologic analysis of POEMS syndrome and related diseases. AB - BACKGROUND: POEMS syndrome, a rare paraneoplastic disease, is related to multiple organs, multiple systems, and multiple disciplines and can be mistaken for other disorders. Consequently, the diagnoses are often delayed. In this work we studied the clinicopathologic characteristics of the POEMS syndrome to improve early diagnosis to prevent irreversible damage. PATIENTS AND METHODS: We conducted a clinicopathologic analysis of 9 cases of POEMS and made a differential diagnosis with related diseases. RESULTS: The patients with POEMS syndrome were shown to have complicated clinical characteristics, including peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes, extravascular volume overload, sclerotic bone lesions, thrombocytosis, and Castleman disease. POEMS syndrome shared many elements with other diseases and the key way to differentiate them was to determine whether there were other fundamental POEMS syndrome symptoms or signs. The level of M-protein in serum and plasma cells in bone marrow of POEMS patients was lower than that of patients with multiple myeloma (MM). Sclerotic bone lesions were a distinctive feature in patients with POEMS, compared with in those with MM. CONCLUSION: Some unique clinicopathologic characteristics of POEMS syndrome can be used for differential diagnosis. This study provides increased awareness of POEMS syndrome. PMID- 25131855 TI - Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation. AB - Varicella zoster virus (VZV), a threat for hematopoietic stem cell transplantation (HSCT) recipients, is still one of the most common viral pathogens that affect these patients with a reported incidence ranging between 17% and 50% in the post transplantation period. Valganciclovir (V-GCV), a valine ester pro-drug of GCV orally administrable, has recently shown great activity against CMV infections, but there are no reports of its clinical efficacy against VZV. We here report a case history of a patient with positive serologic test for VZV, who underwent allogeneic HSCT and developed an atypical varicella-like illness. First-line therapy with foscarnet had to be discontinued due rapid development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and therefore was switched to V-GCV. The renal impairment and skin lesions of the patient fully recovered after few days of therapy, even though the patient had complete lymphocyte depletion. This is the first case of a patient with chickenpox-like illness treated successfully with V-GCV. PMID- 25131856 TI - Hepatitis C virus infection in China: an emerging public health issue. AB - Hepatitis C virus now represents a global viral pandemic and is the fourth most commonly reported infectious disease in China. Information on China's national HCV epidemic was limited to cross -sectional seroprevalence studies of special populations, and a national surveillance effort had been launched to inform prevention and control. We analysed novel data from two national databases: (i) China's national medical HCV case report system and (ii) the national disease sentinel surveillance system. Between 1997 and 2012, reporting incidence of medical cases for HCV infection rose from 0.7 to 15.0 cases per 100 000 with the largest burden of disease concentrated among individuals over 35 years of age, rural residents and those tested as part of routine screening. Between 2010 and 2012, disease sentinel surveillance identified the highest HCV seropositive rates among persons who use drugs and haemodialysis patients, with far lower but not negligible rates among sexually active population. The concentration of cases among older age groups is consistent with past studies of age-specific prevalence rates in Asia. Differences across regions and testing modes suggest diverse biological and social forces driving the spread of HCV in China. Surveillance data show ongoing transmission, particularly among persons who use drugs and persons undergoing invasive medical treatments, particularly haemodialysis. Improvements in case detection and data reporting systems will be critical for understanding current drivers of transmission and identifying key areas for prevention. PMID- 25131857 TI - Informal social networks of people with profound intellectual and multiple disabilities: relationship with age, communicative abilities and current living arrangements. AB - BACKGROUND: People with profound intellectual and multiple disabilities (PIMD) have limited informal social contacts. Research to determine the factors which can positively influence establishing sound informal social contacts is required. MATERIALS AND METHODS: Regression analysis for 200 people with PIMD was used to analyse how age, communicative abilities and current living arrangements were related to the number and frequency of their contacts. RESULTS: Only age was negatively related to both the number and frequency of social contacts. Current living arrangements related only to the frequency of contacts. Communicative abilities related to neither. CONCLUSIONS: Like people with intellectual disabilities, age and living arrangements are related to the informal social networks of people with PIMD. However, for people with PIMD, these networks are already more limited. Therefore, professionals need to be attentive to the maintenance and/or expansion of the social networks of people with PIMD at an early stage. PMID- 25131859 TI - Expression, purification, and micelle reconstitution of antimicrobial piscidin 1 and piscidin 3 for NMR studies. AB - Piscidin 1 and piscidin 3, which were discovered in the mast cells of hybrid striped sea bass, are homologous antimicrobial peptides that are active against drug-resistant bacteria. Piscidin 1, the more antimicrobial and hemolytic peptide, also has anti-HIV-1 and anti-cancer properties. To understand the reasons underlying the different biological activities of the two peptides and identify principles to design antimicrobial drugs with improved efficacy and lower toxicity, their atomic-level structures must be obtained under physiologically-relevant conditions. High-resolution backbone structures of both piscidins exist in the presence of hydrated phospholipid bilayers but full structures that include the side chains are missing. Here, the piscidins 1 and 3 genes were cloned into the TrpLE vector. The corresponding TrpLE-piscidin fusion partners were expressed in Escherichiacoli and recovered from inclusion bodies. Following steps that included Ni-NTA chromatography, cyanogen bromide cleavage of the fusion proteins, and reverse-phase HPLC, purified piscidins 1 and 3 were recovered in very good yield and characterized by NMR. High quality (15)N-(1)H HSQC spectra of piscidins 1 and 3 bound to SDS micelles were collected, demonstrating the feasibility of producing and purifying the isotopically-labeled piscidin peptides required to determine their full structures by multidimensional NMR spectroscopy. PMID- 25131858 TI - Expression of recombinant human mast cell chymase with Asn-linked glycans in glycoengineered Pichia pastoris. AB - Recombinant human mast cell chymase (rhChymase) was expressed in secreted form as an active enzyme in the SuperMan5 strain of GlycoSwitch(r) Pichia pastoris, which is engineered to produce proteins with (Man)5(GlcNAc)2 Asn-linked glycans. Cation exchange and heparin affinity chromatography yielded 5mg of active rhChymase per liter of fermentation medium. Purified rhChymase migrated on SDS-PAGE as a single band of 30 kDa and treatment with peptide N-glycosidase F decreased this to 25 kDa, consistent with the established properties of native human chymase (hChymase). Polyclonal antibodies against hChymase detected rhChymase by Western blot. Active site titration with Eglin C, a potent chymase inhibitor, quantified the concentration of purified active enzyme. Kinetic analyses with succinyl-Ala Ala-Pro-Phe (suc-AAPF) p-nitroanilide and thiobenzyl ester synthetic substrates showed that heparin significantly reduced KM, whereas heparin effects on kcat were minor. Pure rhChymase with Asn-linked glycans closely resembles hChymase. This bioengineering approach avoided hyperglycosylation and provides a source of active rhChymase for other studies as well as a foundation for production of recombinant enzyme with human glycosylation patterns. PMID- 25131860 TI - Expression and biochemical characterization of recombinant human epididymis protein 4. AB - Whey acidic proteins (WAP) belong to a large gene family of antibacterial peptides that perform critical immune system functions. The function of human epididymis protein 4 (HE4), a 124-amino acid long polypeptide that has two whey acidic protein four-disulfide core (WFDC) domains, is not well studied. Here, a fusion gene encoding the HE4 protein fused to an IgG1 Fc domain was constructed. The recombinant HE4 protein was expressed as a secretory protein in Pichia pastoris and mammalian HEK293-F cells and was subsequently purified. Our data suggested that the HE4 protein produced by these two expression systems bound to both gram-negative and gram-positive bacteria, but demonstrated slightly inhibitory activity towards the growth of Staphylococcus aureus. Moreover, HE4 exhibited proteinase inhibitory activity towards trypsin, elastase, matrix metallopeptidase 9, and the secretory proteinases from Bacillus subtilis. The effects of glycosylation on the biochemical characterization of HE4 were also investigated. LC-ESI-MS glycosylation analysis showed that the high-mannose glycosylated form of HE4 expressed by P. pastoris has lower biological activity when compared to its complex-glycosylated form produced from HEK293-F cells. The implications of this are discussed, which may be provide theoretical basis for its important role in the development of cancer and innate immune system. PMID- 25131861 TI - Depression, anxiety and self-care behaviours of young adults with Type 2 diabetes: results from the International Diabetes Management and Impact for Long term Empowerment and Success (MILES) Study. AB - AIM: Young adults with Type 2 diabetes have higher physical morbidity and mortality than other diabetes sub-groups, but differences in psychosocial outcomes have not yet been investigated. We sought to compare depression and anxiety symptoms and self-care behaviours of young adults with Type 2 diabetes with two matched control groups. METHODS: Using cross-sectional survey data from the Australian and Dutch Diabetes Management and Impact for Long-term Empowerment and Success (MILES) studies, we matched 93 young adults (aged 18-39 years) with Type 2 diabetes (case group) with: (i) 93 older adults ( >= 40 years) with Type 2 diabetes (Type 2 diabetes control group; matched on country, gender, education, diabetes duration and insulin use) and (ii) 93 young adults with Type 1 diabetes (Type 1 diabetes control group; matched on country, gender, age and education). Groups were compared with regard to depression symptoms (nine-item Patient Health Questionnaire), anxiety symptoms (seven-item Generalised Anxiety Disorder questionnaire) and frequency of selected self-care behaviours (single item per behaviour). RESULTS: Participants in the case group had higher depression scores (Cohen's d = 0.40) and were more likely to have clinically meaningful depressive symptoms (Cramer's V = 0.23) than those in the Type 2 diabetes control group. Participants in the case group had statistically equivalent depression scores to the Type 1 diabetes control group. The groups did not differ in anxiety scores. Those in the case group were less likely than both control groups to take insulin as recommended (Cramer's V = 0.24-0.34), but there were no significant differences between the groups in oral medication-taking. The case group were less likely than the Type 2 diabetes control group to eat healthily (Cramer's V = 0.16), and less likely than the Type 1 diabetes control group to be physically active (Cramer's V = 0.15). CONCLUSIONS: Our results suggest that Type 2 diabetes is as challenging as Type 1 diabetes for young adults and more so than for older adults. Young adults with Type 2 diabetes may require more intensive psychological and self-care support than their older counterparts. PMID- 25131862 TI - [Carcinoma unknown primary-clinical practice]. AB - Carcinomas of unknown primary are cancers that are pathologically diagnosed as carcinomas based on the findings of metastatic lesion biopsy but in which the primary site remains unknown even after thorough and detailed examinations.In the clinical setting, pathological diagnosis and diagnostic imaging are very important for cases of carcinoma of unknown primary. When examinations do not identify the primary tumor, carcinoma cases are treated as carcinoma of unknown primary.In clinical practice, it is very important not to miss cases of favorable prognosis group, which is 20% of unknown cancer. Recently, microarray studies have been performed for cases of carcinoma of unknown primary. PMID- 25131863 TI - [New era of the treatment of CRPC in Japan]. AB - In Y2014, several new agents targeted to castration resistant(recurrent)prostate cancer; CRPC, are approved in Japan. Although such good news comes 2-3 years behind Western, it may improve the outcomes of the CRPC patients in Japan. In this issue, enzalutamide, abiraterone, and cabazitaxel are discussed by each experts from the productive industries. In addition, the experts from urological field and medical oncology field describe the role of each discipline. PMID- 25131864 TI - [Enzalutamide-a novel androgen receptor inhibitor that provides treatment options for patients with castration-resistant prostate cancer]. AB - The recent emergence of new hormonal or chemotherapeutic drugs has resulted in a paradigm shift in the treatment of castration-resistant prostate cancer(CRPC). Enzalutamide is a rationally designed, orally administered androgen receptor(AR)inhibitor. It inhibits multiple points in the androgen receptor signalling pathway, which is considered an important driver of CRPC, including the inhibition of androgen binding to the AR, nuclear translocation of the AR complex, and binding of the AR complex to deoxyribonucleic acid(DNA). Unlike other anti-androgens(such as bicalutamide), enzalutamide does not act as a partial AR agonist. The first in human phase I/II trial was conducted in the United States in both chemotherapy-naive patients and postchemotherapy patients with progressive metastatic CRPC(mCRPC). The results showed encouraging antitumor activity of enzalutamide by considering all outcomes assessed in the trial. The first reported phase III trial was a randomized, double-blind, placebo controlled, multinational study involving 1,199 patients with mCRPC that progressed even after docetaxel therapy(AFFIRM trial). Enzalutamide was associated with significant benefits over the placebo considering time-to-event outcomes(i.e. prolonged overall survival[OS], delayed time to prostatic specific antigen[PSA]progression[TTPP], prolonged radiographic progression free survival[rPFS], time to the first skeletal related event[SRE])as well as objective response outcomes(i.e. PSA, soft tissue, and quality of life[QOL]). On the basis of the AFFIRM results, Astellas and Medivation filed a new drug application with the United States Food and Drug Administration and the European Medicines Agency in 2012, and obtained their approval. Another phaseI/II enzalutamide trial was conducted in both chemotherapy-naive patients and post chemotherapy pa- tients with progressive mCRPC. Enzalutamide at a dose of 160mg/day was well tolerated, and it showed pharmacokinetic characteristics, adverse events, and anti-tumor activity profiles similar to that of the non Japanese population. On the basis of the results of the studies summarized above, a new drug application was submitted to the Ministry of Health, Labour, and Welfare of Japan in May 2013 and obtained the approval in Mar 2014. The second phase III trial was a randomized, double-blind, placebo-controlled, multinational study of 1,717 chemotherapy- naive patients with CRPC(PREVAIL trial). An interim analysis recently demonstrated the significant benefits of enzalutamide over the placebo considering both OS and rPFS. In light of these results, the Independent Data Monitoring Committee (IDMC)advised terminating the study early, and suggested treating the patients in the placebo group with enzalutamide. This paper reviews the developmental history of enzalutamide, its pharmacokinetic and pharmacodynamic characteristics, as well as available efficacy and tolerability data yielded in clinical trials of patients with CRPC. PMID- 25131865 TI - [Abiraterone acetate(ZYTIGA(r))-development and literature review]. AB - Abiraterone acetate(AA)has been approved in more than 80 countries for the treatment of patients with metastatic castration-resistant prostate cancer(mCRPC). In July 2013, a marketing approval application for AA was submitted to the Japanese Ministry of Health, Labour, and Welfare. AA is a selective inhibitor of CYP17A1, a crucial enzyme for androgen biosynthesis. AA exerts its anti-tumor activity by directly inhibiting androgen production at all three sources, i. e., the testes, adrenal glands, and tumor itself. Data from international phase III studies and phase I and II studies in Japan have indicated that AA improves the overall survival and quality of life(QoL)of patients with mCRPC. Herein, we have summarized the development of AA and the results of important international and local clinical trials in Japan. In addition, the effect of food on AA bioavailability, concomitant steroid use, and liver function test abnormalities have been discussed regarding the appropriate use of AA. PMID- 25131866 TI - [Cabazitaxel--a next-generation taxane for the treatment of patients with metastatic castration-resistant prostate cancer]. AB - Prostate cancer is a heterogeneous disease that responds variably to available agents, particularly androgen receptor(AR)- targeting agents. In preclinical models, cabazitaxel, a second-generation taxane, demonstrated enhanced antitumor activity when compared with docetaxel. In subsequent clinical trials, cabazitaxel was associated with pharmacokinetic, safety, and tolerability profiles consistent with those of previous taxanes. In the pivotal phase III study(TROPIC; NCT00417079), cabazitaxel led to significantly improved overall survival in patients with metastatic castration-resistant prostate cancer(mCRPC), compared with mitoxantrone, when both were administered in combination with prednisone/prednisolone(median survival: 15.1 months[95%confidence interval(CI): 14.1-16.3]vs 12.7 months[95% CI: 11.6-13.7], hazard ratio(HR): 0.70[95% CI: 0.59 0.83], p<0.0001), and it also extended progression-free survival. Furthermore, a long-term analysis of the TROPIC trial revealed that the survival benefit with cabazitaxel was maintained at 2 years, with 60(15.9%)patients in the cabazitaxel group and 31(8.2%)patients in the mitoxantrone group surviving for B2 years(odds ratio: 2.11, 95% CI: 1.33-3.33). Cabazitaxel also provides pain palliation similar to that provided by using mitoxantrone. The safety profile of cabazitaxel is consistent with that of first-generation taxanes, and gastrointestinal(predominantly diarrhea)and hematologic(mainly neutropenia)adverse events are the most frequently reported. Clinical trial data suggest that these events can be managed with careful monitoring and dose reduction where necessary. In addition, treatment with granulocyte colony stimulating factor(G-CSF)can mitigate hematologic adverse events, whereas supportive treatment with antiemetic and antidiarrheal agents may ameliorate gastrointestinal symptoms. The treatment paradigm for mCRPC is evolving rapidly with the emergence of data for new agents, leading to maximization of patient benefits. The proven efficacy and tolerability profiles of cabazitaxel suggest the promising role of this agent within this paradigm. PMID- 25131867 TI - [Role of urologists in the era of new treatment modalities for CRPC in Japan]. AB - New medical treatment modalities for castration resistant prostate cancer(CRPC), including hormonal therapy and chemotherapy, will be approved in Japan. Here, we discuss the management of these new treatment strategies by urologists. PMID- 25131868 TI - [Roles of medical oncologists in the new era of CRPC therapy in Japan]. AB - Currently, the standard therapy for advanced prostate cancer is endocrine therapy(luteinizing hormone-releasing hormone [LH-RH]agonists alone or LH RHagonists plus antiandrogens). However, most patients eventually become resistant to these therapies as well as castration therapy. New endocrine therapies for castration-resistant prostate cancer(CRPC)have been developed. Abiraterone, a CYP17 inhibitor, and enzalutamide, a novel androgen receptor antagonist, have been shown to improve the overall survival, and they are set to be approved in Japan soon. Moreover, docetaxel and cabazitaxel have been established as first- and second-line chemotherapeutic drugs, respectively. Although there is currently no established molecular target drug for CRPC, some drugs such as cabozantinib seem to be effective, and they may be used in the future. In these situations of new drug development, the contribution of medical oncologists is predictable. While medical oncologists cannot play central roles in all aspects of drug therapy for urological malignancies in Japan, they must play roles in certain aspects such as new drug development starting from phase I trials, improving multidisciplinary care for adverse events, and promoting translational research. PMID- 25131869 TI - [Factors affecting adherence of breast cancer patients to adjuvant hormonal therapy and validation of the evaluation method]. AB - BACKGROUND: The long-term use of hormonal therapy is important for the treatment of patients with breast cancer. Therefore, we evaluated the methods used for measuring adherence and examined factors that influence compliance. Our goal was to improve overall adherence to the treatment. METHODS: Retrospective analyses by using electronic medical records and questionnaires were performed on 294 patients with breast cancer. The patients were classified into 2 groups based on the mean number of days when a dose was missed over a period of 28 days: group A(range, 0-3 days, n=272)and group B (range, B4 days, n=22). Factors that may influence adherence, including age, duration of hormonal therapy, the drug administered in hormonal therapy, the surgical method, axillary lymph node dissection, and adjuvant chemotherapy, were compared between both groups. RESULTS: The adherence rates calculated from electronic medical records and questionnaires were similar. The proportion of patients younger than 50 years was 30% in group A and 50% in group B(p<0.05). Additionally, there was a difference in the duration of hormone therapy(752 days vs 981 days in groups A and B, respectively; p< 0.05). Additional factors that are related to low-risk cancer related procedures, such as breast conserving surgery, may also be linked to poor adherence. CONCLUSION: Young age and long duration of hormonal therapy are possibly related to poor adherence. Therefore, pharmacists should identify and manage these patients to increase adherence. PMID- 25131870 TI - [Efficacy and toxicity of pemetrexed monotherapy for previously untreated elderly patients with non-squamous cell lung cancer with wild-type(or unknown)EGFR status]. AB - BACKGROUND: The efficacy of docetaxel, vinorelbine, or gemcitabine monotherapy in previously untreated elderly patients with non-small cell lung cancer has been reported.Pemetrexed monotherapy has shown clinically equivalent efficacy to docetaxel, a standard therapeutic option, in patients with previously treated non small cell lung cancer and in those with a lower incidence of toxicity such as febrile neutropenia. OBJECTIVE: In the present study, we aimed to investigate the efficacy and toxicity of pemetrexed in previously untreated elderly patients with non-squamous cell lung cancer and compare the results with those of docetaxel, considered a standard chemotherapeutic agent. METHODS: We retrospectively reviewed the medical records of patients with non-squamous cell lung cancer with wild-type(or unknown)epidermal growth factor receptor status who received pemetrexed or docetaxel monotherapy as first-line chemotherapy. RESULTS: We analyzed 6 patients with lung adenocarcinoma in the pemetrexed group and 6 patients with lung adenocarcinoma in the docetaxel group. The median progression free survival was 3.6 months for patients receiving pemetrexed and 3.1 months for those receiving docetaxel(p=0.45). The median overall survival was 14.8 months in the pemetrexed group and 10.9 months in the docetaxel group(p=0.36).Patients who received docetaxel were more likely to have grade 3 or 4 neutropenia and febrile neutropenia than those receiving pemetrexed.However, 2 patients who received pemetrexed showed grade 3 pneumonitis. CONCLUSION: Pemetrexed monotherapy is a promising treatment for previously untreated elderly patients with non-squamous cell lung cancer. PMID- 25131871 TI - [Value of the palliative prognostic index, controlling nutritional status, and prognostic nutritional index for objective evaluation during transition from chemotherapy to palliative care in cases of advanced or recurrent gastrointestinal cancer]. AB - OBJECTIVE: We investigated whether objective evaluation by using the palliative prognostic index(PPI), controlling nutritional status(COUNT), and prognostic nutritional index(PNI)can provide prognostic information during the transition from chemotherapy to palliative care in patients with advanced or recurrent gastrointestinal cancer. METHODS: The subjects were 28 patients with gastrointestinal cancer who died of their disease between January 2009 and June 2012. We compared the PPI, COUNT, and PNI scores between patients who died within 90 days of completing chemotherapy(Group A, n=14)and patients who survived for 90 or more days(Group B, n=14). RESULTS: The PPI score for Group A(4.0)was significantly higher than that for Group B(0.8)(p<0.001). The COUNT score was also significantly higher for Group A(6.3)than for Group B (3.9)(p=0.033). A significant difference in survival was evident when the cutoff value for PNI was set at 40 in the critical region(68/118, p=0.04). CONCLUSION: Our study suggests that the PPI, COUNT, and PNI may be useful for objective evaluation during the transition from chemotherapy to palliative care. PMID- 25131872 TI - [The efficacy and safety of FOLFIRI or combined FOLFIRI and bevacizumab treatment as second-line chemotherapy for metastatic colorectal cancer patients aged 75 years and older]. AB - The safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic colorectal cancer patients >= 75 years was retrospectively evaluated. We analyzed 106 patients, who received FOLFIRI or a combination of FOLFIRI and bevacizumab following oxaliplatin-based first-line chemotherapy. The clinical characteristics and outcome in elderly patients >=75 years(elderly[EP]group; n=18)were compared with those in patients aged<75 years(control group; n=88). The number of patients treated by a combination of FOLFIRI and bevacizumab in the EP group was lower than that in the control group (27.8% vs 55.7%; p=0.03). The comparison revealed no significant differences in response rate, progression-free survival, overall survival, and the frequency of overall adverse events after the start of second line chemotherapy, although the frequency of anemia(Bgrade 3, p=0.07)and alopecia(grade 1/2, p=0.054)tended to be higher in the EP group than in the control group. Although this study retrospectively analyzed a limited number of patients, our results indicate that the safety and efficacy of FOLFIRI as second line chemotherapy for metastatic colorectal cancer are almost equal in patients >= 75 years and those aged<75 years. PMID- 25131873 TI - [Opioid induction using rapid release drugs and the shift to fentanyl patches]. AB - SUBJECT AND METHODS: From April 2011 to March 2013, 20 patients with cancer pain that was not controlled by non-opioid analgesics were treated with a short-acting opioid for cancer pain management.The primary carcinoma sites were the stomach( n=5), colo-rectum(n=5), lungs(n=3), urinary bladder(n=2), breast(n=2), pancreas(n=2), and liver(n=1). The analgesic effects and adverse events were evaluated, and a shift to fentanyl patches was made for patients whose cancer pain was relieved.After the shift, the efficiency and safety were validated. RESULTS: All 6 patients with a numeric rating scale (NRS)less than 5 at the time of opioid induction had a good analgesic effect, and in only 1 patient, grade 2 constipation and grade 3 anorexia was observed.Of the 14 patients who had an NRS of 6 or greater, 11 had a good analgesic effect.However, 3 patients experienced no effect, and their survival periods after opioid induction were very short.In the 11 patients with good pain control, only 3 patients exhibited grade 2 adverse events.Nine patients out of 17 with a good analgesic effect caused by short acting opioids were shifted to fentanyl patches, and 8 patients were under good analgesic control for 2 weeks or more. CONCLUSION: Opioid induction using rapid release drugs was effective and safe.However, these drugs should be clinically considered at an early stage.Furthermore, in patients where a shift to a fentanyl patch was possible, good long-term pain control was achieved. PMID- 25131874 TI - [A case of mediastinal growing teratoma syndrome with acute megakaryoblastic leukemia]. AB - We report a case of a 38-year-old man who was diagnosed with a mediastinal germ cell tumor. After induction chemotherapy, the tumor marker levels normalized, but the tumor itself continued to grow. Surgical resection was performed successfully, but the patient developed acute megakaryoblastic leukemia 6 months later, and induction and consolidation therapies failed to achieve remission. Leukemia cells invaded the central nervous system following hematopoietic stem cell transplantation, and the patient died 5 months after being diagnosed with leukemia. This very rare case of a mediastinal germ cell tumor met the criteria for "growing teratoma syndrome", against a background of acute megakaryoblastic leukemia. PMID- 25131875 TI - [Myelodysplastic syndrome with rapid disease progression after withdrawal of treatment with azacitidine]. AB - A 73-year-old woman was diagnosed with myelodysplastic syndrome(MDS). After 11 courses of treatment with azacitidine( AZA), her hemoglobin level and platelet count improved significantly, and she became transfusion independent. Therefore, treatment was discontinued and follow-ups were maintained. Three months later, her platelet count reduced again; we therefore treated her again with AZA. However, MDS transformed to acute myeloid leukemia in the 14th course, and she died 19 months after the initial diagnosis. AZA is an important drug for treating MDS, but premature withdrawal of treatment might cause rapid disease progression. In case treatment is discontinued, the patient needs to be carefully observed. PMID- 25131876 TI - [Two cases of thymic carcinoid treated with octreotide long-acting repeatable]. AB - Thymic carcinoid is a rare disease that accounts for 3.1% of thymic tumors and 1.8-6% of all carcinoid tumors in Japan. Advanced thymic carcinoid has a 5-year survival rate of 28-31%.Compared with carcinoid tumors that arise in other organs, thyroid carcinoid tumors carry a relatively worse prognosis, and the most effective therapeutic strategy is thought to be surgical resection.However, for patients with recurrence and distant metastases, multimodal therapy including radiotherapy and/or chemotherapy is usually applied.No chemotherapy treatment regimen has been established in Japan, although the National Comprehensive Cancer Network Guidelines proposed the application of octreotide long-acting repeatable(LAR).In this report, we present two cases of thymic carcinoid that were treated with octreotide LAR and achieved long-term survival. PMID- 25131877 TI - [A case of gastric adenosquamous carcinoma with peritoneal dissemination in which treatment with S-1 plus paclitaxel therapy resulted in improved long-term survival]. AB - Gastric adenosquamous carcinoma is a rare malignancy with a poor prognosis. We recently performed palliative gastrectomy for a gastric adenosquamous carcinoma with peritoneal dissemination and provided a course of systemic chemotherapy with S-1 plus paclitaxel(PTX)after the surgery. No serious adverse events were observed, and treatment with S-1 plus PTX was continued for 1 year before being switched to adjuvant chemotherapy with S-1 alone for another year. The tumor maker levels normalized within 2 months of the initial treatment, and the peritoneal dissemination could no longer be detected by abdominal computed tomography(CT). The patient remained in clinical remission and maintained long term survival of over 8 years. PMID- 25131878 TI - [A patient with paclitaxel hypersensitivity treated with nab-paclitaxel]. AB - A 63-year-old man with multiple liver metastases from gastric cancer was treated with S-1 plus cisplatin; however, the number of multiple liver metastases increased. The patient received paclitaxel(PTX)treatment, but a hypersensitivity reaction occurred after administering the second dose; therefore, he received docetaxel treatment. A hypersensitivity reaction occurred after administering the first dose of docetaxel; therefore, he received irinotecan treatment. However, irinotecan administration was stopped because of severe diarrhea and weight reduction. Subsequently, at the patient's request, nab-PTX treatment was initiated by administering a premedication regimen of dexamethasone(8mg)and chlorpheniramine(10mg); no hypersensitivity reactions were reported thereafter. Nab-PTX is a contraindication; however, it might be possible to use nab-PTX for treating patients with PTX hypersensitivity. PMID- 25131879 TI - [A case of complete response to multiple liver metastasis of gastric cancer after discontinuation of S-1 administration]. AB - An 80-year-old man was diagnosed with advanced gastric cancer and underwent distal gastrectomy. Although the pathological Stage of the cancer was III A, he refused adjuvant chemotherapy. One year later, CT revealed multiple liver metastases. Therefore, he was started with S-1 administration and a complete response was obtained at 10 months after starting S-1 administration. He has maintained a complete response for 22 months after S-1 discontinuation. PMID- 25131880 TI - [Successful treatment of advanced sigmoid colon cancer with liver metastases with cetuximab monotherapy as first-line treatment-a case report]. AB - The prognosis for patients diagnosed with advanced colorectal cancer with liver metastases is poor. Chemotherapy should be administered with caution in such patients because of complications due to severe liver dysfunction. We report here the successful management of a case of advanced sigmoid colon cancer, with icterus due to severe liver metastases, treated with cetuximab as first-line therapy. A 72-year-old man presented at our institution with complaints of severe general fatigue, tarry stools, and abdominal distention. He was diagnosed with advanced sigmoid colon cancer with multiple liver metastases. Clinical examination revealed the presence of ascites. The patient had an Eastern Cooperative Oncology Group(ECOG) performance status(PS)score of 3. A biopsy specimen of the primary tumor showed well-moderately differentiated adenocarcinoma without KRAS mutation. He was diagnosed with advanced sigmoid colon cancer with multiple hepatic metastases. Cetuximab monotherapy was initiated as first-line treatment. After 4 courses of cetuximab monotherapy, results of laboratory tests showed an improvement, and a computed tomography(CT)scan revealed a regression in the size of the liver metastases. Because the results of liver function tests and the ECOG PS scores improved, we initiated combination chemotherapy with 5-fluorouracil, Leucovorin, oxaliplatin(FOLFOX), and cetuximab. This regimen was well tolerated up to 14 courses, during which the only adverse reaction reported was a rash of grade 2 toxicity. Thereafter, disease progression in the form of liver metastases resulted in a change in the combination therapy to irinotecan and S-1(IRIS)as second-line chemotherapy. Thereafter, irinotecan and panitumumab were administered as third-line therapy. The patient continued chemotherapy on an outpatient basis; however, he died due to disease progression 18 months after his first visit. PMID- 25131881 TI - [A case of post-operative recurrence of pancreatic cancer in the residual pancreas treated by resection of the residual pancreas following radiological complete response achieved with second-line FOLFIRINOX]. AB - A 65-year-old woman with carcinoma of the pancreatic body underwent Whipple's operation. After surgery, adjuvant chemotherapy with gemcitabine alone, and S-1 combined with gemcitabine was conducted. But one year later, a recurrent tumor was detected in the pancreatic tail. We administered FOLFIRINOX treatment for the recurrent tumor. After 6 courses, FOLFIRINOX treatment resulted in a partial response, and after 9 courses, a radiological complete response was achieved. We could then perform total pancreatotectomy and resection of the metastatic liver tumor. FOLFIRINOX as a second-line treat- ment was effective and safe in this case. In cases of gemcitabine and/or S-1 failure, FOLFIRINOX treatment should be considered. PMID- 25131883 TI - [A case of esophageal squamous cell carcinoma with an adenocarcinoma component that dedifferentiated after chemotherapy]. AB - CASE: A 69-year-old man was diagnosed with advanced esophageal cancer(well differentiated squamous cell carcinoma). Neoadjuvant chemotherapy consisting of nedaplatin and 5-fluorouracil(5-FU)was initiated. After two courses of chemotherapy, the patient was judged to have achieved a clinical complete response. The patient then decided against undergoing surgery and opted instead to continue with the chemotherapy, receiving five courses in total. However, the esophageal cancer recurred, and subtotal esophagectomy was performed in January 2011. Squamous cell carcinoma with an adenocarcinoma component, which consisted of poorly differentiated squamous cell carcinoma and tubular adenocarcinoma cells, was observed at the primary site. Metastasis of the cancer to the liver was detected 2 months after surgery. The subsequent administration of four courses of docetaxel to the patient did not result in any beneficial effects, and the patient developed carcinomatous pleurisy and died of this complication in November 2011. The patient survived for a total of 21 months after starting chemotherapy. In this case, the chemotherapy itself may have resulted in the dedifferentiation of a well differentiated squamous cell carcinoma to result in a poorly differentiated squamous cell carcinoma with an adenocarcinoma component. PMID- 25131882 TI - [A case of bleeding stomal varices during the course of oxaliplatin-based chemotherapy for recurrent rectal cancer]. AB - A 51-year-old man with a history of an abdominoperineal resection of the rectum and colostomy for rectal cancer underwent chemotherapy for multiple liver metastases.Twenty -two courses of the folinic acid, 5-fluorouracil(5-FU)and oxaliplatin(FOLFOX4)/bevacizumab(BEV)regimen and 39 courses of 5 FU/Leucovorin/BEV were administered.Progressive splenomegaly and stomal varices were observed during the course of chemotherapy.The patient was admitted due to excessive bleeding after colostomy.Angiography revealed bleeding stomal varices secondary to portal hypertension.Splenectomy was performed with subsequent reduction in the size of the stomal varices and no rebleeding was observed.Oxaliplatin -based chemotherapy could lead to hepatic sinusoidal dilation and induce splenomegaly and varix formation secondary to portal hypertension.Our experience with this case suggests that careful attention should be paid to stomal varices in colostomy patients receiving oxaliplatin-based chemotherapy. PMID- 25131884 TI - [A case of squamous cell carcinoma of the nipple skin successfully treated with S 1 alone]. AB - Squamous cell carcinoma of the breast is uncommon, but that of the nipple skin is rarer. The effect of chemotherapy in these cases is yet to reach consensus. We report a rare case in which primary squamous cell carcinoma of the nipple skin was successfully treated with S-1 alone. A 64-year-old woman was admitted to our hospital because of a granulomatous tumor mass over the right nipple, which she was aware of for 10 years; the tumor showed a rapid increase in growth before admission. The tumor was approximately 4 cm at the first visit, and was diagnosed as squamous cell carcinoma by incisional biopsy. We administered preoperative systemic chemotherapy owing to the presence of metastasis in an axillary lymph node. After 2 courses of chemotherapy with oralS -1 at 100mg/day for 28 days followed by a 14-day resting period, the primary tumor and metastatic lymph node showed a remarkable reduction in size. The patient subsequently underwent a radical operation and is currently healthy without any recurrence. PMID- 25131886 TI - A cold-induced myo-inositol transporter-like gene confers tolerance to multiple abiotic stresses in transgenic tobacco plants. AB - A full length cDNA encoding a myo-inositol transporter-like protein, named as MfINT-like, was cloned from Medicago sativa subsp. falcata (herein falcata), a species with greater cold tolerance than alfalfa (M. sativa subsp. sativa). MfINT like is located on plasma membranes. MfINT-like transcript was induced 2-4 h after exogenous myo-inositol treatment, 24-96 h with cold, and 96 h by salinity. Given that myo-inositol accumulates higher in falcata after 24 h of cold treatment, myo-inositol is proposed to be involved in cold-induced expression of MfINT-like. Higher levels of myo-inositol was observed in leaves of transgenic tobacco plants overexpressing MfINT-like than the wild-type but not in the roots of plants grown on myo-inositol containing medium, suggesting that transgenic plants had higher myo-inositol transport activity than the wild-type. Transgenic plants survived better to freezing temperature, and had lower ion leakage and higher maximal photochemical efficiency of photosystem II (Fv /Fm ) after chilling treatment. In addition, greater plant fresh weight was observed in transgenic plants as compared with the wild-type when plants were grown under drought or salinity stress. The results suggest that MfINT-like mediated transport of myo-inositol is associated with plant tolerance to abiotic stresses. PMID- 25131888 TI - A systematic review of the demoralization syndrome in individuals with progressive disease and cancer: a decade of research. AB - CONTEXT: Demoralization can be understood as a condition that results from existential conflict. It presents with symptoms of hopelessness and helplessness caused by a loss of purpose and meaning in life. It is a significant mental health concern given there can be an associated desire for hastened death. OBJECTIVES: The aim of this systematic review was to synthesize the recent empirical evidence on demoralization in patients with progressive disease or cancer, including prevalence rates; the relationships between demoralization and sociodemographic, disease- and treatment-related, and psychological factors; and the psychometric properties of demoralization measures. METHODS: A comprehensive literature search using key words and subject headings was performed following PRISMA guidelines with nine electronic bibliographic databases, resulting in 25 studies (33 articles) with a total of 4545 participants reviewed. Full articles underwent methodological quality assessment, and correlational information was synthesized according to the strength of evidence. RESULTS: The findings suggest that demoralization is prevalent in patients with progressive disease or cancer and clinically significant in 13%-18%. A range of factors were consistently associated with demoralization: poorly controlled physical symptoms, inadequately treated depression and anxiety, reduced social functioning, unemployment, and single status. The Demoralization Scale has demonstrated good psychometric properties across five studies. CONCLUSION: Overall, this systematic review was limited by the extent of variability in the characteristics of studies. Patients who are single, isolated or jobless, have poorly controlled physical symptoms, or have inadequately treated anxiety and depressive disorders are at increased risk for demoralization. Clinical recognition of demoralization can trigger more focused interventions. PMID- 25131887 TI - Limits and responsibilities of physicians addressing spiritual suffering in terminally ill patients. AB - CONTEXT: Many patients experience spiritual suffering that complicates their physical suffering at the end of life. It remains unclear what physicians' perceived responsibilities are for responding to patients' spiritual suffering. OBJECTIVES: To investigate U.S. physician opinions about the impact patients' unresolved spiritual struggles have on their physical pain, physicians' responsibilities for treating patients' spiritual suffering compared with patients' physical pain, and the number of patients in the past 12 months whose suffering the physician was unable to relieve to an acceptable point. METHODS: The study was based on a mailed survey to 2016 practicing U.S. physicians from clinical specialties that care for significant numbers of dying patients. RESULTS: Of 1878 eligible physicians, 1156 (62%) responded. Most physicians agreed that patients with unresolved spiritual struggles tend to have worse physical pain (81%) and that physicians should seek to relieve patients' spiritual suffering just as much as patients' physical pain (88%). Compared with physicians who strongly disagreed that physicians should seek to relieve patients' spiritual suffering just as much as patients' physical pain, those who strongly agreed were less likely to report being unable to relieve patients' suffering to a point the physician found acceptable (27% vs. 54% reported three or more such patients in the previous 12 months, adjusted odds ratio [95% CI] = 0.3 [0.1, 0.8]). CONCLUSION: Most physicians believe that spiritual suffering tends to intensify physical pain and that physicians should seek to relieve such suffering. Physicians who believe they should address spiritual suffering just as much as physical pain report more success in relieving patient's suffering. PMID- 25131889 TI - Screening for depression in advanced disease: psychometric properties, sensitivity, and specificity of two items of the Palliative Care Outcome Scale (POS). AB - CONTEXT: Depression is common among patients with advanced disease but often difficult to detect. OBJECTIVES: To assess the Palliative care Outcome Scale (POS) (10 items) against the Geriatric Depression Scale (GDS)-10 total score and the Hospital Anxiety and Depression Scale (HADS)-Depression subscale total score and determine if the POS has appropriate items to screen for depression among people with advanced disease. METHODS: This was a secondary analysis performed on five studies. Four psychometric properties were assessed: data quality, scaling assumptions, acceptability, and internal consistency (reliability). Receiver operating characteristic (ROC) curves were used to determine the area under the curve. Sensitivity, specificity, positive and negative predictive values, false positive and negative rates, and positive and negative likelihood ratios were computed. RESULTS: The overall sample had 416 patients from Germany and England: 144 had cancer and 267 had nonmalignant conditions. Prevalence of depression across the sample was 17.5%. Floor and ceiling effects were rare. Cronbach's alpha coefficients for POS items 7 and 8 summed, GDS-10 and HADS-Depression items varied: 0.61 (heart failure) and 0.80 (cancer). Two items combined (Item 7 feeling depressed and Item 8-feeling good about yourself) consistently presented the highest area under the ROC curve, ranging from 0.76 (95% CI 0.60, 0.93) (Germany, lung cancer) to 0.97 (95% CI 0.91, 1.0) (heart failure), highest negative predictive value, and lowest false negative rate. For the overall sample, the cutoff 2/3 presented a negative predictive value of 89.4% (95% CI 84.7, 92.8) and false negative rate of 10.6 (95% CI 7.2, 15.3). CONCLUSION: POS items 7 and 8 summed are potentially useful to screen for depression in advanced disease populations. PMID- 25131890 TI - Rapid resolution of refractory chemotherapy-induced oral mucositis with platelet gel-released supernatant in a pediatric cancer patient: a case report. PMID- 25131891 TI - Avoidable and unavoidable visits to the emergency department among patients with advanced cancer receiving outpatient palliative care. AB - CONTEXT: Admissions to the emergency department (ED) can be distressing to patients with advanced cancer receiving palliative care. There is limited research about the clinical characteristics of these patients and whether these ED visits can be categorized as avoidable or unavoidable. OBJECTIVES: To determine the frequency of potentially avoidable ED visits (AvEDs) for patients with advanced cancer receiving outpatient palliative care in a large tertiary cancer center, identify the clinical characteristics of the patients receiving palliative care who visited the ED, and analyze the factors associated with AvEDs and unavoidable ED visits (UnAvEDs). METHODS: We randomly selected 200 advanced cancer patients receiving treatment in the outpatient palliative care clinic of a tertiary cancer center who visited the ED between January 2010 and December 2011. Visits were classified as AvED (if the problem could have been managed in the outpatient clinic or by telephone) or UnAvED. RESULTS: Forty-six (23%) of 200 ED visits were classified as AvED, and 154 (77%) of 200 ED visits were classified as UnAvED. Pain (71/200, 36%) was the most common chief complaint in both groups. Altered mental status, dyspnea, fever, and bleeding were present in the UnAvED group only. Infection, neurologic events, and cancer-related dyspnea were significantly more frequent in the UnAvED group, whereas constipation and running out of pain medications were significantly more frequent in the AvED group (P < 0.001). In a multivariate analysis, AvED was associated with nonwhite ethnicity (odds ratio [OR] 2.66; 95% CI 1.26, 5.59) and constipation (OR 17.08; 95% CI 3.76, 77.67), whereas UnAvED was associated with ED referral from the outpatient oncology or palliative care clinic (OR 0.24; 95% CI 0.06, 0.88) and the presence of baseline dyspnea (OR 0.46; 95% CI 0.21, 0.99). CONCLUSION: Nearly one-fourth of ED visits by patients with advanced cancer receiving palliative care were potentially avoidable. Proactive efforts to improve communication and support between scheduled appointments are needed. PMID- 25131892 TI - Doctors' decisions when faced with contradictory patient advance directives and health care proxy opinion: a randomized vignette-based study. AB - CONTEXT: Sometimes a written advance directive contradicts the opinion of a health care proxy. How this affects doctors' decision making is unknown. OBJECTIVES: To quantify the influence of contradictory instructions on doctors' decisions. METHODS: All the generalists and internists in French-speaking Switzerland were mailed the questionnaire. Respondents (43.5%) evaluated three vignettes that described medical decisions for incapacitated patients. Each vignette was produced in four versions: one with an advance directive, one with a proxy opinion, one with both, and one with neither (control). In the first vignette, the directive and proxy agreed on the recommendation to forgo a medical intervention; in the second, the advance directive opposed, but the proxy favored the intervention; and in the third, the roles were reversed. Each doctor received one version of each vignette, attributed at random. The outcome variables were the doctor's decision to forgo the medical intervention and the rating of the decision as difficult. RESULTS: Written advance directives and proxy opinions significantly influenced doctors' decision making. When both were available and concordant, they reinforced each other (odds ratio [OR] of forgoing intervention 35.7, P < 0.001 compared with no instruction). When the directive and proxy disagreed, the resulting effect was to forgo the intervention (ORs 2.1 and 2.2 for the two discordant vignettes, both P < 0.001). Discordance between instructions was associated with increased odds of doctors rating the decision as difficult (both ORs 2.0, P <= 0.001). CONCLUSION: Contradictions between advance directives and proxy opinions result in a weak preference for abstention from treatment and increase the difficulty of the decision. PMID- 25131893 TI - Dying in the hospital: what happens and what matters, according to bereaved relatives. AB - CONTEXT: Most deaths in Western countries occur in hospital, but little is known about factors determining the quality of dying (QOD). OBJECTIVES: The aim was to assess the QOD in hospital as experienced by relatives and identify factors related to QOD. METHODS: A cross-sectional study on 18 wards of a university hospital in The Netherlands was conducted, including relatives of patients who died after an admission of more than six hours, from June 2009 to March 2011. Relatives' perceptions of QOD and quality of care and the relation between dimensions of QOD and overall QOD scores were assessed. RESULTS: Two hundred forty-nine relatives participated (51%) and rated overall QOD at 6.3 (SD 2.7; range 0-10). According to relatives, patients suffered from 7.0 (SD 5.8) of 22 symptoms and were at peace with imminent death in 37%. Patients had been aware of imminent death in 26%, and relatives were aware in 49%. Furthermore, 39% of patients and 50% of relatives had said good-bye, and 77% of patients died in the presence of a relative. Symptom alleviation was sufficient in 53%, and in 75%, sufficient efforts had been made to relieve symptoms. Characteristics of QOD and quality of care could be summarized in nine domains, explaining 34% of the variation of QOD scores. Medical, personalized, and supportive care were most strongly related to QOD. CONCLUSION: Relatives rated QOD as sufficient. A majority of patients and relatives were not sufficiently prepared for imminent death, and relatives experienced many problems. QOD appears to be a multidimensional construct, strongly affected by medical care and staff attentiveness. PMID- 25131894 TI - Fipronil and imidacloprid reduce honeybee mitochondrial activity. AB - Bees have a crucial role in pollination; therefore, it is important to determine the causes of their recent decline. Fipronil and imidacloprid are insecticides used worldwide to eliminate or control insect pests. Because they are broad spectrum insecticides, they can also affect honeybees. Many researchers have studied the lethal and sublethal effects of these and other insecticides on honeybees, and some of these studies have demonstrated a correlation between the insecticides and colony collapse disorder in bees. The authors investigated the effects of fipronil and imidacloprid on the bioenergetic functioning of mitochondria isolated from the heads and thoraces of Africanized honeybees. Fipronil caused dose-dependent inhibition of adenosine 5'-diphosphate-stimulated (state 3) respiration in mitochondria energized by either pyruvate or succinate, albeit with different potentials, in thoracic mitochondria; inhibition was strongest when respiring with complex I substrate. Fipronil affected adenosine 5' triphosphate (ATP) production in a dose-dependent manner in both tissues and substrates, though with different sensitivities. Imidacloprid also affected state 3 respiration in both the thorax and head, being more potent in head pyruvate energized mitochondria; it also inhibited ATP production. Fipronil and imidacloprid had no effect on mitochondrial state-4 respiration. The authors concluded that fipronil and imidacloprid are inhibitors of mitochondrial bioenergetics, resulting in depleted ATP. This action can explain the toxicity of these compounds to honeybees. PMID- 25131896 TI - Tactics for teaching evidence-based practice: improving self-efficacy in finding and appraising evidence in a master's evidence-based practice unit. AB - This column shares the best evidence-based strategies and innovative ideas on how to facilitate the learning of EBP principles and processes by clinicians as well as nursing and interprofessional students. Guidelines for submission are available at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741-6787. PMID- 25131897 TI - Cascade sensing of gold and thiols with imidazole-bearing functional porphyrins. AB - An imidazole-bearing zinc porphyrin (PZn) has been designed for the selective detection of Au(3+), and the porphyrin and gold complex (PZn.Au(3+)) can additionally be used to identify gold-binding functional groups such as cysteine residues and other mercaptans. PMID- 25131898 TI - Assisted reproduction: Ethical and legal issues. AB - Since inception, the use of assisted reproductive technologies (ART) has been accompanied by ethical, legal, and societal controversies. Guidelines have been developed to address many of these concerns; however, the rapid evolution of ART requires their frequent re-evaluation. We review the literature on ethical and legal aspects of ART, highlighting some of the most visible and challenging topics. Of specific interest are: reporting of ART procedures and outcomes; accessibility to ART procedures; issues related to fertility preservation, preimplantation genetic testing, gamete and embryo donation, and reproductive outcomes after embryo transfer. Improvements in ART reporting are needed nationally and worldwide. Reporting should include outcomes that enable patients to make informed decisions. Improving access to ART and optimizing long-term reproductive outcomes, while taking into account the legal and ethical consequences, are challenges that need to be addressed by the entire community of individuals involved in ART with the assistance of bioethicists, legal counselors, and members of society in general. PMID- 25131899 TI - Geographical comparisons of information and support needs of Australian women following the primary treatment of breast cancer: a 10-year replication study. AB - BACKGROUND: In 2002, Raupach and Hiller examined the use of and satisfaction with information and support following treatment of breast cancer from a sample of participants in South Australia. In 2013 this study was replicated to include participants Australia wide and analyse comparisons based on geographical location. Statistical comparisons with the original study were also conducted. DESIGN: A 10 year replication study using a cross-sectional needs analysis survey. SETTING AND PARTICIPANTS: Women aged 18+ years diagnosed with breast cancer between 6 and 30 months ago were sourced from two national databases of women diagnosed with breast cancer. RESULTS: A total of 325 participants completed the survey. The Internet was the most commonly used source of information with 70% (n = 229 of 325) of women using the internet for information, a statistically significantly higher percentage compared with the 2002 study. The study found the top four information issues rated as moderately/extremely important by women in 2013 were identical in 2002. A comparison of sources of support used showed that women in outer regional, remote and very remote areas were statistically more likely to use the breast care nurse (BCN) for support (P = 0.044). CONCLUSIONS: The study provides useful, up-to-date data about information and support services used by Australian women with breast cancer. Comparisons with the earlier study show some of the needs of women have changed over time, but others have remained the same. Geographic comparisons overall, demonstrate many consistent findings regardless of location, however, the important work of the breast care nurse is an area in need of further research. PMID- 25131900 TI - Effects of salpingectomy and antituberculosis treatments on fertility results in patients with genital tuberculosis. AB - AIM: The aim of this study was to demonstrate the effects of tubal surgery and antituberculosis treatments in patients with genital tuberculosis. MATERIAL AND METHODS: A total of 38 infertile women who had been diagnosed with pelvic tuberculosis and who had had laparoscopy and hysteroscopy were recruited into the study. All women with female genital tuberculosis were divided into two groups: group 1 (salpingectomized, n=21) and group 2 (not salpingectomized, n=15). Both of the groups were treated with antitubercular therapy for 6-12 months. RESULTS: There was no significant difference in level of gonadotrophins used, estradiol levels on human chorionic gonadotrophin day, mean and mature oocytes retrieved, mean embryos transferred, or cancellation and fertilization rates. Only the number of days of stimulation was statistically significantly higher in group 1 compared to group 2 (10.4+/-2.3 vs 9.2+/-1.8; P=0.048). Although it did not reach the statistically significant level, clinical pregnancy rate was higher in group 1 (37.5%, 12/32 vs 23.8%, 5/21; P=0.306). Although not statistically significant, number of ongoing pregnancies per embryo transfer, spontaneous abortion rates before 20 weeks of gestation and take-home baby rates were higher in group 1 compared to group 2 (15.5%, 12/77 vs 6.6%, 3/45; P=0.150; 28.1%, 9 vs 23.8%, 5; P=0.600; 9%, 3 vs 0; P=0.160, respectively). CONCLUSION: Salpingectomy is an option for treatment in patients diagnosed with pelvic tuberculosis and infertility to improve both clinical pregnancy rates and take-home baby rates in patients treated with antituberculosis therapy for 12 months. PMID- 25131895 TI - The interferon regulatory factors as novel potential targets in the treatment of cardiovascular diseases. AB - The family of interferon regulatory factors (IRFs) consists of nine members (IRF1 IRF9) in mammals. They act as transcription factors for the interferons and thus exert essential regulatory functions in the immune system and in oncogenesis. Recent clinical and experimental studies have identified critically important roles of the IRFs in cardiovascular diseases, arising from their participation in divergent and overlapping molecular programmes beyond the immune response. Here we review the current knowledge of the regulatory effects and mechanisms of IRFs on the immune system. The role of IRFs and their potential molecular mechanisms as novel stress sensors and mediators of cardiovascular diseases are highlighted. PMID- 25131902 TI - Rhizosphere effect and salinity competing to shape microbial communities in Phragmites australis (Cav.) Trin. ex-Steud. AB - Rhizobacterial communities associated with Phragmites australis (Cav.) Trin. ex Steud. in a hypersaline pond close to Wuliangsuhai Lake (Inner Mongolia - China) were investigated and compared with the microbial communities in bulk sediments of the same pond. Microbiological analyses have been done by automated ribosomal intergenic spacer analysis (ARISA) and partial 16S rRNA gene 454 pyrosequencing. Although community richness was higher in the rhizosphere samples than in bulk sediments, the salinity seemed to be the major factor shaping the structure of the microbial communities. Halanaerobiales was the most abundant taxon found in all the different samples and Desulfosalsimonas was observed to be present more in the rhizosphere rather than in bulk sediment. PMID- 25131901 TI - Burden of epilepsy in rural Kenya measured in disability-adjusted life years. AB - OBJECTIVES: The burden of epilepsy, in terms of both morbidity and mortality, is likely to vary depending on the etiology (primary [genetic/unknown] vs. secondary [structural/metabolic]) and with the use of antiepileptic drugs (AEDs). We estimated the disability-adjusted life years (DALYs) and modeled the remission rates of active convulsive epilepsy (ACE) using epidemiologic data collected over the last decade in rural Kilifi, Kenya. METHODS: We used measures of prevalence, incidence, and mortality to model the remission of epilepsy using disease modeling software (DisMod II). DALYs were calculated as the sum of Years Lost to Disability (YLD) and Years of Life Lost (YLL) due to premature death using the prevalence approach, with disability weights (DWs) from the 2010 Global Burden of Disease (GBD) study. DALYs were calculated with R statistical software with the associated uncertainty intervals (UIs) computed by bootstrapping. RESULTS: A total of 1,005 (95% UI 797-1,213) DALYs were lost to ACE, which is 433 (95% UI 393-469) DALYs lost per 100,000 people. Twenty-six percent (113/100,000/year, 95% UI 106-117) of the DALYs were due to YLD and 74% (320/100,000/year, 95% UI 248 416) to YLL. Primary epilepsy accounted for fewer DALYs than secondary epilepsy (98 vs. 334 DALYs per 100,000 people). Those taking AEDs contributed fewer DALYs than those not taking AEDs (167 vs. 266 DALYs per 100,000 people). The proportion of people with ACE in remission per year was estimated at 11.0% in males and 12.0% in females, with highest rates in the 0-5 year age group. SIGNIFICANCE: The DALYs for ACE are high in rural Kenya, but less than the estimates of 2010 GBD study. Three-fourths of DALYs resulted from secondary epilepsy. Use of AEDs was associated with 40% reduction of DALYs. Improving adherence to AEDs may reduce the burden of epilepsy in this area. PMID- 25131903 TI - Appetite predicts mortality in free-living older adults in association with dietary diversity. A NAHSIT cohort study. AB - This study aimed to assess the predictive ability of appetite for mortality among representative free-living Taiwanese older adults. A total of 1856 participants aged 65 years or over from the Elderly Nutrition and Health Survey during 1999 2000 completed an appetite question in a larger questionnaire. Personal information was obtained by face-to-face interview at baseline, together with a 24-hour dietary recall and simplified food frequency questionnaire which provided a dietary diversity score and food intake frequency. Survivorship was ascertained from the Death Registry until December 31, 2008. Participants with a poor appetite had lower dietary diversity scores (DDS) and intake frequencies of meat, fish and sea food, egg, vegetable and fruit intake, along with lower energy, protein, vitamin B-1, niacin, iron and phosphate intakes. Those who had fair and poor appetites had a higher risk of all-cause mortality compared to those with good appetite, with hazard ratios (HR) (95% confidence interval, CI) of 1.28 (1.03-1.58) and 2.27 (1.71-3.02), respectively. After adjustment for confounders, the HRs (95% CI) were 1.05 (0.83-1.33) and 1.50 (1.03-2.18), respectively. With further adjustment for DDS or general health these HRs became non-significant. The joint HR (95% CI) for "DDS <= 4 and poor appetite" was 1.77 (1.04-3.00) compared to "DDS > 4 and good appetite" as referent. Poor appetite is associated with lower food and nutrient intakes and an independent risk for mortality in older Taiwanese. In conclusion, appetite is separate, mediated by general health and modulated by dietary quality in its predictive capacity for mortality. PMID- 25131904 TI - Relationship between mouthful volume and number of chews in young Japanese females. AB - OBJECTIVE: Modification of eating behavior in Japan is promoted to prevent overweight and obesity, but the effects of such modifications are unclear. This study aimed to clarify the inter- and intra-individual relationship between bite size and number of chews of food. DESIGN AND METHODS: Subjects comprised of 50 young healthy Japanese women (mean age 19.5 years). Food materials were boiled rice and apple. First, the average bite size and the number of chews per mouthful of food were calculated across the study cohort. The number of chews was counted by the subjects themselves and then self-reported. Correlation between the individual one-bite volume and the number of chews per volume was analyzed using Spearman's rank correlation coefficient. Second, the number of chews for three different sized bites of food (half of one bite, one bite, and one-and-a-half bites) were calculated as a prospective observational study. The number of chews for each of the three volumes of food was compared using one way ANOVA with Bonferroni correction. RESULTS: For both food types, there was a negative correlation between individual mouthful volume and number of chews for both food materials. The number of chews per volume decreased as bite sizes increased. CONCLUSION: This study demonstrated an inter- and intra-individual relationship between bite size and the number of chews and suggested that smaller bite sizes were associated with more chews per volume of food. PMID- 25131905 TI - Impact of clinical and echocardiographic characteristics on occurrence of cardiac events in cardiac amyloidosis as proven by endomyocardial biopsy. AB - BACKGROUND: Although patients with immunoglobulin light chain (AL) cardiac amyloidosis exhibit worse outcomes than those with transthyretin (TTR) cardiac amyloidosis, few data exist regarding the occurrence of cardiac events and the echocardiographic indices in endomyocardial biopsy (EMBx) proven amyloidosis. METHODS: From November 2007 to October 2012, we identified 33 patients with EMBx proven amyloidosis. There were 12 patients (8 men; mean age: 66 years) with AL and 21 patients (20 men; mean age: 78 years) with TTR. We performed serial echocardiography and observed the patients during follow-up; defining all-cause mortality as the primary endpoint and hospitalization for heart failure as the secondary endpoint. RESULTS: The survival rates at 12 months were 20.8% and 85.7% in AL and TTR, respectively (p<0.001). The cumulative incidences of the composite of death or readmission for heart failure at 12 months were 91.7% and 51.3% in AL and TTR, respectively (p<0.001). A multivariate analysis showed that the AL type amyloid was the powerful predictor of mortality (hazard ratio: 8.50, 95% confidence interval: 1.79 to 40.57, p<0.05). Under these conditions, the E/e' in AL tended to increase from 23+/-13 to 28+/-11 (p=0.06) with marked increases in B type natriuretic peptide (779+/-456 pg/ml to 1576+/-895 pg/ml, p<0.05), although these remained unchanged in TTR, which exhibited significantly increased left ventricular end-diastolic dimensions from 40+/-4 mm to 42+/-4 mm (p<0.05). CONCLUSIONS: The survival rate was generally worse in AL cardiac amyloidosis, although the readmission for heart failure remains high in TTR cardiac amyloidosis with the occurrence of left ventricular dilatation. PMID- 25131906 TI - A systematic review of clozapine induced cardiomyopathy. AB - BACKGROUND: Clozapine is a unique anti-psychotic medication that is most effective in the treatment of refractory schizophrenia and reducing suicidality. Cardiomyopathy is among the side effects of this medication that limits its use. There are a number of case reports, case series and expert opinion papers discussing clozapine induced cardiomyopathy, but there is no evidence-based review of the subject to guide clinicians. METHODS: We undertook a systematic review of the literature on cardiomyopathy associated with clozapine. The primary systemic search was in MEDLINE but EMBASE, PsycINFO, and Cochrane were searched and manufacturers of clozapine were contacted for cases. Articles were then individually reviewed to find additional reports. RESULTS: We identified 17 articles detailing 26 individual cases and 11 additional articles without individual case data. The mean age at time of diagnosis was 33.5 years. The mean dose of clozapine on presentation was 360 mg. Symptoms developed at an average of 14.4 months after initiating clozapine. The clinical presentation was generally consistent with heart failure: including shortness of breath (60%) and palpitations (36%). Echocardiography at presentation showed dilated cardiomyopathy in 39% of cases and was not specified in other cases. CONCLUSION: There should be a low threshold in performing echocardiography in suspected cases of clozapine induced cardiomyopathy. Clozapine should be withheld in the setting of cardiomyopathy without other explanation. There is limited data on the safety of drug re-challenge in clozapine induced cardiomyopathy. Re-challenge may be considered in carefully selected cases but close monitoring and frequent echocardiography are required. PMID- 25131907 TI - Response to the letter of Mynard and Smolich. PMID- 25131908 TI - Retinal vessel analysis and heart rate variability. PMID- 25131909 TI - Effectiveness of the combination therapy with lisinopril, ivabradine and multivitamin supplementation in anthracycline-induced severe cardiotoxicity. PMID- 25131910 TI - Hemoglobin and renal replacement therapy after cardiopulmonary bypass surgery: a predictive score from the Cardiac Surgery Registry of Puglia. AB - BACKGROUND: Acute Kidney Injury (AKI) after cardiac surgery is a complication influencing postoperative outcome. Preoperative hemoglobin is a predictor of postoperative AKI. We aimed to identify preoperative predictors of Renal Replacement Therapy (RRT) and to develop a new risk-scoring system including hemoglobin to better stratify the risk of events. METHODS: We evaluated 3288 consecutive patients of the Regional Cardiac Surgery Registry of Puglia operated in 2011-2012. Chronic dialysis and renal transplantation patients were excluded. Primary outcome was post-operative RRT incidence. RESULTS: The study sample was divided in two cohorts: 1642 patients (70 RRT) operated during the year 2011 as derivation cohort and 1646 patients (69 RRT) of the year 2012 as validation. In a multivariable logistic regression model using a stepwise method, six preoperative risk factors were associated with RRT in the derivation cohort: creatinine clearance, preoperative hemoglobin, neurological dysfunction, left ventricular ejection fraction, urgency and combined procedures (discrimination c-index 0.844 and 0.818 in the validation cohort). Scoring system included risk factors obtained from derivation cohort adjusting their relative weight with updated rounded coefficients in the validation cohort: creatinine clearance<50ml/min (1 point), hemoglobin<=12.5g/dl (1 point), left ventricular ejection fraction<=30% (1 point), urgent operation (1 point), emergency-salvage surgery (2 points), and combined procedures (1 point). In both cohorts, outcomes were strongly correlated with score points. CONCLUSIONS: Our simple bedside prognostic score demonstrates good performance in predicting RRT. Hemoglobin plays an important role and future studies will clarify if preoperative anemia correction will lead to decreased RRT risk. PMID- 25131911 TI - Postconditioning or preconditioning, which should be promoted for protecting from ischemic reperfusion injury? Response to letter IJC-D-14-02875. PMID- 25131912 TI - ERBB1/EGFR and ERBB2 (HER2/neu)--targeted therapies in cancer and cardiovascular system with cardiovascular drugs. PMID- 25131913 TI - Detailed-comparison of average journal-impact-factors of oral and poster abstracts presented at scientific-session that achieved publication at 2009 Radiological-Society of North-America Scientific-Assembly and Annual Meeting including cardiac-session. PMID- 25131914 TI - Lead extraction in a young girl with dehiscence of a pacemaker implanted in the subpectoral region. PMID- 25131915 TI - Assessment of the source of ischemic cerebrovascular events in patients with Chagas disease. PMID- 25131916 TI - Assessment of left coronary artery-to-left ventricle fistulae with left ventricular non-compaction by multimodality imaging in a child. PMID- 25131917 TI - Tacrolimus-induced left ventricular apical hypertrophy in a patient with post allogeneic hematopoietic stem cell transplantation. PMID- 25131918 TI - Inverse relationship between raft LRP1 localization and non-raft ERK1,2/MMP9 activation in idiopathic dilated cardiomyopathy: potential impact in ventricular remodeling. AB - BACKGROUND: Idiopathic dilated cardiomyopathy (IDCM) is characterized by adverse ventricular remodeling attributed to altered activity of extracellular matrix metalloproteinase (MMP). MMP overactivation is linked to changes in extracellular signal-regulated kinases (ERK), reportedly modulated by the low-density lipoprotein receptor-related protein 1 (LRP1) receptor. The aim of this work was to compare the levels, membrane distribution and interactions of LRP1, ERK1,2 and MMP2/9 in control and IDCM myocardium. METHODS: Left ventricle samples from IDCM patients and control subjects were collected to analyze gene and protein expression by Real-time PCR and Western blot, respectively. Fractions enriched in cholesterol, Flotillin-1 and Caveolin-3 (rafts) were isolated from the remaining membrane (non-rafts) by sucrose gradient ultracentrifugation. We assessed the formation of LRP1-ERK1,2 complexes and MMP activity by immunoprecipitation and zymography, respectively. RESULTS: In control myocardium, LRP1 was exclusively found in non-rafts while activation of ERK1,2 was preferentially detected in rafts. LRP1/p-ERK1,2 complexes were almost undetectable in rafts and non-rafts. In contrast, in IDCM myocardium, LRP1 moved to rafts and ERK1,2 activation was found in raft and non-raft fractions. Moreover, LRP1/p-ERK1,2 complexes were also found in both membrane fractions, although the amount was higher in non-rafts where MMP9 overactivation was exclusively detected. CONCLUSIONS: The presented findings demonstrate a differential membrane compartmentalisation of ERK signaling in IDCM myocardium. The movement of LRP1 to rafts and the concomitant increase in non-raft-related ERK1,2/MMP9 activation may have crucial clinical implications in the progression of disease. PMID- 25131919 TI - Cardiovascular mortality in hypertensive patients newly prescribed perindopril vs. lisinopril: a 5-year cohort study of 15,622 Chinese subjects. AB - BACKGROUND: Perindopril and lisinopril are two common ACE inhibitors prescribed for management of hypertension. Few studies have evaluated their comparative effectiveness to reduce mortality. This study compared the all-cause and cardiovascular related mortality among patients newly prescribed ACE inhibitors. METHODS: All adult patients newly prescribed perindopril or lisinopril from 2001 to 2005 in all public clinics or hospitals in Hong Kong were retrospectively evaluated, and followed up until 2010. Patients prescribed the ACE inhibitors for less than a month were excluded. The all-cause mortality and cardiovascular specific (i.e. coronary heart disease, heart failure and stroke) mortality were compared. Cox proportional hazard regression model was used to assess the mortality, controlling for age, sex, socioeconomic status, patient types, the presence of comorbidities, and medication adherence as measured by the proportion of days covered. An additional model using propensity scores was performed to minimize indication bias. RESULTS: A total of 15,622 patients were included in this study, in which 6910 were perindopril users and 8712 lisinopril users. The all-cause mortality (22.2% vs. 20.0%, p<0.005) and cardiovascular mortality (6.5% vs. 5.6%, p<0.005) were higher among lisinopril users than perindopril users. From regression analyses, lisinopril users were 1.09-fold (95% C.I. 1.01-1.16) and 1.18-fold (95% C.I. 1.02-1.35) more likely to die from any-cause and cardiovascular diseases, respectively. Age-stratified analysis showed that this significant difference was observed only among patients aged >70 years. The additional models controlled for propensity scores yielded comparable results. CONCLUSIONS: The long-term all-cause and cardiovascular related mortality rates of lisinopril users was significantly different from those of perindopril users. These findings showed that intra-class variation on mortality exists among ACE inhibitors among those aged 70 years or older. Future studies should consider a longer, large-scale randomized controlled trial to compare the effectiveness between different medications in the ACEI class, especially among the elderly. PMID- 25131921 TI - Cancer multidrug resistance-targeted therapy in both cancer and cardiovascular system with cardiovascular drugs. PMID- 25131920 TI - Three-dimensional aortic root reconstruction derived from rotational angiography for transcatheter balloon-expandable aortic valve implantation guidance. PMID- 25131922 TI - Inferior vena cava filters in the United States: less is more. AB - Despite the widespread use of Inferior vena cava (IVC) filters, there is no quality evidence to demonstrate their efficacy for routine use, nor there is a consensus on their appropriate indications among major medical societies. The introduction of retrievable filters led to further increase in the utilization of these devices. However, several studies have shown that retrievable filters are rarely retrieved. The implant rates of IVC filters are many folds higher in the United States than in Europe, yet the retrieval rates are much lower. The U.S. Food and Drug Administration has recently issued a safety alert advocating for consideration of filter retrieval when the protection offered by the filter is no longer needed. The controversies surrounding IVC filter placement and retrieval, however, will likely to continue in the absence of good evidence on their efficacy and side effects. Time has come for initiatives to conduct well designed trials based on agreed-upon criteria to settle this debate. PMID- 25131923 TI - PTX3: a modulator of human coronary plaque vulnerability acting by macrophages type 2. AB - BACKGROUND: Acute myocardial infarction (AMI), is related to a diffuse active inflammation of the coronary tree associated with rupture of one of the multiple vulnerable plaques. The presence of soluble mediators of inflammation with their synergic or antagonistic actions coordinates the physiological response determining the plaque fate and the fatal event. The present study focus on the cytokines network operating in human coronary plaques of patients died from AMI and controls, pointing out that coronaries of AMI patients produce PTX3 protein twice as that of controls and express high level of PTX3 mRNA. RESULTS: The presence of CX3CR1 polymorphisms is significantly correlated with the incidence and the outcome of acute myocardial infarction inducing in the whole coronary tree a strong recruitment of Th1 polarized inflammation that is directly correlated to PTX3 expression. CONCLUSIONS: Moreover we found a positive correlation between the expression of PTX3 in the plaque and the content of macrophage cells showing a M2 polarization indicating the possible role of this chemokine as mediator of immune response that would orchestrate plaque evolution and inflammatory cell type activation. PMID- 25131924 TI - MicroRNA-29b promotes high-fat diet-stimulated endothelial permeability and apoptosis in apoE knock-out mice by down-regulating MT1 expression. AB - BACKGROUND: High-fat diet has been reported to be associated with cardiovascular diseases which is implicated in atherosclerosis. However, the underlying mechanisms remain unknown. MicroRNAs (miRNAs) are non-coding small RNAs that control gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to be involved in atherosclerosis. METHODS AND RESULTS: This study examined whether microRNA-29b (miR-29b) regulates high-fat diet induced endothelial permeability and apoptosis by targeting MT1, a known melatonin membrane receptor. In apoE knock-out mice, a high-fat diet increased miR-29b expression and induced apoptosis as determined by up-regulation of caspase-3 activity. However, a standard diet did not alter apoptosis. miR-29b antagomir decreased endothelial permeability and apoptosis in high-fat diet-stimulated mice. In contrast, a miR-29b mimic enhanced endothelial permeability and apoptosis. The induction of miR-29b correlated with a reduction in Bcl-2 and MT1 in high-fat diet-stimulated mice. miR-29b have an effect on the marker of inflammation (NF-kappaB) and cell adhesion molecule (ICAM-1). We further showed that miR-29b targeted and inhibited MT1 expression through a target site located in the 3'un-translational region of MT1 mRNA. This study demonstrates a role of miR-29b in atherosclerosis and identifies MT1 as a direct target of miR-29b. CONCLUSIONS: The effect of miR-29b on endothelial permeability and apoptosis is mediated through the down-regulation of MT1. Thus, miR-29b may be a new therapeutic target for atherosclerosis. PMID- 25131925 TI - Resource use and cost implications of implementing a heart failure program for patients with systolic heart failure in Swedish primary health care. AB - AIM: Heart failure (HF) is a common but serious condition which involves a significant economic burden on the health care economy. The purpose of this study was to evaluate cost and quality of life (QoL) implications of implementing a HF management program (HFMP) in primary health care (PHC). METHODS AND RESULTS: This was a prospective randomized open-label study including 160 patients with a diagnosis of HF from five PHC centers in south-eastern Sweden. Patients randomized to the intervention group received information about HF from HF nurses and from a validated computer-based awareness program. HF nurses and physicians followed the patients intensely in order to optimize HF treatment according to current guidelines. The patients in the control group were followed by their regular general practitioner (GP) and received standard treatment according to local management routines. No significant changes were observed in NYHA class and quality-adjusted life years (QALY), implying that functional class and QoL were preserved. However, costs for hospital care (HC) and PHC were reduced by EUR 2167, or 33%. The total cost was EUR 4471 in the intervention group and EUR 6638 in the control group. CONCLUSIONS: Introducing HFMP in Swedish PHC in patients with HF entails a significant reduction in resource utilization and costs, and maintains QoL. Based on these results, a broader implementation of HFMP in PHC may be recommended. However, results should be confirmed with extended follow-up to verify long-term effects. PMID- 25131926 TI - Superior vena cava obstruction as late complication of biventricular pacemaker implantation: surgical replacement of the malfunctioning previous leads. PMID- 25131927 TI - Assessment of coronary collateral artery by CT angiography in patients with ST elevation acute myocardial infarction. PMID- 25131928 TI - Severe autonomic failure as a predictor of mortality in aortic valve stenosis. AB - BACKGROUND: Identification of new risk markers in aortic valve stenosis (AS) is of great interest. Here, we hypothesized that the presence of severe autonomic failure (SAF) is an important prognostic marker in both, symptomatic patients undergoing invasive treatment for severe AS, and in asymptomatic patients with severe AS who were primarily treated conservatively. METHODS: We prospectively enrolled 300 patients with severe AS (aortic valve area<1.0 cm2 or mean aortic gradient>40 mmHg) in sinus rhythm. All patients underwent a 24-h Holter recording for assessment of heart rate turbulence (HRT) and deceleration capacity (DC). Patients with both, abnormal DC and HRT were considered to suffer from SAF. RESULTS: The first hypothesis was tested in 216 symptomatic patients who underwent successful aortic valve replacement (AVR) or transcatheter aortic valve implantation (TAVI). During follow-up of 2 years, 29 of these patients died. SAF was the strongest independent predictor of mortality (hazard ratio 5.6, 95% confidence interval 2.6-12.0; p<0.001) with 2-year mortality rates of 50.0% and 10.7% in SAF-positive and SAF-negative patients, respectively (p<0.001). The second hypothesis was tested in 71 patients, who were asymptomatic at study entry and for whom a primarily conservative treatment strategy was proposed. During follow-up, 10 of these patients died. SAF also predicted death in asymptomatic patients with 2-year mortality rates of 52.4% and 8.7% in SAF-positive and SAF negative patients, respectively (p=0.010). CONCLUSIONS: SAF is a strong and independent predictor of mortality in symptomatic and asymptomatic patients with severe AS. PMID- 25131929 TI - Localization of amyloid beta (Abeta1-42) protofibrils in membrane lateral compartments: effect of cholesterol and 7-Ketocholesterol. AB - Cholesterol plays an important role in the interaction of Alzheimer's amyloid beta (Abeta) with cell membranes, an important event in Abeta-induced cytotoxicity. However, it is not fully understood how cholesterol influences the association of Abeta with membrane lateral compartments. We have shown that by modulating membrane fluidity, cholesterol decreased peptide localization in solid ordered domains and increased that in liquid-ordered domains. It changed the amount of Abeta associating with liquid-disordered (Ld) phase with different tendencies depending on the composition of heterogeneous membrane systems. 7 Ketocholesterol, an oxidized derivative of cholesterol, majorly enhanced the fluidity of and Abeta interaction with Ld phase. These findings are useful for clarifying the impact of cholesterol and its oxidation in Abeta-induced toxicity. PMID- 25131931 TI - MiR-605 represses PSMD10/Gankyrin and inhibits intrahepatic cholangiocarcinoma cell progression. AB - The aberrant expression of PSMD10 has important functions in various malignancies. This study showed that PSMD10 was highly expressed and inversely correlated with the expression of miR-605 in intrahepatic cholangiocarcinoma (ICC) specimens. MiR-605 directly targeted and repressed PSMD10 expression. In addition, over-expression of miR-605 inhibited ICC cell progression both in vitro and in vivo. This effect of miR-605 on ICC cells was similar to that of PSMD10 knock-down by RNAi. Moreover, restoration of PSMD10 could reverse the phenotypic alteration caused by miR-605 in ICC cells. These results suggest a new therapeutic strategy in ICC by restoring miR-605, which is regulated by p53. PMID- 25131930 TI - Hepatitis C virus core protein enhances HIV-1 replication in human macrophages through TLR2, JNK, and MEK1/2-dependent upregulation of TNF-alpha and IL-6. AB - Despite their differential cell tropisms, HIV-1 and HCV dramatically influence disease progression in coinfected patients. Macrophages are important target cells of HIV-1. We hypothesized that secreted HCV core protein might modulate HIV 1 replication. We demonstrate that HCV core significantly enhances HIV-1 replication in human macrophages by upregulating TNF-alpha and IL-6 via TLR2-, JNK-, and MEK1/2-dependent pathways. Furthermore, we show that TNF-alpha and IL-6 secreted from HCV core-treated macrophages reactivates monocytic U1 cells latently infected with HIV-1. Our studies reveal a previously unrecognized role of HCV core by enhancing HIV-1 infection in macrophages. PMID- 25131932 TI - Paired related homeobox protein-like 1 (Prrxl1) controls its own expression by a transcriptional autorepression mechanism. AB - The homeodomain factor paired related homeobox protein-like 1 (Prrxl1) is crucial for proper assembly of dorsal root ganglia (DRG)-dorsal spinal cord (SC) pain sensing circuit. By performing chromatin immunoprecipitation with either embryonic DRG or dorsal SC, we identified two evolutionarily conserved regions (i.e. proximal promoter and intron 4) of Prrxl1 locus that show tissue-specific binding of Prrxl1. Transcriptional assays confirm the identified regions can mediate repression by Prrxl1, while gain-of-function studies in Prrxl1 expressing ND7/23 cells indicate Prrxl1 can down-regulate its own expression. Altogether, our results suggest that Prrxl1 uses distinct regulatory regions to repress its own expression in DRG and dorsal SC. PMID- 25131933 TI - A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver. AB - Identification of microRNAs (miRNAs) that regulate lipid metabolism is important to advance the understanding and treatment of some of the most common human diseases. In the liver, a few key miRNAs have been reported that regulate lipid metabolism, but since many genes contribute to hepatic lipid metabolism, we hypothesized that other such miRNAs exist. To identify genes repressed by miRNAs in mature hepatocytes in vivo, we injected adult mice carrying floxed Dicer1 alleles with an adenoassociated viral vector expressing Cre recombinase specifically in hepatocytes. By inactivating Dicer in adult quiescent hepatocytes we avoided the hepatocyte injury and regeneration observed in previous mouse models of global miRNA deficiency in hepatocytes. Next, we combined gene and miRNA expression profiling to identify candidate gene/miRNA interactions involved in hepatic lipid metabolism and validated their function in vivo using antisense oligonucleotides. A candidate gene that emerged from our screen was lipoprotein lipase (Lpl), which encodes an enzyme that facilitates cellular uptake of lipids from the circulation. Unlike in energy-dependent cells like myocytes, LPL is normally repressed in adult hepatocytes. We identified miR-29a as the miRNA responsible for repressing LPL in hepatocytes, and found that decreasing hepatic miR-29a levels causes lipids to accumulate in mouse livers. CONCLUSION: Our screen suggests several new miRNAs are regulators of hepatic lipid metabolism. We show that one of these, miR-29a, contributes to physiological lipid distribution away from the liver and protects hepatocytes from steatosis. Our results, together with miR-29a's known antifibrotic effect, suggest miR-29a is a therapeutic target in fatty liver disease. PMID- 25131935 TI - In vitro combined treatment with cetuximab and trastuzumab inhibits growth of colon cancer cells. AB - OBJECTIVES: Overexpression or constitutive activation of epidermal growth factor receptors (EGFR) is involved in growth of human cancers. We investigated effects of EGFR and HER-2 blockade in colon cancer cell lines using cetuximab and trastuzumab, with the aim of developing novel approaches to cancer therapy. MATERIALS AND METHODS: We studied effects of treatment on cell growth, cell cycle distribution, induction of apoptosis, changes in EGFR and HER-2 mRNA-protein expression and EGFR and HER-2 gene copy number in Caco-2, HT-29 and HCT-116 cells. RESULTS: Treatment of cells resulted in no effect in one of the three cell lines and in inhibition of cell proliferation in a time- and dose-dependent manner in the other two, with modulation of EGFR and HER-2 mRNA and protein levels. Differences in sensitivity to cetuximab and trastuzumab were observed. Treatment induced specific changes in cell cycle distribution in both cell lines affected, while apoptosis was not increased. Fluorescence in situ hybridization analysis revealed abnormal copy number of two genes resulting from aneuploidy; this was not responsible for different sensitivity to combination between the two cell lines. CONCLUSIONS: Targeting EGFR and HER-2 simultaneously could have useful applications in colorectal cancer treatment. To improve pharmacological efficacy of cetuximab and trastuzumab combination, molecular mechanisms involved in their activity need to be elucidated. PMID- 25131937 TI - Protective effect of the herbal preparation, STW 5, against intestinal damage induced by gamma radiation in rats. AB - PURPOSE: STW 5 (marketed as Iberogast((r)), Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) is a herbal preparation reported to possess anti-inflammatory properties and antioxidant activity. We investigated the effect of STW 5 against intestinal injury induced after whole body exposure to ionizing radiation (IR). MATERIALS AND METHODS: Intestinal mucositis was induced in rats by irradiation at a level of 6 Gy. STW 5 (5 ml/kg) was delivered orally for 5 days before irradiation and 2 days after. Rats were sacrificed, jejunum homogenates were tested to assess biochemical parameters indicating intestinal injury and jejunum segments were exposed to semi-quantitative histological examination. RESULTS: IR led to an increase in overall damage severity (ODS) score associated with a significant rise in tumor necrosis factor (TNF-alpha) and thiobarbituric acid reactive substances (TBARS) by 46% and 50% (p <= 0.05), respectively, whereas the reduced glutathione (GSH), sucrase and alkaline phosphatase enzyme activities were significantly decreased by 68%, 76% and 25% (p <= 0.05), respectively, in intestinal homogenates. IR led to a reduction of plasma citrulline. Pre-treatment with STW 5 guarded against the changes in ODS score and in all parameters measured. CONCLUSION: Pre-treatment with STW 5 has the potential to decrease the severity of radiation-induced mucositis. PMID- 25131934 TI - Transplantation of mesenchymal stem cells into the renal medulla attenuated salt sensitive hypertension in Dahl S rat. AB - Adult stem cell deficiency has been implicated in the pathogenic mechanism for various diseases. Renal medullary dysfunction is one of the major mechanisms for the development of hypertension in Dahl salt-sensitive (S) rats. The present study first detected a stem cell deficiency in the renal medulla in Dahl S rats and then tested the hypothesis that transplantation of mesenchymal stem cells (MSCs) into the renal medulla improves salt-sensitive hypertension in Dahl S rats. Immunohistochemistry and flowcytometry analyses showed a significantly reduced number of stem cell marker CD133+ cells in the renal medulla from Dahl S rats compared with controls, suggesting a stem cell deficiency. Rat MSCs or control cells were transplanted into the renal medulla in uninephrectomized Dahl S rats, which were then treated with a low- or high-salt diet for 20 days. High salt-induced sodium retention and hypertension was significantly attenuated in MSC-treated rats compared with control cell-treated rats. Meanwhile, high-salt induced increases of proinflammatory factors, monocyte chemoattractant protein-1, and interleukin-1beta, in the renal medulla were blocked by MSC treatment. Furthermore, immunostaining showed that high-salt-induced immune cell infiltration into the renal medulla was substantially inhibited by MSC treatment. These results suggested that stem cell defect in the renal medulla may contribute to the hypertension in Dahl S rats and that correction of this stem cell defect by MSCs attenuated hypertension in Dahl S rats through anti-inflammation. KEY MESSAGE: Stem cell defect in the renal medulla may contribute to salt-sensitive hypertension Stem cell therapy is a potential therapeutic strategy for salt sensitive hypertension Normal stem cell inhibits the inflammatory response to high salt in the renal medulla. PMID- 25131938 TI - Understanding key influencers' attitudes and beliefs about healthy public policy change for obesity prevention. AB - OBJECTIVE: As overweight and obesity is a risk factor for chronic diseases, the development of environmental and healthy public policy interventions across multiple sectors has been identified as a key strategy to address this issue. METHODS: In 2009, a survey was developed to assess the attitudes and beliefs regarding health promotion principles, and the priority and acceptability of policy actions to prevent obesity and chronic diseases, among key policy influencers in Alberta and Manitoba, Canada. Surveys were mailed to 1,765 key influencers from five settings: provincial government, municipal government, school boards, print media companies, and workplaces with greater than 500 employees. A total of 236 surveys were completed with a response rate of 15.0%. RESULTS: Findings indicate nearly unanimous influencer support for individual focused policy approaches and high support for some environmental policies. Restrictive environmental and economic policies received weakest support. Obesity was comparable to smoking with respect to perceptions as a societal responsibility versus a personal responsibility, boding well for the potential of environmental policy interventions for obesity prevention. CONCLUSIONS: This level of influencer support provides a platform for more evidence to be brokered to policy influencers about the effectiveness of environmental policy approaches to obesity prevention. PMID- 25131940 TI - DFT investigation of the mechanism of E/Z isomerization of nitrones. AB - The hitherto unknown mechanism of E/Z isomerization of nitrones, with important implications in 1,3-dipolar cycloaddition chemistry, has been investigated using density functional theory calculations. Unimolecular and bimolecular processes have also been considered. Both concerted and stepwise mechanisms involving either zwitterionic or diradical species have been studied. The unimolecular torsional mechanism and isomerization through intermediate oxaziridines present energy barriers too high to justify the observed experimental results. Several bimolecular processes involving an initial dimerization are possible. Among them, the concerted process can be discarded in terms of energy barrier. Zwitterionic intermediates are too high in energy to be considered. From the two possible diradical approaches consisting of either C-O or C-C coupling, the latter is the most favored. Thus, the mechanism of E/Z isomerization of nitrones proceeds via a diradical bimolecular process involving an initial dimerization through a C-C coupling followed by a dedimerization, with energy barriers for the rate-limiting step of 29.9 kcal/mol for C-methyl nitrones and 25.8 kcal/mol for C (methoxycarbonyl) nitrones. These values are in very good agreement with the experimental data previously measured through kinetic experiments. PMID- 25131939 TI - The implementation of a protocol promoting the safe practice of brain death determination. AB - PURPOSE: The purpose of the study is to describe the implementation of measures introduced in Israel in 2009 to promote the safe practice of brain death determination (BDD). MATERIALS AND METHODS: The measures require (1) physicians to undergo a mandatory training course, (2) the mandatory performance of an ancillary test, and (3) retrospective examination of all BDD forms by an independent committee. Any deviations from practice parameters were noted. Surveys were also undertaken to assess (i) the attitude of local physicians to the measures and (ii) whether similar measures are in place in Europe and whether they were considered necessary. RESULTS: After implementation, the measures resulted in the absence of deviations from practice parameters over time. A majority of local physician (n = 64) felt the measures added a sense of security to BDD (73%) and ensured its proper performance (85%). The European survey (n = 20 countries) revealed (1) specialized BDD training is required in 60%, provided in 50%, while felt necessary by 80%; (2) independent supervision of BDD is performed in only one other country; and (3) BDD is performed country-wide using the same criteria in 80% while felt necessary by 95%. CONCLUSION: The measures were successfully implemented, reduced diversity in patient testing, and positively accepted by local physicians. Wider application of the measures may be appropriate as suggested by the results of a European survey and the variability of BDD reported in the literature. PMID- 25131941 TI - High prevalence of early hypothalamic-pituitary damage in childhood brain tumor survivors: need for standardized follow-up programs. AB - INTRODUCTION: Childhood brain tumor survivors (CBTS) are at increased risk to develop endocrine disorders. Alerted by two cases who experienced delay in diagnosis of endocrine deficiencies within the first 5 years after brain tumor diagnosis, our aim was to investigate the current screening strategy and the prevalence of endocrine disorders in survivors of a childhood brain tumor outside of the hypothalamic-pituitary region, within the first 5 years after diagnosis. PROCEDURES: Firstly, we performed a retrospective study of 47 CBTS treated in our center, diagnosed between 2008 and 2012. Secondly, the literature was reviewed for the prevalence of endocrine disorders in CBTS within the first 5 years after diagnosis. RESULTS: Of 47 CBTS eligible for evaluation, in 34% no endocrine parameters had been documented at all during follow up. In the other 66%, endocrine parameters had been inconsistently checked, with different parameters at different time intervals. In 19% of patients an endocrine disorder was found. At literature review 22 studies were identified. The most common reported endocrine disorder within the first 5 years after diagnosis was growth hormone deficiency (13-100%), followed by primary gonadal dysfunction (0-91%) central hypothyroidism (0-67%) and primary/subclinical hypothyroidism (range 0-64%). CONCLUSION: Endocrine disorders are frequently seen within the first 5 years after diagnosis of a childhood brain tumor outside of the hypothalamic-pituitary region. Inconsistent endocrine follow up leads to unnecessary delay in diagnosis and treatment. Endocrine care for this specific population should be improved and standardized. Therefore, high-quality studies and evidence based guidelines are warranted. PMID- 25131942 TI - Foetal exposure to maternal depression predicts cortisol responses in infants: findings from rural South India. AB - BACKGROUND: Maternal depression during pregnancy is associated with an increased risk of adverse child outcomes. One potential mechanism is the influence of antenatal depression on the foetal hypothalamic-pituitary-adrenal axis. This can be observed as disturbances in baseline cortisol secretion during childhood. The influence of antenatal depression on infant cortisol reactivity to a stressor may provide further insight into this association. In addition, the dose-response relationship between foetal exposure to antenatal depression and infant cortisol reactivity is unclear. METHODS: A consecutive sample of 133 pregnant women in their third trimester was recruited from an antenatal clinic in Karnataka, South India. Women were assessed for depression before and after birth on the Edinburgh Postnatal Depression Scale (EPDS) and the Kessler 10 Scale. Salivary cortisol response to immunization was measured in 58 infants at 2 months of age. We aimed (i) to investigate the association between antenatal depression and infant cortisol reactivity to immunization and (ii) to explore whether the relationship is dose-dependent. RESULTS: Exposure to antenatal depression independently predicted elevated infant cortisol responses to immunization (beta = 0.53, P = 0.04). The association was found to be U-shaped, for antenatal depression measured on the EPDS, with the infants exposed to the highest and lowest levels of maternal antenatal EPDS scores during intra-uterine life showing elevated cortisol responses to immunization (R(2) = 0.20, P = 0.02). Infants exposed to moderate levels of maternal antenatal depression showed the lowest cortisol response to immunization. CONCLUSIONS: These findings suggest that the association between antenatal depression and infant cortisol reactivity is dose dependent and U-shaped, implying that infants exposed to both low and high levels of maternal depression showed greater reactivity. The study provides the first evidence of such an association from a low-income setting. PMID- 25131944 TI - Clinical Neuropathology image 5-2014: alpha-synuclein pathology in the ependyma in Parkinson's disease. PMID- 25131945 TI - Detection of disease-associated alpha-synuclein in the cerebrospinal fluid: a feasibility study. AB - With the aim to evaluate the significance and reliability of detecting disease specific alpha-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA and bead-assay. We used a commercial antibody (5G4) that does not bind to the physiological monomeric form of alpha-synuclein, but is highly specific for the disease-associated forms, including high molecular weight fraction of beta-sheet rich oligomers. We applied both tests in CSF from a series of neuropathologically confirmed alpha-synucleinopathy cases, including Parkinson' disease dementia (PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer' disease (n = 6), and control patients without neurodegenerative pathologies (n = 9). Disease-specific alpha-synuclein was detectable in the CSF in a subset of patients with alpha-synuclein pathology in the brain. When combined with the analysis of total alpha-synuclein, the bead-assay for disease-specific alpha synuclein was highly specific for PDD/DLB. Detection of disease-associated alphasynuclein combined with the total levels of alpha-synuclein is a promising tool for the in-vivo diagnosis of alpha-synucleinopathies, including PDD and LBD. PMID- 25131946 TI - Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention. AB - Ethanol is the most common human teratogen, and its consumption during pregnancy can produce a wide range of abnormalities in infants known as fetal alcohol spectrum disorder (FASD). The major characteristics of FASD can be divided into: (i) growth retardation, (ii) craniofacial abnormalities, and (iii) central nervous system (CNS) dysfunction. FASD is the most common cause of nongenetic mental retardation in Western countries. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, the induction of oxidative stress is believed to be one central process linked to the development of the disease. Currently, there is no known effective strategy for prevention (other than alcohol avoidance) or treatment. In the present review we will provide the state of art in the evidence for the use of antioxidants as a potential therapeutic strategy for the treatment using whole-embryo and culture cells models of FASD. We conclude that the imbalance of the intracellular redox state contributes to the pathogenesis observed in FASD models, and we suggest that antioxidant therapy can be considered a new efficient strategy to mitigate the effects of prenatal ethanol exposure. PMID- 25131947 TI - Different HBsAg decline after 3 years of therapy with entecavir in patients affected by chronic hepatitis B HBeAg-negative and genotype A, D and E. AB - The role of measurement of hepatitis B "s" antigen (HBsAg) during the therapy with oral nucleos(t)ide analogues is still debatable. The HBsAg declines after 3 years of therapy with entecavir (ETV) was investigated among patients affected by hepatitis B virus (HBV), e antigen (HBeAg)-negative and genotypes A, D and E. A prospective cohort of 123 patients was enrolled consecutively from April 2007 to May 2010 with at least 3 years of treatment with ETV. Patients with chronic HBV infection, HBeAg-negative, naive for previous treatment and with virological response to ETV were included in the study. HBsAg level and HBV-DNA were tested every 3 months during the first year of treatment, then every 6 months for a time of at least 3 years. After 3 years, HBsAg decline was 0.77 log IU/ml, 0.65 log IU/ml, 0.45 respectively; A versus D (P = 0.012), A versus E (P < 0.001), D versus E (P < 0.001). In the multivariate linear regression analysis only the HBV genotype was predictive of HBsAg decline after 3 years of treatment (P < 0.001). The expected time to HBsAg loss was 15.6 years for the A genotype, 17 years for D, 24.6 years for E (P < 0.001). The treatment with ETV leads the different kinetics in HBsAg decline among genotypes A, D and E; the expected time of HBsAg loss was significantly higher in E genotype compared to A and D genotype. PMID- 25131948 TI - Transcript elongation factors: shaping transcriptomes after transcript initiation. AB - Elongation is a dynamic and highly regulated step of eukaryotic gene transcription. A variety of transcript elongation factors (TEFs), including modulators of RNA polymerase II (RNAPII) activity, histone chaperones, and histone modifiers, have been characterized from plants. These factors control the efficiency of transcript elongation of subsets of genes in the chromatin context and thus contribute to tuning gene expression programs. We review here how genetic and biochemical analyses, primarily in Arabidopsis thaliana, have advanced our understanding of how TEFs adjust plant gene transcription. These studies have revealed that TEFs regulate plant growth and development by modulating diverse processes including hormone signaling, circadian clock, pathogen defense, responses to light, and developmental transitions. PMID- 25131949 TI - Imatinib mesylate plus hydroxyurea chemotherapy for cerebellar meningioma in a Belgian Malinois dog. AB - An 8-year-old intact male Belgian Malinois, weighing 37.2 kg, was referred for evaluation due to right side facial paresis, ataxia and a 2-month history of decreased cognitive ability. Physical and neurological examinations revealed mild depression, left-sided head tilt, right-sided facial paresis and ataxia. A well demarcated, broad-based cerebellar mass and hyperostosis were found on CT imaging of the brain. Based on these CT findings, a cerebellar meningioma was strongly suspected. Hydroxyurea and prednisolone were administered; after 4 weeks, there was reduction in mass size as compared to initial CT results. However, the mass size was found to have grown 6 weeks after hydroxyurea treatment. We then prescribed a combination of imatinib mesylate and hydroxyurea. Two weeks following combination treatment, the mass size had reduced significantly. The mass continuously decreased in size until the patient died during anesthesia. Cerebellar transitional meningioma was confirmed by histopathologic examination. To the author's knowledge, this is the first reported case of imatinib mesylate plus hydroxyurea therapy for the treatment of meningioma in veterinary medicine. PMID- 25131950 TI - Profiling of serum metabolites in canine lymphoma using gas chromatography mass spectrometry. AB - Canine lymphoma is a common cancer that has high rates of complete remission with combination chemotherapy. However, the duration of remission varies based on multiple factors, and there is a need to develop a method for early detection of recurrence. In this study, we compared the metabolites profiles in serum from 21 dogs with lymphoma and 13 healthy dogs using gas chromatography mass spectrometry (GC-MS). The lymphoma group was separated from the control group in an orthogonal projection to latent structure with discriminant analysis (OPLS-DA) plot using ions of m/z 100-600, indicating that the metabolites profiles in lymphoma cases differed from those in healthy dogs. The lymphoma group was also separated from the control group on OPLS-DA plot using 29 metabolites identified in all serum samples. Significant differences were found for 16 of these metabolites with higher levels in the lymphoma group for 15 of the metabolites and lower levels for inositol. An OPLS-DA plot showed separation of the lymphoma and healthy groups using these 16 metabolites only. These results indicate that metabolites profile with GC-MS may be a useful tool for detection of potential biomarker and diagnosis of canine lymphoma. PMID- 25131951 TI - Internet searches and allergy: temporal variation in regional pollen counts correlates with Google searches for pollen allergy related terms. PMID- 25131952 TI - Are the fabellae bisected by the femoral cortices in a true craniocaudal pelvic limb radiograph? AB - OBJECTIVES: To assess whether the bisection of the fabellae by their respective femoral cortices is a useful criterion for assessing positioning of craniocaudal pelvic limb radiographs, and whether this is consistent in limbs affected or unaffected by medial patella luxation. METHODS: Computed tomography multi-planar reconstructions were used to determine the relative positions of the fabellae with respect to the femoral cortices. RESULTS: Only 36% of fabellae overall were bisected by the femoral cortex. There was no significant difference between limbs affected or unaffected by medial patella luxation. CLINICAL SIGNIFICANCE: The accurate measurement of femoral varus angle is important in pre-surgical planning of distal femoral ostectomy. Radiography is normally used to obtain the femoral varus angle, and femoral rotational malpositioning will induce errors in the femoral varus angle measured. Bisection of the fabellae by the femoral cortices is commonly cited as a criterion by which to assess whether a radiographic projection is truly craniocaudal, yet this study has shown this not to be valid. PMID- 25131954 TI - Reduction of the scanning time by total variation minimization reconstruction for X-ray tomography in a SEM. AB - Total variation minimization is applied to the particular case of X-ray tomography in a scanning electron microscope. To prove the efficiency of this reconstruction method, noise-free and noisy data based on the Shepp & Logan phantom have been simulated. These simulations confirm that Total variation minimization-reconstruction algorithm better manages data containing low number of projections with respect to simultaneous iterative reconstruction technique or filtered backprojection, even in the presence of noise. The algorithm has been applied to real data sets, with a low angular sampling and a high level of noise. Two samples containing micro-interconnections have been analyzed and 3D reconstructions show that Total variation minimization-based algorithm performs well even with 60 projections in order to properly recover a 500 nm diameter void inside a copper interconnection. PMID- 25131953 TI - Conformational and aggregation properties of the 1-93 fragment of apolipoprotein A-I. AB - Several disease-linked mutations of apolipoprotein A-I, the major protein in high density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often contain N-terminal fragments of the protein. Here, we present a combined computational and experimental study of the fibril-associated disordered 1-93 fragment of this protein, in wild-type and mutated (G26R, S36A, K40L, W50R) forms. In atomic-level Monte Carlo simulations of the free monomer, validated by circular dichroism spectroscopy, we observe changes in the position-dependent beta-strand probability induced by mutations. We find that these conformational shifts match well with the effects of these mutations in thioflavin T fluorescence and transmission electron microscopy experiments. Together, our results point to molecular mechanisms that may have a key role in disease-linked aggregation of apolipoprotein A-I. PMID- 25131955 TI - Antimicrobial susceptibility and molecular characterization of Mycobacterium intracellulare in China. AB - Mycobacterium avium complex (MAC) is the most common non-tuberculosis mycobacterial pathogen isolated from respiratory samples, mainly including two species, Mycobacterium avium (M. avium) and Mycobacterium intracellulare (M. intracellulare). Although these two species belong to the same group, M. avium and M. intracellulare reveal significantly differences in pathogenicity and biology. Nevertheless, little is known regarding the drug resistant details profile of M. avium or M. intracellulare instead of MAC. Here, we examined the antimicrobial susceptibility profiles of 52 clinical M. intracellulare isolates against fourteen antimicrobial agents, which are widely selected for the treatment of nontuberculous mycobacteria (NTM) infection. The drug susceptibility test revealed that clarithromycin (47/52, 90.4%), rifampicin (41/52, 78.8%) and capreomycin (40/52, 76.9%) revealed highly antimicrobial activities against M. intracellulare isolates in vitro. Furthermore, all clarithromycin resistant isolates harbored mutations in the 23S rRNA gene, and the percentage of amikacin resistant ones with mutation in the rrs gene is 62.5% (10/16). The Hunter-Gaston Discriminatory Index (HGDI) value for the 16-loci Variable Number of Tandem Repeat (VNTR) typing of M. intracellulare isolates was 0.994, and M. intracellulare resistance to moxifloxacin was significantly more commonly found in clustered strains than in nonclustered strains (chi(2)=5.551, P=0.040). In conclusion, our data demonstrated that clarithromycin and capreomycin revealed highly antimicrobial activities against M. intracellulare isolates, and clarithromycin and amikacin resistance could be detected more readily and rapidly using molecular scanning of corresponding drug target than conventional drug susceptibility testing. We also found that infection by clustered strains was significantly associated with resistance to moxifloxacin. PMID- 25131956 TI - Synthesis and biological evaluation of podophyllotoxin congeners as tubulin polymerization inhibitors. AB - A series of new podophyllotoxin derivatives containing structural modifications at C-7, C-8, and C-9 were synthesized and evaluated for their cytotoxic activity against three human cancer cell lines. All the synthesized compounds showed significant growth inhibition with GI50 values in micromolar levels while some of the compounds were several times more potent against MCF-7 and HeLa cell lines than MIAPACA cell line. Three compounds (12a, 12d and 12e) emerged as potent compounds with broad spectrum of cytotoxic activity against all the tested cell lines with GI50 values in the range of 0.01-2.1 MUM. These compounds induce microtubule depolymerization and arrests cells at the G2/M phase of the cell cycle. Moreover, compounds 12d and 12e disrupted microtubule network and accumulated tubulin in the soluble fraction in a similar manner to their parent podophyllotoxin scaffold. In addition, structure activity relationship studies within the series were also discussed. Molecular docking studies of these compounds into the colchicine-binding site of tubulin, revealed possible mode of inhibition by these compounds. PMID- 25131957 TI - Development of novel membrane active lipidated peptidomimetics active against drug resistant clinical isolates. AB - A new series of small cationic lipidated peptidomimetics have been synthesized and found to be highly active against several susceptible as well as drug resistant clinical isolates of bacteria and fungi. All lipidated peptidomimetics do not cause significant lysis of human erythrocytes (HC50>200MUg/mL). Calcein dye leakage experiment revealed membranolytic effect of LPEP08 which was further confirmed by scanning electron microscopy (SEM). The involvement of intracellular targets as an alternate mode of action was precluded by DNA retardation assay. Additionally, LPEP08 exhibit high proteolytic stability and dose not elicit resistance against drug resistant clinical isolate of Staphylococcusaureus, even after 16 rounds of passaging. These results demonstrate the potential of lipidated peptidomimetics as biocompatible anti-infective therapeutics. PMID- 25131959 TI - Natural, engineered, and artificial biocatalysts for organic synthesis. PMID- 25131958 TI - Ethyl 2-(benzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6 carboxylate analogues as a new scaffold for protein kinase casein kinase 2 inhibitor. AB - Protein kinase casein kinase 2 (PKCK2) is a constitutively active, growth factor independent serine/threonine kinase, and changes in PKCK2 expression or its activity are reported in many cancer cells. To develop a novel PKCK2 inhibitor(s), we first performed cell-based phenotypic screening using 4000 chemicals purchased from ChemDiv chemical libraries (2000: randomly selected; 2000: kinase-biased) and performed in vitro kinase assay-based screening using hits found from the first screening. We identified compound 24 (C24)[(Z)-ethyl 5 (4-chlorophenyl)-2-(3,4-dihydroxybenzylidene)-7-methyl-3-oxo-3,5-dihydro-2H thiazolo[3,2-a] pyrimidine-6-carboxylate] as a novel inhibitor of PKCK2 that is more potent and selective than 4,5,6,7-tetrabromobenzotriazole (TBB). In particular, compound 24 [half maximal inhibitory concentration (IC50)=0.56MUM] inhibited PKCK2 2.2-fold more efficiently than did TBB (IC50=1.24MUM), which is quite specific toward PKCK2 with respect to ATP binding, in a panel of 31 human protein kinases. The Ki values of compound 24 and TBB for PKCK2 were 0.78MUM and 2.70MUM, respectively. Treatment of cells with compound 24 inhibited endogenous PKCK2 activity and showed anti-proliferative and pro-apoptotic effects against stomach and hepatocellular cancer cell lines more efficiently than did TBB. As expected, compound 24 also enabled tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-resistant cancer cells to be sensitive toward TRAIL. In comparing the molecular docking of compound 24 bound to PKCK2alpha versus previously reported complexes of PKCK2 with other inhibitors, our findings suggest a new scaffold for specific PKCK2alpha inhibitors. Thus, compound 24 appears to be a selective, cell-permeable, potent, and novel PKCK2 inhibitor worthy of further characterization. PMID- 25131960 TI - The Nurse-Based Age Independent Intervention to Limit Evolution of Disease After Acute Coronary Syndrome (NAILED ACS) Risk Factor Trial: Protocol for a Randomized Controlled Trial. AB - BACKGROUND: Secondary prevention after acute coronary syndrome (ACS) is essential to reduce morbidity and mortality, but related studies have been fairly small or performed as clinical trials with non-representative patient selection. Long-term follow-up data are also minimal. A nurse-led follow-up for risk factor improvement may be effective, but the evidence is limited. OBJECTIVE: The aims of this study are to perform an adequately sized, nurse-led, long-term secondary preventive follow-up with inclusion of an unselected population of ACS patients. The focus will be on lipid and blood pressure control as well as tobacco use and physical activity. METHODS: The study will consist of a randomized, controlled, long-term, population-based trial with two parallel groups. Patients will be included during the initial hospital stay. Important outcome variables are total cholesterol, low-density lipoprotein (LDL) cholesterol, and sitting systolic and diastolic blood pressure. Outcomes will be measured after 12, 24, and 36 months of follow-up. Trained nurses will manage the intervention group with the aim of achieving set treatment goals as soon as possible. The control group will receive usual care. At least 250 patients will be included in each group to reliably detect a difference in mean LDL of 0.5 mmol/L and in mean systolic blood pressure of 5 mmHg. RESULTS: The study is ongoing and recruitment of participants will continue until December 31, 2014. CONCLUSIONS: This study will test the hypothesis that a nurse-led, long-term follow-up after an ACS with a focus on achieving treatment goals as soon as possible is an effective secondary preventive method. If proven effective, this method could be implemented in general practice at a low cost. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 96595458; http://www.controlled trials.com/ISRCTN96595458 (Archived by WebCite at http://www.webcitation.org/6RlyhYTYK). PMID- 25131962 TI - Application of isothermal titration calorimetry for characterizing thermodynamic parameters of biomolecular interactions: peptide self-assembly and protein adsorption case studies. AB - The complex nature of macromolecular interactions usually makes it very hard to identify the molecular-level mechanisms that ultimately dictate the result of these interactions. This is especially evident in the case of biological systems, where the complex interaction of molecules in various situations may be responsible for driving biomolecular interactions themselves but also has a broader effect at the cell and/or tissue level. This review will endeavor to further the understanding of biomolecular interactions utilizing the isothermal titration calorimetry (ITC) technique for thermodynamic characterization of two extremely important biomaterial systems, viz., peptide self-assembly and nonfouling polymer-modified surfaces. The advantages and shortcomings of this technique will be presented along with a thorough review of the recent application of ITC to these two areas. Furthermore, the controversies associated with the enthalpy-entropy compensation effect as well as thermodynamic equilibrium state for such interactions will be discussed. PMID- 25131964 TI - Quantifying the social impact of research and medical journals. PMID- 25131961 TI - Translation of clinical trial outcomes to metastatic colorectal cancer patients in community practice. AB - AIM: As multiple new agents have been added to the treatment options for patients with metastatic colorectal cancer, survival outcomes in clinical trials have continued to improve. Similarly, improved outcomes in routine clinical care would be anticipated, but have yet to be demonstrated. Here, we aim to explore whether survival gains demonstrated in clinical trials are reproducible in routine practice, and whether factors beyond new therapies may be contributing to improved outcomes. METHODS: Comparison of comprehensive treatment and outcome data for consecutive patients diagnosed in 2003-2006 versus 2007-2010 at four specialist hospitals in Australia. RESULTS: Data were available on 965 patients; median age 66.1 years (range 19-93), 572 (59%) were male. For the latter time period, there was an increase in patients receiving any treatment (74% vs 66%, P = 0.014), initial combination chemotherapy (57% vs 44%, P < 0.001) and bevacizumab (15% vs 2%, P < 0.001). There was no change in the percentage undergoing resection of distant metastatic disease. For the latter time period, overall survival was improved (median 24.8 vs 17.4 months, P < 0.001), including patients not receiving any active treatment (11.9 vs 6.4 months, P = 0.014). CONCLUSION: Survival outcomes in routine clinical care for patients with metastatic colorectal cancer have markedly improved in recent years following the introduction of multiple new active therapies. The improved outcome of untreated patients suggests earlier diagnosis and improved supportive care may also be contributing to survival gains. PMID- 25131963 TI - Multi-modality management for loco-regionally advanced laryngeal and hypopharyngeal cancer: balancing the benefit of efficacy and functional preservation. AB - The 5-year overall survival (OS) of loco-regionally advanced laryngeal and hypopharyngeal carcinoma (LA-LHC) has declined over the past two decades following the wide application of non-surgical approaches. We aimed to define the new role of open surgery combined with adjuvant chemoradiotherapy in the treatment of LA-LHC for improving survival while maintaining a functional larynx. In the current study, 90 LA-LHC patients treated with open surgery followed by postoperative RT/CRT in our institute from May 2005 to December 2012 were retrospectively analyzed. OS, disease-free survival (DFS), loco-regional failure free survival (LRFFS) and distant metastasis-free survival (DMFS) were calculated, and prognostic factors were analyzed. Functional larynx preservation results were evaluated according to the head and neck quality of life (QoL) Scale. With a median follow-up period of 37 months, the 3- and 5-year OS, DFS, LRFFS and DMFS were 71.3, 63.7, 85.9, 73.7 and 55.9, 53.0, 81.6, 71.9 %, respectively. Vascular embolism and extracapsular extension (ECE) of the lymph nodes were prognostic factors for poorer OS (p = 0.045 and 0.046, respectively). Vascular embolism was the only prognostic factor for poorer DMFS (p = 0.005). Patients who underwent a conservative partial laryngectomy (CPL) experienced a higher QoL in the domains of speech, swallowing and emotion. Functional larynx preservation was achieved in 36/45 patients (80 %) who received CPL. The results of our study demonstrated that CPL followed by adequate adjuvant therapy could achieve superior oncological results compared with non-surgical approaches in LA LHC patients while also maintaining satisfactory functional larynx in a majority of patients. PMID- 25131965 TI - Prescribing antibiotics: a battle of resistance. PMID- 25131966 TI - Priorities for people with disabilities in New Zealand. PMID- 25131967 TI - Under-use of the Ross operation--a lost opportunity. PMID- 25131968 TI - Telemonitoring implants for patients with heart failure. PMID- 25131969 TI - Risk and decision making in patients with hypertension. PMID- 25131970 TI - Heparin monotherapy for percutaneous coronary intervention? PMID- 25131971 TI - Dyslipidaemia in perspective. PMID- 25131973 TI - Adhesion barriers for abdominal surgery and oncology. PMID- 25131974 TI - Adhesion barriers for abdominal surgery and oncology - Authors' reply. PMID- 25131975 TI - Better treatment of XDR tuberculosis needed in South Africa. PMID- 25131976 TI - Better treatment of XDR tuberculosis needed in South Africa - Author's reply. PMID- 25131977 TI - Implant-based multiparameter telemonitoring of patients with heart failure (IN TIME): a randomised controlled trial. AB - BACKGROUND: An increasing number of patients with heart failure receive implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation defibrillators (CRT-Ds) with telemonitoring function. Early detection of worsening heart failure, or upstream factors predisposing to worsening heart failure, by implant-based telemonitoring might enable pre-emptive intervention and improve outcomes, but the evidence is weak. We investigated this possibility in IN-TIME, a clinical trial. METHODS: We did this randomised, controlled trial at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel. We enrolled patients with chronic heart failure, NYHA class II-III symptoms, ejection fraction of no more than 35%, optimal drug treatment, no permanent atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a 1 month run-in phase, patients were randomly assigned (1:1) to either automatic, daily, implant-based, multiparameter telemonitoring in addition to standard care or standard care without telemonitoring. Investigators were not masked to treatment allocation. Patients were masked to allocation unless they were contacted because of telemonitoring findings. Follow-up was 1 year. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for heart failure, change in NYHA class, and change in patient global self-assessment, for the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00538356. FINDINGS: We enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring, 331 to control). Mean age was 65.5 years and mean ejection fraction was 26%. 285 (43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III. Most patients received CRT-Ds (390; 58.7%). At 1 year, 63 (18.9%) of 333 patients in the telemonitoring group versus 90 (27.2%) of 331 in the control group (p=0.013) had worsened composite score (odds ratio 0.63, 95% CI 0.43-0.90). Ten versus 27 patients died during follow-up. INTERPRETATION: Automatic, daily, implant-based, multiparameter telemonitoring can significantly improve clinical outcomes for patients with heart failure. Such telemonitoring is feasible and should be used in clinical practice. FUNDING: Biotronik SE & Co. KG. PMID- 25131978 TI - Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. AB - BACKGROUND: We aimed to investigate whether the benefits of blood pressure lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform treatment decisions for blood pressure-lowering therapy, as is recommended for lipid-lowering therapy. METHODS: This meta-analysis included individual participant data from trials that randomly assigned patients to either blood pressure-lowering drugs or placebo, or to more intensive or less intensive blood pressure-lowering regimens. The primary outcome was total major cardiovascular events, consisting of stroke, heart attack, heart failure, or cardiovascular death. Participants were separated into four categories of baseline 5-year major cardiovascular risk using a risk prediction equation developed from the placebo groups of the included trials (<11%, 11-15%, 15-21%, >21%). FINDINGS: 11 trials and 26 randomised groups met the inclusion criteria, and included 67,475 individuals, of whom 51,917 had available data for the calculation of the risk equations. 4167 (8%) had a cardiovascular event during a median of 4.0 years (IQR 3.4-4.4) of follow-up. The mean estimated baseline levels of 5-year cardiovascular risk for each of the four risk groups were 6.0% (SD 2.0), 12.1% (1.5), 17.7% (1.7), and 26.8% (5.4). In each consecutive higher risk group, blood pressure-lowering treatment reduced the risk of cardiovascular events relatively by 18% (95% CI 7-27), 15% (4-25), 13% (2-22), and 15% (5-24), respectively (p=0.30 for trend). However, in absolute terms, treating 1000 patients in each group with blood pressure-lowering treatment for 5 years would prevent 14 (95% CI 8-21), 20 (8-31), 24 (8-40), and 38 (16-61) cardiovascular events, respectively (p=0.04 for trend). INTERPRETATION: Lowering blood pressure provides similar relative protection at all levels of baseline cardiovascular risk, but progressively greater absolute risk reductions as baseline risk increases. These results support the use of predicted baseline cardiovascular disease risk equations to inform blood pressure-lowering treatment decisions. FUNDING: None. PMID- 25131979 TI - Bivalirudin versus heparin in patients planned for percutaneous coronary intervention: a meta-analysis of randomised controlled trials. AB - BACKGROUND: Bivalirudin is an alternative to heparin in patients undergoing percutaneous coronary intervention (PCI). We aimed to define the effects of a bivalirudin-based anticoagulation regimen compared with a heparin-based anticoagulation regimen on ischaemic and bleeding outcomes. METHODS: We searched Medline, the Cochrane Library, and relevant meeting abstracts (search done on April 9, 2014) for randomised trials that assessed bivalirudin versus heparin in patients planned for PCI. The primary efficacy endpoint was the incidence of major adverse cardiac events (MACE) up to 30 days. Secondary efficacy endpoints were death, myocardial infarction, ischaemia-driven revascularisation, and stent thrombosis. The primary safety endpoint was major bleeding up to 30 days. We calculated pooled risk ratios and 95% CIs using random-effects models. FINDINGS: We included data from 16 trials involving 33 958 patients, of whom 2422 experienced MACE and 1406 had a major bleed. There was an increase in the risk of MACE with bivalirudin-based regimens compared with heparin-based regimens (risk ratio 1.09, 95% CI 1.01-1.17; p=0.0204), which was largely driven by increases in myocardial infarction (1.12, 1.03-1.23) and seemingly also by ischaemia-driven revascularisation (1.16, 0.997-1.34) with bivalirudin compared with heparin, with no effect on mortality (0.99, 0.82-1.18). Bivalirudin increased the risk of stent thrombosis (risk ratio 1.38, 95% CI 1.09-1.74; p=0.0074), which was primarily due to an increase in acute cases in ST-segment elevation myocardial infarction (4.27, 2.28-8.00; p<0.0001). Overall, bivalirudin-based regimens lowered the risk of major bleeding (risk ratio 0.62, 95% CI 0.49-0.78; p<0.0001), but the magnitude of this effect varied greatly (p<0.0001) depending on whether glycoprotein IIb/IIIa inhibitors were used predominantly in the heparin arm only (0.53, 0.47-0.61; p<0.0001), provisionally in both arms (0.78, 0.51-1.19; p=0.25), or planned in both arms (1.07, 0.87-1.31; p=0.53). INTERPRETATION: Compared with a heparin-based regimen, a bivalirudin-based regimen increases the risk of myocardial infarction and stent thrombosis, but decreases the risk of bleeding, with the magnitude of the reduction depending on concomitant glycoprotein IIb/IIIa inhibitor use. Physicians should weigh the trade-off between ischaemic and bleeding events when choosing between different anticoagulant regimens. FUNDING: None. PMID- 25131980 TI - LDL cholesterol: controversies and future therapeutic directions. AB - Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60,000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications. PMID- 25131981 TI - HDL and cardiovascular disease. AB - The cholesterol contained within HDL is inversely associated with risk of coronary heart disease and is a key component of predicting cardiovascular risk. However, despite its properties consistent with atheroprotection, the causal relation between HDL and atherosclerosis is uncertain. Human genetics and failed clinical trials have created scepticism about the HDL hypothesis. Nevertheless, drugs that raise HDL-C concentrations, cholesteryl ester transfer protein inhibitors, are in late-stage clinical development, and other approaches that promote HDL function, including reverse cholesterol transport, are in early-stage clinical development. The final chapters regarding the effect of HDL-targeted therapeutic interventions on coronary heart disease events remain to be written. PMID- 25131982 TI - Triglycerides and cardiovascular disease. AB - After the introduction of statins, clinical emphasis first focussed on LDL cholesterol-lowering, then on the potential for raising HDL cholesterol, with less focus on lowering triglycerides. However, the understanding from genetic studies and negative results from randomised trials that low HDL cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2-10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk of acute pancreatitis and possibly cardiovascular disease. Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride lowering drugs are being developed, and large-scale trials have been initiated that will hopefully provide conclusive evidence as to whether lowering triglycerides reduces the risk of cardiovascular disease. PMID- 25131983 TI - Acute retinal necrosis presenting as bilateral acute angle closure. PMID- 25131984 TI - Incidence, management, and prevention of right ventricular perforation by pacemaker and implantable cardioverter defibrillator leads. AB - BACKGROUND: Cardiac perforation of the right ventricle (RV) is a rare but potentially life-threatening complication of both pacemaker (PM) and implantable cardioverter defibrillator (ICD) implant. Appropriate management is still uncertain. We assessed the incidence of subacute (24 hours-1 month) or delayed (>1 month) cardiac perforation by RV lead and the results of percutaneous lead extraction. METHOD: The study population included all patients diagnosed with subacute or delayed RV-lead perforation during the period 2007-2013. The incidence of perforation according to device type and fixation mechanism was calculated. The outcome of the percutaneous approach, consisting of lead extraction by simple traction, was assessed. RESULTS: Cardiac perforation was diagnosed in 14 (eight females, mean age 71 [range 47-83] years) patients out of 3,815 who received an RV-lead implant (0.4%). The overall incidence of RV-lead perforation was similar between ICD (0.3%) and PM (0.4%) implants (P = 1.0) and between active (0.5%) and passive (0.3%) fixation leads (P = 0.3). All perforating leads were originally placed at the RV apex. Five patients were asymptomatic, but all presented altered lead electrical parameters. Surgical removal of the lead was performed in one patient while in the remaining the leads were successfully extracted by direct manual traction in the absence of any complications. In all patients, new active fixation leads were positioned in the RV septum and the follow-up (42 +/- 27 months) was uneventful. CONCLUSIONS: RV perforation is a rare complication of both PM and ICD implants, regardless of the lead fixation mechanism. In most patients, percutaneous lead extraction is a safe and effective management approach. PMID- 25131986 TI - Ebola in West Africa. PMID- 25131985 TI - Current use of metformin in addition to insulin in pediatric patients with type 1 diabetes mellitus: an analysis based on a large diabetes registry in Germany and Austria. AB - BACKGROUND: With increasing obesity in childhood and adolescence, weight gain, and insulin resistance become also more frequent in patients with type 1 diabetes mellitus (T1DM). Especially during puberty, insulin therapy often has to be intensified and higher insulin doses are necessary. Some studies point to a beneficial effect of metformin in addition to insulin in these patients. In order to describe current practice and possible benefits, we compared pediatric T1DM patients with insulin plus metformin (n = 525) to patients with insulin therapy only (n = 57 487) in a prospective multicenter analysis. METHODS: Auxological and treatment data from 58 012 patients aged <21 yr with T1DM in the German/Austrian Diabetes Patienten Verlaufsdokumentation (DPV) registry were analyzed by multivariable mixed regression modeling. RESULTS: Patients with additional metformin were older [median (interquartile range)]: [16.1 (14.1-17.6) vs. 15.2 (11.5-17.5) yr] with female preponderance (61.0 vs. 47.2%, p < 0.01). They had higher body mass index-standard deviation score (BMI-SDS) [+2.03 (+1.29 to +2.56) vs. +0.51 (-0.12 to +1.15); p < 0.01] and glycated hemoglobin (HbA1c) (9.0 vs. 8.6%, p < 0.01). Hypertension (43.7 vs. 24.8%) and dyslipidemia (58.4 vs. 40.6%) were significantly more prevalent. Adjusted insulin dose was significantly higher (0.98 vs. 0.93 IU/kg bodyweight). In a subgroup of 285 patients followed-up longitudinally (average treatment period 1.42 yr), addition of metformin resulted in a slight reduction of BMI-SDS [-0.01 (-2.01 to +1.40)], but did not improve HbA1c or insulin requirement. CONCLUSION: Additional metformin therapy in T1DM is primarily used in obese females. Additional therapy with metformin was associated with minor benefits. PMID- 25131987 TI - Seeing the forest, but not the trees: pertinent considerations for examining acute changes in pulse wave velocity in response to pharmaceutical interventions and exercise. PMID- 25131988 TI - Expression of perilipin 2 (PLIN2) in porcine oocytes during maturation. AB - Perilipins have been reported to limit the interaction of lipases with neutral lipids within the droplets, thereby regulating neutral lipid accumulation and utilization. This study aimed to identify the location and expression of PLIN1 and PLIN2 in porcine oocytes during maturation. Quantitative real-time polymerase chain reaction (qRT-PCR), immunostaining and Western blot methods were used to characterize the expression and distribution patterns of PLIN1 and PLIN2 in porcine oocytes. The results showed that PLIN1 was not detectable in porcine oocytes. PLIN2 and BODIPY 493/503-detected neutral lipid droplets appeared identical distribution patterns and extensive colocalization in both GV and MII porcine oocytes. PLIN2 protein expression was higher in GV oocytes than that in MII oocytes (p < 0.05), although PLIN2 mRNA expression was similar in both groups. These findings suggested that PLIN2 was a major lipid droplet-associated protein in porcine oocytes. PMID- 25131990 TI - Structure-guided reprogramming of human cGAS dinucleotide linkage specificity. AB - Cyclic dinucleotides (CDNs) play central roles in bacterial pathogenesis and innate immunity. The mammalian enzyme cGAS synthesizes a unique cyclic dinucleotide (cGAMP) containing a 2'-5' phosphodiester linkage essential for optimal immune stimulation, but the molecular basis for linkage specificity is unknown. Here, we show that the Vibrio cholerae pathogenicity factor DncV is a prokaryotic cGAS-like enzyme whose activity provides a mechanistic rationale for the unique ability of cGAS to produce 2'-5' cGAMP. Three high-resolution crystal structures show that DncV and human cGAS generate CDNs in sequential reactions that proceed in opposing directions. We explain 2' and 3' linkage specificity and test this model by reprogramming the human cGAS active site to produce 3'-5' cGAMP, leading to selective stimulation of alternative STING adaptor alleles in cells. These results demonstrate mechanistic homology between bacterial signaling and mammalian innate immunity and explain how active site configuration controls linkage chemistry for pathway-specific signaling. PMID- 25131989 TI - Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. AB - Latent reservoirs of HIV-1-infected cells are refractory to antiretroviral therapies (ART) and remain the major barrier to curing HIV-1. Because latently infected cells are long-lived, immunologically invisible, and may undergo homeostatic proliferation, a "shock and kill" approach has been proposed to eradicate this reservoir by combining ART with inducers of viral transcription. However, all attempts to alter the HIV-1 reservoir in vivo have failed to date. Using humanized mice, we show that broadly neutralizing antibodies (bNAbs) can interfere with establishment of a silent reservoir by Fc-FcR-mediated mechanisms. In established infection, bNAbs or bNAbs plus single inducers are ineffective in preventing viral rebound. However, bNAbs plus a combination of inducers that act by independent mechanisms synergize to decrease the reservoir as measured by viral rebound. Thus, combinations of inducers and bNAbs constitute a therapeutic strategy that impacts the establishment and maintenance of the HIV-1 reservoir in humanized mice. PMID- 25131992 TI - Surface characteristics and microbial adherence ability of modified polymethylmethacrylate by fluoridated glass fillers. AB - BACKGROUND: The current study objectives were to evaluate the influence of fluoridated glass fillers loading on the surface roughness, wettability, and adherence of candida and bacteria with and without saliva presence to a polymethylmethacrylate (PMMA) denture base material surface. METHODS: Four concentrations of fluoridated glass fillers were added to PMMA: 1%, 2.5%, 5% and 10% by weight pre-polymerization and 0% was the control. Discs of each concentration were fabricated (n = 5 for each variable). Surface roughness (Ra ) was measured using atomic force microscopy (AFM). Wettability was assessed by measuring the contact angle of a sessile drop of water. Specimens were incubated with Candida albicans, or Streptococcus mutans with and without saliva coating. Adherence was presented as a percentage of the colonized surface area, counted using an optical microscope at x100 magnification. RESULTS: The 10% group showed significantly greater roughness than the control and 1% groups; however, no significant differences in contact angle values were detected. The microbial adhesion was inversely proportional to the fluoridated glass fillers concentration where 10% concentration significantly decreased candidal and bacterial adhesion compared to others. Saliva coating significantly decreased microbial adhesion. CONCLUSIONS: It was concluded that fluoridated glass fillers could decrease microbial adhesion to acrylic denture base without adversely affecting surface properties. PMID- 25131993 TI - MLPA Application in Clinical Diagnosis of DMD/BMD in Shanghai. AB - BACKGROUND: Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessive disorders caused by mutation in dystrophin gene. We reported 3-year clinic experience from a single hospital in Shanghai using multiplex ligation dependent probe amplification (MLPA) assay to detect DMD mutations. METHODS: Four hundred and fifty-one males and 184 females, who were clinically diagnosed as DMD/BMD patients or carriers at our hospital's outpatient clinic, were collected and performed with MLPA to detect DMD gene mutations. RESULTS: Seventeen novel mutation points not reported in the Leiden Muscular Dystrophy pages were identified in this study. We found that the most frequent deletion spots ranged from exon45 to exon52, and exon2, exon19 were the two most frequently detected duplication spots. CONCLUSION: The results of our study confirmed MLPA as an efficient clinical method for detecting DMD gene mutations in DMD/BMD patients. Single exon mutation detected by MLPA should be verified by other methods, and we should emphasize that only precise clinical molecular diagnosis can lead to the feasibility of prenatal diagnosis. PMID- 25131994 TI - Selective CH functionalization of methane, ethane, and propane by a perfluoroarene iodine(III) complex. AB - Direct partial oxidation of methane, ethane, and propane to their respective trifluoroacetate esters is achieved by a homogeneous hypervalent iodine(III) complex in non-superacidic (trifluoroacetic acid) solvent. The reaction is highly selective for ester formation (>99%). In the case of ethane, greater than 0.5 M EtTFA can be achieved. Preliminary kinetic analysis and density functional calculations support a nonradical electrophilic CH activation and iodine alkyl functionalization mechanism. PMID- 25131991 TI - Expression of alpha-subunit of alpha-glucosidase II in adult mouse brain regions and selected organs. AB - alpha-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an important enzyme in the folding of nascent glycoproteins, is heterodimeric, consisting of alpha (GIIalpha) and beta (GIIbeta) subunits. The catalytic GIIalpha subunit, with the help of mannose 6-phosphate receptor homology domain of GIIbeta, sequentially hydrolyzes two alpha1-3-linked glucose residues in the second step of N-linked oligosaccharide-mediated protein folding. The soluble GIIalpha subunit is retained in the ER through its interaction with the HDEL containing GIIbeta subunit. N-glycosylation and correct protein folding are crucial for protein stability and trafficking and cell surface expression of several proteins in the brain. Alterations in N-glycosylation lead to abnormalities in neuronal migration and mental retardation, various neurodegenerative diseases, and invasion of malignant gliomas. Inhibitors of GII are used to inhibit cell proliferation and migration in a variety of different pathologies, such as viral infection, cancer, and diabetes. Despite the widespread use of GIIalpha inhibitory drugs and the role of GIIalpha in brain function, little is known about its expression in brain and other tissues. Here, we report generation of a highly specific chicken antibody to the GIIalpha subunit and its characterization by Western blotting and immunoprecipitation using cerebral cortical extracts. By using this antibody, we showed that the GIIalpha protein is highly expressed in testis, kidney, and lung, with the lowest amount in heart. GIIalpha polypeptide levels in whole brain were comparable to those in spleen. However, a higher expression of GIIalpha protein was detected in the cerebral cortex, reflecting its continuous requirement in correct folding of cell surface proteins. PMID- 25131995 TI - Bibliometric performance of Acta Physiologica. PMID- 25131998 TI - Nomenclature for factors of the HLA system, update May 2014. PMID- 25131997 TI - Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless mice. AB - Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin-6, and MMP-1 were significantly suppressed, and type I procollagen expression was stimulated in UVB-irradiated and GA-treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP-1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor-beta1. Our data indicate that GA is a potential candidate for the prevention of UVB induced premature skin aging. PMID- 25131996 TI - Synchronous multiscale neuroimaging environment for critically sampled physiological analysis of brain function: hepta-scan concept. AB - Functional connectivity of the resting-state networks of the brain is thought to be mediated by very-low-frequency fluctuations (VLFFs <0.1 Hz) in neuronal activity. However, vasomotor waves and cardiorespiratory pulsations influence indirect measures of brain function, such as the functional magnetic resonance imaging blood-oxygen-level-dependent (BOLD) signal. How strongly physiological oscillations correlate with spontaneous BOLD signals is not known, partially due to differences in the data-sampling rates of different methods. Recent ultrafast inverse imaging sequences, including magnetic resonance encephalography (MREG), enable critical sampling of these signals. In this study, we describe a multimodal concept, referred to as Hepta-scan, which incorporates synchronous MREG with scalp electroencephalography, near-infrared spectroscopy, noninvasive blood pressure, and anesthesia monitoring. Our preliminary results support the idea that, in the absence of aliased cardiorespiratory signals, VLFFs in the BOLD signal are affected by vasomotor and electrophysiological sources. Further, MREG signals showed a high correlation coefficient between the ventromedial default mode network (DMNvmpf) and electrophysiological signals, especially in the VLF range. Also, oxy- and deoxyhemoglobin and vasomotor waves were found to correlate with DMNvmpf. Intriguingly, usage of shorter time windows in these correlation measurements produced significantly (p<0.05) higher positive and negative correlation coefficients, suggesting temporal nonstationary behavior between the measurements. Focus on the VLF range strongly increased correlation strength. PMID- 25131999 TI - Chronological changes in the microstructure of bone during peri-implant healing: a microcomputed tomographic evaluation. AB - Our objectives were to examine the titanium-bone interfaces chronologically and to clarify the process of osseointegration using microcomputed tomography (microCT). The mandibular premolars of 3 dogs were extracted and 12 weeks later 2 Straumann dental implants were installed in each quadrant. The microstructural changes at the bone-implant interface at the first, fourth, and eighth weeks after installation were evaluated by microCT and a 3-dimensional image was constructed. The microstructural measurements at the bone-implant interface, including the trabecular number (Tb.N), bone volume fraction (BV/TV), structure model index (SMI), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and connectivity density (Conn.D), were measured. Experimental outcomes were analysed for correlations between time and microstructural variables of trabecular bone. Tb.N increased significantly during the eighth week compared with that during the first and fourth week (p=0.001, 0.002). BV/TV increased generally with time and there were significant differences (p=0.003) between each time group. While Tb.Sp decreased with time and changed significantly during the eighth week compared with that during the first week (p=0.021), differences in SMI, Tb.Th and Conn.D did not differ significantly according to time of implant. The significant increase in the Tb.N and BV/TV during the eighth week after insertion of implants indicates that the formation of new bone before the eighth week is the key to osseointegration. PMID- 25132000 TI - Keloids in Rubinstein-Taybi syndrome: a clinical study. AB - BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomalies intellectual disability syndrome. One of the complications is keloid formation. Keloids are proliferative fibrous growths resulting from excessive tissue response to skin trauma. OBJECTIVES: To describe the clinical characteristics of keloids in individuals with RSTS reported in the literature and in a cohort of personally evaluated individuals with RSTS. PATIENTS AND METHODS: We performed a literature search for descriptions of RSTS individuals with keloids. All known individuals with RSTS in the Netherlands filled out three dedicated questionnaires. All individuals with (possible) keloids were personally evaluated. A further series of individuals with RSTS from the U.K. was personally evaluated. RESULTS: Reliable data were available for 62 of the 83 Dutch individuals with RSTS and showed 15 individuals with RSTS (24%) to have keloids. The 15 Dutch and 12 U.K. individuals with RSTS with keloids demonstrated that most patients have multiple keloids (n > 1: 82%; n > 5: 30%). Mean age of onset is 11.9 years. The majority of keloids are located on the shoulders and chest. The mean length * width of the largest keloid was 7.1 * 2.8 cm, and the mean thickness was 0.7 cm. All affected individuals complained of itching. Generally, treatment results were disappointing. CONCLUSIONS: Keloids occur in 24% of individuals with RSTS, either spontaneously or after a minor trauma, usually starting in early puberty. Management schedules have disappointing results. RSTS is a Mendelian disorder with a known molecular basis, and offers excellent opportunities to study the pathogenesis of keloids in general and to search for possible treatments. PMID- 25132001 TI - Development of a highly-potent anti-angiogenic VEGF8-109 heterodimer by directed blocking of its VEGFR-2 binding site. AB - Angiogenesis is a hallmark of various pathological conditions and is controlled by a variety of angiogenic factors. Blockade of vascular endothelial growth factor (VEGF) as the most pivotal stimulator of angiogenesis offers a promising therapeutic approach for some diseases, typically cancer. In the present study, a heterodimeric antagonistic VEGF was precisely designed based on structural information of recently-crystallized VEGF/VEGF receptor-2 (VEGFR-2/fetal liver kinase 1/kinase domain region) complex. Directed blocking of kinase domain region occurs via substitution of a VEGF receptor binding site by two peptide segments in one pole, whereas the binding domain of the other pole of VEGF was intact. Candidate peptides for substitution were selected considering to some sequence and structural criteria. A reliable model of modified VEGF was built, refined using molecular dynamics simulation and docked with VEGFR-2. Docking analysis revealed that binding affinity of mutant VEGF was notably diminished, corroborating our design. Heterodimeric VEGF was expressed, refolded and highly purified by two-step affinity chromatography. Dimerization of this antagonist was confirmed using some analytical techniques. Spectroscopic studies assured us to obtain the heterodimeric form of VEGF. Some angiogenic in vitro assays such endothelial cell proliferation and tube formation indicated that this antagonist is not only strongly capable of inhibiting angiogenesis (half maximal inhibitory concentration of 33 and 24 ng . mL(-1) , respectively), but also showed the highest inhibitory effect compared to all other heterodimeric VEGF variants. The high anti-angiogenic potency of this VEGF antagonist may allow its future use as an anti-tumor agent. PMID- 25132002 TI - On fragmenting, densely mineralised acellular protrusions into articular cartilage and their possible role in osteoarthritis. AB - High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-MUm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-MUm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo. PMID- 25132005 TI - Cardiolipin profiles as a potential biomarker of mitochondrial health in diet induced obese mice subjected to exercise, diet-restriction and ephedrine treatment. AB - Cardiolipin (CL) is crucial for mitochondrial energy metabolism and structural integrity. Alterations in CL quantity or CL species have been associated with mitochondrial dysfunction in several pathological conditions and diseases, including mitochondrial dysfunction-related compound attrition and post-market withdrawal of promising drugs. Here we report alterations in the CL profiles in conjunction with morphology of soleus muscle (SM) and brown adipose tissue (BAT) in diet-induced obese (DIO) mice, subjected to ephedrine treatment (EPH: 200 mg kg(-1) day(-1) orally), treadmill exercise (EX: 10 meters per min, 1 h per day), or dietary restriction (DR: 25% less of mean food consumed by the EX group) for 7 days. Mice from the DR and EPH groups had a significant decrease in percent body weight and reduced fat mass compared with DIO controls. Morphologic alterations in the BAT included brown adipocytes with reduced cytoplasmic lipid droplets and increased cytoplasmic eosinophilia in the EX, DR and EPH groups. Increased cytoplasmic eosinophilia in the BAT was ultrastructurally manifested by increased mitochondrial cristae, fenestration of mitochondrial cristae, increased electron density of mitochondrial matrix, and increased complexity of shape and elongation of mitochondria. Mitochondrial ultrastructural alterations in the SM of the EX and DR groups included increased mitochondrial cristae, cup-shaped mitochondria and mitochondrial degeneration. All four CL species (tri-linoleoyl-mono docosahexaenoyl, tetralinoleoyl, tri-linoleoyl-mono-oleoyl, and di-linoleoyl-di oleoyl) were increased in the BAT of the DR and EPH groups and in the SM of the EPH and EX groups. In conclusion, cardiolipin profiling supported standard methods for assessing mitochondrial biogenesis and health, and may serve as a potential marker of mitochondrial dysfunction in preclinical toxicity studies. PMID- 25132004 TI - Outcome of surgery for pancreatic neuroendocrine neoplasms. AB - BACKGROUND: The incidence of pancreatic neuroendocrine neoplasms (pNEN) is increasing. This study aimed to evaluate predictors of overall survival and the indication for surgery. METHODS: Data collected between October 2001 and December 2012 were analysed. Histological grading and staging was based on the classifications of the World Health Organization, the International Union Against Cancer and the European Neuroendocrine Tumour Society. RESULTS: Some 310 patients (150 female, 48.4 per cent) underwent surgical resection. The final survival analysis included 291 patients. Five-year overall survival differed according to tumour grade (G): 91.0 per cent among 156 patients with pancreatic neuroendocrine tumours (pNET) G1, 70.8 per cent in 111 patients with pNET G2, and 20 per cent in 24 patients with pancreatic neuroendocrine carcinomas (pNEC) G3 (P < 0.001). Tumours graded G3 (hazard ratio (HR) 6.96, 95 per cent confidence interval 3.67 to 13.21), the presence of distant metastasis (HR 2.41, 1.32 to 4.42) and lymph node metastasis (HR 2.10, 1.07 to 4.16) were independent predictors of worse survival (P < 0.001, P = 0.004 and P = 0.032 respectively). Eight of 61 asymptomatic patients with pNEN smaller than 2 cm had tumours graded G2 or G3, and six of 51 patients had lymph node metastasis. Among patients with pNEC G3, the presence of distant metastasis had a significant impact on the 5-year overall survival rate: 0 per cent versus 43 per cent in those without distant metastasis (P = 0.036). CONCLUSION: Neuroendocrine tumours graded G3, lymph node and distant metastasis are independent predictors of worse overall survival in patients with pNEN. PMID- 25132003 TI - Integration of geriatric mental health screening into a primary care practice: a patient satisfaction survey. AB - OBJECTIVE: Colocation of mental health screening, assessment, and treatment in primary care reduces stigma, improves access, and increases coordination of care between mental health and primary care providers. However, little information exists regarding older adults' attitudes about screening for mental health problems in primary care. The objective of this study was to evaluate older primary care patients' acceptance of and satisfaction with screening for depression and anxiety. METHODS: The study was conducted at an urban, academically affiliated primary care practice serving older adults. Study patients (N = 107) were screened for depression/anxiety and underwent a post screening survey/interview to assess their reactions to the screening experience. RESULTS: Most patients (88.6%) found the length of the screening to be "just right." A majority found the screening questions somewhat or very acceptable (73.4%) and not at all difficult (81.9%). Most participants did not find the questions stressful (84.9%) or intrusive (91.5%); and a majority were not at all embarrassed (93.4%), upset (93.4%), or uncomfortable (88.8%) during the screening process. When asked about frequency of screening, most patients (72.4%) desired screening for depression/anxiety yearly or more. Of the 79 patients who had spoken with their physicians about mental health during the visit, 89.8% reported that it was easy or very easy to talk with their physicians about depression/anxiety. Multivariate results showed that patients with higher anxiety had a lower positive reaction to the screen when controlling for gender, age, and patient-physician communication. CONCLUSIONS: These results demonstrate strong patient support for depression and anxiety screening in primary care. PMID- 25132006 TI - Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia. AB - It has been reported that certain genetic factors involved in schizophrenia could be located in the mitochondrial DNA (mtDNA). Therefore, we hypothesized that mtDNA mutations and/or variants would be present in schizophrenia patients and may be related to schizophrenia characteristics and mitochondrial function. This study was performed in three steps: (1) identification of pathogenic mutations and variants in 14 schizophrenia patients with an apparent maternal inheritance of the disease by sequencing the entire mtDNA; (2) case-control association study of 23 variants identified in step 1 (16 missense, 3 rRNA, and 4 tRNA variants) in 495 patients and 615 controls, and (3) analyses of the associated variants according to the clinical, psychopathological, and neuropsychological characteristics and according to the oxidative and enzymatic activities of the mitochondrial respiratory chain. We did not identify pathogenic mtDNA mutations in the 14 sequenced patients. Two known variants were nominally associated with schizophrenia and were further studied. The MT-RNR2 1811A > G variant likely does not play a major role in schizophrenia, as it was not associated with clinical, psychopathological, or neuropsychological variables, and the MT-ATP6 9110T > C p.Ile195Thr variant did not result in differences in the oxidative and enzymatic functions of the mitochondrial respiratory chain. The patients with apparent maternal inheritance of schizophrenia did not exhibit any mutations in their mtDNA. The variants nominally associated with schizophrenia in the present study were not related either to phenotypic characteristics or to mitochondrial function. We did not find evidence pointing to a role for mtDNA sequence variation in schizophrenia. PMID- 25132007 TI - Strategic Provider Behavior Under Global Budget Payment with Price Adjustment in Taiwan. AB - Global budget payment is one of the most effective strategies for cost containment, but its impacts on provider behavior have not been explored in detail. This study examines the theoretical and empirical role of global budget payment on provider behavior. The study proposes that global budget payment with price adjustment is a form of common-pool resources. A two-product game theoretic model is derived, and simulations demonstrate that hospitals are expected to expand service volumes, with an emphasis on products with higher price-marginal cost ratios. Next, the study examines the early effects of Taiwan's global budget payment system using a difference-in-difference strategy and finds that Taiwanese hospitals exhibited such behavior, where the pursuit of individual interests led to an increase in treatment intensities. Furthermore, hospitals significantly increased inpatient service volume for regional hospitals and medical centers. In contrast, local hospitals, particularly for those without teaching status designation, faced a negative impact on service volume, as larger hospitals were better positioned to induce demand and pulled volume away from their smaller counterparts through more profitable services and products such as radiology and pharmaceuticals. PMID- 25132008 TI - Malignant mesenchymoma with widespread metastasis including bone marrow involvement in a dog. AB - A male castrated Golden Retriever was presented for evaluation of a large mass over the left shoulder extending to the lower part of the neck that had been present for an extended period of time, but had a recent history of rapid growth. Previous aspirates of the mass were consistent with a lipoma. The mass was surgically excised and was diagnosed as an extraskeletal osteosarcoma based on histopathology. After surgery, the dog was initiated on a chemotherapy protocol with carboplatin and metronomic cyclophosphamide. He became neutropenic, anemic, and thrombocytopenic 14 days after the carboplatin treatment was administered. The neutropenia resolved, but the anemia and thrombocytopenia progressed. A bone marrow aspirate revealed erythroid hypoplasia, myeloid hyperplasia with a predominance of early precursors, and a subset of cells that made up 20% of the total population that were reported as bizarre and unclassifiable. These cells were discrete in nature and were thought to be hematopoietic in origin. The dog was euthanized due to deterioration of the clinical condition. On postmortem examination, widespread metastasis involving the lungs, liver, kidney, heart, and bone marrow was found. Histopathology of the tumor lesions determined 2 distinct malignant populations of liposarcoma and osteosarcoma, consistent with malignant mesenchymoma. However, the possibility of 2 separate neoplastic processes cannot be definitively excluded. This is the first report of bone marrow metastasis of a malignant mesenchymoma in a dog. PMID- 25132009 TI - Isolation and characterization of flagellar filament from zoospores of Dermatophilus congolensis. AB - Highly motile zoospores from Dermatophilus congolensis bovine isolates from clinical dermatophilosis in Japan were obtained by culturing at 27 degrees C in an ambient atmosphere on heart infusion agar supplemented with 5% defibrinated sheep blood for 72h or in heart infusion broth for 48h with gentle shaking. After vigorous mechanical agitation of the zoospore suspension, the flagellar filaments detached from motile zoospores and were isolated in the clear gelatinous part of the final pellet by differential centrifugation. Typical morphology of a flagellar filament, with a width of approximately 15nm, was observed in the isolated flagellar filament by electron microscopy. A single major protein (flagellin) band with an apparent molecular mass of 35kDa was detected in the flagellar filament of D. congolensis strain AM-1 and that of 33kDa was detected in strain IT-2 by SDS-PAGE. In immunoblot analysis of whole-cell proteins from seven isolates of D. congolensis, antiserum to strain AM-1 zoospores reacted with the 35-kDa antigen band of strain AM-1, but not with any antigen band of other strains in a similar molecular mass range. In contrast, antiserum to strain IT-2 zoospores reacted with antigen bands at 33kDa from six strains, except strain AM 1. Similar strain-specific reactions of these anti-zoospore sera with isolated flagellar filaments from strains AM-1 and IT-2 were confirmed by immunoblot, indicating the presence of antigenic variations of flagellins of D. congolensis zoospores. PMID- 25132010 TI - Skeletal effects of bariatric surgery: examining bone loss, potential mechanisms and clinical relevance. AB - Bariatric surgery is the most effective therapeutic approach to morbid obesity, resulting in substantial weight loss and improved cardiometabolic profiles; however, a growing body of evidence suggests that bariatric procedures increase both skeletal fragility and the risk of related future fracture secondary to excessive bone loss. Prospective evidence shows that areal bone mineral density (BMD) assessed by dual energy X-ray absorptiometry (DXA) declines by as much as 14% in the proximal femoral regions, including the femoral neck and total hip, 12 months postoperatively. Lumbar spine areal BMD outcomes show greater 12-month postoperative variability across surgical procedures (-8 to +6%) and contrast with no change in volumetric BMD outcomes measured by quantitative computed tomography. Diminished mechanical loading, micronutrient deficiency and malabsorption, along with neurohormonal alterations, offer plausible underlying mechanisms to explain these observed post-bariatric bone changes, but most remain largely unsubstantiated in this population. Importantly, DXA-based skeletal imaging may have limited utility in accurately detecting bone change in people undergoing bariatric surgery; partly because excessive tissue overlying bone increases the variability of areal BMD outcomes. Moreover, a paucity of fracture and osteoporosis incidence data raises questions about whether marked post bariatric surgery bone loss is clinically relevant or a functional adaptation to skeletal unloading. Future studies that use technology which is able to accurately capture the site-specific volumetric BMD and bone architectural changes that underpin bone strength in people undergoing bariatric surgery, that consider mechanical load, and that better quantify long-term fracture and osteoporosis incidence are necessary to understand the actual skeletal effects of bariatric surgery. PMID- 25132011 TI - A proteomics-based methodology to investigate the protein corona effect for targeted drug delivery. AB - Here we introduce a proteomics methodology based on nanoliquid-chromatography tandem mass spectrometry (nanoLC/MS-MS) to investigate the "protein corona effect for targeted drug delivery", an innovative strategy, which exploits the "protein corona" that forms around nanoparticles in a physiological environment to target cells. PMID- 25132012 TI - Quality of life and illness perception in primary biliary cirrhosis: a controlled cross-sectional study. AB - OBJECTIVE: The aim of this study was to understand better the quality of life (QOL) and illness perception in women with primary biliary cirrhosis (PBC) through a comparison with women having diabetes. METHODS: One hundred and ninety four women took part in this study: 130 with PBC, 64 with type 2 diabetes. They were administered the SF-12 to measure QOL and the Brief Illness Perception Questionnaire to assess representations of their illness. Analysis of covariance with bootstrapping was used to compare QOL and illness perception scores by controlling age and mean disease duration. RESULTS: Physical QOL was significantly worse for women with PBC than for women with diabetes. Women with PBC felt their disease would last longer and reported more symptoms and concerns related to their disease than women with diabetes. Significant differences were also observed for causes: women with PBC mainly reported autoimmune, emotional, unknown/unlucky and medical causes whereas women with diabetes reported mostly lifestyle and hereditary causes. Marginally significant differences were observed regarding consequences on daily life, feeling of control over the disease and emotional responses, which were shown to be worse in PBC. Mental QOL, treatment control and overall understanding of the disease was similar in both groups. CONCLUSIONS: This study shows that women with PBC have a worse QOL and somewhat different illness perception than women with diabetes. Further research could help understand PBC specificities better in order to improve patient care, especially if factors such as fatigue or rarity of the disease explain these results. PMID- 25132013 TI - Psoriasis and sport: a new ally? AB - BACKGROUND: Psoriasis is a common chronic multifactorial disease which can result in restrictions to social and recreational activities. Psoriasis subjects are at high risk to develop metabolic and cardiovascular diseases. Physical activity, a vital component in prevention and management of these diseases, is reported to be potentially associated in a negative way with psoriasis. OBJECTIVE: To investigate the relationship between psoriasis and physical activity. MATERIALS AND METHODS: Anamnestic and physical examination as well as a specific doctor administered questionnaire was performed to a group of 416 consecutive sportive subjects and 489 sex and age-matched controls. Moreover, similar investigations were executed on 400 consecutive psoriatic patients without psoriatic arthritis. RESULTS: Psoriasis was significantly more common in controls respect to sportive group (n = 27, 5.4% vs. n = 7, 1.7%, P < 0.01) whereas a positive familial history of psoriasis was observed in similar percentages in both groups (n = 51, 10.2% vs. n = 40, 9.6%). The number of subjects performing sports activities was significantly lower in psoriasis group compared to controls (n = 44, 11% vs. n = 106, 21.3%; P < 0.001). Of these psoriatic patients, 35/44 referred that sporting activities showed a positive influence on the natural course of their disease, whereas the remaining 11 patients did not highlight positive or negative influences on their illness. Interestingly, 23.75% of psoriatic patients (n = 95) related that they had regularly carried out sporting activities before the onset of the dermatosis referring that psoriasis represented a huge obstacle to continue practicing physical activities. CONCLUSION: Our survey showed that regular physical activity may lower the risk of psoriasis and have a beneficial effect on the natural course of the disease, positively influencing not only the severity as well as the incidence of metabolic comorbidities, but also, through possible epigenomic, metabolic, anti-inflammatory and psycho-emotional effects, the onset of the dermatosis. However, larger birth cohort studies are needed to confirm these results. PMID- 25132014 TI - [Deaths in a Tunisian psychiatric hospital: an eleven-year retrospective study]. AB - BACKGROUND: Mortality in patients in psychiatric hospitals is reported to be two to three times as high as in the general population. In Tunisia, we do not have any figures on mortality and causes of death in psychiatric inpatients. AIM: The aim of our study was to assess the mortality rate in a psychiatric hospital in comparison to the mortality rate in the general population, to determine the patients' profile, and to identify the causes and risk factors for these deaths. METHODS: We performed a retrospective, descriptive and comparative study. We examined the records of all patients who died during their stay in the different wards of psychiatry at the Razi Hospital in Tunis. We also scrutinized reports of autopsies in the Forensic Medicine unit at Charles-Nicolle Hospital in Tunis over a period of eleven years from January 1st, 2000 to December 31st, 2010. We conducted a descriptive study to calculate the standardized mortality ratio (SMR) aiming to highlight any existing excess mortality among the psychiatric inpatients compared to the general population. This ratio was obtained by dividing the observed number of deaths by the expected number of deaths. In the analytical study, our sample was compared to a control population made-up of randomly selected living patients among those admitted to the Razi hospital in 2010. This study allowed us to investigate the risk factors for premature mortality in psychiatric inpatients. RESULTS: The average rate of mortality was two deaths per 1000 inpatients per year. Twenty-four percent (24%) of deaths involved institutionalized patients. Compared to the general population, premature mortality was noted among patients aged less than 40 (SMR=1.9). The older the patients were, the closer to 1 the SMR was. The average age at death was 51.38 years; 65% of patients were male, 60% had a low socio-economic level, 54% had a comorbid medical condition. Forty-two percent (42%) of deceased patients were diagnosed with schizophrenia with the paranoid form being the most prevalent (44%), 13% had bipolar disorder, 22% had psycho-organic disorders (mental retardation, dementia, delirium). Antipsychotics were the most prescribed psychotropic drugs. High doses were used. Forty percent of cases (40%) consisted of sudden deaths. A cause for death was identified in 80% of cases. In 92% of cases, the death was classified as being "natural". Main causes were respiratory (26%) and cardiovascular (9%). Accidental causes accounted for 8% of deaths. In 20% of cases, the cause remained undetermined. Three factors were identified as independent predictors of mortality among mental patients: age at death (OR=3.9 among patients older than 40), psychiatric diagnosis (OR=2.9 among patients with psychotic or mood disorders compared to other diagnoses) and combination of antipsychotic drugs (OR=6.09 in patients receiving more than two antipsychotics). DISCUSSION: Young psychiatric inpatients seem to be at high risk of premature death: the SMR in our study was 1.9. It ranged between 2.15 and 6.55 in other similar studies. This increased risk mainly concerns non-natural deaths. The leading natural cause of death in our population was represented by thromboembolic accidents. Such a high thromboembolic risk may be explained by the mental illness itself, by physical restraint as well as by antipsychotic treatment. Diagnosing medical conditions in psychiatric patients is often a daunting task: history of the patient is sometimes unreliable and clinical features might be modified by psychotropic agents. Patient-related risk factors for premature death include poor socio-economic level, access-to-care difficulties, positive family and personal history of mental and/or medical disorders, smoking, substance abuse, unhealthy diet and lack of physical activity. Moreover, iatrogenic effects of psychotropic drugs (combination of antipsychotics was more common in deceased patients than in controls) and inadequate medical care in psychiatric hospitals (lack of ECG devices, in particular) partly account for such a high mortality. CONCLUSION: Identifying risk factors for deaths in psychiatric hospitals highlights needed changes in psychiatric management strategies taking into account the patient's characteristics as well as the drugs' safety profile. Further studies with larger samples are needed to better highlight risk factors for premature death in psychiatric inpatients. Identifying such risk factors is necessary to develop efficient preventive strategies. PMID- 25132015 TI - [An integrative and transdiagnostic relaxation protocol for anxious patients. Results of a pilot study]. AB - INTRODUCTION: The literature data show that relaxation practice is effective in reducing anxiety symptoms. Different techniques such as progressive muscular relaxation, autogenic training, applied relaxation and meditation have been evaluated independently for anxiety disorders. The question is to know whether the combination of various techniques may be of interest in the transdiagnostic treatment of anxiety disorders. AIM OF THE STUDY: The present study assessed the short-term efficacy of a 10-week integrative and transdiagnostic relaxation program for anxiety disorders in outpatients of an anxiety disorders unit. METHODS: The diagnoses were made according to the Mini-International Neuropsychiatric Interview (MINI; Sheehan et al., 1998) and completed with an assessment of anxiety and depressive symptoms using: the State Trait Anxiety Inventory (STAI-Y, -S and -T), the Penn State Worry Questionnaire (PSWQ) and the Beck Depression Inventory (BDI-II). Four techniques were integrated into the structured 10-week protocol: breathing control, muscular relaxation, meditation and mental visualization. RESULTS: Twenty-eight patients (12 men and 16 women), mean age (S.D.)=38.82 years (11.57), were included in the study. All the included patients fulfilled the DSM-IV criteria for a current diagnosis of Generalized Anxiety Disorder (n=13) or Panic Disorder (n=15) with or without agoraphobia. At the end of the 10 sessions, we found a significant reduction in mean scores (S.D.) on the STAI-T from 53.179 (6.037) to 49.821 (8.028) (P<0.02), the BDI-II 20.964 (13.167) to 15.429 (11.341) (d=0.6543) and the QIPS 55.071 (10.677) to 49.679 (11.7) (d=0.5938). The observed reduction in the STAI-S (d=0.2776) was not significant. DISCUSSION: The results of this open study showed that this program significantly decreases the level of trait anxiety, depression and worry. The integrative and transdiagnostic relaxation program could represent an accessible and effective treatment to reduce anxious and depressive symptoms in various anxiety disorders. Future research should address the development of controlled trials assessing the impact of the different dimensions of anxiety and the long term effects of this protocol. PMID- 25132016 TI - Clinical and molecular characteristics of community-acquired methicillin resistant Staphylococcus aureus infections in Chinese neonates. AB - This study aims to characterize the clinical features of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in Chinese neonates, as well as the molecular characteristics and expression of key virulence genes of isolates. Clinical information and molecular characteristics of 130 cases were analyzed. Up to 83.8% patients were affected with late-onset infection. Cesarean delivery was the main delivery route, accounting for 74.6% of the total deliveries. Pneumonia (69, 53.1%) was the most common infection. A total of 38 patients (29.2%) suffered from complications. Moreover, 35 cases (26.9%) were invasive infections, among which 88.6% involved multiple organs and 45.7% suffered from complications. Cesarean section and premature birth were the risk factors for invasive CA-MRSA infection. ST59-MRSA-SCCmecIVa-t437 (54, 41.5%) was the most predominant CA-MRSA clone. The hla expression in the ST59 isolates was higher than that in ST910 (p = 0.02) and the hla expression in ST59-SCCmecV t437 was higher than that in ST59-SCCmecIVa-t437. Approximately, 46.4% (13/28) of the infections caused by ST59-SCCmecV were invasive. This value is higher than that of ST59-SCCmecVa caused infections (14/59, 23.7%) (p = 0.03). This study showed that neonatal CA-MRSA infections in China readily become invasive, involve multiple organs, and are often accompanied by complications. The SCCmec V clone may be more pathogenic than the SCCmecVIa clone. PMID- 25132017 TI - The rtA181S mutation of hepatitis B virus primarily confers resistance to adefovir dipivoxil. AB - The study aimed to clarify clinical significance of hepatitis B virus (HBV) rtA181S mutation in Chinese HBV-infected patients. A total of 18 419 patients with chronic HBV infection from Beijing 302 Hospital were investigated. HBV complete reverse transcriptase region of polymerase was screened by direct sequencing, and the results were verified by clonal sequencing. Replication competent mutant and wild-type HBV genomic amplicons were constructed and transfected into the HepG2 cells and cultured in the presence or absence of serially diluted nucleos(t)ide analogues. Intracellular HBV replicative intermediates were quantitated for calculating the 50% effective concentration of the drug (EC(50)). The rtA181S was detected in 98 patients with 12 kinds of mutational patterns. Genotype C and genotype B HBV infection occupied 91.8% and 8.2% in rtA181S-positive patients, in contrast to 84.6% and 15.4% in rtA181S negative patients (P < 0.01). All rtA181S-positive patients had received nucleos(t)ide analogues. rtA181S was detected in multiple patients with virologic breakthrough. Phenotypic analysis of patient-derived viral strains showed that rtA181S, rtA181S+N236T, rtN236T and rtA181V strains had 68.5%, 49.9%, 71.4% and 66.2% of natural replication capacity of wild-type strain, and 3.7-fold, 9.8 fold, 7.9-fold and 5.6-fold increased EC(50) to adefovir dipivoxil (ADV). The rtA181S strain remained susceptible to lamivudine, entecavir and tenofovir, and ADV susceptibility was restored after the mutation was eliminated through site directed mutagenesis. Rescue therapy with entecavir or combination therapy was effective in rtA181S-related ADV-refractory patients. The rtA181S mutation confers moderate resistance to ADV. It could be induced by either lamivudine or ADV and contribute ADV treatment failure. PMID- 25132019 TI - Spatiotemporal properties of auditory intensity processing in multisensor MEG. AB - Loudness dependence of auditory evoked potentials (LDAEP) evaluates loudness processing in the human auditory system and is often altered in patients with psychiatric disorders. Previous research has suggested that this measure may be used as an indicator of the central serotonergic system through the highly serotonergic innervation of the auditory cortex. However, differences among the commonly used analysis approaches (such as source analysis and single electrode estimation) may lead to different results. Putatively due to discrepancies of the underlying structures being measured. Therefore, it is important to learn more about how and where in the brain loudness variation is processed. We conducted a detailed investigation of the LDAEP generators and their temporal dynamics by means of multichannel magnetoencephalography (MEG). Evoked responses to brief tones of five different intensities were recorded from 19 healthy participants. We used magnetic field tomography in order to appropriately localize superficial as well as deep source generators of which we conducted a time series analysis. The results showed that apart from the auditory cortex other cortical sources exhibited activation during the N1/P2 time window. Analysis of time courses in the regions of interest revealed a sequential cortical activation from primary sensory areas, particularly the auditory and somatosensory cortex to posterior cingulate cortex (PCC) and to premotor cortex (PMC). The additional activation within the PCC and PMC has implications on the analysis approaches used in LDAEP research. PMID- 25132018 TI - Diagnostic accuracy of C-reactive protein and procalcitonin in the early detection of infection after elective colorectal surgery - a pilot study. AB - BACKGROUND: Colorectal surgery is associated with postoperative infectious complications in up to 40% of cases, but the diagnosis of these complications is frequently misleading, delaying its resolution. Several biomarkers have been shown to be useful in infection diagnosis. METHODS: We conducted a single-centre, prospective, observational study segregating patients submitted to elective colorectal surgery with primary anastomosis, CRP and PCT were measured daily. We compared infected and non-infected patients. RESULTS: From October 2009 to June 2011, a total of 50 patients were included. Twenty-one patients developed infection. PCT and CRP before surgery were equally low in patients with or without postoperative infectious complications. After surgery, both PCT and CRP increased markedly. CRP time-course from the day of surgery onwards was significantly different in infected and non-infected patients (P = 0.001) whereas, PCT time-course was almost parallel in both groups (P = 0.866). Multiple comparisons between infected and non-infected patients from 5th to 9th postoperative days (POD) were performed and CRP concentration was significantly different (P < 0.01, Bonferroni correction), on the 6th, 7th and 8th POD. A CRP concentration > 5.0 mg/dl at the D6 was predictive of infection with a sensitivity of 85% and a specificity of 62% (positive likelihood ratio 2.2, negative likelihood ratio 0.2). CONCLUSIONS: After a major elective surgical insult both CRP and PCT serum levels increased independently of the presence of infection. Besides serum CRP time-course showed to be useful in the early detection of an infectious complication whereas PCT was unhelpful. PMID- 25132022 TI - [Measures of preventing occupational exposure to hazardous drugs-based on new insights]. AB - Little attention has been paid to the hazards that healthcare professionals may be exposed to when administering drugs to patients. Hazardous drugs, even in very low concentrations, can produce adverse reactions in patients and in healthcare professionals who handle the drugs or work in the vicinity. Small amounts of hazardous drugs have been detected in the urine of healthcare professionals who prepare or administer these drugs even with the use of safety protection. Moreover, environmental contamination of hazardous drugs has been reported in a survey of patient care surroundings even when handling guidelines have been followed. The academic subcommittee of the Japanese Society of Hospital Pharmacy has established guidelines for the handling of hazardous drugs; however, reports suggest that there are problems with compliance to the guidelines. Recently, closed system devices have been marketed for use in healthcare settings to reduce environmental contamination during drug preparation. However, these devices have not gained widespread use because of their high cost and incompatibility with certain products like ampules. In addition, it is not clear whether the hazardous drugs are deactivated by these devices. In an effort to prevent healthcare professionals from being exposed to hazardous drugs, it is important to clean up contaminated surfaces and also to prevent dangerous drugs from spreading. PMID- 25132020 TI - Face processing regions are sensitive to distinct aspects of temporal sequence in facial dynamics. AB - Facial movement conveys important information for social interactions, yet its neural processing is poorly understood. Computational models propose that shape- and temporal sequence sensitive mechanisms interact in processing dynamic faces. While face processing regions are known to respond to facial movement, their sensitivity to particular temporal sequences has barely been studied. Here we used fMRI to examine the sensitivity of human face-processing regions to two aspects of directionality in facial movement trajectories. We presented genuine movie recordings of increasing and decreasing fear expressions, each of which were played in natural or reversed frame order. This two-by-two factorial design matched low-level visual properties, static content and motion energy within each factor, emotion-direction (increasing or decreasing emotion) and timeline (natural versus artificial). The results showed sensitivity for emotion-direction in FFA, which was timeline-dependent as it only occurred within the natural frame order, and sensitivity to timeline in the STS, which was emotion-direction dependent as it only occurred for decreased fear. The occipital face area (OFA) was sensitive to the factor timeline. These findings reveal interacting temporal sequence sensitive mechanisms that are responsive to both ecological meaning and to prototypical unfolding of facial dynamics. These mechanisms are temporally directional, provide socially relevant information regarding emotional state or naturalness of behavior, and agree with predictions from modeling and predictive coding theory. PMID- 25132023 TI - [Maintenance therapy for advanced non-small-cell lung cancer]. AB - Maintenance therapy is a new treatment strategy for advanced non-small-cell lung cancer(NSCLC), and it consists of switch maintenance and continuation maintenance.Switch maintenance is the introduction of a different drug, not included as part of the induction therapy, immediately after completion of 4 cycles of first-line platinum-based chemotherapy.Continuation maintenance is a continuation of at least one of the drugs used in the induction therapy in the absence of disease progression.Several phase III trials have reported survival benefits with continuation maintenance of pemetrexed and switch maintenance of pemetrexed or erlotinib.Therefore, maintenance therapy has become a part of the standard first-line treatment for advanced NSCLC.However, further research is needed to elucidate the selection criteria of patients who may benefit the most from maintenance therapy. PMID- 25132024 TI - [Maintenance therapy for colorectal cancer]. AB - Some trials have demonstrated the benefits of maintenance chemotherapy for advanced colorectal cancer. In chemotherapeutic strategies for advanced colorectal cancer, chemotherapy-related toxicity prevention and quality of life(QOL)maintenance are more important than the introduction of a strong regimen, especially when additional surgery is not possible. In Japan, the combination of a folinic acid/5-fluorouracil/oxaliplatin(FOLFOX)regimen and bevacizumab is a popular first-line chemotherapy regimen. However, despite its effectiveness, neuropathy or hand-foot syndrome after 5 or 6 cycles tends to lead to chemotherapy withdrawal. CAIRO3 trial reported the effectiveness of capecitabine and bevacizumab as a maintenance chemotherapy regimen. Additionally, the ML18147 trial demonstrated that bevacizumab beyond progression(BBP)prolonged overall survival(OS)and progression free survival(PFS)in patients with advanced colorectal cancer. Although those trials demonstrated the effectiveness of continuous or maintenance bevacizumab administration, no trials have compared the effectiveness of cytotoxic drugs with bevacizumab as maintenance therapies. Moreover, controversy exists regarding the selection of drugs as a maintenance therapy and the identification of patients who would benefit from maintenance therapy. PMID- 25132021 TI - Heritability of head motion during resting state functional MRI in 462 healthy twins. AB - Head motion (HM) is a critical confounding factor in functional MRI. Here we investigate whether HM during resting state functional MRI (RS-fMRI) is influenced by genetic factors in a sample of 462 twins (65% female; 101 MZ (monozygotic) and 130 DZ (dizygotic) twin pairs; mean age: 21 (SD = 3.16), range 16-29). Heritability estimates for three HM components-mean translation (MT), maximum translation (MAXT) and mean rotation (MR)-ranged from 37 to 51%. We detected a significant common genetic influence on HM variability, with about two thirds (genetic correlations range 0.76-1.00) of the variance shared between MR, MT and MAXT. A composite metric (HM-PC1), which aggregated these three, was also moderately heritable (h(2) = 42%). Using a sub-sample (N = 35) of the twins we confirmed that mean and maximum translational and rotational motions were consistent "traits" over repeated scans (r = 0.53-0.59); reliability was even higher for the composite metric (r = 0.66). In addition, phenotypic and cross trait cross-twin correlations between HM and resting state functional connectivities (RS-FCs) with Brodmann areas (BA) 44 and 45, in which RS-FCs were found to be moderately heritable (BA44: h(2) = 0.23 (sd = 0.041), BA45: h(2) = 0.26 (sd = 0.061)), indicated that HM might not represent a major bias in genetic studies using FCs. Even so, the HM effect on FC was not completely eliminated after regression. HM may be a valuable endophenotype whose relationship with brain disorders remains to be elucidated. PMID- 25132025 TI - [Maintenance therapy in patients with advanced epithelial ovarian cancer-impact of anti-angiogenic molecular targeted agents in progress]. AB - However, in patients with epithelial ovarian cancer, the standard chemotherapy of paclitaxel/carboplatin (TC) therapy is very effective as the overall survival (OS) reached 70-80% in early stage (stage I/II ) patients, in advanced stage patients like stage III/IV the recurrence rate exceeds 80%and the 5-year-OS remains 55%at most. Longer survival remains so worse as well that the 10-year-OS fails to 5-7%. In order to push up the rate of longer survival, the strategies have been considered from the some points of view such as additional new anti cancer agents, changing of drug delivery system (DDS) (i.e. intraperitoneal administration), additional radiotherapy or radioactive agents (in USA), the combination of molecular agents and specific classification in treatment using "Bio-markers (so-called tailor-made medicine)". Here we reviewed the up-coming treatments in maintenance fashion using anti-angiogenic agents or supposing effective and curable treatment by PARP inhibitors in the cohorts of epithelial ovarian cancers with BRCAness. PMID- 25132026 TI - [Current status of adjuvant chemotherapy in patients with p-Stage II and p-Stage III gastric cancer]. AB - The results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS GC)demonstrated that postoperative chemotherapy using S-1 is a standard treatment in Japan for patients with p-Stage II and p-Stage III gastric cancer. We retrospectively reviewed the effect of adjuvant chemotherapy received by 47 patients with p-Stage II and p-Stage III gastric cancer between January 2007 and June 2012. Our hospital is a local university hospital with a high intensive care unit. S-1 monotherapy was administered to 32 patients(adjuvant S-1 group, 68.1%); 22 patients(68.8%)among them completed one year of therapy without any modification to the administration schedule. A total of 8 patients(25.0%)experienced grade 3 adverse events, and 9 patients required a dose reduction, a modification of the administration schedule, or termination of the therapy. S-1 was not administrated to 15 patients(no adjuvant S-1 group, 31.9%); among these patients, 12(80.0%) were not administered S-1 because of their advanced age and comorbidity. The 3-year overall survival rate was 89.3% in the adjuvant S-1 group and 77.1% in the no adjuvant S-1 group. The completion rate of S-1 and survival rate were high for patients in the adjuvant S-1 group, which was similar to the results of the ACTS-GC. However, 25 of 47 patients(53.2%) with p Stage II and p-Stage III gastric cancer did not improve after sufficient adjuvant therapy; therefore, it is important to develop new treatment strategies for these patients. PMID- 25132027 TI - Efficacy of high-dose toremifene therapy in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors:a retrospective, single-institution study. AB - BACKGROUND: Aromatase inhibitors(AI)have established efficacy as first-line therapy in postmenopausal patients with hormone-sensitive metastatic breast cancer(MBC). However,the use of endocrine therapy has not yet been established for second-line and later therapy. Our study examined the efficacy of high-dose toremifene therapy(HD-TOR)in patients with MBC resistant to AIs. PATIENTS AND METHODS: A retrospective analysis was carried out to determine outcomes in 85 postmenopausal patients with MBC resistant to AIs who began HD-TOR between May 2001 and October 2011. The patients received toremifene 120 mg once daily on consecutive days. RESULTS: The objective response rate(ORR)was 21.2%,the clinical benefit rate(CBR)was 41.2%,and the median time to treatment failure(TTF)was 7.3 months. The CBR was high in patients with ER-positive status(p=0.045),no visceral metastasis(p=0.037),HD -TOR as first- or second-line therapy(p=0.007),no history of tamoxifen(TAM)therapy(p=0.019),and no history of chemotherapy(p=0.017). Multivariate analysis showed that ER-positive status(p=0.005, odds ratio: 0.064)and no visceral metastasis(p=0.034, odds ratio: 0.323)were independent predictors of efficacy. The TTF was significantly longer in patients with ER positive status(p=0.019)and no history of TAM therapy(p=0.015). Multivariate analysis showed that ER-positive status(p=0.025, hazard ratio: 0.377)and no history of TAM therapy(p=0.002, hazard ratio: 0.422)were independent predictors of efficacy. No patient discontinued HDTOR therapy due to adverse events. CONCLUSION: HD-TOR is an effective endocrine therapy for patients with MBC who have failed AIs. PMID- 25132028 TI - [Examination of a relapsing pattern of cases of completely resected non-small cell lung cancer]. AB - PURPOSE: The purpose of this research was to understand the clinical discovery of a relapse, relapse time, and the presentation of the first relapse of non-small cell lung cancer(NSCLC)by examining cases of relapse after complete resection of NSCLC. Objective and method. Cases of relapse after complete resection of NSCLC in our hospital were examined. RESULTS: Fifteen cases were evaluated. In half of these cases, relapse was discovered owing to increased tumor marker values. Of the patients, 60%had a relapse within 2 years after resection and 20%had a relapse 5 years after resection. The first relapse was a local recurrence in 9 cases, lung metastasis in 5 cases, and distant metastasis outside the thoracic cavity in 3 cases. CONCLUSION: The effectiveness of the tumor marker as a diagnostic parameter of relapse in NSCLC was demonstrated. Discovering distant metastases at the early postoperative period and relapse 5 years after resection are important. PMID- 25132029 TI - [Analysis of factors influencing the occurrence of infusion reaction after initial treatment with rituximab]. AB - We investigated factors influencing the occurrence of infusion reactions after initial treatment with rituximab. We included patients who were administered rituximab for the treatment of B-cell non-Hodgkin's lymphoma at the Gifu Municipal Hospital Hematology from February 2010 to March 2013. Fifty-one patients were included; their median age was 72(44-87)years, and 31 were men and 20 were women. We defined the index of infusion reaction as the maximal change in body temperature within 24 hours from the administration of rituximab and evaluated the correlation with change in body temperature and each factor, and differences of change in body temperature between the upper and lower groups divided by standard value of each factor by using the t test without correspondence. The "2,000 U/mL or less group"of soluble interleukin-2 receptor(sIL- 2R)levels and the "over 2,000 U/mL group"showed significant different(p=0.014). The "double value or less group"of a standard value(211 IU/L)and "over double value group"showed significantly different lactate dehydrogenase(LDH)levels (p=0.017). The "lower limit or less group"of the standard value(men: 13 g/dL, women: 12 g/dL)and the "over lower limit group"showed significantly different hemoglobin(Hb)levels(p=0.020). In conclusion, the levels of sIL-2R, LDH, and Hb may predict the occurrence of infusion reaction after the initial administration of rituximab in patients with B-cell non-Hodgkin's lymphoma. PMID- 25132030 TI - [Subcutaneous implantation type central venous port management in patients with malignant tumors effect of different antiseptic agents on central venous port related infection]. AB - Subcutaneous implantation type central venous ports(CV ports)are used in chemotherapy. Here, we prospectively examined the frequency of CV port-related infections when the disinfectant was changed from 10% povidone iodine to 1% chlorhexidine ethanol or 70% ethanol. The subjects were patients with malignant tumors, who had newly been implanted with CV ports. We examined CV port-related infections at 1 week after CV port implantation and every 2 weeks thereafter, following sterilization upon insertion of a Huber needle to the CV port. CV port evulsion due to CV port-related infection was noted in 3 patients(4.8%)in whom 15%chlorhexidine ethanol was used(n=62)and in 2 patients(3.3%)in whom 70% ethanol was used(n=60). Infection rates per 1,000 days of CV port use were 1.48% and 1.01%, respectively. Thus, the outcomes of sterilization using 1% chlorhexidine ethanol and 70% ethanol did not differ significantly from those on using 10% povidone iodine for sterilization, based on preliminary results at our institution(3 of 59 patients[5.1%]had port evulsion due to CV port-related infection and the infection rate per 1,000 days of CV port use was 1.47%, Akahane et al, 2012). Chlorhexidine ethanol and ethanol are very convenient to use because they dry quickly and do not need discoloration. Accordingly, chlorhexidine ethanol and ethanol might be useful in CV port management. PMID- 25132031 TI - [Relation between pain and health-related quality of life in cancer patients]. AB - PURPOSE: This study aimed to investigate the relation between pain and health related quality of lif e(HRQOL)in cancer patients. METHODS: An internet-based HRQOL survey of 618 patients with different malignancies using the EORTC QLQ-C30 and BPI-SF was performed. Three study groups were formed based on the pain in the previous month: group A comprised patients without pain; group B comprised patients with mild pain; and group C comprised patients with moderate to severe pain. RESULTS: Compared with both groups A and B, group C had significantly low global HRQOL and functioning, which resulted in fatigue, dyspnea, disturbed sleep, and financial difficulties. In addition, the patients in group C were significantly dissatisfied with their cancer medical service compared with the patients in both groups A and B. CONCLUSION: Pain is an important health issue that not only negatively affects the HRQOL but also results in fatigue, dyspnea, disturbed sleep, and financial difficulties in cancer patients. These symptoms may be important key words for HRQOL analysis in clinician-patient interviews. PMID- 25132032 TI - [A case of malignant peritoneal mesothelioma diagnosed with laparoscopic biopsy]. AB - A 66-year-old woman was admitted to our hospital for massive ascites of unknown origin. Peritoneal mesothelioma was suspected because of her history of asbestos exposure. Diagnostic laparoscopy with biopsy of the peritoneum and greater omentum was performed. Pathological examination with immunostaining provided a definite diagnosis of malignant peritoneal mesothelioma. The patient underwent early postoperative induction therapy with pemetrexed and carboplatin, which resulted in a reduction in ascites. Laparoscopic biopsy contributed to the definite diagnosis of malignant peritoneal mesothelioma, and thereby, early induction of chemotherapy. PMID- 25132033 TI - [A case of syndrome of inappropriate antidiuretic hormone secretion in a patient with esophageal carcinoma possibly induced by cisplatin in neoadjuvant chemotherapy]. AB - A 60 -year-old man complained of dysphagia and was admitted to our hospital for adjuvant chemotherapy under a diagnosis of esophageal carcinoma(squamous cell carcinoma[SCC], Stage II ). He was treated with cisplatin(CDDP)and 5- fluorouracil(5-FU). On the fifth day after administration, he experienced mild disorientation, and early morning on the sixth day, he showed impaired consciousness. Laboratory studies revealed a serum sodium level of 111mEq/L and a serum chloride level of 73mEq/L. The findings of computed tomography and magnetic resonance imaging of the head were unremarkable. Other laboratory studies revealed a plasma vasopressin level of 19.2 pg/mL, a plasma osmolality of 219mOsm/kg, a serum creatinine level of 0.61mg/dL, a serum cortisol level of 27.1 mg/dL, a urine osmolality of 665mOsm/kg, and a urine sodium level of 157.1mEq/L. There were no signs of dehydration, and so the patient was diagnosed with syndrome of inappropriate antidiuretic hormone secretion(SIADH). We discontinued chemotherapy and initiated fluid restriction and sodium supplementation. After this treatment, the patient's consciousness progressively improved. On the fifth day of treatment, laboratory studies revealed a serum sodium level of 138mEq/L and a serum chloride level of 98mEq/L, indicating recovery from hyponatremia. PMID- 25132034 TI - [A case of gastric cancer with N2 lymph node metastasis and pancreatic invasion effectively treated with docetax-el/S-1 as a neoadjuvant chemotherapy]. AB - A 74-year-old man was diagnosed with advanced gastric cancer(cStage III B). Laparotomy showed N2 lymph node metastasis and pancreatic invasion. Radical resection appeared impossible and was thus not performed. Chemotherapy consisting of a combination of S-1(80mg/m 2, 2-week administration and 1-week rest), and docetaxel(40mg/m2day 1)was administered with the expectation of tumor downstaging. A partial response(PR)was obtained after five courses of this regimen in which the primary lesion and lymph node swelling remarkably improved. Total gastrectomy, splenectomy, partial colectomy, and D2 lymph node dissection were then performed. Pathological analysis revealed very few cancer cells in the primary lesion and that the lymph nodes had become scarred and fibrotic. The histological appearance was judged to be grade 2 and the final diagnosis was T1N0H0P0CY0M0, fStage I A, curability A. Currently, more than 6 years and 4 months after the operation, the patient is alive without any evidence of recurrence. Thus, docetaxel/S-1 combination therapy was an effective neoadjuvant chemotherapy for this case of advanced gastric cancer. PMID- 25132035 TI - [A case of advanced gastric cancer with multiple liver metastases treated with preoperative TS-1/CDDP chemotherapy and resection, with a complete response and survival for 7 years]. AB - CASE: An 82-year-old man died because of squamous cell carcinoma of the right lung with metastasis to the left femoral bone. At the age of 75 years, he was admitted to our hospital because of hematemesis. Widespread type 3 gastric cancer was detected in the lesser curvature. Computed tomography(CT)showed multiple liver metastases. Preoperative chemotherapy with TS-1/cisplatin(CDDP)was administered. TS-1 was orally administered at 80mg/body/day and CDDP was administered by intravenous infusion at 20mg/body/day every week for 3 weeks and this was followed by a drug-free 2-week period as the first course. After the fourth course, gastrectomy was performed for the primary lesion and radiofrequency ablation(RFA)was performed for the liver metastases. The patient survived for more than 7 years with a complete response (CR)and died thereafter because of squamous cell carcinoma of the lung. PMID- 25132036 TI - [A case of disseminated carcinomatosis of the bone marrow with disseminated intravascular coagulation caused by advanced colon cancer successfully treated with SOX/bevacizumab]. AB - Our patient was a 58-year-old man who was diagnosed with a large bowel obstruction caused by ascending colon cancer, together with multiple liver metastases for which a right hemicolectomy was performed. After the operation, he developed disseminated intravascular coagulation(DIC)and severe anemia. Bone marrow biopsy findings led to a diagnosis of disseminated carcinomatosis of the bone marrow caused by colon cancer. We administered S-1+oxaliplatin(SOX) and bevacizumab( BV)chemotherapy, which improved the DIC. The patient was discharged from the hospital. After a total of six courses of chemotherapy, the carcinoma became resistant. We changed the drug regimen and his clinical condition improved. He survived for 292 days from the onset of disease. PMID- 25132037 TI - [A case of a patient with advanced rectal cancer and urinary bladder fistula surviving for 6 years after chemoradiotherapy without surgery]. AB - A 60-year-old man with advanced rectal cancer and urinary bladder fistula received preoperative chemoradiotherapy with S-1(120mg/m / 2day)on weekdays and concurrent radiotherapy(65 Gy). After chemoradiotherapy, the clinical symptoms resolved and the tumor shrunk, as observed on endoscopic and radiologic examinations. However, remnant cancer was suspected; therefore, modified oxaliplatin, 5-fluorouracil, and Leucovorin(mFOLFOX6)therapy was initiated, although it was stopped after 3 cycles because of numbness in the lower extremities. Finally, clinical and pathological complete response(CR) was achieved by administering additional doses of S-1 for approximately 1 year after treatment initiation; CR was confirmed by using endoscopy and computed tomography(CT), and there has been no recurrence for 6 years. This case suggests that treatment without surgery is a viable alternative for advanced rectal cancer with pathological CR after chemoradiotherapy. PMID- 25132038 TI - [Gallbladder cancer with elevated serum alpha-fetoprotein, alpha-fetoprotein-L3, and human chorionic gonadotropin levels]. AB - A 61-year-old woman presented with fever and was diagnosed with choledocholithiasis, which was removed endoscopically. Incidentally, a markedly elevated serum alpha-fetoprotein(AFP)level was detected(1,951 ng/mL), but computed tomography( CT)showed only diffuse gallbladder wall thickening. Subsequently, markedly elevated serum AFP-L3 and human chorionic gonadotropin(HCG)levels were detected(99.6%and 2,867mIU/mL, respectively). Fluorodeoxyglucose(FDG)- positron emission tomography/CT demonstrated high FDG uptake only in the gallbladder. Gallbladder cancer was suspected and the patient was scheduled for a cholecystectomy. However, CT just prior to surgery revealed multiple liver metastases. Percutaneous gallbladder biopsy revealed a moderately differentiated adenocarcinoma positive for AFP but not HCG. The patient underwent chemotherapy consisting of gemcitabine and cisplatin. A CT scan obtained 12 weeks later showed disease progression and AFP and HCG levels were found to have increased to 4,021 ng/mL and 66,000mIU/mL, respectively. Although immunohistochemistry of biopsy specimen did not demonstrate HCG production, increased serum HCG level on disease progression definitely suggested HCG production of gallbladder cancer. We believe the biopsy specimen was very small and therefore did not prove HCG production. Gallbladder cancer with simultaneous production of AFP and HCG is rare, and we therefore report this case together with a review of the literature. PMID- 25132039 TI - [A case of locally advanced and metastatic breast cancer successfully treated with combination therapy of paclitaxel and bevacizumab]. AB - The patient was a 53-year-old woman with a large left breast tumor. Triple negative breast cancer with bilateral axillary lymph-node metastasis and bone metastasis was diagnosed. The primary treatment consisted of chemotherapy with a combination of paclitaxel(PTX 80mg/m 2)and bevacizumab(Bev 10 mg/kg). After chemotherapy, the tumor shrunk and showed an obvious decrease in size, eventually disappearing. After therapy, an ulcer was detected on the left breast, and mastectomy and axillary lymph node dissection were performed. The patient's postoperative course was uneventful and she has been receiving chemotherapy at our outpatient clinic. Thus, combination therapy with PTX and Bev may be useful for the local control of advanced breast cancer. PMID- 25132040 TI - [A case and literature review of ovarian carcinosarcoma with long-term survival after repeated recurrences]. AB - Ovarian carcinosarcoma is a rare and aggressive tumor with a poor prognosis. We report a case of ovarian carcinosarcoma and also review the literature. In 2000, a 63-year-old woman underwent optimal cytoreductive surgery for ovarian carcinosarcoma( International Federation of Gynaecology and Obstetrics[FIGO]stage III c[pT3cN0M0]). She received adjuvant chemotherapy with paclitaxel and carboplatin(TC). In 2005, a recurrent tumor was noted anterior to the sacrum. The patient had a complete response after 6 cycles of TC chemotherapy; however, a year later, the tumor recurred and was resected. In 2013, the tumor recurred adjacent to the right kidney and was surgically removed after a partial response to 3 cycles of TC chemotherapy. The pathologic findings included epithelial and non-epithelial components with histologic variation and differentiation; specifically, a leiomyosarcoma, cartilaginous tissues with cellular atypia, and a rhabdomyosarcoma were identified in specimens obtained during the first, second, and third surgical procedures, respectively. In keeping with the combination theory of histogenesis, the ovarian carcinosarcoma described herein may have originated from a monoclonal stem cell. The long survival of this patient is attributed to optimal cytoreduction during the primary operation, solitary recurrent tumors that were completely resected, and sensitivity to chemotherapy. PMID- 25132041 TI - [A case of a large liposarcoma of the chest]. AB - A49 -year-old woman with a growing tumor of the left anterior chest wall was admitted to our hospital. This patient was diagnosed with a malignant well differentiated tumor by needle biopsy and underwent surgery involving wide resection of the tumor, associated excision of the major pectoralis muscle, and part of the mammary tissue and skin. The tumor measured 14.2*17.8 cm and weighed 1,220 g. Histopathologically, the tumor was confirmed to be a dedifferentiated liposarcoma, and local recurrence and metastasis often occurs in spite of complete surgical resection. However, no local recurrence or metastasis has been detected 2 months post-surgery. The main anatomic sites of liposarcomas are the retroperitoneum and lower extremities; only 19 liposarcoma cases of the anterior chest wall have been reported in Japan. PMID- 25132043 TI - Reversal of Type 2 diabetes after bariatric surgery is determined by the degree of achieved weight loss in both short- and long-duration diabetes. AB - AIM: To define the impact of duration of diabetes and extent of weight loss on the reversibility of Type 2 diabetes after bariatric surgery. METHODS: Complete data were collated from 89 individuals with Type 2 diabetes mellitus undergoing any bariatric surgical procedure in a specialist bariatric centre. People with a preoperative HbA1c < 43 mmol/mol (6.1%) were excluded. Diabetes duration was defined as: short, < 4 years; medium, 4-8 years; and long, > 8 years. RESULTS: An HbA1c of <43 mmol/mol (6.1%) was achieved by 62% of patients in the short duration group and 26% of patients in the long-duration group. Normoglycaemia was rarely achieved in the long-duration group if weight loss was < 25 kg. In the whole cohort there was a clear relationship of greater weight loss with lower HbA1c levels (Rs = -0.53; P < 0.0001). CONCLUSIONS: The study shows that the degree of achieved weight loss is the major determinant of return to normal blood glucose levels after bariatric surgery. Normoglycaemia can be achieved in long duration Type 2 diabetes, but a greater degree of weight loss is required than for short-duration diabetes. PMID- 25132042 TI - [Effective treatment of metastatic rhabdomyosarcoma with pazopanib]. AB - Pazopanib, an oral tyrosine kinase inhibitor, is the first molecular-targeted agent approved for the treatment of advanced soft tissue sarcoma(STS). Rhabdomyosarcoma in adults is rare, accounting for less than 3%of all adult STS cases. A 57-year old woman presented with cervical lymphadenopathy. Computed tomography revealed a heterogeneous mass in the retroperitoneum, replacing the entire right kidney. On the basis of the above findings, the patient was diagnosed with alveolar rhabdomyosarcoma. She was first treated with 4 courses of vincristine, actinomycin D, and cyclophosphamide(VAC), which resulted in a partial response. Dose reduction and delay occurred owing to hematological toxicity and febrile neutropenia. As second-line chemotherapy, the patient was administered a single daily dose of 800 mg of pazopanib. Because of an episode of hand-foot syndrome and hepatic impairment, the 800-mg daily dose of pazopanib was reduced to a daily dose of 600 mg, which had to be further reduced to a daily dose of 400 mg owing to fatigue and anorexia. The patient maintained a partial response for a total of 4.3 months when treated with pazopanib. Therefore, this drug may be a new treatment option for patients showing metastatic STS after previous chemotherapy. PMID- 25132044 TI - Echocardiographic and clinical response to cardiac resynchronization therapy in heart failure patients with and without previous right ventricular pacing. AB - AIMS: Right ventricular pacing (RVp) results in an electrocardiographic left bundle branch block pattern and can lead to heart failure. This study aimed to evaluate echocardiographic and clinical outcomes of heart failure patients with RVp upgraded to cardiac resynchronization therapy (CRT), as they are frequently excluded from multicentre studies. METHODS AND RESULTS: This observational study assessed 655 consecutive patients with QRS >=120 ms and left ventricular ejection fraction <=35%. There were 465 patients without significant previous RVp and 190 with RVp >40%. Echocardiograms were analysed pre-CRT and ~ 1 year post-CRT. Death and heart failure hospitalizations were analysed using Cox regression, adjusted for baseline characteristics. The RVp patients had smaller end-systolic volume (P = 0.002), were older (P < 0.001), and had more atrial fibrillation (P < 0.001) pre-CRT. Ejection fraction and proportion of ischaemic aetiology were similar. One year following CRT implantation the ejection fraction response was greater in the RVp group (8.3 +/- 9 vs. 5.8 +/- 9 units, P = 0.005). The RVp patients had an adjusted 33% lower risk of death or heart failure hospitalization [hazard ratio (HR) 0.67 95% confidence interval (CI) 0.51-0.89, P = 0.005], while tending to have an adjusted lower risk of death (HR 0.73 95% CI 0.53-1.01, P = 0.055). CONCLUSION: Despite similar ejection fraction pre-CRT, patients upgraded to CRT with previous RVp have smaller end-systolic volume and respond to CRT at least as well as, if not better than, other wide QRS heart failure patients. A greater improvement in ejection fraction and a lower risk of death or heart failure hospitalization when adjusted for baseline characteristics were seen in those with previous RVp. PMID- 25132045 TI - Sublethal effects of the beta-blocker sotalol at environmentally relevant concentrations on the New Zealand mudsnail Potamopyrgus antipodarum. AB - Monitoring sublethal effects of pharmaceuticals on nontarget species in aquatic environments has become an important topic in ecotoxicology, yet few studies have been conducted concerning the effects of beta-blockers on aquatic organisms. The present study investigated the effects of the beta-blocker sotalol (SOT) at 3 environmentally relevant concentrations on life-history traits of the New Zealand mudsnail Potamopyrgus antipodarum. Based on the pharmacodynamic properties of SOT, the authors hypothesized reduced numbers of embryos in the brood pouches, decelerated growth of adult snails, and smaller size of neonates, but no effect on mortality rates of adults. Contrary to the hypothesis, the total number of embryos was significantly higher after 56 d of exposure at nominal concentrations of 0.05 ug/L and 1.0 ug/L by 107% and 73%, respectively. No differences in embryo numbers were observed at earlier time-points. Therefore, the mode of action seems to be an extension of the reproductive period rather than an increase of the embryo production. Furthermore, our results indicate a hormetic dose-response relationship, because no effects were observed at the highest test-concentration (6.5 ug/L). Mortality, growth of adult snails, and neonate sizes were not affected by the beta-blocker. Given the strong influence on reproduction, the effects of sublethal concentrations of SOT and other beta-blockers deserve better consideration in ecotoxicological risk assessment. PMID- 25132047 TI - Salt-stress induced modulation of chlorophyll biosynthesis during de-etiolation of rice seedlings. AB - Chlorophyll biosynthesis in plants is subjected to modulation by various environmental factors. To understand the modulation of the chlorophyll (Chl) biosynthesis during greening process by salt, 100-200 mM NaCl was applied to the roots of etiolated rice seedlings 12 h prior to the transfer to light. Application of 200 mM NaCl to rice seedlings that were grown in light for further 72 h resulted in reduced dry matter production (-58%) and Chl accumulation ( 66%). Ionic imbalance due to salinity stress resulted in additional downregulation (41-45%) of seedling dry weight, Chl and carotenoid contents over and above that of similar osmotic stress induced by polyethylene glycol. Downregulation of Chl biosynthesis may be attributed to decreased activities of Chl biosynthetic pathway enzymes, i.e. 5-aminolevulinic acid (ALA) dehydratase (EC-2.4.1.24), porphobilinogen deaminase (EC-4.3.1.8), coproporphyrinogen III oxidase (EC-1.3.3.3), protoporphyrinogen IX oxidase (EC-1.3.3.4), Mg protoporphyrin IX chelatase (EC-6.6.1.1) and protochlorophyllide oxidoreductase (EC-1.3.33.1). Reduced enzymatic activities were due to downregulation of their protein abundance and/or gene expression in salt-stressed seedlings. The extent of downregulation of ALA biosynthesis nearly matched with that of protochlorophyllide and Chl to prevent the accumulation of highly photosensitive photodynamic tetrapyrroles that generates singlet oxygen under stress conditions. Although, ALA synthesis decreased, the gene/protein expression of glutamyl-tRNA reductase (EC-1.2.1.70) increased suggesting it may play a role in acclimation to salt stress. The similar downregulation of both early and late Chl biosynthesis intermediates in salt-stressed seedlings suggests a regulatory network of genes involved in tetrapyrrole biosynthesis. PMID- 25132046 TI - Analysis of genetic mutations in Chinese patients with systemic primary carnitine deficiency. AB - Systemic primary carnitine deficiency (CDSP) is caused by mutations in SLC22A5 gene, which encodes organic cation transporter 2(OCTN2). CDSP leads to skeletal or cardiac myopathy and hepatic encephalopathy. The present study aimed to identify SLC22A5 gene mutations and analyze the potential relationship between genotype and clinical symptoms in 20 Chinese patients with CDSP. The complete coding region of the SLC22A5 gene including intron-exon boundaries were amplified and sequenced in all patients. Eighteen different mutations were found; of which, nine were novel. The mutations clustering in exons 1 and 4 accounted for 66.7% of all mutant alleles (26/39). The c.760C>T (p. R254X) was the most frequent mutation (25.6%, 10/39), suggesting it as an ethnic founder mutation. The relationship between genotype and phenotype was investigated in patients carrying the R254X mutation. Homozygous patients with R254X were late-onset cases who presented with dilated cardiomyopathy and muscle weakness after 1 year of age. Compound heterozygous patients carrying R254X, combined with other missense mutations occurred in very specific positions, dramatically altered OCTN2 protein function. Based on the analysis of case studies, a clear relationship between free carnitine (C0) level in plasma and OCTN2 genotype was not found in the present work, however, the low plasma C0 level could not indicate disease severity or genotype. Further functional studies with a large sample size are required to understand the relationship between R254X mutation and CDSP. PMID- 25132048 TI - Effects of developmental methylphenidate (MPH) treatment on monoamine neurochemistry of male and female rats. AB - Attention Deficit Hyperactivity Disorder (ADHD) is estimated to affect 4-5% of the adult human population (Kessler et al., 2006; Willcutt, 2012). Often prescribed to attenuate ADHD symptoms (Nair and Moss, 2009), methylphenidate hydrochloride (MPH) can have substantial positive effects. However, there is a paucity of literature regarding its use during pregnancy. Thus, adult women with ADHD face a difficult decision when contemplating pregnancy. In this study, pregnant Sprague-Dawley rats were orally treated a total of 0 (water), 6 (low), 18 (medium), or 42 (high) mg MPH/kg body weight/day (divided into three doses) on gestational days 6-21 (i.e., the low dose received 2 mg MPH/kg body weight 3*/day). Offspring were orally treated with the same daily dose as their dam (divided into two doses) on postnatal days (PNDs) 1-21. One offspring/sex/litter was sacrificed at PND 22 or PND 104 (n=6-7/age/sex/treatment group) and the striatum was quickly dissected and frozen. High Performance Liquid Chromatography (HPLC) coupled to a Photo Diode Array detector (PDA) was used to analyze monoamine content in the striatum of one side while a sandwich ELISA was used to analyze tyrosine hydroxylase (TH) from the other side. Age significantly affected monoamine and metabolite content as well as turnover ratios (i.e., DA, DOPAC, HVA, DOPAC/DA, HVA/DA, 5-HT and 5-HIAA); however, there were no significant effects of sex. Adult rats of the low MPH group had higher DA levels than control adults (p<0.05). At both ages, subjects of the low MPH group had higher TH levels than controls (p<0.05), although neither effect (i.e., higher DA or TH levels) exhibited an apparent dose-response. PND 22 subjects of the high MPH treatment group had higher ratios of HVA/DA and DOPAC/DA than same-age control subjects (p<0.05). The increased TH levels of the low MPH group may be related to the increased DA levels of adult rats. While developmental MPH treatment appears to have some effects on monoamine system development, further studies are required to determine if these alterations manifest as functional changes in behavior. PMID- 25132050 TI - The development of a classification schema for arts-based approaches to knowledge translation. AB - BACKGROUND: Arts-based approaches to knowledge translation are emerging as powerful interprofessional strategies with potential to facilitate evidence uptake, communication, knowledge, attitude, and behavior change across healthcare provider and consumer groups. These strategies are in the early stages of development. To date, no classification system for arts-based knowledge translation exists, which limits development and understandings of effectiveness in evidence syntheses. PURPOSE: We developed a classification schema of arts based knowledge translation strategies based on two mechanisms by which these approaches function: (a) the degree of precision in key message delivery, and (b) the degree of end-user participation. We demonstrate how this classification is necessary to explore how context, time, and location shape arts-based knowledge translation strategies. DISCUSSION: Classifying arts-based knowledge translation strategies according to their core attributes extends understandings of the appropriateness of these approaches for various healthcare settings and provider groups. The classification schema developed may enhance understanding of how, where, and for whom arts-based knowledge translation approaches are effective, and enable theorizing of essential knowledge translation constructs, such as the influence of context, time, and location on utilization strategies. LINKING EVIDENCE TO ACTION: The classification schema developed may encourage systematic inquiry into the effectiveness of these approaches in diverse interprofessional contexts. PMID- 25132051 TI - Neonicotinoids and bumblebees (Bombus terrestris): effects on nectar consumption in individual workers. AB - BACKGROUND: The objective of this study was to quantify whether the presence of three different neonicotinoid insecticides (imidacloprid, thiamethoxam or clothianidin) in sucrose solution results in antifeedant effects in individual worker bumblebees (Bombus terrestris), and, if so, whether this effect is reversible if bees are subsequently offered untreated feed. RESULTS: Bees exposed to imidacloprid displayed a significant dose-dependent reduction in consumption at 10 and 100 ug L(-1), which was reversed when untreated feed was offered. No consistent avoidance/antifeedant response to nectar substitute with thiamethoxam was detected at the more field-realistic dose rates of 1 and 10 ug L(-1), and exposure to the very high 100 ug L(-1) dose rate was followed by 100% mortality of experimental insects. No reduction in food intake was recorded at 1 ug clothianidin L(-1), reduced consumption was noted at 10 ug clothianidin L(-1) and 100% mortality occurred when bees were exposed to rates of 100 ug clothianidin L( 1). CONCLUSION: This study provides evidence of a direct antifeedant effect of imidacloprid and clothianidin in individual bumblebees but highlights that this may be a compound-specific effect. PMID- 25132052 TI - A photoswitchable bis-azo derivative with a high temporal resolution. AB - The novel photoswitchable bis-azo derivative reported herein shows a high temporal resolution of 2 * 10(8) times between the thermal relaxation rates of its two constituting photochromes. Moreover, the slow and fast azo building blocks of this molecular construct can be triggered by using UV and visible light, respectively. PMID- 25132053 TI - Butterfly-shape scalp excision: a single stage surgical technique for cutis verticis gyrata. PMID- 25132054 TI - Response to 'Uterine fundal pressure: is it really a culprit of poor maternal and neonatal outcome?' by Shigeki Matsubara. PMID- 25132056 TI - Part one: for the motion. Venous perforator surgery is proven and does reduce recurrences. PMID- 25132049 TI - A-kinase anchoring proteins: cAMP compartmentalization in neurodegenerative and obstructive pulmonary diseases. AB - The universal second messenger cAMP is generated upon stimulation of Gs protein coupled receptors, such as the beta2 -adreneoceptor, and leads to the activation of PKA, the major cAMP effector protein. PKA oscillates between an on and off state and thereby regulates a plethora of distinct biological responses. The broad activation pattern of PKA and its contribution to several distinct cellular functions lead to the introduction of the concept of compartmentalization of cAMP. A-kinase anchoring proteins (AKAPs) are of central importance due to their unique ability to directly and/or indirectly interact with proteins that either determine the cellular content of cAMP, such as beta2 -adrenoceptors, ACs and PDEs, or are regulated by cAMP such as the exchange protein directly activated by cAMP. We report on lessons learned from neurons indicating that maintenance of cAMP compartmentalization by AKAP5 is linked to neurotransmission, learning and memory. Disturbance of cAMP compartments seem to be linked to neurodegenerative disease including Alzheimer's disease. We translate this knowledge to compartmentalized cAMP signalling in the lung. Next to AKAP5, we focus here on AKAP12 and Ezrin (AKAP78). These topics will be highlighted in the context of the development of novel pharmacological interventions to tackle AKAP-dependent compartmentalization. PMID- 25132057 TI - Part two: against the motion. Venous perforator surgery is unproven and does not reduce recurrences. PMID- 25132055 TI - An historical perspective on health-risk awareness and unhealthy behaviour: cigarette smoking in the United States 1949-1981. AB - OBJECTIVE: This paper investigates the change through time in the perception of smoking-related health harm and smoking behaviour from 1949 to 1981. BACKGROUND AND CONTEXT: A variety of common behaviours can be linked to chronic disease risk smoking, over-eating, and excessive sitting, to name a few. Changing behaviours to reduce exposure to such risks can be an effort that spans generations and decades. SETTING AND PARTICIPANTS: Respondents to Gallup Poll surveys in the United States from 1949, 1954, 1957, 1971, 1972, 1977 and 1981. METHODS: Graphical analysis and probit regression are used to investigate trends through time and statistical associations of smoking with the perception of smoking related health risks and other socio-demographic variables. INTERVENTION AND MAIN VARIABLE STUDIED: Perceived smoking health risk. MAIN OUTCOME MEASURE: Smoking participation. RESULTS AND CONCLUSION: Our findings include the proportions of individuals who were self-reported smokers fell between 1949 and 1981, from 0.48 to 0.34. Among smokers, the proportion who believed smoking was harmful increased from 0.52 in 1949 to 0.81 in 1981. By 1981, the proportion of non-smokers who believed smoking was harmful was 0.98. A negative association between belief in smoking harm and the decision to smoke was shown in regression analysis. This association became more pronounced over the three decades under study. PMID- 25132058 TI - Electrophoretic karyotyping of Hypsizygus marmoreus and evaluation of variation among its basidiospores. AB - The molecular karyotype of Hypsizygus marmoreus was explored by contour-clamped homogeneous electric field gel electrophoresis. Eleven chromosomal bands were separated from the dikaryotic mycelia of H. marmoreus (strain Hm 3-10), and the chromosomes ranged in size from 1.9 to 5.8 Mb. The total genome size of the strain was estimated to be 36.3 Mb. The chromosome numbers were also confirmed by telomere fingerprinting, and 22 telomeric bands were identified. This result suggests that 11 chromosomes exist in Hm 3-10. The marker sequences for each chromosome were determined and were applied to identify each chromosome. Karyotyping and Southern blot analysis revealed that the size of chromosomes in the basidiospores were greatly different from those of parental dikaryon Hm 3-10 cells. PMID- 25132059 TI - Retinoid metabolism in invertebrates: when evolution meets endocrine disruption. AB - Recent genomic and biochemical evidence in invertebrate species pushes back the origin of the retinoid metabolic and signaling modules to the last common ancestor of all bilaterians. However, the evolution of retinoid pathways are far from fully understood. In the majority of non-chordate invertebrate lineages, the ongoing functional characterization of retinoid-related genes (metabolism and signaling pathways), as well as the characterization of the endogenous retinoid content (precursors and active retinoids), is still incomplete. Despite limited, the available data supports the presence of biologically active retinoid pathways in invertebrates. Yet, the mechanisms controlling the spatial and temporal distribution of retinoids as well as their physiological significance share similarities and differences with vertebrates. For instance, retinol storage in the form of retinyl esters, a key feature for the maintenance of retinoid homeostatic balance in vertebrates, was only recently demonstrated in some mollusk species, suggesting that such ability is older than previously anticipated. In contrast, the enzymatic repertoire involved in this process is probably unlike that of vertebrates. The suggested ancestry of active retinoid pathways implies that many more metazoan species might be potential targets for endocrine disrupting chemicals. Here, we review the current knowledge about the occurrence and functionality of retinoid metabolic and signaling pathways in invertebrate lineages, paying special attention to the evolutionary origin of retinoid storage mechanisms. Additionally, we summarize existing information on the endocrine disruption of invertebrate retinoid modules by environmental chemicals. Research priorities in the field are highlighted. PMID- 25132060 TI - A survey of gastro-intestinal parasitic infection in domestic and wild birds in Chittagong and Greater Sylhet, Bangladesh. AB - A survey of gastrointestinal parasitic infection as determined by faecal examination was conducted among domestic and wild birds in Bangladesh. Birds were sampled from households, wet markets and wetlands in Chittagong and Greater Sylhet districts during April 2012 to February 2013. Mist nets were used to catch resident wild and migratory birds. The overall prevalence of parasitic infection ranged among locations from 25 to 55% in indigenous domestic ducks (live bird samples=304), 20% in resident wild birds (environmental faecal samples=40) and 40% in migratory birds (live bird samples=35). The prevalence of parasitic infection was significantly higher in indigenous domestic ducks collected during summer (39%) than winter (22%) (p=0.04). In domestic indigenous ducks and Muscovy ducks, both single and multiple types of parasitic infections were found. However, other domestic birds and wild birds often had a single type of parasitic infection. Ascaridia spp. with an average egg load of 50-900, was commonly detected in faecal samples of domestic and wild birds in this study. Other identified parasites were Capillaria spp. and Heterakis spp. both in domestic and wild birds. Improvement of biosecurity measures for household duck farms through educating and motivating household farmers could help mitigate the effects of parasitic infection on production. PMID- 25132061 TI - Risk factors for occupational brucellosis among veterinary personnel in Turkey. AB - Veterinarians and veterinary technicians are at risk for occupational brucellosis. We described the risk factors of occupational brucellosis among veterinary personnel in Turkey. A multicenter retrospective survey was performed among veterinary personnel who were actively working in the field. Of 712 veterinary personnel, 84 (11.8%) had occupational brucellosis. The median number of years since graduation was 7 (interquartile ranges [IQR], 4-11) years in the occupational brucellosis group, whereas this number was 9 (IQR, 4-16) years in the non-brucellosis group (p<0.001). In multivariable analysis, working in the private sector (odds ratio [OR], 2.8; 95% confidence interval [95% CI], 1.55 5.28, p=0.001), being male (OR, 4.5; 95% CI, 1.05-18.84, p=0.041), number of performed deliveries (OR, 1.01; 95% CI, 1.002-1.02, p=0.014), and injury during Brucella vaccine administration (OR, 5.4; 95% CI, 3.16-9.3, p<0.001) were found to be risk factors for occupational brucellosis. We suggest that all veterinary personnel should be trained on brucellosis and the importance of using personal protective equipment in order to avoid this infection. PMID- 25132063 TI - Similarity between generic and brand-name antihypertensive drugs for primary prevention of cardiovascular disease: evidence from a large population-based study. AB - BACKGROUND: Although generic and earlier brand-name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern. OBJECTIVE: To compare effectiveness of generic and brand-name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes. DESIGN AND SUBJECTS: A population-based, nested case-control study was carried out by including the cohort of 78 520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand-name agents. RESULTS: There was no evidence that patients who started on generics experienced different CV risk than those on brand-name product (OR 0.86; 95% CI 0.63-1.17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand-name agents (OR 1.19; 95% CI 0.86-1.63). Compared with patients who kept initial brand-name therapy, those who experienced brand-to-generic or generic-to-brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1.18 (0.96-1.47), 0.87 (0.63-1.21) and 1.08 (0.80-1.46). CONCLUSIONS: Our findings do not support the notion that brand-name antihypertensive agents are superior to generics for preventing CV outcomes in the real-world clinical practice. PMID- 25132062 TI - Deletion of serine/arginine-rich splicing factor 3 in hepatocytes predisposes to hepatocellular carcinoma in mice. AB - Alterations in RNA splicing are associated with cancer, but it is not clear whether they result from malignant transformation or have a causative role. We show here that hepatocyte-specific deletion of serine/arginine-rich splicing factor 3 (SRSF3) impairs hepatocyte maturation and metabolism in early adult life, and mice develop spontaneous hepatocellular carcinoma (HCC) with aging. Tumor development is preceded by chronic liver disease with progressive steatosis and fibrosis. SRSF3 protects mice against CCl4 -induced fibrosis and carcinogenesis and suppresses inclusion of the profibrogenic EDA exon in fibronectin 1. Loss of SRSF3 increases expression of insulin-like growth factor 2 and the A-isoform of the insulin receptor, allowing aberrant activation of mitogenic signaling, promotes aberrant splicing and expression of epithelial to mesenchymal transition (EMT) genes, and activates Wnt/beta-catenin signaling leading to c-Myc induction. Finally, SRSF3 expression is either decreased or the protein mislocalized in human HCC. CONCLUSION: Our data suggest a potential role for SRSF3 in preventing hepatic carcinogenesis by regulating splicing to suppress fibrosis, mitogenic splicing, and EMT. Thus, these mice may provide an attractive model to discover the pathogenic mechanisms linking aberrant pre-messenger RNA splicing with liver damage, fibrosis, and HCC. PMID- 25132064 TI - Impact of defective interfering particles on virus replication and antiviral host response in cell culture-based influenza vaccine production. AB - During the replication of influenza viruses, defective interfering particles (DIPs) can be generated. These are noninfectious deletion mutants that require coinfection with a wild-type virus but interfere with its helper virus replication. Consequently, coinfected cells mainly produce DIPs. Little is known about how such noninfectious virus particles affect the virus yield of cell culture-based influenza vaccine production. We compared infections of Madin-Darby canine kidney cells with two seed virus preparations of the influenza virus strain A/Puerto Rico/8/34 that contain different amounts of DIPs. A combination of conventional RT-PCR, RT-qPCR, and flow cytometry revealed that DI genomes indeed strongly accumulate in coinfected cells and impede the viral RNA synthesis. Additionally, cells infected at the higher DIP concentration showed a stronger antiviral response characterized by increased interferon-beta expression and apoptosis induction. Furthermore, in the presence of DIPs, a significant fraction of cells did not show any productive accumulation of viral proteins at all. Together, these effects of DIPs significantly reduce the virus yield. Therefore, the accumulation of DIPs should be avoided during influenza vaccine production which can be achieved by quality controls of working seed viruses based on conventional RT-PCR. The strategy for the depletion of DIPs presented here can help to make cell culture-based vaccine production more reliable and robust. PMID- 25132065 TI - Effect of lithium chloride on the production and sialylation of Fc-fusion protein in Chinese hamster ovary cell culture. AB - Lithium chloride (LiCl), which is a specific inhibitor of glycogen synthase kinase-3beta, is known to induce cell cycle arrest at the G2/M phase and to regulate apoptosis. To determine the potential of LiCl as a chemical additive to enhance specific productivity (q p) of recombinant Chinese hamster ovary (rCHO) cells through cell cycle arrest at G2/M phase, rCHO cells producing Fc-fusion protein were cultivated in serum-free media with LiCl concentrations ranging from 0 to 20 mM. The addition of LiCl induced cell cycle arrest at G2/M phase and thereby decreased the specific cell growth rate. However, LiCl increased q p in a dose-dependent manner. The beneficial effect of LiCl on q p outweighed its detrimental effect on MU, resulting in improved maximum Fc-fusion protein concentration (MFPC) at 10 mM LiCl. The q p and MFPC in the bioreactor culture with 10 mM LiCl were 5.0 and 2.1 times higher than those without LiCl, respectively. In addition, the presence of LiCl at 10 mM did not significantly affect either intracellular alpha2,3-ST or extracellular sialidase activity. LiCl also inhibited apoptosis of cells in the decline phase of growth by increasing Bcl-2 expression. Taken together, the results obtained in this study demonstrate the potential of LiCl as a q p-enhancing additive in CHO cell culture for improved recombinant protein production. PMID- 25132066 TI - Patients' perspectives on the role of their general practitioner after receiving an advanced cancer diagnosis. AB - The aim of this study was to explore patients' perspectives on the role of their general practitioner (GP) after an advanced cancer diagnosis. A qualitative research approach was used. Semi-structured interviews were conducted and data were analysed using a constant comparative methodology. Participants were eligible if they were diagnosed with advanced cancer and referred for palliative radiotherapy. Data saturation was achieved after 21 interviews. Key themes included (1) obtaining diagnosis and referral for advanced cancer treatment; (2) preference for specialist oncology care; (3) a preference for GP to act as an advocate; and (4) obtaining ongoing routine care from their GP. GP involvement in the patients' management was dependent on: time since diagnosis, GP's involvement in diagnosis and referral, doctor/patient relationship, additional chronic conditions requiring management, frequency of seeing oncologist and specialist recommendation to involve GP. Patients want GPs to have varying levels of involvement following an advanced cancer diagnosis. Not all communication between GPs and patients was positive suggesting communication skills training may be a priority. Patients wished to maintain continunity of care for their non-cancer related issues and healthcare of their family members. Future research needs to focus on working with GPs to increase their role in the management of advanced cancer. PMID- 25132067 TI - RNA structural analysis by evolving SHAPE chemistry. AB - RNA is central to the flow of biological information. From transcription to splicing, RNA localization, translation, and decay, RNA is intimately involved in regulating every step of the gene expression program, and is thus essential for health and understanding disease. RNA has the unique ability to base-pair with itself and other nucleic acids to form complex structures. Hence the information content in RNA is not simply its linear sequence of bases, but is also encoded in complex folding of RNA molecules. A general chemical functionality that all RNAs have is a 2'-hydroxyl group in the ribose ring, and the reactivity of the 2' hydroxyl in RNA is gated by local nucleotide flexibility. In other words, the 2' hydroxyl is reactive at single-stranded and conformationally flexible positions but is unreactive at nucleotides constrained by base-pairing. Recent efforts have been focused on developing reagents that modify RNA as a function of RNA 2' hydroxyl group reactivity. Such RNA structure probing techniques can be read out by primer extension in experiments termed RNA SHAPE (selective 2'- hydroxyl acylation and primer extension). Herein, we describe the efforts devoted to the design and utilization of SHAPE probes for characterizing RNA structure. We also describe current technological advances that are being applied to utilize SHAPE chemistry with deep sequencing to probe many RNAs in parallel. The merging of chemistry with genomics is sure to open the door to genome-wide exploration of RNA structure and function. PMID- 25132069 TI - Decreased lipases and fatty acid and glycerol transporter could explain reduced fat in diabetic morbidly obese. AB - OBJECTIVE: The possible differences were investigated in 32 morbidly obese patients depending on whether they were "healthy" or had dyslipidemia and/or type 2 diabetes. METHODS: Lipid metabolism and insulin resistance were analyzed in subcutaneous (SAT) and visceral adipose tissue (VAT) before and during 6 and 12 months after Roux-en-Y gastric bypass. RESULTS: Significant differences have been found in lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities in SAT from the different obese group versus normal weight (control) but not between them. The reduced lipase activities in VAT were 43 and 19% smaller (22 and 4% smaller, respectively, vs. control) than the "healthy" obese group for LPL and HSL, respectively, and were accompanied with a reduced expression of these lipases, as well as decreased expression of FAT/CD36, FABP4, and AQ7 in that tissue. In addition, the expression of the other genes measured showed a downregulation not only versus the "healthy" obese but also versus the normal weight group. CONCLUSIONS: Being obese is not "healthy," but it is even less so if morbidly obese patients with diabetes and dyslipidemia were considered. The reduced fat accumulation in these patients may be attributed to the decrease of the expression and activity of the lipases of their adipose tissue. PMID- 25132068 TI - The scientific quest for lasting youth: prospects for curing aging. AB - People have always sought eternal life and everlasting youth. Recent technological breakthroughs and our growing understanding of aging have given strength to the idea that a cure for human aging can eventually be developed. As such, it is crucial to debate the long-term goals and potential impact of the field. Here, I discuss the scientific prospect of eradicating human aging. I argue that curing aging is scientifically possible and not even the most challenging enterprise in the biosciences. Developing the means to abolish aging is also an ethical endeavor because the goal of biomedical research is to allow people to be as healthy as possible for as long as possible. There is no evidence, however, that we are near to developing the technologies permitting radical life extension. One major difficulty in aging research is the time and costs it takes to do experiments and test interventions. I argue that unraveling the functioning of the genome and developing predictive computer models of human biology and disease are essential to increase the accuracy of medical interventions, including in the context of life extension, and exponential growth in informatics and genomics capacity might lead to rapid progress. Nonetheless, developing the tools for significantly modifying human biology is crucial to intervening in a complex process like aging. Yet in spite of advances in areas like regenerative medicine and gene therapy, the development of clinical applications has been slow and this remains a key hurdle for achieving radical life extension in the foreseeable future. PMID- 25132071 TI - Catalytic activity of an encaged Verkade's superbase in a base-catalyzed Diels Alder reaction. AB - Organocatalysis in a confined space has been performed through encapsulation of a proazaphosphatrane superbase in a hemicryptophane host. The resulting catalyst displays good to high catalytic activity in the base-catalyzed Diels-Alder reactions investigated. A comparison with the model superbase, which lacks a cavity, shows much higher diastereomeric excess with the encaged proazaphosphatrane for the reaction of 3-hydroxy-2-pyrone with N-methylmaleimide. The use of an encaged superbase as organocatalyst is unprecedented and highlights how the confinement may impact the stereoselectivity. PMID- 25132070 TI - Combining family- and population-based imputation data for association analysis of rare and common variants in large pedigrees. AB - In the last two decades, complex traits have become the main focus of genetic studies. The hypothesis that both rare and common variants are associated with complex traits is increasingly being discussed. Family-based association studies using relatively large pedigrees are suitable for both rare and common variant identification. Because of the high cost of sequencing technologies, imputation methods are important for increasing the amount of information at low cost. A recent family-based imputation method, Genotype Imputation Given Inheritance (GIGI), is able to handle large pedigrees and accurately impute rare variants, but does less well for common variants where population-based methods perform better. Here, we propose a flexible approach to combine imputation data from both family- and population-based methods. We also extend the Sequence Kernel Association Test for Rare and Common variants (SKAT-RC), originally proposed for data from unrelated subjects, to family data in order to make use of such imputed data. We call this extension "famSKAT-RC." We compare the performance of famSKAT RC and several other existing burden and kernel association tests. In simulated pedigree sequence data, our results show an increase of imputation accuracy from use of our combining approach. Also, they show an increase of power of the association tests with this approach over the use of either family- or population based imputation methods alone, in the context of rare and common variants. Moreover, our results show better performance of famSKAT-RC compared to the other considered tests, in most scenarios investigated here. PMID- 25132074 TI - Improved hydroxyurea effect with the use of text messaging in children with sickle cell anemia. AB - BACKGROUND: In children with sickle cell anemia (SCA), hydroxyurea reduces morbidity, but adherence is frequently suboptimal. Because most families of children with SCA have access to cellular telephone services, we assessed the impact of text messaged reminders as a tool to improve adherence to hydroxyurea. PROCEDURE: All patients <19 years of age with HbSS or HbSbeta(0) thalassemia who were treated with hydroxyurea at a maximal tolerated dosage (MTD) at St. Jude Children's Research Hospital Comprehensive Pediatric Sickle Cell Program and who received automated text message reminders (SIMON(r)) were retrospectively identified. Laboratory parameters, hospitalizations, and medication possession ratios (MPR) prior to and after initiation of SIMON(r) were compared to assess the impact of SIMON(r). RESULTS: Of the 97.3% of families with access to a cell phone, 91% elected to receive text message reminders. Among 55 children receiving hydroxyurea at MTD, laboratory parameters reflected waning medication compliance during the 12 months prior to SIMON(r). Following initiation of SIMON(r), children had higher mean corpuscular volumes, hemoglobin levels and fetal hemoglobin percentages and lower absolute reticulocyte counts and bilirubin levels, suggesting improved medication adherence. Hospitalizations were uncommon before and after SIMON(r), and medication possession ratios (MPRs) were high before and after SIMON(r), neither was significantly changed. CONCLUSIONS: SIMON(r) was feasible and improved hematologic parameters in children with SCA receiving hydroxyurea at a MTD. Future work will include extension of this technology to children with other chronic medical conditions who require daily use of medication. PMID- 25132073 TI - Transforming growth factor-beta1 mediates psoriasis-like lesions via a Smad3 dependent mechanism in mice. AB - Transforming growth factor (TGF)-beta1 signals through downstream Smad-dependent and -independent pathways to exert its biological actions. It has been reported that overexpression of TGF-beta1 results in the development of psoriasis-like lesions in a mouse model of K5.TGF-beta(WT) transgenic mice. However, the signalling mechanisms by which TGF-beta1 mediates the development of psoriasis like lesions remain unknown. The aim of the present study was to investigate the hypothesis that TGF-beta1 mediates the development of psoriasis-like lesions via a Smad3-dependent mechanism. This was tested in a mouse model of K5.TGF-beta(WT) transgenic mice by blocking TGF-beta signalling with a specific Smad3 inhibitor. Topical treatment with a Smad3 inhibitor markedly blocked TGF-beta/Smad3 signalling and progressive psoriasis-like lesions in K5.TGF-beta(WT) transgenic mice, as evidenced by decreased skin severity scores, double skin fold thickness (DSFT) scores, infiltration of CD3(+) T cells and F4/80(+) macrophages and the degree of fibrosis in the dermis. This was associated with a marked reduction in TGF-beta1, interleukin (IL)-6, IL-23 and IL-17A both locally in skin plaque lesions and systemically in the plasma, resulting in inhibition of both the T helper (Th) 17 cell transcription factor RORgammat and accumulation of CD4(+) IL 17A(+) cells within the skin plaque lesions. In conclusion, TGF-beta1 mediates the development of psoriasis-like lesions via a Smad3-dependent, Th17-mediated mechanism. Targeting TGF-beta/Smad3 signalling with a Smad3 inhibitor may represent a novel and effective therapy for psoriasis. PMID- 25132072 TI - Maternal periconceptional alcohol consumption and congenital limb deficiencies. AB - BACKGROUND: Women of childbearing age report high rates of alcohol consumption, which may result in alcohol exposure during early pregnancy. Epidemiological research on congenital limb deficiencies (LDs) and periconceptional exposure to alcohol is inconclusive. METHODS: Data from the National Birth Defects Prevention Study (NBDPS) were examined for associations between LDs and patterns of maternal periconceptional (1 month before conception through the first trimester) alcohol consumption among LD case (n = 906) and unaffected control (n = 8352) pregnancies with expected delivery dates from 10/1997 through 12/2007. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated from unconditional logistic regression analysis for all LDs combined, specific LD subtypes (preaxial/terminal transverse), and LD anatomic groups (upper/lower limbs); interactions with folic acid (FA) supplementation were tested. RESULTS: When compared with nondrinkers, inverse associations were found between all LDs combined, preaxial, and upper LDs and any reported periconceptional alcohol consumption (aORs ranged from 0.56 0.83), drinking without binging (aORs: 0.53-0.75), and binge drinking (>=4 drinks/occasion) (aORs: 0.64-0.94); however, none of the binge drinking aORs were statistically significant. Stratification by alcohol type showed inverse associations between all LDs combined, preaxial, transverse, and upper and lower LDs for drinking without binging of wine only (aORs: 0.39-0.67) and between all LDs combined and upper LDs for drinking without binging of combinations of alcohol (aORs: 0.63-0.87). FA did not modify observed associations. CONCLUSION: Maternal periconceptional alcohol consumption did not emerge as a teratogen for selected LDs in the NBDPS. Future studies should evaluate additional rare LDs among more highly exposed populations. PMID- 25132075 TI - Molecular analysis of the interspousal transmission of hepatitis B virus in two Japanese patients who acquired fulminant hepatitis B after 50 and 49 years of marriage. AB - A 71-year-old (C1I) and 69-year-old (C2I) Japanese female contracted fulminant hepatitis B after 50 and 49 years of marriage, respectively. Both index cases exhibited high levels of anti-HBc IgM antibodies (24.2 and 31.5 S/CO, respectively), suggestive of acute hepatitis B virus (HBV) infection, although they had no discernible risk factors for HBV infection, except for chronically HBV-infected spouses with detectable HBV DNA (3.3 log copies/ml [C1S: 72-year old] and 7.2 log copies/ml [C2S: 71-year-old]). The HBV genotype/subgenotype was identical in each couple (B/B1 or C/C2). The HBV isolates from the index cases and spouses shared a nucleotide sequence identity of 99.5% and 99.7%, respectively, over the entire genome, and these four isolates had the highest nucleotide sequence identity of only 97% to HBV isolates deposited in DNA databases. Phylogenetic trees confirmed a close relationship of the HBV isolates between C1I and C1S and between C2I and C2S, supported by a high bootstrap value of 100% within each couple, indicating the transfer of HBV infection between spouses. These four isolates shared a precore mutation of G1896A known to be associated with fulminant hepatitis B. Although the history of sexual contact within a reasonable incubation period was obscure for one stable, monogamous couple (C1I and C1S), the other couple had a monogamous sexual relationship within six months prior to disease onset. This study indicates that two elderly Japanese patients with fulminant hepatitis B acquired HBV infection via interspousal (most likely sexual) transmission during long-lasting marriages. PMID- 25132076 TI - Retrospective analysis of treatment outcomes following reirradiation in locoregionally recurrent head and neck cancer patients: A single institutional study. AB - AIM: To present a retrospective analysis of treatment outcomes following reirradiation in locoregionally recurrent head and neck cancer patients at our institute. METHODS: Thirty-one patients of head and neck cancer who presented with a locoregional recurrence from April 2007 to April 2012 underwent salvage reirradiation. Median dose of first-time radiation was 70 Gy. Median duration of gap between the first and second course of radiation was 45.6 months. The median dose of reirradiation was 60 Gy. Conformal radiotherapy technique in the form of intensity modulated radiotherapy was used in 60% (17) of patients. Fourteen patients received concurrent chemotherapy or immunotherapy. RESULTS: After a median follow-up of 20.6 months, 12 patients were alive with no evidence of disease. The 3-year disease-free survival and overall survival were 28.7 and 48.5%, respectively. Acute and late toxicities were reported in 29 and 61% of patients, respectively. Severe grade 3 and 4 late complications were observed in nine patients but none of them led to mortality. CONCLUSION: Reirradiation appears to be both feasible and well tolerated in patients treated with previous radiotherapy for recurrent and second primary head and neck cancer. Careful case selection for reirradiation based on patient's performance status and tumor characteristics is essential. PMID- 25132077 TI - ARFI elastography as a complementary diagnostic method for mammary neoplasia in female dogs - preliminary results. AB - OBJECTIVES: To evaluate the applicability of acoustic radiation force impulse elastography as a complementary method in diagnosing mammary neoplasia in dogs. METHODS: Mammary tumours from 50 female dogs were evaluated and divided into two groups: G1 (benign tissue) and G2 (malignant tumours). The nodules were assessed by B-Mode ultrasonography, qualitative and quantitative acoustic radiation force impulse elastography and histopathology. RESULTS: B-Mode ultrasound examination was ineffective at separating the tumours into the two groups. Likewise, there was no correlation between the grayscale images of the mammary tissue by qualitative elastography. A difference was found in the deformity of the mammary masses between the malignant and benign groups (P = 0 . 002). Using quantitative elastography, the mean values of shear velocity were 3 . 33 m/s for malignant tumours and 1 . 28 m/s for benign tissue (P < 0 . 0001). CLINICAL SIGNIFICANCE: The use of acoustic radiation force impulse elastography may help to differentiate between malignant and benign mammary neoplasms. PMID- 25132079 TI - Regulation of mitochondrial apoptosis by Pin1 in cancer and neurodegeneration. AB - Mitochondria are sensitive and efficient organelles that regulate essential biological processes including: energy metabolism, decoding and transduction of intracellular signals, and balance between cell death and survival. Of note, dysfunctions in mitochondrial physiology are a general hallmark of cancer cells, leading to transformation-related features such as altered cellular metabolism, survival under stress conditions and reduced apoptotic response to chemotherapy. Mitochondrial apoptosis is a finely regulated process that derives from activation of multiple signaling networks. A crucial biochemical requirement for transducing pro-apoptotic stimuli is represented by kinase-dependent phosphorylation cascades. In this context a pivotal role is played by the prolyl isomerase Pin1, which translates Ser/Thr-Pro phosphorylation into conformational changes able to modify the activities of its substrates. In this review we will discuss the impact of Pin1 in regulating various aspects of apoptosis in different biological contexts with particular emphasis on cancer and neurodegenerative diseases. PMID- 25132078 TI - Efficacy of catheter ablation for persistent atrial fibrillation: a systematic review and meta-analysis of evidence from randomized and nonrandomized controlled trials. AB - BACKGROUND: Catheter ablation (CA) is commonly performed for persistent atrial fibrillation, but few high-quality randomized controlled trials (RCTs) exist, leading to funding restrictions being proposed in several countries. We performed a random-effects meta-analysis of RCTs and non-RCTs to assess the efficacy of CA for persistent atrial fibrillation. METHODS AND RESULTS: We systematically searched PubMed, EMBASE, CENTRAL, OpenGrey, and clinicaltrials.gov for RCTs and non-RCTs reporting clinical outcomes after CA for persistent atrial fibrillation. Forty-six eligible studies were identified containing 3819 patients. After a single procedure, CA significantly reduced the risk of recurrent atrial fibrillation compared with medical therapy (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.20-0.53; P<0.001). Outcomes were better if the pulmonary veins were encircled (OR, 0.26; 95% CI, 0.09-0.74; P=0.01), and electrical isolation reduced AF recurrence compared with purely anatomic encirclement (OR, 0.33; 95% CI, 0.13-0.86; P=0.02). Linear ablation within the left atrium (OR, 0.22; 95% CI, 0.10-0.49; P<0.001), but not complex fractionated atrial electrogram ablation (OR, 0.64; 95% CI, 0.35-1.18; P=0.15), significantly reduced AF recurrence. Results were not improved by performing more extensive linear lesion sets (OR, 0.77; 95% CI, 0.41-1.43; P=0.40) or from biatrial ablation (OR, 0.62; 95% CI, 0.31-1.24; P=0.17). Where data were available, the relative benefits seen held true both after a single or multiple procedure(s). Sensitivity analyses showed that inclusion of non-RCTs increased statistical power without biasing the calculated effect sizes. CONCLUSIONS: For patients with persistent atrial fibrillation, CA achieves significantly greater freedom from recurrent atrial fibrillation compared with medical therapy. The most efficacious strategy is likely to combine isolation of the pulmonary veins with limited linear ablation within the left atrium. PMID- 25132080 TI - Mitochondrial macro-haplogroup JT may play a protective role in ovarian ageing. AB - This study of 200 Caucasian women shows that the distribution of the mtDNA macro haplogroups in patients with diminished ovarian reserve (DOR) differed significantly from that of patients with normal ovarian reserve (NOR) (p=0.02). The JT macro-haplogroup was significantly under-represented in DOR patients compared with NOR patients (p=0.006) and compared with the estimated frequency of 18.8% in the general French population (p=0.0012). Our findings suggest that the risk of a prematurely depleted ovarian reserve would be three times lower for patients carrying the JT macro-haplogroup than for patients with any of the other mtDNA haplogroups (odds ratio: 0.3; 95% CI: 0.13-0.74). If these preliminary results are confirmed in larger independent studies, they should lead to the better management of infertility. PMID- 25132081 TI - Efficacy of liposome-encapsulated hemoglobin in a rat model of cerebral ischemia. AB - Use of liposome-encapsulated hemoglobin (LEH) for oxygen delivery in the treatment of cerebral ischemia has been studied previously and its expected benefits confirmed. However, the relationship between the timing of administration and the efficacy of LEH in cerebral ischemia has not been studied in detail. We therefore investigated the therapeutic time window of LEH by using a rat model of cerebral ischemia, as well as evaluating the contribution of oxygen delivery to the efficacy of LEH. Dose-dependent effects and the therapeutic time window of LEH were studied using models of transient and permanent middle cerebral artery occlusion (MCAO), respectively, in SD rats. LEH was intravenously administered at 0.5 h after the onset of ischemia in the transient MCAO model and at 0.5, 2, 4, or 6 h in the permanent MCAO model. Efficacy of LEH treatment was evaluated using the infarct volume, which was examined with 2,3,5-triphenyltetrazolium chloride staining and estimated by integrating the unstained areas in serial sections of cerebral tissue. Effects of oxygen delivery by LEH were examined immunohistochemically with pimonidazole to stain for areas of low oxygen tension in the tissue. LEH treatment dose dependently reduced the cerebral infarct volume, which was especially significant in the cortical region at doses of over 60 mg hemoglobin (Hb)/kg. In rats with permanent MCAO, LEH administration at a dose of 300 mg Hb/kg at 0.5 h and 2 h after the onset of cerebral ischemia significantly reduced cerebral infarct volume. Furthermore, immunohistochemical staining with pimonidazole showed that the areas of cerebral tissue that were hypoxic and had abnormal histological structure were reduced after LEH treatment. These results indicated that LEH is efficacious in the treatment of cerebral infarction secondary to MCAO and that oxygen delivery to ischemic cerebral tissues by LEH administered early after the onset of cerebral ischemia contributes to this effect. PMID- 25132082 TI - L-Arabinose binding, isomerization, and epimerization by D-xylose isomerase: X ray/neutron crystallographic and molecular simulation study. AB - D-xylose isomerase (XI) is capable of sugar isomerization and slow conversion of some monosaccharides into their C2-epimers. We present X-ray and neutron crystallographic studies to locate H and D atoms during the respective isomerization and epimerization of L-arabinose to L-ribulose and L-ribose, respectively. Neutron structures in complex with cyclic and linear L-arabinose have demonstrated that the mechanism of ring-opening is the same as for the reaction with D-xylose. Structural evidence and QM/MM calculations show that in the reactive Michaelis complex L-arabinose is distorted to the high-energy (5)S1 conformation; this may explain the apparent high KM for this sugar. MD-FEP simulations indicate that amino acid substitutions in a hydrophobic pocket near C5 of L-arabinose can enhance sugar binding. L-ribulose and L-ribose were found in furanose forms when bound to XI. We propose that these complexes containing Ni(2+) cofactors are Michaelis-like and the isomerization between these two sugars proceeds via a cis-ene-diol mechanism. PMID- 25132083 TI - HIV-1 envelope protein gp41: an NMR study of dodecyl phosphocholine embedded gp41 reveals a dynamic prefusion intermediate conformation. AB - Human immunodeficiency viral (HIV-1) fusion is mediated by the viral envelope gp120/gp41 complex (ENVelope glycoprotein). After gp120 shedding, gp41 is exposed and elicits membrane fusion via a cascade of conformational changes. In contrast to prefusion and postfusion conformation, little is known about any intermediate conformation. We report on a solution NMR investigation of homotrimeric HIV-1 gp41(27-194), comprising the transmembrane region and reconstituted in dodecyl phosphocholine (DPC) micelles. The protein is mainly alpha-helical, but experiences internal dynamics on the nanosecond and micro to millisecond time scale and transient alpha-helical behavior for certain residues in the N-terminal heptad repeat (NHR). Strong lipid interactions are observed, in particular for C terminal residues of the NHR and imunodominant loop region connecting NHR and C terminal heptad repeat (CHR). Our data indicate an extended conformation with features anticipated for a prefusion intermediate, presumably in exchange with a lowly populated postfusion six-helical bundle conformation. PMID- 25132086 TI - Synthesis, surface properties and antimicrobial activity of some germanium nonionic surfactants. AB - Esterification reaction between different fatty acid namely; lauric, stearic, oleic and linoleic acids and polyethylene glycol-400 were performed. The produced polyethylene glycol ester were reacted with p-amine benzoic acid followed by condensation reaction with germanium dioxide in presence of sodium carbonate to form desired germinate surfactants. The chemical structures of the synthesized surfactants were determined using different spectra tools. The surface parameter including: the critical micelle concentration (CMC), effectiveness (pi(cmc)), efficiency (Pc20), maximum surface excess (Gamma(max)) and minimum surface area (A(min)), were calculated from the surface tension measurements. The synthesized surfactants showed higher surface activity. The thermodynamic parameters showed that adsorption and micellization processes are spontaneous. It is clear that the synthesized nonionic surfactants showed their tendency towards adsorption at the interfaces and also micellization in the bulk of their solutions. The synthesized surfactants were tested against different strain of bacteria using inhibition zone diameters. The synthesized surfactants showed good antimicrobial activities against the tested microorganisms including Gram positive, Gram negative as well as fungi. The promising inhibition efficiency of these compounds against the sulfate reducing bacteria facilitates them to be applicable as new categories of sulfate reducing bacteria biocides. PMID- 25132085 TI - Crystal structures of designed armadillo repeat proteins: implications of construct design and crystallization conditions on overall structure. AB - Designed armadillo repeat proteins (dArmRP) are promising modular proteins for the engineering of binding molecules that recognize extended polypeptide chains. We determined the structure of a dArmRP containing five internal repeats and 3rd generation capping repeats in three different states by X-ray crystallography: without N-terminal His6 -tag and in the presence of calcium (YM5 A/Ca(2+) ), without N-terminal His6 -tag and in the absence of calcium (YM5 A), and with N terminal His6 -tag and in the presence of calcium (His-YM5 A/Ca(2+)). All structures show different quaternary structures and superhelical parameters. His YM5 A/Ca(2+) forms a crystallographic dimer, which is bridged by the His6 -tag, YM5 A/Ca(2+) forms a domain-swapped tetramer, and only in the absence of calcium and the His6 -tag, YM5 A forms a monomer. The changes of superhelical parameters are a consequence of calcium binding, because calcium ions interact with negatively charged residues, which can also participate in the modulation of helix dipole moments between adjacent repeats. These observations are important for further optimizations of dArmRPs and provide a general illustration of how construct design and crystallization conditions can influence the exact structure of the investigated protein. PMID- 25132084 TI - Structural mapping of divergent regions in the type 1 ryanodine receptor using fluorescence resonance energy transfer. AB - Ryanodine receptors (RyRs) release Ca(2+) to initiate striated muscle contraction. Three highly divergent regions (DRs) in the RyR protein sequence (DR1, DR2, and DR3) may confer isoform-specific functional properties to the RyRs. We used cell-based fluorescence resonance energy transfer (FRET) measurements to localize these DRs to the cryoelectron microscopic (cryo-EM) map of the skeletal muscle RyR isoform (RyR1). FRET donors were targeted to RyR1 using five different FKBP12.6 variants labeled with Alexa Fluor 488. FRET was then measured to the FRET acceptors, Cy3NTA or Cy5NTA, targeted to decahistidine tags introduced within the DRs. DR2 and DR3 were localized to separate positions within the "clamp" region of the RyR1 cryo-EM map, which is presumed to interface with Cav1.1. DR1 was localized to the "handle" region, near the regulatory calmodulin-binding site on the RyR. These localizations provide insights into the roles of DRs in RyR allosteric regulation during excitation contraction coupling. PMID- 25132087 TI - Influence of extraction techniques on physical-chemical characteristics and volatile compounds of extra virgin olive oil. AB - The purpose of this study was to investigate three types of extraction methods of extra virgin olive oil (EVOO) from the same cultivar (Ortice olive cultivar): traditional or pressing (T) system, decanter centrifugation (DC) system and a patented horizontal axis decanter centrifugation (HADC) system. Oil samples were subjected to chemical analyses: free acidity, peroxide value, ultraviolet light absorption K232 and K270, total polyphenols, antioxidant capacity, volatile compounds and olfactory characteristics by electronic nose. The two centrifugation systems showed better free acidity and peroxides value but total polyphenol content was particularly high in extra virgin olive oil produced by patented HADC system. Same volatile substances that positively characterize the oil aroma were found in higher amount in the two centrifugation systems, although some differences have been detected between DC and HADC system, other were found in higher amount in extra virgin olive oil produced by T system. The electronic nose analysis confirmed these results, principal component analysis (PCA) and correlation matrix showed the major differences between EVOO produced by T and HADC system. Taken together the results showed that DC and HADC systems produce EVOO with better characteristics than T system and patented HADC is the best extraction system. PMID- 25132088 TI - Hydrodistillation extraction time effect on essential oil yield, composition, and bioactivity of coriander oil. AB - Coriander (Coriandrum sativum L.) is a major essential oil crop grown throughout the world. Coriander essential oil is extracted from coriander fruits via hydrodistillation, with the industry using 180-240 min of distillation time (DT), but the optimum DT for maximizing essential oil yield, composition of constituents, and antioxidant activities are not known. This research was conducted to determine the effect of DT on coriander oil yield, composition, and bioactivity. The results show that essential oil yield at the shorter DT was low and generally increased with increasing DT with the maximum yields achieved at DT between 40 and 160 min. The concentrations of the low-boiling point essential oil constituents: alpha-pinene, camphene, beta-pinene, myrcene, para-cymene, limonene, and gamma-terpinene were higher at shorter DT (< 2.5 min) and decreased with increasing DT; but the trend reversed for the high-boiling point constituents: geraniol and geranyl-acetate. The concentration of the major essential oil constituent, linalool, was 51% at DT 1.15 min, and increased steadily to 68% with increasing DT. In conclusion, 40 min DT is sufficient to maximize yield of essential oil; and different DT can be used to obtain essential oil with differential composition. Its antioxidant capacity was affected by the DT, with 20 and 240 min DT showing higher antioxidant activity. Comparisons of coriander essential oil composition must consider the length of the DT. PMID- 25132089 TI - Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC). AB - OBJECTIVES: We previously reported inferior outcomes for locally-advanced head and neck squamous cell carcinoma (LAHNSCC) patients treated with concurrent cetuximab vs. high-dose cisplatin with intensity-modulated radiation therapy (IMRT). Prior to FDA approval of cetuximab for LAHNSCC, non-cisplatin eligible patients at our institution received 5-fluorouracil (5FU)/carboplatin. We sought to compare concurrent cetuximab vs. 5FU/carboplatin vs. high-dose cisplatin with IMRT for LAHNSCC. MATERIALS AND METHODS: Retrospective review was performed for LAHNSCC patients treated at Memorial Sloan-Kettering Cancer Center from 11/02 to 04/08 with concurrent cetuximab (n=49), 5FU/carboplatin (n=52), or cisplatin (n=259) and IMRT. Overall survival (OS), locoregional failure (LRF), distant metastasis-free survival, and late toxicity were analyzed using univariate and multivariate analyses. OS analysis was confirmed by propensity score adjustment. RESULTS: Treatment groups were similar with regard to primary tumor site, overall stage, and alcohol and tobacco history. Cetuximab and 5FU/carboplatin patients were older, with lower performance status, more comorbidities, higher T classification, and worse renal function. On multivariate analysis, compared with cisplatin and 5FU/carboplatin, cetuximab was associated with inferior 4-year OS (86.9% vs. 70.2% vs. 40.9%; P<.0001) and 4-year LRF (6.3% vs. 9.7% vs. 40.2%; P<.0001). Late toxicity was highest with 5FU/carboplatin (25.0%) vs. cisplatin (8.0%) vs. cetuximab (7.7%). CONCLUSIONS: Although 5FU/carboplatin patients were sicker and experienced greater toxicity than cisplatin patients, no significant difference was found in all endpoints. In contrast, despite similar pretreatment characteristics, outcomes for cetuximab vs. 5FU/carboplatin were significantly worse. We feel that caution should be used with routine use of cetuximab in the management of LAHNSCC. PMID- 25132090 TI - Association between oral leukoplakia and upper gastrointestinal cancers: a 28 year follow-up study in the Linxian General Population Trial. AB - BACKGROUND: Oral leukoplakia is a precancerous disorder that is common among residents in Linxian. However, the associations between oral leukoplakia and upper gastrointestinal cancers have not been reported. We investigated the relationships between oral leukoplakia and upper gastrointestinal cancers in the Linxian General Population Trial cohort. METHODS: The Linxian General Population Trial cohort, with 29,584 healthy adults enrolled in 1985 and followed through the end of 2012. With collected baseline data, hazard ratios (HR) and 95% confidence intervals (95% CI) for developing upper gastrointestinal cancers were estimated using Cox proportional hazard models. RESULTS: During 28 years of follow-up, we confirmed a total of 2924 incident esophageal squamous cell carcinoma (ESCC) cases, 1644 gastric cardia cancers and 590 gastric non-cardia cancers. Overall, participants with oral leukoplakia had significantly higher risk of developing ESCC (HR=1.18, 95% CI: 1.08, 1.29). Among individuals ?52 years old at baseline, oral leukoplakia was associated with elevated risk of ESCC (HR=1.31, 95%CI: 1.15, 1.49). No significant associations were observed for gastric cardia or non-cardia cancers in either all subjects or subgroups. CONCLUSIONS: Oral leukoplakia was associated with increased risk of ESCC, particularly in younger population. Future studies are needed to confirm these findings. PMID- 25132092 TI - Rootstock-to-scion transfer of transgene-derived small interfering RNAs and their effect on virus resistance in nontransgenic sweet cherry. AB - Small interfering RNAs (siRNAs) are silencing signals in plants. Virus-resistant transgenic rootstocks developed through siRNA-mediated gene silencing may enhance virus resistance of nontransgenic scions via siRNAs transported from the transgenic rootstocks. However, convincing evidence of rootstock-to-scion movement of siRNAs of exogenous genes in woody plants is still lacking. To determine whether exogenous siRNAs can be transferred, nontransgenic sweet cherry (scions) was grafted on transgenic cherry rootstocks (TRs), which was transformed with an RNA interference (RNAi) vector expressing short hairpin RNAs of the genomic RNA3 of Prunus necrotic ringspot virus (PNRSV-hpRNA). Small RNA sequencing was conducted using bud tissues of TRs and those of grafted (rootstock/scion) trees, locating at about 1.2 m above the graft unions. Comparison of the siRNA profiles revealed that the PNRSV-hpRNA was efficient in producing siRNAs and eliminating PNRSV in the TRs. Furthermore, our study confirmed, for the first time, the long-distance (1.2 m) transfer of PNRSV-hpRNA derived siRNAs from the transgenic rootstock to the nontransgenic scion in woody plants. Inoculation of nontransgenic scions with PNRSV revealed that the transferred siRNAs enhanced PNRSV resistance of the scions grafted on the TRs. Collectively, these findings provide the foundation for 'using transgenic rootstocks to produce products of nontransgenic scions in fruit trees'. PMID- 25132091 TI - Inhibition of H3K4me2 Demethylation Protects Auditory Hair Cells from Neomycin Induced Apoptosis. AB - Aminoglycoside-induced hair cell loss is a major cause of hearing impairment in children and deserves more attention in medical research. Epigenetic mechanisms have been shown to protect hair cells from ototoxic drugs. In this study, we focused on the role of dimethylated histone H3K4 (H3K4me2) in hair cell survival. To investigate the effects of lysine-specific demethylase 1 (LSD1)--the histone demethylase primarily responsible for demethylating H3K4me2--on neomycin-induced hair cell loss, isolated cochleae were pretreated with LSD1 inhibitors followed by neomycin exposure. There was a severe loss of hair cells in the organ of Corti after neomycin exposure, and inhibition of LSD1 significantly protected against neomycin-induced hair cell loss. H3K4me2 expression in the nuclei of hair cells decreased after exposure to neomycin, and blocking the decreased expression of H3K4me2 with LSD1 inhibitors prevented hair cell loss. Local delivery of these inhibitors in vivo also protected hair cells from neomycin-induced ototoxicity and maintained the hearing threshold in mice as determined by auditory brain stem response. This inhibition of neomycin-induced apoptosis occurs via reduced caspase-3 activation. Together, our findings demonstrate the protective role for H3K4me2 against neomycin-induced hair cell loss and hearing loss. PMID- 25132093 TI - Positive effects of melatonin treatment on the reproductive performance of young border leicester rams mated to merino ewes in spring: preliminary observations. AB - Poor reproductive performance of Merino ewe flocks when mated to Border Leicester rams during spring may be due to seasonality of the Border Leicester breed. Two approaches were taken to test this assumption. Six young (12 months old) or six mixed-age (12, 24 and >=36 months old) Border Leicester rams were either treated or not treated with melatonin implants (2 * 2 design) 6 weeks before the four groups of rams were each put with approximately 300 Merino ewes for an 8-week mating period. Implants were inserted in early September (experiment 1). The second approach was to yard or not yard ewes and mixed-age rams on several occasions during the first 3 weeks of the mating period (experiment 2). Pregnancy rate and twinning percentage were assessed by ultrasonography. In experiment 1, melatonin treatment in young rams increased (p < 0.001) pregnancy rate from 5.0% to 92.6%, but mixed-age rams did not respond (90.7% vs 89.5% for melatonin and non-melatonin treatments, respectively). Twinning rate was similar (p > 0.05) for ewes mated to either melatonin or non-melatonin-treated young rams (36.8% vs 40.0%, respectively), whereas melatonin significantly improved (p < 0.05) twinning rate in those ewes mated to mixed-age rams (49.1% vs 36.1%). After 6 weeks of melatonin treatment, scrotal circumference was greater (p < 0.05) in both young and mixed-aged rams than in untreated counterparts. In experiment 2, yarding of ewes and rams overnight on several occasions early in the mating period reduced (p < 0.001) pregnancy rate compared with non-yarded counterparts (89.5% vs 65.5%). Twinning rate was not affected (37.7% vs 36.1%, respectively). In summary, melatonin treatment of Border Leicester rams significantly improved flock reproductive performance in spring due to improved pregnancy rates with young rams and improved litter size with mixed-age rams. PMID- 25132094 TI - Mucosal immunology: killing time in the lungs. PMID- 25132096 TI - Pattern recognition receptors: curbing gut inflammation. PMID- 25132097 TI - Incomplete bladder emptying is associated with febrile urinary tract infections in infants. AB - OBJECTIVE: To investigate lower urinary tract dysfunction in pre-toilet trained infants with and without history of febrile UTI (f-UTI). MATERIALS AND METHODS: Pre-toilet trained infants with f-UTI (Group 1) from pediatric nephrology and urology clinics, and those without f-UTI (Group 2) from infant-care centers were enrolled for the present study. Infants in Group 1 underwent four-hourly (4-H) observations for at least one month after treatment for UTI. Voided volume (VV) and post-void residual urine (PVR) were measured by weighting diaper and suprapubic ultrasound after finishing voiding, respectively. Average PVR was defined as the mean value of PVR during 4-H observation. Interrupted voiding was defined as two or three voidings within 10 min. Voiding efficiency was defined as VV/(VV+PVR). RESULTS: The mean ages of Group 1 (n=64) and Group 2 infants (n=56) were 10.6+/-7.5 months vs 10.2+/-5.1 months, respectively (p=0.70). Group 1 infants had significantly higher voiding frequency (3.0 times+/-1.2 vs 2.6 times+/-0.9, p=0.04), average PVR (14.5 ml+/-14.2 vs 8.9 ml+/-8.8, p<0.01) and lower voiding efficiency (71.2%+/-20.5 vs 80.2%+/-18.5, p=0.01) than Group 2. ROC curve analysis showed that the optimal cutoff values for PVR and voiding efficiency to differentiate Group 1 and Group 2 infants were 10 ml and 80%, respectively. Group 1 infants had significantly more repeat elevated PVR (?10 ml) and repeat low voiding efficiency (?80%) than Group 2 (44.8% vs 22.4%, p=0.03; 62.0% vs 28.6%, p<0.01, respectively). CONCLUSION: Pre-toilet trained infants with f-UTI were associated with elevated PVR and lower voiding efficiency than normal controls. PMID- 25132095 TI - Interactions between innate and adaptive lymphocytes. AB - Innate lymphocytes - including natural killer cells and the recently discovered innate lymphoid cells - have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. The contribution of the adaptive immune system to the coordination of innate lymphocyte responses is less well understood. In this Opinion article, we review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which T cells of the adaptive immune system function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential roles of regulatory and helper T cells in these processes, and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID- 25132098 TI - Midwives' experiences of the factors that facilitate normal birth among low risk women at a public hospital in Australia. AB - BACKGROUND: normal birth has major advantages for mothers and infants. Nonetheless, in the developed world, rates of normal birth have declined significantly over the past 20 years, and many women currently have caesarean section births for unclear reasons. Midwives are interested in ameliorating this trend and aim to facilitate women to have meaningful birth experiences and to achieve the best possible birth. OBJECTIVES: this project aimed to explore midwives' experiences and views of the factors that facilitate or impede normal birth. SETTING: one maternity setting in Melbourne, Australia. PARTICIPANTS: a purposive sample of 22 midwives, all with recent birthing experience, participated in in-depth interviews. METHODS: a qualitative study using an Interpretative Phenomenological approach. Interviews were audio-recorded and transcribed verbatim. Analysis was guided by Smith and Osborn's (2008) approach. FINDINGS: midwives identified a number of factors that complicated their task of facilitating normal birth. Barriers included: (1) time pressures; (2) a risk adverse culture, and; (3) women's expectations. Factors facilitating normal birth included: (1) a supporting environment, and (2) midwifery attributes and a desire to promote normal birth. KEY CONCLUSIONS: in Australia, most births take place in obstetric models of care, in which the majority of midwives are employed. The birth environment, in these units, is often risk-adverse with high rates of intervention and caesarean section. Midwives, wishing to promote normal birth in obstetric led units, face a number of challenges and often feel unsupported by senior colleagues. This situation causes conflict and gives rise to stress and unmet support needs. PMID- 25132099 TI - Effect of Lys656Asn Polymorphism of Leptin Receptor Gene on Cardiovascular Risk Factors and Serum Adipokine Levels after a High Polyunsaturated Fat Diet in Obese Patients. AB - BACKGROUND: Human obesity is characterized by high levels of leptin, and leptin levels may change with weight loss and dietary restriction. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on cardiovascular risk factors, weight loss, and serum leptin levels to a high polyunsaturated fatty acid (PUFA) hypocaloric diet in obese patients. DESIGN: A sample of 132 obese patients was analyzed in a prospective way with a dietary intervention. The enriched PUFAs hypocaloric intervention consisted in a diet of 1,459 kcal, 45.7% of carbohydrates, 34.4% of lipids, and 19.9% of proteins. RESULTS: In wild-type group, BMI (-1.9 +/- 1.4 kg/m(2) ), weight (-4.4 +/- 3.2 kg), fat mass (-4.2 +/- 3.8 kg), waist circumference (-4.1 +/- 3.1 cm), systolic blood pressure (-7.0 +/- 12.1 mmHg), diastolic blood pressure (-3.9 +/- 6.8 mmHg), insulin (-1.8 +/- 5.6 MUI/l) and HOMA-IR (-0.5 +/- 1.5 Units) decreased. In mutant genotype group, BMI (-2.0 +/- 2.1 kg/m(2) ), weight (-3.6 +/ 4.1 kg), waist circumference (-3.1 +/- 4.1 cm), total cholesterol (-25.2 +/- 19.6 mg/dl), LDL cholesterol (-16.6 +/- 25.6 mg/dl), and tryglicerides (-26.6 +/- 39.1 mg/dl) decreased. Only leptin levels have a significant decrease in wild genotype group (-6.6 +/- 10.2 ng/ml) (25.1%). CONCLUSION: Carriers of ASn656 allele have a different response than wild-type obese, with a lack of decrease in insulin levels, leptin levels, and HOMA-IR. However, obese patients with this mutant allele have a better lipid profile after weight loss. PMID- 25132100 TI - Hypertension triggers the rupture of coronary artery aneurysm in an 8-year-old boy with Kawasaki disease. PMID- 25132101 TI - Assessment of ovarian activity in captive goral (Naemorhedus griseus) using noninvasive fecal steroid monitoring. AB - To date, there is no information on gonadal steroidogenic activity of female goral (Naemorhedus griseus), a threatened species of Thailand. Captive goral populations have been established to produce animals for ex situ conservation and reintroduction, but as yet none are self-sustaining. The objectives of the present study were to (1) determine the influence of season on ovarian steriodogenic function; and (2) examine the relationship between gonadal hormone excretion and sexual behaviors throughout the year. Fecal samples were collected 5 to 7 days/wk for 15 months from 8 adult females housed at Omkoi Wildlife Breeding Center in Thailand and analyzed for ovarian steroid metabolites using validated enzyme immunoassays. Observations of sexual behaviors and mating were conducted each morning for 30 min/session. Based on fecal estrogen and progestagen metabolite concentrations, the overall estrous cycle length was about 21 days, with a 2- to 3-day follicular phase and an 18- to 20-day luteal phase. Sexual behaviors, most notably tail-up, increased for 2 to 3 days during the time estrogens were elevated during mating. Fecal progestagens were elevated during luteal phases and increased further during gestation, which lasted approximately 7 months. The lactation period was 5 months, and females were anestrus for 2 to 5 of those months, with the exception of one that cycled continuously throughout. Two females conceived around 2 months postpartum and so were pregnant during lactation. Birth records over the past 21 years indicated young are born throughout the year. This combined with the hormonal data suggests that female gorals are not strongly seasonal, at least in captivity, although there was considerable variation among females in estrogen and progestagen patterns. In conclusion, fecal steroid metabolite monitoring is an effective means of assessing ovarian function in this species and will be a useful tool for breeding management and planned development of assisted reproductive techniques such as artificial insemination and embryo transfer. PMID- 25132102 TI - Expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in human retinoblastoma. AB - BACKGROUND: Regulation of apoptosis is a complex process that involves a number of genes, including Bcl-2, Bcl-x, Bax and other Bcl-2 family members. The aim of the present study is to assess the expression of Bcl- 2 and Bax in retinoblastoma, and correlate them with clinical and histopathological parameters. METHODS: The expression of Bcl-2 and Bax proteins were examined using immunohistochemistry, Western blotting and reverse transcriptase-polymerase chain reaction in a series of 60 prospective cases of primary retinoblastoma tissues. RESULTS: Immunohistochemistry showed expression of Bcl-2 in 40/60 (66.6%), whereas Bax expression was found only in 18/60 (30%) cases, and these correlated with mRNA expression. The Western blotting results also correlated well with the immunohistochemical expression of Bcl-2 (25 kDa) and Bax (21 kDa) proteins. Bcl-2 was expressed in 96% (24/25) of invasive tumours and in 45.7% (16/35) of non invasive tumours. Expression of Bcl-2 significantly correlated with tumour invasiveness (P = 0.0274) and poor differentiation (P = 0.0163), whereas loss of Bax correlated with massive choroidal invasion and Pathological Tumor-Node Metastasis (pTNM) (P = 0.0341). However, no correlation was found between Bax and Bcl-2 expression. CONCLUSIONS: Our findings suggest that these apoptotic regulatory proteins may serve as poor prognostic markers and can be used as a therapeutic target for the treatment of invasive retinoblastoma. Further functional studies are required to explore the role of Bax and Bcl-2 in retinoblastoma. PMID- 25132103 TI - Brief report: complement C5a promotes human embryonic stem cell pluripotency in the absence of FGF2. AB - The complement activation product, C5a, is a pivotal member of the innate immune response; however, a diverse number of nonimmune functions are now being ascribed to C5a signaling, including roles during embryonic development. Here, we identify the expression of the C5a precursor protein, C5, as well as the C5a receptors, C5aR and C5L2, in both human embryonic stem cells and human-induced pluripotent stem cells. We show that administration of a physiologically relevant dose of purified human C5a (1 nM) stimulates activation of ERK1/2 and AKT signaling pathways, and is able to promote maintenance of the pluripotent state in the absence of FGF2. C5a also reduced cell loss following dissociation of human pluripotent stem cells. Our results reveal that complement C5a signaling supports human stem cell pluripotency and survival, and thus may play a key role in shaping early human embryonic development. PMID- 25132104 TI - Mechanism-specific effects of adenosine on ventricular tachycardia. AB - INTRODUCTION: There is no universally accepted method by which to diagnose clinical ventricular tachycardia (VT) due to cAMP-mediated triggered activity. Based on cellular and clinical data, adenosine termination of VT is thought to be consistent with a diagnosis of triggered activity. However, a major gap in evidence mitigates the validity of this proposal, namely, defining the specificity of adenosine response in well-delineated reentrant VT circuits. To this end, we systematically studied the effects of adenosine in a model of canine reentrant VT and in human reentrant VT, confirmed by 3-dimensional, pace- and substrate mapping. METHODS AND RESULTS: Adenosine (12 mg [IQR 12-24]) failed to terminate VT in 31 of 31 patients with reentrant VT due to structural heart disease, and had no effect on VT cycle length (age, 67 years [IQR 53-74]); ejection fraction, 35% [IQR 20-55]). In contrast, adenosine terminated VT in 45 of 50 (90%) patients with sustained focal right or left outflow tract tachycardia. The sensitivity of adenosine for identifying VT due to triggered activity was 90% (95% CI, 0.78-0.97) and its specificity was 100% (95% CI, 0.89 1.0). Additionally, reentrant circuits were mapped in the epicardial border zone of 4-day-old infarcts in mongrel dogs. Adenosine (300-400 MUg/kg) did not terminate sustained VT or have any effect on VT cycle length. CONCLUSION: These data support the concept that adenosine's effects on ventricular myocardium are mechanism specific, such that termination of VT in response to adenosine is diagnostic of cAMP-mediated triggered activity. PMID- 25132105 TI - Air pollution and emergency department visits for epistaxis. AB - OBJECTIVES: This study aimed to evaluate the association between outdoor ambient air pollution and emergency department (ED) visits for epistaxis. DESIGN: Cross sectional study, case-crossover design. SETTING: ED visit data were obtained for Edmonton, Alberta, Canada, for a period of 10 years starting 1 April 1992 and ending March 31st of 2002. The data on ED visits were supplied by Capital Health for the five major acute care hospitals in the Edmonton area. PARTICIPANTS: The analysis was performed for the population as a whole (N = 15 038) and split by sex: males (N = 8587) and females (N = 6451). MAIN OUTCOME MEASURES: We explored associations between ambient concentrations of air pollutants (CO, NO2 , SO2 , O3 , PM10 , PM2.5 ) lagged by 0-4 days and ED visits for epistaxis in Edmonton, Alberta, Canada. RESULTS: Odds ratios (ORs) and their 95% confidence intervals (CI) were reported for an increase in an interquartile range (IQR) of pollutant concentration. We obtained positive and statistically significant results for all patients with epistaxis; exposure to O3 with IQR = 14 ppb, OR = 1.05 (95% CI: 1.00-1.09, lag 0), and for males (age < 25 years), OR = 1.16 (1.03-1.30), lag 4; and to PM10 with IQR = 15 MUg/m(3) , OR = 1.02 (1.00-1.05, lag 3). These results were stronger for older (age > 24 years) females. CONCLUSIONS: These findings suggest that there may be an association between air pollutant exposure, specifically ozone and PM10 , and the number of ED visits for epistaxis. PMID- 25132106 TI - Subluminescence photodynamic therapy of recalcitrant foot warts. PMID- 25132107 TI - FrxA is an S-nitrosoglutathione reductase enzyme that contributes to Helicobacter pylori pathogenicity. AB - Helicobacter pylori is a pathogen that infects the gastric mucosa of a large percentage of the human population worldwide, and predisposes to peptic ulceration and gastric cancer. Persistent colonization of humans by H. pylori triggers an inflammatory response that leads to the production of reactive nitrogen species. However, the mechanisms of H. pylori defence against nitrosative stress remain largely unknown. In this study, we show that the NADH flavin oxidoreductase FrxA of H. pylori, besides metabolizing nitrofurans and metronidazole, has S-nitrosoglutathione reductase activity. In agreement with this, inactivation of the FrxA-encoding gene resulted in a strain that was more sensitive to S-nitrosoglutathione. FrxA was also shown to contribute to the proliferation of H. pylori in macrophages, which are key phagocytic cells of the mammalian innate immune system. Moreover, FrxA was shown to support the virulence of the pathogen upon mouse infection. Altogether, we provide evidence for a new function of FrxA that contributes to the successful chronic colonization ability that characterizes H. pylori. PMID- 25132108 TI - Efficient solar cells sensitized by porphyrins with an extended conjugation framework and a carbazole donor: from molecular design to cosensitization. AB - Porphyrin dyes containing the carbazole electron donor have been designed and optimized by wrapping the porphyrin framework, introducing an additional ethynylene bridge to extend the wavelength range of light absorption, and further suppression of the dye aggregation by introducing additional alkoxy chains. Application of a cosensitization approach results in improved current density (Jsc) and open-circuit voltage (Voc) values, thus achieving the highest cell efficiency of 10.45%. This work provides an effective combined strategy of molecular design and cosensitization for developing efficient dye-sensitized solar cells (DSSCs). In addition, carbazole has been demonstrated to be a promising donor for porphyrin sensitizers. PMID- 25132109 TI - New insights into HLA-G mediated tolerance. AB - Human Leukocyte Antigen G (HLA-G) is a nonclassical HLA class I molecule with well-characterized immunomodulatory activities. HLA-G was first described as a regulatory molecule that allows the fetus to elude the maternal immune response. In the last decade it has become evident that HLA-G is involved in modulating both innate and adaptive immune responses, in maintaining tolerance in autoimmune and inflammatory diseases and after transplantation, and in promoting immune escape in cancer and infectious diseases. HLA-G exerts its modulatory/regulatory functions directly by interacting with specific inhibitory receptors. The expression of HLA-G is finely tuned by genetic variations in the noncoding region of the locus. The recent discovery of dendritic cells-10 (DC-10) as naturally occurring HLA-G-expressing dendritic cells opens new perspectives in the identification of the molecular and cellular mechanisms underlying HLA-G-mediated tolerance. An overview on the HLA-G-mediated inhibition of innate and adaptive immune cells, on the genetic influence on HLA-G expression, and on HLA-G expressing DC-10 is presented. Moreover, we discuss the central and critical role of DC-10 in the HLA-G-mediated tolerance. PMID- 25132110 TI - Urine sample preparation for proteomic analysis. AB - Sample preparation for both environmental and more importantly biological matrices is a bottleneck of all kinds of analytical processes. In the case of proteomic analysis this element is even more important due to the amount of cross reactions that should be taken into consideration. The incorporation of new post translational modifications, protein hydrolysis, or even its degradation is possible as side effects of proteins sample processing. If protocols are evaluated appropriately, then identification of such proteins does not bring difficulties. However, if structural changes are provided without sufficient attention then protein sequence coverage will be reduced or even identification of such proteins could be impossible. This review summarizes obstacles and achievements in protein sample preparation of urine for proteome analysis using different tools for mass spectrometry analysis. The main aim is to present comprehensively the idea of urine application as a valuable matrix. This article is dedicated to sample preparation and application of urine mainly in novel cancer biomarkers discovery. PMID- 25132111 TI - Predictors of psychological functioning in children with cancer: disposition and cumulative life stressors. AB - OBJECTIVE: This study examined psychological functioning in children with a history of cancer and a matched sample of healthy peers, while exploring the roles of disposition and stressful life events. METHOD: Participants were 255 children with a history of cancer and 101 demographically matched children (8-17 years). Children completed measures of depression, anxiety, and posttraumatic stress symptoms (PTSS); history of stressful life events; and dispositional factors, including optimism and a five-factor personality measure. RESULTS: Children with cancer did not differ from peers with regard to depression and PTSS, but reported significantly lower anxiety. In hierarchical regressions, children's depression, anxiety, and PTSS scores were largely predicted by dispositional variables and, to a lesser extent, stressful life events, after controlling for demographics and health status. CONCLUSION: Children's psychological functioning is predicted primarily by disposition, and secondarily by history of stressful life events, with health status (i.e., cancer versus control) accounting for minimal, and often non-significant variance in children's functioning. These findings further support that children with cancer are generally resilient, with factors predictive of their adjustment difficulties mirroring those of children without history of serious illness. PMID- 25132112 TI - Eugenia punicifolia (Kunth) DC. as an adjuvant treatment for type-2 diabetes mellitus: a non-controlled, pilot study. AB - Type-2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type-2 DM. Fifteen patients were enrolled in a pilot, non-controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid-stimulating hormone, C-reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin-3-O-rhamnoside, quercetin-3-O-galactoside, quercetin-3-O-xyloside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, phytol, gallic acid, and trans-caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type-2 DM and deserve further investigation. PMID- 25132113 TI - Quantification of the statistical effects of spatiotemporal processing of nontask FMRI data. AB - Nontask functional magnetic resonance imaging (fMRI) has become one of the most popular noninvasive areas of brain mapping research for neuroscientists. In nontask fMRI, various sources of "noise" corrupt the measured blood oxygenation level-dependent signal. Many studies have aimed to attenuate the noise in reconstructed voxel measurements through spatial and temporal processing operations. While these solutions make the data more "appealing," many commonly used processing operations induce artificial correlations in the acquired data. As such, it becomes increasingly more difficult to derive the true underlying covariance structure once the data have been processed. As the goal of nontask fMRI studies is to determine, utilize, and analyze the true covariance structure of acquired data, such processing can lead to inaccurate and misleading conclusions drawn from the data if they are unaccounted for in the final connectivity analysis. In this article, we develop a framework that represents the spatiotemporal processing and reconstruction operations as linear operators, providing a means of precisely quantifying the correlations induced or modified by such processing rather than by performing lengthy Monte Carlo simulations. A framework of this kind allows one to appropriately model the statistical properties of the processed data, optimize the data processing pipeline, characterize excessive processing, and draw more accurate functional connectivity conclusions. PMID- 25132114 TI - Modeling nonlinear relationships in ERP data using mixed-effects regression with R examples. AB - In the analysis of psychological and psychophysiological data, the relationship between two variables is often assumed to be a straight line. This may be due to the prevalence of the general linear model in data analysis in these fields, which makes this assumption implicitly. However, there are many problems for which this assumption does not hold. In this paper, we show that, in the analysis of event-related potential (ERP) data, the assumption of linearity comes at a cost and may significantly affect the inferences drawn from the data. We demonstrate why the assumption of linearity should be relaxed and how to model nonlinear relationships between ERP amplitudes and predictor variables within the familiar framework of generalized linear models, using regression splines and mixed-effects modeling. PMID- 25132115 TI - OMIP-023: 10-color, 13 antibody panel for in-depth phenotyping of human peripheral blood leukocytes. PMID- 25132116 TI - Selective TRAIL-induced cytotoxicity to lung cancer cells mediated by miRNA response elements. AB - Lung cancer is among the most common cancers, and the current therapeutic strategies are still inefficient in most cases. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising biological agent for cancer treatment because of its potent pro-apoptotic effect on cancer cells. However, TRAIL also induces apoptosis in normal cells and therefore may cause toxicity to normal tissues if clinically applied. To address this issue, we inserted microRNA response elements (MREs) of miR-133a, miR-137 and miR-449a, which are all underexpressed in lung cancer cells, into an adenoviral vector to regulate TRAIL expression. This MRE-regulated vector (Ad-TRAIL-MRE) was able to express TRAIL in a lung-cancer-specific fashion. No TRAIL expression was detected in normal cells. Consistently, Ad-TRAIL-MRE exerted cytotoxicity to lung cancer cells, rather than normal cells, perhaps via inducing selective apoptosis. The selective TRAIL mediated growth-inhibiting effect was further confirmed in a tumour xenograft model. Also, Ad-TRAIL-MRE only resulted in very low hepatotoxicity when applied. Collectively, we generated a novel TRAIL-expressing adenoviral vector that was regulated by MREs. This strategy permits TRAIL expression in a lung-cancer specific manner and is worth further studying for clinical trials. PMID- 25132117 TI - Meta-analysis of the effect of postoperative in-hospital morbidity on long-term patient survival. AB - BACKGROUND: Major surgery is associated with high rates of postoperative complications, many of which are deemed preventable. It has been suggested that these complications not only present a risk to patients in the short term, but may also reduce long-term survival. The aim of this review was to examine the effects of postoperative complications on long-term survival. METHODS: MEDLINE, Web of Science and reference lists of relevant articles were searched up to July 2013. Studies assessing only procedure-specific, or technical failure-related, complications were excluded, as were studies of poor methodological quality. Meta analysis was performed using a random-effects model. Risk of bias was assessed using funnel plots. RESULTS: Eighteen eligible studies were included, comprising results for 134 785 patients with an overall complication rate of 22.6 (range 10.6-69) per cent. The studies included operations for both benign and malignant disease. Median follow-up was 43 (range 28-96) months. Meta-analysis demonstrated reduced overall survival after any postoperative complication for ten studies with eligible data (20 755 patients), with a hazard ratio (HR) of 1.28 (95 per cent confidence interval 1.21 to 1.34). Similar results were found for overall survival following infectious complications: HR 1.92 (1.50 to 2.35). In analyses of disease-free survival the HR was 1.26 (1.10 to 1.42) for all postoperative complications and 1.55 (1.12 to 1.99) for infectious complications. Inclusion of poor-quality studies in a sensitivity analysis had no effect on the results. CONCLUSION: Postoperative complications have a negative effect on long-term survival. This relationship appears to be stronger for infectious complications. PMID- 25132118 TI - Neuroprotective peptide-macrocycle conjugates reveal complex structure-activity relationships in their interactions with amyloid beta. AB - Interactions between amyloid beta (Abeta) and metal ions are thought to mediate the neuropathogenic effects of Abeta in Alzheimer's disease. The construction of small molecules capable of synergistically chelating metal ions and recognizing Abeta would allow new insights into the biology of this disease and provide a possible therapeutic approach. We report herein the synthesis and biological evaluation of tetraazamacrocycle-(G)KLVFF hybrids and their metal complexes. The results obtained from ThT and bis-ANS extrinsic fluorescence assays, tyrosine intrinsic fluorescence assay and proteolytic assay imply complex, multifaceted structure-activity relationships in the interaction of these conjugates with Abeta. Many of the compounds tested rescued cells from Abeta-induced cytotoxicity. The attendant simplicity and ready diversification of the synthesis of these conjugates makes them attractive for further investigation. PMID- 25132120 TI - Snacks, beverages, vending machines, and school stores: a comparison of alternative and regular schools in Minnesota, 2002 to 2008. AB - In US secondary schools, vending machines and school stores are a common source of low-nutrient, energy-dense snacks and beverages, including sugar-sweetened beverages, high-fat salty snacks, and candy. However, little is known about the prevalence of these food practices in alternative schools, which are educational settings for students at risk of academic failure due to truancy, school expulsion, and behavior problems. Nationwide, more than 5,000 alternative schools enroll about one-half million students who are disproportionately minority and low-income youth. Principal survey data from a cross-sectional sample of alternative (n=104) and regular (n=339) schools collected biennially from 2002 2008 as part of the Centers for Disease Control and Prevention Minnesota School Health Profiles were used to assess and compare food practice prevalence over time. Generalized estimating equation models were used to estimate prevalence, adjusting for school demographics. Over time, food practice prevalence decreased significantly for both alternative and regular schools, although declines were mostly modest. However, the decrease in high-fat, salty snacks was significantly less for alternative than regular schools (-22.9% vs -42.2%; P<0.0001). Efforts to improve access to healthy food choices at school should reach all schools, including alternative schools. Study findings suggest high-fat salty snacks are more common in vending machines and school stores in alternative schools than regular schools, which may contribute to increased snacking behavior among students and extra consumption of salt, fat, and sugar. Study findings support the need to include alternative schools in future efforts that aim to reform the school food environment. PMID- 25132119 TI - Attenuated improvements in adiponectin and fat loss characterize type 2 diabetes non-remission status after bariatric surgery. AB - AIM: To identify the metabolic determinants of type 2 diabetes non-remission status after bariatric surgery at 12 and 24 months. METHODS: A total of 40 adults [mean +/- sd body mass index 36 +/- 3 kg/m(2) , age 48 +/- 9 years, glycated haemoglobin (HbA1c) 9.7 +/- 2%) undergoing bariatric surgery [Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG)] were enrolled in the present study, the Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial. Type 2 diabetes remission was defined as HbA1c <6.5% and fasting glucose <126 mg/dl (i.e. <7 mmol/l) without antidiabetic medication. Indices of insulin secretion and sensitivity were calculated from plasma glucose, insulin and C-peptide values during a 120-min mixed-meal tolerance test. Body fat, incretins (glucagon-like polypeptide-1, gastric inhibitory peptide, ghrelin) and adipokines [adiponectin, leptin, tumour necrosis factor-alpha, high sensitivity C-reactive protein (hs-CRP)] were also assessed. RESULTS: At 24 months, 37 patients had available follow-up data (RYGB, n = 18; SG, n = 19). Bariatric surgery induced type 2 diabetes remission rates of 40 and 27% at 12 and 24 months, respectively. Total fat/abdominal fat loss, insulin secretion, insulin sensitivity and beta-cell function (C-peptide0-120 /glucose0-120 * Matsuda index) improved more in those with remission at 12 and 24 months than in those without remission. Incretin levels were unrelated to type 2 diabetes remission, but, compared with those without remission, hs-CRP decreased and adiponectin increased more in those with remission. Only baseline adiponectin level predicted lower HbA1c levels at 12 and 24 months, and elevated adiponectin correlated with enhanced beta-cell function, lower triglyceride levels and fat loss. CONCLUSIONS: Smaller rises in adiponectin level, a mediator of insulin action and adipose mass, characterize type 2 diabetes non-remission up to 2 years after bariatric surgery. Adjunctive strategies promoting greater fat loss and/or raising adiponectin may be key to achieving higher type 2 diabetes remission rates after bariatric surgery. PMID- 25132121 TI - Misreporting of dietary intake affects estimated nutrient intakes in low-income Spanish-speaking women. AB - Misreporting of dietary intake affects the validity of data collected and conclusions drawn in studies exploring diet and health outcomes. One consequence of misreporting is biological implausibility. Little is known regarding how accounting for biological implausibility of reported intake affects nutrient intake estimates in Hispanics, a rapidly growing demographic in the United States. Our study explores the effect of accounting for plausibility on nutrient intake estimates in a sample of Mexican-American women in northern California in 2008. Nutrient intakes are compared with Dietary Reference Intake recommendations, and intakes of Mexican-American women in a national survey are presented as a reference. Eighty-two women provided three 24-hour recalls. Reported energy intakes were classified as biologically plausible or implausible using the reported energy intakes to total energy expenditure cutoff of <0.76 or >1.24, with low-active physical activity levels used to estimate total energy expenditure. Differences in the means of nutrient intakes between implausible (n=36) and plausible (n=46) reporters of energy intake were examined by bivariate linear regression. Estimated energy, protein, cholesterol, dietary fiber, and vitamin E intakes were significantly higher in plausible reporters than implausible. There was a significant difference between the proportions of plausible vs implausible reporters meeting recommendations for several nutrients, with a larger proportion of plausible reporters meeting recommendations. Further research related to misreporting in Hispanic populations is warranted to explore the causes and effects of misreporting in studies measuring dietary intake, as well as actions to be taken to prevent or account for this issue. PMID- 25132122 TI - The effect of nopal (Opuntia ficus indica) on postprandial blood glucose, incretins, and antioxidant activity in Mexican patients with type 2 diabetes after consumption of two different composition breakfasts. AB - Nopal is a plant used in traditional Mexican medicine to treat diabetes. However, there is insufficient scientific evidence to demonstrate whether nopal can regulate postprandial glucose. The purpose for conducting this study was to evaluate the glycemic index, insulinemic index, glucose-dependent insulinotropic peptide (GIP) index, and the glucagon-like peptide 1 (GLP-1) index, and the effect of nopal on patients with type 2 diabetes after consumption of a high carbohydrate breakfast (HCB) or high-soy-protein breakfast (HSPB) on the postprandial response of glucose, insulin, GIP, GLP-1, and antioxidant activity. In study 1, the glycemic index, insulinemic index, GIP index, and GLP-1 index were calculated for seven healthy participants who consumed 50 g of available carbohydrates from glucose or dehydrated nopal. In study 2, 14 patients with type 2 diabetes consumed nopal in HCB or HSPB with or without 300 g steamed nopal. The glycemic index of nopal was 32.5+/-4, insulinemic index was 36.1+/-6, GIP index was 6.5+/-3.0, and GLP-1 index was 25.9+/-18. For those patients with type 2 diabetes who consumed the HCB+nopal, there was significantly lower area under the curve for glucose (287+/-30) than for those who consumed the HCB only (443+/-49), and lower incremental area under the curve for insulin (5,952+/-833 vs 7,313+/ 1,090), and those patients with type 2 diabetes who consumed the HSPB avoided postprandial blood glucose peaks. Consumption of the HSPB+nopal significantly reduced the postprandial peaks of GIP concentration at 30 and 45 minutes and increased the antioxidant activity after 2 hours measured by the 2,2-diphenyl-1 picrilhidracyl method. These findings suggest that nopal could reduce postprandial blood glucose, serum insulin, and plasma GIP peaks, as well as increase antioxidant activity in healthy people and patients with type 2 diabetes. PMID- 25132123 TI - Scoring of international criteria for Behcet's disease. PMID- 25132125 TI - Different responses of the melanin index to ultraviolet irradiation in relation to skin color and body site. AB - BACKGROUND/PURPOSE: Few reports describe UVB irradiation-induced pigmentation responses from different skin colors or from different body sites. This study determined pigmentation changes in skin with different colors and from different body sites following 308-nm excimer laser irradiation. METHODS: Ten healthy Korean adults were divided into light- and dark-skin groups, and irradiated body sites were divided into unexposed zones (UZ), intermittently exposed zones (IEZ), and frequently exposed zones (FEZ). Twenty-four areas were irradiated with a single 300-mJ/cm(2) shot delivered by an excimer laser. MIs were measured before irradiation, immediately after irradiation, and then 1 day, 3 days, 7 days, 14 days, and 21 days after irradiation. RESULTS: MIs declined significantly on day 1 after irradiation, particularly in light-colored skin. In the light-skin group, the MI increased from day 3 after irradiation and continued to increase for 21 days, whereas in the dark-skin group, the peak MI was reached at 7 days and declined thereafter. The peak MIs were reached at 7 days in the IEZ and FEZ and at 14 days in the UZ. CONCLUSION: Following UVB irradiation, MIs decreased, particularly in light-colored skin, before delayed tanning developed. UVB-induced pigmentation varied according to different skin colors and the body sites irradiated. PMID- 25132124 TI - Barriers to and incentives for achieving partograph use in obstetric practice in low- and middle-income countries: a systematic review. AB - BACKGROUND: The partograph is a graphic display of the progress of labour, recommended by the World Health Organization, but often underused in practice in low- and middle-income countries. We were interested in going beyond demonstration of potential efficacy - on which the existing literature concentrates - through a systematic review to identify barriers to and incentives for achieving partograph use. METHODS: We searched Ovid MEDLINE, Ovid Maternity and Infant Care, POPLINE, Web of Science, and Scopus, from 1st January 1994 to 30th September 2013, using the term 'partogra*' to include 'partograph', 'partogram', or 'partogramme'. The selection criteria were for primary or secondary research describing barriers to and incentives for partograph use in low- and middle-income countries, in English, reported in peer-reviewed publications since 1994. Thematic analysis of text on partograph use was applied to a commonly used framework for change in clinical practice, with levels describing the innovation, the individual professional, the woman, and social, organisational, economic and political contexts. RESULTS: Reported barriers to and incentives for partograph use related to the partograph itself, professional skills and practice, clinical leadership and quality assurance, and the organisational environment within the wider provision of obstetric care. Neither the evidence base for its effectiveness, nor its credibility, was reported as a barrier to use. CONCLUSION: Identifying and addressing local barriers and incentives in low- and middle-income countries, based on those in published research, could inform strategies to improve partograph use. Emerging technologies could be used to address some barriers. The thresholds for essential maternity care at which the partograph adds value should be further evaluated. PMID- 25132126 TI - Reconstructing the colonization history of lost wolf lineages by the analysis of the mitochondrial genome. AB - The grey wolves (Canis lupus) originally inhabited major parts of the Northern hemisphere, but many local populations became extinct. Two lineages of wolves in Japan, namely, Japanese or Honshu (C. l. hodophilax) and Ezo or Hokkaido (C. l. hattai) wolves, rapidly went extinct between 100 and 120years ago. Here we analyse the complete mitochondrial genome sequences from ancient specimens and reconstruct the colonization history of the two extinct subspecies. We show a unique status of Japanese wolves in wolf phylogeny, suggesting their long time separation from other grey wolf populations. Japanese wolves appeared to have colonized the Japanese archipelago in the Late Pleistocene (ca. 25,000 125,000years ago). By contrast, Ezo wolves, which are clearly separated from Japanese wolves in phylogeny, are likely to have arrived at Japan relatively recently (<14,000years ago). Interestingly, their colonization history to Japan tallies well with the dynamics of wolf populations in Europe and America during the last several millennia. Our analyses suggest that at least several thousands of wolves once inhabited in the Japanese archipelago. Our analyses also show that an enigmatic clade of domestic dogs is likely to have originated from rare admixture events between male dogs and female Japanese wolves. PMID- 25132127 TI - Metapopulations in temporary streams - the role of drought-flood cycles in promoting high genetic diversity in a critically endangered freshwater fish and its consequences for the future. AB - Genetic factors have direct and indirect impacts in the viability of endangered species. Assessing their genetic diversity levels and population structure is thus fundamental for conservation and management. In this paper we use mitochondrial and nuclear markers to address phylogeographic and demographic data on the critically endangered Anaecypris hispanica, using a broad sampling set which covered its known distribution area in the Iberian Peninsula. Our results showed that the populations of A. hispanica are strongly differentiated (high and significant FST and FST values, corroborated by the results from AMOVA and SAMOVA) and genetically diversified. We suggest that the restricted gene flow between populations may have been potentiated by ecological, hydrological and anthropogenic causes. Bayesian skyline plots revealed a signal for expansion for all populations (tMRCA between 68kya and 1.33Mya) and a genetic diversity latitudinal gradient was detected between the populations from the Upper (more diversified) and the Lower (less diversified) Guadiana river basin. We postulate a Pleistocenic westwards colonization route for A. hispanica in the Guadiana river basin, which is in agreement with the tempo and mode of paleoevolution of this drainage. The colonization of River Guadalquivir around 60kya with migrants from the Upper Guadiana, most likely by stream capture, is also suggested. This study highlights the view that critically endangered species facing range retreats (about 47% of its known populations have disappeared in the last 15years) are not necessarily small and genetically depleted. However, the extinction risk is not negligible since A. hispanica faces the combined effect of several deterministic and stochastic negative factors and, moreover, recolonization events after localized extinctions are very unlikely to occur due to the strong isolation of populations and to the patchily ecologically conditioned distribution of fish. The inferred species distribution models highlight the significant contribution of temperature seasonality and isothermality to A. hispanica occurrence in Guadiana environments and emphasize the importance of stable climatic conditions for the preservation of this species. Given the strong population structure, high percentage of private haplotypes and virtual absence of inter-basin gene flow we suggest that each A. hispanica population should be considered as an independent Operational Conservation Unit and that ex-situ and in-situ actions should be conducted in parallel to allow for the long-term survival of the species and the preservation of the genetic integrity of its populations. PMID- 25132128 TI - Mitochondrial genomes reveal the pattern and timing of marten (Martes), wolverine (Gulo), and fisher (Pekania) diversification. AB - Despite recent advances in understanding the pattern and timescale of evolutionary diversification in the marten, wolverine, fisher, and tayra subfamily Guloninae (Mustelidae, Carnivora), several important issues still remain contentious. Among these are the phylogenetic position of Gulo relative to the subgenera of Martes (Martes and Charronia), the phylogenetic relationships within the subgenus Martes, and the timing of gulonine divergences. To elucidate these issues we explored nucleotide variation in 11 whole mitochondrial genomes (mitogenomes) from eight gulonine species and two outgroup meline species. Parsimony, maximum likelihood, and Bayesian phylogenetic analyses yielded fully resolved and identical patterns of relationships with high support for all divergences. The generic status of Pekania (P. pennanti), the monophyly of the genus Martes containing M. flavigula (subgenus Charronia) to the exclusion of the genus Gulo (G. gulo), and the M. foina (M. americana (M. melampus (M. zibellina, M. martes))) phylogeny of the subgenus Martes were strongly supported. Dating analyses (BEAST) using a set of five newly applied fossil calibrations provided divergence times considerably younger than previous multigene mitochondrial estimates, but similar to multigene nuclear and nuclear-mitochondrial estimates. The 95% confidence (highest posterior density) intervals of our divergence times fell within those inferred from nuclear and nuclear-mitochondrial sequence data, and were markedly narrower than in earlier studies (whether nuclear, mitochondrial, or combined). Notably, and contrary to long-held beliefs, our findings indicate that fossils older than the Tortonian-Messinian transition (late Late Miocene) do not represent Martes, excluding from this genus its putative members from the Early, Middle, and early Late Miocene. This study demonstrates the high informativeness of the mitogenome for phylogenetic inference and divergence time estimation within Guloninae, and suggests that mitogenomes can be highly informative also for other clades at similar levels of evolutionary divergence. PMID- 25132129 TI - When everything converges: integrative taxonomy with shell, DNA and venomic data reveals Conus conco, a new species of cone snails (Gastropoda: Conoidea). AB - Cone snails have long been studied both by taxonomists for the diversity of their shells and by biochemists for the potential therapeutic applications of their toxins. Phylogenetic approaches have revealed that different lineages of Conus evolved divergent venoms, a property that is exploited to enhance the discovery of new conotoxins, but is rarely used in taxonomy. Specimens belonging to the Indo-West Pacific Conus lividus species complex were analyzed using phenetic and phylogenetic methods based on shell morphology, COI and 28S rRNA gene sequences and venom mRNA expression and protein composition. All methods converged to reveal a new species, C. conco n. sp. (described in Supplementary data), restricted to the Marquesas Islands, where it diverged recently (~3mya) from C. lividus. The geographical distribution of C. conco and C. lividus and their phylogenetic relationships suggest that the two species diverged in allopatry. Furthermore, the diversity of the transcript sequences and toxin molecular masses suggest that C. conco evolved unique toxins, presumably in response to new selective pressure, such as the availability of new preys and ecological niches. Furthermore, this new species evolved new transcripts giving rise to original toxin structures, probably each carrying specific biological activity. PMID- 25132130 TI - What do we really fear? The epidemiological characteristics of Ebola and our preparedness. AB - Ebola virus disease (hereafter Ebola) has a high fatality rate; currently lacks a treatment or vaccine with proven safety and efficacy, and thus many people fear this infection. As of August 13, 2014, 2,127 patients across four West African countries have been infected with the Ebola virus over the past nine months. Among these patients, approximately 1 in 2 has subsequently died from the disease. In response, the World Health Organization has declared the Ebola outbreak in West Africa to be a Public Health Emergency of International Concern. However, Ebola is only transmitted by patients who already present symptoms of the disease, and infection only occurs upon direct contact with the blood or body fluids of an Ebola patient. Consequently, transmission of the outbreak can be contained through careful monitoring for fever among persons who have visited, or come into contact with persons from, the site of the outbreak. Thus, patients suspected of presenting symptoms characteristic of Ebola should be quarantined. To date, South Korea is not equipped with the special containment clinical units and biosafety level 4 facilities required to contain the outbreak of a fatal virus disease, such as Ebola. Therefore, it is necessary for South Korea to make strategies to the outbreak by using present facilities as quickly as possible. It is also imperative that the government establish suitable communication with its citizens to prevent the spread of uninformed fear and anxiety regarding the Ebola outbreak. PMID- 25132131 TI - The transcription factor VvWRKY33 is involved in the regulation of grapevine (Vitis vinifera) defense against the oomycete pathogen Plasmopara viticola. AB - Grapevine (Vitis vinifera ssp. vinifera) is one of the most important fruit species; however, it is highly susceptible to various pathogens, which can cause severe crop losses in viticulture. It has been shown that several WRKY class transcription factors (TFs) are part of the signal transduction cascade, which leads to the activation of plant defense reactions against various pathogens. In the present investigation, a full-length cDNA was isolated from V. vinifera leaf tissue encoding a predicted protein, designated VvWRKY33, which shows the characteristics of group I WRKY protein family. VvWRKY33 induction correlates with the expression of VvPR10.1 (pathogenesis-related 10.1) gene in the leaves of the resistant cultivar 'Regent' after infection with Plasmopara viticola, whereas in the susceptible cultivar 'Lemberger' VvWRKY33 and VvPR10.1 are not induced. Corresponding expression of the TF and VvPR10.1 was even obtained in uninfected ripening berries. In planta, analysis of VvWRKY33 has been performed by ectopic expression of VvWRKY33 in grapevine leaves of greenhouse plants mediated via Agrobacterium tumefaciens transformation. In consequence, VvWRKY33 strongly increases resistance to P. viticola in the susceptible cultivar 'Shiraz' and reduces pathogen sporulation of about 50-70%, indicating a functional role for resistance in grapevine. Complementation of the resistance-deficient Arabidopsis thaliana Columbia-0 (Col-0) mutant line wrky33-1 by constitutive expression of VvWRKY33 restores resistance against Botrytis cinerea to wild-type level and in some complemented mutant lines even exceeds the resistance level of the parental line Col-0. Our results support the involvement of VvWRKY33 in the defense reaction of grapevine against different pathogens. PMID- 25132132 TI - Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy. AB - AIMS: Although genetic testing has been recommended in patients with hypertrophic cardiomyopathy (HCM) in current clinical practice, its utility in prognostic prediction remains to be ascertained. We assessed the dosage effect of rare variants in sarcomere genes on the long-term outcomes of HCM. METHODS AND RESULTS: A total of 529 unrelated HCM patients were prospectively recruited and followed for 4.7 +/- 3.2 years. Eight sarcomere genes were screened with targeted resequencing and identified variants were validated through Sanger sequencing. After polymorphisms and likely neutral rare variants were excluded, the patients were segregated into three groups based on the dosage of rare variants: no rare variant, a single rare variant, and multiple rare variants. Multiple rare variants were identified in 7.2% (38/529) of the study patients. Patients with multiple rare variants were younger at diagnosis, and had greater maximum LV wall thicknesses and larger left atria. The risk for cardiovascular death in patients with multiple rare variants was higher than in those without rare variants (P =10 5) or in those with a single rare variant (P = 2 * 10-5). Multivariable analysis revealed that multiple rare variants were a risk factor for cardiovascular death [hazard ratio (HR) 3.74, 95% confidence interval (CI) 1.84-7.58, P = 0.0003], as well as sudden cardiac death (HR 3.57, 95% CI 1.23-10.35, P = 0.019) and heart failure-related death (HR 4.62, 95% CI 1.67-12.76, P = 0.003). CONCLUSIONS: The presence of multiple rare variants in sarcomere genes is a risk factor for malignant outcomes in HCM, and may be appropriate to consider as a criterion in the risk stratification of HCM patients. PMID- 25132133 TI - Recent advances in germination of Clostridium spores. AB - Members of Clostridium genus are a diverse group of anaerobic spore-formers that includes several pathogenic species. Their anaerobic requirement enhances the importance of the dormant spore morphotype during infection, persistence and transmission. Bacterial spores are metabolically inactive and may survive for long times in the environment and germinate in presence of nutrients termed germinants. Recent progress with spores of several Clostridium species has identified the germinant receptors (GRs) involved in nutrient germinant recognition and initiation of spore germination. Signal transduction from GRs to the downstream effectors remains poorly understood but involves the release of dipicolinic acid. Two mechanistically different cortex hydrolytic machineries are present in Clostridium spores. Recent studies have also shed light into novel biological events that occur during spore formation (accumulation of transcriptional units) and transcription during early spore outgrowth. In summary, this review will cover all of the recent advances in Clostridium spore germination. PMID- 25132135 TI - Moderating effects of nurses' organizational justice between organizational support and organizational citizenship behaviors for evidence-based practice. AB - BACKGROUND: Lack of existing literature on the correlation among organizational justice, organizational support, and organizational citizenship behaviors has created a research gap in previous evidence-based practice (EBP) studies on nursing personnel. AIMS: To investigate whether organizational justice among nurses has a moderating effect between their organizational support and organizational citizenship behaviors in order to bridge such a gap of existing literature with the EBP study on nursing personnel. METHODS: Nursing staff of one large and influential hospital in Taiwan was surveyed. Four hundred questionnaires were distributed, and 386 were collected with a valid response rate of 96.50%. SPSS 17.0 and Amos 17.0 statistical software packages were used for data analysis. RESULTS: Nurses' organizational support positively influences their organizational citizenship behaviors, and their organizational justice perception has a positive moderating effect between organizational support and organizational citizenship behaviors. LINKING EVIDENCE TO ACTION: Results call hospitals' attention to the type of individual behaviors that may improve organizational performance. When nursing staff perceive fair and impartial treatment by the organization and supportive emotional attachment, behaviors beneficial for the organization are expressed in return. Subjective perceptions of nursing staff play an important role in organizational exchange relationship; the higher the degree of nursing staff's perceived organizational justice, the higher the degree of their organizational support, perception, and exhibition of organizational citizenship behaviors such as altruistic behavior and dedication to the work. PMID- 25132136 TI - Life history responses of Daphnia similoides simultaneously exposed to microcystin-LR and ammonia and their postexposure recovery. AB - Aquatic organisms often suffer episodic stress from cyanobacterial bloom-derived concomitants and sometimes interactive stressors, and they may recover when stressors terminate. To assess whether exposed Daphnia can quickly recover from combined toxicity of bloom-derived stressors, Daphnia similoides were exposed to mixtures of ammonia (0 mg L(-1) , 0.37 mg L(-1) , and 0.58 mg L(-1) ) and dissolved microcystin-LR (0 ug L(-1) , 10 ug L(-1) , 30 ug L(-1) , and 100 ug L( 1) ) in a full factorial design for 14 d and subsequently allowed to recover for 7 d. During the exposure, the mixtures of ammonia and microcystin-LR showed different effects on the selected variables. Ammonia delayed the time to maturation, but microcystin-LR was not negative to the development of the tested daphnids. Furthermore, microcystin-LR reduced the prolonged developmental time to first eggs and first clutch caused by high ammonia. The total reproduction of D. similoides was dramatically reduced by 64% to 79% by both toxicants and their combinations, but there were no interactive effects. After the recovery period, organisms under most treatments did not recover completely from the combined stress but showed positive signs of recovery, based on the size of the last clutch and the mean number of clutches during recovery; thus the affected D. similoides have the potential to quickly recover from the combined toxic stressors. PMID- 25132137 TI - Uncovering a broad class of fluorescent amine-containing compounds by heat treatment. AB - Amine-containing compounds including polymers, oligomers and small molecules, without conventional fluorophores, are found to emit strong visible fluorescence after a one-step heat treatment. Furthermore, our results demonstrate for the first time that not only tertiary amine groups but also primary and secondary amine groups can act as fluorescent moieties. PMID- 25132134 TI - Calcium affects OX1 orexin (hypocretin) receptor responses by modifying both orexin binding and the signal transduction machinery. AB - BACKGROUND AND PURPOSE: One of the major responses upon orexin receptor activation is Ca(2+) influx, and this influx seems to amplify the other responses mediated by orexin receptors. However, the reduction in Ca(2+) , often used to assess the importance of Ca(2+) influx, might affect other properties, like ligand-receptor interactions, as suggested for some GPCR systems. Hence, we investigated the role of the ligand-receptor interaction and Ca(2+) signal cascades in the apparent Ca(2+) requirement of orexin-A signalling. EXPERIMENTAL APPROACH: Receptor binding was assessed in CHO cells expressing human OX1 receptors with [(125) I]-orexin-A by conventional ligand binding as well as scintillation proximity assays. PLC activity was determined by chromatography. KEY RESULTS: Both orexin receptor binding and PLC activation were strongly dependent on the extracellular Ca(2+) concentration. The relationship between Ca(2+) concentration and receptor binding was the same as that for PLC activation. However, when Ca(2+) entry was reduced by depolarizing the cells or by inhibiting the receptor-operated Ca(2+) channels, orexin-A-stimulated PLC activity was much more strongly inhibited than orexin-A binding. CONCLUSIONS AND IMPLICATIONS: Ca(2+) plays a dual role in orexin signalling by being a prerequisite for both ligand-receptor interaction and amplifying orexin signals via Ca(2+) influx. Some previous results obtained utilizing Ca(2+) chelators have to be re-evaluated based on the results of the current study. From a drug discovery perspective, further experiments need to identify the target for Ca(2+) in orexin-A-OX1 receptor interaction and its mechanism of action. PMID- 25132138 TI - The prevalence of type 1 diabetes mellitus among 15-34-year-aged Lithuanian inhabitants during 1991-2010. AB - AIMS: To summarize the data on the prevalence of type 1 diabetes mellitus among 15-34-year-aged Lithuania inhabitants (1991-2010). METHODS: New prevalent cases consist of growing-up patients with diabetes onset in childhood, i.e., up to 14 years, new onset 15-34-year-aged type 1 diabetic patients Lithuanian inhabitants, and immigrants. The data on type 1 diabetes was collected with the help of general practitioners and regional endocrinologists in Lithuania. RESULTS: On 31 December 1991, there were 1202 adolescent and adult 15-34-year-aged patients with type 1 diabetes mellitus or 103.59 per 100,000 inhabitants of the same age group (95% Poisson CI 97.90-109.62), and at the end of 2010 - 1533 or 187.80 (178.63 197.44), respectively in Lithuania. During 19-year period the mean increase of type 1 diabetic patients was 1.25+/-1.94% per year or 1.47+/-2.74 per 100,000 inhabitants per mean year of the study period (for males 1.42+/-2.14% or 1.69+/ 3.05/100,000 and for females 1.05+/-1.99%, or 1.24+/-2.92/100,000). Regression based linear trends showed that the prevalence of type 1 diabetes mellitus in 15 34-year-age group had a tendency to increase among males (r=0.953; p<0.001) and females (r=0.970; p<0.001). The age adjusted prevalence frequencies for males and females in 1991 were correspondingly 102.81/100,000 and 104.55/100,000, and in 2010 - 193.75 and 182.01. CONCLUSION: The prevalence of type 1 diabetes mellitus among 15-34-year-age males and females had a tendency to increase during 1991 2010. PMID- 25132139 TI - Metabolic control and therapeutic profile of patients with diabetes in Portuguese primary care (TEDDI CP). AB - AIM: To evaluate the metabolic control rate and to characterize the therapeutic profile of patients with Type 2 diabetes mellitus (DM2) from Portuguese primary care of National Health Service. METHODS: Cross-sectional multicentre study conducted in Portuguese primary health care units between July 2011 and May 2012. A national representative sample of 1528 DM2 patients was selected from 51 units, stratified by region. Socio-demographic, anthropometric, lifestyle, cardiometabolic risk factors, disease status, HbA1c levels and therapeutic information were collected. RESULTS: Patients' mean age was 65+/-10.7 years (50.4% males) and median duration of disease was 7 years: range (0-45 years). Almost 8% were smokers, 80.3% had hypertension, 61.6% hypercholesterolemia and almost 15% cardiovascular disease. Patients' health condition was classified with a score of 4 or 5 (excellent) for 60.6%. Median HbA1c was 6.6% (min-max: 4.2% 13.4%), 64.8% of the patients had HbA1c<7.0% and 49.2% HbA1c<=6.5%. Oral antidiabetics were used in 94.4% of the patients, antihypertensives in 80.6%, antidyslipidemics in 72.0%, antiplatelet agents in 50.6% and insulin in 8.3%. CONCLUSIONS: Metabolic control rate was good according to current guidelines. However, patients with higher HbA1c levels had longer time since diagnosis, worse current health condition, hypertriglyceridemia and were insulin-treated. PMID- 25132140 TI - Evaluation of knowledge regarding gestational diabetes mellitus and its association with glycaemic level: A Malaysian study. AB - AIMS: The aim of this study was to evaluate the knowledge about GDM and its corresponding relation with glycaemic level in GDM patients. METHOD: A cross sectional study was conducted in antenatal clinic of Hospital Pulau Pinang, Malaysia from June 2013 to December 2013 using Gestational Diabetes Mellitus Knowledge Questionnaire (GDMKQ) on the sample of 175 GDM patients. Three most recent fasting plasma glucose (FPG) values (mmol/l) were taken from patients profiles and mean was calculated. RESULTS: A total of 166 patients were included in final analysis. A total mean knowledge score of 166 patients was 10.01+/-3.63 and total mean FPG value was 5.50+/-1.13. Knowledge had a significant negative association with FPG (r=- 0.306, P<0.01). Among different knowledge domains, highest mean score was seen for diet/food values domain and lowest for management of GDM. Educational level seems to be the most significant predictor of GDM knowledge and glycaemic control. Highest mean knowledge score and lowest mean glycaemic levels were recorded for patients aged 25-29 years, Malay ethnicity, working women and family history of DM. CONCLUSION: Higher Knowledge about GDM is related to better glycaemic control. New educational strategies should be developed to improve the lower health literacy. PMID- 25132141 TI - Morphological and proteomic characterization of midgut of the malaria vector Anopheles albimanus at early time after a blood feeding. AB - The midgut of anopheline mosquito is the entry of Plasmodium, the causative agent of malaria.When the mosquito feeds on parasite infected host, Plasmodium parasites reach the midgut and must confront digestive enzymes, the innate immune response and go across the peritrophic matrix (PM), a thick extracellular sheath secreted by the mosquito midgut epithelial cells. Then, to continue its development, the parasite must reach the salivary glands to achieve transmission to a vertebrate host. We report here the morphological and biochemical descriptions of the midgut changes after a blood meal in Anopheles albimanus. Before blood feeding, midgut epithelial cells contained numerous electrondense vesicles distributed in the central to apical side. These vesicles were secreted to the luminal side of the midgut after a blood meal. At early times after blood ingest, the PM is formed near microvilli as a granulous amorphous material and after it consolidates forming a highly organized fibrillar structure, constituted by layers of electrondense and electronlucent regions. Proteomic comparative analysis of sugar and blood fed midguts showed several molecules that modify their abundance after blood intake; these include innate immunity, cytoskeletal, stress response, signaling, and digestive, detoxifying and metabolism enzymes. Biological significance In the midgut of mosquitoes during bloodfeeding, many simultaneous processes occur, including digestion, innate immune activities, cytoskeleton modifications, construction of a peritrophic matrix and hormone production, between others. Mechanical forces are very intense during bloodfeeding and epithelial and muscular cells must resist the stress, modifying the actin cytoskeleton and coordinating intracellular responses by signaling. Microorganisms present in midgut contents reproduce and interact with epithelial cells triggering innate immune response. When infectious agents are present in the blood meal they must traverse the peritrophic matrix, an envelope formed from secretion products of epithelial cells, and evade the immune system in order to reach the epithelium and continue their journey towards salivary glands, in preparation for the transmission to the new hosts. During all these processes, proteins of mosquitoes are modified in order to deal with mechanical and biological challenges, and the aim of this work is to study these changes. PMID- 25132142 TI - Data worth and prediction uncertainty for pesticide transport and fate models in Nebraska and Maryland, United States. AB - BACKGROUND: Complex environmental models are frequently extrapolated to overcome data limitations in space and time, but quantifying data worth to such models is rarely attempted. The authors determined which field observations most informed the parameters of agricultural system models applied to field sites in Nebraska (NE) and Maryland (MD), and identified parameters and observations that most influenced prediction uncertainty. RESULTS: The standard error of regression of the calibrated models was about the same at both NE (0.59) and MD (0.58), and overall reductions in prediction uncertainties of metolachlor and metolachlor ethane sulfonic acid concentrations were 98.0 and 98.6% respectively. Observation data groups reduced the prediction uncertainty by 55-90% at NE and by 28-96% at MD. Soil hydraulic parameters were well informed by the observed data at both sites, but pesticide and macropore properties had comparatively larger contributions after model calibration. CONCLUSIONS: Although the observed data were sparse, they substantially reduced prediction uncertainty in unsampled regions of pesticide breakthrough curves. Nitrate evidently functioned as a surrogate for soil hydraulic data in well-drained loam soils conducive to conservative transport of nitrogen. Pesticide properties and macropore parameters could most benefit from improved characterization further to reduce model misfit and prediction uncertainty. PMID- 25132143 TI - Efficacy of combination therapy of oral zinc sulfate with imiquimod, podophyllin or cryotherapy in the treatment of vulvar warts. AB - AIM: Zinc sulfate is beneficial in the treatment of epithelial warts. We conducted this study to compare the efficacy of combination therapy of oral zinc sulfate with conventional treatments in the treatment of vulvar warts. MATERIAL AND METHODS: This study was a randomized controlled trial. The sample size was 42 in each group. Women aged 20-50 years were placed by the block randomized method into six groups: the podophyllin-, imiquimod- and cryotherapy-treated groups, and another three groups receiving 8-week combination therapy of 400 mg oral zinc sulfate with one of the above-mentioned treatments. Data were analyzed using anova and Fischer's exact test with spss16. RESULTS: A total of 228 patients were recruited and completed the study in six treatment groups. No significant difference was observed in the response to treatment among these groups. Relapse after 6 months was significantly higher in the podophyllin-, imiquimod- and cryotherapy-treated patients compared to patients receiving these treatments in combination with oral zinc sulfate (P<0.05). CONCLUSIONS: Combined therapy of oral zinc sulfate with conventional treatments of vulvar warts appears to reduce the relapse rate. PMID- 25132144 TI - Treatment with Evasin-3 abrogates neutrophil-mediated inflammation in mouse acute pancreatitis. AB - BACKGROUND: Acute pancreatitis is characterized by inflammatory processes affecting not only the pancreas, but also the lung. Here, we investigated timing of leucocyte infiltration and chemokine expression within lung and pancreas during pancreatitis and whether treatments selectively inhibiting chemokines (using Evasins) could improve organ injury. MATERIAL AND METHODS: C57Bl/6 mice were submitted in vivo to 10-h intraperitoneal injections of cerulein and followed for up to 168 h. Five minutes after the first cerulein injection, a single intraperitoneal injection of 10 MUg Evasin-3, 1 MUg Evasin-4 or an equal volume of vehicle (PBS) was performed. Leucocytes, reactive oxygen species (ROS), necrosis and chemokine/cytokine mRNA expression were assessed in different organs by immunohistology and real-time RT-PCR, respectively. RESULTS: In the lung, neutrophil infiltration and macrophage infiltration peaked at 12 h and were accompanied by increased CXCL2 mRNA expression. CCL2, CXCL1 and TNF-alpha significantly increased after 24 h as compared to baseline. No increase in CCL3 and CCL5 was observed. In the pancreas, neutrophil infiltration peaked at 6 h, while macrophages increased only after 72 h. Treatment with Evasin-3 decreased neutrophil infiltration, ROS production and apoptosis in the lung and reduced neutrophils, macrophages apoptosis and necrosis in the pancreas. Evasin-4 only reduced macrophage content in the lung and did not provide any benefit at the pancreas level. CONCLUSION: Chemokine production and leucocyte infiltration are timely regulated in lung and pancreas during pancreatitis. CXC chemokine inhibition with Evasin-3 improved neutrophil inflammation and injury, potentially interfering with damages in acute pancreatitis and related pulmonary complications. PMID- 25132145 TI - Quantitative volatile compound profiles in fungal cultures of three different Fusarium graminearum chemotypes. AB - Biosynthesis in fungal cultures of 27 Fusarium graminearum isolates of three different chemotypes (3AcDON, 15AcDON and NIV) grown on yeast extract sucrose agar medium was examined in this study. Volatile organic compound (VOC) analysis performed by headspace solid phase microextraction GC-MS allowed for determination of various concentrations of six alcohols, 14 aldehydes and ketones, 10 benzene derivatives, one furane, five hydrocarbons and three terpenes. In general, the determined VOC profile in fungal cultures was dominated by hexanal (up to 74%), followed by nonanal (18%) and 2-methylbutanal (18%). Principal component analysis and discriminant analysis based on VOCs allowed for unambiguous discrimination of all studied isolates into three different groups in accordance with their trichothecene production (chemotypes). Significant differences were revealed between the levels of aldehydes and ketones, benzene derivatives and hydrocarbons in fungal cultures of three F. graminearum chemotypes. PMID- 25132146 TI - Development and usability of a computer-tailored pedometer-based physical activity advice for breast cancer survivors. AB - This observational study aimed to adapt a computer-tailored step advice for the general population into a feasible advice for breast cancer survivors and to test its usability. First, several adaptations were made to the original design (adding cancer-related physical activity (PA) barriers and beliefs, and self management strategies to improve survivors' personal control). Second, the adapted advice was evaluated in two phases: (1) a usability testing in healthy women (n = 3) and survivors (n = 6); and (2) a process evaluation during 3 weeks in breast cancer survivors (n = 8). Preliminary usability testing revealed no problems during logging-in; however, three survivors misinterpreted some questions. After refining the questionnaire and advice, survivors evaluated the advice as interesting, attractive to read, comprehensible and credible. Inactive survivors found the advice novel, but too long. The process evaluation indicated that the majority of the women (n = 5/8) reported increased steps. Monitoring step counts by using a pedometer was perceived as an important motivator to be more active. To conclude, this study provides initial support for the usability and acceptability of a computer-tailored pedometer-based PA advice for breast cancer survivors. After testing efficacy and effectiveness of this intervention, this tool can broaden the reach of PA promotion in breast cancer survivors. PMID- 25132147 TI - Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors. AB - Hepatitis B envelope antigen (HBeAg) seroconversion represents an endpoint of treatment of chronic hepatitis B virus (HBV) infections. We have studied whether levels of serum HBV RNA during polymerase inhibitor treatment might be helpful for predicting HBeAg seroconversion. HBV RNA levels were determined in serial serum samples from 62 patients with chronic HBV infection (50 HBeAg positive). Patients received antiviral treatment for a mean duration of 30 +/- 15 (range, 4 64) months. A new rapid amplification of complimentary DNA-ends-based real-time polymerase chain reaction was established for quantitative analysis of polyadenylated full-length (fl) and truncated (tr) HBV RNA. HBV RNA, HBV DNA, and hepatitis B surface antigen (HBsAg) levels as well as presence of HBeAg and hepatitis B envelope antibody were measured at baseline, month 3, month 6, and subsequent time points. Fifteen patients who achieved HBeAg seroconversion after a mean duration of 19 +/- 14 (range, 3-56) months of antiviral treatment showed a significantly stronger decline in mean HBV flRNA and trRNA levels from baseline to month 3 of 1.0 +/- 1.4 (range, -1.6-3.4) and 2.1 +/- 1.4 (range, 0-3.9) and to month 6 of 1.8 +/- 1.4 (range, 0-4.6) and 3.1 +/- 1.7 (range, 0-5.1) log10 copies/mL, respectively, in comparison to 35 HBeAg-positive patients without HBeAg seroconversion (P < 0.001 for months 3 and 6). A similar decline in HBV RNA levels was observed in HBeAg-negative patients. The decline of HBV RNA levels at months 3 and 6 of treatment was to be the strongest predictor of HBeAg seroconversion, when compared to levels of HBV DNA, HBsAg, alanine aminotransferase, and HBV genotype, age, and sex. CONCLUSION: Serum HBV RNA levels may serve as a novel tool for prediction of serological response during polymerase inhibitor treatment in HBeAg-positive patients. PMID- 25132148 TI - Predictors of early poor aesthetic outcome after breast-conserving surgery in patients with breast cancer: initial results of a prospective cohort study at a single institution. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to explore features of patients reporting early poor aesthetic outcome after simple breast-conserving surgery. METHODS: We prospectively evaluated 709 patients shortly after breast conserving surgery. Aesthetic outcome was measured by aesthetic status scores of the Breast Cancer Treatment Outcome Scale. Clinical, surgical, and pathologic variables were assessed to identify predictors of poor aesthetic outcome. RESULTS: Poor aesthetic outcome was reported by 46 (6.5%) patients, and 209 (29%) patients reported an intermediate aesthetic outcome. A single factor analysis of variance showed a negative impact of higher specimen weight (P < 0.001). Univariate logistic regression analysis revealed the following significant risk factors for poor aesthetic outcome: 12 o'clock positioning of tumor localization, a tumor behind the nipple areolar complex (NAC), fishmouth-shaped incision with resection of the NAC, quadrantectomy, central segmental resection, and pT stages 3 and 4. Multivariate logistic regression analysis indicated statistically independent associations between poor aesthetic outcome and tumor position in the inner half of the breast or behind the NAC, quadrantectomy, and pT stages 3 and 4. CONCLUSION: Poor aesthetic outcome is relatively rare shortly after breast conserving surgery, but predictable in specific situations. PMID- 25132149 TI - The importance of parental knowledge: evidence from weight report cards in Mexico. AB - The rise of childhood obesity in less developed countries is often overlooked. We study the impact of body weight report cards in Mexico. The report cards increased parental knowledge and shifted parental attitudes about children's weight. We observe no meaningful changes in parental behaviors or children's body mass index. Interestingly, parents of children in the most obese classrooms were less likely to report that their obese child weighed too much relative to those in the least obese classrooms. As obesity rates increase, reference points for appropriate body weights may rise, making it more difficult to lower obesity rates. PMID- 25132150 TI - The kinematic relationship between sitting and standing posture and pelvic inclination and its significance to cup positioning in total hip arthroplasty. AB - PURPOSE: The aim of this study is to describe the influence of sitting and standing posture on sagittal pelvic inclination in total hip replacement patients to assist with correct acetabular component positioning. METHODS: Lateral radiographs of the pelvis and lumbar spine in sitting and standing positions were extracted. Pelvic tilt was measured using the vertical inclination of a line from the anterior superior iliac spine (ASIS) to pubic tubercle. Sacral inclination, Cobb angle of the lumbar spine and hip flexion were recorded. RESULTS: Sixty patients were identified with a mean age of 63. Men were more likely to flex the lumbar spine in sitting (p = 0.004); 80 degrees of hip flexion is required for seated posture. Stiff hips required compensatory pelvic flexion and lumbar flexion in sitting. There is a linear relationship between hip flexion and pelvic tilt, hip flexion and lumbar lordosis. CONCLUSIONS: Pelvic orientation is determined by lumbar and hip stiffness. This impacts on acetabular version. PMID- 25132151 TI - Brain derived neurotrophic factor gene (BDNF) and personality traits: the modifying effect of season of birth and sex. AB - Personality traits are complex phenotypes influenced by interactions of multiple genetic variants of small effect and environmental factors. It has been suggested that the brain derived neurotrophic factor gene (BDNF) is involved in personality traits. Season of birth (SOB) has also been shown to affect personality traits due to its influences on brain development during prenatal and early postnatal periods. The present study aimed to investigate the effects of BDNF on personality traits; and the modifying effects of SOB and sex on associations between BDNF and personality traits. A sample of 1018 young adults (68% women; age range 17-25years) of Caucasian origin from the Russian Federation was assessed on personality traits (Novelty Seeking, Harm Avoidance, Reward Dependence, Persistence, Self-directedness, Cooperativeness, Self-transcendence) with the Temperament and Character Inventory-125 (TCI-125). Associations between personality traits and 12 BDNF SNPs were tested using linear regression models. The present study demonstrated the effect of rs11030102 on Persistence in females only (PFDR=0.043; r(2)=1.3%). There were significant interaction effects between Val66Met (rs6265) and SOB (PFDR=0.048, r(2)=1.4%), and between rs2030323 and SOB (PFDR=0.042, r(2)=1.3%), on Harm Avoidance. Our findings provide evidence for the modifying effect of SOB on the association between BDNF and Harm Avoidance, and for the modifying effect of sex on the association between BDNF and Persistence. PMID- 25132152 TI - microRNAs: role in leukemia and their computational perspective. AB - MicroRNAs (miRNAs) belong to the family of noncoding RNAs (ncRNAs) and had gained importance due to its role in complex biochemical pathways. Changes in the expression of protein coding genes are the major cause of leukemia. Role of miRNAs as tumor suppressors has provided a new insight in the field of leukemia research. Particularly, the miRNAs mediated gene regulation involves the modulation of multiple mRNAs and cooperative action of different miRNAs to regulate a particular gene expression. This highly complex array of regulatory pathway network indicates the great possibility in analyzing and identifying novel findings. Owing to the conventional, slow experimental identification process of miRNAs and their targets, the last decade has witnessed the development of a large amount of computational approaches to deal with the complex interrelations present within biological systems. This article describes the various roles played by miRNAs in regulating leukemia and the role of computational approaches in exploring new possibilities. PMID- 25132153 TI - A note on the efficiencies of sampling strategies in two-stage Bayesian regional fine mapping of a quantitative trait. AB - In focused studies designed to follow up associations detected in a genome-wide association study (GWAS), investigators can proceed to fine-map a genomic region by targeted sequencing or dense genotyping of all variants in the region, aiming to identify a functional sequence variant. For the analysis of a quantitative trait, we consider a Bayesian approach to fine-mapping study design that incorporates stratification according to a promising GWAS tag SNP in the same region. Improved cost-efficiency can be achieved when the fine-mapping phase incorporates a two-stage design, with identification of a smaller set of more promising variants in a subsample taken in stage 1, followed by their evaluation in an independent stage 2 subsample. To avoid the potential negative impact of genetic model misspecification on inference we incorporate genetic model selection based on posterior probabilities for each competing model. Our simulation study shows that, compared to simple random sampling that ignores genetic information from GWAS, tag-SNP-based stratified sample allocation methods reduce the number of variants continuing to stage 2 and are more likely to promote the functional sequence variant into confirmation studies. PMID- 25132154 TI - PCR-based prediction of type I beta-exotoxin production in Bacillus thuringiensis strains. AB - Some Bacillus thuringiensis strains secrete type I beta-exotoxin, which is a non specific insecticidal and thermostable adenine nucleoside oligosaccharide. Toxicity bioassays and HPLC are traditional methods for detecting beta-exotoxin. With the aim of establish a first rapid approach for prediction of type I beta exotoxin production, two PCR-based methods were successfully evaluated in B. thuringiensis strains and native isolates. In order to validate a reliable technology, results obtained by this method were correlated with that obtained from Musca domestica bioassays. PMID- 25132155 TI - Metabolite profile deviations in an oral glucose tolerance test-a comparison between lean and obese individuals. AB - OBJECTIVE: While impaired glucose tolerance diagnosed by the oral glucose tolerance test (OGTT) is a common trait in obese individuals, less is known about changes in levels of other metabolites. The aim was to reveal the complex alterations in metabolite levels provoked by an OGTT and its perturbation in obese individuals. METHODS: Gas chromatography/mass spectrometry was used to profile metabolite levels in serum from 14 obese participants (body mass index [BMI] of 43.6 +/- 1.5 kg m(-2) [mean +/- SEM]) at 0, 30, and 120 min during a standard 2-h 75 g OGTT. Metabolite profiles from six lean individuals (BMI of 22.4 +/- 2.4 kg m(-2) ), collected from a previous study, were included for comparison. RESULTS: In the obese group, 59 metabolite profiles were determined. Among these, 16 deviated from profiles in the lean group. Deviating metabolites were categorized into three groups. Delayed reduction in levels of five fatty acids. Increased levels at 30 min of five amino acids, including isoleucine and leucine. A blunted increase at 30 min of six metabolites. CONCLUSIONS: Metabolomics analysis revealed distinct differences in alterations of metabolite levels during an OGTT in obese and lean subjects. To this end, our data suggests a disrupted regulation of ketogenesis, lipolysis and proteolysis in obese individuals. PMID- 25132156 TI - Four-component fluorescence of trans-1,2-di(1-methyl-2-naphthyl)ethene at 77 K in glassy media. Conformational subtleties revealed. AB - The vibronic structure of the fluorescence spectrum of trans-1,2-di(1-methyl-2 naphthyl)ethene (t-1,1) in methylcyclohexane (MCH) solution at room temperature was expected to become better defined upon cooling of the solution to 77 K. Instead, a broad, lambdaexc-dependent fluorescence spectrum was observed in the glassy medium. Vibronically structured t-1,1 fluorescence spectra were obtained in the MCH glass only upon irradiation at the long-lambda onset of the absorption spectrum. The application of singular value decomposition with self-modeling on the fluorescence spectral matrices of t-1,1 allowed their resolution into major and minor pairs of vibronically structured spectra that are assigned to two structural modifications of each of two relative orientations of the 1-methyl-2 naphthyl moieties. The difference between the two structures in each pair lies in the direction of rotation of each naphthyl group away from the plane of the olefinic bond. A complex but different conformer distribution is also responsible for the fluorescence spectra of t-1,1 in 5:5:2 (v/v/v) diethyl ether/isopentane/ethyl alcohol (EPA) glass at 77 K. The conformer distributions are also sensitive to the rate of cooling used in glass formation. Conformer distributions based on predicted small energy differences from gas-phase theoretical calculations are of little value when applied to volume-constraining media. The photophysical and photochemical properties of the analogues of the other two conformers of trans-1,2-di(2-naphthyl)ethene, trans-1-(1-methyl-2 naphthyl)-2-(3-methyl-2-naphthyl)ethene (t-1,3) and trans-1,2-di(3-methyl-2 naphthyl)ethene (t-3,3), were determined in solution. However, it is the calculated geometries and energy differences of the t-1,1 conformers [DFT using B3LYP/6-311+G(d,p)] that are essential guides to the interpretation of the experimental results. PMID- 25132157 TI - The politics of unsafe abortion in Burkina Faso: the interface of local norms and global public health practice. AB - In Burkina Faso, abortion is legally restricted and socially stigmatised, but also frequent. Unsafe abortions represent a significant public health challenge, contributing to the country's very high maternal mortality ratio. Inspired by an internationally disseminated public health framing of unsafe abortion, the country's main policy response has been to provide post-abortion care (PAC) to avert deaths from abortion complications. Drawing on ethnographic research, this article describes how Burkina Faso's PAC policy emerged at the interface of political and moral negotiations between public health professionals, national bureaucrats and international agencies and NGOs. Burkinabe decision-makers and doctors, who are often hostile to induced abortion, have been convinced that PAC is 'life-saving care' which should be delivered for ethical medical reasons. Moreover, by supporting PAC they not only demonstrate compliance with international standards but also, importantly, do not have to contend with any change in abortion legislation, which they oppose. Rights-based international NGOs, in turn, tactically focus on PAC as a 'first step' towards their broader institutional objective to secure safe abortion and abortion rights. Such negotiations between national and international actors result in widespread support for PAC but stifled debate about further legalisation of abortion. PMID- 25132158 TI - Effects of magnesium sulphate on coagulation after laparoscopic colorectal cancer surgery, measured by rotational thromboelastometry (ROTEM(r) ). AB - We investigated the effects of magnesium sulphate on blood coagulation profiles using rotational thromboelastometry in patients undergoing laparoscopic colorectal cancer surgery. Patients were randomly allocated to the magnesium group (n = 22) or control group (n = 22). The magnesium group received intravenous magnesium sulphate (50 mg.kg(-1) followed by a continuous infusion of 15 mg.kg(-1) .h(-1) ), whereas the control group received the same volume of isotonic saline. Mean (SD) postoperative serum magnesium levels were 1.60 (0.13) mmol.l(-1) in the magnesium group compared with 0.98 (0.06) mmol.l(-1) in the control group (p < 0.001). All maximum clot firmness values of ROTEM analysis were significantly lower on the third postoperative day in the magnesium group compared with the control group (p < 0.05). We conclude that ROTEM analysis demonstrated that intra-operative administration of intravenous magnesium sulphate reduces blood hypercoagulability in patients undergoing laparoscopic colorectal cancer surgery. PMID- 25132159 TI - Steroid-induced ocular hypertensive response in children and adolescents with acute lymphoblastic leukemia and non-Hodgkin lymphoma. AB - The aim of this study was to evaluate intraocular pressure (IOP) associated with use of glucocorticoids in children and adolescents treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma. We carried out a prospective descriptive study with measurement of IOP before treatment (D0), 8th (D8), 14th (D14), and 28 h days (D28) of treatment. We examined 12 patients, with two cases of ocular hypertension, and it was found a statistically significant difference between the means of IOP between D0 versus D8 and D0 versus D14 (P = 0.013). The possibility of silent ocular hypertension with irreversible blindness indicates the need of IOP verification. PMID- 25132160 TI - Can implanted venous access ports remain patent without maintenance flush-lock? PMID- 25132161 TI - Multisite phosphorylation of Bcl-2 via protein kinase Cdelta facilitates apoptosis of hypertrophic cardiomyocytes. AB - Activated protein kinase Cdelta (PKCdelta) associated with cardiac hypertrophy moves from the cytoplasm to the mitochondria and subsequently triggers the apoptotic signalling pathway. The underlying mechanisms remain unknown. The aim of the present study was to investigate whether mitochondrial translocation of PKCdelta phosphorylates multiple sites of Bcl-2, resulting in an imbalance between Bcl-2 and Bak or Bax, thus enhancing the susceptibility of hypertrophic cardiomyocytes to angiotensin II (AngII)-induced apoptosis. Chronic pressure overload was induced by transverse aortic constriction (TAC) in rats. The apoptotic rate increased in hypertrophied cardiomyocytes. In AngII-treated hearts (10 nmol/L, 60 min), there was an increase in the number of TERMINAL deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL)-positive cells; PKCdelta inhibition with 500 nmol/L deltaV1-1 for 60 min prevented the AngII-induced increase in apoptosis. In the hypertrophied myocardium, PKCdelta expression increased, whereas that of Bcl-2 decreased compared with the synchronous control. Treatment of hearts with 10 nmol/L AngII for 60 min activated PKCdelta and induced translocation of PKCdelta to the mitochondria, where activated PKCdelta facilitated the phosphorylation of Bcl-2 at serine-87 and serine-70 sites. The multisite phosphorylated Bcl-2 was released from the mitochondria, and exhibited reduced affinity for Bak and Bax. The imbalance between Bcl-2 and Bak/Bax induced the release of mitochondrial cytochrome c and then activated the caspase 3 apoptotic pathway during AngII stimulation (10 nmol/L, 60 min) of hypertrophied cardiomyocytes. Inhibition of PKCdelta reduced these effects of AngII. The results suggest that PKCdelta can counteract the anti-apoptotic effect of Bcl-2 and may promote cardiomyocyte apoptosis through multisite phosphorylation of Bcl-2 in hypertrophied cardiomyocytes. PMID- 25132162 TI - HPV and Chlamydia trachomatis co-detection in young asymptomatic women from high incidence area for cervical cancer. AB - Chlamydia trachomatis causing chronic inflammatory diseases has investigated as possible human papillomavirus (HPV) cofactor in cervical cancer. The aim of this study is to evaluate the prevalence of Chlamydia trachomatis and HPV co-infection in different cohorts of asymptomatic women from a Northern Italy area at high incidence for cervical cancer. Cervical samples from 441 females were collected from Cervical Cancer Screening Program, Sexually Transmitted Infectious and Assisted Reproductive Technology centres. HPV and Chlamydia trachomatis were detected simultaneously and genotyped using a highly sensitive bead based assay. The overall prevalence of Chlamydia trachomatis was estimated 9.7%, in contrast with the reported national data of 2.3%, and co-infection with HPV was diagnosed in the 17% of the samples. In females <= 25 years of age, the infection reached a peak of 22% and co-infection with HPV of 45.8% (P < 0.001). Of note, in young females diagnosed with low grade cervical lesions, no significant difference between Chlamydia trachomatis and HPV distribution was observed, while differently, HPV co-infection was found significantly associated to the presence of intraepithelial lesions when compared to older females (20% vs. 1%; P < 0.001). In this study, the use of a high sensitive molecular technique exhibited higher analytical sensitivity than the referred assays for the diagnosis of Chlamydia trachomatis and HPV co-infection in asymptomatic females, leading to reduction of the potential to identify incorrectly the infection status. An active screening for timely treatment of Chlamydia trachomatis infection is suggested in young females to evaluate a possible decrease in incidence of pre cancer intraepithelial lesions. PMID- 25132163 TI - Multidisciplinary consensus: a practical guide for the integration of abiraterone into clinical practice. AB - Abiraterone improves survival, relieves pain, improves quality of life and extends time to prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC). A consensus-based guide for using abiraterone in patients with mCRPC has been developed by Australian clinicians with expertise in prostate cancer, based on their experience and supported by published data. Recommendations were developed for eight key topics: abiraterone administration; steroid administration and duration of use; concomitant medications and drug interactions; timing of testing and monitoring response; safety in different populations; potential toxicities; precautions and contraindications; and referral and multidisciplinary care. Abiraterone is taken orally in a fasting state. Symptoms associated with mineralocorticoid excess are managed by coadministration of low-dose prednisone or prednisolone. Potassium levels, blood pressure and liver function need to be tested frequently during the early treatment phase. Response to treatment is monitored based on symptoms, radiological imaging and PSA levels. Potential adverse consequences of long-term steroid therapy on bone and metabolic health need to be screened for and managed. Advanced prostate cancer is best managed by a multidisciplinary team and early referral should be considered. Questions about the potential use of abiraterone in early disease and in combination with other therapies are being addressed in ongoing clinical trials. PMID- 25132164 TI - Retrospective clinical evaluation of hypobaric spinal anaesthesia in dogs undergoing pelvic limb orthopaedic surgery. AB - OBJECTIVE: To evaluate intraoperative effects, complications, postoperative rescue analgesia requirement and presence of postoperative unilateral blockade after hypobaric spinal anaesthesia in dogs. METHODS: Retrospective review of case records of dogs that underwent pelvic limb orthopaedic surgery and received hypobaric spinal anaesthesia. Cases that contained complete information on perioperative analgesia, end tidal anaesthetic agent, arterial blood pressure, postoperative urination, motor function and assessment at the sixth week re examination were selected. RESULTS: Twenty-four of forty-eight records were sufficiently complete to meet the selection criteria. Local anaesthetic dose and volume of the solution administered were 0 . 22 (+/-0 . 06) mg/kg and 0 . 16 (+/ 0 . 05) mL/kg, respectively. Fentanyl was administered intraoperatively in seven dogs (29%); mean +/- sd end-expired isoflurane was 1 . 09 +/- 0 . 17%; hypotension was observed in nine dogs (37 . 5%). Unilateral blockade was documented in 18 dogs (75%); 6 dogs (25%) required methadone postoperatively; urinary retention was not observed. One dog developed steroid responsive meningitis arteritis. CLINICAL SIGNIFICANCE: Hypobaric spinal anaesthesia achieved unilateral postoperative pelvic limb motor blockade in dogs, although bilateral block occurred in a proportion of animals; intraoperative hypotension was not infrequent. Fentanyl and postoperative methadone might be required to control nociception and pain, despite technical success in performing spinal anaesthesia. PMID- 25132165 TI - Reproductive factors and non-Hodgkin lymphoma: a systematic review. AB - Considerable efforts have been made to elucidate non-Hodgkin lymphoma's (NHL) etiology during the last decades. Some evidence points to an association with reproductive factors, as incidence rates for most NHL subtypes are usually higher in men than in women, and several subtypes express hormonal receptors. Although the evidence is not compelling, some studies show an inverse association with gravidity. Associations with postmenopausal hormone therapy are usually derived from unopposed estrogen use, rather than for the combination of estrogen with progestin, but these findings vary by study design. Inconsistencies in the results are likely due to the complex relationship between reproductive, biological, and sociodemographic factors, as well as to study limitations. Elucidating the role of hormonal factors should provide clues for therapeutic options and public health decisions. We provide an overview of the available evidence on reproductive factors in NHL etiology, underscoring potential sources of discrepancies and bias. PMID- 25132166 TI - Diffusion-weighted MR imaging of the rectum: clinical applications. AB - Dramatic advances in image quality over the past few years have made diffusion weighted magnetic resonance imaging (DW-MRI) a promising tool for rectal lesion evaluation. DW-MRI derives its image contrast from differences in the motion of water molecules between tissues. Such imaging can be performed quickly without the need for the administration of exogenous contrast medium. The technique yields qualitative and quantitative information that reflects changes at a cellular level and provides information about tumor cellularity and the integrity of cell membranes. The sensitivity to diffusion is obtained by applying two bipolar diffusion-sensitizing gradients to a standard T2-weighted spin echo sequence. The diffusion-sensitivity can be varied by adjusting the "b-factor", which represents the gradient duration, gradient amplitude and the time interval between the two gradients. The higher the b-value, the greater the signal attenuation from moving water protons. In this review, technical considerations relatively to image acquisition and to quantification methods applied to rectal DW-MRI are discussed. The current clinical applications of DW-MRI, either in the field of inflammatory or neoplastic rectal disease are reviewed. Also, limitations, mainly in terms of persistent lack of standardization or evaluation of tumoral response, and future directions of rectal DW-MRI are discussed. The potential utility of DW-MRI for the evaluation of rectal tumor response is on its way to being admitted but future well-designed and multicenter studies, as well as standardization of DW-MRI, are still required before a consensus can be reached upon how and when to use DW-MRI. PMID- 25132167 TI - Challenges and solutions for joining polymer materials. AB - The different mechanisms contributing to adhesion between two polymer surfaces are summarized and described in individual examples, which represent either seminal works in the field of adhesion science or novel approaches to achieve polymer-polymer adhesion. A further objective of this article is the development of new methodologies to achieve strong adhesion between low surface energy polymers. PMID- 25132168 TI - Clinical use of computed tomography and surface markers to assist internal fixation within the equine hoof. AB - OBJECTIVE: To describe clinical use of computed tomography (CT) and hoof surface markers to facilitate internal fixation within the confines of the hoof wall. STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n = 16) that had CT guided internal fixation of the distal phalanx (DP) or distal sesamoid bone (DSB). METHODS: Drill bit entry point and direction were planned from CT image series performed on hooves with grids of barium paste dots at proposed entry and projected exit sites. Post-implantation CT images were obtained to check screw position and length as well as fracture reduction. Imaging, reduction, and surgical and general anesthesia times were evaluated. Outcome was recorded. RESULTS: Screw position and length were considered near optimal in all horses, with no consequential malposition of bits or screws. Fracture reduction was evident in all cases. Preoperative planning times (at least 2 CT image acquisitions and grid creation) ranged from 10 to 20 minutes. Surgery time ranged from 45 to 90 minutes (mean, 61 minutes) and general anesthesia time ranged from 115 to 220 minutes (mean, 171 minutes). CONCLUSIONS: The combination of CT and surface marker grids allowed accurate positioning of screws in clinical DP and DSB fractures. The technique was simple and rapid. An aiming device is useful for the technique. PMID- 25132169 TI - Surgical management of well-differentiated thyroid carcinoma in children and adolescents: 33 years of experience of a single institution in Serbia. AB - Well-differentiated thyroid carcinoma in children and adolescents is rare but demonstrates aggressive behavior. Gross lymph node metastases and distant metastases are common upon first clinical presentation. During a 33-year period (1981-2014) at the Institute of Oncology and Radiology of Serbia, 62 children and adolescents underwent surgery due to well-differentiated thyroid carcinoma. Mean age was 16.7 (range 7-21) years. At the time of diagnosis 6% of patients had lung metastases. Total thyroidectomy or completion thyroidectomy was performed for all patients followed by central neck dissection and frozen section examination of jugular-carotid compartments. Median follow-up was 10.9 (range 0.69-33.05) years and median tumor size was 20 (range 2-60) mm. Papillary carcinoma was found in 96%, and follicular and Hurthle cell carcinoma in 2% of patients. Multifocal tumors were found in 50% and capsular invasion in 60% of patients. Lymphonodal metastases in either central or lateral neck compartments were found in 73% of patients. Multifocality and capsular invasion were significantly more frequent in patients less than 16 years of age (both p < 0.01). Median disease-free interval had not been reached and overall survival rate was 100%. Well-differentiated thyroid carcinoma in children and adolescents is characterized by a high rate of loco-regional aggressiveness, multifocality, capsular invasion, lymph node metastases and distant metastases at the time of diagnosis. Adequate surgical approaches should be performed for both primary and recurrent disease in young patients with well-differentiated thyroid carcinoma in order to achieve loco regional disease control and longer disease-free survival. PMID- 25132170 TI - Association of osteoporosis susceptibility genes with bone mineral density and bone metabolism related markers in Koreans: the Chungju Metabolic Disease Cohort (CMC) study. AB - In this study, we evaluated the association between bone mineral density (BMD) and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis susceptibility genes that were previously identified in genome-wide association studies (GWASs). A total of 494 men and 493 postmenopausal women participating in the Chungju Metabolic Disease cohort study in Korea were included. The following 10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESR1 rs2941740, TNFRSF11B rs3134070, TNFRSF11B rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11 rs227438, TNFSF11 rs9594782, and FOXL1 rs10048146; and the association between these SNPs and bone metabolism-related markers was assessed. Two SNPs, TNFSF11 rs2277438 and FOXL1 rs1004816, were associated with lumbar spine BMD. TNFSF11 rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594, and LRP5 rs599083 showed significant associations with femur neck BMD. These three SNPs in men and MEF2C rs1366594 and ESR1 rs2941740 in postmenopausal women were associated with femur neck BMD. A significant association between MEF2C rs1366594 and serum calcium levels was observed in men. Serum phosphorus levels were related to SOX6 rs7117858. Serum PTH levels were significantly associated with TNFRSF11B rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In conclusion, our study independently confirmed associations between several SNPs: ZBTB40, MEF2C, ESR1, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in the Korean population. PMID- 25132171 TI - Thyroid storm induced by TSH-secreting pituitary adenoma: a case report. AB - Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon tumors of the anterior pituitary gland. Patients with TSHomas may present with hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year old woman. Preoperatively she had symptoms of excessive sweating and palpitation. Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 MU U/mL, fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a pituitary tumor with maximum diameter of 13 mm that was extirpated through transsphenoidal route. After operation the patient was stuporous and thyroid storm occurred presenting with hyperthermia, hypertension, and tachycardia. It was well managed with nicardipine, midazolam, steroids, and potassium iodide. Immunohistochemical staining of tumor specimen was positive for TSH and growth hormone (GH). One year after operation, fT3 and fT4 levels were still high. As her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection therapy was started, which normalized thyroid hormone levels. This is the second reported case with thyroid storm due to TSHoma and emphasizes the importance of strategies with interdisciplinary cooperation for prevention of such emergency conditions. PMID- 25132172 TI - Reconstitution of a minimal ribosome-associated ubiquitination pathway with purified factors. AB - Ribosomes stalled on aberrant mRNAs engage quality control mechanisms that degrade the partially translated nascent polypeptide. Ubiquitination of the nascent protein is mediated by the E3 ligase Listerin via a mechanism involving ribosome subunit dissociation. Here, we reconstitute ribosome-associated ubiquitination with purified factors to define the minimal components and essential steps in this process. We find that the primary role of the ribosome splitting factors Hbs1, Pelota, and ABCE1 is to permit Listerin access to the nascent chain. Listerin alone can discriminate 60S- from 80S-nascent chain complexes to selectively ubiquitinate the former. Splitting factors can be bypassed by artificially removing the 40S subunit, suggesting that mere steric hindrance impedes Listerin recruitment. This was illustrated by a cryo-EM reconstruction of the 60S-Listerin complex that identifies a binding interface that clashes with the 40S ribosomal subunit. These results reveal the mechanistic logic of the core steps in a ribosome-associated quality control pathway. PMID- 25132173 TI - NuA4 initiates dynamic histone H4 acetylation to promote high-fidelity sister chromatid recombination at postreplication gaps. AB - CAG/CTG trinucleotide repeats are unstable, fragile sequences that strongly position nucleosomes, but little is known about chromatin modifications required to prevent genomic instability at these or other structure-forming sequences. We discovered that regulated histone H4 acetylation is required to maintain CAG repeat stability and promote gap-induced sister chromatid recombination. CAG expansions in the absence of H4 HATs NuA4 and Hat1 and HDACs Sir2, Hos2, and Hst1 depended on Rad52, Rad57, and Rad5 and were therefore arising through homology mediated postreplication repair (PRR) events. H4K12 and H4K16 acetylation were required to prevent Rad5-dependent CAG repeat expansions, and H4K16 acetylation was enriched at CAG repeats during S phase. Genetic experiments placed the RSC chromatin remodeler in the same PRR pathway, and Rsc2 recruitment was coincident with H4K16 acetylation. Here we have utilized a repetitive DNA sequence that induces endogenous DNA damage to identify histone modifications that regulate recombination efficiency and fidelity during postreplication gap repair. PMID- 25132174 TI - Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type specific master transcription factors. AB - Cell type-specific master transcription factors (TFs) play vital roles in defining cell identity and function. However, the roles ubiquitous factors play in the specification of cell identity remain underappreciated. Here we show that the ubiquitous CCAAT-binding NF-Y complex is required for the maintenance of embryonic stem cell (ESC) identity and is an essential component of the core pluripotency network. Genome-wide studies in ESCs and neurons reveal that NF-Y regulates not only genes with housekeeping functions through cell type-invariant promoter-proximal binding, but also genes required for cell identity by binding to cell type-specific enhancers with master TFs. Mechanistically, NF-Y's distinct DNA-binding mode promotes master/pioneer TF binding at enhancers by facilitating a permissive chromatin conformation. Our studies unearth a conceptually unique function for histone-fold domain (HFD) protein NF-Y in promoting chromatin accessibility and suggest that other HFD proteins with analogous structural and DNA-binding properties may function in similar ways. PMID- 25132175 TI - Genome-wide Hi-C analyses in wild-type and mutants reveal high-resolution chromatin interactions in Arabidopsis. AB - Chromosomes form 3D structures that are critical to the regulation of cellular and genetic processes. Here, we present a study of global chromatin interaction patterns in Arabidopsis thaliana. Our genome-wide approach confirmed interactions that were previously observed by other methods as well as uncovered long-range interactions such as those among small heterochromatic regions embedded in euchromatic arms. We also found that interactions are correlated with various epigenetic marks that are localized in active or silenced chromatin. Arabidopsis chromosomes do not contain large local interactive domains that resemble the topological domains described in animals but, instead, contain relatively small interactive regions scattered around the genome that contain H3K27me3 or H3K9me2. We generated interaction maps in mutants that are defective in specific epigenetic pathways and found altered interaction patterns that correlate with changes in the epigenome. These analyses provide further insights into molecular mechanisms of epigenetic regulation of the genome. PMID- 25132176 TI - Hi-C analysis in Arabidopsis identifies the KNOT, a structure with similarities to the flamenco locus of Drosophila. AB - Chromosomes are folded, spatially organized, and regulated by epigenetic marks. How chromosomal architecture is connected to the epigenome is not well understood. We show that chromosomal architecture of Arabidopsis is tightly linked to the epigenetic state. Furthermore, we show how physical constraints, such as nuclear size, correlate with the folding principles of chromatin. We also describe a nuclear structure, termed KNOT, in which genomic regions of all five Arabidopsis chromosomes interact. These KNOT ENGAGED ELEMENT (KEE) regions represent heterochromatic islands within euchromatin. Similar to PIWI-interacting RNA clusters, such as flamenco in Drosophila, KEEs represent preferred landing sites for transposable elements, which may be part of a transposon defense mechanism in the Arabidopsis nucleus. PMID- 25132177 TI - Structures of CRISPR Cas3 offer mechanistic insights into Cascade-activated DNA unwinding and degradation. AB - CRISPR drives prokaryotic adaptation to invasive nucleic acids such as phages and plasmids, using an RNA-mediated interference mechanism. Interference in type I CRISPR-Cas systems requires a targeting Cascade complex and a degradation machine, Cas3, which contains both nuclease and helicase activities. Here we report the crystal structures of Thermobifida fusca Cas3 bound to single-stranded (ss) DNA substrate and show that it is an obligate 3'-to-5' ssDNase that preferentially accepts substrate directly from the helicase moiety. Conserved residues in the HD-type nuclease coordinate two irons for ssDNA cleavage. We demonstrate ATP coordination and conformational flexibility of the SF2-type helicase domain. Cas3 is specifically guided toward Cascade-bound target DNA by a PAM sequence, through physical interactions with both the nontarget substrate strand and the CasA protein. The sequence of recognition events ensures well controlled DNA targeting and degradation of foreign DNA by Cascade and Cas3. PMID- 25132178 TI - RBFOX and SUP-12 sandwich a G base to cooperatively regulate tissue-specific splicing. AB - Tissue-specific alternative pre-mRNA splicing is often cooperatively regulated by multiple splicing factors, but the structural basis of cooperative RNA recognition is poorly understood. In Caenorhabditis elegans, ligand binding specificity of fibroblast growth factor receptors (FGFRs) is determined by mutually exclusive alternative splicing of the sole FGFR gene, egl-15. Here we determined the solution structure of a ternary complex of the RNA-recognition motif (RRM) domains from the RBFOX protein ASD-1, SUP-12 and their target RNA from egl-15. The two RRM domains cooperatively interact with the RNA by sandwiching a G base to form the stable complex. Multichromatic fluorescence splicing reporters confirmed the requirement of the G and the juxtaposition of the respective cis elements for effective splicing regulation in vivo. Moreover, we identified a new target for the heterologous complex through an element search, confirming the functional significance of the intermolecular coordination. PMID- 25132179 TI - A proton wire to couple aminoacyl-tRNA accommodation and peptide-bond formation on the ribosome. AB - During peptide-bond formation on the ribosome, the alpha-amine of an aminoacyl tRNA attacks the ester carbonyl carbon of a peptidyl-tRNA to yield a peptide lengthened by one amino acid. Although the ribosome's contribution to catalysis is predominantly entropic, the lack of high-resolution structural data for the complete active site in complex with full-length ligands has made it difficult to assess how the ribosome might influence the pathway of the reaction. Here, we present crystal structures of preattack and postcatalysis complexes of the Thermus thermophilus 70S ribosome at ~2.6-A resolution. These structures reveal a network of hydrogen bonds along which proton transfer could take place to ensure the concerted, rate-limiting formation of a tetrahedral intermediate. We propose that, unlike earlier models, the ribosome and the A-site tRNA facilitate the deprotonation of the nucleophile through the activation of a water molecule. PMID- 25132182 TI - Travelling with medications and medical equipment across international borders. AB - The international traveller needs to plan ahead to ensure medicines are available and used as directed for optimal therapeutic outcome. The planning needs to take account of legal and customs requirements for travelling with medicines for personal use. The standard advice by travel health providers is that travellers should check with the country of destination for requirements when travelling into the country with medicines for personal use. This is akin to introducing a barrier to care for this category of travellers. Innovative method of care for this group of traveller is needed. PMID- 25132180 TI - Architecture of the Saccharomyces cerevisiae RNA polymerase I Core Factor complex. AB - Core Factor (CF) is a conserved RNA polymerase (Pol) I general transcription factor comprising Rrn6, Rrn11 and the TFIIB-related subunit Rrn7. CF binds TATA binding protein (TBP), Pol I and the regulatory factors Rrn3 and upstream activation factor. We used chemical cross-linking-MS to determine the molecular architecture of CF and its interactions with TBP. The CF subunits assemble through an interconnected network of interactions between five structural domains that are conserved in orthologous subunits of the human Pol I factor SL1. We validated the cross-linking-derived model through a series of genetic and biochemical assays. Our combined results show the architecture of CF and the functions of the CF subunits in assembly of the complex. We extend these findings to model how CF assembles into the Pol I preinitiation complex, providing new insight into the roles of CF, TBP and Rrn3. PMID- 25132181 TI - Repetitive sequences in plant nuclear DNA: types, distribution, evolution and function. AB - Repetitive DNA sequences are a major component of eukaryotic genomes and may account for up to 90% of the genome size. They can be divided into minisatellite, microsatellite and satellite sequences. Satellite DNA sequences are considered to be a fast-evolving component of eukaryotic genomes, comprising tandemly-arrayed, highly-repetitive and highly-conserved monomer sequences. The monomer unit of satellite DNA is 150-400 base pairs (bp) in length. Repetitive sequences may be species- or genus-specific, and may be centromeric or subtelomeric in nature. They exhibit cohesive and concerted evolution caused by molecular drive, leading to high sequence homogeneity. Repetitive sequences accumulate variations in sequence and copy number during evolution, hence they are important tools for taxonomic and phylogenetic studies, and are known as "tuning knobs" in the evolution. Therefore, knowledge of repetitive sequences assists our understanding of the organization, evolution and behavior of eukaryotic genomes. Repetitive sequences have cytoplasmic, cellular and developmental effects and play a role in chromosomal recombination. In the post-genomics era, with the introduction of next-generation sequencing technology, it is possible to evaluate complex genomes for analyzing repetitive sequences and deciphering the yet unknown functional potential of repetitive sequences. PMID- 25132183 TI - Molecular characterization of oxytocin receptor gene in water buffalo (Bubalus bubalis). AB - Buffaloes are known for their productivity as compared to average yielding cows due to higher fat percentage, better feed conversion ability and disease resistance. On the other hand, the reproductive performances of buffaloes are often considered as poor owing to late sexual maturity, weak/silent oestrus, repeat breeder and prolonged intercalving interval. The study of cascade of events during oestrus and oestrous cycle can be useful for the improvement of reproductive efficiency of buffaloes. More precisely, the hormonal changes initiated at the molecular level within the animal determine the reproductive nature of the species. Nucleotide/protein sequence analysis serves as a vital tool in analysing the binding of the hormones for their effect or functions. In this study, we have reported cloning and characterization of the complete coding (cDNA) sequence of oxytocin receptor gene (OXTR) in buffaloes. Buffalo OXTR gene contains an uninterrupted ORF of 1176 nucleotides corresponding to an inferred polypeptide length of 391 amino acids (aa). The molecular weight of the deduced aa sequence was found to be 43 kDa with an isoelectric point of 9.253 and 16.328 charge at pH 7.0. The deduced protein sequence consists of 38 strongly basic (+) (K,R), 22 strongly acidic (-) (D,E), 186 hydrophobic (A, I, L, F, W, V) and 95 Polar (N, C, Q, S, T, Y) aa. Results indicated that aspartate (D) at aa position 85 and D, R and C at aa positions 136, 137 and 138, respectively, are conserved in buffaloes. The buffalo OXTR gene shared a per cent similarity ranging from 84.7 to 98.1 and 88.5 to 97.7 at nucleotide and deduced aa sequence levels, respectively, with that of other species. Phylogram constructed on the basis of either nucleotide or deduced aa sequences of buffalo OXTR gene showed that buffalo, cattle and sheep have diverged from human and swine and formed a separate clad. The buffalo sequence has shown maximum similarity and closeness with cattle followed by sheep both at nucleotide and at aa level. PMID- 25132184 TI - Theoretical study on molecular structure and vibrational analysis included FT-IR, FT-Raman and UV techniques of 2,4,5-trimethylbenzoic acid (monomer and dimer structures). AB - Theoretical study on the structural and vibrational analysis of monomer and dimer structures of 2,4,5-trimethylbenzoic acid (2,4,5-TMBA, C10H12O2) were presented. The geometry of the molecule was fully optimized. The Fourier transform infrared (FT-IR) and the Fourier transform Raman (FT-Raman) spectra of the title molecule in solid phase were recorded in the region 4000-400 cm(-1) and 4000-50 cm(-1), respectively. The geometrical parameters and energies were investigated with the help of Density Functional Theory (DFT) employing B3LYP method and 6-311++G(d,p) basis set. The spectroscopic data of the molecule in the ground state were calculated by using DFT/B3LYP method with the 6-311++G(d,p) basis set. The vibrational spectra were calculated and fundamental vibrations were assigned on the basis of the potential energy distribution (PED) of the vibrational modes. The geometric parameters were compared with experimental data of the title molecule. The UV absorption spectrum of the studied compound was computed and recorded in the range of 190-400 nm dissolved in water and ethanol. Besides, charge transfer occurring in the molecule between HOMO and LUMO energies, frontier energy gap, molecular electrostatic potential (MEP) were calculated and presented. In addition these, thermodynamic properties and Mulliken atomic charges were performed. PMID- 25132185 TI - Common ENT disorders in pediatrics. PMID- 25132187 TI - Is surgical removal of the noncompacted layer the clue to treat left ventricular hypertrabeculation/noncompaction? PMID- 25132186 TI - Dumping syndrome with severe hipoglycemia after Nissen fundoplication in adults. Case report and literature review. PMID- 25132188 TI - Exercise tolerance in obese vs. lean adolescents: a systematic review and meta analysis. AB - To prescribe feasible and medically safe exercise interventions for obese adolescents, it remains to be determined whether exercise tolerance is altered and whether anomalous cardiopulmonary responses during maximal exercise testing are present. Studies that examined cardiopulmonary responses to maximal exercise testing in obese adolescents were searched: cardiopulmonary exercise tests with respiratory gas exchange measurements of peak oxygen uptake (VO2peak) were performed and comparisons between obese and lean adolescents were made. Study quality was assessed using a standardized item list. By meta-analyses VO2peak, peak cycling power output (Wpeak) and peak heart rate (HRpeak) were compared between groups. Nine articles were selected (333 obese vs. 145 lean adolescents). VO2peak (L min(-1)), HRpeak and Wpeak were not different between groups (P >= 0.10), while a trend was found for a reduced VO2peak (mL min(-1) kg(-1) lean tissue mass) (P=0.07) in obese vs. lean adolescents. It remained uncertain whether anomalous cardiopulmonary responses occur during maximal exercise testing in obese adolescents. In conclusion, a trend was found for lowered VO2peak (mL min(-1)kg(-1) lean tissue mass) in obese vs. lean adolescents. Whether cardiopulmonary anomalies during maximal exercise testing would occur in obese adolescents remains uncertain. Studies are therefore warranted to examine the cardiopulmonary response during maximal exercise testing in obese adolescents. PMID- 25132189 TI - iPSC Transplantation increases regeneration and functional recovery after ischemic stroke in neonatal rats. AB - Limited treatments are available for perinatal/neonatal stroke. Induced pluripotent stem cells (iPSCs) hold therapeutic promise for stroke treatment, but the benefits of iPSC transplantation in neonates are relatively unknown. We hypothesized that transplanted iPSC-derived neural progenitor cells (iPSC-NPCs) would increase regeneration after stroke. Mouse pluripotent iPSCs were differentiated into neural progenitors using a retinoic acid protocol. Differentiated neural cells were characterized by using multiple criteria and assessments. Ischemic stroke was induced in postnatal day 7 (P7) rats by occluding the right middle cerebral artery and right common carotid artery. iPSC NPCs (400,000 in 4 ul) were transplanted into the penumbra via intracranial injection 7 days after stroke. Trophic factor expression in the peri-infarct tissue was measured using Western blot analysis. Animals received daily bromodeoxyuridine (BrdU) injections and were sacrificed 21 days after stroke for immunohistochemistry. The vibrissae-elicited forelimb placement test was used to evaluate functional recovery. Differentiated iPSCs expressed mature neuronal markers, functional sodium and potassium channels, and fired action potentials. Several angiogenic and neurogenic trophic factors were identified in iPSC-NPCs. Animals that received iPSC-NPC transplantation had greater expression of stromal cell-derived factor 1-alpha (SDF-1alpha) and vascular endothelial growth factor (VEGF) in the peri-infarct region. iPSC-NPCs stained positive for neuronal nuclei (NeuN) or glial fibrillary acidic protein (GFAP) 14 days after transplantation. iPSC-NPC-transplanted animals showed greater numbers of BrdU/NeuN and BrdU/Collagen IV colabeled cells in the peri-infarct area compared with stroke controls and performed better in a sensorimotor functional test after stroke. iPSC-NPC therapy may play multiple therapeutic roles after stroke by providing trophic factors, increasing angiogenesis and neurogenesis, and providing new cells for tissue repair. PMID- 25132190 TI - A novel treatment for propagated crown fractures. AB - INTRODUCTION: A major complication after endodontic treatment is persistent pain on biting or chewing. Although unsuccessful endodontic treatment can account for such pain, pain to chewing and biting can also be a result of an unsupported or propagated crown fracture. Crown fractures that extend apically result in deterioration of the localized periodontium and ultimate loss of the tooth. To date, no predictable treatment for apically extending crown fractures exists. METHODS: Three cases of nonsurgical excision of a propagated crown fracture and the repair of the subsequent iatrogenic perforation are presented. RESULTS/CONCLUSIONS: This case report series describes a novel treatment for apically progressive crown fractures that results in patient comfort and maintenance as well as improved periodontal status of the tooth. PMID- 25132191 TI - Automated Competitive Protein-Binding Assay for Total 25-OH Vitamin D, Multicenter Evaluation and Practical Performance. AB - BACKGROUND: The Roche Elecsys Vitamin D Total competitive protein-binding assay uses recombinant vitamin D binding protein for measuring 25-hydroxyvitamin D (25 OHD), which is different from commonly used antibody assays. METHODS: The assay, standardized against LC-MS/MS, was tested at four sites. Evaluation included precision; between-laboratory variability; functional sensitivity; correlation to LC-MS/MS, HPLC, and immunoassays; as well as robustness, traceability, and EQAS performance. RESULTS: Precision testing showed within-run coefficient of variations (CVs) of <= 7%, within-laboratory CVs of <9.5%, between-laboratory precision CVs of <= 10.1%, and a functional sensitivity below 9.8 nmol/l (at CV 12.9%). The assay showed equivalent 25-OHD levels for matched serum and plasma samples, good reagent lot-to-lot consistency in pooled sera over time, and good agreement with HPLC (relative bias -8.8%). Comparison with LC-MS/MS methods yielded relative biases of -15.4, -13.5, -10.2, and 3.2%. Comparison against immunoassays showed a relative bias of 14.5% (DiaSorin Liaison) and -58.2% (IDS iSYS). The overall mean results in 2 years DEQAS was 102% of the ALTM. In a certified reference patient panel, the average bias was < 4% for the sum of 25 OHD2 and 25-OHD3. CONCLUSION: The Elecsys Vitamin D Total assay demonstrated good overall performance and is, according to present standards, very suitable for automated measurement of 25-OHD. PMID- 25132192 TI - Recovery of the response to biological treatments using narrow band ultraviolet-B in patients with moderate to severe psoriasis: a retrospective study of 17 patients. AB - BACKGROUND/PURPOSE: Biological therapy has demonstrated a very satisfactory anti psoriatic effect; however, the loss of response with time has been reported. OBJECTIVE: To evaluate the efficacy of the narrow band ultraviolet-B phototherapy (NB-UVB) as a rescue in patients with moderate to severe psoriasis who have lost efficacy in their biological treatment. METHODS: A retrospective chart review study was conducted on patients with moderate to severe psoriasis receiving treatment with a biologic, with a good initial response that subsequently had lost efficacy. All the patients received combined treatment with NB-UVB. RESULTS: Seventeen patients were included, with a mean age of 44 years. The biologics were: 8 etanercept, 4 adalimumab, 3 ustekinumab, 1 efalizumab, and 1 infliximab. The mean NB-UVB sessions was 25 (7-48 sessions), with a mean accumulated dose of 31.12 J/cm(2) (5.2-94.6 J/cm(2) ). Sixteen patients had the following results: 44% PASI 90-100, 31.3% PASI 75-89, and 25% PASI 50-74 response. CONCLUSION: According to this study on clinical practice, it could be considered that the use of NB-UVB along with biological drugs that have lost efficacy in controlling moderate to severe psoriasis in adults could contribute to the recovery of the initial response. PMID- 25132193 TI - Paired box 2 upregulates androgen receptor gene expression in androgen independent prostate cancer. AB - Androgen-independent prostate cancer is known as a hormone-refractory disease. Although the androgen receptor (AR) is considered to be a key regulator of androgen-independent prostate cancer progression, the mechanism through which AR gene expression is regulated is not well understood. In the present study, we showed that the AR gene was upregulated by paired box 2 (PAX2) in androgen independent prostate cancer. When PAX2 upregulated AR gene expression, a decrease in DNA methylation of the AR gene locus was also observed. PAX2 was highly expressed and promoted cell growth in an androgen-independent prostate cancer cell line (22Rv1). The cell growth inhibition by PAX2 knockdown was rescued by AR overexpression in 22Rv1 cells. In a mouse xenograft model of androgen-independent prostate cancer, PAX2 knockdown inhibited tumor growth and AR gene expression and also increased DNA methylation of the AR gene. Consistent with this, AR and PAX2 expression levels were positively correlated in prostate cancer patients. These findings suggested that PAX2 promoted cancer cell growth in androgen-independent prostate cancer by regulating AR gene expression through an epigenetic mechanism. PMID- 25132194 TI - Twenty-four-hour intraocular pressure patterns in patients with thyroid eye disease. AB - BACKGROUND: To prospectively investigate the safety, tolerability and 24-h intraocular pressure (IOP) patterns in patients with thyroid eye disease (TED) using a contact lens sensor (CLS). DESIGN: Prospective study. PARTICIPANTS: Ten patients with established TED. METHODS: Ten eyes of 10 patients were prospectively evaluated in an ambulatory 24-h IOP monitoring session using the CLS (Sensimed AG, Lausanne, Switzerland). Patients pursued daily activities, and sleep behaviour was uncontrolled. MAIN OUTCOME MEASURES: Incidence of adverse events (AEs) and tolerability (scale of 0-10, increasing intolerance) were assessed. IOP patterns were evaluated using a cosinor rhythmometry model, and linear regression slopes were constructed for the transition from wake/sitting (W/S) to sleep/supine (S/S) and vice versa. RESULTS: Mean age was 61.8 +/- 21.6 years, and 90% of patients were female. Main AEs were blurred vision (50%), conjunctival hyperaemia (100%) and superficial punctate keratitis (20%). Tolerability of the lens was found to be 1.5 +/- 0.7. Positive linear slopes of the CLS signal from wake to sleep were detected (18.0 +/- 43.8 arbitrary units [a.u.]; P = 0.254), whereas at the transition from S/S to W/S a significant decrease (-62.9 +/- 56.8 a.u.; P = 0.010) was found. Five patients (50%) had a significant nocturnal/sleep acrophase with the peak occurring at 6:30 a.m. The mean amplitude of the 24-h curves was 102.2 +/- 52.6 a.u. CONCLUSIONS: In patients with TED, the CLS provides a safe and well-tolerated approach to 24-h IOP monitoring. After modelling the 24-h IOP curves, TED patients were found to have a morning acrophase. PMID- 25132195 TI - Size-dependent thermochromism through enhanced electron-phonon coupling in 1 nm quantum dots. AB - 1 nm CuO quantum dots (QDs) were produced in size-controlled super-micropores of a silica matrix. The reversible color change of the QDs from pale blue to deep green was clearly observed in a wide temperature range from 298 to 673 K. This particular thermochromism is ascribed to an enhanced bandgap shift depending on temperature with a strong electron-phonon coupling in the confined space of the 1 nm QDs. PMID- 25132196 TI - Paleontology and evolution-part II. PMID- 25132197 TI - Bachmann's bundle and coronary sinus ostial pacing accentuate left atrial electrical dyssynchrony in an acute canine model. AB - INTRODUCTION: In patients with intraatrial conduction delay and sinus node (SN) dysfunction, pacing Bachmann's bundle (BBR) and coronary sinus ostium (CSO) has been suggested to achieve atrial resynchronization with potential beneficial impact on atrial fibrillation and diastolic heart failure. Clinical studies have not shown superiority of one approach. METHODS AND RESULTS: We studied electrical activation sequence in an open-chest acute canine model of normal atrial function in 8 mongrel dogs under general anesthesia. Bipolar plunge electrodes were distributed over the surface of the atria during unifocal pacing, and intracardiac activation sequence was observed. SN pacing resulted in near simultaneous activation at midline sites (BBR and CSO); the left atrium (LA) was activated by anterior and posterior wavefronts simultaneously propagating septally to laterally and meeting at the low-lateral perimitral LA. Right atrial appendage (RAA) pacing created intra-RA conduction delay and delayed onset of LA activation. Pacing from RAA, CSO, and BBR resulted in nonsimultaneous activation at midline sites and produced an anteroposterior gradient of LA activation. This phenomenon was seen to the greatest degree with midline pacing and shifted the site of latest activation away from the low-lateral perimitral LA in all pacing configurations except SN pacing. CONCLUSION: Pacing-induced intra-LA activation dispersion is enhanced with midline atrial pacing, and secondarily shifts the site of latest activation away from the lateral mitral annulus. Measuring atrial activation times to the low-lateral perimitral LA can underestimate the degree of atrial dyssynchrony and be misinterpreted as atrial synchrony. Establishing clinical impact requires evaluation of human data. PMID- 25132198 TI - Onychomadesis: literature review. AB - Onychomadesis is characterized by separation of the nail plate from the matrix with persistent attachment to the nail bed and often, but not always, eventual shedding. Onychomadesis has been associated with infection, autoimmune disease, critical illness and medications. To our knowledge a literature review of all associations with onychomadesis has not been completed previously. Most commonly, onychomadesis has been reported in association with pemphigus vulgaris and hand foot-mouth disease, and following chemotherapy or antiepileptic medications. This article summarizes these key culprit associations, postulates the pathogenesis of nail matrix arrest and summarizes the clinical outcomes. We conducted a retrospective review of cases of onychomadesis reported from January 1960 to March 2013. Using the PubMed database, the literature was searched using the following terms: 'onychomadesis' and 'proximal nail shedding'. Also, an Ovid search was carried out using the same terms. In total 56 articles have been published, including our previously reported series of idiopathic onychomadesis. Articles pertaining only to Beau's lines and not true onychomadesis were excluded. Onychomadesis has been associated with autoimmune disease, other major medical illness, neonatal illness, medication and infection. PMID- 25132199 TI - Comparing the trends of elevated blood pressure in appalachian and non Appalachian regions. AB - As an established risk factor for cardiovascular disease and stroke, hypertension risks are often thought to be more prevalent in Appalachian mountain ranges when compared with other neighboring counterpart regions. This study evaluated blood pressure (BP) readings among 2358 Kentucky residents attending community stroke risk screening events held in 15 counties, including nine Appalachian counties (n=1134) and six non-Appalachian counties (n=1224). With high BP being operationally defined as >=140/90 mm Hg, 41.5% of Appalachian county residents had elevated BP compared with 42.6% among those from non-Appalachian counties. Although the counties with the highest rates of elevated BP did tend to reside in the Appalachian region, there was no significant difference between rates of elevated BP in Appalachia vs non-Appalachian counties. This dataset is proposed as a pilot project to encourage further pursuit of a larger controlled project. PMID- 25132200 TI - EEG-based monitor on anti-nociception during general anaesthesia: mission impossible? PMID- 25132201 TI - Dexmedetomidine does not reduce emergence agitation in adults following orthognathic surgery. AB - BACKGROUND: Patients undergoing orthognathic surgery are at high risk of developing emergence agitation. We hypothesised that a single-dose of dexmedetomidine would reduce emergence agitation in adults with nasotracheal intubation after orthognathic surgery. METHODS: Seventy adults (20-45 years old) undergoing orthognathic surgery were randomly assigned to two groups. Patients received intravenous dexmedetomidine 1 MUg/kg (dex group) or normal saline (control group) for 10 min at the end of surgery. Remifentanil was infused at 0.02 MUg/kg/min during emergence in both groups. The severity of emergence agitation was assessed with the Richmond agitation-sedation scale. Cough, haemodynamic and respiratory profiles, pain, and time to eye opening were evaluated. RESULTS: The incidence of emergence agitation was not different between dex group and control group (38% vs. 47%, P = 0.45). However, severe cough during emergence was reduced in the dex group (P = 0.04). Tachycardia during emergence and recovery phases was attenuated in the dex group. The verbal numeric rating of pain was lower in the dex group. There were no differences in respiratory rate between the two groups. Time to eye opening was prolonged in the dex group. CONCLUSION: The addition of a single dose of dexmedetomidine (1 MUg/kg) to low-dose remifentanil infusion did not attenuate emergence agitation in intubated patients after orthognathic surgery compared with low-dose remifentanil infusion alone. However, single-dose dexmedetomidine suppressed coughing, haemodynamic changes, and pain during emergence and recovery phases, without respiratory depression. Delayed awakening might be associated with this treatment. PMID- 25132204 TI - Photoluminescence, chemiluminescence and anodic electrochemiluminescence of hydrazide-modified graphene quantum dots. AB - Single-layer graphene quantum dots (SGQDs) were refluxed with hydrazine (N2H4) to prepare hydrazide-modified SGQDs (HM-SGQDs). Compared with SGQDs, partial oxygen containing groups have been removed from HM-SGQDs. At the same time, a lot of hydrazide groups have been introduced into HM-SGQDs. The introduced hydrazide groups provide HM-SGQDs with a new kind of surface state, and give HM-SGQDs unique photoluminescence (PL) properties such as blue-shifted PL emission and a relatively high PL quantum yield. More importantly, the hydrazide-modification made HM-SGQDs have abundant luminol-like units. Accordingly, HM-SGQDs exhibit unique and excellent chemiluminescence (CL) and anodic electrochemiluminescence (ECL). The hydrazide groups of HM-SGQDs can be chemically oxidized by the dissolved oxygen (O2) in alkaline solutions, producing a strong CL signal. The CL intensity is mainly dependent on the pH value and the concentration of O2, implying the potential applications of HM-SGQDs in pH and O2 sensors. The hydrazide groups of HM-SGQDs can also be electrochemically oxidized in alkaline solutions, producing a strong anodic ECL signal. The ECL intensity can be enhanced sensitively by hydrogen peroxide (H2O2). The enhanced ECL intensity is proportional to the concentration of H2O2 in a wide range of 3 MUM to 500 MUM. The detection limit of H2O2 was calculated to be about 0.7 MUM. The results suggest the great potential applications of HM-SGQDs in the sensors of H2O2 and bio-molecules that are able to produce H2O2 in the presence of enzymes. PMID- 25132203 TI - Risk of complications due to anticoagulation during dermatosurgical procedures: a systematic review and meta-analysis. AB - Background Management of anticoagulation and anti-platelet drugs during cutaneous surgery is still a challenge for many dermatologists and standards of care with respect to stopping, continuing or bridging vary widely. Methods We performed a systematic review (Medline, Cochrane Library, until August 27th, 2013) of studies assessing the risk of complications due to anticoagulation during cutaneous surgery. Primary outcomes were mild-moderate and severe postsurgical bleeding. The secondary outcomes were excessive and uncontrollable intraoperative bleeding and other postsurgical complications as wound dehiscence, erythema, wound infection. Results 1.287 publications were identified and 10 studies were included into the review. The frequencies of bleeding in the control groups in general were low (about 1%). In patients on aspirin, increased risks were seen neither with respect to mild-moderate postoperative bleeding (RR 1.1, CI 0.5 2.3), nor with respect to severe bleeding (RR 0.9, CI 0.2-4.6). The studies with patients on warfarin showed a risk for mild-moderate bleeding that was three times as high as in controls (RR 3.2, CI 1.4-7.1) and for severe bleeding that was 15 times higher (RR 14.8, CI 2.7-80.4). In general the study sizes were small and the methodological quality low. Conclusion The risk of bleeding due to a medication with aspirin seems to be negligible. With warfarin, the risk is increased; an exact estimate of the risk increase is difficult to give, because of the lack of sufficient high quality studies. A two-fold increase appears likely, the 15-fold increase is most likely due to statistical reasons arising from the rareness of the event in the small number of included patients. Stopping, bridging or continuing a medication should always be an individual decision. In accordance with guidelines from internal medicine for most patients it will be recommendable to continue with the medication. PMID- 25132205 TI - Simultaneous determination of phenolic compounds in Equisetum palustre L. by ultra high performance liquid chromatography with tandem mass spectrometry combined with matrix solid-phase dispersion extraction. AB - A method based on matrix solid-phase dispersion extraction followed by ultra high performance liquid chromatography with tandem mass spectrometry is presented for the extraction and determination of phenolic compounds in Equisetum palustre. This method combines the high efficiency of matrix solid-phase dispersion extraction and the rapidity, sensitivity, and accuracy of ultra high performance liquid chromatography with tandem mass spectrometry. The influential parameters of the matrix solid-phase dispersion extraction were investigated and optimized. The optimized conditions were as follows: silica gel was selected as dispersing sorbent, the ratio of silica gel to sample was selected to be 2:1 (400/200 mg), and 8 mL of 80% methanol was used as elution solvent. Furthermore, a fast and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the determination of nine phenolic compounds in E. palustre. This method was carried out within <6 min, and exhibited satisfactory linearity, precision, and recovery. Compared with ultrasound-assisted extraction, the proposed matrix solid-phase dispersion procedure possessed higher extraction efficiency, and was more convenient and time saving with reduced requirements on sample and solvent amounts. All these results suggest that the developed method represents an excellent alternative for the extraction and determination of active components in plant matrices. PMID- 25132207 TI - Use of anion gap in the evaluation of a patient with metabolic acidosis. AB - High anion gap (AG) metabolic acidosis, a common laboratory abnormality encountered in clinical practice, frequently is due to accumulation of organic acids such as lactic acid, keto acids, alcohol metabolites, and reduced kidney function. The cause of high AG metabolic acidosis often is established easily using historical and simple laboratory data. Despite this, several challenges in the diagnosis and management of high AG metabolic acidosis remain, including quantifying the increase in AG, understanding the relationship between changes in AG and serum bicarbonate level, and identifying the cause of high AG metabolic acidosis when common causes are ruled out. The present case was selected to highlight the importance of the correction of AG for serum albumin level, the use of actual baseline AG rather than mean normal AG, the relationship between changes in serum bicarbonate level and AG, and a systematic diagnostic approach to uncommon causes of high AG metabolic acidosis, such as 5-oxoproline acidosis (pyroglutamic acidosis). PMID- 25132208 TI - Biochemical cartilage alteration and unexpected signal recovery in T2* mapping observed in ankle joints with mobile MRI during a transcontinental multistage footrace over 4486 km. AB - OBJECTIVE: The effect of ultra-long distance running on the ankle cartilage with regard to biochemical changes, thickness and lesions is examined in the progress of a transcontinental ultramarathon over 4486 km. METHOD: In an observational field study, repeated follow-up scanning of 22 participants of the TransEurope FootRace (TEFR) with a 1.5 T MRI mounted on a mobile unit was performed. For quantitative biochemical and structural evaluation of cartilage a fast low angle shot (FLASH) T2* weighted gradient-echo (GRE)-, a turbo-inversion-recovery magnitude (TIRM)- and a fat-saturated proton density (PD)-weighted sequence were utilized. Statistical analysis of cartilage T2* and thickness changes was obtained on the 13 finishers (12 male, mean age 45.4 years, BMI 23.5 kg/m2). None of the nine non-finisher (eight male, mean age 53.8 years, BMI 23.4 kg/m2) stopped the race due to ankle problems. RESULTS: From a mean of 17.0 ms for tibial plafond and 18.0 ms for talar dome articular cartilage at baseline, nearly all observed regions of interest (ROIs) of the ankle joint cartilage showed a significant T2*-signal increase (25.6% in mean), with standard error ranging from 19% to 33% within the first 2500 km of the ultra-marathon. This initial signal behavior was followed by a signal decrease. This signal recovery (30.6% of initial increase) showed a large effect size. No significant morphological or cartilage thickness changes (at baseline 2.9 mm) were observed. CONCLUSION: After initial T2*-increase during the first 2000-2500 km, a subsequent T2*-decrease indicates the ability of the normal cartilage matrix to partially regenerate under ongoing multistage ultramarathon burden in the ankle joints. PMID- 25132209 TI - A systematic review of interventions to detect dementia or cognitive impairment. AB - BACKGROUND: Memory services have been implemented nationally to increase early dementia diagnosis, and further evaluation of their impact and other strategies to increase timely dementia diagnosis are needed. AIMS: To systematically review the literature for interventions intended to increase the detection of dementia or suspected dementia or people presenting with memory complaints. METHOD: We searched electronic databases, hand searched references and contacted authors of included papers, contacted field experts and UK charities and councils for data about their dementia awareness programmes. RESULTS: We included 13 studies, of which four were randomised controlled trials (RCT). Two RCTs found that general practitioner (GP) education increased suspected dementia cases. One RCT found up to six home visits from a specialist geriatric nurse over 30 months increased the rate of accurately diagnosed dementia. There was preliminary evidence from non randomised studies that memory clinics increase timely diagnosis, but no evidence they increase the overall diagnosis rate. CONCLUSIONS: There is good quality evidence that GP education increases the number of suspected dementia cases but not accurate or earlier dementia diagnoses. One RCT reported that multiple visits from a trained nurse increase the diagnosis rate. There is no cost effectiveness evidence. Our findings suggest good quality RCTs are needed to test the effectiveness and cost-effectiveness of interventions to increase dementia detection. PMID- 25132206 TI - Randomized controlled pilot study of mindfulness-based stress reduction for persistently fatigued cancer survivors. AB - OBJECTIVE: Cancer-related fatigue (CRF) is one of the most common, persistent, and disabling symptoms associated with cancer and its treatment. Evidence-based treatments that are acceptable to patients are critically needed. This study examined the efficacy of mindfulness-based stress reduction (MBSR) for CRF and related symptoms. METHOD: A sample of 35 cancer survivors with clinically significant CRF was randomly assigned to a 7-week MBSR-based intervention or wait list control group. The intervention group received training in mindfulness meditation, yoga, and self-regulatory responses to stress. Fatigue interference (primary outcome) and a variety of secondary outcomes (e.g., fatigue severity, vitality, disability, depression, anxiety, and sleep disturbance) were assessed at baseline, post-intervention, and 1-month follow-up. Bonferroni correction was employed to account for multiple comparisons. Controls received the intervention after the 1-month follow-up. Participants in both groups were followed for 6 months after completing their respective MBSR courses to assess maintenance of effects. RESULTS: Compared to controls, the MBSR group reported large post intervention reductions as assessed by effect sizes (d) in the primary outcome, fatigue interference (d = -1.43, p < 0.001), along with fatigue severity (d = 1.55, p < 0.001), vitality (d = 1.29, p < 0.001), depression (d = -1.30, p < 0.001), and sleep disturbance (d = -0.74, p = 0.001). Results were maintained or strengthened at 1-month follow-up, the point at which significant improvements in disability (d = -1.22, p < 0.002) and anxiety (d = -0.98, p = 0.002) occurred. Improvements in all outcomes were maintained 6 months after completing the course. MBSR adherence was high, with 90% attendance across groups and high rates of participant-reported home practice of mindfulness. CONCLUSIONS: Mindfulness based stress reduction is a promising treatment for CRF and associated symptoms. PMID- 25132210 TI - Evaluation of the microbial quality of fresh ejaculates of camel (Camelus dromedarius) semen. AB - A series of five factorial arranged experiments were conducted to investigate the effect of different management during semen collection on the microbial quality (bacterial load, type of microbes and frequency of isolation) of dromedaries' semen. Microbial analysis of seventy-nine fresh ejaculates from twenty-two camels showed the presence of nine variant colonies. The most prevalent organisms in the dromedary semen were species of Staphylococcus, Bacillus and Streptococcus. One yeast species was represented among the isolates. The middle aged camels (9-13 years) had significantly (P>0.05) higher mean bacterial loads than young (4-8 years) and old aged (14-18 years) animals. The mean bacterial populations of ejaculates collected by an electro-ejaculator were significantly (P>0.05) higher than those collected by an artificial vagina. Candida spp. was identified in 53.8% of the samples collected by an electro-ejaculator and was not detected in ejaculates collected by an artificial vagina. The mean semen bacterial load detected during the breeding season was significantly (P<0.01) higher than that collected during the non-breeding season. No fungi were isolated from semen samples collected in the non-breeding season. The difference between the mean semen bacterial loads in the first and the second ejaculate was highly significant (P<0.01). The preputial wash significantly (P<0.01) reduced the bacterial load. This study revealed that the microbial contamination of dromedaries' semen is found in different intensities during different management procedures of semen collection. PMID- 25132211 TI - Influence of melatonin receptor 1A gene polymorphisms on seasonal reproduction in Sarda ewes with different body condition scores and ages. AB - In several species, circadian changes in melatonin concentrations play a key role in the photoperiodic control of seasonality. In sheep, two silent mutations in the melatonin receptor 1A gene (MTNR1A) at positions 606 and 612 of the exon II are associated with seasonal reproduction. However, in some sheep breeds, no relationships have been found between MTNR1A polymorphisms and reproductive seasonality. This lack of relationship could be due to effects of breed, body condition, age, and/or environmental conditions. Thus, the present study was conducted with the Sarda sheep breed with the aim of documenting the effect of MTNR1A gene polymorphisms on reproductive resumption and to evaluate whether such this effect was modified by differences in body condition score (BCS) and age. Six hundred three- to six-year-old multiparous ewes with BCSs between 2.5 and 3.5 were selected. Genomic DNA was extracted and subjected to PCR to amplify the ovine exon II of the MTNR1A gene. The amplicons were subjected to digestion with the restriction enzymes RsaI and MnlI to detect the T606C and A612G polymorphisms, respectively. Ewes carrying the G/G, G/A, C/C, and C/T genotypes exhibited higher fertility rates (P<0.05) and fewer numbers of days between the introduction of rams and parturition (P<0.05) than did the A/A and T/T genotypes. The data revealed that the MTNR1A gene polymorphisms influenced spring reproductive resumption in the Sarda sheep breed. Moreover, the data also indicated that, over the limited ranges evaluated in this study, BCS and age had no significant influence on reproductive activity. PMID- 25132213 TI - Li-rich anti-perovskite Li3OCl films with enhanced ionic conductivity. AB - Anti-perovskite solid electrolyte films were prepared by pulsed laser deposition, and their room-temperature ionic conductivity can be improved by more than an order of magnitude in comparison with its bulk counterpart. The cyclability of Li3OCl films in contact with lithium was evaluated using a Li/Li3OCl/Li symmetric cell, showing self-stabilization during cycling test. PMID- 25132212 TI - Durability of the efficacy and safety of alogliptin compared with glipizide in type 2 diabetes mellitus: a 2-year study. AB - AIMS: To evaluate the long-term durability of the efficacy of alogliptin compared with glipizide in combination with metformin in people with type 2 diabetes inadequately controlled on stable-dose metformin. METHODS: This multicentre, double-blind, active-controlled study randomized 2639 patients aged 18-80 years to 104 weeks of treatment with metformin in addition to alogliptin 12.5 mg once daily (n = 880), alogliptin 25 mg once daily (n = 885) or glipizide 5 mg once daily, titrated to a maximum of 20 mg (n = 874). The primary endpoint was least square mean change from baseline in HbA1c level at 104 weeks. RESULTS: The mean patient age was 55.4 years, the mean diabetes duration was 5.5 years and the mean baseline HbA1c was 7.6%. HbA1c reductions at week 104 were -0.68%, -0.72% and 0.59% for alogliptin 12.5 and 25 mg and glipizide, respectively [both doses met the criteria for non-inferiority to glipizide (p<0.001); alogliptin 25 mg met superiority criteria (p=0.010)]. Fasting plasma glucose concentration decreased by 0.05 and 0.18 mmol/l for alogliptin 12.5 and 25 mg, respectively, and increased by 0.30 mmol/l for glipizide (p < 0.001 for both comparisons with glipizide). Mean weight changes were -0.68, -0.89 and 0.95 kg for alogliptin 12.5 and 25 mg and glipizide, respectively (p < 0.001 for both comparisons with glipizide). Hypoglycaemia occurred in 23.2% of patients in the glipizide group vs. 2.5 and 1.4% of patients in the alogliptin 12.5 and 25 mg groups, respectively. Pancreatitis occurred in one patient in the alogliptin 25 mg group and three in the glipizide group. CONCLUSIONS: Alogliptin efficacy was sustained over 2 years in patients with inadequate glycaemic control on metformin alone. PMID- 25132214 TI - Characterizing genetic variation of adrenergic signalling pathways in Takotsubo (stress) cardiomyopathy exomes. AB - AIMS: Exome sequencing was used to genotype comprehensively a Takotsubo (stress) cardiomyopathy (TC) cohort, enabling investigation of a vast 486 gene network for adrenergic signalling. METHODS AND RESULTS: Twenty-eight TC subjects, including a mother-daughter pair and five recurrent cases, underwent whole-exome sequencing. Frequencies of 17 common, functional adrenergic polymorphisms were statistically similar to those of population controls. Filtering for rare, predicted deleterious, catecholamine/adrenergic signalling variants revealed heterozygosity in 55 genes in TC cases and 59 genes in healthy controls. Overall allele burden was similar and did not discriminate clinical variables among TC subjects, but gene identities were largely cohort specific, and TC cases were enriched for variants within functional domains (68% vs. 48%, P = 0.031). Two-thirds of TC cases carried more than one filtered adrenergic pathway variant, and 11 genes harboured a variant in >= 2 cases. The mother-daughter pair shared missense variants in highly conserved functional domains of ADH5, CACNG1, EPHA4, and PRKCA. An adrenergic pathway-independent analysis of the cohort exposed no common gene for TC. CONCLUSIONS: Overall, these data support genetic heterogeneity in TC susceptibility and a likely polygenic basis, conferring a cumulative effect on adrenergic pathway dysregulation in a subset of individual subjects. Study of larger cohorts and non-coding regulatory regions is warranted to define genetic risk factors for TC further. PMID- 25132216 TI - How can we improve models of care in inflammatory bowel disease? An international survey of IBD health professionals. AB - BACKGROUND AND AIMS: Few studies have specifically examined models of care in IBD. This survey was designed to help gather information from health professionals working in IBD services on current care models, and their views on how to best reshape existing models for IBD care worldwide. METHODS: An online mixed-methods survey was conducted with health professionals caring for IBD patients. Recruitment was conducted using the snowballing technique, where members of professional networks of the investigators were invited to participate. Results of the survey were summarised using descriptive statistics. RESULTS: Of the 135 included respondents, 76 (56%) were female, with a median age of 44 (range: 23-69) years, 50% were GI physicians, 34% nurses, 8% psychologists, 4% dieticians, 2% surgeons, 1% psychiatrists, and 1% physiotherapists. Overall, 73 (54%) respondents considered their IBD service to apply the integrated model of care, and only 5% reported that they worked exclusively using the biomedical care (no recognition of psychosocial factors). The majority of respondents reported including mental health assessment in their standard IBD care (65%), 51% believed that an ideal IBD service should be managed in specialist led clinics, and 64% wanted the service to be publicly funded. Respondents pictured an ideal IBD service as easy-access fully multi-disciplinary, with a significant role for IBD nurses and routine psychological and nutritional assessment and care. CONCLUSIONS: Health care professionals believe that an ideal IBD service should: be fully integrated, involve significant roles of nurses, psychologists and dieticians, run in specialist clinics, be easily accessible to patients and publicly funded. PMID- 25132217 TI - An automated protocol for performance benchmarking a widefield fluorescence microscope. AB - Widefield fluorescence microscopy is a highly used tool for visually assessing biological samples and for quantifying cell responses. Despite its widespread use in high content analysis and other imaging applications, few published methods exist for evaluating and benchmarking the analytical performance of a microscope. Easy-to-use benchmarking methods would facilitate the use of fluorescence imaging as a quantitative analytical tool in research applications, and would aid the determination of instrumental method validation for commercial product development applications. We describe and evaluate an automated method to characterize a fluorescence imaging system's performance by benchmarking the detection threshold, saturation, and linear dynamic range to a reference material. The benchmarking procedure is demonstrated using two different materials as the reference material, uranyl-ion-doped glass and Schott 475 GG filter glass. Both are suitable candidate reference materials that are homogeneously fluorescent and highly photostable, and the Schott 475 GG filter glass is currently commercially available. In addition to benchmarking the analytical performance, we also demonstrate that the reference materials provide for accurate day to day intensity calibration. Published 2014 Wiley Periodicals Inc. PMID- 25132218 TI - How mobile health can help tackle the diabetes epidemic and strengthen health systems: International Diabetes Federation (IDF) response to the public consultation on the European Commission's Green Paper on mobile health. PMID- 25132215 TI - Decreased effective connectivity from cortices to the right parahippocampal gyrus in Alzheimer's disease subjects. AB - The purpose of this study was to detect effective connectivity (EC) changes in the default mode network and hippocampus network in 20 patients with Alzheimer's disease (AD) and 20 cognitively normal (CN) subjects, using multivariate Granger causality. The authors used the maximum coefficients in the multivariate autoregression model to quantitatively measure the different EC strength levels between the CN and AD groups. It was demonstrated that the EC strength difference can classify AD from CN subjects. Further, the right parahippocampal gyrus (PHP_R) showed imbalanced bidirectional EC connections. The PHP_R received weaker input connections from the neocortices, but its output connections were significantly increased in AD. These findings may provide neural physiological mechanisms for interpreting AD subjects' memory deficits during the encoding processes. PMID- 25132219 TI - Determining the return on investment for evidence-based practice: an essential skill for all clinicians. PMID- 25132220 TI - Eye contact modulates cognitive processing differently in children with autism. AB - In humans, effortful cognitive processing frequently takes place during social interaction, with eye contact being an important component. This study shows that the effect of eye contact on memory for nonsocial information is different in children with typical development than in children with autism, a disorder of social communication. Direct gaze facilitated memory performance in children with typical development (n = 25, 6 years old), but no such facilitation was seen in the clinical group (n = 10, 6 years old). Eye tracking conducted during the cognitive test revealed strikingly similar patterns of eye movements, indicating that the results cannot be explained by differences in overt attention. Collectively, these findings have theoretical significance and practical implications for testing practices in children. PMID- 25132222 TI - Evaluation of therapeutic pulmonary surfactants by thin liquid film methods. AB - An example of the application of the Black Foam Film (BFF) Method and the Wetting Film Method, using the Microinterferomertric and the Pressure Balance Techniques, for characterization interfacial properties of the animal derived therapeutic pulmonary surfactant preparations (TSP), is presented. BFF thickness, probability of black film formation, and disjoining pressure for foam films from TSP aqueous solutions are measured as well as the wetting properties of TSP solutions on solid surfaces with different hydrophobicity have been studied. Interfacial characteristics such as minimal surfactant concentration to obtain black film (critical concentration) and concentration at which a black film is 100% obtained (threshold concentration) are determined. An evaluation of the four widely used TSP - Curosurf, Infasurf, Survanta, and Alveofact - by these methods has been carried out. Thus the methods of the thin liquid films are useful tools for studying the interfacial properties of TSP solutions, as well as for their improvement. PMID- 25132221 TI - Hyperfiltration is associated with the development of microalbuminuria in patients with sickle cell anemia. PMID- 25132223 TI - Structure of perfluorinated membranes investigated by method of standard contact porosimetry. AB - The results of investigation of various factors influencing water distribution in perfluorinated membrane structure by method of standard contact porosimetry are summarized. The Nafion membranes (Dupon de Nemoure, USA) and MF-4SK membranes ("Plastpolymer", Russia) were the objects of the research. The influence of production process and conditioning method on porosimetric curves of perfluorinated membrane is discussed. New results related to the porosity of perfluorinated membranes after reinforcing fabric introduction and processing by organic solvents are reported. The role of the modifying components of various nature in the shaping of transport channels in perfluorinated membrane is studied. The influence of polyaniline and hydrogen zirconium phosphate on water distribution in membrane structure is revealed. The correlation between the maximum porosity value of the membrane and its diffusion and electroosmotic permeability, as well as between the fraction of the gel pore volume and membrane selectivity is established. It allows the prediction of possible changes in the structural characteristics and also in the transport properties of the membranes under the influence of the modifying components of different types and various operating conditions. PMID- 25132224 TI - Efficacy of thiamethoxam and fipronil, applied alone and in combination, to control Limonius californicus and Hypnoidus bicolor (Coleoptera: Elateridae). AB - BACKGROUND: Wireworms, the larval stage of click beetles (family Elateridae), are significant soil pests of wheat and barley crops in the Pacific Northwest. At present, few pest management alternatives exist. For several decades, wireworms were effectively controlled by first-generation insecticides applied to the soil or as seed treatments. Currently used neonicotinoid insecticides protect crop seeds and germinating seedlings by temporary toxicity but limited mortality. As a result, field populations may increase, reaching levels too high for crop protection. In this study an investigation was made of the combination of two insecticides to achieve crop protection as well as insect mortality in wheat fields. RESULTS: Laboratory bioassays using wheat seed treated with fipronil at 1.0 and 5.0 g AI 100 kg(-1) seed resulted in 72-90% mortality of two wireworm species, Limonius californicus and Hypnoidus bicolor. At a rate of 39 g AI 100 kg(-1) seed, 8 times higher than the high rate of fipronil, thiamethoxam caused only 10-31% larval mortality in the bioassays, but did protect developing wheat stands from damage in field trials. Field plots planted with wheat seed treated with both fipronil (5.0 g AI 100 kg(-1) seed) and thiamethoxam (39.0 g AI 100 kg( 1) seed) had 83% fewer wireworms the following year compared with untreated check plots. No reduction in population was observed in plots treated with 39.0 g of thiamethoxam alone. CONCLUSIONS: Fipronil and thiamethoxam can be combined as a seed treatment to protect wheat crops from wireworm damage and reduce larval populations in the field. PMID- 25132226 TI - The role of complexation and competition in the biouptake of europium by a unicellular alga. AB - Short-term (60 min) europium (Eu) biouptake fluxes by the freshwater green alga Chlamydomonas reinhardtii were investigated in the presence and absence of ligands (e.g., malic acid and citric acid) and a second rare earth metal, samarium (Sm). Data were interpreted in the context of the biotic ligand model, which uses experimentally determined stability constants to take into account the competition and complexation of the metal of interest. In the absence of ligands or competitors, Eu biouptake was well described by a Michaelis-Menten equation with the maximal uptake flux (Jmax ) and Michaelis-Menten constant (Km ) of Jmax = 1.7 * 10(-14) mol cm(-2) s(-1) and Km = 10(-7.0) M (corresponding to an affinity constant of 10(7.0) M(-1) ). Biouptake of Eu (or Sm) decreased as the concentration of a competing rare earth element (i.e., Sm or Eu) increased, as predicted by the biotic ligand model. On the other hand, when hydrophilic complexes were formed with citric and malic acid, Eu biouptake was much greater than predicted on the basis of free ion concentrations alone. Overall, the results showed that for C. reinhardtii the rare earth elements were likely to share a common biouptake pathway; biouptake of one rare earth element was reduced when another was present, and rare earth element complexes were bioavailable. PMID- 25132225 TI - Nd: YAG laser posterior capsulotomy rates in myopic eyes after implantation of capsular tension ring. AB - BACKGROUND: The aim f this study was to evaluate the effect of capsular tension ring implantation during cataract surgery on the incidence of neodymium: YAG (Nd: YAG) laser posterior capsulotomy in myopic (axial length [AL] >=25.00 mm) eyes. MATERIAL/METHODS In this retrospective study, the records of the cases of 117 myopic patients who underwent cataract surgery between January 2004 and January 2011 were reviewed. A total of 153 eyes with an axial length of 25 mm or higher were included in the study with consideration of exclusion criteria mentioned below. Eyes were grouped by presence or lack of capsular tension ring (CTR+ and CTR-, respectively). RESULTS: The study included 153 eyes from 107 myopic patients. Hydrophilic acrylic IOL and capsular tension ring (CTR) were implanted in 78 eyes (CTR+ group), and 75 eyes received only the hydrophilic acrylic IOL (CTR- group). Six eyes (7.6%) in CTR+ and 16 eyes (21.3%) in CTR- required Nd: YAG laser capsulotomy within 7 years. The difference between the 2 groups was statistically significant (p=0.021). CONCLUSIONS: Because CTRs significantly decrease subsequent need for Nd: YAG laser posterior capsulotomy in myopic patients, are very inexpensive, and provide other benefits, our data suggest that the use of CTRs in myopic eyes undergoing cataract surgery with an hydrophilic acrylic IOL implantation is advantageous and should be standard practice. PMID- 25132227 TI - Birth preparedness and complication readiness among women of child bearing age group in Goba woreda, Oromia region, Ethiopia. AB - BACKGROUND: Birth preparedness and complication readiness is the process of planning for normal birth and anticipating the actions needed in case of an emergency. It is also a strategy to promote the timely use of skilled maternal care, especially during childbirth, based on the theory that preparing for childbirth reduces delays in obtaining this care. Therefore, the aim of this study was to assess birth preparedness and complication readiness among women of child bearing age group in Goba woreda, Oromia region, Ethiopia. METHODS: A community based cross sectional study was conducted in Goba woreda, Oromia region, Ethiopia. Multistage sampling was employed. Descriptive, binary and multiple logistic regression analyses were conducted. Statistically significant tests were declared at a level of significance of P value < 0.05. RESULTS: Only 29.9% of the respondents were prepared for birth and its complications. And, only 82 (14.6%) study participants were knowledgeable about birth preparedness and complication readiness.Variables having statistically significant association with birth preparedness and complication readiness of women were attending up to primary education (AOR = 3.24, 95% CI = 1.75, 6.02), attending up to secondary and higher level of education (AOR = 2.88, 95% CI = 1.34, 6.15), the presence of antenatal care follow up (AOR = 8.07, 95% CI = 2.41,27.00), knowledge about key danger signs during pregnancy (AOR = 1.74, 95% CI = 1.06,2.88), and knowledge about key danger signs during the postpartum period (AOR = 2.08, 95% CI = 1.20,3.60). CONCLUSIONS: Only a small number of respondents were prepared for birth and its complications. Furthermore, the vast majority of women were not knowledgeable about birth preparedness and complication readiness. Residence, educational status, ANC follow up, knowledge of key danger signs during pregnancy and the postpartum period were independent predictors of birth preparedness and complication readiness. PMID- 25132228 TI - Plasticity of vulnerability to leaf hydraulic dysfunction during acclimation to drought in grapevines: an osmotic-mediated process. AB - Previous studies have reported correlation of leaf hydraulic vulnerability with pressure-volume parameters related to cell turgor. This link has been explained on the basis of the effects of turgor on connectivity among cells and tissue structural integrity, which affect leaf water transport. In this study, we tested the hypothesis that osmotic adjustment to water stress would shift the leaf vulnerability curve toward more negative water potential (Psi leaf ) by increasing turgor at low Psi leaf . We measured leaf hydraulic conductance (K leaf ), K leaf vulnerability [50 and 80% loss of K leaf (P50 and P80 ); |Psi leaf | at 50 and 80% loss of K leaf , respectively), bulk leaf water relations, leaf gas exchange and sap flow in two Vitis vinifera cultivars (Tempranillo and Grenache), under two water treatments. We found that P50 , P80 and maximum K leaf decreased seasonally by more than 20% in both cultivars and watering treatments. However, K leaf at 2 MPa increased threefold, while osmotic potential at full turgor and turgor loss point decreased. Our results indicate that leaf resistance to hydraulic dysfunction is seasonally plastic, and this plasticity may be mediated by osmotic adjustment. PMID- 25132229 TI - Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann-Pick disease type C1 mice. AB - Progressive olfactory impairment is one of the earliest markers of neurodegeneration. However, the underlying mechanism for this dysfunction remains unclear. The present study investigated the possible role of microgliosis in olfactory deficits using a mouse model of Niemann-Pick disease type C1 (NPC1), which is an incurable neurodegenerative disorder with disrupted lipid trafficking. At 7weeks of age, NPC1 mutants showed a distinct olfactory impairment in an olfactory test compared with age-matched wild-type controls (WT). The marked loss of olfactory sensory neurons within the NPC1 affected olfactory bulb (NPC1-OB) suggests that NPC1 dysfunction impairs olfactory structure. Furthermore, the pool of neuroblasts in the OB was diminished in NPC1 mice despite the intact proliferative capacity of neural stem/progenitor cells in the subventricular zone. Instead, pro-inflammatory proliferating microglia accumulated extensively in the NPC1-OB as the disease progressed. To evaluate the impact of abnormal microglial activation on olfaction in NPC1 mice, a microglial inhibition study was performed using the anti-inflammatory agent Cyclosporin A (CsA). Importantly, long-term CsA treatment in NPC1 mice reduced reactive microgliosis, restored the survival of newly generated neurons in the OB and improved overall performance on the olfactory test. Therefore, our study highlights the possible role of microglia in the regulation of neuronal turnover in the OB and provides insight into the possible therapeutic applications of microglial inhibition in the attenuation or reversal of olfactory impairment. PMID- 25132230 TI - Central type primitive neuroectodermal tumor/neuroblastoma of the uterus: a case report. AB - We encountered a 63-year-old woman who had a uterine tumor with peritoneal dissemination and para-aortic lymph node metastasis. Microscopic specimens of the tumor showed a small blue round-cell tumor. Immunohistochemistry showed cells to be negative for cytokeratin AE1/3, desmin, myogenin, CD10, CD34, and CD99, focal positive for vimentin, and positive for muscle-specific actin (HHF-35), neurofilament, synaptophysin and CD56. Fluorescence in situ hybridization revealed no split signal showing Ewing sarcoma breakpoint region 1 gene translocation. Deletion of 1p36 was identified in 30% of the tumor cells. These findings are thought to be equivalent to central type primitive neuroectodermal tumors/neuroblastoma. Cytoreductive debulking surgery followed by chemotherapy, including cyclophosphamide, vincristine and adriamycin, resulted in complete remission. She has no evidence of disease at 24 months after surgery. PMID- 25132231 TI - Microbial weeds in hypersaline habitats: the enigma of the weed-like Haloferax mediterranei. AB - Heterotrophic prokaryotic communities that inhabit saltern crystallizer ponds are typically dominated by two species, the archaeon Haloquadratum walsbyi and the bacterium Salinibacter ruber, regardless of location. These organisms behave as 'microbial weeds' as defined by Cray et al. (Microb Biotechnol 6: 453-492, 2013) that possess the biological traits required to dominate the microbiology of these open habitats. Here, we discuss the enigma of the less abundant Haloferax mediterranei, an archaeon that grows faster than any other, comparable extreme halophile. It has a wide window for salt tolerance, can grow on simple as well as on complex substrates and degrade polymeric substances, has different modes of anaerobic growth, can accumulate storage polymers, produces gas vesicles, and excretes halocins capable of killing other Archaea. Therefore, Hfx. mediterranei is apparently more qualified as a 'microbial weed' than Haloquadratum and Salinibacter. However, the former differs because it produces carotenoid pigments only in the lower salinity range and lacks energy-generating retinal-based, light driven ion pumps such as bacteriorhodopsin and halorhodopsin. We discuss these observations in relation to microbial weed biology in, and the open-habitat ecology of, hypersaline systems. PMID- 25132232 TI - Physiatry practice now and in 2032: how to thrive in the post-health care reform world. AB - Health care reform is upon us, including changes in models of care delivery and physician and institution compensation. The resulting tsunami of uncertainty offers physiatrists the opportunity to relocate to higher ground and help the specialty thrive as well as to identify the possible quagmires into which practices could sink. For this reason, it is prudent for physiatrists to more carefully consider how their professional lives may be altered in the aftermath of reform. We believe that understanding and preparation will facilitate opportunities and mitigate challenges. In this essay, we will discuss various alternative scenarios that represent population health and health care delivery in the year 2032, the real-world opportunities and challenges for the physiatrist in the present and in the next 2 decades, along with ideas as to how physiatry can thrive in the post-health care reform world. PMID- 25132233 TI - Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio index and fibrosis-4 index for detecting liver fibrosis in adult patients with chronic hepatitis B virus infection: a systemic review and meta-analysis. AB - The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (Fibrosis 4 index; FIB-4) are the two most widely studied noninvasive tools for assessing liver fibrosis. Our aims were to systematically review the performance of APRI and FIB-4 in hepatitis B virus (HBV) infection in adult patients and compare their advantages and disadvantages. We examined the diagnostic accuracy of APRI and FIB-4 for significant fibrosis, advanced fibrosis, and cirrhosis based on their sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUROC). Heterogeneity was explored using metaregression. Our systemic review and meta-analysis included 16 articles of APRI only, 21 articles of APRI and FIB-4 and two articles of FIB-4 for detecting different levels of liver fibrosis. With an APRI threshold of 0.5, 1.0, and 1.5, the sensitivity and specificity values were 70.0% and 60.0%, 50.0% and 83.0%, and 36.9% and 92.5% for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. With an FIB-4 threshold of 1.45 and 3.25, the sensitivity and specificity values were 65.4% and 73.6% and 16.2% and 95.2% for significant fibrosis. The summary AUROC values using APRI and FIB-4 for the diagnosis of significant fibrosis, advanced fibrosis, and cirrhosis were 0.7407 (95% confidence interval [CI]: 0.7033-0.7781) and 0.7844 (95% CI: 0.7450-0.8238; (Z = 1.59, P = 0.06), 0.7347 (95% CI: 0.6790-0.7904) and 0.8165 (95% CI: 0.7707 0.8623; Z = 2.01, P = 0.02), and 0.7268 (95% CI: 0.6578-0.7958) and 0.8448 (95% CI: 0.7742-0.9154; (Z = 2.34, P = 0.01), respectively. CONCLUSIONS: Our meta analysis suggests that APRI and FIB-4 can identify hepatitis B-related fibrosis with a moderate sensitivity and accuracy. PMID- 25132234 TI - Same but different: tuberculosis treatment and care among migrants from different countries of origin in Israel. AB - INTRODUCTION: Israel hosts documented labor migrants (DLM), and recently also undocumented migrants (UDM), mostly from Horn of Africa. This study aims to compare treatment outcomes and other clinical aspects between a sample of 154 DLM and 113 UDM who were treated in two tuberculosis clinics between 2005 and 2010. RESULTS AND DISCUSSION: Compared to DLM, UDM were younger males, stayed in Israel for shorter periods, had lower coverage of medical insurance, were less likely to be employed, and had greater difficulties in communication with the medical staff. UDM were more likely to demonstrate tuberculosis-related symptoms than DLM, were more commonly diagnosed with pulmonary TB, and had shorter patient and system delays and their treatment success rate was better than DLM, who were more likely to be transferred out. CONCLUSION: UDM achieved better treatment outcomes, as they were screened upon entry and treatment was initiated in detention, while DLM were diagnosed in the community and may have felt more secure to abandon treatment. PMID- 25132235 TI - Does preconception care work? AB - BACKGROUND: To date, there is a lack of evidence to suggest that a systematic and coordinated approach to prepregnancy care might make a difference. AIMS: To evaluate whether women who receive preconception care through a structured approach will be more likely to be healthy around the time of conception compared with women who plan their pregnancy but have not been exposed to preconception care. METHODS: A case control study was undertaken of women who attended the preconception care service and subsequently conceived, received maternity care and gave birth at Mater Health Services Brisbane between January 2010 and January 2013. Pregnancy information and birth outcomes for each woman who attended the service were matched with those of three women who reported that they had planned their pregnancy but did not attend the service. Records were matched for prepregnancy BMI, age, parity, prepregnancy smoking status and number of health conditions. RESULTS: Pregnant women who attended preconception care were more likely to have received adequate peri-conceptual folate, to report being vaccinated against influenza and hepatitis B, to have consulted with a specialist with the specific aim of optimising a pre-existing health condition and to report less weight gain up until booking. Preterm birth and hypertensive disorders of pregnancy were less common amongst women who had attended preconception care, and there were trends towards a decreased incidence of gestational diabetes, LGA and fetal anomalies. CONCLUSION: These preliminary data provide some optimism that a comprehensive preconception care service may positively influence maternal and neonatal outcomes. PMID- 25132236 TI - Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome. AB - Cowden syndrome (CS) is an autosomal dominant hereditary cancer syndrome causing increased risk for breast, thyroid, renal, uterine, and other cancers as well as benign neoplasias and neurodevelopmental concerns. Timely diagnosis of affected patients is key, as early recognition allows for high-risk screening and other preventative measures prior to a patient enduring multiple cancer diagnoses. This review will highlight the cardinal features of CS and management recommendations for affected patients. PMID- 25132237 TI - Genome-wide analysis reveals artificial selection on coat colour and reproductive traits in Chinese domestic pigs. AB - Pigs from Asia and Europe were independently domesticated from c. 9000 years ago. During this period, strong artificial selection has led to dramatic phenotypic changes in domestic pigs. However, the genetic basis underlying these morphological and behavioural adaptations is relatively unknown, particularly for indigenous Chinese pigs. Here, we performed a genome-wide analysis to screen 196 regions with selective sweep signals in Tongcheng pigs, which are a typical indigenous Chinese breed. Genes located in these regions have been found to be involved in lipid metabolism, melanocyte differentiation, neural development and other biological processes, which coincide with the evolutionary phenotypic changes in this breed. A synonymous substitution, c.669T>C, in ESR1, which colocalizes with a major quantitative trait locus for litter size, shows extreme differences in allele frequency between Tongcheng pigs and wild boars. Notably, the variant C allele in this locus exhibits high allele frequency in most Chinese populations, suggesting a consequence of positive selection. Five genes (PRM1, PRM2, TNP2, GPR149 and JMJD1C) related to reproductive traits were found to have high haplotype similarity in Chinese breeds. Two selected genes, MITF and EDNRB, are implied to shape the two-end black colour trait in Tongcheng pig. Subsequent SNP microarray studies of five Chinese white-spotted breeds displayed a concordant signature at both loci, suggesting that these two genes are responsible for colour variations in Chinese breeds. Utilizing massively parallel sequencing, we characterized the candidate sites that adapt to artificial and environmental selections during the Chinese pig domestication. This study provides fundamental proof for further research on the evolutionary adaptation of Chinese pigs. PMID- 25132238 TI - The cistrome and gene signature of androgen receptor splice variants in castration resistant prostate cancer cells. AB - PURPOSE: Spliced variant forms of androgen receptor were recently identified in castration resistant prostate cancer cell lines and clinical samples. We identified the cistrome and gene signature of androgen receptor splice variants in castration resistant prostate cancer cell lines and determined the clinical significance of androgen receptor splice variant regulated genes. MATERIALS AND METHODS: The castration resistant prostate cancer cell line 22Rv1, which expresses full-length androgen receptor and androgen receptor splice variants endogenously, was used as the research model. We established 22Rv1-ARFL(-)/ARV(+) and 22Rv1-ARFL(-)/ARV(-) through RNA interference. Chromatin immunoprecipitation coupled with next generation sequencing and microarray techniques were used to identify the cistrome and gene expression profiles of androgen receptor splice variants in the absence of androgen. RESULTS: Androgen receptor splice variant binding sites were identified in 22Rv1-ARFL(-)/ARV(+). A gene set was regulated uniquely by androgen receptor splice variants but not by full-length androgen receptor in the absence of androgen. Integrated analysis revealed that some genes were directly modulated by androgen receptor splice variants. Unsupervised clustering analysis showed that the androgen receptor splice variant gene signature differentiated benign from malignant prostate tissue as well as localized prostate cancer from metastatic castration resistant prostate cancer specimens. Some genes that were modulated uniquely by androgen receptor splice variants also correlated with histological grade and biochemical failure. CONCLUSIONS: Androgen receptor splice variants can bind to DNA independent of full-length androgen receptor in the absence of androgen and modulate a unique set of genes that is not regulated by full-length androgen receptor. The androgen receptor splice variant gene signature correlates with disease progression. It distinguishes primary cancer from castration resistant prostate cancer specimens and benign from malignant prostate specimens. PMID- 25132240 TI - Single fraction radiosurgery for the treatment of renal tumors. AB - PURPOSE: High dose local stereotactic radiosurgery was performed in select patients to improve local tumor control and overall survival. We report on patients with renal tumors treated with single fraction robotic stereotactic radiosurgery. MATERIALS AND METHODS: A total of 40 patients with a median age of 64 years who had an indication for nephrectomy and subsequent hemodialysis were entered in a prospective case-control study of single fraction stereotactic radiosurgery. Of the patients 11 had transitional cell cancer and 29 had renal cell cancer. Tumor response, renal function, survival and adverse events were estimated every 3 months. Followup was at least 6 months. RESULTS: A total of 45 renal tumors were treated. Median followup was 28.1 months (range 6.0 to 78.3). The local tumor control rate 9 months after stereotactic radiosurgery was 98% (95% CI 89-99). There was a measurable size reduction in 38 lesions, including complete remission in 19. Renal function remained stable. Using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation median creatinine clearance was 76.8 (range 25.3 to 126.3) and 70.3 ml/minute/1.73 m(2) (range 18.6 to 127.3) at baseline and followup, respectively (p = 0.89). Grade I erythrodermia developed in 1 patient, 3 reported grade I fatigue and 2 reported grade I nausea. Nephrectomy was avoided in all cases. CONCLUSIONS: Single fraction stereotactic radiosurgery as an outpatient procedure is a treatment modality with short-term safety and efficacy. It avoids treatment related loss of renal function and hemodialysis in select patients with transitional or renal cell cancer. At short followup oncologic results were similar to those of other ablative techniques for renal tumors. To date functional results have been excellent. Further studies are needed to determine the long-term results and limits of stereotactic radiosurgery in this setting. PMID- 25132239 TI - Increased brain gray matter in the primary somatosensory cortex is associated with increased pain and mood disturbance in patients with interstitial cystitis/painful bladder syndrome. AB - PURPOSE: Interstitial cystitis is a highly prevalent pain condition estimated to affect 3% to 6% of women in the United States. Emerging data suggest there are central neurobiological components to the etiology of this disease. We report the first brain structural imaging findings from the MAPP network with data on more than 300 participants. MATERIALS AND METHODS: We used voxel based morphometry to determine whether human patients with chronic interstitial cystitis display changes in brain morphology compared to healthy controls. A total of 33 female patients with interstitial cystitis without comorbidities and 33 age and gender matched controls taken from the larger sample underwent structural magnetic resonance imaging at 5 MAPP sites across the United States. RESULTS: Compared to controls, females with interstitial cystitis displayed significant increased gray matter volume in several regions of the brain including the right primary somatosensory cortex, the superior parietal lobule bilaterally and the right supplementary motor area. Gray matter volume in the right primary somatosensory cortex was associated with greater pain, mood (anxiety) and urological symptoms. We explored these correlations in a linear regression model, and found independent effects of these 3 measures on primary somatosensory cortex gray matter volume, namely clinical pain (McGill pain sensory total), a measure of urgency and anxiety (HADS). CONCLUSIONS: These data support the notion that changes in somatosensory gray matter may have an important role in pain sensitivity as well as affective and sensory aspects of interstitial cystitis. Further studies are needed to confirm the generalizability of these findings to other pain conditions. PMID- 25132242 TI - Evaluation of outcome and prognostic factors in extraosseous Ewing sarcoma. AB - BACKGROUND: Data on extraosseous Ewing sarcoma (EES) with uniform chemotherapy protocol are minimal. We aimed to examine this aspect in our patients, identify prognostic factors and compare the same with osseous Ewing sarcoma. PROCEDURES: A single institutional data review of patients with EES treated between June 2003 and November 2011 with uniform chemotherapy and evaluated on intent-to-treat analysis was done. RESULTS: Of 374 patients with Ewing sarcoma, 60 (16%) were EES with median age 16 years; 20 (33%) had metastases. After median follow-up of 25 months (range: 1.7-104.4), 5-year event free survival (EFS), OS, and local control-rate were 47.1 +/- 7.9%, 61.6 +/- 7.8%, and 77.9 +/- 8.6%, respectively for entire EES cohort. In multivariate analysis, hemoglobin <= 10 g/dl (P = 0.03), and white blood cell count (WBC) >11 * 10(9) /L (P = 0.009) predicted inferior EFS for the entire EES cohort. Low hemoglobin (P = 0.05) and high LDH (P = 0.01) predicted inferior OS for the entire EES cohort on multivariate analysis. As compared to the cohort of skeletal primary (n = 314), higher proportion of patients underwent surgery in the cohort of EES (P = .003); EFS (P = 0.004) and OS (P = 0.08) were superior for patients with EES than patients with skeletal Ewing sarcoma. CONCLUSION: These data of EES suggests that low hemoglobin and high WBC count adversely affect EFS. Overall outcome was significantly better for EES than skeletal primary tumors. PMID- 25132241 TI - A role for PERK in the mechanism underlying fluoride-induced bone turnover. AB - While it has been well-documented that excessive fluoride exposure caused the skeletal disease and osteoblasts played a critical role in the advanced skeletal fluorosis, the underlying mechanism that mediated these effects remain poorly understood. The present study was undertaken to examine the effect of fluoride on bone of rats and MC3T3-E1 cells in vitro. Herein we found pathological features of high bone turnover in fluoride-treated rats, which was supported by an increase of osteogenic and osteoclastogenic genes expression in different stages of fluoride exposure. The skeletal toxicity of fluoride was accompanied by activation of endoplasmic reticulum (ER) stress and subsequent unfolded protein response (UPR). A novel finding of this study was that expression of PKR-like endoplasmic reticulum kinase (PERK) was the same trend with receptor activator for nuclear factor-kappa B ligand (RANKL), and NF-E2 p45-related factor 2 (Nrf2) was the same trend with Runt-related transcription factor 2 (Runx2) in bones of rats exposed to varied fluoride condition. Based on these data, we hypothesized that up-regulation of PERK probably played a role in mediating bone turnover induced by fluoride. Action of fluoride on MC3T3-E1 cells differentiation was demonstrated through analysis of alkaline phosphatase (ALP) activity and mineralized nodules formation. Meantime, an increase of binding immunoglobulin protein (BiP) expression indicated the active ER stress in cells exposed to various dose of fluoride. Blocking PERK expression using siRNA showed the obvious decrease of osteogenic and osteoclastogenic factors expression in MC3T3-E1 cells exposed to certain dose of fluoride that could positively stimulate osteoblastic viability. In conclusion these findings underscore the importance of PERK in modulating fluoride induced bone formation and bone resorption. Understanding the link between PERK and bone turnover could probe into the mechanism underlying different bone lesion of skeletal fluorosis. PMID- 25132244 TI - Keeping up with the Cadillacs: What Health Insurance Disparities, Moral Hazard, and the Cadillac Tax Mean to The Patient Protection and Affordable Care Act. AB - A major goal of The Patient Protection and Affordable Care Act is to broaden health care access through the extension of insurance coverage. However, little attention has been given to growing disparities in access to health care among the insured, as trends to reduce benefits and increase cost sharing (deductibles, co-pays) reduce affordability and access. Through a political economic perspective that critiques moral hazard, this article draws from ethnographic research with the United Steelworkers (USW) at a steel mill and the Retail, Wholesale and Department Store Union (RWDSU) at a food-processing plant in urban Central Appalachia. In so doing, this article describes difficulties of health care affordability on the eve of reform for differentially insured working families with employer-sponsored health insurance. Additionally, this article argues that the proposed Cadillac tax on high-cost health plans will increase problems with appropriate health care access and medical financial burden for many families. PMID- 25132243 TI - Natural calamities and 'the Big Migration': challenges to the Mongolian health system in 'the Age of the Market'. AB - Beginning with the demise of the socialist state system in 1990, Mongolia embarked on a process of neoliberal economic reform, initiating what is known among the Mongols as 'the Age of the Market'. The socialist health system has been replaced by a series of reforms initiated and substantiated by foreign donor organisations. This paper critically examines Mongolia's health system and discusses the extent to which this 'system', despite its provision of universal, accessible and essential primary health care services, is unable to accommodate the health needs of poor urban in-migrants and nomadic herders in remote provinces. With a particular focus on recurrent natural winter disasters (dzud) and an escalating rural to urban migration, the paper argues that the issues of access to health services and health system strengthening must be understood in relation to factors external to the health system. Ethnographic research highlights that despite a growing economy, considerable external aid and an established primary health care model, weak rural politics, environmental challenges and economic constraints create escalating health vulnerability among the poorest in Mongolia. PMID- 25132245 TI - What is the optimal treatment for presbyphonia? PMID- 25132246 TI - Reply: can implanted venous access ports remain patent without maintenance flush lock? PMID- 25132247 TI - Does dexmedetomidine have a cardiac protective effect during non-cardiac surgery? A randomised controlled trial. AB - This study was designed to determine the effects of dexmedetomidine on perioperative myocardial injury by observing peripheral circulatory changes in response to tracheal intubation and extubation, myocardial enzyme levels, myocardial ischaemia improvements, cardiovascular adverse events and cytokines in patients with coronary heart disease (CHD) undergoing non-cardiac surgery. This study was a prospective, randomized, double-blind trial. Eighty patients having CHD were scheduled for elective hip-replacement surgery and randomly allocated to receive a loading dose of 1 MUg/kg dexmedetomidine followed by a 0.2 MUg/kg per h infusion (Dex group; n = 40) or normal saline (control group; n = 40). Systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, rate-pressure product and changes in ST-T segment on the electrocardiogram were recorded every 5 min during surgery. Serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), glycogen phosphorylase BB (GP-BB), interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha protein levels were determined preoperatively, at the end of surgery and 12 and 24 h after surgery. The improvement rate of myocardial ischaemia was higher in the Dex than control group (87.5% vs 32.5%, respectively; P < 0.05). In addition, the Dex group had lower serum CK-MB, IL-6, cTnI and GP-BB concentrations than the control group (P < 0.05). There was no significance difference in TNF-alpha between the two groups (P > 0.05). Dexmedetomidine can reduce myocardial injury and cytokine levels in patients with CHD undergoing non-cardiac surgery. PMID- 25132249 TI - Considerations in understanding the ocular surface microbiome. PMID- 25132250 TI - Choroidal changes associated with bruch membrane pathology in pseudoxanthoma elasticum. PMID- 25132248 TI - Association of interleukin-8 and neutrophils with nasal symptom severity during acute respiratory infection. AB - Using a large data set (n = 811), the relationship between acute respiratory infection illness severity and inflammatory biomarkers was investigated to determine whether certain symptoms are correlated more closely than others with the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils. Participants with community acquired acute respiratory infection underwent nasal lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain reaction (PCR) methods for the detection and identification of respiratory viruses. Information about symptoms was obtained throughout the duration of the illness episode using the well-validated Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Global symptom severity was calculated by the area under the curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56% were positively identified for one or more of nine different respiratory viruses. During acute respiratory infection illness, both IL-8 and neutrophils positively correlate with AUC (r(s) = 0.082, P = 0.022; r(s) = 0.080, P = 0.030). IL-8 and neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = < 0.00001; r = 0.18, P = < 0.003), plugged nose (r = 0.045, P = 0.003; r = 0.14, P = 0.058), and sneezing (r = -0.02, P = < 0.0001; r = -0.0055, P = 0.31). Neutrophils correlate with some quality of life measures such as sleeping well (r = 0.15, P = 0.026). Thus, the study demonstrates that IL-8 and neutrophils are correlated with severity of nasal symptoms during acute respiratory infection. Further research is necessary to determine if the concentration of these or other biomarkers can predict the overall duration and severity of acute respiratory infection illness. PMID- 25132251 TI - Importance of birth weight as a risk factor for severe retinopathy of prematurity when gestational age is 30 or more weeks. PMID- 25132252 TI - Reply: To PMID 24727260. PMID- 25132253 TI - Clinical manifestations of patients with intraocular inflammation and positive QuantiFERON-TB gold in-tube test in a country nonendemic for tuberculosis. PMID- 25132254 TI - Reply: To PMID 24582994. PMID- 25132255 TI - Pancreatic surgical biopsy in 24 dogs and 19 cats: postoperative complications and clinical relevance of histological findings. AB - OBJECTIVE: To assess the immediate postoperative complications associated with pancreatic biopsy in dogs and cats and review the clinical relevance of biopsy findings. METHODS: Retrospective review of clinical records from two referral institutions for cases undergoing pancreatic biopsy between 2000 and 2013. RESULTS: Twenty-four dogs and 19 cats that had surgical pancreatic biopsy had sufficient detail in their clinical records and fulfilled the inclusion criteria. Postoperative complications were seen in 10 cases of which 5 were suggestive of post-surgical pancreatitis. Two patients were euthanased within 10 days of surgery because of the underlying disease; neither suffered postoperative complications. Pancreatic pathology was found in 19 cases, 7 cases showed no change other than benign pancreatic nodular hyperplasia, and no abnormalities were seen in 18 cases. CLINICAL SIGNIFICANCE: Complications may be encountered following surgical pancreatic biopsy, although the risk should be minimal with good surgical technique. Pancreatic biopsy may provide a useful contribution to case management but it is not clear whether a negative pancreatic biopsy should be used to rule out pancreatic disease. Dogs were more likely to have no significant pathology found on pancreatic biopsy than cats, where chronic pancreatitis was the most common finding. PMID- 25132256 TI - Effect of Astragalus polysaccharides on expression of TNF-alpha, IL-1beta and NFATc4 in a rat model of experimental colitis. AB - AIM: Astragalus membranaceus is a Chinese medicinal herb and has been shown to improve hapten-induced experimental colitis. One of its major components is polysaccharides. We investigated the effect of Astragalus polysaccharides (APS) on expression of TNF-alpha, IL-1beta and NFATc4 in a rat model of experimental colitis. METHODS: The experimental colitis model was induced by TNBS. Forty five rats were divided into five groups (n=9): Normal control group, receiving ethanol vehicle with no TNBS during induction and IP saline injection during treatment; TNBS colitis model group (TNBS+IP saline), receiving only IP saline vehicle treatment; APS low dose group (TNBS+L-APS), receiving APS 100mg/kg; APS high dose group (TNBS+H-APS), receiving APS 200mg/kg; and positive control group (TNBS+Dexm), receiving dexamethasone 0.3mg/kg. The clinical features, macroscopic and microscopic scores were assessed. The expressions of TNF-alpha, IL-1beta and NFATc4 were measured by real-time PCR and ELISA assays. RESULTS: Compared to normal control rats, TNBS+IP saline had significant weight loss, increased macroscopic and microscopic scores, higher disease activity index (DAI) up regulation of TNF-alpha, IL-1beta and NFATc4 mRNA expression and up-regulation of TNF-alpha and IL-1beta protein expression. Compared to TNBS+IP saline, treatment with APS or dexamethasone significantly reduced DAI, partially but significantly prevented TNBS colitis-induced weight loss and improved both macroscopic and microscopic scores; high dose APS or dexamethasone significantly down-regulated TNF-alpha and IL-1beta expressions (both mRNA and protein) and up-regulated NFATc4 mRNA and protein expression. The effect of high dose APS and dexamethasone is comparable. CONCLUSIONS: APS significantly improved experimental TNBS-induced colitis in rats through regulation of TNF-alpha, IL-1beta and NFATc4 expression. PMID- 25132257 TI - Biomechanical comparison of a locking compression plate combined with an intramedullary pin or a polyetheretherketone rod in a cadaveric canine tibia gap model. AB - OBJECTIVE: To compare the biomechanical properties of a 10-hole 3.5 mm locking compression plate (LCP) with 2 proximal and 2 distal bicortical locked screws reinforced with either a Steinmann pin of 30-40% the medullary diameter or a poly ether-ether-ketone (PEEK) rod of ~75% the medullary diameter in a cadaveric tibia gap model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Cadaveric canine tibias (n = 8 pair). METHODS: Each construct had a 10-hole 3.5 mm LCP with 2 screws per fracture fragment using a comminuted tibia gap model. The Steinmann pin constructs had a 2.4 mm intramedullary pin whereas the PEEK-rod constructs had a 6 mm intramedullary PEEK rod placed. Biomechanical testing included non destructive bi-planar 4 point bending, torsion testing, and destructive axial compression. Testing produced the responses of failure load (N) in axial compression, stiffness (N/mm or N/ degrees ) in axial compression, torsion, lateral-medial, and caudal-cranial 4 point bending. Screw position within the PEEK-rods was determined after explantation. RESULTS: The PEEK-rod constructs were significantly stiffer in axial compression (P < .005), lateral-medial 4 point bending (P < .001), and in torsional loading (P < .031) than the Steinman pin constructs. There was no significant difference between the constructs for stiffness in caudal-cranial 4 point bending (P = .32). The PEEK-rod constructs failed at a significantly higher load than the Steinmann pin constructs (P < .001). All constructs failed by yielding through plastic deformation. Each screw penetrated the PEEK rod in all constructs but the position of the screw varied. CONCLUSION: PEEK-rod constructs failed at significantly higher loads and were significantly stiffer in 4 point lateral-medial bending, axial compression, and torsion when compared with Steinmann pin constructs. PMID- 25132258 TI - Retinoic acid receptor-alpha up-regulates proopiomelanocortin gene expression in AtT20 corticotroph cells. AB - Cushing's disease is a disorder caused by excessive ACTH secretion from a corticotroph tumor of the pituitary gland. Although its standard therapy is a transsphenoidal surgery, innovation of novel medical treatments for the disease is urgently necessary. Retinoic acid (RA) has been reported to suppress adrenocorticotropic hormone (ACTH) secretion in Cushing's disease. However, the role of RA receptor (RAR) in proopiomelanocortin (Pomc) gene expression remains uncertain. We here examined the involvement of RARalpha in Pomc regulation using AtT20 corticotroph cells. Surprisingly, a synthetic RARalpha agonist Am80 increased Pomc mRNA expression, CRH-induced ACTH secretion, and Pomc promoter activity. Small interfering RNA-mediated RARalpha-knockdown suppressed both basal and Am80-induced Pomc promoter activity. RARalpha-overexpression dose-dependently increased Pomc promoter activity. Pomc promoter mutation analysis revealed that both Tpit and NeuroD1 binding elements were responsible for the Am80-mediated effect. Am80 increased Tpit expression while RAR antagonist LE540 suppressed the increase. Tpit-overexpression increased Pomc promoter activity. Mammalian two hybrid assay revealed that Am80 induced NeuroD1-RARalpha interaction. NeuroD1 overexpression enhanced the Am80-induced Pomc promoter activity, which was suppressed by NeuroD1 truncated mutant-overexpression. RARalpha thus positively regulates ACTH secretion/Pomc gene expression through interaction with NeuroD1 and Tpit expression increase. The present observation will be useful for the future development of the RA/retinoid-derived therapeutics of the disease. PMID- 25132259 TI - [Nursing and the humanization of the end- of-life care within healthcare systems]. AB - The reflection upon the humanisation of the end-of-life process within healthcare systems and the implication of healthcare professionals is the main objective of this article. The evolution of the model of care and nurses leadership role at the end-of-life process is evaluated. This analysis starts from the first European references regarding advance wills, made in 1997 at the Oviedo Convention, until the introduction of the idea of advance directives incorporated into Spanish law in 2002. It sets the concept of advance planning in health related decisions, which establishes a process of voluntary dialogue where every person can clarify values, preferences and wishes regarding the final moments of life, with the support of the healthcare professionals. PMID- 25132260 TI - CCN5/WISP-2 promotes growth arrest of triple-negative breast cancer cells through accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation. AB - The matricellular protein CCN5/WISP-2 represents a promising target in triple negative breast cancer (TNBC) because treatment or induced activation of CCN5 in TNBC cells promotes cell growth arrest at the G0/G1 phase, reduces cell proliferation and delays tumor growth in the xenograft model. Our studies found that the p27(Kip1) tumor suppressor protein is upregulated and relocalized to the nucleus from cytoplasm by CCN5 in these cells and that these two events (upregulation and relocalization of p27(Kip1)) are critical for CCN5-induced growth inhibition of TNBC cells. In the absence of CCN5, p27(Kip1) resides mostly in the cytoplasm, which is associated with the aggressive nature of cancer cells. Mechanistically, CCN5 inhibits Skp2 expression, which seems to stabilize the p27(Kip1) protein in these cells. On the other hand, CCN5 also recruits FOXO3a to mediate the transcriptional regulation of p27(Kip1). The recruitment of FOXO3a is achieved by the induction of its expression and activity through shifting from cytoplasm to the nucleus. Our data indicate that CCN5 blocks PI3K/AKT signaling to dephosphorylate at S318, S253 and Thr32 in FOXO3a for nuclear relocalization and activation of FOXO3a. Moreover, inhibition of alpha6beta1 receptors diminishes CCN5 action on p27(Kip1) in TNBC cells. Collectively, these data suggest that CCN5 effectively inhibits TNBC growth through the accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation, and thus, activation of CCN5 may have the therapeutic potential to kill TNBC. PMID- 25132261 TI - Neuropeptide Y receptor Y5 as an inducible pro-survival factor in neuroblastoma: implications for tumor chemoresistance. AB - Neuroblastoma (NB) is a pediatric tumor of neural crest origin with heterogeneous phenotypes. Although low-stage tumors carry a favorable prognosis, >50% of high risk NB relapses after treatment with a fatal outcome. Thus developing therapies targeting refractory NB remains an unsolved clinical problem. Brain-derived neurotrophic factor (BDNF) and its TrkB receptor are known to protect NB cells from chemotherapy-induced cell death, while neuropeptide Y (NPY), acting via its Y2 receptor (Y2R), is an autocrine proliferative and angiogenic factor crucial for maintaining NB tumor growth. Here we show that in NB cells, BDNF stimulates the synthesis of NPY and induces expression of another one of its receptors, Y5R. In human NB tissues, the expression of NPY and Y5R positively correlated with the expression of BDNF and TrkB. Functionally, BDNF triggered Y5R internalization in NB cells, whereas Y5R antagonist inhibited BDNF-induced p44/42 mitogen-activated protein kinase activation and its pro-survival activity. These observations suggested TrkB-Y5R transactivation that resulted in cross-talk between their signaling pathways. Additionally, NPY and Y5R were upregulated in a BDNF independent manner in NB cells under pro-apoptotic conditions, such as serum deprivation and chemotherapy, as well as in cell lines and tissues derived from posttreatment NB tumors. Blocking Y5R in chemoresistant NB cells rich in this receptor sensitized them to chemotherapy-induced apoptosis and inhibited their growth in vivo by augmenting cell death. In summary, the NPY/Y5R axis is an inducible survival pathway activated in NB by BDNF or cellular stress. Upon such activation, Y5R augments the pro-survival effect of BDNF via its interactions with TrkB receptor and exerts an additional BDNF-independent anti-apoptotic effect, both of which contribute to NB chemoresistance. Therefore, the NPY/Y5R pathway may become a novel therapeutic target for patients with refractory NB, thus far an incurable form of this disease. PMID- 25132262 TI - N-terminus-modified Hec1 suppresses tumour growth by interfering with kinetochore microtubule dynamics. AB - Mitotic proteins are attractive targets to develop molecular cancer therapeutics due to the intimate interdependence between cell proliferation and mitosis. In this work, we have explored the therapeutic potential of the kinetochore (KT) protein Hec1 (Highly Expressed in Cancer protein 1) as a molecular target to produce massive chromosome missegregation and cell death in cancer cells. Hec1 is a constituent of the Ndc80 complex, which mediates KT-microtubule (MT) attachments at mitosis and is upregulated in various cancer types. We expressed Hec1 fused with enhanced green fluorescent protein (EGFP) at its N-terminus MT interaction domain in HeLa cells and showed that expression of this modified Hec1, which localized at KTs, blocked cell proliferation and promoted apoptosis in tumour cells. EGFP-Hec1 was extremely potent in tumour cell killing and more efficient than siRNA-induced Hec1 depletion. In striking contrast, normal cells showed no apparent cell proliferation defects or cell death following EGFP-Hec1 expression. Live-cell imaging demonstrated that cancer cell death was associated with massive chromosome missegregation within multipolar spindles after a prolonged mitotic arrest. Moreover, EGFP-Hec1 expression was found to increase KT MT attachment stability, providing a molecular explanation for the abnormal spindle architecture and the cytotoxic activity of this modified protein. Consistent with cell culture data, EGFP-Hec1 expression was found to strongly inhibit tumour growth in a mouse xenograft model by disrupting mitosis and inducing multipolar spindles. Taken together, these findings demonstrate that stimulation of massive chromosome segregation defects can be used as an anti cancer strategy through the activation of mitotic catastrophe after a multipolar mitosis. Importantly, this study represents a clear proof of concept that targeting KT proteins required for proper KT-MT attachment dynamics constitutes a powerful approach in cancer therapy. PMID- 25132263 TI - BRCA1-IRIS inactivation sensitizes ovarian tumors to cisplatin. AB - Ovarian cancer is the first in mortalities among gynecologic cancers in the United States, often due to late diagnosis and/or acquired platinum-resistant recurrences. This study investigates whether BRCA1-IRIS is a novel treatment target for ovarian cancers and in platinum-resistant recurrences. Here we show that more than half of the ovarian cancer samples analyzed showed BRCA1-IRIS and survivin overexpression and lacked nuclear FOXO3a expression. Normal ovarian epithelial cells overexpressing BRCA1-IRIS formed metastasis in mice when injected in the peritoneal cavity, whereas aggressive ovarian cancer cell lines failed to form tumors or metastases in mice when BRCA1-IRIS was silenced in them. We show that BRCA1-IRIS activates two autocrine signaling loops, brain-derived neurotrophic factor/tyrosine kinase B receptor (BDNF/TrkB) and neuregulin 1 (NRG1)/ErbB2. These loops are involved in anoikis resistance and metastasis promotion. These loops operate in several ovarian cancer cell lines, and BRCA1 IRIS silencing or inactivation using a novel inhibitory peptide renders both non functional and promoted cell death. In a mouse xenograft model, BRCA1-IRIS inactivation using this novel inhibitory peptide resulted in significant reduction in ovarian tumor growth. More importantly, this treatment sensitized ovarian tumors to low cisplatin concentrations. Taken together, these data strongly suggest that BRCA1-IRIS and/or BDNF/TrkB and NRG1/ErbB2 could serve as rational therapeutic targets for advanced ovarian cancers. PMID- 25132264 TI - K63-linked ubiquitination of FANCG is required for its association with the Rap80 BRCA1 complex to modulate homologous recombination repair of DNA interstand crosslinks. AB - DNA interstrand crosslinks (ICLs) are extremely deleterious lesions that are repaired by homologous recombination (HR) through coordination of Fanconi anemia (FA) proteins and breast cancer susceptibility gene 1 (BRCA1) product, but the exact role these proteins have remains unclear. Here we report that FANCG was modified by the addition of lysine63-linked polyubiquitin chains (K63Ub) in response to DNA damage. We show that FANCG K63Ub was dispensable for monoubiquitination of FANCD2, but was required for FANCG to interact with the Rap80-BRCA1 (receptor-associated protein 80-BRCA1) complex for subsequent modulation of HR repair of ICLs induced by mitomycin C. Mutation of three lysine residues within FANCG to arginine (K182, K258 and K347, 3KR) reduced FANCG K63Ub modification, as well as its interaction with the Rap80-BRCA1 complex, and therefore impeded HR repair. In addition, we demonstrated that K63Ub-modified FANCG was deubiquitinated by BRCC36 complex in vitro and in vivo. Inhibition of BRCC36 resulted in increased K63Ub modification of FANCG. Taken together, our results identify a new role of FANCG in HR repair of ICL through K63Ub-mediated interaction with the Rap80-BRCA1 complex. PMID- 25132265 TI - Endonuclease G initiates DNA rearrangements at the MLL breakpoint cluster upon replication stress. AB - MLL (myeloid/lymphoid or mixed-lineage leukemia) rearrangements are frequent in therapy-related and childhood acute leukemia, and are associated with poor prognosis. The majority of the rearrangements fall within a 7.3-kb MLL breakpoint cluster region (MLLbcr), particularly in a 0.4-kb hotspot at the intron11-exon12 boundary. The underlying mechanisms are poorly understood, though multiple pathways including early apoptotic signaling, accompanied by high-order DNA fragmentation, have been implicated. We introduced the MLLbcr hotspot in an EGFP based recombination reporter system and demonstrated enhancement of both spontaneous and genotoxic treatment-induced DNA recombination by the MLLbcr in various human cell types. We identified Endonuclease G (EndoG), an apoptotic nuclease, as an essential factor for MLLbcr-specific DNA recombination after induction of replication stress. We provide evidence for replication stress induced nuclear accumulation of EndoG, DNA binding by EndoG as well as cleavage of the chromosomal MLLbcr locus in a manner requiring EndoG. We demonstrate additional dependency of MLLbcr breakage on ATM signaling to histone H2B monoubiquitinase RNF20, involved in chromatin relaxation. Altogether our findings provide a novel mechanism underlying MLLbcr destabilization in the cells of origin of leukemogenesis, with replication stress-activated, EndoG-mediated cleavage at the MLLbcr, which may serve resolution of the stalled forks via recombination repair, however, also permits MLL rearrangements. PMID- 25132267 TI - Anoikis resistance is a critical feature of highly aggressive ovarian cancer cells. AB - High-grade serous ovarian cancer is an aggressive form of epithelial ovarian cancer (EOC), and accounts for the majority of deaths due to EOC. The critical cellular processes and underlying molecular mechanisms that define this malignancy remain poorly understood. Using a syngeneic murine model, we investigated the changes that accompanied the progression to increased aggressiveness induced by in vivo passage of mouse EOC cells. We found that enhanced anoikis resistance was a key cellular process associated with greater aggressiveness and tumorigenicity in vivo. Biochemical studies revealed that the enhanced anoikis resistance was associated with the activation of the Src/Akt/Erk signaling pathway. A higher rate of metabolism and autophagy were also associated with increased anoikis resistance. Blocking these pathways with specific inhibitors and/or genetic modifications significantly increased anoikis in vitro and inhibited tumor development in vivo. In addition, we demonstrated that similar signaling pathways were also involved in a human EOC cell line model. Collectively, our data suggest that anoikis resistance represents a critical and a distinguishing feature underlying the aggressiveness of ovarian cancer cells. PMID- 25132266 TI - MicroRNA regulons in tumor microenvironment. AB - Cancer initiation and progression are defined by the behavior of cancer cells per se and the development of tumor tissues, both of which are modulated by crosstalk between cancer cells and the surrounding microenvironment. Advances in cancer research have highlighted the significance of constant evolution of the tumor microenvironment, leading to tumor formation, metastasis and refractoriness to therapy. MicroRNAs (miRNAs) are small non-coding RNAs that function as major players of posttranscriptional gene regulation in diverse biological processes. They function as both tumor suppressors and promoters in many aspects of the autonomous behavior of cancer cells. Theoretically, dysfunction in the gene regulatory networks of cancer cells is one of the major driving forces for alterations of ostensibly normal surrounding cells. In this context, the core targets of miRNAs, termed miRNA regulons, are currently being expanded to include various modulators of the tumor microenvironment. Recent advances have highlighted two important roles played by miRNAs in the evolution of tumor microenvironments: miRNAs in tumor cells transform the microenvironment via non cell-autonomous mechanisms, and miRNAs in neighboring cells stabilize cancer hallmark traits. These observations epitomize the distal and proximal functions of miRNAs in tumor microenvironments, respectively. Such regulation by miRNAs affects tumor angiogenesis, immune invasion and tumor-stromal interactions. This review summarizes recent findings on the mechanisms of miRNA-mediated regulation of tumor microenvironments, with a perspective on the design of therapeutic interventions. PMID- 25132268 TI - Single-cell gene expression signatures reveal melanoma cell heterogeneity. AB - It is well established that tumours are not homogenous, but comprise cells with differing invasive, proliferative and tumour-initiating potential. A major challenge in cancer research is therefore to develop methods to characterize cell heterogeneity. In melanoma, proliferative and invasive cells are characterized by distinct gene expression profiles and accumulating evidence suggests that cells can alternate between these states through a process called phenotype switching. We have used microfluidic technology to isolate single melanoma cells grown in vitro as monolayers or melanospheres or in vivo as xenografted tumours and analyse the expression profiles of 114 genes that discriminate the proliferative and invasive states by quantitative PCR. Single-cell analysis accurately recapitulates the specific gene expression programmes of melanoma cell lines and defines subpopulations with distinct expression profiles. Cell heterogeneity is augmented when cells are grown as spheres and as xenografted tumours. Correlative analysis identifies gene-regulatory networks and changes in gene expression under different growth conditions. In tumours, subpopulations of cells that express specific invasion and drug resistance markers can be identified amongst which is the pluripotency factor POUF51 (OCT4) whose expression correlates with the tumorigenic potential. We therefore show that single-cell analysis can be used to define and quantify tumour heterogeneity based on detection of cells with specific gene expression profiles. PMID- 25132269 TI - DNA damage response and prostate cancer: defects, regulation and therapeutic implications. AB - DNA damage response (DDR) includes the activation of numerous cellular activities that prevent duplication of DNA lesions and maintain genomic integrity, which is critical for the survival of normal and cancer cells. Specific genes involved in the DDR such as BRCA1/2 and P53 are mutated during prostate cancer progression, while various oncogenic signaling such as Akt and c-Myc are activated, enhancing the replication stress and increasing the genomic instability of cancer cells. These events may render prostate cancer cells particularly sensitive to inhibition of specific DDR pathways, such as PARP in homologous recombination DNA repair and Chk1 in cell cycle checkpoint and DNA repair, creating opportunities for synthetic lethality or synergistic cytotoxicity. Recent reports highlight the critical role of androgen receptor (AR) as a regulator of DDR genes, providing a rationale for combining DNA-damaging agents or targeted DDR inhibitors with hormonal manipulation or AR inhibition as treatment for aggressive disease. The aims of this review are to discuss specific DDR defects in prostate cancer that occur during disease progression, to summarize recent advances in understanding the regulation of DDR in prostate cancer, and to present potential therapeutic opportunities through combinational targeting of the intact components of DDR signaling pathways. PMID- 25132270 TI - CHK1 overexpression in T-cell acute lymphoblastic leukemia is essential for proliferation and survival by preventing excessive replication stress. AB - Checkpoint kinase 1 (CHK1) is a key component of the ATR (ataxia telangiectasia mutated and Rad3-related)-dependent DNA damage response pathway that protect cells from replication stress, a cell intrinsic phenomenon enhanced by oncogenic transformation. Here, we show that CHK1 is overexpressed and hyperactivated in T cell acute lymphoblastic leukemia (T-ALL). CHEK1 mRNA is highly abundant in patients of the proliferative T-ALL subgroup and leukemia cells exhibit constitutively elevated levels of the replication stress marker phospho-RPA32 and the DNA damage marker gammaH2AX. Importantly, pharmacologic inhibition of CHK1 using PF-004777736 or CHK1 short hairpin RNA-mediated silencing impairs T-ALL cell proliferation and viability. CHK1 inactivation results in the accumulation of cells with incompletely replicated DNA, ensuing DNA damage, ATM/CHK2 activation and subsequent ATM- and caspase-3-dependent apoptosis. In contrast to normal thymocytes, primary T-ALL cells are sensitive to therapeutic doses of PF 004777736, even in the presence of stromal or interleukin-7 survival signals. Moreover, CHK1 inhibition significantly delays in vivo growth of xenotransplanted T-ALL tumors. We conclude that CHK1 is critical for T-ALL proliferation and viability by downmodulating replication stress and preventing ATM/caspase-3 dependent cell death. Pharmacologic inhibition of CHK1 may be a promising therapeutic alternative for T-ALL treatment. PMID- 25132271 TI - The dual-acting chemotherapeutic agent Alchemix induces cell death independently of ATM and p53. AB - Topoisomerase inhibitors are in common use as chemotherapeutic agents although they can display reduced efficacy in chemotherapy-resistant tumours, which have inactivated DNA damage response (DDR) genes, such as ATM and TP53. Here, we characterise the cellular response to the dual-acting agent, Alchemix (ALX), which is a modified anthraquinone that functions as a topoisomerase inhibitor as well as an alkylating agent. We show that ALX induces a robust DDR at nano-molar concentrations and this is mediated primarily through ATR- and DNA-PK- but not ATM-dependent pathways, despite DNA double strand breaks being generated after prolonged exposure to the drug. Interestingly, exposure of epithelial tumour cell lines to ALX in vitro resulted in potent activation of the G2/M checkpoint, which after a prolonged arrest, was bypassed allowing cells to progress into mitosis where they ultimately died by mitotic catastrophe. We also observed effective killing of lymphoid tumour cell lines in vitro following exposure to ALX, although, in contrast, this tended to occur via activation of a p53-independent apoptotic pathway. Lastly, we validate the effectiveness of ALX as a chemotherapeutic agent in vivo by demonstrating its ability to cause a significant reduction in tumour cell growth, irrespective of TP53 status, using a mouse leukaemia xenograft model. Taken together, these data demonstrate that ALX, through its dual action as an alkylating agent and topoisomerase inhibitor, represents a novel anti-cancer agent that could be potentially used clinically to treat refractory or relapsed tumours, particularly those harbouring mutations in DDR genes. PMID- 25132272 TI - TGF-beta signaling alters the pattern of liver tumorigenesis induced by Pten inactivation. AB - Hepatocarcinogenesis results from the accumulation of genetic and epigenetic changes in liver cells. A common mechanism through which these alterations induce liver cancer is by deregulating signaling pathways. A number of signaling pathways, including the PI3K/PTEN/AKT and transforming growth factor beta (TGF beta) pathways have been implicated in normal liver development as well as in cancer formation. In this study, we assessed the effect of the TGF-beta signaling pathway on liver tumors induced by phosphatase and tensin homolog (Pten) loss. Inactivation of only the TGF-beta receptor type II, Tgfbr2, in the mouse liver (Tgfbr2(LKO)) had no overt phenotype, while inactivation of Pten alone (Pten(LKO)), resulted in the formation of both hepatocellular carcinomas and cholangiocarcinomas (CC). Interestingly, deletion of both Pten and Tgfbr2 (Pten(LKO);Tgfbr2(LKO)) in the mouse liver resulted in a dramatic shift in tumor type to predominantly CC. Assessment of the PI3K/PTEN/AKT pathway revealed increased phosphorylation of AKT and glycogen synthase kinase 3 beta (GSK-3beta) in both the Pten(LKO) and Pten(LKO);Tgfbr2(LKO) mice, suggesting that this pathway is constitutively active regardless of the status of the TGF-beta signaling pathway. However, phosphorylation of p70 S6 kinase was observed in the liver of all three phenotypes (Tgfbr2(LKO), Pten(LKO), Pten(LKO);Tgfbr2(LKO)) indicating that the loss of Tgfbr2 and/or Pten leads to an increase in this signaling pathway. Analysis of markers of liver progenitor/stem cells revealed that the loss of TGF-beta signaling resulted in increased expression of c-Kit and CD133. Furthermore, in addition to increased c-Kit and CD133, Scf and EpCam expression were also increased in the double knock-out mice. These results suggest that the alteration in tumor types between the Pten(LKO) mice and Pten(LKO);Tgfbr2(LKO) mice is secondary to the altered regulation of stem-cell features induced by the loss of TGF-beta signaling. PMID- 25132275 TI - Desquamative inflammatory vaginitis. AB - Desquamative inflammatory vaginitis (DIV) is an uncommon form of chronic purulent vaginitis. It occurs mainly in Caucasians with a peak occurrence in the perimenopause. Symptoms and signs are nonspecific; DIV is a diagnosis of exclusion, and other causes of purulent vaginitis should be excluded. The main symptoms include purulent discharge, vestibulo-vaginal irritation, and dyspareunia. Examination of vaginal walls shows signs of inflammation with increased erythema and petechiae. Through microscopy (wet mount) of the vaginal secretions, DIV is defined by an increase in inflammatory cells and parabasal epithelial cells (immature squamous cells). Vaginal flora is abnormal and pH is always elevated above 4.5. Although etiology and pathogenesis remain unknown, the favorable response to anti-inflammatory agents suggests that the etiology is immune mediated. Either local vaginal clindamycin or vaginal corticosteroids are adequate treatment. As a chronic condition, maintenance treatment should be considered as relapse is common. PMID- 25132273 TI - Biodegradable poly(ester urethane)urea elastomers with variable amino content for subsequent functionalization with phosphorylcholine. AB - While surface modification is well suited for imparting biomaterials with specific functionality for favorable cell interactions, the modification of degradable polymers would be expected to provide only temporary benefit. Bulk modification by incorporating pendant reactive groups for subsequent functionalization of biodegradable polymers would provide a more enduring approach. Towards this end, a series of biodegradable poly(ester urethane)urea elastomers with variable amino content (PEUU-NH2 polymers) were developed. Carboxylated phosphorycholine was synthesized and conjugated to the PEUU-NH2 polymers for subsequent bulk functionalization to generate PEUU-PC polymers. Synthesis was verified by proton nuclear magnetic resonance, X-ray photoelectron spectroscopy and attenuated total reflection Fourier transform infrared spectroscopy. The impact of amine incorporation and phosphorylcholine conjugation was shown on mechanical, thermal and degradation properties. Water absorption increased with increasing amine content, and further with PC conjugation. In wet conditions, tensile strength and initial modulus generally decreased with increasing hydrophilicity, but remained in the range of 5-30 MPa and 10-20 MPa, respectively. PC conjugation was associated with significantly reduced platelet adhesion in blood contact testing and the inhibition of rat vascular smooth muscle cell proliferation. These biodegradable PEUU-PC elastomers offer attractive properties for applications as non-thrombogenic, biodegradable coatings and for blood-contacting scaffold applications. Further, the PEUU-NH2 base polymers offer the potential to have multiple types of biofunctional groups conjugated onto the backbone to address a variety of design objectives. PMID- 25132277 TI - Surgery of the vulva in vulvar cancer. AB - The standard radical mutilating surgery for the treatment of invasive vulval carcinoma is, today, being replaced by a conservative and individualised approach. Surgical conservative modifications that are currently considered safe, regarding vulval lesion, are separate skin vulval-groin incisions, drawn according to the lesion diameter, and wide local radical excision or partial radical vulvectomy with 1-2 cm of clinically clear surgical margins. Regarding inguinofemoral lymph nodes management, surgical conservative modifications not compromising patient survival are omission of groin lymphadenectomy only when tumour stromal invasion is <= 1 mm, unilateral groin lymphadenectomy only in well lateralised early lesions and total or radical inguinofemoral lymphadenectomy with preservation of femoral fascia when full groin resection is needed. Sentinel lymph node dissection is a promising technique but it should not be routinely employed outside referral centres. Pelvic nodes are better managed by radiation. Locally advanced vulval carcinoma can be managed by ultraradical surgery, exclusive radiotherapy or chemoradiation. PMID- 25132276 TI - Vulvar dermatosis. AB - Vulvar dermatoses are inflammatory conditions responsible for chronic or recurrent itching and soreness. The lesions are either circumscribed to the vulva or associated with extragenital localizations which may help to assess the diagnosis. They should be differentiated from infectious or neoplastic diseases which may have clinical similarities. As opposed to the majority of all dermatoses that have a benign and regular course, lichen sclerosus or lichen planus could exceptionally foster the occurrence of an epithelial cancer precursor which may evolve to squamous cell carcinoma. Topical corticosteroids are the mainstay treatment of vulvar dermatosis. We do not know if the treatment of vulvar lichen sclerosus and vulvar lichen planus prevents squamous cell carcinoma. PMID- 25132274 TI - Curcumin-functionalized silk materials for enhancing adipogenic differentiation of bone marrow-derived human mesenchymal stem cells. AB - Curcumin, a natural phenolic compound derived from the plant Curcuma longa, was physically entrapped and stabilized in silk hydrogel films, and its influence on human bone marrow-derived mesenchymal stem cells (hBMSC) was assessed related to adipogenic differentiation. The presence of curcumin significantly reduced the silk gelation time and changed the porous morphology of gel matrix, but did not change the formation of the silk beta-sheet structure. Based on spectrofluorimetric analysis, curcumin most likely interacted with hydrophobic residues in silk, interacting with the beta-sheet domains formed in the hydrogels. The antioxidant activity of silk film-associated curcumin remained functional over at least one month in both the dry and hydrated state. Negligible curcumin was released from silk hydrogel films over 48 h incubation in aqueous solution. For hBMSC cultured on silk films containing more than 0.25 mg ml(-1) curcumin, cell proliferation was inhibited, while adipogenesis was significantly promoted based on transcripts as well as Oil Red O staining. When hBMSC were cultured in media containing free curcumin, both proliferation and adipogenesis of hBMSC were inhibited when curcumin concentrations exceeded 5 MUM, which is more than 1000 times higher than the level of curcumin released from the films in aqueous solution. Thus, silk film-associated curcumin exhibited different effects on hBMSC proliferation and differentiation compared with curcumin in solution. PMID- 25132278 TI - The effects of an epithelial barrier protective cationic aerosol on allergen induced airway inflammation in asthma: a randomized, placebo-controlled clinical trial. AB - Inhaled cationic airway lining modulator (iCALM) is a cationic aerosol therapy comprised of 1.29% calcium chloride dissolved in 0.9% isotonic saline that enhances the biophysical barrier function of the airway lining fluid and primes the host defense response. It's ability to attenuate bronchitis caused by inhaled particles was investigated using an allergen-inhalation model in a proof-of concept study. In a randomized, double-blind, placebo-controlled cross-over trial of 6 mild atopic steroid-naive asthmatic subjects, 3 doses of iCALM were well tolerated and they attenuated allergen-induced increase in sputum eosinophils, and levels of IL-5, MCP-1 and eotaxin. This study provides an opportunity to investigate the role of enhancing epithelial barrier to decrease airway inflammation provoked by inhaled particles in a variety of airway diseases. PMID- 25132280 TI - Does weight loss in overweight or obese women improve fertility treatment outcomes? A systematic review. AB - This systematic review assessed the effect of weight loss in overweight and/or obese women undergoing assisted reproductive technology (ART) on their subsequent pregnancy outcome. Weight losses achieved by diet and lifestyle changes, very-low energy diets, non-surgical medical interventions and bariatric surgery translated into significantly increased pregnancy rates and/or live birth in overweight and/or obese women undergoing ART in 8 of the 11 studies reviewed. In addition, regularization of the menstrual pattern, a decrease in cancellation rates, an increase in the number of embryos available for transfer, a reduction in the number of ART cycles required to achieve pregnancy and a decrease in miscarriage rates were reported. There were also a number of natural conceptions in five of the six studies that reported this outcome. Non-surgical medical weight loss procedures and bariatric surgery induced the greatest weight losses, but their use, as well as that of very-low-energy diets, for weight loss prior to ART requires careful consideration. While the overall quality of the studies included in this review was poor, these results support the clinical recommendation of advising overweight and/or obese women to lose weight prior to ART. Prospective randomized controlled trials are required to establish efficacious evidence-based guidelines for weight loss interventions in overweight and/or obese women prior to ART treatment. PMID- 25132281 TI - Long-term right ventricular support with a centrifugal ventricular assist device placed in the right atrium. AB - This case series outlines the technique and results of right ventricular assist device (RVAD) support with the off-label use of the centrifugal HeartWare HVAD (HeartWare Inc., Framingham, MA, USA) for long-term support. Four patients in our institution have been implanted with BiVADs, using the Heartware device as the RVAD, and supported for between 117 days and 772 days. Three of the patients have been successfully supported for over 18 months. Three patients have successfully been transplanted and one patient remains on the device, now approaching two years of support. None of the patients have had RVAD device-related complications. PMID- 25132279 TI - Characterization, mutagenesis and mechanistic analysis of an ancient algal sterol C24-methyltransferase: Implications for understanding sterol evolution in the green lineage. AB - Sterol C24-methyltransferases (SMTs) constitute a group of sequence-related proteins that catalyze the pattern of sterol diversity across eukaryotic kingdoms. The only gene for sterol alkylation in green algae was identified and the corresponding catalyst from Chlamydomonas reinhardtii (Cr) was characterized kinetically and for product distributions. The properties of CrSMT were similar to those predicted for an ancient SMT expected to possess broad C3-anchoring requirements for substrate binding and formation of 24beta-methyl/ethyl Delta(25(27))-olefin products typical of primitive organisms. Unnatural Delta(24(25))-sterol substrates, missing a C4beta-angular methyl group involved with binding orientation, convert to product ratios in favor of Delta(24(28)) products. Remodeling the active site to alter the electronics of Try110 (to Leu) results in delayed timing of the hydride migration from methyl attack of the Delta(24)-bond, that thereby produces metabolic switching of product ratios in favor of Delta(25(27))-olefins or impairs the second C1-transfer activity. Incubation of [27-(13)C]lanosterol or [methyl-(2)H3]SAM as co-substrates established the CrSMT catalyzes a sterol methylation pathway by the "algal" Delta(25(27))-olefin route, where methylation proceeds by a conserved SN2 reaction and de-protonation proceeds from the pro-Z methyl group on lanosterol corresponding to C27. This previously unrecognized catalytic competence for an enzyme of sterol biosynthesis, together with phylogenomic analyses, suggest that mutational divergence of a promiscuous SMT produced substrate- and phyla-specific SMT1 (catalyzes first biomethylation) and SMT2 (catalyzes second biomethylation) isoforms in red and green algae, respectively, and in the case of SMT2 selection afforded modification in reaction channeling necessary for the switch in ergosterol (24beta-methyl) biosynthesis to stigmasterol (24alpha-ethyl) biosynthesis during the course of land plant evolution. PMID- 25132282 TI - A randomised clinical trial of 10-day concomitant therapy and standard triple therapy for Helicobacter pylori eradication. AB - BACKGROUND: As a result of increased resistance to antibiotics, Helicobacter pylori eradication rates using standard triple therapy have been declining. AIM: To validate the efficacy and tolerability of a concomitant regimen as a first line treatment for H. pylori infection. METHODS: A total of 348 naive H. pylori infected patients from six hospitals in Korea were randomly assigned to concomitant therapy and standard triple therapy groups. The concomitant regimen consisted of 30 mg of lansoprazole, 1g of amoxicillin, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily for 10 days. The standard triple regimen consisted of 30 mg of lansoprazole, 1g of amoxicillin, and 500 mg of clarithromycin, twice daily for 10 days. RESULTS: Concomitant and standard eradication rates were 78.7% (137/174) vs. 70.7% (123/174) by intention-to-treat (p=0.084) and 88.7% (133/150) vs. 78.4% (120/153) by per-protocol (p=0.016), respectively. The two groups were similar with regard to the incidence of adverse events. CONCLUSIONS: Although 10-day concomitant therapy was validated as a suboptimal treatment option for the treatment of H. pylori infection, this regimen is expected to be a promising starting point in the development of an optimal treatment regimen for H. pylori infection. PMID- 25132283 TI - Is high-viscosity glass-ionomer-cement a successor to amalgam for treating primary molars? AB - OBJECTIVES: To assess and compare the cumulative survival rate of amalgam and atraumatic restorative treatment (ART) restorations in primary molars over 3 years. METHODS: 280 children aged 6-7 years old were enrolled in a cluster randomized controlled clinical trial using a parallel group design covering two treatment groups: conventional restorative treatment with amalgam (CRT) and atraumatic restorative treatment (ART) using a high-viscosity glass-ionomer (HVGIC) Ketac Molar Easymix. Three pedodontists placed 750 restorations (364 amalgam and 386 ART in 126 and 154 children, respectively) which were evaluated at 0.5, 1, 2 and 3 years. The proportional hazard rate regression model with frailty correction, ANOVA and Wald tests, and the Jackknife procedure were applied in analysing the data. RESULTS: The cumulative survival rates over 3 years for all, single- and multiple-surface CRT/amalgam restorations (72.6%, 93.4%, 64.7%, respectively) were no different from those of comparable ART/HVGIC restorations (66.8%; 90.1% and 56.4%, respectively) (p=0.10). Single-surface restorations had higher survival rates than multiple-surface restorations for the both treatment procedures (p<0.0001). A higher proportion of restorations failed because of mechanical reasons (94.8%) than of secondary caries (5.2%). No difference in reasons for restoration failures between all types of amalgam and ART/HVGIC restorations were observed (p=0.24). SIGNIFICANCE: The high-viscosity glass-ionomer used in this study in conjunction with the ART is a viable option for restoring carious dentin lesions in single surfaces in vital primary molars. PMID- 25132284 TI - The determinants of home healthcare robots adoption: an empirical investigation. AB - BACKGROUND: Home healthcare robots promise to make clinical information available at the right place and time, thereby reducing error and increasing safety and quality. However, it has been frequently reported that more than 40% of previous information technology (IT) developments have failed or been abandoned due to the lack of understanding of the sociotechnical aspects of IT. OBJECTIVE: Previous home healthcare robots research has focused on technology development and clinical applications. There has been little discussion of associated social, technical and managerial issues that are arguably of equal importance for robot success. To fill this knowledge gap, this research aims to understand the determinants of home healthcare robots adoption from these aspects by applying technology acceptance theories. METHODS: We employed both qualitative and quantitative methods. The participants were recruited from home healthcare agencies located in the U.S. (n=108), which included both patients and healthcare professionals. We collected data via a survey study to test a research model. RESULTS: The usage intention of home healthcare robots is a function of social influence, performance expectancy, trust, privacy concerns, ethical concerns and facilitating conditions. Among them, social influence is the strongest predictor. Monitoring vital signs and facilitating communication with family and medication reminders are the most preferable tasks and applications for robots. CONCLUSION: Sociotechnical factors play a powerful role in explaining the adoption intention for home healthcare robots. The findings provide insights on how home healthcare service providers and robot designers may improve the success of robot technologies. PMID- 25132285 TI - Comparison of Chromogenic In Situ Hybridization and Fluorescence In Situ Hybridization for the Evaluation of MDM2 Amplification in Adipocytic Tumors. AB - BACKGROUND: Atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) are characterized cytogenetically by a 12q13-15 amplification involving the mouse double minute 2 (MDM2) oncogene. Fluorescence in situ hybridization (FISH) is used frequently to detect this amplification and aid with the diagnosis of these entities, which is difficult by morphology alone. Recently, bright-field in situ hybridization techniques such as chromogenic in situ hybridization (CISH) have been introduced for the determination of MDM2 amplification status. METHODS: The present study compared the results of FISH and CISH for detecting MDM2 amplification in 41 cases of adipocytic tumors. Amplification was defined in both techniques as a MDM2/CEN12 ratio of 2 or greater. RESULTS: Eleven cases showed amplification with both FISH and CISH, and 26 cases showed no amplification with both methods. Two cases had discordant results between CISH and FISH, and two cases were not interpretable by CISH. CONCLUSION: CISH is advantageous for allowing pathologists to evaluate the histologic and molecular alterations occurring simultaneously in a specimen. Moreover, CISH is found to be more cost- and time-efficient when used with automation, and the signals do not quench over time. CISH technique is a reliable alternative to FISH in the evaluation of adipocytic tumors for MDM2 amplification. PMID- 25132286 TI - The Ser680Asn polymorphism in the follicle-stimulating hormone receptor gene is associated with the ovarian response in controlled ovarian hyperstimulation. AB - OBJECTIVE: Polymorphisms in the follicle-stimulating hormone receptor (FSHR) gene are reported to be associated with the ovarian response in controlled ovarian hyperstimulation (COH), although there remains some discordance between studies. Here, using the largest patient sample to date, we evaluated the association of the p.Ser680Asn (S(680)N) polymorphism in the FSHR gene with the outcome of COH. DESIGN: Cohort study. SETTING: Medical academy and hospital. PATIENTS: A total of 1250 infertile Chinese women undergoing IVF/ICIS-ET treatment were included. MEASURES: The association between an FSHR polymorphism (S(680)N) and the ovarian response was analysed. Genotyping was performed by utilizing direct sequencing and the Sequenom MassARRAY iPLEX platform. Follicular fluid oestradiol (E2) and follicle-stimulating hormone (FSH) concentrations were determined using electrochemiluminesence immunoassays. The ovarian response parameters were analysed based on the FSHR genotypes. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for the risk genotypes and alleles. RESULTS: There were linear correlations between the basal FSH level, exogenous gonadotropin consumption, and oocytes retrieved and the Ser680 alleles. Patients in the homozygous SS group demonstrated higher basal FSH levels, required more dosage of exogenous gonadotropin for ovarian stimulation, and had fewer numbers of oocytes retrieved compared with patients in the homozygous NN and heterozygous groups. Logistic regression analysis revealed that the OR of a poor ovarian response for the NS genotype was 1.79 (95% CI 1.28-2.61; P < 0.001), whereas that for the SS genotype was 2.25 (95% CI 1.40-3.58; P < 0.001) after adjusting for age, BMI and basal FSH level. The concentration of E2 in the follicular fluid was significantly higher in subjects with the NN genotype than the SS genotype (772 +/- 545 ng/ml vs. 1299 +/- 504 ng/ml). CONCLUSIONS: Follicle-stimulating hormone receptor gene polymorphism at position 680 is associated with different ovarian responses to controlled ovarian hyperstimulation. PMID- 25132287 TI - Concise review: Exploring miRNAs--toward a better understanding of hematopoiesis. AB - Hematopoiesis is governed by a multidimensional regulatory network involving both intrinsic and extrinsic factors that control self-renewal and differentiation of hematopoietic stem cells (HSCs) through the coordination of influences that affect cell fate. Increasing evidence indicates that microRNAs (miRNAs), short noncoding RNAs of approximately 22 nucleotides, play a central role in orchestrating these regulatory mechanisms to modulate the multiple entities of hematopoietic function in a cell-type specific manner, including self-renewal, lineage commitment, and survival of HSCs as well as their microenvironmental crosstalk. Here, we summarize the current understanding regarding the regulatory effects of miRNA on hematopoietic cells, thus enlightening their role in fine tuning HSC function and hematopoietic homeostasis. PMID- 25132288 TI - Identification of a Plasmodium falciparum inhibitor-2 motif involved in the binding and regulation activity of protein phosphatase type 1. AB - The regulation of Plasmodium falciparum protein phosphatase type 1 (PfPP1) activity remains to be deciphered. Data from homologous eukaryotic type 1 protein phosphatases (PP1) suggest that several protein regulators should be involved in this essential process. One such regulator, named PfI2 based on its primary sequence homology with eukaryotic inhibitor 2 (I2), was recently shown to be able to interact with PfPP1 and to inhibit its phosphatase activity, mainly through the canonical 'RVxF' binding motif. The details of the structural and functional characteristics of this interaction are investigated here. Using NMR spectroscopy, a second site of interaction is suggested to reside between residues D94 and T117 and contains the 'FxxR/KxR/K' binding motif present in other I2 proteins. This site seems to play in concert/synergy with the 'RVxF' motif to bind PP1, because only mutations in both motifs were able to abolish this interaction completely. However, regarding the structure/function relationship, mutation of either the 'RVxF' or 'FxxR/KxR/K' motif is more drastic, because each mutation prevents the capacity of PfI2 to trigger germinal vesicle breakdown in microinjected Xenopus oocytes. This indicates that the tight association of the PfI2 regulator to PP1, mediated by a two-site interaction, is necessary to exert its function. Based on these results, the use of a peptide derived from the 'FxxR/KxR/K' PfI2 motif was investigated for its potential effect on Plasmodium growth. This peptide, fused at its N-terminus to a penetrating sequence, was shown to accumulate specifically in infected erythrocytes and to have an antiplasmodial effect. PMID- 25132289 TI - Papua New Guinea vision-specific quality of life questionnaire: a new patient reported outcome instrument to assess the impact of impaired vision. AB - BACKGROUND: The aim of this study was to develop and validate a new vision specific quality of life (VS QoL) instrument and to assess the impact of vision impairment and eye disease on the quality of life of adults in Papua New Guinea (PNG). DESIGN: This study was designed as community based cross-sectional. PARTICIPANTS: Six hundred fourteen adults aged 18 and above were included in this study. METHODS: Focus groups and interviews guided development of a 41-item instrument. Two valid subscales of the instrument were obtained using pilot data after an iterative item reduction process guided by Rasch-based parameters. The person measures (in logits) of 614 participants were used to assess quality of life using univariate and multivariate regression analysis. MAIN OUTCOME MEASURES: Rasch logits. RESULTS: Rasch analysis confirmed a 17-item instrument containing an 8-item activity limitation subscale and a 9-item well-being subscale. Both subscales were unidimensional and demonstrated good fit statistics, measurement precisions and absence of significant differential item functioning. A consistent deterioration in vision-specific quality of life was independently and significantly associated with levels of vision. Severity of vision impairment and ocular morbidity were independently associated with activity limitation and emotional well-being. Participants with refractive error had lower quality of life score than those with no ocular abnormality but higher score than those with cataract and other eye diseases. CONCLUSIONS: The 17-item PNG-VS QoL instrument is a valid and reliable instrument for the assessment of impact of impaired vision on quality of life in PNG. Vision-specific quality of life was significantly worse among participants who were older and less-educated, had lower income and have had ocular morbidities. PMID- 25132290 TI - Carbon dioxide as a protecting group: highly efficient and selective catalytic access to cyclic cis-diol scaffolds. AB - The efficient and highly selective formation of a wide range of (hetero)cyclic cis-diol scaffolds using aminotriphenolate-based metal catalysts is reported. The key intermediates are cyclic carbonates, which are obtained in high yield and with high levels of diastereo- and chemoselectivity from the parent oxirane precursors and carbon dioxide. Deprotection of the carbonate structures affords synthetically useful cis-diol scaffolds with different ring sizes that incorporate various functional groups. This atom-efficient method allows the simple construction of diol synthons using inexpensive and accessible precursors and green metal catalysts and showcases the use of CO2 as a temporary protecting group. PMID- 25132291 TI - On the International Society of Zoological Sciences: reflections upon a momentous decade. PMID- 25132293 TI - Predators, energetics and fitness drive neonatal reproductive failure in red squirrels. AB - Neonatal reproductive failure should occur when energetic costs of parental investment outweigh fitness benefits. However, little is known about the drivers of neonatal reproductive failure in free-ranging species experiencing continuous natural variation in predator abundance and in the energetic and fitness costs and benefits associated with parental investment. Long-term comprehensive studies are required to better understand how biotic, abiotic and life-history conditions interact to drive occurrences of reproductive failure in the wild. Using 24 years (1987-2011) of reproductive data from a northern boreal population of North American red squirrels in south-western Yukon, we examined the effects of predator abundance, energetics (resource availability, ambient temperature and litter size) and fitness benefits (probability of overwinter juvenile survival and maternal age) on occurrences of neonatal reproductive failure (494/2670 reproductive attempts; 18.5%). Neonatal reproductive failure was driven by a combination of predator abundance, and the energetic and fitness costs and benefits of parental investment. The abundance of mustelids and maternal age was positively related to the occurrence of neonatal reproductive failure. High energy costs associated with a combination of low resource availability and cold ambient temperatures or large litters, corresponded to increased occurrences of neonatal reproductive failure. However, the strength of these relationships was influenced by variation in juvenile overwinter survival (i.e. fitness benefits). We provide evidence that predation pressure is an important driver of neonatal reproductive failure. In addition, we found a trade-off occurs between resource dependent energetic and fitness costs and benefits of raising the current litter to independence. PMID- 25132292 TI - Feasibility of near real-time lesion assessment during radiofrequency catheter ablation in humans using acoustic radiation force impulse imaging. AB - BACKGROUND: Visual confirmation of radiofrequency ablation (RFA) lesions during clinical cardiac ablation procedures could improve procedure efficacy, safety, and efficiency. It was previously shown that acoustic radiation force impulse (ARFI) imaging can identify RFA lesions in vitro and in vivo in an animal model. This is the "first-in-human" feasibility demonstration of intracardiac ARFI imaging of RFA lesions in patients undergoing catheter ablation for atrial flutter (AFL) or atrial fibrillation (AF). METHODS AND RESULTS: Patients scheduled for right atrial (RA) ablation for AFL or left atrial (LA) ablation for drug refractory AF were eligible for imaging. Diastole-gated intracardiac ARFI images were acquired using one of two equipment configurations: (1) a Siemens ACUSON S2000TM ultrasound scanner and 8/10Fr AcuNavTM ultrasound catheter, or (2) a CARTO 3TM integrated Siemens SC2000TM and 10Fr SoundStarTM ultrasound catheter. A total of 11 patients (AFL = 3; AF = 8) were imaged. ARFI images were acquired of ablation target regions, including the RA cavotricuspid isthmus (CTI), and the LA roof, pulmonary vein ostia, posterior wall, posterior mitral valve annulus, and the ridge between the pulmonary vein and LA appendage. ARFI images revealed increased relative myocardial stiffness at ablation catheter contact sites after RFA and at anatomical mapping-tagged RFA treatment sites. CONCLUSIONS: ARFI images from a pilot group of patients undergoing catheter ablation for AFL and AF demonstrate the ability of this technique to identify intra-procedure RFA lesion formation. The results encourage further refinement of ARFI imaging clinical tools and continued investigation in larger clinical trials. PMID- 25132294 TI - Comparison of long-term drug survival and safety of biologic agents in patients with psoriasis vulgaris. AB - BACKGROUND: Drug survival (time to drug discontinuation) has recently emerged as an important parameter reflecting the long-term therapeutic performance in a real life setting. Biologic drug survival in psoriasis is mainly limited by a gradual loss of efficacy over time. Previous studies have been limited by small patient population size and short observation times and yielded discrepant survival times for different biologics. OBJECTIVES: To calculate the long-term drug survival for adalimumab, etanercept, infliximab and ustekinumab in a large cohort of real-life patients with psoriasis vulgaris and to analyse the factors that influence drug survival. PATIENTS AND METHODS: Data were extracted from the prospective registry DERMBIO covering all patients with psoriasis vulgaris treated with biologic agents in the academic centres in Denmark. Drug survival was analysed using the Kaplan-Meier method. The influence of different covariates on drug survival was analysed by Cox regression. RESULTS: Included in the analysis were 1867 treatment series (adalimumab n = 774, etanercept n = 449, infliximab n = 253, ustekinumab n = 391) administered in 1277 patients for up to 10 years. Drug survival was significantly longer for ustekinumab than for anti-tumour necrosis factor (TNF) alpha agents (P < 0.001). Etanercept had the shortest survival time [median survival 30 months, 95% confidence interval (CI) 25.1-34.9] whereas adalimumab and infliximab had comparable survival rates (59 months, 95% CI 45.6-72.4; 44 months, 95% CI 33-54.9, respectively). Survival was longer in men [odds ratio (OR) 1.51, 95% CI 1.31-1.74 vs. women] and in patients who had not previously received any biologic agent (OR 1.24, 95% CI 1.05-1.46). Loss of efficacy accounted for 67% of all drug discontinuations. CONCLUSIONS: Ustekinumab has a significantly longer drug survival than the anti-TNF-alpha agents. Switching from one biologic to another is associated with an impairment of drug survival. Preventing loss of efficacy is a major area of medical need in the biologic therapy of psoriasis and the strategies that improve drug survival should be further investigated. PMID- 25132295 TI - The use of enzyme-coupled magnetic nanoparticles for studying the spectra of unusual substrates of mushroom tyrosinase by direct surface-assisted laser desorption/ionisation and high-resolution electrospray ionisation quadrupole quadrupole-time-of-flight mass spectrometry. AB - RATIONALE: Tyrosinase-coupled magnetic particles (EMPs) were used to demonstrate that resorcinol-containing tyrosinase inhibitors are oxidised by tyrosinase only in the presence of the enzyme's classic substrate. This shows the potential for the application of EMPs as a non-organic matrix for monitoring enzymatic conversion of a novel substrate family directly on-the-spot, principally due to minimal enzyme requirement per analysis. METHODS: Tyrosinase was covalently coupled to core-shell-type silica-coated iron oxide magnetic nanoparticles (EMPs) that were applied as non-organic SALDI matrix suitable for studying low-mass compounds using a classic matrix-assisted laser desorption/ionisation time-of flight (MALDI-TOF) mass spectrometer. Because of the dual function of the EMPs - enzyme host and non-organic matrix - we describe this ionisation method as Enzyme coupled Nanoparticles-Assisted LDI-MS (ENALDI-MS). Supplementary studies of the enzymatic conversion of glabridin and 3-(2,4-dihydroxyphenyl)propionic acid (DHPA) were conducted by high-resolution electrospray ionisation quadrupole quadrupole-time-of-flight mass spectrometry (ESI-QqTOF-MS). RESULTS: The initial experiment involving EMPs as non-organic matrix (ENALDI-MS) showed enzymatic conversion of glabridin, a strong tyrosinase inhibitor, only in the presence of L Tyr, the classic tyrosinase substrate. These findings were evaluated by ESI-QqTOF MS proving that glabridin and DHPA are converted into the corresponding quinones by tyrosinase only in the presence of the auxiliary monophenol or o-diphenol substrates (L-Tyr and catechin, respectively) capable of regenerating the active site of tyrosinase. CONCLUSIONS: EMPs were shown to be useful as a non-organic matrix to monitor enzymatic conversion of the novel tyrosinase substrate family directly on-the-spot with a minimal enzyme consumption (6.5 pmol/spot). Results obtained by ENALDI-MS were fully confirmed by ESI-QqTOF-MS demonstrating that resorcinol-containing tyrosinase inhibitors may be oxidised by the enzyme in the presence of its classic substrates. PMID- 25132296 TI - Cleavage of phosphorus-carbon (P-C) bonds of alpha-amino phosphonates with intramolecular hydrogen migration in the gas phase using electrospray ionization tandem mass spectrometry. AB - RATIONALE: alpha-Amino phosphonates with intrinsic biological activities have been used in a wide variety of applications. Because of the widespread existence of natural organophosphorus compounds containing P-C bonds such as the alpha amino phosphonates, it is important to investigate the gas-phase chemistry of P-C bonds in order to determine their basic properties, which might provide some insights into their biosynthesis and catalytic cleavage. METHODS: Twenty alpha amino phosphonates were successfully synthesized and their fragmentation behavior was systematically investigated using in-solution deuterium labeling in combination with high-resolution Fourier transform ion cyclotron resonance (FTICR) electrospray ionization tandem mass spectrometry. RESULTS: The fragmentation pathways of twenty alpha-amino phosphonates with different chemical structures were systematically studied. In general, P-C bonds could be easily cleaved via a novel intramolecular hydrogen atom migration from the amino group to the phosphoryl group through a five-membered-ring intermediate in the gas phase. A possible mechanism of the rearrangement of alpha-amino phosphonates is proposed. CONCLUSIONS: An interesting intramolecular hydrogen atom migration between the amino and phosphoryl groups was observed with cleavage of the P-C bond in the molecule through a five-membered-ring intermediate. This characteristic fragmentation pathway not only provides some insights into the basic chemistry of compounds with P-C bonds, but could also have some applications in the structural determination of the alpha-amino phosphonate analogues. PMID- 25132298 TI - Gravitational sampling electrospray ionization mass spectrometry for real-time reaction monitoring. AB - RATIONALE: The elucidation of chemical reaction mechanisms has attracted tremendous interest in recent years. Here, gravitational sampling electrospray ionization mass spectrometry (GS-ESI-MS) is used to explore a simple method for the real-time monitoring of chemical and biochemical reactions. METHODS: A sample solution in a stainless steel sample well is directly delivered through a fused silica capillary due to the forces of gravity, capillary action, and electroosmotic flow (EOF). Analyte ions are continuously generated via electrospray ionization from the capillary tip when a high voltage is applied on the sample well. RESULTS: Liquid solutions (<5 MUL) of small organic compounds (e.g., crystal violet) and large biomolecules (e.g., reserpine, angiotensin II, and insulin) were directly analyzed via GS-ESI-MS. In addition, the technique was successfully applied to continuously monitor chemical [e.g. chelation of ethylenediaminetetraacetic acid (EDTA) with copper(II), and addition-elimination of aminophenol and acetic anhydride] and biochemical (e.g., unfolding of cytochrome c) reactions in real time, where chelation complexes, reaction intermediates, and protein conformation changes were observed. CONCLUSIONS: GS ESI-MS is a very simple modification of the ESI technique that does not require sample delivery pumps or nebulizer gases. It is particularly suitable for the analysis of liquid samples and the real-time monitoring of inorganic/organic chemical or biochemical reactions. PMID- 25132297 TI - Low-temperature plasma for compositional depth profiling of crosslinking organic multilayers: comparison with C60 and giant argon gas cluster sources. AB - RATIONALE: For organic electronics, device performance can be affected by interlayer diffusion across interfaces. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) can resolve buried structures with nanometer resolution, but instrument artifacts make this difficult. Low-temperature plasma (LTP) is suggested as a way to prepare artifact-free surfaces for accurate determination of chemical diffusion. METHODS: A model organic layer system consisting of three 1 nm delta layers of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) separated by three 30 nm layers of tris(8-hydroxyquinolinato)aluminum (Alq3) was used to evaluate the effectiveness of LTP etching for the preparation of crater edge surfaces for subsequent compositional depth profile analysis. This was compared with depth profiles obtained using an instrument equipped with an argon cluster sputter source. RESULTS: The quality of the depth profiles was determined by comparing the depth resolutions of the BCP delta layers. The full width at half maximum gave depth resolutions of 6.9 nm and 6.0 nm using LTP, and 6.2 nm and 5.8 nm using argon clusters. In comparison, the 1/e decay length of the trailing edge gave depth resolutions of 2.0 nm and 1.8 nm using LTP, and 3.5 nm and 3.4 nm using argon clusters. CONCLUSIONS: The comparison of the 1/e decay lengths showed that LTP can determine the thickness and composition of the buried structures without instrument artifacts. Although it does suffer from contaminant deposition, LTP was shown to be a viable option for preparing crater edges for a more accurate determination of buried structures. PMID- 25132299 TI - Caution on the use of NBS 30 biotite for hydrogen-isotope measurements with on line high-temperature conversion systems. AB - RATIONALE: The supply of NBS 30 biotite is nearly exhausted. During measurements of NBS 30 and potential replacements, reproducible delta(2)HVSMOW-SLAP values could not be obtained by three laboratories using high-temperature conversion (HTC) systems. The cause of this issue has been investigated using the silver tube technique for hydrogen-isotope measurements of water. METHODS: The delta(2)HVSMOW-SLAP values of NBS 30 biotite, other biotites, muscovites, and kaolinite with different particle sizes, along with IAEA-CH-7 polyethylene, and reference waters and NBS 22 oil that were sealed in silver-tube segments, were measured. The effect of absorbed water on mineral surfaces was investigated with waters both enriched and depleted in (2)H. The quantitative conversion of hydrogen from biotite into gaseous hydrogen as a function of mass and particle size was also investigated. RESULTS: The delta(2)HVSMOW-SLAP values of NBS 30 obtained by three laboratories were as much as 21 0/00 too high compared with the accepted value of -65.7 0/00, determined by conventional off-line measurements. The experiments showed a strong correlation between grain size and the delta(2)HVSMOW-SLAP value of NBS 30 biotite, but not of biotites with lower iron content. The delta(2)HVSMOW-SLAP values of NBS 30 as a function of particle size show a clear trend toward -65.7 0/00 with finer grain size. CONCLUSIONS: Determination of the delta(2)HVSMOW-SLAP values of hydrous minerals and of NBS 30 biotite by on-line HTC systems coupled to isotope-ratio mass spectrometers may be unreliable because hydrogen in this biotite may not be converted quantitatively into molecular hydrogen. Extreme caution in the use and interpretation of delta(2)HVSMOW-SLAP on-line measurements of hydrous minerals is recommended. PMID- 25132300 TI - Interlaboratory assessment of nitrous oxide isotopomer analysis by isotope ratio mass spectrometry and laser spectroscopy: current status and perspectives. AB - RATIONALE: In recent years, research and applications of the N2O site-specific nitrogen isotope composition have advanced, reflecting awareness of the contribution of N2O to the anthropogenic greenhouse effect, and leading to significant progress in instrument development. Further dissemination of N2O isotopomer analysis, however, is hampered by a lack of internationally agreed gaseous N2O reference materials and an uncertain compatibility of different laboratories and analytical techniques. METHODS: In a first comparison approach, eleven laboratories were each provided with N2O at tropospheric mole fractions (target gas T) and two reference gases (REF1 and REF2). The laboratories analysed all gases, applying their specific analytical routines. Compatibility of laboratories was assessed based on N2O isotopocule data for T, REF1 and REF2. Results for T were then standardised using REF1 and REF2 to evaluate the potential of N2O reference materials for improving compatibility between laboratories. RESULTS: Compatibility between laboratories depended on the analytical technique: isotope ratio mass spectrometry (IRMS) results showed better compatibility for delta(15)N values, while the performance of laser spectroscopy was superior with respect to N2O site preference. This comparison, however, is restricted by the small number of participating laboratories applying laser spectroscopy. Offset and two-point calibration correction of the N2O isotopomer data significantly improved the consistency of position-dependent nitrogen isotope data while the effect on delta(15)N values was only minor. CONCLUSIONS: The study reveals that for future research on N2O isotopocules, standardisation against N2O reference material is essential to improve interlaboratory compatibility. For atmospheric monitoring activities, we suggest N2O in whole air as a unifying scale anchor. PMID- 25132301 TI - Fragmentation of negative ions from N-linked carbohydrates: part 6. Glycans containing one N-acetylglucosamine in the core. AB - RATIONALE: Negative ion collision-induced dissociation (CID) spectra of N-glycans contain many diagnostic ions that provide more structural information than positive ion spectra. EndoH or endoS release of glycans from glycoproteins, as used by many investigators, cleaves glycans between the GlcNAc residues of the chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue. However, their negative ion CID spectra do not appear to have been studied in detail. This paper examines the CID and ion mobility properties of these endoH released glycans to determine if the missing GlcNAc influences the production of diagnostic fragment ions. METHODS: N-Glycans were released from ribonuclease B, ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from IgG with endoS to produce biantennary complex glycans, all missing the reducing terminal GlcNAc residue. Negative ion CID and travelling wave ion mobility spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray sample introduction. RESULTS: The majority of glycans yielded CID spectra exhibiting the same diagnostic fragments, which were equivalently informative, as the fully released structures. However, the ability of ion mobility to separate isomers was generally found to be inferior to its use with the full glycans despite the smaller nature of the compounds. The exception was the partial resolution of a pair of biantennary monogalactosylated glycans from IgG where, as chloride adducts, slight separation of the isomers was observed. CONCLUSIONS: The results show that the CID spectra of endoH- and endoS-released glycans are as useful as the corresponding spectra of the intact glycans (as released by PNGase F) in providing structural information on N-glycans. PMID- 25132302 TI - Transformation of gas-phase amino acid clusters to dipeptides: a nice approach to demonstrate the formation of prebiotic peptides. AB - RATIONALE: Exploring prebiotic developments is a fascinating area of research which is continually drawing the attention of the scientific community. It is probable that first the biomolecules were formed and then they became aggregated to generate life. Formation of one such biomolecules (peptide ions) is shown in the present experiments. METHODS: All amino acid solutions for recording mass spectra were prepared in 3:6.9:0.1 (v/v/v) acetonitrile/water/formic acid at a concentration of 50 MUM. The studies were performed using a Bruker MicroTOF QII mass spectrometer. Before carrying out experiments in the collision cell, atmospheric pressure in-source fragmentations were also performed. The formation of different chemical species was detected with high-resolution mass spectrometry. RESULTS: Here, we show experimentally the formation of amino acid cluster ions of varied populations, when a solution of an amino acid was injected into an electrospray ionization quadrupole time-of-flight (ESI-QTOF) mass spectrometer. During in-source fragmentation/collision cell fragmentation, the non-covalent interaction between two identical amino acids forms either the [M2 + H](+) dimer cluster ion and/or the [M2 + K](+) adduct ion which, by elimination of one molecule of water, form the covalent linked dipeptide. CONCLUSIONS: After the formation of the amino acid cluster, it was established that the creation of the dipeptides, by a covalent bond resulting from the loss of a water molecule, was the initial step towards the formation of the primordial peptides. PMID- 25132303 TI - Modification of a gas chromatography/atmospheric pressure chemical ionisation time-of-flight mass spectrometer as an alternative to automated atmospheric pressure solids analysis probe. AB - RATIONALE: The atmospheric pressure solids analysis probe (ASAP) has been successfully introduced into laboratories as a routine analytical tool but the technique is labour-intensive and is not easily automated. This paper describes the modifications made to an existing atmospheric pressure gas chromatography (APGC) system to enable the automated analysis of samples that would have otherwise been analysed by ASAP. METHODS: Liquid samples were injected into a 1 m piece of fused silica guard column using a standard split/splitless gas chromatography (GC) inlet, oven and autosampler. A novel timing delay circuit was developed and integrated into the system to control acquisition start times and a bespoke heating block/calibrant delivery system was used to transport either the calibration or reference compound into the ionisation source. RESULTS: The modified system has allowed the successful analysis of those samples requiring ASAP to be carried out in a fully automated manner using APGc. The analysis is rapid and can be carried out in less than 2 min. The results obtained are directly comparable with those obtained by ASAP. A typical mass accuracy of better than 5 mm/z units was achieved, allowing the molecules to be identified based on their elemental formulae. CONCLUSIONS: An existing APGC system has been successfully modified and is suitable for the automatic analysis of samples normally analysed by ASAP. The APGC instrument incorporates the use of a novel reference compound and delivery system which allows accurate mass measurements to be performed. This and the other modifications described have allowed the technique to be incorporated into an existing suite of mass spectrometry-based experiments for use in the characterisation of organic molecules. PMID- 25132304 TI - Lingual tonsil hypertrophy diagnosed by post-mortem computed tomography in a difficult airway case. PMID- 25132305 TI - Of low back pain and moxibustion. PMID- 25132306 TI - "Moving forward: outlining the plan"-dean's report of the Faculty of Pain Medicine of the Australian and New Zealand College of Anaesthetists. PMID- 25132307 TI - Report of the NIH Task Force on research standards for chronic low back pain. AB - OBJECTIVE: Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific, and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. DESIGN: Expert panel and preliminary evaluation of key recommendations. METHODS: The NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel developed a 3-stage process, each with a 2-day meeting. RESULTS: The panel recommended using 2 questions to define cLBP; classifying cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimal data set to describe research subjects (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. CONCLUSION: The RTF believes these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. We expect the RTF recommendations will become a dynamic document, and undergo continual improvement. PERSPECTIVE: A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. PMID- 25132310 TI - Fungal phytases: characteristics and amelioration of nutritional quality and growth of non-ruminants. AB - Fungal phytases are histidine acid phosphatases, a subclass of acid phosphatases, which catalyse the hydrolysis of phytic acid resulting in the release of phosphate moieties and thus mitigate its antinutritional properties. The supplementation of feed with phytases increases the bioavailability of phosphorus and minerals in non-ruminant animals and reduces the phosphorus pollution due to phosphorus excretion in the areas of intensive livestock production. Although phytases are reported in plants, animals and micro-organisms, fungal sources are used extensively for the production of phytases on a commercial scale. Phytases have been produced by fungi in both solid-state fermentation (SSF) and submerged fermentation (SmF). The fungal phytases are high molecular weight proteins ranging from 35 to 500 kDa. They are optimally active within pH and temperature ranges between 4.5 and 6.0, and 45 and 70 degrees C respectively. Phytate degradation leads to amelioration in the nutritional status of foods and feeds by improving the availability of minerals, phosphorus and proteins in non-ruminant animals and human beings and thus mitigates the environmental phosphorus pollution. Our article focuses on the role of fungal phytases in improving nutritional value of foods and feeds with concomitant increase in growth of non ruminant animals and mitigating environmental phosphorus pollution. PMID- 25132308 TI - Characterizing heat-sensitization responses in suspended moxibustion with high density EEG. AB - OBJECTIVE: We have reported "heat-sensitization" responses during suspended moxibustion, whose occurrence is associated with significantly better therapeutic effects. The present study aimed to characterize the electrophysiological features of this interesting phenomenon with high-density electroencephalography (EEG). METHODS: We performed EEG recording in a group of patients with chronic low back pain before, during, and after moxibustion treatment at DU3. RESULTS: 12 out of 25 subjects experienced strong heat-sensitization during moxibustion, which was accompanied by increased power spectral densities (PSDs) at the theta, alpha, and beta frequency bands. The scalp topographies of averaged power indicated that the theta and beta PSD changes were most obvious in fronto-central regions, whereas those of the alpha band were more global. In addition, nonsensitized and sensitized groups showed distinct activity patterns, with heat sensitization inducing increased phase coherence at the theta and beta ranges. CONCLUSIONS: These data were the first objective evidence of heat-sensitization responses during suspended moxibustion, which were characterized by widespread oscillatory changes in scalp EEG. PMID- 25132311 TI - Graphene/polydopamine-modified polytetrafluoroethylene microtube for the sensitive determination of three active components in Fructus Psoraleae by online solid-phase microextraction with high-performance liquid chromatography. AB - Determination of bioactive compounds in traditional Chinese medicines and biological samples is usually interfered with by coexisting components in matrices. In this work, we prepared novel multilayer functional graphene/polydopamine-modified polytetrafluoroethylene microtube for selective solid-phase microextraction of three bioactive compounds in Fructus Psoraleae. Functional graphene/polydopamine-modified polytetrafluoroethylene microtube showed good extraction efficiency toward bavachin, isobavachalcone, and bavachinin; enrichment from 357- to 737-fold was obtained for these compounds. For qualitative analysis, an online solid-phase microextraction with high performance liquid chromatography method was developed, which showed low limits of detection of 0.02 ng/mL by using UV detection, which is significantly more sensitive than previously reported methods. The proposed method has been used to determine bavachin, isobavachalcone, and bavachinin in Fructus Psoraleae, the contents of three compounds were quantified to be 64.0, 324.0, and 384.5 MUg/g; recoveries were 93.4-101.1%. The proposed method has also been applied to determine bavachin, isobavachalcone, and bavachinin in rat plasma samples after oral administration of Fructus Psoraleae. PMID- 25132312 TI - Designing the nanobiointerface of fluorescent nanodiamonds: highly selective targeting of glioma cancer cells. AB - Core-shell nanoparticles based on fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed for background-free near-infrared imaging of cancer cells. The particles showed excellent colloidal stability in buffers and culture media. After conjugation with a cyclic RGD peptide they selectively targeted integrin alphavbeta3 receptors on glioblastoma cells with high internalization efficacy. PMID- 25132313 TI - Novel endoscopic diagnosis for bladder cancer. AB - Advances in endoscopic imaging technology may improve sensitivity for the detection of bladder cancer and provide a more complete understanding of the urothelial landscape, and it also may lead to improved short-term and long-term cancer control. Fluorescence cystoscopy requires intravesical administration of a photosensitizing agent (5-aminolevulinic acid or hexaminolevulinate), and imaging with a blue-light endoscopy system demonstrably improves the detection of papillary and flat bladder lesions compared with conventional white-light cystoscopy. Prospective phase 3 clinical trials have demonstrated improved diagnostic ability, enhanced tumor resection, and a small but significant reduction in recurrence-free survival. Optical coherence tomography delineates subsurface microarchitecture information about bladder lesions in real time and has the ability to discriminate between noninvasive and invasive cancers. Narrow band imaging may augment white-light cystoscopy by providing increased contrast between normal and abnormal tissue on the basis of neovascularity. Confocal laser endoscopy has been applied to the urinary tract using thinner probes adapted from use in gastrointestinal malignancies and provides exquisite images at microscopic resolution. More technology is on the horizon that may further enhance our ability to detect and accurately stage bladder tumors and distinguish benign from malignant or dysplastic lesions. PMID- 25132314 TI - Predictors of unmet needs and psychological distress in adolescent and young adult siblings of people diagnosed with cancer. AB - PURPOSE: Predictors of psychological distress and unmet needs amongst adolescents and young adults (AYAs) who have a brother or sister diagnosed with cancer were examined. METHODS: There were 106 AYAs (12-24 years old) who completed questionnaires covering demographics, psychological distress (Kessler 10), unmet needs (Sibling Cancer Needs Instrument) and family relationships (Family Relationship Index; Adult Sibling Relationship Questionnaire; Sibling Perception Questionnaire (SPQ)). Three models were analysed (demographic variables, cancer specific variables and family functioning variables) using multiple linear regression to determine the role of the variables in predicting psychological distress and unmet needs. RESULTS: Unmet needs were higher for AYA siblings when treatment was current or a relapse had occurred. Higher scores on the SPQ Interpersonal subscale indicating a perceived decrease in the quality of relationships with parents and others were associated with higher levels of distress and unmet needs. The age and gender of the AYA sibling, whether it was their brother or sister who was diagnosed with cancer, the age difference between them, the number of parents living with the AYA sibling, parental birth country, time since diagnosis, Family Relationship Index, Adult Sibling Relationship Questionnaire and the SPQ-Communication subscale did not significantly impact outcome variables. CONCLUSIONS: These results highlight the variables that can assist in identifying AYA siblings of cancer patients who are at risk and have a greater need for psychosocial assistance. Variables that may be associated with increased distress and unmet needs are reported to assist with future research. The results are also useful in informing the development of targeted psychosocial support for AYA siblings of cancer patients. PMID- 25132315 TI - LC-MS/MS analysis of Gegen Qinlian Decoction and its pharmacokinetics after oral administration to rats. AB - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of 12 constituents of Gegen Qinlian Decoction (GQD), namely puerarin, daidzein, baicalin, wogonoside, wogonin, liquiritin, liquiritigenin, berberine, jatrorrhizine, palmatine, coptisine and glycyrrhetic acid, in rat plasma. The plasma samples were spiked with the internal standard (IS) carbamazepine acidified with HCl and extracted by liquid-liquid extraction with ethyl acetate. Chromatographic separation was achieved on a Shiseido Capcell PAK C18 column utilizing a gradient elution profile and a mobile phase consisting of (A) 0.1% formic acid in water and (B) acetonitrile. Detection was performed in the multiple reaction monitoring mode using electrospray ionization in the positive ion mode at a flow rate of 0.3 mL/min and a run time of 8 min. All of the calibration curves gave good linearity (r > 0.9930) over the concentration range from 0.6-360 to 16.2-9720 ng/mL for all components. The intra- and inter-day precisions were <15.0% in terms of the relative standard deviation, and the accuracies were within +/-13.7% in terms of the relative error. The method was successfully applied to investigate the pharmacokinetics of the major active compounds of Gegen Qinlian Decoction after its oral administration to rats. PMID- 25132316 TI - Synaptic plasticity under learning challenge. AB - Memory formation requires changes in neuronal networks connectivity based on modifications in strength and number of synapses. The mechanisms driving these changes have been intensively studied, but mostly under naive conditions, i.e. in animals that have not been cognitively challenged. Better characterization of synaptic requirements supporting memory formation can emerge from studies focusing on synaptic changes in memory-encoding structures while or after the animal model is cognitively challenged. Here, with this concept in mind, we review the literature describing structural, functional and molecular alterations developing in the hippocampus when animals are asked to form memories. We also briefly discuss the interest of this approach for disclosing pathological mechanisms in memory disorders, which might otherwise not be observed in naive conditions. PMID- 25132317 TI - APOE epsilon4 allele is associated with worse performance in memory dimensions of the mini-mental state examination: the Bambui Cohort Study of Aging. AB - OBJECTIVE: This study aimed to investigate the correlation between apolipoprotein E (APOE) epsilon4 and the mini-mental state examination (MMSE) dimension in an elderly population, using baseline data from the Bambui (Brazil) Cohort Study of Aging. DESIGN: We conducted a community-based cross-sectional study. SETTING: The study took place at Bambui city, Minas Gerais State, Southeast Brazil. PARTICIPANTS: A total of 1408 (87.7%) cohort participants had complete information on the MMSE and health measures. MEASUREMENTS: The association between each of five dimensions (concentration, language/praxis, orientation, attention, and memory) underlying the MMSE and APOE epsilon4 allele was assessed using multivariate linear regression models. Potential confounding variables included sociodemographic factors and selected biomarkers. RESULTS: The main finding is a strong negative association between the presence of APOE epsilon4 allele and memory dimension in the MMSE (fully adjusted beta coefficient = -0.14; 95% confidence interval: -0.27 to -0.04; p = 0.016). No other cognitive dimensions showed significant associations with the APOE epsilon4 allele. CONCLUSION: This study is the first to investigate the association between dimensions of the MMSE, obtained from principal component analysis and APOE epsilon4 carrier status in community-dwelling older adults taking into account a range of potential confounding factors. We found a strong negative association between the presence of APOE epsilon4 allele and scores on memory dimension of the MMSE, but no effect on other dimensions. Our results reinforce previous data on the literature that APOE epsilon4 allele has a significant effect on cognitive performance that can be detected even in screening tests, such as the MMSE. PMID- 25132318 TI - Depression, dementia and cognition in older people. PMID- 25132319 TI - Association between inflammatory markers and frailty in institutionalized older men. AB - OBJECTIVES: To determine whether higher serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and high sensitivity C-reactive protein (CRP) were associated with frailty in the older institutionalized men. PARTICIPANTS: The study enrolled 386 residents from a veterans care home in northern Taiwan in 2007. All participants were men. Residents younger than 65 years or with acute illness were excluded. METHODS: Frailty status was determined based on the frailty phenotype (indicators include weight loss, exhaustion, and low grip strength, slow walking speed). Participants with 3 or more of the indicators were defined as frail, with 1 or 2 as intermediate frail, with no as non-frail. Serum IL-6, TNF-alpha, and hsCRP levels were measured using enzyme linked immunosorbent assay and modeled as tertile for severely skewed distributions. RESULTS: The mean age of the participants was 81.5+/-4.9 years. The percentages of frail were 33.2%, intermediate frail 59.1% and nonfrail 7.8%. Higher IL-6 level was positively associated with the frail status. Adjusting for age, body mass index, smoking status, and comorbid conditions, serum IL-6 showed significant trend across frailty categories (P=0.03 [95% CI 1.40-5.24]). No significant associations of TNF-alpha, and CRP level with frailty were observed. An IL-6 level of 1.79pg/mL had the optimal predictive value for frailty, with an area under the receiver operating characteristic (ROC) curve of 0.66 (P=0.01 [95% CI 0.53-0.78]). CONCLUSION: Higher serum levels of IL-6 were associated with frailty status in the older institutionalized men with multiple comorbidities. PMID- 25132321 TI - An octadentate bifunctional chelating agent for the development of stable zirconium-89 based molecular imaging probes. AB - (89)Zr-based imaging agents hold great promise as novel radio-tracers in nuclear medicine. However, insufficient stability of currently used radiometal complexes in vivo is a safety concern for clinical applications. We herein report the first octadentate bifunctional chelating agent for the development of (89)Zr-labelled (bio)conjugates with improved stability. PMID- 25132320 TI - Accuracy of two continuous glucose monitoring systems: a head-to-head comparison under clinical research centre and daily life conditions. AB - AIMS: To assess the accuracy and reliability of the two most widely used continuous glucose monitoring (CGM) systems. METHODS: We studied the Dexcom(r)G4 Platinum (DG4P; Dexcom, San Diego, CA, USA) and Medtronic Paradigm Veo Enlite system (ENL; Medtronic, Northridge, CA, USA) CGM systems, in 24 patients with type 1 diabetes. The CGM systems were tested during 6-day home use and a nested 6 h clinical research centre (CRC) visit. During the CRC visit, frequent venous blood glucose samples were used as reference while patients received a meal with an increased insulin bolus to induce an aggravated postprandial glucose nadir. At home, patients performed at least six reference capillary blood measurements per day. A Wilcoxon signed-rank test was performed using all data points >=15 min apart. RESULTS: The overall mean absolute relative difference (MARD) value [standard deviation (s.d.)] measured at the CRC was 13.6 (11.0)% for the DG4P and 16.6 (13.5)% for the ENL [p < 0.0002, confidence interval of difference (CI Delta) 1.7-4.3%, n = 530]. The overall MARD assessed at home was 12.2 (12.0)% for the DG4P and 19.9 (20.5)% for the ENL (p < 0.0001, CI Delta = 5.8-8.7%, n = 839). During the CRC visit, the MARD in the hypoglycaemic range [<=3.9 mmol/l (70 mg/dl)], was 17.6 (12.2)% for the DG4P and 24.6 (18.8)% for the ENL (p = 0.005, CI Delta 3.1-10.7%, n = 117). Both sensors showed higher MARD values during hypoglycaemia than during euglycaemia [3.9-10 mmol/l (70-180 mg/dl)]: for the DG4P 17.6 versus 13.0% and for the ENL 24.6 versus 14.2%. CONCLUSIONS: During circumstances of intended use, including both a CRC and home phase, the ENL was noticeably less accurate than the DG4P sensor. Both sensors showed lower accuracy in the hypoglycaemic range. The DG4P was less affected by this negative effect of hypoglycaemia on sensor accuracy than was the ENL. PMID- 25132322 TI - Three-dimensional characterization of noble-metal nanoparticles and their assemblies by electron tomography. AB - New developments in the field of nanomaterials drive the need for quantitative characterization techniques that yield information down to the atomic scale. In this Review, we focus on the three-dimensional investigations of metal nanoparticles and their assemblies by electron tomography. This technique has become a versatile tool to understand the connection between the properties and structure or composition of nanomaterials. The different steps of an electron tomography experiment are discussed and we show how quantitative three dimensional information can be obtained even at the atomic scale. PMID- 25132323 TI - Avian influenza H9N2 subtype in Poland--characterization of the isolates and evidence of concomitant infections. AB - In April/May 2013, four outbreaks of avian influenza virus (AIV) infections caused by H9N2 subtype were diagnosed in Poland in fattening turkey flocks exhibiting a drop in feed and water intake, depression, respiratory signs and mortality. The subsequent serological survey carried out on samples collected between June 2012 and September 2013 from 92 poultry flocks detected positive sera in two additional meat turkey flocks located in the same province. The analysis of amino acids in the haemagglutinin and neuraminidase glycoproteins revealed that the detected H9N2 viruses possessed molecular profiles suggestive of low pathogenicity, avian-like SAalpha2,3 receptor specificity and adaptation to domestic poultry. Phylogenetic studies showed that these H9N2 AIVs grouped within the Eurasian clade of wild bird-origin AIVs and had no relationship with H9N2 AIV circulating in poultry in the Middle East and Far East Asia over the past decade. Experimentally infected SPF chickens with the index-case H9N2 virus remained healthy throughout the experiment. On the other hand, ten 3-week-old commercial turkeys infected via the oculonasal route showed respiratory signs and mortality (2/10 birds). Additional diagnostic tests demonstrated the consistent presence of DNA/RNA of Ornithobacterium rhinotracheale, Bordetella avium and, less frequently, of astro-, rota-, reo-, parvo- and adenoviruses in turkeys both from field outbreaks and laboratory experiment. Although no microbiological culture was performed, we speculate that these secondary pathogens could play a role in the pathogenicity of the current H9N2 infections. PMID- 25132324 TI - Challenges and potential solutions to educating learners about pediatric complex care. AB - OBJECTIVE: To identify existing challenges and potential strategies for providing complex care training to future pediatricians from a national group of educators. METHODS: Data were collected from pediatric educators involved in complex care at the Pediatric Educational Excellence Across the Continuum national meeting. Participants completed an anonymous 15-item survey adapted from the Association of American Medical Colleges (AAMC) Best Practices for Better Care initiative and participated in a focus group to understand the challenges and potential solutions to pediatric complex care education. Data were analyzed using grounded theory. RESULTS: Of the 15 participants, 9 (60%) were in educational leadership positions. All participants provided care to children with medical complexity (CMC), although 80% (n = 12) reported no formal training. Thematic analysis revealed learners' challenges in 2 domains: 1) a lack of ownership for the patient because of decreased continuity, decision-making authority, and autonomy, as a result of the multitude of care providers and parents' distrust; and 2) a sense of being overwhelmed as a result of lack of preparedness and disruptions in work flow. Participants suggested 3 mitigating strategies: being candid about the difficulties of complex care, discussing the social mandate to care for CMC, and cultivating humility among learners. CONCLUSIONS: Residency education must prepare pediatricians to care for all children, regardless of disease. Training in complex care involves redefining the physician's role so that they are better equipped to participate in collaboration, empathy and advocacy with CMC. This study is the first to identify specific challenges and offer potential solutions to help establish training guidelines. PMID- 25132325 TI - Lymphocytes subsets reference values in childhood. AB - Immunophenotyping of blood lymphocyte subsets and activation markers is a basic tool in the diagnostic process of primary immunodeficiency diseases, its use becoming more and more widespread as the knowledge about these illnesses increases. However, the availability of reliable reference values, which need to be age-matched for the pediatric population, is a pre-requisite for the reliable interpretation of immunophenotyping data. Aim of this study is to analyze the lymphocyte subsets and activation markers distribution in children aged 0-18 years referring to the University Hospital of Padova and to create age-matched reference values expressed by percentiles, thus providing a valuable guideline for the interpretation of the immunophenotype. PMID- 25132327 TI - An EBP mentor and unit-based EBP team: a strategy for successful implementation of a practice change to reduce catheter-associated urinary tract infections. PMID- 25132326 TI - Melatonin treatment further improves adipose-derived mesenchymal stem cell therapy for acute interstitial cystitis in rat. AB - This study tests the hypothesis that combined melatonin and adipose-derived mesenchymal stem cell (ADMSC, 1.2 * 10(6) given intravenously) treatment offer superior protection against cyclophosphamide (CYP 150 mg/kg)-induced acute interstitial cystitis (AIC) in rats. Male adult Sprague-Dawley rats were treated as follows: sham controls, AIC alone, AIC + melatonin, AIC + ADMSC, and AIC + melatonin +ADMSC. When melatonin was used, it was given as follows: 20 mg/kg at 30 min after CYP and 50 mg/kg at 6 and 18 hr after CYP. Twenty-four-hour urine volume, urine albumin level, and severity of hematuria were highest in AIC rats and lowest in the controls; likewise urine volume was higher in AIC + melatonin rats than in AIC + ADMSC and AIC + melatonin + ADMSC treated rats; in all cases, P < 0.001. The numbers of CD14+, CD74+, CD68+, MIP+, Cox-2+, substance P+, cells and protein expression of IL-6, IL-12, RANTES, TNF-alpha, NF-kappaB, MMP-9, iNOS (i.e. inflammatory biomarkers), glycosaminoglycan level, expression of oxidized protein, and protein expression of reactive oxygen species (NOX-1, NOX-2, NOX-4) in the bladder tissue exhibited an identical pattern compared with that of hematuria among the five groups (all P < 0.0001). The integrity of epithelial layer and area of collagen deposition displayed an opposite pattern compared to that of hematuria among all groups (P < 0.0001). The cellular expressions of antioxidants (GR, GPx, HO-1, NQO 1) showed a significant progressive increase form controls to AIC + melatonin + ADMSC (all P < 0.0001). Combined regimen of melatonin and ADMSC was superior to either alone in protecting against CYP induced AIC. PMID- 25132328 TI - Development of category-based induction and semantic knowledge. AB - Category-based induction is a hallmark of mature cognition; however, little is known about its origins. This study evaluated the hypothesis that category-based induction is related to semantic development. Computational studies suggest that early on there is little differentiation among concepts, but learning and development lead to increased differentiation based on taxonomic relatedness. This study reports findings from a new task aimed to (a) examine this putative increase in semantic differentiation and (b) test whether individual differences in semantic differentiation are related to category-based induction in 4- to 7 year-old children (N = 85). The results provide the first empirical evidence of an age-related increase in differentiation of representations of animal concepts and suggest that category-based induction is related to increased semantic differentiation. PMID- 25132329 TI - TPO concentrations and response to romiplostim. PMID- 25132330 TI - Comparison of hemodynamic performance of the balloon-expandable SAPIEN 3 versus SAPIEN XT transcatheter valve. AB - The SAPIEN 3 valve (S3V) is a new-generation transcatheter valve with enhanced anti-paravalvular leak properties, but no data comparing with earlier transcatheter valve systems are available. We aimed to compare the hemodynamic performance of the S3V and the SAPIEN XT valve (SXTV) in a case-matched study with echo core laboratory analysis. A total of 27 patients who underwent transcatheter aortic valve replacement (TAVR) with the S3V were matched for prosthesis size (26 mm), aortic annulus area, and mean diameter measured by computed tomography, left ventricular ejection fraction, body surface area, and body mass index with 50 patients treated with the SXTV. The prosthesis size was determined by oversizing of 1% to 15% of annulus area. Doppler echocardiographic images collected at baseline and 1-month follow-up were analyzed in a central echocardiography core laboratory. The need for postdilation was higher in the SXTV group (20% vs 4%, p=0.047), and mean residual gradient and effective orifice area were similar in both groups (p>0.05). The incidence of paravalvular aortic regurgitation was greater with the SXTV (>=mild: 42%, moderate: 8%) than with the S3V (>=mild: 7%, moderate: 0%; p=0.002 for >=mild vs SXTV). The implantation of an S3V was the only factor associated with trace or no paravalvular leak after TAVR (p=0.007). In conclusion, TAVR with the S3V was associated with a very low rate of paravalvular leaks and need for balloon postdilation, much lower than that observed with the earlier generation of balloon-expandable valve (SXTV). The confirmation of these results in a larger cohort of patients will represent a major step forward in using transcatheter valves for the treatment of aortic stenosis. PMID- 25132331 TI - Characteristics of trabeculated myocardium burden in young and apparently healthy adults. AB - Increased myocardial trabeculations define noncompaction cardiomyopathy (NCC). Imaging advancements have led to increasingly common identification of prominent trabeculations with unknown implications. We quantified and determined the impact of trabeculations' burden on cardiac function and stretch in a population of healthy young adults. One hundred adults aged 18 to 35 years (28+/-4 years, 55% women) without known cardiovascular disease were prospectively studied by cardiovascular magnetic resonance. Left ventricular (LV) volumes, segmental function, and ejection fraction (EF) and left atrial volumes were determined. Thickness and area of trabeculated (T) and dense (D) myocardium were measured for each standardized LV segment. N-terminal pro-brain natriuretic peptide (Nt-pro BNP) was measured. Eighteen percent of the subjects had >=1 positive traditional criteria for NCC, and 11% meet new proposed NCC cardiovascular magnetic resonance criteria. Trabeculated over dense myocardium ratio (T/D) ratios were uniformly greater at end-diastole versus end-systole (0.90+/-0.25 vs 0.42+/-0.13, p<0.0001), in women versus men (0.85+/-0.24 vs 0.72+/-0.19, p=0.006), at anterior versus nonanterior segments (1.41+/-0.59 vs 0.88+/-0.35, p<0.0001), and at apical versus nonapical segments (1.31+/-0.56 vs 0.87+/-0.38, p<0.0001). The largest T/D ratios were associated with lower LVEF (57.0+/-5.3 vs 62+/-5.5, p=0.0001) and greater Nt-pro-BNP (203+/-98 vs 155+/-103, p=0.04). Multivariable regression identified greater end-systolic T/D ratios as the strongest independent predictor of lower LVEF, beyond age and gender, left atrial or LV volumes, and Nt-pro-BNP (beta=-9.9, 95% CI -15 to 4.9, p<0.001). In conclusion, healthy adults possess variable amounts of trabeculations that regularly meet criteria for NCC. Greater trabeculations are associated with decreased LV function. Apparently healthy young adults with increased trabecular burden possess evidence of mildly impaired cardiac function. PMID- 25132332 TI - Relation of time to coronary reperfusion and the development of acute kidney injury after ST-segment elevation myocardial infarction. AB - Time to coronary reperfusion and acute kidney injury (AKI) are powerful prognostic markers in patients with ST-segment elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI); however, no information to date is present regarding the association between time to reperfusion and AKI. We evaluated whether time to reperfusion predicts the risk of developing AKI in patients with STEMI who underwent primary PCI. Medical records of 417 patients admitted to our department from January 2008 to July 2013, for STEMI, and treated with primary PCI were reviewed. Patients were stratified by time to coronary reperfusion tertiles, and their records were assessed for the occurrence of AKI after PCI. Mean age was 61 +/- 13 years, and 346 patients (83%) were men. The cut-off points for the time to reperfusion tertiles were <120, 120 to 300, and >300 minutes. Patients having longer time to reperfusion had significantly more AKI complicating the course of STEMI (3% vs 11% vs 13%, p = 0.007) and had significantly higher serum creatinine change throughout hospitalization (0.13 vs 0.18 vs 0.21 mg/dl, p = 0.003). In a multivariable regression model, time to coronary reperfusion emerged as an independent predictor of AKI and to the maximal change in serum creatinine. In conclusion, longer time to coronary reperfusion is an independent risk factor for the development of AKI in patients with STEMI who underwent primary PCI. PMID- 25132333 TI - Transportation behaviour of fluopicolide and its control effect against Phytophthora capsici in greenhouse tomatoes after soil application. AB - BACKGROUND: Fluopicolide, a novel benzamide fungicide, was registered for control of oomycete pathogens, including Phytophthora capsici. In this study, fluopicolide (5% SC) was applied in soil at rates of 1.5, 3 and 6 L ha(-1) [the normal (ND), double (DD) and quadruple dosages (QD) respectively] to investigate its transportation behaviour and control efficiency on tomato blight as a soil treatment agent. RESULTS: The results showed that fluopicolide applied to soil could be absorbed by tomato roots and then transplanted to stems and leaves. It could exist in tomato roots for more than 30 days, and in leaves and stems until day 20 after application. The decline in fluopicolide in soil was in accordance with a first-order dynamics equation, with half-lives of 5.33, 4.75 and 5.42 days for the ND, DD and QD treatments respectively. The control efficiencies of fluopicolide were better with soil application than with spraying application, and the inhibition ratios were 93.02, 97.67 and 100 on day 21 for the ND, DD and QD treatments respectively. CONCLUSION: Soil application of fluopicolide could control P. capsici in greenhouse tomatoes with high efficiency and long persistence. PMID- 25132334 TI - Variation in amphibian response to two formulations of glyphosate-based herbicides. AB - Variation in toxicity among formulations and species makes it difficult to extrapolate results to all species and all formulations of herbicides. The authors exposed larval wood frogs (Lithobates sylvaticus) from 4 populations to 2 glyphosate-based herbicides, Roundup Weed and Grass Control(r) and Roundup WeatherMax(r). The 96-h median lethal concentration values for both formulations varied among the populations (Roundup Weed and Grass Control, 0.14 mg acid equivalents (a.e.)/L to 1.10 mg a.e./L; Roundup WeatherMax, 4.94 mg a.e./L to 8.26 mg a.e./L), demonstrating that toxicity varies among the formulations and that susceptibility may differ among populations. PMID- 25132335 TI - Protective properties of a fusion pneumococcal surface protein A (PspA) vaccine against pneumococcal challenge by five different PspA clades in mice. AB - An increase in the appearance of nonvaccine serotypes in both children and adults with invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine represents a limitation of this vaccine. In this study, we generated three recombinant pneumococcal surface protein A (PspA) proteins comprising PspA families 1 and 2, and we examined the reactivity of antisera raised in mice immunized with a PspA fusion protein in combination with CpG oligonucleotides plus aluminum hydroxide gel. The protective effects of immunization with PspA fusion proteins against pneumococcal challenge by strains with five different PspA clades were also examined in mice. Flow cytometry demonstrated that PspA3+2-induced antiserum showed the greatest binding of PspA specific IgG to all five challenge strains with different clades. PspA2+4- or PspA2+5-induced antiserum showed the lowest binding of PspA-specific IgG to clade 3. Immunization with PspA3+2 afforded significant protection against pneumococcal challenge by five strains with different clades in mice, but immunization with PspA2+4 or PspA2+5 failed to protect mice from pneumococcal challenge by strains with clades 1 and 3. The binding of PspA-specific IgG in antisera raised by three PspA fusion proteins was examined in 68 clinical isolates from adult patients with IPD. Immunization of mice with PspA3+2-induced antiserum with a high binding capacity for clinical isolates expressing clades 1-4, but not clade 5. Our results suggest that the PspA3+2 vaccine has an advantage over the PspA2+4 or PspA2+5 vaccine in terms of a broad range of cross-reactivity with clinical isolates and cross-protection against pneumococcal challenge in mice. PMID- 25132336 TI - Maternal determinants of timely vaccination coverage among infants in rural Bangladesh. AB - BACKGROUND: Timely vaccination, i.e., the receipt of all scheduled vaccinations in an age-appropriate fashion, is critical for the prevention of deadly diseases in infants and achievement of the UN Millennium Development Goal to reduce infant mortality. Infants, especially in rural or underprivileged settings often receive delayed vaccinations leaving them susceptible to vaccine-preventable illnesses early in the first year of life. In this study, we examined rates of timely vaccination among 24,435 infants born in Gaibandha and Rangpur rural districts of Bangladesh from 2001 to 2007. METHODS: Vaccinations due by 14 weeks of age and administered through routine government immunization services were assessed using interviews with enrolled mothers between 11 and 18 weeks postpartum. We created a Timely Vaccination (TV) score to classify infants as vaccinated fully and on schedule (TV=1) or not (TV=0), and used multivariable logistic regression to identify maternal characteristics associated with infant's timely vaccination status. RESULTS: Our results suggest that only 19% of infants in this cohort received scheduled vaccinations on time by 11-18 weeks postpartum. Mothers' engagement in paid employment [OR=1.13, 95% CI: 1.03-1.23], receipt of tetanus toxoid vaccination [OR=1.24, 95% CI: 1.11-1.38], history of antenatal care [OR=1.22, 95% CI: 1.12-1.32], or higher socioeconomic status [OR=1.07, 95% CI: 1.03-1.11] were positively associated with timely vaccination of their infants. Mother's perception of small infant size at birth was negatively associated with timely vaccination [OR=0.89, 95% CI: 0.82-0.97]. CONCLUSION: Timely vaccination coverage of infants in rural Gaibandha and Rangpur districts is extremely low. This analysis identifies important shortcomings associated with the 1-year vaccination benchmark of routine immunization performance and suggests the need for specific interventions based on potential maternal determinants as well as known system and programmatic barriers of timely vaccination among infants in rural Bangladesh. PMID- 25132337 TI - Uptake of influenza vaccine in ulcerative colitis. AB - BACKGROUND: The incidence of vaccine-preventable-disease is increasing. Current practice guidelines recommend annual influenza vaccination for all inflammatory bowel disease (IBD) patients. STUDY: Using the Business Objects database of Clalit Health Services in the Tel Aviv district we identified all patients over 18 years-old with a diagnosis of ulcerative colitis (UC) on 31.12.05. This cohort was followed until 31.12.12. Subjects over age 50 without IBD who are also targeted for influenza vaccination served as controls. The uptake of annual influenza vaccination was recorded. RESULTS: 470 UC patients were included (241 (51.3%) males, age 50.4 +/- 18.4 years, disease duration 158.9 +/- 86.5 months), and 2960 controls. During the years 2006, 2007, 2008, 2009, 2010, 2011 and 2012 the uptake of influenza vaccination was 101 (21.5%), 122 (26.0%), 147 (31.3%), 181 (38.5%), 177 (37.7%), 170 (36.2%) and 178 (37.9%) amongst UC patients, and 993 (33.5%), 1360 (45.9%), 1524 (51.5%), 1611 (54.4%), 1446 (48.9%), 1576 (53.2%) and 1557 (52.6%) amongst controls (p<0.0001 for every year). Independent predictors of vaccination included age (OR, 1.05; 95% CI, 1.03-1.06; p<0.001) and cardiovascular risk (OR, 1.81; 95% CI, 1.31-2.49; p<0.01). CONCLUSIONS: Although uptake influenza vaccination is consistently lower in UC compared to controls, an upward trend was observed over the study period. Public health initiatives should target this high-risk population to promote immunization. PMID- 25132338 TI - Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through PPAR-gamma activation. AB - AIM: To investigate the effects of curcumin (Cur) on cardiac fibrosis in spontaneously hypertensive rats (SHRs) and the mechanisms underlying the anti fibrotic effect of Cur in rat cardiac fibroblasts (CFs) in vitro. METHODS: SHRs were orally treated with Cur (100 mg.kg(-1).d(-1)) or Cur (100 mg.kg(-1).d(-1)) plus the PPAR-gamma antagonist GW9662 (1 mg.kg(-1).d(-1)) for 12 weeks. Cultured CFs were treated with angiotensin II (Ang II, 0.1 MUmol/L) in vitro. The expression of relevant proteins and mRNAs was analyzed using Western blotting and real-time PCR, respectively. The expression and activity of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) were detected using Western blotting and a DNA-binding assay, respectively. RESULTS: Treatment of SHRs with Cur significantly decreased systolic blood pressure, blood Ang II concentration, heart weight/body weight ratio and left ventricle weight/body weight ratio, with concurrently decreased expression of connective tissue growth factor (CTGF), plasminogen activator inhibitor (PAI)-1, collagen III (Col III) and fibronectin (FN), and increased expression and activity of PPAR-gamma in the left ventricle. Co-treatment with GW9662 partially abrogated the anti-fibrotic effects of Cur in SHRs. Pretreatment of CFs with Cur (5, 10, 20 MUmol/L) dose-dependently inhibited Ang II-induced expression of CTGF, PAI-1, Col III and FN, and increased the expression and binding activity of PPAR-gamma. Pretreatment with GW9662 partially reversed anti-fibrotic effects of Cur in vitro. Furthermore, pretreatment of CFs with Cur inhibited Ang II-induced expression of transforming growth factor-beta1 (TGF-beta1) and phosphorylation of Smad2/3, which were reversed by GW9662. CONCLUSION: Cur attenuates cardiac fibrosis in SHRs and inhibits Ang II-induced production of CTGF, PAI-1 and ECM in CFs in vitro. The crosstalk between PPAR gamma and TGF-beta1/Smad2/3 signaling is involved in the anti-fibrotic and anti proliferative effects of Cur. PMID- 25132339 TI - Crotoxin induces apoptosis and autophagy in human lung carcinoma cells in vitro via activation of the p38MAPK signaling pathway. AB - AIM: Crotoxin (CrTX) is the primary toxin in South American rattlesnake (Crotalus durissus terrificus) venom, and exhibits antitumor and other pharmacological actions in vivo and in vitro. Here, we investigated the molecular mechanisms of the antitumor action of CrTX in human lung carcinoma cells in vitro. METHODS: Human lung squamous carcinoma SK-MES-1 cells were tested. The cytotoxicity of CrTX was evaluated in both MTT and colony formation assays. Cell cycle was investigated with flow cytometry. Cell apoptosis was studied with Hoechst 33258 and Annexin V-FITC staining. The levels of relevant proteins were analyzed using Western blot assays. RESULTS: CrTX (25, 50, 100 MUmol/L) inhibited the growth and colony formation of SK-MES-1 cells in dose- and time-dependent manners. CrTX increased the proportion of S phase cells and dose-dependently induced cell apoptosis, accompanied by down-regulating the expression of proliferating cell nuclear antigen (PCNA), and increasing the level of cleaved caspase-3. Furthermore, CrTX dose-dependently increased the expression of autophagy-related proteins LC3-II and beclin 1, and decreased the level of p62 in the cells. Moreover, CrTX (50 MUmol/L) significantly increased p38MAPK phosphorylation in the cells. Pretreatment of the cells with SB203580, a specific inhibitor of p38MAPK, blocked the inhibition of CrTX on cell proliferation, as well as CrTX induced apoptosis and cleaved caspase-3 expression. CONCLUSION: The p38MAPK signaling pathway mediates CrTX-induced apoptosis and autophagy of human lung carcinoma SK-MES-1 cells in vitro. PMID- 25132341 TI - Leaf-shape remodeling: programmed cell death in fistular leaves of Allium fistulosum. AB - Some species of Allium in Liliaceae have fistular leaves. The fistular lamina of Allium fistulosum undergoes a process from solid to hollow during development. The aims were to reveal the process of fistular leaf formation involved in programmed cell death (PCD) and to compare the cytological events in the execution of cell death to those in the unusual leaf perforations or plant aerenchyma formation. In this study, light and transmission electron microscopy were used to characterize the development of fistular leaves and cytological events. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays and gel electrophoresis were used to determine nuclear DNA cleavage during the PCD. The cavity arises in the leaf blade by degradation of specialized cells, the designated pre-cavity cells, in the center of the leaves. Nuclei of cells within the pre-cavity site become TUNEL-positive, indicating that DNA cleavage is an early event. Gel electrophoresis revealed that DNA internucleosomal cleavage occurred resulting in a characteristic DNA ladder. Ultrastructural analysis of cells at the different stages showed disrupted vacuoles, misshapen nuclei with condensed chromatin, degraded cytoplasm and organelles and emergence of secondary vacuoles. The cell walls degraded last, and residue of degraded cell walls aggregated together. These results revealed that PCD plays a critical role in the development of A. fistulosum fistular leaves. The continuous cavity in A. fistulosum leaves resemble the aerenchyma in the pith of some gramineous plants to improve gas exchange. PMID- 25132340 TI - Protocol for a prospective magnetic resonance imaging study on supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity. AB - BACKGROUND: The control of the lower urinary tract is a complex, multilevel process involving both the peripheral and central nervous system. Due to lesions of the neuraxis, most spinal cord injury patients suffer from neurogenic lower urinary tract dysfunction, which may jeopardise upper urinary tract function and has a negative impact on health-related quality of life. However, the alterations to the nervous system following spinal cord injury causing neurogenic lower urinary tract dysfunction and potential effects of treatments such as intradetrusor onabotulinumtoxinA injections on lower urinary tract control are poorly understood. METHODS/DESIGN: This is a prospective structural and functional magnetic resonance imaging study investigating the supraspinal lower urinary tract control in healthy subjects and spinal cord injury patients undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Neuroimaging data will include structural magnetic resonance imaging (T1-weighted imaging and diffusion tensor imaging) as well as functional, i.e. blood oxygen level-dependent sensitive magnetic resonance imaging using a 3 T magnetic resonance scanner. The functional magnetic resonance imaging will be performed simultaneously to three different bladder stimulation paradigms using an automated magnetic resonance compatible and synchronised pump system.All subjects will undergo two consecutive and identical magnetic resonance imaging measurements. Healthy subjects will not undergo any intervention between measurements but spinal cord injury patients will receive intradetrusor onabotulinumtoxinA injections for treating neurogenic detrusor overactivity.Parameters of the clinical assessment including bladder diary, urinalysis, medical history, neuro-urological examination, urodynamic investigation as well as standardised questionnaires regarding lower urinary tract function and quality of life will serve as co-variates in the magnetic resonance imaging analysis. DISCUSSION: This study will identify structural and functional alterations in supraspinal networks of lower urinary tract control in spinal cord injury patients with neurogenic detrusor overactivity compared to healthy controls. Post-treatment magnetic resonance imaging measurements in spinal cord injury patients will provide further insights into the mechanism of action of treatments such as intradetrusor onabotulinumtoxinA injections and the effect on supraspinal lower urinary tract control. TRIAL REGISTRATION: ClinicalTrials.gov NCT01768910. PMID- 25132342 TI - Hippocampal NMDA receptors and the previous experience effect on memory. AB - N-methyl-D-aspartate receptors (NMDAR) are thought to be responsible for switching synaptic activity specific patterns into long-term changes in synaptic function and structure, which would support learning and memory. Hippocampal NMDAR blockade impairs memory consolidation in rodents, while NMDAR stimulation improves it. Adult rats that explored twice an open field (OF) before a weak though overthreshold training in inhibitory avoidance (IA), expressed IA long term memory in spite of the hippocampal administration of MK-801, which currently leads to amnesia. Those processes would involve different NMDARs. The selective blockade of hippocampal GluN2B-containing NMDAR with ifenprodil after training promoted memory in an IA task when the training was weak, suggesting that this receptor negatively modulates consolidation. In vivo, after 1h of an OF exposure with habituation to the environment-, there was an increase in GluN1 and GluN2A subunits in the rat hippocampus, without significant changes in GluN2B. Coincidentally, in vitro, in both rat hippocampal slices and neuron cultures there was an increase in GluN2A-NMDARs surface expression at 30min; an increase in GluN1 and GluN2A levels at about 1h after LTP induction was also shown. We hypothesize that those changes in NMDAR composition could be involved in the "anti-amnesic effect" of the previous OF. Along certain time interval, an increase in GluN1 and GluN2A would lead to an increase in synaptic NMDARs, facilitating synaptic plasticity and memory; while then, an increase in GluN2A/GluN2B ratio could protect the synapse and the already established plasticity, perhaps saving the specific trace. PMID- 25132343 TI - Expression of placenta growth factor, soluble fms-like tyrosine kinase-1, metal responsive transcription factor-1, heme oxygenase 1 and hypoxia inducible factor 1alpha mRNAs in pre-eclampsia placenta and the effect of pre-eclampsia sera on their expression of choriocarcinoma cells. AB - AIM: We studied the effect of pre-eclampsia sera on the expression of placenta growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), metal responsive transcription factor-1 (MTF-1), heme oxygenase 1 (HO-1) and hypoxia inducible factor-1alpha (HIF-1alpha) mRNAs in JEG-3 cells (trophoblast-derived cells) and placenta from pre-eclampsia patients to investigate pre-eclampsia pathophysiology. MATERIAL AND METHODS: Placenta and serum samples were taken from pre-eclampsia and normal pregnancy patients. JEG-3 cells were cultured with pre eclampsia and normal pregnant sera in 24-well tissue culture plates. RNA was purified from placental trophoblast cells and JEG-3 cells 24 h after incubation. The expression of mRNA was measured using real-time polymerase chain reaction. RESULTS: The expression of sFlt-1 mRNA increased, and that of PlGF and HO-1 mRNA decreased in JEG-3 cells after incubation with pre-eclampsia sera. The expression of PlGF mRNA decreased, and that of sFlt-1mRNA increased in pre-eclampsia placenta. The expression of MTF-1 and HO-1 mRNA decreased. A correlation was found between PlGF mRNA expression and the expression of MTF-1 and HIF-1alpha mRNA. A correlation between sFlt-1 and HIF-1alpha mRNA expression was also found. CONCLUSION: Changes in PlGF mRNA expression in pre-eclampsia placenta may relate to serum factors and the expression of MTF-1 and HIF-alpha mRNA. Changes in sFlt 1mRNA expression may relate to serum factors and the expression of HIF-alpha mRNA. We suggest that serum factors play a role in PlGF and sFlt-1 expression in pre-eclampsia placenta. PMID- 25132344 TI - Inflammatory features of melasma lesions in Asian skin. AB - Melasma is triggered by various factors including ultraviolet radiation and estrogen; however, its pathogenesis is unclear. To investigate the inflammatory features of melasma lesions as triggers for this disorder, 197 women with melasma who attended Asan Medical Center and Kangskin Clinic, Seoul, from June 2011 to October 2011 completed a questionnaire concerning triggering or aggravating factors. These cases were divided into "non-inflammatory" and "inflammatory" groups. Skin biopsies and immunostaining for CD68, CD117, and leukocyte common antigen (LCA) were performed in the lesional and peri-lesional skin of ten cases in the non-inflammatory group and nine cases in the inflammatory group. Among the 197 subjects (mean age, 41.5 years; mean age of melasma onset, 33.8 years), 50 patients (25.4%) were categorized into the inflammatory group. This group comprised cases that had inflammatory symptoms and events that triggered the melasma lesions. The lesional dermis contained more CD68(+) melanophages, CD117(+) mast cells, and LCA(+) leukocytes in the inflammatory group than in the non-inflammatory group. Inflammatory clinical features and an increased number of inflammatory cells in the lesion may be involved in the development of melasma in Asian skin. PMID- 25132346 TI - Pain at the game: spontaneous coronary artery dissection. PMID- 25132347 TI - Neither here nor there: impending paradoxical embolism. PMID- 25132348 TI - Ramsay Hunt syndrome presenting with ataxia and syndrome of inappropriate antidiuretic hormone secretion. PMID- 25132345 TI - Laminar and neurochemical organization of the dorsal cochlear nucleus of the human, monkey, cat, and rodents. AB - The dorsal cochlear nucleus (DCN) is a brainstem structure that receives input from the auditory nerve. Many studies in a diversity of species have shown that the DCN has a laminar organization and identifiable neuron types with predictable synaptic relations to each other. In contrast, studies on the human DCN have found a less distinct laminar organization and fewer cell types, although there has been disagreement among studies in how to characterize laminar organization and which of the cell types identified in other animals are also present in humans. We have reexamined DCN organization in the human using immunohistochemistry to analyze the expression of several proteins that have been useful in delineating the neurochemical organization of other brainstem structures in humans: nonphosphorylated neurofilament protein (NPNFP), nitric oxide synthase (nNOS), and three calcium-binding proteins. The results for humans suggest a laminar organization with only two layers, and the presence of large projection neurons that are enriched in NPNFP. We did not observe evidence in humans of the inhibitory interneurons that have been described in the cat and rodent DCN. To compare humans and other animals directly we used immunohistochemistry to examine the DCN in the macaque monkey, the cat, and three rodents. We found similarities between macaque monkey and human in the expression of NPNFP and nNOS, and unexpected differences among species in the patterns of expression of the calcium-binding proteins. PMID- 25132349 TI - Left upper pulmonary vein thrombus in a patient with atrial fibrillation and prior lobectomy. PMID- 25132350 TI - Urinary creatinine-splitting bacteria after ileal-loop diversion causing underestimate of glomerular filtration rate. PMID- 25132351 TI - What's in a word? Using words carefully. PMID- 25132352 TI - The fastest way to make an enemy. PMID- 25132353 TI - The importance and role of clinical imaging guidelines: the example of the ACR Appropriateness Criteria((r)) on Renal Failure. PMID- 25132354 TI - Osteopontin deficiency does not prevent but promotes alcoholic neutrophilic hepatitis in mice. AB - Alcoholic hepatitis (AH) is a distinct spectrum of alcoholic liver disease (ALD) with intense neutrophilic (polymorphonuclear; PMN) inflammation and high mortality. Although a recent study implicates osteopontin (SPP1) in AH, SPP1 is also shown to have protective effects on experimental ALD. To address this unsettled question, we examined the effects of SPP1 deficiency in male mice given 40% calories derived from ad libitum consumption of the Western diet high in cholesterol and saturated fat and the rest from intragastric feeding of alcohol diet without or with weekly alcohol binge. Weekly binge in this new hybrid feeding model shifts chronic ASH with macrophage inflammation and perisinusoidal and pericellular fibrosis to AH in 57% (15 of 26) of mice, accompanied by inductions of chemokines (Spp1, Cxcl1, and interleukin [Il]-17a), progenitor genes (Cd133, Cd24, Nanog, and epithelial cell adhesion molecule), PMN infiltration, and clinical features of AH, such as hypoalbuminemia, bilirubinemia, and splenomegaly. SPP1 deficiency does not reduce AH incidence and inductions of progenitor and fibrogenic genes, but rather enhances the Il-17a induction and PMN infiltration in some mice. Furthermore, in the absence of SPP1, chronic ASH mice without weekly binge begin to develop AH. CONCLUSION: These results suggest that SPP1 has a protective, rather than causal, role for experimental AH reproduced in our model. PMID- 25132356 TI - What is in a name? Nonfinancial influences on the outcomes of systematic reviews and guidelines. PMID- 25132357 TI - Judging pathological assessment in cancer specimens. AB - The pathologist plays a critical role in the multidisciplinary team in charge of treating cancer patients, as many of the therapeutic decisions rely on the information conveyed through the pathology reports. The task of the pathologist includes not only an accurate assessment of pathological T and N categories, but also the evaluation of other indicators of prognosis including quality of surgery, margins of resection, as well as additional histopathological and molecular markers that influence prognosis and could predict response to therapy. PMID- 25132355 TI - Differential cellular expression of organic anion transporting peptides OATP1A2 and OATP2B1 in the human retina and brain: implications for carrier-mediated transport of neuropeptides and neurosteriods in the CNS. AB - Organic anion transporting polypeptides (OATPs) are polyspecific organic anion transporters, which are expressed in the blood-brain barrier, the choroid plexus, and other organs. The physiologic function of OATPs in extrahepatic tissues remains ambiguous. In rat retina, members of the OATP family are expressed. We therefore investigated the human retina for the expression of OATP1A2 and OATP2B1 and extended the study to human brain. Furthermore, we searched for peptide neurotransmitters as novel OATP substrates. OATP1A2 displayed a broad expression pattern in human retina as assessed by immunofluorescence localization. It is expressed in photoreceptor bodies and somas of amacrine cells. OATP1B2 expression is restricted to the inner nuclear layer and to the inner plexiform layer. Using paraffin sections from human cortex, cerebellum, and hippocampus, OATP1A2 was localized to neurons and neuronal processes, while OATP2B1 is expressed in endothelial cells of brain capillaries. Substance P and vasoactive intestinal peptide were identified as substrates for OATP1A2 and OATP2B1. Double-labeling immunofluorescence of human retina demonstrated the presence of substance P and of vasoactive intestinal peptides in neurons expressing OATP1A2 and OATP2B1, respectively. The expression of OATP1A2 and OATP2B1 in retinal neurons implies a role of these transporters in the reuptake of peptide neurotransmitters released from retinal neurons. The abundant expression of OATP1A2 in brain neurons points to the possibility that OATP1A2 could be involved in the homeostasis of neurosteroids. The high expression of OATP2B1 in brain capillaries supports an important function of OATPs in substance penetration across the blood-brain barrier. PMID- 25132358 TI - phylin: an r package for phylogeographic interpolation. AB - phylin is a package for the r programming environment which offers different methods to spatially interpolate genetic information from phylogeographic data. These interpolations can be used to predict the spatial occurrence of different lineages within a phylogeny using a modified method of kriging, which allows the usage of a genetic distance matrix to derive a model of spatial dependence. phylin improves the available methods to generate interpolated surfaces from a phylogenetic trees by assessing the autocorrelation structure of the genetic information, interpolating the genetic data based on a statistical model, estimating the uncertainty of the predictions and identifying lineage occurrence and contact zones probability without projection of pairwise genetic distances into mid-points between sample locations. The package also includes methods to plot interpolation surfaces and provide summary tables from the generated data and models. We provide an example of the usefulness of this tool by inferring the spatial occurrence of distinct historical evolutionary lineages of the Lataste's viper (Vipera latastei Bosca, 1878) in the Iberian Peninsula and identifying potential contact areas. The maps of phylogenetic patterns obtained with these methods provide a spatial context to test hypotheses related to processes underlying the geographic distribution of genetic diversity and to inform conservation planning. PMID- 25132359 TI - Cancer research in France. PMID- 25132360 TI - Exercise decreases speedball self-administration. AB - AIMS: Epidemiological studies report that individuals who exercise are less likely to abuse drugs. Preclinical studies report that exercise, in the form of treadmill or wheel running, reliably decreases the self-administration of psychomotor stimulants and opioids. To date, preclinical studies have only examined the effects of exercise on responding maintained by individual drugs and not by combinations of multiple drugs. This limits the translational appeal of these studies because polydrug abuse is common among substance abusing populations. The purpose of this study was to examine the effects of exercise on the self-administration of speedball, a combination of cocaine and heroin that is frequently encountered in intravenous drug abusing populations. MAIN METHODS: Female rats were obtained at weaning and assigned to sedentary or exercising conditions. Sedentary rats were housed in standard cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed in similar cages with an activity wheel. After 6weeks, rats were implanted with intravenous catheters and trained to self-administer cocaine, heroin, and dose combinations of cocaine and heroin (i.e., speedball) on a progressive ratio schedule of reinforcement. KEY FINDINGS: Doses of speedball maintained greater levels of responding than corresponding doses of cocaine and heroin alone. Importantly, responding maintained by cocaine, heroin, and speedball was lower in exercising rats than sedentary rats. SIGNIFICANCE: These data indicate that exercise decreases the self-administration of speedball and suggest that exercise may reduce the abuse of drug combinations that have traditionally been resistant to treatment. PMID- 25132361 TI - Gastrodin prevents motor deficits and oxidative stress in the MPTP mouse model of Parkinson's disease: involvement of ERK1/2-Nrf2 signaling pathway. AB - AIMS: Current no effective therapy is available to halt the progression of Parkinson's disease (PD). Oxidative stress has been implicated in the etiology of PD. The present study evaluates the hypothesis that prevention of 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor deficits by gastrodin might mainly result from its antioxidant property via interrupting extracellular signal regulated protein kinases (ERK) 1/2-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MAIN METHODS: Pretreatment of mouse model of PD is established by treating C57BL/6 mice with 4 doses of MPTP (30 mg/kg per day, i.p.), with gastrodin (60 mg/kg per day) administered by daily intraperitoneal injection for 2 weeks. Motor behavior of mice was monitored by open-field test and rotarod test. Real-time polymerase chain reaction and Western blotting were used to analyze the expression of genes. KEY FINDINGS: MPTP-induced motor deficits were partially and significantly forestalled by gastrodin. Gastrodin treatment prevented MPTP-induced oxidative stress, as measured by malondialdehyde in midbrain. Interestingly, MPTP-intoxicated mice treated with gastrodin robustly increased heme oxygenase 1, superoxide dismutase, glutathione levels, and Nrf2 nuclear translocation in striatum of MPTP-intoxicated mice. Furthermore, results herein suggest that the antioxidant pathway activated by gastrodin involves ERK1/2 phosphorylation. SIGNIFICANCE: Gastrodin protects midbrain of MPTP-intoxicated mice against oxidative stress, in part, through interrupting ERK1/2-Nrf2 pathway mechanism, which will give us an insight into the potential of gastrodin in terms of opening up new therapeutic avenues for PD. PMID- 25132362 TI - Animal models of social anxiety disorder and their validity criteria. AB - Anxiety disorders pose one of the largest threats to global mental health, and they predominantly emerge early in life. Social anxiety disorder, also known as social phobia, is the most common of all anxiety disorders. Moreover, it has severe consequences and is a disabling disorder that can cause an individual to be unable to perform the tasks of daily life. Social anxiety disorder is associated with the subsequent development of major depression and other mental diseases, as well as increased substance abuse. Although some neurobiological alterations have been found to be associated with social anxiety disorder, little is known about this disorder. Animal models are useful tools for the investigation of this disorder, as well as for finding new pharmacological targets for treatment. Thus, this review will highlight the main animal models of anxiety associated with social phobia. PMID- 25132363 TI - The flavan-3-ol fraction of cocoa powder suppressed changes associated with early stage metabolic syndrome in high-fat diet-fed rats. AB - AIMS: Previous epidemiological studies have suggested that ingestion of chocolate reduces the risk of cardiovascular disease. In the present study, we examined the effects of flavan-3-ols derived from cocoa on blood pressure, lipolysis, and thermogenesis in rats fed a high-fat diet and that showed early signs of metabolic syndrome. MAIN METHODS: The rats were divided into three groups, and fed either normal diet (normal), 60% fat high-fat diet (HFD), or HFD containing 0.2% flavan-3-ols (HFD-flavan) for 4 weeks. At the end of the feeding period, blood pressure was measured and animals were sacrificed under anesthesia. Lipolysis and thermogenesis-related protein levels were measured in several tissues by Western blotting, and mitochondrial DNA copy number was measured by RT PCR. KEY FINDINGS: Mean blood pressure and epididymal adipose tissue weight of HFD-flavan were significantly lower compared with those of HFD. Uncoupling protein (UCP)1 in brown adipose tissue and UCP3 in gastrocnemius of HFD-flavan were significantly increased compared with those of HFD group. Carnitine palmitoyltransferase (CPT) 2 levels in liver and medium-chain acyl-CoA dehydrogenase (MCAD) levels in gastrocnemius and liver were significantly increased by the supplementation of flavan-3-ols. SIGNIFICANCE: In addition to having hypotensive effects, flavan-3-ols enhance thermogenesis and lipolysis and consequently reduce white adipose tissue weight gain in response to high-fat diet feeding. PMID- 25132364 TI - In-office bleaching gel with 35% hydrogen peroxide enhanced biofilm formation of early colonizing streptococci on human enamel. AB - OBJECTIVES: To compare the effects of 25% and 35% hydrogen peroxide in-office bleaching systems on surface roughness and streptococcal biofilm formation on human enamel. METHODS: Enamel specimens (3mm*3mm*2mm, n=162) from human permanent teeth were randomly divided into 3 treatment groups (n=54 each): (1) control, (2) bleached with 25% hydrogen peroxide (Zoom2TM), and (3) bleached with 35% hydrogen peroxide (BeyondTM). The enamel surface roughness was measured by a profilometer before and after treatments. Subsequently, the treated enamel specimens were randomly placed into 3 subgroups (n=18 each) and incubated with: (1) trypticase soy broth control, (2) Streptococcus mutans culture and (3) Streptococcus sanguinis culture for 24h. Biofilm formation was quantified by crystal violet staining. The biofilm structure on three specimens from each group was visualized by scanning electron microscopy. Data were analyzed by Kruskal-Wallis and Mann Whitney U tests with Bonferroni corrections. Significance level was set at p<0.05. RESULTS: Both bleaching systems significantly reduced enamel surface roughness comparing to the control group (p<0.001), but there was no difference between the two treatment groups. Remarkably, S. sanguinis biofilm formation was significantly higher on enamel specimens bleached with 35% hydrogen peroxide than other treatments (p<0.001), but was lower on those bleached with 25% hydrogen peroxide (p<0.001). In contrast, no difference in S. mutans biofilm formation was observed among the three treatment groups. CONCLUSION: Both 25% and 35% hydrogen peroxide caused similar degrees of reduction in enamel surface roughness. Nevertheless, bleaching with 35% hydrogen peroxide appeared to markedly promote S. sanguinis biofilm formation. CLINICAL SIGNIFICANCE: The increase of early colonizer biofilm raised concerns over adverse effects of in-office bleaching on plaque formation. This should be further investigated in vivo and efficient plaque control should be emphasized after bleaching with high concentrations of hydrogen peroxide. PMID- 25132365 TI - The strength of sintered and adhesively bonded zirconia/veneer-ceramic bilayers. AB - OBJECTIVES: Recently all-ceramic restorative systems have been introduced that use CAD/CAM technology to fabricate both the Y-TZP core and veneer-ceramic layers. The aim was to identify whether the CAD/CAM approach resulted in more favourable stressing patterns in the veneer-ceramic when compared with a conventionally sintered Y-TZP core/veneer-ceramic. METHODS: Nominally identical Vita VM9 veneer-ceramic disc-shaped specimens (0.7mm thickness, 12mm diameter) were fabricated. 20 specimens received a surface coating of resin-cement (Panavia 21); 20 specimens were bonded with the resin-cement to fully sintered Y-TZP (YZ Vita Inceram Vita) discs (0.27mm thickness, 12mm diameter). A final series of 20 Y-TZP core/veneer-ceramic specimens were manufactured using a conventional sintering route. Biaxial flexure strength was determined in a ball-on-ring configuration and stress at the fracture origin calculated using multilayer closed-form analytical solutions. Fractography was undertaken using scanning electron microscopy. The experimental test was simulated using Finite Element Analysis. Group mean BFS were compared using a one-way ANOVA and post hoc Tukey tests at a 95% significance level. RESULTS: Resin cement application resulted in significant strengthening of the veneer-ceramic and further significant strengthening of the veneer-ceramic (p<0.01) occurred following bonding to the Y TZP core. The BFS calculated at the failure origin for conventionally sintered specimens was significantly reduced when compared with the adhesively bonded Y TZP/veneer-ceramic. CONCLUSIONS: Under the test conditions employed adhesive cementation between CAD/CAM produced Y-TZP/veneer-ceramic layers appears to offer the potential to induce more favourable stress states within the veneer-ceramic when compared with conventional sintered manufacturing routes. CLINICAL SIGNIFICANCE: The current investigation suggests that the stressing patterns that arise in all-ceramic restorations fabricated using CAD/CAM for both the core and veneer-ceramic layers differ from those that occur in conventionally sintered bilayer restorations. Further work is required to ascertain whether such differences will translate into improved clinical outcomes. PMID- 25132366 TI - Effect of temperature on post-cure polymerization of bulk-fill composites. AB - OBJECTIVES: To investigate the 24h post-cure polymerization and the effect of temperature on the post-cure polymerization of one conventional and three bulk fill composite materials. METHODS: A conventional composite GrandioSO (GR) and three bulk-fill composites: Tetric EvoCeram Bulk Fill (TECBF), Quixfil (QF) and X tra fil (XF) were investigated. The samples were cured for 20s with irradiance of 1090mW/cm(2). Composite samples were divided into two groups: the "room temperature" group (RT, n=5) and the "body-temperature" group (BT, n=5) and they were stored in dark at 20 degrees C and 37 degrees C, respectively. Measurements of degree of conversion (DC) were made immediately after curing (0h) and 24h post cure (24h). To analyse the extent of post-cure DC increase, the DC values of 0h RT/24h-RT and 0h-BT/24h-BT were compared. To analyse the difference in DC between RT and BT, the DC values of 0h-RT/0h-BT and 24h-RT/24h-BT were compared. RESULTS: DC increase 24h post-cure was significant for all composites and ranged between 6.3% and 8.2% in RT and between 12.5% and 15.7% in BT. All composites demonstrated a higher DC in 24h-BT compared to 24h-RT. The difference was statistically significant for GR, TECBF and QF. CONCLUSIONS: All composites demonstrated a significant post-cure effect after 24h. Post-cure temperature increase from 20 degrees C to 37 degrees C yielded a higher post-cure DC increase. CLINICAL SIGNIFICANCE: Due to the temperature effect on the final DC, studies performed at composite samples at room temperature may record more inferior properties than these attained in the oral cavity. PMID- 25132368 TI - Salivary gland carcinomas in children and adolescents: the Italian TREP project experience. AB - BACKGROUND: Salivary gland carcinomas are extremely rare in pediatric age. We report the clinical features of a series of children/adolescents with salivary gland carcinomas prospectively registered in the Italian TREP (Rare Tumors in Pediatric Age) project. PROCEDURES: Diagnostic/therapeutic guidelines were developed and shared among Italian pediatric oncology/surgical centers. RESULTS: Seventeen patients were registered between 2000 and 2012, representing 19% of the cases expected to be seen based on epidemiological data. Tumors arose mainly in the parotid gland (14 cases). In most cases they were low-grade tumors (14 cases), often with a favorable clinical presentation, and low-stage disease. All patients underwent surgical resection, achieving histologically free margins in 9/17 cases. Thirteen of the 14 patients with parotid gland tumors had parotidectomy (10 total, 3 superficial), while one had a tumorectomy. Postoperative facial nerve lesions were reported in two cases. Adjuvant radiotherapy was given to 6 patients. The overall prognosis was good: only one patient with a huge high-grade tumor experienced disease progression and died of the disease. The other 16 patients were alive in first continuous remission 1-8 years after diagnosis. In 4/17 cases, the salivary gland carcinoma was a second tumor occurring 6-9 years after another primary cancer. CONCLUSIONS: This is the first reported prospective national cooperative series of pediatric salivary gland carcinoma patients. Compliance with the TREP recommendations was high. These tumors are rarely managed by pediatric oncologists/surgeons. A broader international cooperation and better networking with otolaryngologists and head neck surgeons expert on adult salivary gland carcinomas would be advisable. PMID- 25132367 TI - Marginal integrity and secondary caries of selectively excavated teeth in vitro. AB - OBJECTIVES: Selective caries removal involves sealing of carious dentine beneath restorations, which might decrease their marginal integrity and increase the susceptibility for secondary caries and microleakage. The present study compared these marginal characteristics of restorations in selectively and completely excavated teeth. METHODS: In 32 premolars, shallow and deep artificial lesions were created on pulpo-axial walls of mesial-distal-occlusal cavities, with mesial and distal margins located in enamel and dentine, respectively. Demineralised dentine was either removed or left before adhesively restoring the teeth (n=8), which were then submitted to thermo-mechanical cycling. The integrity of gingivo cervical margins was assessed using scanning electron microscopy. In half of each margin, caries was induced adjacent to restorations using a continuous-culture biofilm model, and resulting lesions were evaluated using transversal microradiography. The other half of each margin was used to assess microleakage. RESULTS: Integrity or microleakage of margins located in enamel did not differ significantly between groups, and bacterial biofilms did not induce distinct caries lesions in enamel. Dentinal margins in teeth with deep compared with shallow lesions showed a significantly higher proportion of marginal imperfections, gaps and microleakage (p<=0.05, Mann-Whitney/chi(2)-test). In contrast, neither marginal integrity nor microleakage differed significantly between completely and selectively excavated teeth (p>0.05). Dentinal mineral loss adjacent to restorations did not differ significantly between groups (p>0.80). CONCLUSIONS: The marginal characteristics of restorations were affected by the depth of sealed or excavated lesions, but not by the performed caries excavation. This study did not find selective excavation detrimental for restoration integrity in vitro. CLINICAL SIGNIFICANCE: Selective excavation of deep lesions was shown to reduce pulpal risks, whilst leaving caries beneath restorations is feared to compromise the marginal characteristics of the subsequently placed restoration. Based on the present in vitro study, such assumptions cannot be supported. PMID- 25132369 TI - Proton and deuterium nuclear spin relaxation study of the SmA and SmC* phases of BP8Cl-d17 : a self-consistent analysis. AB - A self-consistent analysis of proton and deuterium nuclear spin relaxation times in the smectic phases of a partially deuterated smectogen is presented here. Proton spin-lattice relaxation times T(1Z) were measured as a function of Larmor frequency over a range of 1 kHz to 300 MHz at selected temperatures. Deuterium spin relaxation times T(1Z) and T(1Q) were measured as a function of temperature at two different magnetic fields in the smectic A phase. The deuterium data provide dynamic parameters such as rotational diffusion constants and internal jump rates as well as the nematic order parameter S. The proton data are analyzed using a number of relaxation mechanisms, one of which is the molecular reorientation. It is found helpful in these latter analyses to use the nematic order parameter and to fix the contribution from molecular reorientations determined by the deuterium spin relaxation. The fits to the proton T(1) frequency and temperature dispersions by the remaining relaxation mechanisms such as layer undulations and translational self-diffusion will be discussed for the smectic A and chiral smectic C phases. PMID- 25132370 TI - Clinical phenotype and genetic analysis of RPS19, RPL5, and RPL11 genes in Greek patients with Diamond Blackfan Anemia. AB - BACKGROUND: Diamond Blackfan Anemia (DBA) is a rare congenital, bone marrow failure syndrome characterized by normochromic macrocytic anemia, reticulocytopenia and absence or insufficiency of erythroid precursors in normocellular bone marrow, frequently associated with somatic malformations. Here, we present our findings from the study of 17 patients recorded in the Greek DBA registry. PROCEDURE: Clinical evaluation of patients and data collection was performed followed by the molecular analysis of RPS19, RPL5, and RPL11 genes. Mutation screening included PCR amplification, ECMA analysis, and direct sequencing. RESULTS: Congenital anomalies were observed in 71% of the patients. Six patients (35.2%) were found to carry mutations on either the RPS19 gene (three patients,) or the RPL5 gene (three patients). Mutations c.C390G (p.Y130X) and c.197_198insA (p.Y66X) detected in the RPL5 gene were novel. No mutations at the RPL11 gene were identified in Greek patients with DBA. CONCLUSIONS: The clinical course of the patients was similar to previous reports. The occurrence of thyroid carcinoma in an adult patient with DBA is the first to be reported in DBA. PMID- 25132371 TI - Non-disclosure of widowhood in Nepal: implications for women and their children. AB - Non-disclosure of significant or emotionally charged information can have psychological and physical health consequences. Widowhood in Nepal is highly stigmatised and therefore is a sensitive topic. This study sought to understand why and to whom women do not disclose their status as widows. Thematic content analysis of 31 in-depth interviews and 6 focus groups was conducted with primarily high-caste widows of reproductive age from the Kathmandu Valley, Surkhet, Chitwan and Kavre districts of Nepal. A codebook was developed based upon recurring concepts and applied to all transcripts using Atlas.ti. Due to discomfort or stigmatisation, many women concealed their status as widows in the community through behaviours impacting their daily lives. Non-disclosure to children was frequently described, often as a way to protect them from psychological sequelae. Concealment of widowhood is a coping strategy Nepali women use to shield themselves against societal stigma and to manage bereavement in their children. Efforts are needed to support widows in dealing with mental health issues related to disclosure and the psychosocial impact on their children. PMID- 25132372 TI - Exposure to rufinamide and risks of CNS adverse events in drug-resistant epilepsy: a meta-analysis of randomized, placebo-controlled trials. AB - AIM: Epilepsy is a complex disease necessitating continuous development of new therapeutic strategies to encounter drug-resistant cases. Among new adjuvant antiepileptic drugs, rufinamide is structurally distinct from other antiepileptic drugs. It is used to treat partial-onset seizures and seizures associated with Lennox-Gastaut syndrome (LGS) in adult and children. To date, there has been no attempt to evaluate systematically the risks of adverse events with rufinamide. METHODS: We performed a quantitative risk analysis of central nervous system (CNS) adverse events of rufinamide from all randomized, double-blind, add-on, placebo-controlled trials. The meta-analysis was undertaken with fixed effects models. RESULTS: Of the 886 publications reviewed, 99 papers were retrieved and five articles met the inclusion criteria. One thousand two hundred and fifty-two patients were included. Our study showed that exposure to rufinamide was associated with a significant increase in risk of somnolence [relative ratio (RR) 1.87; 95% confidence interval (CI) 1.33, 2.62; P = 0.0003], dizziness (RR 2.66; 95% CI 2.00, 3.55; P = 0.00001), fatigue (RR 2.14; 95% CI 1.57, 2.91; P = 0.01) and headache (RR 1.28; 95% CI 1.02, 1.59, P = 0.03). In addition, exposure to rufinamide was associated with higher treatment discontinuation rates as compared with placebo (RR 2.65; 95% CI 1.74, 4.03; P = 0.00001). CONCLUSIONS: The risk of CNS adverse events appears to be increased in patients exposed to rufinamide as well as the treatment discontinuation rates. However, although statistical associations were significant, additional long term safety studies are required to confirm the clinical significance of these findings, as most reports described only mild and moderate adverse events. PMID- 25132373 TI - Human papillomavirus type-specific prevalence in women referred for colposcopic examination in Beijing. AB - Human papillomavirus (HPV) is associated with several disorders of the genital tract, skin, and oropharynx. This study investigated the prevalence of infection by 37 HPV genotypes among women of the Beijing area in China. Cervical specimens from 1,082 patients and 165 healthy controls were tested for HPV genotypes using a chip hybridization assay. Based on the local pathology, patients were divided into cervicitis and cervical lesion groups. Overall HPV infection rates were 30.5% for the cervicitis group and 78.4% for the cervical lesion group; whereas infection rates for high-risk HPV types (i.e., those associated with cervical cancers) were 24.0% and 73.4%, respectively. The most common HPV genotypes were HPV 52, 16, 81, 58, and 18 in healthy controls, HPV 52, 61, 55, 16, and 53 in those with cervicitis, HPV 52, 16, 33, 39, and 58 in cervical intraepithelial neoplasia grade 1, HPV 16, 58, 31, 52, and 33 in cervical intraepithelial neoplasia grade 2 or grade 3, and HPV 16, 33, 18, 52, and 58 in cervical cancer. Established high-risk HPV showed two peaks, in patients aged 30-34 and 55-79 years. In Beijing, HPV 16, 52, 58, and 33 are the most prevalent HPV types in women with cervical lesions, which should affect development of a cervical cancer vaccination for local use. PMID- 25132374 TI - Identification and characterization of microRNAs in oilseed rape (Brassica napus) responsive to infection with the pathogenic fungus Verticillium longisporum using Brassica AA (Brassica rapa) and CC (Brassica oleracea) as reference genomes. AB - Verticillium longisporum, a soil-borne pathogenic fungus, causes vascular disease in oilseed rape (Brassica napus). We proposed that plant microRNAs (miRNAs) are involved in the plant-V. longisporum interaction. To identify oilseed rape miRNAs, we deep-sequenced two small RNA libraries made from V. longisporum infected/noninfected roots and employed Brassica rapa and Brassica oleracea genomes as references for miRNA prediction and characterization. We identified 893 B. napus miRNAs representing 360 conserved and 533 novel miRNAs, and mapped 429 and 464 miRNAs to the AA and CC genomes, respectively. Microsynteny analysis with the conserved miRNAs and their flanking protein coding sequences revealed 137 AA-CC genome syntenic miRNA pairs and 61 AA and 42 CC genome-unique miRNAs. Sixty-two miRNAs were responsive to the V. longisporum infection. We present data for specific interactions and simultaneously reciprocal changes in the expression levels of the miRNAs and their targets in the infected roots. We demonstrate that miRNAs are involved in the plant-fungus interaction and that miRNA168-Argonaute 1 (AGO1) expression modulation might act as a key regulatory module in a compatible plant-V. longisporum interaction. Our results suggest that V. longisporum may have evolved a virulence mechanism by interference with plant miRNAs to reprogram plant gene expression and achieve infection. PMID- 25132375 TI - Type V collagen counteracts osteo-differentiation of human mesenchymal stem cells. AB - In search of novel gene signatures for osteo-differentiation of mesenchymal stem cells (MSCs), we submitted cDNA preparations from undifferentiated and differentiating MSCs to differential display- and semiquantitative-PCR and found down-regulation of COL5A1 in osteo-induced cultures at days 21 and 28, when the mineralized matrix accumulates. We also cultured osteo-differentiating MSCs onto type V collagen substrates and found a decrease in the accumulation of extracellular calcium compared to those grown in uncoated flasks. To our knowledge, this is first evidence that type V collagen might represent a stromal component that impairs osteogenesis. PMID- 25132376 TI - Percutaneous carbon dioxide treatment using a gas mist generator enhances the collateral blood flow in the ischemic hindlimb. AB - AIM: Highly concentrated carbon dioxide (CO2) is thought to be useful for ischemic diseases. We investigated whether treatment with a few micrometers of CO2 molecules atomized via two fluidnozzles (CO2 mist) exerts an angiogenic effect in a mouse ischemic hindlimb model. METHODS: Mice with unilateral hindlimb ischemia were divided into untreated (UT), 100% CO2 gas alone-treated (CG), mixed air (O2; 20%, N2; 80%) mist-treated (AM) and 100% CO2 mist-treated (CM) groups. The lower body of the mice was encased in a polyethylene bag filled with each gaseous agent using a gas mist generator for 10 minutes daily. RESULTS: According to a laser Doppler analysis, the ischemic hindlimb blood flow was persistently higher after the seventh day of induction of ischemia in the CM group than in the UT group. The capillary density was also greater in the CM group on day 28 compared with that observed in the UT group. In addition, the parameters in the AM and CG groups were similar to those obtained in the UT group. The observed effects were abolished by the administration of an inhibitor of nitric oxide synthase (NOS). The vascular endothelial growth factor mRNA expression and protein levels and the phosphorylated endothelial NOS level were increased in the CM group compared with that observed in the UT group. A proteomic analysis using liquid chromatography-tandem mass spectrometry identified novel protein candidates regulated by CO2 mist. CONCLUSION: Percutaneous CO2 mist therapy may be useful for treating ischemia-induced angiogenesis. PMID- 25132377 TI - The expression of groups IIE and V phospholipase A2 is associated with an increased expression of osteogenic molecules in human calcified aortic valves. AB - AIM: Eicosanoids play various pathogenic roles in aortic valve calcification. Eicosanoids are derived from the arachidonic acid generated by phospholipase A2 (PLA2). We therefore sought to determine whether PLA2s are expressed in human aortic valves and, if so, whether the expression of PLA2s is related to the expression of osteogenic molecules in these tissues. METHODS: Histological and gene expression analyses of 38 non-rheumatic aortic valves obtained at the time of cardiac valve replacement surgery were conducted. Moreover, gene expression analyses were performed using valve interstitial cells (VICs) obtained from human aortic valves. RESULTS: Among the PLA2s examined, the degree of immunoreactivity for PLA2s-IIE and -V was found to significantly correlate with the grade of calcification in the aortic valves. The degree of immunoreactivity and gene expression levels of PLA2s-IIE and -V significantly correlated with those of bone morphogenetic protein (BMP)-2, osteopontin and alkaline phosphatase (ALP). In addition, immunoreactivity for cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase, downstream enzymes of PLA2 in the arachidonic acid cascade, was co-localized with that for PLA2s-IIE and -V in cells expressing alpha-smooth muscle actin and macrophages expressing CD68. Furthermore, in the in vitro experiments using cultured VICs, the mRNA expression levels of BMP-2, osteopontin and ALP were suppressed by the inhibition of the expression of PLA2s-IIE or -V with specific siRNAs. CONCLUSIONS: The expression of PLA2s-IIE and -V correlates with the development of calcification as well as the expression of pro-osteogenic molecules in human aortic valves, and inhibiting the expression of PLA2s-IIE and V suppresses the induction of osteogenic molecules in cultured cells. Therefore, PLA2s-IIE and -V may play a role in the pathogenesis of valve calcification. PMID- 25132378 TI - Antioxidant effects of statins in the management of cardiometabolic disorders. AB - Redox systems are key players in vascular health. A shift in redox homeostasis that results in an imbalance between reactive oxygen species (ROS) generation and endogenous antioxidant defenses has the potential to create a state of oxidative stress that subsequently plays a role in the pathogenesis of a number of diseases, including those of the cardiovascular and metabolic system. Statins, which are primarily used to reduce the concentration of low-density lipoprotein cholesterol, have also been shown to reduce oxidative stress by modulating redox systems. Studies conducted both in vitro and in vivo support the role of oxidative stress in the development of atherosclerosis and cardiovascular diseases. Oxidative stress may also be responsible for various diabetic complications and the development of fatty liver. Statins reduce oxidative stress by blocking the generation of ROS and reducing the NAD+/NADH ratio. These drugs also have effects on nitric oxide synthase, lipid peroxidation and the adiponectin levels. It is possible that the antioxidant properties of statins contribute to their protective cardiovascular effects, independent of the lipid lowering actions of these agents. However, possible adverse effects of statins on glucose homeostasis may be related to the redox system. Therefore, studies investigating the modulation of redox signaling by statins are warranted. PMID- 25132380 TI - Closed suction drainage for treatment of septic peritonitis of confirmed gastrointestinal origin in 20 dogs. AB - OBJECTIVE: To determine survival rate in dogs with septic peritonitis of confirmed gastrointestinal origin treated with closed suction drainage. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 20) with septic peritonitis. METHODS: Medical records (2007-2010) of dogs with septic peritonitis of confirmed gastrointestinal origin treated by closed suction drainage were reviewed. Information on signalment, clinicopathologic abnormalities, underlying cause, surgical procedure performed, postoperative management, complications, and outcome was obtained. RESULTS: Dehiscence of a previous anastomosis was the most common source of contamination (80%). Drains remained in place, collecting fluid produced within the abdomen, for a median of 6 days (range, 2-11 days). Eighteen dogs received nutritional support, and 14 received plasma transfusions. Seventeen dogs (85%) survived to discharge. CONCLUSIONS: Closed suction drainage together with resolution of the underlying cause of peritonitis and appropriate postoperative management is an effective technique for treatment of septic peritonitis of confirmed gastrointestinal origin in dogs. PMID- 25132379 TI - Impact of eicosapentaenoic acid treatment on the fibrous cap thickness in patients with coronary atherosclerotic plaque: an optical coherence tomography study. AB - AIM: Previous clinical trials have demonstrated the effectiveness of eicosapentaenoic acid (EPA) in preventing cardiovascular events. The aim of the present study was to investigate the effects of EPA treatment on the accumulation of coronary atherosclerotic plaque using optical coherence tomography (OCT). METHODS: A total of 46 acute coronary syndrome (ACS) patients without dyslipidemia were divided into two groups: those who received 1,800 mg/day of EPA (n = 15) or the control group (n = 31). Serial OCT examinations were performed at baseline and after eight months of follow-up. The target for the OCT analysis was non-culprit plaque with a percent diameter of stenosis of 30% to 70% in non culprit vessels of ACS. RESULTS: Between the baseline and follow-up visits, the serum EPA levels increased (50 +/- 26 mg/dL to 200 +/- 41 mg/dL, p < 0.001) in the EPA group, although they did not change in the control group. According to the OCT analysis, the lipid arc did not change in the EPA group (131 +/- 52 degrees to 126 +/- 54 degrees, p = 0.106) or the control group (137 +/- 50 degrees to 138 +/- 50 degrees, p=0.603). In contrast, the fibrous cap thickness significantly increased in both the EPA group (169 +/- 70 MUm to 201 +/- 49 MUm, p < 0.001) and the control group (164 +/- 63 MUm to 174 +/- 72 MUm, p=0.018); however, the relative change in the fibrous cap thickness was significantly greater in the EPA group than in the control group (131 +/- 35% vs. 106 +/- 15%, p = 0.001). CONCLUSIONS: In the present study, the administration of EPA for eight months significantly increased the fibrous cap thickness in patients with coronary atherosclerotic plaque. PMID- 25132381 TI - Photoluminescent nematic liquid crystalline elastomer with a thermomechanical emission variation function. AB - Nematic liquid crystalline elastomer (LCE) microactuators are developed, showing simultaneous thermomechanical deformation and photoluminescence (PL) emission variation functions. The microactuators are prepared by a method combining soft lithography and photo-polymerization/crosslinking. 1,4-Bis(alpha-cyano-4 methoxystyryl)benzene as the PL dye is synthesized, characterized, and introduced into LCEs as a dopant in the preparation process. During the heating process, PL emission of the LCE micropillars under blue light excitation becomes significantly weak when the micropillars contract. When cooling down, the emission completely recovers as the micropillars stretches back to their original shape. The PL intensity variation at the transition is proved to be related to the thermomechanical deformation. PMID- 25132383 TI - How hard is hard enough? An investigation of the force associated with lateral blunt force trauma to the porcine cranium. AB - Blunt force trauma forms a substantial portion of deaths worldwide. However, few studies have attempted to determine the force involved with blunt force trauma to the lateral part of the head. Nor have many studies been conducted at velocities exceeding 10 m/s. The acquisition of human tissue for experimental studies is becoming increasingly difficult. As such, the current study investigates the trauma and the force involved with cranial blunt force trauma in a porcine model. Thirty whole porcine heads were subjected to single impact tests on the fronto parietal region at velocities ranging from 10 m/s to 25 m/s. Half the specimens were subjected to impact by a short projectile resembling a hammer head and the other half were subjected to impact with a Hopkinson pressure bar (HPB). Both implements had the same impact diameter and were machined from the same material. The HPB is an apparatus commonly used in material testing. Its use to determine fracture force in whole cranial specimens is novel. Fractures appeared similar in both the hammer tests and HPB tests. Lacerations and fractures resembled the shape of the striker surface with the most common fracture observed being a semi circular depressed fracture. The mean peak fracture force was 7760 N (+/- 4150 N), with a mean displacement of 3.1mm (+/- 1.1mm). Peak fracture forces concur well with previous studies although no clear trend appears to exist between level of trauma and peak impact force. PMID- 25132382 TI - Neutralizing antibodies inhibit HIV-1 infection of plasmacytoid dendritic cells by an FcgammaRIIa independent mechanism and do not diminish cytokines production. AB - Plasmacytoid dendritic cells (pDC) expressing FcgammaRIIa are antigen-presenting cells able to link innate and adaptive immunity and producing various cytokines and chemokines. Although highly restricted, they are able to replicate HIV-1. We determined the activity of anti-HIV-1 neutralizing antibodies (NAb) and non neutralizing inhibitory antibodies (NNIAb) on the infection of primary pDC by HIV 1 primary isolates and analyzed cytokines and chemokines production. Neutralization assay was performed with primary pDC in the presence of serial antibodies (Ab) concentrations. In parallel, we measured the release of cytokines and chemokines by ELISA and CBA Flex assay. We found that NAb, but not NNIAb, inhibit HIV-1 replication in pDC. This inhibitory activity was lower than that detected for myeloid dendritic cells (mDC) infection and independent of FcgammaRIIa expressed on pDC. Despite the complete protection, IFN-alpha production was detected in the supernatant of pDC treated with NAb VRC01, 4E10, PGT121, 10-1074, 10E8, or polyclonal IgG44 but not with NAb b12. Production of MIP-1alpha, MIP-1beta, IL-6, and TNF-alpha by pDC was also maintained in the presence of 4E10, b12 and VRC01. These findings suggest that pDC can be protected from HIV-1 infection by both NAb and IFN-alpha release triggered by the innate immune response during infection. PMID- 25132384 TI - A self-organizing miR-132/Ctbp2 circuit regulates bimodal notch signals and glial progenitor fate choice during spinal cord maturation. AB - Radial glial progenitors play pivotal roles in the development and patterning of the spinal cord, and their fate is controlled by Notch signaling. How Notch is shaped to regulate their crucial transition from expansion toward differentiation remains, however, unknown. miR-132 in the developing zebrafish dampens Notch signaling via a cascade involving the transcriptional corepressor Ctbp2 and the Notch suppressor Sirt1. At early embryonic stages, high Ctbp2 levels sustain Notch signaling and radial glial expansion and concomitantly induce miR-132 expression via a double-negative feedback loop involving Rest inhibition. The changing balance in miR-132 and Ctbp2 interaction gradually drives the switch in Notch output and radial glial progenitor fate as part of the larger developmental program involved in the transition from embryonic to larval spinal cord. PMID- 25132385 TI - A MYB-domain protein EFM mediates flowering responses to environmental cues in Arabidopsis. AB - Plants adjust the timing of the transition to flowering to ensure their reproductive success in changing environments. Temperature and light are major environmental signals that affect flowering time through converging on the transcriptional regulation of FLOWERING LOCUS T (FT) encoding the florigen in Arabidopsis. Here, we show that a MYB transcription factor EARLY FLOWERING MYB PROTEIN (EFM) plays an important role in directly repressing FT expression in the leaf vasculature. EFM mediates the effect of ambient temperature on flowering and is directly promoted by another major FT repressor, SHORT VEGETATIVE PHASE. EFM interacts with an H3K36me2 demethylase JMJ30, which forms a negative feedback regulatory loop with the light-responsive circadian clock, to specifically demethylate an active mark H3K36me2 at FT. Our results suggest that EFM is an important convergence point that mediates plant responses to temperature and light to determine the timing of reproduction. PMID- 25132386 TI - Genomic instability, driver genes and cell selection: Projections from cancer to stem cells. AB - Cancer cells and stem cells share many traits, including a tendency towards genomic instability. Human cancers exhibit tumor-specific genomic aberrations, which often affect their malignancy and drug response. During their culture propagation, human pluripotent stem cells (hPSCs) also acquire characteristic genomic aberrations, which may have significant impact on their molecular and cellular phenotypes. These aberrations vary in size from single nucleotide alterations to copy number alterations to whole chromosome gains. A prominent challenge in both cancer and stem cell research is to identify "driver aberrations" that confer a selection advantage, and "driver genes" that underlie the recurrence of these aberrations. Following principles that are already well established in cancer research, candidate driver genes have also been suggested in hPSCs. Experimental validation of the functional role of such candidates can uncover whether these are bona fide driver genes. The identification of driver genes may bring us closer to a mechanistic understanding of the genomic instability of stem cells. Guided by terminologies and methodologies commonly applied in cancer research, such understanding may have important ramifications for both stem cell and cancer biology. This article is part of a Special Issue entitled: Stress as a fundamental theme in cell plasticity. PMID- 25132387 TI - Interobserver variability of cervical cytology in HIV-infected women. AB - OBJECTIVES: Our objectives were to determine the reproducibility of cytological specimen interpretation between two pathologists in human immunodeficiency virus (HIV)-infected women (from the VIHGY, ANRS CO17 study of human papillomavirus genital pathology among HIV-positive women) and to analyse the improvement, if any, between conventional and liquid-based cytology (LBC) interpretations. MATERIALS AND METHODS: A sample of all abnormal and 40% of randomly selected normal Papanicolaou (Pap) tests was randomly ordered and read blindly by a second pathologist using the revised Bethesda terminology 2001. For both conventional and liquid-based preparations, unweighted and Cicchetti-Allison-weighted kappa and their 95% confidence intervals (CIs) were calculated. Kappa values were then compared using the Altman rule to classify the reproducibility of cytological specimen interpretation. RESULTS: Two hundred and seventy-seven conventional Pap tests were reviewed, including 79 abnormal and 10 unsatisfactory results. Overall agreement between the two observers was 78%, with an estimated Cicchetti-Allison weighted kappa of 0.69 (95%CI, 0.61-0.77). The corresponding values for the 268 LBCs, including 123 abnormal and two unsatisfactory results, were 84% and 0.82 (95%CI, 0.76-0.87), respectively. The reproducibility of LBC interpretations was significantly higher than that of conventional preparations (P = 0.009) and, for both laboratories, the percentages of unsatisfactory results were significantly lower for LBC. CONCLUSION: In HIV-infected women in the combination antiretroviral therapy era, the strength of agreement was better for LBCs than for conventional preparations, with a lower percentage of unsatisfactory results. When available, LBC should be preferred because of its higher reproducibility. PMID- 25132388 TI - Chronicling changes to the chronic disease prevention landscape in Canada's public health system 2004-2010. AB - The collective impact of major shifts in public health infrastructure and numerous new chronic disease prevention (CDP) capacity-building initiatives that have taken place in Canada over the last decade is unknown. The objective of this study was to determine if CDP capacity (i.e., skills and resources) and involvement in CDP programming improved in public health organizations in Canada from 2004 to 2010. Data for this repeated cross-sectional study were drawn from two waves of a national census of organizations mandated to carry out primary prevention of chronic disease and/or promotion of healthy eating, physical activity and tobacco control. Medians for continuous variables and frequencies for categorical variables were compared across time. Neither resources nor level of priority for CDP increased over time. There was little difference in the proportion of organizations with high levels of skills and involvement in core CDP practices (i.e., needs assessment, identification of relevant practices, planning, evaluation). Skills and involvement in CDP risk factor programming showed some gains, some steady states and some losses. Specifically, skill and involvement in tobacco control programming declined markedly while the proportion of organizations involved in healthy eating and physical activity programming increased. Skills to address and involvement in programming related to social determinants of health remained low over time as did involvement in programming addressing multiple risk factors concurrently. The lack of marked improvement in CDP capacity between 2004 and 2010 against a backdrop of initiatives favourable to strengthening the preventive health system in Canada suggests that efforts may have fallen short. PMID- 25132389 TI - Science and society: vaccines and public health. AB - Most public health research is devoted to the measurement of disease burdens and of the costs and effectiveness of control measures. The history of immunization provides many colourful examples of various ways in which such measurements are made, of how they have influenced policies, and of the importance of public perception of the magnitudes of the various burdens, benefits and risks. Improving the public's ability to evaluate evidence is itself an important aspect of public health. PMID- 25132391 TI - Social capital and immunization against the 2009 A(H1N1) pandemic in the American States. AB - The objective of this paper was to investigate the association between contextual social capital and immunization coverage rates. A cross-sectional, ecologic study design was used. Three different estimations of contextual social capital in American states have been used. Data on immunization coverage rates at state level comes from Centers for Disease Control and Prevention. Correlation coefficients were calculated to investigate the bivariate association between the independent variable social capital and the dependent variable 2009 A(H1N1) immunization coverage rates. A multivariate OLS regression model was used to investigate the association between contextual social capital and immunization, under control for state-level health care spending per capita, state population, population per square mile, and median age in the American States. Results show that Social capital was strongly correlated with 2009 A(H1N1) immunization acceptance among American States. In a multivariate regression analysis, the association remains strong and significant also when controlling state-level confounders. In conclusion, social capital, at least in a U.S. context, is shown to be associated with the state-level uptake of vaccination against the 2009 A(H1N1) pandemic. PMID- 25132390 TI - Measuring the burden of disease due to climate change and developing a forecast model in South Korea. AB - OBJECTIVES: Climate change influences human health in various ways, and quantitative assessments of the effect of climate change on health at national level are becoming essential for environmental health management. STUDY DESIGN: This study quantified the burden of disease attributable to climate change in Korea using disability-adjusted life years (DALY), and projected how this would change over time. METHODS: Diseases related to climate change in Korea were selected, and meteorological data for each risk factor of climate change were collected. Mortality was calculated, and a database of incidence and prevalence was established. After measuring the burden of each disease, the total burden of disease related to climate change was assessed by multiplying population attributable fractions. Finally, an estimation model for the burden of disease was built based on Korean climate data. RESULTS: The total burden of disease related to climate change in Korea was 6.85 DALY/1000 population in 2008. Cerebrovascular diseases induced by heat waves accounted for 72.1% of the total burden of disease (hypertensive disease 1.82 DALY/1000 population, ischaemic heart disease 1.56 DALY/1000 population, cerebrovascular disease 1.56 DALY/1000 population). According to the estimation model, the total burden of disease will be 11.48 DALY/1000 population in 2100, which is twice the total burden of disease in 2008. CONCLUSIONS: This study quantified the burden of disease caused by climate change in Korea, and provides valuable information for determining the priorities of environmental health policy in East Asian countries with similar climates. PMID- 25132392 TI - The effects of depression and chronic diseases on the work outcomes of employees: a prospective study in Northwest China. AB - A prospective cohort study was conducted to examine the impact of physical and mental health status on the job loss and job turnover rates in Northwestern China. There were 1778 employees included in the baseline survey at April 2006 and were followed-up in October 2006. They were classified into four groups: those with chronic diseases (n = 205), depression (n = 273), both chronic diseases and depression (n = 96), and a control group (n = 1204). Logistic regression was used to examine the impact of depression and chronic diseases on employment between the baseline and the 6-month follow-up interviews. The results of the analyses showed that participants suffering from depression were more likely to be unemployed (OR, 1.44; P < 0.05), recently changed jobs (OR, 3.28, P < 0.001) and earning a lower salary (B = -135.28RMB, P < 0.001). Depression accompanying chronic diseases had an increased risk of unemployment (OR, 2.05; P < 0.01). The participants with chronic diseases were more likely to change their jobs (OR, 2.53; P < 0.05), but this had no significant impact on unemployment and monthly salary. Overall, the findings suggest that people with depression were at a higher risk of unemployment and job turnover than people with chronic disease. PMID- 25132393 TI - Antibacterial usage in English NHS hospitals as part of a national Antimicrobial Stewardship Programme. AB - Antimicrobial resistance (AMR) has become a global problem for health care services, with fewer antimicrobials entering the market and some pathogenic organisms becoming resistant to commonly used antimicrobials. Antimicrobial stewardship (AS), including evidence-based standard setting, education and communication, and audits of practice, has become a key method of preventing the rise in the rise in AMR. Data on antibiotic consumption are often obtained through prospective and retrospective point prevalence audits of antibiotic usage, but such studies are very resource intensive and only provide a snapshot of consumption. The objective of the study reported here was to examine longitudinal total antibacterial usage at a national level and cross-sectional usage at an individual hospital trust level using a commercial database that captures antimicrobial prescribing from at least 99% of English hospital Trusts. PMID- 25132394 TI - Radiological predictors of cytoreductive outcomes in patients with advanced ovarian cancer. AB - OBJECTIVE: To assess site of disease on preoperative computed tomography (CT) to predict surgical debulking in patients with ovarian cancer. DESIGN: Two-phase retrospective cohort study. SETTING: West London Gynaecological Cancer Centre, UK. POPULATION: Women with stage 3 or 4, ovarian, fallopian or primary peritoneal cancer undergoing cytoreductive surgery. METHODS: Preoperative CT images were reviewed by experienced radiologists to assess the presence or absence of disease at predetermined sites. Multivariable stepwise logistic regression models determined sites of disease which were significantly associated with surgical outcomes in the test (n = 111) and validation (n = 70) sets. MAIN OUTCOME MEASURES: Sensitivity and specificity of CT in predicting surgical outcome. RESULTS: Stepwise logistic regression identified that the presence of lung metastasis, pleural effusion, deposits on the large-bowel mesentery and small bowel mesentery, and infrarenal para-aortic nodes were associated with debulking status. Logistic regression determined a surgical predictive score which was able to significantly predict suboptimal debulking (n = 94, P = 0.0001) with an area under the curve (AUC) of 0.749 (95% confidence interval [95% CI]: 0.652, 0.846) and a sensitivity of 69.2%, specificity of 71.4%, positive predictive value of 75.0% and negative predictive value of 65.2%. These results remained significant in a recent validation set. There was a significant difference in residual disease volume in the test and validation sets (P < 0.001) in keeping with improved optimal debulking rates. CONCLUSIONS: The presence of disease at some sites on preoperative CT scan is significantly associated with suboptimal debulking and may be an indication for a change in surgical planning. PMID- 25132395 TI - Osteoid osteoma of the phalanx and metacarpal bone: report of 17 cases. AB - BACKGROUND: Osteoid osteoma (OO) is a slowly progressing benign osteoblastic tumour. In the hand, this tumour is rare. We propose a review of seventeen cases of OO of the phalanx and metacarpal bone. PATIENTS AND METHODS: During the period, between 1998 and 2011, a total of seventeen OO in the hand were confirmed by the pathological examination. They were 10 women and 7 men with an average age of 29 years (age range 17-76). The most common site of the tumour was the proximal phalanx in ten cases, followed by middle phalanx in four cases and metacarpal bone in three cases. The diagnosis of OO was highly required by clinical history. Standard radiographs showed variable images, but computed tomography, and it was useful to facilitate diagnosis and pre-operative planning. All patients underwent surgery (the tumour resection and autogenous bone grafting). In post-operative, there was an immediate pain relief with complete resolution of all symptoms. No recurrence was observed during the last follow-up period of 4 years and 2 months. CONCLUSION: The diagnosis of OO of the hand can be difficult, and it should be considered with bony pain or bony swelling, especially when the history is a chronic one. The CT scan allows visualisation and precise localisation of such benign tumour of the hand. The care should be taken to make the excision complete in order to avoid recurrence. PMID- 25132396 TI - Use of structured expert judgment to forecast invasions by bighead and silver carp in Lake Erie. AB - Identifying which nonindigenous species will become invasive and forecasting the damage they will cause is difficult and presents a significant problem for natural resource management. Often, the data or resources necessary for ecological risk assessment are incomplete or absent, leaving environmental decision makers ill equipped to effectively manage valuable natural resources. Structured expert judgment (SEJ) is a mathematical and performance-based method of eliciting, weighting, and aggregating expert judgments. In contrast to other methods of eliciting and aggregating expert judgments (where, for example, equal weights may be assigned to experts), SEJ weights each expert on the basis of his or her statistical accuracy and informativeness through performance measurement on a set of calibration variables. We used SEJ to forecast impacts of nonindigenous Asian carp (Hypophthalmichthys spp.) in Lake Erie, where it is believed not to be established. Experts quantified Asian carp biomass, production, and consumption and their impact on 4 fish species if Asian carp were to become established. According to experts, in Lake Erie Asian carp have the potential to achieve biomass levels that are similar to the sum of biomasses for several fishes that are harvested commercially or recreationally. However, the impact of Asian carp on the biomass of these fishes was estimated by experts to be small, relative to long term average biomasses, with little uncertainty. Impacts of Asian carp in tributaries and on recreational activities, water quality, or other species were not addressed. SEJ can be used to quantify key uncertainties of invasion biology and also provide a decision-support tool when the necessary information for natural resource management and policy is not available. PMID- 25132397 TI - Interleukin-4 and granulocyte-macrophage colony-stimulating factor mediates the upregulation of soluble vascular endothelial growth factor receptor-1 in RAW264.7 cells-a process in which p38 mitogen-activated protein kinase signaling has an important role. AB - BACKGROUND/PURPOSE: Soluble vascular endothelial growth factor receptor-1 (sVEGFR1) antagonizes angiogenesis by inhibiting the biological function of vascular endothelial growth factor (VEGF). Immature dendritic cells (imDCs) express high levels of sVEGFR1 during development and are antiangiogenic. This study aimed to investigate the changes in VEGFR1, sVEGFR1, and VEGF levels during the development of imDCs and explore the underlying signaling mechanisms. METHODS: To model the differentiation of imDCs from monocytes, RAW264.7 cells, a murine monocyte/macrophage cell line, were stimulated by interleukin-4 (IL-4; 10 ng/mL, 20 ng/mL, and 40 ng/mL) and/or by granulocyte-macrophage colony stimulating factor (GM-CSF; 10 ng/mL, 20 ng/mL, and 50 ng/mL) and/or pretreated by the p38 inhibitor SB203580. The levels of VEGFR1, sVEGFR1, and VEGF were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blot, and enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-4 increased the VEGFR1 mRNA and sVEGFR1 levels in RAW264.7 (p < 0.05). This increase was inhibited by SB203580. Granulocyte-macrophage colony-stimulating factor increased the sVEGFR1 levels, but it had no significant effect on VEGFR1 mRNA levels. SB203580 decreased the expression of VEGFR1 mRNA induced by GM-CSF, whereas sVEGFR1 was unaffected. IL-4 had a greater effect on sVEGFR1 levels, compared to GM-CSF. CONCLUSION: IL-4 and GM-CSF increased sVEGFR1 levels, but did not significantly effect VEGF expression, and led to the antiangiogenesis properties of monocytes. p38 Mitogen-activated protein kinase signaling has an important role in the process. PMID- 25132398 TI - Comparison of three different techniques for the isolation of viral RNA in sputum. AB - BACKGROUND: Respiratory infections are a major cause of morbidity and mortality worldwide. A high percentage of all respiratory tract infections are caused by RNA viruses. Real-time PCR is a highly sensitive method for the detection of respiratory viruses in clinical samples. A good RNA isolation protocol is of high importance, since RNA is more unstable than DNA and many clinical samples contain RNAses. OBJECTIVES: To evaluate the performance of three different RNA extraction protocols for the extraction of respiratory viral RNA from sputum samples obtained from patients with the suspicion of a viral respiratory tract infection. STUDY DESIGN: A total of 50 sputum samples, PCR positive for a respiratory RNA virus, were used for viral RNA isolation with the phenol/chloroform method, RTP((r)) DNA/RNA virus mini kit and the automated MagNa Pure LC (MPLC) extraction system. After isolation, real-time PCR was performed for the detection of viral RNA in the sputum samples. RESULTS: The MPLC extraction increased the detection probability from 82% (phenol/chloroform) and 86% (RTP((r)) DNA/RNA virus mini kit) to 94%. In 16% the RTP((r)) DNA/RNA virus mini kit resulted in lower Ct values compared to the phenol/chloroform method, while in 32% the phenol/chloroform resulted in lower Ct values. CONCLUSIONS: The extraction of viral RNA performed with the MPLC extraction method was superior to the extraction with the RTP((r)) DNA/RNA virus mini kit and to the extraction with phenol/chloroform. In general, there was no difference in the detection of viral RNA between the phenol/chloroform extraction method and the RTP((r)) DNA/RNA virus mini kit. PMID- 25132400 TI - Family support in the transition to adulthood in Portugal--its effects on identity capital development, uncertainty management and psychological well being. AB - In a familistic southern European society such as the Portuguese, the family has historically played a prominent role in supporting the negotiation of transition pathways into adulthood. The present study aimed at capturing (1) the relative weight of parental financial support and autonomy support in contributing to the youngsters' psychological well-being (PWB), and (2) the mediating role of identity capital and uncertainty management in this relationship. A total of 620 participants completed measures of parental support, identity capital, uncertainty management and PWB. Autonomy support was found to be the strongest predictor of PWB, both directly and indirectly through its effects on identity capital and the use of target focused uncertainty management strategies. Conversely, financial support evidenced only a minor indirect impact through the mediation of tangible identity capital. Autonomy stimulation may constitute one of the most developmentally determinant family challenges in assisting the process of coming of age in Portugal. PMID- 25132399 TI - Evaluation of RT-PCR and immunohistochemistry as tools for detection of enterovirus in the human pancreas and islets of Langerhans. AB - BACKGROUND: Enteroviruses have been implicated in the etiology of type 1 diabetes, supported by immunoreactivity of enteroviral protein in islets, but presence of enteroviral genome has rarely been reported. Failure to detect enterovirus with RT-PCR has been attributed to the possible presence of PCR inhibitors and that only few cells are infected. OBJECTIVES: The aim of this study was to evaluate strategies for detection of enterovirus in human islets. STUDY DESIGN: A scenario was modeled with defined infected islets among a large number of uninfected pancreatic cells and the sensitivity of immunohistochemistry and PCR for detection of enterovirus was evaluated. RESULTS: Enterovirus was detected with PCR when only one single human islet, infected in vitro with a low dose of virus, was mixed with an uninfected pancreatic biopsy. Enterovirus could not be detected by immunohistochemistry under the same conditions, demonstrating the superior sensitivity of PCR also in pancreatic tissue with only a small fraction of infected cells. In addition, we demonstrate that pancreatic cell culture supernatant does not cause degradation of enterovirus at 37 degrees C, indicating that under normal culture conditions released virus is readily detectable. Utilizing PCR, the pancreases of two organ donors that died at onset of type 1 diabetes were found negative for enterovirus genome despite islet cells being positive using immunohistochemistry. CONCLUSIONS: These data suggest that PCR should be the preferred screening method for enterovirus in the pancreas and suggest cautious interpretation of immunostaining for enterovirus that cannot be confirmed with PCR. PMID- 25132401 TI - Serum hsCRP and procalcitonin levels in dyspeptic patients infected with CagA positive Helicobacter pylori. PMID- 25132402 TI - The status of 25-hydroxyvitamin D across the spectrum of glucose tolerance among middle-aged and elderly Chinese individuals. AB - CONTEXT: Although vitamin D status and its inverse association with diabetes among White people have been recognized, little research on vitamin D status has been well conducted in Chinese individuals based on glucose tolerance. OBJECTIVE: To compare the vitamin D status of Chinese individuals aged 40-75 years based on the glucose tolerance status. DESIGN AND METHODS: Serum 25OHD was measured in a cross-sectional sample of 10 038 individuals aged 40-75 years from Lanzhou city, which is located in western China. RESULTS: People with normal glucose tolerance (NGT, n = 4744), prediabetes (n = 2808) or diabetes (n = 2486) aged 40-75 years were included in the study. The difference in 25OHD concentration between people with NGT and prediabetes was not significant (16.5 vs 16.0 ng/ml, P = 0.773), but the 25OHD concentration of diabetes was higher than that of subjects with NGT (16.5 vs 16.5 ng/ml, P = 0.025) and prediabetes (16.5 vs 16.0 ng/ml, P = 0.032) after adjusting confounders. There was no difference in the prevalence of vitamin D deficiency between people with NGT and diabetes (74.7% vs 74.0%, P = 0.535), but the prevalence of vitamin D deficiency of prediabetes was higher than that of people with NGT (77.0% vs 74.7%, P = 0.024) and diabetes (77.0% vs 74.0%, P = 0.012). CONCLUSIONS: Although vitamin D status was significantly different across the spectrum of glucose tolerance in middle-aged and elderly Chinese individuals, the difference was not clinically significant. The results, however, highlight the very high prevalence of vitamin D deficiency in this population and should raise the awareness of this important public health issue among health-care providers. PMID- 25132403 TI - SIRT1 directly regulates SOX2 to maintain self-renewal and multipotency in bone marrow-derived mesenchymal stem cells. AB - SOX2 is crucial for the maintenance of the self-renewal capacity and multipotency of mesenchymal stem cells (MSCs); however, the mechanism by which SOX2 is regulated remains unclear. Here, we report that RNA interference of sirtuin 1 (SIRT1) in human bone marrow (BM)-derived MSCs leads to a decrease of SOX2 protein, resulting in the deterioration of the self-renewal and differentiation capacities of BM-MSCs. Using immunoprecipitation, we demonstrated direct binding between SIRT1 and SOX2 in HeLa cells overexpressing SOX2. We further discovered that the RNA interference of SIRT1 induces the acetylation, nuclear export, and ubiquitination of SOX2, leading to proteasomal degradation in BM-MSCs. SOX2 suppression by trichostatin A (TSA), a known histone deacetylase inhibitor, was reverted by treatment with resveratrol (0.1 and 1 uM), a known activator of SIRT1 in BM-MSCs. Furthermore, 0.1 and 1 uM resveratrol reduced TSA-mediated acetylation and ubiquitination of SOX2 in BM-MSCs. SIRT1 activation by resveratrol enhanced the colony-forming ability and differentiation potential to osteogenic and adipogenic lineages in a dose-dependent manner. However, the enhancement of self-renewal and multipotency by resveratrol was significantly decreased to basal levels by RNA interference of SOX2. These results strongly suggest that the SIRT1-SOX2 axis plays an important role in maintaining the self renewal capability and multipotency of BM-MSCs. In conclusion, our findings provide evidence for positive SOX2 regulation by post-translational modification in BM-MSCs through the inhibition of nuclear export and subsequent ubiquitination, and demonstrate that SIRT1-mediated deacetylation contributes to maintaining SOX2 protein in the nucleus. PMID- 25132404 TI - Linking oxygen availability with membrane potential maintenance and K+ retention of barley roots: implications for waterlogging stress tolerance. AB - Oxygen deprivation is a key determinant of root growth and functioning under waterlogging. In this work, changes in net K(+) flux and membrane potential (MP) of root cells were measured from elongation and mature zones of two barley varieties under hypoxia and anoxia conditions in the medium, and as influenced by ability to transport O2 from the shoot. We show that O2 deprivation results in an immediate K(+) loss from roots, in a tissue- and time-specific manner, affecting root K(+) homeostasis. Both anoxia and hypoxia induced transient membrane depolarization; the extent of this depolarization varied depending on severity of O2 stress and was less pronounced in a waterlogging-tolerant variety. Intact roots of barley were capable of maintaining H(+) -pumping activity under hypoxic conditions while disrupting O2 transport from shoot to root resulted in more pronounced membrane depolarization under O2 -limited conditions and in anoxia a rapid loss of the cell viability. It is concluded that the ability of root cells to maintain MP and cytosolic K(+) homeostasis is central to plant performance under waterlogging, and efficient O2 transport from the shoot may enable operation of the plasma membrane H(+) -ATPase in roots even under conditions of severe O2 limitation in the soil solution. PMID- 25132405 TI - Baicalein induces autophagic cell death through AMPK/ULK1 activation and downregulation of mTORC1 complex components in human cancer cells. AB - Baicalein, a flavonoid and aglycon hydrolyzed from baicalin, has anticancer properties in several human carcinomas, but its molecular mechanisms of action remain unclear. Here, we show that baicalein leads to human cancer cell death by inducing autophagy rather than apoptosis, because cell death induced by baicalein was completely reversed by suppressing the expression levels of key molecules in autophagy such as Beclin 1, vacuolar protein sorting 34 (Vps34), autophagy related (Atg)5 and Atg7, but not by pan-caspase inhibitor. Our data revealed that baicalein significantly increased the number of green fluorescence protein cytosol-associated protein light chain 3 (GFP-LC3)-containing puncta and LC3B-II expression levels, which were further enhanced by chloroquine treatment. Furthermore, a luciferase-based reporter assay showed that the ratio of RLuc LC3wt/RLuc-LC3G120A was greatly reduced. The data suggested that baicalein induced not only autophagosome formation, but also autophagic flux. Experiments using short interfering RNAs and pharmacological inhibitors revealed that Beclin 1, Vps34, Atg5, Atg7 and UNC-51 (Caenorhabditis elegans)-like kinase 1 (ULK1) play pivotal roles in mediating baicalein-induced autophagy. Moreover, baicalein activated AMP-activated protein kinase (AMPK)alpha, leading to ULK1 activation through phosphorylation at Ser555, whereas both protein and mRNA levels of mammalian target of rapamycin (mTOR) and Raptor, upstream inhibitors of ULK1 and autophagy, were markedly downregulated by baicalein. Our data suggest that the anticancer effects of baicalein are mainly due to autophagic cell death through activation of the AMPK/ULK1 pathway and inhibition of mTOR/Raptor complex 1 expression. These results provide new mechanistic insights into the anticancer functions of autophagy inducers, such as baicalein, which may be used as potential therapeutics for cancer treatment. PMID- 25132406 TI - Prevalence of peri-implant inflammatory disease in patients with a history of periodontal disease who receive supportive periodontal therapy. AB - OBJECTIVES: To describe the status of implants in periodontally compromised patients who regularly receive supportive periodontal therapy (SPT) and to determine the factors associated to peri-implant inflammatory disease in those patients. MATERIAL AND METHODS: Clinical and radiographic data of implants in periodontal patients who, after being treated and included in a SPT programme, wore implant prostheses for at least 6 months were recorded. The implants were classified according to the criteria of the 6th European Workshop on Periodontology in health, mucositis and peri-implantitis. Logistic regression analysis was performed to analyse the individual and adjusted effects of each study variable on mucositis or peri-implantitis, using SUDAAN to account for clustering (multiple implants within the patient). RESULTS: A total of 786 implants were placed in 239 patients. At patient level, 60.3%, 24.7% and 15.1% were classified as healthy, mucositis and peri-implantitis patients, respectively. At implant level, the respective percentages were 77.4%, 12.8% and 9.8%. For mucositis, at implant level, the adjusted ORs indicate a significant association with plaque index (P = 0.050), type of periodontitis (P = 0.030) and location (P = 0.045). For peri-implantitis, the adjusted ORs indicate a significant association with plaque index (P < 0.001) and location (P = 0.002). CONCLUSIONS: The prevalence of peri-implant inflammatory disease in periodontal patients who regularly undergo SPT is clinically significant. The factors associated with peri-implant inflammatory disease were plaque index and implant location, and mucositis was also affected by the type of periodontitis the patient had. PMID- 25132407 TI - Comprehensive hands-on training for influenza vaccine manufacturing: a WHO-BARDA BTEC partnership for global workforce development. AB - The critical need for enhancing influenza pandemic preparedness in many developing nations has led the World Health Organization (WHO) and the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services (HHS), to develop an international influenza vaccine capacity-building program. Among the critical limitations faced by many of these nations is lack of access to training programs for staff supporting operations within vaccine production facilities. With support from BARDA, the Biomanufacturing Training and Education Center (BTEC) at North Carolina State University has addressed this need for training by developing and delivering a comprehensive training program, consisting of three courses: Fundamentals of cGMP Influenza Vaccine Manufacturing, Advanced Upstream Processes for Influenza Vaccine Manufacturing, and Advanced Downstream Processes for Influenza Vaccine Manufacturing. The courses cover process design, transfer, and execution at manufacturing scale, quality systems, and regulations covering both manufacturing and approval of pandemic vaccines. The Fundamentals course focuses on the concepts, equipment, applicable regulations, and procedures commonly used to produce influenza vaccine. The two Advanced courses focus on process design, scale up, validation, and new technologies likely to improve efficiency of vaccine production. All three courses rely on a combination of classroom instruction and hands-on training in BTEC's various laboratories. Each course stands alone, and participants may take one or more of the three courses. Overall participant satisfaction with the courses has been high, and follow-up surveys show that participants actively transferred the knowledge they gained to the workplace. Future plans call for BTEC to continue offering the three courses and to create an online version of several modules of the Fundamentals course. PMID- 25132408 TI - The sensory world of fish and fisheries: impact of human activities--an international conference to evaluate the effects of environmental changes on the sensory world of fish/aquatic animals and fisheries. PMID- 25132409 TI - Looking deeper than (just) below the surface: response. PMID- 25132410 TI - Research review: Polygenic methods and their application to psychiatric traits. AB - BACKGROUND: Despite evidence from twin and family studies for an important contribution of genetic factors to both childhood and adult onset psychiatric disorders, identifying robustly associated specific DNA variants has proved challenging. In the pregenomics era the genetic architecture (number, frequency and effect size of risk variants) of complex genetic disorders was unknown. Empirical evidence for the genetic architecture of psychiatric disorders is emerging from the genetic studies of the last 5 years. METHODS AND SCOPE: We review the methods investigating the polygenic nature of complex disorders. We provide mini-guides to genomic profile (or polygenic) risk scoring and to estimation of variance (or heritability) from common SNPs; a glossary of key terms is also provided. We review results of applications of the methods to psychiatric disorders and related traits and consider how these methods inform on missing heritability, hidden heritability and still-missing heritability. FINDINGS: Genome-wide genotyping and sequencing studies are providing evidence that psychiatric disorders are truly polygenic, that is they have a genetic architecture of many genetic variants, including risk variants that are both common and rare in the population. Sample sizes published to date are mostly underpowered to detect effect sizes of the magnitude presented by nature, and these effect sizes may be constrained by the biological validity of the diagnostic constructs. CONCLUSIONS: Increasing the sample size for genome wide association studies of psychiatric disorders will lead to the identification of more associated genetic variants, as already found for schizophrenia. These loci provide the starting point of functional analyses that might eventually lead to new prevention and treatment options and to improved biological validity of diagnostic constructs. Polygenic analyses will contribute further to our understanding of complex genetic traits as sample sizes increase and as sample resources become richer in phenotypic descriptors, both in terms of clinical symptoms and of nongenetic risk factors. PMID- 25132412 TI - Successful management of chronic postsurgical pain following total knee replacement. AB - We report reversal of chronic postsurgical pain (CPSP) along with functional restoration after total knee replacement (TKR) in two patients, using a combination therapy that included ultrasonography-guided pulsed radiofrequency (PRF) of nerves supplying the knee to provide pain relief, along with dry needling (DN) to relax myofascial triggers/bands that caused painful stiffness and restricted movement of muscles acting across the knee. Both patients showed demonstrable pain relief, as evidenced by changes in pain as assessed on the Numeric Rating Scale (patient 1: 4-9/10 [pre-treatment] to 0-3/10 [6 months post treatment]; patient 2: 5-9/10 to 0-4/10), Oxford Knee Score (patient 1: 17 to 40; patient 2: 12 to 39), Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs score (patient 1: 16 to 0; patient 2: 18 to 0), and Patient Health Questionnaire-9 score (patient 1: 17 to 2; patient 2: 20 to 2). The selection of the PRF-and-DN combination for treating post-TKR CPSP was based on a new idea that CPSP is a neuromyopathic phenomenon involving both sensory and motor neuropathy. It has evolved from our experience of 8 years. Physiotherapy worked synergistically with DN, optimizing muscle performance and pain relief. PMID- 25132411 TI - Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). AB - BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, demonstrated efficacy and safety in moderate-to-severe plaque psoriasis when administered via subcutaneous injection. Self-administration by pre-filled syringe (PFS) can offer patients clinical benefits of a drug, with increased convenience. OBJECTIVES: To assess efficacy, safety and usability of secukinumab administration via PFS in subjects with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: Subjects in this phase 3 trial were randomized 1 : 1 : 1 to secukinumab 300 or 150 mg or matching placebo. Results to week 12 are presented here. Each treatment was delivered using a PFS once weekly to week 4, and again at week 8. Co-primary endpoints were secukinumab superiority over placebo for week 12 PASI 75 (>= 75% reduction in Psoriasis Area and Severity Index) and IGA mod 2011 (2011 modified Investigator's Global Assessment) 0/1 response rates. Secondary endpoints included PFS usability, determined by observer rating of successful, hazard-free self-injection and subject rating of acceptability by the Self-Injection Assessment Questionnaire (SIAQ). RESULTS: Co primary endpoints were met, with demonstration of superiority for each secukinumab dose vs. placebo at week 12 (PASI 75: 75.9%, 69.5% and 0% for secukinumab 300 mg, 150 mg and placebo; IGA mod 2011 0/1: 69.0%, 52.5% and 0%, respectively; P < 0.0001 for all comparisons vs. placebo). PFS usability was high: 100% of subjects successfully self-administered treatment at week 1, and subjects reported high SIAQ-assessed acceptability of the PFS throughout the trial. No new/unexpected safety signals were observed. CONCLUSIONS: Secukinumab administration by PFS was effective, with an acceptable safety profile and high usability. The PFS provides a reliable, convenient form of secukinumab administration in subjects with moderate-to-severe plaque psoriasis. PMID- 25132413 TI - Microextraction sample preparation techniques in biomedical analysis. AB - Biologically active compounds are found in biological samples at relatively low concentration levels. The sample preparation of target compounds from biological, pharmaceutical, environmental, and food matrices is one of the most time consuming steps in the analytical procedure. The microextraction techniques are dominant. Metabolomic studies also require application of proper analytical technique for the determination of endogenic metabolites present in biological matrix on trace concentration levels. Due to the reproducibility of data, precision, relatively low cost of the appropriate analysis, simplicity of the determination, and the possibility of direct combination of those techniques with other methods (combination types on-line and off-line), they have become the most widespread in routine determinations. Additionally, sample pretreatment procedures have to be more selective, cheap, quick, and environmentally friendly. This review summarizes the current achievements and applications of microextraction techniques. The main aim is to deal with the utilization of different types of sorbents for microextraction and emphasize the use of new synthesized sorbents as well as to bring together studies concerning the systematic approach to method development. This review is dedicated to the description of microextraction techniques and their application in biomedical analysis. PMID- 25132414 TI - Beyond the use of modifiers in selective alkyne hydrogenation: silver and gold nanocatalysts in flow mode for sustainable alkene production. AB - We report on the excellent stereo and chemoselectivity of nanosized silver and gold catalysts in the three-phase hydrogenation of acetylenic compounds under flow chemistry conditions. The materials featuring metal nanoparticles in the range of 2-21 nm were prepared by spray deposition or incipient wetness impregnation of silver nitrate and sol immobilisation of gold chloride on different carriers (Al2O3, SiO2, TiO2, and carbon), followed by activation in various atmospheres. The samples were characterised by ICP-OES, N2 sorption, XPS, HAADF-STEM, and HRTEM, and evaluated in a continuous-flow flooded-bed micro reactor. Both metals display optimal activities for particles below 5 nm, enabling stable operation at T = 373 K and P = 10 bar. While the performance of the silver catalysts is less influenced by the support, the gold nanoparticles exhibit significant activity only when deposited on TiO2, likely due to the strong metal-support interaction. Hydrogenations of functionalised alkynes reveal that silver and gold match, and in some cases exceed, the selectivity of benchmark palladium-based catalysts. Furthermore, in contrast to Pd, the Ag and Au samples require no modifiers, which brings fundamental and practical simplifications for their understanding and large scale manufacture. Therefore, these materials could be advantageously used for the continuous production of olefinic intermediates in the fine chemical and pharmaceutical industries. PMID- 25132415 TI - Communicating developmental psychobiology to the masses: why psychobiologists should contribute to Wikipedia. PMID- 25132416 TI - Breast vs. the rest: a response to Koczwara and Ward. PMID- 25132417 TI - Determination of rifampicin in rat plasma by modified large-volume direct injection RAM-HPLC and its application to a pharmcokinetic study. AB - A direct large volume injection high-performance liquid chromatography (HPLC) method with homemade restricted-access media (RAM) pre-column and combined with a column-switching valve was established and developed for determination rifampicin (RIP) in rat plasma. The rat plasma samples (100 MUL) were injected directly onto pre-column, where RIP was retained and pre-concentrated, while proteins were washed to waste using a methanol-water (5:95) as the mobile phase at a flow rate of 1 mL/min. Then, by rotation of the switching valve at 5 min, the RIP were eluted from the pre-column and transferred to an Luna C18 analytical column by the chromatographic mobile phase consisting of methanol-acetonitrile-10 mm ammonium format (60:5:35) at a flow rate of 1 mL/min. The total analytical run time was 15 min with UV detection wavelength at 254 nm. Carbamazepine was used as the internal standard. Excellent linear correlation (r = 0.9993) was obtained in the range of 0.25-8 ug/mL for rat plasma. The intra-day and inter-day precisions of RIP were all <5.0%. The recoveries were in the range of from 99.98-113.66% for plasma. This on-line RAM-HPLC method was successfully applied to the pharmacokinetic study of RIP in rat plasma. PMID- 25132418 TI - Increased proliferation and decreased membrane permeability as defense mechanisms of Fusobacterium nucleatum against human neutrophilic peptide-1. AB - Human neutrophilic peptides (HNPs) constitute a class of host defense molecules, which contribute to the non-oxidative killing of bacteria and other microorganisms. Since the adaptability is crucial to bacterial survival in changing environments, it is of interest to know how Fusobacterium nucleatum, the major bridge organism connecting early and late colonizers in dental biofilms, defends itself against HNPs. This study aimed to examine the planktonic growth, membrane permeability, and biofilm formation characteristics as defense mechanisms of F. nucleatum against HNP-1. In all experiments, the type strain of F. nucleatum (ssp. nucleatum ATCC 25586) and two clinical strains (ssp. nucleatum AHN 9508 and ssp. polymorphum AHN 9910) were used. Planktonic growth (measured in colony forming units), capsular polysaccharide production (visualized by Ziehl Neelsen stain), membrane permeability (demonstrated as N-phenyl-1-naphthylamine uptake), biofilm formation, and established biofilm development (measured as total mass and polysaccharide levels) were analyzed in the presence of 0 MUg/ml (control), 1 MUg/ml, 5 MUg/ml, and 10 MUg/ml of HNP-1. Planktonic growth of the strains AHN 9508 and ATCC 25586 were significantly (p<0.05) increased in the presence of HNP-1, while their membrane permeability decreased (p<0.005) in the planktonic form. HNP-1 decreased the biofilm formation of the strains ATCC 25586 and AHN 9910, whereas it increased the growth of the strain AHN 9508 in established biofilms. Capsule formation and polysaccharide production were not observed in any strain. We conclude that the inhibition of the membrane permeability and the increase in planktonic and established biofilm growth could act as bacterial defense mechanisms against neutrophilic defensins. In addition, this strain-dependent survival ability against HNP-1 may explain the variation in the virulence of different F. nucleatum strains. PMID- 25132419 TI - Diagnosis, management and outcome of early anastomotic leakage following colorectal anastomosis using a compression device: is it different? AB - AIM: Compression anastomosis has proved to be safe for rectal reconstruction with leak rates comparable to those observed using circular stapling devices. However, there are no data on whether the metallic compression ring alters the ease of diagnosis or the treatment in cases of leakage. In this study, we present our experience with early leakage following compression anastomosis. METHOD: A prospective registry was used for data review. Patients with anastomotic leakage following compression anastomosis between November 2008 and September 2013 were included. RESULTS: In all, 197 (92 female) patients were operated using a novel compression device. Early leakage was found in 10 (5.1%) patients after a median of 5 (3-14) days. The radiologist was able to detect leakage using CT in nine out of 10 cases unequivocally. Removal of the ring was necessary in eight of the 10 cases, and salvage of the anastomosis was feasible on six occasions. In all diverted cases with a low anastomosis, a transanal repair of the defect was feasible in three cases, including a single patient with complete separation of the anastomosis. CONCLUSION: Artefacts on the CT scan caused by the compression ring did not hamper the diagnosis of anastomotic leakage. Removal of the ring in the early postoperative period is not associated with complete separation of the bowel ends. Salvage of anastomosis is feasible in most cases. PMID- 25132420 TI - Dye-sensitized solar cell from polyaniline-ZnS nanotubes and its characterization through impedance spectroscopy. AB - Polyaniline (PANI)-zinc sulphide (ZnS) nanocomposites (PAZs) are synthesized by polymerizing aniline in the presence of acetic acid with different concentrations of ZnS nanoparticles (NPs). FESEM and TEM images indicate the nanotube morphology of PANI and ZnS NPs remain adhered to the nanotube surface, but at higher ZnS concentration the nanotube morphology is lost. UV-vis spectra indicate PANI is in the doped state and the doping increases with an increase in ZnS concentration. Fluorescence intensity passes through a minimum with ZnS content and the dc conductivity of the composites gradually increases with an increase in ZnS NP concentration. The I-V plot of PAZ composites indicates that the photocurrent is higher than that of the dark current at each voltage, and the device exhibits reversible turning "on" and "off" by switching the white light illumination "on" and "off". Dye-sensitized solar cells fabricated with PAZ composites display a reasonably higher power conversion efficiency (eta = 3.38%) than pure ZnS NPs. An attempt is made to shed light on the operating mechanism of the DSSC from the impedance data using a Cole-Cole plot by drawing an equivalent circuit illustrating the different electronic and ionic transport processes within the cell. PMID- 25132421 TI - A metal-free strategy to release chemisorbed H2 from hydrogenated boron nitride nanotubes. AB - Chemisorbed hydrogen on boron nitride nanotubes (BNNT) can only be released thermally at very high temperatures above 350 degrees C. However, no catalyst has been identified that could liberate H2 from hydrogenated BN nanotubes under moderate conditions. Using different density functional methods we predict that the desorption of chemisorbed hydrogen from hydrogenated BN nanotubes can be facilitated catalytically by triflic acid at low free-energy activation barriers and appreciable rates under metal free conditions and mildly elevated temperatures (40-50 degrees C). Our proposed mechanism shows that the acid is regenerated in the process and can further facilitate similar catalytic release of H2 , thus suggesting all the chemisorbed hydrogen on the surface of the hydrogenated nanotube can be released in the form of H2 . These findings essentially raise hope for the development of a sustainable chemical hydrogen storage strategy in BN nanomaterials. PMID- 25132422 TI - An analysis of genetic factors related to risk of inflammatory bowel disease and colon cancer. AB - BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci are also associated with colon cancer risk. METHODS: We selected 15 validated SNPs associated with risk of either Crohn's disease, ulcerative colitis, or both in previous GWAS and tested whether these loci were also associated with colon cancer risk in a two-stage study design. RESULTS: We found that rs744166 in STAT3 was associated with colon cancer risk in two studies; however, the direction of the observation was reversed in TP53 mutant tumors possibly due to a nullification of the effect by mutant p53. The SNP, which lies within intron 1 of the STAT3 gene, was associated with lower expression of STAT3 mRNA in TP53 wild type, but not mutant, tumors. CONCLUSIONS: These data suggest that the STAT3 locus is associated with both IBD and cancer. Further understanding the function of this variant in relation to TP53 could possibly explain the role of this gene in autoimmunity and cancer. Furthermore, an analysis of this locus, specifically in a population with IBD, could help to resolve the relationship between this SNP and cancer. PMID- 25132424 TI - The growth response of ostrich (Struthio camelus var. domesticus) chicks fed on diets with three different dietary protein and amino acid concentrations. AB - 1. Feeding costs are the largest expense in an ostrich production system, and protein is one of the more expensive components of the diet. This study evaluated the growth response of ostrich chicks on diets containing different concentrations of protein (amino acids). The diets were formulated to contain three concentrations of protein (one diet with 20% less protein than the conventional concentration, L; one diet with the conventional concentration of protein, M and one diet with 20% more protein than the conventional concentration, H) for each of the phase diets. The phase diets were pre-starter, starter, grower and finisher. 2. This study includes the analysis of ostrich body weight (BW) by modelling growth with linear polynomial and non-linear functions for all the data not separated for treatments. In total, 3378 BW recordings of 90 animals were collected weekly from hatch (d 0) to 287 d (41 weeks) of age. 3. Seven non-linear growth models and three linear polynomial models were fitted to the data. The growth functions were compared by using Akaike's information criterion (AIC). For the non-linear models, the Bridges and Janoschek models had the lowest AIC values for the H treatment, while the Richards curve had the lowest value for M and the von Bertalanffy for the L treatment. 4. For the linear polynomial models, the linear polynomial of the third degree had the lowest AIC values for all three treatments, thus making it the most suitable model for the data; therefore, the predictions of this model were used to interpret the growth data. Significant differences were found between treatments for growth data. 5. The results from this study can aid in describing the growth of ostriches subjected to optimum feeding conditions. This information can also be used in research when modelling the nutrient requirements of growing birds. PMID- 25132423 TI - Completeness and validity in a national clinical thyroid cancer database: DATHYRCA. AB - BACKGROUND: Although a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid cancer database: DATHYRCA. STUDY DESIGN AND SETTING: National prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used to appraise the validity. For validity assessment 100 cases were randomly selected from the DATHYRCA database; medical records were used as a reference. RESULT: The database held 1934 cases of thyroid carcinoma and completeness of case ascertainment was estimated to 90.9%. Completeness of registration was around or above 90% in most instances. Perfect agreement on the diagnosis of thyroid carcinoma was found, both inter- and intra-observer, and kappa values of selected variables showed overall good to excellent agreement. CONCLUSION: In a setup with public health insurance, personal identity numbers and extended governmental databases, it is possible to establish national clinical cancer databases with a satisfactory completeness and validity. The DATHYRCA database is considered reliable in terms of describing thyroid carcinoma at a national level. PMID- 25132425 TI - Clinical evaluation of ezetimibe on bile lithogenicity in humans: Use of transnasal endoscopy for bile sampling. AB - AIM: Ezetimibe inhibits cholesterol absorption by blocking Niemann-Pick C1-like 1 proteins (NPC1L1) expressed in the small intestine. Because NPC1L1 is also expressed in human liver, ezetimibe conceivably alters biliary lipid compositions. Here, we performed a clinical trial investigating the effect of ezetimibe on biliary lipids using transnasal endoscopy for bile collection. METHODS: Eight patients with dyslipidemia enrolled in this study completed blood and bile sampling before and at 3 months after ezetimibe treatment (10 mg/day), and the samples are analyzed. RESULTS: Endoscopic bile sampling was performed safely and painlessly. Serum sterol-based biomarkers declared decreased cholesterol absorption and increased synthesis. On analysis of biliary lipids, four of the eight patients showed relative decrease of cholesterol and increase of bile acids with improved lithogenicity while the remainder exhibited the symmetrical changes. CONCLUSION: Our data suggests that biliary lithogenicity is not worsened by ezetimibe. The regulation of biliary cholesterol is presumably multifactorial such as body cholesterol pool size and biliary cholesterol reabsorption by NPC1L1 in the liver. PMID- 25132426 TI - Who benefits most from Head Start? Using latent class moderation to examine differential treatment effects. AB - Head Start (HS) is the largest federally funded preschool program for disadvantaged children. Research has shown relatively small impacts on cognitive and social skills; therefore, some have questioned its effectiveness. Using data from the Head Start Impact Study (3-year-old cohort; N = 2,449), latent class analysis was used to (a) identify subgroups of children defined by baseline characteristics of their home environment and caregiver and (b) test whether the effects of HS on cognitive, and behavioral and relationship skills over 2 years differed across subgroups. The results suggest that the effectiveness of HS varies quite substantially. For some children there appears to be a significant, and in some cases, long-term, positive impact. For others there is little to no effect. PMID- 25132428 TI - Cytogenetic studies and their prognostic contribution in 565 Chinese patients with primary myelofibrosis. AB - To study the feature and prognostic contribution of cytogenetic information in Chinese patients with primary myelofibrosis (PMF), we analyzed cytogenetic data from 565 patients with PMF. One hundred and sixty-two subjects (29%) had abnormal karyotypes, including trisomy 8 (45; 28%), deletion of 20q (25; 15%), deletion of 13q (13; 8%), deletion of 11q (12; 7%), and abnormal chromosome 1 (21; 13%); balanced translocations (14; 9%); a complex karyotype (CK; 30; 19%), and a monosomal karyotype (MK; 19; 12%). Using these data, we showed that the Dynamic International Prognostic Scoring System (DIPSS)-plus, which includes cytogenetic information, is a better survival predictor than the DIPSS. We next used our data to construct the following two cytogenetic-based cohorts: (1) favorable karyotype subjects with a normal karyotype, a CK that is not a MK, +8 only or a balanced translocation only and (2) unfavorable karyotype-all others. The median survival times were not reached and were 52 month (95% CI, 32-72 months; P = 0.01) in patients with favorable and unfavorable karyotypes, respectively. These data provided the detailed cytogenetic information in Chinese patients with PMF and confirmed the impact of cytogenetic abnormalities on survival in Chinese patients. PMID- 25132427 TI - Controlled-rate freezing to regulate the structure of collagen-glycosaminoglycan scaffolds in engineered skin substitutes. AB - Controlled-rate freezing (CRF) of biopolymer scaffolds may increase reproducibility of microstructure compared with analog processes. Freezing of collagen-glycosaminoglycan (CG) scaffolds by CRF with liquid nitrogen at chamber cooling rates of -80, -40, -20, or -10 degrees C/min, was compared with submersion in 95% ethanol at -55 degrees C. Cooling rates of -80 or -40 degrees C/min generated scaffolds with pore areas and pore fractions that were comparable to scaffolds frozen in ethanol. Test and control scaffolds were populated with human dermal fibroblasts and epidermal keratinocytes to generate engineered skin substitutes (ESS) and evaluated for surface hydration and mitochondrial metabolism. ESS with scaffolds frozen by CRF at -80 or -40 degrees C/min were comparable with, or better than, ESS with control scaffolds (p < 0.05). These results demonstrate that fabrication of CG scaffolds by CRF offers advantages of digital programming, as well as greater reproducibility, safety, and simplicity than submersion in chilled ethanol without compromise of biological properties required for biomedical applications. PMID- 25132430 TI - Fever, diarrhoea and buttock pain in a 15-year-old female traveller (case presentation). PMID- 25132431 TI - Editor's comments. PMID- 25132432 TI - Fever, diarrhoea and buttock pain in a 15-year-old female traveller (discussion and diagnosis). PMID- 25132433 TI - [Cancer Plan 3 and molecular pathology: serendipity in pathology?]. PMID- 25132434 TI - [The Canadian Association of Pathology guidelines for establishing a diagnostic telepathology service using whole-slide imaging]. PMID- 25132435 TI - [Pathology of gallbladder and extrahepatic bile ducts. Introduction]. PMID- 25132438 TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 1. Alcalculous gangrenous cholecystitis]. PMID- 25132439 TI - [Pathology of the gallbladder and extra-hepatic bile ducts. Cases 2 and 3. Chronic cholecystitis]. PMID- 25132440 TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 4. Sclerosing lymphoplasmacytic cholecystitis]. PMID- 25132441 TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 5. Clear cell vesicular adenocarcinoma, pT1bNx stage (TNM, 7th edition)]. PMID- 25132442 TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 6. Well- differentiated hilar cholangiocarcinoma pT2bN1]. PMID- 25132443 TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 7. Biliary-type tubulopapillary adenoma without dysplasia]. PMID- 25132444 TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 8. Intraductal papillary neoplasm of extrahepatic bile duct without invasive carcinoma (WHO 2010), with high-grade intraepithelial neoplasia/carcinoma in situ (pTisNx, TNM 7th edition): "Dysplastic degenerated biliary papillomatosis, but non-invasive"]. PMID- 25132445 TI - [A painful occipital mass revealing a posterior encephalocele]. AB - Encephalocele is a congenital malformation caused by a neural tube defect during embryonic development. We report a case of posterior encephalocele in a 7-month old infant with a painful occipital mass known since birth. Pathological examination of the mass showed different mature tissues derived from the brain and its coverings (e.g., neuroglia, ependymal canals and clusters of meningothelial cells). A diagnosis of encephalocele was made. The different forms of neural tube defect will be briefly discussed, especially the "aborted" forms (e.g., non-specific midline mass lesion or angioma) that the pathologist may encounter in his/her daily practice. PMID- 25132446 TI - [Systemic EBV+ T-cell lymphoproliferative disease of childhood]. AB - Systemic EBV+ T-cell lymphoproliferative disease of childhood is a recent entity described in the 2008 World Health Organisation tumours of haematopoietic system and lymphoid tissues as a clonal T-cell EBV+ systemic proliferation. It occurs after acute or chronic active EBV infection. We report the case of a caucasian, immunocompetent 12-year-old girl, with no particular history, who presented with hemophagocytic lymphohistiocytosis in the aftermath of an infectious mononucleosis. Main symptoms were multiple organ failure, hepatosplenomegaly and pancytopenia. Histopathology of peripheral lymph node and bone marrow revealed a T-cell, CD8+, EBV+ lymphoproliferation. An elevated viral load was detected in blood by PCR. The patient died within 3 weeks. Since most of the cases have been reported in Asia and South America, few cases still have been described in Europe. Unlike B-cell lymphoproliferation in immunocompromised individuals, T cell EBV+ lymphoproliferation occurs in immunocompetent patients and seems to be the consequence of a proliferative disorder of EBV-infected T-cells, attributed to a cytotoxic T-cell response deficiency. These T-cell proliferations are more frequently immunoreactive for CD8 than CD4. A key feature of the diagnosis might be EBV viral load. PMID- 25132447 TI - [An unusual renal arterial lesion]. PMID- 25132449 TI - Identification of putative kdr mutations in the tropical bed bug, Cimex hemipterus (Hemiptera: Cimicidae). AB - BACKGROUND: Bed bugs [both Cimex hemipterus (F.) and Cimex lectularius L.] are highly resistant to pyrethroids worldwide. An important resistance mechanism known as 'knockdown resistance' (kdr) is caused by genetic point mutations on the voltage-gated sodium channel (VGSC) gene. Previous studies have identified two point mutations (V419L and L925I) on the VGSC gene in C. lectularius that are responsible for kdr-type resistance. However, the kdr mutations in C. hemipterus have not been investigated. RESULTS: Four novel mutations, L899V (leucine to valine), M918I (methionine to isoleucine), D953G (aspartic acid to glycine) and L1014F (leucine to phenylalanine), were identified in the domain II region of the C. hemipterus VGSC gene. This region has been widely investigated for the study of kdr-type resistance to pyrethroids in other insect pests. The V419L and L925I kdr mutations as previously identified in C. lectularius were not detected in C. hemipterus. CONCLUSION: M918I and L1014F are considered to be probable kdr mutations and may play essential roles in kdr-type resistance to pyrethroids in C. hemipterus. Further studies are under way in the authors' laboratory to determine the non-kdr-type resistance mechanisms in C. hemipterus. PMID- 25132450 TI - Implementing skin-to-skin contact in the operating room following cesarean birth. AB - Immediate skin-to-skin contact (SSC) after birth benefits the health of mothers and newborns by increasing breastfeeding rates, stabilizing the newborn's temperature, and encouraging bonding (Moore, Anderson, Bergman, & Dowswell, 2012). Although immediate SSC after a vaginal birth was common practice at our hospital, it was rare in the operating room (OR) following a cesarean birth. To address this practice problem, we conducted a project to evaluate the feasibility of implementing SSC in the OR. PMID- 25132448 TI - Mutations in NOTCH1 cause Adams-Oliver syndrome. AB - Notch signaling determines and reinforces cell fate in bilaterally symmetric multicellular eukaryotes. Despite the involvement of Notch in many key developmental systems, human mutations in Notch signaling components have mainly been described in disorders with vascular and bone effects. Here, we report five heterozygous NOTCH1 variants in unrelated individuals with Adams-Oliver syndrome (AOS), a rare disease with major features of aplasia cutis of the scalp and terminal transverse limb defects. Using whole-genome sequencing in a cohort of 11 families lacking mutations in the four genes with known roles in AOS pathology (ARHGAP31, RBPJ, DOCK6, and EOGT), we found a heterozygous de novo 85 kb deletion spanning the NOTCH1 5' region and three coding variants (c.1285T>C [p.Cys429Arg], c.4487G>A [p.Cys1496Tyr], and c.5965G>A [p.Asp1989Asn]), two of which are de novo, in four unrelated probands. In a fifth family, we identified a heterozygous canonical splice-site variant (c.743-1 G>T) in an affected father and daughter. These variants were not present in 5,077 in-house control genomes or in public databases. In keeping with the prominent developmental role described for Notch1 in mouse vasculature, we observed cardiac and multiple vascular defects in four of the five families. We propose that the limb and scalp defects might also be due to a vasculopathy in NOTCH1-related AOS. Our results suggest that mutations in NOTCH1 are the most common cause of AOS and add to a growing list of human diseases that have a vascular and/or bony component and are caused by alterations in the Notch signaling pathway. PMID- 25132451 TI - Development of a fluoride chronic effects benchmark for aquatic life in freshwater. AB - Canada has an interim water-quality guideline for fluoride for protection of freshwater aquatic life that dates from 2002, and 1 Canadian province has a different interim water-quality guideline for fluoride that dates to 1995. The United States does not have a national benchmark for fluoride in freshwater, and only 1 US state has such a benchmark. There are no other national or regional benchmarks for fluoride chronic toxicity in freshwater. In the present study, available data on the acute and chronic toxicity of fluoride to freshwater aquatic life were compiled and reviewed. Acute toxicity was reported to occur at concentrations ranging from 11.5 to >800 mg/L fluoride (F(-) ). The majority of chronic effects occur at concentrations between 1.8 mg/L and 195 mg/L. A total of 10 chronic studies representing 16 species (5 fish, 7 invertebrates, and 4 algae/aquatic plants) were used to derive a chronic effects benchmark of 1.94 mg/L F(-) , applying the species sensitivity distribution approach. PMID- 25132452 TI - A B-1a cell subset induces Foxp3(-) T cells with regulatory activity through an IL-10-independent pathway. AB - Regulatory T (Treg) cells play a critical role in the maintenance of tolerance. B 1a cells belong to a specific and functionally important B-cell subset that exerts its regulatory role through the production of IL-10. While IL-10 has been correlated with the induction of type 1 Treg (Tr1) cells or Tr1-like cells, whether IL-10-producing B-1a cells are able to induce Treg cells, especially the Tr1 lineage, is poorly understood. We have demonstrated that, similar to the reported B-2 cells, B-1a cells are able to convert naive CD4(+)CD25(-) T cells into a subset of T cells with suppressive function, which we called 'Treg-of-B1a' cells. Treg-of-B1a cells do not express Foxp3, but upregulate the Treg markers OX40, programmed death 1 (PD-1), inducible costimulator (ICOS) and IL-10R. Moreover, Treg-of-B1a cells do not express Foxp3 and produce high levels of IFN gamma and IL-10, but minimal amounts of IL-4; therefore, they resemble Tr1 cells. However, utilizing IL-10(-/-) mice, we showed that IL-10 was not involved in the induction of Treg-of-B1a cells. On the contrary, CD86-mediated costimulation was essential for B-1a cells to drive the induction of Treg-of-B1a cells. Finally, we demonstrated that, in contrast to the Treg cells generated by B-2 cells that mediate contact-dependent suppression, Treg-of-B1a cells suppress through secreting soluble factors. While Tr1 cells mediate suppression mainly through IL 10 or TGF-beta secretion, Treg-of-B1a cells mediate suppression through an IL-10- and TGF-beta-independent pathway. Together, these findings suggest that B-1a cells induce a functionally and phenotypically distinct Treg population that is dissimilar to the reported Foxp3(+) Treg or Tr1 cells. PMID- 25132453 TI - Adrenomedullin and endocrine control of immune cells during pregnancy. AB - The immunology of pregnancy is complex and incompletely understood. Aberrant immune activity in the decidua and in the placenta is believed to play a role in diseases of pregnancy, such as infertility, miscarriage, fetal growth restriction and preeclampsia. Here, we briefly review the endocrine control of uterine natural killer cell populations and their functions by the peptide hormone adrenomedullin. Studies in genetic animal models have revealed the critical importance of adrenomedullin dosage at the maternal-fetal interface, with cells from both the maternal and fetal compartments contributing to essential aspects underlying appropriate uterine receptivity, implantation and vascular remodeling of spiral arteries. These basic insights into the crosstalk between the endocrine and immune systems within the maternal-fetal interface may ultimately translate to a better understanding of the functions and consequences of dysregulated adrenomedullin levels in clinically complicated pregnancies. PMID- 25132455 TI - Practical knowledge of experienced nurses in critical care: a qualitative study of their narratives. AB - BACKGROUND: Scholars of nursing practices have claimed practical knowledge is source of knowledge in its own right, nevertheless we know little about this knowledge associated with day-to-day practice. The purpose of this study is to describe knowledge that the more experienced nurses the in ICU make use of and discover the components of care it includes. Understanding this knowledge can contribute to improving the working practices of nurses with less experience. METHODS: We used a phenomenologic and hermeneutic approach to conduct a qualitative study. Open in-depth dialogue interviews were conducted with 13 experienced ICU nurses selected by intentional sampling. Data was compiled on significant stories of their practice. The data analysis enabled units of meaning to be categorised and grouped into topics regarding everyday practical knowledge. RESULTS: Knowledge related to everyday practice was evaluated and grouped into seven topics corresponding to how the ICU nurses understand their patient care: 1) Connecting with, calming and situating patients who cannot communicate; 2) Situating and providing relief to patients in transitions of mechanical respiration and non-invasive ventilation; 3) Providing reassurance and guaranteeing the safety of immobilised patients; 4) The "connection" with patients in comas; 5) Taking care of the body; 6) The transition from saving life to palliative care; and 7) How to protect and defend the patient from errors. The components of caretaking that guarantee success include: the calm, care and affection with which they do things; the time devoted to understanding, situating and comforting patients and families; and the commitment they take on with new staff and doctors for the benefit of the patient. CONCLUSIONS: These results show that stories of experiences describe a contextual practical knowledge that the more experienced nurses develop as a natural and spontaneous response. In critical patients the application of everyday practical knowledge greatly influences their well-being. In those cases in which the nurses describe how they have protected the patients from error, this practical knowledge can mean the difference between life and death. The study highlights the need to manage practical knowledge and undertake further research. The study is useful in keeping clinical practice up-to-date. PMID- 25132456 TI - Desiccation enhances phosphorylation of PSII and affects the distribution of protein complexes in the thylakoid membrane. AB - Desiccation has significant effects on photosynthetic processes in intertidal macro-algae. We studied an intertidal macro-alga, Ulva sp., which can tolerate desiccation, to investigate changes in photosynthetic performance and the components and structure of thylakoid membrane proteins in response to desiccation. Our results demonstrate that photosystem II (PSII) is more sensitive to desiccation than photosystem I (PSI) in Ulva sp. Comparative proteomics of the thylakoid membrane proteins at different levels of desiccation suggested that there were few changes in the content of proteins involved in photosynthesis during desiccation. Interestingly, we found that both the PSII subunit, PsbS (Photosystem II S subunit) (a four-helix protein in the LHC superfamily), and light-harvesting complex stress-related (LHCSR) proteins, which are required for non-photochemical quenching in land plants and algae, respectively, were present under both normal and desiccation conditions and both increased slightly during desiccation. In addition, the results of immunoblot analysis suggested that the phosphorylation of PSII and LHCII increases during desiccation. To investigate further, we separated out a supercomplex formed during desiccation by blue native polyacrylamide gel electrophoresis and identified the components by mass spectrometry analysis. Our results show that phosphorylation of the complex increases slightly with decreased water content. All the results suggest that during the course of desiccation, few changes occur in the content of thylakoid membrane proteins, but a rearrangement of the protein complex occurs in the intertidal macro-alga Ulva sp. PMID- 25132454 TI - The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies? AB - While the host immune response following primary human cytomegalovirus (HCMV) infection is generally effective at stopping virus replication and dissemination, virus is never cleared by the host and like all herpesviruses, persists for life. At least in part, this persistence is known to be facilitated by the ability of HCMV to establish latency in myeloid cells in which infection is essentially silent with, importantly, a total lack of new virus production. However, although the viral transcription programme during latency is much suppressed, a number of viral genes are expressed during latent infection at the protein level and many of these have been shown to have profound effects on the latent cell and its environment. Intriguingly, many of these latency-associated genes are also expressed during lytic infection. Therefore, why the same potent host immune responses generated during lytic infection to these viral gene products are not recognized during latency, thereby allowing clearance of latently infected cells, is far from clear. Reactivation from latency is also a major cause of HCMV mediated disease, particularly in the immune compromised and immune naive, and is also likely to be a major source of virus in chronic subclinical HCMV infection which has been suggested to be associated with long-term diseases such as atherosclerosis and some neoplasias. Consequently, understanding latency and why latently infected cells appear to be immunoprivileged is crucial for an understanding of the pathogenesis of HCMV and may help to design strategies to eliminate latent virus reservoirs, at least in certain clinical settings. PMID- 25132458 TI - Group-IV nanosheets with vacancies: a tight-binding extended Huckel study. AB - In this work, we present a theoretical study of the electronic properties of group-IV element nanosheets, namely graphene, silicene, germanene and the corresponding hydrogenated structures for the two latter, silicane and germanane. We compare the results of two different calculation methods, Density Functional Theory (DFT) and Extended Huckel Theory (EHT), for both pristine sheets and sheets of silicene and germanene with a single-atom vacancy. We show that EHT offers a remarkably reliable description of the electronic structure of these materials for all cases, thus offering an affordable way for studying large systems for which DFT calculations would be expensive and lengthy. PMID- 25132457 TI - Vitamin D deficiency decreases adiposity in rats and causes altered expression of uncoupling proteins and steroid receptor coactivator3. AB - The vitamin D endocrine system is functional in the adipose tissue, as demonstrated in vitro, in cultured adipocytes, and in vivo in mutant mice that developed altered lipid metabolism and fat storage in the absence of either 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] or the vitamin D receptor. The aim of the present study was to examine the role of vitamin D and calcium on body adiposity in a diet-induced vitamin D deficient rat model. Vitamin D-deficient rats gained less weight and had lower amounts of visceral fat. Consistent with reduced adipose tissue mass, the vitamin D-deficient rats had low circulating levels of leptin, which reflects body fat stores. Expression of vitamin D and calcium sensing receptors, and that of genes involved in adipogenesis such as peroxisome proliferator-activated receptor, fatty acid synthase and leptin were significantly reduced in white adipose tissue of deficient rats compared to vitamin D-sufficient rats. Furthermore, the expression of uncoupling proteins (Ucp1 and Ucp2) was elevated in the white adipose tissue of the deficient rat indicative of higher energy expenditure, thereby leading to a lean phenotype. Expression of the p160 steroid receptor coactivator3 (SRC3), a key regulator of adipogenesis in white adipose tissue was decreased in vitamin D-deficient state. Interestingly, most of the changes observed in vitamin D deficient rats were corrected by calcium supplementation alone. Our data demonstrates that dietary vitamin D and calcium regulate adipose tissue function and metabolism. PMID- 25132460 TI - Mapping support policies for informal carers across the European Union. AB - BACKGROUND: At a time when health and social care services in European countries are under pressure to contain or cut costs, informal carers are relied upon as the main providers of long-term care. However, still little is known about the availability of direct and indirect support for informal carers across the European Union. METHODS: Primary data collection in all EU member states was supplemented with an extensive review of the available literature. RESULTS: Various forms and levels of support have been implemented across Europe to facilitate the role of informal caregivers. Financial support is the most common type of support provided, followed by respite care and training. Most countries do not have a process in place to systematically identify informal carers and to assess their needs. Policies are often at an early stage of development and the breadth of support varies significantly across the EU. CONCLUSIONS: Policy developments are uneven across the member states, with some countries having mechanisms in place to assess the needs and support informal carers while others are only starting to take an interest in developing support services. Given the unprecedented challenges posed by population ageing, further research and better data are needed to capture and monitor information on informal carers, to help design adequate support policies and eventually to evaluate their impact across the EU. PMID- 25132459 TI - Intravenous infusion of paracetamol for intrapartum analgesia. AB - AIM: To evaluate the efficacy and adverse effects of an i.v. infusion of paracetamol during the active phase of labor as compared with sterile water (placebo) as a method for intrapartum analgesia. METHODS: In a triple-blind, randomized, placebo-controlled trial, 120 low-risk primiparous women presenting in active labor at Ain Shams University Maternity Hospital, Cairo, Egypt, between August 2011 and October 2012, were allocated to receive either 1000 mg i.v. of paracetamol (n = 60) or sterile water (n = 60). The primary outcomes were the efficacy of the drug to supply adequate analgesia as measured by a change in the visual analog scale (VAS) pain intensity score at various time points after drug administration and the need for additional rescue analgesia. The secondary outcomes included the presence of adverse maternal or fetal events. RESULTS: Compared to controls, i.v. infusion of paracetamol was associated with significantly lower VAS score 15 and 30 min after the start of medication; also, there was a significantly lower incidence of need for rescue medication (8/57 [14%] vs 49/59 [83.1%], P < 0.001) at 60 min after the start of medication. There were no recorded maternal adverse effects in either group. There were no differences in occurrence of intrapartum fetal distress or neonatal Apgar scores between both groups. CONCLUSION: Paracetamol appears to be a safe and effective medicine that can be used during the intrapartum period. PMID- 25132461 TI - Is benzoyl peroxide 3% topical gel effective and safe in the treatment of acne vulgaris in Japanese patients? A multicenter, randomized, double-blind, vehicle controlled, parallel-group study. AB - Benzoyl peroxide (BPO) as an anti-acne medication is not yet approved in Japan. This study evaluated the efficacy and safety of a once-daily topical application of BPO 3% gel versus an inert vehicle gel in Japanese acne patients. Three hundred and sixty patients were randomized to receive BPO 3% or vehicle for 12 weeks. The primary efficacy end-point was absolute change in number of total lesions (TL) from baseline to week 12 to demonstrate the superiority of BPO 3% versus vehicle. Secondary efficacy end-points were absolute and percent change in TL, inflammatory lesions (IL), non-inflammatory lesions (non-IL) and Investigator's Static Global Assessment (ISGA). Change in TL counts from baseline to week 12 for BPO 3% was superior to vehicle (difference, -21.0; P < 0.001). Absolute and percent reductions in TL, IL and non-IL counts were greater for BPO 3% at all study visits. The proportion of patients with improvement in ISGA scores was significantly higher with BPO 3% than with vehicle from week 2. All adverse events were mild or moderate. Adverse drug-related reactions were higher for BPO 3% (30%) than with vehicle (5%). Local tolerability scores of grade 1 or more (slight to moderate) were more frequent with BPO 3% than vehicle with the most significant differences observed in dryness (56% vs 27% at week 1-4), peeling (19% vs 9% at week 1-2) and burning/stinging (58% vs 15% at week 1-12). These results indicate that BPO 3% is effective while maintaining a favorable safety and tolerability profile in Japanese acne patients. PMID- 25132462 TI - Same-day discharge is feasible and safe in patients undergoing minimally invasive staging for gynecologic malignancies. AB - OBJECTIVE: The objective of the study was to evaluate the feasibility and safety of same-day discharge of patients undergoing minimally invasive comprehensive surgical staging for endometrial and cervical cancer. STUDY DESIGN: We performed a retrospective review of consecutive patients from January 2008 to December 2011 undergoing comprehensive staging for endometrial or cervical cancer by traditional laparoscopy or robotic-assisted laparoscopy and intended for same-day discharge. Patients accomplishing same-day discharge were compared with those who required admission. Clinical and demographic data, perioperative outcomes, and postoperative patient contacts within 6 weeks were collected. Multivariate logistic regression modeling was used to determine factors associated with admission and unscheduled patient contacts within 2 weeks of surgery. RESULTS: A total of 141 patients were identified. One hundred eighteen patients (83.7%) underwent same-day discharge and 23 (16.3%) required overnight admission. The variables that significantly predicted overnight admission were severe pain in the postanesthesia care unit (odds ratio [OR], 6.81; 95% confidence interval [CI], 1.74-26.6; P = .006), delayed ability to tolerate oral intake (OR, 9.3; 95% CI, 2.25-38.6, P = .002), traditional laparoscopic vs robotic-assisted surgical approach (OR, 9.05; 95% CI, 2.34-35.1; P = .001), and surgery start time at 2:00 pm or later (OR, 36.8; 95% CI, 6.19-219.3; P < .0001). There was no difference in the readmission rate between patients undergoing same-day discharge compared with overnight admission (11% vs 17%, P = .48). No variables significantly predicted unscheduled patient contact within 2 weeks of surgery at P < .01. CONCLUSION: Same-day discharge for patients undergoing laparoscopic or robotic-assisted laparoscopic staging for endometrial or cervical cancer is feasible and safe. There are low complication rates and few readmissions or unscheduled patient contacts within 2 weeks of surgery. PMID- 25132463 TI - Increased glucose and placental GLUT-1 in large infants of obese nondiabetic mothers. AB - OBJECTIVE: Obese women are at increased risk to deliver a large infant, however, the underlying mechanisms are poorly understood. Fetal glucose availability is critically dependent on placental transfer and is linked to fetal growth by regulating the release of fetal growth hormones such as insulin. We hypothesized that (1) umbilical vein glucose and insulin levels and (2) placental glucose transporter (GLUT) expression and activity are positively correlated with early pregnancy maternal body mass index and infant birthweight. STUDY DESIGN: Subjects in this prospective observational cohort study were nondiabetic predominantly Hispanic women delivered at term. Fasting maternal and umbilical vein glucose and insulin concentrations were determined in 29 women with varying early pregnancy body mass index (range, 18.0-54.3) who delivered infants with birthweights ranging from 2800-4402 g. We isolated syncytiotrophoblast microvillous and basal plasma membranes from 33 placentas and determined the expression of GLUT-1 and -9 (Western blot) and glucose uptake (radiolabeled glucose). RESULTS: Birthweight was positively correlated with umbilical vein glucose and insulin and maternal body mass index. Umbilical vein glucose levels were positively correlated with placental weight and maternal body mass index, but not with maternal fasting glucose. Basal plasma membranes GLUT-1 expression was positively correlated with birthweight. In contrast, syncytiotrophoblast microvillous GLUT-1 and -9, basal plasma membranes GLUT-9 expression and syncytiotrophoblast microvillous and basal plasma membranes glucose transport activity were not correlated with birthweight. CONCLUSION: Because maternal fasting glucose levels and placental glucose transport capacity were not increased in obese women delivering larger infants, we speculate that increased placental size promotes glucose delivery to these fetuses. PMID- 25132464 TI - Sonography-guided hydrostatic reduction of ileocolic intussusception in children: analysis of failure and success in consecutive patients presenting timely to the hospital. AB - In children with ileocolic intussusception sonography is increasingly being used for diagnosis, whereas fluoroscopy is frequently used for guiding non-invasive reduction. This study assessed the success rate of radiation-free sonography guided hydrostatic reduction in children with ileocolic intussusception, using novel well-defined success rate indices. All children were evaluated who presented from 2005 to 2013 to the local university hospital with ileocolic intussusception. The patients were treated with sonography-guided hydrostatic reduction unless primary surgery was clinically indicated. The according success rate was determined by indices of Bekdash et al. They represent the ratio of persistently successful non-surgical reductions versus four different denominators, depending on including/excluding cases with primary surgery and including/excluding cases requiring bowel resection/intervention. Fifty-six consecutive patients were included (age, 3 months to 7.8 years). About 80% of the patients presented until 24 h and 20% until 48 h after the onset of symptoms. Seven patients underwent primary surgery, with bowel resection required in three cases. Hydrostatic reduction was attempted in 49 patients, being permanently successful in 41 cases (selective reduction rate 41/49 = 83.7%; crude reduction rate 41/56 = 73.2%). The remaining eight patients underwent secondary surgery, with just two patients not requiring surgical bowel resection/intervention (corrected selective reduction rate 41/43 = 95.3%). The composite reduction rate was 87.2% (successful/feasible reductions, 41/47). CONCLUSION: Radiation-free sonography-guided hydrostatic reduction has a good success rate in children with ileocolic intussusception. It may be particularly valuable in centers that are already experienced with using sonography for the diagnosis. PMID- 25132465 TI - Binding isotope effects as a tool for distinguishing hydrophobic and hydrophilic binding sites of HIV-1 RT. AB - The current treatment for HIV-1 infected patients consists of a cocktail of inhibitors, in an attempt to improve the potency of the drugs by adding the possible effects of each supplied compound. In this contribution, nine different inhibitors of HIV-1 RT, one of the three key proteins responsible for the virus replication, have been selected to develop and test a computational protocol that allows getting a deep insight into the inhibitors' binding mechanism. The interaction between the inhibitors and the protein have been quantified by computing binding free energies through FEP calculations, while a more detailed characterization of the kind of inhibitor-protein interactions is based on frequency analysis of the ligands in the initial and final state, i.e. in solution and binding the protein. QM/MM calculation of heavy atoms ((13)C, (15)N, and (18)O) binding isotope effects (BIE) have been used to identify the binding sites of the different inhibitors. Specific interactions between the isotopically labeled atoms of the inhibitors and polar residues and magnesium cations on the hydrophilic pocket of the protein are responsible for the frequencies shifting that can be detected when comparing the IR spectra of the compounds in solution and in the protein. On the contrary, it seems that changes in vdW interactions from solution to the final state when the ligand is interacting with residues of the hydrophobic cavity, does not influence frequency modes and then no BIE are observed. Our results suggest that a proper computational protocol can be a valuable tool which in turn can be used to increase the efficiency of anti AIDS drugs. PMID- 25132466 TI - Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia. AB - Abnormal development can lead to deficits in adult brain function, a trajectory likely underlying adolescent-onset psychiatric conditions such as schizophrenia. Developmental manipulations yielding adult deficits in rodents provide an opportunity to explore mechanisms involved in a delayed emergence of anomalies driven by developmental alterations. Here we assessed whether oxidative stress during presymptomatic stages causes adult anomalies in rats with a neonatal ventral hippocampal lesion, a developmental rodent model useful for schizophrenia research. Juvenile and adolescent treatment with the antioxidant N-acetyl cysteine prevented the reduction of prefrontal parvalbumin interneuron activity observed in this model, as well as electrophysiological and behavioral deficits relevant to schizophrenia. Adolescent treatment with the glutathione peroxidase mimic ebselen also reversed behavioral deficits in this animal model. These findings suggest that presymptomatic oxidative stress yields abnormal adult brain function in a developmentally compromised brain, and highlight redox modulation as a potential target for early intervention. PMID- 25132467 TI - A common structure underlies low-frequency cortical dynamics in movement, sleep, and sedation. AB - Upper-limb movements are often composed of regular submovements, and neural correlates of submovement frequencies between 1 and 4 Hz have been found in the motor cortex. The temporal profile of movements is usually assumed to be determined by extrinsic factors such as limb biomechanics and feedback delays, but another possibility is that an intrinsic rhythmicity contributes to low frequencies in behavior. We used multielectrode recordings in monkeys performing an isometric movement task to reveal cyclic activity in primary motor cortex locked to submovements, and a distinct oscillation in premotor cortex. During ketamine sedation and natural sleep, cortical activity traversed similar cycles and became synchronized across areas. Because the same cortical dynamics are coupled to submovements and also observed in the absence of behavior, we conclude that the motor networks controlling the upper limb exhibit an intrinsic periodicity at submovement frequencies that is reflected in the speed profile of movements. PMID- 25132469 TI - TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. AB - Macrophages and microglia can be polarized along a continuum toward a detrimental (M1) or a beneficial (M2) state in the injured CNS. Although phagocytosis of myelin in vitro promotes M2 polarization, macrophage/microglia in the injured spinal cord retain a predominantly M1 state that is detrimental to recovery. We have identified two factors that underlie this skewing toward M1 polarization in the injured CNS. We show that TNF prevents phagocytosis-mediated conversion from M1 to M2 cells in vitro and in vivo in spinal cord injury (SCI). Additionally, iron that accumulates in macrophages in SCI increases TNF expression and the appearance of a macrophage population with a proinflammatory mixed M1/M2 phenotype. In addition, transplantation experiments show that increased loading of M2 macrophages with iron induces a rapid switch from M2 to M1 phenotype. The combined effect of this favors predominant and prolonged M1 macrophage polarization that is detrimental to recovery after SCI. PMID- 25132470 TI - Predictors of postoperative morbidity after laparoscopic versus open radical hysterectomy plus external beam radiotherapy: a propensity-matched comparison. AB - BACKGROUND: Identification of peri-operative variables predicting postoperative morbidity may improve postoperative patients' care. We aimed to identify patients' characteristics and operative factors predictive of early (<= 30-day) and late (<= 6-month) morbidity in cervical cancer patients undergoing surgery plus external beam radiotherapy (EBRT). METHODS: We studied 45 propensity-matched patient pairs (90 patients) undergoing laparoscopic radical hysterectomy (LRH) plus EBRT vs. abdominal radical hysterectomy (RAH) plus EBRT. Basic descriptive, multivariable and artificial neuronal network analyses (ANN) were used to design predicting models influencing outcomes. RESULTS: Baseline characteristics of the study populations were similar. Patients undergoing LRH experienced lower blood loss (200 (range, 10-700) vs. 400 (range, 100-2000) ml; P < 0.001), shorter length of hospital stay (4 (range, 1-10) vs. 8 (range, 5-52) days; P < 0.001) and similar operative time (235 (+/- 67.3) vs. 258 (+/- 70.2) min; P = 0.14) than patients undergoing RAH. We observed that, at multivariate analysis, open approach correlated with overall (OR: 1.2; 95%CI: 1.03-1.46), early (OR: 1.14; 95%CI:0.99-1.3) and late (OR: 1.13; 95%CI: 1.001-1.28) postoperative complications. CONCLUSIONS: Open approach is the main predictor for developing morbidity among cervical cancer patients undergoing radical hysterectomy followed by adjuvant radiotherapy. Laparoscopic surgery enhances peri-operative surgical results and minimizes the occurrence of late complications. PMID- 25132471 TI - Systemic toxicity related to metal hip prostheses. AB - INTRODUCTION: One in eight of all total hip replacements requires revision within 10 years, 60% because of wear-related complications. The bearing surfaces may be made of cobalt/chromium, stainless steel, ceramic, or polyethylene. Friction between bearing surfaces and corrosion of non-moving parts can result in increased local and systemic metal concentrations. OBJECTIVES: To identify and systematically review published reports of systemic toxicity attributed to metal released from hip implants and to propose criteria for the assessment of these patients. METHODS: Medline (from 1950) and Embase (from 1980) were searched to 28 February 2014 using the search terms (text/abstract) chrom* or cobalt* and [toxic* or intox* or poison* or adverse effect or complication] and [prosthes* or 'joint replacement' or hip or arthroplast*] and PubMed (all available years) was searched using the search term (("Chromium/adverse effects"[Mesh] OR "Chromium/poisoning"[Mesh] OR "Chromium/toxicity"[Mesh]) OR ("Cobalt/adverse effects"[Mesh] OR "Cobalt/poisoning"[Mesh] OR "Cobalt/toxicity"[Mesh])) AND ("Arthroplasty, Replacement, Hip"[Mesh] OR "Hip Prosthesis"[Mesh]). These searches identified 281 unique references, of which 23 contained original case data. Three further reports were identified from the bibliographies of these papers. As some cases were reported repeatedly the 26 papers described only 18 individual cases. Systemic toxicity. Ten of these eighteen patients had undergone revision from a ceramic-containing bearing to one containing a metal component. The other eight had metal-on-metal prostheses. Systemic toxicity was first manifest months and often several years after placement of the metal-containing joint. The reported systemic features fell into three main categories: neuro ocular toxicity (14 patients), cardiotoxicity (11 patients) and thyroid toxicity (9 patients). Neurotoxicity was manifest as peripheral neuropathy (8 cases), sensorineural hearing loss (7) and cognitive decline (5); ocular toxicity presented as visual impairment (6). All these neurological features, except cognitive decline, have been associated with cobalt poisoning previously. Type of prosthesis and blood metal concentrations. Where blood or serum metal concentrations were reported (n = 17 for cobalt and n = 14 for chromium), the median cobalt concentration was 398 (range, 13.6-6521) MUg/L and the median chromium concentration was 48 MUg/L (in whole blood) (range, 4.1-221 MUg/L including serum and blood values). Those patients reported to have systemic features who had received a metal-on-metal prosthesis (n = 8) had a median peak blood cobalt concentration of 34.5 (range, 13.6-398.6) MUg/L; those with a metal containing revision of a failed ceramic prosthesis (n = 10) had a median blood cobalt concentration of 506 (range, 353-6521) MUg/L. Management. The most common treatment was removal of the metal-containing prosthesis, undertaken in all but 2 patients. This was usually associated with a fall in circulating cobalt concentration and improvement in some or all features. Clinical and toxicological assessment of systemic features. We propose the following criteria for assessing the likelihood that clinical features are related to cobalt toxicity: clinical effects consistent with the known neurological, cardiac, or thyroidal effects of cobalt, and for which any other explanation is less likely; increased blood cobalt concentrations (substantially higher than those in patients with well functioning prostheses) several months after hip replacement; a fall in the blood cobalt concentration, usually accompanied by signs of improvement in features. When judged by these criteria, the systemic features in 10 of the reported cases are likely to be related to cobalt exposure from a metal-containing hip prosthesis. CONCLUSIONS: Rarely, patients exposed to high circulating concentrations of cobalt from failed hip replacements develop neurological damage, hypothyroidism and/or cardiomyopathy, which may not resolve completely even after removal of the prosthesis. The greatest risk of systemic cobalt toxicity seems to result from accelerated wear of a cobalt-containing revision of a failed ceramic prosthesis, rather than from primary failure of a metal-on-metal prosthesis. PMID- 25132468 TI - Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS. AB - A repeat expansion in C9ORF72 causes frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation, producing "c9RAN proteins." Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small-molecule binders of r(GGGGCC)exp. Chemical and enzymatic probing of r(GGGGCC)8 indicate that it adopts a hairpin structure in equilibrium with a quadruplex structure. Using this model, bioactive small molecules targeting r(GGGGCC)exp were designed and found to significantly inhibit RAN translation and foci formation in cultured cells expressing r(GGGGCC)66 and neurons transdifferentiated from fibroblasts of repeat expansion carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC)exp-binding small molecules as a possible c9FTD/ALS therapeutic and suggest that c9RAN proteins could potentially serve as a pharmacodynamic biomarker to assess efficacy of therapies that target r(GGGGCC)exp. PMID- 25132473 TI - Local lay rescuers with AEDs, alerted by text messages, contribute to early defibrillation in a Dutch out-of-hospital cardiac arrest dispatch system. AB - AIM: Public access defibrillation rarely reaches out-of-hospital cardiac arrest (OHCA) patients in residential areas. We developed a text message (TM) alert system, dispatching local lay rescuers (TM-responders). We analyzed the functioning of this system, focusing on response times and early defibrillation in relation to other responders. METHODS: In July 2013, 14112 TM-responders and 1550 automated external defibrillators (AEDs) were registered in a database residing with the dispatch center of two regions of the Netherlands. TM responders living <1000m radius of the patient received a TM to go to the patient directly, or were directed to retrieve an AED first. We analyzed 1536 OHCA patients where a defibrillator was connected from February 2010 until July 2013. Electrocardiograms from all defibrillators were analyzed for connection and defibrillation time. RESULTS: Of all OHCAs, the dispatcher activated the TM-alert system 893 times (58.1%). In 850 cases >=1 TM-responder received a TM-alert and in 738 cases >=1 AED was available. A TM-responder AED was connected in 184 of all OHCAs (12.0%), corresponding with 23.1% of all connected AEDs. Of all used TM responder AEDs, 87.5% were used in residential areas, compared to 71.6% of all other defibrillators. TM-responders with AEDs defibrillated mean 2:39 (min:sec) earlier compared to emergency medical services (median interval 8:00 [25-75th percentile, 6:35-9:49] vs. 10:39 [25-75th percentile, 8:18-13:23], P<0.001). Of all shocking TM-responder AEDs, 10.5% delivered a shock <=6min after call. CONCLUSION: A TM-alert system that includes local lay rescuers and AEDs contributes to earlier defibrillation in OHCA, particularly in residential areas. PMID- 25132474 TI - EuReCa ONE - ONE month - ONE Europe - ONE goal. PMID- 25132472 TI - Lymphatic fate specification: an ERK-controlled transcriptional program. AB - Lymphatic vessels are intimately involved in the regulation of water and solute homeostasis by returning interstitial fluid back to the venous circulation and play an equally important role in immune responses by providing avenues for immune cell transport. Defects in the lymphatic vasculature result in a number of pathological conditions, including lymphedema and lymphangiectasia. Knowledge of molecular mechanisms underlying lymphatic development and maintenance is therefore critical for understanding, prevention and treatment of lymphatic circulation-related diseases. Research in the past two decades has uncovered several key transcriptional factors (Prox1, Sox18 and Coup-TFII) controlling lymphatic fate specification. Most recently, ERK signaling has emerged as a critical regulator of this transcriptional program. This review summarizes our current understanding of lymphatic fate determination and its transcriptional controls. PMID- 25132475 TI - Therapeutic temperature management after cardiac arrest and the risk of bleeding: systematic review and meta-analysis. AB - AIM: Prognosis after cardiac arrest in the era of modern critical care is still poor with a high mortality of approximately 90%. Around 30% of the survivors have neurological impairments. Targeted temperature management (TTM) is the only treatment option which can improve mortality and neurological outcome. It is so far unclear if bleeding complications occur more often in patients undergoing TTM treatment. METHODS: We conducted a systematic literature research in September 2013 including three major databases i.e. MEDLINE, EMBASE and CENTRAL. All studies were rated in respect to the ILCOR Guidelines and concerning their level of evidence and quality. We then performed a meta-analysis on bleeding disposition under TTM. RESULTS: We initially found 941 studies out of which 34 matched our requirements and were thus included in our overview. Five studies including 599 patients were summarized in a meta-analysis concerning bleeding complications of all severities. There was a trend toward higher bleeding in patients treated with TTM (RR: 1.30, 95% CI: 0.97-1.74) which did not reach significance (p=0.085). Seven studies with an overall 599 patients were included in our meta-analysis on bleeding requiring transfusion. There was no significant difference in the incidence of severe bleeding with a risk ratio of 0.97 (95% CI: 0.61-1.56, p=0.909). CONCLUSIONS: The data included in our meta-analysis indicate that, concerning the risk of bleeding, TTM is a safe method for patients after cardiac arrest. We did not observe a significantly higher risk for bleeding in patients undergoing TTM. PMID- 25132476 TI - Reply to Letter: Adrenaline in out-of hospital cardiac arrest. PMID- 25132477 TI - Real-time video communication improves provider performance in a simulated neonatal resuscitation. AB - AIM: To determine if a real-time audiovisual link with a neonatologist, termed video-assisted resuscitation or VAR, improves provider performance during a simulated neonatal resuscitation scenario. METHODS: Using high-fidelity simulation, 46 study participants were presented with a neonatal resuscitation scenario. The control group performed independently, while the intervention group utilized VAR. Time to effective ventilation was compared using Wilcoxon rank sum tests. Providers' use of the corrective steps for ineffective ventilation per the NRP algorithm was compared using Cochran-Armitage trend tests. RESULTS: The time needed to establish effective ventilation was significantly reduced in the intervention group when compared to the control group (mean time 2 min 42 s versus 4 min 11 s, p<0.001). In the setting of ineffective ventilation, only 35% of control subjects used three or more of the first five corrective steps and none of them used all five steps. Providers in the control group most frequently neglected to open the mouth and increase positive pressure. In contrast, all of those in the intervention group used all of the first five corrective steps, p<0.001. All participants in the control group decided to intubate the infant to establish effective ventilation, compared to none in the intervention group, p<0.001. CONCLUSION: Using VAR during a simulated neonatal resuscitation scenario significantly reduces the time to establish effective ventilation and improves provider adherence to NRP guidelines. This technology may be a means for regional centers to support local providers during a neonatal emergency to improve patient safety and improve neonatal outcomes. PMID- 25132478 TI - Rhythm not ST elevation may be the key for post-resuscitation therapeutic success. PMID- 25132479 TI - Adrenaline in out-of hospital cardiac arrest. PMID- 25132480 TI - BRAF mutation testing in solid tumors: a methodological comparison. AB - Solid tumor genotyping has become standard of care for the characterization of proto-oncogene mutational status, which has traditionally been accomplished with Sanger sequencing. However, companion diagnostic assays and comparable laboratory developed tests are becoming increasingly popular, such as the cobas 4800 BRAF V600 Mutation Test and the INFINITI KRAS-BRAF assay, respectively. This study evaluates and validates the analytical performance of the INFINITI KRAS-BRAF assay and compares concordance of BRAF status with two reference assays, the cobas test and Sanger sequencing. DNA extraction from FFPE tissue specimens was performed followed by multiplex PCR amplification and fluorescent label incorporation using allele-specific primer extension. Hybridization to a microarray, signal detection, and analysis were then performed. The limits of detection were determined by testing dilutions of mutant BRAF alleles within wild type background DNA, and accuracy was calculated based on these results. The INFINITI KRAS-BRAF assay produced 100% concordance with the cobas test and Sanger sequencing and had sensitivity equivalent to the cobas assay. The INFINITI assay is repeatable with at least 95% accuracy in the detection of mutant and wild-type BRAF alleles. These results confirm that the INFINITI KRAS-BRAF assay is comparable to traditional sequencing and the Food and Drug Administration approved companion diagnostic assay for the detection of BRAF mutations. PMID- 25132483 TI - Postsacral vertebral morphology in relation to tail length among primates and other mammals. AB - Tail reduction/loss independently evolved in a number of mammalian lineages, including hominoid primates. One prerequisite to appropriately contextualizing its occurrence and understanding its significance is the ability to track evolutionary changes in tail length throughout the fossil record. However, to date, the bony correlates of tail length variation among living taxa have not been comprehensively examined. This study quantifies postsacral vertebral morphology among living primates and other mammals known to differ in relative tail length (RTL). Linear and angular measurements with known biomechanical significance were collected on the first, mid-, and transition proximal postsacral vertebrae, and their relationship with RTL was assessed using phylogenetic generalized least-squares regression methods. Compared to shorter tailed primates, longer-tailed primates possess a greater number of postsacral vertebral features associated with increased proximal tail flexibility (e.g., craniocaudally longer vertebral bodies), increased intervertebral body joint range of motion (e.g., more circularly shaped cranial articular surfaces), and increased leverage of tail musculature (e.g., longer spinous processes). These observations are corroborated by the comparative mammalian sample, which shows that distantly related short-tailed (e.g., Phascolarctos, Lynx) and long-tailed (e.g., Dendrolagus, Acinonyx) nonprimate mammals morphologically converge with short-tailed (e.g., Macaca tonkeana) and long-tailed (e.g., Macaca fascicularis) primates, respectively. Multivariate models demonstrate that the variables examined account for 70% (all mammals) to 94% (only primates) of the variance in RTL. Results of this study may be used to infer the tail lengths of extinct primates and other mammals, thereby improving our understanding about the evolution of tail reduction/loss. PMID- 25132482 TI - Real-time assessment of hybridization between wolves and dogs: combining noninvasive samples with ancestry informative markers. AB - Wolves and dogs provide a paradigmatic example of the ecological and conservation implications of hybridization events between wild and domesticated forms. However, our understanding of such implications has been traditionally hampered by both high genetic similarity and the difficulties in obtaining tissue samples (TS), which limit our ability to assess ongoing hybridization events. To assess the occurrence and extension of hybridization in a pack of wolf-dog hybrids in northwestern Iberia, we compared the power of 52 nuclear markers implemented on TS with a subset of 13 ancestry informative markers (AIMs) typed in noninvasive samples (NIS). We demonstrate that the 13 AIMs are as accurate as the 52 markers that were chosen without regard to the power to differentiate between wolves and dogs, also having the advantage of being rapidly screened on NIS. The efficiency of AIMs significantly outperformed ten random sets of similar size and an additional commercial set of 18 markers. Bayesian clustering analysis implemented on AIMs and NIS identified nine hybrids, two wolves and two dogs. Four hybrids were unambiguously assigned to F1xWolf backcrosses. Our approach (AIMs + NIS) overcomes previous difficulties related to sample availability and informative power of markers, allowing a quick identification of wolf-dog hybrids in the first phases of hybridization episodes. This provides managers with a reliable tool to evaluate hybridization and estimate the success of their actions. This approach may be easily adapted for other pairs of wild/domesticated species, thus improving our understanding of the introgression of domestication genes into natural populations. PMID- 25132481 TI - Haplotype counting by next-generation sequencing for ultrasensitive human DNA detection. AB - Human identity testing is critical to the fields of forensics, paternity, and hematopoietic stem cell transplantation. Most bone marrow (BM) engraftment testing currently uses microsatellites or short tandem repeats that are resolved by capillary electrophoresis. Single-nucleotide polymorphisms (SNPs) are theoretically a better choice among polymorphic DNA; however, ultrasensitive detection of SNPs using next-generation sequencing is currently not possible because of its inherently high error rate. We circumvent this problem by analyzing blocks of closely spaced SNPs, or haplotypes. As proof-of-principle, we chose the HLA-A locus because it is highly polymorphic and is already genotyped to select proper donors for BM transplant recipients. We aligned common HLA-A alleles and identified a region containing 18 closely spaced SNPs, flanked by nonpolymorphic DNA for primer placement. Analysis of cell line mixtures shows that the assay is accurate and precise, and has a lower limit of detection of approximately 0.01%. The BM from a series of hematopoietic stem cell transplantation patients who tested as all donor by short tandem repeat analysis demonstrated 0% to 1.5% patient DNA. Comprehensive analysis of the human genome using the 1000 Genomes database identified many additional loci that could be used for this purpose. This assay may prove useful to identify hematopoietic stem cell transplantation patients destined to relapse, microchimerism associated with solid organ transplantation, forensic applications, and possibly patient identification. PMID- 25132484 TI - Immune thrombocytopenia and alopecia areata: spontaneous occurrence and resolution in the same patient. AB - Alopecia areata (AA) and immune thrombocytopenia (ITP) are autoimmune conditions occasionally encountered by pediatricians, but their simultaneous occurrence is rare. We describe here a 7-year-old female who acutely developed both AA and ITP. Within 3 months both conditions resolved spontaneously, suggesting a pathophysiologic relationship. PMID- 25132485 TI - Water and temperature relations of soil Actinobacteria. AB - Actinobacteria perform essential functions within soils, and are dependent on available water to do so. We determined the water-activity (aw ) limits for cell division of Streptomyces albidoflavus, Streptomyces rectiviolaceus, Micromonospora grisea and Micromonospora (JCM 3050) over a range of temperatures, using culture media supplemented with a biologically permissive solute (glycerol). Each species grew optimally at 0.998 aw (control; no added glycerol) and growth rates were near-optimal in the range 0.971-0.974 (1 M glycerol) at permissive temperatures. Each was capable of cell division at 0.916-0.924 aw (2 M glycerol), but only S. albidoflavus grew at 0.895 or 0.897 aw (3 M glycerol, at 30 and 37 degrees C respectively). For S. albidoflavus, however, no growth occurred on media at <= 0.870 (4 M glycerol) during the 40-day assessment period, regardless of temperature, and a theoretical limit of 0.877 aw was derived by extrapolation of growth curves. This level of solute tolerance is high for non halophilic bacteria, but is consistent with reported limits for the growth and metabolic activities of soil microbes. The limit, within the range 0.895-0.870 aw , is very much inferior to those for obligately halophilic bacteria and extremely halophilic or xerophilic fungi, and is inconsistent with earlier reports of cell division at 0.500 aw . These findings are discussed in relation to planetary protection policy for space exploration and the microbiology of arid soils. PMID- 25132486 TI - Reply: Should we encourage exercise and sports in children and adolescents with cancer? PMID- 25132487 TI - Health governance in India: citizenship as situated practice. AB - Despite the impressive growth of the Indian economy over the past decades, the country struggles to deal with multiple and overlapping forms of inequality. One of the Indian government's main policy responses to this situation has been an increasing engagement with the 'rights regime', witnessed by the formulation of a plethora of rights-based laws as policy instruments. Important among these are the National Rural Health Mission (NRHM). Grounded in ethnographic research in Rajasthan focused on the management of maternal and child health under NRHM, this paper demonstrates how women, as mothers and health workers, organise themselves in relation to rights and identities. I argue that the rights of citizenship are not solely contingent upon the existence of legally guaranteed rights but also significantly on the social conditions that make their effective exercise possible. This implies that while citizenship is in one sense a membership status that entails a package of rights, duties, and obligations as well as equality, justice, and autonomy, its development and nature can only be understood through a careful consideration and analysis of contextually specific social conditions. PMID- 25132488 TI - Characterization of overt and occult hepatitis B virus infection among HTLV-1 positive healthy carriers in the Northeast of Iran; AN HTLV-I endemic area. AB - To date, no studies have provided data on hepatitis B virus (HBV) prevalence among asymptomatic, healthy human T-lymphotropic virus (HTLV-I) positive carriers. This sero- and molecular epidemiology study was performed on patients in the Northeast of Iran, which is an endemic area for HTLV-I infection. A total of 109 sera were collected from HTLV-I positive healthy carriers who were admitted to Ghaem Hospital, Mashhad City. All were tested for HBV serology and subsequently, real time PCR was carried out on the samples, regardless of the results of the serology. Standard PCR and direct sequencing were applied on positive samples. All cases were negative for HBsAg, Anti-HBc, and anti-HBs were positive in 34 (31.1%), and 35 (32%) individuals, respectively. There were 19 (17.4%) cases that were positive only for anti-HBs, and they had already received HBV vaccine. 16 (15%) were positive for both anti-HBs and anti-HBc, indicating a past-resolved HBV infection. 18 (16.5%) were isolated as anti-HBc, and 56 (51.3%) were negative for all HBV serological markers. Only one subject (0.9%) had detectable HBV DNA (2153 copy/ml), and assigned as being an occult HBV infection. The low prevalence of HBsAg, despite the high percentage of anti-HBc positive cases, might be related to the suppression effect of HTLV-I on surface protein expression. The low prevalence of HBV infection among HTLV-I positive healthy carriers from an endemic region, indicates that the epidemiology of HTLV-I and HBV coinfection is related to the endemicity of HBV in that region, rather than HTLV-I endemicity. PMID- 25132489 TI - Identification and functional characterization of a sulfate transporter induced by both sulfur starvation and mycorrhiza formation in Lotus japonicus. AB - Arbuscular mycorrhizas (AMs) are one of the most widespread symbioses in the world. They allow plants to receive mineral nutrients from the symbiotic fungus which in turn gets back up to 20% of plant carbon and completes its life cycle. Especially in low-nutrient conditions, AM fungi are capable of significantly improving plant phosphate and nitrogen acquisition, but fewer data are available about sulfur (S) nutrition. We focused on S metabolism in Lotus japonicus upon mycorrhizal colonization under sulfur starvation or repletion. We investigated both tissue sulfate concentrations and S-related gene expression, at cell-type or whole-organ level. Gene expression and sulfate tissue concentration showed that Rhizophagus irregularis colonization can improve plant S nutritional status under S starvation. A group 1 sulfate transporter, LjSultr1;2, induced by both S starvation and mycorrhiza formation, was identified. Its transcript was localized in arbuscule-containing cells, which was confirmed with a promoter-GUS assay, and its function was verified through phenotyping of TILLING mutants in nonmycorrhizal seedlings. LjSultr1;2 thus appears to encode a key protein involved in plant sulfate uptake. In contrast to phosphate transporters, a single gene, LjSultr1;2, seems to mediate both direct and symbiotic pathways of S uptake in L. japonicus. PMID- 25132490 TI - Time since onset of walking predicts tibial bone strength in early childhood. AB - Bone strength in adulthood is known to be affected by health at birth and early childhood. Habitual bone loading is a primary determinant of bone strength in later childhood and adulthood. However, the effects of physical activity in early childhood (e.g. crawling, standing and walking) on bone strength are unknown. Fifty-three children (twenty-seven males) were included in a longitudinal study in their early infancy. Shortly after birth (0.3+/-0.3months), details of mass and height were obtained along with a pQCT scan at 20% distal-proximal tibia length. At 14.8+/-0.5months of age the same data were collected, along with details of age at onset of standing, crawling, supported and unsupported walking. Time since onset of walking unsupported was associated with greater bone mass, cortical bone area, pericortical circumference and polar moment of inertia of both total and cortical bone (all P<0.05). There were no significant associations between other physical activity timepoints and bone measures. Age at onset of walking was not significantly related to mass, length or bone measures at birth. The results suggest that time since attainment of independent walking - representing exposure of the tibia to the large reaction and muscular forces associated with locomotion - is a primary determinant of bone strength in early childhood. This finding raises the possible opportunity of physical activity interventions at young age in paediatric populations associated with low childhood bone strength and late walking (e.g. low birth weight, cerebral palsy and Down's Syndrome, etc.). PMID- 25132492 TI - An in vitro biomechanical comparison of hydroxyapatite coated and uncoated ao cortical bone screws for a limited contact: dynamic compression plate fixation of osteotomized equine 3rd metacarpal bones. AB - OBJECTIVES: To compare the monotonic biomechanical properties of a broad 4.5 mm limited contact-dynamic compression plate (LC-DCP) fixation secured with hydroxyapatite (HA) coated cortical bone screws (HA-LC-DCP) versus uncoated cortical bone screws (AO-LC-DCP) to repair osteotomized equine 3rd metacarpal (MC3) bones. STUDY DESIGN: Experimental. SAMPLE POPULATION: Adult equine cadaveric MC3 bones (n = 12 pair). METHODS: Twelve pairs of equine MC3 were divided into 3 test groups (4 pairs each) for: (1) 4 point bending single cycle to failure testing; (2) 4 point bending cyclic fatigue testing; and (3) torsional single cycle to failure testing. For the HA-LC-DCP-MC3 construct, an 8-hole broad LC-DCP (Synthes Ltd, Paoli, PA) was secured on the dorsal surface of each randomly selected MC3 bone with a combination of four 5.5 mm and four 4.5 mm HA coated cortical screws. For the AO-LC-DCP-MC3 construct, an 8-hole 4.5 mm broad LC-DCP was secured on the dorsal surface of the contralateral MC3 bone with a combination of four 5.5 mm and four 4.5 mm uncoated cortical screws. All MC3 bones had mid-diaphyseal osteotomies. Mean test variable values for each method were compared using a paired t-test within each group. Significance was set at P < .05. RESULTS: Mean yield load, yield bending moment, composite rigidity, failure load, and failure bending moment, under 4 point bending, single cycle to failure, of the HA-LC-DCP fixation were significantly greater than those of the AO-LC-DCP fixation. Mean +/- SD values for the HA-LC-DCP and the AO-LC-DCP fixation techniques, respectively, in single cycle to failure under 4 point bending were: yield load, 26.7 +/- 2.15 and 16.3 +/- 1.38 kN; yield bending moment, 527.4 +/- 42.4 and 322.9 +/- 27.2 N-m; composite rigidity, 5306 +/- 399 and 3003 +/- 300 N-m/rad; failure load, 40.6 +/- 3.94 and 26.5 +/- 2.52 kN; and failure bending moment, 801.9 +/- 77.9 and 522.9 +/- 52.2 N-m. Mean cycles to failure in 4 point bending of the HA-LC-DCP fixation (116,274 +/- 13,211) was significantly greater than that of the AO-LC-DCP fixation 47,619 +/- 6580. Mean yield load, mean composite rigidity, and mean failure load under torsional testing, single cycle to failure was significantly greater for the broad HA-LC DCP fixation compared with the AO-LC-DCP fixation. In single cycle to failure under torsion, mean +/- SD values for the HA-LC-DCP and the AO-LC-DCP fixation techniques, respectively, were: yield load, 101.3 +/- 14.68 and 70.54 +/- 10.20 N m; composite rigidity, 437.9 +/- 32.9 and 220.7 +/- 17.6 N-m/rad; and failure load: 105.7 +/- 15.5 and 75.28 +/- 10.1 N-m. CONCLUSION: HA-LC-DCP was superior to AO-LC-DCP in resisting the static overload forces (palmarodorsal 4 point bending and torsional) and in resisting cyclic fatigue under palmarodorsal 4 point bending. PMID- 25132493 TI - Graphene on mica - intercalated water trapped for life. AB - In this work we study the effect of thermal processing of exfoliated graphene on mica with respect to changes in graphene morphology and surface potential. Mild annealing to temperatures of about 200 degrees C leads to the removal of small amounts of intercalated water at graphene edges. By heating to 600 degrees C the areas without intercalated water are substantially increased enabling a quantification of the charge transfer properties of the water layer by locally resolved Kelvin probe force microscopy data. A complete removal on a global scale cannot be achieved because mica begins to decompose at temperatures above 600 degrees C. By correlating Kelvin probe force microscopy and Raman spectroscopy maps we find a transition from p-type to n-type doping of graphene during thermal processing which is driven by the dehydration of the mica substrate and an accumulation of defects in the graphene sheet. PMID- 25132494 TI - Optimization of ultrasound-assisted extraction of polyphenols from spruce wood bark. AB - Here we describe the ultrasound-assisted extraction of the phenolic compounds from spruce wood bark and present a straight-forward experimental planning method, allowing the optimisation of the process. The effect of ethanol concentration, temperature and extraction time were evaluated through a 3(2).2 experimental planning. The efficiency of the extraction process was appreciated based on factorial ANOVA results. The maximum extraction yield of total polyphenols (13.232mg gallic acid equivalents (GAE)/g of spruce bark tested) was obtained using a process time of 60min, an extraction temperature of 54 degrees C and a concentration of ethanol of 70% respectively. These results indicate that an important quantity of bioactive compounds can be extracted from spruce wood bark by ultrasound assisted extraction technology. PMID- 25132495 TI - Decolorization of azo dye Orange G by aluminum powder enhanced by ultrasonic irradiation. AB - In this work, the decolorization of azo dye Orange G (OG) in aqueous solution by aluminum powder enhanced by ultrasonic irradiation (AlP-UI) was investigated. The effects of various operating operational parameters such as the initial pH, initial OG concentration, AlP dosage, ultrasound power and added hydrogen peroxide (H2O2) concentration were studied. The results showed that the decolorization rate was enhanced when the aqueous OG was irradiated simultaneously by ultrasound in the AlP-acid systems. The decolorization rate decreased with the increase of both initial pH values of 2.0-4.0 and OG initial concentrations of 10-80mg/L, increased with the ultrasound power enhancing from 500 to 900W. An optimum value was reached at 2.0g/L of the AlP dosage in the range of 0.5-2.5g/L. The decolorization rate enhanced significantly by the addition of hydrogen peroxide in the range of 10-100mM to AlP-UI system reached an optimum value of 0.1491min(-1). The decolorization of OG appears to involve primarily oxidative steps, the cleavage of NN bond, which were verificated by the intermediate products of OG under the optimal tested degradation system, aniline and 1-amino-2-naphthol-6,8-disulfonate detected by the LC-MS. PMID- 25132496 TI - ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. AB - Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of viral hepatitis, insulin resistance, hepatosteatosis, and nonalcoholic steatohepatitis (NASH), disorders that increase risk of hepatocellular carcinoma (HCC). To determine whether and how ER stress contributes to obesity-driven hepatic tumorigenesis we fed wild-type (WT) and MUP-uPA mice, in which hepatocyte ER stress is induced by plasminogen activator expression, with high-fat diet. Although both strains were equally insulin resistant, the MUP-uPA mice exhibited more liver damage, more immune infiltration, and increased lipogenesis and, as a result, displayed classical NASH signs and developed typical steatohepatitic HCC. Both NASH and HCC development were dependent on TNF produced by inflammatory macrophages that accumulate in the MUP-uPA liver in response to hepatocyte ER stress. PMID- 25132498 TI - Stem cell therapy for glaucoma: science or snake oil? AB - In recent years there has been substantial progress in developing stem cell treatments for glaucoma. As a downstream approach that targets the underlying susceptibility of retinal ganglion and trabecular meshwork cells, stem cell therapy has the potential to both replace lost, and protect damaged, cells by secreting neurotrophic factors. A variety of sources, including embryonic cells, adult cells derived from the central nervous system, and induced pluripotent stem cells show promise as therapeutic approaches. Even though safety concerns and ethical controversies have limited clinical implementation, some institutions have already commercialized stem cell therapy and are using direct-to-consumer advertising to attract patients with glaucoma. We review the progress of stem cell therapy and its current commercial availability. PMID- 25132499 TI - To What did They Consent? Understanding Consent Among Low Literacy Participants in a Microbicide Feasibility Study in Mazabuka, Zambia. AB - We conducted a study to review the consenting process in a vaginal microbicide feasibility study conducted in Mazabuka, Zambia. Participants were drawn from those participating in the microbicide study. A questionnaire and focus group discussion were used to collect information on participants' understanding of study aims, risks and benefits. Altogether, 200 participants took part in this study. The results of the study showed that while all participants signed or endorsed their thumbprints to the consent forms, full informed consent was not attained from most of the participants since 77% (n = 154) of the participants had numerous questions about the study and 34% (n = 68) did not know who to get in touch with concerning the study. Study objectives were not fully understood by over 61% of the participants. Sixty four percent of the participants were not sure of the risks of taking part in the microbicide study. A significant number thought the study was all about determining their HIV status. Some participants were concerned that their partners were not on the trial as they were convinced that being on the study meant that that they had a lifetime protection from HIV infection. The process of obtaining consent was inadequate as various phases of the study were not fully understood. We recommend the need for researchers to reinforce the consenting process in all studies and more so when studies are conducted in low literacy populations. PMID- 25132497 TI - BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. AB - Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive (Ph(+)) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However, emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib resistance. We found that clinically reported BCR-ABL1 compound mutants center on 12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib, ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer high-level resistance to TKIs, including ponatinib. In vitro resistance profiling was predictive of treatment outcomes in Ph(+) leukemia patients. Structural explanations for compound mutation-based resistance were obtained through molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound mutants confer different levels of TKI resistance, necessitating rational treatment selection to optimize clinical outcome. PMID- 25132502 TI - Genetic targeting of microglia. AB - Genetic targeting of microglia and other myeloid cells in the central nervous system (CNS) is highly desirable as they are critical effectors and regulators of changes in CNS homeostasis during development as well as in health and disease. Therefore, genetic reprogramming of microglia could constitute a central approach for potentially reducing disease burden. Previous attempts to target only microglia in vivo failed because of the similarities to their hematopoietic relatives in the circulation. However, this concept has been challenged by recent results of developmental and gene expression profiling studies which used novel molecular biological tools to unravel the origin of microglia and to define their role as specialized tissue macrophages clearly distinct from monocytes or monocyte-derived macrophages. The aim of this review is to recapitulate the history of microglia targeting approaches and finally highlight recent achievements in the field. We will discuss the pros and cons of the newly available genetic tools, their potential for future microglia research and genetic strategies. PMID- 25132500 TI - Impaired hypercarbic and hypoxic responses from developmental loss of cerebellar Purkinje neurons: implications for sudden infant death syndrome. AB - Impaired responsivity to hypercapnia or hypoxia is commonly considered a mechanism of failure in sudden infant death syndrome (SIDS). The search for deficient brain structures mediating flawed chemosensitivity typically focuses on medullary regions; however, a network that includes Purkinje cells of the cerebellar cortex and its associated cerebellar nuclei also helps mediate responses to carbon dioxide (CO2) and oxygen (O2) challenges and assists integration of cardiovascular and respiratory interactions. Although cerebellar nuclei contributions to chemoreceptor challenges in adult models are well described, Purkinje cell roles in developing models are unclear. We used a model of developmental cerebellar Purkinje cell loss to determine if such loss influenced compensatory ventilatory responses to hypercapnic and hypoxic challenges. Twenty-four Lurcher mutant mice and wild-type controls were sequentially exposed to 2% increases in CO2 (0-8%) or 2% reductions in O2 (21 13%) over 4 min, with return to room air (21% O2/79% N2/0% CO2) between each exposure. Whole body plethysmography was used to continuously monitor tidal volume (TV) and breath frequency (f). Increased f to hypercapnia was significantly lower in mutants, slower to initiate, and markedly lower in compensatory periods, except for very high (8%) CO2 levels. The magnitude of TV changes to increasing CO2 appeared smaller in mutants but only approached significance. Smaller but significant differences emerged in response to hypoxia, with mutants showing smaller TV when initially exposed to reduced O2 and lower f following exposure to 17% O2. Since cerebellar neuropathology appears in SIDS victims, developmental cerebellar neuropathology may contribute to SIDS vulnerability. PMID- 25132501 TI - Markers of angiogenesis associated with surgical attenuation of congenital portosystemic shunts in dogs. AB - BACKGROUND: Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the intrahepatic portal veins. Surgical CPSS attenuation results in the development of the intrahepatic portal vasculature, the precise mechanism for which is unknown, although new vessel formation by angiogenesis is suspected. HYPOTHESIS: That the degree of portal vascular development and the increase in portal vascularization after CPSS attenuation is significantly associated with hepatic vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) gene expression and serum VEGF concentration. ANIMALS: Client-owned dogs with CPSS undergoing surgical treatment. Forty-nine dogs were included in the gene expression data and 35 in the serum VEGF data. MATERIALS AND METHODS: Dogs surgically treated by partial or complete CPSS attenuation were prospectively recruited. Relative gene expression of VEGF and VEGFR2 was measured in liver biopsy samples taken at initial and follow-up surgery using quantitative polymerase chain reaction. Serum VEGF concentration was measured before and after CPSS attenuation using a canine specific ELISA. Statistical significance was set at the 5% level (P <= .05). RESULTS: There was a significant increase in the mRNA expression of VEGFR2 after partial attenuation (P = .006). Dogs that could tolerate complete attenuation had significantly greater VEGFR2 mRNA expression than those that only tolerated partial attenuation (P = .037). Serum VEGF concentration was significantly increased at 24 (P < .001) and 48 (P = .003) hours after attenuation. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest that intrahepatic angiogenesis is likely to occur after the surgical attenuation of CPSS in dogs, and contributes to the development of the intrahepatic vasculature postoperatively. PMID- 25132503 TI - Reduced beta-cell reserve and pancreatic volume in survivors of childhood acute lymphoblastic leukaemia treated with bone marrow transplantation and total body irradiation. AB - BACKGROUND: Impaired glucose tolerance (IGT) and diabetes mellitus (DM) occur more frequently after bone marrow transplantation and total body irradiation (BMT/TBI), but the mechanism is unclear. This study investigates insulin sensitivity, beta-cell reserve and pancreatic volume in adult survivors of childhood acute lymphoblastic leukaemia (ALL). METHOD: Survivors (aged 16-26 years) of ALL treated with BMT/TBI (10-14.4 Gy) Group 1 (n = 20, 10 m) were compared with a chemotherapy-only Group 2 (n = 28, 11 m). Participants underwent assessments of insulin sensitivity by whole body composite-insulin-sensitivity index (ISIcomp ) from oral glucose tolerance tests (OGTTs); first (AIRarg , AIRg , AUCin10 ) and second (AUC in second phase ) phase insulin responses from arginine-intravenous glucose tolerance tests; and pancreatic volume by abdominal magnetic resonance imaging (MRI). Data were analysed by odds ratio, Chi-square or Fisher's exact tests, Student's t-tests, analysis of covariance (ancova) and Pearson's or partial correlations (5% significance). RESULTS: Abnormal OGTTs were documented in Group 1 (DM = 2, IGT = 7). Insulin secretion adjusted for insulin sensitivity was lower in Group 1 than Group 2 as a whole [LogAIRarg (P = 0.008), logAIRg (P = 0.013) and logAUCin10 (P = 0.014)] and after exclusion of those with abnormal glucose tolerance [logAIRarg (P = 0.011), logAIRg (P = 0.007) and logAUCin10 (P = 0.006)]. Group 1 had lower pancreatic volume than Group 2 [52.0 (14.2) vs 72.8 (23.5), P = 0.001] cm(3) , and results were consistent after adjustment for size by body surface area (P = 0.019). Pancreatic volume correlated with logAIRarg adjusted log ISIcomp (partial correlation = 0.34, P = 0.025). CONCLUSIONS: Adult survivors of childhood BMT/TBI for ALL demonstrated reduced beta-cell reserve and smaller pancreatic volume, both likely additional aetiological factors, with reduced insulin sensitivity, in their increased risk of diabetes. PMID- 25132504 TI - Gas in the retropharyngeal space: descending necrotising mediastinitis. PMID- 25132505 TI - Israel-Gaza conflict. PMID- 25132506 TI - Chikungunya virus control: is a vaccine on the horizon? PMID- 25132508 TI - Utilizing intraspecific variation in phenotypic plasticity to bolster agricultural and forest productivity under climate change. AB - Climate change threatens the ability of agriculture and forestry to meet growing global demands for food, fibre and wood products. Information gathered from genotype-by-environment interactions (G * E), which demonstrate intraspecific variation in phenotypic plasticity (the ability of a genotype to alter its phenotype in response to environmental change), may prove important for bolstering agricultural and forest productivity under climate change. Nonetheless, very few studies have explicitly quantified genotype plasticity productivity relationships in agriculture or forestry. Here, we conceptualize the importance of intraspecific variation in agricultural and forest species plasticity, and discuss the physiological and genetic factors contributing to intraspecific variation in phenotypic plasticity. Our discussion highlights the need for an integrated understanding of the mechanisms of G * E, more extensive assessments of genotypic responses to climate change under field conditions, and explicit testing of genotype plasticity-productivity relationships. Ultimately, further investigation of intraspecific variation in phenotypic plasticity in agriculture and forestry may prove important for identifying genotypes capable of increasing or sustaining productivity under more extreme climatic conditions. PMID- 25132507 TI - Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial. AB - BACKGROUND: Chikungunya virus--a mosquito-borne alphavirus--is endemic in Africa and south and southeast Asia and has recently emerged in the Caribbean. No drugs or vaccines are available for treatment or prevention. We aimed to assess the safety, tolerability, and immunogenicity of a new candidate vaccine. METHODS: VRC 311 was a phase 1, dose-escalation, open-label clinical trial of a virus-like particle (VLP) chikungunya virus vaccine, VRC-CHKVLP059-00-VP, in healthy adults aged 18-50 years who were enrolled at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Participants were assigned to sequential dose level groups to receive vaccinations at 10 MUg, 20 MUg, or 40 MUg on weeks 0, 4, and 20, with follow-up for 44 weeks after enrolment. The primary endpoints were safety and tolerability of the vaccine. Secondary endpoints were chikungunya virus-specific immune responses assessed by ELISA and neutralising antibody assays. This trial is registered with ClinicalTrials.gov, NCT01489358. FINDINGS: 25 participants were enrolled from Dec 12, 2011, to March 22, 2012, into the three dosage groups: 10 MUg (n=5), 20 MUg (n=10), and 40 MUg (n=10). The protocol was completed by all five participants at the 10 MUg dose, all ten participants at the 20 MUg dose, and eight of ten participants at the 40 MUg dose; non completions were for personal circumstances unrelated to adverse events. 73 vaccinations were administered. All injections were well tolerated, with no serious adverse events reported. Neutralising antibodies were detected in all dose groups after the second vaccination (geometric mean titres of the half maximum inhibitory concentration: 2688 in the 10 MUg group, 1775 in the 20 MUg group, and 7246 in the 40 MUg group), and a significant boost occurred after the third vaccination in all dose groups (10 MUg group p=0.0197, 20 MUg group p<0.0001, and 40 MUg group p<0.0001). 4 weeks after the third vaccination, the geometric mean titres of the half maximum inhibitory concentration were 8745 for the 10 MUg group, 4525 for the 20 MUg group, and 5390 for the 40 MUg group. INTERPRETATION: The chikungunya VLP vaccine was immunogenic, safe, and well tolerated. This study represents an important step in vaccine development to combat this rapidly emerging pathogen. Further studies should be done in a larger number of participants and in more diverse populations. FUNDING: Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, and National Institutes of Health. PMID- 25132509 TI - Production of D-lactic acid in a continuous membrane integrated fermentation reactor by genetically modified Saccharomyces cerevisiae: enhancement in D-lactic acid carbon yield. AB - Poly d-lactic acid is an important polymer because it improves the thermostability of poly l-lactic acid by stereo complex formation. To demonstrate potency of continuous fermentation using a membrane-integrated fermentation reactor (MFR) system, continuous fermentation using genetically modified Saccharomyces cerevisiae which produces d-lactic acid was performed at the low pH and microaerobic conditions. d-Lactic acid continuous fermentation using the MFR system by genetically modified yeast increased production rate by 11-fold compared with batch fermentation. In addition, the carbon yield of d-lactic acid in continuous fermentation was improved to 74.6 +/- 2.3% compared to 39.0 +/- 1.7% with batch fermentation. This dramatic improvement in carbon yield could not be explained by a reduction in carbon consumption to form cells compared to batch fermentation. Further detailed analysis at batch fermentation revealed that the carbon yield increased to 76.8% at late stationary phase. S. cerevisiae, which exhibits the Crabtree-positive effect, demonstrated significant changes in metabolic activities at low sugar concentrations (Rossignol et al., Yeast, 20, 1369-1385, 2003). Moreover, lactate-producing S. cerevisiae requires ATP supplied not only from the glycolytic pathway but also from the TCA cycle (van Maris et al., Appl. Environ. Microbiol., 70, 2898-2905, 2004). Our finding was revealed that continuous fermentation, which can maintain the conditions of both a low sugar concentration and air supply, results in Crabtree-positive and lactate producing S. cerevisiae for suitable conditions of d-lactic acid production with respect to redox balance and ATP generation because of releasing the yeast from the Crabtree effect. PMID- 25132510 TI - [Premature constriction of the ductus arteriosus]. PMID- 25132511 TI - [Therapeutic approach to paediatric septic arthritis: are we too aggressive?]. PMID- 25132513 TI - 17beta-Estradiol administration promotes delayed cutaneous wound healing in 40 week ovariectomised female mice. AB - This study investigated the effect of 17beta-estradiol on wound healing in 40 week ovariectomised female mice. Thirty-six-week-old female mice were divided into three groups: medication with 17beta-estradiol after ovariectomy (OVX + 17beta-estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full thickness wounds, and the OVX + 17beta-estradiol group was administered 17beta estradiol at 0.01 g/day until healing. In the OVX + 17beta-estradiol group, the ratio of wound area was significantly smaller than those of the OVX and SHAM groups on days 1-3, 5, 6, 8-12 and 9-12, respectively, the numbers of neutrophils and macrophages were significantly smaller than those on days 3 and 7, the ratio of re-epithelialisation was significantly higher than those on days 3 and 11, the ratio of myofibroblasts was significantly higher than those on day 11 and smaller on day 14, and the ratio of collagen fibres was significantly larger than that of the OVX group on days 7-14. We found that 17beta-estradiol administration promotes cutaneous wound healing in 40-week female mice by reducing wound area, shortening inflammatory response, and promoting re-epithelialisation, collagen deposition and wound contraction. Our results suggest that cutaneous wound healing that is delayed because of ageing is promoted by exogenous and continuous 17beta-estradiol administration. PMID- 25132514 TI - Oxidative damage in diabetics: insights from a graduate study in La Reunion University. AB - Due to the growing incidence of diabetes in developed nations, there is a compelling case to be made for teaching graduate students more deeply about mechanisms underlying this disease. Diabetes is associated with enhanced oxidative stress and protein glycation via the covalent binding of glucose molecules. Albumin represents the major plasmatic protein and undergoes enhanced glycoxidative modifications in diabetic condition. La Reunion Island, a French department located in the Indian Ocean exhibit a growing incidence of diabetes. At the University of La Reunion, our research group named GEICO (Groupe d'Etude sur l'Inflammation Chronique et l'Obesite) participated to foster research and training in diabetes context and focuses on the impact of glycated albumin mediated oxidative stress on cell physiopathology. A laboratory course was designed by our group to introduce graduate students to cutting edge techniques in redox biology while providing insights into scientific processes and methods. This two weeks research laboratory training took place at CYROI, a local biotechnology center that provides advanced facilities for research, business, and education. Using histochemistry, molecular biology, biochemical techniques, student investigated oxidative damages in liver from leptin receptor deficient diabetic mice compared to control littermates. In addition, they used an in vitro model by assaying oxidative impact of glycated albumin on hepatoma carcinoma HepG2 cells. This article gives an overview of the organization and protocol used by the students during their two weeks training in the laboratory. Therefore, it may be helpful for teaching graduate students techniques used in research laboratory working on redox biology. PMID- 25132512 TI - Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are predictors of bronchiolitis severity. AB - BACKGROUND: Bronchiolitis is the leading cause of hospitalization in infants. Biomarkers of disease severity might help in clinical management. OBJECTIVE: To determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW caspase 3/7 ratio in bronchiolitis. METHODS: Previously healthy children less than 24 months of age with bronchiolitis were recruited from the Texas Children's emergency room and intensive care unit from October 2010 to April 2011. Demographic, clinical information, and NW samples were obtained at enrollment. NW samples were analyzed for respiratory viruses, caspase 3/7, and LDH. RESULTS: A viral pathogen was detected in 91.6% of 131 children, with the most common being respiratory syncytial virus and human rhinovirus. A single infection was found in 61.8% of subjects and co-infection in 29.8%. Children admitted to ICU had significantly higher NW-LDH than children sent home from the ER or admitted to the general floor (P = 0.02). Children infected with RSV had the highest NW-LDH concentration (P = 0.03) compared with other viral infections. NW-LDH and NW caspase were significantly correlated (r = 0.77, P < 0.0001). The univariate models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated with hospitalization. Mutivariate regression analyses suggested a complex interaction between the biomarkers, demographics, and disposition. CONCLUSIONS: NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions with demographic factors are predictive of bronchiolitis severity and can help distinguish children requiring ICU-level care from those admitted to the general floor, or discharged home from the emergency center. PMID- 25132515 TI - Magnetic ring anastomosis of suprahepatic vena cava: novel technique for liver transplantation in rat. AB - To improve the technique of suprahepatic vena cava (SHVC) reconstruction in rat OLT, novel magnetic rings were designed and manufactured to facilitate reconstruction of SHVC and shorten the anhepatic time. One-hundred and twenty adult male Wistar rats were randomly divided into two groups: rings group (n = 30), using magnetic rings for SHVC reconstruction; suture group (n = 30), 7/0 prolene suture was used for SHVC running anastomosis as control. Cuff techniques were used for portal vein and infrahepatic vena cava reconstruction as Kamada and Calne described. The bile duct was reconnected with a stent. The hepatic re arterialization was omitted. In the rings group, the SHVC reconstruction took 0.91 +/- 0.24 (mean +/- SD) min; the anhepatic phase and the recipient operation time were 5.63 +/- 0.65 min and 36.02 +/- 8.02 min, respectively. In suture group, the anastomotic time of SHVC was 10.40 +/- 2.11 min; the anhepatic phase and the recipient operation time were 17.76 +/- 2.51 and 49.38 +/- 12.06 min, respectively, and there was statistically significant difference between the two groups. The ALT levels reached peak at 24 h post-OLT (186.2 +/- 32.5 IU/l) and restored to normal level at 96 h gradually. In the rings group, 29 of 30 rats survived at day 7 and 28 of 30 rats survived at day 30. In contrast, only 25 of 30 recipients in suture group remained alive at day 7 and 22 of 30 remained alive at day 30 (P < 0.05). Better anastomotic healing was founded in rings group by pathology and scanning electron microscope. The magnetic rings technique provides a novel, simple method for SHVC reconstruction of OLT in rat. It significantly shortens anhepatic phase, while the success rate of the operation is satisfactory. PMID- 25132516 TI - A randomised controlled trial of PEGASUS, a psychoeducational programme for young people with high-functioning autism spectrum disorder. AB - BACKGROUND: Psychoeducation is an essential component of postdiagnostic care for people with ASD (autism spectrum disorder), but there is currently no evidence base for clinical practice. We designed, manualised and evaluated PEGASUS (psychoeducation group for autism spectrum understanding and support), a group psychoeducational programme aiming to enhance the self-awareness of young people with ASD by teaching them about their diagnosis. METHODS: This single-blind RCT (randomised control trial) involved 48 young people (9-14 years) with high functioning ASD. Half were randomly assigned to PEGASUS, administered in six weekly group sessions, with the others receiving no additional intervention. ASD related self-awareness, the primary outcome, was evaluated using the bespoke Autism Knowledge Quiz (AKQ). Secondary outcome measures included the Rosenberg Self-Esteem Scale. All measures were collected during home visits and scored by researchers blind to group assignment. The trial is registered on ClinicalTrials (NCT01187940, http://www.clinicaltrials.gov) and was funded by the Baily Thomas Charitable Trust. RESULTS: Bootstrap multiple regression showed ASD knowledge (beta = .29, p < .001, 95% CIs [0.13, 0.44]) and ASD self-awareness (beta = .42, p = .001, 95% CIs [0.17, 0.67]), measured by number of ASD-related personal strengths and difficulties listed by participants, increased for those who attended PEGASUS (n = 24) compared with controls (n = 24). There was no effect of PEGASUS on self-esteem by self-report (beta = .10, p = .404, 95% CIs [-0.14, 0.35]) or parent report (beta = .12, p = .324, 95% CIs [-0.12, 0.36]). CONCLUSIONS: After PEGASUS, participants had more general knowledge about ASD, and showed a greater awareness of their collection of unique strengths and difficulties associated with ASD. Psychoeducation did not lower self-esteem. This RCT provides initial evidence for PEGASUS's efficacy as a psychoeducation programme for people with ASD. PMID- 25132517 TI - Advances in classification, basic mechanisms and clinical science in ankylosing spondylitis and axial spondyloarthritis. AB - The field of spondyloarthritis (SpA) has seen huge advances over the past 5 years. The classification of axial disease has been redefined by the axial SpA criteria that incorporate disease captured before radiographic damage is evident as well as established erosive sacroiliac joint disease. Our knowledge of genetics and basic immunological pathways has progressed significantly. In addition, revolutionary progress has been achieved with the availability of tumour necrosis factor inhibitors for treating patients with moderate to severe disease. In parallel, several of novel biomarkers have been identified that show significant promise for the future. Advances in magnetic resonance imaging have helped define positive disease. We have identified that T1 and short tau inversion recovery sequences are best for the diagnosis of axial SpA, and gadolinium contrast is not additive for diagnosis. Progress has been made in identifying potential agents and strategies that reduce radiographic progression. Several referral strategies aimed at appropriate identification of patients have been trialled and found to be effective. There is still substantial work ahead, but the advances of the last 5 years have made a huge and tangible difference at the clinical coalface, and we suggest that this trend will continue. PMID- 25132518 TI - Altered manifestations of skin disease at sites affected by neurological deficit. AB - BACKGROUND: The contribution of the nervous system to inflammation in general and inflammatory skin disease in particular has been underappreciated. It is now apparent that an intact neural component is required for the conventional clinical manifestations of many inflammatory skin diseases. OBJECTIVES: To investigate the relationship between nerve damage and skin disease. METHODS: Previous individual reports since 1966 were collected systematically and the clinical observations described therein were placed within current concepts of neurogenic inflammation. RESULTS: We reviewed the literature and identified 23 cases of alterations in the appearance or distribution of skin disorders in patients with acquired central or peripheral neural damage or dysfunction. In 19 cases, near or complete resolution of pre-existing skin lesions occurred in areas directly or indirectly supplied by a subsequently injured nervous system. Exacerbation or new onset of skin lesions occurred in only four cases. The neural deficits described included damage within the peripheral or central nervous system resulting in pure sensory, pure motor or combined sensory and motor deficits. CONCLUSIONS: These cases highlight the importance of neural innervation and neurogenic inflammation in the development of inflammatory skin disease and prompt further examination of the use of neural blockade as an adjunctive therapy in the treatment of inflammatory dermatoses. PMID- 25132519 TI - Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia. AB - Acute myeloid leukemia (AML) patients aged >= 60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m(2)/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20-30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m(2)/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13 724 days). Grade 3-4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1-2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m(2)/day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML. PMID- 25132520 TI - A pilot validation of multi-echo based echo-planar correlated spectroscopic imaging in human calf muscles. AB - A current limitation of MR spectroscopic imaging of multiple skeletal muscles is prolonged scan duration. A significant reduction in the total scan duration using the echo-planar correlated spectroscopic imaging (EP-COSI) sequence was accomplished using two bipolar readout trains with different phase-encoded echoes for one of two spatial dimensions within a single repetition time (TR). The second bipolar readout was used for spatially encoding the outer k-space, whereas the first readout was used for the central k-space only. The performance of this novel sequence, called multi-echo based echo-planar correlated spectroscopic imaging (ME-EPCOSI), was demonstrated by localizing specific key features in calf muscles and bone marrow of 11 healthy volunteers and five subjects with type 2 diabetes (T2D). A 3 T MRI-MRS scanner equipped with a transmit-receive extremity coil was used. Localization of the ME-EPCOSI sequence was in good agreement with the earlier single-readout based EP-COSI sequence and the required scan time was reduced by a factor of two. In agreement with an earlier report using single voxel based 2D MRS, significantly increased unsaturated pools of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) and decreased IMCL and EMCL unsaturation indices (UIs) were observed in the soleus and tibialis anterior muscle regions of subjects with T2D compared with healthy controls. In addition, significantly decreased choline content was observed in the soleus of T2D subjects compared with healthy controls. Multi-voxel characterization of IMCL and EMCL ratios and UI in the calf muscle may be useful for the non-invasive assessment of altered lipid metabolism in the pathophysiology of T2D. PMID- 25132521 TI - Prevalence of postpartum infections: a population-based observational study. AB - We investigated the prevalence of postpartum infections among women giving birth during 1 year in a population-based observational/questionnaire study at seven hospitals in the southeast region of Sweden. Of the women >99% (n = 11,124) received a questionnaire to inquire if they had endometritis, mastitis, or wound, urinary tract or any other infection within 2 months postpartum and whether they received antibiotics for this. Prevalence rates for infections and antibiotic treatment were estimated. The response rate was 60.1%. At least one infectious episode was reported by 10.3% of the women and 7.5% had received antibiotics. The prevalence for infections with and without antibiotics were, respectively, mastitis 4.7% and 2.9%, urinary tract infection 3.0% and 2.4%, endometritis 2.0% and 1.7%, wound infection 1.8% and 1.2%. There was no inter-county difference in infection prevalence. Clinical postpartum infections in a high-resource setting are relatively common. PMID- 25132523 TI - Bias induced transition from an ohmic to a non-ohmic interface in supramolecular tunneling junctions with Ga2O3/EGaIn top electrodes. AB - This study describes that the current rectification ratio, R = |J|(-2.0 V)/|J|(+2.0 V) for supramolecular tunneling junctions with a top-electrode of eutectic gallium indium (EGaIn) that contains a conductive thin (0.7 nm) supporting outer oxide layer (Ga2O3), increases by up to four orders of magnitude under an applied bias of >+1.0 V up to +2.5 V; these junctions did not change their electrical characteristics when biased in the voltage range of +/-1.0 V. The increase in R is caused by the presence of water and ions in the supramolecular assemblies which react with the Ga2O3/EGaIn layer and increase the thickness of the Ga2O3 layer. This increase in the oxide thickness from 0.7 nm to ~2.0 nm changed the nature of the monolayer-top-electrode contact from an ohmic to a non-ohmic contact. These results unambiguously expose the experimental conditions that allow for a safe bias window of +/-1.0 V (the range of biases studies of charge transport using this technique are normally conducted) to investigate molecular effects in molecular electronic junctions with Ga2O3/EGaIn top-electrodes where electrochemical reactions are not significant. Our findings also show that the interpretation of data in studies involving applied biases of >1.0 V may be complicated by electrochemical side reactions which can be recognized by changes of the electrical characteristics as a function voltage cycling or in current retention experiments. PMID- 25132522 TI - Ranolazine attenuates mechanical allodynia associated with demyelination injury. AB - OBJECTIVE: The aim of this study was to determine whether ranolazine, a new medication that targets sodium channels to improve cardiac ischemia and angina, could be an effective analgesic agent for pain associated with demyelination injury. BACKGROUND: Many agents have been used to treat neuropathic pain but not all neuropathic conditions respond similarly to treatment. We have demonstrated that ranolazine, an agent that blocks voltage-gated sodium channels Nav 1.4, 1.5, 1.7, and 1.8, is effective in attenuating mechanical hyperalgesia in both complete Freund's adjuvant and spared nerve injury preclinical models of inflammatory and neuropathic pain, respectively. Here we test the efficacy of this drug in a newly validated model of demyelination injury that responds uniquely to a number of treatment options. METHODS: After determination of baseline nerve conduction velocities (NCVs) and withdrawal responses from heat and mechanical stimulation in male Sprague-Dawley rats (300-350 g), 1 MUg/30 MUL of doxorubicin was injected into one sciatic nerve. The contralateral nerve provided a sham-injected control. Two weeks after doxorubicin injection, NCV and sensitivity to heat and mechanical stimulation were reassessed before and after treatment with ranolazine (10, 30, 50 mg/kg) administered intraperitoneally using an experimenter-blinded, randomized design. RESULTS: Doxorubicin injection produced a significant hyperalgesic effect in response to mechanical but not heat stimulation. Conduction velocities in the injected limbs were reduced when compared with controls. Ranolazine reduced mechanical allodynia with peak efficacy at 30 mg/kg. Fifty milligram/kilogram ranolazine restored NCVs by approximately 50%, but had no effect in the uninjected limb. CONCLUSIONS: Ranolazine exerts broad-spectrum actions to reduce mechanical allodynia that is associated with peripheral demyelination injury. PMID- 25132524 TI - Determinants of Gli2 co-activation of wildtype and naturally truncated androgen receptors. AB - BACKGROUND: Gli2, a transcription factor in the Hedgehog pathway, is overexpressed in castrate-resistant prostate cancer (PCa). Previously we showed that Gli2 overexpression increased transcriptional activity of androgen receptor (AR) and conferred androgen growth-independence to normally growth-dependent PCa cells. Here we localized the regions of AR-Gli2 protein interaction and determined the domains within Gli2 needed for AR co-activation. METHODS: Co immunoprecipitation and GST-pulldown assays were used to define AR-Gli binding domains. Co-activation assays using androgen-responsive promoter reporters were used to define Gli2 regions needed for AR co-activation. Chromatin immunoprecipitation (ChIP) assays were used to confirm nuclear interactions of Gli2 with AR in PCa cells. RESULTS: The Gli2 C-terminal domain (CTD) is sufficient for AR co-activation. Two elements within the CTD were required: (1) an AR binding domain within aa628-897; and (2) at least part of the Gli2 transactivation domain within aa1252-1586. In turn, Gli2 binds the tau5/AF5 ligand-independent activation domain in the AR N-terminus. Mutations in the WxxLF motif in tau5/AF5 greatly diminished binding to Gli2-CTD. Gli2 interaction with AR tau5/AF5 was further substantiated by the ability of Gli2/Gli2-CTD to co activate truncated AR splice variants (AR-V7/ARV567es). ChIP assays confirmed that Gli2 associates with chromatin at androgen response elements found near androgen-responsive genes in LNCaP cells. These assays also showed that AR associates with chromatin containing a Gli-response element near a Gli-responsive gene. CONCLUSION: Our findings indicate that Gli2 overexpression in PCa cells might support development of castration resistant PCa through AR co-activation and suggests that AR might modulate transcription from Gli2. PMID- 25132527 TI - Host-derived CD8+ dendritic cells protect against acute graft-versus-host disease after experimental allogeneic bone marrow transplantation. AB - Graft-versus-host disease (GVHD) is a frequent life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT) and induced by donor-derived T cells that become activated by host antigen-presenting cells. To address the relevance of host dendritic cell (DC) populations in this disease, we used mouse strains deficient in CD11c(+) or CD8alpha(+) DC populations in a model of acute GVHD where bone marrow and T cells from BALB/c donors were transplanted into C57BL/6 hosts. Surprisingly, a strong increase in GVHD-related mortality was observed in the absence of CD11c(+) cells. Likewise, Batf3-deficient (Batf3(-/-)) mice that lack CD8alpha(+) DCs also displayed a strongly increased GVHD-related mortality. In the absence of CD8alpha(+) DCs, we detected an increased activation of the remaining DC populations after HSCT, leading to an enhanced priming of allogeneic T cells. Importantly, this was associated with reduced numbers of regulatory T cells and transforming growth factor-beta levels, indicating an aggravated failure of peripheral tolerance mechanisms after HSCT in the absence of CD8alpha(+) DCs. In summary, our results indicate a critical role of CD8alpha(+) DCs as important inducers of regulatory T cell-mediated tolerance to control DC activation and T cell priming in the initiation phase of GVHD. PMID- 25132528 TI - Crime event 3D reconstruction based on incomplete or fragmentary evidence material--case report. AB - Using our own experience in 3D analysis, the authors will demonstrate the possibilities of 3D crime scene and event reconstruction in cases where originally collected material evidence is largely insufficient. The necessity to repeat forensic evaluation is often down to the emergence of new facts in the course of case proceedings. Even in cases when a crime scene and its surroundings have undergone partial or complete transformation, with regard to elements significant to the course of the case, or when the scene was not satisfactorily secured, it is still possible to reconstruct it in a 3D environment based on the originally-collected, even incomplete, material evidence. In particular cases when no image of the crime scene is available, its partial or even full reconstruction is still potentially feasible. Credibility of evidence for such reconstruction can still satisfy the evidence requirements in court. Reconstruction of the missing elements of the crime scene is still possible with the use of information obtained from current publicly available databases. In the study, we demonstrate that these can include Google Maps((r)*), Google Street View((r)*) and available construction and architecture archives. PMID- 25132529 TI - Preterm birth and neonatal mortality in China in 2011. AB - OBJECTIVE: To determine the incidence of preterm birth, its regional distribution, and associated neonatal mortality in mainland China. METHODS: In a multicenter, hospital-based investigation of preterm birth, 2011 data were obtained from the seven administrative regions of mainland China. Between one and three subcenters were randomly selected for each administrative region, followed by secondary and tertiary hospitals within the chosen subcenters. Data were obtained from women's medical records, and obstetric and perinatal events were summarized. RESULTS: Data for 107,905 deliveries were analyzed, which included 7769 (7.1%) preterm births (occurring between 28 and 37 weeks of pregnancy). The incidence varied among regions. Late preterm birth (between 34 and 37 weeks) accounted for 5495 (70.7%) of preterm births. The neonatal mortality rate was 33 deaths per 1000 live preterm births. Of the 254 neonatal deaths, 147 (57.9%) occurred after very preterm birth (between 28 and 32 weeks). Overall, 4519 (58.2%) preterm births occurred by cesarean. CONCLUSION: The distribution of preterm birth across China is unbalanced, and neonatal mortality associated with preterm birth is high. PMID- 25132530 TI - Unilateral microphthalmia or anophthalmia in eight pythons (Pythonidae). AB - OBJECTIVE: To provide morphological descriptions of microphthalmia or anophthalmia in eight pythons using microcomputerized tomography (MUCT), magnetic resonance imaging (MRI), and histopathology. ANIMALS STUDIED: Seven Burmese pythons (Python bivittatus) and one ball python (P. regius) with clinically normal right eyes and an abnormal or missing left eye. PROCEDURE: At the time of euthanasia, four of the eight snakes underwent necropsy. Hereafter, the heads of two Burmese pythons and one ball python were examined using MUCT, and another Burmese python was subjected to MRI. Following these procedures, the heads of these four pythons along with the heads of an additional three Burmese pythons were prepared for histology. RESULTS: All eight snakes had left ocular openings seen as dermal invaginations between 0.2 and 2.0 mm in diameter. They also had varying degrees of malformations of the orbital bones and a limited presence of nervous, glandular, and muscle tissue in the posterior orbit. Two individuals had small but identifiable eyes. Furthermore, remnants of the pigmented embryonic framework of the hyaloid vessels were found in the anophthalmic snakes. Necropsies revealed no other macroscopic anomalies. CONCLUSIONS: Eight pythons with unilateral left-sided microphthalmia or anophthalmia had one normal eye and a left orbit with malformed or incompletely developed ocular structures along with remnants of fetal structures. These cases lend further information to a condition that is often seen in snakes, but infrequently described. PMID- 25132531 TI - The influence of hydrogen bonding on the nonlinear optical properties of a semiorganic material NH4B[D-(+)-C4H4O5]2.H2O: a theoretical perspective. AB - In this work, a potential semiorganic nonlinear optical candidate NH4B[D-(+) (C4H4O5)]2.H2O (NBC) has been studied using Density Functional Theory. The origin of the second harmonic generation (SHG) effect of NBC crystals for the NH4B[D-(+) (C4H4O5)]2.H2O molecular complex is explained by employing a combination of the density of states, SHG density and molecular orbital analysis. It reveals a way in which the organic and ammonium groups affect the SHG processes in a significantly different manner in the crystals and the molecular complex. In particular, the role of hydrogen bonding interaction in influencing the electronic structure and nonlinear optical properties is explicitly identified and explained. PMID- 25132526 TI - Detecting local residue environment similarity for recognizing near-native structure models. AB - We developed a new representation of local amino acid environments in protein structures called the Side-chain Depth Environment (SDE). An SDE defines a local structural environment of a residue considering the coordinates and the depth of amino acids that locate in the vicinity of the side-chain centroid of the residue. SDEs are general enough that similar SDEs are found in protein structures with globally different folds. Using SDEs, we developed a procedure called PRESCO (Protein Residue Environment SCOre) for selecting native or near native models from a pool of computational models. The procedure searches similar residue environments observed in a query model against a set of representative native protein structures to quantify how native-like SDEs in the model are. When benchmarked on commonly used computational model datasets, our PRESCO compared favorably with the other existing scoring functions in selecting native and near native models. PMID- 25132532 TI - Antifreezes act as catalysts for methane hydrate formation from ice. AB - Contrary to the thermodynamic inhibiting effect of methanol on methane hydrate formation from aqueous phases, hydrate forms quickly at high yield by exposing frozen water-methanol mixtures with methanol concentrations ranging from 0.6-10 wt% to methane gas at pressures from 125 bars at 253 K. Formation rates are some two orders of magnitude greater than those obtained for samples without methanol and conversion of ice is essentially complete. Ammonia has a similar catalytic effect when used in concentrations of 0.3-2.7 wt%. The structure I methane hydrate formed in this manner was characterized by powder X-ray diffraction and Raman spectroscopy. Steps in the possible mechanism of action of methanol were studied with molecular dynamics simulations of the Ih (0001) basal plane exposed to methanol and methane gas. Simulations show that methanol from a surface aqueous layer slowly migrates into the ice lattice. Methane gas is preferentially adsorbed into the aqueous methanol surface layer. Possible consequences of the catalytic methane hydrate formation on hydrate plug formation in gas pipelines, on large scale energy-efficient gas hydrate formation, and in planetary science are discussed. PMID- 25132525 TI - Neonatal handling: an overview of the positive and negative effects. AB - As one of the first rodent models designed to investigate the effects of early life experiences, the neonatal handling paradigm has helped us better understand how subtle changes in the infant environment can powerfully drive neurodevelopment of the immature brain in typical or atypical trajectories. Here, we review data from more than 50 years demonstrating the compelling effects of neonatal handling on behavior, physiology, and neural function across the lifespan. Moreover, we present data that challenge the classical view of neonatal handling as an animal model that results only in positive/beneficial outcomes. Indeed, the overall goal of this review is to offer the suggestion that the effects of early-life experiences-including neonatal handling-are nuanced rather than unidirectional. Both beneficial and negative outcomes may occur, depending on the parameters of testing, sex of the subject, and neurobehavioral system analyzed. PMID- 25132533 TI - Fine needle cytology of intrathyroid epidermoid cyst. PMID- 25132534 TI - Evaluation of microbial communities and symbionts in Ixodes ricinus and ungulate hosts (Cervus elaphus and Ovis aries) from shared habitats on the west coast of Norway. AB - Recent reports suggest a potential for transmission of a newly discovered rickettsial endosymbiont, Midichloria mitochondrii, to animals and humans from feeding ticks (Ixodes ricinus). Using molecular methods; I. ricinus, sheep and red deer in Anaplasma phagocytophilum-endemic areas of Norway, were examined to see if they were infected by M. mitochondrii or related organisms like Wolbachia pipientis and Rickettsia spp. A total of 532 ticks collected from pastures, 76 blood samples from grazing lambs and 12 organ samples from hunted deer, were analyzed during the study. All larval pools, 60.4% pooled nymphs and 35.1% of adult ticks were positive for M. mitochondrii. There was a significant difference between geographical areas in the prevalence of M. mitochondrii infection among nymphs. A total of 2.2% pooled nymphs and 5.3% adult ticks were positive for A. phagocytophilum. Eleven percent of pooled nymphs were positive for Borrelia spp, 2.2% of pooled nymphs and 3.5% of adult ticks were positive for Rickettsia spp. and none of the ticks were positive for W. pipientis. The prevalence of A. phagocytophilum infection was 54% and 75% in grazing lambs and deer, respectively. No animals were positive for Borrelia spp., M. mitochondrii, Rickettsia spp. or W. pipientis. The reported findings suggest that M. mitochondrii is widespread in tick populations at different geographical sites, and may appear in co-infection with A. phagocytophilum, Borrelia spp. and Rickettsia spp. in ticks. PMID- 25132535 TI - Detection of an undescribed Rickettsia sp. in Ixodes boliviensis from Costa Rica. AB - Ixodes boliviensis is a tick of carnivores that is common on domestic dogs. The only Rickettsia that has been detected previously in this species is 'Candidatus Rickettsia andeanae'. We report the detection of an undescribed Rickettsia sp., named strain IbR/CRC, in I. boliviensis collected from dogs in Costa Rica. Analyses of gltA, ompA, and htrA partial sequences place Rickettsia sp. strain IbR/CRC in the group of R. monacensis, also close to an endosymbiont of Ixodes scapularis and other undescribed rickettsiae. It was not possible to isolate Rickettsia sp. strain IbR/CRC in Vero E6 or C6/36 cell lines. Isolation and further characterization of Rickettsia sp. strain IbR/CRC and the other undescribed rickettsiae are required to determine their taxonomic status and pathogenic potential. PMID- 25132536 TI - Use of plastic tips in artificial feeding of Dermacentor (Anocentor) nitens females Neumann, 1897 (Acari: Ixodidae). AB - The establishment of laboratory colonies of ticks is often hampered by their lack of adaptation to alternative hosts. The aim of this study was to artificially feed partially engorged Dermacentor (Anocentor) nitens females through plastic tips, and to identify what are the optimal conditions of application of this technique to get as much as possible close to the natural conditions. The technique of artificial feeding through plastic tips allowed the engorgement of D. nitens ticks to a final weight within the normal range for the species. PMID- 25132537 TI - High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition. AB - Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.20/00). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such. PMID- 25132538 TI - Sequential infusion of donor-derived dendritic cells with donor lymphocyte infusion for relapsed hematologic cancers after allogeneic hematopoietic stem cell transplantation. AB - Donor lymphocyte infusion (DLI) is often given to induce a graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (HSCT). However, efficacy of DLI is limited in most hematologic cancers. As antigen presenting cells, dendritic cells (DC) bolster immune responses. We conducted a Phase I trial testing the coinfusion of DC followed by DLI. DC were generated by culturing peripheral blood mononuclear cells from HLA matched-related donors in GM-CSF and IL-4 for 7 days, followed by TNF-alpha for 3 days. DC were administered intravenously on 3 dose levels (5 * 10(6) ; 1 * 10(7) ; 5 * 10(7) cells). DLI (3 * 10(7) CD3+ cells/kg) was administered intravenously 1 day after the DC. Sixteen patients with hematologic cancers relapsed after HSCT were treated. A maximum tolerated dose for DC was not reached. Two of 16 patients met criteria for DLT within 10 weeks of the infusion: 1 idiopathic respiratory failure, 1 ventricular cardiac arrest. None developed grade III/IV GVHD. One patient developed grade II acute intestinal graft-vs.-host disease (GVHD) and 1 chronic GVHD within 6 months of the infusion. Both resolved with corticosteroids. Four of 14 patients evaluable for disease response achieved durable remissions and are alive and cancer free 6.7, 8.4, 8.8, and 10.1 years from infusion. Sequential infusion of donor-derived DC with DLI is feasible in patients with relapsed hematologic cancers after allogeneic HSCT. Future studies may consider donor DC preloaded with tumor antigens to investigate whether DC infusion could augment the GVL effect. PMID- 25132539 TI - Safety and efficacy of balloon-occluded transcatheter arterial chemoembolization using miriplatin for hepatocellular carcinoma. AB - AIM: Balloon-occluded transcatheter arterial chemoembolization (B-TACE) using a microballoon catheter was performed to administrate miriplatin, and the early therapeutic efficacy and safety of the procedure were evaluated. METHODS: Out of 158 patients who received miriplatin using B-TACE for hepatocellular carcinoma, 49 patients with a single lesion at either stage I or II (according to the Liver Cancer Study Group of Japan) were evaluated in comparison with 48 matched patients who received miriplatin using conventional TACE (C-TACE). RESULTS: The mean total dose and median dose of miriplatin in each group were 32.5 +/- 31.7 mg and 20 mg (C-TACE) and 50.1 +/- 31.3 mg and 40 mg (B-TACE), respectively (P < 0.01). The treatment effect (TE) on the target nodule classified as TE4, TE3, TE2 or TE1 was 39.6%, 33.3%, 25.0% and 2.1%, respectively, in the C-TACE group, and 55.1%, 38.8%, 4.1% and 2.0%, respectively, in the B-TACE group. Therefore, the TE was significantly higher in the B-TACE group (P < 0.05). Although abdominal blood tests revealed adverse, increased levels of serum alanine aminotransferase (ALT) in a significantly higher number of B-TACE-treated patients, serum ALT levels returned to baseline levels in all patients within 1 month. There were no significant differences in clinical symptoms between the two groups. CONCLUSION: Compared with C-TACE, B-TACE significantly improved cancer nodule control, and it was satisfactory in terms of safety. B-TACE is an effective procedure that enhances the effects of catheterization with miriplatin. PMID- 25132540 TI - Influence of fluoride in poly(d,l-lactide)/apatite composites on bone formation. AB - The influence of fluoride in poly(d,l-lactide)/apatite composites on ectopic bone formation was evaluated in sheep. Nano-apatite powders with different replacement levels of OH groups by fluoride (F) (0% (F0), 50% (F50), 100% (F100), and excessive (F200)) were co-extruded with poly (d,l-lactide) at a weight ratio of 1:1. Fluoride release from the composites (CF0, CF50, CF100, and CF200) was evaluated in vitro and bone formation was assessed after intramuscular implantation in sheep. After 24 weeks in simulated physiological solution, CF0 and CF50 showed negligible fluoride release, whereas it was considerable from the CF100 and CF200 composites. Histology showed that the incidence of de novo bone formation decreased in implants with increasing fluoride content indicating a negative influence of fluoride on ectopic bone formation. Furthermore, a significant decrease in resorption of the high fluoride-content composites and a reduction in the number of multinucleated giant cells were seen. These results show that instead of promoting, the presence of fluoride in poly(d,l lactide)/apatite composites seemed to suppresses their resorption and osteoinductive potential in non-osseous sites. PMID- 25132541 TI - Interparental violence and childhood adjustment: how and why maternal sensitivity is a protective factor. AB - This study examined sensitive parenting as a protective factor in relations between interparental violence (IPV) and children's coping and psychological adjustment. Using a multimethod approach, a high-risk sample of 201 two-year-olds and their mothers participated in three annual waves of data collection. Moderator analyses revealed that sensitive parenting buffered the risk posed by IPV on children's changes in externalizing and prosocial development over a 2 year period. Tests of mediated moderation further indicated that sensitive parenting protected children from the vulnerability of growing up in a violent home through its association with lower levels of children's angry reactivity to interparental conflict. Results highlight the significance of identifying the mechanisms that mediate protective factors in models of family adversity. PMID- 25132543 TI - Community perceptions of rape and child sexual abuse: a qualitative study in rural Tanzania. AB - BACKGROUND: Rape of women and children is recognized as a health and human rights issue in Tanzania and internationally. Exploration of the prevailing perceptions in rural areas is needed in order to expand the understanding of sexual violence in the diversity of Tanzania's contexts. The aim of this study therefore was to explore and understand perceptions of rape of women and children at the community level in a rural district in Tanzania with the added objective of exploring those perceptions that may contribute to perpetuating and/or hindering the disclosure of rape incidences. METHODS: A qualitative design was employed using focus group discussions with male and female community members including religious leaders, professionals, and other community members. The discussions centered on causes of rape, survivors of rape, help-seeking and reporting, and gathered suggestions on measures for improvement. Six focus group discussions (four of single gender and two of mixed gender) were conducted. The focus group discussions were recorded, transcribed verbatim, and analyzed using manifest qualitative content analysis. RESULTS: The participants perceived rape of women and children to be a frequent and hidden phenomenon. A number of factors were singled out as contributing to rape, such as erosion of social norms, globalization, poverty, vulnerability of children, alcohol/drug abuse and poor parental care. Participants perceived the need for educating the community to raise their knowledge of sexual violence and its consequences, and their roles as preventive agents. CONCLUSIONS: In this rural context, social norms reinforce sexual violence against women and children, and hinder them from seeking help from support services. Addressing the identified challenges may promote help-seeking behavior and improve care of survivors of sexual violence, while changes in social and cultural norms are needed for the prevention of sexual violence. PMID- 25132542 TI - Description of Kuraishia piskuri f.a., sp. nov., a new methanol assimilating yeast and transfer of phylogenetically related Candida species to the genera Kuraishia and Nakazawaea as new combinations. AB - The new anamorphic yeast Kuraishia piskuri, f.a., sp. nov. is described for three strains that were isolated from insect frass from trees growing in Florida, USA (type strain, NRRL YB-2544, CBS 13714). Species placement was based on phylogenetic analysis of nuclear gene sequences for the D1/D2 domains of large subunit rRNA, small subunit rRNA, translation elongation factor-1alpha, and subunits B1 and B2 of RNA polymerase II B. From this analysis, the anamorphic species Candida borneana, Candida cidri, Candida floccosa, Candida hungarica, and Candida ogatae were transferred to the genus Kuraishia as new combinations and Candida anatomiae, Candida ernobii, Candida ishiwadae, Candida laoshanensis, Candida molendini-olei, Candida peltata, Candida pomicola, Candida populi, Candida wickerhamii, and Candida wyomingensis were transferred to the genus Nakazawaea. PMID- 25132544 TI - Role of sediments in modifying the toxicity of two Roundup formulations to six species of larval anurans. AB - The role of sediment in modifying the toxicity of the original formulation of Roundup(r) and Roundup WeatherMAX(r) was examined in aqueous laboratory tests. Six species of anurans (Bufo fowleri, Hyla chrysoscelis, Rana catesbeiana, Rana clamitans, Rana sphenocephala, and Rana pipiens) were exposed at Gosner stage 25 to concentrations of the 2 herbicide formulations in 96-h, static, nonrenewal experiments in the presence and absence of sediment. All species tested had lower median lethal concentration values in water-only exposures of both formulations compared with exposures with sediment. Sediment significantly altered the potency slopes in all tests with the exceptions of H. chrysoscelis and R. clamitans when exposed to the original formulation of Roundup and H. chrysoscelis and R. sphenocephala when exposed to Roundup WeatherMAX. Thresholds were significantly different in all tests, including those in which potency slopes did not differ. Based on water-sediment exposures of the original formulation of Roundup, all 6 species tested had a margin of safety when compared with the predicted environmental concentration of the highest label application rate. Of the 6 species, 5 had a margin of safety when exposed to Roundup WeatherMAX. During incidental exposures in the field, sediments and organic matter present in aquatic systems provide significant sources of environmental ligands. If used according to label instructions, both herbicides should pose minimal risk to anuran amphibians in actual field applications. Environ Toxicol Chem 2014;33:2616 2620. (c) 2014 SETAC. PMID- 25132545 TI - Structure and mechanism of Zn2+-transporting P-type ATPases. AB - Zinc is an essential micronutrient for all living organisms. It is required for signalling and proper functioning of a range of proteins involved in, for example, DNA binding and enzymatic catalysis. In prokaryotes and photosynthetic eukaryotes, Zn(2+)-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn(2+) and related elements. Here we present crystal structures representing the phosphoenzyme ground state (E2P) and a dephosphorylation intermediate (E2.Pi) of ZntA from Shigella sonnei, determined at 3.2 A and 2.7 A resolution, respectively. The structures reveal a similar fold to Cu(+)-ATPases, with an amphipathic helix at the membrane interface. A conserved electronegative funnel connects this region to the intramembranous high-affinity ion-binding site and may promote specific uptake of cellular Zn(2+) ions by the transporter. The E2P structure displays a wide extracellular release pathway reaching the invariant residues at the high affinity site, including C392, C394 and D714. The pathway closes in the E2.Pi state, in which D714 interacts with the conserved residue K693, which possibly stimulates Zn(2+) release as a built-in counter ion, as has been proposed for H(+)-ATPases. Indeed, transport studies in liposomes provide experimental support for ZntA activity without counter transport. These findings suggest a mechanistic link between PIB-type Zn(2+)-ATPases and PIII-type H(+)-ATPases and at the same time show structural features of the extracellular release pathway that resemble PII-type ATPases such as the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+), K(+)-ATPase. These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine. PMID- 25132546 TI - Hallucigenia's onychophoran-like claws and the case for Tactopoda. AB - The Palaeozoic form-taxon Lobopodia encompasses a diverse range of soft-bodied 'legged worms' known from exceptional fossil deposits. Although lobopodians occupy a deep phylogenetic position within Panarthropoda, a shortage of derived characters obscures their evolutionary relationships with extant phyla (Onychophora, Tardigrada and Euarthropoda). Here we describe a complex feature in the terminal claws of the mid-Cambrian lobopodian Hallucigenia sparsa--their construction from a stack of constituent elements--and demonstrate that equivalent elements make up the jaws and claws of extant Onychophora. A cladistic analysis, informed by developmental data on panarthropod head segmentation, indicates that the stacked sclerite components in these two taxa are homologous resolving hallucigeniid lobopodians as stem-group onychophorans. The results indicate a sister-group relationship between Tardigrada and Euarthropoda, adding palaeontological support to the neurological and musculoskeletal evidence uniting these disparate clades. These findings elucidate the evolutionary transformations that gave rise to the panarthropod phyla, and expound the lobopodian-like morphology of the ancestral panarthropod. PMID- 25132547 TI - Synaptic dysregulation in a human iPS cell model of mental disorders. AB - Dysregulated neurodevelopment with altered structural and functional connectivity is believed to underlie many neuropsychiatric disorders, and 'a disease of synapses' is the major hypothesis for the biological basis of schizophrenia. Although this hypothesis has gained indirect support from human post-mortem brain analyses and genetic studies, little is known about the pathophysiology of synapses in patient neurons and how susceptibility genes for mental disorders could lead to synaptic deficits in humans. Genetics of most psychiatric disorders are extremely complex due to multiple susceptibility variants with low penetrance and variable phenotypes. Rare, multiply affected, large families in which a single genetic locus is probably responsible for conferring susceptibility have proven invaluable for the study of complex disorders. Here we generated induced pluripotent stem (iPS) cells from four members of a family in which a frameshift mutation of disrupted in schizophrenia 1 (DISC1) co-segregated with major psychiatric disorders and we further produced different isogenic iPS cell lines via gene editing. We showed that mutant DISC1 causes synaptic vesicle release deficits in iPS-cell-derived forebrain neurons. Mutant DISC1 depletes wild-type DISC1 protein and, furthermore, dysregulates expression of many genes related to synapses and psychiatric disorders in human forebrain neurons. Our study reveals that a psychiatric disorder relevant mutation causes synapse deficits and transcriptional dysregulation in human neurons and our findings provide new insight into the molecular and synaptic etiopathology of psychiatric disorders. PMID- 25132548 TI - Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies. AB - Invasion of host erythrocytes is essential to the life cycle of Plasmodium parasites and development of the pathology of malaria. The stages of erythrocyte invasion, including initial contact, apical reorientation, junction formation, and active invagination, are directed by coordinated release of specialized apical organelles and their parasite protein contents. Among these proteins, and central to invasion by all species, are two parasite protein families, the reticulocyte-binding protein homologue (RH) and erythrocyte-binding like proteins, which mediate host-parasite interactions. RH5 from Plasmodium falciparum (PfRH5) is the only member of either family demonstrated to be necessary for erythrocyte invasion in all tested strains, through its interaction with the erythrocyte surface protein basigin (also known as CD147 and EMMPRIN). Antibodies targeting PfRH5 or basigin efficiently block parasite invasion in vitro, making PfRH5 an excellent vaccine candidate. Here we present crystal structures of PfRH5 in complex with basigin and two distinct inhibitory antibodies. PfRH5 adopts a novel fold in which two three-helical bundles come together in a kite-like architecture, presenting binding sites for basigin and inhibitory antibodies at one tip. This provides the first structural insight into erythrocyte binding by the Plasmodium RH protein family and identifies novel inhibitory epitopes to guide design of a new generation of vaccines against the blood-stage parasite. PMID- 25132552 TI - A 400-solar-mass black hole in the galaxy M82. AB - M82 X-1, the brightest X-ray source in the galaxy M82, has been thought to be an intermediate-mass black hole (100 to 10,000 solar masses) because of its extremely high luminosity and variability characteristics, although some models suggest that its mass may be only about 20 solar masses. The previous mass estimates were based on scaling relations that use low-frequency characteristic timescales which have large intrinsic uncertainties. For stellar-mass black holes, we know that the high-frequency quasi-periodic oscillations (100-450 hertz) in the X-ray emission that occur in a 3:2 frequency ratio are stable and scale in frequency inversely with black hole mass with a reasonably small dispersion. The discovery of such stable oscillations thus potentially offers an alternative and less ambiguous means of mass determination for intermediate-mass black holes, but has hitherto not been realized. Here we report stable, twin-peak (3:2 frequency ratio) X-ray quasi-periodic oscillations from M82 X-1 at frequencies of 3.32 +/- 0.06 hertz and 5.07 +/- 0.06 hertz. Assuming that we can extrapolate the inverse-mass scaling that holds for stellar-mass black holes, we estimate the black hole mass of M82 X-1 to be 428 +/- 105 solar masses. In addition, we can estimate the mass using the relativistic precession model, from which we get a value of 415 +/- 63 solar masses. PMID- 25132549 TI - Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. AB - T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a dismal overall prognosis, including a relapse rate of up to 25%, mainly because of the lack of non-cytotoxic targeted therapy options. Drugs that target the function of key epigenetic factors have been approved in the context of haematopoietic disorders, and mutations that affect chromatin modulators in a variety of leukaemias have recently been identified; however, 'epigenetic' drugs are not currently used for T-ALL treatment. Recently, we described that the polycomb repressive complex 2 (PRC2) has a tumour-suppressor role in T-ALL. Here we delineated the role of the histone 3 lysine 27 (H3K27) demethylases JMJD3 and UTX in T-ALL. We show that JMJD3 is essential for the initiation and maintenance of T-ALL, as it controls important oncogenic gene targets by modulating H3K27 methylation. By contrast, we found that UTX functions as a tumour suppressor and is frequently genetically inactivated in T-ALL. Moreover, we demonstrated that the small molecule inhibitor GSKJ4 (ref. 5) affects T-ALL growth, by targeting JMJD3 activity. These findings show that two proteins with a similar enzymatic function can have opposing roles in the context of the same disease, paving the way for treating haematopoietic malignancies with a new category of epigenetic inhibitors. PMID- 25132550 TI - RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. AB - Necroptosis has emerged as an important pathway of programmed cell death in embryonic development, tissue homeostasis, immunity and inflammation. RIPK1 is implicated in inflammatory and cell death signalling and its kinase activity is believed to drive RIPK3-mediated necroptosis. Here we show that kinase independent scaffolding RIPK1 functions regulate homeostasis and prevent inflammation in barrier tissues by inhibiting epithelial cell apoptosis and necroptosis. Intestinal epithelial cell (IEC)-specific RIPK1 knockout caused IEC apoptosis, villus atrophy, loss of goblet and Paneth cells and premature death in mice. This pathology developed independently of the microbiota and of MyD88 signalling but was partly rescued by TNFR1 (also known as TNFRSF1A) deficiency. Epithelial FADD ablation inhibited IEC apoptosis and prevented the premature death of mice with IEC-specific RIPK1 knockout. However, mice lacking both RIPK1 and FADD in IECs displayed RIPK3-dependent IEC necroptosis, Paneth cell loss and focal erosive inflammatory lesions in the colon. Moreover, a RIPK1 kinase inactive knock-in delayed but did not prevent inflammation caused by FADD deficiency in IECs or keratinocytes, showing that RIPK3-dependent necroptosis of FADD-deficient epithelial cells only partly requires RIPK1 kinase activity. Epidermis-specific RIPK1 knockout triggered keratinocyte apoptosis and necroptosis and caused severe skin inflammation that was prevented by RIPK3 but not FADD deficiency. These findings revealed that RIPK1 inhibits RIPK3-mediated necroptosis in keratinocytes in vivo and identified necroptosis as a more potent trigger of inflammation compared with apoptosis. Therefore, RIPK1 is a master regulator of epithelial cell survival, homeostasis and inflammation in the intestine and the skin. PMID- 25132551 TI - Transcriptional interference by antisense RNA is required for circadian clock function. AB - Eukaryotic circadian oscillators consist of negative feedback loops that generate endogenous rhythmicities. Natural antisense RNAs are found in a wide range of eukaryotic organisms. Nevertheless, the physiological importance and mode of action of most antisense RNAs are not clear. frequency (frq) encodes a component of the Neurospora core circadian negative feedback loop, which was thought to generate sustained rhythmicity. Transcription of qrf, the long non-coding frq antisense RNA, is induced by light, and its level oscillates in antiphase to frq sense RNA. Here we show that qrf transcription is regulated by both light dependent and light-independent mechanisms. Light-dependent qrf transcription represses frq expression and regulates clock resetting. Light-independent qrf expression, on the other hand, is required for circadian rhythmicity. frq transcription also inhibits qrf expression and drives the antiphasic rhythm of qrf transcripts. The mutual inhibition of frq and qrf transcription thus forms a double negative feedback loop that is interlocked with the core feedback loop. Genetic and mathematical modelling analyses indicate that such an arrangement is required for robust and sustained circadian rhythmicity. Moreover, our results suggest that antisense transcription inhibits sense expression by mediating chromatin modifications and premature termination of transcription. Taken together, our results establish antisense transcription as an essential feature in a circadian system and shed light on the importance and mechanism of antisense action. PMID- 25132553 TI - Proteomic and metabolomic profiling of Valencia orange fruit after natural frost exposure. AB - The aim of this study was to evaluate the response of orange fruit (Citrus sinensis var. Valencia Late) to freezing stress in planta, both immediately after the natural event and after a week, in order to understand the biochemical and molecular basis of the changes that later derive in internal and external damage symptoms. Using two-dimensional differential gel electrophoresis to analyze exposed and non-exposed fruit, 27 differential protein spots were detected in juice sacs and flavedo, among all comparisons made. Also, primary and secondary metabolites relative contents were analyzed in both tissues by gas chromatography mass spectrometry and liquid chromatography-mass spectrometry, respectively. Proteins and compounds involved in regulatory functions, iron metabolism, oxidative damage and carbohydrate metabolism were the most affected. Interestingly, three glycolytic enzymes were induced by cold, and there was an increase in fermentation products (volatiles); all of that suggests that more energy generation might be required from glycolysis to counter the cold stress. Moreover, a notable increase in sugar levels was observed after frost, but it was not at the expense of organic acids utilization. Consequently, these results suggest a probable redistribution of photoassimilates in the frost-exposed plants, tending to restore the homeostasis altered by that severe type of stress. Isosinensetin was the most cold-sensitive secondary metabolite because it could not be detected at all after the frost, constituting a possible tool to early diagnose freezing damage. PMID- 25132555 TI - Expression, pharmacology and functional activity of adenosine A1 receptors in genetic models of Huntington's disease. AB - Adenosine A1 receptor (A1R) stimulation exerts beneficial effects in response to various insults to the brain and, although it was found neuroprotective in a lesional model of Huntington's disease (HD), the features of this receptor in genetic models of HD have never been explored. In the present study we characterized the expression, affinity and functional effects of A1Rs in R6/2 mice (the most widely used transgenic model of HD) and in a cellular model of HD. Binding studies revealed that the density of A1Rs was significantly reduced in the cortex and the striatum of R6/2 mice compared to age-matched wild-type (WT), while receptor affinity was unchanged. The selective A1R agonist cyclopentyladenosine (CPA, 300nM) was significantly more effective in reducing synaptic transmission in corticostriatal slices from symptomatic R6/2 than in age matched WT mice. Such an effect was due to a stronger inhibition of glutamate release from the pre-synaptic terminal. The different functional activities of A1Rs in HD mice were associated also to a different intracellular signaling pathway involved in the synaptic effect of CPA. In fact, while the PKA pathway was involved in both genotypes, p38 MAPK inhibitor SB203580 partially prevented synaptic effects of CPA in R6/2, but not in WT, mice; moreover, CPA differently modulated the phosphorylation status of p38 in the two genotypes. In vitro studies confirmed a different behavior of A1Rs in HD: CPA (100 nM for 5h) modulated cell viability in STHdh(Q111/Q111) (mhttHD cells), without affecting the viability of STHdh(Q7/Q7) (wthtt cells). This effect was prevented by the application of SB203580. Our results demonstrate that in the presence of the HD mutation A1Rs undergo profound changes in terms of expression, pharmacology and functional activity. These changes have to be taken in due account when considering A1Rs as a potential therapeutic target for this disease. PMID- 25132556 TI - Effects of diet-induced obesity and voluntary exercise in a tauopathy mouse model: implications of persistent hyperleptinemia and enhanced astrocytic leptin receptor expression. AB - The number of patients with Alzheimer's disease (AD) is increasing worldwide, and available drugs have shown limited efficacy. Hence, preventive interventions and treatments for presymptomatic AD are currently considered very important. Obesity rates have also been increasing dramatically and it is an independent risk factor of AD. Therefore, for the prevention of AD, it is important to elucidate the pathomechanism between obesity and AD. We generated high calorie diet (HCD) induced obese tauopathy model mice (PS19), which showed hyperleptinemia but limited insulin resistance. HCD enhanced tau pathology and glial activation. Conversely, voluntary exercise with a running wheel normalized the serum leptin concentration without reducing body weight, and restored the pathological changes induced by HCD. Thus, we speculated that persistent hyperleptinemia played an important role in accelerating pathological changes in PS19 mice. Leptin primarily regulates food intake and body weight via leptin receptor b (LepRb). Interestingly, the nuclear staining for p-STAT3, which was activated by LepRb, was decreased in hippocampal neurons in HCD PS19 mice, indicating leptin resistance. Meanwhile, astroglial activation and the astrocytic expression of a short LepR isoform, LepRa, were enhanced in the hippocampus of HCD PS19 mice. Real-time PCR analysis demonstrated that leptin increased mRNA levels for pro inflammatory cytokines including IL-1beta and TNF-alpha in primary cultured astrocytes from wild type and LepRb-deficient mice. These observations suggest that persistent hyperleptinemia caused by obesity induces astrocytic activation, astrocytic leptin hypersensitivity with enhanced LepRa expression, and enhanced inflammation, consequently accelerating tau pathology in PS19 mice. PMID- 25132558 TI - Self-consistent Green's function method for dilute nitride conduction band structure. AB - We present a self-consistent Green's function (SCGF) approach for the Anderson many-impurity model to calculate the band dispersion and density of states near the conduction band edge in GaN(x)As(1-x) dilute nitride alloys. Two different models of the N states have been studied to investigate the band structure of these materials: (1) the two-band model, which assumes all N states have the same energy, EN; (2) a model which includes a full distribution of N states obtained by allowing for direct interaction between N sites. The density of states, projected onto extended and localised states, calculated by the SCGF two-band model, are in excellent agreement with those previously obtained in supercell calculations and reveal a gap in the density of states just above E(N), in contrast with the results of previous non-self-consistent Green's function calculations. However, including the full distribution of N states in a SCGF calculation removes this gap, in agreement with experiment. PMID- 25132554 TI - Animal models of absence epilepsies: what do they model and do sex and sex hormones matter? AB - While epidemiological data suggest a female prevalence in human childhood- and adolescence-onset typical absence epilepsy syndromes, the sex difference is less clear in adult-onset syndromes. In addition, although there are more females than males diagnosed with typical absence epilepsy syndromes, there is a paucity of studies on sex differences in seizure frequency and semiology in patients diagnosed with any absence epilepsy syndrome. Moreover, it is unknown if there are sex differences in the prevalence or expression of atypical absence epilepsy syndromes. Surprisingly, most studies of animal models of absence epilepsy either did not investigate sex differences, or failed to find sex-dependent effects. However, various rodent models for atypical syndromes such as the AY9944 model (prepubertal females show a higher incidence than prepubertal males), BN model (also with a higher prevalence in males) and the Gabra1 deletion mouse in the C57BL/6J strain offer unique possibilities for the investigation of the mechanisms involved in sex differences. Although the mechanistic bases for the sex differences in humans or these three models are not yet known, studies of the effects of sex hormones on seizures have offered some possibilities. The sex hormones progesterone, estradiol and testosterone exert diametrically opposite effects in genetic absence epilepsy and pharmacologically-evoked convulsive types of epilepsy models. In addition, acute pharmacological effects of progesterone on absence seizures during proestrus are opposite to those seen during pregnancy. 17beta-Estradiol has anti-absence seizure effects, but it is only active in atypical absence models. It is speculated that the pro-absence action of progesterone, and perhaps also the delayed pro-absence action of testosterone, are mediated through the neurosteroid allopregnanolone and its structural and functional homolog, androstanediol. These two steroids increase extrasynaptic thalamic tonic GABAergic inhibition by selectively targeting neurosteroid selective subunits of GABAA receptors (GABAARs). Neurosteroids also modulate the expression of GABAAR containing the gamma2, alpha4, and delta subunits. It is hypothesized that differences in subunit expression during pregnancy and ovarian cycle contribute to the opposite effects of progesterone in these two hormonal states. PMID- 25132559 TI - Lead and trace element levels in placenta, maternal and cord blood: a cross sectional pilot study. AB - AIM: To determine lead (Pb) and trace element (Fe, Zn, Cu, Mg) levels in placenta, maternal and cord blood; further, to assess the interactions between Pb and trace elements, if any. METHODS: A cluster of 'at term pregnant women' from rural and urban areas (n = 30 each, total n = 60) as well as their neonates after delivery were recruited. Maternal blood, heel prick neonatal blood, placenta and cord blood were collected at the time of parturition. Pb and trace element levels in blood/serum, placenta were determined on graphite furnace atomic absorption (AAS) and flame AAS respectively. Due to sample constraints, only Pb levels were determined in heel prick blood samples of neonates. RESULTS: There were no major abnormal signs and symptoms, however, 38% had pale conjunctiva and 13% had pigmented tongue. The blood lead levels (BLL) were significantly (P < 0.05) higher in urban post-partum women compared to their rural counterparts. Higher BLL did not correlate with either pregnancy outcome or neonatal anthropometry. Maternal serum trace element levels were deficient in both rural and urban women. Significant (P < 0.01) positive correlation between maternal and neonatal BLL as well as significant (P < 0.05) inverse correlation between cord BLL and placental Pb levels were observed. Maternal and cord BLL correlated inversely (P < 0.05) with maternal and cord serum Fe levels, respectively. CONCLUSION: Urban post partum women and their neonates were at higher risk with elevated BLL. Estimate of cord blood Pb may not be the true index of neonatal BLL. These observations must be confirmed in a larger cohort because prenatal/neonatal screening avoids the risks associated with rest of life. PMID- 25132557 TI - Combinatorial targeting of early pathways profoundly inhibits neurodegeneration in a mouse model of glaucoma. AB - The endothelin system is implicated in various human and animal glaucomas. Targeting the endothelin system has great promise as a treatment for human glaucoma, but the cell types involved and the exact mechanisms of action are not clearly elucidated. Here, we report a detailed characterization of the endothelin system in specific cell types of the optic nerve head (ONH) during glaucoma in DBA/2J mice. First, we show that key components of the endothelin system are expressed in multiple cell types. We discover that endothelin 2 (EDN2) is expressed in astrocytes as well as microglia/monocytes in the ONH. The endothelin receptor type A (Ednra) is expressed in vascular endothelial cells, while the endothelin receptor type B (Ednrb) receptor is expressed in ONH astrocytes. Second, we show that Macitentan treatment protects from glaucoma. Macitentan is a novel, orally administered, dual endothelin receptor antagonist with greater affinity, efficacy and safety than previous antagonists. Finally, we test the combinatorial effect of targeting both the endothelin and complement systems as a treatment for glaucoma. Similar to endothelin, the complement system is implicated in a variety of human and animal glaucomas, and has great promise as a treatment target. We discovered that combined targeting of the endothelin (Bosentan) and complement (C1qa mutation) systems is profoundly protective. Remarkably, 80% of DBA/2J eyes subjected to this combined inhibition developed no detectable glaucoma. This opens an exciting new avenue for neuroprotection in glaucoma. PMID- 25132560 TI - Antagonistic evolution in an aposematic predator-prey signaling system. AB - Warning signals within species, such as the bright colors of chemically defended animals, are usually considered mutualistic, monomorphic traits. Such a view is however increasingly at odds with the growing empirical literature, showing nontrivial levels of signal variation within prey populations. Key to understanding this variation, we argue, could be a recognition that toxicity levels frequently vary within populations because of environmental heterogeneity. Inequalities in defense may undermine mutualistic monomorphic signaling, causing evolutionary antagonism between loci that determine appearance of less well defended and better defended prey forms within species. In this article, we apply a stochastic model of evolved phenotypic plasticity to the evolution of prey signals. We show that when toxicity levels vary, then antagonistic interactions can lead to evolutionary conflict between alleles at different signaling loci, causing signal evolution, "red queen-like" evolutionary chase, and one or more forms of signaling equilibria. A key prediction is that variation in the way that predators use information about toxicity levels in their attack behaviors profoundly affects the evolutionary characteristics of the prey signaling systems. Environmental variation is known to cause variation in many qualities that organisms signal; our approach may therefore have application to other signaling systems. PMID- 25132562 TI - Development of a sensitive amplified luminescent proximity homogeneous assay to monitor the interactions between pTEFb and Tat. AB - The viral transactivator protein (Tat) plays an essential role in the replication of human immunodeficiency type 1 virus (HIV-1) by recruiting the host positive transcription elongation factor (pTEFb) to the RNA polymerase II transcription machinery to enable an efficient HIV-1 RNA elongation process. Blockade of the interaction between Tat and pTEFb represents a novel strategy for developing a new class of antiviral agents. In this study, we developed a homogeneous assay in AlphaLISA (amplified luminescent proximity homogeneous assay) format using His tagged pTEFb and biotinylated Tat to monitor the interaction between Tat and pTEFb. On optimizing the assay conditions, the signal-to-background ratio was found to be greater than 10-fold. The assay was validated with untagged Tat and peptides known to compete with Tat for pTEFb binding. The Z' of the assay is greater than 0.5, indicating that the assay is robust and can be easily adapted to a high-throughput screening format. Furthermore, the affinity between Tat and pTEFb was determined to be approximately 20 pM, and only 7% of purified Tat was found to be active in forming tertiary complex with pTEFb. Development of this assay should facilitate the discovery of a new class of antiviral agents providing HIV-1 patients with broader treatment choices. PMID- 25132563 TI - Sensitive detection of acetylcholine based on a novel boronate intramolecular charge transfer fluorescence probe. AB - A highly sensitive and selective fluorescence method for the detection of acetylcholine (ACh) based on enzyme-generated hydrogen peroxide (H2O2) and a new boronate intramolecular charge transfer (ICT) fluorescence probe, 4-(4,4,5,5 tetramethyl-1,3,2-dioxaborolan-2-yl)-N-butyl-1,8-naphthalimide (BN), was developed. This strategy involves the reaction of ACh with acetylcholinesterase (AChE) to produce choline, which is further oxidized by choline oxidase (ChOx) to obtain betaine and H2O2. The enzyme-generated H2O2 reacts with BN and results in hydrolytic deprotection of BN to generate fluorescent product (4-hydroxyl-N-butyl 1,8-naphthalimide, ON). Two consecutive linear response ranges allow determining ACh in a wide concentration range with a low detection limit of 2.7 nM (signal/noise=3). Compared with other fluorescent probes based on the mechanism of nonspecific oxidation, this reported boronate probe has the advantage of no interference from other biologically relevant reactive oxygen species (ROS) on the detection of ACh. This study provides a new method for the detection of ACh with high selectivity and sensitivity. PMID- 25132564 TI - Capillary isoelectric focusing of a difficult-to-denature tetrameric enzyme using alkylurea-urea mixtures. AB - Capillary isoelectric focusing (cIEF) is normally run under denaturing conditions using urea to expose any buried protein residues that may contribute to the overall charge. However, urea does not completely denature some proteins, such as the tetrameric enzyme Erwinia chrysanthemil-asparaginase (ErA), in which case electrophoresis-compatible alternative denaturants are required. Here, we show that alkylureas such as N-ethylurea provide increased denaturation during cIEF. The cIEF analysis of ErA in 8 M urea alone resulted in a cluster of ill-resolved peaks with isoelectric points (pI values) in the range 7.4 to 8.5. A combination of 2.0 to 2.2 M N-ethylurea and 8M urea provided sufficient denaturation of ErA, resulting in a main peak with a pI of 7.35 and an acidic species minor peak at 7.0, both comparing well with predicted pI values based on the sum of protein residue pKa values. Recombinant deamidated ErA mutants were also demonstrated to migrate to pI values consistent with predictions (pI 7.0 for one deamidation). The quantitation of ErA acidic species in samples from full-scale manufacturing (1.0-3.5% of total peak area) was found to be reproducible and linear. Use of alkylureas as denaturing agents in capillary electrophoresis and cIEF should be considered during biopharmaceutical assay development. PMID- 25132565 TI - Correction for concentration overestimation of nucleic acids with phenol. AB - We report a computational method based on ultraviolet (UV) spectra for correcting the overestimated concentrations of nucleic acid samples contaminated with TRIzol/phenol. The derived correction formulas were validated using RNA solutions, double-stranded DNA solutions, and single-stranded oligonucleotide solutions. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) with SYBR Green was performed to assess the level of TRIzol contamination that can be tolerated for gene expression quantification. After the correction, the accuracy of the RNA concentrations was greatly improved and there was no significant difference in the threshold cycle (Ct) values for GAPDH and ACAN genes in RT-qPCR obtained for RNA contaminated with up to 0.1% TRIzol (phenol level index [PLI]~5.8-5.9). Similarly, accuracy improvements were also observed for DNA or oligonucleotides contaminated with phenol using different concentration correction formulas. In addition, the Ct values and amplification efficiency of DNA in qPCR were not affected by TRIzol contamination below 1%. This computational method is easy and convenient to use and reduces the concentration overestimations greatly. PMID- 25132561 TI - Connections between TET proteins and aberrant DNA modification in cancer. AB - DNA methylation has been linked to aberrant silencing of tumor suppressor genes in cancer, and an imbalance in DNA methylation-demethylation cycles is intimately implicated in the onset and progression of tumors. Ten-eleven translocation (TET) proteins are Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenases that successively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5 formylcytosine (5fC), and 5-carboxylcytosine (5caC), thereby mediating active DNA demethylation. In this review, we focus on the pathophysiological role of TET proteins and 5hmC in cancer. We present an overview of loss-of-function mutations and abnormal expression and regulation of TET proteins in hematological malignancies and solid tumors, and discuss the potential prognostic value of assessing TET mutations and 5hmC levels in cancer patients. We also address the crosstalk between TET and two critical enzymes involved in cell metabolism: O linked beta-N-acetylglucosamine transferase (OGT) and isocitrate dehydrogenase (IDH). Lastly, we discuss the therapeutic potential of targeting TET proteins and aberrant DNA methylation in cancer. PMID- 25132566 TI - Molecular identification and phylogenetic study of Demodex caprae. AB - The DNA barcode has been widely used in species identification and phylogenetic analysis since 2003, but there have been no reports in Demodex. In this study, to obtain an appropriate DNA barcode for Demodex, molecular identification of Demodex caprae based on mitochondrial cox1 was conducted. Firstly, individual adults and eggs of D. caprae were obtained for genomic DNA (gDNA) extraction; Secondly, mitochondrial cox1 fragment was amplified, cloned, and sequenced; Thirdly, cox1 fragments of D. caprae were aligned with those of other Demodex retrieved from GenBank; Finally, the intra- and inter-specific divergences were computed and the phylogenetic trees were reconstructed to analyze phylogenetic relationship in Demodex. Results obtained from seven 429-bp fragments of D. caprae showed that sequence identities were above 99.1% among three adults and four eggs. The intraspecific divergences in D. caprae, Demodex folliculorum, Demodex brevis, and Demodex canis were 0.0-0.9, 0.5-0.9, 0.0-0.2, and 0.0-0.5%, respectively, while the interspecific divergences between D. caprae and D. folliculorum, D. canis, and D. brevis were 20.3-20.9, 21.8-23.0, and 25.0-25.3, respectively. The interspecific divergences were 10 times higher than intraspecific ones, indicating considerable barcoding gap. Furthermore, the phylogenetic trees showed that four Demodex species gathered separately, representing independent species; and Demodex folliculorum gathered with canine Demodex, D. caprae, and D. brevis in sequence. In conclusion, the selected 429-bp mitochondrial cox1 gene is an appropriate DNA barcode for molecular classification, identification, and phylogenetic analysis of Demodex. D. caprae is an independent species and D. folliculorum is closer to D. canis than to D. caprae or D. brevis. PMID- 25132567 TI - Silver nanoparticles: a possibility for malarial and filarial vector control technology. AB - Green synthesis technology is one of the rapid, reliable and best routes for the synthesis of silver nanoparticles (AgNPs). There are bioactive compounds with enormous potential in Azadirachta indica (Neem). The extraordinary mosquitoes warrant nanotechnology to integrate with novel molecules. This will be sustainable technology for future. Here, we synthesized AgNPs using aqueous extracts of leaves and bark of Az. indica (Neem). We tested AgNPs as larvicides, pupicides and adulticides against the malaria vector Anopheles stephensi and filariasis vector Culex quinquefasciatus. The results were obtained using UV visible spectrophotometer and the images were recorded with a transmission electron microscope (TEM). The efficacy tests were then performed at different concentrations varying many hours by probit analysis. The synthesized AgNPs were spherical in shape and with varied sizes (10.47-nm leaf and 19.22-nm bark). The larvae, pupae and adults of filariasis vector C. quinquefasciatus were found to be more susceptible to our AgNPs than the malaria vector An. stephensi. The first and the second instar larvae of C. quinquefasciatus show a mortality rate of 100% after 30 min of exposure. The results against the pupa of C. quinquefasciatus were recorded as LC50 4 ppm, LC90 11 ppm and LC99 13 ppm after 3 h of exposure. In the case of adult mosquitoes, LC50 1.06 MUL/cm(2), LC90 2.13 MUL/cm(2) and LC99 2.4 MUL/cm(2) were obtained after 4 h of exposure. These results suggest that our AgNPs are environment-friendly for controlling malarial and filarial vectors. PMID- 25132569 TI - Repair of oral mucosal defects with cryopreserved human amniotic membrane grafts: prospective clinical study. AB - The aim of this study was to evaluate the clinical outcome of the surgical repair of oral mucosal defects using cryopreserved human amniotic membrane (HAM) as a graft material. Thirty-four patients with precancerous lesions such as leukoplakia, erythroplakia, and verrucous hyperplasia were included. Fresh amniotic membrane was obtained from women undergoing elective caesarean section; the membrane was cleaned, prepared in antibiotic solutions, and preserved at -80 degrees C. Results suggested that HAM promotes healing and epithelialization without specific complications. Thus we conclude that the use of HAM gives promising results in the repair of post-surgical oral mucosal defects. PMID- 25132568 TI - The metabolite profiles of the obese population are gender-dependent. AB - Studies have identified that several amino acids, in particular, branched-chain amino acids (BCAAs), have increased significantly in obese individuals when compared to lean individuals. Additionally, these metabolites were strongly associated with future diabetes, which rendered them prognostic markers suitable for obese populations. Here we report a metabonomic study that reveals new findings on the role of these amino acid markers, particularly BCAAs, in a Chinese cohort including 106 healthy obese and 105 healthy lean participants. We found that the BCAAs were correlated with insulin resistance and differentially expressed in obese men, but not in obese women. The results were verified with two independent groups of participants (Chinese, n = 105 and American, n = 72) and demonstrate that the serum metabolite profiles of the obese population are gender-dependent. The study supports the previous findings of a panel of several key metabolites as prognostic markers of the obese population and highlights the need to take into account gender differences when using these markers for risk assessment. PMID- 25132570 TI - Clinical presentation and treatment outcomes of thyroglossal duct cysts: a systematic review. AB - The aim of the present review was to analyze the main clinical signs and symptoms observed in patients with thyroglossal duct cysts (TGDCs). Secondarily we investigated the outcomes following the different types of treatment of TGDCs in children and adults. Three selected strings were run on the PubMed database to retrieve articles on these topics. A double cross-check was performed on citations and full-text articles were identified using the study inclusion and exclusion criteria. A meta-analysis was performed of the data obtained. Overall, 356 articles were identified; 24 (comprising a total of 1371 subjects) satisfied the inclusion and exclusion criteria. On the basis of the meta-analysis, the presence of a neck cystic mass was the main clinical presentation of TGDCs, with a mean rate of 75% (95% confidence interval 72-79%). The mean local wound infection rate was 4% (95% confidence interval 3-6%), this being the most frequent complication following treatment. The mean rate of overall recurrence was 11% (95% confidence interval 9-14%). The Sistrunk procedure appears to be the better choice for the therapy of TGDCs to avoid recurrences. Further studies on larger cohorts of patients regarding the minimally invasive treatment options would be helpful to elucidate and endorse their utilization in selected cases. PMID- 25132571 TI - Reply to comments on "New protocol to prevent TMJ reankylosis and potentially life threatening complications in triad patients". PMID- 25132572 TI - Facial injuries following hyena attack in rural eastern Ethiopia. AB - Hyenas are effective hunters and will consider humans as potential prey if the need and opportunity arise. This study describes the circumstances of hyena attacks, the patterns of injuries sustained, and reconstruction in a resource poor setting. As part of a charitable surgical mission to Ethiopia in 2012, 45 patients with facial deformities were reviewed, of whom four were victims of hyena attacks. A semi-structured interview was performed to ascertain the circumstances of the attack and the subsequent consequences. The age of the victims at the time of attack varied from 5 to 50 years. The attacks occurred when the victims were alone and vulnerable and took place in outdoor open spaces, during the evening or at night. The initial lunge was made to the facial area; if the jaws closed on the facial bones they were crushed, but in all cases the soft tissues were grasped and torn from the underlying bone. Reconstruction was dictated by the extent of soft tissue loss but could normally be obtained by use of local or regional flaps. Hyenas have been shown to attack humans in a predictable way and cause injuries that typically involve the soft tissues of the face. PMID- 25132573 TI - Multiple mantleomas: an unusual clinical presentation of an intriguing tumour. PMID- 25132575 TI - Modes of executive function and their coordination: introduction to the special section. PMID- 25132574 TI - Stromal microRNA-21 levels predict response to 5-fluorouracil in patients with pancreatic cancer. AB - BACKGROUND AND OBJECTIVES: MicroRNA-21 (miR-21) is upregulated and inversely associated with survival in many cancer types, including pancreatic ductal adenocarcinoma (PDAC). We studied the predictive value of miR-21 levels for gemcitabine or 5-fluorouracil (5-FU) response in tumor cells (TCs) or cancer associated fibroblasts (CAFs) in a cohort of PDAC patients from the RTOG 9704 trial. METHODS: MiR-21 expression in CAFs and TCs, determined by in situ hybridization, of the 229 PDAC subset from RTOG 9704 was correlated with (i) histopathology characteristics using a chi-square test; and (ii) patient overall survival (OS) using the Cox proportional hazards model. RESULTS: MiR-21 was strongly expressed in TCs and CAFs in 137/182 (75%) and 152/181 (84%) PDACs, respectively. MiR-21 expression in CAFs for the group given 5-FU for OS: (i) approached significance in a univariate analysis (hazard ratio [HR], 1.57; 95% confidence interval [CI], 0.95-2.57; P = 0.07); and (ii) was significant in the multivariate model (HR, 1.70; 95% CI, 1.03-2.82; P = 0.038). CONCLUSIONS: MiR-21 expression in CAFs was associated with decreased OS in PDAC patients who received 5-FU, but not gemcitabine. These findings begin to identify stromal miR-21 as a marker to guide chemotherapy choice in PDAC patients. PMID- 25132576 TI - Associations between salivary alpha-amylase and catecholamines--a multilevel modeling approach. AB - Salivary alpha-amylase (sAA) serves as indicator for sympathetic activity. However, previous findings on the association between aggregated sAA and other sympathetic markers, namely norepinephrine and epinephrine, were mixed. We therefore assumed that time-sensitive statistical analyses might help identifying possible associations of sAA and catecholamines. Data from two studies were analyzed. In Study 1, 13 men were examined in a randomized repeated within subjects double-blind study with yohimbine/placebo. In Study 2, 30 men were randomized in a repeated within-subjects design to psychosocial stress/rest. Associations of repeatedly assessed sAA, norepinephrine, and epinephrine in blood were analyzed using multilevel modeling. Over the time course, sAA was significantly associated with the catecholamines (Study 1: R(2)=.43, Study 2: R(2)=.09) and both served as mediators of sAA increases. Additional exploratory analyses suggest stronger associations during challenge/stress than during placebo/rest. These findings further support sAA as marker of sympathetic activity. PMID- 25132577 TI - Virtual reconstruction and geometric morphometrics as tools for paleopathology: a new approach to study rare developmental disorders of the skeleton. AB - Survey studies of osteoarchaeological collections occasionally yield specimens exhibiting rare skeletal developmental disorders. Beyond paleopathological diagnosis, however, it is often difficult to gain insight into the processes, mechanisms, and consequences of the pathology, notably because archaeological specimens are often fragmentary. Here, we propose a combination of virtual reconstruction (VR) and geometric morphometrics (GM) to address these issues. As an example, we use VR to reconstruct the only known archaeological specimen exhibiting persistence of the pelvic triradiate cartilage and compare it via GM with a set of healthy pelvises representing both sexes and different ontogenetic stages. Our results evidence (i) a marked deviation of the pathological pelvis from the adult mean shape, (ii) the retention of typical male features, and (iii) the retention of a paedomorphic ratio between iliac and ischiopubic size. Altogether, such data offer new insights into the modularity and integration of pelvic ontogeny, while at the same time demonstrating the usefulness of a combined VR/GM approach as complement to classical methods of paleopathology. PMID- 25132578 TI - Degenerate adaptor sequences for detecting PCR duplicates in reduced representation sequencing data improve genotype calling accuracy. AB - RAD-tag is a powerful tool for high-throughput genotyping. It relies on PCR amplification of the starting material, following enzymatic digestion and sequencing adaptor ligation. Amplification introduces duplicate reads into the data, which arise from the same template molecule and are statistically nonindependent, potentially introducing errors into genotype calling. In shotgun sequencing, data duplicates are removed by filtering reads starting at the same position in the alignment. However, restriction enzymes target specific locations within the genome, causing reads to start in the same place, and making it difficult to estimate the extent of PCR duplication. Here, we introduce a slight change to the Illumina sequencing adaptor chemistry, appending a unique four-base tag to the first index read, which allows duplicate discrimination in aligned data. This approach was validated on the Illumina MiSeq platform, using double digest libraries of ants (Wasmannia auropunctata) and yeast (Saccharomyces cerevisiae) with known genotypes, producing modest though statistically significant gains in the odds of calling a genotype accurately. More importantly, removing duplicates also corrected for strong sample-to-sample variability of genotype calling accuracy seen in the ant samples. For libraries prepared from low-input degraded museum bird samples (Mixornis gularis), which had low complexity, having been generated from relatively few starting molecules, adaptor tags show that virtually all of the genotypes were called with inflated confidence as a result of PCR duplicates. Quantification of library complexity by adaptor tagging does not significantly increase the difficulty of the overall workflow or its cost, but corrects for differences in quality between samples and permits analysis of low-input material. PMID- 25132579 TI - Investigation of sporulation in the Desulfotomaculum genus: a genomic comparison with the genera Bacillus and Clostridium. AB - The genus Desulfotomaculum, belonging to the Firmicutes, comprises strictly anaerobic and endospore-forming bacteria capable of dissimilatory sulfate reduction. These microorganisms are metabolically versatile and are widely distributed in the environment. Spore formation allows them to survive prolonged environmental stress. Information on the mechanism of sporulation in Desulfotomaculum species is scarce. Herein, this process was probed from a genomic standpoint, using the Bacillus subtilis model system as a reference and clostridial sporulation for comparison. Desulfotomaculum falls somewhere in between the Bacillus and Clostridium in terms of conservation of sporulation proteins. Furthermore, it showcased the conservation of a core regulatory cascade throughout genera, while uncovering variability in the initiation of sporulation and the structural characteristics of spores from different genera. In particular, while in Clostridium species sporulation is not initiated by a phosphorelay, Desulfotomaculum species harbour homologues of the B. subtilis proteins involved in this process. Conversely, both Clostridium and Desulfotomaculum species conserve very few B. subtilis structural proteins, particularly those found in the outer layers of the spore. Desulfotomaculum species seem to share greater similarity to the outer layers of Clostridium difficile. PMID- 25132580 TI - Pectoralis major myofascial onlay and myocutaneous flaps and pharyngocutaneous fistula in salvage laryngectomy. AB - OBJECTIVES/HYPOTHESIS: To review the fistula rate in irradiated patients undergoing salvage laryngectomy, compare the effect of closure type on fistula rate, and examine possible perioperative risk factors that might contribute to an increased fistula rate. STUDY DESIGN: Case series with chart review. METHODS: We conducted a retrospective review of the University of Pittsburgh head and neck tumor registry and identified 73 patients from 1998 to 2011 who had received prior radiation before total laryngectomy or salvage laryngectomy and who had either primary closure, pectoralis major myofascial (PMMF) flap onlay, or pectoralis major myocutaneous (PMMC) flap. RESULTS: Fistula was more common in patients who underwent initial primary closure (45%) than in patients who had immediate PMMF onlay (10.5%). The fistula rate for patients who underwent immediate PMMC flap was 28.6%, intermediate to primary closure and PMMF flap. Several factors were evaluated for relationship to fistula, but no significant associations were identified. However, patients with fistula tended to have longer inpatient stays and may have been more likely to have a history of cardiovascular or hypoxic disease. CONCLUSION: Pharyngocutaneous fistula is a well-established complication of total laryngectomy and is especially a concern in patients with a previous history of radiation. Our retrospective review demonstrates that PMMF onlay flap appears to be more effective in reducing the rate of fistula compared to primary closure in these patients. Myocutaneous augmentation flaps, in contrast, have a fairly high fistula rate and may be better replaced with alternative closures such as free flaps. LEVEL OF EVIDENCE: 4. PMID- 25132581 TI - Abnormalities in renal tubular phosphate handling in children with sickle cell disease. AB - BACKGROUND: The mechanisms responsible for the hyperphosphatemia in patients with sickle cell disease (SCD) and preserved glomerular filtration rate (GFR) are not fully understood. The role of fibroblast growth factor 23 (FGF23), a phosphaturic hormone has not been investigated in SCD. Hence, we evaluated parameters of renal tubular phosphorus handling and their relation to prevailing FGF23 levels in a cohort of young SCD patients. METHODS: Renal tubular phosphate handling and circulating levels of various analytes including FGF23 and parathyroid hormone (PTH) were measured in 24 children with SCD and normal estimated GFR in a cross sectional study. Correlation and regression analysis were employed to derive relationships between serum phosphorus and several variables. RESULTS: Most children showed elevated age- adjusted serum phosphorus (5.1 +/- 0.7 mg/dl) levels. Tubular re-absorption of phosphorus(TRP) (96.3 +/- 2.1%) and tubular maximum re-absorption of phosphorus per unit volume of GFR (TMP/GFR) (4.9 +/- 0.6 mg/dl) were both elevated. Plasma intact FGF23 concentrations were elevated (81 +/- 38 pg/ml) while the average PTH values were normal in most patients (50 +/- 27 pg/ml). Univariate analysis showed significant correlations of serum phosphorus with TMP/GFR, alkaline phosphatase, age, lactate dehydrogenase (LDH), and log intact FGF23. TMP/GFR correlated with log intact FGF23 (r = 0.5, P< or = 0.01) but not with PTH. Multiple regression analysis yielded an independent relationship of serum phosphorus with TMP/GFR. CONCLUSION: The elevated serum phosphorus concentrations with simultaneously increased TMP/GFR and elevated FGF23 levels collectively suggest that patients with SCD display proximal tubular resistance to the action of FGF23 before any decline in GFR. PMID- 25132583 TI - Incidence and dynamics of active cytomegalovirus infection in allogeneic stem cell transplant patients according to single nucleotide polymorphisms in donor and recipient CCR5, MCP-1, IL-10, and TLR9 genes. AB - Single nucleotide polymorphisms (SNPs) in genes involved in the activation or regulation of innate and adaptive immune responses may modulate the susceptibility to and the natural history of certain chronic viral infections. The current study aimed to investigate whether donor and recipient SNPs in the chemokine receptor 5 (rs1800023), monocyte chemoattractant protein 1 (rs13900), interleukin-10 (rs1878672), and Toll-like receptor 9 (rs352140) genes would exert any influence on the rate of incidence and features of CMV DNAemia in the allogeneic stem cell transplantation setting. This was a retrospective observational multicenter study. The cohort consisted of 102 non-consecutive allogeneic stem cell transplant recipients. SNP genotyping was performed by allele-specific real-time PCR. CMV surveillance was performed by the pp65 antigenemia assay/and or by real-time PCR. Seventy-three patients developed CMV DNAemia within the first 100 days after transplantation (71.5%). Neither donor nor recipient SNPs were associated significantly with the rate of incidence of active CMV infection, nor with the need for pre-emptive antiviral therapy. Both the duration of CMV DNAemia and the plasma CMV DNA peak load during episodes were significantly higher in patients harboring the donor (but not the recipient) chemokine receptor 5 A/A genotype, than in their A/G and G/G counterparts (P = 0.022 and P = 0.045, respectively). The data reported suggest that SNPs in chemokine receptor 5 may influence the dynamics of CMV infection in the Allo-SCT setting. PMID- 25132585 TI - Gene expression profiling of lung myofibroblasts reveals the anti-fibrotic effects of cyclosporine. AB - Cyclosporine, a calcineurin inhibitor, is a potent immunosuppressive agent that acts chiefly through the inactivation of T-lymphocytes. Several clinical studies have demonstrated the effectiveness of cyclosporine for treating fibrotic lung disease, but the underlying mechanism remains elusive. We hypothesized that cyclosporine exerts direct effects against fibrogenesis of lung myofibroblasts, and aimed to elucidate the mechanism of this anti-fibrotic effect through gene expression profiling using DNA microarray analysis. We found that cyclosporine suppressed the expression of alpha-smooth muscle actin and collagen type I in myofibroblasts that had been differentiated from a fetal human lung fibroblast cell line by induction with transforming growth factor (TGF)-beta. Furthermore, microarray analysis revealed that cyclosporine down-regulated 57 genes whose expression levels were increased by TGF-beta, and up-regulated 73 genes, whose expression was decreased by TGF-beta. Classifying these 57 down-regulated and 73 up-regulated genes with the Database for Annotation, Visualization and Integrated Discovery (DAVID) web tool, we have identified the involvement of several functional categories, including innate immunity, cytokine interaction, growth factor, and cancer pathway. Of the identified genes, we selected three fibrosis related genes, insulin-like growth factor binding protein 2 (IGFBP2), inhibitor of DNA binding 1 (ID1) and peroxisome proliferator-activated receptor gamma (PPARG), and validated their expression patterns by quantitative reverse transcription-polymerase chain reaction. Cyclosporine treatment decreased the expression levels of IGFBP2 and ID1, but increased PPARG expression. These results suggest that cyclosporine is a potent anti-fibrotic agent acting on myofibroblasts. Therefore, cyclosporine shows potential as a novel remedy for fibrotic lung disease. PMID- 25132582 TI - Pancreatic stem cells remain unresolved. AB - Diabetes mellitus is caused by absolute (type 1) or relative (type 2) deficiency of insulin-secreting islet beta cells. An ideal treatment of diabetes would, therefore, be to replace the lost or deficient beta cells, by transplantation of donated islets or differentiated endocrine cells or by regeneration of endogenous islet cells. Due to their ability of unlimited proliferation and differentiation into all functional lineages in our body, including beta cells, embryonic stem cells and induced pluripotent stem cells are ideally placed as cell sources for a diabetic transplantation therapy. Unfortunately, the inability to generate functional differentiated islet cells from pluripotent stem cells and the poor availability of donor islets have severely restricted the broad clinical use of the replacement therapy. Therefore, endogenous sources that can be directed to becoming insulin-secreting cells are actively sought after. In particular, any cell types in the developing or adult pancreas that may act as pancreatic stem cells (PSC) would provide an alternative renewable source for endogenous regeneration. In this review, we will summarize the latest progress and knowledge of such PSC, and discuss ways that facilitate the future development of this often controversial, but crucial research. PMID- 25132586 TI - Assessment of the relationship between transepidermal water loss (TEWL) and severity of clinical signs (CADESI-03) in atopic dogs. AB - BACKGROUND: Atopic dermatitis (AD) is a common allergic skin disease of dogs. Objective documentation of disease severity is important for the assessment of responses to therapeutic interventions. One common means of assessing the severity of clinical signs is the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03. In addition, studies of the biophysical parameters of the skin suggest that assessment of transepidermal water loss (TEWL) may also have value for estimation of disease severity. HYPOTHESIS/OBJECTIVES: The aim of the present study was to verify the correlation between TEWL and CADESI-03 measured at 10 different body sites. ANIMALS: Twenty-six dogs with AD (age range 1-7 years, median age 3 years). METHODS: The assessment was performed at the following 10 body sites: the lumbar, inguinal, ventral abdominal, interdigital regions, axillary fossa, lateral thorax, lateral aspect of the antebrachium, concave surface of the auricle, cheek and bridge of the nose. RESULTS: Positive correlations were found between TEWL and the total CADESI-03 for the auricle (r = 0.59), bridge of nose (r = 0.62) and interdigital skin (r = 0.47). Positive correlations were also observed between TEWL and local CADESI-03 scores for the axillary fossa (r = 0.73), inguinal region (r = 0.55) and interdigital skin (r = 0.77). CONCLUSIONS AND CLINICAL IMPORTANCE: The results indicate that it may be possible to use measurement of TEWL to assess the severity of skin lesions, but a positive correlation was found in only five of 10 body regions examined. PMID- 25132587 TI - Construction of recombinant adenovirus vector containing hBMP2 and hVEGF165 genes and its expression in rabbit Bone marrow mesenchymal stem cells. AB - To construct an adenovirus vector co-expressing human bone morphogenetic protein (hBMP2) and human vascular endothelial growth factor (hVEGF165) as well as green fluorescence protein (GFP) as a marker, with which the intracellular expression of the inserted genes could be identified in Bone marrow mesenchymal stem cells (BM-MSCs). BMP2 and VEGF165 genes were PCR amplified from a cDNA library and inserted to the polyclonal site of adenovirus shuttle plasmid pAd-MCMV-GFP. The virus solution (Ad-BMP2-VEGF165) was generated by co-transfecting HEK293 cells with the constructed recombinant shuttle plasmid pAd-MCMV-BMP2-VEGF165 and adenovirus helper plasmid pBHGloxDelta (delta) E1, 3Cre. The virus solution was further purified and virus titer was determined accordingly. The expression of the target genes was subsequently detected and quantified in rabbit BM-MSCs by using real time PCR, ELISA and Western blotting. The recombinant adenovirus vector containing BMP2 and VEGF165 (Ad-BMP2-VEGF165) was successfully constructed, which was confirmed by Sanger sequencing, colony PCR, as well as visually detection of GFP, and the titer of the adenovirus was 1*10(10)PFU/mL, and the proteins level of BMP2 and VEGF165 secreted in the supernatant are significantly higher than the control. Recombinant adenovirus vector containing hBMP2 and hVEGF165 genes was successfully constructed. The transfection rate of BM-MSCs by the adenovirus was high (95% at 100 MOI) and the BMP2 and VEGF165 genes was highly expressed in the cells. The present study provides a method to efficiently express the target genes in BM-MSCs and an vector for further research of bone defect repair using dual genes of BMP2 and VEGF165. PMID- 25132589 TI - [The role of the psychiatrist in the new mental health care]. PMID- 25132588 TI - A randomized trial comparing dual axis rotational versus conventional coronary angiography in a population with a high prevalence of coronary artery disease. AB - OBJECTIVES: To compare the safety, radiation dose, and contrast volume between dual axis rotational coronary angiography (DARCA) and conventional coronary angiography (CCA). BACKGROUND: CCA is performed in multiple, predefined stationary views, at different angulations around the patient, for both the left and right coronary arteries. DARCA (AlluraXperSwingTM, Philips, the Netherlands) involves a pre-set rotation of the C-arm around the patient and allows for the visualization of each coronary artery in different views, using a single automatic pump contrast injection. METHODS: From November 2012 to February 2013, 201 patients were randomly assigned to either CCA (n = 100) or DARCA (n = 101). Exclusion criteria included acute coronary syndrome (ACS), prior PCI or CABG. CCAs were performed in 4 acquisition runs for the left coronary artery and 2 to 3 acquisition runs for the right coronary artery, whereas DARCAs were performed in a single run for each coronary artery. RESULTS: Baseline demographics and clinical characteristics were similar for both groups. The overall prevalence of CAD was 77.6%. The DARCA group had a significant reduction in the amount of contrast, 60 ml (IQR: 52.5-71.5 ml) versus 76 ml (IQR: 68-87 ml), P < 0.0001; and radiation dose by Air Kerma, 269.5 mGy (IQR: 176-450.5) versus 542.1 mGy (IQR: 370.7-720.8), P < 0.0001. There were fewer patients requiring additional projections in the DARCA group: 54.0% versus 75.0%; P = 0.002. CONCLUSIONS: In a population with a high prevalence of CAD, DARCA was safe and resulted in a significant decrease in contrast volume and radiation dose. PMID- 25132591 TI - [The working alliance in inpatient treatment for personality disorders and its connection with patient characteristics: an exploratory study]. AB - BACKGROUND: The working alliance between therapist and patient has been investigated frequently, but much less is known about the working alliance in specific patient groups in specific settings. AIM: To obtain insight into the characteristics of the working alliance in intensive inpatient psychotherapy involving patients with severe personality disorders, and to pay special attention to patient characteristics such as diagnosis and attachment. METHOD: At the end of the first phase of treatment we collected, on the basis of questionnaires, information about the working alliance and attachment of 60 patients with a severe personality disorders who had received inpatient psychotherapy. RESULTS: Working alliances with therapist and team were found to be weaker than in outpatient populations; working alliances with the therapist proved to be stronger than working alliances with the treatment team. Cluster C patients developed a better working alliance with the treatment team than did cluster B patients, particularly in the domain of treatment goals. Patients in this study turned out to be attached more anxiously and 'avoidantly' than patients in general outpatient populations; no correlation was found between patients' attachment and the strength of the working alliance. However, when a distinction was made between patients with extreme scores and patients with average scores, results showed that the more anxiously patients felt attached, the higher were their scores for their working alliance with the treatment team. CONCLUSION: It is more difficult to establish a working alliance with patients who have a severe personality disorder than with patients suffering from a less severe personality disorder. Patients with a severe personality disorder seemed to show a higher degree of anxious attachment and to have a more critical attitude to the working alliance. PMID- 25132592 TI - [Body dysmorphic disorder in cosmetic surgery - prevalence, psychiatric comorbidity and outcome]. AB - BACKGROUND: Patients suffering from body dysmorphic disorder (bdd) are preoccupied with a slight or imagined defect in appearance. AIM: First of all, to review the literature on the prevalence of bdd in cosmetic surgery and thereafter to review the literature on psychiatric comorbidity and the outcome of surgical interventions. METHOD: We based our search strategy on Embase, Medline and PubMed, using the search terms 'body dysmorphic disorder', 'cosmetic surgery', 'prevalence', 'comorbidity' and 'outcome'. Our search covered English and Dutch literature published after the introduction of bdd in dsm-iii-r and before 1 November, 2013. A study of the relevant articles enabled us to access additional articles mentioned in these texts. RESULTS: Our initial search strategy turned out to be too narrow. It was therefore broadened to include 'body dysmorphic disorder', 'cosmetic surgery', and 'prevalence'. Eventually we included 23 original articles. In 11 of these the prevalence of bdd varied from 3.2 to 53.6%. Twelve articles on psychiatric comorbidity revealed predominantly mood and anxiety disorders on axis I and cluster C personality disorders on axis II. Only two studies reported on the outcome of cosmetic surgery performed on bdd patients; surgical interventions, however, seemed to result in new preoccupations with the prolongation of psychiatric comorbidity. CONCLUSION: bdd is a common psychiatric disorder that can sometimes lead to cosmetic surgery. However, pre operative screening of bdd patients is vital so that efficient psychiatric treatment can be initiated and patients are not subjected to surgical interventions which may be ineffective or even harmful. PMID- 25132594 TI - [Diagnosis should not be confused with classification in psychiatry]. PMID- 25132593 TI - [Should diagnosis and classification be kept separate in psychiatry?]. AB - BACKGROUND: In medicine it is common practice to diagnose patients before classifying their symptoms. In psychiatry, however, the two procedures cannot be kept separate; they overlap and are interlinked. AIM: To discuss relevant classification systems and the relationship between diagnosis and classification and to find out what kind of relationship is the best one for psychiatry. METHOD: The literature was searched and a conceptual analysis was performed on the basis of relevant literature, manuals and principles formulated by psychiatrists. RESULTS: It is argued that deliberation, an important part of the diagnostic process, can only play a significant role if diagnosis and symptom classification are kept completely separate. In this process of deliberation there should be a role for clinical phenomena such as improvement of symptoms, worsening of symptoms, objectification and reification, and psychiatrists should have the opportunity to consider whether these aspects really belong to the field of psychiatry. CONCLUSION: In psychiatry the relationship between diagnosis and symptom classification is not clear-cut. However, since deliberation plays a major role in psychiatric diagnosis, it is important that psychiatrists continue to keep diagnosis separate from symptom classification. Unlike other medical specialists, psychiatrists sometimes classify an illness before making a diagnosis. Existing guidelines and an all-embracing guideline regarding diagnosis need to be harmonised. Confusion and misdiagnosis could be reduced if classifications from two classification systems were to be included in medico psychiatric diagnosis. PMID- 25132595 TI - [Good clinical practice and the maintenance of ethical standards in medical research: advice for junior researchers working in mental health care]. AB - BACKGROUND: In mental health care, more and more research is being done, particularly in the field of educational programmes. Unfortunately, junior researchers are often not fully informed about the rules and regulations relating to research and about medical ethics. Therefore, they are not in a position to make considered judgements that conform to good clinical practice and acceptable medical ethics.
AIM: To give practical advice to trainees, stimulating them to think carefully about ethical standards in patient-related research in mental health care. METHODS The article provides a practice-based overview of practical advice and ethical considerations.
RESULTS: We stress that before beginning their research, researchers should think very carefully about the ethics of medical research. Instructions and guidelines relating to medical and ethical standards are to be found in: directive for good clinical practice compiled by the central committee for human research (CCMO) with the accompanying e-learning module and in the basic course 'rules and organisation for clinical researchers' (BROK). Practical tips, illustrated with examples, provide a framework for stimulating thoughts on medical ethics. Finally, it is important to improve the ways in which research is embedded in the organisational structure of teaching programmes.
CONCLUSION: Basic information about GCP and the upholding of medical and ethical standards in patient-related research can be obtained from various sources. The main challenge is to ensure that GCP is firmly embedded in patient-related research undertaken by junior researchers. PMID- 25132596 TI - [Cryptococcal meningitis and neuropsychiatric consequences of HIV-infection]. AB - A 49-year-old African-born male was admitted to hospital with an acute psychosis. He had been treated by an internist after being found to have hiv; as a result of non-compliance over a period of about four months his cd4-count had dropped to 40. Six months earlier he had developed a cryptococcal meningitis, which left him a number of neurological and psychiatric symptoms. During his stay in hospital there had to be good collaboration with the specialist in internal medicine whose dual task was to manage the patient's dramatically low cd4-account as well as his psychosis. Cryptococcal meningitis is a risk factor for psychiatric disorders and mortality in hiv-infected persons. PMID- 25132597 TI - [Reaction on 'Contribution to quality of care or caught in a digital labyrinth? Experience with electronic records of patients receiving long-term mental health care' (1)]. PMID- 25132598 TI - [Reaction on 'Minocycline for schizophrenia: a brief overview']. PMID- 25132599 TI - Suppression of TDO-mediated tryptophan catabolism in glioblastoma cells by a steroid-responsive FKBP52-dependent pathway. AB - Tryptophan catabolism is increasingly recognized as a key and druggable molecular mechanism active in cancer, immune, and glioneural cells and involved in the modulation of antitumor immunity, autoimmunity and glioneural function. In addition to the pivotal rate limiting enzyme indoleamine-2,3-dioxygenase, expression of tryptophan-2,3-dioxygenase (TDO) has recently been described as an alternative pathway responsible for constitutive tryptophan degradation in malignant gliomas and other types of cancer. In addition, TDO has been implicated as a key regulator of neurotoxicity involved in neurodegenerative diseases and ageing. The pathways regulating TDO expression, however, are largely unknown. Here, a siRNA-based transcription factor profiling in human glioblastoma cells revealed that the expression of human TDO is suppressed by endogenous glucocorticoid signaling. Similarly, treatment of glioblastoma cells with the synthetic glucocorticoid dexamethasone led to a reduction of TDO expression and activity in vitro and in vivo. TDO inhibition was dependent on the immunophilin FKBP52, whose FK1 domain physically interacted with the glucocorticoid receptor as demonstrated by bimolecular fluorescence complementation and in situ proximity ligation assays. Accordingly, gene expression profile analyses revealed negative correlation of FKBP52 and TDO in glial and neural tumors and in normal brain. Knockdown of FKBP52 and treatment with the FK-binding immunosuppressant FK506 enhanced TDO expression and activity in glioblastoma cells. In summary, we identify a novel steroid-responsive FKBP52-dependent pathway suppressing the expression and activity of TDO, a central and rate-limiting enzyme in tryptophan metabolism, in human gliomas. PMID- 25132600 TI - The inhibition effects of insulin on BMP2-induced muscle heterotopic ossification. AB - Bone morphogenetic proteins (BMPs) play an important role in regulating osteoblastic differentiation and bone formation. But the diffuse of BMPs into muscle tissues around bone injury sites often leads to heterotopic ossification, which has been regarded as one of major side-effects of BMP implementation in bone defect patients. It raises great demands for exploring effective methods that preventing BMP-induced heterotopic ossification while not interrupting the osteoinductive activity of BMPs for in situ bone defect repair. Here we found insulin, a positive regulator for bone regeneration, inhibited BMP2-induced muscle heterotopic ossification by suppressing the expression of bone transcription factor Osterix. By analyzing downstream molecules of insulin pathway, we found AKT/mTOR/GSK3 signaling was responsible for the inhibition of insulin on BMP2-induced ossification, and GSK3 inhibitor SB216763 attenuated BMP2 induced muscle heterotopic ossification. The data might shed light on developing effective clinical therapy for inhibiting muscle heterotopic ossification when BMPs were used bone defect repair. PMID- 25132601 TI - Nanovesicles engineered from ES cells for enhanced cell proliferation. AB - Extracellular vesicles (Exosomes and microvesicles) have drawn wide attentions in both diagnostic and therapeutic applications, since they are considered to shuttle biological signals intercellularly. However, further research on exosomes is limited by their rarity and heterogeneity even after lengthy isolation processes. In particular, these limitations are challenging in therapeutic applications. To meet these demands, cell-derived nanovesicles that mimic exosomes were generated by extruding living embryonic stem cells through micro filters. These nanovesicles have an enclosed lipid bilayer and contain cellular contents. The present study investigated the ability of these nanovesicles to improve proliferation by treating primary murine skin fibroblasts with the nanovesicles. The treated skin fibroblasts showed higher expression levels of mRNA, VEGF-alpha, protein levels of TGF-beta collagen I, PCNA, and Ki-67, as well as enhanced cell proliferation rate and number, compared to non-treated cells. The results indicate that treatment with the nanovesicles could potentially contribute to recovery or wound healing process of tissues. PMID- 25132603 TI - Carbon nanodots featuring efficient FRET for two-photon photodynamic cancer therapy with a low fs laser power density. AB - The 5,10,15,20-tetrakis(1-methyl 4-pyridinio) porphyrins (TMPyP), a photosensitizer used for photodynamic therapy of cancers (PDT), were linked to carbon dots (CDots) to form the conjugates of CDot-TMPyP by the electrostatic force. The 415 nm emission band of CDots was well overlapped with the absorption band of TMPyP, so that the Cdots in conjugates can work as donor to transfer the energy to TMPyP moiety by fluorescence resonance energy transfer (FRET) with an FRET efficiency of 45%, determined by the fluorescence lifetime change between the free CDots and conjugated CDots. The two-photon absorption cross section (TPACS) of TMPyP is as low as 110 GM and the TMPyP thus be not suitable for two photon PDT. Whereas the CDots have high TPACS, and their TPACS are excitation wavelength dependent with the maximum value of 15000 GM at 700 nm. Therefore, the conjugates of CDot-TMPyP were explored for two-photon excitation (TPE) PDT. The two-photon image of CDot-TMPyP in Hela cells was clearly seen under the excitation of a 700 nm femto-second (fs) laser. The singlet oxygen production of CDot-TMPyP was also much higher than that of TMPyP alone under TPE of a 700 nm fs laser. The in vitro PDT killing was further achieved with CDot-TMPyP by TPE of the 700 nm fs laser. Particularly herein the low power density of fs laser from unfocused laser beam was successfully used to carry out the TPE PDT, because of the high TPACS of CDots. These results demonstrate that the CDot-TMPyP conjugates are promising for TPE PDT and needed to investigate further. PMID- 25132602 TI - Nucleotide biosynthesis arrest by silencing SHMT1 function via vitamin B6-coupled vector and effects on tumor growth inhibition. AB - Serine hydroxymethyltransferase isoforms (SHMT1 & SHMT2alpha), which serve as scaffold protein for the formation of a multi-enzyme complex and generate one carbon unit for the de novo thymidylate biosynthesis pathway during DNA synthesis, are vitamin B6 (VB6)-dependent enzyme. Cancer cells with high proliferation intensity need increased SHMT activation which enforces the facilitated-diffusion of VB6 for the continuous functioning of thymidylate synthase cycle. Therefore, SHMT knockdown presents an alternative approach to prevent DNA synthesis in cancer cells; however, its potential to inhibit cancer growth remains unknown so far. Here we demonstrated that VB6 coupled to poly(ester amine) (VBPEA) enforces a high level of VTC (VB6-transporting membrane carriers)-mediated endocytosis of the complexed SHMT1 siRNA (siSHMT1) to interrupt the thymidylate biosynthesis pathway of cancer cells. The detrimental effect of SHMT1 knockdown on the disintegration of multi-enzyme complex resulted in cell cycle arrest and a decrease in cell's genomic DNA content, leading to enhanced apoptotic events in cancer cells. A reduction in tumor size was observed with constant SHMT1 suppression in xenograft mice. This study illustrates how silencing the SHMT1 expression inhibits cancer growth and the increased VB6 channeling for sustenance of cancer cells promotes VB6-coupled vector to elicit enhanced delivery of siSHMT1. PMID- 25132604 TI - A microwell pattern for C17.2 cell aggregate formation with concave cylindrical surface induced cell peeling. AB - We have developed a polydimethylsiloxane (PDMS) pattern with arrays of microwells for the formation of multicellular aggregates by C17.2 neural stem cells. Upon interfacing with the patterns, the neural stem cells would firstly attach to the microwell sidewalls, forming cellular strips on day 1 after plating. For channel connected microwells, cellular strips on the concave semi-cylindrical sidewall surfaces continued among wells and through channels, followed by strip peeling due to prestress arising from actin filaments and assembly of suspending cellular aggregates within the microwells in the following 1-2 days. Our results also suggested that a small microwell diameter of 80 and 100 MUm and a narrow channel width of 20 MUm would facilitate the aggregate formation among the structural dimensions tested. Finite element method (FEM) simulation revealed that cellular strips on the semi-cylindrical sidewall surfaces peeled under significantly smaller prestresses (critical peeling prestress, CPP), than cells on flat substrates. However, the CPP by itself failed to fully account for the difference in aggregate inducing capability among the patterns addressed, suggesting cell growth behaviors might play a role. This study thus justified the current patterning method as a unique and practical approach for establishing 3D neural stem cell-based assay platforms. PMID- 25132605 TI - Enhanced angiogenic effect of adipose-derived stromal cell spheroid with low level light therapy in hind limb ischemia mice. AB - The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on transplanted human adipose-derived mesenchymal stem cells (hASCs) spheroid in a hind limb ischemia animal model. LLLT, hASCs spheroid and hASCs spheroid transplantation with LLLT (spheroid + LLLT) were applied to the ischemic hind limbs in athymic mice. The survival, differentiation and secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), and hepatocyte growth factor (HGF) of the spheroid ASCs were evaluated by immunohistochemistry and western blots. Spheroid + LLLT group had enhanced the tissue regeneration, including angiogenesis, compared with the ASC group. The spheroid ASCs contributed to tissue regeneration via differentiation and secretion of growth factors. In the spheroid + LLLT group, the survival of spheroid hASCs increased with a concomitant decrease in apoptosis of spheroid hASCs in the ischemic hind limb. The secretion of growth factors was stimulated in the spheroid + LLLT group compared with the ASCs and spheroid group. These data suggested that LLLT is an effective biostimulator of spheroid hASCs in tissue regeneration that enhanced the survival of ASCs and stimulated the secretion of growth factors in the ischemic hind limb. PMID- 25132606 TI - An albumin-based theranostic nano-agent for dual-modal imaging guided photothermal therapy to inhibit lymphatic metastasis of cancer post surgery. AB - A large variety of cancers are associated with a high incidence of lymph node metastasis, which leads to a high risk of cancer death. Herein, we demonstrate that multimodal imaging guided photothermal therapy can inhibit tumor metastasis after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA), which is covalently linked with diethylenetriamine pentaacetic acid (DTPA) molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits strong fluorescence together with high near-infrared (NIR) absorbance, and in the mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging. In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after being injected into the primary tumor would quickly migrate into tumor-associated SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd IR825, SLNs with metastatic cancer cells can be effectively ablated under exposure to a NIR laser. Such treatment when combined with surgery to remove the primary tumor offers remarkable therapeutic outcomes in greatly inhibiting further metastatic spread of cancer cells and prolonging animal survival. Our work presents an albumin-based theranostic nano-probe with functions of multimodal imaging and photothermal therapy, together with a 'photothermal ablation assisted surgery' strategy, promising for future clinical cancer treatment. PMID- 25132607 TI - PAIN OUT: the making of an international acute pain registry. AB - BACKGROUND: About 240 million patients undergo surgery every year, worldwide. Roughly 50% of these patients report clinically significant pain. Numerous barriers impede provision of adequate management. Lack of evidence about appropriateness and effectiveness of interventions is one. A registry can provide such information, eventually facilitating better management. This paper reports the development and feasibility of PAIN OUT, the first international acute pain registry, established with funds from the European Commission, and presents preliminary analysis to illustrate the nature of investigations that registry data make possible. METHODS: On the first postoperative day, 6347 adult patients undergoing orthopaedic or general surgery, in 11 medical centres in Europe and Israel, provided Patient Reported Outcomes (PROs) using a validated questionnaire. Clinical data were abstracted from the patient's chart. RESULTS: Feasibility worked well. Over a period of 1 year, surveyors accrued targeted data sets and entered them into an online browser. Collaborators could receive online feedback comparing their findings about PROs against anonymized findings from other centres. Missing data for the majority of variables were low. Despite considerable variability between institutions, a large number of patients were treated according to the generic, evidence-based recommendations we assessed. However, this was not sufficient to result in acceptable outcomes for the majority of patients. CONCLUSION: The initial development of PAIN OUT has been achieved. From 2013, it continues as a not-for-profit academic project, open to clinicians and researchers worldwide. The International Association for Study of Pain and PAIN OUT will work together to maintain, disseminate and develop the registry. PMID- 25132608 TI - Effects of different sleep deprivation protocols on sleep perception in healthy volunteers. AB - OBJECTIVES: To investigate whether different protocols of sleep deprivation modify sleep perception. METHODS: The effects of total sleep deprivation (TD) and selective rapid eye movement (REM) sleep deprivation (RD) on sleep perception were analyzed in normal volunteers. Thirty-one healthy males with normal sleep were randomized to one of three conditions: (i) normal uninterrupted sleep; (ii) four nights of RD; or (iii) two nights of TD. Morning perception of total sleep time was evaluated for each condition. Sleep perception was estimated using total sleep time (in hours) as perceived by the volunteer divided by the total sleep time (in hours) measured by polysomnography (PSG). The final value of this calculation was defined as the perception index (PI). RESULTS: There were no significant differences among the three groups of volunteers in the total sleep time measured by PSG or in the perception of total sleep time at baseline condition. Volunteers submitted to RD exhibited lower sleep PI scores as compared with controls during the sleep deprivation period (P <0.05). Both RD and TD groups showed PI similar to controls during the recovery period. CONCLUSION: Selective REM sleep deprivation reduced the ability of healthy young volunteers to perceive their total sleep time when compared with time measured by PSG. The data reinforce the influence of sleep deprivation on sleep perception. PMID- 25132609 TI - WITHDRAWN: Sleep quality changes in chronically depressed patients treated with mindfulness-based cognitive therapy or cognitive behavioral analysis system for psychotherapy: a pilot study. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 25132610 TI - Sleep architecture in infants with spinal muscular atrophy type 1. AB - OBJECTIVE: Few reports on sleep patterns of patients with spinal muscular atrophy type 1 (SMA1) have been published and none on sleep microstructure. The aim of this study was to analyze sleep architecture and microstructure in a group of infants with SMA1, compared with age- and sex-matched controls. METHODS: Twelve SMA1 patients (six males, mean age 5.9 months) and 10 controls (five males, mean age 4.8 months) underwent full polysomnography to evaluate their sleep architecture and microstructure by means of the cyclic alternating pattern (CAP). RESULTS: Compared with control children, SMA1 patients showed increased sleep latency and apnea/hypopnea index. CAP analysis revealed a significant increase in the percentage of A1 CAP subtypes, a reduction of that of A3 subtypes and of A2 and A3 indexes (number/h), indicating a dysfunction of the arousal system in these patients. CONCLUSION: The results indicate the presence of an abnormality of sleep microstructure in SMA1 patients, characterized by a reduction of A2 and A3 CAP subtypes. We hypothesize that SMA1 patients have reduced arousability during non-rapid eye movement sleep, which could be interpreted as additional evidence of central nervous system involvement in this disease. PMID- 25132613 TI - Letter to the editor. PMID- 25132614 TI - Letter to the editor. PMID- 25132615 TI - Author response. PMID- 25132616 TI - Picking up myelodysplastic syndromes and megaloblastic anemias on peripheral blood: use of NEUT-X and NEUT-Y in guiding smear reviews. PMID- 25132617 TI - Scarless outpatient ablation of pilonidal sinus: a pilot study of a new minimally invasive treatment. AB - Pain and secretion of purulent materials are symptoms that are often associated with the pilonidal sinus. Generally, these symptoms are neglected by patients for a long time. Patients seek medical attention too late, fearing a prolonged period of pain and inability after surgery. The optimal therapy for pilonidal sinus should have the following characteristics: high healing rate, low recurrence rate, minimal postoperative pain and low cost. The aim of this study is to explore the effectiveness and safety of a new minimally invasive treatment: the scarless outpatient ablation of pilonidal sinus (SOAP). A total of 31 consecutive patients were enrolled; 27 of 31 patients were declared healed after the surgery (87.09%). After 1 year, only 4 of 27 patients (14.81%) reported symptoms related to recurrence of the disease. The average duration of the operation was 7.47 minutes. Patients reported the disappearance of painful symptoms after approximately 2.62 days and had been away from work for 0.53 days. No complications were recorded during the period of study. The advantages of the procedure examined in this study are its simplicity and rapidity of execution, its outpatient setting, its low cost and lack of complications. In our opinion, a randomised controlled trial should be conducted to validate the results related to this technique. PMID- 25132618 TI - Is metformin ready for prime time in pregnancy? Probably not yet. AB - Metformin is one of the most commonly used drugs to treat type 2 diabetes and is safe and effective. Its main mechanism of action is thought to be the activation of AMP-activated protein kinase (AMPK) via inhibition of mitochondrial ATP generation. Recent use of metformin as an 'insulin sensitizer' in women with polycystic ovarian syndrome to increase fertility has been successful and resulted in the chance observation that continued use during pregnancy appeared to be safe. There are few studies of metformin in animal models of diabetic pregnancy. However, some data have implicated fetal AMPK activation in neural tube defects. While a recent report suggests that metformin may not activate fetal AMPK, which is reassuring, studies in pregnant woman with gestational diabetes and type 2 diabetes, which are ongoing, require completion before we can conclude that its use in pregnancy is safe. Furthermore, follow-up of the offspring will be critical to determine whether such treatment decreases or increases the development of obesity and diabetes. PMID- 25132619 TI - Outcomes of haematology/oncology patients admitted to intensive care unit at The Canberra Hospital. AB - BACKGROUND: Outcomes for haematology/oncology patients have improved; however, determining their suitability for intensive care unit (ICU) admission remains challenging and controversial. AIM: Examine outcomes of patients admitted to an Australian tertiary hospital ICU and explore potential prognostic factors. METHODS: A retrospective review of patients with haematological and solid tumour malignancies non-electively admitted to The Canberra Hospital (TCH) ICU, between January 2008 and December 2012. Patient demographics, cancer details, reasons for ICU admission and Acute Physiologic and Chronic Health Evaluation (APACHE) II scores were collected, and survival rates calculated and correlated with potential prognostic factors. RESULTS: Of 205 patients, 113 (55%) had haematological malignancies, and 92 (45%) had solid tumours: 58% male and mean age 60.3 years (standard deviation (SD) 13.4). Eighty-two per cent of solid tumour patients had metastatic disease and 55% received palliative chemotherapy. Primary reasons for ICU admission included sepsis (59%), respiratory distress (37%) and hypotension/shock (18%). Mean APACHE II score was 20.1(SD 0.55); mean length of stay in ICU, 4 days (SD 5.2); ICU survival was 76% with 62% and 41% alive at 30 days and 6 months respectively. Overall 1-year survival was 36%. High APACHE II scores and >=2 organs failing were significant risk factors for 30-day mortality. CONCLUSION: Short-term outcomes were similar to contemporary studies from a general tertiary hospital setting and better than historical data. Sixty two per cent of patients were alive 30 days post-ICU admission, with a significant minority alive at 12 months, confirming some patients achieved worthwhile outcomes. Further research is needed to ensure appropriate patient selection and to explore quality of life post ICU. PMID- 25132620 TI - In vivo 1H MRS of human gallbladder bile at 3 T in one and two dimensions: detection and quantification of major biliary lipids. AB - In vitro (1)H MRS of human bile has shown potential in the diagnosis of various hepatopancreatobiliary (HPB) diseases. Previously, in vivo (1)H MRS of human bile in gallbladder using a 1.5 T scanner demonstrated the possibility of quantification of choline-containing phospholipids (chol-PLs). However, other lipid components such as bile acids play an important role in the pathophysiology of the HPB system. We have employed a higher magnetic field strength (3 T), and a custom-built receive array coil, to improve the quality of in vivo (1)H MRS of human bile in the gallbladder. We obtained significant improvement in the quality of 1D spectra (17 healthy volunteers) using a respiratory-gated PRESS sequence with well distinguished signals for total bile acids (TBAs) plus cholesterol resonating at 0.66 ppm, taurine-conjugated bile acids (TCBAs) at 3.08 ppm, chol PLs at 3.22 ppm, glycine-conjugated bile acids (GCBAs) at 3.74 ppm, and the amide proton (-NH) arising from GCBAs and TCBAs in the region 7.76-8.05 ppm. The peak areas of these signals were measured by deconvolution, and subsequently the molar concentrations of metabolites were estimated with good accuracy, except for that of TBAs plus cholesterol. The concentration of TBAs plus cholesterol was overestimated in some cases, which could be due to lipid contamination. In addition, we report the first 2D L-COSY spectra of human gallbladder bile in vivo (obtained in 15 healthy volunteers). 2D L-COSY spectra will be helpful in differentiating various biliary chol-PLs in pathological conditions of the HPB system. PMID- 25132621 TI - Abusive supervision and links to nurse intentions to quit. AB - PURPOSE: To investigate forms of abusive supervision, namely personal attacks, task attacks, and isolation, and their links to outcomes for nurses, including job satisfaction, psychological strain, and intentions to quit. DESIGN: Cross sectional survey design. Data collected from July to November 2012. METHODS: Two hundred and fifty public sector nurses employed at five general acute Australian hospitals completed the survey (response rate of 33%). FINDINGS: Structural equation modeling on the forms of abusive supervision (personal, task, isolation) and nurse outcomes indicated goodness of fit statistics that confirmed a well fitting model, explaining 40% of the variance in intent to quit, 30% in job satisfaction, and 33% in strain. An indirect relationship from personal attacks to intentions to quit, via strain, was observed. Task attacks were related directly, and indirectly via job satisfaction, to increased intentions to quit. Surprisingly, isolation was positively related to job satisfaction. CONCLUSIONS: Abusive supervision impacted nurse outcomes. Specifically, personal abuse had personal and health impacts; work-focused abuse had work-oriented effects. Applying appraisal theory suggests that personal attacks are primarily assessed as stressful and unchangeable; task-oriented attacks are assessed as stressful, but changeable; and isolation is assessed as benign. The findings highlight the impact of abusive supervision, especially task attacks, on outcomes important to nurse retention. CLINICAL RELEVANCE: The findings can be used to devise programs to educate, train, and support supervisors and their subordinates to adhere to zero tolerance policies toward antisocial workplace behaviors and encourage reporting incidents. PMID- 25132623 TI - The role of a nanoparticle monolayer on the flow of polymer melts in nanochannels. AB - Understanding and controlling the flow properties of polymer melts at the nanoscale is of great relevance in fundamental research and in a variety of applications. In the present study we have analysed experimentally the flow behaviour of polymers in nanochannels of varying roughness, produced by gold nanoparticle absorption. The experimental results show that nanochannel roughness has a significant influence on surface energy and on the flow behaviour of polymer melts. These results provide fundamental information on the preparation of one-dimensional polymer nanochannels applicable in both micro- and nano injection technology. PMID- 25132622 TI - Patient preferences for treatments to delay bone metastases. AB - BACKGROUND: Most patients with advanced prostate cancer (PCa) develop bone metastases (BM) and present with bone complications like fracture. Bone-targeted agents that prevent metastasis-induced bone complications can cause adverse events. Understanding how patients view treatment options may optimize care. This study aimed to quantify how PCa patients value a hypothetical treatment that delays BM but can cause osteonecrosis of the jaw (ONJ). The study also assessed the value patients place on avoiding metastasis-induced bone complications versus increased survival. METHODS: PCa patients from the United Kingdom (n = 201) and Sweden (n = 200) on androgen-deprivation therapy or hormone therapy for >= 3 years completed a 10-question discrete-choice-experiment survey examining whether patients would accept a BM-delaying treatment. Two time-tradeoff questions assessed patients' willingness to tradeoff between survival and bone complications. Percentages of patients choosing treatment were summarized by levels of treatment efficacy and ONJ risk. Odds ratios from a logit model were used to evaluate how patient and medication characteristics affected treatment choice. Proportions of patients choosing each tradeoff scenario were calculated. RESULTS: A majority of patients accepted treatment at the lowest benefit level (5 month BM delay) and highest risk level (9% ONJ risk). PCa symptoms and prior treatment affected patient preferences. Nearly 80% of patients would tradeoff at least 3 months of survival to avoid bone complications. CONCLUSIONS: PCa patients in the U.K and Sweden may value a medication that delays BM, despite the risk of ONJ. Furthermore, patients were willing to tradeoff up to 5 months of survival for prevention of bone complications. PMID- 25132624 TI - Physiological and biochemical responses of three Veneridae clams exposed to salinity changes. AB - Given their global importance, coastal marine environments are a major focus of concern regarding the potential impacts of climate change, namely due to alterations in seawater salinity. It is known that environmental characteristics, such as salinity, affect immune and physiological parameters of bivalves. Nevertheless, scarce information is available concerning the biochemical alterations associated with salinity changes. For this reason, the present work aimed to evaluate the biochemical responses of three venerid clam species (Venerupis decussata, Venerupis corrugata, Venerupis philippinarum) submitted to salinity changes. The effects on the native (V. decussata and V. corrugata) and invasive (V. philippinarum) species collected from the same sampling site and submitted to the same salinity gradient (0 to 42g/L) were compared. The results obtained demonstrated that V. corrugata is the most sensitive species to salinity changes and V. decussata is the species that can tolerate a wider range of salinities. Furthermore, our work showed that clams under salinity associated stress can alter their biochemical mechanisms, such as increasing their antioxidant defenses, to cope with the higher oxidative stress resulting from hypo and hypersaline conditions. Among the physiological and biochemical parameters analyzed (glycogen and protein content; lipid peroxidation levels, antioxidant enzymes activity; total, reduced and oxidized glutathione) Catalase (CAT) and especially superoxide dismutase (SOD) showed to be useful biomarkers to assess salinity impacts in clams. PMID- 25132625 TI - Dynamic switching of the circularly polarized luminescence of disubstituted polyacetylene by selective transmission through a thermotropic chiral nematic liquid crystal. AB - The circularly polarized luminescence (CPL) of chiral disubstituted liquid crystalline polyacetylene (di-LCPA) can be dynamically switched and amplified from left- to right-handed CPL and vice versa through the selective transmission of CPL across a thermotropic chiral nematic liquid crystal (N*-LC) phase. By combining a chiral di-LCPA CPL-emitting film with an N*-LC cell and tuning the selective reflection band of the N*-LC phase to coincide with the CPL emission band, a CPL-switchable cell was constructed. The phase change induced by the thermotropic N*-LC cell by varying the temperature leads to a change in the selective transmission of CPL, which enables the dynamic switching and amplification of CPL. It is anticipated that CPL-switchable devices might find applications in switchable low-threshold lasers and optical memory devices. PMID- 25132628 TI - Repeal of the Sustainable Growth Rate: an overview for surgeons. AB - BACKGROUND: The Medicare sustainable growth rate (SGR) formula is used to control Medicare spending on physician services. Under the current SGR formula, physicians face an almost 24% cut to the Medicare fee schedule on April 1, 2015. The US House Way & Means and Energy & Commerce Committees and the Senate Finance Committee released jointly proposed legislation to permanently repeal the SGR, and transition Medicare physician payment to a value-based payment method. This review summarizes the key components of the proposed legislation, and discusses some of the political challenges ahead. DATA SOURCES: House Committees on Energy & Commerce and Ways & Means, and the Senate Committee on Finance staff write-ups. CONCLUSIONS: Physician Medicare reimbursement will move from a volume-based model to a value-based model over the next decade. Surgeons should remain engaged with the political process to ensure repeal of the SGR. PMID- 25132627 TI - Management of the pediatric spontaneous pneumothorax: is primary surgery the treatment of choice? AB - BACKGROUND: Surgery as the primary management strategy for pediatric primary spontaneous pneumothorax is controversial. This study aims to evaluate the outcomes and effectiveness of management approaches for pediatric spontaneous pneumothorax. METHODS: Outcomes of pediatric patients undergoing initial nonoperative treatment versus video-assisted thoracoscopic surgery with blebectomy and mechanical pleurodesis were compared via a retrospective review. RESULTS: We identified 96 patients with 108 pneumothoraces. Of 98 pneumothoraces with initial nonoperative management, 37% had surgery during their initial hospitalization for persistent air leak. Of those discharged home without video assisted thoracoscopic surgery, 40% recurred. Initial nonoperative management resulted in more total hospital days (median: 11 vs 5 days, P < .001). No significant predictors of recurrence were identified on multivariate analysis. Sixty-three percent of all patients ultimately required surgery. CONCLUSIONS: Fewer than 40% of primary spontaneous pneumothorax patients are definitively treated with nonoperative management. A prospective study is needed to determine whether primary surgery with blebectomy/mechanical pleurodesis is a more effective treatment strategy. PMID- 25132629 TI - Invited commentary on "Evaluation of a predictive model for pancreatic fistula based on amylase value in drains after pancreatic resection" by Partelli et al. PMID- 25132626 TI - Infant perceptual development for faces and spoken words: an integrated approach. AB - There are obvious differences between recognizing faces and recognizing spoken words or phonemes that might suggest development of each capability requires different skills. Recognizing faces and perceiving spoken language, however, are in key senses extremely similar endeavors. Both perceptual processes are based on richly variable, yet highly structured input from which the perceiver needs to extract categorically meaningful information. This similarity could be reflected in the perceptual narrowing that occurs within the first year of life in both domains. We take the position that the perceptual and neurocognitive processes by which face and speech recognition develop are based on a set of common principles. One common principle is the importance of systematic variability in the input as a source of information rather than noise. Experience of this variability leads to perceptual tuning to the critical properties that define individual faces or spoken words versus their membership in larger groupings of people and their language communities. We argue that parallels can be drawn directly between the principles responsible for the development of face and spoken language perception. PMID- 25132630 TI - Flow cytometry detection of minimal residual disease in multiple myeloma: Lessons learned at FDA-NCI roundtable symposium. PMID- 25132631 TI - Bridging of anions by hydrogen bonds in nest motifs and its significance for Schellman loops and other larger motifs within proteins. AB - The nest is a protein motif of three consecutive amino acid residues with dihedral angles 1,2-alphaR alphaL (RL nests) or 1,2-alphaL alphaR (LR nests). Many nests form a depression in which an anion or delta-negative acceptor atom is bound by hydrogen bonds from the main chain NH groups. We have determined the extent and nature of this bridging in a database of protein structures using a computer program written for the purpose. Acceptor anions are bound by a pair of bridging hydrogen bonds in 40% of RL nests and 20% of LR nests. Two thirds of the bridges are between the NH groups at Positions 1 and 3 of the motif (N1N3 bridging)-which confers a concavity to the nest; one third are of the N2N3 type which does not. In bridged LR nests N2N3-bridging predominates (14% N1N3: 75% N2N3), whereas in bridged RL nests the reverse is true (69% N1N3: 25% N2N3). Most bridged nests occur within larger motifs: 45% in (hexapeptide) Schellman loops with an additional 4 -> 0 hydrogen bond (N1N3), 11% in Schellman loops with an additional 5 -> 1 hydrogen bond (N2N3), 12% in a composite structure including a type 1beta-bulge loop and an asx- or ST- motif (N1N3)-remarkably homologous to the N1N3-bridged Schellman loop-and 3% in a composite structure including a type 2beta-bulge loop and an asx-motif (N2N3). A third hydrogen bond is a previously unrecognized feature of Schellman loops as those lacking bridged nests have an additional 4 -> 0 hydrogen bond. PMID- 25132632 TI - Environmental azole fungicide, prochloraz, can induce cross-resistance to medical triazoles in Candida glabrata. AB - Acquisition of azole resistance by clinically relevant yeasts in nature may result in a significant, yet undetermined, impact in human health. The main goal of this study was to assess the development of cross-resistance between agricultural and clinical azoles by Candida spp. An in vitro induction assay was performed, for a period of 90 days, with prochloraz (PCZ) - an agricultural antifungal. Afterward, the induced molecular resistance mechanisms were unveiled. MIC value of PCZ increased significantly in all Candida spp. isolates. However, only C. glabrata developed cross-resistance to fluconazole and posaconazole. The increased MIC values were stable. Candida glabrata azole resistance acquisition triggered by PCZ exposure involved the upregulation of the ATP binding cassette multidrug transporter genes and the transcription factor, PDR1. Single mutation previously implicated in azole resistance was found in PDR1 while ERG11 showed several synonymous single nucleotide polymorphisms. These results might explain why C. glabrata is so commonly less susceptible to clinical azoles, suggesting that its exposure to agricultural azole antifungals may be associated to the emergence of cross-resistance. Such studies forward potential explanations for the worldwide increasing clinical prevalence of C. glabrata and the associated worse prognosis of an infection by this species. PMID- 25132633 TI - Numerical investigations of the haemodynamic changes associated with stent malapposition in an idealised coronary artery. AB - The deployment of a coronary stent near complex lesions can sometimes lead to incomplete stent apposition (ISA), an undesirable side effect of coronary stent implantation. Three-dimensional computational fluid dynamics (CFD) calculations are performed on simplified stent models (with either square or circular cross section struts) inside an idealised coronary artery to analyse the effect of different levels of ISA to the change in haemodynamics inside the artery. The clinical significance of ISA is reported using haemodynamic metrics like wall shear stress (WSS) and wall shear stress gradient (WSSG). A coronary stent with square cross-sectional strut shows different levels of reverse flow for malapposition distance (MD) between 0mm and 0.12 mm. Chaotic blood flow is usually observed at late diastole and early systole for MD=0mm and 0.12 mm but are suppressed for MD=0.06 mm. The struts with circular cross section delay the flow chaotic process as compared to square cross-sectional struts at the same MD and also reduce the level of fluctuations found in the flow field. However, further increase in MD can lead to chaotic flow not only at late diastole and early systole, but it also leads to chaotic flow at the end of systole. In all cases, WSS increases above the threshold value (0.5 Pa) as MD increases due to the diminishing reverse flow near the artery wall. Increasing MD also results in an elevated WSSG as flow becomes more chaotic, except for square struts at MD=0.06 mm. PMID- 25132634 TI - Microsporidiosis in pediatric renal transplant patients in Cape Town, South Africa: two case reports. AB - Microsporidia are an emerging group of pathogens associated with life-threatening opportunistic infections in immunocompromised hosts, particularly human immunodeficiency virus (HIV)-infected individuals. There have, however, been recent reports of infection in adult solid organ transplant recipients. We report two cases in children, to our knowledge the first in the paediatric literature. Two 13-yr-old, HIV-seronegative females received deceased donor renal transplants from the same donor. Both patients suffered acute cell-mediated rejection and CMV infection reactivation, managed with intensified immunosuppression and ganciclovir. Pyrexia of unknown origin and intermittent diarrhea in both prompted extensive investigations. In both patients, numerous spores of a microsporidial species were demonstrated in renal tissue on biopsy and in the urine, using modified trichrome and quick-hot Gram-chromotrope staining. Electron microscopy and PCR confirmed Encephalitozoon cuniculi infections. Both patients were successfully treated with 400 mg twice daily of albendazole, with sustained clinical improvement. We recommend that microsporidiosis be considered in the differential diagnosis of pyrexia of unknown origin in severely immunocompromised pediatric solid organ transplant recipients, particularly when associated with diarrhea. PMID- 25132635 TI - Citrate versus heparin for apheresis catheter locks: an efficacy analysis. AB - INTRODUCTION: There is a paucity of medical literature regarding the efficacy of lock solutions in preventing catheter thrombosis. Traditionally, heparin has been used as the anticoagulant of choice for catheter locking, but it has many adverse effects associated with its use. Sodium citrate 4% is an attractive alternative to heparin. METHODS: Our plasmapheresis unit converted to locking all central venous catheters with sodium citrate 4% in place of heparin 100 units/mL in May 2010. We conducted a 2-year period retrospective observational cohort study comparing the outcomes of using heparin versus citrate locks. Outcomes examined were catheter patency, catheter exchanges, alteplase usage, and catheter infections. RESULTS: During the study period, 84 patients who underwent a total of 554 plasmapheresis treatments were identified. Flow problems among the citrate treatments were more frequent than those among the heparin group (6.5% vs. 3.2%, P = 0.11, n = 554) but this did not reach statistical significance. The frequency of more severe flow problems requiring catheter exchange or alteplase infusion was higher among the citrate group than the heparin group (3.2% vs. 1.3%, P = 0.11, n = 554). Subgroup analysis, stratified by diagnosis, demonstrated that there was a statistically significant difference in flow problems when comparing myasthenia gravis (MG) patients to non-MG patients. There was no difference in catheter infections between the groups. CONCLUSIONS: Based on the findings of our study, we conclude that citrate and heparin locks have similar efficacy in maintaining catheter patency in plasmapheresis patients. Further research is needed to examine the differences observed between MG patients versus all other patients. PMID- 25132636 TI - Mechanical properties and microstructure analysis of mineral trioxide aggregate mixed with hydrophilic synthetic polymer. AB - INTRODUCTION: In dentistry, mineral trioxide aggregate (MTA) has been widely used for root perforation, retrograde filling, pulp capping and regenerative endodontics. Despite its superior sealing ability and biocompatibility, MTA has critical drawbacks regarding handling property such as sandy property, lacking cohesive properties and wash-out tendency. So, it is necessary to improve the fluidity of MTA in order to improve its handling properties. In this study, we applied modified liquid to improve handling properties of MTA. METHODS: Polyvinyl alcohol (PVA; 3 and 5 wt %) aqueous solutions were prepared and the samples were divided into three groups: DW group (MTA mixed with distilled water), P3 group (MTA mixed with 3% PVA), and P5 group (MTA mixed with 5% PVA). Handling property, initial setting time, and compressive strength were evaluated. The microstructures were observed by Field emission scanning electron microscope (FE SEM) and X-ray diffractometer (XRD) phase analyses were performed. RESULTS: PVA modified group showed similar behavior of IRM compared to DW group. The initial setting time of P3 or P5 group was significantly longer than that of DW group (p < 0.05). The compressive strength of DW group was higher than that of P3 or P5 groups (p < 0.05). Experimental groups (P3 and P5) showed no microstructural differences compared with DW group when the fractured surfaces were observed by FE-SEM with XRD patterns after 3 and 14 days. CONCLUSIONS: Polyvinyl alcohol, a modified liquid for MTA, improved the handling properties of the material without violating its microstructure. PMID- 25132637 TI - Photoinitiated [corrected] charge separation in a hybrid titanium dioxide metalloporphyrin peptide material. AB - In natural systems, electron flow is mediated by proteins that spatially organize donor and acceptor molecules with great precision. Achieving this guided, directional flow of information is a desirable feature in photovoltaic media. Here, we design self-assembled peptide materials that organize multiple electronic components capable of performing photoinduced charge separation. Two peptides, c16-AHL3K3-CO2H and c16-AHL3K9-CO2H, self-assemble into fibres and provide a scaffold capable of binding a metalloporphyrin via histidine axial ligation and mineralize titanium dioxide (TiO2) on the lysine-rich surface of the resulting fibrous structures. Electron paramagnetic resonance studies of this self-assembled material under continuous light excitation demonstrate charge separation induced by excitation of the metalloporphyrin and mediated by the peptide assembly structure. This approach to dye-sensitized semiconducting materials offers a means to spatially control the dye molecule with respect to the semiconducting material through careful, strategic peptide design. PMID- 25132638 TI - Bionanotechnology: arrays in the future prospects of the field. PMID- 25132639 TI - Molecular fingerprint similarity search in virtual screening. AB - Molecular fingerprints have been used for a long time now in drug discovery and virtual screening. Their ease of use (requiring little to no configuration) and the speed at which substructure and similarity searches can be performed with them - paired with a virtual screening performance similar to other more complex methods - is the reason for their popularity. However, there are many types of fingerprints, each representing a different aspect of the molecule, which can greatly affect search performance. This review focuses on commonly used fingerprint algorithms, their usage in virtual screening, and the software packages and online tools that provide these algorithms. PMID- 25132640 TI - SFAPS: an R package for structure/function analysis of protein sequences based on informational spectrum method. AB - The R package SFAPS has been developed for structure/function analysis of protein sequences based on information spectrum method. The informational spectrum method employs the electron-ion interaction potential parameter as the numerical representation for the protein sequence, and obtains the characteristic frequency of a particular protein interaction after computing the Discrete Fourier Transform for protein sequences. The informational spectrum method is often used to analyze protein sequences, so we developed this software tool, which is implemented as an add-on package to the freely available and widely used statistical language R. Our package is distributed as open source code for Linux, Unix and Microsoft Windows. It is released under the GNU General Public License. The R package along with its source code and additional material are freely available at http://mlsbl.tongji.edu.cn/DBdownload.asp. PMID- 25132641 TI - Predictors and incidence of post-partum depression: a longitudinal cohort study. AB - AIM: This study was designed to identify the incidence and the related factors contributing to post-partum depression (PPD) in women in Iran for the first time. MATERIAL AND METHODS: A total of 2279 eligible pregnant women from 32-42 weeks of pregnancy to 12 weeks post-partum (2009) who attended primary health centers in Mazandaran province were screened for depression using the Iranian version of the Edinburgh Postnatal Depression Scale. Pregnant women free from depression were assessed using validated questionnaires, including the Premenstrual Syndrome Questionnaire, Social Support Appraisal Scale, Network Orientation Scale, General Health Questionnaire, Marital Inventory, Life Events Rating Scale and Parental Expectation Survey. Logistic regression analysis was used to determine the risk factors of PPD. RESULTS: Of 1801 women who screened negative for depression at 32 42 weeks' gestation, cumulative incidence proportions were 6.7%, 4.3% and 4.5% during 0-2, >2-8 and >8-12 weeks post-partum, respectively. The factors predictive of PPD were: history of depression during the first two trimesters of pregnancy (odds ratio [OR] = 2.55, 95% confidence interval [CI] = 1.59-4.1); psychiatric disorder during pregnancy (OR = 1.08, 95%CI = 1.06-1.11); gestational diabetes (OR = 2.93, 95%CI = 1.46-5.88); recurrent urinary infection (OR = 2.25, 95%CI = 1.44-3.52); unwanted pregnancy (OR = 2.5, 95%CI = 1.69-3.7) and low household income (OR = 3.57, 95%CI = 1.49-8.5). The risk was decreased with increasing age (OR = 0.88, 95%CI = 0.84-0.92) and those with high self-efficacy for mothering (OR = 0.7, 95%CI = 0.62-0.78). CONCLUSION: A high rate of new cases of PPD was identified in Iranian women. A combination of psychological, sociological, obstetric and sociodemographic factors can render mothers vulnerable to post-partum depression. PMID- 25132643 TI - Mechanism of 2',3'-dimethoxyflavanone-induced apoptosis in breast cancer stem cells: role of ubiquitination of caspase-8 and LC3. AB - Accumulating evidence has displayed that targeting cancer stem cells (CSCs) is a very promising way for anti-cancer therapies. 2',3'-Dimethoxyflavanone (2',3' DMF) showed the most potent toxicity of a group of 42 flavonoids tested in MCF-7 SC breast cancer stem cells. 2',3'-DMF triggered intrinsic and extrinsic apoptosis by stimulating the cleavage of PARP and the activation of caspase-9, 8, and -3. Interestingly, 2',3'-DMF induces a dramatic increase in the conversion of LC3, a well-known marker for autophagy. However, acidic vesicular organelles (AVOs), one of the autophagic flux markers were not detected. Co-treatment with chloroquine, the lysosomal inhibitor that blocks autophagic degradation did not show any change in the degree of LC3 conversion, implying that LC3 could play a role in the non-autophagic cell death of MCF-7-SC. We found that 2',3'-DMF induces the ubiquitination of caspase-8, this resulted in an interaction between caspase-8 and LC3, which led to the aggregation and activation of caspase-8. Co treating cells with 2',3'-DMF and 3-methyladenine, an inhibitor of LC3 lipidation, reduced the activation of caspase-8. These findings provide novel insights into the anti-cancer effects of 2',3'-DMF in breast cancer stem cells by revealing that it induced apoptosis in accompany with the activation of caspase-8 mediated by LC3 conversion. PMID- 25132642 TI - Targeting melanocyte and melanoma stem cells by 8-hydroxy-2 dipropylaminotetralin. AB - Monobenzyl ether of hydroquinone (MBEH) is cytotoxic towards melanocytes. Its treatment efficacy is limited by an inability to eradicate stem cells. By contrast, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-DPAT) affects melanocyte stem cell survival. MBEH and 8-DPAT were added to melanocytes and melanoma cells to compare cytotoxicity. Stem cell content among viable cells was determined by fluorocytometry using markers CD34, Pax3, and CD271. Immunostaining was used to identify stem cells in skin explants treated with MBEH or 8-DPAT ex vivo. Mice were exposed to MBEH or 8-DPAT and scanned for depigmentation before harvesting skin. MBEH exposure prompted a relative increase in stem cells among cultured melanocytes and melanoma cells, as treatment preferentially eliminated differentiated cells and spared the stem cells. Viability of this remaining, enriched stem cell population was however rapidly reduced by exposure to 8-DPAT within melanocyte and melanoma cell cultures. In human skin explants, the abundance of melanocyte stem cells was also visibly reduced after 8-DPAT treatment, in contrast to tissue exposed to MBEH. Meanwhile, significant depigmentation of the mouse pelage and loss of differentiated melanocytes was observed in vivo in response to topical application of MBEH, but not 8-DPAT. Prolonged application of the latter agent instead appeared to effectively reduce the abundance of melanocyte stem cells in the dermis. This furthers the idea that MBEH and 8-DPAT target complementary cell populations. Results indicate that combination treatment may demonstrate superior therapeutic activity by eliminating both differentiated and tumor initiating populations. PMID- 25132644 TI - Hyper-coupling between working memory task-evoked activations and amplitude of spontaneous fluctuations in first-episode schizophrenia. AB - Working memory (WM) deficit is an important component of impaired cognition in schizophrenia. However, between-studies inconsistencies as to the specific functional substrate imply that inter-individual variability (IIV) in the WM performance is associated with IIV in brain activity in schizophrenia. To examine the neural substrate of this WM IIV, we studied whether the neural mechanisms that underlie individual differences in WM capacity are the same in schizophrenia patients and healthy people. We correlated the IIV of the task-evoked brain activity and task performance during an n-back WM task with the IIV of the moment to-moment variability in intrinsic resting-state activity, as measured by the amplitude of low-frequency fluctuations (ALFFs) and further compared this relationship between 17 patients with first-episode schizophrenia (FES) and 18 healthy controls. Between-group comparisons of the correlation patterns indicated aberrant ALFF-WM activation correlations and ALFF-WM performance correlations in the FES patients, but no significant changes were detected in any single measurement of these three characteristics. Specifically, we found increased positive ALFF-WM activation correlations in the bilateral lateral prefrontal cortices, posterior parietal cortices and fusiform gyri in the FES patients. We also observed significant increases in positive ALFF-WM performance correlations in the bilateral ventromedial prefrontal cortices in the FES patients. This hyper coupling between the ALFF and fMRI measures during a WM task may indicate that it was difficult for the patients to detach themselves from one state to transition to another and suggests that the inefficient cortical function in schizophrenia stems from the intrinsic functional architecture of the brain. PMID- 25132645 TI - Oncoplastic mammaplasty with geometric compensation--a technique for breast conservation. AB - OBJECTIVE: To describe a technique of oncoplastic mammaplasty, referred to as geometric compensation, which is suitable for tumors close to the skin in areas not included in the classic preoperative drawings for mammaplasty. MATERIALS AND METHODS: Seventeen patients with malignant tumors were included. Preoperative markings followed the "Wise-pattern" technique. The resection of affected skin was geometrically compensated with another area of preserved skin. RESULTS: The mean age of the patients was 52.88 +/- 12.14 years. Mean pathological tumor size was 43.82 +/- 31.39 mm. There were 7 (41.18%) locally advanced tumors. Six patients (35.29%) were submitted to neoadjuvant and the remainder to adjuvant chemotherapy. Radiotherapy was indicated in all cases. Fifteen patients (88.24%) received hormone therapy. Ptosis was corrected in all cases. The aesthetic result was rated excellent in seven cases (41.18%), good in 7 (41.18%), and fair in three cases (17.65%). Surgical margins were free. A seroma developed in one case (5.88%), small fat necrosis in three (17.65%), and enlarged scar in one (5.88%). There were no recurrences within 28.24 +/- 18.02 months. CONCLUSIONS: The technique allowed breast conservation in situations requiring large resection of affected skin, with free surgical margins, correction of ptosis, satisfactory symmetry, and few complications. PMID- 25132646 TI - Upper bounds on FST in terms of the frequency of the most frequent allele and total homozygosity: the case of a specified number of alleles. AB - FST is one of the most frequently-used indices of genetic differentiation among groups. Though FST takes values between 0 and 1, authors going back to Wright have noted that under many circumstances, FST is constrained to be less than 1. Recently, we showed that at a genetic locus with an unspecified number of alleles, FST for two subpopulations is strictly bounded from above by functions of both the frequency of the most frequent allele (M) and the homozygosity of the total population (HT). In the two-subpopulation case, FST can equal one only when the frequency of the most frequent allele and the total homozygosity are 1/2. Here, we extend this work by deriving strict bounds on FST for two subpopulations when the number of alleles at the locus is specified to be I. We show that restricting to I alleles produces the same upper bound on FST over much of the allowable domain for M and HT, and we derive more restrictive bounds in the windows M?[1/I,1/(I-1)) and HT?[1/I,I/(I(2)-1)). These results extend our understanding of the behavior of FST in relation to other population-genetic statistics. PMID- 25132648 TI - Oxygen sensing and metabolic homeostasis. AB - Oxygen-sensing mechanisms have evolved to maintain cell and tissue homeostasis since the ability to sense and respond to changes in oxygen is essential for survival. The primary site of oxygen sensing occurs at the level of the carotid body which in response to hypoxia signals increased ventilation without the need for new protein synthesis. Chronic hypoxia activates cellular sensing mechanisms which lead to protein synthesis designed to alter cellular metabolism so cells can adapt to the low oxygen environment without suffering toxicity. The master regulator of the cellular response is hypoxia-inducible factor (HIF). Activation of this system under condition of hypobaric hypoxia leads to weight loss accompanied by increased basal metabolic rate and suppression of appetite. These effects are dose dependent, gender and genetic specific, and results in adverse effects if the exposure is extreme. Hypoxic adipose tissue may represent a unified cellular mechanism for variety of metabolic disorders, and insulin resistance in patients with metabolic syndrome. PMID- 25132647 TI - The expression of aminoacyl-tRNA-synthetase-interacting multifunctional protein-1 (Aimp1) is regulated by estrogen in the mouse uterus. AB - Aimp1 is known as a multifunctional cytokine in various cellular events. Recent study showed Aimp1 is localized in glandular epithelial, endothelial, and stromal cells in functionalis and basalis layers of the endometrium. However, the regulatory mechanism of Aimp1 in the uterus remains unknown. In the present study, we found that Aimp1 is expressed in the mouse uterus. Aimp1 transcripts were decreased at diestrus stage. However, the level of Aimp1 protein was significantly increased in the luminal epithelium in the uterine endometrium at estrus stage during the estrous cycle. We found that treatment of estrogen increased the expression of Aimp1 in the uterus in ovarectomized mice. We identified one estrogen receptor binding element (ERE) on mouse Aimp1 promoter. The activity of Aimp1 promoter was increased with estrogen treatment. Our findings indicate that Aimp1 might act as an important regulator to remodel the uterine endometrium and its expression might be regulated by estrogen during the estrous cycle. This will give us better understanding of the dynamic change of uterine remodeling during the estrous cycle. PMID- 25132649 TI - The three-factor structure of the Levenson self-report psychopathy scale: fool's gold or true gold? A study in a sample of Italian adult non-clinical participants. AB - The major aim of this study was to evaluate the factor structure of the Italian translation of the Levenson Self-Report Psychopathy Scale (LSRP) in a sample of 740 community dwelling adult participants. Hull method, minimum average partial analysis and quasi-inferential parallel analysis techniques were used to identify a three-factor solution that appeared broadly consistent with previous work. The three factors exhibited reliability coefficients >0.70, and the three-factor structure was adequately reproduced across gender, educational level and civil status strata (median congruence coefficients = 0.94, 0.93 and 0.95 respectively) and remained largely unchanged when the effect of participants' age was controlled for (median factor score correlation = 0.99). Although Factor 3 in our study was demarcated mainly by reverse-keyed items, the LSRP factors yielded meaningful relations with retrospective measures of antisocial behaviour in adolescence and HEXACO personality traits and were conceptually consistent with the triarchic model of psychopathy of Patrick, Fowles and Krueger (2009). PMID- 25132650 TI - Prophylactic stretching is unlikely to prevent nocturnal leg cramps. PMID- 25132651 TI - Depression and psychosocial correlates of liver transplant candidates: a systematic review. AB - INTRODUCTION: Liver transplant candidates are vulnerable to develop depression. This paper aims to ascertain the prevalence of depression in liver transplant candidates and its psychosocial factors in a systematic review. METHODS: An extensive review via electronic databases (PubMed, EMBASE, CINAHL) and hand search were carried out to retrieve published articles up to December 15, 2013, using (Incidence OR Prevalence) AND Depress* AND liver transplant as the keywords. Information on the study design, patient characteristics, prevalence of depression, and its associated risk factors were extracted from included studies. RESULTS: There were 22 studies included in this review with a total of 3055 patients. The prevalence of depression in the liver transplant candidates ranges between 2% and 80%. Studies that used diagnostic tools found a narrower range of prevalence (4.5-43%) as compared to the self-administered questionnaires (2-80%). Studies that used Beck Depression Inventory reported a higher prevalence than those studies which used Hospital Anxiety and Depression Scale (median = 28%, range = 2-80% versus median 17%, range 6.1-25.8%). A number of socio-demographic factors, illness-related and psychosocial factors were found to be associated with depression. CONCLUSION: Prevalence of depression in liver transplant candidates is high, and early detection will improve survival and quality of life. PMID- 25132652 TI - Distinct driver mutation profiles of childhood and adolescent essential thrombocythemia. PMID- 25132654 TI - Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia. AB - Platelet survival depends upon mediators of apoptosis e.g., Bcl-xL, Bax, and Bak, which are regulated by thrombopoietin (TPO)-mediated AKT signaling. Thrombopoietin receptor (TPO-R) signaling might decrease platelet and/or megakaryocyte apoptosis and increase the platelet count. This study therefore explored anti-apoptotic effects of TPO-R-agonists in vivo on platelets of patients with immune thrombocytopenia. Patients received eltrombopag or romiplostim for two weeks. Total, immature, and large platelet counts were assessed as were Bcl-xL inhibitor assay; Bcl-xL Western blot; and flow cytometric (FACS) analysis of the AKT-signaling pathway. Eight/ten patients had platelet responses to eltrombopag and all three to romiplostim. Platelet sensitivity to apoptosis by Bcl-xL inhibition was greater in pretreatment patients than controls. This sensitivity normalized after one week of therapy, but surprisingly returned to pretreatment levels at week two. FACS analysis revealed increased AKT pathway signaling after one week, followed by a decrease at week two. Platelet counts correlated with the Bcl-xL /Bak ratio. Platelet survival may be enhanced by TPO-R-agonists as a transient decrease in platelet sensitivity to apoptosis was accompanied by transient activation of AKT. However, this mechanism has only a short-lived effect. Megakaryocytes and platelets already present at the start of TPO-R-agonist treatment appear to respond differently than those generated de novo. PMID- 25132653 TI - Childhood maltreatment and combat posttraumatic stress differentially predict fear-related fronto-subcortical connectivity. AB - BACKGROUND: Adult posttraumatic stress disorder (PTSD) has been characterized by altered fear-network connectivity. Childhood trauma is a major risk factor for adult PTSD, yet its contribution to fear-network connectivity in PTSD remains unexplored. We examined, within a single model, the contribution of childhood maltreatment, combat exposure, and combat-related posttraumatic stress symptoms (PTSS) to resting-state connectivity (rs-FC) of the amygdala and hippocampus in military veterans. METHODS: Medication-free male veterans (n = 27, average 26.6 years) with a range of PTSS completed resting-state fMRI. Measures including the Clinician-Administered PTSD Scale (CAPS), Childhood Trauma Questionnaire (CTQ), and Combat Exposure Scale (CES) were used to predict rs-FC using multilinear regression. Fear-network seeds included the amygdala and hippocampus. RESULTS: Amygdala: CTQ predicted lower connectivity to ventromedial prefrontal cortex (vmPFC), but greater anticorrelation with dorsal/lateral PFC. CAPS positively predicted connectivity to insula, and loss of anticorrelation with dorsomedial/dorsolateral (dm/dl)PFC. Hippocampus: CTQ predicted lower connectivity to vmPFC, but greater anticorrelation with dm/dlPFC. CES predicted greater anticorrelation, whereas CAPS predicted less anticorrelation with dmPFC. CONCLUSIONS: Childhood trauma, combat exposure, and PTSS differentially predict fear-network rs-FC. Childhood maltreatment may weaken ventral prefrontal subcortical circuitry important in automatic fear regulation, but, in a compensatory manner, may also strengthen dorsal prefrontal-subcortical pathways involved in more effortful emotion regulation. PTSD symptoms, in turn, appear to emerge with the loss of connectivity in the latter pathway. These findings suggest potential mechanisms by which developmental trauma exposure leads to adult PTSD, and which brain mechanisms are associated with the emergence of PTSD symptoms. PMID- 25132655 TI - The heat-compression technique for the conversion of platelet-rich fibrin preparation to a barrier membrane with a reduced rate of biodegradation. AB - Platelet-rich fibrin (PRF) was developed as an advanced form of platelet-rich plasma to eliminate xenofactors, such as bovine thrombin, and it is mainly used as a source of growth factor for tissue regeneration. Furthermore, although a minor application, PRF in a compressed membrane-like form has also been used as a substitute for commercially available barrier membranes in guided-tissue regeneration (GTR) treatment. However, the PRF membrane is resorbed within 2 weeks or less at implantation sites; therefore, it can barely maintain sufficient space for bone regeneration. In this study, we developed and optimized a heat compression technique and tested the feasibility of the resulting PRF membrane. Freshly prepared human PRF was first compressed with dry gauze and subsequently with a hot iron. Biodegradability was microscopically examined in vitro by treatment with plasmin at 37 degrees C or in vivo by subcutaneous implantation in nude mice. Compared with the control gauze-compressed PRF, the heat-compressed PRF appeared plasmin-resistant and remained stable for longer than 10 days in vitro. Additionally, in animal implantation studies, the heat-compressed PRF was observed at least for 3 weeks postimplantation in vivo whereas the control PRF was completely resorbed within 2 weeks. Therefore, these findings suggest that the heat-compression technique reduces the rate of biodegradation of the PRF membrane without sacrificing its biocompatibility and that the heat-compressed PRF membrane easily could be prepared at chair-side and applied as a barrier membrane in the GTR treatment. PMID- 25132656 TI - Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening. AB - BACKGROUND: Dual-stain cytology for p16 and Ki-67 has been proposed as a biomarker in cervical cancer screening. The authors evaluated the reproducibility and accuracy of dual-stain cytology among 10 newly trained evaluators. METHODS: In total, 480 p16/Ki-67-stained slides from human papillomavirus-positive women were evaluated in masked fashion by 10 evaluators. None of the evaluators had previous experience with p16 or p16/Ki-67 cytology. All participants underwent p16/Ki-67 training and subsequent proficiency testing. Reproducibility of dual stain cytology was measured using the percentage agreement, individual and aggregate kappa values, as well as McNemar statistics. Clinical performance for the detection of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) was evaluated for each individual evaluator and for all evaluators combined compared with the reference evaluation by a cytotechnologist who had extensive experience with dual-stain cytology. RESULTS: The percentage agreement of individual evaluators with the reference evaluation ranged from 83% to 91%, and the kappa values ranged from 0.65 to 0.81. The combined kappa value was 0.71 for all evaluators and 0.73 for cytotechnologists. The average sensitivity and specificity for the detection of CIN2+ among novice evaluators was 82% and 64%, respectively; whereas the reference evaluation had 84% sensitivity and 63% specificity, respectively. Agreement on dual-stain positivity increased with greater numbers of p16/Ki-67-positive cells on the slides. CONCLUSIONS: Good to excellent reproducibility of p16/Ki-67 dual-stain cytology was observed with almost identical clinical performance of novice evaluators compared with reference evaluations. The current findings suggest that p16/Ki-67 dual-stain evaluation can be implemented in routine cytology practice with limited training. PMID- 25132658 TI - Cell culture media supplementation of uncommonly used sugars sucrose and tagatose for the targeted shifting of protein glycosylation profiles of recombinant protein therapeutics. AB - Protein glycosylation is an important post-translational modification toward the structure and function of recombinant therapeutics. The addition of oligosaccharides to recombinant proteins has been shown to greatly influence the overall physiochemical attributes of many proteins. It is for this reason that protein glycosylation is monitored by the developer of a recombinant protein therapeutic, and why protein glycosylation is typically considered a critical quality attribute. In this work, we highlight a systematic study toward the supplementation of sucrose and tagatose into cell culture media for the targeted modulation of protein glycosylation profiles on recombinant proteins. Both sugars were found to affect oligosaccharide maturation resulting in an increase in the percentage of high mannose N-glycan species, as well as a concomitant reduction in fucosylation. The latter effect was demonstrated to increase antibody dependent cell-mediated cytotoxicity for a recombinant antibody. These aforementioned results were found to be reproducible at different scales, and across different Chinese hamster ovary cell lines. Through the selective supplementation of these described sugars, the targeted modulation of protein glycosylation profiles is demonstrated, as well as yet another tool in the cell culture toolbox for ensuring product comparability. PMID- 25132659 TI - Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics. AB - BACKGROUND: Mutations in the RAS gene in the thyroid gland result in the activation of signaling pathways and are associated with a follicular growth pattern and the probability of a carcinoma outcome ranging from 74% to 87%. In the current study, the authors investigated the cytopathologic and histopathologic features of common RAS mutation subtypes. METHODS: Malignant, indeterminate, and selected benign thyroid cytology cases were tested prospectively for the presence of NRAS61, HRAS61, and KRAS12/13 mutations. For each case, the Bethesda System for thyroid cytopathology diagnosis, additional cytologic descriptors, and surgical pathology outcomes were documented. The Fisher exact test and Wilcoxon 2-sample test were used for statistical comparison between the groups. RESULTS: A total of 204 thyroid fine-needle aspiration cases with RAS mutations (93.6% of which were associated with indeterminate cytopathology diagnoses) and corresponding surgical pathology resection specimens were identified. The KRAS12/13 mutation was associated with a significantly lower carcinoma outcome (41.7%) when compared with HRAS61 (95.5%) and NRAS61 (86.8%) mutations (P<.0001). Furthermore, oncocytic change was observed in a significantly higher percentage of cytology and resection specimens with KRAS12/13 mutations (66.7% and 75.0%, respectively) in comparison with those with HRAS61 (4.5% and 4.5%, respectively) and NRAS61 (15.4% and 14.7%, respectively) mutations (P<.0001). RAS mutations also were identified in cases of poorly differentiated carcinoma (NRAS61), anaplastic carcinoma (HRAS61), and medullary thyroid carcinoma (HRAS61 and KRAS12/13). CONCLUSIONS: Subclassification of RAS mutations in conjunction with cytopathologic evaluation improves presurgical risk stratification, provides better insight into lesional characteristics, and may influence patient management. In particular, KRAS12/13-mutated thyroid nodules were found to be different from HRAS61-mutated and NRAS61-mutated nodules with regard to cytopathologic and surgical outcome characteristics. PMID- 25132657 TI - Decreased in vivo virulence and altered gene expression by a Brucella melitensis light-sensing histidine kinase mutant. AB - Brucella species utilize diverse virulence factors. Previously, Brucella abortus light-sensing histidine kinase was identified as important for cellular infection. Here, we demonstrate that a Brucella melitensis LOV-HK (BM-LOV-HK) mutant strain has strikingly different gene expression than wild type. General stress response genes including the alternative sigma factor rpoE1 and its anti anti-sigma factor phyR were downregulated, while flagellar, quorum sensing (QS), and type IV secretion system genes were upregulated in the DeltaBM-LOV-HK strain vs. wild type. Contextually, expression results agree with other studies of transcriptional regulators involving DeltarpoE1, DeltaphyR, DeltavjbR, and DeltablxR (DeltababR) Brucella strains. Additionally, deletion of BM-LOV-HK decreases virulence in mice. During C57BL/6 mouse infection, the DeltaBM-LOV-HK strain had 2 logs less CFUs in the spleen 3 days postinfection, but similar levels 6 days post infection compared to wild type. Infection of IRF-1(-/-) mice more specifically define DeltaBM-LOV-HK strain attenuation with fewer bacteria in spleens and significantly increased survival of mutant vs. wild-type infected IRF 1(-/-) mice. Upregulation of flagella, QS, and VirB genes, along with downregulation of rpoE1 and related sigma factor, rpoH2 (BMEI0280) suggest that BM-LOV-HK modulates both QS and general stress response regulatory components to control Brucella gene expression on a global level. PMID- 25132660 TI - Interactions between patients, providers, and health systems and technical quality of care. AB - OBJECTIVE: Prior studies have established disparities by race/ethnicity and socioeconomic status (SES) in the kind, quantity, and technical quality of systemic lupus erythematosus (SLE) care and outcomes. In this study we evaluate whether disparities exist in assessments of interactions with health care providers and health plans and whether such interactions affect the technical quality of SLE care. METHODS: Data derive from the Lupus Outcomes Study (LOS). Principal data collection is an annual structured phone interview including items from the Consumer Assessment of Health Plans and Interpersonal Processes of Care Scale measuring dimensions of health care interactions. We use general estimating equations to assess whether disparities exist by race/ethnicity and SES in being in the lowest quartile of ratings of such interactions and whether ratings in the lowest quartile of interactions are associated with technical quality of care after adjustment for sociodemographic and disease characteristics. RESULTS: In the 2012 LOS interview, there were 793 respondents, of whom 640 had >=1 visit to their principal SLE provider. Nonwhite race/ethnicity and education were not associated with low ratings on any dimension of provider or system interaction; poverty was associated only with low ratings of health plan interactions. After adjustment for demographics, SLE status, and health care variables, ratings in the lowest quartile on all dimensions were associated with significantly lower technical quality of care. CONCLUSION: Ratings in the lowest quartile on all dimensions of interactions with providers and the health care system were associated with lower technical quality of care, potentially resulting in poorer SLE outcomes. PMID- 25132661 TI - Integration of medical imaging including ultrasound into a new clinical anatomy curriculum. AB - In 2008 a new clinical anatomy curriculum with integrated medical imaging component was introduced into the University of Sydney Medical Program. Medical imaging used for teaching the new curriculum included normal radiography, MRI, CT scans, and ultrasound imaging. These techniques were incorporated into teaching over the first two years of the program as a part of anatomy practical sessions, in addition to dedicated lectures and tutorials given by imaging specialists. Surveys were conducted between 2009 and 2012 to evaluate the student acceptance of the integration. Students were asked to rate individual activities as well as provide open-ended comments. The number of students who responded to the surveys varied from 40% to 98%. Over 90% of the respondents were satisfied with the overall quality of teaching in the anatomy units. In summary, 48% to 63% of the responding students thought that the specialist imaging lectures helped them learn effectively; 72% to 77% of students thought that the cross-sectional practical sessions helped them to better understand the imaging modalities of CT, MRI, and ultrasound; 76% to 80% of students considered hands-on ultrasound session to be useful in understanding the application of ultrasound in abdominal imaging. The results also revealed key similarities and differences in student perceptions of the new integrated curriculum for students with both a high and low prior exposure to anatomy. Further evaluation will aid in refining the integrated medical imaging program and providing its future direction. PMID- 25132663 TI - Incidence of giant cell arteritis and characteristics of patients: data-driven analysis of comorbidities. AB - OBJECTIVE: To establish the incidence of giant cell arteritis (GCA), cumulative use of prednisolone, and comorbidities most associated with GCA. METHODS: The data source was the UK Clinical Practice Research Datalink. Selection criteria included >=1 record of a diagnostic term for GCA between January 1, 2000 and December 31, 2011, age >=50 years, and >=1 prescription of oral or systemic corticosteroid. Controls were selected randomly (2:1), with year of birth, practice, and followup duration (<2 or >=2 years) as matching variables. Analysis was data driven; all comorbidities were identified in a 2-year window, with relative risk (RR) calculated and rank ordered. RESULTS: A total of 4,671 patients fulfilled the definition of GCA (incidence, 1.0 per 10,000 person years), with highest incidence (7.4 per 10,000 person-years) in women ages 70-79 years. Of the 4,671 patients, 4,655 (99.7%) were prescribed prednisolone. In the group with >=2 years' followup (n = 3,074), the mean number of prednisolone prescriptions was 32.1, and the mean cumulative dose was 8,640 mg; 1,034 patients (33.4%) received a cumulative dose of >=10,000 mg. Comorbidities strongly associated with GCA were polymyalgia rheumatica (RR 14.9, 95% confidence interval [95% CI] 11.9-18.7), visual disturbances (RR 4.6, 95% CI 2.7-7.8), facial pain (RR 3.3, 95% CI 2.1-5.3), osteoporosis (RR 2.9, 95% 2.3-3.7), hypokalemia (RR 2.5, 95% CI 1.6-3.9), and various infections such as oral/esophageal thrush (RR 3.7, 95% CI 2.2-6.0) and herpes zoster (RR 2.6, 95% CI 1.6-4.1). CONCLUSION: GCA is relatively uncommon; its incidence peaks at age 70-79 years in women. Overall, GCA patients in the UK are treated with high cumulative prednisolone doses. Many conditions are associated with GCA, including several related to corticosteroid use. PMID- 25132664 TI - Integration of gross anatomy in an organ system-based medical curriculum: strategies and challenges. AB - The University of Alabama School of Medicine (UASOM) instituted a fully integrated, organ system-based preclinical curriculum in 2007. Gross anatomy and embryology were integrated with other basic science disciplines throughout the first two years of undergraduate medical education. Here we describe the methods of instruction and integration of gross anatomy and embryology in this curriculum as well as challenges faced along the way. Gross anatomy and embryology are taught through a combination of didactic lectures, team-based learning activities, and cadaveric dissection laboratories. Vertical integration occurs through third- and fourth-year anatomy and embryology elective courses. Radiology is integrated with anatomy instruction through self-study modules and hands-on ultrasound sessions. Our model of anatomy instruction is time efficient, clinically relevant, and effective as demonstrated by student performance on the United States Medical Licensing Examination((r)) (USMLE((r)) ) Step 1 examination. We recommend that medical schools considering full integration of gross anatomy and embryology (1) carefully consider the sequencing of organ system modules, (2) be willing to sacrifice anatomical detail for clinical application, (3) provide additional electives to third- and fourth-year students, and (4) integrate radiology with anatomical education. PMID- 25132662 TI - Using surgical appropriateness criteria to examine outcomes of total knee arthroplasty in a United States sample. AB - OBJECTIVE: We determined outcomes for patients classified as appropriate, inconclusive, or inappropriate for total knee arthroplasty (TKA) using a modified version of a validated appropriateness algorithm. Outcome measurement was conceptualized as short-term postoperative change attributable primarily to surgery and rehabilitation (2 months) and as longer-term postoperative change and recovery (1 and 2 years). METHODS: Preoperative and yearly postoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function, Knee Injury and Osteoarthritis Outcome Score (KOOS) symptoms and KOOS pain scores were examined for persons undergoing primary TKA in the Osteoarthritis Initiative. Multigroup, 2-piece latent growth curve modeling was used to determine differences in outcome variable changes for each group from presurgery to 2 months postsurgery, as well as over a 2-year postoperative period. RESULTS: Data from 167 persons with primary TKA were examined. Prevalence rates of appropriate, inconclusive, and inappropriate judgments were 47.9%, 20.8%, and 31.3%, respectively. The inappropriate group showed no change at 2 months following surgery, while appropriate and inconclusive groups had substantial improvement in all outcomes. One-year and 2-year postoperative recovery outcomes were not significantly different among the 3 groups. CONCLUSION: The inappropriate group was unchanged 2 months after surgery and on average improved by 2.3 WOMAC function points from presurgery to 1 year following surgery based on our models. Appropriate and inconclusive groups improved by an average of 19.8 WOMAC function points at 1-year postsurgery. These data provide a compelling case for consensus building efforts to define eligibility criteria for TKA with the goals of reducing variation in patient selection and optimizing both change over time and final outcomes. PMID- 25132665 TI - Highly active macromolecular prodrugs inhibit expression of the hepatitis C virus genome in the host cells. AB - Efficacious, potent, and at the same time nontoxic macromolecular prodrugs of ribavirin are designed taking advantage over prodrug activation by the intracellular milieu. Activity of these prodrugs is illustrated in the cells hosting hepatitis C virus replication and also in the cells implicated in the inflammatory response to the viral infection. PMID- 25132666 TI - Cross-sectional evidence for a decrease in cognitive function with age in children with autism spectrum disorders? AB - Autism spectrum disorders (ASD) are associated with early disturbances in brain maturation processes and these interferences presumably have their consequences for the progressive emergence of cognitive deficits later in life, as expressed in intelligence profiles. In this study, we addressed the impact of age on cognitive functioning of 6- to 15-year-old children and adolescents with ASD. Intelligence profiles were measured by the Wechsler Intelligence Scale for Children and compared among four consecutive age cohorts (children aged 6.17-8.03 years, 8.04-9.61 years, and 9.68-11.50 years and adolescents aged 11.54-15.85 years) of 237 high-functioning boys with ASD. The results clearly demonstrated that the global intelligence level was lower in children aged 8 years and older, when compared with 6- and 7-year-old children with ASD. This is mostly due to the Freedom From Distractibility factor, suggesting that older children were less able to sustain their attention, they were more distractible, or had more graph motor difficulties. Moreover, an effect of age was also found with respect to the relatively poor performance on the subtest Comprehension when compared with other verbal comprehension subtests, indicating that specifically the impairments in verbal comprehension and social reasoning abilities were more profound in older children when compared with 6- and 7-year-old children with ASD. Findings of this cross-sectional study showed that it is relevant to take age into account when evaluating the impact of cognitive impairments on intelligence in children with ASD, because the impact of these developmental disorders might be different at different ages. PMID- 25132669 TI - Is the modified disease activity score superior to the disease activity score in early arthritis and rheumatoid arthritis? Comment on the article by Baker et al. PMID- 25132667 TI - Disease mechanisms in rheumatology--tools and pathways: defining functional genetic variants in autoimmune diseases. PMID- 25132670 TI - The use of dried blood spots for quantification of 15 antipsychotics and 7 metabolites with ultra-high performance liquid chromatography - tandem mass spectrometry. AB - Therapeutic drug monitoring of antipsychotics is important in optimizing individual therapy. In psychiatric populations, classical venous blood sampling is experienced as frightening. Interest in alternative techniques, like dried blood spots (DBS), has consequently increased. A fast and easy to perform DBS method for quantification of 16 antipsychotics (amisulpride, aripiprazole, asenapine, bromperidol, clozapine, haloperidol, iloperidone, levosulpiride, lurasidone, olanzapine, paliperidone, pipamperone, quetiapine, risperidone, sertindole and zuclopenthixol) and 8 metabolites was developed. DBS were prepared using 25 MUL of whole blood and extraction of complete spots was performed using methanol: methyl-t-butyl-ether (4:1). After evaporation, the extract was reconstituted in the mobile phase and 10 MUL were injected on an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Separation using a C18 column and gradient elution with a flow rate of 0.5 mL/min resulted in a 6-min run-time. Ionization was performed in positive mode and a dynamic MRM method was applied. Median recovery was 66.4 % (range 28.7-84.5%). Accuracy was within the acceptance criteria, except for pipamperone (LLOQ and low concentration) and lurasidone (low concentration). Imprecision was only aberrant for lurasidone at low and medium concentration. All compounds were stable during 1 month at room temperature, 4 degrees C and -18 degrees C. Lurasidone was unstable when the extract was stored for 12 h on the autosampler. Absolute matrix effects (ME) (median 66.1%) were compensated by the use of deuterated IS (median 98.8%). The DBS method was successfully applied on 25-MUL capillary DBS from patients and proved to be a reliable alternative for quantification of all antipsychotics except for olanzapine and N-desmethylolanzapine. PMID- 25132671 TI - Development of an autoimmune syndrome affecting the skin and internal organs in P selectin glycoprotein ligand 1 leukocyte receptor-deficient mice. AB - OBJECTIVE: To define and characterize the progression of the spontaneous autoimmune disease that develops in mice in the absence of the leukocyte adhesion receptor P-selectin glycoprotein ligand 1 (PSGL-1). METHODS: Skin-resident immune cells from PSGL-1-deficient mice and C57BL/6 control mice of different ages were isolated and analyzed by flow cytometry. Biochemical parameters were analyzed in mouse serum and urine, and the presence of serum autoantibodies was investigated. Skin and internal organs were extracted, and their structure was analyzed histologically. RESULTS: Skin-resident innate and adaptive immune cells from PSGL 1(-/-) mice had a proinflammatory phenotype with an imbalanced T effector cell:Treg cell ratio. Sera from PSGL-1(-/-) mice had circulating autoantibodies commonly detected in connective tissue-related human autoimmune diseases. Biochemical and histologic analysis of skin and internal organs revealed skin fibrosis and structural and functional abnormalities in the lungs and kidneys. Furthermore, PSGL-1(-/-) mice exhibited vascular alterations, showing loss of dermal vessels, small vessel medial layer remodeling in the lungs and kidneys, and ischemic processes in the kidney that promote renal infarcts. CONCLUSION: Our study demonstrates that immune system overactivation due to PSGL-1 deficiency triggers an autoimmune syndrome with characteristics similar to systemic sclerosis, including skin fibrosis, vascular alterations, and systemic organ involvement. These results suggest that PSGL-1 expression contributes to the maintenance of the homeostasis of the immune system and could act as a barrier for autoimmunity in mice. PMID- 25132673 TI - Reply: To PMID 24757132. PMID- 25132674 TI - Micro-scale blood particulate dynamics using a non-uniform rational B-spline based isogeometric analysis. AB - The current research presents a novel method in which blood particulates - biconcave red blood cells (RBCs) and spherical cells are modeled using isogeometric analysis, specifically Non-Uniform Rational B-Splines (NURBS) in 3 D. The use of NURBS ensures that even with a coarse representation, the geometry of the blood particulates maintains an accurate description when subjected to large deformations. The fundamental advantage of this method is the coupling of the geometrical description and the stress analysis of the cell membrane into a single, unified framework. Details on the modeling approach, implementation of boundary conditions and the membrane mechanics analysis using isogeometric modeling are presented, along with validation cases for spherical and biconcave cells. Using NURBS - based isogeometric analysis, the behavior of individual cells in fluid flow is presented and analyzed in different flow regimes using as few as 176 elements for a spherical cell and 220 elements for a biconcave RBC. This work provides a framework for modeling a large number of 3-D deformable biological cells, each with its own geometric description and membrane properties. To the best knowledge of the authors, this is the first application of the NURBS - based isogeometric analysis to model and simulate blood particulates in flow in 3D. PMID- 25132672 TI - Endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 1 targets misfolded HLA-B27 dimers for endoplasmic reticulum-associated degradation. AB - OBJECTIVE: HLA-B27 forms misfolded heavy chain dimers, which may predispose individuals to inflammatory arthritis by inducing endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). This study was undertaken to define the role of the UPR-induced ER-associated degradation (ERAD) pathway in the disposal of HLA-B27 dimeric conformers. METHODS: HeLa cell lines expressing only 2 copies of a carboxy-terminally Sv5-tagged HLA-B27 were generated. The ER stress-induced protein ER degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1) was overexpressed by transfection, and dimer levels were monitored by immunoblotting. EDEM1, the UPR-associated transcription factor X-box binding protein 1 (XBP-1), the E3 ubiquitin ligase hydroxymethylglutaryl-coenzyme A reductase degradation 1 (HRD1), and the degradation-associated proteins derlin 1 and derlin 2 were inhibited using either short hairpin RNA or dominant-negative mutants. The UPR-associated ERAD of HLA-B27 was confirmed using ER stress inducing pharamacologic agents in kinetic and pulse chase assays. RESULTS: We demonstrated that UPR-induced machinery can target HLA-B27 dimers and that dimer formation can be controlled by alterations to expression levels of components of the UPR-induced ERAD pathway. HLA-B27 dimers and misfolded major histocompatibility complex class I monomeric molecules bound to EDEM1 were detected, and overexpression of EDEM1 led to inhibition of HLA-B27 dimer formation. EDEM1 inhibition resulted in up-regulation of HLA-B27 dimers, while UPR-induced ERAD of dimers was prevented in the absence of EDEM1. HLA-B27 dimer formation was also enhanced in the absence of XBP-1, HRD1, and derlins 1 and 2. CONCLUSION: The present findings indicate that the UPR ERAD pathway can dispose of HLA-B27 dimers, thus presenting a potential novel therapeutic target for modulation of HLA-B27-associated inflammatory disease. PMID- 25132675 TI - Fibromyalgia syndrome and small-fiber neuropathy: comment on the article by Caro and Winter. PMID- 25132676 TI - Impact of complex blast waves on the human head: a computational study. AB - Head injuries due to complex blasts are not well examined because of limited published articles on the subject. Previous studies have analyzed head injuries due to impact from a single planar blast wave. Complex or concomitant blasts refer to impacts usually caused by more than a single blast source, whereby the blast waves may impact the head simultaneously or consecutively, depending on the locations and distances of the blast sources from the subject, their blast intensities, the sequence of detonations, as well as the effect of blast wave reflections from rigid walls. It is expected that such scenarios will result in more serious head injuries as compared to impact from a single blast wave due to the larger effective duration of the blast. In this paper, the utilization of a head-helmet model for blast impact analyses in Abaqus(TM) (Dassault Systemes, Singapore) is demonstrated. The model is validated against studies published in the literature. Results show that the skull is capable of transmitting the blast impact to cause high intracranial pressures (ICPs). In addition, the pressure wave from a frontal blast may enter through the sides of the helmet and wrap around the head to result in a second impact at the rear. This study recommended better protection at the sides and rear of the helmet through the use of foam pads so as to reduce wave entry into the helmet. The consecutive frontal blasts scenario resulted in higher ICPs compared with impact from a single frontal blast. This implied that blast impingement from an immediate subsequent pressure wave would increase severity of brain injury. For the unhelmeted head case, a peak ICP of 330 kPa is registered at the parietal lobe which exceeds the 235 kPa threshold for serious head injuries. The concurrent front and side blasts scenario yielded lower ICPs and skull stresses than the consecutive frontal blasts case. It is also revealed that the additional side blast would only significantly affect ICPs at the temporal and parietal lobes when compared with results from the single frontal blast case. By analyzing the pressure wave flow surrounding the head and correlating them with the consequential evolution of ICP and skull stress, the paper provides insights into the interaction mechanics between the concomitant blast waves and the biological head model. PMID- 25132677 TI - Reply: To PMID 24719395. PMID- 25132678 TI - Chronic rhinosinusitis patients have decreased lung function. AB - BACKGROUND: The relationship between upper and lower airway diseases has been reported. However, the pulmonary function of patients with chronic rhinosinusitis (CRS) has not been fully examined. METHODS: Pulmonary function was measured in 273 patients with CRS and 100 age-matched normal control subjects. No patients with chronic obstructive pulmonary disease (COPD) were included in this study. The patients with CRS were divided into 8 subgroups based on the presence of asthma, sensitization to common inhaled antigens, and nasal polyposis. The relationships between pulmonary function and clinical parameters, including radiographic severity of CRS according to the Lund-Mackay computed tomography (CT) staging system, eosinophil count in the peripheral blood, and serum total immunoglobulin E (IgE) levels, were assessed. RESULTS: In pulmonary function testing, the CRS patients had affected pulmonary function. The CRS patients without asthma showed latent obstructive pulmonary function changes when compared to normal controls. No significant correlations were observed between pulmonary function and any clinical parameters (Lund-Mackay CT staging score, eosinophil count in the peripheral blood, and serum total IgE levels). CONCLUSION: CRS patients had significant obstructive lung function changes regardless of the presence of asthma. The patients with CRS who had not been clinically diagnosed as having lower respiratory tract diseases might have had subclinical lower airway diseases. Therefore, clinicians should be aware of pulmonary function and lower lung diseases in patients with CRS. PMID- 25132679 TI - Regulation of cytokine polarization and T cell recruitment to inflamed paws in mouse collagen-induced arthritis by the chemokine receptor CXCR6. AB - OBJECTIVE: The chemokine receptor CXCR6 is highly expressed on lymphocytes isolated from the synovium of patients with rheumatoid arthritis, psoriatic arthritis, or juvenile idiopathic arthritis, suggesting that CXCR6 regulates immune cell activation or infiltration into arthritic joints. This study was undertaken to examine the role of CXCR6 in T cell activation and arthritis development. METHODS: A collagen-induced arthritis model was used to examine arthritis development in wild-type and CXCR6(-/-) mice. CXCR6 expression, lymphocyte accumulation, and intracellular cytokine production were examined by flow cytometry. Collagen-specific antibodies were measured in the serum. Collagen specific recall responses were examined in vitro via proliferation and cytokine release assays. T cell homing to inflamed joints was examined using competitive adoptive transfer of dye-labeled lymphocytes from wild-type and CXCR6(-/-) mice. RESULTS: The numbers of CXCR6+ T cells were increased in the paws and draining lymph nodes of arthritic mice. The incidence of arthritis, disease severity, extent of T cell accumulation, and levels of collagen-specific IgG2a antibodies were significantly reduced in CXCR6(-/-) mice compared to wild-type mice. T cells from wild-type mice exhibited Th1 (interferon-gamma [IFNgamma]) polarization in the inguinal lymph nodes following immunization. At disease peak, this shifted to a Th17 (interleukin-17A [IL-17A]) response in the popliteal lymph nodes. T cells in CXCR6(-/-) mice exhibited impaired cytokine polarization, resulting in a decreased frequency and number of IL-17A- and IFNgamma-producing cells. Recruitment of activated CXCR6(-/-) mouse T cells to the inflamed paws was impaired compared to recruitment of wild-type mouse T cells. CONCLUSION: These experiments demonstrate that CXCR6 plays important roles in the pathogenesis of arthritis through its effects on both T cell cytokine polarization and homing of T cells to inflamed joints. PMID- 25132680 TI - How does pharmacogenetic testing alter the treatment course and patient response for chronic-pain patients in comparison with the current "trial-and-error" standard of care? AB - PURPOSE: To evaluate if pharmacogenetic testing (PT) holds value for pain management practitioners by identifying the potential applications of pharmacogenetic research as well as applications in practice. DATA SOURCES: A review of the literature was conducted utilizing the databases EBSCOhost, Biomedical Reference Collection, CINAHL, Health Business: Full Text, Health Source: Nursing/Academic Edition, and MEDLINE with the keywords, personalized medicine, cytochrome P450, and phamacogenetics. CONCLUSIONS: Chronic-pain patients present some of the most challenging patients to manage medically. Often paired with persistent, life-altering pain, they might also have oncologic and psychological comorbidities that can further complicate their management. One step in-office PT is now widely available to optimize management of complicated patients and affectively remove the "trial-and-error" process of medication therapy. IMPLICATIONS FOR PRACTICE: Practitioners must be familiar with the genetic determinants that affect a patient's response to medications in order to decrease preventable morbidity and mortality associated with drug-drug and patient-drug interactions, and to provide cost-effective care through avoidance of inappropriate medications. Improved pain managements will impove patient outcomes and satisfaction. PMID- 25132682 TI - Collaborative arrangements for Australian nurse practitioners: a policy analysis. AB - PURPOSE: In Australia in 2010, nurse practitioners (NPs) were granted legislated access to the Medical Benefits Scheme (MBS) and Pharmaceutical Benefits Scheme (PBS) as providers. These schemes are the federal schemes for third-party reimbursement for health care and medications. As a condition of access to the schemes, it was determined that collaborative arrangements needed to be in place as part of eligibility criteria for NPs. This article is the first published policy analysis of this determination. DATA SOURCES: Published literature and available grey literature (including meeting minutes), and media content, was accessed and analyzed. CONCLUSIONS: The policy that was the National Health Collaborative arrangements for Nurse Practitioners Determination to amend the Australian National Health Act 1953 was a success. The policy led to NP access as providers to the MBS and PBS in Australia. IMPLICATIONS FOR PRACTICE: Understanding the policy process as it relates to the determination of the need for collaborative arrangements demystifies the process and origins of the policy for NPs in Australia. Understanding the determination means NPs in Australia will not artificially reduce scope of practice based on recommendations from the medical lobby. Clear research direction is provided that may inform the next policy cycle. PMID- 25132681 TI - Serum phytanic and pristanic acid levels and prostate cancer risk in Finnish smokers. AB - Phytanic acid is a saturated branched-chain fatty acid found predominantly in red meat and dairy products, and may contribute to the elevated risks of prostate cancer associated with higher consumption of these foods. Pristanic acid is formed during peroxisomal oxidation of phytanic acid, and is the direct substrate of alpha-Methyl-CoA-Racemase (AMACR)--an enzyme that is consistently overexpressed in prostate tumors relative to benign tissue. We measured phytanic and pristanic acids as percentages of total fatty acids by gas chromatography mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases and 300 matched controls, all of whom were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study supplementation trial and follow-up cohort. In addition to providing a fasting blood sample at baseline, all men completed extensive diet, lifestyle, and medical history questionnaires. Among controls, the strongest dietary correlates of serum phytanic and pristanic acids were saturated fat, dairy fat, and butter (r = 0.50 and 0.40, 0.46 and 0.38, and 0.40 and 0.37, respectively; all P-values <0.001). There was no association between serum phytanic acid and risk of total or aggressive prostate cancer in multivariate logistic regression models (for increasing quartiles, odds ratios (OR) and 95% confidence intervals (CI) for aggressive cancer were 1.0 (referent), 1.62 (0.97-2.68), 1.12 (0.66-1.90), and 1.14 (0.67-1.94), P(trend) = 0.87). Pristanic acid was strongly correlated with phytanic acid levels (r = 0.73, P < 0.0001), and was similarly unrelated to prostate cancer risk. Significant interactions between phytanic and pristanic acids and baseline circulating beta carotene concentrations were noted in relation to total and aggressive disease among participants who did not receive beta-carotene supplements as part of the original ATBC intervention trial. In summary, we observed no overall association between serum phytanic and pristanic acid levels and prostate cancer risk. Findings indicating that the direction and magnitude of these associations depended upon serum levels of the antioxidant beta-carotene among men not taking beta-carotene supplements should be interpreted cautiously, as they are likely due to chance. PMID- 25132684 TI - Ultrasound-guided fine-needle aspiration of a posterior neck dedifferentiated liposarcoma with MDM2 fluorescence in situ hybridization performed on a Pap stained smear. AB - Head and neck liposarcomas, while rare, tend to be subcutaneous and well differentiated. Dedifferentiated liposarcomas of the head and neck are exceedingly rare in the literature. We present a case of a dedifferentiated liposarcoma arising in the soft tissue of the posterior neck of an 86-year-old man and diagnosed by fine-needle aspiration. Aspirate smears showed a dual population of atypical lipomatous and spindled cells. MDM2 (murine double minute 2) amplification was demonstrated on a Pap-stained smear using fluorescence in situ hybridization (FISH). To the best of our knowledge, this is the first report of MDM2 FISH amplification in a liposarcoma performed on an aspirate smear. PMID- 25132683 TI - Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment. AB - Almost all highly metastatic tumor cells possess high platelet aggregating abilities, thereby form large tumor cell-platelet aggregates in the microvasculature. Embolization of tumor cells in the microvasculature is considered to be the first step in metastasis to distant organs. We previously identified the platelet aggregation-inducing factor expressed on the surfaces of highly metastatic tumor cells and named as Aggrus. Aggrus was observed to be identical to the marker protein podoplanin (alternative names, T1alpha, OTS-8, and others). Aggrus is frequently overexpressed in several types of tumors and enhances platelet aggregation by interacting with the platelet receptor C-type lectin-like receptor 2 (CLEC-2). Here, we generated a novel single-chain antibody variable region fragment (scFv) by linking the variable regions of heavy and light chains of the neutralizing anti-human Aggrus monoclonal antibody MS-1 with a flexible peptide linker. Unfortunately, the generated KM10 scFv failed to suppress Aggrus-induced platelet aggregation in vitro. Therefore, we performed phage display screening and finally obtained a high-affinity scFv, K-11. K-11 scFv was able to suppress Aggrus-induced platelet aggregation in vitro. Moreover, K-11 scFv prevented the formation of pulmonary metastasis in vivo. These results suggest that K-11 scFv may be useful as metastasis inhibitory scFv and is expected to aid in the development of preclinical and clinical examinations of Aggrus-targeted cancer therapies. PMID- 25132685 TI - Catalytic Activity of Ultrathin Pt Films on Aligned Carbon Nanotube Arrays. AB - Uniform ultrathin Pt films were electrodeposited onto an aligned array of carbon nanotubes (CNTs) for high-area chemically stable methanol fuel cell anodes. Electrochemical treatment of the graphitic CNT surfaces by diazoniumbenzoic acid allowed for uniform Pt electroplating. The mass activity of the Pt thin film can reach 400 A/g at a scan rate of 20 mV/s and in a solution of 1 M CH3OH/0.5 M H2SO4. A programmed pulse potential at 0V was also seen to nearly eliminate the effects of carbon monoxide poisoning. The mass activity of Pt for methanol oxidation can be maintained at 300 A/g for more than 3000 s, which is 19 times of that under a constant potential of 0.7 V (vs Ag/AgCl). PMID- 25132686 TI - The Role of Distal Variables in Behavior Change: Effects of Adolescents' Risk for Marijuana Use on Intention to Use Marijuana. AB - This study uses an integrative model of behavioral prediction as an account of adolescents' intention to use marijuana regularly. Adolescents' risk for using marijuana regularly is examined to test the theoretical assumption that distal variables affect intention indirectly. Risk affects intention indirectly if low risk and high-risk adolescents differ on the strength with which beliefs about marijuana are held, or if they differ on the relative importance of predictors of intention. A model test confirmed that the effect of risk on intention is primarily indirect. Adolescents at low and high risk particularly differed in beliefs concerning social costs and costs to self-esteem. Not surprisingly, at risk adolescents took a far more positive stand toward using marijuana regularly than did low-risk adolescents. On a practical level, the integrative model proved to be an effective tool for predicting intention to use marijuana, identifying key variables for interventions, and discriminating between target populations in terms of determinants of marijuana use. PMID- 25132687 TI - Dual Studies on a Hydrogen-Deuterium Exchange of Resorcinol and the Subsequent Kinetic Isotope Effect. AB - An efficient laboratory experiment has been developed for undergraduate students to conduct hydrogen-deuterium (H-D) exchange of resorcinol by electrophilic aromatic substitution using D2O and a catalytic amount of H2SO4. The resulting labeled product is characterized by 1H NMR. Students also visualize a significant kinetic isotope effect (kH/kD ~ 3 to 4) by adding iodine tincture to solutions of unlabeled resorcinol and the H-D exchange product. This method is highly adaptable to fit a target audience and has been successfully implemented in a pedagogical capacity with second-year introductory organic chemistry students as part of their laboratory curriculum. It was also adapted for students at the advanced high school level. PMID- 25132688 TI - Modeling Oral Reading Fluency Development in Latino Students: A Longitudinal Study Across Second and Third Grade. AB - This study examines growth in oral reading fluency across 2nd and 3rd grade for Latino students grouped in 3 English proficiency levels: students receiving English as a second language (ESL) services (n = 2,182), students exited from ESL services (n = 965), and students never designated as needing services (n = 1,857). An important focus was to learn whether, within these 3 groups, proficiency levels and growth were reliably related to special education status. Using hierarchical linear modeling, the authors compared proficiency levels and growth in oral reading fluency in English between and within groups and then to state reading benchmarks. Findings indicate that oral reading fluency scores reliably distinguished between students with learning disabilities and typically developing students within each group (effect sizes ranging from 0.96 to 1.51). The growth trajectory included a significant quadratic trend (generally slowing over time). These findings support the effectiveness of using oral reading fluency in English to screen and monitor reading progress under Response to Intervention models, but also suggest caution in interpreting oral reading fluency data as part of the process in identifying students with learning disabilities. PMID- 25132689 TI - Canalization of body size matters for lifetime reproductive success of male predatory mites (Acari: Phytoseiidae). AB - The adaptive canalization hypothesis predicts that highly fitness-relevant traits are canalized via past selection, resulting in low phenotypic plasticity and high robustness to environmental stress. Accordingly, we hypothesized that the level of phenotypic plasticity of male body size of the predatory mites Phytoseiulus persimilis (low plasticity) and Neoseiulus californicus (high plasticity) reflects the effects of body size variation on fitness, especially male lifetime reproductive success (LRS). We first generated small and standard-sized males of P. persimilis and N. californicus by rearing them to adulthood under limited and ample prey supply, respectively. Then, adult small and standard-sized males were provided with surplus virgin females throughout life to assess their mating and reproductive traits. Small male body size did not affect male longevity or the number of fertilized females but reduced male LRS of P. persimilis but not N. californicus. Proximately, the lower LRS of small than standard-sized P. persimilis males correlated with shorter mating durations, probably decreasing the amount of transferred sperm. Ultimately, we suggest that male body size is more strongly canalized in P. persimilis than N. californicus because deviation from standard body size has larger detrimental fitness effects in P. persimilis than N. californicus. PMID- 25132690 TI - Variable Selection in Generalized Functional Linear Models. AB - Modern research data, where a large number of functional predictors is collected on few subjects are becoming increasingly common. In this paper we propose a variable selection technique, when the predictors are functional and the response is scalar. Our approach is based on adopting a generalized functional linear model framework and using a penalized likelihood method that simultaneously controls the sparsity of the model and the smoothness of the corresponding coefficient functions by adequate penalization. The methodology is characterized by high predictive accuracy, and yields interpretable models, while retaining computational efficiency. The proposed method is investigated numerically in finite samples, and applied to a diffusion tensor imaging tractography data set and a chemometric data set. PMID- 25132691 TI - Multidimensional Screening and Methodology Development for Condensations Involving Complex 1,2-Diketones. AB - Multidimensional reaction screening employing complex 1,2-cycloheptanediones is described. The studies have enabled the discovery of regioselective, Lewis acid mediated condensations with substituted ureas and a diastereoselective hydrogenation process which proceeds via an interesting allylpalladium hydride isomerization. PMID- 25132692 TI - Alkylphenols in Surface Sediments of the Gulf of Gdansk (Baltic Sea). AB - The widespread use of alkylphenols in European industry has led to their presence in the environment and the living organisms of the Baltic Sea. The present study (2011-2012) was designed to determine the concentrations of alkylphenols, 4 nonylphenol (NP) and 4-tert-octylphenol (OP), in surface sediments of the Gulf of Gdansk, a section of the Baltic that lies in close proximity to industrial and agricultural areas and borders with an agglomeration of nearly one million inhabitants. It is also where the Vistula, the largest Polish river, ends its course. In spring, large concentrations of 4-nonylphenol and 4-tert-octylphenol were washed off into the coastal zone with meltwater. In summertime, sediments near the beach had the highest alkylphenol concentrations (NP-2.31 ng g-1 dw, OP 13.09 ng g-1 dw), which was related to tourism and recreational activity. In silt sediments located off the coast, the highest NP (1.46 ng g-1 dw) and OP (6.56 ng g-1 dw) amounts were observed in autumn. The origin of OP and NP at those test stations was linked to atmospheric transport of black carbon along with adsorbed alkylphenols. PMID- 25132693 TI - Sinorhizobium meliloti 1021 Exopolysaccharide as a Flocculant Improving Chromium(III) Oxide Removal from Aqueous Solutions. AB - Chromium(III) oxide is an amphoteric, dark green solid. This most stable dye is widely used in construction and ceramic industries as well as in painting. In this study, the attempt is made to determine flocculating properties of exopolysaccharide (EPS) synthesized by the bacteria Sinorhizobium meliloti 1021, which would increase the efficiency of chromium(III) oxide removal from sewages and wastewaters. The conditions under which EPS is the most effective destabilizing component of chromium(III) oxide suspension have been determined too. In order to characterize the structure of electric double layer formed at the solid/supporting electrolyte (EPS) solution interface, electrokinetic potential measurements and potentiometric titration were performed. The EPS amount adsorbed on the chromium(III) oxide surface as a solution pH function was also measured. Moreover, the stability of Cr2O3 suspension in the absence and presence of S. meliloti 1021 EPS was estimated. The pooled analysis of all obtained results showed that EPS causes chromium(III) oxide suspension destabilization in the whole examined pH range. The largest change in the system stability before and after the polymer addition was observed at pH 9. It is probable that under these conditions bridging flocculation occurs in the examined system. PMID- 25132694 TI - Coexistence of Legionella pneumophila Bacteria and Free-Living Amoebae in Lakes Serving as a Cooling System of a Power Plant. AB - The study was aimed at determining whether potentially pathogenic free-living amoebae (FLA) and Legionella pneumophila can be found in lakes serving as a natural cooling system of a power plant. Water samples were collected from five lakes forming the cooling system of the power plants Patnow and Konin (Poland). The numbers of investigated organisms were determined with the use of a very sensitive molecular method-fluorescence in situ hybridization (FISH). The result of the present study shows that thermally altered aquatic environments provide perfect conditions for the growth of L. pneumophila and amoebae. The bacteria were identified in the biofilm throughout the entire research period and in the subsurface water layer in July and August. Hartmanella sp. and/or Naegleria fowleri were identified in the biofilm throughout the entire research period. PMID- 25132695 TI - A Cognitive-Social Model of Fertility Intentions. AB - We examine the use and value of fertility intentions against the backdrop of theory and research in the cognitive and social sciences. First, we draw on recent brain and cognition research to contextualize fertility intentions within a broader set of conscious and unconscious mechanisms that contribute to mental function. Next, we integrate this research with social theory. Our conceptualizations suggest that people do not necessarily have fertility intentions; they form them only when prompted by specific situations. Intention formation draws on the current situation and on schemas of childbearing and parenthood learned through previous experience, imbued by affect, and organized by self-representation. Using this conceptualization, we review apparently discordant knowledge about the value of fertility intentions in predicting fertility. Our analysis extends and deepens existing explanations for the weak predictive validity of fertility intentions at the individual level and provides a social-cognitive explanation for why intentions predict as well as they do. When focusing on the predictive power of intentions at the aggregate level, our conceptualizations lead us to focus on how social structures frustrate or facilitate intentions and how the structural environment contributes to the formation of reported intentions in the first place. Our analysis suggests that existing measures of fertility intentions are useful but to varying extents and in many cases despite their failure to capture what they seek to measure. PMID- 25132696 TI - The Impact of School Connectedness and Teacher Support on Depressive Symptoms in Adolescents: A Multilevel Analysis. AB - Using data from Waves I and II of the National Longitudinal Study of Adolescent Health (Add Health), this study examined the association between school connectedness and teacher support and depressive symptoms in a weighted sample of 11,852 adolescents from 132 schools. To account for the nested data, multilevel regression was utilized. The results indicated higher school connectedness and getting along with teachers were significantly associated with fewer depressive symptoms. Findings offer implications for school social work practice and future research. Suggestions for future research are described and strategies to enhance school connectedness and teacher support are discussed. PMID- 25132697 TI - Complex Inequality: A Contextual Parenting Framework for Latino Infants. PMID- 25132698 TI - Are there meaningful individual differences in temporal inconsistency in self reported personality? AB - The current project had three goals. The first was to examine whether it is meaningful to refer to across-time variability in self-reported personality as an individual differences characteristic. The second was to investigate whether negative affect was associated with variability in self-reported personality, while controlling for mean levels, and correcting for measurement errors. The third goal was to examine whether variability in self-reported personality would be larger among young adults than among older adults, and whether the relation of variability with negative affect would be stronger at older ages than at younger ages. Two moderately large samples of participants completed the International Item Pool Personality questionnaire assessing the Big Five personality dimensions either twice or thrice, in addition to several measures of negative affect. Results were consistent with the hypothesis that within-person variability in self-reported personality is a meaningful individual difference characteristic. Some people exhibited greater across-time variability than others after removing measurement error, and people who showed temporal instability in one trait also exhibited temporal instability across the other four traits. However, temporal variability was not related to negative affect, and there was no evidence that either temporal variability or its association with negative affect varied with age. PMID- 25132700 TI - Using satellite remote sensing and household survey data to assess human health and nutrition response to environmental change. AB - Climate change and degradation of ecosystem services functioning may threaten the ability of current agricultural systems to keep up with demand for adequate and inexpensive food and for clean water, waste disposal and other broader ecosystem services. Human health is likely to be affected by changes occurring across multiple geographic and time scales. Impacts range from increasing transmissibility and the range of vectorborne diseases, such as malaria and yellow fever, to undermining nutrition through deleterious impacts on food production and concomitant increases in food prices. This paper uses case studies to describe methods that make use of satellite remote sensing and Demographic and Health Survey data to better understand individual-level human health and nutrition outcomes. By bringing these diverse datasets together, the connection between environmental change and human health outcomes can be described through new research and analysis. PMID- 25132699 TI - Collaborative Mother-Toddler Communication and Theory of Mind Development at Age 4. AB - Focusing on social pragmatics, this longitudinal study investigated the contribution of mother-toddler collaborative communication to theory of mind (ToM) development at age 4. At age 21/2, 78 toddlers' (42 boys) and their mothers were observed during pretend play. At age 4, children were tested using 4 false belief understanding tasks. Both mothers and toddlers engaged in more collaborative (inform, guide/request, and support/confirm) than non-collaborative communication acts. Other-focused collaborative acts of support/confirm by mothers and toddlers predicted children's false belief understanding, even after controlling for 5 covariates. In addition, as active agents in their own ToM development, the contribution of toddlers' collaborative acts to false belief understanding was independent of their mothers. Finally, the way toddlers and their mothers co-constructing their communication mattered. Only when toddlers engaged in high levels of collaborative acts, the mothers' high levels of collaborative acts demonstrated a positive effect on children's ToM development. The applied implications of these findings were discussed. PMID- 25132701 TI - Empirical research on international environmental migration: a systematic review. AB - This paper presents the findings of a systematic review of scholarly publications that report empirical findings from studies of environmentally-related international migration. There exists a small, but growing accumulation of empirical studies that consider environmentally-linked migration that spans international borders. These studies provide useful evidence for scholars and policymakers in understanding how environmental factors interact with political, economic and social factors to influence migration behavior and outcomes that are specific to international movements of people, in highlighting promising future research directions, and in raising important considerations for international policymaking. Our review identifies countries of migrant origin and destination that have so far been the subject of empirical research, the environmental factors believed to have influenced these migrations, the interactions of environmental and non-environmental factors as well as the role of context in influencing migration behavior, and the types of methods used by researchers. In reporting our findings, we identify the strengths and challenges associated with the main empirical approaches, highlight significant gaps and future opportunities for empirical work, and contribute to advancing understanding of environmental influences on international migration more generally. Specifically, we propose an exploratory framework to take into account the role of context in shaping environmental migration across borders, including the dynamic and complex interactions between environmental and non-environmental factors at a range of scales. PMID- 25132702 TI - Reassessing the Effects of Early Adolescent Alcohol Use on Later Antisocial Behavior: A Longitudinal Study of Students in Victoria, Australia and Washington State, United States. AB - The effect of early adolescent alcohol use on antisocial behavior was examined at one- and two-year follow-up in Washington, United States and Victoria, Australia. Each state used the same methods to survey statewide representative samples of students (N = 1,858, 52% female) in 2002 (Grade 7 [G7]), 2003 (Grade 8 [G8]), and 2004 (Grade 9 [G9]). Rates of lifetime, current, frequent, and heavy episodic alcohol use were higher in Victoria than Washington State, whereas rates of five antisocial behaviors were generally comparable across states. After controlling for established risk factors, few associations between alcohol use and antisocial behavior remained, except that G7 current use predicted G8 police arrests and stealing and G9 carrying a weapon and stealing; G7 heavy episodic use predicted G8 and G9 police arrests; and G7 lifetime use predicted G9 carrying a weapon. Hence, risk factors other than alcohol were stronger predictors of antisocial behaviors. PMID- 25132704 TI - Marine actinomycete Streptomyces sp. ISP2-49E, a new source of Rhamnolipid. PMID- 25132703 TI - Comparison of different blood collection, sample matrix, and immunoassay methods in a prenatal screening setting. AB - We compared how measurements of pregnancy-associated plasma protein A (PAPP-A) and the free beta subunit of human chorionic gonadotropin (fbeta-hCG) in maternal blood are influenced by different methods for blood collection, sample matrix, and immunoassay platform. Serum and dried blood spots (DBS) were obtained by venipuncture and by finger prick of 19 pregnant women. PAPP-A and fbeta-hCG from serum and from DBS were measured by conventional indirect immunoassay on an AutoDELFIA platform and by antibody microarray. We compared methods based on the recoveries for both markers as well as marker levels correlations across samples. All method comparisons showed high correlations for both marker concentrations. Recovery levels of PAPP-A from DBS were 30% lower, while those of fbeta-hCG from DBS were 50% higher compared to conventional venipuncture serum. The recoveries were not affected by blood collection or immunoassay method. The high correlation coefficients for both markers indicate that DBS from finger prick can be used reliably in a prenatal screening setting, as a less costly and minimally invasive alternative for venipuncture serum, with great logistical advantages. Additionally, the use of antibody arrays will allow for extending the number of first trimester screening markers on maternal and fetal health. PMID- 25132705 TI - Effect of initial conditions on reproducibility of scientific research. AB - BACKGROUND: It is estimated that about half of currently published research cannot be reproduced. Many reasons have been offered as explanations for failure to reproduce scientific research findings- from fraud to the issues related to design, conduct, analysis, or publishing scientific research. We also postulate a sensitive dependency on initial conditions by which small changes can result in the large differences in the research findings when attempted to be reproduced at later times. METHODS: We employed a simple logistic regression equation to model the effect of covariates on the initial study findings. We then fed the input from the logistic equation into a logistic map function to model stability of the results in repeated experiments over time. We illustrate the approach by modeling effects of different factors on the choice of correct treatment. RESULTS: We found that reproducibility of the study findings depended both on the initial values of all independent variables and the rate of change in the baseline conditions, the latter being more important. When the changes in the baseline conditions vary by about 3.5 to about 4 in between experiments, no research findings could be reproduced. However, when the rate of change between the experiments is <=2.5 the results become highly predictable between the experiments. CONCLUSIONS: Many results cannot be reproduced because of the changes in the initial conditions between the experiments. Better control of the baseline conditions in-between the experiments may help improve reproducibility of scientific findings. PMID- 25132706 TI - Sensitivity of EUS and ERCP Endoscopic Procedures in the Detection of Pancreatic Cancer During Preoperative Staging Correlated with CT and CT Angiography Imaging Methods. AB - THE GOAL: The goal of this work was to give advantage to EUS as endoscopic method in diagnosis and following therapeutic treatment of pancreatic cancer in relation to radiological methods of CT and CTA. MATERIAL AND METHODS: The study included 49 patients, 20 women and 29 men hospitalized at the Clinic for gastroenterohepatology, due to suspicion on pancreatic cancer during observed 2 years period. All cancers were histologically and cytologically confirmed. The patients underwent ERCP as a mandatory part of staging and all patients underwent endoscopic ultrasound as well as CT or CT angiography. RESULTS: Testing of differences was carried out using Fisher's exact test in open-source software R. The following characteristics were tested: involvement of the blood vessels, lymph nodes, metastases, tumor size and duodenum infiltration. Results showed statistically significant difference at the 0.05 level for EUS, CT and CT angiography. Risk ratio showed that EUS is less effective in detecting infiltration of blood vessels within a malignant process then CTA where RR=0.52, CI 0.2-1.38, p-value=0.33. EUS and CTA are equal in the diagnosis of enlarged lymph nodes affected by malignancy where RR=1.3, CI 0.75-1.42, p-value=0.09. Comparison according to distant metastases showed that EUS is less effective compared to CT in approximately 30% of cases. In the diagnosis of duodenal infiltration EUS is in 5% of cases less accurate than the CT with the RR=0.95, CI 0.27-3.32, p-value=0.76, but the CTA method is more efficient because the comparison of EUS and CTA showed RR=12.52, CI 0.2-1.38, p-value=0.33. EUS as a diagnostic method is dominant in determining the size of malignant lesions located in the pancreas as compared to CT and CTA. CONCLUSION: EUS as endoscopic method compared to CT and CTA is one of the more invasive methods of examination but due to its ability to be performed immediately, to locate a changes smaller than 5 mm and the target biopsy option, to measure the change and that in many cases determine the relationship of malignant lesions with blood vessels, along with visualization of the surrounding lymph nodes and metastases in neighboring organs, we may give this method an advantage over other methods in the preoperative staging of patients with pancreatic cancer. PMID- 25132707 TI - Colonoscopy as a method of choice in the diagnosis of colorectal cancer. AB - INTRODUCTION: Epidemiological characteristics of colorectal cancer indicate that in the U.S. colorectal cancer is the second leading cause of death from malignancy, just behind lung cancer. In the 2000 there were approximately 130,200 new cases, of which 56,300 had lethal outcome. In the past 15 years, the incidence and mortality rate has been declining, especially in women. Colorectal cancer is mainly found in people older than 50 years. Carcinoembryonic antigen (CEA) is insufficiently specific for the early detection of the disease. Its normal value is less than 5 g/L in the serum. Elevated levels of CEA after surgery indicate a lack of radical surgery, residual neoplasm, hidden distant metastases or recurrent disease. Unfortunately, only 10-15% of patients with recurrent disease can be successfully re-operated (isolated metastases in the liver or lungs). Colorectal cancer is predominantly adenocarcinoma, the tumor has relatively slow growth. While symptoms occur relatively early, distant metastases have relatively late appearance. GOALS: The goals of this study were to remind the fundamental facts about the nature of this disease, to stress the importance of early detection of BC-screening programs, to draw attention to contemporary attitudes in the field of diagnosis and treatment of colorectal cancer, and to show the experience in the treatment of this disease at the Surgical Departments of the General Hospital in Konjic. RESULTS: In the period from 2008-2012 years, at the Surgical Department of the General Hospital in Konjic surgically treated are 34 patients who had colorectal malignancy. There were 21 (65 %) male and 13 females (35%). All patients belonged to the age group of 50-75 years. Only five patients or 15 % prior to admission to the hospital had been diagnosed with a malignant process. All others, or 85% of the total sample, were admitted to the hospital as emergency cases (erosive gastritis), and after, shorter preparation underwent surgery. Only five (15%) of patients were admitted electively, already diagnosed with colorectal tumors by colonoscopy. Total number of lethal outcomes at the department was 8 (24%). Three patients died due to cardio-respiratory failure and MOF, and 5 patients due to anastomotic failure and septic shock. CONCLUSION: In conclusion we can say that in our institution it is necessary to obtain the proper equipment (colonoscope) and educate personnel, so we can introduce colonoscopy as the mandatory screening method of examination, particularly for vulnerable groups. PMID- 25132708 TI - Endoscopic management of vesicoureteral reflux in children in kosova. AB - INTRODUCTION: Vesicoureteral reflux (VUR) in children has been treated with subureteric deflux injection of Deflux (dextranomer hyaluronic acid copolymer) since 2009. The aim of this study was to analyze the results of endoscopic treatment of VUR in our clinic. METHODS: Between March 2009 and December 2013, fifty-five children underwent endoscopic subureteral injection of Deflux in 78 ureters. Two months postoperatively voiding cystourethrogram (VCUG) was performed. This study examined the disappearance of VUR and urinary tract infection (UTI) as well as the quality of life during long-term follow-up. RESULTS: The study included 55 patients (40 females and 15 males) with 78 refluxing ureters. There were 22 refluxed ureters altogether and 33 children had a unilateral reflux (two duplicated systems). All patients were treated, from the age 6 months up to 12 years old. The mean age of patients was 5.2 years. There has been no complications, but with few recurrences. In 6 patients (16.6%), endoscopic treatment with deflux was done twice, while in three patients (8.5%), the endoscopic treatment with deflux was performed three times, because of recurrence. CONCLUSION: We recommend the use of endoscopic Deflux injection as first line treatment for children with VUR. Endoscopic subureteral injection of Deflux is a minimally invasive method for VUR treatment in pediatric patients and is associated with low morbidity. PMID- 25132709 TI - Potential Role of Lung Ventilation Scintigraphy in the Assessment of COPD. AB - OBJECTIVE: To highlight the importance of the lung ventilation scintigraphy (LVS) to study the regional distribution of lung ventilation and to describe most frequent abnormal patterns of lung ventilation distribution obtained by this technique in COPD and to compare the information obtained by LVS with the that obtained by traditional lung function tests. MATERIAL AND METHODS: The research was done in 20 patients with previously diagnosed COPD who were treated in Intensive care unit of Clinic for pulmonary diseases and TB "Podhrastovi" Clinical Center, University of Sarajevo in exacerbation of COPD during first three months of 2014. Each patient was undergone to testing of pulmonary function by body plethysmography and ventilation/perfusion lung scintigraphy with radio pharmaceutics Technegas, 111 MBq Tc -99m-MAA. We compared the results obtained by these two methods. RESULTS: All patients with COPD have a damaged lung function tests examined by body plethysmography implying airflow obstruction, but LVS indicates not only airflow obstruction and reduced ventilation, but also indicates the disorders in distribution in lung ventilation. CONCLUSION: LVS may add further information to the functional evaluation of COPD to that provided by traditional lung function tests and may contribute to characterizing the different phenotypes of COPD. PMID- 25132710 TI - Importance of Alpha-adrenergic Receptor Subtypes in Regulating of Airways Tonus at Patients with Bronchial Asthma. AB - BACKGROUND: In this work, effect of Tamsulosin hydrochloride as antagonist of alpha1A and alpha1B- adrenergic receptor and effect of Salbutamol as agonist of beta2- adrenergic receptor in patients with bronchial asthma and increased bronchial reactibility was studied. METHODS: Parameters of the lung function are determined by Body plethysmography. Raw and ITGV were registered and specific resistance (SRaw) was also calculated. Tamsulosin was administered in per os way as a preparation in the form of the capsules with a brand name of "Prolosin", producer: Niche Generics Limited, Hitchin, Herts. RESULTS: Results gained from this research show that blockage of alpha1A and alpha1B- adrenergic receptor with Tamsulosin hydrochloride (0.4 mg and 0.8 mg in per os way) has not changed significantly (p > 0.1) the bronchomotor tonus of tracheobronchial tree in comparison to the inhalation of Salbutamol as agonist of beta2- adrenergic receptor (2 inh. x 0.2 mg), (p < 0.05). Arterial blood pressure showed no significant decrease following the administration of the dose of 0.8 mg Tamsulosin. CONCLUSION: This suggests that the activity of alpha1A and alpha1B- adrenergic receptor in the smooth musculature is not a primary mechanism which causes reaction in patients with increased bronchial reactibility, in comparison to agonists of beta2 - adrenergic receptor which emphasizes their significant action in the reduction of specific resistance of airways. PMID- 25132711 TI - A Survey on the Users' Satisfaction with the Hospital Information Systems (HISs) based on DeLone and McLean's Model in the Medical-Teaching Hospitals in Isfahan City. AB - BACKGROUND AND PURPOSE: The user's satisfaction with information system in fact denotes the extent the user is satisfied with the system's achievement in fulfilling his/her information requirements. This study tries to explore the users' satisfaction with hospital information systems (HISs) based on DeLone and McLean's model focusing on the medical-teaching hospitals of Isfahan city. METHODOLOGY: This study which was applied and descriptive-analytical in nature was carried out in the medical-teaching hospitals of Isfahan city in 2009. Research population consisted of the system users from which a sample was selected using random sampling method. The size of the sample was 228. Data collection instrument was a self-developed questionnaire produced based on the satisfaction criterion in the DeLone and McLean's model. Its content validity was assessed based on the opinions given by the computer sciences professionals with its estimated Cronbach's alpha found to be 92.2%. The data were analyzed using SPSS software. FINDINGS: As the findings of the study showed, the differences among the mean scores obtained for the satisfaction with different kinds of HISs in use in the hospitals were statistically significant (p value<=0.05). Generally, Kowsar System (old version) and Pouya Samaneh Diva system gained the highest and lowest mean scores for the criterion in question, respectively. The overall mean score for the satisfaction was 54.6% for different types of systems and 55.6% among the hospitals. CONCLUSION: Given the findings of the study, it can be argued that based on the used model, the level of users' satisfaction with the systems in question was relatively good. However, to achieve the total optimum condition, when designing the system, the factors affecting the enhancement of the users' satisfaction and the type of hospital activity and specialty must be given special consideration. PMID- 25132712 TI - Quality assessment of persian mental disorders websites using the webmedqual scale. AB - INTRODUCTION: Nowadays, anyone with any level of Internet knowledge can act as producer and distributor of information. It differs from most traditional media of information transmission, lack of information control and lack of quality management to contents. This leads to quality of health information on the internet is doubtful. The object of this study is guidance patients to select valid mental disorders and determine the quality of Persian mental disorders websites. METHODS: The sample of this study comprised 29 Persian mental disorders websites that were chosen by searching the Google, Yahoo and AltaVista search engines for the Persian equivalents of the three concepts "depression," "anxiety," and "obsession". website was created by individuals or organizations. Data collection was performed with the WebMedQual checklist. Websites was assessed based on indicators as content, authority of source, design, accessibility and availability, links, user support, and confidentiality and privacy (Maximum score for any website was 83, mean score 41.5 and minimum score was 0). Collected data analyzed by one sample T- test in SPSS 20. Findings presented by Mean score and optimal score. RESULTS: Based on the WebMedQual scale the mean score of Persian mental disorders websites in sex constructs including "content" (7.02+/-2.10), "authority of source" (4.71+/-1.96),"accessibility and availability" (2.19+/-0.47), "links" (1.45+/-0.97), "user support" (4.28+/-1.33), and"confidentiality and privacy" (2.81+/-2.81) are poor and below average, but the score for the "design" (9.17+/- 1.59) is above average. The best website of mental disorders was that of the "IranianPsychological Association". CONCLUSIONS: According to the results, only one website obtained the average score, so the quality of Persian mental disorders websites is low. Therefore, it is essential for users to criticize websites' content and not trust them before evaluating them. It is better to use the ranked list websites or search on the internet by help information experts. PMID- 25132713 TI - Medical universities educational and research online services: benchmarking universities' website towards e-government. AB - BACKGROUND: Websites as one of the initial steps towards an e-government adoption do facilitate delivery of online and customer-oriented services. In this study we intended to investigate the role of the websites of medical universities in providing educational and research services following the E-government maturity model in the Iranian universities. METHODS: This descriptive and cross- sectional study was conducted through content analysis and benchmarking the websites in 2012. The research population included the entire medical university website (37). Delivery of educational and research services through these university websites including information, interaction, transaction, and Integration were investigated using a checklist. The data were then analyzed by means of descriptive statistics and using SPSS software. RESULTS: Level of educational and research services by websites of the medical universities type I and II was evaluated medium as 1.99 and 1.89, respectively. All the universities gained a mean score of 1 out of 3 in terms of integration of educational and research services. CONCLUSIONS: Results of the study indicated that Iranian universities have passed information and interaction stages, but they have not made much progress in transaction and integration stages. Failure to adapt to e-government in Iranian medical universities in which limiting factors such as users' e literacy, access to the internet and ICT infrastructure are not so crucial as in other organizations, suggest that e-government realization goes beyond technical challenges. PMID- 25132714 TI - Scientific production of Sports Science in Iran: A Scientometric Analysis. AB - BACKGROUND: Physical education and sports science is one of the branches of humanities. The purpose of this study is determining the quantitative and qualitative rate of progress in scientific Production of Iran's researcher in Web of Science. METHODS: Research Methods is Scientometric survey and Statistical Society Includes 233 Documents From 1993 to 2012 are indexed in ISI. RESULTS: Results showed that the time of this study, Iranian researchers' published 233 documents in this base during this period of time which has been cited 1106(4.76 times on average). The H- index has also been 17. Iran's most scientific productions in sports science realm was indexed in 2010 with 57 documents and the least in 2000. CONCLUSIONS: By considering the numbers of citations and the obtained H- index, it can be said that the quality of Iranian's articles is rather acceptable but in comparison to prestigious universities and large number of professors and university students in this field, the quantity of outputted articles is very low. PMID- 25132715 TI - Contribution of Indian pediatric dentists to scientific literature during 2002 2012: a bibliometric analysis. AB - INTRODUCTION: Bibliometric analysis of publications is necessary to enable clinicians to make evidence based sound clinical decisions. It will also help policy makers & institutions to frame their decisions and policies so as to improve the quality of dental research in India. AIM: The purpose of this study is to identify publication output as well as descriptively and quantitatively characterize the contribution of Indian pediatric dentists to scientific literature through publication trend analysis from 2002 to 2012. SETTINGS AND DESIGN: Cross sectional analytical study. MATERIAL AND METHOD: A bibliometric analysis of publications by Indian pediatric dentists during 2002 to 2012 was performed on data collected from PubMed - MEDLINE database. Only the first author's affiliations were considered and the publications were categorized according to the following variables: year of publication, number of authors, state of origin, type of article, reach of journal and country of publication. RESULTS: There were 817 articles by Indian pediatric dentists during the study period. Of all the articles 399 (48.8%) were original research, 377(46.1%) were case reports and 41 (5.0%) were reviews. The inter-annual variation between the reach, country of publication of the journal and type of articles is presented. The growth trend analysis was performed and predictions are presented. CONCLUSION: There has been an increase in the number of publications by Indian pediatric dentists and most of the published work comprises of original research. The potential use of this data is discussed. PMID- 25132716 TI - Changes in the Muscle Strength of the Elbow Flexors Following a Six-week Experimental Procedure in Adolescents Monitored Through Isokinetic and Motor Tests. AB - A group of 7 subjects underwent an experimental procedure which studied the potential changes in the maximal strength of the non-dominant arm elbow flexors. The programme duration was limited to 6 weeks during which the subjects practiced exercises 3 times a week, 3 series, on a Scott bench. Individual approach was applied to the external load and it was designed so that the weight being lifted would increase if the number of lifts in one series would exceed 3. The subjects were monitored through the one-repetition maximum 1 RM motor test and the isokinetic tests performed on biodex system, tested in 3 time periods (at the beginning, after 3 weeks, and after the 6th week). Of the 6 isokinetic tests, only the test for the maximum torque and the time for achieving the maximum torque have shown statistically important changes in terms of reduction in values, which was not expected. The one-repetition maximum test, unlike the isokinetic tests, has shown statistically important increase of the maximal muscle strength of 32.1% after the third week of exercising, and 46.8% after the six weeks of exercising. The statistical test for the correlation between the two variables has shown low correlation between these two tests. The values of the data of the two test types have not shown any correspondence among the subjects possibly due to the type of performance of the maximal muscle load during exercises, performed in conditions identical to the one-repetition maximum test, with similar and yet different conditions in the case of isokinetic tests. Most probably, due to the conditions in which the exercises and the tests took place, there is difference in the obtained results. PMID- 25132717 TI - The Use of Smart phones in Ophthalmology. AB - Smart phones are being increasingly used among health professionals. Ophthalmological applications are widely available and can turn smart phones into sophisticated medical devices. Smart phones can be useful instruments for the practice of evidence-based medicine, professional education, mobile clinical communication, patient education, disease self-management, remote patient monitoring or as powerful administrative tools. Several applications are available for different ophthalmological examinations that can assess visual acuity, color vision, astigmatism, pupil size, Amsler grid test and more. Smart phones can be useful ophthalmic devices for taking images of anterior and posterior eye segment. Professional literature and educational material for patients are easily available with use of smart phones. Smart phones can store great amount of informations and are useful for long term monitoring with caution for patient confidentiality. The use of smart phones especially as diagnostic tools is not standardized and results should be carefully considered. Innovative role of smartphone technology and its use in research, education and information sharing makes smart phones a future of ophthalmology and medicine. PMID- 25132718 TI - EASE Guidelines for Authors and Translators of Scientific Articles to be Published in English. AB - This concise and readable set of editorial guidelines was first published by the European Association of Science Editors (EASE) in 2010 and is updated annually. It is freely available in more than 20 languages at http://ease.org.uk/publications/author-guidelines. The document is aimed to help scientists worldwide in successful presentation of their research results and in correct translation of manuscripts into English. Moreover, it draws attention to ethical issues, like authorship criteria, plagiarism, conflict of interests, etc. Eight appendices provide examples or more detailed information on selected topics (Abstracts, Ambiguity, Cohesion, Ethics, Plurals, Simplicity, Spelling, and Text tables). Widespread use of EASE Guidelines should increase the efficiency of international scientific communication. PMID- 25132719 TI - Enhanced Electro-Static Modulation of Ionic Diffusion through Carbon Nanotube Membranes by Diazonium Grafting Chemistry. AB - A membrane structure consisting of an aligned array of open ended carbon nanotubes (~ 7 nm i.d.) spanning across an inert polymer matrix allows the diffusive transport of aqueous ionic species through CNT cores. The plasma oxidation process that opens CNTs tips inherently introduces carboxylic acid groups at the CNT tips, which allows for a limited amount of chemical functional at the CNT pore entrance. However for numerous applications, it is important to increase the density of carboxylic acid groups at the pore entrance for effective separation processes. Aqueous diazonium based electro-chemistry significantly increases the functional density of carboxylic acid groups. pH dependent dye adsorption-desorption and interfacial capacitance measurements indicate ~ 5-6 times increase in functional density. To further control the spatial location of the functional chemistry, a fast flowing inert liquid column inside the CNT core is found to restrict the diazonium grafting to the CNT tips only. This is confirmed by the increased flux of positively charged Ru(bi-py)3+2 with anionic functionality. The electrostatic enhancement of ion diffusion is readily screened in 0.1(M) electrolyte solution consistent with the membrane pore geometry and increased functional density. PMID- 25132720 TI - Psychometric Evaluation of the Social Problem-Solving Inventory- Revised among Overweight or Obese Adults. AB - Problem solving is a key component of weight loss programs. The Social Problem Solving Inventory-Revised (SPSI-R) has not been evaluated in weight loss studies. The purpose of this study was to evaluate the psychometrics of the SPSI-R. Cronbach's alpha (.95 for total score; .67 - .92 for subscales) confirmed internal consistency reliability. The SPSI-R score was significantly associated (ps<.05) with decreased eating barriers and binge eating, increased self-efficacy in following a cholesterol-lowering diet, consumption of fewer calories and fat grams, more frequent exercise, lower psychological distress, and higher mental quality of life; all suggesting concurrent validity with other instruments used in weight loss studies. However, confirmatory factor analysis of the hypothesized 5-factor structure did not fit the data well (chi2=350, p<.001). PMID- 25132721 TI - Novel Method of Measuring Cantilever Deflection during an AFM Force Measurement. AB - A combination of a reflection interference contrast microscope (RICM) and the atomic force microscope (AFM) was used to monitor the cantilever-surface separation distance during force measurements using the streptavidin-biotin recognition pairs. The RICM showed that the cantilever loses contact with the surface before the final rupture of the adhesive bonds is measured by the AFM detection system. This finding suggests that the immobilization of biotin by physisorbed albumin and subsequent binding of streptavidin might have created a cross-linked protein network whose cohesion is tested by the AFM cantilever with the immobilized biotin ligands. PMID- 25132722 TI - Writing fluency and quality in kindergarten and first grade: The role of attention, reading, transcription, and oral language. AB - In the present study, we examined the influence of kindergarten component skills on writing outcomes, both concurrently and longitudinally to first grade. Using data from 265 students, we investigated a model of writing development including attention regulation along with students' reading, spelling, handwriting fluency, and oral language component skills. Results from structural equation modeling demonstrated that a model including attention was better fitting than a model with only language and literacy factors. Attention, a higher-order literacy factor related to reading and spelling proficiency, and automaticity in letter writing were uniquely and positively related to compositional fluency in kindergarten. Attention and higher-order literacy factor were predictive of both composition quality and fluency in first grade, while oral language showed unique relations with first grade writing quality. Implications for writing development and instruction are discussed. PMID- 25132723 TI - Abnormal Image Detection in Endoscopy Videos Using a Filter Bank and Local Binary Patterns. AB - Finding mucosal abnormalities (e.g., erythema, blood, ulcer, erosion, and polyp) is one of the most essential tasks during endoscopy video review. Since these abnormalities typically appear in a small number of frames (around 5% of the total frame number), automated detection of frames with an abnormality can save physician's time significantly. In this paper, we propose a new multi-texture analysis method that effectively discerns images showing mucosal abnormalities from the ones without any abnormality since most abnormalities in endoscopy images have textures that are clearly distinguishable from normal textures using an advanced image texture analysis method. The method uses a "texton histogram" of an image block as features. The histogram captures the distribution of different "textons" representing various textures in an endoscopy image. The textons are representative response vectors of an application of a combination of Leung and Malik (LM) filter bank (i.e., a set of image filters) and a set of Local Binary Patterns on the image. Our experimental results indicate that the proposed method achieves 92% recall and 91.8% specificity on wireless capsule endoscopy (WCE) images and 91% recall and 90.8% specificity on colonoscopy images. PMID- 25132724 TI - Feasibility of measuring antigen-antibody interaction forces using a scanning force microscope. AB - The molecular affinity scanning force microscopy (MASFM) described in this study was developed in an effort to test the possibility of antigen-antibody binding measurement using force-separation distance profiles. The MASFM configuration was comprised of a spherical glass bead as an MASFM probe, to which the fluorescein antigen has been covalently attached, and a silicon dioxide-based substrate, to which the antifluorescyl IgG antibody was covalently bound. The bead was glued to the tip of a commercial SFM cantilever. Adhesion forces have been measured between two different specific antigen-antibody pairs and between nonspecific surfaces bearing only glycidoxypropylsilane immobilization chemistry. In force separation (F-s) measurements, nonspecific forces displayed relatively few force discontinuities and mean adhesion forces lower than those found for specific antigen-antibody measurements. Force-separation profiles measured between specific antigen-antibody pairs showed many discontinuities and had higher mean forces. Positive controls revealed that the mean forces were slightly reduced by the addition of free ligand. The magnitude of mean forces did not correlate with the respective activation enthalpies of the proteins, as would be expected. At lower force values the force histograms for the specific pairs and for positive controls were indistinguishable. None of the force-separation data sets could fit a Poisson discrete-force model. This statistical analysis showed a large relative contribution from nonspecific interactions. It is concluded that the use of the large sphere as an SFM probe is counterproductive: while the large sphere does sample a larger number of specific interactions during each measurement, it also samples at the same time a large proportion of nonspecific forces. The presence of the nonspecific force contributions is likely due to the deformation of the polymerized GPS spacer layer which is thought to be delaminated from the surface upon the application of tension across the specific antigen-antibody bonds. PMID- 25132725 TI - The desorption of ribonuclease A from charge density gradient surfaces studied by spatially-resolved total internal reflection fluorescence. AB - A quaternary amine surface gradient was prepared on fused silica by a three-step surface modification process. The gradient surface displayed a transition of surface charges along the gradient dimension from a net negative surface charge of silica to a net positive surface charge at the quaternary amine end. The gradient surface was characterized by X-ray photoelectron spectroscopy, ellipsometry, colloidal gold decoration, and dynamic contact angle measurements. It displayed an increased adhesion of negatively charged gold particles towards the quaternary amine end. The water contact angles also increased with the increased surface density of aminopropylsilyl groups. The desorption of ribonuclease A labeled with fluorescein-5-isothiocyanate (FITC-RNase) from the quaternary amine gradient surface was measured using spatially resolved total internal reflection fluorescence (TIRF) spectroscopy. The experimental FITC-RNase desorption results fitted exceptionally well to a two adsorbed protein populations model. A tentative assignment of the two adsorbed protein populations is proposed based on the effect of the ionic strength of the desorbing buffer. The faster desorption population interacted primarily with the quaternary amine gradient surface sites through electrostatic interactions. The slower desorption population interacted with the surface sites via hydrophobic and possibly some electrostatic interactions. PMID- 25132726 TI - Chemical pattern on silica surface prepared by UV irradiation of 3 mercaptopropyltriethoxy silane layer: surface characterization and fibrinogen adsorption. AB - A flat silica surface modified with 3-mercaptopropyltriethoxy silane (MTS) was patterned using UV irradiation and a custom-designed mask. The irradiated surface was characterized by X-ray photoelectron spectroscopy (XPS), scanning force microscopy (SFM) and water contact angle measurements. The XPS S2p spectra indicated that the UV treatment resulted in the oxidation of MTS sulfur. The optimal UV irradiation dose for patterning, estimated from the XPS S2p binding energy shifts and water contact angles of irradiated surfaces, was 4.8 J cm-2 at 270 nm. The surface patterns were visualized by total internal reflection fluorescence microscopy, while exposing the pattern to a solution of acridine orange, by water vapor condensation, and by SFM lateral force imaging in dilute electrolyte solution. The adhesion SFM measurements revealed the adhesion force only on the areas which were not UV-irradiated. The adsorption of fluorescein labeled fibrinogen (FITC-Fgn) from dilute buffer solution also produced visual information on the pattern. The kinetics of FITC-Fgn adsorption onto the oxidized and unoxidized MTS-silica surfaces from dilute protein solution proceeded with identical initial adsorption rates. The steady-state FITC-Fgn adsorption was twice as large on the unoxidized MTS-silica than on the oxidized MTS-silica surface. PMID- 25132727 TI - Maternal Social Coaching Quality Interrupts the Development of Relational Aggression During Early Childhood. AB - Previous research has shown that parents of socially competent young children provide them with elaborative, explicit, appropriate and emotion-laden advice about peer interactions. The current study analyzed mothers' conversations with preschoolers (N=175; 52% female; M age = 52 months, SD = 7 months) about peer conflicts involving relational aggression. Conversations were coded for maternal elaboration, emotion references, and discussion of norm violations. Information about relational and physical aggression was collected from teachers at two assessments approximately 12 months apart for a subsample of 136 children. Regression analyses, controlling for physical aggression, showed that average and high levels of effective coaching operated as a protective factor against stable high levels of relational aggression. Theoretical and practical implications for our understanding of the early development of relational aggression are discussed. PMID- 25132728 TI - YKL-40 as a novel factor associated with inflammation and catabolic mechanisms in osteoarthritic joints. AB - YKL-40 is associated with tissue injury and inflammation, and consequently to diseases in which these mechanisms lead to tissue degradation, for example, asthma and rheumatoid arthritis. The purpose of the present study was to investigate if YKL-40 is also a significant factor in osteoarthritis (OA) by assessing associations of YKL-40 with mediators related to the pathogenesis of OA: cartilage destructing matrix metalloproteinases (MMPs) and proinflammatory cytokines interleukin-6 (IL-6) and interleukin-17 (IL-17). Cartilage, synovial fluid (SF), and plasma samples were obtained from 100 OA patients undergoing total knee replacement surgery. SF levels of YKL-40 (1027.9 +/- 78.3 ng/mL) were considerably higher than plasma levels (67.2 +/- 4.5 ng/mL) and correlated with YKL-40 released from cartilage samples obtained from the same patients (r = 0.37, P = 0.010), indicating that YKL-40 is produced by OA cartilage. Interestingly, YKL-40 concentrations in OA SF correlated positively with MMP-1 (r = 0.36, P = 0.014), MMP-3 (r = 0.46, P = 0.001), IL-6 (r = 0.57, P < 0.001), and IL-17 (r = 0.52, P = 0.010) levels. Moreover, IL-6 and IL-17 enhanced YKL-40 production in human primary chondrocyte cultures. The present study introduces YKL-40 as a cartilage-derived factor associated with mediators of inflammation and cartilage destruction involved in the pathogenesis of OA. PMID- 25132729 TI - Relationship between early inflammatory response and clinical evolution of the severe multiorgan failure in mechanical circulatory support-treated patients. AB - BACKGROUND: The mechanical circulatory support (MCS) is an effective treatment in critically ill patients with end-stage heart failure (ESHF) that, however, may cause a severe multiorgan failure syndrome (MOFS) in these subjects. The impact of altered inflammatory response, associated to MOFS, on clinical evolution of MCS postimplantation patients has not been yet clarified. METHODS: Circulating cytokines, adhesion molecules, and a marker of monocyte activation (neopterin) were determined in 53 MCS-treated patients, at preimplant and until 2 weeks. MOFS was evaluated by total sequential organ failure assessment score (tSOFA). RESULTS: During MCS treatment, 32 patients experienced moderate MOFS (tSOFA < 11; A group), while 21 patients experienced severe MOFS (tSOFA >= 11) with favorable (B group) or adverse (n = 13, C group) outcomes. At preimplant, higher values of left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were the only parameter independently associated with A group. In C group, during the first postoperative week, high levels of interleukin-8 (IL-8) and tumor necrosis factor (TNF)-alpha, and an increase of neopterin and adhesion molecules, precede tSOFA worsening and exitus. CONCLUSIONS: The MCS patients of C group show an excessive release to IL-8 and TNF-alpha, and monocyte-endothelial activation after surgery, that might contribute to the unfavourable evolution of severe MOFS. PMID- 25132730 TI - Macrophage trafficking as key mediator of adenine-induced kidney injury. AB - Macrophages play a special role in the onset of several diseases, including acute and chronic kidney injuries. In this sense, tubule interstitial nephritis (TIN) represents an underestimated insult, which can be triggered by different stimuli and, in the absence of a proper regulation, can lead to fibrosis deposition. Based on this perception, we evaluated the participation of macrophage recruitment in the development of TIN. Initially, we provided adenine-enriched food to WT and searched for macrophage presence and action in the kidney. Also, a group of animals were depleted of macrophages with the clodronate liposome while receiving adenine-enriched diet. We collected blood and renal tissue from these animals and renal function, inflammation, and fibrosis were evaluated. We observed higher expression of chemokines in the kidneys of adenine-fed mice and a substantial protection when macrophages were depleted. Then, we specifically investigated the role of some key chemokines, CCR5 and CCL3, in this TIN experimental model. Interestingly, CCR5 KO and CCL3 KO animals showed less renal dysfunction and a decreased proinflammatory profile. Furthermore, in those animals, there was less profibrotic signaling. In conclusion, we can suggest that macrophage infiltration is important for the onset of renal injury in the adenine induced TIN. PMID- 25132731 TI - Oral administration of herbal mixture extract inhibits 2,4-dinitrochlorobenzene induced atopic dermatitis in BALB/c mice. AB - CP001 is four traditional herbal medicine mixtures with anti-inflammatory properties. In this study, we investigated the effect of oral administration of CP001 ethanol extract on the 2,4-dinitrochlorobenzene- (DNCB-) induced AD mouse models. For that purpose, we observed the effects of oral administration of CP001 on skin inflammatory cell infiltration, skin mast cells, production of serum IgE, and expression of Th2 cytokine mRNA in the AD skin lesions of DNCB treated BALB/c mice. Histological analyses demonstrated that CP001 decreased dermis and epidermis thickening as well as dermal infiltration induced by inflammatory cells. In addition, CP001 decreased mast cell infiltration in count as well as dermal infiltration induced by inflammatory cells. In the skin lesions, mRNA expression of interleukin- (IL-) 4 and IL-13 was inhibited by CP001. CP001 also reduced the production of IgE level in mouse plasma. In addition, we investigated the effect of CP001 on the inflammatory allergic reaction using human mast cells (HMC-1). In HMC-1, cytokine production and mRNA levels of IL-4, IL-13, IL-6, and IL-8 were suppressed by CP001. Taken together, our results showed that oral administration of CP001 exerts beneficial effects in AD symptoms, suggesting that CP001 might be a useful candidate for the treatment of AD. PMID- 25132735 TI - Circumsporozoite protein-specific K(d)-restricted CD8+ T cells mediate protective antimalaria immunity in sporozoite-immunized MHC-I-K(d) transgenic mice. AB - Although the roles of CD8+ T cells and a major preerythrocytic antigen, the circumsporozoite (CS) protein, in contributing protective antimalaria immunity induced by radiation-attenuated sporozoites, have been shown by a number of studies, the extent to which these players contribute to antimalaria immunity is still unknown. To address this question, we have generated C57BL/6 (B6) transgenic (Tg) mice, expressing K(d) molecules under the MHC-I promoter, called MHC-I-K(d)-Tg mice. In this study, we first determined that a single immunizing dose of IrPySpz induced a significant level of antimalaria protective immunity in MHC-I-K(d)-Tg mice but not in B6 mice. Then, by depleting various T-cell subsets in vivo, we determined that CD8+ T cells are the main mediator of the protective immunity induced by IrPySpz. Furthermore, when we immunized (MHC-I-K(d)-Tg * CS Tg) F1 mice with IrPySpz after crossing MHC-I-K(d)-Tg mice with PyCS-transgenic mice (CS-Tg), which are unable to mount PyCS-specific immunity, we found that IrPySpz immunization failed to induce protective antimalaria immunity in (MHC-I K(d)-Tg * CS-Tg) F1 mice, thus indicating the absence of PyCS antigen-dependent immunity in these mice. These results indicate that protective antimalaria immunity induced by IrPySpz in MHC-I-K(d)-Tg mice is mediated by CS protein specific, K(d)-restricted CD8+ T cells. PMID- 25132732 TI - Purinergic receptors in ocular inflammation. AB - Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly "tuned," can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P(1),P(4)-diadenosine tetraphosphate (Ap4A), and P(1),P(5)-diadenosine pentaphosphate (Ap5A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (CF101) have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases) can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation. PMID- 25132734 TI - Endocan levels in peripheral blood predict outcomes of acute respiratory distress syndrome. AB - PURPOSE: To investigate the prognostic significance of endocan, compared with procalcitonin (PCT), C-reactive protein (CRP),white blood cells (WBC), neutrophils (N), and clinical severity scores in patients with ARDS. METHODS: A total of 42 patients with ARDS were initially enrolled, and there were 20 nonsurvivors and 22 survivors based on hospital mortality. Plasma levels of biomarkers were measured and the acute physiology and chronic health evaluation II (APACHE II) was calculated on day 1 after the patient met the defining criteria of ARDS. RESULTS: Endocan levels significantly correlated with the APACHE II score in the ARDS group (r = 0.676, P = 0.000, n = 42). Of 42 individuals with ARDS, 20 were dead, and endocan was significantly higher in nonsurvivors than in survivors (median (IQR) 5.01 (2.98-8.44) versus 3.01 (2.36 4.36) ng/mL, P = 0.017). According to the results of the ROC-curve analysis and COX proportional hazards models, endocan can predict mortality of ARDS independently with a hazard ratio of 1.374 (95% CI, 1.150-1.641) and an area of receiver operator characteristic curve (AUROC) of 0.715 (P = 0.017). Moreover, endocan can predict the multiple-organ dysfunction of ARDS. CONCLUSION: Endocan is a promising biomarker to predict the disease severity and mortality in patients with ARDS. PMID- 25132736 TI - Intestinal mucosal barrier is injured by BMP2/4 via activation of NF-kappaB signals after ischemic reperfusion. AB - Intestinal ischemic reperfusion (I/R) can cause dysfunction of the intestinal mucosal barrier; however, the mechanism of the intestinal mucosal barrier dysfunction caused by I/R remains unclear. In this study, using intestinal epithelial cells under anaerobic cultivation and an in vivo rat intestinal I/R model, we found that hypoxia and I/R increased the expression of BMP2/4 and upregulated BMP type Ia receptor and BMP type II receptor expression. We also found that exogenous BMP2/4 can activate the ERK and AKT signaling pathways in rat small intestine (IEC-6) cells, thereby activating NF-kappaB signaling, which leads to increased levels of inflammatory factors, such as TNF-alpha and IL-6. Furthermore, recombinant BMP2/4 decreased the expression of the tight junction protein occludin via the activation of the NF-kappaB pathway; these effects were abolished by treatment with the BMP-specific antagonist noggin or the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC). All these factors can destroy the intestinal mucosal barrier, thereby leading to weaker barrier function. On the basis of these data, we conclude that BMP2/4 may act as the pathogenic basis for intestinal mucosal barrier dysfunction when the intestines suffer an I/R injury. Our results provide background for the development pharmacologic interventions in the management of I/R injury. PMID- 25132738 TI - Diagnostics for Statistical Variable Selection Methods for Prediction of Peptic Ulcer Disease in Helicobacter pylori Infection. AB - BACKGROUND: The development of accurate classification models depends upon the methods used to identify the most relevant variables. The aim of this article is to evaluate variable selection methods to identify important variables in predicting a binary response using nonlinear statistical models. Our goals in model selection include producing non-overfitting stable models that are interpretable, that generate accurate predictions and have minimum bias. This work was motivated by data on clinical and laboratory features of Helicobacter pylori infections obtained from 60 individuals enrolled in a prospective observational study. RESULTS: We carried out a comprehensive performance comparison of several nonlinear classification models over the H. pylori data set. We compared variable selection results by Multivariate Adaptive Regression Splines (MARS), Logistic Regression with regularization, Generalized Additive Models (GAMs) and Bayesian Variable Selection in GAMs. We found that the MARS model approach has the highest predictive power because the nonlinearity assumptions of candidate predictors are strongly satisfied, a finding demonstrated via deviance chi-square testing procedures in GAMs. CONCLUSIONS: Our results suggest that the physiological free amino acids citrulline, histidine, lysine and arginine are the major features for predicting H. pylori peptic ulcer disease on the basis of amino acid profiling. PMID- 25132733 TI - Role of microglia adenosine A(2A) receptors in retinal and brain neurodegenerative diseases. AB - Neuroinflammation mediated by microglial cells in the brain has been commonly associated with neurodegenerative diseases. Whether this microglia-mediated neuroinflammation is cause or consequence of neurodegeneration is still a matter of controversy. However, it is unequivocal that chronic neuroinflammation plays a role in disease progression and halting that process represents a potential therapeutic strategy. The neuromodulator adenosine emerges as a promising targeting candidate based on its ability to regulate microglial proliferation, chemotaxis, and reactivity through the activation of its G protein coupled A2A receptor (A2AR). This is in striking agreement with the ability of A2AR blockade to control several brain diseases. Retinal degenerative diseases have been also associated with microglia-mediated neuroinflammation, but the role of A2AR has been scarcely explored. This review aims to compare inflammatory features of Parkinson's and Alzheimer's diseases with glaucoma and diabetic retinopathy, discussing the therapeutic potential of A2AR in these degenerative conditions. PMID- 25132739 TI - Endoscopic ultrasound and paracentesis in the evaluation of small volume ascites in patients with intra-abdominal malignancies. AB - The evaluation of ascites in patients with known or suspected malignancy is a critical aspect of preoperative staging. Endoscopic evaluation by ultrasound of low volume ascites and sampling of the ascitic fluid by endoscopic ultrasound guided paracentesis (EUS-P) is both a sensitive and specific modality for the determination of peritoneal implants, which is not only an important prognostic indicator but a crucial factor in determining treatment strategy. It is common practice to utilize EUS for gastrointestinal malignancies such as pancreatic or gastric masses, with the performance of paracentesis during the same procedure for the purpose of imaging the abnormality and possibly performing fine needle aspiration for biopsy of the neoplasm itself. However, given the ability of EUS-P to adequately sample even minimal ascites, detecting much smaller volumes than traditional computed tomography or magnetic resonance imaging, EUS-P may be a useful modality for the standard metastatic workup of any newly diagnosed or suspected malignancy. In this "Field of Vision" commentary, we discuss the role of EUS-P, including the article by Suzuki et al reporting their experience with EUS-P using an automated spring-loaded needle device. We also review the utility of EUS-P for non-gastrointestinal malignancies, such as ovarian cancer, which has a high incidence of malignant ascites. PMID- 25132737 TI - Untangling the web of systemic autoinflammatory diseases. AB - The innate immune system is involved in the pathophysiology of systemic autoinflammatory diseases (SAIDs), an enlarging group of disorders caused by dysregulated production of proinflammatory cytokines, such as interleukin-1beta and tumor necrosis factor-alpha, in which autoreactive T-lymphocytes and autoantibodies are indeed absent. A widely deranged innate immunity leads to overactivity of proinflammatory cytokines and subsequent multisite inflammatory symptoms depicting various conditions, such as hereditary periodic fevers, granulomatous disorders, and pyogenic diseases, collectively described in this review. Further research should enhance our understanding of the genetics behind SAIDs, unearth triggers of inflammatory attacks, and result in improvement for their diagnosis and treatment. PMID- 25132740 TI - Current management of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis. Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system. The choice among therapeutic options that include liver resection, liver transplantation, locoregional, and systemic treatments must be individualized for each patient. The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice. PMID- 25132741 TI - Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the leading causes of death induced by cancer in the modern world and majority of the cases are related to chronic hepatitis B virus (HBV) infection. HBV-encoded X protein (HBx) is known to play a pivotal role in the pathogenesis of viral induced HCC. HBx is a multifunctional protein of 17 kDa which modulates several cellular processes by direct or indirect interaction with a repertoire of host factors resulting in HCC. HBX might interfere with several cellular processes such as oxidative stress, DNA repair, signal transduction, transcription, protein degradation, cell cycle progression and apoptosis. A number of reports have indicated that HBx is one of the most common viral ORFs that is often integrated into the host genome and its sequence variants play a crucial role in HCC. By mutational or deletion analysis it was shown that carboxy terminal of HBx has a likely role in protein-protein interactions, transcriptional transactivation, DNA repair, cell, signaling and pathogenesis of HCC. The accumulated evidence thus far suggests that it is difficult to understand the mechanistic nature of HBx associated HCC, and HBx mediated transcriptional transactivation and signaling pathways may be a major determinant. This article addresses the role of HBx in the development of HCC with particular emphasis on HBx mutants and their putative targets. PMID- 25132742 TI - Implications of biomarkers in human hepatocellular carcinoma pathogenesis and therapy. AB - Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide and accounts for approximately one-third of all malignancies. In the past decade, advances have been made to improve the prognosis of HCC, including improvement in the clinical diagnosis of early-stage HCC using molecular biomarkers and molecular-targeted therapy to treat advanced HCC. However, the diagnosis, pathogenesis and targeted therapy of HCC are not completely independent, and should be comprehensively studied. For example, a number of tumor markers provide useful clinical information not only for prognosis, but also in pathogenesis and treatment efficacy. Therefore, this review will focus on the role of several specific biomarkers implicated in the pathogenesis of HCC and several promising molecular-targeted drugs that target the biomarkers of HCC. PMID- 25132745 TI - Rationally designed treatment for metastatic colorectal cancer: current drug development strategies. AB - The therapeutic landscape of metastatic colorectal cancer (mCRC) has changed substantially with the emergence of new molecularly targeted agents (MTA) used as single agents or alongside standard chemotherapy. The use of these MTAs extended the overall survival of patients with mCRC to a level that current chemotherapeutics alone could not achieve. In addition, improvement in surgical techniques and ablation modalities offer cure to a limited subset of patients with mCRC and MTAs have been found to have a significant role here too, as they aid resectability. However, for the majority of patients, mCRC remains an invariably incurable disease necessitating continued courses of combined treatment modalities. During the course of these treatments, either cytotoxic or biological, cancer cells maintain their ability to acquire mitogenic mutations which render them resistant to treatment. Key challenges remain to identify appropriate subsets of patients who will most likely benefit from these new MTAs and effectively select these based on validated biomarkers. Moreover, better knowledge of the biology of colorectal cancer and the mechanisms via which it bypasses blockade of known signalling pathways will help us design better and more rational sequencing of these treatments, so that we can maximise the survivorship of mCRC patients. This review outlines treatment strategies for known molecular alterations with new MTAs and highlights some promising strategies. PMID- 25132744 TI - STAT3 and sphingosine-1-phosphate in inflammation-associated colorectal cancer. AB - Accumulated evidences have demonstrated that signal transducer and activator of transcription 3 (STAT3) is a critical link between inflammation and cancer. Multiple studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer (CRC) is associated with sphingosine-1-phosphate (S1P) receptor signaling. In inflammatory response whereby interleukin (IL)-6 production is abundant, STAT3-mediated pathways were found to promote the activation of sphingosine kinases (SphK1 and SphK2) leading to the production of S1P. Reciprocally, S1P encourages the activation of STAT3 through a positive autocrine-loop signaling. The crosstalk between IL-6, STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed intestines. Therapeutics targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC. PMID- 25132743 TI - Inflammatory bowel disease in pediatric and adolescent patients: a biomolecular and histopathological review. AB - Crohn's disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD) with both overlapping and distinct clinical, pathological and biomolecular features. It has been suggested that pediatric IBD is a distinct disease entity, with probably different disease subtypes.The aim of this study is to review and summarize the evolution of the current concept of pediatric IBD. The results of this review reinforce the idea that pediatric CD and UC may be further classified in various clinicopathologic entities. For clinicians and pathologists convenience, practical algorithms for the distinction of the various subphenotypes of pediatric IBD are also provided. PMID- 25132746 TI - Prognostic relevance of minimal residual disease in colorectal cancer. AB - Presence of occult minimal residual disease in patients with colorectal cancer (CRC) has a strong prognostic impact on survival. Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC. Analysis of circulating tumor cells (CTC) in the blood is increasingly used in clinical practice for disease monitoring of CRC patients. In this review article the role of CTC, disseminated tumor cells (DTC) in the bone marrow and micrometastases and isolated tumor cells (ITC) in the lymph nodes will be discussed, including literature published until September 2013. Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood, DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes. Minimal residual disease could be used in the future to identify patient groups at risk, who might benefit from individualized treatment options. PMID- 25132747 TI - Bowman-Birk inhibitors from legumes as colorectal chemopreventive agents. AB - Aberrant functioning of serine proteases in inflammatory and carcinogenic processes within the gastrointestinal tract (GIT) has prompted scientists to investigate the potential of serine protease inhibitors, both natural and synthetic, as modulators of their proteolytic activities. Protease inhibitors of the Bowman-Birk type, a major protease inhibitor family in legume seeds, which inhibit potently and specifically trypsin- and chymotrypsin-like proteases, are currently being investigated as colorectal chemopreventive agents. Physiologically relevant amounts of Bowman-Birk inhibitors (BBI) can reach the large intestine in active form due to their extraordinary resistance to extreme conditions within the GIT. Studies in animal models have proven that dietary BBI from several legume sources, including soybean, pea, lentil and chickpea, can prevent or suppress carcinogenic and inflammatory processes within the GIT. Although the therapeutic targets and the action mechanism of BBI have not yet been elucidated, the emerging evidence suggests that BBI exert their preventive properties via protease inhibition; in this sense, serine proteases should be considered as primary targets in early stages of carcinogenesis. The validation of candidate serine proteases as therapeutic targets together with the identification, within the wide array of natural BBI variants, of the most potent and specific protease inhibitors, are necessary to better understand the potential of this protein family as colorectal chemopreventive agents. PMID- 25132749 TI - Helicobacter pylori infection and drugs malabsorption. AB - Drug absorption represents an important factor affecting the efficacy of oral drug treatment. Gastric secretion and motility seem to be critical for drug absorption. A causal relationship between impaired absorption of orally administered drugs and Helicobacter pylori (H. pylori) infection has been proposed. Associations have been reported between poor bioavailability of l thyroxine and l-dopa and H. pylori infection. According to the Maastricht Florence Consensus Report on the management of H. pylori infection, H. pylori treatment improves the bioavailability of both these drugs, whereas the direct clinical benefits to patients still await to be established. Less strong seems the association between H. pylori infection and other drugs malabsorption, such as delavirdine and ketoconazole. The exact mechanisms forming the basis of the relationship between H. pylori infection and impaired drugs absorption and/or bioavailability are not fully elucidated. H. pylori infection may trigger a chronic inflammation of the gastric mucosa, and impaired gastric acid secretion often follows. The reduction of acid secretion closely relates with the wideness and the severity of the damage and may affect drug absorption. This minireview focuses on the evidence of H. pylori infection associated with impaired drug absorption. PMID- 25132748 TI - FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy. AB - While 5-fluorouracil used as single agent in patients with metastatic colorectal cancer has an objective response rate around 20%, the administration of combinations of irinotecan with 5-fluorouracil/folinic acid or oxaliplatin with 5 fluorouracil/folinic acid results in significantly increased response rates and improved survival. However, the side effects of systemic therapy such as myelotoxicity, neurotoxicity or gastrointestinal toxicity may lead to life threatening complications and have a major impact on the quality of life of the patients. Therefore, biomarkers that would be instrumental in the choice of optimal type, combination and dose of drugs for an individual patient are urgently needed. The efficacy and toxicity of anticancer drugs in tumor cells is determined by the effective concentration in tumor cells, healthy tissues and by the presence and quantity of the drug targets. Enzymes active in drug metabolism and transport represent important determinants of the therapeutic outcome. The aim of this review was to summarize published data on associations of gene and protein expression, and genetic variability of putative biomarkers with response to therapy of colorectal cancer to 5-fluorouracil/leucovorin/oxaliplatin and 5 fluorouracil/leukovorin/irinotecan regimens. Gaps in the knowledge identified by this review may aid the design of future research and clinical trials. PMID- 25132750 TI - Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era of antibiotic resistance. AB - The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade, largely related to increasing clarithromycin resistance rates. From a microbiological standpoint, bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy. Nonetheless, several obstacles such as availability, complexity or tolerance prevent a general implementation of bismuth quadruple therapy, so non-bismuth quadruple regimens remain the best first-line treatment in clinical practice in many geographical areas. We review the rationale and efficacy of several optimization tools (increasing the length of duration, high dose acid suppression, probiotics), which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy. Then, we update available evidence on the effectiveness of several non-bismuth quadruple therapies (sequential, concomitant, hybrid, miscellaneous therapy), which have gained interest lately. We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and, finally we provide a novel regionalized therapeutic algorithm, based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens, upon local antibiotic resistance rates. PMID- 25132751 TI - Prevention of Helicobacter pylori infection in childhood. AB - Helicobacter pylori (H. pylori) infection is one of the most common infections worldwide. Although infection rates are falling in the developed and developing countries, H. pylori is still widespread in the world. This article has reviewed the important publications on H. pylori in childhood with a focus on its evolving transmission route and the source of infection and preventive strategies in childhood, PubMed was searched up to identify eligible studies. Relevant publications were searched using the following. PMID- 25132752 TI - Helicobacter pylori eradication in West Asia: a review. AB - The efficacy of first- and second-line Helicobacter pylori (H. pylori) eradication regimens varies considerably in West Asian countries, mainly due to the variable prevalence of resistant organisms. However, no review article has yet evaluated and compared the efficacy of different regimens among different countries of this region. Therefore, we conducted a review to select the best options and provide recommendations for H. pylori treatment in this geographic region. A search through PubMed was carried out to obtain relevant randomized clinical trials published in English language up to June 2013. According to the results, among different therapeutic regimens used as the first-line protocols, 10-d Bismuth-Furazolidone/Metronidazole quadruple therapy, 14-d Clarithromycin containing hybrid therapy and 14-d quadruple therapy including a proton pump inhibitor + Bismuth + Tetracycline (500 mg QID) + Metronidazole (500 mg TDS) seemed to be appropriate options. Among second-line therapeutic regimens, Bismuth based quadruple therapies containing Tetracycline and Furazolidone/Metronidazole, triple therapy containing Amoxicillin and Gatifloxacin and Quadruple therapy including Bismuth + Azithromycin and Ofloxacin seemed to be effective options. Third-line therapies were not evaluated in West Asia; most guidelines, however, recommend choosing optimal eradication regimen according to the pattern of antibiotic susceptibility of H. pylori. Although we limited our investigation to H. pylori eradication regimens in West Asia, the clinical significance of the results goes beyond the countries situated in this geographic region. In fact, the results are transferrable to any region as long as the patterns of resistance are the same. PMID- 25132753 TI - Medicinal plant activity on Helicobacter pylori related diseases. AB - More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-kappaB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori eradication and H. pylori induced related gastric disease prevention. PMID- 25132755 TI - Natural history of chronic hepatitis B: phases in a complex relationship. AB - Chronic hepatitis B (CHB) is a condition of global prevalence and its sequelae include cirrhosis and hepatocellular carcinoma. The natural history of CHB is a complex interplay of virological, environmental and host factors. The dynamic relationship between the virus and host evolves over the duration of the infection and different phases of the disease have been observed and described. These have been conceptualized in terms of the state of balance between the host immune system and the hepatitis B virus and have been given the labels immune tolerant, immune clearance, immune control and immune escape although other nomenclature is also used. Host factors, such as age at infection, determine progression to chronicity. Virological factors including hepatitis B viral load, mutations and genotype also have an impact on the adverse outcomes of the infection, as do hepatotoxic cofactors such as alcohol. Our understanding of the natural history of CHB has evolved significantly over the past few decades and characterizing the phase of disease of CHB remains an integral part of managing this virus in the clinic. PMID- 25132754 TI - Hepatitis B vaccine by intradermal route in non responder patients: an update. AB - Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary vaccination cycle are defined "no responders". Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Moreover there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type I diabetes mellitus, down's syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection. Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013. PMID- 25132757 TI - Proton pump inhibitor responsive esophageal eosinophilia, a distinct disease entity? AB - Recent studies have suggested the existence of a patient population with esophageal eosinophilia that responds to proton pump inhibitor therapy. These patients are being referred to as having proton pump inhibitor responsive esophageal eosinophilia (PPI-REE), which is currently classified as a distinct and separate disease entity from both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). The therapeutic effect of proton pump inhibitor (PPI) on PPI-REE is thought to act directly at the level of the esophageal mucosa with an anti-inflammatory capacity, and completely independent of gastric acid suppression. The purpose of this manuscript is to review the mechanistic data of the proposed immune modulation/anti-inflammatory role of the PPI at the esophageal mucosa, and the existence of PPI-REE as a distinct disease entity from GERD and EoE. PMID- 25132756 TI - Pancreatic cancer-improved care achievable. AB - Pancreatic adenocarcinoma is one of the most aggressive cancers, and the decline in mortality observed in most other cancer diseases, has so far not taken place in pancreatic cancer. Complete tumor resection is a requirement for potential cure, and the reorganization of care in the direction of high patient-volume centers, offering multimodal treatment, has improved survival and Quality of Life. Also the rates and severity grade of complications are improving in high volume pancreatic centers. One of the major problems worldwide is underutilization of surgery in resectable pancreatic cancer. Suboptimal investigation, follow up and oncological treatment outside specialized centers are additional key problems. New chemotherapeutic regimens like FOLFIRINOX have improved survival in patients with metastatic disease, and different adjuvant treatment options result in well documented survival benefit. Neoadjuvant treatment is highly relevant, but needs further evaluation. Also adjuvant immunotherapy, in the form of vaccination with synthetic K-Ras-peptides, has been shown to produce long term immunological memory in cytotoxic T-cells in long term survivors. Improvement in clinical outcome is already achievable and further progress is expected in the near future for patients treated with curative as well as palliative intention. PMID- 25132758 TI - Personalizing medicine for metastatic colorectal cancer: current developments. AB - Metastatic colorectal cancer (mCRC) is still one of the tumor types with the highest incidence and mortality. In 2012, colorectal cancer was the second most prevalence cancer among males (9%) and the third among females (8%). In this disease, early diagnosis is important to improve treatment outcomes. However, at the time of diagnosis, about one quarter of patients already have metastases, and overall survival of these patients at 5-years survival is very low. Because of these poor statistics, the development of new drugs against specific targets, including the pathway of angiogenesis, has witnessed a remarkable increase. So, targets therapies through epidermal growth factor and its receptor and also KRAS pathways modulation acquired a main role whether in association with standard chemotherapy and radiotherapy. With the current knowledge in the field of molecular biology, including genetic mutations and polymorphisms, we know better why patients respond so differently to the same treatments. So, in the future we can develop increasingly personalized treatments to the patient and not the disease. This review aims to summarize some molecular pathways and their relation to tumor growth, as well as novel targeted developing drugs and recently approved for mCRC. PMID- 25132759 TI - MiRNA as potential biomarkers and therapeutic targets for gastric cancer. AB - Gastric cancer is one of the leading causes of cancer mortality in the world. Aberrant expression of microRNAs (miRNAs) is the hallmark of this disease. MiRNAs are endogenous non-coding RNAs that are involved in many biological processes (e.g., cell proliferation, differentiation, apoptosis, invasion and development) through gene repression. Deregulation of miRNA expression in gastric tumors and cancer cell lines have been documented to contribute in tumorigenesis, and the expression signature may correlate with different cancer types and clinicopathological features. Here, we summarized the updated gastric cancer associated miRNAs and the downstream targets in the process of tumorigenesis. Recently, many researchers make use of the miRNA microarray platform to profile miRNA expression in gastric cancer and correlated with different clinical parameters. Its application on cancer diagnosis, prognosis and predicting treatment response rate are still underway and needs further investigation. Emerging roles of miRNAs with oncogenic or tumor suppressive properties in gastric tumorigenesis were discussed. Epigenetic silencing of miRNA by hypermethylation of promoter CpG island was also observed in gastric cancer. However, detailed mechanisms of how miRNAs regulate gene expression in gastric cancer has not been well studied. In this review, we highlight the up-to-date findings on the deregulated miRNAs in gastric cancer, and the potential use of miRNA in the clinical settings, such as diagnostic/prognostic markers and chemotherapeutic tools. PMID- 25132760 TI - Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer cells. AB - AIM: To investigate the effects of osteopontin (OPN) gene expression knockdown on colon cancer Lovo cells in vitro. METHODS: Four candidate small interfering RNA (siRNA) constructs targeting the OPN gene and a scrambled control sequence (NC siRNA) were synthesized and inserted into a pGPU6/GFP/Neo expression vector. After confirmation by restriction enzyme digestion and DNA sequencing, the recombinant plasmids were subsequently transfected into a human colon cancer cell line (Lovo) using a liposome transfection method. Stably transfected cells were maintained with G418 selection and referred to as Lovo-OPN-1, -2, -3, -4, and Lovo-NC cells. Knockdown efficiency of each of the four siRNA constructs was determined by real-time reverse transcription polymerase chain reaction assays and western blotting, and the construct with the most effective silencing was used for subsequent experiments. Cell proliferation, adhesion, and Matrigel invasion assays were performed to analyze the effects of OPN knockdown in stably transfected Lovo cells. The levels of four angiogenic factors, namely vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9 and urokinase plasminogen activator were detected by enzyme-linked immunosorbent assays (ELISA). RESULTS: Recombinant vectors containing OPN-specific and scrambled siRNA sequences were successfully constructed and stably transfected into Lovo cells. Compared with the control Lovo and Lovo-NC cells, the levels of OPN mRNA and protein expression in Lovo-OPN-1, -2, -3, and -4 were significantly reduced (all P < 0.05), with the most efficient reduction observed in Lovo-OPN-4 cells (P < 0.05). Relative to untransfected Lovo cells, OPN mRNA expression levels in Lovo-NC and Lovo-OPN-4 cells were 1.008 +/- 0.067 and 0.160 +/- 0.023, respectively. The relative OPN protein expression levels in Lovo, Lovo-NC, and Lovo-OPN-4 cells were 3.024 +/- 0.211, 2.974 +/- 0.630, and 0.121 +/- 0.008, respectively. Moreover, transfection with the scrambled sequence had no effect on the expression of OPN. After 24, 48, 72, and 96 h of cultivation, absorption values at 450 nm to assess proliferation of Lovo-OPN-4 cells were 0.210 +/- 0.017, 0.247 +/- 0.024, 0.314 +/- 0.037, and 0.359 +/- 0.043, respectively, which were significantly lower than those of Lovo (0.244 +/- 0.031, 0.313 +/- 0.024, 0.513 +/- 0.048 and 0.783 +/- 0.051) and Lovo-NC cells (0.241 +/- 0.029, 0.309 +/ 0.022, 0.563 +/- 0.023, and 0.735 +/- 0.067) (all P < 0.05). The absorption values at 595 nm, which were measured in a cell adhesion assay, showed that adhesion of Lovo-OPN-4 cells (0.215 +/- 0.036) was significantly decreased compared to Lovo (0.490 +/- 0.037) and Lovo-NC cells (0.462 +/- 0.043) (P < 0.05). The number of invasive Lovo-OPN-4 cells (16.1 +/- 1.9) was also significantly decreased compared to Lovo (49.9 +/- 5.4) and Lovo-NC cells (48.8 +/- 4.5) (P < 0.05). ELISA assays showed significant reductions in Lovo-OPN-4 cells compared to Lovo and Lovo-NC cells with regard to the expression of VEGF (1687.85 +/- 167.84 ng/L vs 2348.54 +/- 143.80 ng/L and 2284.39 +/- 138.62 ng/L, respectively), MMP-2 (2966.07 +/- 177.36 MUg/L vs 4084.74 +/- 349.54 MUg/L and 4011.41 +/- 424.48 MUg/L, respectively), MMP-9 (3782.89 +/- 300.64 MUg/L vs 5062.90 +/- 303.02 MUg/L and 4986.38 +/- 300.75 MUg/L, respectively) and uPA (1152.69 +/- 120.79 MUg/L vs 1380.90 +/- 147.25 MUg/L and 1449.80 +/- 189.92 MUg/L, respectively) (all P < 0.05). CONCLUSION: Knockdown of OPN gene expression suppresses colon cancer cell growth, adherence, invasion, and expression of angiogenic factors. PMID- 25132761 TI - Insulin resistance, adipokine profile and hepatic expression of SOCS-3 gene in chronic hepatitis C. AB - AIM: To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C genotype 1 with normal body weight, glucose and lipid profile. METHODS: The study group consisted of 31 patients with chronic hepatitis C and 9 healthy subjects. Total levels of adiponectin, leptin, resistin, visfatin, omentin, osteopontin and insulin were measured using an ELISA kit. The hepatic expression of SOCS-3 was determined by the use of the reverse transcription polymerase chain reaction method. RESULTS: Homeostasis model assessment for insulin resistance (HOMA-IR) values were significantly higher in hepatitis C virus (HCV) infected patients without metabolic disorders compared to healthy controls (2.24 vs 0.59, P = 0.0003). Hepatic steatosis was observed in 32.2% of patients with HCV infection and was found in patients with increased HOMA-IR index (2.81 vs 1.99, P = 0.05) and reduced adiponectin level (5.96 vs 8.37, P = 0.04). Inflammatory activity (G >= 2) was related to increased osteopontin concentration (34.04 vs 23.35, P = 0.03). Advanced liver fibrosis (S >= 2) was associated with increased levels of omentin and osteopontin (436.94 vs 360.09, P = 0.03 and 32.84 vs 20.29, P = 0.03) and reduced resistin concentration (1.40 vs 1.74, P = 0.047). No correlations were reported between adipokine profile, HOMA-IR values and hepatic expression of the SOCS-3 gene. CONCLUSION: We speculated that no relationship between adipokines and HOMA-IR values may indicate that HCV can induce insulin resistance itself. Some adipokines appear to be biochemical markers of steatosis, inflammation and fibrosis in patients with chronic HCV infection. (c) 2014 Baishideng Publishing Group Inc. All rights reserved. PMID- 25132762 TI - Caspase-1 inhibition alleviates acute renal injury in rats with severe acute pancreatitis. AB - AIM: To assess the effect of inhibition of caspase-1 on acute renal injury in rats with severe acute pancreatitis (SAP). METHODS: Forty-two Sprague-Dawley rats were randomly divided into three groups: healthy controls (HC, n = 6), SAP rats treated with saline (SAP-S, n = 18), or SAP rats treated with a caspase 1/interleukin (IL)-1beta-converting-enzyme (ICE) inhibitor (SAP-I-ICE, n = 18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile pancreatic duct. HC rats were subjected to identical treatment and surgical procedures without sodium taurocholate. Rats received an intraperitoneal injection of isotonic saline (SAP-S) or the inhibitor (SAP-ICE-I) at 2 and 12 h after induction of acute pancreatitis. Surviving rats were sacrificed at different time points after SAP induction; all samples were obtained and stored for subsequent analyses. The levels of blood urea nitrogen (BUN) and creatinine (Cr) were measured using automatic methods, and serum IL-1beta concentrations were measured by an enzyme-linked immunosorbent assay. Intrarenal expression of IL-1beta, IL-18 and caspase-1 mRNAs was detected by RT-PCR. IL-1beta protein expression and the pathologic changes in kidney tissues were observed by microscopy after immunohistochemical or hematoxylin and eosin staining, respectively. RESULTS: The serum levels of BUN and Cr in the SAP-S group were 12.48 +/- 2.30 mmol/L and 82.83 +/- 13.89 MUmol/L at 6 h, 23.53 +/- 2.58 mmol/L and 123.67 +/- 17.67 MUmol/L at 12 h, and 23.60 +/- 3.33 mmol/L and 125.33 +/- 21.09 MUmol/L at 18 h, respectively. All were significantly increased compared to HC rats (P < 0.01 for all). Levels in SAP-ICE-I rats were significantly decreased compared to SAP-S rats both at 12 and 18 h (P < 0.01 for all). Serum IL-1beta levels in the SAP-S group were 276.77 +/- 44.92 pg/mL at 6 h, 308.99 +/- 34.95 pg/mL at 12 h, and 311.60 +/- 46.51 pg/mL at 18 h; all significantly higher than those in the HC and SAP-ICE-I groups (P < 0.01 for all). Intrarenal expression of IL-1beta mRNA was weak in HC rats, but increased significantly in SAP-S rats (P < 0.01). ICE inhibition significantly decreased the expression of IL-1beta and IL 18 mRNAs (P < 0.05 for all vs SAP-S), whereas caspase-1 mRNA expression was not significantly different. Weak IL-1beta immunostaining was observed in HC animals, and marked staining was found in the SAP-S group mainly in renal tubular epithelial cells. IL-1beta immunostaining was significantly descended in SAP-ICE I rats compared to SAP-S rats (P < 0.05). Caspase-1 inhibition had no effect on the severity of kidney tissue destruction. CONCLUSION: The expression of caspase 1-activated cytokines IL-1beta and IL-18 plays a pivotal role in acute renal injury in rats with experimental SAP. Caspase-1 inhibition improves renal function effectively. PMID- 25132763 TI - Cost-effectiveness analysis of beta-blockers vs endoscopic surveillance in patients with cirrhosis and small varices. AB - AIM: To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices. METHODS: A stochastic analysis based on decision trees was performed to compare the cost-effectiveness of beta-blockers therapy starting from a diagnosis of small varices (Strategy 1) with that of endoscopic surveillance followed by beta blockers treatment when large varices are demonstrated (Strategy 2), for preventing variceal growth, bleeding and death in patients with cirrhosis and small esophageal varices. The basic nodes of the tree were gastrointestinal endoscopy, inpatient admission and treatment for bleeding, as required. All estimates were performed using a Monte Carlo microsimulation technique, consisting in simulating observations from known probability distributions depicted in the model. Eight-hundred-thousand simulations were performed to obtain the final estimates. All estimates were then subjected to Monte Carlo Probabilistic sensitivity analysis, to assess the impact of the variability of such estimates on the outcome distributions. RESULTS: The event rate (considered as progression of varices or bleeding or death) in Strategy 1 [24.09% (95%CI: 14.89%-33.29%)] was significantly lower than in Strategy 2 [60.00% (95%CI: 48.91% 71.08%)]. The mean cost (up to the first event) associated with Strategy 1 [823 L (95%CI: 106 L-2036 L)] was not significantly different from that of Strategy 2 [799 L (95%CI: 0 L-3498 L)]. The cost-effectiveness ratio with respect to this endpoint was equal to 50.26 L (95%CI: -504.37 L-604.89 L) per event avoided over the four-year follow-up. When bleeding episodes/deaths in subjects whose varices had grown were included, the mean cost associated with Strategy 1 was 1028 L (95%CI: 122 L-2581 L), while 1699 L (95%CI: 171 L-4674 L) in Strategy 2. CONCLUSION: Beta-blocker therapy turn out to be more effective and less expensive than endoscopic surveillance for primary prophylaxis of bleeding in patients with cirrhosis and small varices. PMID- 25132764 TI - Diagnostic accuracy of endoscopic ultrasonography for rectal neuroendocrine neoplasms. AB - AIM: To investigate the diagnostic accuracy of endoscopic ultrasonography (EUS) for rectal neuroendocrine neoplasms (NENs) and the differential diagnosis of rectal NENs from other subepithelial lesions (SELs). METHODS: The study group consisted of 36 consecutive patients with rectal NENs histopathologically diagnosed using biopsy and/or resected specimens. The control group consisted of 31 patients with homochronous rectal non-NEN SELs confirmed by pathology. Epithelial lesions such as cancer and adenoma were excluded from this study. One EUS expert blinded to the histological results reviewed the ultrasonic images. The size, original layer, echoic intensity and homogeneity of the lesions and the perifocal structures were investigated. The single EUS diagnosis recorded by the EUS expert was compared with the histological results. RESULTS: All NENs were located at the rectum 2-10 cm from the anus and appeared as nodular (n = 12), round (n = 19) or egg-shaped (n = 5) lesions with a hypoechoic (n = 7) or intermediate (n = 29) echo pattern and a distinct border. Tumors ranged in size from 2.3 to 13.7 mm, with an average size of 6.8 mm. Homogeneous echogenicity was seen in all tumors except three. Apart from three patients (stage T2 in two and stage T3 in one), the tumors were located in the second and/or third wall layer without involvement of the fourth and fifth layers. In the patients with stage T1 disease, the tumors were located in the second wall layer only in seven cases, the third wall layer only in two cases, and both the second and third wall layers in 27 cases. Approximately 94.4% (34/36) of rectal NENs were diagnosed correctly by EUS, and 74.2% (23/31) of other rectal SELs were classified correctly as non NENs. Eight cases of other SELs were misdiagnosed as NENs, including two cases of inflammatory lesions and one case each of gastrointestinal tumor, endometriosis, metastatic tumor, lymphoma, neurilemmoma, and hemangioma. The positive predictive value of EUS for rectal NENs was 80.9% (34/42), the negative predictive value was 92.0% (23/25), and the diagnostic accuracy was 85.1%. CONCLUSION: EUS has satisfactory diagnostic accuracy for rectal NENs with good sensitivity, but unfavorable specificity, making the differential diagnosis of NENs from other SELs challenging. PMID- 25132765 TI - Comparision of modified and conventional delta-shaped gastroduodenostomy in totally laparoscopic surgery. AB - AIM: To evaluate the safety and feasibility of a modified delta-shaped gastroduodenostomy (DSG) in totally laparoscopic distal gastrectomy (TLDG). METHODS: We performed a case-control study enrolling 63 patients with distal gastric cancer (GC) undergoing TLDG with a DSG from January 2013 to June 2013. Twenty-two patients underwent a conventional DSG (Con-Group), whereas the other 41 patients underwent a modified version of the DSG (Mod-Group). The modified procedure required only the instruments of the surgeon and assistant to complete the involution of the common stab incision and to completely resect the duodenal cutting edge, resulting in an anastomosis with an inverted T-shaped appearance. The clinicopathological characteristics, surgical outcomes, anastomosis time and complications of the two groups were retrospectively analyzed using a prospectively maintained comprehensive database. RESULTS: DSG procedures were successfully completed in all of the patients with histologically complete (R0) resections, and none of these patients required conversion to open surgery. The clinicopathological characteristics of the two groups were similar. There were no significant differences between the groups in the operative time, intraoperative blood loss, extension of the lymph node (LN) dissection and number of dissected LNs (150.8 +/- 21.6 min vs 143.4 +/- 23.4 min, P = 0.225 for the operative time; 26.8 +/- 11.3 min vs 30.6 +/- 14.8 mL, P = 0.157 for the intraoperative blood loss; 4/18 vs 3/38, P = 0.375 for the extension of the LN dissection; and 43.9 +/ 13.4 vs 39.5 +/- 11.5 per case, P = 0.151 for the number of dissected LNs). The anastomosis time, however, was significantly shorter in the Mod-Group than in the Con-Group (13.9 +/- 2.8 min vs 23.9 +/- 5.6 min, P = 0.000). The postoperative outcomes, including the times to out-of-bed activities, first flatus, resumption of soft diet and postoperative hospital stay, as well as the anastomosis size, did not differ significantly (1.9 +/- 0.6 d vs 2.3 +/- 1.5 d, P = 0.228 for the time to out-of-bed activities; 3.2 +/- 0.9 d vs 3.5 +/- 1.3 d, P = 0.295 for the first flatus time; 7.5 +/- 0.8 d vs 8.1 +/- 4.3 d, P = 0.489 for the resumption of a soft diet time; 14.3 +/- 10.6 d vs 11.5 +/- 4.9 d, P = 0.148 for the postoperative hospital stay; and 30.5 +/- 3.6 mm vs 30.1 +/- 4.0 mm, P = 0.730 for the anastomosis size). One patient with minor anastomotic leakage in the Con Group was managed conservatively; no other patients experienced any complications around the anastomosis. The operative complication rates were similar in the Con- and Mod-Groups (9.1% vs 7.3%, P = 1.000). CONCLUSION: The modified DSG, an alternative reconstruction in TLDG for GC, is technically safe and feasible, with a simpler process that reduces the anastomosis time. PMID- 25132766 TI - Clinical epidemiology of gastric cancer in Hehuang valley of China: a 10-year epidemiological study of gastric cancer. AB - AIM: To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley, China, to provide a reference for treatment and prevention of regional gastric cancer. METHODS: Between February 2003 and February 2013, the records of 2419 patients with gastric cancer were included in this study. The patient's characteristics, histological and pathological features, as well as the dietary habits of the patients, were investigated. RESULTS: The clinical data showed that adenocarcinoma was the leading histological type of gastric cancer in this area. Characteristics of gastric cancer in different ethnic groups and age showed that the 60.55-65.50 years group showed the high incidence of gastric cancer in all ethnic groups. There were more male gastric cancer patients than female. Intestinal was the most common type of gastric cancer in the Hehuang valley. There was no significant difference in the proportion of sex in terms of Helicobacter pylori infection. The impact of dietary habits on gastric cancer showed that regular consumption of fried or grilled food, consumption of high-salt, high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females. CONCLUSION: Differences existed in race, sex, and age of patients according to the epidemiology of gastric cancer in the Hehuang valley. Moreover, dietary habits was also an important factor contributing to gastric cancer. PMID- 25132767 TI - Comparative analysis of ERCP, IDUS, EUS and CT in predicting malignant bile duct strictures. AB - AIM: To compare endoscopic retrograde cholangio-pancreatography (ERCP), intraductal ultrasound (IDUS), endosonography (EUS), endoscopic transpapillary forceps biopsies (ETP) and computed tomography (CT) with respect to diagnosing malignant bile duct strictures. METHODS: A patient cohort with bile duct strictures of unknown etiology was examined by ERCP and IDUS, ETP, EUS, and CT. The sensitivity, specificity, and accuracy rates of the diagnostic procedures were calculated based on the definite diagnoses proved by histopathology or long term follow-up in those patients who did not undergo surgery. For each of the diagnostic measures, the sensitivity, specificity, and accuracy rates were calculated. In all cases, the gold standard was the histopathologic staging of specimens or long-term follow-up of at least 12 mo. A comparison of the accuracy rates between the localization of strictures was performed by using the Mann Whitney U-test and the chi(2) test as appropriate. A comparison of the accuracy rates between the diagnostic procedures was performed by using the McNemar's test. Differences were considered statistically significant if P < 0.05. RESULTS: A total of 234 patients (127 males, 107 females, median age 64, range 20-90 years) with indeterminate bile duct strictures were included. A total of 161 patients underwent operative exploration; thus, a surgical histopathological correlation was available for those patients. A total of 113 patients had malignant disease proven by surgery; in 48 patients, benign disease was surgically found. In these patients, the decision for surgical exploration was made due to the suspicion of malignant disease in multimodal diagnostics (ERCP, CT, or EUS). Fifty patients had a benign diagnosis and were followed by a surveillance protocol with a follow-up of at least 12 mo; the median follow-up was 34 mo. Twenty-three patients had extended malignant disease, and thus were considered palliative. A comparison of the different diagnostic tools for detecting bile duct malignancy resulted in accuracy rates of 91% (ERCP/IDUS), 59% (ETP), 92% (IDUS + ETP), 74% (EUS), and 73% (CT), respectively. In the subgroup analysis, the accuracy rates (%, ERCP + IDUS/ETP/IDUS + ETP; EUS; CT) for each tumor entity were as follows: cholangiocellular carcinoma: 92%/74%/92%/70%/79%; pancreatic carcinoma: 90%/68%/90%/81%/76%; and ampullary carcinoma: 88%/90%/90%/76%/76%. The detection rate of malignancy by ERCP/IDUS was superior to ETP (91% vs 59%, P < 0.0001), EUS (91% vs 74%, P < 0.0001) and CT (91% vs 73%, P < 0.0001); EUS was comparable to CT (74% vs 73%, P = 0.649). When analyzing accuracy rates with regard to localization of the bile duct stenosis, the accuracy rate of EUS for proximal vs distal stenosis was significantly higher for distal stenosis (79% vs 57%, P < 0.0001). CONCLUSION: ERCP/IDUS is superior to EUS and CT in providing accurate diagnoses of bile duct strictures of uncertain etiology. Multimodal diagnostics is recommended. PMID- 25132768 TI - One fifth of hospitalizations for peptic ulcer-related bleeding are potentially preventable. AB - AIM: To calculate the proportion of potentially preventable hospitalizations due to peptic ulcer disease (PUD), erosive gastritis (EG) or duodenitis (ED). METHODS: Retrospective cohort study using ICD-10 codes to identify all patients with upper gastrointestinal hemorrhage secondary to endoscopically proven PUD, EG or ED during the period from March 2007 to October 2010 in three major metropolitan hospitals in Melbourne, Australia. Patients were divided into "high risk" (those who would benefit from gastroprotection) and "not high risk" groups as defined by established guidelines. Mean Rockall score, transfusion requirement, length of stay, rebleeding rates, need for surgery and in-hospital mortality was compared between "high risk" and "not high risk" groups. Within the "high risk" group, those on gastroprotection and those with no gastroprotection were also compared. RESULTS: Five hundred and seven patients were included for analysis of which 174 were classified as high risk. Median values of complete Rockall Score (5 vs 4, P = 0.002) and length of stay (5 d vs 4 d, P = 0.04) were higher in the high risk group but in-hospital mortality was lower (0.6% vs 3.9%, P = 0.03). 130 out of the 174 patients in the high risk group were not taking recommended gastroprotective therapy prior to hospitalization. Past history of PUD (OR = 3.7, P = 0.006) and clopidogrel use (OR = 3.2, P = 0.007) significantly predicted prescription of gastroprotective therapy. Using proton pump inhibitor protection rates of 50%-85% from published studies, an estimation of 13% to 22% of the total number of the hospitalizations due to PUD or EG/ED related bleeding may have been preventable. CONCLUSION: Up to one fifth of all hospitalizations for bleeding secondary to PUD or EG/ED are potentially preventable. PMID- 25132769 TI - Phenol-based endoscopic ultrasound-guided celiac plexus neurolysis for East Asian alcohol-intolerant upper gastrointestinal cancer patients: a pilot study. AB - AIM: To investigate the effectiveness of phenol for the relief of cancer pain by endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN). METHODS: Twenty two patients referred to our hospital with cancer pain from August 2009 to July 2011 for EUS-CPN were enrolled in this study. Phenol was used for 6 patients with alcohol intolerance and ethanol was used for 16 patients without alcohol intolerance. The primary endpoint was the positive response rate (pain score decreased to <= 3) on postoperative day 7. Secondary endpoints included the time to onset of pain relief, duration of pain relief, and complication rates. RESULTS: There was no significant difference in the positive response rate on day 7. The rates were 83% and 69% in the phenol and ethanol groups, respectively. Regarding the time to onset of pain relief, in the phenol group, the median pre treatment pain score was 5, whereas the post-treatment scores decreased to 1.5, 1.5, and 1.5 at 2, 8, and 24 h, respectively (P < 0.05). In the ethanol group, the median pre-treatment pain score was 5.5, whereas the post-treatment scores significantly decreased to 2.5, 2.5, and 2.5 at 2, 8, and 24 h, respectively (P < 0.01). There was no significant difference in the duration of pain relief between the phenol and ethanol groups. No significant difference was found in the rate of complications between the 2 groups; however, burning pain and inebriation occurred only in the ethanol group. CONCLUSION: Phenol had similar pain-relieving effects to ethanol in EUS-CPN. Comparing the incidences of inebriation and burning pain, phenol may be superior to ethanol in EUS-CPN procedures. PMID- 25132770 TI - Length of negative resection margin does not affect local recurrence and survival in the patients with gastric cancer. AB - AIM: To investigate the influence of the resection margin on local recurrence and survival in gastric cancer patients. METHODS: We reviewed the medical records of 1788 patients who had undergone gastrectomy for gastric cancer at the Seoul National University Bundang Hospital, South Korea, between May 2003 and July 2009. The patients were divided into early and advanced gastric cancer groups. In each group, we analyzed the relationship between clinicopathologic factors and survival outcomes, and compared the hazard rates of event occurrence between patients with resection margins above and below the cut-off value, using a Cox proportional hazard model. RESULTS: The early and advanced gastric cancer groups included 1001 and 787 patients, respectively. The hazard rates of event occurrence did not significantly differ between the patients with resection margins above the cut-off value and those with resection margins below the cut off value (P > 0.05, in all comparisons). Based on the multivariable analyses, the proximal and distal resection margins were not significantly associated with survival outcomes and local recurrence (P > 0.05, in all analyses). CONCLUSION: The proximal or distal resection margins did not affect the prognosis of patients with gastric cancer if the margins were pathologically negative. PMID- 25132771 TI - Refeeding syndrome in Southeastern Taiwan: our experience with 11 cases. AB - AIM: To present our experience with refeeding syndrome in southeastern Taiwan. METHODS: We conducted a retrospective study during a 2-year period at the Mackay Memorial Hospital, Taitung Branch. We enrolled patients with very little or no nutrition intake for more than 10 d, a high risk group of refeeding syndrome, including those suffering from alcohol abuse, cancerous cachexia, chronic malnutrition, and prolonged starvation. RESULTS: A total of 11 patients (7 males, 4 females) with nasogastric feeding were included as having refeeding syndrome. Most of them had the symptoms of diarrhea, lethargy, and leg edema. The initial nutritional supplement was found to be relatively high in calories (1355.1 +/- 296.2 kcal/d), high in protein (47.3 +/- 10.4 gm/d), low in vitamin B1 (2.0 +/- 0.5 mg/d), low in potassium (1260.4 +/- 297.7 mg/d), and low in phosphorus (660.1 +/- 151.8 mg/d). Furthermore, hypophosphatemia (2.4 +/- 0.9 mg/dL) was noted during follow-up. Based on the suggestions of a dietician and a gastroenterologist, the clinical disorders of diarrhea, malaise and leg edema were significantly improved. The level of phosphate was also increased (3.3 +/- 0.6 mg/dL). CONCLUSION: Refeeding syndrome is an overlooked and risky disorder that has some potentially fatal complications. Nasogastric feeding in nursing homes is an important risk factor for patients and deserves greater attention based on the initial results of this study. PMID- 25132772 TI - Techniques and feasibility of laparoscopic extended right hemicolectomy with D3 lymphadenectomy. AB - AIM: To illustrate the critical techniques and feasibility of laparoscopic extended right hemicolectomy (LERH), according to our previous experience. METHODS: Anatomical relationship and operative techniques were demonstrated. One hundred and five consecutive patients who underwent extended right hemicolectomy with D3 lymphadenectomy between January 2008 and May 2011 were included in the present study [laparoscopic group (n = 48) vs open group (n = 57)]. RESULTS: The right retrocolic space was the main surgical plan of the LERH. The superior mesenteric vein was the most important anatomical landmark for vascular dissection. The medial-to-lateral dissection approach made the LERH performed efficiently. Compared with the open group, the LERH group had less blood loss (111.7 +/- 127.8 mL vs 170.2 +/- 49.7 mL, P = 0.023), faster return of flatus (3.0 +/- 1.6 d vs 3.7 +/- 1.3 d, P = 0.019), and earlier diet (4.2 +/- 1.4 d vs 5.0 +/- 1.2 d, P = 0.005). Five patients (10.4%) underwent conversion during laparoscopic surgery. The cancer recurrence rates between the two groups were comparable (laparoscopic vs open, 8.6% vs 9.1%, P = 0.335). CONCLUSION: For an advanced tumor located at the hepatic flexure or proximal transverse colon, LERH with D3 lymphadenectomy using a medial-to-lateral approach seems to be safe and feasible when the superior mesenteric vein serves as the main anatomical landmark and the right retrocolic space severed as the surgical plan. PMID- 25132773 TI - Prognostic nutritional index predicts postoperative complications and long-term outcomes of gastric cancer. AB - AIM: To investigate the impact of prognostic nutritional index (PNI) on the postoperative complications and long-term outcomes in gastric cancer patients undergoing total gastrectomy. METHODS: The data for 386 patients with gastric cancer were extracted and analyzed between January 2003 and December 2008 in our center. The patients were divided into two groups according to the cutoff value of the PNI: those with a PNI >= 46 and those with a PNI < 46. Clinicopathological features were compared between the two groups and potential prognostic factors were analyzed. The relationship between postoperative complications and PNI was analyzed by logistic regression. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. RESULTS: The optimal cutoff value of the PNI was set at 46, and patients with a PNI >= 46 and those with a PNI < 46 were classified into PNI-high and PNI-low groups, respectively. Patients in the PNI-low group were more likely to have advanced tumor (T), node (N), and TNM stages than patients in the PNI-high group. The low PNI is an independent risk factor for the incidence of postoperative complications (OR = 2.223). The 5-year overall survival (OS) rates were 54.1% and 21.1% for patients with a PNI >= 46 and those with a PNI < 46, respectively. The OS rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stages II (P = 0.001) and III (P < 0.001) disease. CONCLUSION: The PNI is a simple and useful marker not only to identify patients at increased risk for postoperative complications, but also to predict long-term survival after total gastrectomy. The PNI should be included in the routine assessment of advanced gastric cancer patients. PMID- 25132774 TI - Risk factors associated with early and late HAT after adult liver transplantation. AB - AIM: To identify risk factors that might contribute to hepatic artery thrombosis (HAT) after liver transplantation (LT). METHODS: The perioperative and follow-up data of a total of 744 liver transplants, performed from February 1999 to July 2010, were retrospectively reviewed. HAT developed in 20 patients (2.7%). HAT was classified as early (occurring in fewer than 30 d post LT) or late (occurring more than 30 d post LT). Early HAT developed in 14 patients (1.9%). Late HAT developed in 6 patients (0.8%). Risk factors associated with HAT were analysed using the chi(2) test for univariate analysis and logistic regression for multivariate analysis. RESULTS: Lack of ABO compatibility, recipient/donor weight ratio >= 1.15, complex arterial reconstruction, duration time of hepatic artery anastomosis > 80 min, duration time of operation > 10 h, dual grafts, number of units of blood received intraoperatively >= 7, number of units of fresh frozen plasma (FFP) received intraoperatively >= 6, postoperative blood transfusion and postoperative FFP use were significantly associated with early HAT in the univariate analysis (P < 0.1). After logistic regression, independent risk factors associated with early HAT were recipient/donor weight ratio >= 1.15 (OR = 4.499), duration of hepatic artery anastomosis > 80 min (OR = 5.429), number of units of blood received intraoperatively >= 7 (OR = 4.059) and postoperative blood transfusion (OR = 6.898). Graft type (whole/living-donor/split), duration of operation > 10 h, retransplantation, rejection reaction, recipients with diabetes preoperatively and recipients with a high level of blood glucose or diabetes postoperatively were significantly associated with late HAT in the univariate analysis (P < 0.1). After logistic regression, the independent risk factors associated with early HAT were duration of operation > 10 h (OR = 6.394), retransplantation (OR = 21.793) and rejection reactions (OR = 16.936). CONCLUSION: Early detection of these risk factors, strict surveillance protocols by Doppler ultrasound and prophylactic anticoagulation for recipients at risk might be determined prospectively. PMID- 25132776 TI - Chronic permanent hypoxemia predisposes to mild elevation of liver stiffness. AB - AIM: To evaluate the impact of long term permanent hypoxemia noticed in patients with non operated congenital cyanogenic cyanotic cardiopathy on liver stiffness. METHODS: We included ten adult patients with non operated inoperate cyanotic cardiopathy and ten matched patients for age and gender admitted to the gastroenterology department for proctologic diseases; Clinical and laboratory data were collected [age, gender, body mass index, oxygen saturation, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), glycemia and cholesterol]. Measurement of hepatic stiffness by transient elastography was carried out in all patients using the Fibroscan device. All patients underwent an echocardiography to eliminate congestive heart failure. RESULTS: Among the patients with cyanotic cardiopathy, median liver stiffness 5.9 +/- 1.3 kPa was greater than control group (4.7 +/- 0.4 kPa) (P = 0.008). Median levels of GOT, GPT, gamma-glutamyltransferase, glycemia and cholesterol were comparable in cardiopathy and control group. In regression analysis including age, gender, body mass index, oxygen saturation, GOT, GPT, glycemia, cholesterol showed that only oxygen saturation was related to liver stiffness (r = -0.63 P = 0.002). CONCLUSION: Chronic permanent hypoxemia can induce mild increase of liver stiffness, but further studies are needed to explore the histological aspects of liver injury induced by chronic permanent hypoxemia. PMID- 25132775 TI - Human liver stem/progenitor cells decrease serum bilirubin in hyperbilirubinemic Gunn rat. AB - AIM: To test the ability of adult-derived human liver stem/progenitor cells (ADHLSC) from large scale cultures to conjugate bilirubin in vitro and in bilirubin conjugation deficient rat. METHODS: ADHLSC from large scale cultures were tested for their phenotype and for their capacity to conjugate bilirubin in vitro after hepatogenic differentiation. In vivo, Gunn rats [uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) deficient animal] were injected with ADHLSC and cryopreserved hepatocytes (positive control). Two, 4, 13 and 27 wk post transplantation, transplanted Gunn rat bilirubin serum levels were determined by high performance liquid chromatography. Human transplanted cell engraftment was assessed 27 wk post-transplantation using immunohistochemistry and RTqPCR. RESULTS: Large scale culture conditions do not modify ADHLSC phenotype, ADHLSC were able to specifically conjugate bilirubin. ADHLSC were intraportally injected into Gunn rats and blood UCB was measured at different times post transplantation, infused-Gunn rats exhibited a metabolic effect 3 mo post transplantation and maintained over a 6 mo period. ADHLSC engraftment into Gunn rat's liver was demonstrated by RTqPCR and immunohistochemistry against albumin and UGT1A1. CONCLUSION: ADHLSC from large scale cultures are efficient in conjugating bilirubin in vitro and in restoring a deficient metabolic function (reducing bilirubin level) in hyperbilirubinemic rats. PMID- 25132777 TI - Preoperative colonoscopy through the colonic stent in patients with colorectal cancer obstruction. AB - AIM: To evaluate the feasibility of a preoperative colonoscopy through a self expendable metallic stent (SEMS) and to identify the factors that affect complete colonoscopy. METHODS: A total of 48 patients who had SEMS placement because of acute malignant colonic obstruction underwent preoperative colonoscopy. After effective SEMS placement, patients who showed complete resolution of radiological findings and clinical signs of acute colon obstruction underwent a standard bowel preparation. Preoperative colonoscopy was then performed using a standard colonoscope. If the passage of colonoscope was not feasible gastroscope was used. After colonoscopy, cecal intubation time, grade of bowel preparation, tumor location, stent location, presence of synchronous polyps or cancer, damage to colonoscopy and bleeding, and stent migration after colonoscopy were recorded. RESULTS: Complete evaluation with colonoscope was possible in 30 patients (62.5%). In this group, adenoma was detected in 13 patients (43.3%). The factors that affected complete colonoscopy were also analyzed: Tumor location at an angle; stent placement at an angle; and stent expansion diameter, which affected complete colonoscopy significantly. However in multivariate analysis, stent expansion diameter was the only significant factor that affected complete colonoscopy. Complete evaluation using additional gastroscope was feasible in 42 patients (87.5%). CONCLUSION: Preoperative colonoscopy through the colonic stent using only conventional colonoscope was unfavorable. The narrow expansion diameter of the stent may predict unfavorable outcome. In such a case, using small caliber scope should be considered and may expect successful outcome. PMID- 25132778 TI - Aerobic exercise improves gastrointestinal motility in psychiatric inpatients. AB - AIM: To evaluate the benefit of aerobic exercise on colonic transit time (CTT) for psychiatric inpatients in a closed ward. METHODS: Sixty consecutive adult inpatients of the Somang Hospital Psychiatry Unit (Eumsung-gun, South Korea), without CTT-related diseases or drug therapies, were recruited for study from March to June of 2012. Upon enrollment, the patients were randomly assigned to partake in a 12-wk instructor-led group aerobic exercise program (exercise group; n = 30) or to maintain their ordinary daily activities (control group; n = 30). The exercise program was structured as 10 min warm-up (stretching), 40 min exercise, and 10 min cool-down (stretching) for three days each week. The exercise sessions consisted of walking only in week one and aerobics from weeks two to 12, with increasing intensity (50% heart rate reserve (HRR) for weeks one to four, 60% HRR for weeks five to eight, and 70% HRR for weeks nine to 12). CTT was measured before (baseline) and after (week 12) the exercise program, in duplicate (on days four and seven), using abdominal radiography and the multiple radio-opaque marker technique. Changes in the exercising patients' CTT and weight , cardiovascular- and fitness-related parameters were statistically assessed. RESULTS: The study dropout rate was 30.0%, with 23 patients in the exercise group and 19 patients in the control group completing the study. At week 12, the exercise group showed decreases in body weight (mean +/- SE) baseline: 69.4 +/- 2.8 vs study-end: 67.6 +/- 2.7; P < 0.635) and body mass index (BMI) (25.2 +/- 1.1 vs 24.9 +/- 0.8; P < 0.810), but the extent of change was not significantly different from that experienced by the control group (body weight: 68.8 +/- 4.0 vs 68.8 +/- 3.9; BMI: 24.3 +/- 1.1 vs 24.4 +/- 1.2). However, the exercise group showed significant improvements in leg muscle strength (baseline: 41.7 +/- 4.3 vs study-end: 64.1 +/- 5.0; P < 0.001), cardio-respiratory endurance (120.5 +/- 4.5 vs 105.4 +/- 2.8; P < 0.004), and leg muscle elasticity and power output (21.5 +/ 2.6 vs 30.6 +/- 2.8; P < 0.001). The exercise group showed an exercise-induced reduction in total CTT (baseline: 54.2 +/- 8.0 vs 30.3 +/- 6.1), which was significantly different from that experienced by the control group over the 12-wk period (48.6 +/- 9.3 vs 48.3 +/- 12.3; P = 0.027); however, the exercise-induced decreases in CTT involving the three colonic segments examined (right, left and recto-sigmoid) showed no significant differences from the control group. CONCLUSION: A 12-wk aerobic exercise program can benefit psychiatric inpatients by increasing intestinal motility, possibly decreasing risk of metabolic- and cardiovascular-related disease. PMID- 25132779 TI - Diagnostic value of controlled attenuation parameter for liver steatosis in patients with chronic hepatitis B. AB - AIM: To study the diagnostic value of controlled attenuation parameter (CAP), evaluated by transient elastography, for liver steatosis in patients with chronic hepatitis B (CHB). METHODS: Eighty-eight patients with CHB were enrolled in this study. All of the patients were subjected to transient elastography to determine CAP. These patients also underwent liver biopsy in the same period. Using liver biopsy as a reference, we determined receiver operating characteristic (ROC) curves for different endpoints. Areas under the ROC curves (AUCs) were used to evaluate the diagnostic importance of CAP for liver steatosis in patients with CHB. RESULTS: A positive correlation was observed between the AUCs of CAP and liver pathological stage (r = 0.582, P < 0.05). CAP was not correlated with inflammation degree and fibrosis degree (r = -0.025, P > 0.05; r = 0. 068, P > 0.05). The mean CAP value at S0 was 209.59 +/- 41.25 dB/m, 223.84 +/- 35.28 dB/m at S1, 274.17 +/- 43.69 dB/m at S2, and 312.50 +/- 25.44 dB/m at S3. CAP values among S0, S1, S2, and S3 were significantly different (F = 17.79, P < 0.01). The AUC values for CAP were 0.711 (0.592-0.870), 0.868 (0.748-0.989), and 0.974 (0.922-1.026) for S1, S2, and S3, respectively. The optimal cut-off values were 219.5, 230.0, and 283.5 dB/m. CONCLUSION: CAP is a novel tool that can be used to assess the degree of steatosis. PMID- 25132780 TI - Relationship between methylation and colonic inflammation in inflammatory bowel disease. AB - AIM: To investigate the relationship between the methylation status in the SLIT2 and TGFB2 promoters and colonic inflammation in inflammatory bowel disease patients. METHODS: We evaluated the methylation status of 2 genes (SLIT2 and TGFB2) in 226 biopsies taken from 62 colonoscopies of 38 patients (29 ulcerative colitis and 9 Crohn's colitis) using methylation-specific melting curve analysis. The relationships between methylation status and clinical, biological, endoscopic and histological activities were evaluated. Twenty-three of the 38 patients had a second colonoscopy and were included in a longitudinal analysis. Numerical results were given as the means +/- SD of the sample and range, except when specified. Student t analysis, U Mann Whitney and ANOVA factor were used to compare the means. Qualitative results were based on the chi(2) test. RESULTS: SLIT2 methylation was more frequent in samples with endoscopic activity than with endoscopic remission (55% vs 18%, P < 0.001). SLIT2 methylation was also higher in samples with acute inflammation (56.5%) than in samples with chronic (24%) or absent inflammation (15%) (P < 0.001). For TGFB2 methylation, the correlation was only significant with endoscopic activity. Methylation was higher in the distal colon for both genes (P < 0.001 for SLIT2 and P = 0.022 for TGFB2). In the multivariate analysis, only inflammation status (and not disease duration or extension) was independently associated with SLIT2 methylation [OR = 6.6 (95%CI: 1.65-27.36), P = 0.009]. In the longitudinal analysis, the maintenance of endoscopic remission was protective for methylation. CONCLUSION: Endoscopic and histological inflammation are predictive for SLIT2 methylation. PMID- 25132781 TI - Early viral kinetics during hepatitis C virus genotype 6 treatment according to IL28B polymorphisms. AB - AIM: To investigate the early viral kinetics and interleukin-28B (IL28B) polymorphisms of hepatitis C genotype 6 during pegylated interferon and ribavirin therapy. METHODS: Sixty-five patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon and ribavirin (PEG-IFN/RBV) were included, of whom 15 (23.1%), 16 (24.6%) and 34 (52.3%) patients were infected with hepatitis C genotype 1 (HCV-1), genotype 3 (HCV-3) and genotype 6 (HCV-6), respectively. Serum HCV-RNA levels were measured frequently during the first 4-wk of therapy. DNA extracted from samples was analyzed for the IL28B single nucleotide polymorphism (SNP) rs12979860 by polymerase chain reaction and direct sequencing. RESULTS: During the first 4-wk of therapy, the mean viral decline for patients with HCV-6 (5.55 +/- 1.82 log10IU/mL) was comparable to that of patients with HCV-3 (5.55 +/- 1.82 log10IU/mL vs 5.86 +/- 1.02 log10IU/mL, P = 0.44) and was significantly higher than patients with HCV-1 (5.55 +/- 1.82 log10IU/mL vs 4.23 +/- 1.99 log10IU/mL, P = 0.04). In the HCV-6 group, the first phase (days 0 2) viral decline was significantly higher in patients with the favorable rs12979860 CC than non-CC genotypes (2.46 +/- 1.01 log10IU/mL/wk vs 1.70 +/- 0.67 log10IU/mL, respectively, P = 0.045). A statistically insignificant decrease in the second-phase (days 7-28) decline was also found in patients with the CC genotype than those with the non-CC genotype, though not significantly different (1.24 +/- 0.64 log10IU/mL/wk vs 0.80 +/- 0.65 log10IU/mL/wk, respectively, P = 0.172). At baseline, the SNP genotype was an independent predictor of rapid virological response but not of sustained virological response. CONCLUSION: The IL28B genotype was linked to an impact on early viral kinetics in response to PEG IFN/RBV therapy in HCV-6 infected patients. PMID- 25132782 TI - Coagulopathy in a subtype of choledochal cyst and management strategy. AB - AIM: To evaluated our management algorithm of the coagulopathy. We evaluated our management algorithm of the coagulopathy. METHODS: Between October 2001 and January 2013, 160 CDC children with coagulopathy (fibrinogen, FIB < 2 g/L) were recruited. FIB >= 1 g/L is generally required for safe elective surgery. We used FIB level as an indicator when: (1) patients with FIB levels between 1-2 g/L underwent one-stage definitive operation; and (2) patients with FIB < 1 g/L underwent 3 d of medical treatment. Thereafter, those with FIB >= 1 g/L underwent one-stage definitive operation whereas those with FIB < 1 g/L underwent external biliary drainage to allow liver function improvement. Those patients with liver function improvements underwent definitive operation after 7 d of drainage. RESULTS: After preoperative optimization, 92.5% of CDC children with coagulopathy underwent successful one-stage definitive operation. The remaining 7.5% of CDC children required initial external bile drainage, and underwent definitive operation 11 d after the admission. The mean operative time and postoperative recovery duration were comparable to those with normal coagulations. The median follow-up period was 57 mo. No blood transfusion or other postoperative complications were encountered. CONCLUSION: Following our management protocol, the majority of CDC children with coagulopathy can be managed with one-stage definitive operation. PMID- 25132783 TI - Predictors for failure of stent treatment for benign esophageal perforations - a single center 10-year experience. AB - AIM: To investigate possible predictors for failed self-expandable metallic stent (SEMS) therapy in consecutive patients with benign esophageal perforation-rupture (EPR). METHODS: All patients between 2003-2013 treated for EPR at the Karolinska University Hospital, a tertiary referral center, were studied with regard to initial management with SEMS. Patients with malignancy as an underlying cause and those with anastomotic leakages were excluded. Sealing of the perforation with a covered SEMS was the primary strategy whenever feasible. Stent therapy failure was defined as a radical change of treatment strategy due to uncontrolled mediastinitis, which in this setting consisted of emergency esophagectomy with end-esophagostomy or death as a consequence of the perforation and subsequent uncontrolled sepsis. Patient and lesion characteristics were analyzed and are presented as median and interquartile range. Possible predictors for failed stent therapy were analyzed with uni-variate logistic regression, while variables with P < 0.2 were further analyzed with multi-variate logistic regression. RESULTS: Of the total number of 48 patients presenting with EPR, 40 patients (83.3%) were treated with SEMS at the time of admission, with an intention to heal the perforation. Twenty-three patients had Boerhaave's syndrome (58%), 16 had an iatrogenic perforation (40%) and 1 had external trauma to the esophagus (3%). The total in-hospital mortality, including the cases that had other initial treatments (n = 8), was 10.4% and 7.5% among those who were subjected to the SEMS based strategy. In 33 of the 40 patients (82.5%) who were treated with stent, the EPR healed without further change in treatment strategy. Patients classified as treatment success received a SEMS at a median time of 1 (1-1) d after the actual EPR, compared to 3 (1-10) d among those where the initial treatment failed, P = 0.039 in uni-variate analysis and P = 0.052 in multi-variate analysis. No other significant factors emerged, indicating an increased risk for failure. Six of 7 patients, where stent treatment of the defect failed, underwent an emergency esophagectomy with end esophagostomy and one patient died. CONCLUSION: SEMS as an upfront therapeutic strategy seems to be a successful concept, when applied to an unselected group of patients with EPR. PMID- 25132784 TI - Efficacy of morning-only 4 liter sulfa free polyethylene glycol vs 2 liter polyethylene glycol with ascorbic acid for afternoon colonoscopy. AB - AIM: To compare the bowel cleansing efficacy of same day ingestion of 4-L sulfa free polyethylene glycol (4-L SF-PEG) vs 2-L polyethylene glycol solution with ascorbic acid (2-L PEG + Asc) in patients undergoing afternoon colonoscopy. METHODS: 206 patients (mean age 56.7 years, 61% male) undergoing outpatient screening or surveillance colonoscopies were prospectively randomized to receive either 4-L SF-PEG (n = 104) or 2-L PEG + Asc solution (n = 102). Colonoscopies were performed by two blinded endoscopists. Bowel preparation was graded using the Ottawa scale. Each participant completed a satisfaction and side effect survey. RESULTS: There was no difference in patient demographics amongst groups. 4-L SF-PEG resulted in better Ottawa scores compared to 2-L PEG + Asc, 4.2 vs 4.9 (P = 0.0186); left colon: 1.33 vs 1.57 respectively (P = 0.0224), right colon: 1.38 vs 1.63 respectively (P = 0.0097). No difference in Ottawa scores was found for the mid colon or amount of fluid. Patient satisfaction was similar for both arms but those assigned to 4-L SF-PEG reported less bloating: 23.1% vs 11.5% (P = 0.0235). Overall polyp detection, adenomatous polyp and advanced adenoma detection rates were similar between the two groups. CONCLUSION: Morning only 4-L SF-PEG provided superior cleansing with less bloating as compared to 2-L PEG + Asc bowel preparation for afternoon colonoscopy. Thus, future studies evaluating efficacy of morning only preparation for afternoon colonoscopy should use 4-L SF PEG as the standard comparator. PMID- 25132785 TI - Selection of treatment modalities for Budd-Chiari Syndrome in China: a preliminary survey of published literature. AB - AIM: To evaluate the frequency of use of various treatment modalities for Budd Chiari syndrome (BCS) in China by conducting a preliminary survey of relevant literature. METHODS: All papers regarding the treatment of BCS in Chinese patients were identified by searching PubMed, Chinese Scientific and Technological Journal, and China National Knowledge Infrastructure databases. Data regarding the number of BCS patients treated with different treatment modalities over time were collected. The proportions of BCS patients undergoing various treatment modalities were calculated. RESULTS: Overall, 300 of 3005 papers initially retrieved were included. These papers included 23352 BCS patients treated with different treatment modalities. The treatment modalities include surgery (n = 8625), interventional treatment (n = 13940), surgery combined with interventional treatment (n = 363), medical therapy (n = 277), other treatments (n = 91), and no treatment (n = 56). After 2005, the number of BCS patients treated with surgery was drastically decreased, but the number of BCS patients who underwent interventional treatment was almost maintained. Shunt surgery was the most common type of surgery (n = 3610). Liver transplantation was rarely employed (n = 2). Balloon angioplasty with or without stenting was the most common type of interventional treatment (n = 13747). Transjugular intrahepatic portosystemic shunt was rarely employed (n = 81). CONCLUSION: Selection of treatment modalities for BCS might be different between China and Western countries. Further work should be necessary to establish a unanimous therapeutic strategy for BCS in China. PMID- 25132786 TI - Symptomatic multinodular splenic hamartoma preoperatively suspected as metastatic tumor: a case report. AB - Splenic hamartoma (SH) is a rare benign tumor usually detected accidentally, which is composed of an aberrant mixture of normal splenic elements. Here, we report a case of 54-year-old man who presented with symptomatic multinodular SH and was admitted initially for thrombocytopenia and anemia. Physical examination revealed that the patients had an anemic appearance and palpable spleen, extending 10 cm below the costal margin. Preoperative ultrasound and computed tomography (CT) indicated splenomegaly with multinodular lesions. On enhanced CT scanning, during the arterial phase, the lesions demonstrated inhomogeneous enhancement, and in the portal phase the lesions were more hyperdense than the splenic parenchyma. The images were highly suggestive of a metastatic tumor. Splenectomy was performed 1 wk later. The tumor was eventually diagnosed as SH according to the morphological features and immunohistochemical detection, by which CD34 was positive in lining cells and some spindle cells, vimentin was positive in the tumor, factor-VIII-related antigen was positive multifocally in lining cells, and smooth muscle actin was positive in some spindle cells. Thrombocytopenia and anemia were cured after splenectomy. PMID- 25132788 TI - Collaborative work between the West and Asia. AB - The "Collaborative Work between the West and Asia" session was chaired by Dr. Yih Ing Hser and had three speakers. The speakers (and their topics) were: Dr. Gavin Bart (Collaborative Addiction Research in Asian Populations Home and Abroad), Dr. Li Li (Implementing Intervention Research Projects in Asia), and Dr. Le Minh Giang (Building Research Infrastructure for International Collaborative Studies on Substance Use Disorder and HIV: The Case of Hanoi Medical University/Vietnam). PMID- 25132787 TI - Acute acalculous cholecystitis immediately after gastric operation: case report and literatures review. AB - Acute acalculous cholecystitis (AAC) is a rare complication of gastric surgery. The most commonly accepted concepts regarding its pathogenesis are bile stasis, sepsis and ischemia, but it has not been well described how to identify and manage this disease in the early stage. We report three cases of AAC in elderly patients immediately after gastric surgery, which were treated with three different strategies. One patient died 42 d after emergency cholecystectomy, and the other two finally recovered through timely cholecystostomy and percutaneous transhepatic gallbladder drainage, respectively. These cases informed us of the value of early diagnosis and proper treatment for perioperative AAC after gastric surgery. We further reviewed reported cases of AAC immediately after gastric operation, which may expand our knowledge of this disease. PMID- 25132789 TI - Synthesis, central nervous system activity, and structure-activity relationship of 1-aryl-6-benzyl-7-hydroxy-2,3-dihydroimidazo[1,2-a]pyrimidine-5(1H)-ones. AB - A series of 24 1-aryl-6-benzyl-7-hydroxy-2,3-dihydroimidazo[1,2-a]pyrimidine 5(1H)-ones was designed as antinociceptive compounds acting through opioid receptors with additional serotoninergic activity. The compounds, similarly as previously published series, lack the protonable nitrogen atom which is a part of classical opioid receptor pharmacophore and is necessary to interact with the conserved Asp(3.32) in the opioid receptor binding pocket. The compounds were obtained in one-step cyclocondensation of 1-aryl-4,5-dihydro-1H-imidazol-2-amines diethyl 2-benzylmalonate or diethyl 2-(2-chlorobenzyl)malonate under basic conditions. Almost all the tested compounds exerted strong antinociceptive activity, but surprisingly, it was not reversed by naloxone; thus, it is not mediated through opioid receptors. It makes it possible to conclude that addition of one more aromatic moiety to the non-classical opioid receptor pharmacophore results in the compounds which are not opioid receptor ligands. The lack of activity of one of the tested compounds may be attributed to low blood-brain barrier permeation or unfavorable distribution of electrostatic potential and HOMO and LUMO orbitals. PMID- 25132790 TI - THE RELATIONSHIP BETWEEN MALE-PERPETRATED INTERPARENTAL AGGRESSION, PATERNAL CHARACTERISTICS, AND CHILD PSYCHOSOCIAL FUNCTIONING. AB - It is well established that children in homes where interparental violence is present are at increased risk for psychosocial (i.e., internalizing, externalizing, and attention) difficulties. However, previous studies have provided a limited view on the variety of factors that commonly co-occur in these environments (e.g., other characteristics of the parents and family) and how they may collectively impact children. Knowing this information could have implications for parental interventions aimed at preventing the continuation or initiation of psychosocial problems in children. Thus, the present study simultaneously examined the association between father-perpetrated interparental aggression, father characteristics, and child psychosocial functioning in a sample of 145 men arrested for domestic violence. Results showed that of all the variables examined, paternal antisocial personality traits and interpersonal hostility were uniquely associated with overall child psychosocial impairment, externalizing problems, and attention problems. Implications for intervention programs are discussed. PMID- 25132791 TI - Robust measurement of individual localized changes to the aging hippocampus. AB - Alzheimer's Disease (AD) is characterized by a stereotypical spatial pattern of hippocampus (HP) atrophy over time, but reliable and precise measurement of localized longitudinal change to individual HP in AD have been elusive. We present a method for quantifying subject-specific spatial patterns of longitudinal HP change that aligns serial HP surface pairs together, cuts slices off the ends of the HP that were not shared in the two delineations being aligned, estimates weighted correspondences between baseline and follow-up HP, and finds a concise set of localized spatial change patterns that explains HP changes while down-weighting HP surface points whose estimated changes are biologically implausible. We tested our method on a synthetic HP change dataset as well as a set of 320 real elderly HP measured at 1-year intervals. Our results suggests that the proposed steps reduce the amount of implausible HP changes indicated among individual HP, increase the strength of association between HP change and cognitive function related to AD, and enhance the estimation of reliable spatially-localized HP change patterns. PMID- 25132792 TI - ISOLATION OF GLYCOSIDES FROM THE BARKS OF ILEX ROTUNDA BY HIGH-SPEED COUNTER CURRENT CHROMATOGRAPHY. AB - Semi-preparative and preparative high-speed counter-current chromatography (HSCCC) were successfully used for isolation of glycosides from 50% ethanol extract of the dried barks of Ilex rotunda Thunb. (Aquifoliaceae) by using a two phase solvent system composed of ethyl acetate-n-butanol-water (1:6:7, v/v/v). From 1.0 g of the extract, syringaresinol 4',4"-di-o-beta-d-glucopyranoside (I, 20.2 mg),, syringin (II, 56.8 mg), sinapaldehyde glucoside (III, 26.2 mg),, syringaresinol 4'-o-beta-d-glucopyranoside (IV, 20.4 mg), and pedunculoside (V, 45.1 mg) were obtained by one run of TBE-1000A HSCCC instrument with 1000 mL of column volume. Their structures were identified by IR, MS, and 1H and 13C NMR studies. Glycoside I was isolated from this plant for the first time. PMID- 25132793 TI - Disclosure of Positive BRCA1/2-Mutation Status in Young Couples: The Journey From Uncertainty to Bonding Through Partner Support. AB - BRCA1/2-positive women who learn their mutation status early in the life-course face unique challenges related to navigating the tasks of young adulthood. Using qualitative methods and grounded theory, the authors analyzed in-depth interviews with 11 women aged 26 to 35 who learned their mutation status before marriage. Their narratives illustrate the complexity of relationship formation, and highlight the potential for relationship-bonding and intimacy-building in the course of sharing mutation information. Disclosing BRCA mutation status to dating partners is often preceded by feelings of fear and anxiety, yet many participants reported that doing so has positive effects on relationships. Partners' abilities to respond with interest, empathy, and affection are associated with in creased future intimacy, consistent with generally accepted principles within the family/couple systems field. Individual cancer risk perception and familial cancer experiences may affect the disclosure experience, which can be understood via Attachment Theory. Our findings provide clinical insight, identify new areas for research, and suggest ways to assist this unique population in their adjustment to being BRCA mutation-positive. PMID- 25132794 TI - Spatial Resolution Requirements for Traffic-Related Air Pollutant Exposure Evaluations. AB - Vehicle emissions represent one of the most important air pollution sources in most urban areas, and elevated concentrations of pollutants found near major roads have been associated with many adverse health impacts. To understand these impacts, exposure estimates should reflect the spatial and temporal patterns observed for traffic-related air pollutants. This paper evaluates the spatial resolution and zonal systems required to estimate accurately intraurban and near road exposures of traffic-related air pollutants. The analyses use the detailed information assembled for a large (800 km2) area centered on Detroit, Michigan, USA. Concentrations of nitrogen oxides (NOx) due to vehicle emissions were estimated using hourly traffic volumes and speeds on 9,700 links representing all but minor roads in the city, the MOVES2010 emission model, the RLINE dispersion model, local meteorological data, a temporal resolution of 1 hr, and spatial resolution as low as 10 m. Model estimates were joined with the corresponding shape files to estimate residential exposures for 700,000 individuals at property parcel, census block, census tract, and ZIP code levels. We evaluate joining methods, the spatial resolution needed to meet specific error criteria, and the extent of exposure misclassification. To portray traffic-related air pollutant exposure, raster or inverse distance-weighted interpolations are superior to nearest neighbor approaches, and interpolations between receptors and points of interest should not exceed about 40 m near major roads, and 100 m at larger distances. For census tracts and ZIP codes, average exposures are overestimated since few individuals live very near major roads, the range of concentrations is compressed, most exposures are misclassified, and high concentrations near roads are entirely omitted. While smaller zones improve performance considerably, even block-level data can misclassify many individuals. To estimate exposures and impacts of traffic-related pollutants accurately, data should be geocoded or estimated at the most-resolved spatial level; census tract and larger zones have little if any ability to represent intraurban variation in traffic-related air pollutant concentrations. These results are based on one of the most comprehensive intraurban modeling studies in the literature and results are robust. Recommendations address the value of dispersion models to portray spatial and temporal variation of air pollutants in epidemiology and other studies; techniques to improve accuracy and reduce the computational burden in urban scale modeling; the necessary spatial resolution for health surveillance, demographic, and pollution data; and the consequences of low resolution data in terms of exposure misclassification. PMID- 25132796 TI - Endogenous retroviruses in domestic animals. AB - Endogenous retroviruses (ERVs) are genomic elements that are present in a wide range of vertebrates. Although the study of ERVs has been carried out mainly in humans and model organisms, recently, domestic animals have become important, and some species have begun to be analyzed to gain further insight into ERVs. Due to the availability of complete genomes and the development of new computer tools, ERVs can now be analyzed from a genome-wide viewpoint. In addition, more experimental work is being carried out to analyze the distribution, expression and interplay of ERVs within a host genome. Cats, cattle, chicken, dogs, horses, pigs and sheep have been scrutinized in this manner, all of which are interesting species in health and economic terms. Furthermore, several studies have noted differences in the number of endogenous retroviruses and in the variability of these elements among different breeds, as well as their expression in different tissues and the effects of their locations, which, in some cases, are near genes. These findings suggest a complex, intriguing relationship between ERVs and host genomes. In this review, we summarize the most important in silico and experimental findings, discuss their implications and attempt to predict future directions for the study of these genomic elements. PMID- 25132797 TI - Using current data to define new approach in age related macular degeneration: need to accelerate translational research. AB - Age related macular degeneration (AMD) is one of the major retinal degenerative disease of ageing whose complex genetic basis remains undeciphered. The involvement of various other factors like mitochondrial genes, cytoskeletal proteins and the role of epigenetics has been described in this review. Several population based AMD genetic studies have been carried out worldwide. Despite the increased publication of reports, clinical translation still eludes this davastating disease. We suggest models to address roadblocks in clinical translation hoping that these would be beneficial to drive AMD research towards innovative biomarkers and therapeutics Therefore, addressing the need large autopsy studies and combining it with efficient use of bioinformatic tools, statistical modeling and probing SNP-biomarker association are key to time bound resolution of this disease. PMID- 25132795 TI - Spatial and temporal simulation of human evolution. Methods, frameworks and applications. AB - Analyses of human evolution are fundamental to understand the current gradients of human diversity. In this concern, genetic samples collected from current populations together with archaeological data are the most important resources to study human evolution. However, they are often insufficient to properly evaluate a variety of evolutionary scenarios, leading to continuous debates and discussions. A commonly applied strategy consists of the use of computer simulations based on, as realistic as possible, evolutionary models, to evaluate alternative evolutionary scenarios through statistical correlations with the real data. Computer simulations can also be applied to estimate evolutionary parameters or to study the role of each parameter on the evolutionary process. Here we review the mainly used methods and evolutionary frameworks to perform realistic spatially explicit computer simulations of human evolution. Although we focus on human evolution, most of the methods and software we describe can also be used to study other species. We also describe the importance of considering spatially explicit models to better mimic human evolutionary scenarios based on a variety of phenomena such as range expansions, range shifts, range contractions, sex-biased dispersal, long-distance dispersal or admixtures of populations. We finally discuss future implementations to improve current spatially explicit simulations and their derived applications in human evolution. PMID- 25132798 TI - Temporally and spatially restricted gene expression profiling. AB - Identifying gene function in specific cells is critical for understanding the processes that make cells unique. Several different methods are available to isolate actively transcribed RNA or actively translated RNA in specific cells at a chosen time point. Cell-specific mRNA isolation can be accomplished by the expression of transgenes in cells of interest, either directly from a specific promoter or using a modular system such as Gal4/UAS or Cre/lox. All of the methods described in this review, namely thiol-labeling of RNA (TU-tagging or RABT), TRAP (translating ribosome affinity purification) and INTACT (isolation of nuclei tagged in specific cell types), allow next generation sequencing, permitting the identification of enriched gene transcripts within the specific cell-type. We describe here the general concept of each method, include examples, evaluate possible problems related to each technique, and suggest the types of questions for which each method is best suited. PMID- 25132801 TI - Electron Cryo-Microscopy Studies of Helminthosporium victoriae Virus 190S. PMID- 25132799 TI - Impact of next generation sequencing techniques in food microbiology. AB - Understanding the Maxam-Gilbert and Sanger sequencing as the first generation, in recent years there has been an explosion of newly-developed sequencing strategies, which are usually referred to as next generation sequencing (NGS) techniques. NGS techniques have high-throughputs and produce thousands or even millions of sequences at the same time. These sequences allow for the accurate identification of microbial taxa, including uncultivable organisms and those present in small numbers. In specific applications, NGS provides a complete inventory of all microbial operons and genes present or being expressed under different study conditions. NGS techniques are revolutionizing the field of microbial ecology and have recently been used to examine several food ecosystems. After a short introduction to the most common NGS systems and platforms, this review addresses how NGS techniques have been employed in the study of food microbiota and food fermentations, and discusses their limits and perspectives. The most important findings are reviewed, including those made in the study of the microbiota of milk, fermented dairy products, and plant-, meat- and fish derived fermented foods. The knowledge that can be gained on microbial diversity, population structure and population dynamics via the use of these technologies could be vital in improving the monitoring and manipulation of foods and fermented food products. They should also improve their safety. PMID- 25132802 TI - Public discourse on HIV/AIDS: an archival analysis of national newspaper reporting in Uganda, 1996-2011. AB - Uganda is recognised as an early success story in the HIV epidemic at least in part due to an open and vigorous national dialogue about HIV prevention. This study examined the national discourse about HIV, AIDS, and young people in New Vision, Uganda's leading national newspaper between 1996 and 2011, building from a previous archival analysis of New Vision reporting by Kirby (1986-1995). We examined the continuing evolution in the public discourse in Uganda, focusing on reporting about young people. An increase in reporting on HIV and AIDS occurred after 2003, as antiretroviral treatment was becoming available. While the emphasis in newspaper reporting about adults and the population at large evolved to reflect the development of new HIV treatment and prevention methods, the majority of the articles focused on young people did not change. Articles about young people continued to emphasise HIV acquisition due to early and premarital sexual activity and the need for social support services for children affected by HIV and AIDS. Articles often did not report on the complex social conditions that shape HIV-related risk among young people, or address young people who are sexually active, married, and/or HIV infected. With HIV prevalence now increasing among young people and adults in Uganda, greater attention to HIV prevention is needed. PMID- 25132800 TI - A Comprehensive Review of Dysregulated miRNAs Involved in Cervical Cancer. AB - MicroRNAs(miRNAs) have become the center of interest in oncology. In recent years, various studies have demonstrated that miRNAs regulate gene expression by influencing important regulatory genes and thus are responsible for causing cervical cancer. Cervical cancer being the third most diagnosed cancer among the females worldwide, is the fourth leading cause of cancer related mortality. Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests, combined with traditional Pap test screening have greatly reduced cervical cancer. Yet, thousands of women continue to be diagnosed with and die of this preventable disease annually. This has necessitated the scientists to ponder over ways of evolving new methods and chalk out novel treatment protocols/strategies. As miRNA deregulation plays a key role in malignant transformation of cervical cancer along with its targets that can be exploited for both prognostic and therapeutic strategies, we have collected and reviewed the role of miRNA in cervical cancer. A systematic search was performed using PubMed for articles that report aberrant expression of miRNA in cervical cancer. The present review provides comprehensive information for 246 differentially expressed miRNAs gathered from 51 published articles that have been implicated in cervical cancer progression. Of these, more than 40 miRNAs have been reported in the literature in several instances signifying their role in the regulation of cancer. We also identified 40 experimentally validated targets, studied the cause of miRNAs dysregulation along with its mechanism and role in different stages of cervical cancer. We also identified and analysed miRNA clusters and their expression pattern in cervical cancer. This review is expected to further enhance our understanding in this field and serve as a valuable reference resource. PMID- 25132804 TI - Eating fish for two. AB - This article is based on the British Nutrition Foundation's Annual Lecture, which focused on maternal fish consumption and the effects of methylmercury (MeHg) on fetal development, with respect to current guidance and policy on fish consumption during pregnancy. Fish makes a valuable contribution to nutrient intakes across the globe and is the primary protein source for many individuals, particularly those in the developing world. Populations with a high fish consumption, such as in the Republic of the Seychelles, have a greater exposure to MeHg, which is present in varying amounts in all fish. Methylmercury is a toxic pollutant, which is known to impair neurodevelopment. The dose of MeHg from fish consumption, however, needed to impair neurodevelopment is unknown. Current UK and US guidance on fish consumption during pregnancy tend to focus more on avoiding risks rather than highlighting the benefits which can be obtained from eating fish. Such recommendations have been mainly based on data arising from epidemiological studies in the Faroe Islands, where methylmercury exposure was largely from pilot whale consumption. Although small adverse effects on child development have been reported in data from the Faroe Islands, data from the on going Seychelles Child Development Studies have shown no adverse effects of prenatal methlymercury exposure from high maternal fish consumption (9-12 meals containing fish per week) on developmental outcomes. Instead these data suggest that nutrients, including long chain polyunsaturated fatty acids (LC-PUFAs), provided by fish may offer a beneficial effect and attenuate or modify any effects of MeHg on developmental outcomes. Recent expert consultations have concluded that the health benefits of fish consumption outweigh the risks posed by MeHg exposure and have argued the need for improved education and guidance to highlight the importance of consuming nutrients, including LC-PUFAs, from fish for optimal child development and to encourage fish consumption during pregnancy. PMID- 25132803 TI - Effect of ischemic and pharmacological preconditioning of lower limb muscle tissue on tissue oxygenation measured by near-infrared spectroscopy--a pilot study. AB - BACKGROUND: Ischemic or volatile anesthetic preconditioning is defined as tissue protection from impending ischemic cell damage by repetitive short periods of tissue exposure to ischemia or volatile anesthetics. Objective of this study was to elucidate, if ischemic preconditioning and pharmacological preconditioning with sevoflurane have effects on muscle tissue oxygen saturation in patients undergoing surgical revascularization of the lower limb. METHODS: In this prospective randomized pilot study ischemic and pharmacological (sevoflurane) preconditioning was performed in 40 patients with lower limb arterial occlusive disease undergoing surgical revascularization. Sevoflurane preconditioning was performed in one group (N = 20) by repetitive application of sevoflurane for six minutes interspersed by six minutes of washout. Thereafter, ischemic preconditioning was performed in all patients (N = 40) by repetitive clamping of the femoral artery for six minutes interspersed by six minutes of reperfusion. The effect of both procedures on leg muscle tissue oxygen saturation (rSO2) was measured by near-infrared spectroscopy during both procedures and during surgery and reperfusion (INVOS(r) 5100C Oxymeter with Small Adult SomaSensor(r) SAFB-SM, Somanetics, Troy, Michigan, USA). RESULTS: Repetitive clamping and reperfusion of the femoral artery resulted in significant cyclic decrease and increase of muscle rSO2 (p < 0.0001). Pharmacological preconditioning with sevoflurane resulted in a faster and higher increase of rSO2 during postoperative reperfusion (Maximal 111% baseline +/- 20 versus 103% baseline +/- 14, p = 0.008) consistent with an additional effect of pharmacological preconditioning on leg perfusion. CONCLUSIONS: Ischemic preconditioning of lower limb muscle tissue and pharmacological preconditioning with sevoflurane have an effect on tissue oxygenation in patients with lower limb occlusive arterial disease. TRIAL REGISTRATION: The trial has been registrated at http://www.ClinicalTrial.gov, TRIAL NUMBER: NCT02038062 at 14 January 2014. PMID- 25132805 TI - Facilitators and barriers influencing patient safety in Swedish hospitals: a qualitative study of nurses' perceptions. AB - BACKGROUND: Sweden has undertaken many national, regional, and local initiatives to improve patient safety since the mid-2000s, but solid evidence of effectiveness for many solutions is often lacking. Nurses play a vital role in patient safety, constituting 71% of the workforce in Swedish health care. This interview study aimed to explore perceived facilitators and barriers influencing patient safety among nurses involved in the direct provision of care. Considering the importance of nurses with regard to patient safety, this knowledge could facilitate the development and implementation of better solutions. METHODS: A qualitative study with semi-structured individual interviews was carried out. The study population consisted of 12 registered nurses at general hospitals in Sweden. Data were analyzed using qualitative content analysis. RESULTS: The nurses identified 22 factors that influenced patient safety within seven categories: 'patient factors', 'individual staff factors', 'team factors', 'task and technology factors', 'work environment factors', 'organizational and management factors', and 'institutional context factors'. Twelve of the 22 factors functioned as both facilitators and barriers, six factors were perceived only as barriers, and four only as facilitators. There were no specific patterns showing that barriers or facilitators were more common in any category. CONCLUSION: A broad range of factors are important for patient safety according to registered nurses working in general hospitals in Sweden. The nurses identified facilitators and barriers to improved patient safety at multiple system levels, indicating that complex multifaceted initiatives are required to address patient safety issues. This study encourages further research to achieve a more explicit understanding of the problems and solutions to patient safety. PMID- 25132807 TI - Separating Octadecyltrimethoxysilane Hydrolysis and Condensation at the Air/Water Interface through Addition of Methyl Stearate. AB - The hydrolysis and condensation of octadecyltrimethoxysilane (OTMS) at the air/water interface were monitored through molecular area changes at a constant surface pressure of 10 mN/m. The onset of condensation was delayed through the addition of methyl stearate (SME) acting as an inert filler molecule. In the absence of SME, complete gelation of OTMS required 30 h, during which time OTMS condensation occurred concomitantly with hydrolysis. In the presence of SME, the OTMS monolayer gelation rate increased in proportion to the amount of SME present. A 1:6 OTMS:SME molar ratio resulted in monolayer gelation within 30 min, suggesting completion of monomer hydrolysis prior to condensation. These findings indicate that lability of OTMS to hydrolysis at the air/water interface is governed by steric and conformational constraints at the silicon atom site, with monomeric OTMS being much more reactive than oligomeric OTMS. Fluorescence microscope images demonstrated that the OTMS condensed domain size also decreased with increasing SME concentrations, further implicating SME's role as an inert filler. PMID- 25132806 TI - Decreased percentage of CD4(+)Foxp3(+)TGF-beta(+) and increased percentage of CD4(+)IL-17(+) cells in bronchoalveolar lavage of asthmatics. AB - BACKGROUND: Asthma is a chronic inflammatory disorder of the airways with the proven role of Th2 cells in its pathogenesis. The role and characteristic of different subsets of CD4(+) cells is much less known. AIM: The aim of the study was to analyze the incidence of different subsets of CD4(+) T cells, in particular different subsets of CD4(+) cells with the co-expression of different cytokines. METHODS: Twenty five stable asthmatic and twelve age-matched control subjects were recruited to the study. Bronchoscopy and bronchoalveolar lavage (BAL) were performed in all study subjects. CD4(+) T cells were isolated from BAL fluid by positive magnetic selection. After stimulation simultaneous expression of TGF-beta, FoxP3, CD25, IFN-gamma, IL-4, TNF-alpha (set 1); IL-10, FoxP3, CD25, IFN-gamma, IL-4, MIP-1beta (set 2); IL-17A, IL-8, IFN-gamma, IL-4, MIP-1beta (set 3) were measured by flow cytometry. RESULTS: The percentage of CD4(+) cells co expressing Foxp3 and TGF-beta (CD4(+)Foxp3(+)TGF-beta(+) cells) was significantly lower (P = 0.03), whereas the percentage of CD4(+)IL-17(+) cells (P = 0.008), CD4(+)IL-17(+) IFN-gamma(+) cells (P = 0.047) and CD4(+)IL-4(+) cells (P = 0.01) were significantly increased in asthmatics compared with that seen in healthy subjects. A significantly higher percentage of CD4(+)Foxp3(+) cells from asthma patients expressed IFN-gamma (P = 0.01), IL-4 (P = 0.004) and CD25 (P = 0.04), whereas the percentage of CD4(+)IL-10(+) cells expressing Foxp3 was significantly decreased in asthmatics (P = 0.03). FEV1% predicted correlated negatively with the percentage of CD4(+)IL-17(+) cells (r = -0.33; P = 0.046) and positively with CD4(+)Foxp3(+)TGF-beta(+) cells (r = 0.43; P = 0.01). CONCLUSIONS: Our results suggest that in the airways of chronic asthma patients there is an imbalance between increased numbers of CD4(+)IL-17(+) cells and Th2 cells and decreased number of CD4(+)Foxp3(+)TGF-beta(+). PMID- 25132808 TI - MRI-Derived 3-D-Printed Breast Phantom for Microwave Breast Imaging Validation. AB - We propose a 3-D-printed breast phantom for use in preclinical experimental microwave imaging studies. The phantom is derived from an MRI of a human subject; thus, it is anthropomorphic, and its interior is very similar to an actual distribution of fibroglandular tissues. Adipose tissue in the breast is represented by the solid plastic (printed) regions of the phantom, while fibroglandular tissue is represented by liquid-filled voids in the plastic. The liquid is chosen to provide a biologically relevant dielectric contrast with the printed plastic. Such a phantom enables validation of microwave imaging techniques. We describe the procedure for generating the 3-D-printed breast phantom and present the measured dielectric properties of the 3-D-printed plastic over the frequency range 0.5-3.5 GHz. We also provide an example of a suitable liquid for filling the fibroglandular voids in the plastic. PMID- 25132810 TI - On the Existence and Uniqueness of the Scientific Method. AB - The ultimate utility of science is widely agreed upon: the comprehension of reality. But there is much controversy about what scientific understanding actually means, and how we should proceed in order to gain new scientific understanding. Is there a method for acquiring new scientific knowledge? Is this method unique and universal? There has been no shortage of proposals, but neither has there been a shortage of skeptics about these proposals. This article proffers for discussion a potential scientific method that aspires to be unique and universal and is rooted in the recent and ancient history of scientific thinking. Curiously, conclusions can be inferred from this scientific method that also concern education and the transmission of science to others. PMID- 25132809 TI - L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy. AB - BACKGROUND: The purpose of this study was to examine if L-leucine (Leu), beta hydroxy-beta-methylbutyrate (HMB), or creatine monohydrate (Crea) prevented potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes. METHODS: After four days of differentiation, myotubes were treated with MSTN (10 ng/ml) for two additional days and four treatment groups were studied: 1) 3x per day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea, 4) DM only. Myotubes treated with DM without MSTN were analyzed as the control condition (DM/CTL). Following treatment, cells were analyzed for total protein, DNA content, RNA content, muscle protein synthesis (MPS, SUnSET method), and fiber diameter. Separate batch treatments were analyzed for mRNA expression patterns of myostatin-related genes (Akirin-1/Mighty, Notch-1, Ski, MyoD) as well as atrogenes (MuRF-1, and MAFbx/Atrogin-1). RESULTS: MSTN decreased fiber diameter approximately 30% compared to DM/CTL myotubes (p < 0.001). Leu, HMB and Crea prevented MSTN-induced atrophy. MSTN did not decrease MPS levels compared to DM/CTL myotubes, but MSTN treatment decreased the mRNA expression of Akirin 1/Mighty by 27% (p < 0.001) and MyoD by 26% (p < 0.01) compared to DM/CTL myotubes. shRNA experiments confirmed that Mighty mRNA knockdown reduced myotube size, linking MSTN treatment to atrophy independent of MPS. Remarkably, MSTN + Leu and MSTN + HMB myotubes had similar Akirin-1/Mighty and MyoD mRNA levels compared to DM/CTL myotubes. Furthermore, MSTN + Crea myotubes exhibited a 36% (p < 0.05) and 86% (p < 0.001) increase in Akirin-1/Mighty mRNA compared to DM/CTL and MSTN-only treated myotubes, respectively. CONCLUSIONS: Leu, HMB and Crea may reduce MSTN-induced muscle fiber atrophy by influencing Akirin-1/Mighty mRNA expression patterns. Future studies are needed to examine if Leu, HMB and Crea independently or synergistically affect Akirin-1/Mighty expression, and how Akirin-1/Mighty expression mechanistically relates to skeletal muscle hypertrophy in vivo. PMID- 25132811 TI - Silicon/organic hybrid heterojunction infrared photodetector operating in the telecom regime. AB - The authors report on the fabrication of a silicon/organic heterojunction based IR photodetector. It is demonstrated that an Al/p-Si/perylene-derivative/Al heterostructure exhibits a photovoltaic effect up to 2.7 MUm (0.46 eV), a value significantly lower than the bandgap of either material. Although the devices are not optimized, at room temperature a rise time of 300 ns, a responsivity of ~0.2 mA/W with a specific detectivity of D* ~ 7 * 107 Jones at 1.55 MUm is found. The achieved responsivity is two orders of magnitude higher compared to our previous efforts [1,2]. It will be outlined that the photocurrent originates from an absorption mechanism involving excitation of an electron from the Si valence band into the extended LUMO state in the perylene-derivative, with possible participation of intermediate localized surface state in the organic material. The non-invasive deposition of the organic interlayer onto the Si results in compatibility with the CMOS process, making the presented approach a potential alternative to all inorganic device concepts. PMID- 25132812 TI - Jumping on the Train of Personalized Medicine: A Primer for Non-Geneticist Clinicians: Part 1. Fundamental Concepts in Molecular Genetics. AB - With the decrease in sequencing cost and the rise of companies providing sequencing services, it is likely that personalized whole-genome sequencing will eventually become an instrument of common medical practice. We write this series of three reviews to help non-geneticist clinicians get ready for the major breakthroughs that are likely to occur in the coming years in the fast-moving field of personalized medicine. This first paper focuses on the fundamental concepts of molecular genetics. We review how recombination occurs during meiosis, how de novo genetic variations including single nucleotide polymorphisms (SNPs), insertions and deletions are generated and how they are inherited from one generation to the next. We detail how genetic variants can impact protein expression and function, and summarize the main characteristics of the human genome. We also explain how the achievements of the Human Genome Project, the HapMap Project, and more recently, the 1000 Genomes Project, have boosted the identification of genetic variants contributing to common diseases in human populations. The second and third papers will focus on genetic epidemiology and clinical applications in personalized medicine. PMID- 25132813 TI - Gender effects and sexual-orientation impact on androstadienone-evoked behavior and neural processing. AB - In humans, the most established and investigated substance acting as a chemosignal, i.e., a substance that is excreted from the body, is 4,16 androstadien-3-one (AND). AND, which is found in sweat and saliva, is known to be responsible for influencing several variables, such as psychophysiological status, behavior, as well as cortical processing. The aim of the present review is to give insight into the variety of AND effects, with special regard to specific cross-sexual characteristics of this putative human chemosignal, emphasizing the neural activation patterns and factors such as contextual conditions. This review highlights the importance of including those contributing factors into the analysis of behavioral as well as brain-related studies. PMID- 25132815 TI - Quantification of a secondary task-specific tremor in a violinist after a temporal lobectomy. AB - Task-specific tremors (TSTs) occur mainly during certain tasks and may be highly disabling. In this case study, we report on a 66-year-old violinist who developed a TST of the right arm only while playing the violin 4 weeks after a temporal lobectomy, which had been performed as a result of his temporal lobe epilepsy. Since a similar case, to our knowledge, has not been reported so far, our aim was to quantitatively assess and describe the tremor by measuring (a) the electromyography (EMG) activity of the wrist flexor and extensor as well as (b) an accelerometer signal of the hand. We found a tremor-related frequency of about 7 Hz. Furthermore, at a similar frequency of about 7 Hz, there was coherence between the tremor acceleration and EMG-activity of the wrist flexor and extensor as well as between the tremor acceleration and coactivation. The tremorgenesis remains unclear, and possible explanations can only be speculative. PMID- 25132816 TI - Understanding human perception by human-made illusions. AB - IT MAY BE FUN TO PERCEIVE ILLUSIONS, BUT THE UNDERSTANDING OF HOW THEY WORK IS EVEN MORE STIMULATING AND SUSTAINABLE: They can tell us where the limits and capacity of our perceptual apparatus are found-they can specify how the constraints of perception are set. Furthermore, they let us analyze the cognitive sub-processes underlying our perception. Illusions in a scientific context are not mainly created to reveal the failures of our perception or the dysfunctions of our apparatus, but instead point to the specific power of human perception. The main task of human perception is to amplify and strengthen sensory inputs to be able to perceive, orientate and act very quickly, specifically and efficiently. The present paper strengthens this line of argument, strongly put forth by perceptual pioneer Richard L. Gregory (e.g., Gregory, 2009), by discussing specific visual illusions and how they can help us to understand the magic of perception. PMID- 25132817 TI - Inter-individual cognitive variability in children with Asperger's syndrome. AB - Multiple studies have tried to establish the distinctive profile of individuals with Asperger's syndrome (AS). However, recent reports suggest that adults with AS feature heterogeneous cognitive profiles. The present study explores inter individual variability in children with AS through group comparison and multiple case series analysis. All participants completed an extended battery including measures of fluid and crystallized intelligence, executive functions, theory of mind, and classical neuropsychological tests. Significant group differences were found in theory of mind and other domains related to global information processing. However, the AS group showed high inter-individual variability (both sub- and supra-normal performance) on most cognitive tasks. Furthermore, high fluid intelligence correlated with less general cognitive impairment, high cognitive flexibility, and speed of motor processing. In light of these findings, we propose that children with AS are characterized by a distinct, uneven pattern of cognitive strengths and weaknesses. PMID- 25132814 TI - The ubiquitin-proteasome system in neurodegenerative diseases: precipitating factor, yet part of the solution. AB - The ubiquitin-proteasome system (UPS) has been implicated in neurodegenerative diseases based on the presence of deposits consisting of ubiquitylated proteins in affected neurons. It has been postulated that aggregation-prone proteins associated with these disorders, such as alpha-synuclein, beta-amyloid peptide, and polyglutamine proteins, compromise UPS function, and delay the degradation of other proteasome substrates. Many of these substrates play important regulatory roles in signaling, cell cycle progression, or apoptosis, and their inadvertent stabilization due to an overloaded and improperly functioning UPS may thus be responsible for cellular demise in neurodegeneration. Over the past decade, numerous studies have addressed the UPS dysfunction hypothesis using various model systems and techniques that differ in their readout and sensitivity. While an inhibitory effect of some disease proteins on the UPS has been demonstrated, increasing evidence attests that the UPS remains operative in many disease models, which opens new possibilities for treatment. In this review, we will discuss the paradigm shift that repositioned the UPS from being a prime suspect in the pathophysiology of neurodegeneration to an attractive therapeutic target that can be harnessed to accelerate the clearance of disease-linked proteins. PMID- 25132818 TI - The neural architecture of age-related dual-task interferences. AB - In daily life elderly adults exhibit deficits when dual-tasking is involved. So far these deficits have been verified on a behavioral level in dual-tasking. Yet, the neuronal architecture of these deficits in aging still remains to be explored especially when late-middle aged individuals around 60 years of age are concerned. Neuroimaging studies in young participants concerning dual-tasking were, among others, related to activity in middle frontal (MFG) and superior frontal gyrus (SFG) and the anterior insula (AI). According to the frontal lobe hypothesis of aging, alterations in these frontal regions (i.e., SFG and MFG) might be responsible for cognitive deficits. We measured brain activity using fMRI, while examining age-dependent variations in dual-tasking by utilizing the PRP (psychological refractory period) test. Behavioral data showed an increasing PRP effect in late-middle aged adults. The results suggest the age-related deteriorated performance in dual-tasking, especially in conditions of risen complexity. These effects are related to changes in networks involving the AI, the SFG and the MFG. The results suggest that different cognitive subprocesses are affected that mediate the observed dual-tasking problems in late-middle aged individuals. PMID- 25132819 TI - Inhibiting lung lining fluid glutathione metabolism with GGsTop as a novel treatment for asthma. AB - Asthma is characterized by airway inflammation. Inflammation is associated with oxidant stress. Airway epithelial cells are shielded from this stress by a thin layer of lung lining fluid (LLF) which contains an abundance of the antioxidant glutathione. LLF glutathione metabolism is regulated by gamma-glutamyl transferase (GGT). Loss of LLF GGT activity in the mutant GGT(enu1) mouse causes an increase in baseline LLF glutathione content which is magnified in an IL-13 model of allergic airway inflammation and protective against asthma. Normal mice are susceptible to asthma in this model but can be protected with acivicin, a GGT inhibitor. GGT is a target to treat asthma but acivicin toxicity limits clinical use. GGsTop is a novel GGT inhibitor. GGsTop inhibits LLF GGT activity only when delivered through the airway. In the IL-13 model, mice treated with IL-13 and GGsTop exhibit a lung inflammatory response similar to that of mice treated with IL-13 alone. But mice treated with IL-13 and GGsTop show attenuation of methacholine-stimulated airway hyper-reactivity, inhibition of Muc5ac and Muc5b gene induction, decreased airway epithelial cell mucous accumulation and a fourfold increase in LLF glutathione content compared to mice treated with IL-13 alone. Mice treated with GGsTop alone are no different from that of mice treated with saline alone, and show no signs of toxicity. GGsTop could represent a valuable pharmacological tool to inhibit LLF GGT activity in pulmonary disease models. The associated increase in LLF glutathione can protect lung airway epithelial cells against oxidant injury associated with inflammation in asthma. PMID- 25132822 TI - microRNA and skeletal muscle function: novel potential roles in exercise, diseases, and aging. PMID- 25132820 TI - Mitochondrial and cellular mechanisms for managing lipid excess. AB - Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial cellular energetics/redox status is incomplete. Cells store fatty acids (FAs) as triacylglycerol and package them into cytoplasmic lipid droplets (LDs). New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates. Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g., exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain reactive oxygen species (ROS) within levels compatible with signaling while ensuring robust and reliable energy supply. PMID- 25132824 TI - How Traumatic Experiences Leave Their Signature on the Genome: An Overview of Epigenetic Pathways in PTSD. PMID- 25132821 TI - Functional insights into modulation of BKCa channel activity to alter myometrial contractility. AB - The large-conductance voltage- and Ca(2+)-activated K(+) channel (BKCa) is an important regulator of membrane excitability in a wide variety of cells and tissues. In myometrial smooth muscle, activation of BKCa plays essential roles in buffering contractility to maintain uterine quiescence during pregnancy and in the transition to a more contractile state at the onset of labor. Multiple mechanisms of modulation have been described to alter BKCa channel activity, expression, and cellular localization. In the myometrium, BKCa is regulated by alternative splicing, protein targeting to the plasma membrane, compartmentation in membrane microdomains, and posttranslational modifications. In addition, interaction with auxiliary proteins (i.e., beta1- and beta2-subunits), association with G-protein coupled receptor signaling pathways, such as those activated by adrenergic and oxytocin receptors, and hormonal regulation provide further mechanisms of variable modulation of BKCa channel function in myometrial smooth muscle. Here, we provide an overview of these mechanisms of BKCa channel modulation and provide a context for them in relation to myometrial function. PMID- 25132825 TI - Morphometric differences in planum temporale in schizophrenia and bipolar disorder revealed by statistical analysis of labeled cortical depth maps. AB - Differences in cortical thickness in the lateral temporal lobe, including the planum temporale (PT), have been reported in MRI studies of schizophrenia (SCZ) and bipolar disorder (BPD) patients. Most of these studies have used a single valued global or local measure for thickness. However, additional and complementary information can be obtained by generating labeled cortical distance maps (LCDMs), which are distances of labeled gray matter (GM) voxels from the nearest point on the GM/white matter (WM) (inner) cortical surface. Statistical analyses of pooled and censored LCDM distances reveal subtle differences in PT between SCZ and BPD groups from data generated by Ratnanather et al. (Schizophrenia Research, http://dx.doi.org/10.1016/j.schres.2013.08.014). These results confirm that the left planum temporale (LPT) is more sensitive than the right PT in distinguishing between SCZ, BPD, and healthy controls. Also confirmed is a strong gender effect, with a thicker PT seen in males than in females. The differences between groups at smaller distances in the LPT revealed by pooled and censored LCDM analysis suggest that SCZ and BPD have different effects on the cortical mantle close to the GM/WM surface. This is consistent with reported subtle changes in the cortical mantle observed in post-mortem studies. PMID- 25132826 TI - Representational shifts made visible: movement away from the prototype in memory for hue. AB - In four experiments, a total of 205 participants studied individual color patches and were given an old-new recognition test after a brief retention interval (0.5 or 5.0 s). The pattern of hue sensitivity (d') revealed hue memory shifting away from the prototype of the hue's basic color category. The shifts demonstrate that hue memory is influenced by categorization early in processing. The shifts did not depend on intentional categorization; the shifts were found even when participants made preference ratings at encoding rather than labeling judgments. Overall, we found that categorization and memory are deeply intertwined from perception onward. We discuss the impact of the results on theories of memory and categorization, including the effects of category labels on memory (e.g., Lupyan, 2008). We also put forward the hypothesis that atypical shifts in hue are related to atypical shifts that have previously observed in face recognition (Rhodes et al., 1987). PMID- 25132823 TI - Cannabinoid Regulation of Brain Reward Processing with an Emphasis on the Role of CB1 Receptors: A Step Back into the Future. AB - Over the last decades, the endocannabinoid system has been implicated in a large variety of functions, including a crucial modulation of brain-reward circuits and the regulation of motivational processes. Importantly, behavioral studies have shown that cannabinoid compounds activate brain reward mechanisms and circuits in a similar manner to other drugs of abuse, such as nicotine, alcohol, cocaine, and heroin, although the conditions under which cannabinoids exert their rewarding effects may be more limited. Furthermore, there is evidence on the involvement of the endocannabinoid system in the regulation of cue- and drug-induced relapsing phenomena in animal models. The aim of this review is to briefly present the available data obtained using diverse behavioral experimental approaches in experimental animals, namely, the intracranial self-stimulation paradigm, the self-administration procedure, the conditioned place preference procedure, and the reinstatement of drug-seeking behavior procedure, to provide a comprehensive picture of the current status of what is known about the endocannabinoid system mechanisms that underlie modification of brain-reward processes. Emphasis is placed on the effects of cannabinoid 1 (CB1) receptor agonists, antagonists, and endocannabinoid modulators. Further, the role of CB1 receptors in reward processes is investigated through presentation of respective genetic ablation studies in mice. The vast majority of studies in the existing literature suggest that the endocannabinoid system plays a major role in modulating motivation and reward processes. However, much remains to be done before we fully understand these interactions. Further research in the future will shed more light on these processes and, thus, could lead to the development of potential pharmacotherapies designed to treat reward-dysfunction-related disorders. PMID- 25132828 TI - An analysis of post-vocalic /s-?/ neutralization in Augsburg German: evidence for a gradient sound change. AB - The study is concerned with a sound change in progress by which a post-vocalic, pre-consonantal /s-?/ contrast in the standard variety of German (SG) in words such as west/wascht (/vEst/~/vE?t/, west/washes) is influencing the Augsburg German (AG) variety in which they have been hitherto neutralized as /ve?t/. Two of the main issues to be considered are whether the change is necessarily categorical; and the extent to which the change affects both speech production and perception equally. For the production experiment, younger and older AG and SG speakers merged syllables of hypothetical town names to create a blend at the potential neutralization site. These results showed a trend for a progressively greater /s-?/ differentiation in the order older AG, younger AG, and SG speakers. For the perception experiment, forced-choice responses were obtained from the same subjects who had participated in the production experiment to a 16-step /s ?/ continuum that was embedded into two contexts: /mIst-mI?t/ in which /s-?/ are neutralized in AG and /ve'mIse/-/ve'mI?e/ in which they are not. The results from both experiments are indicative of a sound change in progress such that the neutralization is being undone under the influence of SG, but in such a way that there is a gradual shift between categories. The closer approximation of the groups on perception suggests that the sound change may be more advanced on this modality than in production. Overall, the findings are consistent with the idea that phonological contrasts are experience-based, i.e., a continuous function of the extent to which a subject is exposed to, and makes use of, the distinction and are thus compatible with exemplar models of speech. PMID- 25132829 TI - Contrasting group analysis of Brazilian students with dyslexia and good readers using the computerized reading and writing assessment battery "BALE". AB - The analysis of cognitive processes underpinning reading and writing skills may help to distinguish different reading ability profiles. The present study used a Brazilian reading and writing battery to compare performance of students with dyslexia with two individually matched control groups: one contrasting on reading competence but not age and the other group contrasting on age but not reading competence. Participants were 28 individuals with dyslexia (19 boys) with a mean age of 9.82 (SD +/- 1.44) drawn from public and private schools. These were matched to: (1) an age control group (AC) of 26 good readers with a mean age of 9.77 (SD +/- 1.44) matched by age, sex, years of schooling, and type of school; (2) reading control group (RC) of 28 younger controls with a mean age of 7.82 (SD +/- 1.06) matched by sex, type of school, and reading level. All groups were tested on four tasks from the Brazilian Reading and Writing Assessment battery ("BALE"): Written Sentence Comprehension Test (WSCT); Spoken Sentence Comprehension Test (OSCT); Picture-Print Writing Test (PPWT 1.1-Writing); and the Reading Competence Test (RCT). These tasks evaluate reading and listening comprehension for sentences, spelling, and reading isolated words and pseudowords (non-words). The dyslexia group scored lower and took longer to complete tasks than the AC group. Compared with the RC group, there were no differences in total scores on reading or oral comprehension tasks. However, dyslexics presented slower reading speeds, longer completion times, and lower scores on spelling tasks, even compared with younger controls. Analysis of types of errors on word and pseudoword reading items showed students with dyslexia scoring lower for pseudoword reading than the other two groups. These findings suggest that the dyslexics overall scores were similar to those of younger readers. However, specific phonological and visual decoding deficits showed that the two groups differ in terms of underpinning reading strategies. PMID- 25132827 TI - Toward a dual-learning systems model of speech category learning. AB - More than two decades of work in vision posits the existence of dual-learning systems of category learning. The reflective system uses working memory to develop and test rules for classifying in an explicit fashion, while the reflexive system operates by implicitly associating perception with actions that lead to reinforcement. Dual-learning systems models hypothesize that in learning natural categories, learners initially use the reflective system and, with practice, transfer control to the reflexive system. The role of reflective and reflexive systems in auditory category learning and more specifically in speech category learning has not been systematically examined. In this article, we describe a neurobiologically constrained dual-learning systems theoretical framework that is currently being developed in speech category learning and review recent applications of this framework. Using behavioral and computational modeling approaches, we provide evidence that speech category learning is predominantly mediated by the reflexive learning system. In one application, we explore the effects of normal aging on non-speech and speech category learning. Prominently, we find a large age-related deficit in speech learning. The computational modeling suggests that older adults are less likely to transition from simple, reflective, unidimensional rules to more complex, reflexive, multi dimensional rules. In a second application, we summarize a recent study examining auditory category learning in individuals with elevated depressive symptoms. We find a deficit in reflective-optimal and an enhancement in reflexive-optimal auditory category learning. Interestingly, individuals with elevated depressive symptoms also show an advantage in learning speech categories. We end with a brief summary and description of a number of future directions. PMID- 25132830 TI - Cognition-emotion interactions: patterns of change and implications for math problem solving. AB - Surprisingly little is known about whether relationships between cognitive and emotional states remain stable or change over time, or how different patterns of stability and/or change in the relationships affect problem solving abilities. Nevertheless, cross-sectional studies show that anxiety/worry may reduce working memory (WM) resources, and the ability to minimize the effects anxiety/worry is higher in individuals with greater WM capacity. To investigate the patterns of stability and/or change in cognition-emotion relations over time and their implications for problem solving, 126 14-year-olds' algebraic WM and worry levels were assessed twice in a single day before completing an algebraic math problem solving test. We used latent transition analysis to identify stability/change in cognition-emotion relations, which yielded a six subgroup solution. Subgroups varied in WM capacity, worry, and stability/change relationships. Among the subgroups, we identified a high WM/low worry subgroup that remained stable over time and a high WM/high worry, and a moderate WM/low worry subgroup that changed to low WM subgroups over time. Patterns of stability/change in subgroup membership predicted algebraic test results. The stable high WM/low worry subgroup performed best and the low WM capacity-high worry "unstable across time" subgroup performed worst. The findings highlight the importance of assessing variations in cognition-emotion relationships over time (rather than assessing cognition or emotion states alone) to account for differences in problem solving abilities. PMID- 25132831 TI - Medical management of hereditary optic neuropathies. AB - Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated. PMID- 25132832 TI - Biosphere frontiers of subsurface life in the sedimented hydrothermal system of Guaymas Basin. AB - Temperature is one of the key constraints on the spatial extent, physiological and phylogenetic diversity, and biogeochemical function of subsurface life. A model system to explore these interrelationships should offer a suitable range of geochemical regimes, carbon substrates and temperature gradients under which microbial life can generate energy and sustain itself. In this theory and hypothesis article, we make the case for the hydrothermally heated sediments of Guaymas Basin in the Gulf of California as a suitable model system where extensive temperature and geochemical gradients create distinct niches for active microbial populations in the hydrothermally influenced sedimentary subsurface that in turn intercept and process hydrothermally generated carbon sources. We synthesize the evidence for high-temperature microbial methane cycling and sulfate reduction at Guaymas Basin - with an eye on sulfate-dependent oxidation of abundant alkanes - and demonstrate the energetic feasibility of these latter types of deep subsurface life in previously drilled Guaymas Basin locations of Deep-Sea Drilling Project 64. PMID- 25132834 TI - Imposition of encapsulated non-indigenous probiotics into intestine may disturb human core microbiome. PMID- 25132833 TI - Aspergillus flavus infection induces transcriptional and physical changes in developing maize kernels. AB - Maize kernels are susceptible to infection by the opportunistic pathogen Aspergillus flavus. Infection results in reduction of grain quality and contamination of kernels with the highly carcinogenic mycotoxin, aflatoxin. To understanding host response to infection by the fungus, transcription of approximately 9000 maize genes were monitored during the host-pathogen interaction with a custom designed Affymetrix GeneChip(r) DNA array. More than 4000 maize genes were found differentially expressed at a FDR of 0.05. This included the up regulation of defense related genes and signaling pathways. Transcriptional changes also were observed in primary metabolism genes. Starch biosynthetic genes were down regulated during infection, while genes encoding maize hydrolytic enzymes, presumably involved in the degradation of host reserves, were up regulated. These data indicate that infection of the maize kernel by A. flavus induced metabolic changes in the kernel, including the production of a defense response, as well as a disruption in kernel development. PMID- 25132837 TI - A complex immunological idiotypic network for maintenance of tolerance. PMID- 25132835 TI - Insights into the Relationship between Toll Like Receptors and Gamma Delta T Cell Responses. AB - The tumor microenvironment is an important aspect of cancer biology that contributes to tumor initiation, tumor progression and responses to therapy. The composition and characteristics of the tumor microenvironment vary widely and are important in determining the anti-tumor immune response. Successful immunization requires activation of both innate and adaptive immunity. Generally, immune system is compromised in patients with cancer due to immune suppression, loss of tumor antigen expression and dysfunction of antigen presenting cells (APC). Thus, therapeutic immunization leading to cancer regression remains a significant challenge. Certain cells of the immune system, including dendritic cells (DCs) and gamma delta (gammadelta) T cells are capable of driving potent anti-tumor responses. The property of MHC-unrestricted cytotoxicity, high potential of cytokine release, tissue tropism and early activation in infections and malignant disease makes gammadelta T cells as an emerging candidate for immunotherapy. Various strategies are being developed to enhance anti-tumor immune responses of gammadelta T cells and DCs one of them is the use of novel adjuvants like toll like receptors (TLR) agonists, which enhance gammadelta T cell function directly or through DC activation, which has ability to prime gammadelta T cells. TLR agonists are being used clinically either alone or in combination with tumor antigens and has shown initial success in both enhancing immune responses and eliciting anti-tumor activity. TLR activated gammadelta T cells and DCs nurture each other's activation. This provides a potent base for first line of defense and manipulation of the adaptive response against pathogens and cancer. The available data provides a strong rationale for initiating combinatorial therapy for the treatment of diseases and this review will summarize the application of adjuvants (TLRs) for boosting immune response of gammadelta T cells to treat cancer and infectious diseases and their use in combinatorial therapy. PMID- 25132836 TI - Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation. AB - Pattern recognition receptors (PRRs) expressed on immune cells are crucial for the early detection of invading pathogens, in initiating early innate immune response and in orchestrating the adaptive immune response. PRRs are activated by specific pathogen-associated molecular patterns that are present in pathogenic microbes or nucleic acids of viruses or bacteria. However, inappropriate activation of these PRRs, such as the Toll-like receptors (TLRs), due to genetic lesions or chronic inflammation has been demonstrated to be a major cause of many hematological malignancies. Gain-of-function mutations in the TLR adaptor protein MYD88 found in 39% of the activated B cell type of diffuse large B cell lymphomas and almost 100% of Waldenstrom's macroglobulinemia further highlight the involvement of TLRs in these malignancies. MYD88 mutations result in the chronic activation of TLR signaling pathways, thus the constitutive activation of the transcription factor NFkappaB to promote cell survival and proliferation. These recent insights into TLR pathway driven malignancies warrant the need for a better understanding of TLRs in cancers and the development of novel anti-cancer therapies targeting TLRs. This review focuses on TLR function and signaling in normal or inflammatory conditions, and how mutations can hijack the TLR signaling pathways to give rise to cancer. Finally, we discuss how potential therapeutic agents could be used to restore normal responses to TLRs and have long lasting anti-tumor effects. PMID- 25132839 TI - Beyond grasses: the potential benefits of studying silicon accumulation in non grass species. PMID- 25132841 TI - Freedom in bioinformatics. PMID- 25132840 TI - Exploring the function of protein kinases in schistosomes: perspectives from the laboratory and from comparative genomics. AB - Eukaryotic protein kinases are well conserved through evolution. The genome of Schistosoma mansoni, which causes intestinal schistosomiasis, encodes over 250 putative protein kinases with all of the main eukaryotic groups represented. However, unraveling functional roles for these kinases is a considerable endeavor, particularly as protein kinases regulate multiple and sometimes overlapping cell and tissue functions in organisms. In this article, elucidating protein kinase signal transduction and function in schistosomes is considered from the perspective of the state-of-the-art methodologies used and comparative organismal biology, with a focus on current advances and future directions. Using the free-living nematode Caenorhabditis elegans as a comparator we predict roles for various schistosome protein kinases in processes vital for host invasion and successful parasitism such as sensory behavior, growth and development. It is anticipated that the characterization of schistosome protein kinases in the context of parasite function will catalyze cutting edge research into host parasite interactions and will reveal new targets for developing drug interventions against human schistosomiasis. PMID- 25132842 TI - Repair and regeneration properties of Ginkgo biloba after ischemic brain injury. PMID- 25132843 TI - Automatic labeling of vertebral levels using a robust template-based approach. AB - Context. MRI of the spinal cord provides a variety of biomarkers sensitive to white matter integrity and neuronal function. Current processing methods are based on manual labeling of vertebral levels, which is time consuming and prone to user bias. Although several methods for automatic labeling have been published; they are not robust towards image contrast or towards susceptibility related artifacts. Methods. Intervertebral disks are detected from the 3D analysis of the intensity profile along the spine. The robustness of the disk detection is improved by using a template of vertebral distance, which was generated from a training dataset. The developed method has been validated using T1- and T2-weighted contrasts in ten healthy subjects and one patient with spinal cord injury. Results. Accuracy of vertebral labeling was 100%. Mean absolute error was 2.1 +/- 1.7 mm for T2-weighted images and 2.3 +/- 1.6 mm for T1 weighted images. The vertebrae of the spinal cord injured patient were correctly labeled, despite the presence of artifacts caused by metallic implants. Discussion. We proposed a template-based method for robust labeling of vertebral levels along the whole spinal cord for T1- and T2-weighted contrasts. The method is freely available as part of the spinal cord toolbox. PMID- 25132844 TI - Nonreference medical image edge map measure. AB - Edge detection is a key step in medical image processing. It is widely used to extract features, perform segmentation, and further assist in diagnosis. A poor quality edge map can result in false alarms and misses in cancer detection algorithms. Therefore, it is necessary to have a reliable edge measure to assist in selecting the optimal edge map. Existing reference based edge measures require a ground truth edge map to evaluate the similarity between the generated edge map and the ground truth. However, the ground truth images are not available for medical images. Therefore, a nonreference edge measure is ideal for medical image processing applications. In this paper, a nonreference reconstruction based edge map evaluation (NREM) is proposed. The theoretical basis is that a good edge map keeps the structure and details of the original image thus would yield a good reconstructed image. The NREM is based on comparing the similarity between the reconstructed image with the original image using this concept. The edge measure is used for selecting the optimal edge detection algorithm and optimal parameters for the algorithm. Experimental results show that the quantitative evaluations given by the edge measure have good correlations with human visual analysis. PMID- 25132838 TI - Leaf development: a cellular perspective. AB - Through its photosynthetic capacity the leaf provides the basis for growth of the whole plant. In order to improve crops for higher productivity and resistance for future climate scenarios, it is important to obtain a mechanistic understanding of leaf growth and development and the effect of genetic and environmental factors on the process. Cells are both the basic building blocks of the leaf and the regulatory units that integrate genetic and environmental information into the developmental program. Therefore, to fundamentally understand leaf development, one needs to be able to reconstruct the developmental pathway of individual cells (and their progeny) from the stem cell niche to their final position in the mature leaf. To build the basis for such understanding, we review current knowledge on the spatial and temporal regulation mechanisms operating on cells, contributing to the formation of a leaf. We focus on the molecular networks that control exit from stem cell fate, leaf initiation, polarity, cytoplasmic growth, cell division, endoreduplication, transition between division and expansion, expansion and differentiation and their regulation by intercellular signaling molecules, including plant hormones, sugars, peptides, proteins, and microRNAs. We discuss to what extent the knowledge available in the literature is suitable to be applied in systems biology approaches to model the process of leaf growth, in order to better understand and predict leaf growth starting with the model species Arabidopsis thaliana. PMID- 25132845 TI - Neural networks and fault probability evaluation for diagnosis issues. AB - This paper presents a new FDI technique for fault detection and isolation in unknown nonlinear systems. The objective of the research is to construct and analyze residuals by means of artificial intelligence and probabilistic methods. Artificial neural networks are first used for modeling issues. Neural networks models are designed for learning the fault-free and the faulty behaviors of the considered systems. Once the residuals generated, an evaluation using probabilistic criteria is applied to them to determine what is the most likely fault among a set of candidate faults. The study also includes a comparison between the contributions of these tools and their limitations, particularly through the establishment of quantitative indicators to assess their performance. According to the computation of a confidence factor, the proposed method is suitable to evaluate the reliability of the FDI decision. The approach is applied to detect and isolate 19 fault candidates in the DAMADICS benchmark. The results obtained with the proposed scheme are compared with the results obtained according to a usual thresholding method. PMID- 25132847 TI - The incidence and risk factors for lower limb skin graft failure. AB - Lower limb skin grafts are thought to have higher failure rates than skin grafts in other sites of the body. Currently, there is a paucity of literature on specific factors associated with lower limb skin graft failure. We present a series of 70 lower limb skin grafts in 50 patients with outcomes at 6 weeks. One third of lower limb skin grafts went on to fail with increased BMI, peripheral vascular disease, and immunosuppressant medication use identified as significant risk factors. PMID- 25132846 TI - Cosmetic contact sensitivity in patients with melasma: results of a pilot study. AB - Background. Some of the patients with melasma perhaps have pigmented cosmetic dermatitis. However, cosmetic contact sensitivity in melasma remains poorly studied particularly in the Indian context. Objectives. To study cosmetic contact sensitivity in patients with melasma. Materials and Methods. 67 (F : M = 55 : 12) consecutive patients with melasma between 19 and 49 years of age were patch tested sequentially during January-December, 2012, with Indian Cosmetic and Fragrance Series, Indian Sunscreen Series, p-phenylenediamine, and patient's own cosmetic products. Results. 52 (78%) patients were in the age group of 20-40 years. The duration of melasma varied from 1 month to 20 years. Centrofacial, malar, and mandibular patterns were observed in 48 (72%), 18 (27%), and 1 (1%) patients, respectively. Indian Cosmetics and Fragrance Series elicited positive reactions in 29 (43.3%) patients. Cetrimide was the most common contact sensitizers eliciting positivity in 15 (52%) patients, followed by gallate mix in 9 (31%) patients and thiomersal in 7 (24%) patients. Only 2 of the 42 patients showed positive reaction from their own cosmetics while the other 5 patients had irritant reaction. Indian Sunscreen Series did not elicit any positive reaction. Conclusion. Cosmetics contact sensitivity appears as an important cause of melasma not associated with pregnancy, lactation, or hormone therapy. PMID- 25132848 TI - Online medicine for pregnant women. AB - Objective. To assess the use of cell phones and email as means of communication between pregnant women and their gynecologists and family physicians. Study Design. A cross-sectional study of pregnant women at routine followup. One hundred and twenty women participated in the study. Results. The mean age was 27.4 +/- 3.4 years. One hundred nineteen women owned a cell phone and 114 (95%) had an email address. Seventy-two women (60%) had their gynecologist's cell phone number and 50 women (42%) had their family physician's cell phone number. More women contacted their gynecologist via cell phone or email during pregnancy compared to their family physician (P = 0.005 and 0.009, resp.). Most preferred to communicate with their physician via cell phone at predetermined times, but by email at any time during the day (P < 0.0001). They would use cell phones for emergencies or unusual problems but preferred email for other matters (P < 0.0001). Conclusions. Pregnant women in the Negev region do not have a preference between the use of cell phones or email for medical consultation with their gynecologist or family physician. The provision of the physician's cell phone numbers or email address together with the provision of guidelines and resources could improve healthcare services. PMID- 25132849 TI - IN-MACA-MCC: Integrated Multiple Attractor Cellular Automata with Modified Clonal Classifier for Human Protein Coding and Promoter Prediction. AB - Protein coding and promoter region predictions are very important challenges of bioinformatics (Attwood and Teresa, 2000). The identification of these regions plays a crucial role in understanding the genes. Many novel computational and mathematical methods are introduced as well as existing methods that are getting refined for predicting both of the regions separately; still there is a scope for improvement. We propose a classifier that is built with MACA (multiple attractor cellular automata) and MCC (modified clonal classifier) to predict both regions with a single classifier. The proposed classifier is trained and tested with Fickett and Tung (1992) datasets for protein coding region prediction for DNA sequences of lengths 54, 108, and 162. This classifier is trained and tested with MMCRI datasets for protein coding region prediction for DNA sequences of lengths 252 and 354. The proposed classifier is trained and tested with promoter sequences from DBTSS (Yamashita et al., 2006) dataset and nonpromoters from EID (Saxonov et al., 2000) and UTRdb (Pesole et al., 2002) datasets. The proposed model can predict both regions with an average accuracy of 90.5% for promoter and 89.6% for protein coding region predictions. The specificity and sensitivity values of promoter and protein coding region predictions are 0.89 and 0.92, respectively. PMID- 25132850 TI - Analysis and Determination of Trace Metals (Nickel, Cadmium, Chromium, and Lead) in Tissues of Pampus argenteus and Platycephalus indicus in the Hara Reserve, Iran. AB - The accumulations of Cd, Ni, Pb, and Cr were measured in muscle, gill, kidney, and liver of Platycephalus indicus and Pampus argenteus. Our results indicated that all metals were found to be the highest in tissues in P. indicus (benthic species). Except Ni in P. indicus, concentrations of metals and bioaccumulation factor were in the following sequence: liver > kidney > gill > muscle. The data revealed that there is a significant negative correlation between concentrations of metals and size and age factors. The Ni and Cr levels in the muscles were higher than the maximum acceptable limit recommended by WHO and FEPA. Similarly, the concentration of Pb measured in P. indicus muscle exceeded the FAO standard limit. PMID- 25132851 TI - Laparoscopic adrenalectomy for adrenal tumors. AB - Objective. To evaluate the indication and the clinical value of laparoscopic adrenalectomy of different types of adrenal tumor. Methods. From 2009 to 2014, a total of 110 patients were diagnosed with adrenal benign tumor by CT scan and we performed laparoscopic adrenalectomy. The laparoscopic approach has been the procedure of choice for surgery of benign adrenal tumors, and the upper limit of tumor size was thought to be 6 cm. Results. 109 of 110 cases were successful; only one was converted to open surgery due to bleeding. The average operating time and intraoperative blood loss of pheochromocytoma were significantly more than the benign tumors (P < 0.05). After 3 months of follow-up, the preoperative symptoms were relieved and there was no recurrence. Conclusions. Laparoscopic adrenalectomy has the advantages of minimal invasion, less blood loss, fewer complications, quicker recovery, and shorter hospital stay. The full preparation before operation can decrease the average operating time and intraoperative blood loss of pheochromocytomas. Laparoscopic adrenalectomy should be considered as the first choice treatment for the resection of adrenal benign tumor. PMID- 25132852 TI - MTNR1B Genetic Variability Is Associated with Gestational Diabetes in Czech Women. AB - The gene MTNR1B encodes a receptor for melatonin. Melatonin receptors are expressed in human beta-cells, which implies that genetic variants might affect glucose tolerance. Meta-analysis confirmed that the rs10830963 shows the most robust association. The aim of the study was to assess the rs10830963 in Czech GDM patients and controls and to study relations between the SNP and biochemical as well as anthropometric characteristics. Our cohort consisted of 880 women; 458 were diagnosed with GDM, and 422 were normoglycemic controls without history of GDM. Despite similar BMI, the GDM group showed higher WHR, waist circumference, abdominal circumference, and total body fat content. The risk allele G was more frequent in the GDM group (38.3 versus 29.4% in controls, OR 1.49 CI95% [1.22; 1.82]; P OR = 0.0001). In spite of higher frequency, the G allele in the GDM group was not associated with any markers of glucose metabolism. In contrast, controls showed significant association of the allele G with FPG and with postchallenge glycemia during the oGTT. Frequency analysis indicates that rs10830963 is involved in gestational diabetes in Czech women. However, the association of the SNP with glucose metabolism, which is obvious in controls, is covert in women who have experienced GDM. PMID- 25132853 TI - FBP1 Is an Interacting Partner of Menin. AB - Multiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by tumors in multiple endocrine tissues such as the parathyroid glands, the pituitary gland, and the enteropancreatic neuroendocrine tissues. MEN1 is usually caused by mutations in the MEN1 gene that codes for the protein menin. Menin interacts with proteins that regulate transcription, DNA repair and processing, and maintenance of cytoskeletal structure. We describe the identification of FBP1 as an interacting partner of menin in a large-scale pull-down assay that also immunoprecipitated RBBP5, ASH2, and LEDGF, which are members of complex proteins associated with SET1 (COMPASS), a protein complex that methylates histone H3. This interaction was confirmed by coimmunoprecipitation and Flag-pull-down assays. Furthermore, menin localized to the FUSE site on the MYC promoter, a site that is transactivated by FBP1. This investigation therefore places menin in a pathway that regulates MYC gene expression and has important implications for the biological function of menin. PMID- 25132854 TI - Fasting hyperglycemia increases in-hospital mortality risk in nondiabetic female patients with acute myocardial infarction: a retrospective study. AB - Previous studies had shown that elevated admission plasma glucose (APG) could increase mortality rate and serious complications of acute myocardial infarction (AMI), but whether fasting plasma glucose (FPG) had the same role remains controversial. In this retrospective study, 253 cases of AMI patients were divided into diabetic (n = 87) and nondiabetic group (n = 166). Our results showed that: compared with the nondiabetic patients, diabetic patients had higher APG, FPG, higher plasma triglyceride, higher rates of painless AMI (P < 0.01), non-ST-segment elevation myocardial infarction (NSTEMI), and reinfraction (P < 0.05). They also had lower high density lipoprotein cholesterol and rate of malignant arrhythmia, but in-hospital mortality rate did not differ significantly (P > 0.05). While nondiabetic patients were subgrouped in terms of APG and FPG (cut points were 11.1 mmol/L and 7.0 mmol/L, resp.), the mortality rate had significant difference (P < 0.01), whereas glucose level lost significance in diabetic group. Multivariate logistic regression analysis showed that FPG (OR: 2.014; 95% confidence interval: 1.296-3.131; p < 0.01) but not APG was independent predictor of in-hospital mortality for nondiabetic patients. These results indicate that FPG can be an independent predictor for mortality in nondiabetic female patients with AMI. PMID- 25132855 TI - Radiological assessment of the Indian children with congenital sensorineural hearing loss. AB - Introduction. Congenital sensorineural hearing loss is one of the most common birth defects with incidence of approximately 1 : 1000 live births. Imaging of cases of congenital sensorineural hearing loss is frequently performed in an attempt to determine the underlying pathology. There is a paucity of literature from India and for this reason we decided to conduct this study in Indian context to evaluate the various cochleovestibular bony and nerve anomalies by HRCT scan of temporal bone and MRI with 3D scan of inner ear in a tertiary care centre. Material and Methods. A total of 280 children with congenital deafness (158 males and 122 females), between January 2002 to June 2013 were included in the study and they were assessed radiologically by HRCT scan of temporal bone and MRI with 3D scan of inner ear. Results. In the present study we found various congenital anomalies of bony labyrinth and vestibulocochlear nerve. Out of 560 inner ears we found 78 anomalous inner ears. Out of these 78 inner ears 57 (73%) had cochlear anomaly, 68 (87.1%) had anomalous vestibule, 44 (56.4%) had abnormal vestibular aqueduct, 24 (30.7%) had anomalous IAC, and 23 (29.4%) had abnormal cochleovestibular nerves. Conclusion. In present study, we found lower incidences of congenital anomalies comparative to existing literature. PMID- 25132857 TI - The Secretome of Bone Marrow and Wharton Jelly Derived Mesenchymal Stem Cells Induces Differentiation and Neurite Outgrowth in SH-SY5Y Cells. AB - The goal of this study was to determine and compare the effects of the secretome of mesenchymal stem cells (MSCs) isolated from human bone-marrow (BMSCs) and the Wharton jelly surrounding the vein and arteries of the umbilical cord (human umbilical cord perivascular cells (HUCPVCs)) on the survival and differentiation of a human neuroblastoma cell line (SH-SY5Y). For this purpose, SH-SY5Y cells were differentiated with conditioned media (CM) from the MSCs populations referred above. Retinoic acid cultured cells were used as control for neuronal differentiated SH-SY5Y cells. SH-SY5Y cells viability assessment revealed that the secretome of BMSCs and HUCPVCs, in the form of CM, was able to induce their survival. Moreover, immunocytochemical experiments showed that CM from both MSCs was capable of inducing neuronal differentiation of SH-SY5Y cells. Finally, neurite lengths assessment and quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis demonstrated that CM from BMSCs and HUCPVCs differently induced neurite outgrowth and mRNA levels of neuronal markers exhibited by SH-SY5Y cells. Overall, our results show that the secretome of both BMSCs and HUCPVCs was capable of supporting SH-SY5Y cells survival and promoting their differentiation towards a neuronal phenotype. PMID- 25132858 TI - Wrist-ankle acupuncture for the treatment of pain symptoms: a systematic review and meta-analysis. AB - Routine acupuncture incorporates wrist-ankle acupuncture (WAA) for its analgesic effect, but WAA is not widely used in clinics due to incomplete knowledge of its effectiveness and concerns about less clinical research and because less people know it. This study aimed to assess the efficacy and possible adverse effects of WAA or WAA adjuvants in the treatment of pain symptoms. This study compared WAA or WAA adjuvant with the following therapies: western medication (WM), sham acupuncture (SA), or body acupuncture (BA). Randomized controlled trials (RCTs) were searched systematically in related electronic databases by two independent reviewers. 33 RCTs were finally included, in which 7 RCTs were selected for meta analysis. It was found that WAA or WAA adjuvant was significantly more effective than WM, SA, or BA in pain relief. There was nothing different between WAA and SA in adverse events, but WAA was marginally significantly safer than WM. Although both WAA and WAA adjuvant appeared to be more effective than WM, SA, or BA in the treatment of pain symptoms with few side effects, further studies with better and more rigorously designed are still necessary to ensure the efficacy and safety issue of WAA due to the poor methodology and small sample size of previous studies. PMID- 25132856 TI - Management of fibrosis: the mesenchymal stromal cells breakthrough. AB - Fibrosis is the endpoint of many chronic inflammatory diseases and is defined by an abnormal accumulation of extracellular matrix components. Despite its slow progression, it leads to organ malfunction. Fibrosis can affect almost any tissue. Due to its high frequency, in particular in the heart, lungs, liver, and kidneys, many studies have been conducted to find satisfactory treatments. Despite these efforts, current fibrosis management therapies either are insufficiently effective or induce severe adverse effects. In the light of these facts, innovative experimental therapies are being investigated. Among these, cell therapy is regarded as one of the best candidates. In particular, mesenchymal stromal cells (MSCs) have great potential in the treatment of inflammatory diseases. The value of their immunomodulatory effects and their ability to act on profibrotic factors such as oxidative stress, hypoxia, and the transforming growth factor-beta1 pathway has already been highlighted in preclinical and clinical studies. Furthermore, their propensity to act depending on the microenvironment surrounding them enhances their curative properties. In this paper, we review a large range of studies addressing the use of MSCs in the treatment of fibrotic diseases. The results reported here suggest that MSCs have antifibrotic potential for several organs. PMID- 25132859 TI - Syndrome Differentiation of Diabetes by the Traditional Chinese Medicine according to Evidence-Based Medicine and Expert Consensus Opinion. AB - In Chinese medicine, diabetes belongs to the category of "Xiaoke disease (disease with symptoms of frequent drinking and urination)"; in the traditional sense, its pathogenesis is "Yin deficiency and dryness-heat." However, over time, changes in the social environment and lifestyle have also changed the use of traditional Chinese medicine (TCM) in diabetes. In this study, we performed diabetes syndrome differentiation using TCM according to evidence-based medicine and expert consensus opinion. PMID- 25132860 TI - IKK beta -Targeted Anti-Inflammatory Activities of a Butanol Fraction of Artificially Cultivated Cordyceps pruinosa Fruit Bodies. AB - The inhibitory activities of the Cordyceps pruinosa butanol fraction (Cp-BF) were investigated by determining inflammatory responses of lipopolysaccharide (LPS) treated RAW264.7 macrophage cells and by evaluating HCl/ethanol (EtOH)-triggered gastric ulcers in mice. The molecular mechanisms of the inhibitory effects of Cp BF were investigated by identifying target enzymes using biochemical and molecular biological approaches. Cp-BF strongly inhibited the production of NO and TNF-alpha, release of reactive oxygen species (ROS), phagocytic uptake of FITC-dextran, and mRNA expression levels of interleukin (IL)-6, inducible NO synthase (iNOS), and tumour necrosis factor-alpha (TNF)-alpha in activated RAW264.7 cells. Cp-BF also strongly downregulated the NF-kappaB pathway by suppressing IKKbeta according to luciferase reporter assays and immunoblot analysis. Furthermore, Cp-BF blocked both increased levels of NF-kappaB-mediated luciferase activities and phosphorylation of p65/p50 observed by IKKbeta overexpression. Finally, orally administered Cp-BF was found to attenuate gastric ulcer and block the phosphorylation of IkappaBalpha induced by HCl/EtOH. Therefore, these results suggest that the anti-inflammatory activity of Cp-BF may be mediated by suppression of IKKalpha and its downstream NF-kappaB activation. Since our group has established the mass cultivation conditions by developing culture conditions for Cordyceps pruinosa, the information presented in this study may be useful for developing new anti-inflammatory agents. PMID- 25132861 TI - Effect of ST36 Acupuncture on Hyperventilation-Induced CO 2 Reactivity of the Basilar and Middle Cerebral Arteries and Heart Rate Variability in Normal Subjects. AB - This study was conducted to verify the effect of acupuncture on cerebral haemodynamics to provide evidence for the use of acupuncture treatment as a complementary therapy for the high-risk stroke population. The effect of ST36 acupuncture treatment on the hyperventilation-induced CO2 reactivity of the basilar and middle cerebral arteries was studied in 10 healthy male volunteers (mean age, 25.2 +/- 1.5 years) using a transcranial Doppler sonography with an interval of 1 week between measurements, and a portable ECG monitoring system was used to obtain ECG data simultaneously. The CO2 reactivity of the basilar and middle cerebral arteries increased significantly after ST36 acupuncture treatment, whereas the mean arterial blood pressure and pulse rate did not change significantly. The high-frequency power significantly increased after ST36 acupuncture treatment, and the percentage increase of high-frequency power correlated significantly with the percentage increase in the CO2 reactivity of the contralateral middle cerebral artery. These data suggest that ST36 acupuncture treatment increases CO2 reactivity, indicating improvement of vasodilatory potential of the cerebral vasculature to compensate for fluctuations caused by changes in external conditions. The increase in parasympathetic tone by ST36 acupuncture treatment is responsible for this therapeutic effect. PMID- 25132863 TI - A note regarding problems with interaction and varying block sizes in a comparison of endotracheal tubes. AB - A randomized clinical experiment to compare two types of endotracheal tubes utilized a block design where each of the six participating anesthesiologists performed tube insertions for an equal number of patients for each type of tube. Five anesthesiologists intubated at least three patients with each tube type, but one anesthesiologist intubated only one patient per tube type. Overall, one type of tube outperformed the other on all three effectiveness measures. However, analysis of the data using an interaction model gave conflicting and misleading results, making the tube with the better performance appear to perform worse. This surprising result was caused by the undue influence of the data for the anesthesiologist who intubated only two patients. We therefore urge caution in interpreting results from interaction models with designs containing small blocks. PMID- 25132864 TI - A necessary evil? Intra-abdominal hypertension complicating burn patient resuscitation. AB - OBJECTIVE: Severe burns are devastating injuries that result in considerable systemic inflammation and often require resuscitation with large volumes of fluid. The result of massive resuscitation is often raised intra-abdominal pressures leading to Intra-abdominal hypertension (IAH) and the secondary abdominal compartment syndrome. The objective of this study is to conduct (1) a 10 year retrospective study to investigate epidemiological factors contributing to burn injuries in Alberta, (2) to characterize fluid management and incidence of IAH and ACS and (3) to review fluid resuscitation with a goal to identify optimal strategies for fluid resuscitation. DESIGN: A comprehensive 10-year retrospective review of burn injuries from 1999. OUTCOME MEASURES: Age, sex, date, mechanism of injury, location of incident, on scene vitals and GCS, type of transport to hospital and routing, ISS, presenting vitals and GCS, diagnoses, procedures, complications, hospital LOS, ICU LOS, and events surrounding the injury. RESULTS: One hundred and seventy five patients (79.4% M, 20.6% F) were identified as having traumatic burn injuries with a mean ISS score of 21.8 (+/ 8.3). The mean age was 41.6 (+/-17.5) (range 14-94) years. Nearly half (49.7%) of patients suffered their injuries at home, 17.7% were related to industrial incidents and 14.3% were MVC related. One hundred and ten patients required ICU admission. ICU LOS 18.5 (+/-8.8) days. Hospital LOS 38.0 (+/-37.8) days. The mean extent of burn injury was 31.4 (+/-20.9) % TBSA. Nearly half of the patients suffered inhalational injuries (mild 12.5%, moderate 13.7%, severe 9.1%). Thirty nine (22.2%) of patients died from their injuries. Routine IAP monitoring began in September, 2005 with 15 of 28 patients having at least two IAP measurements. The mean IAP was 16.5 (+/-5.7) cm H2O (range: 1-40) with an average of 58 (+/-97) IAP measurements per patient. Those patients with IAP monitoring had an average TBSA of 35.0 (+/-16.0)%, ISS of 47.5 (+/-7.5). The mean 48 hr fluid balance was 25.6 (+/-11.1)L exceeding predicted Parkland formula estimates by 86 (+/-32)%. CONCLUSIONS: Further evaluation of IAP monitoring is needed to further characterize IAP and fluid resuscitation in patients with burn injuries. PMID- 25132865 TI - Heat Stress Increases Long-term Human Migration in Rural Pakistan. AB - Human migration attributable to climate events has recently received significant attention from the academic and policy communities (1-2). Quantitative evidence on the relationship between individual, permanent migration and natural disasters is limited (3-9). A 21-year longitudinal survey conducted in rural Pakistan (1991 2012) provides a unique opportunity to understand the relationship between weather and long-term migration. We link individual-level information from this survey to satellite-derived measures of climate variability and control for potential confounders using a multivariate approach. We find that flooding-a climate shock associated with large relief efforts-has modest to insignificant impacts on migration. Heat stress, however-which has attracted relatively little relief-consistently increases the long-term migration of men, driven by a negative effect on farm and non-farm income. Addressing weather-related displacement will require policies that both enhance resilience to climate shocks and lower barriers to welfare-enhancing population movements. PMID- 25132866 TI - Treatment of Crohn's disease complicated with myelodysplastic syndrome via allogeneic hematopoietic stem cell transplantation: case report and literature review. AB - Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract arising in individuals with genetic predisposing factors and abnormalities of the immune system. Myelodysplastic syndrome (MDS), an acquired clonal hematologic disorder, is characterized by peripheral blood cytopenia, dysplastic changes in several types of hematopoietic cells of the bone marrow and peripheral blood, and a high risk of transformation to acute leukemia. CD rarely occurs in combination with MDS, and MDS treatment with hematopoietic stem cell transplantation (HSCT) has not been frequently reported. We report the case of a 50-year-old Chinese male who presented with abdominal pain, diarrhea, and fatigue. CD was diagnosed by colonoscopy, imaging studies, and pathological examination. He was initially treated with mesalazine and prednisone and thereafter he presented with pancytopenia. MDS (RAEB-I) was diagnosed by bone marrow examination, and karyotyping revealed 47, XY, +8. The patient was treated with thalidomide, andriol, and decitabine. Allogeneic HSCT was performed with a human leukocyte antigen-matched sibling as the donor. The patient is currently well at 14 months after HSCT, without abdominal pain, diarrhea, or fatigue. HSCT may be a promising treatment option for patients with combined CD and MDS. PMID- 25132868 TI - Basic aspects of the pharmacodynamics of tolperisone, a widely applicable centrally acting muscle relaxant. AB - Tolperisone (2-methyl-1-(4-methylphenyl)-3-piperidin-1-ylpropan-1-one hydro chloride) was introduced in the clinical practice more than forty years ago and is still evaluated as a widely applicable compound in pathologically elevated skeletal muscle tone (spasticity) and related pains of different origin. In the present review, basic pharmacodynamic effects measured on whole animals, analyses of its actions on cell and tissue preparations and molecular mechanism of action on sodium and calcium channels are summarized as recently significantly new data were reported. PMID- 25132867 TI - Successful natural interferon-beta plus ribavirin therapy in a chronic hepatitis C patient after discontinuation of interferon-alpha treatment due to arrhythmia and interstitial pneumonia. AB - A 71-year-old female patient with hepatitis C virus genotype 1 had previously discontinued interferon (IFN)-alpha plus ribavirin therapy, pegylated IFN-alpha (pegIFN-alpha) monotherapy, and natural IFN-alpha monotherapy because of arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. She subsequently completed 72 weeks of natural IFN-beta plus ribavirin therapy without remarkable adverse effects and achieved a sustained viral response, suggesting differences in the pharmacological properties and biological effects of IFN-alpha and IFN-beta. Thus, natural IFN-beta plus ribavirin therapy may be a treatment option for patients with poor tolerance to IFN-alpha or pegIFN-alpha treatments. PMID- 25132862 TI - Challenges associated with Penetration of Nanoparticles across Cell and Tissue Barriers: A Review of Current Status and Future Prospects. AB - Nanoparticles (NPs) have emerged as an effective modality for the treatment of various diseases including cancer, cardiovascular and inflammatory diseases. Various forms of NPs including liposomes, polymer particles, micelles, dendrimers, quantum dots, gold NPs and carbon nanotubes have been synthesized and tested for therapeutic applications. One of the greatest challenges that limit the success of NPs is their ability to reach the therapeutic site at necessary doses while minimizing accumulation at undesired sites. The biodistribution of NPs is determined by body's biological barriers that manifest in several distinct ways. For intravascular delivery of NPs, the barrier manifests in the form of: (i) immune clearance in the liver and spleen, (ii) permeation across the endothelium into target tissues, (iii) penetration through the tissue interstitium, (iv) endocytosis in target cells, (v) diffusion through cytoplasm and (vi) eventually entry into the nucleus, if required. Certain applications of NPs also rely on delivery through alternate routes including skin and mucosal membranes of the nose, lungs, intestine and vagina. In these cases, the diffusive resistance of these tissues poses a significant barrier to delivery. This review focuses on the current understanding of penetration of NPs through biological barriers. Emphasis is placed on transport barriers and not immunological barriers. The review also discusses design strategies for overcoming the barrier properties. PMID- 25132869 TI - Contribution of neuraminidase of influenza viruses to the sensitivity to sera inhibitors and reassortment efficiency. AB - Live attenuated influenza vaccine (LAIV) represent reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments inherited from circulating wild-type (WT) parental influenza viruses recommended for inclusion into seasonal vaccine formulation, and the 6 internal protein-encoding gene segments from cold-adapted attenuated master donor viruses (genome composition 6:2). In this study, we describe the obstacles in developing LAIV strains while taking into account the phenotypic peculiarities of WT viruses used for reassortment. Genomic composition analysis of 849 seasonal LAIV reassortants revealed that over 80% of reassortants based on inhibitor-resistant WT viruses inherited WT NA, compared to 26% of LAIV reassortants based on inhibitor sensitive WT viruses. In addition, the highest percentage of LAIV genotype reassortants was achieved when WT parental viruses were resistant to non-specific serum inhibitors. We demonstrate that NA may play a role in influenza virus sensitivity to non-specific serum inhibitors. Replacing NA of inhibitor-sensitive WT virus with the NA of inhibitor-resistant master donor virus significantly decreased the sensitivity of the resulting reassortant virus to serum heat-stable inhibitors. PMID- 25132870 TI - Respiratory Syncytial Virus Infection in High-risk Infants - an Update on Palivizumab Prophylaxis. AB - Morbidity due to respiratory syncytial virus (RSV) disease is still high in infants and children worldwide during the first two to five years of life. Certain categories of high-risk infants with increased morbidity and mortality attributed to RSV disease have been identified and are included in national recommendations for prophylaxis with the monoclonal RSV antibody palivizumab. Most guidelines recommend palivizumab for preterm infants born less than or equal to 32 weeks gestational age with or without bronchopulmonary dysplasia, those born between 33 and 35 weeks gestational age with additional risk factors, and infants and children with hemodynamically significant congenital heart disease. Over the last years several rare diseases have been identified demonstrating high morbidity associated with RSV disease, thus, extension of guidelines for the prophylaxis with palivizumab for these patients with rare diseases including children with malignancy, congenital and acquired immune deficiency, Down syndrome, neuromuscular impairment, cystic fibrosis, congenital diaphragmatic hernia and other severe respiratory disease is increasingly discussed. Efficacy of palivizumab prophylaxis is documented by meta-analysis, and different economic analyses demonstrate cost-effectiveness of palivizumab for the most common indications during the first RSV season. PMID- 25132871 TI - Classification of distal radius physeal fractures not included in the salter harris system. AB - INTRODUCTION: The most commonly used classification for pediatric physeal fractures has been proposed by Salter and Harris. Among the most suitable classification schemes are those proposed by Ogden and Peterson who added several new types of injuries. The purpose of this study was to examine the value of both schemes to classify all different types of physeal injuries of the distal radius that are not included in the Salter-Harris system and to test a new nomenclature to classify and guide treatment for the whole spectrum of these injuries. METHODS: A total of 292 children who were admitted for a physeal fracture of the distal radius that could not be classified according to the Salter-Harris system were identified from the hospital database. All radiographs were carefully examined and classified according to the existing classifications of Ogden and Peterson and a modified classification scheme. The results of the treatment were also evaluated. RESULTS: Ninety-six physeal injuries could not be classified using the classification schemes of Ogden and Peterson. All injuries could be classified in five types using the new, modified nomenclature. Growth abnormalities of the distal radius were evaluated after an average follow-up time of 11 years. Growth arrest due to a physeal bar was detected only in one patient. DISCUSSION: The proposed modified scheme is practical, incorporates all previous classification systems, allows classification of all physeal injuries of the distal radius that are not included in the Salter-Harris system and may assist comparison of treatment outcomes. PMID- 25132872 TI - Tranexamic Acid Reduces Blood Loss and Transfusion in Patients Undergoing Total Knee Arthroplasty without Tourniquet: A Prospective Randomized Controlled Trial. AB - INTRODUCTION: Blood loss during and after total knee arthroplasty (TKA) can lead to substantial morbidity and the need for blood transfusions. There are several methods to minimize blood loss and to decrease transfusion rates in patients undergoing TKA. Tranexamic acid is an antifibrinolytic agent with known efficacy for achieving these goals. Currently, many surgeons are performing TKA without the use of tourniquet. Consequently, the aim of the study is to evaluate whether tranexamic acid reduces blood loss during and after TKA without the adjunctive use of above-the-knee tourniquet. METHODS: We performed a prospective randomized controlled trial (1:1 fashion) on the use of tranexamic acid versus placebo in 50 patients undergoing TKA (without tourniquet). The treatment group received two (preoperative and postoperative) 15 mg/kg doses. The primary endpoint was blood transfusion rate. We collected data about demographic and procedural characteristics, hemoglobin and hematocrit values, drain blood loss at 24 hours as well as adverse events. RESULTS: There were no transfusions in the treatment group, whereas 32% of the control group required transfusion (p<0.01). The treatment group had higher hematocrit and hemoglobin levels at 24, 48 and 72 hours after surgery (all p<0.01) and lower drain loss at 24hours (363.4+/-141 vs 626+/-260ml, p=<0,001). There were no in-hospital or six-month thromboembolic complications. DISCUSSION: A double-dose of tranexamic acid was safe and effective, reducing blood loss and preventing the need of blood transfusion in patients undergoing TKA without above-the-need tourniquet. PMID- 25132873 TI - Social Variations in Perceived Parenting Styles among Norwegian Adolescents. AB - Previous research has documented the associations between parenting and parenting styles and child and adolescent outcomes. Little is known, however, about the social structuring of parenting in contemporary Nordic welfare states. A possible hypothesis is that socioeconomic variations in parenting styles in present-day Norway will be small because of material affluence, limited income inequality, and an active welfare state. This study examines social variations in parenting as perceived by Norwegian adolescents (N = 1362), with a focus on four parenting style dimensions: responsiveness, demandingness, neglecting, and intrusive. Responsiveness seems to capture major divisions in parenting. Adolescents in families with fewer economic resources experienced their parents as somewhat less responsive, but responsiveness was not related to parents' education. Low parental education was on the other hand associated with perceptions of parents as neglecting and intrusive. Viewing parents as demanding did neither vary with parental education nor with family economy. Substantial variations in parenting styles persist in present-day Norway, and these variations correspond moderately with the families' placement in the social structure. Indicators of parenting and parenting styles may be useful indicators of some aspects of child and adolescent well-being. PMID- 25132874 TI - Medication adherence and community pharmacy: a review of education, policy and research in England. AB - OBJECTIVE: The objective of this narrative review was to identify and describe the current policy, education and research related to community pharmacy and medication adherence in England. METHODS: Medline, Embase, International Pharmaceutical Abstracts and Pharmline were used to search for relevant research articles. Current policy documents were identified via the websites of the Department of Health in England, the Royal Pharmaceutical Society of Great Britain, the National Pharmacy Association, the Pharmaceutical Services Negotiating Committee and NHS Employers. All pharmacy schools in England were contacted to obtain information about the adherence-related courses they provide to undergraduate and postgraduate pharmacy students. RESULTS: National policies and guidelines in England are conducive to an increasing role for community pharmacists to support patients with medication adherence. Many pharmacy schools cover the issue of adherence in their undergraduate and postgraduate courses. Research in this area has tested the effectiveness of pharmacists providing adherence support in the form of compliance aids, education, involvement in discharge planning, and tailored interventions. CONCLUSION: In community pharmacy in England, current policy and funding arrangements suggest there is great scope for pharmacists to support patients with medication adherence. Further research is necessary to identify the most useful, cost-effective and sustainable approach in practice. PMID- 25132875 TI - Pharmacists' perceptions of the impact of care they provide. AB - Limitations on health care resources necessitate careful focus on activities that lead to the greatest improvement in patient outcomes. Despite the importance of aligning pharmacists' time with activities deriving the most impact, there is a paucity of literature on the correlations between pharmacists' perceptions of the impact of their activities, how they actually spend their time and how these align with published evidence of impacts on patient outcomes. OBJECTIVE: To reveal hospital pharmacists' perceptions of the impacts of their clinical activities and to characterize the correlation between the activities performed and both their perceptions of and the published evidence for their impacts on patient care. METHODS: Observational qualitative interviews and quantitative questionnaires were conducted with each participant (N=21) to characterize their work day and determine their perceptions of the impact of their activities. A systematic literature review catalogued pharmacists' activities with impact on patient outcomes. Primary endpoint: degree of correlation in three pair-wise comparisons between pharmacists' perceptions of impact, time allotted to activities, and published evidence of impact. RESULTS: Pharmacists' time spent was positively and significantly correlated with their perception of impact (P=0.037) but not with the published evidence of impact (in either of the two analytical scenarios). The correlation between published evidence and pharmacists' perceptions of impacts was on the threshold of statistical significance with a moderate strength of association in one of the two analytical scenarios used. CONCLUSIONS: Pharmacists dedicate more of their clinical time to activities they perceive to have greater impact. However, these perceptions and their time allocation does not correlate well with published evidence, and some misperceptions about impacts deserve correction. More rigorous research is needed to quantify the value of pharmacist services to the health care system, however designing such studies to isolate the value of specific activities will be challenging. PMID- 25132876 TI - Parent's knowledge and management of their children's ailments in Malaysia. AB - Minor ailments like sore throat, fever, cough and diarrhea can be relieved with over-the-counter (OTC) medications such as paracetamol or other traditional remedies, without seeking for consultation from general practitioners. Parents usually take the responsibility to come up with some kind of treatment for their children. OBJECTIVE: (1) to evaluate the parents' medical knowledge about OTC medicines which are usually used by the parents to treat their children and (2) to evaluate the parents' management in dealing with their children's ailments, and (3) to evaluate the association between medical knowledge and the management of children's ailments related to medicine use among the parents. METHODS: A cross-sectional survey was conducted to measure the parents' knowledge about their children's ailments. Subjects were selected and information was obtained in September 2008. Non-probability convenient sampling method was used. Parents were recruited from the general public to answer the questionnaires. RESULTS: 197 parents filled in the questionnaires. From the total respondents, 48.2% of them were male. This study showed that most respondents have medium knowledge (6.11 SD=3.6) and a moderate management (4.39 SD=2.7). The results showed that there is a significant difference between the knowledge and the management level of ailments (P=0.033). Regarding the education level of the parents and the socioeconomic status, the p-value showed there was a significant difference between parents' knowledge and their education level (P=0.012). CONCLUSION: This study showed that parents have inadequate knowledge and some misconception about how to go about treating their children when they are unwell. It is hoped that by identifying weak areas in parents' management to their children's ailments, better planned educational and behavioral modification efforts can be made to elevate the knowledge level among the parents when they medically treat their children. PMID- 25132877 TI - The impact of an immunization training certificate program on the perceived knowledge, skills and attitudes of pharmacy students toward pharmacy-based immunizations. AB - OBJECTIVE: To assess the impact of a national immunization training certificate program on the perceived knowledge, skills and attitudes of pharmacy students toward pharmacy-based immunizations. METHODS: The study design utilized a pre- and post-survey administered to pharmacy students before and after the American Pharmacists Association's (APhA) Pharmacy-Based Immunization Delivery program. The primary outcome explored was a change in the perceived knowledge, skills, and attitudes of the pharmacy students. A five-point Likert scale (i.e. strongly agree = 5, strongly disagree = 1) was used for measuring the main outcomes, which was summated by adding the individual item scores in each section to form a composite score for each outcome. RESULTS: The certificate training program resulted in a significant improvement in knowledge (38.5% increase in score, p<0.001) and skills (34.5% increase in score, p<0.001), but not attitudes (1% increase in score, p=0.210). CONCLUSIONS: The national immunization training certificate program had a positive impact on the perceived knowledge and skills of pharmacy students. However, no change was observed regarding students' perceived attitudes toward pharmacy-based immunizations. PMID- 25132879 TI - Willingness to pay for a pharmacist's dispensing service: a cross-sectional pilot study in the state of Penang, Malaysia. AB - OBJECTIVE: The aim of this pilot study was to assess the value of the dispensing service of pharmacists from the general public's perspective using the contingent valuation technique in the State of Penang, Malaysia. METHODS: Participants were conveniently sampled from malls and were given a self-completed questionnaire that collected the patient's demographic information and their knowledge about the pharmacist's dispensing service. They were then presented with a description of the pharmacist's dispensing service, the risk of medication errors in prescriptions and their consequences, and the risk reduction of medication errors associated with pharmacist intervention. The willingness to pay (WTP) of the participants was later assessed using a contingent valuation interview that asked the likelihood and maximum amount they were willing to pay. RESULTS: In the study, 100 people participated, and 57% were aged between 18 and 35 years. Of these participants, 51% were women, and 46% of them earned more than 1000 MYR (285.71USD) per month. In addition, 8% of the participants had never visited a community pharmacy. Finally, 67% of the participants were willing to pay for the pharmacists' dispensing service, and the median amount that the participants were willing to pay was 10 MYR (2.86USD). The WTP amount was moderately correlated with their knowledge of the community pharmacist's dispensing services (r=0.377, p=0.02). CONCLUSION: Generally, the public valued the pharmacist's dispensing service. Their acceptance can be further improved by educating the public on the role of the pharmacist. PMID- 25132878 TI - Pharmacists' attitude, perceptions and knowledge towards the use of herbal products in Abu Dhabi, United Arab Emirates. AB - OBJECTIVE: The purpose of the study was to assess pharmacists' current practice, perception and knowledge towards the use of herbal products in Abu Dhabi, United Arab Emirates (UAE). The study assessed the need for incorporating herbal medicine as a separate topic in under- graduate pharmacy student curricula. METHODS: The study was done on 600 pharmacists employed in Abu Dhabi, who were contacted electronically, out of which 271 had completed the survey. The data was collected using a structured questionnaire. RESULTS: Pharmacists' use of herbal products is high in the UAE, as they have a high belief on the effectiveness of herbal products, and only age was found to be the most predominant variable that was influencing pharmacists' personal use of herbal products (p-value=0.0171). Pharmacists were more knowledgeable on the uses/indications of herbal products (47%) rather than on other areas. Knowledge of the dispensing mode (prescription only or over the counter medicines) mandated by the Ministry of Health was quite good, however, it is to be noted that the source of information on the dispensing mode was provided by medical representatives (48%). Knowledge of dispensing mode of herbal products was found to be significantly influenced by the place of work with more knowledge of the dispensing mode by pharmacists working in the private sector (p-value 0.0007). The results from the study also underscores the need for including herbal medicine as a separate topic in pharmacy college curriculum and to provide for more seminars and continuing pharmacy education programs targeting pharmacists in the Emirate of Abu Dhabi. CONCLUSIONS: Pharmacists need to be informed on indications, drug interactions, adverse events and precautions of herbal products. Concerned bodies must also provide them with regular continuing education programs apart from putting their efforts to incorporate relevant topics on herbal medicine in the pharmacy students' curriculum. PMID- 25132880 TI - Barriers to medication counselling for people with mental health disorders: a six country study. AB - Provision of medication information may improve adherence and prevent medication related problems. People with mental health disorders commonly receive less medication counselling from pharmacists than people with other common long term and persistent disorders. OBJECTIVE: The objective of this study was to compare and contrast barriers pharmacy students perceive toward providing medication counselling for people with mental health disorders in Australia, Belgium, Estonia, Finland, India and Latvia. METHODS: Barriers identified by third-year pharmacy students as part of the International Pharmacy Students' Health Survey were content analysed using a directed approach. Students' responses were categorised as pharmacist related, patient related, health-system related, or social or cultural related. Quantitative data were analysed using SPSS version 14.0. RESULTS: Survey instruments were returned by 649 students. Of the respondents, 480 identified one or more barriers to medication counselling for people with mental health disorders. Patient related factors accounted for between 25.3% and 36.2% of barriers identified by the pharmacy students. Pharmacist related factors accounted for between 17.6% and 45.1% of the barriers identified by the pharmacy students. Students in India were more likely to attribute barriers to pharmacist and social and cultural related factors, and less likely to health-system related factors, than students studying in other countries. CONCLUSION: The nature of barriers identified by pharmacy students differed according to the country in which they studied. Undergraduate and postgraduate pharmacy education programs may need to be amended to address common misconceptions among pharmacy students. PMID- 25132881 TI - Comparison of prescribing criteria in hospitalised Australian elderly. AB - The Beers criteria (2003) and McLeod criteria (1997) have been applied internationally to quantify inappropriate prescribing in elderly populations. Similarly, guidelines have been published locally by the National Prescribing Service (NPS). OBJECTIVE: This study aimed to adapt, evaluate and compare the utility of these three established criteria in measuring prescribing appropriateness in a sample of hospitalised elderly patients. METHODS: Initial refinement of the criteria produced versions applicable to Australian practice. Inpatient records of 202 patients aged 65 years or older in six wards of the Princess Alexandra Hospital, Brisbane, Australia, were reviewed using the adapted criteria. 'Potentially inappropriate' prescribing was descriptively analysed using relevant denominators. RESULTS: The adapted criteria collectively listed 70 'potentially inappropriate' medicines or drug groups and 116 'potentially inappropriate' prescribing practices. Patients (mean age 80.0; SD=8.3 years) were prescribed, a median of eight medicines (SD=4.0). At least one 'potentially inappropriate' medicine was identified in 110 (55%) patients. 'Potentially inappropriate' prescribing practices averaged 1.1 per patient (range 1-6). The adapted Beers criteria identified more 'potentially inappropriate' medicines/practices (44%, 101/232) than the McLeod criteria (41%) and NPS criteria (16%). Aspirin, benzodiazepines, beta-blockers and dipyridamole were most commonly identified. CONCLUSION: The Beers and McLeod criteria, developed internationally, required considerable modification for local prescribing. The three criteria differed in their focus and approaches, such that development and validation of national criteria, using the key features of these models, is recommended. There is potential to apply validated guidelines in clinical practice and review of prescribing, but only to supplement clinical judgement. PMID- 25132882 TI - Pharmacists' participation in the documentation of medication history in a developing setting: An exploratory assessment with new criteria. AB - OBJECTIVE: To assess the impact of pharmacists' participation on the frequency and depth of medication history information documented in a developing setting like Nigeria. METHOD: The study consisted of two phases. The first phase was a baseline cross-sectional assessment of the frequency and depth of medication history information documented by physicians in case notes of systematic samples of 900 patients that were stratified over 9 Medical outpatients Units at a premier teaching hospital in south western Nigeria. The second phase was an exploratory study involving 10 pharmacists who conducted cross-sectional medication history interview for 324 randomly selected patients. RESULTS: 49.2% of patients, whose medication history were documented at the baseline, by physicians, were males; while 50.3% of patient interviewed by pharmacists were male. Mean age (SD) of males and females whose medication histories were documented by physicians and pharmacists were 43.2 (SD=18.6), 43.1 (SD=17.9) years and 51.5 (SD=17.6), 52.1 (SD=17.4) years respectively. The frequency of medication history information documented by pharmacists was significantly higher for twelve of the thirteen medication history components (P < 0.0001). These include prescription medicines; over the counter medicines; source of medicines; adverse drug reactions; allergy to drugs, allergy to foods, allergy to chemicals; patient adherence; alcohol use; cigarette smoking; dietary restrictions and herbal medicine use. The depth of medication history information acquired and documented by pharmacist was significantly better for all the thirteen medication history components (P<0.0001). CONCLUSION: Pharmacists' participation resulted in significant increase in frequency and depth of medication history information documented in a developing setting like Nigeria. The new medication history evaluation criteria proved useful in assessing the impact of pharmacists' participation. PMID- 25132883 TI - Evaluating the impact of new anticoagulants in the hospital setting. AB - The short-comings of current anticoagulants have led to the development of newer, albeit more expensive, oral alternatives. OBJECTIVE: To explore the potential impact the new anticoagulants dabigatran and rivaroxaban in the local hospital setting, in terms of utilisation and subsequent costing. METHOD: A preliminary costing analysis was performed based on a prospective 2-week clinical audit (29th June - 13th July 2009). Data regarding current anticoagulation management were extracted from the medical files of patients admitted to Ryde Hospital. To model potential costing implications of using the newer agents, the reported incidence of VTE/stroke and bleeding events were obtained from key clinical trials. RESULTS: Data were collected for 67 patients treated with either warfarin (n=46) or enoxaparin (n=21) for prophylaxis of VTE/stroke. At least two-thirds of all patients were deemed suitable candidates for the use of newer oral anticoagulants (by current therapy: warfarin: 65.2% (AF), 34.8% (VTE); enoxaparin: 100%, (VTE)). The use of dabigatran in VTE/stroke prevention was found to be more cost- effective than warfarin and enoxaparin due to significantly lower costs of therapeutic monitoring and reduced administration costs. Rivaroxaban was more cost-effective than warfarin and enoxaparin for VTE/stroke prevention when supplier-rebates (33%) were factored into costing. CONCLUSION: This study highlights the potential cost- effectiveness of newer anticoagulants, dabigatran and rivaroxaban, compared to warfarin and enoxaparin. These agents may offer economic advantages, as well as clinical benefits, in the hospital-based management of anticoagulated patients. PMID- 25132884 TI - Evaluation of pharmacy students' clinical interventions on a general medicine practice experience. AB - As colleges of pharmacy prepare a new generation of practitioners, it is important that during practice experiences students learn the impact of clinical interventions. For over ten years, pharmacy students have been a vital part of the multidisciplinary team at the military treatment facility. The overall impact of the student interventions on patient care has not been evaluated. To evaluate the impact, the students began documenting their clinical interventions in Medkeeper RxInterventionsTM, an online database. The program is used to document faculty and fourth year pharmacy students' pharmaceutical interventions. OBJECTIVE: The objective of this study was to analyze the interventions completed by fourth year pharmacy students during a general medicine advanced pharmacy practice experience at a military treatment facility. METHODS: The students completing their general medicine advanced pharmacy practice experience at the military treatment facility are responsible for self reporting all interventions made during clinical rounds into the Medkeeper RxInterventionTM database. The researchers retrospectively collected and analyzed interventions made from June 2008 to June 2009. RESULTS: The total number of interventions recorded by 8 fourth year pharmacy students was 114. Students averaged a number of 14.3 interventions during an eight week practice experience. Students spent an average of 5 minutes per intervention. Ninety- five percent of the interventions were accepted. CONCLUSION: Fourth year pharmacy students' recommendations were accepted at a high rate by resident physicians. The high acceptance rate may have the ability to positively impact patient care. PMID- 25132885 TI - Defining bioidentical hormones for menopause-related symptoms. AB - In the last decade, the use of bioidentical hormones (BHs) to treat menopause related symptoms has become increasingly popular. However, the many different definitions of BHs have led to a great deal of confusion often making it difficult for health care providers to discuss this area with patients. OBJECTIVE: The purpose of this paper was to produce a concise definition of bioidentical hormones, based on a review of the literature. METHODS: Searches, using systematic review methodology, were conducted from inception to June 2010 in PubMed, EMBASE, IPA, The Journal of International Compounding and the Internet to identify definitions of bioidentical hormones. There were no restrictions on type, date or language of publication. Included papers/website included those that contained a definition of BHs. Definitions were extracted, similarities and differences summarized, and these were then examined to produce a concise definition. RESULTS: Sixty-three definitions were found. Based on the analysis of similarities and differences, the following definition, comprised of three components (term being defined; category to which term belongs; distinctive characteristics of term) was produced: "Bioidentical hormones are chemical substances that are identical in molecular structure to human hormones." CONCLUSIONS: This definition clearly and concisely explains the meaning of BHs which should lead to a common understanding of the term and limit confusion among health care providers, the general public and the scientific community. PMID- 25132886 TI - Comparison of prescribing and dispensing processes between veterinarians and pharmacists in New Zealand: Are there opportunities for cooperation? AB - BACKGROUND: Prescribing and dispensing of medicines are fundamental processes in providing healthcare for both human and animal patients. There has been recent discussion in the literature to advocate for increased co-operation between pharmacists and veterinarians, however there is little data available about veterinary prescribing and dispensing processes. OBJECTIVE: The aims of this study were to gain information on veterinary prescribing and dispensing processes for companion animals in the Dunedin region of New Zealand. METHODS: Open interviews were conducted with a selection of five veterinarians at practices in Dunedin. All interviews were transcribed verbatim. RESULTS: In New Zealand almost all dispensing of medicines for animals is carried out by veterinarians or their staff. There is a lack of standard treatment guidelines and a lack of regulation around the treatment period for which medicines can be dispensed at one time (i.e. period of supply). Medicines for animals are sometimes dispensed by community pharmacies, where clients are experiencing financial difficulties or when particular medicines are not held by veterinary practices. Record keeping requirements and practices for veterinarians are similar to those for community pharmacies. CONCLUSIONS: Processes undertaken by veterinarians in terms of prescribing and dispensing were similar to pharmacists' practices for human patients and so there is opportunity for collaboration between the two professions. Pharmacists also have complementary knowledge about dosing and formulating medicines that can assist in delivering optimal healthcare to animal patients. PMID- 25132887 TI - Hyperlipidemia medication management in patients admitted for a myocardial infarction. AB - OBJECTIVES: The purpose of this study is to determine the percentage of patients admitted for acute myocardial infarction currently prescribed a statin, with low density lipoprotein (LDL) <100 mg/dL, and high-density lipoprotein (HDL) <50 mg/dL for men and <55 mg/dL for women and evaluate their medication management with a focus on niacin initiation. METHODS: This was a retrospective study from 12/07 to 12/09, conducted at a private, community hospital. Inclusion criteria required patients to have an acute myocaridal infarction (AMI) ICD-9 code, troponin >=0.2 ng/dL and lipid panel performed within 96 hours of troponin. Patients with a triglyceride level > 400 mg/dL were excluded. The residual risk population consisted of patients currently taking a statin with LDL <100 mg/dL and HDL <50/55 mg/dL. Patients were excluded from the residual risk population if they were on niacin, had an allergy to or previously failed niacin therapy, or expired within 72 hours. RESULTS: A total of 553 patients experiencing an AMI had lipid panels available for evaluation. The mean LDL was 97.3 +/- 36.0 mg/dL, mean HDL was 33.5 +/- 11.1 mg/dL, and mean triglycerides were 133.1 +/- 71.3 mg/dL. The majority of patients (n=521, 94.2%) had an HDL < 50 or 55 mg/dL respective of gender. Ninety-two (80.0%) residual risk patients had no change in their home lipid medications post AMI. Fifteen (13.0%) residual risk patients had their dose of statin medication increased. Seven (6.1%) residual risk patients were initiated on niacin. CONCLUSIONS: The study results confirm an existence of a residual risk population with nearly 25% of AMI patients meeting the criteria. The results also confirm a low incidence of medication intervention in the residual risk population post AMI (20.0%) regarding lipid therapy, including the initiation of niacin in only 6.1% of patients. PMID- 25132889 TI - Unlocking the condoms: The effect on sales and theft. AB - Community pharmacies may place condoms in locked displays or behind glass, thereby reducing access and consequent use. OBJECTIVE: Quantify sales and theft of condoms when condoms were unlocked and removed from behind glass in grocery pharmacies. METHODS: Design. In this pilot study, condom displays were unlocked in selected pharmacies for three months. Participants. Eight grocery pharmacies in central Iowa agreed to participate. Intervention. Stores provided inventory at baseline, sales/theft thereafter in three monthly reports and sales for the same period one-year earlier. Outcome measures. Descriptive statistics quantified condom theft and sales. Number of pharmacies leaving condoms unlocked after the intervention was determined. RESULTS: Theft varied by pharmacy and ranged from an average of 1.33 boxes (units) per month to 27.33 per month. All stores experienced some increase in sales during the intervention. Two locations decided to re-lock their displays, only one indicated theft as the reason. CONCLUSION: After removing condoms from locked displays, more condoms were purchased and stolen from the study pharmacies. Sales outweighed theft in all pharmacies. PMID- 25132888 TI - Evaluation of the community pharmacist's behavior towards a prescription of antidiabetic and antiasthma drugs. AB - OBJECTIVE: The objective of this study is to assess the performance of community pharmacist towards antidiabetic and antiasthma prescriptions, and also to assess the lack of information provided by community pharmacists regarding patient counseling and missing data, using a simulated patient technique. METHODS: A prescription including antidiabetic and antiasthma drugs was used by simulated patient to assess community pharmacist's performance in 194 pharmacies. A performance assessment sheet was used to measure the patient counseling process. A quantitative descriptive and comparative analysis was done for the collected data. Pearson chi-square test (crosstabs) was used with a level of significance 95%). RESULTS: The analysis of the 194 pharmacies visited revealed that most of the pharmacists were male (61%), Arabs (35%) and Indians (55%) with some other nationalities. The dispensing time in the pharmacy ranged between 2 to 10 minutes. Spending time with patients was not affected by gender (p-value 0.087), slightly affected by nationality (p-value 0.04), and highly affected by age (p value 0.002) leaning towards older pharmacists who spent more time with patients than younger pharmacists. Most pharmacists (90%) started preparing the prescription once they received the prescription with no actual prescription screening. fifty five percent of the pharmacists asked about the duration of the treatment after preparing the prescription. ninety six percent did not counsel patients about diet, exercise and lifestyle changes. Less than 40% asked if the prescription was intended to be used for the same patient. CONCLUSION: This study recommends that health authorities consider follow up plans in order to ensure the best pharmaceutical care is provided by community pharmacies. PMID- 25132890 TI - RETRACTED by plagiarism: Highly active antiretroviral therapy induced adverse drug reactions in Indian human immunodeficiency virus positive patients. AB - OBJECTIVE: To assess the incidence, severity pattern, causality, predictability and preventability of adverse drug reactions (ADRs) and to identify risk factors for adverse drug reactions in highly active antiretroviral therapy. METHODS: Enrolled patients were intensively monitored for ADRs to highly active antiretroviral therapy. Predictability was assessed based on history of previous exposure to the drug or literature incidence of ADRs. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using modified Hartwig and Siegel scale. Multivariate logistic regressions were used to identify the risk factors for ADRs. RESULTS: Monitoring of 130 retropositive patients by active pharmacovigilance identified 74 ADRs from 57 patients. Anemia and hepatotoxicity were the most commonly observed ADRs. The organ system commonly affected by ADR was red blood cell (21.4%). The ADRs were moderate in 77% of cases. Type A reactions (77%) were more common. A total of 10.8% ADRs were definitely preventable. The incidence rate of ADRs (65.9%) was highest with Zidovudine + Lamivudine + Nevirapine combination. A total of 84% interruptions to highly active antiretroviral therapy were due to toxicity. CD4 less than 200 cells/MUl, female gender and tuberculosis were observed as risk factors for ADRs. CONCLUSION: Incidence of ADRs in intensively monitored patients was found to be 43.8%. Anemia in HIV patients is an influential risk factor for occurrence of ADRs. With the increasing access to antiretroviral in India, clinicians must focus on early detection and prevention of ADRs to highly active antiretroviral therapy. PMID- 25132891 TI - Comparison of robotic and open partial nephrectomy: Single-surgeon matched cohort study. AB - INTRODUCTION: We present comparative outcomes among matched patients who underwent robotic partial nephrectomy (RPN) or open partial nephrectomy (OPN) by a single surgeon at a single institution. METHODS: We reviewed the medical records of 200 patients who underwent RPN (n = 100) or OPN (n = 100) between May 2003 and May 2013. The patients who underwent RPN were matched for age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) score, as well as tumour size, side and location. Perioperative outcomes were compared. RESULTS: There was no significant difference between the 2 cohorts with respect to patient age, BMI, ASA score, preoperative glomerular filtration rate, tumour size and the R.E.N.A.L. nephrometry score. The mean operative time was longer in the RPN group, but there were no significant differences with respect to warm ischemic time and postoperative renal function. The length of hospitalization and use of postoperative analgesics (ketoprofen) were more favourable in the RPN cohort. There was no significant difference in the mean estimated blood loss, transfusion rate, or complications between the cohorts. CONCLUSIONS: Considering the perioperative and postoperative parameters, RPN is a viable option as a nephron sparing surgical procedure for small renal masses that yields outcomes comparable to those achieved with OPN. Despite matched cohort analysis among patients who underwent PN by a single surgeon, there may be inherent selection bias; therefore future prospective trials are needed. PMID- 25132893 TI - High-grade microscopic hematuria in adult men can predict urothelial malignancy. AB - INTRODUCTION: Microscopic hematuria in men younger than 40 is a confusing issue to urologists, especially when these men have normal radiological findings. We report our experience in looking for urologic malignancy in this group of patients. METHODS: We conducted a prospective study for men with vague urological symptoms. We included men under 40 years old, men with microscopic hematuria greater than 25 red blood cells/high power field in 2 properly collected mid stream urine samples, and men with free urine culture and normal multiphasic computed tomography abdomen and pelvis studies. All patients underwent diagnostic cystoscurethroscopy. If there were no lesions, multiple random biopsies were taken. In cases of apparently normal cystoscopic findings and associated renal colic, uretroscopy was done to the suspected side. RESULTS: Only 20 patients fulfilled our inclusion criteria. The mean age of the patients were 34; 2 patients presented with pain. The other 18 patients were presenting with mild recurrent lower urinary tract symptoms. Cystoscopy showed small papillary low grade tumour in 3 patients. All random biopsies were free of malignancy. Unilateral uretroscopy for the 2 cases presented with pain detected carcinoma in situ in one of them. CONCLUSION: Cystoscopy is highly recommended for young adult men, with significant levels of microscopic hematuria, due to the 20% incidence rate of associated urological malignancy. Random bladder biopsies, in the absence of suspicious lesions, have no diagnostic role, and should not be done. Uretroscopy is advised for patients with microscopic hematuria and loin pain, even in the absence of suspicious radiological findings. PMID- 25132894 TI - A clinical study comparing BIVAP saline vaporization of the prostate with bipolar TURP in patients with prostate volume 30 to 80 mL: Early complications, physiological changes and postoperative follow-up outcomes. AB - INTRODUCTION: We compare BIVAP saline vaporization of the prostate with bipolar transurethral resection of the prostate (TURP) in the treatment of benign prostatic hyperplasia. METHODS: In total, we included 86 patients treated with BIVAP (n = 44) and bipolar TURP (n = 42). The inclusion criteria were maximum urinary flow rate (Qmax) <=10 mL/s, International Prostate Symptom Score (IPSS) >=16, and prostate volume measured with transrectal ultrasound scan between 30 and 80 mL. Serum electrolyte, hemoglobin, and hematocrit levels were determined preoperatively and postoperatively. All patients were evaluated at the postoperative first and third months and the IPSS score, post-void residual urinary volume (PVR), Qmax, and average urinary flow rate (Qave) were compared. Statistical analyses were performed using SPSS 16.0 program and statistical significance was set at p < 0.05. RESULTS: Preoperative demographic characteristics were similar in the 2 groups. The mean operation time was significantly higher (p = 0.02) and hospitalization time was significantly lower (p = 0.04) in the BIVAP group when compared to the bipolar TURP group. There was no significant difference between 2 groups in terms of preoperative and postoperative serum electrolyte, hemoglobin and hematocrit levels. Postoperative complication rates were similar in the 2 groups. The only exception was the rate of severe dysuria, which was significantly higher in the BIVAP group. No statistical difference was noted between the groups in terms of postoperative follow-up results. CONCLUSION: Bipolar TURP is a safe and highly effective technique which can be used in the surgical treatment of benign prostatic obstruction with minimal side effects. BIVAP saline vaporization of the prostate seems to be a potential alternative to bipolar TURP with shorter hospitalization time. PMID- 25132892 TI - Predicting the Gleason sum of a patient with a prostate biopsy core Gleason <=7 and a prostate biopsy core Gleason >=8. AB - INTRODUCTION: We review a subset of men who had discordant prostate biopsy sums and were treated with radical prostatectomy. METHODS: Consecutive patients treated with radical prostatectomy at The Ottawa Hospital between 2000 and 2012 were reviewed. Those with at least 1 prostate biopsy core of Gleason sum >=8 and at least 1 prostate biopsy core of Gleason sum <=7 cancer were included. RESULTS: Of the 764 radical prostatectomies, 661 (87%) were eligible for the study and 35 (5%) met inclusion criteria. Of these, only 16 (46%) had prostatectomy Gleason sum of >=8. When the highest biopsy core was Gleason sum 8 (n = 24), only 7 (29%) had a prostatectomy Gleason sum >=8. When the highest biopsy core was Gleason 9 (n = 11), 9 (82%) had a prostatectomy Gleason sum >=8 (relative risk [RR] 2.8; p = 0.004). Patients with clinical T3 tumours were at higher risk of Gleason sum >=8 compared to cT1 patients (RR 3.7; p = 0.008). Patient age (p = 0.89), preoperative prostate-specific antigen (p = 0.34), prostate volume (p = 0.86), number of biopsy cores (p = 0.18), and proportion of biopsy cores with cancer (p = 0.96) were not strongly associated with risk of prostatectomy Gleason sum >=8. CONCLUSION: These data should be considered when assigning patients into prognostic risk categories based on prostate biopsy information. Further study to verify our findings using larger samples is warranted. PMID- 25132895 TI - [Not Available]. PMID- 25132896 TI - Retention of robot-assisted surgical skills in urological surgeons acquired using Mimic dV-Trainer. AB - INTRODUCTION: We assess the retention of robot-assisted surgical skills among urologic surgeons. METHODS: The robot-assisted surgery skills of 20 urologic surgeons were assessed using a Mimic dV-Trainer program (Mimic Technologies, Inc., Seattle, WA) consisting of 6 tasks. These 20 surgeons had no previous experience either using the Mimic dV-Trainer or acting as the main surgeon in robot-assisted surgery. The surgeons completed the program 4 times in a row; after 1 year, they completed it again for a fifth time. Performance scores were recorded using the Mimic dV-Trainer's built-in algorithm. RESULTS: For all 6 tasks, there were significant improvements to the scores in the fourth trials compared with those in the first trials. The scores in the fifth trials did not significantly decline compared with those in the fourth trials. There was no significant difference between the fifth trial scores of surgeons with laparoscopic surgery skills/experience and those without. CONCLUSION: Our results indicate that fundamental robot-assisted surgical skills can be retained in the long-term after they are acquired. PMID- 25132897 TI - Emphysematous cystitis and necrotizing fasciitis. AB - Emphysematous cystitis is an uncommon and often severe infectious condition of the bladder that usually affects women and diabetics. We report a case of a 62 year-old male patient who presented with concomitant emphysematous cystitis and necrotizing fasciitis of the right leg. The patient was initially managed with emergent disarticulation of the right leg. Tissue cultures were positive for Ciprofloxacin-resistant Klebsiella pneumoniae. He was treated with Piperacillin Tazobactam; however, due to the failure of conservative management of the condition, the patient underwent a cystoprostatectomy with ileal conduit. To our knowledge, this is the first report of concomitant emphysematous cystitis and necrotizing fasciitis requiring aggressive surgical intervention for both diseases. PMID- 25132898 TI - A surgical challenge: Idiopathic scrotal elephantiasis. AB - Scrotal elephantiasis is a condition rarely encountered in developed nations. It is endemic in tropical regions due to the presence of filariasis (Wucheria bancrofti). We report 2 cases of idiopathic scrotal elephantiasis in Canadian citizens with no history of travel to endemic filariasis regions, malignancy, surgery or radiation. Both patients underwent complete excision of the involved tissue with reconstruction. We found that for advanced cases of scrotal lymphedema, surgery is currently the only solution. In our cases of advanced idiopathic disease, surgical treatment combining the expertise of a plastic surgeon and a urologist provided a successful functional and cosmetic result. PMID- 25132899 TI - Standardized follow-up program may reduce emergency room and urgent care visits for patients undergoing radical prostatectomy. AB - INTRODUCTION: The objective of the current study was to determine the impact of a standardized follow-up program on the morbidity and rates of hospital visits following radical prostatectomy (RP) in a tertiary, non-teaching urologic centre. METHODS: Patients who underwent a RP in 2008 were retrospectively evaluated in this study. Postoperative morbidity for the entire cohort was assessed using the Modified Clavien Scale (MCS). Those patients readmitted to hospital or who visited an urban or rural emergency department (ED) within 90 days of surgery were further evaluated to determine the reason for readmission. RESULTS: At our centre, 321 patients underwent RP in 2008 by 11 surgeons. Of the 321 patients, 77 (24.0%) visited an ED within 90 days, and 14 were readmitted to hospital, with an additional patient readmitted directly (with a total 15 readmissions, 4.7% overall). No patients died within the study period. In 2009 we launched a pilot study wherein 115 RP patients received scheduled and on-demand follow-up care by a dedicated nurse between May and November. We found that 90-day readmission rates among this cohort dropped to 5% and 2.6% for ED visits and hospital readmission, respectively. CONCLUSIONS: At our tertiary non-teaching centre, a significant number of patients presented back to hospital within 90 days following RP. Most of these patients (80.8%) were managed entirely through an outpatient ED, and many visits were for routine postoperative care. Only 18.2% (4.7% of the 321 prostatectomy patients) were readmitted to hospital. These data point to a need for enhanced postoperative support of patients to reduce costly and often unnecessary visits to acute care EDs. This conclusion is supported by our early experience. Limitations include retrospective design, and variability in practice of surgeons in this study. PMID- 25132900 TI - Squamous cell carcinoma of the suprapubic tract: A rare presentation in patients with chronic indwelling urinary catheters. AB - Squamous cell carcinoma (SCC) of the bladder is uncommon, but can arise in the setting of long-term bladder catheterization and chronic inflammation. SCC can arise primarily from the suprapubic catheter tract, but fewer than 10 such cases have been reported. We document 2 cases of SCC arising from the suprapubic tract associated with chronic indwelling urinary catheters. SCC must be differentiated from granulomatous conditions, which are quite common in patients with suprapubic catheters. PMID- 25132901 TI - Entertainment Venue Visiting and Commercial Sex in China. AB - Entertainment venues in China play an important role in the sexually transmitted disease (STD)/HIV epidemic. Most previous studies have focused on sex workers working in entertainment venues, but little is known about their clients. This study investigated the perceptions and behavior of the patrons visiting entertainment venues. Qualitative in-depth interviews were conducted with 30 male market vendors who visited entertainment venues at least once in the past 3 months in an eastern city in China. Information about their risky behavior, attitude toward commercial sex, and STD/HIV prevention approaches was collected. Saunas, karaoke bars, and massage centers are the most frequently visited entertainment venues. Seventy-three percent of study participants reported purchasing commercial sex at these entertainment venues. Participants expressed a very liberal attitude toward commercial sex. Seeking commercial sex was perceived as a characteristic of a male's nature. The perceived risks of STD/HIV infection do not deter participants from engaging in commercial sex. Commercial sex clients reported irregular condom use and a number of other misperceptions and improper practices toward preventing STD/HIV infection. Venue-based intervention is urgently needed to target the population. The sex workers themselves could potentially serve as "health educators" to communicate prevention information to their clients and encourage safer sex behavior. PMID- 25132902 TI - Aortic arch calcification, procedural times, and outcomes of endovascular treatment in patients with acute ischemic stroke. AB - OBJECTIVE: To determine the frequency of aortic arch calcification and it's relationship with procedural times, angiographic recanalization, and discharge outcomes in acute ischemic stroke patients undergoing endovascular treatment. METHODS: The thoracic component of computed tomographic (CT) angiogram were reviewed by an independent reviewer to determine presence of any calcification; and the severity of calcification was graded as follows: mild, single small calcifications; moderate, multiple small calcifications; or severe, one or more large calcifications. RESULTS: Aortic arch calcification was present in 120 (62.4%) of 188 patients and severity was graded as mild (n=24), moderate (n=44), and severe (n=52). Compared with patients without calcification, the mean intracranial access time (minutes +/- SD) was similar among patients with aortic arch calcification (70 +/- 31 versus 64 +/- 31, p=0.9). The mean time intracranial access time increased with increasing severity of aortic arch calcification (61+/-27, 67+/-29, and 74+/-34, p=0.3). Patients with aortic arch calcification had similar rates of complete or partial recanalization [85 (71%) versus 50 (76%)], p=0.6) but lower rates of favorable outcomes [modified Rankin scale 0-2] at discharge 27 (22%) versus 26 (39%), p=0.02). CONCLUSIONS: A high proportion of acute ischemic stroke patients have aortic arch calcification which is associated with lower rates of favorable outcome following endovascular treatment. ABBREVIATIONS: SDstandard deviationICHintracerebral hemorrhageNIHSSNational Institutes of Health Stroke ScaleTIAtransient ischemic attackICHintracerebral hemorrhagemRSmodified Rankin scale. PMID- 25132903 TI - Case report: Intra-procedural aneurysm rupture during endovascular treatment causing immediate, transient angiographic vasospasm. AB - INTRODUCTION: Cerebral vasospasm is a major cause of delayed ischemic cerebral injury, typically occurring 3-14 days after subarachnoid hemorrhage (SAH). Ultra early vasospasm is defined as angiographic vasospasm observed within 48 h of SAH onset. Immediate vasospasm at the time of aneurysmal rupture has been suspected, but has not been previously reported. We describe a case of immediate, transient vasospasm following intra-procedural aneurysmal rupture. METHODS: A 55-year-old woman presented with SAH from a ruptured anterior communicating artery aneurysm. Subsequent coil embolization was complicated by an intra-procedural rupture following placement of the initial coil. A follow-up angiogram obtained after 9 min demonstrated moderate-to-severe vasospasm in the A2 segments of both anterior cerebral arteries. RESULTS: A repeat angiogram 20 min later demonstrated complete resolution of the vasospasm. The aneurysm was successfully obliterated with coil embolization. Post-procedure, the patient manifested no clinical vasospasm and made a good neurological recovery. CONCLUSION: We document a case of ultra-early cerebral vasospasm that occurred immediately after an intra-procedural aneurysmal rupture. Catheter-induced vasospasm from mechanical manipulation of extracranial vasculature is well described. However, immediate vasospasm related to extravascular blood has never before been reported. This finding suggests that extravascular blood can have a local direct effect (presumably mechanical) on cerebral blood vessels, and may be an important mechanism for vasospasm. PMID- 25132904 TI - Endovascular treatment of intracranial aneurysms by interventional neurologists: first year single-center experience. AB - BACKGROUND: Endovascular embolization of ruptured intracranial aneurysms provides an adequate treatment and long-term results with less morbidity and mortality (M&M) compared with surgical treatment. Since the last decade more and more ruptured and unruptured intracranial aneurysms (IA) undergo endovascular embolization in the United States. We present our experience of the initial one year periprocedural M&M at Paul L. Foster School of Medicine (PLFSM), Texas Tech Health Science Center (TTUHSC) in El Paso, Texas. METHODS: Demographics, technical aspects of the endovascular procedure and clinical assessment, including several commonly used scales to assess the severity in case of subarachnoid hemorrhage were collected. Perioperative complications were classified as minor and major. All data is prospectively collected in a local database. Only endovascular treated aneurysms were included in the study. RESULTS: During the first year of opening of the interventional neurology program at our school of medicine (March 2011 and March 2012), a total 45 ruptured and unruptured intracranial aneurysms were treated with endovascular embolization. Two thirds of the patients (n = 27) presented with a ruptured IA. Within those with a ruptured aneurysm, the most median Hunt and Hess grade was 3. By large the vast majority of treated IA were in the anterior circulation and more than half measured 7-12 mm. Only three unruptured IA were <7 mm (average 5.5 mm). Complications occurred in seven patients (15%), four of them were minor without any clinical sequelae. The remaining three included; intracranial dissection and aneurysmal rupture resulting in both hemorrhagic or ischemic stroke and death in only one patient. CONCLUSION: The first year experience of interventional neurology services at Paul L. Foster School of Medicine in El Paso, Texas demonstrates successful treatments with comparable national rates of morbidity and mortality. ABBREVIATIONS: ACAAnterior cerebral arteryAcommAnterior communicating arteryESNEndovascular surgical neuroradiologyH&HHunt and Hess scaleIAIntracranial aneurysmICAInternal carotid arteryMCAMiddle cerebral arteryM&MMorbidity and mortalitySAHSubarachnoid hemorrhagePcommPosterior communicating arteryPLFSMPaul L. Foster School of MedicineTTUHSCTexas Tech University Health Science CenterVAVertebral artery. PMID- 25132905 TI - Reversible cerebral vasoconstriction syndrome and nonaneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Reversible cerebral vasoconstriction syndrome was first described by Call, Fleming, and colleagues. Clinically this entity presents acutely, with severe waxing and waning headaches ("thunderclap"), and occasional fluctuating neurological signs. CASE PRESENTATION: We present four subsequent cases of patients with severe thunderclap headache and brain tomography with evidence of subarachnoid hemorrhage. The brain angiogram showed no aneurysm but intracranial vasculopathy consistent with multiple areas of stenosis and dilatation (angiographic beading) in different territories. CONCLUSION: Neurologists should be aware of Call Fleming syndrome presenting with severe headache and associated convexity subarachnoid hemorrhage. After other diagnoses are excluded, patients can be reassured about favorable prognosis with symptomatic management. ABBREVIATIONS: RCVSReversible cerebral vasoconstriction syndromeCTComputed tomographySAHSubarachnoid hemorrhageMRMagnetic resonanceCTAComputed tomography angiographyMRAMagnetic resonance angiography. PMID- 25132906 TI - Pattern of informed consent acquisition in patients undergoing emergent endovascular treatment for acute ischemic stroke. AB - BACKGROUND: Telephone consent and two physician consents based on medical necessity are alternate strategies for time sensitive medical decisions but are not uniformly accepted for clinical practice or recruitment into clinical trials. We determined the rate of and associated outcomes with alternate consenting strategies in consecutive acute ischemic stroke patients receiving emergent endovascular treatment. METHODS: We divided patients into those treated based on in-person consent and those based on alternate strategies. We identified clinical and procedural differences and differences in hospital outcomes: symptomatic ICH and favorable outcome (defined by modified Rankin Scale of 0-2 at discharge) based on consenting methodology. RESULTS: Of a total of 159 patients treated, 119 were treated based on in-person consent (by the patient in 27 and legally authorized representative in 92 procedures). Another 40 patients were treated using alternate strategies (20 telephone consents and 20 two physician consents based on medical necessity). There was no difference in the mean ages and proportion of men among the two groups based on consenting methodology. There was a significantly greater time interval incurred between CT scan and initiation of endovascular procedure in those in whom in-person consent was obtained (117 +/- 65 min versus 101 +/- 45 min, p = 0.01). There was no significant difference in rates of ICH (9% versus 8%, p = 0.9), or favorable outcome at discharge (28% versus 30%, p = 0.8). CONCLUSIONS: Consent through alternate strategies does not adversely affect procedural characteristics or outcome of patients and may be more time efficient than in-person consenting process. PMID- 25132907 TI - Right anterior choroidal artery syndrome: revisited. PMID- 25132908 TI - Ulcerative colitis presenting with bilateral thalamic infarcts due to cerebral sinus thrombosis. PMID- 25132909 TI - Prevalence of vertebral artery origin stenosis and occlusion in outpatient extracranial ultrasonography. AB - BACKGROUND AND PURPOSE: Vertebral artery origin stenosis prevalence. Most data on the prevalence of vertebral artery origin (VAo) disease is derived from hospital based studies of patients with posterior circulation strokes and TIA. The prevalence of VAo disease in patients without posterior circulation symptoms or asymptomatic patients is poorly characterized. Our objective was to examine the prevalence of VAo stenosis and occlusion in consecutive patients, presenting for extracranial ultrasonography at an outpatient laboratory. METHODS: We retrospectively identified 2490 consecutive extracranial duplex studies performed in an ambulatory neurovascular ultrasound laboratory. All studies were reviewed for the presence of >50% VAo stenosis, defined as a PSV > 114 cm/s, and VA occlusion. We also reviewed the prevalence of >50% carotid stenosis, defined as a PSV > 120 cm/s, in the same population, to draw comparisons with VAo stenosis prevalence. RESULTS: We identified right VAo stenosis in 52/1955 (2.7%) and occlusion in 74/ 1955 (3.9%) and left-sided VAo stenosis in 45/1973 (2.5%) and occlusion in 64/1973 (3.6%). The prevalence of having any (either right or left) VAo stenosis or occlusion was 8.2% and 1.4% had bilateral VAo stenosis or occlusion. Right carotid stenosis and occlusion was found in 236/2399 (9.8%) and 53/2399 (2.2%), and left carotid stenosis and occlusion in 236/2397 (9.8%) and 45/2397 (1.9%), respectively. Any carotid disease, either right or left, was present in 18.9% and 4.7% had bilateral carotid disease. CONCLUSION: Although less prevalent than cervical carotid disease, we found that approximately 8% of patients who reported to an ambulatory ultrasound laboratory had >50% VAo disease. PMID- 25132910 TI - Interpretation and Implementation of Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT II). PMID- 25132911 TI - Subclinical Myocardial Disease in Heart Failure Detected by CMR. AB - Noninvasive cardiac imaging plays a central role in the assessment of patients with heart failure at all stages of disease. Moreover, this role can be even more important for individuals with asymptomatic cardiac functional or structural abnormalities-subclinical myocardial disease - because they could have benefits from early interventions before the onset of clinical heart failure. In this sense, cardiac magnetic resonance offers not only precise global cardiac function and cardiac structure, but also more detailed regional function and tissue characterization by recent developing methods. In this section, some of the main methods available for subclinical myocardial disease detection are reviewed in terms of what they can provide and how they can improve heart failure assessment. PMID- 25132914 TI - Linking the Ohio Cancer Incidence Surveillance System with Medicare, Medicaid, and Clinical Data from Home Health Care and Long Term Care Assessment Instruments: Paving the Way for New Research Endeavors in Geriatric Oncology. AB - This study describes the Ohio Cancer-Aging Linked Database, which mirrors in structure the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare files, but also incorporates data from Medicaid enrollment and claims files, the home health care (HHC) Outcome Assessment Information Set (OASIS), and the long term care (LTC) Minimum Data Set (MDS). This article also discusses the potential uses of this database, particularly in addressing new research questions emerging from the nascent and rapidly developing field of geriatric oncology. PMID- 25132915 TI - SEGMENTATION OF MITOCHONDRIA IN ELECTRON MICROSCOPY IMAGES USING ALGEBRAIC CURVES. AB - High-resolution microscopy techniques have been used to generate large volumes of data with enough details for understanding the complex structure of the nervous system. However, automatic techniques are required to segment cells and intracellular structures in these multi-terabyte datasets and make anatomical analysis possible on a large scale. We propose a fully automated method that exploits both shape information and regional statistics to segment irregularly shaped intracellular structures such as mitochondria in electron microscopy (EM) images. The main idea is to use algebraic curves to extract shape features together with texture features from image patches. Then, these powerful features are used to learn a random forest classifier, which can predict mitochondria locations precisely. Finally, the algebraic curves together with regional information are used to segment the mitochondria at the predicted locations. We demonstrate that our method outperforms the state-of-the-art algorithms in segmentation of mitochondria in EM images. PMID- 25132913 TI - Expression of senescence-associated microRNAs and target genes in cellular aging and modulation by tocotrienol-rich fraction. AB - Emerging evidences highlight the implication of microRNAs as a posttranscriptional regulator in aging. Several senescence-associated microRNAs (SA-miRNAs) are found to be differentially expressed during cellular senescence. However, the role of dietary compounds on SA-miRNAs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on SA miRNAs (miR-20a, miR-24, miR-34a, miR-106a, and miR-449a) and established target genes of miR-34a (CCND1, CDK4, and SIRT1) during replicative senescence of human diploid fibroblasts (HDFs). Primary cultures of HDFs at young and senescent were incubated with TRF at 0.5 mg/mL. Taqman microRNA assay showed significant upregulation of miR-24 and miR-34a and downregulation of miR-20a and miR-449a in senescent HDFs (P < 0.05). TRF reduced miR-34a expression in senescent HDFs and increased miR-20a expression in young HDFs and increased miR-449a expression in both young and senescent HDFs. Our results also demonstrated that ectopic expression of miR-34a reduced the expression of CDK4 significantly (P < 0.05). TRF inhibited miR-34a expression thus relieved its inhibition on CDK4 gene expression. No significant change was observed on the expression of CCND1, SIRT1, and miR-34a upstream transcriptional regulator, TP53. In conclusion tocotrienol rich fraction prevented cellular senescence of human diploid fibroblasts via modulation of SA-miRNAs and target genes expression. PMID- 25132912 TI - New insights into the role of mitochondrial dynamics and autophagy during oxidative stress and aging in the heart. AB - The heart is highly sensitive to the aging process. In the elderly, the heart tends to become hypertrophic and fibrotic. Stiffness increases with ensuing systolic and diastolic dysfunction. Aging also affects the cardiac response to stress. At the molecular level, the aging process is associated with accumulation of damaged proteins and organelles, partially due to defects in protein quality control systems. The accumulation of dysfunctional and abnormal mitochondria is an important pathophysiological feature of the aging process, which is associated with excessive production of reactive oxygen species. Mitochondrial fusion and fission and mitochondrial autophagy are crucial mechanisms for maintaining mitochondrial function and preserving energy production. In particular, mitochondrial fission allows for selective segregation of damaged mitochondria, which are afterward eliminated by autophagy. Unfortunately, recent evidence indicates that mitochondrial dynamics and autophagy are progressively impaired over time, contributing to the aging process. This suggests that restoration of these mechanisms could delay organ senescence and prevent age-associated cardiac diseases. Here, we discuss the current understanding of the close relationship between mitochondrial dynamics, mitophagy, oxidative stress, and aging, with a particular focus on the heart. PMID- 25132917 TI - Endoscopic retrograde cholangiopancreatography in patients with altered anatomy: How to deal with the challenges? AB - Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is challenging. Several operative interventions of both the gastrointestinal tract and the biliary and/or pancreatic system lead to altered anatomy, rendering ERCP more difficult or even impossible with a conventional side-viewing duodenoscope. Adapted endoscopes are available to reach the biliopancreatic system and to perform ERCP in patients with altered anatomy. However, both technical difficulties and complications determine the procedure's success. Different technical approaches have been described and are highly dependent on local expertise and endoscopic equipment. Standardized practical guidelines are currently unavailable. This review focuses on the challenges encountered during ERCP in patients with altered anatomy and how to deal with them. The first challenge is reaching the papilla or the bilioenteric/pancreatoenteric anastomosis in the patient with postoperative altered anatomy. The second challenge is the cannulation of the biliopancreatic system and performing all conventional ERCP interventions and the third challenge is the control of possible complications. The available literature data on this topic is reviewed and illustrated with clinical cases. PMID- 25132916 TI - New aspects of modern endoscopy. AB - The prognosis for patients with malignancies of the gastrointestinal-tract is strictly dependent on early detection of premalignant and malignant lesions. However, small, flat or depressed neoplastic lesions remain difficult to detect with these technologies thereby limiting their value for polyp and cancer screening. At the same time computer and chip technologies have undergone major technological changes which have greatly improved endoscopic diagnostic investigation. New imaging modalities and techniques are very notable aspects of modern endoscopy. Chromoendoscopy or filter-aided colonoscopy (virtual chromoendoscopy) with high definition endoscopes is able to enhance the detection and characterization of lesions. Finally, confocal laser endomicroscopy provides histological confirmation of the presence of neoplastic changes. The developing techniques around colonoscopy such as the retro-viewing colonoscope, the balloon colonoscope or the 330-degrees-viewing colonoscope try to enhance the efficacy by reducing the adenoma miss rate in right-sided, non-polypoid lesions. Colon capsule endoscopy is limited to identifying cancer and not necessarily small adenomas. Preliminary attempts have been made to introduce this technique in clinical routine. PMID- 25132918 TI - Continued evidence for safety of endoscopic retrograde cholangiopancreatography during pregnancy. AB - AIM: To report the safety of continued use of endoscopic retrograde cholangiopancreatography (ERCP) during pregnancy at various maternal ages. METHODS: A retrospective chart review of pregnant patients who underwent ERCP at a tertiary academic center was undertaken between 2002 and 2012. Pertinent past medical history and initial presenting laboratory data were collected. Review of the procedure note for each ERCP performed provided documentation of lead shielding, type of sedation, fluoroscopy time, and post-procedure complications. Patients' clinical courses were reviewed until the time of delivery and pregnancy complications with fetal outcomes were examined. Data was stratified based upon the mother's age at the time of ERCP: 18-21, 22-29, and >= 30 years of age. RESULTS: Twenty pregnant patients who underwent ERCP between 2002 and 2012 were identified. The mean age at the time of ERCP was 26.4 years (18-38 years) and the average trimester was the second. The indications for ERCP were choledocholithiasis in 17 patients, gallstone pancreatitis in 2 patients, and cholangitis in 1 patient. The mean fluoroscopy time of ERCP was 3.8 min (0.3-23.6 min). Sphincterotomy was performed in 18 patients with therapeutic intent and not as a prophylactic measure to prevent recurrences. Clinical documentation of use of protective shielding was found in only 8 notes (40%). Post procedure complications were limited to two cases of post-ERCP pancreatitis (10%). Elective cholecystectomy was performed shortly after ERCP in 11 of the pregnant patients. Birth records were available for 16 patients, of which 15 had full-term pregnancies. Cesarean sections were performed in 5 (31%) patients. Term birth weight was greater than 2500 g in all cases except one in which the mother had a known hypercoagulable state. CONCLUSION: ERCP during pregnancy is both safe and efficacious regardless of maternal age or trimester. PMID- 25132919 TI - Virtual chromoendoscopy in small bowel capsule endoscopy: New light or a cast of shadow? AB - AIM: To evaluate whether virtual chromoendoscopy can improve the delineation of small bowel lesions previously detected by conventional white light small bowel capsule endoscopy (SBCE). METHODS: Retrospective single center study. One hundred lesions selected from forty-nine consecutive conventional white light SBCE (SBCE WL) examinations were included. Lesions were reviewed at three Flexible Spectral Imaging Color Enhancement (FICE) settings and Blue Filter (BF) by two gastroenterologists with experience in SBCE, blinded to each other's findings, who ranked the quality of delineation as better, equivalent or worse than conventional SBCE-WL. Inter-observer percentage of agreement was determined and analyzed with Fleiss Kappa (kappa) coefficient. Lesions selected for the study included angioectasias (n = 39), ulcers/erosions (n = 49) and villous edema/atrophy (n = 12). RESULTS: Overall, the delineation of lesions was improved in 77% of cases with FICE 1, 74% with FICE 2, 41% with FICE 3 and 39% with the BF, with a percentage of agreement between investigators of 89% (kappa = 0.833), 85% (kappa = 0.764), 66% (kappa = 0.486) and 79% (kappa = 0.593), respectively. FICE 1 improved the delineation of 97.4% of angioectasias, 63.3% of ulcers/erosions and 66.7% of villous edema/atrophy with a percentage of agreement of 97.4% (kappa = 0.910), 81.6% (kappa = 0.714) and 91.7% (kappa = 0.815), respectively. FICE 2 improved the delineation of 97.4% of angioectasias, 57.1% of ulcers/erosions and 66.7% of villous edema/atrophy, with a percentage of agreement of 89.7% (kappa = 0.802), 79,6% (kappa = 0.703) and 91.7% (kappa = 0.815), respectively. FICE 3 improved the delineation of 46.2% of angioectasias, 24.5% of ulcers/erosions and none of the cases of villous edema/atrophy, with a percentage of agreement of 53.8% [kappa = not available (NA)], 75.5% (kappa = NA) and 66.7% (kappa = 0.304), respectively. The BF improved the delineation of 15.4% of angioectasias, 61.2% of ulcers/erosions and 25% of villous edema/atrophy, with a percentage of agreement of 76.9% (kappa = 0.558), 81.6% (kappa = 0.570) and 25.0% (kappa = NA), respectively. CONCLUSION: Virtual chromoendoscopy can improve the delineation of angioectasias, ulcers/erosions and villous edema/atrophy detected by SBCE, with almost perfect interobserver agreement for FICE 1. PMID- 25132921 TI - Endoscopic ultrasound-guided drainage of pelvic abscess: A case series of 8 patients. AB - AIM: To show the safety and effectiveness of endoscopic ultrasound (EUS)-guided drainage of pelvic abscess that were inaccessible for percutaneous drainage. METHODS: Eight consecutive patients with pelvic abscess that were not amenable to drainage under computed tomography (CT) guidance were referred for EUS-guided drainage. The underlying cause of the abscesses included diverticulitis in 4, postsurgical surgical complications in 2, iatrogenic after enema in 1, and Crohn's disease in 1 patient. Abscesses were all drained under EUS guidance via a transrectal or transsigmoidal approach. RESULTS: EUS-guided placement of one or two 7 Fr pigtail stents was technically successful and uneventful in all 8 patients (100%). The abscess was perisigmoidal in 2 and was multilocular in 4 patients. All procedures were performed under conscious sedation and without fluoroscopic monitoring. Fluid samples were successfully retrieved for microbiological studies in all cases and antibiotic policy was adjusted according to culture results in 5 patients. Follow-up CT showed complete recovery and disappearance of abscess. The stents were retrieved by sigmoidoscopy in only two patients and had spontaneously migrated to outside in six patients. All drainage procedures resulted in a favourable clinical outcome. All patients became afebrile within 24 h after drainage and the mean duration of the postprocedure hospital stay was 8 d (range 4-14). Within a median follow up period of 38 mo (range 12-52) no recurrence was reported. CONCLUSION: We conclude that EUS-guided drainage of pelvic abscesses without fluoroscopic monitoring is a minimally invasive, safe and effective approach that should be considered in selected patients. PMID- 25132920 TI - Evaluation of diagnostic cytology via endoscopic naso-pancreatic drainage for pancreatic tumor. AB - AIM: To evaluate the usefulness of cytology of the pancreatic juice obtained via the endoscopic naso-pancreatic drainage tube (ENPD-C). METHODS: ENPD was performed in cases where a diagnosis could not be made other than by using endoscopic retrograde cholangiopancreatography and in cases of pancreatic neoplasms or cystic tumors, including intraductal papillary mucinous neoplasm (IPMN) suspected to have malignant potential. 35 patients (21 males and 14 females) underwent ENPD between January 2007 and June 2013. The pancreatic duct was imaged and the procedure continued in one of ENPD-C or ENPD-C plus brush cytology (ENPD-BC). We checked the cytology result and the final diagnosis. RESULTS: The mean patient age was 69 years (range, 48-86 years). ENPD-C was performed in 24 cases and ENPD-C plus brush cytology (ENPD-BC) in 11 cases. The ENPD tube was inserted for an average of 3.5 d. The final diagnosis was confirmed on the basis of the resected specimen in 18 cases and of follow-up findings at least 6 mo after ENPD in the 18 inoperable cases. Malignancy was diagnosed in 21 cases and 14 patients were diagnosed as having a benign condition. The ratios of class V/IV:III:II/I findings were 7:7:7 in malignant cases and 0:3:11 in benign cases. The sensitivity and specificity for all patients were 33.3% and 100%, respectively. The cytology-positive rate was 37.5% (6/16) for pancreatic cancer. For IPMN cases, the sensitivity and specificity were 33% and 100%, respectively. CONCLUSION: Sensitivity may be further increased by adding brush cytology. Although we can diagnosis cancer in cases of a positive result, the accuracy of ENPD-C remains unsatisfactory. PMID- 25132922 TI - Bowel preparation for colonoscopy using standard vs reduced doses of sodium phosphate: A single-blind randomized controlled study. AB - AIM: To evaluate the efficacy of a colonoscopy preparation that utilizes a reduced dose of sodium phosphate (NaP) and an adjunct. METHODS: Sixty-two patients requiring screening colonoscopies were studied. Each patient was randomly allocated to receive either 50 NaP tablets (50 g) or 30 NaP tablets (30 g) with 10 mL of 0.75% sodium picosulfate for bowel preparation. NaP was administered at a rate of five tablets (5 g) or three tablets (3 g) every 15 min with 200 mL of water, beginning five to six hours before colonoscopy. The sodium picosulfate was administered with 200 mL of water on the night before the procedure. Both groups were compared in term of the efficacies of colonic cleansing, the time required for completion of the bowel preparation, and acceptability of the preparation. RESULTS: Sixty patients (n = 30 for each group) were analyzed. The cleansing efficacy tended to be higher in the 30 g NaP plus sodium picosulfate group as assessed by the mean total Ottawa scale score (50 g NaP 6.70 +/- 1. 42 vs 30 g NaP plus sodium picosulfate 6.17 +/- 1.18 P = 0.072). The mean time for bowel preparation tended to be shorter in the 30 g NaP plus sodium picosulfate group (50 g NaP 189.9 +/- 64.0 min vs 30 g NaP plus sodium picosulfate 161.8 +/- 57.6 min, P = 0.065). There were no significant differences between the two groups in the acceptability of the preparations (50 g NaP 83.3% vs 30 g NaP plus sodium picosulfate 86.7%, P = 0.500). There were no adverse events related to bowel preparation in either of the groups. CONCLUSION: The colonoscopy preparation that utilized 30 g NaP with sodium picosulfate was comparable to that utilizing 50 g NaP. This novel bowel preparation might be useful before colonoscopy. PMID- 25132923 TI - Lymphoepithelioma-like esophageal carcinoma with macroscopic reduction. AB - Esophageal lymphoepithelioma-like carcinoma (LELC) is extremely rare. We report the first case of esophageal LELC showing macroscopic reduction. A 67-year-old male presented with dysphagia and, by endoscopic examination, was found to have a significantly raised tumor of 10 mm in diameter in the thoracic esophagus. The biopsied material showed esophageal cancer. We performed endoscopic submucosal dissection. However, the tumor became flattened, similar to a scar, in only 2 mo. Histologically, the carcinoma cells had infiltrated the submucosal layer. Prominent infiltration of T lymphoid cells that stained positive for CD8 was observed around the carcinoma cells. Therefore, this lesion was considered to be an LELC with poorly differentiated squamous cells. Because the margin was positive, an esophagectomy was performed. Carcinoma cells were detected in the neck in one lymph node. The staging was T1N0M1b. However, the patient has been well, without adjuvant therapy or recurrence, for more than 5 years. PMID- 25132924 TI - Esophageal cancer management controversies: Radiation oncology point of view. AB - Esophageal cancer treatment has evolved from single modality to trimodality therapy. There are some controversies of the role, target volumes and dose of radiotherapy (RT) in the literature over decades. The present review focuses primarily on RT as part of the treatment modalities, and highlight on the RT volume and its dose in the management of esophageal cancer. The randomized adjuvant chemoradiation (CRT) trial, intergroup trial (INT 0116) enrolled 559 patients with resected adenocarcinoma of the stomach or gastroesophageal junction. They were randomly assigned to surgery plus postoperative CRT or surgery alone. Analyses show robust treatment benefit of adjuvant CRT in most subsets for postoperative CRT. The Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) used a lower RT dose of 41.4 Gray in 23 fractions with newer chemotherapeutic agents carboplatin and paclitaxel to achieve an excellent result. Target volume of external beam radiation therapy and its coverage have been in debate for years among radiation oncologists. Pre operative and post-operative target volumes are designed to optimize for disease control. Esophageal brachytherapy is effective in the palliation of dysphagia, but should not be given concomitantly with chemotherapy or external beam RT. The role of brachytherapy in multimodality management requires further investigation. On-going studies of multidisciplinary treatment in locally advanced cancer include: ZTOG1201 trial (a phase II trial of neoadjuvant and adjuvant CRT) and QUINTETT (a phase III trial of neoadjuvant vs adjuvant therapy with quality of life analysis). These trials hopefully will shed more light on the future management of esophageal cancer. PMID- 25132925 TI - Endoscopic assessment and management of early esophageal adenocarcinoma. AB - Esophageal carcinoma affects more than 450000 people worldwide and the incidence is rapidly increasing. In the United States and Europe, esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence. Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages. Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett's esophagus. These risk factors include chronic gastroesophageal reflux disease, hiatal hernia, advanced age, male sex, white race, cigarette smoking, and obesity. The annual risk of esophageal cancer is approximately 0.25% for patients without dysplasia and 6% for patients with high-grade dysplasia. Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa. The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option. The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high grade dysplasia. Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation, photodynamic therapy and cryoablation. Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion. Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor, positive lymph node and submucosal invasion. Surgical resection should be offered to patients with deep submucosal invasion. PMID- 25132927 TI - Neuroendocrine tumors of the gastrointestinal tract: Case reports and literature review. AB - Neuroendocrine tumors (NET) previously called carcinoid tumors are neoplasms of enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity that may result in the carcinoid syndrome. The annual incidence of patients with NET is 8.4 per 100000; yet many NET remain asymptomatic and clinically undetected. A majority of NET follows a benign course; however, some will display malignant characteristics. NET most commonly occur in the gastrointestinal tract (67%) and bronchopulmonary system (25%). Gastrointestinal NET occur within the stomach, small intestine, liver, and rectum. We report a retrospective study of 11 subjects: Eight with benign carcinoid tumors: duodenal bulb (n = 2), terminal ileum (n = 1), sigmoid colon (n = 2), and rectum (n = 3); three with malignant carcinoid: liver (n = 1) and intra-abdominal site (n = 2). The diagnosis, endoscopic images, outcome, treatment and review of the literature are presented. PMID- 25132928 TI - Matrix Degradative Enzymes and Their Inhibitors during Annular Inflammation: Initial Step of Symptomatic Intervertebral Disc Degeneration. AB - OBJECTIVE: Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. METHODS: Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF) 1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. RESULTS: MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin 1beta stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP 2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. CONCLUSION: Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy. PMID- 25132926 TI - In vitro effects of polyphenols on colorectal cancer cells. AB - AIM: To investigate the effects of quercetin and genistein on colon cancer cell proliferation and their estrogen receptor beta (ERbeta) expression. METHODS: Colon cancer cells were stably transfected with a mammalian expression vector to overexpress ERbeta (HCT8-beta8-expressing cells) or a control vector (HCT8 pSV2neo-expressing cells). The proliferation of these cells was examined after treatment with quercetin or genistein (5-100 MUmol/L), or 10 nmol/L 17beta estradiol (17beta-E2). Cell viability was examined by acridine orange staining following treatments for 48 or 144 h. Effects of quercetin and genistein on ERbeta transcriptional transactivation were examined by luciferase activity in HCT8-beta8-expressing cells transiently transfected with a pEREtkLUC reporter vector. In addition, the regulation of ERbeta transcription by phytoestrogens and 17beta-E2 was examined by quantitative polymerase chain reaction. RESULTS: Proliferation of HCT8-beta8-expressing cells was not reduced low doses (5 MUmol/L) of quercetin and genistein, while it was reduced at 25-50 MUmol/L with an effect similar to 10 nmol/L 17beta-E2. Treatment with doses of phytoestrogens >= 75 MUmol/L completely blocked cell growth and reduced overall cell counts, however no effects at any dose were observed in HCT8-pSV2neo-expressing cells. These results were supported by viability staining that revealed acridine orange stained lysosomes with high doses or extended treatment periods. Genistein and quercetin (50 MUmol/L) significantly increased ER-responsive luciferase activity similar to 10 nmol/L 17beta-E2 (P < 0.05). Furthermore, genistein and quercetin (50 MUmol/L), as well as 10 nmol/L 17beta-E2 significantly increased ERbeta mRNA levels in HCT8-beta8-expressing cells (P < 0.05). In addition, treatment of HCT8 pSV2neo-expressing cells with 50 umol/L quercetin or 10 nmol/L 17beta-E2 significantly increased ERbeta mRNA levels compared to untreated controls (P < 0.05), though the absolute levels were much lower than in HCT8-beta8-expressing cells. CONCLUSION: The antitumorigenic effects of the phytoestrogenic compounds quercetin and genistein on colon cancers cells occur through ERbeta activity and expression. PMID- 25132929 TI - Microanatomy and histological features of central myelin in the root exit zone of facial nerve. AB - OBJECTIVE: The aim of this study was to evaluate the microanatomy and histological features of the central myelin in the root exit zone of facial nerve. METHODS: Forty facial nerves with brain stem were obtained from 20 formalin fixed cadavers. Among them 17 facial nerves were ruined during preparation and 23 root entry zone (REZ) of facial nerves could be examined. The length of medial REZ, from detach point of facial nerve at the brain stem to transitional area, and the thickness of glial membrane of central myelin was measured. We cut brain stem along the facial nerve and made a tissue block of facial nerve REZ. Each tissue block was embedded with paraffin and serially sectioned. Slices were stained with hematoxylin and eosin (H&E), periodic acid Schiff, and glial fibrillary acid protein. Microscopy was used to measure the extent of central myelin and thickness of outer glial membrane of central myelin. Thickness of glial membrane was examined at two different points, the thickest area of proximal and distal REZ. RESULTS: Special stain with PAS and GFAP could be differentiated the central and peripheral myelin of facial nerve. The length of medial REZ was mean 2.6 mm (1.6-3.5 mm). The glial limiting membrane of brain stem is continued to the end of central myelin. We called it glial sheath of REZ. The thickness of glial sheath was mean 66.5 um (40-110 um) at proximal REZ and 7.4 um (5-10 um) at distal REZ. CONCLUSION: Medial REZ of facial nerve is mean 2.6 mm in length and covered by glial sheath continued from glial limiting membrane of brain stem. Glial sheath of central myelin tends to become thin toward transitional zone. PMID- 25132930 TI - Direct lateral lumbar interbody fusion: clinical and radiological outcomes. AB - OBJECTIVE: According to the recent development of minimally invasive spinal surgery, direct lumbar interbody fusion (DLIF) was introduced as an effective option to treat lumbar degenerative diseases. However, comprehensive results of DLIF have not been reported in Korea yet. The object of this study is to summarize radiological and clinical outcomes of our DLIF experience. METHODS: We performed DLIF for 130 patients from May 2011 to June 2013. Among them, 90 patients, who could be followed up for more than 6 months, were analyzed retrospectively. Clinical outcomes were compared using visual analog scale (VAS) score and Oswestry Disability Index (ODI). Bilateral foramen areas, disc height, segmental coronal and sagittal angle, and regional sagittal angle were measured. Additionally, fusion rate was assessed. RESULTS: A total of 90 patients, 116 levels, were underwent DLIF. The VAS and ODI improved statistically significant after surgery. All the approaches for DLIF were done on the left side. The left and right side foramen area changed from 99.5 mm(2) and 102.9 mm(2) to 159.2 mm(2) and 151.2 mm(2) postoperatively (p<0.001). Pre- and postoperative segmental coronal and sagittal angles changed statistically significant from 4.1 degrees and 9.9 degrees to 1.1 degrees and 11.1 degrees . Fusion rates of 6 and 12 months were 60.9% and 87.8%. Complications occurred in 17 patients (18.9%). However, most of the complications were resolved within 2 months. CONCLUSION: DLIF is not only effective for indirect decompression and deformity correction but also shows satisfactory mechanical stability and fusion rate. PMID- 25132931 TI - Comparison of outcomes after atlantoaxial fusion with transarticular screws and screw-rod constructs. AB - OBJECTIVE: The purpose of this study was to compare the radiological and neurological outcomes between two atlantoaxial fusion method for atlantoaxial stabilization; C1 lateral mass-C2 pedicle screws (screw-rod constructs, SRC) versus C1-2 transarticular screws (TAS). METHODS: Forty-one patients in whom atlantoaxial instability was treated with atlantoaxial fixation by SRC group (27 patients, from March 2005 to May 2011) or TAS group (14 patients, from May 2000 to December 2005) were retrospectively reviewed. Numeric rating scale (NRS) for pain assessment, Oswestry disability index (ODI), and Frankel grade were also checked for neurological outcome. In radiologic outcome assessment, proper screw position and fusion rate were checked. Perioperative parameters such as blood loss during operation, operation time, and radiation exposure time were also reviewed. RESULTS: The improvement of NRS and ODI were not different between both groups significantly. Good to excellent response in Frankel grade is shown similarly in both groups. Proper screw position and fusion rate were also observed similarly between two groups. Total bleeding amount during operation is lesser in SRC group than TAS group, but not significantly (p=0.06). Operation time and X-ray exposure time were shorter in SRC group than in TAS group (all p<0.001). CONCLUSION: Both TAS and SRC could be selected as safe and effective treatment options for C1-2 instability. But the perioperative result, which is technical demanding and X-ray exposure might be expected better in SRC group compared to TAS group. PMID- 25132932 TI - A morphometric study of the lumbar interspinous space in 100 stanford university medical center patients. AB - OBJECTIVE: With the increased use of interspinous spacers in the treatment of lumbar stenosis, knowledge of the geometry of the interspinous space is important. To prevent dislodgment of an interspinous spacer, the accurate depth and width of the interspinous space needs to be established to facilitate the best intraoperative selection of correct spacer size. METHODS: To determine the depth and width of the interspinous space, two methods are available which utilize plain film and magnetic resonance imaging (MRI). Data analysis of the interspinous depth and width was undertaken in 100 patients. RESULTS: The standard deviations were variable, since skin thickness (zone 1) was altered by sex and age. The difference in the zone 1 distance between adjacent interspinous processes varied according to gender (p<0.05), but was not influenced by age [p=0.32 by analysis of variance between groups (ANOVA)]. Zone 2, the supraspinous, and zone 3, the interspinous ligament depths, comprise the operative working area during insertion of an interspinous spacer. There were no differences with regard to gender or age (p>0.05). For zones 6 and 7, the interspinous distances at the narrowest and widest points, respectively, were found to decrease with the aging process, but the decrease was not statistically significant. There were no differences with regard to gender (p>0.05). CONCLUSION: This study provides additional information on the interspinous space. This statistical data are valuable for use in the design of interspinous spacers. PMID- 25132933 TI - Preoperative weakness and demyelination of the corticospinal tract in meningioma patients : changes in diffusion parameters using diffusion tensor imaging. AB - OBJECTIVE: Differentiation of demyelination in white matter from axonal damage can be determined using diffusion tensor imaging (DTI). In this study using meningioma patients an attempt was made to evaluate the relationship between preoperative weakness and the changes of diffusion parameters in the corticospinal tract (CST) using DTI. METHODS: Twenty-six patients with meningioma were enrolled in this study. Eleven of them suffered from objective motor weakness and were classified as Group 1. The remaining 15 patients did not present motor weakness and were classified as Group 2. Fiber tractography and CST diffusion parameters were obtained using DTIStudio. The ratios (lesion side mean value/contralateral side mean value) of CST diffusion parameters were compared with 1.0 as a test value using a one-sample t-test. RESULTS: In Group 1, fractional anisotropy (FA), tensor trace (TT), and radial diffusivity (RD, lambda2 and lambda3) of the CST were significantly different between two hemispheres, but axial diffusivity (AD, lambda1) of the CST was not significantly different between two hemispheres. In Group 2, FA and lambda3 of CST did not differ significantly between the hemispheres. In Group 2, TT, lambda1, and lambda2 of CST in the ipsilateral hemisphere were significantly higher than those of the unaffected hemisphere. However, the differences were small. CONCLUSION: Motor weakness was related to a low FA and high TT resulting from increased RD of the CST fibers. CST diffusion changes in patients with weakness are similar to those for demyelination. PMID- 25132934 TI - Endovascular Treatment of a Ruptured Posterior Inferior Cerebellar Artery Aneurysm during Pregnancy. AB - Aneurysmal subarachnoid hemorrhage (SAH) during pregnancy is quite rare, however it has a high maternal mortality rate. A pregnant woman in the 16th gestational week was admitted to our hospital with a drowsy level of consciousness. A brain magnetic resonance (MR) image showed hemorrhage on the prepontine cistern, and both sylvian fissures, and MR angiography and cerebral digital subtraction angiography demonstrated an aneurysm at the left posterior inferior cerebellar artery (PICA). We performed endovascular coil embolization attempting to minimize radiation exposure. She was discharged with no neurologic deficit and delivered a healthy baby by cesarean section at the 38th week of gestation. This case study reported the shortest gestational period and this is the first report on an aneurysmal rupture arising from PICA which was treated using an endovascular method. Using an appropriate technique for reduced radiation exposure to the fetus and limited alterations in maternal-fetal physiology, endovascular coil embolization could guarantee good results in treatment of aneurysmal SAH in pregnant women. PMID- 25132935 TI - Acute Onset of Intracerebral Hemorrhage due to Autonomic Dysreflexia. AB - Autonomic dysreflexia is a clinical emergency syndrome of uncontrolled sympathetic output that can occur in patients who have a history of spinal cord injury. Despite its frequency in spinal cord injury patients, central nervous system complications are very rare. We report a man with traumatic high level incomplete spinal cord injury who suffered hypertensive right thalamic hemorrhage secondary to an episode of autonomic dysreflexia. Prompt recognition and removal of the triggering factor, the suprapubic catheter obstruction which led to hypertensive attack, the patient had a favorable functional outcome after the resorption of the hematoma and effective rehabilitation programme. PMID- 25132936 TI - Thrombosis and recanalization of small saccular cerebral aneurysm : two case reports and a suggestion for possible mechanism. AB - Reports of thrombosis and recanalization of cerebral aneurysm are rare. We report two cases of small, saccular aneurysms in which spontaneous thrombosis had occurred during the preparation for endovascular coiling. Also, we review reported cases and propose the presumed pathogenesis. PMID- 25132937 TI - A morphologically atypical case of atlantoaxial rotatory subluxation. AB - A rare case of atlantoaxial rotatory subluxation occurred after pediatric cervical spine surgery performed to remove a dumbbell-shaped meningioma at the level of the C1/C2 vertebrae. This case is classified as a post-surgical atlantoaxial rotatory subluxation, but has a very rare morphology that has not previously been reported. Although there are several reports about post-surgical atlantoaxial rotatory subluxation, an important point of this case is that it might be directly related to the spinal cord surgery in C1/C2 level. On day 6 after surgery, the patient presented with the Cock Robin position, and a computed tomography scan revealed a normal type of atlantoaxial rotatory subluxation. Manual reduction was performed followed by external fixation with a neck collar. About 7 months after the first surgery, the subluxation became severe, irreducible, and assumed an atypical form where the anterior tubercle of C1 migrated to a cranial position, and the posterior tubercle of C1 and the occipital bone leaned in a caudal direction. The pathogenic process suggested deformity of the occipital condyle and bilateral C2 superior facets with atlantooccipital subluxation. A second operation for reduction and fixation was performed, and the subluxation was stabilized by posterior fixation. We encountered an unusual case of a refractory subluxation that was associated with an atypical deformity of the upper spine. The case was successfully managed by posterior fixation. PMID- 25132938 TI - Management of traumatic c6-7 spondyloptosis with cord compression. AB - A case of total spondyloptosis of the cervical spine at C6-7 level with cord compression is described in a 51-year-old male. Because the bodies of C6 and 7 were tightly locked together, cervical traction failed. Then the patient was operated on by a posterior approach. Posterior stabilization and fusion were performed by C4-5 lateral mass and C7-T1 pedicle screw fixation and rod instrumentation with bridging both C4-5's rods to the C7-T1's extended ones. After C6 total laminectomy and foraminotomy, the C6 body was returned to its proper position. Secondly, anterior stabilization and fusion were performed by C6 7 discectomy with a screw-plate system. A postoperative lateral plain radiograph showed good realignment. In this case, we report the clinical presentation and discuss the surgical modalities of C6-7 total spondyloptosis and the failed close reduction. PMID- 25132939 TI - Post-traumatic cerebral infarction following low-energy penetrating craniocerebral injury caused by a nail. AB - Post-traumatic cerebral infarction (PTCI) is a secondary insult which causes global cerebral hypoxia or hypoperfusion after traumatic brain injury, and carries a remarkable high mortality rate. PTCI is usually caused by blunt brain injury with gross hematoma and/or brain herniation. Herein, we present the case of a 91-year-old male who had sustained PTCI following a low-energy penetrating craniocerebral injury due to a nail without evidence of hematoma. The patient survived after a decompressive craniectomy, but permanent neurological damage occurred. This is the first case of profound PTCI following a low-energy penetrating craniocerebral nail injury and reminds clinicians of possibility this rare dreadful complication for care of head-injured patients. PMID- 25132940 TI - Early surgical treatment of pronator teres syndrome. AB - We report a rare case of pronator teres syndrome in a young female patient. She reported that her right hand grip had weakened and development of tingling sensation in the first-third fingers two months previous. Thenar muscle atrophy was prominent, and hypoesthesia was also examined on median nerve territory. The pronation test and Tinel sign on the proximal forearm were positive. Severe pinch grip power weakness and production of a weak "OK" sign were also noted. Routine electromyography and nerve conduction velocity showed incomplete median neuropathy above the elbow level with severe axonal loss. Surgical treatment was performed because spontaneous recovery was not seen one month later. PMID- 25132941 TI - IgG4-Related Intracranial Hypertrophic Pachymeningitis : A Case Report and Review of the Literature. AB - Hypertrophic pachymeningitis is an uncommon disorder that causes a localized or diffuse thickening of the dura mater. Recently, the possibility that IgG4-related sclerosing disease may underlie some cases of intracranial hypertrophic pachymeningitis has been suggested. We herein report the tenth case of IgG4 related intracranial hypertrophic pachymeningitis and review the previous literature. A 45-year-old male presented with left-sided focal seizures with generalization. Magnetic resonance imaging (MRI) revealed a diffuse thickening and enhancement of the right convexity dura matter and falx with focal nodularity. The surgically resected specimens exhibited the proliferation of fibroblast-like spindle cells and an infiltration of mononuclear cells, including predominantly plasma cells. The ratio of IgG4-positive plasma cells to the overall IgG-positive cells was 45% in the area containing the highest infiltration of plasma cells. On the basis of the above findings, IgG4-related sclerosing disease arising from the dura mater was suspected. IgG4-related sclerosing disease should be added to the pachymeningitis spectrum. PMID- 25132942 TI - Current status of robot-assisted laparoscopic surgery in pediatric urology. AB - Laparoscopic procedures for urological diseases in children have been proven to be safe and effective. However, the availability of laparoscopic procedures is still partly limited to experienced, high-volume centers because the procedures are technically demanding. The da Vinci robot system is being used for an increasing variety of reconstructive procedures because of the advantages of this approach, such as motion scaling, greater optical magnification, stereoscopic vision, increased instrument tip dexterity, and tremor filtration. Particularly in pediatric urologic surgery, where the operational field is limited owing to the small abdominal cavity of children, robotic surgical technology has its own strengths. Currently, robots are used to perform most surgeries in children that can be performed laparoscopically. In this review, we aimed to provide a comprehensive overview of the current role of robot-assisted laparoscopic surgery in Pediatric Urology by analyzing the published data in this field. A growing body of evidence supports the view that robotic technology is technically feasible and safe in pediatric urological surgery. Robotic technology provides additional benefits for performing reconstructive urologic surgery, such as in pyeloplasty, ureteral reimplantation, and enterocystoplasty procedures. The main limitations to robotic surgery are its high purchase and maintenance costs and that the cost-effectiveness of this technology remains to be validated. PMID- 25132943 TI - Associations between presenting symptoms, clinicopathological parameters, and prognosis in a contemporary series of patients with renal cell carcinoma. AB - PURPOSE: To evaluate the impact of presenting symptoms on survival in a contemporary series of patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: We prospectively recorded data on the presenting symptoms, pathology, and RCC-specific survival of 633 consecutive RCC patients who underwent surgery between 2003 and 2012. RESULTS: Four hundred thirty-three RCCs (68%) were incidental, 111 (18%) were associated with local symptoms, and 89 (14%) were associated with systemic symptoms. Among those with incidental RCC, 317 patients (73%) were completely asymptomatic and 116 patients (27%) presented with symptoms not related to the tumor. During a median follow-up interval of 40 months (interquartile range: 39 to 69 months), 77 patients died from RCC. In univariate analyses, symptom classification was significantly associated with RCC-specific survival (p<0.001). Patients with incidental RCC and unrelated symptoms tended to have worse prognosis than did patients who were completely asymptomatic, although this difference was not statistically significant (p=0.057). The symptom classification was associated with advanced TNM stages (p<0.001) and grade (p<0.001). CONCLUSIONS: This study confirms that presenting symptoms are associated with tumor characteristics and survival. The majority of RCCs are diagnosed incidentally in patients without any symptoms or with symptoms not related to RCC. Patients in the latter group tend to have a worse prognosis than do patients who are completely asymptomatic. With the increasing number of incidentally diagnosed RCCs, substratification of patients with incidental tumors may be prognostically relevant. PMID- 25132944 TI - Should we place ureteral stents in retroperitoneal laparoscopic ureterolithotomy?: Consideration of surgical techniques and complications. AB - PURPOSE: There is some debate over the necessity of ureteral stenting after laparoscopic ureterolithotomy. We evaluated the need for ureteral stenting after retroperitoneal laparoscopic ureterolithotomy (RLU). MATERIALS AND METHODS: Between January 2009 and January 2013, 41 patients underwent RLU to remove upper ureteral stones. The retroperitoneal approach was used in all patients by a single surgeon. A double J (D-J) stent was placed in the first 17 patients after the procedure but not in any of the next 24 patients. RESULTS: The mean patient age, serum creatinine levels, and stone size were not significantly different between the two groups. The stone-free rate was 100%. The mean operative time was significantly shorter in the stentless group than in the stent group (59.48 minutes vs. 77.88 minutes, p<0.001). Parenteral analgesic use and anticholinergic medication use were observed in the stent group only. The blood loss, drain removal day, and hospital stay were not significantly different between the two groups. No other significant complications occurred during or after the operation in any patients. CONCLUSIONS: RLU is a safe and effective treatment modality for large impacted ureteral stones. In this study, D-J stent placement was not necessary after RLU. In the future, large-scale studies of RLU without D-J stenting, especially on the frequency of the development of complications according to the surgical technique, may be needed. PMID- 25132945 TI - Multimodal treatments of cystine stones: an observational, retrospective single center analysis of 14 cases. AB - PURPOSE: To document the experiences of a single institution in evaluating the clinical courses and treatment outcomes of patients with cystine stones. MATERIALS AND METHODS: The clinical data of 14 patients with cystine stones who were treated at our institution from March 1994 to July 2012 were reviewed. These data included age at first visit, gender, family history, body mass index, presence of a single kidney, stone locations, stone burden, routine urinalysis, and culture. In addition, we also analyzed data on surgery, shock wave lithotripsy, medical treatment, stone recurrence or regrowth, and overall treatment success rates. RESULTS: The mean age of our patients at their first visit was 19.6+/-5.0 years, and eight patients were males. The median stone burden and mean urine pH before each surgery were 6.5 cm(2) and 6.5+/-0.9, respectively. Two patients had a family history of cystine stones. Patients underwent surgery an average of 2.7 times. The median interval between surgeries was 27.3 months, and 1 open surgery, 12 percutaneous nephrolithotomies, and 25 ureterorenoscopies were performed. Potassium citrate or sodium bicarbonate was used in nine cases. D-Penicillamine was continuously used in three patients. Patients had an average incidence of 3.2 recurrences or regrowth of stones during the median follow-up period of 60.5 months. CONCLUSIONS: Patients with cystine stones have high recurrence or regrowth rates and relatively large stone burdens. Adequate treatment schedules must therefore be established in these cases to prevent possible deterioration of renal function. PMID- 25132946 TI - Impact of transobturator tape treatment on overactive bladder symptoms, particularly nocturia, in patients with mixed urinary incontinence. AB - PURPOSE: We assessed the impact of transobturator tape (TOT) treatment on overactive bladder (OAB) symptoms with a particular focus on nocturia in patients with mixed urinary incontinence (MUI). MATERIALS AND METHODS: In this retrospective cohort study, the medical records of 237 women who underwent TOT surgery for the treatment of MUI were reviewed. Of these, 86 patients (36.4%) had preoperative nocturia. Patients with neurological diseases or sleep disorders that could affect the voiding pattern were excluded. Patients who were being treated with anticholinergics and antidiuretic hormones were also excluded, which left 70 subjects eligible for analysis. Pre- and postoperative evaluations consisted of a physical examination, 3-day frequency-volume chart, and health related quality of life questionnaires (King's health questionnaire, overactive bladder symptom score, and OAB-questionnaire). RESULTS: TOT treatment resulted in an overall significant improvement in OAB symptoms including nocturia. Frequency volume charts revealed that TOT treatment significantly decreased the actual number of nightly voids (ANV) and the nocturnal bladder capacity index (NBCi) in the entire cohort. However, in a subgroup of women with nocturnal polyuria, there was no significant change in ANV or NBCi after the sling operation. Correlation analysis of the whole cohort revealed that the postoperative changes in NBCi correlated positively with postoperative changes in ANV. The nocturia-persisting group was more likely to have nocturnal polyuria and lower preoperative functional bladder capacity compared with the nocturia-improved group (p=0.024 and p=0.023, respectively). CONCLUSIONS: Our results demonstrated that the TOT procedure resulted in an overall significant improvement in OAB symptoms including OAB-related nocturia in patients who presented with MUI. PMID- 25132947 TI - Effect of histological inflammation on total and free serum prostate-specific antigen values in patients without clinically detectable prostate cancer. AB - PURPOSE: We are often confronted with patients in the "gray zone" (prostate specific antigen [PSA]<10 ng/mL) whose biopsies reveal no malignancy but only inflammation. We investigated the relationship between histological inflammation and total PSA (tPSA), free PSA (fPSA), and percentage of free PSA (f/tPSA) levels in patients without prostate cancer (PC). MATERIALS AND METHODS: We studied 106 men with tPSA<10 ng/mL who had undergone biopsy that was negative for PC and who had no clinical prostatitis. Inflammation observed at biopsies was scored for inflammation type in each biopsy core by use of a four-point scale and was then correlated with tPSA, fPSA, and f/tPSA. RESULTS: Different patterns of inflammation were found in each set of biopsies. Regression factor analysis was used to form two groups according to inflammation type: more chronic and more acute. Median tPSA, fPSA, and f/tPSA levels in the more chronic and more acute inflammation groups were 6.4 ng/mL, 1.09 ng/mL, and 15%, and 7.3 ng/mL, 0.79 ng/mL, and l2%, respectively. A significant difference was found in fPSA (p=0.003) and f/tPSA (p<0.001), whereas the difference in tPSA was not significant (p=0.200). Total PSA correlated with fPSA (r=0.4, p<0.001) but not with inflammation type (r=0.12, p>0.010). A correlation existed between inflammation type and fPSA (r=-0.31, p=0.001) and f/tPSA (r=-0.43, p<0.001) in that the fPSA and f/tPSA were lower in the group with more acute inflammation. CONCLUSIONS: Subclinical inflammation has a significant influence on fPSA in patients with tPSA<10 ng/mL but without PC or clinical prostatitis. Subclinical inflammation is not characterized by elevated tPSA alone but also by a decreased fPSA, a tendency similar to that in PC. PMID- 25132948 TI - Adolescent varicocele: are somatometric parameters a cause? AB - PURPOSE: It has been reported that varicocele is found less frequently in obese men. Accordingly, we evaluated varicocele patients and statistically analyzed the correlation between varicocele and somatometric parameters. MATERIALS AND METHODS: A total of 211 patients underwent surgery for varicoceles. All patients underwent history taking, physical examination, and scrotal ultrasound to determine the presence and severity of varicocele. An age-matched control group consisted of 102 patients who were found not to have varicocele according to physical examinations and scrotal ultrasound. The age, weight, height, and body mass index (BMI) of the two groups were compared. The statistical analyses were performed by use of PASW Statistics ver. 18.0. A p-value of less than 0.05 was used for statistical significance. RESULTS: In the varicocele group, the mean age, height, weight, and BMI were 29.42+/-14.01 years, 168.53+/-9.97 cm, 62.14+/ 13.17 kg, and 21.66+/-3.21 kg/m(2), respectively. The distribution of varicocele grade was as follows: 103 (48.8%) grade III, 72 (34.1%) grade II, and 36 (17.1%) grade I. In the control group, the mean age, height, weight, and BMI were 30.83+/ 17.31 years, 161.93+/-19.83 cm, 64.69+/-17.86 kg, and 24.04+/-3.64 kg/m(2), respectively. Analyzing these data specifically in adolescents, they showed significant differences in age, height, and BMI (p=0.000, p=0.000, and p=0.004, respectively) between two groups. There were no significant differences in somatometric parameters between patients with different grades of varicocele. CONCLUSIONS: Our results showed that patients with varicoceles were significantly taller and had a lower BMI than did patients without varicoceles, especially among adolescents. Carefully designed future studies may be needed. PMID- 25132949 TI - Are clinical, laboratory, and imaging markers suitable predictors of vesicoureteral reflux in children with their first febrile urinary tract infection? AB - PURPOSE: This study was conducted to determine the predictive value of clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in children with their first febrile urinary tract infection. MATERIALS AND METHODS: One hundred fifty-three children with their first febrile urinary tract infection were divided into two groups according to the results of voiding cystourethrography: 60 children with vesicoureteral reflux and 93 children without. The sensitivity, specificity, positive and negative predictive value, likelihood ratio (positive and negative), and accuracy of the clinical, laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were determined. RESULTS: Of the 153 children with febrile urinary tract infection, 60 patients (39.2%) had vesicoureteral reflux. There were significant differences between the two groups regarding fever>38C, suprapubic pain, C-reactive protein quantitative level, number of red blood cells in the urine, and results of renal ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were significant positive correlations between fever>38.2C and dimercaptosuccinic acid renal scanning and vesicoureteral reflux. Also, there were significant positive correlations between the erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux. CONCLUSIONS: This study revealed fever>38.2C and dimercaptosuccinic acid renal scanning as the best predictive markers for vesicoureteral reflux in children with their first febrile urinary tract infection. In addition, erythrocyte sedimentation rate, positive urinary nitrite test, hyaline cast, and renal ultrasound are the best predictive markers for high-grade vesicoureteral reflux. PMID- 25132950 TI - Altered gene expression profile after exposure to transforming growth factor beta1 in the 253J human bladder cancer cell line. AB - PURPOSE: Transforming growth factor beta1 (TGF-beta1) inhibits the growth of bladder cancer cells and this effect is prominent and constant in 253J bladder cancer cells. We performed a microarray analysis to search for genes that were altered after TGF-beta1 treatment to understand the growth inhibitory action of TGF-beta1. MATERIALS AND METHODS: 253J bladder cancer cells were exposed to TGF beta1 and total RNA was extracted at 6, 24, and 48 hours after exposure. The RNA was hybridized onto a human 22K oligonucleotide microarray and the data were analyzed by using GeneSpring 7.1. RESULTS: In the microarray analysis, a total of 1,974 genes showing changes of more than 2.0 fold were selected. The selected genes were further subdivided into five highly cohesive clusters with high probability according to the time-dependent expression pattern. A total of 310 genes showing changes of more than 2.0 fold in repeated arrays were identified by use of simple t-tests. Of these genes, those having a known function were listed according to clusters. Microarray analysis showed increased expression of molecules known to be related to Smad-dependent signal transduction, such as SARA and Smad4, and also those known to be related to the mitogen-activated protein kinase (MAPK) pathway, such as MAPKK1 and MAPKK4. CONCLUSIONS: A list of genes showing significantly altered expression profiles after TGF-beta1 treatment was made according to five highly cohesive clusters. The data suggest that the growth inhibitory effect of TGF-beta1 in bladder cancer may occur through the Smad dependent pathway, possibly via activation of the extracellular signal-related kinase 1 and Jun amino-terminal kinases Mitogen-activated protein kinase pathway. PMID- 25132952 TI - Management of an iatrogenic injury in a crossed ectopic kidney without fusion. AB - Crossed renal ectopia is a condition in which a kidney is located on the side opposite of its ureteral insertion. Ninety percent of crossed ectopic kidneys are fused to their ipsilateral uncrossed renal unit. Crossed renal ectopia without fusion is rare, with only 62 patients reported in the literature to date. These kidneys may suffer iatrogenic injury during an unrelated surgical intervention. The injury, unless self-limiting, may necessitate the removal of the ectopic kidney. We present a unique case of a dual injury, renal as well as ureteric, in a crossed ectopic kidney without fusion that was successfully managed without surgical excision. PMID- 25132951 TI - Adrenal cortical scintigraphy for lateralization of bilateral adrenal nodules in primary aldosteronism. PMID- 25132953 TI - Evaluating the impacts of stressors of Pseudomonas syringae pathovar tomato on the effectiveness of multi-locus variable number tandem repeat analysis and multi locus sequence typing in microbial forensic investigations. AB - BACKGROUND: Crops in the USA are vulnerable to natural and criminal threats because of their widespread cultivation and lack of surveillance, and because of implementation of growing practices such as monoculture. To prepare for investigation and attribution of such events, forensic assays, including determination of molecular profiles, are being adapted for use with plant pathogens. The use of multi-locus variable number tandem repeat (VNTR) analysis (MLVA) and multi-locus sequence typing (MLST) in investigations involving plant pathogens may be problematic because the long lag periods between pathogen introduction and discovery of associated disease may provide enough time for evolution to occur in the regions of the genome employed in each assay. Thus, more information on the stability of the loci employed in these methods is needed. RESULTS: The MLVA fingerprints and MLST profiles were consistent throughout the experiment, indicating that, using a specific set of primers and conditions, MLVA and MLST typing systems reliably identify P.s. tomato DC3000. This information is essential to forensic investigators in interpreting comparisons between MLVA and MLST typing profiles observed in P.s. tomato isolates. CONCLUSIONS: Our results indicate that MLVA and MLST typing systems, utilizing the specified primers and conditions, could be employed successfully in forensics investigations involving P.s. tomato. Similar experiments should be conducted in the field and with other high-consequence plant pathogens to ensure that the assays are reliable for pathogens infecting plants in their natural environment and for organisms that may display faster rates of mutation. PMID- 25132954 TI - Study design considerations for evaluating the efficacy and safety of pancreatic enzyme replacement therapy in patients with cystic fibrosis. AB - In 2006, the US FDA issued a 'Guidance for Industry' regarding submission of New Drug Applications for pancreatic enzyme replacement therapy (PERT) products. Five oral delayed-release PERT products have been approved by the FDA, and several others are under development and/ or evaluation for New Drug Application submission. We present in this paper recommendations of the Cystic Fibrosis Foundation's Cystic Fibrosis (CF) Therapeutics Development Network and Data Safety Monitoring Board regarding study design considerations for evaluating PERT products in patients with CF. Careful attention to study design and accuracy of the outcome measures has confirmed our understanding of the efficacy and safety of PERT for the treatment of exocrine pancreatic insufficiency of CF. PMID- 25132955 TI - Characterization and assessment of the sensitivity and resistance of a newly established human gastrointestinal stromal tumour xenograft model to treatment with tyrosine kinase inhibitors. AB - BACKGROUND: Acquired resistance to tyrosine kinase inhibitors (TKIs) in gastrointestinal stromal tumours (GISTs) is most commonly caused by secondary KIT or PDGFRA mutations. In this study we characterize a newly established GIST xenograft model, UZLX-GIST9, and evaluate the in vivo response of the model to standard TKIs (imatinib, sunitinib, and regorafenib). METHODS: Tumour fragments from a metastatic lesion of a GIST patient clinically progressing after treatment with imatinib, sunitinib and regorafenib were engrafted in a nude, immunodeficient mouse. Upon sequential passaging from mouse to mouse, tumour fragments were collected for histopathological and molecular characterization. The sensitivity of the model to treatment with TKIs was evaluated in 28 mice [passage 2 (n = 8), passage 4 (n = 20), 41 tumours]. Mice were grouped as follows: control (untreated), imatinib (50 mg/kg/BID), imatinib (100 mg/kg/BID), sunitinib (40 mg/kg/QD), and regorafenib (30 mg/kg/QD). After three weeks of oral treatment, tumours were collected for subsequent analysis. The efficacy of treatment was assessed by tumour volume, histopathology and Western immunoblotting. RESULTS: UZLX-GIST9 maintains the same typical morphological features and immunohistochemical characteristics as the original patient biopsy and expresses CD117 and DOG1. The KIT mutational profile (p.P577del + W557LfsX5+ D820G) remains the same as the original tissue sample originating from an intraspinal metastatic site. Three week treatment with different TKIs showed that the model is resistant to imatinib. Sunitinib induces tumour growth delay and regorafenib reduces the tumour burden by 30% as compared to control animals. While none of the TKIs had a significant effect on cell proliferation or cell survival, a remarkable increase of necrosis and significant reduction of microvessel density was observed under sunitinib and regorafenib. Western immunoblotting showed a mild reduction in KIT and AKT activation only in regorafenib treated tumours. CONCLUSIONS: We established a novel human GIST xenograft, UZLX-GIST9, harbouring KIT exon 11 and 17 mutations and maintaining the pheno-and genotype of the original tumour. UZLX-GIST9 shows different levels of response to standard TKIs. This model will help to study TKI resistance and to explore novel treatment approaches for patients with TKI-resistant GIST. PMID- 25132957 TI - Systemic fungal infection in a dog: a unique case in Ireland. AB - A three year old male entire Staffordshire bull terrier was referred to University College Dublin Veterinary Hospital, with a two week history of fever, inflammation of the right hock, lameness on the right hindlimb, peripheral lymphadenopathy and gastrointestinal signs (vomiting and diarrhoea). For the preceding three months the dog had been treated for atopic dermatitis with oral ciclosporin (5 mg/kg, PO, q 24 hours). Cytological analysis of the affected lymph nodes demonstrated fungal-like organisms predominantly contained within macrophages. Subsequent fungal culture and microscopic identification confirmed the presence of a Byssochlamys sp. This fungus is a saprophytic organism which has been associated with mycotoxin production. It has not previously been identified as a cause of systemic infection in animals or humans. Ciclosporin was discontinued, and a second generation triazole, voriconazole prescribed at a dose of 6 mg/kg for the first two doses, and continued at 3 mg/kg every 12 hours for six months. There was an excellent response. Follow-up examination five weeks after treatment was completed confirmed remission of the disease. The dog remains alive and well three years later. The present case represents an unusual fungal infection in a dog secondary to immunosuppressive therapy with ciclosporin. Such a possibility should be considered in animals presenting with signs consistent with systemic infection when receiving immunosuppressive medication. PMID- 25132956 TI - Hyperbaric oxygen therapy fails to reduce hydrocephalus formation following subarachnoid hemorrhage in rats. AB - BACKGROUND & PURPOSE: Approximately 40% of hemorrhagic stroke survivors develop hydrocephalus. Hyperbaric oxygen (HBO) has been shown to be anti-inflammation following experimental stroke; however, its effect upon post-hemorrhagic hydrocephalus formation is not known. The objective of this study is to investigate whether HBO therapy can effectively reduce hydrocephalus formation and improve neurobehavioral functions in a rat model of subarachnoid hemorrhage (SAH). METHOD: Thirty-eight male Sprague-Dawley rats (300-320 g) rats survived for 21 days from SAH by endovascular perforation or sham surgery were used. At 24 hours after SAH, HBO (3 atmospheres absolute) or normobaric oxygen (NBO) administrated for 1 hour once daily for a total of 7 days. Wire hanging and rotarod testing were conducted at 14 days after SAH, and cognitive functions were evaluated via the Morris water maze, between day 17 to day 21 after surgery. At day 21, rats were sacrificed and cerebroventricular volumes were measured histologically. RESULTS: Hydrocephalus exacerbated neurological deficits after SAH, and HBO multiple treatment tendentially improved the neurobehavioral functions. Spatial learning and memory deficits were noticed after SAH, and rats with hydrocephalus showed worse learning and memory abilities and HBO treatment showed a minor improvement. In the SAH group (room air) 4 rats showed an increased ventricular volume at day 21 after SAH-induction (n = 10). HBO or NBO therapy did not alter the occurrence of hydrocephalus after SAH, as 4 rats in each of these groups showed an increased ventricular volume (n = 10 per group). CONCLUSION: Multiple HBO therapy does not ameliorate hydrocephalus formation in a rat model of SAH; however, HBO tendentially improved the neurological functions and spatial learning and memory abilities in rats with hydrocephalus. PMID- 25132958 TI - Short- and long-term habituation of auditory event-related potentials in the rat. AB - An auditory oddball paradigm in humans generates a long-duration cortical negative potential, often referred to as mismatch negativity. Similar negativity has been documented in monkeys and cats, but it is controversial whether mismatch negativity also exists in awake rodents. To this end, we recorded cortical and hippocampal evoked responses in rats during alert immobility under a typical passive oddball paradigm that yields mismatch negativity in humans. The standard stimulus was a 9 kHz tone and the deviant either 7 or 11 kHz tone in the first condition. We found no evidence of a sustained potential shift when comparing evoked responses to standard and deviant stimuli. Instead, we found repetition induced attenuation of the P60 component of the combined evoked response in the cortex, but not in the hippocampus. The attenuation extended over three days of recording and disappeared after 20 intervening days of rest. Reversal of the standard and deviant tones resulted is a robust enhancement of the N40 component not only in the cortex but also in the hippocampus. Responses to standard and deviant stimuli were affected similarly. Finally, we tested the effect of scopolamine in this paradigm. Scopolamine attenuated cortical N40 and P60 as well as hippocampal P60 components, but had no specific effect on the deviant response. We conclude that in an oddball paradigm the rat demonstrates repetition induced attenuation of mid-latency responses, which resembles attenuation of the N1-component of human auditory evoked potential, but no mismatch negativity. PMID- 25132959 TI - Testicular artery pseudoaneurysm: a case report. AB - This is a case of an unusual cause of a testicular mass and the clinical features associated with its presentation and management. The patient presented with testicular pain and was found to have a testicular mass on ultrasound with a central 1cm anechoic region with arterial wave-form concerning for a pseudoaneurysm. The patient underwent orchiectomy with resolution of his symptoms. This case highlights the presentation of testicular artery pseudoaneurysm and outcome following orchiectomy. PMID- 25132962 TI - Visual record of intertidal disturbance caused by drift ice in the spring on the Atlantic coast of Nova Scotia. AB - In the early spring of 2014, an unusually large amount of sea ice drifted from the Gulf of St. Lawrence, where it had been produced, towards the open Atlantic Ocean through the Cabot Strait, between Nova Scotia and Newfoundland, Canada. In early April, significant amounts of drift ice reached the Atlantic coast of mainland Nova Scotia. The ice floes persisted in those coastal waters for up to 16 days, depending on the location. During that time, the ice fragments caused extensive physical disturbance in rocky intertidal communities, removing high quantities of seaweeds and invertebrates. For example, at a location where the ice stayed for 9 days, the loss of macroalgal and invertebrate biomass was almost total. At a location where the ice stayed for 4 days, losses were lower, albeit still high overall. Such a magnitude of disturbance is not common on this coast, as sea ice had not reached the surveyed locations in the previous 4-5 years. We suggest that the frequency of ice scour events may help to predict intertidal community structure. This notion could be tested through multiannual surveys of ice conditions and biological communities along the Atlantic coast of Nova Scotia. PMID- 25132961 TI - Colonoscopic polyp detection rate is stable throughout the workday including evening colonoscopy sessions. AB - OBJECTIVE: Polyp detection rate (PDR) is an accepted measure of colonoscopy quality. Several factors may influence PDR including time of procedure and order of colonoscopy within a session. Our unit provides evening colonoscopy lists (6-9 pm). We examined whether colonoscopy performance declines in the evening. DESIGN: Data for all National Health Service (NHS) outpatient colonoscopies performed at Norfolk and Norwich University Hospital in 2011 were examined. Timing, demographics, indication and colonoscopy findings were recorded. Statistical analysis was performed using multivariate regression. RESULTS: Data from 2576 colonoscopies were included: 1163 (45.1%) in the morning, 1123 (43.6%) in the afternoon and 290 (11.3%) in the evening. Overall PDR was 40.80%. Males, increasing age and successful caecal intubation were all significantly associated with higher polyp detection. The indications 'faecal occult blood screening' (p<0.001) and 'polyp surveillance' (p<0.001) were strongly positively associated and 'anaemia' (p=0.01) was negatively associated with PDR. Following adjustment for covariates, there was no significant difference in PDR between sessions. With the morning as the reference value, the odds ratio for polyp detection in the afternoon and evening were 0.93 (95% CI = 0.72-1.18) and 1.15 (95%CI = 0.82 1.61) respectively. PDR was not affected by rank of colonoscopy within a list, sedation dose or trainee-involvement. CONCLUSIONS: Time of day did not affect polyp detection rate in clinical practice. Evening colonoscopy had equivalent efficacy and is an effective tool in meeting increasing demands for endoscopy. Standardisation was shown to have a considerable effect as demographics, indication and endoscopist varied substantially between sessions. Evening sessions were popular with a younger population. PMID- 25132960 TI - Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes? AB - Background : Exercise-induced arterial hypertension (EIAH) leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the "cardiac fatigue" caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. METHODS: We used echocardiography and spiroergometry to determine the left ventricular mass (LVM), the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. RESULTS: When comparing triathletes with LVM <220g and athletes with LVM >220g there was a significant difference between blood pressure values (BP) at the anaerobic threshold (185.2+/- 21.5 mmHg vs. 198.8 +/-22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen uptake (relative VO 2max) 57.3 +/-7.5ml/min/kg vs. 59.8+/-9.5ml/min/kg (p=ns). Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. CONCLUSION: Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue. PMID- 25132963 TI - Recent trends in airway management: we are not ready to give up fiberoptic endoscopy. AB - The purpose of this correspondence is to discuss recent findings related to current trends in airway management and to discuss the utilization rates of video laryngoscopes versus traditional techniques in USA, UK, and Canada. To highlight the increased use of video laryngoscopes in difficult airway situations, data on the use of alternative airway devices at our institution collected from 2008 to 2010 are presented alongside the results of previously published surveys collected from 2002 to 2013. PMID- 25132964 TI - Early integration of the individual student in academic activities: a novel classroom concept for graduate education in molecular biophysics and structural biology. AB - BACKGROUND: A key challenge in interdisciplinary research is choosing the best approach from a large number of techniques derived from different disciplines and their interfaces. RESULTS: To address this challenge in the area of Biophysics and Structural Biology, we have designed a graduate level course to teach students insightful use of experimental biophysical approaches in relationship to addressing biological questions related to biomolecular interactions and dynamics. A weekly seminar and data and literature club are used to compliment the training in class. The course contains wet-laboratory experimental demonstration and real-data analysis as well as lectures, grant proposal preparation and assessment, and student presentation components. Active student participation is mandatory in all aspects of the class. Students prepare materials for the class receiving individual and iterative feedback from course directors and local experts generating high quality classroom presentations. CONCLUSIONS: The ultimate goal of the course is to teach students the skills needed to weigh different experimental approaches against each other in addressing a specific biological question by thinking and executing academic tasks like faculty. PMID- 25132965 TI - The occurrence of Enterobacteriaceae producing KPC carbapenemases in a general hospital in Curacao. AB - BACKGROUND: Although the presence of Carbapenemase-producing Enterobacteriaceae (CPE) are extensively documented in North and South America. CPE have not been reported from Curacao. However, recently intercontinental spread was suggested of a KPC carbapenemase producing Klebsiella pneumoniae in a patient in the United Kingdom with previous admission to a hospital in Curacao in 2009. FINDINGS: After the introduction of the CLSI 2010 revised breakpoints, seven patients with carbapenemase-producing Enterobacteriaceae were found in a general hospital in Curacao over a period of 16 months. Four patients carried KPC-2 positive Klebsiella pneumoniae, ST11. Two patients carried KPC-3 positive Klebsiella pneumoniae ST258 and one patient carried a KPC-3 positive Citrobacter freundii. Furthermore, our Klebsiella pneumoniae KPC-2 ST11 strain was matched to the Klebsiella pneumoniae KPC-2 ST11 strain in the United Kingdom. CONCLUSIONS: Introduction of new laboratory methods, and adoption of new guidelines and breakpoints led to the first detection of CPE in Curacao. By matching our Klebsiella pneumoniae KPC-2 ST11 strain to a Klebsiella pneumoniae KPC-2 ST11 strain in the United Kingdom, we suggest that carbapenemase-producing Enterobacteriaceae are probably more prevalent in Curacao than previously recognized. PMID- 25132966 TI - Development of Superoxide Dismutase Mimetic Surfaces to Reduce Accumulation of Reactive Oxygen Species for Neural Interfacing Applications. AB - Despite successful initial recording, neuroinflammatory-mediated oxidative stress products can contribute to microelectrode failure by a variety of mechanisms including: inducing microelectrode corrosion, degrading insulating/passivating materials, promoting blood-brain barrier breakdown, and directly damaging surrounding neurons. We have shown that a variety of anti-oxidant treatments can reduce intracortical microelectrode-mediated oxidative stress, and preserve neuronal viability. Unfortunately, short-term soluble delivery of anti-oxidant therapies may be unable to provide sustained therapeutic benefits due to low bio availability and fast clearance rates. In order to develop a system to provide sustained neuroprotection, we investigated modifying the microelectrode surface with an anti-oxidative coating. For initial proof of concept, we chose the superoxide dismutase (SOD) mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP). Our system utilizes a composite coating of adsorbed and immobilized MnTBAP designed to provide an initial release followed by continued presentation of an immobilized layer of the antioxidant. Surface modification was confirmed by XPS and QCMB-D analysis. Antioxidant activity of composite surfaces was determined using a Riboflavin/NitroBlue Tetrazolium (RF/NBT) assay. Our results indicate that the hybrid modified surfaces provide several days of anti-oxidative activity. Additionally, in vitro studies with BV-2 microglia cells indicated a significant reduction of intracellular and extracellular reactive oxygen species when cultured on composite MnTBAP surfaces. PMID- 25132968 TI - Indications and outcomes in adult lung transplantation. AB - Lung transplantation (LTx) is a treatment option for end-stage lung disease that would be otherwise fatal for specific patient populations. The most common indications for LTx in adults remain to be chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, alpha-1 antitrypsin deficiency, and idiopathic pulmonary arterial hypertension. Recent trends include performing re-transplantation while more patients over the age of 65 years are undergoing LTx. Even with these tendencies, slight improvements in survival have occurred. This article briefly reviews recent developments in adults undergoing LTx. PMID- 25132967 TI - Directed cardiomyogenesis of autologous human induced pluripotent stem cells recruited to infarcted myocardium with bioengineered antibodies. AB - OBJECTIVE: Myocardial infarctions constitute a major factor contributing to non natural mortality world-wide. Clinical trials of myocardial regenerative therapy, currently pursued by cardiac surgeons, involve administration of stem cells into the hearts of patients suffering from myocardial infarctions. Unfortunately, surgical acquisition of these cells from bone marrow or heart is traumatic, retention of these cells to sites of therapeutic interventions is low, and directed differentiation of these cells in situ into cardiomyocytes is difficult. The specific aims of this work were: (1) to generate autologous, human, pluripotent, induced stem cells (ahiPSCs) from the peripheral blood of the patients suffering myocardial infarctions; (2) to bioengineer heterospecific antibodies (htAbs) and use them for recruitment of the ahiPSCs to infarcted myocardium; (3) to initiate in situ directed cardiomyogenesis of the ahiPSCs retained to infarcted myocardium. METHODS: Peripheral blood was drawn from six patients scheduled for heart transplants. Mononuclear cells were isolated and reprogrammed, with plasmids carrying six genes (NANOG, POU5F1, SOX2, KLF4, LIN28A, MYC), to yield the ahiPSCs. Cardiac tissues were excised from the injured hearts of the patients, who received transplants during orthotopic surgery. These tissues were used to prepare in vitro models of stem cell therapy of infarcted myocardium. The htAbs were bioengineered, which simultaneously targeted receptors displayed on pluripotent stem cells (SSEA-4, SSEA-3, TRA-1-60, TRA-1-81) and proteins of myocardial sarcomeres (myosin, alpha-actinin, actin, titin). They were used to bridge the ahiPSCs to the infarcted myocardium. The retained ahiPSCs were directed with bone morphogenetic proteins and nicotinamides to differentiate towards myocardial lineage. RESULTS: The patients' mononuclear cells were efficiently reprogrammed into the ahiPSCs. These ahiPSCs were administered to infarcted myocardium in in vitro models. They were recruited to and retained at the treated myocardium with higher efficacy and specificity, if were preceded with the htAbs, than with isotype antibodies or plain buffers. The retained cells differentiated into cardiomyocytes. CONCLUSIONS: The proof of concept has been attained, for reprogramming the patients' blood mononuclear cells (PBMCs) into the ahiPSCs, recruiting these cells to infarcted myocardium, and initiating their cardiomyogenesis. This novel strategy is ready to support the ongoing clinical trials aimed at regeneration of infarcted myocardium. PMID- 25132969 TI - Pediatric lung transplantation: indications and outcomes. AB - Lung transplantation (LTx) is a treatment option for infants and children with untreatable and otherwise fatal pulmonary diseases. To date, over 1,800 lung transplants have been performed, most frequently in children over the age of five years. The most common indications for transplantation in children overall are cystic fibrosis (CF) and idiopathic pulmonary hypertension (PH). The surfactant protein deficiencies, other interstitial lung diseases (ILDs), and congenital heart disease are important indications among young children and infants. Re transplantation is an option for selected recipients with chronic allograft rejection. Overall survival following pediatric LTx is similar to that encountered in adult patients, with recent registry data indicating a median survival of 4.9 years. Other outcomes such as the incidence of bronchiolitis obliterans (BO) and the presence of key post-transplant co-morbid conditions are also similar to the experience in adult lung transplant recipients. PMID- 25132970 TI - Lung donor selection criteria. AB - The criteria that define acceptable physiologic and social parameters for lung donation have remained constant since their empiric determination in the 1980s. These criteria include a donor age between 25-40, a arterial partial pressure of oxygen (PaO2)/FiO2 ratio greater than 350, no smoking history, a clear chest X ray, clean bronchoscopy, and a minimal ischemic time. Due to the paucity of organ donors, and the increasing number of patients requiring lung transplant, finding a donor that meets all of these criteria is quite rare. As such, many transplants have been performed where the donor does not meet these stringent criteria. Over the last decade, numerous reports have been published examining the effects of individual acceptance criteria on lung transplant survival and graft function. These studies suggest that there is little impact of the historical criteria on either short or long term outcomes. For age, donors should be within 18 to 64 years old. Gender may relay benefit to all female recipients especially in male to female transplants, although results are mixed in these studies. Race matched donor/recipients have improved outcomes and African American donors convey worse prognosis. Smoking donors may decrease recipient survival post transplant, but provide a life saving opportunity for recipients that may otherwise remain on the transplant waiting list. No specific gram stain or bronchoscopic findings are reflected in recipient outcomes. Chest radiographs are a poor indicator of lung donor function and should not adversely affect organ usage aside for concerns over malignancy. Ischemic time greater than six hours has no documented adverse effects on recipient mortality and should not limit donor retrieval distances. Brain dead donors and deceased donors have equivalent prognosis. Initial PaO2/FiO2 ratios less than 300 should not dissuade donor organ usage, although recruitment techniques should be implemented with intent to transplant. PMID- 25132972 TI - Ex vivo lung perfusion. AB - Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID- 25132973 TI - The surgical technique of bilateral sequential lung transplantation. AB - Since the first successful lung transplant performed three decades ago, the technique of lung transplantation has evolved with acceptable short- and long term outcomes such that it has become the standard for those with end stage pulmonary disease. Herein, we describe our current favored approach and discuss some of the current areas in need of further investigation as they relate to the technical aspects of the operation. PMID- 25132971 TI - Immunosuppression in lung transplantation. AB - Lung transplantation can be a life-saving procedure for those with end-stage lung diseases. Unfortunately, long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over 6 years. Immunosuppressive regimens are employed to reduce the rate of rejection, and while protocols vary from center to center, conventional maintenance therapy consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate, sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung transplant centers also utilize induction therapy, with polyclonal antibody preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2 receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This review summarizes these agents and the data surrounding their use in lung transplantation, as well as additional common and novel therapies in lung transplantation. Despite the progression of the management of lung transplant recipients, they continue to be at high risk of treatment-related complications, and poor graft and patient survival. Randomized clinical trials are needed to allow for the development of better agents, regimens and techniques to address above mentioned issues and reduce morbidity and mortality among lung transplant recipients. PMID- 25132974 TI - Bridge to lung transplantation and rescue post-transplant: the expanding role of extracorporeal membrane oxygenation. AB - Over the last several decades, the growth of lung transplantation has been hindered by a much higher demand for donor lungs than can be supplied, leading to considerable waiting time and mortality among patients waiting for transplant. This has led to the search for an alternative bridging strategy in patients with end-stage lung disease. The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation as well as a rescue strategy post-transplant for primary graft dysfunction (PGD) has been studied previously, however due to initially poor outcomes, its use was not heavily instituted. In recent years, with significant improvement in technologies, several single and multi-center studies have shown promising outcomes related to the use of ECMO as a bridging strategy as well as a therapy for patients suffering from PGD post-transplant. These results have challenged our current notion on ECMO use and hence forced us to reexamine the utility, efficacy and safety of ECMO in conjunction with lung transplantation. Through this review, we will address the various aspects related to ECMO use as a bridge to lung transplantation as well as a rescue post transplant in the treatment of PGD. We will emphasize newer technologies related to ECMO use, examine recent observational studies and randomized trials of ECMO use before and after lung transplantation, and reflect upon our own institutional experience with the use of ECMO in these difficult clinical situations. PMID- 25132977 TI - Heart transplantation. AB - Heart failure remains a major global problem with approximately 6 million individuals suffering from heart failure in the United States alone. The surgical technique of heart transplantation, popularized by Dr. Norman Shumway, has led to its success and currently remains the best treatment options for patients with end-stage. However, with the continued limitation of donor organs and the rapid development of ventricular assist device technology, the number of patients bridged to transplant with mechanical circulatory support has increased significantly. This has created some new technical challenges for heart transplantation. Therefore, it is now important to be familiar with multiple new technical challenges associated with the surgical techniques of heart transplantation with an ultimate goal in reducing donor heart ischemic time, recipient cardiopulmonary bypass time and post-operative complications. In this review, we described our technique of heart transplantation including the timing of the operation, recipient cardiectomy and donor heart implantation. PMID- 25132976 TI - Donor selection in heart transplantation. AB - There is increased scrutiny on the quality in health care with particular emphasis on institutional heart transplant survival outcomes. An important aspect of successful transplantation is appropriate donor selection. We review the current guidelines as well as areas of controversy in the selection of appropriate hearts as donor organs to ensure optimal outcomes. This decision is paramount to the success of a transplant program as well as recipient survival and graft function post-transplant. PMID- 25132975 TI - Pediatric heart transplantation-indications and outcomes in the current era. AB - Pediatric heart transplantation (HTx) remains an important treatment option in the care of children with end-stage heart disease, whether it is secondary to cardiomyopathy or congenital heart disease (CHD). As surgical outcomes for CHD have improved, the indications for pediatric HTx have had to be dynamic, not only for children with CHD but also for the growing population of adults with CHD. As the field of pediatric HTx has evolved, the outcomes for children undergoing HTx have improved. This is undoubtedly due to the continued research efforts of both single-center studies, as well as research collaboratives such as the International Society for Heart and Lung Transplantation (ISHLT) and the Pediatric Heart Transplant Study (PHTS) group. Research collaboratives are increasingly important in pediatric HTx as single center studies for a limited patient population may not elicit strong enough evidence for practice evolution. Similarly, complications that limit the long term graft survival may occur in a minority of patients thus pooled experience is essential. This review focuses on the indications and outcomes for pediatric HTx, with a special emphasis on studies generated by these research collaboratives. PMID- 25132978 TI - Left ventricular assist devices as a bridge to cardiac transplantation. AB - Heart failure remains a significant cause of morbidity and mortality, affecting over five million patients in the United States. Continuous-flow left ventricular assist devices (LVAD) have become the standard of care for patients with end stage heart failure. This review highlights the current state of LVAD as a bridge to transplant (BTT) in patients requiring mechanical circulatory support (MCS). PMID- 25132979 TI - Adult heart transplant: indications and outcomes. AB - Cardiac transplantation is the treatment of choice for many patients with end stage heart failure (HF) who remain symptomatic despite optimal medical therapy. For carefully selected patients, heart transplantation offers markedly improved survival and quality of life. Risk stratification of the large group of patients with end-stage HF is essential for identifying patients who are most likely to benefit, particularly as the number of suitable donors is insufficient to meet demand. The indications for heart transplant and review components of the pre transplant evaluation, including the role for exercise testing and risk scores such as the Heart Failure Survival Score (HFSS) and Seattle Heart Failure Model (SHFM) are summarized. Common contraindications are also discussed. Outcomes, including survival and common complications such as coronary allograft vasculopathy are reviewed. PMID- 25132980 TI - Heart-lung transplantation: pediatric indications and outcomes. AB - As indications for heart-lung transplant (HLT) have changed to some degree in the past 30 years, this treatment is being used less frequently in children due to more advanced care of severe heart and lung disease. This is fortunate as the outcomes for HLT are poor compared to other solid organ transplants and this is mainly due to the poorer outcome of the lung graft. PMID- 25132981 TI - Heart-lung transplantation: adult indications and outcomes. AB - Combined heart-lung transplantation remains the only definitive therapy for patients who have both end-stage heart failure and end-stage lung failure. The most common indication is congenital heart disease (CHD) and the proportion is increasing for acquired heart disease concomitant with pulmonary hypertension and/or intrinsic lung diseases. Previously, idiopathic pulmonary hypertension was the most common indication. However, it has been shown that right ventricular failure can be reversed after double lung transplantation. Therefore, patients with idiopathic pulmonary arterial hypertension (IPAH) should not undergo combined heart-lung transplantation unless left ventricular dysfunction co exists. The ISHLT registry data shows survival after heart-lung transplantation is improving, but still its survival rates are 71% at 3 months, 63% at 1 year, 44% at 5 years and 31% at 10 years. With appropriate patient selection and surgical expertise, these outcomes should improve further. PMID- 25132983 TI - Heart-lung transplantation. AB - Heart-lung transplantation itself is not a particularly difficult operation technically. It is the setting in which this procedure is performed which is difficult. The three issues of importance in a successful outcome are appropriate harvest of the heart-lung bloc from the donor, careful explant of the heart and lungs of the recipient, and finally the implant of the heart-lung bloc into the recipient. None of this requires extraordinary technical skill, but does require careful coordination and planning as well as adhering to some fundamental principles. One of the major pitfalls encountered is bleeding related to the explant procedure. Another is graft failure related to harvest and/or the implant procedure. The third is injury to either the phrenic nerve(s) or the left recurrent laryngeal nerve related to the explant procedure. Heart-lung transplantation is a major investment in resources of all sorts including financial, personnel, as well as the organs themselves. It is absolutely imperative that this procedure be performed only by experienced surgeons in centers with established expertise. PMID- 25132982 TI - Preservation solutions for cardiac and pulmonary donor grafts: a review of the current literature. AB - Hypothermic preservation of donor grafts is imperative to ameliorate ischemia related cellular damage prior to organ transplantation. Numerous solutions are in existence with widespread variability among transplant centers as to a consensus regarding the optimal preservation solution. Here, we present a concise review of pertinent preservation studies involving cardiac and pulmonary allografts in an attempt to minimize the variability among institutions and potentially improve graft and patient survival. A biochemical comparison of common preservation solutions was undertaken with an emphasis on Euro Collins (EC), University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK), Celsior (CEL), Perfadex (PER), Papworth, and Plegisol. An appraisal of the literature ensued containing the aforementioned preservation solutions in the setting of cardiac and pulmonary transplantation. Available evidence supports UW solution as the preservation solution of choice for cardiac transplants with encouraging outcomes relative to notable contenders such as CEL. Despite its success in the setting of cardiac transplantation, its use in pulmonary transplantation remains suboptimal and improved outcomes may be seen with PER. Together, we suggest, based on the literature that the use of UW solution and PER for cardiac and pulmonary transplants, respectively may improve transplant outcomes such as graft and patient survival. PMID- 25132984 TI - Overview of paediatric heart-lung transplantation: a global perspective. PMID- 25132985 TI - The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy. AB - The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD). The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor) and Nrf2 (nuclear factor erythroid 2-related factor 2), which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1. PMID- 25132987 TI - Subclinical Iodine Deficiency among Pregnant Women in Haramaya District, Eastern Ethiopia: A Community-Based Study. AB - Background. Iodine deficiency in pregnancy is a worldwide problem. This study aimed to assess prevalence and predictors of subclinical iodine deficiency among pregnant women in Haramaya district, eastern Ethiopia. Methods. A cross sectional, community-based study was conducted on 435 pregnant women existing in ten randomly selected rural kebeles (kebele is the smallest administrative unit in Ethiopia). Data on the study subjects' background characteristics, dietary habits, and gynecological/obstetric histories were collected via a structured questionnaire. UIC of <150 MUg/L defined subclinical iodine deficiency. Data were analyzed by Stata 11. A multivariable logistic regression was used to identify the predictors of subclinical iodine deficiency. Results. The median urinary iodine concentration (MUIC) was 58.1 MUg/L and 82.8% of the women who had subclinical iodine deficiency. The risk of subclinical iodine deficiency was reduced by the use of iodized salt (AOR = 0.13) and by intake of milk twice a month or more (AOR = 0.50), but it was increased by maternal illiteracy (AOR = 3.52). Conclusion. Iodine nutritional status of the pregnant women was poor. This shows that women and their children are exposed to iodine deficiency and its adverse effects. Thus, they need urgent supplementation with iodine and improved access to and intake of iodized salt and milk during pregnancy. PMID- 25132988 TI - Lovastatin as an adjuvant to lithium for treating manic phase of bipolar disorder: a 4-week, randomized, double-blind, placebo-controlled clinical trial. AB - Objectives. Many patients with bipolar disorder suffer from metabolic disorder. Lovastatin is effective for treating major depression. This double-blind randomized placebo controlled clinical trial investigates whether lovastatin is a useful adjuvant to lithium for treating mania. Methods. Fifty-four patients with bipolar disorder-manic phase were randomly allocated into lovastatin or placebo group. The clinical symptoms were assessed at baseline, week 2, and week 4 using Young Mania Rating Scale. Adverse effects were checked. Results. Forty-six out of 54 patients completed this trial. The mania score in the lovastatin group decreased from 40.6 (11.1) at baseline to 12.9 (8.7) and 4.1 (5.4) at weeks 2 and 4, respectively. The score in the placebo group decreased from 41.0 (11.2) at baseline to 12.8 (8.07) and 5.8 (4.6) at weeks 2 and 4, respectively. However, there was no significant difference between groups at week 2 and week 4. The adverse effects rates were comparable between the two groups. No serious adverse effect was found. Tremor and nausea were the most common adverse effects. Conclusions. Lovastatin neither exacerbated nor decreased the symptoms of mania in patients with bipolar disorder. Current results support that the combination of lovastatin with lithium is tolerated well in bipolar disorder. The trial was registered with the Iranian Clinical Trials Registry (IRCT201302203930N18). PMID- 25132986 TI - Cardiometabolic risk assessments by body mass index z-score or waist-to-height ratio in a multiethnic sample of sixth-graders. AB - Convention defines pediatric adiposity by the body mass index z-score (BMIz) referenced to normative growth charts. Waist-to-height ratio (WHtR) does not depend on sex-and-age references. In the HEALTHY Study enrollment sample, we compared BMIz with WHtR for ability to identify adverse cardiometabolic risk. Among 5,482 sixth-grade students from 42 middle schools, we estimated explanatory variations (R (2)) and standardized beta coefficients of BMIz or WHtR for cardiometabolic risk factors: insulin resistance (HOMA-IR), lipids, blood pressures, and glucose. For each risk outcome variable, we prepared adjusted regression models for four subpopulations stratified by sex and high versus lower fatness. For HOMA-IR, R (2) attributed to BMIz or WHtR was 19%-28% among high fatness and 8%-13% among lower-fatness students. R (2) for lipid variables was 4% 9% among high-fatness and 2%-7% among lower-fatness students. In the lower fatness subpopulations, the standardized coefficients for total cholesterol/HDL cholesterol and triglycerides tended to be weaker for BMIz (0.13-0.20) than for WHtR (0.17-0.28). Among high-fatness students, BMIz and WHtR correlated with blood pressures for Hispanics and whites, but not black boys (systolic) or girls (systolic and diastolic). In 11-12 year olds, assessments by WHtR can provide cardiometabolic risk estimates similar to conventional BMIz without requiring reference to a normative growth chart. PMID- 25132989 TI - Validation of a new instrument for self-assessment of nurses' core competencies in palliative care. AB - Competence can be seen as a prerequisite for high quality nursing in clinical settings. Few research studies have focused on nurses' core competencies in clinical palliative care and few measurement tools have been developed to explore these core competencies. The purpose of this study was to test and validate the nurses' core competence in palliative care (NCPC) instrument. A total of 122 clinical nurse specialists who had completed a postbachelor program in palliative care at two university colleges in Norway answered the questionnaire. The initial analysis, with structural equation modelling, was run in Mplus 7. A modified confirmatory factor analysis revealed the following five domains: knowledge in symptom management, systematic use of the Edmonton symptom assessment system, teamwork skills, interpersonal skills, and life closure skills. The actual instrument needs to be tested in a practice setting with a larger sample to confirm its usefulness. The instrument has the potential to be used to refine clinical competence in palliative care and be used for the training and evaluation of palliative care nurses. PMID- 25132990 TI - Implementation intentions as a strategy to increase the notification rate of potential ocular tissue donors by nurses: a clustered randomized trial in hospital settings. AB - Aim. The purpose of this study is to evaluate the impact, among nurses in hospital settings, of a questionnaire-based implementation intentions intervention on notification of potential ocular tissue donors to donation stakeholders. Methods. This randomized intervention was clustered at the level of hospital departments with two study arms: questionnaire-based implementation intentions intervention and control. In the intervention group, nurses were asked to plan specific actions if faced with a number of barriers when reporting potential ocular donors. The primary outcome was the potential ocular tissue donors' notification rate before and after the intervention. Analysis was based on a generalized linear model with an identity link and a binomial distribution. Results. We compared outcomes in 26 departments from 5 hospitals, 13 departments per condition. The implementation intentions intervention did not significantly increase the notification rate of ocular tissue donors (intervention: 23.1% versus control: 21.1%; chi (2) = 1.14, 2; P = 0.56). Conclusion. A single and brief implementation intentions intervention among nurses did not modify the notification rate of potential ocular tissue donors to donation stakeholders. Low exposure to the intervention was a major challenge in this study. Further studies should carefully consider a multicomponent intervention to increase exposure to this type of intervention. PMID- 25132992 TI - Endovascular embolisation of visceral artery pseudoaneurysms. AB - Objective. To evaluate the technical success, safety, and outcome of endovascular embolization procedure in management of visceral artery pseudoaneurysms. Materials and Methods. 46 patients were treated for 53 visceral pseudoaneurysms at our institution. Preliminary diagnostic workup in all cases was performed by contrast enhanced abdominal CT scan and/or duplex ultrasound. In all patients, embolization was performed as per the standard departmental protocol. For data collection, medical records and radiology reports of all patients were retrospectively reviewed. Technical success, safety, and outcome of the procedure were analyzed. Results. Out of 46 patients, 13 were females and 33 were males. Mean patient age was 44.79 +/- 13.9 years and mean pseudoaneurysm size was 35 +/- 19.5 mm. Technical success rate for endovascular visceral pseudoaneurysm coiling was 93.47% (n = 43). Complication rate was 6.52% (n = 3). Followup was done for a mean duration of 21 +/- 1.6 months (0.5-69 months). Complete resolution of symptoms or improvement in clinical condition was seen in 36 patients (80%) out of those 45 in whom procedure was technically successful. Conclusion. Results of embolization of visceral artery pseudoaneurysms with coils at our center showed high success rate and good short term outcome. PMID- 25132993 TI - Psychological Impacts among Older and Younger People Living with HIV/AIDS in Nanning, China. AB - Objectives. The HIV epidemic has drastically increased among older adults in China, yet little research has examined the psychological impacts among older and younger people living with HIV/AIDS (PLWHAs). This study examined and compared self-efficacy, depression, well-being, and quality of life among older and younger PLWHAs in China. Method. A two-stage sampling procedure was used to recruit a final sample of 148 participants. Older adults were defined as age 50 and older. Result. Compared to younger PLWHAs aged 18-49 years old, older PLWHAs reported lower levels of well-being (7.6 versus 11.4), higher levels of depression (18.6 versus 15.8), and poorer quality of life. Self-efficacy was similar among older (23.9) and younger (24.6) PLWHAs. A higher level of depression among older PLWHAs was associated with much lower levels of subjective well-being and quality of life (physical health and psychological health). Conclusion. The findings suggest that older PLWHAs face psychological problems and mental health challenges beyond those experienced by younger PLWHAs. Intervention programs dedicated to improving mental health and quality of life are greatly needed for HIV infected older adults. PMID- 25132991 TI - The epidemiology of pulmonary nontuberculous mycobacteria: data from a general hospital in Athens, Greece, 2007-2013. AB - BACKGROUND: The epidemiology of pulmonary nontuberculous mycobacteria (NTM) in Greece is largely unknown. OBJECTIVES: To determine the incidence and the demographic, microbiological, and clinical characteristics of patients with pulmonary NTM infection and pulmonary NTM disease. METHODS: A retrospective review of the demographic, microbiological, and clinical characteristics of patients with NTM culture-positive respiratory specimens from January 2007 to May 2013. RESULTS: A total of 120 patients were identified with at least one respiratory NTM isolate and 56 patients (46%) fulfilled the microbiological ATS/IDSA criteria for NTM disease. Of patients with adequate data, 16% fulfilled the complete ATS/IDSA criteria for NTM disease. The incidence of pulmonary NTM infection and disease was 18.9 and 8.8 per 100.000 inpatients and outpatients, respectively. The spectrum of NTM species was high (13 species) and predominated by M. avium-intracellulare complex (M. avium (13%), M. intracellulare (10%)), M. gordonae (14%), and M. fortuitum (12%). The ratio of isolation of NTM to M. tuberculosis in all hospitalized patients was 0.59. CONCLUSIONS: The first data on the epidemiology of pulmonary NTM in Athens, Greece, are presented. NTM infection is common in patients with chronic respiratory disease. However, only a significantly smaller proportion of patients fulfill the criteria for NTM disease. PMID- 25132994 TI - Sound Lateralization Test Distinguishes Unimpaired MS Patients from Healthy Controls. AB - There is an urgent need to develop a practical and reliable clinical measure of disease progression in early and mild MS. We hypothesized that a test of sound lateralization, which is exquisitely sensitive to transmission delays in auditory brainstem, could be more useful for detecting processing speed deficits in mildly impaired MS subjects than standard cognitive tasks. Objective. To develop a practical test of sound lateralization for the clinic and to compare performance of MS subjects with variable disability and healthy subjects on Sound Lateralization Test (SLT) and two speed-of-processing tasks. Design. 42 healthy controls and 90 subjects with clinically definite MS, divided into no, mild, and moderate disability strata, were administered the Symbol Digit Modalities Test (SDMT), and 3-second Paced Auditory Serial Addition Test (PASAT). Results. All of the tests showed an overall difference in performance between controls and the three MS groups, but only the SLT measured a significant difference between controls and the no disability group. Conclusion. SLT is rapidly applied, technically simple, and superior to standard processing speed tests for discriminating between healthy controls and nondisabled MS subjects. SLT should be investigated as an outcome measure in early-phase trials and for monitoring early disease progression in the clinic. PMID- 25132995 TI - Similarity of fibroglandular breast tissue content measured from magnetic resonance and mammographic images and by a mathematical algorithm. AB - Women with high breast density (BD) have a 4- to 6-fold greater risk for breast cancer than women with low BD. We found that BD can be easily computed from a mathematical algorithm using routine mammographic imaging data or by a curve fitting algorithm using fat and nonfat suppression magnetic resonance imaging (MRI) data. These BD measures in a strictly defined group of premenopausal women providing both mammographic and breast MRI images were predicted as well by the same set of strong predictor variables as were measures from a published laborious histogram segmentation method and a full field digital mammographic unit in multivariate regression models. We also found that the number of completed pregnancies, C-reactive protein, aspartate aminotransferase, and progesterone were more strongly associated with amounts of glandular tissue than adipose tissue, while fat body mass, alanine aminotransferase, and insulin like growth factor-II appear to be more associated with the amount of breast adipose tissue. Our results show that methods of breast imaging and modalities for estimating the amount of glandular tissue have no effects on the strength of these predictors of BD. Thus, the more convenient mathematical algorithm and the safer MRI protocols may facilitate prospective measurements of BD. PMID- 25132996 TI - Diagnosis of spontaneous bacterial peritonitis and an in situ hybridization approach to detect an "unidentified" pathogen. AB - Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication in cirrhotic patients with ascites. Although identifying the pathogen(s) plays a major role in the management of infectious diseases, ascitic fluid cultures often show negative results in patients with clinical signs and symptoms of SBP, and ascitic fluid cell analyses are the gold standard method for diagnosing SBP. SBP is generally diagnosed based on an increased number of polymorphonuclear neutrophils in the ascitic fluid (>250/mm(3)), and the identification of the causal pathogen may not be given consideration. We newly developed an in situ hybridization (ISH) method to provide early and direct evidence of bacterial infection in ascites in patients with SBP. This paper will review the diagnosis of SBP, including our novel approach with ISH method to detect bacterial DNA in SBP ascitic fluid. PMID- 25132999 TI - Ectopic 3rd molar tooth in the maxillary antrum. AB - Location of ectopic tooth in a nondentate area like the maxillary antrum is rare. A 17-year-old boy, with one year history of recurrent right facial swelling and radiographic finding of a maxillary third molar tooth located at the posterior wall of the maxillary antrum, is presented. Under endotracheal intubation, the tooth was extracted through a Caldwell-Luc antrostomy approach and patient had an uneventful recovery and has been symptom free for eight months. Ectopic tooth in the maxillary antrum is rare and is commonest with maxillary third molar. It may be symptomless but is more commonly associated with inflammatory symptoms. The treatment of choice is surgical excision which is mostly carried out with Caldwell-Luc approach, even though endoscopic approach is being reported. PMID- 25132998 TI - Cholangiocarcinoma with respect to IgG4 Reaction. AB - IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in cancer patients and in patients with IgG4-related diseases. Extrahepatic cholangiocarcinomas including gall bladder cancer are often accompanied by significant IgG4 reactions; these reactions show a negative correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of immune surveillance is associated with cytotoxic T cells. The regulatory cytokine IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell switching to IgG4 in the presence of IL-4. Cholangiocarcinoma cells may function as nonprofessional antigen presenting cells that indirectly induce IgG4 reactions via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10 producing cells that directly induce IgG4 reactions. Moreover, IgG4-related disease is a high-risk factor for cancer development; IgG4-related sclerosing cholangitis (IgG4-SC) cases associated with cholangiocarcinoma or its precursor lesion biliary intraepithelial neoplasia (BilIN) have been reported. IgG4 positive cell infiltration is an important finding of IgG4-SC but is not a histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its differentiation from cholangiocarcinoma remains important. PMID- 25133000 TI - Nonsurgical treatment of two periapical lesions with calcium hydroxide using two different vehicles. AB - Calcium hydroxide is used extensively as an intracanal medicament in endodontics for many years. It is used in various clinical situations such as to promote apexification, to repair perforation, to enhance healing of periapical lesions, to control root resorption, and to control exudation in teeth with persistent periapical inflammation. This paper presents a case report in which Ca(OH)2 was used as an intracanal medicament for treatment of periradicular lesions using two different vehicles in two different teeth of same patient. PMID- 25132997 TI - Genetic diseases that predispose to early liver cirrhosis. AB - Inherited liver diseases are a group of metabolic and genetic defects that typically cause early chronic liver involvement. Most are due to a defect of an enzyme/transport protein that alters a metabolic pathway and exerts a pathogenic role mainly in the liver. The prevalence is variable, but most are rare pathologies. We review the pathophysiology of such diseases and the diagnostic contribution of laboratory tests, focusing on the role of molecular genetics. In fact, thanks to recent advances in genetics, molecular analysis permits early and specific diagnosis for most disorders and helps to reduce the invasive approach of liver biopsy. PMID- 25133001 TI - Cardiac failure as an unusual presentation in a patient with history of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is the most well-known form of motor neuron diseases in which both upper and lower motor neurons are involved in this disease. We presented an unusual case of ALS whom had presented with chief complaint of dyspnea. Cardiac failure was diagnosed at the final stage of the ALS disease. The pathogenetic mechanism leading to an elevated occurrence of cardiomyopathy in ALS is not comprehensible. Dilated cardiomyopathy has been explained in some previous studies. Based on the collected data, it was hypothesized that cardiomyopathy is underdiagnosed in the ALS population, probably because symptoms are masqueraded as a result of the patients' disability. It was suggested that in all motor neuron diseases a serial cardiological evaluation should be executed, including annual echocardiography. PMID- 25133002 TI - Carcinoma buccal mucosa underlying a giant cutaneous horn: a case report and review of the literature. AB - Cutaneous horn is a conical, dense, and hyperkeratotic protrusion that often appears similar to the horn of an animal. Giant cutaneous horns are rare; no incidence or prevalence has been reported. The significance of cutaneous horns is that they occur in association with, or as a response to, a wide variety of underlying benign, premalignant, and malignant cutaneous diseases. A case of giant cutaneous horn of left oral commissure along with carcinoma left buccal mucosa is reported here as an extremely rare oral/perioral pathology. PMID- 25133004 TI - Primary renal angiosarcoma with extensive necrosis: a difficult diagnosis. AB - Angiosarcoma of the kidney is an exceedingly rare and aggressive neoplasm. Very few cases have been reported in the English literature to date. We report a case of primary renal angiosarcoma with extensive necrosis and discuss its diagnostic difficulties. An 86-year-old male presented with a 12 cm necrotic renal mass and multiple pulmonary and hepatic nodules. A CT guided renal biopsy revealed extensive necrosis and few vascular channels lined by malignant endothelial cells. Diagnosis was given on a morphologic base and proven by an immunohistochemical study. Primary renal angiosarcoma should be included among the differential diagnosis of necrotic renal lesions. PMID- 25133003 TI - Thyroid-like follicular carcinoma of the kidney in a young patient with history of pediatric acute lymphoblastic leukemia. AB - Thyroid-like follicular carcinoma of the kidney (TLFCK) is a rare histological variant of renal cell carcinoma not currently included in the World Health Organization classification of renal tumors. Only 24 previous cases of TLFCK have been reported to date. We report a case of TLFCK in a 19-year-old woman with history of pediatric acute lymphoblastic leukemia. This patient is the youngest with TLFCK to be reported to date and the first with history of lymphoblastic leukemia. The development of TLFCK in a young patient with history of lymphoblastic leukemia is interesting and suggests that genes involved in leukemogenesis may also be important for TLFCK pathogenesis. Recognition of TLFCK is important to distinguish it from other conditions that show thyroid-like features, as a misdiagnosis can result in adverse patient care. PMID- 25133005 TI - Primary hairy cell leukemia/lymphoma of the breast: a case report and review of the literature. AB - Hairy cell leukemia/lymphoma (HCL) is a rare B-cell neoplasm primarily involving spleen, bone marrow, and blood. However, other sites of primary involvement do occur and can present a diagnostic and therapeutic challenge. We present an unusual case of HCL involving predominantly the breast that was diagnosed as an incidental finding during an elective reduction mammoplasty in an otherwise healthy asymptomatic woman. Bone marrow performed for staging revealed limited involvement by HCL. Notably, there was no splenomegaly and/or involvement of other extramedullary sites. The peripheral blood revealed minimal involvement detected by flow cytometry. Extensive immunohistochemical studies supported by positive BRAF V600E mutational status confirmed the diagnosis of HCL. The patient remains asymptomatic without treatment one year following the diagnosis. This is the first case of a well-documented HCL presenting primarily in the breast in an asymptomatic patient. We review the literature on extramedullary, extrasplenic involvement by HCL and discuss the diagnostic challenges as well as the utility of immunohistochemistry and molecular studies in the diagnosis of atypical presentations of HCL. PMID- 25133006 TI - MRI in diagnosis of a giant prostatic utricle. AB - A prostatic utricle cyst is an epithelial lined diverticulum arising from the prostatic urethra and usually asymptomatic when small. When enlarged, it may be symptomatic and is typically accompanied by hypospadias. We present a case of a markedly enlarged prostatic utricle in a neonate without hypospadias, demonstrated on voiding cystourethrography (VCUG), ultrasound, and 1.5 Tesla MRI. PMID- 25133007 TI - Digital vasculitis in a patient with rheumatoid arthritis responded well to adalimumab. AB - 42-year-old old female patient, followed up with diagnosis of rheumatoid arthritis for 15 years, was admitted with necrotising ulcer of left hand 1st and 2nd fingertips and pain, swelling, limitation of movement, and morning stiffness at bilateral wrist, and metacarpophalangeal and proximal interphalangeal joints. Laboratory tests revealed elevated acute phase reactants. Radial and ulnar arteries were clear in upper extremity Doppler ultrasound. The patient was diagnosed as RA activation and digital ulcer and administered iloprost infusion for five days and 1 mg/kg corticosteroid and 20 mg/week methotrexate (MTX). After one month, a partial regression of clinical and laboratory findings was observed. However, 6 months later, due to relapsed and increased complaints and findings, adalimumab 40 mg was administered. Two months later, clinical and laboratory findings apparently decreased. PMID- 25133009 TI - Concomitant urothelial cancer and renal tuberculosis. AB - We report a case of coexisting urothelial cancer and renal tuberculosis in the same kidney. The patient is a 72-year-old female with a remote history of treated pulmonary tuberculosis who presented with haematuria, initial investigation of which elucidated no definitive cause. Almost 1 year later, a diagnosis of metastatic urinary tract cancer was made. The patient received chemotherapy for advanced collecting duct type renal cell carcinoma, based on histological features of renal biopsy. Subsequent confirmatory immunostains however led to a revised diagnosis of urothelial cancer, necessitating a change in chemotherapy regimen. A diagnosis of ipsilateral renal tuberculosis was made based on TB-PCR testing of renal biopsy tissue and anti-TB therapy was coadministered with chemotherapy. The patient died 9 months after diagnosis of metastatic urothelial cancer. PMID- 25133008 TI - Achalasia Secondary to Submucosal Invasion by Poorly Differentiated Adenocarcinoma of the Cardia, Siewert II: Consideration on Preoperative Workup. AB - Secondary achalasia due to submucosal invasion of cardia by gastric cancer is a rare condition. We report a case of pseudoachalasia, secondary to the involvement of gastroesophageal junction by poorly differentiated gastric cancer, initially mistaken as idiopathic form. We focus on the difficulty to establish differential diagnosis only on the basis of routine exams and we stress the necessity of "second level" instrumental exams; EUS in routine workup in selected patients should be considered. We support that routine workup based on history, clinical presentation, radiological and endoscopic findings, and certainly manometry could be insufficient for a correct differential diagnosis between primary and secondary forms in some patients. PMID- 25133010 TI - Bridging endovascular therapy and subsequent surgical repair for the treatment of infected aneurysms after percutaneous cardiac intervention. AB - Bridging endovascular therapy, accompanied by a second stage open surgical repair was used to treat a rare case of infected aneurysms alongside external iliac artery after a percutaneous cardiac intervention. Because these aneurysms require early treatment, we suggest this approach, in order to avoid immediate, major surgery in a recently symptomatic cardiac and bacteremic patient receiving dual antiplatelet therapy. The approach seems to be safe and durable. PMID- 25133011 TI - Poststroke muscle architectural parameters of the tibialis anterior and the potential implications for rehabilitation of foot drop. AB - Poststroke dorsiflexor weakness and paretic limb foot drop increase the risk of stumbling and falling and decrease overall functional mobility. It is of interest whether dorsiflexor muscle weakness is primarily neurological in origin or whether morphological differences also contribute to the impairment. Ten poststroke hemiparetic individuals were imaged bilaterally using noninvasive medical imaging techniques. Magnetic resonance imaging was used to identify changes in tibialis anterior muscle volume and muscle belly length. Ultrasonography was used to measure fascicle length and pennation angle in a neutral position. We found no clinically meaningful bilateral differences in any architectural parameter across all subjects, which indicates that these subjects have the muscular capacity to dorsiflex their foot. Therefore, poststroke dorsiflexor weakness is primarily neural in origin and likely due to muscle activation failure or increased spasticity of the plantar flexors. The current finding suggests that electrical stimulation methods or additional neuromuscular retraining may be more beneficial than targeting muscle strength (i.e., increasing muscle mass). PMID- 25133013 TI - Prevalence of bla NDM, bla PER, bla VEB, bla IMP, and bla VIM Genes among Acinetobacter baumannii Isolated from Two Hospitals of Tehran, Iran. AB - Background and Objectives. The aim of this study was to determine the frequency of bla NDM, bla PER, bla VEB, bla IMP, and bla VIM type genes among A. baumannii isolates from hospitalized patients in two hospitals in Tehran, Iran. Patients and Methods. Antibiotic susceptibility tests were performed by Kirby-Bauer disc diffusion and Broth microdilution methods. The frequency of MBL (metallo-beta lactamase) and ESBL (extended-spectrum-beta-lactamase) producers was evaluated by CDDT. The beta -lactamases genes were detected by PCR and sequencing methods. Results. The resistance of A. baumannii isolates against tested antibiotics was as follows: 103 (95.4%) to ceftazidime, 108 (100%) to cefotaxime, 105 (95.7%) to cefepime, 99 (91.7%) to imipenem, 99 (91.7%) to meropenem, 87 (80.6%) to amikacin, 105 (97.2%) to piperacillin, 100 (92.6%) to ciprofloxacin, 103 (95.4%) to piperacillin/tazobactam, 44 (40.7%) to gentamicin, 106 (98.1%) to ampicillin/sulbactam, 106 (98.1%) to co-trimoxazole, 87 (80.6%) to tetracycline, and 1 (1.8%) to colistin. Using combined disk diffusion test, 91 (84.2%) and 86 (86.86%) were ESBL and MBL producers, respectively. The prevalence of bla PER-1, bla VEB-1, bla IMP-1, and bla VIM-1 genes was 71 (78.03%), 36 (39.5%), 3 (3.48%), and 15 (17.44%), respectively. Conclusions. The prevalence of ESBLs and MBLs producing A. baumannii strains detected in this study is a major concern and highlights the need of infection control measures. PMID- 25133012 TI - Claw lesions causing clinical lameness in lactating holstein frisian crossbred cows. AB - The objective of this study was to identify claw lesions causing clinical lameness in lactating Holstein Frisian (HF) crossbred cows in dairy cattle. Seventy dairy farmers were interviewed at the monthly meetings of Progressive Dairy Farmers Association of Ludhiana, Punjab, India. Ten dairy farms were randomly selected as per probability proportional to size and a total of 450 lactating HF crossbred cows were taken into the study. All the lactating cows were scored for locomotion and rear leg view index. Trimming was done in all the clinically lame animals (animals with locomotion scores 2 and 3) and equal number of animals selected randomly from those with locomotion scores 0 and 1. Various claw lesions were evaluated in both the groups. There was a significant relationship between locomotion score and rear leg view index to identify lameness. Sole ulcers and white line fissures were the lesions responsible for clinical lameness. Other lesions did not cause clinical lameness but increased the asymmetry in lactating HF crossbred cows. Both locomotion score and rear leg view index could be reliably used to identify clinical lameness in lactating cattle. PMID- 25133014 TI - Detection of circulating tumor cells. AB - The increasing number of treatment options for patients with metastatic carcinomas has created an accompanying need for methods to determine if the tumor will be responsive to the intended therapy and to monitor its effectiveness. Ideally, these methods would be noninvasive and provide quantitative real-time analysis of tumor activity in a variety of carcinomas. Assessment of circulating tumor cells shed into the blood during metastasis may satisfy this need. Here we review the CellSearch technology used for the detection of circulating tumor cells and discuss potential future directions for improvements. PMID- 25133015 TI - Biofilms and Helicobacter pylori: Dissemination and persistence within the environment and host. AB - The presence of viable Helicobacter pylori (H. pylori) in the environment is considered to contribute to the levels of H. pylori found in the human population, which also aids to increase its genetic variability and its environmental adaptability and persistence. H. pylori form biofilms both within the in vitro and in vivo environment. This represents an important attribute that assists the survival of this bacterium within environments that are both hostile and adverse to proliferation. It is the aim of this paper to review the ability of H. pylori to form biofilms in vivo and in vitro and to address the inherent mechanisms considered to significantly enhance its persistence within the host and in external environments. Furthermore, the dissemination of H. pylori in the external environment and within the human body and its impact upon infection control will be discussed. PMID- 25133016 TI - Role of Toll-like receptors in Helicobacter pylori infection and immunity. AB - The gram-negative bacterium Helicobacter pylori (H. pylori) infects the stomachs of approximately half of the world's population. Although infection induces an immune response that contributes to chronic gastric inflammation, the response is not sufficient to eliminate the bacterium. H. pylori infection causes peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Disease outcome is linked to the severity of the host inflammatory response. Gastric epithelial cells represent the first line of innate immune defence against H. pylori, and respond to infection by initiating numerous cell signalling cascades, resulting in cytokine induction and the subsequent recruitment of inflammatory cells to the gastric mucosa. Pathogen recognition receptors of the Toll-like receptor (TLR) family mediate many of these cell signalling events. This review discusses recent findings on the role of various TLRs in the recognition of H. pylori in distinct cell types, describes the TLRs responsible for the recognition of individual H. pylori components and outlines the influence of innate immune activation on the subsequent development of the adaptive immune response. The mechanistic identification of host mediators of H. pylori-induced pathogenesis has the potential to reveal drug targets and opportunities for therapeutic intervention or prevention of H. pylori-associated disease by means of vaccines or immunomodulatory therapy. PMID- 25133017 TI - Molecular mechanisms of alcohol associated pancreatitis. AB - Alcohol abuse is commonly associated with the development of both acute and chronic pancreatitis. Despite this close association, the fact that only a small percentage of human beings who abuse alcohol develop pancreatitis indicates that alcohol abuse alone is not sufficient to initiate clinical pancreatitis. This contention is further supported by the fact that administration of ethanol to experimental animals does not cause pancreatitis. Because of these findings, it is widely believed that ethanol sensitizes the pancreas to injury and additional factors trigger the development of overt pancreatitis. How ethanol sensitizes the pancreas to pancreatitis is not entirely known. Numerous studies have demonstrated that ethanol and its metabolites have a number of deleterious effects on acinar cells. Important acinar cells properties that are affected by ethanol include: calcium signaling, secretion of zymogens, autophagy, cellular regeneration, the unfolded protein response, and mitochondrial membrane integrity. In addition to the actions of ethanol on acinar cells, it is apparent that ethanol also affects pancreatic stellate cells. Pancreatic stellate cells have a critical role in normal tissue repair and the pathologic fibrotic response. Given that ethanol and its metabolites affect so many pancreatic functions, and that all of these effects occur simultaneously, it is likely that none of these effects is "THE" effect. Instead, it is most likely that the cumulative effect of ethanol on the pancreas predisposes the organ to pancreatitis. The focus of this article is to highlight some of the important mechanisms by which ethanol alters pancreatic functions and may predispose the pancreas to disease. PMID- 25133018 TI - Early phase of acute pancreatitis: Assessment and management. AB - Acute pancreatitis (AP) is a potentially life-threatening disease with a wide spectrum of severity. The overall mortality of AP is approximately 5%. According to the revised Atlanta classification system, AP can be classified as mild, moderate, or severe. Severe AP often takes a clinical course with two phases, an early and a late phase, which should both be considered separately. In this review article, we first discuss general aspects of AP, including incidence, pathophysiology, etiology, and grading of severity, then focus on the assessment of patients with suspected AP, including diagnosis and risk stratification, followed by the management of AP during the early phase, with special emphasis on fluid therapy, pain management, nutrition, and antibiotic prophylaxis. PMID- 25133019 TI - Potential role of NADPH oxidase in pathogenesis of pancreatitis. AB - Studies have demonstrated that reactive oxygen species (ROS) are closely related to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase (NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic cells. Besides directly producing the detrimental highly reactive ROS to act on biomolecules (lipids, proteins, and nucleic acids), NOX can also activate multiple signal transduction pathways, which regulate cell growth, proliferation, differentiation and apoptosis by producing ROS. Recently, research on pancreatic NOX is no longer limited to inflammatory cells, but extends to the aspect of pancreatic acinar cells and pancreatic stellate cells, which are considered to be potentially associated with pancreatitis. In this review, we summarize the literature on NOX protein structure, activation, function and its role in the pathogenesis of pancreatitis. PMID- 25133020 TI - Barrett's oesophagus: Evidence from the current meta-analyses. AB - Guidelines have been published regarding the management of Barrett's oesophagus (columnar-lined oesophagus). These have examined the role of surveillance in an effort to detect dysplasia and early cancer. The guidelines have provided criteria for enrolment into surveillance and some risk stratification with regard to surveillance interval. The research basis for the decisions reached with regard to cancer risk is weak and this manuscript has examined the available data published from meta-analyses up to 25(th) April 2013 (much of which has been published since the guidelines and their most recent updates have been written). There were 9 meta-analyses comparing patients with Barrett's oesophagus to control populations. These have demonstrated that Barrett's oesophagus is more common in males than females, in subjects who have ever smoked, in subjects with obesity, in subjects with prolonged symptoms of gastro-oesophageal reflux disease, in subjects who do not have infection with Helicobacter pylori and in subjects with hiatus hernia. These findings should inform public health measures in reducing the risk of Barrett's oesophagus and subsequent surveillance burden and cancer risk. There were 8 meta-analyses comparing different groups of patients with Barrett's oesophagus with regard to cancer risk. These have demonstrated that there was no statistically significant benefit of antireflux surgery over medical therapy, that endoscopic ablative therapy was effective in reducing cancer risk that there was similar cancer risk in patients with Barrett's oesophagus independent of geographic origin, that the adenocarcinoma incidence in males is twice the rate in females, that the cancer risk in long segment disease showed a trend to be higher than in short segment disease, that there was a trend for higher cancer risk in low-grade dysplasia over non dysplastic Barrett's oesophagus, that there is a lower risk in patients with Helicobacter pylori infection and that there is a significant protective effect of aspirin and statins. There were no meta-analyses examining the role of intestinal metaplasia. These results demonstrate that guidance regarding surveillance based on the presence of intestinal metaplasia, segment length and the presence of low-grade dysplasia has a weak basis, and further consideration should be given to gender and helicobacter status, ablation of the metaplastic segment as well as the chemoprotective role of aspirin and statins. PMID- 25133021 TI - Review to better understand the macroscopic subtypes and histogenesis of intrahepatic cholangiocarcinoma. AB - Intrahepatic cholangiocarcinoma is macroscopically classified into three subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth type. Each subtype should be preoperatively differentiated to perform the valid surgical resection. Recent researches have revealed the clinical, radiologic, pathobiological characteristics of each subtype. We reviewed recently published studies covering various aspects of intrahepatic cholangiocarcinoma (ICC), focusing especially on the macroscopic subtypes and stem cell features to better understand the pathophysiology of ICC and to establish the valid therapeutic strategy. PMID- 25133022 TI - Laparoscopic surgery in the management of Crohn's disease. AB - Crohn's disease is a chronic inflammatory bowel disease with surgery still frequently necessary in its treatment. Since the 1990's, laparoscopic surgery has become increasingly common for primary resections in patients with Crohn's disease and has now become the standard of care. Studies have shown no difference in recurrence rates when compared to open surgery and benefits include shorter hospital stay, lower rates of wound infection and decreased time to bowel function. This review highlights studies comparing the laparoscopic approach to the open approach in specific situations, including cases of complicated Crohn's disease. PMID- 25133023 TI - Pathophysiology of fistula formation in Crohn's disease. AB - Fistulae represent an important complication in patient suffering from Crohn's disease (CD). Cumulative incidence of fistula formation in CD patients is 17%-50% and about one third of patients suffer from recurring fistulae formation. Medical treatment options often fail and also surgery frequently is not successful. Available data indicate that CD-associated fistulae originate from an epithelial defect that may be caused by ongoing inflammation. Having undergone epithelial to mesenchymal transition (EMT), intestinal epithelial cells (IEC) penetrate into deeper layers of the mucosa and the gut wall causing localized tissue damage formation of a tube like structure and finally a connection to other organs or the body surface. EMT of IEC may be initially aimed to improve wound repair mechanisms since "conventional" wound healing mechanisms, such as migration of fibroblasts, are impaired in CD patients. EMT also enhances activation of matrix remodelling enzymes such as matrix metalloproteinase (MMP)-3 and MMP-9 causing further tissue damage and inflammation. Finally, soluble mediators like TNF and interleukin-13 further induce their own expression in an autocrine manner and enhance expression of molecules associated with cell invasiveness aggravating the process. Additionally, pathogen-associated molecular patterns also seem to play a role for induction of EMT and fistula development. Though current knowledge suggests a number of therapeutic options, new and more effective therapeutic approaches are urgently needed for patients suffering from CD-associated fistulae. A better understanding of the pathophysiology of fistula formation, however, is a prerequisite for the development of more efficacious medical anti fistula treatments. PMID- 25133024 TI - Escherichia coli in chronic inflammatory bowel diseases: An update on adherent invasive Escherichia coli pathogenicity. AB - Escherichia coli (E. coli), and particularly the adherent invasive E. coli (AIEC) pathotype, has been increasingly implicated in the ethiopathogenesis of Crohn's disease (CD). E. coli strains with similar pathogenic features to AIEC have been associated with other intestinal disorders such as ulcerative colitis, colorectal cancer, and coeliac disease, but AIEC prevalence in these diseases remains largely unexplored. Since AIEC was described one decade ago, substantial progress has been made in deciphering its mechanisms of pathogenicity. However, the molecular bases that characterize the phenotypic properties of this pathotype are still not well resolved. A review of studies focused on E. coli populations in inflammatory bowel disease (IBD) is presented here and we discuss about the putative role of this species on each IBD subtype. Given the relevance of AIEC in CD pathogenesis, we present the latest research findings concerning AIEC host microbe interactions and pathogenicity. We also review the existing data regarding the prevalence and abundance of AIEC in CD and its association with other intestinal diseases from humans and animals, in order to discuss the AIEC disease- and host-specificity. Finally, we highlight the fact that dietary components frequently found in industrialized countries may enhance AIEC colonization in the gut, which merits further investigation and the implementation of preventative measures. PMID- 25133025 TI - Similarities and differences between Behcet's disease and Crohn's disease. AB - Behcet's disease (BD) is a chronic inflammatory condition with multisystem involvement. Approximately 10%-15% of patients present with gastrointestinal involvement. Involved sites and the endoscopic view usually resemble Crohn's disease (CD). In addition to intestinal involvement, oral mucosa, the eyes, skin, and joints are commonly affected. No pathognomonic laboratory test is available for the diagnosis of either disease. Management approaches are also similar in various aspects. Differentiating BD from CD is highly challenging. In this article, the similarities and differences between BD and CD in terms of epidemiology, etiopathogenesis, clinical and imaging findings, and histopathological and therapeutic approaches are reviewed. PMID- 25133027 TI - Pancreatitis-imaging approach. AB - Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrast-enhanced computed tomography (MD-CECT) the most used imaging technique. However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI. PMID- 25133026 TI - Multidisciplinary and evidence-based management of fistulizing perianal Crohn's disease. AB - Perianal symptoms are common in patients with Crohn's disease and cause considerable morbidity. The etiology of these symptoms include skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal manifestation. Multiple treatment options exist although very few are evidence based. The phases of treatment include: drainage of infection, assessment of Crohn's disease status and fistula tracts, medical therapy, and selective operative management. The impact of biological therapy on perianal Crohn's disease is uncertain given that outcomes are conflicting. Operative treatment to eradicate the fistula tract can be attempted once infection has resolved and Crohn's disease activity is controlled. The operative approach should be tailored according to the anatomy of the fistula tract. Definitive treatment is challenging with medical and operative treatment rarely leading to true healing with frequent complications and recurrence. Treatment success must be weighed against the risk of complications, specially anal sphincter injury. A full understanding of the etiology and all potential therapeutic options is critical for success. Multidisciplinary management of fistulizing perianal Crohn's disease is crucial to improve outcomes. PMID- 25133029 TI - Role of hemostatic powders in the endoscopic management of gastrointestinal bleeding. AB - Acute gastrointestinal bleeding (AGIB) is a prevalent condition with significant influence on healthcare costs. Endoscopy is essential for the management of AGIB with a pivotal role in diagnosis, risk stratification and management. Recently, hemostatic powders have been added to our endoscopic armamentarium to treat gastrointestinal (GI) bleeding. These substances are intended to control active bleeding by delivering a powdered product over the bleeding site that forms a solid matrix with a tamponade function. Local activation of platelet aggregation and coagulation cascade may be also boosted. There are currently three powders commercially available: hemostatic agent TC-325 (Hemospray((r))), EndoClotTM polysaccharide hemostatic system, and Ankaferd Bloodstopper((r)). Although the available evidence is based on short series of cases and there is no randomized controlled trial yet, these powders seem to be effective in controlling GI bleeding from a variety of origins with a very favorable side effects profile. They can be used either as a primary therapy or a second-line treatment, and they seem to be especially indicated in cases of cancer-related bleeding and lesions with difficult access. In this review, we will comment on the mechanism of action, efficacy, safety and technical challenges of the use of powders in several clinical scenarios and we will try to define the main current indications of use and propose new lines of research in this area. PMID- 25133028 TI - New insights to occult gastrointestinal bleeding: From pathophysiology to therapeutics. AB - Obscure gastrointestinal bleeding is still a clinical challenge for gastroenterologists. The recent development of novel technologies for the diagnosis and treatment of different bleeding causes has allowed a better management of patients, but it also determines the need of a deeper comprehension of pathophysiology and the analysis of local expertise in order to develop a rational management algorithm. Obscure gastrointestinal bleeding can be divided in occult, when a positive occult blood fecal test is the main manifestation, and overt, when external sings of bleeding are visible. In this paper we are going to focus on overt gastrointestinal bleeding, describing the physiopathology of the most usual causes, analyzing the diagnostic procedures available, from the most classical to the novel ones, and establishing a standard algorithm which can be adapted depending on the local expertise or availability. Finally, we will review the main therapeutic options for this complex and not so uncommon clinical problem. PMID- 25133030 TI - Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis. AB - Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve (primary non-response) or lose response after a period of improvement (secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters that may predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular (immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy. PMID- 25133032 TI - Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer. AB - Neoadjuvant therapy has been proven to be extremely valuable and is widely used for advanced esophageal cancer. However, a significant proportion of treated patients (60%-70%) does not respond well to neoadjuvant treatments and develop severe adverse effects. Therefore, predictive markers for individualization of multimodality treatments are urgently needed in esophageal cancer. Recently, molecular biomarkers that predict the response to neoadjuvant therapy have been explored in multimodal approaches in esophageal cancer and successful examples of biomarker identification have been reported. In this review, promising candidates for predictive molecular biomarkers developed by using multiple molecular approaches are reviewed. Moreover, treatment strategies based on the status of predicted biomarkers are discussed, while considering the international differences in the clinical background. However, in the absence of adequate treatment options related to the results of the biomarker test, the usefulness of these diagnostic tools is limited and new effective therapies for biomarker identified nonresponders to cancer treatment should be concurrent with the progress of predictive technologies. Further improvement in the prognosis of esophageal cancer patients can be achieved through the introduction of novel therapeutic approaches in clinical practice. PMID- 25133033 TI - Epidemiological studies of esophageal cancer in the era of genome-wide association studies. AB - Esophageal cancer (EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type (90% 95%), while the incidence of esophageal adenocarcinoma (EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved in the process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies (GWAS). Here we review the epidemiological studies of EC (especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants (genes, SNPs, miRNAs, proteins) involved in the process of ESCC. PMID- 25133031 TI - Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature. AB - Ulcerative colitis (UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammation-related genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility. PMID- 25133035 TI - Helicobacter pylori as a risk factor for central serous chorioretinopathy: Literature review. AB - Helicobacter pylori (H. pylori), a Gram-negative bacterium, is one of the most frequent causes of gastrointestinal infections worldwide. It has been associated as a pathogen for the human body with many systemic diseases, including different eye diseases. We will focus on a specific eye disease called idiopathic central serous chorioretinopathy (ICSCR). This disease is characterized by a serous detachment of the neurosensory retina in the macular region, which affects the vision to different degrees. Currently, the pathophysiology of ICSCR is not clear and there is no effective treatment. However, several potential risk factors have been elucidated. One of the factors that has more frequently been associated with ICSCR is stress. As H. pylori was identified as a possible etiological factor for occlusive arterial diseases in young people who were particularly stressed, it was thought that H. pylori might also be present in ICSCR. Therefore, some physicians started to test its presence in patents with ICSCR. If H. pylori happened to be associated with ICSCR, the treatment of gastrointestinal infection could also improve visual symptoms and help to remediate this eye disease. Although H. pylori is highly prevalent in the general population, a true correlation seems to exist. We present a review on the relationship between ICSCR and H. pylori. PMID- 25133034 TI - Perihilar cholangiocarcinoma: Current therapy. AB - Perihilar cholangiocarcinoma, which is a rare primary malignancy, originates from the epithelial cells of the bile duct. Usually invading the periductal tissues and the lymph nodes, perihilar cholangiocarcinoma is commonly diagnosed in the advanced stage of the disease and has a dismal prognosis. Currently, complete hepatectomy is the primary therapy for curing this disease. Perioperative assessment and available surgical procedures can be considered for achieving a negative margin resection, which is associated with long-term survival and better quality of life. For patients with unresectable cholangiocarcinoma, several palliative treatments have been demonstrated to produce a better outcome; and liver transplantation for selected patients with perihilar cholangiocarcinoma is promising and desirable. However, the role of palliative treatments and liver transplantation was controversial and requires more evidence and substantial validity from multiple institutions. In this article, we summarize the data from multiple institutions and discuss the resectability, mortality, morbidity and outcome with different approaches. PMID- 25133036 TI - Risk of cardiovascular disease in inflammatory bowel disease. AB - Abundant scientific evidence supporting an association between inflammatory bowel disease (IBD) and venous thromboembolic events, caused by an IBD related hypercoagulability, is acknowledged and thromboprophylactic treatment strategies are now implemented in the management of IBD patients. In contrary, the risk of arterial thromboembolic disease, as ischemic heart disease, cerebrovascular events, and mesenteric ischemia in patients with IBD remains uncertain and the magnitude of a potentially increased risk is continuously debated, with ambiguous risk estimates among studies. The evident role of inflammation in the pathogenesis of atherosclerosis forms the basis of a biological plausible link; the chronic systemic inflammation in IBD patients increases the risk of atherosclerosis and thereby the risk of thrombotic events. Further, studies have shown that the burden of traditional risk factors for atherosclerosis, such as obesity, diabetes mellitus, and dyslipidemia is lower in IBD populations, thus further strengthen the role of non-traditional risk factors, as chronic inflammation in the linking of the two disease entities. Likewise, mortality from cardiovascular disease in IBD remains questioned. The aim of the current review is to give an up-date on the existing evidence of the possible association between IBD and cardiovascular disease and to discuss traditional and non traditional risk factors. PMID- 25133037 TI - Cancer stem cells in Helicobacter pylori infection and aging: Implications for gastric carcinogenesis. AB - AIM: To demonstrated the combined effects of aging and carcinogen treatment on cancer stem/stem-like cells (CSCs) of gastric mucosa in an animal model. METHODS: In this study we investigated the effects of aging and Helicobacter pylori (H. pylori) inflammation as a model for inflammation induced carcinogenesis in human and rat gastric mucosa samples. In aging studies, we compared 4-mo old (young) with 22 mo (aged) old Fischer-344 rats. For human studies, gastric biopsies and resection specimens representing normal mucosa or different stages of H. pylori gastritis and gastric adenocarcinomas were used for determining the expression of stem cell markers CD166, ALDH1 and LGR5. In addition we performed immunofluorescent double labeling for B-catenin and Lgr5 in both rat and human gastric tissues to examine the status of Wnt signaling in these cells. RESULTS: CSC markers ALDH1, LGR5, and CD166 were expressed in very low levels in normal human gastric mucosa or young rat gastric mucosa. In contrast, level of expression for all three markers significantly increased in H. pylori gastritis and gastric adenocarcinomas as well as in normal gastric mucosa in aged rats. We also observed cytoplasmic B-catenin staining in both aged rat and human H. pylori inflamed gastric mucosa, which were found to be colocalized with Lgr5 immunoreactive cells. The increased number of ALDH1, CD166 and LGR5 positive cells in H. pylori gastritis indicates that increased number of stem-like cells in gastric mucosa is an early event, and may constitute an important step in the progression to neoplasia. CONCLUSION: Our observation of the age-related increase in cancer stem/stem-like cells in the gastric mucosa may explain the increased incidence of gastric cancer during aging. Combination of aging and H. pylori infection may have additive effects in progression to neoplasia. PMID- 25133038 TI - Oxidative and nitrosative stress enzymes in relation to nitrotyrosine in Helicobacter pylori-infected humans. AB - AIM: To compare a possible relation between Helicobacter pylori (H. pylori) and the oxygen- and nitrogen radical system in humans. METHODS: Mechanisms for H. pylori to interfere with the oxygen and nitrogen radical system is of great importance for understanding of the H. pylori persistence and pathogenesis. Biopsies were obtained from the gastric wall of 21 individuals. Ongoing infection with H. pylori was detected using direct analyze from the biopsies using campylobacter-like organism test (CLO-test) and/or by using (14)C-urea breath test. The individuals were divided in a negative H. pylori and a positive H. pylori group. Expression in the gastric mucosa of inducible nitric oxide syntase (iNOS), nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase) myeloperoxidase (MPO), and nitrotyrosine were assessed by Western blotting. RESULTS: The individuals who undervent gastroscopy were divided in a H. pylori neg. [n = 13, m/f = 7/6, age (mean) = 39] and a H. pylori pos. group [n= 8, m/f = 5/3, age (mean) = 53]. Using western blot analysis iNOS was detected as a 130 kDa band. The iNOS expression was upregulated in the antrum of H. pylori infected individuals in comparison to the controls, mean +/- SD being 12.6 +/- 2.4 vs 8.3 +/- 3.1, P < 0.01. There was a markedly upregulated expression of MPO in the antrum of H. pylori infected individuals in comparison to the control group without infection. In several of non-infected controls it was not possible to detect any MPO expression at all, whereas the expression was high in all the infected subjects, mean +/- SD being 5.1 +/- 3.4 vs 2.1 +/- 1.9, P < 0.05. The NADPH-oxidase expression was analysed by detecting the NADPH-oxidase subunit p47 phox expression. P47-phox was detected as a 47 kDa band using Western blot, and showed a significantly higher expression of p47-phox in the antrum of the H. pylori infected individuals compared to the controls, mean +/- SD being 3.1 +/- 2.2 vs 0.3 +/- 0.2, P < 0.01. Regarding nitrotyrosine formation, Western blot did not show any significant increase or decrease compared to controls, 7.0 +/- 0.9 vs 6.9 +/- 1.1, not significant. CONCLUSION: iNOS, MPO and NADPH-oxidase was up regulated among H. pylori infected. Regarding nitrotyrosine no difference was found. This support an H. pylori related inhibition of radical formation. PMID- 25133039 TI - Diagnosis and treatment of gastroesophageal reflux disease. AB - Gastroesophageal reflux disease (GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical, atypical and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms, these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations, further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis, peptic stricture, Barrett's esophagus, esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification, medical therapy and surgical therapy. Lifestyle modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids, histamine-receptor antagonists or proton pump inhibitors. Whereas most patients can be effectively managed with medical therapy, others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gastroesophageal reflux disease. PMID- 25133040 TI - Use of methotrexate in inflammatory bowel disease in 2014: A User's Guide. AB - Methotrexate has been used an immunomodulator in many autoimmune diseases, including inflammatory bowel disease. However, many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios: (1) steroid dependant Crohn's disease (CD); (2) maintenance of remission in steroid free CD; (3) azathioprine failures in CD; (4) in combination therapy with Anti TNF agents in CD; (5) decreasing antibody formation to Anti-TNF therapy in CD; (6) management of fistulizing disease in CD; and (7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients. PMID- 25133042 TI - Approach to Helicobacter pylori infection in geriatric population. AB - The prevalence of Helicobacter pylori (H. pylori) infection and its complications increase with age. The majority of infected individuals remain asymptomatic throughout the life but 10%-20% develops peptic ulcer disease and 1% gastric malignancies. The incidence of ulcers and their complications are more common in the older population resulting in higher hospitalization and mortality rates. The increased use of medications causing gastric mucosal damage and the decreased secretion of protective prostaglandins in elderly are major factors increasing gastric mucosal sensitivity to the destructive effects of H. pylori. Due to higher prevalence of gastrointestinal (GI) malignancies, upper GI endoscopy is mostly preferred in elderly for the diagnosis of infection. Therefore, "endoscopy and treat" strategy may be more appropriate instead of "test and treat" strategy for dyspeptic patients in older age. Urea breath test and stool antigen test can be used for control of eradication, except for special cases requiring follow-up with endoscopy. The indications for treatment and suggested eradication regimens are similar with other age groups; however, the eradication failure may be a more significant problem due to high antibiotic resistance and low compliance rate in elderly. Multidrug usage and drug interactions should always be considered before starting the treatment. This paper reviews briefly the epidemiology, diagnosis, disease manifestations, and treatment options of H. pylori in the geriatric population. PMID- 25133043 TI - Pharmacological therapy of feed intolerance in the critically ills. AB - Feed intolerance in the setting of critical illness is associated with higher morbidity and mortality, and thus requires promptly and effective treatment. Prokinetic agents are currently considered as the first-line therapy given issues relating to parenteral nutrition and post-pyloric placement. Currently, the agents of choice are erythromycin and metoclopramide, either alone or in combination, which are highly effective with relatively low incidence of cardiac, hemodynamic or neurological adverse effects. Diarrhea, however, can occur in up to 49% of patients who are treated with the dual prokinetic therapy, which is not associated with Clostridium difficile infection and settled soon after the cessation of the drugs. Hence, the use of prokinetic therapy over a long period or for prophylactic purpose must be avoided, and the indication for ongoing use of the drug(s) must be reviewed frequently. Second line therapy, such as total parenteral nutrition and post-pyloric feeding, must be considered once adverse effects relating the prokinetic therapy develop. PMID- 25133045 TI - Inflammatory bowel diseases: Current problems and future tasks. AB - Current knowledge on inflammatory bowel disease (IBD) is mainly endorsed by controlled trials and epidemiologic studies. Yet, we seldom look at the messages from real-world practice. Among a patient population followed since 2008, we looked at an unselected sample of 64 IBD patients [26 Crohn's disease (CD) and 38 ulcerative colitis (UC)] who had been seen as out-patients in the last year. Inducing remission, mesalamines (86% for UC/69% for CD/33%-16% as MMX formulation) prevailed as prescriptions; steroids (55%/19% for UC/CD) ranked second. Prescription of third-party drugs (antibiotics, NSAIDs, biologics) and adherence, were issues in the maintenance. 34% of CD, and 23% of UC patients showed accompanying immunologic diseases: CD-associated familiar psoriasis (4:9) ranked first. Main Message. The association between IBD (CD mainly) and psoriasis, now found in our practice, matches current basic science gathering IBD together with psoriasis (and perhaps chronic respiratory disease) under the comprehensive term "barrier organ disease" wherein an epithelial surface with sensor systems rules contacts between outer antigens and a reactive underneath tissue, with the balance between inflammation and quiescence kept at any time by mucosal permeability. IBD is thus viewed as a polyfactorial/polygenic/syndromic disorder, embedded into a galaxy of immune conditions offering multiple points of attack. This mindset of splitting the IBDs into pathogenic categories may allow overcoming the uniformly targeting of a single cytokine by biological drugs, in favor of demarcating the boundaries between different disease-subtype-specific indications, and paving the way to future personalized strategies. PMID- 25133041 TI - Visceral hypersensitivity and electromechanical dysfunction as therapeutic targets in pediatric functional dyspepsia. AB - Functional gastrointestinal disorders (FGID) are common clinical syndromes diagnosed in the absence of biochemical, structural, or metabolic abnormalities. They account for significant morbidity and health care expenditures and are identifiable across variable age, geography, and culture. Etiology of abdominal pain associated FGIDs, including functional dyspepsia (FD), remains incompletely understood, but growing evidence implicates the importance of visceral hypersensitivity and electromechanical dysfunction. This manuscript explores data supporting the role of visceral hypersensitivity and electromechanical dysfunction in FD, with focus on pediatric data when available, and provides a summary of potential therapeutic targets. PMID- 25133044 TI - Renal dysfunction in patients with cirrhosis: Where do we stand? AB - Patients with cirrhosis and renal failure are high-risk patients who can hardly be grouped to form precise instructions for diagnosis and treatment. When it comes to evaluate renal function in patients with cirrhosis, determination of acute kidney injury (AKI), chronic kidney disease (CKD) or AKI on CKD should be made. First it should be excluded the prerenal causes of AKI. All cirrhotic patients should undergo renal ultrasound for measurement of renal resistive index in every stage of liver dysfunction and urine microscopy for differentiation of all causes of AKI. If there is history of dehydration on the ground of normal renal ultrasound and urine microscopy the diuretics should be withdrawn and plasma volume expansion should be tried with albumin. If the patient does not respond, the correct diagnosis is HRS. In case there is recent use of nephrotoxic agents or contrast media and examination shows shock, granular cast in urinary sediment and proteinuria above 0.5 g daily, acute tubular necrosis is the prominent diagnosis. Renal biopsy should be performed when glomerular filtration rate is between 30-60 mL/min and there are signs of parenchymal renal disease. The acute renal function is preferable to be assessed with modified AKIN. Patients with AKIN stage 1 and serum creatinine >= 1.5 mg/dL should be at close surveillance. Management options include hemodynamic monitoring and management of fluid balance and infections, potentially driving to HRS. Terlipressin is the treatment of choice in case of established HRS, administered until there are signs of improvement, but not more than two weeks. Midodrine is the alternative for therapy continuation or when terlipressin is unavailable. Norepinephrine has shown similar effect with terlipressin in patients being in Intensive Care Unit, but with much lower cost than that of terlipressin. If the patient meets the requirements for transplantation, dialysis and transjugular intrahepatic portosystemic shunt are the bridging therapies to keep the transplant candidate in the best clinical status. The present review clarifies the latest therapeutic modalities and the proposed recommendations and algorithms in order to be applied in clinical practice. PMID- 25133046 TI - Prevention of hepatocellular carcinoma in patients with chronic hepatitis B. AB - Patients with chronic hepatitis B are at significant risk for hepatocellular carcinoma (HCC). Globally, over half a million people each year are diagnosed with HCC, with marked geographical variations. Despite overwhelming evidence for a causal role of hepatitis B virus (HBV) infection in the development of HCC and a well-established relationship between high baseline hepatitis B viral load and cumulative risk of HCC, the molecular basis for this association has not been fully elucidated. In addition, a beneficial role for antiviral therapy in preventing the development of HCC has been difficult to establish. This review examines the biological and molecular mechanisms of HBV-related hepatocarcinogenesis, recent results on the effect of modern nucleos(t)ides on the rate of HCC development in high risk HBV cohorts and the potential mechanisms by which long-term antiviral therapy with potent inhibitors of HBV replication might reduce the risk of HCC in patients with chronic hepatitis B. Although evidence from randomized controlled trials shows the favourable effects of antiviral agents in achieving profound and durable suppression of HBV DNA levels while improving liver function and histology, robust evidence of other long-term clinical outcomes, such as prevention of HCC, are limited. PMID- 25133047 TI - Ischemic heart disease, factor predisposing to Barrett's adenocarcinoma: A case control study. AB - AIM: To define the significance of ischemic heart disease (IHD) (stable angina to infarction) co-existance in Barrett esophagus (BE) patients and patients with esophageal adenocarcinoma (AdE). METHODS: All BE/AdE patients in Blackpool-Wyre Fylde area and Trikala prefecture identified from medical records. Patient clinical details were obtained from hospital and General Practitioner records. Additional information was gathered from validated questionnaire. RESULTS: Forty (33%) AdE and 83 (19%) BE patients had IHD (P = 0.002). Eighteen (15%) AdE and 34 (8%) BE patients had suffered a myocardial infarction (P = 0.03). Three (3%) AdE and 7 (2%) BE patients had severe heart failure (P = 0.82). Thirty-nine (47%) BE with IHD and 8 (20%) AdE patients with IHD consumed aspirin daily (P = 0.004). Seventh-seven (93%) BE patients with IHD and 36 (90%) AdE patients with IHD were on statins (P = 0.86). Logistic regression analysis: AdE was more frequent in the elderly, with long term reflux, long BE and concurrent IHD (odds ratio: 2.086, P = 0.001) not consuming statins. Eighteen (22%) BE patients with IHD [16 (84%) with myocardial infarction] vs 33 (10%) without IHD died from non-neoplastic causes within 24 mo from BE diagnosis (P = 0.005). CONCLUSION: IHD is more prevalent in AdE than BE patients. Increased prevalence of AdE is related with the presence of myocardial infarction but not severe heart failure, possibly because patients with BE and severe IHD have low life expectancy. PMID- 25133048 TI - Statins and their role in acute pancreatitis: Case report and literature review. AB - Statin induced pancreatitis has historically been considered a diagnosis of exclusion, with literature references typically in the form of case reports and observational studies. Recently, larger studies have challenged the correlations made by earlier case reports, and instead demonstrate a mild protective effect in statin users. We present a case report of likely statin induced pancreatitis in a 58-year-old male (which we have attributed to drug-drug interaction with resulting inhibition of hepatic cytochrome P450 enzymes) and have reviewed the apparent dichotomy in the available literature. PMID- 25133049 TI - Rhabdomyolysis after midazolam administration in a cirrhotic patient treated with atorvastatin. AB - The administration of statins in patients with liver disease is not an absolute contraindication. Hepatotoxicity is a rare and often dose-related event and in the literature there are only a few described cases of fatal rhabdomyolysis in patients with chronic liver disease after statin administration. During treatment with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, the factors responsible for myopathy may either be related to the patient, or due to interactions with other medications that are metabolic substrates of the same isozymes and therefore able to increase blood statin concentration. The most important side effects consist of increased transaminase levels, abdominal pain or muscle weakness, increased serum levels of creatine kinase and rhabdomyolysis. In this article we report a case of fatal rhabdomyolysis with acute renal failure after gastric endoscopy, where midazolam was used as a sedation agent in a patient with chronic liver disease treated with a high dose of atorvastatin. Therefore, we suggest paying particular attention to the potential risks of associating atorvastatin and midazolam in patients with chronic liver disease who need to undergo gastric endoscopy. PMID- 25133050 TI - Can primary care sleep medicine integration work? AB - Sleep disorders are common in the veteran population. There is an increasing need for sleep medicine services in returning veterans. Primary care providers are uncomfortable diagnosing and treating sleep disorders. Patients often have to wait several days before they can be seen by a sleep clinician. This pilot project evaluated the feasibility of providing sleep medicine services to patients in a primary care setting. Primary care providers were involved in decision-making, resulting in improved satisfaction with sleep medicine services among primary care clinicians. PMID- 25133051 TI - Negative rumor: contagion of a psychiatric department. AB - Over the past few decades, a sizable body of literature on the effects of rumors and gossip has emerged. Addressing rumors in the workplace is an important subject, as rumors have a direct impact on the quality of the work environment and also on the productivity and creativity of the employees. To date, little has been written on the effect of rumors and gossip in psychiatric hospitals. This article presents case vignettes of rumors spread in psychiatric hospitals and the impact on team cohesion and morale among the staff implicated in these, too often, neglected occurrences. Dynamic aspects with particular focus on rumors in psychiatric units and suggestions for remedy and treatment are presented. PMID- 25133053 TI - Lithium-induced fixed drug eruption in a case of bipolar mania. PMID- 25133054 TI - DSM-5 Drops the 5 Axes of Mysticism: A Supportive Survey. PMID- 25133052 TI - Psychotic disorders in children and adolescents: a primer on contemporary evaluation and management. PMID- 25133055 TI - Lithium-induced transient euthyroid hyperthyroxinemia: a case report. PMID- 25133056 TI - A new perspective on gender dysphoria and repetitive sex reassignment surgeries: a case report. PMID- 25133057 TI - Secondary psychosis 3 months prior to the overt symptoms of multiple myeloma: a case report. PMID- 25133058 TI - A case report of the use of vilazodone in pregnancy. PMID- 25133059 TI - Nystagmus as a discontinuation symptom after antidepressant therapy: a case report. PMID- 25133060 TI - A survey of patients' knowledge about lithium therapy in the elderly. AB - OBJECTIVE: Lithium is commonly used in the treatment of various psychiatric disorders. It has a narrow therapeutic range and a mortality rate of 9% in patients intoxicated during maintenance therapy. Therefore, for lithium to be prescribed safely, clinicians must ensure that patients are aware of features of lithium toxicity. We aim to identify patients' knowledge of lithium in the elderly population and associated factors that may influence this knowledge. METHOD: The Lithium Knowledge Test (LKT) is a brief questionnaire that was developed as a means of identifying patients' practical and pharmacologic knowledge, which is important if therapy is to be safe and effective. The survey was conducted in the outpatient service of the Department of Old Age Psychiatry attached to a university teaching hospital in an urban area in Ireland between January 2011 and July 2011. A total of 33 patients participated in the survey, and the LKT questionnaires were completed by all participants. The LKT scores are obtained by adding up the responses to the questions, while the LKT hazard scores are obtained by adding together the responses to the questions on symptoms of toxicity. The result was analyzed using SPSS version 20 (SPSS Inc, Chicago, Illinois), and the relationships between LKT scores and LKT hazard scores as well as other variables were examined using Pearson's correlation coefficient. RESULTS: The mean LKT score of our sample population was 4.45, suggestive of poor knowledge of lithium, and the mean LKT hazard score was 5.85, highly suggestive of potentially hazardous lack of knowledge. There was a significant negative correlation between the LKT score and hazard score (r = -0.65, P < .01 [1 tailed]). CONCLUSIONS: The survey results highlight the need for patients to be given comprehensive information about lithium prior to commencement of treatment and a refresher educational program during lithium therapy. PMID- 25133061 TI - Association of hypnotics with stroke risk: a population-based case-control study. AB - BACKGROUND: The aim of this study was to determine what association, if any, hypnotics have on the risk of stroke events. METHOD: In a nationwide population based case-control study, cases were patients with incident stroke diagnosed between January 1, 2006, and December 31, 2006. Patients with hemorrhagic or ischemic stroke diagnosis codes (ICD-9-CM codes 430-438) and who had been hospitalized for further treatment were included in the study. Patients with any type of stroke diagnosed before 2006 were excluded. The authors selected 2,779 stroke patients and 27,790 controls matched for age, gender, physician visit date, and comorbidities. The impact of hypnotics on stroke was examined by multiple logistic regression models and sensitivity analyses. RESULTS: Individuals prescribed any hypnotic had elevated risk of stroke compared to those prescribed no hypnotics. For groups prescribed 1-27, 28-148, and >= 149 pills, odds ratios for stroke were 1.71 (95% CI, 1.49-1.96), 1.84 (95% CI, 1.62-2.11), and 1.45 (95% CI, 1.26-1.68), respectively. Adjusted odds ratios were elevated in separate analyses for zolpidem and estazolam. The observed results were robust with stratification by comorbidities, such as hypertension and diabetes, and using ischemic stroke as the case group. CONCLUSIONS: This study shows that, in a case-control study matched for age, gender, and comorbidities using multiple logistic regression and sensitivity tests, zolpidem and estazolam were slightly associated with an increased risk of stroke. Further large-scale and in-depth studies should be performed. Use of hypnotics should always be determined by specialists, and adverse effects should be continuously monitored. PMID- 25133062 TI - Acute interventions and referral of patients with bipolar disorder by the psychiatric consultation liaison service in a general hospital in Germany: a retrospective analysis. AB - OBJECTIVE: To investigate the population of bipolar patients in a general hospital in Germany who required treatment by a consultant psychiatrist. METHOD: A retrospective analysis was conducted of the clinical records of 47 patients diagnosed with bipolar disorder (DSM-IV-TR criteria) who were treated by a consultant psychiatrist between 2009 and 2012 in one of the general hospitals of Charite Berlin, Campus Benjamin Franklin, Berlin, Germany. We investigated the sections of the hospital that requested psychiatric consultations for bipolar patients, the status of these patients, and their primary cause of treatment, as well as the intervention (including pharmacotherapy) recommended by the consultant psychiatrist. RESULTS: For more than half of the patients, their psychiatric illness was either directly or indirectly the reason they presented to the hospital. The remaining bipolar patients were treated for various somatic illnesses unrelated to their bipolar disorder throughout the hospital, with a relative overrepresentation of patients in the neurology department. More than half of the patients were referred to a psychiatric hospital by the consultant psychiatrist. Benzodiazepines were the most commonly administered drugs for acute pharmacologic intervention. CONCLUSIONS: Psychiatric consultations are not frequently requested for bipolar patients compared to those with other psychiatric disorders. However, more than half of the bipolar patients needed further psychiatric treatment in a psychiatric hospital. This finding emphasizes the importance of psychiatric consultations in a general hospital for bipolar patients. The administration of benzodiazepines as an acute treatment seems to be the standard pharmacologic procedure, not a specific pharmacotherapy like mood stabilizers. PMID- 25133063 TI - Mixed Specifier for Bipolar Mania and Depression: Highlights of DSM-5 Changes and Implications for Diagnosis and Treatment in Primary Care. AB - Bipolar disorder, while commonly encountered in the primary care setting, is often misdiagnosed or undiagnosed. In the DSM-IV-TR, patients could be diagnosed as being in a mixed state only if they had concurrent manic and depressive symptoms; while this occurs in some patients, many more experience subsyndromal mixed symptoms that would disqualify a "mixed state" diagnosis. The recently released DSM-5 attempts to capture this large proportion of patients with subsyndromal mixed symptoms with the inclusion of the "mixed specifier." The presence of such subsyndromal mixed symptoms has significant implications for both diagnosis and treatment. For those presenting with major depressive disorder with subsyndromal manic symptoms, clinicians must be vigilant for the development of full-blown bipolar disease. In treating this group, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors remain first line therapy, but augmentation with other therapies is often required. If a diagnosis of bipolar disorder is confirmed and the patient is experiencing a depressive phase, traditional antidepressants should be avoided. For those presenting with mania and mixed depressive symptoms, treatment with a combination of atypical antipsychotics and mood stabilizers is best. PMID- 25133064 TI - Coping with helplessness. PMID- 25133065 TI - Multimedia Informed Consent Tool for a Low Literacy African Research Population: Development and Pilot-Testing. AB - BACKGROUND: International guidelines recommend the use of appropriate informed consent procedures in low literacy research settings because written information is not known to guarantee comprehension of study information. OBJECTIVES: This study developed and evaluated a multimedia informed consent tool for people with low literacy in an area where a malaria treatment trial was being planned in The Gambia. METHODS: We developed the informed consent document of the malaria treatment trial into a multimedia tool integrating video, animations and audio narrations in three major Gambian languages. Acceptability and ease of use of the multimedia tool were assessed using quantitative and qualitative methods. In two separate visits, the participants' comprehension of the study information was measured by using a validated digitised audio questionnaire. RESULTS: The majority of participants (70%) reported that the multimedia tool was clear and easy to understand. Participants had high scores on the domains of adverse events/risk, voluntary participation, study procedures while lowest scores were recorded on the question items on randomisation. The differences in mean scores for participants' 'recall' and 'understanding' between first and second visits were statistically significant (F (1,41)=25.38, p<0.00001 and (F (1, 41) = 31.61, p<0.00001 respectively. CONCLUSIONS: Our locally developed multimedia tool was acceptable and easy to administer among low literacy participants in The Gambia. It also proved to be effective in delivering and sustaining comprehension of study information across a diverse group of participants. Additional research is needed to compare the tool to the traditional consent interview, both in The Gambia and in other sub-Saharan settings. PMID- 25133066 TI - Microbial Infection and Rheumatoid Arthritis. AB - Rheumatoid arthritis (RA) is a complex autoimmune disease affecting 1-2% of general worldwide population. The etiopathogenesis of RA involves the interplay of multiple genetic risk factors and environmental triggers. Microbial infections are believed to play an important role in the initiation and perpetuation of RA. Recent clinical studies have shown the association of microbial infections with RA. Accumulated studies using animal models have also found that microbial infections can induce and/or exaggerate the symptoms of experimental arthritis. In this review, we have identified the most common microbial infections associated with RA in the literature and summarized the current evidence supporting their pathogenic role in RA. We also discussed the potential mechanisms whereby infection may promote the development of RA, such as generation of neo-autoantigens, induction of loss of tolerance by molecular mimicry, and bystander activation of the immune system. PMID- 25133067 TI - Astrocyte Reactivity: A Biomarker for Retinal Ganglion Cell Health in Retinal Neurodegeneration. AB - Retinal ganglion cell (RGC) loss in glaucoma is sectorial in nature and preceded by deficits in axonal transport. Neuroinflammation plays an important role in the pathophysiology of glaucoma in the retina, optic nerve and visual centers of the brain, where it similarly appears to be regulated spatially. In a murine model, we examined the spatial characteristics of astrocyte reactivity (migration/proliferation, hypertrophy and GFAP expression) in healthy retina, retina with two glaucoma-related risk factors (aging and genetic predisposition) and glaucomatous retina and established relationships between these reactivity indices and the spatial organization of astrocytes as well as RGC health. Astrocyte reactivity was quantified by morphological techniques and RGC health was determined by uptake and transport of the neural tracer cholera toxin beta subunit (CTB). We found that: (1) astrocyte reactivity occurs in microdomains throughout glaucomatous retina as well as retina with risk factors for glaucoma, (2) these astrocyte microdomains are primarily differentiated by the degree of retinal area covered by the astrocytes within them and (3) percent retinal area covered by astrocytes is highly predictive of RGC health. Our findings suggest that microdomains of astrocyte reactivity are biomarkers for functional decline of RGCs. Based on current and emerging imaging technologies, diagnostic assessment of astrocytes in the nerve fiber layer could succeed in translating axonal transport deficits to a feasible clinical application. PMID- 25133069 TI - Elevating quality with manditory use of standard reporting guidelines. AB - The Editorial staff of The International Journal of Sports Physical Therapy (IJSPT) is dedicated to the review, critical appraisal, and publication of high quality scientific and clinical research, systematic reviews, meta-analyses, and case reports. As IJSPT progresses through its' ninth year of providing high quality research evidence as well as relevant clinical commentary and suggestions for the international sports physical therapy community, we offer the following editorial. We, along with many other prestigious journals are committed to elevating the quality of published research related to disability and rehabilitation and agree to adherence to the following reporting guidelines, which will be required by IJSPT as of January 1, 2015. Many of these guidelines are all ready in place and have been implemented by IJSPT. This Editorial is a reprint of a previously published Editorial in The Archives of Physical Medicine and Rehabilitation, and is used with permission. (http://dx.doi.org/10.1016/j.apmr.2013.12.010) FOR CITATION PURPOSES, PLEASE USE THE ORIGINAL PUBLICATION DETAILS: Chan L, Heinemann AW, and Roberts J, Elevating the Quality of Disability and Rehabilitation Research: Mandatory use of the Reporting Guidelines. Archives of Physical Medicine and Rehabilitation, 2014: 95: 414-417. PMID- 25133068 TI - The Pathogenesis of Lupus Nephritis. AB - Lupus nephritis is a serious potential feature of systemic lupus erythematous (SLE). Though SLE typically cycles through periods of flares and remission, patients often eventually succumb to end-stage kidney or cardiovascular damage. This review of the pathogenesis of lupus nephritis examines the role of the complement cascade; the significance of autoantibodies, the breaking of tolerance, and the implications of altered apoptosis in breaking tolerance; and the contributions of adaptive immunity and cross-talk with the innate immune system in driving renal damage. Delineation of basic mechanisms underlying the development of acute and chronic renal damage in lupus nephritis can result in the continued development of more specific and effective treatments. PMID- 25133070 TI - The validity of 2-dimensional measurement of trunk angle during dynamic tasks. AB - PURPOSE/BACKGROUND: Injury screening methods that use three-dimensional (3D) motion analysis accurately predict the risk of injuries, yet are expensive. There is great need for valid, cost-effective techniques that can be used in large scale assessments. Utilizing two-dimensional (2D) measures of lateral trunk motion may identify athletes at risk for lower extremity injury. The purpose of this research was to determine the strength of the relationships between 2D and 3D calculations of lateral trunk angle for female athletes performing a single leg cross drop landing. METHODS: Twenty-one high-school female volleyball players performed a single-leg cross drop landing onto a force plate. The 3D angular trunk motion was calculated, and four different 2D measures of lateral trunk angle were calculated for both left and right landing leg. A one-way multivariate analysis of variance was used to compare 2D measures to the 3D measurements, and Pearson correlations were used to determine the strength of these relationships. RESULTS: The angle formed by the medial shoulder joint center, medial ASIS, and vertical line (LTA4) was similar to the 3D measures of lateral trunk angle during landing (r-values >= 0.62; p-values <= 0.003; mean differences, -1.0 degrees to 1.2 degrees ). CONCLUSIONS: Given the recent focus on the role of the trunk in lower extremity injury, using the 2D LTA4 assessment may expand existing assessments into a composite model that can more accurately assess female athletes at risk for injury than models that do not include trunk analysis. CLINICAL RELEVANCE: Existing models that enable clinicians to effectively identify female athletes at risk for lower extremity injury may be enhanced by including accurate assessments of lateral trunk motion. PMID- 25133071 TI - Comparison of the immediate effect of different types of trunk exercise on the star excursion balance test in male adolescent soccer players. AB - PURPOSE/BACKGROUND: Trunk exercises, such as trunk stabilization exercises (SE) and conventional trunk exercises (CE), are performed to improve static or dynamic balance. Recently, trunk exercises have also been often used as part of warm-up programs. A few studies have demonstrated the immediate effects of SE and CE on static balance. However, immediate effects on dynamic balance are not yet known. Therefore, the purpose of this study was to compare the immediate effect of SE with that of CE on the Star Excursion Balance Test (SEBT). METHODS: Eleven adolescent male soccer players (17.9 +/- 0.3 years, 168.5 +/- 5.4 cm, and 60.1 +/ 5.1 kg) participated in this study. A crossover design was used, and each participant completed three kinds of testing sessions: SE, CE, and non-exercise (NE). Experiments took place for three weeks with three testing sessions, and a 1 week interval was provided between different conditions. Each testing session consisted of three steps: pretest, intervention, and posttest. To assess dynamic balance, the SEBT score in the anterior, posteromedial, and posterolateral directions was measured before and 5 minutes after each intervention program. The data of reach distance were normalized with the leg length to exclude the influence of the leg length on the analysis. RESULTS: The SEBT composite score was significantly improved after the SE (p < 0.05) but did not change after the CE and NE (p > 0.05). Furthermore, in the SE condition, SEBT scores of the posterolateral and posteromedial directions were significantly improved at the posttest, compared with those at the pretest (p < 0.05). CONCLUSIONS: This study demonstrated the immediate improvements in the posteromedial and posterolateral directions of the SEBT only after the SE. This result suggests that the SE used in this study is effective in immediately improving dynamic balance. LEVELS OF EVIDENCE: 3b. PMID- 25133072 TI - Effects of postural control manipulation on visuomotor training performance: comparative data in healthy athletes. AB - PURPOSE/BACKGROUND: Visuomotor ability is an important parameter for neurologic function and effective sport performance. Adding a balance challenge during a structured eye-hand coordination task, such as hitting lights on a light board (DynavisionTM), has not been previously reported. Using Division I football players, the aim of this study was to determine normative data on a dual-task performance regimen combining a visuomotor light board task with a balance task. The intent is to use such normative data and baseline data as part of a concussion management program. METHODS: Division I college football team members, n=105, were consented. Subjects first performed DynavisionTM D2TM Visuomotor Training Device (D2TM) eye-hand coordination tasks, the A* and the RT; they then performed the same tasks with an added balance challenge, standing on a BOSU(r) ball. RESULTS: Ninety-four athletes completed the full testing procedure on the D2TM system. The mean score of the A* test was 93 +/- 11.0 hits per minute; and the mean on the A* test with the added BOSU(r) balance challenge was 83.7 +/- 9.2 hits per minute. The mean RT time was 0.33 +/- 0.036 seconds. Mean reaction time increased to 0.38 +/- 0.063 while the subject stood on the BOSU(r) ball. Performance on the D2TM A* and RT were both statistically significantly different in the dual task condition (p<0.05). CONCLUSIONS: Results show an approximate 10% decline in D2TM performance when healthy individuals stand on a BOSU(r) ball. From the data presented here, the authors determined that there is a 10% decrement in performance when one's balance is challenged on the BOSU(r) ball. A fall in performance of substantially greater than 10% may indicate abnormal vestibulocerebellar regulatory processing of balance and motion. Further research, using these normative data is needed to determine more specific parameters for definitions of impairment and return-to-play and if there is utility for such studies as part of a concussion management program. LEVEL OF EVIDENCE: III. PMID- 25133073 TI - Off-season training habits and preseason functional test measures of division iii collegiate athletes: a descriptive report. AB - PURPOSE/BACKGROUND: Division III (D III) collegiate coaches are challenged to assess athletic readiness and condition their athletes during the preseason. However, there are few reports on off-season training habits and normative data of functional assessment tests among D III athletes. The purpose of this study was to examine off-season training habits of D III athletes and their relationships to the standing long jump (SLJ) and single-leg hop (SLH) tests. METHODS: One-hundred and ninety-three athletes (110 females, age 19.1 +/- 1.1 y; 83 males, age 19.5 +/- 1.3 y) were tested prior to the start of their sports seasons. Athletes reported their off-season training habits (weightlifting, cardiovascular exercise, plyometric exercise, and scrimmage) during the six weeks prior to the preseason. Athletes also performed three maximal effort SLJs and three SLHs. RESULTS: Male athletes reported training more hours per exercise category than their female counterparts. Mean SLJ distances (normalized to height) were 0.79 +/- 0.10 for females and 0.94 +/- 0.12 for males. Mean SLH distances for female athletes' right and left limbs were 0.66 (+/- 0.10) and 0.65 (+/- 0.10), respectively. Mean SLH distances for male athletes' right and left limbs were 0.75 (+/- 0.13) and 0.75 (+/- 0.12), respectively. Several significant differences between off-season training habits and functional test measures were found for both sexes: males [SLJ and weightlifting (p = 0.04); SLH and weightlifting (p = 0.04), plyometrics (p = 0.05)]; females [SLJ and plyometrics (p = 0.04); SLH and scrimmage (p = 0.02)]. CONCLUSION: This study provides normative data for off-season training habits and preseason functional test measures in a D III athlete population. Greater SLJ and SLH measures were associated with increased time during off-season training. CLINICAL RELEVANCE: The findings between functional tests and off-season training activities may be useful for sports medicine professionals and strength coaches when designing their preseason training programs. LEVEL OF EVIDENCE: 4. PMID- 25133074 TI - Reduced hip strength is associated with increased hip motion during running in young adult and adolescent male long-distance runners. AB - STUDY DESIGN: Controlled laboratory study. BACKGROUND AND PURPOSE: Anterior knee pain is one of the most common running symptoms reported in the literature. While the exact etiology is unknown, a lack of hip strength is suggested to contribute to abnormal running mechanics. The purpose of this research study was to evaluate the association between isokinetic hip strength and 3-D running kinematics. METHODS: 33 male high school and collegiate cross country runners participated in this study. Peak isokinetic hip abductor and hip extensor strength were assessed. Each subject also completed a treadmill running protocol at a self-selected speed (mean = 3.8 m/s). 3-D kinematic data were collected at 240 Hz using a 10-camera motion capture system. Pearson correlation coefficients were used to determine the relationship between hip strength and hip range of motion (ROM) during the stance phase of running (p<0.05). RESULTS: Peak isokinetic hip extensor torque was inversely correlated with transverse plane hip ROM (r = -.387, p = .026) but was not significantly related to sagittal plane hip ROM or frontal plane hip ROM. Peak isokinetic hip abductor torque was inversely correlated with frontal plane hip ROM (r=-.462, p=.008) but was not significantly related to either sagittal plane hip ROM or transverse plane hip ROM. Peak isokinetic hip extensor torque and peak isokinetic hip abductor torque were not significantly related to knee kinematics in any plane. CONCLUSIONS: Peak isokinetic hip extensor torque and peak isokinetic hip abductor torque are associated with transverse plane and frontal plane hip kinematics, but not knee kinematics. LEVELS OF EVIDENCE: Level 3b. PMID- 25133075 TI - Patellofemoral pain subjects exhibit decreased passive hip range of motion compared to controls. AB - BACKGROUND: Patellofemoral pain is a common condition without a clear mechanism for its presentation. Recently significant focus has been placed on the hip and its potential role in patellofemoral pain (PFP). The majority of the research has examined hip strength and neuromuscular control. Less attention has been given to hip mobility and its potential role in subjects with PFP. PURPOSE/AIM: The purpose of this study was to compare passive hip range of motion (ROM) of hip extension and hip internal and external rotation in subjects with PFP and healthy control subjects. The hypothesis was that subjects with PFP would present with less total hip ROM and greater asymmetry than controls. DESIGN: Two groups, case controlled. SETTING: Clinical research laboratory. PARTICIPANTS: 30 healthy subjects without pain, radicular symptoms or history of surgery in the low back or lower extremity joints and 30 subjects with a diagnosis of PFP. MAIN OUTCOME MEASURES: Passive hip extension, hip internal rotation (IR) and hip external rotation (ER). A digital inclinometer was used for measurements. RESULTS: There was a statistically significant difference (p<0.001) in hip passive extension between the control group and the PFP group bilaterally. Mean hip extension for the control group was 6.8 degrees bilaterally. For the PFP group, the mean hip extension was -4.0 degrees on the left and -4.3 degrees on the right. This corresponds to a difference of means between groups of 10.8 degrees on the left and 11.1 degrees on the right with a standard error of 2.1 degrees . There was no statistically significant difference (p>0.05) in either hip IR or ER ROM or total rotation between or within groups. CONCLUSIONS: The results of this study indicate that a significant difference in hip extension exists in subjects with PFP compared to controls. These findings suggest that passive hip extension is a variable that should be included within the clinical examination of people with PFP. It may be valuable to consider hip mobility restrictions and their potential impact on assessment of strength and planned intervention in subjects with PFP. LEVEL OF EVIDENCE: 2b. PMID- 25133076 TI - Effect of ankle braces on lower extremity muscle activation during functional exercises in participants with chronic ankle instability. AB - BACKGROUND: Ankle bracing and rehabilitation are common methods to reduce the rate of recurrent ankle sprain in participants with chronic ankle instability (CAI). CAI participants utilize less muscle activity when performing functional exercises compared to healthy controls. The effect of ankle braces on muscle activity during functional exercises in participants with CAI has not been previously studied. PURPOSE: To determine the effect of bracing on motor output as demonstrated by surface EMG amplitudes in participants with CAI during single limb, eyes closed balance, star excursion balance, forward lunge, and lateral hop exercises. METHODS: A descriptive laboratory study was performed. Fifteen young adults with CAI performed functional exercises with and without ankle braces while surface EMG signals were recorded from the tibialis anterior, peroneus longus, lateral gastrocnemius, rectus femoris, biceps femoris, and gluteus medius. The main outcome measures were normalized surface EMG amplitudes (root mean square area) for each muscle, muscles of the shank (distal three muscles), muscles of the thigh (proximal three muscles), and total muscle activity (all six muscles) of the lower extremity. A paired t-test was performed for each dependent variable to compare conditions. The level of significance was set a priori at p <= 0.05 for all analyses. RESULTS: During the forward lunge, bracing significantly reduced muscle activity pre-initial contact in the lateral gastrocnemius and post-initial contact in the peroneus longus. During the star excursion balance anterior reach the peroneus longus, lateral gastrocnemius, rectus femoris, and gluteus medius had significantly less muscle activity during braced trials. Bracing significantly reduced thigh and total muscle activity during the anterior reach and gluteus medius activity during the posterolateral reach. There were no differences between braced and unbraced conditions during the single limb eyes closed balance, star excursion balance posteromedial reach, or during lateral hop exercises. CONCLUSIONS: Clinicians should be aware of the decreased muscle activity that occurs during common rehabilitation exercises when patients with CAI complete those activities while wearing ankle braces. LEVEL OF EVIDENCE: Level III. PMID- 25133077 TI - The effects of conventional physical therapy and eccentric strengthening for insertional achilles tendinopathy. AB - STUDY DESIGN: Single-blind, randomized, clinical trial. BACKGROUND: The effect of eccentric training for mid-portion Achilles tendinopathy is well documented; however, its effect on insertional Achilles tendinopathy is inconclusive. The primary purpose of this study was to investigate the effect of eccentric training on pain and function for individuals with insertional Achilles tendinopathy. METHODS: All patients received a 12-week conventional strengthening protocol. Patients who were randomly assigned to the experimental group received additional eccentric exercises. Patients completed the Short Form-36 Health and Bodily Pain Surveys, the Foot and Ankle Outcomes Questionnaire, and the Visual Analog Scale at initial evaluation, after 6 weeks of therapy, and at 12 weeks after therapy. RESULTS: Thirty-six patients (20 control and 16 experimental; average age 54 years; 72% women) completed the study. Both groups experienced statistically significant decreases in pain and improvements in function. No statistically significant differences were noted between the groups for any of the outcome measures. CONCLUSION: Conventional physical therapy consisting of gastrocnemius, soleus and hamstring stretches, ice massage on the Achilles tendon, and use of heel lifts and night splints with or without eccentric training is effective for treating insertional Achilles tendinopathy. LEVEL OF EVIDENCE: Level 2. PMID- 25133078 TI - A comparison of range of motion change across four posterior shoulder tightness measurements after external rotator fatigue. AB - BACKGROUND: Several glenohumeral joint (GHJ) positions have been recommended for assessing and correcting posterior shoulder tightness (PST) however, there is no agreement on which position is better for differentiating posterior muscle tightness from posterior capsular tightness. The purpose of this study was to compare the range of motion change before and after an external humeral rotator muscle fatigue protocol in order to identify a position that shows maximum range of motion change. METHODS: ROM changes across four PST measurements were compared before, immediately after, at 24 hours after, and 48 hours after an external rotator fatigue protocol. Muscle stiffness of the infraspinatus and the teres minor (using a myotonometer) and external rotation force production (using hand held dynamometry) were measured to verify muscle fatigue. RESULTS: There was a statistically significant interaction between measurement and condition (F = 2.47, p = 0.02). The planned one factor repeated measure ANOVA for each condition revealed that ROM change was statistically significant between PST measurements for all conditions. Post hoc comparisons indicated statistically significant greater overall ROM changes in a measurement combining GHJ extension and internal rotation compared to other tested measurements. There was also a main effect of time on infraspinatus muscle stiffness (F = 10.5, p < 0.0001). Post hoc comparison indicated a statistically significant increase in infraspinatus stiffness immediately after the fatigue protocol (p < 0.05). CONCLUSION: Immediate ROM reduction was observed across all the measurements except horizontal adduction (HAD). Maximum ROM reduction after an external rotation fatigue protocol was measured in a position of GHJ extension. CLINICAL RELEVANCE: Posterior muscle tightness may influence the internal rotation range of motion to a greater extent when measured in glenohumeral joint extension. LEVELS OF EVIDENCE: II-B. PMID- 25133079 TI - A total motion release warm-up improves dominant arm shoulder internal and external rotation in baseball players. AB - CONTEXT: Current literature indicates a correlation between decreased total shoulder range of motion (ROM) and internal rotation (IR) of the dominant arm and increased injury risk in throwers. The optimal method for increasing shoulder ROM, improving performance, and preventing injury is unknown. It is also unknown if treating the non-dominant arm may affect ROM on the dominant side. PURPOSE: To explore the effect of the Total Motion Release (TMR(r)) Trunk Twist (TT) and Arm Raise (AR) on IR and external rotation (ER) of the dominant shoulder in baseball players compared to a traditional dynamic warm-up. DESIGN: Cohort study. SETTING: University athletic training clinic and baseball field. PARTICIPANTS: Pitchers (males, n = 10; age, 18.6 +/- 1.3) recruited from local baseball teams were randomly assigned two one of two groups: TMR(r) treatment group (TMRG; n = 5) or traditional warm-up group (TWG; n = 5). INTERVENTIONS: Baseline IR and ER goniometry range of motion (ROM) measurements were recorded. The TMRG then completed the TMR(r) exercises and post-intervention measurements. The TWG completed a traditional static and dynamic warm-up (e.g., lunges, power skips, sprints, sleeper stretch) and then completed post-intervention measurements. Following the completion of those measurements, the TWG completed the TMR(r) Trunk Twist and Arm Raise protocol and had post-intervention measurements recorded once more. MAIN OUTCOME MEASURES: ROM measures for IR and ER of the dominant shoulder. Alpha level was set at p <= 0.05. RESULTS: Significant differences were present for IR (p = 0.025) and ER (p = 0.014) between the TMRG and the TWG after initial intervention. Significant differences for IR were present in the TWG between baseline and TMR(r) intervention and traditional warm up and TMR(r) intervention. For the TWG, changes in ER were not statistically significant at baseline, post-warm-up, or post- TMR(r) intervention. Significant differences were not present for IR (p = 0.44) or ER (p = 0.23) between groups once TMR(r) had been completed by both groups. CONCLUSIONS: TMR(r) produced larger increases in IR and ER of the throwing shoulder when compared to the TWG. Generalizability is limited, however, by the low number of participants in each group and a potential ceiling effect of attainable ROM gains. Future studies should examine if using a full TMR(r) treatment process is more beneficial. Additionally, future research should compare TMR(r) intervention to other warm-up activities or stretching protocols (e.g. resistance tubing, weighted balls) and examine its effect across other variables (e.g., injury rates, throwing velocity). LEVEL OF EVIDENCE: Clinical Evidence Based Level 2b. PMID- 25133080 TI - Bilateral differences in the upper quarter function of high school aged baseball and softball players. AB - PURPOSE/BACKGROUND: The Upper Quarter Y Balance Test (YBT-UQ) was developed as a way to identify upper extremity and trunk mobility in the open kinetic chain in the reaching limb as well as midrange limitations and asymmetries of upper extremity and core stability in the closed kinetic chain on the stabilizing limb. Performance on the YBT-UQ is similar between genders and between limbs; however, this has not been examined in athletes who participate in sports that result in upper extremity asymmetries. The primary purpose of this study is to determine if differences exist between the throwing vs. non-throwing sides in high-school baseball and softball athletes on the YBT-UQ. METHODS: In order to complete this forty-eight male high school baseball players and seventeen female high school softball players were tested on the YBT-UQ. Reach distances were normalized to arm length (% AL). Comparisons were made between the throwing (T) and non throwing (NT) arm for each direction as well as the composite score. RESULTS: No significant differences were observed between the T and NT arm for the medial (NT: 98.4 +/- 8.6 %AL, T: 99.1 +/- 8.6 %AL, p=0.42), inferolateral (NT: 90.8 +/- 11.8 %AL, T: 90.3 +/- 11.5 %AL, p =0.61), superolateral (NT: 70.6 +/- 10.9 %AL, T: 70.4 +/- 11.1 % AL, p=0.91) reaches, or the composite score (NT: 87.2 +/- 8.9 % AL, T: 86.6 +/- 8.1 %AL, p=0.72). Similarly, no differences were observed between the male baseball and female softball players (p=0.30-0.90). CONCLUSIONS: Based on these findings, it was concluded that there was no difference in performance on the YBT-UQ between throwing and non-throwing limbs in high school baseball and softball players. LEVEL OF EVIDENCE: 3. PMID- 25133082 TI - A modified mobilization-with-movement to treat a lateral ankle sprain. AB - INTRODUCTION AND BACKGROUND: Lateral ankle sprains (LAS) are common in sports medicine and can result in a high rate of re-injury and chronic ankle instability (CAI). Recent evidence supports the use on mobilizations directed at the ankle in patients who have suffered a LAS. The Mulligan Concept of Mobilization-with Movement (MWM) provides an intervention strategy for LASs, but requires pain-free mobilization application and little literature exists on modifications of these techniques. PURPOSE: To present the use of a modified MWM to treat LASs when the traditional MWM technique could not be performed due to patient reported pain and to assess outcomes of the treatment. CASE DESCRIPTION: The subject of this case report is a 23 year-old female collegiate basketball player who had failed to respond to initial conservative treatments after being diagnosed with a lateral ankle sprain. The initial management and subsequent interventions are presented. After re-examination, the addition of a modification of a MWM technique produced immediate and clinically significant changes in patient symptoms. The use of the modified-MWM resulted in full resolution of symptoms and a rapid return to full athletic participation. OUTCOMES: After the initial application of the modified MWM, the patient reported immediate pain-free ankle motion and ambulation. Following a total of 5 treatments, using only the modified MWM and taping technique, the patient was discharged with equal range of motion (ROM) bilaterally, a decreased Disablement in the Physically Active (DPA) Scale score, and an asymptomatic physical exam. Follow-up exam 6 weeks later indicated a full maintenance of these results. DISCUSSION: Recent evidence has been presented to support the use of mobilization techniques to treat patient limitations following ankle injury; however, the majority of evidence is associated with addressing the talar and dorsiflexion limitations. Currently, little evidence is available regarding the use of the MWM technique designed for LASs and the expected outcomes. This case adds to the emerging evidence supporting the use for MWMs to treat ankle pathology and introduces a modification that may be applied in cases where patient reported pain prevents traditional application. LEVEL OF EVIDENCE: Level 5; Single case report. PMID- 25133081 TI - Diagnosis and management of acute medial tibial stress syndrome in a 15 year old female surf life-saving competitor. AB - BACKGROUND AND PURPOSE: As the profound health and cost benefits of physical activity to society are established and participation guidelines implemented, health practitioners are increasingly expected to utilize efficacious and justified injury management and prevention strategies. The complex and multifactorial nature of sports injury makes elucidation of multiple risk factors and how they may subtly and variably interact, difficult. The purpose of this case report is to discuss the differential diagnosis, acute management and rehabilitation of a case of medial tibial stress syndrome (MTSS) in a surf life saving athlete, in the context of sports injury prevention. CASE DESCRIPTION: The subject of this case study, a 15 year old female surf life-saving competitor, presented to the physiotherapist (PT) with recent onset, first episode, bilateral, diffuse posteromedial shin pain. Differential diagnosis, acute management, rehabilitation and preventative strategies for the subject are presented. DISCUSSION: Emerging injury surveillance research in surf life-saving suggests minor and major trauma as primary causative factors, however, the significance of high training volumes is likely underestimated. The influence of biomechanical, and subtle arthrokinematic dysfunctions on established risk factors for MTSS injury and prevention of re-injury for this subject, are also discussed. Furthermore, the concept of preventing tibial stress fracture (TSF) by successfully managing acute MTSS, is presented. Lastly, a critical analysis of reliability of clinical assessment methodologies utilised with the subject is provided. LEVEL OF EVIDENCE: Level 5; Single case report. PMID- 25133083 TI - Functional movement screening: the use of fundamental movements as an assessment of function-part 2. AB - Part 1 of this two-part series (presented in the June issue of IJSPT) provided an introduction to functional movement screening, as well as the history, background, and a summary of the evidence regarding the reliability of the Functional Movement Screen (FMSTM). Part 1 presented three of the seven fundamental movement patterns that comprise the FMSTM, and the specific ordinal grading system from 0-3, used in the their scoring. Specifics for scoring each test are presented. Part 2 of this series provides a review of the concepts associated with the analysis of fundamental movement as a screening system for functional movement competency. In addition, the four remaining movements of the FMSTM, which complement those described in Part 1, will be presented (to complete the total of seven fundamental movements): Shoulder Mobility, the Active Straight Leg Raise, the Trunk Stability Push-up, and Rotary Stability. The final four patterns are described in detail, and the specifics for scoring each test are presented, as well as the proposed clinical implications for receiving a grade less than a perfect "3". The intent of this two part series is to present the concepts associated with screening of fundamental movements, whether it is the FMSTM system or a different system devised by another clinician. Such a fundamental screen of the movement system should be incorporated into pre participation screening and return to sport testing in order to determine whether an athlete has the essential movements needed to participate in sports activities at a level of minimum competency. Part 2 concludes with a discussion of the evidence related to functional movement screening, myths related to the FMSTM, the future of functional movement screening, and the concept of movement as a system. LEVEL OF EVIDENCE: 5. PMID- 25133084 TI - PERMANENT MIGRANTS TO CITIES IN CHINA: HUKOU ORIGIN AND EARNINGS AMONG MEN IN AN ERA OF ECONOMIC TRANSFORMATION. AB - The massive volume of internal migration in China since the late 1970s has attracted considerable research attention. However, the integration of permanent migrants in cities during a time of economic transformation is understudied. Using information on earnings from the 2003 General Social Survey of China, this research examines whether permanent migrants are economically advantaged or disadvantaged in comparison to non-migrants in cities. We find that permanent migrants in cities tend to be economically advantaged and that their advantage depends more on human capital than on political capital. Nevertheless, this does not mean that political capital can be ignored. A nuanced view requires attention to how political and human capital jointly affect earnings in specific economic sectors. PMID- 25133085 TI - Impairment and Functional Interventions for Aphasia: Having it All. AB - Aphasia, a cognitive-linguistic disorder secondary to stroke, is a frequent and often chronic consequence of stroke with detrimental effects on autonomy and health-related quality of life. Treatment of aphasia can be approached in a number of ways. Impairment-based approaches that focus on training a specific linguistic form can be implemented. Additionally, functionally oriented intervention such as supported conversation and aphasia groups are also frequently utilized when providing a treatment program for an individual with aphasia. Creating a treatment approach that includes both impairment and functional methodologies and considers how these relate to the three domains proposed by the International Classification of Functioning Disability and Health (ICF)-body functions and structure, activity, and participation-can provide an individual with aphasia an optimal treatment program that is person-centered and multi-faceted. PMID- 25133086 TI - Adaboost face detector based on Joint Integral Histogram and Genetic Algorithms for feature extraction process. AB - Recently, many classes of objects can be efficiently detected by the way of machine learning techniques. In practice, boosting techniques are among the most widely used machine learning for various reasons. This is mainly due to low false positive rate of the cascade structure offering the possibility to be trained by different classes of object. However, it is especially used for face detection since it is the most popular sub-problem within object detection. The challenges of Adaboost based face detector include the selection of the most relevant features from a large feature set which are considered as weak classifiers. In many scenarios, however, selection of features based on lowering classification errors leads to computation complexity and excess of memory use. In this work, we propose a new method to train an effective detector by discarding redundant weak classifiers while achieving the pre-determined learning objective. To achieve this, on the one hand, we modify AdaBoost training so that the feature selection process is not based any more on the weak learner's training error. This is by incorporating the Genetic Algorithm (GA) on the training process. On the other hand, we make use of the Joint Integral Histogram in order to extract more powerful features. Experimental performance on human faces show that our proposed method requires smaller number of weak classifiers than the conventional learning algorithm, resulting in higher learning and faster classification rates. So, our method outperforms significantly state-of-the-art cascade methods in terms of detection rate and false positive rate and especially in reducing the number of weak classifiers per stage. PMID- 25133087 TI - Investigation of strained deformed state of variable stiffness rod. AB - An equation for bending of a weighable rod with variable transversal stiffness was proposed. On the basis of this analyses the conclusions were drawn about the influence of parameters of construction on values of maximum sag and maximum bending moment. The recommendations for the usage of the simplified model were done. The example of the construction with given parameters for calculation of stiffness and strength according to the represented mathematical models was considered. PMID- 25133089 TI - A characterization of Chover-type law of iterated logarithm. AB - ABSTRACT: Let 0 < alpha <= 2 and - infinity = 1} be a sequence of independent copies of a real-valued random variable X and set S n = X 1+?+X n , n >= 1. We say X satisfies the (alpha,beta)-Chover-type law of the iterated logarithm (and write X?C T L I L(alpha,beta)) if [Formula: see text] almost surely. This paper is devoted to a characterization of X ?C T L I L(alpha,beta). We obtain sets of necessary and sufficient conditions for X?C T L I L(alpha,beta) for the five cases: alpha = 2 and 0 < beta 250 cm/s) were observed during computed flow dynamics analysis in 18.5% of cases. Overall, an additional procedure to ensure patency was required in 19 bypasses intraoperatively and three during follow-up. The presence of aortic dissection had no significant impact on debranching graft-related complications. During multivariate analysis, retropancreatic routing to CT was the only independent predictor of graft-related complications (P=0.006). CONCLUSIONS: Specific visceral graft-related complications were not uncommon in our series and were often associated with clinical consequences. Hemodynamic alterations of debranching grafts were observed in particular at the level of the anastomosis with the superior mesenteric artery. Careful follow-up is mandatory in order to monitor visceral bypasses and facilitate patency when required. PMID- 25133103 TI - Frozen elephant trunk surgery in type B aortic dissection. PMID- 25133104 TI - Role of entry tear size in type B aortic dissection. PMID- 25133105 TI - Best surgical option for arch extension of type B aortic dissection: the open approach. AB - Arch extension of aortic dissection (AD) is reported to occur in 4-25% of patients presenting with acute type B AD. The DeBakey and Stanford classifications do not specifically account for this subset, however, recent studies have demonstrated that the prognosis of patients with arch extension in acute type B AD is virtually identical to that of others with type B AD. In this sense, it seems reasonable to extend the general management principles that are applied to classic acute type B AD even to patients with arch extension. This may be because even in patients with arch extension, most complications occur at locations distal to the arch, and therefore treatment of these patients is similar to that of complicated type B AD, namely thoracic endovascular aortic repair (TEVAR). Conversely, 10% of patients with acute type B AD and arch extension develop complications that are directly related to the arch pathology. This clinical scenario generally necessitates surgical arch repair through a sternotomy approach. The frozen elephant trunk technique combined with arch repair is a very reasonable option to treat this unique clinical entity that involves relatively distal locations of the aortic diseases. Combined arch and descending aorta replacement through thoracotomy is an alternative option particularly when the anatomical features of the target lesions are not suitable for a sternotomy approach or TEVAR. Nonetheless, the reported mortality associated with this approach has been exceedingly high. Hybrid arch repair is another consideration in treating these patients to reduce the treatment-related mortality and morbidity, especially when the arch pathology is limited to the distal part. Nevertheless, the safety and efficacy of this procedure in cases with more extensive arch involvement needs to be assessed in further studies in comparison with other treatment modalities. PMID- 25133106 TI - Medical management in type B aortic dissection. AB - Medical management is generally the preferred treatment for uncomplicated type B acute aortic dissection cases. It is often centered on the use of antihypertensive agents, which alleviates hemodynamic stress on the damaged aortic wall. Methods of medical management and drug selection are still based mainly on personal experience, expert opinion and historical observational studies as randomized controlled studies are lacking. Guidelines from European (ESC), American (ACC/AHA) and Asian (Japan) societies in the last decade have made recommendations on use of medications, but also reaffirmed the lack of evidence for therapeutic approaches and targeted medical management. More recent evidence suggests that there may be type-selective benefits for antihypertensive medications. Here, we will discuss the present understanding of medical management of acute aortic dissection. PMID- 25133107 TI - Open fenestration for complicated acute aortic B dissection. AB - Acute type B aortic dissection (ABAD) is a serious cardiovascular emergency in which morbidity and mortality are often related to the presence of complications at clinical presentation. Visceral, renal, and limb ischemia occur in up to 30% of patients with ABAD and are associated with higher in-hospital mortality. The aim of the open fenestration is to resolve the malperfusion by creating a single aortic lumen at the suprarenal or infrarenal level. This surgical procedure is less invasive than total aortic replacement, thus not requiring extracorporeal support and allowing preservation of the intercostal arteries, which results in decreased risk of paraplegia. Surgical aortic fenestration represents an effective and durable option for treating ischemic complications of ABAD, particularly for patients with no aortic dilatation. In the current endovascular era, this open technique serves as an alternative option in case of contraindications or failure of endovascular management of complicated ABAD. PMID- 25133108 TI - TEVAR for complicated acute type B dissection with malperfusion. PMID- 25133109 TI - Central cannulation (aortic and pulmonary artery) and sequential clamping from distal to proximal in the surgical management of chronic type B dissection utilizing hypothermic circulatory arrest. PMID- 25133110 TI - Pitfalls in the hybrid approach of type B aortic dissection with arch involvement. PMID- 25133112 TI - Marfan syndrome. PMID- 25133113 TI - Highlights from the 50th seminar of the korean society of gastrointestinal endoscopy. AB - The July issue of Clinical Endoscopy deals with selected articles covering the state-of-the-art lectures delivered during the 50th seminar of the Korean Society of Gastrointestinal Endoscopy (KSGE) on March 30, 2014, highlighting educational contents pertaining to either diagnostic or therapeutic gastrointestinal (GI) endoscopy, which contain fundamental and essential points in GI endoscopy. KSGE is very proud of its seminar, which has been presented twice a year for the last 25 years, and hosted more than 3,500 participants at the current meeting. KSGE seminar is positioned as one of premier state-of-the-art seminars for endoscopy, covering topics for novice endoscopists and advanced experts, as well as diagnostic and therapeutic endoscopy. The 50th KSGE seminar consists of more than 20 sessions, including a single special lecture, concurrent sessions for GI endoscopy nurses, and sessions exploring new technologies. Nine articles were selected from these prestigious lectures, and invited for publication in this special issue. This introductory review, prepared by the editors of Clinical Endoscopy, highlights core contents divided into four sessions: upper GI tract, lower GI tract, pancreatobiliary system, and other specialized topic sessions, including live demonstrations and hands-on courses. PMID- 25133114 TI - Plastic and biodegradable stents for complex and refractory benign esophageal strictures. AB - Endoscopic stent placement is a well-accepted and effective alternative treatment modality for complex and refractory esophageal strictures. Among the currently available types of stents, the partially covered self-expanding metal stent (SEMS) has a firm anchoring effect, preventing stent migration and ensuring effective covering of a narrowed segment. However, hyperplastic tissue reaction driven by the uncovered mesh may prevent easy and safe stent removal. As an alternative, a fully covered SEMS decreases the recurrence of dysphagia caused by hyperplastic tissue ingrowth; however, it has a high migration rate. Likewise, although a self-expanding plastic stent (SEPS) reduces reactive hyperplasia, the long-term outcome is disappointing because of the high rate of stent migration. A biodegradable stent has the main benefit of not requiring stent removal in comparison with SEMS and SEPS. However, it still has a somewhat high rate of hyperplastic reaction, and the long-term outcome does not satisfy expectations. Up to now, the question of which type of stent should be recommended for the effective treatment of complex and refractory benign strictures has no clear answer. Therefore, the selection of stent type for endoscopic treatment should be individualized, taking into consideration the endoscopist's experience as well as patient and stricture characteristics. PMID- 25133115 TI - Evaluation and management of caustic injuries from ingestion of Acid or alkaline substances. AB - Although the numbers have decreased compared with in the past, cases of patients who ingest caustic substances and visit the emergency room are not rare. However, well-summarized data about caustic injuries are insufficient. Therefore, in this article, I will discuss the etiologic causative agents, injury mechanism, and clinical characteristics, as well as the endoscopic evaluation of the degree of injury and proper management of the patient, in gastrointestinal caustic injury. PMID- 25133116 TI - Management of acute variceal bleeding. AB - Acute variceal bleeding could be a fatal complication in patients with liver cirrhosis. In patients with decompensated liver cirrhosis accompanied by ascites or hepatic encephalopathy, acute variceal bleeding is associated with a high mortality rate. Therefore, timely endoscopic hemostasis and prevention of relapse of bleeding are most important. The treatment goals for acute variceal bleeding are to correct hypovolemia; achieve rapid hemostasis; and prevent early rebleeding, complications related to bleeding, and deterioration of liver function. If variceal bleeding is suspected, treatment with vasopressors and antibiotics should be initiated immediately on arrival to the hospital. Furthermore, to obtain hemodynamic stability, the hemoglobin level should be maintained at >8 g/dL, systolic blood pressure >90 to 100 mm Hg, heart rate <100/min, and the central venous pressure from 1 to 5 mm Hg. When the patient becomes hemodynamically stable, hemostasis should be achieved by performing endoscopy as soon as possible. For esophageal variceal bleeding, endoscopic variceal ligation is usually performed, and for gastric variceal bleeding, endoscopic variceal obturation is performed primarily. If it is considered difficult to achieve hemostasis through endoscopy, salvage therapy may be carried out while keeping the patient hemodynamically stable. PMID- 25133117 TI - Endoscopy for nonvariceal upper gastrointestinal bleeding. AB - Endoscopy for acute nonvariceal upper gastrointestinal bleeding plays an important role in primary diagnosis and management, particularly with respect to identification of high-risk stigmata lesions and to providing endoscopic hemostasis to reduce the risk of rebleeding and mortality. Early endoscopy, defined as endoscopy within the first 24 hours after presentation, improves patient outcome and reduces the length of hospitalization when compared with delayed endoscopy. Various endoscopic hemostatic methods are available, including injection therapy, mechanical therapy, and thermal coagulation. Either single treatment with mechanical or thermal therapy or a treatment that combines more than one type of therapy are effective and safe for peptic ulcer bleeding. Newly developed methods, such as Hemospray powder and over-the-scope clips, may provide additional options. Appropriate decisions and specific treatment are needed depending upon the conditions. PMID- 25133118 TI - Management of Antithrombotic Therapy for Gastroenterological Endoscopy from a Cardio-Cerebrovascular Physician's Point of View. AB - Periprocedural management of antithrombotics for gastroenterological endoscopy is a common clinical issue. To decide how to manage the use of antithrombotics in patients undergoing endoscopy, the risk for hemorrhage and thromboembolism during the procedure must be considered. For low-risk procedures, no adjustments in antithrombotics are needed. For high-risk procedures with a low thromboembolic risk, discontinuation of warfarin at 5 days, and clopidogrel at 5 to 7 days before the procedure has been recommended. However, it is better to continue aspirin use even during high-risk procedures. A heparin bridging therapy may be considered before endoscopy in patients with a high thromboembolic risk. The management of patients taking antithrombotics remains complex, especially in high risk settings. PMID- 25133119 TI - Prerequisites of colonoscopy. AB - Colonoscopy is a widely accepted method for the evaluation of the colon and terminal ileum. Its diagnostic accuracy and therapeutic safety are influenced by prerequisites, including modulation of medication and bowel cleansing. Appropriate choices of sedative medication and bowel-cleansing regimen, together with diet modification, should be made based on the patient's underlying disease, age, and medication intake. Moreover, effective methods for patient education regarding bowel preparation should be considered. PMID- 25133120 TI - Equipment-based image-enhanced endoscopy for differentiating colorectal polyps. AB - The use of colonoscopy for the screening and surveillance of colorectal cancer has increased. However, the miss rate of advanced colorectal neoplasm is known to be 2% to 6%, which could be affected by the image intensity of colorectal lesions. Image-enhanced endoscopy (IEE) is capable of highlighting lesions, which can improve the colorectal adenoma detection rate and diagnostic accuracy. Equipment-based IEE methods, such as narrow band imaging (NBI), Fujinon intelligent color enhancement (FICE), and i-Scan, are used to observe the mucosal epithelium of the microstructure and capillaries of the lesion, and are helpful in the detection and differential diagnosis of colorectal tumors. Although NBI is similar to chromoendoscopy in terms of adenoma detection rates, NBI can be used to differentiate colorectal polyps and to predict the submucosal invasion of malignant tumors. It is also known that FICE and i-Scan are similar to NBI in their detection rates of colorectal lesions. Through more effective and advanced endoscopic equipment, diagnostic accuracy could be improved and new treatment paradigms developed. PMID- 25133121 TI - Preparation of high-risk patients and the choice of guidewire for a successful endoscopic retrograde cholangiopancreatography procedure. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is an essential technique for the diagnosis and treatment of pancreatobiliary diseases. However, ERCP related complications such as pancreatitis, cholangitis, hemorrhage, and perforation may be problematic. For a successful and safe ERCP, preprocedural evaluations of the patients and intervention-related risk factors are needed. Furthermore, in light of the recent population aging and increase in chronic cardiopulmonary diseases in Korea, precautions including endoscopic sedation and prevention of cardiopulmonary complications should be considered. In this literature review, we describe these risk factors and the use of endoscopic sedation. In addition, we reviewed the commonly available guidewires, including their materials and options, used as a basic accessory for ERCP procedures. PMID- 25133122 TI - The management of endoscopic retrograde cholangiopancreatography-related duodenal perforation. AB - Uneventful duodenal perforation during endoscopic retrograde cholangiopancreatography (ERCP) is an uncommon but occasionally fatal complication. ERCP-related perforations may occur during sphincterotomy and improper manipulation of the equipment and scope. Traditionally, duodenal perforation has been treated with early surgical repair. Recently, nonoperative early endoscopic management techniques including clips or fibrin glue have been reported. In the present paper we review the literature pertaining to the treatment of perforations. PMID- 25133123 TI - A case report of primary duodenal tuberculosis mimicking a malignant tumor. AB - Tuberculosis remains a serious infectious disease with primary features of pulmonary manifestation in Korea. However, duodenal tuberculosis is rare in gastrointestinal cases of extrapulmonary tuberculosis. Here, we report a case of primary duodenal tuberculosis mistaken as a malignant tumor and diagnosed with QuantiFERON-TB GOLD (Cellestis Ltd.) in an immunocompetent male patient. PMID- 25133124 TI - Primary papillary thyroid carcinoma diagnosed by using endoscopic ultrasound with fine needle aspiration. AB - There is paucity in the literature on the use of endoscopic ultrasound (EUS) for evaluating the thyroid gland. We report the first case of primary papillary thyroid cancer diagnosed by using EUS and fine needle aspiration (FNA). A 66-year old man underwent EUS for the evaluation of mediastinal lymphadenopathy. FNA of the lymph nodes showed benign findings. A hypoechoic mass was noted in the right lobe of the thyroid gland. Therefore, FNA was performed. The cytological results were consistent with primary papillary thyroid cancer. PMID- 25133125 TI - A case of endoscopic full-thickness resection in a patient with gastric high grade dysplasia unsuitable for endoscopic submucosal dissection. AB - Gastric high-grade dysplasia is an important premalignant lesion in gastric epithelial cells and has a high possibility of transforming to adenocarcinoma. Therefore, biopsy-proven high-grade dysplasia should be treated with en bloc resection methods such as endoscopic mucosal resection or endoscopic submucosal dissection (ESD). We report the case of a 63-year-old male patient, diagnosed with gastric high-grade dysplasia at the angle and lesser curvature side of the lower body. The patient was initially treated with ESD, although histopathology subsequently showed horizontal margin involvement. Since the lesion was diffusely edematous and margins were uncertain because of the previous ESD treatment, we chose to treat the patient with laparoscopy-assisted endoscopic full-thickness resection (EFTR). EFTR is a recently developed procedure, which uses both endoscopic and laparoscopic techniques to resect the full-thickness of the tissue. The final pathologic report revealed high-grade dysplasia and a focal intramucosal carcinoma of 0.8*0.7 cm. We conclude that EFTR can be an effective alternative treatment in gastric high-grade dysplasia unsuitable for ESD. PMID- 25133126 TI - Xanthoma of the esophagus. AB - Xanthoma is an uncommon nonneoplastic lesion resulting from the accumulation of histiocytes. It predominantly shows cutaneous manifestations associated with dyslipidemia. However, xanthoma of the esophagus is extremely rare. To the best of our knowledge, only 14 cases have been reported thus far. The clinical significance of this lesion has not been established. However, this lesion should be distinguished grossly from ectopic sebaceous glands and small subepithelial tumors such as carcinoid and granular cell tumor. Moreover, signet ring cell carcinoma, which contains round cells with abundant cytoplasm and has similar histologic features to xanthoma, should be distinguished microscopically. PMID- 25133127 TI - Endoscopic Management of Rectal Dieulafoy's Lesion: A Case Series and Optimal Treatment. AB - Rectal Dieulafoy's lesion (DL) is rare cause of lower gastrointestinal bleeding. Because of its rarity, there is no consensus on the optimal endoscopic hemostasis technique for rectal DL. We analyzed six patients who underwent endoscopic management for rectal DL after presenting with hematochezia at a single institute over 10 years. Of the six patients, three underwent endoscopic band ligation (EBL) and three underwent endoscopic hemoclip placement (EHP). Only one patient was treated with thermocoagulation. There were no immediate complications in any of the patients. None of the patients required a procedure or surgery for the treatment of rebleeding. Mean procedure times of EBL and EHP were 5.25 minutes and 7 minutes, respectively. Both EHP and EBL are shown to be effective in the treatment of bleeding rectal DL. We suggest that EBL may have potential as the preferred therapy owing to its superiority in technical and economic aspects, especially in elderly and high-risk patients. PMID- 25133129 TI - Reader's Forum. PMID- 25133128 TI - Electrohydraulic lithotripsy of an impacted enterolith causing acute afferent loop syndrome. AB - Afferent loop syndrome caused by an impacted enterolith is very rare, and endoscopic removal of the enterolith may be difficult if a stricture is present or the normal anatomy has been altered. Electrohydraulic lithotripsy is commonly used for endoscopic fragmentation of biliary and pancreatic duct stones. A 64 year-old man who had undergone subtotal gastrectomy and gastrojejunostomy presented with acute, severe abdominal pain for a duration of 2 hours. Initially, he was diagnosed with acute pancreatitis because of an elevated amylase level and pain, but was finally diagnosed with acute afferent loop syndrome when an impacted enterolith was identified by computed tomography. We successfully removed the enterolith using direct electrohydraulic lithotripsy conducted using a transparent cap-fitted endoscope without complications. We found that this procedure was therapeutically beneficial. PMID- 25133130 TI - Comparison of frictional forces between aesthetic orthodontic coated wires and self-ligation brackets. AB - OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of polymer- and rhodium-coated wires compared to uncoated wires by measuring the frictional forces using self-ligation brackets. METHODS: 0.016-inch nickel titanium (NiTi) wires and 0.017 * 0.025-inch stainless steel (SS) wires were used, and the angulations between the brackets and wires were set to 0 degrees , 5 degrees , and 10 degrees . Upper maxillary premolar brackets (Clippy-C(r)) with a 0.022-inch slot were selected for the study and a tensile test was performed with a crosshead speed of 5 mm/min. The maximum static frictional forces and kinetic frictional forces were recorded and compared. RESULTS: The maximum static frictional forces and the kinetic frictional forces of coated wires were equal to or higher than those of the uncoated wires (p < 0.05). The maximum static frictional forces of rhodium-coated wires were significantly higher than those of polymer-coated wires when the angulations between the brackets and wires were set to (i) 5 degrees in the 0.016-inch NiTi wires and (ii) all angulations in the 0.017 * 0.025-inch SS wires (p < 0.05). The kinetic frictional forces of rhodium coated wires were higher than those of polymer-coated wires, except when the angulations were set to 0 degrees in the 0.016-inch NiTi wires (p < 0.05). CONCLUSIONS: Although the frictional forces of the coated wires with regards to aesthetics were equal to or greater than those of the uncoated wires, a study under similar conditions regarding the oral cavity is needed in order to establish the clinical implications. PMID- 25133131 TI - Randomized controlled clinical trial of oral health-related quality of life in patients wearing conventional and self-ligating brackets. AB - OBJECTIVE: The aim of this randomized controlled clinical trial was to compare oral health-related quality of life (OHRQoL) of patients treated with conventional, active self-ligating (ASL), and passive self-ligating (PSL) brackets in different therapeutic phases. METHODS: Sixty patients (mean age 18.3 years; 29 males and 31 females) requiring orthodontic treatment were randomly and equally assigned to receive conventional (Victory Series), ASL (In-Ovation R), or PSL (Damon 3MX) brackets. OHRQoL was measured with a self-administered modified 16-item Malaysian version of the Oral Health Impact Profile for immediate (soon after the visit) and late (just before the subsequent visit) assessments of the bonding and activation phases. Data were analyzed with the Kruskal-Wallis and chi square tests. RESULTS: The PSL and ASL groups showed more immediate and late impacts in the bonding phase, respectively; the conventional group was affected in both the assessments. The first activation phase had similar impacts in the groups. After the second activation, the conventional group showed more immediate impacts, whereas the PSL and ASL groups had more late impacts. The commonly affected domains were "physical disability," "functional limitation," "physical pain," and "psychological discomfort." No significant differences in the prevalence and severity of immediate and late impacts on OHRQoL of the patients were noted in any therapeutic phase. CONCLUSIONS: No bracket system seems to ensure superior OHRQoL. This information could be useful for explaining the therapeutic phases, especially the initial one, and selecting the optimal bracket system based on the patient's preference. PMID- 25133132 TI - Geometrical design characteristics of orthodontic mini-implants predicting maximum insertion torque. AB - OBJECTIVE: To determine the unique contribution of geometrical design characteristics of orthodontic mini-implants on maximum insertion torque while controlling for the influence of cortical bone thickness. METHODS: Total number of 100 cylindrical orthodontic mini-implants was used. Geometrical design characteristics of ten specimens of ten types of cylindrical self-drilling orthodontic mini-implants (Ortho Easy(r), Aarhus, and Dual TopTM) with diameters ranging from 1.4 to 2.0 mm and lengths of 6 and 8 mm were measured. Maximum insertion torque was recorded during manual insertion of mini-implants into bone samples. Cortical bone thickness was measured. Retrieved data were analyzed in a multiple regression model. RESULTS: Significant predictors for higher maximum insertion torque included larger outer diameter of implant, higher lead angle of thread, and thicker cortical bone, and their unique contribution to maximum insertion torque was 12.3%, 10.7%, and 24.7%, respectively. CONCLUSIONS: The maximum insertion torque values are best controlled by choosing an implant diameter and lead angle according to the assessed thickness of cortical bone. PMID- 25133133 TI - Facial profile parameters and their relative influence on bilabial prominence and the perceptions of facial profile attractiveness: A novel approach. AB - OBJECTIVE: To evaluate the relative importance of bilabial prominence in relation to other facial profile parameters in a normal population. METHODS: Profile stimulus images of 38 individuals (28 female and 10 male; ages 19-25 years) were shown to an unrelated group of first-year students (n = 42; ages 18-24 years). The images were individually viewed on a 17-inch monitor. The observers received standardized instructions before viewing. A six-question questionnaire was completed using a Likert-type scale. The responses were analyzed by ordered logistic regression to identify associations between profile characteristics and observer preferences. The Bayesian Information Criterion was used to select variables that explained observer preferences most accurately. RESULTS: Nasal, bilabial, and chin prominences; the nasofrontal angle; and lip curls had the greatest effect on overall profile attractiveness perceptions. The lip-chin throat angle and upper lip curl had the greatest effect on forehead prominence perceptions. The bilabial prominence, nasolabial angle (particularly the lower component), and mentolabial angle had the greatest effect on nasal prominence perceptions. The bilabial prominence, nasolabial angle, chin prominence, and submental length had the greatest effect on lip prominence perceptions. The bilabial prominence, nasolabial angle, mentolabial angle, and submental length had the greatest effect on chin prominence perceptions. CONCLUSIONS: More prominent lips, within normal limits, may be considered more attractive in the profile view. Profile parameters have a greater influence on their neighboring aesthetic units but indirectly influence related profile parameters, endorsing the importance of achieving an aesthetic balance between relative prominences of all aesthetic units of the facial profile. PMID- 25133134 TI - Modification of surface pretreatment of white spot lesions to improve the safety and efficacy of resin infiltration. AB - OBJECTIVE: A low-viscosity resin (infiltrant) was used to inhibit the progression of white spot lesions (WSLs) and resolve associated esthetic issues. An alternative pretreatment was explored to increase the pore volume of the surface layer of the WSLs. Also, the penetration effects of the infiltrant were evaluated for various pretreatments. METHODS: Sixty two artificial lesions were fabricated on bovine teeth. As a positive control, 15% HCl gel was applied for 120 seconds. Further, 37% H3PO4 gel was applied for 30 seconds using three methods. The samples were divided as follows: H3PO4 only group, H3PO4 sponge group, and H3PO4 brush group. The acid was gently rubbed with the applicators (i.e., a sponge or brush) throughout the application time. To compare the effects of resin infiltration, twenty paired halves of specimens were treated with an infiltrant (ICON(r)). RESULTS: Thicknesses of the removed surface layers and infiltrated areas were evaluated by confocal laser scanning microscope. The positive control and the 37% H3PO4 brush group failed to show significant differences in the removed thickness (p > 0.05); however, the mean percentage of the infiltrated area was higher in the 37% H3PO4 brush group (84.13 +/- 7.58%) than the positive control (63.51 +/- 7.62%, p < 0.001). Scanning electron microscope observations indicate higher pore volumes for the 37% H3PO4 brush group than for the positive control. CONCLUSIONS: Application of 37% H3PO4 with a brush for 30 seconds increased the pore volume of WSL surface layers and the percentage of infiltrated areas in comparison to the use of 15% HCl for 120 seconds. PMID- 25133135 TI - Treatment and retention of relapsed anterior open-bite with low tongue posture and tongue-tie: A 10-year follow-up. AB - The purpose of the current report is to present 6-year long-term stability and 10 year follow-up data for an adult patient who was treated with a tongue elevator for relapsed anterior open-bite. The 19-year-old male patient presented with the chief complaint of difficulty in chewing his food. Collectively, clinical and radiographic examinations revealed an anterior open-bite, low tongue posture, and tongue-tie. The patient opted for orthodontic treatment alone, without any surgical procedure. A lingual frenectomy was recommended to avoid the risk of relapse, but the patient declined because he was not experiencing tongue discomfort. Initial treatment of the anterior open-bite with molar intrusion and tongue exercises was successful, but relapse occurred during the retention period. A tongue elevator was used for retreatment, because the approach was minimally invasive and suited the patient's requirements regarding discomfort, cost, and time. The appliance changed the tongue posture and generated an altered tongue force, which ultimately resulted in intrusive dentoalveolar effects, and a subsequent counterclockwise rotation of the mandible. The results showed long term stability and were maintained for six years through continual use of the tongue elevator. The results of this case indicated that a tongue elevator could be used not only as an alternative treatment for open-bite, but also as an active retainer. PMID- 25133136 TI - Interdisciplinary rehabilitation of a root-fractured maxillary central incisor: A 12-year follow-up case report. AB - Single-tooth implantation has become a common treatment solution for replacement of a root-fractured maxillary incisor in adults, but the long-term esthetic results can be unfavorable due to progressive marginal bone loss, resulting in gingival recession. In this case report, a maxillary central incisor with a root fracture in its apical one-third was orthodontically extruded and extracted in a 21-year-old female. Implant surgery was performed after a 3-month healing period, and the final crown was placed about 12 months after extraction. After 12 years, favorable osseous and gingival architectures were visible with adequate bone height and thickness at the buccal cortical plate, and no gingival recession was seen around the implant-supported crown. Although modern dentistry has been shifting toward simplified, clinical procedures and shorter treatment times, both general dentists and orthodontists should be aware of the possible long-term esthetic advantages of orthodontic extrusion of hopelessly fractured teeth for highly esthetically demanding areas and should educate and motivate patients regarding the choice of this treatment solution, if necessary. PMID- 25133138 TI - Secondhand Smoke Exposure and Severity of Attention-Deficit/Hyperactivity Disorder in Preschoolers: A Pilot Investigation. AB - BACKGROUND: Less is known about the effects of secondhand smoke (SHS) on mental health as compared with other medical disorders. OBJECTIVE: The aims of this study were to examine the following: 1) the association of SHS exposure with childhood attention-deficit/hyperactivity (ADHD) and disruptive disorders; and 2) the association of maternal recall of a child's SHS exposure and that child's exposure as measured by bioassay. METHOD: Sixty children had their saliva collected and assayed for cotinine when they were 4 years old and again when they were 6 years old. Phone interview data were collected to assess maternal recall of the children's exposure to SHS at these ages. The children were assessed annually for ADHD and disruptive disorders. Repeated measures analysis of exposure level by child characteristics was performed. RESULTS: Greater ADHD and conduct disorder severity scores were associated with greater child smoke exposure (ADHD severity, P = .043; conduct disorder severity, P = .035). A large proportion of mothers reported that their children had no exposure to SHS, despite high levels of measured cotinine in the children's saliva. CONCLUSIONS: An association between SHS exposure and ADHD and conduct disorder symptoms was found. Children and parents may benefit from parent education regarding the deleterious effects of SHS. PMID- 25133137 TI - Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells. AB - Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here, we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 10(6) white blood cells (WBCs). Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control WBCs. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples of patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here, we used flow based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients. PMID- 25133139 TI - Current Perspectives on Viable but Non-Culturable (VBNC) Pathogenic Bacteria. AB - Under stress conditions, many species of bacteria enter into starvation mode of metabolism or a physiologically viable but non-culturable (VBNC) state. Several human pathogenic bacteria have been reported to enter into the VBNC state under these conditions. The pathogenic VBNC bacteria cannot be grown using conventional culture media, although they continue to retain their viability and express their virulence. Though there have been debates on the VBNC concept in the past, several molecular studies have shown that not only can the VBNC state be induced under in vitro conditions but also that resuscitation from this state is possible under appropriate conditions. The most notable advance in resuscitating VBNC bacteria is the discovery of resuscitation-promoting factor (Rpf), which is a bacterial cytokines found in both Gram-positive and Gram-negative organisms. VBNC state is a survival strategy adopted by the bacteria, which has important implication in several fields, including environmental monitoring, food technology, and infectious disease management; and hence it is important to investigate the association of bacterial pathogens under VBNC state and the water/foodborne outbreaks. In this review, we describe various aspects of VBNC bacteria, which include their proteomic and genetic profiles under the VBNC state, conditions of resuscitation, methods of detection, antibiotic resistance, and observations on Rpf. PMID- 25133142 TI - Dissociative symptoms and dissociative disorders comorbidity in obsessive compulsive disorder: Symptom screening, diagnostic tools and reflections on treatment. AB - Borderline personality disorder, conversion disorder and obsessive compulsive disorder frequently have dissociative symptoms. The literature has demonstrated that the level of dissociation might be correlated with the severity of obsessive compulsive disorder (OCD) and that those not responding to treatment had high dissociative symptoms. The structured clinical interview for DSM-IV dissociative disorders, dissociation questionnaire, somatoform dissociation questionnaire and dissociative experiences scale can be used for screening dissociative symptoms and detecting dissociative disorders in patients with OCD. However, a history of neglect and abuse during childhood is linked to a risk factor in the pathogenesis of dissociative psychopathology in adults. The childhood trauma questionnaire-53 and childhood trauma questionnaire-40 can be used for this purpose. Clinicians should not fail to notice the hidden dissociative symptoms and childhood traumatic experiences in OCD cases with severe symptoms that are resistant to treatment. Symptom screening and diagnostic tools used for this purpose should be known. Knowing how to treat these pathologies in patients who are diagnosed with OCD can be crucial. PMID- 25133141 TI - Progress in sensorimotor rehabilitative physical therapy programs for stroke patients. AB - Impaired motor and functional activity following stroke often has negative impacts on the patient, the family and society. The available rehabilitation programs for stroke patients are reviewed. Conventional rehabilitation strategies (Bobath, Brunnstrom, proprioception neuromuscular facilitation, motor relearning and function-based principles) are the mainstream tactics in clinical practices. Numerous advanced strategies for sensory-motor functional enhancement, including electrical stimulation, electromyographic biofeedback, constraint-induced movement therapy, robotics-aided systems, virtual reality, intermittent compression, partial body weight supported treadmill training and thermal stimulation, are being developed and incorporated into conventional rehabilitation programs. The concept of combining valuable rehabilitative procedures into "a training package", based on the patient's functional status during different recovery phases after stroke is proposed. Integrated sensorimotor rehabilitation programs with appropriate temporal arrangements might provide great functional benefits for stroke patients. PMID- 25133143 TI - Metabolic syndrome and childhood trauma: Also comorbidity and complication in mood disorder. AB - Studies for prevalence and causal relationship established that addressing comorbidities of mental illnesses with medical disease will be another revolution in psychiatry. Increasing number of evidence shows that there is a bidirectional connection between mood disorders and some medical diseases. Glucocorticoid/insulin signal mechanisms and immunoenflammatory effector systems are junction points that show pathophysiology between bipolar disorder and general medical situations susceptible to stress. A subgroup of mood disorder patients are under risk of developing obesity and diabetes. Their habits and life styles, genetic predisposition and treatment options are parameters that define this subgroup. Medical disease in adults had a significant relationship to adverse life experiences in childhood. This illustrates that adverse experiences in childhood are related to adult disease by two basic etiologic mechanisms: (1) conventional risk factors that actually are compensatory behaviors, attempts at self-help through the use of agents and foods; and (2) the effects of chronic stress. PMID- 25133140 TI - Psychosocial perspectives and the issue of prevention in childhood obesity. AB - A dramatic increase in childhood overweight/obesity has been recognized globally over the past 50 years. This observed increase may reflect genetic, as well as psychological, environmental, and socio-cultural influences. In the first part of this review, we present an updated summary of the psychosocial factors associated with this change and discuss possible ways in which they operate. Among these factors, lower socio economic status (in both industrialized and non industrialized countries), being female, belonging to a minority group, and being exposed to adverse life events may all be associated with a greater risk of childhood overweight/obesity. These influences may be mediated via a variety of mechanisms, in particular above-average food intake of low nutritional quality and reduction in physical activity. Other important psychosocial mediators include the influence of the family and peer environment, and exposure to the media. In the second part of the review, we discuss the potential of psychosocial prevention programs to intervene in the processes involved in the rise of childhood overweight/obesity. Two points are emphasized. First, prevention programs should be multidisciplinary, combining the knowledge of experts from different professions, and taking into consideration the important role of the family environment and relevant influential social organizations, particularly school. Second, effective change is unlikely to occur without large-scale programs carried out on a public policy level. PMID- 25133144 TI - Pseudocyesis, delusional pregnancy, and psychosis: The birth of a delusion. AB - Both pseudocyesis and delusional pregnancy are said to be rare syndromes, but are reported frequently in developing countries. A distinction has been made between the two syndromes, but the line of demarcation is blurred. The aim of this paper is to review recent cases of pseudocyesis/delusional pregnancy in order to learn more about biopsychosocial antecedents. The recent world literature (2000-2014) on this subject (women only) was reviewed, making no distinction between pseudocyesis and delusional pregnancy. Eighty case histories were found, most of them originating in developing countries. Fifty patients had been given a diagnosis of psychosis, although criteria for making the diagnosis were not always clear. The psychological antecedents included ambivalence about pregnancy, relationship issues, and loss. Very frequently, pseudocyesis/delusional pregnancy occurred when a married couple was infertile and living in a pronatalist society. The infertility was attributed to the woman, which resulted in her experiencing substantial distress and discrimination. When antipsychotic medication was used to treat psychotic symptoms in these women, it led to high prolactin levels and apparent manifestations of pregnancy, such as amenorrhea and galactorrhea, thus reinforcing a false conviction of pregnancy. Developing the erroneous belief that one is pregnant is an understandable process, making the delusion of pregnancy a useful template against which to study the evolution of other, less explicable delusions. PMID- 25133145 TI - Tree stand falls: A persistent cause of neurological injury in hunting. AB - AIM: To characterize and compare our current series of patients to prior reports in order to identify any changes in the incidence of neurological injury related to hunting accidents in Rochester, New York. METHODS: All tree stand-related injuries referred to our regional trauma center from September 2003 through November 2011 were reviewed. Information was obtained from the hospital's trauma registry and medical records were retrospectively reviewed for data pertaining to the injuries. RESULTS: Fifty-four patients were identified. Ninety-six percent of patients were male with a mean age of 47.9 years (range 15-69). The mean Injury Severity Score was 12.53 +/- 1.17 (range 2-34). The average height of fall was 18.2 feet (range 4-40 feet). All patients fell to the ground with the exception of one who landed on rocks, and many hit the tree or branches on the way down. A reason for the fall was documented in only 13 patients, and included tree stand construction (3), loss of balance (3), falling asleep (3), structural failure (2), safety harness breakage (3) or light-headedness (1). The most common injuries were spinal fractures (54%), most commonly in the cervical spine (69%), followed by the thoracic (38%) and lumbar (21%) spine. Eight patients required operative repair. Head injuries occurred in 22%. Other systemic injuries include rib/clavicular fractures (47%), pelvic fractures (11%), solid organ injury (23%), and pneumothorax or hemothorax (19%). No patient deaths were reported. The average hospital length of stay was 6.56 +/- 1.07 d. Most patients were discharged home without (72%) or with (11%) services and 17% required rehabilitation. CONCLUSION: Falls from hunting tree stands are still common, with a high rate of neurological injury. Compared to a decade ago we have made no progress in preventing these neurological injuries, despite an increase in safety advances. Neurosurgeons must continue to advocate for increased safety awareness and participate in leadership roles to improve outcomes for hunters. PMID- 25133146 TI - Intracerebroventricular opiate infusion for refractory head and facial pain. AB - AIM: To study the risks and benefits of intracerebroventricular (ICV) opiate pumps for the management of benign head and face pain. METHODS: SSix patients with refractory trigeminal neuralgia and/or cluster headaches were evaluated for implantation of an ICV opiate infusion pump using either ICV injections through an Ommaya reservoir or external ventricular drain. Four patients received morphine ICV pumps and two patientS received a hydromorphone pump. Of the Four patients with morphine ICV pumps, one patient had the medication changed to hydromorphone. Preoperative and post-operative visual analog scores (VAS) were obtained. Patients were evaluated post-operatively for a minimum of 3 mo and the pump dosage was adjusted at each outpatient clinic visit according to the patient's pain level. RESULTS: All 6 patients had an intracerebroventricular opiate injection trial period, using either an Ommaya reservoir or an external ventricular drain. There was an average VAS improvement of 75.8%. During the trial period, no complications were observed. Pump implantation was performed an average of 3.7 wk (range 1-7) after the trial injections. After implantation, an average of 20.7 +/- 8.3 dose adjustments were made over 3-56 mo after surgery to achieve maximal pain relief. At the most recent follow-up (26.2 mo, range 3-56), VAS scores significantly improved from an average of 7.8 +/- 0.5 (range 6-10) to 2.8 +/- 0.7 (range 0-5) at the final dose (mean improvement 5.0 +/- 1.0, P < 0.001). All patients required a stepwise increase in opiate infusion rates to achieve maximal benefit. The most common complications were nausea and drowsiness, both of which resolved with pump adjustments. On average, infusion pumps were replaced every 4-5 years. CONCLUSION: These results suggest that ICV delivery of opiates may potentially be a viable treatment option for patients with intractable pain from trigeminal neuralgia or cluster headache. PMID- 25133147 TI - Distal biceps tendon rupture reconstruction using muscle-splitting double incision approach. AB - AIM: To evaluate the clinical and functional results after repair of distal biceps tendon tears, following the Morrey's modified double-incision approach. METHODS: We retrospectively reviewed 47 patients with distal rupture of biceps brachii treated between 2003 and 2012 in our Orthopedic Department with muscle splitting double-incision technique. Outcome measures included the Mayo elbow performance, the DASH questionnaire, patient's satisfaction, elbow and forearm motion, grip strength and complications occurrence. RESULTS: At an average 18 mo follow-up (range, 7 mo-10 years) the average Mayo elbow performance and DASH score were respectively 97.2 and 4.8. The elbow flexion range was 94%, extension was -2 degrees , supination was 93% and pronation 96% compared with the uninjured limb. The mean grip strength, expressed as percentage of respective contralateral limb, was 83%. The average patient satisfaction rating on a Likert scale (from 0 to 10) was 9.4. The following complications were observed: 3 cases of heterotopic ossification (6.4%), one (2.1%) re-rupture of the tendon at the site of reattachment and 2 cases (4.3%) of posterior interosseous nerve palsy. No complication required further surgical treatment. CONCLUSION: This technique allows an anatomic reattachment of distal biceps tendon at the radial tuberosity providing full functional recovery with low complication rate. PMID- 25133148 TI - Dabigatran etixilate and traumatic brain injury: Evolving anticoagulants require evolving care plans. AB - AIM: To investigate the outcomes of trauma patients with traumatic brain injury (TBI) on Dabigatran Etexilate (DE). METHODS: Following IRB approval, all patients taking DE who were admitted to our level 1 trauma service were enrolled in the study. Injury complexity, length of stay (LOS), intensive care length of stay, operative intervention, therapeutic interventions and outcomes were analyzed retrospectively. RESULTS: Twenty-eight of 4310 admissions were taking DE. Eleven patients were excluded on concurrent antiplatelet therapy. Average age was 77.14 years (64-94 years), and average LOS was 4.7 d (1-35 d). Thirty-two percent were admitted with intracranial hemorrhage. Eighteen percent received factor VII, and 22% received dialysis in attempts to correct coagulopathy. Mortality was 21%. CONCLUSION: The low incidence, absence of reversal agents, and lack of practice guidelines makes managing patients with TBI taking DE frustrating and provider specific. Local practice guidelines may be helpful in managing such patients. PMID- 25133149 TI - Desmoplastic small round cell tumor with atypical immunohistochemical profile and rhabdoid-like differentiation. AB - Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive malignant neoplasm of unknown origin, and is comprised of small round cells with a characteristic desmoplastic stroma. DSRCT typically expresses epithelial, mesenchymal and neural markers simultaneously. We describe a case of DSRCT with an atypical immunohistochemical profile and rhabdoid-like tumor cells on electron microscopy. In the present case, the neoplastic cells were positive only for vimentin, desmin (cytoplasmic membranous pattern) and CD56, and negative for smooth muscle actin, synaptophysin, CD117, CD45, myogenin, CAM5.2, pancytokeratin, WT1, EMA, CD99, neurofilament, CD34 and p53. Ki67 showed a low proliferative activity. Electron microscopy showed focal rhabdoid differentiation. However, INI-1 (SNF-5/BAF47) demonstrated preservation of nuclear positivity in the neoplastic cells. Cytogenetic studies showed translocation t(11;22)(p13;q12) confirming an EWSR1-WT1 translocation characteristic for DSRCT, and t(1;15)(q11;p11.2) of unknown significance. This case is a diagnostic challenge because of atypical immunohistochemical profile and cytogenetic study is crucial in rendering the correct diagnosis. PMID- 25133150 TI - Resolution of hemolysis from pump thrombus during left ventricular assist device exchange. AB - A 50-year-old male who underwent a HeartMate II left ventricular assist device placement for ischemic cardiomyopathy presented with discolored urine and hemolysis 3 mo after the operation. His hemolysis was thought to be due to thrombosis within the pump. Imaging studies were not able to visualize a left ventricular thrombus. Medical management with anticoagulation failed and he underwent surgery for a pump exchange. Intraoperatively, a firm thrombus was found within the pump of the HeartMate II, and the color of the urine changed dramatically from cola-colored to yellow which enabled us to confirm the diagnosis. PMID- 25133151 TI - Transthoracic echo: A sensitive tool for detecting cardiac extension of renal cell carcinoma? AB - Renal cell carcinoma is a common urological malignancy with the unique ability to invade the inferior vena cava (IVC) and to extend into the right atrium of the heart. Of those with Renal cell carcinoma only 4%-25% are found to have IVC invasion and of those only 2%-10% extend into the right atrium. If treated surgically, extension of tumor thrombus is not a determinant of survival; therefore it is imperative to determine the presence and extent of tumor thrombus in order to determine surgical approach and tumor resection. To date this has been primarily accomplished by magnetic resonance imaging and computed tomography. We present a case of 61 years old African American woman in which transthoracic echocardiography provided a more accurate determination/characterization of the presence and degree of tumor thrombus and extension. PMID- 25133152 TI - Prucalopride-associated acute tubular necrosis. AB - We report the first case of acute renal failure secondary to prucalopride, a novel agent for the treatment of chronic constipation. The 75 years old male patient was initiated on prucalopride after many failed treatments for constipation following a Whipple's procedure for pancreatic cancer. Within four months of treatment his creatinine rose from 103 to 285 MUmol/L (eGFR 61 decrease to 19 mL/min per 1.73 m(2)). He was initially treated with prednisone for presumed acute interstitial nephritis as white blood casts were seen on urine microscopy. When no improvement was detected, a core biopsy was performed and revealed interstitial fibrosis and tubular atrophy. The presence of oxalate and calcium phosphate crystals were also noted. These findings suggest acute tubular necrosis which may have been secondary to acute interstitial nephritis or hemodynamic insult. The use of prednisone may have suppressed signs of inflammation and therefore the clinical diagnosis was deemed acute interstitial nephritis causing acute tubular necrosis. There are no previous reports of prucalopride associated with acute renal failure from the literature, including previous Phase II and III trials. PMID- 25133153 TI - Actinic prurigo of the lip: Two case reports. AB - Actinic prurigo is a photodermatosis that can affect the skin, conjunctiva and lips. It is caused by an abnormal reaction to sunlight and is more common in high altitude living people, mainly in indigenous descendants. The diagnosis of actinic prurigo can be challenging, mainly when lip lesions are the only manifestation, which is not a common clinical presentation. The aim of this article is to report two cases of actinic prurigo showing only lip lesions. The patients were Afro-American and were unaware of possible Indian ancestry. Clinical exam, photographs, videoroscopy examination and biopsy were performed, and the diagnosis of actinic prurigo was established. Topical corticosteroid and lip balm with ultraviolet protection were prescribed with excellent results. The relevance of this report is to show that although some patients may not demonstrate the classical clinical presentation of actinic prurigo, the associated clinical and histological exams are determinants for the correct diagnosis and successful treatment of this disease. PMID- 25133154 TI - Appendicitis in double cecal appendix: Case report. AB - Double cecal appendix is a rare anatomical variation. Approximately 100 cases have been reported worldwide. It is usually diagnosed incidentally during emergency appendectomies due to inflammatory processes in the cecal appendix. CASE PRESENTATION: male, white, 36 years old, obese, presenting with pain in the lower abdomen for 24 h followed by nausea, vomiting and mild fever. He was subjected to additional tests, with the leukogram showing leukocytosis and abdominal ultrasonography depicting cecal appendix with thickened wall, locally associated with small quantities of liquid and intestinal loop obstruction. He underwent laparotomy, revealing acute appendicitis. Another intestinal loop obstruction was identified next to the ileum, leading to recognizing another cecal appendix after local dissection. Double appendectomy and segmental iliectomy were performed although not needed. Results of the anatomopathological examination of the surgical samples showed acute inflammation in the two cecal appendices. So, performing a routine retroperitoneal release and a complete cecum evaluation during such surgical procedures is recommended and suggested due to the possibility of not identifying a second cecal appendix. PMID- 25133155 TI - Rare large homozygous CFTR gene deletion in an Iranian patient with cystic fibrosis. AB - Cystic fibrosis, a common autosomal recessive genetic disorder among Caucasians, is caused by defects in the transmembrane conductance regulatory (CFTR) gene. The analysis of CFTR gene mutations is useful to better characterize the disease, and for preconceptional screening, prenatal and preimplantation genetic diagnosis. Here we report the results of a genetic analysis in a 16-year-old boy from southwestern Iran diagnosed as having cystic fibrosis in infancy based on gastrointestinal and pulmonary manifestations, with positive sweat chloride tests. He lacked both normal and mutant forms of the fragment corresponding to the ?F508 allele in initial genetic studies. Multiplex ligation-dependent probe amplification-based testing revealed a homozygous deletion spanning exons 4 to 10 of the CFTR gene. We predict an in-frame deletion removing 373 amino acids based on our sequencing results. Determining CFTR gene mutations in patients and their family members would be helpful to prevent the occurrence of new cases, especially in populations in which consanguinity is common. PMID- 25133156 TI - Gastric conduit perforation. AB - As patients with carcinoma of the esophagus live longer, complications associated with the use of a gastric conduit are increasing. Ulcers form in the gastric conduit in 6.6% to 19.4% of patients. There are a few reports of perforation of a gastric conduit in the English literature. Almost all of these were associated with serious complications. We report a patient who developed a tension pneumothorax consequent to spontaneous perforation of an ulcer in the gastric conduit 7 years after the index surgery in a patient with carcinoma of the gastroesophageal junction. He responded well to conservative management. Complications related to a gastric conduit can be because of multiple factors. Periodic endoscopic surveillance of gastric conduits should be considered as these are at a higher risk of ulcer formation than a normal stomach. Long term treatment with proton pump inhibitors may decrease complications. There are no guidelines for the treatment of a perforated gastric conduit ulcer and the management should be individualized. PMID- 25133158 TI - Circuit models and experimental noise measurements of micropipette amplifiers for extracellular neural recordings from live animals. AB - Glass micropipettes are widely used to record neural activity from single neurons or clusters of neurons extracellularly in live animals. However, to date, there has been no comprehensive study of noise in extracellular recordings with glass micropipettes. The purpose of this work was to assess various noise sources that affect extracellular recordings and to create model systems in which novel micropipette neural amplifier designs can be tested. An equivalent circuit of the glass micropipette and the noise model of this circuit, which accurately describe the various noise sources involved in extracellular recordings, have been developed. Measurement schemes using dead brain tissue as well as extracellular recordings from neurons in the inferior colliculus, an auditory brain nucleus of an anesthetized gerbil, were used to characterize noise performance and amplification efficacy of the proposed micropipette neural amplifier. According to our model, the major noise sources which influence the signal to noise ratio are the intrinsic noise of the neural amplifier and the thermal noise from distributed pipette resistance. These two types of noise were calculated and measured and were shown to be the dominating sources of background noise for in vivo experiments. PMID- 25133159 TI - Some physicochemical remarks on spontaneous emulsification of vitreal tamponades. AB - The importance of gravitational instability in determining the emulsification of vitreal tamponades is discussed. Theoretical results and numerical simulations indicate that the spontaneous formation of water-silicon oil is a rare event and that the very low concentration of surface active agents cannot justify the systematic formation of emulsions. The gravitational instabilities seem to play the main role. Our theoretical results seem in agreement with the experimental evidences; furthermore they indicate a future research line for the improvement of endotamponades. Indeed, the use of biodegradable antifoam may avoid the formation of bubbles and delay the formation of emulsions. PMID- 25133157 TI - Postactivation potentiation biases maximal isometric strength assessment. AB - Postactivation potentiation (PAP) is known to enhance force production. Maximal isometric strength assessment protocols usually consist of two or more maximal voluntary isometric contractions (MVCs). The objective of this study was to determine if PAP would influence isometric strength assessment. Healthy male volunteers (n = 23) performed two five-second MVCs separated by a 180-seconds interval. Changes in isometric peak torque (IPT), time to achieve it (tPTI), contractile impulse (CI), root mean square of the electromyographic signal during PTI (RMS), and rate of torque development (RTD), in different intervals, were measured. Significant increases in IPT (240.6 +/- 55.7 N.m versus 248.9 +/- 55.1 N.m), RTD (746 +/- 152 N.m.s(-1) versus 727 +/- 158 N.m.s(-1)), and RMS (59.1 +/- 12.2% RMSMAX versus 54.8 +/- 9.4% RMSMAX) were found on the second MVC. tPTI decreased significantly on the second MVC (2373 +/- 1200 ms versus 2784 +/- 1226 ms). We conclude that a first MVC leads to PAP that elicits significant enhancements in strength-related variables of a second MVC performed 180 seconds later. If disconsidered, this phenomenon might bias maximal isometric strength assessment, overestimating some of these variables. PMID- 25133161 TI - The bacterial contamination of allogeneic bone and emergence of multidrug resistant bacteria in tissue bank. AB - Present study was carried out for the microbiological evaluation of allogeneic bone processed from femoral heads. A total 60 bacterial isolates comprising five different species including Streptococcus spp., Staphylococcus spp., Klebsiella spp., Bacillus spp., and Pseudomonas spp. were characterized based on their cultural and biochemical characteristics. Average bioburden was ranged from 5.7 * 10(1) to 3.9 * 10(4) cfu/gm. The majority (81.7%) of the microbial contaminants were detected as Gram positive with the predominant organism being skin commensal coagulase negative Staphylococci (43.3%). Antimicrobial resistance was evaluated by the activities of 14 broad and narrow spectrum antibiotic discs. Comparing the overall pattern, marked resistance was noted against Penicillin and Amoxicillin 100% (60/60). The most effective single antibiotics were Gentamicin, Tobramycin, and Ofloxacin which were bactericidal against 100% (60/60) isolates. Multidrug resistance (MDR) was confirmed in 70% (42/60) of the samples. Among them, the most prevalent antibiotypes were Penicillin, Amoxicillin, Oxacillin, Polymyxin, and Cefpodoxime (80% of total MDR). The study results revealed higher contamination rate on bone allografts and recommend the implementation of good tissue banking practices during tissue procurement, processing, and storage in order to minimize the chances of contamination. PMID- 25133160 TI - The role of neurotrophic factors conjugated to iron oxide nanoparticles in peripheral nerve regeneration: in vitro studies. AB - Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half-life of few minutes. In order to prolong their activity, we have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve growth factor (betaNGF), glial cell-derived neurotrophic factor (GDNF), and basic fibroblast growth factor (FGF-2). Comparative stability studies of free versus conjugated factors revealed that the conjugated neurotrophic factors were significantly more stable in tissue cultures and in medium at 37 degrees C. The biological effects of free versus conjugated neurotrophic factors were examined on organotypic dorsal root ganglion (DRG) cultures performed in NVR-Gel, composed mainly of hyaluronic acid and laminin. Results revealed that the conjugated neurotrophic factors enhanced early nerve fiber sprouting compared to the corresponding free factors. The most meaningful result was that conjugated-GDNF, accelerated the onset and progression of myelin significantly earlier than the free GDNF and the other free and conjugated factors. This is probably due to the beneficial and long-acting effect that the stabilized conjugated-GDNF had on neurons and Schwann cells. These conclusive results make NVR-Gel enriched with conjugated-GDNF, a desirable scaffold for the reconstruction of severed peripheral nerve. PMID- 25133162 TI - Hypoxia-pretreated human MSCs attenuate acute kidney injury through enhanced angiogenic and antioxidative capacities. AB - Hypoxia preconditioning has been confirmed as an effective strategy to enhance the therapeutic potentials of mesenchymal stem cells (MSCs), such as for myocardial ischemia. However, whether hypoxia preconditioning would produce beneficial effects on MSC-based renal repair has not been demonstrated. In the study, we aimed to determine the feasibility and efficacy of hypoxia preconditioning to enhance MSC-based therapy of acute kidney injury (AKI). MSCs were isolated from human adipose tissues. The paracrine effects of MSCs under normoxia and hypoxia were determined in vitro. Rats of AKI were induced by kidney I/R surgery and randomly divided into three groups: I/R control receiving PBS injection; MSC group receiving normal MSC injection; hypoMSC group receiving hypoxia-preconditioned MSC injection. It was demonstrated in vitro that paracrine effects of MSCs were significantly enhanced, especially angiogenic factors. Dihydroethidium (DHE) staining showed that antioxidative activities of MSCs were significantly enhanced by hypoxia stimulation. Vascularization, apoptosis, and histological injury were all significantly improved in hypoMSC injected group compared with that in control and MSC injected groups. Finally, the renal function was also significantly improved in hypoMSC injected group compared with that in the other two groups as assessed by the serum creatinine and BUN levels. PMID- 25133163 TI - Identification of modules related to programmed cell death in CHD based on EHEN. AB - The formation and death of macrophages and foam cells are one of the major factors that cause coronary heart disease (CHD). In our study, based on the Edinburgh Human Metabolic Network (EHMN) metabolic network, we built an enzyme network which was constructed by enzymes (nodes) and reactions (edges) called the Edinburgh Human Enzyme Network (EHEN). By integrating the subcellular location information for the reactions and refining the protein-reaction relationships based on the location information, we proposed a computational approach to select modules related to programmed cell death. The identified module was in the EHEN mitochondria (EHEN-M) and was confirmed to be related to programmed cell death, CHD pathogenesis, and lipid metabolism in the literature. We expected this method could analyze CHD better and more comprehensively from the point of programmed cell death in subnetworks. PMID- 25133164 TI - Consumption of green coffee reduces blood pressure and body composition by influencing 11beta-HSD1 enzyme activity in healthy individuals: a pilot crossover study using green and black coffee. AB - Dietary polyphenols may have a protective role against the development of CVD. Thus, we aimed to investigate the effects of green coffee (GC), rich in chlorogenic acid, and black coffee (BC) on cardiovascular markers. A randomised pilot crossover study was performed on healthy subjects who consumed both coffees for 2 weeks. We measured anthropometry, blood pressure, and arterial elasticity after each intervention and collected urine samples to monitor antioxidant capacity. Free cortisol and cortisone levels were obtained from urine and analysed by specific ELISA methods. Systolic blood pressure (P = 0.018) and arterial elasticity (P = 0.001) were significantly reduced after GC. BMI (P = 0.04 for BC; P = 0.01 for GC) and abdominal fat (P = 0.01 for BC; P = 0.009 for GC) were also significantly reduced with no changes in energy intake. Urinary free cortisol was significantly reduced from 125.6 +/- 85.9 nmol/day to 76.0 +/- 54.9 nmol/day following GC and increased to 132.1 +/- 89.1 nmol/day after BC. Urinary free cortisone increased by 18% following BC and 9% following GC (nonsignificant). Cortisol/cortisone ratio (indicating 11beta-HSD1 activity) was reduced after GC (from 3.5 +/- 1.9 to 1.7 +/- 1.04, P = 0.002). This suggests that GC can play a role in reducing cardiovascular risk factors. Further research including hypertensive and overweight individuals will now be justified to clarify whether GC could have a therapeutic role in CVD. PMID- 25133165 TI - Factors associated with spontaneous clearance of hepatitis C virus in Chinese population. AB - Hepatitis C virus (HCV) infections spontaneously clear in approximately 15-45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype. PMID- 25133166 TI - Dabigatran in secondary stroke prevention: clinical experience with 106 patients. AB - INTRODUCTION: Our aim was to analyze our clinical experience with dabigatran etexilate in secondary stroke prevention. METHODS: We retrospectively included patients starting dabigatran etexilate for secondary stroke prevention from March 2010 to December 2012. Efficacy and safety variables were registered. RESULTS: 106 patients were included, median follow-up of 12 months (range 1-31). Fifty-six females (52.8%), mean age 76.4 (range 50-95, SD 9.8), median CHADS2 4 (range 2 6), CHA2DS2-VASc 5 (range 2-9), and HAS-BLED 2 (range 1-5). Indication for dabigatran etexilate was ischemic stroke in 101 patients and acute cerebral hemorrhage (CH) due to warfarin in 5 (4.7%). Dabigatran etexilate 110 mg bid was prescribed in 71 cases (67%) and 150 mg bid was prescribed in the remaining. Seventeen patients (16%) suffered 20 complications during follow-up. Ischemic complications (10) were 6 transient ischemic attacks (TIA), 3 ischemic strokes, and 1 acute coronary syndrome. Hemorrhagic complications (10) were CH (1), gastrointestinal bleeding (6), mild hematuria (2), and mild metrorrhagia (1), leading to dabigatran etexilate discontinuation in 3 patients. Patients with previous CH remained uneventful. Three patients died (pneumonia, congestive heart failure, and acute cholecystitis) and 9 were lost during follow-up. CONCLUSIONS: Dabigatran etexilate was safe and effective in secondary stroke prevention in clinical practice, including a small number of patients with previous history of CH. PMID- 25133167 TI - Serum osteopontin level correlates with carotid-femoral pulse wave velocity in geriatric persons. AB - Osteopontin (OPN) is involved in the regulation of vascular calcification processes. The aim of this study was to evaluate the relationship between fasting serum OPN concentration and carotid-femoral pulse wave velocity (cfPWV) in geriatric persons. Fasting blood samples were obtained from 93 geriatric persons. cfPWV were performed by SphygmoCor system. Serum OPN levels were measured using a commercially available enzyme-linked immunosorbent assay. Geriatric adults who had diabetes (P = 0.007) or dyslipidemia (P = 0.029) had higher cfPWV levels than those without diabetes or dyslipidemia. The univariable linear regression analysis showed that age (P = 0.002), waist circumference (P = 0.048), body mass index (P = 0.004), systolic blood pressure (P = 0.001), diastolic blood pressure (P = 0.036), pulse pressure (P = 0.017), creatinine (P = 0.002), and log-OPN level (P = 0.001) were positively correlated with cfPWV levels, while the high density lipoprotein cholesterol (HDL-cholesterol) level (P = 0.007) and glomerular filtration rate (P = 0.001) were negatively correlated with cfPWV levels among the geriatric adults. Multivariable forward stepwise linear regression analysis of the significant variables also showed that log-OPN (beta = 0.233, R (2) = 0.123, regression coefficient: 1.868, P = 0.011) was still an independent predictor of cfPWV levels in geriatric persons. PMID- 25133168 TI - Pharmaceutical options for triggering of final oocyte maturation in ART. AB - Since the pioneering days of in vitro fertilization, hCG has been the gold standard to induce final follicular maturation. We herein reviewed different pharmaceutical options for triggering of final oocyte maturation in ART. The new upcoming agent seems to be GnRHa with its potential advantages over hCG trigger. GnRHa triggering elicits a surge of gonadotropins resembling the natural midcycle surge of gonadotropins, without the prolonged action of hCG, resulting in the retrieval of more mature oocytes and a significant reduction in or elimination of OHSS as compared to hCG triggering. The induction of final follicular maturation using GnRHa represents a paradigm shift in the ovulation triggering concept in ART and, thus, a way to develop a safer IVF procedure. Kisspeptins are key central regulators of the neuroendocrine mechanisms of human reproduction, who have been shown to effectively elicit an LH surge and to induce final oocyte maturation in IVF cycles. This new trigger concept may, therefore, offer a completely new, "natural" pharmacological option for ovulation induction. Whether kisspeptins will be the future agent to trigger ovulation remains to be further explored. PMID- 25133169 TI - Cystic fibrosis and new trends by ophthalmological evaluation: a pilot study. AB - BACKGROUND: Cystic fibrosis (CF) is characterized by hypoxia that affects several organic tissues. Retinal ganglion cells may suffer from the hypoxic status, and this may lead to alterations of retinal nerve fiber. METHODS: Twenty-two eyes in CF patients were analyzed. A complete ocular evaluation and visual field exams of the 30 central degrees were performed using the frequency doubling technology (FDT). Forced expiratory volume in one second (FEV1%), forced vital capacity (FVC%), oxyhaemoglobin saturation (SpO2%), and hematocrit (Ht%) have been calculated. FDT analyzed parameters were mean deviation (MD) and pattern standard deviation (PSD). Pearson's correlation was chosen as statistical analysis. RESULTS: Data showed statistically significant relationship between MD and Ht% (r value -0.18; P = 0.04), MD and FEV1% (r value -0.68; P = 0.001), and MD and FVC% (r value -0.45; P = 0.005). Moreover, there were correlations between PSD and Ht% (r value 0.29; P = 0.03), PSD and SpO2% (r value -0.31; P = 0.01), PSD and FEV1% (r value 0.71; P = 0.0005), and PSD and FVC% (r value 0.63; P = 0.003). CONCLUSIONS: The oxygen supply alterations might determine hypoxia of the ganglion cells causing a decrease of receptive optic nerve fiber activity. This method could be also useful to evaluate indirectly pulmonary activity of the CF disease. PMID- 25133171 TI - UVA-UVB photoprotective activity of topical formulations containing Morinda citrifolia extract. AB - Exposure to solar radiation, particularly its ultraviolet (UV) component, has a variety of harmful effects on human health. Some of these effects include sunburn cell formations, basal and squamous cell cancers, melanoma, cataracts, photoaging of the skin, and immune suppression. The beneficial photoprotective effects of topical formulations with the extract, Morinda citrifolia, have not been investigated. This present study aims to investigate the potential benefits of M. citrifolia topical application on the dorsal skin of mice, exposed to UVA-UVB light. Using 7 days of treatment, [before (baseline values) and 20 h after UV exposure], the thickness, skin barrier damage (TEWL), erythema, and histological alterations were evaluated. The results showed that the formulations containing the extract protected the skin against UV-induced damage. PMID- 25133172 TI - Biomarkers in women's cancers, gynecology, and obstetrics. PMID- 25133170 TI - Intra-QT spectral coherence as a possible noninvasive marker of sustained ventricular tachycardia. AB - Sudden cardiac death is the main cause of mortality in patients affected by chronic heart failure (CHF) and with history of myocardial infarction. No study yet investigated the intra-QT phase spectral coherence as a possible tool in stratifying the arrhythmic susceptibility in patients at risk of sudden cardiac death (SCD). We, therefore, assessed possible difference in spectral coherence between the ECG segment extending from the q wave to the T wave peak (QTp) and the one from T wave peak to the T wave end (Te) between patients with and without Holter ECG-documented sustained ventricular tachycardia (VT). None of the QT variability indexes as well as most of the coherences and RR power spectral variables significantly differed between the two groups except for the QTp-Te spectral coherence. The latter was significantly lower in patients with sustained VT than in those without (0.508 +/- 0.150 versus 0.607 +/- 0.150, P < 0.05). Although the responsible mechanism remains conjectural, the QTp-Te spectral coherence holds promise as a noninvasive marker predicting malignant ventricular arrhythmias. PMID- 25133173 TI - Molecular epidemiology of genogroup II noroviruses infection in outpatients with acute gastroenteritis in Nanjing, China (2010-2013). AB - OBJECTIVE: Human noroviruses (NoVs) of genogroup II are the most common strains detected in sporadic cases of acute nonbacterial gastroenteritis in outpatients in Nanjing. To gain insight into the molecular epidemiology of GII strains, we analyzed 75 positive NoV cases from 2010 to 2013. METHODS: The sporadic cases were detected by real-time PCR with specific primers and probes to human NoVs of genogroup I or II, human sapovirus, human rotavirus, human astrovirus, and human enteric adenovirus. Human NoVs of genogroup II were further studied by VP1 amplification (RT- PCR), cloning, sequencing, and phylogenetic analysis. RESULTS: Rotavirus and human NoVs were more frequently detected in all the cases from 2010 to 2013. Human NoVs infection was more frequent since 2011 and more frequent than rotavirus infection after 2012. Out of the 75 NoV cases of genogroup II, there were 5 GII.6, 11 GII.3, and 59 GII.4. Of the 59 GII.4, 27 cases were previous GII.4.2006b strains that circulated between 2010 and 2012; while 32 cases were the newly emerging GII.4 strains GII.4.2012 from 2011 to 2013. CONCLUSION: Our data confirm other studies on the rapid emergence and displacement of highly virulent GII.4 strains. PMID- 25133175 TI - Adrenergic activation of melatonin secretion in ovine pineal explants in short term superfusion culture occurs via protein synthesis independent and dependent phenomena. AB - The ovine pineal is generally considered as an interesting model for the study on adrenergic regulation of melatonin secretion due to some functional similarities with this gland in the human. The present investigations, performed in the superfusion culture of pineal explants, demonstrated that the norepinephrine induced elevation of melatonin secretion in ovine pinealocytes comprised of two subsequent periods: a rapid increase phase and a slow increase phase. The first one included the quick rise in release of N-acetylserotonin and melatonin, occurring parallel to elevation of NE concentration in the medium surrounding explants. This rapid increase phase was not affected by inhibition of translation. The second, slow increase phase began after NE level had reached the maximum concentration in the culture medium and lasted about two hours. It was completely abolished by the treatment with translation inhibitors. The obtained results showed for the first time that the regulation of N-acetylserotonin synthesis in pinealocytes of some species like the sheep involves the on/off mechanism, which is completely independent of protein synthesis and works very fast. They provided strong evidence pointing to the need of revision of the current opinion that arylalkylamines N-acetyltransferase activity in pinealocytes is controlled exclusively by changes in enzyme abundance. PMID- 25133174 TI - Sphingosine-1-phosphate transporters as targets for cancer therapy. AB - Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that regulates cell survival, migration, the recruitment of immune cells, angiogenesis, and lymphangiogenesis, all of which are involved in cancer progression. S1P is generated inside cancer cells by sphingosine kinases then exported outside of the cell into the tumor microenvironment where it binds to any of five G protein coupled receptors and proceeds to regulate a variety of functions. We have recently reported on the mechanisms underlying the "inside-out" signaling of S1P, its export through the plasma membrane, and its interaction with cell surface receptors. Membrane lipids, including S1P, do not spontaneously exchange through lipid bilayers since the polar head groups do not readily go through the hydrophobic interior of the plasma membrane. Instead, specific transporter proteins exist on the membrane to exchange these lipids. This review summarizes what is known regarding S1P transport through the cell membrane via ATP-binding cassette transporters and the spinster 2 transporter and discusses the roles for these transporters in cancer and in the tumor microenvironment. Based on our research and the emerging understanding of the role of S1P signaling in cancer and in the tumor microenvironment, S1P transporters and S1P signaling hold promise as new therapeutic targets for cancer drug development. PMID- 25133176 TI - Sensoric protection after median nerve injury: babysitter-procedure prevents muscular atrophy and improves neuronal recovery. AB - The babysitter-procedure might offer an alternative when nerve reconstruction is delayed in order to overcome muscular atrophy due to denervation. In this study we aimed to show that a sensomotoric babysitter-procedure after median nerve injury is capable of preserving irreversible muscular atrophy. The median nerve of 20 female Wistar rats was denervated. 10 animals received a sensory protection with the N. cutaneous brachii. After six weeks the median nerve was reconstructed by autologous nerve grafting from the contralateral median nerve in the babysitter and the control groups. Grasping tests measured functional recovery over 15 weeks. At the end of the observation period the weight of the flexor digitorum sublimis muscle was determined. The median nerve was excised for histological examinations. Muscle weight (P < 0.0001) was significantly superior in the babysitter group compared to the control group at the end of the study. The histological evaluation revealed a significantly higher diameter of axons (P = 0.0194), nerve fiber (P = 0.0409), and nerve surface (P = 0.0184) in the babysitter group. We conclude that sensory protection of a motor nerve is capable of preserving muscule weight and we may presume that metabolism of the sensory nerve was sufficient to keep the target muscle's weight and vitality. PMID- 25133177 TI - Comparison of the effects of low volume prilocaine and alkalinized prilocaine for the regional intravenous anesthesia technique in hand and wrist surgery. AB - AIM: Comparing the effectivity of prilocaine and prilocaine alkalinized with 8.4% NaHCO3 in terms of sensory and motor block onset and termination durations in RIVA technique considering patients' satisfaction and tolerance with application of tourniquet undergoing hand-wrist surgery. MATERIALS AND METHODS: 64 patients were randomised into two groups. First group (Group P) was administered prilocaine and second group (Group PN) was administered prilocaine + %8.4 NaHCO3. Sensory and motor block onset and termination times and onset of tourniquet pain were recorded. RESULTS: No significant difference was found between the two groups in terms of onset and termination of sensory block and the onset of motor block. The duration of the motor block was longer in Group PN than in Group P (P < 0.05). Tourniquet pain was more intense in Group P (P = 0.036). In Group PN, the use of additional drugs was recorded at a lower rate and patients' satisfaction was higher than Group P. CONCLUSION: In the present study, it was established that alkalinization of prilocaine had no effect on the duration of sensory block and it prolonged the duration of motor block, increased patients' satisfaction, and decreased tourniquet pain. It is our suggestion that future studies should be carried out on the issue by using different volumes. PMID- 25133178 TI - Physiological and biochemical changes in Brassica juncea plants under Cd-induced stress. AB - Plants of Brassica juncea L. var. RLC-1 were exposed for 30 days to different concentrations (0, 0.2, 0.4, and 0.6 mM) of cadmium (Cd) to analyze the Cd uptake, H2O2 content, hormonal profiling, level of photosynthetic pigments (chlorophyll, carotenoid, and flavonoid), gaseous exchange parameters (photosynthetic rate, vapour pressure deficit, intercellular CO2 concentration, and intrinsic mesophyll rate), antioxidative enzymes (superoxide dismutase, polyphenol oxidase, glutathione-S transferase, and glutathione peroxidase), antioxidant assays (DPPH, ABTS, and total phenolic content), and polyphenols. Results of the present study revealed the increased H2O2 content and Cd uptake with increasing metal doses. UPLC analysis of plants showed the presence of various polyphenols. Gaseous exchange measurements were done by infrared gas analyzer (IRGA), which was negatively affected by metal treatment. In addition, LC/MS study showed the variation in the expression of plant hormones. Level of photosynthetic pigments and activities of antioxidative enzymes were altered significantly in response to metal treatment. In conclusion, the antioxidative defence system of plants got activated due to heavy metal stress, which protects the plants by scavenging free radicals. PMID- 25133180 TI - Analysis of EEG signals related to artists and nonartists during visual perception, mental imagery, and rest using approximate entropy. AB - In this paper, differences between multichannel EEG signals of artists and nonartists were analyzed during visual perception and mental imagery of some paintings and at resting condition using approximate entropy (ApEn). It was found that ApEn is significantly higher for artists during the visual perception and the mental imagery in the frontal lobe, suggesting that artists process more information during these conditions. It was also observed that ApEn decreases for the two groups during the visual perception due to increasing mental load; however, their variation patterns are different. This difference may be used for measuring progress in novice artists. In addition, it was found that ApEn is significantly lower during the visual perception than the mental imagery in some of the channels, suggesting that visual perception task requires more cerebral efforts. PMID- 25133179 TI - Metabolic variations, antioxidant potential, and antiviral activity of different extracts of Eugenia singampattiana (an endangered medicinal plant used by Kani tribals, Tamil Nadu, India) leaf. AB - Eugenia singampattiana is an endangered medicinal plant used by the Kani tribals of South India. The plant had been studied for its antioxidant, antitumor, antihyperlipidemic, and antidiabetic activity. But its primary and secondary metabolites profile and its antiviral properties were unknown, and so this study sought to identify this aspect in Eugenia singampattiana plant through different extraction methods along with their activities against porcine reproductive and respiratory syndrome virus (PRRSV). The GC-MS analysis revealed that 11 primary metabolites showed significant variations among the extracts. Except for fructose all other metabolites were high with water extract. Among 12 secondary metabolites showing variations, the levels of 4-hydroxy benzoic acid, caffeic acid, rutin, ferulic acid, coumaric acid, epigallocatechin gallate, quercetin, myricetin, and kaempferol were high with methanol extract. Since the flavonoid content of methanol extracts was high, the antioxidant potential, such as ABTS, and phosphomolybdenum activity increased. The plants antiviral activity against PRRSV was for the first time confirmed and the results revealed that methanol 25 ug and 75 to 100 ug in case of water extracts revealed antiviral activity. PMID- 25133182 TI - Novel psychoactive substances in young adults with and without psychiatric comorbidities. AB - OBJECTIVE: Comorbidities between psychiatric diseases and consumption of traditional substances of abuse (alcohol, cannabis, opioids, and cocaine) are common. Nevertheless, there is no data regarding the use of novel psychoactive substances (NPS) in the psychiatric population. The purpose of this multicentre survey is to investigate the consumption of a wide variety of psychoactive substances in a young psychiatric sample and in a paired sample of healthy subjects. METHODS: A questionnaire has been administered, in different Italian cities, to 206 psychiatric patients aged 18 to 26 years and to a sample of 2615 healthy subjects matched for sex, gender, and living status. RESULTS: Alcohol consumption was more frequent in the healthy young population compared to age matched subjects suffering from mental illness (79.5% versus 70.7%; P < 0.003). Conversely, cocaine and NPS use was significantly more common in the psychiatric population (cocaine 8.7% versus 4.6%; P = 0.002) (NPS 9.8% versus 3%; P < 0.001). CONCLUSIONS: The use of novel psychoactive substances in a young psychiatric population appears to be a frequent phenomenon, probably still underestimated. Therefore, careful and constant monitoring and accurate evaluations of possible clinical effects related to their use are necessary. PMID- 25133183 TI - Upregulation of relaxin after experimental subarachnoid hemorrhage in rabbits. AB - BACKGROUND: Although relaxin causes vasodilatation in systemic arteries, little is known about its role in cerebral arteries. We investigated the expression and role of relaxin in basilar arteries after subarachnoid hemorrhage (SAH) in rabbits. METHODS: Microarray analysis with rabbit basilar artery RNA was performed. Messenger RNA expression of relaxin-1 and relaxin/insulin-like family peptide receptor 1 (RXFP1) was investigated with quantitative RT-PCR. RXFP1 expression in the basilar artery was investigated with immunohistochemistry. Relaxin concentrations in cerebrospinal fluid (CSF) and serum were investigated with an enzyme-linked immunosorbent assay. Using human brain vascular smooth muscle cells (HBVSMC) preincubated with relaxin, myosin light chain phosphorylation (MLC) was investigated with immunoblotting after endothelin-1 stimulation. RESULTS: After SAH, RXFP1 mRNA and protein were significantly downregulated on day 3, whereas relaxin-1 mRNA was significantly upregulated on day 7. The relaxin concentration in CSF was significantly elevated on days 5 and 7. Pretreatment with relaxin reduced sustained MLC phosphorylation induced by endothelin-1 in HBVSMC. CONCLUSION: Upregulation of relaxin and downregulation of RXFP1 after SAH may participate in development of cerebral vasospasm. Downregulation of RXFP1 may induce a functional decrease in relaxin activity during vasospasm. Understanding the role of relaxin may provide further insight into the mechanisms of cerebral vasospasm. PMID- 25133185 TI - Amino-functionalization of carbon nanotubes by using a factorial design: human cardiac troponin T immunosensing application. AB - A simple amino-functionalization method for carbon nanotubes and its application in an electrochemical immunosensor for detection of the human cardiac troponin T are described. Amino-functionalized carbon nanotubes allow oriented antibodies immobilization via their Fc regions, improving the performance of an immunosensor. Herein multiwalled carbon nanotubes were amino-functionalized by using the ethylenediamine reagent and assays were designed by fractional factorial study associated with Doehlert matrix. Structural modifications in the carbon nanotubes were confirmed by Fourier transform infrared spectroscopy. After amino-functionalization the carbon nanotubes were attached to screen-printed carbon electrode and a sandwich-type immunoassay was performed for measuring the cardiac troponin T. The electrochemical measurements were obtained through hydrogen peroxide reaction with peroxidase conjugated to the secondary antibody. Under optimal conditions, troponin T immunosensor was evaluated in serum samples, which showed a broad linear range (0.02 to 0.32 ng mL(-1)) and a low limit of detection, 0.016 ng mL(-1). This amino platform can be properly used as clinical tool for cardiac troponin T detection in the acute myocardial infarction diagnosis. PMID- 25133186 TI - Anti-inflammatory effect and mechanism of the green fruit extract of Solanum integrifolium Poir. AB - The green fruit of Solanum integrifolium Poir. has been used traditionally as an anti-inflammatory and analgesic remedy in Taiwanese aboriginal medicine. The goal of this study is to evaluate the anti-inflammatory activity and mechanism of the green fruit extract of S. integrifolium. A bioactivity-guided fractionation procedure was developed to identify the active partition fraction. The methanol fraction (ME), with the highest phenolic content, exhibited the strongest inhibitory effect against LPS-mediated nitric oxide (NO) release and cytotoxicity in RAW264.7 macrophages. ME also significantly downregulated the expression of LPS-induced proinflammatory genes, such as iNOS, COX-2, IL-1beta, IL-6, CCL2/MCP 1, and CCL3/MIP1alpha. Moreover, ME significantly upregulated HO-1 expression and stimulated the activation of extracellular-signal-regulated kinase 1/2 (ERK1/2). Pretreatment of cells with the HO-1 inhibitor zinc protoporphyrin and MEK/ERK inhibitor U0126 attenuated ME's inhibitory activity against LPS-induced NO production. Taken together, this is the first study to demonstrate the anti inflammatory activity of green fruit extract of S. integrifolium and its activity may be mediated by the upregulation of HO-1 expression and activation of ERK1/2 pathway. PMID- 25133184 TI - Behavioral and psychological symptoms in Alzheimer's disease. AB - Neuropsychiatric symptoms (NPS) such as depression, apathy, aggression, and psychosis are now recognized as core features of Alzheimer's disease (AD), and there is a general consensus that greater symptom severity is predictive of faster cognitive decline, loss of independence, and even shorter survival. Whether these symptoms result from the same pathogenic processes responsible for cognitive decline or have unique etiologies independent of AD-associated neurodegeneration is unclear. Many structural and metabolic features of the AD brain are associated with individual neuropsychiatric symptoms or symptom clusters. In addition, many genes have been identified and confirmed that are associated with symptom risk in a few cases. However, there are no single genes strongly predictive of individual neuropsychiatric syndromes, while functional and structural brain changes unique to specific symptoms may reflect variability in progression of the same pathological processes. Unfortunately, treatment success for these psychiatric symptoms may be lower when comorbid with AD, underscoring the importance of future research on their pathobiology and treatment. This review summarizes some of the most salient aspects of NPS pathogenesis. PMID- 25133188 TI - Gravity affects the closure of the traps in Dionaea muscipula. AB - Venus flytrap (Dionaea muscipula Ellis) is a carnivorous plant known for its ability to capture insects thanks to the fast snapping of its traps. This fast movement has been long studied and it is triggered by the mechanical stimulation of hairs, located in the middle of the leaves. Here we present detailed experiments on the effect of microgravity on trap closure recorded for the first time during a parabolic flight campaign. Our results suggest that gravity has an impact on trap responsiveness and on the kinetics of trap closure. The possible role of the alterations of membrane permeability induced by microgravity on trap movement is discussed. Finally we show how the Venus flytrap could be an easy and effective model plant to perform studies on ion channels and aquaporin activities, as well as on electrical activity in vivo on board of parabolic flights and large diameter centrifuges. PMID- 25133187 TI - Molecular mechanisms for biliary phospholipid and drug efflux mediated by ABCB4 and bile salts. AB - On the canalicular membranes of hepatocytes, several ABC transporters are responsible for the secretion of bile lipids. Among them, ABCB4, also called MDR3, is essential for the secretion of phospholipids from hepatocytes into bile. The biliary phospholipids are associated with bile salts and cholesterol in mixed micelles, thereby reducing the detergent activity and cytotoxicity of bile salts and preventing cholesterol crystallization. Mutations in the ABCB4 gene result in progressive familial intrahepatic cholestasis type 3, intrahepatic cholestasis of pregnancy, low-phospholipid-associated cholelithiasis, primary biliary cirrhosis, and cholangiocarcinoma. In vivo and cell culture studies have demonstrated that the secretion of biliary phospholipids depends on both ABCB4 expression and bile salts. In the presence of bile salts, ABCB4 located in nonraft membranes mediates the efflux of phospholipids, preferentially phosphatidylcholine. Despite high homology with ABCB1, ABCB4 expression cannot confer multidrug resistance. This review summarizes our current understanding of ABCB4 functions and physiological relevance, and discusses the molecular mechanism for the ABCB4-mediated efflux of phospholipids. PMID- 25133190 TI - Compensatory mechanisms of pancreatic beta cells: insights into the therapeutic perspectives for diabetes. PMID- 25133189 TI - Harnessing the helminth secretome for therapeutic immunomodulators. AB - Helminths are the largest and most complex pathogens to invade and live within the human body. Since they are not able to outpace the immune system by rapid antigen variation or faster cell division or retreat into protective niches not accessible to immune effector mechanisms, their long-term survival depends on influencing and regulating the immune responses away from the mode of action most damaging to them. Immunologists have focused on the excretory and secretory products that are released by the helminths, since they can change the host environment by modulating the immune system. Here we give a brief overview of the helminth-associated immune response and the currently available helminth secretome data. We introduce some major secretome-derived immunomodulatory molecules and describe their potential mode of action. Finally, the applicability of helminth-derived therapeutic proteins in the treatment of allergic and autoimmune inflammatory disease is discussed. PMID- 25133191 TI - Chicken embryos as a potential new model for early onset type I diabetes. AB - Diabetic retinopathy (DR) is the leading cause of blindness among the American working population. The purpose of this study is to establish a new diabetic animal model using a cone-dominant avian species to address the distorted color vision and altered cone pathway responses in prediabetic and early diabetic patients. Chicken embryos were injected with either streptozotocin (STZ), high concentration of glucose (high-glucose), or vehicle at embryonic day 11. Cataracts occurred in varying degrees in both STZ- and high glucose-induced diabetic chick embryos at E18. Streptozotocin-diabetic chicken embryos had decreased levels of blood insulin, glucose transporter 4 (Glut4), and phosphorylated protein kinase B (pAKT). In STZ-injected E20 embryos, the ERG amplitudes of both a- and b-waves were significantly decreased, the implicit time of the a-wave was delayed, while that of the b-wave was significantly increased. Photoreceptors cultured from STZ-injected E18 embryos had a significant decrease in L-type voltage-gated calcium channel (L-VGCC) currents, which was reflected in the decreased level of L-VGCCalpha1D subunit in the STZ-diabetic retinas. Through these independent lines of evidence, STZ-injection was able to induce pathological conditions in the chicken embryonic retina, and it is promising to use chickens as a potential new animal model for type I diabetes. PMID- 25133192 TI - Association of serum vaspin and adiponectin levels with renal function in patients with or without type 2 diabetes mellitus. AB - Vaspin and adiponectin are two adipocytokines with antidiabetic effects. Some studies reported that levels of adiponectin and vaspin were correlated with decreased glomerular filtration rate (FGR) and increased albuminuria. We therefore evaluated the vaspin and adiponectin levels in renal insufficiency (RI) patients with or without T2DM. Serum vaspin, adiponectin levels were measured in 416 subjects with or without T2DM. Analysis was made between groups divided by these subjects presence or absence of RI. We found that serum adiponectin level was significantly higher in nondiabetic patients with RI than in nondiabetic subjects without RI; however, there were no statistical differences between the diabetic patients with RI and without RI. In all the subjects, the serum adiponectin level was also higher in 50 individuals with RI than that in 366 subjects without RI. The serum vaspin levels showed no significant differences between the diabetic patients or nondiabetics subjects with RI and without RI. Contrary to adiponectin, the serum vaspin level was lower in 169 patients with T2DM than in 247 individuals without T2DM. Our data suggested that both of T2DM and renal insufficiency were correlated with the serum level of adiponectin. However, the serum vaspin levels showed no significant difference between the individuals with renal insufficiency and without renal insufficiency. PMID- 25133193 TI - Tribbles 3 regulates the fibrosis cytokine TGF- beta 1 through ERK1/2-MAPK signaling pathway in diabetic nephropathy. AB - To reveal the expression and possible role of tribbles homolog 3 (TRB3) in the incidence of type 2 diabetic nephropathy, we used immunohistochemistry, real-time quantitative PCR, western blot analysis, and enzyme-linked immunosorbent assay (ELISA) to study the expression of TRB3, extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK), transforming growth factor beta1 (TGF-beta1), and collagen type IV in kidneys of db/db diabetic mice and in murine renal mesangial cells stimulated with high glucose. The expression of TRB3, TGF-beta1, and collagen type IV was increased in kidneys of db/db diabetic mice. TGF-beta1 and collagen type IV regulated by high glucose through ERK1/2 MAPK were downregulated by silencing TRB3 in renal mesangial cells. TRB3 may be involved in diabetic nephropathy by regulating the fibrosis cytokine TGF-beta1 and collagen type IV through the ERK1/2 MAPK signaling pathway. PMID- 25133194 TI - Activation effects of polysaccharides of Flammulina velutipes mycorrhizae on the T lymphocyte immune function. AB - Flammulina velutipes mycorrhizae have increasingly been produced with increasing of F. velutipes production. A mouse model was thus used to examine potential effect of F. velutipes mycorrhizae on the immune function. Fifty female Wistar mice (5-weeks-old) weighed 15-20 g were randomly allocated into five groups. Polysaccharide of F. velutipes mycorrhizae were treated with mice and mice spleen lymphocytes. The levels of CD3(+), CD4(+), and CD8(+) T lymphocyte, interleukin-2 (IL-2), and tumor necrosis factor-a (TNF-alpha) were determined. The results showed that the proportions of CD3(+), and CD4(+) T lymphocyte, the ratio of CD4(+)/CD8(+), and the levels of IL-2 and TNF-a were significantly increased in polysaccharide of F. velutipes mycorrhizae, while the proportion of CD8(+) T lymphocyte was decreased in polysaccharide of F. velutipes mycorrhizae-dose dependent manner. Our findings indicated that a long term exposure of polysaccharide of F. velutipes mycorrhizae could activate the T lymphocyte immune function. Polysaccharide of F. velutipes mycorrhizae was expected to develop into the immune health products. PMID- 25133195 TI - Cardiovascular risk factors in the antiphospholipid syndrome. AB - A major cause of morbidity and mortality in the context of the antiphospholipid syndrome (APS) is the occurrence of thrombotic events. Besides the pathogenic roles of antiphospholipid antibodies (aPL), other risk factors and medical conditions, which are conditions for traditional risk of an individual without the APS, can coexist in this patient, raising their risk of developing thrombosis. Therefore, the clinical and laboratory investigation of comorbidities known to increase cardiovascular risk in patients with antiphospholipid antibody syndrome is crucial for the adoption of a more complete and effective treatment. Experimental models and clinical studies show evidence of association between APS and premature formation of atherosclerotic plaques. Atherosclerosis has major traditional risk factors: hypertension, diabetes mellitus, obesity, dyslipidemia, smoking, and sedentary lifestyle that may be implicated in vascular involvement in patients with APS. The influence of nontraditional risk factors as hyperhomocysteinemia, increased lipoprotein a, and anti-oxLDL in the development of thromboembolic events in APS patients has been studied in scientific literature. Metabolic syndrome with all its components also has been recently studied in antiphospholipid syndrome and is associated with arterial events. PMID- 25133196 TI - T CD3+CD8+ lymphocytes are more susceptible for apoptosis in the first trimester of normal human pregnancy. AB - AIMS: Normal human pregnancy is a complex process of many immunoregulatory mechanisms which protect fetus from the activation of the maternal immune system. The aim of the study was to investigate the apoptosis of lymphocytes in peripheral blood of normal pregnant patients and healthy nonpregnant women. METHODS: Sixty pregnant women and 17 nonpregnant women were included in the study. Lymphocytes were isolated and labeled with anti-CD3, anti-CD4, and anti CD8 monoclonal antibodies. Apoptosis was detected by CMXRos staining and analyzed using the flow cytometric method. RESULTS: We found significantly higher apoptosis of total lymphocytes in peripheral blood of pregnant patients when compared to healthy nonpregnant women. The percentage of apoptotic T CD3(+)CD8(+) cells in the first trimester was significantly higher when compared to the third trimester of normal pregnancy. The ratio of T CD3(+)CD4(+) : T CD3(+)CD8(+) apoptotic lymphocytes was significantly lower in the first trimester when compared to other trimesters of pregnancy and to both of the phases of the menstrual cycle. CONCLUSIONS: The higher apoptosis of T CD3(+)CD8(+) lymphocytes and the lower ratio of T CD3(+)CD4(+) : T CD3(+)CD8(+) apoptotic cells in the first trimester of normal pregnancy may suggest a higher susceptibility of T CD3(+)CD8(+) cells for apoptosis as a protective mechanism at the early stage of pregnancy. PMID- 25133197 TI - Clinical, laboratory, and therapeutic analyses of 21 patients with neonatal thrombosis and antiphospholipid antibodies: a literature review. AB - OBJECTIVES: A review of the literature reports neonatal thrombosis and antiphospholipid antibodies cases through a retrospective study that focuses on the pathogenesis and main clinical and laboratory manifestations of this disease. METHODS: The case reports were selected from PubMed. The keywords used to search were neonatal, antiphospholipid syndrome, thrombosis, and antiphospholipid antibodies. References that were published from 1987 to 2013 were reviewed. RESULTS: Twenty-one cases of neonatal thrombosis and antiphospholipid antibodies were identified. Ten children were born preterm (before 37 weeks). Arterial involvement (17/21) was predominant, of which stroke (12/17) was the most prevalent clinical manifestation. Anti-cardiolipin antibodies were predominant (13/21) in the antiphospholipid antibody profiles. Treatments were based on the use of symptomatics such as antiepileptics (8/21), and 6/21 patients received heparin. There were 4 deaths (4/21); otherwise, the children recovered well, especially the neonates who suffered from strokes (9/12). CONCLUSION: Neonatal thrombosis and antiphospholipid antibodies are rare. The development of thrombotic manifestations in neonates seems not to be associated exclusively with the aPL, but their etiology may be linked to pre- and perinatal events. We noted good therapeutic responses, especially in stroke patients, who presented with favorable outcomes in 82% of the cases. PMID- 25133198 TI - Uncomplicated diverticular disease: innate and adaptive immunity in human gut mucosa before and after rifaximin. AB - BACKGROUND/AIM: Uncomplicated diverticular disease (UDD) is a frequent condition in adults. The pathogenesis of symptoms remains unknown. Bacteria are able to interact with Toll-like receptors (TLRs) and to induce inflammation through both innate immunity and T-cell recruitment. We investigated the pattern of TLRs 2 and 4 and the intestinal homing in patients with UDD before and after a course of Rifaximin. METHODS: Forty consecutive patients with UDD and 20 healthy asymptomatic subjects were enrolled. Among UDD patients, 20 were assigned to a 2 month course of treatment with Rifaximin 1.2 g/day for 15 days/month and 20 received placebo. Blood sample and colonic biopsies were obtained from patients and controls. The samples were collected and analyzed at baseline and at the end of treatment. Flow cytometry was performed using monoclonal antibodies (CD3, CD4, CD8, CD103, TCR-gamma/delta, CD14, TLR2, and TLR4). RESULTS: In UDD, TLR2 and TLR4 expression on immune cell subpopulations from blood and mucosa of the affected colon are altered as compared with controls. Rifaximin treatment induced significant modifications of altered conditions. CONCLUSIONS: Our data show the role of TLRs in the development of inflammation in UDD. TLRs distribution is altered in UDD and these alterations are reversed after antibiotic treatment. This trial is registered with ClinicalTrials.gov: NCT02068482. PMID- 25133199 TI - SOCS1 and regulation of regulatory T cells plasticity. AB - Several reports have suggested that natural regulatory T cells (Tregs) lose Forkhead box P3 (Foxp3) expression and suppression activity under certain inflammatory conditions. Treg plasticity has been studied because it may be associated with the pathogenesis of autoimmunity. Some studies showed that a minor uncommitted Foxp3(+) T cell population, which lacks hypomethylation at Treg specific demethylation regions (TSDRs), may convert to effector/helper T cells. Suppressor of cytokine signaling 1 (SOCS1), a negative regulator of cytokine signaling, has been reported to play an important role in Treg cell integrity and function by protecting the cells from excessive inflammatory cytokines. In this review, we discuss Treg plasticity and maintenance of suppression functions in both physiological and pathological settings. In addition, we discuss molecular mechanisms of maintaining Treg plasticity by SOCS1 and other molecules. Such information will be useful for therapy of autoimmune diseases and reinforcement of antitumor immunity. PMID- 25133200 TI - Optical imaging in an Alzheimer's mouse model reveals amyloid-beta-dependent vascular impairment. AB - Alzheimer's disease (AD) and cerebrovascular disease are often comorbid conditions, but the relationship between amyloid-beta and in vivo vascular pathophysiology is poorly understood. We utilized a multimodal, multiscale optical imaging approach, including spatial frequency domain imaging, Doppler optical coherence tomography, and confocal microscopy, to quantify AD-dependent changes in a triple transgenic mouse model (3xTg-AD) and age-matched controls. From three months of age (naive) to 20 months (severe AD), the brain tissue concentration of total and oxy-hemoglobin (Total Hb, ctO2Hb) decreased 50 and 70%, respectively, in 3xTg-AD mice. Compared to age-matched controls, significant differences in brain hemoglobin concentrations occurred as early as eight months (Total Hb: 126 +/- 5 MUM versus 108 +/- 4 MUM; ctO2Hb: 86 +/- 5 MUM versus 70 +/- 3 MUM; for control and AD, respectively). These changes were linked to a 29% vascular volume fraction decrease and 35% vessel density reduction in the 20 month-old 3xTg-AD versus age-matched controls. Vascular reduction coincided with increased brain concentration of amyloid-beta protein, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) at eight and 20 months compared to the three-month baseline. Our results suggest that amyloid beta blocks the normally reparative effects of upregulated VEGF and eNOS, and may accelerate in vivo vascular pathophysiology in AD. PMID- 25133202 TI - Malware analysis using visualized image matrices. AB - This paper proposes a novel malware visual analysis method that contains not only a visualization method to convert binary files into images, but also a similarity calculation method between these images. The proposed method generates RGB colored pixels on image matrices using the opcode sequences extracted from malware samples and calculates the similarities for the image matrices. Particularly, our proposed methods are available for packed malware samples by applying them to the execution traces extracted through dynamic analysis. When the images are generated, we can reduce the overheads by extracting the opcode sequences only from the blocks that include the instructions related to staple behaviors such as functions and application programming interface (API) calls. In addition, we propose a technique that generates a representative image for each malware family in order to reduce the number of comparisons for the classification of unknown samples and the colored pixel information in the image matrices is used to calculate the similarities between the images. Our experimental results show that the image matrices of malware can effectively be used to classify malware families both statically and dynamically with accuracy of 0.9896 and 0.9732, respectively. PMID- 25133203 TI - Bird diversity and distribution in relation to urban landscape types in northern Rwanda. AB - Using the point count method, linear mixed models, Shannon's diversity index, and Bray-Curtis cluster analysis, we conducted a study of the effect of urban fabric layout on bird diversity and distribution in northern Rwanda. The results showed a significant effect of city landscapes on bird richness and relative abundance; residential neighborhoods, institutional grounds, and informal settlements had the highest species diversity in comparison to other microlandscape types. Riversides were characterized by specialized bird species, commonly known to be restricted to wetland environments. Built-up areas and open field landscapes had comparable results. One Albertine Rift endemic bird species, the Ruwenzori Double collared Sunbird (Cinnyris stuhlmanni), was recorded. Three migratory birds were found in Musanze city for the first time: the Common Sandpiper (Actitis hypoleucos), the Spotted Flycatcher (Muscicapa striata), and the Willow Warbler (Phylloscopus trochilus). Two bird species have not been previously reported in Rwanda: the Garden Warbler (Sylvia borin) and the Lesser Spotted Eagle (Aquila pomarina). The implications of this study are particularly relevant to urban decision makers who should consider the existence of a great diversity of avian fauna when developing and implementing master plans, especially when villages and cities are in proximity of protected areas or natural reserves. PMID- 25133201 TI - TRANSCRIPTION FACTOR GLI-SIMILAR 3 (GLIS3): IMPLICATIONS FOR THE DEVELOPMENT OF CONGENITAL HYPOTHYROIDISM. AB - Congenital hypothyroidism (CH) is the most frequent endocrine disorder in neonates. While several genetic mutations have been identified that result in developmental defects of the thyroid gland or thyroid hormone synthesis, genetic factors have yet to be identified in many CH patients along with the mechanisms underlying their pathophysiology. Mutations in the gene encoding the Kruppel-like transcription factor, GLI-similar 3 (GLIS3) have been associated with the development of a syndrome characterized by congenital hypothyroidism and neonatal diabetes and similar phenotypes were observed in mouse knockout models of Glis3. Patients with GLIS3-mediated CH exhibit diminished serum levels of thyroxine (T4) and triiodothyronine (T3) and elevated thyroid stimulating hormone (TSH) and thyroglobulin (TG). However, the inconsistent presentation of clinical features associated with this CH has made it difficult to ascertain a causative mechanism. Future elucidation of the biological functions of GLIS3 in the thyroid will be crucial to the discovery of new therapeutic opportunities for the treatment of CH. PMID- 25133204 TI - A community-based walk-in screening of depression in Taiwan. AB - Depression is a crucial public health problem because of its relatively high association with suicidal attempts, prolonged social isolation, poor physical health, and dementia. However, the available data and study on the prevalence of depression in Taiwan were mostly completed within the previous 1 to 2 decades, and these studies were limited to certain areas or populations. Little is known regarding the current status of depression in Taiwan. We used a brief tool, the Center for Epidemiological Studies Depression Scale (CES-D), to screen depression in 4 areas among the general and aged population. The results showed a higher CES D score in the southern area among general (mean +/- SD: 7.8 +/- 8.4) or aged participants (mean +/- SD: 7.2 +/- 8.0) compared with other areas. The ratio of suspected depression patients was 16.4% of all recruited participants and 13.3% of aged participants. These results may provide information for this public health issue. PMID- 25133206 TI - A sequential optimization sampling method for metamodels with radial basis functions. AB - Metamodels have been widely used in engineering design to facilitate analysis and optimization of complex systems that involve computationally expensive simulation programs. The accuracy of metamodels is strongly affected by the sampling methods. In this paper, a new sequential optimization sampling method is proposed. Based on the new sampling method, metamodels can be constructed repeatedly through the addition of sampling points, namely, extrema points of metamodels and minimum points of density function. Afterwards, the more accurate metamodels would be constructed by the procedure above. The validity and effectiveness of proposed sampling method are examined by studying typical numerical examples. PMID- 25133207 TI - Vague congruences and quotient lattice implication algebras. AB - The aim of this paper is to further develop the congruence theory on lattice implication algebras. Firstly, we introduce the notions of vague similarity relations based on vague relations and vague congruence relations. Secondly, the equivalent characterizations of vague congruence relations are investigated. Thirdly, the relation between the set of vague filters and the set of vague congruences is studied. Finally, we construct a new lattice implication algebra induced by a vague congruence, and the homomorphism theorem is given. PMID- 25133208 TI - Utilizing optical coherence tomography in the nondestructive and noncontact measurement of egg shell thickness. AB - The goal of this study was to measure the thickness of egg shells without any contact and by utilizing a nondestructive method that sends infrared light beam on the egg. We obtain measurement resolutions on the order of 7 MUm up to a penetration depth of 1.7 mm from the actual surface of the egg shell. The measurement results we obtained show that optical coherence tomography can be used to accurately determine the egg shell thickness. Scanning the light beam over the surface allows for measuring the egg profile and monitoring the variations of shell thickness. Since this information gives a quantitative value for the uniformity of the egg shell structure, we anticipate that optical coherence tomography may be used in the quantitative evaluation of egg quality in in-line automated inspection systems. PMID- 25133205 TI - Plasminogen activator inhibitor-1 regulates LPS induced inflammation in rat macrophages through autophagy activation. AB - BACKGROUND: The mechanisms by which plasminogen activator inhibitor-1 (PAI-1) regulates inflammation, especially in acute respiratory distress syndrome (ARDS), are largely unknown. OBJECTIVE: To assess the relationship between PAI-1 and autophagy in inflammatory reactions induced by LPS in rat NR8383 cells. METHODS: ELISA was used to assess the amounts of TNF-alpha, IL-1beta, and PAI-1 in cell culture supernatants; TLR4, MyD88, PAI-1, LC3, Beclin1, and mTOR protein and mRNA levels were determined by western blot and quantitative RT-PCR, respectively; western blot was used to determine NF-kappaB protein levels. To further evaluate the role of PAI-1, the PAI-1 gene was downregulated and overexpressed using the siRNA transfection technology and the pCDH-PAI-1, respectively. Finally, the GFP Positive Expression Rate Method was used to determine the rate of GFP-LC3 positive NR8383 cells. RESULTS: In LPS-induced NR8383 cells, TNF-alpha, IL-1beta, and PAI-1 expression levels increased remarkably. Upon PAI-1 knockdown, TNF alpha, IL-1beta, PAI-1, TLR4, MyD88, NF-kappaB, LC3, and Beclin1 levels were decreased, while mTOR increased. Conversely, overexpression of PAI-1 resulted in increased amounts of TNF-alpha, IL-1beta, PAI-1, TLR4, MyD88, NF-kappaB, LC3, and Beclin1. However, no significant change was observed in mTOR expression. CONCLUSIONS: In NR8383 cells, PAI-1 contributes in the regulation of LPS-induced inflammation, likely by promoting autophagy. PMID- 25133209 TI - Modeling the propagation of mobile phone virus under complex network. AB - Mobile phone virus is a rogue program written to propagate from one phone to another, which can take control of a mobile device by exploiting its vulnerabilities. In this paper the propagation model of mobile phone virus is tackled to understand how particular factors can affect its propagation and design effective containment strategies to suppress mobile phone virus. Two different propagation models of mobile phone viruses under the complex network are proposed in this paper. One is intended to describe the propagation of user tricking virus, and the other is to describe the propagation of the vulnerability exploiting virus. Based on the traditional epidemic models, the characteristics of mobile phone viruses and the network topology structure are incorporated into our models. A detailed analysis is conducted to analyze the propagation models. Through analysis, the stable infection-free equilibrium point and the stability condition are derived. Finally, considering the network topology, the numerical and simulation experiments are carried out. Results indicate that both models are correct and suitable for describing the spread of two different mobile phone viruses, respectively. PMID- 25133210 TI - Features extraction of flotation froth images and BP neural network soft-sensor model of concentrate grade optimized by shuffled cuckoo searching algorithm. AB - For meeting the forecasting target of key technology indicators in the flotation process, a BP neural network soft-sensor model based on features extraction of flotation froth images and optimized by shuffled cuckoo search algorithm is proposed. Based on the digital image processing technique, the color features in HSI color space, the visual features based on the gray level cooccurrence matrix, and the shape characteristics based on the geometric theory of flotation froth images are extracted, respectively, as the input variables of the proposed soft sensor model. Then the isometric mapping method is used to reduce the input dimension, the network size, and learning time of BP neural network. Finally, a shuffled cuckoo search algorithm is adopted to optimize the BP neural network soft-sensor model. Simulation results show that the model has better generalization results and prediction accuracy. PMID- 25133212 TI - A mobile anchor assisted localization algorithm based on regular hexagon in wireless sensor networks. AB - Localization is one of the key technologies in wireless sensor networks (WSNs), since it provides fundamental support for many location-aware protocols and applications. Constraints of cost and power consumption make it infeasible to equip each sensor node in the network with a global position system (GPS) unit, especially for large-scale WSNs. A promising method to localize unknown nodes is to use several mobile anchors which are equipped with GPS units moving among unknown nodes and periodically broadcasting their current locations to help nearby unknown nodes with localization. This paper proposes a mobile anchor assisted localization algorithm based on regular hexagon (MAALRH) in two dimensional WSNs, which can cover the whole monitoring area with a boundary compensation method. Unknown nodes calculate their positions by using trilateration. We compare the MAALRH with HILBERT, CIRCLES, and S-CURVES algorithms in terms of localization ratio, localization accuracy, and path length. Simulations show that the MAALRH can achieve high localization ratio and localization accuracy when the communication range is not smaller than the trajectory resolution. PMID- 25133211 TI - Detoxification of corncob acid hydrolysate with SAA pretreatment and xylitol production by immobilized Candida tropicalis. AB - Xylitol fermentation production from corncob acid hydrolysate has become an attractive and promising process. However, corncob acid hydrolysate cannot be directly used as fermentation substrate owing to various inhibitors. In this work, soaking in aqueous ammonia (SAA) pretreatment was employed to reduce the inhibitors in acid hydrolysate. After detoxification, the corncob acid hydrolysate was fermented by immobilized Candida tropicalis cell to produce xylitol. Results revealed that SAA pretreatment showed high delignification and efficient removal of acetyl group compounds without effect on cellulose and xylan content. Acetic acid was completely removed, and the content of phenolic compounds was reduced by 80%. Furthermore, kinetic behaviors of xylitol production by immobilized C. tropicalis cell were elucidated from corncob acid hydrolysate detoxified with SAA pretreatment and two-step adsorption method, respectively. The immobilized C. tropicalis cell showed higher productivity efficiency using the corncob acid hydrolysate as fermentation substrate after detoxification with SAA pretreatment than by two-step adsorption method in the five successive batch fermentation rounds. After the fifth round fermentation, about 60 g xylitol/L fermentation substrate was obtained for SAA pretreatment detoxification, while about 30 g xylitol/L fermentation substrate was obtained for two-step adsorption detoxification. PMID- 25133213 TI - Hydraulic transients in the long diversion-type hydropower station with a complex differential surge tank. AB - Based on the theory of hydraulic transients and the method of characteristics (MOC), a mathematic model of the differential surge tank with pressure-reduction orifices (PROs) and overflow weirs for transient calculation is proposed. The numerical model of hydraulic transients is established using the data of a practical hydropower station; and the probable transients are simulated. The results show that successive load rejection is critical for calculating the maximum pressure in spiral case and the maximum rotating speed of runner when the bifurcated pipe is converging under the surge tank in a diversion-type hydropower station; the pressure difference between two sides of breast wall is large during transient conditions, and it would be more serious when simultaneous load rejections happen after load acceptance; the reasonable arrangement of PROs on breast wall can effectively decrease the pressure difference. PMID- 25133214 TI - A novel user classification method for femtocell network by using affinity propagation algorithm and artificial neural network. AB - An artificial neural network (ANN) and affinity propagation (AP) algorithm based user categorization technique is presented. The proposed algorithm is designed for closed access femtocell network. ANN is used for user classification process and AP algorithm is used to optimize the ANN training process. AP selects the best possible training samples for faster ANN training cycle. The users are distinguished by using the difference of received signal strength in a multielement femtocell device. A previously developed directive microstrip antenna is used to configure the femtocell device. Simulation results show that, for a particular house pattern, the categorization technique without AP algorithm takes 5 indoor users and 10 outdoor users to attain an error-free operation. While integrating AP algorithm with ANN, the system takes 60% less training samples reducing the training time up to 50%. This procedure makes the femtocell more effective for closed access operation. PMID- 25133215 TI - A parametric study of nonlinear seismic response analysis of transmission line structures. AB - A parametric study of nonlinear seismic response analysis of transmission line structures subjected to earthquake loading is studied in this paper. The transmission lines are modeled by cable element which accounts for the nonlinearity of the cable based on a real project. Nonuniform ground motions are generated using a stochastic approach based on random vibration analysis. The effects of multicomponent ground motions, correlations among multicomponent ground motions, wave travel, coherency loss, and local site on the responses of the cables are investigated using nonlinear time history analysis method, respectively. The results show the multicomponent seismic excitations should be considered, but the correlations among multicomponent ground motions could be neglected. The wave passage effect has a significant influence on the responses of the cables. The change of the degree of coherency loss has little influence on the response of the cables, but the responses of the cables are affected significantly by the effect of coherency loss. The responses of the cables change little with the degree of the difference of site condition changing. The effect of multicomponent ground motions, wave passage, coherency loss, and local site should be considered for the seismic design of the transmission line structures. PMID- 25133216 TI - Effects of soil temperature, flooding, and organic matter addition on N2O emissions from a soil of Hongze Lake wetland, China. AB - The objectives of this study were to test the effects of soil temperature, flooding, and raw organic matter input on N2O emissions in a soil sampled at Hongze Lake wetland, Jiangsu Province, China. The treatments studied were-peat soil (I), peat soil under flooding (II), peat soil plus raw organic matter (III), and peat soil under flooding plus organic matter. These four treatments were incubated at 20 degrees C and 35 degrees C. The result showed that temperature increase could enhance N2O emissions rate and cumulative emissions significantly; moreover, the flooded soil with external organic matter inputs showed the lowest cumulative rise in N2O emissions due to temperature increment. Flooding might inhibit soil N2O emissions, and the inhibition was more pronounced after organic matter addition to the original soil. Conversely, organic matter input explained lower cumulative N2O emissions under flooding. Our results suggest that complex interactions between flooding and other environmental factors might appear in soil N2O emissions. Further studies are needed to understand potential synergies or antagonisms between environmental factors that control N2O emissions in wetland soils. PMID- 25133218 TI - Flavonoids in Juglans regia L. leaves and evaluation of in vitro antioxidant activity via intracellular and chemical methods. AB - Flavonoids are rich in Juglans regia L. leaves. They have potent antioxidant properties, which have been related to regulating immune function and enhancing anticancer activity. Herein, qualitative and quantitative determination of flavonoids from J. regia leaves was carried out using high performance liquid chromatography coupled with tandem mass spectrometry with electrospray ionization and negative ion detection (HPLC-ESI-MS/MS) by comparison of the retention times and mass spectral fragments with standard substances or related literatures. Seventeen compounds were identified and major components are quercetin-3-O rhamnoside (453.11 MUg/g, dry weight), quercetin-3-O-arabinoside (73.91 MUg/g), quercetin-3-O-xyloside (70.04 MUg/g), kaempferol-O-pentoside derivative (49.04 MUg/g), quercetin-3-O-galactoside (48.61 MUg/g), and kaempferol-O-pentoside (48.46 MUg/g). The in vitro intracellular antioxidation indicated that flavonoids from J. regia leaves could reduce the reactive oxygen species (ROS) level in RAW264.7 cells and showed good radical scavenging activities. These results proved to be more related to the flavonoids that could be considered in the design of new formulations of dietary supplements or functional foods. PMID- 25133219 TI - Multicriteria group decision making by using trapezoidal valued hesitant fuzzy sets. AB - The concept of trapezoidal valued hesitant fuzzy set is introduced. Notion for distance between any two trapezoidal valued hesitant fuzzy elements is given. Using this proposed distance measure, we extend the technique for order preference by similarity to ideal solution for trapezoidal valued hesitant fuzzy sets. An example is constructed to show usefulness of this extension for multicriteria group decision making, where the opinions about the criteria values are expressed as trapezoidal valued hesitant fuzzy set. PMID- 25133217 TI - Comparison of clinical safety and outcomes of early versus delayed laparoscopic cholecystectomy for acute cholecystitis: a meta-analysis. AB - OBJECTIVE: To compare the clinical safety and outcomes of early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy for acute cholecystitis. METHODS: Pertinent studies were selected from the Medline, EMBASE, and Cochrane library databases, references from published articles, and reviews. Seven randomized controlled trials (early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy) were selected. Conventional meta-analysis according to Cochrane Collaboration was used for the pooling of the results. RESULTS: Seven trials with 1106 patients were included. There was no significant difference between the two groups in terms of bile duct injury (Peto odds ratio 0.49 (95% confidence interval 0.05 to 4.72); P = 0.54) or conversion to open cholecystectomy (risk ratio 0.91 (95% confidence interval 0.69 to 1.20); P = 0.50). The total hospital stay was shorter by 4 days for early laparoscopic cholecystectomy (mean difference -4.12 (95% confidence interval -5.22 to -3.03) days; P < 0.00001). CONCLUSION: Early laparoscopic cholecystectomy during acute cholecystitis is safe and shortens the total hospital stay. PMID- 25133220 TI - New ray tracing method to investigate the various effects on wave propagation in medical scenario: an application of wireless body area network. AB - The advent of technology with the increasing use of wireless network has led to the development of Wireless Body Area Network (WBAN) to continuously monitor the change of physiological data in a cost efficient manner. As numerous researches on wave propagation characterization have been done in intrabody communication, this study has given emphasis on the wave propagation characterization between the control units (CUs) and wireless access point (AP) in a hospital scenario. Ray tracing is a tool to predict the rays to characterize the wave propagation. It takes huge simulation time, especially when multiple transmitters are involved to transmit physiological data in a realistic hospital environment. Therefore, this study has developed an accelerated ray tracing method based on the nearest neighbor cell and prior knowledge of intersection techniques. Beside this, Red Black tree is used to store and provide a faster retrieval mechanism of objects in the hospital environment. To prove the superiority, detailed complexity analysis and calculations of reflection and transmission coefficients are also presented in this paper. The results show that the proposed method is about 1.51, 2.1, and 2.9 times faster than the Object Distribution Technique (ODT), Space Volumetric Partitioning (SVP), and Angular Z-Buffer (AZB) methods, respectively. To show the various effects on received power in 60 GHz frequency, few comparisons are made and it is found that on average -9.44 dBm, -8.23 dBm, and 9.27 dBm received power attenuations should be considered when human, AP, and CU move in a given hospital scenario. PMID- 25133221 TI - Prediction of the reference evapotranspiration using a chaotic approach. AB - Evapotranspiration is one of the most important hydrological variables in the context of water resources management. An attempt was made to understand and predict the dynamics of reference evapotranspiration from a nonlinear dynamical perspective in this study. The reference evapotranspiration data was calculated using the FAO Penman-Monteith equation with the observed daily meteorological data for the period 1966-2005 at four meteorological stations (i.e., Baotou, Zhangbei, Kaifeng, and Shaoguan) representing a wide range of climatic conditions of China. The correlation dimension method was employed to investigate the chaotic behavior of the reference evapotranspiration series. The existence of chaos in the reference evapotranspiration series at the four different locations was proved by the finite and low correlation dimension. A local approximation approach was employed to forecast the daily reference evapotranspiration series. Low root mean square error (RSME) and mean absolute error (MAE) (for all locations lower than 0.31 and 0.24, resp.), high correlation coefficient (CC), and modified coefficient of efficiency (for all locations larger than 0.97 and 0.8, resp.) indicate that the predicted reference evapotranspiration agrees well with the observed one. The encouraging results indicate the suitableness of chaotic approach for understanding and predicting the dynamics of the reference evapotranspiration. PMID- 25133222 TI - Node deployment algorithm based on viscous fluid model for wireless sensor networks. AB - With the scale expands, traditional deployment algorithms are becoming increasingly complicated than before, which are no longer fit for sensor networks. In order to reduce the complexity, we propose a node deployment algorithm based on viscous fluid model. In wireless sensor networks, sensor nodes are abstracted as fluid particles. Similar to the diffusion and self-propagation behavior of fluid particles, sensor nodes realize deployment in unknown region following the motion rules of fluid. Simulation results show that our algorithm archives good coverage rate and homogeneity in large-scale sensor networks. PMID- 25133223 TI - Investigation of antioxidant and hepatoprotective activity of standardized Curcuma xanthorrhiza rhizome in carbon tetrachloride-induced hepatic damaged rats. AB - Curcuma xanthorrhiza (CX) has been used for centuries in traditional system of medicine to treat several diseases such as hepatitis, liver complaints, and diabetes. It has been consumed as food supplement and "jamu" as a remedy for hepatitis. Hence, CX was further explored for its potential as a functional food for liver related diseases. As such, initiative was taken to evaluate the antioxidant and hepatoprotective potential of CX rhizome. Antioxidant activity of the standardized CX fractions was determined using in vitro assays. Hepatoprotective assay was conducted against carbon tetrachloride- (CCl4-) induced hepatic damage in rats at doses of 125, 250, and 500 mg/kg of hexane fraction. Highest antioxidant activity was found in hexane fraction. In the case of hepatoprotective activity, CX hexane fraction showed significant improvement in terms of a biochemical liver function, antioxidative liver enzymes, and lipid peroxidation activity. Good recovery was observed in the treated hepatic tissues histologically. Hence, the results concluded that CX hexane fraction possessed prominent hepatoprotective activities which might be due to its in vitro antioxidant activity. These findings also support the use of CX as a functional food for hepatitis remedy in traditional medicinal system. PMID- 25133224 TI - Reliable multihop broadcast protocol with a low-overhead link quality assessment for ITS based on VANETs in highway scenarios. AB - Vehicular ad hoc networks (VANETs) have been identified as a key technology to enable intelligent transport systems (ITS), which are aimed to radically improve the safety, comfort, and greenness of the vehicles in the road. However, in order to fully exploit VANETs potential, several issues must be addressed. Because of the high dynamic of VANETs and the impairments in the wireless channel, one key issue arising when working with VANETs is the multihop dissemination of broadcast packets for safety and infotainment applications. In this paper a reliable low overhead multihop broadcast (RLMB) protocol is proposed to address the well-known broadcast storm problem. The proposed RLMB takes advantage of the hello messages exchanged between the vehicles and it processes such information to intelligently select a relay set and reduce the redundant broadcast. Additionally, to reduce the hello messages rate dependency, RLMB uses a point-to-zone link evaluation approach. RLMB performance is compared with one of the leading multihop broadcast protocols existing to date. Performance metrics show that our RLMB solution outperforms the leading protocol in terms of important metrics such as packet dissemination ratio, overhead, and delay. PMID- 25133225 TI - A memristive hyperchaotic system without equilibrium. AB - A new memristive system is presented in this paper. The peculiarity of the model is that it does not display any equilibria and exhibits periodic, chaotic, and also hyperchaotic dynamics in a particular range of the parameters space. The behavior of the proposed system is investigated through numerical simulations, such as phase portraits, Lyapunov exponents, and Poincare sections, and circuital implementation confirmed the hyperchaotic dynamic. PMID- 25133226 TI - Some gastrointestinal tract characteristics of Karayaka ram lambs slaughtered at different weights. AB - Thirty-one Karayaka ram lambs were slaughtered at different body weights (30 (n = 7), 35 (n = 6), 40 (n = 7), 45 (n = 6), and 50 (n = 5) kg of body weight at fast) to evaluate the growth of their gastrointestinal tract (GIT) characteristics, to determine the relationship among slaughter body weight (SBW) and empty body weight (EBW), whole GIT and segments, and the influence of slaughter weight on the pH of rumen, jejunum, and cecal contents. The effects of the SBW on GIT weight (P < 0.05), stomach (P < 0.001), and intestine (P < 0.05), the body length (P < 0.001) and caecum (P < 0.05), and the relative weights of GIT (P < 0.05), stomach (P < 0.001), and intestine (P < 0.001) were linear whereas that for the length of intestine were quadratic. The effect of SBW were quadratic (P < 0.05) on ratios of stomach to GIT weight and intestine length to intestine weight and rumen pH while, for the intestine to GIT weight ratio (P < 0.001) and caecum pH (P < 0.05), this effect was linear. The results indicated that for all parameters studied, with the exception of intestinal length and cecal pH, linear relationships were observed with SBW indicating steady growth rates for these tissues. PMID- 25133227 TI - Online handwritten signature verification using neural network classifier based on principal component analysis. AB - One of the main difficulties in designing online signature verification (OSV) system is to find the most distinctive features with high discriminating capabilities for the verification, particularly, with regard to the high variability which is inherent in genuine handwritten signatures, coupled with the possibility of skilled forgeries having close resemblance to the original counterparts. In this paper, we proposed a systematic approach to online signature verification through the use of multilayer perceptron (MLP) on a subset of principal component analysis (PCA) features. The proposed approach illustrates a feature selection technique on the usually discarded information from PCA computation, which can be significant in attaining reduced error rates. The experiment is performed using 4000 signature samples from SIGMA database, which yielded a false acceptance rate (FAR) of 7.4% and a false rejection rate (FRR) of 6.4%. PMID- 25133228 TI - Part-based visual tracking via online weighted P-N learning. AB - We propose a novel part-based tracking algorithm using online weighted P-N learning. An online weighted P-N learning method is implemented via considering the weight of samples during classification, which improves the performance of classifier. We apply weighted P-N learning to track a part-based target model instead of whole target. In doing so, object is segmented into fragments and parts of them are selected as local feature blocks (LFBs). Then, the weighted P-N learning is employed to train classifier for each local feature block (LFB). Each LFB is tracked through the corresponding classifier, respectively. According to the tracking results of LFBs, object can be then located. During tracking process, to solve the issues of occlusion or pose change, we use a substitute strategy to dynamically update the set of LFB, which makes our tracker robust. Experimental results demonstrate that the proposed method outperforms the state of-the-art trackers. PMID- 25133229 TI - Greenhouse gas emissions from cotton field under different irrigation methods and fertilization regimes in arid northwestern China. AB - Drip irrigation is broadly extended in order to save water in the arid cotton production region of China. Biochar is thought to be a useful soil amendment to reduce greenhouse gas (GHG) emissions. Here, a field study was conducted to compare the emissions of nitrous oxide (N2O) and methane (CH4) under different irrigation methods (drip irrigation (D) and furrow irrigation (F)) and fertilization regimes (conventional fertilization (C) and conventional fertilization + biochar (B)) during the cotton growth season. The accumulated N2O emissions were significantly lower with FB, DC, and DB than with FC by 28.8%, 36.1%, and 37.6%, while accumulated CH4 uptake was 264.5%, 226.7%, and 154.2% higher with DC, DB, and FC than that with FB, respectively. Irrigation methods showed a significant effect on total global warming potential (GWP) and yield scaled GWP (P < 0.01). DC and DB showed higher cotton yield, water use efficiency (WUE), and lower yield-scaled GWP, as compared with FC and FB. This suggests that in northwestern China mulched-drip irrigation should be a better approach to increase cotton yield with depressed GHG. In addition, biochar addition increased CH4 emissions while it decreased N2O emissions. PMID- 25133230 TI - Simple BiCMOS CCCTA design and resistorless analog function realization. AB - The simple realization of the current-controlled conveyor transconductance amplifier (CCCTA) in BiCMOS technology is introduced. The proposed BiCMOS CCCTA realization is based on the use of differential pair and basic current mirror, which results in simple structure. Its characteristics, that is, parasitic resistance (R x) and current transfer (i o/i z), are also tunable electronically by external bias currents. The realized circuit is suitable for fabrication using standard 0.35 MUm BiCMOS technology. Some simple and compact resistorless applications employing the proposed CCCTA as active elements are also suggested, which show that their circuit characteristics with electronic controllability are obtained. PSPICE simulation results demonstrating the circuit behaviors and confirming the theoretical analysis are performed. PMID- 25133231 TI - Cyclic soft groups and their applications on groups. AB - In crisp environment the notions of order of group and cyclic group are well known due to many applications. In this paper, we introduce order of the soft groups, power of the soft sets, power of the soft groups, and cyclic soft group on a group. We also investigate the relationship between cyclic soft groups and classical groups. PMID- 25133232 TI - An efficient approach to obtain optimal load factors for structural design. AB - An efficient optimization approach is described to calibrate load factors used for designing of structures. The load factors are calibrated so that the structural reliability index is as close as possible to a target reliability value. The optimization procedure is applied to find optimal load factors for designing of structures in accordance with the new version of the Mexico City Building Code (RCDF). For this aim, the combination of factors corresponding to dead load plus live load is considered. The optimal combination is based on a parametric numerical analysis of several reinforced concrete elements, which are designed using different load factor values. The Monte Carlo simulation technique is used. The formulation is applied to different failure modes: flexure, shear, torsion, and compression plus bending of short and slender reinforced concrete elements. Finally, the structural reliability corresponding to the optimal load combination proposed here is compared with that corresponding to the load combination recommended by the current Mexico City Building Code. PMID- 25133233 TI - Effect of temperature shock and inventory surprises on natural gas and heating oil futures returns. AB - The aim of this paper is to examine the impact of temperature shock on both near month and far-month natural gas and heating oil futures returns by extending the weather and storage models of the previous study. Several notable findings from the empirical studies are presented. First, the expected temperature shock significantly and positively affects both the near-month and far-month natural gas and heating oil futures returns. Next, significant temperature shock has effect on both the conditional mean and volatility of natural gas and heating oil prices. The results indicate that expected inventory surprises significantly and negatively affects the far-month natural gas futures returns. Moreover, volatility of natural gas futures returns is higher on Thursdays and that of near month heating oil futures returns is higher on Wednesdays than other days. Finally, it is found that storage announcement for natural gas significantly affects near-month and far-month natural gas futures returns. Furthermore, both natural gas and heating oil futures returns are affected more by the weighted average temperature reported by multiple weather reporting stations than that reported by a single weather reporting station. PMID- 25133235 TI - Event-based user classification in Weibo media. AB - Weibo media, known as the real-time microblogging services, has attracted massive attention and support from social network users. Weibo platform offers an opportunity for people to access information and changes the way people acquire and disseminate information significantly. Meanwhile, it enables people to respond to the social events in a more convenient way. Much of the information in Weibo media is related to some events. Users who post different contents, and exert different behavior or attitude may lead to different contribution to the specific event. Therefore, classifying the large amount of uncategorized social circles generated in Weibo media automatically from the perspective of events has been a promising task. Under this circumstance, in order to effectively organize and manage the huge amounts of users, thereby further managing their contents, we address the task of user classification in a more granular, event-based approach in this paper. By analyzing real data collected from Sina Weibo, we investigate the Weibo properties and utilize both content information and social network information to classify the numerous users into four primary groups: celebrities, organizations/media accounts, grassroots stars, and ordinary individuals. The experiments results show that our method identifies the user categories accurately. PMID- 25133234 TI - Protein binding site prediction by combining hidden Markov support vector machine and profile-based propensities. AB - Identification of protein binding sites is critical for studying the function of the proteins. In this paper, we proposed a method for protein binding site prediction, which combined the order profile propensities and hidden Markov support vector machine (HM-SVM). This method employed the sequential labeling technique to the field of protein binding site prediction. The input features of HM-SVM include the profile-based propensities, the Position-Specific Score Matrix (PSSM), and Accessible Surface Area (ASA). When tested on different data sets, the proposed method showed promising results, and outperformed some closely relative methods by more than 10% in terms of AUC. PMID- 25133236 TI - Fuzzy-based trust prediction model for routing in WSNs. AB - The cooperative nature of multihop wireless sensor networks (WSNs) makes it vulnerable to varied types of attacks. The sensitive application environments and resource constraints of WSNs mandate the requirement of lightweight security scheme. The earlier security solutions were based on historical behavior of neighbor but the security can be enhanced by predicting the future behavior of the nodes in the network. In this paper, we proposed a fuzzy-based trust prediction model for routing (FTPR) in WSNs with minimal overhead in regard to memory and energy consumption. FTPR incorporates a trust prediction model that predicts the future behavior of the neighbor based on the historical behavior, fluctuations in trust value over a period of time, and recommendation inconsistency. In order to reduce the control overhead, FTPR received recommendations from a subset of neighbors who had maximum number of interactions with the requestor. Theoretical analysis and simulation results of FTPR protocol demonstrate higher packet delivery ratio, higher network lifetime, lower end-to end delay, and lower memory and energy consumption than the traditional and existing trust-based routing schemes. PMID- 25133237 TI - Capacitance-based frequency adjustment of micro piezoelectric vibration generator. AB - Micro piezoelectric vibration generator has a wide application in the field of microelectronics. Its natural frequency is unchanged after being manufactured. However, resonance cannot occur when the natural frequencies of a piezoelectric generator and the source of vibration frequency are not consistent. Output voltage of the piezoelectric generator will sharply decline. It cannot normally supply power for electronic devices. In order to make the natural frequency of the generator approach the frequency of vibration source, the capacitance FM technology is adopted in this paper. Different capacitance FM schemes are designed by different locations of the adjustment layer. The corresponding capacitance FM models have been established. Characteristic and effect of the capacitance FM have been simulated by the FM model. Experimental results show that the natural frequency of the generator could vary from 46.5 Hz to 42.4 Hz when the bypass capacitance value increases from 0 nF to 30 nF. The natural frequency of a piezoelectric vibration generator could be continuously adjusted by this method. PMID- 25133238 TI - Functioning of women with migraine headaches. AB - BACKGROUND: Migraines are one of the most commonly occurring ailments affecting the nervous system. The aim of this research paper was to evaluate the effect migraines have on the everyday functioning of women. METHOD: The study involved women with diagnosed migraine headaches (IHS-2004) undergoing treatment at a neurological clinic. In order to evaluate the influence of headaches on the everyday functioning of women, a MSQ v.2 questionnaire was used, whereas pain severity was assessed on a linear VAS scale. RESULTS: Among the clinical factors, the most influential was the frequency of headaches. Headache duration was particularly significant for women below the age of 40. Pain severity cited at 8 10 pts on the VAS significantly disrupted and limited everyday functioning. On the emotional function subscale, the most influential factors were age, education, and the frequency of headaches. CONCLUSIONS: On account of headache frequency emerging as the most significant influencing factor, it is of the utmost importance to inform patients of the value of taking prophylactic measures. Central to this is the identification of factors that trigger the onset of migraines. This approach would greatly aid the individual in choosing the appropriate treatment, either pharmacological or others. PMID- 25133239 TI - Effects of dimethylaminoethanol and compound amino acid on D-galactose induced skin aging model of rat. AB - A lasting dream of human beings is to reverse or postpone aging. In this study, dimethylaminoethanol (DMAE) and compound amino acid (AA) in Mesotherapy were investigated for their potential antiaging effects on D-galactose induced aging skin. At 18 days after D-gal induction, each rat was treated with intradermal microinjection of saline, AA, 0.1% DMAE, 0.2% DMAE, 0.1% DMAE + AA, or 0.2% DMAE + AA, respectively. At 42 days after treatment, the skin wound was harvested and assayed. Measurement of epidermal and dermal thickness in 0.1% DMAE + AA and 0.2% DMAE + AA groups appeared significantly thicker than aging control rats. No differences were found in tissue water content among groups. Hydroxyproline in 0.1% DMAE + AA, 0.2% DMAE + AA, and sham control groups was much higher than all other groups. Collagen type I, type III, and MMP-1 expression was highly upregulated in both 0.1% DMAE + AA and 0.2% DMAE + AA groups compared with aging control. In contrast, TIMP-1 expression levels of various aging groups were significantly reduced when compared to sham control. Coinjection of DMAE and AA into target tissue has marked antiaging effects on D-galactose induced skin aging model of rat. PMID- 25133240 TI - Modelling hydrology of a single bioretention system with HYDRUS-1D. AB - A study was carried out on the effectiveness of bioretention systems to abate stormwater using computer simulation. The hydrologic performance was simulated for two bioretention cells using HYDRUS-1D, and the simulation results were verified by field data of nearly four years. Using the validated model, the optimization of design parameters of rainfall return period, filter media depth and type, and surface area was discussed. And the annual hydrologic performance of bioretention systems was further analyzed under the optimized parameters. The study reveals that bioretention systems with underdrains and impervious boundaries do have some detention capability, while their total water retention capability is extremely limited. Better detention capability is noted for smaller rainfall events, deeper filter media, and design storms with a return period smaller than 2 years, and a cost-effective filter media depth is recommended in bioretention design. Better hydrologic effectiveness is achieved with a higher hydraulic conductivity and ratio of the bioretention surface area to the catchment area, and filter media whose conductivity is between the conductivity of loamy sand and sandy loam, and a surface area of 10% of the catchment area is recommended. In the long-term simulation, both infiltration volume and evapotranspiration are critical for the total rainfall treatment in bioretention systems. PMID- 25133241 TI - A single-phase embedded Z-source DC-AC inverter. AB - In the conventional DC-AC inverter consisting of two DC-DC converters with unipolar output capacitors, the output capacitor voltages of the DC-DC converters must be higher than the DC input voltage. To overcome this weakness, this paper proposes a single-phase DC-AC inverter consisting of two embedded Z-source converters with bipolar output capacitors. The proposed inverter is composed of two embedded Z-source converters with a common DC source and output AC load. Though the output capacitor voltages of the converters are relatively low compared to those of a conventional inverter, an equivalent level of AC output voltages can be obtained. Moreover, by controlling the output capacitor voltages asymmetrically, the AC output voltage of the proposed inverter can be higher than the DC input voltage. To verify the validity of the proposed inverter, experiments were performed with a DC source voltage of 38 V. By controlling the output capacitor voltages of the converters symmetrically or asymmetrically, the proposed inverter can produce sinusoidal AC output voltages. The experiments show that efficiencies of up to 95% and 97% can be achieved with the proposed inverter using symmetric and asymmetric control, respectively. PMID- 25133242 TI - A novel method for functional annotation prediction based on combination of classification methods. AB - Automated protein function prediction defines the designation of functions of unknown protein functions by using computational methods. This technique is useful to automatically assign gene functional annotations for undefined sequences in next generation genome analysis (NGS). NGS is a popular research method since high-throughput technologies such as DNA sequencing and microarrays have created large sets of genes. These huge sequences have greatly increased the need for analysis. Previous research has been based on the similarities of sequences as this is strongly related to the functional homology. However, this study aimed to designate protein functions by automatically predicting the function of the genome by utilizing InterPro (IPR), which can represent the properties of the protein family and groups of the protein function. Moreover, we used gene ontology (GO), which is the controlled vocabulary used to comprehensively describe the protein function. To define the relationship between IPR and GO terms, three pattern recognition techniques have been employed under different conditions, such as feature selection and weighted value, instead of a binary one. PMID- 25133243 TI - A new solution to the matrix equation X - AXB = C. AB - We investigate the matrix equation X - AXB = C. For convenience, the matrix equation X - AXB = C is named as Kalman-Yakubovich-conjugate matrix equation. The explicit solution is constructed when the above matrix equation has unique solution. And this solution is stated as a polynomial of coefficient matrices of the matrix equation. Moreover, the explicit solution is also expressed by the symmetric operator matrix, controllability matrix, and observability matrix. The proposed approach does not require the coefficient matrices to be in arbitrary canonical form. At the end of this paper, the numerical example is shown to illustrate the effectiveness of the proposed method. PMID- 25133244 TI - Effect of zirconium oxide nanofiller and dibutyl phthalate plasticizer on ionic conductivity and optical properties of solid polymer electrolyte. AB - New solid polymer electrolytes (SPE) based on poly(ethylene oxide) (PEO) doped with lithium trifluoromethanesulfonate (LiCF3SO3), dibutyl phthalate (DBP) plasticizer, and zirconium oxide (ZrO2) nanoparticles were prepared by solution casting technique. The conductivity was enhanced by addition of dibutyl phthalate (DBP) plasticizer and ZrO2 nanofiller with maximum conductivity (1.38 * 10(-4) Scm(-1)). The absorption edge and band gap values showed decreases upon addition of LiSO3CF3, DBP, and ZrO2 due to the formation of localized states in the SPE and the degree of disorder in the films increased. PMID- 25133245 TI - Design and realization of a planar ultrawideband antenna with notch band at 3.5 GHz. AB - A small antenna with single notch band at 3.5 GHz is designed for ultrawideband (UWB) communication applications. The fabricated antenna comprises a radiating monopole element and a perfectly conducting ground plane with a wide slot. To achieve a notch band at 3.5 GHz, a parasitic element has been inserted in the same plane of the substrate along with the radiating patch. Experimental results shows that, by properly adjusting the position of the parasitic element, the designed antenna can achieve an ultrawide operating band of 3.04 to 11 GHz with a notched band operating at 3.31-3.84 GHz. Moreover, the proposed antenna achieved a good gain except at the notched band and exhibits symmetric radiation patterns throughout the operating band. The prototype of the proposed antenna possesses a very compact size and uses simple structures to attain the stop band characteristic with an aim to lessen the interference between UWB and worldwide interoperability for microwave access (WiMAX) band. PMID- 25133247 TI - Dynamic finite element analysis of mobile bearing type knee prosthesis under deep flexional motion. AB - The primary objective of this study is to distinguish between mobile bearing and fixed bearing posterior stabilized knee prostheses in the mechanics performance using the finite element simulation. Quantifying the relative mechanics attributes and survivorship between the mobile bearing and the fixed bearing prosthesis remains in investigation among researchers. In the present study, 3 dimensional computational model of a clinically used mobile bearing PS type knee prosthesis was utilized to develop a finite element and dynamic simulation model. Combination of displacement and force driven knee motion was adapted to simulate a flexion motion from 0 degrees to 135 degrees with neutral, 10 degrees , and 20 degrees internal tibial rotation to represent deep knee bending. Introduction of the secondary moving articulation in the mobile bearing knee prosthesis has been found to maintain relatively low shear stress during deep knee motion with tibial rotation. PMID- 25133246 TI - Genome wide analysis of sex difference in gene expression profiles of bone formations using sfx mice and BXD RI strains. AB - The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result indicated that there was a sex difference in the whole genome profiles in sfx mice as measured by the proportion of up- and downregulated genes. Several genes in the pathway of bone development are differentially expressed between the male and female of sfx mice. Comparison of gene network of up- and downregulated bone relevant genes also suggests a sex difference. PMID- 25133248 TI - Automated long-term monitoring of parallel microfluidic operations applying a machine vision-assisted positioning method. AB - As microfluidics has been applied extensively in many cell and biochemical applications, monitoring the related processes is an important requirement. In this work, we design and fabricate a high-throughput microfluidic device which contains 32 microchambers to perform automated parallel microfluidic operations and monitoring on an automated stage of a microscope. Images are captured at multiple spots on the device during the operations for monitoring samples in microchambers in parallel; yet the device positions may vary at different time points throughout operations as the device moves back and forth on a motorized microscopic stage. Here, we report an image-based positioning strategy to realign the chamber position before every recording of microscopic image. We fabricate alignment marks at defined locations next to the chambers in the microfluidic device as reference positions. We also develop image processing algorithms to recognize the chamber positions in real-time, followed by realigning the chambers to their preset positions in the captured images. We perform experiments to validate and characterize the device functionality and the automated realignment operation. Together, this microfluidic realignment strategy can be a platform technology to achieve precise positioning of multiple chambers for general microfluidic applications requiring long-term parallel monitoring of cell and biochemical activities. PMID- 25133249 TI - Investigation of a novel common subexpression elimination method for low power and area efficient DCT architecture. AB - A wide interest has been observed to find a low power and area efficient hardware design of discrete cosine transform (DCT) algorithm. This research work proposed a novel Common Subexpression Elimination (CSE) based pipelined architecture for DCT, aimed at reproducing the cost metrics of power and area while maintaining high speed and accuracy in DCT applications. The proposed design combines the techniques of Canonical Signed Digit (CSD) representation and CSE to implement the multiplier-less method for fixed constant multiplication of DCT coefficients. Furthermore, symmetry in the DCT coefficient matrix is used with CSE to further decrease the number of arithmetic operations. This architecture needs a single port memory to feed the inputs instead of multiport memory, which leads to reduction of the hardware cost and area. From the analysis of experimental results and performance comparisons, it is observed that the proposed scheme uses minimum logic utilizing mere 340 slices and 22 adders. Moreover, this design meets the real time constraints of different video/image coders and peak-signal to-noise-ratio (PSNR) requirements. Furthermore, the proposed technique has significant advantages over recent well-known methods along with accuracy in terms of power reduction, silicon area usage, and maximum operating frequency by 41%, 15%, and 15%, respectively. PMID- 25133250 TI - Structural health monitoring of civil infrastructure using optical fiber sensing technology: a comprehensive review. AB - In the last two decades, a significant number of innovative sensing systems based on optical fiber sensors have been exploited in the engineering community due to their inherent distinctive advantages such as small size, light weight, immunity to electromagnetic interference (EMI) and corrosion, and embedding capability. A lot of optical fiber sensor-based monitoring systems have been developed for continuous measurement and real-time assessment of diversified engineering structures such as bridges, buildings, tunnels, pipelines, wind turbines, railway infrastructure, and geotechnical structures. The purpose of this review article is devoted to presenting a summary of the basic principles of various optical fiber sensors, innovation in sensing and computational methodologies, development of novel optical fiber sensors, and the practical application status of the optical fiber sensing technology in structural health monitoring (SHM) of civil infrastructure. PMID- 25133252 TI - 50 MHz-10 GHz low-power resistive feedback current-reuse mixer with inductive peaking for cognitive radio receiver. AB - A low-power wideband mixer is designed and implemented in 0.13 um standard CMOS technology based on resistive feedback current-reuse (RFCR) configuration for the application of cognitive radio receiver. The proposed RFCR architecture incorporates an inductive peaking technique to compensate for gain roll-off at high frequency while enhancing the bandwidth. A complementary current-reuse technique is used between transconductance and IF stages to boost the conversion gain without additional power consumption by reusing the DC bias current of the LO stage. This downconversion double-balanced mixer exhibits a high and flat conversion gain (CG) of 14.9 +/- 1.4 dB and a noise figure (NF) better than 12.8 dB. The maximum input 1-dB compression point (P1dB) and maximum input third-order intercept point (IIP3) are -13.6 dBm and -4.5 dBm, respectively, over the desired frequency ranging from 50 MHz to 10 GHz. The proposed circuit operates down to a supply headroom of 1 V with a low-power consumption of 3.5 mW. PMID- 25133251 TI - Highly effective ex vivo gene manipulation to study kidney development using self complementary adenoassociated viruses. AB - BACKGROUND: Ex vivo culture of intact embryonic kidney has become a powerful system for studying renal development. However, few methods have been available for gene manipulation and have impeded the identification and investigation of genes in this developmental process. RESULTS: Here we systemically compared eight different serotypes of pseudotyped self-complementary adenoassociated viruses (scAAVs) transduction in cultured embryonic kidney with a modified culture procedure. We demonstrated that scAAV was highly effective in delivering genes into and expressing in compacted tissues. scAAV serotypes 2 and 8 exhibited higher efficiency of transduction compared to others. Expression kinetics assay revealed that scAAV can be used for gene manipulation at the study of UB branching and nephrogenesis. Repressing WT1 in cultured kidney using shRNA impairs tubule formation. We for the first time employed and validated scAAV as a gene delivery tool in cultured kidney. CONCLUSIONS: These findings are expected to expedite the use of the ex vivo embryonic kidney cultures for kidney development research. For other ex vivo cultured organ models, scAAV could also be a promising tool for organogenesis study. PMID- 25133253 TI - Video texture synthesis based on flow-like stylization painting. AB - The paper presents an NP-video rendering system based on natural phenomena. It provides a simple nonphotorealistic video synthesis system in which user can obtain a flow-like stylization painting and infinite video scene. Firstly, based on anisotropic Kuwahara filtering in conjunction with line integral convolution, the phenomena video scene can be rendered to flow-like stylization painting. Secondly, the methods of frame division, patches synthesis, will be used to synthesize infinite playing video. According to selection examples from different natural video texture, our system can generate stylized of flow-like and infinite video scenes. The visual discontinuities between neighbor frames are decreased, and we also preserve feature and details of frames. This rendering system is easy and simple to implement. PMID- 25133254 TI - Design and performance evaluation of a distributed OFDMA-based MAC protocol for MANETs. AB - In this paper, we propose a distributed MAC protocol for OFDMA-based wireless mobile ad hoc multihop networks, in which the resource reservation and data transmission procedures are operated in a distributed manner. A frame format is designed considering the characteristics of OFDMA that each node can transmit or receive data to or from multiple nodes simultaneously. Under this frame structure, we propose a distributed resource management method including network state estimation and resource reservation processes. We categorize five types of logical errors according to their root causes and show that two of the logical errors are inevitable while three of them are avoided under the proposed distributed MAC protocol. In addition, we provide a systematic method to determine the advertisement period of each node by presenting a clear relation between the accuracy of estimated network states and the signaling overhead. We evaluate the performance of the proposed protocol in respect of the reservation success rate and the success rate of data transmission. Since our method focuses on avoiding logical errors, it could be easily placed on top of the other resource allocation methods focusing on the physical layer issues of the resource management problem and interworked with them. PMID- 25133255 TI - Method to eliminate flux linkage DC component in load transformer for static transfer switch. AB - Many industrial and commercial sensitive loads are subject to the voltage sags and interruptions. The static transfer switch (STS) based on the thyristors is applied to improve the power quality and reliability. However, the transfer will result in severe inrush current in the load transformer, because of the DC component in the magnetic flux generated in the transfer process. The inrush current which is always 2 ~ 30 p.u. can cause the disoperation of relay protective devices and bring potential damage to the transformer. The way to eliminate the DC component is to transfer the related phases when the residual flux linkage of the load transformer and the prospective flux linkage of the alternate source are equal. This paper analyzes how the flux linkage of each winding in the load transformer changes in the transfer process. Based on the residual flux linkage when the preferred source is completely disconnected, the method to calculate the proper time point to close each phase of the alternate source is developed. Simulation and laboratory experiments results are presented to show the effectiveness of the transfer method. PMID- 25133256 TI - On the generalization of Lehmer problem and high-dimension Kloosterman sums. AB - For any fixed integer k >= 2 and integer r with (r, p) = 1, it is clear that there exist k integers 1 <= a i <= p - 1(i = 1, 2, ..., k) such that a 1 a 2 ? a k = r mod p. Let N(k, r; p) denote the number of all (a 1, a 2, ? a k ) such that a 1 a 2 ? a k = r mod p and 2?(a 1 + a 2 + ? + a k ). In this paper, we will use the analytic method and the estimate for high-dimension Kloosterman sums to study the asymptotic properties of N(k, r; p) and give two interesting asymptotic formulae for it. PMID- 25133257 TI - Mathematical model relating uniaxial compressive behavior of manufactured sand mortar to MIP-derived pore structure parameters. AB - The uniaxial compression response of manufactured sand mortars proportioned using different water-cement ratio and sand-cement ratio is examined. Pore structure parameters such as porosity, threshold diameter, mean diameter, and total amounts of macropores, as well as shape and size of micropores are quantified by using mercury intrusion porosimetry (MIP) technique. Test results indicate that strains at peak stress and compressive strength decreased with the increasing sand-cement ratio due to insufficient binders to wrap up entire sand. A compression stress strain model of normal concrete extending to predict the stress-strain relationships of manufactured sand mortar is verified and agreed well with experimental data. Furthermore, the stress-strain model constant is found to be influenced by threshold diameter, mean diameter, shape, and size of micropores. A mathematical model relating stress-strain model constants to the relevant pore structure parameters of manufactured sand mortar is developed. PMID- 25133258 TI - Cost-benefit analysis and emission reduction of energy efficient lighting at the Universiti Tenaga Nasional. AB - This paper reports the result of an investigation on the potential energy saving of the lighting systems at selected buildings of the Universiti Tenaga Nasional. The scope of this project includes evaluation of the lighting system in the Library, Admin Building, College of Engineering, College of Information Technology, Apartments, and COE Food court of the university. The main objectives of this project are to design the proper retrofit scenario and to calculate the potential electricity saving, the payback period, and the potential environmental benefits. In this survey the policy for retrofitting the old lighting system with the new energy saving LEDs starts with 10% for the first year and continues constantly for 10 years until all the lighting systems have been replaced. The result of the life cycle analysis reveals that after four years, the selected buildings will bring profit for the investment. PMID- 25133259 TI - Feasibility of using phase change materials to control the heat of hydration in massive concrete structures. AB - This paper presents experimental results that can be applied to select a possible phase change material (PCM), such as a latent heat material (LHM), to control the hydration heat in mass concrete structures. Five experimental tests (microconduction, simplified adiabatic temperature rise, heat, and compressive strength tests) were conducted to select the most desirable LHM out of seven types of inorganic PCM used in cement mortar and to determine the most suitable mix design. The results of these experimental tests were used to assess the feasibility of using PCM to reduce hydration heat in mass concrete that was examined. The experimental results show that cement mortar containing barium- [Ba(OH)2 . 8H2O] based PCM has the lowest amount of total hydration heat of the cement pastes. The barium-based PCM provides good latent heat properties that help to prevent volume change and microcracks caused by thermal stress in mass concrete. PMID- 25133260 TI - Assessment model of ecoenvironmental vulnerability based on improved entropy weight method. AB - Assessment of ecoenvironmental vulnerability plays an important role in the guidance of regional planning, the construction and protection of ecological environment, which requires comprehensive consideration on regional resources, environment, ecology, society and other factors. Based on the driving mechanism and evolution characteristics of ecoenvironmental vulnerability in cold and arid regions of China, a novel evaluation index system on ecoenvironmental vulnerability is proposed in this paper. For the disadvantages of conventional entropy weight method, an improved entropy weight assessment model on ecoenvironmental vulnerability is developed and applied to evaluate the ecoenvironmental vulnerability in western Jilin Province of China. The assessing results indicate that the model is suitable for ecoenvironmental vulnerability assessment, and it shows more reasonable evaluation criterion, more distinct insights and satisfactory results combined with the practical conditions. The model can provide a new method for regional ecoenvironmental vulnerability evaluation. PMID- 25133261 TI - The laws of natural deduction in inference by DNA computer. AB - We present a DNA-based implementation of reaction system with molecules encoding elements of the propositional logic, that is, propositions and formulas. The protocol can perform inference steps using, for example, modus ponens and modus tollens rules and de Morgan's laws. The set of the implemented operations allows for inference of formulas using the laws of natural deduction. The system can also detect whether a certain proposition a can be deduced from the basic facts and given rules. The whole protocol is fully autonomous; that is, after introducing the initial set of molecules, no human assistance is needed. Only one restriction enzyme is used throughout the inference process. Unlike some other similar implementations, our improved design allows representing simultaneously a fact a and its negation ~a, including special reactions to detect the inconsistency, that is, a simultaneous occurrence of a fact and its negation. An analysis of correctness, completeness, and complexity is included. PMID- 25133262 TI - Light-output enhancement of GaN-based light-emitting diodes with three dimensional backside reflectors patterned by microscale cone array. AB - Three-dimensional (3D) backside reflector, compared with flat reflectors, can improve the probability of finding the escape cone for reflecting lights and thus enhance the light-extraction efficiency (LEE) for GaN-based light-emitting diode (LED) chips. A triangle-lattice of microscale SiO2 cone array followed by a 16 pair Ti3O5/SiO2 distributed Bragg reflector (16-DBR) was proposed to be attached on the backside of sapphire substrate, and the light-output enhancement was demonstrated by numerical simulation and experiments. The LED chips with flat reflectors or 3D reflectors were simulated using Monte Carlo ray tracing method. It is shown that the LEE increases as the reflectivity of backside reflector increases, and the light-output can be significantly improved by 3D reflectors compared to flat counterparts. It can also be observed that the LEE decreases as the refractive index of the cone material increases. The 3D 16-DBR patterned by microscale SiO2 cone array benefits large enhancement of LEE. This microscale pattern was prepared by standard photolithography and wet-etching technique. Measurement results show that the 3D 16-DBR can provide 12.1% enhancement of wall plug efficiency, which is consistent with the simulated value of 11.73% for the enhancement of LEE. PMID- 25133263 TI - Comparative studies on bioactive constituents in hawk tea infusions with different maturity degree and their antioxidant activities. AB - Hawk tea (Litsea coreana var. lanuginose) is a very popular herbal tea in the southwest of China. According to the maturity degree of raw materials, Hawk tea can usually be divided into three types: Hawk bud tea (HB), Hawk primary leaf tea (HP), and Hawk mature leaf tea (HM). In this study, some of the bioactive constituents and antioxidant properties of the three kinds of Hawk tea infusions were comparatively investigated. The results showed that the contents of total flavonoids, vitamin C, and carbohydrates in Hawk bud tea infusion (HBI) were higher than those in Hawk primary leaf tea infusion (HPI) and Hawk mature leaf tea infusion (HMI). HPI had higher contents of total polyphenols and exhibited better DPPH radical scavenging activity and ferric reducing activity power. HBI could provide more effective protection against erythrocyte hemolysis. As age is going from bud to mature leaf, the ability to inhibit the formation of low density lipoprotein (LDL) conjugated diene and the loss of tryptophan fluorescence decreased. The bioactive constituents and antioxidant activities of Hawk tea infusions were significantly affected by the maturity degree of the raw material. PMID- 25133264 TI - Expression profiles of 12 late embryogenesis abundant protein genes from Tamarix hispida in response to abiotic stress. AB - Twelve embryogenesis abundant protein (LEA) genes (named ThLEA-1 to -12) were cloned from Tamarix hispida. The expression profiles of these genes in response to NaCl, PEG, and abscisic acid (ABA) in roots, stems, and leaves of T. hispida were assessed using real-time reverse transcriptase-polymerase chain reaction (RT PCR). These ThLEAs all showed tissue-specific expression patterns in roots, stems, and leaves under normal growth conditions. However, they shared a high similar expression patterns in the roots, stems, and leaves when exposed to NaCl and PEG stress. Furthermore, ThLEA-1, -2, -3, -4, and -11 were induced by NaCl and PEG, but ThLEA-5, -6, -8, -10, and -12 were downregulated by salt and drought stresses. Under ABA treatment, some ThLEA genes, such as ThLEA-1, -2, and -3, were only slightly differentially expressed in roots, stems, and leaves, indicating that they may be involved in the ABA-independent signaling pathway. These findings provide a basis for the elucidation of the function of LEA genes in future work. PMID- 25133265 TI - A simple quality assessment index for stereoscopic images based on 3D gradient magnitude. AB - We present a simple quality assessment index for stereoscopic images based on 3D gradient magnitude. To be more specific, we construct 3D volume from the stereoscopic images across different disparity spaces and calculate pointwise 3D gradient magnitude similarity (3D-GMS) along three horizontal, vertical, and viewpoint directions. Then, the quality score is obtained by averaging the 3D-GMS scores of all points in the 3D volume. Experimental results on four publicly available 3D image quality assessment databases demonstrate that, in comparison with the most related existing methods, the devised algorithm achieves high consistency alignment with subjective assessment. PMID- 25133266 TI - Low power upconversion mixer for medical remote sensing. AB - This work presents the design of a low power upconversion mixer adapted in medical remote sensing such as wireless endoscopy application. The proposed upconversion mixer operates in ISM band of 433 MHz. With the carrier power of -5 dBm, the proposed mixer has an output inferred 1 dB compression point of -0.5 dBm with a corresponding output third-order intercept point (OIP3) of 7.1 dBm. The design of the upconversion mixer is realized on CMOS 0.13 MUm platform, with a current consumption of 594 MUA at supply voltage headroom of 1.2 V. PMID- 25133267 TI - Differential responses of net ecosystem exchange of carbon dioxide to light and temperature between spring and neap tides in subtropical mangrove forests. AB - The eddy flux data with field records of tidal water inundation depths of the year 2010 from two mangroves forests in southern China were analyzed to investigate the tidal effect on mangrove carbon cycle. We compared the net ecosystem exchange (NEE) and its responses to light and temperature, respectively, between spring tide and neap tide inundation periods. For the most time of the year 2010, higher daytime NEE values were found during spring tides than during neap tides at both study sites. Regression analysis of daytime NEE to photosynthetically active radiation (PAR) using the Landsberg model showed increased sensitivity of NEE to PAR with higher maximum photosynthetic rate during spring tides than neap tides. In contrast, the light compensation points acquired from the regression function of the Landsberg model were smaller during spring tides than neap tides in most months. The dependence of nighttime NEE on soil temperature was lower under spring tide than under neap tides. All these results above indicated that ecosystem carbon uptake rates of mangrove forests were strengthened, while ecosystem respirations were inhibited during spring tides in comparison with those during neap tides, which needs to be considered in modeling mangrove ecosystem carbon cycle under future sea level rise scenarios. PMID- 25133268 TI - Antihepatoma activity of Artocarpus communis is higher in fractions with high artocarpin content. AB - Extracts from natural plants have been used in traditional medicine for many centuries worldwide. Artocarpus communis is one such plant that has been used to treat liver cirrhosis, hypertension, and diabetes. To our knowledge, this study is the first to investigate the antihepatoma activity of A. communis toward HepG2 and PLC/PRF/5 cells and the first to explore the relationship between antihepatoma activity and the active compound artocarpin content in different fractions of A. communis. A. communis methanol extract and fractions induced dose dependent reduction of tumor cell viability. DNA laddering analysis revealed that A. communis extract and fractions did not induce apoptosis in HepG2 and PLC/PRF/5 cells. Instead, acridine orange staining revealed that A. communis triggered autophagic cell death in a dose-dependent manner. The antihepatoma activity of A. communis is attributable to artocarpin. The fractions with the highest artocarpin content were also the fractions with the highest antihepatoma activity in the following order: dichloromethane fraction > methanol extract > ethyl acetate fraction > n-butanol fraction > n-hexane fraction. Taken together, A. communis showed antihepatoma activity through autophagic cell death. The effect was related to artocarpin content. Artocarpin could be considered an indicator of the anticancer potential of A. communis extract. PMID- 25133269 TI - Influence of the number of adhesive layers on adhesive interface properties under cariogenic challenge using streptococcus mutans. AB - PURPOSE: To test the hypothesis that the number of adhesive layers influences the adhesive interface properties under cariogenic challenge conditions using a Streptococcus mutans model. MATERIALS AND METHODS: Bovine teeth (n = 90) were sectioned into blocks of 5 mm and divided into two groups for microleakage testing (n = 60) and tensile bond strength testing (n = 30). In each group, the samples were subdivided into subgroups according to the number of adhesive layers applied on the dentin: one (SB1), two (SB2), and three adhesive layers (SB3). The samples of the control groups were placed in BHI broth medium supplemented with 2% sucrose without microorganisms, and the experimental groups were submitted to Streptococcus mutans American Type Culture Collection (ATCC) for 5 days. For the tensile strength test, samples were sectioned into 1-mm-thick slices and submitted to a constant load of 0.5 mm/min in a universal testing machine. Fractured surfaces were analyzed and characterized as adhesive, cohesive, or mixed. The microleakage test was performed with silver nitrate solution. RESULTS: In experimental groups, the tensile test revealed a statistically significant difference between the one- (18.59 +/- 5.3) and three-layer (11.28 +/- 5.0) groups (p < 0.001; ANOVA and Tukey's test). The adhesive failure mode was slightly more frequent in the one- (60%) and three-layer (80%) adhesive application groups. On the other hand, the microleakage levels of all experimental groups were statistically similar (Kruskal-Wallis; p > 0.05). CONCLUSION: The experimental conditions influenced tensile properties and failure modes of different adhesive interfaces; however, they did not influence microleakage. PMID- 25133270 TI - Influence of PEEK surface modification on surface properties and bond strength to veneering resin composites. AB - PURPOSE: To test the impact of mechanical and chemical treatments of PEEK on surface roughness (SR), surface free energy (SFE), and tensile bond strength (TBS) to veneering resin composites. MATERIALS AND METHODS: PEEK specimens (N = 680) were fabricated and divided into treatment groups (n = 170/group): 1. air abrasion (AIA); 2. etching with piranha solution (PIS); 3. air abrasion + piranha acid etching (AIP); and 4. no treatment (NO). Ten specimens of each treatment group were assessed with a contact angle measuring device and profilometer to determine SFE and SR, respectively. The remaining 160 specimens of each group were divided into subgroups according to coupling method (n = 32/subgroup): 1. Monobond Plus/ Heliobond (MH); 2. Visio.link (VL); 3. Clearfil Ceramic Primer (CCP); 4. Signum PEEK Bond (SPB); and 5. control, no coupling (CG). Specimens were veneered using Signum Composite/SiCo or Signum Ceramis/SiCe (both: n = 16), incubated in water (60 days at 37 degrees C) and thermocycled (5000 cycles of 5 degrees C/55 degrees C). TBS was measured and data analyzed by three- and one-way ANOVA, Kruskal-Wallis and Mann-Whitney tests (p < 0.05). RESULTS: A significant effect of surface treatment (p < 0.001) and coupling agent application (p < 0.001) on TBS was observed. AIA specimens with/without PIS showed the highest SFE, SR, and TBS. No differences were measured between PIS and NO, and between AIA and AIP. When no coupling agent was used, no adhesion was obtained. CCP resulted in low adhesion values, whereas MH, SPB, and VL exhibited increased TBS. No significant impact of the veneering resin composite on TBS was found (p = 0.424). CONCLUSION: AIA and AIP combined with VL, SPB, and MH can be recommended for clinical use. PMID- 25133271 TI - PI3 kinase enzymology on fluid lipid bilayers. AB - We report the use of fluid lipid bilayer membrane as a model platform to study the influence of the bilayer microenvironment and composition on the enzymology in membrane. As a model system we determined the enzyme kinetics on membranes for the transformation of bilayers containing phosphoinositol(4,5)-bisphosphate (PI(4,5)P2) to phosphoinositol(3,4,5)-trisphosphate (PI(3,4,5)P3) by the enzyme phosphoinositol-3-kinase (PI3K) using radiolabeled ATP. The activity of the enzyme was monitored as a function of the radioactivity incorporated within the bilayer. The transformation of PI(4,5)P2 to PI(3,4,5)P3 was determined using a mass strip assay. The fluidity of the bilayer was confirmed by Fluorescence Recovery After Photobleaching (FRAP) experiments. Kinetic simulations were performed based on Langmuir adsorption and Michaelis-Menton kinetics equations to generate the rate constants for the enzymatic reaction. The effect of cholesterol on the enzyme kinetics was studied by doping the bilayer with 1% cholesterol. This leads to significant reduction in reaction rate due to change in membrane microenvironment. This strategy provides a method to study the enzymology of various kinases and phosphatases occurring at the membrane and also how these reactions are affected by the membrane composition and surface microenvironment. PMID- 25133272 TI - Multiplex single particle analysis in microfluidics. AB - A straightforward way to measure separated micrometric sized particles in microfluidic flow is reported. The light scattering profile (LSP) of each single particle is fully characterized by using a CMOS-camera based small angle light scattering (SALS) apparatus, ranging from 2 degrees up to 30 degrees . To ensure controlled particle passage through the incident laser, a viscoelastic 3D alignment effect by viscoelastic induced particle migration has been implemented in a simple and cost-effective microfluidic device. Different polystyrene particle sizes are measured in microfluidic flows and the obtained scattering signatures are matched with the Lorenz-Mie based scattering theory. The results confirm the possibility of using this apparatus for real multiplex particle analyses in microfluidic particle flows. PMID- 25133274 TI - An asymmetric [3+2] cycloaddition of alkynes with oxiranes by selective C-C bond cleavage of epoxides: highly efficient synthesis of chiral furan derivatives. AB - An efficient enantioselective [3+2] cycloaddition of alkynes with oxiranes via selective C-C bond cleavage of epoxides was developed. A number of optically active 2,5-dihydrofurans were obtained in excellent yields (up to 99%) and enantioselectivities (up to 95% ee) under mild reaction conditions. Moreover, chiral tetrahydrofuran could also be obtained by cycloaddition of alkene and oxirane or hydrogenation of chiral 2,5-dihydrofuran. PMID- 25133275 TI - A selective and sensitive fluorescent albumin probe for the determination of urinary albumin. AB - In this communication, we report a simple albumin probe based on a fluorescent molecular rotor for the detection of trace albumin levels in urine. In the presence of albumin, the probe exhibits remarkable 400-fold fluorescence enhancement with high selectivity and sensitivity. The probe was successfully applied in the quantitative detection of urinary albumin. PMID- 25133273 TI - Desalting protein ions in native mass spectrometry using supercharging reagents. AB - Effects of the supercharging reagents m-NBA and sulfolane on sodium ion adduction to protein ions formed using native mass spectrometry were investigated. There is extensive sodium adduction on protein ions formed by electrospray ionization from aqueous solutions containing millimolar concentrations of NaCl, which can lower sensitivity by distributing the signal of a given charge state over multiple adducted ions and can reduce mass measuring accuracy for large proteins and non covalent complexes for which individual adducts cannot be resolved. The average number of sodium ions adducted to the most abundant ion formed from ten small (8.6-29 kDa) proteins for which adducts can be resolved is reduced by 58% or 80% on average, respectively, when 1.5% m-NBA or 2.5% sulfolane are added to aqueous solutions containing sodium compared to without the supercharging reagent. Sulfolane is more effective than m-NBA at reducing sodium ion adduction and at preserving non-covalent protein-ligand and protein-protein interactions. Desalting with 2.5% sulfolane enables detection of several glycosylated forms of 79.7 kDa holo-transferrin and NADH bound to the 146 kDa homotetramer LDH, which are otherwise unresolved due to peak broadening from extensive sodium adduction. Although sulfolane is more effective than m-NBA at protein ion desalting, m-NBA reduces salt clusters at high m/z and can increase the signal-to-noise ratios of protein ions by reducing chemical noise. Desalting is likely a result of these supercharging reagents binding sodium ions in solution, thereby reducing the sodium available to adduct to protein ions. PMID- 25133277 TI - Ankle-brachial index in patients with ischaemic stroke. PMID- 25133278 TI - Pure hereditary spastic paraplegia due to a de novo mutation in the NIPA1 gene. PMID- 25133276 TI - Recombinant murine growth hormone particles are more immunogenic with intravenous than subcutaneous administration. AB - Evaluation and mitigation of the risk of immunogenicity to protein aggregates and particles in therapeutic protein products remains a primary concern for drug developers and regulatory agencies. To investigate how the presence of protein particles and the route of administration influence the immunogenicity of a model therapeutic protein, we measured the immune response in mice to injections of formulations of recombinant murine growth hormone (rmGH) that contained controlled levels of protein particles. Mice were injected twice over 6 weeks with rmGH formulations via the subcutaneous, intraperitoneal, or intravenous (i.v.) routes. In addition to soluble, monomeric rmGH, the samples prepared contained either nanoparticles of rmGH or both nano- and microparticles of rmGH.The appearance of anti-rmGH IgG1, IgG2a, IgG2b, IgG2c, and IgG3 titers following the second injection of both preparations implies that multiple mechanisms contributed to the immune response. No dependence of the immune response on particle size and distribution was observed. The immune response measured after the second injection was most pronounced when i.v. administration was used. Despite producing high anti-rmGH titers mice appeared to retain the ability to properly regulate and use endogenous growth hormone. PMID- 25133279 TI - Intravenous thrombolysis in stroke patients receiving rivaroxaban. PMID- 25133280 TI - Paraneoplastic motor neuron disease associated with breast cancer. PMID- 25133281 TI - Inquiry to inclusion of papers among Turkey's 2012 cardiovascular publications. Author's reply. PMID- 25133282 TI - Mean platelet volume may not be related to clopidogrel resistance in patients with acute coronary syndrome. Author's reply. PMID- 25133283 TI - Health warnings about obesity: King's Festival of Food and Ideas. PMID- 25133284 TI - [Cardiovascular magnetic resonance imaging in patients with acute chest pain]. AB - Acute chest pain is a common reason for presentation to the emergency department. It can be caused by a wide variety of diseases, some of which are potentially lethal, so it must be diagnosed quickly. The rise of computed tomography to evaluate patients with acute chest pain is noteworthy. However, computed tomography is not without limitations in this context. Cardiovascular magnetic resonance imaging is a potentially useful technique in this group of patients, although its availability and the time required for examinations restrict its use to specific indications. PMID- 25133285 TI - Wnt-signalling: A new direction for alzheimer disease? PMID- 25133286 TI - Why are cancer drugs so costly? PMID- 25133287 TI - [Acute perforated eardrum - patching with hyaluronic acid or spontaneous healing?]. PMID- 25133288 TI - [Lesions of the submandibular glands - contrast-enhanced ultrasound for non invasive diagnosis]. PMID- 25133289 TI - [Tips & tricks--collar button technique: safe and patient friendly myringoplasty technique]. AB - Background: The inlay cartilage butterfly myringoplasty is a simple technique with few complications for closure of tympanic membrane defects introduced by Eavey 1998, but still not often used. Its advantages consist in avoiding of exposure the tympanic cavity and possible blunting, option to operate both ears at once, safe local anaesthesia, reduction of operation time and cost, minimal postoperative care and patient comfort. Patients and Methods: We operated 10 patients using a to date not described simple cartilage transplant without perichondrium. Reason, localisation, extent and duration of the defect as well as complications, patient assessment and pure tone audiogram were analysed. Results: All defects were closed six months postoperative. Seven patients rated hearing as improved, two as non-changed and one patient showed deafness in the pure tone audiogram pre- and postoperative. The average air-bone gap of the thresholds at frequencies 0.5, 1, 2 and 3 kHz was 8.6 dB postoperative as compared to 16.3 dB preoperative. It could be shown that pure cartilage transplants without perichondrium used for defects up to 6mm in diameter were enwrapped by the tympanic membrane and covered by capillaries. Conclusion: The inlay cartilage butterfly myringoplasty is a safe and gentle technique for tympanic membrane defect closure. PMID- 25133290 TI - Comparison of oxidation resistance of UHMWPE and POM in H2O2 solution from ReaxFF reactive molecular dynamics simulations. AB - The oxidation mechanism of ultra-high-molecular-weight polyethylene (UHMWPE) and polyoxymethylene (POM) in hydrogen peroxide solution was investigated by molecular dynamics (MD) simulations via reactive force field (ReaxFF) method. MD results from ReaxFF suggested that UHMWPE provided better antioxidation activity at high temperature (>373 K) than its POM counterpart in the same concentration of hydrogen peroxide solution. Furthermore, POM was relatively more susceptible to erosion and swelling because of the infiltration of H2O2 solution. Calculations of the diffusion coefficient at different temperatures permit further understanding of the chemical phenomena involved in the level of oxidation in the course of MD simulations. Results of the simulations are generally consistent with the previous experimental available in literature. The simulations also provide new insights into understanding the mechanism resulting oxidation products among the interested polymers. PMID- 25133292 TI - Development of bifunctional chelates bearing hydroxamate arms for highly efficient (64)Cu radiolabeling. AB - Convenient approaches for the synthesis of DOTHA2 and NOTHA2, two cyclic bifunctional chelates (BFCs) bearing hydroxamate arms, have been developed. These novel BFCs coordinate (64)Cu with fast kinetics at room temperature in a wide range of concentrations and pH. The corresponding radiochemical complexes showed high stability, low residual activity in various tissues, and fast clearance in normal mice. The ability to conjugate DOTHA2 to both a small peptide and a large protein is also reported. PMID- 25133293 TI - Preparation of biointeractive glycoprotein-conjugated hydrogels through metabolic oligosacchalide engineering. AB - In the current study, synthetic hydrogels containing metabolically engineered glycoproteins of mammalian cells were prepared for the first time and selectin mediated cell adhesion on the hydrogel was demonstrated. A culture of HL-60 cells was supplemented with an appropriate volume of aqueous solution of N-methacryloyl mannosamine (ManMA) to give a final concentration of 5 mM. The cells were then incubated for 3 days to deliver methacryloyl groups to the glycoproteins of the cells. A transparent hydrogel was formed via redox radical polymerization of methacryloyl functionalized glycoproteins with 2-methacryloyloxyethyl phosphorylcholine and a cross-linker. Conjugation of the glycoproteins into the hydrogel was determined using Coomassie brilliant blue (CBB) and periodic acid Schiff (PAS) staining. The surface density of P-selectin glycoprotein ligand-1 (PSGL-1) on the hydrogels was also detected using gold-colloid-labeled immunoassay. Finally, selectin-mediated cell adhesion on hydrogels containing glycoproteins was demonstrated. Selectin-mediated cell adhesion is considered an essential step in the progression of various diseases; therefore, hydrogels having glycoproteins could be useful in therapeutic and diagnostic applications. PMID- 25133294 TI - Peroxides as "switches" of dialkyl H-phosphonate: two mild and metal-free methods for preparation of 2-acylbenzothiazoles and dialkyl benzothiazol-2 ylphosphonates. AB - Two mild and metal-free methods for the preparation of two kinds of important benzothiazole derivatives, 2-acylbenzothiazoles and dialkyl benzothiazol-2 ylphosphonates, respectively, were developed. The dialkyl H-phosphonate (RO)2P(O)H exists in equilibrium with its tautomer dialkyl phosphite (RO)2POH. TBHP triggered alpha-carbon-centered phosphite radical formation, whereas DTBP triggered phosphorus-centered phosphonate radical formation. The two types of radicals led respectively to two different reaction processes, the direct C2 acylation of benzothiazoles and C2-phosphonation of benzothiazoles. PMID- 25133295 TI - Discovery of a highly selective caspase-3 substrate for imaging live cells. AB - Caspases are a family of cysteine proteases that are well-known for their roles in apoptosis and inflammation. Recent studies provide evidence that caspases are also integral to many additional cellular processes, such as differentiation and proliferation. Likewise, aberrant caspase activity has been implicated in the progression of several diseases, including neurodegenerative disorders, cancer, cardiovascular disease, and sepsis. These observations establish the importance of caspases to a diverse array of physiological functions and future endeavors will undoubtedly continue to elucidate additional processes that require caspase activity. Unfortunately, the existence of 11 functional human caspases, with overlapping substrate specificities, confounds the ability to confidently assign one or more isoforms to biological phenomena. Herein, we characterize a first-in class FRET substrate that is selectively recognized by active caspase-3 over other initiator and executioner caspases. We further apply this substrate to specifically image caspase-3 activity in live cells undergoing apoptosis. PMID- 25133296 TI - Dynamics of ADHD in familial contexts: perspectives from children and parents and implications for practitioners. AB - This article provides in-depth insights on the bidirectional dynamics between parents and their children with attention deficit hyperactivity disorder (ADHD). Five family units (8 parents, 5 children, N = 13) participated in this study. Parents and their child with ADHD were interviewed individually in their homes. Stressful moments of parent-child dynamics revolved around managing their child's behavior and doing homework. Findings highlight the child's agency and power of influence, and the possible recovery of negative dynamics. It is recommended that practitioners adopt the strengths perspective in working with these families and incorporate child's agency and bidirectional dynamics in interventions. PMID- 25133297 TI - In the front line: the impact of specialist training for hospital physicians in children at risk on their collaboration with social workers. AB - Until recently, dealing with children at risk in Israeli hospitals was almost exclusively the domain of medical social workers. Suspected cases of abuse or neglect must be identified in real-time, during the child's short stay in the hospital, and the decision of whether or not to report the case, and to whom (law enforcement or welfare authorities), must be made. The recognition that effective treatment also demands the involvement of physicians led to the development of an intensive training program for hospital-pediatricians. The current study, based on in-depth interviews with the doctors who participated in the program and the social workers who work with them at 14 hospitals in Israel, examined the impact of the training on cooperation between the two groups, seeking to determine whether the doctors' increased familiarity with the social work profession enhanced team-work. Phenomenological analysis of the interviews revealed several themes, indicating greater collaboration between the doctors and social workers. However, the participants also noted increased friction between the two groups. Possible explanations and practical recommendations for enhancing the potential effectiveness of such collaborations are offered. The study has implications for designing similar training programs as well as for improving the dynamics between the two professions. PMID- 25133298 TI - Families with children with medical complexity and self-management of care: a systematic review of the literature. AB - This review analyzes the quantitative literature on children with medical complexity (CMC). Using the Pediatric Self-Management Model, evidence is summarized into facilitators and barriers to self-management. Current quantitative research focuses on the caregiver burden in families with CMC. A model for social work with families with CMC was introduced in response to these findings. A re-envisioned model allows the child with medical complexity to be seen as whole rather than focusing on typically deficit-based areas of medical specialty or service provision. PMID- 25133299 TI - Screening, testing, and reporting for drug and alcohol use on labor and delivery: a survey of Maryland birthing hospitals. AB - Recent amendments to the Child Abuse Prevention and Treatment Act tie the receipt of federal block grants to mandatory reporting of substance-exposed newborns. To determine rates of screening, testing, and reporting of drug and alcohol use at the time of delivery, we administered a telephone survey of nursing managers and perinatal social workers at Maryland birthing hospitals. Of the 34 hospitals, 31 responded (response rate 91%). Although 97% of hospitals reported universal screening, only 6% used a validated instrument. Testing was reported by 94% with 45% reporting universal maternal testing and 7% universal newborn testing. Only 32% reported obtaining maternal consent prior to testing. There is significant heterogeneity in screening and testing for substance use in birthing hospitals. Given federal reporting mandates, state-level practices need to be standardized. PMID- 25133300 TI - Caregivers' experience in patients with chronic diseases. AB - The aim of this study was to describe the characteristics of caregivers of patients with chronic diseases, assess their perceived burden, and investigate factors influencing this burden. Seventy-three patient-attendants (43 men and 30 women) participated in the pilot-research conducted by two clinics. Of them, 68% attended patients with a malignant disease and 32% attended patients in the end stage of renal disease. Based on questionnaire data, the influence of the social support was studied, in particular that of family members or through state programmers. Family members are the primary caregivers (spouses 51%, children 29%, and others 20%). Psychological support is the main important help that they need and there are a small number of caregivers who have access to a network of medical and social support. It is found that the family still remains the main supporting mechanism for attendants and patients in our population. PMID- 25133301 TI - Long-term care insurance in China: public or private? AB - China faces an overwhelming and urgent need for long-term care (LTC). We explored long-term care insurance (LTCI) plans in China and the factors associated with each plan's contribution rate. A cross-sectional survey of 814 residents (18-59 years) was conducted to assess the expectations of elderly care, public and private LTCI features. Public LTCI may be more popular whether in terms of participation or contribution. The factors associated with public LTCI contribution rate were healthcare costs, household income, and number of daughters; for private LTCI, the factors were the proportion of living expenditures, worry about future care problems, and healthcare costs. Policymakers should develop public LTCI as a solid foundation and improve private LTCI as a substitute to meet the urgent LTC needs in China. PMID- 25133302 TI - Nanocrystal grain growth and device architectures for high-efficiency CdTe ink based photovoltaics. AB - We study the use of cadmium telluride (CdTe) nanocrystal colloids as a solution processable "ink" for large-grain CdTe absorber layers in solar cells. The resulting grain structure and solar cell performance depend on the initial nanocrystal size, shape, and crystal structure. We find that inks of predominantly wurtzite tetrapod-shaped nanocrystals with arms ~5.6 nm in diameter exhibit better device performance compared to inks composed of smaller tetrapods, irregular faceted nanocrystals, or spherical zincblende nanocrystals despite the fact that the final sintered film has a zincblende crystal structure. Five different working device architectures were investigated. The indium tin oxide (ITO)/CdTe/zinc oxide structure leads to our best performing device architecture (with efficiency >11%) compared to others including two structures with a cadmium sulfide (CdS) n-type layer typically used in high efficiency sublimation-grown CdTe solar cells. Moreover, devices without CdS have improved response at short wavelengths. PMID- 25133303 TI - A longitudinal study of an intervention to improve road safety climate: climate as an organizational boundary spanner. AB - This study presents and tests an intervention to enhance organizational climate and expands existing conceptualization of organizational climate to include its influence on employee behaviors outside the organization's physical boundaries. In addition, by integrating the literatures of climate and work-family interface, the study explored climate spillover and crossover from work to the home domain. Focusing on an applied practical problem within organizations, we investigated the example of road safety climate and employees' and their families' driving, using a longitudinal study design of road safety intervention versus control groups. Results demonstrated that the intervention increased road safety climate and decreased the number of traffic violation tickets and that road safety climate mediated the relationship between the intervention and the number of traffic violation tickets. Road safety climate spilled over to the family domain but did not cross over to influence family members' driving. PMID- 25133304 TI - A meta-analysis of the relationship between general mental ability and nontask performance. AB - Although one of the most well-established research findings in industrial organizational psychology is that general mental ability (GMA) is a strong and generalizable predictor of job performance, this meta-analytically derived conclusion is based largely on measures of task or overall performance. The primary purpose of this study is to address a void in the research literature by conducting a meta-analysis to determine the direction and magnitude of the correlation of GMA with 2 dimensions of nontask performance: counterproductive work behaviors (CWB) and organizational citizenship behaviors (OCB). Overall, the results show that the true-score correlation between GMA and CWB is essentially 0 (-.02, k = 35), although rating source of CWB moderates this relationship. The true-score correlation between GMA and OCB is positive but modest in magnitude (.23, k = 43). The 2nd purpose of this study is to conduct meta-analytic relative weight analyses to determine the relative importance of GMA and the five-factor model (FFM) of personality traits in predicting nontask and task performance criteria. Results indicate that, collectively, the FFM traits are substantially more important for CWB than GMA, that the FFM traits are roughly equal in importance to GMA for OCB, and that GMA is substantially more important for task and overall job performance than the FFM traits. Implications of these findings for the development of optimal selection systems and the development of comprehensive theories of job performance are discussed along with study limitation and future research directions. (PsycINFO Database Record (c) 2014 APA, all rights reserved). PMID- 25133305 TI - DUI offenders' experience with an ignition interlock program: comparing those who have and have not adapted from their primary drinking location. AB - OBJECTIVE: The purpose of this study was to compare driving under the influence (DUI) offenders on an alcohol ignition interlock program who had or had not changed their primary drinking context from a bar/restaurant where they might be required to drive after drinking before the interlock was installed to drinking at home where driving would not be likely to be required following interlock installation. METHODS: A total of 171 DUI offenders who were on an ignition interlock program completed a web-based survey. All of these offenders reported that they drank primarily in a bar/restaurant before the interlock was installed. These offenders were classified into 2 groups: adapters who said they currently drink at home and nonadapters who said they still drink in a bar/restaurant. Measures were made of their reported drinking, driving patterns, perceptions of the likely outcomes of being on the interlock, perceived effectiveness of various prevention strategies, and demographic characteristics. Chi-square and t-test analyses were used to compare these 2 groups. RESULTS: Adapters and nonadapters did not differ with regard to any of the demographic characteristics, whether they were a first-time DUI offender, the length of time in the interlock program, number of lockouts (being blocked from starting their cars) they had experienced, miles driven per week, or current driving patterns since being on the interlock program. Adapters were more likely to report changing their drinking plans and habits. Currently they reported fewer drinks per occasion than nonadapters. They were more likely to report reducing the amount they drink, solo drinking or only drinking with a spouse/significant other, and changing their drinking plans and habits. They were also more likely to say that the interlock reminded them to limit their drinking after it is removed and that it might have longer term benefits in preventing future DUIs. They were also more receptive to interventions that might help them separate their drinking from their driving. CONCLUSIONS: Interlock clients who report that they have altered their drinking context and a willingness to receive programs that help them separate their drinking from their driving may be more receptive to and benefit from ignition interlock programs. PMID- 25133306 TI - Is cerebrospinal fluid obtained for diagnostic purpose a good material for biomarker studies in amyotrophic lateral sclerosis? AB - The cerebrospinal fluid (CSF) used for identification of molecular biomarkers in amyotrophic lateral sclerosis (ALS) is mainly obtained from lumbar puncture (LP) performed to exclude other causes of motor neuron damage. AIM: The aim of the study was to analyze whether CSF of ALS patients obtained for diagnostic purposes is suitable for biomarker studies in the entire ALS population. MATERIAL AND METHODS: We analyzed the medical data, LP frequency and CSF parameters in 568 ALS patients. RESULTS: LP was performed in 34% of cases. Patients who underwent LP were significantly younger and more frequently presented limb onset ALS, there were no differences in the clinical phenotypes. CONCLUSION: CSF obtained for diagnostic purposes can be used for biomarkers studies in ALS. PMID- 25133309 TI - 3D artificial bones for bone repair prepared by computed tomography-guided fused deposition modeling for bone repair. AB - The medical community has expressed significant interest in the development of new types of artificial bones that mimic natural bones. In this study, computed tomography (CT)-guided fused deposition modeling (FDM) was employed to fabricate polycaprolactone (PCL)/hydroxyapatite (HA) and PCL 3D artificial bones to mimic natural goat femurs. The in vitro mechanical properties, in vitro cell biocompatibility, and in vivo performance of the artificial bones in a long load bearing goat femur bone segmental defect model were studied. All of the results indicate that CT-guided FDM is a simple, convenient, relatively low-cost method that is suitable for fabricating natural bonelike artificial bones. Moreover, PCL/HA 3D artificial bones prepared by CT-guided FDM have more close mechanics to natural bone, good in vitro cell biocompatibility, biodegradation ability, and appropriate in vivo new bone formation ability. Therefore, PCL/HA 3D artificial bones could be potentially be of use in the treatment of patients with clinical bone defects. PMID- 25133308 TI - Early-lethal Costello syndrome due to rare HRAS Tandem Base substitution (c.35_36GC>AA; p.G12E)-associated pulmonary vascular disease. AB - Costello syndrome is a rare, autosomal-dominant syndrome caused by activating missense mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS), most often p.G12S. Several rare mutations have consistently been associated with a more severe phenotype that is often lethal in infancy. Cause of death is most often respiratory failure, with hypertrophic cardiomyopathy playing a significant role in morbidity. Impaired fibroblast elastogenesis is thought to contribute to the Costello phenotype, but reports of histologic evidence of disordered elastogenesis at autopsy are limited. We report a patient with Costello syndrome due to a rare tandem base substitution (c.35_36GC>AA) resulting in the p.G12E missense change. The proband died at the age of 3 months from respiratory failure, with minimal evidence of cardiomyopathy. The autopsy disclosed pulmonary vascular dysplasia affecting small arteries and veins associated with abnormal elastin distribution in tortuous dilated arteries and veins, with nonuniform wall thickness and semiobstructive lesions at artery branch points typical of early pulmonary hypertensive vascular disease. Elastic fibers in the dermis were abnormally short and fragmented. This case suggests that disordered elastogenesis in the pulmonary vasculature and undiagnosed (or underdiagnosed) pulmonary hypertension may contribute to morbidity in patients with Costello syndrome. PMID- 25133311 TI - Emergence of DNA-encapsulating liposomes from a DNA-lipid blend film. AB - Spontaneous generation of DNA-enclosing liposomes from a DNA-lipid blend film is investigated. The special properties of the lipid vesicles, namely, micrometer size, unilamellarity, and dense polymer encapsulation acquired by the dehydration rehydration process, are physicochemically revealed. We found that the formation of giant unilamellar vesicles encapsulating DNAs are governed by micropatterns of the films, such as dots and network patterns. From the results, we proposed a plausible physical mechanism for the dehydration-rehydration process, making it possible to optimize the encapsulation of any agent. PMID- 25133310 TI - NanoScript: a nanoparticle-based artificial transcription factor for effective gene regulation. AB - Transcription factor (TF) proteins are master regulators of transcriptional activity and gene expression. TF-based gene regulation is a promising approach for many biological applications; however, several limitations hinder the full potential of TFs. Herein, we developed an artificial, nanoparticle-based transcription factor, termed NanoScript, which is designed to mimic the structure and function of TFs. NanoScript was constructed by tethering functional peptides and small molecules called synthetic transcription factors, which mimic the individual TF domains, onto gold nanoparticles. We demonstrate that NanoScript localizes within the nucleus and initiates transcription of a reporter plasmid by over 15-fold. Moreover, NanoScript can effectively transcribe targeted genes on endogenous DNA in a nonviral manner. Because NanoScript is a functional replica of TF proteins and a tunable gene-regulating platform, it has great potential for various stem cell applications. PMID- 25133312 TI - Dehalogenation of aromatics by nucleophilic aromatic substitution. AB - Nucleophilic aromatic substitution has been implicated as a mechanism for both the biotic and abiotic hydrodehalogenation of aromatics. Two mechanisms for the aqueous dehalogenation of aromatics involving nucleophilic aromatic substitution with hydride as a nucleophile are investigated using a validated density functional and continuum solvation protocol. For chlorinated and brominated aromatics, nucleophilic addition ortho to carbon-halogen bonds via an anionic intermediate is predicted to be the preferred mechanism in the majority of cases, while concerted substitution is predicted to be preferred for most fluorinated aromatics. Nucleophilic aromatic substitution reactions with the hydroxide and hydrosulfide anions as nucleophiles are also investigated and compared. PMID- 25133307 TI - Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity. AB - Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body. Protein protein interactions play a critical role in this process. Historically, the study of CYP-protein interactions has focused on their electron transfer partners and allosteric mediators, cytochrome P450 reductase and cytochrome b5. However, CYPs can bind other proteins that also affect CYP function. Some examples include the progesterone receptor membrane component 1, damage resistance protein 1, human and bovine serum albumin, and intestinal fatty acid binding protein, in addition to other CYP isoforms. Furthermore, disruption of these interactions can lead to altered paths of metabolism and the production of toxic metabolites. In this review, we summarize the available evidence for CYP protein-protein interactions from the literature and offer a discussion of the potential impact of future studies aimed at characterizing noncanonical protein-protein interactions with CYP enzymes. PMID- 25133313 TI - Ligularia fischeri extract protects against oxidative-stress-induced neurotoxicity in mice and PC12 cells. AB - Alzheimer's disease (AD) is pathologically characterized by the presence of amyloid plaques in brain and the overproduction of amyloid beta (Abeta), leading to learning and memory impairment and intense oxidative stress. In this study, the protective effect of Ligularia fischeri extract was investigated using PC12 cells. L. fischeri extract attenuated hydrogen-peroxide-induced DNA fragmentation in cells. In vivo behavioral tests were performed to examine the effects of the extract on amyloid-beta peptide1-42-induced impairment of learning and memory in mice. A diet containing the extract increased alternation behaviors in the Y-maze test and step-through latency of passive avoidance task. Moreover, we found that consumption of the extract decreased lipid peroxidation in a biochemical study of brain tissue in mice. High-performance liquid chromatography was used to identify the active compounds in the extract. These results suggest that L. fischeri extract could be protective against Abeta-induced neurotoxicity, possibly due to the antioxidative capacity of its constituent, 3-O-caffeoylquinic acid. PMID- 25133315 TI - Effects of urban sprawl and vehicle miles traveled on traffic fatalities. AB - OBJECTIVE: Previous research suggests that urban sprawl increases auto-dependency and that excessive auto use increases the risk of traffic fatalities. This indirect effect of urban sprawl on traffic fatalities is compared to non-vehicle miles traveled (VMT)-related direct effect of sprawl on fatalities. METHODS: We conducted a path analysis to examine the causal linkages among urban sprawl, VMT, traffic fatalities, income, and fuel cost. The path diagram includes 2 major linkages: the direct relationship between urban sprawl and traffic fatalities and the indirect effect on fatalities through increased VMT in sprawling urban areas. To measure the relative strength of these causal linkages, path coefficients are estimated using data collected nationally from 147 urbanized areas in the United States. RESULTS: Through both direct and indirect paths, urban sprawl is associated with greater numbers of traffic fatalities, but the direct effect of sprawl on fatalities is more influential than the indirect effect. CONCLUSIONS: Enhancing traffic safety can be achieved by impeding urban sprawl and encouraging compact development. On the other hand, policy tools reducing VMT may be less effective than anticipated for traffic safety. PMID- 25133316 TI - Synthesis and arm dissociation in molecular stars with a spoked wheel core and bottlebrush arms. AB - Unique star-like polymeric architectures composed of bottlebrush arms and a molecular spoked wheel (MSW) core were prepared by atom transfer radical polymerization (ATRP). A hexahydroxy-functionalized MSW (MSW(6-OH)) was synthesized and converted into a six-fold ATRP initiator (MSW(6-Br)). Linear chain arms were grafted from MSW(6-Br) and subsequently functionalized with ATRP moieties to form six-arm macroinitiators. Grafting of side chains from the macroinitiators yielded four different star-shaped bottlebrushes with varying lengths of arms and side chains, i.e., (450-g-20)6, (450-g-40)6, (300-g-60)6, and (300-g-150)6. Gel permeation chromatography analysis and molecular imaging by atomic force microscopy confirmed the formation of well-defined macromolecules with narrow molecular weight distributions. Upon adsorption to an aqueous substrate, the bottlebrush arms underwent prompt dissociation from the MSW core, followed by scission of covalent bonds in the bottlebrush backbones. The preferential cleavage of the arms is attributed to strong steric repulsion between bottlebrushes at the MSW branching center. Star-shaped macroinitiators may undergo aggregation which can be prevented by sonication. PMID- 25133314 TI - SIN3 is critical for stress resistance and modulates adult lifespan. AB - Coordinate control of gene activity is critical for fitness and longevity of an organism. The SIN3 histone deacetylase (HDAC) complex functions as a transcriptional repressor of many genes. SIN3-regulated genes include those that encode proteins affecting multiple aspects of mitochondrial function, such as energy production and stress responsiveness, important for health maintenance. Here we used Drosophila melanogaster as a model organism to examine the role of SIN3 in the regulation of fitness and longevity. Adult flies with RNA interference (RNAi) induced knockdown expression of Sin3A have reduced climbing ability; an activity that likely requires fully functional mitochondria. Additionally, compared to wild type, adult Sin3A knockdown flies were more sensitive to oxidative stress. Interestingly, media supplementation with the antioxidant glutathione largely restored fly tolerance to oxidative stress. Although Sin3A knockdown flies exhibited decreased longevity compared to wild type, no significant changes in expression of many well-categorized aging genes were observed. We found, however, that Sin3A knockdown corresponded to a significant reduction in expression of genes encoding proteins involved in the de novo synthesis of glutathione. Taken together, the data support a model whereby SIN3 regulates a gene expression program required for proper mitochondrial function and effective stress response during adulthood. PMID- 25133318 TI - Interhemispheric collaboration during digit and dot number-matching in younger and older adults. AB - Digit and dot number-matching stimuli were used to replicate findings reported for younger adults by Patel and Hellige (2007) and to explore whether performance would differ for younger versus older participants. Participants were to make numerical matches of digits only, dots only, and digits and dots mixed conditions to determine whether reaction time (RT), percentage error, and efficiency scores that combine latency and accuracy for match trials were better on within- versus across-hemisphere trials. Sixty-six younger and 42 older participants were screened with the Mini-Mental State Examination (MMSE) and the Geriatric Depression Scale. They performed the three experimental conditions and were assessed with Digit Span Forward and Backward subscales from the Wechsler Adult Intelligence Scale-III. Results for younger adults demonstrated a within hemisphere advantage for the Digits and Mixed conditions and an across-hemisphere advantage for the Dots condition, consistent with previous literature. Older participants showed a stronger within-hemisphere advantage for the Digits condition compared with younger participants and no advantage for within- or across-hemisphere processing for the Mixed condition when RT was considered, but they performed similarly to younger adults when efficiency scores were used and showed a relative across-hemisphere advantage for the Dots condition. Although RT suggests age-related differences in how information is distributed across the hemispheres of the brain, more comprehensive efficiency scores indicate that younger and older adults appear to use similar strategies in the coordination of interhemispheric transfer of information. MMSE scores regardless of age were related to type of task but not to across- versus within-hemisphere performance. PMID- 25133317 TI - The posteromedial region of the default mode network shows attenuated task induced deactivation in psychopathic prisoners. AB - OBJECTIVE: Psychopathy is a personality disorder with symptoms that include lack of empathy or remorse, antisocial behavior, and excessive self-focus. Previous neuroimaging studies have linked psychopathy to dysfunction in the default mode network (DMN), a brain network that deactivates during externally focused tasks and is more engaged during self-referential processing. Specifically, the DMN has been found to remain relatively active in individuals with psychopathic tendencies during externally focused tasks, suggesting a failure to properly deactivate. However, the exact extent and nature of task-induced DMN dysfunction is poorly understood, including (a) the degree to which specific DMN subregions are affected in criminal psychopaths, and (b) how activity in these subregions relates to affective/interpersonal and antisocial/lifestyle traits of psychopathy. METHOD: We performed a group independent component analysis to assess DMN activation during a Go/NoGo task in a group of 22 high-psychopathy and 22 low-psychopathy prisoners. The identified group-level DMN was parcellated into 6 subregions, and group differences in task-induced activity were examined. RESULTS: In general, DMN subregions failed to deactivate beneath baseline in the high-psychopathy group. A group comparison with the low-psychopathy group localized this attenuated task-induced deactivation to the posteromedial cortical (mPC) region of the DMN. Moreover, multiple regression analyses revealed that activity in the mPC was associated with affective/interpersonal traits of psychopathy. CONCLUSION: These findings suggest that attenuated deactivation of the mPC subregion of the DMN is intrinsic to psychopathy, and is a pattern that may be more associated with affective psychopathic traits, including lack of concern for others. PMID- 25133320 TI - Parenthood and Physical Activity in Young Adults: A Qualitative Study. AB - BACKGROUND: New parents have to adjust to less sleep, less free time, and more responsibility as a result of having a child. The purpose of this study was to examine how having a child impacts the physical activity (PA) beliefs and behaviors of new parents over a 2- to 3-year time period. METHODS: Participants included 49 men and women (31% men, 96% white) who did not have a child at baseline (26.3 +/- 1.1 years old) but did have a child at the time of follow-up (28.9 +/- 1.7 years old). The child's mean age at follow-up was 12 +/- 7 months old. PA was measured via questionnaire at baseline and again at follow-up. Interviews regarding PA occurred at follow-up. RESULTS: PA significantly decreased in parents across the time period (P < .001), and parents attributed this decrease to having a child and being pregnant. Parents mentioned they lack time, energy, and motivation for PA as a result of caring for a new child. Parents who maintained their activity level stated they prioritized PA and chose activities they enjoyed. CONCLUSIONS: These results show that although activity levels decrease in individuals who have a child, PA in new parents may be a function of priority, intensity, and enjoyment. PMID- 25133321 TI - Synthesis, characterization, and swelling behaviors of salt-sensitive maize bran poly(acrylic acid) superabsorbent hydrogel. AB - A novel composite hydrogel was prepared via UV irradiation copolymerization of acrylic acid and maize bran (MB) in the presence of composite initiator (2,2 dimethoxy-2-phenylacetophenone and ammonium persulfate) and cross-linker (N,N' methylenebis(acrylamide)). Under the optimized conditions, maize bran poly(acrylic acid) was obtained (2507 g g(-1) in distilled water and 658 g g(-1) in 0.9 wt % NaCl solution). Effects of granularity, salt concentration, and various cations and anions on water absorbency were investigated. It was found that swelling was extremely sensitive to the ionic strength and cation and anion type. Swelling kinetics and water diffusion mechanism in distilled water were also discussed. Moreover, the product showed excellent water retention capability under the condition of high temperature or high pressure. The salt sensitivity, good water absorbency, and excellent water retention capability of the hydrogels give this intelligentized polymer wide potential applications. PMID- 25133319 TI - Anosognosia for hemiplegia: The contributory role of right inferior frontal gyrus. AB - OBJECTIVE: Awareness of motor functioning is most likely a complex process that requires integration of sensory-motor feedback to constantly update the system on the functioning of the limb during motor behavior. Using lesion mapping procedures and behavioral measures, the current study aimed to evaluate neural correlates of anosognosia for hemiplegia (AHP) in the acute stage (first 48 hr) of right hemisphere stroke. METHOD: Thirty-five individuals with right hemisphere stroke who presented to an urban medical center within 24 hr of symptom onset were included in the study. All 35 individuals had hemiplegia, and 8 of these individuals exhibited AHP. RESULTS: Fisher's exact test statistical map of lesion deficit association (range is between-log(p) 4 to 11) found maximal value of 10.9 located in pars orbitalis (Brodmann's Area 47; BA). In this selected location, 6 out of 8 patients with AHP had tissue abnormality, whereas none of the unaffected subjects had tissue abnormality in BA 47. Right BA 44/45 was also found to be lesioned more frequently in individuals with AHP (75%) than without AHP (11%). CONCLUSIONS: The current study findings provide preliminary support for unique involvement of the right inferior frontal gyrus (IFG), pars orbitalis (BA 47) in AHP. The current data suggest that frontal operculum may play a key role in awareness of limb functioning. PMID- 25133323 TI - Detection of low-concentration contaminants in solution by exploiting chemical derivatization in surface-enhanced Raman spectroscopy. AB - A simple derivatization methodology is shown to extend the application of surface enhanced Raman spectroscopy (SERS) to the detection of trace concentration of contaminants in liquid form. Normally in SERS the target analyte species is already present in the molecular form in which it is to be detected and is extracted from solution to occupy sites of enhanced electromagnetic field on the substrate by means of chemisorption or drop-casting and subsequent evaporation of the solvent. However, these methods are very ineffective for the detection of low concentrations of contaminant in liquid form because the target (ionic) species (a) exhibits extremely low occupancy of enhancing surface sites in the bulk liquid environment and (b) coevaporates with the solvent. In this study, the target analyte species (acid) is detected via its solid derivative (salt) offering very significant enhancement of the SERS signal because of preferential deposition of the salt at the enhancing surface but without loss of chemical discrimination. The detection of nitric acid and sulfuric acid is demonstrated down to 100 ppb via reaction with ammonium hydroxide to produce the corresponding ammonium salt. This yields an improvement of ~4 orders of magnitude in the low concentration detection limit compared with liquid phase detection. PMID- 25133322 TI - Electroporation-delivered fluorescent protein biosensors for probing molecular activities in cells without genetic encoding. AB - Fluorescent protein biosensors are typically implemented via genetic encoding which makes the examination of scarce cell samples impractical. By directly delivering the protein form of the biosensor into cells using electroporation, we detected intracellular molecular activity with the sample size down to ~100 cells with high spatiotemporal resolution. PMID- 25133324 TI - Health threat associated with Caucasian giant hogweeds: awareness among doctors and general public in Poland. AB - CONTEXT: The Caucasian giant hogweeds (Heracleum sosnowskyi and H. mantegazzianum) are aggressive invaders successfully spreading across different parts of Europe. Their sap containing linear furanocoumarins can lead to a persisting cutaneous dermatitis and massive skin necrosis. OBJECTIVE: We aimed to assess the awareness of the giant hogweeds' threat among physicians and general public in Poland. METHODS: The level of awareness was assessed using a short questionnaire given to different groups of physicians: dermatologists (DMs), general practitioners (GPs) and occupational practitioners (OPs). An independent questionnaire was also addressed to the general public. RESULTS: Among the surveyed physician groups, DMs were the best informed, while OPs were the worst informed on health threats associated with the giant hogweeds and treatment methods. Most frequently, application of topical corticosteroids was indicated as a successful method of treatment following the exposure to hogweeds. In the general public, awareness was relatively low with only 57.7% of the surveyed having ever heard about these plants. TV, press and Internet were among the most frequent sources of information in this regard. CONCLUSIONS: Public and medical attention needs to be raised as to the threats associated with giant hogweeds, particularly in countries that are highly infested with these plants. PMID- 25133325 TI - Infrared and Raman spectra, theoretical calculations, conformations, and two dimensional potential energy surface of 2-cyclopenten-1-one ethylene ketal. AB - The infrared and Raman spectra of the bicyclic spiro molecule 2-cyclopenten-1-one ethylene ketal (CEK) have been recorded. Density functional theory (DFT) calculations were used to compute the theoretical spectra, and these agree well with the experimental spectra. The structures and conformational energies for the two pairs of conformational minima, which can be defined in terms of ring-bending (x) and ring-twisting (tau) vibrational coordinates, have also been calculated. Utilizing the results from ab initio MP2/cc-PVTZ computations, a two-dimensional potential energy surface (PES) was calculated. The energy levels and wave functions for this PES were then calculated, and the characteristics of these were analyzed. At lower energies, all of the quantum states are doubly degenerate and correspond to either the lower-energy conformation L or to conformation H, which is 154 cm(-1) higher in energy. At energies above the barrier to interconversion of 264 cm(-1), the wave functions show that the quantum levels have significant probabilities for both conformations. PMID- 25133326 TI - Natural course vs interventions to clear common bile duct stones: data from the Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks). AB - IMPORTANCE: The optimal strategy for common bile duct stones (CBDSs) encountered during cholecystectomy is yet to be determined. OBJECTIVE: To evaluate the outcomes after various interventional techniques to clear the bile ducts and the natural course of CBDSs found during intraoperative cholangiography. DESIGN, SETTING, AND PARTICIPANTS: In a large retrospective cohort analysis, we analyzed data from the Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks). We included all patients with CBDSs found on intraoperative cholangiography during cholecystectomy from May 1, 2005, through December 31, 2009. EXPOSURES: Presence of CBDSs on intraoperative cholangiography. MAIN OUTCOMES AND MEASURES: Relation between strategies for handling CBDSs in terms of complication rates and/or incomplete clearance with need of intervention (ie, unfavorable outcomes). RESULTS: In 38,864 cholecystectomies, CBDSs were found in 3969 patients, of whom 3828 underwent analysis. Earlier or ongoing symptoms were more common with increasing stone size (P < .001). In total, postoperative unfavorable outcomes were found in 14.9% but less frequently for patients with smaller stones (P < .01). Among patients in whom no intraoperative measures were taken (representing natural course), the risk for unfavorable outcomes was 25.3%. This risk was significantly lower in patients in whom any measure was taken to clear the ducts (12.7%; odds ratio, 0.44 [95% CI, 0.35-0.55]). The same was found when small (<4 mm) and medium (4-8 mm) stones were analyzed separately (odds ratio, 0.52 [95% CI, 0.34-0.79] and 0.24 [95% CI, 0.17-0.32], respectively). CONCLUSIONS AND RELEVANCE: The high rates of unfavorable outcomes associated with taking no measures when CBDSs are found during cholecystectomy suggest that the natural course might not be as favorable as earlier suggested. This finding implies that, in general, efforts should be made to clear the bile ducts. PMID- 25133340 TI - Now available: wound care-related quality measures. PMID- 25133328 TI - Subcutaneous veltuzumab, a humanized anti-CD20 antibody, in the treatment of refractory pemphigus vulgaris. AB - IMPORTANCE B-cell depletion with the anti-CD20 antibody rituximab is highly effective for pemphigus vulgaris (PV) treatment. However,most patients experience relapse, and intravenous rituximab infusions are expensive. Therefore, cost effective anti-CD20 therapies are desirable.OBSERVATIONS A compassionate-use investigational new drug protocol was approved to administer veltuzumab, a second generation humanized anti-CD20 antibody, to a patient with refractory PV. Veltuzumab was administered as two 320-mg (188mg/m2) subcutaneous doses 2 weeks apart, resulting in complete remission of disease off therapy. The disease relapsed 2 years after treatment. A second cycle of subcutaneous veltuzumab, using the same dosage regimen, again induced complete remission off therapy, which remained at9 months. No serious adverse events occurred during 35 months of follow-up. Serum veltuzumab levels were 22 and 29 MUg/mL 2 weeks after the first dose of each cycle, and the drug remained detectable in the serum for longer than 3 months. Relapse and response to veltuzumab generally correlated with desmoglein 3 enzyme-linked immunosorbent assay index values. Shortly after a relapse that occurred after a long-term remission, the patient demonstrated an elevated naive (CD19+CD27-) to memory (CD19+CD27+) B-cell ratio of 19.5 and transitional (CD19+CD24+CD38+) B-cell frequency of 12.5%.CONCLUSIONS AND RELEVANCE Subcutaneous veltuzumab may be a safe, effective, and more economical alternative to intravenous rituximab for PV therapy. Clinical trials of subcutaneous veltuzumab for PV are warranted. PMID- 25133341 TI - Wounds in patients with HIV. AB - Highly active antiretroviral therapy has dramatically reduced morbidity and mortality among patients who are HIV-positive. A retrospective review of the authors' data separated subjects into cohorts based on HIV status and matched them for age and gender. The authors' data reveal a higher fraction of venous ulcers compared with a lower fraction of pressure ulcers in the seropositive population. PMID- 25133327 TI - Association between occupational exposure and lung function, respiratory symptoms, and high-resolution computed tomography imaging in COPDGene. AB - RATIONALE: Although occupational exposure to dust and fumes is considered a risk factor for chronic obstructive pulmonary disease, this determination has been limited by reliance on spirometry alone to assess disease severity in predominantly male populations. OBJECTIVES: To determine the effect of occupational exposure on lung function, respiratory symptoms, and findings of emphysema and airway wall thickness measured using quantitative computed tomography in men and women. METHODS: COPDGene is a multicenter study of current and former smokers that underwent standardized volumetric chest computed tomography scans to assess airways, % emphysema, and % gas trapping. Spirometry and a respiratory questionnaire including occupational history were also analyzed in 9,614 subjects (4,496 women). Logistic regression and analysis of covariance was used to assess associations with exposure. MEASUREMENTS AND MAIN RESULTS: Occupational exposure to both dust and fumes was reported by 47.9% of men and 20.1% of women. Adjusting for age, race, body mass index, education, and current and lifetime smoking, the odds ratios for persons with dust and fume exposures for chronic cough, chronic phlegm, persistent wheeze, and Global Initiative for Chronic Obstructive Lung Disease stages 2 and higher chronic obstructive pulmonary disease were significantly elevated and similar for men (1.83, 1.84, 2.0, 1.61, respectively) and women (1.65, 1.82, 1.98, 1.90, respectively). The % predicted FEV1 was similarly lower in those with exposure in men (70.7 +/- 0.8 vs. 76.0 +/- 0.9; P < 0.001) and women (70.5 +/- 0.8 vs. 77.2 +/- 0.8; P < 0.001). Percent emphysema and gas trapping was greater in those exposed to dust and fumes in men and women. In men, but not in women, persons with exposure had a greater mean square root wall area of 10-mm internal perimeter airways. CONCLUSIONS: Occupational exposure to dust and fumes in men and women is similarly associated with airflow obstruction, respiratory symptoms, more emphysema, and gas trapping in men and women. PMID- 25133342 TI - Excision, skin grafting, corticosteroids, adjuvant radiotherapy, pressure therapy, and emancipation: the ESCAPE model for successful taming of giant auricular keloids. AB - The authors treated 24 giant auricular keloids (mean size, 11 cm) from January 2008 to July 2012 using a novel protocol consisting of complete excision, skin grafting, a 1-time intraoperative injection of triamcinolone, immediate radiotherapy, and sustained pressure therapy. At 1 year, the success rate was 87.5%. PMID- 25133343 TI - The Pieper-Zulkowski pressure ulcer knowledge test. AB - OBJECTIVE: To describe the development and initial testing of the Pieper Zulkowski Pressure Ulcer Knowledge Test (PZ-PUKT). DESIGN: Cross-sectional, instrument testing. SETTING: Hospital association pressure ulcer educational program conference. METHODS: Pressure ulcer research and guidelines from the last 5 years were examined for test item content. The initial PZ-PUKT had 115 items; response options were "true," "false," and "don't know." Registered nurses (N = 108) were randomly divided into 2 groups to take either the 60 prevention/risk and staging items or the 55 wound description items. Analyses of these responses resulted in 72 items, which were administered in total to a second cohort of 98 nurses for reliability. RESULTS: Cronbach's alpha was .80 for the 72-item PZ PUKT. Cronbach's alpha values for the subscales were as follows: staging, .67; wound description, .64; and prevention/risk, .56. The mean correct scores were as follows: total, 80%; prevention, 77%; staging, 86%; and wound description, 77%. Nurses with wound care certification scored significantly higher on the PZ-PUKT than did nurses with other clinical certifications or with nurses who lacked certification. CONCLUSIONS: The PZ-PUKT has updated content about pressure ulcer prevention/risk, staging, and wound description. Reliability values are highest for the total test. Further use of the instrument in diverse settings will add to reliability testing and may provide direction for determination of a passing cutoff score. PMID- 25133344 TI - Arterial disease ulcers, part 1: clinical diagnosis and investigation. AB - Arterial disease (peripheral vascular disease) is the result of narrowing of the blood vessel lumen. The classic clinical signs need to be recognized early before progression to arterial predominant disease and limb ischemia. Arterial ulcers or tissue breakdown can result from trauma, infection, or other etiologies with diabetes, smoking, increasing age, and hypertension the most important risk factors. Diagnostic testing starts with a palpable pulse with special investigation including handheld Doppler for ankle brachial pressure index ratios, segmental duplex leg Doppler waveforms, and more specialized procedures, including transcutaneous oxygen saturation. PMID- 25133346 TI - Meaningful use audit checklist. PMID- 25133347 TI - Phytoextraction and dissipation of lindane by Spinacia oleracea L. AB - Remediation and management of organochlorine pesticide (OCPs) contaminated soil is becoming a global priority as they are listed in the Stockholm list of persistent organic pollutants (POPs) for global elimination. Lindane is a OCPs candidate recently included in the Stockholm list. However, India has an exemption to produce lindane for malaria control. Because of its widespread use during the last few decades, lindane contaminated soils are found in almost all parts of India. Since phytoremediation is widely acknowledged as an innovative strategy for the clean-up of contaminated soils; the present study was aimed to evaluate the phytoextraction and dissipation of lindane by a leafy vegetable Spinacia oleracea L (Spinach). The test plant was grown in different concentrations of lindane (5, 10, 15 and 20 mg kg(-1)) and harvested at 10, 30 and 45 days. At 45 days, the concentrations of lindane in root and leaf of Spinach growing in four different concentrations were reached up to 3.5, 5.4, 7.6 and 12.3 mg kg(-1) and 1.8, 2.2, 3 and 4.9 mg kg(-1), respectively. There was a significant difference (p<0.01) in the dissipation of lindane in vegetated and non-vegetated soil. Moreover, the residual lindane in four experiments was reduced to 81, 76, 69 and 61 percent, respectively. The experimental results indicate that Spinach can be used for the phytoremediation of lindane. However, more studies are required to prevent the toxicity of harvested parts. PMID- 25133348 TI - Antibiotic resistance monitoring in heterotrophic bacteria from anthropogenic polluted seawater and the intestines of oyster Crassostrea hongkongensis. AB - A total of 1,050 strains of heterotrophic bacteria isolated from farming seawater and the intestines of oyster species Crassostrea hongkongensis were tested for resistance to 10 antibiotics by the Kirby-Bauer diffusion method. The resistant rates of seawater-derived bacteria to chloramphenicol, enrofloxacin, and ciprofloxacin were low (less than 20%), whereas the bacteria obtained from oysters showed low resistance to chloramphenicol and enrofloxacin. Many strains showed high resistant rates (more than 40%) to furazolidone, penicillin G, and rifampin. A total of 285 strains from farming seawater and oysters were resistant to more than three antibiotics. Several strains showed resistance to more than nine antibiotics. Furthermore, the peak resistant rates of the seawater-derived strains to multiple antibiotics overlapped in April, June, September, and November, and those of oyster-derived strains overlapped during April, July, and September. The multi-resistant rate patterns of strains from farming seawater and oyster intestines were similar. PMID- 25133349 TI - An ethically appropriate strategy to combat obesity and food insecurity: the urban food initiative. PMID- 25133351 TI - Prognostic value of the Duke treadmill score in octogenarians undergoing myocardial perfusion imaging. AB - OBJECTIVES/BACKGROUND: Although Duke treadmill score (DTS) is the most widely used risk stratification method in younger patients undergoing exercise treadmill test (ETT) its specific value in the elderly is not established. METHODS: 137 patients aged >=80 years who underwent ETT myocardial perfusion imaging (MPI) were studied. DTS and MPI (including summed stress scores, SSS) related data were registered per patient and follow up was performed to document cardiac death (CD), myocardial infarction (MI) and late (>3 months) revascularization (LR). Kaplan Meir and Cox regression survival analysis were employed to determine the prognostic value of DTS in relation to MPI data for these endpoints. RESULTS: After a median follow up duration of 6.7 years 28 deaths, 7 CDs, 4 non fatal MIs and 12 LRs were observed. Incidence rates of CD/MI were significantly different only between low and high risk SSS categories (p = 0.044). Risk groups by DTS had no significant differences in survival free of CD/MI (p = 0.743) in contrast to risk groups according to SSS (p = 0.026), while both DTS and SSS based risk groups had significantly different survival free of CD/MI or LR. SSS was a significant univariate predictor of both CD/MI (HR 1.088, p = 0.019) and CD/MI or LR (HR 1.095, p < 0.001), but DTS only of the latter endpoint (HR 0.909, p = 0.003). CONCLUSIONS: In octogenarians DTS was found to be a significant predictor of the LR related endpoint but not of the hard endpoint of CD/MI, in contrast to SSS which was a powerful predictor of both soft and hard cardiac endpoints. PMID- 25133350 TI - Cartilage oligomeric matrix protein (COMP) in murine brachiocephalic and carotid atherosclerotic lesions. AB - OBJECTIVE: To investigate the hypothesis that COMP can influence the morphology, stability and size of murine atherosclerotic lesions. METHODS: ApoE- and ApoE/COMP-knockout mice were fed a high-fat diet to develop atherosclerotic plaques at lesion sites of three different types; inflammatory and fibrous plaques induced in the carotid artery by low or oscillatory shear stress, respectively, and spontaneously developing plaques in the brachiocephalic artery. The localization of COMP in the plaques and the effect of COMP deficiency on plaque development were evaluated. RESULTS: COMP immunoreactivity was observed in about half of the investigated plaques from the ApoE null mice, mainly located along the intima-medial border. There were no significant differences in the size of inflammatory and fibrous carotid plaques between the genotypes. Plaques in the brachiocephalic artery from ApoE mice lacking COMP were increased in size with 54%. In these plaques the collagen content was also increased by 48%. There were no differences in relative collagen content in inflammatory and fibrous carotid plaques between genotypes. Polarized light microscopy showed that the increase in total collagen in brachiocephalic plaques was more than proportionally accounted for by an increase in thicker collagen fibrils. CONCLUSION: We have shown that COMP deficiency has a significant impact on atherosclerotic plaque morphology and size. Our data also suggest that an altered collagen metabolism may be an important mechanism in this finding. PMID- 25133352 TI - Prognostic value of flow-mediated dilation in patients with systemic lupus erythematosus: a pilot prospective cohort study. AB - This pilot study evaluated the predictive value of flow-mediated dilation (FMD) for damage accrual in a cohort of SLE patients. Thirty-eight female SLE patients without cardiovascular involvement were enrolled. Clinical history, traditional cardiovascular risk factors, laboratory parameters, disease activity and damage and brachial artery FMD were collected at study entry and after a mean follow-up of 4.5 years. At enrollment, 18 patients (47%) presented active disease; mean FMD was 7.9 +/- 3.1%, with no statistically significant differences between women with active and inactive disease. During the follow-up, 3 patients died and 14 accrued organ damage. Baseline FMD did not predict death and damage accrual. FMD showed significant decline over time, which was greater in patients with poor outcome (-3.9% vs -1.9%, p = 0.03). In conclusion, in a cohort of SLE patients, baseline FMD was not predictive of damage accrual. However, the latter was associated with progressive loss of FMD. PMID- 25133353 TI - Occupational risk factors for low back pain among drivers of three-wheelers in Sri Lanka. AB - BACKGROUND: Approximately 5% of all households in Sri Lanka operate a three wheeler as their primary source of income. However, very little is known about the occupational health risks associated with driving these vehicles. OBJECTIVES: The aim of this study was to assess occupational risk factors, including the number of hours worked associated with the 4-week prevalence of low back pain (LBP) among drivers of three-wheelers. METHODS: Questionnaires were administered to 200 full-time drivers of three-wheelers from the Galle District in Sri Lanka. Occupational, psychological, socio-demographic, lifestyle, and anthropometric variables were collected. Univariate and multivariate analysis were used to investigate the correlation between occupational risk factors of the prevalence of LBP. RESULTS: 15.5% of respondents reported experiencing LBP in the previous 4 months. Univariate analysis revealed that the number of hours worked per week, feeling pressure to compete with other drivers, and perceived stress scale scores were significantly associated with the 4-week prevalence of LBP. Multivariate analysis found that the number of hours worked per week and engine type were significantly associated with LBP. CONCLUSIONS: LBP is common among drivers of three-wheelers in Sri Lanka. Long work hours and two-stroke engines were significantly associated with LBP. Results from this study point towards a role for educational, behavioral health, and policy interventions to help prevent and reduce LBP among these drivers. PMID- 25133354 TI - Structural stability of E. coli trigger factor studied by synchrotron small-angle X-ray scattering. AB - Solution small-angle X-ray scattering (SAXS) is an effective technique for quantitatively measuring the compactness and shape of proteins. We use SAXS to study the structural characteristics and unfolding transitions induced by urea for full length Escherichia coli trigger factor (TF) and a series of truncation mutants, obtaining and comparing the radiuses of gyration (Rg), the distance distribution function (P(r) function) and integrated intensity of TF variants in native and unfolding states. The C-terminal 72-residue truncated mutant TF360 exhibited dramatic structural differences and reduced stability compared with the whole TF molecule, while the N-domain truncated mutant MC maintained its compact structure with reduced stability. These results indicate that the C-terminal region of TF plays an important role in the structural and conformational stabilities of the TF molecule, while the N-domain is relatively independent. PMID- 25133355 TI - Exit interviews to reduce turnover amongst healthcare professionals. AB - BACKGROUND: Exit interviews are widely used in healthcare organisations to identify reasons for staff attrition, yet their usefulness in limiting turnover is unclear. OBJECTIVES: To determine the effectiveness of various exit interview strategies in decreasing turnover rates amongst healthcare professionals. SEARCH METHODS: We searched the Cochrane EPOC Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid (1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID (1806-) between October 31 and November 6, 2012. We also screened the reference lists of included studies and relevant reviews; and searched trial registries for planned and on-going studies. We did not restrict searches by language or publication date. SELECTION CRITERIA: Randomised controlled trials, controlled clinical trials, controlled before-after studies and interrupted time series studies comparing turnover rates between healthcare professionals who had undergone one form of exit interview with another form of exit interview or with no interview. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. MAIN RESULTS: The original search identified 1560 citations, of which we considered 19 potentially relevant. The two authors independently reviewed the abstracts of these studies and retrieved the full texts of eight studies. We excluded all eight following independent assessment; they were either interviews, commentaries on how to do an exit interview or descriptive studies about reasons for leaving. We found no studies that matched our inclusion criteria. For this first update, we screened 2220 citations and identified no new studies. AUTHORS' CONCLUSIONS: Evidence about the effectiveness of exit interviews to reduce turnover is currently not available. However, exit interviews may provide useful information about the work environment which, in turn, may be useful in the development of interventions to reduce turnover. PMID- 25133358 TI - Patients' understanding of their hospitalizations and association with satisfaction. PMID- 25133360 TI - Atypical antipsychotic drugs and the risk for acute kidney injury and other adverse outcomes in older adults: a population-based cohort study. AB - BACKGROUND: Several adverse outcomes attributed to atypical antipsychotic drugs, specifically quetiapine, risperidone, and olanzapine, are known to cause acute kidney injury (AKI). Such outcomes include hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis. OBJECTIVE: To investigate the risk for AKI and other adverse outcomes associated with use of atypical antipsychotic drugs versus nonuse. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, from 2003 to 2012. PATIENTS: Adults aged 65 years or older who received a new outpatient prescription for an oral atypical antipsychotic drug (n=97,777) matched 1:1 with those who did not receive such a prescription. MEASUREMENTS: The primary outcome was hospitalization with AKI (assessed by using a hospital diagnosis code and, in a subpopulation, serum creatinine levels) within 90 days of prescription for atypical antipsychotic drugs. RESULTS: Atypical antipsychotic drug use versus nonuse was associated with a higher risk for hospitalization with AKI (relative risk [RR], 1.73 [95% CI, 1.55 to 1.92]). This association was consistent when AKI was assessed in a subpopulation for which information on serum creatinine levels was available (5.46% vs. 3.34%; RR, 1.70 [CI, 1.22 to 2.38]; absolute risk increase, 2.12% [CI, 0.80% to 3.43%]). Drug use was also associated with hypotension (RR, 1.91 [CI, 1.60 to 2.28]), acute urinary retention (RR, 1.98 [CI, 1.63 to 2.40]), and all cause mortality (RR, 2.39 [CI, 2.28 to 2.50]). LIMITATION: Only older adults were included in the study. CONCLUSION: Atypical antipsychotic drug use is associated with an increased risk for AKI and other adverse outcomes that may explain the observed association with AKI. The findings support current safety concerns about the use of these drugs in older adults. PRIMARY FUNDING SOURCE: Academic Medical Organization of Southwestern Ontario. PMID- 25133359 TI - Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival analysis of the Cystic Fibrosis Foundation patient registry. AB - BACKGROUND: Advances in treatments for cystic fibrosis (CF) continue to extend survival. An updated estimate of survival is needed for better prognostication and to anticipate evolving adult care needs. OBJECTIVE: To characterize trends in CF survival between 2000 and 2010 and to project survival for children born and diagnosed with the disease in 2010. DESIGN: Registry-based study. SETTING: 110 Cystic Fibrosis Foundation-accredited care centers in the United States. PATIENTS: All patients represented in the Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2000 and 2010. MEASUREMENTS: Survival was modeled with respect to age, age at diagnosis, gender, race or ethnicity, F508del mutation status, and symptoms at diagnosis. RESULTS: Between 2000 and 2010, the number of patients in the CFFPR increased from 21,000 to 26,000, median age increased from 14.3 to 16.7 years, and adjusted mortality decreased by 1.8% per year (95% CI, 0.5% to 2.7%). Males had a 19% (CI, 13% to 24%) lower adjusted risk for death than females. Median survival of children born and diagnosed with CF in 2010 is projected to be 37 years (CI, 35 to 39 years) for females and 40 years (CI, 39 to 42 years) for males if mortality remains at 2010 levels and more than 50 years if mortality continues to decrease at the rate observed between 2000 and 2010. LIMITATIONS: The CFFPR does not include all patients with CF in the United States, and loss to follow-up and missing data were observed. Additional analyses to address these limitations suggest that the survival projections are conservative. CONCLUSION: Children born and diagnosed with CF in the United States in 2010 are expected to live longer than those born earlier. This has important implications for prognostic discussions and suggests that the health care system should anticipate greater numbers of adults with CF. PRIMARY FUNDING SOURCE: Cystic Fibrosis Foundation. PMID- 25133362 TI - Evidence-based risk communication: a systematic review. AB - BACKGROUND: Effective communication of risks and benefits to patients is critical for shared decision making. PURPOSE: To review the comparative effectiveness of methods of communicating probabilistic information to patients that maximize their cognitive and behavioral outcomes. DATA SOURCES: PubMed (1966 to March 2014) and CINAHL, EMBASE, and the Cochrane Central Register of Controlled Trials (1966 to December 2011) using several keywords and structured terms. STUDY SELECTION: Prospective or cross-sectional studies that recruited patients or healthy volunteers and compared any method of communicating probabilistic information with another method. DATA EXTRACTION: Two independent reviewers extracted study characteristics and assessed risk of bias. DATA SYNTHESIS: Eighty four articles, representing 91 unique studies, evaluated various methods of numerical and visual risk display across several risk scenarios and with diverse outcome measures. Studies showed that visual aids (icon arrays and bar graphs) improved patients' understanding and satisfaction. Presentations including absolute risk reductions were better than those including relative risk reductions for maximizing accuracy and seemed less likely than presentations with relative risk reductions to influence decisions to accept therapy. The presentation of numbers needed to treat reduced understanding. Comparative effects of presentations of frequencies (such as 1 in 5) versus event rates (percentages, such as 20%) were inconclusive. LIMITATION: Most studies were small and highly variable in terms of setting, context, and methods of administering interventions. CONCLUSION: Visual aids and absolute risk formats can improve patients' understanding of probabilistic information, whereas numbers needed to treat can lessen their understanding. Due to study heterogeneity, the superiority of any single method for conveying probabilistic information is not established, but there are several good options to help clinicians communicate with patients. PRIMARY FUNDING SOURCE: None. PMID- 25133363 TI - Cystic fibrosis: recent successes present new challenges. PMID- 25133364 TI - Inside special care. PMID- 25133365 TI - Aggregate cost of mammography screening in the United States. PMID- 25133366 TI - Aggregate cost of mammography screening in the United States. PMID- 25133367 TI - Aggregate cost of mammography screening in the United States. PMID- 25133368 TI - Prescription drug abuse. PMID- 25133369 TI - Prescription drug abuse. PMID- 25133370 TI - Prescription drug abuse. PMID- 25133371 TI - The dueling obligations of opioid stewardship. PMID- 25133372 TI - The dueling obligations of opioid stewardship. PMID- 25133375 TI - Summaries for patients. Improved survival of patients with cystic fibrosis. PMID- 25133376 TI - Web Exclusives. The consult guys--is that hemoglobin high enough? PMID- 25133377 TI - ACP Journal Club. Review: Natriuretic peptide-guided therapy reduces mortality more than clinically guided therapy in heart failure. PMID- 25133378 TI - ACP Journal Club. Review: Self-collected samples are less accurate for HPV testing than clinician-collected samples. PMID- 25133379 TI - ACP Journal Club. ACC/AHA Pooled Cohort Risk Equations predicted 5-y risk for CV events in adults considered for statin initiation. PMID- 25133380 TI - ACP Journal Club. ACC/AHA, Adult Treatment Panel III, and ESC guidelines overestimated risk for CVD in older adults. PMID- 25133381 TI - ACP Journal Club. Review: In diabetes, ACE-Is, but not ARBs, reduce mortality and major CV events compared with placebo or active treatment. PMID- 25133382 TI - ACP Journal Club. In uncontrolled type 2 diabetes, CBT improved glycemic control and reduced depression. PMID- 25133383 TI - ACP Journal Club. Bariatric surgery improved HbA1c more than intensive medical therapy in obese patients with uncontrolled type 2 DM. PMID- 25133384 TI - ACP Journal Club. In noncardiac surgery, perioperative aspirin did not reduce death or MI at 30 d but increased major bleeding. PMID- 25133385 TI - ACP Journal Club. Methotrexate reduced pain and improved function in symptomatic knee osteoarthritis. PMID- 25133386 TI - ACP Journal Club. In atrial fibrillation, dabigatran had similar efficacy to warfarin but caused less bleeding in higher GFR. PMID- 25133387 TI - ACP Journal Club. Review: In COPD, fluticasone or budesonide increases serious pneumonia but not mortality. PMID- 25133388 TI - ACP Journal Club. Review: Selective digestive decontamination reduces mortality more than chlorhexidine in general ICU patients. PMID- 25133390 TI - Nanoscale Diblock copolymer micelles: characterizations and estimation of the effective diffusion coefficients of biomolecules release through cylindrical diffusion model. AB - Biomolecules have been widely investigated as potential therapeutics for various diseases. However their use is limited due to rapid degradation and poor cellular uptake in vitro and in vivo. To address this issue, we synthesized a new nano carrier system comprising of cholic acid-polyethylenimine (CA-PEI) copolymer micelles, via carbodiimide-mediated coupling for the efficient delivery of small interfering ribonucleic acid (siRNA) and bovine serum albumin (BSA) as model protein. The mean particle size of siRNA- or BSA-loaded CA-PEI micelles ranged from 100-150 nm, with zeta potentials of +3-+11 mV, respectively. Atomic force, transmission electron and field emission scanning electron microscopy demonstrated that the micelles exhibited excellent spherical morphology. No significant morphology or size changes were observed in the CA-PEI micelles after siRNA and BSA loading. CA-PEI micelles exhibited sustained release profile, the effective diffusion coefficients were successfully estimated using a mathematically-derived cylindrical diffusion model and the release data of siRNA and BSA closely fitted into this model. High siRNA and BSA binding and loading efficiencies (95% and 70%, respectively) were observed for CA-PEI micelles. Stability studies demonstrated that siRNA and BSA integrity was maintained after loading and release. The CA-PEI micelles were non cytotoxic to V79 and DLD-1 cells, as shown by alamarBlue and LIVE/DEAD cell viability assays. RT-PCR study revealed that siRNA-loaded CA-PEI micelles suppressed the mRNA for ABCB1 gene. These results revealed the promising potential of CA-PEI micelles as a stable, safe, and versatile nano-carrier for siRNA and the model protein delivery. PMID- 25133389 TI - Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine. AB - BACKGROUND: One promising new Artemisinin-based combination therapies (ACTs) is dihydroartemisinin-piperaquine (DHA-PQ). However, the pharmacokinetics of piperaquine and the relationship between drug levels and clinical efficacy are incompletely characterized, particularly in children. METHODS: We performed a single-arm open-label trial in Bobo-Dioulasso, Burkina Faso. A total of 379 participants aged 6 months or more with uncomplicated falciparum malaria were enrolled. Each participant received daily dose of DHA-PQ for three days and followed for 42 days. Parasitological efficacy was analyzed, considering rates of recrudescence and overall recurrence. PK was an exploratory endpoint and a priori, no sample size had been determined. Day 7 capillary and venous plasma concentrations of piperaquine were measured in children aged 2-10 years. RESULTS: Of the 379 participants, 365 (96.3%) completed 42 days of follow-up. The median daily dose of PQ was 18.5 mg/kg [6.5-24]. Treatment with DHA-PQ was well tolerated with fever and parasitemia resolution within 48 hours in nearly all children. Recurrent malaria within 42 days of follow-up occurred in 31.3% (10/34) of children less than 2 years old, 16.0% (16/106) of those aged 2-5 years, 9.4% (15/160) of those aged 5-10 years, and none (0/68) of those over 10 years old. After genotyping, 3 of 41 recurrent episodes were recrudescence. An exploratory analysis shows that children with successful treatment outcomes had significantly higher median plasma concentrations of PQ compared to those with recurrent malaria within 42 days after therapy, considering either capillary samples (68 ng/ml [50-85] compared to 48 ng/ml [36-55], p<0.001) or venous samples (42 ng/ml [29-59] compared to 25 ng/ml [19-44], p<0.001). CONCLUSION: DHA-PQ was effective for uncomplicated P. falciparum malaria treatment and offers an alternative to other ACTs. Recurrent malaria was mainly due to new infections after treatment and was correlated with low day 7 PQ concentration in the youngest patients. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN59761234. PMID- 25133391 TI - A rank-based sequence aligner with applications in phylogenetic analysis. AB - Recent tools for aligning short DNA reads have been designed to optimize the trade-off between correctness and speed. This paper introduces a method for assigning a set of short DNA reads to a reference genome, under Local Rank Distance (LRD). The rank-based aligner proposed in this work aims to improve correctness over speed. However, some indexing strategies to speed up the aligner are also investigated. The LRD aligner is improved in terms of speed by storing [Formula: see text]-mer positions in a hash table for each read. Another improvement, that produces an approximate LRD aligner, is to consider only the positions in the reference that are likely to represent a good positional match of the read. The proposed aligner is evaluated and compared to other state of the art alignment tools in several experiments. A set of experiments are conducted to determine the precision and the recall of the proposed aligner, in the presence of contaminated reads. In another set of experiments, the proposed aligner is used to find the order, the family, or the species of a new (or unknown) organism, given only a set of short Next-Generation Sequencing DNA reads. The empirical results show that the aligner proposed in this work is highly accurate from a biological point of view. Compared to the other evaluated tools, the LRD aligner has the important advantage of being very accurate even for a very low base coverage. Thus, the LRD aligner can be considered as a good alternative to standard alignment tools, especially when the accuracy of the aligner is of high importance. Source code and UNIX binaries of the aligner are freely available for future development and use at http://lrd.herokuapp.com/aligners. The software is implemented in C++ and Java, being supported on UNIX and MS Windows. PMID- 25133393 TI - MiR-152 may silence translation of CaMK II and induce spontaneous immune tolerance in mouse liver transplantation. AB - Spontaneous immune tolerance in mouse liver transplantation has always been a hotspot in transplantation-immune research. Recent studies revealed that regulatory T cells (Tregs), hepatic satellite cells and Kupffer cells play a potential role in spontaneous immune tolerance, however the precise mechanism of spontaneous immune tolerance is still undefined. By using Microarray Chips, we investigated different immune regulatory factors to decipher critical mechanisms of spontaneous tolerance after mouse liver transplantation. Allogeneic (C57BL/6 C3H) and syngeneic (C3H-C3H) liver transplantation were performed by 6-8 weeks old male C57BL/6 and C3H mice. Graft samples (N = 4 each group) were collected from 8 weeks post-operation mice. 11 differentially expressed miRNAs in allogeneic grafts (Allografts) vs. syngeneic grafts (Syngrafts) were identified using Agilent Mouse miRNA Chips. It was revealed that 185 genes were modified by the 11 miRNAs, furthermore, within the 185 target genes, 11 of them were tightly correlated with immune regulation after Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Genbank data cross-comparison. Verified by real-time PCR and western blot, our results indicated that mRNA expression levels of IL-6 and TAB2 were respectively down regulated following miR-142-3p and miR 155 augment. In addition, increased miR-152 just silenced mRNA of CaMK II and down-regulated translation of CaMK II in tolerated liver grafts, which may play a critical role in immune regulation and spontaneous tolerance induction of mouse liver transplantation. PMID- 25133392 TI - Pyridostigmine restores cardiac autonomic balance after small myocardial infarction in mice. AB - The effect of pyridostigmine (PYR)--an acetylcholinesterase inhibitor--on hemodynamics and cardiac autonomic control, was never studied in conscious myocardial infarcted mice. Telemetry transmitters were implanted into the carotid artery under isoflurane anesthesia. Seven to ten days after recovery from the surgery, basal arterial pressure and heart rate were recorded, while parasympathetic and sympathetic tone (DeltaHR) was evaluated by means of methyl atropine and propranolol. After the basal hemodynamic recording the mice were subjected to left coronary artery ligation for producing myocardial infarction (MI), or sham operation, and implantation of minipumps filled with PYR or saline. Separate groups of anesthetized (isoflurane) mice previously (4 weeks) subjected to MI, or sham coronary artery ligation, were submitted to cardiac function examination. The mice exhibited an infarct length of approximately 12%, no change in arterial pressure and increased heart rate only in the 1st week after MI. Vagal tone decreased in the 1st week, while the sympathetic tone was increased in the 1st and 4th week after MI. PYR prevented the increase in heart rate but did not affect the arterial pressure. Moreover, PYR prevented the increase in sympathetic tone throughout the 4 weeks. Concerning the parasympathetic tone, PYR not only impaired its attenuation in the 1st week, but enhanced it in the 4th week. MI decreased ejection fraction and increased diastolic and systolic volume. Therefore, the pharmacological increase of peripheral acetylcholine availability by means of PYR prevented tachycardia, increased parasympathetic and decreased sympathetic tone after MI in mice. PMID- 25133394 TI - Characterisation of SalRAB a salicylic acid inducible positively regulated efflux system of Rhizobium leguminosarum bv viciae 3841. AB - Salicylic acid is an important signalling molecule in plant-microbe defence and symbiosis. We analysed the transcriptional responses of the nitrogen fixing plant symbiont, Rhizobium leguminosarum bv viciae 3841 to salicylic acid. Two MFS-type multicomponent efflux systems were induced in response to salicylic acid, rmrAB and the hitherto undescribed system salRAB. Based on sequence similarity salA and salB encode a membrane fusion and inner membrane protein respectively. salAB are positively regulated by the LysR regulator SalR. Disruption of salA significantly increased the sensitivity of the mutant to salicylic acid, while disruption of rmrA did not. A salA/rmrA double mutation did not have increased sensitivity relative to the salA mutant. Pea plants nodulated by salA or rmrA strains did not have altered nodule number or nitrogen fixation rates, consistent with weak expression of salA in the rhizosphere and in nodule bacteria. However, BLAST analysis revealed seventeen putative efflux systems in Rlv3841 and several of these were highly differentially expressed during rhizosphere colonisation, host infection and bacteroid differentiation. This suggests they have an integral role in symbiosis with host plants. PMID- 25133395 TI - Cost of disorders of the brain in Spain. AB - BACKGROUND: Brain disorders represent a high burden in Europe and worldwide. The objective of this study was to provide specific estimates of the economic costs of brain disorders in Spain, based on published epidemiological and economic evidence. METHODS: A cost-of-illness study with a societal perspective of 19 brain disorders was carried out. Cost data published between 2004 and 2012 was obtained from a systematic literature review. Direct healthcare, direct non medical and indirect costs were considered, prioritizing bottom-up information. All costs were converted to Euro and to year 2010. The missing values were imputed with European estimates. Sensitivity analyses based on qualitative assessment of the literature and on a Monte Carlo simulation were performed. RESULTS: The review identified 33 articles with information on costs for 11 disorders (8 neurological, 3 mental). The average per-patient cost ranged from 36,946 ? for multiple sclerosis to 402 ? for headache. The societal cost of the 19 brain disorders in Spain in 2010 was estimated in 84 ? billion. Societal costs ranged from 15 ? billion for dementia to 65 ? million for eating disorders. Mental disorders societal cost were 46 ? billions (55% of the total), while neurological disorder added up to 38 ? billion. Healthcare costs represented 37% of the societal costs of brain disorders, whereas direct non-medical constituted 29% and indirect costs 33%. CONCLUSION: Brain disorders have a substantial economic impact in Spain (equivalent to almost 8% of the country's GDP). Economic data on several important brain disorders, specially mental disorders, is still sparse. PMID- 25133396 TI - Differential modulation by IL-17A of Cholangitis versus Colitis in IL-2Ralpha deleted mice. AB - IFN-gamma is a signature Th1 cell associated cytokine critical for the inflammatory response in autoimmunity with both pro-inflammatory and potentially protective functions. IL-17A is the hallmark of T helper 17 (Th17) cell subsets, produced by gammadeltaT, CD8+ T, NK and NKT cells. We have taken advantage of our colony of IL-2Ralpha-/- mice that spontaneously develop both autoimmune cholangitis and inflammatory bowel disease. In this model CD8+ T cells mediate biliary ductular damage, whereas CD4+ T cells mediate induction of colon-specific autoimmunity. Importantly, IL-2Ralpha-/- mice have high levels of interferon gamma (IFN-gamma), and interleukin-17A (IL-17A). We produced unique double deletions of mice that were either IL-17A-/-IL-2Ralpha-/- or IFN-gamma-/-IL 2Ralpha-/- to specifically address the precise role of these two cytokines in the natural history of autoimmune cholangitis and colitis. Of note, deletion of IL 17A in IL-2Ralpha-/- mice led to more severe liver inflammation, but ameliorated colitis. In contrast, there were no significant changes in the immunopathology of double knock-out IFN-gamma-/- IL-2Ralpha-/- mice, compared to single knock-out IL 2Ralpha-/- mice with respect to cholangitis or colitis. Furthermore, there was a significant increase in pathogenetic CD8+ T cells in the liver of IL-17A-/-IL 2Ralpha-/- mice. Our data suggest that while IL-17A plays a protective role in autoimmune cholangitis, it has a pro-inflammatory role in inflammatory bowel disease. These data take on particular significance in the potential use of anti IL-17A therapy in humans with primary biliary cirrhosis. PMID- 25133397 TI - Operative rigid bronchoscopy: indications, basic techniques and results. AB - Palliative airway treatments are essential to improve quality and length of life in lung cancer patients with central airway obstruction. Rigid bronchoscopy has proved to be an excellent tool to provide airway access and control in this cohort of patients. The main indication for rigid bronchoscopy in adult bronchology remains central airway obstruction due to neoplastic or non neoplastic disease. We routinely use negative pressure ventilation (NPV) under general anaesthesia to prevent intraoperative apnoea and respiratory acidosis. This procedure allows opioid sparing, a shorter recovery time and avoids manually assisted ventilation, thereby reducing the amount of oxygen needed, while maintaining optimal surgical conditions. The major indication for NPV rigid bronchoscopy at our institution has been airway obstruction by neoplastic tracheobronchial tissue, mainly treated by laser-assisted mechanical dissection. When strictly necessary, we use silicone stents for neoplastic or cicatricial strictures, reserving metal stents to cover tracheo-oesophageal fistulae. NPV rigid bronchoscopy is an excellent tool for the endoscopic treatment of locally advanced tumours of the lung, especially when patients have exhausted the conventional therapeutic resources. Laser-assisted mechanical resection and stent placement are the most effective procedures for preserving quality of life in patients with advanced stage cancer. PMID- 25133400 TI - Proteomics-identified Bvg-activated autotransporters protect against bordetella pertussis in a mouse model. AB - Pertussis is a highly infectious respiratory disease of humans caused by the bacterium Bordetella pertussis. Despite high vaccination coverage, pertussis has re-emerged globally. Causes for the re-emergence of pertussis include limited duration of protection conferred by acellular pertussis vaccines (aP) and pathogen adaptation. Pathogen adaptations involve antigenic divergence with vaccine strains, the emergence of strains which show enhanced in vitro expression of a number of virulence-associated genes and of strains that do not express pertactin, an important aP component. Clearly, the identification of more effective B. pertussis vaccine antigens is of utmost importance. To identify novel antigens, we used proteomics to identify B. pertussis proteins regulated by the master virulence regulatory system BvgAS in vitro. Five candidates proteins were selected and it was confirmed that they were also expressed in the lungs of naive mice seven days after infection. The five proteins were expressed in recombinant form, adjuvanted with alum and used to immunize mice as stand-alone antigens. Subsequent respiratory challenge showed that immunization with the autotransporters Vag8 and SphB1 significantly reduced bacterial load in the lungs. Whilst these antigens induced strong opsonizing antibody responses, we found that none of the tested alum-adjuvanted vaccines - including a three component aP - reduced bacterial load in the nasopharynx, suggesting that alternative immunological responses may be required for efficient bacterial clearance from the nasopharynx. PMID- 25133401 TI - Antioxidant and antiproliferative activities of twenty-four Vitis vinifera grapes. AB - Grapes are rich in phytochemicals with many proven health benefits. Phenolic profiles, antioxidant and antiproliferative activities of twenty-four selected Vitis vinifera grape cultivars were investigated in this study. Large ranges of variation were found in these cultivars for the contents of total phenolics (95.3 to 686.5 mg/100 g) and flavonoids (94.7 to 1055 mg/100 g) and antioxidant activities (oxygen radical absorbance capacity 378.7 to 3386.0 mg of Trolox equivalents/100 g and peroxylradical scavenging capacity14.2 to 557 mg of vitamin C equivalents/100 g), cellular antioxidant activities (3.9 to 139.9 umol of quercetin equivalents/100 g without PBS wash and 1.4 to 95.8 umol of quercetin equivalents /100 g with PBS wash) and antiproliferative activities (25 to 82% at the concentrations of 100 mg/mL extracts).The total antioxidant activities were significantly correlated with the total phenolics and flavonoids. However, no significant correlations were found between antiproliferative activities and total phenolics or total flavonoids content. Wine grapes and color grapes showed much higher levels of phytochemicals and antioxidant activities than table grapes and green/yellow grapes. Several germplasm accessions with much high contents of phenolics and flavonoids, and total antioxidant activity were identified. These germplasm can be valuable sources of genes for breeding grape cultivars with better nutritional qualities of wine and table grapes in the future. PMID- 25133402 TI - Comparative proteomics of milk fat globule membrane proteins from transgenic cloned cattle. AB - The use of transgenic livestock is providing new methods for obtaining pharmaceutically useful proteins. However, the protein expression profiles of the transgenic animals, including expression of milk fat globule membrane (MFGM) proteins, have not been well characterized. In this study, we compared the MFGM protein expression profile of the colostrum and mature milk from three lines of transgenic cloned (TC) cattle, i.e., expressing recombinant human alpha lactalbumin (TC-LA), lactoferrin (TC-LF) or lysozyme (TC-LZ) in the mammary gland, with those from cloned non-transgenic (C) and conventionally bred normal animals (N). We identified 1, 225 proteins in milk MFGM, 166 of which were specifically expressed only in the TC-LA group, 265 only in the TC-LF group, and 184 only in the TC-LZ group. There were 43 proteins expressed only in the transgenic cloned animals, but the concentrations of these proteins were below the detection limit of silver staining. Functional analysis also showed that the 43 proteins had no obvious influence on the bovine mammary gland. Quantitative comparison revealed that MFGM proteins were up- or down-regulated more than twofold in the TC and C groups compared to N group: 126 in colostrum and 77 in mature milk of the TC-LA group; 157 in colostrum and 222 in mature milk of the TC LF group; 49 in colostrum and 98 in mature milk of the TC-LZ group; 98 in colostrum and 132 in mature milk in the C group. These up- and down-regulated proteins in the transgenic animals were not associated with a particular biological function or pathway, which appears that expression of certain exogenous proteins has no general deleterious effects on the cattle mammary gland. PMID- 25133403 TI - Hydrocortisone fails to abolish NF-kappaB1 protein nuclear translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG) and is associated with increased 30-day mortality in septic shock. AB - BACKGROUND: Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription factor nuclear-factor-kappaB (NF-kappaB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-kappaB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-kappaB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. METHODS: Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 ugml-1 LPS +/- hydrocortisone (10-5M), and NF-kappaB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. RESULTS: Hydrocortisone inhibited LPS induced nuclear translocation of NF-kappaB1 in II (25%+/-11;p = 0.0001) but not in DD genotypes (51%+/-15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. CONCLUSION: Hydrocortisone fails to inhibit LPS induced nuclear NF-kappaB1 translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG). In septic shock, hydrocortisone treatment is associated with markedly increased 30-day-mortality only in such carriers. Accordingly, previous heterogeneous results regarding the benefit of hydrocortisone in septic shock may be reconciled by genetic variation of the NFKB1 promoter polymorphism. PMID- 25133404 TI - Distinctly different dynamics and kinetics of two steroid receptors at the same response elements in living cells. AB - Closely related transcription factors (TFs) can bind to the same response elements (REs) with similar affinities and activate transcription. However, it is unknown whether transcription is similarly orchestrated by different TFs bound at the same RE. Here we have compared the recovery half time (t1/2), binding site occupancy and the resulting temporal changes in transcription upon binding of two closely related steroid receptors, the androgen and glucocorticoid receptors (AR and GR), to their common hormone REs (HREs). We show that there are significant differences at all of these levels between AR and GR at the MMTV HRE when activated by their ligands. These data show that two TFs bound at the same RE can have significantly different modes of action that can affect their responses to environmental cues. PMID- 25133407 TI - Identification of Trueperella pyogenes isolated from bovine mastitis by Fourier transform infrared spectroscopy. AB - The present study was designed to investigate the potential of Fourier transform infrared (FT-IR) spectroscopy to identify Trueperella (T.) pyogenes isolated from bovine clinical mastitis. FT-IR spectroscopy was applied to 57 isolates obtained from 55 cows in a period from 2009 to 2012. Prior to FT-IR spectroscopy these isolates were identified by phenotypic and genotypic properties, also including the determination of seven potential virulence factor encoding genes. The FT-IR analysis revealed a reliable identification of all 57 isolates as T. pyogenes and a clear separation of this species from the other species of genus Trueperella and from species of genus Arcanobacterium and Actinomyces. The results showed that all 57 isolates were assigned to the correct species indicating that FT-IR spectroscopy could also be efficiently used for identification of this bacterial pathogen. PMID- 25133408 TI - Workplace discrimination predicting racial/ethnic socialization across African American, Latino, and Chinese families. AB - Informed by Kohn and Schooler's (1969) occupational socialization framework, this study examined linkages between racial/ethnic minority mothers' perceptions of racial/ethnic discrimination in the workplace and adolescents' accounts of racial/ethnic socialization in the home. Data were collected from 100 mother early adolescent dyads who participated in a longitudinal study of urban adolescents' development in the Northeastern United States, including African American, Latino, and Chinese families. Mothers and adolescents completed surveys separately. We found that when mothers reported more frequent institutional discrimination at work, adolescents reported more frequent preparation for bias messages at home, across racial/ethnic groups. Mothers' experiences of interpersonal prejudice at work were associated with more frequent cultural socialization messages among African American and Latino families. Chinese youth reported fewer cultural socialization messages when mothers perceived more frequent interpersonal prejudice at work. Findings are discussed in the context of minority groups' distinct social histories and economic status in the United States. PMID- 25133409 TI - Selective incivility: immigrant groups experience subtle workplace discrimination at different rates. AB - Immigrants play an increasingly important role in local labor markets. Not only do they grow steadily in number but also in cultural, educational, and skill diversity, underlining the necessity to distinguish between immigrant groups when studying discrimination against immigrants. We examined immigrant employees' subtle discrimination experiences in a representative sample in Switzerland, controlling for dispositional influences. Results showed that mainly members of highly competitive immigrant groups, from immediate neighbor countries, experienced workplace incivility and that these incivility experiences were related to higher likelihoods of perceived discrimination at work. This research confirms recent accounts that successful but disliked groups are particularly likely to experience subtle interpersonal discrimination. PMID- 25133410 TI - The acculturation gap-distress model: Extensions and application to Arab Canadian families. AB - Using a multidomain and bidimensional approach, the present study applied and extended the acculturation gap-distress model with an immigrant Arab Canadian sample. Consistent with this model, immigrant Arab emerging adults (n = 113) perceived acculturation gaps between themselves and their parents with respect to their heritage and settlement culture orientation and values. Some of these gaps, in turn, were associated with poorer outcomes. Extending the model, the most problematic acculturation gaps were those in which the emerging adult perceived themselves to be more oriented to Arab culture and values than their parents. We also found some support for the moderating role of parent-emerging adult relationships. PMID- 25133405 TI - Cardiac sympathetic denervation in 6-OHDA-treated nonhuman primates. AB - Cardiac sympathetic neurodegeneration and dysautonomia affect patients with sporadic and familial Parkinson's disease (PD) and are currently proposed as prodromal signs of PD. We have recently developed a nonhuman primate model of cardiac dysautonomia by iv 6-hydroxydopamine (6-OHDA). Our in vivo findings included decreased cardiac uptake of a sympathetic radioligand and circulating catecholamines; here we report the postmortem characterization of the model. Ten adult rhesus monkeys (5-17 yrs old) were used in this study. Five animals received 6-OHDA (50 mg/kg i.v.) and five were age-matched controls. Three months post-neurotoxin the animals were euthanized; hearts and adrenal glands were processed for immunohistochemistry. Quantification of immunoreactivity (ir) of stainings was performed by an investigator blind to the treatment group using NIH ImageJ software (for cardiac bundles and adrenals, area above threshold and optical density) and MBF StereoInvestigator (for cardiac fibers, area fraction fractionator probe). Sympathetic cardiac nerve bundle analysis and fiber area density showed a significant reduction in global cardiac tyrosine hydroxylase-ir (TH; catecholaminergic marker) in 6-OHDA animals compared to controls. Quantification of protein gene protein 9.5 (pan-neuronal marker) positive cardiac fibers showed a significant deficit in 6-OHDA monkeys compared to controls and correlated with TH-ir fiber area. Semi-quantitative evaluation of human leukocyte antigen-ir (inflammatory marker) and nitrotyrosine-ir (oxidative stress marker) did not show significant changes 3 months post-neurotoxin. Cardiac nerve bundle alpha-synuclein-ir (presynaptic protein) was reduced (trend) in 6-OHDA treated monkeys; insoluble proteinase-K resistant alpha-synuclein (typical of PD pathology) was not observed. In the adrenal medulla, 6-OHDA monkeys had significantly reduced TH-ir and aminoacid decarboxylase-ir. Our results confirm that systemic 6-OHDA dosing to nonhuman primates induces cardiac sympathetic neurodegeneration and loss of catecholaminergic enzymes in the adrenal medulla, and suggests that this model can be used as a platform to evaluate disease modifying strategies aiming to induce peripheral neuroprotection. PMID- 25133411 TI - Identity threat at work: how social identity threat and situational cues contribute to racial and ethnic disparities in the workplace. AB - Significant disparities remain between racial and ethnic minorities' and Whites' experiences of American workplaces. Traditional prejudice and discrimination approaches explain these gaps in hiring, promotion, satisfaction, and well-being by pointing to the prejudice of people within organizations such as peers, managers, and executives. Grounded in social identity threat theory, this theoretical review instead argues that particular situational cues-often communicated by well-meaning, largely unprejudiced employees and managers-signal to stigmatized groups whether their identity is threatened and devalued or respected and affirmed. First, we provide an overview of how identity threat shapes the psychological processes of racial and ethnic minorities by heightening vigilance to certain situational cues in the workplace. Next, we outline several of these cues and their role in creating and sustaining perceptions of identity threat (or safety). Finally, we provide empirically grounded suggestions that organizations may use to increase identity safety among their employees of color. Taken together, the research demonstrates how situational cues contribute to disparate psychological experiences for racial and ethnic minorities at work, and suggests that by altering threatening cues, organizations may create more equitable, respectful, and inclusive environments where all people may thrive. PMID- 25133412 TI - Chinese American immigrant parents' emotional expression in the family: Relations with parents' cultural orientations and children's emotion-related regulation. AB - The present study examined 2 measures of Chinese American immigrant parents' emotional expression in the family context: self-reported emotional expressivity and observed emotional expression during a parent-child interaction task. Path analyses were conducted to examine the concurrent associations between measures of emotional expression and (a) parents' American and Chinese cultural orientations in language proficiency, media use, and social affiliation domains, and (b) parents' and teachers' ratings of children's emotion-related regulation. Results suggested that cultural orientations were primarily associated with parents' self-reported expressivity (rather than observed emotional expression), such that higher American orientations were generally associated with higher expressivity. Although parents' self-reported expressivity was only related to their own reports of children's regulation, parents' observed emotional expression was related to both parents' and teachers' reports of children's regulation. These results suggest that self-reported expressivity and observed emotional expression reflect different constructs and have differential relations to parents' cultural orientations and children's regulation. PMID- 25133413 TI - A randomized controlled trial to promote volunteering in older adults. AB - Volunteering is presumed to confer health benefits, but interventions to encourage older adults to volunteer are sparse. Therefore, a randomized controlled trial with 280 community-dwelling older German adults was conducted to test the effects of a theory-based social-cognitive intervention against a passive waiting-list control group and an active control intervention designed to motivate physical activity. Self-reports of weekly volunteering minutes were assessed at baseline (5 weeks before the intervention) as well as 2 and 6 weeks after the intervention. Participants in the treatment group increased their weekly volunteering minutes to a greater extent than participants in the control groups 6 weeks after the intervention. We conclude that a single, face-to-face group session can increase volunteering among older community-dwelling adults. However, the effects need some time to unfold because changes in volunteering were not apparent 2 weeks after the intervention. PMID- 25133415 TI - Longitudinal associations between activity and cognition vary by age, activity type, and cognitive domain. AB - The demonstration of correlated change is critical to understanding the relationship between activity engagement and cognitive functioning in older adulthood. Changes in activity have been shown to be related to changes in cognition, but little attention has been devoted to how this relationship may vary between specific activity types, cognitive domains, and age groups. Participants initially aged 65-98 years (M = 77.46 years) from the Australian Longitudinal Study of Ageing (n = 1,321) completed measurements of activity (i.e., cognitive, group social, one-on-one social, and physical) and cognition (i.e., perceptual speed, and immediate and delayed episodic memory) at baseline, 2, 8, 11, and 15 years later. Bivariate latent growth curve models covarying for education, sex, and baseline age and medical conditions revealed multiple positive-level relations between activity and cognitive performance, but activity level was not related to later cognitive change. Change in perceptual speed over 15 years was positively associated with change in cognitive activity, and change in immediate episodic memory was positively associated with change in one-on-one social activity. Old-old adults showed a stronger change-change covariance for mentally stimulating activity in relation to perceptual speed than did young-old adults. The differentiation by activity type, cognitive domain, and age contributes to the growing evidence that there is variation in the way cognitive ability at different ages is related to activity. PMID- 25133414 TI - Why does placement of persons with Alzheimer's disease into long-term care improve caregivers' well-being? Examination of psychological mediators. AB - Caregiving for individuals with Alzheimer's disease is associated with chronic stress and elevated symptoms of depression. Placement of the care receiver (CR) into a long-term care setting may be associated with improved caregiver well being; however, the psychological mechanisms underlying this relationship are unclear. This study evaluated whether decreases in activity restriction and increases in personal mastery mediated placement-related reductions in caregiver depressive symptoms. In a 5-year longitudinal study of 126 spousal Alzheimer's disease caregivers, we used multilevel models to evaluate placement-related changes in depressive symptoms (short form of the Center for Epidemiologic Studies Depression scale), activity restriction (Activity Restriction Scale), and personal mastery (Pearlin Mastery Scale) in 44 caregivers who placed their spouses into long-term care relative to caregivers who never placed their CRs. The Monte Carlo method for assessing mediation was used to evaluate the significance of the indirect effect of activity restriction and personal mastery on postplacement changes in depressive symptoms. Placement of the CR was associated with significant reductions in depressive symptoms and activity restriction and was also associated with increased personal mastery. Lower activity restriction and higher personal mastery were associated with reduced depressive symptoms. Furthermore, both variables significantly mediated the effect of placement on depressive symptoms. Placement-related reductions in activity restriction and increases in personal mastery are important psychological factors that help explain postplacement reductions in depressive symptoms. The implications for clinical care provided to caregivers are discussed. PMID- 25133416 TI - Aerobic Fitness Indices of Children Differed Not by Body Weight Status but by Level of Engagement in Physical Activity. AB - BACKGROUND: Moderate-to-vigorous physical activity (MVPA) improves aerobic fitness in children, which is usually assessed by maximal oxygen consumption. However, other indices of aerobic fitness have been understudied. OBJECTIVE: To compare net oxygen (VO2net), net energy consumption (Enet), net mechanical efficiency (MEnet), and lipid oxidation rate in active and inactive children across body weight statuses. DESIGN: The sample included normal-weight, overweight, and obese children of whom 44 are active (>=30 min of MVPA/d) and 41 are inactive (<30 min of MVPA/d). VO2net, Enet, MEnet and lipid oxidation rate were determined during an incremental maximal cycling test. RESULTS: Active obese participants had significantly lower values of VO2net and Enet and higher MEnet than inactive obese participants at all load stages. In addition, active obese participants showed a significantly higher lipid oxidation rate compared with inactive obese and active overweight and normal-weight participants. VO2net, Enet, and MEnet were similar across active children, regardless of body weight status. CONCLUSIONS: Thirty minutes or more of MVPA per day is associated with a potentiation of aerobic fitness indicators in obese prepubertal children. Moreover, the indices of aerobic fitness of inactive obese children are significantly different from those of active obese and nonobese ones. PMID- 25133418 TI - IL-1beta inhibition in autoimmune inner ear disease: can you hear me now? AB - Clinical vignette: A 51-year-old man with right-sided sudden hearing loss presents to the otology clinic. He has a 4-year history of episodic vertigo of several hours' duration and fluctuating, progressive sensorineural hearing loss in his left ear. The vertigo attacks have not occurred for the last 18 months, and the left ear hearing is consistently poor. The patient's right ear hearing has dropped in the last 36 hours. MRI imaging of brain and temporal bone are normal. A 2-week "burst and taper" of oral prednisone is administered with no effect. Over the next 3 months, serial audiograms show rapidly progressive loss of threshold and word recognition scores on the right side. A trial of high-dose prednisone (60 mg/d for 30 days) results in full recovery of the right ear hearing and substantial improvement in the left ear. As the prednisone dose is slowly tapered over several months, the hearing drops again. PMID- 25133419 TI - Too much of a good thing: immunodeficiency due to hyperactive PI3K signaling. AB - Primary immune deficiency diseases arise due to heritable defects that often involve signaling molecules required for immune cell function. Typically, these genetic defects cause loss of gene function, resulting in primary immune deficiencies such as severe combined immune deficiency (SCID) and X-linked agammaglobulinemia (XLA); however, gain-of-function mutations may also promote immune deficiency. In this issue of the JCI, Deau et al. establish that gain-of function mutations in PIK3R1, which encodes the p85alpha regulatory subunit of class IA PI3Ks, lead to immunodeficiency. These observations are consistent with previous reports that hyperactivating mutations in PIK3CD, which encodes the p110delta catalytic subunit, are capable of promoting immune deficiency. Mutations that reduce PI3K activity also result in defective lymphocyte development and function; therefore, these findings support the notion that too little or too much PI3K activity leads to immunodeficiency. PMID- 25133417 TI - Providers' perspectives regarding the development of a web-based depression intervention for Latina/o youth. AB - Latina/o youth appear to be at significant risk for depression and, of concern, is the high underutilization of mental health services observed in this population. There is a tremendous need for novel intervention methods to better serve the unique needs of this population. This article describes the development of Rise Above (Siempre Sale el Sol), a Web-based, self-help, depression intervention for Latina/o adolescents funded by the National Institute of Mental Health. We applied a cultural adaptation model to an evidence-based depression treatment to reduce potential service barriers and increase the relevance and potential efficacy of the intervention for Latina/o youth. We conducted thematic interviews with 32 national experts to obtain feedback that would inform our application of the cultural adaptation model, the potential efficacy of the intervention, and the feasibility of implementation. Future directions for the evaluation of Rise Above (Siempre Sale el Sol) are described. PMID- 25133420 TI - Play down protein to play up metabolism? AB - Who among us hasn't fantasized about a diet that allows ingestion of a surfeit of calories that are burned off effortlessly by ramping up energy expenditure? In this issue of the JCI, research led by Christopher Morrison suggests that this dream may become a reality; however, a complete understanding of the molecular interface that connects nutrient choices with our cellular metabolism will be required. Laeger et al. show that the expression and secretion of the weight reducing hormone fibroblast growth factor 21 (FGF21) is regulated by dietary proteins and not, as has been heretofore assumed, simply triggered by reduced caloric intake. This study not only sheds new light on the role of FGF21 in systems metabolism, but also on the ways our bodies cope with the ever-changing availability of different dietary macronutrients. PMID- 25133421 TI - Healing the injured vessel wall using microRNA-facilitated gene delivery. AB - Drug-eluting stents have emerged as potent weapons in the treatment of patients with symptomatic coronary artery disease by reducing restenosis rates; however, a significant clinical consequence of these stents is delayed reendothelialization, which may increase the risk of late stent thrombosis. In this issue of the JCI, Santulli and colleagues generated an adenovirus that expresses the cyclin dependent kinase inhibitor p27(Kip1) (p27) and bears four tandem copies of target sequences for the endothelial cell-enriched microRNA (miRNA) miR-126-3p (Ad-p27 126TS) in an attempt to specifically reduce proliferation of vascular smooth muscle cells, but not endothelial cells. Indeed, delivery of Ad-p27-126TS to balloon-injured arteries in rats not only induced faster and more complete reendothelialization, but also effectively improved neointimal hyperplasia, hypercoagulability, and vasoreactivity. Collectively, these findings provide a cogent foundation for the potential therapeutic use of miRNA-facilitated gene delivery strategies to heal vessel wall injury. PMID- 25133422 TI - "RAS"ling beta cells to proliferate for diabetes: why do we need MEN? AB - Adult human pancreatic beta cells are refractory to current therapeutic approaches to enhance proliferation. This reluctance to expand is problematic, especially for people with diabetes who lack sufficient numbers of functional insulin-producing beta cells and could therefore benefit from therapies for beta cell expansion. In this issue of the JCI, Chamberlain et al. describe a surprising series of observations that involve two downstream arms of the RAS signaling pathway, MAPK and RASSF proteins, which also involve the tumor suppressor menin. The findings of this study may help explain the difficulty of inducing beta cell proliferation and may provide leads for therapeutic expansion of human beta cells. PMID- 25133423 TI - Inflammatory lymphangiogenesis in postpartum breast tissue remodeling. AB - Like many cancers, mammary carcinomas use lymphatic vessels to disseminate, and numerous clinical and experimental studies have documented a strong correlation between peritumoral lymphangiogenesis and tumor dissemination. At the same time, many other factors can affect the incidence, invasiveness, and mortality of breast cancer, including lactation history. Although lactation reduces overall cancer risk, patients diagnosed within 5 years of pregnancy have an increased incidence of metastatic disease. In this issue of the JCI, Lyons and colleagues demonstrate that postpartum breast tissue remodeling during involution coincides with inflammatory lymphangiogenesis. In mouse models, cyclooxygenase-2 (COX-2) inhibition during involution reduced the risk of cancer metastasis and correlated with decreased lymphangiogenesis. In addition to lymphangiogenesis, COX-2 inhibition reduces many of the immune-suppressive features of the tumor microenvironment, including development of myeloid-derived suppressor cells and regulatory T cells; therefore, these results support the notion that inhibiting COX-2 during lactation weaning may lessen the incidence of breast cancer metastasis. PMID- 25133424 TI - Menin determines K-RAS proliferative outputs in endocrine cells. AB - Endocrine cell proliferation fluctuates dramatically in response to signals that communicate hormone demand. The genetic alterations that override these controls in endocrine tumors often are not associated with oncogenes common to other tumor types, suggesting that unique pathways govern endocrine proliferation. Within the pancreas, for example, activating mutations of the prototypical oncogene KRAS drive proliferation in all pancreatic ductal adenocarcimomas but are never found in pancreatic endocrine tumors. Therefore, we asked how cellular context impacts K-RAS signaling. We found that K-RAS paradoxically suppressed, rather than promoted, growth in pancreatic endocrine cells. Inhibition of proliferation by K RAS depended on antiproliferative RAS effector RASSF1A and blockade of the RAS activated proproliferative RAF/MAPK pathway by tumor suppressor menin. Consistent with this model, a glucagon-like peptide 1 (GLP1) agonist, which stimulates ERK1/2 phosphorylation, did not affect endocrine cell proliferation by itself, but synergistically enhanced proliferation when combined with a menin inhibitor. In contrast, inhibition of MAPK signaling created a synthetic lethal interaction in the setting of menin loss. These insights suggest potential strategies both for regenerating pancreatic beta cells for people with diabetes and for targeting menin-sensitive endocrine tumors. PMID- 25133425 TI - Periderm prevents pathological epithelial adhesions during embryogenesis. AB - Appropriate development of stratified, squamous, keratinizing epithelia, such as the epidermis and oral epithelia, generates an outer protective permeability barrier that prevents water loss, entry of toxins, and microbial invasion. During embryogenesis, the immature ectoderm initially consists of a single layer of undifferentiated, cuboidal epithelial cells that stratifies to produce an outer layer of flattened periderm cells of unknown function. Here, we determined that periderm cells form in a distinct pattern early in embryogenesis, exhibit highly polarized expression of adhesion complexes, and are shed from the outer surface of the embryo late in development. Mice carrying loss-of-function mutations in the genes encoding IFN regulatory factor 6 (IRF6), IkappaB kinase-alpha (IKKalpha), and stratifin (SFN) exhibit abnormal epidermal development, and we determined that mutant animals exhibit dysfunctional periderm formation, resulting in abnormal intracellular adhesions. Furthermore, tissue from a fetus with cocoon syndrome, a lethal disorder that results from a nonsense mutation in IKKA, revealed an absence of periderm. Together, these data indicate that periderm plays a transient but fundamental role during embryogenesis by acting as a protective barrier that prevents pathological adhesion between immature, adhesion-competent epithelia. Furthermore, this study suggests that failure of periderm formation underlies a series of devastating birth defects, including popliteal pterygium syndrome, cocoon syndrome, and Bartsocas-Papas syndrome. PMID- 25133426 TI - Cyclooxygenase-2-dependent lymphangiogenesis promotes nodal metastasis of postpartum breast cancer. AB - Breast involution following pregnancy has been implicated in the high rates of metastasis observed in postpartum breast cancers; however, it is not clear how this remodeling process promotes metastasis. Here, we demonstrate that human postpartum breast cancers have increased peritumor lymphatic vessel density that correlates with increased frequency of lymph node metastases. Moreover, lymphatic vessel density was increased in normal postpartum breast tissue compared with tissue from nulliparous women. In rodents, mammary lymphangiogenesis was upregulated during weaning-induced mammary gland involution. Furthermore, breast cancer cells exposed to the involuting mammary microenvironment acquired prolymphangiogenic properties that contributed to peritumor lymphatic expansion, tumor size, invasion, and distant metastases. Finally, in rodent models of postpartum breast cancer, cyclooxygenase-2 (COX-2) inhibition during the involution window decreased normal mammary gland lymphangiogenesis, mammary tumor associated lymphangiogenesis, tumor cell invasion into lymphatics, and metastasis. Our data indicate that physiologic COX-2-dependent lymphangiogenesis occurs in the postpartum mammary gland and suggest that tumors within this mammary microenvironment acquire enhanced prolymphangiogenic activity. Further, our results suggest that the prolymphangiogenic microenvironment of the postpartum mammary gland has potential as a target to inhibit metastasis and suggest that further study of the therapeutic efficacy of COX-2 inhibitors in postpartum breast cancer is warranted. PMID- 25133428 TI - A human immunodeficiency caused by mutations in the PIK3R1 gene. AB - Recently, patient mutations that activate PI3K signaling have been linked to a primary antibody deficiency. Here, we used whole-exome sequencing and characterized the molecular defects in 4 patients from 3 unrelated families diagnosed with hypogammaglobulinemia and recurrent infections. We identified 2 different heterozygous splice site mutations that affect the same splice site in PIK3R1, which encodes the p85alpha subunit of PI3K. The resulting deletion of exon 10 produced a shortened p85alpha protein that lacks part of the PI3K p110 binding domain. The hypothetical loss of p85alpha-mediated inhibition of p110 activity was supported by elevated phosphorylation of the known downstream signaling kinase AKT in patient T cell blasts. Analysis of patient blood revealed that naive T and memory B cell counts were low, and T cell blasts displayed enhanced activation-induced cell death, which was corrected by addition of the PI3Kdelta inhibitor IC87114. Furthermore, B lymphocytes proliferated weakly in response to activation via the B cell receptor and TLR9, indicating a B cell defect. The phenotype exhibited by patients carrying the PIK3R1 splice site mutation is similar to that of patients carrying gain-of-function mutations in PIK3CD. Our results suggest that PI3K activity is tightly regulated in T and B lymphocytes and that various defects in the PI3K-triggered pathway can cause primary immunodeficiencies. PMID- 25133427 TI - FGF21 is an endocrine signal of protein restriction. AB - Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet. LP-induced increases in FGF21 were associated with increased phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) in the liver, and both baseline and LP-induced serum FGF21 levels were reduced in mice lacking the eIF2alpha kinase general control nonderepressible 2 (GCN2). Finally, while protein restriction altered food intake, energy expenditure, and body weight gain in WT mice, FGF21-deficient animals did not exhibit these changes in response to a LP diet. These and other data demonstrate that reduced protein intake underlies the increase in circulating FGF21 in response to starvation and a ketogenic diet and that FGF21 is required for behavioral and metabolic responses to protein restriction. FGF21 therefore represents an endocrine signal of protein restriction, which acts to coordinate metabolism and growth during periods of reduced protein intake. PMID- 25133429 TI - PAX7 expression defines germline stem cells in the adult testis. AB - Spermatogenesis is a complex, multistep process that maintains male fertility and is sustained by rare germline stem cells. Spermatogenic progression begins with spermatogonia, populations of which express distinct markers. The identity of the spermatogonial stem cell population in the undisturbed testis is controversial due to a lack of reliable and specific markers. Here we identified the transcription factor PAX7 as a specific marker of a rare subpopulation of A(single) spermatogonia in mice. PAX7+ cells were present in the testis at birth. Compared with the adult testis, PAX7+ cells constituted a much higher percentage of neonatal germ cells. Lineage tracing in healthy adult mice revealed that PAX7+ spermatogonia self-maintained and produced expanding clones that gave rise to mature spermatozoa. Interestingly, in mice subjected to chemotherapy and radiotherapy, both of which damage the vast majority of germ cells and can result in sterility, PAX7+ spermatogonia selectively survived, and their subsequent expansion contributed to the recovery of spermatogenesis. Finally, PAX7+ spermatogonia were present in the testes of a diverse set of mammals. Our data indicate that the PAX7+ subset of A(single) spermatogonia functions as robust testis stem cells that maintain fertility in normal spermatogenesis in healthy mice and mediate recovery after severe germline injury, such as occurs after cancer therapy. PMID- 25133432 TI - Histologic features mimicking mycosis fungoides induced by imiquimod, 5%: a potential pitfall for dermatopathologists. PMID- 25133430 TI - A selective microRNA-based strategy inhibits restenosis while preserving endothelial function. AB - Drugs currently approved to coat stents used in percutaneous coronary interventions do not discriminate between proliferating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). This lack of discrimination delays reendothelialization and vascular healing, increasing the risk of late thrombosis following angioplasty. We developed a microRNA-based (miRNA-based) approach to inhibit proliferative VSMCs, thus preventing restenosis, while selectively promoting reendothelialization and preserving EC function. We used an adenoviral (Ad) vector that encodes cyclin-dependent kinase inhibitor p27(Kip1) (p27) with target sequences for EC-specific miR-126-3p at the 3' end (Ad-p27-126TS). Exogenous p27 overexpression was evaluated in vitro and in a rat arterial balloon injury model following transduction with Ad-p27-126TS, Ad-p27 (without miR-126 target sequences), or Ad-GFP (control). In vitro, Ad-p27-126TS protected the ability of ECs to proliferate, migrate, and form networks. At 2 and 4 weeks after injury, Ad-p27-126TS-treated animals exhibited reduced restenosis, complete reendothelialization, reduced hypercoagulability, and restoration of the vasodilatory response to acetylcholine to levels comparable to those in uninjured vessels. By incorporating miR-126-3p target sequences to leverage endogenous EC specific miR-126, we overexpressed exogenous p27 in VSMCs, while selectively inhibiting p27 overexpression in ECs. Our proof-of-principle study demonstrates the potential of using a miRNA-based strategy as a therapeutic approach to specifically inhibit vascular restenosis while preserving EC function. PMID- 25133431 TI - Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease. AB - BACKGROUND: Autoimmune inner ear disease (AIED) is a rare disease that results in progressive sensorineural hearing loss. Patients with AIED initially respond to corticosteroids; however, many patients become unresponsive to this treatment over time, and there is no effective alternative therapy for these individuals. METHODS: We performed a phase I/II open-label, single-arm clinical trial of the IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients. Given that the etiology of corticosteroid resistance is likely heterogeneous, we used a Simon 2-stage design to distinguish between an unacceptable (<=10%) and an acceptable (>=30%) response rate to anakinra therapy. Subjects received 100 mg anakinra by subcutaneous injection for 84 days, followed by a 180-day observational period. RESULTS: Based on patient responses, the Simon 2-stage rule permitted premature termination of the trial after 10 subjects completed the 84 day drug period, as the target efficacy for the entire trial had been achieved. Of these 10 patients, 7 demonstrated audiometric improvement, as assessed by pure tone average (PTA) and word recognition score (WRS). In these 7 responders, reduced IL-1beta plasma levels correlated with clinical response. Upon discontinuation of treatment, 3 subjects relapsed, which correlated with increased IL-1beta plasma levels. CONCLUSION: We demonstrated that IL-1beta inhibition in corticosteroid-resistant AIED patients was effective in a small cohort of patients and that IL-1beta plasma levels associated with both clinical hearing response and disease relapse. These results suggest that a larger phase II randomized clinical trial of IL-1beta inhibition is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01267994. FUNDING: NIH, Merrill & Phoebe Goodman Otology Research Center, and Long Island Hearing & Speech Society. PMID- 25133433 TI - Ebola hemorrhagic fever in 2014: the tale of an evolving epidemic. PMID- 25133434 TI - Patterns of injury, outcomes, and predictors of in-hospital and 1-year mortality in nonagenarian and centenarian trauma patients. AB - IMPORTANCE: With the dramatic growth in the very old population and their concomitant heightened exposure to traumatic injury, the trauma burden among this patient population is estimated to be exponentially increasing. OBJECTIVE: To determine the clinical outcomes and predictors of in-hospital and 1-year mortality in nonagenarian and centenarian trauma patients (NCTPs). DESIGN, SETTING, AND PARTICIPANTS: All patients 90 years or older admitted to a level 1 academic trauma center between January 1, 2006, and December 31, 2010, with a primary diagnosis of trauma were included. Standard trauma registry data variables were supplemented by systematic medical record review. Cumulative mortality rates at 1, 3, 6, and 12 months after discharge were investigated using the Social Security Death Index. Univariate and multivariable analyses were performed to identify the predictors of in-hospital and 1-year postdischarge cumulative mortalities. MAIN OUTCOMES AND MEASURES: Length of hospital stay, in hospital mortality, and cumulative mortalities at 1, 3, 6, and 12 months after discharge. RESULTS: Four hundred seventy-four NCTPs were included; 71.7% were female, and a fall was the predominant mechanism of injury (96.4%). The mean patient age was 93 years, the mean Injury Severity Score was 12, and the mean number of comorbidities per patient was 4.4. The in-hospital mortality was 9.5% but cumulatively escalated at 1, 3, 6, and 12 months after discharge to 18.5%, 26.4%, 31.3%, and 40.5%, respectively. Independent predictors of in-hospital mortality were the Injury Severity Score (odds ratio [OR], 1.09; 95% CI, 1.02 1.16; P = .01), mechanical ventilation (OR, 6.23; 95% CI, 1.42-27.27; P = .02), and cervical spine injury (OR, 4.37; 95% CI, 1.41-13.50; P = .01). Independent predictors of cumulative 1-year mortality were head injury (OR, 2.65; 95% CI, 1.24-5.67; P = .03) and length of hospital stay (OR, 1.06; 95% CI, 1.02-1.11; P = .005). Cumulative 1-year mortality in NCTPs with a head injury was 51.1% and increased to 73.2% if the Injury Severity Score was 25 or higher and to 78.7% if mechanical ventilation was required. Most NCTPs required rehabilitation; only 8.9% were discharged to home. CONCLUSIONS AND RELEVANCE: Despite low in-hospital mortality, the cumulative mortality rate among NCTPs at 1 year after discharge is significant, particularly in the presence of head injury, spine injury, mechanical ventilation, high injury severity, or prolonged length of hospital stay. These considerations can help guide clinical decisions and family discussions. PMID- 25133435 TI - Breast cancer risk and use of calcium channel blockers using Swedish population registries. PMID- 25133439 TI - Demystifying Merkel. PMID- 25133440 TI - Divine skin. PMID- 25133441 TI - Solving the mystery of Jimmy's red sweat. PMID- 25133442 TI - Circulating adiponectin levels and risk of type 2 diabetes in the Japanese. AB - BACKGROUND: Adiponectin has anti-inflammatory and insulin-sensitizing properties. Prospective studies have consistently shown a lower risk of type 2 diabetes among those with higher circulating adiponectin levels. OBJECTIVE: We examined prospectively the association between serum adiponectin levels and type 2 diabetes risk among Japanese workers, taking visceral fat mass into account. SUBJECTS AND METHODS: Subjects were 4591 Japanese employees who attended a comprehensive health screening in 2008; had biochemical data including serum adiponectin; were free of diabetes at baseline; and received health screening in 2011. Multiple logistic regression analysis was used to examine the association between adiponectin and incidence of diabetes among overall subjects, as well as subgroups. Stratified analyses were carried out according to variables including visceral fat area (VFA). RESULTS: During 3 years of follow-up, 217 diabetic cases were newly identified. Of these, 87% had a prediabetes at baseline. Serum adiponectin level was significantly, inversely associated with incidence of diabetes, with odds ratios (95% confidence interval) adjusted for age, sex, family history, smoking, alcohol drinking, physical activity and body mass index (BMI) for the lowest through highest quartile of adiponectin of 1 (reference), 0.79 (0.55-1.12), 0.60 (0.41-0.88) and 0.40 (0.25-0.64), respectively (P-value for trend <0.01). This association was materially unchanged with adjustment for VFA instead of BMI. After further adjustment for both homeostasis model assessment of insulin resistance and hemoglobin A1c, however, the association became statistically nonsignificant (P-value for trend=0.18). Risk reduction associated with higher adiponectin levels was observed in both participants with and without obesity or insulin resistance at baseline. CONCLUSIONS: RESULTS suggest that higher levels of circulating adiponectin are associated with a lower risk of type 2 diabetes, independently of overall and intra-abdominal fat deposition, and that adiponectin may confer a benefit in both persons with and without insulin resistance. PMID- 25133449 TI - Low serum 25 hydroxyvitamin D is associated with poor clinicopathologic characteristics in female patients with papillary thyroid cancer. AB - BACKGROUND: Vitamin D has recently attracted attention because reduced levels are associated with the prevalence and aggressiveness of several cancers. This study aimed to evaluate the relationship between preoperative serum 25 hydroxyvitamin D (25(OH) vitamin D) levels and clinicopathologic characteristics in female patients with papillary thyroid cancer (PTC). METHODS: A total of 548 female patients who underwent total thyroidectomy for PTC between June 2012 and May 2013 were included. Blood samples were obtained within two weeks prior to surgery. Patients were categorized into four quartiles by preoperative serum 25(OH) vitamin D levels. The clinicopathologic features of PTC were analyzed retrospectively. RESULTS: Preoperative 25(OH) vitamin D was significantly lower in patients with a tumor size of >1 cm (p = 0.041) or lymph node metastasis (LNM; p = 0.043). No significant trends in several clinicopathologic features were observed in relation to increasing serum vitamin D concentrations except decreasing tumor size (p = 0.010). Patients in the second quartile had a greater occurrence of T stage 3/4 (odds ratio (OR) 2.03 [confidence interval (CI) 1.19 3.44]; p = 0.009), LNM (OR 2.03 [CI 1.19-3.44]; p = 0.009), lateral LNM (OR 5.03 [CI 1.66-15.28]; p = 0.004), and extrathyroidal extension (ETE; OR 1.95 [CI 1.15 3.29]; p = 0.013) than those in the fourth quartile. Multivariate analysis showed that patients in the second quartile had a greater occurrence of T stage 3/4 (OR 1.89 [CI 1.08-3.30]; p = 0.026), LNM (OR 2.04 [CI 1.20-3.47]; p = 0.009), lateral LNM (OR 5.12 [CI 1.68-15.59]; p = 0.004), and ETE (OR 1.81 [CI 1.04-3.15]; p = 0.036) than those in the fourth quartile. When the subjects were recategorized into two groups by median 25(OH) vitamin D levels, those with values below the median had a significantly higher risk of T stage 3/4, LNM, lateral LNM, stage III/IV, and ETE. All values except ETE sustained significance after adjustment. CONCLUSION: Lower preoperative serum 25(OH) vitamin D levels appear to be associated with poor clinicopathologic features in female patients with PTC. PMID- 25133451 TI - Decalepisarayalpathra (J. Joseph & V. Chandras.) Venter, an endemic and endangered ethno medicinal plant from Western Ghats, India. AB - Decalepis arayalpatra is an endemic and critically endangered plant of India. May 2014 issue of Natural Products Research publishes the findings of R. S. Verma et al. on the chemical composition of D. arayalpatra. This study was conducted to characterise the root aroma of this plant for possible industrial applications. The authors suggest that due to its peculiar vanilla flavour, the plant could be explored as a potential substitute of vanillin-aroma in the flavour industry. Owing to the fact that D. arayalpatra is a critically endangered plant species, and its habitat is now limited to only the protected areas and reserve forest in southern part of India, and that collecting any plant from such reserve forests for commercial activities is illegal as per the law of the country, this specific conclusion of the authors is totally un-substantiated by the law of land, hence, calls for further review. PMID- 25133450 TI - Sorghum [Sorghum bicolor (L.) Moench] leaf sheath dye protects against cisplatin induced hepatotoxicity and oxidative stress in rats. AB - This study sought to determine the protective effect of dietary inclusion of sorghum leaf sheath dye on cisplatin-induced hepatotoxicity and oxidative stress in rats. Adult male rats were randomly divided into four groups with six animals in each group. Groups I and II were fed a basal diet, while groups III and IV were fed diets containing 0.5% and 1% sorghum leaf sheath dye, respectively, for 20 days before cisplatin administration. Hepatotoxicity was induced by a single dose of cisplatin (7 mg/kg body weight, i.p.), and the experiment was terminated at 3 days after cisplatin injection. The liver and plasma were studied for hepatotoxicity and antioxidant capacity. Cisplatin caused a significant (P<.05) alteration in plasma and liver enzymatic (catalase, glutathione-S-transferase [GST], and superoxide dismutase [SOD]) and nonenzymatic (glutathione [GSH] and vitamin C) antioxidant indices with a concomitant increase in the malondialdehyde (MDA) content; however, there was a significant (P<.05) restoration of the antioxidant status coupled with a significant (P<.05) decrease in the tissue MDA content, after consumption of diets containing sorghum leaf sheath dye. Furthermore, dietary inclusion of sorghum leaf sheath dye caused a marked reduction in the activities of alanine aminotransferase and aspartate aminotransferase after cisplatin administration. However, the ability of the dye to prevent significant cisplatin-induced alteration of both plasma and liver antioxidant indices suggests an antioxidant mechanism of action. Hence, this protective effect of Sorghum bicolor leaf sheath dye against cisplatin-induced hepatotoxicity in rats reflects its potential and beneficial role in the prevention of liver damage associated with cisplatin administration. PMID- 25133452 TI - Actinomycotic mastoiditis complicated by sigmoid sinus thrombosis and labyrinthine fistula. AB - Actinomyces is a rare pathogen that can be the cause of infections in the digestive and urinary tracts, skin, genitalia, and lungs, which generally have an indolent clinical course. However, in some cases these can be locally destructive and become generalized infections. Actinomyces has been previously implicated in infections of the middle ear, nasopharynx, and sinuses, occasionally causing complications such as chronic mastoiditis. Here we describe the case of a 10-year old-male presenting with nausea, vomiting, and headache who developed intracranial complications of actinomycotic mastoiditis. PMID- 25133455 TI - Effectiveness of electronic stability control on single-vehicle accidents. AB - OBJECTIVE: This study aims at evaluating the effectiveness of electronic stability control (ESC) on single-vehicle injury accidents while controlling for a number of confounders influencing the accident risk. METHODS: Using police registered injury accidents from 2004 to 2011 in Denmark with cars manufactured in the period 1998 to 2011 and the principle of induced exposure, 2 measures of the effectiveness of ESC were calculated: The crude odds ratio and the adjusted odds ratio, the latter by means of logistic regression. The logistic regression controlled for a number of confounding factors, of which the following were significant. For the driver: Age, gender, driving experience, valid driving license, and seat belt use. For the vehicle: Year of registration, weight, and ESC. For the accident surroundings: Visibility, light, and location. Finally, for the road: Speed limit, surface, and section characteristics. RESULTS: The present study calculated the crude odds ratio for ESC-equipped cars of getting in a single-vehicle injury accident as 0.40 (95% confidence interval [CI], 0.34-0.47) and the adjusted odds ratio as 0.69 (95% CI, 0.54-0.88). No difference was found in the effectiveness of ESC across the injury severity categories (slight, severe, and fatal). CONCLUSIONS: In line with previous results, this study concludes that ESC reduces the risk for single-vehicle injury accidents by 31% when controlling for various confounding factors related to the driver, the car, and the accident surroundings. Furthermore, it is concluded that it is important to control for human factors (at a minimum age and gender) in analyses where evaluations of this type are performed. PMID- 25133456 TI - Metadata checklist: identification of CHI3L1 and MASP2 as a biomarker pair for liver cancer through integrative secretome and transcriptome analysis. PMID- 25133457 TI - Detection of Salmonella bacterium in drinking water using microring resonator. AB - A new microring resonator system is proposed for the detection of the Salmonella bacterium in drinking water, which is made up of SiO2-TiO2 waveguide embedded inside thin film layer of the flagellin. The change in refractive index due to the binding of the Salmonella bacterium with flagellin layer causes a shift in the output signal wavelength and the variation in through and drop port's intensities, which leads to the detection of Salmonella bacterium in drinking water. The sensitivity of proposed sensor for detecting of Salmonella bacterium in water solution is 149 nm/RIU and the limit of detection is 7 * 10(-4)RIU. PMID- 25133458 TI - Estimated medical cost reductions associated with use of novel oral anticoagulants vs warfarin in a real-world non-valvular atrial fibrillation patient population. AB - OBJECTIVE: RESULTS of randomized clinical trials (RCT) demonstrate that novel oral anticoagulants (NOAC) are effective therapies for reducing the risk of stroke in non-valvular atrial fibrillation (NVAF). Prior medical cost avoidance studies have used warfarin event rates from RCTs, which may differ from patients receiving treatment in a real-world (RW) setting, where the quality of care may not be the same as in a RCT. The purpose of this study was to estimate the change in medical costs related to stroke and major bleeding for each NOAC (apixaban, dabigatran, and rivoraxaban) relative to warfarin in a RW NVAF population. METHODS: Patients (n = 23,525) with a diagnosis of NVAF during 2007-2010 were selected from a Medco population of US health plans. Stroke and major bleeding excluding intracranial hemorrhage (MBEIH) events were identified using diagnosis codes on medical claims. RW reference event rates were calculated during periods of warfarin exposure. RW event rates for NOACs were estimated by multiplying the corresponding relative risk (RR) from the RCTs by each reference rate. Absolute risk reductions (ARR) or number of events avoided per patient year were then estimated. Changes in medical costs associated with each NOAC were calculated by applying the ARR to the 1-year cost for each event. Costs for stroke and MBEIH were obtained from the literature. Drug and international normalized ratio monitoring costs were not considered in this analysis. RESULTS: Compared to RW warfarin, use of apixaban and dabigatran resulted in total (stroke plus MBEIH) medical cost reductions of $1245 and $555, respectively, during a patient year. Rivaroxaban resulted in a medical cost increase of $144. CONCLUSIONS: If relative risk reductions demonstrated in RCTs persist in a RW setting, apixaban would confer the greatest medical cost savings vs warfarin, resulting from significantly lower rates of both stroke and MBEIH. PMID- 25133459 TI - Minnesota multiphasic personality inventory-2-restructured form (MMPI-2-RF) predictors of violating probation after felonious crimes. AB - We compared Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI 2-RF) scores of 25 individuals convicted of felonies who violated probation within 1 year of sentencing with those of 45 similarly sentenced defendants who completed probation successfully. The sample (51 males, 19 females) ranged in age from 18 to 81 years (M = 35.2, SD = 13.8) and had 8 to 16 years of education (M = 11.7, SD = 2.1). The majority were Caucasian (85.7%), but African Americans were also represented (14.3%). Individuals in the sample were primarily convicted of mid-level felonies (F-1: 2.9%; F-2: 14.3%; F-3: 22.9%; F-4: 31.4%; F-5: 12.9%). As hypothesized, moderate to large statistically significant differences between probation completers and violators were found on several MMPI-2-RF scales, including Behavioral/Externalizing Dysfunction, Antisocial Behavior, Juvenile Conduct Problems, Substance Abuse, Aggression, Activation, and Disconstraint. Relative risk ratio analyses indicated that probationers who produced elevated scores on these scales were up to 3 times more likely to violate probation than were those with non-elevated scores. Implications of these results and limitations of our findings are discussed. PMID- 25133460 TI - Measurement of math beliefs and their associations with math behaviors in college students. AB - Our purpose in the present study was to expand understanding of math beliefs in college students by developing 3 new psychometrically tested scales as guided by expectancy-value theory, self-efficacy theory, and health belief model. Additionally, we identified which math beliefs (and which theory) best explained variance in math behaviors and performance by college students and which students were most likely to have problematic math beliefs. Study participants included 368 college math students who completed questionnaires to report math behaviors (attending class, doing homework, reading textbooks, asking for help) and used a 5-point rating scale to indicate a variety of math beliefs. For a subset of 84 students, math professors provided final math grades. Factor analyses produced a 10-item Math Value Scale with 2 subscales (Class Devaluation, No Future Value), a 7-item single-dimension Math Confidence Scale, and an 11-item Math Barriers Scale with 2 subscales (Math Anxiety, Discouraging Words). Hierarchical multiple regression revealed that high levels of the newly discovered class devaluation belief (guided by expectancy-value theory) were most consistently associated with poor math behaviors in college students, with high math anxiety (guided by health belief model) and low math confidence (guided by self-efficacy theory) also found to be significant. Analyses of covariance revealed that younger and male students were at increased risk for class devaluation and older students were at increased risk for poor math confidence. PMID- 25133461 TI - Examining the validity of the Homework Performance Questionnaire: Multi-informant assessment in elementary and middle school. AB - Methods for measuring homework performance have been limited primarily to parent reports of homework deficits. The Homework Performance Questionnaire (HPQ) was developed to assess the homework functioning of students in Grades 1 to 8 from the perspective of both teachers and parents. The purpose of this study was to examine the factorial validity of teacher and parent versions of this scale, and to evaluate gender and grade-level differences in factor scores. The HPQ was administered in 4 states from varying regions of the United States. The validation sample consisted of students (n = 511) for whom both parent and teacher ratings were obtained (52% female, mean of 9.5 years of age, 79% non Hispanic, and 78% White). The cross-validation sample included 1,450 parent ratings and 166 teacher ratings with similar demographic characteristics. The results of confirmatory factor analyses demonstrated that the best-fitting model for teachers was a bifactor solution including a general factor and 2 orthogonal factors, referring to student self-regulation and competence. The best-fitting model for parents was also a bifactor solution, including a general factor and 3 orthogonal factors, referring to student self-regulation, student competence, and teacher support of homework. Gender differences were identified for the general and self-regulation factors of both versions. Overall, the findings provide strong support for the HPQ as a multi-informant, multidimensional measure of homework performance that has utility for the assessment of elementary and middle school students. PMID- 25133462 TI - Measuring annual growth using written expression curriculum-based measurement: An examination of seasonal and gender differences. AB - The purpose of this study was to examine annual growth patterns and gender differences in written expression curriculum-based measurement (WE-CBM) when used in the context of universal screening. Students in second through fifth grade (n = 672) from 2 elementary schools that used WE-CBM as a universal screener participated in the study. Student writing samples were scored for production dependent, production-independent, and accurate-production indicators. Results of latent growth models indicate that for most WE-CBM outcome indicators across most grade levels, average growth was curvilinear, with increasing curvilinearity on all indicators as grade level increased. Evidence of gender differences was mixed with girls having higher initial scores on all WE-CBM indicators except for total words written (second and third grades), correct minus incorrect writing sequences (fourth grade only), and percent correct writing sequences (second fourth grades) where differences were not statistically significant. Despite differences in initial level, there were few gender differences in growth and limited overall between-student variability in linear slope. The results of this study extend research on annual patterns of growth and gender differences in WE CBM by analyzing all 3 types of WE-CBM indicators, including upper elementary grades, and assessing skills more frequently (i.e., 4 to 5 times in 1 year) than in prior research on annual growth. The findings have implications for universal screening in WE-CBM and for understanding gender differences in writing performance. PMID- 25133463 TI - The role of odors and ultrasonic vocalizations in female rat (Rattus norvegicus) partner choice. AB - Intrasexual competition for access to a female mate is believed to be unusual in wild male rats, which suggests that female choosiness could be more important. It has been shown that females spend more time with one male than with others when tested in a multiple partner paradigm. The male of first entry is visited most. The role of ultrasonic vocalizations (USVs) and male odors in the female rat's initial choice to approach one male instead of another are studied in these experiments. In Experiment 1, female rats were allowed to choose between 3 different intact males, whereas in Experiment 2, females could choose between a devocalized male and 2 intact males. Both experiments started with a 15-min period with inaccessible males followed by a 15-min period with accessible males in which the female could copulate with the males of her choice. The results showed that female rats spent more time with the male of first entry over the males visited subsequently. No differences were found in USV subtype patterns emitted by the different males or the time spent sniffing the different males in the period preceding the choice. In addition, the results of Experiment 2 showed that females visited the silent males as much as the vocalizing males. Thus, the present experiments did not offer any evidence suggesting that USVs or individual differences in male odors play any role in female mate choice. Other factors that were not investigated in this study might be involved in female rat mate selection, but it should also be considered that mate selection could be random. PMID- 25133464 TI - Do primates see the solitaire illusion differently? A comparative assessment of humans (Homo sapiens), chimpanzees (Pan troglodytes), rhesus monkeys (Macaca mulatta), and capuchin monkeys (Cebus apella). AB - An important question in comparative psychology is whether human and nonhuman animals share similar principles of perceptual organization. Despite much empirical research, no firm conclusion has been drawn. The Solitaire illusion is a numerosity illusion in humans that occurs when one misperceives the relative number of 2 types of items presented in intermingled sets. To date, no study has investigated whether nonhuman animals perceive the Solitaire illusion as humans do. Here, we compared the perception of the Solitaire illusion in human and nonhuman primates in 3 experiments. We first observed (Experiment 1) the spontaneous behavior of chimpanzees when presented with 2 arrays composed of a different number of preferred and nonpreferred food items. In probe trials, preferred items were presented in the Solitaire pattern in 2 different spatial arrangements (either clustered centrally or distributed on the perimeter). Chimpanzees did not show any misperception of quantity in the Solitaire pattern. Next, humans, chimpanzees, rhesus monkeys, and capuchin monkeys underwent the same testing of relative quantity judgments in a computerized task that also presented the Solitaire illusion (Experiments 2 and 3). Unlike humans, chimpanzees did not appear to perceive the illusion, in agreement with Experiment 1. The performance of rhesus monkeys and capuchin monkeys was also different from that of humans, but was slightly more indicative of a potential Solitaire illusion. On the whole, our results suggest a potential discontinuity in the visual mechanisms underlying the Solitaire illusion between human and nonhuman primates. PMID- 25133465 TI - Chimpanzees (Pan troglodytes) instrumentally help but do not communicate in a mutualistic cooperative task. AB - Chimpanzees cooperate in a variety of contexts, but communicating to influence and regulate cooperative activities is rare. It is unclear whether this reflects chimpanzees' general inability or whether they have found other means to coordinate cooperative activities. In the present study chimpanzees could help a partner play her role in a mutually beneficial food-retrieval task either by transferring a needed tool (transfer condition) or by visually or acoustically communicating the hiding-location of the needed tool (communication condition). Overall, chimpanzees readily helped their partner by delivering the needed tool, but none of them communicated the hiding location of the tool to their partner reliably across trials. These results demonstrate that although chimpanzees can coordinate their cooperative activities by instrumentally helping their partner in her role, they do not readily use communication with their partner for this same end. PMID- 25133466 TI - Discrimination of holograms and real objects by pigeons (Columba livia) and humans (Homo sapiens). AB - The type of stimulus material employed in visual tasks is crucial to all comparative cognition research that involves object recognition. There is considerable controversy about the use of 2-dimensional stimuli and the impact that the lack of the 3rd dimension (i.e., depth) may have on animals' performance in tests for their visual and cognitive abilities. We report evidence of discrimination learning using a completely novel type of stimuli, namely, holograms. Like real objects, holograms provide full 3-dimensional shape information but they also offer many possibilities for systematically modifying the appearance of a stimulus. Hence, they provide a promising means for investigating visual perception and cognition of different species in a comparative way. We trained pigeons and humans to discriminate either between 2 real objects or between holograms of the same 2 objects, and we subsequently tested both species for the transfer of discrimination to the other presentation mode. The lack of any decrements in accuracy suggests that real objects and holograms were perceived as equivalent in both species and shows the general appropriateness of holograms as stimuli in visual tasks. A follow-up experiment involving the presentation of novel views of the training objects and holograms revealed some interspecies differences in rotational invariance, thereby confirming and extending the results of previous studies. Taken together, these results suggest that holograms may not only provide a promising tool for investigating yet unexplored issues, but their use may also lead to novel insights into some crucial aspects of comparative visual perception and categorization. PMID- 25133467 TI - Partner attractiveness moderates the relationship between number of sexual rivals and in-pair copulation frequency in humans (Homo sapiens). AB - Nonhuman males attend to the number of potential sexual rivals in the local environment to assess sperm competition risk. Males of these species sometimes perform more frequent in-pair copulations to increase the likelihood of success in sperm competition. Here, we extend this research to humans, Homo sapiens. We secured self-report data from 393 men in a committed, sexual, heterosexual relationship. The results indicate that men whose in-pair partner has more male coworkers and friends (i.e., potential sexual rivals) also perform more frequent in-pair copulations, but only among men who perceive their partner to be particularly attractive relative to assessments of partners by other men in the sample. This research is the first to empirically investigate the number of potential male rivals in the local environment as a cue to sperm competition risk in humans. Discussion addresses limitations of the current research and highlights directions for future research. PMID- 25133468 TI - Novel perspectives on arrhythmia-induced cardiomyopathy: pathophysiology, clinical manifestations and an update on invasive management strategies. AB - Arrhythmia-induced cardiomyopathy is a partially or completely reversible form of myocardial dysfunction due to sustained supraventricular and ventricular arrhythmias. Asynchrony, rapid cardiac rates and rhythm irregularities are the main factors involved in the development of the disease. The reversible nature of arrhythmia-induced cardiac dysfunction allows only for a retrospective diagnosis of the disease once cardiac function is restored following heart rate control. A high level of suspicion is needed to make a diagnosis at an early stage and prevent further progression of the disease. Although reversible, arrhythmia induced cellular and molecular changes may remain, increasing the risk for sudden death even when normal ejection fraction is restored as well as causing rapid deterioration of cardiac function and development of heart failure symptoms if arrhythmia recurs. Appropriate management based on a combination of pharmacologic and nonpharmacologic strategies to achieve rate control and prevent arrhythmia recurrence is pivotal to avoid further cardiac function deterioration and to control symptoms, significantly reducing the risk of heart failure and sudden cardiac death. PMID- 25133469 TI - Neoadjuvant chemotherapy and short-term morbidity in patients undergoing mastectomy with and without breast reconstruction. AB - IMPORTANCE: Neoadjuvant chemotherapy (NC) is increasingly being used in patients with breast cancer, and evidence-based reports related to its independent effects on morbidity after mastectomy with immediate breast reconstruction are limited. OBJECTIVE: To determine the effect of NC on 30-day postoperative morbidity in women undergoing mastectomy with or without immediate breast reconstruction. DESIGN, SETTING, AND PARTICIPANTS: All women undergoing mastectomy with or without immediate breast reconstruction from January 1, 2005, through December 31, 2011, at university and private hospitals internationally were analyzed using the American College of Surgeons National Surgical Quality Improvement Program 2005-2011 databases. Patients who received NC were compared with those without a history of NC to estimate the relative odds of 30-day postoperative overall, systemic, and surgical site morbidity using model-wise multivariable logistic regression. EXPOSURE: Neoadjuvant chemotherapy. MAIN OUTCOMES AND MEASURES: Thirty-day postoperative morbidity (overall, systemic, and surgical site). RESULTS: Of 85,851 women, 66,593 (77.6%) underwent mastectomy without breast reconstruction, with 2876 (4.3%) receiving NC; 7893 patients were excluded because of missing exposure data. The immediate breast reconstruction population included 19,258 patients (22.4%), with 820 (4.3%) receiving NC. After univariable analysis, NC was associated with a 20% lower odds of overall morbidity in the group undergoing mastectomy without breast reconstruction (odds ratio [OR], 0.80; 95% CI, 0.71-0.91) but had no significant effect in the immediate breast reconstruction group (OR, 0.98; 95% CI, 0.79-1.23). After adjustment for confounding, NC was independently associated with lower overall morbidity in the group undergoing mastectomy without breast reconstruction (OR, 0.61; 95% CI, 0.51 0.73) and the immediate tissue expander reconstruction subgroup (OR, 0.49; 95% CI, 0.30-0.84). Neoadjuvant chemotherapy was associated with decreased odds of systemic morbidity in 4 different populations: complete sample (OR, 0.59; 95% CI, 0.49-0.71), mastectomy without breast reconstruction (OR, 0.59; 95% CI, 0.48 0.72), any immediate breast reconstruction (OR, 0.57; 95% CI, 0.37-0.88), and the tissue expander subgroup (OR, 0.41; 95% CI, 0.23-0.72). CONCLUSIONS AND RELEVANCE: Our study supports the safety of NC in women undergoing mastectomy with or without immediate breast reconstruction. Neoadjuvant chemotherapy is associated with lower overall morbidity in the patients undergoing mastectomy without breast reconstruction and in those undergoing tissue expander breast reconstruction. In addition, the odds of systemic morbidity were decreased in patients undergoing mastectomy with and without immediate breast reconstruction. The mechanisms behind the protective association of NC remain unknown and warrant further investigation. PMID- 25133470 TI - The Association Between Exergaming and Physical Activity in Young Adults. AB - BACKGROUND: Compared with traditional nonactive video games, exergaming contributes significantly to overall daily physical activity (PA) in experimental studies, but the association in observational studies is not clear. METHODS: Data were available in the 2011 to 2012 wave of the Nicotine Dependence in Teens (NDIT) study (N = 829). Multivariable sex-stratified models assessed the association between exergaming (1-3 times per month in the past year) and minutes of moderate and vigorous physical activity in the previous week, and the association between exergaming and meeting PA recommendations. RESULTS: Compared with male exergamers, female exergamers were more likely to believe exergames were a good way to integrate PA into their lives (89% vs 62%, P = .0001). After we adjusted for covariates, male exergamers were not significantly different from male nonexergamers in minutes of PA. Female exergamers reported 47 more minutes of moderate PA in the previous week compared with female nonexergamers (P = .03). There was no association between exergaming and meeting PA recommendations. CONCLUSIONS: Exergaming contributes to moderate minutes of PA among women but not among men. Differences in attitudes toward exergaming should be further explored. PMID- 25133472 TI - Long-term follow-up of hearing preservation in electric-acoustic stimulation patients. AB - BACKGROUND: Hearing preservation (HP) surgery was initiated more than 10 years ago for combined electric and acoustic stimulation (EAS). Preserved residual low frequency hearing has been demonstrated to improve speech perception in noise as well as music appreciation in EAS users up to 2 years. Multiple study groups aimed to evaluate initial loss of residual hearing (RH) as a consequence of HP surgery. However, after 1 year and 2 years of follow-up, further decline was reported. This study aimed to determine RH, speech perception, and the subjective benefits of EAS 10 years after HP surgery. SUBJECTS AND METHODS: Nine postlingual EAS partially deaf patients who underwent HP surgery at Antwerp University Hospital were included in this study (11 implanted ears). Hearing preservation (0% = loss of hearing; >0%-25% = minimal HP; >25%-75% = partial HP; >75% = complete HP), speech perception and subjective benefits were evaluated preoperatively; at 3, 6, 12, 18, and 24 months postoperatively; and annually thereafter. RESULTS: Complete HP was obtained in three of 11 ears; partial HP in five of 11 ears; and minimal HP in two of 11 ears, measured during their most recent follow-up. One subject lost his RH completely across time. The mean rate of HP was 48% (ranging from 6 months up to 10 years postoperatively). Speech perception analysis up to 10 years showed a continuous statistically significant improvement. The maximum subjective benefit was reached 3 months after implantation and subsequently remained statistically significant unchanged for the next 10 years. CONCLUSION: Long-term HP in EAS users after HP surgery is feasible, although a small continuous decline of HP rate of 3% per year was observed (measured from first fitting up to 6 years postoperative). Nevertheless, a continuous improvement was found in the speech perception results of the EAS users across 10 years. Moreover, the positive subjective benefit, assessed 3 months postoperative, remained stable up to 10 years. PMID- 25133471 TI - Karyotype-specific ear and hearing problems in young adults with Turner syndrome and the effect of oxandrolone treatment. AB - OBJECTIVE: To evaluate karyotype-specific ear and hearing problems in young-adult patients with Turner syndrome (TS) and assess the effects of previous treatment with oxandrolone (Ox). STUDY DESIGN: Double-blind follow-up study. SETTING: University hospital. PATIENTS: Sixty-five TS patients (mean age, 24.3 yr) previously treated with growth hormone combined with placebo, Ox 0.03 mg/kg per day, or Ox 0.06 mg/kg per day from the age of 8 years and estrogen from the age of 12 years. INTERVENTION: Ear examination was performed according to standard clinical practice. Air- and bone conduction thresholds were measured in decibel hearing level. MAIN OUTCOME MEASURES: We compared patients with total monosomy of the short arm of the X chromosome (Xp), monosomy 45,X and isochromosome 46,X,i(Xq), with patients with a partial monosomy Xp, mosaicism or other structural X chromosomal anomalies. We assessed the effect of previous Ox treatment. RESULTS: Sixty-six percent of the patients had a history of recurrent otitis media. We found hearing loss in 66% of the ears, including pure sensorineural hearing loss in 32%. Hearing thresholds in patients with a complete monosomy Xp were about 10 dB worse compared with those in patients with a partial monosomy Xp. Air- and bone conduction thresholds were not different between the placebo and Ox treatment groups. CONCLUSION: Young-adult TS individuals frequently have structural ear pathology, and many suffer from hearing loss. This indicates that careful follow-up to detect ear and hearing problems is necessary, especially for those with a monosomy 45,X or isochromosome 46,X,i(Xq). Ox does not seem to have an effect on hearing. PMID- 25133473 TI - Ebola, ethics, and public health: what next? PMID- 25133474 TI - Rapidly enlarging nodular plaque on the leg. PMID- 25133475 TI - Gastrointestinal bleeding. AB - A number of interesting abstracts on gastrointestinal bleeding and endoscopy were presented at Digestive Disease Week (DDW) this year (3 - 6 May 2014, Chicago, Illinois). The following abstracts are those that have particular high clinical importance and the potential for direct impact on the endoscopic care of patients with gastrointestinal bleeding. PMID- 25133476 TI - Colonoscopy. PMID- 25133477 TI - Endoscopic ultrasound. AB - Endoscopic ultrasound (EUS) continues to present a rich source of innovation, allowing it to evolve from a diagnostic procedure to a therapeutic modality. This was obvious from the numerous high-quality presentations at the 2014 Digestive Disease Week (DDW) held in Chicago, Illinois. This review discusses several of the presented abstracts of innovations in the field of EUS. PMID- 25133478 TI - Capsule endoscopy and deep enteroscopy. AB - During the 2014 Digestive Disease Week in Chicago, many high-quality studies on small-bowel endoscopy were presented. The most relevant abstracts from around the world of two complementary procedures - capsule endoscopy and deep enteroscopy - which have seen rapid changes in recent years, have been selected for this review. PMID- 25133479 TI - Endoscopic retrograde cholangiopancreatography. AB - New technological developments in endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and treatment have been slow to progress. However, several informative study results were presented during the 2014 Digestive Disease Week (DDW; 3 - 6 May; Chicago, Illinois, USA) in specific ERCP areas, such as prevention of post-ERCP pancreatitis using nonsteroidal anti-inflammatory drugs and pancreatic duct stenting. Novel and interesting study results regarding preoperative stent selection for periampullary tumors, metal stents for hilar stricture or for prevention of duodenal reflux, and intraductal biliary tumor ablation using photodynamic therapy or radiofrequency ablation were discussed. Study results presented at the meeting regarding single-operator cholangioscopy using the SpyGlass system or direct peroral cholangioscopy have indicated the possibility of future development. Results using peroral pancreatoscopy and confocal laser endomicroscopy for biliary lesions, including strictures, were also presented. PMID- 25133480 TI - Endoscopy innovations. AB - Innovation everywhere for everybody - this is the way we can summarize the 2014 Digestive Disease Week, which was held in Chicago, Illinois, last May. Many sessions introduced new innovative materials and concepts. From the robot of the future to the simplest ideas, the congress was fertile and sometimes full of surprises. Abstracts representing significant progress and innovations in the field of digestive endoscopy are reviewed here. PMID- 25133481 TI - Esophageal diseases. PMID- 25133482 TI - Lyn tyrosine kinase regulates androgen receptor expression and activity in castrate-resistant prostate cancer. AB - Castrate-resistant prostate cancer (CRPC) progression is a complex process by which prostate cells acquire the ability to survive and proliferate in the absence or under very low levels of androgens. Most CRPC tumors continue to express the androgen receptor (AR) as well as androgen-responsive genes owing to reactivation of AR. Protein tyrosine kinases have been implicated in supporting AR activation under castrate conditions. Here we report that Lyn tyrosine kinase expression is upregulated in CRPC human specimens compared with hormone naive or normal tissue. Lyn overexpression enhanced AR transcriptional activity both in vitro and in vivo and accelerated CRPC. Reciprocally, specific targeting of Lyn resulted in a decrease of AR transcriptional activity in vitro and in vivo and prolonged time to castration. Mechanistically, we found that targeting Lyn kinase induces AR dissociation from the molecular chaperone Hsp90, leading to its ubiquitination and proteasomal degradation. This work indicates a novel mechanism of regulation of AR stability and transcriptional activity by Lyn and justifies further investigation of the Lyn tyrosine kinase as a therapeutic target for the treatment of CRPC.Oncogenesis (2014) 3, e115; doi:10.1038/oncsis.2014.30; published online 18 August 2014. PMID- 25133485 TI - The promise of curcumin-phosphatidylcholine complex for cardiometabolic diseases: more than just 'more curcumin'. PMID- 25133483 TI - The inhibitor of kappa B kinase-epsilon regulates MMP-3 expression levels and can promote lung metastasis. AB - The factors that determine the ability of metastatic tumor cells to expand and grow in specific secondary site(s) are not yet fully understood. Matrix metalloproteinases (MMP) were identified as potential regulators of the site specificity of metastasis. We found that lung carcinoma cells ectopically expressing high levels of the receptor for the type I insulin like growth factor receptor (M27(R) cells) had a significant reduction in MMP-3 expression levels and this coincided with reduced metastasis to the lung. We used these cells to further investigate signaling pathways regulating MMP-3 expression and the role that MMP-3 plays in lung metastasis. We show that ectopic IkappaB kinase E (IKKE) expression in these cells partly restored MMP-3 expression levels and also sensitized MMP-3 transcription to induction by phorbol 12-myristate 13-acetate (PMA). This increase in MMP-3 production was due to increased activation of several signal transduction mediators, including protein kinase C alpha, ERK2, Akt and the transcription factor p65. Furthermore, reconstitution of MMP-3 expression in M27(R) cells restored their ability to colonize the lung whereas silencing of MMP-3 in M27 cells reduced metastases. Collectively, our results implicate IKKE as a central regulator of PMA-induced cell signaling and MMP-3 expression and identify MMP-3 as an enabler of tumor cell expansion in the lung.Oncogenesis (2014) 3, e116; doi:10.1038/oncsis.2014.28; published online 18 August 2014. PMID- 25133484 TI - Dual targeting of ErbB-2/ErbB-3 results in enhanced antitumor activity in preclinical models of pancreatic cancer. AB - ErbB-3 and its ligand NRG-1beta are key players in driving oncogenic signaling and resistance to therapy through the activation of the PI3K/Akt pathway. We have recently reported that EV20, a humanized anti-ErbB3 antibody, possesses a marked antitumor activity in a variety of human tumor models, including pancreatic cancer (PC). Here, we report that despite epidermal growth factor receptor overexpression, PC cells are more sensitive to NRG-1beta than EGF in terms of Akt activation and cell proliferation. Using stable ErbB-3-knocked down cells and EV20 in combination with trastuzumab, we showed that dual targeting of ErbB-2 and ErbB-3 was necessary to completely abrogate ErbB-3 signaling and to impair cell proliferation. Similarly, enhanced therapeutic efficacy of the antibody combination was seen in xenografts originating from K-Ras-mutated HPAF-II and SW1990 cells, without increasing the toxicity. These results indicate that dual targeting of ErbB-2 and ErbB-3 could represent a new therapeutic approach in PC.Oncogenesis (2014) 3, e117; doi:10.1038/oncsis.2014.31; published online 18 August 2014. PMID- 25133486 TI - Prevalence of and attitudes about distracted driving in college students. AB - OBJECTIVE: To identify current distracted driving (DD) behaviors among college students, primarily those involving cell phone use, and elucidate the opinions of the students on the most effective deterrent or intervention for reducing cell phone use. METHODS: Students enrolled at 12 colleges and universities were recruited to participate in an online, anonymous survey. Recruitment was done via school-based list-serves and posters. School sizes ranged from 476 to over 30,000. The validated survey included 38 questions; 17 were specifically related to distracted driving. RESULTS: Four thousand nine hundred sixty-four participants completed the surveys; the average age was 21.8, 66% were female, 82.7% were undergraduates, and 47% were white/non-Hispanic. Additionally, 4,517 (91%) reported phoning and/or texting while driving; 4,467 (90%) of drivers said they talk on the phone while driving; 1,241 (25%) reported using a hands-free device "most of the time"; 4,467 (90%) of drivers reported texting while driving; 2,488 (50%) reported sending texts while driving on the freeway; 2,978 (60%) while in stop-and-go traffic or on city streets; and 4,319 (87%) at traffic lights. Those who drove more often were more likely to drive distracted. When asked about their capability to drive distracted, 46% said they were capable or very capable of talking on a cell phone and driving, but they felt that only 8.5% of other drivers were capable. In a multivariate model, 9 predictors explained 44% of the variance in DD, which was statistically significant, F (17, 4945) = 224.31; P <.0001; R(2) = 0.44. The four strongest predictors (excluding driving frequency) were self-efficacy (i.e., confidence) in driving while multitasking (beta = 0.37), perception of safety of multitasking while driving (beta = 0.19), social norms (i.e., observing others multitasking while driving; beta = 0.29), and having a history of crashing due to multitasking while driving (beta = 0.11). CONCLUSIONS: Distracted driving is a highly prevalent behavior among college students who have higher confidence in their own driving skills and ability to multitask than they have in other drivers' abilities. Drivers' self-efficacy for driving and multitasking in the car, coupled with a greater likelihood of having witnessed DD behaviors in others, greatly increased the probability that a student would engage in DD. Most students felt that policies, such as laws impacting driving privilege and insurance rate increases, would influence their behavior. PMID- 25133487 TI - Home visit program improves technique survival in peritoneal dialysis. AB - BACKGROUND: Peritoneal dialysis (PD) is a home therapy, and technique survival is related to the adherence to PD prescription at home. The presence of a home visit program could improve PD outcomes. We evaluated its effects on clinical outcome during 1 year of follow-up. METHODS: This was a case-control study. The case group included all 96 patients who performed PD in our center on January 1, 2013, and who attended a home visit program; the control group included all 92 patients who performed PD on January 1, 2008. The home visit program consisted of several additional visits to reinforce patients' confidence in PD management in their own environment. Outcomes were defined as technique failure, peritonitis episode, and hospitalization. Clinical and dialysis features were evaluated for each patient. RESULTS: The case group was significantly older (p = 0.048), with a lower grade of autonomy (p = 0.033), but a better hemoglobin level (p = 0.02) than the control group. During the observational period, we had 11 episodes of technique failure. We found a significant reduction in the rate of technique failure in the case group (p = 0.004). Furthermore, survival analysis showed a significant extension of PD treatment in the patients supported by the home visit program (52 vs. 48.8 weeks, p = 0.018). We did not find any difference between the two groups in terms of peritonitis and hospitalization rate; however, trends toward a reduction of Gram-positive peritonitis rates as well as prevalence and duration of hospitalization related to PD problems were identified in the case group. The retrospective nature of the analysis was a limitation of this study. CONCLUSION: The home visit program improves the survival of PD patients and could reduce the rate of Gram-positive peritonitis and hospitalization. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=365168. PMID- 25133489 TI - Maternal and fetal signs and symptoms associated with uterine rupture in women with prior cesarean delivery. AB - Abstract Objective: To describe the association between maternal and fetal physical signs and symptoms (signs/symptoms) and childbirth outcomes in women with prior cesarean delivery (CD). Methods: Cases of uterine rupture at a single institution were reviewed to examine risk factors for experiencing signs/symptoms and poor childbirth outcomes. Results: Among 21 014 deliveries, 3252 (15.5%) had prior CD, and 75 (2.3%) had uterine rupture. Of these, 66 (88.0%) labored. Among those who labored, 51 (77.3%) demonstrated signs/symptoms prior to delivery. Signs/symptoms included vaginal bleeding, abdominal pain, fetal bradycardia and decreased fetal heart rate (FHR) variability. Laboring patients with signs/symptoms were seven times more likely than those without them to have poor maternal/neonatal outcome (27/51 [52.9%] versus 2/15 [13.3%], OR = 7.31 [95% CI 1.34-52.43], p = 0.0155). In multivariate analysis, risk factors for poor fetal outcome were cervical ripening (OR 4.99 [95% CI 0.86-28.99, p = 0.0735) and prolonged FHR deceleration/bradycardia (OR 2.78 [95% CI 0.86-9.10], p = 0.0905). Fetal tachycardia was a risk factor for poor maternal outcome (OR 8.10 [95% CI 1.40-46.84], p = 0.0195). Conclusions: Among laboring women with uterine rupture, 77% demonstrated maternal or fetal signs/symptoms before delivery. The presence of at least one sign/symptom identified nearly all laboring patients (27/29 [93.1%]) with poor outcomes. PMID- 25133488 TI - Hospital performance for pharmacologic venous thromboembolism prophylaxis and rate of venous thromboembolism : a cohort study. AB - IMPORTANCE: Hospitalization for acute medical illness is associated with increased risk of venous thromboembolism (VTE). Although efforts designed to increase use of pharmacologic VTE prophylaxis are intended to reduce hospital associated VTE, whether higher rates of prophylaxis reduce VTE in medical patients is unknown. OBJECTIVE: To examine the association between pharmacologic VTE prophylaxis rates and hospital-associated VTE. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, multicenter cohort study conducted at 35 Michigan hospitals participating in a statewide quality collaborative from January 1, 2011, through September 13, 2012. Trained medical record abstractors at each hospital collected data from 31 260 general medical patients. Use of VTE prophylaxis on admission, VTE risk factors, and VTE events 90 days after hospital admission were recorded using a combination of medical record review and telephone follow-up. Hospitals were grouped into tertiles of performance based on rate of pharmacologic prophylaxis use on admission for at-risk patients. MAIN OUTCOMES AND MEASURES: Association between hospital performance and time to development of VTE within 90 days of hospital admission. RESULTS: A total of 14 563 of 20 794 patients (70.0%) eligible for pharmacologic prophylaxis received prophylaxis on admission. The rates of pharmacologic prophylaxis use at hospitals in the high-, moderate-, and low-performance tertiles were 85.8%, 72.6%, and 55.5%, respectively. A total of 226 VTE events occurred during 1 765 449 days of patient follow-up. Compared with patients at hospitals in the highest-performance tertile, the hazard of VTE in patients at hospitals in moderate-performance (hazard ratio, 1.10; 95% CI, 0.74-1.62) and low-performance (hazard ratio, 0.96, 95% CI, 0.63-1.45) tertiles did not differ after adjusting for potential confounders. Results remained robust when examining mechanical prophylaxis, prophylaxis use throughout the hospitalization, and subsequent inpatient stays after discharge from the index hospitalization. CONCLUSIONS AND RELEVANCE: The occurrence of 90-day VTE in medical patients after hospitalization is low. Patients who receive care at hospitals that have lower rates of pharmacologic prophylaxis do not have higher adjusted hazards of VTE, even after accounting for individual receipt of pharmacologic prophylaxis. Efforts to increase rates of pharmacologic VTE prophylaxis in hospitalized medical patients may not substantively reduce this adverse outcome. PMID- 25133490 TI - Neurolysis and upper trunk brachial plexus birth palsy. Response. PMID- 25133492 TI - Effects of a six-month walking intervention on depression in inactive post menopausal women: a randomized controlled trial. AB - OBJECTIVES: Physical inactivity and advanced age are associated with risk of depressive disorders. Physical activity can reduce depressive symptoms in older subjects with depressive disorders. We investigated whether a walking intervention program may decrease the occurrence of depressive symptoms in inactive post-menopausal women without depression. METHOD: A total of 121 participants aged 57-75 years were randomly assigned to a six-month moderate intensity walking intervention (three times a week, 40 minutes per session, supervised and home-based) or to a control group (waiting list). Inactivity was assessed using the Physical Activity Questionnaire for the Elderly. Depression levels were measured pre- and post-intervention with the Beck depression inventory (BDI). Several baseline measures were considered as possible predictors of post-intervention BDI score. RESULTS: Participants in the walking intervention showed a significant decrease in depression as compared with controls. Baseline cognitive-BDI subscore, subjective health status, body mass index and adherence were post-intervention BDI score predictors. CONCLUSION: A six-month, three session per week, moderate intensity walking intervention with a minimal 50% adherence rate reduces depression in post-menopausal women at risk for depression due to physical inactivity. This type of walking intervention could be considered as a widely accessible prevention strategy to prevent depressive symptoms in post menopausal women at risk of depression. PMID- 25133491 TI - Effect of topical tranexamic acid on bleeding and quality of surgical field during functional endoscopic sinus surgery in patients with chronic rhinosinusitis: a triple blind randomized clinical trial. AB - BACKGROUND: The effect of tranexamic acid (TXA) on bleeding and improvement of surgical field during functional endoscopic sinus surgery (FESS) is not clear yet. This study was conducted to answer this question. METHODS: This trial was conducted on 60 patients with chronic sinusitis at Beasat Hospital, Hamadan, Iran, from April to November 2013. Thirty patients in the intervention group received three pledgets soaked with TXA 5% and phenylephrine 0.5% for 10 minutes in each nasal cavity before surgery. Thirty patients in the control group received phenylephrine 0.5% with the same way. The amount of bleeding and the quality of surgical field were evaluated at 15, 30, and 45 minutes after the start of surgery using Boezaart grading. RESULTS: The quality of the surgical field in the intervention group compared to the control group was significantly better in the first quarter (P = 0.002) and the second quarter (P = 0.003) but not in the third quarter (P = 0.163). Furthermore, the amount of bleeding was much less during all periods in the intervention group than in the control group (P = 0.001). CONCLUSION: Topical TXA can efficiently reduce bleeding and improve the surgical field in FESS in patients with rhinosinusitis. Based on these findings, topical TXA may be a useful method for providing a suitable surgical field during the first 30 minutes after use. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT201212139014N15. PMID- 25133493 TI - Prognosis evaluation in patients with hepatocellular carcinoma after hepatectomy: comparison of BCLC, TNM and Hangzhou criteria staging systems. AB - PURPOSE: This study is to evaluate the Hangzhou criteria (HC) for patients with HCC undergoing surgical resection and to identify whether this staging system is superior to other staging systems in predicting the survival of resectable HCC. METHOD: 774 HCC patients underwent surgical resection between 2007 and 2009 in West China Hospital were enrolled retrospectively. Predictors of survival were identified using the Kaplan-Meier method and the Cox model. The disease state was staged by the HC, as well as by the TNM and BCLC staging systems. Prognostic powers were quantified using a linear trend chi2 test, c-index, and the likelihood ratio (LHR) chi2 test and correlated using Cox's regression model adjusted using the Akaike information criterion (AIC). RESULTS: Serum AFP level (P = 0.02), tumor size (P<0.001), tumor number (P<0.001), portal vein invasion (P<0.001), hepatic vein invasion (P<0.001), tumor differentiation (P<0.001), and distant organ (P = 0.016) and lymph node metastasis (P<0.001) were identified as independent risk factors of survival after resection by multivariate analysis. The comparison of the different staging system results showed that BCLC had the best homogeneity (likelihood ratio chi2 test 151.119, P<0.001), the TNM system had the best monotonicity of gradients (linear trend chi2 test 137.523, P<0.001), and discriminatory ability was the highest for the BCLC (the AUCs for 1-year mortality were 0.759) and TNM staging systems (the AUCs for 3-, and 5-year mortality were 0.738 and 0.731, respectively). However, based on the c-index and AIC, the HC was the most informative staging system in predicting survival (c index 0.6866, AIC 5924.4729). CONCLUSIONS: The HC can provide important prognostic information after surgery. The HC were shown to be a promising survival predictor in a Chinese cohort of patients with resectable HCC. PMID- 25133494 TI - Fine-tuning of Smad protein function by poly(ADP-ribose) polymerases and poly(ADP ribose) glycohydrolase during transforming growth factor beta signaling. AB - BACKGROUND: Initiation, amplitude, duration and termination of transforming growth factor beta (TGFbeta) signaling via Smad proteins is regulated by post translational modifications, including phosphorylation, ubiquitination and acetylation. We previously reported that ADP-ribosylation of Smads by poly(ADP ribose) polymerase 1 (PARP-1) negatively influences Smad-mediated transcription. PARP-1 is known to functionally interact with PARP-2 in the nucleus and the enzyme poly(ADP-ribose) glycohydrolase (PARG) can remove poly(ADP-ribose) chains from target proteins. Here we aimed at analyzing possible cooperation between PARP-1, PARP-2 and PARG in regulation of TGFbeta signaling. METHODS: A robust cell model of TGFbeta signaling, i.e. human HaCaT keratinocytes, was used. Endogenous Smad3 ADP-ribosylation and protein complexes between Smads and PARPs were studied using proximity ligation assays and co-immunoprecipitation assays, which were complemented by in vitro ADP-ribosylation assays using recombinant proteins. Real-time RT-PCR analysis of mRNA levels and promoter-reporter assays provided quantitative analysis of gene expression in response to TGFbeta stimulation and after genetic perturbations of PARP-1/-2 and PARG based on RNA interference. RESULTS: TGFbeta signaling rapidly induces nuclear ADP-ribosylation of Smad3 that coincides with a relative enhancement of nuclear complexes of Smads with PARP-1 and PARP-2. Inversely, PARG interacts with Smads and can de-ADP ribosylate Smad3 in vitro. PARP-1 and PARP-2 also form complexes with each other, and Smads interact and activate auto-ADP-ribosylation of both PARP-1 and PARP-2. PARP-2, similar to PARP-1, negatively regulates specific TGFbeta target genes (fibronectin, Smad7) and Smad transcriptional responses, and PARG positively regulates these genes. Accordingly, inhibition of TGFbeta-mediated transcription caused by silencing endogenous PARG expression could be relieved after simultaneous depletion of PARP-1. CONCLUSION: Nuclear Smad function is negatively regulated by PARP-1 that is assisted by PARP-2 and positively regulated by PARG during the course of TGFbeta signaling. PMID- 25133495 TI - Is there a benefit in receiving concurrent chemoradiotherapy for elderly patients with inoperable thoracic esophageal squamous cell carcinoma? AB - BACKGROUND AND PURPOSE: The benefit of concurrent chemoradiotherapy (CCRT) in elderly patients with inoperable esophageal squamous cell carcinoma (SCC) is controversial. This study aimed to assess the efficiency and safety of CCRT in elderly thoracic esophageal cancer patients. METHODS AND MATERIALS: Between January 2002 and December 2011, 128 patients aged 65 years or older treated with CCRT or radiotherapy (RT) alone for inoperable thoracic esophageal SCC were analyzed retrospectively (RT alone, n = 55; CCRT, n = 73). RESULTS: No treatment related deaths occurred and no patients experienced any acute grade 4 non hematologic toxicities. Patients treated with CCRT developed more severe acute toxicities than patients who received RT alone. The 3-year overall survival (OS) rate was 36.1% for CCRT compared with 28.5% following RT alone (p = 0.008). Multivariate analysis identified T stage and treatment modality as independent prognostic factors for survival. Further analysis revealed that survival was significantly better in the CCRT group than in the RT alone group for patients <= 72 years. Nevertheless, the CCRT group had a similar OS to the RT group for patients > 72 years. CONCLUSION: Our results suggest that elderly patients with inoperable thoracic esophageal SCC could benefit from CCRT, without major toxicities. However, for patients older than 72 years, CCRT is not superior to RT alone in terms of survival benefit. PMID- 25133496 TI - GPCRsort-responding to the next generation sequencing data challenge: prediction of G protein-coupled receptor classes using only structural region lengths. AB - Next generation sequencing (NGS) and the attendant data deluge are increasingly impacting molecular life sciences research. Chief among the challenges and opportunities is to enhance our ability to classify molecular target data into meaningful and cohesive systematic nomenclature. In this vein, the G protein coupled receptors (GPCRs) are the largest and most divergent receptor family that plays a crucial role in a host of pathophysiological pathways. For the pharmaceutical industry, GPCRs are a major drug target and it is estimated that 60%-70% of all medicines in development today target GPCRs. Hence, they require an efficient and rapid classification to group the members according to their functions. In addition to NGS and the Big Data challenge we currently face, an emerging number of orphan GPCRs further demand for novel, rapid, and accurate classification of the receptors since the current classification tools are inadequate and slow. This study presents the development of a new classification tool for GPCRs using the structural features derived from their primary sequences: GPCRsort. Comparison experiments with the current known GPCR classification techniques showed that GPCRsort is able to rapidly (in the order of minutes) classify uncharacterized GPCRs with 97.3% accuracy, whereas the best available technique's accuracy is 90.7%. GPCRsort is available in the public domain for postgenomics life scientists engaged in GPCR research with NGS: http://bioserver.ceng.metu.edu.tr/GPCRSort . PMID- 25133497 TI - Multi-scales analysis of primate diversity and protected areas at a megadiverse region. AB - In this paper, we address the question of what proportion of biodiversity is represented within protected areas. We assessed the effectiveness of different protected area types at multiple scales in representing primate biodiversity in the Brazilian Legal Amazon. We used point locality data and distribution data for primate species within 1 degrees , 0.5 degrees , and 0.25 degrees spatial resolution grids, and computed the area of reserves within each cell. Four different approaches were used - no reserves (A), exclusively strict use reserves (B), strict and sustainable use reserves (C), and strict and sustainable use reserves and indigenous lands (D). We used the complementarity concept to select reserve networks. The proportions of cells that were classified as reserves at a grid resolution of 1 degrees were 37%, 64%, and 88% for approaches B, C and D, respectively. Our comparison of these approaches clearly showed the effect of an increase in area on species representation. Representation was consistently higher at coarser resolutions, indicating the effect of grain size. The high number of irreplaceable cells for selected networks identified based on approach A could be attributed to the use of point locality occurrence data. Although the limited number of point occurrences for some species may have been due to a Wallacean shortfall, in some cases it may also be the result of an actual restricted geographic distribution. The existing reserve system cannot be ignored, as it has an established structure, legal protection status, and societal recognition, and undoubtedly represents important elements of biodiversity. However, we found that strict use reserves (which are exclusively dedicated to biodiversity conservation) did not effectively represent primate species. This finding may be related to historical criteria for selecting reserves based on political, economic, or social motives. PMID- 25133498 TI - Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup. AB - BACKGROUND: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments (ECTR) in poisoning and the results are presented here for acetaminophen (APAP). METHODS: After a systematic review of the literature, a subgroup selected and reviewed the articles and summarized clinical and toxicokinetic data in order to propose structured voting statements following a pre-determined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Following discussion, a second vote determined the final recommendations. RESULTS: Twenty-four articles (1 randomized controlled trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or case series) were identified, yielding an overall very low quality of evidence for all recommendations. Clinical data on 135 patients and toxicokinetic data on 54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is not warranted in most cases of APAP poisoning. However, given that APAP is dialyzable, the workgroup agreed that ECTR is suggested in patients with excessively large overdoses who display features of mitochondrial dysfunction. This is reflected by early development of altered mental status and severe metabolic acidosis prior to the onset of hepatic failure. Specific recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is not administered (1D), signs of mitochondrial dysfunction and an APAP concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960 mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the preferred ECTR modality in APAP poisoning (1D). CONCLUSION: APAP is amenable to extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare situations when the efficacy of NAC has not been definitively demonstrated. PMID- 25133500 TI - High throughput micro-well generation of hepatocyte micro-aggregates for tissue engineering. AB - The main challenge in hepatic tissue engineering is the fast dedifferentiation of primary hepatocytes in vitro. One successful approach to maintain hepatocyte phenotype on the longer term is the cultivation of cells as aggregates. This paper demonstrates the use of an agarose micro-well chip for the high throughput generation of hepatocyte aggregates, uniform in size. In our study we observed that aggregation of hepatocytes had a beneficial effect on the expression of certain hepatocyte specific markers. Moreover we observed that the beneficial effect was dependent on the aggregate dimensions, indicating that aggregate parameters should be carefully considered. In a second part of the study, the selected aggregates were immobilized by encapsulation in methacrylamide-modified gelatin. Phenotype evaluations revealed that a stable hepatocyte phenotype could be maintained during 21 days when encapsulated in the hydrogel. In conclusion we have demonstrated the beneficial use of micro-well chips for hepatocyte aggregation and the size-dependent effects on hepatocyte phenotype. We also pointed out that methacrylamide-modified gelatin is suitable for the encapsulation of these aggregates. PMID- 25133501 TI - Sexually transmitted infection related stigma and shame among African American male youth: implications for testing practices, partner notification, and treatment. AB - A self-administered, street intercept survey was conducted in order to examine the relation of stigma and shame associated with sexually transmitted infections (STI) to STI testing practices, partner notification, and partner-delivered treatment among young African American men (n=108) in a low-income, urban community in San Francisco with high STI burden. Multivariate logistic regression revealed that increasing STI-related stigma was significantly associated with a decreased odds of STI testing, such that every standard deviation increase in stigma score was associated with 0.62 decreased odds of having been tested (aOR: 0.62, 95% CI: 0.38-1.00), controlling for age. STI stigma was also significantly associated with a decreased willingness to notify non-main partners of an STI (aOR: 0.64 95% CI: 0.41-0.99). Participants with higher levels of stigma and shame were also significantly less likely to be willing to deliver STI medication to a partner (stigma aOR: 0.57, 95% CI: 0.37-0.88; shame aOR 0.53 95% CI: 0.34 0.83). Findings suggest that STI-related stigma and shame, common in this population, could undermine STI testing, treatment, and partner notification programs. The medical establishment, one of the institutional factors to have reinforced this culture of stigma, must aid efforts to reduce its effects through providing integrated services, reframing sexual health in campaigns, educating clients, and providing wider options to aid disclosure and partner notification practices. PMID- 25133502 TI - Hospital-based program to increase child safety restraint use among birthing mothers in China. AB - OBJECTIVE: To evaluate a hospital-based educational program to increase child safety restraint knowledge and use among birthing mothers. METHODS: A prospective experimental and control study was performed in the Obstetrics department of hospitals. A total of 216 new birthing mothers from two hospitals (114 from intervention hospital and 102 from comparison hospital) were recruited and enrolled in the study. Intervention mothers received a height chart, an 8-minute video and a folded pamphlet regarding child safety restraint use during their hospital stay after giving birth. Evaluation data on the child safety seat (CSS) awareness, attitudes, and use were collected among both groups before and after the intervention. An additional phone interview was conducted among the intervention mothers two months after discharge. RESULTS: No significant differences existed between groups when comparing demographics. Over 90% of the intervention mothers found the educational intervention to be helpful to some extent. A significantly higher percentage of mothers in the intervention than the comparison group reported that CSS are necessary and are the safest seating practice. Nearly 20% of the intervention mothers actually purchased CSS for their babies after the intervention. While in both the intervention and comparison group, over 80% of mothers identified the ages of two through five as needing CSS, fewer than 50% of both groups identified infants as needing CSS, even after the intervention. CONCLUSION: The results indicated that child safety restraint education implemented in hospitals helps increase birthing mothers' overall knowledge and use of CSS. Further efforts are needed to address specific age related needs to promote car seats use among infants. PMID- 25133503 TI - Copy number variation analysis on a non-Hodgkin lymphoma case-control study identifies an 11q25 duplication associated with diffuse large B-cell lymphoma. AB - Recent GWAS have identified several susceptibility loci for NHL. Despite these successes, much of the heritable variation in NHL risk remains to be explained. Common copy-number variants are important genomic sources of variability, and hence a potential source to explain part of this missing heritability. In this study, we carried out a CNV analysis using GWAS data from 681 NHL cases and 749 controls to explore the relationship between common structural variation and lymphoma susceptibility. Here we found a novel association with diffuse large B cell lymphoma (DLBCL) risk involving a partial duplication of the C-terminus region of the LOC283177 long non-coding RNA that was further confirmed by quantitative PCR. For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), known somatic deletions were identified on chromosomes 13q14, 11q22 23, 14q32 and 22q11.22. Our study shows that GWAS data can be used to identify germline CNVs associated with disease risk for DLBCL and somatic CNVs for CLL/SLL. PMID- 25133504 TI - Pyrrolobenzodiazepines (PBDs) do not bind to DNA G-quadruplexes. AB - The pyrrolo[2,1-c][1,4] benzodiazepines (PBDs) are a family of sequence selective, minor-groove binding DNA-interactive agents that covalently attach to guanine residues. A recent publication in this journal (Raju et al, PloS One, 2012, 7, 4, e35920) reported that two PBD molecules were observed to bind with high affinity to the telomeric quadruplex of Tetrahymena glaucoma based on Electrospray Ionisation Mass Spectrometry (ESI-MS), Circular Dichroism, UV Visible and Fluorescence spectroscopy data. This was a surprising result given the close 3-dimensional shape match between the structure of all PBD molecules and the minor groove of duplex DNA, and the completely different 3-dimensional structure of quadruplex DNA. Therefore, we evaluated the interaction of eight PBD molecules of diverse structure with a range of parallel, antiparallel and mixed DNA quadruplexes using DNA Thermal Denaturation, Circular Dichroism and Molecular Dynamics Simulations. Those PBD molecules without large C8-substitutents had an insignificant affinity for the eight quadruplex types, although those with large pi-system-containing C8-substituents (as with the compounds evaluated by Raju and co-workers) were found to interact to some extent. Our molecular dynamics simulations support the likelihood that molecules of this type, including those examined by Raju and co-workers, interact with quadruplex DNA through their C8 substituents rather than the PBD moiety itself. It is important for the literature to be clear on this matter, as the mechanism of action of these agents will be under close scrutiny in the near future due to the growing number of PBD based agents entering the clinic as both single-agents and as components of antibody-drug conjugates (ADCs). PMID- 25133505 TI - The mutational spectrum of Lynch syndrome in cyprus. AB - Lynch syndrome is the most common form of hereditary colorectal cancer and is caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Mutation carriers have an increased lifetime risk of developing colorectal cancer as well as other extracolonic tumours. The aim of the current study was to evaluate the frequency and distribution of mutations in the MLH1, MSH2 and MSH6 genes within a cohort of Cypriot families that fulfilled the revised Bethesda guidelines. The study cohort included 77 patients who fulfilled at least one of the revised Bethesda guidelines. Mutational analysis revealed the presence of 4 pathogenic mutations, 3 in the MLH1 gene and 1 in the MSH2 gene, in 5 unrelated individuals. It is noted that out of the 4 pathogenic mutations detected, one is novel (c.1610delG in exon 14 of the MLH1) and has been detected for the first time in the Cypriot population. Overall, the pathogenic mutation detection rate in our patient cohort was 7%. This percentage is relatively low but could be explained by the fact that the sole criterion for genetic screening was compliance to the revised Bethesda guidelines. Larger numbers of Lynch syndrome families and screening of the two additional predisposition genes, PMS2 and EPCAM, are needed in order to decipher the full spectrum of mutations associated with Lynch syndrome predisposition in Cyprus. PMID- 25133506 TI - Consideration of sex in clinical trials of transdermal nicotine patch: a systematic review. AB - Transdermal nicotine patch (TNP) is 1 of the most commonly used smoking cessation treatments; however, the efficacy of TNP by sex is not yet clear. The purpose of the current review was to synthesize how sex has been considered in published clinical trials of TNP for smoking cessation. The specific aims of the study were to examine the inclusion of sex in analyses of cessation outcomes, TNP-related variables (compliance, side effects), and quit-related variables (withdrawal, cravings); to review the consideration of sex-related variables (menstrual cycle phase, pregnancy); and to identify needs for future research. Potential articles published through December 31, 2013 were identified through a MEDLINE search of the terms "clinical trial," "nicotine patch," and "smoking cessation." Forty-two studies used all 3 terms and met the inclusion criteria. Approximately half of the studies reported that they considered sex in smoking cessation outcomes, with 15 studies finding no difference by sex and 7 studies finding better outcomes for men versus women. Only 5 studies reported data on outcomes by sex in their publications. No studies reported analysis of TNP compliance or withdrawal by sex. In the 1 study that examined side effects by sex, more women than men reported discontinuing TNP because of skin irritation. No study examined the association of cessation outcomes with menstrual cycle phase. There is a need to include sex in research on TNP, as well as other pharmacological and behavioral smoking treatments, to clarify the picture of treatment efficacy for women compared with men. PMID- 25133509 TI - MCP/CCR2 signaling is essential for recruitment of mesenchymal progenitor cells during the early phase of fracture healing. AB - OBJECTIVE: The purpose of this study was to investigate chemokine profiles and their functional roles in the early phase of fracture healing in mouse models. METHODS: The expression profiles of chemokines were examined during fracture healing in wild-type (WT) mice using a polymerase chain reaction array and histological staining. The functional effect of monocyte chemotactic protein-1 (MCP-1) on primary mouse bone marrow stromal cells (mBMSCs) was evaluated using an in vitro migration assay. MCP-1-/- and C-C chemokine receptor 2 (CCR2)-/- mice were fractured and evaluated by histological staining and micro-computed tomography (micro-CT). RS102895, an antagonist of CCR2, was continuously administered in WT mice before or after rib fracture and evaluated by histological staining and micro-CT. Bone graft exchange models were created in WT and MCP-1-/- mice and were evaluated by histological staining and micro-CT. RESULTS: MCP-1 and MCP-3 expression in the early phase of fracture healing were up-regulated, and high levels of MCP-1 and MCP-3 protein expression observed in the periosteum and endosteum in the same period. MCP-1, but not MCP-3, increased migration of mBMSCs in a dose-dependent manner. Fracture healing in MCP-1-/- and CCR2-/- mice was delayed compared with WT mice on day 21. Administration of RS102895 in the early, but not in the late phase, caused delayed fracture healing. Transplantation of WT-derived graft into host MCP-1-/- mice significantly increased new bone formation in the bone graft exchange models. Furthermore, marked induction of MCP-1 expression in the periosteum and endosteum was observed around the WT-derived graft in the host MCP-1-/- mouse. Conversely, transplantation of MCP-1-/- mouse-derived grafts into host WT mice markedly decreased new bone formation. CONCLUSIONS: MCP-1/CCR2 signaling in the periosteum and endosteum is essential for the recruitment of mesenchymal progenitor cells in the early phase of fracture healing. PMID- 25133510 TI - Prognostic value of red blood cell distribution width for patients with heart failure: a systematic review and meta-analysis of cohort studies. AB - AIMS: Multiple studies have investigated the prognostic role of red blood cell distribution width (RDW) for patients with heart failure (HF), but the results have been inconsistent. The aim of the present study was to estimate the impact of RDW on the prognosis of HF by performing a systematic review and meta analysis. METHODS AND RESULTS: The Embase, PubMed, and Web of Science databases were searched up to November 16, 2013 to identify eligible cohort studies. The quality of each study was assessed using the Newcastle-Ottawa Scale (NOS). The association between RDW, either on admission or at discharge, and HF outcomes (all-cause mortality [ACM], heart transplantation, cardiovascular mortality, and rehospitalization, etc.) were reviewed. The overall hazard ratio (HR) for the effect of RDW on ACM was pooled using a random-effects model, and the publication bias was evaluated using funnel plots and Eggers' tests. Seventeen studies, with a total of 18288 HF patients, were included for systematic review. All eligible studies indicated that RDW on admission and RDW at discharge, as well as its change during treatment, were of prognostic significance for HF patients. The HR for the effect of a 1% increase in baseline RDW on ACM was 1.10 (95% confidence interval: 1.07-1.13), based on pooling of nine studies that provided related data. However, publication bias was observed among these studies. CONCLUSIONS: HF patients with higher RDW may have poorer prognosis than those with lower RDW. Further studies are needed to explore the potential mechanisms underlying this association. PMID- 25133511 TI - Insulin, CCAAT/enhancer-binding proteins and lactate regulate the human 11beta hydroxysteroid dehydrogenase type 2 gene expression in colon cancer cell lines. AB - 11beta-Hydroxysteroid dehydrogenases (11beta-HSD) modulate mineralocorticoid receptor transactivation by glucocorticoids and regulate access to the glucocorticoid receptor. The isozyme 11beta-HSD2 is selectively expressed in mineralocorticoid target tissues and its activity is reduced in various disease states with abnormal sodium retention and hypertension, including the apparent mineralocorticoid excess. As 50% of patients with essential hypertension are insulin resistant and hyperinsulinemic, we hypothesized that insulin downregulates the 11beta-HSD2 activity. In the present study we show that insulin reduced the 11beta-HSD2 activity in cancer colon cell lines (HCT116, SW620 and HT 29) at the transcriptional level, in a time and dose dependent manner. The downregulation was reversible and required new protein synthesis. Pathway analysis using mRNA profiling revealed that insulin treatment modified the expression of the transcription factor family C/EBPs (CCAAT/enhancer-binding proteins) but also of glycolysis related enzymes. Western blot and real time PCR confirmed an upregulation of C/EBP beta isoforms (LAP and LIP) with a more pronounced increase in the inhibitory isoform LIP. EMSA and reporter gene assays demonstrated the role of C/EBP beta isoforms in HSD11B2 gene expression regulation. In addition, secretion of lactate, a byproduct of glycolysis, was shown to mediate insulin-dependent HSD11B2 downregulation. In summary, we demonstrate that insulin downregulates HSD11B2 through increased LIP expression and augmented lactate secretion. Such mechanisms are of interest and potential significance for sodium reabsorption in the colon. PMID- 25133512 TI - Multivariable logistic regression model: a novel mathematical model that predicts visual field sensitivity from macular ganglion cell complex thickness in glaucoma. AB - PURPOSE: To design a mathematical model that can predict the relationship between the ganglion cell complex (GCC) thickness and visual field sensitivity (VFS) in glaucoma patients. DESIGN: Retrospective cross-sectional case series. METHOD: Within 3 months from VFS measurements by the Humphrey field analyzer 10-2 program, 83 eyes underwent macular GCC thickness measurements by spectral-domain optical coherence tomography (SD-OCT). Data were used to construct a multiple logistic model that depicted the relationship between the explanatory variables (GCC thickness, age, sex, and spherical equivalent of refractive errors) determined by a regression analysis and the mean VFS corresponding to the SD-OCT scanned area. Analyses were performed in half or 8 segmented local areas as well as in whole scanned areas. A simple logistic model that included GCC thickness as the single explanatory variable was also constructed. The ability of the logistic models to depict the real GCC thickness/VFS in SAP distribution was analyzed by the chi2 test of goodness-of-fit. The significance of the model effect was analyzed by analysis of variance (ANOVA). RESULTS: Scatter plots between the GCC thickness and the mean VFS showed sigmoid curves. The chi2 test of goodness-of fit revealed that the multiple logistic models showed a good fit for the real GCC thickness/VFS distribution in all areas except the nasal-inferior-outer area. ANOVA revealed that all of the multiple logistic models significantly predicted the VFS based on the explanatory variables. Although simple logistic models also exhibited significant VFS predictability based on the GCC thickness, the model effect was less than that observed for the multiple logistic models. CONCLUSIONS: The currently proposed logistic models are useful methods for depicting relationships between the explanatory variables, including the GCC thickness, and the mean VFS in glaucoma patients. PMID- 25133514 TI - "The mask who wasn't there": visual masking effect with the perceptual absence of the mask. AB - Does a visual mask need to be perceptually present to disrupt processing? In the present research, we proposed to explore the link between perceptual and memory mechanisms by demonstrating that a typical sensory phenomenon (visual masking) can be replicated at a memory level. Experiment 1 highlighted an interference effect of a visual mask on the categorization of auditory targets and confirmed the multimodal nature of knowledge. In Experiment 2, we proposed to reactivate this mask in a categorization task on visual targets. Results showed that the sensory mask has disrupted (slower reaction times) the processing of the targets whether the mask was perceptually present or reactivated in memory. These results support a sensory-based conception of memory processing and suggest that the difference between perceptual processes and memory processes is characterized by the presence (perception) or the absence (memory) of the sensory properties involved in the activity. PMID- 25133513 TI - Identification and functional analysis of pheromone and receptor genes in the B3 mating locus of Pleurotus eryngii. AB - Pleurotus eryngii has recently become a major cultivated mushroom; it uses tetrapolar heterothallism as a part of its reproductive process. Sexual development progresses only when the A and B mating types are compatible. Such mating incompatibility occasionally limits the efficiency of breeding programs in which crossing within loci-shared strains or backcrossing strategies are employed. Therefore, understanding the mating system in edible mushroom fungi will help provide a short cut in the development of new strains. We isolated and identified pheromone and receptor genes in the B3 locus of P. eryngii and performed a functional analysis of the genes in the mating process by transformation. A genomic DNA library was constructed to map the entire mating type locus. The B3 locus was found to contain four pheromone precursor genes and four receptor genes. Remarkably, receptor PESTE3.3.1 has just 34 amino acid residues in its C-terminal cytoplasmic region; therefore, it seems likely to be a receptor-like gene. Real-time quantitative RT-PCR (real-time qRT-PCR) revealed that most pheromone and receptor genes showed significantly higher expression in monokaryotic cells than dikaryotic cells. The pheromone genes PEphb3.1 and PEphb3.3 and the receptor gene PESTE3.3.1 were transformed into P5 (A3B4). The transformants were mated with a tester strain (A4B4), and the progeny showed clamp connections and a normal fruiting body, which indicates the proposed role of these genes in mating and fruiting processes. This result also confirms that PESTE3.3.1 is a receptor gene. In this study, we identified pheromone and receptor genes in the B3 locus of P. eryngii and found that some of those genes appear to play a role in the mating and fruiting processes. These results might help elucidate the mechanism of fruiting differentiation and improve breeding efficiency. PMID- 25133515 TI - The efficacy of self-paced study in multitrial learning. AB - In 2 experiments we investigated the efficacy of self-paced study in multitrial learning. In Experiment 1, native speakers of English studied lists of Dutch English word pairs under 1 of 4 imposed fixed presentation rate conditions (24 * 1 s, 12 * 2 s, 6 * 4 s, or 3 * 8 s) and a self-paced study condition. Total study time per list was equated for all conditions. We found that self-paced study resulted in better recall performance than did most of the fixed presentation rates, with the exception of the 12 * 2 s condition, which did not differ from the self-paced condition. Additional correlational analyses suggested that the allocation of more study time to difficult pairs than to easy pairs might be a beneficial strategy for self-paced learning. Experiment 2 was designed to test this hypothesis. In 1 condition, participants studied word pairs in a self-paced fashion without any restrictions. In the other condition, participants studied word pairs in a self-paced fashion but total study time per item was equated. The results showed that allowing self-paced learners to freely allocate study time over items resulted in better recall performance. PMID- 25133516 TI - Indanthrone dye revisited after sixty years. AB - Indanthrone, an old, insoluble dye can be converted into a solution processable, self-assembling and electroluminescent organic semiconductor, namely tetraoctyloxydinaptho[2,3-a:2',3'-h]phenazine (P-C8), in a simple one-pot process consisting of the reduction of the carbonyl group by sodium dithionite followed by the substitution with solubility inducing groups under phase transfer catalysis conditions. PMID- 25133517 TI - Scorpions: a presentation. AB - Scorpions, at least the species of the family Buthidae whose venoms are better known, appear as animals that have evolved very little over time. The composition of their venoms is relatively simple as most toxins have a common structural motif that is found in other venoms from primitive species. Moreover, all the scorpion venom toxins principally act on membrane ionic channels of excitable cells. The results of recent works lead to the conclusion that in scorpions there is a close relationship between venomous function and innate immune function both remarkably efficient. PMID- 25133518 TI - Solid-state NMR analysis of a complex crystalline phase of ronacaleret hydrochloride. AB - A crystalline phase of the pharmaceutical compound ronacaleret hydrochloride is studied by solid-state nuclear magnetic resonance (SSNMR) spectroscopy and single crystal X-ray diffraction. The crystal structure is determined to contain two independent cationic molecules and chloride anions in the asymmetric unit, which combine with the covalent structure of the molecule to yield complex SSNMR spectra. Experimental approaches based on dipolar correlation, chemical shift tensor analysis, and quadrupolar interaction analysis are employed to obtain detailed information about this phase. Density functional theory (DFT) calculations are used to predict chemical shielding and electric field gradient (EFG) parameters for comparison with experiment. (1)H SSNMR experiments performed at 16.4 T using magic-angle spinning (MAS) and homonuclear dipolar decoupling provide information about hydrogen bonding and molecular connectivity that can be related to the crystal structure. (19)F and (13)C assignments for the Z' = 2 structure are obtained using DFT calculations, (19)F homonuclear dipolar correlation, and (13)C-(19)F heteronuclear dipolar correlation experiments. (35)Cl MAS experiments at 16.4 T observe two chlorine sites that are assigned using calculated chemical shielding and EFG parameters. SSNMR dipolar correlation experiments are used to extract (1)H-(13)C, (1)H-(15)N, (1)H-(19)F, (13)C-(19)F, and (1)H-(35)Cl through-space connectivity information for many positions of interest. The results allow for the evaluation of the performance of a suite of SSNMR experiments and computational approaches as applied to a complex but typical pharmaceutical solid phase. PMID- 25133519 TI - Effects of Acute Active Video Games on Endothelial Function Following a High-Fat Meal in Overweight Adolescents. AB - BACKGROUND: We tested the hypothesis that an active video game following a high fat meal would partially prevent the unfavorable effect of a high-fat meal on vascular function in overweight adolescents. METHODS: Twenty-four overweight adolescents were randomized to either a 60-minute active video game (AVG) group (n = 12) or seated rest (SR) as a control group (n = 12) after a high-fat meal. Blood parameters were measured, and vascular function was measured using brachial artery flow-mediated dilation (FMD) at baseline and 3 hours after a high-fat meal. RESULTS: No significant interaction was found in any blood parameter. A high-fat meal significantly increased blood triglyceride and glucose concentrations in both groups in a similar manner. Brachial artery FMD significantly decreased in the SR group (13.8 +/- 3.2% to 11.8 +/- 2.5), but increased in the AVG group (11.4 +/- 4.0% to 13.3 +/- 3.5), with a significant interaction (P = .034). CONCLUSION: These findings show that an active video game attenuated high-fat meal-induced endothelial dysfunction. This suggests that an active video game may have a cardioprotective effect on endothelial function in overweight adolescents when exposed to a high-fat meal. PMID- 25133520 TI - Molecular and phytochemical investigation of Angelica dahurica and Angelica pubescentis essential oils and their biological activity against Aedes aegypti, Stephanitis pyrioides, and Colletotrichum species. AB - In this study, Angelica dahurica and Angelica pubescentis root essential oils were investigated as pest management perspectives, and root samples were also analyzed genetically using the nuclear ribosomal internal transcribed spacer (ITS) region as a DNA barcode marker. A. pubescentis root essential oil demonstrated weak antifungal activity against Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides, whereas A. dahurica root essential oil did not show antifungal activity. Conversely, A. dahurica root essential oil demonstrated better biting deterrent and insecticidal activity against yellow fever mosquito, Aedes aegypti, and azalea lace bugs, Stephanitis pyrioides, than A. pubescentis root oil. The major compounds in the A. dahurica oil were found as alpha-pinene (46.3%), sabinene (9.3%), myrcene (5.5%), 1 dodecanol (5.2%), and terpinen-4-ol (4.9%). alpha-Pinene (37.6%), p-cymene (11.6%), limonene (8.7%), and cryptone (6.7%) were the major compounds found in the A. pubescentis oil. In mosquito bioassays, 1-dodecanol and 1-tridecanol showed antibiting deterrent activity similar to the positive control DEET (N,N diethyl-3-methylbenzamide) at 25 nmol/cm(2) against Ae. aegypti, whereas only 1 tridecanol showed repellent activity in human-based cloth patch bioassay with minimum effective dosages (MED) of 0.086 +/- 0.089 mg/cm(2) (DEET = 0.007 +/- 0.003 mg/cm(2)). In larval bioassays, 1-tridecanol was more toxic with an LC50 value of 2.1 ppm than 1-dodecanol having an LC50 value of 5.2 ppm against 1-day old Ae. aegypti larvae. 1-Dodecanol and 1-tridecanol could be useful for the natural mosquito control agents. PMID- 25133521 TI - V-shaped bis-coumarins: synthesis and optical properties. AB - A highly efficient procedure for the synthesis of bis-coumarins fused at the pyranone ring has been developed. The electron-rich phenols reacted with esters of coumarin-3-carboxylic acids, leading to substituted chromeno[3,4-c]chromene 6,7-diones. The reaction is catalyzed by both Lewis acids and 4 dimethylaminopyridine. The most probable mechanistic pathway involves Lewis acid catalyzed or DMAP catalyzed transesterification, followed by intramolecular conjugate addition of alpha,beta-unsaturated esters to phenols and subsequent oxidation of the initially formed intermediate. The reaction is compatible with various functionalities such as NO2, Br, and OMe. Not only benzene derivatives but also dihydroxynaphthalenes are reactive in this reaction, and the structure of the product can be controlled by adjusting the reaction conditions. Furthermore, a double addition is possible, leading to a horseshoe-shaped system comprised of seven conjugated rings. Compounds with four structurally unique skeletons have been obtained and have been shown to strongly absorb in the violet, blue, and/or green regions of the visible spectrum. Most of them display strong greenish yellow fluorescence, which can be modulated by both structural changes and the character of the solvents. Again, introduction of an electron donating group in the chromeno[3,4-c]chromene-6,7-diones caused a significant red shift in both the absorption and emission maxima, and the effect became especially noteworthy in the case of amino substituents. PMID- 25133523 TI - Nonstoichiometric nucleation and growth of multicomponent nanocrystals in solution. AB - The ability to assemble nanoscale functional building blocks is a useful and modular way for scientists to design valuable materials with specific physical and chemical properties. Chemists expect multicomponent, heterostructured nanocrystals to show unique electrical, thermal, and optical properties not seen in homogeneous, single-phase nanocrystals. Although researchers have made remarkable advances in heterogeneous nucleation and growth, design of synthetic conditions for obtaining nanocrystals with a target composition and shape is still a big challenge. There are several outstanding issues that chemists need to address before they can successfully carry out the design-based synthesis of multicomponent nanocrystals. For instance, small changes in the reaction parameters, such as the precursor, solvent, surfactant, reducing agent, and the reaction temperature, often result in changes in the structure and chemical composition of the final product. Although scientists do not fully understand the mechanisms underlying the nucleation and growth processes involved in the synthesis of these multicomponent nanocrystals, recent progress in understanding of the thermodynamic and kinetic factors have improved our control over their final structure and chemical composition. In this Account, we summarize our recent advances in understanding of the nucleation and growth mechanisms involved in the solution-based synthesis of multicomponent nanocrystals. We also discuss the various challenges encountered in their synthesis, emphasizing what still needs special consideration. We first discuss the three different nucleation paths from a thermodynamics perspective: amorphous nucleation, crystalline nucleation, and two-step nucleation. Amorphous nucleation and two-step nucleation involve the generation of nonstoichiometric nuclei. We initiate this process mainly by introducing an imbalance in the concentrations of the reduced elements. When the nonstoichiometric nuclei grow, we can add secondary elements to the growing nonstoichiometric nuclei. This leads to either the physical deposition or atomic mixture formation through the diffusion and rearrangement of constituents. The processes of mixture formation and the physical deposition of the secondary constituent element also compete and determine the shape and chemical composition of the final product. If the free energy change by mixture formation is positive (DeltaGAB >= 0), physical deposition takes place predominantly, and the spreading coefficient (S) determines the structure of the nanocrystals. However, when mixture formation is highly spontaneous (DeltaGAB < -xi), the chemical composition of the final product is usually stoichiometric, and its shape then depends on the size of the primary nanocrystals. When the mixture formation and physical deposition are in competition (-xi <= DeltaGAB < 0), as commonly seen for many nanoalloy systems, both the chemical composition and the structure are determined by the size of the primary nanocrystals as well as the degree of mixture formation at the interface of the constituent components. Finally, we discuss the challenges and caveats that one needs to take into account when synthesizing multicomponent nanocrystals. PMID- 25133524 TI - Team-based surgical care: an important role for academic health centers. PMID- 25133522 TI - Promises and pitfalls of intracellular delivery of proteins. AB - The direct delivery of functional proteins into the cell cytosol is a key issue for protein therapy, with many current strategies resulting in endosomal entrapment. Protein delivery to the cytosol is challenging due to the high molecular weight and the polarity of therapeutic proteins. Here we review strategies for the delivery of proteins into cells, including cell-penetrating peptides, virus-like particles, supercharged proteins, nanocarriers, polymers, and nanoparticle-stabilized nanocapsules. The advantages and disadvantages of these approaches including cytosolar delivery are compared and contrasted, with promising pathways forward identified. PMID- 25133525 TI - Surface coating mediated swelling and fracture of silicon nanowires during lithiation. AB - Surface passivation of silicon anodes is an appealing design strategy for the development of reliable, high-capacity lithium-ion batteries. However, the structural stability of the coating layer and its influence on the lithiation process remain largely unclear. Herein, we show that surface coating mediates the swelling dynamics and the fracture pattern during initial lithiation of crystalline silicon nanopillars. We choose conformally nickel coated silicon architectures as a model system. Experimental findings are interpreted based on a chemomechanical model. Markedly different swelling and fracture regimes have been identified, depending on the coating thickness and silicon nanopillar diameter. Nanopillars with relatively thin coating display anisotropic swelling similar to pristine nanopillars, but with different preferred fracture sites. As the coating thickness increases, the mechanisms become isotropic, with one randomly oriented longitudinal crack that unzips the core-shell structure. The morphology of cracked pillars resembles that of a thin-film electrode on a substrate, which is more amenable to cyclic lithiation without fracture. The knowledge provided here helps clarify the cycling results of coated nanosilicon electrodes and further suggests design rules for better performance electrodes through proper control of the lithiation and fracture. PMID- 25133526 TI - Systematic genetic analysis identifies Cis-eQTL target genes associated with glioblastoma patient survival. AB - Prior expression quantitative trait locus (eQTL) studies have demonstrated heritable variation determining differences in gene expression. The majority of eQTL studies were based on cell lines and normal tissues. We performed cis-eQTL analysis using glioblastoma multiforme (GBM) data sets obtained from The Cancer Genome Atlas (TCGA) to systematically investigate germline variation's contribution to tumor gene expression levels. We identified 985 significant cis eQTL associations (FDR<0.05) mapped to 978 SNP loci and 159 unique genes. Approximately 57% of these eQTLs have been previously linked to the gene expression in cell lines and normal tissues; 43% of these share cis associations known to be associated with functional annotations. About 25% of these cis-eQTL associations are also common to those identified in Breast Cancer from a recent study. Further investigation of the relationship between gene expression and patient clinical information identified 13 eQTL genes whose expression level significantly correlates with GBM patient survival (p<0.05). Most of these genes are also differentially expressed in tumor samples and organ-specific controls (p<0.05). Our results demonstrated a significant relationship of germline variation with gene expression levels in GBM. The identification of eQTLs-based expression associated survival might be important to the understanding of genetic contribution to GBM cancer prognosis. PMID- 25133527 TI - Characterization of the SUMO-binding activity of the myeloproliferative and mental retardation (MYM)-type zinc fingers in ZNF261 and ZNF198. AB - SUMO-binding proteins interact with SUMO modified proteins to mediate a wide range of functional consequences. Here, we report the identification of a new SUMO-binding protein, ZNF261. Four human proteins including ZNF261, ZNF198, ZNF262, and ZNF258 contain a stretch of tandem zinc fingers called myeloproliferative and mental retardation (MYM)-type zinc fingers. We demonstrated that MYM-type zinc fingers from ZNF261 and ZNF198 are necessary and sufficient for SUMO-binding and that individual MYM-type zinc fingers function as SUMO-interacting motifs (SIMs). Our binding studies revealed that the MYM-type zinc fingers from ZNF261 and ZNF198 interact with the same surface on SUMO-2 recognized by the archetypal consensus SIM. We also present evidence that MYM type zinc fingers in ZNF261 contain zinc, but that zinc is not required for SUMO binding. Immunofluorescence microscopy studies using truncated fragments of ZNF198 revealed that MYM-type zinc fingers of ZNF198 are necessary for localization to PML-nuclear bodies (PML-NBs). In summary, our studies have identified and characterized the SUMO-binding activity of the MYM-type zinc fingers in ZNF261 and ZNF198. PMID- 25133528 TI - A method to evaluate genome-wide methylation in archival formalin-fixed, paraffin embedded ovarian epithelial cells. AB - BACKGROUND: The use of DNA from archival formalin and paraffin embedded (FFPE) tissue for genetic and epigenetic analyses may be problematic, since the DNA is often degraded and only limited amounts may be available. Thus, it is currently not known whether genome-wide methylation can be reliably assessed in DNA from archival FFPE tissue. METHODOLOGY/PRINCIPAL FINDINGS: Ovarian tissues, which were obtained and formalin-fixed and paraffin-embedded in either 1999 or 2011, were sectioned and stained with hematoxylin-eosin (H&E).Epithelial cells were captured by laser micro dissection, and their DNA subjected to whole genomic bisulfite conversion, whole genomic polymerase chain reaction (PCR) amplification, and purification. Sequencing and software analyses were performed to identify the extent of genomic methylation. We observed that 31.7% of sequence reads from the DNA in the 1999 archival FFPE tissue, and 70.6% of the reads from the 2011 sample, could be matched with the genome. Methylation rates of CpG on the Watson and Crick strands were 32.2% and 45.5%, respectively, in the 1999 sample, and 65.1% and 42.7% in the 2011 sample. CONCLUSIONS/SIGNIFICANCE: We have developed an efficient method that allows DNA methylation to be assessed in archival FFPE tissue samples. PMID- 25133532 TI - MALDI-guided SIMS: multiscale imaging of metabolites in bacterial biofilms. AB - Mass spectrometry imaging (MSI) is a versatile tool for visualizing molecular distributions in complex biological specimens, but locating microscopic chemical features of interest can be challenging in samples that lack a well-defined anatomy. To address this issue, we developed a correlated imaging approach that begins with performing matrix-assisted laser desorption/ionization (MALDI) MSI to obtain low-resolution molecular maps of a sample. The resulting maps are then used to direct subsequent microscopic secondary ion mass spectrometry (SIMS) imaging and tandem mass spectrometry (MS/MS) experiments to examine selected chemical regions of interest. By employing MALDI undersampling, the sample surface is left mostly unperturbed and available for the SIMS analysis, while also generating an ablation array that can be used for navigation in SIMS. We validated this MALDI-guided SIMS approach using cultured biofilms of the opportunistic pathogen Pseudomonas aeruginosa; bioactive secondary metabolites, including rhamnolipids and quinolones, were detected and visualized on both macro and microscopic size scales. MSI mass assignments were confirmed with in situ MALDI MS/MS and capillary electrophoresis-electrospray ionization MS/MS analysis of biofilm extracts. Two strains of P. aeruginosa were compared, wild type and a quorum sensing mutant, and differences in metabolite abundance and distribution were observed. PMID- 25133529 TI - Global metabolomic analysis of human saliva and plasma from healthy and diabetic subjects, with and without periodontal disease. AB - Recent studies suggest that periodontal disease and type 2 diabetes mellitus are bi-directionally associated. Identification of a molecular signature for periodontitis using unbiased metabolic profiling could allow identification of biomarkers to assist in the diagnosis and monitoring of both diabetes and periodontal disease. This cross-sectional study identified plasma and salivary metabolic products associated with periodontitis and/or diabetes in order to discover biomarkers that may differentiate or demonstrate an interaction of these diseases. Saliva and plasma samples were analyzed from 161 diabetic and non diabetic human subjects with a healthy periodontium, gingivitis and periodontitis. Metabolite profiling was performed using Metabolon's platform technology. A total of 772 metabolites were found in plasma and 475 in saliva. Diabetics had significantly higher levels of glucose and alpha-hydroxybutyrate, the established markers of diabetes, for all periodontal groups of subjects. Comparison of healthy, gingivitis and periodontitis saliva samples within the non diabetic group confirmed findings from previous studies that included increased levels of markers of cellular energetic stress, increased purine degradation and glutathione metabolism through increased levels of oxidized glutathione and cysteine-glutathione disulfide, markers of oxidative stress, including increased purine degradation metabolites (e.g. guanosine and inosine), increased amino acid levels suggesting protein degradation, and increased omega-3 (docosapentaenoate) and omega-6 fatty acid (linoleate and arachidonate) signatures. Differences in saliva between diabetic and non-diabetic cohorts showed altered signatures of carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global untargeted metabolic profiling of human saliva in diabetics replicated the metabolite signature of periodontal disease progression in non-diabetic patients and revealed unique metabolic signatures associated with periodontal disease in diabetics. The metabolites identified in this study that discriminated the periodontal groups may be useful for developing diagnostics and therapeutics tailored to the diabetic population. PMID- 25133533 TI - Peripheral arterial disease among adult diabetic patients attending a large outpatient diabetic clinic at a national referral hospital in Uganda: a descriptive cross sectional study. AB - BACKGROUND: Peripheral arterial disease (PAD) is one of the recognised diabetic macro vascular complications. It is a marker of generalised systemic atherosclerosis and is closely associated with symptomatic coronary and cerebrovascular disease, hence significant morbidity and mortality. Among African adult diabetic populations, screening and diagnosis of PAD is frequently suboptimal. The aim of this study was to determine the prevalence and associated clinical factors of PAD in adult ambulatory diabetic patients attending the outpatient diabetic clinic of Mulago national referral and teaching hospital, Kampala Uganda. METHODS: In this descriptive cross sectional study, 146 ambulatory adult diabetic patients were studied. Information about their socio demographic and clinical characteristics, fasting lipid profile status, blood pressure, glycated haemoglobin (HbA1c) levels and presence of albuminuria was collected using a pre tested questionnaire. Measurement of ankle brachial index (ABI) to assess for PAD, defined as a ratio less than 0.9 was performed using a portable 5-10 MHz Doppler device. Clinical factors associated with PAD were determined by comparing specific selected characteristics in patients with PAD and those without. RESULTS: The mean age/standard deviation of the study participants was 53.9/12.4 years with a male predominance (75, 51.4%). PAD was prevalent in 57 (39%) study participants. Of these, 34 (59.6%) had symptomatic PAD. The noted clinical factors associated with PAD in this study population were presence of symptoms of intermittent claudication and microalbuminuria. CONCLUSIONS: This study documents a high prevalence of PAD among adult ambulatory Ugandan diabetic patients. Aggressive screening for PAD using ABI measurement in adult diabetic patients should be emphasised in Uganda especially in the presence of symptoms of intermittent claudication and microalbuminuria. PMID- 25133534 TI - Breast contrast-enhanced ultrasound: is a scoring system feasible? A preliminary study in China. AB - OBJECTIVES: Although many studies about breast contrast-enhanced ultrasound had been conducted, clear diagnostic criteria for evaluating enhancement patterns are still lacking. This study aims to identify significant indicators for breast contrast-enhanced ultrasound and to establish an initial scoring system. MATERIALS AND METHODS: Totally 839 patients were included in the study. This study was divided into two parts. 364 patients were included in part 1 while 475 in part 2. Conventional ultrasound and contrast-enhanced ultrasound were used to examine each lesion. Only the cases in part 2 were also examined by elastography. In part 1, Logistic regression analysis was performed to predict significant variables. A 5-point scoring system was developed based on the results. In part 2, the scoring system was used to evaluate all the breast lesions. To evaluate the diagnostic efficacy of the new scoring system, it was compared with the system established for elastography and conventional ultrasound (BI-RADS). RESULTS: Three independent variables, namely, lesion scope, margin, and shape were selected in the final step of the logistic regression analysis in part 1. In part 2, the area under the ROC (receiver operating characteristic) curve for the contrast-enhanced scoring system was 0.912. The difference in the diagnostic capabilities of the contrast-enhanced scoring system and elastography was not statistically significant (P = 0.17). The difference in the diagnostic capabilities of the contrast-enhanced scoring system and BI-RADS was statistically significant (P<0.001). CONCLUSIONS: The contrast-enhanced patterns of benign and malignant breast tumors are different. The application of a 5-point scoring system for contrast-enhanced ultrasound is clinically promising. PMID- 25133537 TI - Venous thromboembolism prophylaxis for medical patients: who needs it? PMID- 25133535 TI - Habitual functional electrical stimulation therapy improves gait kinematics and walking performance, but not patient-reported functional outcomes, of people with multiple sclerosis who present with foot-drop. AB - BACKGROUND: People with Multiple Sclerosis (pwMS) often experience a disturbed gait function such as foot-drop. The objective of this pilot study was to investigate the medium term effects of using Functional Electrical Stimulation (FES) to treat foot-drop over a period 12 weeks on gait and patient reported outcomes of pwMS. METHODS AND FINDINGS: Nine pwMS aged 35 to 64 (2 males, 7 females) were assessed on four occasions; four weeks before baseline, at baseline and after six weeks and twelve weeks of FES use. Joint kinematics and performance on the 10 meter and 2 minute walk tests (10WT, 2 minWT) were assessed with and without FES. Participants also completed the MS walking Scale (MSWS), MS impact scale (MSIS29), Fatigue Severity Score (FSS) and wore an activity monitor for seven days after each assessment. Compared to unassisted walking, FES resulted in statistically significant improvements in peak dorsiflexion in swing (p = 0.006), 10MWT (p = 0.006) and 2 minWT (p = 0.002). Effect sizes for the training effect, defined as the change from unassisted walking at baseline to that at 12 weeks, indicated improved ankle angle at initial contact (2.6 degrees , 95% CI -1 degrees to 4 degrees , d = 0.78), and a decrease in perceived exertion over the 2 min walking tests (-1.2 points, 95% CI -5.7 to 3.4, d = -0.86). Five participants exceeded the Minimally Detectable Change (MDC) for a training effect on the 10mWT, but only two did so for the 2 minWT. No effects of the use of FES for 12 weeks were found for MSWS, MSIS29, FSS or step count. CONCLUSION: Although FES to treat foot-drop appears to offer the potential for a medium term training effect on ankle kinematics and walking speed, this was not reflected in the patient reported outcomes. This observed lack of relationship between objective walking performance and patient reported outcomes warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01977287. PMID- 25133536 TI - CSF and blood oxytocin concentration changes following intranasal delivery in macaque. AB - Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels. PMID- 25133539 TI - Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt. AB - Pulmonary arterial hypertension (PH) is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT)-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK) phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt) pathway and nuclear factor (NF)-kappaB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine induced neutrophil chemoattractant (CINC)-1, CINC-2alpha/beta, tissue inhibitor of metalloproteinase (TIMP)-1, interleukin (IL)-1alpha, lipopolysaccharide induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-1alpha, and MIP-3alpha. NF-kappaB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension. PMID- 25133540 TI - Redox-sensitive induction of Src/PI3-kinase/Akt and MAPKs pathways activate eNOS in response to EPA:DHA 6:1. AB - AIMS: Omega-3 fatty acid products containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have vasoprotective effects, in part, by stimulating the endothelial formation of nitric oxide (NO). This study determined the role of the EPA:DHA ratio and amount, and characterized the mechanism leading to endothelial NO synthase (eNOS) activation. METHODS AND RESULTS: EPA:DHA 6?1 and 9?1 caused significantly greater endothelium-dependent relaxations in porcine coronary artery rings than EPA:DHA 3?1, 1?1, 1?3, 1?6, 1?9, EPA and DHA alone, and EPA:DHA 6?1 with a reduced EPA + DHA amount, which were inhibited by an eNOS inhibitor. Relaxations to EPA:DHA 6?1 were insensitive to cyclooxygenase inhibition, and reduced by inhibitors of either oxidative stress, Src kinase, PI3 kinase, p38 MAPK, MEK, or JNK. EPA:DHA 6?1 induced phosphorylation of Src, Akt, p38 MAPK, ERK, JNK and eNOS; these effects were inhibited by MnTMPyP. EPA:DHA 6?1 induced the endothelial formation of ROS in coronary artery sections as assessed by dihydroethidium, and of superoxide anions and hydrogen peroxide in cultured endothelial cells as assessed by electron spin resonance with the spin probe CMH, and the Amplex Red based assay, respectively. CONCLUSION: Omega-3 fatty acids cause endothelium-dependent NO-mediated relaxations in coronary artery rings, which are dependent on the EPA:DHA ratio and amount, and involve an intracellular activation of the redox-sensitive PI3-kinase/Akt and MAPKs pathways to activate eNOS. PMID- 25133541 TI - Osteopontin is expressed in the mouse uterus during early pregnancy and promotes mouse blastocyst attachment and invasion in vitro. AB - Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. OPN mRNA and proteins are induced by in vivo and in vitro decidualization. OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion. PMID- 25133542 TI - Coptidis rhizome and Si Jun Zi Tang can prevent Salmonella enterica serovar Typhimurium infection in mice. AB - Salmonella, a common zoonotic pathogen, causes gastroenteritis in both humans and animals. Traditional Chinese Medicine (TCM) has been used to improve gastrointestinal dysfunction and to modify the immune response to inflammation for centuries. This study used six herbal plants and four TCM formulae to rate their efficacy in preventing S. Typhimurium infection via mouse model. Minimum bactericidal concentration (MBC) of Coptidis rhizome (CR) against the reference strain tallied 12.5 mg/ml and against clinical isolate ST21 was 25 mg/ml. MBCs of other herbal extracts and formulae on Salmonella Typhimurium strains were above 50 mg/ml. In the mice model, CR and Si Jun Zi Tang (SJZT) could significantly decrease the bacterial load in organs and blood after being challenged, along with body weight loss due to the infection. CR and SJZT alleviated infection induced interferon-gamma levels in the serum and tissues, and tumor necrosis factor-alpha (TNF-alpha) levels in intestinal tissues. CR and SJZT serum metabolites could suppress S. Typhimurium invasion and TNF-alpha expression in RAW264.7 cells. The therapeutic activity of CR and SJZT may involve berberine, ginsenoside Rb1, and glycyrrhizin, interfering with Salmonella when invading macrophages. CR and SJZT has shown potential in preventing S. Typhimurium infection through the regulation of the immune response. PMID- 25133543 TI - The global trade in fresh produce and the vagility of plant viruses: a case study in garlic. AB - As cuisine becomes globalized, large volumes of fresh produce are traded internationally. The potential exists for pathogens infecting fresh produce to hitchhike to new locations and perhaps to establish there. It is difficult to identify them using traditional methods if pathogens are novel, scarce, and/or unexpected. In an attempt to overcome this limitation, we used high-throughput sequencing technology as a means of detecting all RNA viruses infecting garlic (Allium sativum L.) bulbs imported into Australia from China, the USA, Mexico, Argentina and Spain, and those growing in Australia. Bulbs tested were grown over multiple vegetative generations and all were stably infected with one or more viruses, including two species not previously recorded in Australia. Present in various combinations from 10 garlic bulbs were 41 virus isolates representing potyviruses (Onion yellow dwarf virus, Leek yellow stripe virus), carlaviruses (Shallot latent virus, Garlic common latent virus) and allexiviruses (Garlic virus A, B, C, D, and X), for which 19 complete and 22 partial genome sequences were obtained, including the first complete genome sequences of two isolates of GarVD. The most genetically distinct isolates of GarVA and GarVX described so far were identified from Mexico and Argentina, and possible scenarios explaining this are presented. The complete genome sequence of an isolate of the potexvirus Asparagus virus 3 (AV3) was obtained in Australia from wild garlic (A. vineale L.), a naturalized weed. This is first time AV3 has been identified from wild garlic and the first time it has been identified beyond China and Japan. The need for routine generic diagnosis and appropriate legislation to address the risks to primary production and wild plant communities from pathogens spread through the international trade in fresh produce is discussed. PMID- 25133544 TI - Are articulatory settings mechanically advantageous for speech motor control? AB - We address the hypothesis that postures adopted during grammatical pauses in speech production are more "mechanically advantageous" than absolute rest positions for facilitating efficient postural motor control of vocal tract articulators. We quantify vocal tract posture corresponding to inter-speech pauses, absolute rest intervals as well as vowel and consonant intervals using automated analysis of video captured with real-time magnetic resonance imaging during production of read and spontaneous speech by 5 healthy speakers of American English. We then use locally-weighted linear regression to estimate the articulatory forward map from low-level articulator variables to high-level task/goal variables for these postures. We quantify the overall magnitude of the first derivative of the forward map as a measure of mechanical advantage. We find that postures assumed during grammatical pauses in speech as well as speech-ready postures are significantly more mechanically advantageous than postures assumed during absolute rest. Further, these postures represent empirical extremes of mechanical advantage, between which lie the postures assumed during various vowels and consonants. Relative mechanical advantage of different postures might be an important physical constraint influencing planning and control of speech production. PMID- 25133545 TI - Decontamination of adsorbed chemical warfare agents on activated carbon using hydrogen peroxide solutions. AB - Mild treatment with hydrogen peroxide solutions (3-30%) efficiently decomposes adsorbed chemical warfare agents (CWAs) on microporous activated carbons used in protective garments and air filters. Better than 95% decomposition of adsorbed sulfur mustard (HD), sarin, and VX was achieved at ambient temperatures within 1 24 h, depending on the H2O2 concentration. HD was oxidized to the nontoxic HD sulfoxide. The nerve agents were perhydrolyzed to the respective nontoxic methylphosphonic acids. The relative rapidity of the oxidation and perhydrolysis under these conditions is attributed to the microenvironment of the micropores. Apparently, the reactions are favored due to basic sites on the carbon surface. Our findings suggest a potential environmentally friendly route for decontamination of adsorbed CWAs, using H2O2 without the need of cosolvents or activators. PMID- 25133547 TI - Towards full citizenship: correlates of engagement with the gender identity law among transwomen in Argentina. AB - INTRODUCTION: In May 2012, Argentina passed its "Gender Identity" Law, which aimed to address the legal invisibility, discrimination and marginalization that transgender individuals have historically faced. The aim of this study was to explore factors associated with engagement with the Gender Identity Law among transwomen living in Argentina. METHODS: Data were derived from a 2013 nationwide, cross-sectional study involving transwomen in Argentina. Using multivariate logistic regression, we assessed the prevalence and factors associated with acquiring a gender-congruent identity card within the first 18 months of enactment of the Gender Identity Law. RESULTS: Among 452 transwomen, 260 (57.5%) reported that they had obtained a new gender-congruent identity card. In multivariate analysis, factors positively associated with acquiring a new ID were: previously experiencing discrimination by healthcare workers (adjusted odd ratio [aOR] = 2.01, 95% CI: 1.27-3.20); having engaged in transition procedures (aOR = 3.06, 95% CI: 1.58-5.93); and having a job other than sex work (aOR = 1.81, 95% CI: 1.06-3.10). Foreign born transwomen were less likely to have obtained a new ID (aOR = 0.14, 95% CI: 0.06-0.33). CONCLUSIONS: More than half of transwomen in our sample acquired a new gender-congruent ID within the first 18 months of enactment of the Gender Identity Law. However, access to and uptake of this right has been heterogeneous. In particular, our findings suggest that the most empowered transwomen may have been among the first to take advantage of this right. Although educational level, housing conditions, HIV status and sex work were not associated with the outcome, foreign-born status was a strong negative correlate of new ID acquisition. Therefore, additional efforts should be made in order to ensure that benefits of this founding policy reach all transwomen in Argentina. PMID- 25133548 TI - Determinants of patients' choice of provider in accessing brucellosis care among pastoral communities adjacent to lake Mburo National Park in Kiruhura District, Uganda. AB - BACKGROUND: Brucellosis is the commonest zoonotic infection worldwide with symptoms similar to other febrile syndromes such as malaria and typhoid fever. It is often easily misdiagnosed, resulting in underreporting and misdirected treatments. Understanding of the factors that influence brucellosis care seeking is essential in enhancing its effective management. Our study sought to determine the factors associated with choice of provider in accessing care for brucellosis among pastoral communities in Uganda. METHODS: This was a cross-sectional survey involving 245 randomly selected respondents previously diagnosed and treated for brucellosis, two months before the study. They were enrolled from three sub counties neighboring Lake Mburo National Park between December 2012 to April 2013. Data on socio-demographics, availability, accessibility, affordability and acceptability of health services were collected. A multivariable logistic regression model was fitted to determine association between independent and outcome variables using odds ratios and 95% confidence intervals with p value<=0.05 considered statistically significant. RESULTS: Of the 245 respondents, 127(51.8%) sought health care at government facilities and the rest at private. Respondents who were less likely to choose a government facility were either single (OR: 0.50, CI: 0.26-0.97), had general weakness (OR: 0.09, CI: 0.01 0.72) or whom family took a decision (OR: 0.52, CI: 0.28-0.97). At multivariable analysis, choice of government facility was influenced by primary education (aOR: 0.46, CI: 0.22-0.97), having six to ten household members (aOR:3.71, CI:1.84 7.49), family advice (aOR:0.64, CI: 0.23-0.91), distance >=10 kms (aOR:0.44, CI: 0.21-0.92), high costs at private clinics (aOR:0.01, CI:0.02-0.15) and no diagnosis at government facility (aOR:0.11, CI:0.01-0.97). Females were more likely to seek health care at government facilities, while those with tertiary education were less likely, after the first provider. CONCLUSIONS: Females and households with six to ten members were more likely to choose government facilities. Government facilities need to be equipped to attract more patients. PMID- 25133546 TI - Evaluation of uric acid as a prognostic blood-based marker in a large cohort of pancreatic cancer patients. AB - BACKGROUND: Recently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC. PATIENTS AND METHODS: Data from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated. RESULTS: None of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus >=5.1 mg/dl, p = 0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR = 1.373%; CI = 1.077-1.751; p = 0.011). CONCLUSION: In conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management. PMID- 25133549 TI - Cross-checking different sources of mobility information. AB - The pervasive use of new mobile devices has allowed a better characterization in space and time of human concentrations and mobility in general. Besides its theoretical interest, describing mobility is of great importance for a number of practical applications ranging from the forecast of disease spreading to the design of new spaces in urban environments. While classical data sources, such as surveys or census, have a limited level of geographical resolution (e.g., districts, municipalities, counties are typically used) or are restricted to generic workdays or weekends, the data coming from mobile devices can be precisely located both in time and space. Most previous works have used a single data source to study human mobility patterns. Here we perform instead a cross check analysis by comparing results obtained with data collected from three different sources: Twitter, census, and cell phones. The analysis is focused on the urban areas of Barcelona and Madrid, for which data of the three types is available. We assess the correlation between the datasets on different aspects: the spatial distribution of people concentration, the temporal evolution of people density, and the mobility patterns of individuals. Our results show that the three data sources are providing comparable information. Even though the representativeness of Twitter geolocated data is lower than that of mobile phone and census data, the correlations between the population density profiles and mobility patterns detected by the three datasets are close to one in a grid with cells of 2*2 and 1*1 square kilometers. This level of correlation supports the feasibility of interchanging the three data sources at the spatio-temporal scales considered. PMID- 25133551 TI - Topical prescription contrition. PMID- 25133552 TI - Monodisperse colloidal gallium nanoparticles: synthesis, low temperature crystallization, surface plasmon resonance and Li-ion storage. AB - We report a facile colloidal synthesis of gallium (Ga) nanoparticles with the mean size tunable in the range of 12-46 nm and with excellent size distribution as small as 7-8%. When stored under ambient conditions, Ga nanoparticles remain stable for months due to the formation of native and passivating Ga-oxide layer (2-3 nm). The mechanism of Ga nanoparticles formation is elucidated using nuclear magnetic resonance spectroscopy and with molecular dynamics simulations. Size dependent crystallization and melting of Ga nanoparticles in the temperature range of 98-298 K are studied with X-ray powder diffraction, specific heat measurements, transmission electron microscopy, and X-ray absorption spectroscopy. The results point to delta (delta)-Ga polymorph as a single low temperature phase, while phase transition is characterized by the large hysteresis and by the large undercooling of crystallization and melting points down to 140-145 and 240-250 K, respectively. We have observed size-tunable plasmon resonance in the ultraviolet and visible spectral regions. We also report stable operation of Ga nanoparticles as anode material for Li-ion batteries with storage capacities of 600 mAh g(-1), 50% higher than those achieved for bulk Ga under identical testing conditions. PMID- 25133553 TI - Mimosa (Mimosa caesalpiniifolia) prevents oxidative DNA damage induced by cadmium exposure in Wistar rats. AB - The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is used in the traditional medicine systems for treating bacterial, fungal, parasitic and inflammatory conditions. The aim of this study was to evaluate the antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia) in multiple rodent organs subjected to intoxication with cadmium chloride. A total of 40 Wistar rats (8 weeks old, 250 g) were distributed into eight groups (n = 5), as follows: Control group (non-treated group, CTRL); Cadmium exposed group (Cd); cadmium exposure and treated with extract at 62.5 mg/kg/day; cadmium exposure and treated with extract at 125 mg/kg/day; cadmium exposure and treated with extract at 250 mg/kg/day; cadmium exposure and treated with ethyl acetate fraction at 62.5 mg/kg/day. For evaluating the toxicogenetic potential of mimosa, two groups were included in the study being treated with extract at 250 mg/kg/day and acetate fraction of mimosa at 62 mg/kg/day, only. Extract of mimosa at concentrations of 62.5 and 125 mg decreased DNA damage in animals intoxicated with cadmium when compared to cadmium group. In a similar manner, treatment with ethyl acetate fraction of mimosa at 62.5 mg concentration in animals previously exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar manner, the treatment with ethyl acetate fraction reduced DNA damage in liver cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated with 125 mg of extract as well as those intoxicated to cadmium and treated with 62.5 of acetate fraction of mimosa. Taken together, our results indicate that mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral blood cells of rats as a result of antioxidant activity. PMID- 25133554 TI - May maternal anti-mullerian hormone levels predict adverse maternal and perinatal outcomes in preeclampsia? AB - BACKGROUND: Prediction of preeclampsia and adverse maternal and perinatal outcomes with biomarkers has been proposed previously. Anti-mullerian hormone (AMH) is a growth factor, which is primarily responsible of the regression of the mullerian duct, but also used to predict ovarian reserve and decreases with age similar to the fertility. AIM: To evaluate the predictive role of maternal anti mullerian hormone (mAMH) in adverse maternal and perinatal outcomes in preeclampsia. METHODS: This prospective case-control study was conducted at current high-risk pregnancy department in a tertiary research hospital and 45 cases with preeclampsia classified as study group and 42 as control group. Data collected and evaluated were; age, body mass index (BMI), marriage duration (MD), gestational weeks (GW), gravidity, parity, mode of delivery, birth weight, newborn Apgar score, newborn gender, maternal complication, perinatal outcome, some laboratory parameters and mAMH. The association between mAMH levels and maternal and fetal outcomes were evaluated. RESULTS: There were no statistically significant differences between groups in terms of age, BMI, MD, gravidity, parity and newborn gender (p > 0.05). GW, vaginal delivery, birth weight, newborn Apgar score, were statistically significantly lower in preeclamptic patients when compared with non-preeclamptic patients (p < 0.001). Adverse maternal and perinatal outcomes were statistically significantly higher in the study group (p < 0.001). The laboratory values [alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), creatinine, lactic dehydrogenase (LDH), uric acid and fibrinogen) were statistically significantly lower in the control group (p < 0.001). The mAMH level was significantly lower in the preeclamptic group (p: 0.035). There was no correlation between mAMH levels and demographic and clinical parameters. The area under the ROC curve (AUC) was 0.590 and the cut-off value was 0.365 ng/ml with sensitivity of 67.4% and specificity of 47.1% for mAMH. Logistic regression analysis showed a statistically insignificance between mAMH and maternal complication and perinatal outcome (p: 0.149). CONCLUSION: According to this study, mAMH level was lower in preeclamptic patients than in normal pregnants, and is found to be a discriminative factor with low sensitivity and specificity. There was no relationship between mAMH and adverse maternal and perinatal outcomes. Further randomized controlled studies with more participants are needed to evaluate the accurate effects of mAMH levels on preeclampsia and should increase the power of mAMH levels in predicting the preeclampsia. PMID- 25133555 TI - [Interesting cases in IOL implantation]. PMID- 25133556 TI - [Recurrent anterior chamber and vitreous bleeding after cataract surgery]. PMID- 25133550 TI - Tandem RNA chimeras contribute to transcriptome diversity in human population and are associated with intronic genetic variants. AB - Chimeric RNAs originating from two or more different genes are known to exist not only in cancer, but also in normal tissues, where they can play a role in human evolution. However, the exact mechanism of their formation is unknown. Here, we use RNA sequencing data from 462 healthy individuals representing 5 human populations to systematically identify and in depth characterize 81 RNA tandem chimeric transcripts, 13 of which are novel. We observe that 6 out of these 81 chimeras have been regarded as cancer-specific. Moreover, we show that a prevalence of long introns at the fusion breakpoint is associated with the chimeric transcripts formation. We also find that tandem RNA chimeras have lower abundances as compared to their partner genes. Finally, by combining our results with genomic data from the same individuals we uncover intronic genetic variants associated with the chimeric RNA formation. Taken together our findings provide an important insight into the chimeric transcripts formation and open new avenues of research into the role of intronic genetic variants in post-transcriptional processing events. PMID- 25133557 TI - [Refractive lens exchange with a multifocal lens: well operated, but still dissatisfied]. PMID- 25133558 TI - [Phakic intraocular lens implantation in the case of a large white-to-white distance]. PMID- 25133559 TI - [Alterations of intraocular pressure in comparison of self- and external administered topical antiglaucomatosa during diurnal intraocular pressure measurements]. AB - BACKGROUND: The correct self-administration of topical antiglaucomatous eye drops is important for the success of glaucoma treatment. Individual impairment, like increased age, decreased visual acuity, impaired visual-field perception or the frequency of drug appliance may influence a correct application technique and the patients compliance and therewith intraocular pressure (IOP). The aim of this study was to explore alterations of IOP due to self versus external administration (by trained medical personnel) of topical antiglaucomatous eye drops due to impairing factors. MATERIAL AND METHODS: A prospective analysis was undertaken of 123 patients with primary chronic open-angle glaucoma receiving a diurnal intraocular pressure (DIP) measurement over 72 hours at our department. During the first 24 hours, the application of topical eye drops was self administered by patients (SA), while the application of eye drops within the following 48 hours was performed by trained medical personnel (EA). Alterations of mean intraocular pressure (MIP) and diurnal fluctuations (DF) between EA and SA were analysed with regard to initial IOP, restrictions of visual field perception, visual acuity, age, general health status and frequency of daily eye drop administration. RESULTS: Overall comparable MIP in SA and EA was seen. 19.2 43.9 % of the patients with an initial IOP >= 11 mmHg showed beneficial effects of EA with lowering of IOP under 15.5 mmHg. 27.6 % of the patients showed lowering of DF < 5 mmHg due to EA. EA influenced DF beneficially in cases of poor visual acuity (<= 0.1, - 0.8 mmHg) and frequent drop administration (- 0.75 mmHg). CONCLUSIONS: Subpopulations of investigated patients showed lowering of MIP due to EA, although EA showed no MIP lowering effects in comparison with SA in general. Glaucoma-impaired patients show decreased DF by EA. Particularly beneficial influences to DF by EA were observed due to impaired visual acuity and frequent drop administration. We recommend a 72-hour DIP to evaluate individual parameters influencing the success of topical glaucomatous treatment. The benefit of EA in patients with certain impairments should be the subject of further investigations. PMID- 25133561 TI - [Treatment of primary open angle glaucoma in a case of multiple chemical sensitivity syndrome: a case report]. PMID- 25133560 TI - [The relationship between the temperature increase caused by phacoemulsification and the damage to the corneal endothelium]. AB - PURPOSE: Endothelial cell damage can be found after a phacoemulsification. The reason for this cell damage is not yet known. The temperature rise inside the anterior chamber during the emulsification of the lens is considered as a potential damage mechanism. The aim of this study was to investigate the relationship between the temperature increase and the cell damage. MATERIALS AND METHODS: This study was performed with 86 enucleated porcine eyes, which were divided into six groups A-F. Group A served as control group. Phacoemulsification was simulated in the groups B-E with different surgically relevant system settings. The temperature change was measured simultaneously with temperature sensors inside the anterior chamber. Inside the eyes of group F, the instruments were positioned and irrigation and aspiration were activated, but no ultrasound was applied. For all 86 corneas, the endothelial cell damage was quantified with a standardised evaluation protocol using scanning electron microscopy (SEM). A potential correlation was checked between the observed cell damage and the measured temperature rise. RESULTS: The highest temperature increase in group E with an obstructed aspiration line and an output power setting of 50 % was 17.77 degrees C. The temperature increase in group D with an output power setting of 100 % and unblocked fluid flow was significantly lower (p = 0.006). The highest temperature increase in group D was 8.89 degrees C. In contrast, the cells in group D were rated with a significantly lower score value than the cells in group E (p < 0.001). No significant correlation between the temperature rise and the cell damage could be obtained in due consideration of all measured data. However, an increase of the output power setting was connected with a non-linear increase of the cell loss. CONCLUSION: The temperature rise was not the main reason for the endothelial cell damage in the performed experiments. Therefore, there seems to be no causal relationship between the temperature increase inside the anterior chamber during a common phacoemulsification and the endothelial cell damage. Due to the strong dependence between the output power setting and the cell damage, the lowest output power setting should be used during surgery which ensures the emulsification of the nucleus. PMID- 25133562 TI - [Objective refraction - retinoscopy]. PMID- 25133564 TI - The rationale for use of Ulipristal Acetate as first line in emergency contraception: biological and clinical evidence. AB - Ulipristal acetate (UPA) was licensed as an emergency contraceptive (EC) in Europe in 2009. By the end of May 2013, over 1.4 million courses had been used. The rationale for using UPA for EC in favor of the much more commonly used levonorgestrel (LNG) is based on data on efficacy, safety and side effects. EFFICACY: In two large clinical trials among women presenting for EC up to 120 hours after unprotected sex, UPA was as effective as LNG at preventing pregnancy. When the two trials were combined in a meta analysis UPA was superior, almost halving the risk of pregnancy compared with LNG. Biomedical studies have shown that UPA inhibits or delays ovulation more effectively than LNG at a stage of the cycle when the risk of pregnancy is highest. Safety and side effects: UPA and LNG have similar side effect profiles and to date no serious adverse events have been attributed to use of UPA for EC. Data on pregnancies conceived in association with UPA use are reassuring. There is no evidence for teratogenesis or for any increased risk of ectopic pregnancy or miscarriage. AVAILABILITY: Use of UPA will remain limited until it is available without a doctor's prescription. PMID- 25133565 TI - Using skype to conduct interviews for psychosocial research. PMID- 25133566 TI - Developing guidelines for mentorship. PMID- 25133573 TI - Correlation of [RuCl3(dppb)(VPy)] cytotoxicity with its effects on the cell membranes: an investigation using Langmuir monolayers as membrane models. AB - One of the major challenges in drug design is to identify compounds with potential toxicity toward target cells, preferably with molecular-level understanding of their mode of action. In this study, the antitumor property of a ruthenium complex, mer-[RuCl3(dppb)(VPy)] (dppb = 1,4 bis(diphenylphosphine)butane and VPy = 4-vinylpyridine) (RuVPy), was analyzed. Results showed that this compound led to a mortality rate of 50% of HEp-2 cell with 120 +/- 10 MUmol L(-1), indicating its high toxicity. Then, to prove if its mode of action is associated with its interaction with cell membranes, Langmuir monolayers were used as a membrane model. RuVPy had a strong effect on the surface pressure isotherms, especially on the elastic properties of both the zwitterionic dipalmitoylphosphatidylcholine (DPPC) and the negatively charged dipalmitoylphosphatidylglycerol (DPPG) phospholipids. These data were confirmed by polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). In addition, interactions between the positive group from RuVPy and the phosphate group from the phospholipids were corroborated by density functional theory (DFT) calculations, allowing the determination of the Ru complex orientation at the air water interface. Although possible contributions from receptors or other cell components cannot be discarded, the results reported here represent evidence for significant effects on the cell membranes which are probably associated with the high toxicity of RuVPy. PMID- 25133574 TI - A possible link between food and mood: dietary impact on gut microbiota and behavior in BALB/c mice. AB - Major depressive disorder is a debilitating disease in the Western World. A western diet high in saturated fat and refined sugar seems to play an important part in disease development. Therefore, this study is aimed at investigating whether saturated fat or sucrose predisposes mice to develop behavioral symptoms which can be interpreted as depression-like, and the possible influence of the gut microbiota (GM) in this. Fourty-two mice were randomly assigned to one of three experimental diets, a high-fat, a high-sucrose or a control diet for thirteen weeks. Mice on high-fat diet gained more weight (p = 0.00009), displayed significantly less burrowing behavior than the control mice (p = 0.034), and showed decreased memory in the Morris water maze test compared to mice on high sucrose diet (p = 0.031). Mice on high-sucrose diet burrowed less goal-oriented, showed greater latency to first bout of immobility in the forced swim test when compared to control mice (p = 0.039) and high-fat fed mice (p = 0.013), and displayed less anxiety than mice on high-fat diet in the triple test (p = 0.009). Behavioral changes were accompanied by a significant change in GM composition of mice fed a high-fat diet, while no difference between diet groups was observed for sucrose preferences, LPS, cholesterol, HbA1c, BDNF and the cytokines IL 1alpha, IL-1beta, IL-6, IL-10, IL-12(p70), IL-17 and TNF-alpha. A series of correlations was found between GM, behavior, BDNF and inflammatory mediators. In conclusion, the study shows that dietary fat and sucrose affect behavior, sometimes in opposite directions, and suggests a possible association between GM and behavior. PMID- 25133575 TI - Cloning and characterization of a Phragmites australis phytochelatin synthase (PaPCS) and achieving Cd tolerance in tall fescue. AB - The production of phytochelatins (PCs) provides an important means for plants to achieve tolerance to cadmium (Cd) toxicity. A reed gene encoding PC synthase (PaPCS) was isolated and its function tested through its heterologous expression in a strain of yeast sensitive to Cd. Subsequently, the Cd sensitive and high biomass accumulating species tall fescue was transformed either with PaPCS or PaGCS (a glutamyl cysteine synthetase gene of reed) on their own (single transformants), or with both genes together in the same transgene cassette (double transformant). The single and double transformants showed greater Cd tolerance and accumulated more Cd and PC than wild type plants, and their Cd leaf/root ratio content was higher. The ranking in terms of Cd and PC content for the various transgenic lines was double transformants>PaGCS single transformants>PaPCS single transformants>wild type. Thus PaGCS appears to exert a greater influence than PaPCS over PC synthesis and Cd tolerance/accumulation. The double transformant has interesting potential for phytoremediation. PMID- 25133576 TI - The burden of influenza and RSV among inpatients and outpatients in rural western Kenya, 2009-2012. AB - BACKGROUND: In Kenya, detailed data on the age-specific burden of influenza and RSV are essential to inform use of limited vaccination and treatment resources. METHODS: We analyzed surveillance data from August 2009 to July 2012 for hospitalized severe acute respiratory illness (SARI) and outpatient influenza like illness (ILI) at two health facilities in western Kenya to estimate the burden of influenza and respiratory syncytial virus (RSV). Incidence rates were estimated by dividing the number of cases with laboratory-confirmed virus infections by the mid-year population. Rates were adjusted for healthcare-seeking behavior, and to account for patients who met the SARI/ILI case definitions but were not tested. RESULTS: The average annual incidence of influenza-associated SARI hospitalization per 1,000 persons was 2.7 (95% CI 1.8-3.9) among children <5 years and 0.3 (95% CI 0.2-0.4) among persons >=5 years; for RSV-associated SARI hospitalization, it was 5.2 (95% CI 4.0-6.8) among children <5 years and 0.1 (95% CI 0.0-0.2) among persons >=5 years. The incidence of influenza-associated medically-attended ILI per 1,000 was 24.0 (95% CI 16.6-34.7) among children <5 years and 3.8 (95% CI 2.6-5.7) among persons >=5 years. The incidence of RSV associated medically-attended ILI was 24.6 (95% CI 17.0-35.4) among children <5 years and 0.8 (95% CI 0.3-1.9) among persons >=5 years. CONCLUSIONS: Influenza and RSV both exact an important burden in children. This highlights the possible value of influenza vaccines, and future RSV vaccines, for Kenyan children. PMID- 25133577 TI - Voxel-based MRI intensitometry reveals extent of cerebral white matter pathology in amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons. Advanced MRI techniques such as diffusion tensor imaging have shown great potential in capturing a common white matter pathology. However the sensitivity is variable and diffusion tensor imaging is not yet applicable to the routine clinical environment. Voxel-based morphometry (VBM) has revealed grey matter changes in ALS, but the bias-reducing algorithms inherent to traditional VBM are not optimized for the assessment of the white matter changes. We have developed a novel approach to white matter analysis, namely voxel-based intensitometry (VBI). High resolution T1-weighted MRI was acquired at 1.5 Tesla in 30 ALS patients and 37 age-matched healthy controls. VBI analysis at the group level revealed widespread white matter intensity increases in the corticospinal tracts, corpus callosum, sub-central, frontal and occipital white matter tracts and cerebellum. VBI results correlated with disease severity (ALSFRS-R) and patterns of cerebral involvement differed between bulbar- and limb-onset. VBI would be easily translatable to the routine clinical environment, and once optimized for individual analysis offers significant biomarker potential in ALS. PMID- 25133578 TI - Stable, covalent attachment of laminin to microposts improves the contractility of mouse neonatal cardiomyocytes. AB - The mechanical output of contracting cardiomyocytes, the muscle cells of the heart, relates to healthy and disease states of the heart. Culturing cardiomyocytes on arrays of elastomeric microposts can enable inexpensive and high-throughput studies of heart disease at the single-cell level. However, cardiomyocytes weakly adhere to these microposts, which limits the possibility of using biomechanical assays of single cardiomyocytes to study heart disease. We hypothesized that a stable covalent attachment of laminin to the surface of microposts improves cardiomyocyte contractility. We cultured cells on polydimethylsiloxane microposts with laminin covalently bonded with the organosilanes 3-glycidoxypropyltrimethoxysilane and 3-aminopropyltriethoxysilane with glutaraldehyde. We measured displacement of microposts induced by the contractility of mouse neonatal cardiomyocytes, which attach better than mature cardiomyocytes to substrates. We observed time-dependent changes in contractile parameters such as micropost deformation, contractility rates, contraction and relaxation speeds, and the times of contractions. These parameters were affected by the density of laminin on microposts and by the stability of laminin binding to micropost surfaces. Organosilane-mediated binding resulted in higher laminin surface density and laminin binding stability. 3-glycidoxypropyltrimethoxysilane provided the highest laminin density but did not provide stable protein binding with time. Higher surface protein binding stability and strength were observed with 3-aminopropyltriethoxysilane with glutaraldehyde. In cultured cardiomyocytes, contractility rate, contraction speeds, and contraction time increased with higher laminin stability. Given these variations in contractile function, we conclude that binding of laminin to microposts via 3 aminopropyltriethoxysilane with glutaraldehyde improves contractility observed by an increase in beating rate and contraction speed as it occurs during the postnatal maturation of cardiomyocytes. This approach is promising for future studies to mimic in vivo tissue environments. PMID- 25133579 TI - Visualization of mouse neuronal ganglia infected by Herpes Simplex Virus 1 (HSV 1) using multimodal non-linear optical microscopy. AB - Herpes simplex virus 1 (HSV-1) is a neurotropic virus that causes skin lesions and goes on to enter a latent state in neurons of the trigeminal ganglia. Following stress, the virus may reactivate from latency leading to recurrent lesions. The in situ study of neuronal infections by HSV-1 is critical to understanding the mechanisms involved in the biology of this virus and how it causes disease; however, this normally requires fixation and sectioning of the target tissues followed by treatment with contrast agents to visualize key structures, which can lead to artifacts. To further our ability to study HSV-1 neuropathogenesis, we have generated a recombinant virus expressing a second generation red fluorescent protein (mCherry), which behaves like the parental virus in vivo. By optimizing the application of a multimodal non-linear optical microscopy platform, we have successfully visualized in unsectioned trigeminal ganglia of mice both infected cells by two-photon fluorescence microscopy, and myelinated axons of uninfected surrounding cells by coherent anti-Stokes Raman scattering (CARS) microscopy. These results represent the first report of CARS microscopy being combined with 2-photon fluorescence microscopy to visualize virus-infected cells deep within unsectioned explanted tissue, and demonstrate the application of multimodal non-linear optical microscopy for high spatial resolution biological imaging of tissues without the use of stains or fixatives. PMID- 25133580 TI - Expression of wheat high molecular weight glutenin subunit 1Bx is affected by large insertions and deletions located in the upstream flanking sequences. AB - To better understand the transcriptional regulation of high molecular weight glutenin subunit (HMW-GS) expression, we isolated four Glu-1Bx promoters from six wheat cultivars exhibiting diverse protein expression levels. The activities of the diverse Glu-1Bx promoters were tested and compared with beta-glucuronidase (GUS) reporter fusions. Although all the full-length Glu-1Bx promoters showed endosperm-specific activities, the strongest GUS activity was observed with the 1Bx7OE promoter in both transient expression assays and stable transgenic rice lines. A 43 bp insertion in the 1Bx7OE promoter, which is absent in the 1Bx7 promoter, led to enhanced expression. Analysis of promoter deletion constructs confirmed that a 185 bp MITE (miniature inverted-repeat transposable element) in the 1Bx14 promoter had a weak positive effect on Glu-1Bx expression, and a 54 bp deletion in the 1Bx13 promoter reduced endosperm-specific activity. To investigate the effect of the 43 bp insertion in the 1Bx7OE promoter, a functional marker was developed to screen 505 Chinese varieties and 160 European varieties, and only 1Bx7-type varieties harboring the 43 bp insertion in their promoters showed similar overexpression patterns. Hence, the 1Bx7OE promoter should be important tool in crop genetic engineering as well as in molecular assisted breeding. PMID- 25133582 TI - Gemini surfactants affect the structure, stability, and activity of ribonuclease Sa. AB - Gemini surfactants have important advantages, e.g., low micromolar CMCs and slow millisecond monomer <-> micelle kinetics, for membrane mimetics and for delivering nucleic acids for gene therapy or RNA silencing. However, as a prerequisite, it is important to characterize interactions occurring between Gemini surfactants and proteins. Here NMR and CD spectroscopies are employed to investigate the interactions of cationic Gemini surfactants with RNase Sa, a negatively charged ribonuclease. We find that RNase Sa binds Gemini surfactant monomers and micelles at pH values above 4 to form aggregates. Below pH 4, where the protein is positively charged, these aggregates dissolve and interactions are undetectable. Thermal denaturation experiments show that surfactant lowers RNase Sa's conformational stability, suggesting that surfactant binds the protein's denatured state preferentially. Finally, Gemini surfactants were found to bind RNA, leading to the formation of large complexes. Interestingly, Gemini surfactant binding did not prevent RNase Sa from cleaving RNA. PMID- 25133581 TI - Next-generation sequencing of colorectal cancers in chinese: identification of a recurrent frame-shift and gain-of-function Indel mutation in the TFDP1 gene. AB - Abstract Re-sequencing of target genes is a highly effective approach for identifying mutations in cancers. Mutations, including indels (insertions, deletions, and the combination of the two), play important roles in carcinogenesis. Combining genomic DNA capture using high-density oligonucleotide microarrays (NimbleGen, Inc.) with next-generation high-throughput sequencing, we identified approximately 1600 indels for colorectal cancers in the Chinese population. Among them, 5 indels were localized to exonic regions of genes, including the TFDP1 (transcription factor Dp-1) gene. TFDP1 is an important transcription factor that coordinates with E2F proteins, thereby promoting transcription of E2F target genes and regulating the cell cycle and differentiation. We report here the identification of a recurrent frame-shift indel mutation (named indel84) in the TFDP1 gene in colorectal cancers by next generation sequencing. We found in a validation set that TFDP1 indel84 is present in 70% of colorectal cancer (CRC) tissues. Wild-type TFDP1 encodes a protein of 410 amino acids with a potential DNA binding site at its N-terminal followed by several functional protein domains. The TFDP1 indel cDNA would generate an alternative TFDP1 protein missing the first 120 amino acids and potentially affecting the DNA binding domain. We further demonstrated that the TFDP1 indel84 mutation generated a gain-of-function phenotype by increasing cell proliferation, migration, and invasion of CRC cells. Our study identified a key molecular event for CRC that might have great diagnostic and therapeutic potentials. PMID- 25133583 TI - TRPC1 contributes to the Ca2+-dependent regulation of adenylate cyclases. AB - SOCE (store-operated Ca2+ entry) is mediated via specific plasma membrane channels in response to ER (endoplasmic reticulum) Ca2+ store depletion. This route of Ca2+ entry is central to the dynamic interplay between Ca2+ and cAMP signalling in regulating the activity of Ca2+-sensitive adenylate cyclase isoforms (AC1, AC5, AC6 and AC8). Two proteins have been identified as key components of SOCE: STIM1 (stromal interaction molecule 1), which senses ER Ca2+ store content and translocates to the plasma membrane upon store depletion, where it then activates Orai1, the pore-forming component of the CRAC (Ca2+ release activated Ca2+) channel. Previous studies reported that co-expression of STIM1 and Orai1 in HEK-293 (human embryonic kidney 293) cells enhances Ca2+-stimulated AC8 activity and that AC8 and Orai1 directly interact to enhance this regulation. Nonetheless, the additional involvement of TRPC (transient receptor potential canonical) channels in SOCE has also been proposed. In the present study, we evaluate the contribution of TRPC1 to SOCE-mediated regulation of Ca2+-sensitive ACs in HEK-293 cells stably expressing AC8 (HEK-AC8) and HSG (human submandibular gland) cells expressing an endogenous Ca2+-inhibited AC6. We demonstrate a role for TRPC1 as an integral component of SOCE, alongside STIM1 and Orai1, in regulating Ca2+ fluxes within AC microdomains and influencing cAMP production. PMID- 25133585 TI - Eukaryotic expression system Pichia pastoris affects the lipase catalytic properties: a monolayer study. AB - Recombinant DNA methods are being widely used to express proteins in both prokaryotic and eukaryotic cells for both fundamental and applied research purposes. Expressed protein must be well characterized to be sure that it retains the same properties as the native one, especially when expressed protein will be used in the pharmaceutical field. In this aim, interfacial and kinetic properties of native, untagged recombinant and tagged recombinant forms of a pancreatic lipase were compared using the monomolecular film technique. Turkey pancreatic lipase (TPL) was chosen as model. A kinetic study on the dependence of the stereoselectivity of these three forms on the surface pressure was performed using three dicaprin isomers spread in the form of monomolecular films at the air water interface. The heterologous expression and the N-His-tag extension were found to modify the pressure preference and decrease the catalytic hydrolysis rate of three dicaprin isomers. Besides, the heterologous expression was found to change the TPL regioselectivity without affecting its stereospecificity contrary to the N-tag extension which retained that regioselectivity and changed the stereospecificity at high surface pressures. The study of parameters, termed Recombinant expression Effects on Catalysis (REC), N-Tag Effects on Catalysis (TEC), and N-Tag and Recombinant expression Effects on Catalysis (TREC) showed that the heterologous expression effects on the catalytic properties of the TPL were more deleterious than the presence of an N-terminal tag extension. PMID- 25133586 TI - Photodissociation of pyrene cations: structure and energetics from C16H10(+) to C14(+) and almost everything in between. AB - The unimolecular dissociation of the pyrene radical cation, C16H10(+*), has been explored using a combination of computational techniques and experimental approaches, such as multiple photon absorption in the cold ion trap Piege a Ions pour la Recherche et l'Etude de Nouvelles Especes Astrochimiques (PIRENEA) and imaging photoelectron photoion coincidence spectrometry (iPEPICO). In total, 22 reactions, involving the fragmentation cascade (H, C2H2, and C4H2 loss) from the pyrene radical cation down to the C14(+*) fragment ion, have been studied using PIRENEA. Branching ratios have been measured for reactions from C16H10(+*), C16H8(+*), and C16H5(+). Density functional theory calculations of the fragmentation pathways observed experimentally and postulated theoretically lead to 17 unique structures. One important prediction is the opening of the pyrene ring system starting from the C16H4(+*) radical. In the iPEPICO experiments, only two reactions could be studied, namely, R1 C16H10(+*) -> C16H9(+) + H (m/z = 201) and R2 C16H9(+) -> C16H8(+*) + H (m/z = 200). The activation energies for these reactions were determined to be 5.4 +/- 1.2 and 3.3 +/- 1.1 eV, respectively. PMID- 25133584 TI - Physiological and genomic features of a novel sulfur-oxidizing gammaproteobacterium belonging to a previously uncultivated symbiotic lineage isolated from a hydrothermal vent. AB - Strain Hiromi 1, a sulfur-oxidizing gammaproteobacterium was isolated from a hydrothermal vent chimney in the Okinawa Trough and represents a novel genus that may include a phylogenetic group found as endosymbionts of deep-sea gastropods. The SSU rRNA gene sequence similarity between strain Hiromi 1 and the gastropod endosymbionts was approximately 97%. The strain was shown to grow both chemolithoautotrophically and chemolithoheterotrophically with an energy metabolism of sulfur oxidation and O2 or nitrate reduction. Under chemolithoheterotrophic growth conditions, the strain utilized organic acids and proteinaceous compounds as the carbon and/or nitrogen sources but not the energy source. Various sugars did not support growth as a sole carbon source. The observation of chemolithoheterotrophy in this strain is in line with metagenomic analyses of endosymbionts suggesting the occurrence of chemolithoheterotrophy in gammaproteobacterial symbionts. Chemolithoheterotrophy and the presence of homologous genes for virulence- and quorum sensing-related functions suggest that the sulfur-oxidizing chomolithotrophic microbes seek animal bodies and microbial biofilm formation to obtain supplemental organic carbons in hydrothermal ecosystems. PMID- 25133587 TI - Diastereoselective N-sulfonylaminoalkenylation of azulenes from terminal alkynes and azides via N-sulfonyl-1,2,3-triazoles. AB - The development of rhodium-catalyzed diastereoselective N sulfonylaminoalkenylation of azulenes using N-sulfonyltriazoles is described. This procedure can be successfully applied to rhodium-catalyzed diastereoselective N-sulfonylaminoalkenylation of azulenes starting from terminal alkynes and N-sulfonylazides via a three-component semi-one-pot process. PMID- 25133588 TI - Reproducibility and consistency of proteomic experiments on natural populations of a non-model aquatic insect. AB - Population proteomics has a great potential to address evolutionary and ecological questions, but its use in wild populations of non-model organisms is hampered by uncontrolled sources of variation. Here we compare the response to temperature extremes of two geographically distant populations of a diving beetle species (Agabus ramblae) using 2-D DIGE. After one week of acclimation in the laboratory under standard conditions, a third of the specimens of each population were placed at either 4 or 27 degrees C for 12 h, with another third left as a control. We then compared the protein expression level of three replicated samples of 2-3 specimens for each treatment. Within each population, variation between replicated samples of the same treatment was always lower than variation between treatments, except for some control samples that retained a wider range of expression levels. The two populations had a similar response, without significant differences in the number of protein spots over- or under-expressed in the pairwise comparisons between treatments. We identified exemplary proteins among those differently expressed between treatments, which proved to be proteins known to be related to thermal response or stress. Overall, our results indicate that specimens collected in the wild are suitable for proteomic analyses, as the additional sources of variation were not enough to mask the consistency and reproducibility of the response to the temperature treatments. PMID- 25133589 TI - Exploring the mechanisms of differentiation, dedifferentiation, reprogramming and transdifferentiation. AB - We explored the underlying mechanisms of differentiation, dedifferentiation, reprogramming and transdifferentiation (cell type switchings) from landscape and flux perspectives. Lineage reprogramming is a new regenerative method to convert a matured cell into another cell including direct transdifferentiation without undergoing a pluripotent cell state and indirect transdifferentiation with an initial dedifferentiation-reversion (reprogramming) to a pluripotent cell state. Each cell type is quantified by a distinct valley on the potential landscape with higher probability. We investigated three driving forces for cell fate decision making: stochastic fluctuations, gene regulation and induction, which can lead to cell type switchings. We showed that under the driving forces the direct transdifferentiation process proceeds from a differentiated cell valley to another differentiated cell valley through either a distinct stable intermediate state or a certain series of unstable indeterminate states. The dedifferentiation process proceeds through a pluripotent cell state. Barrier height and the corresponding escape time from the valley on the landscape can be used to quantify the stability and efficiency of cell type switchings. We also uncovered the mechanisms of the underlying processes by quantifying the dominant biological paths of cell type switchings on the potential landscape. The dynamics of cell type switchings are determined by both landscape gradient and flux. The flux can lead to the deviations of the dominant biological paths for cell type switchings from the naively expected landscape gradient path. As a result, the corresponding dominant paths of cell type switchings are irreversible. We also classified the mechanisms of cell fate development from our landscape theory: super-critical pitchfork bifurcation, sub-critical pitchfork bifurcation, sub-critical pitchfork with two saddle-node bifurcation, and saddle-node bifurcation. Our model showed good agreements with the experiments. It provides a general framework to explore the mechanisms of differentiation, dedifferentiation, reprogramming and transdifferentiation. PMID- 25133591 TI - Potential of cycloaddition reactions to generate cytotoxic metal drugs in vitro. AB - Severe general toxicity issues blight many chemotherapeutics utilized in the treatment of cancers, resulting in the need for more selective drugs able to exert their biological activity at only the required location(s). Toward this aim, we report the development of an organometallic ruthenium compound, functionalized through a eta(6)-bound arene ligand with a bicyclononyne derivative, able to participate in strain-promoted cycloaddition reactions with tetrazines. We show that combination of the ruthenium compound with a ditetrazine in biological media results in the in situ formation of a dinuclear molecule that is more cytotoxic toward cancer cells than the starting mononuclear ruthenium compound and tetrazine components. Such an approach may be extended to in vivo applications to construct a cytotoxic metallodrug at a tumor site, providing a novel approach toward the turn-on cytotoxicity of metallodrugs in the treatment of cancer. PMID- 25133590 TI - Lactobacillus casei reduces susceptibility to type 2 diabetes via microbiota mediated body chloride ion influx. AB - Gut microbiota mediated low-grade inflammation is involved in the onset of type 2 diabetes (T2DM). In this study, we used a high fat sucrose (HFS) diet-induced pre insulin resistance and a low dose-STZ HFS rat models to study the effect and mechanism of Lactobacillus casei Zhang in protecting against T2DM onset. Hyperglycemia was favorably suppressed by L. casei Zhang treatment. Moreover, the hyperglycemia was connected with type 1 immune response, high plasma bile acids and urine chloride ion loss. This chloride ion loss was significantly prevented by L. casei via upregulating of chloride ion-dependent genes (ClC1-7, GlyRalpha1, SLC26A3, SLC26A6, GABAAalpha1, Bestrophin-3 and CFTR). A shift in the caecal microflora, particularly the reduction of bile acid 7alpha-dehydroxylating bacteria, and fecal bile acid profiles also occurred. These change coincided with organ chloride influx. Thus, we postulate that the prevention of T2DM onset by L. casei Zhang may be via a microbiota-based bile acid-chloride exchange mechanism. PMID- 25133592 TI - Redox and metabolic regulation of stem/progenitor cells and their niche. AB - Stem cells are defined as cells that have the capacity to self-renew and exhibit multipotency or pluripotency, whereas progenitor cells are committed to selected lineages but retain their self-renewal capacity. The stem or progenitor cell niche refers to the microenvironment of the regenerative cells in the bone marrow (BM) or other tissues such as the heart. It can regulate self-renewal, differentiation, migration, and proliferation of regenerative stem/progenitor cells. The precise regulatory mechanisms by which the niche and the stem/progenitor cells interact are an active area of research. Reactive oxygen species (ROS) are one such niche regulatory mechanism. Quiescent stem cells in a hypoxic niche exhibit low ROS levels due to well-organized antioxidant defense systems, which protect stem cells from extrinsic oxidative stress, whereas high levels of ROS promote the differentiation or migration of stem/progenitor cells. In pathophysiological conditions such as diabetes, BM niche dysfunction induced by oxidative stress contributes to the reduction of the angiogenic and vasculogenic potential of BM-derived regenerative cells, thereby leading to less efficient healing and revascularization. Cells have evolved mechanisms to fine tune ROS levels by tightly regulated metabolic pathways such as glycolysis rather than oxidative phosphorylation to reduce oxidative stress. This Forum will summarize the recent progress regarding the redox and metabolic regulation of hematopoietic and cardiac stem/progenitor cells, as well as their niche interactions involved in tissue regeneration and repair under physiological and pathological conditions. Understanding such mechanisms will contribute to the development of novel therapeutic strategies to enhance regeneration and repair of diseased tissues. PMID- 25133593 TI - Synergistic and antagonistic effects of thermal shock, air exposure, and fishing capture on the physiological stress of Squilla mantis (Stomatopoda). AB - This study is aimed at assessing the effects of multiple stressors (thermal shock, fishing capture, and exposure to air) on the benthic stomatopod Squilla mantis, a burrowing crustacean quite widespread in the Mediterranean Sea. Laboratory analyses were carried out to explore the physiological impairment onset over time, based on emersion and thermal shocks, on farmed individuals. Parallel field-based studies were carried out to also investigate the role of fishing (i.e., otter trawling) in inducing physiological imbalance in different seasonal conditions. The dynamics of physiological recovery from physiological disruption were also studied. Physiological stress was assessed by analysing hemolymph metabolites (L-Lactate, D-glucose, ammonia, and H+), as well as glycogen concentration in muscle tissues. The experiments were carried out according to a factorial scheme considering the three factors (thermal shock, fishing capture, and exposure to air) at two fixed levels in order to explore possible synergistic, additive, or antagonistic effects among factors. Additive effects on physiological parameters were mainly detected when the three factors interacted together while synergistic effects were found as effect of the combination of two factors. This finding highlights that the physiological adaptive and maladaptive processes induced by the stressors result in a dynamic response that may encounter physiological limits when high stress levels are sustained. Thus, a further increase in the physiological parameters due to synergies cannot be reached. Moreover, when critical limits are encountered, mortality occurs and physiological parameters reflect the response of the last survivors. In the light of our mortality studies, thermal shock and exposure to air have the main effect on the survival of S. mantis only on trawled individuals, while lab-farmed individuals did not show any mortality during exposure to air until after 2 hours. PMID- 25133594 TI - Spontaneous high piezoelectricity in poly(vinylidene fluoride) nanoribbons produced by iterative thermal size reduction technique. AB - We produced kilometer-long, endlessly parallel, spontaneously piezoelectric and thermally stable poly(vinylidene fluoride) (PVDF) micro- and nanoribbons using iterative size reduction technique based on thermal fiber drawing. Because of high stress and temperature used in thermal drawing process, we obtained spontaneously polar gamma phase PVDF micro- and nanoribbons without electrical poling process. On the basis of X-ray diffraction (XRD) analysis, we observed that PVDF micro- and nanoribbons are thermally stable and conserve the polar gamma phase even after being exposed to heat treatment above the melting point of PVDF. Phase transition mechanism is investigated and explained using ab initio calculations. We measured an average effective piezoelectric constant as -58.5 pm/V from a single PVDF nanoribbon using a piezo evaluation system along with an atomic force microscope. PVDF nanoribbons are promising structures for constructing devices such as highly efficient energy generators, large area pressure sensors, artificial muscle and skin, due to the unique geometry and extended lengths, high polar phase content, high thermal stability and high piezoelectric coefficient. We demonstrated two proof of principle devices for energy harvesting and sensing applications with a 60 V open circuit peak voltage and 10 MUA peak short-circuit current output. PMID- 25133595 TI - Low-cost experimentation for the study of droplet microfluidics. AB - The continued growth of microfluidics into industry settings in areas such as point-of-care diagnostics and targeted therapeutics necessitates a workforce trained in microfluidic technologies and experimental methods. Laboratory courses for students at the university and high school levels will require cost-effective in-class demonstrations that instruct in chip design, fabrication, and experimentation at the microscale. We present a hand-operated pressure pumping system to form monodisperse picoliter to nanoliter droplet streams at low cost, and a series of exercises aimed at instructing in the specific art of droplet formation. Using this setup, the student is able to generate and observe the modes of droplet formation in flow-focusing devices, and the effect of device dimensions on the characteristics of formed droplets. Lastly, at ultra-low cost we demonstrate large plug formation in a T-junction using coffee stirrers as a master mold substitute. Our method reduces the cost of experimentation to enable intuitive instruction in droplet formation, with additional implications for creating droplets in the field or at point-of-care. PMID- 25133596 TI - Finite element study of human pelvis model in side impact for Chinese adult occupants. AB - OBJECTIVE: The occupant's pelvis is very vulnerable to side collision in road accidents. Finite element (FE) studies on pelvic injury help to design occupant protection devices to improve vehicle safety. This study was aimed to develop a highly biofidelic pelvis model of Chinese adults and assess its sensitivity to variations in pelvis cortical bone thickness, bone material properties, and loading conditions. METHODS: In this study, 4 different FE models of the pelvis were developed from the computed tomography (CT) data of a volunteer representing the 50th percentile Chinese male. Two of them were meshed using entirely hexahedral elements with variable and constant cortical thickness distribution (the V-Hex and C-Hex models), and the others were modeled with hexahedral elements for cancellous bone and variable or constant thickness shell elements for cortical bone (the V-HS and C-HS models). In model developments, the semi automatic multiblock meshing approach was employed to maintain the pelvis geometric curvature and generate a high-quality hexahedral mesh. Then, several simulations with postmortem human subjects (PMHS) tests were performed to obtain the most accurate model in predicting pelvic injury. Based on the most accurate model, sensitivity studies were conducted to analyze the effects of the cortex thickness, Young's modulus of the cortical and cancellous bone, impactor velocity, and impactor with or without padding on the biomechanical responses and injuries of pelvis. RESULTS: The results indicate that the models with variable cortical bone thickness can give more accurate predictions than those with constant cortical thickness. Both the V-Hex and V-HS models are favorable for simulating pelvic response and injury, but the simulation results of the V-Hex model agree with the tests better. The sensitivity study shows that pelvic response is more sensitive to alterations in the Young's modulus of cortical bone than cancellous bone. Compared to failure displacement, peak force is more sensitive to the cortical bone thickness. However, displacement is more sensitive to the Young's modulus of cancellous bone than peak force. The padding attached on the impactor plays a significant role in absorbing the impact energy and alleviating pelvic injury. CONCLUSIONS: The all-hex meshing method with variable cortical bone thickness has the highest accuracy but is time-consuming. The cortical bone plays a determining role in resisting pelvic fracture. Peak impact force appears to be a reasonable injury predictor for pelvic injury assessment. Some appropriate energy absorbers installed in the car door can significantly reduce pelvic injury and will be beneficial for occupant protection. PMID- 25133597 TI - What's new in shock? May 2014. PMID- 25133598 TI - The traumatic hemostasis and oxygenation research network remote damage control resuscitation (RDCR) symposium. PMID- 25133599 TI - Resuscitative endovascular balloon occlusion of the aorta: a gap analysis of severely injured UK combat casualties. AB - The control of torso and junctional zone bleeding in combat casualties is particularly challenging because of its noncompressible nature. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has demonstrated promise in translational large animal and early clinical series as an effective resuscitation and hemorrhage control adjunct. However, it is unknown what proportion of combat casualties has an injury pattern and clinical course that is amenable to REBOA deployment. The prospective UK Joint Theatre Trauma Registry was used to retrospectively identify all UK military personnel who has sustained a severe combat injury, defined as an Abbreviated Injury Scale of three or greater, in the course of 10 years. Patients were then divided into three groups based on Abbreviated Injury Scale injury pattern: no indications for REBOA, contraindications (mediastinal, cervical, and axillary hemorrhage), and indications (torso and pelvic hemorrhage). From a total of 1,317 patients, 925 (70.2%) had no indication, 148 (11.2%) had a contraindication, and 244 (18.5%) had an indication for REBOA. Within the group with indications for REBOA, there were 174 deaths: 79 at the point of wounding, 66 en route to hospital, and 29 in hospital deaths. The median (interquartile range) time to death in patients dying en route was 75 (42-109) min, and the median prehospital time for casualties admitted to hospital was 61 (34-89) min. One-in-five severely injured UK combat casualties have a focus of hemorrhage in the abdomen or pelvic junctional region potentially amenable to REBOA deployment. The UK military should explore REBOA as a potential en route hemorrhage control and resuscitation adjunct. PMID- 25133600 TI - Impact of body mass on outcomes of geriatric postoperative acute kidney injury patients. AB - BACKGROUND: Acute kidney injury (AKI) frequently occurs in hospitalized patients, particularly in the elderly. However, studies on outcome-modifying factors in geriatric patients with AKI are absent, especially the influence of body mass index (BMI). METHODS: We performed a retrospective analysis of a prospectively collected multicenter observational cohort, which enrolled elderly (>=65 years) who developed AKI after major surgery in the intensive care units. We analyzed in hospital mortality within BMI category utilizing Cox proportional hazard regression analysis and generalized additive modeling. RESULTS: Data of a total of 2,015 postoperative elderly patients were retrieved and analyzed. Generalized additive modeling showed that elderly AKI patients with a BMI between 21 and 31 kg/m(2) ("normal") had a lower mortality risk than those with a BMI of less than 21 kg/m(2) ("underweight") or 31 kg/m(2) or greater ("obese"). Both "underweight" and "obese" individuals had a greater risk of mortality compared with patients with "normal" BMI. CONCLUSIONS: The U-shaped association of BMI with hospital mortality in geriatric AKI patients contains a widened base and a shifted nadir comparing with chronic dialysis and other AKI patients. This finding is interesting and warrants our attention. PMID- 25133601 TI - Dried platelets in a swine model of liver injury. AB - INTRODUCTION: Lyophilization may facilitate production of a safe, portable, easily storable, and transportable source of platelets for bleeding patients. The objective of this study was to examine the impact of lyophilized human and porcine platelets in a swine liver injury model of nonsurgical hemorrhage. METHODS: Anesthetized pigs (40 kg) had a controlled 35% total blood volume bleed from the right jugular vein followed by cooling to 35 degrees C and resuscitation with Ringer's lactate to achieve a 3:1 blood withdrawal resuscitation. Through a midline laparotomy, the liver was injured with two standardized 5 * 5-cm grids with lacerations 1 cm apart and 0.5 cm deep. After 2 min of uncontrolled hemorrhage, the animals were treated with placebo (n = 5), lyophilized human (n = 5, HP), or swine platelets (n = 5, SP). At 15 min, shed blood was calculated. The animals then underwent abdominal closure. At 48 h, the animals were killed for histopathologic evaluation of the lung, kidney, and heart. RESULTS: Intraoperative blood loss at 15 min was significantly higher in the HP arm (SP: 4.9 +/- 2.9 mL/kg, HP: 12.3 +/- 4.7 mL/kg, and control: 6.1 +/- 2.5 mL/kg; P = 0.013). Mortality at 48 h was 20% in all three arms, due to uncontrolled intra abdominal bleeding. At the time the animals were killed, SP animals had a significantly higher hematocrit (SP: 22.0% +/- 3.0%, HP: 15.1% +/- 4.9%, and control: 13.9% +/- 0.6%; P = 0.026). No significant difference was found in platelet count (SP: 319.3 +/- 62.1 * 10(3)/uL, HP:361.5 +/- 133.6 * 10(3)/uL, and control: 242.7 +/- 42.5 * 10(3)/uL; P = 0.259). Histopathology of kidneys, lungs, and heart demonstrated no evidence of thromboembolic complications. CONCLUSION: In this swine model of liver injury, human lyophilized platelets increased intraoperative blood loss. With the use of species-specific lyophilized platelets, however, this effect was abolished, with a decrease in blood loss at 48 h after injury. PMID- 25133602 TI - Pleiotropic effects of atorvastatin in experimental sepsis: preservation of beta1 adrenoreceptor signaling in the heart. PMID- 25133603 TI - In situ chemical oxidation of contaminated groundwater by persulfate: decomposition by Fe(III)- and Mn(IV)-containing oxides and aquifer materials. AB - Persulfate (S2O8(2-)) is being used increasingly for in situ chemical oxidation (ISCO) of organic contaminants in groundwater, despite an incomplete understanding of the mechanism through which it is converted into reactive species. In particular, the decomposition of persulfate by naturally occurring mineral surfaces has not been studied in detail. To gain insight into the reaction rates and mechanism of persulfate decomposition in the subsurface, and to identify possible approaches for improving its efficacy, the decomposition of persulfate was investigated in the presence of pure metal oxides, clays, and representative aquifer solids collected from field sites in the presence and absence of benzene. Under conditions typical of groundwater, Fe(III)- and Mn(IV) oxides catalytically converted persulfate into sulfate radical (SO4(*-)) and hydroxyl radical (HO(*)) over time scales of several weeks at rates that were 2 20 times faster than those observed in metal-free systems. Amorphous ferrihydrite was the most reactive iron mineral with respect to persulfate decomposition, with reaction rates proportional to solid mass and surface area. As a result of radical chain reactions, the rate of persulfate decomposition increased by as much as 100 times when benzene concentrations exceeded 0.1 mM. Due to its relatively slow rate of decomposition in the subsurface, it can be advantageous to inject persulfate into groundwater, allowing it to migrate to zones of low hydraulic conductivity where clays, metal oxides, and contaminants will accelerate its conversion into reactive oxidants. PMID- 25133606 TI - Formulation, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles. AB - Abstract Context: Formulation, characterization, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles (SLMs). Objective: The objective of the study was to formulate and evaluate halofantrine-loaded SLMs. Materials and methods: Formulations of halofantrine-loaded SLMs were prepared by hot homogenization and thereafter lyophilized and characterized using particle size, pH stability, loading capacity (LC) and encapsulation efficiency (EE). In vitro release of halofantrine (Hf) from the optimized SLMs was performed in SIF and SGF. In vivo study using Peter's Four day suppressive protocol in mice and the mice thereafter subjected to histological studies in kidney and liver. Results: Results obtained indicated that EE of 76.32% and 61.43% were obtained for the SLMs containing 7% and 3% of Hf respectively. The SLMs loaded with 3% of Hf had the highest yield of 73.33%. Time-dependent pH stability analysis showed little variations in pH ranging from 3.49 +/- 0.04 to 4.03 +/- 0.05. Discussion: The SLMs showed pH-dependent release profile; in SIF (43.5% of the drug for each of H2 and H3) compared with SGF (13 and 18% for H2 and H3 respectively) after 8 h. The optimized SLMs formulation and Halfan(r) produced a percentage reduction in parasitemia of 72.96% and 85.71% respectively. The histological studies revealed that the SLMs formulations have no harmful effects on the kidney and liver. Conclusion: SLMs formulations might be an alternative for patients with parasitemia as there were no harmful effects on vital organs of the mice. PMID- 25133605 TI - Increased sensitivity to inflammatory pain induced by subcutaneous formalin injection in serine racemase knock-out mice. AB - D-Serine, an endogenous coagonist of the N-methyl-D-aspartate receptor (NMDAR), is widely distributed in the central nervous system and is synthesized from L serine by serine racemase (SR). NMDAR plays an important role in pain processing including central sensitization that eventually causes hyperalgesia. To elucidate the roles of D-serine and SR in pain transmission, we evaluated the behavioral changes and spinal nociceptive processing induced by formalin using SR knock-out (KO) mice. We found that SR is mainly distributed in lamina II of the dorsal horn of the spinal cord in wild-type (WT) mice. Although the formalin injected subcutaneously induced the biphasic pain response of licking in SR-KO and WT mice, the time spent on licking was significantly longer in the SR-KO mice during the second phase of the formalin test. The number of neurons immunopositive for c Fos and phosphorylated extracellular signal-regulated kinase (p-ERK), which are molecular pain markers, in laminae I-II of the ipsilateral dorsal horn was significantly larger in the SR-KO mice. Immunohistochemical staining revealed that the distribution of SR changed from being broad to being concentrated in cell bodies after the formalin injection. On the other hand, the expression level of the cytosolic SR in the ipsilateral dorsal horn significantly decreased. Oral administration of 10 mM D-serine in drinking water for one week cancelled the difference in pain behaviors between WT and SR-KO mice in phase 2 of the formalin test. These findings demonstrate that the SR-KO mice showed increased sensitivity to inflammatory pain and the WT mice showed translocation of SR and decreased SR expression levels after the formalin injection, which suggest a novel antinociceptive mechanism via SR indicating an important role of D-serine in pain transmission. PMID- 25133604 TI - Curation and analysis of multitargeting agents for polypharmacological modeling. AB - In drug discovery and development, the conventional "single drug, single target" concept has been shifted to "single drug, multiple targets"--a concept coined as polypharmacology. For studies in this emerging field, dedicated and high-quality databases of multitargeting ligands would be exceedingly beneficial. To this end, we conducted a comprehensive analysis of the structural and chemical/biological profiles of polypharmacological agents and present a Web-based database (Polypharma). All of these compounds curated herein have been cocrystallized with more than one unique protein with intensive reports of their multitargeting activities. The present study provides more insight of drug multitargeting and is particularly useful for polypharmacology modeling. This specialized curation has been made publically available at http:/imdlab.org/polypharma/ PMID- 25133607 TI - Addressing mechanism of fibrillization/aggregation and its prevention in presence of osmolytes: spectroscopic and calorimetric approach. AB - Understanding the mechanism of protein fibrillization/aggregation and its prevention is the basis of development of therapeutic strategies for amyloidosis. An attempt has been made to understand the nature of interactions of osmolytes L proline, 4-hydroxy-L-proline, sarcosine and trimethylamine N-oxide with the different stages of fibrillization of hen egg-white lysozyme by using a combination of isothermal titration calorimetry, differential scanning calorimetry, fluorescence spectroscopy, and transmission electron microscopy. Based on thioflavin T fluorescence emission intensities and microscopic images, the nucleation, elongation, and saturation phases of fibrillization have been identified. Isothermal titration calorimetry and differential scanning calorimetry have enabled a quantitative analysis of the nature of interactions of these osmolytes with various conformational states of lysozyme at different stages of fibrillization/aggregation. It is concluded that interaction of the osmolytes with lysozyme fibrils at both the nucleation and elongation stages are important steps in the prevention of fibrillization/aggregation. Identification of the nature of interactions is a key step towards the discovery and synthesis of target oriented potential inhibitors of these associations. This study is a first report in which calorimetry has been used to address interaction of potential inihibitiors with the protein at different stages of fibrillization. PMID- 25133608 TI - Precise engineering of siRNA delivery vehicles to tumors using polyion complexes and gold nanoparticles. AB - For systemic delivery of siRNA to solid tumors, a size-regulated and reversibly stabilized nanoarchitecture was constructed by using a 20 kDa siRNA-loaded unimer polyion complex (uPIC) and 20 nm gold nanoparticle (AuNP). The uPIC was selectively prepared by charge-matched polyionic complexation of a poly(ethylene glycol)-b-poly(L-lysine) (PEG-PLL) copolymer bearing ~40 positive charges (and thiol group at the omega-end) with a single siRNA bearing 40 negative charges. The thiol group at the omega-end of PEG-PLL further enabled successful conjugation of the uPICs onto the single AuNP through coordinate bonding, generating a nanoarchitecture (uPIC-AuNP) with a size of 38 nm and a narrow size distribution. In contrast, mixing thiolated PEG-PLLs and AuNPs produced a large aggregate in the absence of siRNA, suggesting the essential role of the preformed uPIC in the formation of nanoarchitecture. The smart uPIC-AuNPs were stable in serum-containing media and more resistant against heparin-induced counter polyanion exchange, compared to uPICs alone. On the other hand, the treatment of uPIC-AuNPs with an intracellular concentration of glutathione substantially compromised their stability and triggered the release of siRNA, demonstrating the reversible stability of these nanoarchitectures relative to thiol exchange and negatively charged AuNP surface. The uPIC-AuNPs efficiently delivered siRNA into cultured cancer cells, facilitating significant sequence-specific gene silencing without cytotoxicity. Systemically administered uPIC-AuNPs showed appreciably longer blood circulation time compared to controls, i.e., bare AuNPs and uPICs, indicating that the conjugation of uPICs onto AuNP was crucial for enhancing blood circulation time. Finally, the uPIC-AuNPs efficiently accumulated in a subcutaneously inoculated luciferase-expressing cervical cancer (HeLa-Luc) model and achieved significant luciferase gene silencing in the tumor tissue. These results demonstrate the strong potential of uPIC-AuNP nanoarchitectures for systemic siRNA delivery to solid tumors. PMID- 25133610 TI - Mobile phones: the next step towards healthcare delivery in rural India? AB - BACKGROUND: Given the ubiquity of mobile phones, their use to support healthcare in the Indian context is inevitable. It is however necessary to assess end-user perceptions regarding mobile health interventions especially in the rural Indian context prior to its use in healthcare. This would contextualize the use of mobile phone communication for health to 70% of the country's population that resides in rural India. OBJECTIVES: To explore the acceptability of delivering healthcare interventions through mobile phones among users in a village in rural Bangalore. METHODS: This was an exploratory study of 488 mobile phone users, residing in a village, near Bangalore city, Karnataka, South India. A pretested, translated, interviewer-administered questionnaire was used to obtain data on mobile phone usage patterns and acceptability of the mobile phone, as a tool for health-related communication. The data is described using basic statistical measures. RESULTS: The primary use of mobile phones was to make or receive phone calls (100%). Text messaging (SMS) was used by only 70 (14%) of the respondents. Most of the respondents, 484 (99%), were willing to receive health-related information on their mobile phones and did not consider receiving such information, an intrusion into their personal life. While receiving reminders for drug adherence was acceptable to most 479 (98%) of our respondents, 424 (89%) preferred voice calls alone to other forms of communication. Nearly all were willing to use their mobile phones to communicate with health personnel in emergencies and 367 (75%) were willing to consult a doctor via the phone in an acute illness. Factors such as sex, English literacy, employment status, and presence of chronic disease affected preferences regarding mode and content of communication. CONCLUSION: The mobile phone, as a tool for receiving health information and supporting healthcare through mHealth interventions was acceptable in the rural Indian context. PMID- 25133611 TI - Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during T cell migration. AB - Chemokines promote T cell migration by transmitting signals that induce T cell polarization and integrin activation and adhesion. Mst1 kinase is a key signal mediator required for both of these processes; however, its molecular mechanism remains unclear. Here, we present a mouse model in which Mst1 function is disrupted by a hypomorphic mutation. Microscopic analysis of Mst1-deficient CD4 T cells revealed a necessary role for Mst1 in controlling the localization and activity of Myosin IIa, a molecular motor that moves along actin filaments. Using affinity specific LFA-1 antibodies, we identified a requirement for Myosin IIa dependent contraction in the precise spatial distribution of low and higher affinity LFA-1 on the membrane of migrating T cells. Mst1 deficiency or Myosin inhibition resulted in multipolar cells, difficulties in uropod detachment and mis-localization of low affinity LFA-1. Thus, Mst1 regulates Myosin IIa dynamics to organize high and low affinity LFA-1 to the anterior and posterior membrane during T cell migration. PMID- 25133612 TI - Experimental virus evolution reveals a role of plant microtubule dynamics and TORTIFOLIA1/SPIRAL2 in RNA trafficking. AB - The cytoskeleton is a dynamic network composed of filamentous polymers and regulatory proteins that provide a flexible structural scaffold to the cell and plays a fundamental role in developmental processes. Mutations that alter the spatial orientation of the cortical microtubule (MT) array of plants are known to cause important changes in the pattern of cell wall synthesis and developmental phenotypes; however, the consequences of such alterations on other MT-network associated functions in the cytoplasm are not known. In vivo observations suggested a role of cortical MTs in the formation and movement of Tobacco mosaic virus (TMV) RNA complexes along the endoplasmic reticulum (ER). Thus, to probe the significance of dynamic MT behavior in the coordination of MT-network associated functions related to TMV infection and, thus, in the formation and transport of RNA complexes in the cytoplasm, we performed an evolution experiment with TMV in Arabidopsis thaliana tor1/spr2 and tor2 mutants with specific defects in MT dynamics and asked whether TMV is sensitive to these changes. We show that the altered cytoskeleton induced genetic changes in TMV that were correlated with efficient spread of infection in the mutant hosts. These observations demonstrate a role of dynamic MT rearrangements and of the MT-associated protein TORTIFOLIA1/SPIRAL2 in cellular functions related to virus spread and indicate that MT dynamics and MT-associated proteins represent constraints for virus evolution and adaptation. The results highlight the importance of the dynamic plasticity of the MT network in directing cytoplasmic functions in macromolecular assembly and trafficking and illustrate the value of experimental virus evolution for addressing the cellular functions of dynamic, long-range order systems in multicellular organisms. PMID- 25133616 TI - Cautionary case: low Glasgow Coma Scale scores, brainstem involvement, decompressive craniectomy, full recovery, and one more reason for advocacy/collaboration. AB - Presurgical selection criteria for decompressive craniectomy (DC) for treatment of severe traumatic brain injury remain controversial. Proposed criteria to improve outcomes include high admission Glasgow Coma Scale scores (>=7) and exclusion of patients having brainstem involvement. Neurosurgeons may be unaware of long-term functional outcomes in their DC patients. Therefore, to underscore an exceptional outcome that may have been facilitated by DC, while highlighting need for caution in development of potentially overly restrictive presurgical selection criteria, this case report of a 21-yr-old premed college student admitted with severe traumatic brain injury, Glasgow Coma Scale score of 3, left fixed dilated pupil, and brainstem signs, who had emergency DC, is presented. Nine years after the trauma, she was employed full time as a physician, and only residual symptom, an occasional headache, remained. Thus, caution is necessary in the development of DC presurgical selection guidelines, as this case had excellent long-term functional outcome that may have been facilitated by DC despite initial low Glasgow Coma Scale scores and signs of brainstem involvement. Also, this case highlights one more reason for multispecialty physician advocacy, collaboration, and comparative effectiveness research. PMID- 25133615 TI - Barriers to early mobility of hospitalized general medicine patients: survey development and results. AB - OBJECTIVE: Functional status decline commonly accompanies hospitalization making patients vulnerable to complications. Such decline can be mitigated through hospital-based early mobility programs. Success in implementing patient mobility quality improvement processes requires evaluating providers' knowledge, attitudes, and behaviors. DESIGN: A cross-sectional, self-administered survey in two different hospital settings was completed by 120 nurses and physical and occupational therapists (rehabilitation therapists, 38; nurses, 82) from six general medicine units. The survey was developed using published guidelines, literature review, and provider meetings and refined through pilot testing. Psychometric properties were assessed, and regression analyses were conducted to examine barriers to early mobility by hospital site, provider discipline, and years of experience. RESULTS: Internal consistency reliability, item consistency, and discriminant validity psychometric characteristics were acceptable. In multivariable regression analysis, overall perceived barriers were similar between the two hospitals (P = 0.25) and significantly higher for staff with less experience (P = 0.02) and for nurses vs. rehabilitation therapists (P < 0.001).The survey identified specific barriers common to both nurses and rehabilitation therapists and other barriers that were discipline specific. CONCLUSIONS: This novel survey identified important barriers to mobilizing medical inpatients that were similar across two hospital settings. These results can assist with the implementation of quality improvement projects for increasing early hospital-based patient mobility. PMID- 25133613 TI - Targeted next-generation sequencing reveals novel USH2A mutations associated with diverse disease phenotypes: implications for clinical and molecular diagnosis. AB - USH2A mutations have been implicated in the disease etiology of several inherited diseases, including Usher syndrome type 2 (USH2), nonsyndromic retinitis pigmentosa (RP), and nonsyndromic deafness. The complex genetic and phenotypic spectrums relevant to USH2A defects make it difficult to manage patients with such mutations. In the present study, we aim to determine the genetic etiology and to characterize the correlated clinical phenotypes for three Chinese pedigrees with nonsyndromic RP, one with RP sine pigmento (RPSP), and one with USH2. Family histories and clinical details for all included patients were reviewed. Ophthalmic examinations included best corrected visual acuities, visual field measurements, funduscopy, and electroretinography. Targeted next-generation sequencing (NGS) was applied using two sequence capture arrays to reveal the disease causative mutations for each family. Genotype-phenotype correlations were also annotated. Seven USH2A mutations, including four missense substitutions (p.P2762A, p.G3320C, p.R3719H, and p.G4763R), two splice site variants (c.8223+1G>A and c.8559-2T>C), and a nonsense mutation (p.Y3745*), were identified as disease causative in the five investigated families, of which three reported to have consanguineous marriage. Among all seven mutations, six were novel, and one was recurrent. Two homozygous missense mutations (p.P2762A and p.G3320C) were found in one individual family suggesting a potential double hit effect. Significant phenotypic divergences were revealed among the five families. Three families of the five families were affected with early, moderated, or late onset RP, one with RPSP, and the other one with USH2. Our study expands the genotypic and phenotypic variability relevant to USH2A mutations, which would help with a clear insight into the complex genetic and phenotypic spectrums relevant to USH2A defects, and is complementary for a better management of patients with such mutations. We have also demonstrated that a targeted NGS approach is a valuable tool for the genetic diagnosis of USH2 and RP. PMID- 25133614 TI - Is thymidine glycol containing DNA a substrate of E. coli DNA mismatch repair system? AB - The DNA mismatch repair (MMR) system plays a crucial role in the prevention of replication errors and in the correction of some oxidative damages of DNA bases. In the present work the most abundant oxidized pyrimidine lesion, 5,6-dihydro-5,6 dihydroxythymidine (thymidine glycol, Tg) was tested for being recognized and processed by the E. coli MMR system, namely complex of MutS, MutL and MutH proteins. In a partially reconstituted MMR system with MutS-MutL-MutH proteins, G/Tg and A/Tg containing plasmids failed to provoke the incision of DNA. Tg residue in the 30-mer DNA duplex destabilized double helix due to stacking disruption with neighboring bases. However, such local structural changes are not important for E. coli MMR system to recognize this lesion. A lack of repair of Tg containing DNA could be due to a failure of MutS (a first acting protein of MMR system) to interact with modified DNA in a proper way. It was shown that Tg in DNA does not affect on ATPase activity of MutS. On the other hand, MutS binding affinities to DNA containing Tg in G/Tg and A/Tg pairs are lower than to DNA with a G/T mismatch and similar to canonical DNA. Peculiarities of MutS interaction with DNA was monitored by Forster resonance energy transfer (FRET) and fluorescence anisotropy. Binding of MutS to Tg containing DNAs did not result in the formation of characteristic DNA kink. Nevertheless, MutS homodimer orientation on Tg-DNA is similar to that in the case of G/T-DNA. In contrast to G/T-DNA, neither G/Tg- nor A/Tg-DNA was able to stimulate ADP release from MutS better than canonical DNA. Thus, Tg residue in DNA is unlikely to be recognized or processed by the E. coli MMR system. Probably, the MutS transformation to active "sliding clamp" conformation on Tg-DNA is problematic. PMID- 25133617 TI - Swallowing appliance: intraoral reshaping prosthesis for dysphagia secondary to oral floor cancer: a pilot study. AB - Patients with oral floor cancer often have difficulty swallowing solid foods. The aim of this study was to improve the propulsion of solid foods using a swallowing appliance (SW-A). Subjects comprised three patients with oral floor cancer who had undergone curative surgery. Each participant was asked to swallow gelatin under three conditions: without an SW-A, with a maxillary SW-A, and with both maxillary and mandibular SW-As. This procedure was repeated thrice with three volumes of gelatin (2.5, 5, and 7.5 ml), with videofluorographic swallowing study. Swallowing was assessed on the basis of whether the participant could propel the gelatin from the oral cavity to the pharynx. No subject could propel 2.5 ml of gelatin to the pharynx without an SW-A or with only a maxillary SW-A in place. When both SW-As were used, all subjects could propel all three volumes of gelatin. The mandibular SW-A complemented the compensatory effects of the maxillary SW-A. PMID- 25133618 TI - Affective state and community integration after traumatic brain injury. AB - Previous studies investigating the relationship between affective state and community integration have focused primarily on the influence of depression and anxiety. In addition, they have focused on frequency of participation in various activities, failing to address an individual's subjective satisfaction with participation. The purpose of this study was to examine how affective state contributes to frequency of participation and satisfaction with participation after traumatic brain injury among participants with and without a current major depressive episode. Sixty-four community-dwelling participants with a history of complicated mild-to-severe traumatic brain injury participated in this cross sectional cohort study. High positive affect contributed significantly to frequency of participation (beta = 0.401, P = 0.001), and both high positive affect and low negative affect significantly contributed to better satisfaction with participation (F2,61 = 13.63, P < 0.001). Further investigation to assess the direction of these relationships may better inform effective targets for intervention. These findings highlight the importance of assessing affective state after traumatic brain injury and incorporating a subjective measure of participation when considering community integration outcomes. PMID- 25133619 TI - Pneumocephalus during cervical transforaminal epidural steroid injections: a case report. AB - A cervical transforaminal epidural injection of anesthetic and corticosteroids (CTFESI) is a frequently used procedure for cervical radiculopathy. Most cases of pneumocephalus after an epidural block occur when using an interlaminar approach with the loss-of-resistance technique. The authors present the first case of pneumocephalus after cervical transforaminal epidural injection of anesthetic and corticosteroids. A 64-yr-old woman with left C7 radiculopathy was undergoing C6-7 transforaminal epidural injection of anesthetic and corticosteroids. The epidural spread of contrast was checked by fluoroscope, and 5 mg of dexamethasone in 4 ml of 0.1875% ropivacaine was injected. She lost consciousness 5 mins after the procedure and regained awareness after manual ventilation. She subsequently complained of nausea and headache, and a computed tomography brain scan revealed pneumocephalus. After carefully assessing the fluoroscopic images, the authors believe that the needle may have punctured the dura mater of the nerve root sleeve, allowing air to enter the subdural space. Thus, fluoroscopic images should be carefully examined to reduce dural puncture when performing cervical transforaminal epidural injection of anesthetic and corticosteroids, and air should be completely removed from the needle, extension tube, and syringe. PMID- 25133620 TI - Clinical tests of ankle plantarflexor strength do not predict ankle power generation during walking. AB - OBJECTIVE: The aim of this study was to investigate the relationship between a clinical test of ankle plantarflexor strength and ankle power generation (APG) at push-off during walking. DESIGN: This is a prospective cross-sectional study of 102 patients with traumatic brain injury. OUTCOME MEASURES: Handheld dynamometry was used to measure ankle plantarflexor strength. Three-dimensional gait analysis was performed to quantify ankle power generation at push-off during walking. RESULTS: Ankle plantarflexor strength was only moderately correlated with ankle power generation at push-off (r = 0.43, P < 0.001; 95% confidence interval, 0.26 0.58). There was also a moderate correlation between ankle plantarflexor strength and self-selected walking velocity (r = 0.32, P = 0.002; 95% confidence interval, 0.13-0.48). CONCLUSIONS: Handheld dynamometry measures of ankle plantarflexor strength are only moderately correlated with ankle power generation during walking. This clinical test of ankle plantarflexor strength is a poor predictor of calf muscle function during gait in people with traumatic brain injury. PMID- 25133621 TI - Congenital agenesis of the superficial posterior compartment calf muscles in a 13 month-old infant. AB - Muscle agenesis may induce cosmetic and functional deficits, particularly if the muscle is an axial limb or a large muscle. Limb muscle agenesis is a rare condition. Here, the authors report the case of a 13-mo-old girl with unilateral atrophic calf and gait abnormality. Magnetic resonance imaging confirmed agenesis of the posterior superficial compartment of the calf. The patient showed an out toeing calcaneal gait and fibular length discrepancy secondarily during growth. Normal embryology and the differential diagnostic point of foot deformity as well as the clinical implications of calf agenesis are described. PMID- 25133622 TI - Gluteus maximus calcific tendonosis: a rare cause of sciatic pain. AB - Extraspinal causes of radicular pain are rare and are in danger of being overlooked. Here, we present a patient with pain radiating into the posterior thigh and lateral calf. Although initial differential diagnosis included lumbar herniated nucleus pulposus, further imaging revealed the presence of gluteus maximus calcific tendonosis. After physical therapy and a potent oral steroid regimen, the pain gradually resolved and the patient was able to return to full activity. PMID- 25133625 TI - Myasthenis gravis or Lambert-Eaton myasthenic syndrome? PMID- 25133624 TI - Targeted rehabilitation after extracellular matrix scaffold transplantation for the treatment of volumetric muscle loss. AB - Rehabilitation therapy is an important aspect of recovery after volumetric muscle loss. However, the traditional rehabilitation approach involves a period of rest and passive loading followed by gradual active loading. Extracellular matrix is a naturally occurring material consisting of structural proteins that provide mechanical strength, structural support, and functional molecules with diverse bioactive properties. There is evidence to suggest that the addition of aggressive regenerative rehabilitation protocols immediately after surgical implantation of an extracellular matrix scaffold to an area of volumetric muscle loss has significant benefits for extracellular matrix remodeling. Rehabilitation exercises likely provide the needed mechanical signals to encourage cell migration and site-specific differentiation in the temporal framework required for constructive remodeling. Herein, the authors review the literature and present an example of an aggressive rehabilitation program implemented immediately after extracellular matrix transplantation into a severely injured quadriceps muscle. PMID- 25133623 TI - Allogeneic Articular Chondrocyte Transplantation Downregulates Interleukin 8 Gene Expression in the Degenerating Rabbit Intervertebral Disk In Vivo. AB - OBJECTIVE: The aim of this study was to investigate whether repopulating the degenerating intervertebral disk (IVD) with articular chondrocytes will decrease inflammation in the degenerating rabbit IVD. DESIGN: This was a biologic study in a rabbit IVD-injury model in vivo. Dual cell tracking methods (infrared dye labeling and adenovirus transduction) were used to demonstrate the viability of allogeneic articular chondrocytes injected into degenerating rabbit IVDs. Interleukin 8 gene expression was determined via real-time polymerase chain reaction. Infiltrating inflammatory cells (macrophages, T cells, or neutrophils) were examined with immunohistochemistry. The IVDs were also examined by routine histology. RESULTS: Articular chondrocytes labeled with infrared dye were detected in the degenerating IVDs at both 2 and 8 wks after injection. At the 2 wk time point, interleukin 8 gene expression was comparable in IVDs injected with chondrocytes and in intact disks as control (P = 0.647), whereas its expression in IVDs injected with saline increased 50-fold (P = 0.028). Transgene expression of red fluorescent protein, beta-galactosidase, and human bone morphogenetic protein 7 diminished at 8 wks after injection. IVDs injected with chondrocytes overexpressing human bone morphogenetic protein 7 did not show lower interleukin 8 gene expression or improved histology. Macrophages were consistently detected by immunohistochemistry in the cartilage formed around the needle insertion sites in both the saline and chondrocyte groups, whereas neither T cells nor neutrophils were detected. CONCLUSIONS: Allogeneic rabbit articular chondrocyte survived in the degenerating rabbit IVDs for at least 8 wks. Cell treatment resulted in reduced IVD inflammation but did not significantly improve IVD structure. PMID- 25133628 TI - Fluoride free synthesis of anatase TiO2 nanocrystals with exposed active {001} facets. AB - A novel fluoride free protocol for highly truncated anatase TiO2 nanocrystals with exposed {001} facets by preferential adsorption of CO3(2-) ions is developed. Experimental observations were corroborated by first principle quantum chemical DFT calculations. The synthesized anatase TiO2 showed improved photocatalytic activity. PMID- 25133626 TI - Hope for successful implementation of psychosocial/psychiatric rehabilitation in the forensic mental health setting. AB - OBJECTIVE: To explore staff perceptions of the successes and barriers to implementation of the psychosocial/psychiatric rehabilitation (PSR) model in the forensic mental health setting and identify staff supports needed for greater implementation. METHOD: A qualitative descriptive design was used and staff focus group data was analyzed using the constant comparative method. RESULTS: All aspects of PSR are being implemented in the forensic setting. Barriers limiting comprehensive implementation include hospital processes and functions, legal components, client clinical presentation, staff attributes and interactions, and lack of resources. To foster greater implementation, employees require support to improve interprofessional interactions and acquire additional resources and education. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Strengthening existing successes and addressing barriers identified will foster greater PSR implementation in the forensic setting. Adjusting the physical environment, streamlining documentation, shifting focus from security to rehabilitation goals, and adapting PSR principles to various levels of illness acuity and stages of treatment would enhance PSR implementation. A management focus on improving staff morale, self-care, peer support, team cohesion, and communication would limit burnout and increase successful implementation of PSR. Additional educational opportunities and ongoing training are suggested to support a unified understanding and sustained approach to PSR implementation in the forensic setting. PMID- 25133627 TI - Nuclear translocation of hARD1 contributes to proper cell cycle progression. AB - Arrest defective 1 (ARD1) is an acetyltransferase that is highly conserved across organisms, from yeasts to humans. The high homology and widespread expression of ARD1 across multiple species and tissues signify that it serves a fundamental role in cells. Human ARD1 (hARD1) has been suggested to be involved in diverse biological processes, and its role in cell proliferation and cancer development has been recently drawing attention. However, the subcellular localization of ARD1 and its relevance to cellular function remain largely unknown. Here, we have demonstrated that hARD1 is imported to the nuclei of proliferating cells, especially during S phase. Nuclear localization signal (NLS)-deleted hARD1 (hARD1DeltaN), which can no longer access the nucleus, resulted in cell morphology changes and cellular growth impairment. Notably, hARD1DeltaN expressing cells showed alterations in the cell cycle and the expression levels of cell cycle regulators compared to hARD1 wild-type cells. Furthermore, these effects were rescued when the nuclear import of hARD1 was restored by exogenous NLS. Our results show that hARD1 nuclear translocation mediated by NLS is required for cell cycle progression, thereby contributing to proper cell proliferation. PMID- 25133629 TI - The cybotactic nematic phase of bent-core mesogens: state of the art and future developments. AB - The molecular clustering observed in the fluid nematic phase of nonlinear liquid crystal molecules underlies exaggerated field effects that portend unique technological advances in next-generation liquid crystal displays. However, the detailed nature of the molecular organization within the clusters and the temporal and spatial persistence of the organization remain unclear. Herein we review the evolution of structural studies of this unique nematic phase. The mounting experimental evidence points to a converging picture of the microscopic nature of this relatively new class of liquid crystals. PMID- 25133631 TI - Region-specific sensitivity of anemophilous pollen deposition to temperature and precipitation. AB - Understanding relations between climate and pollen production is important for several societal and ecological challenges, importantly pollen forecasting for pollinosis treatment, forensic studies, global change biology, and high resolution palaeoecological studies of past vegetation and climate fluctuations. For these purposes, we investigate the role of climate variables on annual-scale variations in pollen influx, test the regional consistency of observed patterns, and evaluate the potential to reconstruct high-frequency signals from sediment archives. A 43-year pollen-trap record from the Netherlands is used to investigate relations between annual pollen influx, climate variables (monthly and seasonal temperature and precipitation values), and the North Atlantic Oscillation climate index. Spearman rank correlation analysis shows that specifically in Alnus, Betula, Corylus, Fraxinus, Quercus and Plantago both temperature in the year prior to (T-1), as well as in the growing season (T), are highly significant factors (TApril rs between 0.30 [P<0.05[ and 0.58 [P<0.0001]; TJuli-1 rs between 0.32 [P<0.05[ and 0.56 [P<0.0001]) in the annual pollen influx of wind-pollinated plants. Total annual pollen prediction models based on multiple climate variables yield R2 between 0.38 and 0.62 (P<0.0001). The effect of precipitation is minimal. A second trapping station in the SE Netherlands, shows consistent trends and annual variability, suggesting the climate factors are regionally relevant. Summer temperature is thought to influence the formation of reproductive structures, while temperature during the flowering season influences pollen release. This study provides a first predictive model for seasonal pollen forecasting, and also aides forensic studies. Furthermore, variations in pollen accumulation rates from a sub-fossil peat deposit are comparable with the pollen trap data. This suggests that high frequency variability pollen records from natural archives reflect annual past climate variability, and can be used in palaeoecological and -climatological studies to bridge between population- and species-scale responses to climate forcing. PMID- 25133630 TI - Evaluation of antimalarial activity and toxicity of a new primaquine prodrug. AB - Plasmodium vivax is the most prevalent of the five species causing malaria in humans. The current available treatment for P. vivax malaria is limited and unsatisfactory due to at least two drawbacks: the undesirable side effects of primaquine (PQ) and drug resistance to chloroquine. Phenylalanine-alanine-PQ (Phe Ala-PQ) is a PQ prodrug with a more favorable pharmacokinetic profile compared to PQ. The toxicity of this prodrug was evaluated in in vitro assays using a human hepatoma cell line (HepG2), a monkey kidney cell line (BGM), and human red blood cells deficient in the enzyme glucose-6-phosphate-dehydrogenase (G6PD). In addition, in vivo toxicity assays were performed with rats that received multiple doses of Phe-Ala-PQ to evaluate biochemical, hematological, and histopathological parameters. The activity was assessed by the inhibition of the sporogonic cycle using a chicken malaria parasite. Phe-Ala-PQ blocked malaria transmission in Aedes mosquitoes. When compared with PQ, it was less cytotoxic to BGM and HepG2 cells and caused less hemolysis of G6PD-deficient red blood cells at similar concentrations. The prodrug caused less alteration in the biochemical parameters than did PQ. Histopathological analysis of the liver and kidney did show differences between the control and Phe-Ala-PQ-treated groups, but they were not statistically significant. Taken together, the results highlight the prodrug as a novel lead compound candidate for the treatment of P. vivax malaria and as a blocker of malaria transmission. PMID- 25133634 TI - De novo design of self-assembled hexapeptides as beta-amyloid (Abeta) peptide inhibitors. AB - The ability of peptides to construct specific secondary structures provides a useful function for biomaterial design that cannot be achieved with traditional organic molecules and polymers. Inhibition of amyloid formation is a promising therapeutic approach for the treatment of neurodegenerative diseases. Existing peptide-based inhibitors are mainly derived from original amyloid sequences, which have very limited sequence diversity and activity. It is highly desirable to explore other peptide-based inhibitors that are not directly derived from amyloid sequences. Here, we develop a hybrid high-throughput computational method to efficiently screen and design hexapeptide inhibitors against amyloid-beta (Abeta) aggregation and toxicity from the first principle. Computationally screened/designed inhibitors are then validated for their inhibition activity using biophysical experiments. We propose and demonstrate a proof-of-concept of the "like-interacts-like" design principle that the self-assembling peptides are able to interact strongly with conformationally similar motifs of Abeta peptides and to competitively reduce Abeta-Abeta interactions, thus preventing Abeta aggregation and Abeta-induced toxicity. Such a de novo design can also be generally applicable to design new peptide inhibitors against other amyloid diseases, beyond traditional peptide inhibitors with homologous sequences to parent amyloid peptides. PMID- 25133632 TI - A conserved cysteine residue of Bacillus subtilis SpoIIIJ is important for endospore development. AB - During sporulation in Bacillus subtilis, the onset of activity of the late forespore-specific sigma factor sigmaG coincides with completion of forespore engulfment by the mother cell. At this stage, the forespore becomes a free protoplast, surrounded by the mother cell cytoplasm and separated from it by two membranes that derive from the asymmetric division septum. Continued gene expression in the forespore, isolated from the surrounding medium, relies on the SpoIIIA-SpoIIQ secretion system assembled from proteins synthesised both in the mother cell and in the forespore. The membrane protein insertase SpoIIIJ, of the YidC/Oxa1/Alb3 family, is involved in the assembly of the SpoIIIA-SpoIIQ complex. Here we show that SpoIIIJ exists as a mixture of monomers and dimers stabilised by a disulphide bond. We show that residue Cys134 within transmembrane segment 2 (TM2) of SpoIIIJ is important to stabilise the protein in the dimeric form. Labelling of Cys134 with a Cys-reactive reagent could only be achieved under stringent conditions, suggesting a tight association at least in part through TM2, between monomers in the membrane. Substitution of Cys134 by an Ala results in accumulation of the monomer, and reduces SpoIIIJ function in vivo. Therefore, SpoIIIJ activity in vivo appears to require dimer formation. PMID- 25133637 TI - Genome-wide association studies and heritability estimates of body mass index related phenotypes in Bangladeshi adults. AB - Many health outcomes are influenced by a person's body mass index, as well as by the trajectory of body mass index through a lifetime. Although previous research has established that body mass index related traits are influenced by genetics, the relationship between these traits and genetics has not been well characterized in people of South Asian ancestry. To begin to characterize this relationship, we analyzed the association between common genetic variation and five phenotypes related to body mass index in a population-based sample of 5,354 Bangladeshi adults. We discovered a significant association between SNV rs347313 (intron of NOS1AP) and change in body mass index in women over two years. In a linear mixed-model, the G allele was associated with an increase of 0.25 kg/m2 in body mass index over two years (p-value of 2.3.10-8). We also estimated the heritability of these phenotypes from our genotype data. We found significant estimates of heritability for all of the body mass index-related phenotypes. Our study evaluated the genetic determinants of body mass index related phenotypes for the first time in South Asians. The results suggest that these phenotypes are heritable and some of this heritability is driven by variation that differs from those previously reported. We also provide evidence that the genetic etiology of body mass index related traits may differ by ancestry, sex, and environment, and consequently that these factors should be considered when assessing the genetic determinants of the risk of body mass index-related disease. PMID- 25133638 TI - Assessment of species diversity and distribution of an ancient diatom lineage using a DNA metabarcoding approach. AB - BACKGROUND: Continuous efforts to estimate actual diversity and to trace the species distribution and ranges in the natural environments have gone in equal pace with advancements of the technologies in the study of microbial species diversity from microscopic observations to DNA-based barcoding. DNA metabarcoding based on Next Generation Sequencing (NGS) constitutes the latest advancement in these efforts. Here we use NGS data from different sites to investigate the geographic range of six species of the diatom family Leptocylindraceae and to identify possible new taxa within the family. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the V4 and V9 regions of the nuclear-encoded SSU rDNA gene region in the NGS database of the European ERA-Biodiversa project BioMarKs, collected in plankton and sediments at six coastal sites in European coastal waters, as well as environmental sequences from the NCBI database. All species known in the family Leptocylindraceae were detected in both datasets, but the much larger Illumina V9 dataset showed a higher species coverage at the various sites than the 454 V4 dataset. Sequences identical or similar to the references of Leptocylindrus aporus, L. convexus, L. danicus/hargravesii and Tenuicylindrus belgicus were found in the Mediterranean Sea, North Atlantic Ocean and Black Sea as well as at locations outside Europe. Instead, sequences identical or close to that of L. minimus were found in the North Atlantic Ocean and the Black Sea but not in the Mediterranean Sea, while sequences belonging to a yet undescribed taxon were encountered only in Oslo Fjord and Baffin Bay. CONCLUSIONS/SIGNIFICANCE: Identification of Leptocylindraceae species in NGS datasets has expanded our knowledge of the species biogeographic distribution and of the overall diversity of this diatom family. Individual species appear to be widespread, but not all of them are found everywhere. Despite the sequencing depth allowed by NGS and the wide geographic area covered by this study, the diversity of this ancient diatom family appears to be low, at least at the level of the marker used in this study. PMID- 25133636 TI - The molecular phenotype of endocapillary proliferation: novel therapeutic targets for IgA nephropathy. AB - IgA nephropathy (IgAN) is a clinically and pathologically heterogeneous disease. Endocapillary proliferation is associated with higher risk of progressive disease, and clinical studies suggest that corticosteroids mitigate this risk. However, corticosteroids are associated with protean cellular effects and significant toxicity. Furthermore the precise mechanism by which they modulate kidney injury in IgAN is not well delineated. To better understand molecular pathways involved in the development of endocapillary proliferation and to identify novel specific therapeutic targets, we evaluated the glomerular transcriptome of microdissected kidney biopsies from 22 patients with IgAN. Endocapillary proliferation was defined according to the Oxford scoring system independently by 3 nephropathologists. We analyzed mRNA expression using microarrays and identified transcripts differentially expressed in patients with endocapillary proliferation compared to IgAN without endocapillary lesions. Next, we employed both transcription factor analysis and in silico drug screening and confirmed that the endocapillary proliferation transcriptome is significantly enriched with pathways that can be impacted by corticosteroids. With this approach we also identified novel therapeutic targets and bioactive small molecules that may be considered for therapeutic trials for the treatment of IgAN, including resveratrol and hydroquinine. In summary, we have defined the distinct molecular profile of a pathologic phenotype associated with progressive renal insufficiency in IgAN. Exploration of the pathways associated with endocapillary proliferation confirms a molecular basis for the clinical effectiveness of corticosteroids in this subgroup of IgAN, and elucidates new therapeutic strategies for IgAN. PMID- 25133639 TI - Believing is seeing: fixation duration predicts implicit negative attitudes. AB - A prototypical finding of social cognition is that social experiences influence later performance even though those experiences are not introspectively available. Building on social cognition research on implicit attitudes, we evaluate whether ethnic category/attribute pairs influence eye movements during the Implicit Association Test (IAT, Greenwald, McGhee, & Schwartz 1998). Results show that fixation duration predicted implicit attitudes such that when the category/attribute pairs disconfirmed one's implicit negative attitude fixation duration toward that pair increased. The present research provides evidence that eye movements and implicit processes inherent in the IAT are more broadly connected than previously thought. PMID- 25133640 TI - Association between perceived social stigma against mental disorders and use of health services for psychological distress symptoms in the older adult population: validity of the STIG scale. AB - OBJECTIVES: To document the reliability, construct and nomological validity of the perceived Social Stigmatisation (STIG) scale in the older adult population. DESIGN: Cross-sectional survey. SETTING: Primary medical health services clinics. PARTICIPANTS: Probabilistic sample of older adults aged 65 years and over waiting for medical services in the general medical sector (n = 1765). MEASUREMENTS: Perceived social stigma against people with a mental health problem was measured using the STIG scale composed of seven indicators. RESULTS: A second-order measurement model of perceived social stigma fitted adequately the observed data. The reliability of the STIG scale was 0.83. According to our results, 39.6% of older adults had a significant level of perceived social stigma against people with a mental health problem. RESULTS showed that the perception of social stigma against mental health problems was not significantly associated with a respondent gender and age. RESULTS also showed that the perception of social stigma against the mental health problems was directly associated with the respondents' need for improved mental health (b = -0.10) and indirectly associated with their use of primary medical health services for psychological distress symptoms (b = -0.07). CONCLUSION: RESULTS lead us to conclude that social stigma against mental disorders perceived by older adults may limit help-seeking behaviours and warrants greater public health and public policy attention. Also, results lead us to conclude that physicians should pay greater attention to their patients' attitudes against mental disorders in order to identify possible hidden mental health problems. PMID- 25133642 TI - The longitudinal impact of intimate partner aggression and relationship status on women's physical health and depression symptoms. AB - Intimate partner aggression (IPA) has many detrimental effects, particularly among young women. The present study examined the longitudinal effects of IPA victimization and relationship status on physical health and depression symptoms in a sample of 375 community women between the ages of 18 and 25 years. All variables were assessed at 4 occasions over a 12-month period (i.e., 1 assessment every 4 months). Multilevel modeling revealed that IPA victimization had both between- and within-person effects on women's health outcomes, and relationship status had within-person effects when women did not report current IPA. Although IPA was generally related to greater physical health problems and depression symptoms, these findings varied depending on both the type of aggression experienced (i.e., psychological vs. physical) and relationship status (i.e., whether participants were in the same relationship or a new relationship). Findings suggest that IPA can be harmful to both physical and mental health, particularly among young women who stay in abusive relationships. Results highlight the importance of developing effective IPA intervention programs and providing help and resources to women who are experiencing physical or psychological IPA in their relationships. PMID- 25133641 TI - The appropriateness of more intensive colonoscopy screening than recommended in Medicare beneficiaries: a modeling study. AB - IMPORTANCE: Many Medicare beneficiaries undergo more intensive colonoscopy screening than recommended. Whether this is favorable for beneficiaries and efficient from a societal perspective is uncertain. OBJECTIVE: To determine whether more intensive colonoscopy screening than recommended is favorable for Medicare beneficiaries (ie, whether it results in a net health benefit) and whether it is efficient from a societal perspective (ie, whether the net health benefit justifies the additional resources required). DESIGN, SETTING, AND PARTICIPANTS: Microsimulation modeling study of 65-year-old Medicare beneficiaries at average risk for colorectal cancer (CRC) and with an average life expectancy who underwent a screening colonoscopy at 55 years with negative results. INTERVENTIONS: Colonoscopy screening as recommended by guidelines (ie, at 65 and 75 years) vs scenarios with a shorter screening interval (5 or 3 instead of 10 years) or in which screening was continued to 85 or 95 years. MAIN OUTCOMES AND MEASURES: Quality-adjusted life-years (QALYs) gained (measure of net health benefit); additional colonoscopies required per additional QALY gained and additional costs per additional QALY gained (measures of efficiency). RESULTS: Screening previously screened Medicare beneficiaries more intensively than recommended resulted in only small increases in CRC deaths prevented and life years gained. In comparison, the increases in colonoscopies performed and colonoscopy-related complications experienced were large. As a result, all scenarios of more intensive screening than recommended resulted in a loss of QALYs, rather than a gain (ie, a net harm). The only exception was shortening the screening interval from 10 to 5 years, which resulted in 0.7 QALYs gained per 1000 beneficiaries. However, this scenario was inefficient because it required no less than 909 additional colonoscopies and an additional $711 000 per additional QALY gained. Results in previously unscreened beneficiaries were slightly less unfavorable, but conclusions were identical. CONCLUSIONS AND RELEVANCE: Screening Medicare beneficiaries more intensively than recommended is not only inefficient from a societal perspective; often it is also unfavorable for those being screened. This study provides evidence and a clear rationale for clinicians and policy makers to actively discourage this practice. PMID- 25133643 TI - Couples and breast cancer: women's mood and partners' marital satisfaction predicting support perception. AB - Women who are diagnosed with breast cancer can experience an array of psychosocial difficulties; however, social support, particularly from a spouse, has been shown to have a protective function during this time. This study examined the ways in which a woman's daily mood, pain, and fatigue, and her spouse's marital satisfaction predict the woman's report of partner support in the context of breast cancer. Pretest data from a larger intervention study and multilevel modeling were used to examine the effects of women's daily mood, pain, and fatigue and average levels of mood, pain, and fatigue on women's report of social support received from her partner, as well as how the effects of mood interacted with partners' marital satisfaction. Results show that on days in which women reported higher levels of negative or positive mood, as well as on days they reported more pain and fatigue, they reported receiving more support. Women who, on average, reported higher levels of positive mood tended to report receiving more support than those who, on average, reported lower positive mood. However, average levels of negative mood were not associated with support. Higher average levels of fatigue but not pain were associated with higher support. Finally, women whose husbands reported higher levels of marital satisfaction reported receiving more partner support, but husbands' marital satisfaction did not moderate the effect of women's mood on support. Implications of these findings are discussed relative to assisting couples during this difficult time in their lives. PMID- 25133644 TI - A randomized trial comparing time intervals from HCG trigger to intrauterine insemination for cycles utilizing GnRH antagonists. AB - Intrauterine insemination (IUI) during ovarian stimulation cycles is typically performed 36 hours after human chorionic gonadotropin (hCG) injection. We hypothesized that adjusting the time interval to IUI to better coincide with ovulation may increase pregnancy rates. Patients undergoing induction of ovulation utilizing gonadotropins and gonadotropin releasing hormone (GnRH) antagonists and IUI were divided to three groups based on the time from hCG injection to IUI: 36, 42, and 48 hours. Primary outcome was defined as the clinical pregnancy rate. Secondary outcomes comprised additional parameters including multifetal pregnancy rate. A total of 92 patients completed the study. Baseline parameters were similar between the groups. The clinical pregnancy rate in the three groups was 20%, 38%, and 24%, respectively. While the 42 hour time interval had a higher numerical pregnancy rate, the pregnancy rates did not differ statistically among the study groups. The multifetal pregnancy rate did not differ among the three groups as well. A larger study is necessary to ascertain if a 42 hour time interval can indeed improve pregnancy rates. PMID- 25133646 TI - Effect of frequent WBC treatments on the back pain therapy in elderly men. AB - Cryotherapy is the application of a stimulus of a cryotherapeutic temperature below -100 degrees C in a period of 1-3 min in order to stimulate and use physiological reactions of human body to cold. It can be applied to specific body parts or to a whole body. Whole-body cryotherapy is a treatment method applied in treatment of motor organ issues, nervous system diseases, psychiatry, dermatology and laryngology. The research group consisted of 80 male in the age range of 65 77 suffering from chronic, lasting more than 3 months, lower back pain. The subjects qualified to the research were divided into two groups. Group A consisted of 40 patients who participated in whole-body cryotherapy (WBC) twice a week. Group B also contained 40 patients who participated in WBC whole week. Examinations were conducted twice. The first one was conducted before the commencement of the treatment while the second one after the therapy was over. The results of the research did not show any statistically significant improvement in patients from Group A. However, the results obtained by Group B have proven significant condition improvement and enable the researchers to conclude that WBC is effective in treating patients with lower back pain. PMID- 25133645 TI - The Nijmegen decision tool for chronic low back pain. Development of a clinical decision tool for secondary or tertiary spine care specialists. AB - BACKGROUND: In Western Europe, low back pain has the greatest burden of all diseases. When back pain persists, different medical specialists are involved and a lack of consensus exists among these specialists for medical decision-making in Chronic Low Back Pain (CLBP). OBJECTIVE: To develop a decision tool for secondary or tertiary spine care specialists to decide which patients with CLBP should be seen by a spine surgeon or by other non-surgical medical specialists. METHODS: A Delphi study was performed to identify indicators predicting the outcome of interventions. In the preparatory stage evidence from international guidelines and literature were summarized. Eligible studies were reviews and longitudinal studies. Inclusion criteria: surgical or non-surgical interventions and persistence of complaints, CLBP-patients aged 18-65 years, reported baseline measures of predictive indicators, and one or more reported outcomes had to assess functional status, quality of life, pain intensity, employment status or a composite score. Subsequently, a three-round Delphi procedure, to reach consensus on candidate indicators, was performed among a multidisciplinary panel of 29 CLBP professionals (>five years CLBP-experience). The pre-set threshold for general agreement was >=70%. The final indicator set was used to develop a clinical decision tool. RESULTS: A draft list with 53 candidate indicators (38 with conclusive evidence and 15 with inconclusive evidence) was included for the Delphi study. Consensus was reached to include 47 indicators. A first version of the decision tool was developed, consisting of a web-based screening questionnaire and a provisional decision algorithm. CONCLUSIONS: This is the first clinical decision tool based on current scientific evidence and formal multidisciplinary consensus that helps referring the patient for consultation to a spine surgeon or a non-surgical spine care specialist. We expect that this tool considerably helps in clinical decision-making spine care, thereby improving efficient use of scarce sources and the outcomes of spinal interventions. PMID- 25133647 TI - Molecular features contributing to virus-independent intracellular localization and dynamic behavior of the herpesvirus transport protein US9. AB - Reaching the right destination is of vital importance for molecules, proteins, organelles, and cargoes. Thus, intracellular traffic is continuously controlled and regulated by several proteins taking part in the process. Viruses exploit this machinery, and viral proteins regulating intracellular transport have been identified as they represent valuable tools to understand and possibly direct molecules targeting and delivery. Deciphering the molecular features of viral proteins contributing to (or determining) this dynamic phenotype can eventually lead to a virus-independent approach to control cellular transport and delivery. From this virus-independent perspective we looked at US9, a virion component of Herpes Simplex Virus involved in anterograde transport of the virus inside neurons of the infected host. As the natural cargo of US9-related vesicles is the virus (or its parts), defining its autonomous, virus-independent role in vesicles transport represents a prerequisite to make US9 a valuable molecular tool to study and possibly direct cellular transport. To assess the extent of this autonomous role in vesicles transport, we analyzed US9 behavior in the absence of viral infection. Based on our studies, Us9 behavior appears similar in different cell types; however, as expected, the data we obtained in neurons best represent the virus-independent properties of US9. In these primary cells, transfected US9 mostly recapitulates the behavior of US9 expressed from the viral genome. Additionally, ablation of two major phosphorylation sites (i.e. Y32Y33 and S34ES36) have no effect on protein incorporation on vesicles and on its localization on both proximal and distal regions of the cells. These results support the idea that, while US9 post-translational modification may be important to regulate cargo loading and, consequently, virion export and delivery, no additional viral functions are required for US9 role in intracellular transport. PMID- 25133648 TI - Preparing for PrEP: perceptions and readiness of canadian physicians for the implementation of HIV pre-exposure prophylaxis. AB - Recent evidence has demonstrated the efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention, but concerns persist around its use. Little is known about Canadian physicians' knowledge of and willingness to prescribe PrEP. We disseminated an online survey to Canadian family, infectious disease, internal medicine, and public health physicians between September 2012-June 2013 to determine willingness to prescribe PrEP. Criteria for analysis were met by 86 surveys. 45.9% of participants felt "very familiar" with PrEP, 49.4% felt that PrEP should be approved by Health Canada, and 45.4% of respondents were willing to prescribe PrEP. Self-identifying as an HIV expert (odds ratio, OR = 4.1, 95% confidence interval, CI = 1.6-10.2), familiarity with PrEP (OR = 5.0, 95%CI = 1.3 19.0) and having been asked by patients about PrEP (OR = 4.0, 95%CI = 1.5-10.5) were positively associated with willingness to prescribe PrEP on univariable analysis. The latter two were the strongest predictors on multivariate analysis. Participants cited cost and efficacy as major concerns. 75.3% did not feel that information had been adequately disseminated among physicians. In summary, Canadian physicians demonstrate varying levels of support for PrEP and express concerns about its implementation. Further research on real-world effectiveness, continuing medical education, and clinical support is needed to prepare physicians for this prevention strategy. PMID- 25133649 TI - Potential therapeutic utility of mesenchymal stem cells in inflammatory bowel disease in mice. AB - Mesenchymal stem cells (MSCs) were found to provide an effective therapeutic role in inflammatory diseases by modulating inflammatory responses and tissue regeneration by their differentiation ability. The present work sought to demonstrate the potential therapeutic use of MSCs in treating chronic inflammatory bowel disease (IBD) in mice. A new model to induce chronic IBD based on alternative administration periods of Dextran Sodium Sulfate (DSS) was established. Mice were divided into 2 groups; one was treated with MSCs and the other was treated with phosphate-buffered saline (PBS). Assessment of therapeutic efficacy of MSCs was by measuring weight, stool scoring, histopathological examination, and measuring the gene expression of inflammatory markers: Interleukin-23 (IL-23), Tumor necrosis factor-alpha (TNF-alpha), Interferon-gamma (IFN-gamma), and Intercellular adhesion molecule-1 (ICAM-1). The results showed that DSS administration causes bloody and watery stool, weight loss, and altered histopathologic picture. MSC treated mice showed a significant improvement in stool condition, weight gain, and normal histopathologic picture compared to the PBS treated mice. Moreover, gene expressions of inflammatory markers in the intestines of the MSC treated mice were also significantly lower than those of the PBS treated mice. In conclusion, the data here showed that MSCs have a clear potential efficacy in the treatment for IBD, as their immune modulation effects include inhibition in the expression of key inflammatory markers that each plays an important role in the pathogenesis of IBD. PMID- 25133650 TI - Ketamine inhibits LPS-induced HGMB1 release in vitro and in vivo. AB - High mobility group box 1 (HMGB1) has been identified to be a critical mediator of severe sepsis. Ketamine has been shown to reduce sepsis-induced pathological complications. These effects are because of the reduced expression and release of several inflammatory mediators. However, whether ketamine affects the expression and release of HMGB1 is not known. We investigated the effect of ketamine on HMGB1 release in lipopolysaccharide (LPS)-induced macrophages in vitro and in cecal ligation and puncture (CLP)-induced septic rats in vivo, and determined its molecular mechanism of action. RAW264.7 cells or primary macrophages were incubated with or without LPS (500 ng/mL) in the presence or absence of ketamine, a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580), a nuclear factor-kappa B (NF-kappaB) inhibitor (pyrimidine dithiocarbamate), or small interfering RNA. The protein and expression levels of inflammatory mediators, such as HMGB1, tumor necrosis factor-alpha, and interleukin-1beta were measured using enzyme-linked immunosorbent assays and real-time polymerase chain reaction. The effect of ketamine on NF-kappaB and p38 MAPK activation was evaluated using enzyme-linked immunosorbent assays, Western blot analysis, and electrophoretic mobility shift assay. Western blotting was used to observe changes in translocation of HMGB1 from the nucleus to cytoplasm. In addition, CLP-induced septic rats were treated with ketamine (0.5, 5, 10 mg/kg) or saline (10 mL/kg) 3h after sepsis, and the levels of HMGB1 and functional parameters of multiple organs were determined using several detection kits. Seven-day survival was also assessed. Ketamine inhibited HMGB1 release in LPS-activated RAW264.7 cells and CLP-induced septic rats. Translocation of HMGB1 from the nucleus to cytosol and expression of HMGB1 mRNA were inhibited significantly by ketamine. Ketamine inhibited the translocation of NF-kappaB from the cytoplasm to the nucleus and phosphorylation of p38 MAPK in LPS-activated RAW264.7 cells. Rats treated with ketamine improved survival in rats and significantly reduced CLP-induced dysfunction/injury of organs. Ketamine suppresses LPS-induced HMGB1 release in LPS-activated RAW264.7 cells and a CLP-induced model of sepsis in rats by partially inhibiting NF-kappaB/p38 MAPK pathways. Ketamine increased survival time induced by CLP and reduced organ dysfunction in septic peritonitis. PMID- 25133651 TI - Walking for Transportation and Leisure Among U.S. Adults--National Health Interview Survey 2010. AB - BACKGROUND: Walking, the most commonly reported physical activity among U.S. adults, is undertaken in various domains, including transportation and leisure. METHODS: This study examined prevalence, bout length, and mean amount of walking in the last week for transportation and leisure, by selected characteristics. Self-reported data from the 2010 National Health Interview Survey (N = 24,017) were analyzed. RESULTS: Prevalence of transportation walking was 29.4% (95% CI: 28.6%-30.3%) and of leisure walking was 50.0% (95% CI: 49.1%-51.0%). Prevalence of transportation walking was higher among men; prevalence of leisure walking was higher among women. Most (52.4%) transportation walking bouts were 10 to 15 minutes; leisure walking bouts were distributed more evenly (28.0%, 10-15 minutes; 17.1%, 41-60 minutes). Mean time spent in transportation walking was higher among men, decreased with increasing BMI, and varied by race/ethnicity and region of residence. Mean time spent leisure walking increased with increasing age and with decreasing BMI. CONCLUSION: Demographic correlates and patterns of walking differ by domain. Interventions focusing on either leisure or transportation walking should consider correlates for the specific walking domain. Assessing prevalence, bout length, and mean time of walking for transportation and leisure separately allows for more comprehensive surveillance of walking. PMID- 25133652 TI - Phase separation of aqueous poly(2-dimethylaminoethyl methacrylate-block-N vinylcaprolactams). AB - Details of the phase separation of the poly(N-vinylcaprolactam) (PVCL) homopolymers and block copolymers of PVCL and poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) were studied in aqueous buffer solutions. Phase separation occurred at either one or two temperatures depending on pH. The lower critical solution temperature of PVCL can be fine-tuned by varying the molecular weight of the block, whereas the phase separation temperature of the PDMAEMA block is strongly dependent on pH. The enthalpies of the collapse of the PVCL homopolymer and PVCL-b-PDMAEMA block copolymers were measured and show that the blocks phase separate independently upon heating. PVCL is known to bind amphiphilic cations, and correspondingly, according to light scattering, the block copolymers dissolve as single molecules but also form aggregates at room temperature. At temperatures above the cloud points of both blocks, only homogeneous large aggregates were observed. Zeta potential measurements confirmed that, upon heating, PDMAEMA blocks turn out from the collapsed PVCL globule toward the aqueous phase. PMID- 25133653 TI - Acid-reducing agents in infants and children: friend or foe? PMID- 25133656 TI - Comparative analysis of risky behaviors of electric bicycles at signalized intersections. AB - OBJECTIVE: The primary objective of this study was to compare the risky behaviors of e-bike, e-scooter, and bicycle riders as they were crossing signalized intersections. METHODS: Pearson's chi-square test was used to identify whether there were significant differences in the risky behaviors among e-bike, e scooter, and bicycle riders. Binary logit models were developed to evaluate how various variables affected the behaviors of 2-wheeled vehicle riders at signalized intersections. Field data collection was conducted at 13 signalized intersections in 2 cities (Nanjing and Kunming) in China. RESULTS: Three different types of risky behaviors were identified, including stop beyond the stop line, riding in motorized lanes, and riding against traffic. Two-wheeled vehicle riders' gender and age and traffic conditions were significantly associated with the behaviors of 2-wheeled vehicle riders at the selected signalized intersections. CONCLUSIONS: Compared to e-bike and bicycle riders, e scooter riders are more likely to take risky behaviors. More specifically, they are more likely to ride in motorized lanes and ride against traffic. PMID- 25133655 TI - PEGylation of concanavalin A to improve its stability for an in vivo glucose sensing assay. AB - Competitive binding assays utilizing concanavalin A (ConA) have the potential to be the basis of improved continuous glucose monitoring devices. However, the efficacy and lifetime of these assays have been limited, in part, by ConA's instability due to its thermal denaturation in the physiological environment (37 degrees C, pH 7.4, 0.15 M NaCl) and its electrostatic interaction with charged molecules or surfaces. These undesirable interactions change the constitution of the assay and the kinetics of its behavior over time, resulting in an unstable glucose response. In this work, poly(ethylene glycol) (PEG) chains are covalently attached to lysine groups on the surface of ConA (i.e., PEGylation) in an attempt to improve its stability in these environments. Dynamic light scattering measurements indicate that PEGylation significantly improved ConA's thermal stability at 37 degrees C, remaining stable for at least 30 days. Furthermore, after PEGylation, ConA's binding affinity to the fluorescent competing ligand previously designed for the assay was not significantly affected and remained at ~5.4 * 10(6) M(-1) even after incubation at 37 degrees C for 30 days. Moreover, PEGylated ConA maintained the ability to track glucose concentrations when implemented within a competitive binding assay system. Finally, PEGylation showed a reduction in electrostatic-induced aggregation of ConA with poly(allylamine), a positively charged polymer, by shielding ConA's charges. These results indicate that PEGylated ConA can overcome the instability issues from thermal denaturation and nonspecific electrostatic binding while maintaining the required sugar binding characteristics. Therefore, the PEGylation of ConA can overcome major hurdles for ConA-based glucose sensing assays to be used for long-term continuous monitoring applications in vivo. PMID- 25133657 TI - Long-term sustainable aluminum precursor solution for highly conductive thin films on rigid and flexible substrates. AB - To fabricate the highly conductive Al film via a solution process, AlH3 etherates have been a unique Al source despite their chemical instability in solvents and thus lack of long-term sustainability. Herein, we suggest an innovative solution process to overcome the aforementioned drawbacks in AlH3 etherates; AlH3 aminates powder, which can be stored in low temperature surroundings and redissolved in solvents whenever it is needed. Since refrigeration of AlH3 aminates, AlH3{N(CH3)3}, was very effective to prevent its chemical degradation, Al film with excellence and uniformity in electrical and mechanical properties was successfully fabricated even by the 180-day stored AlH3{N(CH3)3} dissolved in solvents. Moreover, the applicability of long-term stored AlH3{N(CH3)3} to electronic devices was experimentally demonstrated by the successful operation of LED lamps connected to the Al pattern films on glass, PET, and paper substrates. PMID- 25133658 TI - Accessing 2,1-borazaronaphthols: self-arylation of 1-alkyl-2-aryl-3-bromo-2,1 borazaronaphthalenes. AB - Unlike their B-alkyl counterparts, brominated N-alkyl B-aryl 2,1 borazaronaphthalenes undergo a self-arylation reaction in the presence of a catalytic amount of palladium and base, in which the azaborine serves as both the electrophile and the nucleophile. The products of the self-arylation are air- and moisture-stable 2,1-borazaronaphthols, previously only observed in basic alcoholic solvents. The steric encumbrance of the azaborine appears to prevent formation of the corresponding boron acid anhydride, allowing access to a family of 2,1-borazaronaphthol derivatives. PMID- 25133660 TI - Cancer screening in older persons: a new age of wonder. PMID- 25133659 TI - Peer victimization and peer rejection during early childhood. AB - The development and course of the subtypes of peer victimization is a relatively understudied topic despite the association of victimization with important developmental and clinical outcomes. Moreover, understanding potential predictors, such as peer rejection and emotion regulation, in early childhood may be especially important to elucidate possible bidirectional pathways between relational and physical victimization and rejection. The current study (N = 97) was designed to explore several gaps and limitations in the peer victimization and peer rejection literature. In particular, the prospective associations between relational and physical victimization and peer rejection over the course of 3.5 months during early childhood (i.e., 3 to 5 years old) were investigated in an integrated model. The study consisted of 97 (42 girls) preschool children recruited from four early childhood schools in the northeast of the United States. Using observations, research assistant report, and teacher report, relational and physical aggression, relational and physical victimization, peer rejection, and emotion regulation were measured in a short-term longitudinal study. Path analyses were conducted to test the overall hypothesized model. Peer rejection was found to predict increases in relational victimization. In addition, emotion regulation was found to predict decreases in peer rejection and physical victimization. Implications for research and practice are discussed, including teaching coping strategies for peer rejection and emotional distress. PMID- 25133661 TI - Increasing external effects negate local efforts to control ozone air pollution: a case study of Hong Kong and implications for other Chinese cities. AB - It is challenging to reduce ground-level ozone (O3) pollution at a given locale, due in part to the contributions of both local and distant sources. We present direct evidence that the increasing regional effects have negated local control efforts for O3 pollution in Hong Kong over the past decade, by analyzing the daily maximum 8 h average O3 and Ox (=O3+NO2) concentrations observed during the high O3 season (September-November) at Air Quality Monitoring Stations. The locally produced Ox showed a statistically significant decreasing trend over 2002 2013 in Hong Kong. Analysis by an observation-based model confirms this decline in in situ Ox production, which is attributable to a reduction in aromatic hydrocarbons. However, the regional background Ox transported into Hong Kong has increased more significantly during the same period, reflecting contributions from southern/eastern China. The combined result is a rise in O3 and a nondecrease in Ox. This study highlights the urgent need for close cross-boundary cooperation to mitigate the O3 problem in Hong Kong. China's air pollution control policy applies primarily to its large cities, with little attention to developing areas elsewhere. The experience of Hong Kong suggests that this control policy does not effectively address secondary pollution, and that a coordinated multiregional program is required. PMID- 25133663 TI - The incorporation of low-substituted hydroxypropyl cellulose into solid dispersion systems. AB - While the use of amorphous solid dispersions to improve aqueous solubility is well documented, little consideration has traditionally been given to the finished dosage form. The objective of this study was to evaluate the dissolution performance of amorphous solid dispersions containing a dispersed superdisintegrant with binding properties. KinetiSol(r) dispersing was used to thermally process hypromellose acetate succinate-based compositions containing the drug substance nifedipine (NIF) and a highly compressible grade of low substituted hydroxypropyl cellulose (New Binder Disintegrants; NBD-grade). Solid state analysis demonstrated that compositions were rendered amorphous during processing. Tablets containing intra-dispersion NBD were found to exhibit non sink dissolution performance similar to milled intermediate, demonstrating excellent disintegration characteristics. Conversely, tablets without intra dispersion NBD were found to release significantly less NIF during dissolution analysis due to particle agglomeration. It was determined that compressibility and particle wetting increased as the level of intra-dispersion NBD increased. PMID- 25133662 TI - The effects of obesity and mobility disability in access to breast and cervical cancer screening in france: results from the national health and disability survey. AB - OBJECTIVES: We aimed to disentangle the effects of obesity and mobility limitation on cervical and breast cancer screening among community dwelling women. METHODS: The data source was the French national Health and Disability Survey - Household Section, 2008. The Body Mass Index (BMI) was used to categorize obesity status. We constructed a continuous score of mobility limitations to assess the severity of disability (Cronbach's alpha = 0.84). Logistic regressions were performed to examine the association between obesity, mobility limitations and the use of Pap test (n = 8 133) and the use of mammography (n = 7 561). Adjusted odds ratios were calculated (AOR). Interaction terms between obesity and the disability score were included in models testing for effect modifications. RESULTS: Compared with non-obese women, the odds of having a Pap test in the past 3 years was 24% lower in obese women (AOR = 0.76; 95% CI: 0.65 to 0.89), the odds of having a mammogram in the past 2 years was 23% lower (AOR = 0.77; 95% CI: 0.66 to 0.91). Each time the disability score was 5 points higher, the odds of having a Pap test decreases by 20% (AOR = 0.96; 95% CI: 0.94 to 0.98), the odds of having a mammogram decreases by 25% (AOR = 0.95; 95% CI: 0.94 to 0.97). There was no significant interaction between obesity and disability score. CONCLUSION: Obesity and mobility limitation are independently associated with a lower likelihood of cervical and breast cancer screening. Protective outreach and follow-up are necessary to reduce inequalities and thus to reduce health disparities in these vulnerable and high-risk populations of obese women with disabilities. PMID- 25133664 TI - Increased dissolution of disulfiram by dry milling with silica nanoparticles. AB - The purpose of this study was to find a suitable method to increase the dissolution of disulfiram (DSF) which is easily decomposed. The dissolution of DSF within 1 h was significantly increased from 37% to >90% by co-milling with Aerosil(r) 200 pharm (Aerosil) and the increased dissolution remained stable during long-term storage while there was no significant degradation of DSF. By monitoring the changes in particle size of the grinding mixture, a mosaic DSF-in Aerosil structure was demonstrated. The core size of the mosaic DSF/Aerosil system was 3.625 um. The particle size of DSF was reduced from 20.75 um to ~200 nm and the size of the mosaic DSF/Aerosil system (3.625~7.956 um) increased on increasing the drug-loading content. Differential scanning calorimetry and X-ray powder diffraction analysis confirmed the largely amorphous state of DSF in the mosaic drug/carrier system. Fourier transform infrared spectroscopy confirmed the presence of hydrogen bonding between DSF and Aerosil. Scanning electron microscopy and transmission electron microscopy verified the DSF-in-Aerosil relationship in the particle size determination at different size levels. The possible mechanisms of dry milling included the hypothesis that during impact and collision, DSF particles melted into the surface of Aerosil turning them into an amorphous state or they became inlayed into the interspaces of the Aerosil structure with a much smaller size. PMID- 25133666 TI - Maternal and umbilical cord copeptin levels in pregnancies complicated by fetal growth restriction. AB - Abstract Objective: The aim of this study was to compare maternal and fetal serum copeptin concentrations in pregnancies complicated by isolated fetal growth restriction (FGR), and uncomplicated pregnancies, and to investigate relationships between copeptin levels and clinical parameters. Methods: Maternal and fetal serum copeptin levels were measured in 21 women with pregnancies complicated by isolated FGR and 20 women with normal pregnancies (control group). Doppler assessment of the uterine and umbilical arteries was performed in each patient. Results: Maternal serum copeptin levels were significantly higher in women with isolated FGR compared to controls (p = 0.042). In addition, maternal copeptin levels were inversely correlated with the uterine artery pulsatility and resistance indices and positively correlated with neonatal birth weight. Umbilical vein copeptin levels were significantly increased in neonates with adverse outcomes (p = 0.001). Conclusions: Increased maternal copeptin concentration may reflect a response to stress, thus serving as a compensatory mechanism in pregnancies complicated by FGR. PMID- 25133667 TI - Ruthenium-catalyzed allylic alkylations of chelated enolates using vinyl dioxolanon-2-ones. AB - 4-Vinyl-substituted 1,3-dioxolan-2-ones are found to be good substrates for Ru catalyzed allylic alkylations of chelated amino acid ester enolates. cis-1,3 Dioxolan-2-ones are more reactive than the corresponding trans-isomers. The attack occurs preferentially with regioretention at the position of the leaving group with perfect chirality transfer. Therefore, this protocol is a good complement to the Pd-catalyzed processes, which give only linear products with this type of substrate. PMID- 25133665 TI - Abnormal amygdala resting-state functional connectivity in adolescent depression. AB - IMPORTANCE: Major depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships. OBJECTIVE: To examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional resting state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses. MAIN OUTCOMES AND MEASURES: Using a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level dependent signal of each voxel in the whole brain with that of the amygdala. RESULTS: Adolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R = -.523, P = .01), dysphoria (R = -.455, P = .05), and lassitude (R = -.449, P = .05) and was positively correlated with well-being (R = .470, P = .03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls. CONCLUSIONS AND RELEVANCE: Impaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression. PMID- 25133668 TI - p53-Dependent apoptosis induced in human bronchial epithelial (16-HBE) cells by PM(2.5) sampled from air in Guangzhou, China. AB - Epidemiological studies have shown that air pollution particulate matter (PM) is associated with increased respiratory morbidity and mortality. However, the mechanisms are not fully understood. Oxidative stress-mediated apoptosis plays an important role in the occurrence of respiratory diseases. In this study, human bronchial epithelial (16-HBE) cells were exposed to different concentrations (16 128 ug/ml) of PM(2.5) for 24 h to investigate the apoptosis induced by PM(2.5). The results showed that PM(2.5) exposure significantly induced apoptosis, DNA strand breaks, and oxidative damage in a dose-dependent manner in 16-HBE cells. The expression of p53 and p73 increased significantly along with the dose of PM(2.5) in 16-HBE cells, whereas the expression of p21(Cip1/WAF1) decreased; the expression of mdm2 increased and then decreased, but not significantly. Taken together, these observations indicate that PM(2.5) may lead to oxidative damage and induce apoptosis through the p53-dependent pathway in 16-HBE cells. p53 Dependent apoptosis mediated by DNA strand breaks may be an important mechanism of PM(2.5)-induced apoptosis in 16-HBE cells. PMID- 25133669 TI - Coinfection with human herpesvirus 8 is associated with persistent inflammation and immune activation in virologically suppressed HIV-infected patients. AB - OBJECTIVES: Infection with co-pathogens is one of the postulated factors contributing to persistent inflammation and non-AIDS events in virologically suppressed HIV-infected patients. We aimed to investigate the relationship of human herpesvirus-8 (HHV-8), a vasculotropic virus implicated in the pathogenesis of Kaposi's sarcoma, with inflammation and subclinical atherosclerosis in HIV infected patients. METHODS: Prospective study including virologically suppressed HIV-infected patients. Several blood biomarkers (highly-sensitive C-reactive protein [hsCRP], tumour necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, malondialdehyde, plasminogen activator inhibitor [PAI-1], D dimer, sCD14, sCD163, CD4/CD38/HLA-DR, and CD8/CD38/HLA-DR), serological tests for HHV-8 and the majority of herpesviruses, carotid intima-media thickness, and endothelial function through flow-mediated dilatation of the brachial artery were measured. RESULTS: A total of 136 patients were included, 34.6% of them infected with HHV-8. HHV-8-infected patients were more frequently co-infected with herpes simplex virus type 2 (HSV-2) (P<0.001), and less frequently with hepatitis C virus (HCV) (P = 0.045), and tended to be older (P = 0.086). HHV-8-infected patients had higher levels of hsCRP (median [interquartile range], 3.63 [1.32 7.54] vs. 2.08 [0.89-4.11] mg/L, P = 0.009), CD4/CD38/HLA-DR (7.67% [4.10-11.86]% vs. 3.86% [2.51-7.42]%, P = 0.035) and CD8/CD38/HLA-DR (8.02% [4.98-14.09]% vs. 5.02% [3.66-6.96]%, P = 0.018). After adjustment for the traditional cardiovascular risk factors, HCV and HSV-2 infection, the associations remained significant: adjusted difference between HHV-8 positive and negative patients (95% confidence interval) for hsCRP, 74.19% (16.65-160.13)%; for CD4/CD38/HLA-DR, 89.65% (14.34-214.87)%; and for CD8/CD38/HLA-DR, 58.41% (12.30-123.22)%. Flow mediated dilatation and total carotid intima-media thickness were not different according to HHV-8 serostatus. CONCLUSION: In virologically suppressed HIV infected patients, coinfection with HHV-8 is associated with increased inflammation and immune activation. This might contribute to increase the risk of non-AIDS events, including accelerated atherosclerotic disease. PMID- 25133670 TI - The impact of visual impairment on health-related quality of life in rural Africa. AB - PURPOSE: To assess the impact of visual impairment (VI) on utility values in Sub Saharan Africa and compare findings with other studies from low- and high-income countries. METHODS: Patients with normal vision and various levels of VI were recruited from a secondary eye clinic in rural Kenya and interviewed using time trade-off (TTO). VI was classified using the World Health Organization definition of (normal vision, visual acuity >=20/60, VI 20/80-20/200, severe VI 20/240 20/400, and blindness <20/400). RESULTS: Mean age of the total sample (N = 303) was 50.3 years (standard deviation, SD, +/-18.17 years), and 51.5% of patients were male. Most were small-scale farmers and illiteracy was high at 40%. Mean TTO scores per group were: normal vision 0.93 (SD +/- 0.10), VI 0.88 (SD +/- 0.14), severe VI 0.86 (SD +/- 0.13), blindness 0.73 (SD +/- 0.17; p <= 0.001). Lower TTO scores were independently associated with worse visual acuity (p <= 0.001), longer duration of disease (p <= 0.001) and illiteracy (p = 0.011), but not with cause of VI, age, sex, marital status, socioeconomic status, or systemic comorbidities in multivariate analyses. Overall, TTO scores were considerably higher than those reported from high-income countries at similar levels of VI. CONCLUSION: In this rural African population, duration and extent of vision loss, rather than cause, socioeconomic factors and comorbidities affected vision related quality of life. Our findings underline the importance of providing sight restoring treatment as timely as possible and the necessity of enhancing rehabilitation efforts for those with non-curable eye diseases. PMID- 25133671 TI - Hemoglobin is associated with retinal vascular fractals in type 1 diabetes patients. AB - PURPOSE: Retinal vascular fractal dimension, a measure of the density of the retinal vasculature, has been suggested as a marker of systemic microvascular disorders in diabetes. As hemoglobin concentration is tightly related to vascular physiology and hypoxia, the hypothesis was that hemoglobin concentration would be associated with retinal vascular fractals in a relevant population. METHODS: In a cross-sectional study of 204 long-term type 1 diabetes patients from a population based cohort, retinal digital photos were captured and graded for fractal dimension (Df) by International Retinal Imaging Software - Fractal (IRIS Fractal). Df was calculated from a disc-centered retinal photo from the right eye. Hemoglobin concentrations were measured using routine equipment. RESULTS: Of 175 patients with gradable images, median age was 57.7 years and median duration of diabetes was 42 years. Median retinal Df was 1.4606 (inter-quartile range 0.0264). A positive correlation was found between hemoglobin concentration and retinal vascular Df (r = 0.23, p = 0.0018). In a multiple linear regression model, Df was associated with hemoglobin (coefficient 0.0054 per 1.0 mmol/L increase in hemoglobin, p = 0.01) and age (coefficient -0.0046 for each 10-year increase in age, p = 0.04). CONCLUSION: Hemoglobin correlated independently with retinal vascular fractals indicating a relationship between hemoglobin availability and retinal vascular structure. PMID- 25133672 TI - Modifying effect of a common polymorphism in the interleukin-6 promoter on the relationship between long-term exposure to traffic-related particulate matter and heart rate variability. AB - BACKGROUND: Exposure to particulate matter (PM) has been associated with an increase in many inflammatory markers, including interleukin 6 (IL6). Air pollution exposure has also been suggested to induce an imbalance in the autonomic nervous system (ANS), such as a decrease in heart rate variability (HRV). In this study we aimed to investigate the modifying effect of polymorphisms in a major proinflammatory marker gene, interleukin 6 (IL6), on the relationship between long-term exposure to traffic-related PM10 (TPM10) and HRV. METHODS: For this cross-sectional study we analysed 1552 participants of the SAPALDIA cohort aged 50 years and older. Included were persons with valid genotype data, who underwent ambulatory 24-hr electrocardiogram monitoring, and reported on medical history and lifestyle. Main effects of annual average TPM10 and IL6 gene variants (rs1800795; rs2069827; rs2069840; rs10242595) on HRV indices and their interaction with average annual exposure to TPM10 were tested, applying a multivariable mixed linear model. RESULTS: No overall association of TPM10 on HRV was found. Carriers of two proinflammatory G-alleles of the functional IL6 -174 G/C (rs1800795) polymorphism exhibited lower HRV. An inverse association between a 1 ug/m3 increment in yearly averaged TPM10 and HRV was restricted to GG genotypes at this locus with a standard deviation of normal-to normal intervals (SDNN) (GG-carriers: -1.8%; 95% confidence interval -3.5 to 0.01; pinteraction(additive) = 0.028); and low frequency power (LF) (GG-carriers: -5.7%; 95%CI: -10.4 to -0.8; pinteraction(dominant) = 0.049). CONCLUSIONS: Our results are consistent with the hypothesis that traffic-related air pollution decreases heart rate variability through inflammatory mechanisms. PMID- 25133673 TI - Tumor bioengineering using a transglutaminase crosslinked hydrogel. AB - Development of a physiologically relevant 3D model system for cancer research and drug development is a current challenge. We have adopted a 3D culture system based on a transglutaminase-crosslinked gelatin gel (Col-Tgel) to mimic the tumor 3D microenvironment. The system has several unique advantages over other alternatives including presenting cell-matrix interaction sites from collagen derived peptides, geometry-initiated multicellular tumor spheroids, and metabolic gradients in the tumor microenvironment. Also it provides a controllable wide spectrum of gel stiffness for mechanical signals, and technical compatibility with imaging based screening due to its transparent properties. In addition, the Col-Tgel provides a cure-in-situ delivery vehicle for tumor xenograft formation in animals enhancing tumor cell uptake rate. Overall, this distinctive 3D system could offer a platform to more accurately mimic in vivo situations to study tumor formation and progression both in vitro and in vivo. PMID- 25133675 TI - Palladium-catalyzed amination of aryl chlorides and bromides with ammonium salts. AB - We report the palladium-catalyzed coupling of aryl halides with ammonia and gaseous amines as their ammonium salts. The coupling of aryl chlorides and ortho substituted aryl bromides with ammonium sulfate forms anilines with higher selectivity for the primary arylamine over the diarylamine than couplings with ammonia in dioxane. The resting state for the reactions of aryl chlorides is different from the resting state for the reactions of aryl bromides, and this change in resting states is proposed to account for a difference in selectivities for reactions of the two haloarenes. PMID- 25133677 TI - Lithium potential variations for metastable materials: case study of nanocrystalline and amorphous LiFePO4. AB - Much attention has been paid to metastable materials in the lithium battery field, especially to nanocrystalline and amorphous materials. Nonetheless, fundamental issues such as lithium potential variations have not been pertinently addressed. Using LiFePO4 as a model system, we inspect such lithium potential variations for various lithium storage modes and evaluate them thermodynamically. The conclusions of this work are essential for an adequate understanding of the behavior of electrode materials and even helpful in the search for new energy materials. PMID- 25133674 TI - A quantitative proteomic approach to identify significantly altered protein networks in the serum of patients with lymphangioleiomyomatosis (LAM). AB - Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung condition affecting approximately 3.4-7.5/million women, with an average lag time between symptom onset and diagnosis of upwards of 4 years. The aim of this work was to identify altered proteins in LAM serum which may be potential biomarkers of disease. Serum from LAM patient volunteers and healthy control volunteers were pooled and analysis carried out using quantitative 4-plex iTRAQ technology. Differentially expressed proteins were validated using ELISAs and pathway analysis was carried out using Ingenuity Pathway Analysis. Fourteen proteins were differentially expressed in LAM serum compared to control serum (p<0.05). Further screening validated the observed differences in extracellular matrix remodelling proteins including fibronectin (30% decrease in LAM, p = 0.03), von Willebrand Factor (40% reduction in LAM, p = 0.03) and Kallikrein III (25% increase in LAM, p = 0.03). Pathway networks elucidated the relationships between the ECM and cell trafficking in LAM. This study was the first to highlight an imbalance in networks important for remodelling in LAM, providing a set of novel potential biomarkers. These understandings may lead to a new effective treatment for LAM in the future. PMID- 25133676 TI - Capacity choice in a large market. AB - We analyze endogenous capacity formation in a large frictional market with perfectly divisible goods. Each seller posts a price and decides on a capacity. The buyers base their decision on which seller to visit on both characteristics. In this setting we determine the conditions for the existence and uniqueness of a symmetric equilibrium. When capacity is unobservable there exists a continuum of equilibria. We show that the "best" of these equilibria leads to the same seller capacities and the same number of trades as the symmetric equilibrium under observable capacity. PMID- 25133678 TI - Phosphorus complexes of meso-triaryl-25-oxasmaragdyrins. AB - The aromatic PO2 complexes of meso-triaryl-25-oxasmaragdyrins were synthesized by treating the free base 25-oxasmaragdyrins with POCl3 in toluene/triethylamine at refluxing temperature. The complexes are stable and characterized by X-ray and different spectroscopic techniques. In these complexes, the phosphorus(V) ion was bound to two pyrrolic nitrogen atoms of the smaragdyrin macrocycle and two oxygen atoms in tetrahedral geometry. The X-ray structure revealed that the smaragdyrin macrocycle showed significant distortion upon insertion of a PO2 unit, and the phosphorus atom lies 1.339 A above the mean plane defined by three meso-carbon atoms of the macrocycle. These complexes absorb strongly in the visible region and are 2.5 times more strongly fluorescent than free base 25-oxasmaragdyrins. The smaragdyrin macrocycle becomes electron-deficient upon complexation with a PO2 unit because these complexes are easier to reduce but difficult to oxidize compared to free base smaragdyrins. We designed and synthesized a covalently linked BODIPY-PO2-smaragdyrin dyad and demonstrated efficient energy transfer from the BODIPY unit to the PO2-smaragdyrin unit. PMID- 25133680 TI - Oleic acid phase behavior from molecular dynamics simulations. AB - Fatty acid aggregation is important for a number of diverse applications: from origins of life research to industrial applications to health and disease. Experiments have characterized the phase behavior of oleic acid mixtures, but the molecular details are complex and hard to probe with many experiments. Coarse grained molecular dynamics computer simulations and free energy calculations are used to model oleic acid aggregation. From random dispersions, we observe the aggregation of oleic acid monomers into micelles, vesicles, and oil phases, depending on the protonation state of the oleic acid head groups. Worm-like micelles are observed when all the oleic acid molecules are deprotonated and negatively charged. Vesicles form spontaneously if significant amounts of both neutral and negative oleic acid are present. Oil phases form when all the fatty acids are protonated and neutral. This behavior qualitatively matches experimental observations of oleic acid aggregation. To explain the observed phase behavior, we use umbrella sampling free energy calculations to determine the stability of individual monomers in aggregates compared to water. We find that both neutral and negative oleic acid molecules prefer larger aggregates, but neutral monomers prefer negatively charged aggregates and negative monomers prefer neutral aggregates. Both neutral and negative monomers are most stable in a DOPC bilayer, with implications on fatty acid adsorption and cellular membrane evolution. Although the CG model qualitatively reproduces oleic acid phase behavior, we show that an updated polarizable water model is needed to more accurately predict the shift in pKa for oleic acid in model bilayers. PMID- 25133682 TI - Passport officers' errors in face matching. AB - Photo-ID is widely used in security settings, despite research showing that viewers find it very difficult to match unfamiliar faces. Here we test participants with specialist experience and training in the task: passport issuing officers. First, we ask officers to compare photos to live ID-card bearers, and observe high error rates, including 14% false acceptance of 'fraudulent' photos. Second, we compare passport officers with a set of student participants, and find equally poor levels of accuracy in both groups. Finally, we observe that passport officers show no performance advantage over the general population on a standardised face-matching task. Across all tasks, we observe very large individual differences: while average performance of passport staff was poor, some officers performed very accurately--though this was not related to length of experience or training. We propose that improvements in security could be made by emphasising personnel selection. PMID- 25133683 TI - Lipid structure in triolein lipid droplets. AB - Lipid droplets (LDs) are primary repositories of esterified fatty acids and sterols in animal cells. These organelles originate on the lumenal or cytoplasmic side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In contrast to other intracellular organelles, LDs are composed of a mass of hydrophobic lipid esters coved by phospholipid monolayer. The small size and unique architecture of LDs makes it complicated to study LD structure by modern experimental methods. We discuss coarse-grained molecular dynamics (MD) simulations of LD formation in systems containing 1-palmitoyl-2-oleoyl-sn-glycero 3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), triolein (TO), cholesterol (CHOL), and water. We find that (1) there is more cholesterol in the LD core, than at the interface. (2) No crystallization occurs inside the LD core. (3) According to coarse-grained simulations, the presence of PE lipids at the interface has a little impact on distribution of components and on the overall LD structure. (4) The thickness of the lipid monolayer at the surface of the droplet is similar to the thickness of one leaflet of a bilayer. Computer simulations are shown to be a mighty tool to provide molecular-level insights, which are not available to the experimental techniques. PMID- 25133679 TI - Activated CD8+ T lymphocytes inhibit neural stem/progenitor cell proliferation: role of interferon-gamma. AB - The ability of neural stem/progenitor cells (NSCs) to self-renew, migrate to damaged sites, and differentiate into neurons has renewed interest in using them in therapies for neurodegenerative disorders. Neurological diseases, including viral infections of the brain, are often accompanied by chronic inflammation, whose impact on NSC function remains unexplored. We have previously shown that chronic neuroinflammation, a hallmark of experimental herpes simplex encephalitis (HSE) in mice, is dominated by brain-infiltrating activated CD8 T-cells. In the present study, activated CD8 lymphocytes were found to suppress NSC proliferation profoundly. Luciferase positive (luc+) NSCs co-cultured with activated, MHC matched, CD8+ lymphocytes (luc-) showed two- to five-fold lower luminescence than co-cultures with un-stimulated lymphocytes. On the other hand, similarly activated CD4+ lymphocytes did not suppress NSC growth. This differential lymphocyte effect on proliferation was confirmed by decreased BrdU uptake by NSC cultured with activated CD8 T-cells. Interestingly, neutralizing antibodies to interferon-gamma (IFN-gamma) reversed the impact of CD8 lymphocytes on NSCs. Antibodies specific to the IFN-gamma receptor-1 subunit complex abrogated the inhibitory effects of both CD8 lymphocytes and IFN-gamma, indicating that the inhibitory effect of these cells was mediated by IFN-gamma in a receptor-specific manner. In addition, activated CD8 lymphocytes decreased levels of nestin and Sox2 expression in NSCs while increasing GFAP expression, suggesting possible induction of an altered differentiation state. Furthermore, NSCs obtained from IFN-gamma receptor-1 knock-out embryos were refractory to the inhibitory effects of activated CD8+ T lymphocytes on cell proliferation and Sox2 expression. Taken together, the studies presented here demonstrate a role for activated CD8 T-cells in regulating NSC function mediated through the production of IFN-gamma. This cytokine may influence neuro-restorative processes and ultimately contribute to the long-term sequelae commonly seen following herpes encephalitis. PMID- 25133684 TI - Three-dimensional flash flow microreactor for scale-up production of monodisperse PEG-PLGA nanoparticles. AB - We present a pressure-tolerant 3D parallel polyimide (PI) film microreactor operating at up to ~160 bars with direct 3D flow focusing geometry for mass production of PEG-PLGA nanoparticles in a ~10(1) gram-scale (g h(-1)). PMID- 25133685 TI - Relationship between phylogeny and immunity suggests older Caribbean coral lineages are more resistant to disease. AB - Diseases affect coral species fitness and contribute significantly to the deterioration of coral reefs. The increase in frequency and severity of disease outbreaks has made evaluating and determining coral resistance a priority. Phylogenetic patterns in immunity and disease can provide important insight to how corals may respond to current and future environmental and/or biologically induced diseases. The purpose of this study was to determine if immunity, number of diseases and disease prevalence show a phylogenetic signal among Caribbean corals. We characterized the constitutive levels of six distinct innate immune traits in 14 Caribbean coral species and tested for the presence of a phylogenetic signal on each trait. Results indicate that constitutive levels of some individual immune related processes (i.e. melanin concentration, peroxidase and inhibition of bacterial growth), as well as their combination show a phylogenetic signal. Additionally, both the number of diseases affecting each species and disease prevalence (as measures of disease burden) show a significant phylogenetic signal. The phylogenetic signal of immune related processes, combined with estimates of species divergence times, indicates that among the studied species, those belonging to older lineages tend to resist/fight infections better than more recently diverged coral lineages. This result, combined with the increasing stressful conditions on corals in the Caribbean, suggest that future reefs in the region will likely be dominated by older lineages while modern species may face local population declines and/or geographic extinction. PMID- 25133686 TI - Transferred BCR/ABL DNA from K562 extracellular vesicles causes chronic myeloid leukemia in immunodeficient mice. AB - Our previous study showed that besides mRNAs and microRNAs, there are DNA fragments within extracellular vesicles (EVs). The BCR/ABL hybrid gene, involved in the pathogenesis of chronic myeloid leukemia (CML), could be transferred from K562 EVs to neutrophils and decrease their phagocytic activity in vitro. Our present study provides evidence that BCR/ABL DNAs transferred from EVs have pathophysiological significance in vivo. Two months after injection of K562 EVs into the tail vein of Sprague-Dawley (SD) rats, they showed some characteristics of CML, e.g., feeble, febrile, and thin, with splenomegaly and neutrophilia but with reduced neutrophil phagocytic activity. These findings were also observed in immunodeficient NOD/SCID mice treated with K562 EVs; BCR/ABL mRNA and protein were found in their neutrophils. The administration of actinomycin D, an inhibitor of de novo mRNA synthesis, prevented the abnormalities caused by K562 EVs in NOD/SCID mice related to CML, including neutrophilia and bone marrow hyperplasia. As a specific inhibitor of tyrosine kinases, imatinib blocked the activity of tyrosine kinases and the expression of phospho-Crkl, induced by the de novo BCR/ABL protein caused by K562 EVs bearing BCR/ABL DNA. Our current study shows the pathophysiological significance of transferred tumor gene from EVs in vivo, which may represent an important mechanism for tumorigenesis, tumor progression, and metastasis. PMID- 25133687 TI - Galleria mellonella model identifies highly virulent strains among all major molecular types of Cryptococcus gattii. AB - Cryptococcosis is mainly caused by Cryptococcus neoformans. However, the number of cases due to C. gattii is increasing, affecting mainly immunocompetent hosts. C. gattii is divided into four major molecular types, VGI to VGIV, which differ in their host range, epidemiology, antifungal susceptibility and geographic distribution. Besides studies on the Vancouver Island outbreak strains, which showed that the subtype VGIIa is highly virulent compared to the subtype VGIIb, little is known about the virulence of the other major molecular types. To elucidate the virulence potential of the major molecular types of C. gattii, Galleria mellonella larvae were inoculated with ten globally selected strains per molecular type. Survival rates were recorded and known virulence factors were studied. One VGII, one VGIII and one VGIV strain were more virulent (p <0.05) than the highly virulent Vancouver Island outbreak strain VGIIa (CDCR265), 11 (four VGI, two VGII, four VGIII and one VGIV) had similar virulence (p >0.05), 21 (five VGI, five VGII, four VGIII and seven VGIV) were less virulent (p <0.05) while one strain of each molecular type were avirulent. Cell and capsule size of all strains increased markedly during larvae infection (p <0.001). No differences in growth rate at 37 degrees C were observed. Melanin synthesis was directly related with the level of virulence: more virulent strains produced more melanin than less virulent strains (p <0.05). The results indicate that all C. gattii major molecular types exhibit a range of virulence, with some strains having the potential to be more virulent. The study highlights the necessity to further investigate the genetic background of more and less virulent strains in order to recognize critical features, other than the known virulence factors (capsule, melanin and growth at mammalian body temperature), that maybe crucial for the development and progression of cryptococcosis. PMID- 25133689 TI - Lack of evidence for lower mercury biomagnification by biomass dilution in more productive lakes: comment on "Mercury biomagnification through food webs is affected by physical and chemical characteristics of lakes". PMID- 25133691 TI - Two-dimensional TaSe2 metallic crystals: spin-orbit scattering length and breakdown current density. AB - We have determined the spin-orbit scattering length of two-dimensional layered 2H TaSe2 metallic crystals by detailed characterization of the weak antilocalization phenomena in this strong spin-orbit interaction material. By fitting the observed magneto-conductivity, the spin-orbit scattering length for 2H-TaSe2 is determined to be 17 nm in the few-layer films. This small spin-orbit scattering length is comparable to that of Pt, which is widely used to study the spin Hall effect, and indicates the potential of TaSe2 for use in spin Hall effect devices. A material must also support large charge currents in addition to strong spin-orbit coupling to achieve spin-transfer-torque via the spin Hall effect. Therefore, we have characterized the room temperature breakdown current density of TaSe2 in air, where the best breakdown current density reaches 3.7 * 10(7) A/cm(2). This large breakdown current further indicates the potential of TaSe2 for use in spin-torque devices and two-dimensional device interconnect applications. PMID- 25133690 TI - Episodic bradycardia as neurocardiac prodrome to voltage-gated potassium channel complex/leucine-rich, glioma inactivated 1 antibody encephalitis. AB - IMPORTANCE: Voltage-gated potassium channel complex antibody (VGKCc-Ab) encephalitis is an immunotherapy-responsive syndrome usually associated with causative antibodies that target the leucine-rich, glioma inactivated 1 (LGI1) protein. Although it is expressed throughout the brain, LGI1 is not known to be expressed in cardiac tissue. We describe a novel neurocardiac prodrome of VGKCc Ab/LGI1-encephalitis. OBSERVATIONS: Among 14 patients with VGKCc/LGI1-Ab encephalitis evaluated in the University of California, San Francisco Autoimmune Encephalitis Clinic and Rapid Dementia Research Program, 3 patients (2 men and 1 woman; aged 53, 55, and 64 years) exhibited episodic bradycardia that preceded the onset of encephalopathy by approximately 2 months and was severe enough to lead to pacemaker implantation. Serum LGI1-Ab results were positive when tested at the time of the subsequent encephalopathy. All 3 patients developed hyponatremia; none had faciobrachial dystonic seizures or malignancy. Brain magnetic resonance imaging was abnormal in 2 cases. None of the patients experienced further symptomatic bradyarrythmias after 1.7 to 7 years of follow up. CONCLUSIONS AND RELEVANCE: Episodic bradycardia is a distinctive neurocardiac prodrome of VGKCc/LGI1-Ab encephalitis. The neuroanatomical localization most likely relates to insular and temporal lobe involvement, cortical regions that modulate cardiac autonomic function. Further study is needed to determine if recognition of this neurocardiac prodrome and earlier institution of immunosuppression can prevent the development of encephalopathy. PMID- 25133692 TI - Diabetes mellitus aggravates hemorrhagic transformation after ischemic stroke via mitochondrial defects leading to endothelial apoptosis. AB - Diabetes is a crucial risk factor for stroke and is associated with increased frequency and poor prognosis. Although endothelial dysfunction is a known contributor of stroke, the underlying mechanisms have not been elucidated. The aim of this study was to elucidate the mechanism by which chronic hyperglycemia may contribute to the worsened prognosis following stroke, especially focusing on mitochondrial alterations. We examined the effect of hyperglycemia on hemorrhagic transformation at 24 hours after middle cerebral artery occlusion (MCAO) in streptozotocin (STZ) -induced diabetic mice. We also examined the effects of high glucose exposure for 6 days on cell death, mitochondrial functions and morphology in human brain microvascular endothelial cells (HBMVECs) or human endothelial cells derived from induced pluripotent stem cells (iCell endothelial cells). Hyperglycemia aggravated hemorrhagic transformation, but not infarction following stroke. High-glucose exposure increased apoptosis, capase-3 activity, and release of apoptosis inducing factor (AIF) and cytochrome c in HBMVECs as well as affected mitochondrial functions (decreased cell proliferation, ATP contents, mitochondrial membrane potential, and increased matrix metalloproteinase (MMP)-9 activity, but not reactive oxygen species production). Furthermore, morphological aberration of mitochondria was observed in diabetic cells (a great deal of fragmentation, vacuolation, and cristae disruption). A similar phenomena were seen also in iCell endothelial cells. In conclusion, chronic hyperglycemia aggravated hemorrhagic transformation after stroke through mitochondrial dysfunction and morphological alteration, partially via MMP-9 activation, leading to caspase-dependent apoptosis of endothelial cells of diabetic mice. Mitochondria-targeting therapy may be a clinically innovative therapeutic strategy for diabetic complications in the future. PMID- 25133688 TI - Targeting the ubiquitin-proteasome system in heart disease: the basis for new therapeutic strategies. AB - SIGNIFICANCE: Novel therapeutic strategies to treat heart failure are greatly needed. The ubiquitin-proteasome system (UPS) affects the structure and function of cardiac cells through targeted degradation of signaling and structural proteins. This review discusses both beneficial and detrimental consequences of modulating the UPS in the heart. RECENT ADVANCES: Proteasome inhibitors were first used to test the role of the UPS in cardiac disease phenotypes, indicating therapeutic potential. In early cardiac remodeling and pathological hypertrophy with increased proteasome activities, proteasome inhibition prevented or restricted disease progression and contractile dysfunction. Conversely, enhancing proteasome activities by genetic manipulation, pharmacological intervention, or ischemic preconditioning also improved the outcome of cardiomyopathies and infarcted hearts with impaired cardiac and UPS function, which is, at least in part, caused by oxidative damage. CRITICAL ISSUES: An understanding of the UPS status and the underlying mechanisms for its potential deregulation in cardiac disease is critical for targeted interventions. Several studies indicate that type and stage of cardiac disease influence the dynamics of UPS regulation in a nonlinear and multifactorial manner. Proteasome inhibitors targeting all proteasome complexes are associated with cardiotoxicity in humans. Furthermore, the type and dosage of proteasome inhibitor impact the pathogenesis in nonuniform ways. FUTURE DIRECTIONS: Systematic analysis and targeting of individual UPS components with established and innovative tools will unravel and discriminate regulatory mechanisms that contribute to and protect against the progression of cardiac disease. Integrating this knowledge in drug design may reduce adverse effects on the heart as observed in patients treated with proteasome inhibitors against noncardiac diseases, especially cancer. PMID- 25133695 TI - Complete mitochondrial genome sequence of the longsnout seahorse Hippocampus reidi (Ginsburg, 1933; Gasterosteiformes: Syngnathidae). AB - The complete mitochondrial genome sequence of the longsnout seahorse Hippocampus reidi was fisrt determined in this article. The total length of H. reidi mitogenome is 16,529 bp and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region. The gene order and composition of H. reidi were similar to those of most other vertebrates. The overall base composition of H. reidi is 32.47% A, 29.41% T, 14.75% G and 23.37% C, with a slight A + T rich feature (61.88%). PMID- 25133694 TI - The minor wall-networks between monolignols and interlinked-phenolics predominantly affect biomass enzymatic digestibility in Miscanthus. AB - Plant lignin is one of the major wall components that greatly contribute to biomass recalcitrance for biofuel production. In this study, total 79 representative Miscanthus germplasms were determined with wide biomass digestibility and diverse monolignol composition. Integrative analyses indicated that three major monolignols (S, G, H) and S/G ratio could account for lignin negative influence on biomass digestibility upon NaOH and H2SO4 pretreatments. Notably, the biomass enzymatic digestions were predominately affected by the non KOH-extractable lignin and interlinked-phenolics, other than the KOH-extractable ones that cover 80% of total lignin. Furthermore, a positive correlation was found between the monolignols and phenolics at p<0.05 level in the non-KOH extractable only, suggesting their tight association to form the minor wall networks against cellulases accessibility. The results indicated that the non-KOH extractable lignin-complex should be the target either for cost-effective biomass pretreatments or for relatively simply genetic modification of plant cell walls in Miscanthus. PMID- 25133693 TI - Dopamine D2-like receptors modulate unconditioned fear: role of the inferior colliculus. AB - BACKGROUND: A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system clearly reduces conditioned fear. Injections of haloperidol, a preferential D2 receptor antagonist, into the inferior colliculus (IC) enhance the processing of unconditioned aversive information. However, a clear characterization of the interplay of D2 receptors in the mediation of unconditioned and conditioned fear is still lacking. METHODS: The present study investigated the effects of intra-IC injections of the D2 receptor-selective antagonist sulpiride on behavior in the elevated plus maze (EPM), auditory-evoked potentials (AEPs) to loud sounds recorded from the IC, fear-potentiated startle (FPS), and conditioned freezing. RESULTS: Intra-IC injections of sulpiride caused clear proaversive effects in the EPM and enhanced AEPs induced by loud auditory stimuli. Intra-IC sulpiride administration did not affect FPS or conditioned freezing. CONCLUSIONS: Dopamine D2-like receptors of the inferior colliculus play a role in the modulation of unconditioned aversive information but not in the fear-potentiated startle response. PMID- 25133696 TI - The complete mitogenome of Xenophysogobio boulengeri (Cypriniformes; Cyprinidae). AB - Xenophysogobio boulengeri is an endemic fish to mainstream and most tributaries of the upper Yangtze River. The complete mitochondrial genome sequence of X. boulengeri has been amplified and sequenced. The mitochondrial genome sequence was 16,611 bp, and the gene order and contents were identical with that of other previously reported fish with 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes, and a non-coding control region. Most of genes were encoded by Heavy Strand (H-strand), except 8 tRNA and ND6 genes, which were encoded by Light Strand (L-strand). Base composition of the genome was A (30.8%), T (27.0%), C (25.8%) and G (16.4%) with an A+T rich feature as that of other vertebrate mitochondrial genomes. PMID- 25133697 TI - The complete mitochondrial genome of the hybrid of Siniperca chuatsi (?) * Siniperca kneri (?). AB - In this study, we reported the complete mitochondrial DNA sequence of the hybrid of Siniperca chuatsi (?)*Siniperca kneri (?). The total length of the mitochondrial genome is 16,493 bp, with the base composition of 28.61% A, 29.21% C, 16.21% G, and 25.97% T. It contains 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes, and a major non-coding control region (D-loop region). The composition and order of these genes are identical to most of other vertebrates. All the protein initiation codons are ATG, except for COX1 that begins with GTG. The complete mitogenome of the hybrid of Siniperca chuatsi (?) * Siniperca kneri (?) provides an important data set for the study in genetic mechanism. PMID- 25133698 TI - The complete mitogenome of Gnathopogon polytaenia (Cypriniformes; Cyprinidae). AB - The complete mitochondrial genome was sequenced from one of the endemic freshewater gudgeons (Gnathopogon polytaenia) in China. The mitochondrial genome sequence was 16,594 bp in size, and the gene order and contents were identical with the congeneric species G. strigatus and G. elongatus. Six genes (COII, ATP6, COIII, ND3, ND4, Cytb) had an incomplete stop codon. Base composition of the genome is A (29.1%), T (26.9%), C (25.9%) and G (18.1%) with an A + T rich feature (56%) as that of other vertebrate mitochondrial genomes. PMID- 25133700 TI - Ultrasound-assisted sequential multicomponent strategy for the combinatorial synthesis of novel coumarin hybrids. AB - The present investigation reports an easy access to a library of novel spiro oxindole-pyrrolizine or pyrrolo[1,2-c]thiazole fused coumarin hybrid heterocycles through a one-pot sequential four-component reactions of 2,2-dimethyl-1,3-dioxane 4,6-dione, salicylaldehydes, isatins, and cyclic alpha-amino acids under ultrasound irradiation. PMID- 25133699 TI - A novel glycated hemoglobin A1c-lowering traditional Chinese medicinal formula, identified by translational medicine study. AB - Diabetes is a chronic metabolic disorder that has a significant impact on the health care system. The reduction of glycated hemoglobin A1c is highly associated with the improvements of glycemic control and diabetic complications. In this study, we identified a traditional Chinese medicinal formula with a HbA1c lowering potential from clinical evidences. By surveying 9,973 diabetic patients enrolled in Taiwan Diabetic Care Management Program, we found that Chu-Yeh-Shih Kao-Tang (CYSKT) significantly reduced HbA1c values in diabetic patients. CYSKT reduced the levels of HbA1c and fasting blood glucose, and stimulated the blood glucose clearance in type 2 diabetic mice. CYSKT affected the expressions of genes associated with insulin signaling pathway, increased the amount of phosphorylated insulin receptor in cells and tissues, and stimulated the translocation of glucose transporter 4. Moreover, CYSKT affected the expressions of genes related to diabetic complications, improved the levels of renal function indexes, and increased the survival rate of diabetic mice. In conclusion, this was a translational medicine study that applied a "bedside-to-bench" approach to identify a novel HbA1c-lowering formula. Our findings suggested that oral administration of CYSKT affected insulin signaling pathway, decreased HbA1c and blood glucose levels, and consequently reduced mortality rate in type 2 diabetic mice. PMID- 25133701 TI - Zonisamide: pharmacokinetics, efficacy, and adverse events in children with epilepsy. AB - BACKGROUND: Zonisamide is a new generation antiepileptic drug (AED) widely used in children with refractory epilepsy, although until recently, it was used to a large extent as off-label or unlicensed medication due to the lack of evidence based studies. Children have a different pharmacokinetic profile than adults and an adult dose regimen cannot be directly translated into pediatric use. Patients and METHODS: In this retrospective noninterventional study of the medical records of 75 children with pharmacoresistant epilepsy, the pharmacokinetics, efficacy and safety of zonisamide were examined. The dose-to-concentration ratio, the daily weight-normalized dose of zonisamide divided by its plasma concentration, was used as a measure of clearance. In addition, data on the efficacy of zonisamide to reduce seizures and reported adverse events were extracted from the medical records and analyzed. RESULTS: Young children (range, 0-4 years) had a significantly increased zonisamide clearance compared with older ones (range, 5 17 years) and those with enzyme-inducing comedication (carbamazepine, phenobarbital, or phenytoin) had increased clearance compared with those on nonenzyme inducers; the increases were 1.7-fold and 1.8-fold, respectively. No significant difference in clearance was found between female and male subjects. The clearances of concomitant AEDs were not affected by zonisamide administration. The overall efficacy of zonisamide for reducing seizure frequency >= 50% was 35% and the most frequent adverse event was fatigue, reported in 23% of the patients. CONCLUSION: Patients with enzyme-inducing comedication or of young age (range, 0-4 years) might need higher weight-normalized doses to achieve the same plasma levels as in patients with no enzyme-inducing comedication or patients of older age. Zonisamide was not found to influence the pharmacokinetics of concomitant AEDs. The shortage of pharmacokinetic studies of zonisamide in children highlights the need for research of this kind. PMID- 25133702 TI - Surprising quenching of the spin-orbit interaction significantly diminishes H2O...X [X = F, Cl, Br, I] dissociation energies. AB - The H2O...X complexes, with X = F, Cl, Br, and I, show considerable viability with nonspin-orbit De(D0) dissociation energy values of 3.73(2.42), 3.60(2.68), 3.54(2.72), and 3.36(2.77) kcal mol(-1) for X = F, Cl, Br, and I, respectively, obtained at the CCSD(T)-F12b/aug-cc-pVTZ(-PP) level of theory using relativistic pseudopotentials (PPs) for Br and I. Spin-orbit (SO) corrections, computed with the Breit-Pauli operator in the interacting states approach at the all-electron MRCI+Q/aug-cc-pwCVTZ(-PP) level, are found to depend sensitively and unpredictably on the O...X separations. 96% (F), 87% (Cl), 54% (Br), and 30% (I) quenching of the SO corrections significantly reduces the dissociation energies of the H2O...X complexes, resulting in De(D0) values of 3.38(2.06), 2.86(1.94), 1.64(0.83), and 1.23(0.64) kcal mol(-1) for X = F, Cl, Br, and I, respectively. PMID- 25133703 TI - Nanoparticle surface characterization and clustering through concentration dependent surface adsorption modeling. AB - Quantitative characterization of nanoparticle interactions with their surrounding environment is vital for safe nanotechnological development and standardization. A recent quantitative measure, the biological surface adsorption index (BSAI), has demonstrated promising applications in nanomaterial surface characterization and biological/environmental prediction. This paper further advances the approach beyond the application of five descriptors in the original BSAI to address the concentration dependence of the descriptors, enabling better prediction of the adsorption profile and more accurate categorization of nanomaterials based on their surface properties. Statistical analysis on the obtained adsorption data was performed based on three different models: the original BSAI, a concentration dependent polynomial model, and an infinite dilution model. These advancements in BSAI modeling showed a promising development in the application of quantitative predictive modeling in biological applications, nanomedicine, and environmental safety assessment of nanomaterials. PMID- 25133705 TI - Detection and molecular characterization of infectious bronchitis-like viruses in wild bird populations. AB - We examined 884 wild birds mainly from the Anseriformes, Charadriiformes and Galliformes orders for infectious bronchitis (IBV)-like coronavirus in Poland between 2008 and 2011. Coronavirus was detected in 31 (3.5%) of the tested birds, with detection rates of 3.5% in Anseriformes and 2.3% in Charadriiformes and as high as 17.6% in Galliformes. From the 31 positive samples, only 10 gave positive results in molecular tests aimed at various IBV genome fragments: five samples were positive for the RdRp gene, four for gene 3, eight for gene N and eight for the 3'-untranslated region fragment. All analysed genome fragments of the coronavirus strains shared different evolutionary branches, resulting in a different phylogenetic tree topology. Most detected fragment genes seem to be IBV like genes of the most frequently detected lineages of IBV in this geographical region (i.e. Massachusetts, 793B and QX). Two waves of coronavirus infections were identified: one in spring (April and May) and another in late autumn (October to December). To our knowledge this is the first report of the detection of different fragment IBV-like genes in wild bird populations. PMID- 25133704 TI - Molecular dynamics study of binding of u-conotoxin GIIIA to the voltage-gated sodium channel Na(v)1.4. AB - Homology models of mammalian voltage-gated sodium (NaV) channels based on the crystal structures of the bacterial counterparts are needed to interpret the functional data on sodium channels and understand how they operate. Such models would also be invaluable in structure-based design of therapeutics for diseases involving sodium channels such as chronic pain and heart diseases. Here we construct a homology model for the pore domain of the NaV1.4 channel and use the functional data for the binding of u-conotoxin GIIIA to NaV1.4 to validate the model. The initial poses for the NaV1.4-GIIIA complex are obtained using the HADDOCK protein docking program, which are then refined in molecular dynamics simulations. The binding mode for the final complex is shown to be in broad agreement with the available mutagenesis data. The standard binding free energy, determined from the potential of mean force calculations, is also in good agreement with the experimental value. Because the pore domains of NaV1 channels are highly homologous, the model constructed for NaV1.4 will provide an excellent template for other NaV1 channels. PMID- 25133706 TI - High-grade endometrial stromal sarcomas: a clinicopathologic study of a group of tumors with heterogenous morphologic and genetic features. AB - The existence of a "high-grade endometrial stromal sarcoma" category of tumors has been a controversial subject owing to, among other things, the difficulty in establishing consistent diagnostic criteria. Currently, the recommended classification for such tumors is undifferentiated uterine/endometrial sarcoma. Interest in this subject has recently increased markedly with the identification of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of neoplasms has been observed that morphologically resemble, either cytologically or architecturally, classic "low-grade" endometrial stromal sarcoma but feature obvious deviations, specifically, 17 tumors with unequivocally high-grade morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors with a component that is identical to low-grade ESS that transitions abruptly into an obviously higher-grade component; (2) tumors composed exclusively of high grade cells with uniform nuclear features but with a permeative pattern of infiltration; (3) tumors similar to the second group but with a different, yet characteristic, cytomorphology featuring enlarged round to ovoid cells (larger than those found in low-grade ESS) with smooth nuclear membranes and distinct chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic data, applied immunohistochemical studies, and also tested tumors by fluorescence in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors from these 3 groups were found to be immunohistochemically and genetically distinct from one another. Most notable was the fact that category 3 contained all the cases that tested positive for YWHAE rearrangement, did not show any classic translocations for JAZF1, PHF1, or CCND1, often presented at a high stage, and behaved aggressively. This study demonstrates the morphologic, immunophenotypic, and molecular genetic heterogeneity that exists within "undifferentiated endometrial sarcomas" as currently defined and lends credence to the effort of subclassifying some tumors as truly "high-grade endometrial stromal sarcomas." Our study also shows that, in the context of undifferentiated endometrial sarcomas, recognition of cytomorphologic features on routine hematoxylin and eosin-stained sections may be used to select tumors with specific molecular genetic changes-that is, translocations involving YWHAE. Our conclusions will help further efforts towards proper sub-classification of these tumors which will aid in diagnosis and potentially affect clinical management. PMID- 25133707 TI - Assessing the HER2 status in mucinous epithelial ovarian cancer on the basis of the 2013 ASCO/CAP guideline update. AB - Her2 gene amplification and protein overexpression are important factors in predicting clinical sensitivity to anti-HER2 monoclonal antibody therapy in breast, gastric, or gastro-esophageal junction cancer patients. The purpose of this study was to evaluate the HER2 status in the mucinous epithelial ovarian cancer (EOC). Adopting the 2013 American Society for Clinical Oncology and the College of American Pathologists guideline update for HER2 testing, 49 tissue microarray samples of mucinous EOC were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests. The prevalence of HER2 positivity in Asian mucinous EOC was 9 of 49 Asian women (18.37%). The overall concordance was 100% between IHC and FISH results. Her2 gene copies before chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal, and positive IHC result categories (P<0.001), as did the Her2 gene copies after chromosome-17 correction (P<0.001). Of the Taiwanese cohort (n=21), HER2 heterogeneity was 4.76% (1/21) in all but 14.26% (1/7) in HER2-positive cancer. In conclusion, we demonstrated that the prevalence of HER2 positivity in both Asian and white women was comparable; complete HER2 concordance existed between IHC and FISH tests for the Her2 gene copies per tumor cell either before or after correction of chromosome-17, and this can be applied as a potentially valuable tool to analyze the HER2 status. Polysomy-17 was absent under the CEP17 cutoff >=3. The existence of HER2 heterogeneity can be discerned in certain HER2-expressed primary mucinous EOC in Taiwanese women. PMID- 25133708 TI - Pseudoangiosarcomatous urothelial carcinoma of the urinary bladder. AB - The pseudoangiosarcomatous pattern has been described mostly in cutaneous and some visceral squamous cell carcinomas and is unique for its striking morphologic resemblance to angiosarcoma. Herein, we describe the clinicopathologic features of 7 pseudoangiosarcomatous urothelial carcinomas that occurred in the urinary bladder. The patients included 6 men and 1 woman ranging in age from 47 to 87 years (median 70 y). The pseudoangiosarcomatous morphology was observed in 7 urothelial carcinomas including 3 with squamous differentiation and comprised 35% to 85% of the invasive tumor. Histologically, the pseudoangiosarcomatous carcinomas were characterized by tumor cell discohesion and lysis that created pseudolumina formations surrounded by attached residual tumor cells. Detached degenerating tumor cells variably admixed with inflammatory cells were common in the false lumina. Partly intact urothelial carcinoma nests contained irregular or cleft-like spaces and disintegrating tumor cells with stretched intercellular bridges. The tumor was commonly associated with a dense collagenous matrix, often surrounding the lytic nests. Similar tumor cell discohesion and breakdown were observed in 3 tumors with foci of squamous cell differentiation, distinguished by the presence of dyskeratosis and keratin formation. All 7 tumors contained other nonpseudoangiosarcomatous carcinoma components such as conventional urothelial carcinoma (5), squamous differentiation (4), sarcomatoid spindle cell carcinoma (2), small cell carcinoma (1), micropapillary carcinoma (1), and glandular differentiation (1). The pseudoangiosarcomatous urothelial carcinomas were all (7/7) diffusely CK7 positive, most (6/7) were GATA3 positive, and none (0/7) expressed vascular-associated markers. There was no evidence to suggest that apoptosis (by TUNEL assay and cleaved caspase-3 immunostaining) or loss of the adhesion molecules CD138 and e-cadherin were possible causes for the tumor cell discohesion and breakdown. All 7 tumors were high stage at cystectomy and included 1 pT3a, 2 pT3b, and 4 pT4a tumors, and 3 had pelvic lymph node involvement. Follow-up data available in 6 cases revealed a poor outcome with an overall median survival of 8.5 months. In conclusion, we present an unusual morphology of bladder carcinoma that has a striking resemblance to a malignant vasoformative tumor. Our series showed that bladder pseudoangiosarcomatous carcinoma morphology is associated with a higher tumor stage at cystectomy, commonly admixed with other aggressive carcinoma variant morphologies, and portend a poorer outcome. Knowledge of this pattern is also important to avoid misdiagnosis, particularly in limited tissue samples. PMID- 25133709 TI - Health-related quality of life measurement in siblings of children with physical chronic illness: a systematic review. AB - The diagnosis of a physical chronic illness during childhood can cause stressors and changes within the family system that place family members at-risk for impaired functioning. The objective of the present study was to perform a systematic review on the health-related quality of life (HRQOL) of siblings of children with physical chronic health conditions. Three independent reviewers performed the search in the databases PsycINFO and PubMed, which resulted in 9 studies meeting full inclusion criteria. Overall, sibling HRQOL was better than children with a physical chronic illness. Parents of siblings of children with physical chronic illness tended to rate sibling HRQOL better than siblings self reports. Greater disease severity emerged as a potential risk factor for impaired sibling HRQOL. These data underscore the importance of assessing sibling HRQOL in families with a child who has been diagnosed with a physical chronic illness. Future research is needed in this area with larger sibling samples and across a greater variety of childhood chronic illnesses. PMID- 25133710 TI - Protein supplementation increases postexercise plasma myostatin concentration after 8 weeks of resistance training in young physically active subjects. AB - Myostatin (MSTN) is a negative regulator of muscle growth even if some studies have shown a counterintuitive positive correlation between MSTN and muscle mass (MM). Our aim was to investigate the influence of 2 months of resistance training (RT) and diets with different protein contents on plasma MSTN, interleukin 1 beta (IL-1beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and insulin-like growth factor 1 (IGF-1). Eighteen healthy volunteers were randomly divided in two groups: high protein (HP) and normal protein (NP) groups. Different protein diet contents were 1.8 and 0.85 g of protein.kg bw(-1).day(-1) for HP and NP, respectively. Subjects underwent 8 weeks of standardized progressive RT. MSTN, IGF-1, IL-1beta, IL-6, and TNF-alpha were analyzed before and after the first and the last training sessions. Lean body mass, MM, upper limb muscle area, and strength were measured. Plasma MSTN showed a significant increase (P<.001) after the last training in the HP group compared with NP group and with starting value. IGF-1 plasma concentration showed a positive correlation with MSTN in HP after the last training (r(2)=0.6456; P=.0295). No significant differences were found between NP and HP for IL-1beta, IL-6, TNF-alpha, and strength and MM or area. These findings suggest a "paradoxical" postexercise increase of plasma MSTN after 8 weeks of RT and HP diets. This MSTN elevation correlates positively with IGF-1 plasma level. This double increase of opposite (catabolic/anabolic) mediators could explain the substantial overlapping of MM increases in the two groups. PMID- 25133712 TI - Phylogenetic analyses and characterization of RNase X25 from Drosophila melanogaster suggest a conserved housekeeping role and additional functions for RNase T2 enzymes in protostomes. AB - Ribonucleases belonging to the RNase T2 family are enzymes associated with the secretory pathway that are almost absolutely conserved in all eukaryotes. Studies in plants and vertebrates suggest they have an important housekeeping function in rRNA recycling. However, little is known about this family of enzymes in protostomes. We characterized RNase X25, the only RNase T2 enzyme in Drosophila melanogaster. We found that RNase X25 is the major contributor of ribonuclease activity in flies as detected by in gel assays, and has an acidic pH preference. Gene expression analyses showed that the RNase X25 transcript is present in all adult tissues and developmental stages. RNase X25 expression is elevated in response to nutritional stresses; consistent with the hypothesis that this enzyme has a housekeeping role in recycling RNA. A correlation between induction of RNase X25 expression and autophagy was observed. Moreover, induction of gene expression was triggered by oxidative stress suggesting that RNase X25 may have additional roles in stress responses. Phylogenetic analyses of this family in protostomes showed that RNase T2 genes have undergone duplication events followed by divergence in several phyla, including the loss of catalytic residues, and suggest that RNase T2 proteins have acquired novel functions. Among those, it is likely that a role in host immunosuppression evolved independently in several groups, including parasitic Platyhelminthes and parasitoid wasps. The presence of only one RNase T2 gene in the D. melanogaster genome, without any other evident secretory RNase activity detected, makes this organism an ideal system to study the cellular functions of RNase T2 proteins associated with RNA recycling and maintenance of cellular homeostasis. On the other hand, the discovery of gene duplications in several protostome genomes also presents interesting new avenues to study additional biological functions of this ancient family of proteins. PMID- 25133715 TI - The Situational Eight DIAMONDS: a taxonomy of major dimensions of situation characteristics. AB - Taxonomies of person characteristics are well developed, whereas taxonomies of psychologically important situation characteristics are underdeveloped. A working model of situation perception implies the existence of taxonomizable dimensions of psychologically meaningful, important, and consequential situation characteristics tied to situation cues, goal affordances, and behavior. Such dimensions are developed and demonstrated in a multi-method set of 6 studies. First, the "Situational Eight DIAMONDS" dimensions Duty, Intellect, Adversity, Mating, pOsitivity, Negativity, Deception, and Sociality (Study 1) are established from the Riverside Situational Q-Sort (Sherman, Nave, & Funder, 2010, 2012, 2013; Wagerman & Funder, 2009). Second, their rater agreement (Study 2) and associations with situation cues and goal/trait affordances (Studies 3 and 4) are examined. Finally, the usefulness of these dimensions is demonstrated by examining their predictive power of behavior (Study 5), particularly vis-a-vis measures of personality and situations (Study 6). Together, we provide extensive and compelling evidence that the DIAMONDS taxonomy is useful for organizing major dimensions of situation characteristics. We discuss the DIAMONDS taxonomy in the context of previous taxonomic approaches and sketch future research directions. PMID- 25133714 TI - Observing a movement correction during walking affects evoked responses but not unperturbed walking. AB - Seeing an action activates neurons in the premotor, motor, and somatosensory cortex. Since a significant fraction of these pyramidal neurons project to the spinal motor circuits, a central question is why we do not automatically perform the actions that we see. Indeed, seeing an action increases both cortical and spinal excitability of consistent motor patterns that correspond to the observed ones. Thus, it is believed that such imitative motor patterns are either suppressed or remain at a sub-threshold level. This would predict, however, that seeing someone make a corrective movement while one is actively involved in the same action should either suppress evoked responses or suppress or modulate the action itself. Here we tested this prediction, and found that seeing someone occasionally stepping over an obstacle while walking on a treadmill did not affect the normal walking pattern at all. However, cutaneously evoked reflexes in the anterior tibial and soleus muscles were modulated as if the subject was stepping over an obstacle. This result thus indicates that spinal activation was not suppressed and was neither at sub-threshold motor resonance. Rather, the spinal modulation from observed stepping reflects an adaptive mechanism for regulating predictive control mechanisms. We conclude that spinal excitability during action observation is not an adverse side-effect of action understanding but reflects adaptive and predictive motor control. PMID- 25133716 TI - Moral character in the workplace. AB - Using two 3-month diary studies and a large cross-sectional survey, we identified distinguishing features of adults with low versus high levels of moral character. Adults with high levels of moral character tend to: consider the needs and interests of others and how their actions affect other people (e.g., they have high levels of Honesty-Humility, empathic concern, guilt proneness); regulate their behavior effectively, specifically with reference to behaviors that have positive short-term consequences but negative long-term consequences (e.g., they have high levels of Conscientiousness, self-control, consideration of future consequences); and value being moral (e.g., they have high levels of moral identity-internalization). Cognitive moral development, Emotionality, and social value orientation were found to be relatively undiagnostic of moral character. Studies 1 and 2 revealed that employees with low moral character committed harmful work behaviors more frequently and helpful work behaviors less frequently than did employees with high moral character, according to their own admissions and coworkers' observations. Study 3 revealed that adults with low moral character committed more delinquent behavior and had more lenient attitudes toward unethical negotiation tactics than did adults with high moral character. By showing that individual differences have consistent, meaningful effects on employees' behaviors, after controlling for demographic variables (e.g., gender, age, income) and basic attributes of the work setting (e.g., enforcement of an ethics code), our results contest situationist perspectives that deemphasize the importance of personality. Moral people can be identified by self-reports in surveys, and these self-reports predict consequential behaviors months after the initial assessment. PMID- 25133713 TI - Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism. AB - Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). We found that prenatal exposure of valproic acid (VPA) induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE) in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs) such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg) intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance. PMID- 25133718 TI - "I'd only let you down": Guilt proneness and the avoidance of harmful interdependence. AB - Five studies demonstrated that highly guilt-prone people may avoid forming interdependent partnerships with others whom they perceive to be more competent than themselves, as benefitting a partner less than the partner benefits one's self could trigger feelings of guilt. Highly guilt-prone people who lacked expertise in a domain were less willing than were those low in guilt proneness who lacked expertise in that domain to create outcome-interdependent relationships with people who possessed domain-specific expertise. These highly guilt-prone people were more likely than others both to opt to be paid on their performance alone (Studies 1, 3, 4, and 5) and to opt to be paid on the basis of the average of their performance and that of others whose competence was more similar to their own (Studies 2 and 5). Guilt proneness did not predict people's willingness to form outcome-interdependent relationships with potential partners who lacked domain-specific expertise (Studies 4 and 5). It also did not predict people's willingness to form relationships when poor individual performance would not negatively affect partner outcomes (Study 4). Guilt proneness therefore predicts whether, and with whom, people develop interdependent relationships. The findings also demonstrate that highly guilt-prone people sacrifice financial gain out of concern about how their actions would influence others' welfare. As such, the findings demonstrate a novel way in which guilt proneness limits free-riding and therefore reduces the incidence of potentially unethical behavior. Lastly, the findings demonstrate that people who lack competence may not always seek out competence in others when choosing partners. PMID- 25133717 TI - Sense of control under uncertainty depends on people's childhood environment: a life history theory approach. AB - Past research found that environmental uncertainty leads people to behave differently depending on their childhood environment. For example, economic uncertainty leads people from poor childhoods to become more impulsive while leading people from wealthy childhoods to become less impulsive. Drawing on life history theory, we examine the psychological mechanism driving such diverging responses to uncertainty. Five experiments show that uncertainty alters people's sense of control over the environment. Exposure to uncertainty led people from poorer childhoods to have a significantly lower sense of control than those from wealthier childhoods. In addition, perceptions of control statistically mediated the effect of uncertainty on impulsive behavior. These studies contribute by demonstrating that sense of control is a psychological driver of behaviors associated with fast and slow life history strategies. We discuss the implications of this for theory and future research, including that environmental uncertainty might lead people who grew up poor to quit challenging tasks sooner than people who grew up wealthy. PMID- 25133719 TI - Accuracy and bias in self-perceptions of responsive behavior: implications for security in romantic relationships. AB - The current research examined self-perception of responsive behavior as a process through which perceivers who highly value romantic partners generate security that they are valued by those partners. People hold naive theories that their responsive behavior elicits positive sentiments from others, such as satisfaction, positive regard, and commitment, and they believe their unresponsive behavior elicits negative sentiments. Accordingly, 2 dyadic behavioral observation studies, one involving conflict interactions (Study 1) and one involving support interactions (Study 2), suggested that people who value partners achieve security that they are valued by their partners through both accurate and biased self-perceptions of responsive behavior. Perceivers who valued partners accurately perceived their more responsive behavior enacted toward partners, which bolstered their confidence that they were valued by partners (accurate self-perception). In addition, perceivers who valued partners had biased and exaggerated perceptions of their own responsive behavior, which also bolstered their perceptions of being valued by partners (biased self perception). Examination of memories of responsive behavior 2 weeks and 6 months following interactions (Study 2) suggested that perceivers' memories of their own responsive behavior derived from a mix of accuracy and bias, which predicted changes in relationship security over time. These findings underscore the importance of perceivers' representations of their responsive behavior, both accurate and biased, as determinants of their own relationship security. PMID- 25133720 TI - Mean-level personality development across childhood and adolescence: a temporary defiance of the maturity principle and bidirectional associations with parenting. AB - In this study, we investigated mean-level personality development in children from 6 to 20 years of age. Additionally, we investigated longitudinal, bidirectional associations between child personality and maternal overreactive and warm parenting. In this 5-wave study, mothers reported on their child's personality from Time 1 (T1) through Time 4 (T4), and children provided self reports from Time 2 (T2) through Time 5 (T5). Mothers reported on their levels of overreactive and warm parenting from T2 through T4. Using cohort-sequential latent growth curve modeling, we investigated mother reported child personality from 6 to 17 years of age and child reported personality from 9 to 20 years of age. Extraversion decreased linearly across the entire study. Benevolence and conscientiousness increased from middle to late childhood, temporarily declined from late childhood to mid-adolescence, and increased again thereafter. Imagination decreased from middle childhood to mid-adolescence and also increased thereafter. Mothers reported a temporary decline in emotional stability with an increase thereafter, whereas children did not. Boys and girls differed in mean levels of the personality dimensions and, to a lesser extent, in the degree and direction of changes. Latent difference score modeling showed that child personality predicted changes in parenting and that, to a lesser extent, parenting predicted changes in child traits. Additionally, changes in child personality were associated with changes in maternal parenting. Results of the present study show that personality change is not directed at increasing maturity from childhood to mid-adolescence and that it elicits and is shaped by both positive and negative parenting. PMID- 25133721 TI - How group-based emotions are shaped by collective emotions: evidence for emotional transfer and emotional burden. AB - Extensive research has established the pivotal role that group-based emotions play in shaping intergroup processes. The underlying implicit assumption in previous work has been that these emotions reflect what the rest of the group feels (i.e., collective emotions). However, one can experience an emotion in the name of her or his group, which is inconsistent with what the collective feels. The current research investigated this phenomenon of emotional nonconformity. Particularly, we proposed that when a certain emotional reaction is perceived as appropriate, but the collective is perceived as not experiencing this emotion, people would experience stronger levels of group-based emotion, placing their emotional experience farther away from that of the collective. We provided evidence for this process across 2 different emotions: group-based guilt and group-based anger (Studies 1 and 2) and across different intergroup contexts (Israeli-Palestinian relations in Israel, and Black-White relations in the United States). In Studies 3 and 4, we demonstrate that this process is moderated by the perceived appropriateness of the collective emotional response. Studies 4 and 5 further provided evidence for the mechanisms underlying this effect, pointing to a process of emotional burden (i.e., feeling responsible for carrying the emotion in the name of the group) and of emotional transfer (i.e., transferring negative feelings one has toward the ingroup, toward the event itself). This work brings to light processes that were yet to be studied regarding the relationship between group members, their perception of their group, and the emotional processes that connect them. PMID- 25133722 TI - Evidence for the social role theory of stereotype content: observations of groups' roles shape stereotypes. AB - In applying social role theory to account for the content of a wide range of stereotypes, this research tests the proposition that observations of groups' roles determine stereotype content (Eagly & Wood, 2012). In a novel test of how stereotypes can develop from observations, preliminary research collected participants' beliefs about the occupational roles (e.g., lawyer, teacher, fast food worker, chief executive officer, store clerk, manager) in which members of social groups (e.g., Black women, Hispanics, White men, the rich, senior citizens, high school dropouts) are overrepresented relative to their numbers in the general population. These beliefs about groups' typical occupational roles proved to be generally accurate when evaluated in relation to data from the Bureau of Labor Statistics. Then, correlational studies predicted participants' stereotypes of social groups from the attributes ascribed to group members' typical occupational roles (Studies 1a, 1b, and 1c), the behaviors associated with those roles (Study 2), and the occupational interest profile of the roles (Study 3). As predicted by social role theory, beliefs about the attributes of groups' typical roles were strongly related to group stereotypes on both communion and agency/competence. In addition, an experimental study (Study 4) demonstrated that when social groups were described with changes to their typical social roles in the future, their projected stereotypes were more influenced by these future roles than by their current group stereotypes, thus supporting social role theory's predictions about stereotype change. Discussion considers the implications of these findings for stereotype change and the relation of social role theory to other theories of stereotype content. PMID- 25133723 TI - Selfish or selfless? On the signal value of emotion in altruistic behavior. AB - Theories that reject the existence of altruism presume that emotional benefits serve as ulterior motives for doing good deeds. These theories argue that even in the absence of material and reputational benefits, individuals reap utility from the feelings associated with doing good. In response to this normative view of altruism, this article examines the descriptive question of whether laypeople penalize emotional prosocial actors. Six studies find that emotion serves as a positive signal of moral character, despite the intrapsychic benefits associated with it. This is true when emotion motivates prosocial behavior (Studies 1, 2, 3, and 5) and when emotion is a positive outcome of prosocial behavior (i.e., "warm glow"; Studies 4, 5, and 6). Emotional actors are considered to be moral because people believe emotion provides an honest and direct signal that the actor feels a genuine concern for others. Consequently, prosocial actors who are motivated by the expectation of emotional rewards are judged differently than prosocial actors who are motivated by other benefits, such as reputational or material rewards (Study 6). These results suggest that laypeople do not view altruism as incompatible with all benefits to the self. PMID- 25133725 TI - Religious magnanimity: reminding people of their religious belief system reduces hostility after threat. AB - The present research tested the hypothesis that many people's ambient religious beliefs are non-hostile and magnanimous by assessing whether reminding people of their religious belief systems would reduce hostility after threat. Across religious affiliations, participants reported that their religious belief systems encourage magnanimous behavior. In addition, priming their religious belief systems caused them to act more magnanimously, but only when motivated to adhere to salient ideals (i.e., after threats; see Gailliot, Stillman, Schmeichel, Maner, & Plant, 2008; Jonas et al., 2008). Specifically, in Studies 1-5, we found that a general religious belief system prime ("Which religious belief system do you identify with?") reduced the hostility of people's thoughts, behaviors, and judgments following threat. In Studies 6 and 7, we found that the religious belief system prime only reduced hostile reactions to threat among participants who held religious beliefs that oriented them toward magnanimous ideals (Study 6) and who were dispositionally inclined to adhere to their ideals (Study 7). In Study 8, we found support for the role of magnanimous ideals by demonstrating that directly priming these ideals yielded effects similar to those produced by a religious belief system prime. These studies provide consistent evidence that, by invoking magnanimous ideals, a religious belief system prime promotes less hostile responses to threat. PMID- 25133724 TI - Paying more when paying for others. AB - Social behavior is heavily influenced by the perception of the behaviors of others. We considered how perceptions (and misperceptions) of kindness can increase generosity in economic transactions. We investigated how these perceptions can alter behavior in a novel real-life situation that pitted kindness against selfishness. That situation, consumer elective pricing, is defined by an economic transaction allowing people to purchase goods or services for any price (including zero). Field and lab experiments compared how people behave in 2 financially identical circumstances: pay-what-you-want (in which people are ostensibly paying for themselves) and pay-it-forward (in which people are ostensibly paying on behalf of someone else). In 4 field experiments, people paid more under pay-it-forward than pay-what-you-want (Studies 1-4). Four subsequent lab studies assessed whether the salience of others explains the increased payments (Study 5), whether ability to justify lowered payments (Study 6), and whether the manipulation was operating through changing the perceptions of others (Studies 7 and 8). When people rely on ambiguous perceptions, pay-it forward leads to overestimating the kindness of others and a corresponding increase in personal payment. When those perceptions are replaced with explicit descriptive norms (i.e., others' payment amounts), that effect is eliminated. Finally, subsequent studies confirmed that the effects were not driven by participant confusion (Studies 9A and 9B) and not limited by the specificity of the referent other in the pay-it-forward framing (Study 9C). PMID- 25133726 TI - The involuntary excluder effect: those included by an excluder are seen as exclusive themselves. AB - People are highly vigilant for and alarmed by social exclusion. Previous research has focused largely on the emotional and motivational consequences of being unambiguously excluded by others. The present research instead examines how people make sense of a more ambiguous dynamic, 1-person exclusion--situations in which one person (the excluder) excludes someone (the rejected) while including someone else (the included). Using different methodological paradigms, converging outcome measures, and complementary comparison standards, 5 studies present evidence of an involuntary excluder effect: Social perceivers are quick to see included persons as though they are excluders themselves. Included individuals are seen as belonging to an exclusive alliance with the excluder, as liking the excluder more than the rejected, and as likely to perpetuate future exclusion against the rejected. Behavioral evidence reinforced these findings: The included was approached with caution and suspicion. Notably, such perceptions of the included as an excluder were drawn by the rejected themselves and outside observers alike, did not reflect the attitudes and intentions of included persons or those who simulated 1-person exclusion from the vantage point of the included, applied specifically to the included (but not someone who simply witnessed the rejected's rejection), and arose as a consequence of intentional acts of exclusion (and thus, not just because 2 individuals shared an exclusive experience). Consistencies with and contributions to literatures on balance theory, minimal groups, group entitativity, and the ostracism detection system literatures are discussed. PMID- 25133727 TI - Addressing the empathy deficit: beliefs about the malleability of empathy predict effortful responses when empathy is challenging. AB - Empathy is often thought to occur automatically. Yet, empathy frequently breaks down when it is difficult or distressing to relate to people in need, suggesting that empathy is often not felt reflexively. Indeed, the United States as a whole is said to be displaying an empathy deficit. When and why does empathy break down, and what predicts whether people will exert effort to experience empathy in challenging contexts? Across 7 studies, we found that people who held a malleable mindset about empathy (believing empathy can be developed) expended greater empathic effort in challenging contexts than did people who held a fixed theory (believing empathy cannot be developed). Specifically, a malleable theory of empathy--whether measured or experimentally induced--promoted (a) more self reported effort to feel empathy when it is challenging (Study 1); (b) more empathically effortful responses to a person with conflicting views on personally important sociopolitical issues (Studies 2-4); (c) more time spent listening to the emotional personal story of a racial outgroup member (Study 5); and (d) greater willingness to help cancer patients in effortful, face-to-face ways (Study 6). Study 7 revealed a possible reason for this greater empathic effort in challenging contexts: a stronger interest in improving one's empathy. Together, these data suggest that people's mindsets powerfully affect whether they exert effort to empathize when it is needed most, and these data may represent a point of leverage in increasing empathic behaviors on a broad scale. PMID- 25133728 TI - The psychology of martyrdom: making the ultimate sacrifice in the name of a cause. AB - Martyrdom is defined as the psychological readiness to suffer and sacrifice one's life for a cause. An integrative set of 8 studies investigated the concept of martyrdom by creating a new tool to quantitatively assess individuals' propensity toward self-sacrifice. Studies 1A-1C consisted of psychometric work attesting to the scale's unidimensionality, internal consistency, and temporal stability while examining its nomological network. Studies 2A-2B focused on the scale's predictive validity, especially as it relates to extreme behaviors and suicidal terrorism. Studies 3-5 focused on the influence of self-sacrifice on automatic decision making, costly and altruistic behaviors, and morality judgments. Results involving more than 2,900 participants from different populations, including a terrorist sample, supported the proposed conceptualization of martyrdom and demonstrated its importance for a vast repertoire of cognitive, emotional, and behavioral phenomena. Implications and future directions for the psychology of terrorism are discussed. PMID- 25133729 TI - You are so beautiful... to me: seeing beyond biases and achieving accuracy in romantic relationships. AB - Do romantic partners see each other realistically, or do they have overly positive perceptions of each other? Research has shown that realism and positivity co-exist in romantic partners' perceptions (Boyes & Fletcher, 2007). The current study takes a novel approach to explaining this seemingly paradoxical effect when it comes to physical attractiveness--a highly evaluative trait that is especially relevant to romantic relationships. Specifically, we argue that people are aware that others do not see their partners as positively as they do. Using both mean differences and correlational approaches, we test the hypothesis that despite their own biased and idiosyncratic perceptions, people have 2 types of partner-knowledge: insight into how their partners see themselves (i.e., identity accuracy) and insight into how others see their partners (i.e., reputation accuracy). Our results suggest that romantic partners have some awareness of each other's identity and reputation for physical attractiveness, supporting theories that couple members' perceptions are driven by motives to fulfill both esteem- and epistemic-related needs (i.e., to see their partners positively and realistically). PMID- 25133730 TI - On the consistency of personality types across adulthood: latent profile analyses in two large-scale panel studies. AB - Consistency and change in personality were analyzed by examining personality types across adulthood and old age using data from 2 nationally representative panel studies from Germany (N = 14,718; 16-82 years) and Australia (N = 8,315; 15 79 years). In both samples, the Big Five personality traits were measured twice across a period of 4 years. Latent profile analyses and latent profile transition analyses revealed 4 main findings: First, solutions with 3 (in the German sample) or 4 (in the Australian sample) personality types were found to be most interpretable. Second, measurement invariance tests revealed that these personality types were consistent across all age groups but differed slightly between men and women. Third, age was related to the number of individuals classified within each personality type. Namely, there were more resilients and fewer undercontrollers in older compared with younger age groups. Fourth, there was strong consistency of personality type membership across a period of 4 years in both genders and most age cohorts. Comparatively less consistency across time was found for undercontrollers and individuals in old age. Taken together, these findings show that in the 2 nations studied here, personality types were highly consistent across gender, age, and time. PMID- 25133731 TI - A general synthesis of ynones from aldehydes via oxidative C-C bond cleavage under aerobic conditions. AB - We describe a direct synthesis of various ynones from readily available aldehydes and hypervalent alkynyl iodides. In this method, a gold catalyst and a secondary amine work synergistically to produce the trisubstituted allenyl aldehyde, which can be converted to the desired ynone through an in situ C-C bond oxidative cleavage using molecular oxygen. PMID- 25133732 TI - Metabolic engineering of Saccharomyces cerevisiae for caffeine and theobromine production. AB - Caffeine (1, 3, 7-trimethylxanthine) and theobromine (3, 7-dimethylxanthine) are the major purine alkaloids in plants, e.g., tea (Camellia sinensis) and coffee (Coffea arabica). Caffeine is a major component of coffee and is used widely in food and beverage industries. Most of the enzymes involved in the caffeine biosynthetic pathway have been reported previously. Here, we demonstrated the biosynthesis of caffeine (0.38 mg/L) by co-expression of Coffea arabica xanthosine methyltransferase (CaXMT) and Camellia sinensis caffeine synthase (TCS) in Saccharomyces cerevisiae. Furthermore, we endeavored to develop this production platform for making other purine-based alkaloids. To increase the catalytic activity of TCS in an effort to increase theobromine production, we identified four amino acid residues based on structural analyses of 3D-model of TCS. Two TCS1 mutants (Val317Met and Phe217Trp) slightly increased in theobromine accumulation and simultaneously decreased in caffeine production. The application and further optimization of this biosynthetic platform are discussed. PMID- 25133733 TI - Deprived TLR9 expression in apparently healthy nasal mucosa might trigger polyp growth in chronic rhinosinusitis patients. AB - BACKGROUND: The origin of nasal polyps in chronic rhinosinusitis is unknown, but the role of viral infections in polyp growth is clinically well established. Toll like receptors (TLRs) have recently emerged as key players in our local airway defense against microbes. Among these, TLR9 has gained special interest in viral diseases. Many studies on chronic rhinosinusitis with nasal polyps (CRSwNP) compare polyp tissue with nasal mucosa from polyp-free individuals. Knowledge about changes in the turbinate tissue bordering the polyp tissue is limited. OBJECTIVES: To analyse the role of TLR9 mediated microbial defense in tissue bordering the polyp. METHODS: Nasal polyps and turbinate tissue from 11 patients with CRSwNP and turbinate tissue from 11 healthy controls in total were used. Five biopsies from either group were analysed immediately with flow cytometry regarding receptor expression and 6 biopsies were used for in vitro stimulation with a TLR9 agonist, CpG. Cytokine release was analysed using Luminex. Eight patients with CRSwNP in total were intranasally challenged with CpG/placebo 24 hours before surgery and the biopsies were collected and analysed as above. RESULTS: TLR9 expression was detected on turbinate epithelial cells from healthy controls and polyp epithelial cells from patients, whereas TLR9 was absent in turbinate epithelial cells from patients. CpG stimulation increased the percentage cells expressing TLR9 and decreased percentage cells expressing VEGFR2 in turbinate tissue from patients. After CpG stimulation the elevated levels of IL-6, G-CSF and MIP-1beta in the turbinate tissue from patients were reduced towards the levels demonstrated in healthy controls. CONCLUSION: Defects in the TLR9 mediated microbial defense in the mucosa adjacent to the anatomic origin of the polyp might explain virus induced polyp growth. CpG stimulation decreased VEGFR2, suggesting a role for CpG in polyp formation. The focus on turbinate tissue in patients with CRSwNP opens new perspectives in CRSwNP-research. PMID- 25133738 TI - Elevated levels of circulating DNA in cardiovascular disease patients: metagenomic profiling of microbiome in the circulation. AB - Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An expanding body of evidence supports the role of human microbiome in the establishment of CVDs and, this has gained much attention recently. This work was aimed to study the circulating human microbiome in CVD patients and healthy subjects. The levels of circulating cell free DNA (circDNA) was higher in CVD patients (n = 80) than in healthy controls (n = 40). More specifically, the relative levels of circulating bacterial DNA and the ratio of 16S rRNA/beta globin gene copy numbers were higher in the circulation of CVD patients than healthy individuals. In addition, we found a higher circulating microbial diversity in CVD patients (n = 3) in comparison to healthy individuals (n = 3) by deep shotgun sequencing. At the phylum level, we observed a dominance of Actinobacteria in CVD patients, followed by Proteobacteria, in contrast to that in healthy controls, where Proteobacteria was predominantly enriched, followed by Actinobacteria. The circulating virome in CVD patients was enriched with bacteriophages with a preponderance of Propionibacterium phages, followed by Pseudomonas phages and Rhizobium phages in contrast to that in healthy individuals, where a relatively greater abundance of eukaryotic viruses dominated by Lymphocystis virus (LCV) and Torque Teno viruses (TTV) was observed. Thus, the release of bacterial and viral DNA elements in the circulation could play a major role leading to elevated circDNA levels in CVD patients. The increased circDNA levels could be either the cause or consequence of CVD incidence, which needs to be explored further. PMID- 25133740 TI - Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal carrier on drug delivery and treatment efficacy. AB - PURPOSE: To determine the effect of different drug-loaded nanocarriers (micelles and liposomes) on delivery and treatment efficacy for radiofrequency ablation (RFA) combined with nanodrugs. MATERIALS/METHODS: Fischer 344 rats were used (n = 196). First, single subcutaneous R3230 tumors or normal liver underwent RFA followed by immediate administration of i.v. fluorescent beads (20, 100, and 500 nm), with fluorescent intensity measured at 4-24 hr. Next, to study carrier type on drug efficiency, RFA was combined with micellar (20 nm) or liposomal (100 nm) preparations of doxorubicin (Dox; targeting HIF-1alpha) or quercetin (Qu; targeting HSP70). Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg i.v., 15 min post-RFA), and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min post-RFA (0.3 mg i.v.). Tumor coagulation and HIF-1alpha or HSP70 expression were assessed 24 hr post-RFA. Third, the effect of RFA combined with i.v. Lipo-Dox, Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA) compared to RFA alone on tumor growth and animal endpoint survival was evaluated. Finally, drug uptake was compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4-72 hr. RESULTS: Smaller 20 nm beads had greater deposition and deeper tissue penetration in both tumor (100 nm/500 nm) and liver (100 nm) (p<0.05). Mic-Dox and Mic-Qu suppressed periablational HIF-1alpha or HSP70 rim thickness more than liposomal preparations (p<0.05). RFA/Mic-Dox had greater early (4 hr) intratumoral doxorubicin, but RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24-72 hr post RFA (p<0.04). No difference in tumor growth and survival was seen between RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint survival compared to RFA/Mic-Dox (p<0.03). CONCLUSION: With RF ablation, smaller particle micelles have superior penetration and more effective local molecular modulation. However, larger long-circulating liposomal carriers can result in greater intratumoral drug accumulation over time and reduced tumor growth. Accordingly, different carriers provide specific advantages, which should be considered when formulating optimal combination therapies. PMID- 25133742 TI - Prediction of chemical biodegradability using support vector classifier optimized with differential evolution. AB - Reliable computer models for the prediction of chemical biodegradability from molecular descriptors and fingerprints are very important for making health and environmental decisions. Coupling of the differential evolution (DE) algorithm with the support vector classifier (SVC) in order to optimize the main parameters of the classifier resulted in an improved classifier called the DE-SVC, which is introduced in this paper for use in chemical biodegradability studies. The DE-SVC was applied to predict the biodegradation of chemicals on the basis of extensive sample data sets and known structural features of molecules. Our optimization experiments showed that DE can efficiently find the proper parameters of the SVC. The resulting classifier possesses strong robustness and reliability compared with grid search, genetic algorithm, and particle swarm optimization methods. The classification experiments conducted here showed that the DE-SVC exhibits better classification performance than models previously used for such studies. It is a more effective and efficient prediction model for chemical biodegradability. PMID- 25133741 TI - Mice in Bion-M 1 space mission: training and selection. AB - After a 16-year hiatus, Russia has resumed its program of biomedical research in space, with the successful 30-day flight of the Bion-M 1 biosatellite (April 19 May 19, 2013). The principal species for biomedical research in this project was the mouse. This paper presents an overview of the scientific goals, the experimental design and the mouse training/selection program. The aim of mice experiments in the Bion-M 1 project was to elucidate cellular and molecular mechanisms, underlying the adaptation of key physiological systems to long-term exposure in microgravity. The studies with mice combined in vivo measurements, both in flight and post-flight (including continuous blood pressure measurement), with extensive in vitro studies carried out shortly after return of the mice and in the end of recovery study. Male C57/BL6 mice group housed in space habitats were flown aboard the Bion-M 1 biosatellite, or remained on ground in the control experiment that replicated environmental and housing conditions in the spacecraft. Vivarium control groups were used to account for housing effects and possible seasonal differences. Mice training included the co-adaptation in housing groups and mice adaptation to paste food diet. The measures taken to co adapt aggressive male mice in housing groups and the peculiarities of "space" paste food are described. The training program for mice designated for in vivo studies was broader and included behavioral/functional test battery and continuous behavioral measurements in the home-cage. The results of the preliminary tests were used for the selection of homogenous groups. After the flight, mice were in good condition for biomedical studies and displayed signs of pronounced disadaptation to Earth's gravity. The outcomes of the training program for the mice welfare are discussed. We conclude that our training program was effective and that male mice can be successfully employed in space biomedical research. PMID- 25133743 TI - Hyperspectral reflected light microscopy of plasmonic Au/Ag alloy nanoparticles incubated as multiplex chromatic biomarkers with cancer cells. AB - A hyperspectral microscopy system based on a reflected light method for plasmonic nanoparticle (NP) imaging was designed and compared with a conventional darkfield method for spatial localization and spectroscopic identification of single Au, Ag and Au/Ag alloy NPs incubated with fixed human cancer cell preparations. A new synthesis protocol based on co-reduction of Au and Ag salts combined with the seeded growth technique was used for the fabrication of monodispersed alloy NPs with sizes ranging from 30 to 100 nm in diameter. We validated theoretically and experimentally the performance of 60 nm Au, Ag and Au/Ag (50 : 50) NPs as multiplexed biological chromatic markers for biomedical diagnostics and optical biosensing. The advantages of the proposed reflected light microscopy method are presented for NP imaging in a complex and highly diffusing medium such as a cellular environment. The obtained information is essential for the development of a high throughput, selective and efficient strategy for cancer detection and treatment. PMID- 25133744 TI - Nonstoichiometric perovskite CaMnO(3-delta) for oxygen electrocatalysis with high activity. AB - Perovskite oxides offer efficient and cheap electrocatalysts for both oxygen reduction reactions and oxygen evolution reactions (ORR/OER) in diverse oxygen based electrochemical technologies. In this study, we report a facile strategy to enhance the electrocatalytic activity of CaMnO3 by introducing oxygen defects. The nonstoichiometric CaMnO(3-delta) (0 < delta <= 0.5) was prepared through thermal reduction of pristine perovskite microspheres and nanoparticles, which were synthesized from thermal-decomposition of carbonate precursors and the Pechini route, respectively. The as-prepared samples were analyzed by chemical titration, structural refinement, thermogravimetric analysis, and energy spectrometry. In 0.1 M KOH aqueous solution, the nonstoichiometric CaMnO(3-delta) with delta near 0.25 and an average Mn valence close to 3.5 exhibited the highest ORR activity (36.7 A g(-1) at 0.70 V vs RHE, with onset potential of 0.96 V), which is comparable to that of benchmark Pt/C. Density functional theory (DFT) studies and electrical conductivity measurement revealed that the enhanced ORR kinetics is due to facilitated oxygen activation and improved electrical properties. Besides high activity, the nonstoichiometric perovskite oxides showed respectable catalytic stability. Furthermore, the moderate oxygen-defective CaMnO(3-delta) (delta ~ 0.25) favored the OER because of the improved electrical conductivity. This study makes nonstoichiometric CaMnO(3-delta) a promising active, inexpensive bifunctional catalytic material for reversible ORR and OER. PMID- 25133745 TI - A highly selective sulfinate ester probe for thiol bioimaging. AB - We describe here hitherto unexplored chemistry of the sulfinate ester functional group as being highly selective towards nucleophilic substitution by thiols at physiological pH. Using this cleavable trigger, an optical thiol probe that is suitable for thiol bioimaging has been developed. PMID- 25133746 TI - Cancer screening rates in individuals with different life expectancies. AB - IMPORTANCE: Routine cancer screening has unproven net benefit for patients with limited life expectancy. OBJECTIVE: To examine the patterns of prostate, breast, cervical, and colorectal cancer screening in the United States in individuals with different life expectancies. DESIGN, SETTING, AND PARTICIPANTS: Data from the population-based National Health Interview Survey (NHIS) from 2000 through 2010 were used and included 27 404 participants aged 65 years or older. Using a validated mortality index specific for NHIS, participants were grouped into those with low (<25%), intermediate (25%-49%), high (50%-74%), and very high (>=75%) risks of 9-year mortality. MAIN OUTCOMES AND MEASURES: Rates of prostate, breast, cervical, and colorectal cancer screening. RESULTS: In participants with very high mortality risk, 31% to 55% received recent cancer screening, with prostate cancer screening being most common (55%). For women who had a hysterectomy for benign reasons, 34% to 56% had a Papanicolaou test within the past 3 years. On multivariate analysis, very high vs low mortality risk was associated with less screening for prostate (odds ratio [OR], 0.65 [95% CI, 0.50-0.85]), breast (OR, 0.43 [95% CI, 0.35-0.53]), and cervical (OR, 0.50 [95% CI, 0.36-0.70]) cancers. There was less screening for prostate and cervical cancers in more recent years compared with 2000, and there was no significant interaction between calendar year and mortality risk for any cancer screening (P > .05 for all cancers). Our sensitivity analysis showed that screening was also common in individuals with less than 5-year life expectancy. CONCLUSIONS AND RELEVANCE: A substantial proportion of the US population with limited life expectancy received prostate, breast, cervical, and colorectal cancer screening that is unlikely to provide net benefit. These results suggest that overscreening is common in both men and women, which not only increases health care expenditure but can lead to net patient harm. PMID- 25133747 TI - Genome-wide prediction of the polymorphic Ser gene family in Tetrahymena thermophila based on motif analysis. AB - Even though antigenic variation is employed among parasitic protozoa for host immune evasion, Tetrahymena thermophila, a free-living ciliate, can also change its surface protein antigens. These cysteine-rich glycosylphosphatidylinositol (GPI)-linked surface proteins are encoded by a family of polymorphic Ser genes. Despite the availability of T. thermophila genome, a comprehensive analysis of the Ser family is limited by its high degree of polymorphism. In order to overcome this problem, a new approach was adopted by searching for Ser candidates with common motif sequences, namely length-specific repetitive cysteine pattern and GPI anchor site. The candidate genes were phylogenetically compared with the previously identified Ser genes and classified into subtypes. Ser candidates were often found to be located as tandem arrays of the same subtypes on several chromosomal scaffolds. Certain Ser candidates located in the same chromosomal arrays were transcriptionally expressed at specific T. thermophila developmental stages. These Ser candidates selected by the motif analysis approach can form the foundation for a systematic identification of the entire Ser gene family, which will contribute to the understanding of their function and the basis of T. thermophila antigenic variation. PMID- 25133748 TI - Effect of sodium chloride on hydration structures of PMEA and P(MPC-r-BMA). AB - The hydration structures of two different types of biomaterials, i.e., poly(2 methoxyethyl acrylate) (PMEA) and a random copolymer of 2-methacryloyloxyethyl phosphorylcholine and n-butyl methacrylate (P(MPC-r-BMA)), were investigated by means of attenuated total reflection infrared (ATR-IR) spectroscopy. The effects of the addition of sodium chloride to liquid water in contact with the surfaces of the polymer films were examined. The neutral polymer of PMEA was easily dehydrated by NaCl addition, whereas the zwitterionic polymer of P(MPC-r-BMA) was hardly dehydrated. More specifically, nonfreezing water having a strong interaction with the PMEA chain and freezing bound water having an intermediate interaction were hardly dehydrated by contacting with normal saline solution, whereas freezing water having a weak interaction with the PMEA chain was readily dehydrated. In contrast, freezing water in P(MPC-r-BMA) is exchanged for the saline solution contacting with the material surface without dehydration. PMID- 25133749 TI - Long-term disease dynamics for a specialized parasite of ant societies: a field study. AB - Many studies have investigated how social insects behave when a parasite is introduced into their colonies. These studies have been conducted in the laboratory, and we still have a limited understanding of the dynamics of ant parasite interactions under natural conditions. Here we consider a specialized parasite of ant societies (Ophiocordyceps camponoti-rufipedis infecting Camponotus rufipes) within a rainforest. We first established that the parasite is unable to develop to transmission stage when introduced within the host nest. Secondly, we surveyed all colonies in the studied area and recorded 100% prevalence at the colony level (all colonies were infected). Finally, we conducted a long-term detailed census of parasite pressure, by mapping the position of infected dead ants and foraging trails (future hosts) in the immediate vicinity of the colonies over 20 months. We report new dead infected ants for all the months we conducted the census--at an average of 14.5 cadavers/month/colony. Based on the low infection rate, the absence of colony collapse or complete recovery of the colonies, we suggest that this parasite represents a chronic infection in the ant societies. We also proposed a "terminal host model of transmission" that links the age-related polyethism to the persistence of a parasitic infection. PMID- 25133750 TI - Activity Patterns of Preschool-Aged Children at Risk for Obesity. AB - BACKGROUND: Although the prevalence of obesity in young children highlights the importance of early interventions to promote physical activity (PA), there are limited data on activity patterns in this age group. The purpose of this study was to describe activity patterns in preschool-aged children and explore differences by weight status. METHODS: Analyses use baseline data from Healthy Homes/Healthy Kids-Preschool, a pilot obesity prevention trial of preschool-aged children who are overweight or at risk for being overweight. A modified parent reported version of the previous-day PA recall was used to summarize types of activity. Accelerometry was used to summarize daily and hourly activity patterns. RESULTS: "Playing with toys" accounted for the largest proportion of a child's previous day, followed by "meals and snacks" and "chores." Accelerometry-measured daily time spent in sedentary behavior, light PA, and moderate-to-vigorous PA (MVPA) was 412, 247, and 69 minutes, respectively. Percentage of hourly time spent in MVPA ranged from 3% to 13%, peaking in the late morning and evening hours. There were no statistically significant MVPA differences by weight status. CONCLUSIONS: This study extends our understanding of activity types, amounts, and patterns in preschool-aged children and warrants further exploration of differences in PA patterns by weight status. PMID- 25133751 TI - Mutation screening of retinal dystrophy patients by targeted capture from tagged pooled DNAs and next generation sequencing. AB - PURPOSE: Retinal dystrophies are genetically heterogeneous, resulting from mutations in over 200 genes. Prior to the development of massively parallel sequencing, comprehensive genetic screening was unobtainable for most patients. Identifying the causative genetic mutation facilitates genetic counselling, carrier testing and prenatal/pre-implantation diagnosis, and often leads to a clearer prognosis. In addition, in a proportion of cases, when the mutation is known treatment can be optimised and patients are eligible for enrolment into clinical trials for gene-specific therapies. METHODS: Patient genomic DNA was sheared, tagged and pooled in batches of four samples, prior to targeted capture and next generation sequencing. The enrichment reagent was designed against genes listed on the RetNet database (July 2010). Sequence data were aligned to the human genome and variants were filtered to identify potential pathogenic mutations. These were confirmed by Sanger sequencing. RESULTS: Molecular analysis of 20 DNAs from retinal dystrophy patients identified likely pathogenic mutations in 12 cases, many of them known and/or confirmed by segregation. These included previously described mutations in ABCA4 (c.6088C>T,p.R2030*; c.5882G>A,p.G1961E), BBS2 (c.1895G>C,p.R632P), GUCY2D (c.2512C>T,p.R838C), PROM1 (c.1117C>T,p.R373C), RDH12 (c.601T>C,p.C201R; c.506G>A,p.R169Q), RPGRIP1 (c.3565C>T,p.R1189*) and SPATA7 (c.253C>T,p.R85*) and new mutations in ABCA4 (c.3328+1G>C), CRB1 (c.2832_2842+23del), RP2 (c.884-1G>T) and USH2A (c.12874A>G,p.N4292D). CONCLUSIONS: Tagging and pooling DNA prior to targeted capture of known retinal dystrophy genes identified mutations in 60% of cases. This relatively high success rate may reflect enrichment for consanguineous cases in the local Yorkshire population, and the use of multiplex families. Nevertheless this is a promising high throughput approach to retinal dystrophy diagnostics. PMID- 25133752 TI - Relative accuracy evaluation. AB - The quality of data plays an important role in business analysis and decision making, and data accuracy is an important aspect in data quality. Thus one necessary task for data quality management is to evaluate the accuracy of the data. And in order to solve the problem that the accuracy of the whole data set is low while a useful part may be high, it is also necessary to evaluate the accuracy of the query results, called relative accuracy. However, as far as we know, neither measure nor effective methods for the accuracy evaluation methods are proposed. Motivated by this, for relative accuracy evaluation, we propose a systematic method. We design a relative accuracy evaluation framework for relational databases based on a new metric to measure the accuracy using statistics. We apply the methods to evaluate the precision and recall of basic queries, which show the result's relative accuracy. We also propose the method to handle data update and to improve accuracy evaluation using functional dependencies. Extensive experimental results show the effectiveness and efficiency of our proposed framework and algorithms. PMID- 25133753 TI - Adaptive properties of human cementum and cementum dentin junction with age. AB - OBJECTIVES: The objective of this study was to evaluate age related changes in physical (structure/mechanical properties) and chemical (elemental/inorganic mineral content) properties of cementum layers interfacing dentin. METHODS: Human mandibular molars (N=43) were collected and sorted by age (younger=19-39, middle=40-60, older=61-81 years). The structures of primary and secondary cementum (PC, SC) types were evaluated using light and atomic force microscopy (AFM) techniques. Chemical composition of cementum layers were characterized through gravimetric analysis by estimating ash weight and concentrations of Ca, Mn, and Zn trace elements in the analytes through inductively coupled plasma mass spectroscopy. The hardness of PC and SC was determined using microindentation and site-specific reduced elastic modulus properties were determined using nanoindentation techniques. RESULTS: PC contained fibrous 1-3 um wide hygroscopic radial PDL-inserts. SC illustrated PC-like structure adjacent to a multilayered architecture composing of regions that contained mineral dominant lamellae. The width of the cementum dentin junction (CDJ) decreased as measured from the cementum enamel junction (CEJ) to the tooth apex (49-21 um), and significantly decreased with age (44-23 um; p<0.05). The inorganic ratio defined as the ratio of post-burn to pre-burn weight increased with age within primary cementum (PC) and secondary cementum (SC). Cementum showed an increase in hardness with age (PC (0.40-0.46 GPa), SC (0.37-0.43 GPa)), while dentin showed a decreasing trend (coronal dentin (0.70-0.72 GPa); apical dentin (0.63-0.73 GPa)). SIGNIFICANCE: The observed physicochemical changes are indicative of increased mineralization of cementum and CDJ over time. Changes in tissue properties of teeth can alter overall tooth biomechanics and in turn the entire bone-tooth complex including the periodontal ligament. This study provides baseline information about the changes in physicochemical properties of cementum with age, which can be identified as adaptive in nature. PMID- 25133754 TI - Parenting and the Family Check-Up: Changes in Observed Parent-Child Interaction Following Early Childhood Intervention. AB - Coercion theory posits a cyclical relationship between harsh and coercive parent child interactions and problem behavior beginning in early childhood. As coercive interactions have been theorized and found to facilitate the development and growth of early conduct problems, early interventions often target parenting to prevent or reduce early disruptive problem behavior. This study utilizes direct observations of parent-child interactions from the Early Steps Multisite study (N = 731; 369 boys) to examine the effect of the Family Check-Up, a family-centered intervention program, on measures of parent-child positive engagement and coercion from age 2 through 5, as well as on childhood problem behavior at age 5. Results indicate that high levels of parent-child positive engagement were associated with less parent-child coercion the following year, but dyadic coercion was unrelated to future levels of positive engagement. In addition, families assigned to the Family Check-Up showed increased levels of positive engagement at ages 3 and 5, and the association between positive engagement at age 3 and child problem behavior at age 5 was mediated by reductions in parent child coercion at age 4. These findings provide longitudinal confirmation that increasing positive engagement in parent-child interaction can reduce the likelihood of coercive family dynamics in early childhood and growth in problem behavior. PMID- 25133756 TI - Restoration as mitigation: analysis of stream mitigation for coal mining impacts in southern Appalachia. AB - Compensatory mitigation is commonly used to replace aquatic natural resources being lost or degraded but little is known about the success of stream mitigation. This article presents a synthesis of information about 434 stream mitigation projects from 117 permits for surface mining in Appalachia. Data from annual monitoring reports indicate that the ratio of lengths of stream impacted to lengths of stream mitigation projects were <1 for many projects, and most mitigation was implemented on perennial streams while most impacts were to ephemeral and intermittent streams. Regulatory requirements for assessing project outcome were minimal; visual assessments were the most common and 97% of the projects reported suboptimal or marginal habitat even after 5 years of monitoring. Less than a third of the projects provided biotic or chemical data; most of these were impaired with biotic indices below state standards and stream conductivity exceeding federal water quality criteria. Levels of selenium known to impair aquatic life were reported in 7 of the 11 projects that provided Se data. Overall, the data show that mitigation efforts being implemented in southern Appalachia for coal mining are not meeting the objectives of the Clean Water Act to replace lost or degraded streams ecosystems and their functions. PMID- 25133755 TI - Nutritional status in community-dwelling elderly in France in urban and rural areas. AB - Malnutrition is a frequent condition in elderly people, especially in nursing homes and geriatric wards. Its frequency is less well known among elderly living at home. The objective of this study was to describe the nutritional status evaluated by the Mini Nutritional Assessment (MNA) of elderly community-dwellers living in rural and urban areas in France and to investigate its associated factors. METHODS: Subjects aged 65 years and over from the Approche Multidisciplinaire Integree (AMI) cohort (692 subjects living in a rural area) and the Three-City (3C) cohort (8,691 subjects living in three large urban zones) were included. A proxy version of the MNA was reconstructed using available data from the AMI cohort. Sensitivity and specificity were used to evaluate the agreement between the proxy version and the standard version in AMI. The proxy MNA was computed in both cohorts to evaluate the frequency of poor nutritional status. Factors associated with this state were investigated in each cohort separately. RESULTS: In the rural sample, 38.0% were females and the mean age was 75.5 years. In the urban sample, 60.3% were females and the mean age was 74.1 years. Among subjects in living in the rural sample, 7.4% were in poor nutritional status while the proportion was 18.5% in the urban sample. Female gender, older age, being widowed, a low educational level, low income, low body mass index, being demented, having a depressive symptomatology, a loss of autonomy and an intake of more than 3 drugs appeared to be independently associated with poor nutritional status. CONCLUSION: Poor nutritional status was commonly observed among elderly people living at home in both rural and urban areas. The associated factors should be further considered for targeting particularly vulnerable individuals. PMID- 25133757 TI - Evaluating landscape options for corridor restoration between giant panda reserves. AB - The establishment of corridors can offset the negative effects of habitat fragmentation by connecting isolated habitat patches. However, the practical value of corridor planning is minimal if corridor identification is not based on reliable quantitative information about species-environment relationships. An example of this need for quantitative information is planning for giant panda conservation. Although the species has been the focus of intense conservation efforts for decades, most corridor projects remain hypothetical due to the lack of reliable quantitative researches at an appropriate spatial scale. In this paper, we evaluated a framework for giant panda forest corridor planning. We linked our field survey data with satellite imagery, and conducted species occupancy modelling to examine the habitat use of giant panda within the potential corridor area. We then conducted least-cost and circuit models to identify potential paths of dispersal across the landscape, and compared the predicted cost under current conditions and alternative conservation management options considered during corridor planning. We found that due to giant panda's association with areas of low elevation and flat terrain, human infrastructures in the same area have resulted in corridor fragmentation. We then identified areas with high potential to function as movement corridors, and our analysis of alternative conservation scenarios showed that both forest/bamboo restoration and automobile tunnel construction would significantly improve the effectiveness of corridor, while residence relocation would not significantly improve corridor effectiveness in comparison with the current condition. The framework has general value in any conservation activities that anticipate improving habitat connectivity in human modified landscapes. Specifically, our study suggested that, in this landscape, automobile tunnels are the best means to remove current barriers to giant panda movements caused by anthropogenic interferences. PMID- 25133758 TI - Microretroreflector-sedimentation immunoassays for pathogen detection. AB - Point-of-care detection of pathogens is medically valuable but poses challenging trade-offs between instrument complexity and clinical and analytical sensitivity. Here we introduce a diagnostic platform utilizing lithographically fabricated micron-scale forms of cubic retroreflectors, arguably one of the most optically detectable human artifacts, as reporter labels for use in sensitive immunoassays. We demonstrate the applicability of this novel optical label in a simple assay format in which retroreflector cubes are first mixed with the sample. The cubes are then allowed to settle onto an immuno-capture surface, followed by inversion for gravity-driven removal of nonspecifically bound cubes. Cubes bridged to the capture surface by the analyte are detected using inexpensive, low-numerical aperture optics. For model bacterial and viral pathogens, sensitivity in 10% human serum was found to be 10(4) bacterial cells/mL and 10(4) virus particles/mL, consistent with clinical utility. PMID- 25133759 TI - Association of poor subjective sleep quality with risk for death by suicide during a 10-year period: a longitudinal, population-based study of late life. AB - IMPORTANCE: Older adults have high rates of sleep disturbance, die by suicide at disproportionately higher rates compared with other age groups, and tend to visit their physician in the weeks preceding suicide death. To our knowledge, to date, no study has examined disturbed sleep as an independent risk factor for late-life suicide. OBJECTIVE: To examine the relative independent risk for suicide associated with poor subjective sleep quality in a population-based study of older adults during a 10-year observation period. DESIGN, SETTING, AND PARTICIPANTS: A longitudinal case-control cohort study of late-life suicide among a multisite, population-based community sample of older adults participating in the Established Populations for Epidemiologic Studies of the Elderly. Of 14 456 community older adults sampled, 400 control subjects were matched (on age, sex, and study site) to 20 suicide decedents. MAIN OUTCOMES AND MEASURES: Primary measures included the Sleep Quality Index, the Center for Epidemiologic Studies Depression Scale, and vital statistics. RESULTS: Hierarchical logistic regressions revealed that poor sleep quality at baseline was significantly associated with increased risk for suicide (odds ratio [OR], 1.39; 95% CI, 1.14 1.69; P < .001) by 10 follow-up years. In addition, 2 sleep items were individually associated with elevated risk for suicide at 10-year follow-up: difficulty falling asleep (OR, 2.24; 95% CI, 1.27-3.93; P < .01) and nonrestorative sleep (OR, 2.17; 95% CI, 1.28-3.67; P < .01). Controlling for depressive symptoms, baseline self-reported sleep quality was associated with increased risk for death by suicide (OR, 1.30; 95% CI, 1.04-1.63; P < .05). CONCLUSIONS AND RELEVANCE: Our results indicate that poor subjective sleep quality is associated with increased risk for death by suicide 10 years later, even after adjustment for depressive symptoms. Disturbed sleep appears to confer considerable risk, independent of depressed mood, for the most severe suicidal behaviors and may warrant inclusion in suicide risk assessment frameworks to enhance detection of risk and intervention opportunity in late life. PMID- 25133761 TI - Multiple DNA architectures with the participation of inorganic metal ions. AB - Here we develop a synthetic protocol for assembling DNA with participating metal ions into multiple shapes. DNA molecules first form coordination complexes with metal ions and these coordination complexes become nucleation sites for primary crystals of metal inorganic salt, and then elementary units of space-filling architectures based on specific geometry form, and finally elementary units assemble into variously larger multiple architectures according to different spatial configurations. We anticipate that our strategy for self-assembling various custom architectures is applicable to most biomolecules possessing donor atoms that can form coordination complexes with metal ions. These multiple architectures provide a general platform for the engineering and assembly of advanced materials possessing features on the micrometer scale and having novel activity. PMID- 25133762 TI - Response to comment on "Mercury biomagnification through food webs is affected by physical and chemical characteristics of lakes". PMID- 25133760 TI - Left and right lung asynchrony as a physiological indicator for unilateral bronchial obstruction in interventional bronchoscopy. AB - BACKGROUND: In patients with bronchial obstruction, pulmonary function tests may not change significantly after intervention. The airflow asynchrony in both lungs due to unilateral bronchial obstruction may be applicable as a physiological indicator. The airflow asynchrony is reflected by the difference in the left and right lung sound development at tidal breathing. OBJECTIVES: To investigate the usefulness of left and right lung asynchrony due to unilateral bronchial obstruction as a physiological indicator for interventional bronchoscopy. METHODS: Fifty cases with central airway obstruction were classified into three groups: tracheal, bronchial and extensive obstruction. The gap index was defined as the absolute value of the average of gaps between the left and right lung sound intensity peaks for a 12-second duration. RESULTS: Before interventional bronchoscopy, the gap index was significantly higher in the bronchial (p<0.05) and extensive obstruction groups (p<0.05) than in the tracheal group. The gap index in cases with unilateral bronchial obstruction of at least 80% (0.18+/-0.04 seconds) was significantly higher than in cases with less than 80% obstruction (0.02+/-0.01 seconds, p<0.05). After intervention for bronchial obstruction, the dyspnea scale (p<0.001) and gap index significantly improved (p<0.05), although no significant improvements were found in spirometric assessments. The responder rates for dyspnea were 79.3% for gap indexes over 0.06 seconds and 55.6% for gap indexes of 0.06 seconds or under. CONCLUSIONS: Assessment of left and right lung asynchrony in central airway obstruction with bronchial involvement may provide useful physiological information for interventional bronchoscopy. PMID- 25133763 TI - Creating an effective campaign for change: strategies for teaching value. PMID- 25133764 TI - Single molecule DNA intercalation in continuous homogenous elongational flow. AB - Sequence-nonspecific staining of DNA with intercalating fluorophores is required for fluorescence-based length estimation of elongated DNA in optical mapping techniques. However, the observed length of a DNA molecule is affected by the relative concentrations of DNA and dye. In some applications, predetermination of DNA concentration may not be possible. Here we present a microfluidic approach in which individual DNA molecules are entrained by converging laminar sheath flows containing the intercalating dye PO-PRO-1. This provides uniform staining regardless of DNA concentration, and uniform elastic stretching of DNA in continuous elongational flow. On-chip intercalation provides a unique process for concentration-independent staining of long DNA fragments for the optical mapping method Genome Sequence Scanning (GSS), and normalizes intramolecular elasticity across a broad range of molecule lengths. These advances permit accurate mapping of observed molecules to sequence derived templates, thus improving detection of complex bacterial mixtures using GSS. PMID- 25133765 TI - Issues in online patient self-reporting of health status. AB - Patient self-reporting of symptoms and quality of life following surgical interventions is generally delivered in the form of paper-based questionnaires to be completed in the outpatient clinic or at home. A commonly used tool for patient self-reporting of quality of life is the EQ5D health status questionnaire which, while limited in scope, has general applicability across a range of health interventions. In this article we examine the issues relating to online patient self-reporting using this questionnaire and the wider implications for the online reporting of health status. PMID- 25133766 TI - Rounds reports: Early experiences of using printed summaries of electronic medical records in a large teaching medical hospital. AB - This article describes the rationale, processes, technology, and results of creating of a paper-based rounds report that is now used by our entire institution for efficient inpatient work rounds and checkout rounds that are routinely done in virtually every hospital, both academic and private, in the US. The results of a survey of clinicians suggests that printed rounds reports have markedly improved rounding efficiency, saved substantial amounts of physician time, standardized checkout processes, and improved patient safety. PMID- 25133767 TI - What you see is not what you get in the PDF document format. AB - The sharing and storage of scientific knowledge, information and data are today mainly in digitized form, which will become the predominant means of communicating scientific work in the future. One of the best-established formats is the open standard of PDF (Portable Document Format), which is renowned for its flexibility and stability. In this article, we expose a major flaw in the format with respect to the security of confidential information, such that even organizations responsible for safeguarding and setting the standards for data management were unintentionally revealing confidential patient data. By collecting and analysing a random sample of files from a health informatics organization, we demonstrate the extent of the problem and determine its cause by code analysis of an example. In conclusion, we suggest the development of a knowledge-sharing format that does not demand expert skills for safe usage: WYSIWYS (What You See Is What You Store). PMID- 25133768 TI - Robotic agents for supporting community-dwelling elderly people with memory complaints: Perceived needs and preferences. AB - Researchers in robotics have been increasingly focusing on robots as a means of supporting older people with cognitive impairment at home. The aim of this study is to explore the elderly's needs and preferences towards having an assistive robot in the home. In order to ensure the appropriateness of this technology, 30 subjects aged 60 and older with memory complaints were recruited from the Memory Clinic of the Broca Hospital. We conducted an interview-administered questionnaire that included questions about their needs and preferences concerning robot functions and modes of action. The subjects reported a desire to retain their capacity to manage their daily activities, to maintain good health and to stimulate their memory. Regarding robot functions, the cognitive stimulation programme earned the highest proportion of positive responses, followed by the safeguarding functions, fall detection and the automatic help call. PMID- 25133769 TI - Matching AIDS and tuberculosis registry data to identify AIDS/tuberculosis comorbidity cases in California. AB - The purpose of this study was to evaluate the sensitivity and positive predictive value (PPV) of a registry data linkage procedure used in the California AIDS and Tuberculosis (TB) Registry Data Linkage Study to identify AIDS/TB comorbidity cases in California. The California AIDS registry data from 1981 to 2006 were linked to the California TB registry data from 1996 to 2006 using LinkPlus, a probabilistic record linkage program developed by the Centers for Disease Control and Prevention, and matched results were manually reviewed to determine true or false matches. We estimated the sensitivity of this procedure to range from 98.0 per cent (95% confidence interval, CI: 97.3%, 98.7%) to 98.8 per cent (95% CI: 98.1%, 99.2%), and the PPV to be 100 per cent (95% CI: 96.8%, 100.0%). Our study demonstrated the feasibility of using this linkage procedure to match AIDS and TB registry data with a very high degree of accuracy. PMID- 25133770 TI - Electronic patient records in action: Transforming information into professionally relevant knowledge. AB - The implementation of generic models for organizing information in complex institutions like those in healthcare creates a gap between standardization and the need for locally relevant knowledge. The present study addresses how this gap can be bridged by focusing on the practical work of healthcare staff in transforming information in EPRs into knowledge that is useful for everyday work. Video recording of shift handovers on a rehabilitation ward serves as the empirical case. The results show how extensive selections and reorganizations of information in EPRs are carried out in order to transform information into professionally relevant accounts. We argue that knowledge about the institutional obligations and professional ways of construing information are fundamental for these transitions. The findings point to the need to consider the role of professional knowledge inherent in unpacking information in efforts to develop information systems intended to bridge between institutional and professional boundaries in healthcare. PMID- 25133771 TI - Personal health records: Consumer attitudes toward privacy and security of their personal health information. AB - Personal health record (PHR) systems are a subject of intense interest in the move to improve healthcare accessibility and quality. Although a number of vendors continue to put forward PHR systems, user-centered design research has lagged, and it has not been clear what features are important to prospective PHR users. Here, we report on a user-centered design study that combines qualitative and quantitative approaches to investigate several dimensions relevant to PHR design, and to look at the effect of health status on user needs. The results indicate that health status, especially disability and chronic illness, is relevant to PHR design. Further, the results provide empirical evidence about the role of privacy and security in users' attitudes toward PHR use. The exact nature of these attitudes differs from widely held perceptions about consumer values in healthcare information management. PMID- 25133772 TI - Maximizing acceptability and usefulness of an automated telephone intervention: Lessons from a developmental mixed-methods approach. AB - The objective was to describe the utility of mixed methods to inform the development of an automated telephone intervention to improve patients' compliance with asthma medication. As part of intervention development for a larger trial, we conducted 15 focus groups (n = 53) to design and develop calls, and to identify factors influencing intervention acceptability and usefulness. We piloted four call types and interviewed 64 participants to further improve call content and receptivity to the intervention. Feedback led to several changes to the intervention scripts and eventual calls, and an initial pilot led us to drop one of the calls. During the pilot, we reached 43 percent of target participants; 74 percent of those stayed on the call until it ended. This process provided key insights about automated calls, and may have broader applicability for the development of automated interventions designed to help patients manage a variety of chronic conditions. PMID- 25133774 TI - Genome-wide characterization of insertion and deletion variation in chicken using next generation sequencing. AB - Insertion and deletion (INDEL) is one of the main events contributing to genetic and phenotypic diversity, which receives less attention than SNP and large structural variation. To gain a better knowledge of INDEL variation in chicken genome, we applied next generation sequencing on 12 diverse chicken breeds at an average effective depth of 8.6. Over 1.3 million non-redundant short INDELs (1-49 bp) were obtained, the vast majority (92.48%) of which were novel. Follow-up validation assays confirmed that most (88.00%) of the randomly selected INDELs represent true variations. The majority (95.76%) of INDELs were less than 10 bp. Both the detected number and affected bases were larger for deletions than insertions. In total, INDELs covered 3.8 Mbp, corresponding to 0.36% of the chicken genome. The average genomic INDEL density was estimated as 0.49 per kb. INDELs were ubiquitous and distributed in a non-uniform fashion across chromosomes, with lower INDEL density in micro-chromosomes than in others, and some functional regions like exons and UTRs were prone to less INDELs than introns and intergenic regions. Nearly 620,253 INDELs fell in genic regions, 1,765 (0.28%) of which located in exons, spanning 1,358 (7.56%) unique Ensembl genes. Many of them are associated with economically important traits and some are the homologues of human disease-related genes. We demonstrate that sequencing multiple individuals at a medium depth offers a promising way for reliable identification of INDELs. The coding INDELs are valuable candidates for further elucidation of the association between genotypes and phenotypes. The chicken INDELs revealed by our study can be useful for future studies, including development of INDEL markers, construction of high density linkage map, INDEL arrays design, and hopefully, molecular breeding programs in chicken. PMID- 25133775 TI - Sirt1 and Sirt6 mediate beneficial effects of rosiglitazone on hepatic lipid accumulation. AB - BACKGROUND: Sirtuin (Sirt), a sensor of the cell metabolic state, regulates glucose and lipid metabolism. The aim of this study was to address whether rosiglitazone (RGZ) alters hepatic Sirt1 and whether Sirt1 and/or Sirt6 have a regulatory role in the protective effects of RGZ on hepatocyte steatosis. METHODS: To investigate the effect of RGZ on hepatic Sirt1, rats were administered with RGZ for 6 weeks. The involvement of Sirt1/6 in the RGZ-mediated effect against hepatic steatosis was evaluated by single or double knockdown of Sirt1 and Sirt6 in a hepatocyte steatosis model. RESULTS: RGZ in vivo increased Sirt1 expression and its activity in rat livers. In a hepatocyte steatosis model, RGZ significantly reduced lipid accumulation and activated the Sirt1/6-LKB1-AMPK pathway. Sirt1 knockdown abolished the effects of RGZ with regard to hepatocyte fat accumulation and the Sirt1/6-LKB1-AMPK pathway, suggesting that Sirt1 is a key regulator of RGZ-mediated metabolic processes. Sirt6 knockdown inhibited the protective effects of RGZ to a lesser extent than Sirt1, and double knockdown of Sirt1/6 showed no synergistic effects. CONCLUSION: Our results demonstrate that Sirt1/6 are involved in the RGZ-mediated effects on hepatocyte steatosis, and the regulatory effects of Sirt1 and Sirt6 are not synergistic but compensatory for improving hepatocyte steatosis. PMID- 25133776 TI - Silver-catalyzed domino hydroarylation/cycloisomerization reactions of ortho alkynylbenzaldehydes: an entry to functionalized isochromene derivatives. AB - A Ag-catalyzed versatile and efficient access to 1H,1-arylisochromenes is reported. Starting from ortho-alkynylbenzaldehydes bearing various substitution patterns on the benzaldehyde and alkynyl units, the use of silver triflate (10 mol %) allowed a domino hydroarylation/cycloisomerization reaction process, leading to aryl-functionalized 1H-isochromene (>10 compounds, 80-98% yields). Notably, the reaction conditions were also compatible with benzaldehydes bearing an aliphatic-substituted alkynyl moiety with modest to good yields (34-88%, 10 compounds). PMID- 25133778 TI - Adaptive evolution and divergence of SERPINB3: a young duplicate in great Apes. AB - A series of duplication events led to an expansion of clade B Serine Protease Inhibitors (SERPIN), currently displaying a large repertoire of functions in vertebrates. Accordingly, the recent duplicates SERPINB3 and B4 located in human 18q21.3 SERPIN cluster control the activity of different cysteine and serine proteases, respectively. Here, we aim to assess SERPINB3 and B4 coevolution with their target proteases in order to understand the evolutionary forces shaping the accelerated divergence of these duplicates. Phylogenetic analysis of primate sequences placed the duplication event in a Hominoidae ancestor (~30 Mya) and the emergence of SERPINB3 in Homininae (~9 Mya). We detected evidence of strong positive selection throughout SERPINB4/B3 primate tree and target proteases, cathepsin L2 (CTSL2) and G (CTSG) and chymase (CMA1). Specifically, in the Homininae clade a perfect match was observed between the adaptive evolution of SERPINB3 and cathepsin S (CTSS) and most of sites under positive selection were located at the inhibitor/protease interface. Altogether our results seem to favour a coevolution hypothesis for SERPINB3, CTSS and CTSL2 and for SERPINB4 and CTSG and CMA1. A scenario of an accelerated evolution driven by host-pathogen interactions is also possible since SERPINB3/B4 are potent inhibitors of exogenous proteases, released by infectious agents. Finally, similar patterns of expression and the sharing of many regulatory motifs suggest neofunctionalization as the best fitted model of the functional divergence of SERPINB3 and B4 duplicates. PMID- 25133777 TI - HPLC-MS/MS analyses show that the near-Starchless aps1 and pgm leaves accumulate wild type levels of ADPglucose: further evidence for the occurrence of important ADPglucose biosynthetic pathway(s) alternative to the pPGI-pPGM-AGP pathway. AB - In leaves, it is widely assumed that starch is the end-product of a metabolic pathway exclusively taking place in the chloroplast that (a) involves plastidic phosphoglucomutase (pPGM), ADPglucose (ADPG) pyrophosphorylase (AGP) and starch synthase (SS), and (b) is linked to the Calvin-Benson cycle by means of the plastidic phosphoglucose isomerase (pPGI). This view also implies that AGP is the sole enzyme producing the starch precursor molecule, ADPG. However, mounting evidence has been compiled pointing to the occurrence of important sources, other than the pPGI-pPGM-AGP pathway, of ADPG. To further explore this possibility, in this work two independent laboratories have carried out HPLC-MS/MS analyses of ADPG content in leaves of the near-starchless pgm and aps1 mutants impaired in pPGM and AGP, respectively, and in leaves of double aps1/pgm mutants grown under two different culture conditions. We also measured the ADPG content in wild type (WT) and aps1 leaves expressing in the plastid two different ADPG cleaving enzymes, and in aps1 leaves expressing in the plastid GlgC, a bacterial AGP. Furthermore, we measured the ADPG content in ss3/ss4/aps1 mutants impaired in starch granule initiation and chloroplastic ADPG synthesis. We found that, irrespective of their starch contents, pgm and aps1 leaves, WT and aps1 leaves expressing in the plastid ADPG cleaving enzymes, and aps1 leaves expressing in the plastid GlgC accumulate WT ADPG content. In clear contrast, ss3/ss4/aps1 leaves accumulated ca. 300 fold-more ADPG than WT leaves. The overall data showed that, in Arabidopsis leaves, (a) there are important ADPG biosynthetic pathways, other than the pPGI-pPGM-AGP pathway, (b) pPGM and AGP are not major determinants of intracellular ADPG content, and (c) the contribution of the chloroplastic ADPG pool to the total ADPG pool is low. PMID- 25133779 TI - Changes in gastric and lung microflora with acid suppression: acid suppression and bacterial growth. AB - IMPORTANCE: The use of acid suppression has been associated with an increased risk of upper and lower respiratory tract infections in the outpatient setting but the mechanism behind this increased risk is unknown. We hypothesize that this infection risk results from gastric bacterial overgrowth with subsequent seeding of the lungs. OBJECTIVES: To determine if acid-suppression use results in gastric bacterial overgrowth, if there are changes in lung microflora associated with the use of acid suppression, and if changes in lung microflora are related to full column nonacid gastroesophageal reflux. DESIGN, SETTING, AND PARTICIPANTS: A 5 year prospective cohort study at a tertiary care center where children ages 1 to 18 years were undergoing bronchoscopy and endoscopy for the evaluation of chronic cough. Acid-suppression use was assessed through questionnaires with confirmation using an electronic medical record review. MAIN OUTCOMES AND MEASURES: Our primary outcome was to compare differences in concentration and prevalence of gastric and lung bacteria between patients who were and were not receiving acid suppression therapy. We compared medians using the Wilcoxon signed rank test and determined prevalence ratios using asymptotic standard errors and 95% confidence intervals. We determined correlations between continuous variables using Pearson correlation coefficients and compared categorical variables using the Fisher exact test. RESULTS: Forty-six percent of patients taking acid-suppression medication had gastric bacterial growth compared with 18% of untreated patients (P = .003). Staphylococcus (prevalence ratio, 12.75 [95% CI, 1.72-94.36]), Streptococcus (prevalence ratio, 6.91 [95% CI, 1.64-29.02]), Veillonella (prevalence ratio, 9.56 [95% CI, 1.26-72.67]), Dermabacter (prevalence ratio, 4.78 [95% CI, 1.09-21.02]), and Rothia (prevalence ratio, 6.38 [95% CI, 1.50 27.02]) were found more commonly in the gastric fluid of treated patients. The median bacterial concentration was higher in treated patients than in untreated patients (P = .001). There was no difference in the prevalence (P > .23) of different bacterial genera or the median concentration of total bacteria (P = .85) in the lungs between treated and untreated patients. There were significant positive correlations between proximal nonacid reflux burden and lung concentrations of Bacillus (r = 0.47, P = .005), Dermabacter (r = 0.37, P = .008), Lactobacillus (r = 0.45, P = .001), Peptostreptococcus (r = 0.37, P = .008), and Capnocytophagia (r = 0.37, P = .008). CONCLUSIONS AND RELEVANCE: Acid suppression use results in gastric bacterial overgrowth of genera including Staphylococcus and Streptococcus. Full-column nonacid reflux is associated with greater concentrations of bacteria in the lung. Additional studies are needed to determine if acid suppression-related microflora changes predict clinical infection risk; these results suggest that acid suppression use may need to be limited in patients at risk for infections. PMID- 25133781 TI - Programmable resistive-switch nanowire transistor logic circuits. AB - Programmable logic arrays (PLA) constitute a promising architecture for developing increasingly complex and functional circuits through nanocomputers from nanoscale building blocks. Here we report a novel one-dimensional PLA element that incorporates resistive switch gate structures on a semiconductor nanowire and show that multiple elements can be integrated to realize functional PLAs. In our PLA element, the gate coupling to the nanowire transistor can be modulated by the memory state of the resistive switch to yield programmable active (transistor) or inactive (resistor) states within a well-defined logic window. Multiple PLA nanowire elements were integrated and programmed to yield a working 2-to-4 demultiplexer with long-term retention. The well-defined, controllable logic window and long-term retention of our new one-dimensional PLA element provide a promising route for building increasingly complex circuits with nanoscale building blocks. PMID- 25133780 TI - Rearing in seawater mesocosms improves the spawning performance of growth hormone transgenic and wild-type coho salmon. AB - Growth hormone (GH) transgenes can significantly accelerate growth rates in fish and cause associated alterations to their physiology and behaviour. Concern exists regarding potential environmental risks of GH transgenic fish, should they enter natural ecosystems. In particular, whether they can reproduce and generate viable offspring under natural conditions is poorly understood. In previous studies, GH transgenic salmon grown under contained culture conditions had lower spawning behaviour and reproductive success relative to wild-type fish reared in nature. However, wild-type salmon cultured in equal conditions also had limited reproductive success. As such, whether decreased reproductive success of GH transgenic salmon is due to the action of the transgene or to secondary effects of culture (or a combination) has not been fully ascertained. Hence, salmon were reared in large (350,000 L), semi-natural, seawater tanks (termed mesocosms) designed to minimize effects of standard laboratory culture conditions, and the reproductive success of wild-type and GH transgenic coho salmon from mesocosms were compared with that of wild-type fish from nature. Mesocosm rearing partially restored spawning behaviour and success of wild-type fish relative to culture rearing, but remained lower overall than those reared in nature. GH transgenic salmon reared in the mesocosm had similar spawning behaviour and success as wild type fish reared in the mesocosm when in full competition and without competition, but had lower success in male-only competition experiments. There was evidence of genotype*environmental interactions on spawning success, so that spawning success of transgenic fish, should they escape to natural systems in early life, cannot be predicted with low uncertainty. Under the present conditions, we found no evidence to support enhanced mating capabilities of GH transgenic coho salmon compared to wild-type salmon. However, it is clear that GH transgenic salmon are capable of successful spawning, and can reproduce with wild type fish from natural systems. PMID- 25133782 TI - Stimuli-sensitive breathing of Cucurbit[7]uril cavity: monitoring through the environment responsive fluorescence of 1'-hydroxy-2'-acetonaphthone (HAN). AB - In this work, we have focused on the supramolecular interactions of a water soluble host Cucurbit[7]uril (CB[7]) with an excited state intramolecular proton transfer (ESIPT) probe 1'-hydroxy-2'-acetonaphthone (HAN) through steady-state and time-resolved fluorescence measurements. In water HAN is almost nonfluorescent in nature with a very low fluorescence quantum yield (Phi = 0.009). With gradual addition of CB[7] absorption maximum of HAN is red-shifted (292 cm(-1)) and hence confirming the formation of an inclusion complex in the ground state between HAN and CB[7]. Due to this complexation CB[7] offers a hydrophobic microenvironment to the HAN which is completely different from that of homogeneous water. Upon encapsulation into the nanocavity of CB[7], HAN exhibits a 20-fold increase in fluorescence intensity along with a 36 nm (1618 cm(-1)) hypsochromic shift in emission maxima. This hypsochromic shift is an indication about the modulation of excited state photophysical behavior of HAN due to the formation of HAN-CB[7] inclusion complex. Moreover, huge partition coefficient of HAN from water to CB[7] along with a~ 12-fold increase in fluorescence lifetime confirm the favorable interaction between HAN and CB[7]. We have also observed the stimuli-sensitive (temperature and cationic stimuli) breathing of CB[7] cavity i.e., in the presence of different additives the portals of CB[7] open up to release HAN in water and take up the additives. Time resolved anisotropy measurements further indicate about the probable location of HAN inside the CB[7]. The observation of a 1.7 ns component in the presence of CB[7] signifies the highly restricted rotational motion of HAN inside the cavity of CB[7] corroborates our finding. PMID- 25133783 TI - Clinical exome sequencing: the new standard in genetic diagnosis. PMID- 25133784 TI - Diffusion and seed shape: intertwined parameters in the synthesis of branched metal nanostructures. AB - Branched nanocrystals display interesting optical and catalytic properties on account of their high surface areas and tips with small radii of curvatures. However, many synthetic routes toward branched nanocrystals result in inhomogeneous samples on account of asymmetric branching. Seed-mediated coreduction is a recently developed route to symmetrically branched nanocrystals where the symmetry of the seeds is transferred to the final stellated morphologies. Here, general guidelines to stellated nanocrystals are outlined by surveying coreduction of Au and Pd precursors in the presence of a variety of shape-controlled Au seeds to achieve Au/Pd nanostructures. Single-crystalline, twinned, and anisotropic seeds were analyzed to expand the classes of stellated nanostructures synthetically accessible. Significantly, single-crystalline Au seeds adopt {100}-terminated intermediates prior to branching, regardless of initial seed shape. We compared these results with those obtained with shape controlled Pd seeds, and seed composition was identified as an important synthetic parameter, with Pd seeds being more resistant to shape changes during overgrowth. This difference is attributed to the greater diffusion rate of Au atoms on Au seeds compared to Au atoms on Pd seeds. These results provide guidelines for the seeded synthesis of symmetrically branched nanocrystals and architecturally defined bimetallic nanostructures in general. PMID- 25133785 TI - Characteristics and survival to discharge of patients with STEMI between a PPCI capable hospital and a non-PPCI hospital: a prospective observational study. AB - INTRODUCTION: Primary percutaneous coronary intervention (PPCI) is a key therapeutic method in the treatment of ST-elevation myocardial infarction (STEMI). We studied the characteristics and survival to discharge in STEMI patients who presented in a PPCI-capable hospital and a non-PPCI hospital. PATIENTS AND METHODS: This prospective observational study included 240 consecutive patients. One basic questionnaire was distributed along with an explanatory letter to the participants, who were followed until discharge from the hospital or death. RESULTS: Of the 240 patients, 234 (97.5%) survived to hospital discharge. Only 6 (5%) patients who were initially presented to a non PPCI hospital died after inter-facility transfer. Also, 36 (92.3%) of the 39 patients with an intervening time of over 90 min were admitted initially in a non PPCI hospital. Although there was a statistically significant correlation between the type of the hospital and the delay from the onset of symptoms to PPCI (P=0.001), such correlation was not found between the delay PPCI and the outcome of the patients (P>0.05). CONCLUSION: Patients with STEMI may be transferred to a non-PPCI hospital due to the lack of prehospital triage. However, prompt inter facility transfer results in good outcome. PMID- 25133786 TI - Potential determinants of drink driving in young adults. AB - OBJECTIVE: The main purposes of this study were to examine the usefulness of the variables of the theory of planned behavior (viz. attitudes, social norms, and self-efficacy) and to explore the relationship between optimism bias and drink driving in young adults. In addition, we explored gender differences in drink driving with provision for the effect of variables such as driving frequency and alcohol consumption. METHODS: Data were collected via a questionnaire administered to 274 drivers (59.9% females) aged 18-30 years (24.36 +/- 2.96). RESULTS: The results obtained with provision for driving frequency revealed substantial differences in driving behaviors between genders. Thus, males were more prone to drink driving, perceived less disapproval by their significant others (parents and peers), and felt less able to avoid drinking-and-driving situations. In addition, they self-reported more frequent alcohol consumption and driving under the influence. The results also confirm the significance of peers' subjective norms and attitudes to drink driving in males. Overconfidence in their own driving skills for driving drunk and perceived behavioral control were found to be significant predictors for drink driving in females. Optimism bias also played a slightly significant role in predicting drink driving but only in females. CONCLUSIONS: The important practical implications of these results with a view to designing effective interventions to prevent the risks associated with drink driving in the young population are discussed. Interventions should focus on young people's perceptions of group norms and promoting cautionary driving choices and alternatives to drink driving. PMID- 25133789 TI - Influence of metal of the applicator on the dose distribution during brachytherapy. AB - This study explores how the metal materials of the applicator influence the dose distribution when performing brachytherapy for cervical cancer. A pinpoint ionization chamber, Monte Carlo code MCNPX, and treatment planning system are used to evaluate the dose distribution for a single Ir-192 source positioned in the tandem and ovoid. For dose distribution in water with the presence of the tandem, differences among measurement, MCNPX calculation and treatment planning system results are <5%. For dose distribution in water with the presence of the ovoid, the MCNPX result agrees with the measurement. But the doses calculated from treatment planning system are overestimated by up to a factor of 4. This is due to the shielding effect of the metal materials in the applicator not being considered in the treatment planning system. This result suggests that the treatment planning system should take into account corrections for the metal materials of the applicator in order to improve the accuracy of the radiation dose delivered. PMID- 25133787 TI - Development of a nuclear transformation system for Oleaginous Green Alga Lobosphaera (Parietochloris) incisa and genetic complementation of a mutant strain, deficient in arachidonic acid biosynthesis. AB - Microalgae are considered a promising source for various high value products, such as carotenoids, omega-3 and omega-6 polyunsaturated fatty acids (PUFA). The unicellular green alga Lobosphaera (Parietochloris) incisa is an outstanding candidate for the efficient phototrophic production of arachidonic acid (AA), an essential omega-6 PUFA for infant brain development and a widely used ingredient in the baby formula industry. Although phototrophic production of such algal products has not yet been established, estimated costs are considered to be 2-5 times higher than competing heterotrophic production costs. This alga accumulates unprecedented amounts of AA within triacylglycerols and the molecular pathway of AA biosynthesis in L. incisa has been previously elucidated. Thus, progress in transformation and metabolic engineering of this high value alga could be exploited for increasing the efficient production of AA at competitive prices. We describe here the first successful transformation of L. incisa using the ble gene as a selection marker, under the control of the endogenous RBCS promoter. Furthermore, we have succeeded in the functional complementation of the L. incisa mutant strain P127, containing a mutated, inactive version of the delta-5 (Delta5) fatty acid desaturase gene. A copy of the functional Delta5 desaturase gene, linked to the ble selection marker, was transformed into the P127 mutant. The resulting transformants selected for zeocine resistant, had AA biosynthesis partially restored, indicating the functional complementation of the mutant strain with the wild-type gene. The results of this study present a platform for the successful genetic engineering of L. incisa and its long-chain PUFA metabolism. PMID- 25133790 TI - Exposure to anticholinergic and sedative drugs, risk of falls, and mortality: an elderly inpatient, multicenter cohort. AB - This study aimed to assess whether exposure to anticholinergic and sedative medications and its evolution was associated with increased risk of in-hospital falls and all-cause mortality. Furthermore, results were compared with 2 definitions of drug burden index (DBI) against the outcomes.This observational, multicentric, and longitudinal study was conducted among patients aged 65 years or older, in 3 geriatric hospitals, in Francheville, Lyon, and Villeurbanne, France (duration of follow-up, 11.6 months). The exposure to anticholinergic and sedative medications was quantified using a DBI, at admission and at the end of observation for 337 patients. The evolution of exposure was the absolute difference between the index at admission and at the end of observation. The outcomes were in-hospital falls and all-cause mortality.Overall, 5.9% of patients experienced a fall. The risk of fall was nearly 3-fold in patients whose DBI increased during hospital stay compared to those with stable or decreased DBI (hazard ratio, 2.9 [1.14-7.12]; P = 0.03), after adjustment for comorbidities.The overall proportion of mortality was 6.5%. The evolution of DBI during hospital stay was not related to the risk of mortality (hazard ratio, 1.9 [0.8-4.4]; P = 0.14). Results were similar with the 2 definitions of DBI.Increased exposure to anticholinergic and sedative medications during hospital stay is associated with a higher risk of in-hospital falls but not with mortality. The DBI could be implemented in hospital, to guide prescription and reduce anticholinergic and sedative drug exposure. PMID- 25133791 TI - Lactulose-associated lithium toxicity: a case series. AB - BACKGROUND: Lactulose is commonly used for constipation and hepatic encephalopathy. Its adverse effects of dehydration and serum electrolyte imbalances are widely known. OBJECTIVE: This study aimed to describe a case series of 3 patients receiving lactulose who developed lithium toxicity. METHODS: The authors described a case series of 3 patients admitted to a large county psychiatric hospital who developed lithium toxicity while taking lactulose for constipation or hyperammonemia. RESULTS: In all 3 cases of lithium toxicity, the patients were prescribed with lithium for acute mania and lactulose for constipation or hyperammonemia. One case required the patient to be transferred to a local emergency department for further treatment. CONCLUSIONS: This case series shows the interaction between lithium and lactulose. It is postulated that lactulose's effects of volume depletion can lead to poor renal excretion of lithium. PMID- 25133792 TI - Influence of acoustic stimulation on the circadian and ultradian rhythm of premature infants. AB - The aim of the present study was to evaluate the development of the circadian rhythm of the salivary cortisol in premature infants and its correlation with the onset of the sleep-activity behavior pattern during the first 3 weeks of life under controlled light:dark conditions. Furthermore, we investigated the influence of acoustic stimulation by audiotaped lullabies or the maternal voice on the cortisol values and long-term sleep-activity patterns. The study was a block-randomized, prospective clinical trial with a study population of 62 preterm neonates (30<37 gestational age). We compared two study groups who listened either to music or to the maternal voice (music: N=20; maternal voice: N=20) with a matched control group (N=22). The acoustic stimulation took place every evening between 20:00 and 21:00 h for 30 min over a period of 2 weeks. The cortisol values and activity-rest behavior of the neonates were determined during the first 3 weeks of life on the 1st, 7th and 14th day. Actigraphic monitoring was used to record the activity pattern continuously over 24 h and a validated algorithm for neonates was used to estimate sleep and wakefulness. The saliva samples were obtained 10 min before and 10 min after the acoustic interventions for the study groups. Additionally, saliva samples were obtained from the control group seven times over a 24-h period (20:00, 21:00, 01:00, 05:00, 08:00, 13:00 and 17:00 h). The cortisol data were analyzed by fast Fourier transformation to assess periodic characteristics and frequencies. Hierarchical linear modeling was further performed for the statistical analysis. RESULTS: The cortisol rhythm analysis indicated a circadian rhythm pattern for only one premature infant, all others of the neonates showed no circadian or ultradian rhythm in cortisol. Cortisol level of the premature neonates was significantly higher during the first day of the study period at night-time (median: 17.1 nmol/L, IQR=9.7-24.4 nmol/L) than on days 7 (median: 9.6 nmol/L, IQR=4.7-14.6 nmol/L; Tukey-HSD, z=4.12, p<0.001) and 14 (IQR=5.8-13.7 nmol/L; Tukey-HSD, z=2.89, p<0.05). No significant effect of acoustic stimulation was observed on the cortisol concentration and sleep-wake behavior. The activity-sleep rhythm of preterm neonates was dominated by ultradian rhythm patterns with a prominent period length of 4 h (30.5%). Activity frequencies of neonates were also significantly higher overnight on the first study day (mean: 329+/-185.1 U) than of night seven (mean: 260.2+/-132.4 U; Tukey-HSD, z=2.50, p<0.05). Quiet-activity patterns increased, whereas high-activity patterns decreased during the observation period. Average sleep time increased significantly during the study time from day 1 to day 7 (Tukey-HSD, z=2.51, p<0.05). In conclusion, premature infants showed higher cortisol levels - without a circadian rhythmicity - and higher activity frequencies in the first days after birth which may reflect an adaptation process of neonates after birth. Cortisol concentrations and the activity patterns were not influenced by music interventions. PMID- 25133794 TI - Effects of fenofibric acid on diabetic macular edema: the MacuFen study. AB - PURPOSE: Fenofibrate reduced progression of diabetic retinopathy in two large randomized studies. The effect of 135 mg fenofibric acid on diabetic macular edema (DME) was evaluated in subjects with existing DME. METHODS: In this double blind, randomized, placebo-controlled study, 110 subjects with DME not requiring immediate photocoagulation or intraocular treatment with adequate diabetes and blood pressure control received either fenofibric acid or placebo once daily for 1 year. Total macula volume (TMV) and thickness were measured in the worse eye and all eligible eyes with time-domain optical coherence tomography at baseline and quarterly thereafter. RESULTS: TMV decreased by -0.35 mm(3) (within-group difference) after fenofibric acid treatment and by -0.11 mm(3) after placebo. The between-group comparison of the change was -0.25 mm(3) (95% confidence interval, CI, -0.645-0.155; p = 0.227, worse eye analysis). Weighted inner zone thickness and volume decreased by -18.7 um and -0.13 mm(3), respectively, for within group difference after fenofibric acid and by -3.1 um and -0.02 mm(3), respectively, after placebo. Considering all eligible eyes, thicknesses at central zone, mean inner zone, and entire retina decreased by -21.3 um, -19.8 um, and -20.4 um, respectively, after fenofibric acid. No between-group difference in changes of these measurements was observed. Triglycerides decreased by 23% after fenofibric acid (vs 4% after placebo, p = 0.001) and high-density lipoprotein cholesterol increased by 8% (vs 0.3%, p = 0.014). No safety concern was identified. CONCLUSION: Subjects treated with fenofibric acid had a modest improvement in TMV, although the study was probably underpowered to detect a benefit over placebo after 1 year. PMID- 25133796 TI - Application of rapid computer modeling in the analysis of the stabilization method in intraoperative femoral bone shaft fracture during revision hip arthroplasty - a case report. AB - BACKGROUND: Fractures of the femoral bone shaft during and after hip arthroplasty are a serious clinical problem. CASE REPORT: The paper presents the use of rapid computer modeling FEM 2D to optimize the stabilization of femoral shaft fracture in case of hip revision arthroplasty. CONCLUSIONS: Using the FEM modeling may be helpful for planning and assessment of orthopaedic treatment in similar cases. PMID- 25133797 TI - Isolated fracture of the hip stem prosthesis made of austenitic steel - a literature review. AB - Proper design and functioning of the hip joint ensure smooth motion over the full range in multiple planes. Any change in this arrangement may lead to joint damage, causing deformation, pain and loss of functionality. Hip replacement is a procedure intended to replace the damaged articular surfaces and replacing them with artificial components. However, as any surgical intervention, it carries the risk of serious complications. One of them are isolated stem fractures, consisting of breaking the implant inside the intramedullary canal without damaging the surrounding tissue. This article contains a review of the literature data concerning the clinical cases of isolated fractures of hip endoprosthesis stems made of austenitic stainless steel. Although stem fractures are one of the rarest complications of implantation, the lack of clear description of the causes of this phenomenon in the literature makes it worthwhile to take up on the subject. PMID- 25133793 TI - Regenerative medicine for the heart: perspectives on stem-cell therapy. AB - SIGNIFICANCE: Despite decades of progress in cardiovascular biology and medicine, heart disease remains the leading cause of death, and there is no cure for the failing heart. Since heart failure is mostly caused by loss or dysfunction of cardiomyocytes (CMs), replacing dead or damaged CMs with new CMs might be an ideal way to reverse the disease. However, the adult heart is composed mainly of terminally differentiated CMs that have no significant self-regeneration capacity. RECENT ADVANCES: Stem cells have tremendous regenerative potential and, thus, current cardiac regenerative research has focused on developing stem cell sources to repair damaged myocardium. CRITICAL ISSUES: In this review, we examine the potential sources of cells that could be used for heart therapies, including embryonic stem cells and induced pluripotent stem cells, as well as alternative methods for activating the endogenous regenerative mechanisms of the heart via transdifferentiation and cell reprogramming. We also discuss the current state of knowledge of cell purification, delivery, and retention. FUTURE DIRECTIONS: Efforts are underway to improve the current stem cell strategies and methodologies, which will accelerate the development of innovative stem-cell therapies for heart regeneration. PMID- 25133798 TI - A long-term macroecological analysis of the recovery of a waterbird metacommunity after site protection. AB - We used the so called "land-bridge island" or "nested-subsets" theory to test the resilience of a highly fragmented and perturbated waterbird metacommunity, after legal protection of 18 wetlands in the western Mediterranean. Sites were monitored during 28 years and two seasons per year. The metacommunity was composed by 44 species during breeding and 67 species during wintering, including shorebirds, ducks, herons, gulls and divers (Podicipedidae). We identified a strong nested pattern. Consistent with the fact that the study system was to a large extent a spatial biogeographical continuous for thousands of years, fragmented only during the last centuries due to human activities. Non-random selective extinction was the most likely historical process creating the nested pattern, operated by the differential carrying capacity (surface-area) of the remaining sites. We also found a positive temporal trend in nestedness and a decreasing trend in species turnover among sites (beta-diversity), indicating that sites are increasingly more alike to each other (i.e. increased biotic homogenization). This decreasing trend in beta-diversity was explained by an increasing trend in local (alpha) diversity by range expansion of half the study species. Regional (gamma) diversity also increased over time, indicating that colonization from outside the study system also occurred. Overall our results suggest that the study metacommunity is recovering from historical anthropogenic perturbations, showing a high long-term resilience, as expected for highly vagile waterbirds. However, not all waterbird groups contributed equally to the recovery, with most breeding shorebird species and most wintering duck species showing no geographical expansion. PMID- 25133799 TI - Improving facility performance in infectious disease care in Uganda: a mixed design study with pre/post and cluster randomized trial components. AB - BACKGROUND: The effects of two interventions, Integrated Management of Infectious Disease (IMID) training program and On-Site Support (OSS), were tested on 23 facility performance indicators for emergency triage assessment and treatment (ETAT), malaria, pneumonia, tuberculosis, and HIV. METHODS: The trial was implemented in 36 primary care facilities in Uganda. From April 2010, two mid level practitioners per facility participated in IMID training. Eighteen of 36 facilities were randomly assigned to Arm A, and received OSS in 2010 (nine monthly two-day sessions); 18 facilities assigned to Arm B did not receive OSS in 2010. Data were collected from Nov 2009 to Dec 2010 using a revised Ministry of Health outpatient medical form and nine registers. We analyzed the effect of IMID training alone by measuring changes before and during IMID training in Arm B, the combined effect of IMID training and OSS by measuring changes in Arm A, and the incremental effect of OSS by comparing changes across Arms A and B. RESULTS: IMID training was associated with statistically significant improvement in three indicators: outpatients triaged (adjusted relative risks (aRR) = 1.29, 99%CI = 1.01,1.64), emergency and priority patients admitted, detained, or referred (aRR = 1.59, 99%CI = 1.04,2.44), and pneumonia suspects assessed (aRR = 2.31, 99%CI = 1.50,3.55). IMID training and OSS combined was associated with improvements in six indicators: three ETAT indicators (outpatients triaged (aRR = 2.03, 99%CI = 1.13,3.64), emergency and priority patients admitted, detained or referred (aRR = 3.03, 99%CI = 1.40,6.56), and emergency patients receiving at least one appropriate treatment (aRR = 1.77, 99%CI = 1.10,2.84)); two malaria indicators (malaria cases receiving appropriate antimalarial (aRR = 1.50, 99%CI = 1.04,2.17), and patients with negative malaria test results prescribed antimalarial (aRR = 0.67, 99%CI = 0.46,0.97)); and enrollment in HIV care (aRR = 1.58, 99%CI = 1.32,1.89). OSS was associated with incremental improvement in emergency patients receiving at least one appropriate treatment (adjusted ratio of RR = 1.84,99%CI = 1.09,3.12). CONCLUSION: The trial showed that the OSS intervention significantly improved performance in one of 23 facility indicators. PMID- 25133800 TI - Evaluation of exome sequencing to estimate tumor burden in plasma. AB - Accurate estimation of systemic tumor load from the blood of cancer patients has enormous potential. One avenue is to measure the presence of cell-free circulating tumor DNA in plasma. Various approaches have been investigated, predominantly covering hotspot mutations or customized, patient-specific assays. Therefore, we investigated the utility of using exome sequencing to monitor circulating tumor DNA levels through the detection of single nucleotide variants in plasma. Two technologies, claiming to offer efficient library preparation from nanogram levels of DNA, were evaluated. This allowed us to estimate the proportion of starting molecules measurable by sequence capture (<5%). As cell free DNA is highly fragmented, we designed and provide software for efficient identification of PCR duplicates in single-end libraries with a varying size distribution. On average, this improved sequence coverage by 38% in comparison to standard tools. By exploiting the redundant information in PCR-duplicates the background noise was reduced to ~1/35,000. By applying our optimized analysis pipeline to a simulation analysis, we determined the current sensitivity limit to ~1/2400, starting with 30 ng of cell-free DNA. Subsequently, circulating tumor DNA levels were assessed in seven breast- and one prostate cancer patient. One patient carried detectable levels of circulating tumor DNA, as verified by break point specific PCR. These results demonstrate exome sequencing on cell-free DNA to be a powerful tool for disease monitoring of metastatic cancers. To enable a broad implementation in the diagnostic settings, the efficiency limitations of sequence capture and the inherent noise levels of the Illumina sequencing technology must be further improved. PMID- 25133801 TI - Mechanisms of analgesic and anti-inflammatory properties of Annona muricata Linn. (Annonaceae) fruit extract in rodents. AB - Unripe fruit of Annona muricata Linn. (Annonaceae) (soursop) is used in traditional African medicine for the treatment of neuralgia, rheumatism, and arthritic pain. This study sought to investigate the analgesic and anti inflammatory effects of lyophilized fruit extract of Annona muricata (AM) in rodents. The analgesic activity was evaluated using the mouse writhing, formalin, and hot-plate tests while the anti-inflammatory action was investigated using the carrageenan-induced rat paw edema and xylene-induced ear edema tests. Pretreatment with AM (50, 100, and 200 mg/kg, p.o.) produced dose-dependent (P<.001) inhibition of writhes and formalin-induced pain in the late phase. AM and morphine produced time-course increase in pain threshold in hot-plate test. However, the analgesic effect elicited by AM was reversed (P<.05) by naloxone pretreatment. Similarly, the time-dependent increase in paw circumference induced by carrageenan was inhibited by AM treatment with peak effect (0.23+/-0.10 cm; P<.001, 200 mg/kg; 6 h), which was comparatively similar to that of diclofenac treated. Further, the xylene-induced ear edema was significantly reduced by AM (50 or 100 mg/kg) pretreatment; however, the anti-inflammatory effect elicited by AM was prevented by pretreatment of mice with N(G)-nitro-l-arginine (20 mg/kg, i.p., nitric-oxide synthase inhibitor) 15 min before AM (200 mg/kg, p.o.). The in vitro cyclooxygenase assay also showed that AM produced concentration-dependent inhibition of both cyclooxygenase (COX)-1 and COX-2 activity by 39.44%+/-0.05% and 55.71%+/-0.12%, respectively, at 100 MUg/mL. In conclusion, A. muricata possesses analgesic effect through interaction with opioidergic pathway and anti inflammatory property through inhibition of chemical mediators of inflammation. PMID- 25133802 TI - Nanoparticle-based CT imaging technique for longitudinal and quantitative stem cell tracking within the brain: application in neuropsychiatric disorders. AB - A critical problem in the development and implementation of stem cell-based therapy is the lack of reliable, noninvasive means to image and trace the cells post-transplantation and evaluate their biodistribution, final fate, and functionality. In this study, we developed a gold nanoparticle-based CT imaging technique for longitudinal mesenchymal stem cell (MSC) tracking within the brain. We applied this technique for noninvasive monitoring of MSCs transplanted in a rat model for depression. Our research reveals that cell therapy is a potential approach for treating neuropsychiatric disorders. Our results, which demonstrate that cell migration could be detected as early as 24 h and up to one month post transplantation, revealed that MSCs specifically navigated and homed to distinct depression-related brain regions. We further developed a noninvasive quantitative CT ruler, which can be used to determine the number of cells residing in a specific brain region, without tissue destruction or animal scarification. This technique may have a transformative effect on cellular therapy, both for basic research and clinical applications. PMID- 25133803 TI - The integrated disease network. AB - The growing body of transcriptomic, proteomic, metabolomic and genomic data generated from disease states provides a great opportunity to improve our current understanding of the molecular mechanisms driving diseases and shared between diseases. The use of both clinical and molecular phenotypes will lead to better disease understanding and classification. In this study, we set out to gain novel insights into diseases and their relationships by utilising knowledge gained from system-level molecular data. We integrated different types of biological data including genome-wide association studies data, disease-chemical associations, biological pathways and Gene Ontology annotations into an Integrated Disease Network (IDN), a heterogeneous network where nodes are bio-entities and edges between nodes represent their associations. We also introduced a novel disease similarity measure to infer disease-disease associations from the IDN. Our predicted associations were systemically evaluated against the Medical Subject Heading classification and a statistical measure of disease co-occurrence in PubMed. The strong correlation between our predictions and co-occurrence associations indicated the ability of our approach to recover known disease associations. Furthermore, we presented a case study of Crohn's disease. We demonstrated that our approach not only identified well-established connections between Crohn's disease and other diseases, but also revealed new, interesting connections consistent with emerging literature. Our approach also enabled ready access to the knowledge supporting these new connections, making this a powerful approach for exploring connections between diseases. PMID- 25133805 TI - Helical versus all-trans conformations of oligo(ethylene glycol)-terminated alkanethiol self-assembled monolayers. AB - The complex mixture of conformational states exhibited by oligo(ethylene glycol) terminated alkanethiols on Ag and Au surfaces is explored by polarization dependent X-ray absorption spectroscopy. Three self-assembled monolayers (SAMs) with known helical or all-trans conformations are used as references to characterize a SAM with unknown conformations. This case study is used as a prototype for developing a systematic framework to extract the conformations of SAMs from the polarization dependence of several orbitals. In the case at hand, these are associated with the C-H/Rydberg bonds of the alkane, the C-H/Rydberg bonds of ethylene glycol, and the C-C bonds of the backbone. The C-H/Rydberg orbitals of the alkane and ethylene glycol are distinguished via the chemical shift of the corresponding C 1s core levels. PMID- 25133804 TI - Contrasting metabolism in perenniating structures of upland and lowland switchgrass plants late in the growing season. AB - BACKGROUND: Switchgrass (Panicum virgatum L.) is being developed as a bioenergy crop for many temperate regions of the world. One way to increase biomass yields is to move southern adapted lowland cultivars to more northern latitudes. However, many southerly adapted switchgrass germplasm can suffer significant winter kill in northerly climes. MATERIALS AND METHODS: Here, we have applied next-generation sequencing in combination with biochemical analyses to query the metabolism of crowns and rhizomes obtained from two contrasting switchgrass cultivars. Crowns and rhizomes from field-grown lowland (cv Kanlow) and upland (cv Summer) switchgrass cultivars were collected from three randomly selected post-flowering plants. Summer plants were senescing, whereas Kanlow plants were not at this harvest date. RESULTS: Principal component analysis (PCA) differentiated between both the Summer and Kanlow transcriptomes and metabolomes. Significant differences in transcript abundances were detected for 8,050 genes, including transcription factors such as WRKYs and those associated with phenylpropanoid biosynthesis. Gene-set enrichment analyses showed that a number of pathways were differentially up-regulated in the two populations. For both populations, protein levels and enzyme activities agreed well with transcript abundances for genes involved in the phenylpropanoid pathway that were up regulated in Kanlow crowns and rhizomes. The combination of these datasets suggests that dormancy-related mechanisms had been triggered in the crowns and rhizomes of the Summer plants, whereas the crowns and rhizomes of Kanlow plants had yet to enter dormancy. CONCLUSIONS: Delayed establishment of dormancy at more northerly latitudes could be one factor that reduces winter-survival in the high yielding Kanlow plants. Understanding the cellular signatures that accompany the transition to dormancy can be used in the future to select plants with improved winter hardiness. PMID- 25133806 TI - [Changes in the newest recommendations on Asthma Management and Prevention - GINA Report 2014. What should we pay attention to?]. PMID- 25133807 TI - Epidemiological situation of tuberculosis in Poland: part II. What are the causes of the different epidemiological situation in various regions of Poland? AB - INTRODUCTION: The different epidemiological situation of tuberculosis in various regions of Poland (higher and lower notification rates) was described previously by our group. The patients diagnosed with tuberculosis in the higher notification rate areas were younger and there were more cases of primary tuberculosis (tuberculous pleurisy and tuberculosis of chest lymph nodes) than in the patients diagnosed in the lower notification areas. The aim of the present study was to assess the possible causes of the different epidemiological situation of tuberculosis in various regions of Poland. MATERIAL AND METHODS: Analysis was done at the same regions as in the previous paper. A comparison was made between two groups: Group I, which included three voivodeships with higher rates of notification, from 23.7 to 32.3/100,000 (mean rates in the analysed period of time); and Group II, which included five voivodeships with lower notification rates (mean rates from 12.2 to 18.6/100,000). The wealth of the regions (GDP, gross domestic product per capita), the level of unemployment, and social status of the patients were analysed. We compared the population density in both regions. The results of treatment in both regions were also analysed. RESULTS: We did not find any differences in GDP and unemployment rates between the compared regions. The results of treatment were different in particular regions, but there was no clear tendency for worse results in voivodeships in Group I compared to voivodeships in Group II. However, the number of patients lost from observation was significantly higher in the regions from Group I than in those from Group II. There was also a significantly higher death rate from tuberculosis in younger patients (L 59 years) from Group I than from Group II. This is additional proof that the epidemiological situation in the two regions was different. Finally, we found that the mean density of population in the regions from Group I was higher than that from Group II. The density of population may influence transmission of tuberculosis. There is also the possibility that the differences in the epidemiological situation in various regions of Poland are caused by historical events. In the past the epidemiological situation of tuberculosis was much worse in the east of Europe than in the west. Just after the Second World War, according to the changes of the Polish territory, many Polish citizens (mainly ancestors of those from Group I) were displaced from the east to the west. CONCLUSIONS: In conclusion, the greater number of patients lost from observation, together with the higher density of population in the regions from Group I in comparison with those from Group II, seems to be partly responsible for the difference in the epidemiological situation in the two regions. It is also possible that some patients from Group I are more susceptible to infection and disease caused by Mycobacterium tuberculosis due to their ancestors, who lived in the east of Europe. PMID- 25133808 TI - Bronchoscopy in immediate diagnosis of smear negative tuberculosis. AB - BACKGROUND: Tuberculosis is a major public health problem. Almost 30% of cases of tuberculosis are known to be sputum smear negative. There is a diagnostic dilemma in such cases leading to inadvertent delays in management of these cases. The present study was planned to assess the role of bronchoscopy in immediate diagnosis of smear negative pulmonary tuberculosis. MATERIAL AND METHODS: The present study is a retrospective analysis of 132 sputum smear negative tuberculosis suspects who underwent bronchoscopic evaluation during the period 2002-2013. The diagnosis of tuberculosis was based on the finding of bacilli in aspirate or in tissue biopsy or the demonstration of caseous necrosis on tissue biopsy. RESULTS: The present study showed that bronchoscopy could lead to immediate, accurate diagnosis in 68.2% of suspected smear negative cases. Bronchial aspirate and bronchoalveolar lavage alone were diagnostic in 51.5% of such cases while tissue biopsy added to the yield in another 16.5% cases. CONCLUSIONS: The results of the present study suggests an important place of bronchoscopy in immediate diagnosis of suspected smear negative tuberculosis, thus avoiding inadvertent delays in diagnosing and instituting appropriate treatment. PMID- 25133809 TI - Stratification of patients with COPD according to the 2011 GOLD report. AB - INTRODUCTION: The authors aimed to compare the distribution of COPD based on the new GOLD grading with stadium based exclusively on spirometry. MATERIAL AND METHODS: Eligible patients had an average age of 64.8 years and smoked at least 10 pack-years. COPD was defined according to GOLD fixed cut-off criterion FEV1/FVC < 0.70. In all patients postbronchodilator spirometry was performed. Categories were defined with the mMRC dyspnoea scale and CAT scale. COPD exacerbations in the previous year and lung function were evaluated. Statistical comparisons were done using t-student test. RESULTS: 315 COPD patients, 99 (31.4%) women and 216 (68.6%) men, were examined. Mean pack-years in the whole group was 47.1 +/- 17.8. In women this figure was less than in men, 43.7 +/- 19.2 vs 49.5 +/- 16.5 (p > 0.05), respectively. At study entry, 144 subjects (45.7%) were current smokers, and the majority of them (n-87, 60.4%) belonged to category D - 26/66 (54.5%) women and 51/102 (50%) men. Based on spirometry alone, the patients were classified as moderate COPD 144 (45.71%), severe - 154 (48.89%), and very severe 17 (5.4%). According to the 2011 GOLD report stratification, 60 patients (19.04%) were graded as category A, 63 (20%) as category B, 24 (7.62%) as category C, and 168 (53.33%) as category D, although 21 (12.5% of them) were in category B, but the number of exacerbations classified them as category D. CONCLUSIONS: The COPD population is heterogeneous in reference to the symptoms, value of FEV1, and susceptibility to exacerbations. Clinical symptoms assessed using validated questionnaires characterized COPD patients better than the value of spirometric parameters (which are necessary for diagnosis of this disease). Some patients were difficult to classify, especially those belonging to category C. PMID- 25133810 TI - Prognostic value of serum C-reactive protein (CRP) and cytokeratin 19 fragments (Cyfra 21-1) but not carcinoembryonic antigen (CEA) in surgically treated patients with non-small cell lung cancer. AB - INTRODUCTION: The aim of the study was to assess the prognostic value of cytokeratin 19 fragments (Cyfra 21-1), carcinoembryonic antigen (CEA) and C reactive protein (CRP) in surgically treated NSCLC patients. MATERIAL AND METHODS: 50 NSCLC patients (25 adenocarcinoma, 21 squamous cell and 4 adenosquamous), clinical stages I and II, age 42-89 years, entered the study. CEA, Cyfra 21-1 and CRP concentrations were measured in serum taken before surgery, CEA and Cyfra 21-1 in 50 patients, CRP - in 46 patients. The survival was calculated from the date of surgical treatment until death or until the end of the observation time. The results were expressed as medians (95%CI). RESULTS: Cyfra 21-1 concentration was 2.1 (0.7-14.5) ng/mL. Survival time in the patients with Cyfra 21-1 <= 2 ng/mL, and > 2 ng/ /mL was 79 (14.85-88.2) and 29 (5.7-87.6) months, (p < 0.026). CEA concentration was 2.68 (0.87-72.7) ng/mL, significantly higher in adenocarcinoma than in squamous cell lung cancer - 4.38 ng/mL (1.67 41.35) vs. 2.2 ng/mL (1.0-6.1), p = 0.002. CRP concentration was 5.45 (0-122.6) mg/L. Significant dependence was found between CRP and pathological tumour size (pT). Median CRP values in pT1, pT2 and pT3+4 tumours were: 2.8 mg/L, 6.9 mg/L and 23.5 mg/L, respectively. Survival time of the patients with CRP <= 10 mg/L and CRP > 10 mg/L was 79 (14.85-88.2) and 29.5 (5.7-87.6) months, respectively (p = 0.045). CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only significant preoperative prognostic indicators (HR 2.08 and 2.04, respectively). Among the postoperative parameters, pathological stage of disease (p-stage) and pT were the significant prognostic indicators (HR 2.1 and 2.42, respectively). CONCLUSIONS: In the present study, concerning surgically treated NSCLC patients, preoperative CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only negative prognostic indicators, while pT and p-stage were significant postoperative prognostic indicators. PMID- 25133811 TI - Detecting Mycobacterium tuberculosis complex DNA, based on post-mortem examination of hilar lymph nodes with real-time PCR: initial study. AB - INTRODUCTION: According to the WHO, almost a third of the world population are thought to be infected with Mycobacterium tuberculosis. Some studies of the prevalence of latent tuberculosis infection (LTBI) have already been performed in Poland, showing that almost a quarter of the Mazovia population could be infected. It also indicated a higher prevalence of LTBI among seniors. Those studies were based on indirect diagnostic methods. MATERIAL AND METHODS: We randomly collected hilar lymph nodes from decedents aged 40 years and older during post-mortem examination. We excluded patients with previous confirmed tuberculosis. In addition, an autopsy was performed in all patients. Finally, we used real-time PCR Xpert MTB/RIF (Cepheid, USA) for the specific capture of mycobacterial DNA. RESULTS: Twenty-two of 23 patients had a negative result of the real-time PCR examination and no signs of caseous necrosis in hilar lymph nodes. We found the only positive sample in a patient with histopathological signs of tuberculosis (the presence of caseous necrosis in the specimens obtained from lymph nodes and lung). Due to the change of cartridges from version G3 to G4, further reactions were inhibited and no more post-mortem samples were tested. CONCLUSIONS: Real-time PCR Xpert MTB/RIF was capable of detecting M. tuberculosis complex DNA in a patient with tuberculosis recognised on autopsy. In the remaining patients, no M. tuberculosis complex DNA was found, in accordance with negative results of histological examination. Since the technology of cartridges has changed, it is no longer possible to use real-time PCR Xpert MTB/RIF (Cepheid USA) on post-mortem material. PMID- 25133812 TI - Methodological recommendations for the diagnostics of EGFR gene mutations and ALK gene rearrangement in the selection of non-small-cell lung cancer patients to molecularly targeted therapies. AB - Testing for EGFR gene mutations and ALK gene rearrangement is routinely used in advanced non-small-cell lung cancer for adequate patient selection to molecularly targeted therapies. We present Polish methodological recommendations for molecular analysis of EGFR and ALK genetic abnormalities. Recommendations specify clinical indications for testing, sample types and handling, as well as requirements for laboratories performing molecular diagnostics. PMID- 25133813 TI - Immediate hypersensitivity reaction with mango. AB - Hypersensitivity to the fruit mango is extremely rare and can exhibit either as immediate or delayed reactions. Since 1939, only 22 patients (10 with immediate type I reactions and 12 with delayed) have been documented with allergy to mango. History of atopy and geographical region may influence the type of reaction. Immediate reactions occurred most often in patients with history of atopy, while delayed reactions developed in non-atopic individuals. Clustering of delayed hypersensitivity reports from Australia and immediate reactions from Europe has been documented. We report a 50-year-old man with immediate type I hypersensitivity to mango, who developed cough, wheezing dyspnoea, generalised itching and abdominal discomfort after ingestion of mango. Life threatening event can also happen making it imperative to diagnose on time, so as to prevent significant morbidity and potential mortality. PMID- 25133815 TI - [Pneumocystis pneumonia in HIV-infected patients with cytomegalovirus co infection. Two case reports and a literature review]. AB - Pneumocystis pneumonia (PCP) is one of the infectious lung diseases diagnosed in HIV-infected patients. The pathogen responsible for the development of this opportunistic infection is an atypical fungus called Pneumocystis jiroveci. PCP remains the most common disorder diagnosed at the onset of acquired immunodeficiency syndrome (AIDS), especially in individuals not aware of their HIV infection. The most important risk factor of PCP development in HIV-infected person is the decrease of T CD4+ cell number below 200/mcL. Clinical symptoms consist of: chronic cough, dyspnoea and weakness. Arterial blood gas analysis often reveals the presence of hypoxaemia, and high-resolution computed tomography imaging shows diffuse ground glass opacities. Treatment is based on intravenous administration of trimetoprim-sulfamethoxasole. In patients with moderate and severe symptoms of PCP it is recommended that corticosteroids are used. Co infection with cytomegalovirus (CMV) is a poor prognostic sign in PCP. CMV related organ disease should be suspected in patients with T CD4+ cell number lower than 50/mcL. It is arguable whether CMV infection in symptomatic PCP patients should be treated. There are suggestions that corticosteroids used in PCP patients with CMV co-infection could promote the development of CMV pneumonia. In the present paper we present two patients with PCP, unaware of their HIV infection. In both cases a CMV co-infection was found. PMID- 25133814 TI - Granulomatosis with polyangiitis (Wegener's granulomatosis) with hard palate and bronchial perforations treated with rituximab - a case report. AB - We present a case of a 57-year-old woman suffering from granulomatosis with polyangiitis (GPA), who in the seventh months of immunosuppressive treatment (cyclophosphamide) progressed with new pulmonary changes and perforations of the hard palate and bronchi. Rituximab was introduced resulting in B-cell depletion and disappearance of anti-PR3 antibody. Palatal holes have substantially diminished and all bronchial perforations disappeared, covered by fibrous tissue. In the fourth month after rituximab administration, large scarring obstruction of the right main bronchus with upper and middle lobes atelectasis emerged. Because of increasing dyspnoea, stenotic bronchus was re-opened by bronchoscopy. Intervention was complicated by bilateral pneumothorax and later, on the seventh day, by fatal pulmonary bleeding. To our knowledge, this is the first report of GPA refractory to cyclophosphamide complicated by palatal and bronchial perforations. PMID- 25133816 TI - [Exercise-induced urticaria and angioedema - case report]. AB - Urticaria is a heterogeneous group of disorders, with various clinical manifestations and intensity of symptoms. Urticaria can be induced with a wide variety of environmental stimuli, such as cold, pressure, vibration, sunlight, exercise, temperature changes, heat, and water. In a select group of patients, exercise can induce a spectrum of urticaria symptoms, ranging from cutaneous pruritus and warmth, generalised urticaria, angioedema, and the appearance of such additional manifestations as collapse, upper respiratory distress, and anaphylaxis. Specific provocation tests should be carried out on an individual basis to investigate the suspected cause and proper diagnosis. Modification of activities and behaviour is the mainstay of treatment in patients with physical urticaria. The aim of this study was to emphasise that primary care paediatricians should be able to recognise physical urticaria, supply a patient with rescue medications, and refer him/her to a specialist. In the article, the authors present a 13-year-old girl with typical urticaria lesions and angioedema after exercise. According to the history, physical examination, and provocation test, exercise-induced urticaria and angioedema were diagnosed. PMID- 25133817 TI - [Ventilator-associated pneumonia and other infections]. AB - One of the fundamental elements of therapy in patients hospitalised in the Intensive Care Unit (ICU) is mechanical ventilation (MV). MV enables sufficient gas exchange in patients with severe respiratory insufficiency, thus preserving the proper functioning of organs and systems. However, clinical and experimental studies show that mechanical ventilation may cause severe complications, e.g. lung injury (VALI, VILI), systemic inflammatory response syndrome (SIRS), and, on rare occasions, multiple organ failure (MOF). Mechanical ventilation and especially endotracheal intubation are associated also with higher risk of infectious complications of the respiratory system: ventilator-associated respiratory infection (VARI) and ventilator-associated pneumonia (VAP). The complications of the MV listed above have a significant influence on the length of treatment and also on the increase of the costs of therapy and mortality of patients who stay in an ICU. These negative effects of supported breathing are the reasons for intensive research to find new biological markers of inflammation and lung injury, more sensitive and specific diagnostic instruments, more effective methods of therapy, and programs of prevention. The purpose of this article is the presentation of current knowledge concerning VAP-related infections, to allow pulmonologists and general practitioners to become more familiar with the problem. Basic and the most important data concerning the definition, epidemiology, pathophysiology, microbiology, diagnostics, treatment, and prevention of VAP have been included. Additionally, ventilator-associated tracheobronchitis (VAT) was discussed. PMID- 25133818 TI - Phylogeny in defining model plants for lignocellulosic ethanol production: a comparative study of Brachypodium distachyon, wheat, maize, and Miscanthus x giganteus leaf and stem biomass. AB - The production of ethanol from pretreated plant biomass during fermentation is a strategy to mitigate climate change by substituting fossil fuels. However, biomass conversion is mainly limited by the recalcitrant nature of the plant cell wall. To overcome recalcitrance, the optimization of the plant cell wall for subsequent processing is a promising approach. Based on their phylogenetic proximity to existing and emerging energy crops, model plants have been proposed to study bioenergy-related cell wall biochemistry. One example is Brachypodium distachyon, which has been considered as a general model plant for cell wall analysis in grasses. To test whether relative phylogenetic proximity would be sufficient to qualify as a model plant not only for cell wall composition but also for the complete process leading to bioethanol production, we compared the processing of leaf and stem biomass from the C3 grasses B. distachyon and Triticum aestivum (wheat) with the C4 grasses Zea mays (maize) and Miscanthus x giganteus, a perennial energy crop. Lambda scanning with a confocal laser scanning microscope allowed a rapid qualitative analysis of biomass saccharification. A maximum of 108-117 mg ethanol.g(-1) dry biomass was yielded from thermo-chemically and enzymatically pretreated stem biomass of the tested plant species. Principal component analysis revealed that a relatively strong correlation between similarities in lignocellulosic ethanol production and phylogenetic relation was only given for stem and leaf biomass of the two tested C4 grasses. Our results suggest that suitability of B. distachyon as a model plant for biomass conversion of energy crops has to be specifically tested based on applied processing parameters and biomass tissue type. PMID- 25133821 TI - Enantioselective C-H bond addition of pyridines to alkenes catalyzed by chiral half-sandwich rare-earth complexes. AB - Cationic half-sandwich scandium alkyl complexes bearing monocyclopentadienyl ligands embedded in chiral binaphthyl backbones act as excellent catalysts for the enantioselective C-H bond addition of pyridines to various 1-alkenes, leading to formation of a variety of enantioenriched alkylated pyridine derivatives in high yields and excellent enantioselectivity (up to 98:2 er). PMID- 25133819 TI - Effect of late planting and shading on cellulose synthesis during cotton fiber secondary wall development. AB - Cotton-rapeseed or cotton-wheat double cropping systems are popular in the Yangtze River Valley and Yellow River Valley of China. Due to the competition of temperature and light resources during the growing season of double cropping system, cotton is generally late-germinating and late-maturing and has to suffer from the coupling of declining temperature and low light especially in the late growth stage. In this study, late planting (LP) and shading were used to fit the coupling stress, and the coupling effect on fiber cellulose synthesis was investigated. Two cotton (Gossypium hirsutum L.) cultivars were grown in the field in 2010 and 2011 at three planting dates (25 April, 25 May and 10 June) each with three shading levels (normal light, declined 20% and 40% PAR). Mean daily minimum temperature was the primary environmental factor affected by LP. The coupling of LP and shading (decreased cellulose content by 7.8%-25.5%) produced more severe impacts on cellulose synthesis than either stress alone, and the effect of LP (decreased cellulose content by 6.7%-20.9%) was greater than shading (decreased cellulose content by 0.7%-5.6%). The coupling of LP and shading hindered the flux from sucrose to cellulose by affecting the activities of related cellulose synthesis enzymes. Fiber cellulose synthase genes expression were delayed under not only LP but shading, and the coupling of LP and shading markedly postponed and even restrained its expression. The decline of sucrose phosphate synthase activity and its peak delay may cause cellulose synthesis being more sensitive to the coupling stress during the later stage of fiber secondary wall development (38-45 days post-anthesis). The sensitive difference of cellulose synthesis between two cultivars in response to the coupling of LP and shading may be mainly determined by the sensitiveness of invertase, sucrose phosphate synthase and cellulose synthase. PMID- 25133820 TI - The Ca2+ sensor protein swiprosin-1/EFhd2 is present in neurites and involved in kinesin-mediated transport in neurons. AB - Swiprosin-1/EFhd2 (EFhd2) is a cytoskeletal Ca2+ sensor protein strongly expressed in the brain. It has been shown to interact with mutant tau, which can promote neurodegeneration, but nothing is known about the physiological function of EFhd2 in the nervous system. To elucidate this question, we analyzed EFhd2-/ /lacZ reporter mice and showed that lacZ was strongly expressed in the cortex, the dentate gyrus, the CA1 and CA2 regions of the hippocampus, the thalamus, and the olfactory bulb. Immunohistochemistry and western blotting confirmed this pattern and revealed expression of EFhd2 during neuronal maturation. In cortical neurons, EFhd2 was detected in neurites marked by MAP2 and co-localized with pre- and post-synaptic markers. Approximately one third of EFhd2 associated with a biochemically isolated synaptosome preparation. There, EFhd2 was mostly confined to the cytosolic and plasma membrane fractions. Both synaptic endocytosis and exocytosis in primary hippocampal EFhd2-/- neurons were unaltered but transport of synaptophysin-GFP containing vesicles was enhanced in EFhd2-/- primary hippocampal neurons, and notably, EFhd2 inhibited kinesin mediated microtubule gliding. Therefore, we found that EFhd2 is a neuronal protein that interferes with kinesin-mediated transport. PMID- 25133822 TI - Financial incentives for increasing uptake of HPV vaccinations: a randomized controlled trial. AB - OBJECTIVE: Uptake of human papillomavirus (HPV) vaccinations by 17- to 18-year old girls in England is below (<35%) target (80%). This trial assesses (a) the impact of financial incentives on uptake and completion of an HPV vaccination program, and (b) whether impacts are moderated by participants' deprivation level. It also assesses the impact of incentives on decision quality to get vaccinated, as measured by attitudes toward the vaccination and knowledge of its consequences. METHOD: One thousand 16- to 18-year-old girls were invited to participate in an HPV vaccination program: 500 previously uninvited, and 500 unresponsive to previous invitations. Girls randomly received either a standard invitation letter or a letter including the offer of vouchers worth L 45 (? 56; $73) for undergoing 3 vaccinations. Girls attending their first vaccination appointment completed a questionnaire assessing decision quality to be vaccinated. Outcomes were uptake of the first and third vaccinations and decision quality. RESULTS: The intervention increased uptake of the first (first-time invitees: 28.4% vs. 19.6%, odds ratio [OR] = 1.63, 95% confidence interval [CI; 1.08, 2.47]; previous nonattenders: 23.6% vs. 10.4%, OR = 2.65, 95% CI [1.61, 4.38]) and third (first-time invitees: 22.4% vs. 12%, OR = 2.15, 95% CI [1.32, 3.50]; previous nonattenders: 12.4% vs. 3%, OR = 4.28, 95% CI [1.92, 9.55]) vaccinations. Impacts were not moderated by deprivation level. Decision quality was unaffected by the intervention. CONCLUSIONS: Although the intervention increased completion of HPV vaccinations, uptake remained lower than the national target, which, in addition to cost effectiveness and acceptability issues, necessitates consideration of other ways of achieving it. PMID- 25133823 TI - Negative appearance evaluation is associated with skin cancer risk behaviors among American men and women. AB - OBJECTIVE: The current study aimed to examine links between appearance evaluation and skin cancer risk behaviors in men and women. METHOD: Data (N = 1,535; men, n = 873; women, n = 662) were extracted from Wave 4 of the National Longitudinal Study of Adolescent Health, a nationally representative, longitudinal dataset of U.S. adolescents and young adults. RESULTS: Skin cancer risk (i.e., number of hours spent outside for those with a history of severe sunburn and who were unlikely to use sunscreen) was significantly associated with participant gender, appearance evaluation, and their interaction. Both men and women who negatively evaluated their appearance were at significantly increased skin cancer risk, and this was particularly true for men. CONCLUSIONS: Negative appearance evaluation appears to be a correlate of engaging in behaviors that place individuals at risk of developing skin cancer. Future research may benefit from skin cancer prevention interventions that directly address appearance-based evaluations. PMID- 25133824 TI - Associations between socioeconomic status and obesity in diverse, young adolescents: variation across race/ethnicity and gender. AB - OBJECTIVE: This study examined the association between socioeconomic status (SES) and obesity risk during early adolescence, ages 10-13 years, and whether this association is present in different racial/ethnic and gender groups during 2 time points in early adolescence. METHOD: Data were from the Healthy Passages study, which enrolled 4,824 African American, Hispanic, and White 5th graders (ages 10 11) in a population-based, longitudinal study conducted in 3 U.S. metropolitan areas, and assessed them again 2 years later. Weight status was classified from measured body mass index using standard criteria into nonobese and obese (27% in 5th grade). SES was indexed based on highest education attainment in the household. RESULTS: Youth in the highest SES had a significantly lower prevalence of obesity than those of lower SES at both 5th and 7th grades when disregarding race/ethnicity. Within-racial/ethnic group analyses mostly confirmed this pattern for Hispanic and White youth, but not for African American youth. When also considering gender, the SES differential in obesity risk was more pronounced among White girls and 5th-grade Hispanic boys. CONCLUSION: Growing up in a high SES home, marked by having a member with at least a college degree, is associated with lower risk for obesity among Hispanic and White youth. For African American youth, there appears to be no association between SES and obesity. Thus the health advantage generally attributed to higher SES does not appear consistently across racial/ethnic groups for obesity in youth. Further research should identify influences on weight status beyond SES, especially among African American youth. PMID- 25133825 TI - Short-term affective recovery from hip fracture prospectively predicts depression and physical functioning. AB - OBJECTIVE: The goals of the current study were to determine the average affective experiences in the weeks and months after a hip fracture and assess how these experiences relate to physical and mental health functioning over time. METHOD: Positive and negative affect were assessed over time in a sample of older adults recruited after surgery for hip fracture (n = 500) and a comparison sample of older adults without hip fracture (n = 102) for 1 year longitudinally. RESULTS: For most of the individuals with a hip fracture, positive affect tended to increase over time and negative affect tended to decrease over time, suggesting that most people had at least some recovery of affect. In addition, individuals who showed a slower decrease in negative affect had higher levels of depression 1 year later, and individuals who showed a sharper increase in positive affect had superior physical function 1 year later. CONCLUSION: The current study provides evidence that both positive and negative affect in the first 12 weeks of recovery from hip fracture are potential targets for intervention to maximize psychological and physical recovery in the ensuing year. PMID- 25133826 TI - The association of metacognitive beliefs with emotional distress after diagnosis of cancer. AB - OBJECTIVE: Emotional distress after a diagnosis of cancer is normal and, for most people, will diminish over time. However, a significant minority of patients with cancer experience persistent or recurrent symptoms of emotional distress for which they need help. A model developed in mental health, the self-regulatory executive function model (S-REF), specifies that maladaptive metacognitive beliefs and processes, including persistent worry, are key to understanding why such emotional problems persist. This cross-sectional study explored, for the first, time whether metacognitive beliefs were associated with emotional distress in a cancer population, and whether this relationship was mediated by worry, as predicted by the S-REF model. METHOD: Two hundred twenty-nine participants within 3 months of diagnosis of, and before treatment for, primary breast or prostate cancer completed self-report questionnaires measuring anxiety, depression, posttraumatic stress disorder (PTSD) symptoms, metacognitive beliefs, worry, and illness perceptions. RESULTS: Regression analysis showed that metacognitive beliefs were associated with symptoms of anxiety, depression, and PTSD, and explained additional variance in these outcomes after controlling for age, gender, and illness perceptions. Structural equation modeling was consistent with cross-sectional hypotheses derived from the theory that metacognitive beliefs cause and maintain distress both directly and indirectly by driving worry. CONCLUSIONS: The findings provide promising first evidence that the S-REF model may be usefully applied in cancer. Further study is required to establish the predictive and clinical utility of these findings. PMID- 25133827 TI - Does the early feedback of results improve reassurance following diagnostic testing? A randomized controlled trial in patients undergoing cardiac investigation. AB - OBJECTIVE: Providing reassurance is often a critical component of the medical consultation. An important area that has not been addressed in the literature is how delay in providing the results of medical tests affects patient reassurance. In this study we investigated whether the early provision of a normal diagnostic result immediately following medical testing improves patient reassurance compared to results provided 4 weeks later. METHOD: We conducted a longitudinal randomized controlled trial and 1-month follow-up. Fifty-one cardiology outpatients with no known cardiac pathology referred for an echocardiogram test were randomized following normal test results to receive their test results from a cardiologist either immediately following testing or 4 weeks later. Measures of symptoms, anxiety, and health perceptions were taken prior to diagnostic testing. Reassurance was assessed immediately after the results were provided and 1 month later. RESULTS: Data analysis showed that the provision of early results had no impact on patient reassurance. Cardiac anxiety was strongly associated with lower reassurance; patients who were more anxious about their heart were significantly less reassured by a normal test result, both immediately following feedback and 1 month later. CONCLUSIONS: The early provision of test results had no impact on patient reassurance. The study suggests the identification and targeting of patients high in cardiac anxiety may be a better method for improving reassurance than reducing the waiting time for results following medical testing. PMID- 25133828 TI - Adolescent sexual health communication and condom use: a meta-analysis. AB - OBJECTIVE: Condom use is critical for the health of sexually active adolescents, and yet many adolescents fail to use condoms consistently. One interpersonal factor that may be key to condom use is sexual communication between sexual partners; however, the association between communication and condom use has varied considerably in prior studies of youth. The purpose of this meta-analysis was to synthesize the growing body of research linking adolescents' sexual communication to condom use, and to examine several moderators of this association. METHOD: A total of 41 independent effect sizes from 34 studies with 15,046 adolescent participants (M(age) = 16.8, age range = 12-23) were meta analyzed. RESULTS: Results revealed a weighted mean effect size of the sexual communication-condom use relationship of r = .24, which was statistically heterogeneous (Q = 618.86, p < .001, I2 = 93.54). Effect sizes did not differ significantly by gender, age, recruitment setting, country of study, or condom measurement timeframe; however, communication topic and communication format were statistically significant moderators (p < .001). Larger effect sizes were found for communication about condom use (r = .34) than communication about sexual history (r = .15) or general safer sex topics (r = .14). Effect sizes were also larger for communication behavior formats (r = .27) and self-efficacy formats (r = .28), than for fear/concern (r = .18), future intention (r = .15), or communication comfort (r = -.15) formats. CONCLUSIONS: Results highlight the urgency of emphasizing communication skills, particularly about condom use, in HIV/STI prevention work for youth. Implications for the future study of sexual communication are discussed. PMID- 25133831 TI - Narrative as a knowledge translation tool for facilitating impact: translating physical activity knowledge to disabled people and health professionals. AB - OBJECTIVE: Theoretically informed by narrative inquiry, this article examines the utility of stories as a possible tool for disseminating synthesized physical activity knowledge to adults with spinal cord injury (SCI) and health care professionals (HCPs) working with this population. It is the first research to systematically examine in this context the use of narratives as a knowledge translation tool. METHOD: Forty-three participants (15 adults with SCI; 13 peer mentors with SCI; and 15 HCPs) individually listened to an evidence-based story set in a rehabilitation hospital about the process of becoming physically active following SCI. Individual telephone interviews were conducted to examine participants' perceptions of the story. Qualitative data were analyzed using a thematic analysis. RESULTS: Five themes were inductively identified: (a) effective communication, (b) narrative authenticity, (c) credible messengers, (d) narrative format, and (e) narrative as a form of action. Together, the themes reveal that the story had utility, the various attributes that help explain why this is case, how the utility might be maximized, what the stories could do on and for people, and how the narratives can be used to support behavior change. CONCLUSIONS: The article advances knowledge by revealing the value of narrative as a means for disseminating evidence-based information to people with SCI and to HCPs. It also reveals that stories can be used to facilitate dialogue, teach, remind, reassure, and reinvigorate people. This article is a resource for enabling knowledge to be more effectively shared to different audiences and applying what we know in practice to help people live meaningful lives. PMID- 25133830 TI - Stressful life events, sexual orientation, and cardiometabolic risk among young adults in the United States. AB - OBJECTIVE: The goal of the present study was to examine whether sexual minority young adults are more vulnerable to developing cardiometabolic risk following exposure to stressful life events than heterosexual young adults. METHOD: Data came from the National Longitudinal Study for Adolescent Health (Shin, Edwards, & Heeren, 2009; Brummett et al., 2013), a prospective nationally representative study of U.S. adolescents followed into young adulthood. A total of 306 lesbian, gay, and bisexual (LGB) respondents and 6,667 heterosexual respondents met inclusion criteria for this analysis. Measures of cumulative stressful life events were drawn from all 4 waves of data collection; sexual orientation and cardiometabolic biomarkers were assessed at Wave 4 (2008-2009). RESULTS: Gay/bisexual men exposed to 1-2 (beta = 0.71, p = .01) and 5+ (beta = 0.87, p = .01) stressful life events had a statistically significant elevation in cardiometabolic risk, controlling for demographics, health behaviors, and socioeconomic status. Moreover, in models adjusted for all covariates, lesbian/bisexual (beta = 0.52, p = .046) women with 5+ stressful life events had a statistically significant elevation in cardiometabolic risk. There was no relationship between stressful life events and cardiometabolic risk among heterosexual men or women. CONCLUSION: Stressful life events during childhood, adolescence, and young adulthood place LGB young adults at heightened risk for elevated cardiometabolic risk as early as young adulthood. The mechanisms underlying this relationship require future study. PMID- 25133829 TI - Cognitive control in preadolescent children with risk factors for metabolic syndrome. AB - OBJECTIVE: To investigate the relationship between cognitive control and metabolic syndrome (MetS) risk factors in preadolescent children while controlling for aerobic fitness and weight status. METHODS: Hierarchical regression analyses were conducted using aerobic fitness, demographic, and MetS risk-factor variables in a sample of 2nd- and 3rd-grade children (n = 139) who performed a modified version of a flanker task to assess cognitive control. Flanker performance was also compared between children that met no MetS risk factor criteria (n = 70), and children who met 1 criterion or more (n = 69). RESULTS: Regression analyses indicated that after controlling for demographic variables and fitness, HDL cholesterol exhibited an independent negative association with flanker reaction time (RT). Group comparisons further revealed that children with no risk factors demonstrated overall shorter RT than the at risk group. In addition, at-risk children exhibited larger accuracy-interference scores (i.e., poorer performance) for the more difficult conditions of the flanker task that required the up-regulation of cognitive control to meet elevated task demands. CONCLUSIONS: These findings are consonant with the previous literature reporting a beneficial influence of aerobic fitness on cognitive control, and reveal new evidence that children without risk factors for MetS exhibit better inhibitory control and increased cognitive flexibility than do at-risk children. In addition to aerobic fitness, these risk factors may serve as important biomarkers for understanding the potential cognitive implications of MetS risk in younger generations. PMID- 25133832 TI - Are patient and relationship variables associated with participation of intimate partners in couples research? AB - BACKGROUND: Recruitment of participants for studies focusing on couples facing illness is a challenging task and participation decline may be associated with nonrandom factors creating bias. This study examines whether patient and relationship characteristics are associated with partner participation in research. METHOD: Patients invited to participate in a cross-sectional study on adaptation and quality of life after renal transplantation were asked to forward information about an add-on study to their partners. RESULTS: A total of 456 participating patients had a partner; 293 of the partners showed interest in the study and 206 actually completed the questionnaire. Backward logistic regression analyses revealed that demographic, illness, and personal characteristics of the patient were not associated with partner interest in the study nor actual partner participation. However, partners who indicated interest in the study showed more active engagement toward the patients (as reported by the patients). Furthermore, patients of partners who actually completed the questionnaire reported less negative affect and higher relationship satisfaction than patients whose partner did not participate in the study. DISCUSSION: It is encouraging that of the large number of variables tested, only 2 were associated with the participation of partners. Nevertheless, well-functioning couples appear to be overrepresented in our study, calling for specific effort to include marital distressed couples in research focusing on dyadic adaptation to illness. PMID- 25133833 TI - The myth of comfort food. AB - OBJECTIVE: People seek out their own idiosyncratic comfort foods when in negative moods, and they believe that these foods rapidly improve their mood. The purpose of these studies is to investigate whether comfort foods actually provide psychological benefits, and if so, whether they improve mood better than comparison foods or no food. METHODS: Participants first completed an online questionnaire to indicate their comfort foods and a variety of comparison foods. During two lab sessions a week apart from each other (and at least a week after the online questionnaire, counterbalanced in order), participants watched films that induced negative affect. In one session, participants were then served their comfort food. In the other, participants were served an equally liked noncomfort food (Study 1), a neutral food (Study 2), or no food (Studies 3 and 4). Short term mood changes were measured so that we could seek out psychological effects of these foods, rather than biochemical effects on mood from particular food components (e.g., sugars or vitamins). RESULTS: Comfort foods led to significant improvements in mood, but no more than other foods or no food. CONCLUSIONS: Although people believe that comfort foods provide them with mood benefits, comfort foods do not provide comfort beyond that of other foods (or no food). These results are likely not due to a floor effect because participants' moods did not return to baseline levels. Individuals may be giving comfort food "credit" for mood effects that would have occurred even in the absence of the comfort food. PMID- 25133834 TI - Implicit prototypes predict risky sun behavior. AB - OBJECTIVE: Despite the fact that skin cancer is highly avoidable, incidence and death rates in the United States continue to climb. The pattern is particularly problematic among young, White women, who sometimes overexpose themselves to harmful ultraviolet rays in hopes of being tan. Research has suggested that positivity toward prototypes of individuals who engage in unhealthy behavior, like tanning, influences the likelihood that an individual will personally engage in those behaviors. Although the prototype-to-behavior link is considered to operate automatically, researchers have typically relied on people's self reported evaluations of prototypes, which are more controlled and susceptible to self-presentational concerns. METHOD: In the present research, we developed a measure of implicit prototypes and compared it with measures of explicit prototypes in predicting the safe sun behavior of 731 women. RESULTS: Meta analysis of 5 different prototypes (i.e., cool, fun, healthy, intelligent, and attractive) suggested that implicit prototypes predicted more variance in women's current behavior, planned behavior, behavioral willingness, and tanning frequency than did explicit prototypes. CONCLUSION: Although some models recognize that health behavior may be based on automatic processes, they exclusively use measures of self-reported attitudes and prototypes to predict behavior. The results suggest that measuring implicit prototypes may provide important explanatory power. PMID- 25133835 TI - The question-behavior effect: genuine effect or spurious phenomenon? A systematic review of randomized controlled trials with meta-analyses. AB - OBJECTIVE: Simply answering questions about a specific behavior may change that behavior. This is known as the mere-measurement or question-behavior effect (QBE). Our objective was to synthesize the evidence for the QBE on health-related behaviors. METHOD: Included studies were randomized controlled trials that tested the effect of questionnaires or interviews about health-related behaviors and/or related cognitions compared with a no-measurement control condition or another form of measurement. Subgroup analyses were conducted to identify potential moderators. RESULTS: 41 studies were included assessing a range of health behaviors. Meta-analyses showed a small overall QBE effect (SMD = 0.09; 95% CI [0.04, 0.13]; k = 33). Studies showed moderate heterogeneity, variable risk of bias, and evidence of publication bias. No dose-response relationships were found from studies comparing more with less intensive measurement conditions. There were no significant differences in QBE by behavior, but QBEs for dental flossing, physical activity, and screening attendance were significantly different from 0. Findings were not altered by whether behavior or cognitions were measured, attitudes were or were not measured, studies used questionnaires or interviews, or outcomes were objective or self-reported. CONCLUSIONS: There is some evidence for the QBE on health-related behavior. However, risk of bias within studies and evidence of publication bias indicate that the observed small effect size may be overestimated, especially given that some studies included intervention techniques in addition to providing questionnaires. Preregistered high-quality trials with clear specification of intervention content are needed to confirm if and when measurement leads to behavior change. PMID- 25133836 TI - Anger, provider responses, and pain: prospective analysis of stem cell transplant patients. AB - OBJECTIVE: Patient anger can be challenging for providers, and may hinder the patient-provider relationship. Research on the relationships among patient anger, relationships with health care providers and medical outcomes, however, has been limited to anecdotal accounts and cross-sectional studies. This study examined relationships among patient anger, perceptions of provider positive support and negative interactions, by prospectively studying a sample of stem cell transplant (SCT) patients. METHOD: A prospective design was used to study patient anger, perceived positive support from providers and perceived negative interactions with providers among 88 SCT patients. Data were obtained upon patient's hospitalization before SCT and at 1, 2, and 3 month follow up periods. Repeated measures mixed models assessed relationships among study variables. RESULTS: Patient anger was associated with a gradual decline in perceived positive support and higher levels of concurrent perceived negative interactions with providers. Further, a significant lagged relationship was found such that patient anger was associated with increased perceived negative interactions with providers 1 month later. Exploratory analyses revealed that perceived negative interactions were also associated with higher levels of physical distress. Perceived positive support buffered the relationship between patient anger and physical distress, such that anger was not associated significantly with physical distress when perceived provider support was high. CONCLUSIONS: Patient anger may contribute to a deterioration of the patient-provider relationship, and contribute to negative medical outcomes including physical distress. The association between patient anger and physical distress may be reduced by supportive providers. PMID- 25133837 TI - Weight stigma mediates the association between BMI and self-reported health. AB - OBJECTIVE: Weight stigma is pervasive in the United States. We tested the hypothesis that stigma may be a mechanism through which obesity negatively affects self-reported health. Two studies examined whether perceived weight-based discrimination and concerns over weight stigma mediated the association between BMI and self-reported psychological health (Study 1) and physical health (Study 2). METHOD: In 2 online studies, adult community members completed measures of stigma-relevant mediators (perceived weight discrimination, weight stigma concerns) and provided their height and weight. In Study 1 (N = 171) participants also completed measures of psychological health (depression, self-esteem, quality of life), whereas participants in Study 2 (N = 194) also completed a measure of self-reported physical health. Process modeling was used to simultaneously test for mediation through perceived discrimination and stigma concerns independently as well as for serial mediation through both variables. RESULTS: Across both studies, we hypothesized and found support for serial mediation such that BMI was indirectly related to poorer self-reported health through its effect on perceived discrimination and concerns about stigma. Additionally, concerns about stigma mediated the association between BMI and health independent of perceived discrimination. CONCLUSIONS: Weight stigma is an important mediator of the association between BMI and self-reported health. Furthermore, results indicate that concerns about facing stigma in the future mediate the link between perceived past experiences of discrimination and psychological and physical health. PMID- 25133838 TI - Longitudinal association between child stress and lifestyle. AB - OBJECTIVE: Psychosocial stress has been linked with an unhealthy lifestyle but the relation's direction remains unclear. Does stress induce sleeping problems, comfort food consumption, and lower physical activity, or do these unhealthy lifestyle factors enhance stress? This study examined the bidirectional stress lifestyle relation in children. METHOD: The relation between stress and lifestyle was examined over 2 years in 312 Belgian children 5-12 years old as part of the Children's Body Composition and Stress study. Stress-related aspects were measured by questionnaires concerning negative events, negative emotions, and behavioral problems. The following lifestyle factors were assessed: physical activity (by accelerometers), sleep duration, food consumption (sweet food, fatty food, snacks, fruits and vegetables), and eating behavior (emotional, external, restrained). Bidirectional relations were examined with cross-lagged analyses. RESULTS: Certain stress aspects increased physical activity, sweet food consumption, emotional eating, restrained eating, and external eating (betas = .140-.319). All relations were moderated by sex and age: Dietary effects were mainly in the oldest children and girls; stress increased physical activity in the youngest, whereas it tended to decrease physical activity in the oldest. One reversed direction effect was found: Maladaptive eating behaviors increased anxiety feelings. CONCLUSIONS: Relations were mainly unidirectional: Stress influenced children's lifestyle. Stress stimulated eating in the absence of hunger, which could facilitate overweight. Consequently, families should realize that stress may influence children's diet, and problem-solving coping skills should be acquired. In contrast to recent findings, stress might also stimulate physical activity in the youngest as positive stress coping style. PMID- 25133839 TI - Psychosocial, health-promotion, and neurocognitive interventions for survivors of childhood cancer: a systematic review. AB - OBJECTIVE: Survivors of childhood cancer must contend with a number of medical and psychosocial vulnerabilities after their cancer treatment ends. Interventions have been developed to alleviate or prevent adverse outcomes among this population. This systematic review summarizes the efficacy of psychosocial, health behavior, and neurocognitive interventions for survivors of pediatric cancer. METHOD: Multiple databases were searched for studies published between January 1970 and June 2013. Studies were coded by 2 raters for methodological quality using the Effective Public Health Practice Project quality assessment tool. RESULTS: Twenty-four interventions were identified (7 psychosocial, 10 health behavior, and 7 neurocognitive). Eleven were controlled trials, of which 7 achieved medium to large effect sizes. Survivor interest, as demonstrated by consent rates, was high for interventions that did not require travel. CONCLUSIONS: Interventions using delivery methods varying from traditional counseling to computers achieved moderate to strong efficacy and merit replication. Survivor needs related to transition to adult-oriented health care and school reentry were not addressed by existing interventions. This review also revealed the absence of health behavior interventions for survivors in middle childhood and late adolescence. Intervention formats that are cost-effective and reduce participant burden should be prioritized for further testing. To broaden the reach and appeal of interventions, alternative delivery methods, such as mobile phone software applications, should be evaluated. PMID- 25133840 TI - Reflective and impulsive processes explain (in)effectiveness of messages promoting physical activity: a randomized controlled trial. AB - OBJECTIVE: The present study tested whether taking into account both the reflective and the impulsive processes of physical activity (PA) is helpful in understanding how, and for whom, PA-promoting messages will be (in)effective in changing behavior. METHOD: Participants (N = 101) were presented with a persuasive message promoting either PA (experimental condition) or healthy eating (control condition). Reflective intentions to be physically active were assessed both at baseline and after exposure to the message. Impulsive approach tendencies toward PA (IAPA) and sedentary behaviors (IASB) were assessed using a manikin task. The main outcome variable was accelerometer-assessed free time spent in moderate to vigorous physical activity (MVPA) over 1 week after exposure to the message. RESULTS: Although the PA-promoting message had no direct effect on MVPA, the results showed that (a) this message increased intentions to practice PA, notably among participants with low or moderate (but not high) baseline intentions; (b) objective MVPA was positively predicted by postmessage PA intentions and IAPA, and negatively predicted by IASB; and (c) postmessage PA intentions predicted MVPA for individuals with low or moderate (but not high) IASB. A follow-up moderated mediation analysis corroborated these earlier results, showing that PA-promoting messages positively predicted MVPA through postmessage intentions only among individuals with low or moderate baseline intentions and low or moderate IASB. CONCLUSIONS: By identifying 2 boundary conditions, this study revealed important insights in explaining when PA promoting messages will be effective to predict objective MVPA and when they will not. PMID- 25133841 TI - Five-factor personality traits and sleep: evidence from two population-based cohort studies. AB - OBJECTIVE: The current study examines associations between five factor personality traits and average sleep duration, sleep deficiency, and sleep problems. METHOD: The participants were from two population-based samples from Australia (n = 1,104, age range 31-41) and Finland (n = 1,623, age range 30-45). Self-reports of sleep behavior, sleep problems (Jenkin's scale), and five factor model personality traits (NEO-FFI) were collected. Associations between personality traits and sleep were analyzed with linear regressions. RESULTS: The results showed that higher extraversion, agreeableness, and conscientiousness were, in general, associated with better sleep, whereas higher neuroticism was associated with sleeping less well. Openness was not associated with sleep. Most of the associations were replicable between the samples from the two countries, but personality traits explained only small part of the variance in sleep behavior. CONCLUSIONS: Increasing the knowledge on personality and sleep may benefit more personalized treatment of sleep disorders and help in personnel selection to jobs in which it is critical to stay alert. However, longitudinal research is needed to confirm the current findings. PMID- 25133842 TI - How do general practitioners and patients make decisions about cardiovascular disease risk? AB - OBJECTIVE: Although current guidelines around the world recommend using absolute risk (AR) thresholds to decide whether cardiovascular disease (CVD) risk should be managed with lifestyle or medication, the use of AR in clinical practice is limited. The aim of this study was to explore the factors that influence general practitioner (GP) and patient decision making about CVD risk management, including the role of risk perception. METHODS: Qualitative descriptive study involving semi-structured interviews with 25 GPs and 38 patients in Australia in 2011-2012. Transcribed audio-recordings were thematically coded and a Framework Analysis method was used. RESULTS: GPs rarely mentioned AR thresholds but were influenced by their subjective perception of the patient's risk and motivation, and their own attitudes toward prevention, including concerns about medication side effects and the efficacy of lifestyle change. Patients were influenced by individual risk factors, their own motivation to change lifestyle, and attitudes toward medication: initially negative, but this improved if medication was more effective than lifestyle. High perceived risk led to medication being recommended by GPs and accepted by patients, but this was not necessarily based on AR. Patient perceptions of high risk also increased motivation to change lifestyle, particularly if they were resistant to the idea of taking medication. CONCLUSIONS: Perceived risk, motivation, and attitudes appeared to be more important than AR thresholds in this study. CVD risk management guidelines could be more useful if they include strategies to help GPs consider patients' risk perception, motivation, and attitudes as well as evidence-based recommendations. PMID- 25133843 TI - A social rank explanation of how money influences health. AB - OBJECTIVE: Financial resources are a potent determinant of health, yet it remains unclear why this is the case. We aimed to identify whether the frequently observed association between absolute levels of monetary resources and health may occur because money acts an indirect proxy for a person's social rank. METHOD: To address this question we examined over 230,000 observations on 40,400 adults drawn from two representative national panel studies; the British Household Panel Survey and the English Longitudinal Study of Ageing. We identified each person's absolute income/wealth and their objective ranked position of income/wealth within a social reference-group. Absolute and rank income/wealth variables were then used to predict a series of self-reported and objectively recorded health outcomes in cross-sectional and longitudinal analyses. RESULTS: As anticipated, those with higher levels of absolute income/wealth were found to have better health than others, after adjustment for age, gender, education, marital status, and labor force status. When evaluated simultaneously the ranked position of income/wealth but not absolute income/wealth predicted all health outcomes examined including: objective measures of allostatic load and obesity, the presence of long-standing illness, and ratings of health, physical functioning, role limitations, and pain. The health benefits of high rank were consistent in cross-sectional and longitudinal analyses and did not depend on the reference group used to rank participants. CONCLUSIONS: This is the first study to demonstrate that social position rather than material conditions may explain the impact of money on human health. PMID- 25133845 TI - The relationship between the belief in a genetic cause for breast cancer and bilateral mastectomy. AB - OBJECTIVE: Most women develop causal beliefs following diagnosis with breast cancer and these beliefs can guide decisions around their care and management. Bilateral mastectomy rates are increasing, although the benefits of this surgery are only established in a small percentage of women. In this study we investigated the relationship between causal beliefs and the decision to have a bilateral mastectomy. METHOD: Women (N = 2,269) from the Army of Women's breast cancer research registry completed an online survey. Women were asked what they believed caused their cancer and responses were coded into 8 causal categories. Participants were also asked about the type of surgery they underwent following their breast cancer diagnosis. The odds ratios for having a double mastectomy were calculated for each causal category using random/bad luck as a referent category. RESULTS: Hormonal factors (22%) and genetics (19%) were the most common causal belief, followed by don't know (19%), environmental toxins (11%), negative emotions (9%), poor health behavior (8%), other (6%) and random/bad luck (6%). Compared with the referent category, the odds ratio of having a bilateral mastectomy was significantly higher in both the genetics and hormonal causal belief groups (OR = 2.36, 95% CI [1.38, 4.02] and OR = 1.98, 95% CI [1.16, 3.38], respectively). CONCLUSIONS: Beliefs in a genetic cause for breast cancer are common and are associated with high rates of bilateral mastectomy. This is despite evidence that the actual genetic contribution to breast cancer is much lower than perceived and that bilateral mastectomy is, in most cases, unlikely to improve survival. (PsycINFO Database Record PMID- 25133844 TI - Variations in sleep characteristics and sleep-related impairment in at-risk college drinkers: a latent profile analysis. AB - OBJECTIVE: Sleep disturbance and heavy drinking increase risk of negative consequences in college students. Limited research exists on how they act synergistically, and the overall nature of sleep and sleep-related impairment in college student drinkers is poorly understood. A latent profile analysis was conducted on the sleep characteristics and daytime sleep-related consequences of college student drinkers who were at-risk based on Alcohol Use Disorders Identification Test-Consumption scores. METHODS: Participants (N = 312, mean age = 18.90 (0.97) years) consumed a mean (SD) of 20.93 (13.04) drinks per week. Scores on the 10 items of the Sleep/Wake Behavior Problems Scale (SWPS) were the class indicators. RESULTS: Four classes best described the sleep and sleep related consequences of at-risk college drinkers. Classes represented different gradients and types of sleep patterns and sleep-related impairment; nearly half the sample reported late bedtimes and daytime consequences of insufficient sleep. Subsequent validation analyses indicated that these classes were directly correspondent with severity of alcohol consumption, alcohol-related consequences illicit substance use, and perceived health. CONCLUSIONS: These findings indicate the presence of significant heterogeneity in college drinkers' sleep patterns and experiences of sleep-related impairment. Class differences significantly impact the level of alcohol and drug use and the consequences members experience. Greater alcohol use and sleep/wake problems are associated with increased risk for negative consequences for certain classes. These results suggest that college drinking interventions could benefit from the incorporation of sleep-related content and the value in adding brief alcohol assessments and interventions to other college health treatments. PMID- 25133846 TI - The impact of self-affirmation on health-behavior change: a meta-analysis. AB - OBJECTIVES: Self-affirmation (induced by reflecting upon important values, attributes, or social relations) appears to reduce defensive resistance to health risk information and increase subsequent readiness for health behavior change. However, these effects of self-affirmation have yet to be subjected to formal, quantitative integration. Consequently, the current article reports a meta analysis of the impact of self-affirmation on outcomes at 3 key points in the process of health-behavior change: (a) message acceptance, (b) intentions to change, and (c) subsequent behavior. METHOD: The literature search identified 144 experimental tests of the effects of manipulating self-affirmation on these outcomes. Effect sizes were extracted and meta-analyzed. RESULTS: Across 34 tests of message acceptance (N = 3,433), 64 tests of intentions (N = 5,564), and 46 tests of behavior (N = 2,715), random effects models indicated small but reliable positive effects of self-affirmation on each outcome: acceptance, d+ = .17(CI = .03 to .31); intentions, d+ = .14 (CI = .05 to .23); behavior, d+ = .32 (CI = .19 to .44). Findings held across a range of health problems and behaviors. CONCLUSIONS: The results suggest that deploying self-affirmation inductions alongside persuasive health information has positive effects, promoting message acceptance, intentions to change, and subsequent behavior. Though the effects are small in magnitude, they are comparable to those obtained in meta-analyses of other health-behavior change interventions. These findings are relevant to researchers and practitioners working to understand why people resist beneficial health information and how such resistance can be reduced. PMID- 25133847 TI - Tricksterdom in narratives of young adult cancer: performances of uncertainty, subversion, and possibility. AB - OBJECTIVE: As people with cancer attempt the difficult task of giving voice to life with illness, they often turn to mythic figures and stories (e.g., when people talk about battling cancer or embarking on a journey toward recovery). Little attention has been paid to the mythic figure of the trickster, recently identified by Arthur Frank (2009) as a prominent trope in some narrative accounts of illness. We investigated the prevalence of 3 tricksterly themes expressed within young adults' stories of cancer: destabilizing social or cosmic order (uncertainty), challenging dominant expectations for human life (subversion), and exploring alternative ways of viewing the world (possibility). METHOD: We recruited 21 young adults with cancer from across Canada and conducted semistructured interviews. We then analyzed their stories using some elements of thematic, structural, and dialogical/performative narrative analysis-drawing attention to what was told and how/to whom were they told (Crossley, 2000; Frank, 2012; Riessman, 2008). RESULTS: We describe each of the 3 themes in turn (i.e., uncertainty, subversion, and possibility) using excerpts from 6 interview transcripts, and show how they meaningfully converge into an interpretive framework of tricksterdom. CONCLUSION: We conclude that the 3 themes of uncertainty, subversion, and possibility seem to come together as tricksterly performances, disrupting audiences' expectations of more typical forms of cancer narratives and calling attention to less familiar, structured, and "tellable" ways of narrating illness. PMID- 25133848 TI - The roles of self-efficacy and motivation in the prediction of short- and long term adherence to exercise among patients with coronary heart disease. AB - OBJECTIVES: Poor adherence to regular exercise is a documented challenge among people with heart disease. Identifying key determinants of exercise adherence and distinguishing between the processes driving short- and long-term adherence to regular exercise is a valuable endeavor. The purpose of the present study was to test a model of exercise behavior change, which incorporates motivational orientations and self-efficacy for exercise behavior, in the prediction of short- and long-term exercise adherence. METHOD: Male and female patients (N = 801) hospitalized for coronary heart disease were recruited from 3 tertiary care cardiac centers and followed for a period of 1 year after hospital discharge. A prospective, longitudinal design was used to examine the roles of motivation and self-efficacy (measured at recruitment and at 2 and 6 months after discharge) in the prediction of exercise behavior at 6 and 12 months. Baseline measures of exercise and clinical and demographic covariates were included in the analyses. RESULTS: Structural equation modeling showed that both autonomous motivation and self-efficacy were important determinants of short-term (6-month) exercise behavior regulation, but that only autonomous motivation remained a significant predictor of long-term (12-month) exercise behavior. Self-efficacy partially mediated the relationship between motivation for exercise and 6-month exercise behavior. CONCLUSIONS: This research confirmed the roles of autonomous motivation and self-efficacy in the health behavior change process and emphasized the key function of autonomous motivation in exercise maintenance. Theoretical and cardiac rehabilitation program applications of this research are discussed. PMID- 25133849 TI - Synthesis of benzobicycloheptanones via the trap of photogenerated ketene methide intermediate with olefins. AB - Irradiation of ortho-formyl dienes with UV light led to benzobicycloheptanones in high yields and chemoselectivities via a photogenerated ketene methide/Diels Alder cascade reaction. The reaction mechanism was proposed to be a [1,5]-H shift process rather than a radical pathway based on control experiments. DFT calculations indicate that the energy of transition states is responsible for the high chemoselectivity observed in this protocol. PMID- 25133850 TI - Bioavailability and biological effect of engineered silver nanoparticles in a forest soil. AB - The extensive use of silver nanoparticles (SNPs) as antimicrobial in food, clothing and medicine, leads inevitably to a loss of such nanomaterial in soil and water. Little is known about the effects of soil contamination, in particular, on microbial cells, which play a fundamental ecological role. In this work, the impact of SNPs on forest soil has been studied, investigating eco physiological indicators of microbial biomass and microbial diversity with culture-dependent and independent techniques. Moreover, SNPs bioavailability and uptake were assessed. Soil samples were spiked with SNPs at two different concentrations (10 and 100 MUg g(-1)dw) and incubated with the relative controls for 30, 60 and 90 days. The overall parameters showed a significant influence of the SNPs on the soil microbial community, revealing a marked shift after 60 days of incubation. PMID- 25133851 TI - Influence of residual polymer on nanoparticle deposition in porous media. AB - Although surface coatings and free polymers are known to affect the mobility of nanoparticles in water-saturated porous media, the influence of these compounds on nanoparticle deposition behavior has received limited attention. A series of column experiments was conducted to evaluate the transport and retention of quantum dots (QDs) coated with a synthetic polymer, polyacrylic acid-octylamine (PAA-OA). Initial column studies, conducted with three size fractions of Ottawa sand, resulted in unusual solid-phase retention profiles, characterized by low QD deposition near the column inlet and increasing solid-phase concentrations along the column until a plateau or limiting capacity was reached near the column midpoint. Mathematical modeling studies indicated that the observed retention behavior could not be reproduced using one-dimensional simulators based on either clean-bed filtration theory or a modified filtration theory (MFT) model that incorporated a maximum retention capacity. Additional column studies demonstrated that changes in the inlet end plate configuration designed to ensure uniform flow did not alter the observed effluent breakthrough curves (BTCs) or shape of the retention profile. Subsequent QD transport experiments, pretreated by flushing with a pulse of PAA-OA solution, resulted in almost complete QD breakthrough with minimal retention. It is postulated that free polymer was preferentially adsorbed onto the solid surface near the column inlet, thereby preventing QD attachment, whereas in the down-gradient portion of the column, QDs attached to the solid phase without competition from the polymer. These findings reveal the importance of accounting for the influence of coconstituents on nanoparticle deposition and demonstrate the need to simulate both transport and retention data when assessing nanoparticle mobility in porous media. PMID- 25133852 TI - Malignancy risk stratification in thyroid nodules with nondiagnostic results at cytologic examination: combination of thyroid imaging reporting and data system and the Bethesda System. AB - PURPOSE: To evaluate the malignancy risks of thyroid nodules with nondiagnostic results at ultrasonography (US)-guided fine-needle aspiration biopsy ( FNAB fine needle aspiration biopsy ) and the criteria for selecting those for repeat US guided FNAB fine-needle aspiration biopsy according to the thyroid imaging reporting and data system ( TIRADS thyroid imaging reporting and data system ). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. Five hundred forty-eight nondiagnostic nodules were included. US features of internal composition, echogenicity, margin, calcifications, shape, and vascularity were evaluated, and thyroid nodules were classified according to TIRADS thyroid imaging reporting and data system . TIRADS thyroid imaging reporting and data system category 3 included nodules without any suspicious features of solidity, hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, and taller-than-wide shape. Categories 4a, 4b, 4c, and 5 included nodules with one, two, three or four, or five suspicious US features. The malignancy risk was calculated. RESULTS: Of the 548 nodules, 40 (7.3%) were malignant and 508 (92.7%) were benign. The malignancy risks of categories 3 and 4a nodules were 0.8% and 1.8%, respectively, whereas the malignancy risks of categories 4b, 4c, and 5 nodules were 6.1%, 14.4%, and 31%. In the 294 nodules larger than 10 mm, the malignancy risks of categories 3, 4a, 4b, 4c, and 5 nodules were 0.9%, 1.3%, 0%, 15%, and 33%, respectively. In the 254 nodules measuring 10 mm or smaller, the malignancy risks of categories 3, 4a 4b, 4c, and 5 nodules were 0%, 2.7%, 14%, 14.3%, and 31%. CONCLUSION: Nondiagnostic thyroid nodules without suspicious US features and those with one suspicious feature can be followed up with US, but nondiagnostic nodules with two or more suspicious features should undergo repeat US-guided FNAB fine-needle aspiration biopsy. PMID- 25133854 TI - Temperature-dependent wear mechanisms for magnetron-sputtered AlTiTaN hard coatings. AB - AlTiTaN coatings have been demonstrated to have high thermal stability at temperatures up to 900 degrees C. It has been speculated that the high oxidation resistance promotes an improved wear resistance, specifically for dry machining applications. This work reports on the influence of temperature up to 900 degrees C on the wear mechanisms of AlTiTaN hard coatings. DC magnetron-sputtered coatings were obtained from an Al(46)Ti(42)Ta(12) target, keeping the substrate bias at -100 V and the substrate temperature at 265 degrees C. The coatings exhibited a single-phase face-centered cubic AlTiTaN structure. The dry sliding tests revealed predominant abrasion and tribo-oxidation as wear mechanisms, depending on the wear debris formed. At room temperature, abrasion leading to surface polishing was observed. At 700 and 800 degrees C, slow tribo-oxidation and an amorphous oxide formed reduced the wear rate of the coating compared to room temperature. Further, an increase in temperature to 900 degrees C increased the wear rate significantly due to fast tribo-oxidation accompanied by grooving. The friction coefficient was found to decrease with temperature increasing from 700 to 900 degrees C due to the formation of oxide scales, which reduce adhesion of asperity contacts. A relationship between the oxidation and wear mechanisms was established using X-ray diffraction, Raman spectroscopy, scanning electron microscopy, surface profilometry, confocal microscopy, and dynamic secondary ion mass spectrometry. PMID- 25133855 TI - Therapist adherence in individual cognitive-behavioral therapy for binge-eating disorder: assessment, course, and predictors. AB - While cognitive-behavioral therapy (CBT) is the most well-established treatment for binge-eating disorder (BED), little is known about process factors influencing its outcome. The present study sought to explore the assessment of therapist adherence, its course over treatment, and its associations with patient and therapist characteristics, and the therapeutic alliance. In a prospective multicenter randomized-controlled trial comparing CBT to internet-based guided self-help (INTERBED-study), therapist adherence using the newly developed Adherence Control Form (ACF) was determined by trained raters in randomly selected 418 audio-taped CBT sessions of 89 patients (25% of all sessions). Observer-rated therapeutic alliance, interview-based and self-reported patient and therapist characteristics were assessed. Three-level multilevel modeling was applied. The ACF showed adequate psychometric properties. Therapist adherence was excellent. While significant between-therapist variability in therapist adherence was found, within-therapist variability was non-significant. Patient and therapist characteristics did not predict the therapist adherence. The therapist adherence positively predicted the therapeutic alliance. The ACF demonstrated its utility to assess therapist adherence in CBT for BED. The excellent levels of therapist adherence point to the internal validity of the CBT within the INTERBED study serving as a prerequisite for empirical comparisons between treatments. Variability between therapists should be addressed in therapist trainings and dissemination trials. PMID- 25133856 TI - Short-term effectiveness of an online behavioral training in migraine self management: a randomized controlled trial. AB - Behavioral training (BT) is recommended as a supplementary preventive treatment for migraine. Online interventions have been successful in promoting health behavior change, the evidence for online BT in migraine is limited, however. This randomized controlled trial aimed to determine the post-treatment effectiveness of online BT (n = 195) compared to a waitlist control group (WLC; n = 173) on migraine attack frequency (primary outcome), headache self-efficacy and locus of control (secondary outcomes). BT aims to counteract attacks in the prodromal stage through early detection of prodromal features and self-management via physical relaxation and cognitive behavioral regulation, and was offered with minimal e-mail support in eight online lessons. Results showed that 120 (62%) participants completed BT. A decrease of 20-25% in migraine attack frequency was found in both conditions without a between-group difference (ES = 0.02, p = .71). BT participants improved more than WLC participants on migraine related self efficacy (ES = 0.86, p < .001), developed more internal (ES = 0.57, p < .001), and less external control (ES = 0.78, p < .001). To conclude, results at post training did not corroborate that improvements in migraine attack frequency were due to online BT, the waitlist control group improved accordingly. However, positive effects of BT on self-efficacy and locus of control were established. We have to await the long term effects to see if improvements in psychological variables translate to a reduction in migraine headache. PMID- 25133858 TI - Synthesis and optophysical properties of dimeric aza-BODIPY dyes with a push-pull benzodipyrrolidone core. AB - A series of benzodipyrrolidone-based dimeric aza-BODIPY dyes with a push-pull structure are synthesized. Single crystal X-ray diffraction demonstrates these extended aza-BODIPY dyes are planar. The resulting aza-BODIPY chromophores exhibit intense absorption in the 450-800 nm regions and possess lower-lying LUMO energy levels. Furthermore, the push-pull substituents on aza-BODIPYs core have a positive effect on their optophysical properties. PMID- 25133857 TI - Visual disability rates in a ten-year cohort of patients with anterior visual pathway meningiomas. AB - PURPOSE: To examine the visual outcome of anterior visual pathway meningioma (AVPM) patients followed for at least one year. METHODS: Data were collected on demographics, clinical course and management. Visual disability was classified at the first and last examination as follows: I--no visual disability; II--mild visual defect in one eye; III--mild visual defect in both eyes; IV--loss of driver's license; V--legally blind. RESULTS: Eight-one AVPM patients had their tumor originate in the clinoid process in 23 (28%), sphenoid-wing area in 18 (22%), cavernous sinus in 15 (19%), tuberculum sellae in 8 (10%), and mixed in 17 (21%). On last examination, 46 patients (57%) had good visual acuity in one or both eyes (Class I or II) and 17 (21%) were mildly affected in both eyes. The rate of Class IV disability was 16%, and Class V disability was 6%. CONCLUSIONS: Attention needs to be addressed to the considerable proportion of patients with AVPM (22% in this study) who may lose their driver's license or become legally blind. Occupational therapists should play an important role in the multidisciplinary management of those patients to help them adapt to their new physical and social situation. IMPLICATIONS FOR REHABILITATION: Anterior visual pathway meningiomas (AVPMs) are commonly not life-threatening but they can lead to profound visual disability, especially when the tumor originates in the tuberculum sellae and cavernous sinus. Particular attention should be paid to visual acuity and visual field deficits, as these can profoundly affect the patient's quality of life including ability to drive and activities of daily living. The interdisciplinary management of patients with AVPM should include the neurosurgeon, neuro-ophthalmologist and occupational therapist. Also, early intervention by the occupational therapist can help patients adapt to their current physical and social situation and return to everyday tasks more rapidly. PMID- 25133859 TI - Highly efficient functional GexPb1-xTe based thermoelectric alloys. AB - Methods for enhancement of the direct thermal to electrical energy conversion efficiency, upon development of advanced thermoelectric materials, are constantly investigated mainly for efficient implementation of thermoelectric devices in automotive vehicles, for converting the waste heat generated in such engines into useful electrical power and thereby reduction of the fuel consumption and CO2 emission levels. It was recently shown that GeTe based compounds and specifically GeTe-PbTe rich alloys are efficient p-type thermoelectric compositions. In the current research, Bi2Te3 doping and PbTe alloying effects in GexPb1-xTe alloys, subjected to phase separation reactions, were investigated for identifying the phase separation potential for enhancement of the thermoelectric properties beyond a pure alloying effect. All of the investigated compositions exhibit maximal dimensionless figure of merit, ZT, values beyond 1, with the extraordinary value of 2.1 found for the 5% Bi2Te3 doped-Ge0.87Pb0.13Te composition, considered as among the highest ever reported. PMID- 25133860 TI - Walking Workstation Use Reduces Ambulatory Blood Pressure in Adults With Prehypertension. AB - BACKGROUND: The acute effect of low-intensity walking on blood pressure (BP) is unclear. PURPOSE: To determine if the acute use of a walking workstation reduces ambulatory blood pressure (ABP) in prehypertensive men and women. METHODS: Ten prehypertensive adults participated in a randomized, cross-over study that included a control workday and a walking workstation workday. ABP was measured for 7 hour during the workday and for 6 hour after work. RESULTS: Both systolic BP (SBP) (134 +/- 14 vs. 137 +/- 16 mmHg; P = .027) and diastolic BP (DBP) (79 +/ 10 vs. 82 +/- 12 mmHg; P = .001) were lower on the walking workstation day. Postwork hours (4:00 PM-10:00 PM), SBP (129 +/- 13 vs. 133 +/- 14 mmHg; P = .008), and DBP (74 +/- 11 vs. 78 +/- 13 mmHg; P = .001) were also lower on the walking workstation day. DBP load was significantly lower during the walking workstation day, with only 14% of the readings above 90 mmHg compared with 22% of the control day readings (P = .037). CONCLUSION: Accumulation of very-light intensity physical activity (~2 METs) over the course of a single work day using a walking workstation may reduce BP burden in prehypertensive individuals. PMID- 25133861 TI - Automatic generic registration of mass spectrometry imaging data to histology using nonlinear stochastic embedding. AB - The combination of mass spectrometry imaging and histology has proven a powerful approach for obtaining molecular signatures from specific cells/tissues of interest, whether to identify biomolecular changes associated with specific histopathological entities or to determine the amount of a drug in specific organs/compartments. Currently there is no software that is able to explicitly register mass spectrometry imaging data spanning different ionization techniques or mass analyzers. Accordingly, the full capabilities of mass spectrometry imaging are at present underexploited. Here we present a fully automated generic approach for registering mass spectrometry imaging data to histology and demonstrate its capabilities for multiple mass analyzers, multiple ionization sources, and multiple tissue types. PMID- 25133862 TI - Management of Hodgkin's lymphoma with midbrain involvement: A case report and review of literature. AB - Introduction Primary central nervous system (CNS) involvement of Hodgkin's lymphoma is very uncommon. There are only a few previous reports of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS concurrently with systemic disease. Case presentation A 12-year-old boy with a history of painless left inguinal swelling and acute diplopia. There was an intensely enhancing lesion in the right midbrain on magnetic resonance imaging. The patient was diagnosed with stage IV Hodgkin's lymphoma of nodular lymphocyte predominance type by routine microscopy and immunohistochemistry of left inguinal lymph node biopsy with computed tomography-assisted staging. It was planned to treat him with six cycles of chemotherapy with intrathecal methotrexate, followed by radiotherapy to the CNS lesions. After two cycles of chemotherapy, the patient entered complete remission of all lesions including the CNS lesion documented by the positron emission tomography scan. Conclusion We are describing the course of this rare presentation of Hodgkin's lymphoma of nodular lymphocyte predominant histology involving the CNS and clinical challenge in its diagnosis and management of this case. PMID- 25133864 TI - High-temperature, high-pressure hydrothermal synthesis, characterization, and structural relationships of layered uranyl arsenates. AB - Five new uranyl arsenates, Na14[(UO2)5(AsO4)8].2H2O (1), K6[(UO2)5O5(AsO4)2] (2a), K4[(UO2)3O2(AsO4)2] (2b), Rb4[(UO2)3O2(AsO4)2] (3), and Cs6[(UO2)5O2(AsO4)4] (4), were synthesized by high-temperature, high-pressure hydrothermal reactions at about 560 degrees C and 1440 bar and were characterized by single-crystal X-ray diffraction, thermogravimetric analysis, and photoluminescence spectroscopy. Crystal data for compound 1: triclinic, P1, a = 7.0005(3) A, b = 12.1324(4) A, c = 13.7428(5) A, alpha = 64.175(2) degrees , beta = 89.092(2) degrees , gamma = 85.548(2) degrees , V = 1047.26(7) A(3), Z = 1, R1 = 0.0185; compound 2a: monoclinic, P21/c, a = 6.8615(3) A, b = 24.702(1) A, c = 7.1269(3) A, beta = 98.749(2) degrees , V = 1193.89(9) A(3), Z = 2, R1 = 0.0225; compound 2b: monoclinic, P21/c, a = 6.7852(3) A, b = 17.3640(8) A, c = 7.1151(3) A, beta = 98.801(3) degrees , V = 828.42(6) A(3), Z = 2, R1 = 0.0269; compound 3: monoclinic, P21/m, a = 6.9783(3) A, b = 17.4513(8) A, c = 7.0867(3) A, beta = 90.808(3) degrees , V = 862.94(7) A(3), Z = 2, R1 = 0.0269; compound 4: triclinic, P1, a = 7.7628(3) A, b = 9.3324(4) A, c = 11.9336(4) A, alpha = 75.611(2) degrees , beta = 73.136(2) degrees , gamma = 86.329(2) degrees , V = 801.37(5) A(3), Z = 1, R1 = 0.0336. The five compounds have layer structures consisting of uranyl square, pentagonal, and hexagonal bipyramids as well as AsO4 tetrahedra. Compound 1 contains chains of discrete uranyl square and pentagonal bipyramids, 2a contains three-polyhedron-wide ribbons of edge- and corner-sharing uranyl square and pentagonal bipyramids, 2b and 3 contain dimers of edge-shairing pentagonal bipyramids that share edges with hexagonal bipyramids to form chains, and 4 contains one-polyhedron-wide zigzag chains of edge-sharing uranyl polyhedra. The double sheet structure of 1 is new, but the chain topology has been observed in an organically templated uranyl sulfate. Compound 2b is a new geometrical isomer of the phosphuranylite group. The sheet anion topologies of 2a and 4 can be obtained by splitting the beta-U3O8-type sheet into complex chains and connecting the chains by arsenates. PMID- 25133865 TI - Biopolymer-based structuring of liquid oil into soft solids and oleogels using water-continuous emulsions as templates. AB - Physical trapping of a hydrophobic liquid oil in a matrix of water-soluble biopolymers was achieved using a facile two-step process by first formulating a surfactant-free oil-in-water emulsion stabilized by biopolymers (a protein and a polysaccharide) followed by complete removal of the water phase (by either high- or low-temperature drying of the emulsion) resulting in structured solid systems containing a high concentration of liquid oil (above 97 wt %). The microstructure of these systems was revealed by confocal and cryo-scanning electron microscopy, and the effect of biopolymer concentrations on the consistency of emulsions as well as the dried product was evaluated using a combination of small-amplitude oscillatory shear rheometry and large deformation fracture studies. The oleogel prepared by shearing the dried product showed a high gel strength as well as a certain degree of thixotropic recovery even at high temperatures. Moreover, the reversibility of the process was demonstrated by shearing the dried product in the presence of water to obtain reconstituted emulsions with rheological properties comparable to those of the fresh emulsion. PMID- 25133863 TI - Infection management and multidrug-resistant organisms in nursing home residents with advanced dementia. AB - IMPORTANCE: Infection management in advanced dementia has important implications for (1) providing high-quality care to patients near the end of life and (2) minimizing the public health threat posed by the emergence of multidrug-resistant organisms (MDROs). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 362 residents with advanced dementia and their health care proxies in 35 Boston area nursing homes for up to 12 months. MAIN OUTCOMES AND MEASURES: Data were collected to characterize suspected infections, use of antimicrobial agents (antimicrobials), clinician counseling of proxies about antimicrobials, proxy preference for the goals of care, and colonization with MDROs (methicillin resistant Staphylococcus aureus, vancomycin-resistant enterococci, and multidrug resistant gram-negative bacteria). Main outcomes were (1) proportion of suspected infections treated with antimicrobials that met minimum clinical criteria to initiate antimicrobial treatment based on consensus guidelines and (2) cumulative incidence of MDRO acquisition among noncolonized residents at baseline. RESULTS: The cohort experienced 496 suspected infections; 72.4% were treated with antimicrobials, most commonly quinolones (39.8%) and third- or fourth-generation cephalosporins (20.6%). At baseline, 94.8% of proxies stated that comfort was the primary goal of care, and 37.8% received counseling from clinicians about antimicrobial use. Minimum clinical criteria supporting antimicrobial treatment initiation were present for 44.0% of treated episodes and were more likely when proxies were counseled about antimicrobial use (adjusted odds ratio, 1.42; 95% CI, 1.08-1.86) and when the infection source was not the urinary tract (referent). Among noncolonized residents at baseline, the cumulative incidence of MDRO acquisition at 1 year was 48%. Acquisition was associated with exposure (>1 day) to quinolones (adjusted hazard ratio [AHR], 1.89; 95% CI, 1.28-2.81) and third- or fourth-generation cephalosporins (AHR, 1.57; 95% CI, 1.04-2.40). CONCLUSIONS AND RELEVANCE: Antimicrobials are prescribed for most suspected infections in advanced dementia but often in the absence of minimum clinical criteria to support their use. Colonization with MDROs is extensive in nursing homes and is associated with exposure to quinolones and third- and fourth generation cephalosporins. A more judicious approach to infection management may reduce unnecessary treatment in these frail patients, who most often have comfort as their primary goal of care, and the public health threat of MDRO emergence. PMID- 25133866 TI - Examining the Relationship Between Physical Activity Intensity and Adiposity in Young Women. AB - BACKGROUND: The purpose of this study was to assess the relationship between intensity of physical activity (PA) and body composition in 343 young women. METHODS: Physical activity was objectively measured using accelerometers worn for 7 days in women 17 to 25 years. Body composition was assessed using the BOD POD. RESULTS: Young women who spent less than 30 minutes a week performing vigorous PA had significantly higher body fat percentages than women who performed more than 30 minutes of vigorous PA per week (F = 4.54, P = .0113). Young women who spent less than 30 minutes per day in moderate to vigorous PA (MVPA) had significantly higher body fat percentages than those who obtained more than 30 minutes per day of MVPA (F = 7.47, P = .0066). Accumulating more than 90 minutes of MVPA per day was associated with the lowest percent body fat. For every 10 minutes spent in MVPA per day, the odds of having a body fat percentage above 32% decreased by 29% (P = .0002). CONCLUSION: Vigorous PA and MVPA are associated with lower adiposity. Young women should be encouraged to accumulate at least 30 minutes of MVPA per day, however getting more than 90 minutes a day is predictive of even lower levels of adiposity. PMID- 25133869 TI - Nine hundred. PMID- 25133868 TI - Cardiac rehabilitation use among veterans with ischemic heart disease. PMID- 25133870 TI - Cognitive profiles of elder adult protective services clients living in squalor. AB - The purpose of this study was to determine whether squalor-dwelling Adult Protective Services (APS) clients were more cognitively impaired than non-squalor dwelling APS clients referred for decision-making capacity assessments. The authors performed a retrospective medical record review of neuropsychological and demographic data gathered during decisional capacity assessments. Squalor dwelling was defined by unsanitary living conditions that posed a danger to the occupant's health or safety. Mean neuropsychological test scores were compared between squalor-dwelling (n = 50) and non-squalor-dwelling (n = 180) subjects. Squalor-dwelling clients were significantly younger than non-squalor-dwelling clients. There were no distribution differences among gender, education, race, or rural-dwelling status. Although both groups performed poorly on each neuropsychological measure, squalor dwellers demonstrated better memory and general cognitive performance. Cognition, depression, gender, race, education, dementia diagnosis, and rural-dwelling status seem insufficient to explain squalor-dwelling behaviors. Other biological and psychosocial variables should be considered. PMID- 25133872 TI - Fe-catalyzed direct dithioacetalization of aldehydes with 2-chloro-1,3-dithiane. AB - Present methods to synthesize 1,3-dithiane molecules require either harsh reaction conditions or highly specialized reagents. We have developed a catalytic dithioacetalization process that directly gains access to the corresponding 1,3 dithianes using aldehydes and 2-chloro-1,3-dithiane in a highly efficient manner. This methodology is beneficial due to mildness of the reaction conditions, and the dithioacetaliation process results in good to excellent yields by using 15 mol % of an iron catalyst. PMID- 25133871 TI - Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: a population-based longitudinal study. AB - IMPORTANCE: Longitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear. OBJECTIVE: To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis. DESIGN, SETTING, AND PARTICIPANTS: The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospective general population birth cohort study based in Avon County, England. We have studied a subsample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessments. MEASUREMENT OF EXPOSURE: Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years. MAIN OUTCOMES AND MEASURES: Participants were assessed at age 18 years. Depression was measured using the Clinical Interview Schedule-Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ), thus allowing internal replication; psychotic experiences (PEs) and psychotic disorder were measured by a semistructured interview. RESULTS: After adjusting for sex, age, body mass index, ethnicity, social class, past psychological and behavioral problems, and maternal postpartum depression, participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55; 95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner. CONCLUSIONS AND RELEVANCE: Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood. Inflammatory pathways may provide important new intervention and prevention targets for these disorders. Inflammation might explain the high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia. PMID- 25133873 TI - Distributed polarizability models for imidazolium-based ionic liquids. AB - Quantum chemical calculations are used to derive distributed polarizability models sufficiently accurate and compact to be used in classical molecular dynamics simulations of imidazolium-based room temperature ionic liquids. Two distributed polarizability models are fitted to reproduce the induction energy of three imidazolium cations (1,3-dimethyl-, 1-ethyl-3-methyl-, and 1-butyl-3 methylimidazolium) and four anions (tetrafluoroborate, hexafluorophosphate, nitrate, and thiocyanate) polarized by a point charge located successively on a grid of surrounding points. The first model includes charge-flow polarizabilities between first-neighbor atoms and isotropic dipolar polarizability on all atoms (except H), while the second model includes anisotropic dipolar polarizabilities on all atoms (except H). For the imidazolium cations, particular attention is given to the transferability of the distributed polarizability sets. The molecular polarizability and its anisotropy rebuilt by the distributed models are found to be in good agreement with the exact ab initio values for the three cations and 23 additional conformers of 1-ethyl-3-methyl-, 1-butyl-3-methyl-, 1 pentyl-3-methyl-, and 1-hexyl-3-methylimidazolium cations. PMID- 25133875 TI - A jogged dislocation governed strengthening mechanism in nanotwinned metals. AB - Atomistic simulations reveal a new and unique strengthening mechanism in nanotwinned metals governed by the collective motion of multiple necklace-like extended jogged dislocations. This mechanism prevails in a columnar-grained nanotwinned metal subject to an external stress parallel to the twin planes, provided the twin boundary spacing falls below a critical value. A theoretical model based on the depinning of unit jogs on twin planes is proposed to determine the flow stress associated with this deformation mechanism and is shown to be in agreement with atomistic simulations. PMID- 25133874 TI - Impaired cerebrovascular reactivity in multiple sclerosis. AB - IMPORTANCE: Cerebrovascular reactivity (CVR) is an inherent indicator of the dilatory capacity of cerebral arterioles for a vasomotor stimulus for maintaining a spontaneous and instant increase of cerebral blood flow (CBF) in response to neural activation. The integrity of this mechanism is essential to preserving healthy neurovascular coupling; however, to our knowledge, no studies have investigated whether there are CVR abnormalities in multiple sclerosis (MS). OBJECTIVE: To use hypercapnic perfusion magnetic resonance imaging to assess CVR impairment in patients with MS. DESIGN, SETTING, AND PARTICIPANTS: A total of 19 healthy volunteers and 19 patients with MS underwent perfusion magnetic resonance imaging based on pseudocontinuous arterial spin labeling to measure CBF at normocapnia (ie, breathing room air) and hypercapnia. The hypercapnia condition is achieved by breathing 5% carbon dioxide gas mixture, which is a potent vasodilator causing an increase of CBF. MAIN OUTCOMES AND MEASURES: Cerebrovascular reactivity was calculated as the percent increase of normocapnic to hypercapnic CBF normalized by the change in end-tidal carbon dioxide, which was recorded during both conditions. Group analysis was performed for regional and global CVR comparison between patients and controls. Regression analysis was also performed between CVR values, lesion load, and brain atrophy measures in patients with MS. RESULTS: A significant decrease of mean (SD) global gray matter CVR was found in patients with MS (3.56 [0.81]) compared with healthy controls (5.08 [1.56]; P = .001). Voxel-by-voxel analysis showed diffuse reduction of CVR in multiple regions of patients with MS. There was a significant negative correlation between gray matter CVR and lesion volume (R = 0.6, P = .004) and a significant positive correlation between global gray matter CVR and gray matter atrophy index (R = 0.5, P = .03). CONCLUSIONS AND RELEVANCE: Our quantitative imaging findings suggest impairment in functional cerebrovascular pathophysiology, by measuring a diffuse decrease in CVR, which may be the underlying cause of neurodegeneration in MS. PMID- 25133877 TI - Development of a rapid capture-cum-detection method for Escherichia coli O157 from apple juice comprising nano-immunomagnetic separation in tandem with surface enhanced Raman scattering. AB - A combined capture and detection method comprising of nano-immunomagnetic separation (NIMS) and surface enhanced Raman spectroscopy (SERS) was developed to detect Escherichia coli O157 from liquid media including apple juice. The capture antibodies (cAbs) were immobilized on magnetite-gold (Fe3O4/Au) magnetic nanoparticles (MNPs) which were used for separation and concentration of the E. coli O157 cells from model liquid food matrix. The capture efficiency (CE) for E. coli O157 using MNP was found to be approximately 84-94%. No cross reactivity was observed with background non-target organisms. There was a significant difference in the mean CE of bacteria captured by MNP and commercially sourced immunomagnetic microbeads (p<0.05). For the detection of target pathogen, SERS labels were prepared by conjugating gold nanoparticles with Raman reporter molecules and the detector antibody (dAb). Au-Raman label-dAb was interacted with gold coated MNP-cAb-E. coli O157 complex. The ability of this immunoassay to detect E. coli O157 in apple juice was investigated. We have successfully applied the synthesized Fe3O4/Au nanoclusters to E. coli O157 detection in apple juice using the SERS method. The lowest detectable bacterial cell concentration in apple juice was 10(2)CFU/mL with a total analysis time of less than an hour. This method presents a convenient way of preconcentration, separation, and detection of low levels of target pathogen from liquid food matrix. PMID- 25133876 TI - Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid responsive asthma. AB - RATIONALE: Activation of type 2 cytokine pathways plays a central role in a large subset of subjects with asthma. Th2-high and Th2-low asthma have distinct clinical, pathologic, and molecular phenotypes and respond differently to therapy. The factors that initiate type 2 responses in some subjects with asthma are unknown. OBJECTIVES: To determine whether expression of epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin are associated with type 2 responses and predict response to inhaled corticosteroid (ICS) in asthma. METHODS: We analyzed pulmonary function tests, blood, and bronchoscopic biopsies from 21 healthy control subjects and 43 subjects with asthma. Subjects with asthma underwent an 8-week treatment with inhaled budesonide. MEASUREMENTS AND MAIN RESULTS: Epithelial expression of IL-25, but not IL-33 or thymic stromal lymphopoietin, was increased in a subset of subjects with asthma. The IL-25-high subset had greater airway hyperresponsiveness, more airway and blood eosinophils, higher serum IgE, more subepithelial thickening, and higher expression of Th2 signature genes. ICS improved FEV1 and hyperresponsiveness in the IL-25-high but not the IL-25-low subset. Plasma IL-25 levels correlated with epithelial IL-25 expression, airway eosinophilia, and beneficial responses to ICS treatment. CONCLUSIONS: IL-25 measurements identify two subsets of subjects with distinct asthma phenotypes and different responses to ICS. Because IL-25 has a major role in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a key determinant of type 2 response activation in asthma. Plasma IL-25 level reflects airway IL-25/type 2 response activation and may be useful for predicting responses to asthma therapy. PMID- 25133878 TI - The contribution of the Israeli trauma system to the survival of road traffic casualties. AB - BACKGROUND: According to the World Health Organization, over one million people die annually from traffic crashes, in which over half are pedestrians, bicycle riders and two-wheel motor vehicles. In Israel, during the last decade, mortality from traffic crashes has decreased from 636 in 1998 to 288 in 2011. Professionals attribute the decrease in mortality to enforcement, improved infrastructure and roads and behavioral changes among road users, while no credit is given to the trauma system. Trauma systems which care for severe and critical casualties improve the injury outcomes and reduce mortality among road casualties. GOALS: 1) To evaluate the contribution of the Israeli Health System, especially the trauma system, on the reduction in mortality among traffic casualties. 2) To evaluate the chance of survival among hospitalized traffic casualties, according to age, gender, injury severity and type of road user. METHODS: A retrospective study based on the National Trauma Registry, 1998-2011, including hospitalization data from eight hospitals. OUTCOMES: During the study period, the Trauma Registry included 262,947 hospitalized trauma patients, of which 25.3% were due to a road accident. During the study period, a 25% reduction in traffic related mortality was reported, from 3.6% in 1998 to 2.7% in 2011. Among severe and critical (ISS 16+) casualties the reduction in mortality rates was even more significant, 41%; from 18.6% in 1998 to 11.0% in 2011. Among severe and critical pedestrian injuries, a 44% decrease was reported (from 29.1% in 1998 to 16.2% in 2011) and a 65% reduction among bicycle injuries. During the study period, the risk of mortality decreased by over 50% from 1998 to 2011 (OR 0.44 95% 0.33-0.59. In addition, a simulation was conducted to determine the impact of the trauma system on mortality of hospitalized road casualties. Presuming that the mortality rate remained constant at 18.6% and without any improvement in the trauma system, in 2011 there would have been 182 in-hospital deaths compared to the actual 108 traffic related deaths. A 41% difference was noted between the actual number of deaths and the expected number. CONCLUSIONS: This study clearly shows that without any improvement in the health system, specifically the trauma system, the number of traffic deaths would be considerably greater. Although the health system has a significant contribution on reducing mortality, it does not receive the appropriate acknowledgment or resources for its proportion in the fight against traffic accidents. PMID- 25133879 TI - A direct biocombinatorial strategy toward next generation, mussel-glue inspired saltwater adhesives. AB - Biological materials exhibit remarkable, purpose-adapted properties that provide a source of inspiration for designing new materials to meet the requirements of future applications. For instance, marine mussels are able to attach to a broad spectrum of hard surfaces under hostile conditions. Controlling wet-adhesion of synthetic macromolecules by analogue processes promises to strongly impact materials sciences by offering advanced coatings, adhesives, and glues. The de novo design of macromolecules to mimic complex aspects of mussel adhesion still constitutes a challenge. Phage display allows material scientists to design specifically interacting molecules with tailored affinity to material surfaces. Here, we report on the integration of enzymatic processing steps into phage display biopanning to expand the biocombinatorial procedure and enable the direct selection of enzymatically activable peptide adhesion domains. Adsorption isotherms and single molecule force spectroscopy show that those de novo peptides mimic complex aspects of bioadhesion, such as enzymatic activation (by tyrosinase), the switchability from weak to strong binders, and adsorption under hostile saltwater conditions. Furthermore, peptide-poly(ethylene oxide) conjugates are synthesized to generate protective coatings, which possess anti fouling properties and suppress irreversible interactions with blood-plasma protein cocktails. The extended phage display procedure provides a generic way to non-natural peptide adhesion domains, which not only mimic nature but also improve biological sequence sections extractable from mussel-glue proteins. The de novo peptides manage to combine several tasks in a minimal 12-mer sequence and thus pave the way to overcome major challenges of technical wet glues. PMID- 25133880 TI - Tigers and snakes in neuro-ophthalmology. PMID- 25133881 TI - Cerebrospinal fluid pressure in adults. AB - BACKGROUND: Lumbar puncture (LP) is a widely-used investigative procedure. It allows relatively non-invasive measurement of intracranial pressure (ICP) which may have a significant impact on diagnosis and/or patient management. Over the years there has been considerable discussion about various aspects of the procedure, including what constitutes a normal opening pressure, what factors might influence this, and how LP is best performed. EVIDENCE ACQUISITION: A review of the literature was carried out by searching PubMed and Medline, scanning relevant medical journals for recent publications, and carrying out secondary referencing and contacting other clinicians, where appropriate. RESULTS: The normal range of ICP measured by LP in adults in a typical clinical setting should now be regarded as 6 to 25 cmH2O (95% confidence intervals), with a population mean of about 18 cmH2O. There is, however, considerable variability: some normal individuals have pressures of 30 cmH2O (or, occasionally, even higher) meaning that pressure measurements must be interpreted in the clinical context. CONCLUSIONS: This article aims to provide the practicing neuro ophthalmologist with up-to-date information about the ways in which various factors can influence pressure measurements obtained at LP. PMID- 25133882 TI - Interpretation of lumbar puncture opening pressure measurements in children. AB - BACKGROUND: Understanding the reference range of cerebrospinal fluid opening pressure (CSFOP) in children is essential to the diagnosis of elevated intracranial pressure. Recent studies have highlighted several clinical elements that need to be considered when interpreting CSFOP measures. EVIDENCE ACQUISITION: This review and recommendations are based on peer-reviewed literature, primarily from the past decade, as well as the author's clinical and research experience. RESULTS: CSFOP measures <=28 cm H2O can be considered "normal" for most children. The patient's depth of sedation, body mass index, and sedation medication can sometimes result in small increases in CSFOP. Patient age and leg position (flexed vs extended) in the lateral decubitus position do not seem to significantly impact CSFOP measures. CONCLUSIONS: The threshold of a normal CSFOP should not be interpreted in isolation, but instead, in concert with other clinical and examination findings to help the physician make a well informed assessment of whether a child has elevated intracranial pressure. PMID- 25133884 TI - A 16-year-old boy with a suprasellar mass. PMID- 25133883 TI - Noninvasive assessment of cerebrospinal fluid pressure. AB - Measurement of intracranial pressure (ICP) is critical for the evaluation and management of many neurological and neurosurgical conditions. The invasiveness of ICP measurement limits the frequency with which ICP can be evaluated, hampering the clinical care of patients with ICP disorders. Thus, there has been substantial interest in developing noninvasive methods for the assessment of ICP. Numerous approaches have been applied to the problem, although none seems to represent a complete solution. The goal of this review is to familiarize the reader with the currently available methods to noninvasively evaluate ICP. PMID- 25133885 TI - Do patients with neurologically isolated ocular motor cranial nerve palsies require prompt neuroimaging? PMID- 25133887 TI - The role of the American Academy of Family Physicians in supporting breastfeeding. PMID- 25133888 TI - Re: Marchington JM, Burd GP. Author attitudes to professional medical writing support. Curr Med Res Opin 2014 Jul 9:1-6. PMID- 25133890 TI - Metazoan symbionts of the yellow clam, Mesodesma donacium (Bivalvia), in southern Chile: geographical variations. AB - Mesodesma donacium is a dominant species on sandy beaches along the Chilean coast. However, the only previous parasite records for this species were obtained for the northern Chilean coast (20 degrees S-33 degrees S), which dealt with cestodes, polychaetes, and copepods. In this study, the symbiotic fauna of M. donacium in its southern distributional range is reported, and the geographical variations in the occurrence of this fauna are evaluated. A total of 565 individuals of M. donacium were captured by local fishermen from 5 localities: Mehuin (MEH) (39 degrees 26' S), Carelmapu (CAR) (41 degrees 44' S), Ancud (ANC) (41 degrees 53' S), Cucao (CUC) (42 degrees 35' S), and Quellon (QUE) (43 degrees 24' S), covering a total distance of 450 km. To collect metazoan symbionts, the valves, mantle, gills, gonad, and digestive gland of each specimen of yellow clam were examined, and symbiont identifications were made via morphological and genetic analyses. The prevalence and mean intensity of infestation were calculated for each symbiotic species. Univariate and multivariate analyses were performed to evaluate the differences in symbiotic load between localities. Seven metazoan symbiotic species were recorded. The most abundant species were Paranthessius mesodesmatis, Monorchiidae gen. sp., and Paravortex sp. The copepod P. mesodesmatis and metacercaria Monorchiidae gen. sp. showed a high prevalence in all localities, but their intensity of infection varied among localities. The turbellarian Paravortex sp. was most frequently associated with ANC and CUC. The digenean Sanguinicolidae gen. sp. was recorded only at CAR, and the polychaete Spionidae gen. sp. was recorded only at MEH. In its southern distributional range, M. donacium was characterized by an absence of cestodes. This absence can be explained by the absence of the definitive host. The local environmental conditions in the southern range of the host could explain the differences in symbiotic composition among localities. PMID- 25133889 TI - Carotid artery blood flow decreases after rapid head rotation in piglets. AB - Modification of cerebral perfusion pressure and cerebral blood flow (CBF) are crucial components of the therapies designed to reduce secondary damage after traumatic brain injury (TBI). Previously we documented a robust decrease in CBF after rapid sagittal head rotation in our well-validated animal model of diffuse TBI. Mechanisms responsible for this immediate (<10 min) and sustained (~24 h) reduction in CBF have not been explored. Because the carotid arteries are a major source of CBF, we hypothesized that blood flow through the carotid arteries (Q) and vessel diameter (D) would decrease after rapid nonimpact head rotation without cervical spine injury. Four-week-old (toddler) female piglets underwent rapid (<20 msec) sagittal head rotation without impact, previously shown to produce diffuse TBI with reductions in CBF. Ultrasonographic images of the bilateral carotid arteries were recorded at baseline (pre-injury), as well as immediately after head rotation and 15, 30, 45, and 60 min after injury. Diameter (D) and waveform velocity (V) were used to calculate blood flow (Q) through the carotid arteries using the equation Q=(0.25)piD(2)V. D, V, and Q were normalized to the pre-injury baseline values to obtain a relative change after injury in right and left carotid arteries. Three-way analysis of variance and post-hoc Tukey-Kramer analyses were used to assess statistical significance of injury, time, and side. The relative change in carotid artery diameter and flow was significantly decreased in injured animals in comparison with uninjured sham controls (p<0.0001 and p=0.0093, respectively) and did not vary with side (p>0.39). The average carotid blood velocity did not differ between sham and injured animals (p=0.91). These data suggest that a reduction in global CBF after rapid sagittal head rotation may be partially mediated by a reduction in carotid artery flow, via vasoconstriction. PMID- 25133891 TI - Good outcome of haploidentical hematopoietic SCT as a salvage therapy in children and adolescents with acquired severe aplastic anemia. AB - Haploidentical hematopoietic SCT (haplo-HSCT) is to be established in patients with acquired severe aplastic anemia (SAA) refractory to immunosuppressive therapy and lacking HLA-matched related or unrelated donors. Graft failure (GF) and GVHD have been major obstacles to HSCT. A total of 17 children and adolescents with SAA underwent haplo-HSCT in our center. The conditioning regimen consisted of BU, fludarabine, CY and anti-thymocyte globulin. All patients received cyclosporine, short-term MTX, mycophenolate mofetil and basiliximab for GVHD prophylaxis. Mesenchymal stem cells derived from unrelated umbilical cord were infused on day 1. Neutrophil engraftment was achieved in all 17 patients in a median time of 16 days (range 9-25 days). The median time of platelet engraftment was 22 days (range 9-95 days) in 16 patients. The cumulative incidence (CI) of II-IV acute GVHD (aGVHD) at day +100 was 30.53+/-11.12% and III IV aGVHD occurred in only one patient. The CI of chronic GVHD was 21.25+/-13.31%. Secondary GF with autologous hematopoiesis recovery occurred in one patient. The OS was 71.60+/-17.00% at a median follow-up of 362 (36-1321) days. These limited promising data suggest that haplo-HSCT is feasible as a salvage therapy for children and adolescents with refractory SAA who lack matched donors. PMID- 25133892 TI - Long-term remission after high-dose chemotherapy followed by auto-SCT as consolidation for intravascular large B-cell lymphoma. PMID- 25133894 TI - Risk factor analysis of posterior reversible encephalopathy syndrome after allogeneic hematopoietic SCT in children. PMID- 25133895 TI - A golden opportunity. PMID- 25133893 TI - Not too little, not too much-just right! (Better ways to give high dose melphalan). AB - Of the 13 286 autologous haematopoietic cell transplant procedures reported in the US in 2010-2012 for plasma cell disorders, 10 557 used single agent, high dose melphalan. Despite 30 years of clinical and pharmacokinetic (PK) experience with high-dose melphalan, and its continuing central role as cytoreductive therapy for large numbers of patients with myeloma, the pharmacodynamics and pharmacogenomics of melphalan are still in their infancy. The addition of protectant agents such as amifostine and palifermin allows dose escalation to 280 mg/m(2), but at these doses it is cardiac, rather than gut, toxicity that is dose limiting. Although combination with additional alkylating agents is feasible, the additional TRM may not be justified when so many post-consolidation therapies are available for myeloma patients. Current research should optimise the delivery of this single-agent chemotherapy. This includes the use of newer formulations and real-time PKs. These strategies may allow a safe and effective platform for adding synergistic novel therapies and provide a window of lymphodepletion for the addition of immunotherapies. PMID- 25133896 TI - Bortezomib/bendamustine/dexamethasone induced good PR in refractory relapse post auto-SCT with constitutive RAS activation due to V600E BRAF mutation. PMID- 25133897 TI - Tracheobronchomalacia after allogeneic BMT; pulmonary function test findings similar to those of bronchiolitis obliterans. PMID- 25133899 TI - Salt stress mitigation by seed priming with UV-C in lettuce plants: growth, antioxidant activity and phenolic compounds. AB - Seeds of Lactuca sativa L. 'Romaine' were subjected to priming treatments with UV C radiation at 0.85 or 3.42 kJ m(-2). Seedlings obtained from both primed (Pr) and non-primed (NPr) seeds were grown in an hydroponic culture system supplemented with 0 (control) or 100 mM NaCl. After 21 days of NaCl treatment, root and leaf biomass, root lengths, leaf numbers, and leaf surface area were measured. Ions (Na(+) and K(+)) accumulation was determined in roots and leaves. Total phenolic compound and flavonoid concentrations, as well as antioxidant and antiradical activities were measured in L. sativa leaves. Salt stress resulted in a lower increase in fresh weight of roots and leaves, which was more pronounced in roots than in leaves, due to reduced root elongation, leaf number and leaf expansion, as well as leaf thickness. The lower increase in fresh weight was accompanied by a restriction in tissue hydration and K(+) ion uptake, as well as an increase in Na(+) ion concentrations in all organs. These effects were mitigated in plants from the UV-C primed seeds. The mitigating effect of UV-C was more pronounced at 0.85 than at 3.42 kJ m(-2). Salt stress also resulted in an increase in total phenolic compounds and flavonoid concentrations and in the total antioxidant capacity in leaves. The highest diphenylpicrylhydrazyl radical (DPPH) scavenging activity was found in the leaves of plants from both Pr seeds. Our results suggest that plants grown from seed primed by exposure to moderate UV C radiation exhibited a higher tolerance to salinity stress. PMID- 25133898 TI - Sleep quality following hematopoietic stem cell transplantation: longitudinal trajectories and biobehavioral correlates. AB - The present study examined changes in sleep quality following hematopoietic stem cell transplantation (HSCT) and investigated associations with biobehavioral factors. Individuals undergoing HSCT for hematologic malignancies (N=228) completed measures of sleep quality and psychological symptoms pre-transplant and 1, 3, 6 and 12 months post transplant. Circulating inflammatory cytokines (IL-6, TNF-alpha) were also assessed. Sleep quality was poorest at 1 month post transplant, improving and remaining relatively stable after 3 months post transplant. However, approximately half of participants continued to experience significant sleep disturbance at 6 and 12 months post transplant. Mixed-effects linear regression models indicated that depression and anxiety were associated with poorer sleep quality, while psychological well-being was associated with better sleep. Higher circulating levels of IL-6 were also linked with poorer sleep. Subject-level fixed effects models demonstrated that among individual participants, changes in depression, anxiety and psychological well-being were associated with corresponding changes in sleep after covarying for the effects of time since transplant. Sleep disturbance was most severe when depression and anxiety were greatest and psychological well-being was lowest. Findings indicate that sleep disturbance is a persistent problem during the year following HSCT. Patients experiencing depression or anxiety and those with elevated inflammation may be at particular risk for poor sleep. PMID- 25133900 TI - Biomass-directed synthesis of 20 g high-quality boron nitride nanosheets for thermoconductive polymeric composites. AB - Electrically insulating boron nitride (BN) nanosheets possess thermal conductivity similar to and thermal and chemical stabilities superior to those of electrically conductive graphenes. Currently the production and application of BN nanosheets are rather limited due to the complexity of the BN binary compound growth, as opposed to massive graphene production. Here we have developed the original strategy "biomass-directed on-site synthesis" toward mass production of high-crystal-quality BN nanosheets. The strikingly effective, reliable, and high throughput (dozens of grams) synthesis is directed by diverse biomass sources through the carbothermal reduction of gaseous boron oxide species. The produced BN nanosheets are single crystalline, laterally large, and atomically thin. Additionally, they assemble themselves into the same macroscopic shapes peculiar to original biomasses. The nanosheets are further utilized for making thermoconductive and electrically insulating epoxy/BN composites with a 14-fold increase in thermal conductivity, which are envisaged to be particularly valuable for future high-performance electronic packaging materials. PMID- 25133901 TI - Beneficial health effects of Chios Gum Mastic and peroxisome proliferator activated receptors: indications of common mechanisms. AB - For thousands of years, Chios Gum Mastic (CGM), the resin produced by the trunk of Pistachia lentiscus var Chia, has been used for culinary and medicinal purposes and several therapeutic properties have been attributed to it. CGM has been used in traditional medicine of various nations in the eastern Mediterranean area. This survey was carried out to identify biological mechanisms that could explain traditional usage and recent pharmacological findings. We reviewed the related scientific literature available from the NCBI PUBMED database on CGM studies and on natural products showing peroxisome proliferator-activated receptor (PPAR) agonist effects. We investigated whether CGM qualifies as a PPAR modulator. A large number of studies demonstrate that CGM has antioxidant, anti inflammatory, hypolipidemic, and anticancer properties. Recently, the first evidence of CGM antidiabetic effect became known. CGM chemical composition has been extensively analyzed and the presence of several compounds, especially triterpenoids is well documented. Some of them, oleanonic acid, oleanolic acid, and gallic acid are considered to act as PPAR modulators. PPARs are nuclear receptors functioning as transcription factors and thereby controlling cellular functions at the level of gene expression. PPARs are involved in the pathways of significant diseases, such as metabolic syndrome, diabetes mellitus, dyslipidemia, inflammation, atheromatosis, and neoplasias, constituting a key target for pharmacological interventions. This article proposes that the synergistic action of some constituents of CGM on PPARs and more precisely on both PPARs isotypes-alpha and -gamma, may be one of the major biological mechanisms via which CGM exerts its multiple effects. PMID- 25133902 TI - How we treat our own: the experiences and characteristics of psychology trainees with disabilities. AB - OBJECTIVE: To better understand the characteristics and experiences of psychologists and trainees with disabilities. METHOD: An invitation to participate in a survey of psychologists and psychology trainees with disabilities was sent to professional listservs related to psychology and/or disability. Fifty-six trainees and psychologists with doctoral training in clinical, counseling, school, or rehabilitation psychology completed the survey. Over half (57.1%) were practicing psychologists and 42.9% were current trainees. The most commonly reported disabilities were physical, sensory, and chronic health. RESULTS: The majority of the participants reported experiencing disability-related discrimination during their training, and less than one third had received mentorship from psychologists with disabilities. Less than half of respondents disclosed their disability to a university disability services office, and many relied on informal accommodations alone. Most participants did not disclose their disability during the graduate school, internship, or postdoctoral application processes. CONCLUSIONS: Professional psychology programs and training sites should work to remove barriers and provide support for trainees with disabilities, especially during preinternship doctoral training. Programs should not expect disability services offices to provide all support for students with disabilities, especially support related to clinical training. PMID- 25133903 TI - Does slowed processing speed account for executive deficits in multiple sclerosis? Evidence from neuropsychological performance and structural neuroimaging. AB - OBJECTIVE: Executive deficits and slow processing speed (PS) are observed in persons with multiple sclerosis (MS). The question of whether executive deficits can be explained by slow PS was examined with neuropsychological measures and a neurostructural measure (brain atrophy). METHOD: Fifty MS patients were compared with 28 healthy controls (HCs) on tasks of executive functioning with and without a PS element (e.g., Trail Making Test and Wisconsin Card Sorting Test). RESULTS: The MS group performed worse than HCs on speeded tasks of executive function. However, after controlling for speed, group differences on executive tasks disappeared. There were also no group differences on executive tasks with no PS demands. The effect of disease progression on executive task performance was assessed in the MS group. Higher atrophy in MS participants was associated with greater deficits on speeded executive tasks, but this association disappeared when controlling for PS. There was no association between atrophy and performance on nonspeeded executive tasks. CONCLUSIONS: Our results support the notion that executive deficits in MS may be explained by slow PS. These findings highlight the role of slowed PS as a primary impairment underlying other cognitive functions. Disentangling the relative contribution of PS to executive function is an important step toward the development of appropriate rehabilitation strategies for persons with MS. PMID- 25133904 TI - Listeners' preference for computer-synthesized speech over natural speech of people with disabilities. AB - PURPOSE/OBJECTIVE: There are few controlled experimental studies that examine reactions to people with speech disabilities. We conducted 2 studies designed to examine participants' reactions to persuasive appeals delivered by people with physical disabilities and mild to moderate dysarthria. RESEARCH METHOD/DESIGN: Research participants watched video clips delivered by actors with bona fide disabilities and subsequently rated the argument, message, and the speaker. The first study (n = 165) employed a between-groups design that examined reactions to natural dysarthric speech, synthetic speech as entered into a keyboard by hand, and synthetic speech as entered into a keyboard with a headwand. The second study (n = 27) employed a within-groups design that examined how participants reacted to natural dysarthric speech versus synthetic speech as entered into a keyboard by hand. RESULTS: Both of these studies provide evidence that people rated the argument, message, and speaker more favorably when people with disabilities used synthetic speech than when they spoke in their natural voice. CONCLUSIONS/IMPLICATIONS: The implications are that although people react negatively to computer-synthesized speech, they prefer it to and find it more persuasive than the speech of people with disabilities. This appears to be the case even if the speech is only moderately impaired and is as intelligible as the synthetic speech. Hence, the decision to use synthetic speech versus natural speech can be further complicated by an understanding that even the intelligible speech of people with disabilities leads to more negative reactions than synthetic speech. PMID- 25133906 TI - Stability of vocational interests after recent spinal cord injury. AB - OBJECTIVE: We sought to identify the stability of vocational interests among persons with spinal cord injury (SCI) first assessed during inpatient rehabilitation. DESIGN: Initial assessments were completed during inpatient rehabilitation an average of 50 days after SCI onset (n = 521). Follow-up measures, collected by mail, were obtained an average of 16.6 months postinjury (n = 190) and 29.1 months postinjury (n = 296). Participants (n = 135) completed all 3 assessments. Participants completed the 1994 Strong Interest Inventory (Campbell, 1971; Harmon, Hansen, Borgen, & Hammer, 1994), Form T317, a 317-item measure of vocational interests. RESULTS: Comparison of scale means across 3 times of measurement indicated significant changes in 2 of 6 general occupational themes (GOT), 8 basic interest scales (BIS), and 2 special scales (leadership style, risk taking/adventure). With 1 exception, a linear trend indicating an increase in reported interests accounted for observed relationships. An age by time interaction occurred with 1 GOT and 3 BIS. The average stability coefficient was 0.61 for the GOT, 0.59 for the BIS, and 0.70 for the special scales. The average coefficients were somewhat lower for the oldest participants. CONCLUSION: Interests do not appear to be static when first measured during inpatient rehabilitation after SCI. Rather, they evolve with average increases on select themes more compatible with the limitations of SCI. Stability coefficients suggest that interests are likely to change more than indicated in earlier studies. PMID- 25133905 TI - Effort in acute traumatic brain injury: considering more than pass/fail. AB - PURPOSE/OBJECTIVE: Performance validity is often conceptualized as a dichotomous process. Effort likely lies on a continuum, however, and psychologists' tendency to rely on pass/fail descriptors of one's effort may not be the only approach. The current study aims to show that when performance validity is considered on a continuum, it may provide clinical information related to cognitive functioning. RESEARCH METHOD/DESIGN: Forty-four patients with moderate or severe traumatic brain injury were evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status upon their emergence from posttraumatic amnesia. From this data, previously developed effort index scores and "other cognitive functions" index scores were calculated. RESULTS: Performance on the effort index significantly accounted for the patients' performance on a cognitive composite score after considering education and severity of injury. CONCLUSIONS/IMPLICATIONS: Findings suggest that more in-depth analysis of validity test performance is beneficial to gauge a patient's level of effort and is important to consider when interpreting results and in treatment planning. PMID- 25133907 TI - Coping strategies and resources as predictors of psychosocial adaptation among people with spinal cord injury. AB - PURPOSE: The onset of a spinal cord injury (SCI) is accompanied by a massive amount of stress, on which professionals in the medical field focus attention and care. The subsequent cascade of psychological stressors related to SCI often receives lesser attention. When individuals experience new forms of stress, they typically respond with attempts to cope, which may or may not be adaptive in reducing their stress levels. The twofold purpose of this study was to investigate whether SCI survivors' use of coping resources (i.e., hope, sense of coherence) and coping strategies (e.g., engagement coping, seeking social support) influences their psychosocial adaptation, and whether their use of coping strategies moderates the effect of coping resources, after controlling for the influence of depression and anxiety, on psychosocial adaptation. DESIGN: This cross-sectional study involved a self-report survey of survivors of SCI. Inclusion criteria included: (a) being 18 years of age or older, (b) having received inpatient rehabilitation services following the SCI, and (c) not having traumatic head injury at the time of the SCI onset. PARTICIPANTS: The sample consisted of 95 individuals with SCI who received outpatient rehabilitation services at a center in the midsouthern United States. RESULTS: Results indicated that coping resources and coping strategies were significantly associated with psychosocial adaptation. Furthermore, engagement coping explained a significant portion of the variance in psychosocial adaptation both individually and as an interactive variable with the 2 coping resources of sense of coherence and hope. CONCLUSIONS: Findings indicate that both coping resources and strategies (especially engagement coping) are reliably linked to adaptation to SCI. The findings further suggest that engagement coping positively influences psychosocial adaptation even when coping resources are mostly absent. Other implications for the field of rehabilitation are briefly outlined. PMID- 25133915 TI - Symmetrized photoinitiated electron flow within the [myoglobin:cytochrome b5] complex on singlet and triplet time scales: energetics vs dynamics. AB - We report here that photoinitiated electron flow involving a metal-substituted (M = Mg, Zn) myoglobin (Mb) and its physiological partner protein, cytochrome b5 (cyt b5) can be "symmetrized": the [Mb:cyt b5] complex stabilized by three D/E -> K mutations on Mb (D44K/D60K/E85K, denoted MMb) exhibits both oxidative and reductive ET quenching of both the singlet and triplet photoexcited MMb states, the direction of flow being determined by the oxidation state of the cyt b5 partner. The first-excited singlet state of MMb ((1)MMb) undergoes ns-time scale reductive ET quenching by Fe(2+)cyt b5 as well as ns-time scale oxidative ET quenching by Fe(3+)cyt b5, both processes involving an ensemble of structures that do not interconvert on this time scale. Despite a large disparity in driving force favoring photooxidation of (1)MMb relative to photoreduction (delta( DeltaG(0)) ~ 0.4 eV, M = Mg; ~ 0.2 eV, M = Zn), for each M the average rate constants for the two reactions are the same within error, (1)k(f) > 10(8) s(-1). This surprising observation is explained by considering the driving-force dependence of the Franck-Condon factor in the Marcus equation. The triplet state of the myoglobin ((3)MMb) created by intersystem crossing from (1)MMb likewise undergoes reductive ET quenching by Fe(2+)cyt b5 as well as oxidative ET quenching by Fe(3+)cyt b5. As with singlet ET, the rate constants for oxidative ET quenching and reductive ET quenching on the triplet time scale are the same within error, (3)k(f) ~ 10(5) s(-1), but here the equivalence is attributable to gating by intracomplex conversion among a conformational ensemble. PMID- 25133916 TI - A false dichotomy? Mental illness and lone-actor terrorism. AB - We test whether significant differences in mental illness exist in a matched sample of lone- and group-based terrorists. We then test whether there are distinct behavioral differences between lone-actor terrorists with and without mental illness. We then stratify our sample across a range of diagnoses and again test whether significant differences exist. We conduct a series of bivariate, multivariate, and multinomial statistical tests using a unique dataset of 119 lone-actor terrorists and a matched sample of group-based terrorists. The odds of a lone-actor terrorist having a mental illness is 13.49 times higher than the odds of a group actor having a mental illness. Lone actors who were mentally ill were 18.07 times more likely to have a spouse or partner who was involved in a wider movement than those without a history of mental illness. Those with a mental illness were more likely to have a proximate upcoming life change, more likely to have been a recent victim of prejudice, and experienced proximate and chronic stress. The results identify behaviors and traits that security agencies can utilize to monitor and prevent lone-actor terrorism events. The correlated behaviors provide an image of how risk can crystalize within the individual offender and that our understanding of lone-actor terrorism should be multivariate in nature. PMID- 25133917 TI - Short-sighted confession decisions: the role of uncertain and delayed consequences. AB - Suspects have a propensity to focus on short-term contingencies, giving disproportionate weight to the proximal consequences that are delivered by police during an interrogation, and too little consideration to the distal (and often more severe) consequences that may be levied by the judicial system if they are convicted. In this research, the authors examined whether the perceived uncertainty and temporal distance of distal consequences contribute to this propensity. Using the repetitive question paradigm (Madon et al., 2012), participants (N = 209) were interviewed about 20 prior criminal and unethical behaviors and were required to admit or deny each one. Participants' denials and admissions were paired with both a proximal consequence and a distal consequence, respectively. Results indicated that the distal consequence had less impact on participants' admission decisions when it was uncertain and temporally remote. These results provide evidence that the perceived uncertainty and temporal distance of future punishment are key factors that lead suspects to confess to crimes in exchange for short-term gains. PMID- 25133919 TI - Selecting fillers on emotional appearance improves lineup identification accuracy. AB - Mock witnesses sometimes report using criminal stereotypes to identify a face from a lineup, a tendency known as criminal face bias. Faces are perceived as criminal-looking if they appear angry. We tested whether matching the emotional appearance of the fillers to an angry suspect can reduce criminal face bias. In Study 1, mock witnesses (n = 226) viewed lineups in which the suspect had an angry, happy, or neutral expression, and we varied whether the fillers matched the expression. An additional group of participants (n = 59) rated the faces on criminal and emotional appearance. As predicted, mock witnesses tended to identify suspects who appeared angrier and more criminal-looking than the fillers. This tendency was reduced when the lineup fillers matched the emotional appearance of the suspect. Study 2 extended the results, testing whether the emotional appearance of the suspect and fillers affects recognition memory. Participants (n = 1,983) studied faces and took a lineup test in which the emotional appearance of the target and fillers was varied between subjects. Discrimination accuracy was enhanced when the fillers matched an angry target's emotional appearance. We conclude that lineup member emotional appearance plays a critical role in the psychology of lineup identification. The fillers should match an angry suspect's emotional appearance to improve lineup identification accuracy. PMID- 25133918 TI - Criminogenic factors, psychotic symptoms, and incident arrests among people with serious mental illnesses under intensive outpatient treatment. AB - Although research robustly indicates that general or "criminogenic" factors predict various measures of recidivism, there is controversy about the extent to which these factors, versus untreated symptoms, lead to justice involvement for people with mental illnesses. Based on a sample of 183 people in intensive outpatient treatment followed for an average period of 34.5 months, the present study tested whether criminogenic factors (i.e., factor-analytically derived proxies of some of the "Central Eight"; Andrews & Bonta, 2010) and psychotic symptoms were independently associated with arrest. The study also compared the predictive utility of these domains. In the fully adjusted model, the antisocial subscale and male sex were associated with increased arrest rates, whereas psychosis and age were associated with decreased arrest rates. Criminogenic factors and psychotic symptoms had comparable predictive utility. We conclude that criminogenic factors-chiefly arrest history-and psychotic symptoms predict arrest rates. Both sets of variables appear useful for assessing risk of arrest among people with mental illnesses who are not under current correctional supervision. PMID- 25133920 TI - Examining the impact of sexism on evaluations of social scientific evidence in discrimination litigation. AB - The present 2 studies involved undergraduate participants and investigated whether various types of sexism and other correlated predictors, such as political conservatism and scientific discounting, can predict people's evaluations of social science research on sex stereotypes, sexism, and sex discrimination. In Study 1, participants high in hostile sexism, scientific discounting, and/or political conservatism were more critical of scientific studies that provided evidence for sexism than identical studies showing null results. Study 2 showed that participants high in modern sexism, hostile sexism, and political conservatism evaluated social scientific studies more negatively; in addition, assessments of social scientific evidence quality mediated the effect of modern sexism on admissibility ratings (b = -0.15, z = -4.16, p = .00). Overall, these results suggest that sexist beliefs can bias one's judgments of social scientific evidence. Future research should explore whether the same psychological processes operate for judges and jurors as they evaluate the admissibility of evidence and examine ways to attenuate the effect of sexism on evaluations. PMID- 25133921 TI - Reporting guidance for violence risk assessment predictive validity studies: the RAGEE Statement. AB - Available reporting guidelines for prognostic and diagnostic accuracy studies apply primarily to biological assessment and outcomes, overlooking behavioral issues with major public health and safety implications such as violence. The present study aimed to develop the first set of reporting guidance for predictive validity studies of violence risk assessments: the Risk Assessment Guidelines for the Evaluation of Efficacy (RAGEE) Statement. A systematic search of 8 electronic databases prior to September 2012 identified 279 reporting guidelines for prognostic and diagnostic accuracy studies. Unique items were extracted and modified to make them relevant to risk assessment. A 4-wave Delphi process involving a multidisciplinary team of 37 international experts resulted in a 50 item reporting checklist. The panelists endorsed the RAGEE Statement checklist as being highly satisfactory and as indicating study features that should be reported routinely in manuscripts. Use of these proposed standards has the potential to improve the quality of the risk assessment literature. PMID- 25133922 TI - First-principles study on doping effects of sodium in kesterite Cu2ZnSnS4. AB - A sodium impurity is inevitable for Cu2ZnSnS4 on a substrate of soda-lime glass during high-temperature processing. Recently, it was found that a sodium impurity could improve the photovoltaic properties of Cu2ZnSnS4-based thin film solar cells (including influencing crystallinity, affecting grain growth, increasing hole density, shifting the acceptor level closer to the conduction band, increasing carrier concentration, elongating minority carrier lifetime, and so on). Thus, sodium doping becomes an effective modification means for Cu2ZnSnS4 on the flexible substrate. However, there are some examples available in the literature that discuss the underlying physical mechanism. In the present work, the crystal structure, electronic structure, and optical properties of sodium occupying different lattice sites or interstitial sites of kesterite Cu2ZnSnS4 were systematically calculated by density functional theory within the GGA+U method. Na impurity favors occupation of the interstitial sites. If Na impurity occupies the cation lattice sites, the band gap of Cu2ZnSnS4 will be broadened, which is opposite to the situation of an Na impurity occupying the interstitial sites. The doping effects of Na in Cu2ZnSnS4 are mainly exhibited by the following aspects: energy band shifting, energy band broadening or narrowing, and effective mass of holes on the top of valence band reduction. The calculated results in the present work not only confirm experimental observationa in published articles but also provide an in-depth understanding of them. Thus, the findings could help to promote novel, high-efficiency Cu2ZnSnS4-based thin-film solar cells. PMID- 25133925 TI - Electroaddressing of ZnS quantum dots by codeposition with chitosan to construct fluorescent and patterned device surface. AB - Electroaddressing is an attractive method for triggering assembly of stimuli responsive biopolymers with exquisite spatiotemporal control, and it also offers a controllable means to concurrently assemble biological materials and nanoparticles for a diverse range of applications. Here, we demonstrate a novel method to construct fluorescent and patterned device surfaces by electroaddressing of quantum dots (QDs)/chitosan composite. First, the surfaces of ZnS QDs/chitosan composite on the electrodes are built by electrodeposition method. It is shown that the deposited surface displays clear fluorescence under UV light, and the fluorescence intensity of the surface can be controlled by electrodeposition conditions (e.g., deposition time). Furthermore, a variety of fluorescent patterns can be constructed by employing electrodes or substrates with various shapes. Specifically, taking advantage of the spatiotemporal selectivity of electroaddressing and the pH-responsive property of chitosan, we construct diverse fluorescent patterns by electroaddressing QDs/chitosan composite at the localized region. It is also found that the fluorescent patterns of QDs/chitosan composite have reproducibility. Thus, this work presents a convenient, versatile, and controllable method to construct fluorescent and patterned device surface by electroaddressing, which has promising applications in photoluminescence device, fluorescent and patterned coating, and nanocomposite biodevice. PMID- 25133926 TI - Breaking down number syntax: spared comprehension of multi-digit numbers in a patient with impaired digit-to-word conversion. AB - Can the meaning of two-digit Arabic numbers be accessed independently of their verbal-phonological representations? To answer this question we explored the number processing of ZN, an aphasic patient with a syntactic deficit in digit-to verbal transcoding, who could hardly read aloud two-digit numbers, but could read them as single digits ("four, two"). Neuropsychological examination showed that ZN's deficit was neither in the digit input nor in the phonological output processes, as he could copy and repeat two-digit numbers. His deficit thus lied in a central process that converts digits to abstract number words and sends this information to phonological retrieval processes. Crucially, in spite of this deficit in number transcoding, ZN's two-digit comprehension was spared in several ways: (1) he could calculate two-digit additions; (2) he showed good performance in a two-digit comparison task, and a continuous distance effect; and (3) his performance in a task of mapping numbers to positions on an unmarked number line showed a logarithmic (nonlinear) factor, indicating that he represented two-digit Arabic numbers as holistic two-digit quantities. Thus, at least these aspects of number comprehension can be performed without converting the two-digit number from digits to verbal representation. PMID- 25133927 TI - Decoding letter position in word reading. AB - A fundamental computation underlying visual word recognition is the ability to transform a set of letters into a visual word form. Neuropsychological data suggest that letter position within a word may be independently affected by brain damage, resulting in a dissociable subtype of peripheral dyslexia. Here we used functional magnetic resonance imaging and supervised machine learning techniques to classify letter position based on activation patterns evoked during reading Hebrew words. Across the entire brain, activity patterns in the left intraparietal sulcus provided the best classification accuracy (80%) with respect to letter position. Importantly, the same set of voxels that showed highest classification performance of letter position using one letter-of-interest also showed highest classification performance using a different letter-of-interest. A functional connectivity analysis revealed that activity in these voxels co-varied with activity in the Visual Word Form Area, confirming cross-talk between these regions during covert reading. The results converge with reports of patients with acquired letter position dyslexia, who suffer from left occipito-parietal lesions. These findings provide direct and novel evidence for the role of left IPS within the reading network in processing relative letter positions. PMID- 25133923 TI - Design, synthesis, and biological evaluation of (3R)-1,2,3,4-tetrahydro-7-hydroxy N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2 methylpropyl]-3-isoquinolinecarboxamide (JDTic) analogues: in vitro pharmacology and ADME profile. AB - JDTic analogues 4-15 which have the hydroxyl groups replaced with other groups were synthesized and their in vitro efficacy at the MU, delta, and kappa opioid receptors determined and compared to JDTic using [(35)S]GTPgammaS assays. Compounds 4, 5, 6, 13, 14, and 15 had Ke = 0.024, 0.01, 0.039, 0.02, 0.11, and 0.041 nM compared to the Ke = 0.02 nM for JDTic at the kappa receptor and were highly selective for the kappa receptor relative to the MU and delta opioid receptors. Unexpectedly, replacement of the 3-hydroxyl substituent of the 4-(3 hydroxyphenyl) group of JDTic with a H, F, or Cl substituent leads to potent and selective KOR antagonists. In vitro studies to determine various ADME properties combined with calculated TPSA, clogP, and logBB values suggests that the potent and selective kappa opioid receptors 4, 5, 13, and 14 deserve consideration for further development toward potential drugs for CNS disorders. PMID- 25133929 TI - Covalency of hydrogen bonds in solids revisited. AB - The covalent nature of short hydrogen bonds has been under debate for long. Here we show that the crystal orbital Hamilton population (COHP) bonding indicator gives new, complementary evidence of covalent hydrogen...acceptor interactions in the molecular solid state. PMID- 25133928 TI - Cystine stones: a single tertiary center experience. AB - OBJECTIVE: To analyze the epidemiological and clinical characteristics and therapeutic outcomes of patients with cystine stones and to compare them with the characteristics of patients with calcium oxalate stones. PATIENTS AND METHODS: We identified 30 patients with cystine stones who were consulted in our department from January 1972 until December 2013. These patients were matched and paired, based on age and gender, to 30 calcium oxalate stone formers who were diagnosed and treated in our department from January 2011 until December 2013. RESULTS: Cystine stones were significantly large in size (p<0.001) and most of them were found in the kidney (p=0.002). Patients with cystinuria had their first stone episode at an early age (p<0.001) compared with patients with calcium oxalate stones. No significant differences were observed regarding the frequency and the severity of symptoms. Both groups had similar visits per year in outpatient clinics, emergency room admissions, and episodes of febrile urinary tract infections. Cystine stone formers had undergone significantly higher number of procedures for stone removal (p<0.001). No statistical differences were found in the compliance rates between the groups. Patients with cystine stones had significantly higher serum creatinine levels (p=0.005). CONCLUSIONS: Cystine stones present in an earlier age and have the likelihood to be large in size. Patients with cystine stones undergo a greater number of procedures, and they have a greater risk to develop chronic renal impairment. PMID- 25133930 TI - Zinc blende versus wurtzite ZnS nanoparticles: control of the phase and optical properties by tetrabutylammonium hydroxide. AB - The influence of tetrabutylammonium hydroxide on the phase composition (cubic zinc blende versus hexagonal wurtzite) of ZnS nanoparticles was studied. The ZnS nanoparticles were prepared by a microwave-assisted solvothermal method, and the phase structure and optical properties along with the growth process of ZnS nanoparticles were studied. We report XRD, FE-SEM, EDXS, UV-vis and PL measurements, and first-principles calculations based on TDDFT methods in order to investigate the structural and electronic properties and the growth mechanism of ZnS nanostructures. The effects as well as the merits of microwave heating on the process and characteristics of the obtained ZnS nanostructures and their performance are reported. PMID- 25133931 TI - ALPPS: Short-term Outcome and Functional Changes in the Future Liver Remnant. PMID- 25133932 TI - Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes. AB - OBJECTIVE: To study the association between diabetes status, perioperative hyperglycemia, and adverse events in a statewide surgical cohort. BACKGROUND: Perioperative hyperglycemia may increase the risk of adverse events more significantly in patients without diabetes (NDM) than in those with diabetes (DM). METHODS: Using data from the Surgical Care and Outcomes Assessment Program, a cohort study (2010-2012) evaluated diabetes status, perioperative hyperglycemia, and composite adverse events in abdominal, vascular, and spine surgery at 53 hospitals in Washington State. RESULTS: Among 40,836 patients (mean age, 54 years; 53.6% women), 19% had diabetes; 47% underwent a perioperative blood glucose (BG) test, and of those, 18% had BG >=180 mg/dL. DM patients had a higher rate of adverse events (12% vs 9%, P < 0.001) than NDM patients. After adjustment, among NDM patients, those with hyperglycemia had an increased risk of adverse events compared with those with normal BG. Among NDM patients, there was a dose-response relationship between the level of BG and composite adverse events [odds ratio (OR), 1.3 for BG 125-180 (95% confidence interval (CI), 1.1-1.5); OR, 1.6 for BG >=180 (95% CI, 1.3-2.1)]. Conversely, hyperglycemic DM patients did not have an increased risk of adverse events, including those with a BG 180 or more (OR, 0.8; 95% CI, 0.6-1.0). NDM patients were less likely to receive insulin at each BG level. CONCLUSIONS: For NDM patients, but not DM patients, the risk of adverse events was linked to hyperglycemia. Underlying this paradoxical effect may be the underuse of insulin, but also that hyperglycemia indicates higher levels of stress in NDM patients than in DM patients. PMID- 25133933 TI - Coating and enhanced photocurrent of vertically aligned zinc oxide nanowire arrays with metal sulfide materials. AB - Hybrid nanostructures combining zinc oxide (ZnO) and a metal sulfide (MS) semiconductor are highly important for energy-related applications. Controlled filling and coating of vertically aligned ZnO nanowire arrays with different MS materials was achieved via the thermal decomposition approach of single-source precursors in the gas phase by using a simple atmospheric-pressure chemical vapor deposition system. Using different precursors allowed us to synthesize multicomponent structures such as nanowires coated with alloy shell or multishell structures. Herein, we present the synthesis and structural characterization of the different structures, as well as an electrochemical characterization and a photovoltaic response of the ZnO-CdS system, in which the resulting photocurrent upon illumination indicates charge separation at the interface. PMID- 25133935 TI - A pilot study of manual chronic partial exchange transfusion in children with sickle disease. AB - Objective Red cell exchange transfusion is frequently used in the management of patients with sickle cell disease (SCD) either electively or chronically to maintain hemoglobin S (HbS) <30%. The purpose of this retrospective study was to evaluate the results of manual chronic partial exchange transfusion (MCPET) on level of Hb and HbS, on iron load and on the need for chelation, on risk of immunization, monitoring transfusion-transmitted viral infection, and clinical outcome. Methods We reviewed the long-term effect of MCPET in 10 children (six men and four women) with SCD and evaluated the iron balance during a median follow-up of 20 months (range: 6-36) in which 248 exchanges were performed. Results The pre-exchange median Hb value was 9.5 g/dl (range: 7.7-10.9 g/dl) and the median post-exchange value was 9.4 g/dl (range: 8.4-11.1 g/dl).The majority of patients reached an HbS of <50% with a median HbS value of 40.04% (range: 30 54). At start of the MCPET program, the median ferritin was 439 ng/ml (range: 80 1704 ng/ml). In the final evaluation, the median value of ferritin was 531 ng/ml (range: 84-3840 ng/ml). The annual calculated iron balance was 0. 28 +/- 0.08 mg/kg/day. MCPET was well tolerated, and adverse effects were limited. Discussion MCPET in children with SCD is safe to prevent iron overload, and is effective and easy to use in our cohort. Conclusion Indication for chronic exchange blood transfusion is essential for patients with SCD with recurrent and frequent crises who do not respond to hydroxyurea. However, there is no consensual study for the period at which chronic transfusion can safely be stopped and further research in large population of patients with SCD will need to clarify this question. PMID- 25133934 TI - Development of BODIPY FL vindoline as a novel and high-affinity pregnane X receptor fluorescent probe. AB - The pregnane X receptor (PXR) regulates the metabolism and excretion of xenobiotics and endobiotics by regulating the expression of drug-metabolizing enzymes and transporters. The unique structure of PXR allows it to bind many drugs and drug leads, possibly causing undesired drug-drug interactions. Therefore, it is crucial to evaluate whether chemicals or drugs bind to PXR. Fluorescence-based assays are preferred because of their sensitivity and nonradioactive nature. On the basis of our previously characterized 4 (BODIPY FL vinblastine), a high-affinity PXR probe, we developed 20 (BODIPY FL vindoline) and showed that it is a novel and potent PXR fluorescent probe with Kd of 256 nM in a time-resolved fluorescence resonance energy transfer (TR-FRET) binding assay with PXR. By using 20 (BODIPY FL vindoline) in the PXR TR-FRET assay, we obtained a more than 7-fold signal-to-background ratio and high signal stability (signal was stable for at least 120 min, and Z'-factor > 0.85 from 30 to 240 min). The assay can tolerate DMSO up to 2%. This assay has been used to evaluate a panel of PXR ligands for their PXR-binding affinities. The performance of 20 (BODIPY FL vindoline) in the PXR TR-FRET assay makes it an ideal PXR fluorescent probe, and the newly developed PXR TR-FRET assay with 20 (BODIPY FL vindoline) as a fluorescent probe is suitable for high-throughput screening to identify PXR binding ligands. PMID- 25133936 TI - Urinary catheterization -- when good intentions go awry: a teachable moment. PMID- 25133937 TI - Surface complexation reaction for phase transfer of hydrophobic quantum dot from nonpolar to polar medium. AB - Chemical reaction between oleate-capped Zn(x)Cd(1-x)S quantum dots (Qdots) and 8 hydroxyquinoline (HQ) led to formation of a surface complex, which was accompanied by transfer of hydrophobic Qdots from nonpolar (hexane) to polar (water) medium with high efficiency. The stability of the complex on the surface was achieved via involvement of dangling sulfide bonds. Moreover, the transferred hydrophilic Qdots--herein called as quantum dot complex (QDC)--exhibited new and superior optical properties in comparison to bare inorganic complexes with retention of the dimension and core structure of the Qdots. Finally, the new and superior optical properties of water-soluble QDC make them potentially useful for biological--in addition to light emitting device (LED)--applications. PMID- 25133938 TI - A bird's eye view of anisatin induced convulsive seizures in brain by a (1)H NMR based metabolic approach. AB - Anisatin is the main convulsant component in plants of the genus Illicium, many of which are important spices or folk medicines. The neurotoxicity of anisatin has been widely investigated, mainly focusing on its action on the gamma-amino butyrate (GABA) system; however, little is known about the metabolic alterations that it causes. In this study, a NMR-based metabolomic approach was performed on the extracts of cortexes and cerebellums of mice administered with anisatin to explore the metabolic events associated with its intoxication. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed many differential metabolites that indicated metabolic disturbance in neurotransmission and neuromodulation (GABA, glutamate, glutamine, and taurine), stress of reactive oxygen species (ROS) (ascorbate, phosphatidylcholine, choline, and ethanolamine), energy metabolism (NAD(+)i.e., nicotinamide-adenine dinucleotide, lactate, citrate, fumarate, creatine/phosphocreatine, and creatinine), amino acid metabolism (leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, alanine, threonine, and glycine) and nucleic acid metabolism (NAD(+), nicotinamide/niacinamide, adenosine, and guanosine). This pilot metabolomic study on anisatin intoxication should help to develop a holistic view of convulsive seizures induced by anisatin, and provide a better understanding of the mechanisms. PMID- 25133939 TI - Implementing a graduate medical education campaign to reduce or eliminate potentially wasteful tests or procedures. PMID- 25133940 TI - Efficacy and safety of histamine-2 receptor antagonists. AB - IMPORTANCE: Histamine-2 receptor antagonists (H2RAs) are frequently used in the treatment of gastroesophageal reflux disease (GERD) in children; however, their efficacy and safety is questionable. OBJECTIVE: To systematically review the literature to assess the efficacy and safety of H2RAs in pediatric GERD. EVIDENCE REVIEW: PubMed, EMBASE, and the Cochrane database were searched for randomized clinical trials investigating the efficacy and safety of H2RAs in pediatric GERD. Two reviewers independently extracted data from the included articles. The quality of the evidence was assessed using the Grades of Recommendations, Assessment, Development, and Evaluation approach. When possible, infants and children were analyzed separately. FINDINGS: Eight studies with a total of 276 children (0-15 years of age) were included. Compared with the placebo, H2RAs were more effective in the reduction of symptoms in terms of histologic healing and increasing gastric pH and had a larger overall treatment effect. In infants, H2RAs were only more effective in terms of histologic healing. Comparing H2RAs with antacids, H2RAs were more effective in symptom reduction in only 1 study. H2RAs compared with proton pump inhibitors were not significantly different in any of the outcome measures. For safety analysis, data were not reported in a quantitative manner and for all outcomes, the quality of evidence was very low. CONCLUSIONS AND RELEVANCE: Evidence to support the efficacy and safety of H2RAs in infants and children is limited and of poor quality. Well-designed placebo controlled trials are needed before thorough conclusions can be drawn. PMID- 25133941 TI - Oxygen Cost of Recreational Horse-Riding in Females. AB - BACKGROUND: The purpose of this study was to characterize the physiological demands of a riding session comprising different types of recreational horse riding in females. METHODS: Sixteen female recreational riders (aged 17 to 54 years) completed an incremental cycle ergometer exercise test to determine peak oxygen consumption (VO2peak) and a 45-minute riding session based upon a British Horse Society Stage 2 riding lesson (including walking, trotting, cantering and work without stirrups). Oxygen consumption (VO2), from which metabolic equivalent (MET) and energy expenditure values were derived, was measured throughout. RESULTS: The mean VO2 requirement for trotting/cantering (18.4 +/- 5.1 ml.kg 1.min-1; 52 +/- 12% VO2peak; 5.3 +/- 1.1 METs) was similar to walking/trotting (17.4 +/- 5.1 ml.kg-1.min-1; 48 +/- 13% VO2peak; 5.0 +/- 1.5 METs) and significantly higher than for work without stirrups (14.2 +/- 2.9 ml.kg-1.min-1; 41 +/- 12% VO2peak; 4.2 +/- 0.8 METs) (P = .001). CONCLUSIONS: The oxygen cost of different activities typically performed in a recreational horse riding session meets the criteria for moderate intensity exercise (3-6 METs) in females, and trotting combined with cantering imposes the highest metabolic demand. Regular riding could contribute to the achievement of the public health recommendations for physical activity in this population. PMID- 25133942 TI - From the editor. Benefits of physical activity in the later years. PMID- 25133943 TI - The relationship between physical activity and perceived health status in older women: findings from the Woman's College Alumni Study. AB - Using data collected from the Woman's College (WC) Alumni Study, the purpose of this study was to determine whether perceived health status is related to physical activity in older women. A multiple linear regression analysis was conducted to examine the relationship between amounts of physical activity and self-reported health status. The results of the current study reveal that the level of physical activity is significantly correlated with perceived health status. The findings of this study have implications for the assessment of older individuals' health and may lead to interventions that are tailored to increase physical activity among older women. PMID- 25133944 TI - Physical and mental health correlates of self-efficacy in dementia family caregivers. AB - This study examined whether self-efficacy for controlling upsetting caregiving thoughts would longitudinally predict mental and physical health as well as utilization of psychotropic medications in help-seeking dementia family caregivers (N = 53). Positive associations were found between self-efficacy and self-reported mental health and physical health subscales of the Short Form Health Questionnaire-12, and negative correlations were found between self efficacy for controlling upsetting thoughts about caregiving and the number of psychotropic medications being utilized both cross-sectionally and longitudinally. These results suggest that self-efficacy for controlling upsetting thoughts may be a fruitful target area for further intervention research with dementia family caregivers. PMID- 25133945 TI - Generational juggling acts in midlife families: gendered and ethnocultural intersections. AB - This study draws upon a sociocultural stress and coping perspective to examine generational demands in midlife families. It examines both the predictors and family-related circumstances that contribute to perceptions of greater demand, with a focus on gendered and ethnocultural dimensions. Using mixed-methods, data are based on a sample of 236 parents collected in 2006/2007 from four cultural groups: British-, Chinese-, Southern European-, and South Asian Canadian. Key findings reveal that caregiving experiences remain highly gendered and are mediated by ethnocultural background and other work/family contextual characteristics. Recommendations for those who work directly with culturally diverse "sandwiched" generation families are highlighted. PMID- 25133946 TI - Attitudes and stereotypes regarding older women and HIV risk. AB - Persons aged 50 years and over will soon disproportionately represent the future of the HIV/AIDS epidemic. It is estimated that by 2015 older adults will represent 50% of persons living with HIV in the United States. Despite the HIV/AIDS growing population among older adults, attitudes, beliefs, and stereotypes toward older adults that exist in general society have affected HIV prevention, education, and care. Specifically, ageist attitudes about the sexuality of older adults in general and older women in particular, low clinical HIV suspicion among healthcare providers, lack of knowledge about risk among older women, and differentials in power related to negotiating sexual practices all lead to heightened concerns for the prevention, identification, and treatment of HIV disease in mature women. This article examines common attitudes, beliefs, and stereotypes that exist within general society as well as health and social service providers that place older women at a disadvantage when it comes to HIV prevention, education, and treatment. PMID- 25133950 TI - Acquired cutis laxa associated with heavy chain deposition disease involving dermal elastic fibers. AB - IMPORTANCE: Acquired cutis laxa is a rare cutaneous manifestation of hematologic malignancy. We report a case of gamma heavy chain deposition disease (HCDD) associated with acquired cutis laxa, renal involvement, and hypocomplementemia and propose a mechanism of elastic fiber degradation in the skin of this patient with HCDD. OBSERVATIONS: To determine the localization of immunoglobulin heavy chains and complement activation in the skin of a patient with HCDD, we examined her skin biopsy specimens under light and electron microscopy. Analysis demonstrated the deposition of gamma heavy chain and complement components C1q and C3 on the surfaces of dermal elastic fibers, indicating complement fixation by the deposited heavy chains. Electron microscopy revealed finely granular electron-dense deposits coating the surfaces of frayed dermal elastic fibers. CONCLUSIONS AND RELEVANCE: The pathogenesis of cutis laxa in this condition is poorly understood. We hypothesize a mechanism of elastic tissue destruction by complement fixation with resultant activation of the complement cascade ultimately causing elastolysis. Based on our findings and those of other reports, we propose that skin heavy chain deposition can serve as a marker of plasma cell secretory activity in HCDD, although further studies are needed. PMID- 25133951 TI - Regioselective formal hydroamination of styrenes with 1-phenyl-1H-tetrazole-5 thiol. AB - 1-Phenyl-1H-tetrazole-5-thiol 1 (PT-thiol) is employed in a unique Markovnikov selective formal hydroamination of styrenyl compounds in the presence of catalytic amounts of Ga(OTf)3. This gives rise to the formation of tetrazolothione moieties in an atom-economical manner. Mechanistically, we have determined that this transformation may occur by kinetically favored hydrothiolation, followed by rearrangement to the observed hydroamination products. PMID- 25133953 TI - Microthermodynamic interpretation of fluid states from FTIR measurements in lipid membranes: a Monte Carlo study. AB - Fourier transform infrared spectroscopy (FTIR) is usually employed to obtain transition temperatures of lipids and lipid mixtures and the effect on it of several effectors, such as cholesterol. However, no interpretation of the molecular information provided by the frequency shift to higher values observed at Tc is available. In this article, we demonstrate that data obtained by means of FTIR measurements contain information about the microscopic thermodynamics of the lipid-phase transition. By means of Monte Carlo simulation, we have been able to show that the frequency shift from low to high values can be taken as a two state transition of molecular constituents in a lattice rearrangement. According to the model, at temperatures below Tc all of the groups are defined in the lowest-energy state defined by the lowest frequency value and therefore they are all connected in a gel lattice. Above Tc, some groups may reach different energy states depending on the restrictions imposed on the groups. Ideally, when all of the groups are able to reach the highest frequency, a fully "fluid" state is reached, which is a disordered state. If we take this hypothetical state as a reference, it is possible to show that the higher states become less accessible. The model is suitable for describing the effect of cholesterol, which is able to dump the phase transition and is congruent with previous data denoting that in the so-called fluid phase the first four to five methylene groups remain in the gel state even above Tc. The frequency value attained above Tc depends on the nature of the lipid acyl chain. PMID- 25133954 TI - Polysaccharide-based networks from homogeneous chitosan-tripolyphosphate hydrogels: synthesis and characterization. AB - Polysaccharide networks, in the form of hydrogels and dried membranes based on chitosan and on the cross-linker tripolyphosphate (TPP), were developed using a novel approach. TPP was incorporated into chitosan by slow diffusion to favor a controlled gelation. By varying chitosan, TPP, and NaCl concentration, transition from inhomogeneous to homogeneous systems was achieved. Rheology and uniaxial compression tests enabled to identify the best performing hydrogel composition with respect to mechanical properties. FTIR, (31)P NMR, and spectrophotometric methods were used to investigate the interaction chitosan-TPP, the kinetics of phosphates diffusion during the dialysis and the amount of TPP in the hydrogel. A freeze-drying procedure enabled the preparation of soft pliable membranes. The lactate dehydrogenase assay demonstrated the biocompatibility of the membranes toward fibroblasts. Overall, we devised a novel approach to prepare homogeneous macroscopic chitosan/TPP-based biomaterials with tunable mechanical properties and good biocompatibility that show good potential as novel polysaccharide derivatives. PMID- 25133955 TI - Dynamic observation of phase transformation behaviors in indium(III) selenide nanowire based phase change memory. AB - Phase change random access memory (PCRAM) has been extensively investigated for its potential applications in next-generation nonvolatile memory. In this study, indium(III) selenide (In2Se3) was selected due to its high resistivity ratio and lower programming current. Au/In2Se3-nanowire/Au phase change memory devices were fabricated and measured systematically in an in situ transmission electron microscope to perform a RESET/SET process under pulsed and dc voltage swept mode, respectively. During the switching, we observed the dynamic evolution of the phase transformation process. The switching behavior resulted from crystalline/amorphous change and revealed that a long pulse width would induce the amorphous or polycrystalline state by different pulse amplitudes, supporting the improvement of the writing speed, retention, and endurance of PCRAM. PMID- 25133956 TI - Work zone safety analysis and modeling: a state-of-the-art review. AB - OBJECTIVE: Work zone safety is one of the top priorities for transportation agencies. In recent years, a considerable volume of research has sought to determine work zone crash characteristics and causal factors. Unlike other non work zone-related safety studies (on both crash frequency and severity), there has not yet been a comprehensive review and assessment of methodological approaches for work zone safety. To address this deficit, this article aims to provide a comprehensive review of the existing extensive research efforts focused on work zone crash-related analysis and modeling, in the hopes of providing researchers and practitioners with a complete overview. METHODS: Relevant literature published in the last 5 decades was retrieved from the National Work Zone Crash Information Clearinghouse and the Transport Research International Documentation database and other public digital libraries and search engines. Both peer-reviewed publications and research reports were obtained. Each study was carefully reviewed, and those that focused on either work zone crash data analysis or work zone safety modeling were identified. The most relevant studies are specifically examined and discussed in the article. RESULTS: The identified studies were carefully synthesized to understand the state of knowledge on work zone safety. Agreement and inconsistency regarding the characteristics of the work zone crashes discussed in the descriptive studies were summarized. Progress and issues about the current practices on work zone crash frequency and severity modeling are also explored and discussed. The challenges facing work zone safety research are then presented. CONCLUSIONS: The synthesis of the literature suggests that the presence of a work zone is likely to increase the crash rate. Crashes are not uniformly distributed within work zones and rear-end crashes are the most prevalent type of crashes in work zones. There was no across-the-board agreement among numerous papers reviewed on the relationship between work zone crashes and other factors such as time, weather, victim severity, traffic control devices, and facility types. Moreover, both work zone crash frequency and severity models still rely on relatively simple modeling techniques and approaches. In addition, work zone data limitations have caused a number of challenges in analyzing and modeling work zone safety. Additional efforts on data collection, developing a systematic data analysis framework, and using more advanced modeling approaches are suggested as future research tasks. PMID- 25133957 TI - The cyanide ligands of [FeFe] hydrogenase: pulse EPR studies of (13)C and (15)N labeled H-cluster. AB - The two cyanide ligands in the assembled cluster of [FeFe] hydrogenase originate from exogenous l-tyrosine. Using selectively labeled tyrosine substrates, the cyanides were isotopically labeled via a recently developed in vitro maturation procedure allowing advanced electron paramagnetic resonance techniques to probe the electronic structure of the catalytic core of the enzyme. The ratio of the isotropic (13)C hyperfine interactions for the two CN(-) ligands-a reporter of spin density on their respective coordinating iron ions-collapses from ~5.8 for the Hox form of hydrogenase to <2 for the CO-inhibited form. Additionally, when the maturation was carried out using [(15)N]-tyrosine, no features previously ascribed to the nitrogen of the bridging dithiolate ligand were observed suggesting that this bridge is not sourced from tyrosine. PMID- 25133959 TI - Probing local strain at MX(2)-metal boundaries with surface plasmon-enhanced Raman scattering. AB - Interactions between metal and atomically thin two-dimensional (2D) materials can exhibit interesting physical behaviors that are of both fundamental interests and technological importance. In addition to forming a metal-semiconductor Schottky junction that is critical for electrical transport, metal deposited on 2D layered materials can also generate a local mechanical strain. We investigate the local strain at the boundaries between metal (Ag, Au) nanoparticles and MX2 (M = Mo, W; X = S) layers by exploiting the strong local field enhancement at the boundary in surface plasmon-enhanced Raman scattering (SERS). We show that the local mechanical strain splits both the in-plane vibration mode E2g(1) and the out-of plane vibration mode A1g in monolayer MoS2, and activates the in-plane mode E1g that is normally forbidden in backscattering Raman process. In comparison, the effects of mechanical strain in thicker MoS2 layers are significantly weaker. We also observe that photoluminescence from the indirect bandgap transition (when the number of layers is >=2) is quenched with the metal deposition, while a softened and broadened shoulder peak emerges close to the original direct-bandgap transition because of the mechanical strain. The strain at metal-MX2 boundaries, which locally modifies the electronic and phonon structures of MX2, can have important effects on electrical transport through the metal-MX2 contact. PMID- 25133960 TI - A new library of arsine, stibine-stabilized N-heterocyclic carbene palladium complexes: synthesis, structures and activities in C-C and C-N coupling reactions. AB - A series of new N-heterocyclic carbene palladium complexes bearing AsPh3 and SbPh3 functions PdCl2(IMes)(AsPh3) (1a), PdCl2(IMes)(SbPh3) (1b), PdCl2(IPr)(AsPh3) (1c), PdCl2(IPr)(SbPh3) (1d), PdCl2(SIMes)(AsPh3) (2a), PdCl2(SIMes)(SbPh3) (2b), PdCl2(SIPr)(AsPh3) (2c), and PdCl2(SIPr)(SbPh3) (2d) (IMes = N,N'-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene; IPr = N,N'-bis-(2,6 di(iso-propyl)phenyl)imidazol-2-ylidene; SIMes = N,N'-bis-(2,4,6 trimethylphenyl)imidazolidin-2-ylidene; SIPr = N,N'-bis-(2,6-di(iso propyl)phenyl)imidazolidin-2-ylidene) was synthesized and fully characterized by (1)H NMR, (13)C NMR, and FT-IR spectroscopy, elemental analysis and single crystal X-ray crystallography. The catalytic potential of these arsine and stibine-stabilized carbene palladium complexes for Pd-mediated transformations was investigated with various substrates in the Hiyama cross-coupling reactions and Buchwald-Hartwig aminations. The results demonstrate that these complexes show high catalytic activity and good tolerance to various chemical functions. PMID- 25133958 TI - Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia. AB - IMPORTANCE: Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. OBJECTIVE: To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTS: We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. MAIN OUTCOMES AND MEASURES: Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. RESULTS: We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND RELEVANCE: This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia. PMID- 25133961 TI - Resource utilization and use of life-extending therapies and corticosteroids in prostate cancer patients with corticosteroid-sensitive comorbidities. AB - OBJECTIVES: Corticosteroids (CSs) are used concomitantly with life-extending therapies (LETs) in patients with castration-resistant prostate cancer (CRPC). This study examined time to LETs, LETs and concomitant CS adherence, and monthly all-cause healthcare utilization and costs in patients with CPRC with and without CS-sensitive comorbidities in the Veterans Health Administration population. METHODS: Patients had CRPC if records showed prostate cancer diagnosis, medical/surgical castration and >=2 prostate-specific antigen increases through 1 June 2007-31 May 2012. CS-sensitive comorbidities were assessed 6 months prior to the index date. Adherence, defined as medication possession ratio (MPR) >=0.8, among patients initiating LETs (cabazitaxel, docetaxel, or abiraterone acetate) before 30 November 2011, resource utilization and costs among patients with concomitant CS were assessed. Statistical analysis included descriptive, Cox proportional hazards, and logistic regression models. RESULTS: Common CS sensitive conditions among 12,128 patients with CRPC included hypertension (75.74%) and hyperlipidemia (54.69%). Those with glaucoma (hazard ratio [HR] = 0.67), ischemic heart disease (HR = 0.78), and peripheral vascular disease (PVD) (HR = 0.78) were less likely to be prescribed LETs (all p < 0.01). Duration of LET was shorter among patients with CS-sensitive comorbidities (125.02 vs 133.08 days; p = 0.04) in the 6 month follow-up period. Among LET-treated patients with and without CS-sensitive comorbidities, less than half had MPR >= 0.8 (LET: 48.72% vs 54.05%; concomitant CS: 42.19% vs 40.54%, respectively). Cerebrovascular disease (odds ratio = 0.107; 95% confidence interval = 0.012 to 0.966) and PVD (odds ratio = 0.523; 95% confidence interval = 0.276 to 0.991) were associated with reduced CS adherence. Among patients with concomitant CS, those with CS-sensitive comorbidities had more inpatient stays than those without (20.45% vs 12.88%; p = 0.033), incurring higher monthly inpatient costs ($1157 vs $342; p < 0.0001) and total costs ($5725 vs $4772; p = 0.036). CONCLUSION: CS sensitive conditions influence initiation and duration of LETs, concomitant CS adherence, inpatient stays, and total costs. Future efforts should focus on specific strategies for treating prostate cancer patients with CS-sensitive comorbidities to ensure that they have appropriate access to LETs and to reduce costs and inpatient stays. Study limitations include the use of retrospective claims data and the relatively restricted subpopulation of older North American males. PMID- 25133962 TI - Acute postoperative pain relief with immediate-release tapentadol: randomized, double-blind, placebo-controlled study conducted in South Korea. AB - OBJECTIVE: To broaden the ethnic groups in which tapentadol IR is evaluated for treating acute postoperative pain to include Asians. METHODS: In this phase 3, multicenter, double-blind, randomized study, 352 Korean adults with moderate-to severe pain following hallux valgus surgery received tapentadol IR 50 or 75 mg or placebo orally every 4-6 hours for 72 hours. Patients requesting other (rescue) analgesics during this period were discontinued for lack of efficacy. The primary endpoint, sum of pain intensity difference (SPID) over 48 hours, was evaluated based on the difference between tapentadol IR and placebo in least squares (LS) mean change from baseline using analysis of covariance (ANCOVA). Secondary endpoints included the time to first rescue medication use and the distribution of responder rates. RESULTS: A treatment effect, favoring tapentadol IR, was observed for SPID48 (p < 0.001 for both doses vs. placebo, ANCOVA). The between group difference (vs. placebo) in LS means of SPID48 was 76.4 (95% CI: 51.0, 101.7) for tapentadol IR 50 mg and 90.6 (95% CI: 65.1, 116.1) for tapentadol IR 75 mg. Time to first rescue medication use was delayed for tapentadol IR (p < 0.001 for both doses vs. placebo; log-rank test). The distribution of responders at 12, 24, 48, and 72 hours favored tapentadol IR (p <= 0.001 for both doses vs. placebo; Cochran-Mantel-Haenszel test). Dizziness, nausea, and vomiting were each reported in >= 10% tapentadol-treated patients and at an incidence >= 2-fold higher vs. placebo. The study findings may be limited by study drug dosing every 4 to 6 hours and frequent monitoring during treatment, neither of which mimic pain treatment in clinical practice. However, any potential bias based on this systematic monitoring of patients would be mitigated by the randomized, double blind nature of the study, with all treatment groups similarly affected by such biases, if any. CONCLUSIONS: Tapentadol IR reduced acute pain intensity, significantly more than placebo, after orthopedic surgery in Korean patients. CLINICAL TRIAL REGISTRATION: NCT01516008. PMID- 25133964 TI - The latest on optical coherence tomography. PMID- 25133963 TI - Etoricoxib in the treatment of Korean patients with osteoarthritis in a double blind, randomized controlled trial. AB - OBJECTIVE: We evaluated the COX-2 inhibitors, etoricoxib and celecoxib, in Korean patients with osteoarthritis (OA). METHODS: This study included patients (>= 40 years of age) with a clinical and radiographic diagnosis of knee OA. Patients were randomized to etoricoxib 30 mg (qd) or celecoxib 200 mg (qd) in a 12 week randomized, controlled, double-blind study. Prior NSAID users were to demonstrate a worsening of symptoms upon withdrawal of medication. Efficacy endpoints included the time-weighted average change from baseline in the WOMAC VA 3.0 Pain Subscale (100 mm Visual Analog Scale [VAS]; primary endpoint), the WOMAC VA 3.0 Physical Function Subscale (100 mm VAS), and Patient Global Assessment of Disease Status (PGAD) (100 mm VAS). The primary hypothesis was that etoricoxib 30 mg is non-inferior to celecoxib 200 mg as assessed by the primary endpoint (the non inferiority margin was set at 10 mm VAS). Adverse events (AEs), laboratory parameters, and vital signs were monitored. RESULTS: There were 239 patients (89.5% female; mean age: 63.3 years) randomized to etoricoxib 30 mg (n = 120) and celecoxib 200 mg (n = 119). The differences (etoricoxib vs celecoxib) in least square (LS) mean change (95% CI) for WOMAC Pain, WOMAC Physical Function, and PGAD were -1.63 mm (-5.37, 2.10), -1.32 mm (-4.88, 2.23), and -1.09 mm (-5.48, 3.30), respectively. Drug-related clinical AEs occurred in 6.7% (etoricoxib) and 2.5% (celecoxib) of patients. This study was limited because it was not designed or powered to adequately capture and evaluate rare AEs associated with NSAID treatment. CONCLUSIONS: Etoricoxib 30 mg administered once daily in Korean patients with knee OA demonstrated non-inferior clinical efficacy to celecoxib 200 mg over 12 weeks of treatment as assessed by all primary and secondary outcomes. Etoricoxib 30 mg qd and celecoxib 200 mg qd were generally safe and well tolerated. CLINICAL TRIAL REGISTRATION: NCT01554163. PMID- 25133965 TI - Optical coherence tomography in papilledema: what am I missing? AB - BACKGROUND: Grading of papilledema severity is subjective and based on monocular fundus features of the optic nerve. Interobserver agreement on grading the severity of papilledema is poor among expert observers, even using well-defined criteria such as the Frisen scale, which is a non-continuous ordinal scale of grading. Furthermore, non-expert clinicians often find it difficult to properly view and interpret features of the optic nerve using ophthalmoscopy, which can lead to failure to diagnose papilledema in non-ophthalmologic care settings. This may delay treatment, which can result in vision loss. Distinguishing papilledema from pseudopapilledema can also be difficult when surface drusen are not easily identified. Once papilledema is diagnosed, it is often difficult to determine whether a reduction in optic nerve edema is due solely to improvement in the status of the nerve or whether this represents concomitant loss of axons and viable retinal ganglion cells, leading to a poor visual outcome. Timely advancement of treatment would occur if loss of neurons could be diagnosed at an earlier stage of evaluation while optic disc edema is still present. This review will critically assess the role of optical coherence tomography (OCT) in solving these problems by providing an advanced imaging approach for diagnosis of papilledema and evaluating its severity on a continuous scale and evaluating the causes of visual loss in the setting of a swollen nerve. METHODS ACQUISITION: The published literature (PubMed) was reviewed from 2000 to 2014 on the use of OCT for diagnosing papilledema, differentiating it from pseudopapilledema, providing a continuous scale of its severity and in evaluating causes of visual loss. RESULTS: Recent evidence shows that OCT analysis of the retinal nerve fiber layer and retinal ganglion cell layer in papilledema can be associated with misleading artifacts due to layer segmentation failures. Newer 3D algorithms using neighboring locations help to overcome these problems. Disc volume appears to be a promising continuous measure of papilledema that is robust and has less associated artifacts. Buried optic disc drusen can be identified using enhanced depth OCT imaging, but recent studies have shown poor ability to differentiate papilledema from pseudopapilledema using OCT when the degree of disc evaluation is similar. Analysis of the retinal ganglion cell layer shows promise of early detection of vision loss due to neuronal injury. Subretinal fluid is easily identified with OCT and can help to identify a potentially reversible component of vision loss. Newer OCT imaging methods will allow the definition of capillaries and flow within them in and around the optic nerve head. CONCLUSIONS: Currently, the most useful OCT derived features relevant to papilledema are disc volume, subretinal fluid, buried disc drusen, and thickness of the retinal ganglion cell layer. PMID- 25133966 TI - Clinical trials to clinical use: using vision as a model for multiple sclerosis and beyond. AB - Optical coherence tomography (OCT) has made possible the structure-function correlations that uniquely characterize the afferent visual pathway as a model for understanding multiple sclerosis (MS) and for developing new treatments. During the past decade, OCT measures of retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCL + IPL) thickness have evolved from being a means to validate visual function tests, such as low-contrast letter acuity, to provide a window on the axonal and neuronal loss that are now widely recognized as contributors to permanent visual dysfunction in MS. Although acute optic neuritis (ON) leads to thinning of the RNFL by 20%-40% within 3 months after a single episode, thinning of the RNFL and GCL + IPL occur over time in MS eyes even in the absence of an acute ON history. As such, OCT and its functional and patient-reported correlates of low-contrast acuity and vision-specific quality of life (QOL) have now been incorporated into MS clinical trials. Results of an ongoing, phase 2 trial of a remyelinating agent that uses acute ON as a model for assessing therapeutic efficacy will define even further the important role for OCT in documenting structural changes as we move forward from clinical trials to clinical use. PMID- 25133967 TI - Retinal segmentation using multicolor laser imaging. AB - Spectral-domain optical coherence tomography (SD-OCT) changed 3 worlds: clinical care, clinical research, and the regulatory environment of phases 2, 3, and 4 pharmaceutical and surgical trials. OCT is now undergoing another transformation with multicolor technology, which acquires images using data from 3 simultaneous lasers: red, green, and blue, taking advantage of the different wavelengths of each of these colors to most precisely image 3 different zones of the retina. Rather than seeing only the surface of the retina and optic disc and any large lesions in the deeper retina, this technology provides a topographic map of the outer (red), mid (green), and inner (blue) retina somewhat similar to what is observed with fundus autoflourescence of deep retina, retinal pigment epithelium, and choroid. Multicolor imaging will supplement and help to define what is observed with traditional fundus photography and SD-OCT. In addition, it may demonstrate abnormalities when routine photography is normal and when SD-OCT findings are equivocal. This review will illustrate the basic principles of multicolor imaging and will show clinical examples of how this technique can further define retinal and optic nerve pathology. PMID- 25133968 TI - Optical coherence tomography technologies: which machine do you want to own? AB - Optical coherence tomography (OCT) has evolved over the past decade to become one of the most important ancillary tests in ophthalmic practice. This noninvasive ocular imaging technique provides high-resolution, cross-sectional images of the retinal nerve fiber layer (RNFL), macular region, ganglion cell layer, and optic nerve head. With OCT, we can learn much about axonal-neuronal integrity in the anterior aspect of the afferent visual pathway and gain insights about mechanisms of brain injury in various central nervous system disorders. PMID- 25133969 TI - Liver agenesis with omphalocele: a report of two human embryos using serial histological sections. AB - We identified 2 human embryos, with crown-rump lengths (CRLs) of 22 mm and 23 mm and a gestational age of approximately 7 weeks (O'Rahilly's stage 21-22), with liver agenesis and omphalocele. Serial histological sections were prepared of the entire body of one specimen, whereas sections of the neck, including the upper part of the heart, were missed for the other specimen as a result of tissue damage during the abortion. In addition, isolated omphalocele was assessed in another embryo (CRL = 25 mm) for comparison with atypical omphalocele in the embryos with liver agenesis. The 2 embryos with liver agenesis were characterized by (1) the absence of the anterior part of the diaphragm; (2) abnormality in the venous pole of the heart; (3) a normal stomach in the left upper abdominal cavity; and (4) normal pancreas development with normal midgut rotation. The most likely cause of liver agenesis, when combined with isolated omphalocele, was a defect in the anterior extension or migration of the septum transversum rather than a mechanical separation of the hepatic diverticulum from the septum transversum. PMID- 25133971 TI - Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for enhanced cancer cell apoptosis. AB - Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core-shell nanoparticle (MCNP) mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis. PMID- 25133972 TI - Silymarin inhibits the progression of fibrosis in the early stages of liver injury in CCl4-treated rats. AB - Liver fibrosis, a common condition occurring during the evolution of almost all chronic liver diseases, is the consequence of hepatocyte injury that leads to the activation of Kupffer cells and hepatic stellate cells (HSC). Silymarin (Si) is a herbal product widely used for its hepatoprotective potential. Our study aims to investigate the effects of two different doses of Silymarin on a CCl4-induced model of liver fibrosis with a focus on the early stages of liver injury. Fifty Wistar rats were randomly divided into five groups (n=10): control group (sunflower oil twice a week); CMC group (carboxymethyl cellulose five times a week, sunflower oil twice a week); CCl4 group (CCl4 in sunflower oil, by gavage, twice a week); CCl4+Si 50 group (CCl4 twice a week, Silymarin 50 mg/b.w. in CMC five times a week); and CCl4+Si 200 group (similar to the previous group, with Si 200 mg/b.w.). One month after the experiment began we explored hepato-cytolysis (aminotransferases and lactate dehydrogenase), oxidative stress, fibrosis (histological score, hyaluronic acid), markers of HSC activation (transforming growth factor beta1 [TGF-beta1], and alpha-smooth muscle actin [alpha-SMA] expression by western blot) and activation of Kupffer cells by immunohistochemistry. Our data showed that Si 50 mg/b.w. had the capacity of reducing oxidative stress, hepato-cytolysis, fibrosis, activation of Kupffer cells, and the expression of alpha-SMA and TGF-beta1 with better results than Si 200 mg/b.w. Thus, the usual therapeutic dose of Silymarin, administered in the early stages of fibrotic changes is capable of inhibiting the fibrogenetic mechanism and the progression of initial liver fibrosis. PMID- 25133975 TI - A highly enantioselective hydrogenation of silyl enol ethers catalyzed by chiral frustrated Lewis pairs. AB - Using a simple combination of tri-tert-butylphosphine and chiral borane generated in situ by the hydroboration of chiral diene with HB(C6F5)2 as a frustrated Lewis pair catalyst, a highly enantioselective metal-free hydrogenation of silyl enol ethers was successfully realized to furnish a variety of optically active secondary alcohols in 93-99% yields with 88->99% ee's. PMID- 25133976 TI - Elucidating the ring inversion mechanism(s) for biscalixarenes. AB - Biscalix[4]arene can be constructed from a calix[4]arene by substitution of a methylene bridge hydrogen by another equivalent moiety. The use of biscalix[4]arenes (biscal) as precursors for the creation of new polymetallic clusters such as single-molecule magnets has potential in the fields of data storage and other applications. Polymetallic clusters involving biscal are expected to preferentially involve octadentate binding to two metal centers (one metal center per tetraphenolic pocket), requiring full inversion of one of the annular rings. In this work, we use density functional theory to establish the mechanism behind this process, considering the various energy pathways and providing insight into the preferred route to full and partial inversion. Fourteen possible pathways to full inversion are presented, including all transition states (up to seven per pathway). Subsequently, the lowest energy pathway to full inversion was found to have a barrier height of 19.31 kcal mol( 1). Solvent optimizations using PCM (with and without SMD) and CPCM solvent models suggest long-range solvent effects may be relatively unimportant in the inversion process. This study represents the first use of density functional theory to elucidate the entire potential energy surface, including barrier heights, of the ring inversion process of biscalix[4]arenes. PMID- 25133974 TI - Spectacle correction versus no spectacles for prevention of strabismus in hyperopic children. AB - BACKGROUND: Hyperopia (far-sightedness) in infancy requires accommodative effort to bring images into focus. Prolonged accommodative effort has been associated with an increased risk of strabismus (eye misalignment). Strabismus makes it difficult for the eyes to work together and may result in symptoms of asthenopia (eye strain) and intermittent diplopia (double vision), and makes near work tasks difficult to complete. Untreated strabismus may result in the development of amblyopia (lazy eye). The prescription of spectacles to correct hyperopic refractive error is believed to prevent the development of strabismus. OBJECTIVES: To assess the effectiveness of prescription spectacles compared with no intervention for the prevention of strabismus in infants and children with hyperopia. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 4), Ovid MEDLINE, Ovid MEDLINE In Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to April 2014), EMBASE (January 1980 to April 2014), PubMed (1966 to April 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 April 2014. We also searched the Science Citation Index database in September 2013. SELECTION CRITERIA: We included randomized controlled trials and quasi-randomized trials investigating the assignment to spectacle intervention or no treatment for children with hyperopia. The definition of hyperopia remains subjective, but we required it to be at least greater than +2.00 diopters (D) of hyperopia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using the standard methodologic procedures expected by The Cochrane Collaboration. One review author entered data into Review Manager and a second review author verified the data entered. The two review authors resolved discrepancies at all stages of the review process. MAIN RESULTS: We identified three randomized controlled trials (855 children enrolled) in this review. These trials were all conducted in the UK with follow-up periods ranging from one to 3.5 years. We judged the included studies to be at high risk of bias, due to use of quasi-random methods for assigning children to treatment, no masking of outcomes assessors, and high proportions of drop-outs. None of the three trials accounted for missing data and analyses were limited to the available-case data (674 (79%) of 855 children enrolled for the primary outcome). These factors impair our ability to assess the effectiveness of treatment.Analyses incorporating the three trials we identified in this review (674 children) suggested the effect of spectacle correction initiated prior to the age of one year in hyperopic children between three and four years of age is uncertain with respect to preventing strabismus (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.44 to 1.15; very low quality evidence). Based on a meta-analysis of three trials (664 children), the risk of having visual acuity worse than 20/30 at three years of age was also uncertain for children with spectacles compared with those without spectacle correction irrespective of compliance (RR 0.87; 95% CI 0.60 to 1.26; very low quality evidence).Emmetropization was reported in two trials: one trial suggested that spectacles impede emmetropization, and the second trial reported no difference in the rate of refractive error change. AUTHORS' CONCLUSIONS: Although children who were allocated to the spectacle group were less likely to develop strabismus and less likely to have visual acuity worse than 20/30 children allocated to no spectacles, these effects may have been chance findings, or due to bias. Due to the high risk of bias and poor reporting of included trials, the true effect of spectacle correction for hyperopia on strabismus is still uncertain. PMID- 25133977 TI - Reward dependence moderates smoking-cue- and stress-induced cigarette cravings. AB - BACKGROUND: Cigarette cravings following exposure to smoking cues in a smoker's environment are thought to play an important role in cessation failure. The possibility that dispositional factors may impact cue-induced cravings, though intriguing, has received little attention. According to Cloninger's Tridimensional Personality Theory, factors such as reward dependence (RD), harm avoidance (HA), and novelty seeking (NS) may figure prominently in risk for addiction, as well as relapse, in individuals attempting to abstain from drug and alcohol use. Particularly interesting in this regard is the possibility that smokers with higher levels of RD, who are especially sensitive to reward signals, will have heightened craving reactions to smoking cues. METHODS: To that end, non treatment-seeking nicotine dependent smokers (n=96, mean age=41.1, 47% African American, 17% Caucasian, 22% Hispanic, 19.3cigs/day, FTND=7.5) underwent a classic experimental cue-induction, during which they were exposed to imagery of: (1) smoking, (2) neutral, and (3) stress cues, and reported their cigarette cravings (0-100) before and after each exposure. Participants also completed the Tridimensional Personality Questionnaire. RESULTS: Not surprisingly, smoking and stress cues (but not neutral cues) elicited significant elevations in craving (p's<0.0001). Consistent with study hypothesis, smokers who scored higher on RD had stronger craving reactions to both smoking cues (p<.02) and stress cues (p<.03). CONCLUSIONS: Findings raise the possibility that dispositional characteristics, in particular, reward dependence, influence smoking by potentiating reactions to environmental smoking cues. Furthermore, the similar effects of RD on stress-induced craving suggest that both cue-and stress-induced cravings may be influenced by a common underlying disposition. PMID- 25133978 TI - The relationship between perceived stress and cue sensitivity for alcohol. AB - Previous research has shown that cue sensitivity and stress affect the risk for relapse in alcohol-dependent patients. Theoretically, a link between the two can be expected. However, a clear overview of the interplay of these factors is not yet available. The purpose of this review was to examine the empirical evidence for the influence of stress on sensitivity for alcohol-related cues. Empirical studies indexed in PubMed, EMBASE, PsycINFO, and Web of Knowledge that assessed the relation between stress and sensitivity for alcohol-related cues using subjective, behavioral and/or physiological measures were included in the review. Of the 359 articles screened, 12 were included in the review. Nine articles supported the existence of the relationship between stress and heightened cue sensitivity for alcohol-related cues, whereas three articles did not support our hypothesis. We conclude that the relationship between stress and sensitivity to alcohol cues appears to exist. In fact, there may be different factors at play: our review points toward (1) differences between the effect of psychological stress and physiological stress on cue-sensitivity, and (2) individual differences regarding coping drinking which may explain stress-induced cues sensitivity. PMID- 25133979 TI - Magnetic relaxations arising from spin-phonon interactions in the nonthermally activated temperature range for a double-decker terbium phthalocyanine single molecule magnet. AB - Magnetic relaxations arising from spin-phonon interactions for a magnetically diluted double-decker terbium phthalocyanine single molecule magnet, dil1, in the nonthermally activated temperature range have been investigated. While the relaxation time, tau, is independent of the external static magnetic field, H(dc), in the high temperature range, where linear relationships between -ln tau and T(-1) are observed in the Arrhenius plot, magnetic field dependences for tau are observed in the lower temperature range. The tau(-1) vs H(dc) plot at 12 K fits the quadric curve when H(dc) < 12 kOe, while linear relationships are observed in the tau(-1) vs T plots in the temperature range of 12-20 K. These results indicate that the direct process is the dominant magnetic relaxation pathway in the nonthermally activated temperature range, while the contribution from the Raman process, if any, is not observable. We emphasize in this paper that the contribution from the thermal relaxation processes and the quantum tunneling of magnetizations (QTMs) to the experimentally observed magnetic relaxations must be evaluated carefully in order to avoid confusion between the thermal and quantum-mechanical relaxation pathways. PMID- 25133973 TI - Nuclear cytoplasmic trafficking of proteins is a major response of human fibroblasts to oxidative stress. AB - We have used a subcellular spatial razor approach based on LC-MS/MS-based proteomics with SILAC isotope labeling to determine changes in protein abundances in the nuclear and cytoplasmic compartments of human IMR90 fibroblasts subjected to mild oxidative stress. We show that response to mild tert-butyl hydrogen peroxide treatment includes redistribution between the nucleus and cytoplasm of numerous proteins not previously associated with oxidative stress. The 121 proteins with the most significant changes encompass proteins with known functions in a wide variety of subcellular locations and of cellular functional processes (transcription, signal transduction, autophagy, iron metabolism, TCA cycle, ATP synthesis) and are consistent with functional networks that are spatially dispersed across the cell. Both nuclear respiratory factor 2 and the proline regulatory axis appear to contribute to the cellular metabolic response. Proteins involved in iron metabolism or with iron/heme as a cofactor as well as mitochondrial proteins are prominent in the response. Evidence suggesting that nuclear import/export and vesicle-mediated protein transport contribute to the cellular response was obtained. We suggest that measurements of global changes in total cellular protein abundances need to be complemented with measurements of the dynamic subcellular spatial redistribution of proteins to obtain comprehensive pictures of cellular function. PMID- 25133980 TI - Advanced thermopower wave in novel ZnO nanostructures/fuel composite. AB - Thermopower wave is a new concept of energy conversion from chemical to thermal to electrical energy, produced from the chemical reaction in well-designed hybrid structures between nanomaterials and combustible fuels. The enhancement and optimization of energy generation is essential to make it useful for future applications. In this study, we demonstrate that simple solution-based synthesized zinc oxide (ZnO) nanostructures, such as nanorods and nanoparticles are capable of generating high output voltage from thermopower waves. In particular, an astonishing improvement in the output voltage (up to 3 V; average 2.3 V) was achieved in a ZnO nanorods-based composite film with a solid fuel (collodion, 5% nitrocellulose), which generated an exothermic chemical reaction. Detailed analyses of thermopower waves in ZnO nanorods- and cube-like nanoparticles-based hybrid composites have been reported in which nanostructures, output voltage profile, wave propagation velocities, and surface temperature have been characterized. The average combustion velocities for a ZnO nanorods/fuel and a ZnO cube-like nanoparticles/fuel composites were 40.3 and 30.0 mm/s, while the average output voltages for these composites were 2.3 and 1.73 V. The high output voltage was attributed to the amplified temperature in intermixed composite of ZnO nanostructures and fuel due to the confined diffusive heat transfer in nanostructures. Moreover, the extended interfacial areas between ZnO nanorods and fuel induced large amplification in the dynamic change of the chemical potential, and it resulted in the enhanced output voltage. The differences of reaction velocity and the output voltage between ZnO nanorods- and ZnO cube-like nanoparticles-based composites were attributed to variations in electron mobility and grain boundary, as well as thermal conductivities of ZnO nanorods and particles. Understanding this astonishing increase and the variation of the output voltage and reaction velocity, precise ZnO nanostructures, will help in formulating specific strategies for obtaining enhanced energy generation from thermopower waves. PMID- 25133981 TI - Effects of holmium laser enucleation of the prostate on sexual function. AB - OBJECTIVE: To evaluate the effects of holmium laser enucleation of the prostate (HoLEP) on sexual function. METHODS: A retrospective analysis of 202 sexually active patients who underwent HoLEP was performed. Patients were assessed at baseline and 3 and 12 months post-HoLEP. Evaluations included uroflowmetry and symptom questionnaires (five-item version of the International Index of Erectile Function [IIEF-5], ICIQ-male sexual matters associated with LUTS [ICIQ-MLUTSsex], American Urological Association symptom score [AUA-SS], and single-question quality of life [QoL] score). Nonparametric, Fisher's exact, and chi-squared tests were used to assess changes from baseline and to identify risk factors, if any, associated with deterioration of sexual function after surgery. RESULTS: No significant differences were found between the preoperative and postoperative scores on the questionnaires that evaluated erection quality. However, 6.9% and 12.4% of the patients reported an increase or a reduction, respectively, of greater than five points in total IIEF-5 score. The reduction in IIEF-5 score was statistically significant only in the subgroup of patients without preoperative erectile dysfunction (ED). No preoperative characteristics and no parameters related to the surgery or postoperative outcome were significantly associated with the impairment of erection quality after surgery. In fact, neither capsular perforation nor the total laser energy used during the procedure affected erections. Loss of antegrade ejaculation was found in 70.3% of patients, while 21% reported a reduction in semen quantity. However, concern regarding ED or ejaculatory dysfunctions decreased with surgery. CONCLUSIONS: Although erectile function was not altered in the vast majority of patients after HoLEP, patients without preoperative ED displayed a relatively small, but still significant, negative effect on erections. The overwhelming majority of patients suffered from retrograde ejaculation after surgery. PMID- 25133982 TI - Optimizing health for persons with multiple chronic conditions. PMID- 25133984 TI - Single Entry Communities Increase Trip Distance and May Overestimate Neighborhood Walkability. AB - BACKGROUND: Neighborhood walkability is being promoted as an important factor in public health efforts to decrease rates of physical inactivity. Single entry communities (SEC), communities with only 1 entrance/exit, may result in an over estimation of walkability. This design makes direct walking routes outside the community nearly impossible and results in increased trip distance. The purpose of this study was to determine if accounting for SECs resulted in a significant difference in street connectivity. METHODS: Twenty geographically different Las Vegas neighborhoods were chosen and the number of true intersections measured in ArcGIS. Neighborhoods were then assessed for the presence of SECs using google maps, ArcGIS land imagery, and field observation. Intersections inside SECs were removed. A paired t test was used to assess the mean difference of intersection density before and after adjustment. RESULTS: There was a statistically significant decrease in the number of true intersections after the adjustment (before mean = 57.8; after mean = 45.7). The eta squared statistic indicates a large effect size (0.3). CONCLUSIONS: Single entry communities result in an over estimation of street connectivity. If SECs are not accounted for, trip distances will be underestimated and public health efforts to promote walking through walkable neighborhoods may prove less effective. PMID- 25133983 TI - Concerted bioinformatic analysis of the genome-scale blood transcription factor compendium reveals new control mechanisms. AB - Transcription factors play a key role in the development of a disease. ChIP sequencing has become a preferred technique to investigate genome-wide binding patterns of transcription factors in vivo. Although this technology has led to many important discoveries, the rapidly increasing number of publicly available ChIP-sequencing datasets still remains a largely unexplored resource. Using a compendium of 144 publicly available murine ChIP-sequencing datasets in blood, we show that systematic bioinformatic analysis can unravel diverse aspects of transcription regulation; from genome-wide binding preferences, finding regulatory partners and assembling regulatory complexes, to identifying novel functions of transcription factors and investigating transcription dynamics during development. PMID- 25133985 TI - Identification of the halogenated compounds resulting from the 1997 Plastimet Inc. fire in Hamilton, Ontario, using comprehensive two-dimensional gas chromatography and (ultra)high resolution mass spectrometry. AB - Between July 9-12, 1997, at least 400 tonnes of polyvinyl chloride (PVC) were consumed in a fire at the Plastimet Inc. plastics recycling facility in Hamilton, Ontario, Canada. This led to the release of contaminants, including highly toxic polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF). This study re examines a composite soil sample collected shortly after the fire using state-of the-art FT-ICR (Fourier transform ion cyclotron resonance) and GC * GC-TOF (comprehensive two-dimensional gas chromatography-time-of-flight) mass spectrometry. The FT-ICR experiments led to the identification of approximately 150 molecular formulas, corresponding to chlorinated and mixed chloro/bromo compounds. The majority of these are halogenated polycyclic aromatic hydrocarbons (halo-PAHs), including highly substituted (e.g., C14HCl9 and C16HCl9) and high molecular weight (e.g., C28H12Cl4) Cl-PAHs that have not been reported previously in environmental samples. Complementary GC * GC-TOF experiments resolved individual halo-PAHs, some of which were confirmed with available standards. The concentrations of the most abundant halo-PAH groups, C14H8Cl2 (22 MUg/g) and C16H8Cl2 (20 MUg/g) are much higher than reported dioxin values and comparable to the corresponding PAH groups C14H10 (12 MUg/g) and C16H10 (19 MUg/g). The high abundance of the halo-PAHs identified in this study highlights the need for further investigation into their environmental occurrence and risk. PMID- 25133987 TI - Seeking proxies for internal states in obsessive-compulsive disorder. AB - Pervasive doubts are a central feature of obsessive-compulsive disorder (OCD). We have theorized that obsessive doubts can arise in relation to any internal state and lead to compensatory reliance on more discernible substitutes (proxies), including rules and rituals. Previous findings corroborated this hypothesis, but were based on students with high and low OCD tendencies and did not control for anxiety. The present study tested our hypothesis in OCD participants using both anxiety disorders and nonclinical controls. Twenty OCD participants, 20 anxiety disorders participants, and 20 nonclinical participants underwent 2 experimental procedures. In the first, participants had to produce specific levels of muscle tension with and without the aid of biofeedback. In the second, participants were asked to subjectively assess their own muscle tension after viewing preprogrammed false feedback showing either increasing or decreasing levels of muscle tension. As predicted, OCD participants were less accurate than anxiety disorder and nonclinical participants in producing designated levels of muscle tension when biofeedback was not available and more likely to request the biofeedback when given the opportunity to do so. In the false feedback procedure, OCD participants were more influenced by the false biofeedback when judging their own level of muscle tension compared with the 2 controls groups. In both procedures, anxiety disorder participants did not differ from the nonclinical controls. These results support the hypothesis that individuals with OCD have attenuated access to and reduced confidence in their internal states, and that this deficit is specific to OCD and not attributable to anxiety. PMID- 25133986 TI - Do people with schizophrenia have difficulty anticipating pleasure, engaging in effortful behavior, or both? AB - Motivation deficits are common in schizophrenia, but little is known about underlying mechanisms, or the specific goals that people with schizophrenia set in daily life. Using neurobiological heuristics of pleasure anticipation and effort assessment, we examined the quality of activities and goals of 47 people with and 41 people without schizophrenia, utilizing ecological momentary assessment. Participants were provided cell phones and called 4 times a day for 7 days, and were asked about their current activities and anticipation of upcoming goals. Activities and goals were later coded by independent raters on pleasure and effort. In line with recent laboratory findings on effort computation deficits in schizophrenia, relative to healthy participants, people with schizophrenia reported engaging in less effortful activities and setting less effortful goals, which were related to patient functioning. In addition, patients showed some inaccuracy in estimating how difficult an effortful goal would be, which in turn was associated with lower neurocognition. In contrast to previous research, people with schizophrenia engaged in activities and set goals that were more pleasure-based, and anticipated goals as being more pleasurable than controls. Thus, this study provided evidence for difficulty with effortful behavior and not anticipation of pleasure. These findings may have psychosocial treatment implications, focusing on effort assessment or effort expenditure. For example, to help people with schizophrenia engage in more meaningful goal pursuits, treatment providers may leverage low-effort pleasurable goals by helping patients to break down larger, more complex goals into smaller, lower effort steps that are associated with specific pleasurable rewards. PMID- 25133988 TI - Single water entropy: hydrophobic crossover and application to drug binding. AB - Entropy of water plays an important role in both chemical and biological processes e.g. hydrophobic effect, molecular recognition etc. Here we use a new approach to calculate translational and rotational entropy of the individual water molecules around different hydrophobic and charged solutes. We show that for small hydrophobic solutes, the translational and rotational entropies of each water molecule increase as a function of its distance from the solute reaching finally to a constant bulk value. As the size of the solute increases (0.746 nm), the behavior of the translational entropy is opposite; water molecules closest to the solute have higher entropy that reduces with distance from the solute. This indicates that there is a crossover in translational entropy of water molecules around hydrophobic solutes from negative to positive values as the size of the solute is increased. Rotational entropy of water molecules around hydrophobic solutes for all sizes increases with distance from the solute, indicating the absence of crossover in rotational entropy. This makes the crossover in total entropy (translation + rotation) of water molecule happen at much larger size (>1.5 nm) for hydrophobic solutes. Translational entropy of single water molecule scales logarithmically (Str(QH) = C + kB ln V), with the volume V obtained from the ellipsoid of inertia. We further discuss the origin of higher entropy of water around water and show the possibility of recovering the entropy loss of some hypothetical solutes. The results obtained are helpful to understand water entropy behavior around various hydrophobic and charged environments within biomolecules. Finally, we show how our approach can be used to calculate the entropy of the individual water molecules in a protein cavity that may be replaced during ligand binding. PMID- 25133989 TI - One-step electrodeposited nickel cobalt sulfide nanosheet arrays for high performance asymmetric supercapacitors. AB - A facile one-step electrodeposition method is developed to prepare ternary nickel cobalt sulfide interconnected nanosheet arrays on conductive carbon substrates as electrodes for supercapacitors, resulting in exceptional energy storage performance. Taking advantages of the highly conductive, mesoporous nature of the nanosheets and open framework of the three-dimensional nanoarchitectures, the ternary sulfide electrodes exhibit high specific capacitance (1418 F g(-1) at 5 A g(-1) and 1285 F g(-1) at 100 A g(-1)) with excellent rate capability. An asymmetric supercapacitor fabricated by the ternary sulfide nanosheet arrays as positive electrode and porous graphene film as negative electrode demonstrates outstanding electrochemical performance for practical energy storage applications. Our asymmetric supercapacitors show a high energy density of 60 Wh kg(-1) at a power density of 1.8 kW kg(-1). Even when charging the cell within 4.5 s, the energy density is still as high as 33 Wh kg(-1) at an outstanding power density of 28.8 kW kg(-1) with robust long-term cycling stability up to 50,000 cycles. PMID- 25133990 TI - From micelles to fibers: balancing self-assembling and random coiling domains in pH-responsive silk-collagen-like protein-based polymers. AB - We study the self-assembly of genetically engineered protein-based triblock copolymers consisting of a central pH-responsive silk-like middle block (S(H)n, where S(H) is a silk-like octapeptide, (GA)3GH and n is the number of repeats) flanked by hydrophilic random coil outer blocks (C2). Our previous work has already shown that triblocks with very long midblocks (n = 48) self-assemble into long, stiff protein filaments at pH values where the middle blocks are uncharged. Here we investigate the self-assembly behavior of the triblock copolymers for a range of midblock lengths, n = 8, 16, 24, 48. Upon charge neutralization of S(H)n by adjusting the pH, we find that C2S(H)8C2 and C2S(H)16C2 form spherical micelles, whereas both C2S(H)24C2 and C2S(H)48C2 form protein filaments with a characteristic beta-roll secondary structure of the silk midblocks. Hydrogels formed by C2S(H)48C2 are much stronger and form much faster than those formed by C2S(H)24C2. Enzymatic digestion of much of the hydrophilic outer blocks is used to show that with much of the hydrophilic outer blocks removed, all silk midblocks are capable of self-assembling into stiff protein filaments. In that case, reduction of the steric repulsion by the hydrophilic outer blocks also leads to extensive fiber bundling. Our results highlight the opposing roles of the hydrophilic outer blocks and central silk-like midblocks in driving protein filament formation. They provide crucial information for future designs of triblock protein-based polymers that form stiff filaments with controlled bundling, that could mimick properties of collagen in the extracellular matrix. PMID- 25133991 TI - Modulated protonation of side chain aminoethylene repeats in N-substituted polyaspartamides promotes mRNA transfection. AB - Fine-tuning of chemical structures of polycation-based carriers (polyplexes) is an attractive strategy for safe and efficient mRNA transfaction. Here, mRNA polyplexes comprising N-substituted polyaspartamides with varied numbers of side chain aminoethylene repeats were constructed, and their transfection ability against human hepatoma cells was examined. Transfection efficacy clearly correlated with the number of aminoethylene repeats: polyplexes with odd number repeats (PA-Os) produced sustained increases in mRNA expression compared with those with even number repeats (PA-Es). This predominant efficacy of PA-Os over PA-Es was contradictory to our previous findings for pDNA polyplexes prepared from the same N-substituted polyaspartamides, that is, PA-Es revealed superior transfection efficacy of pDNA than PA-Os. Intracellular FRET analysis using flow cytometry and polyplex tracking under confocal laser scanning microscopy revealed that overall transfection efficacy was determined through the balance between endosomal escaping capability and stability of translocated mRNA in cytoplasm. PA Es efficiently transported mRNA into the cytoplasm. However, their poor cytoplasmic stability led to facile degradation of mRNA, resulting in a less durable pattern of transfection. Alternatively, PA-Os with limited capability of endosomal escape eventually protect mRNA in the cytoplasm to induce sustainable mRNA expression. Higher cytoplasmic stability of pDNA compared to mRNA may shift the limiting step in transfection from cytoplasmic stability to endosomal escape capacity, thereby giving an opposite odd-even effect in transfection efficacy. Endosomal escaping capability and nuclease stability of polyplexes are correlated with the modulated protonation behavior in aminoethylene repeats responding to pH, appealing the substantial importance of chemistry to design polycation structures for promoted mRNA transfection. PMID- 25133993 TI - Pancreatic neoplasm with metastatic workup. PMID- 25133992 TI - High-speed single-particle tracking of GM1 in model membranes reveals anomalous diffusion due to interleaflet coupling and molecular pinning. AB - The biological functions of the cell membrane are influenced by the mobility of its constituents, which are thought to be strongly affected by nanoscale structure and organization. Interactions with the actin cytoskeleton have been proposed as a potential mechanism with the control of mobility imparted through transmembrane "pickets" or GPI-anchored lipid nanodomains. This hypothesis is based on observations of molecular mobility using various methods, although many of these lack the spatiotemporal resolution required to fully capture all the details of the interaction dynamics. In addition, the validity of certain experimental approaches, particularly single-particle tracking, has been questioned due to a number of potential experimental artifacts. Here, we use interferometric scattering microscopy to track molecules labeled with 20-40 nm scattering gold beads with simultaneous <2 nm spatial and 20 MUs temporal precision to investigate the existence and mechanistic origin of anomalous diffusion in bilayer membranes. We use supported lipid bilayers as a model system and demonstrate that the label does not influence time-dependent diffusion in the small particle limit (<=40 nm). By tracking the motion of the ganglioside lipid GM1 bound to the cholera toxin B subunit for different substrates and lipid tail properties, we show that molecular pinning and interleaflet coupling between lipid tail domains on a nanoscopic scale suffice to induce transient immobilization and thereby anomalous subdiffusion on the millisecond time scale. PMID- 25133994 TI - Protective effects of clovamide against H2O2-induced stress in rat cardiomyoblasts H9c2 cell line. AB - Cocoa contains phenolic compounds with known antioxidant and antiradical properties beneficial in different pathologies, including cardiovascular diseases. Herein, we have evaluated the protective effects of clovamide, a minor cocoa component, against oxidative stress induced in the rat cardiomyoblast cell line, also comparing it to its bio-isosteric form, rosmarinic acid, and to the main monomeric flavan-3-ol from low-molecular-weight polyphenol in cocoa, i.e. epicatechin. At nano-micro-molar concentrations, the three compounds inhibited the production of reactive oxygen species and apoptosis, evaluated under different aspects, namely, annexin V positivity, DNA fragmentation, caspase release and activation. These molecules can, thus, be considered for their bioactive beneficial activity in the context of cardiovascular pathologies and, particularly, in the protection towards oxidative stress that follows ischemic injury. Clovamide may, thus, be the primary compound for the development of innovative nutraceutical strategies towards cardiovascular diseases. PMID- 25133995 TI - The real-time method of assessing the contribution of individual sources on visibility degradation in Taichung. AB - Visibility degradation caused by air pollution has become a serious environmental problem in megacities in Northeast Asia. In general, aerosol chemical compositions are measured by a conventional method of time integrated filter sampling for off-line analysis, which cannot represent temporal and spatial variations in the real atmosphere. The in situ air composition measuring equipment, OCEC carbon aerosol analyzer and a long-path visibility transmissometer-3 were used to collect hourly measurements of the soluble ions, organic/elemental carbon, and ambient visibility, respectively. During the observation, two types of weather conditions were identified: transport and stagnant. Because PM2.5 was identified as the predominant species of light extinction, the sources of PM2.5 were determined and investigated using a positive matrix factorization (PMF) analysis. The PMF outputs characterized the six main emission sources (marine/crustal aerosols, secondary nitrate, secondary sulfate, direct vehicle exhaust, coal/incinerator combustion, and local sewage emission) and reconstructed the PM2.5 mass concentrations of each pollutant source in two weather conditions. In addition, the light extinction (bext) was reconstructed using a multivariate linear regression analysis with hourly reconstructed PM2.5 mass concentrations to determine the contributions of each source to bext. The primary results showed that the extinction coefficient was proportional to the PM2.5 with high value in stagnant weather conditions. The secondary sulfate was the most abundant source of bext contribution during the sampling period. In addition, the bext contributions of direct vehicle exhaust and coal/incinerator combustion significantly increased in the stagnant weather condition. According to the results of hourly measurements, this work further emphasized that the sources of direct vehicle exhaust and coal/incinerator combustion in PM2.5 were the important sources of visibility degradation in the stagnant weather conditions, which suggests that the pollutants derived from direct vehicle exhaust and coal/incinerator combustion should be controlled first to improve visibility in Taichung. PMID- 25133996 TI - Knee joint loading in knee osteoarthritis: influence of abdominal and thigh fat. AB - PURPOSE: Using three separate models that included total body mass, total lean and total fat mass, and abdominal and thigh fat as independent measures, we determined their association with knee joint loads in older overweight and obese adults with knee osteoarthritis (OA). METHODS: Fat depots were quantified using computed tomography, and total lean and fat mass were determined with dual energy x-ray absorptiometry in 176 adults (age, 66.3 yr; body mass index, 33.5 kg.m) with radiographic knee OA. Knee moments and joint bone-on-bone forces were calculated using gait analysis and musculoskeletal modeling. RESULTS: Higher total body mass was significantly associated (P <= 0.0001) with greater knee compressive and shear forces, compressive and shear impulses (P < 0.0001), patellofemoral forces (P < 0.006), and knee extensor moments (P = 0.003). Regression analysis with total lean and total fat mass as independent variables revealed significant positive associations of total fat mass with knee compressive (P = 0.0001), shear (P < 0.001), and patellofemoral forces (P = 0.01) and knee extension moment (P = 0.008). Gastrocnemius and quadriceps forces were positively associated with total fat mass. Total lean mass was associated with knee compressive force (P = 0.002). A regression model that included total thigh and total abdominal fat found that both were significantly associated with knee compressive and shear forces (P <= 0.04). Thigh fat was associated with knee abduction (P = 0.03) and knee extension moment (P = 0.02). CONCLUSIONS: Thigh fat, consisting predominately of subcutaneous fat, had similar significant associations with knee joint forces as abdominal fat despite its much smaller volume and could be an important therapeutic target for people with knee OA. PMID- 25133998 TI - Right ventricular fatigue developing during endurance exercise: an exercise cardiac magnetic resonance study. AB - INTRODUCTION: Prolonged intense exercise has often been associated with the impairment of right ventricular (RV) function after activity, whereas this is rare for the left ventricle (LV). The effect of prolonged exercise on the heart has not been adequately measured during exercise itself. METHODS: We performed real-time cardiac magnetic resonance imaging at rest and during incremental exercise in 14 male endurance athletes (mean +/- SD; age = 36 +/- 6 yr, BMI = 23.1 +/- 1.94 kg.m) 1-3 wk before (baseline) and immediately after a 150-km cycling event (end-of-race) to measure LV and RV end-diastolic and end-systolic volumes (EDV and ESV), ejection fraction (EF), and ventricular-arterial coupling (stroke volume [SV]/ESV). RESULTS: End-of-race RV EDV was unchanged from baseline at rest but was significantly increased during near-maximal exercise (235 +/- 18 vs 217 +/- 24 mL, P < 0.0001). Resting RV ESV was higher end-of-race (100 +/- 16 vs 93 +/- 15 mL, P = 0.009), which became more appreciable during near-maximal exercise (75 +/- 15 vs 60 +/- 14 mL, P < 0.0001). RV EF, although unchanged at rest, was significantly decreased during near-maximal exercise (68% +/- 5% vs 73% +/- 4%, P = 0.001). LV volume measures were similar at baseline and end-of-race. Therefore, the effect of endurance activity on the RV and LV was significantly different (P < 0.0001). Cardiac output increased to similar values at near maximal exertion before and at the end of the race. However, whereas LV SV/ESV was unchanged, RV SV/ESV was attenuated end-of-race (P = 0.02 for interaction with race setting). CONCLUSIONS: Intense endurance exercise does not affect LV volume or function but results in RV dilatation and reduced RV EF, which becomes even more significant during exercise. Alterations in RV ventricular-arterial coupling suggest that this may be an expression of exercise-induced RV contractile impairment rather than changes in autonomic or loading conditions. PMID- 25133997 TI - Resistance exercise, disability, and pain catastrophizing in obese adults with back pain. AB - PURPOSE: The purpose of this study was to compare the effects of two different resistance exercise protocols on self-reported disability, fear avoidance beliefs, pain catastrophizing, and back pain symptoms in obese, older adults with low back pain (LBP). METHODS: Obese adults (n = 49, 60-85 yr) with chronic LBP were randomized into a total body resistance exercise intervention (TOTRX), lumbar extensor exercise intervention (LEXT), or a control group (CON). Main outcomes included perceived disability (Oswestry Disability Index, Roland Morris Disability Questionnaire). Psychosocial measures included the Fear Avoidance Beliefs survey, Tampa Scale of Kinesiophobia, and Pain Catastrophizing Scale. LBP severity was measured during three functional tasks: walking, stair climbing, and chair rise using an 11-point numerical pain rating scale. RESULTS: The TOTRX group had greater reductions in self-reported disability scores due to back pain (Oswestry Disability Index, Roland Morris Disability Questionnaire) compared with those in the LEXT (P < 0.05). The Pain Catastrophizing Scale scores decreased in the TOTRX group compared with that in the CON group by month 4 (64.3% vs 4.8%, P < 0.05). Pain severity during chair rise activity and walking was decreased in both the LEXT and TOTRX groups relative to the CON group. CONCLUSIONS: Greater reductions in perceived disability due to LBP can be achieved with TOTRX compared with those achieved with LEXT. Pain catastrophizing and pain severity decreased most with TOTRX. The positive change in psychological outlook may assist obese, older adults with chronic back pain in reconsidering the harmfulness of the pain and facilitate regular participation in other exercise programs. PMID- 25133999 TI - Musculoskeletal risk factors as predictors of injury in community-dwelling women. AB - BACKGROUND: Participating in health-related physical activity (PA) may increase risk for musculoskeletal injury (MSI). PURPOSE: This study aimed to estimate the prevalence of structural/biomechanical risk factors in community-dwelling women and associated risk for incidence of MSI in women who are physically active. METHODS: The Women's Injury study is a surveillance of PA behaviors and MSI in women age 20-83 yr. An orthopedic examination was performed before entry into the study to assess presence of structural/biomechanical risk factors. A total of 886 women completed data collection by reporting weekly PA behavior and MSI for up to 3 yr (2007-2009), with the average participant enrolled for 98 wk. To estimate MSI risk associated with each risk factor separately, time to first MSI was modeled using proportional hazard regression with time-dependent PA covariates, controlling for age, body mass index, and previous injury. RESULTS: Over the course of the study, 236 of the women (26.6%) reported at least one MSI that was PA related. We found a significant association between the number of high flexibility risk factors and PA-related injury at all levels of PA exposure (HR = 1.15 and confidence interval (CI) = 1.04-1.27 for moderate-to-vigorous PA; HR = 1.16 and CI = 1.05-1.28 for moderate PA; HR = 1.15 and CI = 1.04-1.27 for vigorous PA). CONCLUSIONS: When participating at any level of PA for health benefits, women with hypermobility in multiple muscle groups or joints should be watchful for musculoskeletal symptoms and should be counseled not to ignore symptoms when they first occur. PMID- 25134000 TI - Functional overreaching: the key to peak performance during the taper? AB - PURPOSE: The purpose of this study is to examine whether performance supercompensation during taper is maximized in endurance athletes after experiencing overreaching during an overload training (OT) period. METHODS: Thirty-three trained male triathletes were assigned to either OT (n = 23) or normal training groups (n = 10, CTL) during 8 wk. Cycling performance and maximal oxygen uptake (VO2max) were measured after 1 wk of moderate training, a 3-wk period of OT, and then each week during 4-wk taper. RESULTS: Eleven of the 23 subjects from the OT group were diagnosed as functionally overreached (F-OR) after the overload period (decreased performance with concomitant high perceived fatigue), whereas the 12 other subjects were only acutely fatigued (AF) (no decrease in performance). According to qualitative statistical analysis, the AF group demonstrated a small to large greater peak performance supercompensation than the F-OR group (2.6% +/- 1.1%) and the CTL group (2.6% +/- 1.6%). VO2max increased significantly from baseline at peak performance only in the CTL and AF groups. Of the peak performances, 60%, 83%, and 73% occurred within the two first weeks of taper in CTL, AF, and OR, respectively. Ten cases of infection were reported during the study with higher prevalence in F-OR (70%) than that in AF (20%) and CTL (10%). CONCLUSION: This study showed that 1) greater gains in performance and VO2max can be achieved when higher training load is prescribed before the taper but not in the presence of F-OR; 2) peak performance is not delayed during taper when heavy training loads are completed immediately prior; and 3) F-OR provides higher risk for training maladaptation, including increased infection risks. PMID- 25134001 TI - Glucose-fructose enhances performance versus isocaloric, but not moderate, glucose. AB - PURPOSE: The effects of glucose-and-fructose (GF) coingestion on cycling time trial (TT) performance and physiological responses to exercise were examined under postprandial conditions. METHODS: Eight trained male cyclists (age, 25 +/- 6 yr; height, 180 +/- 4 cm; weight, 77 +/- 9 kg; VO2max, 62 +/- 6 mL.kg.min) completed the study. Subjects ingested either an artificially sweetened placebo (PL), a moderate-glucose beverage (MG, 1.03 g.min), a high-glucose beverage (HG, 1.55 g.min), or a GF beverage (1.55 g.min, 2:1 ratio) during approximately 3 h of exercise, including 2 h of constant-load cycling (55% Wmax, 195 +/- 17 W), immediately followed by a computer-simulated 30-km TT. Physiological responses (VE, VO2, RER, HR, blood glucose level, blood lactate level, and RPE) and incidences of gastrointestinal distress were assessed during early (15-20 min), middle (55-60 min), and late exercise (115-120 min) and during the TT. Magnitude based qualitative inferences were used to evaluate differences between treatments. RESULTS: In comparison with that in PL (52.9 +/- 3.7 min), TT performances were faster with GF (50.4 +/- 2.2 min, "very likely" benefit), MG (51.1 +/- 2.4 min, "likely" benefit), and HG (52.0 +/- 3.7 min, "possible" benefit). GF resulted in a "likely" improvement versus HG (3.0%) and an "unclear" effect relative to MG (1.2%). MG was "possibly" beneficial versus HG (1.8%). Few incidences of GI distress were reported in any trials. CONCLUSIONS: GF ingestion seems to enhance performance, relative to PL and HG. However, it is unclear whether GF improves performance versus moderate doses of glucose. PMID- 25134002 TI - Caffeine and performance over consecutive days of simulated competition. AB - PURPOSE: Performance improvements after caffeine (CAF) ingestion are well documented when using a 1-d protocol. In numerous competitions such as the Tour de France, Tour de Ski, world championships, and National College Athletic Association championships, athletes compete for several days in a row. To date, no studies have investigated the effects of CAF when competing for consecutive days in a row. This study aimed to investigate the effects of placebo (PLA) and two different CAF doses (3 and 4.5 mg.kg body mass) on performance in a 10-min all-out, cross-country, double poling ergometer test (C-PT) 2 d in a row. METHOD: Eight highly trained male cross-country skiers (VO2max-run, 78.5 +/- 1.6 mL.kg.min) participated in the study, which was a randomized, double-blind, PLA controlled, crossover design. Performance was assessed as distance covered during a 10-min all-out C-PT. Oral ingestion of CAF or PLA was consumed 75 min before the all-out C-PT. RESULTS: Poling distance was improved after CAF ingestions compared with that after PLA on both days. The improvements on day 1 were 4.0% (90% confidence limits, +/-3.3) and 4.0% +/- 2.9% for both CAF doses, respectively (P < 0.05), whereas improvements on day 2 were 5.0% +/- 3.6% and 5.1% +/- 2.8% for CAF3 and CAF4.5, respectively, compared with those for PLA. Improved performance was associated with increased HR, adrenaline concentration, blood lactate concentration, and VO2 consumption after CAF ingestion. Furthermore, performance was elevated despite higher creatine kinase concentration and muscular pain at arrival on day 2 for both CAF doses. CONCLUSIONS: Both CAF doses improved performance in the 10-min all-out C-PT compared with PLA over two consecutive days. Therefore, CAF seems useful for athletes competing over consecutive days despite higher muscle damage occurring after enhanced performance on the first day. PMID- 25134003 TI - Validation of accelerometer cut points in toddlers with and without cerebral palsy. AB - AIM: The purpose of this study was to validate uni- and triaxial ActiGraph cut points for sedentary time in toddlers with cerebral palsy (CP) and typically developing children (TDC). METHODS: Children (n = 103, 61 boys, mean age = 2 yr, SD = 6 months, range = 1 yr 6 months-3 yr) were divided into calibration (n = 65) and validation (n = 38) samples with separate analyses for TDC (n = 28) and ambulant (Gross Motor Function Classification System I-III, n = 51) and nonambulant (Gross Motor Function Classification System IV-V, n = 25) children with CP. An ActiGraph was worn during a videotaped assessment. Behavior was coded as sedentary or nonsedentary. Receiver operating characteristic-area under the curve analysis determined the classification accuracy of accelerometer data. Predictive validity was determined using the Bland-Altman analysis. RESULTS: Classification accuracy for uniaxial data was fair for the ambulatory CP and TDC group but poor for the nonambulatory CP group. Triaxial data showed good classification accuracy for all groups. The uniaxial ambulatory CP and TDC cut points significantly overestimated sedentary time (bias = -10.5%, 95% limits of agreement [LoA] = -30.2% to 9.1%; bias = -17.3%, 95% LoA = -44.3% to 8.3%). The triaxial ambulatory and nonambulatory CP and TDC cut points provided accurate group-level measures of sedentary time (bias = -1.5%, 95% LoA = -20% to 16.8%; bias = 2.1%, 95% LoA = -17.3% to 21.5%; bias = -5.1%, 95% LoA = -27.5% to 16.1%). CONCLUSION: Triaxial accelerometers provide useful group-level measures of sedentary time in children with CP across the spectrum of functional abilities and TDC. Uniaxial cut points are not recommended. PMID- 25134004 TI - Predicting physical activity energy expenditure in manual wheelchair users. AB - PURPOSE: This study aimed to assess the influence of anatomical placement of an accelerometer on physical activity energy expenditure prediction in manual wheelchair users. METHODS: Ten accelerometer units (ActiGraph GT3X+) were attached to a multiaxis shaker table and subjected to a sinusoidal oscillation procedure to assess mechanical validity and reliability. Fifteen manual wheelchair users (mean +/- SD: age, 36 +/- 11 yr; body mass, 70 +/- 12 kg) then completed five activities, including desk work and wheelchair propulsion (2, 4, 6, and 8 km.h). Expired gases were collected throughout. GT3X+ accelerometers were worn on the right wrist, upper arm, and waist. The relations between physical activity counts and metabolic rate were subsequently assessed, and bias +/- 95% limits of agreement was calculated. RESULTS: During mechanical testing, coefficients of variation ranged from 0.2% to 4.7% (intraunit) and 0.9% to 5.2% (interunit) in all axes. During human exercise testing, physical activity counts at each anatomical location was significantly (P < 0.01) correlated with metabolic rate (wrist, r = 0.93; upper arm, r = 0.87; waist, r = 0.73). The SEE for each correlation were 3.34, 4.38, and 6.07 kJ.min for the wrist, upper arm, and waist, respectively. The absolute bias +/- 95% limits of agreement values were 0.0 +/- 6.5 kJ.min, 0.0 +/- 8.5 kJ.min, and 0.0 +/- 11.8 kJ.min for the wrist, upper arm, and waist, respectively. CONCLUSIONS: The ActiGraph GT3X+ is a reliable tool for determining mechanical movements within the physiological range of human movement. Of the three anatomical locations considered, a wrist-mounted accelerometer explains more of the variance and results in the lowest random error when predicting physical activity energy expenditure in manual wheelchair users. PMID- 25134007 TI - Efficient electrocatalytic oxygen evolution on amorphous nickel-cobalt binary oxide nanoporous layers. AB - Nanoporous Ni-Co binary oxide layers were electrochemically fabricated by deposition followed by anodization, which produced an amorphous layered structure that could act as an efficient electrocatalyst for water oxidation. The highly porous morphologies produced higher electrochemically active surface areas, while the amorphous structure supplied abundant defect sites for oxygen evolution. These Ni-rich (10-40 atom % Co) binary oxides have an increased active surface area (roughness factor up to 17), reduced charge transfer resistance, lowered overpotential (~325 mV) that produced a 10 mA cm(-2) current density, and a decreased Tafel slope (~39 mV decade(-1)). The present technique has a wide range of applications for the preparation of other binary or multiple-metals or metal oxides nanoporous films. Fabrication of nanoporous materials using this method could provide products useful for renewable energy production and storage applications. PMID- 25134005 TI - Predicting human movement with multiple accelerometers using movelets. AB - PURPOSE: The study aims were 1) to develop transparent algorithms that use short segments of training data for predicting activity types and 2) to compare the prediction performance of the proposed algorithms using single accelerometers and multiple accelerometers. METHODS: Sixteen participants (age, 80.6 yr (4.8 yr); body mass index, 26.1 kg.m (2.5 kg.m)) performed 15 lifestyle activities in the laboratory, each wearing three accelerometers at the right hip and left and right wrists. Triaxial accelerometry data were collected at 80 Hz using ActiGraph GT3X+. Prediction algorithms were developed, which, instead of extracting features, build activity-specific dictionaries composed of short signal segments called movelets. Three alternative approaches were proposed to integrate the information from the multiple accelerometers. RESULTS: With at most several seconds of training data per activity, the prediction accuracy at the second level temporal resolution was very high for lying, standing, normal/fast walking, and standing up from a chair (the median prediction accuracy ranged from 88.2% to 99.9% on the basis of the single-accelerometer movelet approach). For these activities, wrist-worn accelerometers performed almost as well as hip-worn accelerometers (the median difference in accuracy between wrist and hip ranged from -2.7% to 5.8%). Modest improvements in prediction accuracy were achieved by integrating information from multiple accelerometers. DISCUSSION AND CONCLUSIONS: It is possible to achieve high prediction accuracy at the second-level temporal resolution with very limited training data. To increase prediction accuracy from the simultaneous use of multiple accelerometers, a careful selection of integrative approaches is required. PMID- 25134009 TI - Tracking of azobenzene isomerization by X-ray emission spectroscopy. AB - Cis-trans isomerizations are among the fundamental processes in photochemistry. In azobenzene or its derivatives this dynamics is, due to its reversibility, one of the reactions widely used in photostimulation of molecular motors or in molecular electronics. Though intensively investigated in the optical regime, no detailed study exists in the X-ray regime so far. Because the X-ray emission spectroscopy echoes the electronic structure sensitive to the geometry, this theoretical report based on the density functional theory and its time-dependent version presents different nitrogen K-edge X-ray emission spectra for cis and trans isomers with close interrelation to their electron configuration. Considering the spectrum along the isomerization path, these structural signatures can be utilized to probe the isomerization dynamics in the excited molecule. The scheme can further be generalized to the element specific photoreactions. PMID- 25134010 TI - Design and synthesis of new stable fluorenyl-based radicals. AB - Organic neutral radicals have long fascinated chemists with a fundamental understanding of structure-reactivity relationships in organic reactions and with applications as new functional materials. However, the elusive nature of these radicals makes the synthesis, isolation, and characterization very challenging. In this work, the synthesis of three long-lived, fluorenyl-based radicals are reported. The geometry and electronic structures of these radicals were systematically investigated with a combination of various experimental methods, besides density functional theory (DFT) calculations, which include X-ray crystallographic analysis, electron spin resonance (ESR), electron nuclear double resonance (ENDOR), cyclic voltammetry, and UV-vis-NIR measurements. Their half life periods (tau(1/2)) in air-saturated solution under ambient conditions were also determined. Surprisingly, all three radicals showed remarkable stabilities: tau(1/2) = 7, 3.5, and 43 days. PMID- 25134008 TI - LC-MS/MS quantitation of esophagus disease blood serum glycoproteins by enrichment with hydrazide chemistry and lectin affinity chromatography. AB - Changes in glycosylation have been shown to have a profound correlation with development/malignancy in many cancer types. Currently, two major enrichment techniques have been widely applied in glycoproteomics, namely, lectin affinity chromatography (LAC)-based and hydrazide chemistry (HC)-based enrichments. Here we report the LC-MS/MS quantitative analyses of human blood serum glycoproteins and glycopeptides associated with esophageal diseases by LAC- and HC-based enrichment. The separate and complementary qualitative and quantitative data analyses of protein glycosylation were performed using both enrichment techniques. Chemometric and statistical evaluations, PCA plots, or ANOVA test, respectively, were employed to determine and confirm candidate cancer-associated glycoprotein/glycopeptide biomarkers. Out of 139, 59 common glycoproteins (42% overlap) were observed in both enrichment techniques. This overlap is very similar to previously published studies. The quantitation and evaluation of significantly changed glycoproteins/glycopeptides are complementary between LAC and HC enrichments. LC-ESI-MS/MS analyses indicated that 7 glycoproteins enriched by LAC and 11 glycoproteins enriched by HC showed significantly different abundances between disease-free and disease cohorts. Multiple reaction monitoring quantitation resulted in 13 glycopeptides by LAC enrichment and 10 glycosylation sites by HC enrichment to be statistically different among disease cohorts. PMID- 25134011 TI - NHC copper(I) complexes bearing dipyridylamine ligands: synthesis, structural, and photoluminescent studies. AB - We describe the synthesis of new cationic tricoordinated copper complexes bearing bidentate pyridine-type ligands and N-heterocyclic carbene as ancillary ligands. These cationic copper complexes were fully characterized by NMR, electrochemistry, X-ray analysis, and photophysical studies in different environments. Density functional theory calculations were also undertaken to rationalize the assignment of the electronic structure and the photophysical properties. These tricoordinated cationic copper complexes possess a stabilizing CH-pi interaction leading to high stability in both solid and liquid states. In addition, these copper complexes, bearing dipyridylamine ligands having a central nitrogen atom as potential anchoring point, exhibit very interesting luminescent properties that render them potential candidates for organic light-emitting diode applications. PMID- 25134012 TI - The effect of the sulfur position on the melting points of lipidic 1-methyl-3 thiaalkylimidazolium ionic liquids. AB - A series of novel lipid-inspired ionic liquids have been synthesized employing the thiol-ene "click" reaction in a single-step process. The thermal properties were determined by differential scanning calorimetry (DSC) and showed observable trends between the C16, C18, and C20 analogues. The minimum melting points for each equivalent chain length series occur at sequential odd sulfur positions, 3, 5, and 7 for the C16, C18, and C20 series, respectively. The magnitude of melting point depression relative to the saturated homologue is observed to have a strong dependence on the position of the sulfur in the side chain. Additionally, the sulfur position corresponding to the lowest melting point for a homologous series shifts further down the chain as the chain length is increased, indicating that the maximum effect takes place near the center of the ion and not the center of the thiaalkyl chain. This synthesis provides tunability and improved thermal stability for 1-methyl-3-thiaalkylimidazolium bistriflimides and insight into structure-property relationships of lipidic ionic liquids. PMID- 25134013 TI - Influence of net energy content of the diets on productive performance and carcass merit of gilts, boars and immunocastrated males slaughtered at 120kg BW. AB - In total, 540 crossbred pigs with an initial body weight of 28.5kg were used to investigate the effects of the net energy (NE) content (2.29, 2.33, 2.37, 2.41 and 2.45 Mcal/kg) of the diet on growth performance and carcass and meat quality traits of gilts, boars and immunocastrated males (IMC). An increase in dietary NE increased NE intake and decreased feed conversion ratio linearly. The IMC pigs showed greater feed intake and average daily gain than gilts and boars. Backfat depth increased and chilled and trimmed ham yield decreased, as the dietary NE increased. Backfat depth was greater for gilts and IMC than for boars. Also, gilts had greater carcass and loin yields than boars and IMC. Diets with the greater NE content were more appropriate for the production of heavy pigs. However, the economic interest of this practice needs further assessment. PMID- 25134014 TI - Differentiation of meat from European wild boars and domestic pigs using polymorphisms in the MC1R and NR6A1 genes. AB - Wild boar meat cannot be easily distinguished from domestic pig meat, especially in processed products, thus it can be fraudulently substituted with cheaper domestic pork. In this study we genotyped polymorphisms in two genes (MC1R, affecting coat color and NR6A1, associated with number of vertebrae) in 293 domestic pigs of five commercial breeds, 111 wild boars sampled in Italy, and 90 in Slovenia and other Western Balkan regions. Allele and genotype frequency data were used to set up a DNA-based method to distinguish meat of wild boars and domestic pigs. Genotyping results indicated that domesticated genes were introgressed into wild boar populations. This complicated the determination of the origin of the meat and would cause a high error rate if markers of only one gene were used. The combined use of polymorphisms in the two analyzed genes substantially reduced false negative results. PMID- 25134016 TI - Steam electrolysis by solid oxide electrolysis cells (SOECs) with proton conducting oxides. AB - Energy crisis and environmental problems caused by the conventional combustion of fossil fuels boost the development of renewable and sustainable energies. H2 is regarded as a clean fuel for many applications and it also serves as an energy carrier for many renewable energy sources, such as solar and wind power. Among all the technologies for H2 production, steam electrolysis by solid oxide electrolysis cells (SOECs) has attracted much attention due to its high efficiency and low environmental impact, provided that the needed electrical power is generated from renewable sources. However, the deployment of SOECs based on conventional oxygen-ion conductors is limited by several issues, such as high operating temperature, hydrogen purification from water, and electrode stability. To avoid these problems, proton-conducting oxides are proposed as electrolyte materials for SOECs. This review paper provides a broad overview of the research progresses made for proton-conducting SOECs, summarizing the past work and finding the problems for the development of proton-conducting SOECs, as well as pointing out potential development directions. PMID- 25134015 TI - Effect of partial reduction of pork meat on the physicochemical and sensory quality of dry ripened sausages: development of a healthy venison salchichon. AB - The minimum percentage of pork meat to be added to traditional venison salchichon has been determined in order to ensure a nutritionally healthier product without impairing physicochemical or sensory properties. Six types of salchichon were made using lean venison and a varying amount of pork meat (40%, 30%, 25%, 20%, 15% and 10%). All types displayed appropriate physicochemical properties (pH, aw, moisture loss) and color (L*, a*, b*) during ripening, as well as adequate levels of lipolysis (acidity index) and lipid oxidation (TBARS). Moreover, reduction of the amount of pork meat in salchichon prompted an increase in the relative percentage of polyunsaturated fatty acids. It was concluded that in making venison salchichon, the addition of a 25% pork meat is sufficient to ensure a satisfactory ripening process and physicochemical characteristics, optimal organoleptic properties and a higher percentage of polyunsaturated fatty acids than that found in traditional venison salchichon. PMID- 25134017 TI - Engineered M13 bacteriophage nanocarriers for intracellular delivery of exogenous proteins to human prostate cancer cells. AB - The size, well-defined structure, and relatively high folding energies of most proteins allow them to recognize disease-relevant receptors that present a challenge to small molecule reagents. While multiple challenges must be overcome in order to fully exploit the use of protein reagents in basic research and medicine, perhaps the greatest challenge is their intracellular delivery to a particular diseased cell. Here, we describe the genetic and enzymatic manipulation of prostate cancer cell-penetrating M13 bacteriophage to generate nanocarriers for the intracellular delivery of functional exogenous proteins to a human prostate cancer cell line. PMID- 25134018 TI - Self-assembly of a Ag nanoparticle-modified and graphene-wrapped TiO2 nanobelt ternary heterostructure: surface charge tuning toward efficient photocatalysis. AB - In recent years, tremendous research efforts have been made towards developing graphene (GR)-based nanocomposites for photocatalytic applications. In this work, surface-coarsened TiO2 nanobelts (SC-TNBs) closely enwrapped with monodispersed Ag nanoparticles (NPs) and GR nanosheets (i.e. Ag/GR/SC-TNBs) were fabricated using a facile self-assembly strategy followed by photoreduction. It was found that the as-prepared Ag/GR/SC-TNBs ternary heterostructure exhibited significantly improved photocatalytic performances under irradiation with UV light in comparison with blank SC-TNBs and its binary counterparts owing to the formation of double heterojunctions among the components. The intimate integration of Ag NPs and GR with SC-TNBs achieved by the self-assembly buildup exerts a profound effect on the transfer of photogenerated electrons over the SC TNBs substrate in which Ag NPs serve as an efficient "electron reservoir" and GR as an electron transporter and collector, thus concurrently prolonging the lifetime of the photogenerated electron-hole pairs and resulting in the remarkably enhanced photoactivity over the Ag/GR/SC-TNBs ternary nanocomposite. In addition, the underlying photocatalytic mechanism was elucidated and the primary active species were determined. PMID- 25134019 TI - Liverpool Active City 2005-2010: Increasing Population Physical Activity Levels Through Intersectoral Action. AB - BACKGROUND: The process of working together across sectors to improve health and to influence its determinants is often referred to as intersectoral action for health. The Liverpool Active City strategy and action plan were launched in 2005, bringing together partners from diverse sectors such as education, transport, and civil society to boost levels of physical activity among the city's residents. METHODS: The research material was based on semistructured interviews with key stakeholders and on review and analysis of gray literature and media reports. A case-study method was used to analyze the experience. RESULTS: The results show that Liverpool Active City succeeded in boosting levels of physical activity among the city's residents and demonstrate how intersectoral action benefited the goals of the program and promoted common aims. CONCLUSIONS: Important lessons can be drawn from the experience of Liverpool Active City for public health professionals and policy makers. Success factors include the involvement of a broad range of agencies from a variety of sectors, which reinforced the sense of partnership in the physical activity agenda and supported the implementation of activities. The experience also demonstrated how intersectoral action brought benefits to the physical activity goals of Liverpool Active City. PMID- 25134020 TI - A novel fluorescent conjugate applicable to visualize the translocation of glucose-fipronil. AB - The ability to visualize the movement of glycosyl insecticides contributes to learning their translocation and distribution in plants. In our present work, a novel fluorescent glucose-fipronil conjugate N-[3-cyano-1-[2,6-dichloro-4 (trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazol-5-yl]-1-(2-[N (7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-beta-D-glucopyranosyl)-1H-1,2,3 triazole-4-methanamine (2-NBDGTF), was obtained via click chemistry. Disk uptake experiments showed that an active carrier-mediated system was involved in the 2 NBDGTF uptake process. Meanwhile, 2-NBDGTF exhibited comparable phloem mobility with GTF in castor bean seedlings. Visualization of 2-NBDGTF uptake and transport experiment showed that this fluorescent glucose-fipronil conjugate could be loaded into sieve tubes after transiting through epidermal cells and mesophyll cells and then translocate from cotyledon to hypocotyl via phloem in castor bean seedlings. The results above determined that it is a promising fluorescence tagging approach for revealing the activities of glycosyl insecticides and 2 NBDGTF is a reasonable and feasible fluorescent surrogate of GTF for tracing the distribution of glucose-fipronil conjugates. PMID- 25134021 TI - An experience sampling study of PTSD and alcohol-related problems. AB - Posttraumatic stress disorder (PTSD) represents a debilitating psychiatric condition that is affecting the lives of many returning veterans. PTSD and alcohol use and dependence are highly comorbid. The purpose of this study was to understand the functional mechanisms between PTSD and alcohol use and problems. Specifically, the role of negative urgency and emotional intelligence were investigated as vulnerability and resiliency factors, respectively. This study utilized experience sampling to test associations between PTSD symptoms and alcohol use and related problems in a sample of 90 OIF/OEF veterans. Participants completed 8 brief questionnaires daily for 2 weeks on palmtop computers. Elevations in PTSD symptoms during the day were associated with subsequent increases in alcohol use and associated problems that night. PTSD symptoms were associated with greater problems above and beyond the effect of drinking level at both the within- and between- person level. Emotional intelligence was associated with lower negative urgency, fewer PTSD symptoms, and less alcohol use and associated problems. The effects of emotional intelligence were primarily indirect via negative urgency and the effects of negative urgency on alcohol use and problems were indirect via its positive association with PTSD symptoms. Hypothesized cross-level effects of emotional intelligence and negative urgency were not supported. The findings suggest a functional association between PTSD symptoms and alcohol consumption. The association between PTSD symptoms and alcohol consumption is consistent with a self-medication model. However, the significant associations between PTSD symptoms and alcohol problems, after controlling for use level, suggest a broader role of dysregulation. PMID- 25134022 TI - Two alternative approaches to conventional person-mean imputation scoring of the Self-Rating of the Effects of Alcohol Scale (SRE). AB - A low level of response to alcohol is considered a significant risk factor for alcohol use disorder. Survey measures of this construct assess the number of drinks required to experience various alcohol effects, so data will be missing for effects participants have not experienced. Furthermore, missingness will likely be more common for items with higher means, as more severe effects are likely experienced both less commonly and at higher consumption levels. We explored whether these atypical characteristics of response-to-alcohol survey data cause problems when using conventional person-mean imputation scoring. This scoring approach involves averaging across nonmissing items for each participant, implicitly assuming that missing items have similar distributional properties (e.g., means) as nonmissing items. Analyses used data from the most commonly utilized response-to-alcohol survey measure: The Self-Rating of the Effects of Alcohol Scale (SRE). Results (a) revealed a strong relationship between higher item means and greater item missingness, (b) established that this relation causes person-mean imputation to produce more downwardly biased response-to alcohol summary scores for participants with more missing data, (c) established that this induced a spurious relationship between higher response-to-alcohol summary scores and higher alcohol-effect endorsement (i.e., the number of SRE alcohol effects experienced), and (d) found that these biases can be reduced with 2 alternative scoring approaches. We discuss these and other potential problems with person-mean imputation, and common and unique advantages of the 2 alternative approaches. We consider generalizability, including how the problems shown here may vary in practical significance across different populations and measures. (PsycINFO Database Record PMID- 25134023 TI - Alcohol-related cues potentiate alcohol impairment of behavioral control in drinkers. AB - The acute impairing effects of alcohol on inhibitory control are well established, and these disinhibiting effects are thought to play a role in its abuse potential. Alcohol impairment of inhibitory control is typically assessed in the context of arbitrary cues, yet drinking environments are comprised of an array of alcohol-related cues that are thought to influence drinking behavior. Recent evidence suggests that alcohol-related stimuli reduce behavioral control in sober drinkers, suggesting that alcohol impairment of inhibitory control might be potentiated in the context of alcohol cues. The current study tested this hypothesis by examining performance on the attentional-bias behavioral activation (ABBA) task that measures the degree to which alcohol-related stimuli can reduce inhibition of inappropriate responses in a between-subjects design. Social drinkers (N = 40) performed the task in a sober condition, and then again following placebo (0.0 g/kg) and a moderate dose of alcohol (0.65 g/kg) in counterbalanced order. Inhibitory failures were greater following alcohol images compared to neutral images in sober drinkers, replicating previous findings with the ABBA task. Moreover, alcohol-related cues exacerbated alcohol impairment of inhibitory control as evidenced by more pronounced alcohol-induced disinhibition following alcohol cues compared to neutral cues. Finally, regression analyses showed that greater alcohol-induced disinhibition following alcohol cues predicted greater self-reported alcohol consumption. These findings have important implications regarding factors contributing to binge or "loss of control" drinking. That is, the additive effect of disrupted control mechanisms via both alcohol cues and the pharmacological effects of the drug could compromise an individual's control over ongoing alcohol consumption. (PsycINFO Database Record PMID- 25134024 TI - Using ecological measures of smoking trigger exposure to predict smoking cessation milestones. AB - This study used ecological momentary assessment data from adult daily smokers attempting to quit smoking to assess relations between exposure to contextual risk factors and cessation failure, latency to a first smoking lapse, or progression from lapse to relapse (smoking 7 days in a row). Participants were adult, daily smokers enrolled in a randomized controlled clinical trial of bupropion SR and individual counseling who were followed to 1 year postquit. Participants reported exposure to high-risk contexts and behaviors, including being where cigarettes were available or smoking was permitted, being around others smoking in prospective, real-time assessment for 2 weeks pre- and 4 weeks postquit. Results showed that greater exposure to contextual risk factors during the prequit did not predict cessation failure. However, Cox regression survival analyses revealed that spending a greater proportion of time where cigarettes were easily available following at least 1 day of abstinence predicted shorter latency to a first lapse, even after controlling for baseline risk factors such as gender, nicotine dependence, depressive symptoms, and living with a smoker. Greater cigarette availability following a lapse was not associated with progression from lapse to relapse with or without baseline risk factors in the model. This suggests that postquit environmental risk factors, such as cigarette availability, increase lapse risk, and stable risk factors, such as living with smokers and higher baseline carbon monoxide level or depressive symptoms, remain potent predictors of progression to relapse. Real-time contextual risk assessments postquit predict lapse above and beyond stable, baseline risk factors. (PsycINFO Database Record PMID- 25134026 TI - Gambling disorder: estimated prevalence rates and risk factors in Macao. AB - An excessive, problematic gambling pattern has been regarded as a mental disorder in the Diagnostic and Statistical Manual for Mental Disorders (DSM) for more than 3 decades (American Psychiatric Association [APA], 1980). In this study, its latest prevalence in Macao (one of very few cities with legalized gambling in China and the Far East) was estimated with 2 major changes in the diagnostic criteria, suggested by the 5th edition of DSM (APA, 2013): (a) removing the "Illegal Act" criterion, and (b) lowering the threshold for diagnosis. A random, representative sample of 1,018 Macao residents was surveyed with a phone poll design in January 2013. After the 2 changes were adopted, the present study showed that the estimated prevalence rate of gambling disorder was 2.1% of the Macao adult population. Moreover, the present findings also provided empirical support to the application of these 2 recommended changes when assessing symptoms of gambling disorder among Chinese community adults. Personal risk factors of gambling disorder, namely being male, having low education, a preference for casino gambling, as well as high materialism, were identified. PMID- 25134027 TI - Anxiety sensitivity as a moderator of the relationship between trait anxiety and illicit substance use. AB - Anxiety and substance use problems are common and often comorbid, and past research has shown that young adults in particular are especially at risk for developing these disorders. To further delineate the relationship between anxiety and substance use, the current study evaluated anxiety sensitivity (AS)-a cognitive vulnerability factor-as a moderator of the association between trait anxiety and illicit substance use in a large sample of young adults (N = 845; M = 18.7 years, SD = 1.0). It was hypothesized that AS would moderate the association between trait anxiety and illicit substance use, such that trait anxiety would significantly predict illicit substance use among those with high, but not low, AS. Consistent with prediction, a significant trait Anxiety * AS interaction was found, chi2(5) = 29.38, p < .001. Specifically, analyses of simple slopes revealed that for the high-AS group, as trait anxiety increased, so did frequency of illicit substance use (odds ratio [OR] = 1.03, p = .005; 95% confidence interval [CI] [1.01, 1.06]). The slope for the low AS was not significant (OR = 0.98, p = .100; 95% CI [0.95, 1.01]). Results also showed significant moderation effects for the AS physical concerns and cognitive concerns facets but not AS social concerns. These findings suggest that AS may be an important cognitive vulnerability that may help to identify those at particular risk for substance use, and that interventions should target AS reduction in anxiety-prone individuals to reduce and prevent substance abuse. PMID- 25134025 TI - Relational aggression, positive urgency and negative urgency: predicting alcohol use and consequences among college students. AB - Research on relational aggression (indirect and social means of inflicting harm) has previously focused on adolescent populations. The current study extends this research by exploring both the frequency of perpetrating and being the target of relational aggression as it relates to alcohol use outcomes in a college population. Further, this study examines whether positive urgency (e.g., acting impulsively in response to positive emotions) and negative urgency (e.g., acting impulsively in response to negative emotions) moderate the relationship between relational aggression and alcohol outcomes. In this study, 245 college students (65.7% female) completed an online survey. Results indicated greater frequency of perpetrating relational aggression, higher levels of positive urgency, or higher levels of negative urgency was associated with more negative consequences. Further, negative urgency moderated the relationship between frequency of perpetrating aggression and consequences such that aggression was more strongly associated with consequences for those high in urgency. Counter to the adolescent literature, the frequency of being the target of aggression was not associated with more alcohol use. These findings suggest that perpetrators of relational aggression may be at particular risk for negative alcohol-related consequences when they act impulsively in response to negative, but not positive, emotions. These students may benefit from interventions exploring alternative ways to cope with negative emotions. PMID- 25134028 TI - A longitudinal analysis of drinking and victimization in college women: is there a reciprocal relationship? AB - The purpose of the current study was to assess the relationship between drinking and severe physical and sexual victimization in a sample of 989 college women over 5 years. Participants completed a Web-based survey each fall semester, beginning as first-time incoming freshman, and continuing each year for 5 years. The survey was comprehensive in assessing drinking, victimization, and relevant covariates. Women were followed whether they remained at university or not. Prior year same type of severe victimization predicted current year victimization, both severe physical and sexual. However, prior year drinking did not predict current year severe victimization. Prior year severe sexual victimization predicted current year drinking. Our findings of a longitudinal relationship between severe sexual victimization and subsequent increases in drinking suggests that college women may be drinking to cope with negative sequelae that they experience as a result of the victimization. We did not find the same longitudinal relationship between drinking and severe physical or sexual victimization, suggesting that a reciprocal relationship does not exist between drinking and victimization among college women. We did find that severe sexual victimization decreased across college, suggesting that the year prior to and the first year of college may be a critical period for intervening to reduce risk for severe victimization. PMID- 25134031 TI - Differential association of drinking motives with alcohol use on weekdays and weekends. AB - Drinking motives (DM) reflect the reasons why individuals drink alcohol. Weekdays are mainly dedicated to work, whereas weekends are generally associated with spending time with friends during special events or leisure activities; using alcohol on weekdays and weekends may also be related to different DM. This study examined whether DM were differentially associated with drinking volume (DV) on weekdays and weekends. A representative sample of 5,391 young Swiss men completed a questionnaire assessing weekday and weekend DV, as well as their DM, namely, enhancement, social, coping, and conformity motives. Associations of DM with weekday and weekend DV were examined using structural equation models. Each DM was tested individually in a separate model; all associations were positive and generally stronger (except conformity) for weekend rather than for weekday DV. Further specific patterns of association were found when DM were entered into a single model simultaneously. Associations with weekday and with weekend DV were positive for enhancement and coping motives. However, associations were stronger with weekend rather than with weekday DV for enhancement, and stronger with weekday than with weekend DV for coping motives. Associations of social motives were not significant with weekend DV and negative with weekday DV. Conformity motives were negatively associated with weekend DV and positively related to weekday DV. These results suggest that interventions targeting enhancement motives should be particularly effective at decreasing weekend drinking, whereas interventions targeted at coping motives would be particularly effective at reducing alcohol use on weekdays. PMID- 25134030 TI - Internalizing and externalizing problem behavior and early adolescent substance use: a test of a latent variable interaction and conditional indirect effects. AB - Externalizing problem behavior is a robust predictor of early adolescent substance use (SU); however, findings regarding internalizing problems have been mixed, suggesting that there may be important moderators of the relationship between internalizing problems and SU. The present study used a community sample (mean age was 12.1 at the first assessment, 55% women, 83% White) to test a longitudinal latent variable interaction structural equation model to examine whether externalizing problems moderated the relationship between internalizing problems and SU. Peer delinquency was tested as a mediator in the model and prior levels of the mediator and outcome were controlled at each wave to establish temporal precedence. Results suggested that (1) internalizing problems were protective against associating with deviant peers, but only at high levels of externalizing symptomatology, (2) higher levels of peer delinquency were associated with increases in SU, and (3) peer delinquency mediated the effect of the problem behavior interaction on SU. Our findings suggest that the impact of internalizing problems on peer delinquency and SU needs to be considered in the context of externalizing problems. Moreover, developmental models involving internalizing symptoms should consider that internalizing symptoms are generally protective against substance use in early adolescence. PMID- 25134029 TI - Childhood stress exposure among preadolescents with and without family histories of substance use disorders. AB - Having a family history of substance use disorders (FH+) increases risk for developing a substance use disorder. This risk may be at least partially mediated by increased exposure to childhood stressors among FH+ individuals. However, measures typically used to assess exposure to stressors are narrow in scope and vary across studies. The nature of stressors that disproportionately affect FH+ children and how these stressors relate to later substance use in this population are not well understood. The purpose of this study was to assess exposure to a broad range of stressors among FH+ and FH- children to better characterize how exposure to childhood stressors relates to increased risk for substance misuse among FH+ individuals. A total of 386 children (305 FH+, 81 FH-; ages 10-12) were assessed using the Stressful Life Events Schedule before the onset of regular substance use. Both the number and severity of stressors were compared. Preliminary follow-up analyses were done for 53 adolescents who subsequently reported initiation of substance use. FH+ children reported more frequent and severe stressors than did FH- children, specifically in the areas of housing, family, school, crime, peers, and finances. Additionally, risk for substance use initiation during early adolescence was influenced directly by having a family history of substance use disorders and also indirectly through increased exposure to stressors among FH+ individuals. In conclusion, FH+ children experience greater stress across multiple domains, which contributes to their risk for substance misuse and related problems during adolescence and young adulthood. (PsycINFO Database Record PMID- 25134032 TI - Self-perceived emerging adult status and substance use. AB - Very little research exists on how self-perceived emerging adult status is associated with substance use among low-income emerging adults. The Inventory of Dimensions of Emerging Adulthood (IDEA) was administered to emerging adults (EAs) ages 18-25 screened for substance use problems (n = l05) in a state-subsidized, not-for-profit treatment agency. We examined whether the defining dimensions of Arnett's (2000a) emerging adulthood theory were associated with substance use frequency and substance-related problems, including: identity exploration, self focus, possibilities, optimism, negativity/instability, and feeling in-between. In multivariate models, feeling in-between was positively associated with substance-related problems. An interaction term between minority status and feeling in-between approached statistical significance (p = .057). Further, IDEA scale score means were comparable to those found in college student samples. Implications for theory revision are discussed. PMID- 25134033 TI - Advantages and disadvantages of college drinking in students' own words: content analysis of the decisional balance worksheet. AB - The decisional balance worksheet (DBW), an open-ended measure of motivation to change, may be used to record the perceived advantages and disadvantages of substance use as well as alternative behaviors. Recent findings have indicated that the open-ended DBW can be quantified to validly reflect college students' level of motivation to reduce their drinking (Collins, Carey, & Otto, 2009). The goal of the current study was to enhance our understanding of college students' perceived advantages and disadvantages of drinking by qualitatively examining the content of their decisional balance. Participants were undergraduate college students at a 4-year university (N = 760) who participated in a randomized controlled trial of online brief motivational interventions. Using the DBW, participants recorded the advantages and disadvantages of their current drinking. Conventional content analysis methods were used to extract common themes. Social, enjoyment, and psychological reasons were the most commonly mentioned advantages of drinking, whereas physical side effects, expense and interference with goals were the most commonly mentioned disadvantages of drinking. These findings show that college students primarily use alcohol for enjoyment, particularly in social situations, as well as for coping with stress and social anxiety. On the other hand, many college students report having physical side effects from drinking as well as other kinds of concerns (e.g., expense, calories). Findings suggest that using the open-ended DBW may result in a more client-centered and accurate representation of what college students perceive as advantages and disadvantages to drinking than established, Likert-scale measures of decisional balance. PMID- 25134034 TI - Profiles of confidence and commitment to change as predictors of moderated drinking: a person-centered approach. AB - Identifying who, among problem drinkers, is best suited for moderation and has the greatest likelihood to control drinking has important public health implications. The current study aimed to identify profiles of problem drinkers who may be more or less successful in moderating drinking within the context of a randomized clinical trial of a brief treatment for alcohol use disorder. A person centered approach was implemented, utilizing composite, baseline daily diary values of confidence and commitment to reduce drinking. Problem drinkers (N = 89) were assessed, provided feedback about their drinking, and randomly assigned to 1 of 3 conditions: 2 brief alcohol use disorder treatments or a third group asked to change on their own. Global self-report assessments were administered at baseline and Week 8 (end of treatment). Daily diary composites were created from data collected via an interactive voice recording system during the week prior to baseline. A K-means cluster analysis identified 3 groups: high, moderate, and low confidence and commitment to change drinking. Group differences were explored, and then group membership was entered into generalized estimating equations to predict drinking trajectories over time. Findings revealed that the groups differentially reduced their drinking, such that the high group had greater reduction in drinking and a faster rate of reduction than the other 2 groups, and the moderate group had greater reduction than the low group. Findings suggest that baseline motivation and self-efficacy are important for predicting prognoses related to successful moderated drinking. Limitations and arenas for future research are discussed. PMID- 25134035 TI - Protective behavioral strategies, alcohol expectancies, and drinking motives in a model of college student drinking. AB - An extensive body of research asserts alcohol expectancies, or beliefs regarding the effects of alcohol, as an important influence on drinking. However, the extent to which expectancies are related to drinking motives and protective behavioral strategies (PBS) has yet to be examined. Existing alcohol mediational models suggest associations between expectancies and drinking motives as well as positive drinking motives and PBS use. Thus, it is possible that drinking motives and PBS use act as intervening factors in the relationship between expectancies and alcohol outcomes. Consequently, the cross-sectional study presented here aimed to test the indirect effect of expectancies (i.e., social facilitation) on alcohol outcomes through drinking motives and PBS use. Participants were 520 (358 female) college student drinkers with a mean age of 20.80 (SD = 4.61) years. Students completed measures of expectancies, drinking motives, PBS use, alcohol use, and alcohol-related problems. Results from structural equation modeling indicated that drinking motives and PBS mediated the relationship between social expectancies and alcohol use. In particular, expectancies were associated with greater positive drinking motives, drinking motives were associated with less PBS use, and PBS was associated with less alcohol use and fewer alcohol-related problems. Given the key role of PBS in explaining drinking outcomes in our model, active efforts to incorporate PBS in alcohol interventions may be particularly beneficial for college students. Further, our findings support the consideration of PBS use as a part of the motivational model of alcohol use in future work. PMID- 25134036 TI - An examination of college student activities and attentiveness during a web delivered personalized normative feedback intervention. AB - Both heavy drinking and related risky sexual behavior among college students are common and are often associated with a number of negative consequences. A previously reported randomized controlled trial showed that a brief personalized normative feedback (PNF) intervention reduced the alcohol consumption and alcohol related risky sexual behavior of heavy drinking, sexually active college students (Lewis et al., 2014). For the present study, we examined what activities students were engaged in when viewing the feedback, as well as who they were with and where they were when receiving the intervention. Furthermore, we conducted supplemental analyses with perceived attentiveness as a hypothesized predictor of change using the same sample (N = 480). Findings indicated that most students were engaged in activities when viewing the feedback and that most students viewed the feedback alone and at home. Furthermore, results revealed PNF to be most effective in reducing drinks per week among participants who reported greater attention. Clinical implications and suggestions for additional research examining how attentiveness can be increased during Web-based interventions are discussed. PMID- 25134037 TI - The influence of self-exempting beliefs and social networks on daily smoking: a mediation relationship explored. AB - The decision to initiate, maintain, or quit cigarette smoking is structured by both social networks and health beliefs. Self-exempting beliefs affect people's decisions in favor of a behavior even when they recognize the harm associated with it. This study incorporated the literatures on social networks and self exempting beliefs to study the problem of daily smoking by exploring their mediatory relationships and the mechanisms of how smoking behavior is developed and maintained. Specifically, this article hypothesizes that social networks affect daily smoking directly as well as indirectly by facilitating the formation of self-exempting beliefs. The sample comes from urban male residents in Hangzhou, China randomly selected and interviewed through multistage sampling in 2011. Using binary mediation analysis with logistic regression to test the hypotheses, the authors found that (a) daily smoking is associated with having smokers in several social network arenas and (b) self-exempting beliefs about smoking mediate the association between coworker network and daily smoking, but not for family network and friend network. The role of social network at work place in the creation and maintenance of self-exempting beliefs should be considered by policymakers, prevention experts, and interventionists. PMID- 25134039 TI - The validity of different measures of automatic alcohol action tendencies. AB - Previous studies have demonstrated that automatic alcohol action tendencies are related to alcohol consumption and hazardous drinking. These action tendencies are measured with reaction time tasks in which the latency to make an approach response to alcohol pictures is compared with the latency to make an avoidance response. In the literature, 4 different tasks have been used, and these tasks differ on whether alcohol is a relevant (R) or irrelevant (IR) feature for categorization and on whether participants must make a symbolic approach response (stimulus-response compatibility [SRC] tasks) or an overt behavioral response (approach avoidance tasks [AAT]) to the pictures. Previous studies have shown positive correlations between measures of action tendencies and hazardous drinking and weekly alcohol consumption. However, results have been inconsistent and the different measures have not been directly compared with each other. Therefore, it is unclear which task is the best predictor of hazardous drinking and alcohol consumption. In the present study, 80 participants completed all 4 measures of action tendencies (i.e., R-SRC, IR-SRC, R-AAT, and IR-AAT) and measures of alcohol consumption and hazardous drinking. Stepwise regressions showed that the R-SRC and R-AAT were the only significant predictors of hazardous drinking, whereas the R-AAT was the only reliable predictor of alcohol consumption. Our results confirm that drinking behavior is positively correlated with automatic alcohol approach tendencies, but only if alcohol-relatedness is the relevant feature for categorization. Theoretical implications and methodological issues are discussed. (PsycINFO Database Record PMID- 25134038 TI - Applying an ensemble classification tree approach to the prediction of completion of a 12-step facilitation intervention with stimulant abusers. AB - The purpose of this study was to explore the selection of predictor variables in the evaluation of drug treatment completion using an ensemble approach with classification trees. The basic methodology is reviewed, and the subagging procedure of random subsampling is applied. Among 234 individuals with stimulant use disorders randomized to a 12-step facilitative intervention shown to increase stimulant use abstinence, 67.52% were classified as treatment completers. A total of 122 baseline variables were used to identify factors associated with completion. The number of types of self-help activity involvement prior to treatment was the predominant predictor. Other effective predictors included better coping self-efficacy for substance use in high-risk situations, more days of prior meeting attendance, greater acceptance of the Disease model, higher confidence for not resuming use following discharge, lower Addiction Severity Index (ASI) Drug and Alcohol composite scores, negative urine screens for cocaine or marijuana, and fewer employment problems. The application of an ensemble subsampling regression tree method utilizes the fact that classification trees are unstable but, on average, produce an improved prediction of the completion of drug abuse treatment. The results support the notion there are early indicators of treatment completion that may allow for modification of approaches more tailored to fitting the needs of individuals and potentially provide more successful treatment engagement and improved outcomes. PMID- 25134040 TI - Does DSM-5 nomenclature for inhalant use disorder improve upon DSM-IV? AB - Among drug classes, substance use disorder (SUD) consequent to using inhalants (SUD-I) has perhaps the smallest evidence base. This study compared DSM-IV versus DSM-5 nomenclatures, testing whether 4 traditional categories of inhalants (aerosols, gases, nitrites, solvents) are manifestations of a single pathology, obtaining item parameters of SUD-I criteria, and presenting evidence that SUD can result from using nitrites. An urban, Midwestern, community sample of 162 inhalant users was recruited. Participants were 2/3 male, nearly 85% White, and had a mean age of 20.3 years (SD = 2.4 years), spanning the ages of greatest incidence of SUD and slightly older than the primary ages of inhalants use initiation. Analyses consisted of bivariate associations, principle components analysis, and item response theory analysis. Validity was demonstrated for SUD-I consequent to each inhalant type as well as for aggregating all inhalant types into a single drug class. Results supported DSM-5 nomenclature over DSM-IV in multiple ways except that occurrence of diagnostic orphans was not statistically smaller using DSM-5. (PsycINFO Database Record PMID- 25134041 TI - The diversion of stimulant medications among a convenience sample of college students with current prescriptions. AB - Diversion is defined as the unlawful channeling of regulated pharmaceuticals from legal sources to the illicit marketplace. Persons with legal prescriptions often give away or sell their medications to others. The misuse of prescription stimulant medications continues to be a problem on college campuses and a need to understand how students are obtaining stimulant medications exists. The object of the study was to identify the prevalence, correlates, and motivations associated with diversion of prescription stimulants among current prescription holders. A large sample of undergraduates (n = 1,022) between the ages of 18 and 24 enrolled at a large public university in the southeastern United States completed an in class questionnaire. Among those respondents, we identified 151 current stimulant prescription holders and analyzed the prevalence, motivations, and correlates associated with lifetime and current diversion. Overall, 58.9% of current prescription holders had given away or sold their stimulant medication during their lifetime. Those with a history of nonmedical use of prescription stimulants were almost 5 times more likely to divert their medication during their lifetime. The majority of those engaging in lifetime and current diversion medication did so infrequently. The most common motivations reported for both lifetime and current diversion were "to make extra money" and to "help during a time of high academic stress." Students who reported a history of prescription misuse were also more likely to engage in current diversion. Diversion-related behaviors should be explored further and programs aimed at the reducing these behaviors should be considered. PMID- 25134042 TI - Associations between childhood adversity, adult stressful life events, and past year drug use disorders in the National Epidemiological Study of Alcohol and Related Conditions (NESARC). AB - Stress sensitization, whereby CA lowers tolerance to later stressors, has been proposed as a potential mechanism explaining the association between exposure to childhood adversities (CA) and drug use disorders in adulthood. However, this mechanism remains untested. This paper begins to address this gap through exploring associations between CA exposure and stressful events in adulthood for predicting drug use disorders. We used data drawn from Wave 2 of the U.S. National Epidemiological Survey of Alcohol and Related Conditions (n = 34,653) to explore whether the association between past-year stressful life events and the 12-month prevalence of disordered cannabis, stimulant, and opiate use varied by the number of types of CA that an individual was exposed to. Past-year stressful life events were associated with an increased risk of cannabis, stimulant, and opiate use disorders among men and women. Exposure to CA was associated with increased risk for disordered cannabis use among men and women and opiate use among men only. Finally, we found significant associations between exposure to CA and past-year stressful life events in predicting disordered drug use, but only for women in relation to disordered stimulant and opiate use. Findings are suggestive of possible stress sensitization effects in predicting disordered stimulant and opiate use among women. Implications of these findings for the prevention and treatment of drug use disorders and for future research are discussed. PMID- 25134043 TI - Assessing sexual motives for drinking alcohol among HIV-positive men who have sex with men. AB - Individuals who drink alcohol for the explicit motive of facilitating or enhancing sex may be more likely to engage in risky sexual behavior, including having sex under the influence of alcohol. However, efforts to assess sexual motives for drinking (SMDs) have been very limited to date. We examined the psychometric properties of a 5-item measure of SMDs in a sample of HIV-positive heavy drinking men who have sex with men. Findings provided excellent support for the scale's internal consistency and concurrent validity with a well-established measure of sexual alcohol expectancies (SAEs). Good discriminant validity was also established, as SMDs were correlated with other drinking motives but uniquely predicted the proportion of sex acts occurring under the influence of alcohol and other drugs, over and above other drinking motives and SAEs. SMDs were not significantly associated with unprotected anal intercourse. Adjusting for alcohol problem severity, higher SMDs were associated with lower willingness to consider changing drinking. Results suggest this measure of SMDs exhibits sound psychometric properties and may be useful in studies examining the association between alcohol use and sexual behavior. (PsycINFO Database Record PMID- 25134045 TI - Implicit identification with drug and alcohol use predicts retention in residential rehabilitation programs. AB - Research has identified numerous factors associated with successful treatment in alcohol and drug rehabilitation programs, yet treatment completion rates are often low and subsequent relapse rates very high. We propose that people's implicit identification with drugs and alcohol may be an additional factor that impacts their ability to complete abstinence-based rehabilitation programs. In the current research, we measured implicit identification with drugs and alcohol using the Implicit Association Test (Greenwald, McGhee, & Schwartz, 1998) among 137 members of a residential rehabilitation program for drugs and alcohol (104 men; mean age = 35 years old, 47 of whom were court-ordered to attend). Implicit identification with drugs and alcohol was measured within 1 week of arrival and again 3 weeks later, prior to the onset of the treatment phase of the program. Duration in rehabilitation was assessed 1 year later. Consistent with predictions, implicit identification with drugs and alcohol predicted the duration that people remained in residential rehabilitation even though a self report measure of identification with drugs and alcohol did not. These results suggest that implicit identification with drugs and alcohol might be an important predictor of treatment outcomes, even among those with serious problems with drug and alcohol use. (PsycINFO Database Record PMID- 25134046 TI - Drinking motives and attentional bias to affective stimuli in problem and non problem drinkers. AB - Problem drinking may reflect a maladaptive means of coping with negative emotions or enhancing positive emotions. Disorders with affective symptoms are often characterized by attentional biases for symptom-congruent emotionally valenced stimuli. Regarding addictions, coping motivated (CM) problem gamblers exhibit an attentional bias for negative stimuli, whereas enhancement motivated (EM) problem gamblers exhibit this bias for positive stimuli (Hudson, Jacques, & Stewart, 2013). We predicted that problem drinkers would show similar motive-congruent attentional biases. Problem and non-problem drinkers (n = 48 per group) completed an emotional orienting task measuring attentional biases to positive, negative, and neutral stimuli. As predicted, EM problem drinkers showed an attentional bias for positive information (i.e., reduced accuracy for positively cued trials). However, CM problem drinkers displayed a general distractibility (i.e., reduced accuracy, regardless of cue valence). The results add further support for Cooper et al.'s (1992) motivational model of alcohol use, and indicate potential motivation-matched intervention targets. (PsycINFO Database Record PMID- 25134044 TI - A retrospective analysis of dissemination biases in the brief alcohol intervention literature. AB - This study examined dissemination and reporting biases in the brief alcohol intervention literature. We used retrospective data from 179 controlled trials included in a meta-analysis on brief alcohol interventions for adolescents and young adults. We examined whether the magnitude and direction of effect sizes were associated with publication type, identification source, language, funding, time lag between intervention and publication, number of reports, journal impact factor, and subsequent citations. Results indicated that effect sizes were larger for studies that had been funded (b = 0.14, 95% confidence interval [CI] [0.04, 0.23]), had a shorter time lag between intervention and publication (b = -0.03, 95% CI [-0.05, -.001]), and were cited more frequently (b = 0.01, 95% CI [+0.00, 0.01]). Studies that were cited more frequently by other authors also had greater odds of reporting positive effects (odds ratio = 1.10, 95% CI [1.02, 1.18]). Results indicated that time lag bias has increased recently: Larger and positive effect sizes were published more quickly in recent years. We found no evidence, however, that the magnitude or direction of effects was associated with location source, language, or journal impact factor. We conclude that dissemination biases may indeed occur in the social and behavioral science literature, as has been consistently documented in the medical literature. As such, primary researchers, journal reviewers, editors, systematic reviewers, and meta-analysts must be cognizant of the causes and consequences of these biases, and commit to engage in ethical research practices that attempt to minimize them. (PsycINFO Database Record PMID- 25134047 TI - Employment-based reinforcement of adherence to oral naltrexone in unemployed injection drug users: 12-month outcomes. AB - Oral naltrexone could be a promising relapse-prevention pharmacotherapy for recently detoxified opioid-dependent patients; however, interventions are often needed to promote adherence with this treatment approach. We recently conducted a study to evaluate a 26-week employment-based reinforcement intervention of oral naltrexone in unemployed injection drug users (Dunn et al., 2013). Participants were randomly assigned into a contingency (n = 35) group required to ingest naltrexone under staff observation to gain entry into a therapeutic workplace or a prescription (n = 32) group given a take-home supply of oral naltrexone and access to the workplace without observed ingestion. Monthly urine samples were collected and analyzed for evidence for naltrexone adherence, opioid use, and cocaine use. As previously reported, contingency participants provided significantly more naltrexone-positive urine samples than prescription participants during the 26-week intervention period. The goal of this current study is to report the 12-month outcomes, which occurred 6 months after the intervention ended. Results at the 12-month visit showed no between-groups differences in naltrexone-positive, opioid-negative, or cocaine-negative urine samples and no participant self-reported using naltrexone at the follow-up visit. These results show that even after a period of successfully reinforced oral naltrexone adherence, longer-term naltrexone use is unlikely to be maintained after reinforcement contingencies are discontinued. (PsycINFO Database Record PMID- 25134048 TI - Couples' marijuana use is inversely related to their intimate partner violence over the first 9 years of marriage. AB - Research on the association between marijuana use and intimate partner violence (IPV) has generated inconsistent findings, and has been primarily based on cross sectional data. We examined whether husbands' and wives' marijuana use predicted both husbands' and wives' IPV perpetration over the first 9 years of marriage (Wave 1, n = 634 couples). We also examined moderation by antisocial behavior, the spouse's marijuana use, and whether IPV was reported during the year before marriage. These predictive associations were calculated using a time-lagged multivariate generalized multilevel model, simultaneously estimating predictors of husband and wife IPV. In fully adjusted models, we found that more frequent marijuana use by husbands and wives predicted less frequent IPV perpetration by husbands. Husbands' marijuana use also predicted less frequent IPV perpetration by wives. Moderation analyses demonstrated that couples in which both spouses used marijuana frequently reported the least frequent IPV perpetration. There was a significant positive association between wives' marijuana use and wives' IPV perpetration, but only among wives who had already reported IPV perpetration during the year before marriage. These findings suggest there may be an overall inverse association between marijuana use and IPV perpetration in newly married couples, although use may be associated with greater risk of perpetration among women with a history of IPV perpetration. PMID- 25134049 TI - Reported planning before and after quitting and quit success: retrospective data from the ITC 4-Country Survey. AB - Planning before quitting smoking is widely believed to be beneficial and is usually recommended in cessation counseling, but there is little evidence on the efficacy of specific planning activities. Using data from 1140 respondents who reported quit attempts at Wave 8 of the ITC 4-Country Survey, we analyzed use of 8 specific planning strategies before (5) and after (3) implementation of a quit attempt, in relation to cessation outcomes, delay in implementation of the attempt, and recent quitting history. Most participants reported some planning both before and after quitting, even among those reporting quitting 'spontaneously.' Younger smokers, those who cut down before quitting, and users of stop-smoking medication were more likely to report planning. Those who planned prequit were also more likely to plan postquit. Unexpectedly, we found no clear benefit of planning on short-term (1 month) cessation outcomes, whereas one prequit strategy (practicing not smoking) was negatively related to outcome. There was evidence for a predicted moderating effect of recent quitting experience on planning for the prequit task 'practice replacement strategies.' This predicted quit success among those with multiple quit attempts in the past year, but failure among those without. This finding suggests that the quality of planning may be critical. More research, particularly on the moderating effect of quit experience, and where measures of planning are collected before outcomes become evident, is needed before clear recommendations can be made on the utility of various forms of planning for the success of quit attempts. PMID- 25134050 TI - Sexual-orientation disparities in substance use in emerging adults: a function of stress and attachment paradigms. AB - More lesbian, gay, and bisexual (LGB) youths than heterosexuals report substance use. We examined a theoretical model to understand these disparities in lifetime and past-year substance use by means of stress and attachment paradigms, using the longitudinal Growing Up Today Study (GUTS) and Nurses' Health Study II (NHSII). GUTS participants are the children of participants in NHSII; thus, child and maternal data are available. In addition, GUTS contains siblings, allowing for comparisons of LGB and heterosexual siblings. Of 5,647 GUTS youths (M = 20.6 years old in 2005), 1.6% were lesbian/gay (LG), 1.6% bisexual (BI), 9.9% mostly heterosexual (MH), and 86.9% completely heterosexual (CH). After adjusting for sibling clustering in GUTS and covariates, significantly more sexual minorities (LGs, BIs, and MHs) than CHs reported lifetime and past-year smoking, nonmarijuana illicit drug use, and prescription drug misuse. More sexual minorities also reported marijuana use in the past year. The relations between sexual orientation and substance use were moderated by the stress markers: As mother's discomfort with homosexuality increased, more BIs and MHs than CHs used substances. As childhood gender nonconforming behaviors increased, more LGs than CHs used substances. The relations between sexual orientation and substance use were mediated by attachment and maternal affection (percent of effect mediated ranged from 5.6% to 16.8%% for lifetime substance use and 4.9% to 24.5% for past year use). In addition, sibling comparisons found that sexual minorities reported more substance use, more childhood gender nonconforming behaviors, and less secure attachment than CH siblings; mothers reported less affection for their sexual minority than CH offspring. The findings indicate the importance of stress and attachment paradigms for understanding sexual-orientation disparities in substance use. PMID- 25134051 TI - Application of item response theory to tests of substance-related associative memory. AB - A substance-related word-association test (WAT) is one of the commonly used indirect tests of substance-related implicit associative memory and has been shown to predict substance use. This study applied an item response theory (IRT) modeling approach to evaluate psychometric properties of the alcohol- and marijuana-related WATs and their items among 775 ethnically diverse at-risk adolescents. After examining the IRT assumptions, item fit, and differential item functioning (DIF) across gender and age groups, the original 18 WAT items were reduced to 14 and 15 items in the alcohol- and marijuana-related WAT, respectively. Thereafter, unidimensional one- and two-parameter logistic models (1PL and 2PL models) were fitted to the revised WAT items. The results demonstrated that both alcohol- and marijuana-related WATs have good psychometric properties. These results were discussed in light of the framework of a unified concept of construct validity (Messick, 1975, 1989, 1995). PMID- 25134052 TI - Drinking to cope among African American college students: an assessment of episode-specific motives. AB - Despite evidence that African Americans are disproportionately affected by drinking to cope relative to European Americans, African American college students' drinking motives remain understudied. Additionally, most research has only examined between-person differences in drinking to cope as a predictor of alcohol use, ignoring within-person variability. In the current daily diary study of 462 African American undergraduates from a historically Black university, associations between episode-specific drinking to cope motives and alcohol use were tested, an approach more consistent with motivational theories of drinking. At baseline, students completed traditional global drinking motive measures; then for 30 days they reported the number of standard drinks they consumed the previous night, and, if they drank, their coping, enhancement, and social reasons for doing so. Students who reported higher mean levels of episode-specific coping motives, on average, consumed more alcohol on drinking evenings. Furthermore, mean episode-specific coping motives, but not global coping motives, predicted average levels of alcohol use. Additionally, coping motives were particularly important for predicting nonsocial (vs. social) drinking. Finally, during evenings for which students reported higher than usual episode-specific coping motives, men consumed more alcohol in both social and nonsocial contexts; in contrast, women reporting higher than usual drinking-to-cope motives only consumed more nonsocial drinks. In conclusion, drinking among African American college students was related to coping motives, particularly among men and in the context of nonsocial alcohol consumption. Moreover, motivational theories of alcohol use may be refined by measuring episode-specific drinking motives that more accurately capture the drinking-to-cope process. PMID- 25134054 TI - The relationship between craving and tobacco use behavior in laboratory studies: a meta-analysis. AB - Published laboratory studies from the last 50 years that included measures of craving and tobacco-consumption or tobacco-seeking measures were included in a meta-analysis in order to assess the relationship between craving and tobacco use. Seeking measures were further subdivided into those that reflected control by nonautomatic and automatic cognitive processes. Of 2,498 articles identified by the initial literature review, 204 analyses from 50 studies were deemed eligible. Overall, the relationship between craving and outcome behaviors was modest (r = .20, p < .001). Studies that imposed abstinence during data collection showed a stronger relationship between craving and outcome (r = .24, p < .001) than studies that did not (r = .18, p < .001). Further, of those studies that reported dependence, the overall association between craving and outcome was stronger for smokers who were less dependent. Separate meta-analyses revealed that the type of outcome measure moderated the omnibus effect, with the relationship between craving and nonautomatic seeking measures (r = .34, p < .001) being stronger than the relationship between craving and automatic seeking/consumption measures (both rs = 0.15, p < .001). These findings suggest that craving may play a role in, but does not fully account for, tobacco-use behaviors; furthermore, the extent to which craving predicts behavior may be increased when the behavior is under nonautomatic cognitive control. PMID- 25134053 TI - Psychiatric correlates of injection risk behavior among young people who inject drugs. AB - People who inject drugs (PWID) and have mental health conditions, such as major depression, an anxiety disorder, or antisocial or borderline personality disorder, may have elevated risk for HIV and HCV infection. This study examined the associations between psychiatric disorders and risky injection behavior in an out-of-treatment sample of young PWID. We recruited participants through outreach and respondent-driven sampling (RDS). Participants completed a computer-assisted self-interview and a psychiatric interview. Interviews took place at a community based field site of the Community Outreach Intervention Projects. Participants were 570 young adults (18 to 25 years) who injected drugs in the previous 30 days. Psychiatric diagnoses were based on interviews using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). Injection behavior was classified into 3 categories: receptive syringe sharing, other equipment sharing only, and no sharing. Associations between injection risk behavior and psychiatric diagnoses were tested using RDS-weighted multinomial regressions. Substance-induced lifetime and past-year major depression, and borderline personality disorder, were significantly associated with a greater likelihood of receptive syringe sharing (p < .001). Substance-induced major depression in the past year was also associated with nonsyringe equipment sharing (p < .01). Primary major depression, antisocial personality disorder, and anxiety disorders other than posttraumatic stress disorder were slightly more prevalent among injectors who shared syringes; however, the associations were not statistically significant. Substance-induced major depression and borderline personality disorder are common among young PWID and are associated with risky injection behavior. PMID- 25134055 TI - Translation of associative learning models into extinction reminders delivered via mobile phones during cue exposure interventions for substance use. AB - Despite experimental findings and some treatment research supporting the use of cues as a means to induce and extinguish cravings, interventions using cue exposure have not been well integrated into contemporary substance abuse treatments. A primary problem with exposure-based interventions for addiction is that after learning not to use substances in the presence of addiction cues inside the clinic (i.e., extinction), stimuli in the naturalistic setting outside the clinic may continue to elicit craving, drug use, or other maladaptive conditioned responses. For exposure-based substance use interventions to be efficacious, new approaches are needed that can prevent relapse by directly generalizing learning from the therapeutic setting into naturalistic settings associated with a high risk for relapse. Basic research suggests that extinction reminders (ERs) can be paired with the context of learning new and more adaptive conditioned responses to substance abuse cues in exposure therapies for addiction. Using mobile phones and automated dialing and data collection software, ERs can be delivered in everyday high-risk settings to inhibit conditioned responses to substance-use-related stimuli. In this review, we describe how associative learning mechanisms (e.g., conditioned inhibition) can inform how ERs are conceptualized, learned, and implemented to prevent substance use when delivered via mobile phones. This approach, exposure with portable reminders of extinction, is introduced as an adjunctive intervention that uses brief automated ERs between clinic visits when individuals are in high-risk settings for drug use. PMID- 25134057 TI - The role of avoidance and inflexibility in characterizing response to contingency management for cocaine use disorders: A secondary profile analysis. AB - Contingency management (CM) is a reinforcement-based approach that provides tangible rewards for objectively verified drug abstinence. CM is the most effective available behavioral intervention for cocaine use disorders; however, response to CM is variable, with significant rates of nonresponse. In the present investigation, we conducted a secondary profile analysis to identify potentially modifiable cognitive-affective characteristics associated with CM response (abstinence vs. continued use) preceding a pharmacotherapy trial for cocaine dependence. Ninety-nine cocaine-dependent, treatment-seeking adults participated in a 4-week baseline CM procedure using high-value vouchers for submission of cocaine-negative urines. Separate profiles for responders and the nonresponders were established using standardized mean scores on relevant pretreatment measures of negative affect, experiential avoidance, cocaine withdrawal/craving, and impulsivity. Results indicated no differences between responder subgroups on baseline levels of negative affect, withdrawal/craving, or impulsivity; however, CM nonresponders, relative to responders, reported significantly higher levels of avoidance and behavioral inflexibility (p < .01) in the context of distressing cocaine-related thoughts, feelings, and bodily sensations. These data suggest that emotion regulation skills may serve as a therapeutic strategy for enhancing response to CM for cocaine use disorders. (PsycINFO Database Record PMID- 25134056 TI - The relationship of therapeutic alliance and treatment delivery fidelity with treatment retention in a multisite trial of twelve-step facilitation. AB - This study examined associations of therapeutic alliance and treatment delivery fidelity with treatment retention in Stimulant Abusers to Engage in Twelve-Step (STAGE-12), a community-based trial of 12-Step Facilitation (TSF) conducted within the National Drug Abuse Treatment Clinical Trials Network (CTN). The STAGE 12 trial randomized 234 stimulant abusers enrolled in 10 outpatient drug treatment programs to an eight-session, group and individual TSF intervention. During the study, TSF participants rated therapeutic alliance using the Helping Alliance questionnaire-II. After the study, independent raters evaluated treatment delivery fidelity of all TSF sessions on adherence, competence, and therapist empathy. Poisson regression modeling examined relationships of treatment delivery fidelity and therapeutic alliance with treatment retention (measured by number of sessions attended) for 174 participants with complete fidelity and alliance data. Therapeutic alliance (p = .005) and therapist competence (p = .010) were significantly associated with better treatment retention. Therapist adherence was associated with poorer retention in a nonsignificant trend (p = .061). In conclusion, stronger therapeutic alliance and higher therapist competence in the delivery of a TSF intervention were associated with better treatment retention whereas treatment adherence was not. Training and fidelity monitoring of TSF should focus on general therapist skills and therapeutic alliance development to maximize treatment retention. (PsycINFO Database Record PMID- 25134058 TI - Testing the four-factor model of personality vulnerability to alcohol misuse: a three-wave, one-year longitudinal study. AB - The 4-factor model of personality vulnerability identifies 4 personality risk factors for alcohol misuse: hopelessness, anxiety sensitivity, impulsivity, and sensation seeking. These personality traits are associated with distinct mechanisms and motivations for alcohol misuse. Individuals high in hopelessness drink to regulate dysphoric affect, while those high in anxiety sensitivity drink to reduce anxiety and to conform to peer expectations. Individuals high in sensation seeking are highly sensitive to the rewarding properties of alcohol, and misuse alcohol to maximize enjoyment. Impulsivity is a broad risk factor contributing to all drinking motives. We hypothesized that personality vulnerabilities would indirectly predict alcohol quantity and problems through specific drinking motives theorized by the 4-factor model. The present study tested hypotheses using a 3-wave, 1-year longitudinal study of undergraduate drinkers (N = 302). Data were analyzed using multilevel path analysis. Hopelessness and impulsivity were positively related to drinking motives in the expected fashion. Anxiety sensitivity was related to coping-anxiety and conformity motives only in the between-subjects model (partially supporting hypotheses), while sensation seeking was generally unrelated to all drinking motives and alcohol outcomes (failing to support hypotheses). Enhancement motives predicted alcohol quantity and problems at both levels, coping-depression motives predicted alcohol problems at the between-subjects level only, and coping anxiety, conformity, and social motives failed to predict alcohol outcomes beyond other motives. Overall, this study partially supports the 4-factor model, with the strongest support emerging for impulsivity and hopelessness. This study suggests that personality traits such as impulsivity and hopelessness may be important targets in prevention and treatment with undergraduate drinkers. PMID- 25134059 TI - Personality and gambling involvement: a person-centered approach. AB - Individual differences in personality are likely to play an important role in explaining the propensity to gamble. One of the potential roadblocks to elucidating the relation between personality and gambling may be inadequately accounting for the diversity of gambling activities. The goal of the present study was to provide a comprehensive and nuanced portrait of the relation between personality and gambling by taking a multivariate approach to the co-use of multiple gambling activities and employing a broad inventory of potentially relevant personality dimensions. Participants were 4,669 individuals from a national Australian twin registry. Structured interviews including an extensive assessment of gambling behaviors were conducted, and personality questionnaires that included the Multidimensional Personality Questionnaire, the Sensation Seeking Scale, and the Magical Ideation Scale were completed. A latent class analysis of past-year involvement in 10 different gambling activities was performed to classify the participants into 5 groups. Unique personality configurations characterized the 3 more gambling-involved latent classes: (a) low behavioral control in the context of high negative emotionality and magical thinking typified extensive, versatile gamblers at high risk of gambling problems; (b) average behavioral control in the context of high negative emotionality and magical thinking typified those who primarily gambled on non strategic games of chance; (c) low behavioral control in the context of high positive emotionality and low magical ideation typified those who primarily gambled on strategic games of skill. This study illustrates the value of using a multivariate person-centered approach for characterizing the personality correlates of the multifaceted phenomenon that is gambling. PMID- 25134061 TI - Swelling of polyelectrolyte and polyzwitterion brushes by humid vapors. AB - Swelling behavior of polyelectrolyte and polyzwitterion brushes derived from poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) in water vapor is investigated using a combination of neutron and X-ray reflectivity and spectroscopic ellipsometry over a wide range of relative humidity (RH) levels. The extent of swelling depends strongly on the nature of the side-chain chemistry. For parent PDMAEMA, there is an apparent enrichment of water vapor at the polymer/air interface. Despite extensive swelling at high humidity level, no evidence of charge repulsion is found in weak or strong polyelectrolyte brushes. Polyzwitterionic brushes swell to a greater extent than the quaternized brushes studied. However, for RH levels beyond 70%, the polyzwitterionic brushes take up less water molecules, leading to a decline in water volume fraction from the maximum of ~0.30 down to ~0.10. Using a gradient in polymer chain grafting density (sigma), we provide evidence that this behavior stems from the formation of inter- and intramolecular zwitterionic complexes. PMID- 25134062 TI - Clearing common bile duct stones: one size does not fit all. PMID- 25134063 TI - Extrinsic and intrinsic charge trapping at the graphene/ferroelectric interface. AB - The interface between graphene and the ferroelectric superlattice PbTiO3/SrTiO3 (PTO/STO) is studied. Tuning the transition temperature through the PTO/STO volume fraction minimizes the adorbates at the graphene/ferroelectric interface, allowing robust ferroelectric hysteresis to be demonstrated. "Intrinsic" charge traps from the ferroelectric surface defects can adversely affect the graphene channel hysteresis and can be controlled by careful sample processing, enabling systematic study of the charge trapping mechanism. PMID- 25134060 TI - The renal dopaminergic system: novel diagnostic and therapeutic approaches in hypertension and kidney disease. AB - Salt sensitivity of blood pressure, whether in hypertensive or normotensive subjects, is associated with increased cardiovascular risk and overall mortality. Salt sensitivity can be treated by reducing NaCl consumption. However, decreasing salt intake in some may actually increase cardiovascular risk, including an increase in blood pressure, that is, inverse salt sensitivity. Several genes have been associated with salt sensitivity and inverse salt sensitivity. Some of these genes encode proteins expressed in the kidney that are needed to excrete a sodium load, for example, dopamine receptors and their regulators, G protein-coupled receptor kinase 4 (GRK4). We review here research in this field that has provided several translational opportunities, ranging from diagnostic tests to gene therapy, such as (1) a test in renal proximal tubule cells isolated from the urine of humans that may determine the salt-sensitive phenotype by analyzing the recruitment of dopamine D1 receptors to the plasma membrane; (2) the presence of common GRK4 gene variants that are not only associated with hypertension but may also be predictive of the response to antihypertensive therapy; (3) genetic testing for polymorphisms of the dopamine D2 receptor that may be associated with hypertension and inverse salt sensitivity and may increase the susceptibility to chronic kidney disease because of loss of the antioxidant and anti-inflammatory effects of the renal dopamine D2 receptor, and (4) in vivo renal selective amelioration of renal tubular genetic defects by a gene transfer approach, using adeno-associated viral vectors introduced to the kidney by retrograde ureteral infusion. PMID- 25134064 TI - Tricyclic pyrazoles part 7. Discovery of potent and selective dihydrothienocyclopentapyrazole derived CB2 ligands. AB - A series of dihydrothienocyclopentapyrazole-based derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The major term, the 6-methyl 1-(1,4-dichlorophenyl)-N-piperidinyl)-1,4-dihydrothieno[2',3'-4,5]cyclopenta[1,2 c]pyrazole-3-carboxamide (6a), displayed a high affinity and good selectivity for CB2 receptors (Ki values of 2.30 nM for CB2 receptor and 440 nM for CB1 receptors respectively). Subsequent analogue preparation resulted in the identification of compounds such as 6b, 6d, 6e, 6k, 6l, 6m, 6s and 6t that showed 1.3-485 fold selectivity for CB2 receptors with potencies in the 1.1-7.2 nM range. These compounds profiled as full agonists at CB2 receptor in an inhibition assay of P ERK 1/2 up regulation in HL-60 cells. PMID- 25134065 TI - Time-resolved spectroscopic and density functional theory study of the photochemistry of Irgacure-2959 in an aqueous solution. AB - The photocleavage reaction mechanism of 2-hydroxy-4'-(2-hydroxyethoxy)-2 methylpropiophenone (Irgacure-2959) was investigated using femtosecond (fs) and nanosecond (ns) transient absorption (-TA) spectroscopy and also picosecond (ps) and nanosecond (ns) time-resolved resonance Raman (-TR(3)) spectroscopy experiments in a water-rich (volume ratio of acetonitrile/water = 3:7) solution. TA spectroscopy was used to study the dynamics of the benzoyl radical growth and decay as well as to investigate the radical quenching process by the radical scavenger methyl acrylate. ps- and ns-TR(3) spectroscopies were employed to monitor the formation of the benzoyl radical and also to characterize its electronic and structural properties. The fs-TA experiments results indicate that the Irgacure-2959 lowest lying excited singlet state S1 underwent efficient intersystem crossing (ISC) to convert into its triplet state with a time constant of 4 ps. Subsequently, this triplet species dissociated into the benzoyl and alkyl radicals with a corresponding maximum absorption band at 415 nm. The TR(3) results in conjunction with results from DFT calculations confirmed that Irgacure 2959 cleaved into the benzoyl and alkyl radicals at a fast rate on the tens of picosecond time scale. PMID- 25134067 TI - Circulating PCSK9 levels correlate with the serum LDL cholesterol level in newborn infants. AB - BACKGROUND AND AIMS: Protein convertase subtilisin/Kexin type-9 (PCSK9) is a substantial player in lipoprotein metabolism. This study was designed to elucidate the role of PCSK9 in the regulation of lipoprotein during the fetal period. STUDY DESIGN AND SUBJECTS: This study was a cross-sectional study. Eighty one neonates (45 males, 36 females) who were admitted to the neonatal intensive care unit were enrolled in the study. The median age in gestational weeks and weight at birth were 37.1 weeks and 2493 g, respectively. There were no gender differences, but the proportion of infants who were small-for-gestational age (SGA) was significantly higher among females than males. The prefed serum PCSK9 level was assayed with ELISA kits. RESULTS: The median PCSK9 concentration in male newborns was significantly lower than that in females (148.2 ng/ml vs. 171.4 ng/ml, respectively, p<0.001). Circulating serum PCSK9 levels were positively correlated with total cholesterol (r=0.281, p<0.05) and low-density lipoprotein cholesterol (LDL-C; r=0.272, p<0.05). However, there were no correlations between PCSK9 levels and birth weight, gestational age or SGA. Multivariate forward stepwise linear regression analysis revealed that gestational age and circulating PCSK9 levels were independent predictors of the serum LDL-C levels in newborn infants. CONCLUSION: Our first quantitative analysis of neonatal serum PCSK9 levels at birth showed that circulating PCSK9 levels show gender-based differences and are significantly correlated with LDL-C. These results suggest that PCSK9 could play an important role in regulating LDL-C levels during the fetal period. PMID- 25134068 TI - Composite photothermal platform of polypyrrole-enveloped Fe3O4 nanoparticle self assembled superstructures. AB - Photothermal nanoplatforms with small size, low cost, multifunctionality, good biocompatibility and in particular biodegradability are greatly desired in the exploration of novel diagnostic and therapeutic methodologies. Despite Fe3O4 nanoparticles (NPs) have been approved as safe clinical agents, the low molar extinction coefficient and subsequent poor photothermal performance shed the doubt as effective photothermal materials. In this paper, we demonstrate the fabrication of polypyrrole (PPy)-enveloped Fe3O4 NP superstructures with a spherical morphology, which leads to a 300-fold increase in the molar extinction coefficient. The basic idea is the optimization of Fe3O4 electronic structures. By controlling the self-assembly of Fe3O4 NPs, the diameters of the superstructures are tuned from 32 to 64 nm. This significantly enhances the indirect transition and magnetic coupling of Fe ions, thus increasing the molar extinction coefficient of Fe3O4 NPs from 3.65 * 10(6) to 1.31 * 10(8) M(-1) cm( 1) at 808 nm. The envelopment of Fe3O4 superstructures with conductive PPy shell introduces additional electrons in the Fe3O4 oscillation system, and therewith further enhances the molar extinction coefficient to 1.12 * 10(9) M(-1) cm(-1). As a result, the photothermal performance is greatly improved. Primary cell experiments indicate that PPy-enveloped Fe3O4 NP superstructures are low toxic, and capable to kill Hela cells under near-infrared laser irradiation. Owing to the low cost, good biocompatibility and biodegradability, the PPy-enveloped Fe3O4 NP superstructures are promising photothermal platform for establishing novel diagnostic and therapeutic methods. PMID- 25134066 TI - Fibril elongation by Abeta(17-42): kinetic network analysis of hybrid-resolution molecular dynamics simulations. AB - A critical step of beta-amyloid fibril formation is fibril elongation in which amyloid-beta monomers undergo structural transitions to fibrillar structures upon their binding to fibril tips. The atomic detail of the structural transitions remains poorly understood. Computational characterization of the structural transitions is limited so far to short Abeta segments (5-10 aa) owing to the long time scale of Abeta fibril elongation. To overcome the computational time scale limit, we combined a hybrid-resolution model with umbrella sampling and replica exchange molecular dynamics and performed altogether ~1.3 ms of molecular dynamics simulations of fibril elongation for Abeta17-42. Kinetic network analysis of biased simulations resulted in a kinetic model that encompasses all Abeta segments essential for fibril formation. The model not only reproduces key properties of fibril elongation measured in experiments, including Abeta binding affinity, activation enthalpy of Abeta structural transitions and a large time scale gap (taulock/taudock = 10(3)-10(4)) between Abeta binding and its structural transitions, but also reveals detailed pathways involving structural transitions not seen before, namely, fibril formation both in hydrophobic regions L17-A21 and G37-A42 preceding fibril formation in hydrophilic region E22-A30. Moreover, the model identifies as important kinetic intermediates strand-loop strand (SLS) structures of Abeta monomers, long suspected to be related to fibril elongation. The kinetic model suggests further that fibril elongation arises faster at the fibril tip with exposed L17-A21, rather than at the other tip, explaining thereby unidirectional fibril growth observed previously in experiments. PMID- 25134069 TI - Active Commuting by Bicycle: Results of an Educational Intervention Study. AB - OBJECTIVE: The objective of this study was to assess the effectiveness of an educational intervention on active commuting by bicycle. METHODS: An intervention study with workers from a metallurgical industry in Santa Catarina state, Brazil was carried out in 2011. A total of 464 individuals were placed in the intervention group (IG) and 468 in the control group (CG). The intervention consisted of strategies based on the transtheoretical model and stages of behavior change. The intervention group took part in activities for 6 months, including 23 meetings. The statistical analysis included intergroup comparison (IG * CG) at baseline and after the intervention. Intragroup analysis was performed 6 months after the intervention. Student's t-test, chi-square, and McNemar tests were used to analyze the data. RESULTS: Of the original total, 876 individuals (94%) participated in the study. The proportion of participants that used bicycles to commute to work (IG) increased significantly from baseline (45.3%) to the final interventional period (47.5%). No difference was found between the CG and the IG group after the interventional period. CONCLUSION: We suggest taking these findings into consideration in further studies to understand better the role of educational intervention on active commuting by bicycle. PMID- 25134070 TI - Posthumous gamete retrieval and reproduction: would the deceased spouse consent? AB - Policy and medical decision-making has been hindered by the absence of reliable data on attitudes toward having one's own gametes retrieved posthumously and used to produce a child in the event of an untimely death. The purpose of this study is to directly and empirically examine whether the presumption against consent is justified in the case of posthumous gamete retrieval following sudden death. Respondents (N=2064) were contacted using a random-digit dialing method that gave every household telephone in the continental United States an equal probability of being contacted, and were asked: "Suppose you were to experience an early death and your spouse wanted to have a biological child with you. Would you or would you not want your spouse to be able to use your sperm/eggs following your death to have a child with you?" Among reproductive age respondents (18-44 years), 70% of males and 58% of females wanted their spouse to be able to use their gametes and, for the most part, attitudes were fairly consistent across demographic characteristics. Religiosity was the best predictor of attitudes- those who described themselves as more religious were less likely to desire posthumous gamete retrieval--but the majority (58%) of respondents who were very religious approved of retrieval. Overall, these data indicate that abandoning the prevailing presumption against consent in favor of a presumption of consent on the part of the deceased will result in the deceased's wishes being honored two and three times more often for females and males, respectively. Three main arguments against a presumption of consent in this context are discussed: autonomy of the deceased, conflict of interest, and the decision-making capacity of a grieving spouse. PMID- 25134071 TI - Parent-adolescent joint projects involving leisure time and activities during the transition to high school. AB - Leisure research to date has generally overlooked planning and organizing of leisure time and activities between parents and adolescents. This investigation examined how a sample of Canadian adolescents and their parents jointly constructed and acted on goals related to adolescents' leisure time during the move from elementary to high school. Using the Qualitative Action-Project Method, data were collected over an 8-10 month period from 26 parent-adolescent dyads located in two urban sites, through video-taped conversations about leisure time, video recall interviews, and telephone monitoring interviews. Analysis of the data revealed that the joint projects of the 26 dyads could be grouped into three clusters: a) governance transfer or attempts to shift, from parent to adolescent, responsibility over academic demands, organizing leisure time, and safety with peers, b) balancing extra-curricular activities with family life, academics, and social activities, and c) relationship adjustment or maintenance. PMID- 25134072 TI - Thinking about the past, present and future in adolescents growing up in Children's Homes. AB - The present study tested the hypothesis that adolescents growing up in Children's Homes differ from adolescents growing up in a family environment in how they think about their past, present and future, in the way they make decisions about future events and rewards, and in their levels of empathy and perspective taking. The participants were 40 adolescents from Children's Homes in Budapest, Hungary, and 40 age- and gender-matched controls. Group differences were found in participants' past and present time perspectives, and girls from Children's Homes showed reduced consistency in their plans for the future. Additionally, gender differences emerged in empathy, perspective taking, and in participants' present and future time perspectives. We discuss the implications of our findings for interventions to improve the future prospects of adolescents in Children's Homes. PMID- 25134073 TI - The differential impact of a classroom-based, alcohol harm reduction intervention, on adolescents with different alcohol use experiences: a multi level growth modelling analysis. AB - While evidence has accumulated suggesting that prevention initiatives may have a limited impact on alcohol use behaviour, reviews suggest that interventions with most potential for behavioural change are interactive and developmental in design. The School Health and Alcohol Harm Reduction Project (SHAHRP) is an example of such an intervention. Researchers are increasingly attempting to understand the differential effects of programmes in population subgroups. The present study is a secondary analysis of data from a non-randomised trial of SHAHRP, a classroom-based alcohol education intervention, involving school children (aged 13-16 years old) in the United Kingdom. Results showed that there were significant positive changes in knowledge about and attitudes towards alcohol in baseline abstainers, supervised drinkers and unsupervised drinkers. Significant positive behavioural effects in terms of amounts consumed, frequency of drinking and self-reported alcohol related harms, were observed almost exclusively among baseline unsupervised drinkers. These behavioural effects support those previously observed in Australia and suggest that the intervention is a viable health promotion tool in the UK. PMID- 25134074 TI - Effects of Active Video Games on Energy Expenditure in Adults: A Systematic Literature Review. AB - BACKGROUND: The objective of this study was to estimate the mean difference in energy expenditure (EE) in healthy adults between playing active video games (AVGs) compared with traditional video games (TVGs) or rest. METHODS: A systematic search was conducted on Ovid MEDLINE, Web of Knowledge, and Academic Search Premier between 1998 and April 2012 for relevant keywords, yielding 15 studies. EE and heart rate (HR) data were extracted, and random effects meta analysis was performed. RESULTS: EE during AVG play was 1.81 (95% CI, 1.29-2.34; I2 = 94.2%) kcal/kg/hr higher, or about 108 kcal higher per hour for a 60-kg person, compared with TVG play. Mean HR was 21 (95% CI, 13.7-28.3; I2 = 93.4%) beats higher per minute during AVG play compared with TVG play. There was wide variation in the EE and HR estimates across studies because different games were evaluated. Overall metabolic equivalent associated with AVG play was 2.62 (95% CI, 2.25-3.00; I2 = 99.2%), equivalent to a light activity level. Most studies had low risk of bias due to proper study design and use of indirect calorimetry to measure EE. CONCLUSION: AVGs may be used to replace sedentary screen time (eg, television watching or TVG play) with light activity in healthy adults. PMID- 25134075 TI - Motor imagery is less efficient in adults with probable developmental coordination disorder: evidence from the hand rotation task. AB - The present study aimed to provide preliminary insight into the integrity of motor imagery (MI) in adults with probable developmental coordination disorder (pDCD). Based on a strong body of evidence indicating that paediatric samples of DCD often experience difficulties engaging MI, we hypothesised that young adults with pDCD would demonstrate similar difficulties. The performance of 12 young adults (19-35 years) with pDCD was compared to 47 age-matched controls on a traditional mental hand rotation task. Mean inverse efficiency scores were generated for each participant by dividing each participant's mean RT by their proportion of correct responses at each of the stimuli presentation conditions. Preliminary analysis revealed that the performance profiles of individuals with pDCD and age-matched controls showed evidence of being constrained by the biomechanical and postural constraints of real movement, suggesting that both groups engaged in an embodied (MI) strategy to complete the task. Despite engaging in a MI strategy, however, young adults with pDCD were nonetheless significantly less efficient when doing so, shown by significant main effects for group on all group efficiency comparisons. Based on the assumption that MI provides insight into the internal 'neural' action representation that precedes action, we argue that the less efficient MI performance demonstrated by young adults with pDCD may indicate inefficiencies engaging or implementing internal action representations. Implications and directions for future research are discussed. PMID- 25134076 TI - Differences between late preterm and full-term infants: comparing effects of a short bout of practice on early reaching behavior. AB - This study compared the effects of a short bout of practice on reaching behavior between late preterm and full-term infants at the onset of goal-directed reaching. Twelve late preterm infants and twelve full-term infants received reaching practice based on a serial schedule. Late preterm and full-term infants were assessed in 3.3+/-1.4 and 2.6+/-1.0 days after the onset of goal-directed reaching in two measures in a single day: immediately before practice (pre-test) and immediately after practice (post-test). During the assessments, the infants were placed in a baby chair and a rubber toy was presented at their midline within reaching distance for 2 min. Between assessments, the infants received practice of toy-oriented reaching in 3 activities repeated for approximately 4 min. The activities were elicited in a pre-established serial sequence and were applied by a physical therapist. During the pre-test, late preterm infants presented lower range of proximal adjustments, greater proportion of reaches with semi-open hand, and greater proportion of reaches without grasping than the full term infants. During the post-test, late preterm infants presented greater motor variability of proximal adjustments, but explored and selected distal control and grasping outcomes less compared to the full-term group. Differences in reaching and gross motor behavior between late preterm and full-term infants can be found at the age of reaching onset. Practice provided new opportunities for late preterm infants to improve perception-action coupling to reach; however, relative to full-terms, they seemed less advanced in benefiting from the experience for more refined manual tasks. PMID- 25134079 TI - Image search reranking with query-dependent click-based relevance feedback. AB - Our goal is to boost text-based image search results via image reranking. There are diverse modalities (features) of images that we can leverage for reranking, however, the effects of different modalities are query-dependent. The primary challenge we face is how to fuse multiple modalities adaptively for different queries, which has often been overlooked in previous reranking research. Moreover, multimodality fusion without an understanding of the query is risky, and may lead to incorrect judgment in reranking. Therefore, to obtain the best fusion weights for the query, in this paper, we leverage click-through data, which can be viewed as an "implicit" user feedback and an effective means of understanding the query. A novel reranking algorithm, called click-based relevance feedback, is proposed. This algorithm emphasizes the successful use of click-through data for identifying user search intention, while leveraging multiple kernel learning algorithm to adaptively learn the query-dependent fusion weights for multiple modalities. We conduct experiments on a real-world data set collected from a commercial search engine with click-through data. Encouraging experimental results demonstrate that our proposed reranking approach can significantly improve the NDCG@10 of the initial search results by 11.62%, and can outperform several existing approaches for most kinds of queries, such as tail, middle, and top queries. PMID- 25134078 TI - Accelerated phase-cycled SSFP imaging with compressed sensing. AB - Balanced steady-state free precession (SSFP) imaging suffers from irrecoverable signal losses, known as banding artifacts, in regions of large B0 field inhomogeneity. A common solution is to acquire multiple phase-cycled images each with a different frequency sensitivity, such that the location of banding artifacts are shifted in space. These images are then combined to alleviate signal loss across the entire field-of-view. Although high levels of artifact suppression are viable using a large number of images, this is a time costly process that limits clinical utility. Here, we propose to accelerate individual acquisitions such that the overall scan time is equal to that of a single SSFP acquisition. Aliasing artifacts and noise are minimized by using a variable density random sampling pattern in k-space, and by generating disjoint sampling patterns for separate acquisitions. A sparsity-enforcing method is then used for image reconstruction. Demonstrations on realistic brain phantom images, and in vivo brain and knee images are provided. In all cases, the proposed technique enables robust SSFP imaging in the presence of field inhomogeneities without prolonging scan times. PMID- 25134080 TI - Advanced screen content coding using color table and index map. AB - This paper presents an advanced screen content coding solution using color table and index map (cTIM) method. This cTIM scheme is implemented in the range extensions of high-efficiency video coding (HEVC-RExt) as an additional tool of intracoding to complement conventional spatial angular prediction to better exploit the screen content redundancy. For each coding unit, a number of major colors will be selected to form the color table, then the original pixel block is translated to the corresponding index map. A 1D or hybrid 1D/2D string match scheme is introduced to derive matched pairs of index map for better compression. Leveraging the color distribution similarity between neighboring image blocks, color table merge is developed to carry it implicitly. For those blocks that color table has to be signaled explicitly, intertable color sharing and intratable color differential predictive coding are applied to reduce the signaling overhead. Extensive experiments have been performed and they have demonstrated the significant coding efficiency improvement over conventional HEVC RExt, resulting in 26%, 18%, and 15% bit rate reduction at lossless case and 23%, 19%, and 13% Bjontegaard Delta-rate improvement at lossy scenario of typical screen content with text and graphics, for respective all intra, random access, and low-delay using B picture encoder settings. Detailed performance study and complexity analysis (as well as the comparison with other algorithms) have been included as well to evidence the efficiency of proposed algorithm. PMID- 25134081 TI - Face super-resolution via multilayer locality-constrained iterative neighbor embedding and intermediate dictionary learning. AB - Based on the assumption that low-resolution (LR) and high-resolution (HR) manifolds are locally isometric, the neighbor embedding super-resolution algorithms try to preserve the geometry (reconstruction weights) of the LR space for the reconstructed HR space, but neglect the geometry of the original HR space. Due to the degradation process of the LR image (e.g., noisy, blurred, and down-sampled), the neighborhood relationship of the LR space cannot reflect the truth. To this end, this paper proposes a coarse-to-fine face super-resolution approach via a multilayer locality-constrained iterative neighbor embedding technique, which intends to represent the input LR patch while preserving the geometry of original HR space. In particular, we iteratively update the LR patch representation and the estimated HR patch, and meanwhile an intermediate dictionary learning scheme is employed to bridge the LR manifold and original HR manifold. The proposed method can faithfully capture the intrinsic image degradation shift and enhance the consistency between the reconstructed HR manifold and the original HR manifold. Experiments with application to face super resolution on the CAS-PEAL-R1 database and real-world images demonstrate the power of the proposed algorithm. PMID- 25134082 TI - Practical signal-dependent noise parameter estimation from a single noisy image. AB - The additive white Gaussian noise is widely assumed in many image processing algorithms. However, in the real world, the noise from actual cameras is better modeled as signal-dependent noise (SDN). In this paper, we focus on the SDN model and propose an algorithm to automatically estimate its parameters from a single noisy image. The proposed algorithm identifies the noise level function of signal dependent noise assuming the generalized signal-dependent noise model and is also applicable to the Poisson-Gaussian noise model. The accuracy is achieved by improved estimation of local mean and local noise variance from the selected low rank patches. We evaluate the proposed algorithm with both synthetic and real noisy images. Experiments demonstrate that the proposed estimation algorithm outperforms the state-of-the-art methods. PMID- 25134083 TI - Automatic segmentation of mitochondria in EM data using pairwise affinity factorization and graph-based contour searching. AB - In this paper, we investigate the segmentation of closed contours in subcellular data using a framework that primarily combines the pairwise affinity grouping principles with a graph partitioning contour searching approach. One salient problem that precluded the application of these methods to large scale segmentation problems is the onerous computational complexity required to generate comprehensive representations that include all pairwise relationships between all pixels in the input data. To compensate for this problem, a practical solution is to reduce the complexity of the input data by applying an over segmentation technique prior to the application of the computationally demanding strands of the segmentation process. This approach opens the opportunity to build specific shape and intensity models that can be successfully employed to extract the salient structures in the input image which are further processed to identify the cycles in an undirected graph. The proposed framework has been applied to the segmentation of mitochondria membranes in electron microscopy data which are characterized by low contrast and low signal-to-noise ratio. The algorithm has been quantitatively evaluated using two datasets where the segmentation results have been compared with the corresponding manual annotations. The performance of the proposed algorithm has been measured using standard metrics, such as precision and recall, and the experimental results indicate a high level of segmentation accuracy. PMID- 25134084 TI - An assistive control approach for a lower-limb exoskeleton to facilitate recovery of walking following stroke. AB - This paper presents a control approach for a lower-limb exoskeleton intended to facilitate recovery of walking in individuals with lower-extremity hemiparesis after stroke. The authors hypothesize that such recovery is facilitated by allowing the patient rather than the exoskeleton to provide movement coordination. As such, an assistive controller that provides walking assistance without dictating the spatiotemporal nature of joint movement is described here. Following a description of the control laws and finite state structure of the controller, the authors present the results of an experimental implementation and preliminary validation of the control approach, in which the control architecture was implemented on a lower limb exoskeleton, and the exoskeleton implemented in an experimental protocol on three subjects with hemiparesis following stroke. In a series of sessions in which each patient used the exoskeleton, all patients showed substantial single-session improvements in all measured gait outcomes, presumably as a result of using the assistive controller and exoskeleton. PMID- 25134085 TI - FORCe: Fully Online and Automated Artifact Removal for Brain-Computer Interfacing. AB - A fully automated and online artifact removal method for the electroencephalogram (EEG) is developed for use in brain-computer interfacing (BCI). The method (FORCe) is based upon a novel combination of wavelet decomposition, independent component analysis, and thresholding. FORCe is able to operate on a small channel set during online EEG acquisition and does not require additional signals (e.g., electrooculogram signals). Evaluation of FORCe is performed offline on EEG recorded from 13 BCI particpants with cerebral palsy (CP) and online with three healthy participants. The method outperforms the state-of the-art automated artifact removal methods Lagged Auto-Mutual Information Clustering (LAMIC) and Fully Automated Statistical Thresholding for EEG artifact Rejection (FASTER), and is able to remove a wide range of artifact types including blink, electromyogram (EMG), and electrooculogram (EOG) artifacts. PMID- 25134086 TI - Guest editorial. Special section on molecular communication. PMID- 25134087 TI - Real-time emulator for reproducing graded potentials in vertebrate retina. AB - In most parts of the retina, neuronal circuits process visual signals represented by slowly changing membrane potentials, or so-called graded potentials. A feasible approach to speculate about the functional roles of retinal neuronal circuits is to reproduce the graded potentials of retinal neurons in response to natural scenes. In this study, we developed a simulation platform for reproducing graded potentials with the following features: real-time reproduction of retinal neural activities in response to natural scenes, a configurable model structure, and compact hardware. The spatio-temporal properties of neurons were emulated efficiently by a mixed analog-digital architecture that consisted of analog resistive networks and a field-programmable gate array. The neural activities on sustained and transient pathways were emulated from 128 * 128 inputs at 200 frames per second. PMID- 25134088 TI - 30 pJ/b, 67 Mbps, Centimeter-to-Meter Range Data Telemetry With an IR-UWB Wireless Link. AB - This paper reports an energy-efficient, impulse radio ultra wideband (IR-UWB) wireless link operating in 3-5 GHz for data telemetry over centimeter-to-meter range distances at rates extended to tens of Mbps. The link comprises an all digital, integrated transmitter (TX) fabricated in 90 nm 1P/9M CMOS that incorporates a waveform-synthesis pulse generator and a timing generator for on off-keying (OOK) pulse modulation and phase scrambling. The link also incorporates an energy-detection receiver (RX) realized with commercial off-the shelf (COTS) components that performs radio-frequency (RF) filtering, amplification, logarithmic power detection for data demodulation and automatic level control for robust operation in the presence of distance variations. Employing a miniaturized, UWB, chip antenna for the TX and RX, wireless transmission of pseudo-random binary sequence (PRBS) data at rates up to 50 Mbps over 10 cm-1 m is shown. Further, employing a high-gain horn antenna for the RX, wireless transmission of PRBS data at rates up to 67 Mbps over 50 cm-4 m is shown with a TX energy consumption of 30 pJ/b (i.e., power consumption of 2 mW) from 1.2 V. The measured bit error rate (BER) in both cases is < 10(-7) . Results from wireless recording of the background current of a carbon-fiber microelectrode (CFM) in one fast-scan cyclic voltammetry (FSCV) scan using the IR-UWB link are also included, exhibiting excellent match with those obtained from a conventional frequency-shift-keyed (FSK) link at ~433 MHz. PMID- 25134089 TI - An Implantable Versatile Electrode-Driving ASIC for Chronic Epidural Stimulation in Rats. AB - This paper presents the design and testing of an electrode driving application specific integrated circuit (ASIC) intended for epidural spinal cord electrical stimulation in rats. The ASIC can deliver up to 1 mA fully programmable monophasic or biphasic stimulus current pulses, to 13 electrodes selected in any possible configuration. It also supports interleaved stimulation. Communication is achieved via only 3 wires. The current source and the control of the stimulation timing were kept off-chip to reduce the heat dissipation close to the spinal cord. The ASIC was designed in a 0.18- MUm high voltage CMOS process. Its output voltage compliance can be up to 25 V. It features a small core area (<;0.36 mm(2)) and consumes a maximum of 114 MUW during a full stimulation cycle. The layout of the ASIC was developed to be suitable for integration on the epidural electrode array, and two different versions were fabricated and electrically tested. Results from both versions were almost indistinguishable. The performance of the system was verified for different loads and stimulation parameters. Its suitability to drive a passive epidural 12-electrode array in saline has also been demonstrated. PMID- 25134090 TI - A New Fully Differential CMOS Capacitance to Digital Converter for Lab-on-Chip Applications. AB - In this paper, we present a new differential CMOS capacitive sensor for Lab-on Chip applications. The proposed integrated sensor features a DC-input SigmaDelta capacitance to digital converter (CDC) and two reference and sensing microelectrodes integrated on the top most metal layer in 0.35 MUm CMOS process. Herein, we describe a readout circuitry with a programmable clocking strategy using a Charge Based Capacitance Measurement technique. The simulation and experimental results demonstrate a high capacitive dynamic range of 100 fF-110 fF, the sensitivity of 350 mV/fF and the minimum detectable capacitance variation of as low as 10 aF. We also demonstrate and discuss the use of this device for environmental applications through various chemical solvents. PMID- 25134091 TI - FREL: A Stable Feature Selection Algorithm. AB - Two factors characterize a good feature selection algorithm: its accuracy and stability. This paper aims at introducing a new approach to stable feature selection algorithms. The innovation of this paper centers on a class of stable feature selection algorithms called feature weighting as regularized energy-based learning (FREL). Stability properties of FREL using L1 or L2 regularization are investigated. In addition, as a commonly adopted implementation strategy for enhanced stability, an ensemble FREL is proposed. A stability bound for the ensemble FREL is also presented. Our experiments using open source real microarray data, which are challenging high dimensionality small sample size problems demonstrate that our proposed ensemble FREL is not only stable but also achieves better or comparable accuracy than some other popular stable feature weighting methods. PMID- 25134092 TI - Nonlinear Topological Component Analysis: Application to Age-Invariant Face Recognition. AB - We introduce a novel formalism that performs dimensionality reduction and captures topological features (such as the shape of the observed data) to conduct pattern classification. This mission is achieved by: 1) reducing the dimension of the observed variables through a kernelized radial basis function technique and expressing the latent variables probability distribution in terms of the observed variables; 2) disclosing the data manifold as a 3-D polyhedron via the alpha shape constructor and extracting topological features; and 3) classifying a data set using a mixture of multinomial distributions. We have applied our methodology to the problem of age-invariant face recognition. Experimental results obtained demonstrate the efficiency of the proposed methodology named nonlinear topological component analysis when compared with some state-of-the-art approaches. PMID- 25134093 TI - On Equivalence of FIS and ELM for Interpretable Rule-Based Knowledge Representation. AB - This paper presents a fuzzy extreme learning machine (F-ELM) that embeds fuzzy membership functions and rules into the hidden layer of extreme learning machine (ELM). Similar to the concept of ELM that employed the random initialization technique, three parameters of F-ELM are randomly assigned. They are the standard deviation of the membership functions, matrix-C (rule-combination matrix), and matrix-D [don't care (DC) matrix]. Fuzzy if-then rules are formulated by the rule combination Matrix of F-ELM, and a DC approach is adopted to minimize the number of input attributes in the rules. Furthermore, F-ELM utilizes the output weights of the ELM to form the target class and confidence factor for each of the rules. This is to indicate that the corresponding consequent parameters are determined analytically. The operations of F-ELM are equivalent to a fuzzy inference system. Several benchmark data sets and a real world fault detection and diagnosis problem have been used to empirically evaluate the efficacy of the proposed F-ELM in handling pattern classification tasks. The results show that the accuracy rates of F-ELM are comparable (if not superior) to ELM with distinctive ability of providing explicit knowledge in the form of interpretable rule base. PMID- 25134094 TI - Incremental Support Vector Learning for Ordinal Regression. AB - Support vector ordinal regression (SVOR) is a popular method to tackle ordinal regression problems. However, until now there were no effective algorithms proposed to address incremental SVOR learning due to the complicated formulations of SVOR. Recently, an interesting accurate on-line algorithm was proposed for training nu -support vector classification (nu-SVC), which can handle a quadratic formulation with a pair of equality constraints. In this paper, we first present a modified SVOR formulation based on a sum-of-margins strategy. The formulation has multiple constraints, and each constraint includes a mixture of an equality and an inequality. Then, we extend the accurate on-line nu-SVC algorithm to the modified formulation, and propose an effective incremental SVOR algorithm. The algorithm can handle a quadratic formulation with multiple constraints, where each constraint is constituted of an equality and an inequality. More importantly, it tackles the conflicts between the equality and inequality constraints. We also provide the finite convergence analysis for the algorithm. Numerical experiments on the several benchmark and real-world data sets show that the incremental algorithm can converge to the optimal solution in a finite number of steps, and is faster than the existing batch and incremental SVOR algorithms. Meanwhile, the modified formulation has better accuracy than the existing incremental SVOR algorithm, and is as accurate as the sum-of-margins based formulation of Shashua and Levin. PMID- 25134095 TI - Adaptive NN Control of a Class of Nonlinear Systems With Asymmetric Saturation Actuators. AB - In this note, adaptive neural network (NN) control is investigated for a class of uncertain nonlinear systems with asymmetric saturation actuators and external disturbances. To handle the effect of nonsmooth asymmetric saturation nonlinearity, a Gaussian error function-based continuous differentiable asymmetric saturation model is employed such that the backstepping technique can be used in the control design. The explosion of complexity in traditional backstepping design is avoided using dynamic surface control. Using radial basis function NN, adaptive control is developed to guarantee that all the signals in the closed-loop system are semiglobally uniformly ultimately bounded, and the tracking error converges to a small neighborhood of origin by appropriately choosing design constants. The effectiveness of the proposed control is demonstrated in the simulation study. PMID- 25134096 TI - Clause states based configuration checking in local search for satisfiability. AB - Two-mode stochastic local search (SLS) and focused random walk (FRW) are the two most influential paradigms of SLS algorithms for the propositional satisfiability (SAT) problem. Recently, an interesting idea called configuration checking (CC) was proposed to handle the cycling problem in SLS. The CC idea has been successfully used to improve SLS algorithms for SAT, resulting in state-of-the art solvers. Previous CC strategies for SAT are based on neighboring variables, and prove successful in two-mode SLS algorithms. However, this kind of neighboring variables based CC strategy is not suitable for improving FRW algorithms. In this paper, we propose a new CC strategy which is based on clause states. We apply this clause states based CC (CSCC) strategy to both two-mode SLS and FRW paradigms. Our experiments show that the CSCC strategy is effective on both paradigms. Furthermore, our developed FRW algorithms based on CSCC achieve state-of-the-art performance on a broad range of random SAT benchmarks. PMID- 25134097 TI - Rating knowledge sharing in cross-domain collaborative filtering. AB - Cross-domain collaborative filtering (CF) aims to share common rating knowledge across multiple related CF domains to boost the CF performance. In this paper, we view CF domains as a 2-D site-time coordinate system, on which multiple related domains, such as similar recommender sites or successive time-slices, can share group-level rating patterns. We propose a unified framework for cross-domain CF over the site-time coordinate system by sharing group-level rating patterns and imposing user/item dependence across domains. A generative model, say ratings over site-time (ROST), which can generate and predict ratings for multiple related CF domains, is developed as the basic model for the framework. We further introduce cross-domain user/item dependence into ROST and extend it to two real world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity in the target domain, where multiple similar sites are viewed as related CF domains and some items in the target domain depend on their correspondences in the related ones; and 2) ROST (time) for modeling user-interest drift over time, where a series of time-slices are viewed as related CF domains and a user at current time-slice depends on herself in the previous time-slice. All these ROST models are instances of the proposed unified framework. The experimental results show that ROST (sites) can effectively alleviate the sparsity problem to improve rating prediction performance and ROST (time) can clearly track and visualize user-interest drift over time. PMID- 25134098 TI - Operating to remove recurrent colorectal cancer: have we got it right? PMID- 25134099 TI - Anteroposterior left vertebral angiogram. PMID- 25134102 TI - Ecological studies: advantages and disadvantages. PMID- 25134100 TI - Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials. AB - OBJECTIVE: To systematically review and describe currently available approaches to supporting maintenance of weight loss in obese adults and to assess the evidence for the effectiveness of these interventions. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Medline, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials. STUDY SELECTION: Studies were identified through to January 2014. Randomised trials of interventions to maintain weight loss provided to initially obese adults (aged >= 18) after weight loss of >= 5% body weight with long term (>= 12 months) follow-up of weight change (main outcome) were included. STUDY APPRAISAL AND SYNTHESIS: Potential studies were screened independently and in duplicate; study characteristics and outcomes were extracted. Meta-analyses were conducted to estimate the effects of interventions on weight loss maintenance with the inverse variance method and a random effects model. Results are presented as mean differences in weight change, with 95% confidence intervals. RESULTS: 45 trials involving 7788 individuals were included. Behavioural interventions focusing on both food intake and physical activity resulted in an average difference of -1.56 kg (95% confidence interval 2.27 to -0.86 kg; 25 comparisons, 2949 participants) in weight regain compared with controls at 12 months. Orlistat combined with behavioural interventions resulted in a -1.80 kg (-2.54 to -1.06; eight comparisons, 1738 participants) difference compared with placebo at 12 months. All orlistat studies reported higher frequencies of adverse gastrointestinal events in the experimental compared with placebo control groups. A dose-response relation for orlistat treatment was found, with 120 mg doses three times a day leading to greater weight loss maintenance (-2.34 kg, -3.03 to -1.65) compared with 60 mg and 30 mg three times a day (-0.70 kg, 95% confidence interval -1.92 to 0.52), P=0.02. CONCLUSIONS: Behavioural interventions that deal with both diet and physical activity show small but significant benefits on weight loss maintenance. PMID- 25134103 TI - Why schools should promote students' health and wellbeing. PMID- 25134101 TI - Quantification of risk factors for herpes zoster: population based case-control study. AB - OBJECTIVES: To quantify the effects of possible risk factors for herpes zoster at different ages. DESIGN: Case-control study. SETTING: UK Clinical Practice Research Datalink primary care data. PARTICIPANTS: 144 959 adults diagnosed with zoster between 2000 and 2011; 549,336 age, sex, and practice matched controls. MAIN OUTCOME MEASURES: Conditional logistic regression was used to generate adjusted odds ratios to estimate the strength of association of each potential risk factor with zoster and assess effect modification by age. RESULTS: The median age of the cases and controls was 62 years. Factors associated with increased risk of zoster included rheumatoid arthritis (3111 (2.1%) v 8029 (1.5%); adjusted odds ratio 1.46, 99% confidence interval 1.38 to 1.55), inflammatory bowel disease (1851 (1.3%) v 5118 (0.9%); 1.36, 1.26 to 1.46), chronic obstructive pulmonary disease (6815 (4.7%) v 20 201 (3.7%); 1.32, 1.27 to 1.37), asthma (10 243 (7.1%) v 31 865 (5.8%); 1.21, 1.17 to 1.25), chronic kidney disease (8724 (6.0%) v 29 437 (5.4%); 1.14, 1.09 to 1.18), and depression (6830 (4.7%) v 22 052 (4.0%); 1.15, 1.10 to 1.20). Type 1, but not type 2, diabetes showed some association with zoster (adjusted odds ratio 1.27, 1.07 to 1.50). The relative effects of many assessed risk factors were larger in younger patients. Patients with severely immunosuppressive conditions were at greatest risk of zoster-for example, patients with lymphoma (adjusted odds ratio 3.90, 3.21 to 4.74) and myeloma (2.16, 1.84 to 2.53), who are not eligible for zoster vaccination. CONCLUSIONS: A range of conditions were associated with increased risk of zoster. In general, the increased risk was proportionally greater in younger age groups. Current vaccines are contraindicated in people at the greatest risk of zoster, highlighting the need for alternative risk reduction strategies in these groups. PMID- 25134104 TI - A student with macrocytic anaemia. PMID- 25134105 TI - AMA data operation makes millions, even monitors non-members. PMID- 25134106 TI - The "Saatchi bill" is mistargeted and will put vulnerable patients at risk. PMID- 25134107 TI - The "Saatchi bill" will cause serious problems for the medical profession. PMID- 25134108 TI - The Saatchi gamble that law will drive creativity in medicine. PMID- 25134109 TI - "Saatchi bill": legal hurdles and clinical irrelevance. PMID- 25134110 TI - Maintenance treatment for adults with chronic asthma. PMID- 25134111 TI - No medical innovation without accessible documentation. PMID- 25134112 TI - Author's reply to Poole, Conway, Bewley, Sundar, and Chalmers and Firkins. PMID- 25134113 TI - The need for initial specialist assessment in suspected dementia. PMID- 25134114 TI - The difficulty and dangers of diagnosing dementia. PMID- 25134115 TI - Power imbalance prevents shared decision making. PMID- 25134116 TI - Financing for health in India. PMID- 25134118 TI - What is a crossover trial? PMID- 25134119 TI - Achieving quality of care in dementia by appropriate and timely diagnosis. PMID- 25134117 TI - Effects of nutritional supplementation for HIV patients starting antiretroviral treatment: randomised controlled trial in Ethiopia. AB - OBJECTIVES: To determine the effects of lipid based nutritional supplements with either whey or soy protein in patients with HIV during the first three months of antiretroviral treatment (ART) and to explore effects of timing by comparing supplementation at the start of ART and after three months delay. DESIGN: Randomised controlled trial. SETTING: Three public ART facilities in Jimma, Oromia region, Ethiopia. PARTICIPANTS: Adults with HIV eligible for ART with body mass index (BMI) >16. INTERVENTION: Daily supplementation with 200 g (4600 kJ) of supplement containing whey or soy during either the first three or the subsequent three months of ART. OUTCOME MEASURES: Primary: lean body mass assessed with deuterium dilution, grip strength measured with dynamometers, and physical activity measured with accelerometer and heart rate monitors. Secondary: viral load and CD4 counts. Auxiliary: weight and CD3 and CD8 counts. RESULTS: Of 318 patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was 19.5 (SD 2.4). At three months, participants receiving the supplements containing whey or soy had increased their lean body mass by 0.85 kg (95% confidence interval 0.16 kg to 1.53 kg) and 0.97 kg (0.29 kg to 1.64 kg), respectively, more than controls. This was accompanied by an increased gain of grip strength of 0.68 kg (-0.11 kg to 1.46 kg) for the whey supplement group and 0.93 kg (0.16 kg to 1.70 kg) for the soy supplement group. There were no effects on physical activity. Total weight gain increased by 2.05 kg (1.12 kg to 2.99 kg) and 2.06 kg (1.14 kg to 2.97 kg) for the whey and soy groups, respectively. In addition, in the whey supplement group overall CD3 counts improved by 150 cells/uL (24 to 275 cells/uL), of which 112 cells/uL (15 to 209 cells/uL) were CD8 and 25 cells/uL ( 2 to 53 cells/uL) were CD4. Effects of the soy containing supplement on immune recovery were not significant. The effects of the two supplements, however, were not significantly different in direct comparison. Exploratory analysis showed that relatively more lean body mass was gained by patients with undetectable viral load at three months. Patients receiving delayed supplementation had higher weight gain but lower gains in functional outcomes. CONCLUSIONS: Lipid based nutritional supplements improved gain of weight, lean body mass, and grip strength in patients with HIV starting ART. Supplements containing whey were associated with improved immune recovery. Trial registration Controlled trials.com ISRCTN32453477. PMID- 25134121 TI - Alistair Burns: slippery when wet. PMID- 25134122 TI - Author's reply to Sleath, Coebergh, and Burns and colleagues. PMID- 25134123 TI - Nutritional survey data are inaccurate. PMID- 25134124 TI - Lack of evidence that saturated fat causes cardiovascular disease. PMID- 25134125 TI - Authors' reply to Winkler and Ravnskov. PMID- 25134126 TI - Collecting data on female genital mutilation. PMID- 25134128 TI - Obesity and lower teenage pregnancy rates. PMID- 25134127 TI - Reception of the "Saatchi bill". PMID- 25134129 TI - The world's deadliest animal. PMID- 25134130 TI - Care of dying review shows shortcomings in palliative care. PMID- 25134131 TI - MPs and peers call for greater patient power. PMID- 25134133 TI - Girl of 13 has the capacity to decide to have an abortion, High Court rules. PMID- 25134132 TI - Newborn babies will be tested for four more disorders, committee decides. PMID- 25134134 TI - Two thirds of British public think spending on NHS should increase. PMID- 25134135 TI - General practice needs investment to provide enhanced services, says BMA. PMID- 25134136 TI - Guidelines underestimate US cervical cancer rates and older women's risk, study finds. PMID- 25134137 TI - Labour would divert L100 m from NHS reorganisation into primary care. PMID- 25134139 TI - Resources for emergency laparotomy vary widely across England and Wales. PMID- 25134140 TI - Researchers commit to greater openness on research involving animals in the UK. PMID- 25134141 TI - Adverse effects of statins. PMID- 25134142 TI - I certified deaths after judicial executions--and I believe capital punishment should be abolished. PMID- 25134143 TI - NHS Choose and Book appointment system will be replaced. PMID- 25134145 TI - Drug development is at risk from proposed takeover of AstraZeneca, MPs are told. PMID- 25134149 TI - Medicare spends billions on "low value" services, US study finds. PMID- 25134147 TI - Hospital ownership of doctors' practices is linked to higher prices and spending, US study finds. PMID- 25134150 TI - Alcohol consumption kills 3.3 million people a year, WHO calculates. PMID- 25134151 TI - New guidance urges NHS commissioners to buy ethically. PMID- 25134152 TI - Merger with AstraZeneca will create a scientific "powerhouse," says Pfizer. PMID- 25134153 TI - US citizens are living longer and consuming more prescription drugs than ever, finds report. PMID- 25134154 TI - Boehringer Ingelheim increases access to clinical trial data. PMID- 25134155 TI - NICE advises certain groups to take daily vitamin D supplement. PMID- 25134163 TI - Transverse ultrasound scan of the upper abdomen. PMID- 25134165 TI - Art in the asylum. PMID- 25134166 TI - James Bell Pettigrew (1832-1908). PMID- 25134167 TI - End-of-life communications. PMID- 25134168 TI - Management of hyperkalaemia. PMID- 25134169 TI - Authors' reply. PMID- 25134171 TI - Radiotherapy should be omitted in most patients. PMID- 25134172 TI - Patients at high risk for recurrence need radiotherapy. PMID- 25134173 TI - Investigation of foot-and-mouth disease outbreaks in the Mbala and Kazungula districts of Zambia. AB - Foot-and-mouth disease (FMD) is an acute, highly contagious viral infection of domestic and wild cloven-hoofed animals. It is known to be endemic in Zambia, with periodic outbreaks occurring in different geographical areas of the country. This study was conducted to investigate the presence of FMD virus (FMDV) in reported FMD-suspected cases in cattle from the Kazungula and Mbala districts of Zambia. Sixty epithelial tissues or oesophageal-pharyngeal (OP) scrapings (probang samples) were collected from Mbala (n = 51) and Kazungula (n = 9) and examined for FMDV. The FMDV viral RNA and serotypes were examined by realtime reverse transcription polymerase chain reaction (qRT-PCR) and antigen Enzyme- linked immunosorbent assay (ELISA), respectively. Twenty-two samples (36.7%) were positive for the FMDV genome by qRT-PCR with Cycle threshold (Ct) values ranging from 13 to 31. The FMDV-positive samples from epithelial tissues showed relatively higher Ct values compared to those obtained from OP scrapings, irrespective of geographical location. Forty percent (40%; n = 4) of epithelial tissues from Mbala were serotyped into SAT 2 serotype by antigen ELISA. Kazungula samples were serotyped into SAT 1. These findings indicated that Mbala and Kazungula districts had FMD outbreaks in 2012 that were ascribed to at least FMDV serotype SAT 2 and SAT 1 field strains. Furthermore, regular interaction between buffalos from the Mosi-o Tunya Park and domestic animals from surrounding areas could contribute to the occurrence of regular FMD outbreaks in Kazungula, whilst the uncontrolled animal movements across borders between Mbala and Nsumbawanga could be responsible for disease outbreaks in Mbala. In-depth molecular biological studies, including sequencing and phylogeny of the viruses, should be conducted to elucidate the complex epidemiology of FMD in Zambia, thereby providing valuable information needed for the rational control strategy of FMD in Zambia and neighbouring countries. PMID- 25134174 TI - Preliminary investigation on presence of peste des petits ruminants in Dakawa, Mvomero district, Morogoro region, Tanzania. AB - Peste des petits ruminants (PPR) is an acute viral disease of small ruminants characterised by the sudden onset of depression, fever, oculonasal discharges, sores in the mouth, foul-smelling diarrhoea and death. For many years, in Africa, the disease was mainly confined to West and Central Africa but it has now spread southwards to previously PPR-free countries including Tanzania, Democratic Republic of Congo and Angola. The disease was first reported in Tanzania in 2008 when it was confined to the Northern Zone districts bordering Kenya. Presence of the disease has also been confirmed in southern Tanzania especially Mtwara region. Recently, a suspected outbreak of PPR in Dakawa area, Mvomero district, Morogoro region was reported. Clinical samples (lungs, intestines, lymph nodes, whole blood and sera) from suspected goats (n = 8) and sheep (n = 1) were submitted to Sokoine University of Agriculture for analysis. Molecular diagnosis by amplification of the nucleoprotein gene and the fusion gene of PPR virus (PPRV) using PPRV specific primers was done. Five goats and the sheep were positive for PPRV after performing RT-PCR. To our knowledge, this is the first report confirming the presence of PPR in the Mvomero district of the Morogoro region, Tanzania. Hence, more efforts should be put in place to prevent the spread of PPR in Tanzania. PMID- 25134175 TI - More treatment is not always better. PMID- 25134176 TI - Transplantation remains significantly underused. PMID- 25134177 TI - The balance is shifting away from screening. PMID- 25134178 TI - The argument for breast cancer screening. PMID- 25134179 TI - Gene dreams. AB - I remember sitting in one of my genetics lectures in the early days of university and being in awe of the complexity of the human being but also at science's ability to probe it. We were in the thick of The Human Genome Project's culmination and all that it promised for the future of medicine. My mind wandered from the nitty-gritty of base pairs to imagine a time when one's personalised blueprint would be an essential tool in the doctor's armament, as commonplace and essential as a full blood examination or electrocardiogram. PMID- 25134180 TI - Overdiagnosis: a necessary part of the learning curve towards excellence. PMID- 25134181 TI - What is the optimal dose of vitamin D? PMID- 25134182 TI - Reply: To PMID 25134181. PMID- 25134183 TI - [Scientific research activities in the Czech surgery]. PMID- 25134184 TI - Look in the mirror. PMID- 25134185 TI - It's just a business decision. PMID- 25134186 TI - The relationship between gamma-glutamyl transferase levels and chronic kidney disease among Appalachian adults. AB - BACKGROUND: Serum gamma-glutamyl transferase (GGT), a marker of oxidative stress has been associated with diabetes and hypertension, which are risk factors for chronic kidney disease (CKD). However, it is unclear whether serum GGT is independently associated with CKD. METHODS: We analyzed data from a population based study of Appalachian adults residing in six communities in Ohio and West Virginia, who were aged > or = 18 years (n = 55,187, 52% women). Serum GGT was examined as gender-specific quintiles (quintiles 1-5 in women: 0-11 U/L, 12-14 U/L, 15-19 U/L, 20-29 U/L and > 29 U/L; quintiles 1-5 in men: 0-17 U/L, 18-23 U/L, 24-30 U/L, 31-45 U/L, and > 45 U/L). The main outcome of interest was CKD (n = 4482), defined as an estimated glomerular filtration rate of < 60 mL/ min/1.73 m2 from serum creatinine. RESULTS: Higher serum GGT levels were not found to be associated with CKD after adjusting for age, education, smoking, alcohol intake, body mass index (BMI), diabetes, hypertension and total cholesterol. In women, compared to quintile 1 of GGT, the odds ratio (OR) (95% confidence interval [CI]) of CKD associated with quintile 5 was 0.93 (0.82-1.06); p-trend = 0.3102. Similarly, in men, compared to quintile 1 of GGT, the odds ratio (OR) (95% confidence interval [CI]) of CKD associated with quintile 5 was 0.94 (0.80-1.10); p-trend = 0.4372. Subgroup analyses that examined the relation between GGT and CKD by alcohol intake and BMI categories also showed a consistent null association. CONCLUSION: In a community-based sample of Appalachian adults, higher serum GGT was not found to be independently associated with CKD. PMID- 25134187 TI - Ectopic production of HCG by a benign ovarian mature cystic teratoma simulating an extra-uterine pregnancy: a case report. AB - Physicians should consider a benign mature cystic teratoma in their differential diagnosis of a patient with an elevated serum human chorionic gonadotropin concentration. BACKGROUND: Following tubal ligation, a woman with amenorrhea and elevated serum human chorionic gonadotropin (HCG) concentrations may be experiencing either an ectopic or an intrauterine pregnancy. Other sources of HCG production can include ovarian germ cell tumors or gestational trophoblastic disease such as a complete or partial molar pregnancy. A rare source of HCG production is a benign mature ovarian teratoma. CASE: A 31-year old Gravida 2 para 2 presented with a positive home pregnancy test three years after she had experienced a Pomeroy tubal ligation. Her serum HCG was 57,914 mlU/mL but a transvaginal ultrasound did not find an intrauterine pregnancy. Laparoscopy was performed due to a suspicion of an ectopic pregnancy and an 11-cm benign mature cystic teratoma (dermoid cyst) within the right ovary was removed. An ectopic pregnancy was not visualized. Post-operatively, her serum HCG levels decreased and were negative within four weeks. CONCLUSION: Mature ovarian cystic teratomas have rarely been reported to secrete HCG. They can be an infrequent source of HCG production and may lead to emergency surgery to treat a suspected extra-uterine pregnancy. PMID- 25134188 TI - Gender and geographic differences in CAD risk factors and CHADS2 scores in atrial fibrillation patients. AB - Atrial fibrillation (AF) is a cardiac arrhythmia associated with a wide range of other co-morbid medical conditions. The state of West Virginia has a higher prevalence of coronary artery disease (CAD) and CAD risk factors compared to the national average. We hypothesized that West Virginians with atrial fibrillation would also have a higher prevalence of CAD risk factors and higher CHADS2 stroke risk scores. This is particularly important since Louisiana is the only high CAD risk southern state included in the original verification of the CHADS2 risk scoring system (i.e. California, Connecticut, Louisiana, Maine, Missouri, New Hampshire, and Vermont). Accordingly, we performed a retrospective analysis of the association between AF and CAD, CAD risk factors and CHADS2 scores in a cohort of men and women in the West Virginia University Hospital population. We report a greater positive association between AF and hypertension, diabetes mellitus and obesity than the national average. AF was seen more commonly among men. But, CHADS2 scores were higher among women as a result of a higher prevalence of diabetes mellitus. This study indicates that AF is associated with a greater prevalence of CAD risk factors and higher CHADS2 scores among West Virginians in comparison with the rest of the nation. PMID- 25134189 TI - Identification of genes contributing to cardiovascular disease in overweight and obese individuals from West Virginia. AB - Excess weight is a known risk factor for coronary artery disease (CAD) and a large percentage of overweight and obese individuals ultimately develop CAD. The objective of this study was to identify human genes associated with CAD in a subgroup of overweight and obese individuals using population-based association methods. Logistic regression analyses were used to test the association between single nucleotide polymorphisms (SNPs) in 34 candidate genes and the CAD phenotype with age, gender, and BMI as covariates. Two SNPs in the Apolipoprotein B (Apo B) gene [rs1042031 and rs1800479], one in the Cholesterol Ester Transfer Protein (CETP) gene [rs5880], and one in the Low Density Lipoprotein Receptor (LDLR) gene [rs2569538] met the 0.01 significance level for association with CAD. Based on these findings, we conclude that variants within the CETP and Apo B genes conferred susceptibility to CAD in overweight individuals and that a variant with the LDLR gene conferred susceptibility in an obese group. PMID- 25134191 TI - In with the new. PMID- 25134190 TI - Strongyloides hyperinfection syndrome complications: a case report and review of the literature. AB - Strongyloidiasis is a major global health challenge that is often underestimated in many countries. In immuno-compromised hosts, an autoinfection can go unchecked with large numbers of invasive Strongyloides larvae disseminating widely and causing hyperinfection, with fatal consequences. This review will highlight a case of gram negative bacteremia complicated by meningitis and Adult Respiratory Distress Syndrome (ARDS) as a fatal outcome of Strongyloides hyperinfection, commonly known to occur in the setting of immunosuppression. A middle aged female with chronic lymphocytic leukemia and hypogammaglobulinemia presented with severe respiratory distress requiring intubation. She had been on intermittent corticosteroids and multiple courses of antibiotics for the past six months for COPD exacerbations. Bronchoalveolar lavage showed Strongyloides stercoralis. Blood cultures grew Vancomycin Resistant Enterococci and a few days later Vancomycin Sensitive Enterococcus was found in the CSF. Afterwards, she grew Vancomycin Sensitive Enterococcus in the blood. She was treated with Ivermectin and Albendazole for Strongyloides and Linezolid and Vancomycin for these two different strains of E. faecium. After initial resolution of bacteremia and meningitis, she relapsed three weeks later with the same organism growing in the CSF. The clinical course continued to deteriorate with the development of significant neurological dysfunction. Poor nutritional state and ventilator associated pneumonia contributed to this downward trend. After a detailed discussion with the family, life support was discontinued and the patient succumbed to her illness. PMID- 25134192 TI - WVU Healthcare welcomes new heart surgeon. Dr. Anthony Holden Joins WVU Heart Institute. PMID- 25134193 TI - WVU Healthcare offers new lung cancer screening program. PMID- 25134194 TI - Meaningful use--becoming a "meaningful user". PMID- 25134195 TI - Translational Genomic Research Institute dedicated. PMID- 25134197 TI - Disability insurance: residual/recovery benefit. PMID- 25134196 TI - Nanoparticles in fuel additives associated with liver damage. PMID- 25134198 TI - Chains and other choices. PMID- 25134199 TI - Induction. NHS can scrimp and save on medicines. PMID- 25134200 TI - Workforce. Pharma on the front line. PMID- 25134201 TI - Workforce. Why the key to people is planning. PMID- 25134202 TI - Patient safety: case studies. Turning confusion to clarity. PMID- 25134203 TI - Clinical care protocols. When safe comes as standard. PMID- 25134204 TI - On protecting whistleblowers. The NHS needs a staff support commission. PMID- 25134205 TI - Stevens will draw the poison from NHS leadership. PMID- 25134206 TI - Electronic records are vital. PMID- 25134207 TI - Older people's services. Japan's vision of a 'total care' future looks bright. PMID- 25134208 TI - Essay competition. Emerging leaders put pen to paper. PMID- 25134209 TI - Training. Fuel the fire of new leaders' ambitions. PMID- 25134210 TI - Hobby Lobby ruling may spur shift away from employer coverage. PMID- 25134211 TI - Justices side with health workers who object to paying union fees. PMID- 25134212 TI - Earnings outlook good for publicly traded hospital companies. PMID- 25134213 TI - McDonald faces steep learning curve in running troubled VA, insiders say. PMID- 25134214 TI - Wave of consolidation rumbles toward academic medical centers. PMID- 25134215 TI - New facility design aims for greater safety, efficiency. PMID- 25134216 TI - Where history happened: hospital treated Kennedy. PMID- 25134217 TI - Benefits unclear as states rush into Medicaid managed care. PMID- 25134218 TI - Hobby Lobby's blow to employer-based health insurance. PMID- 25134219 TI - Building consensus on what really counts. PMID- 25134220 TI - Advancing a medical home for surgical services. PMID- 25134221 TI - Targeting the right patients for support. PMID- 25134222 TI - Timing, earlier setbacks helped Obamacare pass: Jennings. PMID- 25134223 TI - What your nurse needs to know about genetics. PMID- 25134224 TI - Transition of pediatric patients to adult care: an analysis of provider perceptions across discipline and role. AB - The importance of successfully transitioning pediatric patients to adult care is increasingly recognized as more children with chronic diseases are living to adulthood. The aim of this study was to investigate the current state of provider perceptions across disciplines regarding transition of pediatric patients to adult care. Focus groups made up of providers of various roles and experience levels were conducted. A total of six major themes were identified. We conclude that pediatric providers share common concerns about transitioning pediatric patients to adult care. We reinforce many of the issues raised in the literature and also discuss a sense of professional ego that was identified as a barrier to successful transition, which is not widely reported in other studies. PMID- 25134225 TI - Newborn morbidities and health charges: the first eight weeks. AB - Recent health care legislative acts, federal budget cuts, and changes in health care reimbursement are posing significant challenges for mothers accessing health care for their infants. There is very little reported literature on post-birth newborn morbidity and associated charges for full-term infants within the first two months of life, a time of increased risk for mortality. PURPOSE: To examine infant morbidities, associated health care charges, and access to health care within the first eight weeks in healthy, full-term infants born to low-income, first-time mothers. DESIGN: A secondary analysis of data from a randomized clinical trial that compared infants' health and newborn health care charges. METHODS: Data on infant morbidity and health care charges on 139 first-time mothers and their healthy full-term newborns were collected at one and two months post-hospital discharge. Data were analyzed using descriptive statistics and two sample t-tests. FINDINGS: The most common infant morbidity was upper respiratory illness. Morbidities occurred as early as day two post-hospital discharge. Total charges were emergency room visits--$24,255, urgent care visits--$2,937, and rehospitalizations--$56,377. Most newborns received a well-baby clinic visit within 48 to 72 hours post-hospital discharge. CONCLUSION: Studies of morbidities, health care charges, and access to care for infants two months and less are very limited. However, such data are important because of increasing health care costs, health care budget cuts, and the lack of an infant morbidity surveillance system. PMID- 25134226 TI - Inpatient falls in freestanding children's hospitals. AB - Patient falls are considered a significant safety risk, but little evidence regarding the significance of falls in children is available. A multisite, observational study of fall events occurring in pediatric inpatients (younger than 18 years of age) from Child Health Corporation of America member hospitals was conducted to determine the prevalence and significance of falls. Fall prevalence was 0.84 per 1,000 patient days with 48% classified as preventable. Injuries occurred in 32%, but only two falls resulted in an increased length of stay; none resulted in permanent disability or death. Only 47% of the children who fell were identified to be at risk for fall. Alert mechanisms were used in 60% and preventive measures in 23%. These findings suggest that while inpatient pediatric fall rates are lower than those of adults, greater diligence in identification and risk reduction may further reduce the prevalence of falls and the proportion of fall-related injuries. PMID- 25134227 TI - 'Everyone knows' vs. finding the data. PMID- 25134228 TI - Clinical relevance of the Humpty Dumpty Falls Scale in a pediatric specialty hospital. AB - The Joint Commission requires pediatric hospitals to implement fall prevention programs and evaluate the efficacy of such programs. The Humpty Dumpty Falls Scale (HDFS), a seven-item assessment scale used to document age, gender, diagnosis, cognitive impairments, environmental factors, response to surgery/sedation, and medication usage, is one of several instruments developed to assess fall risk in pediatric patients. To determine the specificity and sensitivity of the HDFS in predicting falls in children hospitalized for pediatric specialty care, a team at a pediatric specialty hospital conducted a nonexperimental retrospective study that used a matched case-control design and chart review analysis. The discoveries suggest that the HDFS lacks accuracy in pediatric specialty patients. Using the HDFS cut-off score of 12 and above to indicate a high risk for falls in these children yields a high false-positive rate. Investigators and staff at pediatric specialty hospitals need to continue their pursuit of valid instruments and tools that contribute to fall reduction. PMID- 25134229 TI - Validation: a family-centered communication skill. AB - Family-centered care can seem challenging when family member behavior, choices, attitudes, or emotions are "difficult" or "challenging" to deal with. Yet nurses can develop skills to effectively interact with families in a wide variety of circumstances and then become able to practice family-centered care in any situation that might arise. One particularly useful skill is "validation," which means accepting what the family member says or does as a valid expression of thoughts and feelings in that particular circumstance at that particular time. Validation does not mean there is agreement or acceptance of unsafe behaviors, only that the nurse acknowledges that the family member's concerns and feelings are important and should be listened to and taken seriously, even in the presence of disagreement. Validation, which should be individualized, can take many forms, ranging from providing complete attention to reflection of statements, identification of possible unexpressed emotions, normalization, and finally, a full and genuine sense of connection. Understanding and practicing validation can empower nurses and family members, as well as support effective family-centered communication and problem solving, even in challenging circumstances. PMID- 25134230 TI - Promoting positive pediatric experiences for nursing students at the Children's Hospital of Pittsburgh of UPMC. AB - Challenges in professional nursing education today can be astonishing. Cognizant of the commitment to provide the most valuable learning experiences for our future nurses, academia and service organizations strive to meet this challenge. The escalation in nursing school enrollment, along with the increase in patient acuity and ongoing health care changes, requires hospitals and schools to continually review their practices to ensure positive outcomes. Providing pediatric nursing experiences to over 1,300 students annually, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center (UPMC) implemented a process to meet this need. A Faculty Advisory Council was established to provide a venue for representative nursing instructors to meet with the Nursing Education Department at the hospital. The commonality of focus by nursing faculty and Children's Hospital continues to strengthen both academia and service. This well-defined process supports positive pediatric experiences for nursing students at Children's Hospital of Pittsburgh of UPCM. PMID- 25134231 TI - Mitochondrial disease in children and adolescents. PMID- 25134232 TI - Message from the president. PMID- 25134233 TI - Right-sizing care: promoting sensitivity to a growing population. PMID- 25134234 TI - A job to serve others. PMID- 25134236 TI - 'All of a sudden, there was fire'. PMID- 25134235 TI - Building and sustaining a caring-based nurse-managed center. PMID- 25134237 TI - Investments counteract low margins. PMID- 25134238 TI - Devicemaker consolidation likely to continue. PMID- 25134239 TI - 'It's not pretty': could UPMC, Highmark feud be an omen for markets entering consolidation? PMID- 25134240 TI - Small-business exchanges off to rocky start. PMID- 25134241 TI - Preventing readmissions: is there an app for that? PMID- 25134242 TI - Data collection could stump next phase of predictive analytics. PMID- 25134243 TI - Wachter, McClellan offer takes on measuring quality. PMID- 25134244 TI - Better rules needed to boost use of big data. PMID- 25134245 TI - In ACO era, physicians will still play a leading--but changing--role. PMID- 25134246 TI - Make hospital visiting hours 24/7. PMID- 25134247 TI - CHI seeks integration in all directions, including insurance. PMID- 25134248 TI - "Docile bodies" or "impudent" women: conflicts between nurses and their employers, in England, 1880-1914. PMID- 25134249 TI - Conflicting chains of command in Dutch Catholic nursing (1839-1966). PMID- 25134250 TI - Fighting for one's own health--care as a cause of illness. PMID- 25134251 TI - [The day-to-day routine in hospitals--standards and conflicts, based on the example of the Rothschild spital in Vienna around the year 1900]. AB - The juxtaposition of official regulations and letters of complaint from Vienna's Rothschild Hospital shows, beyond the rhetoric and euphemisms of hospital reports, how lively and diverse day-to-day life was in a Jewish hospital around the year 1900. The letters of complaint query the official hospital rules and show that ideal and reality did not always coincide. Often, religious questions were at the root of the critique--such as doubts as to whether kosher dietary laws were adhered to--or conflicts between the agents involved, be they individuals or groups, patients, nurses, physicians or administrative staff. As part of this process, power structures, social hierarchies, patient rights and gender issues were called into question and renegotiated. PMID- 25134252 TI - [Parish nursing around the year 1900]. AB - This contribution first introduces the factors that supported the development of parish nursing before going on to explain the diverse organizational concepts involved and their development over time. It looks at the various Catholic and Protestant as well as secular institutions active in this field. The article then discusses the manifold tasks, fields of work and approaches to problem-solving that were characteristic of parish nursing. The various cultural, social and religious problems that the parish nurses had to contend with on a daily basis are also presented, including the increasing competition with other professional groups. The article concludes by looking at the standing of parish nurses in society and the advantages and disadvantages of parish nursing as opposed to hospital nursing from the point of view of the parish nurses themselves. PMID- 25134253 TI - ["Practical tuberculosis care outside the hospital stands and falls with the tuberculosis nurse". Challenges in out-patient care, using the example of tuberculosis nurses in the first third of the 20th century]. AB - Once it had become apparent that tuberculosis sanatoriums were unable to stop this widespread disease, out-patient tuberculosis clinics were established for patients and their relatives in the German Reich. These clinics, which started in the late nineteenth century, employed physicians and tuberculosis nurses. The nurses were generally community or parish nurses, specialized carers not being trained until later. On the one hand, their tasks included the work at these clinics, where they assisted the physician, admitted patients and carried out x rays and lab tests. On the other hand--and this was their main task--they visited the sick and their families at home, informed them about tuberculosis, instructed them on questions of hygiene and the appropriate behaviour and made sure these instructions were adhered to. If they were able to offer material help as well, they were received more willingly--and they could only make their visits with a patient's consent. Due to the lack of tuberculosis medicines, the work of the tuberculosis nurses was a mainstay in the fight against this highly infectious disease. They often had to overcome the resistance of general practitioners and also of some patients and their families. But they loved doing their job because they were appreciated by the tuberculosis doctors, had a relatively high degree of freedom, authority and responsibility as health visitors and achieved visible results through personal commitment. PMID- 25134254 TI - ["They are enjoying their first holiday ever"--working with the elderly, from the post-war years up to the early 1970s]. AB - While, in the post-war years and into the 1950s, the building of old people's and care homes and the allocation of home places in those homes was seen as the main task of municipal care institutions for the elderly in Frankfurt am Main, in the decade that followed their main task shifted towards increasing the possibilities of providing care in people's own homes, delaying the move into old people's homes and breaking through the loneliness that elderly people were presumed to experience. Supported by the state, community housing was provided with flats for elderly people and with carers to look after their needs. The "warm rooms" of the post-war period changed into clubs, where members met and received guidance. In the late 1960s the clubs were extended into day-care centres, offering a range of consultation services, organized day trips and recreational holidays for the elderly. It was hoped that "meals-on-wheels" in combination with age-appropriate living conditions would delay the move into a home. But these plans were not adequately developed in the 1960s and often it was not clear who would pay the bills. The same was true of outpatient medical care which had traditionally been the task of community nurses, but was now increasingly carried out by local authority carers, who also provided household assistance. This kind of care could only ever be given for a limited period of time and, while it was able to delay the move into an old people's home, it could not replace it. PMID- 25134255 TI - [The "secret book" of Dr Friedrich Benjamin Osiander: anonymous births in the Gottingen Accouchierhaus, 1794-1819]. AB - The problem of anonymous or confidential deliveries, a subject of current controversy, has a long history. Some maternity hospitals offered the possibility for "clandestine" births as early as the 18th and 19th century. A recently emerged source about the maternity clinic of Gottingen University allows insight into the motives that led to keeping a birth secret and the consequences of such a clandestine birth for mother, father and child. The director of the institution, a professor of obstetrics, wrote case reports on the women, who paid a handsome sum for his help and the in-patient care they received. In return, these women could be admitted under a pseudonym, and thus falsify their child's birth certificate; moreover they were not used as teaching material for medical students and midwife apprentices, whereas "regular" patients had to give their names and, in return for being treated free of charge, be available for teaching purposes. The ten cases that have been painstakingly investigated reveal that the reasons that led the women and men to opt for an anonymous birth were manifold, that they used this offer in different ways and with different consequences. All of these pregnancies were illegitimate, of course. In one case the expectant mother was married. In several cases it would be the father who was married. Most of the women who gave birth secretly seem to have given the professor their actual details and he kept quiet about them--with the exception of one case where he revealed the contents of the case report many years later in an alimony suit. Only one of the men admitted paternity openly, but many revealed their identity implicitly by registering the pregnant woman or by accompanying her to the clinic. If the birth was to be kept secret the child needed to be handed over to foster parents. By paying a lump sum that covered the usual fourteen years of parenting, one mother was able to avoid any later contact with her son. In most cases contact seems to have been limited to the payment of this boarding money. One of the couples married later and took in the twins that had been born clandestinely out of wedlock. One mother kept close contact with her son through intermediaries. All of the women who gave birth in this clandestine fashion received practical as well as financial support, often from the child's father or from a relative. Few of them came by themselves. In those days, only women who used the maternity hospital free of charge would have been as isolated in the difficult perinatal period as are women today who choose to deliver their babies anonymously. PMID- 25134256 TI - [A ''humanitarian duty and a matter of honour for German Jewry": "feeble-minded" Jewish children and the Institution in Beelitz]. AB - In 1908, in collaboration with the Bnei Briss, the German Association of Israelite Communities founded an institution for intellectually disabled Jewish children in Beelitz with the aim of educating 7-14-year-olds, using therapeutic pedagogy. The institution was part of the philanthropic efforts undertaken by German Jewry in that period. It was set up in the wake of the German Kaiser's call to found more philanthropic institutions, and its establishment is indicative of the efforts at integration being made by German Jewry. In their fund-raising material, the German Association of Israelite Communities stressed the "loyalty and patriotism" of German Jewry and described the establishment of the institution as "a humanitarian duty" and "a matter of honour for German Jewry". It was, therefore, demands from the non-Jewish world that led to the foundation of a Jewish institution; however, its establishment was also symbolic of the struggle against anti-Semitism and indicative both of German Jewry's dissimilation and their efforts at integration. The article investigates the struggle of Jewish parents to have their children admitted to the institution, the philosophy and teaching methods of the director Sally Bein (1881-1942) and his wife Friederike Rebeka Bein (1883-1942), the background of the students, the causes of intellectual disability, as well as the disagreements that occurred between parents, teachers and the director. The article also discusses the successes and failures of therapeutic pedagogy. PMID- 25134257 TI - [Deaf Jews in Germany, 1800-1933. A look at the history of a dual minority]. AB - This study examines the importance of religious denomination in the German community of deaf people in the 19th century and up until 1933, focusing on the dual minority status of deaf Jews. It shows that the educational system for the deaf and the deaf movement as such were, in structure and content, informed by the Christian, primarily the Protestant, faith. This meant that deaf Jewish people were in danger of facing a conflict between their identity as Jews and their identity as deaf people. In order to resolve this dilemma, Jewish philanthropists and deaf people created a range of complementary structures: schools where deaf Jewish children received tuition tailored to their needs, religious services in sign language and a Jewish deaf association for mutual support and companionship. But being members of two stigmatized and marginalized groups made the Jewish deaf vulnerable from several sides. The discursive association of deafness, Judaism and heredity played a particular part in this. This study comes to the conclusion that deaf Jews did not want to choose between their deaf and Jewish identities but they wanted to belong to both. As a result they suffered from the negative views that some deaf people had of Jews and some Jews of deaf people--as well as from the double discrimination by the mainstream society. PMID- 25134258 TI - [The flu epidemic after World War I and homeopathy--an international comparison]. AB - The "Spanish Flu" began in 1918 and was the most devastating pandemic in human history that had ever been, claiming more lives than World War I. The flu virus had not yet been discovered, and the usual therapy measures were merely symptomatic. In many parts of the world the pandemic was treated by homeopaths. At the time, homeopathic medical practices, out-patient clinics and hospitals existed in various countries. To this day homeopaths refer to the successful homeopathic treatment of the "Spanish Flu". The following paper looks at what this treatment consisted in and whether it was based on a particular concept. It also examines contemporary evaluations and figures, as well as the question as to whether homeopathy experienced a rise in demand as a consequence of its success during the pandemic. PMID- 25134259 TI - Rethinking leadership development. PMID- 25134260 TI - The surgery panel in Diego Rivera's Detroit Industry Murals. PMID- 25134261 TI - Vital amines, purple smoke. A select history of vitamins and minerals. PMID- 25134263 TI - The mysterious illness of Emma Lazarus, Lady Liberty's poet. PMID- 25134262 TI - An obstetric story. PMID- 25134264 TI - The most memorable patient I never saw. PMID- 25134265 TI - Fall from grace. PMID- 25134266 TI - Dr. Marr responds to Dr. Volpintesta. PMID- 25134267 TI - Fall from grace. PMID- 25134268 TI - Fall from grace. PMID- 25134269 TI - Dr. Marr responds to Dr. Sprecace and Dr. Spaeth. PMID- 25134270 TI - Experts: know your patients' benefits and work to conserve them. AB - Case managers should know their patients' insurance benefits and out-of-pocket expenses when they develop a discharge plan to make sure the patient can afford the plan they are putting in place. Take policy limitations into account and preserve benefits for their future needs. Look for community resources such as medication assistance plans and clinics that charge a sliding scale when patients don't have coverage for needed services. Make sure patients and family members understand the benefits when they make choices about post-acute care. PMID- 25134271 TI - Being creative when benefits are maxed out. PMID- 25134272 TI - Knowing benefits helps patients make choices. PMID- 25134273 TI - Audits highlight need for documentation. AB - The Centers for Medicare & Medicaid Services' "Probe and Educate" initiative to determine hospitals'compliance with the two-midnight rule makes it clear that case managers must review physician documentation as well as medical necessity. The Medicare Administrative Contractors are focusing on short stays when physician documentation doesn't support the expectation of a two-midnight stay. They're looking at flawed admission orders, and when the orders to admit are issued by a practitioner who does not have admitting privileges at the hospital. Another area of focus is physician statements without documentation of the reason for the need for inpatient treatment. PMID- 25134274 TI - Visual cues keep treatment team alert. AB - At Good Samaritan Medical Center in West Palm Beach, FL, a throughput initiative that uses colored magnets to indicate anticipated discharges has cut emergency department holding time and increased the number of discharges by 2 p.m. The charge nurse, case manager, and discharge planner meet daily, make their best clinical guess about the patient's discharge and place a red, yellow, or green magnet on a white board at the nurses station. When team members pass the board, they are alerted to anticipated discharges and know to make patients with a green magnet a priority. The case managers and nurses write the expected discharge on a white board in the patient rooms and initiate a discussion with patients and family members to prepare them for discharge. PMID- 25134276 TI - Heart failure program cuts readmission rate. PMID- 25134275 TI - Case management insider. Family caregivers: a key component of the discharge planning process. AB - The role of the family caregiver may not be for a short time period. It could go on for months or even years. As case managers, our role is to ensure that we have provided our family caregivers with all the information that they may need to care for their loved one at home or in another care setting. This will take some time, but it is time well spent and will reduce the likelihood that an unnecessary trip to the emergency room will take place. Remind caregivers to know their strengths, limitations and to always be flexible! PMID- 25134277 TI - Decreasing preventable readmissions? AB - Bioethicists can advocate for improved communication with family caregivers when a patient is going to be discharged from the hospital. Healthcare providers are often unaware of a family member's inability to provide needed care. Many patients who access "safety-net" public hospitals have worse outcomes of hospitalization, including readmissions. Bioethicists can advocate for more partnerships between hospitals and community-based programs. PMID- 25134279 TI - Pregnancy outcome after laparoscopic myomectomy. AB - PURPOSE OF INVESTIGATION: Main purpose of this study was to analyze the reproductive and obstetrical outcome as delivery mode and incidence of major complications (uterine bleeding and uterine rupture) after laparoscopic myomectomy. MATERIALS AND METHODS: The authors conducted an observational study in patients who underwent laparoscopic myomectomy. Inclusion criteria were: surgery performed for single and or multiple myomas sized between five and 15 cm and pregnancy desire. Exclusion criteria were: surgery for pedunculated myomas and male or tubal infertility. Collected data on pregnancy desire, success in obtaining pregnancy surgical interval time before pregnancy, performing assisted reproductive medicine, gestational weeks, mode of delivery, indicating a possible cesarean section, and complications. On collected data the authors calculated pregnancy and abortion rates. RESULTS: Among patients aged between 19 and 42 years who answered a telephonic questionnaire, the authors selected 185 patients with pregnancy willing. A total number of 426 myomas were removed; 115 (62.2%) patients reported 151 pregnancies, nine in a total of 17 patients achieved it with reproductive assistance, 38 pregnancy ended in abortion, and two had an ectopic implantation. The authors finally reported 111 successful pregnancy, with seven preterm deliveries (6.3%). Mode of delivery had been cesarean section in 69 cases (63.4%) and vaginal delivery in 42 cases (36.6%), with a respective mean interval time between surgery and delivery of 24.6 +/- 20.0 months and 19.2 +/- 13.3 months. CONCLUSION: Laparoscopic myomectomy proved to be an effective procedure feasible for women who wish to become pregnant with a subsequent good reproductive outcomes, both in terms of pregnancy and abortion rates that were comparable with the literature. If laparoscopic suturing of the fovea myometralis is adequate, there are no contraindications for vaginal delivery, regardless of the patient's age, the number, size, and location of the myomas removed. PMID- 25134278 TI - Serum markers of oxidative stress and endometriosis. AB - PURPOSE OF INVESTIGATION: To assess the changes secondary to chronic inflammation in women with and without pelvic endometriosis by the determination of serum thiols and carbonyls. MATERIALS AND METHODS: Sixty-seven women with endometriosis consecutively submitted to laparoscopy and 41 women without endometriosis consecutively submitted to tubal ligation (control group) were selected. Serum levels of total thiols and carbonyls were determined in both groups. RESULTS: Patients with endometriosis had significantly lower thiol levels than controls (342.37 +/- 142.09 microM vs 559.60 +/- 294.05 microM) (p < 0.001), as well as significantly lower carbonyl levels (8.97 +/- 3.76 microM vs 16.40 +/- 9.26 microM) (p < 0.001). Other clinical characteristics were not associated with changes in marker levels. The cutoff point established by the ROC curve was 396.44 microM for the thiols, with 73.1% sensitivity and 80.5% specificity, and 14.9 microM for the carbonyls, with 94% sensitivity and 51.2% specificity. CONCLUSIONS: The serum thiol levels revealed an increase in oxidative stress related to the development of pelvic endometriosis. PMID- 25134280 TI - Predictive value of fetal fibronectin on the embryonic loss of patients with recurrent spontaneous abortion in early pregnancy. AB - OBJECTIVE: This work aims to investigate the predictive value of fetal fibronectin (fFN) in embryonic loss of patients with recurrent spontaneous abortion (RSA) in early pregnancy. MATERIALS AND METHODS: Eighty-four patients with RSA in early pregnancy were selected as the test group and 31 healthy women in early pregnancy were selected as the control group. The ages and number of previous abortions, along with other information, were recorded. These patients underwent a fFN test, and their pregnancy outcome was followed up until 14 weeks. RESULTS: The incidence of spontaneous abortion was 20.24% in the test group and 9.68% in the control group. The positive fFN [fFN (+)] rate was 57.14% in the test group and 12.90% in the control group, indicating a statistically significant difference (p < 0.01, chi2 = 17.89). The incidence of spontaneous abortion was 29.17% (14/48) in the fFN (+) group and 8.33% (3/36) in the fFN (-) group, indicating a statistically significant difference (p < 0.05, chi2 = 5.53). The sensitivity, specificity, and positive and negative predictive values in the prediction of abortion in fFN (+) patients of the test group were 82.35%, 49.25%, 29.17%, and 91.67%, respectively. CONCLUSION: If detected at an early stage of pregnancy, fFN in patients with RSA is largely related to the prediction of abortion and facilitates the evaluation of pregnancy outcomes. PMID- 25134281 TI - Microdose flare-up vs. flexible-multidose GnRH antagonist protocols for poor responder patients who underwent ICSI. AB - PURPOSE: To compare the performance of microdose flare-up (MF) and flexible multidose gonadotropin-releasing hormone (GnRH) antagonist protocols in poor responder patients who underwent intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: One hundred and 12 consecutive patients (217 cycles) suspected to have poor ovarian response were enrolled. Group 1 (MF GnRH agonist group) constituted 64 patients (135 cycles) who underwent MF GnRH agonist protocol. Group 2 (flexible-multidose GnRH antagonist group) constituted 48 patients (82 cycles) who underwent flexible-multidose GnRH antagonist protocol. RESULTS: The duration of stimulation (d) (11.5 +/- 2.1 vs. 10.4 +/- 2.7, p < 0.01) and the total dose of gonadotropin used (IU) (5,892.9 +/- 1,725.7 vs. 4,367.5 +/- 1,582.1, p < 0.05) were significantly lower in Group 2 when compared to Group 1. The numbers of retrieved oocyte-cumulus complexes (4.5 +/- 3.6 vs. 5.9 +/- 4.9, p < 0.05), metaphase II oocytes (3.6 +/- 3.1 vs. 4.9 +/- 4.2, p < 0.05), two pronucleated oocytes (2.6 +/- 2.3 vs. 4.0 +/- 3.4, p < 0.05), the number of available embryos at day 3 (2.6 +/- 2.2 vs. 4.2 +/- 3.2, p < 0.05) and the rate of embryos with > or = seven blastomeres and < 10% fragmentation at day 3 (35.9% vs. 65.1%, p < 0.05) were significantly lower in Group 1 when compared to Group 2. The number of embryos transferred (2.2 +/- 1.3 vs. 2.4 +/- 0.9), the clinical pregnancy per embryo transfer (16.3% vs. 25.8%), and the implantation rate (8.6% vs. 12.2%) were comparable between groups. CONCLUSIONS: Although the flexible-multidose GnRH antagonist protocol produced better oocyte and embryo parameters, the clinical pregnancy rate and the implantation rates were comparable between the flexible-multidose GnRH antagonist and MF protocols in poor responder patients. PMID- 25134282 TI - Computerized in vivo classification of methylene blue stained fallopian tube mucosal damage: preliminary results. AB - OBJECTIVE: Fertiloscopy is a simple minimal invasive method which allows salpingoscopy and microsalpingoscopy in order to examine the mucosa of the fallopian tubes of patients with unexplained infertility. Infectious tubal damage is a common cause of tubal infertility. In 1998 it was demonstrated that nuclear staining of cellular nuclei during microsalpingoscopy with methylene blue provides a simple in vivo method to evaluate cellular damage of the tubal epithelium. The purpose of this study was to introduce and statistically test a new computerized method to objectively evaluate the extent of tubal damage. DESIGN OF RETROSPECTIVE STUDY: Cooperation of two Departments of Gynecology and Obstetrics (Krankenanstalt Rudolfstiftung, Vienna, Austria and CRES Center, Hopital Natecia, Lyon, France) with the University of Art and Design, Linz, Austria and University Hospital, Vienna, Austria. MATERIALS AND METHODS: Microsalpingoscopic images from ten female patients, aged between 18 and 45 years with primary infertility, showing stained nuclei in damaged intrafallopian tubal epithelium were provided by Antoine Watrelot, CRES Center, Hopital Natecia, Lyon, France. These images were evaluated by an experienced medical expert staff examiner and a computerized standard method called cross-correlation and template matching. The obtained numbers of nuclear stainings were statistically evaluated. RESULTS: Computerized evaluation of nuclear staining of damaged intrafallopian epithelial cells in female patients with infertility obtains similar but more reproducible results compared to manual evaluation (p = 0.007). CONCLUSION: Normalized cross-correlation can be used to measure tubal damage diagnosed by in vivo methylene blue dyeing during microsalpingoscopy and might facilitate the decision for in vitro fertilisation in patients with unclear unexplained infertility in further studies. PMID- 25134283 TI - Study of urotensin II gene and serum levels in relation to pre-eclampsia. AB - OBJECTIVE: To verify the relationship between Urotensin II (UII) gene and serum levels and pre-eclampsia (PE). STUDY DESIGN: Prospective case control study. SETTING: Tertiary Obstetric centre and university hospital. SUBJECTS: A total of 80 pregnant women at their third trimester were included, 30 of which were with mild PE, 30 with severe disease and 20 age- and BMI-matched normotensive pregnant women (controls). MATERIALS AND METHODS: UII gene polymorphism as well as UII serum levels were assessed and compared in patients vs. control. RESULTS: No difference was seen between the groups in terms of age or parity at the time of recruitment. A statistically significant difference in the Urotensin II genotype frequencies between patients and control groups was found. The mean serum UII, also showed a significant difference between the studied groups, and control group. Comparing the observed and expected values of UII genotype frequencies in mild, severe PE, and in controls, no significant difference was noted in the homo mutant, the hetero-mutant or the wild genotypes. CONCLUSIONS: Elevation of UII in the serum of PE patients could be correlated to the severity and/or progression of the disease. The UII genotype frequencies between patients and control groups showed a significant difference, which implies a potential benefit for UII gene or level in serum as a diagnostic or prognostic indicator in pre-eclampsia. PMID- 25134284 TI - Effect of gestational weight gain as well as rehabilitation training on postnatal pelvic muscle strength. AB - OBJECTIVE: The current study explored the impact of gestational weight gain on postnatal pelvic muscle strength and the effect of low-frequency electrical stimulation combined with biofeedback training on strength recovery. MATERIALS AND METHODS: A total of 126 mothers six to eight weeks after term delivery were recruited at Peking University Shenzhen Hospital from August 2010 to July 2011. According to gestational weight gain, they were divided into two groups: the < 15 kg (A) and > or = 15 kg (B) groups. Pelvic floor muscle fibre strength was determined. Target low-frequency electrical stimulation combined with biofeedback training was conducted. After training, pelvic floor muscle fiber strength was determined again for effect evaluation. RESULTS: Before training, types I and II pelvic floor muscle fiber strength of group B was noticeably lower than that of group A (p < 0.05). After rehabilitation, the pelvic floor muscle strength of both groups significantly increased (p < 0.05). However, types I and II pelvic floor muscle fiber strength of group B was still significantly lower than that of group A (p < 0.05). CONCLUSION: Gestational weight gain negatively influences pelvic floor muscles. Low-frequency electrical stimulation combined with biofeedback training improves postnatal pelvic floor muscle fiber strength. A less gestational weight increase indicates faster postnatal pelvic muscle strength recovery and a better rehabilitative effect. PMID- 25134285 TI - Sublingual misoprostol is better for cervical ripening prior to hysteroscopy in post-menopausal women. AB - BACKGROUND: The aim of the present study was to evaluate the efficacy of misoprostol administered sublingually, vaginally or rectally on cervical ripening before hysterescopic surgery in post-menopausal women. MATERIALS AND METHODS: Post-menopausal women were randomised to receive either 400 ug of misoprostol, administered sublingually, vaginally or rectally six hours and 12 hours prior to operative hysterescopy. RESULTS: Patients were randomized to receive receive sublingual (n = 30), rectal (n = 30) or vaginal (n = 30) misoprostol. The control group did not receive misoprostol (n = 30). The four groups were comparable in terms of preoperative cervical width after misoprostol administration. The mean cervical widths for control group was 9.0 +/- 1.1 mm and the mean post-treatment cervical widths for the sublingual, vaginal, and rectal groups were 7.1 +/- 1.1 mm, 8.9 +/- 1.3 mm, and 8.6 +/- 1.5 mm, respectively. The cervical widths of sublingual group were significantly different from control, vaginal; and rectal groups (p < 0.001). CONCLUSION: Four hundred micrograms of sublingual misoprostol, 12 and six hours prior to operative hysteroscopy has a significant cervical ripening effect compared with vaginal, rectal, and control groups in post-menopausal women. PMID- 25134286 TI - Thermal balloon ablation versus transcervical endometrial resection: evaluation of postoperative pelvic pain in women treated for dysfunctional uterine bleeding. AB - PURPOSE OF THE STUDY: To evaluate postoperative pain after mini-invasive surgical treatment for dysfunctional uterine bleeding (DUB) with transcervical endometrial resection or thermal ablation balloon. MATERIALS AND METHODS: A longitudinal observational study, analyzing 47 women affected by DUB who underwent endometrial ablation was conducted. The authors collected evaluation of pelvic pain at one and four hours after intervention and the individual necessity of analgesics. After 30 days, all patients underwent a gynecological visit to evaluate postoperative outcome. RESULTS: Pelvic pain was higher one and four hours after procedure in thermal balloon ablation group, and patients in the same group required more analgesic rescue dose. There were no complications such as uterine perforation, heavy blood loss or thermal injuries with both the procedures. CONCLUSION: Thermal balloon ablation appears a more painful procedure than endometrial resection, both in the immediate postsurgical time and 30 days after surgery. Ad hoc anaesthesiologic and analgesic protocol should be adopted to ensure quick recovery and good acceptance of the procedure. PMID- 25134287 TI - Is there any association between mild hypertension and hot flash experience among women? AB - OBJECTIVE: To determine the association between ambulatory blood pressure (ABP), heart rate, and hot flash (HF) experience among women. MATERIALS AND METHODS: The authors recruited 110 women aged 22 to 65 years with mild essential hypertension or normotension confirmed by 24-hour ABP monitoring. None of the women had organ damage, inflammatory diseases, on estrogen replacement therapy or any other risk factors. Participants wore an ABP monitor that both records heart rate during 24 hours and noted their awake and sleep times. HF were assessed using an everyday complaint questionnaire that included symptoms associated with menopause. Each participant was asked whether or not she had experienced each symptom during the two weeks before the interview. RESULTS: Fifty-five of the participants (45%) reported having had HF during the two weeks before they completed the questionnaire. The results show that the prevalence of essential hypertension (EH) in the group of women who had HF was significantly higher than the group of women that did not have HF (p = 0.035). The authors also found that hypertensive women had HF more often than normotensive women (p = 0.035), but other parameters including mean awake and sleep systolic BP values, mean awake and sleep diastolic BP values, heart rates, and nocturnal dipping of BP did not differ statistically among the group of women who had HF and the group of women who did not have HF (p > 0.05). CONCLUSIONS: These data suggest that the prevalence of EH in the group of women who have HF is significantly higher than the group of women that does not have HF. PMID- 25134288 TI - High rates of abnormalities in hysterosalpingography in couples with male factor infertility. AB - The rate of anatomical abnormalities in infertile couples with obvious male factor is unknown. For this purpose the authors retrospectively analyzed 376 hysterosalpingographies (HSG) of couples with severe male factor. Patients were subdivided into four groups according to the woman's age, and primary or secondary infertility: A--less than 35-years-old, primary infertility, B--less than 35-years-old, secondary infertility, C--35-years-old or more, primary infertility, and D--35-years-old or more, secondary infertility. Overall, abnormalities in HSG were demonstrated in 25.5% of the patients, and in 18, 21, 52, and 40 percent of patients in groups A, B, C and D, respectively. Age was found to be a significant independent risk factor (p < 0.05) while primary or secondary infertility was not. The adjusted odds ratio for woman who were 35 years-old or more to have any abnormalities in HSG were 3.7-fold greater (95% CI 2.2- 6.23), than women who were less than 35-years-old. In conclusion, relatively high rates of female mechanical abnormalities may be found even in infertile couples with obvious male factor and are significantly more prevalent in older women. PMID- 25134289 TI - Frozen section of uterine curetting in excluding the possibility of ectopic pregnancy--a clinicopathologic study of 715 cases. AB - INTRODUCTION: To investigate the utility of frozen section of uterine curetting in excluding the possibility of ectopic pregnancy (EP). MATERIALS AND METHODS: A retrospective analysis of 715 curetting records in the present hospital from July 1999 to May 2009 was obtained. All specimens were processed routinely with frozen section and paraffin section. RESULTS: Of 715 cases, frozen section analyses were discordant in 33 cases (4.6%), including 32 cases under-diagnosed, and one case over-diagnosed, compared with the final diagnoses. Frozen section had a sensitivity of 92.6%, specificity of 99.6%, and frozen section accuracy rate of 95.4%. CONCLUSIONS: Frozen section is a useful and rapid method to differentiate EP from intrauterine pregnancy. PMID- 25134290 TI - Increased platelet count in severe peritoneal endometriosis. AB - OBJECTIVE: Platelet count (PC) is higher in chronic inflammatory diseases. The aim of this study was to evaluate the PC in patients with severe pelvic endometriosis. MATERIALS AND METHODS: Patients with advanced stage pelvic endometriosis were retrospectively evaluated in a tertiary center between January 2009 and December 2011. Patients with pelvic endometriosis were divided into two groups; advanced stage peritoneal endometriosis were classified as Group 1 (n = 28). Group 2 consisted of 29 patients which had ovarian endometrioma without clinically apparent peritoneal endometriosis foci. Group 3 included 51 women as control subjects. PC between the groups was tested by Student's t test. The mean values of three groups were analyzed by using one way ANOVA test followed post hoc test Bonferroni. RESULTS: PC in patients with pelvic endometriosis were found to be higher from the control group (290 +/- 67 10(9)/1; 264 +/- 63 10(9)/1, respectively; p = 0.038). Patients with peritoneal endometriosis (Group 1) had significantly higher PCs compared with the healthy controls (309 +/- 65 10(9)/1; 264 +/- 63 10(9)/1; respectively; p = 0.011). CONCLUSION: Increased PC in advanced stage pelvic endometriosis may be a sign of increased systemic inflammation. The systemic inflammation may be more apparent in advanced stage peritoneal endometriosis. PMID- 25134291 TI - Risk of recurrent menorrhagia after hydrothermoablation: role of GnRH analogues neoadjuvant treatment in long-term successful rate. AB - OBJECTIVE: To evaluate the long-term effectiveness of presurgical therapy with GnRH analogues in patients who underwenthydrothermal endometrial ablation (HTA) for menorrhagia and assess the relationship between sonographically measured myometrium thickness and pelvic pain. MATERIALS AND METHODS: A prospective randomized control study comparing 15 women (Group A) with presurgical subcutaneous triptorelin depot injection before HTA with controls (Group B, n = 15). Inclusion criteria were: recurrent menorrhagia, uterus length < 12 cm, no previous hormonal therapy for at least six month, and family plan completed. Student's t test was applied, as appropriate, to compare continuous variables. Proportion were compared with chi-squared. RESULTS: After 12 months of follow-up, Group A showed a significantly lower (0% vs 20%; p = 0.03) failure rate after hydrothermoablation than the Group B and a generally higher successful rate at 24 and 48 months. The discomfort, evaluated with VAS, showed a mean value of 47.6 +/ 15.9 +/- SD); 96.7% of women reported a mild-moderate postoperative pain. No perioperative and late complications were recorded. CONCLUSIONS: Presurgical treatment with GnRH analogues seems to improve long-term efficacy of HTA. Perioperative pelvic pain seems to not be affected by myometrium thickness. PMID- 25134292 TI - Serum levels of androgens and prostate-specific antigen in endometriosis. AB - OBJECTIVE: The aim of the present study was to evaluate the levels of serum androgens and prostate-specific antigen (PSA) levels in patients with endometriosis. MATERIALS AND METHODS: Patients with Stage III/IV (advanced stage) endometriosis were compared to controls with respect to basal serum levels of total testosterone (T), free testosterone (fT), androstenedion (A), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulphate (DHEA-S), and PSA in the early follicular phase of menstrual cycle for this prospective case control study. RESULTS: Level of T, fT, A, DHEA, and DHEA-S were higher in patients with endometriosis when compared to control subjects, but the difference was not statistically significant. The mean PSA level was 0.0074 +/- 0.0120 ng/ml in patients with endometriosis and 0.0059 +/- 0.0056 ng/ml in control group and there was no statistically significant difference between groups (p = 0.58). CONCLUSION: Serum basal androgens and PSA levels are higher in endometriosis group with respect to control but the differences are not statistically significant. PMID- 25134293 TI - Rising cesarean section rates, a patient's perspective: experience from a high birth rate country. AB - PURPOSE OF INVESTIGATION: To investigate the effect of social class, education and antenatal care on cesarian section (CS) rate and women's preference for CS. MATERIALS AND METHODS: This is a descriptive study performed on 509 women attending postnatal clinics in three primary care units in Ismailia governorate, Egypt. The study performed via a structured questionnaire including questions related to background socio-demographic data, questions related to obstetrical history for the last pregnancy and delivery, and questions related to economic standards. RESULTS: The study included 266 participants (52.3%) that delivered by CS in their last delivery. CS rate was significantly higher in highly educated women and high economic standard. Only 29 (7.7%) reported that they had preferred CS as a method of delivery. Educational level and economic standards significantly affected the proportion of women preferring CS as a method of delivery (p = 0.02 and p = 0.01, respectively). In a stepwise logistic regression model, significant factors affecting CS rate were: the method of delivery preferred (p < 0.005) and educational level (p < 0.05). CONCLUSION: Educational level and economic standards significantly affected women's preference towards CS and CS rate. PMID- 25134294 TI - Effectiveness of pericervical tourniquet by Foley catheter reducing blood loss at abdominal myomectomy. AB - OBJECTIVE: To evaluate effectivenes of pericervical tourniquet by Foley catheter reducing blood loss at abdominal myomectomy. MATERIALS AND METHODS: Retrospective chart review of 67 cases, with symptomatic myoma uteri and undertaken abdominal myomectomy, was performed. Myomectomy was performed in Group 1 (n = 34) by Foley catheter tourniquet around both uterin vessels and in Group 2 (n = 33) the tourniquet was not performed. RESULTS: The average blood loss during myomectomy was 286.4 +/- 137.5 ml for the tourniquet group and 673.8 +/- 172.3 ml for the control group. Postoperative blood transfusion was necessary in two patients from the control group. Technique significantly reduced the intraoperative blood loss and postoperative hemoglobin fall in patients. No serious complications occured on account of the tourniquet technique. CONCLUSIONS: The pericervical tourniquet by Foley catheter is a safe and effective method for reducing blood loss during abdominal myomectomy, although it should be evaluated in a randomized controlled trial. PMID- 25134295 TI - TVT-ABBREVO: efficacy and two years follow-up for the treatment of stress urinary incontinence. AB - PURPOSE: To assess the effectiveness of inside-out TVT-ABBREVO in the surgical treatment of female stress urinary incontinence (SUI) with mean two-year follow up. MATERIALS AND METHODS: Fifty-six women underwent surgery for moderate-severe SUI. The technology used was the TVT-ABBREVO inside-out. Each woman at 12 and 24 months underwent postoperative evaluation by means of urodynamics, Q-tip test, CST, transperineal ultrasonography, and administration of "King's Health Questionnaire" (KHQ). RESULTS: The mean age of the women was 57.03 +/- 11.1 years (range 42-75). Postoperative urodynamics (12 months follow-up) resulted to be normal in 43/56 patients (76.79%), in 10/56 (17.86%) cases resulted in a considerable improvement of the symptomatology, and only 1/56 (1.78%) case had de novo overactive bladder (OAB), in 2/56 (3.57%) symptomatology unchanged. After administration of the KHQ 43/56 cases (76.79%) had resolution of the symptomatology, 10/56 cases (17.86%) improvement of the symptomatology, and no change in 3/56 cases (5.36%). CONCLUSION: In the authors' experience, the TVT ABBREVO resulted technically simple. The TVT-ABBREVO procedure provides high objective and subjective long-term efficacy, a clinically meaningful improvement in patient quality of life, and an excellent safety profile. PMID- 25134296 TI - Is thrombin-activatable fibrinolysis inhibitor antigen (TAFIag) level significant in recurrent miscarriage? AB - OBJECTIVE: The aim of this study was to evaluate the plasma thrombin-tat fibrinolysis inhibitor antigen (TAFIag) levels in women with recurrent miscarriage (RM) and age-matched healthy parous women as controls. MATERIALS AND METHODS: A total of 80 patients were enrolled in this study. As a study group (group 1), the authors evaluated 49 RM patients who had two or more consecutive abortions with unknown etiology before 12 weeks of gestation. The remaining 31 patients (group 2) were age-matched healthy parous women with no history of miscarriage and experienced at least one live baby. RESULTS: Comparisons of blood TAFIag levels revealed no statistically significant difference between women with recurrent miscarriages and control group. CONCLUSIONS: The findings of the present study indicated that TAFIag level was not associated with recurrent miscarriages. PMID- 25134297 TI - Experience of hysteroscopy indications and complications in 5,474 cases. AB - OBJECTIVE: To evaluate the indications, intraoperative diagnoses, and complication rates of both diagnostic and operative hysteroscopic procedures. MATERIALS AND METHODS: Five thousand four hundred seventy-four (5474) hysteroscopic procedures performed in the department of gynecologic endoscopy unit between May 2005 and December 2012 were retrospectively analyzed from the archives. Indications, intraoperative diagnosis, and complications of all gynecological endoscopic procedures are recorded. RESULTS: Abnormal uterine bleeding in premenopausal and postmenopausal women was the most frequent indication for diagnostic hysteroscopies in 1,887 (40%) cases. The most common preoperative indication for operative hysteroscopy was endometrial polyps in 469 (55.7%) cases and submucous leiomyomas in 151 (17.9%) cases. In this series, the most common complication was uterine perforation which occured in 15 (0.27%) out of 5,474 cases and the rate for diagnostic hysteroscopy and operative hysteroscopy was 0.06% and 1%, respectively. CONCLUSION: Hysteroscopy is a safe and effective minimally invasive procedure with very low complication rate. PMID- 25134298 TI - Effects of natural progesterone on endometriosis in an experimental rat model: is it effective? AB - To assess the effects of the natural progesterone on the endometriosis in a rat model. MATERIALS AND METHODS: Endometriosis was surgically induced in 20 rats by transplanting an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. Rats in control group had no medication but 2.5 mg/kg/weekly natural progesterone was administered to rats in study group for four weeks. After that, all rats were sacrificed and dimensions of endometriosis were measured and they were evaluated morphologically and histologically. Scoring systems were used to evaluate preservation of epithelia. RESULTS: Two rats in the study group and one rat in the control group died of complications related to surgery. At the end of the treatment, there was a reduction in the size of the endometriotic lesions in the study group (p < 0.01). According to histological evaluation, the study group had lower score than control goup which was statistically significant (p = 0.014). CONCLUSIONS: Natural progesterone is effective against endometriosis in rat model. PMID- 25134299 TI - Marked improvement of the autoimmune syndrome associated with autoimmune hepatitis by treatment with sympathomimetic amines. AB - PURPOSE: To evaluate the effect of sympathomimetic amine therapy for a life threatening autoimmune disorder. MATERIALS AND METHODS: Dextroamphetamine sulfate was used to treat edema, myalgia, and chronic fatigue associated with autoimmune hepatitis (AIH). RESULTS: Sympathomimetic amine therapy completely abrogated the symptoms associated with AIH. CONCLUSIONS: AIH should be added to the long list of chronic treatment-refractory conditions that respond quickly and effectively to treatment with sympathomimetic amines. PMID- 25134300 TI - Abdominal intrauterine vacuum aspiration. AB - Evaluating and "cleaning" of the uterine cavity is probably the most performed operation in women. It is done for several reasons: abortion, evaluation of irregular bleeding in premenopausal period, and postmenopausal bleeding. Abortion is undoubtedly the number one procedure with more than 44 million pregnancies terminated every year. This procedure should not be underestimated and a careful preoperative evaluation is needed. Ideally a sensitive pregnancy test should be done together with an ultrasound in order to confirm a uterine pregnancy, excluding extra-uterine pregnancy, and to detect genital and/or uterine malformations. Three out of four abortions are performed by surgical methods. Surgical methods include a sharp, blunt, and suction curettage. Suction curettage or vacuum aspiration is the preferred method. Despite the fact that it is a relative safe procedure with major complications in less than one percent of cases, it is still responsible for 13% of all maternal deaths. All the figures have not declined in the last decade. Trauma, perforation, and bleeding are a danger triage. When there is a perforation, a laparoscopy should be performed immediately, in order to detect intra-abdominal lacerations and bleeding. The bleeding should be stopped as soon as possible in order to not destabilize the patient. When there is a perforation in the uterus, this "entrance" can be used to perform the curettage. This is particularly useful if there is trauma of the isthmus and uterine wall, and it is difficult to identify the uterine canal. A curettage is a frequent performed procedure, which should not be underestimated. If there is a perforation in the uterus, then this opening can safely be used for vacuum aspiration. PMID- 25134301 TI - Salmonella ovarian abscess in a patient with rheumatoid arthritis (RA): a case report with literature review. AB - Salmonella ovarian abscess in a patient with rheumatoid arthritis (RA) is reported here. A 33-year-old nulliparous woman with a 16-year history of RA who had been treated with corticosteroid and immunosuppressive drugs was diagnosed as having a non-typhoidal Salmonella ovarian abscess which might have been preceded by an occurrence of endometriotic cyst. Multidisciplinary therapy including surgical intervention was required to complete the eradication of infection. Although Salmonella ovarian abscess is rare, it may cause a serious complication in the ovary harboring endometriotic cyst through sustained presence of Salmonella bacteraemia. PMID- 25134302 TI - Transient sixth cranial nerve palsy following orgasm abrogated by treatment with sympathomimetic amines. AB - PURPOSE: To describe a unique disorder where a transient 6th nerve palsy leading to diploplia following orgasm developed in a 28-year-old woman. This coincided with a weight gain of 100 pounds in a short time without a corresponding change in dietary habits. MATERIALS AND METHODS: She was treated with the sympathomimetic amine dextroamphetamine sulfate. RESULTS: Indeed she immediately responded to treatment with dextroamphetamine sulfate sustained release capsules with complete resolution of the episodes of 6th nerve palsy following orgasm. CONCLUSIONS: The main importance of this case is that it suggests that orgasm causes a transient generalized decrease in sympathetic nervous system activity and that the achievement of an orgasm may require an increase in the sympathetic nervous system activity. PMID- 25134303 TI - Normal evolution of pregnancy complicated by a giant placental chorioangioma. AB - Placental chorioangioma is a benign vascular tumour of placental origin. Here The authors report a case of a pregnant patient who presented placental chorioangioma measuring 11 cm in the greatest diameter at 37 weeks at term and in labor. PMID- 25134304 TI - Failure to improve a thin endometrium in the late proliferative phase with uterine infusion of granulocyte-colony stimulating factor. AB - PURPOSE: To determine if the treatment with uterine infusion of granulocyte colony-stimulating factor (G-CSF) can improve endometrial thickness in an infertile woman with a double uterus, who consistently showed a thin endometrium in the late proliferative phase either in controlled ovarian hyperstimulation (COH) IVF-ET cycles or with graduated estrogen/sildenafil protocols for frozen embryo transfer (ET). MATERIALS AND METHODS: A single uterine infusion of G-CSF was performed in the late proliferative phase in a woman who only attained a five mm thickness despite a high dose vaginal and oral estradiol regimen plus sildenafil. RESULTS: No increase was found within a couple days. CONCLUSIONS: A previous four-case study in another center found 100% improvement in the endometrial thickness in women with consistently thin endometria. Perhaps the uterine anomaly in the present case prevented the response of the endometrium. PMID- 25134305 TI - Uterine inversion after controlled cord traction during caesarean section: a case report. AB - INTRODUCTION: Inversion of the uterus during caesarean section is a rare but life threatening complication of the procedure that requires immediate treatment, which is reversion and awareness due to the very serious adverse effects that it may have. MATERIALS AND METHODS: The authors present a case of a 34-year-old para 1 woman of Greek ethnicity who underwent a scheduled caesarean section at 39 weeks of gestation. During the procedure, a uterine inversion occurred as a controlled cord traction was applied in order to achieve placental detachment, after the delivery of the baby. It was managed by immediate manual uterine reversion, which was performed after exteriorization of the uterus. There were no adverse effects. CONCLUSION: Uterine inversion during caesarean section is a serious complication, but fortunately very rare. However, the obstetrician should be aware that the complication should be quickly identified and act without hesitation because it is critical for the well being of the patient. PMID- 25134306 TI - Sympathomimetic amine therapy found effective for treatment of refractory chronic complex regional pain syndrome (reflex sympathetic dystrophy). AB - PURPOSE: To determine if treatment with sympathomimetic amines could improve the pain from complex regional pain disorder (CRPD) which was keeping a woman from trying to conceive her second child. MATERIALS AND METHODS: Dextroamphetamine sulfate was prescribed. RESULTS: Within a short length of time the woman's wrist pain considerably improved to the point that she is ready to try in vitro fertilization once again to have a second baby. CONCLUSIONS: Though sympathomimetic amines are used by some reproductive endocrinologists for unexplained infertility and unexplained recurrent miscarriages, the most common use by the gynecologist is for pelvic pain. Despite the thought by some clinicians and researchers that the etiology for CRPD may be related to sympathetic nervous system hyperactivity (and thus sympathomimetic amines could theoretically exacerbate the symptoms), in fact, the treatment with dextroamphetamine sulfate may turn out to be a new and possibly the most effective, least risky, and least expensive treatment to date for CRPD. PMID- 25134307 TI - Pallister-Killian syndrome in a preterm newborn who died soon after precipitous delivery: cytogenetic analysis. AB - The authors report a preterm neonate with dysmorphic traits and cleft palate who was born preterm because of precipitous delivery and died soon after birth notwithstanding neonatal intensive care unit (NICU) support. The cytogenetic analysis on fibroblasts from post-mortem skin biopsy demonstrated a Pallister Killian syndrome (PKS). PKS is a cytogenetically syndrome characterized by a tissue limited mosaic distribution of one isochromosome 12p (tetrasomy 12p). Clinical manifestations of PKS are variable, and some symptoms may overlap with other malformative syndromes, thus the correct diagnosis mainly depends on the demonstration of the specific cytogenetic abnormality. PMID- 25134309 TI - Cutaneous reactions to bed bug bites. PMID- 25134308 TI - Spontaneous cutaneous umbilical endometriosis: a rare variant of extragenital endometriosis. AB - Umbilical endometriosis is a very uncommon condition which presents as a pigmented umbilical nodule, papular or cystic, with symptoms punctuated rhythmed by menses. The authors report the case of a 32-year-old with spontaneous umbilical endometriosis. Surgical resection was performed with a good cosmetic result and no recurrence at six months. A review of the literature allowed the authors to discuss the diagnosis difficulties and treatment in a underdeveloped country. PMID- 25134310 TI - Low-level laser/light therapy for androgenetic alopecia. AB - Androgenetic alopecia (AGA) is a persistent and pervasive condition that affects men worldwide. Some common treatment options for AGA include hair prosthetics, oral and topical medications, and surgical hair restoration (SHR). Pharmaceutical and SHR treatments are associated with limitations including adverse side effects and significant financial burden. Low-level laser or light (LLL) devices offer alternative treatment options that are not typically associated with adverse side effects or significant costs. There are clinic- and home-based LLL devices. One home-based laser comb device has set a standard for others; however, this device requires time devoted to carefully moving the comb through the hair to allow laser penetration to the scalp. A novel helmet-like LLL device for hair growth has proven effective in preliminary trials and allows for hands-free use. Regardless, there are few clinical trials that have been conducted regarding LLL devices for AGA and results are mixed. Further research is required to establish the true efficacy of these devices for hair growth in comparison to existing alternative therapies. PMID- 25134311 TI - Motives for cosmetic procedures in Saudi women. AB - The media-fuelled obsession with beauty in modern society has led more women to seek elective cosmetic procedures to meet the portrayed ideals of beauty in different cultures. This study gives insights into incentives and desires to undergo cosmetic procedures in a conservative society with strict religious practices where women are veiled. Questionnaire data were obtained from 509 Saudi women who responded to a survey distributed randomly to a sample of Saudi women aged 17 to 72 years. At least 1 elective cosmetic procedure was performed in 42% of the women, of whom 77.8% wore a veil. Another 33% considered having a procedure. The motives for seeking a cosmetic procedure were to improve self esteem in 83.7%, attract a husband in 63.3%, or prevent a husband from seeking another wife in 36.2%. The decision to seek a procedure was affected by the media, with high peer influence. Motivation for elective cosmetic procedures in Saudi women is influenced by a combination of emotional and cultural factors, level of education, marital status, and religious beliefs. The veil is not an impediment for seeking such procedures. The limitation of the study was missing data analysis as some items in the questionnaire were completed inaccurately or left unanswered. PMID- 25134313 TI - Cutaneous malignancies in immunosuppressed organ transplant recipients. AB - During the past century, organ transplantation has delivered the miracle of life to more than 500,000 patients in need. Secondary malignancies have developed as an unforeseen consequence of intense immunosuppressive regimens. Cutaneous malignancies have been recognized as the most frequent cancer that arises post transplantation. Among organ transplant recipients (OTRs), skin cancer is a substantial cause of morbidity and potential mortality. The authors discuss epidemiology and clinical presentation of cutaneous malignancies; associated risk factors; recommendation for the care of immunosuppressed OTRs, and emerging therapies on the horizon. PMID- 25134312 TI - A high glycerol-containing leave-on scalp care treatment to improve dandruff. AB - Dandruff is a common cosmetic condition associated with flaky scalp skin and pruritus. It is generally treated with regular use of antifungal-based shampoos. Research into factors underlying the characteristic skin lesions has revealed perturbations in epidermal differentiation and a dramatic deterioration in the associated process of stratum corneum (SC) maturation. These observations suggest that directly addressing the quality of the SC could have a scalp benefit. In this study, the authors investigated the efficacy of a moisturising leave-on lotion (LOL) containing a high concentration of glycerol (10%) and other known skin benefit agents (saturated fatty acid and sunflower seed oil) to reduce dandruff over an 8-week treatment period with 3 applications per week. Results of expert visual grading and biophysical measurements of SC parameters (transepidermal water loss and hydration) revealed a significant reduction in the dandruffcondition over this period, with significant improvement in both SC water barrier function and hydration. These scalp skin benefits were maintained for up to a week following cessation of the treatment. This study indicates that use of a glycerol-rich substantive LOL, designed to directly improve the quality of the SC barrier can have a significant impact on the dandruff condition. PMID- 25134314 TI - Basal cell carcinoma: pathophysiology. AB - Basal cell carcinoma (BCC) is the most common skin cancer in humans, which typically appears over the sun-exposed skin as a slow-growing, locally invasive lesion that rarely metastasizes. Although the exact etiology of BCC is unknown, there exists a well-established relationship between BCC and the pilo-sebaceous unit, and it is currently thought to originate from pluri-potential cells in the basal layer of the epidermis or the follicle. The patched/hedgehog intracellular signaling pathway plays a central role in both sporadic BCCs and nevoid BCC syndrome (Gorlin syndrome). This pathway is vital for the regulation of cell growth, and differentiation and loss of inhibition of this pathway is associated with development of BCC. The sonic hedgehog protein is the most relevant to BCC; nevertheless, the Patched (PTCH) protein is the ligand-binding component of the hedgehog receptor complex in the cell membrane. The other protein member of the receptor complex, smoothened (SMO), is responsible for transducing hedgehog signaling to downstream genes, leading to abnormal cell proliferation. The importance of this pathway is highlighted by the successful use in advanced forms of BCC of vismodegib, a Food and Drug Administration-approved drug, that selectively inhibits SMO. The UV-specific nucleotide changes in the tumor suppressor genes, TP53 and PTCH, have also been implicated in the development of BCC. PMID- 25134315 TI - New wine in old bottles: the coming deluge of aggressive cutaneous cancers and precancers. PMID- 25134316 TI - Hot topics in the cosmetics industry. PMID- 25134317 TI - Kafka and the enigmatic case of cutaneous myiasis. PMID- 25134318 TI - A rare case of aplasia cutis with vanishing twin syndrome and unusual presentation. PMID- 25134319 TI - The challenge of managing increasingly complex cancer toxicity. PMID- 25134320 TI - It's time to have 'the talk': cost communication and patient-centered care. PMID- 25134321 TI - Cardiovascular toxicity of biologic agents for cancer therapy. AB - There has been significant progress in the development of new anticancer therapies over the last decade.Targeted therapies, including anti-human epidermal growth factor receptor 2 agents, vascular endothelial growth factor inhibitors, and tyrosine kinase inhibitors, have been important components of current treatment strategies. However, many of these therapies have been associated with chemotherapy-related cardiac dysfunction. While newer targeted agents provide "on target" anticancer activity, their "off-target" drug effects encompass a wide range of cardiovascular toxicities. Many of these toxicities are reversible, but they may limit the use and length of treatment and compromise its efficacy. Oncologists are often the first to diagnose chemotherapy-related cardiac dysfunction, although patients with advanced cardiotoxicity are referred to cardiologists for further care. The field of cardio-oncology has emerged as a necessary discipline to address these disabling complications. In order to prevent late-stage cardiotoxicity, an early collaborative effort between oncologists and cardiologists is warranted to risk-stratify patients prior to therapy and to treat at the earliest signs of cardiotoxicity. It is therefore of utmost importance for oncologists to be aware of the cardiotoxicities of anticancer therapies, and to be familiar with modifiable risk factors and early interventions that can prevent long-term cardiac damage. PMID- 25134322 TI - Cardiotoxicity of targeted agents in oncology: a medical oncology perspective. PMID- 25134323 TI - Cardiovascular toxicity of Newer chemotherapeutic agents: the heart of the matter. PMID- 25134324 TI - Salvage chemotherapy for refractory germ cell tumors. PMID- 25134325 TI - Esophagogastric junction and gastric adenocarcinoma: neoadjuvant and adjuvant therapy, and future directions. AB - In North America, gastric cancer is the third most common gastrointestinal malignancy and the third most lethal neoplasm overall. In Asia, gastric cancer represents an even more serious problem: in Japan, it is the most common cancer in men. The standard primary therapy for gastric cancer is surgical resection; in esophagogastric-junction (EGJ) adenocarcinoma, which is often included in studies of gastric cancer, surgery is also typically the initial management strategy. However, the rates of locoregional and distant recurrence following surgery with curative intent have remained high. Investigators have explored a variety of ways of reducing these rates and improving survival in patients with gastric and EGJ cancers. These strategies have included explorations of the optimal extent of regional lymphadenectomy at the time of gastric resection; investigation of different neoadjuvant, perioperative, and adjuvant chemotherapy regimens; use of preoperative and postoperative radiation therapy; and the use of pre- and postoperative chemoradiotherapy (CRT).To date, benefit has been seen in gastric cancer patients with the use of what is called a"D2 resection"(which includes lymph nodes of stations 7 through 12) and with adjuvant CRT (in the West) or adjuvant chemotherapy with S-1 (in Japan); and neoadjuvant CRT has been shown to have a survival benefit in patients with EGJ cancers. PMID- 25134326 TI - EGJ and esophageal cancers: choosing induction therapy so as to err on the side of overtreatment rather than undertreatment when staging is imperfect. PMID- 25134327 TI - Esophagogastric junction and gastric adenocarcinoma: current challenges and future directions. PMID- 25134328 TI - The role of radical prostatectomy and lymph node dissection in the treatment of young men with high-grade node-positive prostate cancer: there may be no RCTs-but there are good reasons to include surgery. PMID- 25134329 TI - The role of radical prostatectomy and lymph node dissection in the treatment of young men with high-grade node-positive prostate cancer: less is more--the benefits of surgery do not yet outweigh potential harms. PMID- 25134330 TI - Double trouble: a case of concurrent de novo T790M and L858R EGFR mutations in treatment-naive advanced non-small-cell lung cancer. PMID- 25134331 TI - My love-hate relationship with hospitals. PMID- 25134332 TI - Survivorship is not a passive sport. PMID- 25134333 TI - Hypofractionation for breast cancer: lessons learned from our neighbors to the north and across the pond. AB - Adjuvant whole breast irradiation was established within the standard of care for breast-conserving therapy in the early 1980s, following the results of major randomized trials comparing mastectomy vs breast-conserving surgery and radiation. Since that time, techniques and treatment strategies have evolved, but one major thread that carries forward is the need to balance cost, efficacy, complications, and convenience. Fortunately, data from randomized trials conducted in Canada and Great Britain provide a solid framework for the consideration of hypofractionated radiation in the treatment of breast cancer. In this review we discuss the rationale and underlying radiobiologic concepts for hypofractionation, and review the clinical trials and American Society for Radiation Oncology (ASTRO) guidelines supporting this approach. We also review the practical considerations for treatment planning, including dosimetric criteria and how to approach treatment of the node-positive patient. In the current era of healthcare reform and cost awareness, thoughtful utilization of hypofractionation may offer considerable savings to individual patients and the healthcare system--without compromising clinical outcomes or quality of life. PMID- 25134334 TI - Fractionation in breast cancer radiotherapy for conservative treatment: are we really done learning? PMID- 25134335 TI - Consider a single intraoperative fraction for patients eligible for hypofractionated regimens? PMID- 25134336 TI - Distribution and heterogeneity of heterochromatin in the European huchen (Hucho hucho Linnaeus, 1758) (Salmonidae). AB - The chromosomal characteristics, locations and variations of the heterochromatin were studied in the European huchen (Hucho hucho, Linnaeus, 1758) karyotype using conventional C- banding, endonuclease digestion banding, silver nitrate (AgNO3), chromomycin A3 (CMA3) and DAPI staining techniques. The karyotype consists of 82 chromosomes: 13 pairs of metacentric chromosomes, 2 pairs of submetacentric chromosomes and 26 pairs of subtelo-acrocentric chromosomes (NF = 112). Original data on the chromosomal distribution of segments resistant to Alu I, Dde I and Mbo I restriction endonucleases and identification of the C-banded heterochromatin presented here have been used to characterize the huchen karyotype. On the basis of the banding patterns provided in the course of restriction enzyme digestion, AgNO3/CMA3 staining and C-banding we distinguished twelve types of heterochromatin grouped in four areas of the European huchen chromosomes. One pair of NOR-bearing chromosomes was found to be polymorphic in size and displayed two distinct forms. A combination of various staining techniques provided original data concerning heterochromatin distribution and heterogeneity in the European huchen which enabled better karyotypic definition of this fish species. PMID- 25134337 TI - Molecular variability of the COI fragment supports the systematic position of Enarmoniini within the subfamily Olethreutinae (Lepidoptera: Tortricidae). AB - The Tortricidae, a globally distributed family of Lepidoptera, consists of approximately 10,000 described species, of which a large number do not have clearly defined taxonomic positions. In the present paper the systematics of Enarmoniini based on molecular data is compared to systematics based on morphology. Two genera of Enarmoniini were used for analysis: the type-genus Enarmonia (one species examined) and Ancylis (7 species examined). A comparison of a 606 bp homologous fragment of the COI mitochondrial gene revealed that Enarmoniini form a cluster distinct from Olethreutini (3 genera and 7 species examined), Eucosmini (2 genera, 4 species) and Grapholitini (4 genera, 9 species). In our opinion the molecular studies combined with previously obtained morphological data should facilitate a more natural classification system of this relatively poorly explored family of Microlepidoptera. Altogether, 30 species of Tortricidae were examined. PMID- 25134338 TI - Estimation of global content of 5-methylcytosine in DNA during allantoic and pulmonary respiration in the chicken embryo. AB - DNA methylation is an epigenetic modification that plays an important role in the proper development and functioning of an organism. The DNA methylation level is species-, tissue- and organelle-specific, and the methylation pattern is determined during embryogenesis. A correlation between methylation and age is also observed. Epigenetic phenomena are an enormously interesting research subject, not only from the perspective of pure science, but also due to their possible applications in medicine. The aim of this study was to determine the global DNA methylation level in relation to the developmental stage of the embryo. The global level of 5-methylcytosine in the DNA during pulmonary respiration was found to be higher than during allantoic respiration. The analysis shows a clear dependence between the stage of individual development and the global DNA level of 5-methylcytosine. In the future, methylation level may be a determinant of age and perhaps even a tool for predicting life expectancy. Abnormalities in the methylation process result in premature ageing at the cellular and individual level. PMID- 25134339 TI - The fatty acid profile of muscle tissue of ram lambs with diverse genotypes. AB - The aim of the study was to determine the fatty acid profile of intramuscular fat for genetically diverse sheep breeds kept in the same environmental and feeding conditions. The study was conducted on 30 (15 in each breed) wrzosowka and zelaznenska ram lambs slaughtered at 23-25 kg of life weight. The meat samples for analysis were taken from longissimus lumborum muscle. The meat of wrzosowka ram lambs contained almost twofold less (P < or = 0.01) intramuscular fat compared to zelaznenska sheep. Lower (P < or = 0.05) total of SFA and higher (P < or = 0.05) MUFA content in muscle tissue of wrzos6wka sheep was shown. The predominant monounsaturated acid was oleic acid which amounted to almost 90% of all MUFA. The activity of enzyme Delta9 desaturase evidenced by the higher values of C14:1/C14:0, C18:1/Cl8:0 (P < or = 0.01) and C16:1/C16:0 (P < or = 0.05) indices was also recorded for wrzos6wka ram lambs. The UFA/SFA (P < or = 0.05) and MUFA/SFA (P < or = 0.05) ratios as well as the value of the trombogenic index (TI) (P < or = 0.05) were more favourable in muscle tissue for wrzos6wka than zelaznenska rams lambs. Therefore, the meat from leaner animals is more beneficial for human health. PMID- 25134340 TI - Reproductive performance of New Zealand White rabbits after depletion of apoptotic spermatozoa. AB - The objective of this study was to assess the utility of the magnetic-activated cell sorting (MACS) technique used for improving characteristics and quality of insemination doses by the elimination ofapoptotic rabbit spermatozoa from a heterospermic pool (Experiment 1) as well as from the ejaculates of individual bucks (Experiment 2). Superparamagnetic microbeads conjugated with annexin V eliminated spermatozoa with externalized phosphatidylserine via MACS. The control (untreated) and magnetically separated spermatozoa (in both E1 and E2) were used for artificial insemination of hormonally treated rabbit does. MACS separation of spermatozoa yielded two fractions: annexin V-negative (AnV) and annexin V positive (AnV+). The CASA analysis after MACS sperm sorting revealed that the proportion of apoptotic spermatozoa in the semen of New Zealand White bucks varied from 7 to 20%. Transmission electron microscopy revealed that MACS treatment might eliminate spermatozoa with membrane damages and released acrosomal matter. However, the MACS separation (in both E1 and E2) did not affect the reproductive parameters of rabbit does. PMID- 25134341 TI - The effect of mammary gland-specific transgene expression on rabbit reproductive gland structure. AB - Transgenic rabbits are excellent animal models for human diseases and suitable bioreactors for the production of recombinant proteins on an experimental and commercial scale. The aim of this study was to compare the structure of the mWAP hFVIII transgenic and non-transgenic rabbit ovarian and testicular tissue. Ovarian and testicular tissue samples were taken from transgenic and non transgenic New Zealand White rabbits, examined by optical microscopy and analyzed morphometrically. An increase of the relative volume of primary follicles and a decrease of the relative volume of antral follicles was detected in the transgenic ovarian structure (P < 0.05), but other developmental follicular stages and follicular diameters were not affected (P > 0.05). In the testes a significant decrease (P < 0.05) of the epithelial height was detected in the transgenic testicular structure, but the relative volume of all basic structures (germinal epithelium, interstitium and lumen) was unaltered (P > 0.05). Generally, this study demonstrates a weak negative effect of mWAP-hFVIII transgenesis on rabbit gonadal structure. PMID- 25134342 TI - The effect of different fat sources in the diet on the composition of adipose tissue in arctic foxes (Alopex lagopus L.). AB - The study investigated the effect of vegetable and animal fat in the feed ration on the fatty acid profile of reserve fat in the arctic fox. Varying proportions of saturated and unsaturated fats in the feed ration comprised the experimental factor. In order to differentiate contents of saturated and unsaturated fatty acids in the experimental feed rations, various percentages of rapeseed oil and turkey fat were applied. The subcutaneous and circum-organal fat in this study differed considerably in terms of contents of individual fatty acids and between individual groups of acids. The circum-organal fat contained much higher amounts of unsaturated acids, but at the same time it was characterized by a lower amount of monounsaturated acids. Significant differences were also found in the contents of as many as 11 fatty acids. Recorded results indicate a potential modification of reserve fat in the arctic fox, a model representative of carnivorous animals (Carnivora). The possibility of the partial substitution of animal fat with vegetable oil (rape oil) in the nutritive diet of artic foxes was confirmed. PMID- 25134343 TI - Sexual maturation in common vole (Microtus arvalis) males raised under laboratory conditions. AB - The common vole is one ofthe most numerous rodents in Europe and Asia but its reproductive biology is not fully described. It is thought that females reach reproductive abilities at a very young age, however, there is no data concerning male sexual maturation. The aim of the present study was to determine the rate of sexual maturation of males of the common vole. Research was carried out on 4, 6, 8 and 10 week-old animals. Body, testes and accessory sex glands weights were compared to evaluate morphological development. Epididymal sperm quality was assessed by a motility test, sperm tail membrane integrity, viability, maturity and sperm head morphology. Moreover, the number of sperm cells in 1 mm3 of semen was evaluated. The largest body weights were observed in 8 and 10 week-old males, which also possessed the highest relative weights of gonads and accessory sex glands. These groups of males produce about 2 times more gametes than 6 week-old individuals. The highest seamen quality was noted in 8 and 10 week-old males. Based on the obtained results, it is concluded that among the investigated age groups the most appropriate male age for fertile copulation is between 8 and 10 weeks. PMID- 25134344 TI - Are chondroclasts and osteoclasts identical? AB - Brief characteristics of cells termed "osteoclasts" and "chondroclasts" are outlined and reasons to consider them as the same cell type, able to resorb calcified matrix, are discussed. PMID- 25134345 TI - The effect of saprotrophic fungi on the development and hatching of Fasciola hepatica eggs. AB - The aim of this study was to determine the effect of 6 common soil fungi species: Alternaria alternata (Fr.) Keissl., Aspergillus candidus Link, Penicillium chrysogenum Thom, P. commune Thom, Trichothecium roseum (Pers.) Link and Ulocladium sp., on the hatching of miracidia, i.e., free living larvae of liver fluke (Fasciola hepatica). To this end, the eggs of F. hepatica were incubated in water in the presence of one of the aforementioned fungi species and in tap water (control) at a temperature of 26 degrees C. At the 15th day of incubation we determined the number of nonembryonated, embryonated and hatched eggs. We observed different degrees of antagonistic influences by the tested fungal strains on the development of F. hepatica eggs. Among the examined fungi, the strongest ovistatic effects were exhibited by Trichothecium roseum, Penicillium chrysogenum (R-3) and P. commune. The study showed no morphological damage to the shells of the F. hepatica eggs which may suggest a biochemical basis of antagonistic interactions by the fungi associated with the activity of fungal enzymes, mycotoxins and antibiotics. Low or no activity of peptide hydrolases in Penicillium chrysogenum and P. commune in the API ZYM test suggests their insignificant role in the degradation of shell proteins ofF. hepatica eggs. PMID- 25134346 TI - Effects of anesthetic compounds on responses of earthworms to electrostimulation. AB - Earthworms play an important role in biomedical research, and some surgical procedures require anesthesia. Anesthetic treatments used so far usually induce convulsive body movements connected with extrusion of coelomocyte-containing coelomic fluid that may affect experimental results. Extensive movements connected with the expulsion of coelomic fluid are exploited by immunologists as a method of harvesting immunocompetent coelomocytes from worms subjected to mild electrostimulation (4.5V). The aim of the investigations was to find anesthetic drugs without unintentional coelomocyte depletion. Experiments were performed on adult specimens of Dendrobaena veneta, the coelomocytes of which consist of amoebocytes and riboflavin-storing eleocytes. Earthworm mobility was filmed and extrusion of coelomocytes was quantified by detection of eleocyte-derived riboflavin in immersion fluid. Treatments included earthworms (1) immersed either in physiological saline (controls) or in a solution of one of the tested anesthetic drugs; (2) electrostimulated immediately after anesthesia, and (3) electrostimulated a second time after a 1-hour recovery period. The well established fish and amphibian anesthetic agent MS-222 induced coelomocyte expulsion. In contrast, solutions of the mammalian local anesthetic drug, prilocaine hydrochloride (0.25-0.5%, 5-10 min) caused temporal earthworm immobilization followed by recovery, thus showing utility as an efficient earthworm anesthetic. PMID- 25134348 TI - [Butterflies]. PMID- 25134347 TI - [In memory of Prof Lech Dzialoszynski (1912-2014) ]. PMID- 25134349 TI - [Aging and longevity]. AB - During the last three centuries the expected lifespan in civilized countries has increased several times. The fastest growing groups are seniors (65+) and centenarians. Increased lifespan results in postponing of aging and age-related diseases. On the other hand, an increase in the number of people suffering from age-related diseases can be observed. Studies concerning longevity and aging help to elucidate the mechanisms responsible for these processes and give hope for finding the recipe for a healthy and long lifespan. Aging and longevity are modulated by genetic, epigenetic and stochastic factors. Already some variants of genes which correlate with longevity are known. Products of these genes are involved in lipid metabolism and in nutrient sensing signaling pathways such as: insulin/IGF-1 and TOR. Good indicators for human polymorphism study are results obtained using model organisms such as S. cerevisiae, C. elegans, D. melanogaster and laboratory mice. Aging and longevity are evolutionary conserved. Evolutionary theories concerning aging can be divided into two general categories: programmed and non-programmed ones. According to programmed theories aging is adaptive and can lead to altruistic death of kins. Non-programmed theories predict that organisms only have a limited amount of energy that has to be divided between reproductive activities and the maintenance of the non-reproductive aspects of the organism. Aging is the effect of natural degrading processes that result in the accumulation of damage. Accumulation of damaged DNA and proteins can lead to cellular senescence, inflammaging and age-related diseases. Strategies for postponing aging mainly rely on protecting and/or eliminating these lesions. PMID- 25134350 TI - [Markers of cellular senescence]. AB - Cellular senescence is a complex process associated with irreversible cell cycle arrest. We can distinguish replicative senescence, which is telomere dependent and stress-induced premature senescence (SIPS), which is telomere independent. Replicative senescence can be observed in culture after a few weeks or months, depending on the cell type. On the other hand SIPS can be observed a few days after treating with a senescence inducing agent. Till now a universal marker of senescence has not been decribed. Studies concerning senescence are possible thanks to the existance of many markers of senescence which enable to observe molecular as well as biochemical changes associated with this process. The presence of a few markers of senescence allows us to be sure that cells underwent senescence. PMID- 25134351 TI - [Impact of cellular senescence on organismal aging and age-related diseases]. AB - Development of the civilization and medicine enables an even longer lifespan of people. To modulate the aging process it is necessary to discover its molecular mechanism and its causes. It has been known for almost 60 years that cells undergo senescence. A lot of markers of senescence have been described to distinguish senescent cells. Every year we can observe an increase in the number of data, supporting the thesis that the reason for aging of the whole organism is cellular senescence. We age because cells building tissues and organs undergo senescence. It is also believed that cellular senescence can increase the frequency of age-related diseases. The role of cellular senescence strictly depends on the age of the individual. In young ones it is essential for: protection against cancer and tissue regeneration. In old ones it causes tissues and organs dysfunctions and leads to age-related diseases. Slowing down aging could prevent age-related diseases and this seems to be more promising than curing them. To enrich our knowledge concerning aging it is important to understand signaling pathways leading to senescence. Recently a new role of cellular senescence has been discovered, namely during embryogenesis. This observation is very surprising and shows a new face of cellular senescence. It is possible that, similarly to the previously described role of apoptosis in embryogenesis, senescence is indispensable for proper organogenesis. Cellular senescence seems to be the universal and fundamental process, the role of which changes during the lifespan. PMID- 25134352 TI - [Stem cells and senescence]. AB - Stem cells are undifferentiated cells that can differentiate into specialized cells, that build the whole body. These rare cells are required for homeostasis and tissue replacement throughout the human lifespan, and appear to be characterized by a few specific physiological and biochemical properties, particularly the capacity for self-renewal. Recent studies suggest that stem cells may undergo senescence, what plays a crucial role in organismal aging. Importantly, both senescence and apoptosis are anti-cancer mechanisms that counteract neoplastic transformation of stem cells. On the other hand, mechanisms that suppress the development of cancer may also induce an unwanted consequence: a decline in the number and functional alterations of stem cells with advancing age. These functional changes reflect harmful effects of age on the genome, epigenome, and proteome of stem cells. Some of which arise cell independently and others which are imposed by an age-related change in the local milieu or systemic environment. Remarkably, some of the changes, particularly epigenomic and proteomic ones, are potentially reversible, and both environmental (e.g. caloric restrictions, hypoxia) and genetic interventions can lead to inducible pluripotency. Here, we discuss recent discoveries in the field of senescence of stem cells. These findings have profound implications, not only for our understanding of stem cells' biology and organismal aging, but also for stem cell based regenerative medicine and stem cell-based therapy of age-related diseases. PMID- 25134353 TI - [Neuronal ageing]. AB - Ageing leads to irreversible alterations in the nervous system, which to various extent impair its functions such as capacity to learn and memory. In old neurons and brain, similarly to what may take place in other cells, there is increased oxidative stress, disturbed energetic homeostasis and metabolism, accumulation of damage in proteins and nucleic acids. Characteristic of old neurons are alterations in plasticity, synaptic transmission, sensitivity to neurotrophic factors and cytoskeletal changes. Some markers of senescence, whose one of them is SA-beta-galactosidase were used to show the process of neuronal ageing both in vitro, and in vivo. Some research suggest that, despite the fact that neurons are postmitotic cells, it is cell cycle proteins which play a certain role in their biology, e.g. differentiation. However, their role in neuronal ageing is not known or explained. Ageing is the serious factor of development of neurodegenerative diseases among others Alzheimer disease. PMID- 25134354 TI - [Senescence of mesothelial cells]. AB - The mesothelium is a specific group of cells having characteristics of both mesenchymal and epithelial cells. One of the most unique properties of these cells is a low proliferative capacity and a small number of achievable division. The purpose of this paper was to present the current state of knowledge on the causes of premature senescence of peritoneal mesothelial cells and to discuss the molecular events involved in this process. Particular attention was paid to the role of telomeres, the activity of senescence effectors at the level of the cell cycle, and the action of oxidative stress and transforming growth factor beta1. Moreover, the relationship between senescence of mesothelial cells and the aging of the organism as a whole, as well as the participation of senescent cells in the development of the intraperitoneal cancer metastasis was addressed. PMID- 25134355 TI - [The role of cellular senescence in carcinogenesis and antitumor therapy]. AB - Cellular senescence is the process that lead to terminal growth arrest induced by unrepairable double strand DNA damage (DSB). Moreover, activation of the oncogenes as well as inhibition of the tumor suppressor genes were shown to contribute to senescence induction and the senescent cells were identified in the premalignant lesions. Thus senescence is considered as an natural antitumor barrier that act at the early stages of cancerogenesis to stop the proliferation of transformed cells. Interestingly, the premalignant cells that escaped senescence and progress into full blown tumor cells still remain sensitive to induction of senescence, for example during chemio- or radiotherapy. Thus, induction of cancer cell senescence, similarly to apoptosis, is considered to restrain tumor growth and thus contribute to effectiveness of anticancer therapy. The senescent cells, although do not proliferate, remain viable and metabolically active. They secret a lot of cytokines, mitogens as well as enzymes degrading extracellular matrix. These factors can have opposing effect on neighboring cells, leading to senescence induction or stimulation of proliferation. Thus, senescence can act as an double edge sword that inhibit the propagation of potentially dangerous, transformed cells on one hand or induce cell division of the same cell on the other. Presently a lot of work is focused on finding new therapeutic strategies that would involve the tumor targeted senescence induction in both early late stages of cancer development. Nevertheless, the unwanted influence of the senescent cells on the microenvironment, requires careful monitoring the effects of pro-senescent therapies in each case. PMID- 25134356 TI - [Natural compounds--modulators of senescence and cell death]. AB - For hundreds of years natural compounds have been used in herbal medicine. They have been known for their antibacterial, antifungal, anticancer activities as well as for enhancing wound healing and improving immunity. Recently growing interest in natural compounds has been observed, due to their ability to modulate cellular senescence. Particularly interesting are these compounds that can induce tumor senescence, delay senescence of normal cells or reverse changes associated with senescence - acting as "rejuvenation" agents. It has been shown that some of the natural compounds can both promote senescence of tumor cells as well as prevent it in normal cells. Thus, they can be useful in therapy of age-related diseases. Natural compounds can regulate nutrient and energy sensing signaling pathways that are involved in senescence. They can also influence the synthesis of reactive oxygen species, secretion of cytokines, telomere shortening or epigenetic changes of DNA. Natural agents often act in a pleiotropic manner. They can modulate cellular senescence in many ways e.g. by direct neutralization of free radicals and affecting other regulatory signaling pathways. Furthermore natural compounds, commonly used for years e.g. as spices, usually don't have any side effects. Therefore their use as dietary supplements or in long term therapy appears to be relatively safe. PMID- 25134357 TI - [Immunological theory of senescence]. AB - Senescence can result from decreased potential of the immune system to respond to foreign and self antigens. The most common effect is the inhibition to destroy dying and cancer cells and the decrease of the immune response to pathogens. Aging is closely related to inflammatory phenotype, which facilitate the development of age-related diseases. The mammal immune system is highly organized and adapted to react to a wide range of antigens. According to the immunological theory, the causative agents of senescence are multilevel changes of development and functions of immune cells. Some of changes can be beneficial for the maintenance of homeostasis and lifespan in continuously changing endogenous environment and immune history of the organism. PMID- 25134358 TI - [Mechanisms of the immune system ageing and some age-associated diseases]. AB - In this paper the concept of homeostenosis (progressive reduction of ability to adapt producing loss of effectiveness) of the immune system is presented as a cause of the system ageing. In particular, the progression of immune system homeostenosis was shown to be associated with previous or ongoing chronic inflammatory diseases, including rheumatoid arthritis, type 2 diabetes, chronic kidney disease and Alzheimer's disease. PMID- 25134359 TI - [The role of reactive oxygen species and mitochondria in aging]. AB - Aging is a biological phenomenon concerning all living multicellular organisms. Many studies have been conducted to identify the mechanisms underlying this process. To date, multiple theories have been proposed to explain the causes of aging. One of them is the free radical theory which postulates that reactive oxygen species (ROS), extremely reactive chemical molecules, are the major cause of the aging process. These free radicals are mainly produced by the mitochondrial respiratory chain as a result of electron transport and the reduction of the oxygen molecule. Toxic effects of ROS on cellular components lead to accumulation of oxidative damage which causes cellular dysfunction with age. The free radical theory has been one of the most popular theories of aging for many years. Scientific research on different model organisms aiming to verify the theory has produced abundant data, supporting the theory or, on the contrary, suggesting strong evidence against it. At present, the free radical theory of aging is no longer considered to be true. PMID- 25134360 TI - [The role of the DNA damage response in apoptosis and cell senescence]. AB - The genetic material is constantly subjected to DNA damage which is caused by physiological processes occuring in the cell and is exposed to exogenous DNA damaging agents. Eucariotic cells have developed a system called the DNA damage response (DDR), which is responsible for maintaining genomic inegrity. DNA damage can lead to senescence, DNA repair as well as to cell death. The key protein in the DDR pathway is p53. This protein undergoes numerous posttranslational modifications and can be involved in the activation of many genes and proteins leading to survival or cell death. In cell senescence the p53 protein leads to the induction of p21, which causes cell cycle arrest. In apoptosis p53 participates in the activation of caspases, which are responsible for the degradation of many proteins. PMID- 25134361 TI - Correction of bone and softtissue deformity of the single implant in the aesthetic zone: a case treated with alveolar ridge preservation, modified roll technique and a digitally coded healing abutment. AB - The correction of soft tissue deformity and aesthetic rehabilitation of a single implant in the aesthetic zone with a combination of periodontal and prosthodontic approaches is described. Soft tissue deformity was corrected resulting in significant soft tissue volume increase and eliminated the need for prosthetic gingival replacement. A two stage implant placement protocol, ridge preservation and a soft tissue augmentation flap design preserved epithelium attachment to the connective tissues. Use of a digitally coded healing abutment preserved the newly established soft tissue volume, allowed impression making without implant component removal, and minimized trauma to the newly established soft tissue architecture. PMID- 25134362 TI - Colour stability of acrylic resin denture teeth after immersion in different beverages. AB - The colour stability of acrylic resin denture teeth in beverages was investigated. A spectrophotometer measured the colour (CIE-L*a*b* system) of all specimens after storage in distilled water/for 24 h at 37 degrees C (T0). Specimens were then immersed in various beverages. After 15 days (T1) and 30 days (T2), for each material, the mean deltaE values were calculated and compared by two-way ANOVA and Tukey intervals (alpha = 0.05). In the deltaT0T1 period, specimens stored in red wine were significantly discoloured, compared to distilled water (P = 0.003). There was no difference between immersion solutions in deltaET0T2 (P = 0.772) and in deltaET1T2 (P = 0.058), and no difference between materials in all immersion periods. PMID- 25134363 TI - A hinged two-part partial denture used in conjunction with severely tilted teeth: a case report. AB - A two-part sectional denture can be a useful treatment option when the presence of severe hard tissue undercuts compromises the provision of a satisfactory conventional prosthesis. This article presents a case report illustrating the effective use of a hinged two-part denture in restoring a mandibular Kennedy Class IV edentulous area. A sectional denture approach was selected because of severe proximal and lingual undercuts. PMID- 25134365 TI - BSSPD Annual Conference. Apex Hotel, Dundee 14th - 15th April 2014. PMID- 25134364 TI - One-year clinical evaluation of a Glass Carbomer fissure sealant, a preliminary study. AB - Glass Carbomer is a new generation of restorative material developed from glass ionomer cements with possibility of gradual mineralization into fluorapatite. The aim of this clinical trial was to investigate the retention of Glass Carbomer fissure sealant after 12 months, in comparison to a commonly used conventional resin-based sealant. Forty-eight teeth in 24 patients [mean (SD) = 8 (2.3) years] with well-delineated fissure morphology were randomly divided into two equal groups and sealed with Bis-GMA resin-based Helioseal F (group A, Ivoclar Vivadent, Liechtenstein) and Glass Carbomer (group B, Glass Carbomer Sealant, Glass Carbomer Products, Leiden, Netherlands) using the split mouth design. Materials were placed and set according to the manufacturer's instructions using a polymerization unit Bluephase 16i (Vivadent, Liechtenstein). Complete sealant retentions in both groups were 100% and 75% after 6 and 12 months of clinical service, respectively. There were there were no secondary caries lesions in both groups after 6 months; two new carious lesions were detected in both groups after 12 months. The Mann-Whitney U test revealed no significant difference between the two groups at both evaluations points (P > 0.05). Glass Carbomer material showed a similar retention rate when compared with a resin-based sealant. Future studies are required to examine the long-term performance of Glass Carbomer sealants. PMID- 25134366 TI - Effect of preoxidation on the bond strength of titanium and porcelain. AB - The purpose of this study was to investigate the effect of preoxidation on porcelain titanium- bond strength and the effect of paste bonder (adhesive) on the titanium porcelain bond strength. 11 specimens of commercially pure titanium (26 x 7 x 3 mm) were prepared by different heat treatments in programmable dental furnace. Identification of the oxides formed on the metal surface was conducted with an X-Ray diffractometer with CuKalpha radiation. Vickers hardness numbers were determine. Additional 50 specimens of commercially pure titanium were used to bond with low fusing porcelain. The bond strength was measured in a universal testing machine. X-ray diffraction analysis of the surface of pure titanium revealed that the relative peak intensity of alpha -Ti decreased and that of TiO2 increased with increasing firing temperature. The Vickers hardness number decreased initially as the temperature increased but it increased remarkably above 900 degrees C & was harder in air than vacuum. The tensile shear bond strength was highest in the green stage i.e. without preoxidation of metal, and decreased above 900 degrees C, and was the lowest in the group without paste bonder application. The difference in bond strengths was statistically highly significant for all groups. Preoxidation under vacuum before porcelain firing can effectively improve bonding. The adhesive provided with the low fusing porcelain helps in the bond between titanium & porcelain. PMID- 25134367 TI - Colour matching of composite resin cements with their corresponding try-in pastes. AB - Two shades of four resin cements (Calibra, Clearfil Esthetic, Insure, Variolink II), in light- and dual-curing modes, were tested for colour matching with their corresponding try-in pastes, immediately after photopolymerization and after 24 hour dry and dark storage. Colour measurements were performed for 0.8 mm-thick specimens through a 0.8mm-thick ceramic plate. For each resin cement, colour differences (deltaE) were calculated between the two curing modes, and between the corresponding try-in paste, at baseline and after 24h. deltaE>0 values were detected between all resin cements and their try-in pastes, which were brand/shade/curing mode depended. The try-in pastes of the Variolink II system demonstrated the best colour matching (deltaE<2). Try-in pastes of Calibra and Insure, at both curing modes, did not match at an acceptable value, the shade of their corresponding resin cements (deltaE>3.3). Calibra presented the highest colour differences. deltaE values of the Clearfil Esthetic system immediately after photo-activation ranged between 2 and 3 units. A ceramic restoration may fail aesthetically as a result of not acceptable colour match (deltaE>3.3) between the shade of certain resin cements and their relevant try-in pastes. PMID- 25134368 TI - Evaluation of Cerec endocrowns: a preliminary cohort study. AB - This study aimed to evaluate clinical qualities and evolution on ceramic endocrowns produced with the Cerec 3D (Sirona). Endocrowns were produced in a hospital environment and evaluated according to the FDI criteria on the day of placement and 6 months afterwards. Each item was graded from 1 (good) to 5 (bad). A global score, as well as a score for aesthetics, functioning and biological integration was assessed for each evaluation. During the 6-month evaluation period, the scores were always related to good clinical quality, except for single crown restoration. The scores did not change between the two periods of evaluation. PMID- 25134369 TI - The pharmaceutical symbolism of O. Henry. PMID- 25134370 TI - Deja Vu--the recycling of penicillin in post-liberation Paris. PMID- 25134371 TI - Confessions of a quasi-collector/archivist: the UCSF Robert L. Day Collection. PMID- 25134372 TI - The dispensatory of the United States of America, (2nd edition, 1834) by George B. Wood and Franklin Bache. PMID- 25134373 TI - Mahadeva Lal Schroff: father of Indian pharmacy education. PMID- 25134374 TI - Evaluation of multiplex real time polymerase chain reaction and procalcitonin in the diagnosis of sepsis. AB - BACKGROUND: Sepsis is one of the most serious and life-threatening clinical conditions of childhood. This study has been designed to evaluate how useful multiplex real-time polymerase chain reaction (PCR) is in the early diagnosis of responsible microorganisms of sepsis and to specify how serial procalcitonin level measurement is helpful to support diagnosis of sepsis. METHODS: A total of 79 blood samples from 69 consecutive patients were collected for this prospective study between 01 Sept 2009 - 29 Feb 2012. RESULTS: In the evaluation of patients who are diagnosed with sepsis out of 69 patients with 79 clinical sepsis, 24 (30.37%) had positive blood culture and 19 (24%) samples were positive for PCR. When blood culture and multiplex real-time PCR results were compared, multiplex real-time PCR had a sensitivity of 75% and specificity of 100%. When the 2 microorganisms that multiplex real-time PCR cannot detect are excluded sensitivity increased to 81.8% and specificity did not differ. Procalcitonin levels on the day sepsis is suspected had a mean level of 13.91 ng/mL (+/- 49.26), on the 1st day (after 24 hours) the mean level of procalcitonin was 15.05 ng/mL (+/- 43.95), on the 2nd day (after 48 hours) it was 14.89 ng/mL (+/- 41.57). Mean procalcitonin levels of 50 children admitted with complaints other than infection and systemic inflammation was 0.06 ng/mL (+/- 0.04). CONCLUSIONS: In conclusion, multiplex real-time PCR test would be useful in the early diagnosis of sepsis. Studying procalcitonin levels is helpful in the early diagnosis of sepsis but does not have any correlation with the isolation of microorganisms in blood culture and survival. PMID- 25134375 TI - Indirect estimation of reference intervals for thyroid parameters. AB - BACKGROUND: The aim of this work was to determine indirect reference intervals from patients' results obtained during routine laboratory work. This could be an accurate alternative to the laborious and expensive job of producing reference intervals for populations according to international recommendations. METHODS: All the results for thyrotropin (TSH), total and free thyroxine, and triiodothyronine (T4, fT4, T3, and fT3) stored in our laboratory information system between 2008 and 2011 were included in this study. We used logarithmic transformation of the raw data to exclude outliers. After visual observation of the data distribution, we estimated non-parametric reference intervals. A standard normal deviation test was performed to test the significance of differences between subgroups. RESULTS: There was no significant difference in the serum levels of the analyzed thyroid parameters, so we calculated combined reference values. However, we found a significant difference in TSH values between ambulatory and hospitalized patients, but only in 2011. Indirect reference values for TSH, T4, fT4, T3 and fT3 were 0.42 - 3.67 mIU/L, 66.0 - 136.10 nmol/L, 10.20 - 18.40 pmol/L, 1.10 - 2.39 nmol/L, and 3.17 - 5.59 pmol/L, respectively. CONCLUSIONS: The indirect determination of laboratory-specific reference intervals using patients' laboratory data is a relatively easy and inexpensive method. Also, indirect reference limits will be more precise and true if skewness and kurtosis of the distribution are not too large. PMID- 25134377 TI - Hemoglobin Q-Thailand and its combinations with other forms of thalassemia or hemoglobinopathies in northern Thailand. AB - BACKGROUND: There have been no reports for the frequency of Hb Q-Thailand [alpha 74(EF3)Asp --> His, GAC > CAC] and its combinations either with other forms of thalassemia or hemoglobinopathies in Northern Thailand. The aims of this study were to search for Hb Q-Thailand and its combinations in Northern Thai population and to analyze fractions of hemoglobin in Hb Q-Thailand and its combinations on high performance liquid chromatography (HPLC) chromatograms and/or capillary electrophoresis (CE) electrophoregrams. METHODS: Blood samples from public and private hospitals in 7 northern provinces of Thailand were analyzed for thalassemia and hemoglobinopathy diagnoses using HPLC and/or CE and DNA analysis techniques at the Thalassemia Laboratory, Associated Medical Sciences Clinical Service Center, Chiang Mai, Thailand. RESULTS: Hb Q-Thailand was found in 13 of 13,596 (0.10%) samples; 6 were heterozygous Hb Q-Thailand, 4 were compound Hb Q Thailand/alpha-thalassemia-1 Southeast Asian (SEA) type deletion and 3 with combinations of Hb Q-Thailand/beta(0)-thalassemia, Hb Q-Thailand/Hb E and Hb Q Thailand/Hb E/alpha-thalassemia-1 SEA type deletion. The fractions of hemoglobin on HPLC chromatograms and CE electrophoregrams were observed based on types of combinations. CONCLUSIONS: Hb Q-Thailand and its combinations could be found in northern Thai population with the frequency of 0.10%. Thus, the better understanding of HPLC chromatogram and/or CE electrophoregram patterns of Hb Q Thailand and its combination is essential for diagnosis and genetic counseling of thalassemia and hemoglobinopathies in this area. PMID- 25134376 TI - The evaluation of serum surfactant protein D (SP-D) levels as a biomarker of lung injury in tuberculosis and different lung diseases. AB - BACKGROUND: To evaluate the predictive powers of serum surfactant protein D (SP D) levels as a biomarker of lung damage in tuberculosis and lung diseases. METHODS: This study prospectively included 137 subjects who applied to our hospital. We measured serum SP-D levels from patients with active tuberculosis (TB) (n = 35), chronic obstructive disease (COPD) patients experiencing acute exacerbations (n = 30), patients with pneumonia (n = 45), and control subjects (n = 27). RESULTS: The mean age of all patients was 54.89 +/- 18.81 years (15 to 100 years); males accounted for two-thirds (70.1%) of the cases. Serum SP-D levels were higher in patients with pnemonia, tuberculosis, and COPD than in control patients (p < 0.001, p < 0.001, and p < 0.001, respectively). Serum SP-D levels in patients with pneumonia, tuberculosis, and COPD were higher than in the control group and mean serum SP-D levels were associated with pulmonary injury scores in patients with pneumonia, severity of COPD attack, and the extent of radiological lung involvement in patients with pneumonia and TB. CONCLUSIONS: Serum SP-D may be a useful biomarker of the severity of pneumonia, COPD, and tuberculosis. PMID- 25134378 TI - Serum procalcitonin in cirrhotic patients with septic shock: relationship with adrenal insufficiency and clinical outcomes. AB - BACKGROUND: Serum procalcitonin is commonly used to differentiate systemic inflammation due to infection from non-infectious causes. Limited data exist on the value of procalcitonin in predicting relative adrenal insufficiency (RAI). This study evaluated the value of procalcitonin in predicting RAI and mortality in cirrhotic patients with septic shock. METHODS: This was a post-hoc analysis of a randomized placebo-controlled trial that evaluated low-dose hydrocortisone in cirrhotic patients with septic shock. Extracted first study-day data included serum procalcitonin, baseline serum cortisol, cortisol level after 250 microg - adrenocorticotropic hormone stimulation test and 28 - day mortality. RAI was defined as a baseline serum cortisol < 10 microg/dL or cortisol not rising by > 9 microg/dL after stimulation. Procalcitonin > 0.5 ng/mL was considered high. RESULTS: Forty-five patients had serum procalcitonin measured (mean = 2.7 +/- 3.2 ng/mL, first and third quartiles were 0.3 and 3.3 ng/mL, respectively). Most (78%) patients had high procalcitonin levels. RAI was present in 34 (76%) patients. Patients with high procalcitonin were more likely to have RAI (odds ratio, 4.8; 95% confidence interval, 1.1 - 22.1). Receiver operator characteristic curve analysis showed that the best cut-off for detecting RAI was 1.0 ng/mL (sensitivity = 79% and specificity = 55%). High serum procalcitonin was not associated with 28 -day mortality (80% for normal procalcitonin and 77% for high procalcitonin, p = 0.61). CONCLUSIONS: High serum procalcitonin was highly associated with RAI in cirrhotic patients with septic shock. Procalcitonin was not associated with 28 - day mortality in this patient population. PMID- 25134379 TI - Biochemical evaluation of hyaluronic acid in breast cancer. AB - BACKGROUND: The latest experimental studies on human cancer diseases have observed the bioactive role of hyaluronic acid (HA) during carcinogenesis. HA is a component of the extra-cellular matrix (ECM). It is closely correlated with tumor cell growth, proliferation, and metastasis. The present study aimed to evaluate the biochemical role of HA and its degrading enzymes and products in breast cancer (BC) patients under therapy treatment. METHODS: An ELISA method was used to determine HA levels and standard spectrophotometric techniques were used to estimate the activities of HA degrading enzymes hyaluronidase (HAS), N-acetyl beta-D-glucosminidase (NAG), and beta-glucuronidase (beta-Glu) and the concentration of both glucoseamine (G-Amine) and glucuronic acid (GA) as degrading products in blood sera of 50 BC patients before and after chemotherapy treatment and in blood sera of 40 healthy women as controls. Statistical analyses were performed by a statistical package for social sciences (SPSS, version 15.0). RESULTS: Elevated serum HA levels, increased HAS, NAG, and beta-Glu activities and high concentrations of G-Amine and GA were significantly found (p < 0.001) in patients before treatment compared to controls. After all BC patients had received the first chemotherapy course, HA and its previous degrading parameters were significantly decreased (p < 0.001) in post-treated patients compared to pre treated patients. CONCLUSIONS: Hyaluronic acid and its degrading enzymes and products can be considered a biomarker for early detection of recurrent disease and also for monitoring the effective therapeutic follow up of BC patients. PMID- 25134381 TI - The endothelial protective effects of pioglitazone on insulin resistance in endothelial cells. AB - BACKGROUND: Insulin resistance plays an important role in vascular endothelial damage and atherosclerosis. Pioglitazone is an insulin-sensitizing agent and can reduce insulin resistance. METHODS: In this study, the cellular model of insulin resistance was used to investigate the mechanisms involved in the endothelial protective effects of pioglitazone in a vascular endothelial cell damage model. RESULTS: The results showed that pioglitazone could effectively increase the survival rate of human umbilical vein endothelial cells (ECV), reduce apoptosis, and relieve insulin resistance damage. To understand the endothelial protective effect mechanisms of pioglitazone, we showed that 50 ng/mL and 100 ng/mL of pioglitazone could upregulate the levels of inducible nitric oxide synthase (NOS) and pioglitazone could induce NO levels. CONCLUSIONS: These results suggested that pioglitazone could have endothelial protective effects in a vascular endothelial cell damage model of insulin resistance and used to prevent beforehand and treat a vascular endothelial cell damage of insulin resistance. PMID- 25134380 TI - Establishing reference values for blood urea nitrogen and serum creatinine in Chinese Han ethnic adult men. AB - BACKGROUND: The aim was to calculate the two-sided 95th percentile reference values for blood urea nitrogen (BUN) and serum creatinine (SCr) in Chinese Han ethnic adult men. METHODS: Serum samples were collected from Chinese Han ethnic adult men aged 20 - 69 years. After screening based on the inclusion and exclusion criteria, a total of 1575 individuals were enrolled in our study. BUN and SCr values were measured on an automatic analyzer (Dade Behring, USA). The data was analyzed and calculated using nonparametric statistical methods. RESULTS: BUN and SCr values were not normally distributed. The reference values were in the range 3.3 - 7.5 mmol/L for BUN and 64 - 113 micromol/L for SCr. BUN levels were significantly lower in the smoking group than the non-smoking group (Z = -4.52, p < 10(-5)). An increase with age was observed in BUN levels (r(s) = 0.172, p < 0(-5)) and lower SCr levels were weakly associated with the older subjects (r(s) = -0.071, p = 0.005). Moreover, it was found that higher Body Mass Index (BMI) tended toward higher levels of SCr (r(s) = 0.118, p < 10(-5)). CONCLUSIONS: The reference values established for BUN and SCr exhibit a slight deviation compared to those developed in previous studies. We propose reference values of BUN for smokers and non-smokers be constructed, and age- and BMI specific reference values be applied in clinical laboratories. PMID- 25134382 TI - Determination of reference values for serum folate and vitamin B12 using three different immunoassays: is it worth making an effort to produce them in our laboratory? AB - BACKGROUND: Despite being a widely studied concept, the reference interval is the most widely used medical decision-making tool. As such, it is vital that these limits are correctly established and regularly reviewed in the clinical laboratory. METHODS: The reference population comprised 315 healthy individuals selected a priori from Bizkaia province. Blood and serum samples were sent for subsequent assay of vitamin B12 and folate using three immunochemical methods. Reference values were calculated using non-parametric methods. RESULTS: The reference values for serum vitamin B12 and folate were almost identical to those obtained previously using the same methods. Use of new reference values led to an increase in the kappa value despite the low agreement in the case of vitamin B12 (0.4 - 0.62). However, precision obtained for vitamin B12 (94.48 - 96.55%) and folate (95.77 - 97.18%) was very high. The intraclass correlation coefficient ranged from 0.723 to 0.894. Furthermore, a Passing-Bablok regression analysis gave acceptable correlation coefficients of 0.75 - 0.94 for vitamin B12 and 0.92 0.95 for folate. CONCLUSIONS: Vitamin B12 and folate deficiencies are currently being over-diagnosed leading to an increase in the number of unnecessary consultations. The main conclusion that can be drawn from our study has resulted in a change in reference values in our laboratory, with a subsequent increase in our ability to accurately detect possible deficiencies. Furthermore, as this study involved all methods currently in use in the Basque healthcare network, its conclusions can be extrapolated to the whole population covered by Osakidetza, thereby improving the rational use of healthcare funding. PMID- 25134383 TI - Clinicopathological and prognostic significance of serum cytokine levels in breast cancer. AB - BACKGROUND: This study was designed to examine the serum levels of six cytokines (IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, and IL-10) in treated and untreated breast cancer patients and assess their clinical significance. The correlation of the Th1/Th2 type cytokine levels and the clinicopathologic variables was further evaluated. METHODS: Cytometric Bead Array (CBA) was used to examine the levels of Th1 cytokines (TNF-alpha, IFN-gamma, and IL-2) and Th2 cytokines (IL-4, IL-5, and IL-10) in serum of 36 untreated and 73 treated breast cancer patients and 51 healthy females as control. RESULTS: In the untreated group, the levels of IFN gamma, IL-4 and IL-5 were significantly higher than in control group (p < 0.05). IFN-gamma, IL-2, IL-5, and IL-10 levels were higher in treated group than in untreated group (p < 0.05); IFN-gamma/IL-4 ratio of the treated group was higher than the untreated group (p < 0.05). Meanwhile, the cytokine levels were significantly different in different pTNM stages and lymph node involvement groups. Survival analysis revealed that the IFN-gamma/IL-4 ratio, pTNM stage, and lymph node involvement affected the survival of breast cancer patients. The pTNM stage was an independent significant prognostic factor. CONCLUSIONS: Breast cancer patients presented a Th1/Th2 imbalance and immune function disorder, which correlated with pTNM stage and lymph node involvement. Higher IFN-gamma/IL-4 ratio predicted a favorable outcome in breast cancer patients. PMID- 25134384 TI - Proposed guidance for carryover studies, based on elementary equivalence testing techniques. AB - BACKGROUND: Carryover experiments are widely used for clinical chemistry and immunochemistry analysers to evaluate and validate carryover effects. The experimental design is well described. However, there is no guideline on the statistical approach on data analysis, especially if absence of carryover has to be shown. The only reporting of carryover in ppm is not helpful because its uncertainty is not taken into account. Furthermore, the most commonly used method fails to demonstrate the absence of carryover. We propose a step-by-step guidance applying a new statistical design for analysis of carryover studies based on equivalence testing, and provide a sample based tutorial. METHODS: For statistical analysis of carryover effects an one-sided version of equivalence testing by comparing the difference with a predefined limit (i.e., a test of non superiority) is used. The methodology is demonstrated by measuring total betahCG in human serum samples with a UniCel DxI 880 analyser. RESULTS: A new statistical approach based on equivalence testing has been developed for analysis of data resulting from a typical experimental protocol for carryover studies. Experiments using 8 (11) cycles of high and low concentration samples are appropriate to validate the absence of carryover with 80% (90%) power and an alpha-level of 0,05 if no carryover is expected. We propose to predefine an acceptance criterion based on the imprecision (here: expressed as one standard deviation) observed for those replicates of the low concentration samples expected to be unaffected by carryover. In the demonstration, the absence of carry-over was concluded with a significance of p < 0.05. CONCLUSIONS: Appropriate statistical methods should be applied when the target of a method-validation experiment is (i) absence of any effect, (ii) non-inferiority/non-superiority or (iii) equivalence. Using the example of carryover studies, we show that one-sided equivalence testing is the proper model, and propose a guidance for analysis of these experiments. The example of carryover illustrates a methodology which is also applicable for analysis of a wide range of experimental approaches, including method comparison, commutability and robustness. PMID- 25134385 TI - Transforming growth factor beta 1 as a risk factor for cardiovascular diseases in end-stage renal disease patients treated with peritoneal dialysis. AB - BACKGROUND: The aim of the study was to evaluate the relationship between the atherosclerotic changes in the carotid arteries expressed as common carotid artery intima-media thickness (CCA-IMT) with Body Mass Index (BMI), serum lipid levels, and selected inflammatory state markers in peritoneal dialysis (PD) patients. METHODS: The study included 67 patients (31 female and 36 male) on PD therapy for 30.4 +/- 24.2 months. Average age of the patients was 52.9 +/- 12.5 years (ranged from 19 to 75 years). The measurement of the CCA-IMT was performed by ultrasonography evaluation. BMI was calculated using the Quetelet formula. Serum lipid levels and hsCRP were performed using routine methods. IL-6, TGF beta1, TNF-alpha, and hepatic growth factor (HGF) were tested with ELISA assays. RESULTS: In univariate analysis, the strongest factor influencing CCA-IMT was age (R = 0.54; p < 0.0001). CCA-IMT correlated positively with BMI (R = 0.39; p = 0.003). Of the inflammatory markers studied, significant correlations with CCA IMT were shown for IL-6 (R = 0.35; p = 0.009), and TGF-beta (R = 0.31; p = 0.02). In multiple regression, only In TGF-beta1 (partial correlation coefficient = 0.29; p = 0.04) appeared to predict CCA-IMT independently of age and BMI, while IL-6 was not significant in the analysis. The regression model including age, BMI and TGF-beta1 as independent variables, explained 43% of CCA-IMT variance. Again, age was the strongest predictor of CCA-IMT (partial correlation coefficient = 0.50). CONCLUSIONS: Increased concentration of TGF-beta1 may be a biomarker of the development of cardiovascular diseases in patients treated with PD, as well as a prognostic factor in the evaluation of atherosclerosis progression in this group of patients. PMID- 25134386 TI - Genetic instability in patients with pancreatic cancer analyzed by SCARs and electrochemical sensors. AB - BACKGROUND: Pancreatic cancer is an aggressive disease and the fourth most common cause of cancer death across the globe. It is often not diagnosed until it is advanced. It is necessary to establish a new technology to detect DNA instabilities during the progression of pancreatic cancer and to screen for new molecular markers coupled to putative unknown oncogenes. METHODS: A total of 25 pancreatic cancer tissue specimens were analyzed by sequence-characterized amplified regions (SCARs), including two pathological types (pancreatic ductal adenocarcinoma and neuroendocrine carcinoma). There were 41 random primers and eight long fragment primers used for PCR amplification, and the difference of dNTPs consumptions were detected by nano-electrochemical sensors. Once both dATP and dGTP are significantly different in oxidation current (reduce or increase simultaneously), separate the different genes by electrophoresis, then clone and sequence the genes, and carry out homology analysis. RESULTS: Both dGTP and dATP showed good oxidation behavior on the carbon nanotube modified glassy carbon electrode. There were 32 different fragments in malignant tissues compared with normal control, among them a SNP located in 5'UTR of the leucine zipper protein 4 gene which is significantly correlated with pancreatic cancer (OR = 9.50) and it was confirmed by direct sequencing. CONCLUSIONS: SCARs combined with the nanoelectrochemical sensor can be used for screening genetic instabilities in pancreatic cancer, and leucine zipper protein 4 was a novel pancreatic cancer related gene. PMID- 25134387 TI - Reference interval for osteocalcin in Chinese Han ethnic males from the Fangchenggang Area Male Health and Examination Survey. AB - BACKGROUND: The aim of this study was to set a reference interval (RI) for osteocalcin (OC) in a healthy Han male population from the Fangchenggang Area Male Health and Examination Survey (FAMHES) project and study the effects of age, BMI, smoking, and alcohol consumption. METHODS: We used data from 2018 Han ethnic males who participated in FAMHES project from September 2009 to December 2009. Serum OC values were measured by electrochemiluminescence immunoassay on COBAS 6000 system E601 (Elecsys module) immunoassay analyzers. RESULTS: OC data does not have a normal distribution or Gaussian pattern (Z = 3.791, p < 0.001). After log-transformation, data took on a normal, Gaussian distribution (Z = 0.968, p = 0.306). The RI of serum OC was 12.49 - 43.94 ng/mL. No difference in OC concentration was noted either between non-smoker or smoker groups (p = 0.629) or non-drinker and drinker groups (p = 0.748). OC levels varied with age (r = 0.371, p < 0.001) and BMI (r = -0.331, p < 0.001), and the age-dependent and BMI dependent RIs were calculated. CONCLUSIONS: The RIs for serum OC exhibit slight differences compared to previously reported reference ranges. Age-dependent and BMI-dependent RIs for serum OC should be implemented in clinical laboratories. PMID- 25134388 TI - The diagnosis of high altitude illness by the determination of plasma dermcidin isoform 2 levels by enzyme linked immunosorbent assay. AB - BACKGROUND: High altitude illness (HAI) is a cluster of syndromes which develops due to the injury of the central nervous system produced by the reduction of the partial pressure of O2 in the atmosphere which disappears on decent. The HAI also results in a prothrombotic condition leading to acute coronary syndrome (ACS), which cannot be controlled on descent to the ground level. There is no diagnosis in HAI to forewarn of the impending ACS. A protein identified to be dermcidin isoform 2 (dermcidin), produced in the system due to environmental stresses, has been reported to be a potent diabetogenic agent. Investigation was carried out to determine the systemic stimulation of dermcidin synthesis at different levels of altitudes in normal adult male volunteers to assess the feasibility of developing a diagnosis for ACS in HAI due to dermcidin synthesis. METHODS: Normal, nondiabetic, normotensive male volunteers (25 - 35 years old, n = 16) participated in the study. The plasma dermcidin level was determined by enzyme linked immunosorbent assay (ELISA) and by in vitro translation of dermcidin mRNA. The plasma insulin level was determined by ELISA and blood glucose level was determined in a glucometer (Behringer). RESULTS: The plasma dermcidin level in the volunteers at ground level was 10 +/- 2.10 nM and increased to 80 +/- 4.62 nM at 15000 feet altitude. For each 1000 feet increase of altitude, the dermcidin level increased by 5.83 +/- 0.21 nM with a Coefficient of Correlation "r" = +0.9405. The increase of plasma dermcidin level was found to be inversely related to the decrease of plasma insulin level from 23 microunit/mL to 5 microunit/mL from sea level to 15000 feet height ("r" = -0.9951) with concomitant increase of blood sugar level from 80 +/- 3.6 mg/dL to 135 +/- 2.01 mg/dL. CONCLUSIONS: These results suggest the feasibility of a diagnosis of a prediabetic condition by determining the plasma dermcidin level in HAI by simple ELISA which may also be useful to forewarn of the possibility of developing an impending prothrombotic condition in HAI. PMID- 25134389 TI - Mean platelet volume (MPV) may simply predict the severity of sepsis in preterm infants. AB - BACKGROUND: To evaluate the efficacy of serial mean platelet volume (MPV) measurements in diagnosis and followup of sepsis and to compare its effectiveness with C-reactive protein (CRP) and interleukin-6 (IL-6) in sepsis. METHODS: Preterm infants, whose gestational age and weight were matched to each other, were grouped as control (n = 100) and sepsis (n = 91). Platelet indices (MPV, PDW, platelet count), CRP, and IL-6 levels were measured for the control group and on the day of diagnosis (1st day), 3rd, and 7th days of the sepsis group. RESULTS: There were significant differences between the control and sepsis group in terms of platelet count and MPV/PDW levels (p < 0.05). No significant changes were found in either platelet count or MPV and PDW of infants between early and late onset sepsis, nor between culture proven and non proven sepsis, nor among different infectious agents (gram positive/negative and fungal infections) (p > 0.05). Additionally, non-survivors with sepsis had higher levels of MPV and PDW during sepsis episodes on consecutive days (p < 0.05), in contrast to lower platelet counts in non-survivors (p < 0.05). Moreover, a positive correlation was found between MPV and IL-6 and CRP. A MPV value of 10.35 fL was identified as the cut off value in patients probably resulting in sepsis with a sensitivity of 97.8% and specificity of 78.7% (AUC = 0.949; p < 0.001), and a MPV value of 10.75 fL was determined as the cut off value in patients possibly resulting in death at diagnosis with a sensitivity of 95.2% and a specificity of 84.9% (AUC = 0.944; p < 0.001). CONCLUSIONS: The mean platelet volume can be used in addition to CRP and IL-6 at both diagnosis and follow-up of sepsis and the response of antimicrobial treatment. PMID- 25134390 TI - Serum lipid profile in female patients with severe acne vulgaris. AB - BACKGROUND: Acne vulgaris is one of the most common skin conditions affecting young adults. The relationship between lipid profile or lipid ratios and acne is not widely reported. METHODS: A case control study was performed in 90 females with severe acne vulgaris. Lipid profiles were measured, lipid ratios were calculated, and results were compared with 90 age matched healthy controls. RESULTS: Total cholesterol, LDL-C, HDL-C, Apo A1, though, were significantly higher in patients as compared to healthy controls but all the levels in patients were within normal range so we calculated lipid ratios for TC/HDL, LDL/HDL, TG/HDL, Apo B/Apo A1, Atherogenic index of plasma and found that all the ratios were significantly higher as compared to controls using a t-test. The area under receiver operating characteristic curve was > 0.7 for all the lipid ratios and sensitivity and specificity were calculated for all the ratios and it was highest for Apo A1/Apo B. CONCLUSIONS: We suggest using lipid ratios as a screening test in females with acne vulgaris to diagnose dyslipidemia at an early stage but further studies are required to see the effect of treating hyperlipidemia in females with severe acne vulgaris. PMID- 25134391 TI - Von Willebrand factor multimer structure is neither acutely nor chronically affected by plateletpheresis. AB - BACKGROUND: Plateletpheresis (PltPh) exposes the donor's blood to artificial surfaces and mechanical forces such as shear stress and centrifugation. In terms of the donor's safety and the quality of the apheresis platelet concentrate (APC), possible impairment of platelet function due to PltPh should be excluded. Von Willebrand factor (VWF) plays a pivotal role in platelet adhesion and aggregation. VWF is a multimeric protein and can be damaged by adsorption or shear stresses. It is unclear whether VWF structure could be damaged during PltPh, leading to platelet dysfunction. METHODS: We analyzed VWF antigen (VWF:Ag), ristocetin cofactor (VWF:RCo), and VWF multimer structure immediately before and after apheresis in the donor and in the APC. These parameters and factor VIII activity (FVIII:C) and closure time using PFA-100 (CT) were also analyzed in blood samples taken from new donors before the first and before subsequent donations and from long-term donors. RESULTS: During apheresis, VWF:Ag falls by about 15% but the VWF multimer structure remains unchanged. In samples taken before subsequent donations, there was a tendency of VWF:Ag and FVIII:C to increase throughout the initial donations, but no alteration of multimer structure. Long-term donors, however, show a normal VWF multimer structure and normal concentrations of VWF:Ag, VWF:RCo, and FVIII:C. In some donors with low normal VWF:Ag and VWF:RCo, PFA-100 CT was prolonged. CONCLUSIONS: VWF multimer structure is neither acutely nor chronically affected by plateletpheresis. A decrease in VWF:Ag with no functional damage only occurs acutely and can be explained by the withdrawal of plasma and dilution with the anticoagulant ACD-A due to apheresis. PMID- 25134392 TI - Evaluation of a chromogenic medium for detection of extended-spectrum-beta lactamase-producing Escherichia coli and Klebsiella pneumoniae strains. AB - BACKGROUND: Because of the emergence and spread of extended-spectrum-beta lactamase (ESBL)-producing strains which are resistant to many antibiotics, reliable detection of ESBL is very important for infection control. Several chromogenic media have been proposed for the detection of ESBL producers in addition to the conventional phenotypic and genotyping methods. The aim of the present study was to evaluate the performance of Brilliance ESBL agar (Oxoid; Thermo Fisher Scientific, UK), a selective chromogenic agar for the detection of ESBL-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) strains. METHODS: A total of 237 strains (143 ESBL producers (76 isolates of E. coli and 67 isolates of K. pneumoniae) and 94 non-ESBL producers (44 isolates of E. coli and 50 isolates of K. pneumoniae)) isolated from various clinical specimens were included in the study. Isolates were identified by conventional methods, Phoenix system (Becton Dickinson, USA), and mass spectrometry. ESBL confirmation was performed by phenotypical tests. A 10 microL aliquot of each isolate's 0.5 McFarland suspension was streaked onto Brilliance ESBL agar. All plates were incubated at 37 degrees C for 24 hours and then were interpreted for growth and colony color according to the manufacturer's recommendations. Identification and ESBL test results were used to calculate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the medium evaluated at 24 hours. RESULTS: The sensitivity, specificity, PPV, and NPV of the medium were 97.9%, 100%, 100%, and 96.9%, respectively, when considering only species specific colored colonies of the isolates. CONCLUSIONS: Brilliance ESBL agar could provide a practical alternative to the traditional methods for the identification of ESBL producers. PMID- 25134393 TI - Utility of multiple-locus variant-repeat analysis method for the outbreak of the Pseudomonas aeruginosa isolates. AB - BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) predominated in hospitals. METHODS: In order to determine the source of the outbreak and take effective measures to prevent the spread, we tested their relationships between the strains. 97 P. aeruginosa samples were analyzed by multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) method. In order to identify a minimal subset that could provide high discrimination, we evaluated the ability of various VNTR sets. RESULTS: The result showed all of the 11 loci displayed high discrimination, and the lowest loci was ms223 (h = 0.59). The 97 strains were all discriminated (HGDI = 1.0000). The top 7-locus set produced a HGDI value of 1.0000, which was the same as the 11-locus set. The 4-locus set had a HGDI value of 0.9972 with a clustering rate of 11.3%. The strains were divided into four groups based on the phylogenetic clustering and genotypic characteristics. There were obvious differences among the four groups regarding the drug-resistance patterns of Imipenem, Ciprofloxacin, Ceftazidime, Levofloxacin, Meropenem, Piperacillin, Cefepime, Aztreonam (p < 0.05). CONCLUSIONS: In conclusion, the transmission of the strains was not found in this study. The 7-locus set yielded a high discrimination, while for an easier and more robust MLVA scheme, the number of markers can be reduced to 4 loci of ms212, ms211, ms213, and ms142. These four strains from four inpatients in the same ward displayed the same drug resistance spectrum. The MLVA genotype results showed the four strains had the same gene structures. The four patients were from the same treatment group. They showed the IMP-1 allele and belonged to the aac (6')-I type, and there was a deletion of the OprD2 gene in four strains, supporting the MLVA results in suggesting that they are similar. PMID- 25134394 TI - The role of Porphyromonas gingivalis in the development of atherosclerosis and its relationship with fim A genotype. AB - BACKGROUND: Porphyromonas gingivalis, a major periodontal pathogen, is gaining increasing attention for its possible association with atherosclerosis. Its fimbriae are classified into six genotypes (Types I-V, Ib) based on the diversity of the fim A genes encoding the fimbrial subunits. In this study, fim A genotype's distribution of P. gingivalis was analyzed in atherosclerotic plaque specimens. METHODS: A total of 50 atherosclerotic plaque specimens and 50 non atherosclerotic, post stenotic aneurysm specimens were collected from patients undergoing cardiovascular surgery. Bacterial DNA was also extracted from each specimen, as real-time PCR was carried out with P. gingivalis-specific primer sets. The positive specimens of P. gingivalis were further analyzed to discriminate the fim A genotype using real-time and nested PCR methods. RESULTS: P. gingivalis was detected only in one atherosclerotic plaque; however, the genotype was nontypable in this specimen. CONCLUSIONS: We state that it is not easy to show a significant relationship between P. gingivalis, its fim A genotype, and atherosclerosis. We suggest that new extended studies based especially upon the quantitave determination of P. gingivalis and its genotype distribution on atherosclerotic specimens are needed to show an evident relationship between atherosclerosis and P. gingivalis. PMID- 25134395 TI - Masked monoclonal gammopathy in capillary electrophoresis. AB - BACKGROUND: Although the method of choice to detect M-protein is electrophoresis on an agarose gel, such gel electrophoresis (GE) is labor-intensive, time consuming, and not standardized. In contrast to GE, capillary electrophoresis (CE) has some merits because it is automated, fast, and highly reproducible. However, CE results occasionally make the interpretation difficult and require additional confirmatory tests like GE. METHODS: In order to assist a correct reporting of CE results and compatible interpretations between two different electrophoresis methods, we report here two unusual cases of monoclonal gammopathy by a pattern of polyclonal gammopathy upon CE interpretation in patients with end stage renal disease and multiple myeloma. RESULTS: In these cases, serum CE showed the broad bumpy peak in the gamma region. This bumpy peak does not drop completely flat after the reaction with anti-FLC. CONCLUSIONS: Because the plasma cell is a B-cell lineage and plays an important role in adaptive immunity, MG accompanying with PG is not rarely found in plasma cell dyscrasia. If the broad bumpy peak is observed in CE, careful examinations must be done to rule out the hidden M-peak. In our cases, a parallel use of gel-based methods was very helpful as it revealed monoclonal bands. PMID- 25134396 TI - Serum soluble CD200 level was higher in patients with bullous pemphigoid during the active phase of the disease than for healthy individuals. AB - BACKGROUND: CD200 is a novel immunosuppressive molecule, existing both as cell membrane bound and as a soluble form in serum (sCD200), which acts to regulate inflammatory and acquired immune responses. Recently, our study group showed that sCD200 was found in serum and blister fluid in a patient with bullous pemphigoid and that anti-IgE therapy impacted those levels. We therefore planned this study to evaluate the soluble serum CD200 levels of bullous pemphigoid patients and compare it with that of healthy controls. We also analysed the association between the sCD200 levels and the clinical severity of the disease in bullous pemphigoid patients. METHODS: We investigated 5 consecutive patients with bullous pemphigoid, and 15 healthy controls were included in this study. Assessment of clinical examination and measurement of laboratory investigation were performed on the same day. Bullous pemphigoid patients were also assessed for Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Concentrations of anti-BP180 and soluble CD200 in the serum samples were quantified using ELISA kits. RESULTS: The serum soluble CD200 level was observed to be statistically significantly higher in patients with BP (77.6 +/- 15.7 pg/mL) compared with healthy controls (26.1 +/ 6.7 pg/mL), (p < 0.001). Nevertheless, there was no statistically significant correlation between serum soluble CD200 levels and clinical severity scores and Anti-BP180 values (p = 0.402, p = 0.395, respectively). However, there was a statistically significant correlation between ABSIS and Anti-BP180 levels in patients with BP (p = 0.036). CONCLUSIONS: CD200 might play a role in the immune response in the pathogenesis of bullous pemphigoid. However, we do not know the exact mechanism of CD200 in the disease initiation and/or progression. PMID- 25134397 TI - Patients infected with avian influenza A H7N9 virus have abnormally low thyroid hormone levels. AB - BACKGROUND: In March 2013, the novel avian influenza A H7N9 virus spread throughout China. This study evaluated whether thyroid function was altered in patients infected with H7N9 virus. METHODS: We analyzed thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total tetraiodothyronine (TT4), free triiodothyronine (FT3), and free tetraiodothyronine (FT4) levels in 17 patients infected with H7N9 on admission to our hospital and compared the values to the reference ranges for these thyroid hormones. RESULTS: Of the 17 patients, 12 (70.6%) patients had abnormally low TT3 levels, 10 (58.8%) patients had abnormally low FT3 and TSH levels, and 5 (29.4%) patients had abnormally low TT4 and FT4 levels (below the lower limit of the reference ranges for each hormone). CONCLUSIONS: Abnormally low thyroid hormone levels was common in patients infected with H7N9. PMID- 25134398 TI - Free light chain levels in pediatric patients with inflammatory conditions. AB - BACKGROUND: Because free light chain assays measure polyclonal as well as monoclonal free light chain components, some previous studies focused on the potential utility of the free light chain assay for detecting chronic immune stimulation, which occurs in autoimmune diseases and allergies. However, most of these trials have been limited to adult patients. In this study, we evaluated the paired serum and urinary free light chain levels of pediatric patients with various inflammatory conditions to investigate the clinical significance of free light chain measurement in pediatrics. METHODS: The study included 227 paired serum and urine specimens from 134 pediatric patients at our hospital between January and February of 2012. Serum and urinary FLC levels were measured using a Freelight Kit (The Binding Site, Ltd., Birmingham, UK). RESULTS: The serum lambda and urine kappa and lambda components were significantly increased only in the renal impairment group, not in the mild inflammatory group. FLC ratios were not significantly different among these groups. CONCLUSIONS: In serum, only the L components were significantly increased. This result may indicate the presence of a dimeric L structure, in contrast with monomeric K. FLC levels might also be influenced by renal conditions other than mild inflammation. Therefore, as shown in previous studies of adult patients, renal reference ranges might be needed to interpret FLC results, especially for dimeric L components. PMID- 25134400 TI - Auto-enroll rule may avert Obamacare turmoil in November. PMID- 25134401 TI - High court ruling forcing NLRB to reopen cases has hospitals wary. PMID- 25134402 TI - Hospitals Houston's energy boom fuels hospital rush to burbs. PMID- 25134403 TI - Health spending shrinks, may surge next year. PMID- 25134404 TI - Community health centers face major funding loss. PMID- 25134405 TI - HFMA homes in on 'dollars and sense' consumer era. PMID- 25134406 TI - EHR leaders vying for $11 B military contract. PMID- 25134407 TI - CME shelter. Sunshine Act waiver for med ed payments may prompt marketing shift for product makers. PMID- 25134408 TI - Warning label limbo. FDA rule letting generic-drug makers update risk alerts draws heavy flak. PMID- 25134409 TI - Insuring against the future. PMID- 25134410 TI - Collaboration, not vertical integration, offers best chance for success. PMID- 25134411 TI - Doctors should be captain of the ship. PMID- 25134412 TI - Improving women's health with no guarantee of getting paid. PMID- 25134413 TI - New lipophilic polyelectrolyte gels containing quaternary ammonium salt with superabsorbent capacity for organic solvents. AB - Water and soil pollution by organic pollutants from petrochemical plants has become one of the major environmental problems in recent years. Lipophilic polyelectrolyte gels with ionic groups dissociable in nonpolar organic solvents show an enhanced swelling ability in a corresponding media attributed to the electrostatic repulsion and osmotic pressure provided by dissociated ionic groups. Here, we synthesized new lipophilic polyelectrolyte gels based on an easily available electrolyte monomer, methacryloxyethyl dimethyloctane ammonium trifluoromethanesulfonimide (MODAT), and a lipophilic neutral monomer, dodecyl acrylate by radiation-induced polymerization and cross-linking. The resultant lipophilic polyelectrolyte gels could absorb plenty of organic solvents with dielectric constants lower than 20 and exhibited a high absorbing ability at a wide range of temperatures (0-40 degrees C). The maximum swelling degree could reach as high as 200 g/g in some media, such as 1,2-dichloroethane (199.4 g/g) and dichloromethane (204 g/g), which was much higher than that of the nonionic gel without the addition of MODAT. Moreover, the resultant lipophilic polyelectrolyte gels could release most of the absorbed solvents within several hours and then be reused. It is expected that this new type of lipophilic polyelectrolyte gels may be a suitable candidate as organic pollutant absorbents. PMID- 25134414 TI - Assessing the quality of care in a new nation: South Sudan's first national health facility assessment. AB - OBJECTIVES: We adapted a rapid quality of care monitoring method to a fragile state with two aims: to assess the delivery of child health services in South Sudan at the time of independence and to strengthen local capacity to perform regular rapid health facility assessments. METHODS: Using a two-stage lot quality assurance sampling (LQAS) design, we conducted a national cross-sectional survey among 156 randomly selected health facilities in 10 states. In each of these facilities, we obtained information on a range of access, input, process and performance indicators during structured interviews and observations. RESULTS: Quality of care was poor with all states failing to achieve the 80% target for 14 of 19 indicators. For example, only 12% of facilities were classified as acceptable for their adequate utilisation by the population for sick-child consultations, 16% for staffing, 3% for having infection control supplies available and 0% for having all child care guidelines. Health worker performance was categorised as acceptable in only 6% of cases related to sick-child assessments, 38% related to medical treatment for the given diagnosis and 33% related to patient counselling on how to administer the prescribed drugs. Best performance was recorded for availability of in-service training and supervision, for seven and ten states, respectively. CONCLUSIONS: Despite ongoing instability, the Ministry of Health developed capacity to use LQAS for measuring quality of care nationally and state-by-state, which will support efficient and equitable resource allocation. Overall, our data revealed a desperate need for improving the quality of care in all states. PMID- 25134415 TI - Retrospective cohort study of 4591 Straumann implants in private practice setting, with up to 10-year follow-up. Part 1: multivariate survival analysis. AB - OBJECTIVE: The purpose of this retrospective, noninterventional, open cohort study is to report on the long-term survival of dental implants, in private practice representing the daily realities of implant treatment. The data are analyzed to discern statistical relationships between explanatory variables and implant failure. MATERIALS AND METHODS: A total of 4591 Straumann implants were placed in 2060 patients between 1999 and 2012. Patients were evaluated after 2-3 months, 1, 3, 5, and 7 years and, in some cases, up to 10 years. The cumulative survival rate (CSR) was calculated according to the life table method and illustrated with Kaplan-Meier survival curves. Univariate analysis was performed to investigate the association between study variables and time to implant failure. Variables with P -value < 0.15 were further selected for a multivariate analysis. Statistical methods which take into account the fact that some patients have more than one implant (therefore, dependency between implants within mouth) had been applied. RESULTS: At the implant level, the cumulative survival rates at 3, 5, and 7 years were 99.3%, 99.0%, and 98.4%, respectively, and at the patient level, they were 98.6%, 97.7%, and 95.9%, respectively. After adjustment to possible confounders, the multivariate analysis identified a relationship between the following risk indicators for implant failure: implant location, length and design, timing of implantation, bone grafting procedures and gender. Tissue-Level implants (n = 3863) had a very high survival rate of 99% at 3 years, which was maintained over the entire study period. Bone-Level implants (n = 600) were as predictable with a survival rate of 99% up to 3 years, while Tapered Effect implants (n = 128) demonstrated a lower survival rate of 95% at 5 years. Short 6 mm implants in the mandibular posterior sites had a high survival rate of 100%, while in maxillary posterior positions a survival rate of only 87% was achieved. Patient factors such as smoking, autoimmune disease, and penicillin allergy were tending to associate with higher failure rates. CONCLUSION: High long-term survival rates were observed for a large cohort of Straumann implants. Tissue- and Bone-Level implants had higher survival rates than Tapered Effect implants, and although short implants faired well in the mandibular posterior sites, they faired less well in the maxillary posterior sites. The study represents private practice insight into large-scale, long-term implant results. PMID- 25134416 TI - Quantification of nitrate sources to an urban stream using dual nitrate isotopes. AB - Human-engineered landscapes and subsequent altered hydrology affect the fate and transport of reactive nitrogen, particularly in urban watersheds. In this study, we used dual-nitrate isotopes and mixing model analysis (delta(15)N and delta(18)O of NO3(-)) to quantify nitrogen inputs from two sources concentrated in urban systems, sewage and atmospheric deposition. Analysis was conducted on samples collected from Nine Mile Run (Pittsburgh, PA) including over two years of samples collected biweekly and samples collected through the hydrographs of four storm events. Mixing models incorporated uncertainties in the isotopic composition of potential nitrate sources and resolved the relative proportions of nitrate inputs from each source using Bayesian techniques. The results indicate that up to 94% of nitrate in streamwater originated from sewage sources during baseflow conditions. During storms, atmospheric deposition was a substantial nitrate source (~ 34%) to total event-based nitrate loads, although sewage derived nitrate remained the dominant source (66%). The potential influence of denitrification was considered by incorporating associated isotopic fractionations into mixing models; up to 19% of sewage-derived samples showed the isotopic effects of denitrification. This study quantitatively delineates proportions of nitrate from different sources to urban streamwater, while incorporating remaining uncertainties in source endmember compositions. PMID- 25134418 TI - High pressure study of Li-doped fullerides, Li(x)C60 (x = 4,12), by x-ray diffraction and Raman spectroscopy. AB - In this article we study the alkali metal-intercalated 2D polymeric Li4C60 and the monomeric Li12C60 under pressure up to 40 GPa at room temperature, using x ray diffraction and Raman spectroscopy. Li4C60 undergoes several transitions in the studied pressure range. At pressures lower than 8 GPa, we observed changes in both diffraction patterns and Raman scattering spectra, probably due to the displacement of Li atoms. At 8 GPa another structural and electronic transition occurs. We observe an enhancement of background and a broadening of diffraction peaks. Raman modes weaken and broaden considerably. An important structural transition occurs at around 16 GPa, in which new Raman bands exhibit features similar to those of a reported 3D C60 polymeric structure. The XRD data shows a collapse in volume with the simultaneous formation of amorphous material. The cell parameters deviate from their early pressure evolution and become less compressible. The high pressure study of highly doped monomeric Li12C60 shows that its structural integrity is retained up to 13 GPa, with increasing pressure induced structural distortion and disorder. Above 13 GPa, Li12C60 transforms to a highly disordered state. PMID- 25134417 TI - Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo. AB - BACKGROUND: Yanhusuo (Corydalis yanhusuo W.T. Wang; YHS), is a well-known traditional Chinese herbal medicine, has been used in China for treating pain including chest pain, epigastric pain, and dysmenorrhea. Its alkaloid ingredients including tetrahydropalmatine are reported to inhibit cytochromes P450 (CYPs) activity in vitro. The present study is aimed to assess the potential of total alkaloid extract (TAE) from YHS to effect the activity and mRNA levels of five cytochromes P450 (CYPs) in rat. METHODS: Rats were administered TAE from YHS (0, 6, 30, and 150 mg/kg, daily) for 14 days, alanine aminotransferase (ALT) levels in serum were assayed, and hematoxylin and eosin-stained sections of the liver were prepared for light microscopy. The effects of TAE on five CYPs activity and mRNA levels were quantitated by cocktail probe drugs using a rapid chromatography/tandem mass spectrometry (LC-MS/MS) method and reverse transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS: In general, serum ALT levels showed no significant changes, and the histopathology appeared largely normal compared with that in the control rats. At 30 and 150 mg/kg TAE dosages, an increase in liver CYP2E1 and CYP3A1 enzyme activity were observed. Moreover, the mRNA levels of CYP2E1 and CYP3A1 in the rat liver, lung, and intestine were significantly up-regulated with TAE from 6 and 30 mg/kg, respectively. Furthermore, treatment with TAE (150 mg/kg) enhanced the activities and the mRNA levels of CYP1A2 and CYP2C11 in rats. However, the activity or mRNA level of CYP2D1 remained unchanged. CONCLUSIONS: These results suggest that TAE induced CYPs activity in the rat liver results from the elevated mRNA levels of CYPs. Co-administration of prescriptions containing YHS should consider a potential herb (drug)-drug interaction mediated by the induction of CYP2E1 and CYP3A1 enzymes. PMID- 25134419 TI - Survival of Escherichia coli O157:H7 during manufacture and storage of white brined cheese. AB - Escherichia coli O157:H7 is a major foodborne pathogen that causes severe disease in humans. Survival of E. coli O157:H7 during processing and storage of white brined cheese was investigated. Cheeses were prepared using pasteurized milk inoculated with a 4 strain E. coli O157:H7 cocktail (7 log(10) CFU/g) with or without yogurt starter culture (Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus salivarius ssp. thermophilus) and stored in 10% or 15% NaCl brine at 10 and 21 oC for 28 d. NaCl concentration, water activity (a(w)), pH, and numbers of E. coli O157:H7 and lactic acid bacteria (LAB) were determined in cheese and brine. E. coli O157:H7 was able to survive in cheese stored in both brines at 10 and 21 oC regardless of the presence of starter LAB, although the latter significantly enhanced E. coli O157:H7 reduction in cheese or its brine at 10 oC. E. coli O157:H7 numbers were reduced by 2.6 and 3.4 log(10) CFU/g in cheese stored in 10% and 15% NaCl brine, respectively, in the presence of starter LAB and by 1.4 and 2.3 log(10) CFU/g, respectively, in the absence of starter LAB at 10 oC. The pathogen survived, but at lower numbers in the brines. The salt concentration of cheese stored in 10% brine remained about 5% during ripening, but in 15% brine, the NaCl level increased 1.6% to 8.1% (w/w) by 28 d. Values of pH and a(w) slightly decreased 1 d after exposure to brine and reached 5.5 to 6.6 and 0.88 to 0.94, respectively, in all treatments. PMID- 25134420 TI - What is your diagnosis? Perianal gland mass in a cat. Anal sac gland carcinoma. PMID- 25134421 TI - Characteristics associated with drug-induced liver injury from interferon beta in multiple sclerosis patients. AB - OBJECTIVE: To identify and characterize drug-induced liver injury (DILI) associated with IFN-beta in multiple sclerosis (MS) using recommended criteria. METHODS: This retrospective, mixed methods design included a cohort of IFN-beta exposed MS patients from British Columbia (BC), Canada and a series of DILI cases from other Canadian provinces and two adverse drug reaction (ADR) networks (USA and Sweden). Associations between sex, age and IFN-beta product, and DILI were explored in BC cohort using Cox proportional hazard analyses. Characteristics, including the time to DILI, were compared between sites. RESULTS: In BC, 18/942 (1.9%) of IFN-beta exposed MS patients met criteria for DILI, with a trend toward an increased risk for women and those exposed to IFN-beta-1a SC (44 mcg 3 * weekly) (adjusted Hazard Ratios: 3.15;95% CI:0.72 - 13.72, p = 0.13 and 6.26;95%CI:0.78 - 50.39, p = 0.08, respectively). Twenty-four additional cases were identified from other sites; the median time to DILI was comparable between BC and other Canadian cases (105 and 90 days, respectively), but longer for the ADR network cases (590 days, p = 0.006). CONCLUSIONS: Approximately 1 in 50 IFN beta exposed patients developed DILI in BC, Canada. Identification of DILI cases from diverse sources highlighted that this reaction occurs even after years of exposure. PMID- 25134422 TI - Compression therapy: scientific background and practical applications. AB - BACKGROUND: Compression bandaging is the most prevalent form of treatment for venous leg ulcers. Successful treatment requires knowledge of the appropriate materials and the ability to employ them following current guidelines. This study investigates German health-care providers for their knowledge of bandage materials and their practical ability in applying short-stretch compression bandages. PARTICIPANTS AND METHODS: Within the framework of nationwide practical education on compression therapy, the participants' knowledge was quantified by asking standardized questions. Furthermore, their practical ability was evaluated by having them apply compression bandages within a pressure range of 50-60 mmHg. Another criterion was the pressure drop after a four-time dorsiflexion. RESULTS: Overall, 891 providers (3.3 % physicians, 5.5 % medical assistants, 90.7 % nursing staff) participated. Within the practical test only few (just under 10%) applied the bandages with the intended pressure; 77.0 % applied them below and 13.7 % above the target pressure. After a four-time dorsiflexion there was an average pressure drop of 6.7 mmHg. Surveying the participant's skills revealed that only 11.9 % knew about padding beneath compression bandages, 15.0 % knew of multi-component systems, and 14.8 % were familiar with ulcer stocking systems. CONCLUSIONS: Clearly, compression material and its application are unfamiliar to most practice employees. Without question there are deficits in the provision of compression therapy. PMID- 25134424 TI - How does drag affect the underwater phase of a swimming start? AB - During the underwater phase of the swimming start drag forces are constantly acting to slow the swimmer down. The current study aimed to quantify total drag force as well as the specific contribution of wave drag during the underwater phase of the swimming start. Swimmers were towed at three different depths (surface, 0.5 m, 1.0 m) and four speeds (1.6, 1.9, 2.0, 2.5 m . s(-1)), totaling 12 conditions. Wave drag and total drag were measured for each trial. Mixed modeling and plots were then used to determine the relationships between each towing condition and the amount of drag acting on the swimmer. The results of this study show large decreases in total drag as depth increases, regardless of speed (-19.7% at 0.5 m and -23.8% at 1.0 m). This is largely due to the significant reduction in wave drag as the swimmers traveled at greater depth. It is recommended that swimmers travel at least 0.5 m below the surface to avoid excessive drag forces. Swimmers should also perform efficient breakouts when transitioning into free swimming to reduce the duration spent just below the surface where drag values are reported at their highest. PMID- 25134423 TI - Co-occurrence of transcription and translation gene regulatory features underlies coordinated mRNA and protein synthesis. AB - BACKGROUND: Variability in protein levels is generated through intricate control of the different gene decoding phases. Presently little is known about the links between the various gene expression stages. Here we investigated the relationship between transcription and translation regulatory properties encoded in mammalian genes. RESULTS: We found that the TATA-box, a core promoter element known to enhance transcriptional output, is associated not only with higher mRNA levels but also with positive translation regulatory features and elevated translation efficiency. Further investigation revealed general association between transcription and translation regulatory trends. Specifically, translation inhibitory features such as the presence of upstream AUG (uAUG) and increased lengths of the 5'UTR, the coding sequence and the 3'UTR, are strongly associated with lower translation as well as lower transcriptional rate. CONCLUSIONS: Our findings reveal that co-occurrence of several gene-encoded transcription and translation regulatory features with the same trend substantially contributes to the final mRNA and protein expression levels and enables their coordination. PMID- 25134425 TI - Common misconceptions about data analysis and statistics. PMID- 25134426 TI - Relationship between buckling of acupuncture needles and the handle type. AB - BACKGROUND: Most popular single-use acupuncture needles consist of a stainless steel shaft with a handle made of copper coil or plastic stick. OBJECTIVES: To determine the strengths and weaknesses of these two handle types for needle buckling. METHODS: The buckling load for acupuncture needles with these two different handle types was determined using a digital scale, and the stiffness of stainless steel wires used in different types of acupuncture needles was measured using a Dynamic Mechanical Analysis machine. RESULTS: This study showed that an acupuncture needle with a copper coil handle was far more susceptible to buckling than a needle with a plastic stick handle. The average buckling force of acupuncture needles with plastic stick handles was 46.7% higher than that with copper coil handles for needles of 0.25 mm*30 mm, and 30.8% higher for needles of 0.25 mm*60 mm. Replacing a copper coil handle with a plastic stick handle could save about 100 tonnes of copper wires and 20 million metres of medical grade stainless steel wire a year worldwide. CONCLUSIONS: The results from this study suggest that the common practice of using coiled copper for handles on acupuncture needles should be re-evaluated. Replacing a copper coil handle with a plastic stick handle would significantly reduce needle buckling and improve patient comfort and safety. This would also reduce the consumption of copper and medical grade stainless steel wire considerably. PMID- 25134427 TI - Development of an evidence-based exercise programme for people with hand osteoarthritis. AB - BACKGROUND: Exercising is recommended for people with hand osteoarthritis (HOA), but there is no consensus regarding the design of exercise programmes. OBJECTIVE: To describe the development and content of an evidence-based exercise programme for people with HOA. METHODS: The development was based on research evidence, professional expertise, and client evidence and adhered to the new Medical Research Council framework for design and evaluation of complex interventions. The process included literature search and appraisal, discussions with clinicians and patient research partners, and piloting, followed by a revision of the programme based on feedback from pilot participants. RESULTS: The programme contains three exercises to increase the strength and stability of the shoulder, arm and wrist muscles, and four exercises to maintain or increase range of motion, grip strength, and joint stability in the finger joints. It starts with a warm-up period, ends with a finger stretch exercise, and follows the American College of Sports Medicine's recommendations regarding exercise intensity, session frequency, and length of exercise period. An exercise diary is included as part of the programme. CONCLUSIONS: An evidence-based exercise programme for people with HOA has been developed. The effect of the programme has recently been evaluated in a randomized controlled trial. PMID- 25134428 TI - Structure-activity relationships of N-benzylsalicylamides for inhibition of photosynthetic electron transport. AB - Inhibition of photosynthetic electron transport (PET) in spinach chloroplasts by sixty-one ring-substituted N-benzylsalicylamides was investigated. The inhibitory potency of the compounds expressed by IC50 value varied from 2.0 to 425.3 MUmol/L. Several evaluated compounds can be considered as effective PET inhibitors; these include N-(3,4- dichlorobenzyl)-2-hydroxy-5-nitrobenzamide (IC50 = 2.0 MUmol/L), 3,5-dibromo-N-(3,4-dichlorobenzyl)-2-hydroxybenzamide (IC50 = 2.3 MUmol/L) and 3,5-dibromo-N-(4-chlorobenzyl)-2-hydroxybenzamide (IC50 = 2.6 MUmol/L) with activity comparable with that of the standard Diuron (IC50 = 1.9 MUmol/L). The PET inhibiting activity increased approximately linearly with increasing lipophilicity of the compounds as well as with the increasing sum of Hammett sigma constants of the substituents on the acyl fragment (R(1) = H, 5 OCH3, 5-CH3, 5-Cl, 5-Br, 5-NO2, 4-OCH3, 4-Cl, 3,5-Cl and 3,5-Br) and the benzylamide fragment (R(2) = H, 4-OCH3, 4-CH3, 4-F, 4-Cl and 3,4-Cl). Based on the evaluated structure-PET inhibiting activity relationships (QSAR) it was confirmed that the inhibitory activity of the compounds depends on lipophilicity (log P or distributive parameters pi; (1) and pi(2)of individual substituents) and electronic properties of the substituents on the acyl (sigma(1)) and the benzylamide fragments (sigma(2)), the contribution of sigma(1) being more significant than that of sigma(2). PMID- 25134429 TI - Design, synthesis, and antitumor activity of novel acylate of 6-OH at 1- O acetylbritannilactone. AB - N-(alpha-Alkyloxime-3-phenylpropionyl) proline was designed and synthesized as an acylating agent to modify the 6-OH of 1-O-acetylbritannilactone. Eight intermediates and eight target compounds were obtained. The structures of sixteen novel compounds were characterized by (1)HNMR, IR and HRMS. The activities against HL-60 and Bel-7402 cell lines were tested, the IC50 values of compound IVg were 2.7 MUM and 4.3 MUM, respectively. PMID- 25134430 TI - Synthesis and evaluation of benzimidazole derivatives as selective COX-2 inhibitors. AB - A new series of 1-{(5-substituted-alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl}-2 (piperidin-1-ylmethyl)-1Hbenzimidazoles (5a-5r) was synthesized and screened for their inhibitory activity against COX (1 and 2). In vivo antiinflammatory activity of potent compounds was done by carrageenan-induced rat paw edema model. In vitro anticancer activity of synthesized compounds was also performed at the National Cancer Institute (NCI) against NCI 60 cell lines panel. Out of the 18 compounds screened, 5h, 5i, 5j and 5l were found to be potent COX-2 inhibitors in the range of IC50 0.06-0.81 MUM. In vivo anti-inflammatory screening results revealed that the compounds 5h and 5j manifested profound percent protection of 72.8 and 75.0%, respectively. Compound 5f exhibited moderate cytotoxicity with 58.79% growth inhibition against SNB-75 (CNS Cancer) cell lines and moderate activity against COX-2 (IC50 = 8.0 MUM). PMID- 25134431 TI - Continuing professional development training needs of medical laboratory personnel in Botswana. AB - BACKGROUND: Laboratory professionals are expected to maintain their knowledge on the most recent advances in laboratory testing and continuing professional development (CPD) programs can address this expectation. In developing countries, accessing CPD programs is a major challenge for laboratory personnel, partly due to their limited availability. An assessment was conducted among clinical laboratory workforce in Botswana to identify and prioritize CPD training needs as well as preferred modes of CPD delivery. METHODS: A self-administered questionnaire was disseminated to medical laboratory scientists and technicians registered with the Botswana Health Professions Council. Questions were organized into domains of competency related to (i) quality management systems, (ii) technical competence, (iii) laboratory management, leadership, and coaching, and (iv) pathophysiology, data interpretation, and research. Participants were asked to rank their self-perceived training needs using a 3-point scale in order of importance (most, moderate, and least). Furthermore, participants were asked to select any three preferences for delivery formats for the CPD. RESULTS: Out of 350 questionnaires that were distributed, 275 were completed and returned giving an overall response rate of 79%. The most frequently selected topics for training in rank order according to key themes were (mean, range) (i) quality management systems, most important (79%, 74-84%); (ii) pathophysiology, data interpretation, and research (68%, 52-78%); (iii) technical competence (65%, 44-73%); and (iv) laboratory management, leadership, and coaching (60%, 37-77%). The top three topics selected by the participants were (i) quality systems essentials for medical laboratory, (ii) implementing a quality management system, and (iii) techniques to identify and control sources of error in laboratory procedures. The top three preferred CPD delivery modes, in rank order, were training workshops, hands-on workshops, and internet-based learning. Journal clubs at the workplace was the least preferred method of delivery of CPD credits. CONCLUSIONS: CPD programs to be developed should focus on topics that address quality management systems, case studies, competence assessment, and customer care. The findings from this survey can also inform medical laboratory pre-service education curriculum. PMID- 25134432 TI - Re-development of mental health first aid guidelines for non-suicidal self injury: a Delphi study. AB - BACKGROUND: Up to 12% of Australian adults and almost one in five adolescents are estimated to have engaged in non-suicidal self-injury (NSSI) at some time in their life. Friends and family are most likely to notice signs of NSSI, but may be unsure how to intervene. Mental health first aid guidelines were developed in 2008 on how to do this through providing initial support and encouraging appropriate professional help-seeking. This study aims to re-develop the 2008 NSSI first aid guidelines to ensure they contain current recommended helping actions and remain consistent with the NSSI intervention literature. METHODS: The Delphi consensus method was used to determine the importance of the inclusion of helping statements in the guidelines. These statements describe helping actions a member of the public can take, and information they should have, to help someone who is engaging in NSSI. Systematic searches of the available NSSI intervention literature were conducted to find helping statements. Two expert panels, comprising 28 NSSI professionals and 33 consumer advocates, rated the importance of each statement. RESULTS: 98 out of 220 statements were endorsed as appropriate helping actions in providing assistance to someone engaging in NSSI. These statements were used to form the updated mental health first aid guidelines for NSSI. CONCLUSION: The re-development of the guidelines has resulted in more comprehensive guidance than the original version (98 versus 30 statements containing helping actions). This substantial increase in endorsed statements adds detail and depth to the guidelines, as well as covers additional ways of providing guidance and support. PMID- 25134435 TI - A physical model of sprinting. AB - A new physical model of all-out sprinting is presented. The first models for the applied forces in the block, drive and maintenance phases, as well as for braking forces, are proposed and are based on experimental observations. The applied forces and the aerodynamic drag forces along with the speed and position of the sprinter are calculated by the model as functions of time. The model's unknown parameters are physically relevant and are quantitatively comparable to quantities measured experimentally. A novel mathematical method, not based on curve fitting, is proposed along with the model which requires two observable quantities, time of first step and start of maintenance phase, and four time splits. The model was validated by modeling several elite sprints from available split data, as well as measured splits for non-elite sprinters, over 100 m and 200 m distances. Excellent agreement between the split times and the simulated times was obtained and the model was shown to accurately predict 100 m times from 60 m splits for non-elite runners and 200 m times from 100 m splits for elite sprinters. The model was also applied to the study of wind and altitude effects for elite sprinters in 100 and 200 m sprints. The model presented in this paper may also be useful as a coaching tool for non-elite sprinters by enabling comparisons with elite sprinters, the identification of weaknesses (comparing phases, braking coefficient) and by allowing predictions of 100 m times based on 60 m (indoor) performances and 200 m times based on 100 m splits. PMID- 25134433 TI - Variable NF-kappaB pathway responses in colon cancer cells treated with chemotherapeutic drugs. AB - BACKGROUND: The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathway is activated in cells exposed to various stimuli, including those originating on the cell surface or in the nucleus. Activated NF kappaB signaling is thought to enhance cell survival in response to these stimuli, which include chemotherapy and radiation. In the present effort, we determined which anticancer drugs preferentially activate NF-kappaB in colon cancer cells. METHODS: NF-kappaB reporter cells were established and treated with 5-fluorouracil (5-FU, DNA/RNA damaging), oxaliplatin (DNA damaging), camptothecin (CTP, topoisomerase inhibitor), phleomycin (radiomimetic), or erlotinib (EGFR inhibitor). The activation of NF-kappaB was assessed by immunofluorescence for p65 translocation, luciferase assays, and downstream targets of NF-kappaB activation (cIAP2, and Bcl-XL) were evaluated by immunoblotting, by ELISA (CXCL8 and IL-6 in culture supernatants), or by gene expression analysis. RESULTS: Colon cancer cells responded variably to different classes of therapeutic agents, and these agents initiated variable responses among different cell types. CPT activated NF-kappaB in SW480 colon cancer cells in a dose-dependent manner, but not in HCT116 cells that were either wild-type or deficient for p53. In SW480 colon cancer cells, NF-kappaB activation by CPT was accompanied by secretion of the cytokine CXCL8, but not by up-regulation of the anti-apoptotic genes, cIAP2 or Bcl-XL. On the contrary, treatment of HCT116 cells with CPT resulted in up regulation of CXCR2, a receptor for CXCL8, without an increase in cytokine levels. In SW480 cells, NF-kappaB reporter activity, but not cytokine secretion, was inhibited by SM-7368, an NF-kappaB inhibitor. CONCLUSION: The results show that, in response to cancer therapeutic agents, NF-kappaB activation varies with the cellular make up and that drug-induced NF-kappaB activation may be functionally uncoupled from anti-apoptotic outcomes found for other stimuli. Some cancer cells in a heterogeneous tumor tissue may, under therapeutic pressure, release soluble factors that have paracrine activity on neighboring cells that express the cognate receptors. PMID- 25134434 TI - Continuum description of the Poisson's ratio of ligament and tendon under finite deformation. AB - Ligaments and tendons undergo volume loss when stretched along the primary fiber axis, which is evident by the large, strain-dependent Poisson's ratios measured during quasi-static tensile tests. Continuum constitutive models that have been used to describe ligament material behavior generally assume incompressibility, which does not reflect the volumetric material behavior seen experimentally. We developed a strain energy equation that describes large, strain dependent Poisson's ratios and nonlinear, transversely isotropic behavior using a novel method to numerically enforce the desired volumetric behavior. The Cauchy stress and spatial elasticity tensors for this strain energy equation were derived and implemented in the FEBio finite element software (www.febio.org). As part of this objective, we derived the Cauchy stress and spatial elasticity tensors for a compressible transversely isotropic material, which to our knowledge have not appeared previously in the literature. Elastic simulations demonstrated that the model predicted the nonlinear, upwardly concave uniaxial stress-strain behavior while also predicting a strain-dependent Poisson's ratio. Biphasic simulations of stress relaxation predicted a large outward fluid flux and substantial relaxation of the peak stress. Thus, the results of this study demonstrate that the viscoelastic behavior of ligaments and tendons can be predicted by modeling fluid movement when combined with a large Poisson's ratio. Further, the constitutive framework provides the means for accurate simulations of ligament volumetric material behavior without the need to resort to micromechanical or homogenization methods, thus facilitating its use in large scale, whole joint models. PMID- 25134436 TI - Simple finite element models for use in the design of therapeutic footwear. AB - Therapeutic footwear is frequently prescribed in cases of rheumatoid arthritis and diabetes to relieve or redistribute high plantar pressures in the region of the metatarsal heads. Few guidelines exist as to how these interventions should be designed and what effect such interventions actually have on the plantar pressure distribution. Finite element analysis has the potential to assist in the design process by refining a given intervention or identifying an optimal intervention without having to actually build and test each condition. However, complete and detailed foot models based on medical image segmentation have proven time consuming to build and computationally expensive to solve, hindering their utility in practice. Therefore, the goal of the current work was to determine if a simplified patient-specific model could be used to assist in the design of foot orthoses to reduce the plantar pressure in the metatarsal head region. The approach is illustrated by a case study of a diabetic patient experiencing high pressures and pain over the fifth metatarsal head. The simple foot model was initially calibrated by adjusting the individual loads on the metatarsals to approximate measured peak plantar pressure distributions in the barefoot condition to within 3%. This loading was used in various shod conditions to identify an effective orthosis. Model results for metatarsal pads were considerably higher than measured values but predictions for uniform surfaces were generally within 16% of measured values. The approach enabled virtual prototyping of the orthoses, identifying the most favorable approach to redistribute the patient's plantar pressures. PMID- 25134438 TI - Transition-metal-catalyzed ring expansion of diazocarbonylated cyclic N hydroxylamines: a new approach to cyclic ketonitrones. AB - Novel C-ethoxycarbonyl cyclic ketonitrones are synthesized from the Ag- or Cu catalyzed ring expansion of beta-diazo cyclic hydroxylamines. The latter are themselves easily obtained by the addition of lithiated ethyl diazoacetate onto cyclic nitrones. The regioselective metal-catalyzed rearrangement of beta-diazo cyclic hydroxylamines proved highly efficient and resulted in a synthetically useful ring expansion to produce 6- or 7-membered ring functionalized nitrones. The outcome of the two steps, i.e. nucleophilic addition of alpha-diazoesters to nitrones and ring expansion, is a formal nitrone homologation. PMID- 25134437 TI - Cigarette smoke extract-induced BEAS-2B cell apoptosis and anti-oxidative Nrf-2 up-regulation are mediated by ROS-stimulated p38 activation. AB - Cigarette smoke contains reactive oxygen (ROS) that can cause oxidative stress. It increases the number of apoptotic and necrotic lung cells and further induces the development of chronic airway disease. In this study, we investigated the effects of cigarette smoke extract (CSE) on apoptosis in human bronchial epithelial cells (BEAS-2B). CSE exposure induced ROS generation and p38 mitogen activated protein kinase (MAPK) activation that are associated with the activation of apoptosis-regulating signal kinase 1 (ASK-1). N-acetylcysteine (a general antioxidant) attenuated the CSE-induced ASK-1 and p38 MAPK activation and cell apoptosis, suggesting a triggering role of ROS in ASK-1/p38 MAPK activation during apoptotic progression. In contrast, the inhibition and knockdown of p38 attenuated the expression of anti-oxidant master NF-E2-related factor 2 (Nrf-2) and CSE-induced apoptosis, suggesting that p38 MAPK modulates Nrf-2 expression and presumably prevents cell apoptosis. Taken together, the data presented in this manuscript demonstrate that the ROS-dependent ASK-1/p38 signaling cascade regulates CSE-induced BEAS-2B cell apoptosis. In addition, anti-oxidative Nrf-2 is also up-regulated by the ROS/p38 signaling cascade in this progression. PMID- 25134439 TI - Pathogen reduction by ultraviolet C light effectively inactivates human white blood cells in platelet products. AB - BACKGROUND: Residual white blood cells (WBCs) in cellular blood components induce a variety of adverse immune events, including nonhemolytic febrile transfusion reactions, alloimmunization to HLA antigens, and transfusion-associated graft versus-host disease (TA-GVHD). Pathogen reduction (PR) methods such as the ultraviolet C (UVC) light-based THERAFLEX UV-Platelets system were developed to reduce the risk of transfusion-transmitted infection. As UVC light targets nucleic acids, it interferes with the replication of both pathogens and WBCs. This preclinical study aimed to evaluate the ability of UVC light to inactivate contaminating WBCs in platelet concentrates (PCs). STUDY DESIGN AND METHODS: The in vitro and in vivo function of WBCs from UVC-treated PCs was compared to that of WBCs from gamma-irradiated and untreated PCs by measuring cell viability, proliferation, cytokine secretion, antigen presentation in vitro, and xenogeneic GVHD responses in a humanized mouse model. RESULTS: UVC light was at least as effective as gamma irradiation in preventing GVHD in the mouse model. It was more effective in suppressing T-cell proliferation (>5-log reduction in the limiting dilution assay), cytokine secretion, and antigen presentation than gamma irradiation. CONCLUSIONS: The THERAFLEX UV-Platelets (MacoPharma) PR system can substitute gamma irradiation for TA-GVHD prophylaxis in platelet (PLT) transfusion. Moreover, UVC treatment achieves suppression of antigen presentation and inhibition of cytokine accumulation during storage of PCs, which has potential benefits for transfusion recipients. PMID- 25134441 TI - Effects of sample injection amount and time-of-flight mass spectrometric detection dynamic range on metabolome analysis by high-performance chemical isotope labeling LC-MS. AB - The effect of sample injection amount on metabolome analysis in a chemical isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) platform was investigated. The performance of time-of-flight (TOF) mass spectrometers with and without a high-dynamic-range (HD) detection system was compared in the analysis of (12)C2/(13)C2-dansyl labeled human urine samples. An average of 1635 +/- 21 (n = 3) peak pairs or putative metabolites was detected using the HD-TOF MS, compared to 1429 +/- 37 peak pairs from a conventional or non-HD TOF-MS. In both instruments, signal saturation was observed. However, in the HD-TOF-MS, signal saturation was mainly caused by the ionization process, while in the non HD TOF-MS, it was caused by the detection process. To extend the MS detection range in the non-HD TOF-MS, an automated switching from using (12)C to (13)C natural abundance peaks for peak ratio calculation when the (12)C peaks are saturated has been implemented in IsoMS, a software tool for processing CIL LC-MS data. This work illustrates that injecting an optimal sample amount is important to maximize the metabolome coverage while avoiding the sample carryover problem often associated with over-injection. A TOF mass spectrometer with an enhanced detection dynamic range can also significantly increase the number of peak pairs detected. BIOLOGICAL SIGNIFICANCE: In chemical isotope labeling (CIL) LC-MS, relative metabolite quantification is done by measuring the peak ratio of a (13)C2-/(12)C2-labeled peak pair for a given metabolite present in two comparative samples. The dynamic range of peak ratio measurement does not need to be very large, as only subtle changes of metabolite concentrations are encountered in most metabolomic studies where relative metabolome quantification of different groups of samples is performed. However, the absolute concentrations of different metabolites can be very different, requiring a technique to provide a wide detection dynamic range to allow the detection of as many peak pairs as possible. In this work, we demonstrated that controlling the sample injection amount into LC-MS was critical to achieve the optimal detectability while avoiding sample carry-over problem. In addition, the use of a high-dynamic-range TOF system increased the number of peak pairs detected, compared to a conventional TOF system. We also investigated the ionization and detection saturation factors limiting the dynamic range of detection. This article is part of a Special Issue entitled: Protein dynamics in health and disease. Guest Editors: Pierre Thibault and Anne-Claude Gingras. PMID- 25134443 TI - Preventing primary cesareans: implications for laboring women, their partners, nurses, educators, and doulas. PMID- 25134442 TI - Can we safely reduce primary cesareans with greater patience? PMID- 25134445 TI - Family-centered neonatal intensive care. PMID- 25134440 TI - Acute kidney injury in major gynaecological surgery: an observational study. AB - OBJECTIVE: To assess the prevalence, outcomes and cost associated with acute kidney injury (AKI) defined by consensus risk, injury, failure, loss, and end stage kidney (RIFLE) criteria after gynaecologic surgery. DESIGN: Retrospective single-centre cohort study. SETTING: Academic medical centre. SAMPLE: Two thousand three hundred and forty-one adult women undergoing major inpatient gynaecologic surgery between January 2000 and November 2010. METHODS: AKI was defined by RIFLE criteria as an increase in serum creatinine greater than or equal to 50% from the reference creatinine. We used multivariable regression analyses to determine the association between perioperative factors, AKI, mortality and cost. MAIN OUTCOME MEASURES: AKI, combined major adverse events (hospital mortality, sepsis or mechanical ventilation), 90-day mortality and hospital cost. RESULTS: Overall prevalence of AKI was 13%. The prevalence of AKI was associated with the primary diagnosis. Of women with benign tumour surgeries, 5% (43/801) experienced AKI compared with 18% (211/1159) of women with malignant disease (P < 0.001). Only 1.3% of the whole cohort had evidence of urologic mechanical injury. In a multivariable logistic regression analysis, AKI patients had nine times the odds of a major adverse event compared to patients without AKI (adjusted odds ratio 8.95, 95% confidence interval 5.27-15.22). We have identified several readily available perioperative factors that can be used to identify patients at high risk for AKI after in-hospital gynaecologic surgery. CONCLUSIONS: AKI is a common complication after major inpatient gynaecologic surgery associated with an increase in resource utilisation and hospital cost, morbidity and mortality. PMID- 25134447 TI - The role of carbonic anhydrase VI in bitter taste perception: evidence from the Car6-/- mouse model. AB - BACKGROUND: Carbonic anhydrase VI (CA VI) is a secretory isozyme of the alpha-CA gene family. It is highly expressed in the salivary and mammary glands and secreted into saliva and milk. Although CA VI was first described as a gustatory protein, its exact functional roles have remained enigmatic. Interestingly, polymorphism of the CA6 gene was recently linked to bitter taste perception in humans. In this study, we compared the preference of Car6-/- and wild-type mice for different taste modalities in an IntelliCage monitoring environment. Morphologies of taste buds, tongue papillae, and von Ebner's glands were evaluated by light microscopy. Cell proliferation and rate of apoptosis in tongue specimens were examined by Ki67 immunostaining and fluorescent DNA fragmentation staining, respectively. RESULTS: The behavioral follow up of the mice in an IntelliCage system revealed that Car6-/- mice preferred 3 MUM quinine (bitter) solution, whereas wild type mice preferred water. When the quinine concentration increased, both groups preferentially selected water. Histological analysis, Ki67 immunostaining and detection of apoptosis did not reveal any significant changes between tongue specimens of the knockout and wild type mice. CONCLUSIONS: Our knockout mouse model confirms that CA VI is involved in bitter taste perception. CA VI may be one of the factors which contribute to avoidance of bitter, potentially harmful, substances. PMID- 25134448 TI - Rapamycin protects kidney against ischemia reperfusion injury through recruitment of NKT cells. AB - BACKGROUND: NKT cells play a protective role in ischemia reperfusion (IR) injury, of which the trafficking in the body and recruitment in injured organs can be influenced by immunosuppressive therapy. Therefore, we investigated the effects of rapamycin on kidneys exposed to IR injury in early stage and on trafficking of NKT cells in a murine model. MATERIAL AND METHODS: Balb/c mice were subjected to kidney 30 min ischemia followed by 24 h reperfusion. Rapamycin (2.5 ml/kg) was administered by gavage daily, starting 1 day before the operation. Renal function and histological changes were assessed. The proportion of NKT cells in peripheral blood, spleen and kidney was detected by flow cytometry. The chemokines and corresponding receptor involved in NKT cell trafficking were determined by RT-PCR and flow cytometry respectively. RESULTS: Rapamycin significantly improved renal function and ameliorated histological injury. In rapamycin-treated group, the proportion of NKT cells in spleen was significantly decreased but increased in peripheral blood and kidney. In addition, the CXCR3+ NKT cell in the kidney increased remarkably in the rapamycin-treated group. The chemokines, CXCL9 and CXCL10, as the ligands of CXCR3, were also increased in the rapamycin-treated kidney. CONCLUSIONS: Rapamycin may recruit NKT cells from spleen to the IR induced kidney to ameliorate renal IR injury in the early stage. PMID- 25134450 TI - The CROWN Initiative: Journal editors invite researchers to develop core outcomes in women's health. PMID- 25134449 TI - The PP4R1 subunit of protein phosphatase PP4 targets TRAF2 and TRAF6 to mediate inhibition of NF-kappaB activation. AB - TRAFs constitute a family of proteins that have been implicated in signal transduction by immunomodulatory cellular receptors and viral proteins. TRAF2 and TRAF6 have an E3-ubiquitin ligase activity, which is dependent on the integrity of their RING finger domain and it has been associated with their ability to activate the NF-kappaB and AP1 signaling pathways. A yeast two-hybrid screen with TRAF2 as bait, identified the regulatory subunit PP4R1 of protein phosphatase PP4 as a TRAF2-interacting protein. The interaction of TRAF2 with PP4R1 depended on the integrity of the RING finger domain of TRAF2. PP4R1 could interact also with the TRAF2-related factor TRAF6 in a RING domain-dependent manner. Exogenous expression of PP4R1 inhibited NF-kappaB activation by TRAF2, TRAF6, TNF and the Epstein-Barr virus oncoprotein LMP1. In addition, expression of PP4R1 downregulated IL8 induction by LMP1, whereas downregulation of PP4R1 by RNA interference enhanced the induction of IL8 by LMP1 and TNF. PP4R1 could mediate the dephosphorylation of TRAF2 Ser11, which has been previously implicated in TRAF2-mediated activation of NF-kappaB. Finally, PP4R1 could inhibit TRAF6 polyubiquitination, suggesting an interference with the E3 ubiquitin ligase activity of TRAF6. Taken together, our data identify a novel mechanism of NF kappaB pathway inhibition which is mediated by PP4R1-dependent targeting of specific TRAF molecules. PMID- 25134452 TI - Psychological distress among parents having offspring with autism spectrum disorder: Authors' reply. PMID- 25134451 TI - Paediatric vulvar disease. AB - Paediatric vulvar skin conditions are relatively common but often cause diagnostic difficulties for clinicians, which can lead to anxiety within the children's families. Vulvar skin conditions can be caused by various underlying aetiologies. Most are general dermatologic conditions that occur in the vulvar area, such as eczema, psoriasis, skin lesions or infections. However, other conditions such as lichen sclerosus and napkin dermatitis ('nappy rash') only affect the genital region. Every affected child needs a sensitive evaluation of the complaint including an assessment of the impact of the condition on the patient and her family. Paediatric vulvar disease often influences bowel and bladder habits and may lead to behavioural problems. General measures such as avoidance of irritants or soap substitution and regular use of emollients are helpful for all patients. Specific therapy depends upon the underlying diagnosis. Time spent reassuring the families, reinforcing regimens and providing written documentation can all be very helpful in successful management of paediatric vulvar skin conditions. PMID- 25134453 TI - The burden of false-positive results in analog and digital screening mammography: experience of the Nova Scotia Breast Screening Program. AB - PURPOSE: The Canadian Task Force on Preventive Health Care released recommendations for breast cancer screening, in part, based on harms associated with screening. The purpose of this study was to describe the rate of false positive (FP) screening mammograms and to describe the extent of the investigations after an FP. METHODS: A cohort was identified that consisted of all screening mammograms performed through the Screening Program (2000-2011) with patients ages 40-69 years at screening. Rates of FP screening mammograms were calculated as well as rates of further investigations required, including additional imaging, needle core biopsy, and surgery. Analyses were stratified by 10-year age group, screening status (first vs rescreen), and technology. RESULTS: A total of 608,088 screening mammograms were included. The FP rate varied by age group, and decreased with increasing age (digital, 40-49 years old, FP = 8.0%; 50 59 years old, FP = 6.3%; 60-69 years old, FP = 4.6%). The FP rate also varied by screening status (digital, first screen, FP = 12.0%; rescreen, FP = 5.6%), and this difference was consistent across age groups. The need for further investigation varied by age group, with invasive procedures being more heavily used as women age (digital, rescreen group, surgery: 40-49 years old, 1.1%; 50-59 years old 1.6%, 60-69 years old, 1.8%). CONCLUSIONS: Both the FP screening mammogram rate and the degree to which further investigation was required varied by age group and screening status. Reporting on these rates should form part of the evaluation of screening performance. PMID- 25134455 TI - Is Available Support Always Helpful for Older Adults? Exploring the Buffering Effects of State and Trait Social Support. AB - OBJECTIVES: Associations between social support and health are studied since decades. Yet, little is known about how they vary by state versus trait aspects of support and by adult age. At trait and state level, the current study investigates direct associations between social support and health and whether support buffers the daily negative affect (NA)-health association in 2 age groups. METHOD: Seventy-nine younger and 88 older adults (OA) participated in 20 daily assessments of NA, health complaints (HC), and available support. On trait and state levels, 3 support facets-emotional, informational, and instrumental were distinguished; social integration was assessed on the trait level. RESULTS: For OA, trait emotional support was associated with fewer HC. In both age groups, state informational support was related to more daily HC. Social integration buffered the daily NA-health association in younger adults (YA), whereas informational support amplified the same association in OA. DISCUSSION: We propose that 2 different mechanisms are relevant for younger and OA and at state and trait level. Although emotional support may be a resource for OA, informational support may enhance their daily complaints. YA seem to benefit from being socially integrated. PMID- 25134454 TI - Carotenoids, inflammation, and oxidative stress--implications of cellular signaling pathways and relation to chronic disease prevention. AB - Several epidemiologic studies have shown that diets rich in fruits and vegetables reduce the risk of developing several chronic diseases, such as type 2 diabetes, atherosclerosis, and cancer. These diseases are linked with systemic, low-grade chronic inflammation. Although controversy persists on the bioactive ingredients, several secondary plant metabolites have been associated with these beneficial health effects. Carotenoids represent the most abundant lipid-soluble phytochemicals, and in vitro and in vivo studies have suggested that they have antioxidant, antiapoptotic, and anti-inflammatory properties. Recently, many of these properties have been linked to the effect of carotenoids on intracellular signaling cascades, thereby influencing gene expression and protein translation. By blocking the translocation of nuclear factor kappaB to the nucleus, carotenoids are able to interact with the nuclear factor kappaB pathway and thus inhibit the downstream production of inflammatory cytokines, such as interleukin 8 or prostaglandin E2. Carotenoids can also block oxidative stress by interacting with the nuclear factor erythroid 2-related factor 2 pathway, enhancing its translocation into the nucleus, and activating phase II enzymes and antioxidants, such as glutathione-S-transferases. In this review, which is organized into in vitro, animal, and human investigations, we summarized current knowledge on carotenoids and metabolites with respect to their ability to modulate inflammatory and oxidative stress pathways and discuss potential dose-health relations. Although many pathways involved in the bioactivity of carotenoids have been revealed, future research should be directed toward dose-response relations of carotenoids, their metabolites, and their effect on transcription factors and metabolism. PMID- 25134456 TI - Subdural and intracerebral hemorrhage caused by spontaneous bleeding in the middle meningeal artery after coil embolization of a cerebral aneurysm. AB - Nontraumatic acute subdural hemorrhage (SDH) with intracerebral hemorrhage (ICH) is rare and is usually caused by severe bleeding from aneurysms or arteriovenous fistulas. We encountered a very rare case of spontaneous bleeding from the middle meningeal artery (MMA), which caused hemorrhage in the temporal lobe and subdural space 2 weeks after coil embolization of an ipsilateral, unruptured internal cerebral artery aneurysm in the cavernous portion. At onset, the distribution of hematoma on a computed tomography scan led us to believe that the treated intracavernous aneurysm could bleed into the intradural space. Emergency craniotomy revealed that the dura of the middle fossa was intact except for the point at the foramen spinosum where the exposed MMA was bleeding. Retrospectively, angiography just before and after embolization of the aneurysm did not show any aberrations in the MMA. Although the MMA usually courses on the outer surface of the dura and is unlikely to rupture without an external force, physicians should be aware that the MMA may bleed spontaneously and cause SDH and ICH. PMID- 25134457 TI - In vitro synergistic efficacy of conjugated linoleic acid, oleic acid, safflower oil and taxol cytotoxicity on PC3 cells. AB - The aim of this study was to determine in vitro synergistic efficacy of conjugated linoleic acid (CLA), oleic acid (OLA), safflower oil and taxol (Tax) cytotoxicity on human prostate cancer (PC3) cell line. To determine synergistic efficacy of oil combinations, PC3 treated with different doses of compounds alone and combined with 10 MUg/mL Tax. The MTT results indicated that OLA-Tax combinations exhibited cytotoxicity against PC3 at doses of 30 nM+10 MUg-Tax, 15 nM+5 MUg-Tax and 7.5 nM+2.5 MUg-Tax. The treatment of OLA or Tax did not show significant inhibition on PC3, while OLA-Tax combinations showed effective cytotoxicity at treated doses. CLA-Tax combinations demonstrated the same effect on PC3 as combined form with 45.72% versus the alone form as 74.51% viability. Cytotoxic synergy between Tax, OLA and CLA shows enhanced cytotoxicity on PC3 which might be used in the therapy of prostate cancer. PMID- 25134458 TI - Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells. AB - Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector cells from bone marrow and peripheral blood samples at diagnosis and at various stages of treatment by co-culture with artificial antigen-presenting K562 clone 9.mbIL-21 cells. Amplified CD56+CD3- cells had spontaneous and anti-B cell activating factor receptor mAb-stimulated ADCC activity against allogeneic ALL cells, which could be further enhanced by IL-15. Importantly, matched CD56+ effector cells also killed autologous ALL cells grown out from leukemia samples of the same patient, through both spontaneous as well as antibody-dependent cellular cytotoxicity. Since autologous cell therapy will not be complicated by graft-versus-host disease, our results show that expanded CD56+ cells could be applied for treatment of pre-B ALL without transplantation, or for purging of bone marrow in the setting of autologous bone marrow transplants. PMID- 25134460 TI - [Conjunctival amyloidosis]. AB - BACKGROUND: This article reports a case of primary localized conjunctival lambda light-chain (AL) amyloidosis. METHODS: Case report. RESULTS: A 73-year-old woman presented with a 1-year history of a painless growth in the conjunctiva of the left eye. A yellow-salmon pink diffuse mass of tissue was identified in the inferomedial bulbar conjunctiva and inferior fornix. An incisional biopsy was performed. The histopathological and immunohistochemical examinations revealed interstitial and vascular amyloid deposits of lambda light chains. The diagnosis was amyloidosis of the conjunctiva. The systemic evaluation revealed normal findings and systemic amyloidosis was excluded. Nevertheless, due to an unexplained cardiac insufficiency and after consultation with the treating hematologist a treatment with three cycles of systemic chemotherapy with melphalan and prednisolone was initiated but 6 months later the conjunctival mass in the inferior fornix showed persistence and complete excision was performed. At 16, 24 and 44 months of follow-up no evidence of recurrence was seen on clinical examination. The magnetic resonance imaging (MRI) at 16 and 24 months of follow up showed no associated cranial or orbital infiltration. CONCLUSION: Conjunctival AL amyloidosis is a rare clinical entity. Because of the heterogeneity of amyloidosis in clinical presentation, pattern of amyloid-related organ toxicity, association with lymphoproliferative diseases and rate of disease progression, identification of amyloid deposits is essential and systemic involvement has to be excluded. PMID- 25134462 TI - [Adjuvant anti-VEGF therapy in Coats' disease]. AB - BACKGROUND: Coats' disease is a non-hereditary acquired, usually unilateral eye disorder that predominantly occurs in young males (1/100,000) with the onset of symptoms generally appearing in the first two decades of life. Coats' disease is characterized by telangiectatic changes, blood leaks from the defective vessels with retinal exudation followed in advanced stages by retinal detachment. CASE REPORT: A 14-year-old male patient presented in our department with gradual visual loss in the right eye. Based on the clinical and diagnostic findings Coats' disease was diagnosed. The exudative retinal detachment in the right eye was initially treated with intravitreal bevacizumab injection (B-IVOM) followed by cryocoagulation and combined with a second administration of B-IVOM 2 weeks later. On the grounds of a persistent exudative retinal detachment a new round of cryotherapy was conducted. We proceeded with laser coagulation of the residual Coats areas and with three cycles of B-IVOM therapy. The subretinal and intraretinal exudates regressed over several weeks so that the patient remained symptom-free 22 months after therapy. At the last examination the visual acuity was 0.8 in the right eye. CONCLUSION: The favorable development for our patient demonstrates that adjuvant therapy with intravitreal anti-VEGF injections in addition to laser and cryocoagulation in a case of advanced Coats' disease with exudative retinal tissue damage could lead to the stabilization of the retinal findings and to preservation of good visual acuity. PMID- 25134463 TI - Stress-mediated tuning of developmental robustness and plasticity in flies. AB - Organisms have to be sufficiently robust to environmental and genetic perturbations, yet plastic enough to cope with stressful scenarios to which they are not fully adapted. How this apparent conflict between robustness and plasticity is resolved at the cellular and whole organism levels is not clear. Here we review and discuss evidence in flies suggesting that the environment can modulate the balance between robustness and plasticity. The outcomes of this modulation can vary from mild sensitizations that are hardly noticeable, to overt qualitative changes in phenotype. The effects could be at both the cellular and whole organism levels and can include cellular de-/trans-differentiation ('Cellular reprogramming') and gross disfigurements such as homeotic transformations ('Tissue/whole organism reprogramming'). When the stress is mild enough, plastic changes in some processes may prevent drastic changes in more robust traits such as cell identity and tissue integrity. However, when the stress is sufficiently severe, this buffering may no longer be able to prevent such overt changes, and the resulting phenotypic variability could be subjected to selection and might assist survival at the population level. This article is part of a Special Issue entitled: Stress as a fundamental theme in cell plasticity. PMID- 25134461 TI - [Corneal collagen cross-linking with riboflavin and ultraviolet-A light in progressive keratoconus. Results after 10-year follow-up]. AB - PURPOSE: Riboflavin and ultraviolet-A induced cross-linking (CXL) is a promising therapeutic option to halt the progression of keratoconus. The aim of the study was to prove a long-term stabilizing effect of riboflavin and ultraviolet-A induced collagen CXL in young and otherwise healthy patients with progressive keratoconus and a corneal thickness of at least 400 MUm on average 10 years after treatment. METHODS: Corneal CXL was performed after removing epithelial tissue by instilling riboflavin 0.1% solution for 30 min before and during 30 min of ultraviolet-A irradiation (370 nm, 3 mW/cm(2)). This long-term retrospective study included 30 eyes of 20 patients with progressive keratoconus. Preoperative and postoperative examinations on average 10 years after treatment included best corrected visual acuity (BCVA), corneal topography (keratometry values KMAX, KMIN and KApex), corneal thickness (CT) and if available endothelial cell density. RESULTS: The mean preoperative age was 28 +/- 7 years (range 14-42 years), 4 patients were female (7 eyes) and 16 patients (23 eyes) were male. Preoperatively, the mean K-value on the apex of keratoconus was 62 +/- 13.2 dpt which showed a statistically significant reduction after 10 years to 55 +/- 8.1 dpt (p = 0.001). The mean KMAX (53 +/- 8.2 versus 49 +/- 6.6 dpt) and KMIN values (48 +/- 5.5 vs. 45 +/- 5.1 dpt) also showed a statistically significant decrease (p = 0.001). In comparison BCVA also showed a statistically significant preoperative and postoperative difference (p = 0.005). There was a significant improvement of BCVA by a mean of - 0.13 +/- 0.25 logMAR. The mean change in corneal thickness at the 10-year follow up was 46 MUm (p = 0.001). Bias possibly occurred because of a change of the measurement method from ultrasound pachymetry to optical pachymetry with Oculus Pentacam(r). Neither corneal endothelium nor deeper structures suffered any damage. Only two patients had continuous progression of keratoconus and needed a reapplication of CXL. CONCLUSION: The results of this study indicate that riboflavin and ultraviolet-A induced corneal CXL is a promising therapeutic option for progressing keratoconus to obtain long term stabilization. There was a sustained improvement of all K-values and BCVA 10 years after treatment and CXL is minimally invasive and easy to handle. Side effects, such as endothelial damage did not occur. PMID- 25134465 TI - A trapped-ion-based quantum byte with 10(-5) next-neighbour cross-talk. AB - The addressing of a particular qubit within a quantum register is a key pre requisite for scalable quantum computing. In general, executing a quantum gate with a single qubit, or a subset of qubits, affects the quantum states of all other qubits. This reduced fidelity of the whole-quantum register could prevent the application of quantum error correction protocols and thus preclude scalability. Here we demonstrate addressing of individual qubits within a quantum byte (eight qubits) and measure the error induced in all non-addressed qubits (cross-talk) associated with the application of single-qubit gates. The quantum byte is implemented using microwave-driven hyperfine qubits of (171)Yb(+) ions confined in a Paul trap augmented with a magnetic gradient field. The measured cross-talk is on the order of 10(-5) and therefore below the threshold commonly agreed sufficient to efficiently realize fault-tolerant quantum computing. Hence, our results demonstrate how this threshold can be overcome with respect to cross talk. PMID- 25134459 TI - Combined STAT3 and BCR-ABL1 inhibition induces synthetic lethality in therapy resistant chronic myeloid leukemia. AB - Mutations in the BCR-ABL1 kinase domain are an established mechanism of tyrosine kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive leukemia, but fail to explain many cases of clinical TKI failure. In contrast, it is largely unknown why some patients fail TKI therapy despite continued suppression of BCR-ABL1 kinase activity, a situation termed BCR-ABL1 kinase-independent TKI resistance. Here, we identified activation of signal transducer and activator of transcription 3 (STAT3) by extrinsic or intrinsic mechanisms as an essential feature of BCR-ABL1 kinase-independent TKI resistance. By combining synthetic chemistry, in vitro reporter assays, and molecular dynamics-guided rational inhibitor design and high-throughput screening, we discovered BP-5-087, a potent and selective STAT3 SH2 domain inhibitor that reduces STAT3 phosphorylation and nuclear transactivation. Computational simulations, fluorescence polarization assays and hydrogen-deuterium exchange assays establish direct engagement of STAT3 by BP-5-087 and provide a high-resolution view of the STAT3 SH2 domain/BP-5 087 interface. In primary cells from chronic myeloid leukemia (CML) patients with BCR-ABL1 kinase-independent TKI resistance, BP-5-087 (1.0 MUM) restored TKI sensitivity to therapy-resistant CML progenitor cells, including leukemic stem cells. Our findings implicate STAT3 as a critical signaling node in BCR-ABL1 kinase-independent TKI resistance, and suggest that BP-5-087 has clinical utility for treating malignancies characterized by STAT3 activation. PMID- 25134464 TI - beta-Arrestins regulate human cardiac fibroblast transformation and collagen synthesis in adverse ventricular remodeling. AB - Cardiac fibroblasts (CFs) produce and degrade the myocardial extracellular matrix and are critical in maladaptive ventricular remodeling that can result in heart failure (HF). beta-Arrestins are important signaling molecules involved in beta adrenergic receptor (beta-AR) desensitization and can also mediate signaling in a G protein-independent fashion. We hypothesize that beta-arrestins play an important role in the regulation of adult human CF biology with regard to myofibroblast transformation, increased collagen synthesis, and myocardial fibrosis which are important in the development of HF. beta-Arrestin1 & 2 expression is significantly upregulated in adult human CF isolated from failing left ventricles and beta-AR signaling is uncoupled with loss of beta-agonist mediated inhibition of collagen synthesis versus normal control CF. Knockdown of either beta-arrestin1 or 2 restored beta-AR signaling and beta-agonist mediated inhibition of collagen synthesis. Overexpression of beta-arrestins in normal CF led to a failing phenotype with increased baseline collagen synthesis, impaired beta-AR signaling, and loss of beta-agonist-mediated inhibition of collagen synthesis. beta-Arrestin knockdown in failing CF diminished TGF-beta stimulated collagen synthesis and also inhibited ERK phosphorylation. Overexpression of beta arrestins in normal CF increased basal ERK1/2 and Smad2/3 phosphorylation and enhanced TGF-beta-stimulated collagen synthesis. This was prevented by pre treatment with a MEK1/2 inhibitor. Enhanced beta-arrestin signaling appears to be deleterious in CF by promoting a pro-fibrotic phenotype via uncoupling of beta-AR signaling as well as potentiating ERK and Smad signaling. Targeted inhibition of beta-arrestins in CF may represent a therapeutic strategy to prevent maladaptive myocardial fibrosis. PMID- 25134467 TI - Effect of backing films on the transdermal delivery of donepezil from patches. AB - The aim of this work was to investigate the effect of backing films on transdermal delivery of donepezil (DP) from patches. Three backing films, CotranTM 9700, CotranTM 9701, and CotranTM 9726 were chosen as backing layers to prepare transdermal patches containing DP. The transdermal penetration and release amount of DP from each patch were evaluated by rabbit abdominal skin in vitro. The partitioning experiments and attentuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were performed to confirm the existence of interaction between backing films and DP. Results showed that the cumulative release amount of DP from patches with different backing films had the same order of cumulative amount penetrated, i.e. CotranTM 9701 < CotranTM 9700 < CotranTM 9726, which demonstrated that the permeation of DP was mainly limited by release behavior. Partitioning experiments and ATR-FTIR study indicated that CotranTM 9700 and CotranTM 9701 had interaction with DP by H bond formation which decreased the release of drug from the patches. By contrast, CotranTM 9726 could provide the highest flux of skin permeation of DP, because such interaction between them was not found. Moreover, the parameters of backing films were found to have relation to skin hydration, thus affecting the penetration behavior of DP from patches. In conclusion, the effect of backing films on the flux of DP permeation could be attributed to both the interaction of backing films and the changes of skin hydration. Backing films could be a key factor in formulation screening of DP patches. PMID- 25134468 TI - Human stem cell-derived cardiomyocytes in cellular impedance assays: bringing cardiotoxicity screening to the front line. AB - Cardiovascular (CV) toxicity is a leading cause of drug attrition and withdrawal. Introducing in vitro assays with higher throughput should permit earlier CV hazard identification and enable medicinal chemists to design-out liabilities. Heretofore, development of in vitro CV assays has been limited by the challenge of replicating integrated cardiovascular physiology while achieving the throughput and consistency required for screening. These challenges appear to be met with a combination of human stem cell-derived cardiomyocytes (CM) which beat spontaneously and monitoring the response with technology that can assess drug induced changes in voltage dependent contraction such as cellular impedance which has been validated with excellent predictivity for drug-induced arrhythmia and contractility. Here, we review advances in cardiomyocyte impedance with emphasis on stem cell-derived cardiomyocyte models for toxicity screening. Key perspectives include: the electrical principles of impedance technology, impedance detection of cardiomyocyte beating, beat parameter selection/analysis, validation in toxicity and drug discovery, and future directions. As a conclusion, an in vitro screening cascade is proffered using the downstream, inclusive detection of CM impedance assays as a primary screen followed by complementary CM assays chosen to enable mechanism-appropriate follow-up. The combined approach will enhance testing for CV liabilities prior to traditional in vivo models. PMID- 25134466 TI - Brain-targeted delivery of docetaxel by glutathione-coated nanoparticles for brain cancer. AB - Gliomas are some of the most aggressive types of cancers but the blood-brain barrier acts as an obstacle to therapeutic intervention in brain-related diseases. The blood-brain barrier blocks the permeation of potentially toxic compounds into neural tissue through the interactions of brain endothelial cells with glial cells (astrocytes and pericytes) which induce the formation of tight junctions in endothelial cells lining the blood capillaries. In the present study, we characterize a glutathione-coated docetaxel-loaded PEG-PLGA nanoparticle, show its in vitro drug release data along with cytotoxicity data in C6 and RG2 cells, and investigate its trans-blood-brain barrier permeation through the establishment of a Transwell cellular co-culture. We show that the docetaxel-loaded nanoparticle's size enables its trans-blood-brain barrier permeation; the nanoparticle exhibits a steady, sustained release of docetaxel; the drug is able to induce cell death in glioma models; and the glutathione coated nanoparticle is able to permeate through the Transwell in vitro blood brain barrier model. PMID- 25134469 TI - Using Bayesian hierarchical parameter estimation to assess the generalizability of cognitive models of choice. AB - To be useful, cognitive models with fitted parameters should show generalizability across time and allow accurate predictions of future observations. It has been proposed that hierarchical procedures yield better estimates of model parameters than do nonhierarchical, independent approaches, because the formers' estimates for individuals within a group can mutually inform each other. Here, we examine Bayesian hierarchical approaches to evaluating model generalizability in the context of two prominent models of risky choice cumulative prospect theory (Tversky & Kahneman, 1992) and the transfer-of attention-exchange model (Birnbaum & Chavez, 1997). Using empirical data of risky choices collected for each individual at two time points, we compared the use of hierarchical versus independent, nonhierarchical Bayesian estimation techniques to assess two aspects of model generalizability: parameter stability (across time) and predictive accuracy. The relative performance of hierarchical versus independent estimation varied across the different measures of generalizability. The hierarchical approach improved parameter stability (in terms of a lower absolute discrepancy of parameter values across time) and predictive accuracy (in terms of deviance; i.e., likelihood). With respect to test-retest correlations and posterior predictive accuracy, however, the hierarchical approach did not outperform the independent approach. Further analyses suggested that this was due to strong correlations between some parameters within both models. Such intercorrelations make it difficult to identify and interpret single parameters and can induce high degrees of shrinkage in hierarchical models. Similar findings may also occur in the context of other cognitive models of choice. PMID- 25134471 TI - Susceptible to distraction: children lack top-down control over spatial attention capture. AB - Considerable evidence has indicated that adults can exert top-down control to avoid distraction by salient-but-irrelevant stimuli. However, relatively little research has explored how this ability develops across the lifespan. In the present study, we therefore assessed how well children can control the capture of spatial attention. Children (M age = 4.2 years) and adults (M age = 21.5 years) searched for target "spaceships" of a specific color while trying to ignore salient precues that either matched or mismatched the target spaceship color. The results demonstrated that children are, in fact, more vulnerable to capture by irrelevant stimuli than are adults, even after accounting for children's overall cognitive slowing. PMID- 25134472 TI - Letter from the editor. PMID- 25134470 TI - Consciousness is not necessary for visual feature binding. AB - When visual information enters the brain, it is relayed to different specialized regions, processing features such as shape, color, or motion. And yet, in our conscious experience of a colored, moving shape, all the different features seem to be integrated into one unified percept. Therefore, it has been hypothesized that consciousness and feature binding share an intimate relationship. To study this relationship, we used a paradigm in which the behavioral effects of feature binding can be measured. Using masks, we investigated whether spontaneous binding between the orientation and location of a Gabor patch takes place when the Gabor patch is processed consciously or unconsciously. The results of our study suggest that orientation and location of a visually presented object are automatically integrated, even when subjects are unaware of that object. We conclude that binding and consciousness share a less intimate relationship than previously hypothesized, since consciousness is not a necessary condition for binding to occur. PMID- 25134473 TI - Integrase Strand Transfer Inhibitors in HIV Therapy. AB - HIV drug resistance has been one of the major obstacles to HIV eradication and has contributed to the need for the constant development of new antiretroviral drugs over the past 25 years. With the recent approval of dolutegravir for human therapy by the U.S. Food and Drug Administration, health practitioners may soon have access to three integrase strand transfer inhibitors to treat individuals living with HIV. Here, we review the use of raltegravir, elvitegravir, and dolutegravir for use in first- and second-line HIV treatment regimens and the issue of HIV resistance against integrase inhibitors. PMID- 25134475 TI - Cobicistat: a Novel Pharmacoenhancer for Co-Formulation with HIV Protease and Integrase Inhibitors. AB - Human immunodeficiency virus (HIV) therapy has evolved over the last 20 years from mono-drug therapy given five times daily to regimens consisting of three or four drugs combined in a single-tablet dosed once daily. To allow once-daily administration, several drugs require pharmacokinetic boosting by a concomitantly administered P-glycoprotein and cytochrome P450 inhibitor such as ritonavir. The availability of cobicistat provides an alternative to ritonavir to those who are intolerant to this drug, and the opportunity for co-formulated single-tablet regimens consisting of tenofovir/emtricitabine, cobicistat and elvitegravir, atazanavir or darunavir. The cobicistat/elvitegravir-based regimen is well tolerated and patients achieved high rates of HIV RNA suppression in clinical trials. Cobicistat inhibits renal tubular secretion of creatinine, resulting in increased serum creatinine concentrations and reduced estimated glomerular filtration rate, with a new set point reached after 4 weeks. Treatment limiting renal toxicity with cobicistat/elvitegravir and tenofovir disoproxil fumarate is infrequent and may be further reduced when cobicistat is co-formulated with tenofovir alafenamide fumarate, a novel formation of tenofovir currently undergoing clinical trials. PMID- 25134474 TI - Ceftaroline fosamil: a brief clinical review. AB - Ceftaroline is a novel cephalosporin with a favorable tolerability profile and broad in vitro activity against many resistant Gram-positive and common Gram negative organisms. Ceftaroline fosamil is the first cephalosporin to be approved by the United States Food and Drug Administration (FDA) for the treatment of adults with acute bacterial skin and soft tissue infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It is also approved by the FDA for the treatment of adults with community-acquired bacterial pneumonia, including cases caused by Streptococcus pneumoniae (with or without concurrent bacteremia), although there are no data at this time to support the use of ceftaroline fosamil for the treatment of pneumonia caused by MRSA. Ceftaroline fosamil is likewise approved by the European Commission for the treatment of adults with complicated skin and soft tissue infections or community acquired pneumonia. This review summarizes the pharmacokinetic and microbiologic properties of ceftaroline, as well as the safety and efficacy data that led to its approval by the FDA in 2010 and the European Commission in 2012. Future directions to be addressed are also highlighted. PMID- 25134476 TI - A Review of the Evidence for Using Bedaquiline (TMC207) to Treat Multi-Drug Resistant Tuberculosis. AB - Existing therapies for multi-drug resistant tuberculosis (MDR-TB) have substantial limitations, in terms of their effectiveness, side-effect profile, and complexity of administration. Bedaquiline is a novel diarylquinoline antibiotic that has recently been investigated as an adjunct to existing therapies for MDR-TB. Currently, limited clinical data are available to evaluate the drug's safety and effectiveness. In two small randomized-controlled clinical studies, bedaquiline given for 8 or 24 weeks has been shown to improve surrogate microbiological markers of treatment response, but trials have not yet evaluated its impact on clinical failure and relapse. Safety concerns include an increased mortality in the bedaquiline arm of one study, an increased incidence of QT segment prolongation on electrocardiogram, and hepatotoxicity. Until further research data are available, the use of bedaquiline should be confined to settings where carefully selected patients can be closely monitored. PMID- 25134477 TI - Japanese B Encephalitis: An Overview of the Disease and Use of Chimerivax-JE as a Preventative Vaccine. AB - The Japanese encephalitis virus (JEV) is endemic in many countries in southern Asia and the western Pacific Rim, with new spread to previously unrecognized countries. It is an important cause of childhood neurological disease associated with permanent neurological sequelae and death. Fortunately, JE is a vaccine preventable disease. The ChimeriVaxTM-JE (Sanofi Pasteur, Lyon, France) is a live attenuated chimeric vaccine derived from the live-attenuated yellow fever virus, YF17D, which expresses the envelope proteins of the attenuated JEV vaccine strain, SA14-14-2. It is a safe, well-tolerated vaccine that is highly immunogenic in adults and children. The average geometric mean neutralizing antibody titer (GMT) in adults is 1,392 and over 90% of adults remain seroprotected 5 years after vaccination. In children and toddlers, more than 80% remain seroprotected 2 years after primary vaccination and demonstrate a robust and durable anamnestic response (>500-fold rise in GMT) with 99.1% seroprotection rates 1 year after a booster vaccine dose. The ChimeriVaxTM-JE is effective in children living in endemic regions where the vaccine could possibly be integrated into existing childhood vaccination programs. ChimeriVaxTM-JE is also indicated for travelers at risk of JE infection. PMID- 25134479 TI - The problems with polio: toward eradication. AB - The global health effort to eradicate poliomyelitis (polio) has encountered a number of unforeseen and unpredictable challenges. This article provides a timely review of progress made toward eradication, including the polio vaccines in use, and explores the reasons for delays in eradication target dates. It provides an overview of some of the remaining barriers to eradication and looks toward overcoming these through the Polio Eradication and Endgame Strategic Plan. PMID- 25134478 TI - The Role of Human Beta-Defensin-2 in Pseudomonas aeruginosa Pulmonary Infection in Cystic Fibrosis Patients. AB - Cystic fibrosis (CF) is the most common genetic disease affecting the Caucasian population. Chronic Pseudomonas aeruginosa pulmonary infection is the major cause of morbidity and mortality in CF patients. Human beta-defensin-2 (hBD-2) is an inducible pulmonary antimicrobial peptide that exerts bacteriostatic activity in a concentration-dependent manner. The decreased expression and compromised function of hBD-2 contributes to the pathogenesis of P. aeruginosa infection in the CF lung. The purpose of this review is to outline the significance of hBD-2 in P. aeruginosa chronic pulmonary infection in CF patients. PMID- 25134480 TI - Is Community-Acquired Methicillin-Resistant Staphylococcus aureus Coverage Needed for Cellulitis? AB - Methicillin-resistant Staphylococcus aureus (MRSA) has become the dominant strain of Staphylococcus aureus in many communities of the United States. As a result, many clinicians are now empirically covering for this pathogen in the treatment of various skin and soft-tissue infections. Should this practice apply to cellulitis? In order to answer this question, we defined cellulitis and reviewed the pathogenesis, microbiology, and current studies of inpatient and outpatient antimicrobial therapy. The current evidence suggests empirical MRSA coverage for community-acquired cellulitis may not be necessary in non-purulent (non suppurative) forms of this infection. Most cases are non-purulent and not amenable to culture although antibody studies indicate streptococci are the most common etiologic agents. Current studies of antimicrobial therapy tend to agree with this finding. Empirical beta-lactam therapy directed primarily at streptococci appears sufficient for non-purulent cellulitis regardless of the prevalence of MRSA in the community. PMID- 25134482 TI - Comparative Incidence of Nephrotoxicity by Age Group among Adult Patients Receiving Vancomycin. AB - INTRODUCTION: Little is known regarding age-related risk of nephrotoxicity during vancomycin therapy after the publication of the 2009 vancomycin consensus guidelines for therapeutic drug monitoring. We sought to evaluate incidence and risk factors for acute kidney injury in three age groups. METHODS: Matched cohort study of patients receiving vancomycin, grouped by age: young adults (18-64 years), older adults (65-79 years) and very elderly (>=80 years), matched on previously published risk factors for nephrotoxicity. Outcomes included traditional vancomycin nephrotoxicity and Acute Kidney Injury Network-modified definition of nephrotoxicity. RESULTS: The incidence of acute kidney injury was 34.1% vs. 34.1% vs. 31.8% in the young, older adults and very elderly groups, respectively (p = 0.97). In the logistic regression model, after adjusting for baseline risk factors, age was not a significant predictor of acute kidney injury. Lower respiratory tract infection (adjusted odds ratio [aOR] 5.18; 95% confidence interval [CI] 2.15-12.41) and duration of treatment (aOR 1.12; 95% CI 1.03-1.22) were found to be independently associated with outcome. CONCLUSION: No differences in risk of acute kidney injury were identified between young, older, and very elderly adults when adjusting for other risk factors. Further research is required to identify strategies to optimize the safety of vancomycin in the aging population. PMID- 25134483 TI - Stable susceptibility to aminoglycosides in an age of low level, institutional use. AB - INTRODUCTION: The use of aminoglycosides has decreased dramatically over several decades in the United States due to the introduction of safer Gram-negative agents. This study was conducted to assess possibly changing aminoglycoside susceptibility rates between 2006 and 2012 and in reference to 1992 use in the context of aminoglycoside use volume. METHODS: Quarterly adult use of amikacin, gentamicin and tobramycin were determined from the Medical University of South Carolina Medical Center, Charleston, South Carolina, USA, pharmacy drug use database and expressed as total aminoglycoside defined daily doses per 1,000 patient days for the years 1992 and 2006 through 2012. Annual susceptibility of Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, for the years 1992, 2006, and 2008 through 2012 were retrieved from our hospital's clinical microbiology database (duplicate isolates were excluded). Quarterly and annualized aminoglycoside usage rates were compared to the other years of interest. Likewise, susceptibility rates of the target organisms to each aminoglycoside were also compared across the same timeframe. RESULTS: While total use of aminoglycosides decreased slightly from 1992 to 2006, it increased by about 40% between 2006 and 2008 and then stabilized. Changes in susceptibility rates between 1992 and 2006 were all <=+/-9% with the exception of K. pneumoniae susceptibility to amikacin (-17%). Changes in susceptibility from 1992 to 2012 were also all <=+/-9%. Tobramycin remained the most active versus P. aeruginosa (% susceptible = 90), while amikacin remained most active versus E. coli and K. pneumoniae (% susceptible = 98 and 98, respectively). CONCLUSION: With low level use of aminoglycosides in our institution over the past 2 decades, the susceptibility of key Gram-negative pathogens has remained relatively stable, preserving these agents as potential alternative therapies as resistance arises to other frequently used antibiotics. PMID- 25134481 TI - Evaluation of Daptomycin Non-Susceptible Staphylococcus aureus for Stability, Population Profiles, mprF Mutations, and Daptomycin Activity. AB - INTRODUCTION: Despite studies examining daptomycin non-susceptible (DNS) Staphylococcus aureus, examination of the stability and population profiles is limited. The objective was to evaluate the stability, population profiles, and daptomycin activity against DNS isolates. METHODS: The stability of 12 consecutive clinical DNS strains was evaluated by minimum inhibitory concentration (MICs) and population analysis profiles before and after 5 days of serial passage. Two pairs of DNS S. aureus having the same daptomycin MIC but different daptomycin population profiles were evaluated via an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial vegetations for 96 h against daptomycin 6 and 10 mg/kg/day. The sequence of mprF was determined for these isolates before and after 96 h of daptomycin exposure in the in vitro PK/PD model. RESULTS: Daptomycin MIC values were 2-4 mg/L (via Microscan) for the 12 clinical isolates; 9 were confirmed DNS and 3 were within 1 tube dilution of Microscan (daptomycin MIC 1 mg/L). All were stable to serial passage. There was variation in the isolates susceptibility to daptomycin on population analysis (daptomycin population AUC 14.01-26.85). The killing patterns of daptomycin 6 and 10 mg/kg/day differed between isolates with a left-shift and right-shift population profile to daptomycin. Two strains developed additional mprF mutations during daptomycin exposure in the in vitro PK/PD model resulting in P314L, L826F, S337L and a novel Q326Stop mutation. CONCLUSIONS: The collection of DNS isolates was stable and displayed variation in susceptibility to daptomycin on population profile. Further research examining this clinical relevance is warranted. PMID- 25134484 TI - Amikacin pharmacokinetics during continuous veno-venous hemodialysis. AB - INTRODUCTION: Little is known about the pharmacokinetics of amikacin during continuous renal replacement therapy. METHODS: This prospective observational study included patients admitted to an academic medical center who received amikacin therapy while on continuous veno-venous hemodialysis (CVVHD) and had at least two serum sample concentrations measured after first-dose administration. First-order pharmacokinetic parameters, patient characteristics, and CVVHD parameters were recorded. RESULTS: Fifteen patients were included in the analysis. The median (interquartile range) dose of amikacin and dialysate flow rate, based on adjusted body weight, were 14.1 mg/kg (11.7-17.3 mg/kg) and 23.9 mL/kg/h (19.0-29.5 mL/kg/h), respectively. This corresponded with a median C max of 28.5 MUg/mL (20.9-39.0 MUg/mL). There was a significant correlation between clearance and dialytic dose (for every 1 L/h increase in dialysate flow rate, clearance rate increased by 23.6 mL/min [95% confidence interval 1.7-45.4 mL/min; P = 0.037]). CONCLUSION: The results of this study suggest that amikacin dose and interval should be individualized for each patient on CVVHD based on first-dose pharmacokinetic assessment. PMID- 25134485 TI - Erratum to: Low Specificity of a Malaria Rapid Diagnostic Test During an Integrated Community Case Management Trial. PMID- 25134486 TI - Divergent total synthesis of 1,6,8a-tri-epi-castanospermine and 1-deoxy-6,8a-di epi-castanospermine from substituted azetidin-2-one (beta-lactam), involving a cascade sequence of reactions as a key step. AB - A divergent, short, and novel total synthesis of 1,6,8a-tri-epi-castanospermine (7) and 1-deoxy-6,8a-di-epi-castanospermine (8) has been developed via a common precursor, 15, obtained from D-mannitol derived beta-lactam. The key step involves a one pot cascade sequence of trimethyl sulfoxonium ylide based cyclization of epoxy sulfonamide 14via epoxide ring opening, one carbon homologation followed by intramolecular cyclization. PMID- 25134487 TI - Computational mitral valve evaluation and potential clinical applications. AB - The mitral valve (MV) apparatus consists of the two asymmetric leaflets, the saddle-shaped annulus, the chordae tendineae, and the papillary muscles. MV function over the cardiac cycle involves complex interaction between the MV apparatus components for efficient blood circulation. Common diseases of the MV include valvular stenosis, regurgitation, and prolapse. MV repair is the most popular and most reliable surgical treatment for early MV pathology. One of the unsolved problems in MV repair is to predict the optimal repair strategy for each patient. Although experimental studies have provided valuable information to improve repair techniques, computational simulations are increasingly playing an important role in understanding the complex MV dynamics, particularly with the availability of patient-specific real-time imaging modalities. This work presents a review of computational simulation studies of MV function employing finite element structural analysis and fluid-structure interaction approach reported in the literature to date. More recent studies towards potential applications of computational simulation approaches in the assessment of valvular repair techniques and potential pre-surgical planning of repair strategies are also discussed. It is anticipated that further advancements in computational techniques combined with the next generations of clinical imaging modalities will enable physiologically more realistic simulations. Such advancement in imaging and computation will allow for patient-specific, disease-specific, and case specific MV evaluation and virtual prediction of MV repair. PMID- 25134488 TI - Hypothalamic pituitary dysfunction amongst nasopharyngeal cancer survivors. AB - PURPOSE: Radiation fields for nasopharyngeal cancer (NPC) include the base of skull, which places the hypothalamus and pituitary at risk of damage. We aimed to establish the prevalence, pattern and severity of hypothalamic pituitary (HP) dysfunction amongst NPC survivors. METHODS: We studied 50 patients (31 males) with mean age 57 +/- 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function. RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01. CONCLUSION: Despite low awareness and detection rates, HP dysfunction post NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors. PMID- 25134489 TI - A novel AMPK activator reduces glucose uptake and inhibits tumor progression in a mouse xenograft model of colorectal cancer. AB - The anticancer activity of a novel pure 1,4-Diaryl-2-azetidinone (1), endowed with a higher solubility than the well known Combretastatin A4, is tested in mice. We previously reported that Compound (1) showed specific antiproliferative activity against duodenal and colon cancer cells, inducing activation of AMP activated protein kinase and apoptosis. Here we estimate that the maximum tolerated dose in a mouse model is 40 mg/kg; the drug is well tolerated both in single dose and in repeated administration schedules. The drug displays a significant antitumor activity and a tumor growth delay when administered at the MTD both in single and fractionated i.v. administration in a mouse xenograft model of colorectal cancer. Arrest of tumor growth and relapse after drug suspension are parallel to modification in glucose demand as shown by PET studies with [(18)F] FDG. These data strongly support Compound (1) as a promising molecule for in vivo treatment of colorectal cancer. PMID- 25134491 TI - In situ SERS detection of emulsifiers at lipid interfaces using label-free amphiphilic gold nanoparticles. AB - Herein, we fabricated amphiphilic gold nanoparticles (GNPs) that can self assemble at oil-water interfaces. We applied those GNPs for in situ SERS detection of emulsifier molecules within the interfacial region of oil in water (O/W) emulsion systems. PMID- 25134490 TI - Mechanisms of beta-lactam antimicrobial resistance and epidemiology of major community- and healthcare-associated multidrug-resistant bacteria. AB - Alexander Fleming's discovery of penicillin heralded an age of antibiotic development and healthcare advances that are premised on the ability to prevent and treat bacterial infections both safely and effectively. The resultant evolution of antimicrobial resistant mechanisms and spread of bacteria bearing these genetic determinants of resistance are acknowledged to be one of the major public health challenges globally, and threatens to unravel the gains of the past decades. We describe the major mechanisms of resistance to beta-lactam antibiotics - the most widely used and effective antibiotics currently - in both Gram-positive and Gram-negative bacteria, and also briefly detail the existing and emergent pharmacological strategies to overcome such resistance. The global epidemiology of the four major types of bacteria that are responsible for the bulk of antimicrobial-resistant infections in the healthcare setting - methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Enterobactericeae, and Acinetobacter baumannii - are also briefly described. PMID- 25134492 TI - Analysis of spontaneous pneumothorax in the city of Cuneo: environmental correlations with meteorological and air pollutant variables. AB - BACKGROUND AND PURPOSE: Primary spontaneous pneumothorax (PSP) tends to cluster. Previous studies have found a correlation between PSP and atmospheric pressure variations or thunderstorms. We conducted this study to analyze the PSP correlations with meteorological variables and the concentrations of air pollutants in the city of Cuneo in Italy (IT). METHODS: We evaluated prospectively 451 consecutive PSP patients treated between 2004 and 2010. For each day within the period analyzed, the meteorological parameters and pollutants data were recorded. Statistical analyses on PSP were done for distribution characteristics, spectral autocorrelation, and spectral analysis. Multivariate regression analyses were performed using artificial neural networks. RESULTS: Analysis of annual, seasonal, and monthly distributions showed no significant correlation between PSP and the time series. The spectral analysis showed that PSP events were not random. Correlations between meteorological and environmental variables confirmed that PSP was significantly more likely to occur on warm windy days with high atmospheric pressure and high mean nitrogen dioxide concentration. CONCLUSIONS: Meteorological parameters and atmospheric pollutants might explain the cluster onset of PSP. PMID- 25134493 TI - Ocular Pharmacokinetics of a Novel Loteprednol Etabonate 0.4% Ophthalmic Formulation. AB - INTRODUCTION: Topical ophthalmic formulations of corticosteroids are commonly used to treat a variety of ocular diseases and conditions that have an inflammatory component. The purpose of this study was to evaluate the effect of the mucus-penetrating particle (MPP) technology on the pharmacokinetic profile of loteprednol etabonate in the ocular tissues of rabbits. METHODS: Forty-eight New Zealand White rabbits were randomly assigned to two groups (n = 3 rabbits or 6 eyes per time point) and treated with either the novel loteprednol etabonate MPP suspension formulation, 0.4% (LE-MPP 0.4%), or the commercial Lotemax((r))-brand loteprednol etabonate ophthalmic suspension, 0.5% (Lotemax 0.5%) (Bausch & Lomb Incorporated, Inc., Rochester, NY, USA). Samples of aqueous humor, various ocular tissues, and plasma were collected from animals over a 12-h period after a single dose of the test articles. Loteprednol etabonate concentrations were assayed using liquid chromatography-tandem mass spectrometry (LC/MS/MS). RESULTS: Loteprednol etabonate was rapidly absorbed into ocular tissues following administration of either formulation. A higher ocular exposure was achieved using LE-MPP 0.4%, with peak concentrations of approximately threefold higher in ocular tissues and the aqueous humor than Lotemax 0.5%. CONCLUSIONS: Administration of LE-MPP 0.4% improved loteprednol etabonate pharmacokinetic profile in ocular tissues of rabbits. The results of this study support the premise that the MPP technology can be used to enhance ocular exposure for topically applied therapeutic agents. Further studies to assess the clinical efficacy and safety of the LE-MPP formulation are warranted. PMID- 25134494 TI - Historical Review and Update of Surgical Treatment for Corneal Endothelial Diseases. AB - The cornea remains in a state of deturgescence, maintained by endothelial cell Na+/K+ ATPase and by tight junctions between endothelial cells that limit entrance of fluid into the stroma. Fuchs' endothelial corneal dystrophy (FECD) was initially described by Fuchs in 1910 as a combination of epithelial and stromal edema in older patients. It manifests as bilateral, albeit asymmetric, central corneal guttae, corneal edema, and reduced vision. When edema is severe, the corneal epithelium can detach from its basement membrane, creating painful bullae on the anterior surface of the cornea. The course of this dystrophy can be further accelerated after intraocular surgery, specifically cataract extraction. Pseudophakic bullous keratopathy (PBK) is endothelial cell loss caused by surgery in the anterior chamber. If the corneal endothelium is damaged during surgery, the same spectrum of symptoms as found in FECD can develop. In the nineteenth century, penetrating keratoplasty was the only surgical procedure available for isolated endothelial disease. In the 1960s, Dr. Jose Barraquer described a method of endothelial keratoplasty using an anterior approach via laser-assisted in situ keratomileusis (LASIK) flap. In 1999, Melles and colleague described their technique of posterior lamellar keratoplasty. Later, Melles et al. started to change host dissection using simple "descemetorhexis" in a procedure known as Descemet's stripping endothelial keratoplasty. Following the widespread adoption of Descemet's stripping automated endothelial keratoplasty, the Melles group revisited selective Descemet's membrane transplantation and reported the results of a new procedure, Descemet's membrane endothelial keratoplasty (DMEK). Recently, some eye banks have experimented with the preparation of DMEK/Descemet's membrane automated endothelial keratoplasty donor tissue that may help the surgeon avoid the risk of tissue loss during the stromal separation step. Recently, the authors described a new bimanual technique for insertion and positioning of endothelium-Descemet membrane grafts in DMEK. PMID- 25134495 TI - Review of Systemic Immunosuppression for Autoimmune Uveitis. AB - The purpose of this review is to comprehensively examine the various therapeutic agents available to treat autoimmune eye disease, their indications, clinical safety and recent developments. The stepladder approach is reviewed, including corticosteroid administration of various forms, classic immunomodulators, and newer biologic response modifiers. The authors present that corticosteroid monotherapy is almost never curative and carries significant side effects, while immunomodulatory therapy, when used appropriately as way to induce steroid-free remission, carries far less risk of causing long-term complications and provides greater potential of altering the immune system to induce a durable remission. PMID- 25134496 TI - Antioxidants Improve the Viability of Stored Adult Retinal Pigment Epithelial-19 Cultures. AB - INTRODUCTION: There is increasing evidence that retinal pigment epithelium (RPE) can be used to treat age-related macular degeneration, one of the leading causes of blindness worldwide. However, the best way to store RPE to enable worldwide distribution is unknown. We investigated the effects of supplementing our previously published storage method with seven additives, attempting to improve the number of viable adult retinal pigment epithelial (ARPE)-19 cells after storage. MATERIALS AND METHODS: ARPE-19 cells were cultured on multiwell plates before being stored for 1 week at 16 degrees C. Unsupplemented Minimal Essential Medium (MEM) (control) and a total of seven individual additives (DADLE ([D Ala(2), D-Leu(5)]-encephalin), capsazepine, docosahexaenoic acid (DHA), resveratrol, quercetin, simvastatin and sulforaphane) at three to four concentrations in MEM were tested. The individual effect of each additive on cell viability was analyzed with a microplate fluorometer. Cell phenotype was investigated by both microplate fluorometer and epifluorescence microscopy, and morphology by scanning electron microscopy. RESULTS: Supplementation of the storage medium with DADLE, capsazepine, DHA or resveratrol significantly increased the number of viable cells by 86.1% +/- 41.9%, 67.9% +/- 24.7%, 36.5% +/- 10.3% and 21.1% +/- 6.4%, respectively, compared to cells stored in unsupplemented MEM. DHA and resveratrol significantly reduced caspase-3 expression, while expression of RPE65 was maintained across groups. CONCLUSION: The number of viable ARPE-19 cells can be increased by the addition of DADLE, capsazepine, DHA or resveratrol to the storage medium without perturbing apoptosis or differentiation. PMID- 25134497 TI - A randomized controlled longitudinal naturalistic trial testing the effects of automatic self transcending meditation on heart rate variability in late life depression: study protocol. AB - BACKGROUND: The prevalence and socioeconomic cost of late life depression (LLD) is on the rise, while the response rate to antidepressant trials remains poor. Various mind-body therapies are being embraced by patients as they are considered safe and potentially effective, yet little is known regarding the effectiveness of such therapies to improve LLD symptoms. Among the mind-body therapies currently in practice, the results of our pilot study have shown that a particular meditation technique called Sahaj Samadhi Meditation, which belongs to the category of meditation termed automatic self-transcending meditation (ASTM) may have some promise in improving cardiovascular autonomic disturbances associated with LLD as well as ameliorating symptoms of depression and anxiety. METHODS/DESIGN: Patients between the ages of 60 and 85 with LLD will be randomized either to ASTM plus treatment as usual (TAU) or TAU alone to assess changes in cardiovascular autonomic parameters, neuropsychological symptoms of depression and anxiety as well as quality of life. The instructional phase of the intervention consists of 4 consecutive days of meditation training, after which participants are encouraged to meditate twice daily for twenty minutes each time at home. The intervention also includes once weekly follow up sessions for the subsequent 11 weeks. The planned study has one and a half year recruitment period. Participants will be assessed at baseline and at 4, 8, 12 and 24 weeks post intervention. DISCUSSION: This study should provide a unique data source from a randomized, controlled, longitudinal trial to investigate the effects of a form of ASTM on cardiovascular autonomic and neuropsychological health in LLD. TRIAL REGISTRATION: Clinicaltrials.gov NCT02149810, date registered: 05/28/2014. PMID- 25134498 TI - Hurler syndrome: orofacial, dental, and skeletal findings of a case. AB - Hurler syndrome is a disorder of mucopolysaccharide metabolism caused due to inherited deficiencies of lysosomal alpha-l-iduronidase activity. We present a case of a 15-year-old male patient presenting with clinical and laboratory characteristics of the syndrome. A rare combination of skeletal, ophthalmologic, and dental findings was observed in this patient. Mucopolysaccharides excretion spot test of urine was positive and an assay of alpha-l-iduronidase enzyme was deficient, confirming the clinical diagnosis of Hurler syndrome. PMID- 25134499 TI - Evidence for a role of 5-HT2C receptors in the motor aspects of performance, but not the efficacy of food reinforcers, in a progressive ratio schedule. AB - RATIONALE: 5-Hydroxytryptamine2C (5-HT2C) receptor agonists reduce the breakpoint in progressive ratio schedules of reinforcement, an effect that has been attributed to a decrease of the efficacy of positive reinforcers. However, a reduction of the breakpoint may also reflect motor impairment. Mathematical models can help to differentiate between these processes. OBJECTIVE: The effects of the 5-HT2C receptor agonist Ro-600175 ((alphaS)-6-chloro-5-fluoro-alpha-methyl 1H-indole-1-ethanamine) and the non-selective 5-HT receptor agonist 1-(m chlorophenyl)piperazine (mCPP) on rats' performance on a progressive ratio schedule maintained by food pellet reinforcers were assessed using a model derived from Killeen's Behav Brain Sci 17:105-172, 1994 general theory of schedule-controlled behaviour, 'mathematical principles of reinforcement'. METHOD: Rats were trained under the progressive ratio schedule, and running and overall response rates in successive ratios were analysed using the model. The effects of the agonists on estimates of the model's parameters, and the sensitivity of these effects to selective antagonists, were examined. RESULTS: Ro 600175 and mCPP reduced the breakpoint. Neither agonist significantly affected a (the parameter expressing incentive value), but both agonists increased delta (the parameter expressing minimum response time). The effects of both agonists could be attenuated by the selective 5-HT2C receptor antagonist SB-242084 (6 chloro-5-methyl-N-{6-[(2-methylpyridin-3-yl)oxy]pyridin-3-yl}indoline-1 carboxamide). The effect of mCPP was not altered by isamoltane, a selective 5 HT1B receptor antagonist, or MDL-100907 ((+/-)2,3-dimethoxyphenyl-1-(2-(4 piperidine)methanol)), a selective 5-HT2A receptor antagonist. CONCLUSIONS: The results are consistent with the hypothesis that the effect of the 5-HT2C receptor agonists on progressive ratio schedule performance is mediated by an impairment of motor capacity rather than by a reduction of the incentive value of the food reinforcer. PMID- 25134501 TI - Effects of mixing alcohol with energy drink on objective and subjective intoxication: results from a Dutch on-premise study. AB - BACKGROUND: The purpose of this on-premise study was to determine if alcohol mixed with energy drink (AMED) consumption masks the subjective feelings of intoxication when compared to consuming alcohol only. METHODS: The study was conducted on five nights in the city center of Utrecht. N = 997 people leaving bars were interviewed about their alcohol consumption with and without energy drinks, for that particular evening and for other occasions. People reporting drug and medication use were excluded (N = 84). Subjective intoxication was rated on a 10-point scale. Objective intoxication (breath alcohol concentration, BrAC) was determined with a breath alcohol test. Three groups were identified: (1) the AMED-tonight group (N = 185, 20.2 %), (2) the AMED-other-nights group (N = 246, 27.1 %), and (3) the no-AMED group (N = 482, 52.7 %). RESULTS: Objective intoxication (BrAC) did not significantly differ (p = 0.94) between the AMED tonight group (0.074 % +/- 0.05), AMED-other-nights group (0.073 % +/- 0.05), and the no-AMED group (0.074 % +/- 0.05). In line, subjective intoxication was not significantly different (p = 0.96) between the AMED-tonight group (4.5 +/- 2.2), AMED-other-nights group (4.6 +/- 2.3), and no-AMED group (4.6 +/- 2.2). Within subjects comparisons revealed no significant differences in total alcohol consumption between AMED occasions and alcohol only occasions. Regression analyses showed that "gender" (beta = 0.078, p = 0.016), "time of testing" (beta = 0.085, p = 0.009,) and "BrAC" (beta = 0.574, p = 0.0001) together explained 37.7 % of variance of subjective intoxication scores (Cohen's f (2) = 0.605). Whether or not subjects consumed energy drinks did not predict subjective intoxication scores. CONCLUSION: The data suggests that mixing alcohol with energy drink does not mask subjective intoxication. PMID- 25134500 TI - Differential effects of dopamine D1 and D 2/3 receptor antagonism on motor responses. AB - RATIONALE: The zebrafish dopaminergic system is thought to be evolutionarily conserved and may be amenable to pharmacological manipulation using drugs developed for mammalian receptors. However, only few studies have examined the role of specific receptor subtypes in behaviour of adult zebrafish. OBJECTIVES: The objectives of this study are to determine the translational relevance of the zebrafish and examine the psychopharmacology of specific dopamine receptors in this species. METHODS: Using a behavioural pharmacological approach, we examine the effect of D1 and D2/3 receptor antagonisms on motor patterns of adult zebrafish during acute drug exposure and withdrawal. RESULTS: Acute exposure to SCH-23390 (D1 receptor antagonist) decreased total distance travelled in a dose dependent manner. Exposure to amisulpride (D2/3 receptor antagonist) induced a biphasic dose-response in total distance travelled and in angular velocity. The results provide support for the existence of structurally and functionally conserved postsynaptic D1 and D2 receptors, as well as presynaptic D2 autoreceptors in the zebrafish brain. The behavioural effects of the employed antagonists did not persist following 30 min of withdrawal. CONCLUSION: The results suggest that zebrafish, a cheaper and simpler model organism compared to the rat and the mouse, may be an efficient translationally relevant tool for the analysis of the psychopharmacology of receptors of the vertebrate dopaminergic system. PMID- 25134503 TI - [Editorial: Nursing and health care reform]. PMID- 25134502 TI - Behavioral effects of glucocorticoids during the first exposures to the forced swim stress. AB - RATIONALE: Glucocorticoids facilitate coping with stress, but their high levels have been also implicated in mood disorders. Due to this duality, the role of glucocorticoid signaling in the development of the first episodes of stress induced depression remains unclear. OBJECTIVES: To address this issue, effects of the glucocorticoid signal modulation on depressive-like behavior during pretest and test Porsolt swim sessions were examined. METHODS: Metyrapone (MET; 150 mg/kg, i.p.) was injected 3 h before pretest to block stress-induced increase in corticosterone levels. Dexamethasone (DEX; 0.2 mg/kg, s.c.) was applied to MET treated rats 1 h before both pretest and test sessions. In addition to behavior during these sessions, glucocorticoid receptor (GR) expression was analyzed by immunohistochemistry 2 h after the second swim. RESULTS: In pretest, MET-treated rats exhibited increased latency to immobility and shortened immobility. DEX reversed the behavioral effects of MET in the pretest. In the test, animals from MET + DEX group unexpectedly exhibited an antidepressant-like behavior. Swim stress increased GR expression in the frontal cortex irrespective of the pharmacological treatment. A significant elevation in GR expression was found in the prefrontal cortex (PFC) of stressed MET + DEX-treated rats and in the PFC of unstressed rats 6 h after injection of DEX alone. CONCLUSION: The data suggest that the increase in glucocorticoid levels under swim stress during pretest directly contributes to the development of the immobility response. Transition of DEX effect from prodepressant in the pretest to an antidepressant in the test was associated with the elevation in the PFC GR expression. PMID- 25134505 TI - [Mission woman: a survey on the perception of the "Service of Welcome and Listening" offered in the Emergency Department at the San Camillo Hospital in Rome by women victims of violence]. AB - INTRODUCTION: The project Mission Woman was set up to describe how the service offered by the Emergency Department of the Hospital San Camillo-Forlanini in Rome was perceived by women victims ( or supposed to be) of violence. The objective of this investigation is to frame clients' perception about the service offered by staff in terms of sensitivity, recognition and management of the issue. The access to the Emergency Room is the first contact of the client with a helping relationship which goes beyond the simple provision of medical care. METHODS: A questionnaire devised for the purpose was filled in by women who have asked for help to the Service "Door Woman" . The Service "Door Woman", set up in 2009, aimed to welcome and listen women victims of violence with the collaboration of different operators in the emergency department: nurses, doctors, psychologists and social workers. The project developed within the Hospital S. Camillo Forlanini is managed by both professionals of the Emergency Department together with the Charity "Be Free". The service is open 24/7, all year, the clients could be women or children and could receive assistance or medical, nursing, psychosocial and legal counselling. The triage nurses are those who through their expertise could first identify the victims of violence and to introduce them in the path. CONCLUSION: Despite the level of injuries, who access to the Emergency Room for single or repeated events of violence, may have decided to claim in court and not hide seeking.. The research aims to understand what are the theoretical and practical deficiencies of staff in the management of a issue which is not only medical but also social and legal, as well as structural and organizational weaknesses of the service. PMID- 25134504 TI - [Waiting time between acute event and rehabilitation: continuity of nursing care and rehabilitation. Analysis and suggestions for a Service of Protected Discharge]. AB - INTRODUCTION: In recent years, in Italy, population lengthening of life leads to an higher number of individuals with chronic diseases (Osservatorio, 2010). The hospital which deals with the acute phase of diseases needs to be integrated with primary care. This connection is particularly important for the treatment, care and rehabilitation of patient, as well as a general need for more health and social care integrated tools. OBJECTIVE: At the San Gerardo Hospital in Monza, in the context of the patient's post-acute rehabilitation, we analyze the phase between discharge from hospital and the expected date of hospitalization in facilities providing rehabilitation. The aim of this observational descriptive study is to determine the distribution of days of waiting. Furthermore, several different approach are analysed (i.e. Integrated Home Care) in order to reduce unnecessary days hospitalization and a more intelligent and cost effective use of resources The research question are the follow, to quantify waiting time between discharge and hospitalization in the rehabilitation facility and to ascertain if patients are sent to the correct facility. RESULT: 1083 individuals were taken into account, of those 55% (N=652) were discharged from the hospital later. This leads to a 4505 days of inappropriate hospitalization. CONCLUSION: Although the use of home care could be beneficial to the hospital, this can be used only for tiny part of the patients and it is not cost effective. A possible solution can be set up a number of low cost bed entirely managed by nurses due to the low level of intensity care. PMID- 25134506 TI - [Profiles and evaluation process: what integration? Experience of the Local Health Agency TO2 of Turin]. AB - INTRODUCTION: The Service of Health Professions of this facility (TO2 of Turin) aimed during the 2010 to devise/develop a new evaluation tool for the new employees , trying to fit them with the profiles set up the previous year. METHODS: The conceptual model of reference for the construction of working drafts of the grids was inspired by the special insert edition of "L'infermiere" in 2007, a literature review was carried out and a number of internal meeting within 6 of the Service of health Professions were set up. A working group were set up - 93 people - as well as indicators were developed to monitor and implementation of the instruments. Once the drafts of the standard tools were made, working groups started to improve the tools provided under the supervision of a tutor. Finally half way through an evaluation was carried out using a questionnaire. CONCLUSION: The new template leads a number of problems which were later sorted out also with the support of tutors. PMID- 25134507 TI - [Scale Mosaic: definition and testing of a tool for assessing the risk of falling and the care planning during hospitalization]. AB - INTRODUCTION: in year 2008 the Ausl of Ravenna had a small number of patients at risk among the patients fallen, and among the patients evaluated with risk for fall. This could be due to the rating scale used (Conley) that does not recognize the risk factors "drug therapy" and "conditions clinical care". OBJECTIVES: to experiment a rating scale (Mosaic), to evaluate the performance indicators compared to the scales Conley, Fall Risk Assessment Scoring System (FRASS), Stratity; evaluate the effectiveness of actions taken to manage the risk; Operators remain vigilant about the risk falls. METHODOLOGY: using the scale Mosaic for patients admitted in 16 Hospital Units for two-months. Performance indicators: sensitivity, specificity, positive predictive value and negative. Studies considered for comparison: Hospital (AO) Bologna for Conley, AO Bologna and AO Niguarda Ca Granda Milan for Stratify, AO Bergamo for FRASS. RESULTS: were analyzed 1474 tabs. Males are 848 (57.5%) and females 626 (43.5%), the average age is 70.8 years. Of these 42 patients have fallen (2.8%), including 25 males and 17 females and the average age is 72.2. Are not at risk 426 (29%) patients and at risk 1048 (71%) patients. In other assessments the patients at risk was 31% in AUSL Ravenna, 59% (Conley) and 13% (Stratify) in AO Bologna and 41.5% (FRASS) in AO Bergamo. The scale Mosaic has a sensitivity of 0.98 (Conley, Stratify and FRASS amounted to 0.69, to 0.20, to 0.50), a specificity of 0.30 (Conley, Stratify and FRASS amounted to 0.41, 0.87, 0.59.) The patients fallen are at risk in 41 cases (97%) and of these 24 low-risk. The most frequent risk factors are: "mobility and gait" (1209 items), "drug therapy" (850 items) , "conditions clinical care" (841 items). Planned actions have an average of 2.2 in patients fallen, of 3.5 in low-risk patients and of 4.48 in patients at high risk. Compared with the previous year shows a decrease of 14 falls and an increase in the level of outcome "no one" (from 61% to 73.5%). DISCUSSION: the greater number of falls occur among low-risk patients, the average number of shares increases with increasing levels of risk and decreases in the patients fallen. Patients are at increased risk and therefore, in the hospital, it is essential to evaluate the factors drug therapy and conditions clinical care. The scale Mosaic has a very good performance for the sensitivity but not the specificity. The indicators in the studies are very different. This poses a reflection: what is the sense of the indicators when the rated instrument is part of a multifactorial prevention project whose implementation, usually, improves the level of security by preventing the occurrence of the event? Analysis of the tool can not be based only on numerical data. The true value of each scale is the level of attention that triggers in Health Care Workers, which activate preventive measures that allow an efficient management of risk. CONCLUSION: the card Mosaic has been adopted in Ausl because it improved the level of security of patients with risk of fall. PMID- 25134508 TI - [E-learning and university nursing education: an overview of reviews]. AB - INTRODUCTION: The increasing use of digital technologies and e-learning in nursing education and the health professions was also reflected in the time to many studies and reviews. The aim of this overview was to analyze education through e-learning technologies for nursing and health professional students. METHOD: A comprehensive search of literature was conducted using database PubMed/MEDLINE, Ebsco/CINAHL, 2003-2013. RESULT: The search strategy resulted in the inclusion, in first instance, of 9732 items. After the reduction of duplicates, applying limits and other parameters of inclusion/exclusion and, at the end, evaluation of quality through AMSTARD check list, we included in this overview, 22 reviews. The analized reviews were allowed to spread in different topic areas: study population (students and faculty), e-learning methods (blended learning Game/3D/situated learning) and evaluation (information technology, learning satisfaction comparison of e-learning with the traditional teaching methods) CONCLUSION: This overview demonstrates that e-learning in nursing academic education is a valid alternative to traditional learning. If e-learning activities are well structured and modulated, some advantages and economies are clear possible. Regard effects of e-learning on the improvement of ability, data are at the momenti limited when compared to traditional learning. Often e learning appear as an adjunct respect traditional learning, but is necessary consider e-learning and digital tecnology as priority for the future of education of nursing students. PMID- 25134509 TI - Clinical teaching models for nursing practice: a review of literature. AB - INTRODUCTION: Clinical placements provide opportunities for student nurses to learn experientially, thanks to clinical - practical teaching models. For this purpose this review wanted to better investigate the latest methods developed in nursing education to ameliorate the theory practice model in nursing education teaching model. METHODS: The review of the literature was performed through a search of nursing specific data bases, including Cinahl, Capsur, Ovid, Cockrane Library, PubMed from January 2010 to September 2012. It included key words, such as: Clinical Model; Nursing Education Model; Nursing Practical Teaching Model; Theory-Practice Model. RESULTS: A total of 8 articles were found. Of these, only 4 articles were considered for this review because they better analyzed one clinical teaching model in nursing practice. Each article was structured analyzed, by considering the "PICOS" method, with reference to participants, interventions, comparisons, outcomes, and study design. DISCUSSION: Four innovative clinical teaching models for nursing practice were considered: the first one was the Problem-Based Leaning method in nursing education; the second one was the Self-Regulated Learning strategy; the third one was the developing nursing students' reflective skills associated as a key component in the perceived coherence between theory and practice; the fourth one was the computer based clinical simulation. CONCLUSION: Each work performed an innovative clinical teaching model for nursing student. Some limitations were highlight, but all the literature revised emphasized the evaluation and feedback from students and the perceptions of their clinical activities is essential. PMID- 25134510 TI - Liver: a variant of FGF19 protects the liver from cholestatic injury without inducing cancer. PMID- 25134511 TI - Genetics of gastric cancer. AB - Gastric cancer remains highly prevalent and accounts for a notable proportion of global cancer mortality. This cancer is also associated with poor survival rates. Understanding the genetic basis of gastric cancer will offer insights into its pathogenesis, help identify new biomarkers and novel treatment targets, aid prognostication and could be central to developing individualized treatment strategies in the future. An inherited component contributes to <3% of gastric cancers; the majority of genetic changes associated with gastric cancer are acquired. Over the past few decades, advances in technology and high-throughput analysis have improved understanding of the molecular aspects of the pathogenesis of gastric cancer. These aspects are multifaceted and heterogeneous and represent a wide spectrum of several key genetic influences, such as chromosomal instability, microsatellite instability, changes in microRNA profile, somatic gene mutations or functional single nucleotide polymorphisms. These genetic aspects of the pathogenesis of gastric cancer will be addressed in this Review. PMID- 25134512 TI - Endoscopy: a window into the gut--real-time visualization of the effects of food intolerance using confocal laser endomicroscopy. PMID- 25134513 TI - Learning Style Scales: a valid and reliable questionnaire. AB - PURPOSE: Learning-style instruments assist students in developing their own learning strategies and outcomes, in eliminating learning barriers, and in acknowledging peer diversity. Only a few psychometrically validated learning style instruments are available. This study aimed to develop a valid and reliable learning-style instrument for nursing students. METHODS: A cross-sectional survey study was conducted in two nursing schools in two countries. A purposive sample of 156 undergraduate nursing students participated in the study. Face and content validity was obtained from an expert panel. The LSS construct was established using principal axis factoring (PAF) with oblimin rotation, a scree plot test, and parallel analysis (PA). The reliability of LSS was tested using Cronbach's alpha, corrected item-total correlation, and test-retest. RESULTS: Factor analysis revealed five components, confirmed by PA and a relatively clear curve on the scree plot. Component strength and interpretability were also confirmed. The factors were labeled as perceptive, solitary, analytic, competitive, and imaginative learning styles. Cronbach's alpha was >0.70 for all subscales in both study populations. The corrected item-total correlations were >0.30 for the items in each component. CONCLUSION: The LSS is a valid and reliable inventory for evaluating learning style preferences in nursing students in various multicultural environments. PMID- 25134514 TI - Cross-national validation of prognostic models predicting sickness absence and the added value of work environment variables. AB - PURPOSE: To validate Dutch prognostic models including age, self-rated health and prior sickness absence (SA) for ability to predict high SA in Danish eldercare. The added value of work environment variables to the models' risk discrimination was also investigated. METHODS: 2,562 municipal eldercare workers (95% women) participated in the Working in Eldercare Survey. Predictor variables were measured by questionnaire at baseline in 2005. Prognostic models were validated for predictions of high (>=30) SA days and high (>=3) SA episodes retrieved from employer records during 1-year follow-up. The accuracy of predictions was assessed by calibration graphs and the ability of the models to discriminate between high- and low-risk workers was investigated by ROC-analysis. The added value of work environment variables was measured with Integrated Discrimination Improvement (IDI). RESULTS: 1,930 workers had complete data for analysis. The models underestimated the risk of high SA in eldercare workers and the SA episodes model had to be re-calibrated to the Danish data. Discrimination was practically useful for the re-calibrated SA episodes model, but not the SA days model. Physical workload improved the SA days model (IDI = 0.40; 95% CI 0.19 0.60) and psychosocial work factors, particularly the quality of leadership (IDI = 0.70; 95% CI 053-0.86) improved the SA episodes model. CONCLUSIONS: The prognostic model predicting high SA days showed poor performance even after physical workload was added. The prognostic model predicting high SA episodes could be used to identify high-risk workers, especially when psychosocial work factors are added as predictor variables. PMID- 25134516 TI - Utilization of deletion bins to anchor and order sequences along the wheat 7B chromosome. AB - KEY MESSAGE: A total of 3,671 sequence contigs and scaffolds were mapped to deletion bins on wheat chromosome 7B providing a foundation for developing high resolution integrated physical map for this chromosome. Bread wheat (Triticum aestivum L.) has a large, complex and highly repetitive genome which is challenging to assemble into high quality pseudo-chromosomes. As part of the international effort to sequence the hexaploid bread wheat genome by the international wheat genome sequencing consortium (IWGSC) we are focused on assembling a reference sequence for chromosome 7B. The successful completion of the reference chromosome sequence is highly dependent on the integration of genetic and physical maps. To aid the integration of these two types of maps, we have constructed a high-density deletion bin map of chromosome 7B. Using the 270 K Nimblegen comparative genomic hybridization (CGH) array on a set of cv. Chinese spring deletion lines, a total of 3,671 sequence contigs and scaffolds (~7.8 % of chromosome 7B physical length) were mapped into nine deletion bins. Our method of genotyping deletions on chromosome 7B relied on a model-based clustering algorithm (Mclust) to accurately predict the presence or absence of a given genomic sequence in a deletion line. The bin mapping results were validated using three different approaches, viz. (a) PCR-based amplification of randomly selected bin mapped sequences (b) comparison with previously mapped ESTs and (c) comparison with a 7B genetic map developed in the present study. Validation of the bin mapping results suggested a high accuracy of the assignment of 7B sequence contigs and scaffolds to the 7B deletion bins. PMID- 25134517 TI - Spine-like nanostructured carbon interconnected by graphene for high-performance supercapacitors. AB - Recent studies on supercapacitors have focused on the development of hierarchical nanostructured carbons by combining two-dimensional graphene and other conductive sp(2) carbons, which differ in dimensionality, to improve their electrochemical performance. Herein, we report a strategy for synthesizing a hierarchical graphene-based carbon material, which we shall refer to as spine-like nanostructured carbon, from a one-dimensional graphitic carbon nanofiber by controlling the local graphene/graphitic structure via an expanding process and a co-solvent exfoliation method. Spine-like nanostructured carbon has a unique hierarchical structure of partially exfoliated graphitic blocks interconnected by thin graphene sheets in the same manner as in the case of ligaments. Owing to the exposed graphene layers and interconnected sp(2) carbon structure, this hierarchical nanostructured carbon possesses a large, electrochemically accessible surface area with high electrical conductivity and exhibits high electrochemical performance. PMID- 25134518 TI - Primary pulmonary myxoid sarcomas with EWSR1-CREB1 translocation might originate from primitive peribronchial mesenchymal cells undergoing (myo)fibroblastic differentiation. AB - Primary pulmonary myxoid sarcoma (PPMS) is a very rare lung tumor that has recently been shown to harbor an EWSR1-CREB1 translocation. However, the histogenesis and biological behavior of PPMS remains unclear. To provide insight into the histogenesis of PPMS, we studied surgical resection specimens of four patients, two females and two males with an age range of 26 to 65 years, all non smokers with mild anemia. The tumors, three of which are endobronchial, measured between 4 and 13 cm. One patient developed metastasis to the contra-lateral lung 7 months after resection. Other patients remained alive without tumor for 1.5, 10, and 13 years. Fluorescence in situ hybridization (FISH) analysis with a gene break apart probe showed an EWSR1 translocation in all cases. The EWSR1-CREB1 fusion transcript was detected in all cases by reverse-transcription PCR. Immunohistochemical staining showed diffuse positive staining of the tumor cells only for vimentin. Tumor cells expressed no other myoid, epithelial, endothelial, melanocytic, myoepithelial, or neuroendocrine markers, except for smooth muscle actin and epithelial membrane antigen, which were only focally positive in individual cases. Ultrastructural analyses revealed the presence in the tumor cells of intermediate filaments with focal densities along the sub-cytoplasmic membrane as well as dense plaques. These results suggest that PPMS exhibits myofibroblastic differentiation. We conclude that PPMS is an intermediate grade malignant lung tumor harboring EWSR1 translocations, which may originate from mesenchymal cells that undergo fibroblastic or myofibroblastic differentiation. PMID- 25134519 TI - Theoretical and experimental search for ZnSb-based thermoelectric materials. AB - We report a combined theoretical and experimental search for thermoelectric materials based on semiconducting zinc antimony. Influence of three new doping elements (sodium, potassium and boron) on the electronic properties was investigated as well as the carrier concentration and temperature dependence of the thermoelectric coefficients obtained through density-functional calculations and Boltzmann transport theory. Distortion of the electron arrangement caused by the doping elements is displayed as a deformation charge density around the atoms. Based on the band structures, the density of states, and the transport properties, we found that the presence of Na and K in the ZnSb matrix leads to a slightly improved p-type conductivity, whereas the B substitution leads to a n type doping. Because of the stronger need for obtaining n-type ZnSb-based material, the B(0.01)Zn(0.99)Sb structure has been transferred to the laboratory to be synthesized by direct melting. The sample was investigated using x-ray diffraction and scanning electron microscopy. PMID- 25134520 TI - Location-specific expression of chemokines, TNF-alpha and S100 proteins in a teat explant model. AB - The distal compartments of the udder are the first to interact with invading pathogens. The regulatory and effector functions of two major teat regions [Furstenberg's rosette (FR); teat cistern (TC)] are largely unknown. The objective of this study was to establish an in vitro model with explants of the FR and the TC to analyse their response towards Escherichia coli LPS and Staphylococcus aureus lipoteichoic acid (LTA). Quantitative stereological analysis confirmed differences in the cellular composition of FR and TC explants. Chemokine (CXCL8, CCL5, CCL20) and TNF-alpha mRNA were expressed at low levels in both locations. Explant stimulation with LPS increased the mRNA abundance of all tested chemokines and TNF-alpha. Stimulation with LTA only induced CCL20 and CXCL8. LPS- and LTA-stimulated explant supernatants contained CXCL8 and CXCL3. Supernatants significantly attracted neutrophils in vitro. Compared with TC, the FR showed high constitutive mRNA expression of S100 proteins (A8, A9, A12). In the TC, both LPS and LTA significantly induced S100A8, whereas S100A9 and S100A12 expression was only induced by LPS. The novel model system underpins the role of the teat for recognising pathogens and shaping a pathogen- and location-specific immune response. PMID- 25134515 TI - Specificity, propagation, and memory of pericentric heterochromatin. AB - The cell establishes heritable patterns of active and silenced chromatin via interacting factors that set, remove, and read epigenetic marks. To understand how the underlying networks operate, we have dissected transcriptional silencing in pericentric heterochromatin (PCH) of mouse fibroblasts. We assembled a quantitative map for the abundance and interactions of 16 factors related to PCH in living cells and found that stably bound complexes of the histone methyltransferase SUV39H1/2 demarcate the PCH state. From the experimental data, we developed a predictive mathematical model that explains how chromatin-bound SUV39H1/2 complexes act as nucleation sites and propagate a spatially confined PCH domain with elevated histone H3 lysine 9 trimethylation levels via chromatin dynamics. This "nucleation and looping" mechanism is particularly robust toward transient perturbations and stably maintains the PCH state. These features make it an attractive model for establishing functional epigenetic domains throughout the genome based on the localized immobilization of chromatin-modifying enzymes. PMID- 25134521 TI - Immunization with malondialdehyde-modified low-density lipoprotein (LDL) reduces atherosclerosis in LDL receptor-deficient mice challenged with Porphyromonas gingivalis. AB - Periodontal infections increase the risk of atherosclerotic vascular disease via partly unresolved mechanisms. Of the natural IgM Abs that recognize molecular mimicry on bacterial epitopes and modified lipid and protein structures, IgM directed against oxidized low-density lipoprotein (LDL) is associated with atheroprotective properties. Here, the effect of natural immune responses to malondialdehyde-modified LDL (MDA-LDL) in conferring protection against atherosclerosis, which was accelerated by the major periodontopathogen Porphyromonas gingivalis, was investigated. LDL receptor-deficient (LDLR(-/-)) mice were immunized with mouse MDA-LDL without adjuvant before topical application challenge with live P. gingivalis. Atherosclerosis was analyzed after a high-fat diet, and plasma IgG and IgM Ab levels were measured throughout the study, and the secretion of IL-5, IL-10 and IFN-gamma in splenocytes stimulated with MDA-LDL was determined. LDLR(-/-) mice immunized with MDA-LDL had elevated IgM and IgG levels to MDA-LDL compared with saline-treated controls. MDA-LDL immunization diminished aortic lipid depositions after challenge with P. gingivalis compared with mice receiving only P. gingivalis challenge. Immunization of LDLR(-/-) mice with homologous MDA-LDL stimulated the production of IL-5, implicating general activation of B-1 cells. Immune responses to MDA-LDL protected from the P. gingivalis-accelerated atherosclerosis. Thus, the linkage between bacterial infectious burden and atherogenesis is suggested to be modulated via natural IgM directed against cross-reactive epitopes on bacteria and modified LDL. PMID- 25134522 TI - Advancing the application of systems thinking in health: exploring dual practice and its management in Kampala, Uganda. AB - BACKGROUND: Many full-time Ugandan government health providers take on additional jobs - a phenomenon called dual practice. We describe the complex patterns that characterize the evolution of dual practice in Uganda, and the local management practices that emerged in response, in five government facilities. An in-depth understanding of dual practice can contribute to policy discussions on improving public sector performance. METHODS: A multiple case study design with embedded units of analysis was supplemented by interviews with policy stakeholders and a review of historical and policy documents. Five facility case studies captured the perspective of doctors, nurses, and health managers through semi-structured in-depth interviews. A causal loop diagram illustrated interactions and feedback between old and new actors, as well as emerging roles and relationships. RESULTS: The causal loop diagram illustrated how feedback related to dual practice policy developed in Uganda. As opportunities for dual practice grew and the public health system declined over time, government providers increasingly coped through dual practice. Over time, government restrictions to dual practice triggered policy resistance and protest from government providers. Resulting feedback contributed to compromising the supply of government providers and, potentially, of service delivery outcomes. Informal government policies and restrictions replaced the formal restrictions identified in the early phases. In some instances, government health managers, particularly those in hospitals, developed their own practices to cope with dual practice and to maintain public sector performance. Management practices varied according to the health manager's attitude towards dual practice and personal experience with dual practice. These practices were distinct in hospitals. Hospitals faced challenges managing internal dual practice opportunities, such as those created by externally-funded research projects based within the hospital. Private wings' inefficiencies and strict fee schedule made them undesirable work locations for providers. CONCLUSIONS: Dual practice prevails because public and private sector incentives, non-financial and financial, are complementary. Local management practices for dual practice have not been previously documented and provide learning opportunities to inform policy discussions. Understanding how dual practice evolves and how it is managed locally is essential for health workforce policy, planning, and performance discussions in Uganda and similar settings. PMID- 25134524 TI - Steps per Day, Daily Peak Stepping Cadence, and Walking Performance in Older Adults. AB - We tested the hypothesis that the intensity of daily ambulation would relate with functional walking capacity in older adults. Forty-three women (n = 25) and men (n = 18) between the ages of 60-78 years wore an accelerometer for measurement of average daily steps and 30-min peak stepping cadence. A 400-m walk test was used to measure walking speed. No sex difference was found for average daily steps (p = .76), average peak cadence (p = .96), or walking speed (p = .89). Daily steps (women: r = .68, p < .01; men: r = .04) and peak cadence (women: r = .81, p < .01; men: r = -.16) were positively correlated with walking speed in women but not in men. After controlling for daily steps, peak cadence remained significantly associated with walking speed in women (partial r = .61, p < .01). Walking intensity during daily ambulation is independently related to functional walking capacity in older adults, albeit this relation may be more significant for women than men. PMID- 25134525 TI - Skeletal muscle work efficiency with age: the role of non-contractile processes. AB - Although skeletal muscle work efficiency probably plays a key role in limiting mobility of the elderly, the physiological mechanisms responsible for this diminished function remain incompletely understood. Thus, in the quadriceps of young (n=9) and old (n=10) subjects, we measured the cost of muscle contraction (ATP cost) with 31P-magnetic resonance spectroscopy (31P-MRS) during (i) maximal intermittent contractions to elicit a metabolic demand from both cross-bridge cycling and ion pumping and (ii) a continuous maximal contraction to predominantly tax cross-bridge cycling. The ATP cost of the intermittent contractions was significantly greater in the old (0.30+/-0.22 mM.min-1.N.m-1) compared with the young (0.13+/-0.03 mM.min-1.N.m-1, P<0.05). In contrast, at the end of the continuous contraction protocol, the ATP cost in the old (0.10+/-0.07 mM.min-1.N.m-1) was not different from the young (0.06+/-0.02 mM.min-1.N.m-1, P=0.2). In addition, the ATP cost of the intermittent contractions correlated significantly with the single leg peak power of the knee-extensors assessed during incremental dynamic exercise (r=-0.55; P<0.05). Overall, this study reveals an age-related increase in the ATP cost of contraction, probably mediated by an excessive energy demand from ion pumping, which probably contributes to both the decline in muscle efficiency and functional capacity associated with aging. PMID- 25134523 TI - Transcriptome sequencing of a chimaera reveals coordinated expression of anthocyanin biosynthetic genes mediating yellow formation in herbaceous peony (Paeonia lactiflora Pall.). AB - BACKGROUND: Herbaceous peony (Paeonia lactiflora Pall.) is a traditional flower in China and a wedding attractive flower in worldwide. In its flower colour, yellow is the rarest which is ten times the price of the other colours. However, the breeding of new yellow P. lactiflora varieties using genetic engineering is severely limited due to the little-known biochemical and molecular mechanisms underlying its characteristic formation. RESULTS: In this study, two cDNA libraries generated from P. lactiflora chimaera with red outer-petal and yellow inner-petal were sequenced using an Illumina HiSeqTM 2000 platform. 66,179,398 and 65,481,444 total raw reads from red outer-petal and yellow inner-petal cDNA libraries were generated, which were assembled into 61,431 and 70,359 Unigenes with an average length of 628 and 617 nt, respectively. Moreover, 61,408 non redundant All-unigenes were obtained, with 37,511 All-unigenes (61.08%) annotated in public databases. In addition, 6,345 All-unigenes were differentially expressed between the red outer-petal and yellow inner-petal, with 3,899 up regulated and 2,446 down-regulated All-unigenes, and the flavonoid metabolic pathway related to colour development was identified using the Kyoto encyclopedia of genes and genomes database (KEGG). Subsequently, the expression patterns of 10 candidate differentially expressed genes (DEGs) involved in the flavonoid metabolic pathway were examined, and flavonoids were qualitatively and quantitatively analysed. Numerous anthoxanthins (flavone and flavonol) and a few anthocyanins were detected in the yellow inner-petal, which were all lower than those in the red outer-petal due to the low expression levels of the phenylalanine ammonialyase gene (PlPAL), flavonol synthase gene (PlFLS), dihydroflavonol 4-reductase gene (PlDFR), anthocyanidin synthase gene (PlANS), anthocyanidin 3-O-glucosyltransferase gene (Pl3GT) and anthocyanidin 5-O glucosyltransferase gene (Pl5GT). CONCLUSION: Transcriptome sequencing (RNA-Seq) analysis based on the high throughput sequencing technology was an efficient approach to identify critical genes in P. lactiflora and other non-model plants. The flavonoid metabolic pathway and glucide metabolic pathway were identified as relatived yellow formation in P. lactiflora, PlPAL, PlFLS, PlDFR, PlANS, Pl3GT and Pl5GT were selected as potential candidates involved in flavonoid metabolic pathway, which inducing inhibition of anthocyanin biosynthesis mediated yellow formation in P. lactiflora. This study could lay a theoretical foundation for breeding new yellow P. lactiflora varieties. PMID- 25134526 TI - SCM-198 inhibits microglial overactivation and attenuates Abeta(1-40)-induced cognitive impairments in rats via JNK and NF-kB pathways. AB - BACKGROUND: Neuroinflammation mediated by overactivated microglia plays a key role in many neurodegenerative diseases, including Alzheimer's disease (AD). In this study, we investigated for the first time the anti-neuroinflammatory effects and possible mechanisms of SCM-198 (an alkaloid extracted from Herbaleonuri), which was previously found highly cardioprotective, both in vitro and in vivo. METHODS: For in vitro experiments, lipopolysaccharide (LPS) or beta-amyloid(1-40) (Abeta(1-40)) was applied to induce microglial overactivation. Proinflammatory mediators were measured and activations of NF-kappaB and mitogen-activated protein kinases' (MAPKs) pathways were investigated. Further protective effect of SCM-198 was evaluated in microglia-neuron co-culture assay and Sprague-Dawley (SD) rats intrahippocampally-injected with Abeta(1-40). RESULTS: SCM-198 reduced expressions of nitric oxide (NO), TNF-alpha, IL-1beta and IL-6 possibly via, at least partially, inhibiting c-Jun N-terminal kinase (JNK) and NF-kappaB signaling pathways in microglia. Co-culture assay showed that activated microglia pretreated with SCM-198 led to less neuron loss and decreased phosphorylation of tau and extracellular signal-regulated kinase (ERK) in neurons. Besides, SCM-198 also directly protected against Abeta(1-40)-induced neuronal death and lactate dehydrogenase (LDH) release in primary cortical neurons. For in vivo studies, SCM 198 significantly enhanced cognitive performances of rats 12 days after intrahippocampal injections of aged Abeta(1-40) peptides in the Morris water maze (MWM), accompanied by less hippocampal microglial activation, decreased synaptophysin loss and phosphorylation of ERK and tau. Co-administration of donepezil and SCM-198 resulted in a slight cognitive improvement in SD rats 50 days after intrahippocampal injections of aged Abeta(1-40) peptides as compared to only donepezil or SCM-198 treated group. CONCLUSIONS: Our findings are the first to report that SCM-198 has considerable anti-neuroinflammatory effects on inhibiting microglial overactivation and might become a new potential drug candidate for AD therapy in the future. PMID- 25134528 TI - Radioiodine therapy for thyroid cancer in the era of risk stratification and alternative targeted therapies. AB - Differentiated thyroid cancers are typically iodine-avid and can be effectively treated with radioiodine. In most patients, radioiodine treatment is done for ablation of residual tissue, and in these cases the focus should be on using the minimum effective dose. Adjuvant therapy can be done to reduce the risk of recurrence, but optimal patient selection and dose are unclear. Patients with advanced disease benefit most from treatment with the maximum-tolerated dose. Recent research has focused on better patient selection and reduced radioiodine doses for remnant ablation. There are emerging targeted therapeutic approaches in patients who are appropriately shown to have iodine-refractory disease, with 1 drug approved by the Food and Drug Administration. Numerous trials are ongoing to assess targeted therapeutics alone or in combination with radioiodine. PMID- 25134529 TI - Segmentation-based MR attenuation correction including bones also affects quantitation in brain studies: an initial result of 18F-FP-CIT PET/MR for patients with parkinsonism. AB - Attenuation correction (AC) with an ultrashort echo time (UTE) sequence has recently been used in combination with segmentation for cortical bone identification for brain PET/MR studies. The purpose of this study was to evaluate the quantification of (18)F-fluoropropyl carbomethoxyiodophenylnortropane ((18)F-FP-CIT) binding in brain PET/MR, particularly focusing on effects of UTE-based AC including bone segmentation. METHODS: Sixteen patients with initially suspected parkinsonism were prospectively enrolled. An emission scan was acquired 110 min after (18)F-FP-CIT injection on a dedicated PET/MR scanner, immediately followed by another emission scan using a PET/CT scanner 120 min after the injection. A UTE-based attenuation map was used to classify the voxels into 3 tissues: bone, soft tissue, and air. All PET images were spatially normalized, and a specific-to-nonspecific dopamine transporter (DAT) binding ratio (BR) was calculated using statistical probabilistic anatomic mapping. The level of agreement was assessed with intraclass correlation coefficients (ICCs). Voxelwise comparison between PET images acquired from PET/MR and PET/CT was performed. We compared non-attenuation corrected images to analyze UTE-based AC effects on DAT quantification. RESULTS: BR in the putamen obtained from PET/MR and PET/CT showed low interequipment variability, whereas BR in the caudate nucleus showed significant variability (ICC = 0.967 and 0.682 for putamen and caudate nucleus, respectively). BR in the caudate nucleus was significantly underestimated by PET/MR, compared with PET/CT (mean difference of BR = 0.66, P < 0.0001). Voxelwise analysis revealed that PET/MR showed significantly low BR in the periventricular regions, which was caused by a misclassification of the ventricle as air on the attenuation map. We also compared non-AC images, revealing low interequipment variability even in the caudate nucleus (ICC = 0.937 and 0.832 for putamen and caudate nucleus, respectively). CONCLUSION: Our data demonstrate spatial bias of the DAT BR on (18)F-FP-CIT PET/MR. Voxelwise analysis and comparison to non-AC images identified the misclassification of ventricle as air to be the cause of bias. To obtain reliable quantification for brain PET/MR studies including (18)F-FP-CIT PET, alternative and more reliable segmentation strategies are required. PMID- 25134527 TI - The impact of S6K1 kinase on neuroblastoma cell proliferation is independent of GLI1 signaling. AB - BACKGROUND: The crosstalk between Hedgehog (HH) signaling and other signal transduction cascades has been extensively studied in different cancers. In neuroblastoma, mTOR/S6K1 signaling is known to have a role in the development of this disease and recent evidence also implicates the HH pathway. Moreover, S6K1 kinase has been shown to phosphorylate GLI1, the effector of HH signaling, promoting GLI1 transcriptional activity and oncogenic function in esophageal adenocarcinoma. In this study, we examined the possible interplay of S6K1 and GLI1 signaling in neuroblastoma. METHODS: siRNA knockdowns were used to suppress S6K1 and GLI1 expression, and the siRNA effects were validated by real-time PCR and Western blotting. Cell proliferation analysis was performed with the EdU incorporation assay. Cytotoxic analysis with increasing concentrations of PI3K/mTOR and GLI inhibitors, individually and in combination, was used to determine drug response. RESULTS: Although knockdown of either S6K1 or GLI1 reduces the cellular proliferation of neuroblastoma cells, there is little effect of S6K1 on the expression of GLI1 mRNA and protein and on the capacity of GLI1 to activate target genes. No detectable phosphorylation of GLI1 is observed prior or following S6K1 knockdown. GLI1 overexpression can not rescue the reduced proliferation elicited by S6K1 knockdown. Moreover, inhibitors of PI3K/mTOR and GLI signaling reduced neuroblastoma cell growth, but no additional growth inhibitory effects were detected when the two classes of drugs were combined. CONCLUSION: Our results demonstrate that the impact of S6K1 kinase on neuroblastoma cells is not mediated through modulation of GLI1 expression/activity. PMID- 25134530 TI - Socioeconomic factors and effect of evidence-based patient information about primary prevention of type 2 diabetes mellitus--are there interactions? AB - BACKGROUND: Having shown in a recent randomized controlled trial that evidence based patient information (EBPI) significantly increased knowledge on primary prevention of diabetes compared to standard patient information, we now investigated interaction between socioeconomic status (SES) and the effect of an EBPI. FINDINGS: 1,120 visitors (aged 40-70 years, without known diabetes) to the "Techniker Krankenkasse" and the "German Diabetes Center" websites were randomized. The intervention group received a newly developed on-line EBPI, the control group standard on-line information. The primary outcome measure was knowledge, classified as "good/average/poor". We analyzed associations of knowledge with socioeconomic variables (education, vocational training, employment, subjective social status) combined with intervention effect including interactions, adjusted for possible confounding by knowledge before intervention, self-reported blood glucose measurements, blood pressure, blood lipid levels, age and gender. Logistic regression models were fitted to the subpopulation (n = 647) with complete values in these variables.Education (high vs. low) was significantly associated with knowledge (good vs. average/poor); however, there was no significant interaction between education and intervention. After adjustment, the other socioeconomic variables were not significantly associated with knowledge. CONCLUSIONS: Socioeconomic variables did not significantly change the effect of the intervention. There was a tendency towards a lower effect where lower educated individuals were concerned. Possibly the power was too low to detect interaction effects. Larger studies using SES-specific designs are needed to clarify the effect of SES. We suggest considering the socioeconomic status when evaluating a decision aid, e.g. an EBPI, to ensure its effectiveness not only in higher socioeconomic groups. TRIAL REGISTRATION: Current Controlled Trials ISRCTN22060616 (Date assigned: 12 September 2008). PMID- 25134531 TI - The use of an adjustable electrode housing unit to compare electrode alignment and contact variation with myoelectric prosthesis functionality: A pilot study. AB - BACKGROUND: Usable myoelectric control relies on secure and intimate contact at all times between the electrode, the socket and the residual limb. At present, there is little post-fitting socket adjustment available to prosthetists with respect to electrode contact security or alignment. Failure to provide secure electrode contact could result in the development of motion artefacts, poor prehensor response and subsequent prosthesis non-usage. OBJECTIVES: To establish the effect of alteration to electrode contract security and alignment on prosthesis functionality using a bespoke electrode housing unit. STUDY DESIGN: This study investigated the effect of electrode contact security and alignment on upper limb myoelectric prosthesis functionality. METHODS: Four different electrode housing arrangements were assessed within prosthetic sockets fitted to six transradial prosthesis subjects using the Southampton Hand Assessment Procedure, which is a reliable and validated prosthesis functionality assessment tool. RESULTS: Significantly higher functionality scores were achieved with the bespoke housing unit compared to when using conventional electrode housings. CONCLUSION: Myoelectric prosthesis functionality is closely linked to electrode contact security and to electrode alignment with respect to the residual limb. Both of these factors can be improved locally using an adjustable electrode housing unit. CLINICAL RELEVANCE: Provision of an electrode housing system that enables adjustments to be made to electrode orientation can improve prosthesis functionality, particularly in cases where tight-fitting sockets are not possible, and/or where the prosthetist may be inexperienced with regard to myoelectric prosthesis fitting. PMID- 25134532 TI - Efficacy of a newly designed trunk orthosis with joints providing resistive force in adults with post-stroke hemiparesis. AB - BACKGROUND: Few studies have examined the efficacy of trunk orthoses that support the upper trunk and a paretic limb in stroke patients. To improve stability and alignment of the trunk and pelvis in hemiparetic patients, we developed a newly designed trunk orthosis that provides resistive force through spring joints. OBJECTIVES: This study aimed to determine the newly designed trunk orthosis's biomechanical effects during level walking. STUDY DESIGN: Before-after trials must be better. METHODS: Measurements were taken for nine chronic-phase (>2 years post-onset) stroke patients using a three-dimensional motion capture system and force plates under three experimental conditions: self-selected gait speed without the newly designed trunk orthosis, with the newly designed trunk orthosis, and after newly designed trunk orthosis removal. We analyzed and compared spatiotemporal and kinetic parameters of the paretic and non-paretic limbs and kinematic parameters of the trunk and bilateral limbs. RESULTS: Several pre-swing gait parameters (e.g. hip joint flexion moment and ankle joint plantar flexion angle) after newly designed trunk orthosis removal were significantly increased compared to those without newly designed trunk orthosis. Step length of the paretic limb tended to increase after newly designed trunk orthosis removal. CONCLUSION: The newly designed trunk orthosis effectively modified trunk alignment, but larger improvements in kinetic and kinematic parameters were observed in the bilateral limbs after newly designed trunk orthosis removal than with the newly designed trunk orthosis. CLINICAL RELEVANCE: Stroke patients improved only trunk malalignment while wearing the newly designed trunk orthosis. Gait after newly designed trunk orthosis removal was better than with the newly designed trunk orthosis. Positive changes after removal were mostly observed in pre-swing of the hemiparetic limb. The newly designed trunk orthosis might be effective for gait training in stroke patients. PMID- 25134533 TI - Minimal clinically important difference of the L Test for individuals with lower limb amputation: A pilot study. AB - BACKGROUND: The L Test is a reliable/valid clinical evaluation of mobility that measures walking speed in seconds. It can be used with individuals with lower limb amputation. Responsiveness of the L Test is not yet determined. OBJECTIVES: The purpose of this pilot study was to determine how well the L Test identified individuals with a lower limb amputation who have/have not undergone a minimal clinically important difference. STUDY DESIGN: Prospective follow-up study. METHODS: In total, 33 individuals with lower limb amputation, deemed to require a major intervention, were recruited consecutively from a follow-up clinic. Participants completed the L Test at baseline and follow-up. A Global Rating Change scale was also completed at follow-up. RESULTS: The participants had a mean age +/- standard deviation of 60 +/- 13.0 years, and 81.8% had a transtibial amputation. The mean +/- standard deviation for the L Test change scores was 6.0 +/- 13.9. The area under the curve was 0.67, and the minimal clinically important difference was 4.5 s. CONCLUSIONS: The L Test identified individuals as having an important clinical change. Results must be interpreted with caution, as the accuracy, based on the Global Rating Change scale, is low. Further inquiry into the L Test is encouraged. CLINICAL RELEVANCE: The L Test can guide the clinical management of individuals with lower limb amputation. Results from this pilot study indicate that individuals with a lower limb amputation who improve by at least 4.5 s on the L Test after an intervention have likely undergone an important change. This result must be interpreted with caution given that the ability of the L Test to correctly identify individuals, who have and have not undergone an important change, using the Global Rating Change scale as the gold standard, is limited because this is a pilot study. It is plausible that the precision of the cut-point threshold could increase or decrease given a larger sample or when using a different method of identifying important clinical change. PMID- 25134534 TI - Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women. AB - Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (P(meta)<10(-4)) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, P(meta) = 1.88 * 10(-8)) and 10p11.21 (rs1192691 near ANKRD30A, P(meta) = 2.62 * 10(-8)), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P(meta) = 1.14 * 10(-7)) and 9q34.2 (rs633862 near ABO and SURF6, P(meta) = 8.57 * 10(-7)) (P<0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC. PMID- 25134535 TI - Atomic force microscopy of asymmetric membranes from turtle erythrocytes. AB - The cell membrane provides critical cellular functions that rely on its elaborate structure and organization. The structure of turtle membranes is an important part of an ongoing study of erythrocyte membranes. Using a combination of atomic force microscopy and single-molecule force spectroscopy, we characterized the turtle erythrocyte membrane structure with molecular resolution in a quasi-native state. High-resolution images both leaflets of turtle erythrocyte membranes revealed a smooth outer membrane leaflet and a protein covered inner membrane leaflet. This asymmetry was verified by single-molecule force spectroscopy, which detects numerous exposed amino groups of membrane proteins in the inner membrane leaflet but much fewer in the outer leaflet. The asymmetric membrane structure of turtle erythrocytes is consistent with the semi-mosaic model of human, chicken and fish erythrocyte membrane structure, making the semi-mosaic model more widely applicable. From the perspective of biological evolution, this result may support the universality of the semi-mosaic model. PMID- 25134536 TI - A medium-chain fatty acid, capric acid, inhibits RANKL-induced osteoclast differentiation via the suppression of NF-kappaB signaling and blocks cytoskeletal organization and survival in mature osteoclasts. AB - Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (MCSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow derived macrophages and suppressed RANKL-induced IkappaBalpha phosphorylation, p65 nuclear translocation, and NF-kappaB transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders. PMID- 25134540 TI - Sharp rise in CT scans prompts call for new safeguards on radiation exposure. PMID- 25134538 TI - TAp73 and DeltaNp73 have opposing roles in 5-aza-2'-deoxycytidine-induced apoptosis in breast cancer cells. AB - The p73 gene contains an extrinsic P1 promoter and an intrinsic P2 promoter, controlling the transcription of the pro-apoptotic TAp73 isoform and the anti apoptotic DeltaNup73 isoform, respectively. The DNA methylation status of both promoters act equally in the epigenetic transcriptional regulation of their relevant isoforms. The aim of this study was to analyze the different effects of these p73 isoforms in 5-aza-2'-deoxycytidine (5-aza-dC)-induced apoptosis in breast cancer cells. We investigated the effects of the DNA demethylation agent, 5-aza-dC, on the T-47D breast cancer cell line, and evaluated the methylation status of the p73 promoters and expression of TAp73 and DeltaNp73. Furthermore, we assessed the expression of p53 and p73 isoforms in 5-aza-dC-treated T-47D cells and p53 knockout cells. 5-aza-dC induced significant anti-tumor effects in T-47D cells, including inhibition of cell viability, G1 phase arrest and apoptosis. This was associated with p73 promoter demethylation and a concomitant increase in TAp73 mRNA and protein expression. In contrast, the methylation status of promoter P2 was not associated with DeltaNp73 mRNA or protein levels. Furthermore, demethylation of P2 failed to inhibit the expression of DeltaNp73 with 5-aza-dC in the p53 knockdown cell model. Our study suggests that demethylation of the P1 and P2 promoters has opposite effects on the expression of p73 isoforms, namely up-regulation of TAp73 and down-regulation of DeltaNup73. We also demonstrate that p53 likely contributes to 5-aza-dC-induced DeltaNp73 transcriptional inactivation in breast cancer cells. PMID- 25134537 TI - Oncomodulin/truncated protamine-mediated Nogo-66 receptor small interference RNA delivery promotes axon regeneration in retinal ganglion cells. AB - The optic nerve often suffers regenerative failure after injury, leading to serious visual impairment such as glaucoma. The main inhibitory factors, including Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein, exert their inhibitory effects on axonal growth through the same receptor, the Nogo-66 receptor (NgR). Oncomodulin (OM), a calcium-binding protein with a molecular weight of an ~12 kDa, which is secreted from activated macrophages, has been demonstrated to have high and specific affinity for retinal ganglion cells (RGC) and promote greater axonal regeneration than other known polypeptide growth factors. Protamine has been reported to effectively deliver small interference RNA (siRNA) into cells. Accordingly, a fusion protein of OM and truncated protamine (tp) may be used as a vehicle for the delivery of NgR siRNA into RGC for gene therapy. To test this hypothesis, we constructed OM and tp fusion protein (OM/tp) expression vectors. Using the indirect immunofluorescence labeling method, OM/tp fusion proteins were found to have a high affinity for RGC. The gel shift assay showed that the OM/tp fusion proteins retained the capacity to bind to DNA. Using OM/tp fusion proteins as a delivery tool, the siRNA of NgR was effectively transfected into cells and significantly down-regulated NgR expression levels. More importantly, OM/tp-NgR siRNA dramatically promoted axonal growth of RGC compared with the application of OM/tp recombinant protein or NgR siRNA alone in vitro. In addition, OM/tp-NgR siRNA highly elevated intracellular cyclic adenosine monophosphate (cAMP) levels and inhibited activation of the Ras homolog gene family, member A (RhoA). Taken together, our data demonstrated that the recombinant OM/tp fusion proteins retained the functions of both OM and tp, and that OM/tp-NgR siRNA might potentially be used for the treatment of optic nerve injury. PMID- 25134539 TI - Indacaterol inhibits tumor cell invasiveness and MMP-9 expression by suppressing IKK/NF-kappaB activation. AB - The beta2 adrenergic receptor (ADRB2) is a G protein-coupled transmembrane receptor expressed in the human respiratory tract and widely recognized as a pharmacological target for treatments of asthma and chronic obstructive pulmonary disorder (COPD). Although a number of ADRB2 agonists have been developed for use in asthma therapy, indacaterol is the only ultra-long-acting inhaled beta2 agonist (LABA) approved by the FDA for relieving the symptoms in COPD patients. The precise molecular mechanism underlying the pharmacological effect of indacaterol, however, remains unclear. Here, we show that beta-arrestin-2 mediates the internalization of ADRB2 following indacaterol treatment. Moreover, we demonstrate that indacaterol significantly inhibits tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activity by reducing levels of both phosphorylated-IKK and -IkappaBalpha, thereby decreasing NF-kappaB nuclear translocation and the expression of MMP-9, an NF-kappaB target gene. Subsequently, we show that indacaterol significantly inhibits TNF-alpha/NF-kappaB induced cell invasiveness and migration in a human cancer cell line. In conclusion, we propose that indacaterol may inhibit NF-kappaB activity in a beta arrestin2-dependent manner, preventing further lung damage and improving lung function in COPD patients. PMID- 25134541 TI - Oral susceptibility of Aedes aegypti (Diptera: Culicidae) from Senegal for dengue serotypes 1 and 3 viruses. AB - OBJECTIVE: To investigate the potential for domestic and wild populations of Aedes aegypti from Dakar and Kedougou to develop a disseminated infection after exposure to DENV-3 and DENV-1. METHODS: We have exposed sylvatic and urban population of Ae. aegypti from Senegal to bloomeals containing dengue serotype 1 and 3. At different incubation period, individual mosquito legs/wings and bodies were tested for virus presence using real time RT-PCR to estimate the infection and dissemination rates. RESULTS: The data indicated low susceptibility to DENV-3 (infection: 2.4-15.2%, and dissemination rates: 0-8.3%) and higher susceptibility to DENV-1 (infection and dissemination rates up to 50%). CONCLUSION: Aedes aegypti from Senegal seem able to develop a disseminated infection of DENV-1 and DENV-3. Further studies are needed to test their ability to transmit the two serotypes. PMID- 25134543 TI - Communication: The distinguishable cluster approximation. II. The role of orbital relaxation. AB - The distinguishable cluster approximation proposed in Paper I [D. Kats and F. R. Manby, J. Chem. Phys. 139, 021102 (2013)] has shown intriguing abilities to accurately describe potential energy surfaces in various notoriously difficult cases. The question that still remained open is to what extend the accuracy and the stability of the method is due to the special choice of orbital-relaxation treatment. In this paper we introduce orbital relaxation in terms of Brueckner orbitals, orbital optimization, and projective singles into the distinguishable cluster approximation and investigate its importance in single- and multireference cases. All three resulting methods are able to cope with many multiple-bond breaking problems, but in some difficult cases where the Hartree Fock orbitals seem to be entirely inadequate the orbital-optimized version turns out to be superior. PMID- 25134544 TI - Communication: Escape kinetics of self-propelled Janus particles from a cavity: numerical simulations. AB - We numerically investigate the escape kinetics of elliptic Janus particles from narrow two-dimensional cavities with reflecting walls. The self-propulsion velocity of the Janus particle is directed along either their major (prolate) or minor (oblate) axis. We show that the mean exit time is very sensitive to the cavity geometry, particle shape, and self-propulsion strength. The mean exit time is found to be a minimum when the self-propulsion length is equal to the cavity size. We also find the optimum mean escape time as a function of the self propulsion velocity, translational diffusion, and particle shape. Thus, effective transport control mechanisms for Janus particles in a channel can be implemented. PMID- 25134542 TI - Cellular dosimetry calculations for Strontium-90 using Monte Carlo code PENELOPE. AB - PURPOSE: To improve risk assessments associated with chronic exposure to Strontium-90 (Sr-90), for both the environment and human health, it is necessary to know the energy distribution in specific cells or tissue. Monte Carlo (MC) simulation codes are extremely useful tools for calculating deposition energy. The present work was focused on the validation of the MC code PENetration and Energy LOss of Positrons and Electrons (PENELOPE) and the assessment of dose distribution to bone marrow cells from punctual Sr-90 source localized within the cortical bone part. MATERIALS AND METHODS: S-values (absorbed dose per unit cumulated activity) calculations using Monte Carlo simulations were performed by using PENELOPE and Monte Carlo N-Particle eXtended (MCNPX). Cytoplasm, nucleus, cell surface, mouse femur bone and Sr-90 radiation source were simulated. Cells are assumed to be spherical with the radii of the cell and cell nucleus ranging from 2-10 MUm. The Sr-90 source is assumed to be uniformly distributed in cell nucleus, cytoplasm and cell surface. RESULTS: The comparison of S-values calculated with PENELOPE to MCNPX results and the Medical Internal Radiation Dose (MIRD) values agreed very well since the relative deviations were less than 4.5%. The dose distribution to mouse bone marrow cells showed that the cells localized near the cortical part received the maximum dose. CONCLUSION: The MC code PENELOPE may prove useful for cellular dosimetry involving radiation transport through materials other than water, or for complex distributions of radionuclides and geometries. PMID- 25134546 TI - A renormalized potential-following propagation algorithm for solving the coupled channels equations. AB - We derive a general renormalized potential-following propagation method that efficiently solves the coupled-channels equations. The step size is variable, the method is compatible with reactive boundary conditions, and the algorithm may be combined with other renormalized algorithms, such as renormalized Numerov. We diagonalize the coupling matrix and consider piece-wise constant and linear reference potentials. The constant reference potential algorithm is very simple to implement, yet for multichannel problems almost as accurate as the linear reference potential method. The applicability of the proposed algorithms to realistic problems is demonstrated for cold collisions of NH radicals. The renormalized approach has the advantage of producing wave functions in a straightforward way, which is illustrated for a shape resonance in NH-NH collisions. These scattering wave functions can be used to study ultracold photoassociation and near-threshold photodissociation. PMID- 25134545 TI - Multiple branched adaptive steered molecular dynamics. AB - Steered molecular dynamics, SMD, [S. Park and K. Schulten, J. Chem. Phys. 120, 5946 (2004)] combined with Jarzynski's equality has been used widely in generating free energy profiles for various biological problems, e.g., protein folding and ligand binding. However, the calculated averages are generally dominated by "rare events" from the ensemble of nonequilibrium trajectories. The recently proposed adaptive steered molecular dynamics, ASMD, introduced a new idea for selecting important events and eliminating the non-contributing trajectories, thus decreasing the overall computation needed. ASMD was shown to reduce the number of trajectories needed by a factor of 10 in a benchmarking study of decaalanine stretching. Here we propose a novel, highly efficient "multiple branching" (MB) version, MB-ASMD, which obtains a more complete enhanced sampling of the important trajectories, while still eliminating non contributing segments. Compared to selecting a single configuration in ASMD, MB ASMD offers to select multiple configurations at each segment along the reaction coordinate based on the distribution of work trajectories. We show that MB-ASMD has all benefits of ASMD such as faster convergence of the PMF even when pulling 1000 times faster than the reversible limit while greatly reducing the probability of getting trapped in a non-significant path. We also analyze the hydrogen bond breaking within the decaalanine peptide as we force the helix into a random coil and confirm ASMD results with less noise in the numerical averages. PMID- 25134547 TI - Fundamental measure theory for smectic phases: scaling behavior and higher order terms. AB - The recent extension of Rosenfeld's fundamental measure theory to anisotropic hard particles predicts nematic order of rod-like particles. Our analytic study of different aligned shapes provides new insights into the structure of this density functional, which is basically founded on experience with hard spheres. We combine scaling arguments with dimensional crossover and motivate a modified expression, which enables an appropriate description of smectic layering. We calculate the nematic-smectic-A transition of monodisperse hard spherocylinders with and without orientational degrees of freedom and present the equation of state and phase diagram including these two liquid crystalline phases in good agreement with simulations. We also find improved results related to the isotropic-nematic interface. We discuss the quality of empirical corrections and the convergence towards an exact second virial coefficient, including higher order terms. PMID- 25134548 TI - Analytic derivative couplings for spin-flip configuration interaction singles and spin-flip time-dependent density functional theory. AB - We revisit the calculation of analytic derivative couplings for configuration interaction singles (CIS), and derive and implement these couplings for its spin flip variant for the first time. Our algorithm is closely related to the CIS analytic energy gradient algorithm and should be straightforward to implement in any quantum chemistry code that has CIS analytic energy gradients. The additional cost of evaluating the derivative couplings is small in comparison to the cost of evaluating the gradients for the two electronic states in question. Incorporation of an exchange-correlation term provides an ad hoc extension of this formalism to time-dependent density functional theory within the Tamm-Dancoff approximation, without the need to invoke quadratic response theory or evaluate third derivatives of the exchange-correlation functional. Application to several different conical intersections in ethylene demonstrates that minimum-energy crossing points along conical seams can be located at substantially reduced cost when analytic derivative couplings are employed, as compared to use of a branching-plane updating algorithm that does not require these couplings. Application to H3 near its D(3h) geometry demonstrates that correct topology is obtained in the vicinity of a conical intersection involving a degenerate ground state. PMID- 25134549 TI - The multifacet graphically contracted function method. I. Formulation and implementation. AB - The basic formulation for the multifacet generalization of the graphically contracted function (MFGCF) electronic structure method is presented. The analysis includes the discussion of linear dependency and redundancy of the arc factor parameters, the computation of reduced density matrices, Hamiltonian matrix construction, spin-density matrix construction, the computation of optimization gradients for single-state and state-averaged calculations, graphical wave function analysis, and the efficient computation of configuration state function and Slater determinant expansion coefficients. Timings are given for Hamiltonian matrix element and analytic optimization gradient computations for a range of model problems for full-CI Shavitt graphs, and it is observed that both the energy and the gradient computation scale as O(N(2)n(4)) for N electrons and n orbitals. The important arithmetic operations are within dense matrix matrix product computational kernels, resulting in a computationally efficient procedure. An initial implementation of the method is used to present applications to several challenging chemical systems, including N2 dissociation, cubic H8 dissociation, the symmetric dissociation of H2O, and the insertion of Be into H2. The results are compared to the exact full-CI values and also to those of the previous single-facet GCF expansion form. PMID- 25134550 TI - The multifacet graphically contracted function method. II. A general procedure for the parameterization of orthogonal matrices and its application to arc factors. AB - Practical algorithms are presented for the parameterization of orthogonal matrices Q ? R(m*n) in terms of the minimal number of essential parameters {phi}. Both square n = m and rectangular n < m situations are examined. Two separate kinds of parameterizations are considered, one in which the individual columns of Q are distinct, and the other in which only Span(Q) is significant. The latter is relevant to chemical applications such as the representation of the arc factors in the multifacet graphically contracted function method and the representation of orbital coefficients in SCF and DFT methods. The parameterizations are represented formally using products of elementary Householder reflector matrices. Standard mathematical libraries, such as LAPACK, may be used to perform the basic low-level factorization, reduction, and other algebraic operations. Some care must be taken with the choice of phase factors in order to ensure stability and continuity. The transformation of gradient arrays between the Q and {phi} parameterizations is also considered. Operation counts for all factorizations and transformations are determined. Numerical results are presented which demonstrate the robustness, stability, and accuracy of these algorithms. PMID- 25134551 TI - Mesodynamics with implicit degrees of freedom. AB - Mesoscale phenomena--involving a level of description between the finest atomistic scale and the macroscopic continuum--can be studied by a variation on the usual atomistic-level molecular dynamics (MD) simulation technique. In mesodynamics, the mass points, rather than being atoms, are mesoscopic in size, for instance, representing the centers of mass of polycrystalline grains or molecules. In order to reproduce many of the overall features of fully atomistic MD, which is inherently more expensive, the equations of motion in mesodynamics must be derivable from an interaction potential that is faithful to the compressive equation of state, as well as to tensile de-cohesion that occurs along the boundaries of the mesoscale units. Moreover, mesodynamics differs from Newton's equations of motion in that dissipation--the exchange of energy between mesoparticles and their internal degrees of freedom (DoFs)--must be described, and so should the transfer of energy between the internal modes of neighboring mesoparticles. We present a formulation where energy transfer between the internal modes of a mesoparticle and its external center-of-mass DoFs occurs in the phase space of mesoparticle coordinates, rather than momenta, resulting in a Galilean invariant formulation that conserves total linear momentum and energy (including the energy internal to the mesoparticles). We show that this approach can be used to describe, in addition to mesoscale problems, conduction electrons in atomic-level simulations of metals, and we demonstrate applications of mesodynamics to shockwave propagation and thermal transport. PMID- 25134552 TI - Sampling microcanonical ensembles of trajectories using harmonic approximation in internal coordinates. AB - In this paper, we modify quasiclassical harmonic sampling of microcanonical ensembles of trajectories by using the curvilinear internal coordinates. The harmonic approximation in the curvilinear normal coordinates provides a more realistic description of the PES than in the conventional rectilinear ones at finite displacements. Therefore, the sampling of vibrations in the internal coordinates significantly improves the quality of the sampling in a block-box fashion, providing more realistic displacements and reducing the errors in the potential energy. In particular, the sampling of large-amplitude torsion vibrations, which is non-realistic in the Cartesian modes, becomes accurate or acceptable in the curvilinear modes. PMID- 25134553 TI - Nematic-smectic transition of parallel hard spheroellipsoids. AB - Spheroellipsoids are truncated ellipsoids with spherical end caps. If gradients are assumed to change smoothly at the junction of body and cap, the truncation height z0 determines the geometry uniquely. The resulting model particle has only two shape parameters, namely, the aspect ratio c/a of the basic ellipsoid and the cutoff z0/a. These two parameters can be tuned to yield a continuous transformation between a pure ellipsoid and a spherocylinder. Since parallel hard spherocylinders display a nematic-smectic A phase transition, while ellipsoids do not, the influence of the particle shape on the possibility of a smectic phase may be investigated. A density functional analysis is used to detect the dividing line, in the (c/a, z0/a) plane, between the presence and absence of the N-S transition. Since spheroellipsoids may be useful as generic model particles for anisotropic molecules, we provide a computationally efficient overlap criterion for a pair in a general, non-parallel configuration. PMID- 25134554 TI - Finite-density effects in the Fredrickson-Andersen and Kob-Andersen kinetically constrained models. AB - We calculate the corrections to the thermodynamic limit of the critical density for jamming in the Kob-Andersen and Fredrickson-Andersen kinetically-constrained models, and find them to be finite-density corrections, and not finite-size corrections. We do this by introducing a new numerical algorithm, which requires negligible computer memory since contrary to alternative approaches, it generates at each point only the necessary data. The algorithm starts from a single unfrozen site and at each step randomly generates the neighbors of the unfrozen region and checks whether they are frozen or not. Our results correspond to systems of size greater than 10(7) * 10(7), much larger than any simulated before, and are consistent with the rigorous bounds on the asymptotic corrections. We also find that the average number of sites that seed a critical droplet is greater than 1. PMID- 25134555 TI - Theory of charge transport in molecular junctions: from Coulomb blockade to coherent tunneling. AB - We study charge transport through molecular junctions in the presence of electron electron interaction using the nonequilibrium Green's function techniques and the renormalized perturbation theory. In the perturbation treatment, the zeroth-order Hamiltonian of the molecular junction is composed of independent single-impurity Anderson's models, which act as the channels where charges come through or occupy, and the interactions between different channels are treated as the perturbation. Using this scheme, the effects of molecule-lead, electron-electron, and hopping interactions are included nonperturbatively, and the charge transport processes can thus be studied in the intermediate parameter range from the Coulomb blockade to the coherent tunneling regimes. The concept of quasi particles is introduced to describe the kinetic process of charge transport, and then the electric current can be studied and calculated. As a test study, the Hubbard model is used as the molecular Hamiltonian to simulate dimeric and trimeric molecular junctions. Various nonlinear current-voltage characteristics, including Coulomb blockade, negative differential resistance, rectification, and current hysteresis, are shown in the calculations, and the mechanisms are elucidated. PMID- 25134556 TI - Computation of the memory functions in the generalized Langevin models for collective dynamics of macromolecules. AB - We present a numerical method to approximate the memory functions in the generalized Langevin models for the collective dynamics of macromolecules. We first derive the exact expressions of the memory functions, obtained from projection to subspaces that correspond to the selection of coarse-grain variables. In particular, the memory functions are expressed in the forms of matrix functions, which will then be approximated by Krylov-subspace methods. It will also be demonstrated that the random noise can be approximated under the same framework, and the second fluctuation-dissipation theorem is automatically satisfied. The accuracy of the method is examined through several numerical examples. PMID- 25134557 TI - The third-order algebraic diagrammatic construction method (ADC(3)) for the polarization propagator for closed-shell molecules: efficient implementation and benchmarking. AB - The implementation of an efficient program of the algebraic diagrammatic construction method for the polarisation propagator in third-order perturbation theory (ADC(3)) for the computation of excited states is reported. The accuracies of ADC(2) and ADC(3) schemes have been investigated with respect to Thiel's recently established benchmark set for excitation energies and oscillator strengths. The calculation of 141 vertical excited singlet and 71 triplet states of 28 small to medium-sized organic molecules has revealed that ADC(3) exhibits mean error and standard deviation of 0.12 +/- 0.28 eV for singlet states and 0.18 +/- 0.16 eV for triplet states when the provided theoretical best estimates are used as benchmark. Accordingly, the ADC(2)-s and ADC(2)-x calculations revealed accuracies of 0.22 +/- 0.38 eV and -0.70 +/- 0.37 eV for singlets and 0.12 +/- 0.16 eV and -0.55 +/- 0.20 eV for triplets, respectively. For a comparison of CC3 and ADC(3), only non-CC3 benchmark values were considered, which comprise 84 singlet states and 19 triplet states. For these singlet states CC3 exhibits an accuracy of 0.23 +/- 0.21 eV and ADC(3) an accuracy of 0.08 +/- 0.27 eV, and accordingly for the triplet states of 0.12 +/- 0.10 eV and -0.10 +/- 0.13 eV, respectively. Hence, based on the quality of the existing benchmark set it is practically not possible to judge whether ADC(3) or CC3 is more accurate, however, ADC(3) has a much larger range of applicability due to its more favourable scaling of O(N(6)) with system size. PMID- 25134559 TI - An improved classical mapping method for homogeneous electron gases at finite temperature. AB - We introduce a modified classical mapping method to predict the exchange correlation free energy and the structure of homogeneous electron gases (HEG) at finite temperature. With the classical map temperature parameterized on the basis of the quantum Monte Carlo simulation data for the correlation energy and exact results at high and low temperature limits, the new theoretical procedure greatly improves the classical mapping method for correlating the energetic properties HEG over a broad range of thermodynamic conditions. Improvement can also be identified in predicting the long-range components of the spin-averaged pair correlation functions. PMID- 25134558 TI - Testing procedures for extracting fluctuation spectra from lipid bilayer simulations. AB - To address concerns about how to obtain the height-height spectrum from simulations of biomembranes, we emulated the fluctuations in real space using exact input spectra. Two different methods that have given different results in the literature were then used to extract spectra from the emulated fluctuations that were then compared to the exact input spectra. A real space method shows systematic, but small deviations attributed to splines introducing an artifactual filter. A direct Fourier method obtains accurate results when the in-plane placement of the emulated particles is uncorrelated with the out-of-plane undulations, but systematic underestimates occur when the particle placement is more realistically correlated with the undulations. Although quantitative corrections cannot be estimated from our one-dimensional model, the results are qualitatively consistent with the direct Fourier method underestimating the 1/q(2) spectral dependence that is characteristic of a tilt degree of freedom in simulations. PMID- 25134560 TI - Free energy of RNA-counterion interactions in a tight-binding model computed by a discrete space mapping. AB - The thermodynamic stability of a folded RNA is intricately tied to the counterions and the free energy of this interaction must be accounted for in any realistic RNA simulations. Extending a tight-binding model published previously, in this paper we investigate the fundamental structure of charges arising from the interaction between small functional RNA molecules and divalent ions such as Mg(2+) that are especially conducive to stabilizing folded conformations. The characteristic nature of these charges is utilized to construct a discretely connected energy landscape that is then traversed via a novel application of a deterministic graph search technique. This search method can be incorporated into larger simulations of small RNA molecules and provides a fast and accurate way to calculate the free energy arising from the interactions between an RNA and divalent counterions. The utility of this algorithm is demonstrated within a fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena group I intron, in which it is shown that the counterion-mediated free energy conclusively directs folding into a compact structure. PMID- 25134561 TI - Universal scaling of potential energy functions describing intermolecular interactions. I. Foundations and scalable forms of new generalized Mie, Lennard Jones, Morse, and Buckingham exponential-6 potentials. AB - Based on the formulation of the analytical expression of the potential V(r) describing intermolecular interactions in terms of the dimensionless variables r* = r/r(m) and E* = V/E, where r(m) is the separation at the minimum and E the well depth, we propose more generalized scalable forms for the commonly used Mie, Lennard-Jones, Morse, and Buckingham exponential-6 potential energy functions. These new generalized forms have an additional parameter from the original forms and revert to the original ones for some choice of that parameter. In this respect, the original forms of those potentials can be considered as special cases of the more general forms that are introduced. We also propose a scalable, non-revertible to the original one, 4-parameter extended Morse potential. PMID- 25134562 TI - Universal scaling of potential energy functions describing intermolecular interactions. II. The halide-water and alkali metal-water interactions. AB - The scaled versions of the newly introduced [S. S. Xantheas and J. C. Werhahn, J. Chem. Phys. 141, 064117 (2014)] generalized forms of some popular potential energy functions (PEFs) describing intermolecular interactions--Mie, Lennard Jones, Morse, and Buckingham exponential-6--have been used to fit the ab initio relaxed approach paths and fixed approach paths for the halide-water, X(-)(H2O), X = F, Cl, Br, I, and alkali metal-water, M(+)(H2O), M = Li, Na, K, Rb, Cs, interactions. The generalized forms of those PEFs have an additional parameter with respect to the original forms and produce fits to the ab initio data that are between one and two orders of magnitude better in the chi(2) than the original PEFs. They were found to describe both the long-range, minimum and repulsive wall of the respective potential energy surfaces quite accurately. Overall the 4-parameter extended Morse (eM) and generalized Buckingham exponential-6 (gBe-6) potentials were found to best fit the ab initio data for these two classes of ion-water interactions. The fitted values of the parameter of the (eM) and (gBe-6) PEFs that control the repulsive wall of the potential correlate remarkably well with the ionic radii of the halide and alkali metal ions. PMID- 25134563 TI - Comparison of double-quantum NMR normalization schemes to measure homonuclear dipole-dipole interactions. AB - A recent implementation of a double-quantum (DQ) recoupling solid-state NMR experiment, dubbed DQ-DRENAR, provides a quantitative measure of homonuclear dipole-dipole coupling constants in multispin-1/2 systems. It was claimed to be more robust than another, previously known experiment relying on the recording of point-by-point normalized DQ build-up curves. Focusing on the POST-C7 and BaBa xy16 DQ pulse sequences, I here present an in-depth comparison of both approaches based upon spin-dynamics simulations, stressing that they are based upon very similar principles and that they are largely equivalent when no imperfections are present. With imperfections, it is found that DQ-DRENAR/POST-C7 does not fully compensate for additional signal dephasing related to chemical shifts (CS) and their anisotropy (CSA), which over-compensates the intrinsic CS(A)-related efficiency loss of the DQ Hamiltonian and leads to an apparent cancellation effect. The simulations further show that the CS(A)-related dephasing in DQ DRENAR can be removed by another phase cycle step or an improved super-cycled wideband version. Only the latter, or the normalized DQ build-up, are unaffected by CS(A)-related signal loss and yield clean pure dipolar-coupling information subject to unavoidable, pulse sequence specific performance reduction related to higher-order corrections of the dipolar DQ Hamiltonian. The intrinsically super cycled BaBa-xy16 is shown to exhibit virtually no CS(A) related imperfection terms, but its dipolar performance is somewhat more challenged by CS(A) effects than POST-C7, which can however be compensated when applied at very fast MAS (>50 kHz). Practically, DQ-DRENAR uses a clever phase cycle separation to achieve a significantly shorter experimental time, which can also be beneficially employed in normalized DQ build-up experiments. PMID- 25134565 TI - Hydrogen migration in formation of NH(A3Pi) radicals via superexcited states in photodissociation of isoxazole molecules. AB - Formation of the excited NH(A(3)Pi) free radicals in the photodissociation of isoxazole (C3H3NO) molecules has been studied over the 14-22 eV energy range using photon-induced fluorescence spectroscopy. The NH(A(3)Pi) is produced through excitation of the isoxazole molecules into higher-lying superexcited states. Observation of the NH radical, which is not a structural unit of the isoxazole molecule, corroborates the hydrogen atom (or proton) migration within the molecule prior to dissociation. The vertical excitation energies of the superexcited states were determined and the dissociation mechanisms of isoxazole are discussed. The density functional and ab initio quantum chemical calculations have been performed to study the mechanism of the NH formation. PMID- 25134566 TI - Dissociation of H2 on carbon doped aluminum cluster Al6C. AB - The dissociation of H2 molecule is the first step for chemical storage of hydrogen, and the energy barrier of the dissociation is the key factor to decide the kinetics of the regeneration of the storage material. As a light element, aluminum is an important candidate component for storage materials with high gravimetric density. This paper investigates the adsorption and dissociation of H2 on carbon doping aluminum cluster Al6C. The study shows that doping carbon into aluminum cluster can significantly change the electronic structure and increase the stability. Al6C has a few stable isomers with close energies and their structures are quite flexible. The molecular adsorption of H2 on Al6C is very weak, but the H2 molecule can be dissociated easily on this cluster. The stable product of the dissociated adsorption is searched and the different paths for the dissociation are investigated. During the dissociation of H2, the structure of the cluster adjusts accordingly, and strong orbital interaction between the hydrogen and the cluster occurs. The calculated energy barrier for the dissociation is only 0.30 eV, which means the dissociation can take place at moderate temperatures. PMID- 25134564 TI - Overhauser effects in insulating solids. AB - We report magic angle spinning, dynamic nuclear polarization (DNP) experiments at magnetic fields of 9.4 T, 14.1 T, and 18.8 T using the narrow line polarizing agents 1,3-bisdiphenylene-2-phenylallyl (BDPA) dispersed in polystyrene, and sulfonated-BDPA (SA-BDPA) and trityl OX063 in glassy glycerol/water matrices. The (1)H DNP enhancement field profiles of the BDPA radicals exhibit a significant DNP Overhauser effect (OE) as well as a solid effect (SE) despite the fact that these samples are insulating solids. In contrast, trityl exhibits only a SE enhancement. Data suggest that the appearance of the OE is due to rather strong electron-nuclear hyperfine couplings present in BDPA and SA-BDPA, which are absent in trityl and perdeuterated BDPA (d21-BDPA). In addition, and in contrast to other DNP mechanisms such as the solid effect or cross effect, the experimental data suggest that the OE in non-conducting solids scales favorably with magnetic field, increasing in magnitude in going from 5 T, to 9.4 T, to 14.1 T, and to 18.8 T. Simulations using a model two spin system consisting of an electron hyperfine coupled to a (1)H reproduce the essential features of the field profiles and indicate that the OE in these samples originates from the zero and double quantum cross relaxation induced by fluctuating hyperfine interactions between the intramolecular delocalized unpaired electrons and their neighboring nuclei, and that the size of these hyperfine couplings is crucial to the magnitude of the enhancements. Microwave power dependent studies show that the OE saturates at considerably lower power levels than the solid effect in the same samples. Our results provide new insights into the mechanism of the Overhauser effect, and also provide a new approach to perform DNP experiments in chemical, biophysical, and physical systems at high magnetic fields. PMID- 25134567 TI - Ab initio potential energy surface for methane and carbon dioxide and application to vapor-liquid coexistence. AB - A six-dimensional intermolecular potential energy surface for a rigid methane (CH4) and carbon dioxide (CO2) dimer was developed from the counterpoise corrected supermolecular approach at the CCSD(T) level of theory. A total of 466 grid points distributed to 46 orientations were calculated from the complete basis set limit extrapolation based on up to aug-cc-pVQZ basis set. A modified site-site pair potential function was proposed for rapid representation of the high level ab initio calculations. A nonadditive three-body interaction was represented by the Axilrod-Teller-Muto expression for mixtures with the polarizability and the London dispersion constant of each molecule. Second to fourth virial coefficients of CH4 and CO2 mixtures were calculated using both the Mayer sampling Monte Carlo method and the present potential functions. The virial equation of state derived from these coefficients was used to predict the pVT values and showed good agreement with experimental data below 200 bar at 300 K. The vapor-liquid coexistence curves of pure CH4, CO2 and their mixtures were presented with the aid of Gibbs ensemble Monte Carlo simulations. The predicted tie lines agreed with the experimental data within the uncertainties up to near the critical point. PMID- 25134568 TI - Rotational analysis of the 301 band of the A6Sigma+ <- X6Sigma+ system of CrCCH. AB - The spectrum of chromium acetylide, CrCCH, has been investigated in the near infrared region (10,500-14,500 cm(-1)) and an intense band system is observed. The 301 band of this system has been investigated at high resolution (0.025 cm( 1)) and this system is identified as the A6Sigma+ <- X6Sigma+ system, analogous to the near IR spectra of the CrH, CrF, and CrCl molecules. Among the many unidentified lines, we have assigned 341 lines belonging to 43 of the 54 allowed branches. Using combination differences, the rotational constants of the ground state have been determined. Computational results on the ground state are also reported, along with a comparison to other monoligated monovalent chromium compounds. PMID- 25134569 TI - Resonances in photoabsorption: predissociation line shapes in the 3ppiD1Pi(u)+ <- X1Sigma(g)+ system in H2. AB - The predissociation of the 3ppiD1Pi(u)+, v >= 3, N = 2, and N = 3 levels of diatomic hydrogen is calculated by ab initio multichannel quantum defect theory combined with a R-matrix type approach that accounts for interfering predissociation and autoionization. The theory yields absorption line widths and shapes that are in good agreement with those observed in the high-resolution synchrotron vacuum-ultraviolet absorption spectra obtained by Dickenson et al. [J. Chem. Phys. 133, 144317 (2010)] at the DESIRS beamline of the SOLEIL synchrotron. The theory predicts further that many of the D state resonances with v ? 6 exhibit a complex fine structure which cannot be modeled by the Fano profile formula and which has not yet been observed experimentally. PMID- 25134570 TI - A comparative account of quantum dynamics of the H+ + H2 reaction at low temperature on two different potential energy surfaces. AB - Rotationally resolved reaction probabilities, integral cross sections, and rate constant for the H(+) + H2 (v = 0, j = 0 or 1) -> H2 (v' = 0, j') + H(+) reaction are calculated using a time-independent quantum mechanical method and the potential energy surface of Kamisaka et al. [J. Chem. Phys. 116, 654 (2002)] (say KBNN PES). All partial wave contributions of the total angular momentum, J, are included to obtain converged cross sections at low collision energies and rate constants at low temperatures. In order to test the accuracy of the KBNN PES, the results obtained here are compared with those obtained in our earlier work [P. Honvault et al., Phys. Rev. Lett. 107, 023201 (2011)] using the accurate potential energy surface of Velilla et al. [J. Chem. Phys. 129, 084307 (2008)]. Integral cross sections and rate constants obtained on the two potential energy surfaces considered here show remarkable differences in terms of magnitude and dependence on collision energy (or temperature) which can be attributed to the differences observed in the topography of the surfaces near to the entrance channel. This clearly shows the inadequacy of the KBNN PES for calculations at low collision energies. PMID- 25134571 TI - Interatomic Coulombic decay following resonant core excitation of Ar in argon dimer. AB - A scheme utilizing excitation of core electrons followed by the resonant-Auger - interatomic Coulombic decay (RA-ICD) cascade was recently proposed as a means of controlling the generation site and energies of slow ICD electrons. This control mechanism was verified in a series of experiments in rare gas dimers. In this article, we present fully ab initio computed ICD electron and kinetic energy release spectra produced following 2p(3/2) -> 4s, 2p(1/2) -> 4s, and 2p(3/2) -> 3d core excitations of Ar in Ar2. We demonstrate that the manifold of ICD states populated in the resonant Auger process comprises two groups. One consists of lower energy ionization satellites characterized by fast interatomic decay, while the other consists of slow decaying higher energy ionization satellites. We show that accurate description of nuclear dynamics in the latter ICD states is crucial for obtaining theoretical electron and kinetic energy release spectra in good agreement with the experiment. PMID- 25134572 TI - Electronic and optical properties of pure and modified diamondoids studied by many-body perturbation theory and time-dependent density functional theory. AB - Diamondoids are small diamond nanoparticles (NPs) that are built up from diamond cages. Unlike usual semiconductor NPs, their atomic structure is exactly known, thus they are ideal test-beds for benchmarking quantum chemical calculations. Their usage in spintronics and bioimaging applications requires a detailed knowledge of their electronic structure and optical properties. In this paper, we apply density functional theory (DFT) based methods to understand the electronic and optical properties of a few selected pure and modified diamondoids for which accurate experimental data exist. In particular, we use many-body perturbation theory methods, in the G0W0 and G0W0+BSE approximations, and time-dependent DFT in the adiabatic local density approximation. We find large quasiparticle gap corrections that can exceed thrice the DFT gap. The electron-hole binding energy can be as large as 4 eV but it is considerably smaller than the GW corrections and thus G0W0+BSE optical gaps are about 50% larger than the Kohn-Sham (KS) DFT gaps. We find significant differences between KS time-dependent DFT and GW+BSE optical spectra on the selected diamondoids. The calculated G0W0 quasiparticle levels agree well with the corresponding experimental vertical ionization energies. We show that nuclei dynamics in the ionization process can be significant and its contribution may reach about 0.5 eV in the adiabatic ionization energies. PMID- 25134573 TI - Brownian aggregation rate of colloid particles with several active sites. AB - We theoretically analyze the aggregation kinetics of colloid particles with several active sites. Such particles (so-called "patchy particles") are well known as chemically anisotropic reactants, but the corresponding rate constant of their aggregation has not yet been established in a convenient analytical form. Using kinematic approximation for the diffusion problem, we derived an analytical formula for the diffusion-controlled reaction rate constant between two colloid particles (or clusters) with several small active sites under the following assumptions: the relative translational motion is Brownian diffusion, and the isotropic stochastic reorientation of each particle is Markovian and arbitrarily correlated. This formula was shown to produce accurate results in comparison with more sophisticated approaches. Also, to account for the case of a low number of active sites per particle we used Monte Carlo stochastic algorithm based on Gillespie method. Simulations showed that such discrete model is required when this number is less than 10. Finally, we applied the developed approach to the simulation of immunoagglutination, assuming that the formed clusters have fractal structure. PMID- 25134574 TI - Spectroscopy and picosecond dynamics of aqueous NO2. AB - We investigate the formation of aqueous nitrogen dioxide, NO2 formed through femtosecond photolysis of nitrate, NO3- and nitromethane CH3NO2(aq). Common to the experiments is the observation of a strong induced absorption at 1610 +/- 10 cm(-1), assigned to the asymmetric stretch vibration in the ground state of NO2. This assignment is substantiated through isotope experiments substituting (14)N by (15)N, experiments at different pH values, and by theoretical calculations and simulations of NO2-D2O clusters. PMID- 25134575 TI - The non-statistical dynamics of the 18O + 32O2 isotope exchange reaction at two energies. AB - The dynamics of the (18)O((3)P) + (32)O2 isotope exchange reaction were studied using crossed atomic and molecular beams at collision energies (E(coll)) of 5.7 and 7.3 kcal/mol, and experimental results were compared with quantum statistical (QS) and quasi-classical trajectory (QCT) calculations on the O3(X(1)A') potential energy surface (PES) of Babikov et al. [D. Babikov, B. K. Kendrick, R. B. Walker, R. T. Pack, P. Fleurat-Lesard, and R. Schinke, J. Chem. Phys. 118, 6298 (2003)]. In both QS and QCT calculations, agreement with experiment was markedly improved by performing calculations with the experimental distribution of collision energies instead of fixed at the average collision energy. At both collision energies, the scattering displayed a forward bias, with a smaller bias at the lower E(coll). Comparisons with the QS calculations suggest that (34)O2 is produced with a non-statistical rovibrational distribution that is hotter than predicted, and the discrepancy is larger at the lower E(coll). If this underprediction of rovibrational excitation by the QS method is not due to PES errors and/or to non-adiabatic effects not included in the calculations, then this collision energy dependence is opposite to what might be expected based on collision complex lifetime arguments and opposite to that measured for the forward bias. While the QCT calculations captured the experimental product vibrational energy distribution better than the QS method, the QCT results underpredicted rotationally excited products, overpredicted forward-bias and predicted a trend in the strength of forward-bias with collision energy opposite to that measured, indicating that it does not completely capture the dynamic behavior measured in the experiment. Thus, these results further underscore the need for improvement in theoretical treatments of dynamics on the O3(X(1)A') PES and perhaps of the PES itself in order to better understand and predict non statistical effects in this reaction and in the formation of ozone (in which the intermediate O3* complex is collisionally stabilized by a third body). The scattering data presented here at two different collision energies provide important benchmarks to guide these improvements. PMID- 25134576 TI - Theoretical investigation of intersystem crossing between the a1A1 and X3B1 states of CH2 induced by collisions with helium. AB - Collisional energy transfer between the ground (X3B1) and first excited (a1A1) states of CH2 is facilitated by strong mixing of the rare pairs of accidentally degenerate rotational levels in the ground vibrational manifold of the [Formula: see text] state and the (020) and (030) excited bending vibrational manifolds of the X state. The simplest model for this process involves coherent mixing of the scattering T-matrix elements associated with collisional transitions within the unmixed a and X states. From previous calculations in our group, we have determined cross sections and room-temperature rate constants for intersystem crossing of CH2 by collision with He. These are used in simulations of the time dependence of the energy flow, both within and between the X and a vibronic manifolds. Relaxation proceeds through three steps: (a) rapid equilibration of the two mixed-pair levels, (b) fast relaxation within the a state, and (c) slower relaxation among the levels of the X state. Collisional transfer between the fine structure levels of the triplet (X) state is very slow. PMID- 25134577 TI - Spectral shapes of Ar-broadened HCl lines in the fundamental band by classical molecular dynamics simulations and comparison with experiments. AB - Spectral shapes of isolated lines of HCl perturbed by Ar are investigated for the first time using classical molecular dynamics simulations (CMDS). Using reliable intermolecular potentials taken from the literature, these CMDS provide the time evolution of the auto-correlation function of the dipole moment, whose Fourier Laplace transform leads to the absorption spectrum. In order to test these calculations, room temperature spectra of various lines in the fundamental band of HCl diluted in Ar are measured, in a large pressure range, with a difference frequency laser spectrometer. Comparisons between measured and calculated spectra show that the CMDS are able to predict the large Dicke narrowing effect on the shape of HCl lines and to satisfactorily reproduce the shapes of HCl spectra at different pressures and for various rotational quantum numbers. PMID- 25134578 TI - Theoretical predictions of properties and volatility of chlorides and oxychlorides of group-4 elements. I. Electronic structures and properties of MCl4 and MOCl2 (M = Ti, Zr, Hf, and Rf). AB - Relativistic, infinite order exact two-component, density functional theory electronic structure calculations were performed for MCl4 and MOCl2 of group-4 elements Ti, Zr, Hf, and element 104, Rf, with the aim to predict their behaviour in gas-phase chromatography experiments. RfCl4 and RfOCl2 were shown to be less stable than their lighter homologs in the group, tetrachlorides and oxychlorides of Zr and Hf, respectively. The oxychlorides turned out to be stable as a bent structure, though the stabilization energy with respect to the flat one (C(2v)) is very small. The trend in the formation of the tetrachlorides from the oxychlorides in group 4 is shown to be Zr < Hf < Rf, while the one in the formation of the oxychlorides from the chlorides is opposite. All the calculated properties are used to estimate adsorption energy of these species on various surfaces in order to interpret results of gas-phase chromatography experiments, as is shown in Paper II. PMID- 25134579 TI - Theoretical predictions of properties and volatility of chlorides and oxychlorides of group-4 elements. II. Adsorption of tetrachlorides and oxydichlorides of Zr, Hf, and Rf on neutral and modified surfaces. AB - With the aim to interpret results of gas-phase chromatography experiments on volatility of group-4 tetrachlorides and oxychlorides including those of Rf, adsorption enthalpies of these species on neutral, and modified quartz surfaces were estimated on the basis of relativistic, two-component Density Functional Theory calculations of MCl4, MOCl2, MCl6(-), and MOCl4(2) with the use of adsorption models. Several mechanisms of adsorption were considered. In the case of physisorption of MCl4, the trend in the adsorption energy in the group should be Zr > Hf > Rf, so that the volatility should change in the opposite direction. The latter trend complies with the one in the sublimation enthalpies, DeltaH(sub), of the Zr and Hf tetrachlorides, i.e., Zr < Hf. On the basis of a correlation between these quantities, DeltaH(sub)(RfCl4) was predicted as 104.2 kJ/mol. The energy of physisorption of MOCl2 on quartz should increase in the group, Zr < Hf < Rf, as defined by increasing dipole moments of these molecules along the series. In the case of adsorption of MCl4 on quartz by chemical forces, formation of the MOCl2 or MOCl4(2-) complexes on the surface can take place, so that the sequence in the adsorption energy should be Zr > Hf > Rf, as defined by the complex formation energies. In the case of adsorption of MCl4 on a chlorinated quartz surface, formation of the MCl6(2-) surface complexes can occur, so that the trend in the adsorption strength should be Zr <= Hf < Rf. All the predicted sequences, showing a smooth change of the adsorption energy in the group, are in disagreement with the reversed trend Zr ~ Rf < Hf, observed in the "one-atom-at-a-time" gas-phase chromatography experiments. Thus, currently no theoretical explanation can be found for the experimental observations. PMID- 25134580 TI - Vibronic coupling in asymmetric bichromophores: experimental investigation of diphenylmethane-d5. AB - Vibrationally and rotationally resolved electronic spectra of diphenylmethane-d5 (DPM-d5) are reported in the isolated-molecule environment of a supersonic expansion. While small, the asymmetry induced by deuteration of one of the aromatic rings is sufficient to cause several important effects that change the principle mechanism of vibronic coupling between the close-lying S1 and S2 states, and spectroscopic signatures such coupling produces. The splitting between S1 and S2 origins is 186 cm(-1), about 50% greater than its value in DPM d0 (123 cm(-1)), and an amount sufficient to bring the S2 zero-point level into near-resonance with the v = 1 level in the S1 state of a low-frequency phenyl flapping mode, nu(R) = 191 cm(-1). Dispersed fluorescence spectra bear clear evidence that Deltav(R) = 1 Herzberg-Teller coupling dominates the near-resonant internal mixing between the S1 and S2 manifolds. The fluorescence into each pair of Franck-Condon active ring modes shows an asymmetry that suggests incorrectly that the S1 and S2 states may be electronically localized. From rotationally resolved studies, the S0 and S1 states have been well-fit to asymmetric rotor Hamiltonians while the S2 state is perturbed and not fit. The transition dipole moment (TDM) orientation of the S1 state is nearly perpendicular to the C2 symmetry axes with 66(2)%:3(1)%:34(2)% a:b:c hybrid-type character while that of the S2 origin contains 50(10)% a:c-type (S1) and 50(10)% b-type (S2) character. A model is put forward that explains qualitatively the TDM compositions and dispersed emission patterns without the need to invoke electronic localization. The experimental data discussed here serve as a foundation for a multi-mode vibronic coupling model capable of being applied to asymmetric bichromophores, as presented in the work of B. Nebgen and L. V. Slipchenko ["Vibronic coupling in asymmetric bichromophores: Theory and application to diphenylmethane-d5," J. Chem. Phys. (submitted)]. PMID- 25134581 TI - The cyclopropene radical cation: rovibrational level structure at low energies from high-resolution photoelectron spectra. AB - The cyclopropene radical cation (c-C3H4+) is an important but poorly characterized three-membered-ring hydrocarbon. We report on a measurement of the high-resolution photoelectron and photoionization spectra of cyclopropene and several deuterated isotopomers, from which we have determined the rovibrational energy level structure of the X+ (2)B2 ground electronic state of c-C3H4+ at low energies for the first time. The synthesis of the partially deuterated isotopomers always resulted in mixtures of several isotopomers, differing in their number of D atoms and in the location of these atoms, so that the photoelectron spectra of deuterated samples are superpositions of the spectra of several isotopomers. The rotationally resolved spectra indicate a C(2v)-symmetric R0 structure for the ground electronic state of c-C3H4+. Two vibrational modes of c-C3H4+ are found to have vibrational wave numbers below 300 cm(-1), which is surprising for such a small cyclic hydrocarbon. The analysis of the isotopic shifts of the vibrational levels enabled the assignment of the lowest-frequency mode (fundamental wave number of ~110 cm(-1) in c-C3H4+) to the CH2 torsional mode (nu8+, A2 symmetry) and of the second-lowest-frequency mode (~210 cm(-1) in c-C3H4+) to a mode combining a CH out-of-plane with a CH2 rocking motion (nu15+, B2 symmetry). The potential energy along the CH2 torsional coordinate is flat near the equilibrium structure and leads to a pronounced anharmonicity. PMID- 25134582 TI - Dispersion corrected RPBE studies of liquid water. AB - The structure of liquid water has been addressed by ab initio molecular dynamics simulations based on density functional theory. Exchange-correlation effects have been described by the popular PBE and RPBE functionals within the generalized gradient approximation as these functionals also yield satisfactory results for metals which is important to model electrochemical interfaces from first principles. In addition, dispersive interactions are included by using dispersion corrected schemes. It turns out that the dispersion-corrected RPBE functional reproduces liquid water properties quite well in contrast to the PBE functional. This is caused by the replacement of the over-estimated directional hydrogen bonding in the PBE functional by non-directional dispersive interactions. PMID- 25134583 TI - Structure and aggregation in model tetramethylurea solutions. AB - The structure of model aqueous tetramethylurea (TMU) solutions is investigated employing large-scale (32,000, 64,000 particles) molecular dynamics simulations. Results are reported for TMU mole fractions, X(t), ranging from infinite dilution up to 0.07, and for two temperatures, 300 and 330 K. Two existing force fields for TMU-water solutions are considered. These are the GROMOS 53A6 united-atom TMU model combined with SPC/E water [TMU(GROMOS-UA)/W(SPC/E)], and the more frequently employed AMBER03 all-atom force field for TMU combined with the TIP3P water model [TMU(AMBER-AA)/W(TIP3P)]. It is shown that TMU has a tendency towards aggregation for both models considered, but the tendency is significantly stronger for the [TMU(AMBER-AA)/W(TIP3P)] force field. For this model signs of aggregation are detected at X(t) = 0.005, aggregation is a well established feature of the solution at X(t) = 0.02, and the aggregates increase further in size with increasing concentration. This is in agreement with at least some experimental studies, which report signals of aggregation in the low concentration regime. The TMU aggregates exhibit little structure and are simply loosely ordered, TMU-rich regions of solution. The [TMU(GROMOS-UA)/W(SPC/E)] model shows strong signs of aggregation only at higher concentrations (X(t) ? 0.04), and the aggregates appear more loosely ordered, and less well-defined than those occurring in the [TMU(AMBER-AA)/W(TIP3P)] system. For both models, TMU aggregation increases when the temperature is increased from 300 to 330 K, consistent with an underlying entropy driven, hydrophobic interaction mechanism. At X(t) = 0.07, the extra-molecular correlation length expected for microheterogeneous solutions has become comparable with the size of the simulation cell for both models considered, indicating that even the systems simulated here are sufficiently large only at low concentrations. PMID- 25134584 TI - Properties of a planar electric double layer under extreme conditions investigated by classical density functional theory and Monte Carlo simulations. AB - Monte Carlo (MC) simulation and classical density functional theory (DFT) results are reported for the structural and electrostatic properties of a planar electric double layer containing ions having highly asymmetric diameters or valencies under extreme concentration condition. In the applied DFT, for the excess free energy contribution due to the hard sphere repulsion, a recently elaborated extended form of the fundamental measure functional is used, and coupling of Coulombic and short range hard-sphere repulsion is described by a traditional second-order functional perturbation expansion approximation. Comparison between the MC and DFT results indicates that validity interval of the traditional DFT approximation expands to high ion valences running up to 3 and size asymmetry high up to diameter ratio of 4 whether the high valence ions or the large size ion are co- or counter-ions; and to a high bulk electrolyte concentration being close to the upper limit of the electrolyte mole concentration the MC simulation can deal with well. The DFT accuracy dependence on the ion parameters can be self consistently explained using arguments of liquid state theory, and new EDL phenomena such as overscreening effect due to monovalent counter-ions, extreme layering effect of counter-ions, and appearance of a depletion layer with almost no counter- and co-ions are observed. PMID- 25134585 TI - First-principles high-pressure unreacted equation of state and heat of formation of crystal 2,6-diamino-3, 5-dinitropyrazine-1-oxide (LLM-105). AB - We report dispersion-corrected density functional theoretical calculations of the unreacted equation of state (EOS) of crystal 2,6-diamino-3, 5-dinitropyrazine-1 oxide (LLM-105) under hydrostatic compression of up to 45 GPa. Convergence tests for k-points sampling in the Brillouin zone show that a 3 * 1 * 2 mesh is required to reproduce the X-ray crystal structure at ambient conditions, and we confirm our finding with a separate supercell calculation. Our high-pressure EOS yields a bulk modulus of 19.2 GPa, and indicates a tendency towards anisotropic compression along the b lattice vector due to molecular orientations within the lattice. We find that the electronic energy band gap decreases from a semiconductor type of 1.3 eV at 0 GPa to quasi-metallic type of 0.6 eV at 45 GPa. The extensive intermolecular hydrogen bonds involving the oxide (-NO) and dioxide (-NO2) interactions with the amine (-NH2) group showed enhanced interactions with increasing pressure that should be discernible in the mid IR spectral region. We do not find evidence for structural phase transitions or chemically induced transformations within the pressure range of our study. The gas phase heat of formation is calculated at the G4 level of theory to be 22.48 kcal/mol, while we obtain 25.92 kcal/mol using the ccCA-PS3 method. Density functional theory calculations of the crystal and the gas phases provided an estimate for the heat of sublimation of 32.4 kcal/mol. We thus determine the room-temperature solid heat of formation of LLM-105 to be -9.9 or -6.5 kcal/mol based on the G4 or ccCA PS3 methods, respectively. PMID- 25134586 TI - Challenges in first-principles NPT molecular dynamics of soft porous crystals: a case study on MIL-53(Ga). AB - Soft porous crystals present a challenge to molecular dynamics simulations with flexible size and shape of the simulation cell (i.e., in the NPT ensemble), since their framework responds very sensitively to small external stimuli. Hence, all interactions have to be described very accurately in order to obtain correct equilibrium structures. Here, we report a methodological study on the nanoporous metal-organic framework MIL-53(Ga), which undergoes a large-amplitude transition between a narrow- and a large-pore phase upon a change in temperature. Since this system has not been investigated by density functional theory (DFT)-based NPT simulations so far, we carefully check the convergence of the stress tensor with respect to computational parameters. Furthermore, we demonstrate the importance of dispersion interactions and test two different ways of incorporating them into the DFT framework. As a result, we propose two computational schemes which describe accurately the narrow- and the large-pore phase of the material, respectively. These schemes can be used in future work on the delicate interplay between adsorption in the nanopores and structural flexibility of the host material. PMID- 25134588 TI - Point defect weakened thermal contraction in monolayer graphene. AB - We investigate the thermal expansion behaviors of monolayer graphene and three configurations of graphene with point defects, namely the replacement of one carbon atom with a boron or nitrogen atom, or of two neighboring carbon atoms by boron-nitrogen atoms, based on calculations using first-principles density functional theory. It is found that the thermal contraction of monolayer graphene is significantly decreased by point defects. Moreover, the corresponding temperature for negative linear thermal expansion coefficient with the maximum absolute value is reduced. The cause is determined to be point defects that enhance the mechanical strength of graphene and then reduce the amplitude and phonon frequency of the out-of-plane acoustic vibration mode. Such defect weakening of graphene thermal contraction will be useful in nanotechnology to diminish the mismatching or strain between the graphene and its substrate. PMID- 25134587 TI - Lateral critical Casimir force in 2D Ising strip with inhomogeneous walls. AB - We analyze the lateral critical Casimir force acting between two planar, chemically inhomogeneous walls confining an infinite 2D Ising strip of width M. The inhomogeneity of each of the walls has size N1; they are shifted by the distance L along the strip. Using the exact diagonalization of the transfer matrix, we calculate the lateral critical Casimir force and discuss its properties, in particular its scaling close to the 2D bulk critical point, as a function of temperature, surface magnetic field, and the geometric parameters M, N1, L. We determine the magnetization profiles which display the formation of the bridge joining the inhomogeneities on the walls and establish the relation between the characteristic properties of the lateral Casimir force and magnetization morphologies. We check numerically that breaking of the bridge is related to the inflection point of the lateral force. PMID- 25134589 TI - Lone-pair interactions and photodissociation of compressed nitrogen trifluoride. AB - High-pressure behavior of nitrogen trifluoride (NF3) was investigated by Raman and IR spectroscopy at pressures up to 55 GPa and room temperature, as well as by periodic calculations up to 100 GPa. Experimentally, we find three solid-solid phase transitions at 9, 18, and 39.5 GPa. Vibrational spectroscopy indicates that in all observed phases NF3 remains in the molecular form, in contrast to the behavior of compressed ammonia. This finding is confirmed by density functional theory calculations, which also indicate that the phase transitions of compressed NF3 are governed by the interplay between lone-pair interactions and efficient molecule packing. Although nitrogen trifluoride is molecular in the whole pressure range studied, we show that it can be photodissociated by mid-IR laser radiation. This finding paves the way for the use of NF3 as an oxidizing and fluorinating agent in high-pressure reactions. PMID- 25134590 TI - Tunable electronic and optical properties of monolayer silicane under tensile strain: a many-body study. AB - The electronic structure and optical response of silicane to strain are investigated by employing first-principles calculations based on many-body perturbation theory. The bandgap can be efficiently engineered in a broad range and an indirect to direct bandgap transition is observed under a strain of 2.74%; the semiconducting silicane can even be turned into a metal under a very large strain. The transitions derive from the persistent downward shift of the lowest conduction band at the Gamma-point upon an increasing strain. The quasi-particle bandgaps of silicane are sizable due to the weak dielectric screening and the low dimension; they are rapidly reduced as strain increases while the exciton bound energy is not that sensitive. Moreover, the optical absorption edge of the strained silicane significantly shifts towards a low photon energy region and falls into the visible light range, which might serve as a promising candidate for optoelectronic devices. PMID- 25134591 TI - Hydrogen adsorption in metal-organic frameworks: the role of nuclear quantum effects. AB - The role of nuclear quantum effects on the adsorption of molecular hydrogen in metal-organic frameworks (MOFs) has been investigated on grounds of Grand Canonical Quantized Liquid Density-Functional Theory (GC-QLDFT) calculations. For this purpose, we have carefully validated classical H2-host interaction potentials that are obtained by fitting Born-Oppenheimer ab initio reference data. The hydrogen adsorption has first been assessed classically using Liquid Density-Functional Theory and the Grand-Canonical Monte Carlo methods. The results have been compared against the semi-classical treatment of quantum effects by applying the Feynman-Hibbs correction to the Born-Oppenheimer-derived potentials, and by explicit treatment within the GC-QLDFT. The results are compared with experimental data and indicate pronounced quantum and possibly many particle effects. After validation calculations have been carried out for IRMOF-1 (MOF-5), GC-QLDFT is applied to study the adsorption of H2 in a series of MOFs, including IRMOF-4, -6, -8, -9, -10, -12, -14, -16, -18, and MOF-177. Finally, we discuss the evolution of the H2 quantum fluid with increasing pressure and lowering temperature. PMID- 25134592 TI - Density functional theory study of CO-induced segregation in gold-based alloys. AB - This paper reports a systematic study of the effect of CO gas on the chemical composition at the surface of gold-based alloys. Using DFT periodic calculations in presence of adsorbed CO the segregation behavior of group 9-10-11 transition metals (Ag, Cu, Pt, Pd, Ni, Ir, Rh, Co) substituted in semi-infinite gold surfaces is investigated. Although, CO is found to be more strongly adsorbed on (100) than on the (111) surface, the segregation of M impurities is found to be more pronounced on the (111) surface. The results reveal two competitive effects: the effect of M on CO and the effect of CO on M. Thus, on one hand, if M exists on the (100) gold facet, CO would be strongly adsorbed on it. But if M is initially located in the bulk, it would segregate to the (111) facet instead of the (100) in order to bind to CO. PMID- 25134593 TI - Multi-scale times and modes of fast and slow relaxation in solutions with coexisting spherical and cylindrical micelles according to the difference Becker Doring kinetic equations. AB - The eigenvalues and eigenvectors of the matrix of coefficients of the linearized kinetic equations applied to aggregation in surfactant solution determine the full spectrum of characteristic times and specific modes of micellar relaxation. The dependence of these relaxation times and modes on the total surfactant concentration has been analyzed for concentrations in the vicinity and well above the second critical micelle concentration (cmc2) for systems with coexisting spherical and cylindrical micelles. The analysis has been done on the basis of a discrete form of the Becker-Doring kinetic equations employing the Smoluchowsky diffusion model for the attachment rates of surfactant monomers to surfactant aggregates with matching the rates for spherical aggregates and the rates for large cylindrical micelles. The equilibrium distribution of surfactant aggregates in solution has been modeled as having one maximum for monomers, another maximum for spherical micelles and wide slowly descending branch for cylindrical micelles. The results of computations have been compared with the analytical ones known in the limiting cases from solutions of the continuous Becker-Doring kinetic equation. They demonstrated a fair agreement even in the vicinity of the cmc2 where the analytical theory looses formally its applicability. PMID- 25134594 TI - Simulation of electric double layers around charged colloids in aqueous solution of variable permittivity. AB - The ion distribution around charged colloids in solution has been investigated intensely during the last decade. However, few theoretical approaches have included the influence of variation in the dielectric permittivity within the system, let alone in the surrounding solvent. In this article, we introduce two relatively new methods that can solve the Poisson equation for systems with varying permittivity. The harmonic interpolation method approximately solves the Green's function in terms of a spherical harmonics series, and thus provides analytical ion-ion potentials for the Hamiltonian of charged systems. The Maxwell equations molecular dynamics algorithm features a local approach to electrostatics, allowing for arbitrary local changes of the dielectric constant. We show that the results of both methods are in very good agreement. We also found that the renormalized charge of the colloid, and with it the effective far field interaction, significantly changes if the dielectric properties within the vicinity of the colloid are changed. PMID- 25134595 TI - Bilayer registry in a multicomponent asymmetric membrane: dependence on lipid composition and chain length. AB - A question of considerable interest to cell membrane biology is whether phase segregated domains across an asymmetric bilayer are strongly correlated with each other and whether phase segregation in one leaflet can induce segregation in the other. We answer both these questions in the affirmative, using an atomistic molecular dynamics simulation to study the equilibrium statistical properties of a 3-component asymmetric lipid bilayer comprising an unsaturated palmitoyl-oleoyl phosphatidyl-choline, a saturated sphingomyelin, and cholesterol with different composition ratios. Our simulations are done by fixing the composition of the upper leaflet to be at the coexistence of the liquid ordered (l(o))-liquid disordered (l(d)) phases, while the composition of the lower leaflet is varied from the phase coexistence regime to the mixed l(d) phase, across a first-order phase boundary. In the regime of phase coexistence in each leaflet, we find strong transbilayer correlations of the l(o) domains across the two leaflets, resulting in bilayer registry. This transbilayer correlation depends sensitively upon the chain length of the participating lipids and possibly other features of lipid chemistry, such as degree of saturation. We find that the l(o) domains in the upper leaflet can induce phase segregation in the lower leaflet, when the latter is nominally in the mixed (l(d)) phase. PMID- 25134596 TI - Molar mass and temperature dependence of the thermodiffusion of polyethylene oxide in water/ethanol mixtures. AB - In this work, we study the molar mass dependence of the thermodiffusion of polyethylene oxide at different temperatures in ethanol, water/ethanol mixture (c(water) = 0.7), and water in a molar mass range up to M(w) = 180,000 g/mol. Due to the low solubility of polyethylene oxide oligomers in ethanol the measurements are limited up to M(w) = 2200 g/mol. The specific water/ethanol concentration 0.7 has been chosen, because at this weight fraction the thermal diffusion coefficient, D(T), of water/ethanol vanishes so that the system can be treated as a pseudo binary mixture. The addition of ethanol will degrade the solvent quality, so that we expect a change of the interaction energies between polymer and solvent. The analysis of the experimental data within a theoretical model shows the need of a refined model, which takes specific interactions into account. PMID- 25134597 TI - Isolating the non-polar contributions to the intermolecular potential for water alkane interactions. AB - Intermolecular potential models for water and alkanes describe pure component properties fairly well, but fail to reproduce properties of water-alkane mixtures. Understanding interactions between water and non-polar molecules like alkanes is important not only for the hydrocarbon industry but has implications to biological processes as well. Although non-polar solutes in water have been widely studied, much less work has focused on water in non-polar solvents. In this study we calculate the solubility of water in different alkanes (methane to dodecane) at ambient conditions where the water content in alkanes is very low so that the non-polar water-alkane interactions determine solubility. Only the alkane-rich phase is simulated since the fugacity of water in the water rich phase is calculated from an accurate equation of state. Using the SPC/E model for water and TraPPE model for alkanes along with Lorentz-Berthelot mixing rules for the cross parameters produces a water solubility that is an order of magnitude lower than the experimental value. It is found that an effective water Lennard Jones energy epsilon(W)/k = 220 K is required to match the experimental water solubility in TraPPE alkanes. This number is much higher than used in most simulation water models (SPC/E-epsilon(W)/k = 78.2 K). It is surprising that the interaction energy obtained here is also higher than the water-alkane interaction energy predicted by studies on solubility of alkanes in water. The reason for this high water-alkane interaction energy is not completely understood. Some factors that might contribute to the large interaction energy, such as polarizability of alkanes, octupole moment of methane, and clustering of water at low concentrations in alkanes, are examined. It is found that, though important, these factors do not completely explain the anomalously strong attraction between alkanes and water observed experimentally. PMID- 25134598 TI - Rotational Brownian dynamics simulations of clathrin cage formation. AB - The self-assembly of nearly rigid proteins into ordered aggregates is well suited for modeling by the patchy particle approach. Patchy particles are traditionally simulated using Monte Carlo methods, to study the phase diagram, while Brownian Dynamics simulations would reveal insights into the assembly dynamics. However, Brownian Dynamics of rotating anisotropic particles gives rise to a number of complications not encountered in translational Brownian Dynamics. We thoroughly test the Rotational Brownian Dynamics scheme proposed by Naess and Elsgaeter [Macromol. Theory Simul. 13, 419 (2004); Naess and Elsgaeter Macromol. Theory Simul. 14, 300 (2005)], confirming its validity. We then apply the algorithm to simulate a patchy particle model of clathrin, a three-legged protein involved in vesicle production from lipid membranes during endocytosis. Using this algorithm we recover time scales for cage assembly comparable to those from experiments. We also briefly discuss the undulatory dynamics of the polyhedral cage. PMID- 25134599 TI - The role of non-equilibrium fluxes in the relaxation processes of the linear chemical master equation. AB - We propose a non-equilibrium thermodynamical description in terms of the Chemical Master Equation (CME) to characterize the dynamics of a chemical cycle chain reaction among m different species. These systems can be closed or open for energy and molecules exchange with the environment, which determines how they relax to the stationary state. Closed systems reach an equilibrium state (characterized by the detailed balance condition (D.B.)), while open systems will reach a non-equilibrium steady state (NESS). The principal difference between D.B. and NESS is due to the presence of chemical fluxes. In the D.B. condition the fluxes are absent while for the NESS case, the chemical fluxes are necessary for the state maintaining. All the biological systems are characterized by their "far from equilibrium behavior," hence the NESS is a good candidate for a realistic description of the dynamical and thermodynamical properties of living organisms. In this work we consider a CME written in terms of a discrete Kolmogorov forward equation, which lead us to write explicitly the non equilibrium chemical fluxes. For systems in NESS, we show that there is a non conservative "external vector field" whose is linearly proportional to the chemical fluxes. We also demonstrate that the modulation of these external fields does not change their stationary distributions, which ensure us to study the same system and outline the differences in the system's behavior when it switches from the D.B. regime to NESS. We were interested to see how the non-equilibrium fluxes influence the relaxation process during the reaching of the stationary distribution. By performing analytical and numerical analysis, our central result is that the presence of the non-equilibrium chemical fluxes reduces the characteristic relaxation time with respect to the D.B. condition. Within a biochemical and biological perspective, this result can be related to the "plasticity property" of biological systems and to their capabilities to switch from one state to another as is observed during synaptic plasticity, cell fate determination, and differentiation. PMID- 25134604 TI - A comparison of risk factors for hepatitis C among young and older adult prisoners. AB - Internationally, the prevalence of hepatitis C infection is higher among prisoners when compared to the general population, particularly among people who inject drugs. This study estimates the prevalence of, and compares the risk factors for, hepatitis C in young (< 25 years) and older (>= 25 years) prisoners with a history of injection drug use. Participants were 677 sentenced prisoners in Queensland, Australia, with a lifetime history of injection drug use, recruited in the 6 weeks prior to release from custody. The prevalence of hepatitis C exposure was significantly lower in young prisoners than in older prisoners (20.7% vs. 29.4%, p = .03). Risk factors for hepatitis C varied between young and older prisoners. Young people who inject drugs and who have had shorter time at risk of hepatitis C exposure are an important target group for hepatitis C prevention efforts. PMID- 25134605 TI - Observation of a rare earth ion-extractant complex arrested at the oil-water interface during solvent extraction. AB - Selective extraction of metal ions from a complex aqueous mixture into an organic phase is used to separate toxic or radioactive metals from polluted environments and nuclear waste, as well as to produce industrially relevant metals, such as rare earth ions. Selectivity arises from the choice of an extractant amphiphile, dissolved in the organic phase, which interacts preferentially with the target metal ion. The extractant-mediated process of ion transport from an aqueous to an organic phase takes place at the aqueous-organic interface; nevertheless, little is known about the molecular mechanism of this process despite its importance. Although state-of-the-art X-ray scattering is uniquely capable of probing molecular ordering at a liquid-liquid interface with subnanometer spatial resolution, utilizing this capability to investigate interfacial dynamical processes of short temporal duration remains a challenge. We show that a temperature-driven adsorption transition can be used to turn the extraction on and off by controlling adsorption and desorption of extractants at the oil-water interface. Lowering the temperature through this transition immobilizes a supramolecular ion-extractant complex at the interface during the extraction of rare earth erbium ions. Under the conditions of these experiments, the ion extractant complexes condense into a two-dimensional inverted bilayer, which is characterized on the molecular scale with synchrotron X-ray reflectivity and fluorescence measurements. Raising the temperature above the transition leads to Er ion extraction as a result of desorption of ion-extractant complexes from the interface into the bulk organic phase. XAFS measurements of the ion-extractant complexes in the bulk organic phase demonstrate that they are similar to the interfacial complexes. PMID- 25134606 TI - Interfacial load transfer in polymer/carbon nanotube nanocomposites with a nanohybrid shish kebab modification. AB - Interfacial properties are known to have a critical effect on the mechanical properties of a nanocomposite material system. Here, the interfacial load transfer in a carbon nanotube (CNT)/nylon-11 composite was studied with a CNT/nylon-11 nanohybrid shish kebab (NHSK) structure modification using Raman spectroscopy. Characterization of the polymer crystal in the NHSK using differential scanning calorimetry (DSC) for the first time indicates that the NHSK structure formed a more perfect crystal structure than the bulk polymer. On the basis of transmission electron microscopy and DSC results, a new growth model for the NHSK crystal is hypothesized, indicating the formation of an initial uniform crystal layer on the CNT prior to the crystallization of the kebabs. Characterization of the nanocomposites using Raman spectroscopy, with the samples heated to introduce interfacial shear stress caused by thermal expansion mismatch, found that the D* band of the CNT in the NHSK/nylon-11 composite displayed a more pronounced shift with an increase in temperature, which is attributed to the NHSK structure being more effective at transferring load from the nylon matrix to the nanotube inclusions. The NHSK structure was also used to fabricate composites with two amorphous polymers, polycarbonate and poly(methyl methacrylate), to investigate the load transfer mechanism. It was found that when the compatibility between the polymer in the NHSK structure and the bulk polymer matrix at the molecular level is sufficiently high, the ensuing mechanical interlocking effect further enhances the interfacial load transfer for polymer nanocomposites. Additional mechanical characterization of polymer nanocomposites with 0.1 wt % NHSK reinforcement demonstrates how the moduli and ultimate tensile strength of the nanocomposites can be improved via this NHSK structure. PMID- 25134609 TI - An-jun-ning, a traditional herbal formula, attenuates spontaneous withdrawal symptoms via modulation of the dopamine system in morphine-dependent rats. AB - BACKGROUND: The dopamine system, which is involved in drug dependence, can be damaged by opioid abuse. However, current clinical medicines cannot reverse these damages in the brain, which are believed to be a key reason for the high relapse rate after abstinence treatment. This study aimed to investigate the effects of An-jun-ning (AJN), a commercial traditional Chinese medicine formula used for the treatment of opioid addiction, on the dopamine system in morphine-dependent rats and to explore the possible mechanism underlying its therapeutic effects. METHODS: The morphine dependence model was obtained through injections of morphine at increasing doses for 8 days. The AJN pre-treatment group was administered AJN 30 min before each morphine administration, and the AJN post treatment groups were treated with AJN for 10 days after withdrawal. Spontaneous withdrawal symptoms (wet dog shakes, and episodes of writhing) were observed after withdrawal. Autoradiography study and/or immunohistochemical staining were used to examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and tyrosine hydroxylase (TH). RESULTS: (1) Pre-treatment with AJN attenuates wet dog shakes and episodes of writhing to approximately 50% or less of those observed in the morphine group (p < 0.01). (2) AJN post-treatment dose dependently reduced the number of wet dog shakes (p < 0.01), and the episodes of writhing (p < 0.01). (3) Pre-treatment with AJN effectively interdicted the morphine-induced decreases in the levels of DAT, D2R, and TH in the striatum (p < 0.01) such that they remained at nearly normal levels. (4) Post-treatment with AJN restored DAT and D2R to the normal levels (p < 0.01) and the level of TH to 87% of normal in the striatum. CONCLUSIONS: AJN can effectively alleviate opioid withdrawal symptoms and preserve or restore the DAT, D2R, and TH levels in the striatum. The mechanism underlying the effect of AJN on withdrawal symptoms may be related to the modulation of the dopamine system by AJN. These results suggest that AJN may help to prevent relapse in opioid dependence treatment. PMID- 25134619 TI - Host response: new LPS receptors discovered. PMID- 25134617 TI - Interplay between phosphorylation and SUMOylation events determines CESTA protein fate in brassinosteroid signalling. AB - Brassinosteroids (BRs) are steroid hormones that are essential for plant growth. Responses to these hormones are mediated by transcription factors of the bri1-EMS suppressor 1/brassinazole resistant 1 subfamily, and BRs activate these factors by impairing their inhibitory phosphorylation by GSK3/shaggy-like kinases. Here we show that BRs induce nuclear compartmentalization of CESTA (CES), a basic helix-loop-helix transcription factor that regulates BR responses, and reveal that this process is regulated by CES SUMOylation. We demonstrate that CES contains an extended SUMOylation motif, and that SUMOylation of this motif is antagonized by phosphorylation to control CES subnuclear localization. Moreover, we provide evidence that phosphorylation regulates CES transcriptional activity and protein turnover by the proteasome. A coordinated modification model is proposed in which, in a BR-deficient situation, CES is phosphorylated to activate target gene transcription and enable further posttranslational modification that controls CES protein stability and nuclear dynamics. PMID- 25134618 TI - Master recyclers: features and functions of bacteria associated with phytoplankton blooms. AB - Marine phytoplankton blooms are annual spring events that sustain active and diverse bloom-associated bacterial populations. Blooms vary considerably in terms of eukaryotic species composition and environmental conditions, but a limited number of heterotrophic bacterial lineages - primarily members of the Flavobacteriia, Alphaproteobacteria and Gammaproteobacteria - dominate these communities. In this Review, we discuss the central role that these bacteria have in transforming phytoplankton-derived organic matter and thus in biogeochemical nutrient cycling. On the basis of selected field and laboratory-based studies of flavobacteria and roseobacters, distinct metabolic strategies are emerging for these archetypal phytoplankton-associated taxa, which provide insights into the underlying mechanisms that dictate their behaviours during blooms. PMID- 25134620 TI - A systematic review on the affordability of a healthful diet for families in the United States. AB - OBJECTIVES: As obesity rates remain alarmingly high, the importance of healthful diets is emphasized; however, affordability of such diets is disputed. Market basket surveys (MBSs) investigate the affordability of diets for families that meet minimum daily dietary requirements using actual food prices from grocery stores. This review paper describes the methods of MBSs, summarizes methodology, price and affordability findings, limitations, and suggests related policy and practice implications. DESIGN AND SAMPLE: This is a systematic review of 16 MBSs performed in the United States from 1985 to 2012. A comprehensive multidisciplinary database search strategy was used to identify articles meeting inclusion criteria. RESULTS: Results indicated MBS methodology varied across studies and price data indicated healthful diets for families are likely unaffordable when purchased from small- to medium-sized stores and may be unaffordable in larger stores when compared to the Thrifty Food Plan. CONCLUSIONS: Using a social ecological approach, public health nurses and all public health professionals are prime advocates for increased affordability of healthful foods. This study includes policy advocacy, particularly in support of Supplemental Nutrition Assistance Program benefits for low-income families. Future research implications are provided, including methodological recommendations for consistency and quality of forthcoming MBS research. PMID- 25134621 TI - Comparison of programs for determining temporal-spatial gait variables from instrumented walkway data: PKmas versus GAITRite. AB - BACKGROUND: Measurement of temporal-spatial gait variables is common in aging research with several methods available. This study investigated the differences in temporal-spatial gait outcomes derived from two different programs for processing instrumented walkway data. METHOD: Data were collected with GAITRite(r) hardware from 86 healthy older people and 44 older people four months following surgical repair of hip fracture. Temporal-spatial variables were derived using both GAITRite(r) and PKmas(r) processing programs from the same raw footfall data. RESULTS: The mean differences between the two programs for most variables were negligible, including for Speed (mean difference 0.3 +/- 0.6 cm/sec, or 0.3% of the mean GAITRite(r) Speed). The mean absolute percentage difference for all 18 gait variables examined ranged from 0.04% for Stride Duration to 66% for Foot Angle. The ICCs were almost perfect (>=0.99) for all variables apart from Base Width, Foot Angle, Stride Length Variability, Step Length Variability, Step Duration Variability and Step Width Variability, which were all never-the-less above 0.84. There were systematic differences for Base Width (PKmas(r) values 1.6 cm lower than GAITRite(r)) and Foot Angle (PKMAS(r) values 0.7 degrees higher than GAITRite(r)). The differences can be explained by the differences in definitions and calculations between the programs. CONCLUSIONS: The study demonstrated that for most variables the outcomes from both programs can be used interchangeably for evaluation of gait among older people collected with GAITRite(r) hardware. However, validity and reliability for Base Width and Foot Angle derived by PKMAS(r) would benefit from further investigation. PMID- 25134622 TI - Positive and negative experiences of breast pumping during the first 6 months. AB - For mothers with breastfeeding difficulties, pumping can be recommended to help establish milk production. However, pumping may present some barriers to successful breastfeeding. Mothers with milk supply concern may be at higher risk of barriers to successful breastfeeding. No previous studies have described experiences of pumping among mothers with milk supply concern. We conducted 10 focus groups of 56 mothers who had milk supply concern in the first month after birth. A paid, trained facilitator led groups in a semi-structured approach. Sessions were audiorecorded and transcribed verbatim. The transcripts were coded independently by two investigators and analysed using grounded theory. We identified five themes related to the experience of pumping among mothers with milk supply concern: (1) additional control over breastfeeding from pumping: 'I would feed and then give him ... whatever I could manage to pump to him'. (2) Painful experience: 'The first time I pumped my boobs hurt so bad'. (3) Pumped volume affected milk supply concern: 'Pump and there was hardly anything coming out that's when I started to worry'. (4) Pumping interfered with other nurturing activities: 'While you're pumping, you can't touch the baby'. (5) Frustration from inconsistent provider advice: 'They told me to pump ... and then said, "That's going to cause your milk to increase too much" '. Mothers had positive and negative experiences with pumping. Clinicians should assess a mother's experience shortly after she initiates pumping, as further management and counselling may be necessary to avoid barriers to successful breastfeeding. PMID- 25134623 TI - Calcium supplementation in chronic kidney disease. AB - INTRODUCTION: There is high prevalence of calcium supplementation in the general population and some recent data suggest that this may increase the risk of vascular calcification. Calcium-based binders have been a standard treatment for hyperphosphatemia in patients with chronic kidney disease (CKD). Though as effective as phosphate binders, they provide a source of substantial calcium intake. AREAS COVERED: In addition to the balance studies recently completed to assess the implications of calcium loading in CKD, we also review observational studies and clinical trials involving calcium-based binders. Clinically significant endpoints such as vascular calcification, mortality and bone morphology were evaluated. The existing data are concerning for the role of calcium supplementation and calcium binder use in patients with renal compromise. EXPERT OPINION: There are few guidelines on advised calcium intake in patients with renal failure; however, on the basis of existing data, it may be safer to have the upper limit of calcium intake (including that of supplementation/binder use) up to 1 g. The old Kidney Disease Outcomes Quality Initiative suggestion of limiting the calcium intake to 2 g may need to be reconsidered. PMID- 25134624 TI - Author's response. PMID- 25134625 TI - Autonomous basin climbing method with sampling of multiple transition pathways: application to anisotropic diffusion of point defects in hcp Zr. AB - This paper presents an extension of the autonomous basin climbing (ABC) method, an atomistic activation-relaxation technique for sampling transition-state pathways. The extended algorithm (ABC-E) allows the sampling of multiple transition pathways from a given minimum, with the additional feature of identifying the pathways in the order of increasing activation barriers, thereby prioritizing them according to their importance in the kinetics. Combined with on the-fly kinetic Monte Carlo calculations, the method is applied to simulate the anisotropic diffusion of point defects in hcp Zr. Multiple migration mechanisms are identified for both the interstitials and vacancies, and benchmarked against results from other methods in the literature. The self-interstitial atom (SIA) diffusion kinetics shows a maximum anisotropy at intermediate temperatures (400~700 K), a non-monotonic behavior that we explain to originate from the stabilities and migration mechanisms associated with different SIA sites. The accuracy of the ABC-E calculations is validated, in part, by the existing results in the literature for point defect diffusion in hcp Zr, and by benchmarking against analytical results on a hypothetical rough-energy landscape. Lastly, sampling prioritization and computational efficiency are demonstrated through a direct comparison between the ABC-E and the activation relaxation technique. PMID- 25134626 TI - Anomalous orientations of a rigid carbon nanotube in a sheared fluid. AB - The nanoparticle orientation in fluid systems can be correlated with the rotational diffusion and is widely used to tune the physical properties of functional materials. In the current work, the controllability of the orientation of a single rigid carbon nanotube in a fluid is investigated by imposing a linear shear flow. Molecular dynamics simulations reveal three forms of anomalous behavior: (i) "Aligned orientation" when the nanotube oscillates around a particular direction which is close to the flow direction at a small angle of about 10 degrees in the velocity-gradient plane; (ii) "Interrupted orientation" when the oscillation is interrupted by a 360 degrees rotation now and then; (iii) "Random orientation" when 360 degrees rotations dominate with the rotational direction coinciding with the local fluid flow direction. The orientation order is a function of the Peclet number (Pe). The results show that the correlation between Pe and the orientation order from the two-dimensional model does not apply to the three-dimensional cases, perhaps due to some anomalous behavior and cross-section effects. This work provides clear pictures of the nanoparticle movement that can be used to guide particle manipulation techniques. PMID- 25134628 TI - [Working conditions for supermarket employees: from experimental data to best practices]. AB - BACKGROUND: Thermal, acoustic and visual comfort conditions for hypermarket workers have never been investigated with scientific methods. OBJECTIVES: taking advantage of a case study, with characteristics capable of generalizing the results, analytically measure the actual comfort conditions to which workers are exposed and point out possible ameliorative proposals. METHODS: Carry out a detailed survey based on instrumental measurements combined with subjective questionnaires to assess the indoor environment. RESULTS: Even though the analysis pointed out no significant risk conditions, several smaller problems appeared in terms of local discomfort (such as cold limbs, higher sound level exposure, limited glare phenomena) for cashier workers. The origin of these problems appeared to be the pivotal position of the cash registers. CONCLUSIONS: Taking into account observed phenomena and their causes a list of "best practices" has been defined hoping that their adoption could further limit any impact on workers comfort conditions. PMID- 25134630 TI - [Musculoskeletal disorders and work-related injuries among hospital day- and shift workers]. AB - BACKGROUND: Most research findings show that shift-and night work are associated with cardiovascular, musculoskeletal and neurological disorders as well as work related injuries among health care workers. OBJECTIVES: This sample based study on 246 hospital workers was performed to determine whether shift work may affect musculoskeletal disorders and injury risk. METHODS: During the health surveillance program, data were collected by means of the Nordic questionnaire and the risk evaluation document. RESULTS AND CONCLUSIONS: A sample of 134 shift workers was compared to a sample of 112 day workers. Hospital day workers were found to be at greater risk of musculoskeletal symptoms in single or multiple body sites than shift workers. The prevalence of symptoms in the low back (63% vs 50%), neck (54% vs 42%) and upper extremities (26% vs 12%) was significantly higher in day workers than shift workers. In particular, among day nurses the prevalence of complaints in the upper extremities was more elevated (p<0,01) than nurses working in shifts; whereas, technicians working during the day reported more frequently symptoms in the neck (p<0,05) than technicians working in shifts. However, the average age and work experience were significantly higher in day workers than shift workers. Furthermore, the study showed that nursing personnel was at great risk of sustaining an occupational musculoskeletal injury, especially for nurses working in shifts on medical and surgical wards. Data suggest that, concerning shift work planning, it is important to consider the workload according to activity. PMID- 25134629 TI - A rare occupation causing mesothelioma: mechanisms and differential etiology. AB - BACKGROUND: In a mesothelioma lawsuit, the Public Prosecutor commissioned an expert evidence on the legal accountability for the disease, because the patient experienced multiple exposures to asbestos in both occupational and environmental settings. OBJECTIVES: To collect information on asbestos exposure from all available sources and to quantify the contribution of each source of exposure as a percentage of the total risk. METHODS: We retrieved information on jobs done and asbestos exposure from a work colleague and a database maintained by the National Institute for Insurance of Occupational Accidents/Diseases, respectively. Information on environmental exposure was searched through the scientific literature. The contribution of each source of exposure was quantified with a method of risk apportionment, taking into account time elapsed since first and last exposure, intensity and frequency of exposure and carcinogenic potency of asbestos fiber mix. RESULTS: The subject worked in the maintenance of railway electrification system. The mechanical compression stress induced on the ballast during passage of trains released chrysotile (from fragmented stones) and crocidolite (through abrasive action of crushed gravel on the underbody of rolling stocks insulated with friable crocidolite). Despite the low cumulative exposure (about 2 ff*years/cc), 99% of the mesothelioma risk was attributable to the work done because of the high content of crocidolite of inhaled asbestos. CONCLUSIONS: The report of an uncommon source of occupational asbestos exposure and a scientifically based method to allocate mesothelioma risk among multiple exposure could help to recognize mesothelioma as occupational disease in the workers employed in maintenance of the railway electrification system under the Italian National Railways. PMID- 25134631 TI - [Foot and ankle ability measure: cross-cultural translation and validation of the Italian version of the ADL module (FAAM-I/ADL)]. AB - BACKGROUND: Valid and reliable outcome measures are fundamental for evaluating and comparing the effects of rehabilitation. Among the different tools used for the assessment of musculoskeletal disorders of the lower limb, the Foot and Ankle Ability Measure (FAAM) has been shown to have good psychometric properties. However, it has not yet been translated into Italian. The module regarding the performance of daily living activities (FAAM/ADL), in particular, can be applied also in an occupational setting. OBJECTIVE: To obtain an Italian version of the FAAM, and to validate the FAAM-I/ADL. METHODS: The cultural adaptation was performed according to international guidelines for forward/backward translation. The activities of daily living (ADL) module of the FAAM-I (FAAM-I/ADL) was validated with classical test theory methods in a convenience sample of 57 patients. Different parameters were calculated: internal consistency (Cronbach's alpha and item-to-total correlation); criterion validity, through Pearson's correlation (r) with the Lower Extremity Functional Scale (LEFS); test-retest reliability (ICC2,1); Standard Error of Measurement (SEM); and Minimal Detectable Change (MDC95). RESULTS: The statistical analysis showed good internal consistency (Cronbach's alpha=.96, item-to-total correlation ranged between .51 and .85), high criterion validity (r=.66, p<0.01) and excellent test-retest reliability (ICC2, 1=.98, CI95%=.97-.99). The SEM was 2.7 points, with a MDC95 of 7.5 points. CONCLUSIONS: FAAM-I/ADL shows good psychometric properties, together with speed and ease of administration and scoring. Its use will facilitate the comparison of Italian data with international studies, ensuring greater uniformity of assessment. PMID- 25134627 TI - DNA demethylation and invasive cancer: implications for therapeutics. AB - One of the hallmarks of cancer is aberrant DNA methylation, which is associated with abnormal gene expression. Both hypermethylation and silencing of tumour suppressor genes as well as hypomethylation and activation of prometastatic genes are characteristic of cancer cells. As DNA methylation is reversible, DNA methylation inhibitors were tested as anticancer drugs with the idea that such agents would demethylate and reactivate tumour suppressor genes. Two cytosine analogues, 5-azacytidine (Vidaza) and 5-aza-2'-deoxycytidine, were approved by the Food and Drug Administration as antitumour agents in 2004 and 2006 respectively. However, these agents might cause activation of a panel of prometastatic genes in addition to activating tumour suppressor genes, which might lead to increased metastasis. This poses the challenge of how to target tumour suppressor genes and block cancer growth with DNA-demethylating drugs while avoiding the activation of prometastatic genes and precluding the morbidity of cancer metastasis. This paper reviews current progress in using DNA methylation inhibitors in cancer therapy and the potential promise and challenges ahead. PMID- 25134632 TI - [The safety data sheets of the paint and coatings sector: analysis of the items of most interest to health and safety in the workplace]. AB - INTRODUCTION: The interlinked REACH-CLP regulations promote the sharing of knowledge regarding the risks and hazards of chemicals throughout the supply chain. The safety data sheet (SDS) is the main instrument to achieve this goal. OBJECTIVE: to study 100 SDS of paints and coatings sector in order to highlight major criticisms related to health and safety of workers. MATERIALS AND METHODS: Using the criteria prescribed by Regulation 453/2010/EC and preparing a suitable check list, some items of the sections 1 "Identification of the substance/mixture and of the company", 2 "Hazards identification", 3 "Composition/information on ingredients", the first part of section 7 "Precautions for safe handling", sections 8 "Exposure controls/personal protection" and 16 "Other information", were therefore evaluated for their appropriateness. RESULTS: Seven SDS were written in a foreign language and were excluded from further analysis. Of the remaining 93 SDS, only 23% had a proportion of adequate items greater than 80%, 49 % had adequate items between 60 and 80%, and 28% had less than 60% adequate items. The most critical sections were those relating to workers' safe handling and exposure controls and protection. CONCLUSION: In conclusion, from the analysis of SDS we found high percentages of inadequacy, especially in sections 7 and 8, the most relevant for the protection of the health and safety of workers. PMID- 25134633 TI - [Counterproductive behaviors and moral disengagement of nurses as potential consequences of stress-related work: validity and reliability of measurement scales]. AB - BACKGROUND: Several studies, but no one in the nursing, have shown that work stress can facilitate the adoption of specific behaviors that the literature identifies as Counterproductive Work Behaviors (CWB). Individuals, however, not giving up to their moral principles, may transgress social, organizational, moral and ethical norms, through the adoption of moral disengagement (MD). OBJECTIVES: The purpose of this study is to validate two specific scales of deviant behaviors and MD in nursing: the Nursing Counterproductive Work Behaviours Scale (Nursing CWBS) and Nursing Moral Disengagement Scale (Nursing MDS). METHOD: 460 nurses participated in the study. After the adaptation of the Counterproductive Work Behavior Checklist by Spector and Fox to Nursing context (Nursing CWBS) and the ex novo development of the Nursing MDS, the psychometric properties of the two scales were tested. Also, the two scales were correlated. RESULTS: Through a cross-validation approach and based on the results of exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), we have shown that the scales have good psychometric properties. Furthermore, the results, attest that the nurse with high levels of MD implements more CWB in the workplace. CONCLUSIONS: The Nursing CWBS and Nursing MDS represent a valid starting point for the study of such phenomena in this specific context where stress among nursing staff is sometimes of considerable extent, especially in specific contexts of clinical care. PMID- 25134634 TI - Work-related musculoskeletal disorders in nursing: current knowledge and ongoing challenges for occupational health. AB - Work-related Musculoskeletal Disorders (MSD) represent a major occupational health concern when considering the relationships between work and disease but associations between MSD and hospital work, especially in the nursing profession, aren't yet full understanded.QMSDuestions that still need to be answered include: Are nurses' work-related musculoskeletal symptoms and injuries dependent on the wards, the hospital organization and even the national occupational health policies that they originated from? Is their MSD related with workplaces demands, equipment, and nurse-patient ratios? Do these factors highlight different nursing occupational exposure to MSD hazards? What are the individual and psychosocial contributes to nurses WRMSDs in different nursing contexts? As such, a new approach which integrates more realistic working conditions, real hospital equipment, workplace features, and individual information would likely be a better way forwards in the addressing the current MSD epidemic among hospital nurses, worldwide...... PMID- 25134636 TI - Cost-effectiveness of health promotion targeting physical activity and healthy eating in mental health care. AB - BACKGROUND: There is a higher prevalence of obesity in individuals with mental disorders compared to the general population. The results of several studies suggested that weight reduction in this population is possible following psycho educational and/or behavioural weight management interventions. Evidence of the effectiveness alone is however inadequate for policy making. The aim of the current study was to evaluate the cost-effectiveness of a health promotion intervention targeting physical activity and healthy eating in individuals with mental disorders. METHODS: A Markov decision-analytic model using a public payer perspective was applied, projecting the one-year results of a 10-week intervention over a time horizon of 20 years, assuming a repeated yearly implementation of the programme. Scenario analysis was applied evaluating the effects on the results of alternative modelling assumptions. One-way sensitivity analysis was performed to assess the effects on the results of varying key input parameters. RESULTS: An incremental cost-effectiveness ratio of 27,096?/quality adjusted life years (QALY) in men, and 40,139?/QALY in women was found in the base case. Scenario analysis assuming an increase in health-related quality of life as a result of the body mass index decrease resulted in much better cost effectiveness in both men (3,357?/QALY) and women (3,766?/QALY). The uncertainty associated with the intervention effect had the greatest impact on the model. CONCLUSIONS: As far as is known to the authors, this is the first health economic evaluation of a health promotion intervention targeting physical activity and healthy eating in individuals with mental disorders. Such research is important as it provides payers and governments with better insights how to spend the available resources in the most efficient way. Further research examining the cost-effectiveness of health promotion targeting physical activity and healthy eating in individuals with mental disorders is required. PMID- 25134637 TI - Analysis of leucocyte antibodies, cytokines, lysophospholipids and cell microparticles in blood components implicated in post-transfusion reactions with dyspnoea. AB - BACKGROUND AND OBJECTIVES: Post-transfusion reactions with dyspnoea (PTR) are major causes of morbidity and death after blood transfusion. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are most dangerous, while transfusion-associated dyspnoea (TAD) is a milder respiratory distress. We investigated blood components for immune and non-immune factors implicated in PTR. MATERIAL AND METHODS: We analysed 464 blood components (RBCs, PLTs, L-PLTs, FFP) transfused to 271 patients with PTR. Blood components were evaluated for 1/antileucocyte antibodies, 2/cytokines: IL-1beta, IL-6, IL-8, TNF-alpha, sCD40L, 3/lysophosphatidylcholines (LysoPCs), 4/microparticles (MPs) shed from plateletes (PMPs), erythrocytes (EMPs) and leucocytes (LMPs). RESULTS: Anti-HLA class I/II antibodies or granulocyte-reactive anti-HLA antibodies were detected in 18.2% of blood components (RBC and FFP) transfused to TRALI and in 0.5% of FFP transfused to TAD cases. Cytokines and LysoPCs concentrations in blood components transfused to PTR patients did not exceed those in blood components transfused to patients with no PTR. Only EMPs percentage in RBCs transfused to patients with TRALI was significantly higher (P < 0.05) than in RBCs transfused to patients with no PTR. CONCLUSION: Immune character of PTR was confirmed mainly in 1/5 TRALI cases. Among non-immune factors, only MPs released from stored RBCs are suggested as potential mediators of TRALI. Our results require further observations in a more numerous and better defined group of patients. PMID- 25134638 TI - Organisation, practice and experiences of mouth hygiene in stroke unit care: a mixed-methods study. AB - AIMS AND OBJECTIVES: To (1) investigate the organisation, provision and practice of oral care in typical UK stroke units; (2) explore stroke survivors', carers' and healthcare professionals' experiences and perceptions about the barriers and facilitators to receiving and undertaking oral care in stroke units. BACKGROUND: Cerebrovascular disease and oral health are major global health concerns. Little is known about the provision, challenges and practice of oral care in the stroke unit setting, and there are currently no evidence-based practice guidelines. DESIGN: Cross-sectional survey of 11 stroke units across Greater Manchester and descriptive qualitative study using focus groups and semi-structured interviews. METHODS: A self-report questionnaire was used to survey 11 stroke units in Greater Manchester. Data were then collected through two focus groups (n = 10) with healthcare professionals and five semi-structured interviews with stroke survivors and carers. Focus group and interview data were recorded, transcribed verbatim and analysed using framework approach. RESULTS: Eleven stroke units in Greater Manchester responded to the survey. Stroke survivors and carers identified a lack of oral care practice and enablement by healthcare professionals. Healthcare professionals identified a lack of formal training to conduct oral care for stroke patients, inconsistency in the delivery of oral care and no set protocols or use of formal oral assessment tools. CONCLUSION: Oral care post-stroke could be improved by increasing healthcare professionals' awareness, understanding and knowledge of the potential health benefits of oral care post-stroke. Further research is required to develop and evaluate the provision of oral care in stroke care to inform evidence-based education and practice. RELEVANCE TO CLINICAL PRACTICE: Development of staff training and education, and evidence-based oral care protocols may potentially benefit patient care and outcomes and be implemented widely across stroke care. PMID- 25134639 TI - Sleepiness induced by sleep-debt enhanced amygdala activity for subliminal signals of fear. AB - BACKGROUND: Emotional information is frequently processed below the level of consciousness, where subcortical regions of the brain are thought to play an important role. In the absence of conscious visual experience, patients with visual cortex damage discriminate the valence of emotional expression. Even in healthy individuals, a subliminal mechanism can be utilized to compensate for a functional decline in visual cognition of various causes such as strong sleepiness. In this study, sleep deprivation was simulated in healthy individuals to investigate functional alterations in the subliminal processing of emotional information caused by reduced conscious visual cognition and attention due to an increase in subjective sleepiness. Fourteen healthy adult men participated in a within-subject crossover study consisting of a 5-day session of sleep debt (SD, 4 h sleep) and a 5-day session of sleep control (SC, 8-h sleep). On the last day of each session, participants performed an emotional face-viewing task that included backward masking of nonconscious presentations during magnetic resonance scanning. RESULTS: Finally, data from eleven participants who were unaware of nonconscious face presentations were analyzed. In fear contrasts, subjective sleepiness was significantly positively correlated with activity in the amygdala, ventromedial prefrontal cortex, hippocampus, and insular cortex, and was significantly negatively correlated with the secondary and tertiary visual areas and the fusiform face area. In fear-neutral contrasts, subjective sleepiness was significantly positively correlated with activity of the bilateral amygdala. Further, changes in subjective sleepiness (the difference between the SC and SD sessions) were correlated with both changes in amygdala activity and functional connectivity between the amygdala and superior colliculus in response to subliminal fearful faces. CONCLUSION: Sleepiness induced functional decline in the brain areas involved in conscious visual cognition of facial expressions, but also enhanced subliminal emotional processing via superior colliculus as represented by activity in the amygdala. These findings suggest that an evolutionally old and auxiliary subliminal hazard perception system is activated as a compensatory mechanism when conscious visual cognition is impaired. In addition, enhancement of subliminal emotional processing might cause involuntary emotional instability during sleep debt through changes in emotional response to or emotional evaluation of external stimuli. PMID- 25134641 TI - Participant Variation by Delivery Site Type in an Evidence-Based Physical Activity Program. AB - This study examined participant demographic and physical function characteristics from EnhanceFitness, an evidence-based physical activity program for older adults. The sample consisted of 19,964 older adults. Participant data included self-reported health and demographic variables, and results for three physical function tests: chair stand, arm curls, and timed up-and-go. Linear regression models compared physical function test results among eight program site types. Participants were, on average, 72 years old, predominantly female, and reported having one chronic condition. Residential site participants' physical function test results were significantly poorer on chair stand and timed up-and-go measures at baseline, and timed up-and-go at a four-month follow-up compared with the reference group (senior centers) after controlling for demographic variables and site clustering. Evidence-based health-promotion programs offered in community settings should assess demographic, health, and physical function characteristics to best serve participants' specific needs, and offer classes tailored to participant function and ability while maintaining program fidelity. PMID- 25134642 TI - Route of delivery linked with subsequent childbirth? PMID- 25134643 TI - Do variations in paraspinal muscle morphology and composition predict low back pain in men? AB - This longitudinal study aimed to clarify the longstanding controversy over whether variations in paraspinal muscle morphology (e.g., size, composition and asymmetry) are predictors of low back pain (LBP). A sample of 99 Finnish men were included in this population-based longitudinal study. Data were collected through a structured interview, physical examination and magnetic resonance imaging (MRI). Baseline measurements of the lumbar multifidus and erector spinae muscles were obtained from T2-weighted axial images at L3-L4 and L5-S1, and interview data were obtained at baseline, 1- and 15-year follow-ups. Few of the paraspinal muscle parameters investigated were predictors of change in LBP frequency, intensity or sciatica at 1- and 15-year follow-ups in the population-based sample, and findings were not consistent across muscles and spinal levels. However, greater multifidus and erector spinae fatty infiltration at L5-S1 was associated with a higher risk of having continued, frequent, persistent LBP at 1 year follow-up. None of the relationships observed was confounded by body mass index or the amount of physical activity at work or leisure. This longitudinal study provided evidence that variations in paraspinal muscle morphology on MRI have a limited, if not uncertain, role in the short- and long-term predictions of LBP in men. PMID- 25134644 TI - Mycobacterium bovis meningitis in young Nigerian-born male. AB - In Denmark, tuberculous meningitis is rare. Central nervous system (CNS) involvement with Mycobacterium bovis is even rarer and has only been seen three times since 1992. We present a case of M. bovis meningitis in a previously healthy young Nigerian-born male, who had been exposed to unpasteurized dairy products in Nigeria but had no known contact with larger mammals. Before the development of meningitis, the patient had several contacts with the health system due to fever and non-specific symptoms. Finally, upon hospital admission, the patient was diagnosed with M. tuberculosis complex meningitis and treated empirically. After 13 days he was discharged without neurological sequelae. Later, the culture revealed M. bovis and treatment was adjusted accordingly. PMID- 25134645 TI - Weekly chlorhexidine douche: does it reduce healthcare-associated bloodstream infections? AB - BACKGROUND: Daily chlorhexidine (CHG) bathing has been used as a precaution to reduce the rate of healthcare-associated bloodstream infections (HA-BSI). The application frequency of CHG bathing remains unclear, this procedure has been implemented daily by this time. The aim of this study was to determine the efficacy of weekly whole-body douche with CHG shower gel on rates of HA-BSI. METHODS: We conducted a prospective intervention trial in medical, surgical, and anesthesiology intensive care units (ICUs) in a tertiary teaching hospital from June 2011 to November 2012. This study included three periods. During the first period, patients received a daily bed bath by wiping with water and soap. In the second period patients were given a weekly douche with water and soap; in the third period patients were given a weekly douche with CHG shower gel. The rates of HA-BSI were compared between the three periods using Poisson regression analysis. RESULTS: The central line-associated bloodstream infection rates did not decline significantly between periods (p = 0.76). The laboratory-confirmed bloodstream infection (LCBSI) rates in the first, second, and third periods were 7.1, 4, and 1.7, respectively. The LCBSI rates were reduced 43.7% from the first period to the second period (p = 0.03). In addition, there was a 57.5% reduction in LCBSI rates between the second and third periods (p < 0.001). Interestingly, the major decline (76.1%) was determined from the first to the third period (p < 0.002). CONCLUSIONS: Weekly douche with CHG shower gel significantly reduced LCBSI rates. Further studies are needed to validate the clinical impact of different intervals of CHG bathing. PMID- 25134646 TI - Impact of hepcidin antimicrobial peptide on iron overload in tuberculosis patients. AB - BACKGROUND: Iron acquisition is essential for the growth of Mycobacterium tuberculosis. Hepcidin is known as an antimicrobial peptide and a component of the innate immune response. Hepcidin inhibits M. tuberculosis growth in vitro. In this study, we decided to identify -582A> G variants of the HAMP promoter in patients with tuberculosis (TB) and investigate its effect on serum iron, ferritin, and hepcidin levels. METHODS: The sample population consisted of 105 patients with TB and 104 healthy individuals. The -582A> G polymorphism was genotyped using a tetra-primers PCR set. Serum levels of hepcidin were determined using an ELISA kit. Statistical analysis was performed using SPSS software. RESULTS: The G allele is meaningfully associated with TB disease (95% confidence interval = 2-4.8, p < 0.000). Significant differences were seen in the levels of serum iron and hepcidin but not ferritin between the -582A>G polymorphism genotypes. There was significant reverse correlation between hepcidin and iron (r = -0.849, p = 0.006). CONCLUSION: A high association was found between serum hepcidin levels and the HAMP -582A> G variants in patients with TB. These observations indicate a hypothetical role of this polymorphism in iron metabolism. Hepcidin could perhaps be an option for the treatment of TB. PMID- 25134647 TI - High vancomycin minimum inhibitory concentration is associated with poor outcome in patients with methicillin-susceptible Staphylococcus aureus bacteremia regardless of treatment. AB - We retrospectively investigated the impact of high vancomycin minimum inhibitory concentration (MIC > 2 MUg/ml) on the outcome of 53 patients with bacteremia caused by methicillin-susceptible Staphylococcus aureus (MSSA). Vancomycin MIC was determined by broth microdilution according to CLSI methods. The primary outcome was 30-day all-cause mortality from the date of the first positive blood culture. The mortality rate was 22.6% (12 of 53 patients). High vancomycin MIC (odds ratio (OR) = 9.3; 95% confidence interval (95% CI) = 1.31-63.20; p = 0.027), Charlson comorbidity index >= 3 (OR = 10.3; 95% CI = 1.3-102.04; p = 0.03), advanced age (OR = 35.8; 95% CI = 2.3-659.2; p = 0.01), and severe sepsis (OR = 8.5; 95% CI = 1.2-61.4; p = 0.03) were associated with mortality. PMID- 25134648 TI - Clinical presentations and outcomes of influenza infection among hematology/oncology patients from a single cancer center: pandemic and post pandemic seasons. AB - BACKGROUND: Influenza can cause severe infection in hematology/oncology patients. The occurrence of the 2009 pandemic represented an opportunity to study the impact of influenza on such patients in pandemic and post-pandemic seasons. METHODS: We retrospectively reviewed medical records of hematology/oncology patients who had laboratory-confirmed influenza infection during the 2009 pandemic and the first post-pandemic seasons. We assessed influenza-related outcomes in both seasons with emphasis on the development of pneumonia and mortality. We also analyzed factors associated with poor outcomes. RESULTS: We included 350 patients; 207 were diagnosed in the pandemic and 143 in the post pandemic seasons. Influenza severity was similar in both seasons with no significant differences in the development of pneumonia or death. Infection with the pH1N1 virus was associated with the development of pneumonia (24.7% vs 14.9%, p = 0.029) but did not affect mortality. A multivariate analysis showed that initiation of antiviral treatment after > 48 h, healthcare acquisition of influenza, and low albumin were independent risk factors for the development of pneumonia (p values 0.022, 0.003, and < 0.0001, respectively). A log-rank test showed increased mortality in patients who received therapy > 48 h after onset of symptoms (p = 0.001). CONCLUSIONS: In hematology/oncology patients, influenza was as severe in the post-pandemic as in the pandemic season. Pneumonia developed more commonly in patients infected with pH1N1 virus. Healthcare acquisition of infection and low albumin were associated with the development of pneumonia. Delayed initiation of antiviral treatment was associated with both pneumonia and mortality. PMID- 25134649 TI - Usefulness of PCR-RFLP coa gene for clonal classification of methicillin resistant Staphylococcus aureus isolates in tertiary hospitals. AB - One hundred and one methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates were classified into 10 genotypes based on their polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) coa pattern. PCR RFLP coa patterns correlated with the clonal complex (CC) with the exception of CC5, which was related to 2 patterns (B and E). The PCR-RFLP coa gene technique provides a useful preliminary method to monitor variations in MRSA populations. PMID- 25134651 TI - Misdiagnosed amoebiasis leading to liver abscess. PMID- 25134650 TI - Cluster of linezolid-resistant Enterococcus faecium ST117 in Norwegian hospitals. AB - A linezolid-resistant, vancomycin-susceptible Enterococcus faecium strain was isolated from 3 patients who had not received linezolid. The first patient was hospitalized in the same hospitals and wards as the 2 following patients. The E. faecium isolates were resistant to linezolid (minimum inhibitory concentration 8 32 mg/l), ampicillin, and high levels of gentamicin. Resistance to linezolid was associated with a G2576T mutation in 23S rDNA. The cfr linezolid resistance gene was not detected. The 3 isolates showed identical DNA fingerprints by pulsed field gel electrophoresis, belonged to ST117, and harboured virulence genes esp, hyl, acm, efaAfm, srgA, ecbA, scm, pilA, pilB, and pstD typically associated with high-risk E. faecium genotypes. The linezolid-resistant E. faecium high-risk clone caused bacteraemia in the first 2 cancer patients and survived in the hospital environment for more than a year before appearing in the urethral catheter of the third patient. PMID- 25134652 TI - Mycobacterium abscessus: a rare cause of vascular graft infection. AB - Prosthetic vascular graft infection (PVGI) following vascular reconstructive surgery is an uncommon but serious complication and is associated with high morbidity as well as mortality rate. Staphylococcal species are the most common organisms causing PVGI. Mycobacterium abscessus is a very rare cause of PVGI and poses a significant diagnostic and management dilemma. To the best of our knowledge, we report the third documented case of M. abscessus vascular graft infection that was diagnosed with 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan and treated successfully. PMID- 25134653 TI - Acute fulminant hepatitis E virus genotype 3e infection: description of the first case in Europe. AB - Hepatitis E virus (HEV) is the most important causative agent of acute hepatitis in developing countries. The disease is usually characterized by a self-limiting, benign course. However, when particular conditions coexist (pregnancy, old age, pre-existing liver disease) it may run an unfavourable course. To date, 4 HEV genotypes have been described. Historically, in the Western world, HEV infection was considered a travel-related disease, however in the last 2 decades a great number of non-travel-related autochthonous cases have been described, more often related to genotype 3 or 4 and in the context of zoonosis. We report the case of an elderly Italian man with an acute fulminant HEV infection genotype 3e that developed in the context of pre-existing liver disease; this is the first case of an unfavourable outcome associated with subgenotype 3e. The potential pathogenicity of this subgenotype together with the influence of host-related risk factors are discussed. PMID- 25134654 TI - Testing for hepatitis B virus and HIV in patients with chronic hepatitis C: screening performance and outcome. AB - BACKGROUND: Patients infected with hepatitis C virus (HCV) and co-infected with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) are at increased risk for progression of liver disease. The aim of this study was to assess HBV and HIV screening performance and outcome in HCV patients followed at a Danish university hospital and affiliated regional outpatient clinics. METHODS: HBV and HIV serology data were extracted from a quality assurance database for the assessment of screening performance in patients diagnosed with chronic HCV infection during the period 1 January 1996 to 31 December 2011. Patients with incomplete and missing serology data had complementary serology tests performed to assess the prevalence of HBV and HIV co-infection and HBV immune status. RESULTS: Among 624 HCV patients, 10 (2%) were co-infected with chronic HBV and 32 (5%) with HIV. Approximately half of the cohort were non-immune to HBV or had an unknown HBV serology status. Serology results consistent with resolved infection and HBV vaccination were found in 209 (33%) and 65 (10%) patients, respectively. During the 16-y observation period, HBV and HIV screening coverage at HCV diagnosis increased from 23% to 92% and from 38% to 80%, respectively. CONCLUSION: Despite improvements throughout the study period, HBV and HIV serology screening remained incomplete. The majority of patients were either HBV non-immune or had an unknown HBV serology status. These findings thus call for a more proactive screening approach as well as an improved HBV vaccination strategy for patients with chronic HCV infection. PMID- 25134640 TI - DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD. METHODS: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <0.7 and FEV1 < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLCCT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLCCT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis. RESULTS: Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, beta = 0.42L, P = 4.66 * 10-8). CONCLUSIONS: In COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD. PMID- 25134655 TI - A method for lipid droplet isolation from human placenta for further analyses in clinical trials. AB - We describe a method to isolate lipids droplets from human placental tissue for future lipid analyses. We collected placentas at term from healthy women (n=5) and tested three methods published for lipids droplets isolation in other tissues. Only one of the methods, when modified, isolated lipids droplets from placental tissue, whereas all three methods allowed lipids droplets isolation from rat liver (control tissue) and separation of lipids droplets from blood contamination of the tissue. The placental lipids droplets layer was characterized by the presence of adipophilin while no N+ /K+-ATPase as plasma membrane contamination was detected. Intraplacental triglyceride content showed a high coefficient of variation (~42%), whereas for cholesterol and phospholipids this was lower. One method was effective for isolation of placental lipids droplets. It is necessary to collect a pool of placental tissue pieces for placental lipids droplets analyses. Freezing in liquid nitrogen is recommended. PMID- 25134657 TI - Graphitic carbon nitride nanosheets: one-step, high-yield synthesis and application for Cu2+ detection. AB - In this article we report on the one-step, rapid, high-yield synthesis of graphitic carbon nitride (g-C3N4) nanosheets for the first time. The nanosheets were obtained by pyrolyzing a melamine-KBH4 mixture under Ar. As a fluorosensor for Cu(2+), the g-C3N4 nanosheets exhibit a detection limit as low as 0.5 nM and high selectivity in buffer solutions, and this sensor was applied to the analysis of lake water samples. The electrogenerated chemiluminescence (ECL) behavior of the g-C3N4 nanosheets using Na2S2O8 as the coreactant was also studied. Results suggest that the ECL intensity of the g-C3N4 nanosheets was linear over concentrations of 0-45 nM, with a detection limit of 1.2 nM for Cu(2+). PMID- 25134659 TI - The omega-3 fatty acid docosahexaenoic acid favorably modulates the inflammatory pathways and macrophage polarization within aorta of LDLR(-/-) mice. AB - The omega-3 fatty acid docosahexaenoic acid (DHA) has potent anti-atherogenic properties but its mechanisms of action at the vascular level remain poorly explored. Knowing the broad range of molecular targets of omega-3 fatty acids, microarray analysis was used to open-mindedly evaluate the effects of DHA on aorta gene expression in LDLR(-/-) mice and better understand its local anti atherogenic action. Mice were fed an atherogenic diet and received daily oral gavages with oils rich in oleic acid or DHA. Bioinformatics analysis of microarray data first identified inflammation and innate immunity as processes the most affected by DHA supplementation within aorta. More precisely, several down-regulated genes were associated with the inflammatory functions of macrophages (e.g., CCL5 and CCR7), cell movement (e.g., ICAM-2, SELP, and PECAM 1), and the major histocompatibility complex (e.g., HLA-DQA1 and HLA-DRB1). Interestingly, several genes were identified as specific biomarkers of macrophage polarization, and their changes suggested a preferential orientation toward a M2 reparative phenotype. This observation was supported by the upstream regulator analysis highlighting the involvement of three main regulators of macrophage polarization, namely PPARgamma (z-score = 2.367, p = 1.50 * 10(-13)), INFgamma (z score = -2.797, p = 2.81 * 10(-14)), and NFkappaB (z-score = 2.360, p = 6.32 * 10(-9)). Moreover, immunohistological analysis of aortic root revealed an increased abundance of Arg1 (+111 %, p = 0.01), a specific biomarker of M2 macrophage. The present study showed for the first time that DHA supplementation during atherogenesis is associated with protective modulation of inflammation and innate immunity pathways within aorta putatively through the orientation of plaque macrophages toward a M2 reparative phenotype. PMID- 25134658 TI - Content validity of the Comprehensive ICF Core Set for multiple sclerosis from the perspective of speech and language therapists. AB - BACKGROUND: The Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for Multiple Sclerosis (MS) is a comprehensive framework to structure the information obtained in multidisciplinary clinical settings according to the biopsychosocial perspective of the International Classification of Functioning, Disability and Health (ICF) and to guide the treatment and rehabilitation process accordingly. It is now undergoing validation from the user perspective for which it has been developed in the first place. AIMS: To validate the content of the Comprehensive ICF Core Set for MS from the perspective of speech and language therapists (SLTs) involved in the treatment of persons with MS (PwMS). METHODS & PROCEDURES: Within a three round e-mail-based Delphi Study 34 SLTs were asked about PwMS' problems, resources and aspects of the environment treated by SLTs. Responses were linked to ICF categories. Identified ICF categories were compared with those included in the Comprehensive ICF Core Set for MS to examine its content validity. OUTCOMES & RESULTS: Thirty-four SLTs named 524 problems and resources, as well as aspects of environment. Statements were linked to 129 ICF categories (60 Body-functions categories, two Body-structures categories, 42 Activities-&-participation categories, and 25 Environmental-factors categories). SLTs confirmed 46 categories in the Comprehensive ICF Core Set. Twenty-one ICF categories were identified as not-yet-included categories. CONCLUSIONS & IMPLICATIONS: This study contributes to the content validity of the Comprehensive ICF Core Set for MS from the perspective of SLTs. Study participants agreed on a few not-yet-included categories that should be further discussed for inclusion in a revised version of the Comprehensive ICF Core Set to strengthen SLTs' perspective in PwMS' neurorehabilitation. PMID- 25134660 TI - Treatment of Cushing's disease: a mechanistic update. AB - Cushing's disease (CD) is characterized by an ACTH-producing anterior corticotrope pituitary adenoma. If hypothalamus-pituitary-adrenal (HPA) axis physiology is disrupted, ACTH secretion increases, which in turn stimulates adrenocortical steroidogenesis and cortisol production. Medical treatment plays an important role for patients with persistent disease after surgery, for those in whom surgery is not feasible, or while awaiting effects of radiation. Multiple drugs, with different mechanisms of action and variable efficacy and tolerability for controlling the deleterious effects of chronic glucocorticoid excess, are available. The molecular basis and clinical data for centrally acting drugs, adrenal steroidogenesis inhibitors, and glucocorticoid receptor antagonists are reviewed, as are potential novel molecules and future possible targets for CD treatment. Although progress has been made in the understanding of specific corticotrope adenoma receptor physiology and recent clinical studies have detected improved effects with a combined medical therapy approach, there is a clear need for a more efficacious and better-tolerated medical therapy for patients with CD. A better understanding of the molecular mechanisms in CD and of HPA axis physiology should advance the development of new drugs in the future. PMID- 25134661 TI - Interfacial stability and shape change of anisotropic endoskeleton droplets. AB - The delivery of suspended active ingredients to a surface is a central function of numerous commercial cosmetic, drug, and agricultural formulations. Many products use liquid droplets as a delivery vehicle but, because interfacial tension keeps droplets spherical, these materials cannot exploit the benefits of anisotropic shape and shape change offered by solid colloids. In this work, individual droplet manipulation is used to produce viscoelastic droplets that can stably retain non-spherical shapes by balancing the Laplace pressure of the liquid-liquid interface with the elasticity of an internal crystalline network. A stability criterion is developed for idealized spherocylindrical droplets and shown to agree with experimental data for varying droplet size and rheology. Shape change can be induced in the anisotropic droplets by upsetting the balance of droplet interfacial tension and internal rheology. Using dilution to increase the interfacial tension shows that external stimuli can trigger collapse and shape change in these droplets. The droplets wrap around substrates during collapse, improving contact and adhesion. The model is used to develop design criteria for production of droplets with tunable response. PMID- 25134662 TI - Emergency transcatheter arterial embolization for massive hemoptysis due to pulmonary tuberculosis and tuberculosis sequelae. AB - To explore the strategy and curative effect of emergency transcatheter arterial embolization (ETAE) in patients with massive hemoptysis due to pulmonary tuberculosis and tuberculosis sequelae. A total of 148 patients with massive hemoptysis due to pulmonary tuberculosis underwent emergency arteriography. After the bleeding artery was located, patients were given embolotherapy using gelfoam strips, coils, and polyvinyl alcohol particles. The arteriography manifestations and therapeutic outcomes in all patients were retrospectively analyzed. ETAE was performed successfully in 143 patients after location of the bleeding arteries. The bleeding arteries could not be located in another five patients, and embolotherapy, therefore, could not be performed. Among these five patients, three underwent surgical resection and two died of complications of tuberculosis/fungal ball coinfection. During a 2-year follow-up period, there were 15 cases of recurrent hemoptysis after initial embolotherapy. Among these, four cases were resolved by re-embolization, 11 patients still had massive hemoptysis after re-embolization who underwent surgical resection and resolved the hemoptysis eventually. Successful hemostasis was achieved by ETAE in 132 patients (89.19%; 132/148). No severe complications occurred after embolotherapy. ETAE is a safe and effective treatment for massive hemoptysis due to pulmonary tuberculosis. The key to successful treatment is thorough and complete embolization of the bleeding arteries. In the event of failure of embolotherapy, surgical resection should be used to resolve the bleeding. PMID- 25134664 TI - Low-temperature reduction of brownmillerite CaFeO2.5 in LaAlO3/CaFeO2.5 heterostructures made on SrTiO3. AB - When LaAlO3/CaFeO2.5 thin-film heterostructures made on SrTiO3 were annealed with CaH2 at low temperatures below 300 degrees C, the brownmillerite CaFeO2.5 layer was reduced to CaFeO2 with an infinite-layer structure while both the LaAlO3 capping layer and the SrTiO3 substrate remained intact. The reduction behaviour strongly depends on the lattice matching of LaAlO3 to CaFeO2.5, suggesting that oxygen ions migrate through the coherently grown LaAlO3 layer of the heterostructure predominantly in the out-of-plane direction. The structural defects near the interface in the relaxed-structure LaAlO3 capping layer prevent the oxygen ions from migrating. PMID- 25134663 TI - Knockdown of Akt2 expression by shRNA inhibits proliferation, enhances apoptosis, and increases chemosensitivity to paclitaxel in human colorectal cancer cells. AB - Akt2 overexpression correlates with chemoresistance of colorectal cancer (CRC). However, the cellular functions and precise signals elicited by Akt2 in LSCC have not been elucidated. Here, we transfected a CRC cell line HCT116 with Akt-2 targeted shRNA in order to establish a cell line with Akt2 knockdown. In vitro experiments showed that knockdown Akt2 in HCT116 cells was associated with decrease in cell proliferation as well as enhanced cell apoptosis. Furthermore, our results demonstrated that Akt2 knockdown correlated with elevated chemosensitivity of HCT116 cells to paclitaxel. Importantly, we found that knockdown of AKt2 resulted in downregulation of MDR-1 and MRP-1. Our findings may lead to a better understanding of the biological effect of Akt2 and may provide mechanistic insights for developing potential therapeutic strategies targeting AKt2. PMID- 25134665 TI - The relationship between promotions committees' identification of problem medical students and subsequent state medical board actions. AB - Studies have found unprofessional behavior in medical school was associated with disciplinary action by state medical boards. For medical schools, promotions committees are responsible for identifying which students do not demonstrate academic performance and professional behavior acceptable for promotion and graduation. The objective of this study was to determine if student identification by promotions committees during medical school was associated with disciplinary actions by state medical boards later in practice. We reviewed 20 years of promotions committees' records from a single institution and noted students identified by promotions committees for performance or behavioral issues. These were compared with disciplinary action reports from the Federation of State Medical Boards (FSMB) for graduates. Over the two decades, 2,131 students matriculated and 2,078 of these graduated. The promotions committees identified 140 students for poor academic performance or behavioral problems (140/2,078, 6.7 %). Of these, 108 students graduated. FSMB records showed 29 of the 2,078 graduates had sanctions by state boards (29/2,078, 1.4 %). Only four students that had actions by state medical boards were among the 108 graduated students identified by medical school promotions committees (4/108, 3.7 %). Of the students not identified by promotions committees, 25 eventually had disciplinary actions (25/1,970, 1.3 %). The odds of having state medical board action if identified by promotions committees was 3.0 (CI 1.02-8.8, p < 0.05). In conclusion, identification of students by medical school promotions committees was later associated with state medical board actions. However, most graduates with state medical board actions were not identified by medical school promotions committees. PMID- 25134666 TI - Cost in medical education: one hundred and twenty years ago. AB - The first full paper that is dedicated to cost in medical education appears in the BMJ in 1893. This paper "The cost of a medical education" outlines the likely costs associated with undergraduate education at the end of the nineteenth century, and offers guidance to the student on how to make financial planning. Many lessons can be gleaned from the paper about the cost and other aspects of nineteenth century medical education. Cost is viewed almost exclusively from the domain of the male gender. Cost is viewed not just from the perspective of a young man but of a young gentleman. There is a strong implication that medicine is a club and that you have to have money to join the club and then to take part in the club's activities. Cost affects choice of medical school and selection into schools. The paper places great emphasis on the importance of passing exams at their first sitting and progressing through each year in a timely manner mainly to save costs. The subject of cost is viewed from the perspective of the payer-at this time students and their families. The paper encourages the reader to reflect on what has and has not changed in this field since 1893. Modern medical education is still expensive; its expense deters students; and we have only started to think about how to control costs or how to ensure value. Too much of the cost of medical education continues to burden students and their families. PMID- 25134667 TI - Estimating a DIF decomposition model using a random-weights linear logistic test model approach. AB - A differential item functioning (DIF) decomposition model separates a testlet item DIF into two sources: item-specific differential functioning and testlet specific differential functioning. This article provides an alternative model building framework and estimation approach for a DIF decomposition model that was proposed by Beretvas and Walker (2012). Although their model is formulated under multilevel modeling with the restricted pseudolikelihood estimation method, our approach illustrates DIF decomposition modeling that is directly built upon the random-weights linear logistic test model framework with the marginal maximum likelihood estimation method. In addition to demonstrating our approach's performance, we provide detailed information on how to implement this new DIF decomposition model using an item response theory software program; using DIF decomposition may be challenging for practitioners, yet practical information on how to implement it has previously been unavailable in the measurement literature. PMID- 25134668 TI - Chinese English Learners' Strategic Competence. AB - The present study aims to investigate Chinese English learners' ability to use communication strategies (CSs). The subjects are put in a relatively real English referential communication setting and the analyses of the research data show that Chinese English learners, when encountering problems in foreign language (FL) communication, are characterized by the frequent use of substitution, approximation, circumlocution, literal translation, exemplification, word coinage, repetition, and the infrequent use of cultural-knowledge and paralinguistic CSs. The rare use of paralinguistic strategies is found to be typical of Chinese English learners. The high frequency of literal translation, one first language (L1)-based strategy in our study sample, suggests that FL learners' use of L1-based CSs may depend more upon the developmental stage of their target language than the typology distance between L1 and the target language. The frequency of repetition reveals one fact that the Chinese English learners lack variety and flexibility in their use of CSs. Based on these findings, it was indicated that learners' use of CSs is influenced by a variety of factors, among which the development stage of their interlanguage and their cultural background are identified as two important factors. Some implications are finally suggested for the English foreign language teaching practice in China. PMID- 25134669 TI - 18F-FDG PET of the hands with a dedicated high-resolution PEM system (arthro PET): correlation with PET/CT, radiography and clinical parameters. AB - PURPOSE: The aim of this study was to prospectively determine the feasibility and compare the novel use of a positron emission mammography (PEM) scanner with standard PET/CT for evaluating hand osteoarthritis (OA) with (18)F-FDG. METHODS: Institutional review board approval and written informed consent were obtained for this HIPAA-compliant prospective study in which 14 adults referred for oncological (18)F-FDG PET/CT underwent dedicated hand PET/CT followed by arthro PET using the PEM device. Hand radiographs were obtained and scored for the presence and severity of OA. Summed qualitative and quantitative joint glycolytic scores for each modality were compared with the findings on plain radiography and clinical features. RESULTS: Eight patients with clinical and/or radiographic evidence of OA comprised the OA group (mean age 73 +/- 7.7 years). Six patients served as the control group (53.7 +/- 9.3 years). Arthro-PET quantitative and qualitative joint glycolytic scores were highly correlated with PET/CT findings in the OA patients (r = 0.86. p = 0.007; r = 0.94, p = 0.001). Qualitative arthro PET and PET/CT joint scores were significantly higher in the OA patients than in controls (38.7 +/- 6.6 vs. 32.2 +/- 0.4, p = 0.02; 37.5 +/- 5.4 vs. 32.2 +/- 0.4, p = 0.03, respectively). Quantitative arthro-PET and PET/CT maximum SUV-lean joint scores were higher in the OA patients, although they did not reach statistical significance (20.8 +/- 4.2 vs. 18 +/- 1.8, p = 0.13; 22.8 +/- 5.38 vs. 20.1 +/- 1.54, p = 0.21). By definition, OA patients had higher radiographic joint scores than controls (30.9 +/- 31.3 vs. 0, p = 0.03). CONCLUSION: Hand imaging using a small field of view PEM system (arthro-PET) with FDG is feasible, performing comparably to PET/CT in assessing metabolic joint activity. Arthro-PET and PET/CT showed higher joint FDG uptake in OA. Further exploration of arthro PET in arthritis management is warranted. PMID- 25134670 TI - (68)Ga-DOTATOC PET/CT provides accurate tumour extent in patients with extraadrenal paraganglioma compared to (123)I-MIBG SPECT/CT. AB - PURPOSE: The aim of this study was to compare the accuracy of (123)I-MIBG SPECT/CT with that of (68)Ga-DOTATOC PET/CT for staging extraadrenal paragangliomas (PGL) using both functional and anatomical images (i.e. combined cross-sectional imaging) as the reference standards. METHODS: The study included three men and seven women (age range 26 to 73 years) with anatomical and/or histologically proven disease. Three patients had either metastatic head and neck PGL (HNPGL) or multifocal extraadrenal PGL, and seven patients had nonmetastatic extraadrenal disease. Comparative evaluation included morphological imaging with CT, functional imaging with (68)Ga-DOTATOC PET, and (123)I-MIBG imaging. The imaging results were analysed on a per-patient and on a per-lesion basis. RESULTS: On a per-patient basis, the detection rate of (68)Ga-DOTATOC PET was 100 %, whereas that of planar (123)I-MIBG imaging was 10.0 % and with SPECT/CT 20.0 % for both nonmetastatic and metastatic/multifocal extraadrenal PGL. On a per lesion basis, the overall sensitivity of (68)Ga-DOTATOC PET was 100 % (McNemar p < 0.5), that of planar (123)I-MIBG imaging was 3.4 % (McNemar p < 0.001) and that of SPECT/CT was 6.9 % (McNemar p < 0.001). Both (68)Ga-DOTATOC PET and anatomical imaging identified 27 lesions. Planar (123)I-MIBG imaging identified only one lesion, and SPECT/CT two lesions. Two additional lesions were detected by (68)Ga DOTATOC PET but not by either (123)I-MIBG or CT imaging. CONCLUSION: Our analysis in this patient cohort indicated that (68)Ga-DOTATOC PET/CT is superior to (123)I MIBG SPECT/CT, particularly in head and neck and bone lesions, and provides valuable information for staging extraadrenal PGL, particularly in patients with surgically inoperable tumours or multifocal/malignant disease. PMID- 25134673 TI - Quantitative proteomics reveals the kinetics of trypsin-catalyzed protein digestion. AB - Trypsin is the popular protease to digest proteins into peptides in shotgun proteomics, but few studies have attempted to systematically investigate the kinetics of trypsin-catalyzed protein digestion in proteome samples. In this study, we applied quantitative proteomics via triplex stable isotope dimethyl labeling to investigate the kinetics of trypsin-catalyzed cleavage. It was found that trypsin cleaves the C-terminal to lysine (K) and arginine (R) residues with higher rates for R. And the cleavage sites surrounded by neutral residues could be quickly cut, while those with neighboring charged residues (D/E/K/R) or proline residue (P) could be slowly cut. In a proteome sample, a huge number of proteins with different physical chemical properties coexists. If any type of protein could be preferably digested, then limited digestion could be applied to reduce the sample complexity. However, we found that protein abundance and other physicochemical properties, such as molecular weight (Mw), grand average of hydropathicity (GRAVY), aliphatic index, and isoelectric point (pI) have no notable correlation with digestion priority of proteins. PMID- 25134674 TI - Emerging concepts and strategies in analytical glow discharges. PMID- 25134672 TI - Belinostat: first global approval. AB - Belinostat [Beleodaq((r)) (US)], a small-molecule hydroxamate-type inhibitor of class I, II and IV histone deacetylase (HDAC) enzymes, has been developed by TopoTarget and Spectrum Pharmaceuticals for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). Belinostat has received its first global approval as monotherapy for this indication in the US, under the Food and Drug Administration's accelerated approval program. This article summarizes the milestones in the development of belinostat leading to this first approval for the treatment of PTCL. PMID- 25134671 TI - Chronic renal insufficiency in heart transplant recipients: risk factors and management options. AB - Renal dysfunction after heart transplantation is a frequently observed complication, in some cases resulting in significant limitation of quality of life and reduced survival. Since the pathophysiology of renal failure (RF) is multifactorial, the current etiologic paradigm for chronic kidney disease after heart transplantation relies on the concept of calcineurin inhibitor (CNI) related nephrotoxicity acting on a predisposed recipient. Until recently, the management of RF has been restricted to the minimization of CNI dosage and general avoidance of classic nephrotoxic risk factors, with somewhat limited success. The recent introduction of proliferation signal inhibitors (PSIs) (sirolimus and everolimus), a new class of immunosuppressive drugs lacking intrinsic nephrotoxicity, has provided a completely new alternative in this clinical setting. As clinical experience with these new drugs increases, new renal-sparing strategies are becoming available. PSIs can be used in combination with reduced doses of CNIs and even in complete CNI-free protocols. Different strategies have been devised, including de novo use to avoid acute renal toxicity in high-risk patients immediately after transplantation, or more delayed introduction in those patients developing chronic RF after prolonged CNI exposure. In this review, the main information on the clinical relevance and pathophysiology of RF after heart transplantation, as well as the currently available experience with renal-sparing immunosuppressive regimens, particularly focused on the use of PSIs, is reviewed and summarized, including the key practical points for their appropriate clinical usage. PMID- 25134675 TI - Can mercury in fish be reduced by water level management? Evaluating the effects of water level fluctuation on mercury accumulation in yellow perch (Perca flavescens). AB - Mercury (Hg) contamination of fisheries is a major concern for resource managers of many temperate lakes. Anthropogenic Hg contamination is largely derived from atmospheric deposition within a lake's watershed, but its incorporation into the food web is facilitated by bacterial activity in sediments. Temporal variation in Hg content of fish (young-of-year yellow perch) in the regulated lakes of the Rainy-Namakan complex (on the border of the United States and Canada) has been linked to water level (WL) fluctuations, presumably through variation in sediment inundation. As a result, Hg contamination of fish has been linked to international regulations of WL fluctuation. Here we assess the relationship between WL fluctuations and fish Hg content using a 10-year dataset covering six lakes. Within-year WL rise did not appear in strongly supported models of fish Hg, but year-to-year variation in maximum water levels (?maxWL) was positively associated with fish Hg content. This WL effect varied in magnitude among lakes: In Crane Lake, a 1 m increase in ?maxWL from the previous year was associated with a 108 ng increase in fish Hg content (per gram wet weight), while the same WL change in Kabetogama was associated with only a 5 ng increase in fish Hg content. In half the lakes sampled here, effect sizes could not be distinguished from zero. Given the persistent and wide-ranging extent of Hg contamination and the large number of regulated waterways, future research is needed to identify the conditions in which WL fluctuations influence fish Hg content. PMID- 25134676 TI - Cytochrome P4501A1 expression in blubber biopsies of endangered false killer whales (Pseudorca crassidens) and nine other odontocete species from Hawai'i. AB - Odontocetes (toothed whales) are considered sentinel species in the marine environment because of their high trophic position, long life spans, and blubber that accumulates lipophilic contaminants. Cytochrome P4501A1 (CYP1A1) is a biomarker of exposure and molecular effects of certain persistent organic pollutants. Immunohistochemistry was used to visualize CYP1A1 expression in blubber biopsies collected by non-lethal sampling methods from 10 species of free ranging Hawaiian odontocetes: short-finned pilot whale, melon-headed whale, pygmy killer whale, common bottlenose dolphin, rough-toothed dolphin, pantropical spotted dolphin, Blainville's beaked whale, Cuvier's beaked whale, sperm whale, and endangered main Hawaiian Islands insular false killer whale. Significantly higher levels of CYP1A1 were observed in false killer whales and rough-toothed dolphins compared to melon-headed whales, and in general, trophic position appears to influence CYP1A1 expression patterns in particular species groups. No significant differences in CYP1A1 were found based on age class or sex across all samples. However, within male false killer whales, juveniles expressed significantly higher levels of CYP1A1 when compared to adults. Total polychlorinated biphenyl (?PCBs) concentrations in 84% of false killer whales exceeded proposed threshold levels for health effects, and ?PCBs correlated with CYP1A1 expression. There was no significant relationship between PCB toxic equivalent quotient and CYP1A1 expression, suggesting that this response may be influenced by agonists other than the dioxin-like PCBs measured in this study. No significant differences were found for CYP1A1 expression among social clusters of false killer whales. This work provides a foundation for future health monitoring of the endangered stock of false killer whales and other Hawaiian odontocetes. PMID- 25134677 TI - Microcalorimetric study of the effects of long-term fertilization on soil microbial activity in a wheat field on the Loess Plateau. AB - The effects of the long-term inorganic (nitrogen, N; phosphate, P) and organic (manure, M; straw, S) fertilizers/managemenet individually and in combinations (N, NP, SNP, M, and MNP) on soil microbial activity were investigated in a wheat field on the Loess Plateau, China. Microcalorimetry was used to determine microbial activity under different treatments. Nearly 30 years of consecutive fertilization has altered the culturable population of soil bacteria and fungi, the highest ones were detected in the treatments of manure and MNP, followed by the NP and SNP treatments. The microbial growth rate constant (MU/h(-1)) was significantly greater in the MNP treatment than all the other treatments. The total heat exchange values (Q/J) were the highest in the MNP and NP treatments, which were significantly different from the N and M treatments. The peak height (P(t)/MUW) were significantly higher in MNP and NP treatments than in the remaining treatments. The peak time values (t(p)/h) among the MNP, NP, SNP and M, N and CK treatments were significantly different. In general, comparing with control, soil microbial activity was much higher in MNP, NP and SNP treatments, all including the phosphate fertilizer. Our results showed that the application of inorganic fertilizer and organic manure have positive effects on multiple soil chemical parameters, soil microorganism abundance and activity, and hence crop yield. PMID- 25134678 TI - Effect of triclosan on reproduction, DNA damage and heat shock protein gene expression of the earthworm Eisenia fetida. AB - Triclosan (TCS) is released into the terrestrial environment via the application of sewage sludge and reclaimed water to agricultural land. More attention has been paid to its effect on non-target soil organisms. In the present study, chronic toxic effects of TCS on earthworms at a wide range of concentrations were investigated. The reproduction, DNA damage, and expression levels of heat shock protein (Hsp70) gene of earthworms were studied as toxicity endpoints. The results showed that the reproduction of earthworms were significantly reduced (p < 0.05) after exposure to the concentrations ranges from 50 to 300 mg kg(-1), with a half-maximal effective concentration (EC50) of 142.11 mg kg(-1). DNA damage, detected by the comet assay, was observed and there was a clear significant (R(2) = 0.941) relationship between TCS concentrations and DNA damage, with the EC50 value of 8.85 mg kg(-1). The expression levels of Hsp70 gene of earthworms were found to be up-regulated under the experimental conditions. The expression level of hsp70 gene increased, up to about 2.28 folds that in the control at 50 mg kg(-1). The EC50 value based on the Hsp70 biomarker was 1.79 mg kg(-1). Thus, among the three toxicity endpoints, the Hsp70 gene was more sensitive to TCS in soil. PMID- 25134679 TI - Long-term effects of fertilizer on soil enzymatic activity of wheat field soil in Loess Plateau, China. AB - The effects of long-term (29 years) fertilization on local agro-ecosystems in the Loess Plateau of northwest China, containing a single or combinations of inorganic (Nitrogen, N; Phosphate, P) and organic (Mature, M Straw, S) fertilizer, including N, NP, SNP, M, MNP, and a control. The soil enzymes, including dehydrogenase, urease, alkaline phosphatase, invertase and glomalin, were investigated in three physiological stages (Jointing, Dough, and Maturity) of wheat growth at three depths of the soil profile (0-15, 16-30, 31-45 cm). We found that the application of farmyard manure and straw produced the highest values of soil enzymatic activity, especially a balanced applied treatment of MNP. Enzymatic activity was lowest in the control. Values were generally highest at dough, followed by the jointing and maturity stages, and declined with soil profile depth. The activities of the enzymes investigated here are significantly correlated with each other and are correlated with soil nutrients, in particular with soil organic carbon. Our results suggest that a balanced application of fertilizer nutrients and organic manure (especially those containing P) has positive effects on multiple soil chemical parameters, which in turn enhances enzyme activity. We emphasize the role of organic manure in maintaining soil organic matter and promoting biological activity, as its application can result in a substantial increase in agricultural production and can be sustainable for many years. PMID- 25134680 TI - Aging of the nitric oxide system: are we as old as our NO? AB - BACKGROUND: Impaired generation and signaling of nitric oxide (NO) contribute substantially to cardiovascular (CV) risk (CVR) associated with hypertension, hyperlipidemia, and diabetes mellitus. In our rapidly aging society, advanced age is, in itself, a consistent and independent CVR factor. Many processes involved in aging are modulated by NO. We therefore postulated that aging might be independently associated with impaired NO signaling. METHODS AND RESULTS: In a prospective cohort study of 204 subjects (mean age 63+/-6 at study entry), we evaluated the effects of 4 years of aging on parameters of NO generation and effect, including platelet aggregability and responsiveness to NO, and plasma concentrations of the NO synthase inhibitor, asymmetric dimethylarginine (ADMA). Clinical history, lipid profile, high-sensitivity C-reactive protein, routine biochemistry, and 25-hydroxyvitamin D levels were obtained at study entry and after 4 years of follow-up. Aging was associated with marked deterioration of responsiveness of platelets to NO (P<0.0001) and increases in plasma ADMA concentrations (P<0.0001). There was a significant correlation between changes in these parameters over time (r=0.2; P=0.013). On multivariable analyses, the independent correlates of deterioration of responsiveness of platelets to NO were female gender (beta=0.17; P=0.034) and low vitamin D concentrations (beta=0.16; P=0.04), whereas increases in ADMA were associated with presence of diabetes (beta=0.16; P=0.03) and impaired renal function (beta=0.2; P=0.004). CONCLUSIONS: Aging is associated with marked impairment of determinants of NO generation and effect, to an extent which is commensurate with adverse impact on CV outcomes. This deterioration represents a potential target for therapeutic interventions. PMID- 25134683 TI - Prefronto-subcortical imbalance characterizes poor decision-making: neurochemical and neural functional evidences in rats. AB - A major challenge of decision-making research in recent years has been to develop models of poor decision-making to identify its neural bases. Toward this goal, we developed a Rat Gambling Task that discerns good and poor decision-makers in a complex and conflicting situation such as the human Iowa Gambling Task. Nothing is known about the role of the monoaminergic modulatory systems in shaping these phenotypes. Moreover, functional and temporal contributions of brain areas during poor compared to good decision-making remains elusive. Good and poor decision makers were identified in the Rat Gambling Task. We investigated neurobiological correlates of decision-making capacities in (1) dopamine and serotonin turnovers using post-mortem tissue measurements, (2) the neural circuits differentially recruited during decision-making within the prefronto-subcortical network using cellular Fos immunodetection. Imbalance in monoamine metabolism was revealed in poor decision-makers, i.e. a higher infralimbic vs. lower amygdala serotonergic metabolism. Moreover, good decision-making recruited a wide prefronto-subcortical network but once good choices had been made, a disengagement of key prefrontal areas (insular and infralimbic cortices notably) and the amygdala was observed. By contrast, poor decision-making was associated with a strikingly low recruitment of the prefronto-subcortical network, together with sustained amygdala activity. Our results identify two complementary neurobiological substrates characterizing poor decision-makers: imbalanced monoaminergic systems at rest, congruent with their previously identified complex behavioral phenotype, and an aberrant low recruitment of key brain areas for executive functions and affective valence during the process of decision-making. These biomarkers could sustain vulnerability to developing poor decision-making related disorders. PMID- 25134681 TI - Red cell distribution width is associated with incident myocardial infarction in a general population: the Tromso Study. AB - BACKGROUND: Red cell distribution width (RDW), a measure of the variability in size of circulating erythrocytes, is associated with mortality and adverse outcome in selected populations with cardiovascular disease. It is scarcely known whether RDW is associated with incident myocardial infarction (MI). We aimed to investigate whether RDW was associated with risk of first-ever MI in a large cohort study with participants recruited from a general population. METHODS AND RESULTS: Baseline characteristics, including RDW, were collected for 25 612 participants in the Tromso Study in 1994-1995. Incident MI during follow-up was registered from inclusion through December 31, 2010. Cox regression models were used to calculate hazard ratios with 95% confidence intervals for MI, adjusted for age, sex, body mass index, smoking, hemoglobin, white blood cells, platelets, and other traditional cardiovascular risk factors. A total of 1779 participants experienced a first-ever MI during a median follow-up time of 15.8 years. There was a linear association between RDW and risk of MI, for which a 1% increment in RDW was associated with a 13% increased risk (hazard ratio 1.13; 95% CI, 1.07 to 1.19). Participants with RDW above the 95th percentile had 71% higher risk of MI compared with those with RDW in the lowest quintile (hazard ratio 1.71; 95% CI, 1.34 to 2.20). All effect estimates were essentially similar after exclusion of participants with anemia (n=1297) from the analyses. CONCLUSION: RDW is associated with incident MI in a general population independent of anemia and cardiovascular risk factors. PMID- 25134684 TI - TMS stimulation over the inferior parietal cortex disrupts prospective sense of agency. AB - Sense of agency refers to the feeling of controlling an external event through one's own action. On one influential view, sense of agency is inferred after an action, by "retrospectively" comparing actual effects of actions against their intended effects. However, it has been recently shown that earlier processes, linked to action selection, may also contribute to sense of agency, in advance of the action itself, and independently of action effects. The inferior parietal cortex (IPC) may underpin this "prospective" contribution to agency, by monitoring signals relating to fluency of action selection in dorsolateral prefrontal cortex (DLPFC). Here, we combined transcranial stimulation (TMS) with subliminal priming of action selection to investigate the causal role of these regions in the prospective coding of agency. In a first experiment, we showed that TMS over left IPC at the time of action selection disrupts perceived control over subsequent effects of action. In a second experiment, we exploited the temporal specificity of single-pulse TMS to pinpoint the exact timing of IPC contribution to sense of agency. We replicated the reduction in perceived control at the point of action selection, while observing no effect of TMS-induced disruption of IPC at the time of action outcomes. PMID- 25134682 TI - Contralateral cerebello-thalamo-cortical pathways with prominent involvement of associative areas in humans in vivo. AB - In addition to motor functions, it has become clear that in humans the cerebellum plays a significant role in cognition too, through connections with associative areas in the cerebral cortex. Classical anatomy indicates that neo-cerebellar regions are connected with the contralateral cerebral cortex through the dentate nucleus, superior cerebellar peduncle, red nucleus and ventrolateral anterior nucleus of the thalamus. The anatomical existence of these connections has been demonstrated using virus retrograde transport techniques in monkeys and rats ex vivo. In this study, using advanced diffusion MRI tractography we show that it is possible to calculate streamlines to reconstruct the pathway connecting the cerebellar cortex with contralateral cerebral cortex in humans in vivo. Corresponding areas of the cerebellar and cerebral cortex encompassed similar proportion (about 80%) of the tract, suggesting that the majority of streamlines passing through the superior cerebellar peduncle connect the cerebellar hemispheres through the ventrolateral thalamus with contralateral associative areas. This result demonstrates that this kind of tractography is a useful tool to map connections between the cerebellum and the cerebral cortex and moreover could be used to support specific theories about the abnormal communication along these pathways in cognitive dysfunctions in pathologies ranging from dyslexia to autism. PMID- 25134685 TI - Chromophore composition of the phycobiliprotein Cr-PC577 from the cryptophyte Hemiselmis pacifica. AB - The cryptophyte phycocyanin Cr-PC577 from Hemiselmis pacifica is a close relative of Cr-PC612 found in Hemiselmis virescens and Hemiselmis tepida. The two biliproteins differ in that Cr-PC577 lacks the major peak at around 612 nm in the absorption spectrum. Cr-PC577 was thus purified and characterized with respect to its bilin chromophore composition. Like other cryptophyte phycobiliproteins, Cr PC577 is an (alphabeta)(alpha'beta) heterodimer with phycocyanobilin (PCB) bound to the alpha-subunits. While one chromophore of the beta-subunit is also PCB, mass spectrometry identified an additional chromophore with a mass of 585 Da at position beta-Cys-158. This mass can be attributed to either a dihydrobiliverdin (DHBV), mesobiliverdin (MBV), or bilin584 chromophore. The doubly linked bilin at position beta-Cys-50 and beta-Cys-61 could not be identified unequivocally but shares spectral features with DHBV. We found that Cr-PC577 possesses a novel chromophore composition with at least two different chromophores bound to the beta-subunit. Overall, our data contribute to a better understanding of cryptophyte phycobiliproteins and furthermore raise the question on the biosynthetic pathway of cryptophyte chromophores. PMID- 25134686 TI - Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV. AB - The integrase strand transfer inhibitors (INSTIs) are the newest antiretroviral class in the HIV treatment armamentarium. Dolutegravir (DTG) is the only second generation INSTI with FDA approval (2013). It has potential advantages in comparison to first-generation INSTI's, including unboosted daily dosing, limited cross resistance with raltegravir and elvitegravir, and a high barrier to resistance. Clinical trials have evaluated DTG as a 50-mg daily dose in both treatment-naive and treatment-experienced, INSTI-naive participants. In those treatment-naive participants with baseline viral load <100,000 copies/mL, DTG combined with abacavir and lamivudine was non-inferior and superior to fixed-dose combination emtricitabine/tenofovir/efavirenz. DTG was also superior to the protease inhibitor regimen darunavir/ritonavir in treatment-naive participants regardless of baseline viral load. Among treatment-experienced patients naive to INSTI, DTG (50 mg daily) demonstrated both non-inferiority and superiority when compared to the first-generation INSTI raltegravir (400 mg twice daily) regardless of the background regimen. No phenotypically significant DTG resistance has been demonstrated in INSTI-naive participant trials. The VIKING trials evaluated DTG's ability to treat persons with HIV with prior INSTI exposure. VIKING demonstrated twice-daily DTG was more efficacious than daily dosing when treating participants receiving and failing first-generation INSTI regimens. DTG maintained potency against single mutations from any of the three major INSTI pathways (Y143, H155, Q148); however, the Q148 mutation with two or more additional mutations significantly reduced its potency. The long-acting formulation of DTG, GSK1265744LA, is the next innovation in this second generation INSTI class, holding promise for the future of HIV prevention and treatment. PMID- 25134688 TI - Factors influencing knowledge and practice of hygiene in Water, Sanitation and Hygiene (WASH) programme areas of Bangladesh Rural Advancement Committee. AB - INTRODUCTION: Improved hygiene is one of the most effective means of reducing disease occurrence. However, a complete understanding of the factors that contribute to such improvement are not clear. This study explored factors that facilitate and/or impede hygiene behavior in water, sanitation and hygiene (WASH) intervention areas using qualitative research techniques. METHODS: The Bangladesh Rural Advancement Committee (BRAC) has been providing WASH intervention to 150 rural upazilas (sub-districts) since 2006. For qualitative data collection, in depth interviews were conducted with 144 purposively selected women from six upazilas across Bangladesh. A woman in the household was considered as a case and interviewed regarding various aspects of sanitation and hygiene, using a checklist. Some practices, such as cleanliness of latrines, and availability of soap, water, slippers in their designated place were physically verified. RESULTS: The respondents' hygiene behavior was mainly facilitated by improved knowledge and awareness of health and environment-related issues. Latrine ownership increased through financial assistance, resulting in improved privacy, social prestige, and a heightened sense of responsibility towards maintaining a healthy life. However, lack of interest in attending cluster meetings, traditional knowledge, poverty, and lack of will were some of the factors impeding knowledge and hygiene practice. In addition, attitude played a definitive role, with some respondents not practicing hygiene in spite of having the financial ability to do so. They expected full financial support for creating sanitation and hygiene facilities in their household despite BRAC's policy of providing such support only to the 'ultra-poor'. CONCLUSIONS: The identified impeding factors often act as barriers to transformation of hygiene-related knowledge into practice and practice into habit. More motivational cluster meetings with large-scale participation and periodic home visits by the programme organizers are imperative as they markedly improve hygiene behavior. PMID- 25134689 TI - Abstracts of the 50th EASD Annual Meeting, September 15-19, 2014, Vienna, Austria. PMID- 25134687 TI - Hypoxia-Inducible Factor (HIF) as a Pharmacological Target for Prevention and Treatment of Infectious Diseases. AB - In the present era of ever-increasing antibiotic resistance and increasingly complex and immunosuppressed patient populations, physicians and scientists are seeking novel approaches to battle difficult infectious disease conditions. Development of a serious infection implies a failure of innate immune capabilities in the patient, and one may consider whether pharmacological strategies exist to correct and enhance innate immune cell function. Hypoxia inducible factor-1 (HIF-1), the central regulator of the cellular response to hypoxic stress, has recently been recognized to control the activation state and key microbicidal functions of immune cells. HIF-1 boosting drugs are in clinical development for anemia and other indications, and could be repositioned as infectious disease therapeutics. With equal attention to opportunities and complexities, we review our current understanding of HIF-1 regulation of microbial host-pathogen interactions with an eye toward future drug development. PMID- 25134691 TI - Statistics: general linear models (a flexible approach). AB - This article moves on to discuss a type of statistical testing different from those we have discussed previously, namely a General Linear Model. This system incorporates a number of other statistical models and is a powerful tool used widely in modern statistics. PMID- 25134690 TI - Protocols utilizing constant pH molecular dynamics to compute pH-dependent binding free energies. AB - In protein-ligand binding, the electrostatic environments of the two binding partners may vary significantly in bound and unbound states, which may lead to protonation changes upon binding. In cases where ligand binding results in a net uptake or release of protons, the free energy of binding is pH-dependent. Nevertheless, conventional free energy calculations and molecular docking protocols typically do not rigorously account for changes in protonation that may occur upon ligand binding. To address these shortcomings, we present a simple methodology based on Wyman's binding polynomial formalism to account for the pH dependence of binding free energies and demonstrate its use on cucurbit[7]uril (CB[7]) host-guest systems. Using constant pH molecular dynamics and a reference binding free energy that is taken either from experiment or from thermodynamic integration computations, the pH-dependent binding free energy is determined. This computational protocol accurately captures the large pKa shifts observed experimentally upon CB[7]:guest association and reproduces experimental binding free energies at different levels of pH. We show that incorrect assignment of fixed protonation states in free energy computations can give errors of >2 kcal/mol in these host-guest systems. Use of the methods presented here avoids such errors, thus suggesting their utility in computing proton-linked binding free energies for protein-ligand complexes. PMID- 25134694 TI - Comment on "Effects of ethanol on vehicle energy efficiency and implications on ethanol life-cycle greenhouse gas analysis". PMID- 25134693 TI - Tasmanian Aborigines step up to health: evaluation of a cardiopulmonary rehabilitation and secondary prevention program. AB - BACKGROUND: Although the burden of cardiopulmonary diseases in the Aboriginal community is high, utilisation of rehabilitation services has been poor. We evaluated the uptake and effectiveness of a cardiovascular and pulmonary rehabilitation program specifically designed and provided for the Aboriginal community, by the Tasmanian Aboriginal Centre, for people with diagnosed chronic heart or respiratory disease and those at high risk of developing such conditions. METHODS: Participants had established chronic obstructive pulmonary disease, ischaemic heart disease or chronic heart failure or were at high risk of developing such diseases because of multiple risk factors. Rehabilitation programs (n = 13) comprised two exercise and one education session per week over eight weeks. Data, collected at baseline and on completion, included health status, risk factors, attendance, anthropometric measurements, physical capacity and quality of life. Data from participants who attended at least one program session were analysed. Qualitative written feedback from participants and staff was analysed thematically. RESULTS: Of 92 participants (39% with an established disease diagnosis), 72 provided follow-up data. Participants lost weight, and waist circumference decreased (mean -3.6 cm, 95% confidence interval (CI)-2.5 to 4.7). There were clinically significant improvements in six-minute walk distance (mean 55.7 m, 95% CI 37.8 to 73.7) and incremental shuttle walk (mean 106.2 m, 95% CI 79.1 to 133.2). There were clinically significant improvements in generic quality of life domains, dyspnoea and fatigue. Generally, the improvements in participants with established cardiac or respiratory diseases did not differ from that in people with risk factors. Analysis of qualitative data identified three factors that facilitated participation: support from peers and health workers, provision of transport and the program structure. Participants' awareness of improvements in their health contributed to ongoing participation and positive health outcomes, and participants would recommend the program to family and friends. CONCLUSION: A cardiopulmonary program, which included exercise and education and met national guidelines, was designed and delivered specifically for the Aboriginal community. It increased participation in rehabilitation by Aborigines with, or at high risk of, established disease and led to positive changes in health behaviours, functional exercise capacity and health related quality of life. PMID- 25134692 TI - Technology-assisted weight loss interventions in primary care: a systematic review. AB - BACKGROUND: The US Preventive Services Task Force recommends screening for and treating obesity. However, there are many barriers to successfully treating obesity in primary care (PC). Technology-assisted weight loss interventions offer novel ways of improving treatment, but trials are overwhelmingly conducted outside of PC and may not translate well into this setting. We conducted a systematic review of technology-assisted weight loss interventions specifically tested in PC settings. METHODS: We searched the literature from January 2000 to March 2014. INCLUSION CRITERIA: (1) Randomized controlled trial; (2) trials that utilized the Internet, personal computer, and/or mobile device; and (3) occurred in an ambulatory PC setting. We applied the Cochrane Effective Practice and Organization of Care (EPOC) and Delphi criteria to assess bias and the Pragmatic Explanatory Continuum Indicator Summary (PRECIS) criteria to assess pragmatism (whether trials occurred in the real world versus under ideal circumstances). Given heterogeneity, results were not pooled quantitatively. RESULTS: Sixteen trials met inclusion criteria. Twelve (75 %) interventions achieved weight loss (range: 0.08 kg - 5.4 kg) compared to controls, while 5-45 % of patients lost at least 5 % of baseline weight. Trial duration and attrition ranged from 3-36 months and 6-80 %, respectively. Ten (63 %) studies reported results after at least 1 year of follow-up. Interventions used various forms of personnel, technology modalities, and behavior change elements; trials most frequently utilized medical doctors (MDs) (44 %), web-based applications (63 %), and self monitoring (81 %), respectively. Interventions that included clinician-guiding software or feedback from personnel appeared to promote more weight loss than fully automated interventions. Only two (13 %) studies used publically available technologies. Many studies had fair pragmatism scores (mean: 2.8/4), despite occurring in primary care. DISCUSSION: Compared to usual care, technology assisted interventions in the PC setting help patients achieve weight loss, offering evidence-based options to PC providers. However, best practices remain undetermined. Despite occurring in PC, studies often fall short in utilizing pragmatic methodology and rarely provide publically available technology. Longitudinal, pragmatic, interdisciplinary, and open-source interventions are needed. PMID- 25134695 TI - A joint history of the nature of genetic variation and the nature of schizophrenia. AB - This essay traces the history of concepts of genetic variation and schizophrenia from Darwin and Mendel to the present. For Darwin, the important form of genetic variation for evolution is continuous in nature and small in effect. Biometricians led by Pearson agreed and developed statistical genetic approaches utilizing trait correlations in relatives. Mendel studied discontinuous traits and subsequent Mendelians, led by Bateson, assumed that important genetic variation was large in effect producing discontinuous phenotypes. Although biometricians studied 'insanity', schizophrenia genetics under Kraepelin and Rudin utilized Mendelian approaches congruent with their anatomical-clinical disease model of dementia praecox. Fisher showed, assuming many genes of small effect, Mendelian and Biometrical models were consilient. Echoing prior conflicts, psychiatric genetics since then has utilized both biometrical models, largely in twins, and Mendelian models, based on advancing molecular techniques. In 1968, Gottesman proposed a polygenic model for schizophrenia based on a threshold version of Fisher's theory. Since then, rigorous studies of the schizophrenia spectrum suggest that genetic risk for schizophrenia is more likely continuous than categorical. The last 5 years has seen increasingly convincing evidence from genome-wide association study (GWAS) and sequencing that genetic risk for schizophrenia is largely polygenic, and congruent with Fisher's and Gottesman's models. The gap between biometrical and molecular Mendelian models for schizophrenia has largely closed. The efforts to ground a categorical biomedical model of schizophrenia in Mendelian genetics have failed. The genetic risk for schizophrenia is widely distributed in human populations so that we all carry some degree of risk. PMID- 25134703 TI - Neuro-oncology: It takes two to tango. PMID- 25134696 TI - High prevalence of Toxoplasma gondii antibodies in dogs in Veracruz, Mexico. AB - BACKGROUND: Little is known concerning the prevalence of Toxoplasma gondii infection in dogs in Mexico. Here, we investigated antibodies to T. gondii and associated risk factors in 101 dogs from an animal shelter in Veracruz State, Mexico. Canine sera were assayed for T. gondii IgG antibodies by using the modified agglutination test (MAT, cut off 1:25). RESULTS: Sixty eight (67.3%) of 101 dogs were seropositive with titers of 1:25 in 16, 1:50 in 8, 1:100 in 9, 1:200 in 10, 1:400 in 10, 1:800 in 10, 1:1600 in 3, and 1:3200 or higher in 2. None of the dogs' characteristics studied including age, sex, breed, and history of deworming, rabies vaccination and contact with cats was associated with seroprevalence of T. gondii infection. CONCLUSION: Using the dogs as sentinel animals, the results indicate high contamination with T. gondii of the environment in Veracruz, Mexico. Results have public health implications, and further studies in Veracruz should be conducted to establish the sources of environmental contamination with T. gondii and to determine optimal preventive measures against T. gondii infection in humans. PMID- 25134706 TI - Alzheimer disease: Functional connectivity changes show similar trajectories in autosomal dominant and sporadic Alzheimer disease. PMID- 25134709 TI - Parkinson disease: Can a new trial end controversy over when to use levodopa? AB - Levodopa is the standard therapy for Parkinson disease, but prolonged use promotes the development of adverse motor effects. A new trial compared the effectiveness of levodopa administration early in the disease with therapies that used alternative dopaminergic agents before levodopa. No clinically relevant differences were found between the treatment strategies. PMID- 25134708 TI - Mechanism-based treatment in complex regional pain syndromes. AB - Complex regional pain syndromes (CRPS) are multifactorial disorders with complex aetiology and pathogenesis. Management of CRPS is challenging, partly because of a lack of clinical data regarding the efficacy of the various therapies, and partly because successful treatment of CRPS requires a multidisciplinary, patient tailored approach. The pain in CRPS is often described as typical 'burning' neuropathic pain, and is accompanied by a variety of sensory, motor and autonomic signs and symptoms. Because research into therapies specifically in CRPS has been scarce, treatment for these syndromes has been largely based on therapeutic strategies adapted from neuropathic pain states; however, increased understanding of the pathogenesis of CRPS has provided the opportunity to develop mechanism based treatments. The interactions between the multiple pathophysiological mechanisms that contribute to the development, progression and maintenance of CRPS remain poorly understood. This Review describes the challenges in linking the current theories and knowledge of pathophysiological mechanisms to the mode of actions of the different treatment approaches. We discuss the current treatment strategies for CRPS, including pharmacotherapy, sympathetic ganglion block interventions, psychological support, physiotherapy and occupational therapy, and establish the concept of mechanism-based treatment for CRPS. PMID- 25134717 TI - Why it is scientifically respectable to believe in repression: a response to Patihis, Ho, Tingen, Lilienfeld, and Loftus (2014). PMID- 25134716 TI - Unconscious repressed memory is scientifically questionable. PMID- 25134715 TI - The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility. AB - The interplay between long-term potentiation and long-term depression (LTD) is thought to be involved in learning and memory formation. One form of LTD expressed in the hippocampus is initiated by the activation of the group 1 metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown to be critical for acquisition of new memories and for reversal learning, processes that are thought to be crucial for cognitive flexibility. Here we provide evidence that MAPK-activated protein kinases 2 and 3 (MK2/3) regulate neuronal spine morphology, synaptic transmission and plasticity. Furthermore, mGluR-LTD is impaired in the hippocampus of MK2/3 double knockout (DKO) mice, an observation that is mirrored by deficits in endocytosis of GluA1 subunits. Consistent with compromised mGluR-LTD, MK2/3 DKO mice have distinctive deficits in hippocampal dependent spatial reversal learning. These novel findings demonstrate that the MK2/3 cascade plays a strategic role in controlling synaptic plasticity and cognition. PMID- 25134719 TI - Digital necrosis after triamcinolone acetonide injection for trigger thumb: case report. PMID- 25134718 TI - Analysis of high fat diet induced genes during mammary gland development: identifying role players in poor prognosis of breast cancer. AB - BACKGROUND: Epidemiological studies have shown that consumption of a high-fat diet (HFD) increases the risk of developing breast cancer (BC). Studies in rodents have shown HFD causes changes in the genetic programming of the maturing mammary gland (MG) increasing the susceptibility of developing the disease. Less is known about how HFD induced genes impact BC development. HFD exposure two weeks before conception to six weeks of age was previously shown to dramatically change MG gene expression in 10 week old mice. Therefore, we investigated these differentially expressed HFD-induced genes for their expression in BC using the NKI 295 breast tumor dataset. RESULTS: To examine the potential role of HFD induced genes in BC, we first investigated whether these HFD-induced genes in mouse MGs were differentially expressed in different types of human BC. Of the 28 HFD induced genes that were differentially expressed between BC subtypes in the NKI set, 79% were significantly higher in basal-like BC. Next, we analyzed whether HFD induced genes were associated with BC prognosis utilizing gene expression and survival data for each HFD induced gene from the NKI data and constructed Kaplan Meier survival plots. Significantly, 93% of the prognosis associated genes (13/14) were associated with poor prognosis (P = 0.002). Kaplan Meier analysis with 249 non-basal-like BC found that all but one of the genes examined were still significantly associated with poor prognosis. Furthermore, gene set enrichment analysis (GSEA) with HFD microarray data revealed that invasive BC genes where enriched in HFD samples that also had lost expression of luminal genes. CONCLUSIONS: HFD exposed mouse MGs maintain differential expression of genes that are found highly expressed in basal-like breast cancer. These HFD-induced genes associate with poor survival in numerous BC subtypes, making them more likely to directly impact prognosis. Furthermore, HFD exposure leads to a loss in the expression of luminal genes and a gain in expression of mesenchymal and BC invasion genes in MGs. Collectively, our study suggests that HFD exposure during development induces genes associated with poor prognosis, thus identifying how HFD diet may regulate BC development. PMID- 25134720 TI - Candida haemulonii complex: species identification and antifungal susceptibility profiles of clinical isolates from Brazil. AB - OBJECTIVES: The emerging fungal pathogens comprising the Candida haemulonii complex (Candida haemulonii, Candida haemulonii var. vulnera and Candida duobushaemulonii) are notable for their antifungal resistance. Twelve isolates with phenotypic similarity to C. haemulonii were recovered from patients in Brazilian hospitals. Here we aimed to identify these isolates by a molecular approach, using the current classification of this fungal complex, and to evaluate their antifungal susceptibility profiles. METHODS: The fungal isolates were rechecked to certify their authentication by mycology methodologies and then characterized by ITS1-5.8S-ITS2 gene sequencing. A susceptibility assay was performed using the broth microdilution method published by CLSI (M27-A3/M27-S3). RESULTS: Based on biochemical tests, all Brazilian isolates were identified as C. haemulonii. After employing ITS sequencing, five isolates were identified as C. haemulonii, four as C. duobushaemulonii and three as C. haemulonii var. vulnera. All 12 clinical isolates were resistant to amphotericin B (MICs ranged from 2 to >16 mg/L) and fluconazole (MICs >= 64 mg/L). One isolate of C. haemulonii var. vulnera and two isolates of C. duobushaemulonii were susceptible-dose dependent to itraconazole, while the remaining isolates (75%) were resistant to this antifungal. Eight out of 12 isolates (66.7%) were resistant to voriconazole (MICs >= 16 mg/L), while all isolates were susceptible to caspofungin (MICs <= 0.5 mg/L). CONCLUSIONS: Our results reinforce the importance of molecular identification in differentiating species of the C. haemulonii complex. Moreover, the antifungal multiresistant profile of clinical isolates of the C. haemulonii complex represents a challenge to the treatment of such infections. PMID- 25134721 TI - Activity of the type I signal peptidase inhibitor MD3 against multidrug-resistant Gram-negative bacteria alone and in combination with colistin. AB - OBJECTIVES: Effective treatment of Gram-negative bacterial infections is increasingly challenging due to the spread of multidrug-resistant strains and a lack of new antimicrobials in development. Bacterial type I signal peptidases (SPases) represent a highly conserved and essential target for inhibition by novel compounds. SPases are required for the effective processing of membrane translocated proteins involved in core functions related to metabolism, virulence and resistance. In this study we assessed the biochemical and functional activity of a novel synthetic inhibitor (MD3) of SPases against a wide range of Gram negative pathogens. METHODS: The activity and specificity of MD3 for recombinant Pseudomonas aeruginosa SPase (LepB) and a genetically engineered LepB-regulatable strain were investigated. Antimicrobial activity of the compound alone and in combination with outer membrane-permeabilizing agents (sodium hexametaphosphate, colistin) was also determined against a collection of P. aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Stenotrophomonas maltophilia isolates. RESULTS: MD3 was found to inactivate the P. aeruginosa LepB protein (IC50 10 MUM), resulting in antimicrobial effects potentiated in the presence of colistin. MD3 also demonstrated potent activity against wild-type and multidrug resistant strains of A. baumannii and S. maltophilia with MICs ranging from 0.5 to 14 mg/L in the presence of subinhibitory concentrations of colistin. CONCLUSIONS: MD3 is a novel inhibitor of bacterial SPase in a range of non fermentative Gram-negative bacteria. The antimicrobial activity is potentiated in combination with colistin and suggests that SPase inhibition warrants further exploration as a basis for future mono or combination therapies. PMID- 25134722 TI - Consumption of highly processed snacks, sugar-sweetened beverages and child feeding practices in a rural area of Nicaragua. AB - Appropriate feeding behaviours are important for child growth and development. In societies undergoing nutrition transition, new food items are introduced that may be unfavourable for child health. Set in rural Nicaragua, the aim of this study was to describe the infant and young child feeding (IYCF) practices as well as the consumption of highly processed snack foods (HP snacks) and sugar-sweetened beverages (SSBs). All households with at least one child 0- to 35-month-old (n = 1371) were visited to collect information on current IYCF practices in the youngest child as well as consumption of SSBs and HP snacks. Breastfeeding was dominant (98%) among 0- to 1-month-olds and continued to be prevalent (60%) in the second year, while only 34% of the 0- to 5-month-olds were exclusively breastfed. Complementary feeding practices were deemed acceptable for only 59% of the 6- to 11-month-old infants, with low dietary diversity reported for 50% and inadequate meal frequency reported for 30%. Consumption of HP snacks and SSBs was frequent and started early; among 6- to 8-month-olds, 42% and 32% had consumed HP snacks and SSBs, respectively. The difference between the observed IYCF behaviours and World Health Organization recommendations raises concern of increased risk of infections and insufficient intake of micronutrients that may impair linear growth. The concurrent high consumption of SSBs and HP snacks may increase the risk of displacing the recommended feeding behaviours. To promote immediate and long-term health, growth and development, there is a need to both promote recommended IYCF practices as well as discourage unfavourable feeding behaviours. PMID- 25134724 TI - Early investigational drugs that target epidermal growth factor receptors for the treatment of head and neck cancer. AB - INTRODUCTION: Squamous-cell carcinoma of the head and neck (SCCHN) remains a challenging clinical problem, due to the persistent high rate of local and distant failures and the occurrence of secondary primaries. For locally advanced SCCHN, a combination of chemotherapy (CT), radiation or surgery is often used, but there are limitations, which may reduce compliance. Molecular targeted therapies, namely anti-EGFR treatments, are in development with the aim of improving clinical outcomes and mitigating treatment-related toxicities. AREAS COVERED: This review provides an overview of early investigational drugs that target EGFR for the treatment of SCCHN and discusses the ongoing trials in this domain. EXPERT OPINION: Targeted therapies are increasingly used in oncology, especially in SCCHN. Cetuximab has demonstrated a significant improvement in the treatment outcome, both as a curative treatment in combination with radiation therapy and as a palliative treatment in combination with CT; however, it failed to show any benefit in combination with concomitant chemoradiotherapy. Presently, there are many new agents, including monoclonal antibodies and small-molecule tyrosine kinase inhibitors, which are either currently under investigation for or which warrant further investigation for treating SCCHN. The discovery of predictive factors that help to identify patients most likely to respond to EGFR inhibitors as well as patient-customized therapies would help to improve patient outcomes in the future. PMID- 25134725 TI - Unified theory of electron-phonon renormalization and phonon-assisted optical absorption. AB - We present a theory of electronic excitation energies and optical absorption spectra which incorporates energy-level renormalization and phonon-assisted optical absorption within a unified framework. Using time-independent perturbation theory we show how the standard approaches for studying vibronic effects in molecules and those for addressing electron-phonon interactions in solids correspond to slightly different choices for the non-interacting Hamiltonian. Our present approach naturally leads to the Allen-Heine theory of temperature-dependent energy levels, the Franck-Condon principle, the Herzberg Teller effect and to phonon-assisted optical absorption in indirect band gap materials. In addition, our theory predicts sub-gap phonon-assisted optical absorption in direct gap materials, as well as an exponential edge which we tentatively assign to the Urbach tail. We also consider a semiclassical approach to the calculation of optical absorption spectra which simultaneously captures energy-level renormalization and phonon-assisted transitions and is especially suited to first-principles electronic structure calculations. We demonstrate this approach by calculating the phonon-assisted optical absorption spectrum of bulk silicon. PMID- 25134723 TI - The ceramide kinase inhibitor NVP-231 inhibits breast and lung cancer cell proliferation by inducing M phase arrest and subsequent cell death. AB - BACKGROUND AND PURPOSE: Ceramide kinase (CerK) catalyzes the generation of ceramide-1-phosphate which may regulate various cellular functions, including inflammatory reactions and cell growth. Here, we studied the effect of a recently developed CerK inhibitor, NVP-231, on cancer cell proliferation and viability and investigated the role of cell cycle regulators implicated in these responses. EXPERIMENTAL APPROACH: The breast and lung cancer cell lines MCF-7 and NCI-H358 were treated with increasing concentrations of NVP-231 and DNA synthesis, colony formation and cell death were determined. Flow cytometry was performed to analyse cell cycle distribution of cells and Western blot analysis was used to detect changes in cell cycle regulator expression and activation. KEY RESULTS: In both cell lines, NVP-231 concentration-dependently reduced cell viability, DNA synthesis and colony formation. Moreover it induced apoptosis, as measured by increased DNA fragmentation and caspase-3 and caspase-9 cleavage. Cell cycle analysis revealed that NVP-231 decreased the number of cells in S phase and induced M phase arrest with an increased mitotic index, as determined by increased histone H3 phosphorylation. The effect on the cell cycle was even more pronounced when NVP-231 treatment was combined with staurosporine. Finally, overexpression of CerK protected, whereas down-regulation of CerK with siRNA sensitized, cells for staurosporine-induced apoptosis. CONCLUSIONS AND IMPLICATIONS: Our data demonstrate for the first time a crucial role for CerK in the M phase control in cancer cells and suggest its targeted inhibition, using drugs such as NVP-231, in combination with conventional pro-apoptotic chemotherapy. PMID- 25134726 TI - Graphene oxide amplifies the phytotoxicity of arsenic in wheat. AB - Graphene oxide (GO) is widely used in various fields and is considered to be relatively biocompatible. Herein, "indirect" nanotoxicity is first defined as toxic amplification of toxicants or pollutants by nanomaterials. This work revealed that GO greatly amplifies the phytotoxicity of arsenic (As), a widespread contaminant, in wheat, for example, causing a decrease in biomass and root numbers and increasing oxidative stress, which are thought to be regulated by its metabolisms. Compared with As or GO alone, GO combined with As inhibited the metabolism of carbohydrates, enhanced amino acid and secondary metabolism and disrupted fatty acid metabolism and the urea cycle. GO also triggered damage to cellular structures and electrolyte leakage and enhanced the uptake of GO and As. Co-transport of GO-loading As and transformation of As(V) to high-toxicity As(III) by GO were observed. The generation of dimethylarsinate, produced from the detoxification of inorganic As, was inhibited by GO in plants. GO also regulated phosphate transporter gene expression and arsenate reductase activity to influence the uptake and transformation of As, respectively. Moreover, the above effects of GO were concentration dependent. Given the widespread exposure to As in agriculture, the indirect nanotoxicity of GO should be carefully considered in food safety. PMID- 25134727 TI - Amyloid-beta oligomers as a template for secondary amyloidosis in Alzheimer's disease. AB - Alzheimer's disease is a complex disease characterized by overlapping phenotypes with different neurodegenerative disorders. Oligomers are considered the most toxic species in amyloid pathologies. We examined human AD brain samples using an anti-oligomer antibody generated in our laboratory and detected potential hybrid oligomers composed of amyloid-beta, prion protein, alpha-synuclein, and TDP-43 phosphorylated at serines 409 and 410. These data and in vitro results suggest that Abeta oligomer seeds act as a template for the aggregation of other proteins and generate an overlapping phenotype with other neuronal disorders. Furthermore, these results could explain why anti-amyloid-beta therapy has been unsuccessful. PMID- 25134729 TI - Phosphorylated tau potentiates Abeta-induced mitochondrial damage in mature neurons. AB - Tau phosphorylated at the PHF-1 epitope (S396/S404) is likely involved in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which tau phosphorylated at these sites negatively impacts neuronal functions are still under scrutiny. Previously, we showed that expression of tau truncated at D421 enhances mitochondrial dysfunction induced by Abeta in cortical neurons. To extend these findings, we expressed tau pseudo-phosphorylated at S396/404 (T42EC) in mature and young cortical neurons and evaluated different aspects of mitochondrial function in response to Abeta. Expression of T42EC did not induce significant changes in mitochondrial morphology, mitochondrial length, or mitochondrial transport, compared to GFP and full-length tau. However, T42EC expression enhanced Abeta-induced mitochondrial membrane potential loss and increased superoxide levels compared to what was observed in mature neurons expressing full-length tau. The same effect was observed in mature neurons that expressed both pseudo-phosphorylated and truncated tau when they were treated with Abeta. Interestingly, the mitochondrial failure induced by Abeta in mature neurons that expressed T42EC, was not observed in young neurons expressing T42EC. These novel findings suggest that phosphorylated tau (PHF-1 epitope) enhances Abeta-induced mitochondrial injury, which contributes to neuronal dysfunction and to the pathogenesis of AD. PMID- 25134730 TI - Dynamic changes in pro- and anti-inflammatory cytokines in microglia after PPAR gamma agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson's disease. AB - Neuroinflammatory changes play a pivotal role in the progression of Parkinson's disease (PD) pathogenesis. Recent findings have suggested that activated microglia may polarize similarly to peripheral macrophages in the central nervous system (CNS), assuming a pro-inflammatory M1 phenotype or the alternative anti inflammatory M2 phenotype via cytokine production. A skewed M1 activation over M2 has been related to disease progression in Alzheimer disease, and modulation of microglia polarization may be a therapeutic target for neuroprotection. By using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-probenecid (MPTPp) mouse model of progressive PD, we investigated dynamic changes in the production of pro inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, and anti-inflammatory cytokines, such as transforming growth factor (TGF)-beta and IL-10, within Iba-1-positive cells in the substantia nigra compacta (SNc). In addition, to further characterize changes in the M2 phenotype, we measured CD206 in microglia. Moreover, in order to target microglia polarization, we evaluated the effect of the peroxisome-proliferator-activated receptor (PPAR)-gamma agonist rosiglitazone, which has been shown to exert neuroprotective effects on nigral dopaminergic neurons in PD models, and acts as a modulator of cytokine production and phenotype in peripheral macrophages. Chronic treatment with MPTPp induced a progressive degeneration of SNc neurons. The neurotoxin treatment was associated with a gradual increase in both TNF-alpha and IL-1beta colocalization with Iba-1-positive cells, suggesting an increase in pro-inflammatory microglia. In contrast, TGF-beta colocalization was reduced by the neurotoxin treatment, while IL-10 was mostly unchanged. Administration of rosiglitazone during the full duration of MPTPp treatment reverted both TNF-alpha and IL-1beta colocalization with Iba-1 to control levels. Moreover, rosiglitazone induced an increase in TGF-beta and IL-10 colocalization compared with the MPTPp treatment. CD206 was gradually reduced by the chronic MPTPp treatment, while rosiglitazone restored control levels, suggesting that M2 anti-inflammatory microglia were stimulated and inflammatory microglia were inhibited by the neuroprotective treatment. The results show that the dopaminergic degeneration was associated with a gradual microglia polarization to the inflammatory over the anti-inflammatory phenotype in a chronic mouse model of PD. Neuroprotective treatment with rosiglitazone modulated microglia polarization, boosting the M2 over the pro-inflammatory phenotype. PPAR-gamma agonists may offer a novel approach to neuroprotection, acting as disease-modifying drugs through an immunomodulatory action in the CNS. PMID- 25134728 TI - Genetic rescue of CB1 receptors on medium spiny neurons prevents loss of excitatory striatal synapses but not motor impairment in HD mice. AB - Huntington's disease (HD) is caused by an expanded polyglutamine repeat in huntingtin protein that disrupts synaptic function in specific neuronal populations and results in characteristic motor, cognitive and affective deficits. Histopathological hallmarks observed in both HD patients and genetic mouse models include the reduced expression of synaptic proteins, reduced medium spiny neuron (MSN) dendritic spine density and decreased frequency of spontaneous excitatory post-synaptic currents (sEPSCs). Early down-regulation of cannabinoid CB1 receptor expression on MSN (CB1(MSN)) is thought to participate in HD pathogenesis. Here we present a cell-specific genetic rescue of CB1(MSN) in R6/2 mice and report that treatment prevents the reduction of excitatory synaptic markers in the striatum (synaptophysin, vGLUT1 and vGLUT2), of dendritic spine density on MSNs and of MSN sEPSCs, but does not prevent motor impairment. We conclude that loss of excitatory striatal synapses in HD mice is controlled by CB1(MSN) and can be uncoupled from the motor phenotype. PMID- 25134732 TI - Thermoplastic properties of endodontic gutta-percha: a thermographic in vitro study. AB - INTRODUCTION: Endodontic gutta-percha undergoes deformation at temperatures above 65 degrees C. The temperature influence of heat carriers on gutta-percha cones was investigated in vitro. METHODS: Six single-rooted extracted teeth were embedded in resin and fixed. The root canals were prepared (ProFile; Dentsply Maillefer, Ballaiques, Switzerland) to different tapers and bisected. Thermographic images when heating the gutta-percha cones (Roeko, Langenau, Germany) with a heat carrier (ML .12; SybronEndo, Orange, CA) at 1 and 5 mm from the working length were made with an infrared thermal imaging camera (ThermaCam P640; Flir Systems, Taby, Sweden). The device temperature was preset at 200 degrees C. The pixel temperature registered at the contact lines between the heat carriers and gutta-percha cones in the thermographic images was recorded and statistically described. RESULTS: A mean temperature ( degrees C) instability in the heat carrier (324.96 +/- 46.10, minimum = 147.35, maximum = 474.13), a temperature drop of the gutta-percha cones (159.52, +/- 37.57, min 67.64, max 259.04) at the measuring level, and a mean temperature penetration depth (mm) equal or to higher than 65 degrees C (1.05 +/- 0.28, minimum = 0.20, maximum = 1.30) were recorded. No correlation between the penetration depth into the gutta percha cones and applied temperatures, regardless of the size and/or taper, could be established. CONCLUSIONS: Temperature discrepancies between the device preset and achieved ones of the heat carriers was observed. Gutta-percha is a poor thermal conductor, transports heat irregularly, and should be heated 1-2 mm from the target area. PMID- 25134733 TI - Autogenous premolar transplantation into artificial socket in maxillary lateral incisor site. AB - INTRODUCTION: Autogenous transplantation of a natural tooth to another site has significant advantages over dental implants, particularly in cases of agenesis, accidental tooth loss, or poor prognosis for the maintenance of tooth function. METHODS: This report describes a case of autogenous premolar transplantation into an artificial socket in the site of a missing maxillary lateral incisor in a 13 year-old girl. Clinical examination and radiography revealed tooth agenesis (#4, #10, #13, and #20) and microdontia (#7). The occlusion and skeletal maxillomandibular relations were normal. RESULTS: Tooth #29 was chosen for transplantation into the site of tooth #10 because of its size, stage of root formation, and possible closure of the spaces created by agenesis. CONCLUSIONS: Autogenous transplantation is a feasible alternative to dental implants in cases of tooth agenesis or tooth loss because of trauma. Autotransplantation was indicated in this case because it ensures the natural (facial) growth of the alveolar process and preserves the function of periodontal tissues. A multidisciplinary approach (ie, combining techniques from different dental specialties) was important for treatment success. Clinical and radiographic follow-up confirmed that the transplanted premolar was esthetically comparable with the lateral incisor and that root development and pulp canal obliteration were complete. PMID- 25134731 TI - Guanabenz, which enhances the unfolded protein response, ameliorates mutant SOD1 induced amyotrophic lateral sclerosis. AB - Approximately 20% of familial amyotrophic lateral sclerosis (FALS) cases are caused by mutant superoxide dismutase type 1 (mtSOD1). Although the mechanisms of mtSOD1-induced toxicity remain poorly understood, evidence suggests that accumulation of misfolded SOD1 is fundamental to its toxicity and the death of motor neurons. Misfolded mtSOD1 can accumulate inside the endoplasmic reticulum (ER), leading to ER stress, with activation of the unfolded protein response (UPR). We have previously carried out genetic studies focused on PERK (which is an eIF2alpha kinase that is rapidly activated in response to ER stress and leads to a repression in translation) and GADD34 (which participates in the dephosphorylation of eIF2alpha). We reported that mtSOD1 transgenic mice that are haploinsufficient for PERK have a significantly accelerated ALS disease, while mtSOD1 mice that are mutated for GADD34 have a remarkably ameliorated disease. Guanabenz, a centrally acting oral drug approved for the treatment of hypertension, enhances the PERK pathway by selectively inhibiting GADD34-mediated dephosphorylation of eIF2alpha. We have now treated G93A mtSOD1 transgenic mice with guanabenz and found a significant amelioration of disease with a delay in the onset and prolongation of the early phase of disease and survival. Guanabenz treated G93A mice have less accumulation of mtSOD1 and an enhanced phosphorylation of eIF2alpha at endstage. This study further emphasizes the importance of the PERK pathway in the pathogenesis of FALS and as a therapeutic target in ALS, and identifies guanabenz as a candidate drug for the treatment of ALS patients. PMID- 25134734 TI - Effects of WNT10A on proliferation and differentiation of human dental pulp cells. AB - INTRODUCTION: Wingless-type MMTV integration site family, member 10A (WNT10A) plays crucial roles in odontogenesis. The aim of this study was to investigate the effects of WNT10A on human dental pulp cells (DPCs), which contain a mixed population of cells, including stem and progenitor cells, and participate in dentin repair or dentin-pulp regeneration. METHODS: Healthy human premolars extracted for orthodontic reasons were used as a study model. The expression of WNT10A protein in dental pulp was determined by immunohistochemistry. The messenger RNA expression of WNT10A and Wnt-related genes was analyzed by semiquantitative reverse-transcription polymerase chain reaction. DPCs were enzymatically separated from pulp tissues, cultured, and passaged. The biological effects of WNT10A on DPCs were investigated using recombinant lentivirus encoding WNT10A complementary DNA. WNT10A-induced changes in DPC proliferation were assessed by methyltetrazolium assay and flow cytometry. In order to determine the effects of WNT10A on DPC differentiation, the activity of alkaline phosphatase (ALP), an early marker of odontoblastic differentiation, was assessed using an ALP activity assay kit, and the expression levels of odontoblast-specific genes, including DSPP, DMP1, ALP, and COL1A1, were detected by quantitative polymerase chain reaction and Western blot. RESULTS: WNT10A protein was clearly identified in the cytoplasm of DPCs. Semiquantitative reverse-transcription polymerase chain reaction indicated the expression of WNT10A and Wnt-related genes in pulp tissues as well as in passaging DPCs. Lentiviral overexpression of WNT10A enhanced proliferation of DPCs and down-regulated ALP activity and the expression of odontoblast-specific genes. CONCLUSIONS: WNT10A promotes the proliferation of DPCs and negatively regulates their odontoblastic differentiation. PMID- 25134735 TI - Evolutionary dynamics of R2 retroelement and insertion inheritance in the genome of bisexual and parthenogenetic Bacillus rossius populations (Insecta Phasmida). AB - Theoretical and empirical studies have shown differential management of transposable elements in organisms with different reproductive strategies. To investigate this issue, we analysed the R2 retroelement structure and variability in parthenogenetic and bisexual populations of Bacillus rossius stick insects, as well as insertions inheritance in the offspring of parthenogenetic isolates and of crosses. The B. rossius genome hosts a functional (R2Br(fun) ) and a degenerate (R2Br(deg) ) element, their presence correlating with neither reproductive strategies nor population distribution. The median-joining network method indicated that R2Br(fun) duplicates through a multiple source model, while R2Br(deg) is apparently still duplicating via a master gene model. Offspring analyses showed that unisexual and bisexual offspring have a similar number of R2Br-occupied sites. Multiple or recent shifts from gonochoric to parthenogenetic reproduction may explain the observed data. Moreover, insertion frequency spectra show that higher-frequency insertions in unisexual offspring significantly outnumber those in bisexual offspring. This suggests that unisexual offspring eliminate insertions with lower efficiency. A comparison with simulated insertion frequencies shows that inherited insertions in unisexual and bisexual offspring are significantly different from the expectation. On the whole, different mechanisms of R2 elimination in unisexual vs bisexual offspring and a complex interplay between recombination effectiveness, natural selection and time can explain the observed data. PMID- 25134737 TI - Memory processes in the development of reduced-salt foods. AB - Acceptance of a reduced-salt food is likely to be influenced by a mismatch between the sensory characteristics of a reformulated product and a memory for a previously-encountered formulation. In two initial pilot studies we established the reliability of a new measure of memory for saltiness, based on a method of constant stimuli. We then used this technique to explore the effects of different patterns of repeated exposure on memory for the taste of a reduced-salt soup. Participants (N = 135) were assigned to one of four exposure patterns: (1) reduced-salt, (2) no salt reduction, i.e. regular-salt, (3) reduced- and regular salt, in an alternating pattern, and (4) gradually declining salt concentration. In the final session, all participants received an identical reduced-salt soup. Memory for the saltiness of this sample was assessed, together with its expected liking. Our results indicate that different interactions with the test soup had little effect on taste memory. Nevertheless, (1) participants remembered the final exposure soup as saltier than the reduced-salt formulation that they had received and (2) remembered salt concentrations correlated with individual ideal salt concentrations. These findings are consistent with contemporary models of reconstructive memory and they illustrate the importance of understanding 'memory for saltiness' in the acceptance of reduced-salt formulations. PMID- 25134736 TI - Interpersonal motives and social-evaluative threat: Effects of acceptance and status stressors on cardiovascular reactivity and salivary cortisol response. AB - Social-evaluative threat evokes increases in salivary cortisol and heightened cardiovascular reactivity. However, the types or content of social threats underlying these physiological responses are not clearly delineated in direct comparisons. Based in interpersonal theory, the present study manipulated high and low levels of acceptance threat (i.e., evaluation of likability, potential for inclusion) and status threat (i.e., evaluation of competence, leadership potential) during a modified Trier Social Stress Test, using a sample of 137 undergraduates (73 women). Both acceptance threat and status threat heightened salivary cortisol, heart rate, and blood pressure responses to the task. Hence, concerns about social inclusion or connection with others and concerns about social standing or status can contribute independently to physiological stress responses. PMID- 25134738 TI - Bidirectional associations between binge eating and restriction in anorexia nervosa. An ecological momentary assessment study. AB - This study examined the association between restrictive eating behaviors and binge eating in anorexia nervosa (AN) using data collected in the natural environment. Women (N = 118) with DSM-IV full or subthreshold AN reported eating disorder behaviors, including binge eating episodes, going >= 8 waking hours without eating, and skipping meals, during 2 weeks of ecological momentary assessment (EMA). Time-lagged generalized estimating equations tested the following hypotheses: 1) dietary restriction would predict binge eating while controlling for binge eating the previous day; 2) binge eating would predict restriction the subsequent day while controlling for restriction the previous day. After controlling for relevant covariates, the hypotheses were not supported; however, there appeared to be a cumulative effect of repeatedly going 8 consecutive hours without eating (i.e. fasting) on the risk of binge eating among individuals who recently engaged in binge eating. In addition, skipping meals was associated with a lower risk of same day binge eating. The relationship between binge eating and dietary restriction appears to be complex and may vary by type of restrictive eating behavior. Future research should aim to further clarify the nature of the interaction of binge eating and restrictive eating among individuals with AN in order to effectively eliminate these behaviors in treatment. PMID- 25134741 TI - Knee arthrotomy closure with barbed suture in flexion versus extension: a porcine study. AB - The purpose of this biomechanical study was to evaluate knee arthrotomy closure with a barbed suture in flexion versus extension. 48 porcine knees were randomized into three groups: full extension, 30 degrees flexion, and 60 degrees flexion. Each knee was then flexed to 90 degrees and then 120 degrees , with failures recorded. Arthrotomy closure in extension had significantly higher failure rates (6/16) upon flexion to 90 degrees compared to arthrotomy closure in either 30 degrees or 60 degrees flexion (0/32) (P = 0.032). Upon ranging from 0 degrees to 120 degrees , arthrotomy failure occurred in 50% (8/16) of arthrotomies in the extension group, 6.25% (1/16) in the 30 degrees flexion group and 18.75% (3/16) in the 60 degrees flexion group (P = 0.022). Knee arthrotomy closure in extension compared to flexion had significantly higher rates of failure. PMID- 25134742 TI - Proximal femoral arthroplasty in patients undergoing revision hip arthroplasty. AB - Bone loss represents one of the greatest challenges in revision joint surgery. A retrospective review was conducted of both radiographic and clinical outcomes of eleven patients who underwent revision arthroplasty using a long extensively porous coated cylindrical femoral component. All patients' femurs presented with severe proximal femoral bone loss (Paprosky class IIIB and IV). With a mean follow-up of 8 years (2 to 14) we report no femoral revisions and one acetabular revision to a constrained cup secondary to instability. All patients were clinically and radiographically stable. We did not observe any issue with proximal stress shielding or component loosening. The article reports that in patients with severe proximal femoral bone loss, extensively porous-coated non modular stems are a viable option offering stable and predictable outcomes. PMID- 25134740 TI - The role of family-related factors in the effects of the UP4FUN school-based family-focused intervention targeting screen time in 10- to 12-year-old children: the ENERGY project. AB - BACKGROUND: Screen-related behaviours are highly prevalent in schoolchildren. Considering the adverse health effects and the relation of obesity and screen time in childhood, efforts to affect screen use in children are warranted. Parents have been identified as an important influence on children's screen time and therefore should be involved in prevention programmes. The aim was to examine the mediating role of family-related factors on the effects of the school-based family-focused UP4FUN intervention aimed at screen time in 10- to 12-year-old European children (n child-parent dyads = 1940). METHODS: A randomised controlled trial was conducted to test the six-week UP4FUN intervention in 10- to 12-year old children and one of their parents in five European countries in 2011 (n child parent dyads = 1940). Self-reported data of children were used to assess their TV and computer/game console time per day, and parents reported their physical activity, screen time and family-related factors associated with screen behaviours (availability, permissiveness, monitoring, negotiation, rules, avoiding negative role modeling, and frequency of physically active family excursions). Mediation analyses were performed using multi-level regression analyses (child-school-country). RESULTS: Almost all TV-specific and half of the computer-specific family-related factors were associated with children's screen time. However, the measured family-related factors did not mediate intervention effects on children's TV and computer/game console use, because the intervention was not successful in changing these family-related factors. CONCLUSION: Future screen-related interventions should aim to effectively target the home environment and parents' practices related to children's use of TV and computers to decrease children's screen time. TRIAL REGISTRATION: The study is registered in the International Standard Randomised Controlled Trial Number Register (registration number: ISRCTN34562078). PMID- 25134743 TI - Correlation between knee kinematics and patellofemoral contact pressure in total knee arthroplasty. AB - The aim of this study is to evaluate the relationship between patellofemoral contact stress and intraoperative knee kinematic patterns after mobile bearing total knee arthroplasty (TKA). Medial osteoarthritic knees of forty-six posterior stabilized total knee prostheses were evaluated using a computed tomography guided navigation system. Subjects were divided into two groups based on intraoperative knee kinematic patterns: the medial pivot group (n=19) and the non medial pivot group (n=27). Mean intraoperative patello-femoral contact stress was significantly lower in the medial pivot group than in the non-medial pivot group (1.7MPa vs. 3.2MPa, P<0.05). An intraoperative medial pivot pattern results in reduced patello-femoral contact stress. PMID- 25134739 TI - Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times. AB - Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signaling is exquisitely regulated according to specific phases of cardiac development and that RA signaling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signaling by RA receptors (RARs) in early phases of heart development. This article is part of a Special Issue entitled: Nuclear receptors in animal development. PMID- 25134744 TI - Subtype and regional regulation of prion biomarkers in sporadic Creutzfeldt-Jakob disease. AB - AIMS: Creutzfeldt-Jakob disease (CJD) is a rapid progressive neurological disease leading to dementia and death. Prion biomarkers are altered in the cerebrospinal fluid (CSF) of CJD patients, but the pathogenic mechanisms underlying these alterations are still unknown. The present study examined prion biomarker levels in the brain and CSF of sporadic CJD (sCJD) cases and their correlation with neuropathological lesion profiles. METHODS: The expression levels of 14-3-3, Tau, phospho-Tau and alpha-synuclein were measured in the CSF and brain of sCJD cases in a subtype- and region-specific manner. In addition, the activity of prion biomarker kinases, the expression levels of CJD hallmarks and the most frequent neuropathological sCJD findings were analysed. RESULTS: Prion biomarkers levels were increased in the CSF of sCJD patients; however, correlations between mRNA, total protein and their phosphorylated forms in brain were different. The observed downregulation of the main Tau kinase, GSK3, in sCJD brain samples may help to explain the differential phospho-Tau/Tau ratios between sCJD and other dementias in the CSF. Importantly, CSF biomarkers levels do not necessarily correlate with sCJD neuropathological findings. INTERPRETATION: Present findings indicate that prion biomarkers levels in sCJD tissues and their release into the CSF are differentially regulated following specific modulated responses, and suggest a functional role for these proteins in sCJD pathogenesis. PMID- 25134746 TI - Paralympic sports medicine and sports science--introduction. PMID- 25134745 TI - Typology of sleep medication users and associated mental health and substance use from a Montreal epidemiological study. AB - BACKGROUND: Sleep medication is often reported as one of the most highly used psychotropic drugs in terms of past-year prevalence. Since their use often varies according to the characteristics of individuals, it is important to better understand these particular utilization patterns. OBJECTIVES: The study aims to develop a typology of sleep medication users' characteristics, including their associated mental health and substance use. METHODS: Residents from the epidemiological area of south-west Montreal, Quebec aged 15 years and older responded to a questionnaire in 2009 and 2011. Among the 1822 people who participated at both T1 and T2, 306 (17%) reported use of medication to help them sleep. These participants were selected for cluster analysis based on five variables related to mental health. The identified clusters were then tested for association with sociodemographic, psychosocial, and service use characteristics. RESULTS: A three-cluster solution emerged: 1) older individuals without mental health problems, drug use or psychotropic medication use; 2) individuals with elevated psychological distress, drug use and low social support, and 3) individuals with mood and anxiety disorders, using services for mental health and taking two or more psychotropic medications. CONCLUSIONS: The results establish the significance of problems related to mental health in differentiating sleep medication users. Consideration of these differences may improve the ability of health professionals to provide services that are better suited for patients, including interventions that increase the ability to cope with stress (cluster 2) and more integrated services for those with concurrent disorders (cluster 3). PMID- 25134747 TI - Paralympic classification: conceptual basis, current methods, and research update. AB - Paralympic classification systems aim to promote participation in sport by people with disabilities by controlling for the impact of impairment on the outcome of competition. Valid systems of classification ensure that successful athletes are those who have the most advantageous combination of anthropometric, physiological, and/or psychological attributes, and who have enhanced them to the best effect. Classification systems that are not valid pose a significant threat to Paralympic sport and, therefore, the International Paralympic Committee (IPC) has a Classification Code which includes policy commitment to the development of evidence-based methods of classification. The aim of this article is to provide an overview of current best practice in classification for athletes with physical impairments, and to update research advances in the area. Currently, classification has 4 stages: (1) establish whether the athlete has a health condition that will lead to one or more of the 8 eligible types of physical impairment, (2) determine whether the athlete has an eligible impairment type, (3) determine whether the impairment is severe enough, and (4) determine in what class the athlete should compete. A sequential 4-step process that outlines how to initiate and develop evidence-based methods of classification is described: (1) specification of impairment types that are eligible for the sport; (2) development of valid measures of impairment(s); (3) development of standardized, sport-specific measures of performance; and (4) assessment of the relative strength of association between measures of impairment and measures of performance. Of these, the development and reporting of valid measures of impairment is currently the most pressing scientific challenge in the development of evidence-based methods of classification. PMID- 25134749 TI - Clinical characteristics of 385 illnesses of athletes with impairment reported on the WEB-IISS system during the London 2012 Paralympic Games. AB - BACKGROUND: Prevention of illness is important for a team physician. However, there are few studies that reported clinical aspects of illness of athletes with impairment. OBJECTIVE: To describe the clinical characteristics of the 385 illnesses reported on the a novel Web-based electronic injury and illness capturing system (WEB-IISS) during the London 2012 Paralympic Games. DESIGN: Part of a large prospective cohort study. SETTING: London 2012 Paralympic Games. PARTICIPANTS: Team physicians of 78 delegations (3329 athletes over 14 days) used WEB-IISS. Each day, information was recorded, which included daily team size and illness details, system affected, final diagnosis, type and onset of symptoms, training and/or competition days lost, and suspected cause. MAIN OUTCOME MEASUREMENT: Incidence of illness (illness per 1000 athlete days). RESULTS: The incidence of illness in the cohort was 8.3 per 1000 (95% confidence interval, 7.5 9.1) athlete days, and the percentage of athletes with an illness in this study was 9.2%. Respiratory system illnesses were the most common (39.4%), followed by the digestive system (15.8%), skin and subcutaneous system (11.8%), genitourinary system (8.8%), and nervous system (7.3%). Urinary tract illness was more common in athletes with spinal cord injury (22%) compared with the athletes with other impairments (0%-5%). Skin and subcutaneous illness varied from 0%-18% between impairment categories and was highest for athletes with spinal cord injury. Infections accounted for 40.8% of all illness and 19.5% of illness that resulted in a time loss of >=1 day. In 34% of illnesses, symptoms were present for >=1 day before being reported to the team physician. CONCLUSION: The majority of illnesses affected the respiratory, gastrointestinal, skin and subcutaneous, and genitourinary systems, and were mostly infective in nature. The highest number of all illnesses, including skin and subcutaneous illnesses, and urinary tract illnesses, were of athletes with spinal cord injury. Although most illnesses were not time-loss illnesses, 19.5% of illnesses resulted in >=1 day lost. Team physicians should be aware that, in many cases of infection reported, the symptoms were already present the day before. A delay in reporting of symptoms >24 hours could have important clinical implications for athletes' medical care. PMID- 25134748 TI - Descriptive epidemiology of Paralympic sports injuries. AB - Paralympic sports have seen an exponential increase in participation since 16 patients took part in the first Stoke Mandeville Games on the opening day of the 1948 London Olympic Games. More than 4,000 athletes took part in the London 2012 Paralympic Games. Few sporting events have seen such rapid evolution. This rapid pace of change also has meant challenges for understanding the injury risks of participation, not only because of the variety of sports, impairment types, the evolution of adapted equipment but also because of the inclusion of additional impairment types and development of new sports over time. Early studies were limited in scope but patterns of injuries are slowly emerging within Winter and Summer Paralympic sports. The IPC's London 2012 study is the largest to date with a prospective cohort study involving 49,910 athlete-days. The results identified large differences across sports and highlighted the need for longitudinal sport specific studies rather than solely games-time studies. This will require collaboration with international sports federations to examine injury patterns and risk factors for injury in this population to appropriately inform injury prevention strategies. Further studies will also need to address the impact of sporting participation, injury, and future health. PMID- 25134750 TI - Adaptive sports technology and biomechanics: wheelchairs. AB - Wheelchair sports are an important tool in the rehabilitation of people with severe chronic disabilities and have been a driving force for innovation in technology and practice. In this paper, we will present an overview of the adaptive technology used in Paralympic sports with a special focus on wheeled technology and the impact of design on performance (defined as achieving the greatest level of athletic ability and minimizing the risk of injury). Many advances in manual wheelchairs trace their origins to wheelchair sports. Features of wheelchairs that were used for racing and basketball 25 or more years ago have become integral to the manual wheelchairs that people now use every day; moreover, the current components used on ultralight wheelchairs also have benefitted from technological advances developed for sports wheelchairs. For example, the wheels now used on chairs for daily mobility incorporate many of the components first developed for sports chairs. Also, advances in manufacturing and the availability of aerospace materials have driven current wheelchair design and manufacture. Basic principles of sports wheelchair design are universal across sports and include fit; minimizing weight while maintaining high stiffness; minimizing rolling resistance; and optimizing the sports-specific design of the chair. However, a well-designed and fitted wheelchair is not sufficient for optimal sports performance: the athlete must be well trained, skilled, and use effective biomechanics because wheelchair athletes face some unique biomechanical challenges. PMID- 25134751 TI - From the Paralympics to public health: increasing physical activity through legislative and policy initiatives. AB - Individuals with disabilities experience a disproportionate rate of chronic disease and are more likely to lead sedentary lifestyles than the general population. Multiple complex factors likely contribute to these disparities, including structural, socioeconomic and attitudinal barriers that impede broad participation of individuals with disabilities in health and wellness promotion programs. Public health initiatives aimed at mitigating these health disparities emphasize improved access to physical activity and sports opportunities. Given its visibility, the Paralympic Movement provides an opportunity to transform how society conceptualizes the relationship of disability to physical fitness. The Paralympics also serve as a catalyst for public health education and program development. Already, public policies and governmental regulations are expanding grassroots sports opportunities for youth and adults with disabilities, thus promoting inclusive opportunities for participation in physical activity. PMID- 25134752 TI - Adaptive sports technology and biomechanics: prosthetics. AB - With the technologic advances in medicine and an emphasis on maintaining physical fitness, the population of athletes with impairments is growing. It is incumbent upon health care practitioners to make every effort to inform these individuals of growing and diverse opportunities and to encourage safe exercise and athletic participation through counseling and education. Given the opportunities for participation in sports for persons with a limb deficiency, the demand for new, innovative prosthetic designs is challenging the clinical and technical expertise of the physician and prosthetist. When generating a prosthetic prescription, physicians and prosthetists should consider the needs and preferences of the athlete with limb deficiency, as well as the functional demands of the chosen sporting activity. The intent of this article is to provide information regarding the current advancements in the adaptive sports technology and biomechanics in the field of prosthetics, and to assist clinicians and their patients in facilitating participation in sporting activities. PMID- 25134753 TI - The role of autonomic function on sport performance in athletes with spinal cord injury. AB - Devastating paralysis, autonomic dysfunction, and abnormal cardiovascular control present significant hemodynamic challenges to individuals with spinal cord injury (SCI), especially during exercise. In general, resting arterial pressure after SCI is lower than with able-bodied individuals and is commonly associated with persistent orthostatic intolerance along with transient episodes of life threatening hypertension, known as "autonomic dysreflexia." During exercise, the loss of central and reflexive cardiovascular control attenuates maximal heart rate and impairs blood pressure regulation and blood redistribution, which ultimately reduces venous return, stroke volume, and cardiac output. Thermoregulation also is severely compromised in high-lesion SCI, a problem that is compounded when competing in hot and humid conditions. There is some evidence that enhancing venous return via lower body positive pressure or abdominal binding improves exercise performance, as do cooling strategies. Athletes with SCI also have been documented to self-induce autonomic dysreflexia before competition with a view of increasing blood pressure and improving their performance, a technique known as "boosting." For health safety reasons, boosting is officially banned by the International Paralympics Committee. This article addresses the complex issue of how the autonomic nervous system affects sports performance in athletes with SCI, with a specific focus on the potential debilitating effects of deranged cardiovascular control. PMID- 25134754 TI - Ethical considerations in Paralympic sport: when are elective treatments allowable to improve sports performance? PMID- 25134755 TI - Stories from Sochi: sun, sea, snow, and salt. PMID- 25134757 TI - DNA looping provides for "intersegmental hopping" by proteins: a mechanism for long-range site localization. AB - Studies on how transcription factors and DNA modifying enzymes passively locate specific sites on DNA have yet to be reconciled with a sufficient set of mechanisms that can adequately account for the efficiency and speed of this process. This is especially true when considering that these DNA binding/modifying proteins have diverse levels of both cellular copy numbers and genomic recognition site densities. The monomeric bacterial DNA adenine methyltransferase (Dam) is responsible for the rapid methylation of the entire chromosome (with only ~100 Dam copies per cell) and the regulated methylation of closely spaced sites that controls the expression of virulence genes in several human pathogens. Provocatively, we find that Dam travels between its recognition sites most efficiently when those sites are ~500bp apart. We propose that this is manifested by Dam moving between distal regions on the same DNA molecule, which is mediated by DNA looping, a phenomenon we designate as intersegmental hopping. Importantly, an intermediate found in other systems including two simultaneously bound, looped DNA strands is not involved here. Our results suggest that intersegmental hopping contributes to enzymatic processivity (multiple modifications), which invoke recent reports demonstrating that DNA looping can assist in site finding. Intersegmental hopping is possibly used by other sequence specific DNA binding proteins, such as transcription factors and regulatory proteins, given certain biological context. While a general form of this mechanism is proposed by many research groups, our consideration of DNA looping in the context of processive catalysis provides new mechanistic insights and distinctions. PMID- 25134756 TI - Functional suppression of HAMP domain signaling defects in the E. coli serine chemoreceptor. AB - HAMP domains play key signaling roles in many bacterial receptor proteins. The four-helix HAMP bundle of the homodimeric Escherichia coli serine chemoreceptor (Tsr) interacts with an adjoining four-helix sensory adaptation bundle to regulate the histidine autokinase CheA bound to the cytoplasmic tip of the Tsr molecule. The adaptation helices undergo reversible covalent modifications that tune the stimulus-responsive range of the receptor: unmodified E residues promote kinase-off output, and methylated E residues or Q replacements at modification sites promote kinase-on output. We used mutationally imposed adaptational modification states and cells with various combinations of the sensory adaptation enzymes, CheR and CheB, to characterize the signaling properties of mutant Tsr receptors that had amino acid replacements in packing layer 3 of the HAMP bundle and followed in vivo CheA activity with an assay based on Forster resonance energy transfer. We found that an alanine or a serine replacement at HAMP residue I229 effectively locked Tsr output in a kinase-on state, abrogating chemotactic responses. A second amino acid replacement in the same HAMP packing layer alleviated the I229A and I229S signaling defects. Receptors with the suppressor changes alone mediated chemotaxis in adaptation-proficient cells but exhibited altered sensitivity to serine stimuli. Two of the suppressors (S255E and S255A) shifted Tsr output toward the kinase-off state, but two others (S255G and L256F) shifted output toward a kinase-on state. The alleviation of locked-on defects by on-shifted suppressors implies that Tsr-HAMP has several conformationally distinct kinase-active output states and that HAMP signaling might involve dynamic shifts over a range of bundle conformations. PMID- 25134758 TI - Ryanodine receptors: allosteric ion channel giants. AB - The endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR) form major intracellular Ca(2+) stores. Ryanodine receptors (RyRs) are large tetrameric ion channels in the SR and ER membranes that can release Ca(2+) upon triggering. With molecular masses exceeding 2.2MDa, they represent the pinnacle of ion channel complexity. RyRs have adopted long-range allosteric mechanisms, with pore opening resulting in conformational changes over 200A away. Together with tens of protein and small molecule modulators, RyRs have adopted rich and complex regulatory mechanisms. Structurally related to inositol-1,4,5-trisphosphate receptors (IP3Rs), RyRs have been studied extensively using cryo-electron microscopy (cryo EM). Along with more recent X-ray crystallographic analyses of individual domains, these have resulted in pseudo-atomic models. Over 500 mutations in RyRs have been linked to severe genetic disorders, which underscore their role in the contraction of cardiac and skeletal muscles. Most of these have been linked to gain-of-function phenotypes, resulting in premature or prolonged leak of Ca(2+) in the cytosol. This review outlines our current knowledge on the structure of RyRs at high and low resolutions, their relationship to IP3Rs, an overview of the most commonly studied regulatory mechanisms, and models that relate disease causing mutations to altered channel function. PMID- 25134759 TI - Bezafibrate, a peroxisome proliferator-activated receptor alpha agonist, decreases circulating CD14(+)CD16(+) monocytes in patients with type 2 diabetes. AB - CD14(+)CD16(+) monocytes are proinflammatory cells that produce tumor necrosis factor and interleukin (IL)-1beta. The number of circulating CD14(+)CD16(+) monocytes is increased in patients with chronic renal failure or coronary artery disease. We investigated the effect of bezafibrate, a peroxisome proliferator activated receptor alpha agonist, on circulating CD14(+)CD16(+) monocytes in patients with type 2 diabetes. Using cells isolated from type 2 diabetic subjects, we also examined the in vitro expression of CD16 messenger RNA (mRNA) by mononuclear cells (MNCs) exposed to bezafibrate. The percentage of CD14(+)CD16(+) monocytes among all CD14(+) monocytes was significantly higher in subjects with impaired glucose tolerance (P < 0.01) or type 2 diabetes (P < 0.05) than in those with normal glucose tolerance. The percentage of CD14(+)CD16(+) monocytes was significantly lower in patients with type 2 diabetes who were taking bezafibrate (400 mg/d) than in patients not taking it (P < 0.01). Treatment with bezafibrate for 12 weeks significantly reduced the percentage of circulating CD14(+)CD16(+) monocytes from 45.4 +/- 25.2% to 38.3 +/- 21.8% (P = 0.0144). In an in vitro study, the expression of CD16 mRNA by MNCs from 6 diabetic subjects was decreased after 24 hours of treatment with 10 MUg/mL of bezafibrate (P < 0.05). Expression of IL-1beta mRNA by MNCs was also decreased after 24 hours of treatment with 10 MUg/mL of bezafibrate, whereas the IL-1beta level in the culture supernatant was significantly decreased after treatment of MNCs with either 1 or 10 MUg/mL of bezafibrate. In conclusion, bezafibrate decreased circulating CD14(+)CD16(+) monocytes in patients with type 2 diabetes, probably by inhibiting the expression of CD16 mRNA. PMID- 25134761 TI - Synthesis and Toxicity Evaluation of Some N4-Aryl Substituted 5 Trifluoromethoxyisatin-3-thiosemicarbazones. AB - A series of twenty one N4-aryl substituted 5-trifluoromethoxyisatin-3 thiosemicarbazones 3a-3u was synthesized by the reaction of trifluoromethoxyisatin 1 with different arylthiosemicarbazides 2 in aqueous ethanol (50%), containing a few drops of acetic acid. Their structures were established on the basis of analytical (CHN) and spectral (IR, 1H-NMR, EIMS) data. All the synthesized compounds were evaluated for their toxicity potential by a brine shrimp lethality bioassay. Ten compounds i.e., 3a, 3e, 3i-3l and 3n-3q proved to be active in this assay, displaying promising toxicity (LD50 = 1.11 * 10-5 M - 1.80 * 10-4 M). Amongst these, 3k, 3n and 3o were found to be the most active ones (LD50 = 1.11 * 10-5 M - 1.43 * 10-5 M). Compound 3k showed the highest activity with a LD50 value of 1.11 * 10-5 M and can, therefore, be used as a lead for further studies. Structure-activity relationship (SAR) studies revealed that the presence of strong inductively electron-attracting trifluoromethoxy substituent at position-5 of the isatin moiety played an important role in inducing or enhancing toxic potentiality of some of the synthesized compounds. PMID- 25134763 TI - Recent Advances in the Application of SelectfluorTM F-TEDA-BF4 as a Versatile Mediator or Catalyst in Organic Synthesis. AB - SelectfluorTM F-TEDA-BF4 (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo [2.2.2]octane bis(tetrafluoroborate) is not only one of the most efficient and popular reagents for electrophilic fluorination, but as a strong oxidant is also a convenient mediator or catalyst of several "fluorine-free" functionalizations of organic compounds. Its applications as a mediator in transformations of oxidizable functional groups or gold-catalyzed C-C and C-heteroatom oxidative coupling reactions, a catalyst in formation of various heterocyclic rings, a reagent or catalyst of various functionalizations of electron-rich organic compounds (iodination, bromination, chlorination, nitration, thiocyanation, sulfenylation, alkylation, alkoxylation), a catalyst of one-pot-multi-component coupling reactions, a catalyst of regioselective ring opening of epoxides, a deprotection reagent for various protecting groups, and a mediator for stereoselective rearrangement processes of bicyclic compounds are reviewed and discussed. PMID- 25134760 TI - Evidence that meningeal mast cells can worsen stroke pathology in mice. AB - Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke. PMID- 25134762 TI - Alkylphenol Activity against Candida spp. and Microsporum canis: A Focus on the Antifungal Activity of Thymol, Eugenol and O-Methyl Derivatives. AB - In recent years there has been an increasing search for new antifungal compounds due to the side effects of conventional antifungal drugs and fungal resistance. The aims of this study were to test in vitro the activity of thymol, eugenol, estragole and anethole and some O-methyl-derivatives (methylthymol and methyleugenol) against Candida spp. and Microsporum canis. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC). The minimum fungicidal concentrations (MFC) for both Candida spp. and M. canis were found by subculturing each fungal suspension on potato dextrose agar. Thymol, methylthymol, eugenol, methyl-eugenol, anethole, estragole and griseofulvin respectively, presented the following MIC values against M. canis: 4.8-9.7; 78-150; 39; 78-150; 78-150; 19-39 ug/mL and 0.006-2.5 mg/mL. The MFC values for all compounds ranged from 9.7 to 31 ug/mL. Concerning Candida spp, thymol, methylthymol, eugenol, methyleugenol, anethole, estragole and amphotericin, respectively, showed the following MIC values: 39; 620-1250; 150 620; 310-620; 620; 620-1250 and 0.25-2.0 mg/mL. The MFC values varied from 78 to 2500 ug/mL. All tested compounds thus showed in vitro antifungal activity against Candida spp. and M. canis. Therefore, further studies should be carried out to confirm the usefulness of these alkylphenols in vivo. PMID- 25134764 TI - A New C-3/C-3"-Biflavanone from the Roots of Stellera chamaejasme L. AB - A new 3, 3"-biflavanone, neochamaejasmin C (1), was isolated from the roots of Stellera chamaejasme L., together with four known compounds. Their structures and configurations were elucidated by spectroscopic methods, including 2D-NMR techniques. PMID- 25134765 TI - Quantitative Structure Inter-Activity Relationship (QSInAR). Cytotoxicity Study of Some Hemisynthetic and Isolated Natural Steroids and Precursors on Human Fibrosarcoma Cells HT1080. AB - Combined experimental and quantitative structure inter-activity relationship (QSIAR) computation methods were advanced in order to establish the structural and mechanistic influences that steroids and triterpenes, either as newly synthesized or naturally isolated products, have on human HT1080 mammalian cancer cells. The main Hansch structural indicators such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot) were considered and both the structure-projected as well as globally computed correlations were reported; while the inter-activity correlation of the global activity with those projected on structural information was revealed as equal to the direct structural-activity one for the trial sets of compounds, the prediction for the testing set of molecules reported even superior performances respecting those characteristic for the calibration set, validating therefore the present QSInAR models; accordingly, it follows that the LogP carries the most part of the cytotoxic signal, while POL has little influence on inhibiting tumor growth-A complementary behavior with their earlier known influence on genotoxic carcinogenesis. Regarding the newly hemisynthetic compounds it was found that stigmasta-4,22-dien-3-one is not adapted for cell membrane diffusion; it is recommended that aminocinnamyl chlorohydrate be further modified in order to acquire better steric influence, while aminocinnamyl-2,3,4,6-O-tetraacetyl-alpha-D-glucopyranoside was identified as being inhibited in the tumor cell by other molecular mechanisms-here not revealed-although it has a moderate-high anti-cancer structurally predicted activity. PMID- 25134766 TI - Metabolism study of notoginsenoside R1, ginsenoside Rg1 and ginsenoside Rb1 of radix Panax notoginseng in zebrafish. AB - Zebrafish, a common model organism for studies of vertebrate development and gene function, has been used in pharmaceutical research as a new and powerful tool in recent years. In the present study, we applied zebrafish for the first time in a metabolic study of notoginsenoside (R1), ginsenoside (Rg1) and ginsenoside (Rb1), which are saponins isolated from Panax notoginseng. Metabolites of these three saponin compounds in zebrafish after exposure for 24 h were identified by high performance liquid chromatography - electrospray mass spectrometry (HPLC-ESI-MS) with a Zorbax C-18 column for separation using a binary gradient elution of 0.05% formic acid acetonitrile - 0.05% formic acid water. The quasi-molecular ions of compounds were detected in negative mode. Step-wise deglycosylation metabolites and hydroxylation metabolites of the three saponins were found, which were coincide with regular methods for metabolic analysis. Our study demonstrated that the zebrafish model can successfully imitate the current metabolic model with advantages of lower cost, far less amount of compound needed, easy set up and high performance. Our data suggests that the zebrafish metabolic model has the potential for developing a novel method for quickly predicting the metabolism of Chinese herb components, including those of trace compounds. PMID- 25134767 TI - Enzymatic synthesis of fatty hydroxamic acid derivatives based on palm kernel oil. AB - Fatty hydroxamic acid derivatives were synthesized using Lipozyme TL IM catalyst at biphasic medium as the palm kernel oil was dissolved in hexane and hydroxylamine derivatives were dissolved in water: (1) N-methyl fatty hydroxamic acids (MFHAs); (2) N-isopropyl fatty hydroxamic acids (IPFHAs) and (3) N-benzyl fatty hydroxamic acids (BFHAs) were synthesized by reaction of palm kernel oil and N-methyl hydroxylamine (N-MHA), N-isopropyl hydroxylamine (N-IPHA) and N benzyl hydroxylamine (N-BHA), respectively. Finally, after separation the products were characterized by color testing, elemental analysis, FT-IR and 1H NMR spectroscopy. For achieving the highest conversion percentage of product the optimum molar ratio of reactants was obtained by changing the ratio of reactants while other reaction parameters were kept constant. For synthesis of MFHAs the optimum mol ratio of N-MHA/palm kernel oil = 6/1 and the highest conversion was 77.8%, for synthesis of IPFHAs the optimum mol ratio of N-IPHA/palm kernel oil = 7/1 and the highest conversion was 65.4% and for synthesis of BFHAs the optimum mol ratio of N-BHA/palm kernel oil = 7/1 and the highest conversion was 61.7%. PMID- 25134768 TI - Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids. AB - Six beta-hydroxy-beta-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of this work was to determine anti-inflammatory activity, examine gastric tolerability, and to carry out molecular docking experiments to identify potential COX-2 inhibitors among the beta-hydroxy-beta-aryl propanoic acids, and to elucidate the effect alpha-methyl substitution on the anti-inflammatory activity. Anti-inflammatory activity and gastric tolerability were determined on rats using carrageenan induced paw oedema method, and docking studies were carried out using Autodock v4.0.1. The range of ED50 values is between 127 umol/kg and 15 umol/kg, while the result for ibuprofen is 51.7 umol/kg. Only slight hyperaemia or few petechiae were spotted on rat's stomach. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration, and that 2-methyl-3-hydroxy-3,3-diphenyl-propanoic acid has greatest activity, surpassing that of ibuprofen, a standard NSAID. Another compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of ibuprofen, and is non-chiral and is proven to be non-toxic. The most of investigated compounds have interactions with P3 anchor site like COX-2 selective inhibitors. No tested substances or ibuprofen produced any significant gastric lesions. PMID- 25134769 TI - In Vitro Synergy of Biochanin A and Ciprofloxacin against Clinical Isolates of Staphylococcus aureus. AB - Many clinical isolates of Staphylococcus aureus (S. aureus) are resistant to numerous antimicrobials, including the fluoroquinolones (FQs). Flavonoids such as biochanin A (BCA) are compounds that are naturally present in fruits, vegetables, and plant-derived beverages. The goal of this investigation was to study the possible synergy between the antimicrobial agents BCA and ciprofloxacin (CPFX) when used in combination; CPFX was chosen as a representative FQ compound. We used S. aureus strain ATCC 25923 and 11 fluoroquinolone (FQ)-resistant methicillin-resistant S. aureus (MRSA) strains. Results from the drug susceptibility testing and checkerboard assays show that the minimum inhibitory concentration (MIC) of BCA ranged from 64 ug/mL to 512 ug/mL. When BCA was combined with CPFX, the fractional inhibitory concentration index (FICI) data showed that there was synergy in all 12 of the S. aureus strains tested. No antagonistic activity was observed in any of the strains tested. The results of time-kill tests and agar diffusion tests confirm that there was synergy between BCA and CPFX against S. aureus strains. These results suggest that BCA can be combined with FQs to produce a powerful antimicrobial agent. PMID- 25134770 TI - Green synthesis and antibacterial effect of silver nanoparticles using Vitex negundo L. AB - Different biological methods are gaining recognition for the production of silver nanoparticles (Ag-NPs) due to their multiple applications. One of the most important applications of Ag-NPs is their use as an anti-bacterial agent. The use of plants in the synthesis of nanoparticles emerges as a cost effective and eco friendly approach. In this study the biosynthesis of silver nanoparticles using Vitex negundo L. extract and its antimicrobial properties has been reported. The resulting silver particles are characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD) and UV-Visible (UV-Vis) spectroscopic techniques. The TEM study showed the formation of silver nanoparticles in the 10 30 nm range and average 18.2 nm in size. The XRD study showed that the particles are crystalline in nature, with a face centered cubic (fcc) structure. The silver nanoparticles showed the antimicrobial activity against Gram positive and Gram negative bacteria. Vitex negundo L. was found to display strong potential for the synthesis of silver nanoparticles as antimicrobial agents by rapid reduction of silver ions (Ag+ to Ag0). PMID- 25134771 TI - Fast method for synthesis of alkyl and aryl-N-methylnitrones. AB - A simple, fast, efficient and eco-friendly procedure was developed for the synthesis of alkyl and aryl-N-methylnitrones. The corresponding nitrones of aromatic aldehydes, aliphatic aldehydes and alicyclic carbonyl compounds were prepared from N-methylhydroxylamine hydrochloride and Na2CO3-Na2SO4 by simply grinding at room temperature without using solvent. PMID- 25134772 TI - 3D-QSAR Study of Combretastatin A-4 Analogs Based on Molecular Docking. AB - Combretastatin A-4 (CA-4), its analogues and their excellent antitumoral and antivascular activities, have attracted considerable interest of medicinal chemists. In this article, a docking simulation was used to identify molecules having the same binding mode as the lead compound, and 3D-QSAR models had been built by using CoMFA based on docking. As a result, these studies indicated that the QSAR models were statistically significant with high predictabilities (CoMFA model, q2 = 0.786, r2 = 0.988). Our models may offer help to better comprehend the structure-activity relationships for this class of compounds and also facilitate the design of novel inhibitors with good chemical diversity. PMID- 25134775 TI - Cardanol-based materials as natural precursors for olefin metathesis. AB - Cardanol is a renewable, low cost natural material, widely available as a by product of the cashew industry. It is a mixture of 3-n-pentadecylphenol, 3 (pentadeca-8-enyl)phenol, 3-(pentadeca-8,11-dienyl)phenol and 3-(pentadeca 8,11,14-trienyl)phenol. Olefin metathesis (OM) reaction on cardanol is an important class of reactions that allows for the synthesis of new olefins that are sometime impossible to prepare via other methods. The application of this natural and renewable material to both academic and industrial research will be discussed. PMID- 25134773 TI - Group 11 Metal Compounds with Tripodal Bis(imidazole) Thioether Ligands. Applications as Catalysts in the Oxidation of Alkenes and as Antimicrobial Agents. AB - New group 11 metal complexes have been prepared using the previously described tripodal bis(imidazole) thioether ligand (N-methyl-4,5-diphenyl-2 imidazolyl)2C(OMe)C(CH3)2S(tert-Bu) ({BITOMe,StBu}, 2). The pincer ligand offers a N2S donor atom set that can be used to coordinate the group 11 metals in different oxidation states [AuI, AuIII, AgI, CuI and CuII]. Thus the new compounds [Au{BITOMe,StBu}Cl][AuCl4]2 (3), [Au{BITOMe,StBu}Cl] (4), [Ag{BITOMe,StBu}X] (X = OSO2CF3- 5, PF6- 6) and [Cu{BITOMe,StBu}Cl2] (7) have been synthesized from reaction of 2 with the appropriate metal precursors, and characterized in solution. While attempting characterization in the solid state of 3, single crystals of the neutral dinuclear mixed AuIII-AuI species [Au2{BITOMe,S}Cl3] (8) were obtained and its crystal structure was determined by X-ray diffraction studies. The structure shows a AuIII center coordinated to the pincer ligand through one N and the S atom. The soft AuI center coordinates to the ligand through the same S atom that has lost the tert-butyl group, thus becoming a thiolate ligand. The short distance between the AuI-AuIII atoms (3.383 A) may indicate a weak metal-metal interaction. Complexes 2-7 and the previously described CuI compound [Cu{BITOMe,StBu}]PF6 (9) have been evaluated in the oxidation of biphenyl ethylene with tert-butyl hydrogen peroxide (TBHP) as the oxidant. Results have shown that the AuI and AgI complexes 4 and 6 (at 10 mol % loading) are the more active catalysts in this oxidative cleavage. The antimicrobial activity of compounds 2-5, 7 and 9 against Gram-positive and Gram negative bacteria and yeast has also been evaluated. The new gold and silver compounds display moderate to high antibacterial activity, while the copper derivatives are mostly inactive. The gold and silver complexes were also potent against fungi. Their cytotoxic properties have been analyzed in vitro utilizing HeLa human cervical carcinoma cells. The compounds displayed a very low cytotoxicity on this cell line (5 to 10 times lower than cisplatin) and on normal primary cells derived from C57B6 mouse muscle explants, which may make them promising candidates as potential antimicrobial agents and safer catalysts due to low toxicity in human and other mammalian tissues. PMID- 25134776 TI - Essential Oil Composition of the Different Parts and In Vitro Shoot Culture of Eryngium planum L. AB - The essential oils obtained by hydrodistillation from the different parts (inflorescence, stalk leaves, rosette leaves and root) as well as from in vitro shoot culture of Eryngium planum L. were analyzed by GC-FID-MS in respect to their chemical composition. The different parts of E. planum and in vitro shoots showed different yields. The part with higher amount was the inflorescences, followed by the stalk leaves and in vitro shoots, rosette leaves and finally roots. The essential oils obtained from rosette leaves and in vitro-derived rosettes had totally different composition. Quantitative differences were also found between compounds of intact plant organs. The main components of stalk leaf oil and rosette leaf oil were monoterpene (limonene, alpha- and beta-pinene) and sesquiterpene hydrocarbons. In inflorescence oil cis-chrysanthenyl acetate (43.2%) was accompanied by other esters (propionate, butanoate, hexanoate and octanoate) and numerous oxygenated sesquiterpenes. Root oil and in vitro shoot oil contained mainly (Z)-falcarinol and 2,3,4-trimethylbenzaldehyde. This is the first report on the chemical composition of this species. PMID- 25134774 TI - Proanthocyanidins from Grape Seeds Modulate the NF-kappaB Signal Transduction Pathways in Rats with TNBS-Induced Ulcerative Colitis. AB - To elucidate the molecular mechanisms involved in the therapeutic effects of proanthocyanidins from grape seeds (GSPE), we explore whether GSPE regulates the inflammatory response of TNBS-induced colitis in rats at the levels of NF-kappaB signal transduction pathway. Rats were intragastrically administered of different doses of GSPE (100, 200 and 400 mg.kg-1) per day for seven days after ulcerative colitis (UC) was induced by intracolonic injection of 2,4,6 trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Sulfasalazine (SASP) at 400 mg/kg was used as a positive control drug. The expression of nuclear factor-kappa B (NF-kappaB), phospho-I kappaB-alpha (pIkappaBalpha), inhibitor kappa B kinase (IkappaK) in the colon tissues were all measured by enzyme-linked immunosorbent assay (ELISA) methods. Treatment with GSPE reduced the expression of NF-kappaB, pIkappaBalpha and IkappaK in the colon. The results of this study show that GSPE exerts beneficial effects in inflammatory bowel disease by inhibition of NF-kappaB signal transduction pathways. PMID- 25134777 TI - ESRD from autosomal dominant polycystic kidney disease in the United States, 2001 2010. AB - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is amenable to early detection and specialty care. Thus, while important to patients with the condition, end-stage renal disease (ESRD) from ADPKD also may be an indicator of the overall state of nephrology care. STUDY DESIGN: Retrospective cohort study of temporal trends in ESRD from ADPKD and pre-renal replacement therapy (RRT) nephrologist care, 2001-2010 (n = 23,772). SETTING & PARTICIPANTS: US patients who initiated maintenance RRT from 2001 through 2010 (n = 1,069,343) from US Renal Data System data. PREDICTOR: ESRD from ADPKD versus from other causes for baseline characteristics and clinical outcomes; interval 2001-2005 versus 2006 2010 for comparisons of cohort of patients with ESRD from ADPKD. OUTCOMES: Death, wait-listing for kidney transplant, kidney transplantation. MEASUREMENTS: US census data were used as population denominators. Poisson distribution was used to compute incidence rates (IRs). Incidence ratios were standardized to rates in 2001-2002 for age, sex, and race/ethnicity. Patients with and without ADPKD were matched to compare clinical outcomes. Poisson regression was used to calculate IRs and adjusted HRs for clinical events after inception of RRT. RESULTS: General population incidence ratios in 2009-2010 were unchanged from 2001-2002 (incidence ratio, 1.02). Of patients with ADPKD, 48.1% received more than 12 months of nephrology care before RRT; preemptive transplantation was the initial RRT in 14.3% and fistula was the initial hemodialysis access in 35.8%. During 4.9 years of follow-up, patients with ADPKD were more likely to be listed for transplantation (IR, 11.7 [95% CI, 11.5-12.0] vs 8.4 [95% CI, 8.2-8.7] per 100 person-years) and to undergo transplantation (IR, 9.8 [95% CI, 9.5-10.0] vs 4.8 [95% CI, 4.7-5.0] per 100 person-years) and less likely to die (IR, 5.6 [95% CI, 5.4-5.7] vs 15.5 [95% CI, 15.3-15.8] per 100 person-years) than matched controls without ADPKD. LIMITATIONS: Retrospective nonexperimental registry-based study of associations; cause-and-effect relationships cannot be determined. CONCLUSIONS: Although outcomes on dialysis therapy are better for patients with ADPKD than for those without ADPKD, access to predialysis nephrology care and nondeclining ESRD rates may be a cause for concern. PMID- 25134778 TI - Risk factors for pregnancy outcomes in patients with IgA nephropathy: a matched cohort study. AB - BACKGROUND: The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) are uncertain. This study assessed the effects of pregnancy on kidney disease progression and risk factors for adverse pregnancy outcomes in IgAN. STUDY DESIGN: A matched-cohort study. SETTING & PARTICIPANTS: Women with IgAN with at least one pregnancy, 1 year of follow-up, and kidney function and proteinuria measurement at baseline (time of biopsy) matched with nonpregnant women with IgAN from Peking University First Hospital. PREDICTORS: Pregnancy, treated as a time dependent variable; proteinuria; hypertension; and estimated glomerular filtration rate (eGFR). OUTCOMES: Kidney disease progression, defined as eGFR halving or end-stage kidney disease; rate of eGFR decline; and adverse pregnancy outcomes, including severe pre-eclampsia, intrauterine death, embryo damage, fetal malformation, and induced and spontaneous abortions. RESULTS: Of 239 female patients, 62 women had 69 pregnancies and 62 matched nonpregnant patients were selected as controls. Pregnant patients had median proteinuria at baseline with protein excretion of 1.27 (range, 0.06-7.25)g/d and mean eGFR of 102.3 (range, 40.0-139.0)mL/min/1.73m(2). During a mean follow-up of 45.7 months, 4 patients in the pregnancy group and 6 in the nonpregnancy group had kidney disease progression events. Time-dependent Cox analysis showed that pregnancy was not an independent risk factor for kidney disease progression events (HR, 1.2; 95%CI, 0.3-5.7). There was no significant difference in the median rate of eGFR decline in the 2 groups (-2.5 vs -2.4mL/min/1.73m(2) per year; P=0.7). Adverse pregnancy outcomes were observed in 15 patients. Proteinuria during pregnancy (OR, 1.39; 95%CI, 0.96-2.01) was a borderline predictor of adverse pregnancy outcomes. LIMITATIONS: Retrospective study, most patients had preserved kidney function, study underpowered to detect a difference in kidney failure events. CONCLUSIONS: The study does not permit a definitive conclusion about the effect of pregnancy on kidney disease progression in IgAN. PMID- 25134779 TI - Acute physical activity and delayed attention in primary school students. AB - To examine the influence of different types of exertion on immediate and delayed attention in 116 primary school children divided in three groups of exertion [cognitive exertion - CE (school curricular lesson), physical exertion - PE (traditional physical education lesson), mixed cognitive and physical exertion - CPE (coordinative physical education lesson)]. CPE was the combination of physical load due to the practice of physical exercises and of cognitive load requested to perform movement-based problem solving tasks requiring accurate timing, temporal estimations, temporal production, and spatial adjustments. Children's attentional capacity was tested before (pre) and after (at 0 min and at 50 min post) a CE, a PE, or a CPE lesson, using the d2-test of attention, and analyzed using a 3 * 3 * 2 mixed analysis of covariance with exertion type and time as within factors, gender as between factor, and baseline data as covariate. Effect sizes were calculated as partial eta squared (n(2)). Results showed that participants' attentional performance was significantly affected by exertion type (P < 0.0001), by time (P < 0.0001) and by exertion type * time interactions (P < 0.0001). The effect sizes ranged from medium (0.039) to large (0.437). Varying the type of exertion has different beneficial influences on the level of attention in school children. PMID- 25134780 TI - Where and how to search for information on the effectiveness of public health interventions--a case study for prevention of cardiovascular disease. AB - BACKGROUND: This case study documents the experience of searching for information on the effectiveness of population-level multi-factor interventions for the prevention of cardiovascular disease (CVD) to inform guidance from NICE (National Institute for Health and Care Excellence). OBJECTIVES: To compare suitability of different databases for searches on a medical public health topic and performance of sensitive versus specific strategies. METHODS: A sensitive search strategy identified 34 CVD programmes (reference standard) and sensitivity, precision and number needed to read (NNTR) were compared across seven databases. Two alternative strategies were developed to improve precision while minimising the impact on sensitivity. RESULTS: MEDLINE alone retrieved 91% (31/34) relevant programme citations. Four databases (MEDLINE, CENTRAL, ASSIA and PsycINFO) were required to identify all 34 programmes. In the alternative strategies, greater use of MeSH rather than text and focus on terms directed at population-level interventions resulted in a more precise search on MEDLINE. CONCLUSIONS: MEDLINE alone provided a better yield than anticipated. Additional databases improved sensitivity by 9% but to the detriment of precision. Retrospective searching would provide additional insight into the performance of both databases and strategies. How the medical nature of this public health topic affected yield across databases also requires further investigation. PMID- 25134782 TI - Rs37972 and rs37973 single-nucleotide polymorphisms in the glucocorticoid inducible 1 gene are not associated with asthma risk in a Saudi Arabian population. AB - OBJECTIVE: Rs37972 and rs37973 variants in the glucocorticoid-induced transcript 1 gene have been associated with inhaled glucocorticosteroid responsiveness in asthmatics; however, some discrepancies have been also reported. This study aims to determine whether rs37972 and rs37973 SNPs are associated with asthma risk in Saudi Arabian asthmatics. METHODS: Two-hundred seventy-one diagnosed asthmatics (3-65 years old) and 387 healthy control subjects of equivalent age were recruited. DNA from peripheral blood was purified, and genotyping of rs37972 and rs37973 SNPs was performed by PCR amplification of segments of interest, followed by Sanger sequencing. RESULTS: The global frequencies of the minor (risk) alleles were 28% ("T" allele, rs37972) and 30% ("G" allele, rs37973). Yates-corrected Chi square (chi(2)) tests revealed significant differences between asthmatic and healthy groups, in allele frequencies for rs37973 SNP only (chi(2) = 3.98, Yates' p value = 0.046). Regarding genotype frequencies, a significant difference between asthmatic and healthy groups was observed for variant rs37972 only (chi(2) = 8.19, Yates' p value = 0.016). To determine a possible association of the minor "T" and "G" alleles with asthma, both the recessive and dominant genetic models were tested. For rs37973, none of the genotypes were significantly associated with asthma. Concerning rs37972, the dominant model (C/T + T/T versus C/C) indicated a significant "protective" association with asthma, in which C/T + T/T individuals had lower odds of being asthmatics than C/C individuals (OR = 0.67; 95% CI = 0.48-0.94; p = 0.019*). CONCLUSIONS: The minor alleles "T" and "G" of rs37972 and rs37973 SNPs, respectively, were not significantly associated with increased asthma risk in asthma patients from Saudi Arabia. PMID- 25134781 TI - Associations between central obesity and asthma in children and adolescents: a case-control study. AB - INTRODUCTION: Evidence supports a significant yet weak association between high body weight and asthma in children. However, most studies investigating the obesity-asthma link use Body Mass Index (BMI) to evaluate body fatness. The relationship between body fat distribution and asthma remains largely unknown, especially in children. This pediatric case-control investigation examined associations between central obesity/high-body weight and asthma diagnosis. METHODS: Five-hundred and fourteen children (217 physician diagnosed asthma cases and 297 healthy controls) of 5-11 years were recruited. Height, weight and waist circumference were measured. Asthma symptoms, past medical history, personal lifestyle, socioeconomic status, diet and physical activity history were also collected. RESULTS: A higher proportion of children with asthma were centrally obese [(>=90th waist percentile) 15.2 vs. 9.4%, p<0.0001; (>=90th waist-to-height ratio percentile) 39.6 vs. 24.2%, p<0.0001)]. Regression analyses revealed that centrally obese children were more likely to have asthma (high-waist circumference (OR = 1.99, 95% CI: 1.07-3.68) and high-waist circumference to height ratio (OR = 2.24, 95% CI: 1.47-3.40), following adjustment for various confounders. Overweight/obese participants (BMI defined) were more likely to be asthmatic [odds ratio (OR) = 1.52, 95% confidence interval (CI): 1.03-2.70)] when compared to controls. CONCLUSIONS: Presence of central obesity and high-body weight (at least overweight) as assessed by waist circumference, waist-to-height ratio, and BMI are associated with asthma diagnosis. More studies are needed, especially in children and adolescents, to confirm these findings and better understand how body fat distribution impacts the obesity-asthma relationship. PMID- 25134784 TI - A nested case-control study: personal, social and environmental correlates of vigorous physical activity in adolescents with asthma. AB - OBJECTIVE: Physical activity (PA) is associated with health benefits. Children and adolescents with asthma may be limited in their PA, particularly at vigorous intensity due to asthma symptoms or poor psychological adjustment to asthma. We aimed to investigate if self-perceived competence, enjoyment, support from others and social-physical environment were associated with vigorous physical activity (VPA) and secondarily to assess if such associations were modified by asthma and asthma severity. METHODS: Data from a nested case-control study at 13 years of age within the birth-cohort Environment and Childhood Asthma Study were compiled from 95 participants with and 79 without asthma. The participants completed a questionnaire designed to capture self-perceived competence, enjoyment, support from others and social-physical environment. VPA, defined as >= 6 Metabolic Equivalents, was recorded objectively by SenseWearTM Pro2 Armband. Asthma severity was assessed pragmatically by lung function and use of inhaled glucocorticosteroids and beta2-agonists and incidence of exacerbations in the last 14 days. Data were analysed using linear regression analysis. RESULTS: No significant differences between adolescents with and without asthma were identified in terms of VPA, competence-enjoyment, support from others and social physical environment. Peer support (b = 0.29 (0.05-0.52)) and competence enjoyment (b = 0.23 (0.01-0.44)) were significantly and positively associated with VPA, and teacher support (b = -0.26 (-0.50 to -0.02)) were inversely associated. The model explained 25% of the variance in VPA. CONCLUSIONS: Peer support and competence-enjoyment were positively associated with increased VPN in adolescents irrespectively of asthma and asthma severity. PMID- 25134783 TI - Spirometry effects on conventional and multiple flow exhaled nitric oxide in children. AB - OBJECTIVE: Clinical and research settings often require sequencing multiple respiratory tests in a brief visit. Guidelines recommend measuring the concentration of exhaled nitric oxide (FeNO) before spirometry, but evidence for a spirometry carryover effect on FeNO is mixed. Only one study has investigated spirometry carryover effects on multiple flow FeNO analysis. The objective of this study was to evaluate evidence for carryover effects of recent spirometry on three exhaled NO summary measures: FeNO at 50 ml/s, airway wall NO flux [J'awNO] and alveolar NO concentration [CANO] in a population-based sample of schoolchildren. METHODS: Participants were 1146 children (191 with asthma), ages 12-15, from the Southern California Children's Health Study who performed spirometry and multiple flow FeNO on the same day. Approximately, half the children performed spirometry first. Multiple linear regression was used to estimate differences in exhaled NO summary measures associated with recent spirometry testing, adjusting for potential confounders. RESULTS: In the population-based sample, we found no evidence of spirometry carryover effects. However, for children with asthma, there was a suggestion that exhaled NO summary measures assessed <=6 min after spirometry were lower (FeNO: 25.8% lower, 95% CI: -6.2%, 48.2%; J'awNO: 15.1% lower 95% CI: -26.5%, 43.0%; and CANO 0.43 parts per billion lower, 95% CI: -0.12, 0.98). CONCLUSIONS: In clinical settings, it is prudent to assess multiple flow FeNO before spirometry. In studies of healthy subjects, it may not be necessary to assess FeNO first. PMID- 25134785 TI - Maternal psychological distress mediates the relationship between asthma and physician visits in a population-based sample of adolescents. AB - OBJECTIVE: This study examined whether maternal psychological distress mediates the relationship between presence of adolescent asthma and number of physician visits and whether the association between maternal psychological distress and physician visits is moderated by adolescent general health. METHODS: Data were obtained from the Mater University Study of Pregnancy and included 4025 adolescents. Path analysis was used to examine mediating and moderating effects. RESULTS: Maternal psychological distress was found to partially mediate the relationship between adolescent asthma and number of physician visits, accounting for 25% of the effect of adolescent asthma on physician visits (p = 0.046). There was no evidence to suggest that adolescent general health moderated the association between maternal psychological distress and physician visits (p = 0.093). CONCLUSIONS: These findings suggest that maternal psychological distress is associated with increased physician visits, regardless of adolescents' general health. Lowering maternal psychological distress may serve to reduce health care utilization and costs among adolescents with asthma. PMID- 25134786 TI - Characteristics of postural control among young adults with asthma. AB - OBJECTIVE: We investigated whether young adults with asthma have impaired balance and whether this impairment is related to altered musculoskeletal function and/or psychological characteristics. METHODS: 21 participants with a self-reported asthma diagnosis but no known postural instability or history of falls, and 18 control participants were recruited from undergraduate psychology courses. Participants performed a postural control task of maintaining the center of pressure (COP) in a fixed position with visual feedback (feedback condition) and while standing as still as possible without visual feedback (no-feedback condition). COP variability, regularity and task performance were used to characterize the quality of balance. To document group differences in musculoskeletal function, we measured neck and lower back angles as well as range of motion (ROM) of the neck in the frontal and sagittal planes. To document group differences in psychological state, we administered self-report questionnaires to assess symptoms of anxiety and depression, anxiety sensitivity and negative effect. RESULTS: COP variability and task performance were similar between the groups, but participants with asthma exhibited more regular anterior-posterior COP dynamics. Participants with asthma had smaller ROM of neck extension, a more forwardly bent neck, greater thoracic spine angle, and they reported greater levels of the physical concerns facet of anxiety sensitivity. These musculoskeletal and affective variables moderated COP differences between the groups. CONCLUSIONS: Young adults with asthma showed a different postural control strategy in the absence of any obvious balance impairment. This change in strategy is related to musculoskeletal and affective characteristics of individuals with asthma. PMID- 25134788 TI - Vitamin D counteracts fibrogenic TGF-beta signalling in human hepatic stellate cells both receptor-dependently and independently. AB - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity and constitutes part of the metabolic syndrome, which have been associated with low serum vitamin D (VD). Due to known crosstalk between VD and transforming growth factor (TGF)-beta signalling, VD has been proposed as an antifibrotic treatment. DESIGN: We evaluated the association between VD, the vitamin D receptor (VDR) and liver fibrosis in primary human hepatic stellate cells (phHSC) and 106 morbidly obese patients with NAFLD. RESULTS: Treating phHSC with VD ameliorated TGF-beta-induced fibrogenesis via both VDR-dependent and VDR independent mechanisms. Reduction of fibrogenic response was abolished in cells homozygous for GG at the A1012G single nucleotide polymorphisms within the VDR gene. Compared with healthy livers, NAFLD livers expressed higher levels of VDR mRNA and VDR fragments. VDR mRNA was lower in patients homozygous for GG at A1012G and expression of pro-fibrogenic genes was higher in patients carrying the G allele. CONCLUSIONS: VD may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR may influence the response to VD treatment. PMID- 25134789 TI - Regression analysis of correlated ordinal data using orthogonalized residuals. AB - Semi-parametric regression models for the joint estimation of marginal mean and within-cluster pairwise association parameters are used in a variety of settings for population-averaged modeling of multivariate categorical outcomes. Recently, a formulation of alternating logistic regressions based on orthogonalized, marginal residuals has been introduced for correlated binary data. Unlike the original procedure based on conditional residuals, its covariance estimator is invariant to the ordering of observations within clusters. In this article, the orthogonalized residuals method is extended to model correlated ordinal data with a global odds ratio, and shown in a simulation study to be more efficient and less biased with regards to estimating within-cluster association parameters than an existing extension to ordinal data of alternating logistic regressions based on conditional residuals. Orthogonalized residuals are used to estimate a model for three correlated ordinal outcomes measured repeatedly in a longitudinal clinical trial of an intervention to improve recovery of patients' perception of altered sensation following jaw surgery. PMID- 25134791 TI - Swahili speech development: preliminary normative data from typically developing pre-school children in Tanzania. AB - BACKGROUND: Swahili is widely spoken in East Africa, but to date there are no culturally and linguistically appropriate materials available for speech-language therapists working in the region. The challenges are further exacerbated by the limited research available on the typical acquisition of Swahili phonology. AIM: To describe the speech development of 24 typically developing first language Swahili-speaking children between the ages of 3;0 and 5;11 years in Dar es Salaam, Tanzania. METHODS & PROCEDURES: A cross-sectional design was used with six groups of four children in 6-month age bands. Single-word speech samples were obtained from each child using a set of culturally appropriate pictures designed to elicit all consonants and vowels of Swahili. Each child's speech was audio recorded and phonetically transcribed using International Phonetic Alphabet (IPA) conventions. Children's speech development is described in terms of (1) phonetic inventory, (2) syllable structure inventory, (3) phonological processes and (4) percentage consonants correct (PCC) and percentage vowels correct (PVC). RESULTS & OUTCOMES: Results suggest a gradual progression in the acquisition of speech sounds and syllables between the ages of 3;0 and 5;11 years. Vowel acquisition was completed and most of the consonants acquired by age 3;0. Fricatives/z, s, h/ were later acquired at 4 years and /theta/and /r/ were the last acquired consonants at age 5;11. Older children were able to produce speech sounds more accurately and had fewer phonological processes in their speech than younger children. Common phonological processes included lateralization and sound preference substitutions. CONCLUSIONS & IMPLICATIONS: The study contributes a preliminary set of normative data on speech development of Swahili-speaking children. Findings are discussed in relation to theories of phonological development, and may be used as a basis for further normative studies with larger numbers of children and ultimately the development of a contextually relevant assessment of the phonology of Swahili-speaking children. PMID- 25134792 TI - 13C-engineered carbon quantum dots for in vivo magnetic resonance and fluorescence dual-response. AB - (13)C-engineered carbon quantum dots ((13)C-QDs) were used as magnetic resonance (MR) and fluorescence dual-response probe. The enhanced (13)C-MR signal was observed at 171 ppm from carboxylic and carboxyl carbons in (13)C-QDs with 160 fold improvement on signal-to-noise ratio even when no hyperpolarization was applied, whereas the intrinsic fluorescence of C-QDs was still maintained. The stable MR and fluorescence dual-response was successfully used for long-term observation of zebrafish embryonic development. Cross-validation between MR and fluorescence confirmed the distribution of (13)C-QD in zebrafish. (13)C-MR provides specific information about the presence, magnitude, and progression of (13)C-QDs by defining MR intensity, whereas fluorescence reveals the location of (13)C-QDs with its high sensitivity. (13)C-MR and fluorescence was simultaneously observed within (13)C-QDs, and this work may expand the applications of isotope engineered nanomaterials. PMID- 25134787 TI - A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis. AB - OBJECTIVE: Helper T (Th) cell responses are critical for the pathogenesis of Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th cell subset, but their relevance to H. pylori-induced gastritis is unknown. DESIGN: Flow cytometry, real-time PCR and ELISA analyses were performed to examine cell, protein and transcript levels in gastric samples from patients and mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient and wild-type (control) mice were also examined. Tissue inflammation was determined for pro-inflammatory cell infiltration and pro-inflammatory protein production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC) were isolated, stimulated and/or cultured for Th22 cell function assays. RESULTS: Th22 cells accumulated in gastric mucosa of both patients and mice infected with H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by dendritic cells (DC) during H. pylori infection, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterised by the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22 dependent production of CXCL2 by gastric epithelial cells. Under the influence of IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and S100A9, and suppressed Th1 cell responses, thereby contributing to the development of H. pylori-associated gastritis. CONCLUSIONS: This study, therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22 cells, gastric epithelial cells and MDSCs, which collectively exert a pro inflammatory effect within the gastric microenvironment. Efforts to inhibit this Th22-dependent pathway may therefore prove a valuable strategy in the therapy of H. pylori-associated gastritis. PMID- 25134794 TI - A case of acute glutaraldehyde-induced colitis following polyps treated by EMR. PMID- 25134793 TI - Second harmonic generation microscopy analysis of extracellular matrix changes in human idiopathic pulmonary fibrosis. AB - Patients with idiopathic fibrosis (IPF) have poor long-term survival as there are limited diagnostic/prognostic tools or successful therapies. Remodeling of the extracellular matrix (ECM) has been implicated in IPF progression; however, the structural consequences on the collagen architecture have not received considerable attention. Here, we demonstrate that second harmonic generation (SHG) and multiphoton fluorescence microscopy can quantitatively differentiate normal and IPF human tissues. For SHG analysis, we developed a classifier based on wavelet transforms, principle component analysis, and a K-nearest-neighbor algorithm to classify the specific alterations of the collagen structure observed in IPF tissues. The resulting ROC curves obtained by varying the numbers of principal components and nearest neighbors yielded accuracies of >95%. In contrast, simpler metrics based on SHG intensity and collagen coverage in the image provided little or no discrimination. We also characterized the change in the elastin/collagen balance by simultaneously measuring the elastin autofluorescence and SHG intensities and found that the IPF tissues were less elastic relative to collagen. This is consistent with known mechanical consequences of the disease. Understanding ECM remodeling in IPF via nonlinear optical microscopy may enhance our ability to differentiate patients with rapid and slow progression and, thus, provide better prognostic information. PMID- 25134795 TI - Polycomb protein EED is required for silencing of pluripotency genes upon ESC differentiation. AB - Eed (embryonic ectoderm development) is a core component of the Polycomb Repressive Complex 2 (PRC2) which catalyzes the methylation of histone H3 lysine 27 (H3K27). Trimethylated H3K27 (H3K27me3) can act as a signal for PRC1 recruitment in the process of gene silencing and chromatin condensation. Previous studies with Eed KO ESCs revealed a failure to down-regulate a limited list of pluripotency factors in differentiating ESCs. Our aim was to analyze the consequences of Eed KO for ESC differentiation. To this end we first analyzed ESC differentiation in the absence of Eed and employed in silico data to assess pluripotency gene expression and H3K27me3 patterns. We linked these data to expression analyses of wildtype and Eed KO ESCs. We observed that in wildtype ESCs a subset of pluripotency genes including Oct4, Nanog, Sox2 and Oct4 target genes progressively gain H3K27me3 during differentiation. These genes remain expressed in differentiating Eed KO ESCs. This suggests that the deregulation of a limited set of pluripotency factors impedes ESC differentiation. Global analyses of H3K27me3 and Oct4 ChIP-seq data indicate that in ESCs the binding of Oct4 to promoter regions is not a general predictor for PRC2-mediated silencing during differentiation. However, motif analyses suggest a binding of Oct4 together with Sox2 and Nanog at promoters of genes that are PRC2-dependently silenced during differentiation. In summary, our data further characterize Eed function in ESCs by showing that Eed/PRC2 is essential for the onset of ESC differentiation. PMID- 25134796 TI - Generation of intermediate porcine iPS cells under culture condition favorable for mesenchymal-to-epithelial transition. AB - It has been demonstrated that naive and primed pluripotency are determined by different extracellular signals. In this study, we investigated whether intermediate pluripotent states could be available by manipulating the culture condition during the process of generating pig induced pluripotent stem cells (piPSCs). By optimizing the culture condition that efficiently promotes mesenchymal-to-epithelial transition (MET), we found that combination of three growth factors (LIF, FGF2 and BMP4) and two inhibitors (2i: CHIR99021 and SB431542) could generate an intermediate pluripotent state of piPSCs, which were named as LFB2i-piPSCs. The LFB2i-piPSCs are stable and fulfill all the criteria of pluripotency, including expression of pluripotent genes, differentiation into three germ layers via embryoid bodies in vitro and teratoma in vivo. More importantly, the mRNA-sequencing data showed that LFB2i-piPSCs had a mixed transcriptome of naive and primed pluripotency, which featured by expressing high levels of SOX2, L-MYC and ESRRB and relatively low levels of POU5F1, KLF4 and NANOG. Small RNA sequencing also demonstrated that LFB2i-piPSCs had a mixed microRNA profile of naive and primed pluripotency, which featured by expressing high levels of miR-302b/367 cluster and miR-106a/363 cluster, and low levels of most let-7 family members and miR-17/92 cluster. Altogether, the LFB2i-piPSCs represent a stable intermediate pluripotent state with unique transcriptome and microRNA signatures. The LFB2i-piPSCs will provide a new tool to explore the mechanisms of pluripotency and reprogramming on pig species. PMID- 25134798 TI - Low prospects and high risk: structural determinants of health associated with sexual risk among young African American women residing in resource-poor communities in the south. AB - African American women at increased risk of HIV/sexually transmitted infection (STI) may engage in risky sex as a coping mechanism for depressed economic conditions. This study examines the association between high-risk sexual behavior and structural determinants of sexual health among a sample of young African American women. 237 young African American women (16-19 years old) from economically disadvantaged neighborhoods in North Carolina were enrolled into a randomized trial testing the efficacy of an adapted HIV/STI prevention intervention. Logistic regression analyses predicted the likelihood that young women reporting lack of food at home, homelessness and low future prospects would also report sexual risk behaviors. Young women reporting a lack of food at home (22 %), homelessness (27 %), and low perceived education/employment prospects (19 %) had between 2.2 and 4.7 times the odds as those not reporting these risk factors of reporting multiple sex partners, risky sex partners including older men and partners involved in gangs, substance use prior to sex, and exchange sex. Self-reported structural determinants of sexual health were associated with myriad sexual risk behaviors. Diminished economic conditions among these young women may lead to sexual risk due to hopelessness, the need for survival or other factors. PMID- 25134797 TI - Construction of corneal epithelium with human amniotic epithelial cells and repair of limbal deficiency in rabbit models. AB - This study aims to evaluate the effect of a human amniotic epithelial cell (HAEC) rabbit corneal stroma tissue-engineered cornea on ocular reconstruction in three different animal models. HAECs were isolated from human placenta, seeded onto rabbit corneal stroma. HAECs-rabbit corneal stroma tissue engineering cornea transplantation was examined in three distinct rabbit models: transplantation of cornea constructed (1) with lamellar corneal HAECs and rabbit corneal stroma, (2) with central corneal HAECs and rabbit corneal stroma, or (3) with full-thickness corneal HAECs and rabbit corneal stroma. In the tissue engineering corneal transplantation groups in all three models, the mean number of days to corneal epithelial healing was significantly shorter than that in the control group and the mean number of days to corneal neovascularization was significantly greater than in the control group. In addition, in the tissue engineering corneal transplantation groups in the central lamellar cornea model and the full thickness corneal transplantation model neovascularization, corneal turbidity, and epithelial fluorescence were significantly less than in the control groups. HAECs can be induced to differentiate into corneal epithelial cells, which may be suitable for the reconstruction of the corneal epithelium in cases of limbal stem cell deficiency. PMID- 25134801 TI - Evaluation of (68)Ga-DOTANOC PET/CT imaging in a large exclusive population of pancreatic neuroendocrine tumors. AB - PURPOSE: To evaluate the diagnostic accuracy of (68)Ga-DOTANOC PET/CT imaging in a large exclusive population of pancreatic neuroendocrine tumors (NETs). METHODS: Data of 141 (mean age 46.2 +/- 15.2 years) patients who underwent 178 (68)Ga DOTANOC PET/CT studies for diagnosis/staging (n = 88) and restaging (n = 90) of pancreatic NET were retrospectively analyzed. PET/CT results were compared to conventional imaging (CIM) when available (n = 86). Histopathology and/or clinical/imaging follow-up (minimum 6 months) were used as reference standard. RESULTS: The overall sensitivity, specificity, and accuracy of (68)Ga-DOTANOC PET/CT were 85.7%, 79.1%, and 84.8%. The corresponding values were 73%, 50%, and 70.4% for diagnosis/staging groups and 98.6%, 100%, and 98.8% for restaging groups. The accuracy was significantly higher for restaging as compared to diagnosis/staging (P < 0.0001) and in non-insulinoma tumors than insulinomas (P < 0.0001). The SUVmax of primary tumors was significantly higher than metastatic lesions overall (P = 0.001), as well as in diagnosis/staging (P = 0.041) and restaging (P = 0.0003) subgroups. When available, CIM was less specific than (68)Ga-DOTANOC PET/CT (P < 0.001) and showed fewer lesions. CONCLUSIONS: (68)Ga DOTANOC PET/CT is useful for diagnosis/staging and restaging of patients with pancreatic NET. It demonstrates more lesions compared to CIM and is more specific. PMID- 25134799 TI - The roles of troponin C isoforms in the mechanical function of Drosophila indirect flight muscle. AB - Stretch activation (SA) is a fundamental property of all muscle types that increases power output and efficiency, yet its mechanism is unknown. Recently, studies have implicated troponin isoforms as important in the SA mechanism. The highly stretch-activated Drosophila IFMs express two isoforms of the Ca(2+) binding subunit of troponin (TnC). TnC1 (TnC-F2 in Lethocerus IFM) has two calcium binding sites, while an unusual isoform, TnC4 (TnC-F1 in Lethocerus IFM), has only one binding site. We investigated the roles of these two TnC isoforms in Drosophila IFM by targeting RNAi to each isoform. IFMs with TnC4 expression (normally ~90% of total TnC) replaced by TnC1 did not generate isometric tension, power or display SA. However, TnC4 knockdown resulted in sarcomere ultrastructure disarray, which could explain the lack of mechanical function and thus make interpretation of the influence of TnC4 on SA difficult. Elimination of TnC1 expression (normally ~10% of total TnC) by RNAi resulted in normal muscle structure. In these IFMs, fiber power generation, isometric tension, stretch activated force and calcium sensitivity were statistically identical to wild type. When TnC1 RNAi was driven by an IFM specific driver, there was no decrease in flight ability or wing beat frequency, which supports our mechanical findings suggesting that TnC1 is not essential for the mechanical function of Drosophila IFM. This finding contrasts with previous work in Lethocerus IFM showing TnC1 is essential for maximum isometric force generation. We propose that differences in TnC1 function in Lethocerus and Drosophila contribute to the ~40-fold difference in IFM isometric tension generated between these species. PMID- 25134800 TI - Relationship of bone mineralization density distribution (BMDD) in cortical and cancellous bone within the iliac crest of healthy premenopausal women. AB - Bone mineralization density distribution (BMDD) is an important determinant of bone mechanical properties. The most available skeletal site for access to the BMDD is the iliac crest. Compared to cancellous bone much less information on BMDD is available for cortical bone. Hence, we analyzed complete transiliac crest bone biopsy samples from premenopausal women (n = 73) aged 25-48 years, clinically classified as healthy, by quantitative backscattered electron imaging for cortical (Ct.) and cancellous (Cn.) BMDD. The Ct.BMDD was characterized by the arithmetic mean of the BMDD of the cortical plates. We found correlations between Ct. and Cn. BMDD variables with correlation coefficients r between 0.42 and 0.73 (all p < 0.001). Additionally to this synchronous behavior of cortical and cancellous compartments, we found that the heterogeneity of mineralization densities (Ct.Ca(Width)), as well as the cortical porosity (Ct.Po) was larger for a lower average degree of mineralization (Ct.Ca(Mean)). Moreover, Ct.Po correlated negatively with the percentage of highly mineralized bone areas (Ct.Ca(High)) and positively with the percentage of lowly mineralized bone areas (Ct.Ca(Low)). In conclusion, the correlation of cortical with cancellous BMDD in the iliac crest of the study cohort suggests coordinated regulation of bone turnover between both bone compartments. Only in a few cases, there was a difference in the degree of mineralization of >1wt % between both cortices suggesting a possible modeling situation. This normative dataset of healthy premenopausal women will provide a reference standard by which disease- and treatment-specific effects can be assessed at the level of cortical bone BMDD. PMID- 25134802 TI - Radiological diagnosis and management of idiopathic spontaneous intra-abdominal haemorrhage (abdominal apoplexy): a case series. AB - PURPOSE: Idiopathic spontaneous intraperitoneal haemorrhage (ISIH), historically known as abdominal apoplexy, is spontaneous haemorrhage due to rupture of an intra-abdominal visceral vessel in the absence of trauma or underlying pathology. It is an exceptionally rare condition, with mostly scattered case reports available. The aim of this study was to describe this rare condition, possible associated risk factors, and usefulness of multislice-CT (MS-CT) angiogram in its diagnosis prior to intervention. METHODS: A retrospective review of patients diagnosed with ISIH. Radiological records of haemoperitoneum from a single tertiary hospital in 2006-2013 were analysed, and the cases of ISIH were identified. Demographics (including pre-morbid hypertension status), abdominal aortic calcification as a measure of atherosclerotic changes, MS-CT angiogram +/- conventional digital subtraction angiograph images, surgical records and outcomes were reviewed. RESULTS: 425 cases of haemoperitoneum were retrieved from hospital radiology database from 2006 to 2013, and 5 patients (1.1%) diagnosed with ISIH were identified (4 males, 1 female, mean age of 64 years). 4 out of 5 patients (80%) had a history of hypertension (mean 150/90 mmHg) and 3 patients had moderate abdominal aortic atherosclerosis. MS-CT angiogram was able to diagnose the bleeding source in 4 out of 5 patients, while the bleeding source remained occult in the last patient even with both MS-CT and traditional DSA angiography. Patients who underwent either embolization or surgery had no further re-bleeding in clinical follow up, ranging from 5 to 8 years. CONCLUSIONS: Hypertension and abdominal aortic atherosclerosis appear to be associated risk factors for ISIH, and MS-CT angiogram has a high sensitivity in detecting the site of haemorrhage. An integrated angiographic and surgical approach is important in managing patients with ISIH. PMID- 25134803 TI - Does abdominal pain duration affect the accuracy of first-line MRI for pediatric appendicitis? AB - PURPOSE: To compare the accuracy of first-line MRI for pediatric appendicitis between children with different durations of abdominal pain. MATERIALS AND METHODS: Between November 2012 and September 2013, 364 pediatric patients underwent MRI for clinically suspected appendicitis. Patients were stratified into one group with pain lasting less than or equal to 1 day and pain longer than 1 day. RESULTS: In patients with early abdominal pain, appendicitis occurred in 83 of 208 patients (39.9%) vs. 49 of 156 patients with pain longer than 1 day (31.4%, p = 0.09). Sensitivity and specificity of MRI in patients with early abdominal pain were 97.6% (95% CI [91.6%-99.3%]) and 94.4% (95% CI [88.9% 97.3%]), respectively, vs. 93.9% (95% CI [83.5%-97.9%]) and 97.2% (95% CI [92.1% 99.4%]), respectively, in patients with pain longer than 1 day in duration (p = 0.36 and p = 0.35 for sensitivity and specificity, respectively). CONCLUSIONS: First-line MRI is accurate for acute appendicitis in children presenting with early abdominal pain, and may be appropriate as the initial examination in children. Further prospective studies are needed to compare MRI vs. ultrasound as the initial examination in children with early abdominal pain to help further delineate a diagnostic imaging algorithm. PMID- 25134804 TI - Gly322Asp and Asn127Ser single nucleotide polymorphisms (SNPs) of hMSH2 mismatch repair gene and the risk of triple-negative breast cancer in Polish women. AB - Triple-negative breast cancer (TNBC) is characterised by worse clinical outcome and poor prognosis. The alterations in the oncogenes and tumor suppressor genes as well as microsatellite instability (MSI) have been associated with breast cancer development. It is knowledge that the most common mechanism inducing MSI in many cancer is genomic rearrangements found in the hMSH2 (human MutS homolog 2) gene. In this report we genotyped two polymorphisms of hMSH2 DNA repair gene in 70 TNBC patients and 70 age-matched cancer-free women using RFLP-PCR. The following polymorphisms were studied: an A/G transition at 127 positions producing an Asn/Ser substitution at codon 127 (the Asn127Ser polymorphism, rs17217772) and a G/A transition at 1032 position resulting in a Gly/Asp change at codon 322 (the Gly322Asp polymorphism, rs4987188). We found an association between the hMSH2 Asp/Asp and Gly/Asp genotypes and TNBC occurence. Variant Asp allele of hMSH2 decreased cancer risk [odds ratio (OR) 0.11; 95 % confidence interval (CI) 0.05-0.21]. The risk of TNBC in the carriers of the Gly322Gly Asn127Ser combined genotype was increased (OR 3.71; 95 % CI 1.36-10.10). However the risk of TNBC was not alter by polymorphism Asn127Ser of the hMSH2 gene. The Gly322Asp polymorphism of the hMSH2 gene may be linked with TNBC occurrence in Polish women. PMID- 25134805 TI - Genetic and demographic bottleneck analysis of Indian camel breeds by microsatellite markers. AB - The genetic and demographic bottleneck analysis of Indian camel breeds was carried out utilizing 40 microsatellite markers. Allelic polymorphism was observed at 20 loci in the Indian dromedary breeds. A total of 66 alleles were scored. The average number of alleles, expected heterozygosity and polymorphic information content were, respectively, 3.25 +/- 0.27, 0.56 +/- 0.04 and 0.49 +/- 0.04 in Bikaneri; 3.25 +/- 0.25, 0.53 +/- 0.03 and 0.46 +/- 0.03 in Jaisalmeri; 3.0 +/- 0.21, 0.53 +/- 0.04 and 0.45 +/- 0.03 in Kachchhi and 3.1 +/- 0.19, 0.51 +/- 0.03 and 0.44 +/- 0.03 in Mewari breed. Higher genetic variation was observed in most numerous Bikaneri breed. Genetic distances were least between the breed pair Bikaneri and Jaisalmeri which was closely placed with the Kachchhi breed. The Mewari camels had relatively higher genetic distance from the other three Indian dromedary breeds. The bottleneck analysis revealed the presence of genetic bottleneck in all four breeds of Indian dromedary. However, the qualitative graphical method resulted in normal L-shaped distribution of allele frequencies in Jaisalmeri breeds and shifted mode in Bikaneri, Kachchhi and Mewari breeds. The demographic bottleneck analysis revealed minimum reduction (-9.65 %) in the population of camels in Jaisalmeri breeding tract as compared to that of Bikaneri (-14.18 %), Kachchhi (-27.78 %) and Mewari (-32 %) breeding tracts. Conclusively, the genetic bottleneck analysis could explain the demographic bottleneck in the Indian dromedary populations. Therefore, appropriate conservation and improvement efforts are needed in all four dromedary breeds with immediate attention on Mewari and Kachchhi breeds. The present study is the first report in demonstrating the genetic basis of demographic bottleneck in the Indian dromedary populations. PMID- 25134806 TI - Short-wave solar radiation level willingly tolerated by lactating Holstein cows in an equatorial semi-arid environment. AB - The amount of short-wave solar radiation willingly tolerated by lactating Holstein cows on pasture was determined in an equatorial semi-arid environment. The study was carried out on a dairy farm located in Limoeiro do Norte, CE, northeastern Brazil. The observed behaviours were as follows: grazing, under the sun, under the shade, standing, lying, ruminating, idling and wallowing in the water. The behaviours were recorded using instantaneous scan sampling at regular intervals of 15 min from 0600 to 1800 hours over 5 days. On all sampling days, the meteorological variables, including local short-wave solar radiation (R S-W, W m(-2)), were recorded. The R S-W data were divided into five levels. The sun exposure was more frequent under low (100 %) and moderately low (97 %) levels, when R S-W remained below 500 W m(-2). The grazing was more intense under low (100 %) and moderately low (93 %) levels. Above 500 W m(-2), the grazing time significantly decreased (11 %). The cows avoided grazing under high (0 %) and very high (0 %) levels, when R S-W exceeded 700 W m(-2). The ruminating behaviour was more frequent under high (33 %) and very high (37 %) levels, in which the highest averages of R S-W were recorded (815 and 958 W m(-2), respectively). The standing posture was more frequent under low (100 %) and moderately low (97 %) levels. Therefore, the critical R S-W level that motivates cows to stop grazing and seek shade was in the interval between 500 and 700 W m(-2). PMID- 25134808 TI - Single-Tablet Regimens in HIV Therapy. AB - Combined antiretroviral therapy (cART) has evolved considerably over the past decades leading to a better control of human immunodeficiency virus replication. Recently, regimens have evolved so as to simplify dosing frequency and reduce pill burden to improve adherence. Several national and international guidelines suggest antiretroviral (ARV) regimen simplification as a method of improving adherence. Decreased cART adherence has been associated with both patient-related factors and regimen-related factors. Adherence rates are statistically higher when simpler, once-daily (OD) regimens are combined with smaller daily regimen pill burdens. The avoidance of selective non-adherence, where a patient takes part of a regimen but not the full regimen, is a further potential benefit offered by single-tablet regimens (STRs). Simplification of cART has been associated with a better quality of life (QoL). Although tempered by other factors, better adherence, higher QoL and patients' preferences are all key points which might combine to assure long-lasting efficacy and durability of cART. All studies underlined the favorable tolerability profile of newer STRs. Three STRs are currently available. Tenofovir (TDF) plus emtricitabine (FTC)/efavirenz (EFV) was the first OD complete ARV regimen available as a STR. TDF plus FTC/rilpivirine is a second-generation STR. The most recently approved STR, TDF plus FTC/cobicistat/elvitegravir, is the first non-nucleoside reverse transcriptase inhibitor-based STR. All of them have shown excellent efficacy; safety and tolerability have been improved by more recent formulations. Several other STRs are anticipated both combining completely different drugs, abacavir (ABC) plus lamivudine (3TC)/dolutegravir, utilizing innovative formulations of older drugs, tenofovir alafenamide fumarate, or taking advance of bioequivalent drugs, lamivudine (3TC) plus ABC/EFV. The future challenge would be to develop completely alternative STRs (including for example protease inhibitors or new molecules) to extend the advantages of simplicity to heavily pre-treated individuals. PMID- 25134809 TI - Epidemiology of pneumococcal disease in a national cohort of older adults. AB - INTRODUCTION: Streptococcus pneumoniae is a major cause of morbidity and mortality. We sought to describe the epidemiology of non-invasive and invasive pneumococcal disease in a national Veterans Affairs population within the United States. METHODS: We conducted a retrospective study in older patients (aged >=50 years) with positive pneumococcal cultures from any site between 2002 and 2011. We described outpatient and inpatient pneumococcal disease incidence per 100,000 clinic visits/hospitalizations. Repeat cultures within a 30-day period were considered to represent the same episode. To describe the epidemiology of serious pneumococcal infections (bacteremia, meningitis, pneumonia), we assessed demographics, clinical characteristics, and risk factors for S. pneumoniae. Pneumonia was defined as a positive respiratory culture with a pneumonia diagnosis code. Bacteremia and meningitis were identified from positive cultures. Generalized linear mixed models were used to quantify changes over time. RESULTS: Over the study period, we identified 45,983 unique episodes of pneumococcal disease (defined by positive cultures). Incidence decreased significantly by 3.5% per year in outpatients and increased non-significantly by 0.2% per year in inpatients. In 2011, the outpatient and inpatient incidence was 2.6 and 328.1 infections per 100,000 clinic visits/hospitalizations, respectively. Among inpatients with serious infections, chronic disease risk factors for pneumococcal disease increased significantly each year, including respiratory disease (1.9% annually), diabetes (1.3%), and renal failure (1.0%). Overall, 30.2% of inpatients with serious infections had a pneumococcal immunization in the previous 5 years. Invasive disease (37.4% versus 34.9%, P = 0.004) and mortality (14.0% versus 12.7%, P = 0.045) were higher in non-vaccinated patients compared to vaccinated patients. CONCLUSIONS: In our national study of older adults, the baseline health status of those with serious pneumococcal infections worsened over the study period. As the population ages and the chronic disease epidemic grows, the burden of pneumococcal disease is likely to increase thus highlighting the importance of pneumococcal vaccination. PMID- 25134811 TI - Impact of a Multidisciplinary Culture Follow-up Program of Antimicrobial Therapy in the Emergency Department. AB - INTRODUCTION: Antimicrobial prescribing in the emergency department is predominantly empiric, with final microbiology results either unavailable or reported after most patients are discharged home. Systematic follow-up processes are needed to ensure appropriate antimicrobial therapy at this transition of care. The objective of this study was to assess the impact of a culture follow-up (CFU) program on the frequency of emergency department (ED) revisits within 72 h and hospital admissions within 30 days compared to the historical standard of care (SOC). Additionally, infection characteristics and antimicrobial therapy were compared. METHODS: A single group, pre-test post-test quasi-experimental study was conducted comparing a retrospective SOC group to a prospective CFU group. CFU was implemented using computerized decision-support software and a multidisciplinary team of pharmacists and emergency physician staff. RESULTS: Over the four-month intervention period the CFU group evaluated 197 cultures and modified antimicrobial therapy in 25.5%. The rate of combined ED revisits within 72 h and hospital admissions within 30 days was 16.9% in the SOC group and 10.2% in the CFU group (p = 0.079). When evaluating the uninsured population alone, revisits to the ED within 72 h were reduced from 15.3% in the SOC group to 2.4% in the CFU group (p = 0.044). CONCLUSION: Implementation of a multidisciplinary CFU program was associated with a reduction in ED revisits within 72 h and hospital admissions within 30 days. One-fourth of patients required post discharge intervention, representing a large need for antimicrobial stewardship expansion to ED practice models. PMID- 25134810 TI - Observation of "seesaw effect" with vancomycin, teicoplanin, daptomycin and ceftaroline in 150 unique MRSA strains. AB - INTRODUCTION: Vancomycin (VAN) failures associated with the treatment of complicated methicillin-resistant Staphylococcus aureus (MRSA) infections have been well described. The reported "seesaw effect" demonstrates improved beta lactam activity when VAN and/or daptomycin (DAP) susceptibility decreases. However, there are minimal data comparing ceftaroline (CPT) susceptibility with these agents or teicoplanin (TEI). Therefore, to further explore the seesaw effect, we evaluated the relationship between CPT and VAN, TEI, and DAP susceptibilities. METHODS: One hundred and fifty clinical MRSA isolates from the Anti-Infective Research Laboratory (Detroit, MI, USA) from 2008 to 2012 were analyzed. VAN, TEI, DAP and CPT minimum inhibitory concentrations (MIC) were determined via Etest methodology. MIC50 and MIC90 were calculated for each antibiotic. Additionally, four isogenic strain pairs were randomly selected for evaluation by time-kill methodology for the potential of enhanced killing by CPT as MICs increased to VAN, TEI, and DAP. RESULTS: CPT MICs were inversely correlated with VAN, DAP, and TEI MICs with correlation coefficients of -0.535, 0.483, and -0.386, respectively (P <= 0.05). Comparison of the MIC relationship for glycopeptides and lipopeptides resulted in a positive correlation for all agent combinations. In time-kill evaluations, CPT demonstrated greater reductions in log10 colony-forming unit (CFU)/mL against mutant strains (3.73 +/- 0.67) versus parents (2.79 +/- 0.75) despite no change in CPT MIC (P = 0.112). CONCLUSION: This study demonstrated a marked "seesaw effect" whereby CPT displayed increased susceptibility as the VAN, DAP, and TEI MICs increased. Additionally, we observed a positive linear correlation between VAN, DAP, and TEI MICs for all agent combinations. Enhanced activity was noted with CPT in mutant strains versus the parent strains despite no change in MIC. Based upon the enhanced CPT activity observed against strains with decreased susceptibility to VAN, DAP and TEI, CPT may provide an option for infections with reduced susceptibility to glycopeptides or lipopeptides. Further evaluation is warranted to investigate the clinical implications of the seesaw effect. PMID- 25134812 TI - Lack of Change in Susceptibility of Pseudomonas aeruginosa in a Pediatric Hospital Despite Marked Changes in Antibiotic Utilization. AB - INTRODUCTION: It is assumed that a direct relationship exists between the extent of use of any given antibiotic or antibiotic class and the degree of susceptibility or resistance on the part of various bacteria to that antibiotic or class. METHODS: Pseudomonas aeruginosa susceptibility rates and utilization of key antipseudomonal antibiotics in a pediatric hospital, reflected as grams/1,000 patient days, were studied over a 7-year period. RESULTS: While the volume of use of a number of antibiotics changed dramatically over this time period, susceptibility of Pseudomonas to these same agents remained relatively stable. The use of aminoglycosides decreased 14.5% while that of piperacillin/tazobactam increased 92% over the period of observation while susceptibility generally varied by <10%. CONCLUSION: Contrary to popular belief, changes in antibiotic utilization patterns do not always result in changes in susceptibility thus emphasizing the importance of continual institutional monitoring of antibiotic use and susceptibility patterns. PMID- 25134813 TI - Erratum to: Epidemiology of Pneumococcal Disease in a National Cohort of Older Adults. PMID- 25134815 TI - NMR and molecular dynamics study of the size, shape, and composition of reverse micelles in a cetyltrimethylammonium bromide (CTAB)/n-hexane/pentanol/water microemulsion. AB - The size, shape, and composition of reverse micelles (RMs) in a cetyltrimethylammonium bromide (CTAB)/pentanol/n-hexane/water microemulsion were investigated using pulsed gradient stimulated echo (PGSTE) nuclear magnetic resonance (NMR) measurements and molecular modeling. PGSTE data were collected at observation times (Delta) of 10, 40, and 450 ms. At long observation times, CTAB and pentanol exhibited single diffusion coefficients. However, at short (Delta <= 40 ms) observation times both CTAB and pentanol exhibited slow and fast diffusion coefficients. These NMR data indicate that both CTAB and pentanol molecules reside in different environments within the microemulsion and that there is exchange between regions on the millisecond time scale. Molecular dynamic simulations of the CTAB RM, in a solvent box containing n-hexane and pentanol, produced an ellipsoid shaped RM. Using structural parameters from these simulations and the Stokes-Einstein relation, the structure factor and dimensions of the reverse micelle were determined. Analysis of the composition of the interphase also showed that there was a variation in the ratio of surfactant to cosurfactant molecules depending on the curvature of the interphase. PMID- 25134816 TI - Interobserver and intraobserver reliability of the radiographic analysis of femoroacetabular impingement and dysplasia using computer-assisted measurements. AB - BACKGROUND: A comprehensive evaluation of hip radiographs in the young adult with hip pain has become increasingly complex and time consuming. The interobserver reliability of manually performed measurements of femoroacetabular impingement, including the alpha angle, has been questioned. Methods to improve the reliability of a radiographic evaluation may increase the clinical utility of these parameters. PURPOSE: To determine the interobserver and intraobserver reliability of a computer-assisted radiographic analysis of the young adult hip in a clinically relevant setting. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: A reliability study of a comprehensive computer-assisted radiographic evaluation was performed, which included 25 radiographic parameters of proximal femoral morphology, acetabular morphology, hip osteoarthritis, and pelvic tilt/rotation. Anteroposterior pelvis and 45 degrees Dunn lateral radiographs of 70 consecutive patients undergoing hip preservation surgery were included. Each radiograph was analyzed by 4 experienced hip surgeons. The reliability of continuous measurements was analyzed using intraclass correlation coefficients (ICCs), while categorical parameters were analyzed using kappa values and percentages of agreement. RESULTS: The interobserver reliability of the parameters of proximal femoral morphology, acetabular morphology, and osteoarthritis was generally substantial to excellent. Parameters with lesser interobserver reliability included the alpha angle (ICC, 0.43), Tonnis osteoarthritis classification (kappa = 0.22), and classification of pelvic tilt (using the coccyx or sacrococcygeal joint) (kappa = 0.43 and 0.61, respectively). CONCLUSION: A computer-assisted analysis of young adult hip radiographs generally demonstrates substantial to excellent levels of interobserver reliability for most parameters. However, alpha angle measurements demonstrated only moderate interobserver reliability, despite excellent intraobserver reliability. Measurements of the joint space width appear to be significantly more reliable than the use of the Tonnis osteoarthritis classification in this population. The classification of pelvic tilt utilizing the coccyx or sacrococcygeal joint is only moderately reliable. PMID- 25134817 TI - Concentration-dependent effects of spermine on apoptosis and consequent generation of multilayer myotube sheets from mouse embryoid bodies in vitro. AB - The concentration-dependent effect of spermine was investigated on the spermine induced generation of multilayer myotube sheets (MMTS) from mouse embryoid bodies (EBs). During spermine treatment for 24 h, a monolayer cell sheet that had already grown radially from the periphery of an EB was exfoliated. The exfoliation was inhibited by z-VAD.fmk, indicating the occurrence of apoptosis, and inhibited also by aminoguanidine, indicating the involvement of amine oxidase. Following the exfoliation, the cell growth restarted from the fresh periphery of EB in a spermine-free medium and finally formed MMTS. To analyze the contribution of apoptosis to the cell death causing exfoliation, the numbers of apoptotic, necrotic, and 2nd apoptotic cells were counted by staining with Annexin V-Cyanine-3 (AVC3) and 7-aminoactinomycin (7AAC). AVC3-positive, 7AAC positive, and AVC3/7AAC doubly positive cells were assigned as apoptotic, necrotic, and 2nd necrotic cells, respectively. The relative number of apoptotic and 2nd necrotic cells (N A + N A/7) to the total number of dying cells (N T) was 84 ~ 94%, which was independent of spermine concentration in the range from 0.1 to 2.0 mM. The MMTS generation rate at the final stage, however, was dependent on the spermine concentration. It was 60 ~ 80% in the range from 0.1 to 1.5 mM, while it decreased sharply to 1% at 2 mM. This suggests another role of spermine in the MMTS generation in addition to the induction of apoptosis. This 2nd role seems to be inhibited at a spermine concentration higher than a critical limit between 1.5 and 2.0 mM. PMID- 25134818 TI - The expression of pluripotency genes and neuronal markers after neurodifferentiation in fibroblasts co-cultured with human umbilical cord blood mononuclear cells. AB - Human umbilical cord blood is an attractive source of stem cells; however, it has a heterogeneous cell population with few mesenchymal stem cells. Cell reprogramming induced by different methodologies can confer pluripotency to differentiated adult cells. The objective of this study was to evaluate the reprogramming of fibroblasts and their subsequent neural differentiation after co culture with umbilical cord blood mononuclear cells. Cells were obtained from four human umbilical cords. The mononuclear cells were cultured for 7 d and subsequently co-cultured with mouse fibroblast NIH-3T3 cells for 6 d. The pluripotency of the cells was evaluated by RT-PCR using primers specific for pluripotency marker genes. The pluripotency was also confirmed by adipogenic and osteogenic differentiation. Neural differentiation of the reprogrammed cells was evaluated by immunofluorescence. All co-cultured cells showed adipogenic and osteogenic differentiation capacity. After co-cultivation, cells expressed the pluripotency gene KLF4. Statistically significant differences in cell area, diameter, optical density, and fractal dimension were observed by confocal microscopy in the neurally differentiated cells. Contact in the form of co cultivation of fibroblasts with umbilical cord blood mononuclear fraction for 6 d promoted the reprogramming of these cells, allowing the later induction of neural differentiation. PMID- 25134819 TI - Healthy HIV-1-infected individuals on highly active antiretroviral therapy harbor HIV-1 in their alveolar macrophages. AB - In a prospective cross-sectional study we quantified HIV viral load within the alveolar macrophage in a cohort of healthy HIV-infected subjects who did not have medical comorbidities or smoke cigarettes to determine if alveolar macrophage proviral DNA was associated with alveolar macrophage phagocytic immune dysfunction. We enrolled 23 subjects who underwent bronchoscopy and bronchoalveolar lavage. Alveolar macrophages were isolated and HIV-1 RNA was quantified in the cells using the Abbott RealTime HIV-1 Assay. Proviral DNA was qualitatively measured using a modified version of the HIV-1 RNA assay. Phagocytosis measured by incubating alveolar macrophages with FITC-labeled Staphylococcus aureus and determining fluorescence with a Zeiss inverted microscope. Phagocytic index was calculated as (% positive cells * mean channel fluorescence)/100. Sixteen subjects had (+) proviral DNA and seven had (-) proviral DNA in their alveolar macrophages. Of all subjects 100% in both groups were on highly active antiretroviral therapy (HAART). The median plasma viral load was 0 in both groups. HIV-1-infected subjects with (+) proviral DNA in their alveolar macrophages had a significantly lower median alveolar macrophage phagocytic index compared to those with (-) proviral DNA in their alveolar macrophages [11.8 (IQR 4.8-39.0) vs. 64.9 (IQR 14.0-166.0), p = 0.05]. Alveolar macrophages harbor HIV even in otherwise healthy subjects with undetectable plasma viral loads, representing a potential reservoir for the virus. In addition, HIV viral replication within the macrophage may impair phagocytosis and other immune functions in the lung, leading to an increased risk for lung infection. PMID- 25134820 TI - Treatment of camptocormia with continuous subcutaneous infusions of apomorphine: 1-year prospective pilot study. AB - Camptocormia is defined as a marked dystonic flexion of the trunk in the sagittal plane. Camptocormia responds poorly to botulinum toxin injections, manipulation with dopaminergic treatment, and deep brain stimulation. We designed a prospective pilot study to assess the effect of apomorphine infusions on camptocormia. Five patients were enrolled. All five patients responded well to this treatment. The fact that camptocormia responds so well to apomorphine may be explained by the sustained stimulation of the ventrolateral striatal D1 receptors, alleviating this type of dystonia. PMID- 25134821 TI - Methylome analysis identifies a Wilms tumor epigenetic biomarker detectable in blood. AB - BACKGROUND: Wilms tumor is the most common pediatric renal malignancy and there is a clinical need for a molecular biomarker to assess treatment response and predict relapse. The known mutated genes in this tumor type show low mutation frequencies, whereas aberrant methylation at 11p15 is by far the most common aberration. We therefore analyzed the epigenome, rather than the genome, to identify ubiquitous tumor-specific biomarkers. RESULTS: Methylome analysis of matched normal kidney and Wilms tumor identifies 309 preliminary methylation variable positions which we translate into three differentially methylated regions (DMR) for use as tumor-specific biomarkers. Using two novel algorithms we show that these three DMRs are not confounded by cell type composition. We further show that these DMRs are not methylated in embryonic blastema but are intermediately methylated in Wilms tumor precursor lesions. We validate the biomarker DMRs using two independent sample sets of normal kidney and Wilms tumor and seven Wilms tumor histological subtypes, achieving 100% and 98% correct classification, respectively. As proof-of-principle for clinical utility, we successfully use biomarker DMR-2 in a pilot analysis of cell-free circulating DNA to monitor tumor response during treatment in ten patients. CONCLUSIONS: These findings define the most common methylated regions in Wilms tumor known to date which are not associated with their embryonic origin or precursor stage. We show that this tumor-specific methylated DNA is released into the blood circulation where it can be detected non-invasively showing potential for clinical utility. PMID- 25134822 TI - A comparison of linkage to HIV care after provider-initiated HIV testing and counselling (PITC) versus voluntary HIV counselling and testing (VCT) for patients with sexually transmitted infections in Cape Town, South Africa. AB - BACKGROUND: We examined linkage to care for patients with sexually transmitted infection who were diagnosed HIV-positive via the provider-initiated HIV testing and counselling (PITC) approach, as compared to the voluntary counselling and testing (VCT) approach, as little is known about the impact of expanded testing strategies on linkage to care. METHODS: In a controlled trial on PITC (Cape Town, 2007), we compared HIV follow-up care for a nested cohort of 930 HIV-positive patients. We cross-referenced HIV testing and laboratory records to determine access to CD4 and viral load testing as primary outcomes. Secondary outcomes were HIV immune status and time taken to be linked to HIV care. Logistic regression was performed to analyse the difference between arms. RESULTS: There was no difference in the main outcomes of patients with a record of CD4 testing (69.9% in the intervention, 65.2% in control sites, OR 0.82 (CI: 0.44-1.51; p = 0.526) and viral load testing (14.9% intervention versus 10.9% control arm; OR 0.69 (CI: 0.42-1.12; p = 0.131). In the intervention arm, ART-eligible patients (based on low CD4 test result), accessed viral load testing approximately 2.5 months sooner than those in the control arm (214 days vs. 288 days, HR: 0.417, 95% CI: 0.221 0.784; p = 0.007). CONCLUSION: The PITC intervention did not improve linkage to CD4 testing, but shortened the time to viral load testing for ART-eligible patients. Major gaps found in follow-up care across both arms, indicate the need for more effective linkage-to-HIV care strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN93692532. PMID- 25134823 TI - Exploring repeat HIV testing among men who have sex with men in Cape Town and Port Elizabeth, South Africa. AB - Despite the high prevalence of HIV among men who have sex with men (MSM) - and the general adult population - in South Africa, there is little data regarding the extent to which MSM seek repeat testing for HIV. This study explores reported histories of HIV testing, and the rationales for test seeking, among a purposive sample of 34 MSM in two urban areas of South Africa. MSM participated in activity based in-depth interviews that included a timeline element to facilitate discussion. Repeat HIV testing was limited among participants, with three quarters having two or fewer lifetime HIV tests, and over one-third of the sample having one or fewer lifetime tests. For most repeat testers, the time gap between their HIV tests was greater than the one-year interval recommended by national guidelines. Analysis of the reasons for seeking HIV testing revealed several types of rationale. The reasons for a first HIV test were frequently one-time occurrences, such as a requirement prior to circumcision, or motivations likely satisfied by a single HIV test. For MSM who reported repeat testing at more timely intervals, the most common rationale was seeking test results with a sex partner. Results indicate a need to shift HIV test promotion messaging and programming for MSM in South Africa away from a one-off model to one that frames HIV testing as a repeated, routine health maintenance behavior. PMID- 25134824 TI - Galla Chinensis attenuates cigarette smoke-associated lung injury by inhibiting recruitment of inflammatory cells into the lung. AB - Inflammation is a common feature in the pathogenesis of cigarette smoke (CS) associated diseases. In this study, we investigated the effects of Galla Chinensis (GC) extract on pulmonary inflammatory responses in a CS-exposed mouse model. In vitro studies showed that GC extract reduced MCP-1 production in a dose dependent manner. In addition, the recruitment of inflammatory cells into the lung was significantly inhibited in the bronchoalveolar lavage fluid (BALF) of the GC-treated mice after 3 weeks of daily CS exposure. GC treatment down regulated TNF-alpha, IL-6 and MCP-1 mRNA expression levels in lung tissue. Finally, GC-treated mice showed less emphysematous change of alveolar compared to mice only exposed to CS. Our results show that GC extract reduces lung inflammation and emphysematous change by inhibiting the infiltration of inflammatory cells to the lung. These data indicate that GC extract is a therapeutic candidate for CS-induced lung injury. PMID- 25134825 TI - Diastereoselective synthesis of N-(p-tosylsulfonyl)-2-phenylaziridine over a novel magnetically recyclable Cu(II) catalyst accompanied with the N-inversion assessment at DFT. AB - An experimental and theoretical study has been carried out on diastereoselective aziridation of styrene over a magnetically recyclable copper(II) catalyst: Cu(acac)2/NH2-T/SiO2@Fe3O4NPs. The turnover number (TON) of our heterogeneous catalyst appears considerably higher than that reported for the homogeneous Cu(acac)2. Successive applications of solid Cu(acac)2/NH2-T/SiO2@Fe3O4NPs have a slight effect on its catalytic activity. Between anticipated cis and trans diastereomeric products, formation of only one is suggested by NMR. Even though, the trans-invertomer appears thermodynamically more stable at B3LYP/AUG-cc pVTZ//B3LYP/6-31+G+G* level, we propose formation of the kinetically more stable cis-invertomer due to pi-stacking between the tosyl group and the phenyl of styrene. The possibility of cis-trans conversion is ruled out by the high energy barrier of > 76.9 kcal/mol probed in toluene, CCl4, C7H16, DMSO, CH3CN, and H2O. PMID- 25134826 TI - Temperature dependent reversible p-n-p type conduction switching with colossal change in thermopower of semiconducting AgCuS. AB - Semiconductors have been fundamental to various devices that are typically operated with electric field, such as transistors, memories, sensors, and resistive switches. There is growing interest in the development of novel inorganic materials for use in transistors and semiconductor switches, which can be operated with a temperature gradient. Here, we show that a crystalline semiconducting noble metal sulfide, AgCuS, exhibits a sharp temperature dependent reversible p-n-p type conduction switching, along with a colossal change in the thermopower (DeltaS of ~1757 MUV K(-1)) at the superionic phase transition (T of ~364 K). In addition, its thermal conductivity is ultralow in 300-550 K range giving AgCuS the ability to maintain temperature gradients. We have developed fundamental understanding of the phase transition and p-n-p type conduction switching in AgCuS through temperature dependent synchrotron powder X-ray diffraction, heat capacity, Raman spectroscopy, and positron annihilation spectroscopy measurements. Using first-principles calculations, we show that this rare combination of properties originates from an effective decoupling of electrical conduction and phonon transport associated with electronic states of the rigid sulfur sublattice and soft vibrations of the disordered cation sublattices, respectively. Temperature dependent p-n-p type conduction switching makes AgCuS an ideal material for diode or transistor devices that operate reversibly on temperature or voltage changes near room temperature. PMID- 25134827 TI - KeyPathwayMiner 4.0: condition-specific pathway analysis by combining multiple omics studies and networks with Cytoscape. AB - BACKGROUND: Over the last decade network enrichment analysis has become popular in computational systems biology to elucidate aberrant network modules. Traditionally, these approaches focus on combining gene expression data with protein-protein interaction (PPI) networks. Nowadays, the so-called omics technologies allow for inclusion of many more data sets, e.g. protein phosphorylation or epigenetic modifications. This creates a need for analysis methods that can combine these various sources of data to obtain a systems-level view on aberrant biological networks. RESULTS: We present a new release of KeyPathwayMiner (version 4.0) that is not limited to analyses of single omics data sets, e.g. gene expression, but is able to directly combine several different omics data types. Version 4.0 can further integrate existing knowledge by adding a search bias towards sub-networks that contain (avoid) genes provided in a positive (negative) list. Finally the new release now also provides a set of novel visualization features and has been implemented as an app for the standard bioinformatics network analysis tool: Cytoscape. CONCLUSION: With KeyPathwayMiner 4.0, we publish a Cytoscape app for multi-omics based sub-network extraction. It is available in Cytoscape's app store http://apps.cytoscape.org/apps/keypathwayminer or via http://keypathwayminer.mpi inf.mpg.de. PMID- 25134828 TI - Factors associated with genital human papillomavirus infection among adult females in the United States, NHANES 2007-2010. AB - BACKGROUND: Patients with human papillomavirus (HPV) infection are at risk of developing cancer later in their life. Current research estimates the prevalence of genital HPV infection and explores the factors that are associated with the infection. FINDINGS: The National Health and Nutrition Examination Survey 2007 2010 was used in this research study. The study population included females in the United States aged 18-59 years. The weighted prevalence of HPV infection was 41.9%. An estimated 59.4% of non-Hispanic black females had HPV infection. In a multivariate analysis, number of sexual partners, race, age, education level, marital status, income, smoking, and insurance status were associated with HPV infection. HPV infection was 5.77 times more likely for women with >11 sexual partners compared to women with 0-1 partners. Non-Hispanic black females were 1.87 times more likely to have HPV infection compared to non-Hispanic white females. Participants with only a high school degree had a 58% increased prevalence compared to college-educated women. Uninsured women had a 39% increased prevalence compared to those with insurance. CONCLUSION: This study found that 41.9% of U.S. females aged 18-59 years tested positive for genital HPV infection. We determined that individuals with more sexual partners, with a lower education level, with non-Hispanic black race, and with no insurance were the populations at greatest risk. It is necessary to continue monitoring the prevalence of this infection in the general population to provide a basis for effective treatment and prevention in the target populations. PMID- 25134831 TI - Prostate cancer: Optimizing fluorescence guidance in sentinel node biopsy. PMID- 25134829 TI - Autophagy as a modulator and target in prostate cancer. AB - Autophagy, or 'self-eating', is an adaptive process that enables cells to cope with metabolic, toxic, and even infectious stressors. Although the adaptive capability of autophagy is generally considered beneficial, autophagy can also enhance nutrient utilization and improve growth characteristics of cancer cells. Moreover, autophagy can promote greater cellular robustness in the context of therapeutic intervention. In advanced prostate cancer, preclinical data provide evidence that autophagy facilitates both disease progression and therapeutic resistance. Notably, androgen deprivation therapy, taxane-based chemotherapy, targeted kinase inhibition, and nutrient restriction all induce significant cellular distress and, subsequently, autophagy. Understanding the context dependent role of autophagy in cancer development and treatment resistance has the potential to improve current treatment of advanced prostate cancer. Indeed, preclinical studies have shown that the pharmacological inhibition of autophagy (with agents including chloroquine, hydroxychloroquine, metformin, and desmethylclomipramine) can enhance the cell-killing effect of cancer therapeutics, and a number of these agents are currently under investigation in clinical trials. However, many of these autophagy modulators are relatively nonspecific, and cytotoxicity in noncancerous tissues is still a concern. Moving forward, refinement of autophagy modulation is needed. PMID- 25134833 TI - Paediatrics: A 24 h urine collection is essential in nephrolithiasis evaluation. PMID- 25134834 TI - Prostate cancer: PSA update--no change yet. PMID- 25134837 TI - Paediatric urology: Evasive manoeuvres from bacteria in urinary tract infection. PMID- 25134839 TI - External abdominal oblique muscle ultrasonographic thickness changes is not an appropriate surrogate measure of electromyographic activity during isometric trunk contractions. AB - BACKGROUND: The function of specific abdominal muscles can be assessed using both electromyography (EMG) and ultrasound imaging (USI) thickness measures. However, the relationship between these two measurements is not conclusive during sitting isometric trunk efforts. OBJECTIVE: This study was conducted to assess the relationship between USI thickness and EMG amplitude measures of the right external oblique (EO) muscle during isometric efforts in the sitting position. METHOD: Eighteen subjects performed ramp isometric efforts progressing from 0 to 50% of their maximal voluntary contraction (MVC) in three trunk directions on a dynamometer: (1) forward flexion; (2) right lateral flexion; and (3) left axial rotation. USI and surface EMG amplitude measures of the EO muscle were recorded concomitantly and both normalized against rest values and maximal EMG, respectively. RESULTS: EO muscle was significantly more activated (p < 0.001) during forward flexion (42% on average) and axial rotation (35%) than during lateral flexion (24%). Non-significant (r=0.01; P=0.979) to highly significant (r=0.98; P < 0.0001) and negative and positive Pearson correlations were observed between EMG and EO thickness measures for both flexion and rotation directions. CONCLUSION: The negative correlations between EMG and USI measures as well as the great variability of these correlations across individuals suggest that USI is not a valid measures of EO muscle activity. USI thickness measures should be interpreted with great caution in research and clinical settings. PMID- 25134840 TI - Effect of grain orientations of Cu seed layers on the growth of <111>-oriented nanotwinned Cu. AB - We investigate the growth of Cu films on two different Cu seed layers: one with regular <111>-oriented grains and the other with very strong <111>-preferred orientation. It is found that densely-packed nanotwinned Cu (nt-Cu) can be grown by pulsed electroplating on the strong <111>-oriented Cu seed layer without a randomly-oriented transition layer between the nt-Cu and the Cu seed layer. The electroplated nt-Cu grow almost epitaxially on the seed layer and formed <111> oriented columnar structures. However, with the regular <111>-oriented Cu seed, there is a randomly-oriented transition layer between the nt-Cu and the regular <111>-oriented Cu seed. The results indicate that the seed layer plays a crucial role on the regularity of <111>-oriented nanotwinned Cu. PMID- 25134842 TI - Differences between adults and children: genetics and beyond. AB - Clinical observations and epidemiological studies have highlighted some important differences in disease course and phenotypes between pediatric inflammatory bowel disease (IBD) and adult-onset IBD. Also from a therapeutic angle, the approach to young-onset IBD is different with a more rapid introduction of azathioprine and a high threshold for long and systemic steroid use, which may affect bone mineral density and growth. The observed clinical differences have been an area of scientific research and genetic studies have been the focus of attention. Specific candidate gene studies as well as genome-wide association studies have been performed in pediatric IBD. With the exception of very early-onset IBD occurring before the age of 2 years; no overt differences in genetic susceptibility have been identified. In contrast, very early-onset IBD seems in particular to be a genetic disease with defects in the IL10 signaling pathway being the principal example. This review aims to answer some straightforward questions arising in this topic by giving concise information. PMID- 25134843 TI - Sub-regional volumes changes of the corpus callosum in the drug naive patients with late-onset depression. AB - Although sub-regional analysis methods of the corpus callosum (CC) have been developed, there has been no in vivo magnetic resonance imaging (MRI) study on a sub-regional volume analysis of the CC of late-onset depression (LOD). The aim of this study was to investigate the CC volume differences between LOD subjects and healthy elderly controls using a sub-regional analysis technique. Forty subjects with LOD and thirty nine group-matched healthy control subjects underwent 3T MRI scanning, and sub-regional volumes of the CC were measured and compared between the groups. The volumes of total (F=5.8, p=0.001), the anterior (F=5.2, p=0.001) and the posterior CC (F=5.1, p=0.001) were significantly reduced in the LOD group as compared to the control group. We measured cognitive functions in several different domains (language functions, verbal learning, visuospatial functions, delayed recall, memory consolidation, recognition memory, and executive functions) through the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease. The anterior CC volume in the LOD group showed significant positive correlation with the Verbal Fluency scores. The posterior CC volume in the LOD group was positively correlated significantly with the Word List Memory, the Word List Recall and the Constructional Praxis scores. This study is the first to elaborate the sub-regional volume differences of the CC between controls and LOD patients. These structural changes in the CC might be at the core of the underlying neurobiological mechanisms in LOD. PMID- 25134844 TI - Randomised controlled trials: inferring significance of treatment effects based on confidence intervals. PMID- 25134845 TI - Tailoring the topology of an artificial magnetic skyrmion. AB - Despite theoretical predictions, it remains an experimental challenge to realize an artificial magnetic skyrmion whose topology can be well controlled and tailored so that its topological effect can be revealed explicitly in a deformation of the spin textures. Here we report epitaxial magnetic thin films in which an artificial skyrmion is created by embedding a magnetic vortex into an out-of-plane aligned spin environment. By changing the relative orientation between the central vortex core polarity and the surrounding out-of-plane spins, we are able to control and tailor the system between two skyrmion topological states. An in-plane magnetic field is used to annihilate the skyrmion core by converting the central vortex state into a single domain state. Our result shows distinct annihilation behaviour of the skyrmion core for the two different skyrmion states, suggesting a topological effect of the magnetic skyrmions in the core annihilation process. PMID- 25134838 TI - NUMB inhibition of NOTCH signalling as a therapeutic target in prostate cancer. AB - Prostate cancer is among the most prevalent life-threatening cancers diagnosed in the male population today. Various methods have been exploited in an attempt to treat this disease but these treatments, alongside preventative tactics, have been insufficient to control mortality rates and have usually resulted in detrimental adverse events. An opportunity to devise more-specific and potentially more-effective approaches for the eradication of prostate tumours can be found by targeting specific biological pathways. NUMB (protein numb homologue), a key regulator of cell fate, represents an attractive, actionable target in prostate cancer. NUMB participates in the observed deregulation of NOTCH (neurogenic locus notch homologue protein) signalling in prostate tumours, and the NUMB-NOTCH interaction regulates cell fate. NUMB has potential both as a target for control of prostate tumorigenesis and as a biomarker for identification of patients with prostate cancer who are likely to benefit from NOTCH inhibition. PMID- 25134846 TI - Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies. AB - The subclass distribution of thyroglobulin autoantibodies (TgAb) is debated, whereas their epitope pattern is restricted. Radioidine ((131)I) treatment for Graves' disease (GD) induces a rise in TgAb levels, but it is unknown whether it modifies subclass distribution and epitope pattern of TgAb as well. We collected sera from GD patients before (131) I treatment and 3 and 6 months thereafter. We measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked immunosorbent assay (ELISA) in 25 patients. We characterized the TgAb epitope pattern in 30 patients by inhibiting their binding to (125-) (I) Tg by a pool of four TgAb-Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA by each TgAb-Fab. Total TgAb immunoglobulin (Ig)G rose significantly (P = 0.024). TgAb kappa chains did not change (P = 0.052), whereas TgAb lambda chains increased significantly (P = 0.001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after (131)I (P = 0.008 and P = 0.006, respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to Tg by the TgAb-Fab pool were comparable. A slight, non-significant reduction of the inhibition by the immune-dominant TgAb-Fab A was observed 3 and 6 months after (131)I. We conclude that (131)I treatment for GD increases the levels of the complement-activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass distribution of autoantibodies is dynamic in spite of a stable epitope pattern. PMID- 25134847 TI - Effects of Enteromyxum scophthalmi experimental infection on the neuroendocrine system of turbot, Scophthalmus maximus (L.). AB - Enteromyxum scophthalmi is an intestinal myxosporean parasite responsible for serious outbreaks in turbot Scophthalmus maximus (L.) culture, in North-western Spain. The disease affects the digestive tract, provokes severe catarrhal enteritis, emaciation and high rates of mortality. The digestive parasitization triggers a response with the coordinate participation of immune and neuroendocrine systems through the action of peptides released by enteroendocrine cells and present in nervous elements, acting as neuro-immune modulators. The present study was designed to assess the response of the turbot neuroendocrine system against E. scophthalmi infection. Immunohistochemical tests were applied to sections of the gastrointestinal tract of uninfected and E. scophthalmi infected turbot to characterize the presence of bombesin (BOM), glucagon (GLUC), somatostatin (SOM), leu-enkephalin (LEU) and met-enkephalin (MET). The occurrence of E. scophthalmi in the turbot gastrointestinal tract increased the number of enteroendocrine cells immunoreactive to SOM, LEU and MET. On the other hand, BOM and GLUC immunoreactive cells were less numerous in the gastrointestinal tract of the parasitized turbot. Scarce immunoreactivity to BOM, GLUC and SOM was observed in nerve fibres and neurons of the myenteric plexus of control and infected fish. The results indicate that E. scophthalmi infection in turbot induced changes in the neuroendocrine system, with the diminution of the anorexigenic peptides BOM and GLUC; the increase of enkephalins, related to pro-inflammatory processes; and the increase of SOM, which may cause inhibitory effects on the immune response, constituting a compensatory mechanism to the exacerbated response observed in E. scophthalmi-infected turbot. PMID- 25134848 TI - Effects of emodin and vitamin E on the growth and crowding stress of Wuchang bream (Megalobrama amblycephala). AB - This study aimed to investigate the effects of dietary emodin, high-dose vitamin E and their combination on the growth of Megalobrama amblycephala and its resistance to acute crowding stress. The fish were randomly divided into four groups: a control group fed with basal diet, and three treatment groups fed with basal diet supplemented with 60 mg/kg emodin (the emodin group), 500 mg/kg vitamin E (the vit E group), and 60 mg/kg emodin together with 500 mg/kg vitamin E (the combination group). After 60 days, the fish were exposed to acute crowding stress for 24 h. The results showed that the weight gain of the vit E group, specific growth rate of the vit E group, total serum protein concentration (TP) of the vit E group, serum lysozyme activity of the emodin group, serum superoxide dismutase (SOD) activity of the emodin group, hepatic heat shock protein 70 (HSP70) levels of the vit E group and the emodin group, and serum alanine aminotransferase (ALT) activity of the combination group significantly increased while the weight gain and specific growth rate of the combination group significantly decreased compared with the control group before stress. After crowding stress, the vit E group had improved serum TP 12 h post-stress, hepatic SOD activity 24 h post-stress, and hepatic HSP70 mRNA levels 12 and 24 h post stress while the emodin group had enhanced serum SOD activity 12 and 24 h post stress and hepatic HSP70 mRNA levels 12 and 24 h post-stress, as compared with the control. However, the serum cortisol content of the three treatment groups 12 and 24 h post-stress, ALT activity in the vit E group and emodin group 24 h post stress, and serum alkaline phosphatase and liver catalase activity in the combination group 24 h post-stress were lower than those in the control group. The cumulative mortality was lower in the emodin, vit E, and combination group after Aeromonas hydrophila infection compared with the control group. Therefore, dietary supplementation with 60 mg/kg emodin or 500 mg/kg vitamin E can improve HSP70 mRNA levels and antioxidant capabilities, resistance to crowding stress, and growth in M. amblycephala. However, the combination of emodin and vit E does not have a synergistic effect in M. amblycephala. PMID- 25134849 TI - Stability and retention of micronutrients in fortified rice prepared using different cooking methods. AB - Fortified rice holds great potential for bringing essential micronutrients to a large part of the world population. However, it is unknown whether differences in cooking methods or in production of rice premix affect the final amount of micronutrient consumed. This paper presents a study that quantified the losses of five different micronutrients (vitamin A, iron, zinc, folic acid, and vitamin B12) in fortified rice that was produced using three different techniques (hot extrusion, cold extrusion, and coating) during cooking and five different cooking methods (absorption method with or without soaking, washing before cooking, cooking in excess water, and frying rice before cooking). Fortified rice premix from six different producers (two for each technique) was mixed with normal rice in a 1:100 ratio. Each sample was prepared in triplicate, using the five different cooking methods, and retention of iron, zinc, vitamin A, vitamin B12, and folic acid was determined. It was found that the overall retention of iron, zinc, vitamin B12, and folic acid was between 75% and 100% and was unaffected by cooking method, while the retention of vitamin A was significantly affected by cooking method, with retention ranging from 0% (excess water) to 80% (soaking), depending on the cooking method and producer of the rice premix. No systematic differences between the different production methods were observed. We conclude that different cooking methods of rice as used in different regions of the world do not lead to a major loss of most micronutrients, with the exception of vitamin A. The factors involved in protecting vitamin A against losses during cooking need to be identified. All production techniques of rice premix yielded similar results, showing that coating is not inferior to extrusion techniques. Standard overages (50%) for vitamin B12 and folic acid are too high. PMID- 25134851 TI - Open versus endovascular repair of abdominal aortic aneurysm: Incidence of cardiovascular events in 632 patients in a department of defense cohort over 6 year follow-up. AB - BACKGROUND: Abdominal aortic aneurysm (AAA) is common with unacceptably high rates of mortality and morbidity with unknown rates of complications after repair in the Department of Defense (DoD). METHODS: All patients treated at a DOD or VA clinic or medical facility with a diagnosis of AAA identified by ICD-9 code search were identified by Patient Administration Systems and Biostatistics Activity (PASBA) using the Standard Inpatient Data Record (SIDR) and Composite Ambulatory Patient Encounter Record (CAPER) from January 2006 till December 2011. The primary outcome was death, myocardial infarction (MI), stroke, and cardiac arrhythmia between subjects who underwent endovascular aortic repair (EVAR) or open aortic repair (OAR). RESULTS: A total of 8314 patients were screened to identify 632 patients who underwent surgical repair of non-ruptured AAA. EVAR was performed in 497 patients (78.6%) and OAR in 135 patients (21.4%). Mortality at 30 days was less common in EVAR patients (1.6% vs. 6.7%, p = 0.004), but was not sustained (16.9% vs. 17.8%, p = 0.797). Mean survival free from mortality was not different between the two groups (EVAR vs. OAR: 6.14 +/- 0.13 years vs. 6.11 +/- 0.22 years, p = 0.378). The composite endpoint of MI, stroke, arrhythmia, or death was not different between groups at 30 days (EVAR vs. OAR: 12.9% vs. 14.1%, p = 0.774) or in long-term follow-up population (EVAR vs. OAR: 40.6% vs. 31.9%, p = 0.073) though there was a trend toward higher event rates in the EVAR. The composite endpoint of MI, stroke, and arrhythmia occurred in 198 patients (31%). CONCLUSION: EVAR was associated with lower 30-day mortality rates; however, this benefit was not sustained in longer-term follow-up. There is no difference in the rates of stroke, myocardial infarction, or cardiac arrhythmia at 30 days or in long-term follow-up. PMID- 25134850 TI - Production of the short peptide surfactant DAMP4 from glucose or sucrose in high cell density cultures of Escherichia coli BL21(DE3). AB - BACKGROUND: Peptides are increasingly used in industry as highly functional materials. Bacterial production of recombinant peptides has the potential to provide large amounts of renewable and low cost peptides, however, achieving high product titers from Chemically Defined Media (CDM) supplemented with simple sugars remains challenging. RESULTS: In this work, the short peptide surfactant, DAMP4, was used as a model peptide to investigate production in Escherichia coli BL21(DE3), a classical strain used for protein production. Under the same fermentation conditions, switching production of DAMP4 from rich complex media to CDM resulted in a reduction in yield that could be attributed to the reduction in final cell density more so than a significant reduction in specific productivity. To maximize product titer, cell density at induction was maximized using a fed batch approach. In fed-batch DAMP4 product titer increased 9-fold compared to batch, while maintaining 60% specific productivity. Under the fed-batch conditions, the final product titer of DAMP4 reached more than 7 g/L which is the highest titer of DAMP4 reported to date. To investigate production from sucrose, sucrose metabolism was engineered into BL21(DE3) using a simple plasmid approach. Using this strain, growth and DAMP4 production characteristics obtained from CDM supplemented with sucrose were similar to those obtained when culturing the parent strain on CDM supplemented with glucose. CONCLUSIONS: Production of a model peptide was increased to several grams per liter using a CDM medium with either glucose or sucrose feedstock. It is hoped that this work will contribute cost reduction for production of designer peptide surfactants to facilitate their commercial application. PMID- 25134853 TI - Use of an ankle-foot orthosis improves aerobic capacity in subacute hemiparetic stroke patients. AB - OBJECTIVE: To investigate aerobic capacity with and without an ankle-foot orthosis (AFO) in subacute hemiparetic stroke patients. DESIGN: Prospective crossover intervention study. SETTING: Rehabilitation clinic in secondary care. PATIENTS: Patients diagnosed with first-ever cerebral stroke involving the cortical or subcortical area resulting in hemiparesis (n = 15, 8 men and 7 women; average age, 62.1 years). METHODS: All subjects participated in 2 continuous, symptom-limited, low-velocity graded treadmill exercise stress tests under 2 different conditions, namely, with and without an AFO. The rest interval between tests was at least 48 hours. The order of exercise stress tests was randomized. MAIN OUTCOME MEASUREMENTS: To assess cardiorespiratory responses, oxygen consumption, heart rate, systolic blood pressure, diastolic blood pressure, rate pressure product, and respiratory exchange ratio were measured continuously throughout the test, and peak values were obtained. The rating of perceived exertion was recorded immediately after each test. The percentage of the age predicted maximal heart rate and total exercise duration were also measured. Gait function was assessed by the Six-Minute Walk Test. RESULTS: Using an AFO significantly increased peak oxygen consumption and Six-Minute Walk Test results. Peak values of each of heart rate, systolic blood pressure, diastolic blood pressure, rate-pressure product, and respiratory exchange ratio, rating of perceived exertion, percentage of age-predicted maximal heart rate, and total exercise duration were similar regardless of AFO use. CONCLUSIONS: Use of an AFO may improve aerobic capacity in subacute hemiparetic stroke patients, and may improve energy efficiency and gait endurance. PMID- 25134854 TI - Successful treatment of athletic pubalgia in a lacrosse player with ultrasound guided needle tenotomy and platelet-rich plasma injection: a case report. AB - Athletic pubalgia is a syndrome of persistent groin pain due to chronic repetitive trauma or stress involving the pelvic joints and many musculotendinous structures that cross the anterior pelvis. As a result, the differential diagnosis can be complex, but insertional tendinopathies are the most common. This case report describes a novel approach to the treatment of distal rectus abdominis tendinopathies with ultrasound-guided needle tenotomy and platelet-rich plasma (PRP) injection. After injection, the patient returned to pain-free play at his previous level of intensity. This suggests that PRP may be a useful treatment for this diagnosis. PMID- 25134852 TI - Improvements in lung function and height among cohorts of 6-year-olds with cystic fibrosis from 1994 to 2012. AB - OBJECTIVE: To characterize spirometry and height changes in cohorts of 6-year-old children with cystic fibrosis (CF). STUDY DESIGN: Global Lung Initiative forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC, and the Centers for Disease Control and Prevention height-for-age (HFA) z-scores were generated for 6-year-old children from the Cystic Fibrosis Foundation Patient Registry each year between 1994 and 2012. Z-score mean differences were analyzed by the t test, and time trends of means were analyzed by least squares regression for all children and for subgroups of sex, F508del mutation genotype, Medicaid insurance, and prenatal/newborn screening identification. Z-score distributions were compared using the 2-sample Kolmogorov-Smirnov test. RESULTS: A total of 11 670 children with CF were studied, of whom 50.5% were males, 50.2% had the F508del/F508del genotype, and 46.6% were insured by Medicaid. Mean HFA, FEV1, and FVC z-scores increased significantly over the period in the entire cohort and in all subgroups (P < .001), but FEV1/FVC z-scores were below normal and did not change significantly. In 2012, children identified by screening had significantly higher mean HFA (P = .002), FEV1 (P < .001), and FVC (P < .001) z scores compared with children not screened, with 90% of FVC and 71.4% of FEV1z scores greater than predicted by the normal distribution. FEV1/FVC z-scores were not different between the children who were and were not screened. CONCLUSION: Consistent, significant increases in HFA, FEV1, and FVC occurred between 1994 and 2012, but FEV1/FVC, a measure of airway obstruction, did not change appreciably during this period. FVC and FEV1z-score distributions suggest that normative equation reference populations underpredict lung volumes of children with CF, but the reasons for this remain unclear. PMID- 25134855 TI - Drug loaded homogeneous electrospun PCL/gelatin hybrid nanofiber structures for anti-infective tissue regeneration membranes. AB - Infection is the major reason for guided tissue regeneration/guided bone regeneration (GTR/GBR) membrane failure in clinical application. In this work, we developed GTR/GBR membranes with localized drug delivery function to prevent infection by electrospinning of poly(epsilon-caprolactone) (PCL) and gelatin blended with metronidazole (MNA). Acetic acid (HAc) was introduced to improve the miscibility of PCL and gelatin to fabricate homogeneous hybrid nanofiber membranes. The effects of the addition of HAc and the MNA content (0, 1, 5, 10, 20, 30, and 40 wt.% of polymer) on the properties of the membranes were investigated. The membranes showed good mechanical properties, appropriate biodegradation rate and barrier function. The controlled and sustained release of MNA from the membranes significantly prevented the colonization of anaerobic bacteria. Cells could adhere to and proliferate on the membranes without cytotoxicity until the MNA content reached 30%. Subcutaneous implantation in rabbits for 8 months demonstrated that MNA-loaded membranes evoked a less severe inflammatory response depending on the dose of MNA than bare membranes. The biodegradation time of the membranes was appropriate for tissue regeneration. These results indicated the potential for using MNA-loaded PCL/gelatin electrospun membranes as anti-infective GTR/GBR membranes to optimize clinical application of GTR/GBR strategies. PMID- 25134856 TI - Feasibility and validity of telephone triage for adverse events during a voluntary medical male circumcision campaign in Swaziland. AB - BACKGROUND: Voluntary medical male circumcision (VMMC) reduces HIV acquisition among heterosexual men by approximately 60%. VMMC is a surgical procedure and some adverse events (AEs) are expected. Swaziland's Ministry of Health established a toll-free hotline to provide general information about VMMC and to manage post-operative clinical AEs through telephone triage. METHODS: We retrospectively analyzed a dataset of telephone calls logged by the VMMC hotline during a VMMC campaign. The objectives were to determine reasons clients called the VMMC hotline and to ascertain the accuracy of telephone-based triage for VMMC AEs. We then analyzed VMMC service delivery data that included date of surgery, AE type and severity, as diagnosed by a VMMC clinician as part of routine post operative follow-up. Both datasets were de-identified and did not contain any personal identifiers. Proportions of AEs were calculated from the call data and from VMMC service delivery data recorded by health facilities. Sensitivity analyses were performed to assess the accuracy of phone-based triage compared to clinically confirmed AEs. RESULTS: A total of 17,059 calls were registered by the triage nurses from April to December 2011. Calls requesting VMMC education and counseling totaled 12,492 (73.2%) and were most common. Triage nurses diagnosed 384 clients with 420 (2.5%) AEs. According to the predefined clinical algorithms, all moderate and severe AEs (153) diagnosed through telephone-triage were referred for clinical management at a health facility. Clinicians at the VMMC sites diagnosed 341 (4.1%) total clients as having a mild (46.0%), moderate (47.8%), or severe (6.2%) AE. Eighty-nine (26%) of the 341 clients who were diagnosed with AEs by clinicians at a VMMC site had initially called the VMMC hotline. The telephone-based triage system had a sensitivity of 69%, a positive predictive value of 83%, and a negative predictive value of 48% for screening moderate or severe AEs of all the AEs. CONCLUSIONS: The use of a telephone-based triage system may be an appropriate first step to identify life-threatening and urgent complications following VMMC surgery. PMID- 25134858 TI - Factors predicting the development of pressure ulcers in an at-risk population who receive standardized preventive care: secondary analyses of a multicentre randomised controlled trial. AB - AIMS: To identify predictive factors associated with the development of pressure ulcers in patients at risk who receive standardized preventive care. BACKGROUND: Numerous studies have examined factors that predict risk for pressure ulcer development. Only a few studies identified risk factors associated with pressure ulcer development in hospitalized patients receiving standardized preventive care. DESIGN: Secondary analyses of data collected in a multicentre randomized controlled trial. METHODS: The sample consisted of 610 consecutive patients at risk for pressure ulcer development (Braden Score <17) receiving standardized preventive care measures. Patient demographic information, data on skin and risk assessment, medical history and diagnosis were collected during 26 months (December 2007-January 2010). Predictive factors were identified using multivariate statistics. RESULTS: Pressure ulcers in category II-IV were significantly associated with non-blanchable erythema, urogenital disorders and higher body temperature. Predictive factors significantly associated with superficial pressure ulcers were admission to an internal medicine ward, incontinence-associated dermatitis, non-blanchable erythema and a lower Braden score. Superficial sacral pressure ulcers were significantly associated with incontinence-associated dermatitis. CONCLUSIONS: Despite the standardized preventive measures they received, hospitalized patients with non-blanchable erythema, urogenital disorders and a higher body temperature were at increased risk for developing pressure ulcers. RELEVANCE TO CLINICAL PRACTICE: Improved identification of at-risk patients can be achieved by taking into account specific predictive factors. Even if preventive measures are in place, continuous assessment and tailoring of interventions is necessary in all patients at risk. Daily skin observation can be used to continuously monitor the effectiveness of the intervention. PMID- 25134857 TI - The relationship between physician case volume and in-hospital mortality of critically ill children with a diagnosis of pneumonia: a cross-sectional observational analytical study. AB - PURPOSE: The aim of this study is to examine the relationship between physician case volume and the outcomes of critically ill children with pneumonia. MATERIALS AND METHODS: This is a population-based cohort study analyzed data provided from by the National Health Insurance Research Database of Taiwan, 2006-2009. Children (aged 3 months to 17 years) having records of intensive care unit (ICU) admission and a diagnosis of pneumonia were included. A total of 9754 critically ill children and 1042 attending physicians were enrolled. The children were assigned to 1 of 4 groups based on the physician's pneumonia case volume. RESULTS: The patients in the very high case volume group had a significantly lower length of hospital stay, in-hospital mortality rate, and hospitalization expenses, and a significantly higher ratio of ICU to hospital stays than the other 3 groups (P<.001). The probability of death tended to be lower when the physician's case volume was higher. The risk-adjusted odds ratio for in-hospital mortality of very high case volume group was 0.48 (95% confidence interval, 0.35-0.65; P<.001) compared to low case volume group. CONCLUSIONS: A higher physician's pneumonia case volume is associated with a lower length of hospital stay, lower in-hospital mortality rate, and lower hospitalization expenses among critically ill children with pneumonia. PMID- 25134859 TI - Use of the donor lung after asphyxiation or drowning: effect on lung transplant recipients. AB - BACKGROUND: With the relative paucity of acceptable donors for lung transplantation, criteria for extended donor consideration are being explored. We sought to evaluate the suitability of donors whose cause of death was asphyxiation or drowning (A/D) as a potential option to enlarge the donor pool. METHODS: We queried the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research registry for lung transplantation from 1987 to 2010 to assess associations between cause of death and recipient survival using the Kaplan-Meier method. To adjust for potential confounders, we used a Cox proportional hazards model and a logistic regression model to evaluate incidence of rejection within the first year. RESULTS: There were 18,250 adult primary lung transplantations performed, with 309 A/D donors. There was no difference in survival between groups (log-rank, p = 0.52). There were no differences in demographics, length of stay, airway dehiscence, lung allocation score (LAS), or ischemic time in univariate analysis (all p > 0.05). The A/D lung recipients had fewer deaths from pulmonary causes (5.8% versus 9.5%; p = 0.02). Proportional hazards analysis was significant for double lung transplantation (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.8-0.9), height difference (HR, 1.002; 95% CI, 1.00-1.003), donor age greater than 50 years (HR, 0.89; 95% CI, 0.83 0.96), and recipient age greater than 55 years (HR, 0.8; 95% CI, 0.76-0.84). A/D cause of death did not impact survival in multivariate analysis. CONCLUSIONS: A/D as a donor cause of death was not associated with poor long-term survival or incidence of rejection in the first year after transplantation. Donor cause of death by A/D, when carefully evaluated and selected, should not automatically exclude the organ from transplant consideration. These results provide important justification for potentially broadening the donor pool safely. PMID- 25134860 TI - Impact of perioperative glycemic control strategy on patient survival after coronary bypass surgery. AB - BACKGROUND: Glycemic control in the perioperative period decreases mortality and morbidity, but data are scarce with regard to the effects of glucose control approaches on survival. We assessed long-term survival in patients treated with 2 strategies of glucose control after first-time isolated coronary artery bypass graft. METHODS: In a previously published trial, patients were prospectively randomized to strict (90-120 mg/dL) or liberal (121-180 mg/dL) glucose control protocols. The aim of this study was to assess long-term data on survival and health-related quality of life based on the original prospective randomized study population. RESULTS: No differences were found in cumulative survival between the strict (95.5%) and liberal (93.5%) target range groups (log-rank = 0.32, p = 0.57) over a mean follow-up of 40.0 +/- 4.4 months. Physical health-related quality of life significantly improved in all patients from baseline to 6 months after surgery (F = 17.73, p < 0.001), and there were no differences in improvement of health-related quality of life between the 2 target range groups (F = 0.15, p = 0.70). CONCLUSIONS: These results support our previous findings and indicate that a liberal glycemic control strategy after coronary artery bypass leads to survival rates and improvements in health-related quality of life that are similar to those achieved with a strict target range. In addition, the liberal strategy is superior in glucose control and target range management. PMID- 25134861 TI - Contemporary surgical approaches and outcomes in adults with Kommerell diverticulum. AB - BACKGROUND: Surgery in patients with Kommerell diverticulum (KD) is controversial. Although the presence of symptoms is an accepted indication, the KD itself may be a risk factor for dissection and rupture, although size criteria for operation are undefined. METHODS: A retrospective review of 19 adult patients who underwent surgical treatment of KD between March 2004 and June 2013 was performed. Mean age was 48 years (range, 32 to 68 years). Fifteen patients were female, 15 were symptomatic, and 13 had a right aortic arch. Sixteen patients with aberrant subclavian artery underwent a two-stage procedure involving subclavian-common carotid artery transposition or bypass followed by aortic resection, including origin of the KD, with interposition graft reconstruction. Aortic resection was performed with left heart bypass (n = 10) or deep hypothermic circulatory arrest (n = 9). RESULTS: There were no deaths or strokes. Complications after aberrant subclavian artery revascularization were transient ptosis (n = 3), graft occlusion (n = 1), recurrent laryngeal nerve injury (n = 1),phrenic nerve injury (n = 1), and reintubation (n = 1). Complications after aortic resection were intraoperative type A dissection (n = 1), phrenic nerve injury (n = 1), chylothorax (n = 1), and transient neurologic dysfunction (n = 1). Mean hospital stay after aberrant subclavian artery revascularization was 2 +/- 2 days and after aortic resection, 6.4 +/- 2.4 days. Of 18 available pathology specimens, all 18 showed medial degeneration. Mean follow-up was 3.3 years. CONCLUSIONS: This is the largest reported single-center experience with the surgical management of KD in adults, verifying its safety and efficacy. The high percentage of KD with medial degeneration suggests asymptomatic patients with an enlarged KD also may benefit from resection. PMID- 25134862 TI - Surgical treatment of metachronous second primary lung cancer. AB - BACKGROUND: Many studies have demonstrated that patients with metachronous second primary lung cancer (MSPLC) benefit from surgery. Owing to the lack of uniform criteria and prospective randomized trials, the extent of resection remains controversial, and prognostic factors are still not fully clear. The present study aimed to assess surgical treatment of MSPLC and identify prognostic factors of outcome. METHODS: This retrospective analysis included 143 patients who underwent surgical resection of MSPLC in our department from January 2006 to December 2011. Predictors of postoperative complications were analyzed with the binary logistic regression method. Survival was analyzed with Kaplan-Meier and Cox regression methods. RESULTS: Operative mortality was 1.4%, and the complication rate was 34.3%. Age more than 70 years was an independent risk factor for postoperative complications. The overall 5-year survival after resection of MSPLC was 54.5%. TNM stage II or higher (p = 0.025), 20 or more pack years of smoking (p = 0.037), and tumor size greater than 2 cm (p = 0.033) were independent negative prognostic factors for survival. For stage I disease, completion pneumonectomy had a lower 5-year survival rate than others, 44.8% and 65.9, respectively (p = 0.039); lobectomy and sublobar resection have a 5-year survival of 77.1% and 56.7%, respectively (p = 0.203). CONCLUSIONS: Surgical treatment of MSPLC is safe and effective. TNM stage I, tumor size 2 cm or less, or less than 20 pack-years smoking are predictors of improved survival. Sublobar resection is acceptable. For stage I disease, lobectomy tends to be associated with better survival than sublobar resection, although the difference is not significant, and completion pneumonectomy is not recommended. Long-term follow-up is necessary even after curative resection of lung cancer. PMID- 25134863 TI - Predictors of early recurrence for node-negative t1 to t2b non-small cell lung cancer. AB - BACKGROUND: Recurrence develops in nearly one-third of patients who undergo complete resection for non-small cell lung cancer (NSCLC). We sought to identify predictors of early recurrence (<2 years) in node-negative T1 to T2b NSCLC. METHODS: We used a 10-year (1999 to 2008) single-institution retrospective review of a prospectively maintained lung cancer database. Exclusion criteria included carcinoid, adenocarcinoma in situ, and minimally invasive adenocarcinoma histologies, and any induction therapy. Patient demographics, clinical, and pathologic variables were analyzed. Recurrence was confirmed histologically in 86 patients (85%) or radiographically in 16 (15%). Univariable and multivariable logistic regression (C statistic = 0.7) and Cox proportional hazards analyses were performed (p < 0.05 is significant). RESULTS: An R0 resection of a node negative T1 to T2b NSCLC was performed in 532 patients. Procedures included lobectomy in 436, segmentectomy in 47, and wedge resection in 49. Recurrence was present in 102 patients (19%) and was locoregional in 33 (32%), distant in 40 (39%), and multisite in 29 (29%). T size, tumor histology, tumor grade, smoking status, maximum standardized uptake value, and albumin were not associated with recurrence. Multivariable predictors of recurrence were lymphovascular invasion (odds ratio, 2.48), sublobar resection (odds ratio, 2.37), and age (odds ratio, 0.96). Recurrence was independently associated with lung cancer-specific death (relative risk, 11.78; 95% confidence interval, 5.46 to 25.36; p < 0.001) and overall mortality (relative risk, 1.27; 95% confidence interval, 1.16 to 1.39, p < 0.001). CONCLUSIONS: We demonstrate a 19% early recurrence rate in R0 resected node-negative T1 to T2b NSCLC. The identification of unique predictors of recurrence is an important step toward defining a patient population that may benefit from adjuvant therapy. PMID- 25134864 TI - Significance of low peak Doppler velocity in the proximal sano conduit in hypoplastic left heart syndrome. AB - BACKGROUND: The Sano modification of the Norwood operation is a well-established first step palliation for hypoplastic left heart syndrome (HLHS). Theoretically, the first point of resistance to pulmonary flow should be in the proximal Sano, generating high Doppler flow velocity. Paradoxically, however, some patients have low gradients in the proximal Sano conduit. The objective of this study was to determine the hemodynamic and anatomic significance of low proximal Sano Doppler flow velocity and its clinical implications. METHODS: Doppler-derived peak gradients in the proximal Sano conduits were measured in HLHS patients after Norwood-Sano surgery over a 4-year period and confirmed by cardiac catheterization within 2 to 4 weeks. Clinical outcomes of patients with proximal Sano gradients of 30 mm Hg or less (group 1) were compared with patients whose gradient was greater than 30 mm Hg (group 2). RESULTS: Of the 53 patients, 21 (40%) belonged to group 1. Patients in group 1 had smaller ostial right and left pulmonary artery (PA) diameter (3.2 +/- 1.2 mm versus 4.5 +/- 1.8 mm, p = 0.03; and 3.4 +/- 1.2 mm versus 5.6 +/- 2.1 mm, p = 0.01) when compared with patients in group 2. Patients (7 of 10) who needed either balloon angioplasty of a distal Sano or proximal branch PA were from group 1 (p = 0.01). Patients in group 1 had higher rates of unintended PA interventions (33% versus 9%) and complications (48% versus 16%) compared with group 2. CONCLUSIONS: Low peak Doppler flow velocity in the proximal Sano correlates with the presence of either distal Sano stenosis or proximal branch PA stenosis. These patients require close follow-up in the interstage period and may need earlier intervention. PMID- 25134865 TI - Cost effectiveness of teratology counseling - the Motherisk experience. AB - BACKGROUND: While the benefits of evidence-based counseling to large numbers of women and physicians are intuitively evident, there is an urgent need to document that teratology counseling, in addition to improving the quality of life of women and families, also leads to cost saving. The objective of the present study was to calculate the cost effectiveness of the Motherisk Program, a large teratology information and counseling service at The Hospital for Sick Children and the University of Toronto. METHODS: We analyzed data from the Motherisk Program on its 2012 activities in two domains: 1) Calculation of cost-saving in preventing unjustified pregnancy terminations; and 2) prevention of major birth defects. Cost of pregnancy termination and lifelong cost of specific birth defects were identified from primary literature and prorated for cost of living for the year 2013. RESULTS: Prevention of 255 pregnancy terminations per year led to cost savings of $516,630. The total estimated number of major malformations prevented by Motherisk counseling in 2012 was 8.41 cases at a total estimated cost of $9,032,492. CONCLUSIONS: With an estimated minimum annual prevention of 8 major malformations, and numerous unnecessary terminations of otherwise- wanted pregnancies, a cost saving of $10 million can be calculated. In 2013 the operating budget of Motherisk counseling totaled $640,000. Even based on the narrow range of activities for which we calculated cost, this service is highly cost- effective. Because most teratology counseling services are operating in a very similar method to Motherisk, it is fair to assume that these results, although dependent on the size of the service, are generalizable to other countries. PMID- 25134866 TI - The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease. AB - BACKGROUND: Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD. METHODS: The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae. RESULTS: OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B(H1069Q), but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species. CONCLUSIONS: OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD. GENERAL SIGNIFICANCE: All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment. PMID- 25134867 TI - Psychopharmacology. AB - Primary care providers (PCPs) are frequently responsible for the pharmacologic management of mood disorders, and the PCP is often an important member of the clinical team in the management of bipolar disorder and schizophrenia. Not only is a good understanding of psychopharmacology important for the effective treatment of psychiatric disease, it is also necessary for patient safety. Clinicians should understand the side effects and the medication interactions associated with psychotropic medications. This article reviews mechanisms of action, indications, dosing, side effects, medication interactions, and general management considerations for common medications used to treat psychiatric conditions encountered in the primary care setting. PMID- 25134868 TI - Office-based screening of common psychiatric conditions. AB - Depression and anxiety disorders are common conditions with significant morbidity. Many screening tools of varying length have been well validated for these conditions in the office-based setting. Novel instruments, including Internet-based and computerized adaptive testing, may be promising tools in the future. The best evidence for cost-effectiveness currently is for screening of major depression linked with the collaborative care model for treatment. Data are not conclusive regarding comparative cost-effectiveness of screening for multiple conditions at once or for other conditions. This article reviews screening tools for depression and anxiety disorders in the ambulatory setting. PMID- 25134869 TI - Major depression. AB - Major depression is a common, disabling condition seen frequently in primary care practices. Non-psychiatrist ambulatory providers are increasingly responsible for diagnosing, and primarily managing patients suffering from major depressive disorder (MDD). The goal of this review is to help primary care providers to understand the natural history of MDD, identify practical tools for screening, and a thoughtful approach to management. Clinically challenging topics like co morbid conditions, treatment resistant depression and pharmacotherapy selection with consideration to side effects and medication interactions, are also covered. PMID- 25134870 TI - Anxiety disorders in primary care. AB - Anxiety disorders are the most common psychiatric condition presenting to primary care practitioners. Yet they can be easily overlooked or misdiagnosed. Patients that struggle with anxiety disorders are more likely to seek treatment from primary care providers than mental health specialists. Given the costs in terms of debilitation and associated financial burden, and increased risk of suicide, the identification and successful treatment of anxiety is imperative. By means of clinical acumen and the use of screening tools, the provider can develop expertise in recognition and effective treatment of anxiety disorders. PMID- 25134871 TI - Diagnosis and management of bipolar disorder in primary care: a DSM-5 update. AB - This review discusses the diagnosis and detection of bipolar disorder in the primary care population with recent changes introduced by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the pharmacotherapy and psychosocial management of this psychiatric condition. PMID- 25134872 TI - Borderline personality disorder in the primary care setting. AB - Borderline personality disorder is estimated to be present in approximately 6% of outpatient primary care settings. However, the time and energy spent on this population can greatly exceed what primary care doctors are able to spend. This article gives an overview of borderline personality disorder, including the clinical characteristics, epidemiology, and comorbidities, as well as pharmacologic and most important behavioral management. It is our hope that, with improved understanding of the disorder and skills for managing this population, caring for patients with the disorder can be more satisfying and less taxing for both primary care doctors and their patients. PMID- 25134873 TI - Seasonal affective disorder, grief reaction, and adjustment disorder. AB - Seasonal affective disorder is a subtype of other affective disorders. The most studied treatment is light therapy, although second-generation antidepressants are also an option. Grief reactions are normal for patients experiencing loss, and primary care providers (PCPs) should be aware of both the expected course of grief and the more severe symptoms that indicate complex grief. Adjustment disorder is a time-limited abnormal response to a stressor. PCPs can manage patients with adjustment disorder by arranging counseling, screening for suicidality, assessing for substance abuse, and ruling out other psychiatric diagnoses. At present there are no reliable data to suggest medication management. PMID- 25134874 TI - Approach to the patient with multiple somatic symptoms. AB - Primary care providers play a crucial role in the recognition and appropriate treatment of patients with multiple somatic complaints. Both the number of somatic symptoms and the persistence of symptoms are associated with co-occurring depression or anxiety disorders. It can be challenging to simultaneously address possible medical causes for physical symptoms while also considering an associated psychiatric diagnosis. In this article, strategies to improve the care and outcomes among these patients are described, including collaboration, education about the interaction between psychosocial stressors and somatic symptoms, regularly scheduled visits, focus on improving functional status, and evidence-based treatment of depression and anxiety. PMID- 25134875 TI - Addiction disorders. AB - Substance use disorders are common in primary care settings, but detection, assessment, and management are seldom undertaken. Substantial evidence supports alcohol screening and brief intervention for risky drinking, and pharmacotherapy is effective for alcohol use disorders. Substance use disorders can complicate the management of chronic noncancer pain, making routine monitoring and assessment for substance use disorders an important aspect of long-term opioid prescribing. Patients with opioid use disorders can be effectively treated with methadone in opioid treatment programs or with buprenorphine in the primary care setting. PMID- 25134876 TI - Psychiatric disorders and sleep issues. AB - Sleep issues are common in people with psychiatric disorders, and the interaction is complex. Sleep disorders, particularly insomnia, can precede and predispose to psychiatric disorders, can be comorbid with and exacerbate psychiatric disorders, and can occur as part of psychiatric disorders. Sleep disorders can mimic psychiatric disorders or result from medication given for psychiatric disorders. Impairment of sleep and of mental health may be different manifestations of the same underlying neurobiological processes. For the primary care physician, key tools include recognition of potential sleep effects of psychiatric medications and familiarity with treatment approaches for insomnia in depression and anxiety. PMID- 25134877 TI - Psychiatric care of the older adult: an overview for primary care. AB - As the population ages, primary care providers will be frequently called on to manage psychiatric disorders suffered by their older patients. This overview of delirium, dementia, depression, and alcohol and substance misuse highlights the common presentations and suggests initial approaches to treatment. The challenges facing caregivers are also discussed. PMID- 25134880 TI - Foreword. Psychiatric diagnosis and management in primary care. PMID- 25134879 TI - Medical conditions with neuropsychiatric manifestations. AB - Medical disease sometimes affects patients through neuropsychiatric manifestations. When neuropsychiatric symptoms are predominant, identifying medical disease early in the illness course is imperative because many of these conditions are reversible with appropriate treatment. A high index of suspicion is required on the part of clinicians, particularly when patients also present with physical signs or unexplained symptoms that might suggest a broader, systemic process. The processes that most commonly cause neuropsychiatric symptoms include infectious, autoimmune, endocrinologic, metabolic, and neoplastic diseases. This article focuses on the most common of these conditions, and conditions for which early diagnosis and treatment are particularly important. PMID- 25134878 TI - Primary care for adults on the autism spectrum. AB - Autism spectrum disorder (ASD) is defined by differences in social communication and restricted, repetitive patterns of behavior, interests, or activities. Skills and challenges can change depending on environmental stimuli, supports, and stressors. Quality of life can be improved by the use of accommodations, assistive technologies, therapies to improve adaptive function or communication, caregiver training, acceptance, access, and inclusion. This article focuses on the identification of ASD in adults, referrals for services, the recognition of associated conditions, strategies and accommodations to facilitate effective primary care services, and ethical issues related to caring for autistic adults. PMID- 25134881 TI - Preface. Psychiatric diagnosis and management in primary care. PMID- 25134882 TI - Understanding decreased fertility in women carriers of the FMR1 premutation: a possible mechanism for Fragile X-Associated Primary Ovarian Insufficiency (FXPOI). AB - Fragile X syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1). The full mutation, defined as >200 cytosine-guanine guanine (CGG) triplet repeats, causes FXS. Individuals with 55-199 CGG repeats, classified as premutation carriers, are affected by two distinct disorders depending on their premutation status. Disorders associated with premutation carriers include: Fragile X-associated Tremor Ataxia Syndrome (FXTAS) and Fragile X-associated Primary Ovarian Insufficiency (FXPOI). The molecular similarities of FXTAS and FXPOI (e.g. overabundance of FMR1 transcript and intranuclear inclusions) suggest that similar molecular mechanisms underlie both FXTAS and FXPOI. The current hypothesis describes the underlying mechanism for FXTAS as an mRNA gain-of-function mutation, however the underlying mechanism for FXPOI remains unresolved. New data suggests that repeat associated non-AUG (RAN) translation could underlie FXPOI. PMID- 25134883 TI - Medical resident choices of electronic drug information resources. AB - OBJECTIVE: To determine medical residents' day-to-day use of drug information resources since their choices of these resources, when faced with common questions, are unknown. METHODS: An online survey including simulated drug information questions was administered to 146 medical residents in the Department of General Internal Medicine during July 2012. Residents were given a wide range of choices in drug information resources to answer these questions and were instructed to select what they would choose in actual practice. A score was assigned to each resource corresponding to a "best," "intermediate," or "not good" choice. RESULTS: Seventy-three respondents completed the survey and results were analyzed for statistical significance. Fifty-seven percent of respondents reported receiving no formal training regarding drug information. Statistical analyses revealed there were no significant differences in performance based on postgraduate year (P = .43) or extent of prior training (P = .45). Individual question responses revealed a generally infrequent selection of "best" choices. Less than 10% of the respondents chose the "best" answer for drug information questions related to drug interactions, herbal supplements, adverse events, and medication identification. CONCLUSION: Further training in drug information resource selection is warranted in the medical residency program to increase the frequency of use of higher quality resources. PMID- 25134884 TI - Drug-induced immune thrombocytopenia. AB - Thrombocytopenia is commonly seen in laboratory findings, especially in critically ill patients. Although the incidence is rare, drug-induced immune thrombocytopenia (DITP) is a serious complication that is often overlooked as a cause of thrombocytopenia. Over the last century, extensive research and data collection have been done in an attempt to better characterize DITP. Heparin induced thrombocytopenia is the most common DITP and has distinct pathogenesis, diagnosis, and treatment options. However, other offending medications are less well known and have triggered many questions and constant search for answers. This review will discuss both drug-induced immune-mediated and nonimmune-mediated thrombocytopenias, with a focus on immune-mediated processes. Thrombocytopenia caused by chemotherapy will not be discussed in this article. PMID- 25134885 TI - Measuring the impact of information skills training: a survey of health libraries in England. AB - BACKGROUND: The lack of robust research measuring the impact of NHS based information skills training prompted the West Midlands Regional Trainers' Forum to conduct a post-training survey. METHODS: This is a multi-centred study which collected data from over 60 separate organisations. Survey questionnaires were completed by learners a few weeks after the training event. RESULTS: Five hundred and thirty-four responses were received. 82% of information skills training recipients indicated that they had implemented learning or changed practice as a result of the training. 70% of recipients indicated there had been an impact on patient care. DISCUSSION: The beneficial results from information skills training manifest in a multitude of ways. The results of this study indicate that the learning from information skills training is being used to reduce problems and address the key issues in modern health care. CONCLUSION: The results clearly demonstrate the value of information skills training and its beneficial impact on patient care, lifelong learning and other key NHS functions. This study shows information skills training as an important activity which supports the information literacy agenda, and has a positive impact across the four key functions of library and knowledge services within the NHS. PMID- 25134888 TI - Prevalence of intestinal parasitic infections among communities living in different habitats and its comparison with one hundred and one studies conducted over the past 42 years (1970 to 2013) in Malaysia. AB - Intestinal parasitic infections are among the most common diseases affecting mankind causing major public health problems to billions of people living in developing countries. The aim of this study is to determine the prevalence of intestinal parasites in various communities residing in different habitats in Malaysia and compare the findings with 101 studies conducted over the past 42 years (1970-2013). A cross-sectional study design was conducted with the aid of a questionnaire to collect relevant information about the study population. Faecal samples were examined using the direct smear and formal ether sedimentation techniques. A total of 342 children were examined amongst whom 24.6% were positive for intestinal parasitic infections. Results showed that 32.3% of rural children, 20.6% of urban squatters and 5.4% of children from flats were positive for one or more parasites. The most common parasite encountered was Trichuris trichiura (20.2%) followed by Ascaris lumbricoides (10.5%) and hookworm (6.7%). No case of hookworm was reported in urban children whereas 12.2% of rural children were positive. The most common protozoan parasite detected was Entamoeba coli (3.2%) followed by Giardia intestinalis (1.8%), Entamoeba histolytica (1.8%) and Blastocystis hominis (1.2%). Nearly one-fifth (18.4%) of the children had single infection followed by double (12.0%) and triple infections (1.2%). Orang Asli (indigenous) children (44.3%) had the highest infection rate followed by Indians (20.2%), Malays (14.0%) and Chinese (11.9%). Twenty-eight studies carried out on plantation communities with regards to intestinal parasitic infections in Malaysia from 1970 to 2013 showed a steady decline in the prevalence rate ranging from 95.0% in the seventies to 37.0 % in 2012. Intestinal parasitic infections were more common in Orang Asli communities with prevalence ranging from over 90% in the seventies and fluctuating below 70% in most studies between 2000 to 2013 except for two studies that showed a prevalence of 98.2% and 100%. The prevalence rate among urban squatters, urban residents and those living in flats showed dramatic decrease in prevalence rate. PMID- 25134889 TI - Coexistence of Philodina roseola (Rotifera: Bdelloidea) with larvae of Aedes aegypti in India. AB - The vector mosquitoes, Aedes aegypti and Aedes albopictus of dengue and Chikungunya fever are closely associated with human habitations and adapted to feed on human blood. They undergo larval and pupal development in natural and artificial freshwater collections in the urban and peri-urban environment. Although reports are available about the feeding behaviour of the thriving mosquito larvae, much information is still required to understand the successful survival of Aedes mosquitoes in small and temporary water collections. This study was undertaken to determine the co-existence and prevalence of Philodina roseola and other Bdelloid rotifers in the container habitats of Ae. aegypti mosquitoes. The investigation was conducted in 43 villages which belong to four districts in South India, affected by the epidemic of either dengue or Chikungunya fever. A total of 2093 houses and 12980 containers were examined for Aedes breeding and those containers with Aedes larvae were chosen for further investigation. The investigation showed that, the P. roseola was found associated in 502 (98.2%) containers, P. roseola along with other Philodina sp. in 126 containers (25%) and P. roseola along with other Philodina sp. and other Bdelloid rotifers found in 93 containers (19%). Since the members of the genus Philodina can survive desiccation, reproduce by parthenogenesis, can be transported by wind easily and more importantly, it can incorporate the genome of other organisms including viruses, understanding the co-existence and relationship of Philodina sp. with Aedes larvae would be helpful in the control of Aedes breeding and the control measures can be designed keeping the association of Bdelloids with Aedes in mind. PMID- 25134886 TI - Key informant interviews with coordinators of special events conducted to increase cancer screening in the United States. AB - Special events such as health fairs, cultural festivals and charity runs are commonly employed in the community to increase cancer screening; however, little is known about their effectiveness. The purpose of this study is to assess the activities, screening outcomes, barriers and recommendations of special events to increase breast, cervical and colorectal cancer screening. In-depth interviews were conducted nationally with 51 coordinators of events in June to September 2012. Health fairs and screening days were the most common events conducted, primarily for breast cancer education. Goals were to increase awareness of cancer screening and reach special populations. Evidence-based Community Guide strategies to increase cancer screening employed were: small media, reducing structural barriers, one-on-one education or group education. For each event that provided screening on-site or through referral, a mean of 35 breast, 28 cervical and 19 colorectal cancer screenings were reported. Coordinators made recommendations for further evaluation of special events, and most plan to conduct another special event. These data are novel and provide baseline documentation of activities and recommendations for a commonly used community based cancer screening intervention that lacks evidence of effectiveness. Additional research to better understand the use of special events for increasing cancer screening is warranted. PMID- 25134887 TI - Bilingual children with primary language impairment: 3 months after treatment. AB - BACKGROUND: Evidence on the treatment effectiveness for bilingual children with primary language impairment (PLI) is needed to advance both theory and clinical practice. Of key interest is whether treatment effects are maintained following the completion of short-term intense treatments. AIMS: To investigate change in select language and cognitive skills in Spanish-English bilingual children with PLI 3 months after children have completed one of three experimental treatment conditions. There are two main study aims. First, to determine if skills in Spanish, English and cognitive processing decline, improve or are maintained after treatment has been completed. Second, to determine if differential rates of change are a function of the type of treatment children received. METHODS & PROCEDURES: Participants were 48 children, aged 5:6-11:3, who spoke Spanish and English and were diagnosed with moderate to severe PLI. Participants received 6 weeks of treatment focused on English only (EO), bilingual skills in Spanish and English (BI) or nonlinguistic cognitive processing (NCP). Treatment effects reported in a previous study were determined by comparing pre- and post-treatment performance on a variety of language and cognitive measures. Here we re administered each measure 3 months after completion of the experimental treatments. Hierarchical linear models were calculated for each measure using pre , post- and follow-up testing scores to estimate change trajectories and compare outcomes between treatment conditions. OUTCOMES & RESULTS: Participants in all three treatment conditions either maintained skills or showed improvement even after treatment was discontinued for 3 months. Main findings included (1) comparable, positive rates of change on all English language outcomes for EO and BI conditions; (2) maintenance of Spanish language skills, and (3) modest improvements in NCP following the discontinuation of treatment. CONCLUSIONS & IMPLICATIONS: This study is the first to examine longer-term treatment effects for bilingual school-age children with PLI. Differences in rates of change between languages and between treatment conditions are discussed in terms of social and cognitive processes that impact children's language systems. The main findings have at least two implications for clinical practice: (1) therapy that emphasizes focused practice in language and cognitive processing skills may promote gains in children's language learning abilities; and (2) bilingual treatment does not detract from outcomes in English, the language of the majority community for study participants. PMID- 25134891 TI - Measuring impact on filarial infection status in a community study: role of coverage of mass drug administration (MDA). AB - Lymphatic filariasis is still endemic in many parts of India. The main strategy to implement mass drug administration with DEC and albendazole was added in 2006 to ensure increased impact on the microfilaria (mf) rate in the community. However, the effective coverage remained low in the community leading to lower than desired impact on the parasite population in human. This paper presents the dynamics of participation in annual repeated rounds of mass drug administration in some villages of Kanpur Nagar district in Uttar Pradesh and its impact over the infection rate. It is revealed that after 6 annual rounds of MDA, mf rate could only be reduced by 17.3% in population subgroups who participated only once in comparison to 88% in those who participated in 6 or all annual rounds. PMID- 25134890 TI - Prevalence and genotyping of Cryptosporidium in stool samples collected from children in Taif City (Saudi Arabia). AB - This study was conducted to estimate the frequency of Cryptosporidium infections in Taif (Saudi Arabia). Stool samples from children under 10 years by modified Ziehl-Neelson staining and two PCR techniques were used for genotyping experiments. The microscopic examination showed that, eleven samples were positive for presence of Cryptosporidium. With 11 of 100 samples, DNA extraction and subsequent genotyping was successful. By means of RAPD technique, the genetic similarity among the collected isolates was 55%. The 18S rRNA gene sequences confirmed that all Cryptosporidium-isolates belonged to Cryptosporidium parvum. In comparison with reference strains from different species of Cryptosporidium species from GenBank, all collected isolates belonged to Cryptosporidium hominis and C. parvum clade. The fact that only human genotypes were detected suggests that cryptosporidiosis must primarily be considered as a non zoonotic disease in Taif region. PMID- 25134892 TI - Epidemiology of blood parasitic infections in the urban rat population in peninsular Malaysia. AB - A total of 719 wild rats were captured from four localities representing the west (Kuala Lumpur), east (Kuantan), north (Georgetown) and south (Malacca) to determine the diversity of blood protozoan from the urban wild rat population in peninsular Malaysia. Five rat species were recovered with Rattus rattus diardii being the most dominant species, followed by Rattus norvegicus, Rattus exulans, Rattus annandalei and Rattus argentiventer. Two blood protozoan species were found infecting the rodent population namely, Plasmodium sp. (42.1%) and Trypanosoma lewisi (25.0%). This study reports the presence of Plasmodium sp. for the first time in the rodent population in Malaysia. Two main intrinsic factors were identified affecting the parasitic infections. Trypanosoma lewisi infections were influenced by host age and sex with infections observed higher in male and juvenile rats meanwhile Plasmodium sp. infections were observed almost similar in both sexes. However, infections were higher in sub-adult rats. PMID- 25134893 TI - Multiple resistance of Culex vishnui Theobald against four major classes of insecticides in an agricultural area in Sekinchan, Selangor, Malaysia. AB - The resistance status of riceland Culex vishnui against four major groups of insecticides (i.e., organochlorines, carbamates, organophosphates and pyrethroids) was investigated. Biochemical assays (ESTalpha, ESTbeta, MFO and GST) were also conducted to detect the resistance levels. Throughout a 12-month study period, multiple insecticide resistance was observed in both larvae and adult Cx vishnui. Culex vishnui larvae exhibited low resistance against malathion, temephos and permethrin with resistance ratio (RR) values < 5. In adult bioassay, Cx. vishnui were highly resistant against all tested adulticides with 24h post-treatment mortality < 70%. Correlations between permethrin and malathion resistance, as well as between deltamethrin and cyfluthrin resistance were found in Cx. vishnui. The results indicated that mixed function oxidases activity of Cx. vishnui was the highest compared to ESTalpha, ESTbeta and GST. Spearman rank-order analysis showed that ESTalpha, ESTbeta and GST were involved in multiple resistances in Cx. vishnui. The findings of this study established a baseline of insecticide susceptibility and revealed the effects of agricultural insecticide pressure on the vectors of Japanese encephalitis in Malaysia. PMID- 25134894 TI - First survey of helminths in adult goats in Hunan Province, China. AB - The objective of the present survey was to reveal the prevalence of helminths in adult goats in Hunan Province, the People's Republic of China. From July 2010 through February 2013, a total of 479 goats slaughtered in local abattoirs and markets were examined for the presence of helminths using a helminthological approach. Eighty-six percent of the examined goats were infected with at least one species of helminths. In total, 15 genera of helminths were found representing 2 phyla, 3 classes, 5 orders, and 11 families. Oesophago-stomum, Ostertagia and Haemonchus were the most prevailing nematode genera, Eurytrema was the predominant trematode genus detected, whereas the infection of adult goats with cestodes was not common, with Cysticercus tenuicollis being the most common genus. The worm burdens showed obvious seasonal variation in that nematodes and cestodes were abundant in summer and winter, and the trematodes peaked in winter, which was consistent with the seasonal precipitation of Hunan Province. The geographical distribution of helminths in goats ascended with altitude. Goats in the mountainous areas were more severely infected with helminths than goats in the hilly areas, whereas infection of goats with helminths was much less in the lake areas. The present investigation highlights the high prevalence of helminths in adult goats in Hunan Province, China, which provides baseline data for assessing the effectiveness of future prevention and controlling measures against helminth infection in adult goats in this province and elsewhere. PMID- 25134895 TI - Bleeding outcome during a dengue outbreak in 2005 in the East-coast region of Peninsular Malaysia: a prospective study. AB - During a dengue outbreak in 2005 in the East-coast region of Peninsular Malaysia, one of the worst hit areas in the country at that time, we undertook a prospective study. We aimed to describe the bleeding outcome and changes in the liver and hematologic profiles that were associated with major bleeding outcome during the outbreak. All suspected cases of dengue admitted into the only referral hospital in the region during the outbreak were screened for WHO 2002 criteria and serology. Liver function, hematologic profile and severity of bleeding outcome were carefully documented. The association between symptoms, liver and hematologic impairments with the type of dengue infection (classical vs. hemorrhagic) and bleeding outcome (major vs. non-major) was tested. Dengue fever was confirmed in 183 cases (12.5/100,000 population) and 144 cases were analysed. 59.7% were dengue hemorrhagic fever, 3.5% were dengue shock syndrome and there were 3 in-hospital deaths. Major bleeding outcome (gastrointestinal bleeding, intracranial bleeding or haemoptysis) was present in 14.6%. Elevated AST, ALT and bilirubin were associated with increasing severity of bleeding outcome (all P < 0.05). Platelet count and albumin level were inversely associated with increasing severity of bleeding outcome (both P < 0.001). With multivariable analysis, dengue hemorrhagic fever was more likely in the presence of abdominal pain (OR 1.1, 95% CI 0.02- 1.6) and elevated AST (OR 1.0, 95% CI 1.0 1.1) but the presence of pleural effusion (OR 5.8, 95% CI: 1.1-29.9) and elevated AST (OR 1.008, 95% CI: 1.005-1.01) predicted a severe bleeding outcome. As a conclusion, the common presence of a severe hemorrhagic form of dengue fever may explain the rising death toll in recent outbreaks and the worst impairment in liver and hematologic profiles was seen in major bleeding outcome. PMID- 25134896 TI - The emergence of Leptospira borgpetersenii serovar Arborea as the dominant infecting serovar following the summer of natural disasters in Queensland, Australia 2011. AB - The following research reports the emergence of Leptospira borgpetersenii serovar Arborea as the dominant infecting serovar following the summer of disasters and the ensuing clean up in Queensland, Australia during 2011. For the 12 month period (1 January to 31 December) L. borgpetersenii serovar Arborea accounted for over 49% of infections. In response to a flooding event public health officials need to issue community wide announcements warning the population about the dangers of leptospirosis and other water borne diseases. Communication with physicians working in the affected community should also be increased to update physicians with information such as clinical presentation of leptospirosis and other waterborne diseases. These recommendations will furnish public health officials with considerations for disease management when dealing with future disaster management programs. PMID- 25134897 TI - Screening of antiviral activities in medicinal plants extracts against dengue virus using dengue NS2B-NS3 protease assay. AB - Dengue virus infects millions of people worldwide and there is no vaccine or anti dengue therapeutic available. Screening large numbers of medicinal plants for anti-dengue activities is an alternative strategy in order to find the potent therapeutic compounds. Therefore, this study was designed to identify anti-dengue activities in nineteen medicinal plant extracts that are used in traditional medicine. Local medicinal plants Vernonia cinerea, Hemigraphis reptans, Hedyotis auricularia, Laurentia longiflora, Tridax procumbers and Senna angustifolia were used in this study. The highest inhibitory activates against dengue NS2B-NS3pro was observed in ethanolic extract of S. angustifolia leaves, methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems. These findings were further verified by in vitro viral inhibition assay. Methanolic extract of V. cinerea leaves, ethanol extract of T. procumbens stems and at less extent ethanolic extract of S. angustifolia leaves were able to maintain the normal morphology of DENV2-infected Vero cells without causing much cytopathic effects (CPE). The percentage of viral inhibition of V. cinerea and T. procumbens extracts were significantly higher than S. angustifolia extract as measured by plaque formation assay and RT-qPCR. In conclusion, The outcome of this study showed that the methanolic extract of V. cinerea leaves and ethanol extract of T. procumbens stems possessed high inhibitory activates against dengue virus that worth more investigation. PMID- 25134898 TI - Larvicidal efficacy screening of Anacardaciae crude extracts on the dengue hemorrhagic vector, Aedes aegypti. AB - Vector-borne diseases are still rife because of the re-emergence of diseases transmitted by mosquitoes. The objective of this paper is to evaluate the larvicidal efficacy of crude leaf extract of Mangifera indica, Gluta renghas, and Melanochyla fasciculiflora against vector of dengue hemorrhagic fever, Aedes aegypti. These plant species are endemic species and widely distributed in Malaysian forests. Leaves of Ma. indica, G. renghas and M. fascculiflora were collected from Teluk Bahang National Park, Penang Malaysia. Fractions of leaves were segregated, air-dried, powdered and extracted using Soxhlet with methanol. The solvent was removed by using rotary evaporator to obtain the crude extract. Using WHO standard larval bioassay test method, third instar larvae of Aedes aegypti were exposed to concentration ranging from 200- 4500 ppm of methanol extract for all plant species. Larval mortality was observed after 24 hours exposure. The highest susceptibility and toxicity was recorded by Mangifera indica with the lowest concentration at 800 ppm followed by M. fasciculiflora and G. renghas. This indicates that crude plant extract is very effective in killing Ae. aegypti mosquitoes. This finding may lead to new low cost alternative, environmentally friendly method for mosquito control programs. To our knowledge, this is the first report on larvicidal bioefficacy from endemic Malaysian plants. PMID- 25134899 TI - Prevalence and genotype of Giardia duodenalis from faecal samples of stray dogs in Hualien city of eastern Taiwan. AB - Giardia duodenalis is a zoonotic protozoan parasite that causes diarrhea through waterborne transmission or fecal-oral infection. The cysts are chlorine-resistant and, therefore, can pollute drinking water and induce a pandemic disease. In this study, we aimed to detect G. duodenalis infection in stray dogs in Hualien, Taiwan. We collected faecal samples from 118 dogs and amplified DNA sequences of the beta-giardin gene by nested polymerase chain reactions (nested PCR). Eleven of the 118 faecal samples tested positive for the parasite. The genotype analysis of the 11 samples indicated that 7 samples belonged to assemblage C and four samples belonged to assemblage D. Our study provided a better understanding of the infection rate and genotypes of G. duodenalis in dogs from Hualien City, and human infection could not be induced by this zoonotic infection pathway in Hualien City. PMID- 25134900 TI - Trypanosoma brucei brucei infected rats: micronucleated polychromatic erythrocytes. AB - The emergence of bone marrow micronucleated polychromatic erythrocytes (MN-PCE) in rats experimentally infected with Trypanosoma brucei brucei was examined in order to understand the bone marrow effects in trypanosomiasis infection. Bone marrow was collected for micronucleus assay while blood samples were collected from infected rat for hematological analysis. The results showed evidence of MN PCE at 12.75 +/- 0.65 micronuclei/ 1000 PCE and 9.60 +/- 2.95 micronuclei/1000 PCE for rats infected for 21 days and 14 days respectively. The hematology examination revealed changes in packed cell volume, haemoglobin and red blood cells with concomitant increase in parasitemia. This study revealed that the generation of MN-PCE was induced by an acute infection of T. b. brucei in rats and this highlights an important phase in the pathogenesis of the disease that may indicate possible damage to genetic information. PMID- 25134901 TI - A pre-enrichment step is essential for detection of Campylobacter sp. in turbid pond water. AB - This work aimed to detect Campylobacter species from naturally contaminated turbid pond water by PCR. A total of 16 water samples were collected from a turbid village pond. Four methods of DNA extraction were applied to centrifuge pellets from eight 100 ml pond water samples prior to attempted detection of Campylobacter by PCR without an enrichment step. These methods were (1) Tris-HCl and sodium dodecyl sulfate followed by phenol:chloroform:isoamylalcohol extraction followed by treatment with DNA clean up kit, (2) proteinase K, (3) Chelex(r) 100, and (4) boiling. The other eight pond water samples (10 ml and 100 ml) were filtered and filters were incubated overnight in Preston enrichment broth. The centrifuge pellets obtained from enrichment cultures were treated by proteinase K for DNA extraction. Primers CF03 and CF04 for the flagellin genes (flaA and flaB) of Campylobacter jejuni and Campylobacter coli were used for amplifying the extracted DNA. The DNA extracted from eight-100 ml pond water samples that were not subject to selective enrichment was never amplified with primers CF03 and CF04, hence Campylobacter was not detected. In contrast, the DNA that was from samples that were subjected to a selective enrichment step in Preston broth prior to PCR assay always gave amplified bands of 340-380 bp, therefore the presence of Campylobacter was confirmed. Detection of campylobacters from naturally contaminated, turbid, environmental water may not be feasible by direct PCR assay because of low numbers and the presence of high concentration of humic matter and other PCR inhibitors. The enrichment of water samples in selective broth, however, facilitated PCR detection of Campylobacter probably by increasing cell number and by diluting PCR inhibitors. PMID- 25134902 TI - Identification of Angiostrongylus cantonensis and other nematodes using the SSU rDNA in Achatina fulica populations of Metro Manila. AB - Angiostrongylus cantonensis is a parasitic nematode that causes eosinophilic meningitis in humans. Accidental infection occurs by consumption of contaminated intermediates, such as the giant African land snail, Achatina fulica. This study surveyed the presence of A. cantonensis juveniles in A. fulica populations from 12 sites in Metropolitan Manila, Philippines using the SSU rDNA. Fourteen distinct sequences from 226 nematodes were obtained; of these, two matched A. cantonensis and Ancylostoma caninum, respectively, with 100% identity. Exact identities of the remaining twelve sequences could not be determined due to low percent similarities. Of the sequenced nematodes, A. cantonensis occurred with the highest frequency (139 out of 226). Most of these (131 out of 139) were collected in just one area in Quezon City. Nematode infection of A. fulica in this area and two others from Makati and another area in Quezon City, respectively, were highest, combining for 95% of the total infection. Ancylostoma caninum, on the other hand, was detected in four different sites. A. caninum is a canine parasite, and this is the first report of the nematode in A. fulica. These results cause public health concerns as both A. cantonensis and A. caninum are zoonotic to humans. PMID- 25134903 TI - The blow fly, Chrysomya megacephala, and the house fly, Musca domestica, as mechanical vectors of pathogenic bacteria in Northeast Thailand. AB - The Oriental latrine fly, Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) and the house fly, Musca domestica L., (Diptera: Muscidae) are synanthropic flies which are adapted to live in close association with human habitations, thereby making them likely mechanical vectors of several pathogens to humans. There were two main aims of this study. The first aim was to determine the prevalence of these two fly species from five types of human habitations including: fresh-food markets, garbage piles, restaurants, school cafeterias and paddy fields, in the Muang Ubon Ratchathani and Warinchamrap districts of Ubon Ratchathani province of Northeast Thailand. Flies collection were conducted monthly from September 2010-October 2011 using a reconstructable funnel trap, containing 1 day-tainted beef offal as bait. A total of 7 750 flies (6 401 C. megacephala and 1 349 M.domestica) were collected. The second aim was to examine the potential of these flies to carry pathogenic bacteria. Bacteria were isolated from 994 individual flies collected using a sweep net (555 C. megacephala and 439 M. domestica). A total of 15 bacterial genera were isolated from the external surfaces, comprising ten genera of gram-negative bacteria and five gram-positive bacteria. The most common bacteria isolated from both species were coagulase negative staphylococci, followed by Streptococcus group D non-enterococci. Human pathogenic enteric bacteria isolated were Salmonella sp., Shigella sp., Escherichia coli O157:H7, Salmonella typhi, Bacillus sp., and Enterococcus sp., of which S. typhi is the first report of isolation from these fly species. Other human pathogens included Staphylococcus aureus and Pseudomonas aeruginosa. Not only were the number of C. megacephala positive for bacteria significantly higher than for M. domestica, but they were also carrying ~11-12 times greater bacterial load than M. domestica. These data suggest that both fly species should be considered potential mechanical vectors of bacterial pathogens associated with human habitations year-round in this region of Northeast Thailand. PMID- 25134904 TI - Seroprevalence of Trypanosoma cruzi in stray and pet dogs in Grenada, West Indies. AB - American trypanosomiasis (Chagas disease) caused by the protozoan parasite Trypanosoma cruzi is endemic to parts of South America and the Caribbean. Infected dogs are important in the epidemiology of the parasite as they can play a role in the transmission of the parasite to humans. A total of 399 dog sera (242 stray and 157 pet dogs) were examined for T. cruzi infection; using a qualitative immunochromatographic dipstick test, based on recombinant antigens specific for American trypanosomiasis (Trypanosoma detect rapid test; InBios international, Inc., Seattle, Washington). Overall seroprevalence for T. cruzi was estimated at 10.5% (95% confidence interval: 7.5% to 13.5%); with stray dogs being significantly more affected (p<0.05, chi2). Results from this study indicate that dogs in Grenada are moderately exposed to T. cruzi compared to other areas in the region. PMID- 25134905 TI - Morphology of puparia of flesh flies in Thailand. AB - Puparia of five flesh fly species were investigated for forensic study. Boettcherisca nathani (Lopes, 1961), Boettcherisca peregrina (Robineau-Desvoidy, 1830), Lioproctia pattoni (Senior-White, 1924), Liopygia ruficornis (Fabricius, 1794) and Parasarcophaga (Liosarcophaga) dux (Thomson, 1869) were examined with a scanning electron microscopy (SEM). Differences between species were found in the number and arrangement of papillae in the anterior spiracle, the shape of intersegmental spines between the prothorax and mesothorax and the pattern of spiracular tufts at the posterior spiracle. The anterior spiracle of B. nathani had two rows, comprising 21-27 papillae; while those of B. peregrina and L. pattoni had one or two irregular rows with 24-26 and 20-28 papillae, respectively. Anterior spiracle of L. ruficornis and P. dux had one row of 10-15 papillae. Intersegmental spines between the prothorax and mesothorax and pattern of spiracular tufts at the posterior spiracle are morphologically different. L. ruficornis and P. dux puparia are similar, but the position of the interslit plate between the inner and middle spiracular slits was found to be an important attribute to separate both species. Morphometric analysis on the length and width of puparia of these species revealed statistically different among them. The key for identifying puparia of forensically important flesh flies has been provided. PMID- 25134906 TI - Seasonal occurrence and habitat of two pennellids (Copepoda, Siphonostomatoida) infecting marine ranched black scraper and Korean rockfish in Korea. AB - The seasonal occurrence and habitat of two parasitic copepods, Peniculus minuticaudae (Shiino, 1956) and Peniculus truncatus (Shiino, 1956) (Siphonostomatoida, Pennellidae) infecting the fins of black scraper Thamnaconus modestus and Korean rockfish Sebastes schlegelii, respectively were investigated. The fishes were collected from Tongyeong marine living resources research and conservation center, southern coast of Korea as five per month for two years from July 2011 to June 2013. In total, 391 copepods of P. minuticaudae were collected in two years, in contrast to P. truncatus. Prevalence was 85%, mean intensity was 3.25, and maximum intensity was 33. Season wise, the infestation was observed as the highest in autumn (September-November) season, and the lowest in winter (December- February). It was infested only on fins of black scrapers. Abundance of P. minuticaudae was found on the pectoral fin (43.5%), followed by anal (22.5%), second dorsal (20.5%) and caudal fins (13.5%). Statistically significant interactions were observed between season, infestation and infected regions (P<0.001). It is also reported for the first time in Korea from the fins of wild threadsail filefish Stephanolepis cirrhifer from Busan, Jeju, Tongyeong and Yeosu fish markets. It can be a new record on its host and localities. A total of 51 P. truncatus were collected with the prevalence of 37.5%, mean intensity of 0.37 and maximum intensity of 6. Season wise, infestation was observed as the highest in summer (June-August), and the lowest in winter. Attachment site was the dorsal fin and not found from any other fins of rockfish. Statistically significant interaction was observed between season and infestation (P<0.05). This is the first report on the ecology of these two pennellids. PMID- 25134908 TI - First record of chewing louse Heterodoxus spiniger (Insecta, Phthiraptera, Boopidae) on stray dogs from northern region of Egypt. AB - Heterodoxus spiniger is a rare chewing louse; infest dogs and occasionally cats with expanding geographical distribution. This preliminary report is aimed to record infestation of stray dogs in Kafr El-Sheikh city, Egypt by H. spiniger. Two dogs out of 10 were naturally infected with H. spiniger. This report is the first to demonstrate H. spiniger infestation on dogs in northern regions of Nile delta of Egypt. PMID- 25134907 TI - Genetic variability of the serine-rich Entamoeba histolytica protein gene in clinical isolates from the United Arab Emirates. AB - The genetic diversity of 20 Entamoeba histolytica isolates from asymptomatic individuals from the UAE was investigated by analyzing polymorphism in the serine rich E. histolytica gene (SREHP) by nested polymerase chain reaction (PCR) amplification followed by restriction fragment length polymorphism (RFLP) on DNA extracted directly from stool samples. The SREHP gene was successfully amplified in 15 out of 20 E. histolytica-positive samples. Four out of the remaining five isolates did not amplify for the SREHP gene. Despite successful amplification of the SREHP gene in the fifth isolate, AluI digestion of the amplified PCR product revealed no bands. As a result, all five samples were excluded from the study. Twelve different profiles were obtained from the 15 successfully amplified isolates. Thus, demonstrating extensive genetic variability and reinforcing the argument that E. histolytica has an extremely polymorphic genetic structure. Despite the sample size limitation, a finding in the study was the occurrence of one profile common to one Indian isolate while another profile common to one Pakistani isolate; indicating the possibility of clonal infection. Furthermore, we found one isolate from a Bangladeshi expatriate identical to 2 asymptomatic Bangladeshi isolates reported in an earlier study. No clear association between the different genotypes and the study population demographics was noted. The results also indicated the possibility of strains clustering by region. PMID- 25134909 TI - A preliminary report on ants (Hymenoptera: Formicidae) recovered from forensic entomological studies conducted in different ecological habitats in Malaysia. AB - This study reported the ant species that were recovered from monkey carcasses in three different ecological habitats in Malaysia. The study was conducted from 9 May - 10 October 2007, 6 May - 6 August 2008 and 26 May - 14 July 2009 in forested area (Gombak, Selangor), coastal area (Tanjong Sepat, Selangor) and highland area (Bukit Cincin, Pahang), respectively. Monkey carcass was used as a model for human decomposition in this study. A total of 4 replicates were used in each of the study sites. Ants were observed to prey on eggs, larvae, pupae and newly emerged flies. This study found that ant species could be found at all stages of decomposition, indicating that ants were not a significant indicator for faunal succession. However, different species of ants were obtained from monkey carcasses placed in different ecological habitats. Cardiocondyla sp. was only found on carcasses placed in the coastal area; while Pheidole longipes, Hypoponera sp. and Pachycondyla sp. were solely found on carcasses placed in the highland area. On the other hand, Pheidologeton diversus and Paratrechina longicornis were found in several ecological habitats. These data suggests that specific ant species can act as geographic indicators for different ecological habitats in forensic entomology cases in Malaysia. PMID- 25134910 TI - Quantification of parasite density in 200 microscopic fields underestimates the parasitemia level in malaria patients. AB - The determination of parasitemia in the diagnosis of malaria is a routine practice because it assists the selection of treatment. The techniques used for estimating parasitemia are based on leukocyte counts or on a fixed volume of blood examined in a microscopic field. This study evaluated the concordance between parasitemia estimated by counting parasites in 200 microscopic fields and by counting parasites per 500 leukocytes using the automated leukocyte count as a reference. This study included 403 patients with acute malaria. The parasitemia levels obtained by each method varied greatly. A large discrepancy was observed between the 2 methods with respect to parasitemia results, with 17.6% and 82.4% of the values being overestimates and underestimates, respectively, compared to quantification by the automated leukocyte counts. Thus, these findings reveal the inaccuracy of this method and should be considered by health professionals involved in clinical management of the disease. PMID- 25134911 TI - Different profile of intestinal protozoa and helminthic infections among patients with diarrhoea according to age attending a rural hospital in southern Ethiopia. AB - The aim of this study was to analyze the association of intestinal parasitic diseases with age and gender in patients with diarrhea attending a rural hospital in southern Ethiopia in the period 2007-2012. A total of 32,191 stool examination was performed in patients who presented with diarrhea. The overall prevalence of intestinal parasites in the present study was 26.5%. Predominant parasites detected were Giardia lamblia (15.0%), Entamoeba histolytica/dispar (5.4%), and Ascaris lumbricoides (5.0%). The median of age of diarrheal patients with Hymenolepis species, Schistosoma mansoni and G. lamblia was significantly lower (5 y., 10.5 y., and 18 y., respectively; p<0.001). The median age of diarrheal patients with Taenia species, S. stercoralis, and E. histolytica/dispar was significantly higher (24 y., 24 y., and 20 y., respectively; p<0.01). In conclusion, Giardia lamblia was the most prevalent intestinal parasite and the profile of intestinal parasitic infections is influenced by age. PMID- 25134912 TI - The impact of HIV-1 on neurogenesis: implications for HAND. AB - HIV-1 infection, in addition to its destructive effects on the immune system, plays a role in the development of neurocognitive deficits. Indeed up to 50% of long-term HIV infected patients suffer from HIV-associated neurocognitive disorders (HAND). These deficits have been well characterized and defined clinically according to a number of cognitive parameters. HAND is often accompanied by atrophy of the brain including inhibition of neurogenesis, especially in the hippocampus. Many mechanisms have been proposed as contributing factors to HAND including induction of oxidative stress in the central nervous system (CNS), chronic microglial-mediated neuroinflammation, amyloid-beta (Abeta) deposition, hyperphosphorylated tau protein, and toxic effects of combination antiretroviral therapy (cART). In these review we focus solely on recent experimental evidence suggesting that disturbance by HIV-1 results in impairment of neurogenesis as one contributing factor to HAND. Impaired neurogenesis has been linked to cognitive deficits and other neurodegenerative disorders. This article will highlight recently identified pathological mechanisms which potentially contribute to the development of impaired neurogenesis by HIV-1 or HIV-1-associated proteins from both animal and human studies. PMID- 25134914 TI - Interstitial lung disease during targeted therapy in metastatic renal cell carcinoma: a case series from three centres. AB - Interstitial lung disease (ILD) is an adverse event which occurs also during targeted treatment of patients with metastatic renal cell carcinoma (mRCC). Experiences on ILD-management in mRCC remain limited. mRCC patients treated with everolimus, temsirolimus, or sunitinib at three centres from January 2006 until December 2009 were analysed, retrospectively. Medical records and imaging studies, as well as clinical course, the incidence, diagnostic measures, treatment, and outcome of ILD were assessed. Twenty-six ILD patients (11 %) were identified out of 237 mRCC patients. Median treatment until ILD-diagnosis was 3.8 (range: 1-21.5) months. The ILD-frequency was 2.7 % (n = 6/226) during sunitinib therapy and 19.8 % (n = 20/101) during m-TOR-inhibitor treatment. Cough was the prevailing symptom (69.2 %, n = 18). Bronchoalveolar lavage reviled often lymphocytic (42.9 %, n = 6/14) or eosinophilic cellularity (28.6 %, n = 4/14). Dose reduction (42.3 %, n = 11), treatment interruption (46.2 %, n = 12) or termination (23.1 %, n = 6), and steroid application (34.6 %, n = 9) were common measures in ILD. Interestingly, eosinophilic ILD required pulsed steroids. Improvement occurred in 73.7 % of symptomatic patients. Continuation of targeted therapies was warranted in 65.4 % of ILD patients. No patient died from ILD. ILD during targeted mRCC treatment is common, and supportive measures should be adapted to the clinical course, and potentially in dependence of BAL findings. Re exposure to targeted therapies appears feasible. PMID- 25134916 TI - Metastatic parenchymal renal squamous cell carcinoma with hypercalcemia. PMID- 25134915 TI - Single-strand conformational polymorphism analysis of a common single nucleotide variation in WRAP53 gene, rs2287499, and evaluating its association in relation to breast cancer risk and prognosis among Iranian-Azeri population. AB - The WRAP53 (WD40-encoding RNA antisense to p53) gene encodes an antisense RNA, essential for p53 stabilization and induction upon DNA damage. Single nucleotide polymorphisms (SNPs) in WRAP53 have been associated with risk of cancer, which strengthens the role of WRAP53 in the pathogenesis of human malignancies. In fact, WRAP53 has been considered as a candidate cancer susceptibility gene. Accordingly, we performed a study to examine the association of a frequent genetic variation in WRAP53, rs2287499 (C/G), with breast cancer risk and prognosis among Iranian-Azeri population. A case-control association study, including 206 cases and 203 controls from Iranian-Azeri population, was conducted. Genomic DNA was extracted from peripheral blood and tumor samples by salting-out method. SNP genotyping was carried out by polymerase chain reaction based single-strand conformational polymorphism (PCR-SSCP) technique. The sequence variation of SSCP banding patterns was determined by sequencing. The collected data were analyzed through statistical package for the social sciences software, using Chi-square (chi (2)) or Fisher's exact tests, with a significance level of 0.05. No significant differences in the allele and genotype frequencies between cases and controls were detected. Similarly, no significant associations between genotypes and clinicopathological data were observed. Concisely, no significant overall associations between rs2287499 and breast cancer risk and prognosis were detected in the studied population. The rs2287499 SNP is not associated with breast cancer predisposition in Iranian-Azeri women; it also cannot be used as a molecular biomarker to predict breast cancer prognosis in Iranian-Azeri population. PMID- 25134913 TI - Novel function of PITH domain-containing 1 as an activator of internal ribosomal entry site to enhance RUNX1 expression and promote megakaryocyte differentiation. AB - INTRODUCTION: Altered gene expression coincides with leukemia development and may affect distinct features of leukemic cells. PITHD1 was significantly downregulated in leukemia and upregulated upon PMA induction in K562 cells undergoing megakaryocyte differentiation. We aimed to study the function of PITHD1 in megakaryocyte differentiation. MATERIALS AND METHODS: K562 cells and fetal liver cells were used for either overexpression or downregulation of PITHD1 by retroviral or lentiviral transduction. FACS was used to detect the expression of CD41 and CD42 to measure megakaryocyte differentiation in these cells. Western blot and quantitative RT-PCR were used to measure gene expression. Dual luciferase assay was used to detect promoter or internal ribosomal entry site (IRES) activity. RESULTS: Ectopic expression of PITHD1 promoted megakaryocyte differentiation and increased RUNX1 expression while PITHD1 knockdown showed an opposite phenotype. Furthermore, PITHD1 efficiently induced endogenous RUNX1 expression and restored megakaryocyte differentiation suppressed by a dominant negative form of RUNX1. PITHD1 regulated RUNX1 expression at least through two distinct mechanisms: increasing transcription activity of proximal promoter and enhancing translation activity of an IRES element in exon 3. Finally, we confirmed the function of PITHD1 in regulating RUNX1 expression and megakaryopoiesis in mouse fetal liver cells. CONCLUSION AND SIGNIFICANCE: PITHD1 was a novel activator of IRES and enhanced RUNX1 expression that subsequently promoted megakaryocyte differentiation. Our findings shed light on understanding the mechanisms underlying megakaryopoiesis or leukemogenesis. PMID- 25134917 TI - Multimodality treatment of osteosarcoma of the jaw: a single institution experience. AB - Osteosarcomas of the jaws are rare mesenchymal tumors frequently diagnosed in the fourth decade of life which account for 6 % of all osteosarcomas. This study evaluated the efficacy on the patients outcome of multimodality treatment consisting of surgery, chemotherapy and radiotherapy. The records of 22 patients affected by jaw osteosarcoma treated with a combination of surgery, poly chemotherapy and adjuvant radiotherapy in selected cases were reviewed. Response rate, progression-free survival and overall survival were evaluated. Neoadjuvant chemotherapy resulted in an overall response rate of 83.3 %, necrosis of grade I or II was obtained, respectively, in 44.4 and 55.6 % of the patients, and surgery was radical in all patients. At a median follow-up of 60 months, the 5-year progression-free survival and overall survival were 73.5 and 77.4 %, respectively. These outcome parameters significantly correlated with age at diagnosis and grade of chemotherapy-induced necrosis. A complex multimodality approach including chemotherapy and radiotherapy, along with radical surgery, can maximize the outcome of patients affected by osteosarcoma of the jaws. PMID- 25134918 TI - Clinical value of circulating tumor cells for the prognosis of postoperative transarterial chemoembolization therapy. AB - The aim of this study was to clarify circulating tumor cells (CTCs) count could reflect the effect of postoperative transarterial chemoembolization therapy. A single-blind, two-parallel group, randomized trial was conducted in Guangdong General Hospital, Guangzhou, China, with patients: (1) with biopsy-confirmed hepatocellular carcinoma (HCC) and (2) undergoing partial resection. Patients in transarterial chemoembolization (TACE) group received TACE 1 month after resection, while control group received no managements. The time points for blood collection to count CTCs were as follows: (1) 1 month after resection (also 1 day before TACE); (2) 1 month after TACE; (3) 2 months after TACE; (4) 3 months after TACE; (5) 6 months after TACE; and (6) 1 year after TACE. A diagnosis of recurrence was based on computed tomography scans, magnetic resonance imaging, or digital subtraction angiography. We compared recurrence rate (RR) and CTC counts between groups. Between July 2010 and July 2012, 171 patients (TACE group: n = 81; control group: n = 90) were recruited. After TACE, mean CTC count in TACE group was 1.32 (CI 2.59-3.34), compared with 3.65 (CI 3.43-3.88) in control group (F = 200.89, P<0.05). CTCs counts were statistically significantly between groups at post-TACE time points. In addition, RR of TACE group was 25.9 % (21/81), while the number was 56.7 % (51/90) in control group. RR was statistically significantly between groups (P = 0.031). CTCs count was an important prognostic parameter for postoperative TACE on HCC recurrence. PMID- 25134919 TI - CISD2 expression is a novel marker correlating with pelvic lymph node metastasis and prognosis in patients with early-stage cervical cancer. AB - The CDGSH iron sulfur domain2 (CISD2) is an evolutionarily conserved gene. It functions to control mammalian life span and regulate human breast cancer cells proliferation. However, the characteristics of CISD2 expression and its clinical/prognostic significance are unclear in human tumor. Our study aimed to investigate the expression pattern and clinicopathological significance of CISD2 in patients with early-stage cervical cancer. The mRNA and protein expression levels of CISD2 were analyzed in eight cervical cancer cell lines and eight paired cervical cancer tumors by real-time PCR and Western blotting, respectively. Immunohistochemistry was performed to examine CISD2 protein expression in paraffin-embedded tissues from 149 early-stage cervical cancer patients. Statistical analyses were used to evaluate the clinicopathological significance of CISD2 expression. CISD2 expression was significantly upregulated in cervical cancer cells at both the mRNA and protein levels. Statistical analysis showed a significant correlation of CISD2 expression with the squamous cell carcinoma antigen (P = 0.000), myometrium invasion (P = 0.003), recurrence (P = 0.012), lymphovascular space involvement (P = 0.019) and especially pelvic lymph node metastasis (PLNM; P = 0.000). Patients with higher CISD2 expression had shorter overall survival duration than patients with lower CISD2 expression. Multivariate analysis suggested that CISD2 expression might be an independent prognostic indicator for the survival of patients with early-stage cervical cancer. Our results for the first time suggested that high CISD2 expression was closely correlated with PLNM and poor prognosis in early-stage cervical cancer patients. CISD2 protein might be a novel biomarker for early-stage cervical cancer progression. PMID- 25134922 TI - Fetal cardiac interventricular septum: volume assessment by 3D/4D ultrasound using spatio-temporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL). AB - OBJECTIVE: To determine reference values for fetal interventricular septum (IVS) volume by 3D/4D ultrasound using spatio-temporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL). METHODS: A prospective cross sectional study was conducted on 200 consecutive normal low-risk pregnant women at a gestational age ranging from 18w0d to 33w6d. The volume data sets of the fetal heart were acquired by applying STIC to a four-chamber plane. IVS volume was calculated offline using VOCAL with rotation of 30 degrees (six planes). To assess the correlation of fetal IVS volume as a function of gestational age (GA), Pearson's correlation coefficient (r) and polynomial regression models with adjustments through the coefficient of determination (R(2)) were calculated. The intra-class coefficient (ICC) was used to evaluate intra- and inter-observer reproducibility. RESULTS: A good correlation between GA and fetal IVS volume (r = 0.827) was observed. The mean fetal IVS volume ranged from 0.13 +/- 0.03 cm(3) (0.08-0.18 cm(3)) at 18wd0 of gestation to 1.33 +/- 0.37 cm(3) (0.41-1.98 cm(3)) at 33w6d. The best correlation between fetal IVS volume and GA was exponential: fetal IVS volume = 0.11e(0.139*GA) (R(2 )= 0.785). A good intra- and inter observer reliability were observed, with ICC = 0.999 and 0.991, respectively. CONCLUSIONS: Reference values for fetal IVS volume using STIC and VOCAL by 3D/4D ultrasound between 18w0d and 33w6d of gestation were determined and showed to be reliable and concordant. PMID- 25134920 TI - Breakeven prices for recording of indicator traits to reduce the environmental impact of milk production. AB - A breeding scheme using genomic selection and an indicator trait for environmental impact (EI) was studied to find the most effective recording strategy in terms of annual monetary genetic gain and breakeven price for the recording of indicator traits. The breakeven price shows the investment space for developing a recording system for an indicator trait. The breeding goal consisted of three traits - milk production, functional trait and environmental impact - with economic values of ?83, ?82 and ?-83, respectively. The first scenario included only breeding goal traits and no indicator traits (NoIT). The other scenarios included all three breeding goal traits and one indicator trait (IT) for EI. The indicator traits were recorded on a large scale (stayability after first lactation and stature), medium scale (live weight and greenhouse gases (GHG) measured in the breath of the cow during milking) or small scale (residual feed intake and total enteric methane measured in a respiration chamber). In the scenario with stayability, the genetic gain in EI was over 11% higher than it was in NoIT. The breakeven price of recording stayability was ?8 per record. Stayability is easy to record in the national milk recording system, and its use as an indicator trait for EI would not generate any additional recording costs. Therefore, stayability would be a good indicator trait to use to mitigate EI. The highest genetic gain in EI (23% higher compared to NoIT) was achieved when the GHG measured in the breath of the cow was used as indicator trait. The breakeven price for this indicator trait was ?29 per record in the reference population. Ideally the recording of a specific indicator trait for EI would take place when: (i) the genetic correlation between the IT and EI is high; and (ii) the number of phenotypic records for the indicator trait is high enough to achieve a moderately high reliability of direct genomic values. PMID- 25134923 TI - Effectiveness of aldosterone antagonists for preventing atrial fibrillation after cardiac surgery in patients with systolic heart failure: a retrospective study. AB - Postoperative atrial fibrillation (POAF) is the most common arrhythmia after cardiac surgery. There exist consistent experimental and clinical data suggesting that aldosterone antagonists (AAs) may exert beneficial effects regarding electrical and structural remodeling in failing myocardium. Recently, eplerenone (EPL) has been found to reduce the incidence of nonsurgical AF when added to guideline-recommended therapy in patients with systolic heart failure. Based on these findings, we primarily aimed to evaluate by retrospective analysis the impact of the two AAs, EPL and spironolactone (SPL), given at standard therapeutic doses in preventing new-onset POAF in patients the majority of which had a preoperative ejection fraction (EF) below 40%. A total of 332 patients (298 men/34 women, mean age 64.3 +/- 9 years) without history of AF were included in this analysis; 132 of these patients received long-term EPL or SPL in addition to beta-blockade/statins therapy and 200 patients received neither EPL nor SPL. All patients underwent on-pump coronary artery bypass graft (80%) and/or valvular surgery (20%). In the nonAA group (EF = 35.8 +/- 6%) 90/200 patients (45%) had POAF, while in the AA group (EF = 36.2 +/- 5%) only 40/132 patients (30.3%) developed POAF (P < 0.01, chi (2) test). Multivariate logistic regression analysis revealed that only AAs and left atrial diameter significantly affected the development of POAF even when adjusted for other clinical variables (P < 0.05). In conclusion, AAs significantly reduced the incidence of POAF when added to standard heart failure therapy in patients undergoing on-pump cardiac surgery. PMID- 25134925 TI - Metals in the caudal scutes of Morelet's crocodile (Crocodylus moreletii) from the southern Gulf of Mexico. AB - Caudal scutes were collected from 92 Morelet's crocodiles (Crocodylus moreletii) between May and August 2012, in three Wildlife Management and Use Units (UMAs, from its name in Spanish) and three wild sites in Campeche, Mexico. The UMAs are intensive, with an ex situ approach to manage crocodiles in captivity. The concentrations of arsenic, mercury, lead, nickel, cadmium and chromium were analyzed in each sample. As and Pb were detected in all samples, Hg in 86 and Ni in 74. The metal concentrations estimated were higher than most of the concentrations reported for skin, tail tip and caudal scutes in other crocodilians around the world. The concentration of As, Pb and Ni was significantly greater in the free-ranging groups than in the captive groups in UMAs (p < 0.05). Negative linear relationship was estimated between the snout vent length and the concentration of Pb (in five groups) and Ni (in three groups). In this region C. moreletii is exposed to metals contamination and more studies are necessary to establish if represents a risk to their populations. PMID- 25134926 TI - Aug-MIA-QSPR modeling of the soil sorption of carboxylic acid herbicides. AB - Soil sorption, described as logK OC (the logarithm of the soil/water partition coefficient normalized to organic carbon), was modeled using the augmented multivariate image analysis applied to quantitative structure-property relationship method for a series of 11 carboxylic acid herbicides. The statistical model was found to be highly predictive and reliable to estimate logK OC of other persistent organic pollutants in the soil, which are analogues of the carboxylic acids used in the QSPR model. The QSPR model derived from images corresponding to the chemical structures of the 11 herbicides is superior to the uniparameter model based on the octanol/water partition coefficient (logP) and, in addition, a pattern recognition model was built using principal component analysis. This model allowed clustering and separating compounds with low/moderate soil sorption from those with moderate/high soil sorption (compounds with the aryloxy function) using the second principal component. PMID- 25134927 TI - Preparation and pharmaceutical evaluation of new tacrolimus-loaded solid self emulsifying drug delivery system. AB - The purpose of this study was to develop a novel tacrolimus-loaded solid self emulsifying drug delivery system (SEDDS) using Labrafac as an oil phase. The ternary phase diagram was plotted with Labrafac, Labrasol and Lauroglycol used as an oil, surfactant and co-surfactant, respectively. The liquid SEDDS formulated with Labrasol, Lauroglycol and Labrafac (70:15:15, volume ratio) furnished the smallest emulsion globule size. The solid SEDDS was obtained by spray-drying the liquid mixture containing the liquid SEDDS with 5 % tacrolimus and silicon dioxide. Furthermore, dissolution of tacrolimus from the solid SEDDS and pharmacokinetics in rats was studied compared to the commercial product. The solid SEDDS produced relatively larger emulsion globule size than that exhibited by the corresponding liquid SEDDS. However, this size variation was not significantly different. The solid SEDDS with approximately 280 nm emulsion droplet size improved the dissolution of the drug compared to drug power and the commercial product. It resulted in significantly higher plasma concentration, AUC and Cmax, and shorter Tmax values than did the commercial product (p < 0.05). The enormously enhanced oral bioavailability of tacrolimus in rats was attributed to relatively faster absorption due to accelerated dissolution of the drug from the solid SEDDS. Therefore, this novel solid SEDDS prepared with Labrafac as an oil phase is an excellent way to achieve better bioavailability of tacrolimus given via the oral route. PMID- 25134924 TI - Managing chemotherapy-related cardiotoxicity in survivors of childhood cancers. AB - In the US, children diagnosed with cancer are living longer, but not without consequences from the same drugs that cured their cancer. In these patients, cardiovascular disease is the leading cause of non-cancer-related morbidity and mortality. Although this review focuses on anthracycline-related cardiomyopathy in childhood cancer survivors, the global lifetime risk of other cardiovascular diseases such as atherosclerosis, arrhythmias and intracardiac conduction abnormalities, hypertension, and stroke also are increased. Besides anthracyclines, newer molecularly targeted agents, such as vascular endothelial growth factor receptor and tyrosine kinase inhibitors, also have been associated with acute hypertension, cardiomyopathy, and increased risk of ischemic cardiac events and arrhythmias, and are summarized here. This review also covers other risk factors for chemotherapy-related cardiotoxicity (including both modifiable and non-modifiable factors), monitoring strategies (including both blood and imaging-based biomarkers) during and following cancer treatment, and discusses the management of cardiotoxicity (including prevention strategies such as cardioprotection by use of dexrazoxane). PMID- 25134930 TI - Letter from the editor. PMID- 25134929 TI - An approach to multiscale modelling with graph grammars. AB - BACKGROUND AND AIMS: Functional-structural plant models (FSPMs) simulate biological processes at different spatial scales. Methods exist for multiscale data representation and modification, but the advantages of using multiple scales in the dynamic aspects of FSPMs remain unclear. Results from multiscale models in various other areas of science that share fundamental modelling issues with FSPMs suggest that potential advantages do exist, and this study therefore aims to introduce an approach to multiscale modelling in FSPMs. METHODS: A three-part graph data structure and grammar is revisited, and presented with a conceptual framework for multiscale modelling. The framework is used for identifying roles, categorizing and describing scale-to-scale interactions, thus allowing alternative approaches to model development as opposed to correlation-based modelling at a single scale. Reverse information flow (from macro- to micro scale) is catered for in the framework. The methods are implemented within the programming language XL. KEY RESULTS: Three example models are implemented using the proposed multiscale graph model and framework. The first illustrates the fundamental usage of the graph data structure and grammar, the second uses probabilistic modelling for organs at the fine scale in order to derive crown growth, and the third combines multiscale plant topology with ozone trends and metabolic network simulations in order to model juvenile beech stands under exposure to a toxic trace gas. CONCLUSIONS: The graph data structure supports data representation and grammar operations at multiple scales. The results demonstrate that multiscale modelling is a viable method in FSPM and an alternative to correlation-based modelling. Advantages and disadvantages of multiscale modelling are illustrated by comparisons with single-scale implementations, leading to motivations for further research in sensitivity analysis and run-time efficiency for these models. PMID- 25134928 TI - A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease. AB - In this report, we designed a highly bright bifunctional curcumin analogue CRANAD 28. In vivo two-photon imaging suggested that CRANAD-28 could penetrate the blood brain barrier (BBB) and label plaques and cerebral amyloid angiopathies (CAAs). We also demonstrated that this imaging probe could inhibit the crosslinking of amyloid beta induced either by copper or by natural conditions. PMID- 25134931 TI - A population-based study of pregnancy and delivery characteristics among women with vulvodynia. AB - INTRODUCTION: To examine pregnancy and delivery characteristics of women with and without vulvodynia. METHODS: The authors analyzed 227 vulvodynia cases that were less than 45 years old at pain onset; controls were age matched 1:1 to cases and had no history of vulvar pain. Pregnancy and delivery events were assessed after age at first vulvar pain onset (the reference age) in cases and a matched age in controls. RESULTS: The authors observed no significant difference between cases and controls in achieving pregnancy after reference age. Also, no difference in pregnancy outcome was observed between cases and controls (P = 0.87). There was an indication that cases were more likely to receive a Cesarean section delivery (P = 0.07). In addition, 37.1% of cases who had vaginal delivery versus 11.3% of controls (P < 0.01) reported pain at 2 months postpartum. Comparing only women with vulvodynia, women who had intermittent pain versus constant pain were more than twice as likely to have a pregnancy (adjusted odds ratio 2.26, 95% CI 1.10 4.60). CONCLUSIONS: Women with vulvodynia may be as likely as other women to carry their pregnancy to birth; however, they may experience higher rates of Cesarean section delivery and could reflect a selection towards those women with vulvodynia who have inconsistent pain. PMID- 25134933 TI - Alleviating symptoms of withdrawal from an opioid. AB - INTRODUCTION: Patients who are discharged following surgery on an oral opioid, and who have taken the drug for 2 or more weeks often experience withdrawal symptoms when they try to discontinue the drug. CASE REPORT: Three weeks after discharge, a 44-year-old female patient decided to reduce her oxycodone (OxyContin((r))) dosage from 20 mg three times a day to 20 mg two times a day. She experienced severe withdrawal symptoms. METHOD: To assist her in withdrawing from the remainder of the drug, a protocol using ondansetron was developed. RESULTS: After 10 days, the patient was opioid and withdrawal-symptom free. CONCLUSION: Use of ondansetron along with tapering of the opioid was safe and effective in preventing further withdrawal symptoms. This case should stimulate research with a larger, more diverse population including those with both short term and chronic opioid dependence. PMID- 25134932 TI - Discovery of Fused Triazolo-thiadiazoles as Inhibitors of TNF-alpha: Pharmacophore Hybridization for Treatment of Neuropathic Pain. AB - INTRODUCTION: Neuropathic pain is a complex, chronic pain state that is usually accompanied by tissue injury. With neuropathic pain, the nerve fibers themselves may be damaged, dysfunctional, or injured. METHODS: A series of pharmacophoric hybrids of substituted aryl semicarbazides incorporated into a fused triazolo thiadiazole nucleus were synthesized and evaluated for neuropathic pain activity. After the assessment of neurotoxicity and peripheral analgesic activity, the compounds were evaluated in two peripheral neuropathic pain models, the chronic constriction injury and partial sciatic nerve ligation, to assess their antiallodynic and antihyperalgesic potential. RESULTS: Selected compounds exhibiting promising efficacies (4b, 6a, and 7e) revealed median effective dose (ED50) values ranging from 7.62-28.71 mg/kg in four behavioral assays of allodynia and hyperalgesia (spontaneous pain, tactile allodynia, cold allodynia, and mechanical hyperalgesia). Studies carried out to assess the underlying mechanism revealed that compounds suppressed the inflammatory component of the neuropathic pain by inhibiting tumor necrosis factor (TNF)-alpha and preventing oxidative and nitrosative stress. CONCLUSION: Using a hybrid design approach, the present study identified novel chemical compounds that could be a potential lead for the treatment of neuropathic pain. PMID- 25134934 TI - Outcomes in pain medicine: a brief review. AB - Pain, and particularly chronic pain, is a difficult outcome to measure due to its subjective and multidimensional nature. The Institute of Medicine estimates that 100 million Americans have chronic pain with a cost exceeding half a trillion dollars per year. There is a pressing need to identify appropriate outcome measures to better select and evaluate treatment modalities for these patients. It is also important that we demonstrate an evidence basis for these decisions given the current practice standard. Appropriate selection and implementation of these outcome measures can help accomplish both goals. The purpose of this review is to explore the difficulties and opportunities unique to pain outcome measures. The scope of the problem and impetus for implementation of appropriate measures is initially discussed, followed by requisite evaluation criteria for any measurement instrument. The authors then review frequently employed tools for measuring pain outcomes ranging from univariable and single domain scales to multidimensional instruments. A discussion of possible behavioral and objective measures is pursued, as well as measures of statistical and treatment efficacy. The article closes with a review of recent and ongoing efforts to validate and standardize pain outcome measures and suggests directions for future clinical and research assessment. PMID- 25134937 TI - Redox-reversible niobium-doped strontium titanate decorated with in situ grown nickel nanocatalyst for high-temperature direct steam electrolysis. AB - Composite cathodes based on Sr0.94Ti0.9Nb0.1O3 (STNO) can be utilized for direct steam electrolysis; however, the insufficient electrocatalytic activity limits electrode performance and current efficiency. In this work, redox-reversible (Sr0.94)0.9(Ti0.9Nb0.1)0.9Ni0.1O3 (STNNO) with A-site deficiency and B-site excess has been designed as a cathode material in an oxide-ion-conducting solid oxide electrolyzer for direct steam electrolysis. The XRD, TEM, SEM, EDS, TGA and XPS results together confirm that the exsolution or dissolution of Ni nanoparticles anchored on the STNO surface is completely reversible in the redox cycles. The electrical properties of STNO and STNNO are investigated and correlated to electrode performances. The current efficiency with an STNNO cathode is enhanced by about 20% compared to the values with a bare STNO cathode in 5% H2O/H2/Ar or 5% H2O/Ar at 800 degrees C. The synergetic effect of catalytically active nickel nanoparticles and the redox-stable STNO skeleton contributes to the improved performance and excellent stability of the cathode for steam electrolysis. PMID- 25134935 TI - Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction. AB - In the present study, we investigated whether mesenchymal stem cells (MSCs) overexpressing integrin-linked kinase (ILK) might regulate ventricular remodeling and cardiac function in a porcine myocardial infarction model. ILK-modified MSCs (ILK-MSCs) (n = 8), MSCs (n = 8) or placebo (n = 8) were injected into peri infarct myocardium 7 days after ligation of the left anterior descending coronary artery. ILK expression was confirmed by immunofluorescence, real-time PCR, Western blot analysis, and flow cytometry. In vitro assays indicated increased proliferation and reduced apoptosis of MSCs due to overexpression of ILK. Echocardiographic, single-photon emission computed tomography and positron emission tomography analyses demonstrated preserved cardiac function and myocardial perfusion. Reduced fibrosis, increased cardiomyocyte proliferation, and enhanced angiogenesis were observed in the ILK-MSC group. Reduced apoptosis, as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis, was also noted. In conclusion, ILK promotes MSC proliferation and suppresses apoptosis. ILK-MSC transplantation improves ventricular remodeling and cardiac function in pigs after MI. It is associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This may represent a new approach to the treatment of post-infarct remodeling and subsequent heart failure. PMID- 25134936 TI - Hierarchical functional data with mixed continuous and binary measurements. AB - Motivated by objective measurements of physical activity, we take a functional data approach to longitudinal data with simultaneous measurement of a continuous and a binary outcomes. The regression structures are specified as smooth curves measured at various time-points with random effects that have a hierarchical correlation structure. The random effect curves for each variable are summarized using a few important principal components, and the association of the two longitudinal variables is modeled through the association of the principal component scores. We use penalized splines to model the mean curves and the principal component curves, and cast the proposed model into a mixed effects model framework for model fitting, prediction and inference. Via a quasilikelihood type approximation for the binary component, we develop an algorithm to fit the model. Data-based transformation of the continuous variable and selection of the number of principal components are incorporated into the algorithm. The method is applied to the motivating physical activity data and is evaluated empirically by a simulation study. Extensions for different types of outcomes are also discussed. PMID- 25134938 TI - Cytogenetic mapping of the Muller F element genes in Drosophila willistoni group. AB - Comparative genomics in Drosophila began in 1940, when Muller stated that the ancestral haploid karyotype of this genus is constituted by five acrocentric chromosomes and one dot chromosome, named A to F elements. In some species of the willistoni group such as Drosophila willistoni and D. insularis, the F element, instead of a dot chromosome, has been incorporated into the E element, forming chromosome III (E + F fusion). The aim of this study was to investigate the scope of the E + F fusion in the willistoni group, evaluating six other species. Fluorescent in situ hybridization was used to locate two genes of the F element previously studied-cubitus interruptus (ci) and eyeless (ey)-in species of the willistoni and bocainensis subgroups. Moreover, polytene chromosome photomaps corresponding to the F element (basal portion of chromosome III) were constructed for each species studied. In D. willistoni, D. paulistorum and D. equinoxialis, the ci gene was located in subSectction 78B and the ey gene in 78C. In D. tropicalis, ci was located in subSection 76B and ey in 76C. In species of the bocainensis subgroup, ci and ey were localized, respectively, at subsections 76B and 76C in D. nebulosa and D. capricorni, and 76A and 76C in D. fumipennis. Despite the differences in the subsection numbers, all species showed the same position for ci and ey. The results confirm the synteny of E + F fusion in willistoni and bocainensis subgroups, and allow estimating the occurrence of this event at 15 Mya, at least. PMID- 25134940 TI - Novel agents in CNS myeloma treatment. AB - Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID's seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease. PMID- 25134939 TI - Bone complications among prostate cancer survivors: long-term follow-up from the prostate cancer outcomes study. AB - BACKGROUND: To assess the relationship between androgen deprivation therapy (ADT) exposure and self-reported bone complications among men in a population-based cohort of prostate cancer survivors followed for 15 years after diagnosis. METHODS: The Prostate Cancer Outcomes Study enrolled 3533 patients diagnosed with prostate cancer between 1994 and 1995. This analysis included participants with non-metastatic disease at the time of diagnosis who completed 15-year follow-up surveys to report development of fracture, and use of bone-related medications. The relationship between ADT duration and bone complications was assessed using multivariable logistic regression models. RESULTS: Among 961 surviving men, 157 (16.3%) received prolonged ADT (>1 year), 120 (12.5%) received short-term ADT (? 1 year) and 684 (71.2%) did not receive ADT. Men receiving prolonged ADT had higher odds of fracture (OR 2.5; 95% confidence interval (CI): 1.1-5.7), bone mineral density testing (OR 5.9; 95% CI: 3.0-12) and bone medication use (OR 4.3; 95% CI: 2.3-8.0) than untreated men. Men receiving short-term ADT reported rates of fracture similar to untreated men. Half of men treated with prolonged ADT reported bone medication use. CONCLUSIONS: In this population-based cohort study with long-term follow-up, prolonged ADT use was associated with substantial risks of fracture, whereas short-term use was not. This information should be considered when weighing the advantages and disadvantages of ADT in men with prostate cancer. PMID- 25134941 TI - The role of the bipolar plasmakinetic TURP over 100 g prostate in the elderly patients. AB - BACKGROUND AND PURPOSE: Bipolar plasma kinetic (BP) transurethral resection of prostate (TURP) has been proved to be a safe and effective treatment for benign prostatic enlargement (BPE). However, the role of bipolar TURP on large prostates over 100 g compared with open suprapubic prostatectomy (SP) in elderly patients (>65 years) has not ever been studied before. PATIENTS AND METHODS: A retrospective analysis of patients' medical records between 2007 and 2012 was performed. A total of 102 patients who underwent SP (n = 44) or BP-TURP [Gyrus Plasma KineticTM (Gyrus ACMI, USA)] (n = 58) for obstructive lower urinary tract symptoms due to BPE were included in this retrospective study. Inclusion criteria were age >=65 years, prostate volume >=100 g, International Prostate Symptom Score (IPSS) >=18, and peak urinary flow rate (PFR) <=15 ml/s. Exclusion criteria were urethral stricture, known history of neurogenic bladder due to neural disorders, previous prostate and/or urethral surgery, bladder stone, bladder cancer, and known prostate cancer. Operation time, hospitalization, and catheter removal times were noted. Patients were re-evaluated at postoperative 3rd and 12th months. Evaluated parameters were IPSS, quality of life (QoL), simplified International Index of Erectile Function-5 (IIEF-5), PFR, post-voiding residual urinary volume (PVR). Statistical significance was set at 0.05 and all tests were two-tailed. RESULTS: Preoperative IPSS, PVR, IIEF-5, QoL, and prostate volume were not statistically significantly different between two groups except for PFR. Mean follow-up for BP-TURP and SP groups were 15.0 +/- 5.8 (R: 11-38), 22.1 +/- 11.2 (R: 11-59) months, respectively (p < 0.001). When compared with SP, mean catheter removal time (p < 0.001) and median hospitalization time (p < 0.001) were significantly shorter in BP-TURP group. However, mean operative time was significantly (p < 0.001) longer than SP group and also median resected material weight was significantly lower in the BP-TURP group (p < 0.001). IPSS, QoL, PFR, PVR, and IIEF-5 scores at postoperative 3rd and 12th month were not significantly different between the two groups (p > 0.05). Thirty-three patients had perioperative complications according to the modified Clavien-Dindo system. Thirteen patients (22.4 %) in BP-TURP group and 20 patients (45.4 %) in SP group had complications. In 12th month follow-up visit, four patients presented with urethral stricture, three patients (5.1 %) were in BP-TURP group, and one patient (2.3 %) in SP group (p = 0.455). All strictures were treated with internal urethrotomy. CONCLUSIONS: BP-TURP is a safe and highly effective treatment modality for BPE in the elderly patients with prostate glands over 100 g. Clinical efficacy and postoperative 12th month's results were similar to SP. Larger studies with longer follow-up are needed in order to confirm our findings. PMID- 25134942 TI - Relationship between prehypertension and incidence of chronic kidney disease in a general population: a prospective analysis in central south China. AB - OBJECTIVE: The objective of the study was to investigate whether prehypertension is associated with progression to chronic kidney disease (CKD) in the general population in central south China. METHODS: A prospective cohort study was carried out in 1,703 white-collar workers without preexisting CKD in Changsha in 2006 at baseline. The cohort population was followed for an average of 54 months by annual examinations. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study equation modified by the Chinese coefficient. CKD was defined as positive albuminuria or an estimated GFR <60 mL/min/1.73 m(2). Blood pressure (BP) categories were defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The association of blood pressure and CKD incidence was examined using a Cox regression model adjusted for relevant factors. RESULTS: During the follow-up of cohort, 194 incidences of CKD were recorded. Compared with normotension group, the hazard ratios (95 % confidential intervals) for CKD were 1.25 (1.02-1.85) in prehypertension group, 1.62 (1.07 2.79) in undiagnosed hypertension group, and 1.98 (1.15-3.96) in diagnosed hypertension group. Kaplan-Meier curves showed there was a significant difference in the cumulative incidence of CKD between the different blood pressure categories (log-rank test, P < 0.001). The independent risk factors of CKD were age, estimated glomerular filtration rate (eGFR), systolic blood pressure, and diastolic blood pressure according to the Cox proportional hazard analysis. It was found that 2.4 % in participants with CKD incidences could be described as excessive incidence attributable to prehypertension. CONCLUSION: Prehypertension is significantly associated with CKD in a Chinese urban population. PMID- 25134943 TI - Does the nephrostomy tract length impact the outcomes of percutaneous nephrolithotomy (PNL)? AB - PURPOSE: Different factors can determine the outcomes of percutaneous nephrolithotomy (PNL). We analyzed the effect of tract length (TL) on outcomes after PNL. METHODS: We performed a retrospective review of patients undergoing PNL between 2006 and 2011. Patients with preoperative computed tomography (CT), one percutaneous access tract and follow-up imaging within 3 months were included. TL was defined as distance between the skin to the calyx of puncture as measured on preoperative CT. Measurements were independently performed by two urologists and the average was used for analysis. Stone-free rate (SFR) was defined as zero fragments on follow-up imaging. Factors independently associated with the likelihood of being stone-free after PNL were determined using multivariable analysis adjusted for TL, location of access, the presence of incomplete or complete staghorn calculi and type of follow-up imaging. Complications (Clavien score) were independently assessed. RESULTS: A total of 222 patients were included. Median stone burden and body mass index (BMI) was 239.4 mm(2) and 30.5 [interquartile range (IQR): 25.7-36.2]. The median TL was 85.0 mm (IQR: 70.3-100.0) and highly correlated with BMI (rho = 0.66, p < 0.001). A total of 101 patients (45.5 %) were stone-free. TL was not associated with SFR (p = 0.53). Clavien 1 and 2 complications occurred in 38 (17 %) while Clavien 3 and 4 complications occurred in 17 (8 %) patients. Multivariable analysis revealed no association between complications and TL even when adjusted for gender. CONCLUSIONS: Percutaneous TL is not associated with outcomes of PNL. PNL is a safe and effective treatment for stones in patients with differing body habitus. PMID- 25134944 TI - Open reconstruction of recurrent vesicourethral anastomotic stricture after radical prostatectomy. AB - OBJECTIVES: To determine the outcomes of open vesicourethral anastomotic reconstruction (VUAR) for outlet stenosis following radical prostatectomy (RP). METHODS: Review of all cases of VUAR within an IRB-approved database was performed. Preoperative factors assessed included cancer treatment modality, duration of symptoms, prior treatments, and length of defect. Outcomes reviewed included length-of-stay (LOS), complications, maintenance of patency, continence, and need for additional procedures. RESULTS: Twelve cases of VUAR performed by a single surgeon (BJF) from 2004 to 2012 were identified. Surgical approaches were either abdominal (7), perineal (3), or abdominoperineal (2). All patients underwent prior RP, with 25 % having subsequent radiotherapy. Among patients with stenosis, 43 % were completely obliterated. Two cases had prior anastomotic disruption in the early postoperative period after RP. The median length of stenosis was 2.5 cm (range 1-5 cm) and median LOS was 3.0 days (range 1-7 days). At a median follow-up of 75.5 months (range 14-120 months), 92 % of men retained patency; only 25 % were continent. CONCLUSION: In experienced hands, VUAR can restore durable patency for men afflicted with outlet stenosis after RP. Despite anatomic restoration, incontinence is likely. PMID- 25134945 TI - From extraordinary endocytobionts to pandoraviruses. Comment on Scheid et al.: Some secrets are revealed: parasitic keratitis amoebae as vectors of the scarcely described pandoraviruses to humans. PMID- 25134946 TI - Isolation and molecular characterization of Acanthamoeba and Balamuthia mandrillaris from combination shower units in Costa Rica. AB - Free living amoebae (FLA) are ubiquitous protozoa, which may behave as parasites under certain conditions. Four genera are recognized as causal agents of infections in humans and animals: Naegleria, Sappinia, Acanthamoeba and Balamuthia. This work determines the presence of FLA in combination shower units and employs molecular biology for the characterization of isolates. The morphological analysis and partial sequencing of the 18S rDNA gene revealed the presence of Acanthamoeba genotype T4 in 30% of the units sampled. In addition to Acanthamoeba cysts, trophozoites with morphological characteristics similar to Balamuthia were identified. PCR assay using the mitochondrial 16S rRNA gene as a target confirmed the identification of the amoeba as Balamuthia mandrillaris. Up to date, this is the first report of the isolation of B. mandrillaris in Central America and the fifth report worldwide. PMID- 25134947 TI - Harmonisation of short-term in vitro culture for the expansion of antigen specific CD8(+) T cells with detection by ELISPOT and HLA-multimer staining. AB - Ex vivo ELISPOT and multimer staining are well-established tests for the assessment of antigen-specific T cells. Many laboratories are now using a period of in vitro stimulation (IVS) to enhance detection. Here, we report the findings of a multi-centre panel organised by the Association for Cancer Immunotherapy Immunoguiding Program to investigate the impact of IVS protocols on the detection of antigen-specific T cells of varying ex vivo frequency. Five centres performed ELISPOT and multimer staining on centrally prepared PBMCs from 3 donors, both ex vivo and following IVS. A harmonised IVS protocol was designed based on the best performing protocol(s), which was then evaluated in a second phase on 2 donors by 6 centres. All centres were able to reliably detect antigen-specific T cells of high/intermediate frequency both ex vivo (Phase I) and post-IVS (Phase I and II). The highest frequencies of antigen-specific T cells ex vivo were mirrored in the frequencies following IVS and in the detection rates. However, antigen-specific T cells of a low/undetectable frequency ex vivo were not reproducibly detected post IVS. Harmonisation of the IVS protocol reduced the inter-laboratory variation observed for ELISPOT and multimer analyses by approximately 20 %. We further demonstrate that results from ELISPOT and multimer staining correlated after (P < 0.0001 and R (2) = 0.5113), but not before IVS. In summary, IVS was shown to be a reproducible method that benefitted from method harmonisation. PMID- 25134948 TI - Effect of organic solvents on the structure and activity of moderately halophilic Bacillus sp. EMB9 protease. AB - Halophilic enzymes have been manifested for their stability and catalytic abilities under harsh operational conditions. These have been documented to withstand denaturation in presence of high temperature, pH, presence of organic solvents and chaotropic agents. The present study aims at understanding the stability and activity of a halophilic Bacillus sp. EMB9 protease in organic solvents. The protease was uniquely stable in polar solvents. A clear correlation was evident between the protease function and conformational transitions, validated by CD and fluorescence spectral studies. The study affirms that preservation of protein structure, possibly due to charge screening of the protein surface by Ca(2+) and Na(+) ions provides stability against organic solvents and averts denaturation. Salt was also found to exert a protective effect on dialyzed protease against chaotropism of solvents. Presence of 1 % (w/v) NaCl restored the activity in the dialyzed protease and prevented denaturation in methanol, toluene and n-decane. The work will have further implication on discerning protein folding in saline as well as non-aqueous environments. PMID- 25134949 TI - Competing priorities: staff perspectives on supporting recovery. AB - Recovery has come to mean living a life beyond mental illness, and recovery orientation is policy in many countries. The aims of this study were to investigate what staff say they do to support recovery and to identify what they perceive as barriers and facilitators associated with providing recovery-oriented support. Data collection included ten focus groups with multidisciplinary clinicians (n = 34) and team leaders (n = 31), and individual interviews with clinicians (n = 18), team leaders (n = 6) and senior managers (n = 8). The identified core category was Competing Priorities, with staff identifying conflicting system priorities that influence how recovery-oriented practice is implemented. Three sub-categories were: Health Process Priorities, Business Priorities, and Staff Role Perception. Efforts to transform services towards a recovery orientation require a whole-systems approach. PMID- 25134950 TI - Evaluation of Period of PURPLE Crying, an abusive head trauma prevention program. AB - The Period of PURPLE Crying program is used to educate parents and caregivers about normal infant crying and the dangers of infant shaking. We evaluated nurse led, hospital-based implementation of the program using a nonexperimental, posttest-only design. New mothers rated the program as useful, and the program was effective in teaching mothers about normal infant crying, the dangers of infant shaking, and soothing and coping techniques. The findings support the feasibility and need for broad dissemination of the program. PMID- 25134952 TI - Comparative study of the selective degradations of two enantiomers in the racemate and an enriched concentration of indoxacarb in soils. AB - In this study, selective degradations of the two enantiomers of indoxacarb in the concentrate (2.33S/1R) and racemate (1S/1R) are examined. The absolute configurations of indoxacarb enantiomers were determined using X-ray diffraction. The results showed that in two alkaline soils, the S-(+)-indoxacarb was preferentially degraded in both the concentrate and racemate. In one acid soil, the two enantiomers degraded no-selectivity. In another acid soil and one neutral soil, the R-(-)-indoxacarb was preferentially degraded in both the concentrate and racemate. Indoxacarb enantiomers were configurationally stable in the five soils, and no interconversion was observed during the incubation. Because no significant difference in degradation was observed after samples were sterilized, the observed enantioselectivity may be attributed primarily to microbial activity in soils. The results indicate that the selective degradation behavior was the same for both formulations that were tested. PMID- 25134951 TI - Multidisciplinary intensive education in the hospital improves outcomes for hospitalized heart failure patients in a Japanese rural setting. AB - BACKGROUND: Heart failure (HF) patients living in rural areas have a lack of HF knowledge and poor self-care because of limited medical care access. Multidisciplinary education to improve self-care behavior is indispensable for such patients. The present study evaluated whether intensive inpatient education improved outcomes of hospitalized HF patients in a Japanese rural setting. METHODS: An inpatient HF management program based on multidisciplinary team intervention was applied to hospitalized HF patients in a Japanese rural area. We defined patients treated within the program from May 2009 to April 2011 as the intervention group (n = 144), and those treated with the usual care from May 2006 to April 2009 as the usual care group (n = 133). The composite endpoints of HF hospitalization and all-cause mortality were compared between the two groups. RESULTS: Compared with patients in the usual care group, those in the intervention group more often received the optimal interventions such as discharge use of beta-blockers, cardiac rehabilitation, pre-discharge diagnostic tests, and multidisciplinary intensive education including nurse-led patient education, pharmacist's medication teaching, and dietitian's nutritional guidance (all P < 0.05). The incidence of the composite endpoints significantly decreased after introducing the program (P < 0.001). Among a number of interventions, multidisciplinary intensive education was the most effective intervention to improve the primary outcome (P < 0.001). CONCLUSIONS: Multidisciplinary intensive education is a key strategy for helping improve the outcome for Japanese HF patients in a rural setting. Our data may give a positive impact on the improvement of healthcare system in Japan. PMID- 25134953 TI - Drug-coated balloon angioplasty for drug-eluting stent restenosis: insight from randomized controlled trials. AB - BACKGROUND: The best treatment option for drug-eluting stent (DES) restenosis has not been established. We performed a meta-analysis to assess the clinical efficacy of drug-coated balloon (DCB) for the treatment of DES restenosis. METHODS: Trials were identified through a literature search from January 2005 through April 2014. All randomized controlled trials were eligible for inclusion if they compared DCB with a control treatment (plain old balloon angioplasty [POBA] or DES) in patients with DES restenosis. RESULTS: Five studies and a total of 864 patients were included in this analysis. Most end-points were significantly reduced for DCB compared with the control groups. For major adverse cardiac events, the relative risk (RR) was 0.49 (P = 0.012); for target lesion revascularization, it was 0.50 (P = 0.044); for recurrent restenosis, it was 0.41 (P = 0.002). There was a lower mortality for DCB (RR 0.29; P = 0.017). The incidence of myocardial infarction was numerically lower, but without statistical significance (RR 0.76; P = 0.55). The DCB effect was more pronounced when compared with POBA than when compared with DES. CONCLUSIONS: This meta-analysis showed that DCB was superior to POBA and comparable to DES for treatment of DES restenosis. The findings in this meta-analysis cannot be extrapolated to DCB in general, because all DCB used in trials included was a single brand of paclitaxel coated balloon. PMID- 25134955 TI - New evidence on the relationship between Microsporidia and Fungi: a genome-wide analysis by DarkHorse software. AB - Microsporidia are a group of obligate intracellular eukaryotic parasites that infect a wide variety of species, including humans. Phylogenetic analysis indicates a relationship between the Microsporidia and the Fungi. However, most results are based on the analysis of relatively few genes. DarkHorse analysis involves the transformation of BLAST results into a lineage probability index (LPI) value and allows for the comparison of genes for an entire genome with those of other genomes. Thus, we can see which genes from the microsporidia score most closely based on the LPI with other eukaryotic organisms. In this analysis, we calculated the LPI for each gene from the genomes of 7 Microsporidia, Antonospora locustae, Enterocytozoon bieneusi, Encephalitozoon cuniculi, Encephalitozoon intestinalis, Nosema bombycis, Nosema ceranae, and Nematocida parisii, to analyze the genetic relationships between Microsporidia and other species. It was found that many (91%) genes were most closely correlated with genes from other microsporidial genomes and had the highest mean LPI (0.985), indicating a monophyletic origin of the Microsporidia. In a subsequent analysis, we excluded the other Microsporidia from the analysis to look for relationships before the divergence of Microsporidia, and found that 43% of the microsporidial genes scored highest with fungal genes, and a higher mean LPI was found with Fungi than with other kingdoms, suggesting that Microsporidia is closely related to Fungi at the genomic level. Microsporidial genes were functionally clustered based on the KOG (Eukaryotic COG) database, and the possible lineages for each gene family were discussed in concert with the DarkHorse results. PMID- 25134954 TI - Effects of glucagon-like peptide-1 agents on left ventricular function: systematic review and meta-analysis. AB - BACKGROUND: The cardiovascular safety of many glucagon-like peptide-1 agents (GLP 1 agents) is unclear. In this study, we assess the effects of the GLP-1 agents on left ventricular function in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). METHODS: PubMed, EMBASE, and the Cochrane Library were searched for the relevant publications up to May 2013 without restriction by language. All clinical controlled trials assessing left ventricular function and cardiovascular outcomes with the GLP-1 agents were selected for eligibility. Fourteen trials (415 patients) were identified as eligible between 1966 and 2013. Twelve of the studies were randomized controlled trials (RCT). RESULTS: The results showed that GLP-1 agent treatment in patients with T2DM and/or CVD led to significantly improved regional left ventricular contractile parameters (including peak left systolic tissue velocity and strain) and global left ventricular performance (including stroke volume, ejection fraction, and left ventricular chambers) compared with patients receiving placebo. CONCLUSIONS: GLP 1 agent treatment in T2DM and/or CVD patients is associated with a modest but significant increase in the odds of left ventricular contractile parameters and left ventricular performance compared with patients having received placebo, which may be indicative of additional cardiovascular benefits for these patients. PMID- 25134956 TI - Microbial contamination of power toothbrushes: a comparison of solid-head versus hollow-head designs. AB - PURPOSE: Microbial contamination of manual toothbrushes relative to their design has been documented for decades, citing concern for cross contamination and self infection with microorganisms. A pilot study of different power toothbrushes was conducted, to compare a solid-head brush to 2 hollow-head brushes for residual contamination with commonly occurring oral microorganisms. METHODS: Participants who met inclusion criteria were enrolled and brushed twice daily for 3 weeks with 1 of 3 randomly assigned power toothbrushes. Brush heads were vortexed and cultured using 5 appropriate media for oral microorganisms: anaerobes and facultative microorganisms, yeast and mold, oral streptococci and oral enterococci anaerobes, Porphyromonas gingivalis, and Fusobacterium species. Analysis of covariance was used to compare the brush groups for transformed microbial counts after adjusting for any demographic variables that may have confounded the results. RESULTS: The solid-head power toothbrush was found to have significantly less microbial contamination than either of the 2 hollow-head power toothbrushes for all the bacteria tested and less than 1 of the hollow-head brushes for yeast and mold. CONCLUSION: The solid-head power toothbrush studied had significantly less residual microbial contamination than the 2 hollow-head power toothbrushes after 3 weeks of twice daily brushing with non-antimicrobial toothpaste. PMID- 25134957 TI - The use of social media in dental hygiene programs: a survey of program directors. AB - PURPOSE: The use of social media and social networking sites has become increasingly common by the current generation of students. Colleges and universities are using social media and social networking sites to advertise, engage and recruit prospective students. The purpose of this study was to evaluate how social media is being used in dental hygiene program admissions and policy. METHODS: Researchers developed a survey instrument investigating the use of social media. The survey included questions about demographic information, personal use of social media, program use of social media, social media use in admissions and social media policies. An email was sent to 321 dental hygiene program directors asking them to complete the survey. All participants were provided 4 weeks to complete the survey, and 2 reminder emails were sent. RESULTS: A total of 155 responses were received (48.3% response rate). While 84% of respondents indicated their program had a web page, only 20% had an official Facebook page for the program and 2% had a Twitter page. Thirty-five percent had a program policy specifically addressing the use of social media and 31% indicated that their university or institution had a policy. Only 4% of programs evaluate a potential student's Internet presence, mostly by searching on Facebook. Statistically significant differences (p<=0.05) were noted between those respondents with more personal social media accounts and those with fewer accounts, as those with more accounts were more likely to evaluate a potential student's Internet presence. Open ended responses included concern about social media issues, but some uncertainty on how to handle social media in the program. The concern for social media and professionalism was evident and more research and discussion in this area is warranted. CONCLUSION: Social media is currently being used in a variety of ways in dental hygiene programs, but not in the area of admissions. There is some uncertainty about the role social media should play in a professional environment. PMID- 25134958 TI - Smiles over time: an older adult oral health survey in Illinois. AB - PURPOSE: The purpose of the project was to identify the oral health status and needs of the older adult population >=60 years old in Illinois for policy decisions and to help identify possible need for oral health interventions. No baseline data has previously been collected on this population in Illinois. METHODS: A public/private collaboration was formed, which included the Illinois Department of Public Health, the IFLOSS Coalition and dental and dental hygiene schools in Illinois. The screening tool was developed based on methods outlined by Association of State and Territorial Dental Directors for Basic Screening Surveys. Questionnaires and in-mouth screenings were conducted at selected sites statewide. Data was collected by dental and dental hygiene students and faculty at onsite clinics and community outreach sites. RESULTS: A total of 437 seniors were screened statewide. Of this population, 81% had no dental insurance, 13% were edentulous and 58% claimed to have had a dental visit in the last year.A total of 26% rated their oral health as fair or poor, while 29% had untreated caries. Suspicious oral lesions were present in 14% (n=308 for the oral lesions indicator), 19% needed immediate dental care and 41% required referral. CONCLUSION: This study revealed that surveillance can be accomplished by the collaboration among entities with focus on a specific population. Additional surveillance efforts are warranted among older adults in Illinois in an effort to plan and to implement appropriate interventions for addressing the oral health needs of this population. PMID- 25134960 TI - Effects of motor-level transcutaneous electrical nerve stimulation on ipsilateral and un-stimulated contralateral quadriceps femoris. AB - PURPOSE: There is a paucity of data on effects of motor-level stimulation using Transcutaneous Electrical Nerve Stimulator (TENS) on ipsilateral quadriceps femoris group of muscles. The effect is also unknown on the untrained contralateral quadriceps femoris. The primary purpose of this study was to determine the effect of TENS on quadriceps muscle strength at the stimulated ipsilateral and un-stimulated contra-lateral extremities. METHODS: Participants were 50 apparently healthy undergraduate. They were recruited using sample of convenience. The right quadriceps group of muscles were stimulated for 15 minutes twice a week for 8 weeks using motor-level stimulation parameters (frequency of 85 Hz and pulse width of 100 microseconds) while the left lower limbs (control) were not stimulated. The right and left quadriceps muscle strengths were quantified using tensiometer; at onset and after 8 weeks. The data were analysed using the descriptive and inferential statistics (paired t-test and ANOVA). Alpha level was set at 0.05. RESULTS: The initial and final left strengths of the un stimulated quadriceps muscles were 311.46 +/- 58.84N and 395.60 +/- 100.71N at onset and after 8 weeks respectively. After 8 weeks the un-stimulated left quadriceps strength was significantly greater than the initial value (t=-7.63, p < 0.001). Similarly, the initial and final right quadriceps strength (stimulated limb) were 351.51 +/- 117.68N and 471.31 +/- 112.19N; at onset and after 8 weeks respectively. The post stimulation strength of the right quadriceps was also significantly higher than the pre-intervention strength (t=-10.25, p < 0.001). However, the increment in quadriceps strength between right and left extremities after 8 weeks was insignificant (t =-1.35, p=0.18). There was also significant increase in the girth of the right quadriceps (t= -6.08, p=0.001) after 8 weeks. CONCLUSION: We concluded that there were increments in both strength and muscle size of the stimulated right quadriceps using motor level stimulation parameters of TENS modality. The un-stimulated contralateral quadriceps strength also increased after 8 weeks. This implied that there was cross-training effect at the contralateral quadriceps group of muscles. PMID- 25134959 TI - Identification of drug-resistant Salmonella from food handlers at the University of Gondar, Ethiopia. AB - BACKGROUND: Salmonella species are among the most common food borne pathogens worldwide and their infection is one of the major global public health problems. During the last decade, multidrug-resistant Salmonella species have increased to a great deal, especially in developing countries. The prevalence and antimicrobial susceptibility pattern of Salmonella isolates among food handlers at the University of Gondar, Ethiopia, were described in the current investigation. METHOD: A cross-sectional study was conducted from February to June, 2013 at the University of Gondar. Stool samples from selected volunteer food handlers were collected and analyzed complemented with questionnaire. Standard isolation, identification and biochemical tests were performed to identify Salmonella isolates. Antimicrobial susceptibility tests were also carried out on each isolate using Kirby-Bauer disc diffusion method. The data was entered into Epi info version 3.5.4 and analyzed using SPSS version 21. RESULT: Out of 423 food handlers participated, 303(71.6%) were females. Almost two-third (71.4%) of food handlers had no previous medical checkup to Salmonella infection and only 24(5.7%) of them were certified as food handlers. Thirteen (3.1%) food handlers were found to be positive for Salmonella isolates. The results of antimicrobial susceptibility test in the current research revealed that from a total of 13 isolates; 9(69.2%), 8(61.5%), 6(46.2%) and 6(46.2%) of the isolates were resistant to amoxicillin, ampicillin, nitrofurantoin and tetracycline, respectively. In addition, nearly half (46.2%) of the isolates were multidrug resistant. However; all of them were sensitive for both ceftriaxone and gentamycin. CONCLUSION: This study indicated that drug resistant including multidrug-resistant Salmonella isolates were circulating among food handlers at the University of Gondar. These Salmonella positive food handlers pose significant risk of infection to the university community particularly to the student population. It is essential to implement food handlers training on food safety, conduct periodic medical screening and continuous monitoring of food handlers at the study university. PMID- 25134961 TI - Diagnostic value of bone scintigraphy for aseptic loosening after total knee arthroplasty. AB - BACKGROUND: Despite technical improvements, aseptic loosening after total knee arthroplasty (TKA) remains a frequent complication. A one-stage revision arthroplasty is the most common therapeutic pathway. OBJECTIVE: The aim of this study was to evaluate the diagnostic value of bone scintigraphy in detecting aseptic loosening after TKA. METHODS: We retrospectively identified 46 cases of one-stage revision TKA performed between January 2011 and December 2012. In each case a bone scintigraphy was performed at least one year after the primary TKA and 3.2 +/- 2.2 month prior to revision arthroplasty. Additionally, we evaluated the rate of satisfaction and pain level 16.2 +/- 5.4 months after one-stage revision arthroplasty. RESULTS: Bone scintigraphy indicated aseptic loosening in 28 cases. Intraoperative aseptic loosening was verified in 34 cases. Bone scintigraphy had a sensitivity of 0.76 and a specificity of 0.83 in detecting aseptic loosening. The positive predictive value was 0.93, and the negative predictive value 0.56. At follow-up consultation, 35 patients were very satisfied or satisfied, and 31 patients had no pain or occasional pain. CONCLUSIONS: Bone scintigraphy is a helpful tool in detecting aseptic loosening after TKA. Nevertheless, the results from bone scintigraphy should be compared with clinical findings and patients' disorders. PMID- 25134962 TI - A review on the technologies and services used in the self-management of health and independent living of elderly. AB - As the number of aged people is rapidly growing, the need for health and living care of aged people living alone becomes imperative. The telecare systems are able to provide flexible services for older people suffering from chronic diseases, but are largely user group oriented. However, it is common in elderly to show symptoms of a combination of (chronic) diseases. Moreover, elderly are totally dependent on a third person as they are unable to perform a number of basic functions at home. They also feel cutt off from the social fabric. Old people living in remote places typically use telephone that dials a social alarm control center or mobile social alarm systems and monitoring systems. This study examines the existing solutions related to elderly assistance and proposes an advanced solution based on web technology for the self-management of health and independent living of elderly. PMID- 25134963 TI - Nanomechanical characterization of exfoliated and retained deciduous incisors. AB - OBJECTIVES: The anisotropic natures of dental tissues result in variable properties from one point to the other within the same tooth. The aim of this study was to analyze deciduous incisors enamel and dentin for elastic modulus and hardness. In addition, retained deciduous incisors were assessed to compare properties with exfoliated teeth. METHODS: Deciduous mandibular incisors either exfoliated at physiological age or retained were included in this study. Samples were prepared by dissecting teeth in transverse sections and surfaces under investigation were prepared and polished for nanoindentation. Nanoindentation was performed at multiple sites using Hysitron [TI 725 Ubi] testing instrument. Data analysis was performed using SPSS software (version 20) to calculate absolute hardness and elastic modulus. The statistical significance was calculated using the t-test. RESULTS: The hardness of human deciduous incisor varies between 0.01 7 GPa. The highest value of hardness was observed for the incisal edge (5.09 +/- 0.64 GPa) followed by mid-surface enamel and cervical enamel. The hardness of mantle dentin was (0.56 +/- 0.19 GPa) and the inner dentin was (0.34 +/- 0.12 GPa). CONCLUSIONS: The average hardness of primary teeth enamel is lower than permanent teeth enamel. The hardness of retained teeth enamel is greater than exfoliated teeth however lower than permanent teeth enamel of the equivalent region. PMID- 25134964 TI - Correlation study in respiration fluctuations during sleep stages. AB - BACKGROUND: Healthy sleep can be characterized by several stages: wake, light, SWS, and REM sleep. The clinical experts find that the breath of subjects is different in these sleep stages, but such observation is lacking data supporting, The statistical research about investigating breathing patterns during sleep process will be helpful for the sleep and breathing domain. OBJECTIVE: The objective of the paper is to statistically analyze the respiratory characteristics during different sleep stages. METHODS: Firstly, we calculated the mean value and standard deviation of respiratory rates of these stages, in which the respiratory rates were obtained by the autocorrelation method. Then the detrended fluctuation analysis (DFA) algorithm was applied to analyze long-range correlation of respiratory rates of sleep stages. RESULTS: The mean and standard deviation of respiratory rates are wake: 16.62 +/- 2.43 cycles per minute (CPM), light: 15.15 +/- 1.53 CPM, SWS: 15.06 +/- 0.96 CPM and REM: 16.37 +/- 2.03 CPM, respectively. The scaling exponent applied by detrended fluctuation analysis (DFA) algorithm reached about 0.7 for each stage. CONCLUSION: Results of the mean and standard deviation of respiratory rates show that different sleep stages lead to different autonomic regulations of breathing and exhibit different respiratory rates and fluctuations. And the DFA results demonstrate that respiratory rates are all long-range correlated in these stages although they lead to different fluctuation. PMID- 25134965 TI - In vitro and in vivo characterization of pentaerythritol triacrylate-co trimethylolpropane nanocomposite scaffolds as potential bone augments and grafts. AB - A thiol-acrylate-based copolymer synthesized via an amine-catalyzed Michael addition was studied in vitro and in vivo to assess its potential as an in situ polymerizing graft or augment in bone defect repair. The blends of hydroxyapatite (HA) with pentaerythritol triacrylate-co-trimethylolpropane (PETA), cast as solids or gas foamed as porous scaffolds, were evaluated in an effort to create a biodegradable osteogenic material for use as a bone-void-filling augment. Osteogenesis experiments were conducted with human adipose-derived mesenchymal stromal cells (hASCs) to determine the ability of the material to serve as an osteoinductive substrate. Poly(E-caprolactone) (PCL) composites PCL:HA (80:20) (wt/wt%) served as the control scaffold, while the experimental scaffolds included PETA:HA (100:0), (85:15), (80:20), and (75:25) composites (wt/wt%). The results indicate that PETA:HA (80:20) foam composites had higher mechanical strength than the corresponding porous PCL:HA (80:20) scaffolds made by thermo precipitation method, and in the case of foamed composites, increasing HA content directly correlated with increased yield strength. For cytotoxicity and osteogenesis experiments, hASCs cultured for 21 days on PETA:HA scaffolds in stromal medium displayed the greatest number of live cells compared with PCL:HA composites. Moreover, hASCs cultured on foamed PETA:HA (80:20) scaffolds resulted in the greatest mineralization, increased alkaline phosphatase (ALP) expression, and the highest osteocalcin (OCN) expression after 21 days. Overall, the PETA:HA (80:20) and PETA:HA (85:15) scaffolds, with 66.38% and 72.02% porosity, respectively, had higher mechanical strength and cytocompatibility compared with the PCL:HA control. The results of the 6-week in vivo biocompatibility study using a posterior lumbar spinal fusion model demonstrate that PETA:HA can be foamed in vivo without serious adverse effects at the surgical site. Additionally, it was demonstrated that cells migrate into the interconnected pore volume and are found within centers of ossification. PMID- 25134967 TI - Total calcium-sensing receptor expression in circulating monocytes is increased in rheumatoid arthritis patients with severe coronary artery calcification. AB - INTRODUCTION: Human circulating monocytes express the calcium-sensing receptor (CaSR) and are involved in atherosclerosis. This study investigated the potential association between vascular calcification in rheumatoid arthritis (RA) and CaSR expression in circulating monocytes. METHODS: In this cross-sectional study, 50 RA patients were compared to 25 control subjects matched for age and gender. Isolation of peripheral blood mononuclear cells and flow cytometry analysis were performed to study the surface and total CaSR expression in circulating monocytes. Coronary artery calcium (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography and an association between these scores and the surface and/or total CaSR expression in circulating monocytes in RA patients was investigated. RESULTS: The two groups were similar in terms of age (RA: 60.9 +/- 8.3 years, versus controls: 59.6 +/- 5.3 years) and gender (RA: 74.0% females versus 72.0% females). We did not find a higher prevalence and greater burden of CAC or AAC in RA patients versus age- and gender-matched controls. When compared with control subjects, RA patients did not exhibit greater total CaSR (101.6% +/- 28.8 vs. 99.9% +/- 22.0) or surface CaSR (104.6% +/- 20.4 vs. 99.9% +/- 13.7) expression, but total CaSR expression in circulating monocytes was significantly higher in RA patients with severe CAC (Agatston score >= 200, n = 11) than in patients with mild-to-moderate CAC (1 to 199, n = 21) (P = 0.01). CONCLUSIONS: This study demonstrates for the first time that total CaSR expression in human circulating monocytes is increased in RA patients with severe coronary artery calcification. PMID- 25134966 TI - Relationship between post-cardiac arrest myocardial oxidative stress and myocardial dysfunction in the rat. AB - BACKGROUND: Reperfusion after resuscitation from cardiac arrest (CA) is an event that increases reactive oxygen species production leading to oxidative stress. More specifically, myocardial oxidative stress may play a role in the severity of post-CA myocardial dysfunction. This study investigated the relationship between myocardial oxidative stress and post-CA myocardial injury and dysfunction in a rat model of CA and cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced in 26 rats and was untreated for 6 min. CPR, including mechanical chest compression, ventilation, and epinephrine, was then initiated and continued for additional 6 min prior to defibrillations. Resuscitated animals were sacrificed at two h (n = 9), 4 h (n = 6) and 72 h (n = 8) following resuscitation, and plasma collected for assessment of: high sensitivity cardiac troponin T (hs-cTnT), as marker of myocardial injury; isoprostanes (IsoP), as marker of lipid peroxidation; and 8-hydroxyguanosine (8-OHG), as marker of DNA oxidative damage. Hearts were also harvested for measurement of tissue IsoP and 8 OHG. Myocardial function was assessed by echocardiography at the corresponding time points. Additional 8 rats were not subjected to CA and served as baseline controls. RESULTS: Compared to baseline, left ventricular ejection fraction (LVEF) was reduced at 2 and 4 h following resuscitation (p < 0.01), while it was similar at 72 h. Inversely, plasma hs-cTnT increased, compared to baseline, at 2 and 4 h post-CA (p < 0.01), and then recovered at 72 h. Similarly, plasma and myocardial tissue IsoP and 8-OHG levels increased at 2 and 4 h post-resuscitation (p < 0.01 vs. baseline), while returned to baseline 72 h later. Myocardial IsoP were directly related to hs-cTnT levels (r = 0.760, p < 0.01) and inversely related to LVEF (r = -0.770, p < 0.01). Myocardial 8-OHG were also directly related to hs-cTnT levels (r = 0.409, p < 0.05) and inversely related to LVEF (r = -0.548, p < 0.01). CONCLUSIONS: The present study provides evidence that lipid peroxidation and DNA oxidative damage in myocardial tissue are closely related to myocardial injury and LV dysfunction during the initial hours following CA. PMID- 25134968 TI - The prevalence of dementia subtypes in rural Tanzania. AB - OBJECTIVES: The prevalence of dementia is predicted to increase rapidly in developing countries. Vascular risk factors may contribute to this rise. Our aim was to estimate the proportions of Alzheimer's disease (ADD) and vascular dementia (VAD) in a prevalent cohort of dementia cases in rural Tanzania. DESIGN: A two-stage door-to-door dementia prevalence study. SETTING: Hai district, Tanzania PARTICIPANTS: In Phase I, the Community Screening Instrument for Dementia (CSI-D) was used to screen 1198 community-dwelling people for dementia. In Phase II, 168/184 (91.3%) of those with poor performance, 56/104 (53.8%) of those with intermediate performance and 72/910 (7.9%) of those with good performance on CSI-D were interviewed and diagnoses were made using the DSM-IV criteria. MEASUREMENTS: For subtype diagnosis, DSM-IV dementia criteria plus NINCDS-ADRDA criteria were used for ADD and NINDS-AIREN criteria for VAD. Other dementias were diagnosed by international consensus criteria. Diagnoses were confirmed or excluded by computerised tomography where clinically appropriate. RESULTS: Of 78 dementia cases, 38 (48.7%) were ADD and 32 (41.0%) were VAD. The crude prevalence of ADD was 3.7% (95% CI 2.5 to 4.9) and of VAD was 2.9% (95% CI 1.9 to 3.9). The age-adjusted prevalence was 3.0% (95% CI 1.8 to 4.2) for ADD and 2.6% (95% CI 1.6 to 3.6) for VAD. A previous diagnosis of diabetes mellitus was independently associated with greater odds of having VAD than ADD. CONCLUSIONS: VAD accounted for a greater proportion of dementia cases than expected. Further investigation and treatment of risk factors is required in this setting. PMID- 25134969 TI - Stimulation of suicidal erythrocyte death by sulforaphane. AB - Sulforaphane, an isothiocyanate from cruciferous vegetable, counteracts malignancy. The effect is at least in part due to the stimulation of suicidal death or apoptosis of tumour cells. Mechanisms invoked in sulforaphane-induced apoptosis include mitochondrial depolarization and altered gene expression. Despite the lack of mitochondria and nuclei, erythrocytes may, similar to apoptosis of nucleated cells, enter eryptosis, a suicidal cell death characterized by cell shrinkage and phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca(2+)-activity ([Ca(2+)]i). This study explored whether sulforaphane stimulates eryptosis. Cell volume was estimated from forward scatter, phosphatidylserine exposure at the cell surface from annexin V binding and [Ca(2+)]i from Fluo-3 fluorescence. A 48-hr treatment of human erythrocytes with sulforaphane (50-100 MUM) significantly decreased forward scatter, significantly increased the percentage of annexin V binding cells and significantly increased [Ca(2+)]i. The effect of sulforaphane (100 MUM) on annexin V binding was significantly blunted but not abrogated by the removal of extracellular Ca(2+). Sulforaphane (100 MUM) significantly increased ceramide formation. In conclusion, sulforaphane stimulates suicidal erythrocyte death or eryptosis, an effect at least partially, but not exclusively, due to the stimulation of Ca(2+) entry and ceramide formation. PMID- 25134970 TI - Phenotyping polyclonal kappa and lambda light chain molecular mass distributions in patient serum using mass spectrometry. AB - We previously described a microLC-ESI-Q-TOF MS method for identifying monoclonal immunoglobulins in serum and then tracking them over time using their accurate molecular mass. Here we demonstrate how the same methodology can be used to identify and characterize polyclonal immunoglobulins in serum. We establish that two molecular mass distributions observed by microLC-ESI-Q-TOF MS are from polyclonal kappa and lambda light chains using a combination of theoretical molecular masses from gene sequence data and the analysis of commercially available purified polyclonal IgG kappa and IgG lambda from normal human serum. A linear regression comparison of kappa/lambda ratios for 74 serum samples (25 hypergammaglobulinemia, 24 hypogammaglobulinemia, 25 normal) determined by microflowLC-ESI-Q-TOF MS and immunonephelometry had a slope of 1.37 and a correlation coefficient of 0.639. In addition to providing kappa/lambda ratios, the same microLC-ESI-Q-TOF MS analysis can determine the molecular mass for oligoclonal light chains observed above the polyclonal background in patient samples. In 2 patients with immune disorders and hypergammaglobulinemia, we observed a skewed polyclonal molecular mass distribution which translated into biased kappa/lambda ratios. Mass spectrometry provides a rapid and simple way to combine the polyclonal kappa/lambda light chain abundance ratios with the identification of dominant monoclonal as well as oligoclonal light chain immunoglobulins. We anticipate that this approach to evaluating immunoglobulin light chains will lead to improved understanding of immune deficiencies, autoimmune diseases, and antibody responses. PMID- 25134974 TI - Halogen bonds in crystal engineering: like hydrogen bonds yet different. AB - The halogen bond is an attractive interaction in which an electrophilic halogen atom approaches a negatively polarized species. Short halogen atom contacts in crystals have been known for around 50 years. Such contacts are found in two varieties: type I, which is symmetrical, and type II, which is bent. Both are influenced by geometric and chemical considerations. Our research group has been using halogen atom interactions as design elements in crystal engineering, for nearly 30 years. These interactions include halogen...halogen interactions (X...X) and halogen...heteroatom interactions (X...B). Many X...X and almost all X...B contacts can be classified as halogen bonds. In this Account, we illustrate examples of crystal engineering where one can build up from previous knowledge with a focus that is provided by the modern definition of the halogen bond. We also comment on the similarities and differences between halogen bonds and hydrogen bonds. These interactions are similar because the protagonist atoms halogen and hydrogen-are both electrophilic in nature. The interactions are distinctive because the size of a halogen atom is of consequence when compared with the atomic sizes of, for example, C, N, and O, unlike that of a hydrogen atom. Conclusions may be drawn pertaining to the nature of X...X interactions from the Cambridge Structural Database (CSD). There is a clear geometric and chemical distinction between type I and type II, with only type II being halogen bonds. Cl/Br isostructurality is explained based on a geometric model. In parallel, experimental studies on 3,4-dichlorophenol and its congeners shed light on the nature of halogen...halogen interactions and reveal the chemical difference between Cl and Br. Variable temperature studies also show differences between type I and type II contacts. In terms of crystal design, halogen bonds offer a unique opportunity in the strength, atom size and interaction gradation; this may be used in the design of ternary cocrystals. Structural modularity in which an entire crystal structure is defined as a combination of modules is rationalized on the basis of the intermediate strength of a halogen bond. The specific directionality of the halogen bond makes it a good tool to achieve orthogonality in molecular crystals. Mechanical properties can be tuned systematically by varying these orthogonally oriented halogen...halogen interactions. In a further development, halogen bonds are shown to play a systematic role in organization of LSAMs (long range synthon aufbau module), which are bigger structural units containing multiple synthons. With a formal definition in place, this may be the right time to look at differences between halogen bonds and hydrogen bonds and exploit them in more subtle ways in crystal engineering. PMID- 25134972 TI - Efficacy of dronedarone versus propafenone in the maintenance of sinus rhythm in patients with atrial fibrillation after electrical cardioversion. AB - PURPOSE: Our objective was to compare the efficacy of dronedarone and propafenone in maintaining sinus rhythm in patients with atrial fibrillation (AF) after electrical cardioversion. METHODS: In this single-center, open-label, randomized trial, we randomly assigned patients with AF after electrical cardioversion to receive dronedarone 400 mg BID or propafenone 150 mg TID. Follow-up clinical evaluations were conducted at 1, 2, 3, and 6 months of treatment. The primary end point was the time to the first recurrence of AF. FINDINGS: A total of 98 patients were enrolled (79 men; mean age, 59.2 years; n = 49 per group). The median times to first recurrence of AF were 31 days in the dronedarone group and 32 days in the propafenone group (P = 0.715). The median (interquartile range) ventricular rates at first recurrence of AF were 76.5 (67.3-86.5) beats/min in the dronedarone group and 83.0 (71.0-96.0) beats/min in the propafenone group (P = 0.059). IMPLICATIONS: Dronedarone and propafenone had similar efficacies in maintaining sinus rhythm in patients with AF after electrical cardioversion. The ventricular rate at the first recurrence of AF was numerically but not statistically significantly lower in the dronedarone group than in the propafenone group. ClinicalTrials.gov identifier: NCT01991119. PMID- 25134973 TI - In vitro evaluation of the inhibitory effect of canine serum, canine fresh frozen plasma, freeze-thaw-cycled plasma, and SolcoserylTM on matrix metalloproteinases 2 and 9. AB - OBJECTIVE: Compare the efficacy of canine serum, fresh frozen plasma (FFP), freeze-thaw-cycled plasma (FTCP), and Solcoseryl(TM) at inhibiting matrix metalloproteinases (MMP) 2 and 9 in vitro. PROCEDURE: Matrix metalloproteinases 2 and 9 activity in the presence of serum, FFP, FTCP, or Solcoseryl(TM) was assayed using a commercially available fluorogenic gelatinase activity kit. RESULTS: Matrix metalloproteinases 2 activity in the presence of serum, FFP, FTCP, and Solcoseryl(TM) was 20.84%, 5.76%, 8.10%, and 83.03%, respectively of uninhibited MMP 2 activity. MMP 9 activity in the presence of serum, FFP, FTCP, and Solcoseryl(TM) was 57.36%, 58.35%, 49.35%, and -8.69%, respectively of uninhibited MMP 9 activity. CONCLUSION: Serum, FFP, and FTCP exhibit similar levels of MMP 2 and 9 inhibitions. Solcoseryl(TM) causes minimal MMP 2 inhibition, but profound MMP 9 inhibition. PMID- 25134971 TI - Sex differences in T cells in hypertension. AB - PURPOSE: Hypertension is a major risk factor for cardiovascular disease, stroke, and end-organ damage. There is a sex difference in blood pressure (BP) that begins in adolescence and continues into adulthood, in which men have a higher prevalence of hypertension compared with women until the sixth decade of life. Less than 50% of hypertensive adults in the United States manage to control their BP to recommended levels using current therapeutic options, and women are more likely than are men to have uncontrolled high BP. This, is despite the facts that more women compared with men are aware that they have hypertension and that women are more likely to seek treatment for the disease. Novel therapeutic targets need to be identified in both sexes to increase the percentage of hypertensive individuals with controlled BP. The purpose of this article was to review the available literature on the role of T cells in BP control in both sexes, and the potential therapeutic application/implications of targeting immune cells in hypertension. METHODS: A search of PubMed was conducted to determine the impact of sex on T cell-mediated control of BP. The search terms included sex, gender, estrogen, testosterone, inflammation, T cells, T regulatory cells, Th17 cells, hypertension, and blood pressure. Additional data were included from our laboratory examinations of cytokine expression in the kidneys of male and female spontaneously hypertensive rats (SHRs) and differential gene expression in both the renal cortex and mesenteric arterial bed of male and female SHRs. FINDINGS: There is a growing scientific literature base regarding the role of T cells in the pathogenesis of hypertension and BP control; however, the majority of these studies have been performed exclusively in males, despite the fact that both men and women develop hypertension. There is increasing evidence that although T cells also mediate BP in females, there are distinct differences in both the T cell profile and the functional impact of sex differences in T cells on cardiovascular health, although more work is needed to better define the relative impact of different T-cell subtypes on BP in both sexes. IMPLICATIONS: The challenge now is to fully understand the molecular mechanisms by which the immune system regulates BP and how the different components of the immune system interact so that specific mechanisms can be targeted therapeutically without compromising natural immune defenses. PMID- 25134975 TI - Dimensionality control of d-orbital occupation in oxide superlattices. AB - Manipulating the orbital state in a strongly correlated electron system is of fundamental and technological importance for exploring and developing novel electronic phases. Here, we report an unambiguous demonstration of orbital occupancy control between t2g and eg multiplets in quasi-two-dimensional transition metal oxide superlattices (SLs) composed of a Mott insulator LaCoO3 and a band insulator LaAlO3. As the LaCoO3 sublayer thickness approaches its fundamental limit (i.e. one unit-cell-thick), the electronic state of the SLs changed from a Mott insulator, in which both t2g and eg orbitals are partially filled, to a band insulator by completely filling (emptying) the t2g (eg) orbitals. We found the reduction of dimensionality has a profound effect on the electronic structure evolution, which is, whereas, insensitive to the epitaxial strain. The remarkable orbital controllability shown here offers a promising pathway for novel applications such as catalysis and photovoltaics, where the energy of d level is an essential parameter. PMID- 25134976 TI - Dopamine D1 receptor availability is related to social behavior: a positron emission tomography study. AB - Dysfunctional interpersonal behavior is thought to underlie a wide spectrum of psychiatric disorders; however, the neurobiological underpinnings of these behavioral disturbances are poorly understood. Previous molecular imaging studies have shown associations between striatal dopamine (DA) D2-receptor binding and interpersonal traits, such as social conformity. The objective of this study was to explore, for the first time, the role of DA D1-receptors (D1-Rs) in human interpersonal behavior. Twenty-three healthy subjects were examined using positron emission tomography and the radioligand [(11)C]SCH23390, yielding D1-R binding potential values. Striatal D1-R binding was related to personality scales selected to specifically assess one dimension of interpersonal behavior, namely a combination of affiliation and dominance (i.e., the Social Desirability, Verbal Trait Aggression and Physical Trait Aggression scales from Swedish Universities Scales of Personality). An exploratory analysis was also performed for extrastriatal brain regions. D1-R binding potential values in the limbic striatum (r = .52; p = .015), associative striatum (r = .55; p = .009), and sensorimotor striatum (r = .67; p = .001) were positively related to Social Desirability scores. D1-R binding potential in the limbic striatum (r = -.51; p = .019) was negatively associated with Physical Trait Aggression scores. For extrastriatal regions, Social Desirability scores showed positive correlations in the amygdala (r = .60; p = .006) and medial frontal cortex (r = .60; p = .004). This study provides further support for the role of DA function in the expression of disaffiliative and dominant traits. Specifically, D1-R availability may serve as a marker for interpersonal behavior in humans. Associations were demonstrated for the same dimension of interpersonal behavior as for D2-R, but in the opposite direction, suggesting that the two receptor subtypes are involved in the same behavioral processes, but with different functional roles. PMID- 25134977 TI - Automated tract extraction via atlas based Adaptive Clustering. AB - Advancements in imaging protocols such as the high angular resolution diffusion weighted imaging (HARDI) and in tractography techniques are expected to cause an increase in the tract-based analyses. Statistical analyses over white matter tracts can contribute greatly towards understanding structural mechanisms of the brain since tracts are representative of connectivity pathways. The main challenge with tract-based studies is the extraction of the tracts of interest in a consistent and comparable manner over a large group of individuals without drawing the inclusion and exclusion regions of interest. In this work, we design a framework for automated extraction of white matter tracts. The framework introduces three main components, namely a connectivity based fiber representation, a fiber bundle atlas, and a clustering approach called Adaptive Clustering. The fiber representation relies on the connectivity signatures of fibers to establish an easy correspondence between different subjects. A group wise clustering of these fibers that are represented by the connectivity signatures is then used to generate a fiber bundle atlas. Finally, Adaptive Clustering incorporates the previously generated clustering atlas as a prior, to cluster the fibers of a new subject automatically. Experiments on the HARDI scans of healthy individuals acquired repeatedly, demonstrate the applicability, reliability and the repeatability of our approach in extracting white matter tracts. By alleviating the seed region selection and the inclusion/exclusion ROI drawing requirements that are usually handled by trained radiologists, the proposed framework expands the range of possible clinical applications and establishes the ability to perform tract-based analyses with large samples. PMID- 25134979 TI - Impact of comorbidity, age, and gender on seasonal variation in hip fracture incidence. A NOREPOS study. AB - Based on a total of 136,140 hip fractures, we found a distinct seasonal variation in hip fracture incidence present in subgroups defined by age, gender, and comorbidity. The seasonal variation was most pronounced in the youngest and the healthiest patients. PURPOSE: The purpose of this study was to examine the possible seasonal variation in hip fracture incidence in Norway by comorbidity, age, and gender. METHODS: Data were retrieved from the NOREPOS Hip Fracture Database containing all hip fractures in Norway during the time period 1994-2008. Hip fractures were identified by computerized hospital discharge diagnoses. Charlson comorbidity index was calculated based on additional diagnoses and categorized (0, 1, and >=2). Summer was defined as June, July, and August and winter as December, January, and February. Incidence rate ratios for hip fracture according to season were calculated by negative binomial models. RESULTS: In patients aged 50-103 years, 136,140 eligible fractures were identified (72.5 % women). The relative risk of hip fracture in winter versus summer was 1.40 (95 % confidence interval (CI) 1.36-1.45) in men and 1.26 (95 % CI 1.23-1.28) in women. June had the lowest number of fractures in both genders. We found seasonal variation in all subgroups by age and gender, although least pronounced in patients >79 years. There was a significant interaction between season and comorbidity (p = 0.022). When comparing winter to summer, we found relative risks of 1.40 (95 % CI 1.31-1.50) in patients with Charlson index = 0, 1.29 (95 % CI 1.19-1.40) in patients with Charlson index = 1, and 1.18 (95 % CI 1.08-1.28) in patients with Charlson index >=2. CONCLUSIONS: There was a distinct seasonal variation in hip fracture incidence, present in all subgroups of gender, age, or comorbidity. This variation should be accounted for when planning health-care services. PMID- 25134978 TI - Optimising beamformer regions of interest analysis. AB - Beamforming is a spatial filtering based source reconstruction method for EEG and MEG that allows the estimation of neuronal activity at a particular location within the brain. The computation of the location specific filter depends solely on an estimate of the data covariance matrix and on the forward model. Increasing the number of M/EEG sensors, increases the quantity of data required for accurate covariance matrix estimation. Often however we have a prior hypothesis about the site of, or the signal of interest. Here we show how this prior specification, in combination with optimal estimations of data dimensionality, can give enhanced beamformer performance for relatively short data segments. Specifically we show how temporal (Bayesian Principal Component Analysis) and spatial (lead field projection) methods can be combined to produce improvements in source estimation over and above employing the approaches individually. PMID- 25134980 TI - Women's perspectives and experiences on screening for osteoporosis (Risk stratified Osteoporosis Strategy Evaluation, ROSE). AB - This study aimed to investigate women's perspectives and experiences with screening for osteoporosis. Focus groups and individual interviews were conducted. Three main themes emerged: knowledge about osteoporosis, psychological aspects of screening, and moral duty. Generally, screening was accepted due to life experiences, self-perceived risk, and the preventive nature of screening. PURPOSE: The risk-stratified osteoporosis strategy evaluation (ROSE) study is a randomized prospective population-based trial investigating the efficacy of a screening program to prevent fractures in women aged 65-80 years. It is recommended by the World Health Organization that a set of criteria are met before a screening program is implemented. This sub-study aims to investigate women's perspectives and experiences with the ROSE screening program in relation to the patient-related criteria recommended by the World Health Organization. METHODS: A qualitative study was carried out involving 31 women by way of 8 focus group interviews and 11 individual interviews. Principles from critical psychology guided the analysis. RESULTS: Women's perspectives and experiences with the screening program were described by three main themes: knowledge about osteoporosis, psychological aspects of screening, and moral duty. The women viewed the program in the context of their everyday life and life trajectories. Age, lifestyle, and knowledge about osteoporosis were important to how women ascribed meaning to the program, how they viewed the possibilities and limitations, and how they rationalized their actions and choices. The women displayed limited knowledge about osteoporosis and its risk factors. However, acceptance was based on prior experience, perceived risk, and evaluation of preventive measures. To be reassured or concerned by screening was described as important issues, as well as the responsibility for health-seeking behaviour. CONCLUSION: In general, the women accepted the screening program. No major ethical reservations or adverse psychological consequences were detected. Only a minority of women declined screening participation due to a low perceived risk of osteoporosis. PMID- 25134981 TI - Transcatheter valve-in-valve implantation for degenerated mitral valve bioprosthesis under 3D echocardiographic guidance. AB - Transcatheter mitral valve-in-valve replacement is increasingly being performed as operator and center experience in transcatheter valve replacement technology and techniques have accrued. Complications, such as valve embolization and paravalvular regurgitation, still occur and relate to valve deployment. The use of novel imaging techniques, such as 3D echocardiography, allows for better differentiation of cardiac structures and appropriate positioning of the transcatheter valve using well-visualized anatomical landmarks. Here the authors describe in images and video the use of 3D echocardiography for deployment of a mitral valve-in-valve. PMID- 25134982 TI - Pregnant couples at increased risk for common aneuploidies choose maximal information from invasive genetic testing. AB - Genomic array detects more pathogenic chromosome aberrations than conventional karyotyping (CK), including genetic variants associated with a susceptibility for neurodevelopmental disorders; susceptibility loci (SL). Consensus regarding the scope of invasive prenatal diagnosis (PND) pregnant couples should be offered is lacking. This study examined pregnant couples' preferences, doubts and satisfaction regarding the scope of invasive PND. Eighty-two couples choosing prenatal screening (PNS) and 59 couples choosing invasive PND were offered a choice between 5 (comparable to CK) and 0.5 Mb resolution array analysis outcomes, the latter with or without reporting SL. A pre-test self-report questionnaire and post-test telephone interview assessed their choices in-depth. Actual (PND) and hypothetical (PNS) choices differed significantly (p < 0.001). Ninety-five percent of the couples in the PND group chose 0.5 Mb array, vs 69% in the PNS group. Seven percent of the PND group wished not to be informed of SL. Ninety percent was satisfied with their choice and wished to decide about the scope themselves. Pregnant couples wish to make their own choices regarding the scope of invasive PND. It therefore seems justified to offer them a choice in both the resolution of array and disclosure of SL. PMID- 25134983 TI - Cytotoxicity of purified listeriolysin O on mouse and human leukocytes and leukaemia cells. AB - BACKGROUND: Listeriolysin O (LLO) is the main virulence factor of Listeria monocytogenes and facilitates the intracellular survival of the pathogen. Some of its characteristics endorse the growing popularity of LLO for use in biotechnology, particularly in the development of novel vaccines. Here, we evaluate the use of LLO to eradicate leukaemia cells. RESULTS: A purified LLO preparation was obtained by affinity chromatography. The LLO preparation procedure was optimized and purified LLO was tested for optimal conditions of storage including temperature, application of proteinase inhibitors and serum components. We demonstrated the possibility of regulating LLO activity by adjusting cell membrane cholesterol content. The LLO preparation had haemolytic activity and had a cytotoxic effect on the human T-leukaemia Jurkat cell line as well as mouse and human peripheral blood mononuclear cells. CONCLUSIONS: LLO has a very potent cytotoxic activity towards human leukocytes. Importantly, the cytotoxic activity was easily regulated in vitro and could be restricted to areas containing malignant cells, raising the possibility of future clinical application of LLO for leukaemia treatment. PMID- 25134985 TI - A systematic review evaluating the impact of online or blended learning vs. face to-face learning of clinical skills in undergraduate nurse education. AB - AIM: To determine whether the use of an online or blended learning paradigm has the potential to enhance the teaching of clinical skills in undergraduate nursing. BACKGROUND: The need to adequately support and develop students in clinical skills is now arguably more important than previously considered due to reductions in practice opportunities. Online and blended teaching methods are being developed to try and meet this requirement, but knowledge about their effectiveness in teaching clinical skills is limited. DESIGN: Mixed methods systematic review, which follows the Joanna Briggs Institute User guide version 5. DATA SOURCES: Computerized searches of five databases were undertaken for the period 1995-August 2013. REVIEW METHODS: Critical appraisal and data extraction were undertaken using Joanna Briggs Institute tools for experimental/observational studies and interpretative and critical research. A narrative synthesis was used to report results. RESULTS: Nineteen published papers were identified. Seventeen papers reported on online approaches and only two papers reported on a blended approach. The synthesis of findings focused on the following four areas: performance/clinical skill, knowledge, self efficacy/clinical confidence and user experience/satisfaction. The e-learning interventions used varied throughout all the studies. CONCLUSION: The available evidence suggests that online learning for teaching clinical skills is no less effective than traditional means. Highlighted by this review is the lack of available evidence on the implementation of a blended learning approach to teaching clinical skills in undergraduate nurse education. Further research is required to assess the effectiveness of this teaching methodology. PMID- 25134986 TI - Hereditary angioedema with F12 mutation: factors modifying the clinical phenotype. AB - BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (C1Inh) associated with the c.983C>A and c.983C>G mutations of the F12 gene (FXII-HAE) is a rare condition, and presents with highly variable clinical expression. On the basis of data gathered from a large carrier cohort, we assessed the modifiers affecting the clinical phenotype. METHODS: We analyzed clinical and biological data recorded from 118 mutation carriers (80 symptomatic and 38 asymptomatic), 58 noncarrier relatives from 40 families, and 200 healthy donors. Disease severity was scored in relation to frequency and location of edema, as well as age at disease onset. To predict FXII-HAE disease severity, we analyzed the biological phenotype [C1Inh, C4, spontaneous amidase, angiotensin-I-converting enzyme (ACE), aminopeptidase P (APP), and carboxypeptidase N/M (CPN)] by means of logistic regression (Akaike information criterion) and odds ratio (OR). RESULTS: Meaningful variables contributed to FXII-HAE, with the kinin catabolism enzymes ACE and CPN exhibiting a significant inverse relationship with disease severity (OR = 0.36, 95% CI 0.23-0.59, P < 0.001; OR = 0.58, 95% CI 0.36-0.91, P < 0.05, respectively). CPN activities were 37.5 (28.5-41.3) nmol/ml/min and 38.5 (32.8 45.6) for FXII-HAE asymptomatic and symptomatic carriers, respectively, and 37.9 (30.5-43.7) nmol/ml/min for noncarriers. Angiotensin-I-converting enzyme activities were 58 (44-76) and 49 (35-59) nmol/ml/min for FXII-HAE asymptomatic and symptomatic carriers, respectively, and 56 (49-66) nmol/ml/min for noncarriers. CONCLUSIONS: The FXII-HAE is associated with modifiers, for example kinin catabolism enzymes, ACE and CPN, different from those recognized in HAE with C1Inh deficiency. PMID- 25134987 TI - The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells. AB - CYLD is a tumour suppressor gene mutated in familial cylindromatosis, a genetic disorder leading to the development of skin appendage tumours. It encodes a deubiquitinating enzyme that removes Lys63- or linear-linked ubiquitin chains. CYLD was shown to regulate cell proliferation, cell survival and inflammatory responses, through various signalling pathways. Here we show that CYLD localizes at centrosomes and basal bodies via interaction with the centrosomal protein CAP350 and demonstrate that CYLD must be both at the centrosome and catalytically active to promote ciliogenesis independently of NF-kappaB. In transgenic mice engineered to mimic the smallest truncation found in cylindromatosis patients, CYLD interaction with CAP350 is lost disrupting CYLD centrosome localization, which results in cilia formation defects due to impairment of basal body migration and docking. These results point to an undiscovered regulation of ciliogenesis by Lys63 ubiquitination and provide new perspectives regarding CYLD function that should be considered in the context of cylindromatosis. PMID- 25134988 TI - Should electric fans be used during a heat wave? AB - Heat waves continue to claim lives, with the elderly and poor at greatest risk. A simple and cost-effective intervention is an electric fan, but public health agencies warn against their use despite no evidence refuting their efficacy in heat waves. A conceptual human heat balance model can be used to estimate the evaporative requirement for heat balance, the potential for evaporative heat loss from the skin, and the predicted sweat rate, with and without an electrical fan during heat wave conditions. Using criteria defined by the literature, it is clear that fans increase the predicted critical environmental limits for both the physiological compensation of endogenous/exogenous heat, and the onset of cardiovascular strain by an air temperature of ~3-4 degrees C, irrespective of relative humidity (RH) for the young and elderly. Even above these critical limits, fans would apparently still provide marginal benefits at air temperatures as high as 51.1 degrees C at 10%RH for young adults and 48.1 degrees C at 10%RH for the elderly. Previous concerns that dehydration would be exacerbated with fan use do not seem likely, except under very hot (>40 degrees C) and dry (<10%RH) conditions, when predicted sweat losses are only greater with fans by a minor amount (~20-30 mL/h). Relative to the peak outdoor environmental conditions reported during ten of the most severe heat waves in recent history, fan use would be advisable in all of these situations, even when reducing the predicted maximum sweat output for the elderly. The protective benefit of fans appears to be underestimated by current guidelines. PMID- 25134990 TI - Efficient ammonium uptake and mobilization of vacuolar arginine by Saccharomyces cerevisiae wine strains during wine fermentation. AB - BACKGROUND: Under N-limiting conditions, Saccharomyces cerevisiae strains display a substantial variability in their biomass yield from consumed nitrogen -in particular wine yeasts exhibit high growth abilities- that is correlated with their capacity to complete alcoholic fermentation, a trait of interest for fermented beverages industries. The aim of the present work was to assess the contribution of nitrogen availability to the strain-specific differences in the ability to efficiently use N-resource for growth and to identify the underlying mechanisms. We compared the profiles of assimilation of several nitrogen sources (mostly ammonium, glutamine, and arginine) for high and low biomass-producing strains in various conditions of nitrogen availability. We also analyzed the intracellular fate of nitrogen compounds. RESULTS: Strains clustered into two groups at initial nitrogen concentrations between 85 and 385 mg N.L(-1): high biomass producers that included wine strains, were able to complete fermentation of 240 g.L(-1) glucose and quickly consume nitrogen, in contrast to low biomass producers. The two classes of strains exhibited distinctive characteristics that contributed to their differential capacity to produce biomass. The contribution of each characteristic varied according to nitrogen availability. In high biomass producers, the high rate of ammonium uptake resulted in an important consumption of this preferred nitrogen source that promoted the growth of these yeasts when nitrogen was provided in excess. Both classes of yeast accumulated poor nitrogen sources, mostly arginine, in vacuoles during the first stages of growth. However, at end of the growth phase when nitrogen had become limiting, high biomass producers more efficiently used this vacuolar nitrogen fraction for protein synthesis and further biomass formation than low biomass producers. CONCLUSIONS: Overall, we demonstrate that the efficient management of the nitrogen resource, including efficient ammonium uptake and efficient use of the amino acids stored in vacuoles during the late stages of growth, might lead to high biomass production by wine yeasts. PMID- 25134991 TI - Reduced intraocular pressure after cataract surgery in patients with narrow angles and chronic angle-closure glaucoma. AB - PURPOSE: To evaluate the effect of cataract surgery on intraocular pressure (IOP) in patients with narrow angles and chronic angle-closure glaucoma (ACG) and to determine whether the change in IOP was correlated with the preoperative pressure, axial length (AL), and anterior chamber depth (ACD). SETTING: Private practice, Atlanta, Georgia, USA. DESIGN: Retrospective case series. METHODS: Charts of patients with narrow angles or chronic ACG who had cataract surgery were reviewed. All eyes had previous laser iridotomies. Data recorded included preoperative and postoperative IOP, AL, and ACD. The preoperative IOP was used to stratify eyes into 4 groups. RESULTS: The charts of 56 patients (83 eyes) were reviewed. The mean reduction IOP in all eyes was 3.28 mm Hg (18%), with 88% having a decrease in IOP. There was a significant correlation between preoperative IOP and the magnitude of IOP reduction (r = 0.68, P < .001). The mean decrease in IOP was 5.3 mm Hg in eyes with a preoperative IOP above 20 mm Hg, 4.6 mm Hg in the over 18 to 20 mm Hg group, 2.5 mm Hg in the over 15 to 18 mm Hg group, and 1.4 mm Hg in the 15 mm Hg or less group. The mean follow-up was 3.0 years +/- 2.3 (SD). CONCLUSIONS: Cataract surgery reduced IOP in patients with narrow angles and chronic ACG. The magnitude of reduction was highly correlated with preoperative IOP and weakly correlated with ACD. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25134989 TI - Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4 mediated inflammatory monocyte migration. AB - Inflammatory monocytes play an important role in host defense against infections. However, the regulatory mechanisms of transmigration into infected tissue are not yet completely understood. Here we show that mice deficient in MAIR-II (also called CLM-4 or LMIR2) are more susceptible to caecal ligation and puncture (CLP) induced peritonitis than wild-type (WT) mice. Adoptive transfer of inflammatory monocytes from WT mice, but not from MAIR-II, TLR4 or MyD88-deficient mice, significantly improves survival of MAIR-II-deficient mice after CLP. Migration of inflammatory monocytes into the peritoneal cavity after CLP, which is dependent on VLA-4, is impaired in above mutant and FcRgamma chain-deficient mice. Lipopolysaccharide stimulation induces association of MAIR-II with FcRgamma chain and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1. These results indicate that activation of MAIR-II/FcRgamma chain by TLR4/MyD88-mediated signalling is essential for the transmigration of inflammatory monocytes from the blood to sites of infection mediated by VLA-4. PMID- 25134992 TI - Comparison of the metal-to-ceramic bond strengths of four noble alloys with press on-metal and conventional porcelain layering techniques. AB - STATEMENT OF PROBLEM: New noble alloys for metal ceramic restorations introduced by manufacturers are generally lower-cost alternatives to traditional higher-gold alloys. Information about the metal-to-ceramic bond strength for these alloys, which is needed for rational clinical selection, is often lacking. PURPOSE: The purpose of this study was to evaluate the bond strength of 4 recently introduced noble alloys by using 2 techniques for porcelain application. MATERIAL AND METHODS: Aquarius Hard (high-gold: 86.1 gold, 8.5 platinum, 2.6 palladium, 1.4 indium; values in wt. %), Evolution Lite (reduced-gold: 40.3 gold, 39.3 palladium, 9.3 indium, 9.2 silver, 1.8 gallium), Callisto 75 Pd (palladium-silver containing gold: 75.2 palladium, 7.1 silver, 2.5 gold, 9.3 tin, 1.0 indium), and Aries, (conventional palladium-silver: 63.7 palladium, 26.0 silver, 7.0 tin, 1.8 gallium, 1.5 indium) were selected for bonding to leucite-containing veneering porcelains. Ten metal ceramic specimens that met dimensional requirements for International Organization for Standardization (ISO) Standard 9693 were prepared for each alloy by using conventional porcelain layering and press-on-metal methods. The 3-point bending test in ISO Standard 9693 was used to determine bond strength. Values were compared with 2-way ANOVA (maximum likelihood analysis, SAS Mixed Procedure) and the Tukey test (alpha=.05). RESULTS: Means (standard deviations) for bond strength with conventional porcelain layering were as follows: Aquarius Hard (50.7 +/-5.5 MPa), Evolution Lite (40.2 +/-3.3 MPa), Callisto 75 Pd (37.2 +/-3.9 MPa), and Aries (34.0 +/-4.9 MPa). For the press-on metal technique, bond strength results were as follows: Aquarius Hard (33.7 +/ 11.5 MPa), Evolution Lite (34.9 +/-4.5 MPa), Callisto 75 Pd (37.2 +/-11.9 MPa), and Aries (30.7 +/-10.8 MPa). From statistical analyses, the following 3 significant differences were found for metal-to-ceramic bond strength: the bond strength for Aquarius Hard was significantly higher for conventional porcelain layers compared with the press-on-metal technique; the bond strength for Aquarius Hard with conventional porcelain layers was significantly higher than the bond strengths for the other 3 alloys with conventional porcelain layers; and the bond strength for Aquarius Hard with conventional porcelain layers was significantly higher than the bond strength for Callisto 75 Pd with conventional porcelain layers and the other 3 alloys with the press-on-metal technique. CONCLUSIONS: For both conventional layering and press-on-metal techniques, all 4 noble alloys had a mean metal-to-ceramic bond strength that substantially exceeded the 25 MPa minimum in the ISO Standard 9693. The results for Aries support the manufacturer's recommendation not to use the press-on-metal technique for alloys that contain more than 10% silver. PMID- 25134993 TI - Evaluating the ability of dental technician students and graduate dentists to match tooth color. AB - STATEMENT OF PROBLEM: The ability of dental technician students to match tooth shade with the Vita 3D-Master shade guide and Toothguide Training Box has not been investigated. PURPOSE: The purpose of this study was to evaluate and compare the shade-matching ability of dental technician students and graduate dentists using the Vita 3D-Master shade guide. MATERIAL AND METHODS: Twenty-nine dental technician students (DTS group) and 30 graduate dentists (GD group) participated in this study. The Toothguide Training Box (TTB) was used to train the participants and test their shade-matching abilities. Shade-matching ability was evaluated with 3 exercises and a final test, all of which are components of the TTB. The number of mistakes for each participant for value (L), chroma (c), and hue (h) were recorded during the exercises and the final test, and the mistake ratios were calculated. Color difference (DeltaE) values for each shade were calculated from the L*, a*, and b* values of the Vita 3D-Master shade guide for each participant in both groups. The Mann-Whitney U test was used to determine statistically significant differences between the L, c, and h mistake ratios of the 2 groups, and the Student t test was used to determine statistically significant differences between the final test scores and the DeltaE values of the groups (alpha=.05). RESULTS: The mistake ratio for L in the GD group was significantly higher than that of the DTS group (P<.05), whereas the mistake ratio for h in the DTS group was higher (P<.001). No significant differences were observed between the groups regarding the mistake ratios for c (P>.05). With regard to the final test scores and the DeltaE values, no significant differences were found between the groups (P<.001), and the DTS group received higher scores than the GD group (912 and 851). The mean DeltaE values for the DTS and GD groups were 1.72 and 2.92. CONCLUSIONS: DTSs made more mistakes in the h parameter than GDs, and GDs made more mistakes in the L parameter than DTSs. With regard to the final test scores and the DeltaE values, DTSs were more successful in shade matching than GDs. PMID- 25134994 TI - Evaluation of an optimized shade guide made from porcelain powder mixtures. AB - STATEMENT OF PROBLEM: Color errors associated with current shade guides and problems with color selection and duplication are still challenging for restorative dentists. PURPOSE: The purpose of this study was to evaluate an optimized shade guide for visual shade duplication. MATERIAL AND METHODS: Color distributions (L*, a*, and b*) of the maxillary left central incisors of 236 participants, whose ages ranged from 20 to 60, were measured with a spectrophotometer. Based on this color map, an optimized shade guide was designed with 14 shade tabs evenly distributed within the given color range of the natural incisors. The shade tabs were fabricated with porcelain powder mixtures and conventional laboratory procedures. A comparison of shade duplication by using the optimized and Vitapan Classical shade guides was conducted. Thirty Chinese participants were involved, and the colors of the left maxillary incisors were selected by using 2 shade guides. Metal ceramic crowns were fabricated according to the results of the shade selection. The colors of the shade tabs, natural teeth, and the ceramic crowns were measured with a spectrophotometer. The color differences among the natural teeth, the shade tabs, and the corresponding metal ceramic crowns were calculated and analyzed (alpha=.017). RESULTS: Significant differences were found in both phases of shade determination and shade duplication (P<.017). The total number of color errors with the optimized shade guide was 3.5, which was significantly less than that of Vitapan, 5.1 (P<.001). CONCLUSIONS: The optimized shade guide system improved performance not only in the color selection phase but also in the color of the fabricated crowns. PMID- 25134995 TI - Scanning accuracy and precision in 4 intraoral scanners: an in vitro comparison based on 3-dimensional analysis. AB - STATEMENT OF PROBLEM: Intraoral scanners may use proprietary acquisition and manufacturing processes. However, limited information is available regarding their accuracy, their precision, and the influence that refraction or coating may have on their output. PURPOSE: The purpose of the study was to evaluate the scanning accuracy and precision of 4 intraoral scanners and to assess the influence of different test materials and coating thicknesses. MATERIAL AND METHODS: Models were fabricated in 3 materials (polymethyl methacrylate [Telio CAD], titanium, and zirconia) and reference scanned with an industrial optical scanner. The models were scanned with intraoral scanners (3M Lava COS, Cerec AC/Bluecam, E4D, and iTero). A thick layer of coating was applied and scanned (3M Lava COS). Further evaluation on a gypsum cast was undertaken for the E4D system. Data were evaluated by using 3-dimensional analysis with "3D compare" software commands (3D compare analysis) regarding standard, mean, and maximum deviations, with subsequent statistical analysis. RESULTS: The 3M Lava COS, Cerec AC/Bluecam, and iTero generally displayed similar results regarding deviations. Maximum deviations, however, increased by several factors for the noncoating scanners (iTero and E4D). Statistical significance was found regarding material properties for noncoating scanners (P<.05). iTero displayed consistent material-specific, localized errors on the translucent material (Telio CAD). E4D showed the largest deviations. Scans of the gypsum cast displayed specific localized areas with greater deviations. Excessive coating was nonsignificant. CONCLUSIONS: Significant differences were found between the coating and noncoating scanners, and specific scanning errors for the system with parallel confocal microscopy were found for certain model materials. Specific areas of sizable deviations for the system with laser triangulation technology can be explained by the scanner design and noncoating technology. Excessive coating had no negative effect. PMID- 25134996 TI - Effect of gypsum separating media on the appearance of stone cast surfaces. AB - STATEMENT OF PROBLEM: Several well-known parameters influence the appearance of the denture base surface, including proper isolation of the dental stone. There is lack of data describing the influence of this parameter on the appearance of the denture base surface. PURPOSE: The purpose of this study was to evaluate the effectiveness of 2 dental stone separating media on the surface of the denture base. MATERIAL AND METHODS: A conventional flasking technique for fabricating a denture base was used. Twenty casts were poured with Type III yellow dental stone to produce 20 identical denture bases. Each cast was sectioned into halves. One half of the cast was treated with Al-Cote (control group) and the other half with Iso-K separating material. Once the denture base was finished, a single examiner, blinded to the experiment, visually compared the 2 surfaces of each cast (right and left part of the cast) under natural light to determine which surface was glossier. The McNemar test (.05 significance level) was used to compare the discordant pairs (20 discordant pairs). RESULTS: Two pairs (10%) were glossier than the Iso-K treatment, and 18 pairs (90%) within the Iso-K treatment were glossier than the treatment with Al-Cote. A statistically significant difference was found between the 2 treatments (P<.001). The odds ratio was 9.00, with a 95% confidence interval of 2.155 to 79.981. CONCLUSIONS: When used according to the manufacturer's instructions, denture surfaces treated with Iso-K appeared glossier than when treated with Al-Cote separating material. PMID- 25134997 TI - A technique to evaluate custom tray border extensions before peripheral molding. PMID- 25134998 TI - Methylated ZNF582 gene as a marker for triage of women with Pap smear reporting low-grade squamous intraepithelial lesions - a Taiwanese Gynecologic Oncology Group (TGOG) study. AB - OBJECTIVE: Our previous work revealed that host genes ZNF582, PTPRR, PAX1, and SOX1 are highly methylated in cervical intraepithelial neoplasias grade 3 or worse (CIN3(+)). In this study, we used a standardized testing assay to evaluate the clinical efficacy of these biomarkers in the triage of cytological diagnoses of low-grade squamous intraepithelial lesions (LSILs), and compared the performance with human papillomavirus (HPV) testing. METHODS: This 2-year multicenter prospective study examined a population of 230 women from 12 medical centers who were diagnosed with LSILs on cervical cytology. Cervical scrapings were obtained prior to a colposcopy-directed biopsy for quantitative methylation analysis of ZNF582, PTPRR, PAX1, and SOX1, and HPV testing. Using logistic regression and receiver operating characteristic curve analyses, the abilities of methylated genes and HPV to predict CIN3(+) were assessed. RESULTS: Fifteen (6.5%) of the 230 women with a cytological diagnosis of LSIL were confirmed to have CIN3(+) after a colposcopy-directed biopsy. Among the 4 methylated genes, ZNF582 was found to be the best biomarker for detecting CIN3(+). The sensitivities for methylated ZNF582 and HPV testing were 73% and 80%, and the specificities were 71% and 28%, respectively. The odds ratio for predicting CIN3(+) using methylated ZNF582 was 6.8 (95% confidence interval (CI) 2.1-22.1), which was much better than HPV testing (OR=1.6, 95% CI 0.4-5.8). CONCLUSION: This is the first study to show that ZNF582 methylation analysis of cervical swabs may be a promising choice in the positive triage of cytological diagnoses of LSILs. PMID- 25135000 TI - Role of toll-like receptors in cervical, endometrial and ovarian cancers: a review. AB - OBJECTIVE: The Toll-like receptors (TLRs) have been implicated in inflammation, innate immunity and cancer. The goal of this paper is to review the available published research about Toll-like receptors and their roles in gynecologic malignancies. METHODS: A Medline search was conducted and published articles from the late 1990s to the present (2014) were reviewed using search phrases, Toll like receptors and cervical, endometrial and ovarian cancers. RESULTS: TLR4 and TLR5 are commonly absent in normal cervix, however TLR5 expression is strong in high grade cervical dysplasia as well as invasive cancer. The expression of TLR3 and TLR4 is low in endometrial cancer. TLR2, TLR3, TLR4 and TLR5 are highly expressed in normal and neoplastic ovarian epithelium. TLR3 has been shown to have a dual function: it can contribute to tumor elimination by upregulation of interferons alpha and beta (INF) and natural killer cell (NK) activation or it can indirectly contribute to tumor progression. CONCLUSIONS: Inflammation is an essential element in tumorigenesis. Toll-like receptors can trigger an inflammatory response and cell survival in the tumor micro-environment. TLRs are critical immunomodulators that may play an important role in the development of gynecologic cancers. Currently TLR agonists are being investigated for a potential role as an adjuvant in the treatment of gynecologic malignancies. PMID- 25135001 TI - Needs assessment of palliative care education in gynecologic oncology fellowship: we're not teaching what we think is most important. AB - OBJECTIVES: We sought to characterize gynecologic oncology fellowship directors' perspectives on (1) inclusion of palliative care (PC) topics in current fellowship curricula, (2) relative importance of PC topics and (3) interest in new PC curricular materials. METHODS: An electronic survey was distributed to fellowship directors, assessing current teaching of 16 PC topics meeting ABOG/ASCO objectives, relative importance of PC topics and interest in new PC curricular materials. Descriptive and correlative statistics were used. RESULTS: Response rate was 63% (29/46). 100% of programs had coverage of some PC topic in didactics in the past year and 48% (14/29) have either a required or elective PC rotation. Only 14% (4/29) have a written PC curriculum. Rates of explicit teaching of PC topics ranged from 36% (fatigue) to 93% (nausea). Four of the top five most important PC topics for fellowship education were communication topics. There was no correlation between topics most frequently taught and those considered most important (rs=0.11, p=0.69). All fellowship directors would consider using new PC curricular materials. Educational modalities of greatest interest include example teaching cases and PowerPoint slides. CONCLUSIONS: Gynecologic oncology fellowship directors prioritize communication topics as the most important PC topics for fellows to learn. There is no correlation between which PC topics are currently being taught and which are considered most important. Interest in new PC curricular materials is high, representing an opportunity for curricular development and dissemination. Future efforts should address identification of optimal methods for teaching communication to gynecologic oncology fellows. PMID- 25134999 TI - Oxysterols synergize with statins by inhibiting SREBP-2 in ovarian cancer cells. AB - OBJECTIVE: Determine mechanisms responsible for enhanced statin efficacy in a novel statin combination we name STOX (STatin-OXysterol). METHODS: Ovarian cancer cell lines were treated with combinations of statins and oxysterols. Cell viability was determined by a modified MTT assay. Apoptosis was evaluated by immunoblotting of PARP and DAPI-mediated visualization of apoptotic nuclei. STOX effects on the expression of genes of the mevalonate pathway were assessed by real-time qPCR and immunoblotting. siRNA-mediated gene silencing was used to test the involvement of oxysterol-mediated repression of SREBP-2 in STOX synergy. The impact of statin-mediated inhibition of protein prenylation and on cholesterol homeostasis was evaluated. RESULTS: Oxysterols dramatically enhance cytotoxicity of statins in ovarian cancer cells through increased apoptosis. Decreased expression of SREBP-2 down-regulates the mevalonate pathway and prevents the active statin-induced sterol feedback, enhancing statin toxicity. Comparison of two ovarian cancer cell lines reveals two distinct mechanisms of statin induced toxicity, namely, dependence on protein geranylgeranylation and/or perturbation of cellular cholesterol levels. CONCLUSIONS: We provide evidence of statins' mechanisms of cytotoxicity in different ovarian cancer cells and discovered a new approach to significantly enhance the anti-tumor activity of statins. These observations provide a potential new path to improve statins as a treatment against ovarian cancer with obtainable dosages. PMID- 25135002 TI - Factors affecting diagnosis and management of hypertension in Mazowe District of Mashonaland Central Province in Zimbabwe: 2012. AB - BACKGROUND: From 2005 to 2011 Mazowe District recorded a gradual decline in prevalence of hypertension in the face of rising incidence of complications like stroke. This raised questions on whether diagnosis and management of hypertensive patients is being done properly. METHODS: We conducted an analytic cross sectional study at three hospitals in Mazowe District where we randomly selected 201 of 222 patients from out patients departments and interviewed a convenience sample of 23 healthcare workers. Structured interviewer administered questionnaires were used to collect data on demographic characteristics and knowledge from patients, as well as knowledge and practices from health workers. Physical measurements were done on all patients. Frequencies; proportions, odds ratios, Chi square test and stratified & logistic regression analysis were done using Epi info version 3.5.4 while graphs were generated using Microsoft excel(r). Calculations were done at 95% confidence interval. RESULTS: Prevalence, awareness, control, compliance, and complication rate of hypertension were: 69.7%, 56.2%, 22.0%, 59.8% and 20.7% respectively. Independent risk factors for hypertension were age (POR 3.09; 95% CI: 1.27-7.5), obesity (POR 4.37; 95% CI: 1.83-10.4), and previous high blood pressure reading (POR 19.86; 95% CI: 8.61 45.8). Complications included cardiac failure (8.6%), visual defects (4.3%) and stroke (3.6%). Co-morbid human immunodeficiency virus (10.7%) and diabetes mellitus (12.1%) were identified among respondents. Knowledge was poor in 47.7% of health workers. CONCLUSIONS: Risk factors found in this study are consistent with other studies. Health service factors are the main reasons for poor diagnosis and management of hypertension. Health workers need training on diagnosis and management of hypertension. Guidelines, digital sphygmomanometers and adequate drug supply are needed. District has since purchased digital BP machines and requested assistance with training on clinical features of hypertension, use of digital machines, and how to properly measure BP. A policy document on non-communicable diseases including hypertension was subsequently developed by the Ministry of Health and Child Care and currently awaiting endorsement by parliament. PMID- 25135003 TI - Facilitation of corticospinal excitability by virtual reality exercise following anodal transcranial direct current stimulation in healthy volunteers and subacute stroke subjects. AB - BACKGROUND: There is growing evidence that the combination of non-invasive brain stimulation and motor skill training is an effective new treatment option in neurorehabilitation. We investigated the beneficial effects of the application of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) motor training. METHODS: In total, 15 healthy, right-handed volunteers and 15 patients with stroke in the subacute stage participated. Four different conditions (A: active wrist exercise, B: VR wrist exercise, C: VR wrist exercise following anodal tDCS (1 mV, 20 min) on the left (healthy volunteer) or affected (stroke patient) primary motor cortex, and D: anodal tDCS without exercise) were provided in random order on separate days. We compared during and post-exercise corticospinal excitability under different conditions in healthy volunteers (A, B, C, D) and stroke patients (B, C, D) by measuring the changes in amplitudes of motor evoked potentials in the extensor carpi radialis muscle, elicited with single-pulse transcranial magnetic stimulation. For statistical analyses, a linear mixed model for a repeated-measures covariance pattern model with unstructured covariance within groups (healthy or stroke groups) was used. RESULTS: The VR wrist exercise (B) facilitated post-exercise corticospinal excitability more than the active wrist exercise (A) or anodal tDCS without exercise (D) in healthy volunteers. Moreover, the post-exercise corticospinal facilitation after tDCS and VR exercise (C) was greater and was sustained for 20 min after exercise versus the other conditions in healthy volunteers (A, B, D) and in subacute stroke patients (B, D). CONCLUSIONS: The combined effect of VR motor training following tDCS was synergistic and short-term corticospinal facilitation was superior to the application of VR training, active motor training, or tDCS without exercise condition. These results support the concept of combining brain stimulation with VR motor training to promote recovery after a stroke. PMID- 25135004 TI - Steady-state sulfur critical loads and exceedances for protection of aquatic ecosystems in the U.S. Southern Appalachian Mountains. AB - Atmospherically deposited sulfur (S) causes stream water acidification throughout the eastern U.S. Southern Appalachian Mountain (SAM) region. Acidification has been linked with reduced fitness and richness of aquatic species and changes to benthic communities. Maintaining acid-base chemistry that supports native biota depends largely on balancing acidic deposition with the natural resupply of base cations. Stream water acid neutralizing capacity (ANC) is maintained by base cations that mostly originate from weathering of surrounding lithologies. When ambient atmospheric S deposition exceeds the critical load (CL) an ecosystem can tolerate, stream water chemistry may become lethal to biota. This work links statistical predictions of ANC and base cation weathering for streams and watersheds of the SAM region with a steady-state model to estimate CLs and exceedances. Results showed that 20.1% of the total length of study region streams displayed ANC <100 MUeq?L(-1), a level at which effects to biota may be anticipated; most were 4th or lower order streams. Nearly one-third of the stream length within the study region exhibited CLs of S deposition <50 meq?m(-2)?yr( 1), which is less than the regional average S deposition of 60 meq?m(-2)?yr(-1). Owing to their geologic substrates, relatively high elevation, and cool and moist forested conditions, the percentage of stream length in exceedance was highest for mountain wilderness areas and in national parks, and lowest for privately owned valley bottom land. Exceedance results were summarized by 12-digit hydrologic unit code (subwatershed) for use in developing management goals and policy objectives, and for long-term monitoring. PMID- 25135005 TI - Consumer willingness to invest money and time for benefits of lifestyle behaviour change: an application of the contingent valuation method. AB - OBJECTIVE: To use contingent valuation (CV) to derive individual consumer values for both health and broader benefits of a public-health intervention directed at lifestyle behaviour change (LBC) and to examine the feasibility and validity of the method. METHOD: Participants of a lifestyle intervention trial (n = 515) were invited to complete an online CV survey. Respondents (n = 312) expressed willingness to invest money and time for changes in life expectancy, health related quality of life (HRQOL) and broader quality of life aspects. Internal validity was tested for by exploring associations between explanatory variables (i.e. income, paid work, experience and risk factors for cardiovascular diseases) and willingness to invest, and by examining ordering effects and respondents' sensitivity to the scope of the benefits. RESULTS: The majority of respondents (94.3%) attached value to benefits of LBC, and 87.4% were willing to invest both money and time. Respondents were willing to invest more for improvements in HRQOL (?42/month; 3 h/week) and broader quality of life aspects (?40/month; 2.6 h/week) than for improvements in life expectancy (?24/month; 2 h/week). Protest answers were limited (3%) and findings regarding internal validity were mixed. CONCLUSION: The importance of broader quality of life outcomes to consumers suggests that these outcomes are relevant to be considered in the decision making. Our research showed that CV is a feasible method to value both health and broader outcomes of LBC, but generalizability to other areas of public health still needs to be examined. Mixed evidence regarding internal validity pleads for caution to use CV as only the base for decision making. PMID- 25135006 TI - What level of bowel prep quality requires early repeat colonoscopy: systematic review and meta-analysis of the impact of preparation quality on adenoma detection rate. AB - OBJECTIVES: Current guidelines recommend early repeat colonoscopy when bowel preparation quality is inadequate, defined as inability to detect polyps >5 mm, but no data link specific bowel preparation categories or scores to this definition. Nevertheless, most physicians use a shortened screening/surveillance interval in patients with intermediate-quality preparation. We determined whether different levels of bowel preparation quality are associated with differences in adenoma detection rates (ADRs: proportion of colonoscopies with >=1 adenoma) to help guide decisions regarding early repeat colonoscopy-with primary focus on intermediate-quality preparation. METHODS: MEDLINE and Embase were searched for studies with adenoma or polyp detection rate stratified by bowel preparation quality. Preparation quality definitions were standardized on the basis of Aronchick definitions (excellent/good/fair/poor/insufficient), and primary analyses of ADR trichotomized bowel preparation quality: high quality (excellent/good), intermediate quality (fair), and low quality (poor/insufficient). Dichotomized analyses of adequate (excellent/good/fair) vs. inadequate (poor/insufficient) were also performed. RESULTS: Eleven studies met the inclusion criteria. The primary analysis, ADR with intermediate- vs. high quality preparation, showed an odds ratio (OR) of 0.94 (0.80-1.10) and absolute risk difference of -1% (-3%, 2%). ADRs were significantly higher with both intermediate-quality and high-quality preparation vs. low-quality preparation: OR=1.39 (1.08-1.79) and 1.41 (1.21-1.64), with absolute risk increases of 5% for both. ADR and advanced ADR were significantly higher with adequate vs. inadequate preparation: OR=1.30 (1.19-1.42) and 1.30 (1.02-1.67). Studies did not report other relevant outcomes such as total adenomas per colonoscopy. CONCLUSIONS: ADR is not significantly different with intermediate-quality vs. high-quality bowel preparation. Our results confirm the need for early repeat colonoscopy with low quality bowel preparation, but suggest that patients with intermediate/fair preparation quality may be followed up at standard guideline-recommended surveillance intervals without significantly affecting quality as measured by ADR. PMID- 25135007 TI - Miralax with gatorade for bowel preparation: a meta-analysis of randomized controlled trials. AB - OBJECTIVES: Polyethylene glycol (PEG) is a very popular bowel preparation for colonoscopy. However, its large volume may reduce patient compliance, resulting in suboptimal preparation. Recently, a combination of Miralax and Gatorade has been studied in various randomized controlled trials (RCTs) as a lower volume and more palatable bowel preparation. However, results have varied. Therefore, we conducted a meta-analysis assessing the use of Miralax-Gatorade (M-G) vs. PEG for bowel preparation before colonoscopy. METHODS: Multiple databases were searched (January 2014). RCTs on adults comparing M-G (238-255 g in 1.9 l that is 64 fl oz) vs. PEG (3.8-4 l) for bowel preparation before colonoscopy were included. The effects were analyzed by calculating pooled estimates of quality of bowel preparation (satisfactory, unsatisfactory, excellent), patient tolerance (nausea, cramping, bloating), and polyp detection by using odds ratio (OR) with fixed- and random-effects models. RESULTS: Five studies met inclusion criteria (N=1,418), with mean age ranging from 53.8 to 61.3 years. M-G demonstrated statistically significantly fewer satisfactory bowel preparations as compared with PEG (OR 0.65; 95% confidence interval (CI): 0.43-0.98, P=0.04) but more willingness to repeat preparation (OR 7.32; 95% CI: 4.88-10.98, P<0.01). Furthermore, no statistically significant differences in polyp detection (P=0.65) or side effects were apparent between the two preparations for nausea (P=0.71), cramping (P=0.84), or bloating (P=0.50). Subgroup analysis revealed similar results for split-dose M-G vs. split-dose PEG. CONCLUSIONS: M-G for bowel preparation before colonoscopy was inferior to PEG in bowel preparation quality while demonstrating no significant improvements in adverse effects or polyp detection. Therefore, PEG appears superior to M-G for bowel preparation before colonoscopy. PMID- 25135008 TI - ACG clinical guideline: the diagnosis and management of focal liver lesions. AB - Focal liver lesions (FLL) have been a common reason for consultation faced by gastroenterologists and hepatologists. The increasing and widespread use of imaging studies has led to an increase in detection of incidental FLL. It is important to consider not only malignant liver lesions, but also benign solid and cystic liver lesions such as hemangioma, focal nodular hyperplasia, hepatocellular adenoma, and hepatic cysts, in the differential diagnosis. In this ACG practice guideline, the authors provide an evidence-based approach to the diagnosis and management of FLL. PMID- 25135009 TI - Characterization of type III TGF-beta receptor expression in invasive breast carcinomas: a potential new marker and target for triple negative breast cancer. AB - Invasive breast carcinomas are heterogeneous and exhibit distinct molecular features and biological behavior. Understanding the underlying molecular events that promote breast cancer progression is necessary to improve treatment and prognostication. TGF-beta receptor III (TBR3) is a member of the TGF-beta signaling pathway, with functions in cell proliferation and migration in malignancies, including breast cancer. Recent studies propose that TBR3 may function as a tumor suppressor and that its loss may correlate with disease progression. However, there are limited data on the expression of TBR3 in breast cancer in relationship to tumor type, hormonal receptor status and HER-2/neu, and patient outcome. In this study, we investigated the expression of TBR3 in a cohort of 205 primary invasive breast carcinomas in tissue microarrays (TMAs), with comprehensive clinical, pathological and follow- up information. Sections were stained for TBR3 and evaluated for intensity of reactivity based on a 4 tiered scoring system (1 to 4; TBR3 low = scores 1-2; TBR3 high = scores 3-4). Of the 205 invasive carcinomas, 123 were luminal type (95 type A, 28 type B), 8 were HER-2 type, and 62 were triple negative (TN). TBR3 was high in 112 (55 %) and low in 93 (45 %) cases. Low TBR3 was associated with higher histological grade and worse disease free and overall survival, all features of biologically aggressive breast carcinomas. TBR3 was significantly associated with the subtype of breast cancer, as low TBR3 was detected in 95 % of TN compared to 22 % of luminal tumors (p < 0.0001). We discovered a significant association between low TBR3 protein expression, TN breast cancer phenotype, and disease progression. These data suggest that TBR3 loss might be linked to the development of TN breast cancers and pave the way to investigating whether restoring TBR3 function may be a therapeutic strategy against TN breast carcinomas. PMID- 25135010 TI - Impact of antigenic diversity on laboratory diagnosis of Avian bornavirus infections in birds. AB - Avian bornaviruses (ABVs) are a group of genetically diverse viruses within the Bornaviridae family that can infect numerous avian species and represent the causative agents of proventricular dilatation disease, an often fatal disease that is widely distributed in captive populations of parrots and related species. The current study was designed to assess the antigenic variability of the family Bornaviridae and to determine its impact on ABV diagnosis by employing fluorescent antibody assays. It was shown that polyclonal rabbit sera directed against recombinant bornavirus nucleoprotein, X protein, phosphoprotein, and matrix protein provided sufficient cross-reactivity for the detection of viral antigen from a broad range of bornavirus genotypes grown in cell culture. In contrast, a rabbit anti-glycoprotein serum and 2 monoclonal antibodies directed against nucleoprotein and phosphoprotein proteins reacted more specifically. Antibodies were readily detected in sera from avian patients infected with known ABV genotypes if cells persistently infected with a variety of different bornavirus genotypes were used for analysis. For all sera, calculated antibody titers were highest when the homologous or a closely related target virus was used for the assay. Cross-reactivity with more distantly related genotypes of other phylogenetic groups was usually reduced, resulting in titer reduction of up to 3 log units. The presented results contribute to a better understanding of the antigenic diversity of family Bornaviridae and further emphasize the importance of choosing appropriate diagnostic tools for sensitive detection of ABV infections. PMID- 25135011 TI - Foot-and-mouth disease in Asiatic black bears (Ursus thibetanus). AB - Foot-and-mouth disease (FMD) is a highly contagious, debilitating, and globally significant viral disease typically affecting cloven-hoofed hosts. The diagnosis of FMD in bears in Vietnam is described. The current study describes a confirmed case of FMD in a bear species, and the clinical signs compatible with FMD in a Malayan sun bear. Thirteen Asiatic black bears (Ursus thibetanus) and 1 Malayan sun bear (Helarctos malayanus) were apparently affected. In August 2011, an adult bear became lethargic, and developed footpad vesicles. Over 15 days, 14 out of 17 bears developed similar signs; the remaining 3 co-housed bears and another 57 resident bears did not. All affected bears developed vesicles on all footpads, and most were lethargic for 24-48 hr. Nasal and oral lesions were noted in 6 and 3 cases, respectively. Within 1 month, all looked normal. Foot-and-mouth disease virus (FMDV) was detected by reverse transcription polymerase chain reaction, classified as serotype O, and isolated by virus isolation techniques. Phylogenetic analysis demonstrated clustering of 3 bear isolates, in a branch distinct from other FMDV type O isolates. The outbreak likely occurred due to indirect contact with livestock, and was facilitated by the high density of captive bears. It showed that Asiatic black bears are capable of contracting FMDV and developing clinical disease, and that the virus spreads easily between bears in close contact. PMID- 25135012 TI - Adoption and compliance in second-hand smoking bans: a global econometric analysis. AB - OBJECTIVES: We examine the determinants governing both countries' enactment of smoking bans in public places and their ability to successfully put these bans into effect. METHODS: Using a large sample (N = 99-184) of low-, middle- and high income countries, econometric techniques are used to estimate the influence of several variables on cross-national variations in the adoption and compliance of second-hand smoke laws (2010). RESULTS: We find similarities in the determinants of adoption and compliance. Yet more notable are the differences, with several political economy factors which have a statistically significant influence on countries' level of compliance with existing smoke-free laws in public places found not to consistently influence their propensity to adopt bans in the first place. Possible explanations for this discrepancy are that governments are motivated to adopt smoking bans for reasons other than protecting the health of their citizens and that the real costs of smoking bans are predominantly borne at the compliance stage. CONCLUSIONS: More effort needs to be made to ensure that governments realize their existing policy commitments through effective enforcement of bans. PMID- 25135013 TI - Electronic cigarettes: proceed with great caution. PMID- 25135014 TI - Analysis of cardiac and pulmonary injuries resulting from an experimental penetrating thoracic injury. AB - BACKGROUND: This study was planned to analyze the internal and external anatomical findings of cardiac injuries and the presence of accompanying pulmonary injuries in intentionally inflicted thoracic injuries to swine models. METHODS: We inflicted a penetrating heart injury in six suis domesticus female swine models. Two cardiac injuries, one on the left paratracheal of fourth intercostal space (ICS) and the other on the right side were inflicted on each model by the same researcher using a 20-cm long scalpel. All animals were then sacrificed for morphological evaluation. RESULTS: After strikes to the left fourth ICS, external evaluation showed that 50% of the subjects suffered a single laceration and that 33% suffered multiple lacerations. Internal evaluation showed additional intracardiac injuries in all five subjects. However, the subject that suffered a single laceration on the outer surface of the heart had multiple internal injuries while another subject that had multiple outer lacerations had only one intracardiac injury. Only three subjects suffered cardiac injuries and only two out of those three with pulmonary injuries after right fourth intercostal intrusions. CONCLUSION: This experiment has shown that external evaluation of the heart tissue may not alone be sufficient to determine the extent of cardiac injuries and accompanying pulmonary injuries caused by penetrating thoracic injuries. PMID- 25135015 TI - The effects of oral antibiotics on infection prophylaxis in traumatic wounds. AB - BACKGROUND: The objective of this study is to examine the effectiveness of oral antibiotics in the prevention of infection development in traumatic wounds. METHODS: Forty Wistar albino rats were divided into five groups of eight animals. After the crushed wound model was made on the back of the rats, wounds were closed with a simple suture and Staphylococcus aureus ATCC 29213 strain was used to create infection. All rats apart from the controls were given oral gavage with antibiotics, including cephalexin, amoxicillin-clavulanate, clarithromycin (CAM), or levofloxacin for 5 days. Wounds were evaluated qualitatively and quantitatively on 5th day approximately 18 h after the last treatment. RESULTS: In the quantitative evaluation, no infection was observed in the treatment groups with amoxicillin-clavulanate, CAM, cephalexin, or levofloxacin. There was no significant difference on the numbers of bacteria found in the wounds among the groups. In terms of quantitative inflammation findings, no hyperemia or pus was detected in the groups that were given medication. Furthermore, no statistically significant difference was found among the groups in terms of induration. CONCLUSION: Oral prophylactic antibiotics have been found to be effective in the prevention of wound infection in the traumatic crushed wound model infected with S. aureus in rats. PMID- 25135016 TI - Correlation between arterial blood gas analysis and outcome in patients with severe head trauma. AB - BACKGROUND: Traumatic brain injury is one of the major concerns of global public health, because it is the main cause of morbidity and mortality between young people. This study aimed to investigate the possible association between the parameters of arterial blood gas (ABG) and outcome of patients with severe head trauma. METHODS: In this prospective study, 70 patients with severe head trauma were studied in Urmia Imam Khomeini hospital during 18-month period of time. The parameters of ABG were documented within the 1st hour of admission, and their correlation was evaluated with Glasgow coma scale (GCS) and Glasgow outcome score (GOS). These parameters also were compared between expired and discharged patients. RESULTS: Seventy patients with severe head trauma including 60 males (85.7%) and 10 females (14.3%) with a mean age of 34.34+/-14.82 (range: 18-76) years were studied. The mortality rate during hospitalization was 38.6% (n=27). There was no significant correlation between the parameters of ABG and GCS score and GOS scores. Furthermore, there was no significant difference between the survivors and non-survivors in terms of the mean value of ABG parameters (p>0.05). CONCLUSION: ABG at the time of admission is not a significant predictor of outcome in patients with severe head trauma. PMID- 25135017 TI - Value of the Glasgow coma scale, age, and arterial blood pressure score for predicting the mortality of major trauma patients presenting to the emergency department. AB - BACKGROUND: The purpose of this study is to detect the mortality predictive power of new Glasgow coma scale, age, and arterial pressure (GAP) scoring system in major trauma patients admitted to the emergency department (ED). METHODS: A total of 100 major trauma patients admitted to Uludag University Faculty of Medicine ED who were 18 years of age or more were included in the study. In this prospective study, revised trauma score (RTS), injury severity score (ISS), trauma-related ISS (TRISS), Mechanism, GAP (MGAP) and GAP scores of the patients were calculated. RESULTS: A significant positive correlation was established between ISS, TRISS, MGAP, and GAP in predicting in-hospital mortality (p<0.0001). Short term (24 hours) and long-term (4-week) mortality prediction rates and area under the curve in receiver operating characteristics analysis were 0.727-0.680 for RTS, 0.863-0.816 for ISS, 0.945-0,911 for TRISS, 0.970-0.938 for MGAP, and 0.910 0.904 for GAP. All calculated trauma scoring systems revealed a significant mortality prediction power (p<0.001). GAP score was found statistically and significantly selective and sensitive in predicting both in-ED and in-hospital mortality (p=0.0001). CONCLUSION: In major trauma patients, GAP score is an easily calculable system both in the field and at the time of admission in the EDs by providing emergency physicians with future decision-making schemes by means of mortality prediction of the patients. PMID- 25135018 TI - Impact of smoking on trauma patients. AB - BACKGROUND: The harmful effects of smoking have been well-documented in the medical literature for decades. To further the support of smoking cessation, we investigate the effect of smoking on a less studied population, the trauma patient. METHODS: All trauma patients admitted to the surgical intensive care unit at the LAC + University of Southern California medical center between January 2007 and December 2011 were included. Patients were stratified into two groups - current smokers and non-smokers. Demographics, admission vitals, comorbidities, operative interventions, injury severity indices, and acute physiology and chronic health evaluation (APACHE) II scores were documented. Uni- and multi-variate modeling was performed. Outcomes studied were mortality, duration of mechanical ventilation, and length of hospitalization. RESULTS: A total of 1754 patients were available for analysis, 118 (6.7%) patients were current smokers. The mean age was 41.4+/-20.4, 81.0% male and 73.5% suffered blunt trauma. Smokers had a higher incidence of congestive heart failure (4.2% vs. 0.9%, p=0.007) and alcoholism (20.3% vs. 5.9%, p<0.001), but had a significantly lower APACHE II score. After multivariate regression analysis, there was no significant mortality difference. Patients who smoked spent more days mechanically ventilated (beta coefficient: 4.96 [1.37, 8.55, p=0.007]). CONCLUSION: Smoking is associated with worse outcome in the critically ill trauma patient. On an average, smokers spent 5 days longer requiring mechanical ventilation than non-smokers. PMID- 25135019 TI - Etiology and prognosis of penetrating eye injuries in geriatric patients in the Southeastern region of Anatolia Turkey. AB - BACKGROUND: The purpose of this study was to evaluate the etiologic and prognostic factors of open eye injuries in geriatric patients in the Southeastern region of Anatolia. METHODS: Forty-five geriatric patients who underwent surgery for an open eye injury in our clinic between the years of 2008 and 2012 were evaluated retrospectively. Age, gender, cause and the mechanism of the trauma, visual acuity (VA), and the time between the trauma and the surgery were obtained from files and evaluated. RESULTS: The mean age of the patients was 70.4+/-8.2 (65-90) years. Thirty-four of the cases were male and 11 were female. The most frequent mechanism of trauma was a wood strike, while the second most common one was injury with a knife. Corneoscleral penetration was the most frequently observed trauma. The mean VA of the patients was 2.26+/-0.65 at admission, and was 1.53+/-0.99 logarithm of the minimum angle of resolution at the final evaluation. The most frequent complications of trauma were iris prolapse and hyphema. There was a significant correlation between the first and final VA. CONCLUSION: Penetrating ocular injuries are seen less frequently among geriatric patients, and their prognosis may be worse due to less-efficient wound site healing and differences in scleral rigidity. The most important factor affecting the final VA measurement was the VA of the patient at admission. PMID- 25135020 TI - Comparison of trauma scores for predicting mortality and morbidity on trauma patients. AB - BACKGROUND: In this study, we compared the anatomical, and physiological scoring systems trauma revised injury severity score (TRISS), revised trauma score (RTS), injury severity score (ISS), new injury severity score (NISS) to each other, to find out the most accurate and reliable trauma score for the risk classification of morbidity and mortality among the trauma patients. METHODS: This is a cross sectional study, which included 633 patients who admitted to our University Hospital Emergency Department during an 8-month period due to trauma. All blunt and penetrating traumas (traffic accident, assault, etc.) patients above 16 years were included. RESULTS: Arrival time trauma scores (ISS, NISS, RTS, and TRISS) of the patients was calculated. Mean trauma score for the mortality prediction was calculated, and the p value was equal for all (p=0.001). Trauma scores were also analyzed for the hospitalization time in intensive care unit (ICU). While NISS, RTS, and TRISS values were significant (p=0.048, p=0.048, and p=0.017, respectively), ISS value was not significant (p=0.257) for predicting the ICU hospitalization time. Only TRISS was a good predictor for the mechanically ventilation time in ICU patients (p=0.01). CONCLUSION: In conclusion, we determined that the anatomical trauma scores (NISS, ISS) predicted the hospitalization and ICU necessities better, whereas TRISS, an anatomo physiological trauma score, defined the ICU hospitalization and mechanically ventilation time better. PMID- 25135021 TI - Experience of 80 cases with Fournier's gangrene and "trauma" as a trigger factor in the etiopathogenesis. AB - BACKGROUND: The purpose of the present study was to retrospectively analyze the patients' data presented with Fournier's gangrene (FG), to compare obtained data with the literature and to investigate the role of "trauma" in the etiopathogenesis. METHODS: A retrospective study was conducted on 126 patients with FG that consulted to our department. RESULTS: There were 76 male and four female patients. The mean age of the patients was 53.5+/-13.6 years. The most common presentation of patients was swelling (n=74). The scrotum has been shown to be the most commonly affected area in the patients (n=75). Diabetes mellitus was the leading predisposing factor and trauma was the leading responsible cause for FG. Escherichia coli was the most frequently identified microorganism (n=43, 53.75%). Primary closure was the most common technique used for all patients. Three patients exhibited a mortal course due to sepsis and multi-organ failure. CONCLUSION: FG still has a high mortality rate. Rapid and correct diagnosis of the disease can avoid inappropriate or delayed treatment and even death of the patient. The healthcare professionals should be aware that any trauma in the perineal region could lead to FG. PMID- 25135022 TI - Management of ankle sprains during pregnancy: evaluation of 96 cases. AB - BACKGROUND: The aim of this study was to suggest a safe management method for the diagnosis and treatment of ankle sprains in pregnant patients. METHODS: Between November 2005 and January 2013, 96 pregnant patients with ankle sprains referred to the department of orthopedics and traumatology were evaluated, retrospectively. The Ottawa ankle rules were used to assess the need for radiologic evaluation. Radiological procedures: Surface USG, X-ray (0,6 mGy, mortise view), MRI (T1 and STIR) and fluoroscopy with 0,8 mGy/s doses 0,4 ms single shot views in surgery room. The results of the operated patients were evaluated with AOFAS scoring system. RESULTS: Forty-four (45,8%) patients were treated with conservative methods and there was no need for radiological evaluation. USG was used in 17 (17,7%), MRI in 24 (25%), X-ray in 4 (4,1%) and both USG and MRI in 7 (7,2%) patients during diagnosis. An algorithm was created for the diagnosis and treatment of pregnant patients with ankle sprains. No complications due to radiological and surgical procedures occurred over pregnancies. The AOFAS score was 83 (65-100) in the operated patients. CONCLUSION: There is no standard management method for the diagnosis and treatment of pregnant patients with ankle sprains. The algorithm presented in this study may be useful. Good results can be obtained with an appropriate preparation and surgical technique. PMID- 25135023 TI - Retrospective analysis of burn injuries caused by hot milk in 159 pediatric patients: 14 years of experience in a burn unit. AB - BACKGROUND: The aim of this study was to investigate the hot milk burns among the pediatric patients and to compare our experiences with similar studies in the literature. METHODS: A 14-year retrospective study was conducted on 159 pediatric patients with hot milk burn who hospitalized at the Burn Unit of Erciyes University Medical Faculty. RESULTS: There were 81 male and 78 female patients with a male to female ratio of 1.03:1. The mean age of the patients was 2.7+/-1.6 years. The initial injury was immersion in 59.7% of the patients and spillage in 40.3%. The mean burned body surface area of the patients was 18.6+/-10.8%. Twenty two percent of the patients had moderate, and 78% had major burn trauma. Forty nine percent of the patients received burn wound debridement and reconstruction with auto-skin grafts. Our burn unit's mortality rate was 1.5% among 542 pediatric patients with hot water, and 5.6% among 159 pediatric patients with hot milk burn during the same period, respectively. CONCLUSION: Hot milk burns should be considered as separately from other hot liquid burns which do not contain fat such as water, tea, and coffee. Physical and chemical properties of milk because of its high content of fat give rise to more tissue destruction, increased morbidity and mortality. PMID- 25135024 TI - [The results of low profile locking anatomical plate application for the treatment of Edinburg type 2 clavicle diaphysis fractures]. AB - BACKGROUND: Although conservative measures are the general choice of treatment for clavicle fractures; surgery is advised for displaced and multifragmentary fractures. Open reduction and osteosynthesis with a plate-screw combination are used widely as surgical treatment options. METHODS: In our study, there were 21 patients with Edinburgh Type IIB clavicle middiaphysal fractures treated surgically with locked anatomical clavicle plate. RESULTS: Among those 31 patients and 32 clavicle middiaphysal fractures, Seventeen clavicle fractures were right-side, and fifteen were left side. 24 of them were males, 7 of them were females and the mean age was 28 (15-62) years. The mean follow-up period was 12.3 (6-36) months and healing time 15.2 (12-20) weeks. 3 patients with Type IIB fracture had a healing time longer than 12 weeks. As the result of healing patients', mean constant score was 92 (85-98) and DASH score 9 (2-20). There has been a problem due to the implant detected in 3 (9%) patients. DISCUSSION: Successful functional and radiographic results can be achieved as a result of the surgical treatment of the clavicle middiaphysal fractures with locked anatomical plates. PMID- 25135025 TI - Ergotamine-induced vasospastic ischemia mimicking arterial embolism: unusual case. AB - Ergotamine toxicity is an important and rare condition, including tachycardia, arterial spasm which occurring as a result of accidental overdosing or drug interactions. We assessed the consequences of delayed diagnosis of peripheral arterial vasoconstriction occurring after simultaneous macrolide use by a 35-year old woman using an ergot-derived drug for migraine. Diagnosis of ergotamine intoxication begins with suspicion. Interventional radiologists and surgeons should be aware of this acute dangerous condition. PMID- 25135026 TI - Successful surgical rescue of delayed onset diaphragmatic hernia following radiofrequency ablation for hepatocellular carcinoma. AB - Radiofrequency ablation (RFA) has been established as the mainstay therapy for hepatocellular carcinoma (HCC) in patients deemed unsuitable for surgical resection. However, delayed diaphragmatic hernia can occur as a result of this procedure. There have been only seven other cases reported on this complication in the literature. Considering the recent growth in the popularity of the procedure, it is predictable that the incidence of the diaphragmatic hernia, due to RFA, will definitely increase. This case report is therefore vitally important as it increases clinical awareness of this currently rare complication, which could lead to improved survival rates in these patients. This case concerns an 81 year-old Asian man with a past medical history of cirrhosis and HCC (segment IV and VIII) who presented with a delayed, right diaphragmatic hernia and strangulated ileus 18 months after his original RFA procedure. It is important to implement extra measures to limit the risk of diaphragmatic, thermal injuries when RFA is performed. In particular, gastroenterologists, surgeons and accident and emergency staff should all be aware of this complication proceed with rapid diagnosis and management when patients, who previously underwent RFA, present with acute abdominal pain. PMID- 25135027 TI - Surgical treatment of a Malgaigne fracture. AB - Sacral fractures are generally accompanied by pelvic ring fractures. They rarely develop in an isolated form. Sacroiliac dislocation without sacral fracture is extremely rare. We report a case with a sacroiliac dislocation without sacral fracture, which was treated surgically. Lumbopelvic stabilization was applied using iliac wing plates. The case was evaluated according to his clinical condition and visual analogue score (VAS), American Spinal Injury Association (ASIA) and Oswestry scales. Considering the role of the sacrum, which transmits the load of the entire spine to the pelvis, meticulous care must be given to ensure the mechanic stability of the spine when evaluating patients with sacral and pelvic fractures. Very serious spinopelvic instability is present in sacroiliac dislocations even in the absence of sacral fractures. Caudal migration of the sacrum together with the cranial migration of the iliac wings can cause serious pelvic imbalance and difficulties in walking and maintaining a standing position. Aggressive stabilization and fusion are required, and these must be performed in the early period. PMID- 25135028 TI - Thyroid storm due to head injury. AB - In this case report, we would like to present a 36-year-old male patient injured in a street fight without any disease previously known, who was accepted to our intensive care unit with the preliminary diagnoses of minimal cerebral contusion and aspiration pneumonia however by the physical examination, clinical and laboratory findings, was diagnosed as thyroid storm due to trauma. In the current literature, only a few cases reported showing thyroid storm-induced by trauma, and we would like to present the clinical features and management of this life threatening endocrinological emergency. PMID- 25135029 TI - Swallowed a needle stuck in heart. AB - Cardiac tamponade (CT) is a clinical entity characterized by hemodynamic insufficiency resulting from increased intrapericardial pressure due to accumulation of contents such as serous fluid, blood, and pus. CT is a treatable cause of cardiogenic shock, which can be fatal unless diagnosed promptly. Dyspnea, chest pain, hypotension, tachycardia, pulsus paradoxus, raised jugular venous pressure, muffled heart sounds, decreased electrocardiographic voltage, and enlarged cardiac silhouette on chest X-ray are the major clinical signs in CT. Idiopathic or viral pericardititis, iatrogenic trauma during percutaneous coronary interventions or coronary artery bypass grafting, external trauma, malignancies, acute or chronic kidney disease, collagen vascular diseases, tuberculosis, radiation on the chest wall, hypothyroidism and aortic dissection are the etiologic factors. Herein, we present a case of surgically treated CT, which was diagnosed in the third day of ingestion of a sewing needle. PMID- 25135030 TI - [Cross stability in conventional shoes by the use of spring steel insoles: a pedobarographic effect study with observational application]. AB - BACKGROUND: From an orthopedic point of view, wearing conventional ready to wear shoes negatively affects the front transverse arch of the human foot by forcing it into an unnatural inverted position. OBJECTIVES: The aim of the present orthopedic application study was to conduct a standardized assessment of the biomechanical effect of a newly developed, longitudinally flexible and cross stable spring steel insole by means of pedobarographic measurements and by means of a supplementary questioning of the participants. MATERIAL AND METHODS: In order to do this a total of 33 healthy adult participants were recruited in summer 2013. The randomized, blinded and controlled main study compared the cross stable insole made from spring steel with a flat, ordinary control insole made from ethylene vinyl acetate by means of pedobarographic in-shoe measurements at the forefoot. Additionally, the subjectively perceived effect of the steel insole with respect to comfort, restricted mobility and pain was assessed in a randomized, blinded and controlled ancillary study, using a cross-over design. RESULTS: Both the plantar peak pressure and the plantar force-time integral were significantly higher with the spring steel insole, especially in the central forefoot. In the subsequent test phase lasting several weeks during which the participants were asked to wear the spring steel insole, they rarely complained about problems and in particular did not report negative effects regarding comfort, restricted mobility and pain compared to the ordinary control insoles. CONCLUSION: The present study was conducted according to high methodological standards and proved for the first time that the tested spring steel insoles have a positive effect on the human forefoot. The cross stability increases the pressure in the median ball area, prevents the unnatural inverted position of the forefoot and thus creating an effect which is comparable to walking barefoot. As the participants did not judge this orthopedic effect of the cross stability as being uncomfortable, such an insole could be used a millionfold as a primary prevention in conventional shoes. PMID- 25135031 TI - Prevalence of tinea pedis in psoriasis, compared to atopic dermatitis and normal controls--a prospective study. AB - There are discrepancies in the literature regarding the prevalence of tinea pedis in psoriasis. The aim of this investigation was to conduct a cross-sectional study of the prevalence of tinea pedis in psoriasis compared to atopic dermatitis patients and normal controls. We enrolled 232 psoriatic patients, 190 atopic dermatitis patients and 202 normal controls, between the years 2010 and 2013. The prevalence of tinea pedis was 13.8% in psoriasis patients, not significantly different from that in atopic dermatitis patients 8.4% (P = 0.092)), but significantly higher than in normal controls 7.4% (P = 0.043). Both gender and age affected the prevalence of tinea pedis in psoriasis and normal controls, while only age affected the prevalence of tinea pedis in atopic dermatitis. Regarding gender, there was higher prevalence of tinea pedis in men: 19.1% (P = 0.019) in psoriasis and 12.1% (P = 0.013) in normal controls. Age affected the prevalence of tinea pedis in normal controls (P < 0.001), psoriasis patients (P = 0.001) and atopic dermatitis patients (P = 0.001), with higher prevalence with increasing age. Trichophyton rubrum was the most common species in psoriasis (71.9%), atopic dermatitis (75.0%) and normal controls (73.3%). Our study found a relatively high prevalence of tinea pedis among psoriasis patients. PMID- 25135032 TI - Fentanyl sublingual spray for breakthrough pain in cancer patients. AB - Breakthrough pain is a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain. Typically, breakthrough pain has a fast onset and short duration, and a significant impact on patients' quality of life. Normal-release oral opioids are the traditional pharmacological approach for patients who are receiving an around the clock opioid regimen; however, their onset and duration of action may not be suitable for treating many breakthrough pains. Efforts to provide nonparenteral opioid formulations that could provide more rapid, and more effective, relief of breakthrough pain have led to the development of transmucosal opioid formulations including fentanyl sublingual spray (FSLS). This is a formulation of fentanyl available in doses of 100, 200, 400, 600, and 800 MUg strengths approved for the management of breakthrough pain in adult cancer patients already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Published pharmacokinetic, efficacy, tolerability, and safety data suggest that FSLS has a valuable role to play in the symptomatic pharmacological management of breakthrough pain. The effective dose of FSLS is determined by titration according to the needs of the individual patient. PMID- 25135033 TI - Review of lidocaine/tetracaine cream as a topical anesthetic for dermatologic laser procedures. AB - There are multiple different topical anesthetic options available to minimize the pain associated with cosmetic dermatologic procedures. These options, either alone or in combination, have diverse profiles for effectiveness, ease of use, application time, need for occlusion, and side effects. The lidocaine/tetracaine cream (Pliaglis((r)), Galderma Laboratories, Texas, USA), one of the newer combination options, offers effective pain alleviation that has been evaluated in numerous clinical trials. This combination anesthetic is associated with a very favorable profile because of its ease of use and mild side effects compared to other topical local anesthetics. An overview of available topical local anesthetics will be provided with an outline of clinical study characteristics and results regarding the use of lidocaine/tetracaine cream. PMID- 25135035 TI - Randomized study of pregabalin in patients with cancer-induced bone pain. AB - INTRODUCTION: Improvements are needed in the management of cancer-induced bone pain (CIBP). The objective of this study was to assess the efficacy and safety of pregabalin compared with placebo in the adjunctive treatment of patients with moderate to severe CIBP who were receiving opioids. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, 152 adults diagnosed with a malignant, solid tumor with metastases to bone were randomized to flexible-dose pregabalin (100, 150, 300, or 600 mg/day) or placebo, as add-on to stable opioid analgesic therapy, which was optimized prior to the start of the study. The primary efficacy endpoint was the duration-adjusted average change (DAAC) from baseline in the daily worst pain at the reference site (measured by 11-point numeric rating scale [NRS]) during the fixed-dosage phase. The study was terminated early following an interim analysis that indicated an increase in sample size would be needed to satisfy statistical assumptions for the primary endpoint. Given the early termination of the study, only descriptive analyses were performed. RESULTS: The mean (standard deviation) DAAC from baseline in NRS score for the primary endpoint favored pregabalin treatment: -1.53 (1.81) in the pregabalin group and -1.23 (1.74) in the placebo group. Mean DAAC for average pain and sleep interference (NRS) also favored pregabalin. More patients treated with pregabalin reported improvement ("very much improved," "much improved," or "minimally improved") based on Patient Global Impression of Change: 81.4% compared with 70.0% in the placebo group. CONCLUSION: Data from this study indicate that pregabalin use may reduce metastatic bone pain. Due to the incomplete analysis, further study of pregabalin in the management of CIBP is required. PMID- 25135036 TI - Predictive value of lidocaine for treatment success of oxcarbazepine in patients with neuropathic pain syndrome. AB - INTRODUCTION: Pharmacotherapy in patients with neuropathic pain syndromes (NPS) can be associated with long periods of trial and error before reaching satisfactory analgesia. The aim of this study was to investigate whether a short intravenous (i.v.) infusion of lidocaine may have a predictive value for the efficacy of oxcarbazepine. METHODS: In total, 16 consecutive patients with NPS were studied in a prospective, uncontrolled, open-label study design. Each patient received i.v. lidocaine (5 mg/kg) within 30 min followed by a long-term oral oxcarbazepine treatment (900-1,500 mg/day). During an observation period of 28 days, treatment response was documented by a questionnaire including the average daily pain score documented on a numeric rating scale (NRS). RESULTS: A total of 6 out of 16 patients (38%) were lidocaine responders (defined as pain reduction >50% during the infusion), and 4 of 16 (25%) were oxcarbazepine responders. In total, 6 out of 16 participants (38%) discontinued oxcarbazepine treatment due to side effects. In an interim analysis predictive value of the lidocaine infusion was low with a Kendall's tau correlation coefficient of 0.29 and coefficient of determination R(2) of 0.119 (95% confidence interval -0.29 to 0.72). As a consequence of this low correlation, the study was discontinued for ethical reasons. CONCLUSION: In conclusion, lidocaine infusion has a low predictive value for effectiveness of oxcarbazepine-if at all. PMID- 25135034 TI - Myofascial pain syndrome: a treatment review. AB - Myofascial pain syndrome (MPS) is defined as pain that originates from myofascial trigger points in skeletal muscle. It is prevalent in regional musculoskeletal pain syndromes, either alone or in combination with other pain generators. The appropriate evaluation and management of myofascial pain is an important part of musculoskeletal rehabilitation, and regional axial and limb pain syndromes. This article reviews the current hypotheses regarding the treatment modalities for myofascial trigger points and muscle pain. Through a critical evidence-based review of the pharmacologic and nonpharmacologic treatments, the authors aim to provide clinicians with a more comprehensive knowledge of the interventions for myofascial pain. PMID- 25135037 TI - Effects of a single session group intervention for pain management in chronic pain patients: a pilot study. AB - INTRODUCTION: Behavioral and psychological interventions are key components of treating chronic pain. However, there are logistical barriers to providing such treatments, including a lack of psychological staff to provide such interventions and limited ability of patients with chronic pain to attend multiple sessions. As other areas of mental health have shown promise in providing single session interventions for various conditions, this pilot study hypothesized that a single group session for chronic pain patients could be helpful in decreasing patient pain catastrophizing. The five content areas addressed in the group were termed understanding, accepting, calming, balancing, and coping. METHODS: A pilot study was undertaken. Chronic pain patients were given a pre-group assessment, including the Pain Catastrophizing Scale with a follow-up assessment administered 3 months later. RESULTS: Fifty-three patients were studied. Results showed a significant decrease in overall pain catastrophizing scores at follow-up. A clear majority of patients also reported that the group was helpful and should be offered to other pain patients. CONCLUSION: This study suggests that a single session group can be a helpful intervention for patients with chronic pain. PMID- 25135039 TI - Erratum to: Review of Lidocaine/Tetracaine Cream as a Topical Anesthetic for Dermatologic Laser Procedures. PMID- 25135038 TI - Interpreting effect sizes and clinical relevance of pharmacological interventions for fibromyalgia. AB - Duloxetine, milnacipran, and pregabalin are approved by the United States Food and Drug Administration for the management of fibromyalgia. A number of meta analyses, pooled analyses, and systematic reviews have been published in recent years involving the efficacy of these three medications for pain in fibromyalgia. Despite being based on the same clinical data, some analyses found these treatments to have a clinically relevant effect on pain, while others concluded that the advantages were small or of questionable clinical relevance. This commentary discussed possible reasons behind these differing conclusions and explored ways of evaluating the clinical relevance of pharmacological treatments for fibromyalgia. In particular, we considered: (1) the importance of judicious and careful interpretation of average treatment effect size and the recognition that average treatment effect sizes do not always tell the whole story; (2) the utility of individual patient response data to assess clinical relevance; and (3) the importance of considering pain reduction within the context of other benefits due to the presence of associated symptoms in patients with fibromyalgia. PMID- 25135040 TI - Transcutaneous vagal nerve stimulation may elicit anti- and pro-nociceptive effects under experimentally-induced pain - a crossover placebo-controlled investigation. AB - Vagal nerve stimulation is a promising method for the treatment of pain. The aim was to investigate the effect of non-invasive transcutaneous vagal nerve stimulation (TVNS) on the experimental pain threshold (PT) and to compare it with placebo. PT of standardized electrical stimulation was measured in 22 healthy male volunteers during two study sessions. TVNS was applied to the auricular concha bilaterally for 35min using 2Hz/100Hz bursts with the intensity, which was individually maximal but non-painful. During the placebo session, the volunteers received no stimulation. PT, heart rate and blood pressure were registered as outcome measures. There were no differences in PT values between TVNS and placebo conditions in the group analysis. Fifteen volunteers (responders) reacted with an increase in PT during TVNS (p<0.01 vs. baseline) but not during the placebo session. Another six participants reported decreased PT during and after TVNS (p<0.05 vs. baseline), but not during the placebo session. Heart rate and blood pressure did not change during the study. Transcutaneous vagal nerve stimulation may produce both anti- and pro-nociceptive effects in healthy volunteers. The individual sensitivity and TVNS parameters might play a role. PMID- 25135041 TI - [Epigenetic modifications in autoimmune diseases]. PMID- 25135042 TI - [Obituary for Prof. Dr. med. Fritz Schilling (1919-2014)]. PMID- 25135044 TI - Infectious Endocarditis in 49-Year-Old Man and Discussion of Phenotypic Characteristics of Aerococcus urinae and Viridans Streptococci. AB - PATIENT: 49 year-old man. CHIEF COMPLAINT: Dyspnea at rest and dyspnea on exertion. HISTORY OF PRESENT ILLNESS: Diagnosed with upper respiratory tract infection 10 days previously. PAST MEDICAL HISTORY: Obese (BMI not available), but no significant past medical history. SOCIAL HISTORY: Noncontributory. FAMILY HISTORY: Noncontributory. PMID- 25135046 TI - Writing style: abstract thoughts. PMID- 25135045 TI - First report of bacteremia by Janibacter terrae in humans. AB - The genus Janibacter comprises nine different species mainly found in the environment. Only two human infections by these microorganisms have been previously reported, one by J. melonis and another one by an undescribed Janibacter sp. Herewith we report the first human cases of infection by J. terrae in four bacteremic patients. The microorganisms were isolated from two consecutive blood cultures taken from four febrile patients with several underlying conditions. All patients were treated with antibiotics, two of them with favorable outcome. Two severely immunocompromised patients died, and one was treated with an antibiotic in vitro active against the isolate. Janibacter terrae was identified by phenotypic and 16S rDNA amplification methods. This report includes also the first data on antimicrobial susceptibility of this opportunistic pathogen. Clinical microbiologists should be aware of this microorganism which can be identified by phenotypic and molecular methods. PMID- 25135047 TI - Biomarkers in atopic dermatitis: it is time to stratify. PMID- 25135048 TI - Profibrotic agents for venous malformations? PMID- 25135049 TI - Epidemiology of hand eczema from adolescence to adulthood. PMID- 25135054 TI - FeP nanoparticles grown on graphene sheets as highly active non-precious-metal electrocatalysts for hydrogen evolution reaction. AB - A synthetic route to FeP-GS hybrid sheets that show good stability and high electrocatalytic activity for hydrogen evolution reaction is reported. The materials are prepared via thermal phosphidation of pre-synthesized Fe3O4-GS hybrid sheets. PMID- 25135053 TI - Patient perspective on remote monitoring of cardiovascular implantable electronic devices: rationale and design of the REMOTE-CIED study. AB - BACKGROUND: Remote patient monitoring is a safe and effective alternative for the in-clinic follow-up of patients with cardiovascular implantable electronic devices (CIEDs). However, evidence on the patient perspective on remote monitoring is scarce and inconsistent. OBJECTIVES: The primary objective of the REMOTE-CIED study is to evaluate the influence of remote patient monitoring versus in-clinic follow-up on patient-reported outcomes. Secondary objectives are to: 1) identify subgroups of patients who may not be satisfied with remote monitoring; and 2) investigate the cost-effectiveness of remote monitoring. METHODS: The REMOTE-CIED study is an international randomised controlled study that will include 900 consecutive heart failure patients implanted with an implantable cardioverter defibrillator (ICD) compatible with the Boston Scientific LATITUDE(r) Remote Patient Management system at participating centres in five European countries. Patients will be randomised to remote monitoring or in-clinic follow-up. The In-Clinic group will visit the outpatient clinic every 3 6 months, according to standard practice. The Remote Monitoring group only visits the outpatient clinic at 12 and 24 months post-implantation, other check-ups are performed remotely. Patients are asked to complete questionnaires at five time points during the 2-year follow-up. CONCLUSION: The REMOTE-CIED study will provide insight into the patient perspective on remote monitoring in ICD patients, which could help to support patient-centred care in the future. PMID- 25135055 TI - Synthesis of benzimidazole[2.1-b][1,3]oxazine spirooxindoles via three-component reaction of N-benzylbenzimidazole, acetylenedicarboxylates, and N-alkylisatins. AB - The three-component reaction of N-benzylbenzimidazole, dialkyl acetylenedicarboxylate, and N-alkylisatins in tetrahydrofuran at room temperature afforded the novel functionalized benzimidazole[2.1-b][1,3]oxazine spirooxindoles in good yields. (1)H NMR spectra indicated that two diastereoisomers with a ratio of 1:3-1:6 exist in the obtained spirooxindole derivatives. PMID- 25135056 TI - Neurophysiological assessment of the injured spinal cord: an intraoperative approach. AB - STUDY DESIGN: Prospective, observational study. OBJECTIVES: To assess the spinal cord function intraoperatively in subjects during spine stabilization for spinal cord trauma, by recording muscular (m-MEPs) and epidural motor evoked potentials (e-MEPs, D wave) along with cortical and epidural somatosensory evoked potentials (e-SEPs) and predicting the outcome of spinal cord injury (SCI). SETTING: Regional Trauma Center, Torino, Italy. METHODS: Fifty-five patients were intraoperatively studied during posterior spine stabilization surgery for traumatic SCI. In all, 21 of these had complete SCI, 14 an incomplete SCI-6 of them with central cord syndrome and 1 with central cord plus Brown Sequard syndrome-and 20 patients were neurologically uncompromised. RESULTS: The neurophysiologic profile of the complete SCI was the absence of both m-MEPs and e MEPs caudally to the lesion site, associated with a lack of cortical and e-SEPs cranially to the lesion site. None of these patients recovered motor function in the follow-up. A clearly detectable caudal D wave was associated with motor recovery even in deeply paraparetic patients. In one neurologically incomplete patient a reversible deterioration of m-MEPs and e-MEPs was observed during the compression-distraction manoeuvre. CONCLUSION: Intraoperative neurophysiological evaluation of SCI patients can provide information about spinal cord function that is not retrievable by other clinical means and can correctly predict neurological outcome. Intraoperative testing during early stabilization of the spine of deeply paraparetic SCI patients provides additional information about their neurological profile. PMID- 25135057 TI - Use of screening to recruitment ratios as a tool for planning and implementing spinal cord injury rehabilitation research. AB - STUDY DESIGN: Descriptive report. OBJECTIVES: To describe screening to recruitment (S:R) ratios and discuss their use for planning and implementing research among individuals with spinal cord injury (SCI) . SETTING: Toronto, Ontario, Canada. METHODS: We calculated S:R ratios for SCI research by study methodology and nature of the exposure/intervention for 25 studies previously conducted in a tertiary SCI rehabilitation facility. Study methodologies included ten randomized controlled trials (RCTs), nine cohort studies and six panel studies. Exposures included seven rehabilitation interventions, and three drug studies, ten telephone interviews/chart abstractions (TI/CA) and five surveys. A S:R ratio was calculated for each study methodology, and exposure type, by dividing the number of consenting individuals who underwent screening by the number of eligible recruited participants enrolled in the study. RESULTS: In terms of design, RCTs had the highest median S:R ratio (3:1), followed by cohort studies (2:1) and panel studies (2:1). In terms of intervention type, drug studies had the largest median S:R ratio (5:1), followed in descending order by rehabilitation studies (2:1), TI/CAs studies (2:1) and surveys (2:1). CONCLUSIONS: Reported S:R ratios varied substantially with study methodology and the associated study intervention exposure. Awareness of S:R ratios may assist researchers in estimating recruitment timelines, personnel needs and study budgets for a required sample size based on the planned study methodology and intended study exposure. We advocate for the routine reporting of S:R ratios to inform the success of future SCI research. PMID- 25135059 TI - GFR may not accurately predict aspects of proximal tubule drug handling. AB - PURPOSE: Dose modification in renal impairment has traditionally been based on changes in estimated glomerular filtration rate (eGFR; estimated by creatinine clearance). However, many drugs are eliminated by tubular anionic and cationic transport where changes in eGFR may not necessarily reflect changes in tubular function. This study investigated the relationship between GFR and renal tubular function with reference to drug handling by using accepted drug probes. METHODS: Three drug probes, (51)Cr-EDTA, fluconazole, and pindolol, were administered to patients who had varying degrees of renal impairment. Blood sampling, assays, and a pharmacokinetic analysis were performed for all drug probes and endogenous urate. Measured GFR ((51)Cr-EDTA clearance; mGFR) was compared to tubular anionic transport (urate clearance), tubular reabsorption (fluconazole clearance), and tubular cationic transport (S-pindolol clearance). RESULTS: A moderately strong association was demonstrated between the measured isotopic GFR and creatinine clearance (R(2) = 0.78). A moderate positive correlation was found between mGFR and proximal tubular anion transport and reabsorption (R(2) = 0.40-0.44, p < 0.0001). In contrast, cationic secretion correlated poorly with mGFR (R(2) = 0.11, p = 0.036). CONCLUSIONS: Given that drug dosing schedules utilise eGFR values as the basis for modifying drug dosing, our results would suggest that a recommendation of a dose reduction according to eGFR alone should be treated with caution. PMID- 25135058 TI - Deglycosylation of mAb by EndoS for improved molecular imaging. AB - PURPOSE: Monoclonal antibodies (mAbs) have been shown preclinically as reliable targeting moieties for antigen imaging using near-infrared fluorescence (NIRF) molecular imaging. However, crystallizable fragment-gamma receptor (FcgammaRs) expressed on immune cells also bind mAbs through defined epitopes on the constant fragment (Fc) of IgG. Herein, we evaluate the potential impact Fc interactions have on mAb agent imaging specificity. PROCEDURE: Through the removal of conserved glycans within the Fc domain, shown to have Fc/FcgammaR interactions, we evaluate their impact on non-specific binding/accumulation of a NIRF-labeled mAb-based imaging agent in lymph nodes (LNs) in inflamed animals and in an orthotopic prostate cancer animal model of LN metastasis. RESULTS: Deglycosylation of a murine mAb against the human epithelial cell adhesion marker using endoglycosidase EndoS significantly reduced non-specific binding in the LNs of inflamed animals and in cancer-negative LNs of tumor-bearing animals. Sensitivity remained unchanged while improvement in imaging specificity increased imaging accuracy. CONCLUSION: The reduction of non-specific binding through deglycosylation of a mAb-based imaging agent shows that reducing Fc/FcgammaR interactions can improve imaging accuracy. PMID- 25135060 TI - Efficacy and safety of creatine supplementation in childhood-onset systemic lupus erythematosus: a randomized, double-blind, placebo-controlled, crossover trial. AB - INTRODUCTION: Creatine supplementation has emerged as a promising non pharmacological therapeutic strategy to counteract muscle dysfunction and low lean mass in a variety of conditions, including in pediatric and rheumatic diseases. The objective of this study was to examine the efficacy and safety of creatine supplementation in childhood systemic lupus erythematosus (C-SLE). METHODS: C-SLE patients with mild disease activity (n = 15) received placebo or creatine supplementation in a randomized fashion using a crossover, double-blind, repeated-measures design. The participants were assessed at baseline and after 12 weeks in each arm, interspersed by an eight-week washout period. The primary outcomes were muscle function, as assessed by a battery of tests including one maximum repetition (1-RM) tests, the timed-up-and-go test, the timed-stands test, and the handgrip test. Secondary outcomes included body composition, biochemical markers of bone remodeling, aerobic conditioning, quality of life, and physical capacity. Possible differences in dietary intake were assessed by three 24-hour dietary recalls. Muscle phosphorylcreatine content was measured through phosphorus magnetic resonance spectroscopy (31 P-MRS). The safety of the intervention was assessed by laboratory parameters, and kidney function was measured by (51)Cr-EDTA clearance. Additionally, self-reported adverse events were recorded throughout the trial. RESULTS: Intramuscular phosphorylcreatine content was not significantly different between creatine and placebo before or after the intervention (creatine-Pre: 20.5 +/- 2.6, Post: 20.4 +/- 4.1, placebo Pre: 19.8 +/- 2.0; Post: 20.2 +/- 3.2 mmol/kg wet muscle; p = 0.70 for interaction between conditions). In addition, probably as a consequence of the lack of change in intramuscular phosphorylcreatine content, there were no significant changes between placebo and creatine for any muscle function and aerobic conditioning parameters, lean mass, fat mass, bone mass, and quality of life scores (p > 0.05). The (51)Cr-EDTA clearance was not altered by creatine supplementation and no side effects were noticed. CONCLUSION: A 12-week creatine supplementation protocol at 0.1 g/kg/d is well tolerated and free of adverse effects but did not affect intramuscular phosphorylcreatine, muscle function, free-fat mass or quality of life in non-active C-SLE patients. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT01217320. PMID- 25135061 TI - Oral pigmentation is a specific feature of lupus erythematosus. PMID- 25135062 TI - Intramyocardial injection of hypoxia-preconditioned adipose-derived stromal cells treats acute myocardial infarction: an in vivo study in swine. AB - Hypoxic preconditioning is a promising method for improving the anti-apoptotic and paracrine signaling capabilities of adipose-derived stromal cells (ADSCs). The purpose of this study was to analyze the influence of different hypoxic conditions on ADSCs and the therapeutic effects of hypoxia-preconditioned ADSCs (HPADSCs) on an animal model of myocardial infarction (MI). For the in vitro studies, ADSCs were divided into five groups and cultured in different oxygen concentrations (1, 3, 5, 10, and 21 %). After 24 h, RT-PCR and western blots showed that 3 % oxygen preconditioning could improve the viability and cytokine secretion of the ADSCs. A Matrigel assay indicated that the HPADSC-conditioned medium could stimulate endothelial cells to form capillary-like tubes. For the in vivo studies, MI was induced by coronary occlusion in 24 mature Chinese minipigs. The animals were divided into three groups and treated by intramyocardial injection with vehicle alone (saline group), with 1 * 10(8) ADSCs cultured in normoxic conditions (ADSCs group) or with 1 * 10(8) ADSCs precultured in 3 % oxygen (HPADSCs group). SPECT and echocardiography demonstrated that cardiac function was improved significantly in the HPADSC transplant group compared with the vehicle control group (P < 0.05). Immunofluorescence showed fewer apoptotic cells and more small- to medium-sized vessels in the HPADSC transplantation group (P < 0.05). Three percent oxygen is the optimum preconditioning treatment for ADSCs. HPADSC transplantation can prevent ventricular remodeling and reduce the infarct size. PMID- 25135065 TI - The mechanism of Menshutkin reaction in gas and solvent phases from the perspective of reaction electronic flux. AB - The mechanism of Menshutkin reaction, NH(3) + CH(3)Cl = [CH(3)-NH(3)]+ + Cl-, has been thoroughly studied in both gas and solvent (H(2)O and cyclohexane) phase. It has been found that solvents favor the reaction, both thermodynamically and kinetically. The electronic activity that drives the mechanism of the reaction was identified, fully characterized, and associated to specific chemical events, bond forming/breaking processes, by means of the reaction electronic flux. This led to a complete picture of the reaction mechanism that was independently confirmed by natural bond-order analysis and the dual descriptor for chemical reactivity and selectivity along the reaction path. PMID- 25135066 TI - Accurate calculation of the ionization energies of the chlorine lone pairs in 1,1,1-trifluoro-2-chloroethane (HCFC-133a). AB - The vertical ionization energies of the chlorine lone pairs in HCFC-133a have been calculated at the SCF (via Koopmans' theorem and including orbital relaxation) and correlated (ROMP2, OVGF, and ROCCSD(T)) levels. Dunning aug-cc pVXZ (X = D, T, and Q) basis sets were employed, and the ROMP2 and ROCCSD(T) results were extrapolated to the complete basis set (CBS) limit. Our highest level results (obtained at the ROCCSD(T)/CBS level) were 11.99 and 12.08 eV for the Cl lone pairs of A" and A' symmetry, respectively. The values obtained at the computationally much less demanding ROMP2/CBS level were just 0.10 and 0.13 eV higher than the highest-level ones. Using the Cl lone-pair band of the photoelectron spectrum of the HCF(2)Cl and CF(3)Cl molecules as a guide, it is considered very unlikely that these two lone pairs can be discriminated in the photoelectron spectrum of the title molecule. The use of the calculated IPs to estimate the energies of the Rydberg states of HCFC-133a is also discussed. PMID- 25135064 TI - The MyPEEPS randomized controlled trial: a pilot of preliminary efficacy, feasibility, and acceptability of a group-level, HIV risk reduction intervention for young men who have sex with men. AB - An exigent need exists for HIV prevention intervention research targeting young men who have sex with men (MSM)-a group of young adults that, despite composing the highest and most racially disproportionate rates of HIV incidence, have been least often the focus of behavioral intervention research. This pilot study tested a group-based HIV primary prevention intervention for young MSM to evaluate its initial efficacy, feasibility, and acceptability. Participants were randomized (N = 101; aged 16-20 years) to one of two group-level, HIV and STI education programs: controls participated in a non-interactive, lecture-based program, while intervention participants took part in a highly interactive program tailored to young MSM aged 16-20. Sexual risk and social cognitive outcomes were assessed at baseline, 6-, and 12-weeks post-intervention. Over the entire follow-up period, intervention participants were less likely than controls to engage in any sexual behavior while under the influence of substances (p < .05), and a decreasing trend in unprotected anal sex while under the influence of substances was also observed in this group (p = .08). Follow-up differences between groups on social cognitive outcomes favored the intervention group, though these differences were non-significant. Acceptability ratings were modest. A 6-session behavioral intervention tailored to young MSM, aged 16-20, is feasible, acceptable, and demonstrates evidence of preliminary efficacy in reducing sexual risk, specifically sexual risk while under the influence of substances. PMID- 25135067 TI - Conformational analysis of glutamic acid: a density functional approach using implicit continuum solvent model. AB - Amino acids are constituents of proteins and enzymes which take part almost in all metabolic reactions. Glutamic acid, with an ability to form a negatively charged side chain, plays a major role in intra and intermolecular interactions of proteins, peptides, and enzymes. An exhaustive conformational analysis has been performed for all eight possible forms at B3LYP/cc-pVTZ level. All possible neutral, zwitterionic, protonated, and deprotonated forms of glutamic acid structures have been investigated in solution by using polarizable continuum model mimicking water as the solvent. Nine families based on the dihedral angles have been classified for eight glutamic acid forms. The electrostatic effects included in the solvent model usually stabilize the charged forms more. However, the stability of the zwitterionic form has been underestimated due to the lack of hydrogen bonding between the solute and solvent; therefore, it is observed that compact neutral glutamic acid structures are more stable in solution than they are in vacuum. Our calculations have shown that among all eight possible forms, some are not stable in solution and are immediately converted to other more stable forms. Comparison of isoelectronic glutamic acid forms indicated that one of the structures among possible zwitterionic and anionic forms may dominate over the other possible forms. Additional investigations using explicit solvent models are necessary to determine the stability of charged forms of glutamic acid in solution as our results clearly indicate that hydrogen bonding and its type have a major role in the structure and energy of conformers. PMID- 25135068 TI - Investigations into the nature of halogen- and hydrogen-bonding interactions of some heteroaromatic rings with dichlorine monoxide. AB - We have studied the structures, properties, and nature of halogen- and hydrogen bonding interactions between some heteroaromatic rings (C(5)H(5)N, C(4)H(4)O, and C(4)H(4)S) with Cl(2)O at the MP2/aug-cc-pVTZ level. We also considered the solvent effect on the halogen bonds and hydrogen bonds in the C(5)H(5)N-Cl(2)O complexes and found that the solvent has a weakening effect on the pi-type halogen bond and hydrogen bond but a prominent enhancing effect on sigma-type halogen bond. The complexes have also been analyzed with symmetry adapted perturbation theory method (SAPT). PMID- 25135069 TI - Current resources for evidence-based practice, September/October 2014. PMID- 25135071 TI - Insight into curcumin-loaded beta-lactoglobulin nanoparticles: incorporation, particle disintegration, and releasing profiles. AB - This study aimed at developing protein nanoparticles with desirable loading efficiency (LE) and low cross-linker concentration. Using beta-lactoglobulin (BLG) and curcumin as a model system, this work demonstrated that the LE could be improved by up to 157% by maintaining low antisolvent content before mild evaporation. Moreover, the optimal level of glutaraldehyde decreased by 50% as the curcumin/protein ratio increased, suggesting that toxic cross-linkers could be partly replaced with natural phenols such as curcumin. The BLG-curcumin nanoparticles showed average size of 164-214 nm, zeta potential of -42 mV, and LE of up to 11%. Interestingly, BLG nanoparticles demonstrated rapid disintegration and nutraceutical release in simulated gastric fluid (SGF) at pH 2, despite the known resistance of BLG against pepsin. However, they maintained integrity in SGF at pH 5. This phenomenon, followed by extensive degradation in simulated intestinal fluid, suggested the controlled-release property of BLG nanoparticles when administered orally. PMID- 25135070 TI - A malaria vaccine candidate based on an epitope of the Plasmodium falciparum RH5 protein. AB - BACKGROUND: The Plasmodium falciparum protein RH5 is an adhesin molecule essential for parasite invasion of erythrocytes. Recent studies show that anti PfRH5 sera have potent invasion-inhibiting activities, supporting the idea that the PfRH5 antigen could form the basis of a vaccine. Therefore, epitopes recognized by neutralizing anti-PfRH5 antibodies could themselves be effective vaccine immunogens if presented in a sufficiently immunogenic fashion. However, the exact regions within PfRH5 that are targets of this invasion-inhibitory activity have yet to be identified. METHODS: A battery of anti-RH5 monoclonal antibodies (mAbs) were produced and screened for their potency by inhibition of invasion assays in vitro. Using an anti-RH5 mAb that completely inhibited invasion as the selecting mAb, affinity-selection using random sequence peptide libraries displayed on virus-like particles of bacteriophage MS2 (MS2 VLPs) was performed. VLPs were sequenced to identify the specific peptide epitopes they encoded and used to raise specific antisera that was in turn tested for inhibition of invasion. RESULTS: Three anti-RH5 monoclonals (0.1 mg/mL) were able to inhibit invasion in vitro by >95%. Affinity-selection with one of these mAbs yielded a VLP which yielded a peptide whose sequence is identical to a portion of PfRH5 itself. The VLP displaying the peptide binds strongly to the antibody, and in immunized animals elicits an anti-PfRH5 antibody response. The resulting antisera against the specific VLP inhibit parasite invasion of erythrocytes more than 90% in vitro. CONCLUSIONS: Here, data is presented from an anti-PfRH5 mAb that completely inhibits erythrocyte invasion by parasites in vitro, one of the few anti-malarial monoclonal antibodies reported to date that completely inhibits invasion with such potency, adding to other studies that highlight the potential of PfRH5 as a vaccine antigen. The specific neutralization sensitive epitope within RH5 has been identified, and antibodies against this epitope also elicit high anti-invasion activity, suggesting this epitope could form the basis of an effective vaccine against malaria. PMID- 25135072 TI - Canadian Society for Exercise Physiology position stand: Benefit and risk for promoting childhood physical activity. AB - Current guidelines recommend children accumulate 60 min of daily physical activity; however, highly publicized sudden-death events among young athletes raise questions regarding activity safety. An expert group convened (June 2012) to consider the safety of promoting increased physical activity for children, and recommended the publication of an evidence-based statement of current knowledge regarding the benefits and risks of physical activity for children. Recommendations for encouraging physical activity while maximizing the opportunity to identify children who have been prescribed a physical activity restriction include (1) professionals and (or) researchers that encourage children to change the type of physical activity or to increase the frequency, intensity, or duration of their activity should inquire whether a child has primary healthcare provider-prescribed activity limitations before the child's activity participation changes; (2) physical activity researchers should prioritize the development of evidence regarding the benefits and risks of childhood physical activity and inactivity, particularly data on the risks of sedentary lifestyles and physical activity-associated injury risks that accounts for the amount of activity performed, and the effectiveness of current risk management strategies and screening approaches; (3) professionals and researchers should prioritize the dissemination of information regarding the benefits of physical activity and the risks of sedentary behaviour in children; and (4) parents and professionals should encourage all children to accumulate at least 60 min of physical activity daily. The recommendations are established as a minimum acceptable standard that is applicable to all physical activity opportunities organized for children, whether those opportunities occur in a community, school, or research setting. PMID- 25135073 TI - Summary report of the International Association of Neurorestoratology VII Conference: regulations, ethics, science, and the need of patients care in neurorestoratology. PMID- 25135075 TI - Experimental evaluation of a Markov multizone model of particulate contaminant transport. AB - The performance of a Markov chain model of the three-dimensional transport of particulates in indoor environments is evaluated against experimentally measured supermicrometer particle deposition. Previously, the model was found to replicate the predictions of relatively simple particle transport and fate models; and this work represents the next step in model evaluation. The experiments modeled were (i) the release of polydispersed particles inside a building lobby, and (ii) the release of monodispersed fluorescein-tagged particles inside an experimental chamber under natural and forced mixing. The Markov model was able to reproduce the spatial patterns of particle deposition in both experiments, though the model predictions were sensitive to the parameterization of the particle release mechanism in the second experiment. Overall, the results indicate that the Markov model is a plausible tool for modeling the fate and transport of supermicrometer particles. PMID- 25135074 TI - Perceived neighbourhood social cohesion and myocardial infarction. AB - BACKGROUND: The main strategy for alleviating heart disease has been to target individuals and encourage them to change their health behaviours. Although important, emphasis on individuals has diverted focus and responsibility away from neighbourhood characteristics, which also strongly influence people's behaviours. Although a growing body of research has repeatedly demonstrated strong associations between neighbourhood characteristics and cardiovascular health, it has typically focused on negative neighbourhood characteristics. Only a few studies have examined the potential health enhancing effects of positive neighbourhood characteristics, such as perceived neighbourhood social cohesion. METHODS: Using multiple logistic regression models, we tested whether higher perceived neighbourhood social cohesion was associated with lower incidence of myocardial infarction. Prospective data from the Health and Retirement Study--a nationally representative panel study of American adults over the age of 50--were used to analyse 5276 participants with no history of heart disease. Respondents were tracked for 4 years and analyses adjusted for relevant sociodemographic, behavioural, biological and psychosocial factors. RESULTS: In a model that adjusted for age, gender, race, marital status, education and total wealth, each SD increase in perceived neighbourhood social cohesion was associated with a 22% reduced odds of myocardial infarction (OR=0.78, 95% CI 0.63 to 0.94. The association between perceived neighbourhood social cohesion and myocardial infarction remained even after adjusting for behavioural, biological and psychosocial covariates. CONCLUSIONS: Higher perceived neighbourhood social cohesion may have a protective effect against myocardial infarction. PMID- 25135076 TI - An empirical analysis of thermal protective performance of fabrics used in protective clothing. AB - Fabric-based protective clothing is widely used for occupational safety of firefighters/industrial workers. The aim of this paper is to study thermal protective performance provided by fabric systems and to propose an effective model for predicting the thermal protective performance under various thermal exposures. Different fabric systems that are commonly used to manufacture thermal protective clothing were selected. Laboratory simulations of the various thermal exposures were created to evaluate the protective performance of the selected fabric systems in terms of time required to generate second-degree burns. Through the characterization of selected fabric systems in a particular thermal exposure, various factors affecting the performances were statistically analyzed. The key factors for a particular thermal exposure were recognized based on the t-test analysis. Using these key factors, the performance predictive multiple linear regression and artificial neural network (ANN) models were developed and compared. The identified best-fit ANN models provide a basic tool to study thermal protective performance of a fabric. PMID- 25135078 TI - Review of neurodevelopmental treatment. PMID- 25135077 TI - Calprotectin (S100A8/9) as serum biomarker for clinical response in proof-of concept trials in axial and peripheral spondyloarthritis. AB - INTRODUCTION: Biomarkers complementing clinical evaluations may help to reduce the length and size of proof-of-concept (PoC) trials aimed to obtain quick "go/no go" decisions in the clinical development of new treatments. We aimed to identify and validate serum biomarkers with a high sensitivity to change upon effective treatment in spondyloarthritis (SpA) PoC trials. METHODS: The candidate biomarkers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase 3 (MMP-3), calprotectin, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA) in healthy controls (n = 20) and SpA patients before and after 2 weeks of infliximab (n = 18) or placebo (n = 19) treatment in cohort 1. Clinical outcome was evaluated at week 12. Results were validated in ankylosing spondylitis (AS) with infliximab (cohort 2, n = 21) and peripheral SpA with etanercept (cohort 3, n = 20). RESULTS: Serum levels of calprotectin, hs-CRP, PTX-3, VEGF (all P < 0.001) and MMP-3 (P = 0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy controls. Treatment with infliximab, but not placebo, significantly decreased calprotectin (P < 0.001) and hs-CRP (P < 0.001) levels, with a similar trend for MMP-3 (P = 0.063). The standardized response mean (SRM), which reflects the ability to detect changes over time, was high for calprotectin (-1.26), good for hs-CRP (-0.96) and moderate for MMP-3 (-0.52). Calprotectin and hs-CRP, but not MMP-3, were good biomarkers for treatment response in axial and peripheral SpA as evaluated and confirmed in cohort 2 and 3 respectively. CONCLUSIONS: Calprotectin and hs-CRP are good serum biomarkers with high sensitivity to change upon effective treatment at the group level in small-scale, short term PoC trials in SpA. PMID- 25135079 TI - The biology of pulmonary aspergillus infections. AB - Pulmonary aspergillus infections are mainly caused by Aspergillus fumigatus and can be classified based on clinical syndromes into saphrophytic infections, allergic disease and invasive disease. Invasive pulmonary aspergillosis, occurring in immunocompromised patients, reflects the most serious disease with a high case-fatality rate. Patients with cystic fibrosis and severe asthma might develop allergic bronchopulmonary aspergillosis, while saphrophytic infections are observed in patients with lung cavities mainly due to tuberculosis. Histopathologically, a differentiation can be made into angio-invasive and airway invasive disease. If the host response is too weak or too strong, Aspergillus species are able to cause disease characterized either by damage from the fungus itself or through an exaggerated inflammatory response of the host, in both situations leading to overt disease associated with specific clinical signs and symptoms. The unraveling of the specific host - Aspergillus interaction has not been performed to a great extent and needs attention to improve the management of those clinical syndromes. PMID- 25135083 TI - Diagnostics in prosthetic joint infections. AB - Prosthetic joint infection (PJI) poses a significant burden on patients, clinicians and the healthcare economy. Although various tests have been established for the diagnosis of PJI, the diagnosis remains challenging. In this review, established and potential future diagnostic tests are presented, some of which could provide stepping stones towards improved diagnosis, identification of aetiological agents and efficacious therapeutic options for the management of PJI. PMID- 25135080 TI - Combination of BMP2 and MSCs significantly increases bone formation in the rat arterio-venous loop model. AB - INTRODUCTION: In this study the induction of bone formation in an axially vascularized bone matrix using mesenchymal stem cells (MSCs) and application of bone morphogenetic protein 2 (BMP2) was analyzed in the arteriovenous loop (AVL) model. MATERIALS AND METHODS: An AVL was created in the medial thigh of 42 rats and placed in a porous titanium chamber filled with a particulated porous hydroxyapatite and beta-tricalcium phosphate matrix and fibrin. In group A the fibrin was loaded with 5*10(6) DiI-stained fibrin gel-immobilized primary MSCs from syngenic Lewis rats, in group B the matrix was loaded with 60 MUg/mL BMP2 and in group C both, BMP2 and MSCs were applied at implantation time point. After 6 and 12 weeks, specimens were investigated by means of histological, morphometrical, and micro-computed tomography analysis. RESULTS: After implantation of an AVL a dense vascular network was visible in all groups. In group A, newly generated bone islands were detected in the periphery of the main vascular axis. Using BMP2 alone (group B), small islands of newly formed bone were visible evenly distributed in all parts of the constructs. In group C nearly the whole matrix was interspersed with bone formations. In all groups there was an increase of bone formation between the 6 and 12 weeks explantation time points. CONCLUSIONS: This study demonstrates for the first time the successful generation of axially vascularized bone substitutes using MSCs and BMP2 in the AVL rat model using a one step procedure. Using the combination of BMP2 and MSCs there was a significant increase of bone formations detectable compared to the BMP2 or MSCs alone groups. PMID- 25135081 TI - A program to identify prognostic and predictive gene signatures. AB - BACKGROUND: The advent of high-throughput technologies to profile human tumors has generated unprecedented insight into our molecular understanding of cancer. However, analysis of such high dimensional data is challenging and requires significant expertise which is not routinely available to many cancer researchers. RESULTS: To overcome this limitation, we developed a freely accessible and user friendly Program to Identify Molecular Signatures (PIMS). Importantly, such signatures allow important insight into cancer biology, as well as provide clinical tools to identify potential biomarkers that might provide means to accurately stratify patients into different risk or treatment groups. We evaluated the performance of PIMS by identifying and testing predictive and prognostic gene signatures for breast cancer, using multiple breast tumor microarray cohorts representing hundreds of patients. Importantly, PIMS identified signatures classified patients into high and low risk groups with at least similar performance to other commonly used gene signature selection techniques. CONCLUSIONS: Our program is contained entirely within a Microsoft Excel file and therefore requires no installation of any additional programs or training. Hence, PIMS provides an accessible tool for cancer researchers to identify predictive and prognostic gene signatures to advance their research. PMID- 25135084 TI - Molecular techniques for diagnosing prosthetic joint infections. AB - Prosthetic joint infections (PJI) can be broadly classed into two groups: those where there is a strong clinical suspicion of infection and those with clinical uncertainty, including 'aseptic loosening'. Confirmation of infection and identification of the causative organism along with provision of antibiotic susceptibility data are important stages in the management of PJI. Conventional microbiological culture and susceptibility testing is usually sufficient to provide this. However, it may fail due to prior antimicrobial treatment or the presence of unusual and fastidious organisms. Molecular techniques, in particular specific real-time and broad-range PCR, are available for diagnostic use in suspected PJI. In this review, we describe the techniques available, their current strengths, limitations and future development. Real-time pathogen specific and broad-range PCR (with single sequence determination) are suitable for use as part of the routine diagnostic algorithm for clinically suspected PJI. Further development of broad-range PCR with high-throughput (next-generation) sequencing is necessary to understand the microbiome of the prosthetic joint further before this technique can be used for routine diagnostics in clinically unsuspected PJI, including aseptic loosening. PMID- 25135085 TI - The clinical presentation of prosthetic joint infection. AB - Prosthetic joint infection (PJI) complicates ~1% of arthroplasties but accounts for considerable morbidity. Both the timing and features of PJI can vary widely. Patients may present with early (<=3 months post-operatively), delayed (3-24 months) or late disease (>24 months). They may be acutely unwell with systemic signs of sepsis or describe only a chronically painful joint with or without sinus formation. Diagnostic criteria as proposed by the Infectious Diseases Society of America and the Musculoskeletal Infection Society highlight the importance of joint sampling to obtain histological and robust microbiological evidence. Staphylococcus aureus and coagulase-negative staphylococci account for >50% of infections. Early infections are likely to have been acquired intra- or peri-operatively, whereas late infection is usually haematogenous in origin. Acute joint inflammation suggests the presence of intra-articular free-living bacteria, whereas chronic infections are associated with the formation of biofilm at the bone-cement or bone-prosthesis interface. The most significant risk factors predisposing to PJI are previous operation on the index joint, previous arthroplasty at a different site, American Society of Anesthesiologists' grade 2, 3 or 4, body mass index >25, malignancy and procedure duration <2 or >4 h. PMID- 25135086 TI - Clinical guidelines in the management of prosthetic joint infection. AB - Clinical practice guidelines for the diagnosis and management of prosthetic joint infection have been produced by a range of organizations. Guidelines stress the importance of multi-disciplinary working and of adopting a methodical approach. This includes careful assessment of the patient's surgical, medical and psychosocial problems, rational investigation, a decision-making framework for surgery and targeted, sometimes prolonged, use of intravenous or highly bioavailable oral antibiotics. Despite limited high-quality evidence, adoption of clinical guidelines can improve practice by reducing variation and by establishing conditions for the subsequent conduct of multicentre studies or systematic reviews. PMID- 25135087 TI - Prosthetic joint infection: managing infection in a bionic era. AB - There is increasing demand for prosthetic joint surgery and patients are becoming more challenging due to an ageing population often with comorbidities and immunosuppression. While prosthetic joint infection (PJI) rates are generally low, infection can be catastrophic for the patient and hence prevention of infection is critical. Infection, when it does occur, is further complicated by the global rise in antimicrobial resistance. This article introduces a series of papers on the epidemiology of PJI, its diagnosis, use of novel inflammatory markers and molecular techniques, clinical presentation, importance of biofilms, treatment guidelines and, finally, various strategies and novel antibiotic treatment regimens. PMID- 25135088 TI - Impact of bacterial biofilm on the treatment of prosthetic joint infections. AB - Microbial biofilm contributes to chronic infection and is involved in the pathogenesis of prosthetic joint infections. Biofilms are structurally complex and should be considered a dynamic system able to protect the bacteria from host defence mechanisms and from antibacterial agents. Despite the use of antibiotics recognized as effective against acute infections, prosthetic joint infections require long-term suppressive treatment acting on adherent bacteria. Conventional in vitro susceptibility testing methods are not suitable for biofilm-associated infections given that these tests do not take into account the physiological parameters of bacterial cells in vivo. Most anti-staphylococcal drugs are able to inhibit in vitro the adhesion of bacteria to a surface, considered to be the first step in biofilm formation. Recent studies suggest that the lack of activity of antibiotics against biofilm-embedded bacteria seems to be more related to the decreased effect of the drug on the pathogen than to the poor penetration of the drug into the biofilm. Eradication of biofilm-embedded bacteria is a very difficult task and combination therapy is required in the treatment of persistent infections involving biofilm. Although several combinations demonstrate potent efficacy, rifampicin is the most common partner drug of effective combinations against staphylococcal biofilms. Considering the complexity of biofilm-related infections, further studies are needed to assess the activity of new therapeutic agents in combination with antibiotics (quorum-sensing inhibitors, biofilm disruptors and specific anti-biofilm molecules). PMID- 25135089 TI - Current antibiotic management of prosthetic joint infections in Italy: the 'Udine strategy'. AB - The rate of prosthetic joint infections followed and cured at our institution is constantly increasing, in line with epidemiological data from the recent literature. This is probably related to the greater number of knee and hip prostheses implanted every year. For intermediate and late infections, only the two-stage approach is applied, as this demonstrates the best outcome in our experience. Particular attention is paid to microbiological isolation of the pathogen: multiple samples of tissue are collected during the interventions, and kept in culture for a longer period of time than usual. Sonication of prosthetic devices is used to enhance the sensitivity and specificity of the microbiological cultures. Histological examination influences surgical choices either towards implantation of a new prosthesis or replacement of the spacer. An empirical antibiotic backbone of a glycopeptide/lipopeptide and rifampicin is chosen, due to the leading role of Gram-positive bacteria in this setting and the high incidence of methicillin resistance in our centre (>30%), followed by an antibiotic regimen containing linezolid. If specific risk factors are present, an anti-Gram-negative drug is added to the regimen. Duration of therapy depends upon the approach that is chosen, usually being 6 weeks when the prosthesis is removed. Despite at the moment being limited by its small sample size, data from our experience confirms that our empirical approach may represent a valid choice during the early phase of treatment, by keeping linezolid for a step-down therapy of shorter duration (4 weeks). PMID- 25135090 TI - Clinical experience with linezolid for the treatment of orthopaedic implant infections. AB - Gram-positive cocci are commonly isolated in orthopaedic implant infections and their resistance to beta-lactams and fluoroquinolones is increasing. The high oral bioavailability of linezolid makes it an attractive oral alternative to glycopeptides and its use has increased in the last decade. To evaluate experience with linezolid in orthopaedic implant infections a systematic review of the literature available in English was undertaken. Only those articles describing series of >=10 patients with acute or chronic orthopaedic implant infections treated with linezolid and with a clear definition of diagnosis and outcome were selected. A total of 293 patients (79.9% had prosthetic joint infections) were analysed in the 10 articles included. The overall remission rate with at least 3 months of follow-up was 79.9%, depending on whether the implant was removed or not (94% versus 69.9%). The addition of rifampicin was described in only two articles and no significant difference was observed. Adverse events were frequent during prolonged administration of linezolid (34.3%), requiring treatment discontinuation in 12.8%. The most common event was anaemia (13.4%) followed by gastrointestinal symptoms (11.1%). In conclusion, linezolid seems a good oral treatment alternative for orthopaedic implant infections due to Gram positive cocci resistant to beta-lactams and fluoroquinolones. However, close monitoring of adverse events is required. PMID- 25135091 TI - Epidemiology and burden of prosthetic joint infections. AB - Whilst improvements in patient care have reduced the risk of infection in patients undergoing prosthetic joint surgery, the substantial and growing number of hip and knee arthroplasty procedures undertaken translates into a continued and potentially increasing burden on patients, healthcare providers and the wider economy. Increases in patient obesity will raise further challenges to prevention efforts given the associated elevated risk of infection. Ongoing monitoring of infection rates remains a critical means to identify and address local and national changes in the epidemiology of prosthetic joint infection and to assess the impact of interventions. PMID- 25135092 TI - Vitamin D: a new player in kidney transplantation? AB - Vitamin D is a hormone with pleiotropic effects. It mainly regulates calcium and phosphate metabolism through interactions with FGF23 and its receptor klotho. In addition, it has been shown that Vitamin D also regulates the immune response and has protective effects from cardiovascular disease, cancer and infections. Most renal transplant recipients have overt Vitamin D deficiency, a condition that may be associated with a decline in graft function and other complications. After kidney transplantation, elevated levels of FGF23 may predict increased risks of death and allograft loss. Theoretically, an optimal Vitamin D supplementation might favor operational tolerance and protect transplant recipients from the triad cardiovascular disease-cancer-infection. However, more solid data are needed to confirm this and to set the optimal level of serum Vitamin D supplementation in order to attain the best clinical outcome. PMID- 25135093 TI - Agriculture. PMID- 25135094 TI - Global travel. PMID- 25135096 TI - Identifying risk factors of musculoskeletal disorders on Korean farms. AB - BACKGROUND: Farming is known to pose musculoskeletal disorder risk factors, although how risk factors differ between farmers in various countries is largely unknown. OBJECTIVE: To identify ergonomic risk factors through a qualitative assessment of common tasks performed by South Korean farmers. METHODS: A convenience sample of Korean farmers was videotaped performing typical jobs on farms that produced rice, fruits and vegetables, or raised animals. Ergonomists identified poor ergonomic risk factors that may lead to musculoskeletal disorders including poor postures of the shoulders, wrists, neck, low back, and knees. RESULTS: Severe flexion and lifting of heavy loads was common across farms. While many of the concerning risk factors identified were similar to those in other parts of the world, one was unique in this population - deep knee flexion while weeding, harvesting, and sorting. CONCLUSIONS: Given the Korean farm population is aging at an alarming rate and remains dominated by small farms, many of these potential risk factors may have a continued or increased role in the development of musculoskeletal disorders. While the current study provided the first observational assessment of ergonomic demands on Korean farms, more quantitative and rigorous investigations are needed to establish actual risk factors. PMID- 25135097 TI - A randomized intervention trial to reduce mechanical exposures in the Colombian flower industry. AB - BACKGROUND: Evidence on effectiveness of ergonomic interventions to reduce mechanical demands of the upper extremity is scarce in agriculture. OBJECTIVE: To conduct an ergonomic intervention to reduce mechanical exposures on workers during manual flower cutting, while emphasizing postural education and reduction of force requirements. PARTICIPANTS: Seventy seven workers (20 to 55 years old; 80% women) from six companies that cultivate roses participated in this study. METHODS: Participants from three companies were randomly assigned to control and intervention groups. A postural education program and a maintenance program was designed and implemented in the intervention group aiming to achieve more neutral postures of the wrist and forearm and to reduce force requirements during rose cutting. Changes in self-reported effort and upper extremity postures, kinematics and muscular activity between baseline and follow-up assessments were evaluated. RESULTS: Most of the observed changes in the evaluated mechanical exposures were moderate for both groups. The intervention group showed differential improvements compared to the control group for 95th percentile forearm pronation (intervention group went from 50.6 to 35.6 degrees ; control group went from 18.4 to 34.7 degrees ); and to some degree for the maximum wrist radial deviation (the intervention group went from 17 degrees to 7.6 degrees ; control group went from 10.1 degrees to 7.8 degrees ). Also, the mean elbow flexion for the control group was reduced from 62.3 to 48.4 degrees , whereas it increased from 52.2 to 57.3 degrees in the intervention group. No differential changes between the intervention and control groups were observed for the kinematic variables, except for an unexpected reduction in the 95th percentile velocity of wrist flexion extension in the control group, which was not observed in the intervention group. Lastly, although observed changes in muscular activity were not statistically significant, improvements were observed for the intervention group for the flexor and extensor carpi radialis and the flexor carpi ulnaris; although the opposite was true for the extensor carpi ulnaris. CONCLUSIONS: Important although sometimes mixed results were achieved with this field intervention, focusing on postural and force requirement demands. The positive results are encouraging considering the presence of typical limitations observed in field intervention studies. PMID- 25135099 TI - Better understanding of bariatric surgery outcomes through sleep. PMID- 25135100 TI - Is systemic inflammation not involved in endoscopic duodenal-jejunal bypass liner induced diabetes remission? PMID- 25135101 TI - Validating a new computed tomography atlas for grading ankle osteoarthritis. AB - As the most common joint disease, osteoarthritis (OA) poses a significant source of pain and disability. It can be defined by classic radiographic findings, particular symptoms, or a combination of the 2. Although specific grading scales have been developed to evaluate OA in various joints, such as the shoulder, hip, and knee, no definitive classification system is available for grading OA in the ankle. The purpose of the present study was to create and validate a standardized atlas for grading (or staging) ankle osteoarthritis using computed tomography (CT) and "hallmark" findings noted on coronal, sagittal, and axial views extrapolated from the Kellgren-Lawrence radiographic scale. The CT scans of 226 patients at the Miami Veterans Affairs Medical Center were reviewed. An atlas was derived from a retrospective review of 30 remaining CT scans taken from July 2008 to November 2011. After this review, 3 orthogonal static CT images, obtained from 11 remaining patients, were chosen to represent the various stages on the OA scale and were used to test the validity of the atlas developed by 2 of us (M.M.C. and N.D.V.). A multispecialty panel of 9 examiners, excluding ourselves, independently rated the 11 CT scan subjects. The differences among examiners and specialties were calculated, including an intra-examiner agreement for 2 separate readings spaced 9 months apart. Although the small number of subspecialty examiners made the intraspecialty comparisons difficult to validate, the findings nevertheless indicated excellent agreement among all specialty groups, with good intra-investigational (intraclass correlation coefficient 0.962 and 1) inter investigational (intraclass correlation coefficient 0.851) values. These results appeared to validate the CT ankle OA atlas, which we believe will be a valuable clinical and research tool, one that will likely be more beneficial than less relevant generalized OA grading scales in use today. PMID- 25135102 TI - A large-scale study on epidemiology and risk factors for chronic ankle instability in young adults. AB - Up to 40% of ankle sprains can result in chronic ankle instability (CAI). The prevalence of CAI and its association with body mass index (BMI) and height in the general young adult population has not been reported. The database records of young adults before recruitment into mandatory military service were studied. Information on the disability codes associated with CAI was retrieved. Logistic regression models were used to assess the association between the BMI and body height with various grades of CAI severity. The study cohort included 829,791 subjects (470,125 males and 359,666 females). The prevalence was 0.7% for mild CAI and 0.4% for severe instability in males and 0.3% and 0.4%, respectively, for females (p < .001). An increased BMI was associated with ankle instability in males (overweight, odds ratio [OR] 1.249, p < .001; obese, OR 1.418, p < .001) and females (overweight, OR 1.989 p < .001; obese, OR 2.754, p < .001). The body height was associated with an increased risk of CAI when the highest height quintile was compared with the lowest height quintile in both males (OR 2.443, p < .001) and females (OR 1.436, p < .001) for all levels of instability severity. The present study has shown a greater prevalence of CAI among males than females in a general healthy young adult population. CAI was associated with an increased BMI and greater body height for all grades of instability severity. PMID- 25135103 TI - Treatment of an open medial tibiotalar dislocation with no associated fracture. AB - Tibiotalar dislocations without associated fractures are very uncommon in adults, and only a few studies have been published regarding this injury. More than 50% of these dislocations will be posteromedial, with a high incidence of open injuries, and 25% are pure posterior dislocations. In the present report, we discuss our experience and management of a medial tibiotalar dislocation with no associated fracture. In the present case, the patient was brought to the operating room on presentation to our facility and underwent irrigation and debridement with primary closure of his wound. He was immobilized postoperatively. The patient tolerated the operation well and did not sustain any postoperative complications. He was able to regain function of the injured extremity until he was lost to follow-up. Regarding treatment, the surgery should be speedy, gentle to the soft tissue, and with as little implanted material as possible. Although we do not advocate that our management and treatment of this injury become the standard, the present case provides a good example of some of the challenges often encountered when treating these injuries. PMID- 25135104 TI - Pedal Gangrenous Changes in the Digits of an Adolescent With Ulcerative Colitis: A Case Report. AB - Ulcerative colitis is an autoimmune inflammatory disease of the colon and is occasionally associated with thrombosis. We report the case of an adolescent with ulcerative colitis who presented with bilateral gangrenous toes without signs of ascending cellulitis. Radiographs indicated the presence of bilateral and erosive changes in the distal phalanges. The vascular team referred the patient for podiatric intervention for distal vasculitis and thrombosis of the digital vessels. Transphalangeal amputations were performed, and postoperative antibiotics were initiated. The surgical sites healed uneventfully, and the patient was able to resume daily activities. Thrombosis of the foot in the context of ulcerative colitis is a rare, but serious, complication that can lead to serious comorbidities, including amputation. PMID- 25135105 TI - Isolated Fifth Metatarsocuboid Coalition: A Case Report. AB - Isolated tarsometatarsal coalitions are extremely rare, and the previous 5 documented cases involved the first and third metatarsocuneiform joints. We report the case of a 69-year-old female with symptomatic fifth metatarsocuboid coalition associated with ipsilateral varus-type ankle osteoarthritis and instability. The patient was successfully treated by arthrodesis of the fifth metatarsocuboid joint, resection of the hypertrophied tuberosity of the fifth metatarsal, advancement of the peroneus brevis tendon, opening wedge distal tibial osteotomy, and calcaneal displacement osteotomy. After 1 year, 6 months, she was able to walk well, although she complained of minor discomfort under the fifth metatarsal base, which resolved with the use of protective padding. Radiographs at this stage confirmed consolidation of both the arthrodesis and the osteotomy sites. Although isolated fifth metatarsocuboid coalition is less likely to be encountered than other tarsal coalitions, it can sometimes be painful enough to necessitate surgery. PMID- 25135106 TI - Holocene variations in peatland methane cycling associated with the Asian summer monsoon system. AB - Atmospheric methane concentrations decreased during the early to middle Holocene; however, the governing mechanisms remain controversial. Although it has been suggested that the mid-Holocene minimum methane emissions are associated with hydrological change, direct evidence is lacking. Here we report a new independent approach, linking hydrological change in peat sediments from the Tibetan Plateau to changes in archaeal diether concentrations and diploptene delta(13)C values as tracers for methanogenesis and methanotrophy, respectively. A minimum in inferred methanogenesis occurred during the mid-Holocene, which, locally, corresponds with the driest conditions of the Holocene, reflecting a minimum in Asian monsoon precipitation. The close coupling between precipitation and methanogenesis is validated by climate simulations, which also suggest a regionally widespread impact. Importantly, the minimum in methanogenesis is associated with a maximum in methanotrophy. Therefore, methane emissions in the Tibetan Plateau region were apparently lower during the mid-Holocene and partially controlled by interactions of large-scale atmospheric circulation. PMID- 25135107 TI - Bilateral lens luxation and intracapsular lens extractions in a Matshchie's tree kangaroo. AB - An adult, female, captive, Matshchie's tree kangaroo was diagnosed with an anterior lens luxation in the right eye and a lens subluxation in the left eye. Both eyes were treated surgically with intracapsular lens extractions. A 360 degrees rhegmatogenous retinal detachment was diagnosed 6 months postoperatively in the left eye. Aphakic vision was maintained in the right eye 9 months postoperatively. Based on family history and the lack of antecedent ocular disease, the lens luxations were presumed to be inherited and veterinarians should be aware of this condition within the captive tree kangaroo population. PMID- 25135108 TI - Giant seborrheic keratoses on penis. AB - INTRODUCTION: Seborrheic keratoses are very common benign epidermal tumors. Despite the high frequency, the pathogenesis is still unknown. They are extremely rare in the genital area. The participation of human papilloma viruses (HPVs) in pathogenesis of seborrheic keratoses is being discussed. AIMS: The aims of this case report are to inform about extremely rare lesion in genital area in a young man and evaluate the association of HPVs in the development of seborrheic keratoses. METHODS: We used histopathological examination to establish the correct diagnosis, which revealed signs of seborrheic keratosis. The real-time polymerase chain reaction method confirmed low-risk HPV 6 from the lesions. MAIN OUTCOME MEASURES: HPVs may play a role in pathogenesis of seborrheic keratoses. RESULTS: The patient was successfully treated with shave excision under spinal anesthesia. Six-month follow-up was without any recurrence. We suggest that HPVs can be considered as etiologic factor in creation of seborrheic keratosis. CONCLUSIONS: Seborrheic keratoses are very common on sun-exposed skin, but they are rare in the genital area, such as on the shaft of penis. This localization may lead to misdiagnosis. Seborrheic keratoses in genital area might negatively influence the sexual life of the patient. Containing HPV 6 low-risk virus, they never lead to malignant transformation. PMID- 25135109 TI - Regulating drug release from pH- and temperature-responsive electrospun CTS-g PNIPAAm/poly(ethylene oxide) hydrogel nanofibers. AB - Temperature- and pH-responsive polymers have been widely investigated as smart drug release systems. However, dual-sensitive polymers in the form of nanofibers, which is advantageous in achieving rapid transfer of stimulus to the smart polymeric structures for regulating drug release behavior, have rarely been explored. In this study, chitosan-graft-poly(N-isopropylacrylamide) (CTS-g PNIPAAm) copolymer was synthesized by using 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide (EDC) and N-hydroxy succinimide (NHS) as grafting agents to graft carboxyl-terminated PNIPAAm (PNIPAAm-COOH) chains onto the CTS biomacromolecules, and then CTS-g-PNIPAAm with or without bovine serum albumin (BSA) was fabricated into nanofibers through electrospinning using poly(ethylene oxide) (PEO, 10 wt%) as a fiber-forming facilitating additive. The BSA laden CTS-g-PNIPAAm/PEO hydrogel nanofibers were tested to determine their drug release profiles by varying pH and temperature. Finally, cytotoxicity of the CTS-g-PNIPAAm/PEO hydrogel nanofibers was evaluated by assaying the L929 cell proliferation using the MTT method. It was found that the synthesized CTS-g PNIPAAm possessed a temperature-induced phase transition and lower critical solution temperature (LCST) at 32 degrees C in aqueous solutions. The rate of BSA release could be well modulated by altering the environmental pH and temperature of the hydrogel nanofibers. The CTS-g-PNIPAAm/PEO hydrogel nanofibers supported L929 cell growth, indicative of appropriate cytocompatibility. Our current work could pave the way towards developing multi-stimuli responsive nanofibrous smart materials for potential applications in the fields of drug delivery and tissue engineering. PMID- 25135110 TI - Effects of bisoprolol and losartan treatment in the hypertrophic and failing right heart. AB - BACKGROUND: Sympathetic adrenergic stimulation and the renin-angiotensin aldosterone system are highly elevated in right heart failure. We evaluated if treatment with the adrenergic receptor blocker bisoprolol or the angiotensin II receptor blocker losartan could prevent the progression of right ventricular (RV) hypertrophy and failure in rats after pulmonary trunk banding (PTB). METHODS AND RESULTS: Male Wistar rats were randomized to severe PTB with a 0.5-mm banding clip (PTB0.5, n = 29), moderate PTB with a 0.6-mm banding clip (PTB0.6, n = 28), or sham operation (SHAM, n = 13). The PTB0.5 and PTB0.6 rats were randomized to 6 weeks of 10 mg/kg/d bisoprolol treatment, 20 mg/kg/d losartan treatment, or vehicle treatment. The PTB caused hypertrophy, dilation, and reduced function of the RV in all rats subjected to the procedure. Rats subjected to the more severe banding developed decompensated RV failure with extracardiac manifestations. Treatment with bisoprolol slowed the heart rate, and treatment with losartan lowered mean arterial pressure, confirming adequate dosing, but none of the treatments improved RV function or arrested the progression of RV hypertrophy and failure compared with vehicle. CONCLUSIONS: In our PTB model of pressure overload induced RV hypertrophy and failure, treatment with bisoprolol and losartan did not demonstrate any beneficial effects in compensated or decompensated RV failure. PMID- 25135111 TI - NF-kappaB repressing factor downregulates basal expression and mycobacterium tuberculosis induced IP-10 and IL-8 synthesis via interference with NF-kappaB in monocytes. AB - BACKGROUND: Our previous study showed NF-kappaB repressing factor (NKRF) downregulates IP-10 and IL-8 synthesis in the peripheral blood mononuclear cells and alveolar macrophages of TB patients with high bacterial loads. However, the mechanism underlying the repressive effect of NKRF is not fully understood. RESULTS: The levels of IP-10, IL-8 and NKRF were significantly up-regulated in THP-1 cells treated with heated mycobacterium tuberculosis (H. TB). NKRF inhibited NF-kappaB-mediated IP-10 and IL-8 synthesis and release induced by H. TB. The repressive effect of NKRF is mediated via interference with NF-kappaB (p65) binding and RNA polymerase II recruitment to promoter sites of IP-10 and IL 8. CONCLUSIONS: We have elucidated that direct contact with MTb induces IP-10, IL 8 and a concomitant increase in NKRF in THP-1 cells. The up-regulated NKRF serves as an endogenous repressor for IP-10 and IL-8 synthesis to hinder host from robust response to MTb infection. PMID- 25135112 TI - Assessment of type 2 diabetes risk conferred by SNPs rs2241766 and rs1501299 in the ADIPOQ gene, a case/control study combined with meta-analyses. AB - We conducted a case/control study to assess the impact of two SNPs, rs2241766 and rs1501299 within the ADIPOQ gene, on type 2 diabetes (T2D) susceptibility in a Chinese Han dataset (741 cases and 902 controls). SNP rs2241766 was found significantly associated with T2D risk in the additive model, dominant model and recessive model. A marginal association was detected for SNP rs1501299 in the additive model and recessive model after Bonferroni correction, and haplotype analysis provided additional evidence supporting the association between these two SNPs and T2D risk. A meta-analysis including 29 published datasets along with current dataset was next carried out to further confirm the association. In consistent with our case/control results, rs2241766 showed a significant association with T2D in the dominant model and additive model, and the association between rs1501299 and T2D was also characterized in the homozygote model, dominant model, recessive model, and additive model. Of note, the association became much stronger in East Asians after exclusion of ethnic stratification. Together, our data support that the rs2241766 and rs1501299 polymorphisms within the ADIPOQ gene confer genetic susceptibility for type 2 diabetes, especially in the Chinese Han population. PMID- 25135114 TI - Munchausen syndrome: multiple episodes of polymicrobial bacteremia. PMID- 25135113 TI - Optical mapping of optogenetically shaped cardiac action potentials. AB - Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation. PMID- 25135115 TI - Serotonergic systems are implicated in antinociceptive effect of m trifluoromethyl diphenyl diselenide in the mouse glutamate test. AB - The organoselenium compound m-trifluoromethyl diphenyl diselenide (m-CF3-PhSe)2 has antinociceptive actions in several animal models, which are mediated by interaction with endogenous opioid systems. It also shows antidepressant-like action mediated by both opioid and serotonergic systems. Considering that serotonin (5-HT) plays an important role in the descending control of pain, this study further investigated the role of serotonergic systems in the antinociceptive action of (m-CF3-PhSe)2 in the glutamate-induced licking behavior model in mice. (m-CF3-PhSe)2 (1-50 mg/kg, p.o.), morphine (2.5 mg/kg, s.c.) or paroxetine (5 mg/kg, i.p.) reduced glutamate-induced nociception. Selective 5 HT1A and 5-HT2A receptor antagonists, WAY100635 (0.7 mg/kg, i.p.) and ketanserin (0.3 mg/kg, i.p.), but not the selective 5-HT3 receptor antagonist, ondansetron (0.5 mg/kg, i.p.), prevented the antinociceptive effect of (m-CF3-PhSe)2 (10 mg/kg) in the glutamate test. In biochemical studies, (m-CF3-PhSe)2 (10 and 50 mg/kg) decreased [(3)H]5-HT uptake in crude synaptosomes of mouse brains and slightly inhibited in vitro [(3)H]5-HT binding. In kinetic studies, the selenium (Se) distribution was determined at different time points after the administration of (m-CF3-PhSe)2 (500 mg/kg, p.o.) to mice. After 30 min, a high amount of Se was found in liver and kidneys, followed by the lung, red blood cells, serum and brain. A significant amount of Se accumulated in fat over the course of 8h. Urine was an important route of Se excretion originating from (m CF3-PhSe)2. Collectively, results of this study indicate an involvement of the serotonergic systems in the antinociceptive effect of (m-CF3-PhSe)2 and a wide distribution of Se derived from this compound. PMID- 25135117 TI - Interventional cardiology: SORTing OUT stents--everolimus limits very late stent thrombosis. PMID- 25135116 TI - Plant disease resistance is augmented in uzu barley lines modified in the brassinosteroid receptor BRI1. AB - BACKGROUND: Brassinosteroid hormones regulate many aspects of plant growth and development. The membrane receptor BRI1 is a central player in the brassinosteroid signaling cascade. Semi-dwarf 'uzu' barley carries a mutation in a conserved domain of the kinase tail of BRI1 and this mutant allele is recognised for its positive contribution to both yield and lodging resistance. RESULTS: Here we show that uzu barley exhibits enhanced resistance to a range of pathogens. It was due to a combination of preformed, inducible and constitutive defence responses, as determined by a combination of transcriptomic and biochemical studies. Gene expression studies were used to determine that the uzu derivatives are attenuated in downstream brassinosteroid signaling. The reduction of BRI1 RNA levels via virus-induced gene silencing compromised uzu disease resistance. CONCLUSIONS: The pathogen resistance of uzu derivatives may be due to pleiotropic effects of BRI1 or the cascade effects of their repressed BR signaling. PMID- 25135118 TI - Coronary artery disease: Cost-effectiveness of CABG surgery versus PCI in complex CAD. PMID- 25135119 TI - Diabetes: Effects of strict glycaemic control on ischaemic heart disease. PMID- 25135121 TI - Treatment patterns and their outcomes of acute aortic intramural hematoma in real world: multicenter registry for aortic intramural hematoma. AB - BACKGROUND: Intramural hematoma of the aorta (IMH), a variant of classic aortic dissection, shows very dynamic process in the early phase. The aim of this study is to evaluate clinical outcomes of patients with acute aortic IMH from real world registry data. METHODS: We analyzed 165 consecutive patients with acute IMH from five medical centers in Korea. All patients were divided into two groups; type A (n = 61, 37.0%) and type B (n = 104, 63.0%) according to the Stanford classification. Clinical outcomes and morphological evolution by CT were analyzed for 2 years. RESULTS: Most of the patients (77.0% of type A and 99.0% of type B, P < 0.001) were treated medically during their initial hospitalization. There were no significant differences in in-hospital mortality (4.9% vs. 2.9%, P = 0.671) and 2-year mortality (13.1% vs. 11.5%, P = 0.765) between two groups. During the 2-year follow up period, progression to aortic dissection (18.0% vs. 6.7%, P = 0.037) and surgical treatment (29.5% vs. 2.9%, P < 0.001) were higher in type A. For the type A patients, there were no significant difference in in hospital mortality (7.1% of surgery vs. 4.3% of medical, P = 0.428) and 2-year mortality (7.1% of surgery vs. 14.9% of medical, P = 0.450) in terms of initial treatment strategy. CONCLUSION: For real world practice in Korea, most of IMH patients were treated medically at presentation and showed favorable outcomes. Thus, even in type A acute IMH, early medical treatment with alternative surgical conversion for selected, complicated cases would be a favorable treatment option. PMID- 25135122 TI - Obesity delays functional recovery in trauma patients. AB - BACKGROUND: Obesity is known to complicate trauma hospital stays. We hypothesize that obesity delays functional recovery in trauma patients. MATERIALS AND METHODS: Between 2005 and 2007, adult patients with a hospital length of stay >24 h were prospectively recruited for the study. Functional Independence Measurement (FIM) scores were calculated at the time of admission, discharge, and 6 mo after discharge. Patients were classified as nonobese (body mass index [BMI] <25), overweight (BMI >=25 and <30), obese (BMI >=30 and <35), and morbidly obese (BMI >=35). Multivariate analyses were performed to determine the impact of obesity on FIM scores. RESULTS: Two hundred thirty-five patients met the study inclusion criteria. Average injury severity scores was >18. We recorded no mortality at the time of discharge and follow-up. During acute hospital stay stage, nonobese patients had an average of 24 points increase on FIM scores compared with morbidly obese patients with 16 points improvement (P = 0.023). Compared with nonobese patients, the rate of recovery was reduced by 30% in overweight (P = 0.034), 37% in obese (P = 0.025), and 48% in morbidly obese patients (P = 0.003). Alternatively, we found that for every unit increase in BMI, the functional recovery rate was reduced by 4% (P < 0.001). Changes in FIM scores during the postdischarge period were not significantly different by obesity classification, and all groups achieve similar functional outcome at follow-up (P = 0.482). CONCLUSIONS: Most trauma patients achieve full functional recovery some time after hospital discharge, but the recovery is delayed in obese patients and the delay is directly correlated with the severity of obesity. PMID- 25135120 TI - Clinicopathological characteristics of oral squamous cell carcinoma in Northern Norway: a retrospective study. AB - BACKGROUND: The main aim of the study was to evaluate if patients with oral squamous carcinomas in Northern Norway differ from patients in other countries with regard to clinicopathological characteristics and also study the influence of risk factors. Such a comparison is of demographical interest, and also important for the interpretation of result from studies on prognostic biomarkers. METHODS: We describe clinicopathological characteristics of 133 North Norwegian patients diagnosed with squamous cell carcinoma of the oral cavity in the period 1986-2002, and evaluate the significance of different risk factors. RESULTS: The cohort consisted of 69 men and 64 women, giving male/female ratio of 1.1. Forty seven of the 133 patients (35%) died of the disease within 5 years from diagnosis. There was no significant difference between the genders concerning time to disease specific death, even though men both smoked and drank more alcohol than women. As expected, the strongest predictors for disease specific death were tumour size and the presence of regional lymph node metastasis. We also found that heavy smokers and drinkers presented with more advanced disease, more often localized to the floor of mouth compared to non-smoking and abstinent patients, who more often presented with tumours of the mobile tongue. CONCLUSIONS: Our results correlate well with previously published clinicopathological data on comparable cohorts, which is important when considering the applicability of results from biomarker studies performed on this material compared to other cohorts, and vice versa. PMID- 25135123 TI - Metformin improves skin flap survival through nitric oxide system. AB - BACKGROUND: Metformin has shown cardioprotective effects in experimental models of ischemia reperfusion, which is partially mediated through nitric oxide (NO) synthesis. We investigated the effects of metformin pretreatment in a rat model of random-pattern skin flap, and the probable role of NO system. MATERIALS AND METHODS: In the first experiment, the rats received increasing doses of metformin (150, 200, and 300 mg/kg), 4 h before the procedure. Dorsal skin flaps with caudal pedicles were elevated at the midline and flap survival was measured 7 d after surgery. Pathologic review of the skin flap specimen was performed in a subset of animals. In the second experiment, for evaluation of the role of NO, an NO synthase inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME) was administered with and without the effective dose of metformin. In the next experiment, subtherapeutic dose of NO precursor, L-Arginine, was administered with and without subeffective dose of metformin. RESULTS: Metformin pretreatment at doses of 200 and 300 mg/kg significantly increased skin flap survival rate. However, administration of L-NAME abolished the protective effects of metformin. On the other hand, subtherapeutic dose of L-arginine augmented the effects of low dose metformin and significantly increased skin flap survival. Skin flaps from those rats that received 300 mg/kg metformin pretreatment and those treated with subtherapeutic doses of L-arginine and metformin showed increased vasodilation compared with control group. CONCLUSIONS: Metformin pretreatment can improve skin flap survival through an NO dependent pathway. PMID- 25135126 TI - Electrocardiographic screening should not be implemented for children and adolescents between ages 1 and 19 in the United States. PMID- 25135125 TI - Electrocardiographic screening of all infants, children, and teenagers should be performed. PMID- 25135124 TI - Impact of oral melatonin on critically ill adult patients with ICU sleep deprivation: study protocol for a randomized controlled trial. AB - BACKGROUND: Sleep deprivation is common in critically ill patients in intensive care units (ICU). It can result in delirium, difficulty weaning, repeated nosocomial infections, prolonged ICU length of stay and increased ICU mortality. Melatonin, a physiological sleep regulator, is well known to benefit sleep quality in certain people, but evidence for the effectiveness in ICU sleep disturbance is limited. METHODS/DESIGN: This study has a prospective, randomized, double-blind, controlled, parallel-group design. Eligible patients are randomly assigned to one of the two treatment study groups, labelled the 'melatonin group' or the 'placebo group'. A dose of 3 mg of oral melatonin or placebo is administered at 9:00 pm on four consecutive days. Earplugs and eye masks are made available to every participant. We plan to enrol 198 patients. The primary outcome is the objective sleep quality measured by the 24-hour polysomnography. The secondary outcomes are the subjective sleep quality assessed by the Richards Campbell Sleep Questionnaire, the anxiety level evaluated by the Visual Analogue Scale-Anxiety, the number of delirium-free days in 8 and 28 days, the number of ventilation-free days in 28 days, the number of antibiotic-free days, ICU length of stay, the overall ICU mortality in 28 days and the incidence and severity of the side effects of melatonin in ICU patients. Additionally, the body stress levels, oxidative stress levels and inflammation levels are obtained via measuring the plasma melatonin, cortisone, norepinephrine, malonaldehyde(MDA), superoxide dismutase(SOD), interleukin-6 (IL-6) and interleukin-8 (IL 8)concentrations. DISCUSSION: The proposed study will be the first randomized controlled study to use the polysomnography, which is the gold standard of assessing sleep quality, to evaluate the effect of melatonin on the sleep quality and circadian rhythms of ICU patients. The results may recommend a new treatment for ICU patients with sleep deprivation that is safe, effective and easily implementable in daily practice. TRIAL REGISTRATION: This study was registered with ClinicalTrials (NCT; registration number: ChiCTR-TRC-14004319) on 4 March 2013. PMID- 25135127 TI - Cardiovascular implications in preeclampsia: an overview. PMID- 25135130 TI - Demonstration of inverted left atrial appendage using cardiac computed tomography: an unusual complication mimicking left atrial mass after cardiac surgery. PMID- 25135129 TI - Impact of septal radiofrequency ventricular tachycardia ablation: insights from magnetic resonance imaging. PMID- 25135131 TI - Cerebral and sinus vein thrombosis. PMID- 25135132 TI - Letter by Li and Yu regarding article, "ten-eleven translocation-2 (TET2) is a master regulator of smooth muscle cell plasticity". PMID- 25135133 TI - Response to letter regarding article, "ten-eleven translocation-2 (TET2) is a master regulator of smooth muscle cell plasticity". PMID- 25135134 TI - Letter by Zhang regarding article, "early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis". PMID- 25135135 TI - Response to letter regarding article, "early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack: an updated systematic review and meta-analysis". PMID- 25135137 TI - [Occurrence of Shiga toxigenic Escherichia coli strains in pigs and cattle at slaughterhouses in the Czech Republic in 2013]. AB - OBJECTIVES: This study was performed in cooperation with the State Veterinary Administration (SVA) in order to monitor the occurrence of Shiga toxin-producing Escherichia coli isolates in swabs from the carcasses of pigs and cattle at slaughterhouses. MATERIAL AND METHODS: From June to August 2013, SVA staff took 168 swabs from cattle and 318 from pigs at 157 different slaughters in the Czech Republic. Basic processing of the samples was carried out in the State Veterinary Institutes (SVIs) in Prague, Jihlava and Olomouc according to the methodical process coordinated by the National reference laboratory (NRL) for Escherichia coli (Czech Ministry of Agriculture). The procedure was based on the guideline ISO TS 13136. RESULTS: Out of the 486 swabs, twenty-two positive samples were detected. There were a total of 22 isolates of Shiga toxigenic E. coli (STEC) and 1 strain with the characteristic of enterohemorrhagic E. coli (EHEC). Genes typical for enteroaggregative E. coli (EAggEC) were not found in any of the isolates. Most STEC strains originated from pigs. The stx1 gene was detected twice (stx1a, stx1d) and the stx2 gene 13 times (12 times stx2e, once stx2a). Seven STEC isolates were detected from samples of cattle origin. One strain was stx1 (stx1a) -positive, the stx2 gene was found 6 times (4 stx2e, 1 stx2a and 1 stx2c). One isolate carried simultaneously both stx1a and stx2a. Each of the serogroups O91, O113 and O146 described as etiological agents of severe disease in humans were detected only once. None of these strains harbored additional virulence factors typical for strains causing serious illness. CONCLUSION: RESULTS of this study show the overall prevalence of Shiga toxigenic E. coli of 4.5 % and 0.2 % of enterohemorrhagic strains in the studied samples. Raw meat originating from local farms does not currently represent an important source of STEC for humans. PMID- 25135138 TI - [Familial occurrence of botulism - a case report]. AB - Botulism, a life-threatening condition, is very rare in the Czech Republic. Since 1960, a total of 155 cases have been reported; between 2010 and 2012, not a single case was identified. This is a case report of familiar occurrence of botulism following consumption of home-made pork and liver pate in three family members admitted to the Department of Infectious, Tropical and Parasitic Diseases, Na Bulovce Hospital in Prague in May 2013. The neurological symptoms were dominated by diplopia and dysarthria. After administration of an antitoxin, all patients recovered. Given the poor availability of the antitoxin, a decision was made following this small family epidemic to have an emergency reserve of life-saving anti-infective drugs for the Czech Republic in the Toxicological Information Center in Prague. PMID- 25135139 TI - [Emergency reserve of life-saving anti-infective drugs]. AB - OBJECTIVES: Problems with importing non-registered medicines for treating rare life-threatening infectious diseases led to establishment of the Emergency Anti Infective Drug Reserve (EAIDR) for the Czech Republic. METHODS: Thirteen anti infective drugs are included in the project: antisera against rabies virus, varicella-zoster virus, and botulinum toxin; antituberculosis drugs (intravenous rifampicin and isoniazid; capreomycin, cycloserine, and clofazimine); antiparasitics (intravenous quinine, primaquine, meglumine antimoniate, and praziquantel); and pentamidine. These drugs are imported according to the Czech drug legislation (specific drug availability programs). Realization: The project, approved by the Czech Ministry of Health in September 2013, was started in January 2014. The anti-infective drugs sufficient for 2-4 patients are permanently available in the Toxicological Information Center (TIC) in Prague. The medicines can be applied in any hospital throughout the Czech Republic within several hours. CONCLUSIONS: All but three drugs are available at present; the remaining ones will be imported after new batches of these drugs are released. PMID- 25135140 TI - [Campylobacteriosis]. AB - Campylobacteriosis belongs to the most frequent bacterial gastrointestinal infections worldwide. In the past several years, an increasing trend in the prevalence of campylobacteriosis has been observed in many countries. The rapid spread of antibiotic resistance in Campylobacter spp. also poses a major challenge. The authors review current knowledge on the microbiology of Campylobacter spp., complex pathogenetic as well as pathophysiological mechanisms in the development and course of campylobacteriosis and related complications such as Guillain-Barre syndrome. PMID- 25135141 TI - [Diagnosis and therapy of Clostridium difficile infection: Czech national guidelines]. AB - Clostridium difficile infection (CDI) is a disease of varying severity. Its manifestations range from mild diarrhea to life-threatening paralytic ileus, painful distension of the large bowel, and sepsis. Another possible manifestation of the disease is recurring colitis that can exhaust the patient. For establishing the diagnosis, the patient's stool should be examined with two or three different microbiological methods (testing for clostridial toxins A and B; testing for clostridial glutamate dehydrogenase, anaerobic culture with specific media, or PCR detection of genes for production of clostridial toxins). An alternative way of assessing the etiology is colonoscopic examination; the disease is confirmed if characteristic patchy pseudomembranes are present in the bowel mucosa. Optimal treatment depends on severity of the disease and on the risk of recurrence. Metronidazole, vancomycin and fidaxomicin are used as basic drugs. Fecal transplantation is effective in recurrent disease. In the hospital setting, patients suffering from CDI should be isolated for the entire duration of diarrhea. Surveillance rules also should be applied, together with early treatment of symptomatic patients and prevention of the spread of the infection. Higher incidence of CDI in a ward implies that the local antibiotic prescription habits should be revised. PMID- 25135142 TI - Response to: laboratory assessment may be dependent on the time of liver biopsy. PMID- 25135144 TI - [Critical care medicine and transplantation medicine: A task for each intensive care unit]. PMID- 25135143 TI - Exploration of shared decision-making processes among dieticians and patients during a consultation for the nutritional treatment of dyslipidaemia. AB - BACKGROUND: Shared decision making (SDM) holds great potential for improving the therapeutic efficiency and quality of nutritional treatment of dyslipidaemia by promoting patient involvement in decision making. Adoption of specific behaviours fostering SDM during consultations has yet to be studied in routine dietetic practice. OBJECTIVE: Using a cross-sectional study design, we aimed to explore both dieticians' and patients' adoption of SDM behaviours in dietetic consultations regarding the nutritional treatment of dyslipidaemia. METHODS: Twenty-six dieticians working in local health clinics in the Quebec City metropolitan area were each asked to identify one dyslipidaemic patient they would see in an upcoming consultation. Based on the Theory of Planned Behaviour (TPB), questionnaires were designed to study two targeted SDM behaviours: 'to discuss nutritional treatment options for dyslipidaemia' and 'to discuss patients' values and preferences about nutritional treatment options for dyslipidaemia'. These questionnaires were administered to the dietician-patient dyad individually before the consultation. Associations between TPB constructs (attitude, subjective norm and perceived behavioural control) towards behavioural intentions were analysed using Spearman's partial correlations. RESULTS: Thirteen unique patient-dietician dyads completed the study. Perceived behavioural control was the only TPB construct significantly associated with both dieticians' and patients' intentions to adopt the targeted SDM behaviours (P < 0.05). CONCLUSIONS: As perceived behavioural control seems to determine dieticians' and patients' adoption of SDM behaviours, interventions addressing barriers and reinforcing enablers of these behaviours are indicated. This exploratory study highlights issues that could be addressed in future research endeavours to expand the knowledge base relating to SDM adoption in dietetic practice. PMID- 25135145 TI - Fosterage as a system of dispersed cooperative breeding: evidence from the Himba. AB - Humans are obligate cooperative breeders, relying heavily on support from kin to raise children. To date, most studies of cooperative breeding have focused on help that supplements rather than replaces parental care. Here we propose that fosterage can act as a form of dispersed cooperative breeding, one that enhances women's fitness by allowing them to disinvest in some children and reallocate effort to others. We test this hypothesis through a series of predictions about the costs and benefits of fosterage for mothers, foster parents, and foster children using data from the Himba, a group of Namibian agro-pastoralists. We show that fostering out children enhances mothers' fitness, and we provide evidence for a causal link from fosterage to enhanced fitness by showing that fosterage of early-born children is associated with greater maternal reproductive success. Foster parents minimize the costs of fosterage by skewing their care toward their postreproductive years, and by mainly fostering close kin. However, the system is associated with some detrimental effects on foster children, who are more likely to be stunted and underweight than their non-fostered counterparts. PMID- 25135146 TI - The physiologic effects of pain on the endocrine system. AB - Severe pain has profound physiologic effects on the endocrine system. Serum hormone abnormalities may result and these serve as biomarkers for the presence of severe pain and the need to replace hormones to achieve pain control. Initially severe pain causes a hyperarousal of the hypothalamic-pituitary-adrenal system which results in elevated serum hormone levels such as adrenocorticotropin, cortisol, and pregnenolone. If the severe pain does not abate, however, the system cannot maintain its normal hormone production and serum levels of some hormones may drop below normal range. Some hormones are so critical to pain control that a deficiency may enhance pain and retard healing. PMID- 25135148 TI - Knowledge about Pain Clinics and Pain Physician among General Practitioners: A Cross-sectional Survey. AB - INTRODUCTION: There is an on-going debate about what qualifies one to be called a "pain physician" and who can run the "pain clinic". Currently, the discipline of anesthesiology is producing the majority of pain physicians. A literature search was unable to find data for any Pakistani or other South Asian countries with regards to general practitioner (GP) knowledge about pain clinics and pain physicians. The main objective of this study was to assess the awareness of GPs regarding the existence of the pain clinic and pain physician. METHODS: A total of 411 GPs were included in this cross-sectional survey. A questionnaire consisting of ten questions was designed to identify their knowledge about the existence of pain clinics and pain physicians. Questionnaires were completed in the field and edited for the inconsistencies and in-completeness. RESULTS: The results showed that only 52.6% of GPs were aware of the existence of pain clinics. The survey showed that 37.5% believe neurologists are the pain physicians and only 10.9% know that pain clinics are run by anesthesiologist. The vast majority (85.0%) are unaware of the modern pain relieving methods used in pain clinics. CONCLUSION: The survey indicates that nearly half of the GPs are unaware of the existence of pain clinics and pain physicians, and the majority of GPs are unaware of new pain relieving methods. PMID- 25135149 TI - Pain intensity and its association with negative mood States in patients with spinal cord injury. AB - INTRODUCTION: Chronic and persistent pain is a prevalent and debilitating secondary condition in patients with a neurological injury such as spinal cord injury (SCI). Patients with SCI have an increased risk of developing other co morbid conditions such as elevated negative mood states. Arguably, the presence of chronic pain would act to intensify the chances of developing negative mood states as opposed to resilient mental states. The objective of this research was to investigate the association between pain intensity and levels of negative mood states in adult patients with SCI. METHODS: Participants included 107 adults with SCI living in the community who completed an assessment regimen in a relaxed environment. Mean pain intensity over a period of 1 week and the Profile of Mood States, a validated psychometric measure of mood states (anxiety, depressed mood, anger, vigor, fatigue, confusion and total negative mood score) were used to determine associations between pain intensity and mood states. The sample was divided into a low pain intensity sub-group (<4 where 0 = no pain; 10 = worst pain imaginable) and a clinically significant or high pain intensity sub-group (>=4), allowing negative mood to be compared between the sub-groups. RESULTS: Mean age was 47.1 years, and 87% of the sample was male. Clinically significant pain intensity over the week prior to assessment was found in 52% of the 107 participants. The high pain intensity sub-group was found to have significantly elevated anxiety, depressed mood, anger, fatigue, confusion and significantly reduced vigor. CONCLUSION: These results provide further evidence that patients with SCI experience clinically elevated negative mood states if they have intense levels of pain over extended periods of time. In contrast, patients without intense pain have mood states similar to those in the able-bodied community. Implications for the treatment of SCI are discussed. PMID- 25135150 TI - An evaluation of total disintegration time for three different doses of sublingual fentanyl tablets in patients with breakthrough pain. AB - INTRODUCTION: Breakthrough pain is common among patients with cancer and presents challenges to effective pain management. Breakthrough pain is characterized by rapid onset, severe intensity, and duration typically lasting <1 h. Thus, optimal relief from breakthrough pain is best attained by administering analgesics with dissolution times and bioavailabilities that closely match the onset and duration of breakthrough pain. The objective of this study was to assess complete disintegration time of three different doses of sublingual fentanyl tablets in opioid-tolerant patients. METHODS: This was a single-center, non-randomized, open label study. Opioid-tolerant adult patients (N = 30) with chronic pain were assigned to one of three dose groups and self-administered a single 100, 200, or 300 MUg sublingual fentanyl tablet (Abstral((r)), Galena Biopharma, Portland, OR, USA). Time to complete disintegration was measured by each patient with a stopwatch and independently verified by study personnel. RESULTS: Disintegration time (mean +/- SD) for sublingual fentanyl tablets (all doses) was 88.2 +/- 55.1 s. Mean disintegration times tended to be slightly longer for the 200 MUg (96.7 +/- 57.9 s) and 300 MUg doses (98.6 +/- 64.8 s) compared to the 100 MUg dose (69.5 +/- 40.5 s). Differences were not statistically significant. Disintegration time was not significantly different between men and women and was not affected by age. CONCLUSION: Sublingual fentanyl tablets dissolved rapidly (average time <2 min) in all patients, with the higher doses taking slightly more time to dissolve. PMID- 25135147 TI - Management of fibromyalgia syndrome: review of evidence. AB - Fibromyalgia syndrome (FMS) is a common chronic musculoskeletal pain disorder of unknown etiology and characterized by generalized body pain, hyperalgesia, and other functional and emotional comorbidities. Despite extensive research, no treatment modality is effective for all FMS patients. In this paper, we briefly review the history of FMS and diagnostic criteria, and potential pathophysiological mechanisms including central pain modulation, neurotransmitters, sympatho-adrenal and hypothalamic-pituitary-adrenal systems and peripheral muscle issues. The primary focus of the paper is to review treatment options for managing fibromyalgia symptoms. We will discuss FDA approved medications and other pharmacologic agents, and non-pharmacologic treatments that have shown promising effects. PMID- 25135151 TI - Complex regional pain syndrome treated with intravenous immunoglobulin in a patient with common variable immune deficiency. AB - INTRODUCTION: Common variable immunodeficiency (CVID) represents a large heterogeneous group of antibody-deficiency syndromes associated with a wide range of clinical features and a lack of defined causes in the realm of primary immunodeficiencies. Here, we present a case of CVID in a 62-year-old white male patient with a history of longstanding complex regional pain syndrome (CRPS). CASE PRESENTATION: His medical history included multiple sinus infections per year and several pneumonias requiring antibiotics. He has had various back surgeries, including a laminectomy at the L4 level 1 year prior to his diagnosis. Thereafter, he underwent four sympathetic nerve blocks with minimal pain relief. Blood chemistries showed a normal white blood cell count with a normal differential, but increased erythrocyte sedimentation rate and C-reactive protein levels. Total Ig (Immunoglobulin)G was 611 mg/dL (normal 700-1,600), IgG1 was 425 mg/dL (341-894), IgG2 was 114 mg/dL (171-632), IgG3 was 14.4 mg/dL (18.4-106), and IgG4 was 7.4 mg/dL (2.4-121). IgA was 47 mg/dL (normal 70-400), IgM was 131 mg/dL (40-230), and IgE was 4.5 kU/L (<4.0). He only had 10 of 23 pneumococcal titers in the protective range post-vaccination. Upon treatment of the CVID with intravenous immunoglobulin, the patient's pain levels were significantly decreased and have been maintained for more than 2 years. CONCLUSION: Therefore, immunoglobulin therapy appears to have been beneficial in the treatment of the patient's symptoms of CRPS, including pain. Additional studies investigating the mechanism by which immunoglobulin therapy may reduce the inflammation and pain of CRPS are needed. PMID- 25135152 TI - Erratum to: Effects of a Single Session Group Intervention for Pain Management in Chronic Pain Patients: A Pilot Study. PMID- 25135153 TI - Cryptococcosis-related deaths and associated medical conditions in the United States, 2000-2010. AB - Cryptococcosis is an invasive mycotic infection primarily affecting immunocompromised individuals. The objective of this study was to describe cryptococcosis mortality and associated medical conditions in the US for the period 2000-2010. Cryptococcosis-related deaths were identified from the national multiple-cause-of-death dataset. Mortality trends and comparison analyses were performed on overall cases of cryptococcosis and by subset [i.e. clinical manifestations of disease and human immunodeficiency virus (HIV) status]. A matched case-control analysis was also conducted to describe the associations between this disease and comorbid medical conditions. A total of 3210 cryptococcosis-related deaths were identified. Cerebral cryptococcosis was the most commonly reported clinical manifestation of the disease. Approximately one fifth of the decedents (n = 616) had a co-diagnosis of HIV. Mortality rates were highest among men, blacks, Hispanics, Native Americans and older adults. Poisson regression analysis indicated a 6.52% annual decrease in mortality rates for the study period. HIV (MOR = 35.55, 95% CI 27.95-45.22) and leukaemia (MOR = 16.10, 95% CI 11.24-23.06) were highly associated with cryptococcosis-related deaths. Cryptococcosis mortality declined significantly during 2000-2010. However, the disease continues to cause appreciable mortality in the US. With the majority of decedents having no HIV co-diagnosis, there is still much to be learned about the epidemiology of this mycosis. PMID- 25135154 TI - Identifying sources of emerging organic contaminants in a mixed use watershed using principal components analysis. AB - Principal components analysis (PCA) was used to identify sources of emerging organic contaminants in the Zumbro River watershed in Southeastern Minnesota. Two main principal components (PCs) were identified, which together explained more than 50% of the variance in the data. Principal Component 1 (PC1) was attributed to urban wastewater-derived sources, including municipal wastewater and residential septic tank effluents, while Principal Component 2 (PC2) was attributed to agricultural sources. The variances of the concentrations of cotinine, DEET and the prescription drugs carbamazepine, erythromycin and sulfamethoxazole were best explained by PC1, while the variances of the concentrations of the agricultural pesticides atrazine, metolachlor and acetochlor were best explained by PC2. Mixed use compounds carbaryl, iprodione and daidzein did not specifically group with either PC1 or PC2. Furthermore, despite the fact that caffeine and acetaminophen have been historically associated with human use, they could not be attributed to a single dominant land use category (e.g., urban/residential or agricultural). Contributions from septic systems did not clarify the source for these two compounds, suggesting that additional sources, such as runoff from biosolid-amended soils, may exist. Based on these results, PCA may be a useful way to broadly categorize the sources of new and previously uncharacterized emerging contaminants or may help to clarify transport pathways in a given area. Acetaminophen and caffeine were not ideal markers for urban/residential contamination sources in the study area and may need to be reconsidered as such in other areas as well. PMID- 25135155 TI - Letter from the editor. PMID- 25135157 TI - Comparison of circumferential pulmonary vein isolation and antiarrhythmic drug therapy in patients with atrial fibrillation. AB - INTRODUCTION: The aim of this study was to evaluate quality of life after circumferential pulmonary vein isolation (CPVI) compared with antiarrhythmic drug therapy (ADT) in treating atrial fibrillation (AF). CPVI is now a common therapy in AF, but few studies have focused on the effect of CPVI on quality of life. METHODS: A total of 123 AF patients were followed prospectively. Quality of life was evaluated comparing CPVI with ADT as a second-line treatment for patients with AF. The Medical Outcomes Study Short Form (SF)-36 health surveys were conducted to establish a baseline score before initiation and again at 6 months after the intervention. RESULTS: Mean follow-up duration was 12.7 +/- 4.3 months. Of 123 patients enrolled, 66 were randomized to receive CPVI and 57 to ADT alone. At the 6-month follow-up, 13 (22.8%) patients in the ADT group and 41 (62.1%) patients in the CPVI group had no recurrence of AF. The SF-36 scales were significantly higher in the CPVI than in the ADT group, as were the physical component summary scores (269.3 +/- 58.6 vs. 234.9 +/- 66.9) and mental component summary scores (273.6 +/- 69.4 vs. 234.1 +/- 44.7). Quality of life was significantly higher in the CPVI group (except for body pain). CONCLUSION: In patients with AF, CPVI has superiority over ADT with regards to the maintenance of sinus rhythm and improvements in quality of life. PMID- 25135156 TI - Effect of thermal therapy using hot water bottles on brain natriuretic Peptide in chronic hemodialysis patients. AB - INTRODUCTION: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The present study assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with CHF. METHODS: Plasma brain natriuretic peptide (BNP) levels were evaluated in 98 hemodialysis patients in a clinic. Nine patients whose BNP levels were >500 pg/mL agreed to be enrolled in the study and received thermal therapy using hot water bottles. RESULTS: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 +/- 448 to 680 +/- 339 pg/mL), but the difference was not significant (P = 0.0845). The oral temperature changed from 36.44 +/- 0.45 degrees C to 37.04 +/- 0.48 degrees C (+0.597 degrees C, P < 0.0001). No side effects were experienced during the therapy. Moreover, most patients had an improvement in their symptoms and the ability to perform activities of daily living. CONCLUSION: Thermal therapy using hot water bottles is very safe and tends to reduce plasma BNP levels in hemodialysis patients with CHF. PMID- 25135158 TI - Lercanidipine effect on polymorphonuclear leukocyte-related inflammation and insulin resistance in essential hypertension patients. AB - INTRODUCTION: Inflammation, insulin resistance, and oxidative stress (OS) are among the mechanisms that have been implicated in the pathogenesis of essential hypertension (EH). Peripheral polymorphonuclear leukocytes (PMNLs) are primed in EH patients, releasing uncontrolled superoxide anions contributing to OS in these patients. PMNL priming correlates with insulin resistance and PMNL intracellular calcium ([Ca(2+)]i). Recent studies have attributed additional anti-ischemic and antioxidative characteristics to the antihypertensive drug, lercanidipine, a third-generation calcium-channel blocker. The purpose of this study was to evaluate the possible nontraditional effect of 2 months of lercanidipine treatment on insulin resistance and on PMNL-related inflammation in EH patients. METHODS: Non-smoking EH patients with untreated mild-to-moderate high blood pressure (BP) were included. Low-grade inflammation was reflected by PMNL apoptosis and by white blood cell (WBC) and PMNL counts. Systemic inflammation was measured by plasma fibrinogen, C-reactive protein (CRP), and transferrin and albumin levels. Fasting serum insulin levels served as a marker of insulin resistance. RESULTS: Two months of lercanidipine treatment showed a significant decrease in BP, WBC, and PMNL counts, PMNL apoptosis, CRP, and serum insulin levels, and a significant increase in serum albumin levels. Rates of superoxide release from PMNLs, WBC and PMNL counts, and insulin levels positively correlated with mean arterial BP values. CONCLUSION: The use of lercanidipine can be favorable in EH patients due to its combined anti-PMNL priming and anti inflammatory effects, in addition to its antihypertensive characteristics. PMID- 25135159 TI - Transcatheter pulmonary valve replacement. AB - Transcatheter pulmonary valve replacement (tPVR) has evolved into a viable alternative to surgical conduit or bioprosthetic valve replacement. This procedure has paved the way for a more advanced approach to congenital and structural interventional cardiology. Although many successes have been noted, there are still a number of challenges with this procedure, including large delivery systems, the need for a conduit or a bioprosthetic valve as a landing zone for the valve, optimal timing of the procedure to prevent right ventricular failure, arrhythmias, and possible death. Research is ongoing to broaden the use of this technology when treating patients with dilated right ventricular outflow tracts, and early experience with a self-expanding valve model has been reported. Affordability is an important factor that must be considered especially in developing nations. The aim of this review is to emphasize the advancement of tPVR, the benefits and challenges of valve implantation, the current state, and the future innovations associated with this approach. PMID- 25135162 TI - Programmable ionic conductance in a pH-regulated gated nanochannel. AB - An analytical model for the ionic conductance in a pH-regulated nanochannel gated by a field effect transistor is derived for the first time. In contrast to the existing studies, the developed model takes into account the practical effects of multiple ionic species, surface chemistry reactions, the Stern layer, and electroosmotic flow. The model is validated by the experimental data of ionic conductance available in the literature. Results show that the performance of the field effect control of the ionic conductance in the gated silica nanochannel is remarkable when the solution pH and salt concentration are low. In addition, the Stern layer effect on the ionic conductance is significant when the salt concentration is low. PMID- 25135160 TI - The Edwards SAPIEN Transcatheter Heart Valve for Calcific Aortic Stenosis: A Review of the Valve, Procedure, and Current Literature. AB - The Edwards SAPIENTM transcatheter heart valve (Edwards Lifesciences LLC, Irvine, CA, USA) is approved by the US Food and drug administration for use in the aortic position in patients with severe aortic stenosis who are not surgical candidates. This approval was backed by data from the Placement of AoRTic TraNscathetER Valve (PARTNER) I clinical trial, which showed the valve to be superior to standard medical therapy in high-risk nonoperative patients in cohort B of the trial. Although insertion of the valve is considered to be very safe, stroke, major vascular complications, and conduction abnormalities are the most frequent procedural complications. A dedicated team of physicians trained in structural cardiac interventions, including two interventional cardiologists, an echocardiographer, and a cardiac surgeon, are involved in every case. Improvements in valve design and streamlining of the delivery system, as well as favorable long-term outcomes, will hopefully pave the way for wider patient use in the future. PMID- 25135161 TI - Positioning high-dose radiation in multidisciplinary management of unresectable cholangiocarcinomas: review of current evidence. AB - Cholangiocarcinoma is a rare malignancy of the bile ducts. The current standard of care for unresectable nonmetastatic disease is doublet systemic chemotherapy, which provides a median survival of 11.7 months. Although chemoradiation is a therapeutic option that provides almost equivalent or superior survival, the lack of level I evidence presents a major hurdle in routinely recommending it within multidisciplinary clinics. This mini review presents the current evidence on the use of chemoradiation for unresectable nonmetastatic cholangiocarcinoma and rationale for positioning it within multidisciplinary management of unresectable cholangiocarcinomas. PMID- 25135164 TI - Epigenetic marks in estrogen receptor alpha CpG island correlate with some reproductive risk factors in breast cancer. AB - Reproductive backgrounds, such as age at menarche and menopause, age of first full-term pregnancy (FFTP), number of full-term deliveries and oral contraceptive use are main hormone-related risk factors of breast cancer. It seems that the mentioned factors may affect the risk of breast cancer by enhancing the duration of exposure to estrogen as a potent carcinogen for breast tissue, but the molecular mechanism which links each risk factor to breast cancer is unclear. Estrogen mainly works via its nuclear receptor (ERalpha). As epigenetic alterations such as CpG methylation are potential links between endogenous or exogenous exposures and genome, we hypothesized that hormone-related risk factors may correlate with the epigenetic marks of the ERalpha promoter in breast tumors. In the present study, the CpG methylation status of the ERalpha gene in 99 samples of breast tumors belonged to women with different reproductive histories was evaluated. The reproductive history data were collected from patients. ERalpha CpG methylation was investigated by methylation specific PCR in DNA samples were obtained from the breast tumors. We could show that some of the hormone-related risk factors (early FFTP and increased number of pregnancies) were inversely correlated with epigenetic marks in ERalpha gene in breast tumors. Other hormone-related risk factors such as age of menarche and menopause and oral contraceptive use did not show any association with ERalpha methylation. It seems that pregnancy-related risk factors in comparison with other hormone-related factors work via different mechanism. As ERalpha methylation is a poor prognosis marker in breast tumors, its association with some modifiable reproductive risk factors (FFTP age and numbers of pregnancies) reiterates the importance of programming reproductive life style not only for prevention of breast cancer but also in favoring the prognosis of the affected women. The exact molecular mechanisms of the observed correlation need more investigation in the future. PMID- 25135165 TI - Major atmospheric emissions from peat fires in Southeast Asia during non-drought years: evidence from the 2013 Sumatran fires. AB - Trans-boundary haze events in Southeast Asia are associated with large forest and peatland fires in Indonesia. These episodes of extreme air pollution usually occur during drought years induced by climate anomalies from the Pacific (El Nino Southern Oscillation) and Indian Oceans (Indian Ocean Dipole). However, in June 2013--a non-drought year--Singapore's 24-hr Pollutants Standards Index reached an all-time record 246 (rated "very unhealthy"). Here, we show using remote sensing, rainfall records and other data, that the Indonesian fires behind the 2013 haze followed a two-month dry spell in a wetter-than-average year. These fires were short-lived (one week) and limited to a localized area in Central Sumatra (1.6% of Indonesia): burning an estimated 163,336 ha, including 137,044 ha (84%) on peat. Most burning was confined to deforested lands (82%; 133,216 ha). The greenhouse gas (GHG) emissions during this brief, localized event were considerable: 172 +/- 59 Tg CO2-eq (or 31 +/- 12 Tg C), representing 5-10% of Indonesia's mean annual GHG emissions for 2000-2005. Our observations show that extreme air pollution episodes in Southeast Asia are no longer restricted to drought years. We expect major haze events to be increasingly frequent because of ongoing deforestation of Indonesian peatlands. PMID- 25135163 TI - Radionuclide imaging of cardiac sympathetic innervation in heart failure: unlocking untapped potential. AB - Heart failure (HF) is associated with sympathetic overactivity, which contributes to disease progression and arrhythmia development. Cardiac sympathetic innervation imaging can be performed using radiotracers that are taken up in the presynaptic nerve terminal of sympathetic nerves. The commonly used radiotracers are (123)I-metaiodobenzylguanidine ((123)I-mIBG) for planar and single-photon emission computed tomography imaging, and (11)C-hydroxyephedrine for positron emission tomography imaging. Sympathetic innervation imaging has been used in assessing prognosis, response to treatment, risk of ventricular arrhythmias and sudden death and prediction of response to cardiac resynchronization therapy in patients with HF. Other potential applications of these techniques are in patients with chemotherapy-induced cardiomyopathy, predicting myocardial recovery in patients with left ventricular assist devices, and assessing reinnervation following cardiac transplantation. There is a lack of standardization with respect to technique of (123)I-mIBG imaging that needs to be overcome for the imaging modality to gain popularity in clinical practice. PMID- 25135166 TI - Exosome analysis: a promising biomarker system with special attention to saliva. AB - Today, exosome-related studies have become a focus in science and technology. Recently, three scientists won the Nobel Prize for determining the mechanisms of exosomal transport, making exosomes a promising biomarker system for disease diagnosis and treatment. This review provides a general introduction of exosomes and explores the recent progress on the function, application, isolation, and identification of exosomes as biomarkers in blood and other body fluids, especially in saliva. Detailed information of exosomal proteins and RNAs is discussed in the paper because of their ability to determine the function of exosomes. Due to their noninvasive assessment for quick and convenient diagnosis of diseases, salivary exosomes may well be promising biomarkers. PMID- 25135167 TI - A double-pulse approach for electrotransfection. AB - Gene transfer and expression can be obtained by delivering calibrated electric pulses on cells in the presence of plasmids coding for the activity of interest. The electric treatment affects the plasma membrane and induces the formation of a transient complex between nucleic acids and the plasma membrane. It results in a delivery of the plasmid in the cytoplasm. Expression is only obtained if the plasmid is translocated inside the nucleus. This is a key limit in the process. We previously showed that delivery of a high-field short-duration electric pulse was inducing a structural alteration of the nuclear envelope. This study investigates if the double-pulse approach (first pulse to transfer the plasmid to the cytoplasm, and second pulse to induce the structural alteration of the envelope) was a way to enhance the protein expression using the green fluorescent protein as a reporter. We observed that not only the double-pulse approach induced the transfection of a lower number of cells but moreover, these transfected cells were less fluorescent than the cells treated only with the first pulse. PMID- 25135169 TI - Accelerated biodegradation of selected nematicides in tropical crop soils from Costa Rica. AB - Degradation and mineralization behavior of selected nematicides was studied in soil samples from fields cultivated with banana, potato, and coffee. Degradation assays in most of the studied soils revealed shorter half-lives for carbofuran (CBF) and ethoprophos (ETP) in samples with a history of treatment with these compounds, which may have been caused by enhanced biodegradation. A short half life value for CBF degradation was also observed in a banana field with no previous exposure to this pesticide, but with a recent application of the carbamate insecticide oxamyl, which supports the hypothesis that preexposure to oxamyl may cause microbial adaptation towards degradation of CBF, an observation of a phenomenon not yet tested according to the literature reviewed. Mineralization assays for CBF and terbufos (TBF) revealed that history of treatment with these nematicides did not cause higher mineralization rates in preexposed soils when compared to unexposed ones, except in the case of soils from coffee fields. Mineralization half-lives for soils unexposed to these pesticides were significantly shorter than most reports in the literature in the same conditions. Mineralization rates for soils with a previous exposure to these pesticides were also obtained, adding to the very few reports found. This paper contributes valuable data to the low number of reports dealing with pesticide fate in soils from tropical origin. PMID- 25135168 TI - Toxicity and oxidative stress induced by used and unused motor oil on freshwater microalga, Pseudokirchneriella subcapitata. AB - Although used motor oil from automobiles is one of the major pollutants through storm water in urban environments leading to contamination of water bodies, very little information is available on its toxicity towards growth of microalgae. Also, to our knowledge, there are no data on the used motor oil-induced oxidative stress in microalgae. We therefore investigated the toxicity of used and fresh motor oil on growth and antioxidant enzymes of a microalga, Pseudokirchneriella subcapitata. In general, used oil was more toxic to the alga than fresh oil. Used oil at 0.20 % inhibited algal growth, measured in terms of chlorophyll a, by 44 % while fresh oil was nontoxic up to 2.8 %. Water-accommodated fraction (WAF) of the used oil at >50 % concentration exhibited significant toxicity while WAF from fresh oil was nontoxic even up to 100 %. Used oil and its WAF, even at lower concentrations, increased the levels of antioxidant enzymes indicating algal response to the toxicity stress. When the alga was exposed to WAF from fresh motor oil, no alterations in the antioxidant enzyme levels were evident. The present investigation suggests that contamination of aquatic systems with used oil could potentially affect the ecosystem health via disruption of primary producers that are located at the base of the food chain. PMID- 25135170 TI - Effects on inorganic nitrogen compounds release of contaminated sediment treatment with in situ calcium nitrate injection. AB - Notable releases of nitrate, nitrite, and ammonia are often observed in contaminated sediment treatment works implementing in situ calcium nitrate injection. In order to provide extended information for making best decision of employing this in situ sediment remediation technology, in this study the releases of nitrate, nitrite, and ammonia from the sediment after the calcium nitrate addition operation was investigated in column setups designed to simulate the scenarios of a stagnant water (e.g., a pound or small lake) and a tidal influenced water (e.g., a river mouth), respectively. Comparison with published aquatic toxicity data or authorized criteria was conducted to assess if there is any toxic effect that might be induced. Along with the vigorous N2 emission due to the denitrification reactions which occurred in the treated sediment, external loaded nitrate, intermediately produced nitrite, and indigenous ammonia in the sediment showed being mobilized and released out. Their promoted release and fast buildup in the overlying water to an excessive level probably cause toxic effects to sensitive freshwater living species. Among them, the potential ecological risk induced by the promoted sediment ammonia release is the greatest, and cautions shall be raised for applying the calcium nitrate injection in ammonia-rich sediments. The caused impacts shall be less violent in a tidal-influenced water body, and comparatively, the continuous and fast accumulation of the released inorganic nitrogen compounds in a stagnant water body might impose severer influences to the ecosystem until being further transferred to less harmful forms. PMID- 25135171 TI - Transformation of anthracene on various cation-modified clay minerals. AB - In this study, anthracene was employed as a probe to explore the potential catalytic effect of clay minerals in soil environment. Clay minerals saturated with various exchangeable cations were tested. The rate of anthracene transformation follows the order: Fe-smectite >> Cu-smectite > Al-smectite ~ Ca smectite ~ Mg-smectite ~ Na-smectite. This suggests that transition-metal ions such as Fe(III) play an important role in anthracene transformation. Among Fe(III)-saturated clays, Fe(III)-smectite exhibits the highest catalytic activity followed by Fe(III)-illite, Fe(III)-pyrophyllite, and Fe(III)-kaolinite, which is in agreement with the interlayer Fe(III) content. Moreover, effects by two common environmental factors, pH and relative humidity (RH), were evaluated. With an increase in pH or RH, the rate of anthracene transformation decreases rapidly at first and then is leveled off. GC-MS analysis identifies that the final product of anthracene transformation is 9,10-anthraquinone, a more bioavailable molecule compared to anthracene. The transformation process mainly involves cation-pi bonding, electron transfer leading to cation radical, and further oxidation by chemisorbed O2. The present work provides valuable insights into the abiotic transformation and the fate of PAHs in the soil environment and the development of contaminated land remediation technologies. PMID- 25135172 TI - Mesh repair versus non-mesh repair for strangulated inguinal hernia: systematic review with meta-analysis. AB - BACKGROUND: The optimal technique to cure strangulated inguinal hernia remains controversial. The use of mesh in cases of strangulated hernia is still debated due to the potential risk of infection. OBJECTIVE: This systematic review aimed to determine whether or not the mesh repair technique is associated with a higher risk of surgical site infection than non-mesh techniques for strangulated inguinal hernias in adults. METHODS: An electronic search of the relevant literature was performed on 15 December 2012 using the following databases: MEDLINE, the Cochrane Library, Scopus, Embase, and the Web of Science. Articles reporting a comparison between the mesh repair technique and a non-mesh technique to treat strangulated inguinal hernias in adults, and published in the English or French language in a peer-reviewed journal, were considered for analysis. The quality of randomized controlled trials (RCTs) was assessed using the Jadad scoring system. To assess the quality of non-randomized trials, we used the Methodological Index for Non-Randomized Studies (MINORS). RESULTS: A total of 232 papers was found in the initial search; nine were included in the meta-analysis. The wound infection rate in the mesh repair technique group was lower than in the control group, with a trend towards significance (odds ratio [OR] 0.46, 95 % confidence interval [CI] 0.20-1.07; p = 0.07). The hernia recurrence rate was lower in the mesh repair group (OR 0.2, 95 % CI 0.05-0.78; p = 0.02). CONCLUSION: The mesh repair technique is a good option for the treatment of strangulated inguinal hernias in adults, giving an acceptable wound infection rate and fewer recurrences than non-mesh repair. Our study does not allow us to recommend the use of mesh in cases of bowel resection. We emphasize that, except the two RCTs, the results are predicated on patient selection bias by careful surgeons. Further RCTs are required to obtain more powerful evidence-based data. PMID- 25135173 TI - Evaluation of QOL after proximal gastrectomy using a newly developed assessment scale (PGSAS-45). AB - BACKGROUND: Proximal gastrectomy with esophagogastrostomy (PGEG) has been widely applied as a comparatively simple method. In this study, we used a questionnaire survey to evaluate the influence of various surgical factors on post-operative quality of life (QOL) after PGEG. METHODS: In this post-gastrectomy syndrome assessment study, we analyzed QOL in 2,368 cases. Among these, 193 had undergone proximal gastrectomy and 115 had undergone PGEG. The Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-45 is a questionnaire consisting of 45 items, including the SF-8, the Gastrointestinal Symptom Rating Scale (GSRS), and other symptom items seemed to be specific to post-gastrectomy. The 23 symptom items were composed of seven symptom subscales (SS), including esophageal reflux, abdominal pain, and meal-related distress. These seven SS, total symptom score, ingested amount of food per meal, necessity for additional meals, quality of ingestion SS, ability to work, dissatisfaction with symptoms, dissatisfaction with the meal, dissatisfaction with working, dissatisfaction with daily life SS and change in body weight were evaluated as main outcome measures. In PGEG cases, we evaluated the influence on QOL of various surgical factors, such as procedures to prevent gastroesophageal regurgitation and size of the remnant stomach. RESULTS: The scores for esophageal reflux and dissatisfaction with the meal were higher in patients who had not undergone an anti-reflux procedure. In most cases, the preserved remnant stomach was more than two-thirds the size of the pre-operative stomach. When comparing patients with a remnant stomach two-thirds the pre operative size and those with more than three-quarters, the diarrhea SS and necessity for additional meals scores were lower in the group with more than three-quarters. The indigestion, constipation, and abdominal pain subscales, and the total symptom score, were higher in patients who had not undergone pyloric bougie than in those who had. CONCLUSION: These results indicated that QOL was better in patients with a large remnant stomach. Procedures to prevent gastroesophageal reflux, and the use of pyloric bougie as a complementary drainage procedure, were considered effective ways to reduce the deterioration of QOL. PMID- 25135174 TI - What is the better choice for T1b gallbladder cancer: simple versus extended cholecystectomy. AB - BACKGROUND: There is debate over whether T1b gallbladder cancer (GBC) should be treated by simple cholecystectomy (SC) or by extended cholecystectomy (EC). The aim of this study is to compare and analyze the results of these two procedures. PATIENTS AND METHODS: The archived medical records of 805 patients with GBC who had undergone surgical resection in Asan Medical Center, or were referred from other hospitals after undergoing surgery, between 1997 and 2010 were retrospectively reviewed. Of these, 85 patients were diagnosed with pathologic stage T1b (muscular layer) GBC. By using propensity scoring, the EC group and the SC group were matched in the proportion of 1:2; so, 54 patients were enrolled in this study. RESULTS: Among the 54 pathologic stage T1b cancer patients, SC was performed in 36 (66.7 %) and EC in 18 (33.4 %). The mean operation time and hospital stay after surgery of the SC group was significantly shorter than in the EC group (83.2 vs. 356.4 min, 7.8 vs. 15.2 days; both p = 0.000). Disease recurrence was noted in four cases (11.1 %), all in the SC group; 50 % of recurred patients experienced recurrence at the lymph node. There was no significant intergroup difference in the 5-year survival rate (5-YSR) (88.8 % for SC vs. 93.3 % for EC, p = 0.521). CONCLUSIONS: In this study, for stage T1b GBC, both EC and SC offered similar cure rates. However, recurrence is associated with SC and inadequate lymph node dissection (LND). Therefore, EC including regional LND may be justified and preferred because of the possibility of lymph node metastasis and the accurate assessment of stage (LN status), except that the patients have a high risk of operation. PMID- 25135175 TI - Congenital anomalies in low- and middle-income countries: the unborn child of global surgery. AB - Surgically correctable congenital anomalies cause a substantial burden of global morbidity and mortality. These anomalies disproportionately affect children in low- and middle-income countries (LMICs) due to sociocultural, economic, and structural factors that limit the accessibility and quality of pediatric surgery. While data from LMICs are sparse, available evidence suggests that the true human and financial cost of congenital anomalies is grossly underestimated and that pediatric surgery is a cost-effective intervention with the potential to avert significant premature mortality and lifelong disability. PMID- 25135176 TI - Liver-to-spleen ratio as an index of chronic liver diseases and safety of hepatectomy: a pilot study. AB - BACKGROUND: Hepatic failure is a main cause of death after hepatectomy. Accurate preoperative evaluation of functional liver reserve is the key to ensure safe resection. Studies have found that the spleen would gradually enlarge as chronic liver disease worsened. This study was designed to determine whether preoperative liver-to-spleen ratio (LSR) would be an indicator to evaluate severity of liver disease and predict safety of hepatectomy. METHODS: The volumes of liver and spleen were evaluated on computed tomography scan in 67 patients who received partial hepatectomy. Preoperative LSR was calculated. Statistical analysis was conducted to examine the relationship between LSR and the degree of chronic liver disease. Ability of LSR to predict the safety of hepatectomy also was evaluated. RESULTS: LSR had a negative correlation with the degree of chronic liver diseases (r = -0.606, P < 0.0001). LSR = 3.22 was the cutoff point for predicting posthepatectomy complications and inadequacy. AUC, sensitivity, and specificity for predicting posthepatectomy complications and inadequacy respectively were 0.830 (95 % confidence interval [CI] 0.715-0.950, P < 0.0001), 69.6, 93.2 %, and 0.863 (95 % CI 0.777-0.949, P < 0.0001), 68.8, 84.3 %. Multivariate analysis showed that LSR = 3.22 was the factor that affected both posthepatectomy complications and liver inadequacy. CONCLUSIONS: Preoperative LSR score correlated well with the degree of chronic liver diseases, and it probably help us to improve the safety of hepatectomy. PMID- 25135177 TI - The extent of hepatectomy does not affect physical QOL in patients with HCC: reply. PMID- 25135178 TI - Cardiovascular and cancer events in hyper-high-density lipoprotein cholesterolemic patients: a post hoc analysis of the MEGA study. AB - BACKGROUND: The prognosis for hyper-high-density lipoprotein (HDL) cholesterolemic patients has not been fully elucidated. We conducted a post hoc analysis of MEGA study data to investigate prospectively the incidence of cardiovascular events and cancer in hyper-HDL cholesterolemic patients. METHODS: A total of 7832 patients with mild hypercholesterolemia were randomly allocated to either the National Cholesterol Education Program step 1 diet alone (n = 3966) or the diet plus pravastatin (n = 3866) and followed for 5 years. The incidences of coronary heart disease (CHD), CHD plus cerebral infarction (CI), cardiovascular disease (CVD), and cancer were calculated using the Cox proportional hazards model according to the level of HDL cholesterol (HDL-C). RESULTS: CHD incidence was lower in patients with HDL-C >60-90 mg/dL (-52%, p = 0.0018) and HDL-C > 90 mg/dL (-46%, p = 0.4007) than in patients with HDL-C <= 60 mg/dL. The incidences of CHD, CHD plus CI, and CVD were significantly lower in patients with HDL-C >60-90 mg/dL than in those with HDL-C <= 60 mg/dL in both diet-alone and diet-plus-pravastatin groups. Cancer incidence was not increased in patients with HDL-C >60-90 mg/dL. CONCLUSION: Patients not receiving statin therapy should aim for a target HDL-C of between 60 and 90 mg/dL to achieve a significant reduction in CHD without the occurrence of adverse events. TRIAL REGISTRATION: Clinical trials.gov NCT00211705. PMID- 25135180 TI - Phenytoin-induced methaemoglobinaemia in a patient with glioblastoma multiforme. PMID- 25135179 TI - Convergence of a specialized root trait in plants from nutrient-impoverished soils: phosphorus-acquisition strategy in a nonmycorrhizal cactus. AB - In old, phosphorus (P)-impoverished habitats, root specializations such as cluster roots efficiently mobilize and acquire P by releasing large amounts of carboxylates in the rhizosphere. These specialized roots are rarely mycorrhizal. We investigated whether Discocactus placentiformis (Cactaceae), a common species in nutrient-poor campos rupestres over white sands, operates in the same way as other root specializations. Discocactus placentiformis showed no mycorrhizal colonization, but exhibited a sand-binding root specialization with rhizosheath formation. We first provide circumstantial evidence for carboxylate exudation in field material, based on its very high shoot manganese (Mn) concentrations, and then firm evidence, based on exudate analysis. We identified predominantly oxalic acid, but also malic, citric, lactic, succinic, fumaric, and malonic acids. When grown in nutrient solution with P concentrations ranging from 0 to 100 MUM, we observed an increase in total carboxylate exudation with decreasing P supply, showing that P deficiency stimulated carboxylate release. Additionally, we tested P solubilization by citric, malic and oxalic acids, and found that they solubilized P from the strongly P-sorbing soil in its native habitat, when the acids were added in combination and in relatively low concentrations. We conclude that the sand-binding root specialization in this nonmycorrhizal cactus functions similar to that of cluster roots, which efficiently enhance P acquisition in other habitats with very low P availability. PMID- 25135181 TI - Protoplast fusion enhances lignocellulolytic enzyme activities in Trichoderma reesei. AB - Protoplast fusion was used to obtain a higher production of lignocellulolytic enzymes with protoplast fusion in Trichoderma reesei. The fusant strain T. reesei JL6 was obtained from protoplast fusion from T. reesei strains QM9414, MCG77, and Rut C-30. Filter paper activity of T. reesei JL6 increased by 18% compared with that of Rut C-30. beta-Glucosidase, hemicellulase and pectinase activities of T. reesei JL6 were also higher. The former activity was 0.39 Uml(-1), while those of QM9414, MCG77, and Rut C-30 were 0.13, 0.11, and 0.16 Uml(-1), respectively. Pectinase and hemicellulase activities of JL6 were 5.4 and 15.6 Uml(-1), respectively, which were slightly higher than those of the parents. The effects of corn stover and wheat bran carbon sources on the cellulase production and growth curve of T. reesei JL6 were also investigated. PMID- 25135182 TI - Adult-onset vanishing white matter disease as differential diagnosis of primary progressive multiple sclerosis: a case report. AB - We report the case of a 42-year-old woman with a slowly progressive cerebellar syndrome. In contrast to a relatively mild clinical presentation, the magnetic resonance imaging (MRI) showed extensive leukencephalopathy with cystic degeneration. Initially primary progressive multiple sclerosis (PPMS) was suspected. Additional diffusion-weighted imaging revealed restricted diffusion in the white matter lesions with a reduced apparent diffusion coefficient. Genetic testing showed vanishing white matter disease (VWM) with c.260C>T EIF2B3 mutation. In conclusion, in cases with relatively mild symptoms and extensive white matter lesions, adult-onset VWM should be considered as differential diagnosis of PPMS and diffusion-weighted imaging may be helpful to identify suspected cases. PMID- 25135183 TI - Allopurinol initiation and change in blood pressure in older adults with hypertension. AB - Hypertension is a key risk factor for cardiovascular disease, and new treatments are needed. Uric acid reduction lowers blood pressure (BP) in adolescents, suggesting a direct pathophysiological role in the development of hypertension. Whether the same relationship is present in older adults is unknown. We explored change in BP after allopurinol initiation using data from the UK Clinical Practice Research Datalink. Data were extracted for patients with hypertension aged >65 years who were prescribed allopurinol with pretreatment and during treatment BP readings. Data from comparable controls were extracted. The change in BP in patients with stable BP medication was the primary outcome and was compared between groups. Regression analysis was used to adjust for potential confounding factors, and a propensity-matched sample was generated. Three hundred sixty-five patients who received allopurinol and 6678 controls were included. BP fell in the allopurinol group compared with controls (between-group difference in systolic and diastolic BP: 2.1 mm Hg; 95% confidence interval, -0.6 to 4.8; and 1.7 mm Hg; 95% confidence interval, 0.4-3.1, respectively). Allopurinol use was independently associated with a fall in both systolic and diastolic BP on regression analysis (P<0.001). Results were consistent in the propensity-matched sample. There was a trend toward greater fall in BP in the high-dose allopurinol group, but change in BP was not related to baseline uric acid level. Allopurinol use is associated with a small fall in BP in adults. Further studies of the effect of high-dose allopurinol in adults with hypertension are needed. PMID- 25135184 TI - Nitric oxide inhibition of endothelin-1 release in the vasculature: in vivo relevance of in vitro findings. PMID- 25135186 TI - Amplified fluorescence quenching of lucigenin self-assembled inside silica/chitosan nanoparticles by Cl-. AB - Fluorescence sensing of an analyte based on the fluorophore collective effect is a reliable, sensitive sensing approach. Many ultralow targets can be detected on the basis of the high sensitivity and signal amplification of the fluorescence sensing system. However, the complicated synthesis procedures, harsh conditions required to design and control the fluorescence molecular probes and conjugated chain length, and the higher cost of synthesis are still challenges. To address these issues, we developed a simple, rapid, and sensitive collective effect based fluorescence sensing platform. In this sensing platform, the fluorophore unit was self-assembled on the wall of the nanopores of the porous structural silica/chitosan nanoparticles (SCNPs) on the basis of the electrostatic interaction and supermolecular interaction between the fluorophores and SiO(-) groups and chitosan. Since these self-assembled fluorophores are close enough to communicate with each other on the basis of the space confinement effect of the pore size, many fluorophore units could interact with a single analyte and produce an amplified fluorescence sensing ability. Chloride ion, an important anion in biological fluids, and lucigenin, a typical fluorescent dye, were used as a model to confirm the proof-of-concept strategy. Our results showed that, compared to free-state lucigenin in solution, the assembled-state lucigenin in SCNPs presented an about 10-fold increase in its Stern-Volmer constant when the concentration of Cl(-) was lower than 10 mM, and this fluorescence nanosensor was also successfully used to sense the chloride ion in living cells. PMID- 25135185 TI - Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population. AB - Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using >=140/>=90, >=130/>=80, >=135/>=85, and >=120/>=70 mm Hg as hypertension thresholds for conventional, 24 hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice. PMID- 25135189 TI - TRPV-ing up pain for a long life. PMID- 25135190 TI - New therapeutic options for anxiety and mood disorders. PMID- 25135188 TI - Mapping of the chromosomal amplification 1p21-22 in bladder cancer. AB - BACKGROUND: The aim of the study was to characterize a recurrent amplification at chromosomal region 1p21-22 in bladder cancer. METHODS: ArrayCGH (aCGH) was performed to identify DNA copy number variations in 7 clinical samples and 6 bladder cancer cell lines. FISH was used to map the amplicon at 1p21-22 in the cell lines. Gene expression microarrays and qRT-PCR were used to study the expression of putative target genes in the region. RESULTS: aCGH identified an amplification at 1p21-22 in 10/13 (77%) samples. The minimal region of the amplification was mapped to a region of about 1 Mb in size, containing a total of 11 known genes. The highest amplification was found in SCaBER squamous cell carcinoma cell line. Four genes, TMED5, DR1, RPL5 and EVI5, showed significant overexpression in the SCaBER cell line compared to all the other samples tested. Oncomine database analysis revealed upregulation of DR1 in superficial and infiltrating bladder cancer samples, compared to normal bladder. CONCLUSIONS: In conclusions, we have identified and mapped chromosomal amplification at 1p21-22 in bladder cancer as well as studied the expression of the genes in the region. DR1 was found to be significantly overexpressed in the SCaBER, which is a model of squamous cell carcinoma. However, the overexpression was found also in a published clinical sample cohort of superficial and infiltrating bladder cancers. Further studies with more clinical material are needed to investigate the role of the amplification at 1p21-22. PMID- 25135192 TI - Test-retest reliability of second lactate turnpoint using two different criteria in competitive cyclists. AB - The aim of this study was to determine the relative and absolute reliability of second lactate turnpoint using fixed and individual blood lactate method in competitive cyclists. Twenty-eight male, well-trained cyclists (30.2 +/- 10.1 years, 72.0 +/- 7.4 kg, 177.3 +/- 4.7 cm) were recruited to participate in this study. Cyclists completed two incremental cycling tests to exhaustion over a period of 7 days to determine their peak power output, maximal oxygen uptake, maximal heart rate, maximal blood lactate concentration and two lactate turnpoint criteria. The fixed blood concentration criterion (3.5 mM) and an individual criterion were assessed by a lactate-power curve, considering power output, heart rate and oxygen uptake. The main finding of this study was that both lactate turnpoint criteria showed identical low within-subject variation for power output (2.8% coefficient of variation). High values for test-retest correlations ranging from r = 0.70 to r = 0.94 were found for all variables in both threshold criteria. In conclusion, the individual and fixed method to determine the second lactate turnpoint showed similar high absolute and relative reliability in competitive cyclists. PMID- 25135191 TI - Long-term effects of a collaborative care intervention on process of care in family practices in Germany: a 24-month follow-up study of a cluster randomized controlled trial. AB - OBJECTIVE: The aims of this study were (1) to assess the long-term effects of a collaborative care intervention for patients with depression on process of care outcomes, and (2) to describe whether case management was continued after the end of the original one-year intervention. METHODS: This 24-month follow-up of a randomized controlled trial took place 12 months after the end of the 1-year intervention. Data collection occurred by means of self-rating questionnaires and from medical records. We calculated linear mixed and logistic generalized estimating equation models. RESULTS: Of the 626 patients included at baseline, 439 (70.1%) participated in this follow-up. Intervention recipients gave higher ratings than control recipients in terms of mean overall Patient Assessment of Chronic Illness Care (PACIC) scores (3.12 vs. 2.86; P = .019), but no difference was found in medication adherence (mean Morisky score 2.59 vs. 2.65, P = .56), prescribed antidepressant medications (60.2% vs. 55.1%; P = .25), visits to the family physician (15.96 vs. 14.46, P = .58) or mental health specialist (3.01 vs. 2.94, P = .94) over the 12 month follow-up period. Case management was continued for 47 (22.5%) selected intervention patients after the original intervention had ended. CONCLUSION: At 24 months, intervention and control recipients had different PACIC ratings, but other process of care outcomes did not differ. PRACTICE IMPLICATIONS: The main effects of the intervention are apparent at 12 months. PMID- 25135193 TI - Mitochondrial dysfunction mediated by cytoplasmic acidification results in pollen tube growth cessation in Pyrus pyrifolia. AB - The length of pollen tubes grown in synthetic media is normally shorter than those grown in vivo. However, the mechanism(s) underlying the cessation of pollen tube growth under culture conditions remain(s) largely unknown. Here, we report a previously unknown correlation between vacuolar function and the cell's ability to sustain mitochondrial functions in pear pollen tubes. The pear pollen tubes in vitro grew slowly after 15 hours post-cultured (HPC) and nearly ceased growth at 18 HPC. There was increased malondialdehyde content and membrane ion leakage at 15 HPC compared with 12 HPC. Furthermore, cytoplasmic acidification mainly mediated by decreased vacuolar H(+)-ATPase [V-ATPase, Enzyme Commission (EC) 3.6.1.3] activity was observed in pollen tubes after 15 HPC, and this further resulted in mitochondrial dysfunction, including mitochondrial structure disruption, mitochondrial membrane potential collapse and decreases in both oxygen consumption and ATP production. Our findings suggest that vacuoles and mitochondria intimately linked in regulating pollen tube elongation. PMID- 25135194 TI - The use of research evidence on patient preferences in health care decision making: issues, controversies and moving forward. AB - Patient preferences are increasingly considered important in health care decision making. The consideration of patient preferences is mostly put into practice by giving patients a seat at the decision-making table, instead of using research evidence on patient preferences. The consideration of research evidence on patient preferences is justified and relevant for several reasons. The current limited use of this type of evidence suggests, however, that barriers for its use exist. This paper provides an overview of the issues and controversies related to the use of research evidence on patient preferences. Furthermore, an agenda for research and practice is proposed. The paper focuses on two decision contexts, clinical practice guideline development and reimbursement decision-making. PMID- 25135187 TI - The bacterial translation stress response. AB - Throughout their life, bacteria need to sense and respond to environmental stress. Thus, such stress responses can require dramatic cellular reprogramming, both at the transcriptional as well as the translational level. This review focuses on the protein factors that interact with the bacterial translational apparatus to respond to and cope with different types of environmental stress. For example, the stringent factor RelA interacts with the ribosome to generate ppGpp under nutrient deprivation, whereas a variety of factors have been identified that bind to the ribosome under unfavorable growth conditions to shut down (RelE, pY, RMF, HPF and EttA) or re-program (MazF, EF4 and BipA) translation. Additional factors have been identified that rescue ribosomes stalled due to stress-induced mRNA truncation (tmRNA, ArfA, ArfB), translation of unfavorable protein sequences (EF-P), heat shock-induced subunit dissociation (Hsp15), or antibiotic inhibition (TetM, FusB). Understanding the mechanism of how the bacterial cell responds to stress will not only provide fundamental insight into translation regulation, but will also be an important step to identifying new targets for the development of novel antimicrobial agents. PMID- 25135195 TI - Reconsolidation of a well-learned instrumental memory. AB - Once consolidated, memories are dynamic entities that go through phases of instability in order to be updated with new information, via a process of reconsolidation. The phenomenon of reconsolidation has been demonstrated in a wide variety of experimental paradigms. However, the memories underpinning instrumental behaviors are currently not believed to reconsolidate. We show that well-learned lever pressing in rats does undergo reconsolidation, which can be disrupted by systemic administration of the noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo[a,d]cyclohepten 5,10-imine maleate (MK-801) when administered prior to a switch to a variable, but not fixed, ratio schedule. Disruption of reconsolidation resulted in a reduction in long-term lever pressing performance and diminished the sensitivity of behavior to contingency change. Further investigation demonstrated that expression of the reconsolidation impairment was not affected by outcome value, implying a deficit in a stimulus-response (S-R) process. The ability to disrupt the performance of well-learned instrumental behaviors is potentially of great importance in the development of reconsolidation-based clinical treatments for conditions that involve compulsive seeking behaviors. PMID- 25135196 TI - Protein degradation by ubiquitin-proteasome system in formation and labilization of contextual conditioning memory. AB - The ubiquitin-proteasome system (UPS) of protein degradation has been evaluated in different forms of neural plasticity and memory. The role of UPS in such processes is controversial. Several results support the idea that the activation of this system in memory consolidation is necessary to overcome negative constrains for plasticity. In this case, the inhibition of the UPS during consolidation impairs memory. Similar results were reported for memory reconsolidation. However, in other cases, the inhibition of UPS had no effect on memory consolidation and reconsolidation but impedes the amnesic action of protein synthesis inhibition after retrieval. The last finding suggests a specific action of the UPS inhibitor on memory labilization. However, another interpretation is possible in terms of the synthesis/degradation balance of positive and negative elements in neural plasticity, as was found in the case of long-term potentiation. To evaluate these alternative interpretations, other reconsolidation-interfering drugs than translation inhibitors should be tested. Here we analyzed initially the UPS inhibitor effect in contextual conditioning in crabs. We found that UPS inhibition during consolidation impaired long-term memory. In contrast, UPS inhibition did not affect memory reconsolidation after contextual retrieval but, in fact, impeded memory labilization, blocking the action of drugs that does not affect directly the protein synthesis. To extend these finding to vertebrates, we performed similar experiments in contextual fear memory in mice. We found that the UPS inhibitor in hippocampus affected memory consolidation and blocked memory labilization after retrieval. These findings exclude alternative interpretations to the requirement of UPS in memory labilization and give evidence of this mechanism in both vertebrates and invertebrates. PMID- 25135199 TI - Racial disparity in metastatic renal cell cancer: the pharmaco-anthropology of sunitinib. PMID- 25135200 TI - Serious hepatic complications of selective internal radiation therapy with yttrium-90 microsphere radioembolization for unresectable liver tumors. AB - AIM: Selective internal radiation therapy with yttrium-90 microsphere radioembolization has been used to treat unresectable liver tumors and its acute toxicity has been well described. Subacute and long-term hepatic complications related to radioembolization however may be underreported in the literature. This retrospective study describes the incidence and sequelae of serious hepatic complications in patients who underwent radioembolization for unresectable liver tumors. METHODS: A retrospective review of clinical notes of patients who received radioembolization for unresectable liver tumors from 2001 to 2011 at two Australian institutions was performed to identify those who developed clinically significant hepatic complications. Relevant clinical data were obtained and analyzed to determine their incidence and sequelae. RESULTS: A total of 205 patients were identified, of whom 10 (4.9%) developed serious hepatic complications with 7 (3.4%) attributable to radioembolization-induced liver disease. None had preexisting underlying liver disease or progressive hepatic metastases at the time of developing hepatic complication. The median time to the onset of hepatic complications was 3.5 months (range 1-67 months); six patients had a complete resolution eventually, including one patient who subsequently underwent hepatic metastasectomy safely. Three patients died as a result of fulminant hepatic failure. CONCLUSION: Selective internal radiation therapy with radioembolization was associated with serious hepatic complications with an incidence of 4.9% and a mortality rate of 1.5% in 205 patients from two Australian institutions. The risk of serious hepatic toxicity therefore needs to be discussed when counseling patients regarding this potential treatment option. PMID- 25135197 TI - Safety signals as instrumental reinforcers during free-operant avoidance. AB - Safety signals provide "relief" through predicting the absence of an aversive event. At issue is whether these signals also act as instrumental reinforcers. Four experiments were conducted using a free-operant lever-press avoidance paradigm in which each press avoided shock and was followed by the presentation of a 5-sec auditory safety signal. When given a choice between two levers in Experiment 1, both avoiding shock, rats preferentially responded on the lever that produced the safety signal as feedback, even when footshock was omitted. Following avoidance training with a single lever in Experiment 2, removal of the signal led to a decrease in avoidance responses and an increase in responses during the safety period normally denoted by the signal. These behavioral changes demonstrate the dual conditioned reinforcing and fear inhibiting properties of the safety signal. The associative processes that support the reinforcing properties of a safety signal were tested using a novel revaluation procedure. Prior experience of systemic morphine during safety signal presentations resulted in an increased rate of avoidance responses to produce the safety signal during a drug-free extinction test, a finding not seen with d-amphetamine in Experiment 3. Morphine revaluation of the safety signal was repeated in Experiment 4 followed by a drug-free extinction test in which responses did not produce the signal for the first 10 min of the session. Instrumental avoidance in the absence of the signal was shown to be insensitive to prior signal revaluation, suggesting that the signal reinforces free-operant avoidance behavior through a habit-like mechanism. PMID- 25135198 TI - Understanding functional miRNA-target interactions in vivo by site-specific genome engineering. AB - MicroRNA (miRNA) target recognition is largely dictated by short 'seed' sequences, and single miRNAs therefore have the potential to regulate a large number of genes. Understanding the contribution of specific miRNA-target interactions to the regulation of biological processes in vivo remains challenging. Here we use transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technologies to interrogate the functional relevance of predicted miRNA response elements (MREs) to post-transcriptional silencing in zebrafish and Drosophila. We also demonstrate an effective strategy that uses CRISPR-mediated homology directed repair with short oligonucleotide donors for the assessment of MRE activity in human cells. These methods facilitate analysis of the direct phenotypic consequences resulting from blocking specific miRNA-MRE interactions at any point during development. PMID- 25135201 TI - Epidermal growth factor receptor-tyrosine kinase inhibitors in advanced squamous cell carcinoma of the lung: a meta-analysis. AB - AIM: Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are well established in treating metastatic pulmonary adenocarcinoma, especially patients with activating EGFR mutations. EGFR mutations are rare in pulmonary squamous cell carcinomas (SCCs). There are conflicting data supporting the efficacy of EGFR-TKIs in advanced lung SCC. We analyzed the impact of EGFR-TKIs on progression-free survival (PFS) and overall survival (OS) in unselected patients with lung SCC. METHODS: We searched for randomized controlled trials (RCTs) comparing EGFR-TKIs alone with placebo in patients with metastatic non-small cell lung cancer. RCTs in all settings (front line/maintenance/subsequent) were included. The primary outcome was OS in the SCC population. We used published hazard ratios (HRs), and when unavailable, unpublished data were sought. Pooled estimates of treatment effect on OS and PFS were calculated using the fixed-effects inverse variance weighted method. RESULTS: Eight eligible RCTs were included: 2 first-line, 6 second-line or beyond, evaluating 1781 patients. Data were available for OS in four studies (second-line; N=1420) and for PFS in four studies (3 second-line, 1 first-line; N=788). EGFR-TKIs significantly prolonged OS with a HR of 0.88 (95% confidence interval [CI] 0.78-1.00, P=0.04), and significantly prolonged PFS with a HR of 0.77 (95% CI 0.65-0.92, P=0.004). CONCLUSION: EGFR mutations are rare in lung SCC. However, EGFR-TKIs have a modest therapeutic effect compared to placebo in unselected patients with advanced pulmonary SCC, and can be considered in these patients. EGFR-mutation-independent mechanisms may explain efficacy of EGFR inhibitors in this setting. PMID- 25135204 TI - Knockdown of alphaIIb by RNA degradation by delivering deoxyoligonucleotides piggybacked with control vivo-morpholinos into zebrafish thrombocytes. AB - Morpholino and vivo-morpholino gene knockdown methods have been used to study thrombocyte function in zebrafish. However, a large-scale knockdown of the entire zebrafish genome using these technologies to study thrombocyte function is prohibitively expensive. We have developed an inexpensive gene knockdown method, which uses a hybrid of a control vivo-morpholino and a standard antisense oligonucleotide specific for a gene. This hybrid molecule is able to deliver antisense deoxyoligonucleotides into zebrafish thrombocytes because it piggybacks on a control vivo-morpholino. To validate use of this hybrid molecule in gene knockdowns, we targeted the thrombocyte specific alphaIIb gene with a hybrid of a control vivo-morpholino and an oligonucleotide antisense to alphaIIb mRNA. The use of this piggyback technology resulted in degradation of alphaIIb mRNA and led to thrombocyte functional defect. This piggyback method to knockdown genes is inexpensive since one control vivo-morpholino can be used to target many different genes by making many independent gene-specific oligonucleotide hybrids. Thus, this novel piggyback technology can be utilized for cost-effective large scale knockdowns of genes to study thrombocyte function in zebrafish. PMID- 25135205 TI - The Concerns About Recurrence Questionnaire: validation of a brief measure of fear of cancer recurrence amongst Danish and Australian breast cancer survivors. AB - PURPOSE: Fear of cancer recurrence (FCR) is prevalent amongst survivors, and breast cancer survivors are particularly vulnerable. Currently, there are few well-validated brief measures of FCR and none specific to breast cancer. This manuscript describes the development and initial validation of a new measure of FCR for breast cancer survivors, the Concerns about Recurrence Questionnaire (CARQ), and reports its initial validation in an Australian and Danish population based sample of breast cancer survivors. METHODS: CTT analyses explored scale reliability and validity; Rasch analyses explored model fit statistics, item bias (DIF) and local dependency. Three-item, four-item and five-item versions were considered. RESULTS: Two hundred eighteen Australian women aged 28-45 years diagnosed with early-stage breast cancer (stages 0-2) and 2001 Danish women diagnosed with breast cancer (stages 1-3) aged 26-70 completed the CARQ. Based on the results of both CTT and IRT analyses, the four-item English version of the scale performed best. Although the CTT analyses suggested that the CARQ-4 was reliable and valid in both samples, Rasch analyses identified item bias relative to age, and local dependence which may be remedied by further scale development. CONCLUSIONS: The CARQ-4 English version is currently one of the most rigorously tested brief scales of FCR available. IMPLICATIONS FOR CANCER SURVIVORS: The availability of more valid and reliable brief measures of FCR will help to promote research and screening of FCR amongst cancer survivors. PMID- 25135206 TI - Identifying suicidal symptoms in prostate cancer survivors using brief self report. AB - PURPOSE: Prostate cancer (PC) survivors are at elevated risk for completed suicide even many years post-treatment. Despite this risk, practical and efficient methods for assessing these symptoms have not been established. We sought to determine if suicidal symptoms could be effectively and efficiently identified in a cohort of PC survivors, and whether these men were receptive to emotional health interventions. METHODS: Six hundred fifty-six PC survivors, an average of 5 years post-diagnosis, completed eight self-report items about suicidal symptoms and behavior in the past 7 days, and 12 months, as well as medical utilization and interest in emotional health support. RESULTS: Between 3.6 and 17.9% of PC survivors endorsed a single suicidal ideation item, and denied all other ideation. All survivors who endorsed serious suicidal ideation/behavior also endorsed either passive or active ideation. 58.3% of survivors denied any suicidal symptoms within the past week, but endorsed it within the past year. Most survivors had medical provider contact within the past year and were open to receiving information about emotional health interventions. CONCLUSIONS: Suicidal ideation in PC survivors cannot be accurately evaluated using only a one-item screen, or by inquiring within a single time frame. IMPLICATIONS FOR CANCER SURVIVORS: In both research and clinical settings, the evaluation for suicidal ideation in PC survivors should utilize multiple questions, across several time periods. It is possible to skip queries about serious ideation/behavior if passive or active ideation is denied. Once identified, medical providers should refer these men to psychosocial providers who can offer emotional support. PMID- 25135208 TI - The study of the complexes of nitromedicine with cytochrome c and NO-containing aqueous dosage form in the wound treatment of rats. AB - The interaction of cytochrome c with nitromedicines, such as 5-nitrofural, 5 nitroxoline, metronidazole and sodium nitrite which enables the generation of nitric oxide or nitrosyl complexes in the presence of ascorbic acid or sodium ascorbate in acid medium has been investigated. The pharmaceutical compositions containing cytochrome c and nitromedicine complexes as active substances were studied in the experiments by using rats. It has been shown that positive local and systemic effects were estimated when NO-containing gel was used at burn treatment. These positive effects at the local level are due to a sufficient microcirculation index which indicates intensification of the blood flow in the microvessels in the injured area. These effects at the systemic level provide maintenance of the general heart rhythm and gradual recovery of the vegetative balance which is not observed in the animals of the control group. PMID- 25135207 TI - Barriers to access and minority ethnic carers' satisfaction with social care services in the community: a systematic review of qualitative and quantitative literature. AB - As populations age, the numbers of carers overall and numbers of carers from minority ethnic groups in particular are rising. Evidence suggests that carers from all sections of the community and particularly carers from minority groups often fail to access care services. This may relate to barriers in accessing services and service dissatisfaction. The aim of this systematic review was to identify and summarise minority ethnic carers' perceptions of barriers to accessing community social care services and their satisfaction with these services if accessed. The following databases were searched from their start until July 2013: Social Care Online, Social Policy and Research, Scopus, PsychINFO, HMIC, ASSIA, MEDLINE, Embase, CINAHL Plus and AMED. Thirteen studies met the inclusion criteria. Most investigated either barriers to access or satisfaction levels, although three explored both. Only 4 studies investigated minority ethnic carers' satisfaction with social care, although 12 studies reported perceived barriers to accessing services. Few studies compared minority ethnic carers' perceptions with majority ethnic groups, making it difficult to identify issues specific to minority groups. Most barriers described were potentially relevant to all carers, irrespective of ethnic group. They included attitudinal barriers such as not wanting to involve outsiders or not seeing the need for services and practical barriers such as low awareness of services and service availability. Issues specific to minority ethnic groups included language barriers and concerns about services' cultural or religious appropriateness. Studies investigating satisfaction with services reported a mixture of satisfaction and dissatisfaction. Barriers common to all groups should not be underestimated and a better understanding of the relationship between perceived barriers to accessing services and dissatisfaction with services is needed before the experiences of all carers can be improved. PMID- 25135209 TI - Generation of an rhBMP-2-loaded beta-tricalcium phosphate/hydrogel composite and evaluation of its efficacy on peri-implant bone formation. AB - Dental implant insertion on a site with low bone quality or bone defect should be preceded by a bone graft or artificial bone graft insertion to heal the defect. We generated a beta-tricalcium phosphate (beta-TCP) and poloxamer 407-based hydrogel composite and penetration of the beta-TCP/hydrogel composite into the peri-implant area of bone was evaluated by porous bone block experiments. The maximum penetration depth for porous bone blocks and dense bone blocks were 524 MUm and 464 MUm, respectively. We report the in-vivo performance of a composite of beta-TCP/hydrogel composite as a carrier of recombinant human bone morphogenetic protein (rhBMP-2), implanted into a rabbit tibial defect model. Three holes drilled into each tibia of eight male rabbits were (1) grafted with dental implant fixtures; (2) filled with beta-TCP/hydrogel composite (containing 5 MUg of rhBMP-2), followed by grafting of the dental implant fixtures. Four weeks later, bone-implant contact ratio and peri-implant bone formation were analyzed by radiography, micro-CT and histology of undecalcified specimens. The micro-CT results showed a significantly higher level of trabecular thickness and new bone and peri-implant new bone formation in the experimental treatment compared to the control treatment. Histomorphometry revealed a significantly higher bone-implant contact ratio and peri-implant bone formation with the experimental treatment. The use of beta-TCP/poloxamer 407 hydrogel composite as a carrier of rhBMP-2 significantly promoted new bone formation around the dental implant fixture and it also improved the quality of the new bone formed in the tibial marrow space. PMID- 25135210 TI - Countertransference before Heimann: an historical exploration. AB - Received wisdom on the history of countertransference rests on two assumptions: Freud said little about countertransference, and what he did say focused on its role as an impediment to analytic work; the emergence in the 1950s of a conception of countertransference as a crucial beneficial component of psychoanalysis was revolutionary and innovative. Both assumptions are questionable. Detailed examination of Freud's public and private discussions of countertransference reveals that he recognized much of its potential value, as well as its pitfalls, and suggested that the analyst's contributions should be based on spontaneous affect, measured out consciously. He was aware of the problematic nature of countertransference, calling for a paper on countertransference even while cautioning against its public presentation. His remarks, particularly in letters, taken together with the work of Ferenczi and other early contributors, show that the pre-1950s literature on countertransference prefigured much current debate on the topic. PMID- 25135211 TI - Erik Erikson and his problematic identity. AB - In his psychohistorical biographies of Luther and Gandhi, Erik Erikson proposed that great issues of a particular time and place, as experienced by sensitive and creative individuals who are working to resolve their inner conflicts within these contexts, could find solutions that transcend themselves and yield conceptualizations that transform the world. Although Erikson was able to create a conceptualization of the adolescent task of establishing a coherent identity, one that gave voice to the aspirations and frustrations of the rebellious student movements of the 1960s, he was never able, over his lifetime, to resolve his own identity issues. Was he Dane or German, American or Scandinavian, Jew or Christian or both? His lifelong back-and-forths on this struggle are chronicled. PMID- 25135212 TI - Journal Watch review of Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders. PMID- 25135213 TI - Journal Watch review of oxytocin and reduction of social threat hypersensitivity in women with borderline personality disorder. PMID- 25135214 TI - Journal Watch review of Patient personality and therapist response: an empirical investigation. PMID- 25135215 TI - Transformation of personality: deformation and reformation in confronting death. PMID- 25135216 TI - Detecting protein-protein interactions based on kinase-mediated growth induction of mammalian cells. AB - Detection of protein-protein interactions (PPIs) is important for understanding numerous processes in mammalian cells; however, existing PPI detection methods often give significant background signals. Here, we propose a novel PPI-detection method based on kinase-mediated growth induction of mammalian cells. In this method, target proteins are fused to the intracellular domain of c-kit (c-kit ICD) and expressed in interleukin-3-dependent mammalian cells. The PPI induces dimerization and activation of c-kit ICDs, which leads to cell growth in the absence of interleukin-3. Using this system, we successfully detected the ligand dependent homo-interaction of FKBPF36V and hetero-interaction of FKBP and FRBT2098L, as well as the constitutive interaction between MDM2 and a known peptide inhibitor. Intriguingly, cells expressing high-affinity peptide chimeras are selected from the mixture of the cell populations dominantly expressing low affinity peptide chimeras. These results indicate that this method can detect PPIs with low background levels and is suitable for peptide inhibitor screening. PMID- 25135217 TI - Discovery of novel peptides regulating competence development in Streptococcus mutans. AB - A MarR-like transcriptional repressor (RcrR) and two predicted ABC efflux pumps (RcrPQ) encoded by a single operon were recently shown to be dominant regulators of stress tolerance and development of genetic competence in the oral pathogen Streptococcus mutans. Here, we focused on polar (DeltarcrR-P) and nonpolar (DeltarcrR-NP) rcrR mutants, which are hyper- and nontransformable, respectively, to dissect the mechanisms by which these mutations impact competence. We discovered two open reading frames (ORFs) in the 3' end of the rcrQ gene that encode peptides of 27 and 42 amino acids (aa) which are also dramatically upregulated in the DeltarcrR-NP strain. Deletion of, or start codon mutations in, the ORFs for the peptides in the DeltarcrR-NP background restored competence and sensitivity to competence-stimulating peptide (CSP) to levels seen in the DeltarcrR-P strain. Overexpression of the peptides adversely affected competence development. Importantly, overexpression of mutant derivatives of the ABC exporters that lacked the peptides also resulted in impaired competence. FLAG tagged versions of the peptides could be detected in S. mutans, and FLAG tagging of the peptides impaired their function. The competence phenotypes associated with the various mutations, and with overexpression of the peptides and ABC transporters, were correlated with the levels of ComX protein in cells. Collectively, these studies revealed multiple novel mechanisms for regulation of competence development by the components of the rcrRPQ operon. Given their intimate role in competence and stress tolerance, the rcrRPQ-encoded peptides may prove to be useful targets for therapeutics to diminish the virulence of S. mutans. PMID- 25135218 TI - HilD induces expression of Salmonella pathogenicity island 2 genes by displacing the global negative regulator H-NS from ssrAB. AB - Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) have essential roles in the pathogenesis of Salmonella enterica. Previously, we reported transcriptional cross talk between SPI-1 and SPI-2 when the SPI-1 regulator HilD induces expression of the SsrA/B two-component system, the central positive regulator of SPI-2, during the growth of Salmonella to late stationary phase in LB rich medium. Here, we further define the mechanism of the HilD-mediated expression of ssrAB. Expression analysis of cat transcriptional fusions containing different regions of ssrAB revealed the presence of negative regulatory sequences located downstream of the ssrAB promoter. In the absence of these negative cis elements, ssrAB was expressed in a HilD-independent manner and was no longer repressed by the global regulator H-NS. Consistently, when the activity of H-NS was inactivated, the expression of ssrAB also became independent of HilD. Furthermore, electrophoretic mobility shift assays showed that both HilD and H-NS bind to the ssrAB region containing the repressing sequences. Moreover, HilD was able to displace H-NS bound to this region, whereas H-NS did not displace HilD. Our results support a model indicating that HilD displaces H-NS from a region downstream of the promoter of ssrAB by binding to sites overlapping or close to those sites bound by H-NS, which leads to the expression of ssrAB. Although the role of HilD as an antagonist of H-NS has been reported before for other genes, this is the first study showing that HilD is able to effectively displace H-NS from the promoter of one of its target genes. PMID- 25135219 TI - The biochemical value of urinary metalloproteinases 3 and 9 in diagnosis and prognosis of bladder cancer in Egypt. AB - BACKGROUND: Matrix metalloproteinases (MMPs) have long been associated with cancer-cell invasion and metastasis. Few studies are available that describe this association with bladder cancer either related or unrelated to schistosoma infection.Evaluating the urinary levels of MMP3 and MMP9 as diagnostic and prognostic biomarkers in different stages of schistosomal and non schistosomal bladder cancer was the aim of the present study.Urine samples were collected from 70 patients with schistosomal and non schistosomal bladder cancer at early and advanced stages and also from 12 healthy volunteers as controls. Urinary levels of MMP-3 and MMP-9 was measured by ELISA technique. Sensitivity and specificity of both markers were determined. RESULTS: Urinary levels of both MMP-3 and MMP-9 were significantly elevated in all bladder cancer patients compared with controls. MMP-3 started to elevate in early stages of schistosomal bladder cancer ( 0.173 ng/ml) and non-schistosomal bladder cancer patients (0.308 ng/ml) compared to control (0.016 ng/ml) and remained elevated in advanced stages (0.166, 0.235 ng/ml) of both types of bladder cancer patients. In contrast, MMP-9 showed a significant elevation in advanced stages only of both schistosomal and non schistosomal bladder cancer patients (10.33, 21.22 ng/ml) compared to control (0.409 ng/ml) and this elevation of both markers was much higher in non schistosomal bladder cancer. Both Metalloproteinases were specific for the diagnosis of the disease but MMP-3 was more sensitive and this sensitivity was evident in the early stage (84.85% for MMP3, 27.28% for MMP9). CONCLUSIONS: MMP3 may be the recommended urinary metalloproteinases as early diagnostic biomarker in the early stages of both types of bladder cancer although both MMP9 and MMP3 can be used in the diagnosis of advanced stages. Further studies are required on large number of urine samples to confirm these results. PMID- 25135220 TI - beta6 integrin induces the expression of metalloproteinase-3 and metalloproteinase-9 in colon cancer cells via ERK-ETS1 pathway. AB - We previously reported that beta6 integrin played an important role in the progression of colon cancer. In this study, we demonstrated that beta6 integrin induced the expression of MMP-3/MMP-9 and the invasion of colon cancer cells. Moreover, that function was abolished by the inhibition of ERK/MAPK pathways or knockdown of ETS1, an important transcription factor of MMP genes. Here, we showed that beta6 induced phosphorylation of ETS1 via the ERK/MAPK pathways, through which the MMP-3/MMP-9 promoters were stimulated, thereby leading to the up-regulation of MMP-3/MMP-9, and subsequent the invasion of colon cancer cells. PMID- 25135221 TI - A novel beta-catenin signaling pathway activated by IL-1beta leads to the onset of epithelial-mesenchymal transition in breast cancer cells. AB - Interleukin 1beta has been associated with tumor development, invasiveness and metastasis in various types of cancer. However, the molecular mechanisms underlying this association have not been clearly elucidated. The present study is the first to show, in breast cancer cells, that an IL-1beta/IL-1RI/beta catenin signaling pathway induces beta-catenin accumulation due to GSK3beta inactivation by Akt phosphorylation. Translocation to the nucleus of accumulated beta-catenin and formation of the TCF/Lef/beta-catenin complex induce sequential expression of c-MYC, CCDN1, SNAIL1 and MMP2, leading to up-regulation of proliferation, migration and invasion; all of the processes shown to be required, in cancerous cells, to initiate transition from a non-invading to an invasive phenotype. PMID- 25135222 TI - TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1 transcription in human lung adenocarcinoma. AB - Aberrant epidermal growth factor (EGF)-dependent signaling plays a key role in the progression of human carcinomas. We found that TIP30, a tumor suppressor protein, translocated into the nucleus of human lung adenocarcinoma cells following EGF treatment, and the selective inhibitors of EGFR signaling pathways blocked this effect. Chromatin immunoprecipitation assays revealed that TIP30 negatively regulated EGF-dependent transcriptional activation of CCND1 through a HDAC1-dependent mechanism. In lung adenocarcinoma patients, the level of nuclear TIP30 was inversely correlated with that of EGFR and cyclin D1. These findings suggest that nuclear TIP30-induced downregulation of cyclin D1 transcription antagonizes EGFR signaling and suppresses tumorigenesis. PMID- 25135223 TI - Strategy to enhance the anticancer efficacy of X-ray radiotherapy in melanoma cells by platinum complexes, the role of ROS-mediated signaling pathways. AB - Radiotherapy plays an important role in treatment of cancers with low toxicity to the surrounding normal tissues. However, it still fails to eradicate hypoxic tumors due to the occurrence of radioresistance. Therefore, the search for new radiation sensitizers is of great significance. Platinum (Pt) complexes have been identified as potential radiation sensitizers to increase the sensitivity of cancer cells to radiotherapy. In the present study, we have synthesized four Pt complexes containing (2 - benzimidazole [4, 5-f] - [1, 10] phenanthroline) ligand and found that they could effectively enhance the X-ray-induced growth inhibition against A375 human melanoma cells through induction of G2/M cell cycle arrest. In contrast, they showed much lower cytotoxicity toward human normal cells. The complexes also dramatically inhibited the TrxR activity and caused intracellular ROS overproduction, due to the Auger electron effect of heavy metal element under X-ray radiation. Excessive ROS triggered DNA damage and activated downstream signaling pathways, including the phosphorylation of p53 and p38MAPK, and down regulation of phosphorylated AKT and ERK, finally resulted in increase of radiosensitivity and inhibition of tumor reproduction. Taken together, our results suggest that the synthetic Pt complexes could be further developed as sensitizers of X-ray radiotherapy. PMID- 25135224 TI - Postoperative changes in amniotic membrane as a carrier for allogeneic cultured limbal epithelial transplantation. AB - PURPOSE: To investigate the morphologic changes and outcomes of the amniotic membrane as a carrier for allogeneic cultivated limbal epithelial transplantation. DESIGN: Prospective, noncomparative, interventional study. METHODS: A total of 16 eyes receiving allogeneic cultivated limbal epithelial transplantation with amniotic membrane as a carrier were enrolled. Morphologic changes in the amniotic membrane were observed by confocal microscopy and RTVue optical coherence tomography. The paired t test was employed to compare the mean best corrected visual acuity (BCVA) and corneal stromal thickness. RESULTS: Of the 16 eyes, 12 had stable ocular surfaces (group A), while the other 4 eyes had failed surgeries due to immune rejection (group B). Confocal microscopy showed residual amniotic membrane tissues in 8 eyes in group A at 1 year. However, the amniotic membrane was not detected in group B at 8-10 months. RTVue optical coherence tomography showed discontinuous amniotic membrane tissues in all eyes in group A at 1 year, while highly reflective opacity was seen in the corneal stroma in group B. There were no statistically significant differences in mean BCVA and corneal stromal thickness in group A at 1 month and 1 year after transplantation (P > 0.05), but the mean BCVA showed a statistically significant difference at 1 month and after the disappearance of the amniotic membrane in group B (P < 0.05). CONCLUSIONS: For eyes with stable ocular surfaces after cultivated limbal epithelial transplantation, the amniotic membrane can be present in the cornea for at least 1 year, with no impact on visual acuity or corneal stromal thickness. Chronic inflammation and neovascularization on the ocular surface may accelerate the disappearance of the amniotic membrane. PMID- 25135225 TI - Recurrent 8q13.2-13.3 microdeletions associated with branchio-oto-renal syndrome are mediated by human endogenous retroviral (HERV) sequence blocks. AB - BACKGROUND: Human endogenous retroviral (HERV) sequences are the remnants of ancient retroviral infection and comprise approximately 8% of the human genome. The high abundance and interspersed nature of homologous HERV sequences make them ideal substrates for genomic rearrangements. A role for HERV sequences in mediating human disease-associated rearrangement has been reported but is likely currently underappreciated. METHODS AND RESULTS: In the present study, two independent de novo 8q13.2-13.3 microdeletion events were identified in patients with clinical features of Branchio-Oto-Renal (BOR) syndrome. Nucleotide-level mapping demonstrated the identical breakpoints, suggesting a recurrent microdeletion including multiple genes such as EYA1, SULF1, and SLCO5A1, which is mediated by HERV1 homologous sequences. CONCLUSIONS: These findings raise the potential that HERV sequences may more commonly underlie recombination of dosage sensitive regions associated with recurrent syndromes. PMID- 25135226 TI - Developing and evaluating interventions that are applicable and relevant to inpatients and those who care for them; a multiphase, pragmatic action research approach. AB - BACKGROUND: Randomised controlled trials may be of limited use to evaluate the multidisciplinary and multimodal interventions required to effectively treat complex patients in routine clinical practice; pragmatic action research approaches may provide a suitable alternative. METHODS: A multiphase, pragmatic, action research based approach was developed to identify and overcome barriers to nutritional care in patients admitted to a metropolitan hospital hip-fracture unit. RESULTS: Four sequential action research cycles built upon baseline data including 614 acute hip-fracture inpatients and 30 purposefully sampled clinicians. Reports from Phase I identified barriers to nutrition screening and assessment. Phase II reported post-fracture protein-energy intakes and intake barriers. Phase III built on earlier results; an explanatory mixed-methods study expanded and explored additional barriers and facilitators to nutritional care. Subsequent changes to routine clinical practice were developed and implemented by the treating team between Phase III and IV. These were implemented as a new multidisciplinary, multimodal nutritional model of care. A quasi-experimental controlled, 'before-and-after' study was then used to compare the new model of care with an individualised nutritional care model. Engagement of the multidisciplinary team in a multiphase, pragmatic action research intervention doubled energy and protein intakes, tripled return home discharge rates, and effected a 75% reduction in nutritional deterioration during admission in a reflective cohort of hip-fracture inpatients. CONCLUSIONS: This approach allowed research to be conducted as part of routine clinical practice, captured a more representative patient cohort than previously reported studies, and facilitated exploration of barriers and engagement of the multidisciplinary healthcare workers to identify and implement practical solutions. This study demonstrates substantially different findings to those previously reported, and is the first to demonstrate that multidisciplinary, multimodal nutrition care reduces intake barriers, delivers a higher proportional increase in protein and energy intake compared with baseline than other published intervention studies, and improves patient outcomes when compared with individualised nutrition care. The findings are considered highly relevant to clinical practice and have high translation validity. The authors strongly encourage the development of similar study designs to investigate complex health problems in elderly, multi-morbid patient populations as a way to evaluate and change clinical practice. PMID- 25135227 TI - Antenatal hepatitis B in a large teaching NHS Trust - implications for future care. AB - OBJECTIVES: To establish the workload expected as a result of introducing antenatal antivirals for the prevention of vertical transmission of hepatitis B virus. METHODS: Retrospective review of all HBsAg-positive women and their infants, between 2005 and 2011, in a large (population 1 million) teaching NHS Trust in Leicester, UK, a highly ethnically diverse city. RESULTS: 7% of pregnancies occurred in women who were taking, or would now be recommended to take, antenatal antivirals. 176 infants were born to 140 HBsAg-positive women through 172 pregnancies (mean 29 pregnancies/year). Two (1.1%) were vertically infected, including one born to a mother with HBeAg(-)/HBeAb(+) disease and HBV viral load 2 million IU/ml who would not currently be recommended for antenatal antivirals. 81.1% infants completed all HBV vaccinations; 79.5% completed serology testing. 96.4% women were referred to the hepatitis clinic, but 30% disengaged from clinic follow-up, with no significant difference between ethnic groups in terms of maternal disengagement, or failure to complete infant vaccinations or serology testing. CONCLUSIONS: Only a small percentage of HBsAg positive women are likely to meet the newly published criteria for antenatal anti viral treatment. Strengthened community engagement across multiple ethnic groups is of paramount importance to improve maternal and infant outcomes. PMID- 25135228 TI - Wishful thinking blurs interpretation of AES data in a high endemic region of India. PMID- 25135229 TI - Prevalence, incidence and predictors of anal high-risk HPV infections and cytological abnormalities in HIV-infected individuals. AB - OBJECTIVES: Our purpose was to investigate prevalence, incidence and risk factors of anal high risk-HPV infections and cytological abnormalities in HIV-positive individuals. METHODS: A cohort of consecutively enrolled HIV-positive patients underwent, at baseline visit, a sexual behaviors questionnaire, anoscopy, HPV testing and cytological examination. Hybridization and multiplex-PCR were used for DNA detection and typing; HPV E6-E7 mRNA expression was analyzed in HR-HPV+ patients. Logistic regression was used to assess predictors of HR-HPV infection and anal dysplasia. RESULTS: 233 HIV-infected patients were enrolled (81% males, median age 44 years). HR-HPV was detected in 144 anal swabs and showed a positive association with CDC stage C and a negative association with a higher CD4 count and the use of a NNRTI-based antiretroviral regimen. HR-HPV DNA detection and anal warts at baseline were associated to cytological abnormalities; a detectable HIV-RNA independently predicted new onset anal dysplasia at follow-up (incidence 15.4 per 100 patients-year). Incidence of new HR-HPV infection was 44.2 per 100 patients-year. CONCLUSIONS: The relevance of screening for anal dysplasia in HIV+ patients is emphasized, especially in those with detectable plasma HIV-RNA, anal HR-HPV infection or compromised immunological status. PMID- 25135230 TI - Risk of tuberculosis among healthcare workers in an intermediate-burden country: a nationwide population study. AB - OBJECTIVE: The potential association between healthcare workers (HCWs) and the risk of clinically active tuberculosis (TB) in countries with intermediate TB burdens remains unclear. METHODS: A nationwide, population-based cohort study was performed by using Taiwan National Health Insurance Database during 2000-2010. We included HCWs and non-HCWs without history of tuberculosis matched at a 1:1 ratio according to age, sex, monthly income, underlying comorbidities, and concomitant medications. All subjects were followed from the date of enrollment until TB occurrence, death, or 31 December 2010. RESULTS: The study population comprised 11,811 healthcare workers and 11,811 matched subjects. 62 HCWs and 38 control subjects developed TB during a median follow-up period of 9.4 years. The incidence of TB was higher among HCWs than among matched subjects (61.08 vs. 37.81 per 100,000 person-years). The risk of TB was also greater among HCWs (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.08-2.43), particularly for pulmonary TB in comparison with extrapulmonary TB (aHR, 1.56; 95% CI, 1.02-2.39). Among different job categories of HCWs, we found that only nurses had a significantly increased risk of developing TB (aHR, 2.55; 95% CI, 1.37-4.72) compared to the matched cohort. CONCLUSIONS: HCWs are associated independently with a higher risk of developing TB in this intermediate-burden country. Therefore, the importance of TB surveillance among HCWs should be emphasized. PMID- 25135231 TI - Severe fever with thrombocytopenia syndrome bunyavirus-related human encephalitis. AB - BACKGROUND: Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus. Until recently, SFTSV-associated encephalitis remained largely uninvestigated. METHODS: We made clinical investigation on SFTS patients who experienced encephalitis in one reference hospital in Henan Province from 2011 to 2013 to identify the risk factors for encephalitis occurrence and their fatal outcome development. RESULTS: Altogether 538 SFTS patients were included and 19.1% of them developed encephalitis. Fatal outcome occurred in 44.7% of the encephalitis patients. The risk factors associated with encephalitis occurrence and death included older age, longer delay between disease onset and hospital admission, pre-existing diabetes and myalgias, as well as the laboratory evaluations of higher virus load on admission, decreased WBC, PLT count, lymphocyte percentage and ALB, elevated neutrophils percentage, AST, ALT, LDH, CK, ALP, GGT, BUN and CREA. These parameters could be used as potential predictors referring to severe SFTS cases. One SFTSV strain was isolated from cerebrospinal fluid sample. Cytokine/chemokine assay revealed that blood EOTAXIN, IFN-gamma, IL-15, IL-6, IP-10, TNF-alpha were remarkably elevated before clinical deterioration in the confirmed encephalitis patient. CONCLUSIONS: SFTSV is capable of infecting the central nervous system and screening for SFTSV in encephalitis of unknown reason should be performed in SFTS endemic regions. The encephalitis occurrence and fatal outcome could be potentially predicted by clinical and laboratory evaluations. PMID- 25135232 TI - Renal and visceral protection in thoracoabdominal aortic surgery. AB - OBJECTIVES: Open thoracoabdominal aortic aneurysm (TAAA) repair traditionally carries substantial perioperative morbidity and mortality, primarily from distal aortic ischemia. Advances in surgical techniques, adjuncts, and strategies have greatly improved outcomes. METHODS: We analyzed outcomes of 1267 open consecutive TAAA repairs between January 2005 and September 2013. We provided cold crystalloid renal perfusion whenever the renal ostia were accessible; according to extent of repair, we selectively used left heart bypass and provided isothermic blood to the celiac axis and superior mesenteric artery. Repair was extensive (Crawford extent I and II) in 717 cases (57%). Left heart bypass was used in 645 (51%) cases, cold crystalloid renal perfusion in 987 (78%), and isothermic visceral perfusion in 318 (25%). Additional patient-specific surgical adjuncts included endarterectomy of renal or visceral vessels, open stent placement within these vessels, or use of both techniques; at least one was used in 447 repairs (35%). RESULTS: Thirty-day survival was 95% (1198/1267); overall operative mortality was 8% (104/1267). Acute renal dysfunction occurred in 155 (12%), renal failure requiring hemodialysis at hospital discharge in 84 (7%), and bowel ischemia in 9 (<1%). Extent II and III TAAA repairs carried the highest risks of postoperative renal dysfunction and renal failure requiring hemodialysis at hospital discharge. CONCLUSIONS: Contemporary protective strategies allow open TAAA repair with substantially fewer renal and visceral ischemic complications. Although bowel ischemia is uncommon, renal failure remains a concern, especially in extent II and extent III TAAA repairs. Additional studies are needed to identify and improve renal protection strategies. PMID- 25135233 TI - Persistent fenestration may be a marker for physiologic intolerance after Fontan completion. AB - BACKGROUND: We sought to evaluate the medium-term implications of fenestration status. METHODS: Between 1994 and 2012, 326 patients received an extracardiac Fontan (hospital mortality n = 6, 1.8%). A fenestration was routinely created (n = 306, 94%) unless there was technical difficulty. Three hundred patients discharged with an open fenestration were included. The primary end points were death and Fontan failure. Secondary outcomes were Fontan complications such as venovenous collaterals, protein-losing enteropathy, pacemaker requirement, and arrhythmias. RESULTS: The fenestration was closed in 260 patients: 185 as a catheter intervention (62%) and 75 (25%) spontaneously. Forty patients (13%) had the fenestration open at a median follow-up period of 5.05 years. Of these patients, catheter-based closure failed in 10 (3%). There was no statistically significant difference in pre-Fontan hemodynamic parameters, such as pulmonary artery pressure and pulmonary vascular resistance between the patients with open fenestration and the ones with closed fenestration. Patients with an open fenestration had significantly more late deaths (P < .001), Fontan failure (P = .021), and Fontan complications (P = .011) compared with those with a closed fenestration. Multivariable Cox regression revealed open fenestration (P < .001) and indeterminate ventricular morphology (P = .002) as risk factors for death/Fontan failure, and ventricular dysfunction (P = .014) and open fenestration (P = .009) as risk factors for Fontan complications. CONCLUSIONS: Persistent fenestration was a marker for physiologic intolerance as noted by increased rates of mortality and a higher incidence of Fontan failure/complications. The specificity of pre-Fontan physiologic data for fenestration status may not have the fidelity needed for long-term care and thus, the consequences of decision making regarding fenestration status may not be determined until well after the operation. PMID- 25135234 TI - Surgery of postinfarction ventricular septal rupture: the effect of David infarct exclusion versus Daggett direct septal closure on early and late outcomes. AB - OBJECTIVE: David infarct exclusion and Daggett direct septal closure are alternative techniques to repair postinfarction ventricular septal rupture. The aim of the present study was to compare the 2 methods with regard to postoperative morbidity, 30-day mortality, and long-term survival. METHODS: From May 1981 to December 2010, 110 patients underwent surgery for postinfarction ventricular septal rupture. Data were collected on the clinical, angiographic, and echocardiographic findings, operative procedures, early morbidity, and survival time. The epidemiologic design was of an exposed (David infarct exclusion, n = 42) versus a nonexposed (Daggett direct closure, n = 68) cohort with 3 endpoints: postoperative morbidity, 30-day mortality, and long-term survival. The crude effect of the repair technique versus the endpoint was estimated using univariate statistics. Stratification analysis using the Mantel Haenszel method was done to quantify the confounders and pinpoint the effect modifiers. Adjustment for confounders was performed using logistic regression and Cox regression analysis, and with propensity score stratification statistics. Survival curves were analyzed using the Breslow test and log-rank test. RESULTS: The surgical technique had no influence on postoperative morbidity. The 30-day mortality was 16.7% in the David group and 48.5% in the Daggett group (P = .000). Long-term survival was greater after David than after Daggett, with 5- and 10 year survival of 69% versus 38% and 48% versus 27%, respectively (P = .004). Total coronary revascularization improved survival more in the David than in the Daggett group. CONCLUSIONS: David infarct exclusion was superior to Daggett direct septal closure for early and late survival after surgery for postinfarction ventricular septal rupture. Total coronary revascularization improved survival more in the David than in the Daggett group. PMID- 25135235 TI - Acute Risk Change for Cardiothoracic Admissions to Intensive Care (ARCTIC index): a new measure of quality in cardiac surgery. AB - BACKGROUND: Quality of cardiac surgical care may vary between institutions. Mortality is low and large numbers are required to discriminate between hospitals. Measures other than mortality may provide better comparisons. OBJECTIVES: To develop and assess the Acute Risk Change for Cardiothoracic Admissions to Intensive Care (ARCTIC) index, a new performance measure for cardiothoracic admissions to intensive care units (ICUs). METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons database and Australian and New Zealand Intensive Care Society Adult Patient Database were linked. Logistic regression was used to generate a predicted risk of death first from preoperative data using the previously validated Allprocscore and second on admission to an ICU using Acute Physiology and Chronic Health Evaluation III score. Change in risk as a percentage (ARCTIC) was calculated for each patient. The validity of ARCTIC as a marker of quality was assessed by comparison with intraoperative variables and postoperative morbidity markers. RESULTS: Sixteen thousand six hundred eighty-seven patients at 21 hospitals from 2008 to 2011 were matched. An increase in ARCTIC score was associated with prolonged cardiopulmonary bypass time (P = .001), intraoperative blood product transfusion (P < .001), reoperation (P < .0001), postoperative renal failure (P < .0001), prolonged ventilation (P < .0001), and stroke (P = .001). CONCLUSIONS: The ARCTIC index is associated with known markers of perioperative performance and postoperative morbidity. It may be used as an overall marker of quality for cardiac surgery. Further work is required to assess ARCTIC as a method to discriminate between cardiac surgical units. PMID- 25135236 TI - Bayesian stopping guidelines for heart valve premarket approval studies. AB - OBJECTIVES: The Data Monitoring Committee (DMC) for the premarket approval (PMA) study of a new heart valve prosthesis convenes periodically to review the accumulating results of the study, and determines, among other things, whether there is enough concern with safety to stop the study. Their deliberations are largely subjective, based on their combined experience and expertise, but an objective aid to evaluating complication rates, usually called a stopping rule, is desirable. METHODS: The US Food and Drug Administration has designated objective performance criteria (OPC) for 7 heart valve complications. At the end of the PMA study, when approximately 800 patient-years have been accumulated, the complication rates must compare favorably with the OPC. Given the results to date at an interim review of the data, we use a Bayesian approach to compute the probability of passing the OPC test by the end of study. RESULTS: We provide a method that the DMC can use to predict the probability of passing the OPC test for each complication, and a graphical aid for each number of events, observed at 100 patient-year intervals. CONCLUSIONS: Although the DMC ultimately uses combined experience and expertise to make the decision to stop a PMA valve study, we have provided an objective assessment of the probability of the valve ultimately passing the OPC test to aid in making that decision. PMID- 25135237 TI - Are preoperative B-type natriuretic peptide levels associated with outcome after pulmonary artery banding and the double switch operation in patients with congenitally corrected transposition of the great arteries: a pilot study. PMID- 25135238 TI - The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study. AB - BACKGROUND: Fluorouracil and cisplatin have been used most frequently as neoadjuvant therapy for esophageal cancer. Both drugs are believed to act via a p53-dependent apoptosis pathway. The TP53 gene is frequently mutated in esophageal cancer. OBJECTIVE: To test the value of TP53 as a biomarker prognosing outcome in patients with neoadjuvantly treated esophageal cancer. PATIENTS AND METHODS: The investigation included 36 patients with primary operable esophageal cancer who were treated neoadjuvantly with cisplatin and fluorouracil. The TP53 genotype was assessed from paraffin-embedded diagnostic tumor biopsies using a standardized gene-specific TP53 sequencing protocol (mark53 kit; mark53 Ltd, Vienna, Austria). RESULTS: Mutations in the TP53 gene were present in 50% of tumors. Two-year overall survival rates were 55.6% in patients with a normal TP53 marker status, compared with 16.7% in those with a mutant TP53 gene. In patients with normal TP53, neoadjuvant treatment resulted in significant advantages in terms of tumor-associated survival (P=.0049) and overall survival (P=.0304) compared with those with mutant TP53. The median tumor-associated survival was 34.2 months for patients with normal TP53, compared with 8.9 months for those with mutant TP53. The latter had a 3-fold higher risk of dying (hazard ratio, 3.01; 95% confidence interval, 1.359-6.86). CONCLUSIONS: The biomarker TP53 divides esophageal cancer patients into 2 categories with markedly different outcomes: patients with a normal TP53 marker status may experience notable benefits from neoadjuvant chemotherapy with cisplatin/fluorouracil, whereas those with a mutant TP53 marker status appear to be at risk for lack of response. PMID- 25135240 TI - Historical perspectives of The American Association for Thoracic Surgery: David C. Sabiston, Jr (1924-2009). PMID- 25135239 TI - Reoperative "valve-in-valve" transapical transcatheter mitral valve replacement in a high-risk patient with a recent transapical transcatheter aortic valve replacement and a degenerated bioprosthetic mitral valve. PMID- 25135241 TI - Historical perspectives of The American Association for Thoracic Surgery: Keith Reemtsma (1925-2000). PMID- 25135243 TI - A novel methyltransferase from the intracellular pathogen Plasmodiophora brassicae methylates salicylic acid. AB - The obligate biotrophic pathogen Plasmodiophora brassicae causes clubroot disease in Arabidopsis thaliana, which is characterized by large root galls. Salicylic acid (SA) production is a defence response in plants, and its methyl ester is involved in systemic signalling. Plasmodiophora brassicae seems to suppress plant defence reactions, but information on how this is achieved is scarce. Here, we profile the changes in SA metabolism during Arabidopsis clubroot disease. The accumulation of SA and the emission of methylated SA (methyl salicylate, MeSA) were observed in P. brassicae-infected Arabidopsis 28 days after inoculation. There is evidence that MeSA is transported from infected roots to the upper plant. Analysis of the mutant Atbsmt1, deficient in the methylation of SA, indicated that the Arabidopsis SA methyltransferase was not responsible for alterations in clubroot symptoms. We found that P. brassicae possesses a methyltransferase (PbBSMT) with homology to plant methyltransferases. The PbBSMT gene is maximally transcribed when SA production is highest. By heterologous expression and enzymatic analyses, we showed that PbBSMT can methylate SA, benzoic and anthranilic acids. PMID- 25135242 TI - Prevalence, pattern and perceptions of cleft lip and cleft palate among children born in two hospitals in Kisoro District, Uganda. AB - BACKGROUND: Cleft lip with or without cleft palate is one of the most common congenital anomalies that affect the oro-facial region. The aim of the study was to determine the period prevalence, pattern and perceptions of cleft lip and cleft palate in children born between 2005 and 2010 in two hospitals in Kisoro District, Uganda. METHODS: The study involved a retrospective review of medical records of mothers who delivered live babies between January 2005 and December 2010 in Kisoro Hospital and St. Francis Hospital, Mutolere in Kisoro District. Key informant interviews of mothers (n = 20) of the children with cleft lip and/or clip palate and selected medical staff (n = 24) of the two hospitals were carried out. The data were analysed using descriptive statistics. RESULTS: Over the 6 year period, 25,985 mothers delivered live babies in Kisoro Hospital (n = 13,199) and St. Francis Hospital, Mutolere (n = 12,786) with 20 babies having oro facial clefts. The overall period prevalence of the clefts was 0.77/1,000 live births. Sixty percent (n = 12) of children had combined cleft lip and palate and the same proportion had clefts on the left side of the face. More boys were affected than girls: 13 versus 7. About 45% of mothers were hurt on realizing that they had delivered a child with an oro-facial cleft. Forty percent of mothers indicated that a child with oro-facial cleft was regarded as an outcast. About 91.7% (n = 22) of the medical staff reported that these children were not accepted in their communities. Surgical intervention and psychosocial support were the management modalities advocated for by most respondents. CONCLUSION/RECOMMENDATIONS: The period prevalence of combined cleft lip and palate in two hospitals in Kisoro District was comparable to some findings elsewhere. Cleft lip and cleft palate are a medical and psychosocial problem in Kisoro District that calls for sensitization and counseling of the families and communities of the affected children. The policy makers need to strategically plan for provision of rehabilitation with feeding obturators to facilitate easy feeding to gain weight before surgical intervention of the affected children. PMID- 25135244 TI - Intratympanic gentamicin treatment for Meniere's disease: a randomized, double blind, placebo-controlled trial on dose efficacy - results of a prematurely ended study. AB - BACKGROUND: Gentamicin is used as a therapeutic agent for Meniere's disease because of its vestibulotoxicity causing chemo-ablation of the vestibular sensory epithelia. Its use has increased in recent years. However, there is still no consensus about the dose regimen of gentamicin in the treatment of Meniere's disease. In this study two different dose regimen treatment protocols are compared in a placebo controlled study design. The primary objective is to quantify the treatment effect on dizziness, the secondary objective is hearing evaluation. METHODS: We performed a randomized, double-blind, placebo-controlled study in adults with unilateral Meniere's disease according to the AAO-HNS guidelines resistant to conservative medication. Three groups received four injections, administered weekly (four intratympanic injections with 40 mg/mL gentamicin solution, two injections gentamicin solution and two injections of placebo in random order, or four injections with placebo). Outcome measures were the score on the Dizziness Handicap Inventory and pure tone audiometry (PTA). Intended follow-up was 2 years. RESULTS: During follow-up one patient exceeded the accepted amount of hearing loss. Further, enrollment was very slow (until 12 months between two patients) and new insights showed an apparent benefit of intratympanic gentamicin treatment (ITG). Therefore we performed an unscheduled interim analysis which showed that PTA threshold shifts reached the stopping criteria in two more patients. Because of this, this study was ended. Of the three patients with the significant PTA threshold shift two were enrolled in the gentamicin group. CONCLUSION: No conclusions can be drawn concerning doses regimens. Now that new publications have shown that ITG treatment can be an effective and safe treatment, a placebo-controlled randomized controlled trial may not pass the ethical committee because of these recent reports in literature. Still, a dose regimen study (without placebo) on ITG treatment needs to be performed. TRIAL REGISTRATION: This trial was registered in The University Medical Center Utrecht/ Gelre hospital Apeldoorn. Protocol ID: 07/343, EudraCT number 2006-005913-37. PMID- 25135246 TI - Does aerobic exercise mitigate the effects of cigarette smoking on arterial stiffness? AB - The largest percentage of mortality from tobacco smoking is cardiovascular related. It is not known whether regular participation in exercise mitigates the adverse influence of smoking on vasculature. Accordingly, the authors determined whether regular aerobic exercise is associated with reduced arterial stiffness in men who smoke cigarettes. Using a cross-sectional study design, 78 young men were studied, including sedentary nonsmokers (n=20), sedentary smokers (n=12), physically active nonsmokers (n=21), and physically active smokers (n=25). Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). There were no group differences in height, body fat, and systolic and diastolic blood pressure. As expected, both physically active groups demonstrated greater maximal oxygen consumption and lower heart rate at rest than their sedentary peers. The sedentary smokers demonstrated greater baPWV than the sedentary nonsmokers (11.8+/-1 m/s vs 10.6+/-1 m/s, P=.036). baPWV values were not different between the physically active nonsmokers and the physically active smokers (10.8+/-1 m/s vs 10.7+/-1 m/s). Chronic smoking is associated with arterial stiffening in sedentary men but a significant smoking-induced increase in arterial stiffness was not observed in physically active adults. These results are consistent with the idea that regular participation in physical activity may mitigate the adverse effects of smoking on the vasculature. PMID- 25135245 TI - Open-source electronic data capture system offered increased accuracy and cost effectiveness compared with paper methods in Africa. AB - OBJECTIVES: Existing electronic data capture options are often financially unfeasible in resource-poor settings or difficult to support technically in the field. To help facilitate large-scale multicenter studies in sub-Saharan Africa, the African Partnership for Chronic Disease Research (APCDR) has developed an open-source electronic questionnaire (EQ). STUDY DESIGN AND SETTING: To assess its relative validity, we compared the EQ against traditional pen-and-paper methods using 200 randomized interviews conducted in an ongoing type 2 diabetes case-control study in South Africa. RESULTS: During its 3-month validation, the EQ had a lower frequency of errors (EQ, 0.17 errors per 100 questions; paper, 0.73 errors per 100 questions; P-value <=0.001), and a lower monetary cost per correctly entered question, compared with the pen-and-paper method. We found no marked difference in the average duration of the interview between methods (EQ, 5.4 minutes; paper, 5.6 minutes). CONCLUSION: This validation study suggests that the EQ may offer increased accuracy, similar interview duration, and increased cost-effectiveness compared with paper-based data collection methods. The APCDR EQ software is freely available (https://github.com/apcdr/questionnaire). PMID- 25135247 TI - Mallet fracture. PMID- 25135248 TI - The effects of ulnar styloid fractures on patients sustaining distal radius fractures. AB - PURPOSE: To determine if ulnar styloid fractures (USF) affect clinical outcome following distal radius fracture (DRF) in adults under 65 years of age. METHODS: This study involved 312 patients (aged 18-64) with surgically and nonsurgically treated DRFs. Patients were followed prospectively at baseline and 3, 6, and 12 months. The primary outcome was the Patient-Rated Wrist Evaluation (PRWE), and secondary outcomes were range of motion and grip strength. The USFs were classified by location (tip, middle, and base) and union status. RESULTS: There were 170 patients with isolated DRFs and 142 with associated USF (64 tip, 32 middle, and 46 base fractures). The mean age of the entire cohort was 48 years with 218 (70%) women. All USFs were treated nonoperatively. There was a trend of higher PRWE scores in DRFs associated with USFs compared to isolated DRFs throughout the study. Associated ulnar styloid base fractures had higher but clinically insignificant PRWE scores than isolated DRFs at 6 and 12 months. Patients with an associated USF had a slower recovery of wrist flexion and grip strength compared to isolated DRF, but values were comparable at 12 months. United USFs and nonunited USFs had similar PRWE scores at all time points. CONCLUSIONS: Adults under 65 years old with DRFs and associated USFs initially have greater pain and disability than those with isolated DRFs; however, this difference dissipated over time and was not significant at one year. No long-term differences in measured impairments were observed, but the presence of an associated USF resulted in a slower recovery of grip strength and wrist flexion. Presence of a USF nonunion did not significantly affect outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II. PMID- 25135249 TI - Evaluation of the PROMIS physical function computer adaptive test in the upper extremity. AB - PURPOSE: To compare psychometric and responder burden characteristics between the Patient-Reported Outcomes Measurement Information System Physical Function Computer Adaptive Test (PF CAT) and the Disabilities of Arm, Shoulder, and Hand (DASH) instruments in a tertiary hand and upper extremity practice. METHODS: Adult patients who presented to the clinic of 2 hand and upper extremity surgeons in a university-based tertiary care center were enrolled in this study. Participants received the DASH and PF CAT administered via tablet computer. Time to completion was recorded for both the DASH and PF CAT. We conducted statistical analyses to calculate Pearson correlation coefficients between the 2 instruments and performed a Rasch item response theory analysis to determine dimensionality, reliability, ceiling and floor effects, and item bias for each instrument. RESULTS: A total of 134 patients were included. Time to completion for the DASH was 262 seconds, and for the PF CAT 57 seconds. The instruments had strong correlation (r = 0.726). The item and Pearson reliability were 0.97 and 0.94, respectively, for the DASH and 0.99 and 0.96 for the PF CAT. The DASH and PF CAT had 5% and 5% of unexplained variance, respectively. The DASH exhibited 5% of ceiling effect and 1% floor effect whereas the PF CAT had no ceiling or floor effects. CONCLUSIONS: The psychometric characteristics of the Patient-Reported Outcomes Measurement Information System PF CAT instrument compared favorably with the DASH in a tertiary upper extremity practice. Patient time burden was significantly reduced with the PF CAT compared with the DASH. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III. PMID- 25135251 TI - Pediatric supracondylar humerus fractures. PMID- 25135250 TI - Selection of tendon grafts for distal radioulnar ligament reconstruction and report of a modified technique. AB - PURPOSE: To investigate the graft length necessary to complete a distal radioulnar ligament reconstruction and assess the suitability of several tendon graft sources. METHODS: We measured the graft length needed to complete the distal radioulnar ligament reconstruction in 7 fresh-frozen cadaver specimens. The pure tendon lengths of 7 tendon graft sources were measured: palmaris longus, extensor indicis proprius, slips of extensor digiti minimi and abductor pollicis longus, and portions of flexor carpi ulnaris, flexor carpi radialis, and extensor carpi ulnaris. A modified technique that allows for a shorter length of graft is also described, and the suitability of each graft source for this technique was assessed. RESULTS: The mean graft lengths needed to complete the original and modified reconstructions were 138 mm and 89 mm, respectively. The average length of the tendon graft when measured as pure tendon was: palmaris longus (127 mm), slip of extensor digiti minimi (112 mm), extensor indicis proprius (100 mm), partial flexor carpi radialis (87 mm), slip of abductor pollicis longus (69 mm), partial flexor carpi ulnaris (67 mm), and partial extensor carpi ulnaris (67 mm). The palmaris longus was too short for the original technique in the majority of specimens but was sufficient to complete the modified technique in every specimen that had a palmaris longus. Six specimens also had an extensor indicis proprius of suitable length for the modified technique. CONCLUSIONS: The length of donor graft required for the modified reconstruction was significantly less than that needed for the original reconstruction. Three specimens had no donor tendons sufficiently long to complete the original technique if a pure tendon graft were used, whereas the modified technique could be completed in all specimens. CLINICAL RELEVANCE: Many tendon graft sources in the upper extremity are of insufficient length to complete the distal radioulnar ligament reconstruction as described. A modified technique using suture anchors may be a useful alternative in such cases. PMID- 25135252 TI - Disease-modifying effects of TD-198946 on progressed osteoarthritis in a mouse model. PMID- 25135255 TI - Faculty development for clinical teachers in dental education. AB - Dental education has been reviewed, and suggestions for further enhancement include the implementation of faculty development activities to enhance teaching and learning environments. PURPOSE: The aim of this study was to gain insight into the participants' perceptions of outcomes of faculty development for clinical teachers and clinical learning environments as well as into the sustainability of such outcomes. METHODS: The program was organized in the form of (i) a 2-day seminar; (ii) collegial supervision and development projects; and (iii) a 1-day follow-up seminar. The participants' perceptions from the five first programs were studied. A Web-based questionnaire was sent to all participants, that is 3-27 months after completion of the program (follow-up survey). RESULTS: The outcomes of the program (response rate 70%) indicate a strong impact of the program on the clinical teachers' competence and on the clinical learning environments. The teachers report that they think more about what their students really learn, have become more conscious about how they supervise and have been stimulated to become better teachers. The learning environment as well as collaboration, and calibration between teachers have improved. The novice teachers report greater benefits than do the experienced teachers. The participants initiated a variety of development projects during the program. The majority of the participants continued the development activities. CONCLUSIONS: The faculty development program presented confirms that faculty development activities for clinical teachers based on theories of learning and experiences documented in the literature can be implemented with positive outcomes for individual teachers and for the learning environments. PMID- 25135253 TI - A homeostatic function of CXCR2 signalling in articular cartilage. AB - OBJECTIVE: ELR+ CXC chemokines are heparin-binding cytokines signalling through the CXCR1 and CXCR2 receptors. ELR+ CXC chemokines have been associated with inflammatory arthritis due to their capacity to attract inflammatory cells. Here, we describe an unsuspected physiological function of these molecules in articular cartilage homeostasis. METHODS: Chemokine receptors and ligands were detected by immunohistochemistry, western blotting and RT-PCR. Osteoarthritis was induced in wild-type and CXCR2(-/-) mice by destabilisation of the medial meniscus (DMM). CXCR1/2 signalling was inhibited in vitro using blocking antibodies or siRNA. Chondrocyte phenotype was analysed using Alcian blue staining, RT-PCR and western blotting. AKT phosphorylation and SOX9 expression were upregulated using constitutively active AKT or SOX9 plasmids. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. RESULTS: CXCL6 was expressed in healthy cartilage and was retained through binding to heparan sulfate proteoglycans. CXCR2(-/-) mice developed more severe osteoarthritis than wild types following DMM, with increased chondrocyte apoptosis. Disruption of CXCR1/2 in human and CXCR2 signalling in mouse chondrocytes led to a decrease in extracellular matrix production, reduced expression of chondrocyte differentiation markers and increased chondrocyte apoptosis. CXCR2-dependent chondrocyte homeostasis was mediated by AKT signalling since forced expression of constitutively active AKT rescued the expression of phenotypic markers and the apoptosis induced by CXCR2 blockade. CONCLUSIONS: Our study demonstrates an important physiological role for CXCR1/2 signalling in maintaining cartilage homeostasis and suggests that the loss of ELR+ CXC chemokines during cartilage breakdown in osteoarthritis contributes to the characteristic loss of chondrocyte phenotypic stability. PMID- 25135254 TI - NLRP3 and ASC suppress lupus-like autoimmunity by driving the immunosuppressive effects of TGF-beta receptor signalling. AB - OBJECTIVES: The NLRP3/ASC inflammasome drives host defence and autoinflammatory disorders by activating caspase-1 to trigger the secretion of mature interleukin (IL)-1beta/IL-18, but its potential role in autoimmunity is speculative. METHODS: We generated and phenotyped Nlrp3-deficient, Asc-deficient, Il-1r-deficient and Il-18-deficient C57BL/6-lpr/lpr mice, the latter being a mild model of spontaneous lupus-like autoimmunity. RESULTS: While lack of IL-1R or IL-18 did not affect the C57BL/6-lpr/lpr phenotype, lack of NLRP3 or ASC triggered massive lymphoproliferation, lung T cell infiltrates and severe proliferative lupus nephritis within 6 months, which were all absent in age-matched C57BL/6-lpr/lpr controls. Lack of NLRP3 or ASC increased dendritic cell and macrophage activation, the expression of numerous proinflammatory mediators, lymphocyte necrosis and the expansion of most T cell and B cell subsets. In contrast, plasma cells and autoantibody production were hardly affected. This unexpected immunosuppressive effect of NLRP3 and ASC may relate to their known role in SMAD2/3 phosphorylation during tumour growth factor (TGF)-beta receptor signalling, for example, Nlrp3-deficiency and Asc-deficiency significantly suppressed the expression of numerous TGF-beta target genes in C57BL/6-lpr/lpr mice and partially recapitulated the known autoimmune phenotype of Tgf-beta1 deficient mice. CONCLUSIONS: These data identify a novel non-canonical immunoregulatory function of NLRP3 and ASC in autoimmunity. PMID- 25135256 TI - Implementation of clinical governance in hospitals: challenges and the keys for success. AB - There is a number of models and strategies for improving the quality of care such as total quality management, continuous quality improvement and clinical governance. The policy of clinical governance is part of the governments overall strategy for monitoring, assuring and improving in the national health services organization. Clinical governance has been introduced as a bridge between managerial and clinical approaches to quality. For successful implementing of clinical governance, it is necessary to pay attention to firm foundations of the structure, including equipment, staffing arrangement, supporting specialties, and staff training. Therefore, as clinical governance improves safety and quality in health care services, the current situation in hospitals should be evaluated before any intervention while barriers and blocks on structure and process should be determined to select a method for changing them. Considering these points could guarantee success in implementation of clinical governance; otherwise there would be a little chance to achieve the desired results despite consumption of plenty of time and huge paper works. PMID- 25135257 TI - Melatonin improve the sperm quality in forced swimming test induced oxidative stress in nandrolone treated Wistar rats. AB - This study investigates the effects of melatonin on the sperm quality and testis weight after the combination of swimming exercise and nandrolone decanoate (DECA). Two groups of male Wistar rats were treated for eight weeks as follows; group A consist of CO (control), Sham, N (DECA), S (swimming) and NS (DECA plus swimming); and group B: Sham M (sham melatonin), M (melatonin), MN (melatonin plus DECA), MS (melatonin plus swimming), MNS (melatonin, DECA plus swimming). The motility of sperm was significantly improved in melatonin groups in comparison to N, S and NS groups (P<=0.05). The left testes weight was decreased in N, NS and MNS groups, and the right testes weight was decreased in N,S,NS, MS and MNS groups in compare with the control group. This study concluded that melatonin probably could improve the sperm motility and sex organs weight after the combination of DECA and exercise. PMID- 25135259 TI - Prevalence and severity of obsessive-compulsive disorder and their relationships with dermatological diseases. AB - Most obsessive-compulsive disorder (OCD) patients meet psychiatrists 5 to 10 years after onset of OCD .Its relatively high prevalence ratio and the delay in seeking help suggest that patients with OCD may seek help at non-psychiatric clinics. The present study was undertaken to provide some epidemiological data on the prevalence and severity of OCD in dermatological patients. The participants included 265 consecutive patients with primary dermatologic chief complaint. They were visited by a dermatologist and diagnosis of dermatological lesion was done according to ICD-10. All patients were visited by a psychiatry resident and were screened for OCD using the structured clinical interview for DSM-IV-TR (SCID-I). If the diagnosis of OCD has been made, the Yale-Brown obsessive compulsive scale(Y-BOCS) was used to evaluate the severity of OCD. To analyze the data student t-test for quantitative variables and X2 tests for categorical variables. From the total of 265 patients, 24 (9.1%) met the DSM-IV-TR criteria for OCD and 9 (37.5%) with OCD had previously been diagnosed with OCD, however, only three were treated pharmacologically. The most symptoms were pathological doubt (29.1%), fear of contamination (29.1%) and washing (54.16%). Severity of OCD according to Y-BOCS was evaluated among patients with OCD. Six (25%) were found with subclinical OCD, 11(45.8%) had mild OCD, six (25%) had moderate OCD, and one (4.2%) was detected with severe OCD. prevalence of OCD in dermatology clinic was higher compared with general population. PMID- 25135258 TI - The relationship between anthropometric parameters and bone mineral density in an Iranian referral population. AB - Osteoporosis is a common health concern in both developed and developing countries. In this study the association between anthropometric measures and osteoporosis was investigated in 3630 males and females visiting BMD clinic of Shariati Hospital, Tehran, Iran, a teaching hospital and referral center for osteoporosis affiliated to the Tehran University of Medical Sciences. Anthropometric measurements obtained and also Bone Mineral Density (BMD) measurement was done using a Lunar DPXMD densitometer. Data were analyzed using SPSS with Chi-square and ANOVA with post-hoc tests. Results showed that the weight, BMI and age had the strongest correlation with the BMD values in the studied people. While age is negatively correlated with BMD in all the studied people, a positive association was noted between weight, height and BMI and BMD parameters (P<0.01). It was concluded that certain anthropometric parameters (BMI and weight) can considerably affect one's risk of developing osteoporosis. Further research on the effect of these variables on the association of weight and BMD is needed. PMID- 25135260 TI - Total serum IgE concentration in patients with psoriasis: a case-control study. AB - Psoriasis is a chronic relapsing disorder that involves the skin, nails and joints. With regard to the role of the immune system in psoriasis, the current study compared serum IgE concentration in patients with psoriasis with control group. Current case-control study was conducted in Dermatology clinic of Razi hospital, Tehran University of medical sciences, Tehran, Iran in 2012. Fifty eight patients with psoriasis e referred to the clinic were assigned as patient group and 58 healthy subjects with matched age and sex as a control group. Patient's history, family history and demographic characteristics such as age and sex, duration and severity of disease using PASI, were collected and entered into a form. Consent form was obtained from participants. Serum IgE concentrations of both study groups were measured by electrochemiluminescence assay in the laboratory A total number of 58 patients with psoriasis, mean age of 44.15 (19-76 years) and 58 controls with matched age and sex were studied. Mean average of serum IgE concentration in the control group was 115.13 versus 200/06 concentration in patients group (P=0.16). Serum IgE concentration in 22.4% of patients versus 17.2% in controls was greater than normal concentration (P=0.48). No significant correlation was between serum IgE concentration and disease severity using PASI (P=0.11, r=0.21), neither a significant correlation with disease duration, age and gender. According to the present study, serum IgE concentrations are not greater in patients with psoriasis. IgE concentration is also not associated with the severity of psoriasis based on the PASI score, therefore, the role of IgE in psoriasis can be considered insignificant as some previous studies indicate. PMID- 25135261 TI - Rapid screening of diabetic polyneuropathy: selection of accurate symptoms and signs in an outpatient clinical setting. AB - Clinical assessment of distal symmetric polyneuropathy (DPN) involves the evaluation of symptoms and signs. Although there are numerous tools to evaluate DPN, there is still a need to determine the most sensitive, specific, and accurate tests to detect DPN in a busy outpatient clinical setting. A total of 107 patients with type 2 diabetes were examined using Michigan Neuropathy Screening Instrument (MNSI). Total score of the instrument was used as a standard to calculate sensitivity, specificity and diagnostic accuracy of every single item of MNSI to find the most accurate and applicable test for evaluation of DPN. In patients' history, the most sensitive (99.4%) and accurate (78%) symptoms were muscle cramp and weakness. Numbness and prickling had lower sensitivity (72.6% and 67.9%, respectively) but greater specificity (65.2% and 47.8%). In physical assessment, the most accurate signs were appearance of feet (81.3%), ankle reflexes (67.2%), and vibration perception (63.5%). Monofilament test had a sensitivity of 16.7%, accuracy of 31.7% with specificity of 87%. Findings show that symptoms such as a muscle cramp, weakness, numbness, and prickling, as well as signs such as ankle reflexes, appearance of feet, and vibration could be used as the most accurate tests for rapid diagnosis of DPN. In addition, the results suggest that monofilament examination may not be the optimum test to detect high risk patients. PMID- 25135262 TI - Comparison of fumaric acid 5% cream versus triamcinolone 0.1% cream in the treatment of hand eczema. AB - Hand eczema is a common distressing skin problem. It is an immune reaction to haptens. Thus, substances that inhibit Immune system can be effective in the treatment of hand eczema. In this study, topical fumaric acid 5% cream is compared with topical steroid in the treatment of hand eczema. Patients with hand eczema were randomly divided into two groups. One group received fumaric acid 5% in a cream base, and the other received triamcinolone 0.1% in the same cream base. Both groups used creams twice daily for one month. Patients were checked for erythema, excoriation, population and lichenification, EASI score, and pruritus before and after treatment. In both groups, the mean of all signs of the disease and EASI score decreased after one month of treatment. There was no significant difference between the two treatments in decreasing erythema, but excoriation, population, lichenification, EASI score and itching were all decreased more in triamcinolone 0.1 % group. Although fumaric acid can inhibit the immune system; it was less effective for the treatment of all signs of hand eczema except erythema in comparison to triamcinolone. These results may be justified for two reasons: low penetration of topical fumaric acid through the skin or a low concentration used in this study. PMID- 25135263 TI - An assessment of readiness for pre-implementation of electronic health record in Iran: a practical approach to implementation in general and teaching hospitals. AB - Readiness assessment provides a proper image of the existing conditions and an explanation of facilitated operational plans and functional approaches to successful implementation of electronic health record. Readiness assessment requires indices adjusted to particular conditions in each country. Therefore, the present study attempts to provide an acceptable model in Iran and to provide an assessment of public and teaching hospitals in medical education university. After reviewing related papers and descriptive study of five selected countries, the initial model was designed in the form of a questionnaire for analysis through Delphi and distributed among 30 experts nationwide. Along identification of components in the proposed method, a 7-point Likert scale was used to determine priority of each component. Then, all general -education hospitals at Tehran University of Medical Education were examined based on this model in terms of total, relative, or no readiness. The final model was designed in five dimensions: cultural, leadership and management, technical infrastructure, governance and operational dimensions; Educational Hospitals were evaluated in this dimension. 28.6 % of general--teaching hospitals are ready for pre implementation. It seems to establish uniform strategic and executive team in Health center is essential for the preparation them in abovementioned area in the least possible time. PMID- 25135264 TI - Results of nasolacrimal duct probing in children between 9-48 months. AB - Congenital nasolacrimal duct obstruction (CNLDO) is a common disease in children. The classic treatment of CNLDO is probing that was done around one year old. However, controversy exists regarding the outcome of probing in children older than one year. This study aimed to find the cure rate of initial probing for CNLDO and identify factors producing the failure rate in old age. In this retrospective interventional case series study, 100 eyes of 92 patients aged 9-48 months with CNLDO underwent probing with general anesthesia. According to the intraoperative results of probing, CNLDO were categorized in two groups of membranous obstruction at the end of nasolacrimal duct obstruction (NLD) and complex obstruction at canaliculus, lacrimal sac and N LD. Patients were categorized in three groups according to the age of probing into under 12, 12 to 24 and over 24 months. Success rate was defined as successful irrigation of NLD intraoperatively and absence of lacrimation and discharge at 1 week, one, three and six months postoperatively. The average age of patients and probing were 47.35+/-25.59 and 17.32+/-7.85 months respectively. Membranous obstruction accounted for 72% of patients and remainder had complex type. An overall cure rate of 91%, 89% and 60% was found in patients aged 9-12, 12-24 and 24-48 months respectively. Surgery success rate after six months was 91% in membranous group and 52% in complex group. There was a significant relation between the type of obstruction and opening of NLD (p<0.O01). This study showed that the probing failure of probing after one year was related to the complexity of obstruction rather than the age of the patient. It is recommended that probing could safely be done in under 4 years old. PMID- 25135265 TI - Frequency of exclusive breastfeeding and its affecting factors in Tehran, 2011. AB - This study was designed to assess the frequency of exclusive breastfeeding in two health centers of Shahid Beheshti University of Medical sciences in Khak Sefid, Tehran, Iran. A total of 175 mothers, referred for the third dose of their infants' DPT vaccination program participated in the study by completing a questionnaire regarding characteristics of their pregnancy, delivery and exclusive breastfeeding within the first six months of birth. Two-variable analysis and logistic regression test were applied to evaluate factors influencing exclusive breastfeeding. Results indicated that the frequency of exclusive breastfeeding, i.e., breastfeeding within the first six months of birth without the use of any other food with or without vitamin supplementation, was 31.17% (95% CI=23.77%-38.57%), which means 48 infants of 154<179 days old Among 154 infants (<179 days old) 48 did not have a history of being separated from their mothers. In logistic regression analysis, the variables which were directly associated with exclusive breastfeeding, with 0.05 significance level of alpha, included breastfeeding within the first hour of birth, eight times or more breastfeeding per day and receiving breastfeeding education during pregnancy. Variables with a negative association with breastfeeding included lack of breast milk, presence of a breast problem that could hinder breastfeeding, bottle feeding, physician or family's advice not to breastfeed and infant's refusal to breastfeed. Frequency of breastfeeding within the six months of birth is less than similar frequencies which are obtained by asking about breastfeeding on the day of the interview. It is recommended to apply real frequency for assessment, evaluation and programming of exclusive breastfeeding during the first six months of birth. PMID- 25135267 TI - Guyon's tunnel syndrome during pregnancy with concomitant anomalous arch of the ulnar nerve: a case report. AB - Numerous causes are reported for ulnar nerve compression at the wrist, known as Guyon's tunnel syndrome. In the present article, a patient with Guyon's tunnel syndrome during pregnancy concomitant with an anomaly of ulnar nerve is described. A 29-year-old Iranian woman presented with clinical features of Guyon's tunnel syndrome (pain and paresthesia in the fifth finger of the left hand and atrophy of the first dorsal interosseus muscle). Symptoms of the patient appeared during the third trimester of pregnancy. Electro diagnostic studies confirmed Guyon's tunnel syndrome. Surgical exploration revealed an anomalous arch of the ulnar nerve passing through the flexor carpi ulnaris (FCU) tendon. The anomalous arch of the ulnar nerve was released by resection of the segment of FCU tendon passing through the ulnar nerve arch. Therefore, in patients with Guyon's tunnel syndrome, the ulnar nerve anomaly should be kept in mind as a cause. Moreover, pregnancy may have a provocative effect on Guyon's tunnel syndrome similar to carpal tunnel syndrome (CTS). PMID- 25135266 TI - Effect of repetitive feedback on residents' communication skills improvement. AB - To evaluate the effect of frequent feedback on residents' communication skills as measured by a standardized checklist. Five medical students were recruited in order to assess twelve emergency medicine residents' communication skills during a one-year period. Students employed a modified checklist based on Calgary Cambridge observation guide. The checklist was designed by faculty members of Tehran University of Medical Science, used for assessment of students' communication skills. 24 items from 71 items of observational guide were selected, considering study setting and objects. Every two months an expert faculty, based on descriptive results of observation, gave structured feedback to each resident during a 15-minute private session. Total mean score for baseline observation standing at 20.58 was increased significantly to 28.75 after feedbacks. Results markedly improved on "gathering information" (T1=5.5, T6=8.33, P=0.001), "building relationship" (T1=1.5, T6=4.25, P<0.001) and "closing the session" (T1=0.75, T6=2.5, P=0.001) and it mildly dropped on "understanding patients view" (T1=3, T6=2.33, P=0.007) and "providing structure" (T1=4.17, T6=4.00, P=0.034). Changes in result of "initiating the session" and "explanation and planning" dimensions are not statically significant (P=0.159, P=0.415 respectively). Frequent feedback provided by faculty member can improve residents' communication skills. Feedback can affect communication skills educational programs, and it can be more effective if it is combined with other educational methods. PMID- 25135268 TI - Successful airway management in a patient with tracheal stenosis and tracheoesophageal fistula: a case report. AB - A twenty-year-old girl was referred with tracheal stenosis (TS) which was a consequence of prolonged intubation after head injury because of previous car accident. The patient was aphasic and had normal respiration. Fiberoptic bronchoscopy showed complete tracheal obstruction at second tracheal ring level. Distal trachea was normal through tracheostomy tube. Removal of the tracheostomy tube and blind reinsertion with a new one was complicated with hypoxia and respiratory distress. Fibrotic bronchoscopy revealed large tracheoesophageal fistula (TEF) below tracheal obstruction. Reinsertion of the tracheostomy tube by fiber optic bronchoscope was successful. Multidetector CT scan was performed on the same day with confirmation of TS combined with TEF. Surgery was performed on the next day. No clinical evidence of TEF was found in back history. Inadequate evaluation of the whole length of the trachea during the first bronchoscopy was the reasons for missing TEF. TEF should be considered in patients with TS in spite of no typical symptom such as food aspiration or pulmonary infections. PMID- 25135269 TI - Cervical sympathetic schwannoma: report of two cases and review of the literature. AB - This study describes two cases of cervical sympathetic schwannoma operated at department of vascular surgery and review the literature to clarify the demographic, diagnostic, and therapeutic features of these rare lesions for the first time. Two 32- and 59-year-old ladies both presenting with a painless cervical mass were referred to our service with the initial diagnosis of carotid body tumor. At the operation, mobile masses which could be easily dissected from the surrounding arteries and veins, except for the cervical sympathetic trunk were observed. Micro-surgical techniques helped us with removing the lesions with saving the sympathetic trunk in both cases. No permanent deficits were observed post-operatively in patients. Angiographic studies can provide the only pre operative clues to diagnose a sympathetic schwannoma. Total removal of the lesion at the expense of sacrificing the sympathetic nerve is associated with minimal neurologic deficits which are well tolerated by the patient. PMID- 25135270 TI - Atypical respiratory distress in a newborn: a diagnostic dilemma. AB - Neonatal respiratory distress is a very common problem in our practice. The causes may be respiratory, cardiovascular, central, metabolic, haematological and surgical. The cause of distress due to transient myocardial depression is not very common in mild asphyxia. We present a case having transient myocardial depression with severe respiratory distress and features of shock in a mild asphyxiated baby. PMID- 25135271 TI - A case with pachyonychia congenita and B-cell lymphoma. AB - Pachyonychia congenital (PC) is a rare autosomal dominant genodermatosis characterized hyperkeratosis affecting the nails and palmoplantar areas, oral leukokeratosis, and cystic lesions. A 39-year-old woman with PC type 1 (Jadassohn Lewandowsky syndrome) and B-cell lymphoma is described. No similar disorders or parental consanguinity were found in her family. Typical features of PC developed since her early childhood and the diagnosis of B-cell lymphoma was established seven years ago, without a clear causal relation between these entities. Despite inherent limitations of a single case, this report may contribute to PC understanding. PMID- 25135275 TI - [General anesthesia for ambulatory surgery : Clinical pharmacological considerations on the practical approach]. AB - Due to modern surgical and anesthesia techniques, many patients undergoing small or even medium surgical procedures will recover within minutes and can then be discharged after a few hours of monitoring. Aside from an optimized surgical technique, a precise and differentiated anesthesia concept is needed to guarantee rapid recovery and home readiness. Nowadays, remifentanil-propofol represents the standard regime in ambulatory anesthesia. The use of alfentanil, desfluran or sevofluran is also possible whereas other intravenous or inhaled anesthetics or other opioids are rarely used. If endotracheal intubation is necessary, a reduced intubating dose of neuromuscular blockers (NMB), such as mivacurium, atracurium and rocuronium, i.e. 1-1.5-times the 95 % effective dose (ED95) is a good possibility to accelerate neuromuscular recovery while still having acceptable intubation conditions. Due to its limitations and contraindications, succinylcholine is not the first choice but may be used in non-fasting patients in need of urgent (ambulatory) surgery, e.g. in bleeding women undergoing dilation and curettage. Even with these reduced dosages monitoring of neuromuscular recovery is crucial and should be applied to all patients when NMBs are used. Furthermore, patients should receive a risk-adapted postoperative nausea and vomiting (PONV) prophylaxis, e.g. with 4 mg dexamethasone and 4 mg ondansetron. Postdischarge nausea and vomiting (PDNV) should be anticipated by a new risk score and prophylaxis or treatment should be initiated. For postoperative pain relief, local or regional anesthesia techniques, such as infiltration, field or nerve blocks should be applied where possible. In addition, non-opioid analgesics are the basic treatment while longer-lasting opioids are only necessary for some patients. PMID- 25135276 TI - Trends in hospitalizations and outcomes for acute cardiovascular disease and stroke, 1999-2011. AB - BACKGROUND: During the past decade, efforts focused intensely on improving the quality of care for people with, or at risk for, cardiovascular disease and stroke. We sought to quantify the changes in hospitalization rates and outcomes during this period. METHODS AND RESULTS: We used national Medicare data to identify all Fee-for-Service patients >=65 years of age who were hospitalized with unstable angina, myocardial infarction, heart failure, ischemic stroke, and all other conditions from 1999 through 2011 (2010 for 1-year mortality). For each condition, we examined trends in adjusted rates of hospitalization per patient year and, for each hospitalization, rates of 30-day mortality, 30-day readmission, and 1-year mortality overall and by demographic subgroups and regions. Rates of adjusted hospitalization declined for cardiovascular conditions (38.0% for 2011 compared with 1999 [95% confidence interval (CI), 37.2-38.8] for myocardial infarction, 83.8% [95% CI, 83.3-84.4] for unstable angina, 30.5% [95% CI, 29.3-31.6] for heart failure, and 33.6% [95% CI, 32.9-34.4] for ischemic stroke compared with 10.2% [95% CI, 10.1-10.2] for all other conditions). Adjusted 30-day mortality rates declined 29.4% (95% CI, 28.1-30.6) for myocardial infarction, 13.1% (95% CI, 1.1-23.7) for unstable angina, 16.4% (95% CI, 15.1 17.7) for heart failure, and 4.7% (95% CI, 3.0-6.4) for ischemic stroke. There were also reductions in rates of 1-year mortality and 30-day readmission and consistency in declines among the demographic subgroups. CONCLUSIONS: Hospitalizations for acute cardiovascular disease and stroke from 1999 through 2011 declined more rapidly than for other conditions. For these conditions, mortality and readmission outcomes improved. PMID- 25135277 TI - The post-translational modification of the Clostridium difficile flagellin affects motility, cell surface properties and virulence. AB - Clostridium difficile is a prominent nosocomial pathogen, proliferating and causing enteric disease in individuals with a compromised gut microflora. We characterized the post-translational modification of flagellin in C. difficile 630. The structure of the modification was solved by nuclear magnetic resonance and shown to contain an N-acetylglucosamine substituted with a phosphorylated N methyl-l-threonine. A reverse genetics approach investigated the function of the putative four-gene modification locus. All mutants were found to have truncated glycan structures by LC-MS/MS, taking into account bioinformatic analysis, we propose that the open reading frame CD0241 encodes a kinase involved in the transfer of the phosphate to the threonine, the CD0242 protein catalyses the addition of the phosphothreonine to the N-acetylglucosamine moiety and CD0243 transfers the methyl group to the threonine. Some mutations affected motility and caused cells to aggregate to each other and abiotic surfaces. Altering the structure of the flagellin modification impacted on colonization and disease recurrence in a murine model of infection, showing that alterations in the surface architecture of C. difficile vegetative cells can play a significant role in disease. We show that motility is not a requirement for colonization, but that colonization was compromised when the glycan structure was incomplete. PMID- 25135279 TI - The adductor ratio: a new tool for joint line reconstruction in revision TKA. AB - PURPOSE: In this study, the value of the adductor tubercle as landmark for joint line reconstruction in revision total knee arthroplasty (TKA) was investigated. METHODS: On 100 calibrated full-leg standing radiographs obtained from healthy volunteers, distances from the medial epicondyle, the lateral epicondyle, the adductor tubercle, the fibular head and the centre of the knee to the joint line were determined. RESULTS: The average distance to the joint line from the medial epicondyle, the lateral epicondyle, the adductor tubercle and the fibular head was found to be 27.7 mm (SD 3.0), 27.1 mm (SD 2.7), 44.6 mm (SD 4.3) and 15.1 mm (SD 3.7), respectively. The distance from the adductor tubercle (R = 0.82) and the centre of the knee (R = 0.86) to the joint line showed a strong and linear correlation with the femoral width. The medial epicondyle, the lateral epicondyle and the fibular head showed less strong correlations. There was no significant correlation with the limb alignment. The adductor ratio was defined as the distance from adductor tubercle to the joint line divided by the femoral width and was found to be 0.52 (SD 0.027) with only small inter-individual variation. The adductor ratio was the most accurate ratio and reconstructed the joint line within 4 mm of its original level in 92% of the cases. CONCLUSION: The adductor ratio is a reliable and accurate tool for joint line reconstruction in revision TKA. It was found to be more accurate then the use of absolute distances and the epicondylar ratios. This study supports the use of the adductor tubercle for joint line reconstruction in revision TKA. LEVEL OF EVIDENCE: II. PMID- 25135280 TI - Early surrender to knee arthroplasty.... Not so fast.... Let the knee tissue preservation and function sustainability dialogue begin! PMID- 25135278 TI - Infiltrating T cells promote prostate cancer metastasis via modulation of FGF11 >miRNA-541->androgen receptor (AR)->MMP9 signaling. AB - Early clinical studies suggested infiltrating T cells might be associated with poor outcomes in prostate cancer (PCa) patients. The detailed mechanisms how T cells contribute to PCa progression, however, remained unclear. Here, we found PCa cells have a better capacity to recruit more CD4(+) T cells than the surrounding normal prostate cells via secreting more chemokines-CXCL9. The consequences of more recruited CD4(+) T cells to PCa might then lead to enhance PCa cell invasion. Mechanism dissection revealed that infiltrating CD4(+) T cells might function through the modulation of FGF11->miRNA-541 signals to suppress PCa androgen receptor (AR) signals. The suppressed AR signals might then alter the MMP9 signals to promote the PCa cell invasion. Importantly, suppressed AR signals via AR-siRNA or anti-androgen Enzalutamide in PCa cells also enhanced the recruitment of T cells and the consequences of this positive feed back regulation could then enhance the PCa cell invasion. Targeting these newly identified signals via FGF11-siRNA, miRNA-541 inhibitor or MMP9 inhibitor all led to partially reverse the enhanced PCa cell invasion. Results from in vivo mouse models also confirmed the in vitro cell lines in co-culture studies. Together, these results concluded that infiltrating CD4(+) T cells could promote PCa metastasis via modulation of FGF11->miRNA-541->AR->MMP9 signaling. Targeting these newly identified signals may provide us a new potential therapeutic approach to better battle PCa metastasis. PMID- 25135282 TI - Upper-extremity spinal reflex inhibition is reproducible and strongly related to grip force poststroke. AB - PURPOSE: Impaired reflex regulation is assumed to contribute to upper-extremity motor impairment poststroke; however, the relationship between reflex inhibition and motor function remains unclear. To address this question, it is first necessary to determine the reproducibility of reflex responses. The objective of this study was to establish the test-retest reliability of flexor carpi radialis H-reflex inhibition in healthy control and stroke participants and investigate the correlation between H-reflex inhibition and grip strength. MATERIALS AND METHODS: Eighteen persons poststroke (mean +/- SD: age 63 +/- 13 years; 6 +/- 5 years poststroke; 13 males) and 16 healthy controls (age: 62 +/- 12 years) participated. Reflex inhibition was tested on 2 separate days by conditioning the H-reflex with radial nerve stimulation at two different interstimulus intervals: 13 ms (presynaptic Ia inhibition-PSI) and 0 ms (disynaptic inhibition). Pearson's and intraclass correlation coefficients [two-way mixed model-ICC (1, 2)], and standard error of measurement (SEM) were calculated. RESULTS: Relative reliability (ICCs) ranged from good to excellent (0.61-0.78). SEM was low (range 10-19%, stroke; 15-20%, healthy controls). Paretic grip strength and paretic limb PSI revealed a positive correlation (r = 0.70; p < 0.0125). Disynaptic inhibition and paretic grip strength were not correlated. CONCLUSIONS: To our knowledge, this is the first study to demonstrate reproducibility of reflex inhibition in individuals poststroke. Furthermore, we quantify smallest real differences, which provide an estimate of the magnitude of effect required to determine a meaningful change, exceeding measurement error. The correlation between PSI and grip strength suggests the potential contribution of PSI to grip force production and upper-extremity motor function. PMID- 25135283 TI - A familial form of benign paroxysmal positional vertigo maps to chromosome 15. AB - AIM: Benign positional paroxysmal vertigo (BPPV) is characterized by short-lived episodes of vertigo in association with rapid changes in head position, most commonly extension and rotation of the neck while supine. It has been clinically observed that there is a subgroup of patients in whom the BPPV disease is inherited in an autosomal dominant fashion. However, little is known about the familial/genetic factors that may contribute to a predisposition to develop the disease. MATERIALS AND METHODS: We ascertained and performed a genome-wide scan on a three-generation family in which multiple family members developed BPPV. We performed whole genome mapping with 400 microsatellite repeat markers and analyzed this trait using both autosomal dominant and recessive models of inheritance. RESULTS: Two point linkage analysis showed LOD scores of one or greater than one on chromosomes 7, 15, 16 and 20. Independent of the model of inheritance, the highest two-point LOD scores localized to same marker on chromosome 15. Multipoint linkage analysis showed the highest LOD score of 2.84 to markers on chromosome 15 with the autosomal dominant model. Haplotype reconstruction indicates that the BPPV gene in this family maps to a critical chromosomal 15 interval between markers GATA151F03N and GATA85D02. CONCLUSIONS: Discovery of a BPPV gene (or genes) will facilitate a better understanding of not only BPPV, but also the vestibular system. In addition, with improved understanding of the pathophysiology the potential development of alternative therapies for BPPV may be possible. PMID- 25135281 TI - The tumor suppressor prostate apoptosis response-4 (Par-4) is regulated by mutant IDH1 and kills glioma stem cells. AB - Prostate apoptosis response-4 (Par-4) is an endogenous tumor suppressor that selectively induces apoptosis in a variety of cancers. Although it has been the subject of intensive research in other cancers, less is known about its significance in gliomas, including whether it is regulated by key driver mutations, has therapeutic potential against glioma stem cells (GSCs), and/or is a prognostic marker. We found that patient-derived gliomas with mutant isocitrate dehydrogenase 1 have markedly lower Par-4 expression (P < 0.0001), which was validated by The Cancer Genome Atlas dataset (P = 2.0 E-13). The metabolic product of mutant IDH1, D-2-hydroxyglutarate (2-HG), can suppress Par-4 transcription in vitro via inhibition of promoter activity as well as enhanced mRNA degradation, but interestingly not by direct DNA promoter hypermethylation. The Selective for Apoptosis induction in Cancer cells (SAC) domain within Par-4 is highly active against glioma cells, including orthotopic xenografts of patient derived primary GSCs (P < 0.0001). Among high-grade gliomas that are IDH1 wild type, those that express more Par-4 have significantly longer median survival (18.4 vs. 8.0 months, P = 0.002), a finding confirmed in two external GBM cohorts. Together, these data suggest that Par-4 is a significant component of the mutant IDH1 phenotype, that the activity of 2-HG is complex and can extend beyond direct DNA hypermethylation, and that Par-4 is a promising therapeutic strategy against GSCs. Furthermore, not every effect of mutant IDH1 necessarily contributes to the overall favorable prognosis seen in such tumors; inhibition of Par-4 may be one such effect. PMID- 25135284 TI - Occurrence of Hashimoto's thyroiditis among the patients with Sydenham's chorea. AB - AIM: The purpose of this study was to examine the possible association of Hashimoto's thyroiditis (HT) with Sydenham's chorea (SC). MATERIALS AND METHODS: A total of 25 SC patients and 25 patients with the diagnosis of HT were included in the study. Neurological, cardiac, radiological abnormalities, clinical findings, and biochemical analysis were evaluated. RESULTS: Heart murmur as a result of mitral valve deformation was present in all SC group patients. No neurologic and cardiac abnormalities were noted in HT group. Serum thyroid stimulating hormone (TSH), anti-thyroid peroxidase, and anti-thyroglobulin levels were found to be high in 4 patients of the SC group and called as SC with HT group. Significant elevation of serum TSH levels in SC with HT group (31.75 +/- 3.71 MUU/ml) was observed when compared to HT group (12.60 +/- 4.24 MUU/ml, p < 0.05). CONCLUSION: These results showed that HT can be occurred among the patients with SC with cardiac involvement. PMID- 25135285 TI - Glycemic control: a combination of lifestyle management and the use of drugs. AB - Some 30% of contemporary cardiology patients have coexisting known diabetes, and another 40% have either undiagnosed diabetes or prediabetes. There is still no final conclusive evidence of cardiovascular benefit by good glycemic control in type 2 diabetes, although studies like the United Kingdom Prospective Diabetes Study (UKPDS) and the Prospective Pioglitazone Clinical Trial in Macrovascular Events, and meta-analyses based on these and other randomized controlled trials of blood glucose-lowering therapies have been encouraging. On the other hand, microvascular disease is clearly reduced by good glycemic control. Structured education has remained a mandatory prerequisite of any successful treatment. Not only is appropriate weight management by diet and exercise able to revert new onset diabetes to normal, but it is also the foundation of any successful pharmacotherapy of diabetes. Aiming at normal fasting plasma glucose concentrations of 5.3 mmol/L or 95 mg/dL appears to be safe since publication of the long-term outcome results of the Outcome Reduction with an Initial Glargine INtervention trial. Individualized target glycosylated hemoglobin levels as near to normal as safely possible (i.e., <7% and avoiding hypoglycaemia) are the goal for glycemic control. Hypoglycemia seems to emerge as a real concern in cardiology patients. Based on the findings of UKPDS, including the "legacy" study, metformin is the most widely recommended first-line drug therapy in type 2 diabetes, also in terms of preventing cardiovascular complications. An alternate first-line option in some parts of the world, especially Asian countries, is the class of alpha-glucosidase inhibitors. In most patients, combination therapies with two or three classes of drugs are warranted. Early combination are the golden strategy as type 2 diabetes is a multi-causal disease; the various classes of drugs have distinct and synergistic modes of action, and the blood glucose lowering efficacy of these drugs is more or less fully maintained in combination. The recent joint American Diabetes Association/European Association for the Study of Diabetes position statement mentions five options as step two of the treatment algorithm for combination with metformin: sulfonylureas, pioglitazone, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, and basal insulin. PMID- 25135286 TI - The resoluteTM integrity zotarolimus-eluting stent in coronary artery disease: a review. AB - The introduction of first-generation drug-eluting stents (DES) was a major advance in the percutaneous treatment of coronary artery disease, with DES significantly reducing the incidence of restenosis and major adverse coronary events compared with bare metal stents. Next-generation DES now utilizes lower profiles, thinner struts, and other technological advances to help extend their safety and efficacy. Importantly, studies of next-generation devices have now gone beyond controlled clinical trials with selected populations to registries and studies with all-comer populations, where more diverse and complex sets of patients and lesions have been managed. Thus, a large body of evidence and comparative data about the safety and efficacy of these devices has accumulated. The ResoluteTM zotarolimus-eluting stent (R-ZES; Medtronic Inc., Santa Rosa, CA, USA) is a next-generation DES that uses a novel biocompatible polymer on a cobalt alloy stent platform to extend the duration of drug elution and improve the stent's efficacy. The IntegrityTM platform (Medtronic, Inc., Santa Rosa, CA, USA) used in the most recent iteration of the R-ZES stent further enhances the flexibility and deliverability of the stent in complex lesions by incorporation of a continuous sinusoidal design. In the following review, the clinical data is critically examined for the R-ZES and discuss its performance using comparative data currently available for next-generation DES. It is concluded that R-ZES use in complex patients and lesions is associated with durable efficacy and safety and represents another generational improvement in DES technology, which undoubtedly will enhance patient outcomes postpercutaneous coronary interventional. PMID- 25135287 TI - Current and emerging antiarrhythmic drug therapy for ventricular tachycardia. AB - Ventricular arrhythmias, including ventricular fibrillation (VF) and sustained ventricular tachycardia (VT), are the principal causes of sudden cardiac death in patients with structural heart disease. While coronary artery disease is the predominant substrate associated with the development of VT, these arrhythmias are known to occur in a variety of disorders, including dilated cardiomyopathy, valvular and congenital heart disease, and cardiac ion channelopathies such as the long QT syndrome. In a minority of patients, VT occurs in the absence of structural heart disease. Despite the established mortality benefit of the implantable cardioverter defibrillator (ICD) in patients at risk of lethal arrhythmias, recurrent VT/VF events continue to be a source of morbidity and impaired quality of life in such patients. Antiarrhythmic therapy is indicated in select patients to treat symptomatic VT episodes, to reduce the incidence of ICD shocks, and potentially to improve quality of life and reduce hospitalizations related to cardiac arrhythmia. The primary adverse effects of antiarrhythmic medications are related to both cardiac and extracardiac toxicity, including the risk of proarrhythmia. Current drug therapy for ventricular arrhythmia has been limited by suboptimal efficacy in many patients, resulting in recurrent VT/VF events, and by drug toxicity or intolerance leading to discontinuation in a large percentage of patients. Amiodarone and sotalol are the principal agents used in the chronic treatment of VT. In addition, dronedarone and dofetilide, agents approved for the treatment of atrial fibrillation, and ranolazine, an antianginal agent, have been demonstrated to be protective against ventricular arrhythmia in small clinical studies. Finally, advances in basic electrophysiology have uncovered new molecular targets for the treatment of ventricular arrhythmia, and pharmacologic agents directed at these targets may emerge as promising VT treatments in the future. The roles of these current and emerging therapies for the treatment of VT in humans will be summarized in this review. PMID- 25135288 TI - Oral antiplatelet therapy in acute coronary syndromes: recent developments. AB - The purpose of this article is to summarize the current knowledge about treatment with oral platelet inhibitors in patients with acute coronary syndrome (ACS). Antiplatelet therapy has been shown to improve the prognosis of patients with ACS with ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation ACS (NSTE-ACS). Aspirin should be given with a loading dose of 250-500 mg, followed by 75-100 mg/day. Dual antiplatelet therapy is recommended for all patients with ACS for 12 months regardless of the initial revascularization strategy. Clopidogrel should be administered at first medical contact in STEMI with a loading dose of 600 mg. In patients with ACS and percutaneous coronary intervention (PCI) 2 * 75 mg clopidogrel should be given daily over 7 days, while in all other patients 75 mg per day appears to be sufficient. The two newer adenosine diphosphate-receptor antagonists prasugrel and ticagrelor lead to a more rapid and effective inhibition of platelet aggregation compared with clopidogrel, which was associated with an improved clinical outcome in two large randomized studies. Prasugrel is indicated in patients with ACS undergoing PCI and was most effective in diabetics and in patients with STEMI. In the recent TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes trial in medically treated patients with NSTE-ACS, prasugrel did not significantly reduce ischemic events compared with clopidogrel. Ticagrelor has been studied in the whole spectrum of ACS patients and reduced cardiovascular and total mortality in comparison with clopidogrel. The greatest benefit has been observed in patients with planned conservative treatment and in patients with impaired renal function. Expanding antiplatelet therapy from dual to triple therapy including a platelet thrombin receptor antagonist in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome trial was not associated with a significant reduction in the primary combined endpoint but an increase in bleeding complications. However, in the Thrombin Receptor Antagonist in Secondary Prevention of atherothrombotic ischemic events study in patients with prior myocardial infarction, vorapaxar on top of standard antiplatelet therapy was effective. PMID- 25135289 TI - Thrombin receptor antagonism in antiplatelet therapy. AB - Activated platelets play a crucial role in the pathogenesis of atherothrombotic disease and its complications. Even under treatment of antiplatelet drugs, such as acetylsalicylic acid and P2Y12 antagonists, morbidity and mortality rates of thromboembolic complications remain high. Hence, the therapeutic inhibition of protease-activated receptor (PAR)-1, which is activated by thrombin, is a novel promising approach in antiplatelet therapy. Recent data suggest that PAR-1 is mainly involved in pathological thrombus formation, but not in physiological hemostasis. Therefore, PAR-1 inhibition offers the possibility to reduce atherothrombotic events without increasing bleeding risk. So far, two emerging PAR-1 antagonists have been tested in clinical trials: vorapaxar (SCH530349; Merck & Co., Whitehouse Station, NJ, USA) and atopaxar (E5555; Eisai, Tokyo, Japan). Although in TRA-CER vorapaxar showed an unfavorable profile for patients with acute coronary syndrome in addition to standard therapy, it revealed promising results for patients with prior myocardial infarction in TRA 2P-TIMI50. Depending on the status of clinical approval, vorapaxar might be an option for patients with peripheral arterial disease to reduce limb ischemia. The second PAR I antagonist, atopaxar, tended towards reducing major cardiovascular adverse events in acute coronary syndrome patients in a phase II trial. However, although statistically not significant, bleeding events were numerically increased in atopaxar-treated patients compared with placebo. Furthermore, liver enzymes were elevated and the relative corrected QT interval was prolonged in atopaxar-treated patients. Currently, the development of atopaxar by Eisai is discontinued. The future of this novel class of antithrombotic drugs will depend on the identification of patient groups in which the risk-benefit ratio is favorable. PMID- 25135290 TI - Optimal choice of coronary revascularization and stent type in diabetic patients with coronary artery disease. AB - Patients with diabetes mellitus (DM) are prone to a diffuse and accelerated form of coronary artery disease (CAD), which in turn is a major cause of cardiac related morbidity and mortality. Compared with patients without diabetes, patients with diabetes undergoing coronary revascularization are at higher risk of procedural, short-, and long-term cardiovascular events and mortality. Although coronary artery bypass grafting (CABG) has been regarded as the primary revascularization strategy in diabetic patients with complex CAD, percutaneous coronary intervention (PCI) is an effective revascularization alternative, due to remarkable advances in stent devices and adjunctive drug therapies. Outcomes data, from subgroup analyses and small-sized clinical trials and large registries, have suggested that PCI with current stent technology showed comparable long-term risks of mortality and hard endpoints, but higher risk of repeat revascularization for the diabetic population compared to CABG. However, the recent landmark International Future REvascularization Evaluation in patients with diabetes mellitus: optimal management of Multivessel disease (FREEDOM) trial provides compelling evidence of the superiority of CABG over PCI in reducing the rates of death, myocardial infarction, at the expense of stroke, in patients with diabetes with advanced CAD. When opting for PCI in patients with diabetes, currently used drug-eluting stents (DES) are more efficient in reducing the risk of repeat revascularization without compromising safety outcomes, compared to bare-metal stents. The selection of a specific type of DES in patients with diabetes is controversial and therefore more data comparing second- and newer generation DES for patients with diabetes are currently needed. Also, efforts to make more advanced DES platforms suitable for patients with diabetes with complicated angiographic features are still ongoing. PMID- 25135291 TI - Balancing antiplatelet and anticoagulant therapies in patients with cardiovascular disease. AB - Anticoagulation is needed for stroke prevention in patients with atrial fibrillation. Antiplatelet therapy is essential for the prevention of stent thrombosis and the reduction of cardiovascular events in patients who undergo coronary stenting and suffer acute coronary syndromes. When these conditions overlap, the individual antithrombotic strategies are commonly combined, and the efficacy benefit of triple oral antithrombotic therapy is assumed to outweigh the bleeding risk based on the available data. Recent studies have investigated this topic further, including the first randomized controlled trial to address this issue. This new evidence challenges previous assumptions and may have implications for future practice and investigation. PMID- 25135292 TI - Fenestrated atrial septal defect percutaneously occluded by a single device: procedural and financial considerations. AB - A 45-year-old patient presented with a cerebrovascular attack and was subsequently found to have a multi-fenestrated atrial septal defect. Various therapeutic options for percutaneous transcatheter closure with their respective benefits and flaws are discussed, as well as procedural and financial considerations. The decision making process leading to a successful result using a single occlusive device is presented, alongside a review of the literature. PMID- 25135293 TI - An extremely rare combination: pneumopericardium, pneumoperitoneum, and subcutanous emphysema-a case report. AB - Pneumopericardium, an accumulation of air in the pericardial cavity, occurs very rarely as compared to pneumothorax and pneumomediastinum. Clinical presentation is variable, patients are frequently asymptomatic, and mild cases usually resolve spontaneously. However, it may lead to pericardial tamponade, which requires rapid diagnosis and treatment that can be lifesaving. The traditional diagnostic, simple method of diagnosis is via an upright chest X-ray. Typical findings can be detected and a differential diagnosis can be made between pneumomediastinum and pneumopericardium. Echocardiography and chest computed tomography scans can also support the diagnosis. Only one case of pneumopericardium after surgical pericardiotomy has been reported in the literature so far. In this case report, iatrogenic pneumopericardium, which resolved spontaneously after surgical pericardiotomy, was reported in a 19-year-old patient who had a rejected liver transplantation, and had liver and kidney failure with pericardial tamponade. In this case, pneumopericardium was accompanied by pneumoperitoneum and subcutaneous emphysema; an extremely rare combination. PMID- 25135295 TI - Anti-inflammatory effect of a novel food Cordyceps guangdongensis on experimental rats with chronic bronchitis induced by tobacco smoking. AB - Cordyceps guangdongensis T. H. Li, Q. Y. Lin & B. Song (Cordycipitaceae) is a novel food approved by the Ministry of Public Health of China in 2013. Preliminary studies revealed that this novel food has multiple pharmacological activities such as anti-fatigue effect, antioxidant ability, prolonging life, anti-avian influenza virus activity, and therapeutic effect on chronic renal failure. However, the anti-inflammatory effect on chronic bronchitis and the effective constituent are still unknown. The purpose of this study was to investigate both the anti-inflammatory effect of the edible fungus on experimental rats with chronic bronchitis induced by tobacco smoking, and the pilot effective constituent. Test rats were intragastrically administered with 3 doses of hot-water extract from C. guangdongensis (0.325, 0.65 and 1.30 g kg(-1) bw daily for low, middle and high dose, respectively) for 26 days. Biochemical indices and histological examinations in rats with chronic bronchitis induced by tobacco smoking were determined. The content and molecular weights of the polysaccharide from the hot-water extract were detected by the phenol-sulfuric acid method and gel permeation chromatography, respectively. Biochemical indices in the low, middle and high-dose groups with the hot-water extract of C. guangdongensis were only 53.4%, 46.0% and 40.4% of those in the model control group (total leukocytes), respectively; 70.7%, 60.3% and 58.1% (macrophages); 33.0%, 26.8% and 16.1% (neutrophils); and 22.2%, 23.5% and 13.6% (lymphocytes) of those in the model control group. The bronchial lesions and inflammatory cell infiltration were significantly alleviated in all groups with hot-water extract of C. guangdongensis. This study indicates that the hot-water extract from C. guangdongensis has a significant anti-inflammatory effect on chronic bronchitis. The content of the polysaccharide was 6.92%; the molecular weights of the 3 polysaccharide components were respectively 1.28 * 10(6), 2.36 * 10(4) and 5.21 * 10(3) Da. PMID- 25135294 TI - Dabigatran excess: case report and review of the literature. AB - INTRODUCTION: Novel oral anticoagulants are increasingly used for stroke prophylaxis in patients with non-valvular atrial fibrillation. While these agents offer a more predictable pharmacokinetic profile, the lack of readily available laboratory tests to monitor the level of anticoagulation and absence of an antidote or established therapies to reverse the anticoagulant effect make management of cases of over-anticoagulation challenging. CASE REPORT: In this case report an 87-year-old man with a history of atrial fibrillation presented with dabigatran excess in the setting of life-threatening, acute renal and hepatic failure. The authors review the use of dabigatran in elderly patients, the available data on management of patients with excess anticoagulation, and the potential options for reversal of the anticoagulation effect. CONCLUSION: Further investigation into reliable means of monitoring and reversing the anticoagulant effect of dabigatran is crucial to the management of such patients. PMID- 25135296 TI - VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells. AB - The focus of this study is the characterization of human T cell blood-brain barrier migration and corresponding molecular trafficking signatures. We examined peripheral blood and cerebrospinal fluid immune cells from patients under long term anti-very late antigen-4 (VLA-4)/natalizumab therapy (LTNT) and from CNS specimens. LTNT patients' cerebrospinal fluid T cells exhibited healthy central /effector-memory ratios, but lacked CD49d and showed enhanced myeloma cell adhesion molecule (MCAM) expression. LTNT led to an increase of PSGL-1 expression on peripheral T cells. Although vascular cell adhesion molecule-1 (VLA-4 receptor) was expressed at all CNS barriers, P-selectin (PSGL-1-receptor) was mainly detected at the choroid plexus. Accordingly, in vitro experiments under physiological flow conditions using primary human endothelial cells and LTNT patients' T cells showed increased PSGL-1-mediated rolling and residual adhesion, even under VLA-4 blockade. Adhesion of MCAM(+)/TH17 cells was not affected by VLA 4 blocking alone, but was abrogated when both VLA-4 and MCAM were inhibited. Consistent with these data, MCAM(+) cells were detected in white matter lesions, and in gray matter of multiple sclerosis patients. Our data indicate that lymphocyte trafficking into the CNS under VLA-4 blockade can occur by using the alternative adhesion molecules, PSGL-1 and MCAM, the latter representing an exclusive pathway for TH17 cells to migrate over the blood-brain barrier. PMID- 25135297 TI - Long-term survival of influenza virus infected club cells drives immunopathology. AB - Respiratory infection of influenza A virus (IAV) is frequently characterized by extensive immunopathology and proinflammatory signaling that can persist after virus clearance. In this report, we identify cells that become infected, but survive, acute influenza virus infection. We demonstrate that these cells, known as club cells, elicit a robust transcriptional response to virus infection, show increased interferon stimulation, and induce high levels of proinflammatory cytokines after successful viral clearance. Specific depletion of these surviving cells leads to a reduction in lung tissue damage associated with IAV infection. We propose a model in which infected, surviving club cells establish a proinflammatory environment aimed at controlling virus levels, but at the same time contribute to lung pathology. PMID- 25135298 TI - RUNX1-dependent RAG1 deposition instigates human TCR-delta locus rearrangement. AB - V(D)J recombination of TCR loci is regulated by chromatin accessibility to RAG1/2 proteins, rendering RAG1/2 targeting a potentially important regulator of lymphoid differentiation. We show that within the human TCR-alpha/delta locus, Ddelta2-Ddelta3 rearrangements occur at a very immature thymic, CD34(+)/CD1a( )/CD7(+dim) stage, before Ddelta2(Ddelta3)-Jdelta1 rearrangements. These strictly ordered rearrangements are regulated by mechanisms acting beyond chromatin accessibility. Importantly, direct Ddelta2-Jdelta1 rearrangements are prohibited by a B12/23 restriction and ordered human TCR-delta gene assembly requires RUNX1 protein, which binds to the Ddelta2-23RSS, interacts with RAG1, and enhances RAG1 deposition at this site. This RUNX1-mediated V(D)J recombinase targeting imposes the use of two Ddelta gene segments in human TCR-delta chains. Absence of this RUNX1 binding site in the homologous mouse Ddelta1-23RSS provides a molecular explanation for the lack of ordered TCR-delta gene assembly in mice and may underlie differences in early lymphoid differentiation between these species. PMID- 25135300 TI - Accumulation of adverse prognostic markers worsens prognosis in chronic lymphocytic leukaemia. PMID- 25135303 TI - Multi-component assembly and luminescence tuning of lanthanide hybrids based with both zeolite L/A and SBA-15 through two organically grafted linkers. AB - Both zeolite A/L and SBA-15 have been used to assemble novel photofunctional multi-component lanthanide hybrid materials. Microporous zeolites A/L are first functionalized by embedding lanthanide or zinc complexes (TTA = thenoyltrifluoroacetone, TAA = trifluoroacetone, bipy = 2,2'-bipyridyl) into the pores of zeolite A/L, and then the surface of functionalized zeolite A/L is modified via covalent linkers from aromatic carboxylic acids (para-aminobenzoic acid ABA and para-hydroxyl benzoic acid HBA) grafted by 3-(triethoxysilyl)-propyl isocyanate (TEPIC). On the other hand, SBA-15 is modified by grafting covalent linker phen-Si from the modification of 1,10-phenanthroline (phen) with TEPIC. Further, another lanthanide ion is used to link both functionalized zeolites, A/L and SBA-15, through the coordination with the two covalent linkers, ABS-Si (HBA Si) and phen-Si, respectively. Subsequently, the obtained multicomponent microporous-mesoporous hybrid materials are assembled and characterized using XRD, FT-IR, UV-vis DRS, SEM, TEM and luminescent approaches (spectra, lifetimes and quantum efficiencies). These hybrids with both microporous zeolite and SBA-15 mesoporous host possess favourable luminescent performance and some hybrid systems present the high quantum efficiencies of 90%. Besides, the luminescent color can be tuned by adjusting the composition of these hybrids, among which four hybrids (S-phen-Eu-HBA-[ZA-Tb-bipy], S-phen-Eu-HBA-[ZA-Zn-bipy], S-phen-Eu ABA-[ZA-Tb-TAA], S-phen-Eu-ABA-[ZL-Tb-bipy]) can be integrated to white light emission. PMID- 25135301 TI - Cannabis use by individuals with multiple sclerosis: effects on specific immune parameters. AB - Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS was similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naive cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective of Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study. PMID- 25135299 TI - Classical Flt3L-dependent dendritic cells control immunity to protein vaccine. AB - DCs are critical for initiating immunity. The current paradigm in vaccine biology is that DCs migrating from peripheral tissue and classical lymphoid-resident DCs (cDCs) cooperate in the draining LNs to initiate priming and proliferation of T cells. Here, we observe subcutaneous immunity is Fms-like tyrosine kinase 3 ligand (Flt3L) dependent. Flt3L is rapidly secreted after immunization; Flt3 deletion reduces T cell responses by 50%. Flt3L enhances global T cell and humoral immunity as well as both the numbers and antigen capture capacity of migratory DCs (migDCs) and LN-resident cDCs. Surprisingly, however, we find immunity is controlled by cDCs and actively tempered in vivo by migDCs. Deletion of Langerin(+) DC or blockade of DC migration improves immunity. Consistent with an immune-regulatory role, transcriptomic analyses reveals different skin migDC subsets in both mouse and human cluster together, and share immune-suppressing gene expression and regulatory pathways. These data reveal that protective immunity to protein vaccines is controlled by Flt3L-dependent, LN-resident cDCs. PMID- 25135304 TI - Occurrence of hemocyanin in ostracod crustaceans. AB - Hemocyanin is a copper-containing protein that transports O2 in the hemolymph of many arthropod species. Within the crustaceans, hemocyanin appeared to be restricted to Malacostraca but has recently been identified in Remipedia. Here, we report the occurrence of hemocyanin in ostracods, indicating that this respiratory protein is more widespread within crustaceans than previously thought. By analyses of expressed sequence tags and by RT-PCR, we obtained four full length and nine partial hemocyanin sequences from six of ten investigated ostracod species. Hemocyanin was identified in Myodocopida (Actinoseta jonesi, Cypridininae sp., Euphilomedes morini, Skogsbergia lerneri, Vargula tsujii) and Platycopida (Cytherelloidea californica) but not in Podocopida. We found no evidence for the presence of hemoglobin in any of these ostracod species. Like in other arthropods, we identified multiple hemocyanin subunits (up to six) to occur in a single ostracod species. Bayesian phylogenetic analyses showed that ostracod hemocyanin subunit diversity evolved independently from that of other crustaceans. Ostracod hemocyanin subunits were found paraphyletic, with myodocopid and platycopid subunits forming distinct clades within those of the crustaceans. This pattern suggests that ostracod hemocyanins originated from distinct subunits in the pancrustacean stemline. PMID- 25135302 TI - Immunization with P10 peptide increases specific immunity and protects immunosuppressed BALB/c mice infected with virulent yeasts of Paracoccidioides brasiliensis. AB - Paracoccidioidomycosis is a systemic granulomatous disease caused by Paracoccidioides spp. A peptide from the major diagnostic antigen gp43, named P10, induces a T-CD4(+) helper-1 immune response in mice and protects against intratracheal challenge with virulent P. brasiliensis. Previously, we evaluated the efficacy of the P10 peptide alone or combined with antifungal drugs in mice immunosuppressed and infected with virulent isolate of P. brasiliensis. In the present work, our data suggest that P10 immunization leads to an effective cellular immune response associated with an enhanced T cell proliferative response. P10-stimulated splenocytes increased nitric oxide (NO) production and induced high levels of IFN-gamma, IL-1beta and IL-12. Furthermore, significantly increased concentrations of pro-inflammatory cytokines were also observed in lung homogenates of immunized mice. P10 immunization was followed by minimal fibrosis in response to infection. Combined with antifungal drugs, P10 immunization most significantly improved survival of anergic infected mice. Administration of either itraconazole or sulfamethoxazole/trimethoprim together with P10 immunization resulted in 100 % survival up to 200 days post-infection, whereas untreated mice died within 80 days. Hence, our data show that P10 immunization promotes a strong specific immune response even in immunocompromised hosts and thus P10 treatment represents a powerful adjuvant therapy to chemotherapy. PMID- 25135306 TI - Unusual phenomena in the reduction process of vanadium(v) on a graphite electrode at high overpotentials. AB - An abrupt increase in the Tafel slope and the charge transfer resistance (Rct) of V(v) ions on a graphite electrode are both observed at a transition potential (EK). The possible vanadium complexes such as V2O3(3+) might result in the change of reduction mechanism and the unusual phenomena. PMID- 25135305 TI - Melatonin and oestrogen treatments were able to improve neuroinflammation and apoptotic processes in dentate gyrus of old ovariectomized female rats. AB - The aim of this study was to determine the outcomes of oestrogen and melatonin treatments following long-term ovarian hormone depletion on neuroinflammation and apoptotic processes in dentate gyrus of hippocampi. Forty-six female Wistar rats of 22 months of age were used. Twelve of them remained intact, and the other 34 were ovariectomized at 12 months of age. Ovariectomized animals were divided into three groups and treated for 10 weeks with oestrogens, melatonin or saline. All rats were killed by decapitation at 24 months of age, and dentate gyri were collected. A group of 2 month-old intact female rats was used as young control. The levels of pro-inflammatory cytokines and heat shock protein 70 (HSP 70) were analysed by ELISA. The expressions of TNFalpha, IL1beta, GFAP, nNOS, iNOS, HO-1, NFkappaB, Bax, Bad, AIF, Bcl2 and SIRT1 genes were detected by real-time (RT) PCR. Western blots were used to measure the protein expression of NFkappaB p65, NFkappaB p50/105, IkappaBalpha, IkappaBbeta, p38 MAPK, MAP-2 and synapsin I. We have assessed the ability of 17beta-oestradiol and melatonin administration to downregulate markers of neuroinflammation in the dentate gyrus of ovariectomized female rats. Results indicated that 17beta-oestradiol and melatonin treatments were able to significantly decrease expression of pro-inflammatory cytokines, iNOS and HO-1 in the hippocampus when compared to non-treated animals. A similar age- and long-term ovarian hormone depletion- related increase in GFAP was also attenuated after both melatonin and oestradiol treatments. In a similar way to oestradiol, melatonin decreased the activation of p38 MAPK and NFkappaB pathways. The treatments enhanced the levels of synaptic molecules synapsin I and MAP-2 and have been shown to modulate the pro-antiapoptotic ratio favouring the second and to increase SIRT1 expression. These findings support the potential therapeutic role of melatonin and oestradiol as protective anti-inflammatory agents for the central nervous system during menopause. PMID- 25135307 TI - An electrically switchable metal-organic framework. AB - Crystalline metal organic framework (MOF) materials containing interconnected porosity can be chemically modified to promote stimulus-driven (light, magnetic or electric fields) structural transformations that can be used in a number of devices. Innovative research strategies are now focused on understanding the role of chemical bond manipulation to reversibly alter the free volume in such structures of critical importance for electro-catalysis, molecular electronics, energy storage technologies, sensor devices and smart membranes. In this letter, we study the mechanism for which an electrically switchable MOF composed of Cu(TCNQ) (TCNQ = 7,7,8,8-tetracyanoquinodimethane) transitions from a high resistance state to a conducting state in a reversible fashion by an applied potential. The actual mechanism for this reversible electrical switching is still not understood even though a number of reports are available describing the application of electric-field-induced switching of Cu(TCNQ) in device fabrication. PMID- 25135308 TI - The virtual toxicology service: wearable head-mounted devices for medical toxicology. PMID- 25135309 TI - Coming to a consensus on informed consent for case reports. PMID- 25135311 TI - The S curve: a novel morphological finding in the internal carotid artery in patients with fibromuscular dysplasia. AB - Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease commonly affecting the renal and internal carotid arteries (ICAs). A previously unrecognized finding is a redundancy of the mid-distal ICA in FMD patients causing an 'S'-shaped curve. Carotid artery duplex ultrasounds were reviewed in 116 FMD patients to determine S-curve prevalence. FMD patients with an S curve were matched to four control patients divided equally into two groups: (1) age and sex-matched and (2) age >=70 and sex-matched. S curves were present in 37 (32%) FMD patients. Of these, nine (24%) had angiographic evidence of FMD in their ICA only, 13 (35%) had renal artery FMD only, and 15 (41%) had both ICA and renal FMD. Two patients in the age and sex-matched group had S curves (odds ratio 16.86, 95% CI 3.92-72.48; p<0.0001) while 12 (16.2%) patients in the age >=70 and sex-matched group had S curves (odds ratio 2.42, 95% CI 1.16-5.03; p=0.016). In conclusion, the S curve is a novel morphological pattern of the mid-distal ICA. While the S curve may not be specific, its presence in individuals <70 years old should alert the clinician to the possibility that FMD is present. PMID- 25135310 TI - Multi-centre analysis of incidental findings on low-resolution CT attenuation correction images. AB - OBJECTIVE: To review new incidental findings detected on low-resolution CT attenuation correction (CTAC) images acquired during single-photon emission CT (SPECT-CT) myocardial perfusion imaging (MPI) and to determine whether the CTAC images had diagnostic value and warrant reporting. METHODS: A multicentre study was performed in four UK nuclear medicine departments. CTAC images acquired as part of MPI performed using SPECT were evaluated to identify incidental findings. New findings considered to be clinically significant were evaluated further. Positive predictive value (PPV) was determined at the time of definitive diagnosis. RESULTS: Of 1819 patients studied, 497 (27.3%) had a positive CTAC finding. 51 (2.8%) patients had findings that were clinically significant at the time of the CTAC report and had not been previously diagnosed. Only four (0.2%) of these were potentially detrimental to patient outcome. CONCLUSION: One centre had a PPV of 0%, and the study suggests that these CTAC images should not be reported. Two centres with more modern equipment had low PPVs of 0% and 6%, respectively, and further research is suggested prior to drawing a conclusion. The centre with best quality CT had a PPV of 67%, and the study suggests that CTAC images from this equipment should be reported. ADVANCES IN KNOWLEDGE: This study is unique compared with previous studies that have reported only the potential to identify incidental findings on low-resolution CT images. This study both identifies and evaluates new clinically significant incidental findings, and it demonstrates that the benefit of reporting the CTAC images depends on the type of equipment used. PMID- 25135313 TI - Kinetics of nitrification in a fixed biofilm reactor using dewatered sludge-fly ash composite ceramic particle as a supporting medium. AB - A mathematical model system was derived to describe the kinetics of ammonium nitrification in a fixed biofilm reactor using dewatered sludge-fly ash composite ceramic particle as a supporting medium. The model incorporates diffusive mass transport and Monod kinetics. The model was solved using a combination of the orthogonal collocation method and Gear's method. A batch test was conducted to observe the nitrification of ammonium-nitrogen ([Formula: see text]-N) and the growth of nitrifying biomass. The compositions of nitrifying bacterial community in the batch kinetic test were analyzed using PCR-DGGE method. The experimental results show that the most staining intensity abundance of bands occurred on day 2.75 with the highest biomass concentration of 46.5 mg/L. Chemostat kinetic tests were performed independently to evaluate the biokinetic parameters used in the model prediction. In the column test, the removal efficiency of [Formula: see text]-N was approximately 96 % while the concentration of suspended nitrifying biomass was approximately 16 mg VSS/L and model-predicted biofilm thickness reached up to 0.21 cm in the steady state. The profiles of denaturing gradient gel electrophoresis (DGGE) of different microbial communities demonstrated that indigenous nitrifying bacteria (Nitrospira and Nitrobacter) existed and were the dominant species in the fixed biofilm process. PMID- 25135312 TI - Arachnoid membrane: the first and probably the last piece of the roadmap. AB - Most neurosurgical procedures could be performed noninvasively by working through the natural corridors provided by the subarachnoid cisterns. In consequence, the subarachnoid cisterns have been considered as the roadmaps for the microneurosurgeons. The concept and the contents of the cisterns have been well known and described, but the knowledge of the detailed anatomy of the arachnoid membranes, which are the real septa of the cisterns and provide the practical and important landmarks and planes for the dissections during the brain surgeries, is still lacking. The present article reviews the previous reports of the intracranial arachnoid membranes with a special emphasis on the microsurgical anatomy and the clinical significance. PMID- 25135314 TI - Microrespirometric characterization of activated sludge inhibition by copper and zinc. AB - We have developed a novel microrespirometric method to characterize the inhibitory effects due to heavy metals on activated sludge treatment. This method was based on pulse dynamic respirometry and involved the injection of several pulses of substrate and inhibitors, of increasing concentration. Furthermore, we evaluated the inhibitory effects of heavy metals (copper and zinc), substrate and biomass concentrations, and pH on activated sludge activity. While higher biomass concentrations counteracted the inhibitory effects of both copper and zinc, higher substrate concentrations predominantly augmented the inhibitory effect of copper but no significant change in inhibition by zinc was observed. pH had a clear but relatively small effect on inhibition, partially explained by thermodynamic speciation. We determined the key kinetic parameters; namely, the half saturation constant (K S ) and the maximum oxygen uptake rate (OUR max ). The results showed that higher heavy metal concentrations substantially decreased K S and OUR max suggesting that the inhibition was uncompetitive. PMID- 25135315 TI - Enhanced production of 2,3-butanediol by a genetically engineered Bacillus sp. BRC1 using a hydrolysate of empty palm fruit bunches. AB - A Bacillus species that produces 2,3-butanediol (2,3-BD), termed BRC1, was newly isolated, and a 2,3-BD dehydrogenase (Bdh) from this species was identified and characterized at the molecular and biochemical level. Sequence analysis revealed that Bdh is homologous to D-2,3-BD dehydrogenases. An analysis of the enzymatic properties of Bdh overexpressed in Escherichia coli confirmed the molecular results, showing preferred activity toward D-2,3-BD. Optimum pH, temperature, and kinetics determined for reductive and oxidative reactions support the preferential production of 2,3-BD during cell growth. Overexpression of bdh under the control of a xylose-inducible promoter resulted in increased enzyme activity and enhanced 2,3-BD production in Bacillus sp. BRC1. Additionally, a hydrolysate of cellulosic material, (empty palm fruit bunches), was successfully used for the enhanced production of 2,3-BD in the recombinant Bacillus strain. PMID- 25135316 TI - Assessment of metal artefact reduction around dental titanium implants in cone beam CT. AB - OBJECTIVES: The aim of this study was to investigate if the metal artefact reduction (MAR) tool used in the software of the ORTHOPANTOMOGRAPH((r)) OP300 (Instrumentarium Dental, Tuusula, Finland) can improve the gray value levels in post-operative implant scans. METHODS: 20 potential implant sites were selected from 5 edentulous human dry mandibles. Each mandible was scanned by a CBCT scanner, and images were produced under three different conditions: implant sites drilled but no implants inserted, implants inserted without application of MAR and implants inserted with application of MAR. Using Geomagic((r)) Studio 2012 (Geomagic, Morrisville, NC) and 3Diagnosys((r)) v. 5.3.1 (3Diemme((r)) SRL, Cantu, Italy) software, three scans of each mandible were superimposed. The mean gray value of identical regions of bone around the implants was derived for each condition. The differences between gray value measurements at implant sites derived from different conditions were assessed. RESULTS: A significant difference was found between mean gray values from the scans with no implants inserted and with implants inserted (with and without MAR) (p = 0.012). No significant difference was revealed for gray values measured from scans with and without MAR (p = 0.975). CONCLUSIONS: The MAR tool in the software of the ORTHOPANTOMOGRAPH OP300 CBCT scanner does not significantly correct the voxel gray values affected by the metal artefact in the vicinity of an implant in human dry mandibles. PMID- 25135318 TI - Preaggregated Ag nanoparticles in dry swellable gel films for off-the-shelf surface-enhanced Raman spectroscopy. AB - Large, thin (50 MUm) dry polymer sheets containing numerous surface-enhanced Raman spectroscopy (SERS) active Ag nanoparticle aggregates have been prepared by drying aqueous mixtures of hydroxyethylcelloulose (HEC) and preaggregated Ag colloid in 10 * 10 cm molds. In these dry films, the particle aggregates are protected from the environment during storage and are easy to handle; for example, they can be cut to size with scissors. When in use, the highly swellable HEC polymer allowed the films to rapidly absorb aqueous analyte solutions while simultaneously releasing the Ag nanoparticle aggregates to interact with the analyte and generate large SERS signals. Either the films could be immersed in the analyte solution or 5 MUL droplets were applied to the surface; in the latter method, the local swelling caused the active area to dome upward, but the swollen film remained physically robust and could be handled as required. Importantly, encapsulation and release did not significantly compromise the SERS performance of the colloid; the signals given by the swollen films were similar to the very high signals obtained from the parent citrate-reduced colloid and were an order of magnitude larger than a commercially available nanoparticle substrate. These "Poly-SERS" films retained 70% of their SERS activity after being stored for 1 year in air. The films were sufficiently homogeneous to give a standard deviation of 3.2% in the absolute signal levels obtained from a test analyte, primarily due to the films' ability to suppress "coffee ring" drying marks, which meant that quantitative analysis without an internal standard was possible. The majority of the work used aqueous thiophenol as the test analyte; however, preliminary studies showed that the Poly-SERS films could also be used with nonaqueous solvents and for a range of other analytes including theophylline, a therapeutic drug, at a concentration as low as 1.0 * 10(-5) mol dm(-3) (1.8 mg/dm(3)), well below the sensitivity required for theophylline monitoring where the target range is 10-20 mg/dm(3). PMID- 25135317 TI - Efficacy of CBCT for assessment of impacted mandibular third molars: a review - based on a hierarchical model of evidence. AB - A radiographic examination of mandibular third molars is meant to support the surgeon in establishing a treatment plan. For years panoramic (PAN) imaging has been the first choice method; however, where an overprojection is observed between the third molar and the mandibular canal and when specific signs suggest a close contact between the molar and the canal, CBCT may be indicated. The present review provides an evaluation of the efficacy of CBCT for assessment of mandibular third molars using a six-tiered hierarchical model by Fryback and Thornbury in 1991. Levels 1-3 include studies on low evidence levels mainly regarding the technical capabilities of a radiographic method and the diagnostic accuracy of the related images. Levels 4-6 include studies on a higher level of evidence and assess the diagnostic impact of a radiographic method on the treatment of the patient in addition to the outcome for the patient and society including cost calculations. Only very few high-evidence studies on the efficacy of CBCT for radiographic examination of mandibular third molars exist and, in conclusion, periapical or PAN examination is sufficient in most cases before removal of mandibular third molars. However, CBCT may be suggested when one or more signs for a close contact between the tooth and the canal are present in the two-dimensional image-if it is believed that CBCT will change the treatment or the treatment outcome for the patient. Further research on high-evidence levels is needed. PMID- 25135319 TI - Bioinspired microfluidic assay for in vitro modeling of leukocyte-endothelium interactions. AB - Current in vitro models of the leukocyte adhesion cascade cannot be used for real time studies of the entire leukocyte adhesion cascade, including rolling, adhesion, and migration in a single assay. In this study, we have developed and validated a novel bioinspired microfluidic assay (bMFA) and used it to test the hypothesis that blocking of specific steps in the adhesion/migration cascade significantly affects other steps of the cascade. The bMFA consists of an endothelialized microvascular network in communication with a tissue compartment via a 3 MUm porous barrier. Human neutrophils in bMFA preferentially adhered to activated human endothelial cells near bifurcations with rolling and adhesion patterns in close agreement with in vivo observations. Treating endothelial cells with monoclonal antibodies to E-selectin or ICAM-1 or treating neutrophils with wortmannin reduced rolling, adhesion, and migration of neutrophils to 60%, 20%, and 18% of their respective control values. Antibody blocking of specific steps in the adhesion/migration cascade (e.g., mAb to E-selectin) significantly downregulated other steps of the cascade (e.g., migration). This novel in vitro assay provides a realistic human cell based model for basic science studies, identification of new treatment targets, selection of pathways to target validation, and rapid screening of candidate agents. PMID- 25135321 TI - Health related quality of life is differently associated with leisure-time physical activity intensities according to gender: a cross-sectional approach. AB - BACKGROUND: Several studies have demonstrated a positive association between physical activity (PA) and health-related quality of life (HRQL). However, studies have suggested that this association depends both on the PA intensity and the domain of HRQL evaluated. This study aimed to explore the association between physical, mental and overall HRQL with recommended levels of PA. PA levels were divided into moderate and vigorous intensity leisure-time PA and total leisure time PA. METHODS: The study included 1001 adults, 582 women (46 +/- 17 years) and 419 men (43 +/- 16 years), residents in Rio Claro-SP, Brazil. All participants completed the SF-36 questionnaire to assess HRQL and the long version of the International Physical Activity Questionnaire (IPAQ) to assess level and intensities of leisure-time PA. Total leisure-time PA at moderate intensity was classified as: less than 9 min/week, 10-149 min/week, 150-299 min/week and 300 min/week or more. Total leisure-time PA at vigorous intensity was classified as: less than 9 min/week, 10 to 74.9 min/week, 75-149 min/week and 150 min/week or more. Multiple linear regression was performed in STATA version 12.0. RESULTS: Among women, moderate intensity and total leisure-time PA were associated with physical health. Among men, moderate and vigorous intensity and total leisure time PA were associated with physical health and overall HRQL. Furthermore, moderate intensity and total leisure-time PA were associated with mental health in men. However, vigorous intensity PA was not associated with mental health for this group. CONCLUSION: The different domains of HRQL were associated with different levels and intensities of PA in leisure-time according to gender of adults. These findings indicate the complexity and importance of evaluating the HRQL stratified by gender and consider the different levels and intensities of PA. PMID- 25135320 TI - Development of phage immuno-loop-mediated isothermal amplification assays for organophosphorus pesticides in agro-products. AB - Two immuno-loop-mediated isothermal amplification assays (iLAMP) were developed by using a phage-borne peptide that was isolated from a cyclic eight-peptide phage library. One assay was used to screen eight organophosphorus (OP) pesticides with limits of detection (LOD) between 2 and 128 ng mL(-1). The iLAMP consisted of the competitive immuno-reaction coupled to the LAMP reaction for detection. This method provides positive results in the visual color of violet, while a negative response results in a sky blue color; therefore, the iLAMP allows one to rapidly detect analytes in yes or no fashion. We validated the iLAMP by detecting parathion-methyl, parathion, and fenitrothion in Chinese cabbage, apple, and greengrocery, and the detection results were consistent with the enzyme-linked immunosorbent assay (ELISA). In conclusion, the iLAMP is a simple, rapid, sensitive, and economical method for detecting OP pesticide residues in agro-products with no instrumental requirement. PMID- 25135322 TI - A high-throughput sequencing ecotoxicology study of freshwater bacterial communities and their responses to tebuconazole. AB - The pollution of lakes and rivers by pesticides is a growing problem worldwide. However, the impacts of these substances on microbial communities are still poorly understood, partly because next-generation sequencing (NGS) has rarely been used in an ecotoxicology context to study bacterial communities despite its interest for accessing rare taxa. Microcosm experiments were carried out to evaluate the effects of tebuconazole (TBZ) on the structure and composition of bacterial communities from two types of freshwater ecosystem (lakes and rivers) with differing histories of pollutant contamination (pristine vs. previously exposed sites). Pyrosequencing revealed that bacterial diversity was higher in the river than in the lakes and in previously exposed sites than in pristine sites. Lakes and river stations shared very few OTUs, and differences at the phylum level were identified between these ecosystems (i.e. the relative importance of Actinobacteria and Gammaproteobacteria). Despite differences between these ecosystems and their contamination history, no significant effect of TBZ on bacterial community structure or composition was observed. Compared to functional parameters that displayed variable responses, we demonstrated that a combination of classical methods and NGS is necessary to investigate the ecotoxicological responses of microbial communities to pollutants. PMID- 25135324 TI - Smaller pupil size and better proofreading performance with positive than with negative polarity displays. AB - The 'positive polarity advantage' describes the fact that reading performance is better for dark text on light background (positive polarity) than for light text on dark background (negative polarity). We investigated the underlying mechanism by assessing pupil size and proofreading performance when reading positive and negative polarity texts. In particular, we tested the display luminance hypothesis which postulates that the typically greater brightness of positive compared to negative polarity displays leads to smaller pupil sizes and, hence, a sharper retinal image and better perception of detail. Indeed, pupil sizes were smaller and proofreading performance was better with positive than with negative polarity displays. The results are compatible with the hypothesis that the positive polarity advantage is an effect of display luminance. Limitations of the study are being discussed. PMID- 25135323 TI - Serum lipid concentrations in patients with cholesterol and pigment gallstones. AB - BACKGROUND: Gallstones (GS) are formed as a result of impaired metabolic regulation of the human body. Abnormal lipid metabolism is partly responsible for the pathogenesis of GS mainly rich in cholesterol. Thus abnormalities of serum lipids would reflect the possibilities of the formation of cholesterol GS. This study aims to identify the significance of serum lipids on the development of GS disease. METHODS: Serum lipid profiles were estimated in 73 patients with symptomatic GS, admitted to the Teaching Hospital, Peradeniya, Sri Lanka for GS removal surgeries from May 2011 to December 2012. Patients with normal serum bilirubin level and not being on lipid lowering drugs were recruited for the study. Serum lipid profile of each patient was analyzed by enzymatic kit assays and the chemical composition of GS was analyzed by Fourier Transform Infrared spectroscopy. RESULTS: Of the 73 patients, 37 (51%) had cholesterol GS while 36 (49%) had pigment GS. Serum lipid parameters of a majority of patients were within the normal range. Body mass index values of the patients with two types of GS were not significantly different (Two sample t test, p = 0.335). Out of the lipid parameters tested, only serum triglyceride concentration was significantly high in patients with cholesterol GS than that of pigment GS (Two sample t test, p = 0.038). None of the lipid parameters were significantly different between males and females (Two sample t test, p > 0.05). Compared to the patients with pigment GS who were aged below 50 years, mean total cholesterol and triglyceride concentrations were higher in the same age category patients with cholesterol GS. CONCLUSION: Abnormal serum lipid profiles doesn't seem to be an essential feature in patients with cholesterol GS. However when the two groups of patients with cholesterol and pigment GS with no significant difference of body mass indexes were compared, patients with cholesterol GS are more likely to have serum lipid parameters towards the undesirable cutoff levels of their respective normal ranges. However an effect of serum lipid concentrations on high incidence of GS among females has not been identified. PMID- 25135325 TI - A novel wheat bZIP transcription factor, TabZIP60, confers multiple abiotic stress tolerances in transgenic Arabidopsis. AB - The basic region/leucine zipper (bZIP) transcription factors (TFs) play vital roles in the response to abiotic stress. However, little is known about the function of bZIP genes in wheat abiotic stress. In this study, we report the isolation and functional characterization of the TabZIP60 gene. Three homologous genome sequences of TabZIP60 were isolated from hexaploid wheat and mapped to the wheat homoeologous group 6. A subcellular localization analysis indicated that TabZIP60 is a nuclear-localized protein that activates transcription. Furthermore, TabZIP60 gene transcripts were strongly induced by polyethylene glycol, salt, cold and exogenous abscisic acid (ABA) treatments. Further analysis showed that the overexpression of TabZIP60 in Arabidopsis resulted in significantly improved tolerances to drought, salt, freezing stresses and increased plant sensitivity to ABA in seedling growth. Meanwhile, the TabZIP60 was capable of binding ABA-responsive cis-elements that are present in promoters of many known ABA-responsive genes. A subsequent analysis showed that the overexpression of TabZIP60 led to enhanced expression levels of some stress responsive genes and changes in several physiological parameters. Taken together, these results suggest that TabZIP60 enhances multiple abiotic stresses through the ABA signaling pathway and that modifications of its expression may improve multiple stress tolerances in crop plants. PMID- 25135326 TI - The medium term prognostic value of dobutamine stress echocardiogram in patients with high risk scores of coronary artery disease according to NICE Clinical Guideline 95. PMID- 25135327 TI - Melioidosis: a rare cause of constrictive pericarditis. PMID- 25135328 TI - Rosuvastatin treatment improves arterial stiffness with lowering blood pressure in healthy hypercholesterolemic patients. PMID- 25135329 TI - Transcatheter Amplatzer Duct Occluder II closure of perimembranous ventricular septal defect with right lung agenesis. PMID- 25135330 TI - The role of angioplasty in patients with acute coronary syndrome and previous coronary artery bypass grafting. AB - INTRODUCTION: Angioplasty has changed the management of acute coronary syndrome (ACS). However, in patients with previous coronary artery bypass grafting (CABG), the role of angioplasty in the management of ACS is widely debated. Lack of clear guidelines leads to subjective and often stereotypical assessments based on clinician preferences. We sought to investigate if angioplasty affected all cause mortality in ACS patients with previous CABG. METHODS: Completely anonymous information on patients with ACS with a background of previous CABG, co morbidities and procedures attending three multi-ethnic general hospitals in the North West of England, United Kingdom in the period 2000-2012 was traced using the ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) study protocol using ICD-10 and OPCS-4 coding systems. Predictors of mortality and survival analyses were performed using SPSS version 20.0. RESULTS: Out of 12,227 patients with ACS, there were 1172 (19.0%) cases of ACS in patients with previous coronary artery bypass grafting. Of these 83 (7.1%) patients underwent angioplasty. Multi-nominal logistic regression, accounting for differences in age and co-morbidities, revealed that having angioplasty conferred a 7.96 times improvement in mortality (2.36-26.83 95% CI) compared to not having angioplasty in this patient group. CONCLUSIONS: We have shown that angioplasty confers significantly improved all cause mortality in the management of ACS in patients with previous CABG. The findings of this study highlight the need for clinicians to conscientiously think about the individual benefits and risks of angioplasty for every patient rather than confining to age related stereotypes. PMID- 25135331 TI - Astragali Radix protects myocardium from ischemia injury by modulating energy metabolism. PMID- 25135332 TI - Wolff-Parkinson-White syndrome influenced by myocardial infarction? PMID- 25135333 TI - Exercise ventilatory power in heart failure patients: functional phenotypes definition by combining cardiopulmonary exercise testing with stress echocardiography. PMID- 25135334 TI - No clear evidence of a clinical benefit of a sequential therapy regimen with abiraterone acetate and enzalutamide. AB - Prostate cancer is the second leading cause of cancer-related deaths in men in most western countries. New agents for metastatic castration-resistant prostate cancer (CRPC) developed in the past 3 years include abiraterone acetate (AA) and enzalutamide (ENZ), which inhibit signaling by and synthesis of androgens, respectively. Because they share the same target, potential clinical cross resistance between AA and E is possible. In this review, we discuss the results of clinical studies in which CRPC patients were treated with AA and E either separately or in sequence after first-line treatment with docetaxel. Our review suggests that sequential administration of AA and E in either order has limited activity after docetaxel therapy. Prospective studies that further examine sequential treatments with AA and E are warranted. PMID- 25135335 TI - A.S.P.E.N. data brief 2014: use of enteral and parenteral nutrition in hospitalized patients with a diagnosis of malnutrition: United States, 2010. PMID- 25135337 TI - Hospital-based study of dental pathology and faecal particle size distribution in horses with large colon impaction. AB - The aim of the study was to determine if horses with large colon impaction were more severely affected by oral pathology than control cases and to relate faecal particle size distribution to dental pathology in both study groups. A prospective study included 39 horses with large colon impaction and 72 control horses from a hospital-based population. An oral pathology score (OPscore) and periodontal disease index (PDI) were assigned to all horses and faecal samples were collected for estimating faecal particle size and analysis of particle size distribution. Horses with large colon impactions were not more severely affected by oral pathology than control horses for both OPscore (P = 0.2) and PDI (P = 0.3). Faecal particle size estimates were significantly higher in control animals (P <0.001). No significant association was found between faecal particle size estimates and OPscores in horses with large colon impaction or control horses. In horses with large colon impaction, faecal particle size estimates increased with increasing PDI (P = 0.05). No associations were found between dental pathology and faecal particle size estimates. Horses developing large colon impaction did not have worse dentition than control horses. PMID- 25135338 TI - The pharmacokinetics and in vitro/ex vivo cyclooxygenase selectivity of parecoxib and its active metabolite valdecoxib in cats. AB - Parecoxib (PX) is an injectable prodrug of valdecoxib (VX, which is a selective cyclo-oxyganase-2 (COX-2)) inhibitor licensed for humans. The aim of the present study was to evaluate pharmacokinetics and in vitro/ex vivo cyclooxygenase selectivity of PX and VX in cats. In a whole blood in vitro study, PX did not affect either COX enzymes whereas VX revealed a COX-2 selective inhibitory effect in feline whole blood. The IC50 values of VX for COX-2 and COX-1 were 0.45 and 38.6 uM, respectively. Six male cats were treated with 2.5 mg/kg of PX by intramuscular injection. PX was rapidly converted to VX with a relatively short half-life of 0.4 h. VX achieved peak plasma concentration (2.79 +/- 1.59 ug/mL) at 7 h following PX injection. The mean residence times for PX and VX were 0.43 +/- 0.15 and 5.94 +/- 0.88 h, respectively. In the ex vivo study, PX showed a COX 2 inhibition rate of about 70% in samples taken at 1, 2, 4 and 10 h after injection, with a significant difference compared to the control. In contrast, COX-1 was slightly inhibited, ranging from 0.7% to 9.7% of the control inhibition rate without any significant difference for 24 h after PX administration. The preliminary findings of the present research appear promising and encourage further studies to investigate whether PX can be successfully used in feline medicine. PMID- 25135340 TI - Experimental infection of highly pathogenic avian influenza virus H5N1 in black headed gulls (Chroicocephalus ridibundus). AB - Historically, highly pathogenic avian influenza viruses (HPAIV) rarely resulted in infection or clinical disease in wild birds. However, since 2002, disease and mortality from natural HPAIV H5N1 infection have been observed in wild birds including gulls. We performed an experimental HPAIV H5N1 infection of black headed gulls (Chroicocephalus ridibundus) to determine their susceptibility to infection and disease from this virus, pattern of viral shedding, clinical signs, pathological changes and viral tissue distribution. We inoculated sixteen black headed gulls with 1 * 10(4) median tissue culture infectious dose HPAIV H5N1 (A/turkey/Turkey/1/2005) intratracheally and intraesophageally. Birds were monitored daily until 12 days post inoculation (dpi). Oropharyngeal and cloacal swabs were collected daily to detect viral shedding. Necropsies from birds were performed at 2, 4, 5, 6, 7, and 12 dpi. Sampling from selected tissues was done for histopathology, immunohistochemical detection of viral antigen, PCR, and viral isolation. Our study shows that all inoculated birds were productively infected, developed systemic disease, and had a high morbidity and mortality rate. Virus was detected mainly in the respiratory tract on the first days after inoculation, and then concentrated more in pancreas and central nervous system from 4 dpi onwards. Birds shed infectious virus until 7 dpi from the pharynx and 6 dpi from the cloaca. We conclude that black-headed gulls are highly susceptible to disease with a high mortality rate and are thus more likely to act as sentinel species for the presence of the virus than as long-distance carriers of the virus to new geographical areas. PMID- 25135339 TI - Detection of antibodies against porcine epidemic diarrhea virus in serum and colostrum by indirect ELISA. AB - An indirect porcine epidemic diarrhea virus (PEDV) anti-immunoglobulin (Ig) G ELISA based on the S1 portion of the spike protein was validated and compared with an indirect immunofluorescence assay. In serum samples from experimentally infected pigs (n = 35), anti-IgG PEDV antibodies were detected as early as 7 days post-infection. In field serum samples (n = 239), the diagnostic sensitivity of the S1 ELISA was 100% and the diagnostic specificity was 94%. The S1 ELISA showed no cross-reactivity with antibodies against other porcine coronaviruses. Colostrum samples (n = 133) were also tested for anti-PEDV IgG and IgA. The diagnostic sensitivity was 92% for IgG and 100% for IgA, and the diagnostic specificity was 90% for IgG and 99.4% for IgA. These data suggest that the S1 ELISA is a sensitive and specific test that could also be used to evaluate PEDV colostral immunity. PMID- 25135336 TI - Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36. AB - Neuronal gap junction (GJ) channels composed of connexin36 (Cx36) play an important role in neuronal synchronization and network dynamics. Here we show that Cx36-containing electrical synapses between inhibitory neurons of the thalamic reticular nucleus are bidirectionally modulated by changes in intracellular free magnesium concentration ([Mg(2+)]i). Chimeragenesis demonstrates that the first extracellular loop of Cx36 contains a Mg(2+) sensitive domain, and site-directed mutagenesis shows that the pore-lining residue D47 is critical in determining high Mg(2+)-sensitivity. Single-channel analysis of Mg(2+)-sensitive chimeras and mutants reveals that [Mg(2+)]i controls the strength of electrical coupling mostly via gating mechanisms. In addition, asymmetric transjunctional [Mg(2+)]i induces strong instantaneous rectification, providing a novel mechanism for electrical rectification in homotypic Cx36 GJs. We suggest that Mg(2+)-dependent synaptic plasticity of Cx36-containing electrical synapses could underlie neuronal circuit reconfiguration via changes in brain energy metabolism that affects neuronal levels of intracellular ATP and [Mg(2+)]i. PMID- 25135341 TI - FoxO1 at the nexus between fat catabolism and longevity pathways. AB - Adipose tissue should not be considered a simple fat sink but a specialized system that promptly and dynamically responds to variations of nutrients, to fulfil its major role in whole-body energy homeostasis. Perturbation of energy storage and utilization, as well as the expansion of adipose tissue during ageing, are hallmarks of several inflammation-related metabolic disorders. Studies using model organisms have provided significant insight into the genetic factors and environmental conditions that influence adipose tissue function and cause the failure of its homeostasis. It is now clear that reduced caloric intake has a major impact on adipose tissue function and can provide a path towards better health and the avoidance of age-related chronic diseases. An intricate and evolutionary conserved signalling network is necessary to manage adipocyte response to nutrients. The transcription factor FoxO1 plays a leading role in integrating dietary conditions, insulin signalling and the down-stream response of adipocytes to maintain metabolic balance. Here we review recent insights on the novel role of FoxO1 in regulating lipid catabolism through the induction of adipose triglyceride lipase (ATGL) and lysosomal lipase (Lipa) in adipocytes during nutrient restriction. In particular, we highlight the nutrient-sensing and hormone-independent feature of FoxO1 activity and illustrate how, by potentiating lipid breakdown, the FoxO1 signalling cascade could induce pro-longevity adaptive responses in adipose tissue. PMID- 25135342 TI - Development and characterization of a hydrogel containing nitrofurazone for antimicrobial topical applications. AB - The goal of the research work entertained herein was the development and characterization of a poly-(vinyl alcohol) (PVA) hydrogel cross-linked with glutaraldehyde and impregnated with 0.2% (w/w) nitrofurazone (NTZ), for topical applications. To verify the active principle release capability, one has determined (i) swelling profile, (ii) in vitro release of NTZ via UV-VIS spectrophotometry, and (iii) antimicrobial activity via exposure to the hydrogel of ATCC strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The optimized hydrogel was further characterized via scanning electron microscopy (SEM), infrared spectroscopy with Fourier transform, moisture content determinations and thermal analyses via thermal gravimetry (TGA). Swelling tests revealed a mass increase from 100+/-5% up to 350+/-11%. Incorporated NTZ displayed bactericidal activity, as expected, being released in a linearly controlled fashion above 6 ug/mL during experiment timeframes of 14 h. SEM analyses allowed verification of a homogeneous surface morphology, while infrared spectra showed that NTZ did not bind strongly to the cross-linked polymer. Furthermore, results from thermal analyses suggested a loss of thermal stability arising from incorporation of NTZ in the hydrogel. The optimized hydrogel exhibited characteristics with high potential for (antimicrobial) treatment of skin lesions. PMID- 25135343 TI - The current state of ethnic and racial disparities in cardiovascular care: lessons from the past and opportunities for the future. AB - Significant racial/ethnic disparities have been documented in cardiovascular care. Although health care quality is improving for many Americans, differences in clinical outcomes have persisted between racial/ethnic minority patients and non-minorities, even when income, education level, and site of care are taken into consideration. Potential causes of disparities are complex and are related to differences in risk factor prevalence and control, use of evidence-based procedures and medications, and social and environmental factors. Minority patients are more likely to receive care from lower-quality health care providers and institutions and experience more barriers to accessing care. Factors such as stereotyping and bias in medicine are hard to quantify, but likely contribute to differences in treatment. Recent trends suggest that some disparities are decreasing. Opportunities for change and improvement exist for patients, providers, and health care systems. Promising interventions, such as health policy changes, quality improvement programs, and culturally targeted community and clinic-based interventions offer hope that high-quality health care in the USA can be provided to all patients. PMID- 25135344 TI - Challenges and solutions to pre- and post-randomization subgroup analyses. AB - Subgroup analyses are commonly performed in the clinical trial setting with the purpose of illustrating that the treatment effect was consistent across different patient characteristics or identifying characteristics that should be targeted for treatment. There are statistical issues involved in performing subgroup analyses, however. These have been given considerable attention in the literature for analyses where subgroups are defined by a pre-randomization feature. Although subgroup analyses are often performed with subgroups defined by a post randomization feature--including analyses that estimate the treatment effect among compliers--discussion of these analyses has been neglected in the clinical literature. Such analyses pose a high risk of presenting biased descriptions of treatment effects. We summarize the challenges of doing all types of subgroup analyses described in the literature. In particular, we emphasize issues with post-randomization subgroup analyses. Finally, we provide guidelines on how to proceed across the spectrum of subgroup analyses. PMID- 25135345 TI - Advances in primary angiitis of the central nervous system. AB - Primary angiitis of the central nervous system (PACNS) is a rare idiopathic inflammatory syndrome targeting the vessels of the brain and spinal cord. Clinical presentation is variable, insidious, and non-specific; headache and encephalopathy are the most common symptoms. Multiple strokes affecting numerous vascular territories may be seen, and both focal and diffuse neurologic dysfunction may be present. Cerebrospinal fluid (CSF) analysis is crucial; a normal CSF along with normal brain parenchymal imaging carries a high negative predictive value in excluding PACNS. The role of imaging continues to evolve, and most patients have abnormal vascular imaging; however, the specificity of imaging for PACNS has historically been poor. Cerebral and meningeal biopsy is a valuable tool in confirming the diagnosis and excluding mimics. PACNS generally responds to immunosuppressive therapy. Failure to respond should prompt evaluation for an alternative diagnosis. Given the rarity of this disorder, exclusion of mimics such as the reversible cerebral vasoconstriction syndromes (RCVS) and infectious processes is essential. PMID- 25135346 TI - The role of cardiac rehabilitation following acute coronary syndromes. AB - Growing evidence highlights the important role of post-hospitalization care (i.e., secondary prevention) for patients with an acute coronary syndrome (ACS). While secondary prevention therapies are available that improve patient outcomes, receipt of those treatments by patients is suboptimal. Cardiac rehabilitation/secondary prevention (CR/SP) services are systematic, effective models of care that improve delivery of preventive therapies and patient outcomes after ACS, but unfortunately, patient participation in CR/SP has been suboptimal, due to patient-, provider-, and system-based barriers. Systematic processes, including automatic referral processes, help reduce these barriers and improve CR/SP participation, along with the associated health benefits. Strength of physician endorsement of CR/SP participation is another key step in improving CR/SP participation and patient outcomes following ACS. Accountability measures for CR/SP referral and enrollment, including performance measures and other quality of care methods, may help improve CR/SP delivery. Early evidence suggests that these measures have helped improve referral of eligible patients to CR/SP programs. PMID- 25135347 TI - Obstructive sleep apnea and acute coronary syndromes: etiology, risk, and management. AB - Obstructive sleep apnea (OSA) is characterized by upper airway collapse and airflow reduction despite respiratory effort, resulting in intermittent hypoxia and arousals, leading to a cascade of hemodynamic, autonomic, inflammatory, and metabolic effects, responsible for its adverse cardiovascular effect. OSA is an independent risk factor for cardiovascular disease, and its prevalence in patients presenting with acute coronary syndromes is up to 69%. Furthermore, OSA has been associated with increased risk of adverse events after an acute coronary syndrome. Continuous positive airway pressure is considered the mainstay of treatment of OSA and has been shown to reduce the risk of cardiovascular events. However, the proper time to start treatment in the acute setting is unknown. A prospective randomized clinical trial is currently underway to answer this question. PMID- 25135348 TI - Genetic variation at glucose and insulin trait loci and response to glucose insulin-potassium (GIK) therapy: the IMMEDIATE trial. AB - The mechanistic effects of intravenous glucose, insulin and potassium (GIK) in cardiac ischemia are not well understood. We conducted a genetic sub-study of the Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care (IMMEDIATE) Trial to explore effects of common and rare glucose and insulin-related genetic loci on initial to 6-h and 6- to 12-h change in plasma glucose and potassium. We identified 27 NOTCH2/ADAM30 and 8 C2CD4B variants conferring a 40-57% increase in glucose during the first 6 h of infusion (P<5.96 * 10(-6)). Significant associations were also found for ABCB11 and SLC30A8 single-nucleotide polymorphisms (SNPs) and glucose responses, and an SEC61A2 SNP with a potassium response to GIK. These studies identify genetic factors that may impact the metabolic response to GIK, which could influence treatment benefits in the setting of acute coronary syndromes (ACS). PMID- 25135351 TI - Effects of drying methods on the preparation of dexamethasone-loaded chitosan microspheres. AB - The purpose of this study was to investigate the effects of drying methods on the preparation of dexamethasone- (Dex-) loaded chitosan microspheres. Two drying methods, namely, air drying and freeze drying, were adopted. The physical properties of the beads were first investigated and then the loading and release of Dex were characterized. Finally, the bioactivity of released Dex was evaluated. The data showed that, compared with freeze-dried beads, air-dried beads were denser and smaller, and had lower swelling ratios, slower degradation rate and greater Rockwell hardness. In terms of drug delivery, air-dried beads had lower encapsulation efficiency and a slower release rate of Dex. Regarding bioactivity, both groups prompted cell differentiation without significant differences. However, Dex released from freeze-dried beads inhibited cell proliferation, while Dex released from air-dried beads did not. Based on these results, we conclude that incorporation of Dex enhanced the osteogenic potential of chitosan microspheres and drying methods did affect the physical properties of the chitosan microspheres, which further influenced the drug loading and release. At the moment, the air-drying method is more appropriate to prepare Dex-loaded chitosan microspheres. PMID- 25135349 TI - The synaptoneurosome transcriptome: a model for profiling the emolecular effects of alcohol. AB - Chronic alcohol consumption changes gene expression, likely causing persistent remodeling of synaptic structures via altered translation of mRNAs within synaptic compartments of the cell. We profiled the transcriptome from synaptoneurosomes (SNs) and paired total homogenates (THs) from mouse amygdala following chronic voluntary alcohol consumption. In SN, both the number of alcohol-responsive mRNAs and the magnitude of fold-change were greater than in THs, including many GABA-related mRNAs upregulated in SNs. Furthermore, SN gene co-expression analysis revealed a highly connected network, demonstrating coordinated patterns of gene expression and highlighting alcohol-responsive biological pathways, such as long-term potentiation, long-term depression, glutamate signaling, RNA processing and upregulation of alcohol-responsive genes within neuroimmune modules. Alterations in these pathways have also been observed in the amygdala of human alcoholics. SNs offer an ideal model for detecting intricate networks of coordinated synaptic gene expression and may provide a unique system for investigating therapeutic targets for the treatment of alcoholism. PMID- 25135352 TI - Field dependence-independence modulates the efficiency of filtering out irrelevant information in a visual working memory task. AB - Past research has demonstrated that field dependence-independence (FDI) can affect academic performance, selective attention, and working memory. However, the underlying mechanism of how FDI modulates selective attention and working memory is still unclear. Using event-related potential (ERP) techniques, specifically with the contralateral delay activity (CDA), the present study found that the correct response rates and CDA amplitudes in the 2-item and 2-item-2 distractor conditions were comparable for field independence (FI) participants. Field dependence (FD) participants performed worse, and the CDA amplitude was enhanced when distractors appeared. These results indicated that FI participants can filter out task-irrelevant information more efficiently than FD participants. The main difference between FD and FI individuals is their inhibition function. PMID- 25135353 TI - Frequency-dependent signal processing in apical dendrites of hippocampal CA1 pyramidal cells. AB - Depending on an animal's behavioral state, hippocampal CA1 pyramidal cells receive distinct patterns of excitatory and inhibitory synaptic inputs. The time dependent changes in the frequencies of these inputs and the nonuniform distribution of voltage-gated channels lead to dynamic fluctuations in membrane conductance. In this study, using a whole-cell patch-clamp method, we attempted to record and analyze the frequency dependencies of membrane responsiveness in Wistar rat hippocampal CA1 pyramidal cells following noise current injection directly into dendrites and somata under pharmacological blockade of all synaptic inputs. To estimate the frequency-dependent properties of membrane potential, membrane impedance was determined from the voltage response divided by the input current in the frequency domain. The cell membrane of most neurons showed low pass filtering properties in all regions. In particular, the properties were strongly expressed in the somata or proximal dendrites. Moreover, the data revealed nonuniform distribution of dendritic impedance, which was high in the intermediate segment of the apical dendritic shaft (~220-260MUm from the soma). The low-pass filtering properties in the apical dendrites were more enhanced by membrane depolarization than those in the somata. Coherence spectral analysis revealed high coherence between the input signal and the output voltage response in the theta-gamma frequency range, and large lags emerged in the distal dendrites in the gamma frequency range. Our results suggest that apical dendrites of hippocampal CA1 pyramidal cells integrate synaptic inputs according to the frequency components of the input signal along the dendritic segments receiving the inputs. PMID- 25135350 TI - Folic acid supplementation in pregnancy and implications in health and disease. AB - Maternal exposure to dietary factors during pregnancy can influence embryonic development and may modulate the phenotype of offspring through epigenetic programming. Folate is critical for nucleotide synthesis, and preconceptional intake of dietary folic acid (FA) is credited with reduced incidences of neural tube defects in infants. While fortification of grains with FA resulted in a positive public-health outcome, concern has been raised for the need for further investigation of unintended consequences and potential health hazards arising from excessive FA intakes, especially following reports that FA may exert epigenetic effects. The objective of this article is to discuss the role of FA in human health and to review the benefits, concerns and epigenetic effects of maternal FA on the basis of recent findings that are important to design future studies. PMID- 25135354 TI - Phosphorylation enhances recombinant HSP27 neuroprotection against focal cerebral ischemia in mice. AB - Heat shock protein 27 (HSP27) exerts cytoprotection against many cellular insults including cerebral ischemia. We previously indicated that intravenous injection of HSP27 purified from human lymphocytes (hHSP27) significantly reduced infarct volume following cerebral ischemia-reperfusion injury, while recombinant HSP27 (rHSP27) was less effective. Phosphorylation is important for HSP27 function, and hHSP27 was more highly phosphorylated than rHSP27. We hypothesized that MAPKAP kinase 2 in vitro-phosphorylated rHSP27 (prHSP27) might increase its brain protection. Mice underwent transient 1-h middle cerebral artery occlusion (MCAO), and then received tail-vein injections of one of the following 1h after reperfusion: hHSP27 as positive control, rHSP27, prHSP27, or bovine serum albumin (BSA) as control. We measured infarct volume, neurological deficits, neurological severity, physiological parameters, cell-death, oxidative stress, and inflammatory response. Compared with BSA controls (30.7+/-3.1mm(3), n=5), infarct volume was reduced by 67% in the hHSP27 positive-control group (10.1+/-4.6mm(3), P<0.001, n=5), 17% following rHSP27 (25.4+/-3.6mm(3), P<0.05, n=5), and 46% following prHSP27 (16.5+/-4.0mm(3), P<0.001, n=9). Compared to the rHSP27 and BSA treated groups, prHSP27 also reduced functional deficits, and significantly suppressed apoptosis, oxidative stress, and inflammatory responses. Here, we showed the superior neuroprotective effects of phosphorylated HSP27 by administering prHSP27. prHSP27 may be a useful therapeutic agent to protect against acute cerebral ischemic stroke. PMID- 25135355 TI - Down-regulation of PPARalpha in the spinal cord contributes to augmented peripheral inflammation and inflammatory hyperalgesia in diet-induced obese rats. AB - Obesity is associated with augmented peripheral inflammation and pain sensitivity in response to inflammatory stimulation, but the underlying mechanisms remain unclear. Emerging evidence has shown that activation of peroxisome proliferator activated receptor-alpha (PPARalpha) in the central nervous system controls peripheral inflammation and pain. We hypothesized that obesity might down regulate PPARalpha in the spinal cord, leading to enhanced peripheral inflammation and inflammatory hyperalgesia. Sprague-Dawley rats fed a high-fat diet (HF) for 12weeks developed metabolic disorder and displayed significantly decreased spinal PPARalpha expression and activity. Interestingly, intracerebroventricular (ICV) infusion of the PPARalpha activator palmitoylethanolamide (PEA) in HF-fed rats for 2weeks normalized spinal PPARalpha expression and activity without altering metabolic parameters. HF-fed rats were more sensitive to stimulation of the inflamed paw, and exhibited more severe paw edema following carrageenan injection, whereas HF-fed rats receiving ICV PEA had similar pain sensitivity and paw edema to LF-fed rats. No difference in the expression of inflammatory mediators or nuclear factor (NF)-kappaB activity was observed at baseline among groups. Carrageenan induced decreased PPARalpha expression and activity, increased spinal cord inflammatory mediator expression and NF-kappaB activity in both LF-and HF-fed rats. However, the increase was more pronounced in HF-fed rats and corrected by PEA. Intrathecal injection of small interfering RNA (siRNA) against PPARalpha in HF-fed rats completely abolished PEA effects on peripheral pain sensitivity and paw edema. These findings suggest that diet-induced obesity causes down-regulation of spinal PPARalpha, which facilitates the susceptibility to peripheral inflammatory challenge by increasing inflammatory response in the spinal cord, contributing to augmented peripheral inflammation and inflammatory hyperalgesia in obesity. PMID- 25135356 TI - Loudness modulation after transient and permanent hearing loss: implications for tinnitus and hyperacusis. AB - Loudness is the primary perceptual correlate of sound intensity. The relationship between sound intensity and loudness is not fixed, and can be modified by short term sound deprivation or stimulation. Deprivation increases sound sensitivity, whereas stimulation decreases it. We review the effects of short-term auditory deprivation and stimulation on the auditory central nervous system of humans and animals, and we extend the discussion to permanent auditory deprivation (hearing loss) and auditory pathologies of loudness perception. Although there is sufficient evidence to conclude that loudness can be modulated in normal hearing listeners by temporary sound deprivation and stimulation, evidence is scanter for the hearing-impaired listeners. In addition, cortical effects of sound deprivation and stimulation in humans, which may correlate with loudness coding, are still largely unknown and should be the target of future research. PMID- 25135357 TI - Mechanisms and targets of the modulatory action of S-nitrosoglutathione (GSNO) on inflammatory cytokines expression. AB - A number of experimental studies has documented that S-nitrosoglutathione (GSNO), the main endogenous low-molecular-weight S-nitrosothiol, can exert modulatory effects on inflammatory processes, thus supporting its potential employment in medicine for the treatment of important disease conditions. At molecular level, GSNO effects have been shown to modulate the activity of a series of transcription factors (notably NF-kappaB, AP-1, CREB and others) as well as other components of signal transduction chains (e.g. IKK-beta, caspase 1, calpain and others), resulting in the modulation of several cytokines and chemokines expression (TNFalpha, IL-1beta, IFN-gamma, IL-4, IL-8, RANTES, MCP-1 and others). Results reported to date are however not univocal, and a single main mechanism of action for the observed anti-inflammatory effects of GSNO has not been identified. Conflicting observations can be explained by differences among the various cell types studies as to the relative abundance of enzymes in charge of GSNO metabolism (GSNO reductase, gamma-glutamyltransferase, protein disulfide isomerase and others), as well as by variables associated with the individual experimental models employed. Altogether, anti-inflammatory properties of GSNO seem however to prevail, and exploration of the therapeutic potential of GSNO and analogues appears therefore warranted. PMID- 25135358 TI - Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic. AB - BACKGROUND: Autosomal recessive limb-girdle muscular dystrophies (LGMD2) include a number of disorders with heterogeneous etiology that cause predominantly weakness and wasting of the shoulder and pelvic girdle muscles. In this study, we determined the frequency of LGMD subtypes within a cohort of Czech LGMD2 patients using mutational analysis of the CAPN3, FKRP, SGCA, and ANO5 genes. METHODS: PCR sequencing analysis; sequence capture and targeted resequencing. RESULTS: Mutations of the CAPN3 gene are the most common cause of LGMD2, and mutations in this gene were identified in 71 patients in a set of 218 Czech probands with a suspicion of LGMD2. Totally, we detected 37 different mutations of which 12 have been described only in Czech LGMD2A patients. The mutation c.550delA is the most frequent among our LGMD2A probands and was detected in 47.1% of CAPN3 mutant alleles. The frequency of particular forms of LGMD2 was 32.6% for LGMD2A (71 probands), 4.1% for LGMD2I (9 probands), 2.8% for LGMD2D (6 probands), and 1.4% for LGMD2L (3 probands).Further, we present the first results of a new approach established in the Czech Republic for diagnosis of neuromuscular diseases: sequence capture and targeted resequencing. Using this approach, we identified patients with mutations in the DYSF and SGCB genes. CONCLUSIONS: We characterised a cohort of Czech LGMD2 patients on the basis of mutation analysis of genes associated with the most common forms of LGMD2 in the European population and subsequently compared the occurrence of particular forms of LGMD2 among countries on the basis of our results and published studies. PMID- 25135359 TI - Ethnomedicinal and phytochemical review of Pakistani medicinal plants used as antibacterial agents against Escherichia coli. AB - Medicinal plants have always been part of human culture and have the potential to cure different diseases caused by microorganisms. In Pakistan, biologists are mainly focusing on plants' antimicrobial activities against Escherichia coli due to its increasing resistance to antibiotics. In total, extracts from 34 ethnomedicinally valuable Pakistani plants were reported for in-vitro anti-E. coli activities. Mostly methanolic extracts of medicinal plants were used in different studies, which have shown comparatively higher inhibitory activities against E. coli than n-hexane and aqueous extracts. It has been found that increasing concentration (mg/ml) of methanolic extract can significantly increase (p<0.01) anti-E. coli activities. Not all medicinal plants are extracted in solvents others than above, which should also be tested against E. coli. Moreover, medicinal plant species must be fully explored phytochemically, which may lead to the development of new drugs. PMID- 25135361 TI - Interaction of Leukocyte Elastase Inhibitor/L-DNase II with BCL-2 and BAX. AB - Leukocyte Elastase Inhibitor (LEI, also called serpin B1) is a protein involved in apoptosis among other physiological processes. We have previously shown that upon cleavage by its cognate protease, LEI is transformed into L-DNase II, a protein with a pro-apoptotic activity. The caspase independent apoptotic pathway, in which L-DNase II is the final effector, interacts with other pro-apoptotic molecules like Poly-ADP-Ribose polymerase (PARP) or Apoptosis Inducing Factor (AIF). The screening of LEI/L-DNase II interactions showed a possible interaction with several members of the BCL-2 family of proteins which are known to have a central role in the regulation of caspase dependent cell death. In this study, we investigated the regulation of LEI/L-DNase II pathway by two members of this family of proteins: BAX and BCL-2, which have opposite effects on cell survival. We show that, in both BHK and HeLa cells, LEI/L-DNase II can interact with BCL-2 and BAX in apoptotic and non-apoptotic conditions. These proteins which are usually thought to be anti-apoptotic and pro-apoptotic respectively, both inhibit the L-DNase II pro-apoptotic activity. These results give further insight in the regulation of caspase independent pathways and highlight the involvement of the intracellular environment of a given protein in the determinism of its function. They also add a link between caspase-dependent and independent pathways of apoptosis. PMID- 25135362 TI - Ubiquitin proteasome system-mediated degradation of synaptic proteins: An update from the postsynaptic side. AB - The ubiquitin proteasome system is one of the principle mechanisms for the regulation of protein homeostasis in mammalian cells. In dynamic cellular structures such as neuronal synapses, ubiquitin proteasome system and protein translation provide an efficient way for cells to respond promptly to local stimulation and regulate neuroplasticity. The majority of research related to long-term plasticity has been focused on the postsynapses and has shown that ubiquitination and subsequent degradation of specific proteins are involved in various activity-dependent plasticity events. This review summarizes recent achievements in understanding ubiquitination of postsynaptic proteins and its impact on synapse plasticity and discusses the direction for advancing future research in the field. PMID- 25135360 TI - "Fast track" rehabilitation after gastric cancer resection: experience with 80 consecutive cases. AB - BACKGROUND: To evaluate the safety, efficacy and outcomes of fast-track rehabilitation applied to gastric cancer proximal, distal and total gastrectomy. METHODS: Eighty consecutive patients undergoing gastric cancer resection performed by a single surgeon, received perioperative multimodal rehabilitation. Demographic and operative data, gastrointestinal function, postoperative hospital stays, surgical and general complications and mortality were assessed prospectively. RESULTS: Of the 80 patients (mean age 56.3 years), 10 (12.5%) received proximal subtotal gastrectomy (Billroth I), 38 (47.5%) received distal (Billroth II), and 32 (40%) received total gastrectomy (Roux-en-Y). Mean operative time was 104.9 minutes and intraoperative blood loss was 281.9 ml. Time to first flatus was 2.8 +/- 0.5 postoperative days. Patients were discharged at a mean of 5.3 +/- 2.2 postoperative days; 30-day readmission rate was 3.8%. In hospital mortality was 0%; general and surgical complications were both 5%. CONCLUSIONS: Fast-track multimodal rehabilitation is feasible and safe in patients undergoing gastric cancer resection and may reduce time to first flatus and postoperative hospital stays. PMID- 25135363 TI - Aerobic granular sludge mediated biodegradation of an organophosphorous ester, dibutyl phosphite. AB - Dibutyl phosphite, an organophosphorous compound, finds applications in different chemical industries and processes. Here, we report an efficient approach of biodegradation to be eventually used in bioremediation of dibutyl phosphite. Aerobic granules capable of dibutyl phosphite biodegradation were cultivated in a sequencing batch reactor (SBR). The SBR was operated with a 24-h cycle by feeding with dibutyl phosphite as a cosubstrate along with acetate. During the course of the SBR operation, aerobic granules of 0.9 +/- 0.3 mm size were developed. Complete biodegradation of 1.4, 2 and 3 mM of dibutyl phosphite was achieved in 4, 5 and 8 h, respectively, accompanied by stoichiometric release of phosphite (H3 PO3). Phosphatase activity in the dibutyl phosphite-degrading granular biomass was 3- and 1.5-fold higher as compared to the activated sludge (seed biomass) and acetate-fed aerobic granules, respectively, indicating involvement in the hydrolysis of dibutyl phosphite. Microbial community analysis by t-RFLP showed the presence of 12 different bacterial types. Two bacterial strains capable of growth on dibutyl phosphite as sole carbon source were isolated and characterized as Acidovorax sp. and Sphingobium sp. The results show that aerobic microbial granules based process is suitable for the treatment of dibutyl phosphite contaminated water. PMID- 25135364 TI - Left ventricular remodeling after acute myocardial infarction: the influence of viability and revascularization - an echocardiographic substudy of the VIAMI trial. AB - BACKGROUND: Viability seems to be important in preventing ventricular remodeling after acute myocardial infarction (AMI). We investigated the influence of viability, as demonstrated with low-dose dobutamine echocardiography, and the role of early revascularization on the process of left ventricular (LV) remodeling after AMI. METHODS: We retrospectively investigated 224 patients who were initially included in the viability-guided angioplasty after acute myocardial infarction-trial (VIAMI-trial). Patients in the VIAMI-trial did not undergo a primary or rescue percutaneous coronary intervention and were stable in the early in-hospital phase. Patients underwent viability testing within 72 hours after AMI. Patients with viability were randomized to an invasive strategy or an ischemia-guided strategy. Follow-up echocardiography was performed at a mean of 205 days. In this echocardiographic substudy, patients were divided into three new groups: group 1, viable and revascularized before follow-up echocardiogram; group 2, viable, but medically treated; and group 3, non-viable patients. RESULTS: Group 1 showed preservation of LV volume indices. The ejection fraction (EF) increased significantly from 54.0% to 57.5% (P = 0.047). Group 2 showed a significant increase in LV volume indices with no improvement in EF (53.3% versus 53.0%, P = 0.86). Group 3 showed a significant increase in LV volume indices, with a decrease in EF from 53.5% to 49.1% (P = 0.043). Multivariate logistic regression analysis indicated the number of viable segments and revascularization during follow-up as independent predictors for EF improvement, especially in patients with lower EF at baseline. CONCLUSION: Viability early after AMI is associated with improvement in LV function after revascularization. When viable myocardium is not revascularized, the LV tends to remodel with increased LV volumes, without improvement of EF. Absence of viability results in ventricular dilatation and deterioration of EF, irrespective of revascularization status. TRIAL REGISTRATION: NCT00149591 (assigned: 6 September 2005). PMID- 25135365 TI - Topics of internal medicine for undergraduate dental education: a qualitative study. AB - INTRODUCTION: Due to the ageing population, internal medicine has become increasingly important for dental education. Although several studies have reported dentists' dissatisfaction with their internal medicine training, no guidelines exist for internal medicine learning objectives in dental education. The aim of this study was to identify topics of internal medicine considered to be relevant for dental education by dentists and internists. METHODS: Eight dentists from private dental practices in Hamburg and eight experienced internal medicine consultants from Hamburg University Hospital were recruited for semi structured interviews about internal medicine topics relevant for dentists. Internal diseases were clustered into representative subspecialties. Dentists and internists were also asked to rate medical diseases or emergencies compiled from the literature by their relevance to dental education. RESULTS: Coagulopathy and endocarditis were rated highest by dentists, whilst anaphylaxis was rated highest by internists. Dentists rated hepatitis, HIV, organ transplantation and head/neck neoplasm significantly higher than internists. The largest number of different internal diseases mentioned by dentists or internists could be clustered under cardiovascular diseases. The number of specific diseases dentists considered to be relevant for dental education was higher in the subspecialties cardiovascular diseases, haematology/oncology and infectiology. CONCLUSION: We identified the internal medicine topics most relevant for dental education by surveying practising dentists and internists. The relevance of these topics should be confirmed by larger quantitative studies to develop guidelines how to design specific learning objectives for internal medicine in the dental curriculum. PMID- 25135366 TI - Gastrointestinal cancer: FOLFIRI plus cetuximab--preferred first-line treatment for mCRC. PMID- 25135368 TI - Breast cancer: Subclones-go forth and mutate. PMID- 25135369 TI - Breast cancer: PALB2--a new player in hereditary breast cancer. PMID- 25135367 TI - Precision therapy for lymphoma--current state and future directions. AB - Modern advances in genomics and cancer biology have produced an unprecedented body of knowledge regarding the molecular pathogenesis of lymphoma. The diverse histological subtypes of lymphoma are molecularly heterogeneous, and most likely arise from distinct oncogenic mechanisms. In parallel to these advances in lymphoma biology, several new classes of molecularly targeted agents have been developed with varying degrees of efficacy across the different types of lymphoma. In general, the development of new drugs for treating lymphoma has been mostly empiric, with a limited knowledge of the molecular target, its involvement in the disease, and the effect of the drug on the target. Thus, the variability observed in clinical responses likely results from underlying molecular heterogeneity. In the era of personalized medicine, the challenge for the treatment of patients with lymphoma will involve correctly matching a molecularly targeted therapy to the unique genetic and molecular composition of each individual lymphoma. In this Review, we discuss current and emerging biomarkers that can guide treatment decisions for patients with lymphoma, and explore the potential challenges and strategies for making biomarker-driven personalized medicine a reality in the cure and management of this disease. PMID- 25135371 TI - Impact of osteoid osteomas of the hip on the size and fatty infiltration of the thigh muscles. AB - We aimed to assess the impact of osteoid osteomas of the hip on the size and fatty infiltration of the muscle thigh in 42 patients. The thigh circumference, cross-sectional areas, and fatty atrophy of four anterior muscles were assessed on magnetic resonance axial T1-weighted images. A significant fatty atrophy was found in the studied muscles of the ipsilateral thigh except for the rectus femoris. No significant association was demonstrated with pain duration suggesting that muscle atrophy may rather be related to the locoregional inflammation than subsequent to the disuse of the limb. PMID- 25135370 TI - An economic evaluation of maxillary implant overdentures based on six vs. four implants. AB - BACKGROUND: The purpose of the present study was to assess the value for money achieved by bar-retained implant overdentures based on six implants compared with four implants as treatment alternatives for the edentulous maxilla. METHODS: A Markov decision tree model was constructed and populated with parameter estimates for implant and denture failure as well as patient-centred health outcomes as available from recent literature. The decision scenario was modelled within a ten year time horizon and relied on cost reimbursement regulations of the German health care system. The cost-effectiveness threshold was identified above which the six-implant solution is preferable over the four-implant solution. Uncertainties regarding input parameters were incorporated via one-way and probabilistic sensitivity analysis based on Monte-Carlo simulation. RESULTS: Within a base case scenario of average treatment complexity, the cost effectiveness threshold was identified to be 17,564 ? per year of denture satisfaction gained above of which the alternative with six implants is preferable over treatment including four implants. Sensitivity analysis yielded that, depending on the specification of model input parameters such as patients' denture satisfaction, the respective cost-effectiveness threshold varies substantially. CONCLUSIONS: The results of the present study suggest that bar retained maxillary overdentures based on six implants provide better patient satisfaction than bar-retained overdentures based on four implants but are considerably more expensive. Final judgements about value for money require more comprehensive clinical evidence including patient-centred health outcomes. PMID- 25135372 TI - Pregnancy outcomes of mothers with an alcohol-related diagnosis: a population based cohort study for the period 1983-2007. AB - OBJECTIVE: To examine fetal outcomes of mothers with an alcohol-related diagnosis. DESIGN: Population-based cohort. SETTING: Western Australia (WA). POPULATION: Births on the WA Midwives Notification System (1983-2007). METHODS: Infants of mothers with an alcohol-related diagnosis [International Classification of Disease (ICD), 9th/10th revisions] recorded on WA health data sets (non-Aboriginal n = 13 807; Aboriginal n = 9766) were identified through the WA data linkage system. A comparison cohort of infants born to mothers without an alcohol diagnosis was frequency matched on maternal age, year of birth of the offspring, and Aboriginal status (non-Aboriginal n = 40 148; Aboriginal n = 20 643). MAIN OUTCOME MEASURES: Poisson regression-generated adjusted relative risk (aRR) and 95% confidence intervals (95% CIs) for small for gestational age (SGA), preterm birth, and low-Apgar score, calculated separately for non-Aboriginal and Aboriginal infants of mothers with an alcohol diagnosis recorded during pregnancy and any alcohol diagnosis. Population-attributable fractions were calculated. RESULTS: The aRR for non-Aboriginal infants when a maternal alcohol diagnosis was recorded during pregnancy ranged from 1.79 (95% CI 1.42-2.16) for SGA to 2.57 (95% CI 1.69-4.27) for preterm birth <32 weeks of gestation, and for Aboriginal infants ranged from 2.69 (95% CI 2.28-3.16) to 1.99 (95% CI 1.40-2.84), respectively. The highest population-attributable fractions were for any alcohol diagnosis and for Aboriginal infants. For Aboriginal births, approximately 9% (95% CI 4.74-12.97) and 10.1% (95% CI 5.50-14.49) of moderate and very preterm births, respectively, and 24.4% (95% CI 13.5-21.2%) of SGAs were attributable to having a mother with any alcohol-related diagnosis. CONCLUSIONS: Mothers with an alcohol diagnosis are at increased risk of poor pregnancy outcomes. The public health impact of maternal alcohol-use disorders on fetal outcomes is significant. PMID- 25135374 TI - [Hyperostosis of the internal auditory canal : An incidental finding?]. AB - In contrast to the fairly common exostoses in the external auditory canal, hyperostoses and osteomas of the internal auditory canal are extremely rare. In this case report we present a patient with sudden right-sided sensorineural hearing loss, in whom imaging revealed hyperostosis with bilateral stenosis of the internal auditory canal. Whether the connection of such radiological findings with dysfunction of cranial nerves VII and VIII be causal or coincidental is controversially discussed in the literature. Therefore, the indication for surgical intervention should be considered with extreme caution. Despite examination of our radiology database comprising almost 1000 MRI/CT temporal bone investigations, we could find no other cases of hyperostosis of the petrous bone. This case thus represents a rare disease, which should be considered a differential diagnosis. PMID- 25135373 TI - [How reliable are non-instrumental assessment tools for dysphagia?]. AB - BACKGROUND: The requirement for otorhinolaryngologists and phoniatricians to diagnose dysphagia and evaluate its extent is on the rise, particularly in light of demographic changes. The gold standards in confirmatory diagnostics are fiberoptic endoscopic evaluation of swallowing (FEES) and the videofluoroscopic swallowing examination (VFS). Standardized assessments, such as questionnaires or assessments involving probatory swallows are often applied as screening or supportive measures. This article aims to give a critical overview of the assessment tools frequently used in clinical routine. Test quality is assessed, particularly compared to FEES and VFS. METHODS: A selective literature search using PubMed has been conducted. RESULTS: On the basis of this lierature search, 48 assessment tools were identified. These can be classified into screening tools, instrument-based tools (implementation standards and evaluation protocols) and questionnaire-based assessment inventories. DISCUSSION: In order to diagnose and evaluate dysphagia on the basis of assessment critieria, clinicians should be aware of indications for, as well as the advantages, disadvantages and test quality of the assessment tools. Considering the different assessment tools for anamnesis and probatory swallowing, rather low sensitivities and specificities for possible penetration and aspiration are evident. In cases where these symptoms of dysphagia are not evident and reliably assessable, confirmatory assessment via FEES or VFS is essential. PMID- 25135375 TI - [Olfactory function in old age]. AB - Olfactory function decreases with age. This is frequent: one in four individuals above 52 years of age exhibits olfactory loss. This decrease in olfactory function can be seen at all levels of olfactory information processing, both on a functional and a morphological level. Recent studies, however, indicate that olfactory loss with age may not be an inevitable fate. PMID- 25135376 TI - Associations among late chronotype, body mass index and dietary behaviors in young adolescents. AB - BACKGROUND/OBJECTIVES: Levels of pediatric obesity continue to rise. Previous evidence has linked short sleep duration and/or poor sleep quality to obesity development, although objective data are limited. As adolescents transition through puberty, circadian shifts occur, resulting in sleep loss. However, little is known whether chronotype is associated with body mass index (BMI) or dietary behaviors in adolescents. We hypothesized late chronotype would be positively associated with BMI and poorer dietary behaviors. SUBJECTS/METHODS: A total of 511 UK young adolescents (11-13 years) from eight secondary schools across the Midlands region (UK) participated in the Midlands Adolescent Schools Sleep Education Study (MASSES), a cross-sectional study to assess potential relationships between chronotype and BMI z-score as well as dietary habits. Height (cm) and weight (kg) were objectively measured for BMI calculation and participants completed a questionnaire to assess dietary habits. A subsample of 236 adolescents wore wrist actigraphy for 7 days to estimate average sleep duration (weekday, weekend and combined) and sleep efficiency. RESULTS: Definitely evening chronotype was positively associated with BMI z-score compared to definitely morning chronotypes beta = 0.51, P < 0.01, after adjustment. Higher frequency of consuming unhealthy snacks, night-time caffeine consumption and inadequate daily intake of fruit/vegetables were also associated with later chronotype (all P ? 0.01). Actigraphy estimated sleep duration was an independent predictor of BMI z-score beta = -0.36, P < 0.001. Sleep efficiency did not predict BMI z-score after adjustment, beta = -0.03, P = 0.07. CONCLUSIONS: Later chronotype young adolescents are at risk of increased BMI and poorer dietary behaviors. Although short sleep duration, but not sleep efficiency, was also an independent risk factor for increased BMI, different mechanisms may be driving the late chronotype and shorter sleep duration associations with BMI in this age group. Sleep hygiene education may help adolescents to better understand the impact of sleeping habits on physical health. PMID- 25135377 TI - Does the FTO gene interact with the socioeconomic status on the obesity development among young European children? Results from the IDEFICS study. AB - BACKGROUND: Various twin studies revealed that the influence of genetic factors on psychological diseases or behaviour is more expressed in socioeconomically advantaged environments. Other studies predominantly show an inverse association between socioeconomic status (SES) and childhood obesity in Western developed countries. The aim of this study is to investigate whether the fat mass and obesity-associated (FTO) gene interacts with the SES on childhood obesity in a subsample (N = 4406) of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) cohort. METHODS: A structural equation model (SEM) is applied with the latent constructs obesity, dietary intakes, physical activity and fitness habits, and parental SES to estimate the main effects of the latter three variables and a FTO polymorphism on childhood obesity. Further, a multiple group SEM is used to explore whether an interaction effect exists between the single nucleotide polymorphism rs9939609 within the FTO gene and SES. RESULTS: Significant main effects are shown for physical activity and fitness (standardised [betacrc ](s) = -0.113), SES ([betacrc ](s) = -0.057) and the FTO homozygous AA risk genotype ([betacrc ](s) = -0.177). The explained variance of obesity is ~9%. According to the multiple group approach of SEM, we see an interaction between SES and FTO with respect to their effect on childhood obesity (Deltachi(2) = 7.3, df = 2, P = 0.03). CONCLUSION: Children carrying the protective FTO genotype TT seem to be more protected by a favourable social environment regarding the development of obesity than children carrying the AT or AA genotype. PMID- 25135378 TI - Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie University Hospital: concentration of C3 p.I1157T mutation. AB - Atypical hemolytic uremic syndrome (aHUS) is caused by abnormalities of the complement system and has a significantly poor prognosis. The clinical phenotypes of 12 patients in nine families with aHUS with familial or recurrent onset and ADAMTS13 activity of >=20 % treated at the Mie University Hospital were examined. In seven of the patients, the first episode of aHUS occurred during childhood and ten patients experienced a relapse. All patients had renal dysfunction and three had been treated with hemodialysis. Seven patients experienced probable triggering events including common cold, influenza, bacterial infection and/or vaccination for influenza. All patients had entered remission, and renal function was improved in 11 patients. DNA sequencing of six candidate genes, identified a C3 p.I1157T missense mutation in all eight patients in six families examined and this mutation was causative for aHUS. A causative mutation THBD p.D486Y was also identified in an aHUS patient. Four missense mutations, CFH p.V837I, p.Y1058H, p.V1060L and THBD p.R403K may predispose to aHUS manifestation; the remaining seven missense mutations were likely neutral. In conclusion, the clinical phenotypes of aHUS are various, and there are often trigger factors. The C3 p.I1157T mutation was identified as the causative mutation for aHUS in all patients examined, and may be geographically concentrated in or around the Mie prefecture in central Japan. PMID- 25135379 TI - University Gynaecology and Obstetrics, quo vadis? A Department of Women's Health University Women's Hospital of the future? AB - PURPOSE: Numerous changes in society, science and health care challenge gynaecology and obstetrics. These challenges include the maintenance of excellence in research, commercial potential and clinical innovation, as well as the maintenance of adequate human resources, new standards for patient orientation and individualised medicine. METHODS: Based on a SWOT analysis of the status quo, of local and national quality data, a search regarding national conceptions and of international best practice for women's health centres, the model of a Department of Women's Health was developed. RESULTS: The Department, consisting of a University Hospital and a Research Institute, should interlink clinical care and science. With the establishment of the department, a pool of expertise is achieved which encompasses gynaecology and obstetrics from basic care to the high-technology segments, as well as all the scientific areas relevant to the medical discipline and women's health, including health services research. Preservation and attraction of personnel resources are based on the department's excellence, on reliable perspectives and the flexibility of job profiles, which also result from the close connection between care and research and the expansion of perspectives on women's health. CONCLUSIONS: Methodological diversity and inter-professionalism build the appropriate base for the further development of research fields. At the same time, the Department creates space for the consolidation of the core areas and the integration of sub-disciplines (clinical and scientific) to maintain the unity of this discipline. Via the scientific monitoring of the implementation, suitable elements can be highlighted for transfer to other facilities. PMID- 25135380 TI - Relationship between first trimester visualization of the intracranial translucency and spina bifida. AB - PURPOSE: To establish a reference range for the intracranial translucency (IT). METHODS: In this prospective study, we examined 596 singleton fetuses at 11-14 weeks of gestation using transabdominal ultrasonography. The distribution curves of the anterior-posterior diameter of the IT were established according to the gestational weeks, and the percentiles for 11-14 weeks of gestation were calculated. Regression analysis was performed to estimate the relationship between the anterior-posterior diameter of the IT and other fetal biometric parameters. RESULTS: The mean anterior-posterior diameter of the IT was 1.8 +/- 0.4 mm. From 11 to 14 weeks of gestation, the IT diameter increased linearly with advancing gestation. The linear regression equation for the IT * crown-rump length (CRL) was IT = CRL * 0.0184 + 0.575 (R = 0.385, p < 0.001). The linear regression equation for the IT * biparietal diameter (BPD) was IT = BPD * 0.0532 + 0.632 (R = 0.346, p < 0.001). The linear regression equation for IT * gestational age (days) (GA) was ICT = GA * 0.024 - 0.339 (R = 0.25, p < 0.001). The linear regression analysis revealed significant correlations of the IT with CRL, BPD, and GA. CONCLUSION: The IT increases linearly with increasing CRL, BPD, gestational age in weeks, and gestational age in days. PMID- 25135381 TI - Modest cooling therapies (35oC to 37.5oC) for traumatic brain injury. AB - BACKGROUND: Animal models of traumatic brain injury suggest that induced normothermia (36.5 or 37 oC), compared to induced hyperthermia (39 oC), improves histopathological and neurobehavioural outcomes. Observational clinical studies of patients with TBI suggest an association between raised body temperature and unfavourable outcome, although this relationship is inconsistent. OBJECTIVES: To assess the effects of modest cooling therapies (defined as any drug or physical therapy aimed at maintaining body temperature between 35 oC and 37.5 oC) when applied to patients in the first week after traumatic brain injury. SEARCH METHODS: The most recent search was run on 23(rd) September 2013. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), ISI WOS: SCI-EXPANDED (1970) & CPCI-S (1990), PubMed and trials registries together with reference checking. SELECTION CRITERIA: All completed randomised, controlled and placebo-controlled trials published or unpublished, where modest cooling therapies were applied in the first week after traumatic brain injury. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to relevant trials. MAIN RESULTS: We were unable to find any randomised controlled trials of modest cooling therapies after traumatic brain injury. AUTHORS' CONCLUSIONS: In order to further explore the preliminary findings provided by animal models and observational clinical studies that suggests there may be a beneficial effect of modest cooling for TBI, randomised trials designed to explore the effect of these interventions on patient-centred outcomes are needed. PMID- 25135382 TI - Minimum 1-year results of mesh spiral-sling procedure in managing refractory and primary disabling stress urinary incontinence. AB - INTRODUCTION AND HYPOTHESIS: We present our minimum 1-year results with a mesh spiral-sling procedure (MSSP) for managing refractory and disabling stress urinary incontinence (SUI) in women. METHODS: Thirty-four women were treated with MSSP between 2007 and 2011. Six had incomplete data and were excluded from analysis. Study cohort comprised 21 women with refractory (mean number of previous surgeries 2.2; range 1-6) and seen with primary disabling SUI. All patients had marked intrinsic sphincter deficiency (ISD) with a Valsalva leak point pressure (VLPP) <60 cm H2O. Preoperative workup included assessing the impact of voiding symptoms using the International Consultation on Incontinence Questionnaire--Short Form (ICIQ-SF), estimating the daily number of pads, and urodynamic studies. Preoperative and postoperative findings were compared using the Wilcoxon signed-rank test. RESULTS: Intraoperative unilateral bladder-neck perforation occurred in two women during dorsal urethrolysis. With a mean follow up of 26 months (range 12-48), SUI was cured in 71.4% of patients. Distal urethral reconstruction with vaginal mucosal flaps was performed in two patients with short urethral length (<2.5 cm) due to recurrence of SUI 10 months after MSSP. Mean ICIQ-SF score decreased from 19.4 +/- 3.6 preoperatively to 7.3 +/- 2.8 postoperatively (p = 0.001). Mean daily pad number decreased from 5.2 preoperatively to 1.2 postoperatively (p = 0.02). Urethral or vaginal erosion was not observed in any case during follow-up. CONCLUSION: Using spiral slings may be a viable option in managing refractory and disabling SUI. PMID- 25135383 TI - Effect of high-intensity training versus moderate training on peak oxygen uptake and chronotropic response in heart transplant recipients: a randomized crossover trial. AB - In heart transplant (HTx) recipients, there has been reluctance to recommend high intensity interval training (HIIT) due to denervation and chronotropic impairment of the heart. We compared the effects of 12 weeks' HIIT versus continued moderate exercise (CON) on exercise capacity and chronotropic response in stable HTx recipients >12 months after transplantation in a randomized crossover trial. The study was completed by 16 HTx recipients (mean age 52 years, 75% males). Baseline peak oxygen uptake (VO2peak ) was 22.9 mL/kg/min. HIIT increased VO2peak by 4.9 +/- 2.7 mL/min/kg (17%) and CON by 2.6 +/- 2.2 mL/kg/min (10%) (significantly higher in HIIT; p < 0.001). During HIIT, systolic blood pressure decreased significantly (p = 0.037) with no significant change in CON (p = 0.241; between group difference p = 0.027). Peak heart rate (HRpeak ) increased significantly by 4.3 beats per minute (p = 0.014) after HIIT with no significant change in CON (p = 0.34; between group difference p = 0.027). Heart rate recovery (HRrecovery ) improved in both groups with a trend toward greater improvement after HIIT. The 5 month washout showed a significant loss of improvement. HIIT was well tolerated, had a superior effect on oxygen uptake, and led to an unexpected increase in HRpeak accompanied by a faster HRrecovery . This indicates that the benefits of HIIT are partly a result of improved chronotropic response. PMID- 25135385 TI - Driving Ability in Patients with Severe Chronic Low Back or Osteoarthritis Knee Pain on Stable Treatment with Tapentadol Prolonged Release: A Multicenter, Open label, Phase 3b Trial. AB - INTRODUCTION: Strong centrally acting analgesics, including tapentadol prolonged release (PR), have demonstrated efficacy for the management of non-malignant, chronic pain. Maintaining patient independence, including the ability to drive safely, is a key goal of long-term analgesic therapy. This multicenter, open label, phase 3b trial evaluated the effects of tapentadol PR on driving ability. METHODS: This study included patients who had completed previous tapentadol PR trials for severe low back or osteoarthritis pain. After at least 6 weeks of dose stability, patients continued taking tapentadol PR (50-250 mg twice daily) and could take supplemental immediate-release tapentadol 50 mg, except on the day before or day of the driving test (before the test). Pain intensity was assessed using an 11-point numerical rating scale. The Vienna Test System-Traffic Plus was used to assess cognitive and psychomotor function. The key surrogate parameter for driving ability was a global judgment based on 6 battery tests. RESULTS: Thirty-eight patients enrolled and completed the trial, and 35 patients completed all 6 tests. Pain scores remained unchanged from enrollment to final visit [mean (standard deviation) change, -0.2 (1.0)]. Approximately two-thirds [65.7% (23/35)] of patients were classified as fit to drive based on the global judgment of driving-specific ability [34.3% (12/35) not fit to drive]. Total daily tapentadol PR dose (>200 vs. <=200 mg/day) did not affect global judgment of driving ability (P = 0.4885). Two adverse events (considered unrelated to study drug) were reported. CONCLUSION: Results suggest that most patients receiving a stable dose of tapentadol PR for severe, chronic pain would be able to drive, consistent with earlier studies evaluating stable treatment with strong opioids. Study design limitations and needs for individual patient assessment must be considered in clinical practice. PMID- 25135384 TI - Oxycodone/Naloxone: role in chronic pain management, opioid-induced constipation, and abuse deterrence. AB - The use of opioids in the treatment of chronic pain is widespread; the prevalence of specific opioids varies from country to country and depends on product availability, national formulary systems, and provider preferences. Patients often receive opioids for legitimate treatment of pain conditions, but on the opposite side of the spectrum, nonmedical use of opioids is a significant public health concern. Opioids are associated with several side effects, and constipation is the most commonly reported and persistent symptom. Unlike some adverse effects associated with opioid use, tolerance does not develop to constipation. Opioid-induced constipation (OIC) is the most prevalent patient complaint associated with opioid use and has been associated with declines in various quality of life measures. OIC can be extremely difficult for patients to tolerate and may prompt patients to decrease or discontinue opioid treatment. Current management strategies for OIC are often insufficient. A prolonged-release formulation of oxycodone/naloxone (OXN) has been investigated for the treatment of nonmalignant and cancer pain and mitigation of OIC, and evidence is largely favorable. Studies have demonstrated the capability of OXN to alleviate OIC while maintaining pain control comparable to oxycodone-only regimens. There is insufficient evidence for OXN efficacy for patients with mild OIC or patients maintained on high doses of opioids, and use in these populations is controversial. The reduction of costs associated with OIC may provide overall cost effectiveness with OXN. Additionally, the presence of naloxone may deter abuse/misuse by those seeking to misuse the formulation by modes of administration other than oral ingestion. Most studies to date have occurred in European countries, and phase 3 trials continue in the United States. This review will include current therapeutic options for pain and constipation, unique characteristics of OXN, evidence related to use of OXN and its place in therapy, discussion of opioid abuse/misuse, and various abuse-deterrent mechanisms, and areas of continuing research. PMID- 25135386 TI - A Model-Based Meta-analysis to Compare Efficacy and Tolerability of Tramadol and Tapentadol for the Treatment of Chronic Non-Malignant Pain. AB - INTRODUCTION: Pain is a major symptom in many medical conditions which can be relieved thanks to analgesics. The goal of this work was to present an indirect comparison of efficacy and tolerability profiles of two analgesics, tramadol and tapentadol, in patients with chronic non-malignant pain. METHODS: In the absence of a head-to-head comparison between these two opioid drugs, model-based meta analyses were used to characterize the pain intensity time dynamics and evaluate the proportions of most frequent adverse events (constipation, nausea, vomiting, dizziness, and somnolence) and drop-outs (due to adverse event, as well as due to lack of efficacy) in each treatment group. Using these models, the investigational treatments were compared on the basis of Monte Carlo simulation outcomes. RESULTS: Data were extracted from 45 Phase II and Phase III studies representing a total of 81 treatment arms, i.e., approximately 13,000 patients. The pain intensity model shows, that after having adjusted for differences in baseline pain intensity and placebo effects, tramadol 300 mg once daily (qd) was slightly more effective in reducing pain than tapentadol 100-250 mg twice daily (bid), with a 46% change from baseline for the former versus 36% for the latter. From a tolerability standpoint, both drugs showed, as expected, increased risks of adverse events compared to placebo. Yet, tapentadol was associated with slightly lower risks of constipation, and nausea than tramadol. CONCLUSION: Overall, the analysis showed that the benefit-risk profiles of tramadol 300 mg qd and tapentadol 100-250 mg bid were approximately even. The amount of data to characterize dose-response relationships was sufficient only in the tramadol group; public access to tapentadol efficacy and tolerability readouts across a wide dose range in chronic non-malignant pain would allow a comparison of therapeutic indices, a straight quantitation of the benefit-risk ratio. Knowing that their side-effects have been identified as potential hindrance to prescription, a broad and open access to clinical trial data in this indication is encouraged in order to facilitate the evaluation of the opiate analgesics clinical utility. PMID- 25135387 TI - Systemic ropivacaine diminishes pain sensitization processes: a randomized, double-blinded, placebo-controlled, crossover study in healthy volunteers. AB - INTRODUCTION: Ropivacaine is a local anesthetic widely used for regional anesthesia. One of its advantages is low toxicity at plasma concentrations reached systemically during continuous peripheral or central nervous block. The objective of this study was to test the effect of systemic ropivacaine on pain, hyperalgesia, dynamic allodynia, and flare response. METHODS: This randomized, double-blinded, placebo-controlled, crossover study was carried out in at the Clinical Trials Centre, University of Zurich, Switzerland. Twenty healthy male volunteers were included in the study. Exclusion criteria were contraindications or hypersensitivity to local anesthetics, vulnerable subjects (intellectually or mental impaired), drug, alcohol or nicotine abuse, known peripheral neuropathies, diabetes mellitus and/or congestive heart disease. Ropivacaine and saline were infused intravenously during a subcutaneous electrical stimulation. The stimulation software adjusted the stimulus strength according to the rating on a numeric rating scale (NRS; 0-10) maintaining a NRS of 5. Areas of punctate hyperalgesia, dynamic allodynia, and flare response were measured before and after the infusion. RESULTS: The area of hyperalgesia increased significantly with saline (303 +/- 380%, P < 0.05) and ropivacaine (186 +/- 137%, P < 0.05). The area of allodynia (253 +/- 299%, P < 0.05) and flare response (112 +/- 24%, P < 0.05) increased only during the placebo infusion. CONCLUSION: The results of this study imply that systemic ropivacaine may diminish pain sensitization processes. PMID- 25135388 TI - Curcumin attenuates mechanical and thermal hyperalgesia in chronic constrictive injury model of neuropathic pain. AB - INTRODUCTION: The aim of this study was to observe the effect of stress caused by neuropathic pain on serum cortisol concentration and expression of 11beta hydroxysteroid dehydrogenase type I enzyme (11betaHSD1) in spinal cord and dorsal root ganglions (DRG) and investigate the role and mechanism of curcumin in the neuropathic pain of stressful rats. Neuropathic pain is a prevalent disease that greatly impairs the patients' quality of life. A lack of the understanding of its etiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of curcumin and its effect on expression of 11beta hydroxysteroid dehydrogenase type I enzyme (11betaHSD1) in spinal dorsal horn and DRG in chronic constriction injury (CCI) mode of neuropathic pain of rats. METHODS: Seventy-two male Sprague-Dawley rats were randomized into four groups with 18 rats in each: sham operation group (Sham), chronic constrictive injury group (CCI), solvent contrast group (SC), and curcumin-treated group (Cur100). Curcumin, 100 mg/kg/day intraperitoneal, was given for 14 days starting from the first day after operation in the Cur100 group. Paw thermal withdrawal latency (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured 2 days pre-operative, and 1, 3, 5, 7, 10, and 14 days post-operative. The animals were deeply anesthetized and blood was taken from the heart, the lumbar segment (L4, 5) of the spinal cord and DRG were dissected out and homogenized. The change of cortisol was measured by enzyme-linked immunosorbent assay and the change of 11betaHSD1 expression was determined by immunochemistry and Western blot. RESULTS: Compared with sham group, PTWL and PMWT significantly decrease after operation in the CCI group; serum cortisol concentration was significantly increased and the expression of 11betaHSD1 was significantly increased in the CCI group. Comparing with CCI group, the PMWT and PTWL were increased and the serum cortisol concentration was decreased and the expression of 11betaHSD1 was inhibited in Cur100 group. CONCLUSION: Stress caused by neuropathic pain triggers release of cortisol to the blood and expression of 11betaHSD1 would increase at the same time. Curcumin could alleviate thermal and mechanical hyperalgesia induced by CCI and inhibit the serum cortisol concentration and expression of 11betaHSD1 in the spinal cord and DRG. PMID- 25135389 TI - Erratum to: Complex Regional Pain Syndrome Treated with Intravenous Immunoglobulin in a Patient with Common Variable Immune Deficiency. PMID- 25135390 TI - Molecular surveillance of the subtle septum: discovering a new mode of peptidoglycan synthesis in streptococci. AB - The process of septation requires precise temporal and spatial organization of penicillin binding proteins (PBPs) and associated proteins for the deposition of new cell wall material. In most bacteria, the filamentous protein FtsZ organises PBPs into assemblies at the midcell which then constrict inwards as peptidoglycan is synthesised, eventually closing the septa. Tsui et al. (2014), through the use of fluorescent d-amino acids and high resolution microscopy, report that PBP2x of Streptococcus pneumoniae is directed to a discrete location within the septal aperture during the later stages of cell division. Once at this new site, PBP2x catalyses the de novo synthesis of peptidoglycan, which is imaged by the authors as a central 'spot', distinct from material made by other PBPs at the outer ring. This discovery, which represents a novel mode of cell wall assembly, was made in a directed capsular knockout of strain D39, thereby avoiding potential mechanistic complications in commonly used laboratory strain R6. These findings prompt not only a partial rethink of septum formation in S. pneumoniae, but consideration of the modes of PBP localization and the subtleties that can influence phenotypic study. PMID- 25135391 TI - Lp-PLA2 Inhibitors for the Reduction of Cardiovascular Events. AB - Evidence suggests that inflammation plays a central role in the pathogenesis of atherosclerosis (Libby, Nature 420:868-874, 2002). Inflammation is a physiologic process with highly regulated and often redundant mechanisms to balance pro inflammatory and anti-inflammatory responses. The complexity of these networks has made it challenging to identify those specific pathways or key enzymes that contribute directly to atherogenesis and could act as a valuable therapeutic target. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 family of enzymes and is believed to contribute to atherosclerotic plaque progression and instability by promoting inflammation. A large number of epidemiologic studies have demonstrated that elevated levels of Lp-PLA2 are associated with an increased risk of cardiovascular events across diverse patient populations, independent of established risk factors including low-density lipoprotein cholesterol. Further, a growing number of preclinical and genetic studies support a causal role for Lp-PLA2 in atherosclerosis. The development of a novel therapeutic agent that directly inhibits the Lp-PLA2 enzyme has provided a unique opportunity to directly test the hypothesis that inhibition of this inflammatory enzyme will translate into improved clinical outcomes. In this article, we will review the evidence to support the notion that Lp-PLA2 is causally implicated in the pathobiology of atherogenesis and discuss the potential utility of inhibiting this enzyme as a therapeutic target. PMID- 25135393 TI - Coronary angiography utilization and costs for coronary artery bypass graft surgery patients in Turkey. AB - INTRODUCTION: To assess excess use of coronary angiography prior to coronary artery bypass graft surgery and its association with mortality, health care costs, and hospital quality in Turkey. METHODS: Using Turkish National Health Insurance Data (2009-2011) that included patients who underwent cardiac surgery, coronary angiography utilization was identified. Propensity score matching was used to compare survival rates and annual health care costs of patients in a coronary angiography excess-use group (>1 angiogram) and in a standard-therapy group (1 angiogram). The empirical Bayesian approach was used to combine mortality and hospital volume for quality index. The relationship between hospital quality and excess use of coronary angiography was assessed using Chi squared tests. RESULTS: Out of 20,126 patients identified, 7.27% of patients underwent excessive coronary angiography procedures (excess-use group), with an average annual cost at 9.7% higher than those who had a single angiography (standard-therapy group; P < 0.01). Operational mortality associated with excessive use was significantly higher as well (7.4% versus 5.4%, P < 0.02). There exists variation in the use of coronary angiography across cities and hospitals. Patients who underwent cardiac surgery in high-quality hospitals were less likely to have excessive angiography use than those in low-quality hospitals (7.0% versus 9.5%, P < 0.01). CONCLUSION: In Turkey, excess use of coronary angiography prior to coronary artery bypass graft surgery is associated with higher operational mortality, higher expenditures, and lower hospital quality. PMID- 25135392 TI - Anticoagulation in Patients Aged >=75 years with Atrial Fibrillation: Role of Novel Oral Anticoagulants. AB - Atrial fibrillation (AF) is an important cause of preventable, disabling stroke and is increasingly prevalent with advancing age. As life expectancies increase around the world, AF-related stroke is a growing global public health concern. Most AF patients are elderly (>=75 years old) and increasing age is a consistent independent risk factor for AF-associated stroke. Warfarin anticoagulation is highly effective for stroke prevention in AF patients, but is underutilized especially in the elderly. Although elderly patients are at increased risk of hemorrhage with oral anticoagulants, the benefit for ischemic stroke reduction exceeds the risk of hemorrhage for most elderly patients. Consequently, age alone should not be considered a contraindication for anticoagulation. Novel oral anticoagulants such as dabigatran, rivaroxaban and apixaban are at least as effective as warfarin in preventing strokes in patients with AF. Relative to warfarin, these novel agents reduce the risk of intracranial hemorrhage, the most devastating complication of anticoagulation therapy in elderly AF patients. The novel oral anticoagulants are especially appealing for stroke prevention in elderly patients with AF. PMID- 25135394 TI - Medical Costs of Oral Anticoagulants vs Warfarin for Atrial Fibrillation Patients with Different Stroke Risks. AB - INTRODUCTION: The Apixaban for the Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE), Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY), and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trials demonstrated that the oral anticoagulants (OACs), apixaban, dabigatran, and rivaroxaban, respectively, are efficacious for stroke prevention among nonvalvular atrial fibrillation (NVAF) patients. Based on clinical trial results this study evaluated medical costs of clinical events associated with use of individual OACs relative to those of warfarin in NVAF patients with moderate and high stroke risk. METHODS: Rates for primary and secondary efficacy and safety outcomes (i.e., clinical events) among NVAF patients with CHADS2 = 2 and >=3 were determined from the three OAC trials. One-year incremental costs among patients with clinical events from a US payer perspective were obtained from the literature and inflation adjusted to 2010 costs. Medical costs for clinical events associated with each OAC vs. warfarin were estimated and compared. RESULTS: For NVAF patients with moderate stroke risk (CHADS2 = 2) differences in clinical event medical costs vs. warfarin were -$298, -$143, and +$117 per patient year for apixaban, dabigatran (150 mg), and rivaroxaban, respectively (negative numbers indicate cost reduction). For NVAF patients with high stroke risk (CHADS2 >= 3) differences in clinical event medical costs vs. warfarin were -$697, +$2, and -$100 for apixaban, dabigatran (150 mg), and rivaroxaban, respectively. CONCLUSIONS: Medical cost differences associated with OACs vs. warfarin vary according to stroke risk. Of the three OACs, apixaban demonstrated consistent medical cost reductions vs. warfarin for NVAF patients with moderate and high stroke risks. PMID- 25135395 TI - StentBoost Visualization for the Evaluation of Coronary Stent Expansion During Percutaneous Coronary Interventions. AB - INTRODUCTION: Inadequate stent implantation is associated with stent thrombosis and restenosis. StentBoost can enhance stent visualization and evaluate stent expansion. Currently, there are limited comparison studies between StentBoost and intravascular ultrasound (IVUS). We aimed to test the correlation and agreement between IVUS and StentBoost measurements. METHODS: From December 2010 to December 2011, 38 patients (54 stents) were analyzed using IVUS and StentBoost. Minimal stent diameter and proximal and distal edge stent diameter were compared between imaging techniques using Pearson correlation and Bland-Altman scatter plot. RESULTS: There was good correlation between StentBoost and IVUS measurements regarding minimal stent diameter (p < 0.001 in all stent portions) and an optimal agreement between IVUS and StentBoost, while lesser agreement was found between IVUS and quantitative coronary angiography. CONCLUSION: The assessment of stent implantation using StentBoost showed an adequate correlation and agreement with IVUS. This easily applicable angiographic technique can be used to guide stent implantation. PMID- 25135396 TI - Cardiac sarcoidosis: case report, workup, and review of the literature. AB - INTRODUCTION: Cardiovascular disease is the leading cause of death worldwide, with coronary heart disease being the most common manifestation disease. While deaths attributed to coronary heart disease are falling in the developed world, the number of patients with cardiomyopathy continues to increase. In this paper, the current literature on imaging modalities for infiltrative and inflammatory cardiomyopathies is reviewed, focusing on the three most common diagnoses, namely sarcoidosis, amyloidosis, and myocarditis. CASE REPORT: A 43-year-old male presented with palpitations and left ventricular systolic dysfunction for a second opinion following an initial nondiagnostic workup. The employed clinical and radiologic approach that led to a definitive diagnosis and disease-specific treatment is presented here. CONCLUSION: The current algorithms and the strengths and weaknesses of the various radiologic techniques in establishing a diagnosis in patients who present with new onset cardiomyopathy are reviewed. Recommendations are provided regarding the selection between echocardiography, computed tomography radionuclide imaging, and magnetic resonance imaging in diagnosing the various causes of cardiomyopathy. PMID- 25135397 TI - Acute dissection of the descending aorta: a case report and review of the literature. AB - Cardiovascular disease is the leading cause of death worldwide. Acute aortic syndromes, which include aortic dissection, intramural hematoma, and penetrating aortic ulcer, represent the most morbid presentations of aortic disease and can be difficult to diagnose. Recent advances in imaging have allowed for more rapid and accurate diagnosis of acute aortic syndromes and the options for management are expanding. This case report and review presents the case of a 43-year-old man with acute type B aortic dissection who underwent two endovascular procedures for malperfusion syndrome. The review focuses on the presentation, diagnosis, medical management, and procedural options for acute dissection of the descending aorta. PMID- 25135398 TI - The medial sural artery perforator flap and its application in electrical injury to the hand. AB - We describe the use of a free medial sural artery perforator flap to reconstruct a complex composite defect to the dorsum of the right index finger following a low voltage electrical injury. The resulting defect was a 3.5 * 5 cm full thickness wound, with segmental tendon loss and loss of underlying periosteum. Due to both size and local vascular injury related to the mechanism, free tissue transfer was felt to be the most reliable option to resurface the composite defect in a single stage. The medial sural artery perforator flap, for reasons outlined below, was felt to be the best option: 1. Thin profile. 2. Vascularised fascia can be taken as a tongue, adjacent to the skin paddle: a gliding surface to prevent the tendon graft sticking to exposed bone. 3. Long pedicle: micro anastomosis away from zone of injury. 4. Little donor site morbidity: can be closed directly (if <6 cm wide) and does not require sacrifice of any major blood vessel. 5. Can be harvested with nerve and tendon from the same wound. 6. Can include as little or as much tissue required and compared to other fasciocutaneous flaps matches the texture and thickness of the hand most closely. We describe the reconstruction of the composite defect on day 42 post-injury, following one prior debridement. This case highlights the versatility and suitability of the medial sural artery flap in the reconstruction of complex hand burns with resulting composite defects. PMID- 25135399 TI - Validation of diagnosis of aplastic anaemia in La Rioja (Spain) by International Classification of Diseases codes for case ascertainment for the Spanish National Rare Diseases Registry. AB - OBJECTIVE: To analyse the validity of diagnosis of aplastic anaemia (AA) by International Classification of Diseases codes in hospital discharge data (MBDS) and the mortality registry (MR) of La Rioja to detect cases to be included in the Spanish National Rare Diseases Registry. METHODS: International Classification of Diseases (ICD) codes were used to detect AA cases during the period 2007-2012 from two administrative databases: the MBDS and the MR of La Rioja (Spain). Medical records of population selected by merging both databases were used to confirm true AA cases. The annual mean incidence rate of AA was calculated using confirmed incident cases. RESULTS: By merging both databases, 62 hypothetical AA incident patients were detected during the period 2007-2012. The medical records of the 89% of them could be revised, and they confirmed that only the 15% of the patients actually suffered AA. The annual mean AA incidence in La Rioja was 4.17 per million inhabitants (6.23 per million, males; 2.10 per million, females). CONCLUSIONS: The MBDS and the MR are not in themselves sufficient to ascertain AA cases in La Rioja and medical records should be reviewed to confirm true AA cases to be included in the Spanish National Rare Diseases Registry. PMID- 25135403 TI - [Early rehabilitation program in uncomplicated Stanford type B acute aortic dissection]. AB - Between December 2009 and August 2011, 120 patients with uncomplicated Stanford type B acute aortic dissection( UBAD) received medical treatment. In October 2010, we initiated an early rehabilitation program for UBAD patients in an acute phase. This early rehabilitation program, which was aimed at enabling the patient to walk around the ward within 2 days, was conducted for 87 consecutive patients;the remaining 33 were subjected to the conventional rehabilitation program. Mortality was not significantly different between the 2 groups. The incidence of atelectasis, need for mechanical ventilation, and intensive care unit syndrome during medical treatment occurred in 48% (16/33), 15% ( 5/33), and 30% ( 10/33), respectively, of the conventional group and in 3.4% ( 3/87), 1.1% (1/87), and 3.4% ( 3/87), respectively, of the early rehabilitation group. The outer diameter of the aorta was dilated after 4 weeks' rehabilitation in smaller percentage of patients in the early rehabilitation group than the conventional one. Thus, the early rehabilitation program was more effective for patients with UBAD than the conventional one. PMID- 25135404 TI - [Computed tomography (CT) assessment of the postoperative change of pericardial fat pad used in pulmonary surgery]. AB - The purpose of this study is to clarify the postoperative change of pericardial fat pad used in pulmonary resection to reinforce bronchial suture or bronchial stump. 5 cases who received chest computed tomography (CT) examination 2 times or more after the operation (once within one week after the operation) were enrolled. For evaluation, scoring system from 1 to 4 according to the percentage of remaining pericardial fat pad was applied(1 point: 0~19%, 2 point: 20~49%, 3 point: 50~79%, 4 point: 80~100%). At 1 to 2 months after the operation, almost all cases were 3 or 4 point. However, the scores declined to 1 or 2 point 5 months after the operation in almost all cases. It is likely that the pericardial fat pad remains to be effective in protecting bronchial stump or anastomosis 1 to 2 months after the operation. PMID- 25135405 TI - [Predictors of chronic aortic events associated with uncomplicated type B aortic dissection]. AB - OBJECTIVE: Stent-graft repair may emerge as a first-line therapy for acute complicated type B dissection(C-TBD), while debate continues over thoracic endovascular aortic repair (TEVAR) for uncomplicated type B aortic dissection (U TBD). Aggressive medical therapy, which confers a 1-year survival rate of 80-90%, is deemed appropriate for most of these patients. However, it is reported that aortic complications occur in <= 50% patients within 5 years after surgery. Subgroups of patients with U-TBD may benefit from early stent-graft placement, but identification of these patients remains difficult. Therefore, we assessed the predictors of chronic aortic events associated with U-TBD. METHODS: Between January 2001 and April 2012, 49 patients diagnosed with communicating U-TBD without aneurysm formation were admitted to our hospital. These patients were divided into 2 groups:group AC (n=25) with chronic aortic complications (aneurysm formation, aortic diameter expansion of 5 mm/0.5 year, re-dissection, and rupture) and group NC (n=24)with no aortic complications. We assessed and compared patient profiles and imaging findings between the 2 groups. RESULTS: Aortic diameter >= 40 mm was more often seen in group AC than in group NC (p=0.018). In addition, intimal tear in the distal arch was more often seen in group AC than in group NC ( p=0.002). Initial aortic diameter was significantly larger in group AC than in group NC (p=0.004). There was no significant difference in the length of communicating false lumen between the 2 groups ( p=0.107). CONCLUSIONS: Early endovascular intervention may be appropriate for U TBD in cases displaying an initial aortic diameter >= 40 mm and an initial tear in the distal arch. It is expected that randomized studies, including ADSOAB study (a study on the efficacy of endovascular grafting in uncomplicated acute dissection of the descending aorta.), will resolve the limitations of our retrospective study. PMID- 25135400 TI - P2X4 receptor regulates alcohol-induced responses in microglia. AB - Mounting evidence indicates that alcohol-induced neuropathology may result from multicellular responses in which microglia cells play a prominent role. Purinergic receptor signaling plays a key role in regulating microglial function and, more importantly, mediates alcohol-induced effects. Our findings demonstrate that alcohol increases expression of P2X4 receptor (P2X4R), which alters the function of microglia, including calcium mobilization, migration and phagocytosis. Our results show a significant up-regulation of P2X4 gene expression as analyzed by real-time qPCR (***p < 0.002) and protein expression as analyzed by flow cytometry (**p < 0.004) in embryonic stem cell-derived microglial cells (ESdM) after 48 hours of alcohol treatment, as compared to untreated controls. Calcium mobilization in ethanol treated ESdM cells was found to be P2X4R dependent using 5-BDBD, a P2X4R selective antagonist. Alcohol decreased migration of microglia towards fractalkine (CX3CL1) by 75 % following 48 h of treatment compared to control (***p < 0.001). CX3CL1-dependent migration was confirmed to be P2X4 receptor-dependent using the antagonist 5-BDBD, which reversed the effects as compared to alcohol alone (***p < 0.001). Similarly, 48 h of alcohol treatment significantly decreased phagocytosis of microglia by 15 % compared to control (*p < 0.05). 5-BDBD pre-treatment prior to alcohol treatment significantly increased microglial phagocytosis (***p < 0.001). Blocking P2X4R signaling with 5-BDBD decreased the level of calcium mobilization compared to ethanol treatment alone. These findings demonstrate that P2X4 receptor may play a role in modulating microglial function in the context of alcohol abuse. PMID- 25135406 TI - [Aortoplasty with autologous pulmonary patch for the ascending aortic stenosis after interrupted aortic arch repair]. AB - We experienced a case of ascending aortic stenosis after interrupted aortic arch repair. At the first operation in the neonatal period, diameter of the aortic annulus was 4.8 mm and no subvalvular stenosis was presented. Aortic arch was reconstructed with conventional technique of extended end-to-end anastomosis. Although ascending aortic stenosis was observed at the time, that had not been severe, however, the stenosis was exacerbated with time. At the catheterization 9 months after the operation, pressure gradient between aortic root and descending aorta was 72 mmHg. Therefore reoperation was carried out. Ascending aortoplasty using aoutologous pulmonary patch was performed. Pulmonary artery was repaired with aotologous pericardial patch. Despite mild pulmonary stenosis was observed, the postoperative course was favorable. PMID- 25135407 TI - [Maze procedure in a case of dextrocardia with atrial septal defect and persistent left superior vena cava]. AB - A 52-year-old man was diagnosed with dextrocardia at the age of 1 year and was asymptomatic until 1 year before admission. He was transferred to our hospital for management of atrial fibrillation. A transthoracic echocardiogram showed dextrocardia with atrial septal defect;moderate tricuspid valve regurgitation; and a large, persistent left superior vena cava. A cardiac catheterization study revealed that pulmonary flow/systemic flow (Qp/Qs) was 3.6 and that pulmonary vascular resistance was 2.5 Wood U.m2. Intracardiac repair with tricuspid annuloplasty and a maze procedure was scheduled. When establishing cardiopulmonary bypass, venous drainage was initially obtained from the inferior vena cava and the left superior vena cava, and the small superior vena cava was then directly cannulated after opening the right atrium. The patient's postoperative course was uneventful, and serial electrocardiograms have demonstrated maintenance of normal sinus rhythm for 3.5 years after the operation. PMID- 25135408 TI - [Coronary artery bypass grafting in a patient with chronic bird fancier's lung]. AB - Acute exacerbation is a devastating and fatal event of hypersensitivity pneumonitis. We report an 80-year-old man with chronic bird fancier's lung which acutely exacerbated after off-pump coronary artery bypass grafting. Our perioperative management included avoidance of inhalation of high concentration oxygen, administration of neutrophil elastase inhibitor, and long-term administration of antibiotics. Nevertheless, the patient experienced severe respiratory failure after influenza infection. High-resolution computed tomography (CT) showed new ground-glass opacities overlying fibrosis and traction bronchiectasis. We diagnosed acute exacerbation of hypersensitivity pneumonitis. Immediate steroid pulse therapy with empirical antibiotic administration was effective, and he recovered from critical respiratory failure. High-resolution CT was very helpful in the early detection of acute exacerbation of pneumonitis. PMID- 25135409 TI - [Surgical treatment of innominate artery aneurysm using temporary bypass to prevent cerebral ischemia]. AB - A 69-year-old woman had an innominate artery aneurysm that was adjacent to the right common carotid artery and the right subclavian artery. The patient had a dominant right vertebral artery and an underdeveloped circle of Willis. At surgery, the proximal site of the innominate artery, the right common carotid artery and the right subclavian artery were clamped with the temporary bypass between the ascending aorta and the distal site of the right brachial artery for maintaining the blood flow to the brain. The innominate artery aneurysm was resected, and a woven Dacron Y-shaped graft, 14*7 mm in diameter, was used for reconstructing the innominate artery, the right subclavian artery and the right common carotid artery. The postoperative course was uneventful and there was no postoperative neurological deficit. Temporary bypass for maintaining cerebral perfusion was useful in preventing cerebral ischemia. PMID- 25135410 TI - [Quadricuspid aortic valve; report of two cases]. AB - Quardicupid aortic valve( QAV) is a comparatively rare congenital anomaly, which presents with frequent aortic regurgitaion ( AR) due to sclerotic changes. We report 2 cases (a 67-year-old woman and a 53-year-old man) of QAV associated with AR. We made an definite diagnosis by preoperative transthoracic and intraoperative transesophageal echocardiography. Intraoperative findings showed type C QAV in case 1 and type B QAV in case 2 according to the Hurwitz classification. The left coronary ostia was slightly shifted to the aortic root in case 1. There were no other congenital anomalies, therefore only aortic valve replacement with mechanical prosthesis was performed in both cases. The postoperative courses were uneventful. PMID- 25135411 TI - [Right ventricular rupture due to blunt trauma diagnosed by MDCT; report of a case]. AB - The survival rate of cardiac rupture due to blunt trauma is generally low. We experienced a case with right ventricular rupture due to blunt trauma. The patient was a 49-year-old man who was crushed in a traffic accident and transported to a local hospital in a shock state. He was diagnosed with cardiac tamponade due to cardiac rupture, and for pericardial drainage was immediately performed. He was then transferred to our hospital for emergency surgery. His hemodynamics was stable, and he was diagnosed with right ventricular rupture by multi-detector row computed tomography (MDCT). The operation was performed successfully without cardiopulmonary bypass, and his postoperative course was uneventful. MDCT is useful for detecting the rupture site of the heart. PMID- 25135412 TI - [Thoracic endovascular aneurysm repair combined with debranching and chimney methods in a high risk patient; report of a case]. AB - We report a case of a 77-year-old man with a thoracic aortic aneurysm, combined with chronic myelomonocytic leukemia, polymyalgia rheumatica, and atial fibrillation. Open surgery was considered as high risk because he was severely ill. Instead, partial debranching and stent graft( TEVAR) were performed by chimney method. He had no major complication after surgery, and was discharged on foot on the 15th postoperative day. In high risk cases of thoracic aortic aneurysm, TEVAR with debranching and chimney methods is effective. PMID- 25135413 TI - [Endovascular stent-grafting for rupture of descending aorta with a patient with severe arterial occlusive disease; report of a case]. AB - A patient was a 63-year-old woman with poor cardiac function and systemic arterial occlusive disease, who complained of severe back pain. Computed tomography (CT) revealed a rupture of the descending aorta. Initially, abdominal aortic approach through open laparotomy was attempted, but a guide wire caused local aortic dissection. Then, after median sternotomy, endovascular stent was successfully deployed through the ascending aorta. Postoperative course was uneventful. Follow-up CT showed no endoleak. A less invasive endovascular repair would be an alternative treatment for high risk patients such as this case, but several access routes should be considered, especially in a patient with systemic arterial occlusive disease. PMID- 25135414 TI - [Mid-aortic syndrome in 2-year old boy presenting with severe left ventricular dysfunction; report of a case]. AB - Mid aortic syndrome is uncommon acquired or congenital condition characterized by segmental narrowing of the abdominal or distal descending thoracic aorta. If left untreated, it result in life threatening complications. We described the case of 2-year-old boy admitted to our hospital for hypertension and heart failure. Diagnosis of mid aortic syndrome was made with severe stenosis in distal descending aorta. With consideration of growth, we avoided bypass grafting and implantation with prothesic graft. For severe adhesion, we performed patch aortoplasty with 0.4 mm expanded polytetrafluoroethylene (ePTFE) patch. Postoperative course was unevetful. His blood pressure and left ventricular function was normalized. He was discharged on the 20st day after the surgery. PMID- 25135415 TI - [Aortic valve replacement in a patient with antiphospholipid syndrome; report of a case]. AB - A 76-year-old woman with primary antiphospholipid syndrome (APS) was referred to our hospital due to severe aortic valve stenosis. We performed aortic valve replacement using a bioprosthetic valve. Her postoperative course was uneventful. She was discharged in good health on postoperative day 33. As for cardiovascular operations in APS patients, high rates have been reported of perioperative mortality and thromboembolic and bleeding events. Perioperative management of anticoagulation must be strict. PMID- 25135416 TI - [Mitral valve replacement after previous coronary artery bypass grafting with functioning left internal thoracic artery graft: effectiveness of the method using a direct vision retrosternal approach; report of a case]. AB - Performing a redo-sternotomy when a mammary artery graft is patent can be rather difficult. We previously reported a redo-sternotomy technique involving direct visualization with a retrosternal dissection (DR) method using a Kent's retractor. The DR method in detail is as follows: 1) A midline skin incision is extended to the abdomen about 5 cm. 2) The bilateral costal arches are divided from the rectal muscle. 3). A pair of retractors is placed under the costal arch. 4) A stainless steel wire is applied to the previous sternal wire at the center of the sternum. 5) The retractor and sternal wire are lifted up using the Kent's retractor to widen the retrosternal space. 6) The sternum and sub-sternal tissue are carefully divided using an electronic scalpel or metal retractor with an entirely sternal length. 7) Routine sternotomy is performed using a Stryker. Herein, we report a patient who had undergone cardiac surgery, coronary artery bypass grafting (CABG), using a left internal mammary artery and mitral annuloplasty 2 years previously, and then developed mitral regurgitation caused by infectious endocarditis. He successfully underwent redo-sternotomy and mitral valve replacement using the DR method. In a patient with a patent internal mammary artery, the DR method greatly reduces the risk of graft injury. PMID- 25135417 TI - [Acute abdominal aortic occlusion in a patient with a giant thrombus in the left atrium and mitral stenosis; report of a case]. AB - The patient was a 69-year-old male who had had percutaneous transvenous mitral commissurotomy (PTMC) 15 years ago, and had stopped taking warfarin after PTMC. He was transferred to our emergency room( ER) because of sudden severe pain in his both lower legs. We recognized pulselessness in his both femoral arteries, and pallor, paresthesia and poikilothermia in his lower extremities. Electorocardiogram(ECG) showed arterial fibrillation, and computed tomography( CT) showed occlusion of the abdominal aorta just below inferior mesenteric artery( IMA) and both common iliac arteries. By echocardiography, a giant thrombus was detected in the left atrium with severe mitral stenosis. Thrombectomy and angioplasty were performed at about 5 hours after the onset of occlusion, and revascularization was successful. Three days after the operation, we excised the giant thrombus in the left atrium and performed mitral valve replacement because we considered that myonephropathic metabolic syndrome (MNMS) had been prevented. The postoperative course was uneventful and he was discharged on the 27th postoperative day. PMID- 25135418 TI - [Bilateral congenital coronary-pulmonary artery fistulas; report of a case]. AB - Bilateral coronary-pulmonary artery fistulas are very rare. We report a case of a 68-year-old woman without any previous medical history, who presented to our hospital after slow onset of chest heaviness on exertion. Coronary computed tomography (CT) and angiography revealed 2 fistulas:one arising from the left anterior descending artery accompanied by an aneurysm and the other from the right coronary artery. We opened the trunk of the pulmonary artery under cardio pulmonary bypass and cardiac arrest. We recognized the outflow of the shunt just above the right pulmonary cusp, which was closed from the outside. We also closed the aneurysm of the shunt. Neither the fistulas nor the aneurysm was recognized by postoperative CT. The chest symptom disappeared. PMID- 25135419 TI - [Small intestinal perforation due to metastasis from pulmonary pleomorphic carcinoma; report of a case]. AB - A 63-year-old male patient was referred to our department for an abnormal shadow in the left middle lung field. The patient underwent trans bronchial lung biopsy and pathological finding was adenocarcinoma. Computed tomography( CT) showed mass in the left lower lobe, nodules in the bilateral adrenal glands, liver, pancreas and lumbar bone. When he was admitted to our hospital for chemotherapy, chest X ray showed left pneumothorax and a chest tube was placed. Several days later, he complained of sudden abdominal pain and abdominal CT revealed free air around small intestine. Emergency operation was done and the perforation of the small intestine due to metastasis was found. He underwent partial resection of small intestine and left lower lobectomy. Pathological diagnosis was pulmonary pleomorphic carcinoma and small intestine metastasis. PMID- 25135420 TI - [Descending necrotizing mediastinitis resulting from acute epiglottitis; report of a case]. AB - Descending necrotizing mediastinitis (DNM) is a serious condition due to abscess spreading from neck into mediastinum. We report a case of DNM following acute epiglottitis and abscess. A 59-year old male visited our hospital for parotid swelling, pyrexia, and dyspnea, and was diagnosed as having acute epiglottitis at otology and hospitalized. Despite right tonsillectomy, drainage and tracheostomy on day 6 after hospitalization, he developed DNM and was referred to our department. Drainage of mediastinal regions( anterior to the trachea and tracheal bifurcation, inferoposterior mediastinum and posterior to the left main bronchus) was performed on day 14 after hospitalization. Postoperative course was uneventful. PMID- 25135421 TI - Discrete trinuclear copper(II) compounds as building blocks: the influence of the peripheral substituents on the magnetic coupling in oxamato-bridged complexes. AB - Two new trinuclear copper(ii) complexes without end-capping ligands, (Bu4N)2[Cu(dmso)2{Cu(dnopba)(dmso)}2] () and (Bu4N)2[Cu(dmso)2{Cu(dcopba)(dmso)}2] () [dnopba = 4,5-dinitro-ortho phenylenebis(oxamate), dcopba = 4,5-dichloro-ortho-phenylenebis(oxamate), Bu4N(+) = tetra-n-butylammonium and dmso = dimethylsulfoxide], were synthesized and their structures were determined by single crystal X-ray diffraction. The crystal structures of and consist of two outer bis(oxamato)(dmso)cuprate(ii) units which act as bidentate ligands toward a trans-bis(dmso)copper(ii) inner entity leading to centrosymmetric tricopper(ii) complexes with copper-copper separations across the oxamate bridges of 5.1916(3) () and 5.1776(3) A (). The peripheral copper(ii) ions in and are five-coordinate in somewhat distorted square pyramidal environments with a dmso molecule filling the apical position whereas the inner copper(ii) ion is six-coordinate in an elongated octahedral environment with two dmso molecules in the axial sites. The investigation of their magnetic properties in the temperature range 2.0-300 K shows the occurrence of a strong intramolecular antiferromagnetic coupling between the copper(ii) ions through the oxamate bridges [J1 = -296(1) () and -334(1) cm(-1) (), the Hamiltonian being defined as H = -J1(SCu2.SCu1 + SCu2.SCu1')], which leads to a low-lying spin doublet at low temperatures. Density functional theory calculations (DFT) have been used to substantiate these magnetic couplings and also to analyse the influence exerted on these interactions by the type of substituent at the 4,5 positions from the phenylene ring of the bis(oxamate) ligand. PMID- 25135422 TI - Ecotoxicological and genotoxic assessment of hospital laundry wastewaters. AB - The aim of the present study was to assess the ecotoxicity and genotoxicity of hospital laundry wastewaters generated from a regional hospital located in Rio Pardo Valley in the state of Rio Grande do Sul, Brazil. Physicochemical, microbiological, ecotoxicological, and genotoxic analyses were performed, and the results indicate that some parameters were not in accordance with the limit concentrations established by Brazilian and international guidelines for urban wastewaters. Daphnia magna (EC50 2.01%) and Danio rerio (LC50 29.25%) acute toxicity was detected, and sublethal effects were identified in Lactuca sativa (IC25 12.50%) and Allium cepa (IC25 51.25%). Cytotoxicity was observed at the five wastewater concentrations used yielding statistically significant differences (p < 0.05) in the meristematic cells of A. cepa compared with the negative control. The results obtained here warn about the necessity to develop treatment methods that can mitigate the environmental impacts caused by the ecotoxicity and genotoxicity of hospital laundry wastewaters. PMID- 25135424 TI - Variable phenotypes of sickle cell disease in India with the Arab-Indian haplotype. PMID- 25135423 TI - Combining diffusion and perfusion differentiates tumor from bevacizumab-related imaging abnormality (bria). AB - A subset of patients with high-grade glioma and brain metastases who are treated with bevacizumab develop regions of marked and persistent restricted diffusion that do not reflect recurrent tumor. Here, we quantify the degree of restricted diffusion and the relative cerebral blood volume (rCBV) within these regions of bevacizumab-related imaging abnormality (BRIA) in order to facilitate differentiation of these lesions from recurrent tumor. Six patients with high grade glioma and two patients with brain metastases who developed regions of restricted diffusion after initiation of bevacizumab were included. Six pre treatment GBM controls were also included. Restriction spectrum imaging (RSI) was used to create diffusion maps which were co-registered with rCBV maps. Within regions of restricted diffusion, mean RSI values and mean rCBV values were calculated for patients with BRIA and for the GBM controls. These values were also calculated for normal-appearing white matter (NAWM). RSI values in regions of restricted diffusion were higher for both BRIA and tumor when compared to NAWM; furthermore RSI values in BRIA were slightly higher than in tumor. Conversely, rCBV values were very low in BRIA-lower than both tumor and NAWM. However, there was only a trend for rCBV values to be higher in tumor than in NAWM. When evaluating areas of restricted diffusion in patients with high-grade glioma or brain metastases treated with bevacizumab, RSI is better able to detect the presence of pathology whereas rCBV is better able to differentiate BRIA from tumor. Thus, combining these tools may help to differentiate necrotic tissue related to bevacizumab treatment from recurrent tumor. PMID- 25135425 TI - Self-assembly: an option to nanoporous metal nanocrystals. AB - Nanoporous metal nanocrystals involving both nanoscale effects and nanopore properties hold enormous promising potential for various important applications due to their unique structures such as large surface area per unit volume and interconnected open framework. Self-assembly, as an excellent option, has been developed to control the desired structure and rational performance of nanoporous metal nanocrystals. After identifying features of their methodologies and structures, the control of synthesis based on the self-assembly technique is thoroughly discussed. The development of the self-assembly synthesis methodology is then presented in detail. The emerging application, mainly in catalysis, and corresponding design are finally summarized. PMID- 25135426 TI - Identification of microRNAs as novel biomarkers for detecting esophageal squamous cell carcinoma in Asians: a meta-analysis. AB - Accumulating evidence has suggested that microRNAs (miRNAs) may play potential role as ideal diagnostic indicators of esophageal squamous cell carcinoma (ESCC). However, previous studies have met discrepant results. Thus, we conducted this meta-analysis to assess the potential diagnostic value of miRNAs for ESCC. A systematic literature search was conducted in PubMed and other databases. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the overall test performance. The Q statistic and the I(2) test were used to assess between-study heterogeneity. The potential sources of heterogeneity were further analyzed by subgroup analyses and meta-regression. Seventeen studies from eight articles, including 995 ESCC patients and 733 healthy controls, were included in this meta-analysis. The pooled SEN and SPE were 0.81 (95% confidence interval (CI) 0.76-0.85) and 0.83 (95 % CI 0.76-0.88), respectively. The pooled PLR was 4.6 (95% CI 3.3-6.5), NLR was 0.23 (95% CI 0.19-0.29), and DOR was 20 (95% CI 13-31). The pooled AUC was 0.91 (95% CI 0.88-0.93). Subgroup analyses indicated that blood-based miRNA assay displays better diagnostic accuracy than saliva-based miRNA assay. In summary, miRNA analysis may serve as novel noninvasive biomarkers for ESCC with excellent diagnostic characteristic. In addition, subgroup analysis suggested that blood based assay yields better diagnostic characteristics than saliva-based assay. However, many issues should be managed before these findings can be translated into a clinically useful detection method for ESCC. PMID- 25135427 TI - Reproductive factors in relation to risk of brain tumors in women: an updated meta-analysis of 27 independent studies. AB - Previous studies on the association between reproductive factors and brain tumor risk in women have provided inconclusive findings. Thus, an updated meta-analysis was performed to obtain more precise risk estimates for brain tumor regarding several common reproductive factors. A comprehensive literature search for relevant publications in the PubMed and Embase databases was carried out from their inception up to June 20, 2014. Pooled relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. There were 27 independent studies with a total of 12,129 cases and 1,433,915 controls included into the present meta-analysis. We found that an elevated risk of brain tumors (RR=1.17, 95% CI 1.06-1.29, P=0.002), particularly glioma (RR=1.33, 95% CI 1.15 1.54, P<0.001), was related to older age at menarche. Interestingly, stratified analysis by type of brain tumors showed that the longer duration of breast feeding was associated with the risk of meningioma negatively but glioma positively (for meningioma: RR=0.76, 95% CI 0.64-0.91, P=0.002; for glioma: RR=1.70, 95% CI 1.14-2.55, P=0.010). No significant association was observed when estimating the roles of other reproductive factors including parity, age at first birth, menopausal status, and age at menopause in brain tumorigenesis. Our study suggests that older age at menarche is a risk factor of brain tumors and glioma in particular. Additionally, more studies are warranted to further elucidate roles and mechanisms of common reproductive factors in the risk of brain tumors. PMID- 25135429 TI - Molecular regulation of cervical cancer growth and invasion by VEGFa. AB - Although antivascular endothelial growth factor a (VEGFa) treatment has been well applied in cervical cancer therapy, the underlying molecular basis has not been precisely identified. Here, we examined the levels of VEGFa on the tumor growth and invasion in four commonly used human cervical cancer cell lines. We found that overexpression of VEGFa in these lines increased the tumor growth and invasiveness, while inhibition of VEGFa decreased the tumor growth and invasiveness. To figure out the involved signaling pathways, we applied specific inhibitors for ERK/MAPK, JNK, and PI3K/Akt signaling pathways, respectively, to VEGFa-overexpressing cervical cancer lines and found that only inhibition of PI3K/Akt signal transduction abolished VEGFa-induced increases in cell growth and invasiveness. Inhibition of Akt downstream mTor signaling similarly inhibited cell growth and invasion in VEGFa-overexpressing cervical cancer cells, suggesting that VEGFa may activate PI3K/Akt, and subsequently its downstream mTor signaling pathway, to promote cervical cancer cell growth and invasion. Furthermore, the effects of VEGFa-induced activation of mTor signaling cascades appeared to promote cancer cell growth through cyclinD1 and CDK4 activation and promote cancer cell invasion through MMP2 and MMP3. Taken together, our data suggest that anti-VEGFa treatment in cervical cancer may inhibit both tumor cell growth and invasion through PI3k/Akt/mTor signaling pathway. PMID- 25135428 TI - Down-regulation of Dicer and Ago2 is associated with cell proliferation and apoptosis in prostate cancer. AB - Dicer and Argonaute2 (Ago2) are critical components responsible not only for RNA interference but also for microRNA synthesis. The present study investigated the roles of Dicer and Ago2 in prostate cancer (Pca). First, the expression levels of Dicer and Ago2 in Pca tissues were determined by immunohistochemistry (IHC) and compared with pathological features. Next, RNA interference was used to down regulate the expression levels of Dicer and Ago2 in the Pca cell lines LNCaP, PC 3, and DU145, and effects on proliferation, apoptosis, and cell cycle were detected using the CCK-8 assay and flow cytometry, respectively. We found that Dicer and Ago2 expression levels in Pca tissues were higher than those in adjacent benign tissues and correlated with lower Gleason patterns, with the exception of Dicer expression in localized Pca. In vitro, silencing Dicer or Ago2 inhibited cell proliferation and induced apoptosis in LNCaP, PC-3, and DU145, as well as arrested the cell cycle at the G2/M phase in androgen-dependent LNCaP, or at S phase in the androgen-independent PC-3 and DU145. Altogether these findings suggest that Dicer and Ago2 play important roles in proliferation, apoptosis, and the cell cycle in Pca and might serve as both promising biomarkers for Pca progression and potential therapeutic targets. PMID- 25135430 TI - Prognostic value of TROP2 expression in patients with gallbladder cancer. AB - Altered expression of TROP2 is observed in various types of human cancers. However, the clinical significance and pathological role of TROP2 in gallbladder cancer (GBC) remains unclear. The main objective of this investigation was to clarify the relationships between TROP2 expression and the clinicopathological features of patients with GBC. Immunohistochemistry was performed to investigate the expression of TROP2 and epithelial-mesenchymal transition (EMT) indicator proteins in 93 patients with GBC. Immunohistochemistry showed that the protein expression level of TROP2 was significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that TROP2 expression was significantly correlated with histologic grade (P=0.038), tumor stage (P=0.015), and lymph node metastasis (P=0.007). Furthermore, high TROP2 expression was significantly associated with a loss of the epithelial marker E-cadherin (P=0.013) and acquisition of expression of the mesenchymal marker vimentin (P=0.031). Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between TROP2 expression and prognosis of GBC patients. Kaplan-Meier analysis indicated that patients with high TROP2 expression had poor overall survival (P<0.001). Multivariate analysis showed that high TROP2 expression was an independent predictor of overall survival. In conclusion, our data suggest for the first time that the increased expression of TROP2 in GBC is associated significantly with aggressive progression and poor prognosis. In conclusion, this study confirmed that TROP2 might be involved in regulating the EMT and malignant progression in GBC. It also provided the first evidence that TROP2 expression in GBC was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of GBC. PMID- 25135431 TI - Lgr5-positive cells are cancer stem cells in skin squamous cell carcinoma. AB - Cancer stem cells (CSCs) in most human tumors are commonly identified and enriched using similar strategies for identifying normal stem cells, including flow cytometry assays for side population, high aldehyde dehydrogenase (ALDH) activity, and CD133 positivity. Thus, development of a method for isolating a specific cancer using cancer-specific characteristic appears to be potentially important. Here, we reported extremely high Lgr5 levels in the specimen from skin squamous cell carcinoma (SCC) in patients. Using SCC cell line A431, we detected high Lgr5 and CD133 levels in ALDH-high or side population from these cancer cells. To figure out whether Lgr5 is a marker of CSCs in SCC, we transfected A431 cells with a Lgr5-creERT-2A-DTR/Cag-Loxp-GFP-STOP-Loxp-RFP plasmid and purified transfected cells (tA431) based on GFP by flow cytometry. 4-Hydroxytamoxifen (4 OHT) was given to label Lgr5-positive cells with RFP, for comparison to GFP positive Lgr5-negative cells. Lgr5-positive cells grew significantly faster than Lgr5-negative cells, and the fold increase in growth of Lgr5-positive vs Lgr5 negative cells is significantly higher than SP vs non-SP, or ALDH-high vs ALDH low, or CD133-positive vs CD133-negative cells. Moreover, in Lgr5-negative population, Lgr5-positive re-appeared in culture with time, suggesting that Lgr5 positive cells can be regenerated from Lgr5-negative cells. Furthermore, the growth of tA431 cells significantly decreased upon a single dose of diphtheria toxin (DT)/4-OHT to eliminate Lgr5-positive cell lineage, while multiple doses of DT/4-OHT nearly completely inhibited tA431 cell growth. Taken together, our data provide compelling data to demonstrate that Lgr5-positive cells are CSCs in skin SCC. PMID- 25135432 TI - A two-qubit photonic quantum processor and its application to solving systems of linear equations. AB - Large-scale quantum computers will require the ability to apply long sequences of entangling gates to many qubits. In a photonic architecture, where single-qubit gates can be performed easily and precisely, the application of consecutive two qubit entangling gates has been a significant obstacle. Here, we demonstrate a two-qubit photonic quantum processor that implements two consecutive CNOT gates on the same pair of polarisation-encoded qubits. To demonstrate the flexibility of our system, we implement various instances of the quantum algorithm for solving of systems of linear equations. PMID- 25135433 TI - Photocatalytic generation of solar fuels from the reduction of H2O and CO2: a look at the patent literature. AB - The application of photocatalysis in environment remediation as well as in the generation of useful fuels from the reduction of water (hydrogen) and of carbon dioxide (methanol, carbon monoxide and/or methane) has been investigated largely in the last four decades. A significant part (12-13%) of the literature on the generation of such fuels is found in patents. Accordingly, the present article presents a selection of the patent literature on the theme. Photocatalysts, whether pure or doped, solid solutions or composites, reported in patents are reviewed along with the corresponding preparative methods and the photocatalytic performance. The absorption of light by such materials has been extended toward the red side of the spectrum, so that a better use of solar irradiation has been obtained, but the expected improvement of the catalytic effect has not always been achieved. The causes of these results and the way for improving the performance in the various steps of the process (e.g. avoiding charge recombination or catalyst corrosion) have been documented. The correct use of the term water splitting and the fundamentals of photochemical hydrogen evolution in the presence of a sacrificial electron donor (e.g., alcohols) are discussed. Quantitative data about the amount of hydrogen evolved or carbon-based fuels produced are indicated whenever available. PMID- 25135434 TI - An evaluation of the independence of the Health of the Nation Outcome Scales. AB - OBJECTIVE: In this study the independence of the scales/items in the Health of the Nation Outcome Scales (HoNOS) was empirically investigated. METHOD: Parallel analysis using random column permutation and bootstrapping were used to compare the factor structure, intercorrelations and Cronbach's alpha from the original HoNOS study and also recently collected HoNOS ratings. Random permutation ensures that the data has the same distributions as the data it is based on, but that the variables are now independent. RESULTS: It is shown that both of the real HoNOS data sets are significantly different to the independent items data in many ways. An examination of fit statistics from confirmatory factor analysis is also used to show that the independence model is a very poor fit to the data. CONCLUSIONS: It is clear that the 12 HoNOS scales are unlikely to be independent. There is a need for more research to clarify the appropriate structure of HoNOS, and also to consider whether some of the items need either replacing or augmenting. PMID- 25135435 TI - Dosing and effectiveness of ketamine anesthesia for electroconvulsive therapy (ECT): a case series. AB - OBJECTIVE: To provide additional data about the clinical efficacy and dosing range for ketamine used as the induction agent in electroconvulsive therapy (ECT). METHOD: We reviewed the clinical data in our academic hospital ECT service over the last four years for patients who had received ketamine as the sole, or adjunctive, anesthesia induction agent. We extracted clinical data about antidepressant response as well as absolute and weight-based dosing for ketamine. RESULTS: We found nine patients who were treated with ketamine as the anesthetic at some point during the course of their treatment (eight as the sole agent, one as adjunctive). The median induction dose for ketamine was 1.1 mg/kg. For most patients, there was demonstrable clinical benefit. CONCLUSIONS: Ketamine has a role as an alternative induction anesthetic agent in ECT. Our case series adds to the literature on the concomitant use of ECT and ketamine. PMID- 25135437 TI - Medicalisation by non-medical personnel in English literature. AB - OBJECTIVE: To determine whether English literature contains depictions of medicalisation by non-medical people. METHOD: English literature was examined by us and skilled readers. RESULTS: We identified four examples: two from Macbeth and two from Vanity Fair. Not only were non-medical people the instigators, but in each publication there is one example of the advice of a medical professional (whom denied the existence of a medical problem) opinion being rejected. CONCLUSIONS: Evidence from the work of respected authors indicates that medicalisation was practiced long before it was described in the 1970s, that it may be instigated by non-medical people, and that it may continue after medical professionals deny the existence of medical problems. PMID- 25135436 TI - Madness at the movies: prioritised movies for self-directed learning by medical students. AB - OBJECTIVE: We aimed to systematically compile a list of 10 movies to facilitate self-directed learning in psychiatry by medical students. METHOD: The selected areas were those of the top five mental health conditions from the Global Burden of Disease 2010 study. The search strategy for movies covered an extensive range of sources (published literature and websites), followed by closer examination and critical viewing of a sample. RESULTS: Out of a total of 503 potential movies that were identified, 23 were selected for viewing and more detailed critique. The final top 10 were: for depressive and anxiety disorders: Ordinary People (1980), Silver Linings Playbook (2012); for illicit drug use: Trainspotting (1996), Winter's Bone (2010), Rachel Getting Married (2008), Half Nelson (2006); for alcohol use disorders: Another Year (2010), Passion Fish (1992); and for schizophrenia: The Devil and Daniel Johnston (2006), and An Angel at My Table (1990). CONCLUSIONS: The final selection of 10 movies all appeared to have relatively high entertainment value together with rich content in terms of psychiatric themes. Further research could evaluate the extent to which medical students actually watch such movies, by assessing the level of withdrawals from a medical school library and surveying student responses. PMID- 25135438 TI - Modulating the magnetic properties by structural modification in a family of Co Ln (Ln = Gd, Dy) molecular aggregates. AB - Two types of heterometallic aggregates of the general formula [(Co(II))3(Co(III))2Ln3(MU3-OH)5(O2C(t)Bu)12(L)2].2H2O (Ln = Gd(III) (), Dy(III) ()) and [(Co(III))3Ln3(MU3-OH)4(O2C(t)Bu)6(L)3](NO3)2.2CH3CN.2H2O (Ln = Gd(III) (), Dy(III) ()) were successfully isolated in reactions with [Co2(MU OH2)(O2C(t)Bu)4].(HO2C(t)Bu)4, Ln(NO3)3 and n-N-butyldiethanolamine (H2L) under ambient conditions by a change in the stoichiometry of the reactants from 1 : 1 : 1 to 1 : 1 : 2 in order. Bond Valence Sum (BVS) calculations and bond lengths indicate the presence of mixed valent Co (Co(II), Co(III)) centres in compounds and and only Co(III) centres in and as required for the charge balances and supported by the magnetic measurements. Isostructural crab shaped complexes and feature distorted cubane cores that edge share to each other whereas the metallic core of or displays hemicubane like arrangement of metal centres and oxygen atoms. Overall structural symmetry was found to enhance on moving from the former to the latter series of complexes. Magnetic studies reveal significant magnetic entropy changes for complexes and (-DeltaSm = 21.57 and 19.39 J kg(-1) K(-1)) and single molecular magnetic behaviour for and . PMID- 25135439 TI - Vaginal displacement during course of adjuvant radiation for cervical cancer: results from a prospective IG-IMRT study. AB - OBJECTIVE: To compare internal target volume (ITV) generated using population based displacements (ITV_study) with empty and full bladder scan fusion (ITV_EBFB) for organ-at-risk (OAR) doses during adjuvant intensity-modulated radiation therapy (IMRT) for cervical cancer. METHODS: From January 2011 to October 2012, patients undergoing IMRT were included. CT simulation was carried out after inserting vault markers. Planning target volume (PTV)_EBFB received 50 Gy per 25 fractions. Pre-treatment megavoltage CT (MVCT) was performed. MVCTs were registered using bony landmarks with Day 1 MVCT. Displacement of the centre of mass of markers was measured along each axis. Directional ITV was calculated using mean +/- 2 standard deviations (SDs) (ITV_study). Replanning was performed using PTV study, and OAR doses were compared with PTV_EBFB using Wilcoxon test. RESULTS: A total of 348/386 data sets were evaluable for 16 patients. The median vaginal displacement was 1.2 mm (SD, 1.3 mm), 4.0 mm (SD, 3.5 mm) and 2.8 mm (SD, 3.3 mm) in the mediolateral, superoinferior and anteroposterior directions, respectively. The ITV margins were 4.1, 10.3 and 10.6 mm. ITV_study and ITV_EBFB were 115.2 cm(3) (87.7-152.2 cm(3)) and 151 cm(3) (95.7-277.1 cm(3)) (p < 0.0001), respectively. PTV_study and PTV_EBFB were 814 and 881 cm(3) (p < 0.0001), respectively. Median doses to the bladder were lower with the PTV_study (46.2 Gy vs 43.2 Gy; p = 0.0001), and a similar trend was observed in the volume of the small bowel receiving 40 Gy (68.2 vs 60.1 cm(3); p = 0.09). CONCLUSION: Population-based PTV margins can lead to reduction in OAR doses. ADVANCES IN KNOWLEDGE: Population-based ITV may reduce OAR doses while executing adjuvant IMRT for cervical cancer. PMID- 25135440 TI - Conversion of waste polypropylene to liquid fuel using acid-activated kaolin. AB - Waste polypropylene was subjected to thermal degradation in the presence of kaolin and acid-treated kaolin, with different catalyst-to-plastics ratios, in a semi-batch reactor at a temperature range of 400-550 degrees C to obtain optimized process conditions for the production of liquid fuels. The effects of process temperature, catalyst and feed composition on yield and quality of the oil were determined. For a thermal decomposition reaction at up to 450 degrees C, the major product is volatile oil; and the major products at a higher temperature (475-550 degrees C) are either viscous liquid or wax. The highest yield of condensed fraction in the thermal reaction is 82.85% by weight at 500 degrees C. Use of kaolin and acid-treated kaolin as a catalyst decreased the reaction time and increased the yield of liquid fraction. The major product of catalysed degradation at all temperatures is highly volatile liquid oil. The maximum oil yield using kaolin and acid-treated kaolin is 87.5% and 92%, respectively, at 500 degrees C. The oil obtained was characterized using GC-MS for its composition and different fuel properties by IS methods. PMID- 25135441 TI - Paclitaxel-eluting nanofiber-covered self-expanding nonvascular stent for palliative chemotherapy of gastrointestinal cancer and its related stenosis. AB - Self-expanding non-vascular metal stents (SEMS) is now a choice of treatment for tumor-induced obstructive symptoms of gastrointestinal tract. But in-growing tumor causes re-stenosis. Here, we studied a paclitaxel-eluting nanofiber-covered stent for palliative chemotherapy of gastrointestinal cancer and its related stenosis. In vivo and in vitro feasibility of nanofiber-covered nonvascular stent was evaluated in this study. Nanofiber-covered stent released paclitaxel (PTX) in controlled manner for 30 days. PTX-NFM significantly inhibited the growth of CT 26 colon cancer in comparison with PTX injection. PTX maintained higher tumor concentrations over 1.0 MUg/ml for more than 14 days without systemic exposure. TUNEL and H&E staining proved locally concentrated PTX induced the higher apoptosis than PTX injection. In this way, PTX-eluting nanofiber-covered stent possibly inhibits in-growth of cancer and extends patency of stent. Clinical feasibility of PTX-eluting nanofiber nonvascular stent for cholangiocarcinoma and gastrointestinal cancers will be investigated in further studies. PMID- 25135442 TI - Mid- and long-term outcomes of carotid-cavernous fistula endovascular management with Onyx and n-BCA: experience of a single tertiary center. AB - INTRODUCTION: Endovascular therapy is the preferred treatment for most carotid cavernous fistulas (CCFs). Early reports have documented excellent initial clinical and radiographic outcomes after embolization of CCFs with Onyx or n butyl cyanoacrylate (n-BCA), but little evidence is available about the long-term durability of this technique. OBJECTIVE: To characterize the long-term durability of CCF liquid embolization. METHODS: The authors retrospectively reviewed a database of 24 CCFs in 21 consecutive patients who underwent Onyx or n-BCA embolization of a CCF from 2006 to 2013 at our institution. RESULTS: A total of 25 Onyx or n-BCA embolization procedures were attempted and 24 successfully completed during the study, resulting in complete or near-complete occlusion by the end of the study in all 24 CCFs (obliteration success, 100%). Attempted embolization in a single CCF failed initially, but was performed successfully at a later date by a different approach. None of the 24 CCFs recanalized, regrew, or required any further treatment subsequent to Onyx or n-BCA embolization throughout a mean 12.4 months of angiographic follow-up (range 1-36 months). Clinically significant complications were seen in three embolization procedures, including cranial nerve palsies (n=1), embolic infarct (n=1), and intraperitoneal hemorrhage (n=1). CONCLUSIONS: Early evidence has indicated that endovascular embolization with Onyx is relatively safe and effective at achieving an initial angiographic cure for CCFs. Results of our series suggest that angiographic and clinical outcomes of Onyx and n-BCA embolization remain stable at mid- and long term follow-up. PMID- 25135443 TI - Endoscopic anterior fundoplication with the Medigus Ultrasonic Surgical Endostapler (MUSETM) for gastroesophageal reflux disease: 6-month results from a multi-center prospective trial. AB - BACKGROUND: Both long-term proton pump inhibitor (PPI) use and surgical fundoplication have potential drawbacks as treatments for chronic gastroesophageal reflux disease (GERD). This multi-center, prospective study evaluated the clinical experiences of 69 patients who received an alternative treatment: endoscopic anterior fundoplication with a video- and ultrasound-guided transoral surgical stapler. METHODS: Patients with well-categorized GERD were enrolled at six international sites. Efficacy data was compared at baseline and at 6 months post-procedure. The primary endpoint was a >= 50 % improvement in GERD health-related quality of life (HRQL) score. Secondary endpoints were elimination or >= 50 % reduction in dose of PPI medication and reduction of total acid exposure on esophageal pH probe monitoring. A safety evaluation was performed at time 0 and weeks 1, 4, 12, and 6 months. RESULTS: 66 patients completed follow-up. Six months after the procedure, the GERD-HRQL score improved by >50 % off PPI in 73 % (48/66) of patients (95 % CI 60-83 %). Forty-two patients (64.6 %) were no longer using daily PPI medication. Of the 23 patients who continued to take PPI following the procedure, 13 (56.5 %) reported a >= 50 % reduction in dose. The mean percent of total time with esophageal pH <4.0 decreased from baseline to 6 months (P < 0.001). Common adverse events were peri operative chest discomfort and sore throat. Two severe adverse events requiring intervention occurred in the first 24 subjects, no further esophageal injury or leaks were reported in the remaining 48 enrolled subjects. CONCLUSIONS: The initial 6-month data reported in this study demonstrate safety and efficacy of this endoscopic plication device. Early experience with the device necessitated procedure and device changes to improve safety, with improved results in the later portion of the study. Continued assessment of durability and safety are ongoing in a three-year follow-up study of this patient group. PMID- 25135444 TI - Robotic-assisted lateral lymph node dissection for lower rectal cancer: short term outcomes in 50 consecutive patients. AB - BACKGROUND: The goal of this study was to evaluate the short-term outcomes of robotic-assisted lateral lymph node dissection for patients with advanced lower rectal cancer. METHODS: Between 2012 and 2013, 50 consecutive patients underwent robotic-assisted lateral lymph node dissection for rectal cancer in Shizuoka Cancer Center Hospital. Perioperative outcomes including operative time, operative blood loss, length of stay, postoperative complications, and histopathological data were collected prospectively. RESULTS: Median patient age was 62 years (range 36-74 years). Operative procedures included low anterior resections (n = 27), intersphincteric resections (n = 16), and abdominoperineal resections (n = 7). Bilateral lymph node dissection was performed in 44 patients. The median operative time was 476 min (range 320-683 min), and the median time required for lateral lymph node dissection was 165 min (range 85-257 min). The median blood loss was 27 mL (range 5-690 mL). There were no cases of open surgery or laparoscopic conversion. The median duration of postoperative hospital stay was 8 days (range 6-13 days). Clavien-Dindo classification Grade III-IV complications occurred in only one patient (2.0 %). There were no cases of anastomotic leak. There was no perioperative mortality. The median number of harvested lateral lymph nodes was 19 (range 5-47). CONCLUSIONS: Robotic-assisted lateral lymph node dissection is a safe, feasible, and useful approach for patients with advanced lower rectal cancer. PMID- 25135445 TI - Cranial-to-caudal approach for radical lymph node dissection along the surgical trunk in laparoscopic right hemicolectomy. AB - Complete mesocolic excision with central vascular ligation is considered to contribute to superior oncological outcomes after colon cancer surgery [1]. For advanced right-sided colon cancer, this surgery sometimes requires lymph node (LN) dissection along the superior mesenteric vein (SMV), with division of the middle colic vessels, or their right branches, at origin [2]. Here, we present cranially approached radical LN dissection along the surgical trunk during laparoscopic right hemicolectomy. The omental bursa is first opened wide, and the gastrocolic trunk of Henle is exposed, using the right gastroepiploic vessels and the accessory right colic vein (ARCV) as landmarks. After division of ARCV, SMV and middle colic vein (MCV) are identified. After dividing MCV at its root, LN dissection along SMV is conducted in a cranial-to-caudal manner. Concurrently, the middle colic artery, or its right branch, is exposed and divided at origin. The transverse colon is then raised ventrally, and LN dissection along SMV using a cranial-to-caudal approach is again performed. The ileocolic and right colic vessels are divided at origin. The ascending and transverse mesocolon, including the pedicles, are then separated from the retroperitoneal tissues, pancreatic head, and duodenum, using a medial approach. The key characteristics in this procedure consist of easy access to pancreas, early division of ARCV and middle colic vessels at origin, and easy dissection along SMV. We performed a laparoscopic colectomy using this approach for 18 patients with right-sided colon cancer. The mean operative time and blood loss were 288 min and 83 ml, respectively. The mean number of harvested LNs was 24. There were 6 cases with positive LN metastasis. There were no recurrent cases at a median follow-up period of 24 months. We consider this approach to be safe and useful for radical LN dissection along SMV for right-sided colon cancers. PMID- 25135446 TI - Ultrasound-guided laparoscopic liver resections. AB - BACKGROUND: Intraoperative liver ultrasound has an established role in liver surgery to complete staging and to guide resection. The same performances should be expected by laparoscopic ultrasound (LUS). METHODS: LUS is first performed to identify relationships between tumor and vasculo-biliary pedicles. The planes where the main vascular structures run are marked on the liver surface. Parenchymal transection is performed and each vessel recognized during LUS exploration is divided. RESULTS: From 01/2009 to 10/2013, in 61 out of 742 liver resections (8.2 %), a laparoscopic approach was attempted. The conversion rate was 9.8 % (six patients). No conversion was related to bleeding or intraoperative complications. The remnant 55 patients were affected by benign lesions in 11 cases and malignant tumors in 44. The resections included 3 left hepatectomies, 14 bisegmentectomies Sg2-3, 5 segmentectomies, and 38 wedge resections. Associated procedures were performed in eight patients (14.5 %), including four colorectal resections. Median duration of surgery was 150 min (60-345 min). Median operative blood loss was 100 mL (0-500 mL). Median size of resected tumor was 2.5 cm (0.9-8 cm). Median surgical margin in oncological resections was 7 mm (0-50 mm). Postoperative complications occurred in four patients (7.2 %), all grade 2 according to Dindo classification. No liver-related morbidity occurred. Median length of hospital stay was 5 days (3-9 days). CONCLUSIONS: Ultrasound guided liver resections can be performed by laparoscopic approach with the same accuracy than open surgery. PMID- 25135447 TI - Red blood cell folate as a risk factor for breast cancer among patients at a tertiary hospital in Uganda: a case control study. AB - BACKGROUND: Folate has been shown to play a complex but unclear role in carcinogenesis, with some studies showing that low folate intake protects against early carcinogenesis while high folate intake promotes advanced carcinogenesis. Other studies have shown that high folate is associated with decreased breast cancer risk and overall survival, yet others found no such association.This study therefore sought to determine the association between red blood folate levels and breast cancer among women seen at a tertiary Ugandan hospital. METHODS: A case control study was conducted where female patients with a histological diagnosis of breast cancer were recruited as cases, and females without cancer attending other surgical clinics as controls. Demographics and social behavior data were collected and 5 mls of blood drawn for laboratory testing of red blood cell (RBC) folate, serum vitamin B12 and RBC count. Ethical approval was obtained. RESULTS: In this study, a total of 145 women were recruited as 72 cases and 73 controls. The odds of having breast cancer among women with normal folate levels compared to those with low folate levels were 1.4 (95% CI 0.7 to 2.9) P = 0.290. Ninety participants (63%) had low RBC folate and 53 participants (37%) had normal RBC folate. Thirty five (45%) of the women from a rural setting had normal folate levels compared to 18(28%) women from an urban setting. CONCLUSIONS: There was no significant association found between RBC folate and breast cancer among this group of women in Uganda. PMID- 25135448 TI - Windrow composting mitigated CH4 emissions: characterization of methanogenic and methanotrophic communities in manure management. AB - With increasing livestock breeding, methane (CH4 ) emissions from manure management will increasingly contribute more to atmospheric CH4 concentration. The dynamics of methanogens and methanotrophs have not yet been studied in the manure environment. The current study combines surface CH4 emissions with methanogenic and methanotrophic community analyses from two management practices, windrow composting (WCOM) and solid storage (SSTO). Our results showed that there was an c. 50% reduction of CH4 emissions with WCOM compared with SSTO over a 50 day period. A sharp decrease in the quantities of both methanogens and methanotrophs in WCOM suggested that CH4 mitigation was mainly due to decreased CH4 production rather than increased CH4 oxidation. Pyrosequencing analysis demonstrated that aeration caused a clear shift of dominant methanogens in the manure, with specifically a significant decrease in Methanosarcina and increase in Methanobrevibacter. The composition of methanogenic community was influenced by manure management and regulated CH4 production. A sharp increase in the quantity of methanotrophs in SSTO suggested that microbial CH4 oxidation is an important sink for the CH4 produced. The increased abundance of Methylococcaceae in SSTO suggested that Type I methanotrophs have an advantage in CH4 oxidation in occupying niches under low CH4 and high O2 conditions. PMID- 25135449 TI - DMSO induced myocardial infarction during allogeneic cryopreserved bone marrow transplant. PMID- 25135450 TI - Early CMV replication and subsequent chronic GVHD have a significant anti leukemic effect after allogeneic HSCT in acute myeloid leukemia. AB - Early cytomegalovirus (CMV) replication (eCMV) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been suggested as an independent factor that reduces leukemia relapse risk. We retrospectively analyzed 74 patients with acute myeloid leukemia (AML) who underwent allo-HSCT between August 2006 and September 2012. All recipients were CMV seropositive. In 52 patients, eCMV occurred at a median of 35 days (range, 11-92) after allo-HSCT. Univariate analysis revealed that the factors associated with a reduction in the 5-year cumulative incidence of relapse (CIR) included the first complete remission status at allo-HSCT, non-adverse cytogenetics and molecular abnormalities, pre transplant serum ferritin level <1,400 mg/dL, chronic graft-versus-host disease (cGVHD), and eCMV. In sub-group analysis, according to the existence of eCMV and cGVHD, those with both eCMV and cGVHD showed the lowest 5-year CIR (P < 0.003). Patients with both eCMV and cGVHD had the best outcome for leukemia-free survival (LFS) (P < 0.001) and OS (P < 0.001). In the CMV-seropositive population, the presence of eCMV in combination with cGVHD had a significant positive effect on LFS and OS after allo-HSCT. When eCMV preceded cGVHD, the relapse rate after allo HSCT was significantly reduced in patients with AML. Therefore, we suggest that it is critical to have an immunological understanding of the graft-versus leukemia effect in this setting. PMID- 25135451 TI - Preexisting TP53 mutation in therapy-related acute myeloid leukemia. PMID- 25135453 TI - Optimization of niosomes for enhanced antibacterial activity and reduced bacterial resistance: in vitro and in vivo evaluation. AB - OBJECTIVE: The aim was to optimize norfloxacin niosomes for enhanced antibacterial activity and reduced bacterial resistance. METHODS: Pseudomonas aeruginosa, a biofilm forming bacterium, was used as the test organism. Different norfloxacin niosomes were evaluated in vitro and in vivo, respectively, for antibacterial activity compared with aqueous drug solution. The influence of norfloxacin niosomes on biofilm formation was investigated. The interaction of niosomes with bacterial cells was also monitored using the scanning electron microscopy (SEM). RESULTS: The efficacy of niosomes depended on their composition. Standard niosomes of Span 60 and cholesterol were similar to drug solution. Incorporation of Tween 80, oleic acid (OA), OA/propylene glycol or lecithin produced fluid niosomes which reduced the MIC and inhibited biofilm formation compared with drug solution. Incorporation of a positively charged agent into fluid niosomes enhanced the antibacterial activity and reduced biofilm formation significantly. SEM showed evidence of vesicle adsorption to the bacteria with possible adhesion or fusion with the cell membrane. The in vivo skin model confirmed the in vitro results with optimum niosomes being more efficient than drug solution. CONCLUSION: Niosomes are promising for enhanced antibacterial activity and reduced resistance to antibiotics. The later can be achieved by inhibition of biofilm formation. PMID- 25135452 TI - Role of lenalidomide in the management of myelodysplastic syndromes with del(5q) associated with pure red cell aplasia (PRCA). PMID- 25135454 TI - A psychometric evaluation of the Icelandic version of the WHO-5. AB - The psychometric properties of the Icelandic version of the World Health Organization five wellbeing index (WHO-5) were evaluated using two samples, a randomly selected sample (N = 3,896) from the Icelandic National Registry and a convenience sample of primary care patients (N = 126). The factor structure of the scale was tested with confirmatory factor analysis (CFA). The correlation between the WHO-5 and other measures of depression and anxiety were calculated to assess the scale's convergent and divergent validity. The discriminant validity of the WHO-5 was explored with a receiver operating analysis compared to the Mini International Neuropsychiatric Interview. The CFA indicated that the factor structure of the WHO-5 was one-dimensional and factorial invariant between groups. The internal reliability of the WHO-5 was adequate and the convergent, divergent and discriminant validity of the WHO-5 was supported. It is concluded that the psychometric properties of the Icelandic version of the WHO-5 are satisfactory. PMID- 25135455 TI - Testing for beneficial reversal of dominance during salinity shifts in the invasive copepod Eurytemora affinis, and implications for the maintenance of genetic variation. AB - Maintenance of genetic variation at loci under selection has profound implications for adaptation under environmental change. In temporally and spatially varying habitats, non-neutral polymorphism could be maintained by heterozygote advantage across environments (marginal overdominance), which could be greatly increased by beneficial reversal of dominance across conditions. We tested for reversal of dominance and marginal overdominance in salinity tolerance in the saltwater-to-freshwater invading copepod Eurytemora affinis. We compared survival of F1 offspring generated by crossing saline and freshwater inbred lines (between-salinity F1 crosses) relative to within-salinity F1 crosses, across three salinities. We found evidence for both beneficial reversal of dominance and marginal overdominance in salinity tolerance. In support of reversal of dominance, survival of between-salinity F1 crosses was not different from that of freshwater F1 crosses under freshwater conditions and saltwater F1 crosses under saltwater conditions. In support of marginal overdominance, between-salinity F1 crosses exhibited significantly higher survival across salinities relative to both freshwater and saltwater F1 crosses. Our study provides a rare empirical example of complete beneficial reversal of dominance associated with environmental change. This mechanism might be crucial for maintaining genetic variation in salinity tolerance in E. affinis populations, allowing rapid adaptation to salinity changes during habitat invasions. PMID- 25135456 TI - Substrate-modified functional group reactivity: hasubanan and acutumine alkaloid syntheses. AB - Functional group taxonomy provides a powerful conceptual framework to classify and predict the chemical reactivity of molecular structures. These principals are most effective in monofunctional settings, wherein individual functional groups can be analyzed without complications. In more complex settings, the predictive value of these analyses decreases as alternative reaction pathways, promoted by neighboring substituents and aggregate molecular properties, emerge. We refer to this phenomenon as substrate-modified functional group reactivity. In this Perspective, we explain how substrate-modified functional group reactivity molded our synthetic routes to the hasubanan and acutumine alkaloids. These investigations underscore the potential for discovery and insight that can only be gained by studying the reactivity of complex multifunctional structures. PMID- 25135457 TI - Interpreting carbonate and organic carbon isotope covariance in the sedimentary record. AB - Many negative delta(13)C excursions in marine carbonates from the geological record are interpreted to record significant biogeochemical events in early Earth history. The assumption that no post-depositional processes can simultaneously alter carbonate and organic delta(13)C values towards more negative values is the cornerstone of this approach. However, the effects of post-depositional alteration on the relationship between carbonate and organic delta(13)C values have not been directly evaluated. Here we present paired carbonate and organic delta(13)C records that exhibit a coupled negative excursion resulting from multiple periods of meteoric alteration of the carbonate delta(13)C record, and consequent contributions of isotopically negative terrestrial organic matter to the sedimentary record. The possibility that carbonate and organic delta(13)C records can be simultaneously shifted towards lower delta(13)C values during periods of subaerial exposure may necessitate the reappraisal of some of the delta(13)C anomalies associated with noteworthy biogeochemical events throughout Earth history. PMID- 25135458 TI - Changes in pig diet particle size profile and nutrient content during on-farm storage and distribution to the feeders. AB - The present study assessed the effect of silo emptying and feed transport by conveyor systems on particle size and nutrient content of the feed delivered to the pigs. Experiment 1 sampled feed from four feeders along the conveyor system of two barns. Samples were taken immediately after filling the feed silo (Begin) and when the silo was almost empty (End). In Experiment 2, three barns with drag type conveyors, three with auger-type conveyors and two with spiral-type conveyors were sampled. Along the different conveyors, samples at 10, 20, 50 and 85 m distance from the feed silo were taken from the feeders. In each barn, sampling was repeated for two subsequent batches of feed delivered. In all samples, particle size profile was determined and nutrient content was analysed. In Experiment 2, mineral content was also determined. In Experiment 1, the size of the different particle fractions decreased from Begin to End. An interaction (p < 0.05) between sampling time and conveyor type was detected for the 10% smallest particles. In Experiment 2, an effect of sampling time on the 10% largest particles was detected (p < 0.05). The effect of sampling time on several nutrients was observed in Experiments 1 and 2, but the affected nutrients differed between both experiments. Results implied that it was mainly emptying of the silo that affected mash particle size profile and nutrient content. The potential impact of these changes on pig performance requires further investigation. PMID- 25135459 TI - Secondary damage in left-sided frontal white matter detected by diffusion tensor imaging is correlated with executive dysfunction in patients with acute infarction at the ipsilateral posterior corona radiata. AB - BACKGROUND: Executive dysfunction has been observed in patients with left-sided anterior corona radiata infarction. However, whether left-sided posterior corona radiata infarction could cause executive dysfunction is unclear. Also, whether secondary damage in the left frontal white matter following ipsilateral posterior corona radiata infarct is causal or not and contributes to the occurrence and development of executive dysfunction, is still uncertain. METHODS: Twelve patients with posterior corona radiata infarction underwent diffusion tensor imaging (DTI) and an executive functional assessment at week 1 (W1), week 4 (W4), and week 12 (W12) after onset. Color duplex sonography and Transcranial Duplex Scanning (TCD) were performed at W1 and W12. Twelve healthy volunteers of similar ages and educational histories were examined as controls and assessed once. RESULTS: In the patients, we observed an increased mean diffusivity (MD) and a decreased fractional anisotropy (FA) in the left frontal white matter from W1 to W12. There were no significant changes in cerebral blood flow in patients between W1 and W12 according to the result of Color duplex sonography and TCD. Patients showed progressively impaired executive function during 12 weeks. Significant correlations were found between increased MD and decreased FA in the left frontal white matter with impaired degree of executive function. CONCLUSIONS: This study demonstrates that DTI detected secondary damage in left-sided frontal white matter in patients with acute infarction at the ipsilateral posterior corona radiata. This change may be correlated with executive functional changes in these patients. PMID- 25135460 TI - Panoramic radiography measurements, osteoporosis diagnoses and fractures in Japanese men and women. AB - OBJECTIVES: The purpose of this study was to investigate the association of the shape of the mandibular cortex on panoramic radiographs with the risk of an osteoporosis diagnosis without prevalent fractures and with the risk of osteoporotic fractures in Japanese men and women. SUBJECTS AND METHODS: One thousand and twenty-one subjects aged 40-89 years, who visited our university hospital and underwent panoramic radiography between 2007 and 2013, participated in this study. Eighty-eight patients received a diagnosis of osteoporosis without prevalent fractures, and 55 were diagnosed with osteoporotic fractures. Blinded to the groupings, we classified the shape of the mandibular cortex on panoramic radiographs as normal, moderately eroded or severely eroded. RESULTS: After adjustment for confounding factors, the odds ratios for an osteoporosis diagnosis associated with moderately eroded and severely eroded mandibular cortices were 1.4 (95% CI, 0.8-2.6) and 2.6 (95% CI, 1.4-5.0), respectively. The odds ratios for an osteoporotic fracture associated with moderately eroded and severely eroded cortices were 0.8 (95% CI, 0.4-1.7) and 1.1 (95% CI, 0.5-2.5), respectively. CONCLUSIONS: Subjects in Japan with eroded mandibular cortices tended to be at increased risk of osteoporosis diagnoses but not of fractures. PMID- 25135461 TI - Late toxicity of proton beam therapy for patients with the nasal cavity, para nasal sinuses, or involving the skull base malignancy: importance of long-term follow-up. AB - BACKGROUND: Although several reports have shown that proton beam therapy (PBT) offers promise for patients with skull base cancer, little is known about the frequency of late toxicity in clinical practice when PBT is used for these patients. Here, we conducted a retrospective analysis to clarify the late toxicity profile of PBT in patients with malignancies of the nasal cavity, para nasal sinuses, or involving the skull base. METHODS: Entry to this retrospective study was restricted to patients with (1) malignant tumors of the nasal cavity, para-nasal sinuses, or involving the skull base; (2) definitive or postoperative PBT (>50 GyE) from January 1999 through December 2008; and (3) more than 1 year of follow-up. Late toxicities were graded according to the common terminology criteria for adverse events v4.0 (CTCAE v4.0). RESULTS: From January 1999 through December 2008, 90 patients satisfied all criteria. Median observation period was 57.5 months (range, 12.4-162.7 months), median time to onset of grade 2 or greater late toxicity except cataract was 39.2 months (range, 2.7-99.8 months), and 3 patients had toxicities that occurred more than 5 years after PBT. Grade 3 late toxicities occurred in 17 patients (19%), with 19 events, and grade 4 late toxicities in 6 patients (7%), with 6 events (encephalomyelitis infection 2, optic nerve disorder 4). CONCLUSIONS: In conclusion, the late toxicity profile of PBT in patients with malignancy involving the nasal cavity, para-nasal sinuses, or skull base malignancy was partly clarified. Because late toxicity can still occur at 5 years after treatment, long-term follow-up is necessary. PMID- 25135463 TI - 'Bio-load' and bio-type profiles of Mycobacterium avium subspecies paratuberculosis infection in the domestic livestock population endemic for Johne's disease: a survey of 28 years (1985-2013) in India. AB - Bio-load and bio-profile of Mycobacterium avium subspecies paratuberculosis was studied in the domestic livestock population of the country. Of the 23,429 farm and farmer's animals screened, average bio-load was 23.3% (Period of study; 28 years for goats; 13 years for sheep, cattle and buffaloes). Species-wise, bio load was 20.1, 32.7, 39.3 and 28.3% in goats, sheep, cattle and buffaloes, respectively. Bio-load was significantly lower in time period A (P < 0.001) and B (P < 0.03), compared with period C. Geographical zone-wise, bio-load of MAP was significantly higher (P < 0.05) in Central zone compared with South, West, East and North zones. Bio-load in 11 states ranged from 16.2 to 87.8%. Of 8450, 5643, 8185 and 1151 samples screened by microscopy, culture, indigenous ELISA and IS900 blood PCR, 20.0, 10.6, 35.1 and 26.6% samples were positive, respectively. Bio load was 32.8 and 31.6% in farm and farmer's goats and sheep, respectively, and 62.1% in farmer's cattle. MAP bio-load was also monitored in four farm units (three goats and one sheep) for breed improvement and three farm goats units for experimental purposes at Central Institute for Research on Goats in Mathura district. Of the 8025 goats and 1525 sheep that died from 1988 to 2013, 10.9 and 3.0% deaths were due to JD, respectively. On the basis of JD and suspected JD, 10.0 and 28.4% goats and 2.2 and 40.9% sheep, respectively were culled from the farm units in 25 years. Microscopic examination of 214 tissues (mesenteric lymph nodes and intestines) of 107 animals, it was observed that bio-load of MAP was high (25.0-60.0%) in farm animals. 'Indian Bison Type' was the dominant biotype, irrespective of domestic livestock species and the geographical zone. PMID- 25135462 TI - Next-generation prostate-specific antigen test: precursor form of prostate specific antigen. AB - An urgent need exists to develop a more sophisticated screening system in order to improve diagnostic accuracy of clinically significant cancer and also to reduce the drawbacks of prostate-specific antigen (PSA) screening including overdetection and overtreatment. The most promising next-generation PSA test, which can improve the management of prostate cancer, may be proenzyme PSA (proPSA) or precursor PSA (pPSA). proPSA has pro-leader peptide sequences of seven or less amino acids and previous studies demonstrated that [-2]proPSA, which contains only a 2-amino-acid propeptide leader, could be more useful not only to distinguish between men with and without cancer, but also between tumors with aggressive features with performance exceeding other classical PSA-related indices including ratio of free PSA to total PSA (%f-PSA) and PSA density. Recently, it was demonstrated that baseline [-2]proPSA-related indices were independent factors to predict pathological reclassification at one year or several years after entering active surveillance. Furthermore, a retrospective study suggested that [-2]proPSA might be a useful predictive marker for future developing clinically manifested prostate cancer as well as aggressive tumors. ProPSA-related indices may have the potential for developing a more ideal risk classification for men at risk for prostate cancer, with a screening system maintaining the sensitivity of detecting clinically significant prostate cancer while saving cost, individualized treatment strategies, and follow-up procedures of active surveillance or active treatments. At a minimum, proPSA will be one of the most important new markers on the prostate cancer management in the near future. PMID- 25135464 TI - Partial genetic characterization of peste des petits ruminants virus from goats in northern and eastern Tanzania. AB - Peste des petits ruminants (PPR) is an acute viral disease of small ruminants. The disease was first reported in Tanzania in 2008 when it was confined to the Northern Zone districts bordering Kenya. The present study was carried out to confirm the presence of PPR virus (PPRV) in Tanzania and to establish their phylogenetic relationships. Samples (oculonasal swabs, tissues and whole blood) were obtained from live goats with clinical presentation suggestive of PPR and goats that died naturally in Ngorongoro (Northern Tanzania) and Mvomero (Eastern Tanzania) districts. The clinical signs observed in goats suspected with PPR included fever, dullness, diarrhea, lacrimation, matting of eye lids, purulent oculonasal discharges, cutaneous nodules, erosions on the soft palate and gums and labored breathing. Post mortem findings included pneumonia, congestion of the intestines, and hemorrhages in lymph nodes associated with the respiratory and gastrointestinal systems. PPRV was detected in 21 out of 71 tested animals using primers targeting the nucleoprotein (N) gene. Phylogenetic analysis, based on the N gene, indicated that PPRV obtained from Northern and Eastern Tanzania clustered with PPRV strains of Lineage III, together with PPRV from Sudan and Ethiopia. The findings of this study indicate that there are active PPRV infections in Northern and Eastern Tanzania, suggesting risks for potential spread of PPR in the rest of Tanzania. PMID- 25135465 TI - Leptospirosis in cattle: a challenging scenario for the understanding of the epidemiology. AB - All over the world, leptospirosis has been reported as one of the major causes of reproductive failure in cattle and other ruminants, determining abortions, stillbirth, weak newborns and decrease in their growth rate and milk production. Nevertheless, despite its importance, it is still a challenging disease, from what scarce information about epidemiology, prophylaxis and control is available nowadays. During the last decades of the last century, many epidemiological studies have been conducted in several countries, mainly based on serology. According to those studies, a seroepidemiological scenario has been stated for different regions, where different serovars were reported for cattle. Nevertheless, a huge problem is that, when efforts are made in order to increase the collection of local strains (isolates), it has been demonstrated that the scenario that emerges from those studies contrasts with those previously determined by serology. Despite the large number of serological studies worldwide, the number of isolates is scarce. Isolation technique is a very delicate procedure that needs no contamination, fast processing and long delay to produce a positive result, what may corroborate to the lack of information for the comparison between serology versus bacteriological data, mainly in developing countries. It is noteworthy that the epidemiological scenario now acknowledged may not represent what really occurs in many parts of the world, particularly on those tropical regions where the disease is endemic. Consequently, the current knowledge about epidemiology and control, as well as the available diagnostic tools and the commercial vaccines, may not be adequate for those regions, what leads to a frustrating scenario of endemicity and difficulties on the control of the disease. Without a huge effort in the culturing of local strains, besides the advances on molecular typing, leptospirosis will not be defeated and will probably remain endemic in the developing countries, leading to important economic hazards in animal production and risks to public health in those regions. PMID- 25135466 TI - Predominance of genotype 1.1 and emergence of genotype 2.2 classical swine fever viruses in north-eastern region of India. AB - Classical swine fever (CSF) is a highly contagious and the most important disease of pigs worldwide.CSF is enzootic in pig herds in India and continues to cause huge economic losses to pig farmers. Nearly 40% of the total pig population of India is present in the north-eastern (NE) states where pig husbandry plays an important role in the socio-economic development. Pigs reared in the backyards are the only source of livelihood for a majority of poor tribal population in the region. Hardly any CSF vaccination is currently being undertaken in the unorganized pig farming in the NE region due to economic reasons and vaccine unavailability. A thorough understanding of the current epidemiological status of CSF is essential for the effective control of the disease in the NE region. Hence, we carried out molecular characterization of CSFV isolates from field outbreaks during 2011-2012 in the entire north-eastern region of India to establish the genetic groups of prevalent CSF viruses in the region. A total of 17 CSFV isolates obtained from different parts of the NE region were characterized by comparing the sequences of three partial genomic regions of the virus, that is 150 nt of 5' UTR, 190 nt of E2 and 409 nt of NS5B. Of the 17 CSFV isolates, 15 isolates belonged to 1.1 (88.2%) and two isolates (11.8%) belonged to 2.2 subgenogroup. The genogroup 2.2 CSFV were associated with outbreaks in Arunachal Pradesh that shares international borders with Bhutan, Myanmar and China. Genogroup 2.2 CSFV isolated in the present study shared high level of sequence similarity with 2.2 viruses form China, raising the possibility of virus incursion from this region. In summary, we found a continued predominance of 1.1 subgroup and an emergence of 2.2 subgroup CSFV in NE region of India. PMID- 25135467 TI - Epidemiology of viral pathogens of free-ranging dogs and Indian foxes in a human dominated landscape in central India. AB - There is an increasing concern that free-ranging domestic dog (Canis familiaris) populations may serve as reservoirs of pathogens which may be transmitted to wildlife. We documented the prevalence of antibodies to three viral pathogens, canine parvovirus (CPV), canine distemper virus (CDV) and canine adenovirus (CAV), in free-ranging dog and sympatric Indian fox (Vulpes bengalensis) populations in and around the Great Indian Bustard Wildlife Sanctuary, in Maharashtra, central India. A total of 219 dogs and 33 foxes were sampled during the study period. Ninety-three percentage of dogs and 87% of foxes were exposed to one or more of the three pathogens. Exposure rates in dogs were high: >88% for CPV, >72% for CDV and 71% for CAV. A large proportion of adult dogs had antibodies against these pathogens due to seroconversion following earlier natural infection. The high prevalence of exposure to these pathogens across the sampling sessions, significantly higher exposure rates of adults compared with juveniles, and seroconversion in some unvaccinated dogs documented during the study period suggests that these pathogens are enzootic. The prevalence of exposure to CPV, CDV and CAV in foxes was 48%, 18% and 52%, respectively. Further, a high rate of mortality was documented in foxes with serologic evidence of ongoing CDV infection. Dogs could be playing a role in the maintenance and transmission of these pathogens in the fox population, but our findings show that most dogs in the population are immune to these pathogens by virtue of earlier natural infection, and therefore, these individuals make little current or future contribution to viral maintenance. Vaccination of this cohort will neither greatly improve their collective immune status nor contribute to herd immunity. Our findings have potentially important implications for dog disease control programmes that propose using canine vaccination as a tool for conservation management of wild carnivore populations. PMID- 25135469 TI - Epidemiology of pulmonary hypertension and right ventricular failure in left heart failure. AB - Pulmonary hypertension (PH) leading to right ventricular failure (RVF) is a common complication of left heart failure irrespective of the left ventricular ejection fraction. PH due to left heart disease is the most common cause of PH. The prevalence of PH and RVF in left heart failure varies depending on the patient population studied, the method used to diagnose PH, and the hemodynamic criteria used to define PH. Elevated left-sided filling pressure and functional mitral regurgitation are the two major determinants of PH in left heart failure. PH is associated with markers of disease severity, advanced symptoms, and worse long-term outcomes including heart failure hospitalization and mortality in left heart failure. RVF has independent, incremental prognostic value over PH for adverse outcomes in left heart failure. PH and RVF may be potential therapeutic targets in patients with left heart failure. PMID- 25135468 TI - White matter involvement in chronic musculoskeletal pain. AB - There is emerging evidence that chronic musculoskeletal pain is associated with anatomic and functional abnormalities in gray matter. However, little research has investigated the relationship between chronic musculoskeletal pain and white matter. In this study, we used whole-brain tract-based spatial statistics and region-of-interest analyses of diffusion tensor imaging data to demonstrate that patients with chronic musculoskeletal pain exhibit several abnormal metrics of white matter integrity compared with healthy controls. Chronic musculoskeletal pain was associated with lower fractional anisotropy in the splenium of the corpus callosum and the left cingulum adjacent to the hippocampus. Patients also had higher radial diffusivity in the splenium, right anterior and posterior limbs of the internal capsule, external capsule, superior longitudinal fasciculus, and cerebral peduncle. Patterns of axial diffusivity (AD) varied: patients exhibited lower AD in the left cingulum adjacent to the hippocampus and higher AD in the anterior limbs of the internal capsule and in the right cerebral peduncle. Several correlations between diffusion metrics and clinical variables were also significant at a P < .01 level: fractional anisotropy in the left uncinate fasciculus correlated positively with total pain experience and typical levels of pain severity. AD in the left anterior limb of the internal capsule and left uncinate fasciculus was correlated with total pain experience and typical pain level. Positive correlations were also found between AD in the right uncinate and both total pain experience and pain catastrophizing. These results demonstrate that white matter abnormalities play a role in chronic musculoskeletal pain as a cause, a predisposing factor, a consequence, or a compensatory adaptation. PERSPECTIVE: Patients with chronic musculoskeletal pain exhibit altered metrics of diffusion in the brain's white matter compared with healthy volunteers, and some of these differences are directly related to symptom severity. PMID- 25135471 TI - Experience of mechanical thrombectomy for paediatric arterial ischaemic stroke. AB - BACKGROUND: Paediatric arterial ischaemic stroke (AIS) is an important cause of acute neurological symptoms in children, it causes significant morbidity and is one of the top ten causes of childhood deaths. Consensus papers have suggested guidelines for the management of AIS in childhood, although none recommend thrombectomy. Despite this, children within our institution have undergone mechanical thrombectomy for large vessel occlusion. This is the first series of mechanical thrombectomy and outcomes performed in children in the U.K. METHODS: We describe the endovascular management of paediatric arterial ischaemic stroke (AIS) in four children (5-15 years) with PedNIHSS > 17. RESULTS: Three had basilar artery (BA) occlusion and one left middle cerebral artery (MCA) occlusion. All underwent uncomplicated thrombectomy followed by intravenous heparin. One had a successful second attempt. The BA cases underwent thrombectomy 17-36 h after symptom onset; the left MCA case <6 h after symptom onset. Modified Rankin Scale (MRS) was 0-3, 50% had MRS 0. DISCUSSION: Adult AIS guidelines recommend IV recombinant tissue plasminogen activator (r-tPA) within 4.5 h of onset and intra-arterial r-tPA within 6 h; thrombectomy being reserved for carefully selected patients. Paediatric AIS recognition is problematic, often with delayed imaging. There is little evidence regarding efficacy of thrombectomy for paediatric AIS. Our experience suggests there may be a role for endovascular clot retrieval in selected patients managed by an experienced multidisciplinary team. Careful data collection is mandatory. PMID- 25135470 TI - The acute cardiorenal syndrome: burden and mechanisms of disease. AB - Worsening renal function during the treatment of acute decompensated heart failure, so-called acute cardio-renal syndrome, is very common and complicates the treatment course. The underlying pathophysiology of worsening renal function (WRF) involves variable contributions of renal hemodynamics, neurohormonal activity, and oxidative stress. Historically, WRF has been associated with adverse outcomes. However, emerging data support therapeutic strategies that permit WRF while effectively treating congestion as they are associated with improved outcomes. PMID- 25135472 TI - Prenatal evaluation and postnatal early outcomes of fetal ventriculomegaly. AB - OBJECTIVE: This study aims to determine the incidence, etiology, diagnostic criteria and early outcomes of prenatally diagnosed fetal ventriculomegaly (VM). METHODS: Diagnostic criteria for the fetal VM was atrial diameter of lateral ventricle measuring >=10 mm, independent from gestational age. Results of our patients from ultrasonography (USG), karyotyping, congenital infections, and associated abnormalities were noted. Progress during pregnancy, postnatal USG results and neurobehavioral outcomes were recorded. RESULTS: In our study, 40 subjects of fetal VM were recorded. 16 and 24 of those were bilateral (40%) and unilateral (60%) respectively. Female to male fetus ratio was 19/21 (0.9). Median gestational age at the diagnosis was 22 weeks (ranging between 16 and 34 weeks). While 21 VM subjects were isolated (52.5%) only 19 of the total were shown associated structural abnormalities in (47.5%) in addition to VM. Toxoplasmosis were diagnosed only in one subject (2.5%). Nineteen subjects had amniocentesis (47.5%) and 2 of them were showed abnormalities (10.5%) as follows; "inversion and duplication 8 (p11.2p23)" and "deletion 3". VM got back in to normal size during pregnancy in 24 subjects (24/40, 60%). Eight pregnancies were terminated (8/40) (20%). Five babies passed away during neonatal and postneonatal period. Some other structural abnormalities were diagnosed after the birth at six babies who classified as mild "isolated" VM. CONCLUSIONS: Our study revealed that amongst mild VM subjects, incidence of associated abnormalities and termination rate were higher. Although most of mild VM subjects are thought to be benign, associated abnormalities should be carefully evaluated and determined pre- and postnatally. PMID- 25135473 TI - Evaluation of Gram-negative bacterial infection by a stable and conjugative bioluminescence plasmid in a mouse model. AB - BACKGROUND: The green fluorescence protein (GFP)-associated fluorescence method and the luciferase-associated bioluminescence method are the two major methods for IVIS imaging system to investigate the bacterial infection in animal models. The aim of this study was to evaluate the infection route of Gram-negative bacteria carrying a stable and broad range of conjugative bioluminescence plasmid pSE-Lux1 in a mouse model. RESULTS: Both encapsulated and non-encapsulated Gram negative bacteria were used as hosts to evaluate conjugation efficiency and plasmid stability of pSE-Lux1, a recombinant of pSE34 and luxABCDE operon. The plasmid conjugation efficiencies of pSE-Lux1 ranged from 10-3 to 10-7 in various Gram-negative bacteria. Plasmid pSE-Lux1 maintained in Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovars Choleraesues (abbreviated S. Choleraesuis) and Typhimurium (S. Typhimurium), than in Acinetobacter baumannii and Serratia marcescens, was shown to be of better stability for at least four days. To investigate systemic bacterial infections, K. pneumoniae strain CG354 was intravenously injected, and then was clearly observed to be non pathogenic to Balb/c mice for a long-term bioluminescence monitoring for 6 days. For examining dynamic distributions of gastrointestinal tract infection, the invasion protein SipB-deficient mutant OU5045?sipB and OU5046?sipB of S. serovar Typhimurium constructed in this study, compared to wild-type strain OU5045 and its virulence plasmid-less strain OU5046, were of less virulence to mice. CONCLUSIONS: This is the first study to evaluate the conjugative and stable bioluminescence vehicle system of pSE-Lux1 in a wide range of Gram-negative bacteria, a system that can provide a useful reporter approach to trace systemic and gastrointestinal bacterial infections in a mouse model. PMID- 25135475 TI - CTCF controls HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure in NT2/D1 cells. AB - HOX cluster genes are activated sequentially in their positional order along the chromosome during vertebrate development. This phenomenon, known as temporal colinearity, depends on transcriptional silencing of 5' HOX genes. Chromatin looping was recently identified as a conserved feature of silent HOX clusters, with CCCTC-binding factor (CTCF) binding sites located at the loop bases. However, the potential contribution of CTCF to HOX cluster silencing and the underlying mechanism have not been established. Here, we demonstrate that the HOXA locus is organized by CTCF into chromatin loops and that CTCF depletion causes significantly enhanced activation of HOXA3 to -A7, -A9 to -A11, and -A13 in response to retinoic acid, with the highest effect observed for HOXA9. Our subsequent analyses revealed that CTCF facilitates the stabilization of Polycomb repressive complex 2 (PRC2) and trimethylated lysine 27 of histone H3 (H3K27me3) at the human HOXA locus. Our results reveal that CTCF functions as a controller of HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin structure. PMID- 25135474 TI - Efficient mRNA polyadenylation requires a ubiquitin-like domain, a zinc knuckle, and a RING finger domain, all contained in the Mpe1 protein. AB - Almost all eukaryotic mRNAs must be polyadenylated at their 3' ends to function in protein synthesis. This modification occurs via a large nuclear complex that recognizes signal sequences surrounding a poly(A) site on mRNA precursor, cleaves at that site, and adds a poly(A) tail. While the composition of this complex is known, the functions of some subunits remain unclear. One of these is a multidomain protein called Mpe1 in the yeast Saccharomyces cerevisiae and RBBP6 in metazoans. The three conserved domains of Mpe1 are a ubiquitin-like (UBL) domain, a zinc knuckle, and a RING finger domain characteristic of some ubiquitin ligases. We show that mRNA 3'-end processing requires all three domains of Mpe1 and that more than one region of Mpe1 is involved in contact with the cleavage/polyadenylation factor in which Mpe1 resides. Surprisingly, both the zinc knuckle and the RING finger are needed for RNA-binding activity. Consistent with a role for Mpe1 in ubiquitination, mutation of Mpe1 decreases the association of ubiquitin with Pap1, the poly(A) polymerase, and suppressors of mpe1 mutants are linked to ubiquitin ligases. Furthermore, an inhibitor of ubiquitin-mediated interactions blocks cleavage, demonstrating for the first time a direct role for ubiquitination in mRNA 3'-end processing. PMID- 25135476 TI - Regulation of the death-associated protein kinase 1 expression and autophagy via ATF6 requires apoptosis signal-regulating kinase 1. AB - The death-associated protein kinase 1 (DAPK1) is an important regulator of cell death and autophagy. Recently, we have identified that ATF6, an endoplasmic reticulum-resident transcription factor, in association with the transcription factor CEBP-beta, regulates the gamma interferon (IFN-gamma)-induced expression of Dapk1 (P. Gade et al., Proc. Natl. Acad. Sci. U. S. A. 109:10316-10321, 2012, doi.org/10.1073/pnas.1119273109). IFN-gamma-induced proteolytic processing of ATF6 and phosphorylation of C/EBP-beta were essential for the formation of a novel transcriptional complex that regulates DAPK1. Here, we report that IFN gamma activates the ASK1-MKK3/MKK6-p38 mitogen-activated protein kinase (MAPK) pathway for controlling the activity of ATF6. The terminal enzyme in this pathway, p38 MAPK, phosphorylates a critical threonine residue in ATF6 upstream of its DNA binding domain. ATF6 mutants defective for p38 MAPK phosphorylation fail to undergo proteolytic processing in the Golgi apparatus and drive IFN-gamma induced gene expression and autophagy. We also show that mice lacking Ask1 are highly susceptible to lethal bacterial infection owing to defective autophagy. Together, these results identify a novel host defense pathway controlled by IFN gamma signaling. PMID- 25135477 TI - FANCD2-controlled chromatin access of the Fanconi-associated nuclease FAN1 is crucial for the recovery of stalled replication forks. AB - Fanconi anemia (FA) is a cancer predisposition syndrome characterized by cellular hypersensitivity to DNA interstrand cross-links (ICLs). Within the FA pathway, an upstream core complex monoubiquitinates and recruits the FANCD2 protein to ICLs on chromatin. Ensuing DNA repair involves the Fanconi-associated nuclease 1 (FAN1), which interacts selectively with monoubiquitinated FANCD2 (FANCD2(Ub)) at ICLs. Importantly, FANCD2 has additional independent functions: it binds chromatin and coordinates the restart of aphidicolin (APH)-stalled replication forks in concert with the BLM helicase, while protecting forks from nucleolytic degradation by MRE11. We identified FAN1 as a new crucial replication fork recovery factor. FAN1 joins the BLM-FANCD2 complex following APH-mediated fork stalling in a manner dependent on MRE11 and FANCD2, followed by FAN1 nuclease mediated fork restart. Surprisingly, APH-induced activation and chromatin recruitment of FAN1 occur independently of the FA core complex or the FAN1 UBZ domain, indicating that the FANCD2(Ub) isoform is dispensable for functional FANCD2-FAN1 cross talk during stalled fork recovery. In the absence of FANCD2, MRE11 exonuclease-promoted access of FAN1 to stalled forks results in severe FAN1 mediated nucleolytic degradation of nascent DNA strands. Thus, FAN1 nuclease activity at stalled replication forks requires tight regulation: too little inhibits fork restart, whereas too much causes fork degradation. PMID- 25135479 TI - Biotechnological challenges of bioartificial kidney engineering. AB - With the world-wide increase of patients with renal failure, the development of functional renal replacement therapies have gained significant interest and novel technologies are rapidly evolving. Currently used renal replacement therapies insufficiently remove accumulating waste products, resulting in the uremic syndrome. A more preferred treatment option is kidney transplantation, but the shortage of donor organs and the increasing number of patients waiting for a transplant warrant the development of novel technologies. The bioartificial kidney (BAK) is such promising biotechnological approach to replace essential renal functions together with the active secretion of waste products. The development of the BAK requires a multidisciplinary approach and evolves at the intersection of regenerative medicine and renal replacement therapy. Here we provide a concise review embracing a compact historical overview of bioartificial kidney development and highlighting the current state-of-the-art, including implementation of living-membranes and the relevance of extracellular matrices. We focus further on the choice of relevant renal epithelial cell lines versus the use of stem cells and co-cultures that need to be implemented in a suitable device. Moreover, the future of the BAK in regenerative nephrology is discussed. PMID- 25135478 TI - TPC1 has two variant isoforms, and their removal has different effects on endo lysosomal functions compared to loss of TPC2. AB - Organelle ion homeostasis within the endo-lysosomal system is critical for physiological functions. Two-pore channels (TPCs) are cation channels that reside in endo-lysosomal organelles, and overexpression results in endo-lysosomal trafficking defects. However, the impact of a lack of TPC expression on endo lysosomal trafficking is unknown. Here, we characterize Tpcn1 expression in two transgenic mouse lines (Tpcn1(XG716) and Tpcn1(T159)) and show expression of a novel evolutionarily conserved Tpcn1B transcript from an alternative promoter, raising important questions regarding the status of Tpcn1 expression in mice recently described to be Tpcn1 knockouts. We show that the transgenic Tpcn1(T159) line lacks expression of both Tpcn1 isoforms in all tissues analyzed. Using mouse embryonic fibroblasts (MEFs) from Tpcn1(-/-) and Tpcn2(-/-) animals, we show that a lack of Tpcn1 or Tpcn2 expression has no significant impact on resting endo lysosomal pH or morphology. However, differential effects in endo-lysosomal function were observed upon the loss of Tpcn1 or Tpcn2 expression; thus, while Tpcn1(-/-) MEFs have impaired trafficking of cholera toxin from the plasma membrane to the Golgi apparatus, Tpcn2(-/-) MEFs show slower kinetics of ligand induced platelet-derived growth factor receptor beta (PDGFRbeta) degradation, which is dependent on trafficking to lysosomes. Our findings indicate that TPC1 and TPC2 have important but distinct roles in the endo-lysosomal pathway. PMID- 25135480 TI - Infrared and Raman spectroscopic investigation of the reaction mechanism of cytochrome c oxidase. AB - Recent progress in studies on the proton-pumping and O2reduction mechanisms of cytochrome c oxidase (CcO) elucidated by infrared (IR) and resonance Raman (rR) spectroscopy, is reviewed. CcO is the terminal enzyme of the respiratory chain and its O2reduction reaction is coupled with H+ pumping activity across the inner mitochondrial membrane. The former is catalyzed by heme a3 and its mechanism has been determined using a rR technique, while the latter used the protein moiety and has been investigated with an IR technique. The number of H+ relative to e- transferred in the reaction is 1:1, and their coupling is presumably performed by heme a and nearby residues. To perform this function, different parts of the protein need to cooperate with each other spontaneously and sequentially. It is the purpose of this article to describe the structural details on the coupling on the basis of the vibrational spectra of certain specified residues and chromophores involved in the reaction. Recent developments in time-resolved IR and Raman technology concomitant with protein manipulation methods have yielded profound insights into such structural changes. In particular, the new IR techniques that yielded the breakthrough are reviewed and assessed in detail. This article is part of a Special Issue entitled: Vibrational spectroscopies and bioenergetic systems. PMID- 25135481 TI - Neuromyelitis optica spectrum disorders without and with autoimmune diseases. AB - BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) can coexist with non organ-specific or organ-specific autoimmune diseases. The aim of this study was to investigate and compare the features between NMOSD without and with autoimmune diseases, and NMOSD with non-organ-specific and organ-specific autoimmune diseases. METHODS: One hundred and fifty five NMOSD patients without autoimmune diseases (n = 115) and with autoimmune diseases (n = 40) were enrolled. NMOSD with autoimmune diseases were divided by organ-specific autoimmune diseases. The clinical, laboratory and magnetic resonance imaging features between two groups were assessed. RESULTS: Motor deficit was less frequent in NMOSD patients with non-organ-specific autoimmune diseases (p = 0.024). Cerebrospinal fluid white blood cell and protein, serum C-reactive protein and immunoglobulin G were lower in NMOSD patients without autoimmune diseases, while several autoantibodies seropositivity and thyroid indexes were significantly higher in NMOSD patients with autoimmune diseases (p < 0.05). No difference was found in other clinical and laboratory characteristics between different NMOSD subtypes (p > 0.05). NMOSD patients with autoimmune diseases had higher brain abnormalities than NMOSD without autoimmune diseases (p < 0.001). CONCLUSIONS: The characteristics between NMOSD without and with autoimmune diseases were similar. NMOSD with autoimmune diseases have high frequency of brain abnormalities. PMID- 25135482 TI - Hormone whodunit: clues for solving the case of intratumor androgen production. AB - One of the key mechanisms by which prostate cancer cells evade hormone therapy is through intratumor testosterone production. New evidence points toward androstenedione as a potential precursor of intratumor androgen production and furthers nomination of AKR1C3 as a therapeutic target in advanced disease. PMID- 25135483 TI - p38 MAPK in pancreatic cancer: finding a protective needle in the haystack. AB - Activated p38 MAPK alpha (pp38alpha) is a good prognostic marker in pancreatic ductal adenocarcinoma that could be used to personalize therapy. pp38alpha suppresses JNK-mediated proliferation, both in vitro and in vivo. These findings support the testing of combination therapies that include JNK targeting and/or suppressing negative regulators of pp38alpha. PMID- 25135484 TI - Matching wits with melanoma brain metastases: from biology to therapeutics. AB - Melanoma brain metastases (MBM) present a significant clinical challenge. Molecular profiling of MBM is useful to identify molecular pathways, such as the PI3K pathway, that are specifically and differentially altered in MBM. Therapeutic studies should recruit patients with MBM and prospective tissue collection will lay the foundation for further advances. PMID- 25135486 TI - Relationship between Na+, K+-ATPase and NMDA receptor at central synapses. AB - Specific receptors for classical neurotransmitters and neuropeptides, as well as the Na(+), K(+)-ATPase, are all molecular entities inserted into synaptic region membranes and localized contiguously. Herein, available experimental evidence showing close interactions between the activity of the Na(+), K(+)-ATPase and the N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor was reviewed, supporting a functional link between these macromolecules. The Na(+), K(+)- ATPase and NMDA receptor are involved in ion movements through membranes. The former acts as an ion transporter, whereas the latter acts as an ion channel. The modulation of their activity plays a critical role in controlling neuronal function. Examples were taken from studies performed with specific agonists or antagonists of the NMDA receptor. Regarding the Na(+), K(+)-ATPase, its involvement was postulated after observing its inhibition by ouabain or related cardiac glycosides. Additionally, experimental conditions known to prevent normal Na(+), K(+)-ATPase (i. e., sodium pump functioning) led to similar valuable information. These findings indicate potential cross-talk between this enzyme and the NMDA receptor. The Na(+), K(+)-ATPase and NMDA play very important roles in the regulation of learning and memory in the hippocampus. The fact that important changes here described were recorded in the hippocampus indicate a different vulnerability of this area to toxicity induced by the Na(+), K(+)-ATPase inhibitor ouabain. Some interesting relationships include calcineurin actions, the participation of ERK or Src family kinases, and signaling cascades initiated by calcium. At present, many other examples of signaling related to the NMDA receptor cannot be correlated with Na+, K(+)-ATPase activity. It is desirable that the development of future research offer new clues for the relationship between Na(+), K(+)-ATPase and NMDA receptor activation. PMID- 25135485 TI - Transient extracellular application of gold nanostars increases hippocampal neuronal activity. AB - BACKGROUND: With the increased use of nanoparticles in biomedical applications there is a growing need to understand the effects that nanoparticles may have on cell function. Identifying these effects and understanding the mechanism through which nanoparticles interfere with the normal functioning of a cell is necessary for any therapeutic or diagnostic application. The aim of this study is to evaluate if gold nanoparticles can affect the normal function of neurons, namely their activity and coding properties. RESULTS: We synthesized star shaped gold nanoparticles of 180 nm average size. We applied the nanoparticles to acute mouse hippocampal slices while recording the action potentials from single neurons in the CA3 region. Our results show that CA3 hippocampal neurons increase their firing rate by 17% after the application of gold nanostars. The increase in excitability lasted for as much as 50 minutes after a transient 5 min application of the nanoparticles. Further analyses of the action potential shape and computational modeling suggest that nanoparticles block potassium channels responsible for the repolarization of the action potentials, thus allowing the cell to increase its firing rate. CONCLUSIONS: Our results show that gold nanoparticles can affect the coding properties of neurons by modifying their excitability. PMID- 25135489 TI - Staphylococcus aureus toxic shock syndrome toxin-1 (TSST-1) production and Lactobacillus species growth in a defined medium simulating vaginal secretions. AB - Lactobacillus species are commensal with the healthy vaginal environment and inhibit the growth of many pathogenic bacteria in the vaginal tract by a variety of mechanisms, such as the production of hydrogen peroxide, organic acids, and antimicrobial substances. Simulation of the vaginal environment is crucial for proper investigation of the effects of Lactobacillus species on pathogenic bacteria. In this study, we modified a medium used to simulate vaginal secretions to improve the growth of toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus clinical strains and Lactobacillus species so that interactions between these bacteria may be examined. A medium consisting of basal salts, vitamins, albumin, glycogen, mucin, urea, sodium bicarbonate, polyoxyethylene sorbitan monolaurate, and amino acids supported the growth of S. aureus and the production of TSST-1 as determined by Western analysis. Improved growth of the Lactobacillus species was seen when this same medium was supplemented with manganese chloride, sodium acetate, and an increase in glucose concentration. However, growth of S. aureus in the supplemented medium resulted in reduced levels of TSST-1. Production of TSST-1 was not detected in a medium routinely used for the growth of Lactobacillus species although S. aureus growth was not inhibited. The development of an improved genital tract secretion medium provides a more authentic environment in which to study the interactions of Lactobacillus species and vaginal pathogens, such as S. aureus. PMID- 25135488 TI - Rapid 96-well plates DNA extraction and sequencing procedures to identify genome wide transposon insertion sites in a difficult to lyse bacterium: Lactobacillus casei. AB - Random transposon mutagenesis followed by adequate screening methods is an unavoidable procedure to characterize genetics of bacterial adaptation to environmental changes. We have recently constructed a mutant library of Lactobacillus casei and we aimed to fully annotate it. However, we have observed that, for L. casei which is a difficult to lyse bacterium, methods used to identify the transposon insertion site in a few mutants (transposon rescue by restriction and recircularization or PCR-based methods) were not transposable for a larger number because they are too time-consuming and sometimes not reliable. Here, we describe a method for large-scale and reliable identification of transposon insertion sites in a L. casei mutant library of 9250 mutants. DNA extraction procedure based on silica membranes in 96-column format was optimized to obtain genomic DNA from a large number of mutants. Then reliable direct genomic sequencing was improved to fit the obtained genomic DNA extracts. Using this procedure, readable and identifiable sequences were obtained for 87% of the L. casei mutants. This method extends the applications of a library of this type, reduces the number of insertions needed to be screened, and allows selection of specific mutants from an arrayed and stored mutant library. This method is applicable to any already existing mutant library (obtained by transposon or insertional mutagenesis) and could be useful for other bacterial species, especially for highly lysis-resistant bacteria species such as lactic acid bacteria. PMID- 25135487 TI - Efficacy of antibiotic therapy for peritoneal dialysis-associated peritonitis: a proportional meta-analysis. AB - BACKGROUND: The choice of antimicrobials for initial treatment of peritoneal dialysis (PD)-related peritonitis is crucial for a favorable outcome. There is no consensus about the best therapy; few prospective controlled studies have been published, and the only published systematic reviews did not report superiority of any class of antimicrobials. The objective of this review was to analyze the results of PD peritonitis treatment in adult patients by employing a new methodology, the proportional meta-analysis. METHODS: A review of the literature was conducted. There was no language restriction. Studies were obtained from MEDLINE, EMBASE, and LILACS. The inclusion criteria were: (a) case series and RCTs with the number of reported patients in each study greater than five, (b) use of any antibiotic therapy for initial treatment (e.g., cefazolin plus gentamicin or vancomycin plus gentamicin), for Gram-positive (e.g., vancomycin or a first generation cephalosporin), or for Gram-negative rods (e.g., gentamicin, ceftazidime, and fluoroquinolone), (c) patients with PD-related peritonitis, and (d) studies specifying the rates of resolution. A proportional meta-analysis was performed on outcomes using a random-effects model, and the pooled resolution rates were calculated. RESULTS: A total of 64 studies (32 for initial treatment and negative culture, 28 reporting treatment for Gram-positive rods and 24 reporting treatment for Gram-negative rods) and 21 RCTs met all inclusion criteria (14 for initial treatment and negative culture, 8 reporting treatment for Gram-positive rods and 8 reporting treatment for Gram-negative rods). The pooled resolution rate of ceftazidime plus glycopeptide as initial treatment (pooled proportion = 86% [95% CI 0.82-0.89]) was significantly higher than first generation cephalosporin plus aminoglycosides (pooled proportion = 66% [95% CI 0.57-0.75]) and significantly higher than glycopeptides plus aminoglycosides (pooled proportion = 75% [95% CI 0.69-0.80]. Other comparisons of regimens used for either initial treatment, treatment for Gram-positive rods or Gram-negative rods did not show statistically significant differences. CONCLUSION: We showed that the association of a glycopeptide plus ceftazidime is superior to other regimens for initial treatment of PD peritonitis. This result should be carefully analyzed and does not exclude the necessity of monitoring the local microbiologic profile in each dialysis center to choice the initial therapeutic protocol. PMID- 25135490 TI - Non-Structural protein 1 (NS1) gene of Canine Parvovirus-2 regresses chemically induced skin tumors in Wistar rats. AB - The Non-Structural protein 1 of Canine Parvovirus-2 (CPV2.NS1) plays a major role in viral cytotoxicity and pathogenicity. CPV2.NS1 has been proven to cause apoptosis in HeLa cells in vitro in our laboratory. Here we report that CPV2.NS1 has no toxic side effects on healthy cells but regresses skin tumors in Wistar rats. Histopathological examination of tumor tissue from CPV2.NS1 treated group revealed infiltration of mononuclear and polymorphonuclear cells with increased extra cellular matrix, indicating signs of regression. Tumor regression was also evidenced by significant decrease in mitotic index, AgNOR count and PCNA index, and increase in TUNEL positive apoptotic cells in CPV2.NS1 treated group. Further, CPV2.NS1 induced anti-tumor immune response through significant increase in CD8(+) and NK cell population in CPV2.NS1 treated group. These findings suggest that CPV2.NS1 can be a possible therapeutic candidate as an alternative to chemotherapy for the treatment of cancer. PMID- 25135492 TI - Immunogenicity of recombinant BCGs expressing predicted antigenic epitopes of bovine viral diarrhea virus E2 gene. AB - To develop a vaccine to prevent diseases caused by Mycobacterium tuberculosis and bovine viral diarrhea virus (BVDV) simultaneously, recombinant Bacillus Calmette Guerin (rBCG) vaccines expressing different regions of the BVDV E2 gene were constructed. Using DNASTAR 6.0 software, potential antigenic epitopes were predicted, and six regions were chosen to generate recombinant plasmids with the pMV361 vector (pMV361-E2-1, pMV361-E2-2, pMV361-E2-3, pMV361-E2-4, pMV361-E2-5 and pMV361-E2-6, respectively). The recombinant plasmids were transformed into BCG, and protein expression was thermally induced at 45 degrees C. Mice were immunized with 5 * 10(6) CFU/200 uL of each rBCG strain. Compared with other groups, BVDV E2 specific antibody titers were higher in mice immunized with rBCG E2-6. Ratios and numbers of CD4+, CD8+ and IL-12 expressing spleen lymphocytes of the rBCG-E2-6 group also were higher than those of other groups. Thus, the rBCG E2-6 vaccine showed the highest immunogenicity of all groups based on the humoral and cellular responses to vaccination. PMID- 25135491 TI - Effects of salinomycin and Bacillus subtilis on growth performance and immune responses in broiler chickens. AB - The present study was undertaken to compare the effect of salinomycin and Bacillus subtilis on growth performance, serum antibody levels against Clostridium spp. and Eimeria spp., and cytokine mRNA expression levels in broiler chickens raised in the used litter. Broiler chickens fed a diet containing salinomycin showed lower (P < 0.05) body weights compared with the control diet fed counterparts. Serum nitric oxide levels were significantly (P < 0.05) elevated in chickens fed the B. subtilis-enriched diet compared with those on either the salinomycin-fed or control diet-fed chickens. None of the dietary treatments affected (P > 0.05) serum antibody levels against Clostridium perfringens toxins. Both salinomycin and B.subtilis significantly lowered (P < 0.05) the serum levels of Eimeria-specific antibodies compared with the control group. Salinomycin, but not B. subtilis, significantly modulated (P < 0.05) the expression of cytokines encoding interferon-gamma (IFN-gamma), interleukin10 (IL 10) and tumor necrosis factor superfamily 15 (TNFSF15) compared with the control group. In conclusion, dietary salinomycin and B. subtilis affected serum anticoccidial antibody and intestinal cytokine expression, but failed to improve growth performance in broiler chickens. Further study is warranted to investigate the mode of action of salinomycin on host immune response and growth performance in broiler chickens. PMID- 25135494 TI - Fusarium oxysporum induces the production of proteins and volatile organic compounds by Trichoderma harzianum T-E5. AB - Trichoderma species have been used widely as biocontrol agents for the suppression of soil-borne pathogens. However, some antagonistic mechanisms of Trichoderma are not well characterized. In this study, a series of laboratory experiments were designed to characterize the importance of mycoparasitism, exoenzymes, and volatile organic compounds (VOCs) by Trichoderma harzianum T-E5 for the control of Fusarium oxysporum f. sp. cucumerinum (FOC). We further tested whether these mechanisms were inducible and upregulated in presence of FOC. The results were as follows: T-E5 heavily parasitized FOC by coiling and twisting the entire mycelium of the pathogen in dual cultures. T-E5 growing medium conditioned with deactivated FOC (T2) showed more proteins and higher cell wall-degrading enzyme activities than T1, suggesting that FOC could induce the upregulation of exoenzymes. The presence of deactivated FOC (T2') also resulted in the upregulation of VOCs that five and eight different types T-E5-derived VOCs were identified from T1' and T2', respectively. Further, the excreted VOCs in T2' showed significantly higher antifungal activities against FOC than T1'. In conclusion, mycoparasitism of T-E5 against FOC involved mycelium contact and the production of complex extracellular substances. Together, these data provide clues to help further clarify the interactions between these fungi. PMID- 25135495 TI - Infectious diseases in Poland in 2012. AB - AIM: The aim of the study is to assess the epidemiological situation for infectious and parasitic diseases in Poland in 2012. MATERIALS AND METHODS: The main source of data for this study are statistical overviews contained in the annual bulletins "Infectious Diseases in Poland in 2012" and "Immunizations in Poland in 2012" (NIPH-NIH, Warsaw 2013) and data contained in the articles presented in this issue of Przeglad Epidemiologiczny. Information on deaths due to infectious and parasitic diseases registered in Poland in 2012 and earlier years is based on the data of the Department for Demographic Research of Central Statistical Office. RESULTS: Upper respiratory tract infection classified as "influenza and influenza-like illness" were reported in 2012 in a total number of 1 460 037 cases. In comparison with 2011, it was an 26.2% increase of incidence, and as compared to the median of 2006-2010 of 286.1%. In 2012, with still the clear predominance of salmonellosis among intestinal bacterial infections, downward trend in the incidence of intestinal infections of this etiology persisted. In 2012 reported number of intestinal infections caused by Salmonella was, 8 267 (21.5/100 000), which represents incidence decrease of 4.5%. Foodborne infections of viral etiology were reported in 39462 cases (102.4/100 000). Most frequent were caused by rotaviruses - 23 692 (61.5/100 000). In 2012, there were 4 684 reported cases of pertussis (12.2/100 000), which means an increased incidence compared with the previous year by 180%. In 2012, there was an increase in the number of cases of mumps by 7.5% (from 2 585 to 2 779 cases), and of rubella by 46.0%, but compared to the median of the years 2006 to 2010 it was a decrease of 52.9%. In 2012, there was not any case of congenital rubella. Number of measles cases was 70 (0.18/100 000). In 2012, there was an increase in the number of cases of invasive disease caused by H. influenzae from 31 in 2011 to 36 in 2012. Number of infections caused by Streptococcus pneumoniae remained in 2012 as compared to 2011, on almost the same level: 436 in 2012 and 430 in 2011. However, there was a 36% increase in the number of sepsis cases caused by this organism. The incidence of tuberculosis in total (all forms of TB) in 2012 decreased compared to the previous year from 22.0 to 19.6 /100000, and pulmonary tuberculosis from 20.5 to 18.2. In 2012, were reported 1 093 cases of HIV infections (2.84/100 000), compared with the previous year, it was a fall in incidence of 2.4%. 21 cases of malaria occurred in people, who infection acquired abroad in malaria endemic areas. In 2012, there were no cases of diphtheria, poliomyelitis, rabies and viral haemorrhagic fevers outside of dengue, of which 5 cases of infections acquired in endemic areas were reported to National Sanitary Inspection. Total number of people who died in Poland in 2012 due to infectious and parasitic diseases, was 2 774. The share of deaths from these causes in the total number of deaths was 0.72%, and the mortality rate - 7.2/100 000. Out of all those deaths 41.1% were due to sepsis. PMID- 25135493 TI - Identification of two dominant linear epitopes on the GP3 protein of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). AB - Glycosylated protein 3 (GP3) of PRRSV is variable between different PRRSV strains, so it is helpful for subtype classifying by using distinct epitopes. In this study, two dominant linear GP3 epitopes that were recognized by highly dilute serum in an enzyme-linked immunosorbent assay (ELISA) were identified. Sequence alignments of 36 North American (NA) PRRSV isolates revealed that the epitope H(87)DELGFMV(94) is well conserved, whereas the epitope T(59)RQAAAEILE(68) differs in other low-virulence NA-type strains, which have at least one amino acid mutation in this region. A mutational analysis revealed that none of these mutations could be recognized by the purified antibodies directed against the corresponding epitope, indicating that the genetic variations altered the antigenicity of the antigenic region. Using ELISA, we also found that antibodies directed against the two epitopes were present in more than 45 of 50 HP-PRRS-positive pig sera, suggesting that their antigenicity is excellent in vivo. PMID- 25135496 TI - Measles in Poland in 2012. AB - BACKGROUND: In 1998 Poland, along with all other Member States in the WHO European Region, implemented Measles Elimination Program coordinated by WHO. It requires achieving and maintaining very high vaccine coverage (>95%), recording all cases and suspected cases of measles, and laboratory testing of all suspected measles cases in the WHO Reference Laboratory. In Poland it is a Laboratory of Department of Virology, NIPH-NIH. AIM: To assess epidemiological situation of measles in Poland in 2012, including vaccination coverage in Polish population, and Measles Elimination Program implementation status. METHODS: The descriptive analysis was based on data retrieved from routine mandatory surveillance system and published in the annual bulletins "Infectious diseases and poisonings in Poland in 2012" and "Vaccinations in Poland in 2012", and measles case-based reports from 2012 sent to the Department of Epidemiology NIPH-NIH by Sanitary Epidemiological Stations. RESULTS: In total, there were 70 measles cases registered in Poland in 2012 (incidence 0.18 per 100 000). The highest incidence rate was observed among infants (2.08 per 100 000) and children aged 1 year (2.47 per 100 000). In 2012, 37 cases (52,9%) were hospitalized due to measles. No deaths from measles were reported. Vaccination coverage of children and youth aged 2-11 years ranged from 83.6% do 99.6% (primary vaccination in children born in 2011-2006) and from 76.6% do 96.7% (booster dose in children born in 2003 2001). Performance of the surveillance system was insufficient with only 127 measles-compatible cases reported in 2012 (33% of expected reports). Fifty cases (71%) were confirmed by IgM ELISA test. SUMMARY AND CONCLUSIONS: The epidemiological situation of measles deteriorated in 2012 in comparison to proceding year. The results indicate a need to further promote Measles Elimination Program in Poland, maintain the high immunisation coverage and improve measles surveillance system. PMID- 25135498 TI - Rubella in Poland in 2012. AB - BACKGROUND: In 2004, Poland has adopted the WHO goal of rubella elimination and congenital rubella syndrome prevention. Participation in the rubella elimination program requires clinical diagnosis of rubella to be confirmed with laboratory test. In Poland, until 2003, national vaccination recommendation included a dose of rubella vaccine only for girls aged 13 years. Among men, the incidence of measles remained high creating a risk of infection of non-immune pregnant women which may lead to the development of congenital rubella syndrome in the child. AIM: To assess epidemiological situation of rubella in Poland in 2012, including vaccination coverage in Polish population. METHODS: The descriptive analysis was based on data retrieved from routine mandatory surveillance system and published in the annual bulletins "Infectious diseases and poisonings in Poland in 2012" and "Vaccinations in Poland in 2012". RESULTS: In 2012, there was a significant increase in the number of cases of rubella - 6 263 cases (in 2011, 4 290 cases) - and the increase in incidence (from 11.1 per 100 thousand. 16.3). The highest incidence rate, regardless of gender and the environment, was observed among adolescents aged 15-19 years (118.0 per 100 000). As in 2011, the incidence of rubella in boys and men was higher than the incidence in girls and women (25.6 versus 7.5). In 2012, no cases of congenital rubella syndrome were registered. SUMMARY AND CONCLUSIONS: The proportion of laboratory tests confirming/excluding rubella infection is still very low in Poland. In 2012, only 0.2% of rubella cases were laboratory confirmed. PMID- 25135497 TI - Mumps in Poland in 2012. AB - BACKGROUND: Vaccination against mumps, introduced initially as recommended, from 2003 is mandatory in Poland and given as two dose scheme with MMR vaccine (mumps, measles, and rubella). Despite observed decline in mumps incidence for over a decade which is a result of conducted vaccinations, mumps is still a common childhood disease in Poland. AIM: To assess epidemiological situation of mumps in Poland in 2012, including vaccination coverage in Polish population, in comparison to previous years. METHODS: The descriptive analysis was based on data retrieved from routine mandatory surveillance system and published in the annual bulletins "Infectious diseases and poisonings in Poland in 2012" and "Vaccinations in Poland in 2012" (Czarkowski MP i in., Warszawa 2013, NIZP-PZH i GIS). Mumps cases were classified according to the criteria of surveillance case definition implemented in the European Union (Commission Decision of 28 April 2008 amending Decision 2002/253/EC). National Immunisation Programme for year 2012 was also used. RESULTS: In total, there were 2779 mumps cases registered in Poland in 2012. Incidence of mumps was 7.2 per 100 000 and it was higher by 7.5% in comparison with 2011 and lower by 19.4% in comparison to median for the years 2006-2010. The highest incidence rate was observed among children aged 5 years (71.8 per 100 000). Incidence in women (5.9) was lower than in men (8.6). In 2012, 25 people were hospitalized due to mumps. Vaccination coverage of children aged 3 years in Poland in 2012 was 97.9%. CONCLUSIONS: Systematic execution of mumps vaccination in accordance with the National Immunisation Programme resulted in a significant decrease in the number of registered cases. Due to the high vaccination coverage further decline in the number of cases is expected. PMID- 25135499 TI - Chickenpox in Poland in 2012. AB - BACKGROUND: A number of chickenpox cases, occurring especially in children, indicates the rationale for the use of chickenpox vaccinations. In Poland since 2002, chickenpox vaccination is included in the National Immunisation Programme as recommended. AIM: To assess epidemiological situation of chickenpox in Poland in 2012 in comparison to previous years. METHODS: The descriptive analysis was based on data retrieved from routine mandatory surveillance system and published in the annual bulletins "Infectious diseases and poisonings in Poland in 2012" and "Vaccinations in Poland in 2012" (Czarkowski MP i in., Warszawa 2013, NIZP PZH i GIS). National Immunisation Programme for year 2012 was also used. RESULTS: In 2012, 208 276 cases of chickenpox were registered in Poland. The highest number of cases was reported in Slaskie voivodeship, the lowest in Podlaskie voivodeship. Mumps incidence was 540.5 per 100 000 and was higher than in 2011 (448.7). The highest incidence was recorded in children aged 4 years (7 611.5 per 100 000). The chickenpox incidence among men (570.7) was higher than among women (512.2). The incidence among rural residents (553.9) was higher than among urban residents (531.8). Number of cases hospitalized due to mumps was 1 361. Number of people vaccinated against chickenpox was 56 213. SUMMARY: In 2012, there was an increase in the incidence of smallpox in Poland. This trend is continuing since 2004, which can be partly explained by improved surveillance of the disease. PMID- 25135500 TI - Pertussis in Poland in 2012. AB - INTRODUCTION: The epidemiological situation of pertussis in recent years has changed dramatically. There is a high percentage of cases of pertussis among adolescents and adults. Infected adults can be a source of infection for non immune individuals such as infants. The best strategy to prevent illness remains the implementation of vaccination in accordance with the applicable calendar. THE AIM OF THE STUDY: To assess the epidemiological situation of pertussis in Poland in 2012 in comparison to previous years and evaluation of vaccine coverage of children. MATERIALS AND METHODS: Assessment of the epidemiology of pertussis in Poland was based on analysis of individual reports of suspected cases of pertussis sent to the NIPH-NIH by the Regional Sanitary-Epidemiological Stations, data from the bulletin "Infectious diseases and poisonings in Poland in 2012" and bulletin "Immunizations in Poland in 2012 "(MP Czarkowski et al., Warsaw 2013, NIPH-NIH, GIS). RESULTS: In 2012, number of registered cases of whooping cough was 4 684. The incidence was 12.2 per 100 000 children which was three times as many as in the previous year (4.3) The majority of cases was among adolescents aged 10-14 years and above 15 years of age (77%). Number of hospitalized persons was 1503, (32%) of reported cases. In 2012, there were no deaths from whooping cough. SUMMARY AND CONCLUSIONS: Observed in 2012, the epidemic increase in the incidence of pertussis in comparison with previous years, indicates the circulation of bacteria in the environment and the high sensitivity of the population to infection. PMID- 25135501 TI - Scarlet fever in Poland in 2012. AB - OBJECTIVE: Assessment of the epidemiological situation of scarlet fever in Poland in 2012. MATERIALS AND METHODS: The evaluation was performed by analysing surveillance data published in the bulletin, "Infectious diseases and poisonings in Poland in 2012" (Warsaw 2013, NIPH-NIH, CSI) and also in bulletins from previous years, and unpublished data collected under Statistical survey program of official statistics. RESULTS: In the last 15-20 years in Poland has been observed more than 2-fold lengthening of scarlet fever epidemic cycle, slowdown in the decline and slower growth rate in epidemic curve and decrease in average annual incidence. In 2012, in the country a total of 25 421 cases were registered and incidence was 66.0 per 100 000 population (in voivodeships: from 25.8 in lodzkie to 114.2 in pomorskie). The highest incidence was notified in 5-year-old (1094.7) and 6-year-old children (877.3), however, the incidence among children and young people up to 15 years accounted for 95.6% of all cases. The incidence of men (74.8) was higher by almost 30% than the incidence of women (57.6). The incidence was higher in urban areas than in rural areas and was 72.7 (in rural area 55.7). 0.9% of patients were hospitalized. No deaths related to the disease were reported. SUMMARY: Distinct changes in the epidemiological situation of scarlet fever in recent decades are related to, i.a., aging of the Polish population and decline in the number of children, group particularly vulnerable to infection. In order to improve accuracy of surveillance data, it is recommended significantly increase percentage of cases in which clinical diagnosis will be confirmed by the result of bacteriological examination. PMID- 25135502 TI - Meningitis and encephalitis in Poland in 2012. AB - AIM OF THE STUDY: The aim of this study was to assess the epidemiology of meningitis and/or encephalitis in Poland in 2012. INTRODUCTION: About 2 500-3 000 cases of meningitis and/or encephalitis of viral or bacterial etiology are recorded in Poland every year. MATERIALS AND METHODS: Assessment of the epidemiological situation of meningitis and/or encephalitis in Poland in 2012, was based on the results of analysis of epidemiological reports sent to the NIZP PZH by the Regional Sanitary-Epidemiological Stations published in the annual bulletin "Infectious diseases and poisonings in Poland in 2012" and "Preventive immunizations in Poland in 2012" (Czarkowski MP. et al., Warsaw, 2013, NIZP-PZH, GIS). RESULTS: In 2012 in Poland 3 088 cases of meningitis and/or encephalitis were recorded. More than 50% of these were viral infections. SUMMARY AND CONCLUSIONS: The epidemiological situation of inflammatory meningitis and encephalitis in Poland in 2012 compared to 2011 did not change significantly. PMID- 25135503 TI - Legionellosis in Poland in 2012. AB - OBJECTIVE: The objective of the article is to assess the epidemiological situation of legionellosis in Poland in 2012 in comparison to the preceding years. MATERIAL AND METHODS: The analysis of epidemiological situation was based on the data published in the annual bulletin: "Infectious diseases and poisonings in Poland in 2012" and its prior versions as well as the legionellosis case reports sent to the Department of Epidemiology of NIPH-NIH. RESULTS: In Poland, all cases of legionellosis, including Legionnaires' disease - a form of disease accompanied by pneumonia and mild, influenza-like form of infection - Pontiac fever are routinely reported to the surveillance. In 2012, a total of 10 legionellosis cases were reported (8 cases of Legionnaires' disease and 2 cases of Pontiac fever); the incidence was 0.026 per 100 000 population which compared to the previous year and median incidence for 2006-2010 was 45% and 65% lower, respectively. The infections were reported in 6 provinces. The incidence in males (0.03 per 100 000) was slightly higher compared to females (0.02). No legionellosis outbreaks were registered - all infections were of sporadic nature. All cases were hospitalized. The sanitary inspection reported two fatal cases over the age of 60. Of these infections, seven were developed in the country, including one hospital- and one sanatorium-acquired infection. Two infections were associated with travels abroad (one to Spain and one to Egypt) and one infection occurred in driver while transporting the goods to the Netherlands. CONCLUSIONS: In 2012, no changes of fundamental features of legionellosis epidemiological situation in Poland were observed. It is recommended to enhance the surveillance for legionellosis, with emphasis on conducting environmental investigation in areas where infections have occurred. PMID- 25135504 TI - Shigellosis in Poland in 2012. AB - BACKGROUND: Shigellosis according to European Centre for Disease Control (ECDC) Report is registered in all countries of the European Union (EU) and of the European Free Trade Association (EFTA) with exception of Italy and Luxemburg. The incidence rate in Poland below 0.1/100 000 of population is the lowest among the EU/EFTA countries. AIM: To assess epidemiological situation of shigellosis in Poland in 2012 in comparison to preceding years. MATERIALS AND METHODS: An assessment of the epidemiological situation of shigellosis was based on the results from an analysis of the yearly annual bulletins: "Infectious diseases and poisonings in Poland in 2012", reports from bacteriological laboratories and reports from individual cases and epidemiological investigations of outbreaks linked to shigellosis, sent by Sanitary-Epidemiological Stations to the Department of Epidemiology at NIZP-PZH. RESULTS: In 2012 the tendency that the number of registered cases of shigellosis was lower than in the former years continued - only 13 confirmed cases of shigellosis were registered (incidence rate 0.03 per 100 000 inhabitantsbut in the previous year the 18 cases ( incidence rate 0.05). Cases were registered only by 6 provinces, most of the cases by the Lodz province - 4. All together 5 persons nearly 40% were infected in travel to the foreign countries. According to data from laboratories of Sanitary-Epidemiological Stations, Shigella was detected only 4 convalescents and 2 carriers. All cases of shigellosis registered in 2012, were confirmed by a hospital laboratory or a private laboratory. CONCLUSIONS: In our opinion the above mentioned data concerning the cases of shigellosis in Poland in 2012 are not reflecting the true epidemiological situation of shigellosis in Poland. The sanitary situation was changing nearly every year for better than in former years but the surveillance of dysentery require more active epidemiological measures. PMID- 25135505 TI - Foodborne infections and intoxications in Poland in 2012. AB - AIM: The purpose of the study is to assess the epidemiological situation of foodborne infections and intoxications in Poland in 2012. MATERIALS AND METHODS: The evaluation was based on analysis of information from reports of epidemiological investigations in foodborne outbreaks, submitted by the sanitary epidemiological stations to the Department of Epidemiology, NIZP-PZH annual bulletins (Czarkowski MP et al. "Infectious diseases and poisonings in Poland", 2006-2012. Warsaw, NIPH-NIH and CSI). RESULTS: In Poland in 2012 there was observed decrease in the number of infections intoxications both of bacterial and viral origin. It was recorded only one case of trichinellosis. There were reported 491 outbreaks of foodborne poisonings or infections included 5 774 people, among them 718 children 1-14 years old. Out of them 1 364 people were hospitalized. Unlike last year, the predominant etiological agent in those outbreaks were zoonotic Salmonella serotypes which caused 38.1% outbreaks and 26.7% outbreak cases. The viruses have caused 27.1% of outbreaks and 36.2% of cases. In 23.8% of outbreaks etiological agent has not been established. Most often the settings of an outbreak was a private household - 236 outbreaks and a hospital (84 outbreaks). As in previous years, the most common vehicle of infection were foods prepared with milk and eggs -11.8% of outbreaks and egg dishes - 9.0%. In 57.6% of oubreaks vehicle of infection has not been established. Among outbreaks reported in 2012, there were 4 which involved more than 100 people. In 163 outbreaks of food items had been tested and in 33% of them the results were positive. CONCLUSIONS: The increasing negative results of bacteriological examinations of food items, suggested necessity to start testing food contamination with viruses. PMID- 25135506 TI - Yersiniosis in Poland in 2012. AB - AIM: The aim of this study is to assess the epidemiology of yersiniosis in Poland in 2012 compared to previous years. MATERIAL AND METHODS: We reviewed surveillance data published in the annual bulletin "Infectious diseases and poisonings in Poland" from 2007 to 2012 (MP Czarkowski et al., NIH and GIS) and individual yersiniosis case reports from 2012 sent by the Sanitary Epidemiological Stations. Additionally, we used data from the Department of Demographic Surveys in Central Statistical Office. RESULTS: In Poland in 2012 a total of 231 yersiniosis cases were reported including 201 cases of intestinal and 30 cases of extraintestinal yersiniosis; 61.9% of patients were hospitalized. The incidence rate was 0.6 per 100 000 inhabitants. No deaths related to the disease were reported. Intestinal yersiniosis was manifested mostly by following symptoms: diarrhoea (87%), fever (76%), abdominal pain (47%) and vomiting (31%). The most affected group in intestinal infections were children younger than 4 years - 145 cases (72% of all cases). Extraintestinal form of infection was more common than in 2011 (19 cases) and usually involved symptoms from the osteoarticular system, noted in 90% of patients. Similarly to the previous year (2011) most cases of yersiniosis were reported from Mazowieckie province (103), no case has been reported from Swietokrzyskie province. Serological types of Yersinia enterocolitica were identified in 120 cases (52%): serotype O3 (96.7%), O8 (2.5%) and O9 (<1%). There were two household outbreaks. In comparison to previous years the total number of cases caused by serotype O8 has significantly decreased - from 55 cases in 2011 to 3 cases in 2012. CONCLUSIONS: A large percentage (48%) of unknown Yersinia serotypes is a consequence, that physicians do not always request serotyping in routine diagnostics. Reporting cases of extraintestinal yersiniosis from only few provinces may suggest that the real number of infections remains underreported. PMID- 25135507 TI - Campylobacteriosis in Poland in 2012. AB - AIM: The aim of this paper is to evaluate epidemiological situation of campylobacteriosis in Poland in 2012, compared to the situation in previous years. MATERIALS AND METHODS: The evaluation was based on analysis of data from the annual bulletin "Infectious diseases and poisonings in Poland" 2011-2012 (MP Czarkowski et al., NIZP-PZH and Chief Sanitary Inspectorate-GIS), information from the forms of individual cases reports from the epidemiological investigations in outbreaks of campylobacteriosis, submitted by the sanitary epidemiological stations to the Department of Epidemiology and data from the Department of Demographic Studies of the Central Statistical Office. Cases were classified according to a surveillance case definition. RESULTS: In 2012, 431 cases of campylobacteriosis were registered in Poland, which was 30% more than in 2011. The incidence was 1.12/100 000. All reported cases were classified. No deaths were recorded. More than 84% of cases of campylobacteriosis occurred in four provinces - Warminsko-Mazurskie (35%), Slaskie (22%), Mazowieckie (14%) and the Malopolskie (14%). The highest incidence was observed in the Warminsko Mazurskie- 6.47/100 000. As in previous years, the percentage of hospitalized cases was 57.5%. Campylobacter species was identified in more than 77% of patients, and it was found that 70% of the cases were caused by C. jejuni and about 7% by C. coli. As in previous years, the majority of cases (343, 79%) occurred in the age group 0-4. Five family outbreaks caused by Campylobacter were recorded in 2012. CONCLUSIONS: In Poland Campylobacteriosis is rarely diagnosed, confirmed and reported. Routine diagnosis of infection with Campylobacter sp. is performed only in the two provinces. PMID- 25135508 TI - Salmonellosis in Poland in 2012. AB - AIM: The purpose of the study was evaluation of epidemiological situation of salmonellosis in Poland in 2012 compared to the previous years. MATERIALS AND METHODS: The main source of data for this study are statistical overviews contained in the annual bulletins "Infectious Diseases in Poland in 2012" (NIZP PZH, GIS, Warsaw 2013), reports from investigations obtained from the sanitary epidemiological stations. Information on deaths due to infectious and parasitic diseases registered in Poland in 2012 and earlier years is based on the data from the Department for Demographic Research of Central Statistical Office. For the purpose of surveillance cases were classified according to the case definition. RESULTS: In Poland in 2012, it was reported a total of 8 444 cases of zoonotic salmonellosis including 8 267 cases of intestinal salmonellosis and 177 of extraintestinal one. The incidence was 21.9/100 000. The criteria for a confirmed case met more than 94% of cases. The number of reported cases was lower than in 2011, reflecting the continued downward trend in the number of cases of salmonellosis in Poland. A very high percentage (69.4%) hospitalizations of people infected with zoonotic Salmonella remains. In outbreaks proportion of hospitalizations accounted for one third of the cases. Predominated children under the age of 5 years. Seven people died of salmonellosis. In 2012, it was reported 181 outbreaks caused by Salmonella in which 1 511 people still. They were mostly small family outbreaks. The most common etiological agent of salmonellosis in Poland is S. enteritidis, but slightly increases the percentage cases, for which no serologic type was determined. In 2012 it stood at 14%. This proportion was highest in the Pomorskie province and amounted to 58%. CONCLUSIONS: Keeping up for more than 10 years in the percentage of salmonellosis hospitalization rate at 70%, indicates underreporting of the disease in the country and mostly detection of the cases requiring hospital treatment. Growing proportion of Salmonella that are not serotyped, reaching in some regions more than 30% indicates problems with laboratory diagnostics salmonellosis. PMID- 25135509 TI - Foodborne botulism in Poland in 2012. AB - OBJECTIVES: The main objective of this article is to assess the epidemiology of foodborne botulism in Poland in 2012 compared to previous years, using national surveillance data. MATERIALS AND METHODS: We reviewed surveillance data published in the annual bulletin "Infectious diseases and poisonings in Poland in 2012" and in previous publications, and botulism case reports for 2012 sent to the Department of Epidemiology NIPH-NIH by Sanitary-Epidemiological Stations. RESULTS: In 2012, a total of 22 foodborne botulism cases (including 9 laboratory confirmed cases) was reported, corresponding to the lowest annual incidence rate (0.06 per 100 000 population) since the introduction of botulism as mandatory notifiable disease. The highest incidence in the country was reported in Lubelskie (0.23) and Wielkopolskie (0.20). Incidence in rural areas (0.07 per 100 000 population) was slightly higher than the incidence in urban areas (0.05). Men had more than 2 times higher incidence than women; the highest incidence rate (0.20 per 100 000 population) was observed among men in the age group of 30-39 years. Most cases were associated with consumption of different types of commercially canned meat. Commercially canned fish was also a common vehicle. All cases were hospitalized. One death related to the disease was reported. CONCLUSIONS: In 2012, in Poland a downward trend in the incidence of foodborne botulism was maintained. From the point of view of national surveillance, it is necessary to increase the percentage of cases investigated with laboratory tests. PMID- 25135510 TI - Hepatitis A in Poland in 2012. AB - AIM: The aim of the article is evaluation of the epidemiological situation of hepatitis A in Poland in 2012. MATERIALS AND METHODS: Assessment of epidemiological situation of hepatitis A was based on results from analysis of the annual bulletins: "Infectious diseases and poisonings in Poland in 2012", "Vaccinations in Poland in 2012", reports from individual cases and epidemiological investigations of outbreaks linked to hepatitis A, sent by Epidemiological Departments in Sanitary Epidemiological Stations to the Department of Epidemiology at NIPH-NIH. RESULTS: In Poland, 71 cases of hepatitis A were registered in 2012. The incidence of 0.17/ per 100 000 inhabitants was slightly higher than previous year. The incidence of hepatitis A ranged from 0.08/100 000 in Lodzkie and Podlaskie to 0.35/100 000 in Slaskie. The incidence of hepatitis A in men and women was at an approximate level and amounted to 0.19 and 0.18/100 000 respectively. The peak of incidence was recorded during the summer and autumn-winter months. In 2012 imported cases constituted 52.1% of all cases of hepatitis A. There were five outbreaks involving of 11 registered cases in 2012. CONCLUSIONS: In 2012, there was a slight increase in the incidence of hepatitis A in compared with the previous year. However, apart from that there were no significant changes in the epidemiological situation of hepatitis A. In Poland there is still very low endemicity for hepatitis A. Decreased incidence and the small number of people vaccinated against hepatitis A facilitates the accumulation of a fairly numerous population of persons susceptible to infection which is connected with the possibility to increase the number of cases of hepatitis A. Despite the fact that the current epidemiological situation of hepatitis A in Poland is good, the disease still requires monitoring and analysis within the framework of epidemiological surveillance system. PMID- 25135511 TI - Hepatitis B in Poland in 2012. AB - OBJECTIVES: Evaluation of the epidemiological situation of hepatitis B in Poland in 2012 in comparison with previous years. MATERIAL AND METHODS: The evaluation was based on the results of analysis of individual case reports of acute hepatitis B recorded by the Sanitary-Epidemiological Stations and aggregate data of national surveillance published in annual bulletins "Infectious diseases and poisonings in Poland" for the years 2006-2012. RESULTS: In Poland, in 2012 a total of 1 583 cases of hepatitis B were reported, including 33 cases of dualinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The incidence was 4.11 per 100 000 inhabitants and compared to the preceding year its value did not change. The acute cases accounted for 4.9% of all hepatitis B cases, the incidence - 0.20 per 100 000 population. Compared to 2011, there was a further decline in both incidence and share of acute stage of infection in the total number of cases. The highest incidence of acute and chronic form of hepatitis B was reported in Opolskie (0.49 per 100 000) and Lodzkie provinces (8.62 per 100 thousand.), respectively. More frequently men and urban dwellers were ill. In the age group 0-14 years, which was entirely covered by universal vaccination of infants, no acute cases were found while the incidence of chronic hepatitis B in this age group was 0.14 per 100 000. Chronic hepatitis B was most frequently detected in people aged 40-44 years (incidence 7.13 per 100 000) and acute disease - in those aged 45-49 years (incidence 0.46 per 100 000). Medical procedures in healthcare settings were still the predominant route of infection (56% of all acute cases). Infections contracted via sexual contacts, household contact with an infected person and through injection drug use accounted together for 14% of all acute hepatitis B cases. In 2012, 11 and 41 persons died due to acute and chronic stage of hepatitis B, respectively. CONCLUSIONS: A clear downward trend of the incidence of acute hepatitis B with an unchanged mode of HBV transmission in Poland, indicates an improvement in compliance with recommended infection control procedures at all levels of medical care. The maintenance of the incidence of acute hepatitis B at a low level is possible due to the continuation of an universal vaccination program against HBV in combination with measures that stop the spread of infections. In view of persistent pattern of hepatitis B transmission in Poland in medical settings, it is advisable to recommend immunization not only to individuals at increased risk but also all previously unvaccinated persons. Simultaneously, activities leading to the improvement of detectability and the availability of the recommended treatment of chronic hepatitis B should be strengthened. PMID- 25135512 TI - Hepatitis C in Poland in 2012. AB - INTRODUCTION: In Poland, an estimated 2 000 HCV infections are reported annually, of which chronic stage of infections predominates (>95%). It is estimated that seroprevalence of anti-HCV and prevalence of active infections in the general population amount to ca 0.95% (more than 320 000 persons) and 0.6% (230 000 persons), respectively. The alarming finding is that approximately 90% of persons diagnosed with HCV infection are unaware of the condition and consequently hepatitis C virus may be transmitted to their contacts. OBJECTIVE: The objective of the present article is to determine the epidemiology of HCV infections in Poland in 2012 comparing to the preceding years. MATERIAL AND METHODS: The assessment of epidemiological situation of HCV infections in Poland was based on the analysis of aggregated data from the State Sanitary Inspection, published in "Infectious diseases and poisonings in Poland in 2012" (Czarkowski MP et al. "Infectious diseases and poisonings in Poland in 2012" Warsaw, NIPH-NIH and CSI). The data on mortality due to hepatitis C, which was obtained from the Demographic Surveys and Labour Market Department of Central Statistical Office, were also employed. RESULTS: In 2012, Poland reported 2 292 HCV infections, meeting 2005 definition (incidence 5.95), of which 1.4% were co-infections with HCV and HBV (33 cases). Compared to the data of 2011, the incidence was slightly lower (2 338; 6.07). Given 2009 definition, a total of 2 265 cases were reported (5.88), which constituted an increase of 3.5% compared to the data from the previous year (2 241; 5.82). Overall, 217 fatal cases due to hepatitis C were reported in 2012, of whom only 9 (4%) were due to acute stage of infection. CONCLUSIONS: Compared to the data from 2011, the epidemiological situation of hepatitis C in Poland has not changed significantly. The alarming fact is the increasing number of deaths due to hepatitis C. Probably, it suggests delayed diagnosis of HCV infections. Thus, it is a necessity to promote early diagnosis of HCV infections which can prevent life and health-threatening sequelae of hepatitis C. PMID- 25135513 TI - Tetanus in Poland in 2012. AB - INTRODUCTION: Despite of the small number of cases reported in Poland tetanus is a permanent risk to unvaccinated people. The severity of the disease is associated with high case fatality, especially among people in older age groups. THE PURPOSE OF THE STUDY: The aim of this paper is to present the data of epidemiological surveillance of tetanus in 2012. MATERIAL AND METHODS: Principal source of the data is bulletin: "Infectious diseases and poisonings in Poland in 2012, and individual reports of cases of tetanus sent to the Department of Epidemiology, NIPH -NIH. RESULTS: In 2012, there were reported 19 cases of tetanus. 6 cases occurred in men, and 13 women. 13 cases occurred in persons over 69 years of age and in those age groups 6 cases were fatal. The paper describes the geographical distribution and the month of infection, the nature of the wounds which were portals of infection and the duration of incubation period of the cases. SUMMARY AND CONCLUSIONS: Severity of tetanus, despite a small number of cases each year leads to several deaths, which could be prevented by vaccination. PMID- 25135514 TI - Lyme disease in Poland in 2012. AB - INTRODUCTION: In Poland registration of all cases of Lyme disease is conducted by the Epidemiological Unit of National Institute of Public Health - National Institute of Hygiene. Most cases of Lyme disease occur in the North- East region of Poland; however, it is important to note that the disease is no longer solely a problem of this region of Poland. OBJECTIVES: The aim of this work is to assess the epidemiological situation of Lyme disease in Poland in 2012 as compared to the situation in the previous years. MATERIALS ANDD METHODS: Assessment of the epidemiological situation of Lyme disease in Poland was made on the basis of an analysis of individual notifications of suspected Lyme disease submitted to NIZP NIH by the Provincial Sanitary- Epidemiological Stations; as well as data from "Infectious diseases and poisoning in Poland in 2012" bulletin, and "Vaccinations in Poland in 2012" bulletin (MP Czarkowski and Co, Warsaw 2013, NIPH-NIH, NCI). RESULTS: In 2012 there were 8 782 registered cases of Lyme disease and it is 4.3% higher than in the previous year. The overall incidence in the country amounted to 23.8 per 100 000 people. The highest incidence rate was recorded in Podlaskie province - 75.5 per 100 000 people. 2 063 people were hospitalized due to Lyme disease. SUMMARY AND CONCLUSIONS: In 2012 incidence rate of Lyme disease was gradually dropping down. The registered number of cases was reduced by 4.1% in comparison to the previous year. There is still a fairly low percentage of cases detected with diagnostic test called Western blot method. PMID- 25135515 TI - Echinococcosis and cysticercosis in Poland in 2012. AB - AIM: The aim of the study was to assess the epidemiological situation of echinococcosis and cysticercosis in 2012 as compared to previous years. MATERIALS AND METHODS: The assessment of the epidemiological situation was based on data contained in the individual reports on cases sent to the Department of Epidemiology NIPH-NIH by the Regional Sanitary- Epidemiological Stations and on the pooled data published in the annual bulletin "Infectious diseases and poisonings in Poland". RESULTS: In 2012, the total number of reported cases of echinococcosis in Poland was 28. This included: 11 undefined cases (39% of all cases), 7 alveolar echinococcosis cases (41% out of l7 cases in which the species of Echinococcus was recognized) and 10 cystic echinococcosis (59% of all defined cases). The total incidence of echinococcosis was 0.073/100 000. Cases were registered in 8 provinces. Most cases (9) and the highest incidence (0.620) was recorded in Warminsko-Mazurskie. Echinococcus infections were reported in people aged 15 to 82 years, mostly adults (mean age 49.2 years, median 54.0). Echinococcosis was more frequent among women (incidence 0.096) than among men (incidence 0.048). The incidence of echinococcosis in rural areas was higher than in the city (0.125 vs. 0.039). Cysticercosis, which occurs sporadically in Poland, was not reported in 2012. CONCLUSIONS: For the purposes of epidemiological surveillance it would be advisable to introduce the obligatory differentiation of alveococcosis and hydatidosis, as well as a case definition for cysticercosis. In order to reduce the risk of contracting tapeworm infections, it is advisable to intensify educational efforts. PMID- 25135516 TI - HIV and AIDS in Poland in 2012. AB - INTRODUCTION AND AIM: From 1985 until the end of 2013, 17 565 cases of HIV infection, 3 062 AIDS cases and 1 246 deaths due to AIDS were registered in Poland. In this paper we aim to analyze the epidemiological situation of newly diagnosed HIV infections and AIDS cases in Poland in 2012. MATERIALS AND METHODS: Descriptive analysis of newly detected HIV cases and incident AIDS cases was performed based on routine notifications by clinicians and laboratories. Data on the number of HIV tests from annual survey among laboratories were also used. RESULTS: In 2012 there were 1 093 HIV cases diagnosed in Poland (detection rate 2.84 per 100 000 population), including 27 non-Polish citizens. The detection rate remained comparable to 2011, but approximately 30% higher than in 2006-2010. The total number of AIDS cases was 155 (incidence 0.40 per 100 000) and 57 AIDS patients died (0.15 per 100 000). HIV infection is mainly detected among people aged 20-39 years (72.6%) and males (83.5%). As many as 70% of newly diagnosed infections with known route of transmission occurred among men who have sex with men (MSM). The number of infections in this group increased by 9% from 2011 and over 3 times compared to 2006-2010 average. The percentage of late presenters (defined by the time between HIV and AIDS diagnoses of less than 3 months) decreased in comparison with 2011 (7.9% of newly diagnosed HIV infections). CONCLUSIONS: HIV epidemic is still spreading among MSM in Poland. However, assessment of epidemiological situation is limited by the lack of data on the probable transmission route in a large percentage of reports of newly diagnosed HIV cases. PMID- 25135517 TI - Malaria in Poland in 2012. AB - OBJECTIVE: To describe the epidemiological situation of imported malaria in Poland in 2012 as compared with previous years. MATERIAL AND METHODS: Evaluation of malaria epidemiological situation in Poland in 2012, based on the results of the analysis of individual reports sent to the NIPH-NIH by the Sanitary Epidemiological Stations and aggregate data published in the annual bulletins "Infectious Diseases and Poisonings in Poland". Cases were registered according to the case definition approved in the EU countries. RESULTS: In 2012, a total of 21 malaria cases were registered in Poland, including one fatal case. All cases were imported from malaria-endemic countries: 52% from Africa and remaining cases from Asia. Overall, compared to 2011, 7 more cases were reported. Given a median for the years 2006-2010, the number remained at the same level. In one patient the recurrence of malaria falciparum was observed following the failure of treatment undertaken in Cameroon. Plasmodium species was determined in 18 cases (86%); including 10 (61%) caused by P. falciparum, 6 (33%) by P. vivax and one by P. malariae. One patient was diagnosed with mixed invasion. Infections were occurred most frequently during work-related trips (43%) or tourist trips (38%), in other cases the purpose of the journey was to visit the country of origin (14%) or its purpose remained unknown. Only four people took any chemoprophylaxis; in one case, a drug matched inappropriately to the destination was applied, the remaining three persons applied drugs contrary to the recommended drug regimen. CONCLUSIONS: The number of cases of imported malaria in Poland remained at a low level, similar to that observed in previous years. A large number of delayed diagnoses (more than half of the reported cases) and another case of fatal outcome in the course of malaria indicate still low awareness of malaria threat among both travelers and primary care physicians. PMID- 25135518 TI - Tuberculosis in Poland in 2012. AB - AIM OF THE STUDY: To evaluate the main features of TB epidemiology in 2012 in Poland and to compare with the corresponding EU data. METHODS: Analysis of case- based clinical and demographic data on TB patients from Central TB Register, of data submitted by laboratories on anti-TB drug susceptibility testing results in cases notified in 2012, data from National Institute of Public Health - National Institute of Hygiene on cases of tuberculosis as AIDS-defining disease, from Central Statistical Office on deaths from tuberculosis based on death certificates, data from ECDC report "Tuberculosis Surveillance in Europe, 2014 (situation in 2012). RESULTS: 7 542 TB cases were reported in Poland in 2012. The incidence rate was 19.6 cases per 100 000, with large variability between voivodships from 10.6 to 30.2. The mean annual decrease of TB incidence in 2008 2012 was 2.4%. 6 665 cases had no history of previous treatment; 17.3 per 100 000. The number of all notified pulmonary tuberculosis cases was 7 018; 18.2 per 100 000. The proportion of extrapulmonary tuberculosis among all registered cases was 6.9% (524 cases). In 2012, 36 patients had fibrous-cavernous pulmonary tuberculosis (0.5% of all cases of pulmonary tuberculosis). TB was diagnosed in 95 children (1.3% of all cases, incidence 1.6). The incidence of tuberculosis increased progressively with age to 34.8 among patients 65 years old and older. The mean age of new TB cases was 53.1 years. The incidence among men (27.4) was more than two times higher than among women (12.2). The incidence rate in rural population was lower than in urban; 20.2 vs. 18.6. Bacteriologically confirmed pulmonary cases (4870) constituted 69,4% of all pulmonary TB cases. The number of smear positive pulmonary TB cases was 2 778 (39.6% of all pulmonary cases). In 2012 in the all group of TB patients in Poland there were 276 (3.7%) of homeless and 1 905 (25.3%) of unemployed. There were 48 foreigners registered among all cases of tuberculosis in Poland (0.6%) and 243 cases registered among prisoners (rate 288.0). There were 31 patients with MDR-TB (0.7% of 4659 cases with known anti-TB DST results). TB was initial AIDS indicative disease in 26 cases. There were 640 deaths due to tuberculosis in 2011 (1.7 TB deaths per 100 000). Mortality among males - 2.7 - was four times higher than among females - 0.7. CONCLUSIONS: CONCLUSIONS. In Poland in 2012 the incidence of tuberculosis was higher than the average in EU countries. The highest incidence rates occurred in older age groups. The incidence in men was more than 2 times higher than in women. The incidence of tuberculosis in children and the percentage of patients with drug-resistant tuberculosis are lower than average in EU and that is favorable for epidemiological situation of tuberculosis in our country. PMID- 25135519 TI - An unusual case of collagenous gastritis in a middle- aged woman with systemic lupus erythromatosis: a case report. AB - INTRODUCTION: Collagenous gastritis is a rare histopathologic disease. It is characterized by marked subepithelial collagen deposition with associated inflammatory infiltrate. It is considered an uncommon disease among the general population. Collagenous gastritis without colonic involvement is an extremely rare disease. It is not known to be associated with systemic lupus erythromatosis. This is the first report of this type of association. CASE PRESENTATION: We present a 47-year-old woman from southeast Asia with dyspepsia and mild anemia. Her past medical history was significant for systemic lupus erythromatosis, autoimmune hemolytic anemia as well as hypothyroidism. Her gastroscopy and colonoscopy results were normal from an endoscopic point of view. However, the histopathology showed collagenous gastritis. CONCLUSIONS: To the best of our knowledge, this is the first case reported of a patient with systemic lupus erythromatosis associated with collagenous gastritis. Further studies are needed to evaluate the association between both diseases from a pathophysiological and immunological perspective. PMID- 25135521 TI - Flower opening and closure: an update. AB - This review is an update of a 2003 review (Journal of Experimental Botany 54,1801 1812) by the same corresponding author. Many examples of flower opening have been recorded using time-lapse photography, showing its velocity and the required elongation growth. Ethylene regulates flower opening, together with at least gibberellins and auxin. Ethylene and gibberellic acid often promote and inhibit, respectively, the expression of DELLA genes and the stability of DELLA proteins. DELLA results in growth inhibition. Both hormones also inhibited and promoted, respectively, the expression of aquaporin genes required for cell elongation. Arabidopsis miRNA319a mutants exhibited narrow and short petals, whereby miRNA319a indirectly regulates auxin effects. Flower opening in roses was controlled by a NAC transcription factor, acting through miRNA164. The regulatory role of light and temperature, in interaction with the circadian clock, has been further elucidated. The end of the life span in many flowers is determined by floral closure. In some species pollination resulted in earlier closure of turgid flowers, compared with unpollinated flowers. It is hypothesized that this pollination-induced effect is only found in flowers in which closure is regulated by ethylene. PMID- 25135520 TI - A comparative study of ripening among berries of the grape cluster reveals an altered transcriptional programme and enhanced ripening rate in delayed berries. AB - Transcriptional studies in relation to fruit ripening generally aim to identify the transcriptional states associated with physiological ripening stages and the transcriptional changes between stages within the ripening programme. In non climacteric fruits such as grape, all ripening-related genes involved in this programme have not been identified, mainly due to the lack of mutants for comparative transcriptomic studies. A feature in grape cluster ripening (Vitis vinifera cv. Pinot noir), where all berries do not initiate the ripening at the same time, was exploited to study their shifted ripening programmes in parallel. Berries that showed marked ripening state differences in a veraison-stage cluster (ripening onset) ultimately reached similar ripeness states toward maturity, indicating the flexibility of the ripening programme. The expression variance between these veraison-stage berry classes, where 11% of the genes were found to be differentially expressed, was reduced significantly toward maturity, resulting in the synchronization of their transcriptional states. Defined quantitative expression changes (transcriptional distances) not only existed between the veraison transitional stages, but also between the veraison to maturity stages, regardless of the berry class. It was observed that lagging berries complete their transcriptional programme in a shorter time through altered gene expressions and ripening-related hormone dynamics, and enhance the rate of physiological ripening progression. Finally, the reduction in expression variance of genes can identify new genes directly associated with ripening and also assess the relevance of gene activity to the phase of the ripening programme. PMID- 25135522 TI - Microtubule array reorientation in response to hormones does not involve changes in microtubule nucleation modes at the periclinal cell surface. AB - Aligned microtubule arrays spatially organize cell division, trafficking, and determine the direction of cell expansion in plant cells. In response to changes in environmental and developmental signals, cells reorganize their microtubule arrays into new configurations. Here, we tested the role of microtubule nucleation during hormone-induced microtubule array reorientation. We have found that in the process of microtubule array reorientation the ratios between branching, parallel, and de-novo nucleations remained constant, suggesting that the microtubule reorientation mechanism does not involve changes in nucleation modes. In the ton2/fass mutant, which has reduced microtubule branching nucleation frequency and decreased nucleation activity of the gamma-tubulin complexes, microtubule arrays were able to reorient. Presented data suggest that reorientation of microtubules into transverse arrays in response to hormones does not involve changes in microtubule nucleation at the periclinal cell surface. PMID- 25135524 TI - The effect of duty hour regulation on resident surgical case volume in otolaryngology. AB - OBJECTIVE: Evaluate the effect of duty hour regulation on graduating otolaryngology resident surgical case volume and analyze trends in surgical case volume for Accreditation Council for Graduate Medical Education (ACGME) key indicator cases from 1996 to 2011. STUDY DESIGN: Time-trend analysis of surgical case volume. SETTING: Nationwide sample of otolaryngology residency programs. SUBJECTS: Operative logs from the American Board of Otolaryngology and ACGME for otolaryngology residents graduating in the years 1996 to 2011. METHODS: Key indicator volumes and grouped domain volumes before and after resident duty hour regulations (2003) were calculated and compared. Independent t test was performed to evaluate overall difference in operative volume. Wilcoxon rank sum test evaluated differences between procedures per time period. Linear regression evaluated trend. RESULTS: The average total number of key indicator cases per graduating resident was 440.8 in 1996-2003 compared to 500.4 cases in 2004-2011, and overall average per number of key indicators was 31.5 and 36.2, respectively (P = .067). Four key indicator cases showed statistically significant (P < .05) increases in volume after duty hour implementation. General/pediatrics was the only grouped domain to show a significant increase. In contrast, the rate of change in operative volume decreased post duty hour for only 2 key indicators (P < .05). The year-by-year trend in average operative volume showed significant increases for 5 key indicator cases (P < .05). CONCLUSION: Implementation of the 2003 duty hour regulations has not reduced total volume of key indicator cases for graduating otolaryngology residents. The overall trend in operative volume is increasing for several specific key indicators. PMID- 25135523 TI - In vivo tmRNA protection by SmpB and pre-ribosome binding conformation in solution. AB - TmRNA is an abundant RNA in bacteria with tRNA and mRNA features. It is specialized in trans-translation, a translation rescuing system. We demonstrate that its partner protein SmpB binds the tRNA-like region (TLD) in vivo and chaperones the fold of the TLD-H2 region. We use an original approach combining the observation of tmRNA degradation pathways in a heterologous system, the analysis of the tmRNA digests by MS and NMR, and co-overproduction assays of tmRNA and SmpB. We study the conformation in solution of tmRNA alone or in complex with one SmpB before ribosome binding using SAXS. Our data show that Mg(2+) drives compaction of the RNA structure and that, in the absence of Mg(2+), SmpB has a similar effect albeit to a lesser extent. Our results show that tmRNA is intrinsically structured in solution with identical topology to that observed on complexes on ribosomes which should facilitate its subsequent recruitment by the 70S ribosome, free or preloaded with one SmpB molecule. PMID- 25135526 TI - Placement of an internal-external biliary drain through a bilio-enteric fistula in a neonate to re-establish antegrade bile flow after liver transplantation. AB - Three-month-old baby girl with history of post-liver transplant hepatic artery dissection treated with ligation after take down of the biliary anastomosis and placement of a surgical external common bile duct drain. There was persistent malfunction of this drain. A bilio-enteric fistula was noted during the later placement of an image guided percutaneous external drain. Subsequently, an internal-external biliary drain was successfully placed through this fistula. An excellent clinical and functional result was achieved. PMID- 25135528 TI - A personal journal journey. PMID- 25135525 TI - Head and neck sarcomas: analysis of the SEER database. AB - OBJECTIVE: To summarize the epidemiology of sarcomas occurring in the head and neck and identify prognostic factors for patient survival. STUDY DESIGN AND SETTING: Cross-sectional analysis of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program. METHODS: The SEER 18 registries, comprising sarcoma diagnoses made from 1973 to 2010, were queried for sarcomas arising in the head and neck. Pediatric and adult patients were analyzed separately, and multivariate and propensity-matched analyses were performed to identify predictors of disease-specific survival. RESULTS: In all, 11,481 adult cases and 1244 pediatric cases were identified. In adults, the most common histologic subtypes were malignant fibrous histiocytoma (MFH), Kaposi sarcoma, and hemangiosarcoma, while in the pediatric cohort, the most common histologic subtypes were rhabdomyosarcoma, MFH, and osteosarcoma. Cause-specific 2-, 5-, and 10-year survival rates were 76%, 66%, and 61% for adults and 84%, 73%, and 71% for pediatric patients. Multivariate analysis performed for adults revealed that male gender, absence of radiation therapy, and stage I disease were associated with improved cause-specific survival reaching statistical significance. However, a propensity-matched model demonstrated no significant difference in cause specific survival between patients who received radiation and those who did not. CONCLUSION: Sarcomas, a heterogeneous group of malignant mesenchymal tumors, are uncommonly found in the head and neck. This study represents the largest analysis of patients with head and neck sarcomas in the literature and demonstrates the impact of age, gender, primary site, histology, and radiation status on overall prognosis. PMID- 25135527 TI - Refractive corneal lenticule extraction. PMID- 25135529 TI - Intraocular lens scaffold to facilitate intraocular lens exchange. AB - We describe a technique of intraocular lens (IOL) exchange in patients with post refractive surgery IOL power error or patients who are dissatisfied with the optical performance of the IOL. The technique involves the presence of 2 IOLs in the eye: the offending IOL, which is manipulated out of the capsular bag into the anterior chamber, and the corrective IOL, which is inserted into the bag. The anteriorly elevated IOL is transected with the IOL cutting scissors, while the corrective IOL acts as a scaffold for the posterior capsule. The technique provides continuous distension of the bag with the IOL, which prevents damage to the posterior capsule and acts as a barrier to vitreous prolapse in cases of an open posterior capsule; it also prevents slippage of the optic during transection of the IOL being removed. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135530 TI - Phacoemulsification using 8 flexible iris hooks in a patient with a short eye, small pupil, and phacodonesis. AB - We describe a technique that uses flexible iris hooks to dilate and stabilize the capsular bag in a patient with a very deep set and small eye, narrow palpebral fissure, shallow anterior chamber, and very small pupil, who was scheduled for routine phacoemulsification for a white cataract. At the time of iris hook placement, the capsular bag was noted to be markedly unstable. The patient was managed successfully with phacoemulsification of the lens using 4 iris hooks to dilate the pupil and 4 iris hooks to stabilize the capsular bag during surgery. A foldable posterior chamber 3-piece intraocular lens was fixated in the ciliary sulcus. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned. PMID- 25135531 TI - Closure technique for leaking wound resulting from thermal injury during phacoemulsification. AB - We describe a method of wound closure with a conjunctival flap in cases of wound burn. A fornix-based conjunctival flap is raised to adequately cover the wound. Then, a single horizontal mattress suture with 10-0 monofilament nylon is passed to appose the wound. The conjunctival flap is hinged to the corneal end of the loop so the conjunctival flap covers the wound when the suture is tied. The wound is thus sealed by conjunctiva with optimum suture tension. This suture was applied in 5 patients with clear corneal incisions who developed wound burn during phacoemulsification. All had an uneventful recovery with a sealed wound from the first postoperative day and satisfactory visual outcomes with low residual astigmatism at the final refraction. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary interest in any material or method mentioned. PMID- 25135532 TI - Refractive lenticule extraction: transition and comparison of 3 surgical techniques. AB - PURPOSE: To describe the transition and outcomes of 3 refractive lenticule extraction (ReLEx) techniques: femtosecond lenticule extraction (FLEx), small incision lenticule extraction (SMILE), and pseudo small-incision lenticule extraction. SETTING: Singapore National Eye Center, Singapore. DESIGN: Prospective comparative case series. METHODS: Refractive lenticule extraction was performed between March 1, 2010, and November 1, 2012, using the Visumax 500 kHz femtosecond laser system. The main outcome measures were the refractive efficacy, predictability, and safety over 12 months. RESULTS: The study enrolled 88 eyes. All 3 refractive lenticule extraction techniques yielded good refractive outcomes and stability over 12 months. Three months postoperatively, the mean overall efficacy index of refractive lenticule extraction was 0.89+/-0.22 (SD), with 95.5% of eyes attaining an uncorrected distance visual acuity (UDVA) of better than 20/40 and 60.2% of better than 20/20. Of all eyes, 95.5% were within +/-1.00 diopter (D) and 78.4% within +/-0.50 D of the attempted correction. The mean overall safety index was 1.06+/-0.17. At 3 months, all small-incision lenticule extraction eyes and 96.7% of pseudo small-incision lenticule extraction eyes had a UDVA of 20/40 or better, while femtosecond lenticule extraction eyes had a lower efficacy index (87.0%). However, efficacy was comparable in all 3 groups by 12 months (mean 0.87+/-0.04 [standard error of the mean]; P=1.00). CONCLUSION: The efficacy, safety, and predictability profiles of the 3 refractive lenticule extraction techniques were good over a 12-month follow-up. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135533 TI - Five-year results of refractive lenticule extraction. AB - PURPOSE: To evaluate the 5-year results of femtosecond laser-assisted refractive lenticule extraction (ReLEx-FLEx) for the treatment of myopia and myopic astigmatism. SETTING: Departments of Ophthalmology, Helios Klinikum Erfurt, Erfurt, and Phillips Universitat Marburg, Marburg, Germany. DESIGN: Prospective clinical trial. METHODS: This was a follow-up of a prospective study that evaluated the first patients treated with refractive lenticule extraction, in which a flap and a refractive lenticule of intrastromal corneal tissue were simultaneously cut using a 200 kHz Visumax femtosecond laser system. Thereafter, the lenticule was manually removed and the flap repositioned. The main outcome measures were the uncorrected and corrected distance visual acuities, objective and manifest refractions, slitlamp examination findings, and side effects after 5 years. RESULTS: Forty-one of 108 eyes in the original treatment group were available for a reexamination. Five years postoperatively, 100% of eyes were within +/-1.00 diopter (D) of the intended correction and 73% were within +/-0.50 D. By 5 years, no eye had lost 2 or more Snellen lines and 1 eye had lost 1 Snellen line. The mean regression was 0.07 D. CONCLUSION: Long-term data indicate that refractive lenticule extraction is an effective and safe procedure for the treatment of myopia and myopic astigmatism and has excellent stability. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135534 TI - Simultaneous topography-guided partial photorefractive keratectomy and corneal collagen crosslinking for keratoconus. AB - PURPOSE: To report the visual, refractive, and clinical outcomes of simultaneous topography-guided partial photorefractive keratectomy (PRK) and corneal collagen crosslinking (CXL) in eyes with keratoconus. SETTING: Private practice surgery center, Dubai, United Arab Emirates. DESIGN: Retrospective cohort study. METHODS: Refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, flat and steep keratometry (K) readings, and complications were evaluated 1, 3, 6, and 12 months postoperatively. RESULTS: The study enrolled 31 eyes of 31 patients aged 21 to 42 years. All study parameters showed a statistically significant improvement at 3, 6, and 12 months over baseline values. At 12 months, the mean UDVA improved to 0.23 logMAR+/-0.33 (SD) from 0.79+/-0.36 logMAR (P<.001) and the CDVA improved to 0.06+/-0.07 logMAR from 0.28+/-0.20 logMAR (P<.001). The mean defocus decreased from 3.45+/-1.60 diopters (D) to 1.88+/-1.58 D (P<.001). The flat K and steep K readings showed significant flattening. The mean refractive astigmatism decreased from -2.77+/-1.47 D to -0.98+/-0.76 D (P<.001). The improvement in study parameters plateaued after 3 months. CONCLUSION: Simultaneous topography-guided partial PRK and CXL was effective, safe, and stable in keratoconus patients. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135535 TI - Long-term results of combined transepithelial phototherapeutic keratectomy and corneal collagen crosslinking for keratoconus: Cretan protocol. AB - PURPOSE: To present the long-term results of combined transepithelial phototherapeutic keratectomy (PTK) and corneal collagen crosslinking (CXL) for keratoconus. SETTING: Vardinoyiannion Eye Institute of Crete, University of Crete, Heraklion, Crete, Greece. DESIGN: Prospective case series. METHODS: Patients with progressive keratoconus had combined transepithelial PTK and CXL (Cretan protocol). Visual and refractive outcomes and the endothelial cell density (ECD) were evaluated preoperatively and postoperatively. RESULTS: Twenty patients (23 eyes) were enrolled; postoperatively 23 eyes were evaluated at 1 and 2 years, 11 at 3 years, and 7 at 4 years. The mean follow-up was 33.83 months+/ 10.82 (SD) (range 24 to 56 months). No intraoperative or postoperative complications occurred. The mean uncorrected distance visual acuity improved significantly from 0.99+/-0.57 logMAR preoperatively to 0.61+/-0.36 logMAR at the last follow-up (P<.001) and the mean corrected distance visual acuity, from 0.27+/-0.24 logMAR to 0.17+/-0.14 logMAR (P=.018), respectively. The mean steep and mean flat keratometry readings decreased significantly from 53.39+/-7.14 diopters (D) and 47.17+/-4.87 D, respectively, preoperatively to 49.99+/-4.36 D (P<.001) and 45.47+/-2.95 D (P=.002), respectively, at the last follow-up. The mean corneal astigmatism improved significantly from -6.27+/-4.19 D preoperatively to -4.52+/-2.80 D (P<.001) at the last follow-up. No significant ECD alterations occurred (P>.05). CONCLUSION: Combined transepithelial PTK and CXL was effective and safe in keratoconic patients over a long-term follow-up. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135536 TI - Corneal resistance factor and corneal hysteresis in a 6- to 18-year-old population. AB - PURPOSE: To determine the distribution and normal range of the corneal resistance factor (CRF) and corneal hysteresis (CH) in the 6- to 18-year age range and their relationship with biometric components. SETTING: Dezful, Iran. DESIGN: Cross sectional study. METHODS: This study of Dezful school children used a multistage, stratified, cluster approach sampling. All students had examinations for biometry, noncycloplegic refraction, and corneal biomechanical properties; the examinations were performed in the same order in all cases. RESULTS: Of the 864 selected students, 683 participated in the study. The mean CRF and CH was 11.74 mm Hg+/-1.77 (SD) (95% confidence interval [CI], 11.58-11.89) and 11.49+/-1.91 mm Hg (95% CI, 11.33-11.65), respectively. In a linear multiple regression model, the CRF significantly correlated with female sex (beta coefficient=0.488, P=.013), central corneal thickness (CCT) (beta coefficient=.034, P=.001), and keratometry (beta-coefficient=0.157, P=.003) and CH significantly correlated with CCT (beta coefficient=0.025, P<.001), axial length (beta coefficient=-0.303, P=.011), and keratometry (beta coefficient=0.11, P=.043). Each year increase in age was associated with a 42-unit decrease in the peak 1 area (P=.003). CONCLUSIONS: The distribution of CRF and CH in an Iranian population was symmetrical and bell shaped. However, the CRF did not have a normal distribution. The mean CRF and CH were higher than those reported in almost all previous studies. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135537 TI - Long-term ultrasound biomicroscopy observation of position changes of a copolymer posterior chamber phakic intraocular lens. AB - PURPOSE: To evaluate longitudinal changes in Implantable Collamer Lens phakic intraocular lens (pIOL) position after implantation. SETTING: Department of Ophthalmology, Zhejiang University, Hangzhou, China. DESIGN: Retrospective case series. METHODS: Myopic eyes that had pIOL implantation with a follow-up of at least 24 months were evaluated. Ultrasound biomicroscopy examinations were performed at each visit. RESULTS: The study enrolled 62 eyes (31 patients; 22 women, 9 men) ranging in age from 21 to 46 years. The manifest spherical equivalent ranged from -8.25 to -18.75 diopters. A significant increase (mean 36 MUm+/-50 [SD]) in the endothelium-anterior pIOL distance occurred between 1 month and 3 months (P=.000); afterward, the distance decreased slowly (P>.05). The largest decrease (mean 47+/-17 MUm) in central vault occurred between 1 month and 3 months (P=.009). The largest decrease (mean 21+/-14 MUm) in peripheral vault occurred between 1 month and 3 months (P=.000). CONCLUSIONS: A significant increase in the endothelium-anterior pIOL distance occurred from 1 month to 3 months postoperatively, after which a slight decrease occurred over time. Central vault and peripheral vault had a tendency to decrease over time. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135538 TI - Evaluation of an electronic reading desk to measure reading acuity in pseudophakic patients. AB - PURPOSE: To compare a new electronic reading desk (Salzburg-Advanced) with conventional measurements of reading acuity. SETTING: Vienna Institute for Research in Ocular Surgery, Hanusch Hospital, Vienna, Austria. DESIGN: Evaluation of diagnostic test. METHODS: In study 1, the electronic reading desk was compared with the same version of a printed reading chart. All patients were measured twice with autorefraction (Topcon KR8800) and subjective refraction. In study 2, patients were measured once. In addition, electronic reading desk measurements were obtained under different contrast and luminance levels. RESULTS: Study 1 evaluated 100 eyes of 50 pseudophakic patients. Differences between the electronic reading desk and the printed version were small and not significant for reading speed (131.1 words per minute [wpm]+/-28.7 [SD] versus 134.9+/-20.7 wpm), reading distance (44.7+/-14.4 cm versus 39.6+/-7.6 cm), and smallest possible read print size (1.95+/-0.58 mm versus 2.02+/-0.70 mm), respectively. Study 2 evaluated 40 eyes of 20 pseudophakic patients. Reading acuity and the smallest possible read print size decreased with lower contrast and reduced luminance, whereas reading distance and reading speed did not change significantly. CONCLUSIONS: Measurements performed with the electronic reading desk can be used interchangeably with those performed using a printed chart. The opportunity to preset standardized luminance and contrast settings could be useful for measurements in clinical trials. FINANCIAL DISCLOSURES: Drs. Dexl and Grabner have a proprietary interest in the Salzburg Reading Desk technology as patent assignees. No other author has a financial or proprietary interest in any material or method mentioned. PMID- 25135539 TI - Influence of intraocular lens haptic design on refractive error. AB - PURPOSE: To assess the influence of intraocular (IOL) haptic design on the refraction prediction error in patients having cataract surgery. SETTING: Private practice. DESIGN: Comparative case series. METHODS: Corneal power and axial length were measured with the same devices in eyes with a 3-piece Acrysof IOL and eyes with a 1-piece Acrysof IOL and were entered into the Haigis, Hoffer Q, Holladay 1, and SRK/T formulas. The median absolute error and mean absolute error in refraction prediction (ie, difference between expected refraction and actual refraction) were assessed 1 month postoperatively. RESULTS: The study evaluated 110 eyes with the 3-piece IOL and 84 eyes with the 1-piece IOL. With all formulas, the median absolute error was lower with the 3-piece IOL. It ranged between 0.15 diopter (D) (Haigis and Holladay 1) and 0.19 D (SRK/T) with the 3 piece IOL and between 0.23 D (Haigis) and 0.30 D (SRK/T) with the 1-piece IOL. With all formulas, a higher percentage of eyes with the 3-piece IOL were within +/-0.25 D and +/-0.50 D of the target refraction. CONCLUSIONS: Three-piece IOLs may yield better refractive outcomes than 1-piece IOLs. A possible reason is that once the early forward IOL shift previously observed with the 3-piece design occurs because of the haptic-compression force decay typical of these IOLs, the rigid haptics of 3-piece IOLs still exert more pressure against the capsular bag than the haptics of 1-piece IOLs. Therefore, 3-piece IOLs may better resist subsequent capsule contraction and provide a more predictable effective lens position. FINANCIAL DISCLOSURE: Dr. Hoffer receives royalties for his book IOL Power, Slack, Inc., and formula royalties from all manufacturers using the Hoffer Q formula. No other author has a financial or proprietary interest in any material or method mentioned. PMID- 25135540 TI - Clinical outcomes and rotational stability of a 4-haptic toric intraocular lens in myopic eyes. AB - PURPOSE: To evaluate the refractive outcomes and rotational stability of a 4 haptic toric intraocular lens (IOL) in myopic eyes and the correlations between IOL rotation and refractive sphere, axial length (AL), and white-to-white (WTW) diameter. SETTING: Eye Clinic, Careggi Hospital, Florence, Italy. DESIGN: Prospective case series. METHODS: Phacoemulsification cataract extraction and implantation of an AT Torbi 709M IOL were performed. Corneal astigmatism was 1.50 diopters (D) or greater and the AL between 25.0 mm and 27.0 mm in all eyes. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, and IOL axis were evaluated preoperatively and postoperatively up to 6 months. RESULTS: The study enrolled 20 eyes (20 patients). The UDVA and CDVA improved significantly postoperatively (P<.001). The mean refractive spherical equivalent decreased significantly from -7.10 D+/-1.78 (SD) preoperatively to -0.55+/-0.25 D 1 day postoperatively (P<.001) and remained stable thereafter. Vector analysis showed that 90% and 85% of the eyes were within +/-0.25 D for J0 and J45, respectively. At 3 months and 6 months, the mean IOL rotation was 2.66+/-1.53 degrees and 3.00+/-1.69 degrees, respectively (P<.001), with 95% of eyes and 90% of eyes, respectively, within +/-5 degrees. A positive correlation was found between IOL rotation and preoperative sphere; none was found with AL and WTW. CONCLUSIONS: Implantation of the 4-haptic toric IOL in myopic eyes was effective and safe. The IOL showed no significant rotation over the 6-month follow-up. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135541 TI - Pars plana vitrectomy combined with iris-claw intraocular lens implantation for lens nucleus and intraocular lens dislocation. AB - PURPOSE: To assess the medium-term efficacy and safety of treating nucleus and intraocular lens (IOL) dislocation with pars plana vitrectomy (PPV) combined with iris-claw IOL implantation. SETTING: Department of Ophthalmology, University of Lyon 1 Claude Bernard, Lyon, France. DESIGN: Retrospective case series. METHODS: The study comprised consecutive patients without capsule support having PPV combined with iris-claw IOL implantation for posterior dislocation of the nucleus or IOL between 2008 and 2012. The preoperative, intraoperative, and postoperative data were retrospectively analyzed. Patients were invited to a prospective final examination at least 6 months postoperatively. RESULTS: The study enrolled 32 eyes (31 consecutive patients). The dislocation was spontaneous in 8 cases and traumatic in 24 (intraoperative 17 cases, contusive 7 cases). The iris-claw IOL was on the anterior side of the iris in 19 cases and on the posterior side in 13 cases. The mean corrected distance visual acuity at the end of follow-up was 20/40 or better in 22 patients (69%). The mean spherical equivalent was +8.20 (SD)+/-6.03 diopters (D) preoperatively and -0.51+/-1.14 D postoperatively. The median endothelial cell loss was 20.5% over the first 3 months. The complications were cystoid macular edema (n=8), retinal detachment (n=4), transient intravitreal hemorrhage (n=4), secondary glaucoma (n=2), and choroidal detachment (n=1). The final examination was performed in 27 eyes. CONCLUSION: Treatment of nucleus and IOL dislocation with PPV combined with iris-claw IOL implantation was effective and safe over the medium-term. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135542 TI - Nepafenac 0.1% plus dexamethasone 0.1% versus dexamethasone alone: effect on macular swelling after cataract surgery. AB - PURPOSE: To evaluate the efficacy of adding nepafenac 0.1% ophthalmic suspension to dexamethasone 0.1% eyedrops in controlling macular swelling and other manifestations of inflammation after uneventful cataract surgery. SETTING: Ophthalmology Department, Molndal Hospital, Gothenburg, and St. Erik Eye Hospital, Stockholm, Sweden. DESIGN: Randomized double-masked clinical trial. METHODS: Patients at low risk for postoperative inflammation were recruited and randomized to the nepafenac group or to the control group. Postoperative swelling of the macula was assessed with ocular coherence tomography. Laser flare intensity, corrected distance visual acuity, ocular discomfort, and visual complaints were also recorded. RESULTS: The analysis of intent-to-treat population comprised 75 patients in the nepafenac group and 77 patients in the control group. Compared with the control regimen, add-on nepafenac resulted in statistically significant reductions in the following parameters: change in macular volume at 3 weeks and 6 weeks (P<.001), proportion of patients with more than 10 MUm of swelling in the central macula at 3 weeks (P<.0001) and 6 weeks (P=.02), mean laser flare intensity at 1 day (P=.029), pain during the first 24 hours postoperatively (P<.0001), and ocular discomfort and photophobia during the first 3 postoperative weeks (P=.0058 and P=.0052, respectively). CONCLUSION: The combination of topical nepafenac and steroid treatment reduced subclinical macular swelling and inflammation as well as subjective complaints, indicating it is an efficient antiinflammatory regimen after cataract surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135543 TI - Evaluating teaching methods: validation of an evaluation tool for hydrodissection and phacoemulsification portions of cataract surgery. AB - PURPOSE: To develop and assess the validity of an evaluation tool to assess quantitatively the hydrodissection and phacoemulsification portions of cataract surgery performed by residents. DESIGN: Case series. SETTING: Jules Stein Eye Institute, Olive View-UCLA Medical Center, and Veterans Administration Medical Center, Los Angeles, California, USA. METHODS: The UCLA ophthalmology faculty members were surveyed and the literature was reviewed to develop a grading tool consisting of 15 questions to evaluate surgical technique, including questions from the Global Rating Assessment of Skills in Intraocular Surgery and from the International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric. Video clips of the hydrodissection and phacoemulsification portions of cataract surgery performed by 1 postgraduate year 2 (PGY2) resident, 1 PGY3 resident, 2 PGY4 residents, and an advanced surgeon were independently graded in a masked fashion by an 8-member faculty panel. RESULTS: Eleven of the 15 questions had a significant association with surgical experience level (P<.05, analysis of variance). Interobserver variability in grading yielded intraclass correlation coefficients between 0.28 and 0.72. The questions with the lowest interobserver variability were hydrodissection questions on instrument handling, flow of operation, and nucleus rotation. Nucleus cracking also had low variability. Less directly visible tasks, especially 3-dimensional tasks, had wider interobserver variability. CONCLUSIONS: Surgical performance can be validly measured using an evaluation tool. Improved videography and studies to identify the best questions for evaluating each step of cataract surgery may help ophthalmic educators more precisely measure training outcomes for improving teaching interventions. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135544 TI - Textural interface opacity after Descemet-stripping automated endothelial keratoplasty. AB - PURPOSE: To describe cases of interface haze, also known as textural interface opacity, after Descemet-stripping automated endothelial keratoplasty (DSAEK). SETTING: Department of Cornea, External Disease, and Refractive Surgery Service, Duke Eye Center, Durham, North Carolina, USA. DESIGN: Retrospective case series. METHODS: Patients' clinical and demographic characteristics, cornea donor information, surgical technique, histopathology, and anterior segment optical coherence tomography (OCT) were reviewed retrospectively and clinical outcomes reported. RESULTS: The interface haze that developed after DSAEK comprised 2 types of textural interface opacity; that is, total (11 cases) and partial (3 cases). The time of onset of textural interface opacity ranged from 1 day to 7 weeks postoperatively. Although most patients with textural interface opacity showed improvement, with a corrected distance visual acuity better than 20/50, 3 had persistent decreased visual acuity and required repeat DSAEK. Seven eyes had concurrent phacoemulsification with intraocular lens implantation and DSAEK. The corneal graft was inserted with an Endoserter device in 11 eyes, an insertion forceps in 2 eyes, and a cystotome needle in 1 eye. Histopathology of the grafts of eyes that required repeat DSAEK showed no inflammation, no foreign-body deposit, and no fibrosis. Anterior segment OCT showed increased hyperreflectivity in the interface. CONCLUSIONS: Although the etiology of textural interface opacity is unclear, it may be related to retained ophthalmic viscosurgical device (OVD) or an adhesive property of the OVD used during the surgery. Although most cases resolve with time, repeat DSAEK may be an effective treatment for refractory cases. FINANCIAL DISCLOSURE: Dr. Kim is a consultant to Ocular Systems, Inc. No other author has a financial or proprietary interest in any material or method mentioned. PMID- 25135545 TI - Prevention of capsule opacification after accommodating lens refilling: pilot study of strategies evaluated in a monkey model. AB - PURPOSE: To test 2 strategies to prevent capsule opacification after accommodating lens refilling in a rhesus monkey model. SETTING: Animal laboratory and laboratory of European university medical centers. DESIGN: Experimental study. METHODS: Six rhesus monkeys had refilling of the lens capsular bag. In the first strategy, before it was filled with a silicone polymer, the capsular bag was treated with noncommercial sodium hyaluronate 1.0% containing cytotoxic substances. In the second strategy, the capsular bag was filled with clinically used sodium hyaluronate 1.0% (Healon) after treatment with actinomycin-D. Slitlamp inspection was performed during a follow-up of 40 to 50 weeks. After enucleation, magnetic resonance images were obtained and confocal fluorescence imaging was performed. RESULTS: Using the first strategy, capsule opacification developed in all eyes. Using the second strategy, 1 monkey did not develop capsule opacification after a 9-month follow-up. In a second monkey, the lens capsule remained clear for 3 months, after which the hyaluronate refill material was exchanged with a silicone polymer and capsule opacification developed. Combining these results with those in a previous study, the difference in opacification between silicone and sodium hyaluronate as refilling materials was statistically significant (P<.01). CONCLUSIONS: That no capsular bag fibrosis occurred in the presence of hyaluronate suggests that the properties of hyaluronate are the reason that remaining lens epithelial cells do not develop into fibrotic cells. The choice of a suitable lens-refilling material prevents the development of capsule opacification. FINANCIAL DISCLOSURE: Mr. Terwee was an employee of Abbott Medical Optics B.V. during the study period. No other author has a financial or proprietary interest in any material or method mentioned. PMID- 25135547 TI - Optimum on-time duty cycle for micropulse technology. AB - PURPOSE: To evaluate the optimum on time for the most efficient removal of lens fragments using micropulsed ultrasound (US). SETTING: John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Twenty porcine lens nuclei were soaked in formalin for 2 hours and then divided into 2.0 mm cubes. Using an US machine with a 0.9 mm bent and a 30-degree bevel tip, the on time was varied every millisecond (ms) from 2 ms to 10 ms with the off time kept constant at 10 ms. Efficiency (time to lens removal) and chatter (number of lens fragment repulsions from the tip) were determined. RESULTS: The most efficient phacoemulsification was achieved with an on time of 6 ms. On times shorter than 6 ms were significantly less efficient (R2=.82, P=.04). Greater on times did not result in a significant difference in efficiency (R2=.03, P=.78) but did appear to have more chatter events when comparing 9 to 10 ms with 2 to 8 ms (P<.0001). CONCLUSIONS: With micropulsed longitudinal US, a 6 ms on time was equally as efficient as longer on times, while shorter on times (2 to 5 ms) had decreased efficiency. At 9 ms and 10 ms on time, significantly more chatter was noted. Therefore, to maximize phacoemulsification, an on-time setting of 6 ms is recommended. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135546 TI - Biointerface multiparametric study of intraocular lens acrylic materials. AB - PURPOSE: To compare hydrophilic and hydrophobic acrylic materials designed for intraocular lenses in a multiparametric investigation in a liquid environment to highlight their properties in terms of adhesion forces, lens epithelial cell (LEC) adhesion, and tissue response as indicators of the risk for posterior capsule opacification (PCO) development. SETTING: University of Liege, Liege, Belgium. DESIGN: Experimental study. METHODS: The hydrophobicity and surface adhesion force were assessed using contact-angle and atomic force microscopy measurements. The bioadhesiveness of the disks and the tissue response were determined by in vitro experiments using bovine serum albumin and porcine LECs and by in vivo rabbit subcutaneous implantation, respectively. RESULTS: Increasing surface hydrophobicity led to a greater surface-adhesion force and greater LEC adhesion. After 1 month, the rabbit subcutaneous implants showed a similar thin layer of fibrous capsule surrounding the disks without extensive inflammation. A layer of rounded cells in contact with disks was detected on the hydrophobic samples only. CONCLUSIONS: Hydrophobic acrylic disks that have been associated with a reduced risk for PCO in clinical studies showed increased tackiness. FINANCIAL DISCLOSURES: Proprietary or commercial disclosures are listed after the references. PMID- 25135548 TI - Microincisions in cataract surgery. AB - Improvements in phacoemulsification technology and instrumentation and intraocular lens materials and design have enabled cataract surgery to be performed through incisions smaller than 2.0 mm in external width. This evolution has occurred over time, with new challenges arising at each step of the decrease in incision size. This article reviews the current trend of using increasingly smaller incisions to perform phacoemulsification. Specifically, each facet of phacoemulsification is briefly reviewed from a historical context and then evaluated predominantly from a current perspective to better understand the development of the microincision in cataract surgery. The goal is to help the operating surgeon recognize the potential benefits as well as the potential weaknesses of the smaller incision. FINANCIAL DISCLOSURES: Proprietary or commercial disclosures are listed after the references. PMID- 25135549 TI - Corneal collagen crosslinking failure in a patient with floppy eyelid syndrome. AB - A 30-year-old man with bilateral floppy eyelid syndrome (more prominent in the left eye) and progressive keratoconus had corneal collagen crosslinking (CXL) in both eyes. No intraoperative or early postoperative complications were found. Topographic examination after CXL revealed a continuous increase in the keratometric values in the left eye in which the floppy eyelid syndrome was more prominent, indicating keratoconus progression (CXL failure). The fellow eye with the less prominent floppy eyelid syndrome remained stable during the follow-up period. Floppy eyelid syndrome could be a risk factor for CXL failure. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135550 TI - Spontaneous bilateral anterior partial in-the-bag intraocular lens dislocation following routine annual eye examination. AB - We present the case of an 81-year-old man with pseudoexfoliation syndrome (PXF) in whom spontaneous bilateral anterior partial in-the-bag intraocular lens (IOL) dislocation was diagnosed following a routine dilated examination that demonstrated only mild pseudophacodonesis with no evidence of subluxation. Uneventful cataract surgery with placement of single-piece hydrophobic acrylic posterior chamber IOLs had been performed in both eyes 7 years previously. Bilateral IOL repositioning with scleral fixation was performed to correct the dislocation. Postoperative examinations showed remarkable improvement in visual acuity and IOL stability. We hypothesize that zonular weakness secondary to PXF predisposed the patient to bilateral IOL partial dislocation. Pupil dilation in the setting of mild pseudophacodonesis at the time of routine examination may have been a precipitating factor. To our knowledge, bilateral IOL subluxation/dislocation has been described in a limited number of case reports. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135551 TI - Unsutured phakic implantation of a black intraocular lens in the sulcus to treat leukocoria. AB - We describe a 40-year-old woman with von Hippel-Lindau syndrome, secondary chronic exudative retinal detachment, and white cataract with consequent leukocoria. Because the cataract was contracted and calcified, a black Morcher 85F poly(methyl methacrylate) IOL was implanted in the ciliary sulcus anterior to the lens to prevent posterior capsule rupture and potential destabilization of the retinal detachment with a risk for phthisis. Excellent centration of the black IOL was achieved with good cosmetic outcome and without postoperative uveitis or glaucoma. We suggest that this is a rare indication for implantation of an IOL designed for the sulcus but in the presence of the crystalline lens. This approach makes IOL removal, if necessary at a later date, relatively straightforward. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 25135552 TI - Simple method to restore a fractured 10-0 polypropylene suture using a single fisherman's knot. PMID- 25135553 TI - New benchmark in preventing phacoemulsification-related endophthalmitis. PMID- 25135554 TI - Refractive Surgical Question: September consultation #1. PMID- 25135555 TI - September consultation #2. PMID- 25135556 TI - September consultation #3. PMID- 25135557 TI - September consultation #5. PMID- 25135558 TI - September consultation #4. PMID- 25135559 TI - September consultation #7. PMID- 25135560 TI - September consultation #6. PMID- 25135567 TI - Immunology: IL-22 and metabolic disease. PMID- 25135568 TI - Cardiovascular endocrinology: controversy--cardiovascular effects of calcium supplementation. AB - Of late, clinical trial data, meta-analyses and observational studies have caused concern that the use of calcium supplements might increase the risk of myocardial infarction and stroke. A new meta-analysis suggests that there is no problem with calcium supplements, but as the analysis includes controversial data omitted from previous analyses, the debate will continue. PMID- 25135570 TI - Obesity: Targeting fat deposits--one step closer. PMID- 25135574 TI - Mode of delivery and the probability of subsequent childbearing: a population based register study. AB - OBJECTIVE: To investigate the relationship between mode of first delivery and probability of subsequent childbearing. DESIGN: Population-based study. SETTING: Nationwide study in Sweden. POPULATION: A cohort of 771 690 women who delivered their first singleton infant in Sweden between 1992 and 2010. METHODS: Using Cox's proportional-hazards regression models, risks of subsequent childbearing were compared across four modes of delivery. Hazard ratios (HRs) were calculated, using 95% confidence intervals (95% CIs). MAIN OUTCOME MEASURES: Probability of having a second and third child; interpregnancy interval. RESULTS: Compared with women who had a spontaneous vaginal first delivery, women who delivered by vacuum extraction were less likely to have a second pregnancy (HR 0.96, 95% CI 0.95 0.97), and the probabilities of a second childbirth were substantially lower among women with a previous emergency caesarean section (HR 0.85, 95% CI 0.84 0.86) or an elective caesarean section (HR 0.82, 95% CI 0.80-0.83). There were no clinically important differences in the median time between first and second pregnancy by mode of first delivery. Compared with women younger than 30 years of age, older women were more negatively affected by a vacuum extraction with respect to the probability of having a second child. A primary vacuum extraction decreased the probability of having a third child by 4%, but having two consecutive vacuum extraction deliveries did not further alter the probability. CONCLUSIONS: A first delivery by vacuum extraction does not reduce the probability of subsequent childbearing to the same extent as a first delivery by emergency or elective caesarean section. PMID- 25135576 TI - Crystal transformation synthesis of a highly stable fluorescent 3D indium tetranuclear {In4(MU2-OH)3} building block based metal organic framework through a dinuclear complex. AB - A rare 3D tetranuclear {In4(MU2-OH)3} building block based MOF {[In4/3(MU2 OH)(2,6-pydc)(1,4-bda)0.5(H2O)].2H2O}n (2) was obtained through a crystal transformation from a dimeric complex In3(2,6-pydc)3(1,4-bda)1.5(H2O)6 (1). With a 2D + 3D -> 3D compact structure, 2 retains crystallinity in boiling water and organic solvents, exhibiting exceptional fluorescence quenching behaviour for the DMSO molecule. PMID- 25135573 TI - Thyroid hormone receptors and resistance to thyroid hormone disorders. AB - Thyroid hormone action is predominantly mediated by thyroid hormone receptors (THRs), which are encoded by the thyroid hormone receptor alpha (THRA) and thyroid hormone receptor beta (THRB) genes. Patients with mutations in THRB present with resistance to thyroid hormone beta (RTHbeta), which is a disorder characterized by elevated levels of thyroid hormone, normal or elevated levels of TSH and goitre. Mechanistic insights about the contributions of THRbeta to various processes, including colour vision, development of the cochlea and the cerebellum, and normal functioning of the adult liver and heart, have been obtained by either introducing human THRB mutations into mice or by deletion of the mouse Thrb gene. The introduction of the same mutations that mimic human THRbeta alterations into the mouse Thra and Thrb genes resulted in distinct phenotypes, which suggests that THRA and THRB might have non-overlapping functions in human physiology. These studies also suggested that THRA mutations might not be lethal. Seven patients with mutations in THRalpha have since been described. These patients have RTHalpha and presented with major abnormalities in growth and gastrointestinal function. The hypothalamic-pituitary-thyroid axis in these individuals is minimally affected, which suggests that the central T3 feedback loop is not impaired in patients with RTHalpha, in stark contrast to patients with RTHbeta. PMID- 25135575 TI - Isolation of arginine kinase from Apis cerana cerana and its possible involvement in response to adverse stress. AB - Arginine kinases (AK) in invertebrates play the same role as creatine kinases in vertebrates. Both proteins are important for energy metabolism, and previous studies on AK focused on this attribute. In this study, the arginine kinase gene was isolated from Apis cerana cerana and was named AccAK. A 5'-flanking region was also cloned and shown to contain abundant putative binding sites for transcription factors related to development and response to adverse stress. We imitated several abiotic and biotic stresses suffered by A. cerana cerana during their life, including heavy metals, pesticides, herbicides, heat, cold, oxidants, antioxidants, ecdysone, and Ascosphaera apis and then studied the expression patterns of AccAK after these treatments. AccAK was upregulated under all conditions, and, in some conditions, this response was very pronounced. Western blot and AccAK enzyme activity assays confirmed the results. In addition, a disc diffusion assay showed that overexpression of AccAK reduced the resistance of Escherichia coli cells to multiple adverse stresses. Taken together, our results indicated that AccAK may be involved of great significance in response to adverse abiotic and biotic stresses. PMID- 25135577 TI - Thyroglossal duct cysts: 20 years' experience (1992-2011). AB - The objective of the present study is to report on the clinical course and management of thyroglossal duct cysts. Retrospective review of all patients who underwent surgery for thyroglossal duct cysts between 2000 and 2013 at a tertiary referral center was carried out. The operations were performed using a modification of the Sistrunk operation: transcervical cystectomy, partial dissection of the hyoid bone, and dissection of all tracts identified during surgery. A total of 352 patients (176 men, 176 women) underwent surgery for a cyst (n = 282) or discharging sinus (n = 70). The mean age for the incidence of cysts was 26 years. Four of the patients (1.4 %) had a papillary thyroid carcinoma in the epithelium of the cyst. The follow-up period ranged from 7 months to 10 years. The overall recurrence rate was 4.5 %. Resection is often regarded as an elective surgical procedure in patients with thyroglossal duct cysts, but surgery should always be considered. Papillary thyroid carcinoma in the epithelium of the cyst is a rare but possible differential diagnosis. Dissection of all tracts found is recommended and partial dissection of the hyoid bone is mandatory. Dissection of the foramen cecum is not imperative. The recurrence rates with this approach are comparable to more extensive methods such as those described by Sistrunk. PMID- 25135579 TI - Meeting report: consensus recommendations for a research agenda in exercise in solid organ transplantation. AB - With improved survival rates in solid organ transplantation there has been an increased focus on long-term outcomes following transplant, including physical function, health-related quality-of-life and cardiovascular mortality. Exercise training has the potential to affect these outcomes, however, research on the optimal timing, type, dose of exercise, mode of delivery and relevant outcomes is limited. This article provides a summary of a 2-day meeting held in April 2013 (Toronto, Canada) in which a multi-disciplinary group of clinicians, researchers, administrators and patient representatives engaged in knowledge exchange and discussion of key issues in exercise in solid organ transplant (SOT). The outcomes from the meeting were the development of top research priorities and a research agenda for exercise in SOT, which included the need for larger scale, multi-center intervention studies, development of standardized outcomes for physical function and surrogate measures for clinical trials, examining novel modes of exercise delivery and novel outcomes from exercise training studies such as immunity, infection, cognition and economic outcomes. The development and dissemination of "expert consensus guidelines," synthesizing both the best available evidence and expert opinion was prioritized as a key step toward improving program delivery. PMID- 25135578 TI - Objective assessment of persistent rhinitis in Chinese and its relationship with serum indicators. AB - Persistent rhinitis (PR) is a chronic disease that affects millions of people. However, it lacks of a useful method, which can indicate the actual severity of the inflammation in PR patients. This study was designed to seek an examination which could reflect the actual severity of PR disease. The serum Phadiatop test, ECP level, four-phase rhinomanometry, and acoustic rhinometry were assessed in 91 adult patients with PR and 10 healthy controls. The serum total IgE was determined in some of the patients and all of the controls. The patients were divided into four groups: ARWO, ARWTO, NARWO and NARWTO. 40% (22/55) of AR and 33.3% (13/36) of NAR patients never complained of persistent nasal obstruction. Serum ECP levels were increased in the ARWO group. Serum total IgE was significantly elevated in the AR groups. MCA(1-Min) and MCA(1-T) were significantly reduced in the ARWO, ARWTO, and NARWO groups. NV(6-Min) and NV(6-T) were decreased in all PR groups, but only some of these differences were significant. In the ARWO group, MCA(2-Min) (r = -0.252), MCA(2-T) (r = -0.377), NV(6-Min) (r = -0.32), and NV(6-T) (r = -0.311) had significant relationships with serum ECP. We recommend acoustic rhinometry as a useful routine tool for the diagnosis of PR, even among patients without persistent subjective nasal obstruction. This technique might reveal the actual status of nasal congestion. An elevated serum ECP level might indicate severe AR and is negatively correlated with the results of acoustic rhinometry. PMID- 25135580 TI - The role of patient-mode high-resolution peripheral quantitative computed tomography indices in the prediction of failure strength of the elderly women's thoracic vertebral body. AB - The correlations between the failure load of 20 T12 vertebral bodies, their patient-mode high-resolution peripheral quantitative computed tomography (HR pQCT) indices, and the L1 areal bone mineral density (aBMD) were investigated. For the prediction of the T12 vertebral failure load, the T12 HR-pQCT microarchitectural parameters added significant information to that of L1 aBMD and to that of cortical BMD, but not to that of T12 vertebral BMD and not to that of T12 trabecular BMD. INTRODUCTION: HR-pQCT is a new in vivo imaging technique for assessing the three-dimensional microarchitecture of cortical and trabecular bone at the distal radius and tibia. But little is known about this technique in the direct measurement of vertebral body. METHODS: Twenty female donors with the mean age of 80.1 (7.6) years were included in the study. Dual X-ray absorptiometry of the lumbar spine and femur was performed. The spinal specimens (T11/T12/L1) were dissected, scanned using HR-pQCT scanner, and mechanically tested under 4 degrees wedge compression. The L1 aBMD, T12 patient-mode HR-pQCT indices, and T12 vertebral failure loads were analyzed. RESULTS: For the prediction of vertebral failure load, the inclusion of BV/TV into L1 aBMD was the best model (R (2) = 0.52), Tb.N and Tb.Sp added significant information to the L1 aBMD and to the cortical BMD, but none of the vertebral microarchitectural parameters yielded additional significant information to the trabecular BMD (or BV/TV) and to the vertebral BMD. CONCLUSION: Vertebral microarchitectural parameters obtained from the patient-mode HR-pQCT analysis provide significant information on bone strength complementary to that of aBMD and to that of cortical BMD, but not to that of vertebral BMD and not to that of trabecular BMD. PMID- 25135581 TI - Should Men and Women be Managed Differently in Glaucoma? AB - INTRODUCTION: To assess differences in associations of ocular perfusion pressure (OPP) as well as retinal and retrobulbar blood flow between men and women with primary open angle glaucoma (OAG). METHODS: A total of 116 patients with OAG (age 66.9 +/- 10.9 years, 70 females) participating in the Indianapolis Glaucoma Progression Study were assessed for OPP, retinal microcirculation, and retrobulbar blood flow. Confocal scanning laser Doppler flowmetry measured peripapillary retinal capillary blood flow. Color Doppler imaging measured peak systolic (PSV) and diastolic blood flow velocities and vascular resistance in the ophthalmic (OA), central retinal (CRA), and nasal and temporal short posterior ciliary arteries (N/T PCA). Bivariate Spearman correlation and multivariate linear regression analyses were performed. RESULTS: In female patients with OAG, inferior retinal capillary flow was associated with OPP (r = 0.246, P = 0.044). In men, superior and inferior sector retinal blood flow was associated with OPP (r = -0.402, P = 0.006 and r = -0.357, P = 0.016, respectively). There was no statistically significant association between OPP and retrobulbar blood vessel flow velocities in male patients with OAG but there was an association between OA and TPCA PSV and OPP in female patients with OAG (r = 0.290, P = 0.015 and r = 0.357, P = 0.002, respectively). In female patients with OAG, multivariate regression showed no statistically significant effect of any variable on the superior retinal capillary blood flow, with CRA PSV as a sole predictor to the inferior retinal sector (partial rho = 0.302, P = 0.015) and in male patients with OAG, superior sector retinal capillary blood flow was independently associated with intraocular pressure (partial rho = -0.371, P = 0.016) and OPP (partial rho = -0.456, P = 0.002) with a trend of association with OPP in the inferior retina (partial rho = -0.301, P = 0.053). CONCLUSIONS: There was a positive linear association between retinal microcirculation and OPP in females and a negative association in males. Male and female patients with OAG may differ in their vascular autoregulation in response to changes in OPP. PMID- 25135582 TI - Ophthalmic complications of dengue Fever: a systematic review. AB - INTRODUCTION: In recent years there has been a spurt of peer-reviewed publications on the ophthalmic complications of dengue fever. The authors aim to review the ocular manifestations, utility of relevant diagnostic tests, management, prognosis, and sequelae of dengue-related ocular complications. METHODS: A comprehensive literature search was conducted on Medline, PubMed, and Google Scholar databases. Only articles published or translated into the English language were considered, and key data from the full article of each paper was extracted and evaluated. RESULTS: The authors' search yielded 29 articles. A total of 686 patients with a mean age of 33.4 years (range 14-73 years) were included. Blurring of vision was the most common presenting symptom followed by scotoma. Ocular findings were mostly seen in the posterior pole of the fundus, manifesting as retinal hemorrhages, macular edema, foveolitis, vasculitis, and optic neuropathy. Most patients with dengue-related ophthalmic complications recover spontaneously without any treatment. Patients with severe visual loss or bilateral involvement were treated with systemic steroids and occasionally immunoglobulins. Prognosis of dengue-related ophthalmic complications is favorable; almost all patients had normal or showed improvement in visual acuity and complete resolution of dengue ophthalmic complications was noted in almost all cases. CONCLUSION: The pathological process of dengue ophthalmic complications is complex and clinical manifestations varied. Ophthalmic complications are usually seen in young adults who often present at the nadir of thrombocytopenia. Despite good recovery of vision and resolution of clinical signs in most patients, ophthalmologists and physicians should be aware and vigilant as isolated reports of cases of dengue ophthalmic complications with poor visual acuity refractory to treatment have been reported. PMID- 25135583 TI - Practical management of retinal vein occlusions. AB - Retinal vein occlusion (RVO) is the second most common cause of visual impairment due to retinal disease after diabetic retinopathy. Nowadays, the introduction of new, powerful diagnostic tools, such as spectral domain optical coherence tomography, and the widespread diffusion of intravitreal drugs, such as vascular endothelial grow factor inhibitors or implantable steroids, have dramatically changed the management and prognosis of RVO. The authors aim to summarize and review the main clinical, diagnostic, and therapeutic aspects of this condition. The authors conducted a review of the most relevant clinical trials and observational studies published within the last 30 years using a keyword search of MEDLINE, EMBASE, Current Contents, and Cochrane Library. Furthermore, for all treatments discussed, the level of evidence supporting its use, as per the US Preventive Task Force Ranking System, is provided. PMID- 25135584 TI - Multiple layers lens capsule true exfoliation in patient with primary angle closure glaucoma. AB - INTRODUCTION: True exfoliation of lens capsule is a relatively rare disorder that has a thin, fluttering membrane in the anterior chamber, mainly located in the pupil area, which is believed to have split from the anterior lens capsule. CASE REPORT: The authors present here a patient with true exfoliation and primary angle closure glaucoma in both eyes, the ultrastructure of one eye revealed that the delaminated membrane was composed of more than two layers in itself. CONCLUSION: Lens capsule true exfoliation could happen in patient with primary angle closure glaucoma, with more than two layers in itself. PMID- 25135585 TI - Topical isopropyl unoprostone for retinitis pigmentosa: microperimetric results of the phase 2 clinical study. AB - INTRODUCTION: The purpose of this study was to determine whether topical 0.15% isopropyl unoprostone (IU), a BK-channel activator, could improve or maintain the central retinal sensitivity in patients with middle- to late-stage retinitis pigmentosa (RP). IU was approved for glaucoma and ocular hypertension in 1994. The drug re-profiling strategy is one of the effective ways to develop safe drugs for patients with RP. METHODS: A randomized, double-blind, and placebo-controlled phase II safety/efficacy trial was conducted. One hundred and nine patients with middle- to late-stage RP having a visual acuity of >=0.5 were studied at six ophthalmological centers in Japan. The treatments of IU/day were divided into three groups: placebo group; two-drop group; and four-drop group for 24 weeks. The primary outcome measure was changes in the retinal sensitivity from baseline in the central 2 degrees determined by MP-1 microperimetry (MP-1, Nidek, Japan). The secondary outcomes were changes in best-correct visual acuity, contrast sensitivity, retinal sensitivity of the central 10 degrees by MP-1, mean deviation (MD) by a Humphrey field analyzer (HFA; Carl Zeiss Meditec, Dublin, CA, USA) 10-2, and the Visual Functioning Questionnaire 25 (VFQ-25) questionnaire scores. RESULTS: There was a tendency for a dose-dependent responsiveness in retinal sensitivity in the central 2 degrees , MD, and total VFQ-25 score after 24 weeks of IU instillation by a simple linear regression analysis. A stratified analysis showed a significant dose-dependent responsiveness of the 2 degrees central retinal sensitivity in more advanced patients (P = 0.028). The number of patients having a >=4 dB decrease in the primary outcome measure was significantly fewer in the four-drop group than in the placebo group (P = 0.02). No adverse reactions were observed. CONCLUSIONS: A higher dose of IU can delay progression of the central retinal sensitivity decrease through an improvement of retinal sensitivity. PMID- 25135586 TI - Effect of short-term oral valproic Acid on vision and visual field in retinitis pigmentosa. AB - INTRODUCTION: The aim of this study was to evaluate the effect of short-term oral valproic acid (VPA) on the vision and visual fields of patients with retinitis pigmentosa (RP). METHODS: In this prospective, nonrandomized trial, 10 patients (20 eyes) with established RP were treated with oral VPA 500 mg/day for 3 months. Visual acuity was monitored using the Snellen chart and values were converted into Early Treatment Diabetic Retinopathy Study chart and logarithm of the minimum angle of resolution (logMAR) equivalents. Visual field changes were evaluated using the Humphrey visual field analyzer (30-2 SITA standard test protocol). RESULTS: Mean visual acuity was significantly improved from a pretreatment value of 20/72 (logMAR 0.560 +/- 0.488) to 20/65 (logMAR 0.513 +/- 0.422) after 3 months of treatment (P = 0.006). Vision improved by at least one line or more than one line in 10 eyes, and remained stable in the other 10 eyes. Visual field improvement was noted in nine eyes (P < 0.05, chi(2) test), nine showing no significant field change and in two visual fields could not be recorded due to poor vision. CONCLUSION: Short-term (3-month) treatment with VPA improves the vision and visual field of patients with RP. PMID- 25135588 TI - Do We Currently Have Guidelines to Select an Adequate Prosthetic Valve to Surgically Treat Active Infective Endocarditis? AB - Active infective endocarditis is a devastating disease with high morbidity and mortality, which generally needs surgery and appropriate antimicrobial therapy. Selecting an adequate valve prosthesis is a central issue during surgery. This editorial discusses the recent literature available on this important topic. PMID- 25135587 TI - Ivabradine Versus Beta-Blockers in Patients with Conduction Abnormalities or Left Ventricular Dysfunction Undergoing Cardiac Surgery. AB - INTRODUCTION: In patients with conduction abnormalities or left ventricle (LV) dysfunction the use of beta-blockers for post cardiac surgery rhythm control is difficult and controversial, with a paucity of information about other drugs such ivabradine used postoperatively. The objective of this study was to compare the efficacy and safety of ivabradine versus metoprolol used perioperatively in cardiac surgery patients with conduction abnormalities or LV systolic dysfunction. METHODS: This was an open-label, randomized clinical trial enrolling 527 patients with conduction abnormalities or LV systolic dysfunction undergoing coronary artery bypass grafting or valvular replacement, randomized to take ivabradine or metoprolol, or metoprolol plus ivabradine. The primary endpoints were the composites of 30-day mortality, in-hospital atrial fibrillation (AF), in hospital three-degree atrioventricular block and need for pacing, in-hospital worsening heart failure (HF; safety endpoints), duration of hospital stay and immobilization and the above endpoint plus in-hospital bradycardia, gastrointestinal symptoms, sleep disturbances, cold extremities (efficacy plus safety endpoint). RESULTS: Heart rate reduction and prevention of postoperative AF or tachyarrhythmia with combined therapy was more effective than with metoprolol or ivabradine alone during the immediate postoperative management of cardiac surgery patients. In the Ivabradine group, the frequency of early postoperative pacing and HF worsening was smaller than in the Metoprolol group and in combined therapy group. The frequency of primary combined endpoint was lower in the combined Ivabradine + Metoprolol group compared with the monotherapy groups. CONCLUSION: Considering efficacy and safety, the cardiac rhythm reduction after open heart surgery in patients with conduction abnormalities or LV dysfunction with ivabradine plus metoprolol emerged as the best treatment in this trial. PMID- 25135589 TI - Aorta-to-Left Atrial Fistula Caused by Air Gun Pellet Cardiac Injury. AB - Abnormal communication between the ascending aorta and the cardiac chambers is rare, diverse in origin, and can be congenital or acquired. We report a case of a 10-year-old boy with acquired aorta-to-left atrial fistula associated with an air gun pellet injury and his successful treatment. PMID- 25135590 TI - Prognosis of Troponin-Positive Patients with Non-Obstructive Coronary Artery Disease. AB - INTRODUCTION: Troponin elevation is an independent risk factor for mortality, but the prognosis of patients with troponin elevation and non-obstructive coronary artery disease (CAD) is unknown. Recent data have suggested an increased risk of mortality. This study was performed to further investigate the outcomes of troponin-positive patients with obstructive and non-obstructive CAD. METHODS: A retrospective cohort analysis was performed of all patients with raised troponin presenting to Kettering General Hospital (January 2010 to December 2011, n = 1,351). The patients who had angiograms were stratified anatomically into obstructive CAD and non-obstructive CAD (<=50% stenosis). The obstructive CAD group (O-CAD) was sub-analyzed by management strategy: emergency re vascularization (<12 h), urgent, delayed, and medically managed. Patients with non-obstructive CAD were grouped by the cause of the raised troponin if this could be identified (NO-CAD-I) or cause remained unidentified (NO-CAD-U). The major adverse cardiac and cerebrovascular event (MACCE) and mortality rates were calculated at 30 days and 1-year follow-up. RESULTS: There was a preponderance of hypertension and severe renal impairment in the non-obstructive CAD group. The patients with NO-CAD-U were a low-risk group (MACCE at 1-year follow-up = 0). The remaining NO-CAD-I group had a similar risk to the O-CAD group for MACCE and mortality at 30 days and 1-year follow-up. In fact, at 1-year follow-up, the NO CAD-I patients when compared with the subgroups of O-CAD, had higher MACCE rates and mortality compared with the emergency re-vascularized group [MACCE: relative risk (RR) (95% CI) = 2.27 (1.29-3.40), P = 0.0047; mortality: RR (95% CI) = 2.08 (1.10-3.93), P = 0.024]. This was driven by higher risk non-cardiac death [RR (95% CI) = 4.10 (1.53-10.99), P = 0.005]. CONCLUSION: Patients with identified cause for raised troponin and non-obstructive CAD are at equivalent risk of MACCE and mortality at 30 days and 1-year follow-up compared to those with obstructive CAD. PMID- 25135591 TI - The Changing Role for Endomyocardial Biopsy in the Diagnosis of Giant-Cell Myocarditis. AB - Endomyocardial biopsy (EMB) is central to the diagnosis of giant-cell myocarditis (GCM) and planning further management. There is, however, no guideline-directed recommendation on re-biopsy or left ventricular EMB in a suspected case of acute, fulminant myocarditis following an indeterminate first biopsy. This manuscript illustrates, with a case, the changing role for EMB in the current era in the diagnosis of GCM. PMID- 25135592 TI - Perturbation of the interaction between Gal4p and Gal80p of the Saccharomyces cerevisiae GAL switch results in altered responses to galactose and glucose. AB - In S. cerevisiae, following the Whole Genome Duplication (WGD), GAL1-encoded galactokinase retained its signal transduction function but lost basal expression. On the other hand, its paralogue GAL3, lost kinase activity but retained its signalling function and basal expression, thus making it indispensable for the rapid induction of the S. cerevisiae GAL switch. However, a gal3Delta strain exhibits delayed growth kinetics due to the redundant signalling function of GAL1. The subfunctionalization between the paralogues GAL1 and GAL3 is due to expression divergence and is proposed to be due to the alteration in the Upstream Activating Sequences (UASG ). We demonstrate that the GAL switch becomes independent of GAL3 by altering the interaction between Gal4p and Gal80p without altering the configuration of UASG . In addition to the above, the altered switch of S. cerevisiae loses ultrasensitivity and stringent glucose repression. These changes caused an increase in fitness in the disaccharide melibiose at the expense of a decrease in fitness in galactose. The above altered features of the ScGAL switch are similar to the features of the GAL switch of K. lactis that diverged from S. cerevisiae before the WGD. PMID- 25135593 TI - Switching treatments in haemophilia: is there a risk of inhibitor development? AB - Patients with haemophilia A (and their physicians) may be reluctant to switch factor VIII (FVIII) concentrates, often due to concerns about increasing the risk of inhibitors; this reluctance to switch may contribute to patients missing the clinical benefits provided by the arrival of new factor VIII products. This topic was explored at the Eleventh Zurich Haemophilia Forum. Clinical scenarios for which product switching may be cause for concern were discussed; when there is a clinical need, there are no absolute contraindications to switching, but some patients (e.g. previously untreated patients and those undergoing elective surgery) may require more careful consideration. Both patient and physician surveys indicate that the reluctance to switch, and the fear of inhibitor development, does not appear to be evidence based. The evaluation of more recent data did not support previous studies suggesting that particular products (e.g. recombinant vs. plasma-derived and full length vs. B-domain modified) may be associated with increased risk. In addition, data from three national product switches showed that switching was not associated with increased inhibitor risk, but highlighted the need for regular inhibitor testing and for a centralised, unbiased database of inhibitor incidence. To conclude, current evidence does not suggest that switching products significantly influences inhibitor development. PMID- 25135594 TI - Do men need empowering too? A systematic review of entrepreneurial education and microenterprise development on health disparities among inner-city black male youth. AB - Economic strengthening through entrepreneurial and microenterprise development has been shown to mitigate poverty-based health disparities in developing countries. Yet, little is known regarding the impact of similar approaches on disadvantaged U.S. populations, particularly inner-city African-American male youth disproportionately affected by poverty, unemployment, and adverse health outcomes. A systematic literature review was conducted to guide programming and research in this area. Eligible studies were those published in English from 2003 to 2014 which evaluated an entrepreneurial and microenterprise initiative targeting inner-city youth, aged 15 to 24, and which did not exclude male participants. Peer-reviewed publications were identified from two electronic bibliographic databases. A manual search was conducted among web-based gray literature and registered trials not yet published. Among the 26 papers retrieved for review, six met the inclusion criteria and were retained for analysis. None of the 16 registered microenterprise trials were being conducted among disadvantaged populations in the U.S. The available literature suggests that entrepreneurial and microenterprise programs can positively impact youth's economic and psychosocial functioning and result in healthier decision-making. Young black men specifically benefited from increased autonomy, engagement, and risk avoidance. However, such programs are vastly underutilized among U.S. minority youth, and the current evidence is insufficiently descriptive or rigorous to draw definitive conclusions. Many programs described challenges in securing adequate resources, recruiting minority male youth, and sustaining community buy-in. There is an urgent need to increase implementation and evaluation efforts, using innovative and rigorous designs, to improve the low status of greater numbers of African-American male youth. PMID- 25135595 TI - Mycobacterium simiae infection in two unrelated patients with different forms of inherited IFN-gammaR2 deficiency. AB - Interferon-gamma receptor 2 (IFN-gammaR2) deficiency is a rare primary immunodeficiency characterized by predisposition to infections with weakly virulent mycobacteria, such as environmental mycobacteria and BCG vaccines. We describe here two children with IFN-gammaR2 deficiency, from unrelated, consanguineous kindreds of Arab and Israeli descent. The first patient was a boy who died at the age of 4.5 years, from recurrent, disseminated disease caused by Mycobacterium simiae. His IFN-gammaR2 defect was autosomal recessive and complete. The second patient was a girl with multiple disseminated mycobacterial infections, including infection with M. simiae. She died at the age of 5 years, a short time after the transplantation of umbilical cord blood cells from an unrelated donor. Her IFN-gammaR2 defect was autosomal recessive and partial. Autosomal recessive IFN-gammaR2 deficiency is life-threatening, even in its partial form, and genetic diagnosis and familial counseling are therefore particularly important for this condition. These two cases are the first of IFN gammaR2 deficiency associated with M. simiae infection to be described. PMID- 25135596 TI - Successful anti-TNF-alpha treatment in a girl with LAD-1 disease and autoimmune manifestations. AB - Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder, caused by the absence or reduced expression of the beta-2 integrins on granulocytes, and characterized by the inability of these cells to emigrate from the bloodstream towards the sites of tissue inflammation. A twelve-year-old girl with a diagnosis of LAD-1 syndrome and recurrent skin and mucosal infections since birth, presented with a two week history of fever, abdominal pain, vomiting, weight loss and polyarthralgia. She underwent an exploratory laparotomy with the finding of inflamed terminal ileum and colon and a normal appendix. Colonoscopy and videocapsule endoscopy showed multiple ileal and colonic mucosal ulcerations, which were compatible with inflammatory bowel disease, confirmed on histological examination. Given the lack of response to conventional therapy (prednisone and mesalamine), a monoclonal anti-TNF-alpha antibody was started at a dosage of 5 mg/kg at weeks 0,2,4,6 and then every 8 weeks. We observed a significant improvement of all clinical and laboratory parameters after the first weeks of therapy. Five months later, we anticipated the drug's administration every 5 weeks because of a precocious recurrence of symptoms. After 30 months of treatment no relapse nor any relevant side effects have been observed, and corticosteroids were withdrawn. Interestingly, our patient presented a small subset of CD18+ T cells, similarly to previously reported LAD-1 patients with mild phenotype, inflammatory bowel disease and CD18+ somatic revertant T cells. To the best of our knowledge, this is the first LAD-1 pediatric patient with inflammatory autoimmune complications who experienced a positive response to anti TNF-alpha treatment. PMID- 25135597 TI - Increased prevalence of gastrointestinal viruses and diminished secretory immunoglobulin a levels in antibody deficiencies. AB - PURPOSE: Gastrointestinal disease occurs frequently in antibody deficiencies. This study aims to explore the relation between gastrointestinal infections and mucosal homeostasis in patients with antibody deficiencies. METHODS: We performed an observational study including 54 pediatric antibody deficient patients (48 % CVID, 41 % CVID-like, 11 % XLA) and 66 healthy controls. Clinical symptom scores and stool samples were collected prospectively. Stool samples were evaluated for bacteria, parasites, viruses, secretory IgA- and for calprotectin levels. Results were compared between patients and controls. RESULTS: 24 % of antibody deficient patients versus 9 % of healthy controls tested positive for gastrointestinal viruses (p = 0.028). Fecal calprotectin levels were significantly higher in virus positive patients compared to virus negative patients (p = 0.002). However, in controls, fecal calprotectin levels were similar between virus positive and virus negative controls. Moreover, gastrointestinal virus positive patients had low serum IgA levels in 13/14 cases (94 %) versus 40/62 (62 %) patients in the virus negative patient group (p = 0.04). The virus positive patient group also displayed significantly lower secretory IgA levels in stool (median 13 ug/ml) than patients without gastrointestinal viruses detected or healthy controls (median 155 ug/ml) (p = 0.046). CONCLUSION: We here report an increased prevalence of gastrointestinal viruses and gastrointestinal complaints in antibody deficient patients. Patients that tested positive for gastrointestinal viruses showed diminished serum- and secretory IgA levels, and only in patients, virus positivity was associated with signs of mucosal inflammation. These findings suggest that particularly patients with low IgA are at risk for longstanding replication of gastrointestinal viruses, which may eventually result in CVID-related enteropathy. PMID- 25135598 TI - Sleep and circadian rhythms in hospitalized patients with decompensated cirrhosis: effect of light therapy. AB - Patients with liver cirrhosis often exhibit sleep-wake abnormalities, which are, at least to some extent, circadian in origin. A relatively novel non pharmacological approach to circadian disruption is appropriately timed bright light therapy. The aims of this pilot study were to investigate sleep-wake characteristics of a well-characterized population of inpatients with cirrhosis, and to evaluate the efficacy of bright light therapy in the hospital setting. Twelve consecutive inpatients with cirrhosis underwent complete sleep-wake assessment, to include qualitative and semi-quantitative (actigraphic) indices of night-time sleep quality, daytime sleepiness, diurnal preference, habitual sleep timing, quality of life, mood and circadian rhythmicity [i.e. urine collections for measurement of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s)]. Patients showed extremely impaired night sleep quality (Pittsburg Sleep Quality Index global score: 16.3 +/- 2.1) and daytime sleepiness was common (Epworth Sleepiness Scale: 8.3 +/- 3.2). Five patients were randomly assigned to a single room in which lighting was controlled in relation to timing, spectral composition and intensity (lights on at 06:30 and off at 22:30, blue-enriched, more intense light in the morning, red-enriched, less intense light in the afternoon/evening); the others stayed in identical rooms with standard lighting. Sleep diaries revealed poor sleep quality, prolonged sleep latency (67 +/- 138 min) and a reduced sleep efficiency (69 +/- 21%). These features were confirmed by actigraphy (sleep efficiency: 71 +/- 13%; fragmentation index: 55 +/- 15%). Quality of life was globally impaired, and mood moderately depressed (Beck Depression Inventory: 19.4 +/- 7.9). Seven patients underwent serial urine collections: no circadian aMT6s rhythm was detected in any of them, neither at baseline, nor during the course of hospitalization in either room (n = 4). In conclusion, sleep and circadian rhythms in hospitalized, decompensated patients with cirrhosis are extremely compromised. Treatment with bright light therapy did not show obvious, beneficial effects, most likely in relation to the severity of disturbance at baseline. PMID- 25135599 TI - Behavioral and neurochemical changes induced by repetitive combined treatments of ketamine and amphetamine in mice. AB - The combined abuse of recreational drugs such as ketamine (Ket) and amphetamine (Amph) should be seriously considered important social and health issues. Numerous studies have documented the behavioral and neurochemical changes associated with polydrug administration; however, most studies have only examined the acute effects. The consequences following chronic repetitive polydrug use are less studied. In the present study, intraperitoneal injections of saline, Amph (5 mg/kg), low dose Ket (LK, 10 mg/kg), high dose Ket (HK, 50 mg/kg), or Amph plus LK or HK (ALK or AHK) were conducted twice a day for three consecutive days, and one final treatment was administered on day 4. After seven total treatments, animal behaviors, including locomotion, stereotypy and ataxia, were examined in a novel open field. The expression of GAD67 and dopamine (DA) levels were assessed in the striatum and motor-related cortices using immunohistochemistry and high performance liquid chromatography. Drug-induced hyperactivities and Amph-mediated potentiation of Ket-triggered ataxia manifested after repeated drug treatments. A significant increase in the number of GAD67-positive puncta in the striatum and motor-related cortices was observed, suggesting a neural adaptive change in the GABAergic system. Four hours after the final treatment, while the behavioral hyperactivities had ceased, considerable changes were still evident in the motor related cortices, suggesting modulation to the DAergic system. Together, our results show the interactive effects of these two drugs in behavioral and neurochemical aspects and neural adaptive changes in the GABAergic and DAergic systems. PMID- 25135600 TI - CCN1 mutation is associated with atrial septal defect. AB - The genetic basis of congenital heart disease remains unknown in most of the cases. Recently, a novel mouse model shed new light on the role of CCN1/CYR61, a matricellular regulatory factor, in cardiac morphogenesis. In a candidate gene approach, we analyzed a cohort of 143 patients with atrial septal defects (ASD) by sequencing the coding exons of CCN1. In addition to three frequent polymorphisms, we identified an extremely rare novel heterozygous missense mutation (c.139C > T; p.R47W) in one patient with severe ASD. The mutation leads to an exchange of residues with quite different properties in a highly conserved position of the N-terminal insulin-like growth factor binding protein module. Further bioinformatic analysis, exclusion of known ASD disease genes as well as the exclusion of the mutation in a very high number of ethnically matched controls (more than 1,000 individuals) and in public genetic databases, indicates that the p.R47W variant is a probable disease-associated mutation. The report about ASD in mice in heterozygous Ccn 1 +/- animals strongly supports this notion. Our study is the first to suggest a relationship between a probable CCN1 mutation and ASD. Our purpose here was to draw attention to CCN1, a gene that we believe may be important for genetic analysis in patients with congenital heart disease. PMID- 25135601 TI - Incidence, predictors, and outcomes of extubation failure in children after orthotopic heart transplantation: a single-center experience. AB - The objective of this study is to describe the incidence, etiologies, predictors, and outcomes of extubation failure in children undergoing orthotopic heart transplantation (OHT). A Retrospective, observational study was designed to evaluate clinical outcomes. . The study was conducted in a cardiovascular intensive care unit (CVICU) setting at a single, tertiary care, academic children's hospital. We collected demographic, pre-operative, intra-operative, post-operative and peri-extubation data in a retrospective, observational format from patients who underwent OHT at our institution. Clinical outcomes evaluated included the success or failure of extubation, CVICU length of stay (LOS), hospital LOS, and in-hospital mortality. We utilized descriptive and univariate statistics to compare the group with extubation failure to the group with extubation success. There were no interventions in this study. During the study period, 127 patients qualified for inclusion. The median age of patients was 108 months [interquartile range (IQR): 25-169] and median weight was 23 kg (IQR: 10.6 48). Extubation failure occurred in 12.5 % (16/127) of the patients. Median duration of mechanical ventilation was 2 days (IQR: 1-4.5), median CVICU LOS was 7 days (IQR: 5-13), and the median hospital LOS was 36 days (IQR: 20-74). Overall in-hospital mortality was 2 % (2/127). There was a significant improvement in blood pressure (p < 0.001) with a decrease in inotropic score (p < 0.001) after removal of positive pressure ventilation among the patients with extubation success. Independent factors associated with extubation failure included lower body weight, need for mechanical ventilation prior to heart transplantation, renal failure prior to extubation attempt, and right ventricular diastolic dysfunction prior to extubation attempt. Our study demonstrates that extubation failure in patients after OHT is infrequent and the causes are diverse. Extubation success in children after OHT is associated with improvement in mean arterial blood pressure, decrease in inotropic support, and decrease in supplemental oxygen requirement. PMID- 25135602 TI - Impact of prenatal diagnosis in survivors of initial palliation of single ventricle heart disease: analysis of the National Pediatric Cardiology Quality Improvement Collaborative database. AB - Among infants with single ventricle congenital heart disease (SVD) requiring Stage I palliation (S1P), the impact of prenatal diagnosis (PD) on outcomes has been variably characterized. We investigated the impact of PD in a large multi center cohort of survivors of S1P in the National Pediatric Cardiology Quality Improvement Collaborative (NPCQIC) registry. Retrospective analysis of demographic and outcomes data among infants enrolled in the NPCQIC database; eligibility includes SVD requiring S1P and survival to discharge. From 43 contributing surgical centers, 591 infants had data available through time of BDG (519) or interstage death (55). Median gestational age was 39 weeks (31-46), and 66% had variants of hypoplastic left heart syndrome. PD was made in 445 (75%), with significant variation by center (p = 0.004). While infants with PD had slightly lower gestational age at birth (p < 0.001), there were no differences in birth weight, the presence of major syndromes or other organ system anomalies. Those without PD were more likely to have atrioventricular valve regurgitation (p = .002), ventricular dysfunction (p = 0.06), and pre-operative risk factors including acidosis (p < 0.001), renal insufficiency (p = 0.007), and shock (p = 0.05). Post-operative ventilation was shorter in the PD group (9 vs. 12 d, p = 0.002). Other early post-operative outcomes, interstage course, and outcomes at BDG were similar between groups. In a large cohort of infants with SVD surviving to hospital discharge after S1P, PD showed significant inter-site variation and was associated with improved pre-operative status and shorter duration of mechanical ventilation. The significance of such associations merits further study. PMID- 25135603 TI - Lifetime cardiac reinterventions following the Fontan procedure. AB - Patients with single ventricle physiology face significant morbidity and mortality following the Fontan procedure resulting in the need for additional cardiac reinterventions. Online patient education resources provide limited information on the reinterventions performed in single ventricle patients following the Fontan procedure. We sought to determine cardiac surgical and percutaneous reintervention rates and factors affecting reinterventions following the Fontan procedure. Databases from a single tertiary care center were retrospectively reviewed for all patients who underwent a Fontan procedure between 1978 and 2002. The number and type of cardiac surgical and percutaneous interventions following the Fontan procedure were determined, and relationships between need for reintervention and clinical variables were sought. A total of 91 patients (55 males) underwent the Fontan procedure at a median age of 5.50 years (IQR: 3.33-9.50 years). Median age at last follow-up, death, or transplant was 21.89 years (IQR: 10.87-25.51 years). Following the Fontan procedure, 60 (66%) patients required an additional 144 median sternotomies and 61 (67%) required 139 percutaneous cardiac interventions. Pacemaker system placement/replacement was the most common intervention following the Fontan procedure. The median time to first cardiac surgery following the Fontan was 1.96 years (IQR: 0.06-8.42 years) while the median time to the first percutaneous intervention was 7.63 years (IQR: 0.65-15.89 years). Families of single ventricle patients should be counseled on the likelihood of requiring additional cardiac interventions following the Fontan procedure. PMID- 25135604 TI - Predicting utility of exercise tests based on history/holter in patients with premature ventricular contractions. AB - Premature ventricular contractions (PVCs) are considered benign in patients with structurally normal hearts, particularly if they suppress with exercise. Catecholaminergic polymorphic ventricular tachycardia (CPVT) requires exercise testing to unmask the malignant phenotype. We studied risk factors and Holter monitor variables to help predict the necessity of exercise testing in patients with PVCs. We retrospectively reviewed 81 patients with PVCs that suppressed at peak exercise and structurally normal hearts referred to the exercise laboratory in 2011. We reviewed 11 patients from 2003 to 2012 whose PVCs were augmented at peak exercise (mean age 13 +/- 4 years; 52 % male, 180 exercise studies). We recorded clinical risk factors and comorbidities (family history of arrhythmia or sudden unexpected death [SUD], presence of syncope) and Holter testing parameters. Family history of VT or SUD (P = 0.011) and presence of VT on Holter (P = 0.011) were significant in predicting failure of PVCs to suppress at peak heart rate on exercise testing. Syncope was not statistically significant in predicting suppression (P = 0.18); however, CPVT was diagnosed in four patients with syncope during exercise. Quantity of PVCs, Lown grade, couplets on Holter, monomorphism, and PVC elimination at peak heart rate on Holter were not predictors of PVC suppression on exercise testing. Patients with syncope during exercise, family history of arrhythmia or SUD, or a Holter monitor showing VT warrant exercise testing to assess for CPVT. PMID- 25135605 TI - Next-generation sequencing is a credible strategy for blood group genotyping. AB - Although several medium/high-throughput tools have been engineered for molecular analysis of blood group genes, they usually rely on the targeting of single nucleotide polymorphisms, while other variants remain unidentified. To circumvent this limitation a strategy for genotyping blood group genes by next-generation sequencing (NGS) was set up. Libraries consisting of exons, flanking introns and untranslated regions of 18 genes involved in 15 blood systems were generated by the Ion AmpliSeq(TM) Library Kit 2.0 and by fragmenting polymerase chain reaction products, normalized by two different approaches, mixed and sequenced by the Ion Torrent Personal Genome Machine (PGM(TM) ) Sequencer. In our conditions, defined to limit both intra- and inter-sample variability, sequences from mixed libraries were read in a single run for a total coverage of 86.03% of the coding DNA sequences, including all loci defining the most clinically relevant antigens in all genes, except ABO. Importantly, the challenging attempt to generate gene specific data for the homologous genes was successful. This work, which combines two complementary approaches to generate libraries, defines technical conditions for genotyping blood group genes, illustrates that NGS is suitable for such an application and suggests that, after automation, this novel tool could be used for molecular typing at the laboratory level. PMID- 25135606 TI - Self-powered ion detectors based on dye-sensitized photovoltaics. AB - Autonomous sensing of metal ion contamination in remote environments with high reproducibility and sensitivity could unlock many new applications, but involves trade-offs between compactness, sensitivity, and power provisioning. In prior demonstrations of semi-autonomous sensors, the power source (e.g. a solar cell) was an additional component. Here, we demonstrate a concept, wherein a dye sensitized solar cell is used for both power generation and sensitive detection of ionic analytes, unlocking a new pathway for ultra-miniaturization and integration. PMID- 25135607 TI - Ovulation and extra-ovarian origin of ovarian cancer. AB - The mortality rate of ovarian cancer remains high due to late diagnosis and recurrence. A fundamental step toward improving detection and treatment of this lethal disease is to understand its origin. A growing number of studies have revealed that ovarian cancer can develop from multiple extra-ovarian origins, including fallopian tube, gastrointestinal tract, cervix and endometriosis. However, the mechanism leading to their ovarian localization is not understood. We utilized in vitro, ex vivo, and in vivo models to recapitulate the process of extra-ovarian malignant cells migrating to the ovaries and forming tumors. We provided experimental evidence to support that ovulation, by disrupting the ovarian surface epithelium and releasing chemokines/cytokines, promotes the migration and adhesion of malignant cells to the ovary. We identified the granulosa cell-secreted SDF-1 as a main chemoattractant that recruits malignant cells towards the ovary. Our findings revealed a potential molecular mechanism of how the extra-ovarian cells can be attracted by the ovary, migrate to and form tumors in the ovary. Our data also supports the association between increased ovulation and the risk of ovarian cancer. Understanding this association will lead us to the development of more specific markers for early detection and better prevention strategies. PMID- 25135608 TI - Screening carbohydrate libraries for protein interactions using the direct ESI-MS assay. Applications to libraries of unknown concentration. AB - A semiquantitative electrospray ionization mass spectrometry (ESI-MS) binding assay suitable for analyzing mixtures of oligosaccharides, at unknown concentrations, for interactions with target proteins is described. The assay relies on the differences in the ratio of the relative abundances of the ligand bound and free protein ions measured by ESI-MS at two or more initial protein concentrations to distinguish low affinity (<=10(3) M(-1)) ligands from moderate and high affinity (>10(5) M(-1)) ligands present in the library and to rank their affinities. Control experiments were performed on solutions of a single chain antibody and a mixture of synthetic oligosaccharides, with known affinities, in the absence and presence of a 40-component carbohydrate library to demonstrate the implementation and reliability of the assay. The application of the assay for screening natural libraries of carbohydrates against proteins is also demonstrated using mixtures of human milk oligosaccharides, isolated from breast milk, and fragments of a bacterial toxin and human galectin 3. PMID- 25135611 TI - Degradation mechanism of sulfonated poly(ether ether ketone) (SPEEK) ion exchange membranes under vanadium flow battery medium. AB - The degradation mechanism of hydrocarbon ion exchange membranes under vanadium flow battery (VFB) medium was investigated and clarified for the first time. This work will be highly beneficial for improving the chemical stability of hydrocarbon ion exchange membranes, which is one of the most challenging issues for VFB application. PMID- 25135609 TI - What protein charging (and supercharging) reveal about the mechanism of electrospray ionization. AB - Understanding the charging mechanism of electrospray ionization is central to overcoming shortcomings such as ion suppression or limited dynamic range, and explaining phenomena such as supercharging. Towards that end, we explore what accumulated observations reveal about the mechanism of electrospray. We introduce the idea of an intermediate region for electrospray ionization (and other ionization methods) to account for the facts that solution charge state distributions (CSDs) do not correlate with those observed by ESI-MS (the latter bear more charge) and that gas phase reactions can reduce, but not increase, the extent of charging. This region incorporates properties (e.g., basicities) intermediate between solution and gas phase. Assuming that droplet species polarize within the high electric field leads to equations describing ion emission resembling those from the equilibrium partitioning model. The equations predict many trends successfully, including CSD shifts to higher m/z for concentrated analytes and shifts to lower m/z for sprays employing smaller emitter opening diameters. From this view, a single mechanism can be formulated to explain how reagents that promote analyte charging ("supercharging") such as m NBA, sulfolane, and 3-nitrobenzonitrile increase analyte charge from "denaturing" and "native" solvent systems. It is suggested that additives' Bronsted basicities are inversely correlated to their ability to shift CSDs to lower m/z in positive ESI, as are Bronsted acidities for negative ESI. Because supercharging agents reduce an analyte's solution ionization, excess spray charge is bestowed on evaporating ions carrying fewer opposing charges. Bronsted basicity (or acidity) determines how much ESI charge is lost to the agent (unavailable to evaporating analyte). PMID- 25135610 TI - Peptide scrambling during collision-induced dissociation is influenced by N terminal residue basicity. AB - 'Bottom up' proteomic studies typically use tandem mass spectrometry data to infer peptide ion sequence, enabling identification of the protein whence they derive. The majority of such studies employ collision-induced dissociation (CID) to induce fragmentation of the peptide structure giving diagnostic b-, y-, and a- ions. Recently, rearrangement processes that result in scrambling of the original peptide sequence during CID have been reported for these ions. Such processes have the potential to adversely affect ion accounting (and thus scores from automated search algorithms) in tandem mass spectra, and in extreme cases could lead to false peptide identification. Here, analysis of peptide species produced by Lys-N proteolysis of standard proteins is performed and sequences that exhibit such rearrangement processes identified. The effect of increasing the gas-phase basicity of the N-terminal lysine residue through derivatization to homoarginine toward such sequence scrambling is then assessed. The presence of a highly basic homoarginine (or arginine) residue at the N-terminus is found to disfavor/inhibit sequence scrambling with a coincident increase in the formation of b(n-1)+H(2)O product ions. Finally, further analysis of a sequence produced by Lys-C proteolysis provides evidence toward a potential mechanism for the apparent inhibition of sequence scrambling during resonance excitation CID. PMID- 25135612 TI - Assessment of motor and process skills in daily life activities of treated substance addicts. AB - AIM: The purpose of this study was to apply the Assessment of Motor and Process Skills (AMPS) in a sample of people in treatment for addictive behaviours and to study the results. METHODS: The test was applied to a sample of 101 outpatients in treatment for addiction to substances. The results were studied in relation to gender, age, level of education, and variables related to addiction. RESULTS: Motor and cognitive performance was negatively related to time of addiction and its severity. Sixty per cent of the sample reached suboptimal scores and 25% showed scores suggesting significant deterioration, especially with regard to cognitive processing skills. CONCLUSIONS: The AMPS seems to be a useful instrument to estimate the cognitive and motor impairment associated with addiction in daily life activities. The present work is the first to consider its applicability to drug users under treatment. The percentage of subjects affected and the magnitude of the observed impairment in the sample suggest the need to consider taking these deficits into account in treatment programmes and the convenience of incorporating functional rehabilitation as a basic element of the treatment of persons with addictions. Future studies should develop this instrument in larger samples, increasing the representativeness and generalizability of the results. PMID- 25135614 TI - Seasonal variation in the presentation of thyroid cancer in the USA: an analysis of the Surveillance, Epidemiology and End Results Registry. PMID- 25135613 TI - A binuclear Zn(II)-Zn(II) complex from a 2-hydroxybenzohydrazide-derived Schiff base for selective detection of pyrophosphate. AB - A hydroxybenzohydrazide-based Schiff base ligand was conveniently synthesized. Upon addition of Zn(2+) cations, the ligand exhibited a high tendency to form a binuclear structure with a 2 : 2 ligand-to-zinc ratio, which was accompanied by a large fluorescence turn-on (lambdaem = 507 nm, phifl~ 0.28). The reactivity of the zinc complex was examined using different phosphate anions, which reveals a higher response to acid pyrophosphate anions. Detailed spectroscopic studies show that the pyrophosphate response is based on the ligand displacement mechanism. PMID- 25135615 TI - Long-term use of 5alpha-reductase inhibitors and the risk of male breast cancer. AB - BACKGROUND: The 5alpha-reductase inhibitors (5-ARI) finasteride and dutasteride are indicated for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. Case reports have suggested that 5-ARIs increase the risk for male breast cancer, with no conclusive evidence. The objective of this study was to quantify the association between use of 5-ARIs and the risk for male breast cancer. METHODS: A case-control study was conducted with data from the United Kingdom Clinical Practice Research Datalink database among all men aged 45 years and older in the period 1 January 1992 to 31 December 2011. Cases of men diagnosed with breast cancer were matched to up 10 controls on age and general practice. Crude and adjusted odds ratios were estimated for the risk of breast cancer associated with the use of 5-ARIs. RESULTS: Three hundred and ninety-eight cases were identified and matched to 3,930 controls. Ever use of 5-ARIs was associated with an adjusted odds ratio for breast cancer of 1.08 (95 % CI 0.62 1.87) compared to non-users. Increasing cumulative duration of treatment showed no increasing risks: adjusted odds ratios for use for less than 280, for 280 to 1,036 and for more than 1,036 days were 1.21 (95 % CI 0.47-3.10), 0.94 (95 % CI 0.36-2.41) and 1.29 (95 % CI 0.54-3.08), respectively. CONCLUSIONS: In this study, there was no evidence of an association between short- or long-term treatment with 5-ARIs and the risk for breast cancer in older men. PMID- 25135616 TI - The presence of clustered circulating tumor cells (CTCs) and circulating cytokines define an aggressive phenotype in metastatic colorectal cancer. AB - PURPOSE: Colon carcinoma is a malignant tumor showing a marked preference to metastasize to distant organs. The presence of circulating tumor cells (CTCs) in the peripheral blood is a prerequisite for the formation of distant metastases. However, whether circulating cytokines are linked to the circulation of tumor cells, as individual cells or clusters, remain unclear. In this study, we investigated the circulating levels of TGF-beta, CXCL1, VEGF and PAI-1 as potential bioindicators of the presence of CTCs in patients with metastatic colon cancer. METHODS: Circulating tumor cells (CTCs) were isolated from peripheral blood by immunomagnetic separation and phenotypically characterized in a cohort of 103 patients with metastatic colon cancer. TGF-beta, CXCL1, VEGF and PAI-1 concentrations were determined by immunoassay in plasma samples from the same patients. RESULTS: We detected two different populations of CTCs, single cells or clusters in patients with metastatic colon cancer. Importantly, we found that the presence of clustered CTCs is significantly associated with elevated circulating levels of TGF-beta and CXCL1 and with reduced overall survival. Finally, we observed that circulating levels of cytokines are differently associated with the two populations of CTCs. CONCLUSIONS: Taken together, these findings show that detection of clustered CTCs represents a negative prognostic factor in patients with metastatic colon cancer. The presence of clustered CTCs is associated with elevated circulating levels of cytokines such as TGF-beta and CXCL1. This suggests an additional role for circulating cytokines as predictive tool for cancer prognosis and diagnosis of minimal residual disease as well as assessment of tumor sensitivity to anticancer therapy. PMID- 25135618 TI - Indications, technique, and outcome of therapeutic apheresis in European pediatric nephrology units. AB - BACKGROUND: Few observations on apheresis in pediatric nephrology units have been published. METHODS: This retrospective study involved children <=18 years undergoing plasma exchange (PE), immunoadsorption (IA), or double filtration plasmapheresis (DFPP) in 12 European pediatric nephrology units during 2012. RESULTS: Sixty-seven children underwent PE, ten IA, and three DFPP, for a total of 738 PE and 349 IA/DFPP sessions; 67.2 % of PE and 69.2 % of IA/DFPP patients were treated for renal diseases, in particular focal segmental glomerulosclerosis (FSGS), hemolytic-uremic syndrome (HUS), and human leukocyte antigen (HLA) desensitization prior to renal transplantation; 20.9 % of PE and 23.1 % of IA/DFPP patients had neurological diseases. Membrane filtration was the most common technique, albumin the most frequently used substitution fluid, and heparin the preferred anticoagulant. PE achieved full disease remission in 25 patients (37.3 %), partial remission in 22 (32.8 %), and had no effect in 20 (29.9 %). The response to IA/DFPP was complete in seven patients (53.8 %), partial in five (38.5 %), and absent in one (7.7 %). Minor adverse events occurred during 6.9 % of PE and 9.7 % of IA/DFPP sessions. CONCLUSIONS: PE, IA, and DFPP are safe apheresis methods in children. Efficacy is high in pediatric patients with recurrent focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (HUS), human leukocyte antigen (HLA) sensitization, and neurological autoimmune diseases. PMID- 25135620 TI - Crystal lattice effect on the quenching of the intracluster magnetic interaction in [V12B18O60H6](10-) polyoxometalate. AB - In the present work, the synthesis and structural characterization of four new polyoxovanadoborate (BVO) frameworks based on the [V12B18O60H6](10-) polyanion are reported: (NH4)8(1,3-diapH2)[V12B18O60H6].5H2O (1), K8(NH4)2[V12B18O60H6].18H2O (2), K10[V12B18O60H6].10H2O (3) and K8Cs2[V12B18O60H6].10H2O (4). A global antiferromagnetic behaviour is observed for these 10V(IV)/2V(V) mixed valence clusters. The magnetic data of 1, 2 and 3, which present different countercation environments, show that 1 is more coupled than 2 and 3. DFT calculations show that the positive charges strongly influence the polarization mechanism of the spin density of the vanadyl groups and the extent of the magnetic orbitals, therefore corroborating the experimental observation of the quenching effect of the magnetic coupling between vanadium centres of 2 and 3. PMID- 25135619 TI - Can vitamin D status be assessed by serum 25OHD in children? AB - BACKGROUND: To examine the relationship of serum 25-hydroxyvitamin D (25OHD) concentrations with serum parathyroid hormone (PTH) levels, body mass index (BMI), and environmental factors in a population of Caucasian children living at latitude 43 degrees N. METHODS: Cross-sectional study on 288 children aged 1 month to 13 years who presented to a pediatric emergency unit during a 21-month period. RESULTS: Mean (SD) serum 25OHD concentrations were 40.6 (17.6), 30.9 (12.0), and 26.4 (9.9) ng/ml (1 ng/ml = 2.5 nmol/l), in children aged 0-1, 2-5, and >= 6 years, respectively. Serum PTH levels were 26.6 (13.6), 24.3 (11.9), and 32.7 (12.1) pg/ml in the same groups. Infants had 25OHD concentrations significantly higher. PTH levels were significantly higher in children aged >= 6 years. There was no significant correlation between serum 25OHD and PTH concentrations. Totals of 15.6 % and 2.1 % of children had 25OHD values less than 20 and 10 ng/ml, respectively, but none had elevated serum PTH or clinical manifestations related with vitamin D deficiency. Age (inverse correlation) and season (higher values in summer), but not BMI, sex, and time spent outdoors, influenced serum 25OHD concentrations. CONCLUSIONS: Our results raise doubt on the assumption of only a serum 25OHD threshold as indicative of vitamin D deficiency in children. PMID- 25135617 TI - Cardiac CT for myocardial ischaemia detection and characterization--comparative analysis. AB - The assessment of patients presenting with symptoms of myocardial ischaemia remains one of the most common and challenging clinical scenarios faced by physicians. Current imaging modalities are capable of three-dimensional, functional and anatomical views of the heart and as such offer a unique contribution to understanding and managing the pathology involved. Evidence has accumulated that visual anatomical coronary evaluation does not adequately predict haemodynamic relevance and should be complemented by physiological evaluation, highlighting the importance of functional assessment. Technical advances in CT technology over the past decade have progressively moved cardiac CT imaging into the clinical workflow. In addition to anatomical evaluation, cardiac CT is capable of providing myocardial perfusion parameters. A variety of CT techniques can be used to assess the myocardial perfusion. The single energy first-pass CT and dual energy first-pass CT allow static assessment of myocardial blood pool. Dynamic cardiac CT imaging allows quantification of myocardial perfusion through time-resolved attenuation data. CT-based myocardial perfusion imaging (MPI) is showing promising diagnostic accuracy compared with the current reference modalities. The aim of this review is to present currently available myocardial perfusion techniques with a focus on CT imaging in light of recent clinical investigations. This article provides a comprehensive overview of currently available CT approaches of static and dynamic MPI and presents the results of corresponding clinical trials. PMID- 25135622 TI - Effects of four additive solutions on canine leukoreduced red cell concentrate quality during storage. AB - BACKGROUND: Additive solutions (AS) and prestorage leukoreduction (LR) are important tools used to maintain erythrocyte viability during storage and avoid transfusion reactions in recipients, respectively. OBJECTIVES: The purpose of the study was to determine the efficacy of a WBC filter (Immugard IIIRC) and compare the effect of 4 AS (phosphate-adenine-glucose-guanosine-gluconate-mannitol [PAGGGM], saline-adenine-glucose-mannitol [SAGM], Adsol, Optisol) on the in vitro quality of canine leukoreduced packed RBC units (pRBC) stored for 41 days. METHODS: Five hundred milliliters of blood were collected from 8 healthy dogs each into 70 mL of citrate-phosphate-dextrose (CPD) solution, and were leukoreduced by a polyurethane filter. pRBC of each dog were divided equally into 4 bags containing a different AS. Bags were stored for 41 days at 4 degrees C and evaluated every 10 days. Variables analyzed included pH, PCV, and% hemolysis, and lactate, glucose, potassium, sodium, ATP, and 2,3-diphosphoglycerate (2,3-DPG) concentrations. RESULTS: The LR resulted in residual WBC counts comparable to human standards. During storage, pH, and glucose, 2,3-DPG, and ATP concentrations decreased, and hemolysis, and lactate, sodium, and potassium concentrations increased (P < .05). Significant differences between AS were seen in the glucose and sodium concentrations, due to the composition of AS. Also, the pH maintained by PAGGGM at day 21 was significantly higher than that seen with SAGM or Adsol. CONCLUSIONS: All AS used gave satisfactory results during the first 21 days of storage based on the degree of hemolysis, and on ATP and 2,3-DPG concentrations. When compared with day 1 values, significant changes were seen in these variables by day 31 with all AS. PMID- 25135621 TI - Critical periods of increased fetal vulnerability to a maternal high fat diet. AB - BACKGROUND: Fetal adaptations to high fat (HF) diet in utero (IU) that may predispose to Metabolic Syndrome (MetS) in adulthood include changes in fetal hepatic gene expression. Studies were performed to determine whether maternal exposure to HF diet at different stages during pregnancy had different effects on the fetus, including hepatic gene expression. METHODS: Female wild type mice were fed either a HF or breeding chow (C) for 2 wks prior to mating. The experimental groups were composed of embryonic day (e) 18.5 fetuses obtained from WT female mice that were fed HF (HF, 35.5% fat) or breeding chow (C, 9.5% fat) for 2 wk before mating until e9.5 of pregnancy (periconception-midpregnancy). At e9.5 dams were switched to the opposite diet (C-HF or HF-C). RESULTS: Exposure to HF diet throughout pregnancy reduced maternal weight gain compared to C diet (p < 0.02 HF vs. C). HF-C dams had significantly decreased adiponectin levels and litter size when compared to C-HF (p < 0.02 HF-C vs C-HF). Independent of the timing of exposure to HF, fetal weight and length were significantly decreased when compared to C diet (HF, C-HF and HF-C vs. C p < 0.02). HF diet during the second half of pregnancy increased expression of genes in the fetal liver associated with fetal growth (C-HF vs C p < 0.001), glucose production (C-HF vs C p < 0.04), oxidative stress and inflammation (C-HF vs C p < 0.01) compared to C diet. CONCLUSIONS: This model defines that there are critical periods during gestation in which the fetus is actively shaped by the environment. Early exposure to a HF diet determines litter size while exposure to HF during the second half of pregnancy leads to dysregulation of expression of key genes responsible for fetal growth, hepatic glucose production and oxidative stress. These findings underscore the importance of future studies designed to clarify how these critical periods may influence future risk of developing MetS later in life. PMID- 25135624 TI - MicroRNAs: a new key in lung cancer. AB - Lung cancer as a malignance has been killing numerous patients around the world annually, and small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are the two major types, the later accounting for nearly 80 % of lung cancer. There are multiple causes for lung cancer, and more researches have been carried out to prevent, anticipate, and diagnose the cancer. MicroRNAs (miRNAs) are small non-coding RNA molecules capable of regulating expression of over 50 % of protein-coding genes. The RNA molecules are stable in tissues and blood, so it can tend to be a biomarker in anti-lung cancer. Here, this is a review on the roles of miRNAs for possible ways to prevent lung cancer in clinical trials. PMID- 25135623 TI - Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small cell lung cancer. AB - The revolution in individualized therapy for patients with advanced non-small cell lung cancer (NSCLC) has seen the emergence of a number of molecularly targeted therapies for distinct patient molecular subgroups. Activating anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3-7 % of NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for patients with tumors harboring this event. However, resistance to ALK-targeted therapies is a ubiquitous problem in the management of advanced ALK-positive NSCLC and can be mediated by secondary kinase mutations or the activation of compensatory alternative oncogenic drivers. New, more potent ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802), and AP26113 are now emerging, together with an increased knowledge of the molecular basis of resistance. There is a need to evaluate the optimal clinical application of these new agents, either as sequential therapies or in combination with other targeted agents, to combat resistance and prolong survival in patients with ALK-positive NSCLC. The remarkable clinical activity of ALK inhibitors also emphasizes the importance of optimal diagnostic testing algorithms, to ensure that all eligible patients receive these breakthrough therapies. PMID- 25135628 TI - Photoinduced oxidation of water in the pyridine-water complex: comparison of the singlet and triplet photochemistries. AB - It has recently been shown that low-lying dark charge-separated singlet excited states of npi* and pipi* character exist in the hydrogen-bonded pyridine-water complex in addition to the familiar npi* and pipi* excited states of the pyridine chromophore. The former have been shown to promote the transfer of a proton from water to pyridine, resulting in the pyridinyl-hydroxyl radical pair. In the present work, the potential-energy surfaces of the triplet excited states of the pyridine-water complex have been explored with the same ab initio electronic structure methods (ADC(2), CASPT2). Minimum-energy reaction paths for excited state H atom transfer, energy surfaces in the vicinity of the barrier for H atom transfer, as well as multistate surface crossings have been characterized. The photochemical reaction mechanisms on the singlet and triplet potential-energy surfaces are compared, and their relevance for photoinduced water oxidation with the pyridine chromophore are discussed. PMID- 25135626 TI - Benzoic and sorbic acid in soft drink, milk, ketchup sauce and bread by dispersive liquid-liquid microextraction coupled with HPLC. AB - Benzoic acid and sorbic acid are widely used for food preservation. These preservatives are generally recognised as safe. The aim of this study was to determine the level of benzoic and sorbic acid in food samples that are usually consumed in Iran. Therefore, 54 samples, including 15 soft drinks, 15 ultra-high temperature milk, 15 ketchup sauces and 9 bread samples, were analysed by high performance liquid chromatography with UV detection. Benzoic acid was detected in 50 (92.5%) of the samples ranging from 3.5 to 1520 ug mL-1, while sorbic acid was detected in 29 (50.3%) samples in a range of 0.8 and 2305 ug mL-1. Limits of detection and limits of quantification for benzoate were found to be 0.1 and 0.5 ug mL-1, respectively, and for sorbate 0.08 and 0.3 ug mL-1, respectively. The results showed that benzoic acid and sorbic acid widely occur in food products in Iran. PMID- 25135629 TI - Adaptive processes drive ecomorphological convergent evolution in antwrens (Thamnophilidae). AB - Phylogenetic niche conservatism (PNC) and convergence are contrasting evolutionary patterns that describe phenotypic similarity across independent lineages. Assessing whether and how adaptive processes give origin to these patterns represent a fundamental step toward understanding phenotypic evolution. Phylogenetic model-based approaches offer the opportunity not only to distinguish between PNC and convergence, but also to determine the extent that adaptive processes explain phenotypic similarity. The Myrmotherula complex in the Neotropical family Thamnophilidae is a polyphyletic group of sexually dimorphic small insectivorous forest birds that are relatively homogeneous in size and shape. Here, we integrate a comprehensive species-level molecular phylogeny of the Myrmotherula complex with morphometric and ecological data within a comparative framework to test whether phenotypic similarity is described by a pattern of PNC or convergence, and to identify evolutionary mechanisms underlying body size and shape evolution. We show that antwrens in the Myrmotherula complex represent distantly related clades that exhibit adaptive convergent evolution in body size and divergent evolution in body shape. Phenotypic similarity in the group is primarily driven by their tendency to converge toward smaller body sizes. Differences in body size and shape across lineages are associated to ecological and behavioral factors. PMID- 25135630 TI - Low-risk transfusion-related acute lung injury donor strategies and the impact on the onset of transfusion-related acute lung injury: a meta-analysis. AB - BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. In the past decade blood banks have implemented low-risk TRALI donor strategies, including a male-only donor policy for plasma containing blood products to prevent onset of TRALI. We performed a meta-analysis to determine whether use of low-risk TRALI donor strategies for plasma indeed reduces onset of TRALI. STUDY DESIGN AND METHODS: We searched MEDLINE and Cochrane Central Register of Controlled Trials from January 1995 up to January 2013. Two reviewers independently extracted data on study characteristics, methods, and outcomes. Primary endpoint was onset of TRALI. Subgroup analyses were performed for patient populations prone to develop TRALI and general patient populations. RESULTS: Ten articles were included. Meta-analysis using a random effects model taking into account all transfused products showed a significant reduction for the risk of TRALI after implementation of low-risk TRALI donor strategies (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42-0.88). Data from patient populations prone to develop TRALI showed a significant reduction of TRALI risk (OR, 0.51; 95% CI, 0.29-0.90), while data from general patient populations showed a similar nonsignificant trend (OR, 0.66; 95% CI, 0.40-1.09). Results were similar when taking only plasma products into account (OR, 0.62; 95% CI, 0.42-0.92). CONCLUSION: The introduction of low-risk TRALI donor strategies for plasma-containing products results in a reduction of TRALI. PMID- 25135631 TI - Sodium tanshinone IIA sulfonate attenuates radiation-induced fibrosis damage in cardiac fibroblasts. AB - The main pathological change in radiation-induced heart disease is fibrosis. Emerging evidence has indicated that sodium tanshinone IIA sulfonate (STS) was used for treating fibrosis diseases. The present study was undertaken to characterize the effect of STS on radiation-induced cardiac fibrosis (RICF) on cultured cardiac fibroblasts (CFs). CFs were irradiated with 1 or 2 Gy X-rays, and the expression of TGF-beta1 and collagen I (Col-1) increased, indicating that low-dose X-rays promoted fibrosis damage effect. The fibrosis damage was accompanied by morphologic changes in the endoplasmic reticulum (ER), as well as an increase in the expression of the ER stress-related molecules, GRP78 and CHOP. Administration of STS reduced ROS production and decreased the expression of Col 1, TGF-beta1, p-Smad2/3, GRP78, and CHOP in irradiated CFs, thus weakening the radiation-induced fibrosis damage and ER stress. Radiation-induced fibrosis damage was observed on a cellular level. The involvement of ER stress in radiation-induced fibrosis damage was demonstrated for the first time. STS attenuated the fibrosis damage effect in CFs and this effect may be related to its antioxidant action, and also related to its inhibition of ER stress and TGF beta1-Smad pathway. These results suggest that STS shows a good prospect in clinical prevention and treatment of RICF. PMID- 25135627 TI - Dendritic cell subsets require cis-activation for cytotoxic CD8 T-cell induction. AB - Dendritic cells (DCs) are required for the induction of cytotoxic T cells (CTL). In most tissues, including the lung, the resident DCs fall into two types expressing the integrin markers CD103 and CD11b. The current supposition is that DC function is predetermined by lineage, designating the CD103(+) DC as the major cross-presenting DC able to induce CTL. Here we show that Poly I:C (TLR3 agonist) or R848 (TLR7 agonist) do not activate all endogenous DCs. CD11b(+) DCs can orchestrate a CTL response in vivo in the presence of a TLR7 agonist but not a TLR3 agonist, whereas CD103(+) DCs require ligation of TLR3 for this purpose. This selectivity does not extend to antigen cross-presentation for T-cell proliferation but is required for induction of cytotoxicity. Thus, we demonstrate that the ability of DCs to induce functional CTLs is specific to the nature of the pathogen-associated molecular pattern (PAMP) encountered by endogenous DC. PMID- 25135632 TI - ApiCOWplexa 2013--2nd International Meeting on Apicomplexan Parasites in Farm Animals. PMID- 25135633 TI - Elevated dopamine in the medial prefrontal cortex suppresses cocaine seeking via D1 receptor overstimulation. AB - Previous investigations indicate that the dopamine-beta-hydroxylase (DBH) inhibitors disulfiram and nepicastat suppress cocaine-primed reinstatement of cocaine self-administration behaviour. Moreover, both inhibitors increase dopamine release in the rat medial prefrontal cortex (mPFC) and markedly potentiate cocaine-induced dopamine release in this region. This study was aimed to clarify if the suppressant effect of DBH inhibitors on cocaine reinstatement was mediated by the high extracellular dopamine in the rat mPFC leading to a supra-maximal stimulation of D1 receptors in the dorsal division of mPFC, an area critical for reinstatement of cocaine-seeking behaviour. In line with previous microdialysis studies in drug-naive animals, both DBH inhibitors potentiated cocaine-induced dopamine release in the mPFC, in the same animals in which they also suppressed reinstatement of cocaine seeking. Similar to the DBH inhibitors, L-DOPA potentiated cocaine-induced dopamine release in the mPFC and suppressed cocaine-induced reinstatement of cocaine-seeking behaviour. The bilateral microinfusion of the D1 receptor antagonist SCH 23390 into the dorsal mPFC not only prevented cocaine-induced reinstatement of cocaine seeking but also reverted both disulfiram- and L-DOPA-induced suppression of reinstatement. Moreover, the bilateral microinfusion of the D1 receptor agonist chloro-APB (SKF 82958) into the dorsal mPFC markedly attenuated cocaine-induced reinstatement of cocaine seeking. These results suggest that stimulation of D1 receptors in the dorsal mPFC plays a crucial role in cocaine-induced reinstatement of cocaine seeking, whereas the suppressant effect of DBH inhibitors and L-DOPA on drug-induced reinstatement is mediated by a supra-maximal stimulation of D1 receptors leading to their inactivation. PMID- 25135634 TI - Japanese guidelines of the management of hematuria 2013. PMID- 25135635 TI - Blood pressure control and satisfaction of hypertensive patients following a switch to combined drugs of an angiotensin receptor blocker and a calcium channel blocker in clinical practice of nephrology. AB - BACKGROUND: Combination drugs containing an angiotensin receptor blocker and a calcium channel blocker have been widely commercialized in recent years, and their advantages, such as improvements in adherence, and reductions in medication costs, have been greatly emphasized. However, the actual situations and the impact of switching to combination drugs in clinical practice of nephrology are not fully understood. METHODS: This study was conducted in outpatients of nephrology who received antihypertensive medicines, and who switched to combination drugs. Changes in the potency of the antihypertensive drugs, and blood pressure were examined retrospectively before and after changing treatments. In addition, the study also involved patients' questionnaire, which examined changes in blood pressure at home, the presence or absence of missed doses, the impact on medication-related expenses, and the level of patients' satisfaction with regard to combination drugs. RESULTS: Survey results from 90 participants revealed that changing to combination drugs resulted in a reduction of missed doses, a decrease in blood pressure measured in an outpatient setting, and a reduction in medication-related expenses in total patients, non-chronic kidney disease (CKD) patients, and CKD patients. CONCLUSION: Our study shows that switching to combination antihypertensive drugs resulted in an improvement in adherence and a reduction in medication-related expenses, and revealed that patient satisfaction was high. Combination drugs for hypertensive patients may be beneficial in both medical and economical viewpoints. PMID- 25135636 TI - Evolutionarily conserved roles of the dicer helicase domain in regulating RNA interference processing. AB - The enzyme Dicer generates 21-25 nucleotide RNAs that target specific mRNAs for silencing during RNA interference and related pathways. Although their active sites and RNA binding regions are functionally conserved, the helicase domains have distinct activities in the context of different Dicer enzymes. To examine the evolutionary origins of Dicer helicase functions, we investigated two related Dicer enzymes from the thermophilic fungus Sporotrichum thermophile. RNA cleavage assays showed that S. thermophile Dicer-1 (StDicer-1) can process hairpin precursor microRNAs, whereas StDicer-2 can only cleave linear double-stranded RNAs. Furthermore, only StDicer-2 possesses robust ATP hydrolytic activity in the presence of double-stranded RNA. Deletion of the StDicer-2 helicase domain increases both StDicer-2 cleavage activity and affinity for hairpin RNA. Notably, both StDicer-1 and StDicer-2 could complement the distantly related yeast Schizosaccharomyces pombe lacking its endogenous Dicer gene but only in their full-length forms, underscoring the importance of the helicase domain. These results suggest an in vivo regulatory function for the helicase domain that may be conserved from fungi to humans. PMID- 25135638 TI - Irreversible heavy chain transfer to chondroitin. AB - We have recently demonstrated that the transfer of heavy chains (HCs) from inter alpha-inhibitor, via the enzyme TSG-6 (tumor necrosis factor-stimulated gene 6), to hyaluronan (HA) oligosaccharides is an irreversible event in which subsequent swapping of HCs between HA molecules does not occur. We now describe our results of HC transfer experiments to chondroitin sulfate A, chemically desulfated chondroitin, chemoenzymatically synthesized chondroitin, unsulfated heparosan, heparan sulfate, and alginate. Of these potential HC acceptors, only chemically desulfated chondroitin and chemoenzymatically synthesized chondroitin were HC acceptors. The kinetics of HC transfer to chondroitin was similar to HA. At earlier time points, HCs were more widely distributed among the different sizes of chondroitin chains. As time progressed, the HCs migrated to lower molecular weight chains of chondroitin. Our interpretation is that TSG-6 swaps the HCs from the larger, reversible sites on chondroitin chains, which function as HC acceptors, onto smaller chondroitin chains, which function as irreversible HC acceptors. HCs transferred to smaller chondroitin chains were unable to be swapped off the smaller chondroitin chains and transferred to HA. HCs transferred to high molecular weight HA were unable to be swapped onto chondroitin. We also present data that although chondroitin was a HC acceptor, HA was the preferred acceptor when chondroitin and HA were in the same reaction mixture. PMID- 25135637 TI - The cellular redox environment alters antigen presentation. AB - Cysteine-containing peptides represent an important class of T cell epitopes, yet their prevalence remains underestimated. We have established and interrogated a database of around 70,000 naturally processed MHC-bound peptides and demonstrate that cysteine-containing peptides are presented on the surface of cells in an MHC allomorph-dependent manner and comprise on average 5-10% of the immunopeptidome. A significant proportion of these peptides are oxidatively modified, most commonly through covalent linkage with the antioxidant glutathione. Unlike some of the previously reported cysteine-based modifications, this represents a true physiological alteration of cysteine residues. Furthermore, our results suggest that alterations in the cellular redox state induced by viral infection are communicated to the immune system through the presentation of S-glutathionylated viral peptides, resulting in altered T cell recognition. Our data provide a structural basis for how the glutathione modification alters recognition by virus specific T cells. Collectively, these results suggest that oxidative stress represents a mechanism for modulating the virus-specific T cell response. PMID- 25135639 TI - Interaction of platelet endothelial cell adhesion molecule (PECAM) with alpha2,6 sialylated glycan regulates its cell surface residency and anti-apoptotic role. AB - The luminal sides of vascular endothelial cells are heavily covered with a so called glycocalyx, but the precise role of the endothelial glycocalyx remains unclear. Our previous study showed that N-glycan alpha2,6-sialylation regulates the cell surface residency of an anti-apoptotic molecule, platelet endothelial cell adhesion molecule (PECAM), as well as the sensitivity of endothelial cells toward apoptotic stimuli. As PECAM itself was shown to be modified with biantennary N-glycans having alpha2,6-sialic acid, we expected that PECAM would possess lectin-like activity toward alpha2,6-sialic acid to ensure its homophilic interaction. To verify this, a series of oligosaccharides were initially added to observe their inhibitory effects on the homophilic PECAM interaction in vitro. We found that a longer alpha2,6-sialylated oligosaccharide exhibited strong inhibitory activity. Furthermore, we found that a cluster-type alpha2,6-sialyl N glycan probe specifically bound to PECAM-immobilized beads. Moreover, the addition of the alpha2,6-sialylated oligosaccharide to endothelial cells enhanced the internalization of PECAM as well as the sensitivity to apoptotic stimuli. Collectively, these findings suggest that PECAM is a sialic acid binding lectin and that this binding property supports endothelial cell survival. Notably, our findings that alpha2,6-sialylated glycans influenced the susceptibility to endothelial cell apoptosis shed light on the possibility of using a glycan-based method to modulate angiogenesis. PMID- 25135641 TI - Glycomic characterization of respiratory tract tissues of ferrets: implications for its use in influenza virus infection studies. AB - The initial recognition between influenza virus and the host cell is mediated by interactions between the viral surface protein hemagglutinin and sialic acid terminated glycoconjugates on the host cell surface. The sialic acid residues can be linked to the adjacent monosaccharide by alpha2-3- or alpha2-6-type glycosidic bonds. It is this linkage difference that primarily defines the species barrier of the influenza virus infection with alpha2-3 binding being associated with avian influenza viruses and alpha2-6 binding being associated with human strains. The ferret has been extensively used as an animal model to study the transmission of influenza. To better understand the validity of this model system, we undertook glycomic characterization of respiratory tissues of ferret, which allows a comparison of potential viral receptors to be made between humans and ferrets. To complement the structural analysis, lectin staining experiments were performed to characterize the regional distributions of glycans along the respiratory tract of ferrets. Finally, the binding between the glycans identified and the hemagglutinins of different strains of influenza viruses was assessed by glycan array experiments. Our data indicated that the respiratory tissues of ferret heterogeneously express both alpha2-3- and alpha2-6-linked sialic acids. However, the respiratory tissues of ferret also expressed the Sda epitope (NeuAcalpha2-3(GalNAcbeta1-4)Galbeta1-4GlcNAc) and sialylated N,N' diacetyllactosamine (NeuAcalpha2-6GalNAcbeta1-4GlcNAc), which have not been observed in the human respiratory tract surface epithelium. The presence of the Sda epitope reduces potential binding sites for avian viruses and thus may have implications for the usefulness of the ferret in the study of influenza virus infection. PMID- 25135640 TI - Structural maintenance of chromosome (SMC) proteins link microtubule stability to genome integrity. AB - Structural maintenance of chromosome (SMC) proteins are key organizers of chromosome architecture and are essential for genome integrity. They act by binding to chromatin and connecting distinct parts of chromosomes together. Interestingly, their potential role in providing connections between chromatin and the mitotic spindle has not been explored. Here, we show that yeast SMC proteins bind directly to microtubules and can provide a functional link between microtubules and DNA. We mapped the microtubule-binding region of Smc5 and generated a mutant with impaired microtubule binding activity. This mutant is viable in yeast but exhibited a cold-specific conditional lethality associated with mitotic arrest, aberrant spindle structures, and chromosome segregation defects. In an in vitro reconstitution assay, this Smc5 mutant also showed a compromised ability to protect microtubules from cold-induced depolymerization. Collectively, these findings demonstrate that SMC proteins can bind to and stabilize microtubules and that SMC-microtubule interactions are essential to establish a robust system to maintain genome integrity. PMID- 25135642 TI - Molecular characterization of arylsulfatase G: expression, processing, glycosylation, transport, and activity. AB - Arylsulfatase G (ARSG) is a recently identified lysosomal sulfatase that was shown to be responsible for the degradation of 3-O-sulfated N-sulfoglucosamine residues of heparan sulfate glycosaminoglycans. Deficiency of ARSG leads to a new type of mucopolysaccharidosis, as described in a mouse model. Here, we provide a detailed molecular characterization of the endogenous murine enzyme. ARSG is expressed and proteolytically processed in a tissue-specific manner. The 63-kDa single-chain precursor protein localizes to pre-lysosomal compartments and tightly associates with organelle membranes, most likely the endoplasmic reticulum. In contrast, proteolytically processed ARSG fragments of 34-, 18-, and 10-kDa were found in lysosomal fractions and lost their membrane association. The processing sites and a disulfide bridge between the 18- and 10-kDa chains could be roughly mapped. Proteases participating in the processing were identified as cathepsins B and L. Proteolytic processing is dispensable for hydrolytic sulfatase activity in vitro. Lysosomal transport of ARSG in the liver is independent of mannose 6-phosphate, sortilin, and Limp2. However, mutation of glycosylation site N-497 abrogates transport of ARSG to lysosomes in human fibrosarcoma cells, due to impaired mannose 6-phosphate modification. PMID- 25135643 TI - Biochemical characterization of the topoisomerase domain of Methanopyrus kandleri topoisomerase V. AB - Topoisomerases are ubiquitous enzymes that modify the topological state of DNA inside the cell and are essential for several cellular processes. Topoisomerase V is the sole member of the type IC topoisomerase subtype. The topoisomerase domain has a unique fold among topoisomerases, and the putative active site residues show a distinct arrangement. The present study was aimed at identifying the roles of the putative active site residues in the DNA cleavage/religation process. Residues Arg-131, Arg-144, His-200, Glu-215, Lys-218, and Tyr-226 were mutated individually to a series of conservative and non-conservative amino acids, and the DNA relaxation activity at different pH values, times, and enzyme concentrations was compared with wild-type activity. The results suggest that Arg 144 is essential for protein stability because any substitution at this position was deleterious and that Arg-131 and His-200 are involved in transition state stabilization. Glu-215 reduces the DNA binding ability of topoisomerase V, especially in shorter fragments with fewer helix-hairpin-helix DNA binding motifs. Finally, Lys-218 appears to play a direct role in catalysis but not in charge stabilization of the protein-DNA intermediate complex. The results suggest that although catalytically important residues are oriented in different fashions in the active sites of type IB and type IC topoisomerases, similar amino acids play equivalent roles in both of these subtypes of enzymes, showing convergent evolution of the catalytic mechanism. PMID- 25135645 TI - Crystal chemistry and selected physical properties of inorganic fluorides and oxide-fluorides. PMID- 25135644 TI - Organizational interplay of Golgi N-glycosyltransferases involves organelle microenvironment-dependent transitions between enzyme homo- and heteromers. AB - Glycosylation of proteins and lipids takes place in the Golgi apparatus by the consecutive actions of functionally distinct glycosidases and glycosyltransferases. Current evidence indicates that they function as enzyme homomers and/or heteromers in the living cell. Here we investigate their organizational interplay and show that glycosyltransferase homomers are assembled in the endoplasmic reticulum. Upon transport to the Golgi, the majority of homomers are disassembled to allow the formation of enzyme heteromers between sequentially acting medial-Golgi enzymes GnT-I and GnT-II or trans-Golgi enzymes GalT-I and ST6Gal-I. This transition is driven by the acidic Golgi environment, as it was markedly inhibited by raising Golgi luminal pH with chloroquine. Our FRAP (fluorescence recovery after photobleaching) measurements showed that the complexes remain mobile Golgi membrane constituents that can relocate to the endoplasmic reticulum or to the scattered Golgi mini-stacks upon brefeldin A or nocodazole treatment, respectively. During this relocation, heteromers undergo a reverse transition back to enzyme homomers. These data unveil an unprecedented organizational interplay between Golgi N-glycosyltransferases that involves dynamic and organelle microenvironment-driven transitions between enzyme homomers and heteromers during their trafficking within the early secretory compartments. PMID- 25135646 TI - Frequent cough in unsatisfactory controlled asthma--results from the population based West Sweden Asthma study. AB - BACKGROUND: Asthma is a complex disease presenting with variable symptoms which are sometimes hard to control. The purpose of the study was to describe the prevalence of asthma symptoms, use of asthma medications and allergic sensitization in subjects with asthma. We also related those indices to the level of asthma control, lung function and in particular, cough. METHODS: An extensive questionnaire was sent to randomly selected adults from the West Sweden region. Clinical examinations and interview were performed in a subset. Of the participants, 744 were defined as having an ongoing asthma - reported ever having asthma or physician diagnosed asthma and one of the following - use of asthma medications, recurrent wheeze or attacks of shortness of breath with or without wheeze in the last 12 months. A respiratory disease-free control group of 847 subjects was also described. RESULTS: According to GINA guidelines, 40.6% of the asthmatics had partly controlled and 17.8% had uncontrolled asthma. Asthmatic subjects reported significantly more symptoms in the last 12 months than the control group - wheezing (79.4 vs 9.2%), shortness of breath (36.1 vs 2.5%), wheezing with shortness of breath (58.7 vs 1.3%). Important complaints were morning cough (42.5 vs 15.5%), cough with sputum production (36.1 vs 6.8%) and longstanding cough (32.5 vs 11.1%), which bothered two thirds of the uncontrolled and one third of partly controlled subjects. Asthma medications were used by 87.5% of the asthmatics, although around 30% of them who had insufficiently controlled disease used only short-acting beta-agonists. Asthmatics also had lower lung function, reacted to lower doses of methacholine that the controls and 13.6% of them had a FEV1/FVC ratio below 0.7. Allergic rhinitis was reported by 73.8% of the asthmatics and they were more frequently sensitized to several common allergens. CONCLUSIONS: Approximately 60% of asthmatics from this population-based study had insufficiently controlled asthma and persistent complaints, despite a high use of asthma medications. These self-reported symptoms were supported by clinical examination data. Increased cough frequency is an indicator of a more severe and difficult to control disease and should be considered when asthma is characterized. PMID- 25135647 TI - Lipopolysaccharide induced LOX-1 expression via TLR4/MyD88/ROS activated p38MAPK NF-kappaB pathway. AB - Lectin-like receptor for oxidized low density lipoprotein (LOX-1) plays a key role in endothelial ox-LDL endocytosis, endothelial dysfunction and atherogenesis. In the present study, the effect of lipopolysaccharide (LPS) on LOX-1 expression and the underlying molecular pathways were investigated. Human umbilical vein endothelial cells (HUVECs) were treated with LPS and the protein expressions of LOX-1, TLR4, TLR2, MyD88, Nox4, Nox2, PI3K, p38MAPK, JNK, ERK, Nrf1, Nrf2 and p65 were examined by Western blotting. The intracellular reactive oxygen species (ROS) production was examined by flow cytometry with fluorescence probe DCFH2-DA. The role of TLR4, MyD88 and Nox4 were determined with specific siRNA. The endothelial ox-LDL uptake and the endothelial-monocyte adhesion were evaluated with DiI-ox-LDL and Hoechst 33342 respectively. The effect of LPS on LOX-1 expression in aorta tissue was also studied with male C57/BL6 mice by intraperitoneal injection of LPS. The results showed that LPS induced LOX-1 protein expression in a time- and concentration-dependent manner. The mRNA expression of LOX-1 was also upregulated. The protein expression of LOX-1 and phosphorylated p38MAPK, p65 was significantly enhanced by LPS both in vitro and in vivo. LPS induced LOX-1 expression was blocked by siRNA for TLR4, MyD88, and Nox4 and inhibitors for p38MAPK, NF-kappaB, cyclooxygenase-2, and NADPH oxidase. Both LPS induced ox-LDL uptake and endothelial-monocyte adhesion were significantly inhibited by anti-LOX-1 antibody. LPS dramatically induced LOX-1 protein expression in aorta tissues. In conclusion, our data suggested that LPS induces LOX-1 expression via TLR4/MyD88/ROS activated p38MAPK/NF-kappaB pathway in endothelial cells, which provides new regulatory mechanisms for LOX-1 expression. PMID- 25135648 TI - Activation of Nrf2 by dimethyl fumarate improves vascular calcification. AB - Dimethyl fumarate (DMF) has several pharmacological benefits including immunomodulation and prevention of fibrosis, which are dependent on the NF-E2 related factor 2 (Nrf2) antioxidant pathways. Therefore, we hypothesized that DMF could attenuate vascular calcification via Nrf2 activation. Vascular calcification induced by hyperphosphataemia was significantly inhibited by DMF in vascular smooth muscle cells (VSMCs) in a dose-dependent manner. DMF-mediated Nrf2 upregulation was accompanied by the reduced expressions of genes related with osteoblast-like phenotype based on promoter activity, mRNA and protein expression, and von Kossa staining. Likewise, Nrf2 overexpression significantly decreased the formation of calcium deposit similar to the level of osteogenic staining in VSMCs, and DMF with Nrf2 knockdown failed to attenuate hyperphosphatemia induced vascular calcification. Furthermore, DMF significantly attenuated the calcification of ex vivo ring culture from both rat common carotid artery and mouse thoracic aorta as well as in vivo mouse model of Vitamin D3 induced calcification consistent with the increased Nrf2 protein levels in early stage of calcification by DMF. In conclusion, our data support that DMF stimulates Nrf2 activity to attenuate hyperphosphatamia in vitro or Vitamin D3 induced in vivo vascular calcification, which would be a beneficial effect on vascular diseases induced by oxidative stress such as vascular calcification. PMID- 25135649 TI - Treatment of preeclampsia: current approach and future perspectives. AB - Hypertension is the most common medical disorder encountered during pregnancy, occurring in about 6-8 % of pregnancies. Preeclampsia is a pregnancy-specific disorder that occurs after 20 weeks' gestation, characterized by hypertension and proteinuria. Preeclampsia can also occur superimposed upon chronic hypertension. Eclampsia is the convulsive form of preeclampsia, and affects 0.1 % of all pregnancies. In low-income and middle-income countries, preeclampsia and eclampsia are associated with 10-15 % of direct maternal deaths. Women who develop preeclampsia in pregnancy are at greater risk of cardiovascular and cerebrovascular events even years after their pregnancies. There is significant progress in the elucidation of the underlying mechanisms and pathophysiology of preeclampsia, although its therapeutics remains challenging; delivery of the fetus is still the definitive treatment. Different international societies have produced recommendations and guidelines for clinicians treating preeclampsia, with an overall goal of improving maternal and fetal outcomes. In this review, we focus on the level of blood pressure at which to commence treatment and the current clinical management strategies available to treat and possibly prevent preeclampsia. We also briefly outline some newer perspectives on management of the disorder. PMID- 25135650 TI - Severe and refractory solar urticaria treated with intravenous immunoglobulins: a phase II multicenter study. AB - BACKGROUND: Retrospective data have suggested the effectiveness of intravenous immunoglobulins (IVIG) for solar urticaria (SU). OBJECTIVE: We sought to prospectively assess the efficacy of IVIG for SU. METHODS: We conducted a multicentric phase II study to test the efficacy of a single course of IVIG (2 g/kg) in patients with severe and refractory SU. The primary outcome was remission of SU on phototesting at 12 weeks after IVIG treatment. Secondary objectives included clinical remission, improved quality of life, and 50% improvement in disease intensity as measured on a visual analog scale. RESULTS: Of the 9 patients who received IVIG injection, 2 showed remission of SU on phototesting, corresponding to a response rate of 22.2% (95% confidence interval 2.8%-60.0%). In all, 6 patients (67%) showed at least 1 response criterion after 4 weeks and 5 (56%) after 12 weeks. Response was maintained after 24 weeks for 2 patients and after 48 weeks for 1 patient. About half of the patients (56%) had moderate to severe headache. LIMITATIONS: Lack of control arm and small number of patients are limitations. CONCLUSION: A single course of IVIG appears insufficient to obtain prolonged significant control of SU; future evaluation of different schedules of IVIG administration is warranted. PMID- 25135651 TI - Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels. AB - BACKGROUND: Port-wine stain (PWS) is a congenital, progressive vascular malformation but the pathogenesis remains incompletely understood. OBJECTIVE: We sought to investigate the activation status of various kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, AKT, phosphatidylinositol 3-kinase, P70 ribosomal S6 kinase, and phosphoinositide phospholipase C gamma subunit, in PWS biopsy tissues. METHODS: Immunohistochemistry was performed on 19 skin biopsy samples from 11 patients with PWS. RESULTS: c-Jun N-terminal kinase, extracellular signal-regulated kinase, and P70 ribosomal S6 kinase in pediatric and adult PWS blood vessels were consecutively activated. Activation of AKT and phosphatidylinositol 3-kinase was found in many adult hypertrophic PWS blood vessels but not in infants. Phosphoinositide phospholipase C gamma subunit showed strong activation in nodular PWS blood vessels. LIMITATION: Infantile PWS sample size was small. CONCLUSION: Our data suggest a subsequent activation profile of various kinases during different stages of PWS: (1) c-Jun N-terminal and extracellular signal regulated kinases are firstly and consecutively activated in all PWS tissues, which may contribute to both the pathogenesis and progressive development of PWS; (2) AKT and phosphatidylinositol 3-kinase are subsequently activated, and are involved in the hypertrophic development of PWS blood vessels; and (3) phosphoinositide phospholipase C gamma subunit is activated in the most advanced stage of PWS and may participate in nodular formation. PMID- 25135653 TI - What efficacy measures are clinically relevant and should be used in Cochrane Reviews of acute migraine trials? A viewpoint. AB - BACKGROUND: Cochrane Reviews are methodologically of high quality but the clinical relevance of analysed efficacy measures (EMs) should also be assessed. METHODS: The clinical relevance of EMs used in one systematic Cochrane review of oral zolmitriptan for migraine headache was evaluated. RESULTS: The following EMs were used: pain free at two hours (30%), headache relief at two hours (60%), sustained pain free for 24 hours (19%) and sustained headache relief for 24 hours (39%). These EMs were also used in four other Cochrane reviews of acute migraine treatment. Of these EMs sustained headache relief for 24 h is not judged clinically relevant. CONCLUSION: Pain free and sustained pain free are clinically relevant, but the responses are rather low, demonstrating that there is a need for improvement of acute drug treatment in migraine. PMID- 25135654 TI - Herpes zoster ophthalmicus following onabotulinumtoxinA administration for chronic migraine: a case report and literature review. AB - BACKGROUND: There is a growing body of literature documenting local herpes zoster outbreak following procedures. The mechanism underlying these outbreaks remains elusive. We present a case of zoster following onabotulinumtoxinA (BTX) for migraine and a literature review. METHODS: Chart and literature review. CASE: A 72-year-old woman with chronic migraine received BTX injections for 3 years without incident. She had a history of thoracic zoster with subsequent post herpetic neuralgia. In August 2013, 48 hours after receiving BTX injections, she developed a painful rash in the right V1 distribution consistent with herpes zoster ophthalmicus. One week later the rash had resolved without treatment. LITERATURE REVIEW: We identified 65 (including 2 from Juel-Jenson) cases of zoster reactivation following minor procedures. These cases tend to be in young patients without specific risk factors. Outbreaks characteristically occur at the level of exposure to local trauma. DISCUSSION: Our review suggests that local trauma, regardless of the nature of stimuli, may be sufficient for zoster reactivation. We hypothesize that the stressors in these reported cases exert a local epigenetic influence on viral transcription, allowing for viral reactivation. CONCLUSION: Zoster is a potential complication of BTX administration for chronic migraine in adults. Physician awareness can reduce the significant morbidity associated with this disease. PMID- 25135652 TI - A longitudinal study of urea cycle disorders. AB - The Urea Cycle Disorders Consortium (UCDC) is a member of the NIH funded Rare Diseases Clinical Research Network and is performing a longitudinal study of 8 urea cycle disorders (UCDs) with initial enrollment beginning in 2006. The consortium consists of 14 sites in the U.S., Canada and Europe. This report summarizes data mining studies of 614 patients with UCDs enrolled in the UCDC's longitudinal study protocol. The most common disorder is ornithine transcarbamylase deficiency, accounting for more than half of the participants. We calculated the overall prevalence of urea cycle disorders to be 1/35,000, with 2/3rds presenting initial symptoms after the newborn period. We found the mortality rate to be 24% in neonatal onset cases and 11% in late onset cases. The most common precipitant of clinical hyperammonemic episodes in the post-neonatal period was intercurrent infections. Elevations in both blood ammonia and glutamine appeared to be biomarkers for neurocognitive outcome. In terms of chronic treatment, low protein diet appeared to result in normal weight but decreased linear growth while N-scavenger therapy with phenylbutyrate resulted in low levels of branched chain amino acids. Finally, we found an unexpectedly high risk for hepatic dysfunction in patients with ornithine transcarbamylase deficiency. This natural history study illustrates how a collaborative study of a rare genetic disorder can result in an improved understanding of morbidity and disease outcome. PMID- 25135656 TI - Hospital end-of-life treatment intensity among cancer and non-cancer cohorts. AB - CONTEXT: Hospitals vary substantially in their end-of-life (EOL) treatment intensity. It is unknown if patterns of EOL treatment intensity are consistent across conditions. OBJECTIVES: To explore the relationship between hospitals' cancer- and non-cancer-specific EOL treatment intensity. METHODS: We conducted a retrospective cohort analysis of Pennsylvania acute care hospital admissions for either cancer or congestive heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD) between 2001 and 2007, linked to vital statistics through 2008. We calculated Bayes's shrunken case-mix standardized (observed-to expected) ratios of intensive care and life-sustaining treatment use among two EOL cohorts: those prospectively identified at high probability of dying on admission and those retrospectively identified as terminal admissions (decedents). We then summed these to create a hospital-specific prospective and retrospective overall EOL treatment intensity index for cancer vs. CHF/COPD. RESULTS: The sample included 207,523 admissions with 15% or greater predicted probability of dying on admission among 172,041 unique adults and 120,372 terminal admissions at 166 hospitals; these two cohorts overlapped by 52,986 admissions. There was substantial variation between hospitals in their standardized EOL treatment intensity ratios among cancer and CHF/COPD admissions. Within hospitals, cancer- and CHF/COPD-specific standardized EOL treatment intensity ratios were highly correlated for intensive care unit (ICU) admission (prospective rho = 0.81; retrospective rho = 0.78), ICU lengths of stay (rho = 0.76; 0.64), mechanical ventilation (rho = 0.73; 0.73), and hemodialysis (rho = 0.60; 0.71) and less highly correlated for tracheostomy (rho = 0.43; 0.53) and gastrostomy (rho = 0.29; 0.30). Hospitals' overall EOL intensity index for cancer and CHF admissions were correlated (prospective rho = 0.75; retrospective rho = 0.75) and had equal group means (P-value = 0.631; 0.699). CONCLUSION: Despite substantial difference between hospitals in EOL treatment intensity, within hospital homogeneity in EOL treatment intensity for cancer- and non-cancer populations suggests the existence of condition-insensitive institutional norms of EOL treatment. PMID- 25135655 TI - Differential expression of microRNAs in decidua-derived mesenchymal stem cells from patients with pre-eclampsia. AB - BACKGROUND: Mesenchymal stem cells (MSCs) at maternal-fetal interface are considered to play an important role in the pathogenesis of pre-eclampsia (PE). microRNAs (miRNAs) also have an important influence on differentiation, maturation, and functions of MSCs. Our aim in this study was to determine the differential expression of miRNAs in decidua-derived MSCs (dMSCs) from severe PE and normal pregnancies. RESULTS: miRNA expression profiles in dMSCs from five patients with severe PE and five healthy pregnant women were screened using microarray. Then, bioinformatic analysis of the microarray results was performed. Out of 179 differentially expressed miRNAs, 49 miRNAs had significant (p < 0.05) differential expression of >= 2.0-fold changes, including 21 up-regulated and 28 down-regulated. miRNA-Gene-network and miRNA-Gene ontology (GO) -network analyses were performed. Overall, 21 up-regulated and 15 down-regulated miRNAs showed high degrees in these analyses. Moreover, the significantly enriched signaling pathways and GOs were identified. The analyses revealed that pathways associated with cell proliferation, angiogenesis, and immune functions were highly regulated by the differentially expressed miRNAs, including Wnt signaling pathway, mitogen activated protein kinase signaling pathway, transforming growth factor beta signaling pathway, T-cell receptor signaling pathway, and B cell receptor signaling pathway. Four miRNA predicted target genes, vascular endothelial growth factor A (VEGFA), indoleamine 2,3-dioxygenase, suppression of cytokine signaling 3, and serine/threonine protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform (PPP2R2A) were all decreased in dMSCs from patients with PE. Furthermore, the physiological roles of miR-16 and miR-136 in the down-regulation of VEGFA and PPP2R2A, respectively, were confirmed through reporter assays. CONCLUSIONS: These findings suggest that miRNAs in dMSCs may be important regulatory molecules in the development of PE. PMID- 25135657 TI - Capture, transfer, and feedback of patient-centered outcomes data in palliative care populations: does it make a difference? A systematic review. AB - CONTEXT: Patient-centered outcome measures (PCOMs) are an important way of promoting patient-professional communication. However, evidence regarding their implementation in palliative care is limited, as is evidence of the impact on care quality and outcomes. OBJECTIVES: The aim was to systematically review evidence on capture and feedback of PCOMs in palliative care populations and determine the effects on processes and outcomes of care. METHODS: We searched Medline, Embase, CINAHL, BNI, PsycINFO, and gray literature from 1985 to October 2013 for peer-reviewed articles focusing on collection, transfer, and feedback of PCOMs in palliative care populations. Two researchers independently reviewed all included articles. Review articles, feasibility studies, and those not measuring PCOMs in clinical practice were excluded. We quality assessed articles using modified Edwards criteria and undertook narrative synthesis. RESULTS: One hundred eighty-four articles used 122 different PCOMs in 70,466 patients. Of these, 16 articles corresponding to 13 studies met the full inclusion criteria. Most evidence was from outpatient oncology. There was strong evidence for an impact of PCOMs feedback on processes of care including better symptom recognition, more discussion of quality of life, and increased referrals based on PCOMs reporting. There was evidence of improved emotional and psychological patient outcomes but no effect on overall quality of life or symptom burden. CONCLUSION: In palliative care populations, PCOMs feedback improves awareness of unmet need and allows professionals to act to address patients' needs. It consequently benefits patients' emotional and psychological quality of life. However, more high-quality evidence is needed in noncancer populations and across a wider range of settings. PMID- 25135658 TI - Fatigue is associated with serum interleukin-6 levels and symptoms of depression in patients on chronic hemodialysis. AB - CONTEXT: Little is known about activated immune-inflammatory pathways and interleukin-6 (IL-6) in the development of fatigue and/or depression in patients with end-stage renal disease on chronic hemodialysis (HD). OBJECTIVES: To evaluate the possible correlation between fatigue and serum levels of IL-6 in patients on chronic HD. METHODS: One hundred HD patients were assessed for the presence of fatigue using the SF-36 Vitality subscale and were administered the Beck Depression Inventory (BDI), the Hamilton Anxiety Rating Scale (HARS), the Mini-Mental State Examination (MMSE), the activities of daily living (ADL), and the instrumental activities of daily living (IADL). We also calculated the time of recovery after hemodialysis (TIRD) and the number/severity of comorbidities using the Charlson Comorbidity Index (CCI). Laboratory parameters were measured as well as serum IL-6. RESULTS: Forty-three patients constituted the fatigued group and 57 the nonfatigued group. Age, CCI, BDI, HARS, and TIRD were significantly higher in fatigued patients than in the nonfatigued patients. Conversely, the scores of ADL, IADL, and MMSE were significantly lower in fatigued than in nonfatigued patients. Serum IL-6 levels (pg/mL) were higher in the fatigued group (5.1 +/- 3.4) than in the nonfatigued group (1.6 +/- 1.5; P < 0.001); serum albumin and creatinine levels were significantly lower. Twenty-six patients (26%) had no symptoms of depression (BDI score <10), and 74 patients (74%) had symptoms of depression (BDI score >9). Patients with a BDI score >9 were older; had a higher CCI; a lower MMSE; a higher TIRD; lower serum albumin, creatinine, and urea levels; and higher serum IL-6 levels. The correlation analyses showed that the score of the SF-36 Vitality subscale was associated with age, dialytic age, TIRD, ADL, IADL, CCI, BDI, HARS, MMSE, serum urea, creatinine, albumin, and IL-6 levels. On multivariate general linear model analyses, with fatigue as the dependent variable and gender as a second factor, BDI and serum IL 6 levels were independently associated with the score of the SF-36 Vitality subscale. A canonical correlation analysis was performed including in the model fatigue, BDI, and biomarkers; the correlation was 0.679 (R(2) = 0.462). Fatigue, BDI, and IL-6 among biomarkers showed the strongest association with the underlying construct (standardized canonical coefficients = -0.989, 0.015, and 0.852, respectively), thus explaining a correlation of IL-6 with both depression and fatigue. CONCLUSION: Fatigue was significantly associated with symptoms of depression and serum IL-6 levels in patients receiving chronic HD. PMID- 25135660 TI - Effects of cargo molecules on membrane perturbation caused by transportan10 based cell-penetrating peptides. AB - Cell-penetrating peptides with the ability to escape endosomes and reach the target are of great value as delivery vectors for different bioactive cargoes and future treatment of human diseases. We have studied two such peptides, NickFect1 and NickFect51, both originated from stearylated transportan10 (PF3). To obtain more insight into the mechanism(s) of peptide delivery and the biophysical properties of an efficient vector system, we investigated the effect of different bioactive oligonucleotide cargoes on peptide-membrane perturbation and peptide structural induction. We studied the membrane interactions of the peptides with large unilamellar vesicles and compared their effects with parent peptides transportan10 and PF3. In addition, cellular uptake and peptide-mediated oligonucleotide delivery were analyzed. Calcein leakage experiments showed that similar to transportan10, NickFect51 caused a significant degree of membrane leakage, whereas NickFect1, similar to PF3, was less membrane perturbing. The results are in agreement with previously published results indicating that NickFect51 is a more efficient endosomal escaper. However, the presence of a large cargo like plasmid DNA inhibited NickFect's membrane perturbation and cellular uptake efficiency of the peptide was reduced. We conclude that the pathway for cellular uptake of peptide complexes is cargo dependent, whereas the endosomal escape efficacy depends on peptide hydrophobicity and chemical structure. For small interfering RNA delivery, NickFect51 appears to be optimal. The biophysical signature shows that the peptide alone causes membrane perturbation, but the cargo complex does not. These two biophysical characteristics of the peptide and its cargo complex may be the signature of an efficient delivery vector system. PMID- 25135659 TI - Revisiting the bilayer structures of fluid phase phosphatidylglycerol lipids: Accounting for exchangeable hydrogens. AB - We recently published two papers detailing the structures of fluid phase phosphatidylglycerol (PG) lipid bilayers (Kucerka et al., 2012 J. Phys. Chem. B 116: 232-239; Pan et al., 2012 Biochim. Biophys. Acta Biomembr. 1818: 2135-2148), which were determined using the scattering density profile model. This hybrid experimental/computational technique utilizes molecular dynamics simulations to parse a lipid bilayer into components whose volume probabilities follow simple analytical functional forms. Given the appropriate scattering densities, these volume probabilities are then translated into neutron scattering length density (NSLD) and electron density (ED) profiles, which are used to jointly refine experimentally obtained small angle neutron and X-ray scattering data. However, accurate NSLD and ED profiles can only be obtained if the bilayer's chemical composition is known. Specifically, in the case of neutron scattering, the lipid's exchangeable hydrogens with aqueous D2O must be accounted for, as they can have a measureable effect on the resultant lipid bilayer structures. This was not done in our above-mentioned papers. Here we report on the molecular structures of PG lipid bilayers by appropriately taking into account the exchangeable hydrogens. Analysis indicates that the temperature-averaged PG lipid areas decrease by 1.5 to 3.8A(2), depending on the lipid's acyl chain length and unsaturation, compared to PG areas when hydrogen exchange was not taken into account. PMID- 25135661 TI - Biochemical characterization and structure-function relationship of two plant NCS2 proteins, the nucleobase transporters NAT3 and NAT12 from Arabidopsis thaliana. AB - Nucleobase ascorbate transporters (NATs), also known as Nucleobase:Cation Symporter 2 (NCS2) proteins, belong to an evolutionary widespread family of transport proteins with members in nearly all domains of life. We present the biochemical characterization of two NAT proteins, NAT3 and NAT12 from Arabidopsis thaliana after their heterologous expression in Escherichia coli UraA knockout mutants. Both proteins were shown to transport adenine, guanine and uracil with high affinities. The apparent KM values were determined with 10.12MUM, 4.85MUM and 19.95MUM, respectively for NAT3 and 1.74MUM, 2.44MUM and 29.83MUM, respectively for NAT12. Competition studies with the three substrates suggest hypoxanthine as a further substrate of both transporters. Furthermore, the transport of nucleobases was markedly inhibited by low concentrations of a proton uncoupler indicating that NAT3 and NAT12 act as proton-nucleobase symporters. Transient expression studies of NAT-GFP fusion constructs revealed a localization of both proteins in the plasma membrane. Based on the structural information of the uracil permease UraA from E. coli, a three-dimensional experimentally validated homology model of NAT12 was created. The NAT12 structural model is composed of 14 TM segments and divided into two inverted repeats of TM1-7 and TM8 14. Docking studies and mutational analyses identified residues involved in NAT12 nucleobase binding including Ser-247, Phe-248, Asp-461, Thr-507 and Thr-508. This is the first study to provide insight into the structure-function of plant NAT proteins, which reveals differences from the other members of the NCS2 protein family. PMID- 25135662 TI - Quantification of leakage from large unilamellar lipid vesicles by fluorescence correlation spectroscopy. AB - Fluorescence correlation spectroscopy (FCS) is a powerful experimental technique that in recent years has found numerous applications for studying biological phenomena. In this article, we scrutinize one of these applications, namely, FCS as a technique for studying leakage of fluorescent molecules from large unilamellar lipid vesicles. Specifically, we derive the mathematical framework required for using FCS to quantify leakage of fluorescent molecules from large unilamellar lipid vesicles, and we describe the appropriate methodology for successful completion of FCS experiments. By use of this methodology, we show that FCS can be used to accurately quantify leakage of fluorescent molecules from large unilamellar lipid vesicles, including leakage of fluorescent molecules of different sizes. To demonstrate the applicability of FCS, we have investigated the antimicrobial peptide mastoparan X. We show that mastoparan X forms transient transmembrane pores in POPC/POPG (3:1) vesicles, resulting in size-dependent leakage of molecules from the vesicles. We conclude the paper by discussing some of the advantages and limitations of FCS as compared to other existing methods to measure leakage from large unilamellar lipid vesicles. PMID- 25135663 TI - The periplasmic domain of Escherichia coli outer membrane protein A can undergo a localized temperature dependent structural transition. AB - Gram-negative bacteria such as Escherichia coli are surrounded by two membranes with a thin peptidoglycan (PG)-layer located in between them in the periplasmic space. The outer membrane protein A (OmpA) is a 325-residue protein and it is the major protein component of the outer membrane of E. coli. Previous structure determinations have focused on the N-terminal fragment (residues 1-171) of OmpA, which forms an eight stranded transmembrane beta-barrel in the outer membrane. Consequently it was suggested that OmpA is composed of two independently folded domains in which the N-terminal beta-barrel traverses the outer membrane and the C-terminal domain (residues 180-325) adopts a folded structure in the periplasmic space. However, some reports have proposed that full-length OmpA can instead refold in a temperature dependent manner into a single domain forming a larger transmembrane pore. Here, we have determined the NMR solution structure of the C terminal periplasmic domain of E. coli OmpA (OmpA(180-325)). Our structure reveals that the C-terminal domain folds independently into a stable globular structure that is homologous to the previously reported PG-associated domain of Neisseria meningitides RmpM. Our results lend credence to the two domain structure model and a PG-binding function for OmpA, and we could indeed localize the PG-binding site on the protein through NMR chemical shift perturbation experiments. On the other hand, we found no evidence for binding of OmpA(180-325) with the TonB protein. In addition, we have also expressed and purified full length OmpA (OmpA(1-325)) to study the structure of the full-length protein in micelles and nanodiscs by NMR spectroscopy. In both membrane mimetic environments, the recombinant OmpA maintains its two domain structure that is connected through a flexible linker. A series of temperature-dependent HSQC experiments and relaxation dispersion NMR experiments detected structural destabilization in the bulge region of the periplasmic domain of OmpA above physiological temperatures, which may induce dimerization and play a role in triggering the previously reported larger pore formation. PMID- 25135665 TI - Exciting: a full-potential all-electron package implementing density-functional theory and many-body perturbation theory. AB - Linearized augmented planewave methods are known as the most precise numerical schemes for solving the Kohn-Sham equations of density-functional theory (DFT). In this review, we describe how this method is realized in the all-electron full potential computer package, exciting. We emphasize the variety of different related basis sets, subsumed as (linearized) augmented planewave plus local orbital methods, discussing their pros and cons and we show that extremely high accuracy (microhartrees) can be achieved if the basis is chosen carefully. As the name of the code suggests, exciting is not restricted to ground-state calculations, but has a major focus on excited-state properties. It includes time dependent DFT in the linear-response regime with various static and dynamical exchange-correlation kernels. These are preferably used to compute optical and electron-loss spectra for metals, molecules and semiconductors with weak electron hole interactions. exciting makes use of many-body perturbation theory for charged and neutral excitations. To obtain the quasi-particle band structure, the GW approach is implemented in the single-shot approximation, known as G(0)W(0). Optical absorption spectra for valence and core excitations are handled by the solution of the Bethe-Salpeter equation, which allows for the description of strongly bound excitons. Besides these aspects concerning methodology, we demonstrate the broad range of possible applications by prototypical examples, comprising elastic properties, phonons, thermal-expansion coefficients, dielectric tensors and loss functions, magneto-optical Kerr effect, core-level spectra and more. PMID- 25135664 TI - Conformational heterogeneity of alpha-synuclein in membrane. AB - alpha-Synuclein (alphaS) is a natively disordered protein in solution, thought to be involved in the fusion of neurotransmitter vesicles to cellular membranes during neurotransmission. Monomeric alphaS has been previously characterized in two distinct membrane-associated conformations: a broken-helix structure, and an extended helix. By employing atomistic molecular dynamics and a novel membrane representation with significantly enhanced lipid mobility (HMMM), we investigate the process of spontaneous membrane binding of alphaS and the conformational dynamics of monomeric alphaS in its membrane-bound form. By repeatedly placing helical alphaS monomers in solution above a planar lipid bilayer and observing their spontaneous association and its spontaneous insertion into the membrane during twenty independent unbiased simulations, we are able to characterize alphaS in its membrane-bound state, suggesting that alphaS has a highly variable membrane insertion depth at equilibrium. Our simulations also capture two distinct states of alphaS, the starting broken-helix conformation seen in the micelle bound NMR structures, and a semi-extended helix. Analysis of lipid distributions near alphaS monomers indicates that the transition to a semi extended helix is facilitated by concentration of phosphatidyl-serine headgroups along the inner edge of the protein. Such a lipid-mediated transition between helix-turn-helix and extended conformations of alphaS may also occur in vivo, and may be important for the physiological function of alphaS. PMID- 25135666 TI - The effect of changing micro-scale physical environmental factors on an environment's invitingness for transportation cycling in adults: an exploratory study using manipulated photographs. AB - Previous studies have shown convincing evidence for positive relationships between transportation cycling in adults and macro-scale physical environmental factors. In contrast, relationships are less consistent for more changeable, micro-scale environmental factors. The majority of existing studies used observational study designs, which cannot determine causality. The present mixed methods study used manipulated photographs to determine causal relationships between micro-scale environmental factors and the environment's invitingness for transportation cycling. Further, interactions among environmental factors and moderating effects of gender, age and educational level were investigated. For this study, panoramic photograph of a street was manipulated on eight environmental factors: traffic, speed bump, general upkeep, evenness of the cycle path, vegetation, separation of motorized traffic, separation with sidewalk and cycle path width. Sixty-six middle-aged adults participated in the study and sorted the manipulated panoramic photographs from least to most inviting to cycle for transportation. Participants also provided qualitative data on how they sorted the streets. Multilevel cross-classified modelling was used to analyse the relationships between the environmental manipulations and the invitingness scores. The qualitative data were deductively categorized according to the environmental factors. All environmental factors, except for separation with sidewalk, proved to have a significant main effect on the invitingness-score for transportation cycling. Cycle path evenness appeared to have the strongest effect on the invitingness. This effect was even stronger in an environment with good compared to poorly overall upkeep. Another significant interaction effect showed that the invitingness decreased when both separations along the cycle path were present compared to only a separation with traffic. No moderating effects of the demographic factors on these relationships were found. Qualitative data confirmed the observed quantitative relationships and added depth and understanding. Current study shows that the use of manipulated photographs can be an effective way to examine environment-physical activity relationships. Our findings indicate that evenness of the cycle path may be a crucial environmental factor when aiming to increase a street's invitingness for transportation cycling among middle-aged adults. The findings of our exploratory study could be used to develop an environmental intervention to determine if our findings are applicable to real changes in cycling behavior. PMID- 25135668 TI - A self-report comorbidity questionnaire for haemodialysis patients. AB - BACKGROUND: Patients with end-stage renal disease (ESRD) have multiple comorbid conditions. Obtaining comorbidity data from medical records is cumbersome. A self report comorbidity questionnaire is a useful alternative. Our aim in this study was to examine the predictive value of a self-report comorbidity questionnaire in terms of survival in ESRD patients. METHODS: We studied a prospective cross sectional cohort of 282 haemodialysis (HD) patients in a single centre. Participants were administered the self-report questionnaire during an HD session. Information on their comorbidities was subsequently obtained from an examination of the patient's medical records. Levels of agreement between parameters derived from the questionnaire, and from the medical records, were examined. Participants were followed-up for 18 months to collect survival data. The influence on survival of comorbidity scores derived from the self-report data (the Composite Self-report Comorbidity Score [CSCS]) and from medical records data--the Charlson Comorbidity Index [CCI] were compared. RESULTS: The level of agreement between the self-report items and those obtained from medical records was almost perfect with respect the presence of diabetes (Kappa score kappa 0.97), substantial for heart disease and cancer (kappa 0.62 and kappa 0.72 respectively), moderate for liver disease (kappa 0.51), only fair for lung disease, arthritis, cerebrovascular disease, and depression (kappa 0.34, 0.35, 0.34 and 0.29 respectively). The CSCS was strongly predictive of survival in regression models (Nagelkerke R(2) value 0.202), with a predictive power similar to that of the CCI (Nagelkerke R(2) value 0.211). The influences of these two parameters were additive in the models--suggesting that these parameters make different contributions to the assessment of comorbidity. CONCLUSION: This self report comorbidity questionnaire is a viable tool to collect comorbidity data and may have a role in the prediction of short-term survival in patients with end stage renal disease on haemodialysis. Further work is required in this setting to refine the tool and define its role. PMID- 25135670 TI - Time-frequency analysis of the event-related potentials associated with the Stroop test. AB - Multiple executive processes are suggested to be engaged at Stroop test, and time frequency analysis is acknowledged to improve the informative utility of EEG in cognitive brain research. We aimed to investigate event-related oscillations associated with the Stroop test. EEG data was collected from 23 healthy volunteers while they performed a computer version of Stroop test. Both evoked (phase-locked) and total (phase-locked+non-phase-locked) oscillatory responses in the EEG were analyzed by wavelet transform. Data from the congruent (color-word matching) and incongruent stimuli (color-word non-matching) conditions are compared. In the incongruent condition, N450 wave was more negative and amplitude of the late slow wave was more positive. In the time-frequency plane, the fronto central total theta amplitude (300-700 ms) was larger in the incongruent condition. The evoked delta (250-600 ms) was larger in the congruent condition particularly over parieto-occipital regions. The larger frontal theta response in the incongruent condition was associated with the detection of interference and inhibition of the response to task-irrelevant features, while the larger evoked delta in the congruent condition was suggestive of the easier decision process owing to congruency between the physical attribute and the verbal meaning of the stimuli. Furthermore, in the incongruent condition, amplitude of the occipital total alpha in the very late phase (700-900 ms) was smaller. This prolonged desynchronization in the alpha band could be reflecting augmentation of attentional filters in visual modality for the next stimulus. These multiple findings on EEG time-frequency plane provide improved description of the overlapping processes in Stroop test. PMID- 25135671 TI - Local country food sources of methylmercury, selenium and omega-3 fatty acids in Nunavik, Northern Quebec. AB - Country foods are central to Inuit culture and replete in selenium (Se) and long chain omega-3 polyunsaturated fatty acids (n-3 PUFA). However, some marine country foods bioaccumulate high concentrations of methylmercury (MeHg). Se and n 3 are associated with several health benefits in Nunavik, Northern Quebec, but, recent studies show that prenatal MeHg exposure is associated with visual, cognitive and behavioral deficit later in childhood. The study objectives are to identify contemporary country food sources of MeHg, Se and long-chain n-3 PUFA in Nunavik, particularly among childbearing-age women, taking into account regional differences in consumption profiles. The contribution of different country foods to daily MeHg, Se, long-chain n-3 PUFA intake (MUg/kg body weight/day) was estimated using: (i) country food consumption and blood biomarkers data from the 2004 Nunavik Health Survey (387 women, 315 men), and (ii) data on MeHg, Se, long chain n-3 PUFA concentrations found in Nunavik wildlife species. In the region where most traditional beluga hunting takes place in Nunavik, the prevalence of at-risk blood Hg (>= 8 MUg/L) in childbearing-age women was 78.4%. While most country foods presently consumed contain low MeHg, beluga meat, not a staple of the Inuit diet, is the most important contributor to MeHg: up to two-thirds of MeHg intake in the beluga-hunting region (0.66 of MeHg intake) and to about one third in other regions. In contrast, seal liver and beluga mattaaq - beluga skin and blubber - only mildly contributed to MeHg (between 0.06 and 0.15 of MeHg intake), depending on the region. Beluga mattaaq also highly contributed to Se intake (0.30 of Se intake). Arctic char, beluga blubber and mattaaq, and seal blubber contributed to most long-chain n-3 PUFA intake. This study highlights the importance of considering interconnections between local ecosystems and dietary habits to develop recommendations and interventions promoting country foods' benefits, while minimizing the risk of MeHg from beluga meat, especially for childbearing-age women. PMID- 25135672 TI - The genome of a clinical Klebsiella variicola strain reveals virulence-associated traits and a pl9-like plasmid. AB - Klebsiella species frequently cause clinically relevant human infections worldwide. We report the draft genome sequence of a Brazilian clinical isolate (Bz19) of the recently recognized species Klebsiella variicola. The comparison of Bz19 genome content with the At-22 (environmental K. variicola) and several clinical Klebsiella pneumoniae shows that these species share a set of virulence associated determinants. Of note, this K. variicola strain harbours a plasmid like element that shares the same backbone present in a multidrug-resistant plasmid found in a clinical K. pneumoniae isolated in USA. PMID- 25135673 TI - Protein systems biology: method, regulation, and network. PMID- 25135669 TI - The development and application of a quantitative peptide microarray based approach to protein interaction domain specificity space. AB - Protein interaction domain (PID) linear peptide motif interactions direct diverse cellular processes in a specific and coordinated fashion. PID specificity, or the interaction selectivity derived from affinity preferences between possible PID peptide pairs is the basis of this ability. Here, we develop an integrated experimental and computational cellulose peptide conjugate microarray (CPCMA) based approach for the high throughput analysis of PID specificity that provides unprecedented quantitative resolution and reproducibility. As a test system, we quantify the specificity preferences of four Src Homology 2 domains and 124 physiological phosphopeptides to produce a novel quantitative interactome. The quantitative data set covers a broad affinity range, is highly precise, and agrees well with orthogonal biophysical validation, in vivo interactions, and peptide library trained algorithm predictions. In contrast to preceding approaches, the CPCMAs proved capable of confidently assigning interactions into affinity categories, resolving the subtle affinity contributions of residue correlations, and yielded predictive peptide motif affinity matrices. Unique CPCMA enabled modes of systems level analysis reveal a physiological interactome with expected node degree value decreasing as a function of affinity, resulting in minimal high affinity binding overlap between domains; uncover that Src Homology 2 domains bind ligands with a similar average affinity yet strikingly different levels of promiscuity and binding dynamic range; and parse with unprecedented quantitative resolution contextual factors directing specificity. The CPCMA platform promises broad application within the fields of PID specificity, synthetic biology, specificity focused drug design, and network biology. PMID- 25135674 TI - Identification of important positions within miRNAs by integrating sequential and structural features. AB - MicroRNA(miRNA) is a small, single stranded non-coding RNA which plays an important regulatory role in gene expression. Additionally, miRNAs perform crucial functions in a wide range of biological processes. These functions may be exploited for miRNA-mediated regulation of protein-protein interaction and thus protein function. Many computational methods have been developed to predict the miRNA targets and to explore the regulatory mechanism between miRNA and protein. However, the efforts to investigate important positions within miRNAs are not comprehensive. This paper presents a framework to identify important positions using collision entropy. The information of contained in the sequence and secondary structure of miRNAs is considered. Further, the single base collision entropy and the adjacent base related collision entropy are integrated to measure the importance of miRNA position. Two thresholds are employed to select those positions with more biological meaning. A dataset of Drosophila melanogaster is used in the experiments. The results demonstrate that our approach can find interesting and important positions within miRNAs and may lead to a better understanding of miRNA biogenesis and function. PMID- 25135675 TI - The effect of the different methods indicating 100/min to 120/min using the metronome in dispatcher-assisted resuscitation. PMID- 25135677 TI - The importance of lead aVR interpretation by emergency physicians. PMID- 25135676 TI - The impact of age and gender on resource utilization and profitability in ED patients seen and released. AB - OBJECTIVE: To determine how age and gender impact resource utilization and profitability in patients seen and released from an Emergency Department (ED). METHODS: Billing data for patients seen and released from an Emergency Department (ED) with >100,000 annual visits between 2003 and 2009 were collected. Resource utilization was measured by length of stay (placement in ED bed to leaving the bed) and direct clinical costs (e.g., ED nursing salary and benefits, pharmacy and supply costs, etc.) estimated using relative value unit cost accounting. The primary outcome of profitability was defined as contribution margin per hour. A patient's contribution margin by insurance type (excluding self-pay) was determined by subtracting direct clinical costs from facility contractual revenue. Results are expressed as medians and US dollars. RESULTS: In 523 882 outpatient ED encounters, as patients' aged, length of stay and direct clinical cost increased while the contribution margin and contribution margin by hour decreased. Women of childbearing age (15-44) had higher median length of stay (2.1 hours), direct clinical cost ($149), and contribution margin per hour ($103/hour) than men of same age (1.7, $131, $85/hour, respectively). Resource utilization and profitability by gender were similar in children and adults over 45. CONCLUSION: Resource utilization increased and profitability decreased with increasing age in patients seen and released from an ED. The care of women of childbearing age resulted in higher resource utilization and higher profitability than men of the same age. No differences in resource utilization or profitability by gender were observed in children and adults over 45. PMID- 25135678 TI - Reinforcement of anchorage during orthodontic brace treatment with implants or other surgical methods. AB - BACKGROUND: The term anchorage in orthodontic treatment refers to methods of controlling unwanted tooth movement. This is provided either by anchor sites within the mouth, such as the teeth and the palate, or from outside the mouth (headgear). Recently, new methods of providing anchorage have been developed using orthodontic implants which are surgically inserted into the bone in the mouth. This is termed surgical anchorage. This is an update of a Cochrane review first published in 2007. OBJECTIVES: To assess the effects of surgical anchorage techniques compared to conventional anchorage in the prevention of unwanted tooth movement in patients undergoing orthodontic treatment by evaluating the mesiodistal movement of upper first molar teeth. A secondary objective was to compare the effects of one type of surgical anchorage with another. SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 28 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE via OVID (1946 to 28 October 2013) and EMBASE via OVID (1980 to 28 October 2013). We handsearched key international orthodontic and dental journals, and searched the trial database ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled trials comparing surgical anchorage with conventional anchorage in orthodontic patients. Trials comparing two types of surgical anchorage were also included. DATA COLLECTION AND ANALYSIS: At least two review authors independently and in duplicate extracted data and carried out risk of bias assessments. We contacted study authors to clarify aspects of study design and conduct, and to obtain unreported data. MAIN RESULTS: Fourteen new studies were added in this update resulting in a total of 15 studies reporting data from 561 randomised patients. The studies were conducted in Europe, India, China, South Korea and the USA. The age range of patients was commonly restricted to adolescents or young adults, however the participants of two studies were from a much wider age range (12 to 54 years). The distribution of males and females was similar in eight of the studies, with a predominance of female patients in seven studies.Eight studies were assessed to be at high overall risk of bias; six studies at unclear risk of bias; one study at low risk of bias.Ten studies with 407 randomised and 390 analysed patients compared surgical anchorage with conventional anchorage for the primary outcome of mesiodistal movement of upper first molars. We carried out a random-effects model meta-analysis for the seven studies that fully reported this outcome. There was strong evidence of an effect of surgical anchorage on this outcome. Compared with conventional anchorage, surgical anchorage was more effective in the reinforcement of anchorage by 1.68 mm (95% confidence interval (CI) -2.27 mm to -1.09 mm; seven studies, 308 participants analysed) with moderate quality of evidence (one study at high overall risk of bias, five studies at unclear risk of bias, one study at low risk of bias). This result should be interpreted with some caution, however, as there was a substantial degree of heterogeneity for this comparison. There was no evidence of a difference in overall duration of treatment between surgical and conventional anchorage (-0.15 years; 95% CI -0.37 years to 0.07 years; three studies, 111 analysed patients) with low quality of evidence (one study at high overall risk of bias and two studies at unclear risk of bias). Information on patient-reported outcomes such as pain and acceptability was limited and inconclusive.When direct comparisons were made between two types of surgical anchorage, there was a lack of evidence to suggest that any one technique was better than another.No included studies reported adverse effects. AUTHORS' CONCLUSIONS: There is moderate quality evidence that reinforcement of anchorage is more effective with surgical anchorage than conventional anchorage, and that results from mini-screw implants are particularly promising. While surgical anchorage is not associated with the inherent risks and compliance issues related to extraoral headgear, none of the included studies reported on harms of surgical or conventional anchorage. PMID- 25135679 TI - Celebrating our success--one state at a time. PMID- 25135680 TI - Prevalence and outcomes of renal transplantation in children with intellectual disability. AB - To describe the prevalence and outcomes of renal transplantation in children with ID we performed a retrospective cohort analysis of all children receiving a first kidney-alone transplant in the UNOS dataset from 2008 to 2011. Recipients with definite, probable, and without ID were compared using chi-square tests. Kaplan Meier curves were constructed for patient and graft survival. Cox proportional hazard models were used to estimate the association between ID and graft failure and patient survival. Over the study period, 332 children with definite (117) or probable (215) ID underwent first renal transplant, accounting for 16% of all first pediatric renal transplants (n = 2076). Children with definite ID were not significantly different from children without ID with respect to sex, ethnicity, or prevalence of acute rejection. ID was associated with increased likelihood of deceased donor source. ID was not significantly associated with decreased graft or patient survival. In this first large-scale study, up to 16% of first pediatric renal transplants were performed in children with ID. Short-term graft and patient survival after transplant were equivalent between children with and without ID. Further research is needed to examine long-term outcomes of transplant in this population. PMID- 25135681 TI - Characterization of wheat germ agglutinin lectin-reactive glycosylated OmpA-like proteins derived from Porphyromonas gingivalis. AB - Glycosylation is one of the common posttranslational modifications in eukaryotes. Recently, glycosylated proteins have also been identified in prokaryotes. A few glycosylated proteins, including gingipains, have been identified in Porphyromonas gingivalis, a major pathogen associated with chronic periodontitis. However, no other glycosylated proteins have been found. The present study identified glycoproteins in P. gingivalis cell lysates by lectin blotting. Whole cell lysates reacted with concanavalin A (ConA), Lens culinaris agglutinin (LCA), Phaseolus vulgaris erythroagglutinin (PHA-E4), and wheat germ agglutinin (WGA), suggesting the presence of mannose-, N-acetylgalactosamine-, or N acetylglucosamine (GlcNAc)-modified proteins. Next, glycoproteins were isolated by ConA-, LCA-, PHA-E4-, or WGA-conjugated lectin affinity chromatography although specific proteins were enriched only by the WGA column. Mass spectrometry analysis showed that an OmpA-like, heterotrimeric complex formed by Pgm6 and Pgm7 (Pgm6/7) was the major glycoprotein isolated from P. gingivalis. Deglycosylation experiments and Western blotting with a specific antibody indicated that Pgm6/7 was modified with O-GlcNAc. When whole-cell lysates from P. gingivalis mutant strains with deletions of Pgm6 and Pgm7 were applied to a WGA column, homotrimeric Pgm7, but not Pgm6, was isolated. Heterotrimeric Pgm6/7 had the strongest affinity for fibronectin of all the extracellular proteins tested, whereas homotrimeric Pgm7 showed reduced binding activity. These findings suggest that the heterotrimeric structure is important for the biological activity of glycosylated WGA-binding OmpA-like proteins in P. gingivalis. PMID- 25135682 TI - Association and virulence gene expression vary among serotype III group B streptococcus isolates following exposure to decidual and lung epithelial cells. AB - Group B Streptococcus (GBS) causes severe disease in neonates, the elderly, and immunocompromised individuals. GBS species are highly diverse and can be classified by serotype and multilocus sequence typing. Sequence type 17 (ST-17) strains cause invasive neonatal disease more frequently than strains of other STs. Attachment and invasion of host cells are key steps in GBS pathogenesis. We investigated whether four serotype III strains representing ST-17 (two strains), ST-19, and ST-23 differ in their abilities to attach to and invade both decidual cells and lung epithelial cells. Virulence gene expression following host cell association and exposure to amnion cells was also tested. The ST-17 strains differed in their abilities to attach to and invade decidual cells, whereas there were no differences with lung epithelial cells. The ST-19 and ST-23 strains, however, attached to and invaded decidual cells less than both ST-17 strains. Although the ST-23 strain attached to lung epithelial cells better than ST-17 and -19 strains, none of the strains effectively invaded the lung epithelial cells. Notably, the association with host cells resulted in the differential expression of several virulence genes relative to basal expression levels. Similar expression patterns of some genes were observed regardless of cell type used. Collectively, these results show that GBS strains differ in their abilities to attach to distinct host cell types and express key virulence genes that are relevant to the disease process. Enhancing our understanding of pathogenic mechanisms could aid in the identification of novel therapeutic targets or vaccine candidates that could potentially decrease morbidity and mortality associated with neonatal infections. PMID- 25135683 TI - Early innate immunity to bacterial infection in the lung is regulated systemically by the commensal microbiota via nod-like receptor ligands. AB - The commensal microbiota is a major regulator of the immune system. The majority of commensal bacteria inhabit the gastrointestinal tract and are known to regulate local mucosal defenses against intestinal pathogens. There is growing appreciation that the commensal microbiota also regulates immune responses at extraintestinal sites. Currently, however, it is unclear how this influences host defenses against bacterial infection outside the intestine. Microbiota depletion caused significant defects in the early innate response to lung infection by the major human pathogen Klebsiella pneumoniae. After microbiota depletion, early clearance of K. pneumoniae was impaired, and this could be rescued by administration of bacterial Nod-like receptor (NLR) ligands (the NOD1 ligand MurNAcTri(DAP) and NOD2 ligand muramyl dipeptide [MDP]) but not bacterial Toll like receptor (TLR) ligands. Importantly, NLR ligands from the gastrointestinal, but not upper respiratory, tract rescued host defenses in the lung. Defects in early innate immunity were found to be due to reduced reactive oxygen species mediated killing of bacteria by alveolar macrophages. These data show that bacterial signals from the intestine have a profound influence on establishing the levels of antibacterial defenses in distal tissues. PMID- 25135684 TI - Homeostasis of N-alpha-terminal acetylation of EsxA correlates with virulence in Mycobacterium marinum. AB - The mycobacterial Esx-1 (ESAT-6 system 1) exporter translocates virulence factors across the cytoplasmic membrane to the cell wall, cell surface, and the bacteriological medium in vitro. The mechanisms underlying substrate targeting to distinct locations are unknown. Several Esx-1 substrates are N-alpha-terminally acetylated. The role of this rare modification in bacteria is unclear. We sought to identify genes required for Esx-1 substrate modification, transport, and localization. Pathogenic mycobacteria lyse Acanthamoeba castellanii in an Esx-1 dependent manner. We conducted a genetic screen to identify Mycobacterium marinum strains which failed to lyse amoebae. We identified a noncytotoxic M. marinum strain with a transposon insertion in a predicted N-alpha-terminal acetyltransferase not previously linked to mycobacterial pathogenesis. Disruption of this gene led to attenuation of virulence, failure to induce a type I interferon response during macrophage infection, and loss of hemolytic activity. The major Esx-1 substrates, EsxA and EsxB, were exported to the cell surface, but only low levels were released into the bacteriological medium. The balance of EsxA N-alpha-terminal acetylation was disrupted, resulting in a mycobacterial strain in which surface-associated EsxA was hyperacetylated. Genetic complementation completely restored Esx-1 function and the levels of N-alpha terminally acetylated EsxA on the surface but restored only low levels of Esx-1 substrates in the bacteriological medium. Our results reveal a novel gene required for mycobacterial Esx-1 export. Our findings indicate that maintaining the homeostasis of Esx-1 substrate N-alpha-terminal acetylation is essential for Esx-1-mediated virulence. We propose an inverse correlation between EsxA acetylation and virulence. PMID- 25135685 TI - Dynamic changes in the Streptococcus pneumoniae transcriptome during transition from biofilm formation to invasive disease upon influenza A virus infection. AB - Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37 degrees C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis. PMID- 25135687 TI - Contributions of NanI sialidase to Caco-2 cell adherence by Clostridium perfringens type A and C strains causing human intestinal disease. AB - Previous studies showed that Clostridium perfringens type D animal disease strain CN3718 uses NanI sialidase for adhering to enterocyte-like Caco-2 cells. The current study analyzed whether NanI is similarly important when type A and C human intestinal disease strains attach to Caco-2 cells. A PCR survey determined that the nanI gene was absent from typical type A food poisoning (FP) strains carrying a chromosomal enterotoxin (CPE) gene or the genetically related type C Darmbrand (Db) strains. However, the nanI gene was present in type A strains from healthy humans, type A strains causing CPE-associated antibiotic-associated diarrhea (AAD) or sporadic diarrhea (SD), and type C Pig-Bel strains. Consistent with NanI sialidase being the major C. perfringens sialidase when produced, FP and Db strains had little supernatant sialidase activity compared to other type A or C human intestinal strains. All type A and C human intestinal strains bound to Caco-2 cells, but NanI-producing strains had higher attachment levels. When produced, NanI can contribute to host cell attachment of human intestinal disease strains, since a nanI null mutant constructed in type A SD strain F4969 had lower Caco-2 cell adhesion than wild-type F4969 or a complemented strain. Further supporting a role for NanI in host cell attachment, sialidase inhibitors reduced F4969 adhesion to Caco-2 cells. Collectively, these results suggest that NanI may contribute to the intestinal attachment and colonization needed for the chronic diarrhea of CPE-associated AAD and SD, but this sialidase appears to be dispensable for the acute pathogenesis of type A FP or type C enteritis necroticans. PMID- 25135686 TI - Lipopolysaccharides belonging to different Salmonella serovars are differentially capable of activating Toll-like receptor 4. AB - Salmonella enterica subsp. enterica serovar (serotype) Abortusovis is a member of the Enterobacteriaceae. This serotype is naturally restricted to ovine species and does not infect humans. Limited information is available about the immune response of sheep to S. Abortusovis. S. Abortusovis, like Salmonella enterica subsp. enterica serovar Typhi, causes a systemic infection in which, under natural conditions, animals are not able to raise a rapid immune response. Failure to induce the appropriate response allows pathogens to reach the placenta and results in an abortion. Lipopolysaccharides (LPSs) are pathogen-associated molecular patterns (PAMPs) that are specific to bacteria and are not synthesized by the host. Toll-like receptors (TLRs) are a family of receptors that specifically recognize PAMPs. As a first step, we were able to identify the presence of Toll-like receptor 4 (TLR4) on the ovine placenta by using an immunohistochemistry technique. To our knowledge, this is the first work describing the interaction between S. Abortusovis LPS and TLR4. Experiments using an embryonic cell line (HEK293) transfected with human and ovine TLR4s showed a reduction of interleukin 8 (IL-8) production by S. Abortusovis and Salmonella enterica subsp. enterica serovar Paratyphi upon LPS stimulation compared to Salmonella enterica subsp. enterica serovar Typhimurium. Identical results were observed using heat-killed bacteria instead of LPS. Based on data obtained with TLR4 in vitro stimulation, we demonstrated that the serotype S. Abortusovis is able to successfully evade the immune system whereas S. Typhimurium and other serovars fail to do so. PMID- 25135689 TI - Closure of a large, persistent enterocutaneous fistula by use of a ventricular septal occluder. PMID- 25135688 TI - Numeracy and literacy independently predict patients' ability to identify out-of range test results. AB - BACKGROUND: Increasing numbers of patients have direct access to laboratory test results outside of clinical consultations. This offers increased opportunities for both self-management of chronic conditions and advance preparation for clinic visits if patients are able to identify test results that are outside the reference ranges. OBJECTIVE: Our objective was to assess whether adults can identify laboratory blood test values outside reference ranges when presented in a format similar to some current patient portals implemented within electronic health record (EHR) systems. METHODS: In an Internet-administered survey, adults aged 40-70 years, approximately half with diabetes, were asked to imagine that they had type 2 diabetes. They were shown laboratory test results displayed in a standard tabular format. We randomized hemoglobin A1c values to be slightly (7.1%) or moderately (8.4%) outside the reference range and randomized other test results to be within or outside their reference ranges (ie, multiple deviations). We assessed (1) whether respondents identified the hemoglobin A1c level as outside the reference range, (2) how respondents rated glycemic control, and (3) whether they would call their doctor. We also measured numeracy and health literacy. RESULTS: Among the 1817 adult participants, viewing test results with multiple deviations increased the probability of identifying hemoglobin A1c values as outside the reference range (participants with diabetes: OR 1.47, 95% CI 1.12-1.92, P=.005; participants without diabetes: OR 1.50, 95% CI 1.13-2.00, P=.005). Both numeracy and health literacy were significant predictors of correctly identifying out-of-range values. For participants with diabetes, numeracy OR 1.32 per unit on a 1-6 scale (95% CI 1.15-1.51, P<.001) and literacy OR 1.59 per unit of a 1-5 scale (95% CI 1.35-1.87, P<.001); for participants without diabetes, numeracy OR 1.36 per unit (95% CI 1.17-1.58, P<.001) and literacy OR 1.33 per unit (95% CI 1.12-1.58, P=.001). Predicted probabilities suggested 77% of higher numeracy and health literacy participants, but only 38% of lower numeracy and literacy participants, could correctly identify the hemoglobin A1c levels as outside the reference range. Correct identification reduced perceived blood glucose control (mean difference 1.68-1.71 points on a 0 10 scale, P<.001). For participants with diabetes, increased health literacy reduced the likelihood of calling one's doctor when hemoglobin A1c=7.1% (OR 0.66 per unit, 95% CI 0.52-0.82, P<.001) and increased numeracy increased intention to call when hemoglobin A1c=8.4% (OR 1.36 per unit, 95% CI 1.10-1.69, P=.005). CONCLUSIONS: Limited health literacy and numeracy skills are significant barriers to basic use of laboratory test result data as currently presented in some EHR portals. Regarding contacting their doctor, less numerate and literate participants with diabetes appear insensitive to the hemoglobin A1c level shown, whereas highly numerate and literate participants with diabetes appear very sensitive. Alternate approaches appear necessary to make test results more meaningful. PMID- 25135690 TI - Arginine Supplementation Induces Arginase Activity and Inhibits TNF-alpha Synthesis in Mice Spleen Macrophages After Intestinal Obstruction. AB - BACKGROUND: The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals. MATERIAL AND METHODS: Male C57BL6/J wild-type (WT) and iNOS knockout (iNOS-/-) mice were randomized into 6 groups: Sham and Sham-/- (standard chow), IO and IO-/- (standard chow + IO), and Arg and Arg-/- (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF-alpha and IL-10 levels were analyzed in splenic macrophage cultures. RESULTS: Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO-/-, and Arg-/- groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF-alpha levels (Arg vs IO group, P < .05) and maintenance of IL-10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines (Sham-/-, IO-/-, and Arg-/- vs other, P < .05). CONCLUSIONS: Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF-alpha levels, which may be directly related to nitric oxide derived from arginine. PMID- 25135691 TI - Cephalotaxus griffithii Hook.f. needle extract induces cell cycle arrest, apoptosis and suppression of hTERT and hTR expression on human breast cancer cells. AB - BACKGROUND: Cephalotaxus spp. are known to possess anticancer potential. In this present work, for the first time the effects of C. griffithii needle (CGN) extracts on human cancer cells were examined. METHODS: The CGN was successively extracted with petroleum ether (PE), acetone and methanol. The extracts were tested for its effect on proliferation of cancer cells (MTT assay on HeLa, ZR751 and HepG2). Extract that showed the maximum growth inhibitory effect was subjected for mechanism of action study. These included apoptosis (morphological and DNA fragmentation assay), cell cycle (flow cytometry), caspase expression (Western blot) and activity (assay kit), p53 (western blot and TP53 siRNA interference) and telomerase expression (reverse transcriptase PCR) analysis. RESULTS: Among the extracts, PE extract induced maximum cytotoxicity, with highest death occurred in ZR751 cells. Since, PE extract induced cell death was highest among the CGN extracts, with maximum cancer cell death occurred in ZR751 cells; we carried out mechanism study of PE extract induced ZR751 cell death. It was observed that PE extract induced ZR751 cell death was associated with cell cycle arrest and apoptosis by activating both intrinsic and extrinsic apoptotic pathways. Knock down study revealed that p53 is essential for loss of ZR751 cell viability induced by PE extract. Further, PE extract down-regulated hTERT, hTR, and c-Myc expression. Thin layer chromatography analysis indicated the presence of unique phytochemicals in PE extract. CONCLUSION: Based on the observations, we concluded that PE extract of C. griffithii needle contains important phyto components with multiple cellular targets for control of breast cancer and is worthy of future studies. PMID- 25135692 TI - CD34(+)CD38(-)CD58(-) cells are leukemia-propagating cells in Philadelphia chromosome-positive acute lymphoblastic leukemia. PMID- 25135693 TI - Mycetoma caused by Nocardia brasiliensis in an immunocompetent patient. PMID- 25135695 TI - Letter from the editor. PMID- 25135694 TI - Ultrasound prediction of perinatal outcome: the unrecognised value of sibling data. AB - OBJECTIVE: To identify high-risk fetuses at the first routinely performed ultrasound examination by making use of information from the mother's previous pregnancy. DESIGN: A population-based cohort study. SETTING: Norway, 1999-2009. POPULATION: All singleton first live births and their second-born siblings registered in the Medical Birth Registry of Norway (166,786 eligible sibling pairs). METHODS: Odds ratios were calculated by logistic regression. MAIN OUTCOME MEASURES: Very small for gestational age (vSGA; birthweight <=-1.96 standard deviations) and perinatal death (stillbirth at >=22 weeks of gestation or death within 28 days of life). RESULTS: Small fetal size at ultrasound (i.e. a fetus smaller than expected by last menstrual period, LMP) is only weakly predictive of vSGA or perinatal death; however, if the firstborn sibling was vSGA at birth, ultrasound measures in the next pregnancy become strongly informative of risk. The smaller the fetal size on ultrasound, the higher its risk of vSGA (3-18%; Ptrend < 0.0001) and perinatal death (4-19 per thousand, Ptrend = 0.012). In contrast, if the first baby was not vSGA, small fetal size on ultrasound is uninformative. CONCLUSIONS: When the firstborn baby is vSGA, discrepancies between fetal size on ultrasound and LMP become highly predictive of risk of vSGA and perinatal mortality in the second-born infant. The value of combining these routinely collected clinical data has not previously been recognised. PMID- 25135696 TI - The role of phakic intraocular lens implants in treatment of high-refractive errors and amblyopia in children. AB - INTRODUCTION: This article aims to evaluate the role of phakic intraocular lens (pIOL) implants in the treatment of high-refractive errors and amblyopia in the pediatric setting. METHODS: A literature search of the PubMed database was conducted in December 2012 using the keywords: pIOL implants, amblyopia, pediatric refractive surgery and ametropia, and articles of high or medium clinical relevance were selected for review. Inclusion criteria were children aged 0-17 years who had undergone pIOL implantation for the treatment of refractive errors and/or amblyopia. RESULTS: Multiple studies have shown the relevancy and effectiveness of pIOL implantation as an alternative surgical management for highly significant pediatric ametropia in selective patients who are noncompliant with medical treatment. CONCLUSIONS: In the management of clinically significant severe pediatric ametropic and/or anisometropic myopia or hyperopia and in the event of nonadherence to traditional medical treatment, phakic anterior chamber IOL implantation is currently considered an effective modality of treatment. Long-term follow-up of pediatric patients following pIOL implantation is necessary. Future clinical trials are needed to address the safety and efficacy of the type of and the best time for pIOL implantation in treatment and/or prevention of amblyopia in children. PMID- 25135697 TI - Observation of peripheral retina by topical endoscopic imaging method-a preliminary study. AB - INTRODUCTION: This study evaluated the usefulness of rigid endoscopy placed on the corneal surface to observe the peripheral retina. METHODS: The authors studied 15 eyes in 15 patients (12 men, 3 women; mean age 55.9 years; range 22-74 years) that underwent vitreous surgery at the Department of Ophthalmology at Saga University Hospital. With patients in a supine position, after topical anesthesia, an eye cup was placed between the eyelids and filled with hydroxyethyl cellulose solution and physiologic saline. With a rigid endoscope placed near the corneal surface, the target areas were then observed and recorded. The usefulness of rigid endoscopy to observe the peripheral retina was evaluated based on differences due to lens status and pupil size. RESULTS: In seven aphakic eyes, irrespective of pupil size, the peripheral retina could be observed up to the entire ora serrata (all quadrants). In eight eyes implanted with an intraocular lens, the observable area changed with pupil size and anterior capsulorrhexis size. CONCLUSION: This technique using rigid endoscopy was simple to manipulate and useful for observing and recording the peripheral retina. In particular, in aphakic eyes, irrespective of pupil size, the retina could be observed to the ora serrata. PMID- 25135698 TI - Evaluation of retinal nerve fiber layer changes with oral isotretinoin treatment. AB - INTRODUCTION: Central nervous system toxicity is a well-known side effect of isotretinoin treatment. The aim of this study was to establish the effects of isotretinoin on retinal nerve fiber layer (RNFL) thickness. MATERIALS AND METHODS: Study subjects received oral isotretinoin treatment for nodulocystic acne. All patients underwent a detailed ophthalmologic examination including best corrected visual acuity, slit-lamp examination, tonometry, color vision assessment, fundoscopy, and RNFL measurement. RNFL measurements by optical coherence tomography were done at onset, and were repeated at the 1st and 6th months of therapy. RESULTS: A total of 22 eyes of 11 patients (seven males and four females) were included in this study. The mean age of the patients was 20.18 +/- 5.13 (14-26) years. Mean RNFL thickness was 90.72 +/- 9.19 (78.2-112.0) MUm before treatment, 90.40 +/- 9.24 (79.5-112.4) MUm after 1 month of treatment, and 90.52 +/- 8.92 (78.4-114.8) MUm after 6 months. No statistically significant change was detected between RNFL thickness values before and after treatment. CONCLUSION: No adverse effects of systemic isotretinoin treatment on RNFL thickness were observed. PMID- 25135699 TI - Transcorneal electrical stimulation in patients with retinal artery occlusion: a prospective, randomized, sham-controlled pilot study. AB - INTRODUCTION: The purpose of this study was to investigate the safety and efficacy of transcorneal electrical stimulation (TES) in patients suffering from retinal artery occlusion (RAO). METHODS: Twelve patients with central and one patient with branch RAO (age 25-84 years, median 74 years) were enrolled in this prospective, randomized, sham-controlled study. RAO was diagnosed 10 days to 17 months prior to study participation. Patients were treated with TES (5 ms positive followed by 5 ms negative biphasic pulses at 20 Hz; applied with DTL electrodes) for 30 min once a week for 6 consecutive weeks. Patients were randomly assigned to TES with 0 mA (sham, n = 3), 66% (n = 5) or 150% (n = 5) of the patient's individual electrical phosphene threshold (EPT) at 20 Hz. Best corrected visual acuity, ophthalmology examination and EPT (at 3, 6, 9, 20, 40, 60, and 80 Hz) were determined at baseline and at eight follow-up visits over 17 weeks. During four visits (week 1, 5, 9, and 17) kinetic and static visual fields as well as full-field and multifocal electroretinography were measured. The method of restricted maximum likelihood (P < 0.05, Tukey-Kramer) was used to estimate the development of parameters under treatment. RESULTS: TES was tolerated well; no ocular or systemic adverse events were observed except for foreign-body sensation after TES (n = 3). During the study period the slopes of the scotopic a-wave increased significantly (high-intensity flash white 10 cd.s/m(2); P = 0.03) in the 150% treatment group. All other parameters in all other groups remained statistically unchanged. CONCLUSIONS: Although TES was tolerated well, statistically significant improvements were found only for specific a-wave slopes. This is in contradiction to previous smaller, uncontrolled reports. Further studies with larger sample sizes and longer duration might, however, show additional significant effects. PMID- 25135701 TI - Erratum to: Topical Isopropyl Unoprostone for Retinitis Pigmentosa: Microperimetric Results of the Phase 2 Clinical Study. PMID- 25135700 TI - Vascular endothelial growth factor in anterior chamber liquid patients with diabetic retinopathy, cataract and neovascular glaucoma. AB - INTRODUCTION: The aims of this study were: (1) to investigate the association of vascular endothelial growth factor isoform A (VEGF-A) concentration in the anterior chamber liquid (ACL) with vascular proliferation in patients with diabetic retinopathy (DR) who had undergone surgical treatment for cataract and neovascular glaucoma; (2) to analyze the association of VEGF-A level in ACL with the cataract surgery outcomes. MATERIALS AND METHODS: Undiluted aqueous fluid samples were obtained from 207 eyes of patients who underwent intraocular surgery, 136 patients with diabetes mellitus (DM) and 22 patients without DM. The ACL samples were obtained during operation. The VEGF-A levels were analyzed by enzyme-linked immunosorbent assay. RESULTS: The lowest VEGF-A levels were in diabetic patients without signs of DR [22.75 pg/mL (10.78; 63.36)]. More severe DR tended to occur in diabetic patients with higher VEGF-A levels in ACL. In diabetic patients with proliferative DR (PDR), VEGF-A levels were significantly higher [336.6 pg/mL (232.3; 410.74)] than in patients without DR P < 0.0001. In patients with terminal stage of DR [neovascular glaucoma (NG)], VEGF-A levels were dramatically higher and attained 1,634.01 pg/mL (610.69; 2657.33). In non diabetic patients, VEGF-A levels were 95.07 pg/ml (60.92; 129.22). The best visual acuity results in post-operative period were observed in the group of diabetic patients without DR. In the group of patients with PDR, post-operative visual acuity [0.26 (0.1; 0.42)] was similar to visual acuity before operation [0.29 (0.13; 0.44)]. There was no significant increase in visual acuity due to cataract surgery. In 52.4% patients, no complications had occurred by the end of the follow-up period. In 40% patients, retinal laser coagulation was performed, and in 7.6% patients NG had developed. CONCLUSION: VEGF-A level in ACL increases with DR progression and may be of prognostic value in evaluating the potential risk of further neovascularization progression in diabetic patients. PMID- 25135702 TI - Screening methodologies for the development of spray-dried amorphous solid dispersions. AB - PURPOSE: To present a new screening methodology intended to be used in the early development of spray-dried amorphous solid dispersions. METHODS: A model that combines thermodynamic, kinetic and manufacturing considerations was implemented to obtain estimates of the miscibility and phase behavior of different itraconazole-based solid dispersions. Additionally, a small-scale solvent casting protocol was developed to enable a fast assessment on the amorphous stability of the different drug-polymer systems. Then, solid dispersions at predefined drug loads were produced in a lab-scale spray dryer for powder characterization and comparison of the results generated by the model and solvent cast samples. RESULTS: The results obtained with the model enabled the ranking of the polymers from a miscibility standpoint. Such ranking was consistent with the experimental data obtained by solvent casting and spray drying. Moreover, the range of optimal drug load determined by the model was as well consistent with the experimental results. CONCLUSIONS: The screening methodology presented in this work showed that a set of amorphous formulation candidates can be assessed in a computer model, enabling not only the determination of the most suitable polymers, but also of the optimal drug load range to be tested in laboratory experiments. The set of formulation candidates can then be further fine-tuned with solvent casting experiments using a small amount of API, which will then provide the decision for the final candidate formulations to be assessed in spray drying experiments. PMID- 25135703 TI - [Aggravated reduction of the posterior malleolar fracture due to incarceration of the flexor digitorum longus tendon]. AB - The indications for stabilization of the posterior malleolus (Volkmann triangle) while fixing ankle fractures are controversially discussed. Detailed descriptions of possible obstacles to reduction are scarce. The following case describes the difficulty of reduction of the posterior malleolus caused by interposition of the flexor digitorum longus tendon. The fracture line of the posterior malleolus passed in an atypical manner vertically to the posterior-medial tibial margin with direct contact to the anatomical pathway of the tendon. The impaction of the tendon was already present in the computed tomography (CT) scan taken preoperatively but the tendon hindering malleolar reduction was first realized during surgery after several unsuccessful attempts at repositioning. PMID- 25135704 TI - [Expectations from the TraumaNetwork DGU(r): Which goals have been achieved? What can be improved?]. AB - INTRODUCTION: Following the establishment of the first trauma networks in 2009 an almost nationwide certification could be achieved. Despite the impressive number of 46 certified networks, little is known about the actual improvements and the satisfaction of the participating hospitals. OBJECTIVES: This article aims to give a first representative overview of the expectations and actual achievements. MATERIAL AND METHODS: An online survey with a total of 36 questions was conducted in 884 hospitals. The questionnaire could be filled out online, sent by post or fax to the AKUT- Office. Descriptive statistical analyses were performed with Microsoft Excel. RESULTS: With 326 responses, a response rate of 48.9% of all active hospitals was achieved. Of the participating hospitals 64.1% (209) were certified and had taken part in the project for an average of 3.9 years. The average score for satisfaction was 2.3, 72.4% (236) felt that there was a need for improvement in the care of severely injured patients and 46.6% (152) in the transfer of patients. In 47.2% (142) no improvement in cooperation with the ambulance service could be determined, 25.2% (82) documented an increase in the number of severely injured patients since participating in the trauma network (TNW-DGU) and 93.9% (306) of all hospitals wanted to participate in the trauma network in the future. DISCUSSION: It could be shown that important goals, such as simplification of patient transfer or general improvement in cooperation have been achieved. Overall there was a high level of satisfaction among the participating hospitals; however, the survey has identified some points which need to be improved by further intensive work. PMID- 25135705 TI - [Aseptic acetabular necrosis with recurrent luxation of a bipolar hemiarthroplasty into the retroperitoneum]. AB - In comparison to aseptic osteonecrosis of the femoral head, the occurrence of aseptic acetabular osteonecrosis is extremely rare. This article reports the case of a 77-year-old woman with a large defect of the posterior acetabular wall (type 3 AAOS/D'Antonio score). We present an option for treatment in cases of a combination of osteonecrosis with implanted bipolar hemiarthroplasty. PMID- 25135706 TI - [Bilateral carotid artery dissection in a kite surfer by strangulation with the kite lines]. AB - While a kite surfer was preparing the kite it was caught by a gust of wind, which blew it 10 m into the air and the cords became entangled around the neck of the kite surfer causing strangulation. After admittance to hospital, the diagnostics revealed multiple injuries including a bilateral dissection of the internal carotid arteries, cerebral edema and multiple fractures. As kitesurfing is gaining popularity severe injuries are becoming more frequent. Safety precautions, such as preparing the kite with two persons, wearing safety equipment and using bars with a safety leash can prevent severe injuries. PMID- 25135707 TI - [Out-of-hospital airway management in trauma patients : Experiences with the C MAC(r) video laryngoscope]. AB - BACKGROUND: Securing the airway is the top priority in trauma resuscitation. The most important factor for successful endotracheal intubation (ETI) is good visualization of the vocal cords. The aim of this study was to summarize the practical experiences with the C-MAC(r) video laryngoscope as initial device in out-of-hospital airway management of trauma patients. METHODS: The C-MAC(r) video laryngoscope uses standard Macintosh shaped laryngoscope blades. At the Helicopter Emergency Medical Service (HEMS) Christoph 22 it is used as the initial device for every out-of-hospital ETI. All prehospital data on ETI involving trauma patients were documented for a period of 17 months. RESULTS: A total of 116 out-of-hospital ETIs were enrolled in this study (overall success rate 100 %). In 88.8 % the first attempt was successful, whereas in 10.3 % a second and in 0.9 % a third ETI attempt was necessary. No patient required alternative airway devices or surgical airway interventions. The results of a subgroup with an immobilized cervical spine (n = 17) did not show any increased difficulties. CONCLUSION: The use of the C-MAC(r) video laryngoscope by experienced anesthesiologists in an out-of-hospital setting seems to be a safe method even in patients with an immobilized cervical spine. Adverse laryngoscopy results (C/L III and IV) were reduced compared to other studies. PMID- 25135710 TI - A scoping review of time-use research in occupational therapy and occupational science. AB - BACKGROUND: Time use is a defining interest within occupational therapy and occupational science. This is evident through the range of contributions to the disciplinary knowledge base. Indeed it has been suggested that time-use methods are amongst the most established research techniques used to explore aspects of human occupation. However, the extent and nature of such activity in occupational therapy and occupational science has not been examined to date. AIM: This study sought to map the extent and nature of time-use research in occupational therapy and occupational science journals and the extent to which studies explored the relationship between time-use and health. METHOD: A scoping review method was used. RESULTS: Sixty-one studies were included. Scandinavian countries contributed the largest number of studies (n = 16, 26%). While time-use diaries were used most frequently (n = 30, 49%) occupational therapists and occupational scientists have developed a range of data-collection instruments. Forty-nine studies (80%) focused on time-use in clinical or defined population sub-groups. Ten studies (16%) included an empirical examination of the relationship between time-use and health. CONCLUSION: Future research should examine time-use and health amongst well populations across the lifespan and in different parts of the world. PMID- 25135708 TI - Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress in a mouse model of Alzheimer's disease. AB - The role of mitochondrial dysfunction and oxidative stress has been well documented in Alzheimer's disease (AD). Bioflavonoids are being utilised as neuroprotectants in the treatment of various neurological disorders, including AD. Therefore, we conducted this current study in order to explore the effects of hesperidin (a flavanone glycoside) against amyloid-beta (Abeta)-induced cognitive dysfunction, oxidative damage and mitochondrial dysfunction in mice. Three-month old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two hesperidin (either 50 or 100 mg/kg per day) groups, or an Aricept (2.5 mg/kg per day) group. After 16 weeks of treatment, although there was no obvious change in Abeta deposition in the hesperidin-treated (100 mg/kg per day) group, however, we found that the administration of hesperidin (100 mg/kg per day) resulted in the reduction of learning and memory deficits, improved locomotor activity, and the increase of anti-oxidative defense and mitochondrial complex I-IV enzymes activities. Furthermore, Glycogen synthase kinase-3beta (GSK-3beta) phosphorylation significantly increased in the hesperidin-treated (100 mg/kg per day) group. Taken together, these findings suggest that a reduction in mitochondrial dysfunction through the inhibition of GSK-3beta activity, coupled with an increase in anti-oxidative defense, may be one of the mechanisms by which hesperidin improves cognitive function in the APPswe/PS1dE9 transgenic mouse model of AD. PMID- 25135709 TI - Inhibition of akt phosphorylation diminishes mitochondrial biogenesis regulators, tricarboxylic acid cycle activity and exacerbates recognition memory deficit in rat model of Alzheimer's disease. AB - 3-Methyladenine (3-MA), as a PI3K inhibitor, is widely used for inhibition of autophagy. Inhibition of PI3K class I leads to inhibition of Akt phosphorylation, a central molecule involved in diverse arrays of intracellular cascades in nervous system. Accordingly, in the present study, we aimed to determine the alterations of specific mitochondrial biogenesis markers and mitochondrial function in 3-MA-injected rats following amyloid beta (Abeta) insult. Our data revealed that inhibition of Akt phosphorylation downregulates master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha). Our data also showed that decrease in PGC 1alpha level presumably is due to decrease in the phosphorylation of cAMP response element binding and AMP-activated kinase, two upstream activators of PGC 1alpha. As a consequence, the level of some mitochondrial biogenesis factors including nuclear respiratory factor-1, mitochondrial transcription factor A, and Cytochrome c decreased significantly. Also, activities of tricarboxylic acid cycle (TCA) enzymes such as Aconitase, a-ketoglutarate dehydrogenase, and malate dehydrogenase reduced in the presence of 3-MA with or without Abeta insult. Decrease in mitochondrial biogenesis factors and TCA enzyme activity in the rats receiving 3-MA and Abeta were more compared to the rats that received either alone; indicating the additive destructive effects of these two agents. In agreement with our molecular results, data obtained from behavioral test (using novel objective recognition test) indicated that inhibition of Akt phosphorylation with or without Abeta injection impaired novel recognition (non spatial) memory. Our results suggest that 3-MA amplified deleterious effects of Abeta by targeting central molecule Akt. PMID- 25135711 TI - Comparison of diagnostic performance of CT and MRI for abdominal staging of pediatric renal tumors: a report from the Children's Oncology Group. AB - BACKGROUND: CT and MRI are both used for abdominal staging of pediatric renal tumors. The diagnostic performance of the two modalities for local and regional staging of renal tumors has not been systematically evaluated. OBJECTIVE: To compare the diagnostic performance of CT and MRI for local staging of pediatric renal tumors. MATERIALS AND METHODS: The study population was derived from the AREN03B2 study of the Children's Oncology Group. Baseline abdominal imaging performed with both CT and MRI within 30 days of nephrectomy was available for retrospective review in 82 renal tumor cases. Each case was evaluated for capsular penetration, lymph node metastasis, tumor thrombus, preoperative tumor rupture, and synchronous contralateral lesions. The surgical and pathological findings at central review were the reference standard. RESULTS: The sensitivity of CT and MRI for detecting capsular penetration was 68.6% and 62.9%, respectively (P = 0.73), while specificity was 86.5% and 83.8% (P = 1.0). The sensitivity of CT and MRI for detecting lymph node metastasis was 76.5% and 52.9% (P = 0.22), and specificity was 90.4% and 92.3% (P = 1.0). Synchronous contralateral lesions were identified by CT in 4/9 cases and by MRI in 7/9 cases. CONCLUSION: CT and MRI have similar diagnostic performance for detection of lymph node metastasis and capsular penetration. MR detected more contralateral synchronous lesions; however these were present in a very small number of cases. Either modality can be used for initial loco-regional staging of pediatric renal tumors. PMID- 25135712 TI - Decolonization with Mupirocin and Subsequent Risk of Methicillin-Resistant Staphylococcus aureus Carriage in Veterans Affairs Hospitals. AB - INTRODUCTION: Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections remain one of the leading causes of preventable patient mortality in the US. Eradication of MRSA through decolonization could prevent both MRSA infections and transmission; however, there is currently no consensus within the infectious disease community on the proper role of decolonization in the prevention of infections. The purpose of this study was to assess the impact of decolonization with mupirocin on subsequent MRSA carriage. METHODS: Patients included in this study were those with an inpatient admission to a Department of Veterans Affairs (VA) hospital between January 1, 2008 and December 31, 2009 who had a positive MRSA screen on admission and a subsequent re-admission during the same time period. Exposure to mupirocin on the initial hospital admission was measured using Barcode Medication Administration data and MRSA carriage was measured using microbiology text reports and lab data containing results from surveillance swabs collected from the nares. Chi-square tests were used to test for differences in re-admission MRSA carriage rates between mupirocin-receiving and non-mupirocin-receiving patients. RESULTS: Of the 25,282 MRSA-positive patients with a subsequent re-admission included in the present study cohort, 1,183 (4.7%) received mupirocin during their initial hospitalization. Among the patients in the present study cohort who were re-admitted within 30 days, those who received mupirocin were less likely to test positive for MRSA carriage than those who did not receive mupirocin (27.2% vs. 55.1%, P < 0.001). The proportion of those who tested positive for MRSA during re-admissions that occurred 30-60 days, 60-120 days, and >120 days were 33.9, 37.3, and 41.0%, respectively, among mupirocin patients and 52.7%, 53.0%, and 51.9%, respectively, for patients who did not receive mupirocin (P < 0.001 at each time point). CONCLUSION: Patients decolonized with mupirocin in VA hospitals were less likely to be colonized with MRSA on re-admission as long as 4 months after decolonization. PMID- 25135714 TI - Effect of uric-acid-lowering therapy on progression of chronic kidney disease: a meta-analysis. AB - The efficacy and safety of uric-acid-lowering therapy (UALT) on slowing the progression of chronic kidney disease (CKD) accompanied by hyperuricemia were assessed. We searched Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases up to November 15, 2012 for randomized controlled trials (RCTs) which compared the effect of UALT to control therapy in hyperuricemic patients secondary to CKD, and then performed quality evaluation and meta-analysis on the included studies. Seven RCTs involving 451 cases were included. UALT delayed the increase of serum creatinine (MD=-62.55 MUmol/L, 95% CI: -98.10 to -26.99) and blood urea nitrogen (MD= -6.15 mmol/L, 95% CI: -8.17 to -4.13) as well as the decrease of glomerular filtration rate [MD=5.65 mL/(min.1.73 m2), 95% CI: 1.88 to 9.41], decreased systolic blood pressure (SBP) (MD= -6.08 mmHg, 95% CI: -11.67 to -0.49), and reduced the risk of the renal disease progression (RR=0.30, 95% CI: 0.19 to 0.46). However, there was no statistically significant difference in 24-h urinary protein quantity and diastolic blood pressure (P>0.05). We identified that UALT could delay the progression of CKD with secondary hyperuricemia. And this also indirectly proved that hyperuricemia was a risk factor for the CKD progression. PMID- 25135713 TI - Diagnosis and treatment of cholangiocarcinoma: a consensus from surgical specialists of China. PMID- 25135716 TI - Expression and clinical significance of Semaphorin4D in non-small cell lung cancer and its impact on malignant behaviors of A549 lung cancer cells. AB - This study aimed to explore Semaphrin4D (Sema4D) expression and clinical significance in non-small cell lung cancer (NSCLC), and to define the roles and mechanisms of Sema4D in regulating the malignant behaviors of A549 cells by small interfering RNA (siRNA). Firstly, immunohistochemistry revealed that Sema4D was more frequently expressed in NSCLC than in lung benign lesion (P<0.05) and its overexpression was associated with low differentiation (P<0.05), poor pTNM staging (P<0.05) and occurrence of lymph node (LN) metastasis (P<0.05). Endogenous Sema4D expression was suppressed by Sema4D siRNA in A549 cells overexpressing Sema4D. Protein levels of Sema4D, total Akt and p-Akt were examined by Western blotting. Cell proliferation, migration and invasion abilities were measured by MTT assay and Transwell assay respectively. Results showed that Sema4D siRNA significantly suppressed phosphorylation of AKT in A549 cells, but it did not alter total AKT expression. In addition, efficient down regulation of SemaD significantly inhibit cell proliferation (P<0.05), migration (P<0.05) and invasion (P<0.05) in A549 cells. These findings suggest that Sema4D might serve as a reliable tool for early prediction of NSCLC poor prognosis. Sema4D could play an important role in promoting tumor proliferation, migration and metastasis in the NSCLC, by influencing the Akt protein phosphorylation. Inhibition of Sema4D may be a useful approach for the treatment of NSCLC. PMID- 25135715 TI - Differential effect of calcium-activated potassium and chloride channels on rat basilar artery vasomotion. AB - Spontaneous, rhythmical contractions, or vasomotion, can be recorded from cerebral vessels under both normal physiological and pathophysiological conditions. We investigated the cellular mechanisms underlying vasomotion in the cerebral basilar artery (BA) of Wistar rats. Pressure myograph video microscopy was used to study the changes in cerebral artery vessel diameter. The main results of this study were as follows: (1) The diameters of BA and middle cerebral artery (MCA) were 314.5+/-15.7 MUm (n=15) and 233.3+/-10.1 MUm (n=12) at 10 mmHg working pressure (P<0.05), respectively. Pressure-induced vasomotion occurred in BA (22/28, 78.6%), but not in MCA (4/31, 12.9%) from 0 to 70 mmHg working pressure. As is typical for vasomotion, the contractile phase of the response was more rapid than the relaxation phase; (2) The frequency of vasomotion response and the diameter were gradually increased in BA from 0 to 70 mmHg working pressure. The amplitude of the rhythmic contractions was relatively constant once stable conditions were achieved. The frequency of contractions was variable and the highest value was 16.7+/-4.7 (n=13) per 10 min at 60 mmHg working pressure; (3) The pressure-induced vasomotion of the isolated BA was attenuated by nifedipine, NFA, 18beta-GA, TEA or in Ca(2+)-free medium. Nifedipine, NFA, 18beta-GA or Ca(2+)-free medium not only dampened vasomotion, but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction state. These results suggest that the pressure-induced vasomotion of the isolated BA results from an interaction between Ca(2+)-activated Cl(-) channels (CaCCs) currents and K(Ca) currents. We hypothesize that vasomotion of BA depends on the depolarizing of the vascular smooth muscle cells (VSMCs) to activate CaCCs. Depolarization in turn activates voltage-dependent Ca(2+) channels, synchronizing contractions of adjacent cells through influx of extracellular calcium and the flow of calcium through gap junctions. Subsequent calcium-induced calcium release from ryanodine-sensitive stores activates K(Ca) channels and hyperpolarizes VSMCs, which provides a negative feedback loop for regenerating the contractile cycle. PMID- 25135717 TI - Anticancer effect of icaritin on human lung cancer cells through inducing S phase cell cycle arrest and apoptosis. AB - Icaritin, a prenylflavonoid derivative from Epimedium Genus, has been shown to exhibit many pharmacological and biological activities. However, the function and the underlying mechanisms of icaritin in human non-small cell lung cancer have not been fully elucidated. The purpose of this study was to investigate the anticancer effects of icaritin on A549 cells and explore the underlying molecular mechanism. The cell viability after icaritin treatment was tested by MTT assay. The cell cycle distribution, apoptosis and reactive oxygen species (ROS) levels were analyzed by flow cytometry. The mRNA and protein expression levels of the genes involved in proliferation and apoptosis were respectively detected by RT PCR and Western blotting. The results demonstrated that icaritin induced cell cycle arrest at S phase, and down-regulated the expression levels of S regulatory proteins such as Cyclin A and CDK2. Icaritin also induced cell apoptosis characterized by positive Hoechst 33258 staining, accumulation of the Annexin V positive cells, increased ROS level and alteration in Bcl-2 family proteins expression. Moreover, icaritin induced sustained phosphorylation of ERK and p38 MAPK. These findings suggested that icaritin might be a new potent inhibitor by inducing S phase arrest and apoptosis in human lung carcinoma A549 cells. PMID- 25135718 TI - Effect of TRPV1 channel on proliferation and apoptosis of airway smooth muscle cells of rats. AB - Airway remodeling is an important pathological feature of asthma and the basis of severe asthma. Proliferation of airway smooth muscle cells (ASMCs) is a major contributor to airway remodeling. As an important Ca(2+) channel, transient receptor potential vanilloid 1 (TRPV1) plays the key role in the cell pathological and physiological processes. This study investigated the expression and activity of TRPV1 channel, and further clarified the effect of TRPV1 channel on the ASMCs proliferation and apoptosis in order to provide the scientific basis to treat asthmatic airway remodeling in clinical practice. Immunofluorescence staining and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the expression of TRPV1 in rat ASMCs. Intracellular Ca(2+) was detected using the single cell confocal fluorescence microscopy measurement loaded with Fluo-4/AM. The cell cycles were observed by flow cytometry. MTT assay and Hoechst 33258 staining were used to detect the proliferation and apoptosis of ASMCs in rats respectively. The data showed that: (1) TRPV1 channel was present in rat ASMCs. (2) TRPV1 channel agonist, capsaicin, increased the Ca(2+) influx in a concentration-dependent manner (EC50=284.3+/-58 nmol/L). TRPV1 channel antagonist, capsazepine, inhibited Ca(2+) influx in rat ASMCs. (3) Capsaicin significantly increased the percentage of S+G2M ASMCs and the absorbance of MTT assay. Capsazepine had the opposite effect. (4) Capsaicin significantly inhibited the apoptosis, whereas capsazepine had the opposite effect. These results suggest that TRPV1 is present and mediates Ca(2+) influx in rat ASMCs. TRPV1 activity stimulates proliferation of ASMCs in rats. PMID- 25135719 TI - Changes of neuronal activities after gut electrical stimulation with different parameters and locations in lateral hypothalamus area of obese rats. AB - This study tested the effects of the gastrointestinal pulse train electrical stimulation with different parameters and at different locations on the neuronal activities of the lateral hypothalamus area (LHA) in obese rats in order to find the optimal stimulation parameter and location. Eight gastric electrical stimulations (GES) with different parameters were performed and the neuronal activities of gastric-distension responsive (GD-R) neurons in LHA were observed. The effects of stimulations with 8 parameters were compared to find the optimal parameter. Then the optimal parameter was used to perform electrical stimulation at duodenum and ileum, and the effects of the duodenal and ileac stimulation on the GD-R neurons in LHA were compared with the gastric stimulation of optimal parameter. The results showed that GES with the lowest energy parameter (0.3 ms, 3 mA, 20 Hz, 2 s on, 3 s off) activated the least neurons. The effects of GES with other parameters whose pulse width was 0.3 ms were not significantly different from those of the lowest energy parameter. Most gastric stimulations whose pulse width was 3 ms activated more LHA neurons than the smallest energy parameter stimulation, and the effects of those 3 ms gastric stimulations were similar. Accordingly, the lowest energy parameter was recognized as the optimal parameter. The effects of stimulations with the optimal parameter at stomach, duodenum and ileum on the LHA neuronal activities were not different. Collectively, gastrointestinal electrical stimulation (GIES) with relatively large pulse width might have stronger effects to the neuronal activities of GD-R neurons in LHA of obese rats. The effects of the GIES at different locations (stomach, duodenum and ileum) on those neurons are similar, and GES is preferential because of its easy clinical performance and safety. PMID- 25135720 TI - Glucocorticoid receptor agonist dexamethasone attenuates renal ischemia/reperfusion injury by up-regulating eNOS/iNOS. AB - The aim of this study was to determine the effect of dexamethasone (DEX) on renal ischemia/reperfusion injury (IRI). C57BL/6 mice were randomly divided into Sham group, IRI group and DEX group. The mice in IRI and DEX groups subjected to renal ischemia for 60 min, were treated with saline or DEX (4 mg/kg, i.p.) 60 min prior to I/R. After 24 h of reperfusion, the renal function, renal pathological changes, activation of extracellular signal-regulated kinase (ERK) and glucocorticoid receptor (GR), and the levels of iNOS and eNOS were detected. The results showed DEX significantly decreased the damage to renal function and pathological changes after renal IRI. Pre-treatment with DEX reduced ERK activation and down-regulated the level of iNOS, whereas up-regulated the level of eNOS after renal IRI. DEX could further promote the activation of GR. These findings indicated GR activation confers preconditioning-like protection against acute IRI partially by up-regulating the ratio of eNOS/iNOS. PMID- 25135721 TI - Anti-cancer effects of novel doxorubicin prodrug PDOX in MCF-7 breast cancer cells. AB - Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to decrease toxicities while maintaining the potent anticancer effects of DOX. This study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21 signaling alterations were studied. Abundant cathepsin B was found in the MCF-7 cells, and treatment with PDOX and DOX triggered dose- and time-dependent cytotoxicity and resulted in a significant reduction in cell viability. The IC50 of PDOX and DOX was 3.91 and 0.94 MUmol/L, respectively. Both PDOX and DOX caused an up-regulation of the P53/P21-related signal pathway, and PDOX significantly increased expression of P53 and caspase 3, and arrested the cell cycle at the G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have different action mechanisms on breast cancer cells. PMID- 25135722 TI - Antitumor activity of recombinant antimicrobial peptide penaeidin-2 against kidney cancer cells. AB - Penaeidin-2 (Pen-2) is an important antimicrobial peptide derived from the Pacific white shrimp, Penaeus vannamei, and possesses both antibacterial and antifungal activities. Recent studies suggest that recombinant penaeidins show similar activities to the native Pen-2 protein. Previous researches have shown that some antimicrobial peptides (AMPs) exhibit cytotoxic activity against cancer cells. To date, there have been no studies on the antitumor effects of Pen-2. This study evaluated the potential of recombinant pen-2 (rPen-2) in the selective killing of kidney cancer cell lines ACHN and A498, and its action mechanism. MTT assays found the maximal growth inhibition of HK-2, ACHN and A498 cells treated with 100 MUg/mL rPen-2 at 48 h was 13.2%, 62.4%, and 70.4%, respectively. DNA specific fluorescent dye staining showed a high percentage of apoptosis on cancer cells. Flow cytometry revealed that the apoptosis rate of HK-2, ACHN and A498 cells was 15.2%, 55.2%, and 61.5% at 48 h respectively, suggesting that rPen-2 induced higher apoptosis rate in cancer cells than in HK-2 cells. Laser confocal scanning microscopy demonstrated that the plasma membrane was the key site where rPen-2 interacted with and destroyed tumor cells. Scanning electron microscopy showed the morphologic changes of the cell membranes of kidney cancer cells treated with rPen-2. These results suggest that rPen-2 is a novel potential therapeutic agent that may be useful in treating kidney cancers. PMID- 25135724 TI - Combination therapy with pegylated interferon alpha-2b and adefovir dipivoxil in HBeAg-positive chronic hepatitis B versus interferon alone: a prospective, randomized study. AB - Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B (CHB). The objective of the present study was to compare the efficacy and safety of pegylated interferon (Peg-IFN) alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg IFN alpha-2b alone (1.5 MUg/kg once weekly) or Peg-IFN alpha-2b plus adefovir (10 mg daily) for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30 (36.7%) patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31 (25.8%) in the monotherapy group (P=0.36). In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group (76.7% vs. 29.0%, P<0.001). Thyroid dysfunction was more frequent in the combination group than in the monotherapy group (P<0.05). In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function. PMID- 25135723 TI - Over-expression of testis-specific expressed gene 1 attenuates the proliferation and induces apoptosis of GC-1spg cells. AB - The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on the viability and apoptosis of cultured spermatogonial GC-1spg cells were investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053TM) was obtained as the cell model in order to explore the function of TSEG-1. We transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase. Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and reduced the mitochondrial membrane potential of GC-1spg cells. Moreover, transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and transcript levels of caspase 9, and decreased the expression of Fas and caspase 8 in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses the proliferation and induces the apoptosis of GC-1spg cells, which establishes a basis for further study on the function of TSEG-1. PMID- 25135725 TI - Expression profiling of microRNAs in hippocampus of rats following traumatic brain injury. AB - The changes of microRNA expression in rat hippocampus after traumatic brain injury (TBI) were explored. Adult SD rats received a single controlled cortical impact injury, and the ipsilateral hippocampus was harvested for the subsequent microarray assay at three time points after TBI: 1st day, 3rd day and 5th day, respectively. We characterized the microRNA expression profile in rat hippocampus using the microRNA microarray analysis, and further verified microarray results of miR-142-3p and miR-221 using quantitative real-time PCR. Totally 205 microRNAs were identified and up-/down-regulated more than 1.5 times. There were significant changes in 17 microRNAs at all three time points post-TBI. The quantitative real-time PCR results of miR-142-3p and miR-221 indicated good consistency with the results of the microarray method. MicroRNAs altered at different time points post-TBI. MiR-142-3p and miR-221 may be used as potentially biological markers for TBI assessment in forensic practice. PMID- 25135726 TI - E-cadherin-transfected neural stem cells transplantation for spinal cord injury in rats. AB - The effects of E-cadherin-transfected neural stem cells (NSCs) transplantation for spinal cord injury (SCI) in rats were investigated. Sixty SD rats were randomly divided into model control group, NSCs group, empty plasmid group and E cadherin overexpression group (n=15 each). The animal SCI model was established by using the modified Allen's method. NSCs were cultured. Rats in NSCs group were subjected to NSCs transplantation. E-cadherin gene eucaryotic expression vector and pcDNA3.1-E-cadherin were respectively transfected into cultured NSCs, serving as empty plasmid group and E-cadherin overexpression group respectively. At 7th day after transplantation, neurological function of all rats was assessed by Tarlov score. After rats were sacrificed in each group, the number of BrdU and Nestin positive cells was counted by immunohistochemistry. Immumofluorescence method was used to detect the expression of neurofilament protein (NF) and glial fibrillary acidic protein (GFAP). As compared with model control group, the Tarlov score and the number of of BrdU and Nestin positive cells, and the expression of NF and GFAP in NSCs group, empty plasmid group, and E-cadherin overexpression group were increased significantly (P<0.05), and those in the E cadherin overexpression group were increased more significantly than the other transplantation groups (P<0.05). It was suggested that E-cadherin could be conductive to nerve regeneration and repair probably by promoting the proliferation and differentiation of NSCs. PMID- 25135727 TI - Predictors of catheter-related bladder discomfort after urological surgery. AB - The aim of this study was to figure out the predictors of early postoperative catheter-related bladder discomfort (CRBD) after urological surgery. We designed a prospective observational study in our hospital. Consecutive adult patients undergoing surgery under general anaesthesia or epidural anaesthesia necessitating urinary catheterization were included during a 3-month period. severity of bladder discomfort was assessed on a 4-point scale: (1) no pain, (2) mild pain (revealed only by interviewing the patient), (3) moderate (a spontaneous complaint by the patient of a burning sensation in the urethra and/or an urge to urinate and/or sensation of urethral foreign body without any emotional agitation) and (4) severe discomfort (agitation, loud complaints and attempt to remove the bladder catheter associated with a burning sensation in the urethra). Predictors of CRBD were identified by univariate and multivariate analysis. Totally, 116 patients were included, of which 84.5% had CRBD (mild CRBD: 40.5%; moderate or severe CRBD: 44.0%) at day 1, while 31.9% developed CRBD (mild CRBD: 29.3%; moderate or severe CRBD: 2.6%) at day 3. We evaluated 9 potential forecast factors of CRBD, and univariate Chi-square test showed male gender [OR=2.4, 95%CI (1.1-5.6), P<0.05], abdominal open surgery compared with transurethral surgery [OR=0.3, 95%CI (0.1-0.6), P<0.05], abdominal surgery compared with laparoscopic surgery [OR=3.3, 95%CI (1.2-8.9), P<0.05] and history of catheterization [OR=0.5, 95%CI (0.2-0.9), P<0.05] were independent predictors of moderate or severe CRBD in the patients after surgery. While multivariate logistic regression analysis showed that the abdominal open surgery [EXP(B)=3.074, 95%CI (1.3-7.4), P<0.05] and the history of catheterization [EXP(B)=2.458, 95%CI (1.1-5.9), P<0.05] might contribute more to the occurrence of moderate or severe CRBD. In conclusion, this observational study identified that the type of surgery and the history of catheterization might be predictive factors of moderate and severe CRBD after urological surgery. PMID- 25135728 TI - A prospective randomized trial of selective versus nonselective esophagogastric devascularization for portal hypertension. AB - Cirrhosis with portal hypertension is a common disease which has a significant impact on the quality of patients' life. Esophagogastric devascularization (EGDV) has been demonstrated to be an effective method to treat portal hypertension, however certain complications are associated with it. The purpose of this study was to evaluate the effectiveness and clinical outcome of the selective EGDV (sEGDV) for the treatment of portal hypertension. The study was conducted prospectively from Jan. 1 2011 to Dec. 31, 2012, and 180 patients were randomized to the sEGDV group (n=90) or the non-sEGDV (n-sEGDV) group (n=90). Patients' demographics, preoperative lab test results and operative details were comparable between the two groups. Postoperative and short-term complications were analyzed in two groups. There was statistically significant difference (P<0.01) in the PVF reduction between the two groups. Post-operative complications showed no statistically significant difference between the two groups in the incidence of bleeding, ascites, acute portal vein thrombosis, fever and hepatic encephalopathy. Mortality between two groups was comparable. The incidence of splenic fossa effusion after the surgery was lower in sEGDV group than in n-sEGDV group. There were no significant differences in the short-term follow-up data such as esophageal varices and portal hypertensive gastropathy (P>0.05). It is suggested that sEGDV is a safe, simple and effective surgical procedure. It has both the advantages of the shunt and devascularization because it preserves body's voluntary diversion. With the advantage of low incidence of postoperative complications, it is an ideal surgical approach for the treatment of portal hypertension. PMID- 25135729 TI - Effect of electro-acupuncture stimulation of Ximen (PC4) and Neiguan (PC6) on remifentanil-induced breakthrough pain following thoracal esophagectomy. AB - The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 MUg, followed by a continuous infusion of 2.25 MUg/h. The patient self-administration of sufentanil was 0.75 MUg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma beta-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P<0.05). The total dose of sufentanil was 115+/-6.0 MUg in EAS group, significantly lower than that in control (134.3+/-5.9 MUg) and sham (133.5+/-7.0 MUg) groups. Similarly, the rescue dose of dezocine was the least in EAS group (P<0.05) among the three groups. Plasma beta-EP levels in EAS group at T3 (176.90+/-45.73) and T4 (162.96+/-35.00 pg/mL) were significantly higher than those in control (132.33+/ 36.75 and 128.79+/-41.24 pg/mL) and sham (136.56+/-45.80 and 129.85+/-36.14 pg/mL) groups, P<0.05 for all. EAS could decrease the release of PGE2. Plasma PGE2 levels in EAS group at T2 and T3 (41+/-5 and 40+/-5 pg/mL respectively) were significantly lower than those in control (64+/-5 and 62+/-7 pg/mL) and sham (66+/-6 and 62+/-6 pg/mL) groups. Plasma 5-HT levels in EAS group at T2 (133.66+/ 40.85) and T3 (154.66+/-52.49 ng/mL) were significantly lower than those in control (168.33+/-56.94 and 225.28+/-82.03) and sham (164.54+/-47.53 and 217.74+/ 76.45 ng/mL) groups. For intra-group comparison, plasma 5-HT and PGE2 levels in control and sham groups at T2 and T3, and beta-EP in EAS group at T3 and T4 were significantly higher than those at T1 (P<0.05); PGE2 and 5-HT levels in EAS group showed no significant difference among the different time points (P>0.05). No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous beta-EP and inhibition of inflammatory mediators (5-HT and PGE2). PMID- 25135731 TI - Analysis of clinical features of painless aortic dissection. AB - The clinical characteristics of painless aortic dissection were investigated in order to improve the awareness of diagnosis and treatment of atypical aortic dissection. The 482 cases of aortic dissection were divided into painless group and pain group, and the data of the two groups were retrospectively analyzed. The major clinical symptom was pain in 447 cases (92.74%), while 35 patients (7.26%) had no typical pain. The gender, age, hypertension, hyperlipidemia, diabetes, smoking and drinking history had no statistically significant differences between the two groups (P>0.05). The proportion of Stanford type A in painless group was significantly higher than that in pain group (48.57% vs. 21.03%, P=0.006). The incidence of unconsciousness in the painless group was significantly higher than that in the pain group (14.29% vs. 3.58%, P=0.011). The incidence of hypotension in painless group was significantly higher than that in pain group for 4.26 folds (P=0.01). Computed tomography angiography (CTA) examination revealed that the incidence of aortic arch involved in the painless group was significantly higher than that in the pain group (19.23% vs. 5.52%, P=0.019). It was concluded that the incidence of painless aortic dissection was higher in Stanford A type patients, commonly seen in the patients complicated with hypotension and unconsciousness. CTA examination revealed higher incidence of aortic arch involvement. PMID- 25135730 TI - Renovascular morphological changes in a rabbit model of hydronephrosis. AB - Obstructive nephropathy ultimately leads to end-stage renal failure. Renovascular lesions are involved in various nephropathies, and most renal diseases have an ischemic component that underlies the resulting renal fibrosis. The aim of this study was to investigate whether morphological changes occur in the renal vasculature in hydronephrosis and the possible mechanisms involved. A model of complete unilateral ureteral obstruction (CUUO) was used. Experimental animals were divided into five groups: a normal control group (N) and groups of animals at 1st week (O1), 2nd week (O2), 4th week (O4) and 8th week (O8) after CUUO. Blood pressure was measured, renal arterial trees and glomeruli were assessed quantitatively, and renovascular three-dimensional reconstruction was performed on all groups. Glomerular ultrastructural changes were examined by transmission electron microscopy. The results showed that the systolic blood pressure was significantly increased in the obstructed groups (O1, O2, O4 and O8). Three dimensional reconstruction showed sparse arterial trees in the O8 group, and a tortuous and sometimes ruptured glomerular basement membrane was found in the O4 and O8 groups. Furthermore, epithelial media thickness and media/lumen ratio were increased, lumen diameters were decreased, and the cross-sectional area of the media was unaltered in the segmental renal artery, interlobar artery and afferent arterioles, respectively. In conclusion, renal arterial trees and glomeruli were dramatically altered following CUUO and the changes may be partially ascribed to vascular remodeling. Elucidation of the molecular mechanisms of renovascular morphological alterations will enable the development of potential therapeutic approaches for hydronephrosis. PMID- 25135732 TI - Up-regulated expression of Tim-3/Gal-9 at maternal-fetal interface in pregnant woman with recurrent spontaneous abortion. AB - The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA. PMID- 25135733 TI - Effects of IL-17 on expression of GRO-alpha and IL-8 in fibroblasts from nasal polyps. AB - Recent studies indicated that interleukin (IL)-17, growth-related oncogene (GRO) alpha and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO alpha and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-alpha and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GRO-alpha and IL-8. The mRNA of GRO-alpha and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-alpha and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-alpha and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps. PMID- 25135734 TI - Analysis of Th1/Th2 response pattern for erythrodermic psoriasis. AB - As one of the most serious types of psoriasis, pathogenesis of erythrodermic psoriasis (EP) is unclear so far. In this study, we aimed to detect the levels of Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in peripheral blood mononuclear cells (PBMCs) derived from EP patients, and gene expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2 reaction pattern played in the pathogenesis of EP was also discussed. Serum levels of IFN-gamma, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP patients, 20 psoriasis vulgaris (PV) patients and 15 healthy controls. The expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels of IFN-gamma, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy controls. The levels of IL-4 and IL-10 were 69.44+/-11.45 and 12.62+/-4.57 pg/mL, respectively, in EP patients, significantly higher than those in PV patients and healthy controls (P<0.05). Flow cytometry revealed the levels of both Th1 and Th2 in PBMCs from EP patients were higher than those in healthy controls, and the Th1/Th2 ratio was dramatically lower than in PV patients (P<0.01). The ratios of IFN-gamma/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0, suggesting a reversal when compared with the other two groups. Our study indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern, and the balance of Th cell subsets inclines to Th2, which might be one of the important mechanisms of EP pathogenesis. PMID- 25135735 TI - Mutual effect between neuropeptides and inflammatory cytokines in neurogenic SMSCs of human temporomandibular joint. AB - In temporomandibular disorders (TMD), pain takes place when neuropeptides stimulate synovial tissue to produce several cytokines such as interleukin (IL) 1beta, IL-6 and tumor necrosis factor (TNF)-alpha, which activate neurons and glia of synovial membrane at the bilaminar regions of temporomandibular joint (TMJ). It has been reported that, after neurogenic differentiation, the synovial mesenchymal stem cells (SMSCs), deriving from TMJ, possess the same cytological features as the neuronal cells. This study examined the ability of substance P (SP) and calcitonin gene-related peptide (CGRP) to stimulate SMSCs and neurogenic SMSCs secreting inflammatory cytokines during TMD, evaluated the mutual effects of inflammatory cytokines and neuropeptides and tested the analgesic effect of hyaluronic acid (HA). The levels of IL-1beta, IL-6 and TNF-alpha in SMSCs and neurogenic SMSCs in the presence of neuropeptides were measured by ELISA. SP and CGRP produced by SMSCs and neurogenic SMSCs were determined by RT-PCR and Western blotting. The results showed that the expression of SP and CGRP was significantly enhanced in the neurogenic SMSCs in response to IL-1beta, IL-6 and TNF-alpha, and the effect was remarkably inhibited by HA. IL-1beta, IL-6 and TNF-alpha, in return, could be enhanced in the neurogenic SMSCs upon stimulation by SP and CGRP. Neuropeptides and inflammatory cytokines might work mutually on the TMD pain. The HA-mediated analgesic effect may be implicated in the inhibition of SP and CGRP expression in neurogenic SMSCs. PMID- 25135736 TI - Calcium hydroxide removal in curved root canals with apical transportation In Vitro. AB - Calcium hydroxide (CH) is applied to improve disinfection of root canals in most root canal retreatment. This study aimed to analyze the CH removal efficacy using 7 different root preparing files (K file, pre-curved K file, EndoActivator, Ultrasonic file, pre-curved ultrasonic file, F file and needle irrigation alone) with apical transportation. Standardized models of curved canal with such apical transportation or not were set up before applying CH to root canal for 7 days. Seven techniques described above were used for its removal. Then the roots were disassembled and digital photos were taken. The ratio of residual CH in the overall canal surface was calculated using the image analyzer image pro plus 6.0. The data were analyzed using one-way ANOVA with post hoc Tukey test. Results revealed that CH was effectively removed (P<0.05) by using all 6 mechanical methods except irrigation alone. In curved root canals with apical transportation, EndoActivator, pre-curved ultrasonic file and F file were found to be more effective in removing CH than the other four file (P<0.001), while there was no significant difference among EndoActivator, pre-curved ultrasonic file and F file groups (P>0.05). The percentage of residual CH in the canal with apical transportation was higher than that in the canal without apical transportation (P<0.05). In conclusion, CH can be hardly removed completely. Canal with apical transportation will result in insufficient CH removal. EndoActivator, pre-curved ultrasonic file and F file are more effective in the curved root canal with apical transportation. PMID- 25135737 TI - Safety and efficacy of endoscopic retrograde cholangiopancreatography for common bile duct stones in liver cirrhotic patients. AB - In order to investigate the safety and efficacy of endoscopic retrograde cholangiopancreatograpy (ERCP) in liver cirrhosis patients with common bile duct stones, we retrospectively analyzed data of 46 common bile duct stones patients with liver cirrhosis who underwent ERCP between 2000 and 2008. There were 12 cases of Child-Pugh A, 26 cases of Child-Pugh B, and 8 cases of Child-Pugh C. 100 common bile duct stones patients without liver cirrhosis were randomly selected. All the patients were subjected to ERCP for biliary stones extraction. The rates of bile duct clearance and complications were compared between cirrhotic and non cirrhotic patients. The success rate of selective biliary cannulation was 95.6% in liver cirrhotic patients versus 97% in non-cirrhotic patients (P>0.05). The bile duct clearance rate was 87% in cirrhotic patients versus 96% in non cirrhotic patients, but the difference was not statistically significant. Two liver cirrhotic patients (4.35%, 2/46) who were scored Child-Pugh C had hematemesis and melena 24 h after ERCP. The hemorrhage rate after ERCP in non cirrhotic patients was 3%. The hemorrhage rate associated with ERCP in Child-Pugh C patients was significantly higher (25%, 2/8) than that (3%, 3/100) in non cirrhotic patients (P<0.01%). There was no significant difference between these two groups in the rate of post-ERCP pancreatitis (PEP) and cholangitis. ERCP is safe and effective for Child-Pugh A and B cirrhotic patients with common bile duct stones. Hemorrhage risk in ERCP is higher in Child-Pugh C patients. PMID- 25135738 TI - Correlation between low tube voltage in dual source CT coronary artery imaging with image quality and radiation dose. AB - The influence of low tube voltage in dual source CT (DSCT) coronary artery imaging on image quality and radiation dose and its application value in clinical practice were investigated. Totally, 300 cases of chest pain with low body mass index (BMI <18.5 kg/m(2)) subjected to DSCT coronary artery imaging were prospectively enrolled. The heart rate in all patients were greater than 65/min. The retrospective ECG gated scanning mode and simple random sampling method were used to assign the patients into groups A, B and C (n=100 each). The patients in groups A, B and C experienced 120-, 100-, and 80-kV tube voltage imaging respectively, and the image quality was evaluated. The CT volume dose index (CTDIvol) and dose length product (DLP) were recorded, and the effective dose (ED) was calculated in each group. The image quality scores and radiation doses in groups were compared, and the influence of tube voltage on image quality and radiation dose was analyzed. The results showed that the excellent rate of image quality in groups A, B and C was 95.69%, 94.72% and 96.33% respectively with the difference being not statistically significant among the three groups (P>0.05). The CTDIvol values in groups A, B and C were 51.35+/-12.21, 21.28+/-7.13 and 6.34+/-3.34 mGy, respectively, with the difference being statistically significant (P<0.05). The ED values in groups A, B and C were 9.27+/-1.63, 4.56+/ 2.29 and 2.29+/-1.69 mSv, respectively, with the difference being statistically significant (P<0.05). It was suggested that for the patients with low BMI, the application of DSCT coronary artery imaging with low tube voltage can obtain satisfactory image quality, and simultaneously, significantly reduce the radiation dose. PMID- 25135739 TI - Electronically transparent graphene replicas of diatoms: a new technique for the investigation of frustule morphology. AB - The morphogenesis of the silica cell walls (called frustules) of unicellular algae known as diatoms is one of the most intriguing mysteries of the diatoms. To study frustule morphogenesis, optical, electron and atomic force microscopy has been extensively used to reveal the frustule morphology. However, since silica frustules are opaque, past observations were limited to outer and fracture surfaces, restricting observations of interior structures. Here we show that opaque silica frustules can be converted into electronically transparent graphene replicas, fabricated using chemical vapor deposition of methane. Chemical vapor deposition creates a continuous graphene coating preserving the frustule's shape and fine, complicated internal features. Subsequent dissolution of the silica with hydrofluoric acid yields a free-standing replica of the internal and external native frustule morphologies. Electron microscopy renders these graphene replicas highly transparent, revealing previously unobserved, complex, three dimensional, interior frustule structures, which lend new insights into the investigation of frustule morphogenesis. PMID- 25135740 TI - LDH is an adverse prognostic factor independent of ISS in transplant-eligible myeloma patients receiving bortezomib-based induction regimens. AB - BACKGROUND: Serum lactate dehydrogenase (LDH) has been an adverse prognostic factor for myeloma but does not feature in the International Staging System (ISS). We examined whether elevated serum LDH at diagnosis remains an adverse risk factor independent of ISS for survivals transplant-eligible myeloma patients receiving early/frontline bortezomib-based induction, followed by autologous stem cell transplantation (ASCT). PATIENTS: Seventy-seven transplant-eligible Chinese patients received three induction regimens [staged approach (N = 25), PAD (N = 19), VTD (N = 33)], followed by ASCT and thalidomide maintenance. RESULTS: Five year overall (OS) and event-free (EFS) survivals were 66.4% and 36.2%. There was no difference in demographics, complete remission/near complete remission (CR/nCR rates postinduction or ASCT, and survivals among patients induced by the three induction regimens. Elevated LDH was associated with male gender (P = 0.006), ISS III (P = 0.042) and serum beta2-microglobulin (P = 0.040). Univariate analysis showed that elevated LDH, ISS III, high beta2-microglobulin, and failure to attain CR/nCR post-ACST were risk factors adversely impacting both OS and EFS. Multivariate analysis showed that elevated LDH was the only factor impacting both OS (P = 0.007) and EFS (P = 0.008). CONCLUSION: In this uniformly treated cohort of transplant-eligible myeloma patients, elevated serum LDH is an adverse risk factor independent of ISS for both OS and EFS. Bortezomib-based induction/ASCT regimen had not abolished the adverse impact of elevated LDH. PMID- 25135741 TI - Silica exposure and altered regulation of autoimmunity. AB - Silica particles and asbestos fibers, which are known as typical causatives of pneumoconiosis, induce lung fibrosis. Moreover, silicosis patients often complicate with autoimmune diseases, and asbestos-exposed patients suffer from malignant diseases such as pleural mesothelioma and lung cancer. We have been conducting experimental studies to investigate altered regulation of self tolerance caused by silica exposure, including analyses using specimens such as plasma and immunocompetent cells obtained from silicosis patients, as a means of examining the supposition that silica exposure induces molecular and cellular biological alterations of immune cells. These approaches have resulted in the detection of several specific autoantibodies, alterations of CD95/Fas and its related molecules, and evidence of chronic activation of responder T cells and regulatory T cells following silica exposure. In this review, we present details of our investigations as an introduction to scientific approaches examining the immunological effects of environmental and occupational substances. PMID- 25135742 TI - Reduced dynamic hyperinflation after LVRS is associated with improved exercise tolerance. AB - INTRODUCTION: Dynamic hyperinflation (DH) after lung volume reduction surgery (LVRS) has not been well studied. It is not known if reductions in DH correlate with improvements in exercise performance post-LVRS. METHODS: Forty-two upper lobe predominant emphysema patients who underwent LVRS were analyzed. Inspiratory capacity was measured every 2 min during symptom-limited cardiopulmonary exercise test (CPET) and end-expiratory lung volumes (EELV) were calculated. The main measure of DH was EELV/TLC ratio matched at metabolic isotimes (based on the post rehabilitation VCO2max). RESULTS: Patients had very severe airflow obstruction (FEV1 28.3 +/- 7.0% predicted), were hyperinflated (TLC 125 +/- 17% predicted) and gas trapped (RV 198 +/- 39% predicted). Compared to the post-rehab baseline, dynamic hyperinflation (EELV/TLC) was significantly reduced after LVRS at 6, 12, 24, and 36 months. There were also increases in inspiratory reserve volume at matched isotimes after surgery. Patients adopted a slower, deeper breathing pattern during exercise after LVRS, which strongly correlated to reductions in DH. There were significant correlations between reductions in DH (EELV/TLC @50% VCO2max) and improvements in 6 min walk distance (Pearson r = -0.411, p = 0.02, n = 33) and maximal watts on CPET (Spearman r = -0.536, p = 0.001, n = 33) when comparing post-rehabilitation and 6 month post-LVRS values. CONCLUSION: Dynamic hyperinflation during exercise was reduced after LVRS (up to 3 years) and there was a strong association between alterations in breathing pattern and reduced DH after LVRS. This is the first study to demonstrate that reductions in DH correlated with improved exercise performance following LVRS. PMID- 25135743 TI - Pooled safety analysis of the fixed-dose combination of indacaterol and glycopyrronium (QVA149), its monocomponents, and tiotropium versus placebo in COPD patients. AB - BACKGROUND: To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium (QVA149) and its monocomponents; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme with relevant information from the independent indacaterol and glycopyrronium safety databases. METHODS: Data from 11,404 patients with chronic obstructive pulmonary disease (COPD) were pooled from 14 clinical studies of QVA149, indacaterol and glycopyrronium of >=3 month's duration with at least two of the treatment groups: QVA149 110/50 MUg, glycopyrronium 50 MUg, indacaterol 150 MUg, placebo or tiotropium 18 MUg. Overall hazard ratio (HR) was assessed between the active treatments and placebo and in various subgroups related to severity of airways obstruction, inhaled corticosteroid use, cardiovascular risk factors, sex, age and body mass index for death, serious cases of cardio- and cerebrovascular (CCV) events, major adverse cardiovascular events (MACEs), pneumonia, COPD exacerbations requiring hospitalisation or atrial flutter/fibrillation (AF/F). RESULTS: The HR for QVA149 versus placebo showed no significant increase in the overall risk for death (HR [95% confidence interval]: 0.93 [0.34-2.54]); CCV events (0.60 [0.29-1.24]); MACE (1.04 [0.45-2.42]); pneumonia (1.10 [0.54-2.25]); COPD exacerbations (0.60 [0.40-0.91]); and AF/F (1.03 [0.49-2.18]). Similar results were observed for indacaterol, glycopyrronium and tiotropium versus placebo for overall risk and in analysed subgroups. CONCLUSIONS: There was no increase in the risk for the investigated safety endpoints for the fixed-dose combination QVA149, and it had a comparable safety profile as its monocomponents and tiotropium versus placebo. PMID- 25135744 TI - SQ HDM SLIT-tablet (ALK) in treatment of asthma--post hoc results from a randomised trial. AB - INTRODUCTION: In a double-blind, placebo-controlled trial (EudraCT identifier: 2006-001795-20), the standardised quality (SQ) house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet (ALK, Denmark) was investigated. METHOD: The trial included 604 subjects, >=14 years, with mild-moderate HDM allergic asthma. Subjects were randomised 1:1:1:1 to 1, 3 or 6 SQ-HDM or placebo once daily. The primary endpoint was reduction in inhaled corticosteroid (ICS) after one year. ICS reduction, asthma quality of life questionnaire (AQLQ) and asthma control questionnaire (ACQ) score was analysed post hoc in a subgroup with daily ICS use of 400-800 MUg and ACQ score of 1-1.5, corresponding to partly controlled asthma (N = 108). RESULTS: The trial met its primary endpoint. In the subgroup, the difference between placebo and 6 SQ-HDM in change from baseline in daily ICS use was 327 MUg (p < 0.0001), while it was 0.52 (p = 0.010) for AQLQ. The treatment effect on ICS reduction and AQLQ was increased for the subgroup versus the residual population (ICS reduction: p < 0.001); AQLQ: p = 0.044). CONCLUSION: In this subgroup, including only patients with partly controlled asthma, the benefit of 1 year of treatment with SQ HDM SLIT-tablet was significantly higher than for the less severe full population, both in terms of increased asthma control and improved quality of life. PMID- 25135745 TI - Persistent systemic inflammation and symptoms of depression among patients with COPD in the ECLIPSE cohort. AB - BACKGROUND: Depression is highly prevalent among patients with Chronic Obstructive Pulmonary Disease (COPD). The relationship of depression with systemic inflammation in COPD remains unknown. The objective of this observational study was to compare depression scores at baseline and after 36 months follow-up between COPD patients with persistent systemic inflammation (PSI) and never inflamed patients (NI) in the ECLIPSE cohort. METHODS: The ECLIPSE study included 2164 COPD patients. Parameters assessed at baseline and at 36 months follow-up included: demographics, clinical characteristics and symptoms of depression (Center for Epidemiologic Studies of Depression, CES-D). Patients classified as NI had zero and patients with PSI had >=2 inflammatory biomarkers (white blood cell count, hsCRP, IL-6, and fibrinogen) in the upper quartile, at baseline and 12 months later. FINDINGS: 350 patients (29.1%) were NI and 131 patients (10.9%) had PSI. At baseline, mean CES-D score was higher in patients with PSI than in NI patients (11.7 (8.6) vs. 9.2 (8.9) points, p = 0.01). Differences were not confirmed after adjustment for possible confounders (beta (95% CI) = 0.02 (-3.87 to 15.29), adjusted p = 0.98). At 36 months follow-up, CES D scores were comparable in PSI and NI patients (12.2 (9.3) vs. 10.5 (9.0) points, p = 0.08) as were their temporal changes (0.5 (8.3) vs. 1.3 (7.9) points, p = 0.30). CONCLUSION: The ECLIPSE study does not support a strong relationship between PSI and symptoms of depression at baseline and after 36 months follow-up in COPD. FUNDING: The study was sponsored by GlaxoSmithKline. PMID- 25135746 TI - Evaluation of epicardial fat tissue thickness in patients with hyperthyroidism. AB - BACKGROUND: Thyroid hormones have several effects on the cardiovascular system, and recent studies have found that thyroid disorders affect coronary intima-media thickness (CIMT) in particular. Despite increased CIMT in patients with hyperthyroidism, the extent of the relationship between CIMT and epicardial fat thickness (EFT) in those patients is unknown. Furthermore, there is no report evaluating the relationship between EFT and overt hyperthyroidism (OH) in the literature. In this study, we aim to evaluate the effectiveness of EFT in predicting atherosclerosis as well as CIMT in patients with OH. METHODS: A total of 30 newly diagnosed, untreated overt hyperthyroid patients and 44 control subjects were included in the study. EFT was measured using a commercially available echocardiography machine (VIVID 7; General Electric Medical Systems, Norway) with a 2.5-MHz probe. The echo-free space between the visceral and parietal pericardium on the anterior wall of the right ventricle was diagnosed as EFT. A linear-array imaging probe of the same echocardiography probe was used to evaluate the CIMT of the right common carotid artery. RESULTS: The hyperthyroid patients had a significantly greater EFT (mean: 4.31 +/- 1.12 mm) than the healthy subjects (mean: 3.11 +/- 0.84 mm; p < 0.001). CIMT was also significantly greater in the hyperthyroid patients (mean: 0.62 +/- 0.17 mm) than in the healthy subjects (mean: 0.50 +/- 0.11 mm; p < 0.01). CONCLUSION: In conclusion, the present study shows that mean EFT and CIMT were significantly higher in OH patients, irrespective of confounding factors such as hypertension. PMID- 25135747 TI - Differentiation of DctA and DcuS function in the DctA/DcuS sensor complex of Escherichia coli: function of DctA as an activity switch and of DcuS as the C4 dicarboxylate sensor. AB - The C4-dicarboxylate responsiveness of the sensor kinase DcuS is only provided in concert with C4-dicarboxylate transporters DctA or DcuB. The individual roles of DctA and DcuS for the function of the DctA/DcuS sensor complex were analysed. (i) Variant DctA(S380D) in the C4-dicarboxylate site of DctA conferred C4 dicarboxylate sensitivity to DcuS in the DctA/DcuS complex, but was deficient for transport and for growth on C4-dicarboxylates. Consequently transport activity of DctA is not required for its function in the sensor complex. (ii) Effectors like fumarate induced expression of DctA/DcuS-dependent reporter genes (dcuB-lacZ) and served as substrates of DctA, whereas citrate served only as an inducer of dcuB lacZ without affecting DctA function. (iii) Induction of dcuB-lacZ by fumarate required 33-fold higher concentrations than for transport by DctA (Km = 30 MUM), demonstrating the existence of different fumarate sites for both processes. (iv) In titration experiments with increasing dctA expression levels, the effect of DctA on the C4-dicarboxylate sensitivity of DcuS was concentration dependent. The data uniformly show that C4-dicarboxylate sensing by DctA/DcuS resides in DcuS, and that DctA serves as an activity switch. Shifting of DcuS from the constitutive ON to the C4-dicarboxylate responsive state, required presence of DctA but not transport by DctA. PMID- 25135748 TI - Synthesis of novel carbazole fused coumarin derivatives and DFT approach to study their photophysical properties. AB - Novel coumarin derivatives have been synthesized by the classical Knoevenagel condensation of 4-hydroxy-9-methyl-9H-carbazole-3-carbaldehyde with active methylene compounds and characterized. Effect of solvent polarity on the photophysical properties, absorption and emission has been studied. The photophysical properties of the synthesized coumarins have been compared with some of the established analogous coumarin derivatives. Investigation of the structural parameters and understanding photophysical properties of the synthesized coumarin derivatives were carried out using Density Functional Theory (DFT) and Time Dependant Density Functional Theory (TDDFT) computations. The experimental values were correlated with the theoretical derived results. The ratio of the excited state and the ground state dipole moments was calculated by using solvatochromic and solvatofluoric data and compared with the values obtained from DFT and TDDFT computations. PMID- 25135749 TI - Regarding the tongue protrusion as an indicator of vital burning. Much ado about nothing. PMID- 25135750 TI - Molecular analysis of different classes of RNA molecules from formalin-fixed paraffin-embedded autoptic tissues: a pilot study. AB - For a long time, it has been thought that fresh and frozen tissues are the only possible source of biological material useful to extract nucleic acids suitable for downstream molecular analysis. Recently, for forensic purpose such as personal identification, also fixed tissues have been used to recover DNA molecules, whereas RNA extracted from such material is still considered too degraded for gene expression studies. In the present pilot study, we evaluated the possibility to use forensic formalin-fixed paraffin-embedded (FFPE) samples, collected at autopsy at different postmortem intervals (PMI) from four individuals, to perform advanced molecular analyses. In particular, we performed qualitative and quantitative analyses of total RNAs extracted from different FFPE tissues and put expression profiles in relation with the organ type and the duration of PMI. Different classes of RNA molecular targets were studied by real time quantitative RT-PCR. We report molecular evidence that small RNAs are the only RNA molecules still detectable in all the FFPE autoptic tissues. In particular, microRNAs (miRNAs) represent a consistent, stable, and well-preserved molecular target detectable even from tissue sources displaying signs of ongoing putrefaction at autopsy. In this pilot study, we show that miRNAs could represent a highly sensitive and potentially useful forensic marker. Amplification of specific miRNAs using paraffin-embedded blocks could facilitate retrospective molecular analysis using specific forensic-archived tissues chosen as most suitable according to PMI, and this approach would address molecular evidence in forensic cases in which fresh or frozen material is no longer available. PMID- 25135751 TI - Projection radiography of the clavicle: still recommendable for forensic age diagnostics in living individuals? AB - As superimposition effects often impede the evaluation of the ossification status of the medial clavicular epiphysis in standard posterior-anterior (PA) radiographs, additional oblique images (right anterior oblique, RAO, and left anterior oblique, LAO) are currently recommended to allow for reliable stage assessments. The present study examines the influence of the radiographic projection type on stage determination. To this end, 836 sternoclavicular joints were prospectively obtained during forensic autopsies of bodies aged between 15 and 30 years. Subsequently, three different radiographs (PA, RAO, and LAO) were taken from each specimen and separately evaluated as to the developmental stage of the medial clavicular epiphysis. A forensically established five-stage classification system was used. In 25 % of the cases, the medial clavicular epiphysis depicted in an oblique projection showed a different ossification stage than in the PA projection. In at least 10 % of the cases, a higher ossification stage was observed which would have significant disadvantages in criminal proceedings (ethically unacceptable error). In conclusion, the usage of the current radiographic reference data, which rely upon chest radiographs taken as PA projections, appears to be inadmissible for oblique projections. Projection radiography of the clavicle can therefore no longer be recommended for forensic age estimation practice. As to the question of whether an individual has achieved the age of 18 or 21, computed tomography of the clavicle must be regarded as the exclusive method of choice. PMID- 25135752 TI - CD30 expression in de novo diffuse large B-cell lymphoma: a population-based study from British Columbia. AB - Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable therapeutic responses and alternative therapies are needed for patients with unfavourable treatment outcomes after standard treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). One promising candidate is brentuximab vedotin, an antibody-drug conjugate targeting CD30-expressing cells. However, CD30 (TNFRSF8) expression patterns in DLBCL are not well described thus far. Here, we examined CD30 expression in a population-based cohort of immunocompetent patients from British Columbia with de novo DLBCL using immunohistochemistry. 385 cases of formalin-fixed paraffin-embedded DLBCL in tissue microarrays were evaluated. 95 cases (25%) harboured CD30+ tumour cells. Using a > 0% cut-off, CD30 expression was predictive of superior 5-year progression-free survival within R-CHOP treated germinal centre B-cell-like (GCB) DLBCL (86% vs. 64%, P = 0.020), which was independent of the International Prognostic Index. Epstein-Barr virus (EBV) was identified in 11 (3%) cases, all of which were non-GCB (P = 0.001) and almost exclusively positive for CD30 expression (10/11) (P < 0.001). We conclude CD30 is expressed in a substantial proportion of DLBCL and CD30 immunohistochemistry may be a useful prognostic marker in R-CHOP treated GCB-DLBCL. The significant association of CD30 with EBV positive non-GCB DLBCL suggests a distinct pathobiology for these cases. PMID- 25135753 TI - Purifying selection against gene conversions between the polyamine transport (TPO) genes of Saccharomyces species. AB - Saccharomyces species have five TPO genes, TPO1 through TPO5, coding for proteins that are involved in up taking or excreting intracellular spermine, putrescine or spermidine. Here, we investigate the evolutionary fate and functional impacts of gene conversions between these genes. Our results show that gene conversions occurred only between the TPO2 and TPO3 genes of the six Saccharomyces species we studied. They also show that these gene conversions occurred independently in all six species. The facts that they only occur between closely related genes having similar function, and that they are limited to the transmembrane domain of these proteins, suggest that they have little functional impact. These gene conversions therefore likely represent neutral mutations which are not subject to purifying selection. PMID- 25135755 TI - Spin-orbit effects in square-planar Pt(II) complexes with bidentate and terdentate ligands: theoretical absorption/emission spectroscopy. AB - The absorption and emission properties of five Pt(ii) planar complexes with bidentate ligands, namely [Pt(bpy)Cl2] (bpy = 2,2'-bipyridine) and [Pt(ppy)Cl2]( ) (ppy = 2-phenylpyridine) , and terdentate ligands, namely [Pt(tpy)Cl](+) (tpy = 2,2':6',2''-terpyridine) , [Pt(phbpyR)Cl] (phbpy = 6-phenyl-2,2'-bipyridine; R = H) and [Pt(dpybR)Cl] (dpyb = 2,6-di(2-pyridyl)benzene; R = CH3) were investigated by means of density functional theory (DFT) and time-dependent DFT (TD-DFT) methods including solvent correction and spin-orbit coupling (SOC). The DFT optimized structures of the five complexes in the electronic ground state are in agreement with the experimental X-ray data and the theoretical absorption spectra reproduce quantitatively the main features of the experimental spectra. It is shown that the structures remain nearly planar in the low-lying singlet and triplet excited states of charge transfer character, metal-to-ligand (MLCT) or halide (Cl) to ligand (XLCT) whereas a significant distortion corresponding to the out-of-plane-bending of the Pt-Cl bond characterizes the geometry of the metal-centered (MC) states. In cyclometalated complexes , and this distortion is energetically unfavorable and not competitive with radiative decay via the low lying MLCT and XLCT excited states. The absorption spectra of all complexes are significantly affected by spin-orbit coupling (red-shift and broadening), especially in the non-cyclometalated complexes and characterized by the presence of pure low-lying (3)MC states. The SOC effects are less important in the terpyridine complex the lowest part of its spectrum being contaminated by mixed (3)MLCT/(3)XLCT states. In the cyclometalated complexes and the presence of several LC states in the lowest part of the spectra is responsible for a small shift to the red as compared to the other complexes. The solvatochromism that characterizes the absorption of this class of molecules in the visible region is interpreted by the MLCT/XLCT mixed character of the excited states in this energy domain (400-450 nm). Indeed the solvent dependent XLCT contribution will control the magnitude of SOC in these excited states and will move the band to the red region when diminishing and to the blue region when increasing. As far as emission is concerned it is shown that strongly distorted non-radiative MC state's minima, situated below the charge transfer state's minima (DeltaE = -0.3 eV to -0.8 eV) are easily accessible upon irradiation in the visible region in complexes and , and in to a lesser extent, leading to no or low luminescence at room temperature. In contrast, the minima of the emissive states of mixed MLCT/XLCT/LC character are efficiently populated in and . The luminescence of complex , cyclometalated in the axial position, is particularly efficient because the minimum of the lowest emissive state is well separated from those of the MC states (DeltaE = +0.23 eV) in contrast to its analog, complex , cyclometalated in the lateral position where the emissive MLCT/LC state minimum is nearly degenerate with the lowest MC state minimum (DeltaE = +0.01 eV). PMID- 25135754 TI - Clinical utility and diagnostic accuracy of faecal calprotectin for IBD at first presentation to gastroenterology services in adults aged 16-50 years. AB - BACKGROUND: Distinguishing inflammatory bowel disease (IBD) from functional gastrointestinal (GI) disease remains an important issue for gastroenterologists and primary care physicians, and may be difficult on the basis of symptoms alone. Faecal calprotectin (FC) is a surrogate marker for intestinal inflammation but not cancer. AIM: This large retrospective study aimed to determine the most effective use of FC in patients aged 16-50 presenting with GI symptoms. METHODS: FC results were obtained for patients presenting to the GI clinics in Edinburgh between 2005 and 2009 from the Edinburgh Faecal Calprotectin Registry containing FCs from >16,000 patients. Case notes were interrogated to identify demographics, subsequent investigations and diagnoses. RESULTS: 895 patients were included in the main analysis, 65% female and with a median age of 33 years. 10.2% were diagnosed with IBD, 7.3% with another GI condition associated with an abnormal GI tract and 63.2% had functional GI disease. Median FC in these three groups were 1251, 50 and 20 MUg/g (p < 0.0001). On ROC analysis, the AUC for FC as a predictor of IBD vs. functional disease was 0.97. Using a threshold of >= 50 MUg/g for IBD vs. functional disease yielded a sensitivity of 0.97, specificity of 0.74, positive predictive value of 0.37 and negative predictive value of 0.99. Combined with alarm symptoms, the sensitivity was 1.00. CONCLUSIONS: Implementation of FC in the initial diagnostic workup of young patients with GI symptoms, particularly those without alarm symptoms, is highly accurate in the exclusion of IBD, and can provide reassurance to patients and physicians. PMID- 25135756 TI - Late pulmonary complications of treating Hodgkin lymphoma: bleomycin-induced toxicity. AB - INTRODUCTION: Survival of Hodgkin lymphoma (HL) patients has significantly improved in recent decades. The current first-line therapy is doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) +/- irradiation and may cause pulmonary toxicity. Strategies to reduce late toxicity as well as increase survival rate are of interest. PATIENTS AND METHODS: Pulmonary function of previously treated HL patients was collected over a 12-month period using St. George Respiratory Questionnaire (SGRQ), chest X-ray, dynamic inhalation lung scintigraphy and spirometry. RESULTS: A total of 137 patients' data were reviewed. Median time elapsed since diagnosis was 11 years (range was 2 - 30 years). Chest irradiation did not significantly worsen pulmonary function. Number of ABVD cycles with consequential bleomycin dose showed significant correlation with SGRQ total score in patients receiving ABVD plus chest irradiation (p = 0.01). Scintigraphy results correlated with bleomycin dose in patients receiving ABVD without chest irradiation (right side: p = 0.099, left side: p = 0.051). DISCUSSION: An additive negative effect of chest irradiation was not confirmed as reflected in the literature; however, increasing cumulative bleomycin dose worsened pulmonary function. PMID- 25135757 TI - A neighboring group participation strategy: direct and highly diastereoselective synthesis of 2-substituted and 2,2-bisubstituted perhydrofuro[2,3-b]pyran derivatives. AB - Treatment of methyl 2-C-formylmethyl-2-deoxy-beta-D-glucopyranoside (5) or methyl 2-C-acetylmethyl-2-deoxy-beta-D-glucopyranoside (1) with H2SO4-HOAc-Ac2O gave 2 acetoxyl-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]hexahydrofuro[2,3-b]pyran (6) and acetyl 2-C-acetylmethyl-2-deoxy-alpha-D-glucopyranoside (7) respectively, which were further reacted with nucleophiles in the presence of TMSOTf and offered a series of 2-substituted and 2,2-disubstituted perhydrofuro[2,3-b]pyran derivatives in high yield with excellent diastereoselectivity. PMID- 25135758 TI - Automated hematologic analysis of bone marrow aspirate samples from healthy Beagle dogs. AB - BACKGROUND: Interpretation of bone marrow (BM) smears typically is comprised of qualitative assessment and differential counting of cells. Analysis of BM fluid with automated hematology analyzers may provide rapid characterization of cells to supplement microscopic interpretation. OBJECTIVES: The purpose of the study was to examine the practicality and utility of analyzing BM samples in the Advia 2120 hematology analyzer; to determine if results correlate with smear assessment; and to establish descriptive statistics from hematologically normal and clinically healthy Beagle dogs. METHODS: Anticoagulated BM aspirates from 3 different sites of 26 adult Beagle dogs were collected. BM samples were analyzed in the Advia 2120, and numerical results were correlated with microscopic assessment of corresponding BM smears. Results from automated analyses and manual 500-cell differential counts were statistically analyzed. RESULTS: Forty-six samples were suitable for complete analysis. Results were available in approximately 2 (Advia) and 30 (stained and cover-slipped smear) minutes. Advia nucleated cell concentration was significantly correlated with microscopic assessment of smear particle number and smear cellularity. Significant correlations were also identified for Advia percent neutrophils with segmented, band and metamylocyte neutrophils, Advia percent lymphocytes with rubricytes, and Advia percent large unstained cells (LUC) with myeloblasts and promyelocytes. CONCLUSIONS: Automated analysis of BM aspirates was practicable, although techniques to obtain cellular samples and avoid clot formation could be improved. Automated analysis may provide rapid and useful preliminary information regarding sample cellularity, and granulocytic and erythrocytic components. Automated analysis should not supplant microscopic assessment, but may be a useful adjunct. PMID- 25135761 TI - Nonlinear emission of quinolizinium-based dyes with application in fluorescence lifetime imaging. AB - Charged molecules based on the quinolizinum cation have potential applications as labels in fluorescence imaging in biological media under nonlinear excitation. A systematic study of the linear and nonlinear photophysics of derivatives of the quinolizinum cation substituted by either dimethylaniline or methoxyphenyl electron donors is performed. The effects of donor strength, conjugation length, and symmetry in the two-photon emission efficiency are analyzed in detail. The best performing nonlinear fluorophore, with two-photon absorption cross sections of 1140 GM and an emission quantum yield of 0.22, is characterized by a symmetric D-pi-A(+)-pi-D architecture based on the methoxyphenyl substituent. Application of this molecule as a fluorescent marker in optical microscopy of living cells revealed that, under favorable conditions, the fluorophore can be localized in the cytoplasmatic compartment of the cell, staining vesicular shape organelles. At higher dye concentrations and longer staining times, the fluorophore can also penetrate into the nucleus. The nonlinearly excited fluorescence lifetime imaging shows that the fluorophore lifetime is sensitive to its location in the different cell compartments. Using fluorescence lifetime microscopy, a multicolor map of the cell is drafted with a single dye. PMID- 25135759 TI - Temporal spying and concealing process in fibre-optic data transmission systems through polarization bypass. AB - Recent research has been focused on the ability to manipulate a light beam in such a way to hide, namely to cloak, an event over a finite time or localization in space. The main idea is to create a hole or a gap in the spatial or time domain so as to allow for an object or data to be kept hidden for a while and then to be restored. By enlarging the field of applications of this concept to telecommunications, researchers have recently reported the possibility to hide transmitted data in an optical fibre. Here we report the first experimental demonstration of perpetual temporal spying and blinding process of optical data in fibre-optic transmission line based on polarization bypass. We successfully characterize the performance of our system by alternatively copying and then concealing 100% of a 10-Gb s(-1) transmitted signal. PMID- 25135760 TI - Smoking induces overexpression of immediate early genes in active Graves' ophthalmopathy. AB - BACKGROUND: Cigarette smoking is a risk factor for the development of Graves' ophthalmopathy (GO). In a previous study of gene expression in intraorbital fat, adipocyte-related immediate early genes (IEGs) were overexpressed in patients with GO compared to controls. We investigated whether IEGs are upregulated by smoking, and examined other pathways that may be affected by smoking. METHODS: Gene expression in intraorbital fat was studied in smokers (n=8) and nonsmokers (n=8) with severe active GO, as well as in subcutaneous fat in thyroid-healthy smokers (n=5) and nonsmokers (n=5) using microarray and real-time polymerase chain reaction (PCR). RESULTS: With microarray, eight IEGs were upregulated more than 1.5-fold in smokers compared to nonsmokers with GO. Five were chosen for confirmation and were also overexpressed with real-time PCR. Interleukin-1 beta/IL-1B/(2.3-fold) and interleukin-6/IL-6/(2.4-fold) were upregulated both with microarray and with real-time PCR in smokers with GO compared to nonsmokers. Major histocompatibility complex, class II, DR beta 1/HLA-DRB1/was upregulated with microarray (2.1-fold) and with borderline significance with real-time PCR. None of these genes were upregulated in smokers compared to nonsmokers in subcutaneous fat. CONCLUSIONS: IEGs, IL-1B, and IL-6 were overexpressed in smokers with severe active GO compared to nonsmokers, suggesting that smoking activates pathways associated with adipogenesis and inflammation. This study underlines the importance of IEGs in the pathogenesis of GO, and provides evidence for possible novel therapeutic interventions in GO. The mechanisms activated by smoking may be shared with other conditions such as rheumatoid arthritis. PMID- 25135762 TI - Complement mutations in diacylglycerol kinase-epsilon-associated atypical hemolytic uremic syndrome. AB - BACKGROUND AND OBJECTIVES: Atypical hemolytic uremic syndrome is characterized by vascular endothelial damage caused by complement dysregulation. Consistently, complement inhibition therapies are highly effective in most patients with atypical hemolytic uremic syndrome. Recently, it was shown that a significant percentage of patients with early-onset atypical hemolytic uremic syndrome carry mutations in diacylglycerol kinase-epsilon, an intracellular protein with no obvious role in complement. These data support an alternative, complement independent mechanism leading to thrombotic microangiopathy that has implications for treatment of early-onset atypical hemolytic uremic syndrome. To get additional insights into this new form of atypical hemolytic uremic syndrome, the diacylglycerol kinase-epsilon gene in a cohort with atypical hemolytic uremic syndrome was analyzed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eighty three patients with early-onset atypical hemolytic uremic syndrome (<2 years) enrolled in the Spanish atypical hemolytic uremic syndrome registry between 1999 and 2013 were screened for mutations in diacylglycerol kinase-epsilon. These patients were also fully characterized for mutations in the genes encoding factor H, membrane cofactor protein, factor I, C3, factor B, and thrombomodulin CFHRs copy number variations and rearrangements, and antifactor H antibodies. RESULTS: Four patients carried mutations in diacylglycerol kinase-epsilon, one p.H536Qfs*16 homozygote and three compound heterozygotes (p.W322*/p.P498R, two patients; p.Q248H/p.G484Gfs*10, one patient). Three patients also carried heterozygous mutations in thrombomodulin or C3. Extensive plasma infusions controlled atypical hemolytic uremic syndrome recurrences and prevented renal failure in the two patients with diacylglycerol kinase-epsilon and thrombomodulin mutations. A positive response to plasma infusions and complement inhibition treatment was also observed in the patient with concurrent diacylglycerol kinase epsilon and C3 mutations. CONCLUSIONS: Data suggest that complement dysregulation influences the onset and disease severity in carriers of diacylglycerol kinase epsilon mutations and that treatments on the basis of plasma infusions and complement inhibition are potentially useful in patients with combined diacylglycerol kinase-epsilon and complement mutations. A comprehensive understanding of the genetic component predisposing to atypical hemolytic uremic syndrome is, therefore, critical to guide an effective treatment. PMID- 25135763 TI - Factors influencing treatment of atypical hemolytic uremic syndrome. PMID- 25135764 TI - Implementation of a CKD checklist for primary care providers. AB - BACKGROUND AND OBJECTIVES: CKD is associated with significant morbidity, mortality, and financial burden. Practice guidelines outlining CKD management exist, but there is limited application of these guidelines. Interventions to improve CKD guideline adherence have been limited. This study evaluated a new CKD checklist (a tool outlining management guidelines for CKD) to determine whether implementation in an academic primary care clinic improved adherence to guidelines. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: During a 1-year period (August 2012-August 2013), a prospective study was conducted among 13 primary care providers (PCPs), four of whom were assigned to use a CKD checklist incorporated into the electronic medical record during visits with patients with CKD stages 1-4. All providers received education regarding CKD guidelines. The intervention and control groups consisted of 105 and 263 patients, respectively. Adherence to CKD management guidelines was measured. RESULTS: A random-effects logistic regression analysis was performed to account for intra-group correlation by PCP assignment and adjusted for age and CKD stage. CKD care improved among patients whose PCPs were assigned to the checklist intervention compared with controls. Patients in the CKD checklist group were more likely than controls to have appropriate annual laboratory testing for albuminuria (odds ratio [OR], 7.9; 95% confidence interval [95% CI], 3.6 to 17.2), phosphate (OR, 3.5; 95% CI, 1.5 to 8.3), and parathyroid hormone (OR, 8.1; 95% CI, 4.8 to 13.7) (P<0.001 in all cases). Patients in the CKD checklist group had higher rates of achieving a hemoglobin A1c target<7% (OR, 2.7; 95% CI, 1.4 to 5.1), use of an angiotensin converting enzyme inhibitor or angiotensin-receptor blocker (OR, 2.1; 95% CI, 1.0 to 4.2), documentation of avoidance of nonsteroidal anti-inflammatory drugs (OR, 41.7; 95% CI, 17.8 to 100.0), and vaccination for annual influenza (OR, 2.1; 95% CI, 1.1 to 4.0) and pneumococcus (OR, 4.7; 95% CI, 2.6 to 8.6) (P<0.001 in all cases). CONCLUSIONS: Implementation of a CKD checklist significantly improved adherence to CKD management guidelines and delivery of CKD care. PMID- 25135765 TI - Checklists as computer decision support at the point of care: a step forward in the recognition and treatment of CKD by primary care physicians. PMID- 25135767 TI - Commentary: Getting fathers into parenting programmes--a reflection on Panter Brick et al. (2014). AB - Research, policy and clinical practice focussed on engaging and working with fathers and their children often seems to oscillate between extremes. Where policy documents relating to children's health and wellbeing do include fathers it is often in a restricted way, and similarly discussions about the role of fathers in the media are often one-dimensional. It is sometimes hard to escape a feeling of despondency at the continuing exchanges, too often made ignoring or misinterpreting years of research regarding the importance of co-parenting and the involvement of fathers and other carers. One of the great contributions of child and adolescent mental health professionals has been the drawing of attention to the importance of family processes and systemic thinking, yet in relation to parenting, this seems to have been increasingly overlooked in recent years with an increased focus on attachment or social learning inspired approaches for a single parent-child dyad. In this issue of the JCPP, in a thorough and timely review, Catherine Panter-Brick and colleagues call for a clear change to the way parenting programmes are considered, studied and implemented. In this commentary, we reflect on this call and look at three challenges for CAMHS professionals. PMID- 25135766 TI - Short-term safety and efficacy of calcium montmorillonite clay (UPSN) in children. AB - Recently, an association between childhood growth stunting and aflatoxin (AF) exposure has been identified. In Ghana, homemade nutritional supplements often consist of AF-prone commodities. In this study, children were enrolled in a clinical intervention trial to determine the safety and efficacy of Uniform Particle Size NovaSil (UPSN), a refined calcium montmorillonite known to be safe in adults. Participants ingested 0.75 or 1.5 g UPSN or 1.5 g calcium carbonate placebo per day for 14 days. Hematological and serum biochemistry parameters in the UPSN groups were not significantly different from the placebo-controlled group. Importantly, there were no adverse events attributable to UPSN treatment. A significant reduction in urinary metabolite (AFM1) was observed in the high dose group compared with placebo. Results indicate that UPSN is safe for children at doses up to 1.5 g/day for a period of 2 weeks and can reduce exposure to AFs, resulting in increased quality and efficacy of contaminated foods. PMID- 25135768 TI - Patients' preferences: a discrete-choice experiment for treatment of non-small cell lung cancer. AB - OBJECTIVE: Lung cancer is a major cause of cancer-related deaths and thus represents a global health problem. According to World Health Organization (WHO) estimates, approximately 1.37 million people die each year from lung cancer. Different therapeutic approaches as well as several treatment options exist. To date decisions on which therapies to use have largely been made by clinical experts. Comparative preference studies show that underlying weighting of treatment goals by experts is not necessarily congruent with the preferences of affected patients. AIM AND METHODS: The aim of this empirical study was to ascertain patient preferences in relation to treatment of non-small-cell lung cancer (NSCLC). After identification of patient-relevant treatment attributes via literature review and qualitative interviews(ten) a discrete-choice experiment including seven patient-relevant attributes was conducted using a fractional factorial NGene-design. Statistical data analysis was performed using latent class models. RESULTS: The qualitative part of this study identified outcome measures related to efficacy, side effects and mode of administration. A total of 211 NSCLC patients (N = 211) participated in the computer-assisted personal interview. A clear preference for an increase in "progression-free survival" (coef.: 1.087) and a reduction of "tumor-associated symptoms"(cough, shortness of breath and pain); coef.: 1.090) was demonstrated, followed by the reduction of side effects: "nausea and vomiting" (coef.: 0.605); "rash" (coef.: 0.432); "diarrhea" (coef.: 0.427); and, "tiredness and fatigue" (coef.: 0.423). The "mode of administration" was less important for participants (coef.: 0.141). CONCLUSION: Preference measurement showed "progression-free survival" and "tumor associated symptoms" had a significant influence on the treatment decision. Subgroup analysis revealed that the importance of "progression-free survival" increases with increased therapy experience. Based on the presented results therapies can be designed, assessed and chosen on the basis of patient-oriented findings. As such, more effective and efficient care of patients can be achieved and benefits increased. PMID- 25135769 TI - Recommendation of rotavirus vaccination and herd effect: a budget impact analysis based on German health insurance data. AB - The objective of this study was to assess the budget impact and health effects of introducing rotavirus (RV) vaccination in Saxony, Germany, from a health insurance perspective. Special emphasis is given to the herd effect. We analyzed direct medical and non-medical costs of RV infection for Social Health Insurance between 2007 and 2010 based on 360,000 routine data observations from the AOK PLUS for children below 5 years of age. We compared the actual annual number of RV cases (vaccination scenario) with the number derived from 2005 (no vaccination, base case scenario). The vaccination coverage rate has increased from 5% to 61% between 2007 and 2010. The number of RV cases decreased by 21% from 32,274 in 2007 to 25,614 in 2010. Based on vaccination coverage, the total cost savings per 1,000 children due to RV vaccination was estimated to be 39,686 Euros. The overall share of outpatient costs was 60%. Mean gross cost savings were expected to be 304 Euros per avoided case. The net cost savings were expected to be 19 Euros per avoided case. About 59% of total savings was due to herd protection resulting from increasing vaccine rates. The herd effect per avoided case increased with increasing vaccine coverage. Incidence of RV cases, vaccination costs and days absent from work were sensitive parameters. This retrospective analysis showed that the increase in RV vaccination coverage in Saxony has been budget neutral if not cost saving for sick funds. PMID- 25135771 TI - Physico-chemical properties and cytotoxic potential of Cordyceps sinensis metabolites. AB - This study was conducted to estimate the antioxidant activities, biochemical properties and biological activities of one of the entomopathogenic fungi, Cordyceps sinensis. Analysis of fungal metabolites indicated that the most abundant free sugar was glucose; the highest component of organic acids was citric acid from 10-day culture medium and the glutamate was the predominant amino acid observed from 3-day culture medium. Maximum total polyphenols and flavonoids were detected in the 15-day culture medium. For cytotoxicity test, three cancer cell lines, HepG2 (liver), MCF-7 (breast) and A549 (lung) were used. The IC50 values of the highest toxicity of HepG2 cell lines were observed from 10 day cultured medium, whereas the highest toxicity of MCF-7 and A549 was observed on 5-day cultured medium. This is the first study reporting on the strong antioxidant and cytotoxic potential of C. sinensis. Culture medium of C. sinensis may thus be used as an effective antioxidant and anticancer treatment of natural origin. PMID- 25135770 TI - Trends in red blood cell transfusion and 30-day mortality among hospitalized patients. AB - BACKGROUND: Blood conservation strategies have been shown to be effective in decreasing red blood cell (RBC) utilization in specific patient groups. However, few data exist describing the extent of RBC transfusion reduction or their impact on transfusion practice and mortality in a diverse inpatient population. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study using comprehensive electronic medical record data from 21 medical facilities in Kaiser Permanente Northern California. We examined unadjusted and risk-adjusted RBC transfusion and 30-day mortality coincident with implementation of RBC conservation strategies. RESULTS: The inpatient study cohort included 391,958 patients who experienced 685,753 hospitalizations. From 2009 to 2013, the incidence of RBC transfusion decreased from 14.0% to 10.8% of hospitalizations; this change coincided with a decline in pretransfusion hemoglobin (Hb) levels from 8.1 to 7.6 g/dL. Decreased RBC utilization affected broad groups of admission diagnoses and was most pronounced in patients with a nadir Hb level between 8 and 9 g/dL (n = 73,057; 50.8% to 19.3%). During the study period, the standard deviation of risk-adjusted RBC transfusion incidence across hospitals decreased by 44% (p < 0.001). Thirty day mortality did not change significantly with declines in RBC utilization in patient groups previously studied in clinical trials nor in other subgroups. CONCLUSIONS: After the implementation of blood conservation strategies, RBC transfusion incidence and pretransfusion Hb levels decreased broadly across medical and surgical patients. Variation in RBC transfusion incidence across hospitals decreased from 2010 to 2013. Consistent with clinical trial data, more restrictive transfusion practice did not appear to impact 30-day mortality. PMID- 25135772 TI - Neonatal lethality of neural crest cell-specific Rest knockout mice is associated with gastrointestinal distension caused by aberrations of myenteric plexus. AB - RE1-silencing transcription factor (REST), also known as NRSF (neuron-restrictive silencer factor), is a well-known transcriptional repressor of neural genes. Rest null mice have embryonic lethality which prevents further investigations of the functions of the Rest gene in vivo. We studied neonatal but not embryonic lethality that was characterized by gastrointestinal tract dilation in the neural crest cell (NCC)-specific Rest conditional knockout (CKO) mice. While no histological abnormalities except the thinning of the digestive tract as a consequence of the gas accumulation were found in the digestive tract of the mutant mice, they do not have proper gastric retention after oral dye administration and the reduction of acetylcholinesterase (AChE) activity in NCC derived myenteric plexus in the stomach was detected. High CO2 concentration in the dilated digestive tract of the Rest CKO mice indicates a failure of gut function by underdeveloped cholinergic transmission in the enteric nervous system. The observed gastrointestinal distension phenotype provides a model for understanding the genetic and molecular basis of NCC defects in humans. PMID- 25135773 TI - Does MESNA application make sense in chronic otitis media surgery? PMID- 25135774 TI - Delivering evidence-based treatments for child attention-deficit/hyperactivity disorder (ADHD) in the context of parental ADHD. AB - Behavioral parent training (BPT) and stimulant medications are efficacious treatments for child attention-deficit/hyperactivity disorder (ADHD); however, there is some evidence to suggest that parental ADHD may reduce the efficacy of both treatment modalities. This review paper summarizes the literature related to the evidence-based behavioral and pharmacological treatment of child ADHD in the context of parental ADHD. We also review the literature on the effects of treating parents' ADHD symptoms on parenting and child behavior outcomes. Although the literature is small and inconsistent, studies suggest that medicating parents' ADHD symptoms may or may not be sufficient in demonstrating desired improvements in parenting and child behavioral outcomes. Therefore, interventions targeting both parent and child ADHD, when both are present, are likely needed to improve parent-child interactions and family functioning. Ongoing studies using a multimodal approach are discussed. PMID- 25135775 TI - Internally displaced "victims of armed conflict" in Colombia: the trajectory and trauma signature of forced migration. AB - While conflict-induced forced migration is a global phenomenon, the situation in Colombia, South America, is distinctive. Colombia has ranked either first or second in the number of internally displaced persons for 10 years, a consequence of decades of armed conflict compounded by high prevalence of drug trafficking. The displacement trajectory for displaced persons in Colombia proceeds through a sequence of stages: (1) pre-expulsion threats and vulnerability, (2) expulsion, (3) migration, (4) initial adaptation to relocation, (5) protracted resettlement (the end point for most forced migrants), and, rarely, (6) return to the community of origin. Trauma signature analysis, an evidence-based method that elucidates the physical and psychological consequences associated with exposures to harm and loss during disasters and complex emergencies, was used to identify the psychological risk factors and potentially traumatic events experienced by conflict-displaced persons in Colombia, stratified across the phases of displacement. Trauma and loss are experienced differentially throughout the pathway of displacement. PMID- 25135776 TI - Strategies for successful aging: a research update. AB - Population aging is an enormous public health issue and there is clear need for strategies to maximize opportunities for successful aging. Many psychiatric illnesses are increasingly thought to be associated with accelerated aging, therefore emerging data on individual and policy level interventions that alter typical aging trajectories are relevant to mental health practitioners. Although the determinants and definition of successful aging remain controversial, increasing data indicate that psychiatric illnesses directly impact biological aging trajectories and diminish lifestyle, psychological, and socio-environmental factors that seem to reduce risk of morbidity and mortality. Many interventions designed to enhance the normal course of aging may be adjunctive approaches to management of psychiatric illnesses. We highlight recent data on interventions seeking to promote healthy aging, such as cognitive remediation, physical activity, nutrition, and complementary and alternative treatments for older people with and without psychiatric illnesses. PMID- 25135777 TI - Determining the causes and consequences of nicotine dependence: emerging genetic research methods. AB - Tobacco use remains the leading cause of preventable death worldwide. Establishing the genetic aetiology of tobacco use and dependence is an important first step in understanding the neurobiological mechanisms of tobacco use, and in turn the development of effective treatments. In addition, whilst the effects of tobacco use on a broad range of physical illnesses (e.g. lung cancer, respiratory disease, cardiovascular disease) are now well-established, the causal effects of tobacco use on a number of other outcomes remains to be established. Determining the causes and consequences of tobacco use therefore continues to be both a scientific and a public health priority. Here we review emerging methods in genetic research that allow stronger causal inferences to be drawn from observational data. PMID- 25135778 TI - Using stimulants to treat ADHD-related emotional lability. AB - Emotional lability, or sudden strong shifts in emotion, commonly occurs in youth with attention-deficit/hyperactivity disorder. Although these symptoms are impairing and disruptive, relatively little research has addressed their treatment, likely due to the difficulty of reliable and valid assessment. Promising signals for symptom improvement have come from recent studies using stimulants in adults, children and adolescents. Similarly, neuroimaging studies have begun to identify neurobiological mechanisms underlying stimulants' impact on emotion regulation capacities. Here, we review these recent clinical and neuroimaging findings, as well as neurocognitive models for emotional lability in ADHD, issues of relevance to prescribers and the important role of psychiatric comorbidity with treatment choices. PMID- 25135779 TI - Managing the risks of ADHD treatments. AB - Pharmacotherapy of attention deficit-hyperactivity disorder (ADHD) is a well established and effective treatment modality. However, ADHD medications are not without side effects. Understanding the prevalence of adverse events and effective management of risks associated with stimulants and other medications used to treat ADHD is central to broad applicability and effective treatment. This review discusses the literature on the prevalence of adverse events and management strategies employed. We searched online MEDLINE/PubMed and Cochrane databases for articles using several keywords relating to adverse events associated with ADHD medication management. We discuss the relevant data on the significance and prevalence of side effects and adverse events, highlight recent updates in the field, and suggest approaches to clinical management. PMID- 25135780 TI - Personality disorder classification: stuck in neutral, how to move forward? AB - An "Alternative DSM-5 Model for Personality Disorders" was published in Sect. III of DSM-5, while the identical categories and criteria from DSM-IV for the personality disorders (PDs) are in Sect. II. Given strong shifts from categorical diagnoses toward dimensional representations in psychiatry, how did the PDs end up "stuck in neutral," with the flawed DSM-IV model perpetuated? This article reviews factors that influenced the development of the new model and data to encourage and facilitate its use by clinicians. These include recognizing 1) a dimensional structure for psychopathology for which personality may be foundational; 2) a consensus on the structure of normal and abnormal personality; 3) the clinical significance of personality; 4) PD-specific severity required to establish disorder; 5) disruption, discontinuity, and perceived clinical utility of the Alternative Model may not be problems; and 6) a way forward involving collaborative research on neurobiological and psychosocial processes, treatment planning, and outcomes. PMID- 25135781 TI - Bereavement: course, consequences, and care. AB - This paper discusses each of several potential consequences of bereavement. First, we describe ordinary grief, followed by a discussion of grief gone awry, or complicated grief (CG). Then, we cover other potential adverse outcomes of bereavement, each of which may contribute to, but are not identical with, CG: general medical comorbidity, mood disorders, post-traumatic stress disorder, anxiety, and substance use. PMID- 25135782 TI - Circadian clock and stress interactions in the molecular biology of psychiatric disorders. AB - Many psychiatric disorders are characterized by circadian rhythm abnormalities, including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders. PMID- 25135783 TI - The significance of mixed states in depression and mania. AB - The DSM-5 definition of mixed features "specifier" of manic, hypomanic and major depressive episodes captures sub-syndromal non-overlapping symptoms of the opposite pole, experienced in bipolar (I, II, and not otherwise specified) and major depressive disorders. This combinatory model seems to be more appropriate for less severe forms of mixed state, in which mood symptoms are prominent and clearly identifiable. Sub-syndromal depressive symptoms have been frequently reported to co-occur during mania. Similarly, manic or hypomanic symptoms during depression resulted common, dimensionally distributed, and recurrent. The presence of mixed features has been associated with a worse clinical course and high rates of comorbidities including anxiety, personality, alcohol and substance use disorders and head trauma or other neurological problems. Finally, mixed states represent a major therapeutic challenge, especially when you consider that these forms tend to have a less favorable response to drug treatments and require a more complex approach than non-mixed forms. PMID- 25135784 TI - Sleep and substance use disorders: an update. AB - Substance use disorders (SUD) are common and individuals who suffer from them are prone to relapse. One of the most common consequences of the use of and withdrawal from substances of abuse is sleep disturbance. Substances of abuse affect sleep physiology, including the neurotransmitter systems that regulate the sleep-wake system. Emerging research now highlights an interactive effect between sleep disorders and substance use. New findings in alcohol and sleep research have utilized sophisticated research designs and expanded the scope of EEG and circadian rhythm analyses. Research on marijuana and sleep has progressed with findings on the effects of marijuana withdrawal on objective and subjective measures of sleep. Treatment studies have focused primarily on sleep in alcohol use disorders. Therapies for insomnia in cannabis disorders are needed. Future research is poised to further address mechanisms of sleep disturbance in alcoholics and the effect of medical marijuana on sleep and daytime functioning. PMID- 25135786 TI - Sentinel node mapping using hysteroscopic injection of indocyanine green and laparoscopic near-infrared fluorescence imaging in endometrial cancer staging. AB - Herein is presented a technique for minimally invasive sentinel node mapping. The patient had apparently early stage endometrial cancer. Sentinel node mapping was performed using a hysteroscopic injection of indocyanine green followed by laparoscopic sentinel node detection via near-infrared fluorescence. This technique ensures delineation of lymphatic drainage from the tumor area, thus achieving accurate detection of sentinel nodes. PMID- 25135785 TI - Species and gene divergence in Littorina snails detected by array comparative genomic hybridization. AB - BACKGROUND: Array comparative genomic hybridization (aCGH) is commonly used to screen different types of genetic variation in humans and model species. Here, we performed aCGH using an oligonucleotide gene-expression array for a non-model species, the intertidal snail Littorina saxatilis. First, we tested what types of genetic variation can be detected by this method using direct re-sequencing and comparison to the Littorina genome draft. Secondly, we performed a genome-wide comparison of four closely related Littorina species: L. fabalis, L. compressa, L. arcana and L. saxatilis and of populations of L. saxatilis found in Spain, Britain and Sweden. Finally, we tested whether we could identify genetic variation underlying "Crab" and "Wave" ecotypes of L. saxatilis. RESULTS: We could reliably detect copy number variations, deletions and high sequence divergence (i.e. above 3%), but not single nucleotide polymorphisms. The overall hybridization pattern and number of significantly diverged genes were in close agreement with earlier phylogenetic reconstructions based on single genes. The trichotomy of L. arcana, L. compressa and L. saxatilis could not be resolved and we argue that these divergence events have occurred recently and very close in time. We found evidence for high levels of segmental duplication in the Littorina genome (10% of the transcripts represented on the array and up to 23% of the analyzed genomic fragments); duplicated genes and regions were mostly the same in all analyzed species. Finally, this method discriminated geographically distant populations of L. saxatilis, but we did not detect any significant genome divergence associated with ecotypes of L. saxatilis. CONCLUSIONS: The present study provides new information on the sensitivity and the potential use of oligonucleotide arrays for genotyping of non-model organisms. Applying this method to Littorina species yields insights into genome evolution following the recent species radiation and supports earlier single-gene based phylogenies. Genetic differentiation of L. saxatilis ecotypes was not detected in this study, despite pronounced innate phenotypic differences. The reason may be that these differences are due to single-nucleotide polymorphisms. PMID- 25135787 TI - Characterization of glycerophosphoethanolamine ethanolaminephosphodiesterase from Streptomyces sanglieri. AB - Streptomyces sanglieri extracellularly produces a glycerophosphoethanolamine ethanolaminephosphodiesterase (GPE-EP). The gene encoding the enzyme was found to consist of a 2124-bp ORF, which codes for an N-terminal 48 residue signal peptide required for secretion and a 660 amino acid mature protein with a calculated molecular mass of 72,918 Da. The maximum activity for sn-glycero-3 phosphoethanolamine (GPE) was found at pH 8.4 and 65 degrees C in the presence of 0.1% (w/v) Triton X-100. The enzyme was activated in the presence of 2 mM EDTA; however, Zn(2+) remarkably inhibited activity. During the hydrolysis of GPE at 65 degrees C and pH 8.4, the apparent Vmax, turnover number (kcat) and Km were determined to be 0.430 mmol min(-1) mg-protein(-1), 522 s(-1) and 0.785 mM, respectively. The enzyme exhibited specificity toward GPE and hydrolyzed ethanolamine-type substrates such as 1,2-dihexanoyl-sn-glycero-3 phosphoethanolamine, lysophosphatidylethanolamine and ethanolamine lysoplasmalogen, but not 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine. Moreover, the enzyme showed no activity toward other phospholipids, such as glycerophospholipids and plasmalogens, and sn-glycero-3-phosphodiesters except for sn-glycero-3-phosphoglycerol, suggesting that GPE-EP is not a phospholipase C (PLC). However, the amino acid sequence of GPE-EP shows 86% identity to that of PLC from Streptomyces sp. SirexAA-E (UniProt accession no. G2NFN1). Recombinant GPE-EP was functionally expressed in Escherichia coli using pET-24a(+). GPE hydrolysis by GPE-EP may represent a new pathway for phosphatidylethanolamine metabolism. PMID- 25135788 TI - Expression profile based gene clusters for ischemic stroke detection. AB - In microarray studies alterations in gene expression in circulating leukocytes have shown utility for ischemic stroke diagnosis. We studied forty candidate markers identified in three gene expression profiles to (1) quantitate individual transcript expression, (2) identify transcript clusters and (3) assess the clinical diagnostic utility of the clusters identified for ischemic stroke detection. Using high throughput next generation qPCR 16 of the 40 transcripts were significantly up-regulated in stroke patients relative to control subjects (p<0.05). Six clusters of between 5 and 7 transcripts were identified that discriminated between stroke and control (p values between 1.01e-9 and 0.03). A 7 transcript cluster containing PLBD1, PYGL, BST1, DUSP1, FOS, VCAN and FCGR1A showed high accuracy for stroke classification (AUC=0.854). These results validate and improve upon the diagnostic value of transcripts identified in microarray studies for ischemic stroke. The clusters identified show promise for acute ischemic stroke detection. PMID- 25135789 TI - Expression of the lymphatic marker podoplanin (D2-40) in human fetal eyes. AB - During human ocular development, expression of proteins varies in different maturation stages. This study aims to characterize structures in human fetal eyes stained by the lymphatic marker podoplanin (D2-40) with emphasis on the stage of maturation and the presence of intraocular lymphatic structures. Formalin-fixed paraffin-embedded eyes from 40 human fetuses between 10 and 38 weeks of gestation (WoG) were investigated. Immunohistochemical stains were performed for D2-40, LYVE-1 as a secondary lymphatic marker, and CD34 as a control for endothelial reactivity. A semiquantitative analysis of antigen expression in different segments of the eye was performed by light microscopy. The intensity of antigen expression was graded with a score ranging from 0 to 3. Podoplanin expression was found with a variable intensity in 97.5% of the eyes, in particular in lymphatic vessels of the conjunctiva (n = 26), conjunctival and corneal epithelium (n = 33), corneal endothelium (n = 4), trabecular meshwork (n = 28), and optic nerve sheaths (n = 23). A slight, equivocal staining reaction was noted in the choroid (n = 14). There was a correlation of antigen reactivity and the gestational age for corneal endothelial reactivity in earlier gestational stages (p = 0.003) and trabecular meshwork in older eyes (p = 0.031). D2-40 positive Muller cells were detected in two eyes >=32 WoG. Thus, aside from conjunctival lymphatic vessels, podoplanin was expressed in several structures of the human fetal eye and the ocular adnexae at different gestational stages. Podoplanin positive structures were also found in the choroid and the chamber angle. However, lymphatic vessels or its progenitors could not be unequivocally identified in intraocular structures during 10-38 weeks of gestation. There is no evidence from our data that transient intraocular lymphactics develop in the fetal eye between 10 and 38 weeks of gestation. PMID- 25135790 TI - Micro-fractional epidermal powder delivery for improved skin vaccination. AB - Skin vaccination has gained increasing attention in the last two decades due to its improved potency compared to intramuscular vaccination. Yet, the technical difficulty and frequent local reactions hamper its broad application in the clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is developed to facilitate skin vaccination and minimize local adverse effects. EPD is based on ablative fractional laser or microneedle treatment of the skin to generate microchannel (MC) arrays in the epidermis followed by topical application of powder drug/vaccine-coated array patches to deliver drug/vaccine into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and model antigen ovalbumin (OVA) into murine, swine, and human skin within 1h. EPD of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID) injection and was much more efficient than tape stripping in both delivery efficiency and immune responses. Strikingly, the micro-fractional delivery significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine, leading to complete skin recovery. In contrast, ID injection induced severe local reactions that persisted for weeks. While reducing local reactogenicity, EPD of OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID injection. EPD of vaccinia virus encoding OVA induced significantly higher and long-lasting interferon gamma-secreting CD8+ T cells than ID injection. In conclusion, EPD represents a promising technology for needle-free, painless skin vaccination with reduced local reactogenicity and at least sustained immunogenicity. PMID- 25135791 TI - Relations between acoustic cavitation and skin resistance during intermediate- and high-frequency sonophoresis. AB - Enhanced skin permeability is known to be achieved during sonophoresis due to ultrasound-induced cavitation. However, the mechanistic role of cavitation during sonophoresis has been extensively investigated only for low-frequency (LFS, <100 kHz) applications. Here, mechanisms of permeability-enhancing stable and inertial cavitation were investigated by passively monitoring subharmonic and broadband emissions arising from cavitation isolated within or external to porcine skin in vitro during intermediate- (IFS, 100-700 kHz) and high-frequency sonophoresis (HFS, >1 MHz). The electrical resistance of skin, a surrogate measure of the permeability of skin to a variety of compounds, was measured to quantify the reduction and subsequent recovery of the skin barrier during and after exposure to pulsed (1 second pulse, 20% duty cycle) 0.41 and 2.0 MHz ultrasound over a range of acoustic powers (0-21.7 W) for 30 min. During IFS, significant skin resistance reductions and acoustic emissions from cavitation were measured exclusively when cavitation was isolated outside of the skin. Time-dependent skin resistance reductions measured during IFS correlated significantly with subharmonic and broadband emission levels. During HFS, significant skin resistance reductions were accompanied by significant acoustic emissions from cavitation measured during trials that isolated cavitation activity either outside of skin or within skin. Time-dependent skin resistance reductions measured during HFS correlated significantly greater with subharmonic than with broadband emission levels. The reduction of the skin barrier due to sonophoresis was reversible in all trials; however, effects incurred during IFS recovered more slowly and persisted over a longer period of time than HFS. These results quantitatively demonstrate the significance of cavitation during sonophoresis and suggest that the mechanisms and post-treatment longevity of permeability enhancement due to IFS and HFS treatments are different. PMID- 25135793 TI - Addition of recommendations for the use of recombinant human thrombomodulin to the "Expert consensus for the treatment of disseminated intravascular coagulation in Japan". PMID- 25135792 TI - Intercalating quaternary nicotinamide-based poly(amido amine)s for gene delivery. AB - In the development of potent polymeric gene carriers for gene therapy, a good interaction between the polymer and the nucleotide is indispensable to form small and stable polyplexes. Polymers with relatively high cationic charge density are frequently used to provide these interactions, but high cationic charge is usually associated with severe cytotoxicity. In this study an alternative, nucleotide specific binding interaction based on intercalation was investigated to improve polymer/pDNA complex formation. For this purpose bioreducible poly(amido amine) copolymers (p(CBA-ABOL/Nic)) were synthesized with different degrees of intercalating quaternary nicotinamide (Nic) groups and amide substituted derivatives in their side chains. The quaternary nicotinamide group was chosen as intercalating moiety because this group is part of the naturally occurring NAD+ coenzyme and is therefore expected to be non-toxic and non carcinogenic. The presence of the quaternary nicotinamide moieties in the poly(amido amine) copolymers showed to effectively promote self-assembled polyplex formation already at low polymer/DNA ratios and results in decreased polyplex size and increased stability of the polyplexes. Furthermore, in contrast to the primary amine functionalized analogs the quaternary nicotinamide polymers showed to be non-hemolytic, indicating their compatibility with cell membranes. Polymers with 25% of Nic in the side chains induced GFP expressions of about 4-5 times that of linear PEI, which is comparable with p(CBA-ABOL), the parent PAA without Nic, but at a two- to fourfold lower required polymer dose. N-phenylation of the nicotinamide functionality even further reduces the required polymer dose to form stable polyplexes, which is a major improvement for these kinds of cationic polymers. PMID- 25135794 TI - Treatment patterns of venous thromboembolism in a real-world population: the Q VTE study cohort. AB - BACKGROUND: Few studies have assessed treatment patterns of acute venous thromboembolism (VTE) in a real-world population. We aimed to describe anticoagulant treatment patterns for acute VTE using healthcare databases of Quebec, Canada. METHODS: We used linked healthcare databases of the province of Quebec, Canada to identify all incident cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) between 2000 and 2009. We formed two patient cohorts, one with definite cases (definite VTE cohort, N=40,776) and the other including cases with definite or probable VTE (any VTE cohort, N=54,803) that were followed until death, end of health coverage, or end of study (December 31, 2009). RESULTS: In the definite cohort, 73.6% of subjects were dispensed an anticoagulant following the diagnosis of VTE. Of those who were dispensed a vitamin K antagonist (VKA), median duration of use was 61days (interquartile range 89). VKA initiation was more likely in patients with pulmonary embolism than deep vein thrombosis alone (HR 1.62, 95% CI (1.58-1.66)). Among outpatients, those managed initially in the outpatient setting were less likely to initiate VKA therapy (HR 0.75, 95% CI (0.68-0.77)), while those requiring admission to hospital for VTE management were more likely to initiate (HR 1.81, 95% CI (1.76-1.87)). Findings were similar in the any VTE cohort. CONCLUSION: Our study describes VTE treatment patterns in a real-world setting and suggests that there may be important gaps. These may include significant numbers of patients who did not initiate oral anticoagulant therapy, particularly in the outpatient setting, and shorter duration of oral anticoagulant use than recommended. PMID- 25135795 TI - Increased activation of blood coagulation in pregnant women with the Factor V Leiden mutation. AB - BACKGROUND: The risk of venous thromboembolism is enhanced in pregnant carriers of the Factor V Leiden mutation. The primary aim of the study was to compare prothrombin fragments 1+2, soluble fibrin and D-dimer levels in pregnant Factor V Leiden mutation carriers with those in non-carriers. Secondary aims were to evaluate whether these biomarkers could predict placenta-mediated complications or venous thromboembolism, and to study blood coagulation after caesarean section with thromboprophylaxis and after vaginal delivery without thromboprophylaxis. MATERIAL/METHODS: Prothrombin fragments 1+2, soluble fibrin and D-dimer levels were studied longitudinally in 476 carriers with singleton pregnancies from gestational weeks 23-25 until 8-10 weeks postpartum. RESULTS: Prothrombin fragments 1+2 and D-dimer levels gradually increased during pregnancy. D-dimer levels were higher in carriers, both during pregnancy and puerperium, compared to non-carriers. D-dimer levels above 0.5mg/l were found in about 30% and 20% of the heterozygous carriers at 4-5 and 8-10 weeks postpartum, respectively. Soluble fibrin levels were mainly unchanged during pregnancy, with no difference between carriers and non-carriers. Biomarker levels were similar in carriers with uncomplicated and complicated pregnancies. CONCLUSION: Higher D-dimer levels indicate increased blood coagulation and fibrinolysis activity in carriers. The high proportion of carriers with D-dimer levels exceeding 0.5mg/l postpartum must be considered when assessing the probability of venous thromboembolism. Large overlaps in biomarker levels in normal and complicated pregnancies suggest that these biomarkers cannot be used as predictors. Thromboprophylaxis following caesarean section may prevent increased activation of blood coagulation. PMID- 25135796 TI - Global platelet hyperreactivity and elevated C-reactive protein levels predict long term mortality in STEMI patients. AB - BACKGROUND: Data on long term - more than 1-year - prognostic value of global platelet reactivity (G-HPR) - by adenosine diphosphate (ADP) and arachidonic acid (AA) - in patients with STEMI undergoing PCI are limited. High C-reactive protein (CRP) levels have been suggested to be associated with post-PCI atherothrombotic events. Our aim was to evaluate the long-term prognostic impact of G-HPR and CRP levels in STEMI patients. METHODS AND RESULTS: We evaluated 494 STEMI patients (366 M/128 F; age: 65.8 +/- 12.4 yrs) undergoing PCI with stent implantation. At a median follow-up of 2.3 years (1.09-4.06), in 58 patients we documented cardiovascular death (11.7%). Platelet reactivity was assessed by light transmission aggregometry by 1mM AA (AA-LTA) and 10 microM ADP (ADP-LTA). By the ROC curve analysis, 17%, 52% and 12 mg/L were found to be the values of AA-LTA, ADP-LTA and CRP associated with the highest specificity and sensitivity for death. G-HPR was defined as the presence of both AA-LTA >= 17% and ADP-LTA >= 52%. At Cox regression analysis adjusted for age, sex, cardiovascular risk factors, multivessel disease, ejection fraction, renal insufficiency, G-HPR and elevated CRP levels were associated with long-term mortality [HR=1.78 (95%CI 1.04 3.03), p=0.036 and HR=2.91 (1.54-5.52, p=0.001), respectively]. The contemporary presence of G-HPR and elevated CRP levels was associated with the highest risk of death [HR=5.1 (95%CI 1.9-13.4), p=0.001]. CONCLUSION: G-HPR and CRP are independent long-term prognostic markers in STEMI patients. The contemporary presence of G-HPR and CRP identifies a subgroup of patients at significantly higher risk of cardiovascular death. PMID- 25135797 TI - Sri Lankan cassava mosaic virus replication associated protein (Rep) triggers transposition of IS426 in Agrobacterium. AB - We report a high rate of IS426 transposition in Agrobacterium tumefaciens in the presence of the Sri Lankan cassava mosaic virus (SLCMV) replication associated protein gene (Rep). Upon conjugal transfer of the binary plasmid pCam-SLCMV-Rep with the SLCMV Rep gene in the sense orientation under the transcriptional control of the Cauliflower mosaic virus (CaMV) 35S promoter into the A. tumefaciens vir helper strain EHA105, the binary plasmid size increased in all 15 transconjugants studied. Southern blot analysis of the transconjugants with the binary plasmid probe revealed that the 35S promoter and its proximal sequences in the T-DNA were rearranged. The rearranged sequences harboured the 1.3-kb IS426 element of A. tumefaciens. Conjugal mobilisation of the binary plasmid pCam-SLCMV asRep, with the SLCMV Rep gene in antisense orientation, did not cause DNA rearrangement in EHA105. A mutated SLCMV Rep, in which a frame shift mutation caused retention of only 27 of the 351 amino acids, did not cause IS426 transposition in A. tumefaciens. These findings show that the multifunctional begomoviral Rep protein of SLCMV triggers transposition of IS426 in Agrobacterium. PMID- 25135798 TI - Use of prescription drugs and future delinquency among adolescent offenders. AB - Non-medical use of prescription drugs (NMUPD) by adolescents is a significant public health concern. The present study investigated the profile of NMUPD in 1349 adolescent offenders from the Pathways to Desistance project, and whether NMUPD predicted future delinquency using longitudinal data. Results indicated that increased frequency and recency of NMUPD in adolescent offenders are related to some demographic factors, as well as increased risk for violence exposure, mental health diagnoses, other drug use, and previous delinquency, suggesting that severity of NMUPD is important to consider. However, ANCOVA analyses found that NMUPD was not a significant predictor of drug-related, non-aggressive, or aggressive delinquency 12 months later beyond other known correlates of delinquency. Age, sex, exposure to violence, lower socioeconomic status, more alcohol use, and having delinquency histories were more important than NMUPD in predicting future delinquency. These findings suggest that although NMUPD is an important risk factor relating to many correlates of delinquency, it does not predict future delinquency beyond other known risk factors. PMID- 25135799 TI - Refugees, humanitarian aid and the right to decline vaccinations. AB - Recent instances of governments and others refusing humanitarian assistance to refugees and IDPs (internally-displaced persons) unless they agreed to polio immunization for their children raise difficult ethical challenges. The authors argue that states have the right and a responsibility to require such vaccinations in instances where the serious vaccine-preventable disease(s) at issue threaten others, including local populations, humanitarian workers, and others in camps or support settings. PMID- 25135801 TI - Using the Peng flap for a wide dorsal nasal defect. AB - Reconstructions of large surgical defects of the central part of the nose pose a challenge for the surgeon due to its cosmetically prominent location. Treatment options include second intention healing, full-thickness skin grafts and various local flaps. In the present case the "Peng flap" was used for the reconstruction of a 3.1 * 7 cm sized deep defect of the convex curve of the central nasal area in a 66-year-old woman. The Peng flap was performed as single-stage procedure without complications. Good cosmetic outcome was provided by the use of adjacent skin from the lax perinasal area, the placement of the scar lines between facial cosmetic units, and the excellent tissue match for the sebaceous nasal skin. Considering the few complications of a single-stage procedure associated with an excellent aesthetic outcome, the Peng flap should be considered not only as an effective choice for reconstruction of the cosmetically complex midline nasal tip but also the convex curve of the central nose. PMID- 25135800 TI - Motives for participating in a web-based nutrition cohort according to sociodemographic, lifestyle, and health characteristics: the NutriNet-Sante cohort study. AB - BACKGROUND: In traditional epidemiological studies, participants are likely motivated by perceived benefits, feelings of accomplishment, and belonging. No study has explored motives for participation in a Web-based cohort and the associated participant characteristics, although such information is useful for enhancing recruitment and improving cohort retention. OBJECTIVE: We aimed to evaluate the relationships between motives for participation and sociodemographic, health, and lifestyle characteristics of participants in the NutriNet-Sante Web-based cohort, designed to identify nutritional risk or protective factors for chronic diseases. METHODS: The motives for participation were assessed using a specifically developed questionnaire administered approximately 2 years after baseline. A total of 6352 completed the motives questionnaire (43.34%, 6352/15,000 randomly invited cohort participants). We studied the associations between motives (dependent variables) and individual characteristics with multivariate multinomial logistic regression models providing odds ratios and 95% confidence intervals. RESULTS: In total, 46.45% (2951/6352) of participants reported that they would not have enrolled if the study had not been conducted on the Internet, whereas 28.75% (1826/6352) were not sure. Men (OR 1.21, 95% CI 1.04-1.42), individuals aged 26-35 years (OR 1.51, 95% CI 1.20-1.91), and obese participants (OR 1.30, 95% CI 1.02-1.65) were more inclined to be motivated by the Internet aspect. Compared with younger adults and managerial staff, individuals >55 years (OR 0.60, 95% CI 0.48-0.45) and employees/manual workers were less likely motivated by the Internet aspect (OR 0.77, 95% CI 0.63-0.92). Regarding reasons for participation, 61.37% (3898/6352) reported participating to help advance public health research on chronic disease prevention; 22.24% (1413/6352) to help advance nutrition-focused research; 6.89% (438/6352) in response to the call from the media, after being encouraged by a close friend/associate, or a medical provider. Individuals >45 years (vs younger participants) were more likely (OR 1.62, 95% CI 1.07-2.47), whereas overweight and obese participants (vs nonobese participants) were less likely to participate in the study for reasons related to helping public health research on chronic disease prevention (OR 0.72, 95% CI 0.58-0.89; OR 0.62, 95% CI 0.46-0.84; respectively). Exclusive public funding of the study was important for 67.02% (4257/6352) of the participants. Men (OR 1.37, 95% CI 1.17-1.61) and persons >55 years (OR 1.97, 95% CI 1.57-2.47) were more likely to consider the exclusive public funding as very important. CONCLUSIONS: The use of the Internet, the willingness to help advance public health research, and the study being publicly funded were key motives for participating in the Web-based NutriNet-Sante cohort. These motives differed by sociodemographic profile and obesity, yet were not associated with lifestyle or health status. These findings can help improve the retention strategies in Web-based cohorts, particularly during decisive study periods when principal exposure information is collected. PMID- 25135802 TI - Statin potency, LDL receptors and new onset diabetes. PMID- 25135803 TI - Effectiveness of pharmacist intervention in patients with chronic kidney disease. AB - BACKGROUND: Collaboration between pharmacists and physicians in the care of patients with chronic kidney disease (CKD) may improve the quality of drug dosage regimens that require adjustment according to the renal function. OBJECTIVE: To demonstrate that the intervention of a pharmacist in a monitoring program for patients with CKD improves the outcome of renal function in these patients. Setting A 330-bed regional referral hospital in the city of Murcia (Spain). METHOD: All patients with CKD and taking nephrotoxic medication admitted to the internal medicine service were included in the study. Depending on the department of the hospital to which the patients were admitted, they were assigned to an intervention or control group. In the control group, the renal function at the time of admission and discharge was measured. In the intervention group, in addition to measuring kidney function at the time of admission and at discharge, the patients were followed daily and recommendation for dose adjustment were made when nephrotoxic drugs were not properly dosed. MAIN OUTCOME MEASURE: Glomerular filtration rate on admission and at discharge. RESULTS: A total of 249 patients were included in the study, 124 in the control group and 125 in the intervention group. Significant differences were noted when comparing creatinine clearance (CrCl) between discharge and admission in both the control and intervention groups (5.1 +/- 0.9 vs. 6.4 +/- 1.0 p < 0.01). In a comparison of the observed improvement in the two groups, we found significant differences in adjusted relative CrCl according to sex, age and stage (19.9 [1.2-38.5] p < 0.05). When the disease was analyzed by stage, we observed significant differences that favored the intervention group in regards CrCl (3.1 +/- 2.1 vs. 7.9 +/- 3.8 p < 0.05) and relative CrCl (16.1 +/- 10.3 vs. 36.6 +/- 16.7) in stages 4-5. The rate of acceptance of the pharmacists' recommendations was 74 %. CONCLUSION: The implementation of a monitoring program for CKD patients was effective in the group in which monitoring was conducted, especially in patients with more advanced stage of CKD. PMID- 25135804 TI - Modified labels for long-term medications: influences on adherence, comprehension and preferences in Malaysia. AB - BACKGROUND: Inability to read instructions on drug labels has been identified among the Malaysian population since 1990's. OBJECTIVE: To assess the impact of font-enlarged and pictogram-incorporated labels used for long-term medications on patients' adherence, comprehension and preferences. SETTING: Outpatient pharmacy in one of the major general hospitals across Northern Malaysia. METHOD: This was a three-arm, randomized controlled trial. Outpatients with refill prescriptions of selected oral antihypertensive or antidiabetic medications were screened for eligibility. They were randomly allocated with standard (n = 35), font-enlarged (n = 40) or pictogram-incorporated (n = 35) labels. Assessment of baseline adherence scores using the 8-item Morisky Medication Adherence Scale, comprehension scores using a structured questionnaire and preferences was conducted upon recruitment. Follow-up telephone interviews were conducted after 4 weeks. MAIN OUTCOME MEASURE: The changes of patients' adherence and comprehension scores and their preferences. RESULTS: Within-group comparisons demonstrated an increase of total adherence scores after 4 weeks in all three groups (mean changes 0.35, 0.58 and 0.67; p = 0.029, 0.013 and 0.011, respectively). The repeatedly measured total comprehension score of pictogram-incorporated label group was significantly higher than baseline (mean change 0.37, p = 0.010). Two intervention groups obtained significantly higher scores for few items in both adherence and comprehension measurements after 4 weeks as compared with baselines. As indicated by F tests, three groups did not significantly differ in the changes of both total adherence and comprehension scores (p = 0.573 and 0.069, respectively) with the subjects' age adjusted. Elderlies and those with a higher number of morbidity preferred pictogram-incorporated label over font enlarged label. CONCLUSION: We did not find a significant change of both adherence and comprehension levels after the introduction of modified medication labels. However, on the basis of within-group comparisons, they may have positive influences on certain aspects of patients' adherence and comprehension. Variations in preferences may reflect the unique need of different subgroups in receiving written medication instructions. PMID- 25135805 TI - Impact of community pharmacist intervention discussing patients' beliefs to improve medication adherence. AB - BACKGROUND: Adherence to evidence based medicines in patients who have experienced a myocardial infarction remains low. Individual's beliefs towards their medicines are a strong predictor of adherence and may influence other factors that impact on adherence. OBJECTIVE: To investigate if community pharmacists discussing patients' beliefs about their medicines improved medication adherence at 12 months post myocardial infarction. SETTING: This study included 200 patients discharged from a public teaching hospital in Queensland, Australia, following a myocardial infarction. Patients were randomised into intervention (n = 100) and control groups (n = 100) and followed for 12 months. METHOD: All patients were interviewed between 5 to 6 weeks, at 6 and 12 months post discharge by the researcher using the repertory grid technique. This technique was used to elicit the patient's individualised beliefs about their medicines for their myocardial infarction. In the intervention group, patients' beliefs about their medicines were communicated by the researcher to their community pharmacist. The pharmacist used this information to tailor their discussion with the patient about their medication beliefs at designated time points (3 and 6 months post discharge). The control group was provided with usual care. MAIN OUTCOME MEASURE: The difference in non-adherence measured using a medication possession ratio between the intervention and control groups at 12 months post myocardial infarction. RESULTS: There were 137 patients remaining in the study (intervention group n = 72, control group n = 65) at 12 months. In the intervention group 29 % (n = 20) of patients were non-adherent compared to 25 % (n = 16) of patients in control group. CONCLUSION: Discussing patients' beliefs about their medicines for their myocardial infarction did not improve medication adherence. Further research on patients beliefs should focus on targeting non adherent patients whose reasons for their non-adherence is driven by their medication beliefs. PMID- 25135806 TI - Antimicrobial stewardship and linezolid. AB - BACKGROUND: Since 2002, linezolid, the first representative of the oxazolidinone class, has been widely prescribed, sometimes outside of approved indications. However, several cases of clinical outbreaks due to linezolid-resistant organisms have been reported, and its relatively high cost represents an economic challenge for hospital settings. OBJECTIVES: The aim of this study was to assess the impact of different actions conducted by an antimicrobial stewardship team (AST) to control over-prescription of linezolid with regard to the defined daily dose (DDD) per 1,000 inhabitants per day. SETTING: This work was conducted in a 1,495 bed hospital from 2009 to 2013. An AST, gathering the departments of pharmacy, microbiology, and infectious diseases, assessed the pertinence of linezolid use and associated effect on the prescriber. METHOD: A retrospective study was conducted throughout 2009. Three different evaluations were prospectively carried out, each for 3 months, between 2011 and 2013. MAIN OUTCOME MEASURE: The indicators chosen to monitor the consumption of linezolid were the DDD per 1,000 inhabitants per day, which enabled a comparison to be made between hospitals from 2004 to 2012, and of the pertinence of its prescription by different departments. RESULTS: From 2009 to 2013, 239 patients were evaluated through three 3-month stages. Prescriptions were for off-label use in 45 % of cases. Prescriptions were considered appropriate in 60 % of cases. Unsuitable treatment was either modified or discontinued (62 and 38 % of cases, respectively). Mean duration of linezolid treatment was 8 days, i.e. below the national mean duration reported in the literature. To highlight the impact of action taken by the team, a consensual strategy to treat ventilator-acquired pneumonia was elaborated with principal prescribers. Throughout the study, the mean DDD per 1,000 inhabitants per day increased very slowly and was lower than the eleven other French hospitals, which were secondarily included in this study. CONCLUSION: The multidisciplinary approach that was adopted for therapeutic education and delivery control led to an improvement in the proper use of linezolid. Similar strategy should be extended to other antimicrobial agents, such as carbapenems, for which both cost and risk of resistance emergence are of major concern. PMID- 25135807 TI - Intraocular pressure effects of common topical steroids for post-cataract inflammation: are they all the same? AB - The efficacy of topical corticosteroids as ocular anti-inflammatory agents following cataract surgery is well-documented. They also help to prevent a number of complications associated with post-operative ocular inflammation, including corneal edema and cystoid macular edema. However, topical corticosteroids are associated with side effects, such as increased intraocular pressure (IOP). Indeed, corticosteroid-induced ocular hypertension and the potential for steroid induced glaucoma remain the leading drawbacks of topical corticosteroid therapy. Some individuals are known to experience a high degree of IOP elevation with low doses or short durations of treatment with topical corticosteroids. Careful monitoring of IOP in such individuals is essential. Few randomized, controlled studies are available on the comparative safety and efficacy of common topical corticosteroids in the treatment of post-operative ocular inflammation. Furthermore, the lack of consistent reporting criteria for clinically significant IOP increases across clinical studies makes meaningful comparisons among corticosteroids difficult. This review aims to examine data from available published studies, including studies in steroid responders, to determine whether topical corticosteroids are the same in terms of their effect on IOP. Early generation corticosteroids, such as dexamethasone and prednisolone, are more likely to result in clinically significant increases in IOP. Newer corticosteroids, such as rimexolone and the retro-metabolically designed corticosteroid, loteprednol etabonate, offer similar anti-inflammatory efficacy to older corticosteroids with less effect on IOP. However, randomized controlled trials of newer corticosteroids are needed. The proportion of patients exhibiting an increase of >=10 mmHg IOP in clinical studies has emerged as the most clinically relevant parameter for ophthalmologists to consider when deciding on which topical corticosteroid to use. PMID- 25135808 TI - Management of vernal keratoconjunctivitis. AB - Vernal keratoconjunctivitis (VKC) is a relatively rare, chronic form of ocular allergy that can potentially cause severe visual complications. Affecting mainly children and young adults, it is an IgE- and T cell-mediated disease, leading to a chronic inflammation in which eosinophil, lymphocyte and structural cell activation are involved. Treatment of VKC requires a multiple approach that includes conservative measures and pharmacologic treatment. Patients and parents should be made aware of the long duration of disease, its chronic evolution and possible complications. Treatment should be based on the duration and frequency of symptoms and the severity of corneal involvement. Mast cell stabilizers and antihistamines have been proven to be effective for the treatment of mild to moderate forms of VKC. In the most severe cases, topical steroids can be used as rescue medication to reduce conjunctival and corneal inflammation. Immunomodulators that have been investigated for VKC treatment include topical ocular preparations of cyclosporine A and tacrolimus. Topical cyclosporine A has been proven to be effective in the long-term treatment of VKC, significantly improving signs and symptoms without significant side effects. PMID- 25135809 TI - Aflibercept for the treatment of age-related macular degeneration. AB - Aflibercept is a novel, recombinant, fusion protein that consists of portions of vascular endothelial growth factor (VEGF) receptor (R) 1 and VEGFR2 extracellular domains fused to the Fc portion of human immunoglobulin G1. It exhibits higher affinity for VEGF-A/-B and binds all the VEGF isoforms (VEGF-B and -C, placental growth factor). The efficacy of aflibercept was assessed in two randomized, double-masked, multicenter, active-controlled, clinical trials in patients with choroidal neovascularization due to exudative age-related macular degeneration (AMD) and compared it's efficacy to ranibizumab, which is already Food and Drug Administration (FDA)-approved for patients with wet AMD. In the two trials known as VIEW 1 and VIEW 2, aflibercept was as effective when dosed as 2 mg every 8 weeks after 3 monthly loading doses compared to monthly ranibizumab. Aflibercept was well tolerated with very rare systemic adverse events, including arterial thromboembolic events (ATEs). The incidence of ATEs was 1.8% during the first year of the clinical trials and included non-fatal strokes, non-fatal myocardial infarction, or death from vascular events or an unknown cause. In November 2011, aflibercept received FDA approval and is currently used in clinical practice for patients with wet AMD. PMID- 25135810 TI - Necrotizing scleritis and peripheral ulcerative keratitis associated with Wegener's granulomatosis. AB - INTRODUCTION: To evaluate the complications, efficacy of medical and surgical treatment, and outcome in patients with necrotizing scleritis and peripheral ulcerative keratitis associated with Wegener's granulomatosis. METHODS: The authors reviewed a series of seven patients with Wegener's granulomatosis treated in the Corneal Department of Zhongshan Ophthalmic Center and the Department of Ophthalmology of Kashgar First People's Hospital. A detailed chart review was performed to determine demographic characteristics, ocular presentation, biopsy and laboratory testing results, treatment, and final outcome. RESULTS: Wegener's granulomatosis was indicated by ocular and/or systemic findings; biopsy and immunohistochemistry results supported the diagnosis. Patients with necrotizing scleritis and/or peripheral ulcerative keratitis received cytotoxic immunosuppressive therapy; this, in conjunction with surgical treatment, halted the relentlessly progressive inflammation and preserved the integrity of the globe in 78% of eyes. Best-Corrected Visual Acuity remained stable in four of nine eyes, was improved in two of nine eyes, and decreased in three of nine eyes (secondary to cataract and/or stromal scarring). Although one patient died, treatment with corticosteroids and cytotoxic agents dramatically improved outcomes in these patients. CONCLUSION: Necrotizing scleritis and peripheral ulcerative keratitis often have a poor visual outcome, and may herald an underlying systemic vasculitis. Wegener's granulomatosis, with the associated necrotizing scleritis and peripheral ulcerative keratitis, should be managed with aggressive immunosuppression to avoid the associated morbidity and mortality. Thus, the ophthalmologist may play a significant role in its early diagnosis and treatment. PMID- 25135811 TI - Effect of topical loteprednol on intraocular pressure after selective laser trabeculoplasty for open-angle glaucoma. AB - INTRODUCTION: To determine whether there is a statistically significant difference in the decrease in intraocular pressure (IOP) after selective laser trabeculoplasty (SLT) between patients receiving a 5-7 days co-administration of loteprednol versus no loteprednol over the course of 1 year. METHODS: We conducted a retrospective chart review to evaluate use of loteprednol in patients aged 30-85 years undergoing SLT for open-angle glaucoma at our center over a 3 year period. RESULTS: Three hundred and eighteen eyes from 313 patients who underwent a 360 degrees SLT treatment between January 2008 and August 2011 were included in the analysis. Patients who received loteprednol showed a mean reduction of 2.5 (+/-SE 0.3) mmHg or 11.8% (+/-1.5%) in IOP versus a mean reduction of 3.2 (+/-0.6) mmHg or 14.9% (+/-2.5%) in those not treated with loteprednol. This difference showed a trend toward lower IOP without loteprednol, but this was not statistically significant (p = 0.29). CONCLUSION: Postoperative use of loteprednol does not appear to significantly affect IOP in patients undergoing SLT. A randomized double-blinded study in a larger group of patients would be required to clarify this issue. Until such information is available, we recommend that individual clinical judgment be used regarding whether to use topical steroids in patients undergoing SLT. PMID- 25135812 TI - Behavior of intraocular pressure after intravitreal injection of triamcinolone acetonide among egyptians. AB - PURPOSE: To evaluate the changes in intraocular pressure (IOP) after intravitreal injection of triamcinolone acetonide for the management of diabetic macular edema (DME). METHODS: The study design is a prospective, interventional, two-arm, dose response study. Nineteen patients with bilateral DME were included, one eye for every patient underwent intravitreal injection of 4 mg triamcinolone acetonide (group A, 19 eyes), and the other eye of the same patient underwent intravitreal injection of 8 mg triamcinolone acetonide (group B, 19 eyes); the selection as to which eye was to receive either dose was random. The patients were followed up for 6 months after injection; complete ophthalmological examination and optical coherent topography were done. RESULTS: Intravitreal triamcinolone acetonide was effective in reduction of DME in group A in the first 3 months only, while in group B with high dose (8 mg) the improvement continued for 6 months after injection. Significant IOP rise was observed in both groups with an incidence of 68.1% and 73.7% in groups A and B, respectively. IOP-lowering drugs were used to control IOP; however, one patient in each group needed glaucoma filtration surgery in both eyes after intractable glaucoma with failure of medical treatment. CONCLUSION: Although intravitreal injection of triamcinolone acetonide is very effective in managing DME and with lower cost than other modalities, the rise in IOP and the burden of glaucoma are major concerns. High corticosteroid responder is an individualized reaction irrespective of the intravitreal triamcinolone acetonide dose used. PMID- 25135813 TI - Metamemory monitoring and control following retrieval practice for text. AB - Test-taking is assumed to help learners diagnose what they do and do not know, and by so doing improve the effectiveness of their subsequent study. Previous work has examined metamemory monitoring (e.g., predictions of future performance) and control (e.g., restudy decisions) following testing or retrieval practice with relatively simple materials (e.g., word pairs). There is reason to believe, however, that such monitoring and control decisions might be more difficult with text materials, even after retrieval practice, owing perhaps to difficulty in accurately assessing one's performance on the retrieval-practice test. In two experiments, participants read texts about world regions, then engaged in retrieval practice or rereading of the information in those texts, made estimates about future performance, and then received an opportunity to restudy the texts before taking a final recall test, with self-paced restudy enabling an examination of control processes. Memory predictions were more accurate in the retrieval-practice than in the rereading condition, and learners in both conditions allocated restudy time on the basis of their predictions. Additionally, restudy provided a greater benefit following retrieval practice than following rereading. The present study has implications for how students can use retrieval practice with text to foster subsequent learning. PMID- 25135814 TI - A comparative study of an innate immune response in Lamprologine cichlid fishes. AB - Social interactions facilitate pathogen transmission and increase virulence. Therefore, species that live in social groups are predicted to suffer a higher pathogen burden, to invest more heavily in immune defence against pathogens, or both. However, there are few empirical tests of whether social species indeed invest more heavily in immune defence than non-social species. In the current study, we conducted a phylogenetically controlled comparison of innate immune response in Lamprologine cichlid fishes. We focused on three species of highly social cichlids that live in permanent groups and exhibit cooperative breeding (Julidochromis ornatus, Neolamprologus pulcher and Neolamprologus savoryi) and three species of non-social cichlids that exhibit neither grouping nor cooperative behaviour (Telmatochromis temporalis, Neolamprologus tetracanthus and Neolamprologus modestus). We quantified the innate immune response by injecting wild fishes with phytohaemagglutinin (PHA), a lectin that causes a cell-mediated immune response. We predicted that the three highly social species would show a greater immune reaction to the PHA treatment, indicating higher investment in immune defence against parasites relative to the three non-social species. We found significant species-level variation in immune response, but contrary to our prediction, this variation did not correspond to social system. However, we found that immune response was correlated with territory size across the six species. Our results indicate that the common assumption of a positive relationship between social system and investment in immune function may be overly simplistic. We suggest that factors such as rates of both in-group and out-group social interactions are likely to be important mediators of the relationship between sociality and immune function. PMID- 25135815 TI - Dual Ambulatory pH Monitoring in Patients with Gastroesophageal Reflux Rendered Asymptomatic with Proton Pump Inhibitor Therapy. AB - BACKGROUND: Studies have suggested that proton pump inhibitor (PPI) therapy in gastroesophageal reflux disease (GERD) achieves high rates of esophageal acid normalization. AIMS: Our aims were to investigate the adequacy of esophageal and gastric acid suppression in reflux patients rendered asymptomatic on optimized PPI therapy. METHODS: We retrospectively analyzed outcomes of dual-sensor, ambulatory 24-h pH monitoring in referred persistent reflux patients rendered asymptomatic on PPI therapy. After optimization, we analyzed esophageal and gastric pH profiles to assess acid suppression and examine differences between PPIs. In patients with repeat studies, comparisons between different PPI doses were made. RESULTS: Of 172 asymptomatic GERD patients, 75 (43.6 %) achieved symptomatic remission with once-daily dosing PPI, and 97 (56.4 %) patients required twice-daily dosing. Of the entire cohort, 93 (54.1 %) had abnormal and 79 (45.9 %) had normal esophageal pH profiles, with mean percent time pH < 4.0 of 14.3 and 2.4, respectively (p < 0.0001). The percent time esophageal pH was abnormal did not correlate with the percent time gastric pH was abnormal (p = 0.17). Different PPI formulations demonstrated differences in gastric--not esophageal--pH times, with esomeprazole exhibiting superior gastric pH suppression (p < 0.0001). Overall, gastric pH control remained suboptimal, with pH < 4.0 ranging between 30 and 50 %. Among patients with sequential pH studies, those with higher PPI dose had improved esophageal pH profiles (p < 0.01). CONCLUSIONS: In GERD patients rendered asymptomatic on PPI therapy, most continue to experience abnormal esophageal and gastric acid exposure. The efficacy of acid suppression therapy, in certain patients, may be much lower than previously thought. PMID- 25135816 TI - Microbial associates of the vine mealybug Planococcus ficus (Hemiptera: Pseudococcidae) under different rearing conditions. AB - Sap-feeding insects harbor diverse microbial endosymbionts that play important roles in host ecology and evolution, including contributing to host pest status. The vine mealybug, Planococcus ficus, is a serious pest of grapevines, vectoring a number of pathogenic grape viruses. Previous studies have shown that virus transmission is abolished when mealybugs are raised in the laboratory on potato. To examine the possible role of microbial symbionts in virus transmission, the archaeal, bacterial, and fungal microbiota of field and laboratory P. ficus were characterized using molecular and classical microbiological methods. Lab and field colonies of P. ficus harbored different microbiota. While both were dominated by the bacterial obligate nutritional symbionts Moranella and Tremblaya, field samples also harbored a third bacterium that was allied with cluster L, a lineage of bacterial symbionts previously identified in aphids. Archaea were not found in any of the samples. Fungal communities in field collected mealybugs were dominated by Metschnikowia and Cladosporium species, while those from laboratory-reared mealybugs were dominated by Alternaria and Cladosporium species. In conclusion, this study has identified a diverse set of microbes, most of which appear to be facultatively associated with P. ficus, depending on environmental conditions. The role of various members of the mealybug microbiome, as well as how the host plant affects microbial community structure, remains to be determined. PMID- 25135817 TI - A combined approach to assess the microbial contamination of the archimedes palimpsest. AB - A combined approach, using molecular and microscopic techniques, was used to identify the microbiota associated with the Archimedes Palimpsest, an unusual parchment manuscript. SEM analyses revealed the microbial damage to the collagen fibers and the presence of characteristic cell chains typical of filamentous bacteria and fungal spores. Molecular analysis confirmed a homogeneous bacterial community colonizing the manuscript. The phyla Proteobacteria and Actinobacteria were associated with this ancient parchment; the sequences were most related to uncultured clones detected in the human skin microbiome and in ephitelium, and to cultivated species of the genera Acinetobacter and Nocardiopsis. Nevertheless, a great variation was observed among the different sampled areas indicating fungal diversity. Blumeria spp. dominated in the healthy areas of the parchment while degraded areas showed disparate fungal communities, with dominant members of the genera Mucor and Cladosporium. In addition, the quantification of the beta-actin gene by real-time PCR analyses (qPCR) revealed a higher fungal abundance on degraded areas than on the healthy ones. PMID- 25135819 TI - A Licensed Combined Haemophilus influenzae Type b-Serogroups C and Y Meningococcal Conjugate Vaccine. AB - The highest incidence of meningococcal disease occurs in infants younger than 1 year of age. However, in the US, prior to June 2012, there was no meningococcal vaccine licensed for use in this age group. In the US, where both serogroups C and Y contribute substantially to the overall epidemiology of invasive meningococcal disease, a vaccine combining these capsular polysaccharides was developed. We review the newly licensed HibMenCY-TT (MenHibrixTM, GlaxoSmithKline Biologicals, Rixensart, Belgium), a novel vaccine containing Haemophilus influenzae type b (Hib) and serogroups C and Y Neisseria meningitidis conjugated to tetanus toxoid. We describe the vaccine, summarize the clinical trial data, and describe the patient populations recommended to receive HibMenCY-TT as their primary vaccination against Hib. Phase II and III clinical trials found HibMenCY TT to be well tolerated, safe, and immunogenic when administered at 2, 4, 6, and 12-15 months of age for primary vaccination against both Hib and serogroups C and Y meningococcal disease. In October 2012, the Advisory Committee on Immunisation Practice in the US recommended HibMenCY-TT vaccination for infants at increased risk of meningococcal disease. HibMenCY-TT may be given concomitantly with other routine infant vaccines. It induces antibodies against Hib as well as bactericidal activity against meningococcal serogroup C and Y without increasing the number of injections required. As meningococcal disease epidemiology is dynamic, global surveillance remains essential. In the future, other countries may also benefit from the addition of HibMenCY-TT into their vaccine armamentarium against meningococcal disease. PMID- 25135820 TI - Cold-adapted proteases as an emerging class of therapeutics. AB - Proteases have been used in medicine for several decades and are an established and well tolerated class of therapeutic agent. These proteases were sourced from mammals or bacteria that exist or have adapted to moderate temperatures (mesophilic organisms); however, proteases derived from organisms from cold environments-cold-adapted or psychrophilic proteases-generally have high specific activity, low substrate affinity, and high catalytic rates at low and moderate temperatures. Made possible by greater flexibility, psychrophilic enzymes interact with and transform the substrate at lower energy costs. Cold-adapted proteases have been used in a wide range of applications, including industrial functions, textiles, cleaning/hygiene products, molecular biology, environmental bioremediations, consumer food products, cosmetics, and pharmaceutical production. In addition to these applications, they have also shown promise as therapeutic modalities for cosmeceutical applications (by reducing glabellar [frown] lines) and a number of disease conditions, including bacterial infections (by disrupting biofilms to prevent bacterial infection), topical wound management (when used as a debridement agent to remove necrotic tissue and fibrin clots), oral/dental health management (by removing plaque and preventing periodontal disease), and in viral infections (by reducing the infectivity of viruses, such as human rhinovirus 16 and herpes simplex virus). Psychrophilic proteases with greater activity and stability (than the original organism-derived variant) have been developed; this coupled with available manufacturing recombinant production techniques suggests that cold-adapted proteases have a promising future as a distinct therapeutic class with diverse clinical applications. PMID- 25135818 TI - Surgical patients travel longer distances than non-surgical patients to receive care at a rural hospital in Mozambique. AB - BACKGROUND: Surgical care is increasingly recognised as an important component of global health delivery. However, there are still major gaps in knowledge related to access to surgical care in low-income countries. In this study, we compare distances travelled by surgical patients with patients seeking other medical services at a first-level hospital in rural Mozambique. METHODS: Data were collected on all inpatients at Hospital Rural de Chokwe in rural Mozambique between 20 June 2012 and 3 August 2012. Euclidean distances travelled by surgical versus non-surgical patients using coordinates of each patient's city of residence were compared. Data were analysed using ArcGIS 10 and STATA. RESULTS: In total, 500 patients were included. Almost one-half (47.6%) lived in the city where the hospital is based. By hospital ward, the majority (62.0%) of maternity patients came from within the hospital's city compared with only 35.2% of surgical patients. The average distance travelled was longest for surgical patients (42 km) compared with an average of 17 km for patients on all other wards. CONCLUSIONS: Patients seeking surgical care at this first-level hospital travel farther than patients seeking other services. While other patients may have access to at community clinics, surgical patients depend more heavily on the services available at first-level hospitals. PMID- 25135821 TI - Low specificity of a malaria rapid diagnostic test during an integrated community case management trial. AB - INTRODUCTION: Parasitological confirmation before administration of antimalarial treatment has been recommended by the World Health Organization in everyone presenting with symptoms suggestive of malaria at all levels of the health system. METHODS: The authors assessed the performance of a histidine-rich protein 2-based malaria rapid diagnostic test used by community health workers in the context of an integrated approach to diagnosis and treatment for malaria and pneumonia. A total of 525 children below 5 years of age were recruited into the study. Children with fever/history of fever within the last 24 h were tested with the rapid diagnostic test (RDT) and a blood smear was obtained for delayed reading. RESULTS: Overall, the FirstSignTM Malaria Pf (Unimed International Inc, South San Francisco, USA) has shown a high sensitivity profile of 97.9% (95% CI 96.3-98.8), but a low specificity of 53.4% (95% CI 49.1-57.7). The specificity was significantly lower during the high transmission season at 25.4% (95% CI 20.5 31.0) compared to 63.7% (95% CI 57.6-69.4%) at the low transmission season. The negative predictive value (NPV) was 95.4% (95% CI 93.2-96.9) and positive predictive value was 71.7% (95% CI 67.7-75.4). The NPV was significantly higher during the low transmission season at 98.2% (95% CI 95.7-99.3) than compared to 80.0% (95% CI 74.7-84.4) at the high transmission season. CONCLUSION: With such a low specificity, caution should be exercised when using these RDTs for community case management of malaria. PMID- 25135822 TI - Incidence and predisposing factors of vancomycin-induced nephrotoxicity in children. AB - INTRODUCTION: To investigate the pattern of vancomycin-associated nephrotoxicity in children and to examine potential predisposing factors for nephrotoxicity, including average serum trough concentrations >=10 MUg/mL. METHODS: Patients >=1 week old to <=15 years with normal baseline serum creatinine values who received vancomycin for >=48 h between October 2010 and September 2012 were retrospectively evaluated. Nephrotoxicity was defined as a serum creatinine increase of >=0.5 mg/dL or >=50% baseline increase over 2 days. Patients with average serum trough concentrations >=10 MUg/mL were compared with a lower trough group. RESULTS: Renal toxicity occurred in 72 (27.2%) of the 265 studied pediatric cases. High trough vancomycin levels >=10 MUg/mL were presented in 59 pediatric patients suffering from nephrotoxicity. Using multiple regression analysis, cases admitted to the intensive care unit (ICU) and to whom aminoglycoside medication was administered concurrently with vancomycin medication showed a significant high renal toxicity incidence [odds ratio (OR) 2.91; 95% confidence interval (CI) 1.70, 8.61; P value <0.03)] and (OR 9.11; 95% CI 4.11, 24.13; P < 0.05), respectively. CONCLUSION: Renal function tests and continuous monitoring of vancomycin trough levels for children receiving vancomycin therapy, especially admitted to the ICU and given other aminoglycoside medications, are essential. PMID- 25135823 TI - Treatment of Asymptomatic Carriers of Plasmodium falciparum with Artemether Lumefantrine: Impact on the Prevalence of Anemia. AB - INTRODUCTION: An investigation of whether treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine (AL), in addition to the routine treatment of symptomatic cases with AL, could improve the prevalence of anemia in 18 villages in Burkina Faso. METHODS: This was a single-center, controlled, parallel, cluster-randomized study to evaluate the effect of systematic treatment of P. falciparum asymptomatic carriers at a community level on hemoglobin (Hb) levels and anemic status of children (<5 years) and adults during four screening campaigns carried out over a 12-month period, compared with no treatment of asymptomatic carriers. RESULTS: The change in Hb level in all asymptomatic carriers aged >6 months from Day 1 to Day 28 of the first campaign was +0.53 g/dl (from 11.81 to 12.33 g/dl) in the intervention arm vs. -0.21 g/dl (from 12.06 to 11.86 g/dl) in the control arm (P < 0.001). During the same period, the proportion of asymptomatic carriers aged >6 months to <5 years with anemia in the intervention arm decreased by 31.1% (from 75.7% to 44.6%), compared with a decrease of 4.7% (from 76.3% to 71.6%) in the control arm. Over 12 months, the proportion of asymptomatic carriers with anemia (mild, moderate, or severe) was reduced in both arms. CONCLUSION: Systematic screening and treatment of asymptomatic carriers of P. falciparum with AL at the community level can reduce the prevalence of anemia in children in the short term (28 days), although the effect was not maintained at 12 months. PMID- 25135824 TI - Psoriasis, anti-tumor necrosis factor therapy, and tuberculosis: report of three challenging cases and literature review. AB - INTRODUCTION: The era of biologic therapies has provided new options for the treatment of chronic plaque psoriasis. However, safety concerns have led to intensive screening and monitoring of patients receiving anti-tumor necrosis factor alpha (anti-TNF-alpha) agents. METHODS: The authors describe the cases of three patients with moderate to severe psoriasis treated with anti-TNF agents, with challenging diagnostic and treatment aspects regarding tuberculosis (TB) infection, a serious adverse event associated with this type of treatment. The cases are discussed in the context of a comprehensive literature review describing the risk of TB associated with the use of TNF inhibitors. A critical review of the clinical trials that have tested the safety of these agents is also presented. RESULTS: One patient, who tested negatively for latent TB infection (LTBI) during screening, developed active TB under adalimumab therapy. For two other patients the diagnosis and management of LTBI in relation to anti-TNF therapy represented a challenge. Although clinical trials involving the use of anti-TNF therapy for psoriasis haven't demonstrated a high TB incidence, active TB is continuously reported in association with this treatment. CONCLUSIONS: Findings from clinical practice and the scientific literature indicate that anti TNF therapies are associated with an increased risk of TB, and close monitoring of patients is needed. PMID- 25135826 TI - A systematic review and meta-analysis on the role of varicosity treatment in the context of truncal vein ablation. AB - BACKGROUND: With the advent of endovenous truncal ablation under local anaesthetic for the treatment of varicose veins, the fate of varicosed tributaries has become controversial, with centres offering different timings of treatment, if offered at all. This study aims to review the literature assessing delayed and simultaneous varicosity treatment during truncal ablation. METHODS: Randomised trials and cohort studies concerning varicosity treatment timing were identified through a systematic literature search. Requirements for further treatment, quality of life and rate of venous thrombotic events were assessed for meta-analysis. RESULTS: Four studies were identified assessing need for further varicosity procedure, with no significant difference seen between simultaneous or delayed treatment (p = 0.339). Two studies assessed quality of life, with simultaneous treatment providing significantly improved outcomes at six weeks (p = 0.029) but not at 12 weeks (p = 0.283). Studies examining venous thrombotic events showed no difference in venous thromboembolism rate between simultaneous or delayed treatment approaches (p = 0.078). CONCLUSION: The evidence base regarding timing of varicosity treatment is sparse; however, it does show that simultaneous treatment of varicosities leads to early gains in quality of life, with a non-significant trend for fewer further procedures but more venous thrombotic events. PMID- 25135825 TI - Postoperative pyoderma gangrenosum in association with renal cell carcinoma and chronic lymphocytic leukemia. AB - INTRODUCTION: Pyoderma gangrenosum (PG) is a rare sterile neutrophilic dermatosis characterized by painful recurrent ulcerations. It is frequently associated with inflammatory bowel disease, rheumatoid arthritis, or malignancies. PG is a diagnosis of exclusion, and it is based on clinical presentation, histology, history of an underlying disease, and exclusion of other causes of ulceration. CASE REPORT: The authors report a 62-year-old male who developed a nonhealing ulcer at the site of incision following nephrectomy for renal cell carcinoma. Past medical history included chronic lymphocytic leukemia treated with rituximab. Histology of the skin lesion showed a phlegmonous nonspecific inflammation without being able to differentiate between a necrotizing wound infection and PG. The patient's condition was initially diagnosed as an infectious process and treated accordingly. After unsuccessful results with systemic antibiotics, high-dose corticosteroids induced prompt healing of the wound. On these bases, the diagnosis of postoperative PG within chronic lymphocytic leukemia and renal cell carcinoma was made. CONCLUSION: Faced with postoperative necrotizing ulceration resistant to correctly administered antibiotics, PG must be considered. In such condition, the diagnosis must not be guided primarily by histology and early advice of a dermatologist is recommended. PMID- 25135827 TI - Needle track tumor seeding after radiofrequency ablation of a thyroid tumor. AB - A 19-year-old female underwent two radiofrequency ablation procedures for a thyroid tumor that was proven to be nodular hyperplasia versus a follicular neoplasm by fine-needle aspiration. Two years after the last follow-up, the thyroid mass had grown and a newly developed mass was detected in the platysma muscle. After surgery, the thyroid mass was revealed to be a solid papillary thyroid carcinoma, and the subplatysmal mass was tumor seeding. PMID- 25135828 TI - CD1d(hi)CD5+ B cells expanded by GM-CSF in vivo suppress experimental autoimmune myasthenia gravis. AB - IL-10-competent subset within CD1d(hi)CD5(+) B cells, also known as B10 cells, has been shown to regulate autoimmune diseases. Whether B10 cells can prevent or suppress the development of experimental autoimmune myasthenia gravis (EAMG) has not been studied. In this study, we investigated whether low-dose GM-CSF, which suppresses EAMG, can expand B10 cells in vivo, and whether adoptive transfer of CD1d(hi)CD5(+) B cells would prevent or suppress EAMG. We found that treatment of EAMG mice with low-dose GM-CSF increased the proportion of CD1d(hi)CD5(+) B cells and B10 cells. In vitro coculture studies revealed that CD1d(hi)CD5(+) B cells altered T cell cytokine profile but did not directly inhibit T cell proliferation. In contrast, CD1d(hi)CD5(+) B cells inhibited B cell proliferation and its autoantibody production in an IL-10-dependent manner. Adoptive transfer of CD1d(hi)CD5(+) B cells to mice could prevent disease, as well as suppress EAMG after disease onset. This was associated with downregulation of mature dendritic cell markers and expansion of regulatory T cells resulting in the suppression of acetylcholine receptor-specific T cell and B cell responses. Thus, our data have provided significant insight into the mechanisms underlying the tolerogenic effects of B10 cells in EAMG. These observations suggest that in vivo or in vitro expansion of CD1d(hi)CD5(+) B cells or B10 cells may represent an effective strategy in the treatment of human myasthenia gravis. PMID- 25135829 TI - Single-cell analysis of innate cytokine responses to pattern recognition receptor stimulation in children across four continents. AB - Innate immunity instructs adaptive immunity, and suppression of innate immunity is associated with an increased risk for infection. We showed previously that whole-blood cellular components from a cohort of South African children secreted significantly lower levels of most cytokines following stimulation of pattern recognition receptors compared with whole blood from cohorts of Ecuadorian, Belgian, or Canadian children. To begin dissecting the responsible molecular mechanisms, we set out to identify the relevant cellular source of these differences. Across the four cohorts represented in our study, we identified significant variation in the cellular composition of whole blood; however, a significant reduction in the intracellular cytokine production on the single-cell level was only detected in South African children's monocytes, conventional dendritic cells, and plasmacytoid dendritic cells. We also uncovered a marked reduction in polyfunctionality for each of these cellular compartments in South African children compared with children from the other continents. Together, our data identify differences in cell composition, as well as profoundly lower functional responses of innate cells, in our cohort of South African children. A possible link between altered innate immunity and increased risk for infection or lower response to vaccines in South African infants needs to be explored. PMID- 25135830 TI - Identification of a novel neutrophil population: proangiogenic granulocytes in second-trimester human decidua. AB - The maternal leukocytes of the first-trimester decidua play a fundamental role in implantation and early development of the fetus and placenta, yet little is known regarding the second-trimester decidual environment. Our multicolor flow cytometric analyses of human decidual leukocytes detected an elevation in tissue resident neutrophils in the second trimester. These cells in both human and murine samples were spatially restricted to decidua basalis. In comparison with peripheral blood neutrophils (PMNs), the decidual neutrophils expressed high levels of neutrophil activation markers and the angiogenesis-related proteins: vascular endothelial growth factor-A, Arginase-1, and CCL2, similarly shown in tumor-associated neutrophils. Functional in vitro assays showed that second trimester human decidua conditioned medium stimulated transendothelial PMN invasion, upregulated VEGFA, ARG1, CCL2, and ICAM1 mRNA levels, and increased PMN driven in vitro angiogenesis in a CXCL8-dependent manner. This study identified a novel neutrophil population with a physiological, angiogenic role in human decidua. PMID- 25135831 TI - Pregnancy and malaria exposure are associated with changes in the B cell pool and in plasma eotaxin levels. AB - Pregnancy triggers immunological changes aimed to tolerate the fetus, but its impact on B lymphocytes is poorly understood. In addition, exposure to the Plasmodium parasite is associated with altered distribution of peripheral memory B cell (MBC) subsets. To study the combined impact of high malaria exposure and pregnancy in B cell subpopulations, we analyzed PBMCs from pregnant and nonpregnant individuals from a malaria-nonendemic country (Spain) and from a high malaria-endemic country (Papua New Guinea). In the malaria-naive cohorts, pregnancy was associated with a significant expansion of all switched (IgD(-)) MBC and a decrease of naive B cells. Malaria-exposed women had more atypical MBC and fewer marginal zone-like MBC, and their levels correlated with both Plasmodium vivax- and Plasmodium falciparum-specific plasma IgG levels. Classical but not atypical MBC were increased in P. falciparum infections. Moreover, active atypical MBC positively correlated with proinflammatory cytokine plasma concentrations and had lower surface IgG levels than the average. Decreased plasma eotaxin (CCL11) levels were associated with pregnancy and malaria exposure and also correlated with B cell subset frequencies. Additionally, active atypical and active classical MBC expressed higher levels of eotaxin receptor CCR3 than the other B cell subsets, suggesting a chemotactic effect of eotaxin on these B cell subsets. These findings are important to understand immunity to infections like malaria that result in negative outcomes for both the mother and the newborn and may have important implications on vaccine development. PMID- 25135832 TI - Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry. AB - We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Deltanef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV 1. PMID- 25135834 TI - Bispecificity for myelin and neuronal self-antigens is a common feature of CD4 T cells in C57BL/6 mice. AB - The recognition of multiple ligands by a single TCR is an intrinsic feature of T cell biology, with important consequences for physiological and pathological processes. Polyspecific T cells targeting distinct self-antigens have been identified in healthy individuals as well as in the context of autoimmunity. We have previously shown that the 2D2 TCR recognizes the myelin oligodendrocyte glycoprotein epitope (MOG)35-55 as well as an epitope within the axonal protein neurofilament medium (NF-M15-35) in H-2(b) mice. In this study, we assess whether this cross-reactivity is a common feature of the MOG35-55-specific T cell response. To this end, we analyzed the CD4 T cell response of MOG35-55-immunized C57BL/6 mice for cross-reactivity with NF-M15-35. Using Ag recall responses, we established that an important proportion of MOG35-55-specific CD4 T cells also responded to NF-M15-35 in all mice tested. To study the clonality of this response, we analyzed 22 MOG35-55-specific T cell hybridomas expressing distinct TCR. Seven hybridomas were found to cross-react with NF-M15-35. Using an alanine scan of NF-M18-30 and an in silico predictive model, we dissected the molecular basis of cross-reactivity between MOG35-55 and NF-M15-35. We established that NF M F24, R26, and V27 proved important TCR contacts. Strikingly, the identified TCR contacts are conserved within MOG38-50. Our data indicate that due to linear sequence homology, part of the MOG35-55-specific T cell repertoire of all C57BL/6 mice also recognizes NF-M15-35, with potential implications for CNS autoimmunity. PMID- 25135833 TI - SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. AB - Coronaviruses (CoV) have recently emerged as potentially serious pathogens that can cause significant human morbidity and death. The severe acute respiratory syndrome (SARS)-CoV was identified as the etiologic agent of the 2002-2003 international SARS outbreak. Yet, how SARS evades innate immune responses to cause human disease remains poorly understood. In this study, we show that a protein encoded by SARS-CoV designated as open reading frame-9b (ORF-9b) localizes to mitochondria and causes mitochondrial elongation by triggering ubiquitination and proteasomal degradation of dynamin-like protein 1, a host protein involved in mitochondrial fission. Also, acting on mitochondria, ORF-9b targets the mitochondrial-associated adaptor molecule MAVS signalosome by usurping PCBP2 and the HECT domain E3 ligase AIP4 to trigger the degradation of MAVS, TRAF3, and TRAF 6. This severely limits host cell IFN responses. Reducing either PCBP2 or AIP4 expression substantially reversed the ORF-9b-mediated reduction of MAVS and the suppression of antiviral transcriptional responses. Finally, transient ORF-9b expression led to a strong induction of autophagy in cells. The induction of autophagy depended upon ATG5, a critical autophagy regulator, but the inhibition of MAVS signaling did not. These results indicate that SARS-CoV ORF-9b manipulates host cell mitochondria and mitochondrial function to help evade host innate immunity. This study has uncovered an important clue to the pathogenesis of SARS-CoV infection and illustrates the havoc that a small ORF can cause in cells. PMID- 25135835 TI - Composition and occurrence of lipid droplets in the cyanobacterium Nostoc punctiforme. AB - Inclusions of neutral lipids termed lipid droplets (LDs) located throughout the cell were identified in the cyanobacterium Nostoc punctiforme by staining with lipophylic fluorescent dyes. LDs increased in number upon entry into stationary phase and addition of exogenous fructose indicating a role for carbon storage, whereas high-light stress did not increase LD numbers. LD accumulation increased when nitrate was used as the nitrogen source during exponential growth as compared to added ammonia or nitrogen-fixing conditions. Analysis of isolated LDs revealed enrichment of triacylglycerol (TAG), alpha-tocopherol, and C17 alkanes. LD TAG from exponential phase growth contained mainly saturated C16 and C18 fatty acids, whereas stationary phase LD TAG had additional unsaturated fatty acids characteristic of whole cells. This is the first characterization of cyanobacterial LD composition and conditions leading to their production. Based upon their abnormally large size and atypical location, these structures represent a novel sub-organelle in cyanobacteria. PMID- 25135836 TI - Repeat analysis and incurred sample reanalysis: recommendation for best practices and harmonization from the global bioanalysis consortium harmonization team. AB - The A7 harmonization team (A7 HT), a part of the Global Bioanalysis Consortium (GBC), focused on reviewing best practices for repeat analysis and incurred sample reanalysis (ISR) as applied during regulated bioanalysis. With international representation from Europe, Latin America, North America, and the Asia Pacific region, the team first collated common practices and guidance recommendations and assessed their suitability from both a scientific and logistical perspective. Subsequently, team members developed best practice recommendations and refined them through discussions and presentations with industry experts at scientific meetings. This review summarizes the team findings and best practice recommendations. The few topics where no consensus could be reached are also discussed. The A7 HT recommendations, together with those from the other GBC teams, provide the basis for future international harmonization of regulated bioanalytical practices. PMID- 25135837 TI - Population pharmacokinetic/pharmacodynamic modeling of guanfacine effects on QTc and heart rate in pediatric patients. AB - Using a previously developed population pharmacokinetic model, an exposure response (ER) model was successfully developed to describe guanfacine plasma concentrations and changes in heart rate (HR) and the QT interval. Guanfacine exposure was associated with small decreases in HR and a small prolongation of the population-corrected QT (QTcP) interval. Based on the final ER model for effect of guanfacine on HR, the estimated population typical decrease in HR would be 2.3% (2.1-2.7%) of the baseline circadian HR for every 1 ng/mL of guanfacine exposure. A QTcP was developed for the analysis using the sampled population. An effect of sex on baseline-corrected QT (BQTP) was the only covariate effect in the final ER model for QTcP, its inclusion resulting in a typical baseline QTcP estimate that is 9 (5-13) ms higher for females. There was no evidence of QT-RR hysteresis. A linear model was used to relate guanfacine plasma concentrations to QTcP. The typical (95% confidence interval) slope parameter was estimated to be 0.941 (0.62-1.25) ms/ng/mL. The final model predicted an approximate 1-ms increase from baseline for every 1 ng/mL of guanfacine in plasma. The main predictor of QTcP prolongation was guanfacine exposure, which decreased with body weight and increased with dose. PMID- 25135838 TI - Organ transplantation from donors (cadaveric or living) with a history of malignancy: review of the literature. AB - The evolution of organ transplantation has resulted in extended lifespan as well as better life quality of patients with end-stage diseases, which in turn causes an increased demand for organs. The persistent organ shortage requires a careful reconsideration of potential donors (living or cadaveric) that have current or historical malignancies. Donors with low-grade skin tumors, carcinomas in situ of the uterine cervix, and primary central nervous system (CNS) tumors can be considered as potential donors for recipients dying on wait list longing for organ transplantation. Recently, transplant centers have turned to other types of malignancies including low grade renal cell carcinoma, prostate, ureteral, endometrial and breast cancer, and favorable outcomes have been shown in such innovations. When considering donors with a history of malignancy, general biologic behavior of the tumor type, histology and stage at the time of diagnosis, and the length of disease-free interval should be considered (Transplantation 2002;74(12):1657-1663). With the review of literatures, we illustrate the organ utilization from donors with malignancies all around the world since earlier times and give some suggestions for decision making under the circumstance of whether to choose those marginal donors or not on the basis of reviewed literatures. PMID- 25135839 TI - The Spanish version of the Body Image Scale (S-BIS): psychometric properties in a sample of breast and gynaecological cancer patients. AB - PURPOSE: The aim of this study is to develop a Spanish version of the Body Image Scale (Hopwood et al. Eur J Cancer 37(2):189-197, 2001) and to analyze its psychometric properties in a sample of women with breast or gynaecological cancer. METHODS: The Spanish version of the Body Image Scale was developed using a forward and backward translation technique. A total sample of 100 women who had undergone radical surgery for breast (n = 50) or gynaecological cancer (n = 50) completed the scale. RESULTS: Factor analysis resulted in a single-factor solution, both in the total sample and in the two subgroups, accounting for >76 % variance. Internal consistency (Cronbach's alpha) was 0.960. The Spanish version of the Body Image Scale correlated negatively with self-esteem (r = -0.733), quality of life (r = -0.632) and age (r = -0.643) and positively with depression (r = 0.832) and anxiety (r = 0.564); all p values < 0.01. CONCLUSIONS: To our knowledge, this is the first study that provides a Spanish version of the Body Image Scale. Our results show a stable factorial structure between samples with a single-factor solution and good psychometric properties, suggesting that it is a suitable tool for measuring body image concerns among Spanish-speaking cancer patients. Its brevity and comprehensibility allow a quick assessment both in clinical and research settings. PMID- 25135841 TI - The basolateral amygdala is necessary for negative prediction errors to enhance cue salience, but not to produce conditioned inhibition. AB - Behavioral evidence shows that prediction errors (PEs) not only drive associative learning, but also enhance the salience of predictive cues, making them better able to capture attention when they are next encountered. Research from our laboratory suggests that this latter consequence of PEs depends on a neural circuit that includes the amygdala. Lesions of the basolateral complex of the amygdala (BLA), for instance, selectively disrupt enhancements in cue processing that are normally induced by positive PEs without compromising simple excitatory learning. This result is consistent with electrophysiological evidence showing that BLA neurons track positive PEs. Interestingly, the same neurons also seem to track negative PEs, suggesting the possibility that the BLA might also use these errors to drive enhancements in cue processing. Here, we examined the role of the BLA in the processing (Experiment 1) and utilization (Experiment 2) of negative PEs in increasing cue salience in an unblocking procedure. Using FOS expression as an index of neural activity, Experiment 1 confirmed that BLA neurons track negative PEs with reinforcement downshifts. This tracking was evident both when these errors were generated by decreasing the concentration of a sucrose reinforcer (which encourages the development of conditioned inhibition) and when they were generated by decreasing the number of sucrose reinforcers (which encourages excitatory learning - unblocking - and allows the detection of enhancements in cue processing). Experiment 2 demonstrated that BLA lesions abolished enhancements in cue processing while sparing inhibitory learning. These results suggest a general role of the BLA in utilizing PEs, whatever their sign, for boosting cue processing. PMID- 25135840 TI - Glioblastoma multiforme from diagnosis to death: a prospective, hospital-based, cohort, pilot feasibility study of patient reported symptoms and needs. AB - PURPOSE: Glioblastoma (GBM) patients have many palliative care (PC) issues. To date, there are no studies examining the prospective usage of validated PC assessment tools as patient reported outcome measures for GBM patients. METHODS: GBM patients' PC issues were assessed from diagnosis to death or for at least 12 months every 7 weeks (+/-8 days) using semi-structured interviews and the Hospice and Palliative Care Evaluation (HOPE, including Eastern Cooperative Oncology Group (ECOG) performance status, 17 items) and the Palliative Outcome Scale (POS, 11 items). Data from patients who died within 12 months of the last patient's enrollment were evaluated using summarizing content analysis, visual graphical analysis (VGA), and linear mixed models for repeated measures. RESULTS: Nineteen of 33 patients screened were enrolled; two dropped out and four were still alive at the end of the study. The remaining 13 were assessed at 59 points until death (time range 4-68 weeks; 1-10 contacts per patient; assessment: self, 33; joint, 8; external, 18). VGA of the HOPE and POS data, including all 1,652 assessed item data, showed consistent trajectory profiles for 14 of 28 items: 10 were increasing (meaning symptom worsening) and comprised predominantly psychosocial issues and care dependency. Type of assessment partly interacted with time, however, not qualitatively so. Analysis of semi-structured interviews revealed delayed interactions with PC/hospice services and numerous neuropsychiatric problems not detected by HOPE and POS. CONCLUSIONS: Prospective self-assessment of GBM patients' PC issues is feasible. However, disease progression may necessitate further, external assessment. Modification of existing PC assessment tools is needed to detect GBM-specific issues. PMID- 25135843 TI - Randall Dudley Bloomfield, MD: physician and advocate for disadvantaged communities. PMID- 25135842 TI - Strategies for hepatitis C testing and linkage to care for vulnerable populations: point-of-care and standard HCV testing in a mobile medical clinic. AB - Despite new Hepatitis C virus (HCV) therapeutic advances, challenges remain for HCV testing and linking patients to care. A point-of-care (POC) HCV antibody testing strategy was compared to traditional serological testing to determine patient preferences for type of testing and linkage to treatment in an innovative mobile medical clinic (MMC). From 2012 to 2013, all 1,345 MMC clients in New Haven, CT underwent a routine health assessment, including for HCV. Based on patient preferences, clients could select between standard phlebotomy or POC HCV testing, with results available in approximately 1 week versus 20 min, respectively. Outcomes included: (1) accepting HCV testing; (2) preference for rapid POC HCV testing; and (3) linkage to HCV care. All clients with reactive test results were referred to a HCV specialty clinic. Among the 438 (32.6 %) clients accepting HCV testing, HCV prevalence was 6.2 % (N = 27), and 209 (47.7 %) preferred POC testing. Significant correlates of accepting HCV testing was lower for the "baby boomer" generation (AOR 0.67; 95 % CI 0.46-0.97) and white race (AOR 0.55; 95 % CI 0.36-0.78) and higher for having had a prior STI diagnosis (AOR 5.03; 95 % CI 1.76-14.26), prior injection drug use (AOR 2.21; 95 % CI 1.12-4.46), and being US-born (AOR 1.76; 95 % CI 1.25-2.46). Those diagnosed with HCV and preferring POC testing (N = 16) were significantly more likely than those choosing standard testing (N = 11) to be linked to HCV care within 30 days (93.8 vs. 18.2 %; p < 0.0001). HCV testing is feasible in MMCs. While patients equally preferred POC and standard HCV testing strategies, HCV-infected patients choosing POC testing were significantly more likely to be linked to HCV treatment. Important differences in risk and background were associated with type of HCV testing strategy selected. HCV testing strategies should be balanced based on costs, convenience, and ability to link to HCV treatment. PMID- 25135844 TI - Mortality from internal and external radiation exposure in a cohort of male German uranium millers, 1946-2008. AB - PURPOSE: To examine exposure-response relationships between ionizing radiation and several mortality outcomes in a subgroup of 4,054 men of the German uranium miner cohort study, who worked between 1946 and 1989 in milling facilities, but never underground or in open pit mines. METHODS: Mortality follow-up was from 1946 to 2008, accumulating 158,383 person-years at risk. Cumulative exposure to radon progeny in working level months (WLM) (mean = 8, max = 127), long-lived radionuclides from uranium ore dust in kBqh/m(3) (mean = 3.9, max = 132), external gamma radiation in mSv (mean = 26, max = 667) and silica dust was estimated by a comprehensive job-exposure matrix. Internal Poisson regression models were applied to estimate the linear excess relative risk (ERR) per unit of cumulative exposure. RESULTS: Overall, a total of 457, 717 and 111 deaths occurred from malignant cancer, cardiovascular diseases and non-malignant respiratory diseases, respectively. Uranium ore dust and silica dust were not associated with mortality from any of these disease groups. A statistically significant relationship between cumulative radon exposure and mortality from all cancers (ERR/100 WLM = 1.71; p = 0.02), primarily due to lung cancer (n = 159; ERR/100 WLM = 3.39; p = 0.05), was found. With respect to cumulative external gamma radiation, an excess of mortality of solid cancers (n = 434; ERR/Sv = 1.86; p = 0.06), primarily due to stomach cancer (n = 49, ERR/Sv = 10.0; p = 0.12), was present. CONCLUSION: The present findings show an excess mortality from lung cancer due to radon exposure and from solid cancers due to external gamma radiation in uranium millers that was not statistically significant. Exposure to uranium was not associated with any cause of death, but absorbed organ doses were estimated to be low. PMID- 25135845 TI - Impact of desmopressin on nocturia due to nocturnal polyuria in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). AB - PURPOSE: To evaluate the efficacy of desmopressin on nocturia, quality of sleep (QoS), and health-related quality of life (HRQoL) in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and nocturia due to nocturnal polyuria (NP) as the predominant symptom. METHODS: A German observational, multicenter, post-marketing surveillance study including men with LUTS/BPH and nocturia due to NP starting 3 months of desmopressin treatment. RESULTS: In total, 137 patients with a mean of 3.8 nocturnal voids (range 2-7) were included. Desmopressin significantly reduced the mean number of nocturnal voids by 53 %, mean IPSS nocturia question by 50 %, and the mean ratio of night/24-h urine volume by 39 % from baseline to endpoint. The hours of undisturbed sleep significantly increased by 74 %; 71 % of men reported about undisturbed sleep of >=4 h at study end. Additionally, there was a significant reduction in the Leeds Sleep Evaluation Questionnaire score, indicating a clinically relevant QoS improvement. This was associated with an improved HRQoL, as shown by a significant improvement in both the mean IPSS-QoL question by 43 % and mean ICIQ-N nocturia problem question by 53 %. Concomitant alpha-blocker use had no effect on the efficacy of desmopressin. The incidence of adverse events was low (2.2 %). Hyponatremia was not observed in any patient. The majority of patients and physicians rated the efficacy and tolerability of desmopressin as good/very good. CONCLUSIONS: Desmopressin is an effective and well-tolerated treatment for nocturia due to NP in patients with LUTS/BPH in daily practice under routine conditions. PMID- 25135847 TI - Race/ethnicity and disparities in mastectomy practice in the Breast Cancer Care in Chicago study. AB - PURPOSE: To examine racial/ethnic disparities in mastectomy practice and explore mediating factors to explain the disparity. METHODS: Participants included 989 females aged 30-79 years, from a population-based study of newly diagnosed (primary in situ/invasive) breast cancer patients, in Chicago, Illinois, from 2005 to 2008, who completed an interview. Medical records were also abstracted for tumor, diagnostic, and treatment information. Multivariable logistic regression models with model-based standardization were used to estimate risk differences. Differences in rescaled coefficients were used to estimate the proportion of the disparity that could be mediated by patient and tumor characteristics. RESULTS: Mastectomy prevalence overall was 40 %. Factors significantly associated with increased rates of mastectomy (p < 0.05) included the following: non-Hispanic (nH) black and Hispanic race/ethnicity; younger age at diagnosis; lower socioeconomic status (SES); lack of recency of and adherence to screening mammography; and higher tumor pathologic stage and grade. In adjusted models (age, body mass index, comorbidity), compared to nH white patients, mastectomy was increased by 10 % points in both nH black (95 % confidence interval [CI] 0.03, 0.18; p = 0.007) and Hispanic (95 % CI 0.01, 0.19; p = 0.028) patients. After accounting for the proportion of disparity mediated by tumor stage, the disparity was reduced by about a third in nH black (risk difference = 0.07, 95 % CI -0.01, 0.14) and half in Hispanic patients (risk difference = 0.04, 95 % CI -0.05, 0.13). Additional control for mediation by SES and other tumor-related factors almost completely eliminated the nH black:nH white disparity. CONCLUSIONS: The best approach to reducing the racial/ethnic disparity in mastectomy rates would be to intervene on factors that could affect stage at diagnosis. PMID- 25135846 TI - Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification. AB - A strategy for generating diverse collections of small molecules has been developed that features a multicomponent assembly process (MCAP) to efficiently construct a variety of intermediates possessing an aryl aminomethyl subunit. These key compounds are then transformed via selective ring-forming reactions into heterocyclic scaffolds, each of which possesses suitable functional handles for further derivatizations and palladium-catalyzed cross coupling reactions. The modular nature of this approach enables the facile construction of libraries of polycyclic compounds bearing a broad range of substituents and substitution patterns for biological evaluation. Screening of several compound libraries thus produced has revealed a large subset of compounds that exhibit a broad spectrum of medicinally-relevant activities. PMID- 25135848 TI - Impact of the Japanese gastric cancer screening system on treatment outcomes in gastric gastrointestinal stromal tumor (GIST): an analysis based on the GIST registry. AB - BACKGROUND: Gastrointestinal stromal tumors (GISTs) of the stomach are found incidentally during gastric cancer screening in Japan. This study investigated whether the Japanese gastric cancer screening system helps to improve treatment outcomes in gastric GIST based on an analysis of the GIST registry conducted by the Kinki GIST Study Group. METHODS: The registry was designed to collect data on background characteristics, treatment methods, pathologic characteristics, and prognosis of GIST from January 2003 through December 2007 at 40 participating institutions. RESULTS: The study enrolled 672 GIST patients, 482 of whom had gastric GIST. According to the modified National Institutes of Health consensus criteria, 22.6 % of the patients were classified as high risk for recurrence, 18.5 % as intermediate risk, 35.9 % as low risk, and 13.9 % as very low risk. After exclusion of the patients inevaluable for treatment outcome, the study included 137 symptomatic patients (symptomatic group) and 147 asymptomatic patients (asymptomatic group). The diagnosis of the asymptomatic patients was determined through gastric cancer screening. The median tumor size in the asymptomatic group was significantly smaller than in the symptomatic group (3.5 vs. 5.3 cm; P < 0.0001). The 5-year recurrence-free survival rate in the asymptomatic high-risk patients (72.4 %) was lower than in their symptomatic counterparts (46.3 %) (P = 0.017). More patients in the asymptomatic group underwent laparoscopic surgery (42.2 vs. 27.2 %; P = 0.0081). CONCLUSIONS: By identifying asymptomatic patients, the Japanese gastric cancer screening system contributes to early detection of gastric GIST and favorable treatment outcomes. PMID- 25135849 TI - Open versus endoscopic carpal tunnel release: a meta-analysis of randomized controlled trials. AB - BACKGROUND: Carpal tunnel syndrome is a common compressive neuropathy of the median nerve. The efficacy and safety of endoscopic versus open carpal tunnel release remain controversial. QUESTIONS/PURPOSES: The purpose of this study was to determine whether endoscopic compared with open carpal tunnel release provides better symptom relief, validated outcome scores, short- and long-term strength, and/or digital sensibility; entails a differential risk of complications such as nerve injury, scar tenderness, pillar pain, and reoperation; allows an earlier return to work; and takes less operative time. METHODS: The English-language literature was searched using MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials. Randomized controlled trials that compared endoscopic and open carpal tunnel release were included in the meta-analysis. Methodologic quality was assessed with the Consolidated Standards Of Reporting Trials (CONSORT) checklist, and a sensitivity analysis was performed. Symptom relief, Boston Carpal Tunnel Questionnaire (BCTQ) scores, strength, digital sensibility, complications, reoperation, interval to return to work, and operative time were analyzed. Twenty one randomized controlled trials containing 1859 hands were included. RESULTS: Endoscopically treated patients showed similar symptom relief and BCTQ scores; better early recovery of grip strength (mean difference [MD], 3.03 kg [0.08 5.98]; p = 0.04) and pinch strength (MD, 0.77 kg [0.33-1.22]; p < 0.001) but no advantage after 6 months; lower risk of scar tenderness (risk ratio [RR], 0.53 [0.35-0.82]; p = 0.005); higher risk of nerve injury (RR, 2.84 [1.08-7.46]; p = 0.03), most of which were transient neurapraxias. Similar risk of pillar pain and reoperation; an earlier return to work (MD, -8.73 days [-12.82 to -4.65]; p < 0.001); and reduced operative time (MD, -4.81 minutes [-9.23 to -0.39]; p = 0.03). CONCLUSIONS: High-level evidence from randomized controlled trials indicates that endoscopic release allows earlier return to work and improved strength during the early postoperative period. Results at 6 months or later are similar according to current data except that patients undergoing endoscopic release are at greater risk of nerve injury and lower risk of scar tenderness compared with open release. While endoscopic release may appeal to patients who require an early return to work and activities, surgeons should be cognizant of its elevated incidence of transient nerve injury amid its similar overall efficacy to open carpal tunnel release. Additional research is required to define the learning curve of endoscopic release and clarify the influence of surgeon volume on its safety. PMID- 25135850 TI - CORR Insights(r): a novel system improves preservation of osteochondral allografts. PMID- 25135851 TI - CORR Insights (r): Patient-specific anatomical and functional parameters provide new insights into the pathomechanism of cam FAI. PMID- 25135852 TI - CORR Insights: Is synovial C-reactive protein a useful marker for periprosthetic joint infection? PMID- 25135853 TI - Editorial comment: 2013 Limb Lengthening and Reconstruction Society. PMID- 25135854 TI - It is that time of year again ... immunization opportunities for older adults. PMID- 25135856 TI - Generation of antibodies against membrane proteins. AB - The monoclonal antibody has become an important therapeutic in the treatment of both hematological malignancies and solid tumors. The recent success of antibody drug conjugates (ADCs) has broadened the extent of the potential target molecules in cancer immunotherapy. As a result, even molecules of low abundance have become targets for cytotoxic reagents. The multi-pass membrane proteins are an emerging target for the next generation antibody therapeutics. One outstanding challenge is the difficulty in preparing a sufficient amount of these membrane proteins so as to be able to generate the functional antibody. We have pursued the expression of various membrane proteins on the baculovirus particle and the utilization of displayed protein for immunization. The strong antigenicity of the virus acts either as a friend or foe in the making of an efficient antibody against an immunologically tolerant antigen. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. PMID- 25135855 TI - Significance of redox-active cysteines in human FAD synthase isoform 2. AB - FAD synthase (FMN:ATP adenylyl transferase, FMNAT or FADS, EC 2.7.7.2) is the last enzyme in the pathway converting riboflavin into FAD. In humans, FADS is localized in different subcellular compartments and exists in different isoforms. Isoform 2 (490-amino acids) is organized in two domains: the 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reductase domain, that is the FAD-forming catalytic domain, and one resembling a molybdopterin-binding (MPTb) domain, with a hypothetical regulatory role. hFADS2 contains ten Cys residues, seven of which located in the PAPS reductase domain, with a possible involvement either in FAD synthesis or in FAD delivery to cognate apo-flavoproteins. A homology model of the PAPS reductase domain of hFADS2 revealed a co-ordinated network among the Cys residues in this domain. In this model, C312 and C303 are very close to the flavin substrate, consistent with a significantly lowered FAD synthesis rate in C303A and C312A mutants. FAD synthesis is also inhibited by thiol-blocking reagents, suggesting the involvement of free cysteines in the hFADS2 catalytic cycle. Mass spectrometry measurements and titration with thiol reagents on wt hFADS2 and on several individual cysteine/alanine mutants allowed us to detect two stably reduced cysteines (C139 and C241, one for each protein domain), two stable disulfide bridges (C399-C402, C303-C312, both in the PAPS domain), and two unstable disulfides (C39-C50; C440-C464). Whereas the C39-C50 unstable disulfide is located in the MPTb domain and appears to have no catalytic relevance, a cysteine-based redox switch may involve formation and breakdown of a disulfide between C440 and C464 in the PAPS domain. PMID- 25135857 TI - N-terminal region of human chemokine receptor CXCR3: Structural analysis of CXCR3(1-48) by experimental and computational studies. AB - Our study on the highly charged N-terminal peptide of the human chemokine receptor CXCR3 by spectroscopic methods in solution and by means of molecular dynamics simulations showed that the charge content modulates the intrinsic structural preference of its flexible backbone. Collectively, our findings suggest that the structural organization of a protein should be seen as a part of a continuum in which the ratio between electrostatic and hydrophobic interactions and the intrinsic flexibility are important properties used to optimize the folding. When this ratio changes and the structure is intrinsically flexible, the structural organization of the system moves along the continuum of the possible conformational states. By all this combined information, one can describe the structure of CXCR3(1-48) as an ensemble of conformations. In fact, the peptide shows stretches of negative charges embedded in a flexible sequence which can be used to maximize promiscuous interactions relevant to molecular recognition but globally the peptide appears as a poly-structured globule-like ensemble that is dynamically stabilized by H-bonds. We have approached the study of the most populated ensembles with subset selection to explain our experimental data also by evidencing that the changes into the fraction of charged residues discriminate between dynamically poly-structured states, conceivably because of small free energy barriers existing between the different conformations of CXCR3(1-48). Therefore, the overlap of a highly flexible backbone, negatively charged residues and sites which can be modified by post-translational modifications represent the structural organization that controls the molecular mechanisms underlying the biological functions carried out by CXCR3(1-48). PMID- 25135858 TI - Soluble epoxide hydrolase activity regulates inflammatory responses and seizure generation in two mouse models of temporal lobe epilepsy. AB - Neuroinflammation is known to be involved in epileptogenesis with unclear mechanisms. Inhibition of soluble epoxide hydrolase (sEH) seems to offer anti inflammatory protection to ischemic brain injury in rodents. Thus, it is hypothesized that sEH inhibition might also affect the neuroinflammatory responses caused by epileptic seizures. In the present study, we investigated the involvement of sEH in neuroinflammation, seizure generation and subsequent epileptogenesis using two mouse models of temporal lobe epilepsy. Experimental epileptic seizures were induced by either pilocarpine or electrical amygdala kindling in both wild-type (WT) C57BL/6 mice and sEH knockout (sEH KO) mice. The sEH expression in the hippocampus was detected by immunohistochemistry and Western blot analysis. The effects of the sEH hydrolase inhibitors, 12-(3 adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and N-[1-(1-oxopropyl)-4 piperidinyl]-N'-[4-(trifluoromethoxy) phenyl)-urea (TPPU), and of the genetic deletion of sEH on seizure-induced neuroinflammatory responses and the development of epilepsy were evaluated. In the hippocampus of WT mice, sEH was mainly expressed in astrocytes (GFAP(+)), neurons (NeuN(+)) and scattered microglia (Iba-1(+)) in the regions of CA1, CA3 and dentate gyrus. Expression of sEH was significantly increased on day 7, 14, 21 and 28 after pilocarpine-induced status epilepticus (SE). Administration with sEH inhibitors attenuated the SE induced up-regulation of interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), the degradation of EETs, as well as IkappaB phosphorylation. Following treatment with AUDA, the frequency and duration of spontaneous motor seizures in the pilocarpine-SE mice were decreased and the seizure-induction threshold of the fully kindled mice was increased. Up-regulation of hippocampal IL-1beta and IL-6 was found in both WT and sEH KO mice after successful induction of SE. Notably, sEH KO mice were more susceptible to seizures than WT mice. Seizure related neuroinflammation and ictogenesis were attenuated by pharmacological inhibition of sEH enzymatic activity but not by sEH genetic deletion. Therefore, sEH may play an important role in the generation of epilepsy. Furthermore, the effectiveness of AUDA in terms of anti-inflammatory and anti-ictogenesis properties suggests that it may have clinical therapeutic implication for epilepsy in the future, particularly when treating temporal lobe epilepsy. PMID- 25135859 TI - Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus involving MU-calpain activation. AB - Transient forebrain ischemia (TFI) leads to hippocampal CA1 pyramidal cell death which is aggravated by glucocorticoids (GC). It is unknown how GC affect apoptosis and necrosis in cerebral ischemia. We therefore investigated the co localization of activated caspase-3 (casp-3) with apoptosis- and necrosis-like cell death morphologies in CA1 of rats treated with dexamethasone prior to TFI (DPTI). In addition, apoptosis- (casp-9, casp-3, casp-3-cleaved PARP and cleaved alpha-spectrin 145/150 and 120kDa) and necrosis-related (calpain-specific casp-9 cleavage, MU-calpain upregulation and cleaved alpha-spectrin 145/150kDa) cell death mechanisms were investigated by Western blot analysis. DPTI expedited CA1 neuronal death from day 4 to day 1 and increased the magnitude of CA1 neuronal death from 66.2% to 91.3% at day 7. Furthermore, DPTI decreased the overall (days 1-7) percentage of dying neurons displaying apoptosis-like morphology from 4.7% to 0.3% and, conversely, increased the percentage of neurons with necrosis-like morphology from 95.3% to 99.7%. In animals subjected to TFI without dexamethasone (ischemia-only), 7.4% of all dying CA1 neurons were casp-3-immunoreactive (IR), of which 3.1% co-localized with apoptosis-like and 4.3% with necrosis-like changes. By contrast, DPTI decreased the percentage of dying neurons with casp-3 IR to 1.4%, of which 0.3% co-localized with apoptosis-like changes and 1.1% with necrosis-like changes. Western blot analysis from DPTI animals showed a significant elevation of MU-calpain, a calpain-produced necrosis-related casp-9 fragment (25kDa) and cleavage of alpha-spectrin into 145/150kDa fragments at day 4, whereas in ischemia-only animals a significant increase of casp-3-cleaved PARP, cleavage of alpha-spectrin into 145/150 and 120kDa fragments was detected at day 7. We conclude that DPTI, in addition to augmenting and expediting CA1 neuronal death, causes a shift from apoptosis-like cell death to necrosis involving MU-calpain activation. PMID- 25135860 TI - Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. AB - The term cirrhosis-associated immune dysfunction refers to the main syndromic abnormalities of immune function, immunodeficiency and systemic inflammation that are present in cirrhosis. The course of advanced cirrhosis, regardless of its aetiology, is complicated by cirrhosis-associated immune dysfunction and this constitutes the pathophysiological hallmark of an increased susceptibility to bacterial infection, distinctive of the disease. Cirrhosis impairs the homeostatic role of the liver in the systemic immune response. Damage to the reticulo-endothelial system compromises the immune surveillance function of the organ and the reduced hepatic synthesis of proteins, involved in innate immunity and pattern recognition, hinders the bactericidal ability of phagocytic cells. Systemic inflammation, in form of activated circulating immune cells and increased serum levels of pro-inflammatory cytokines, is the result of persistent episodic activation of circulating immune cells from damage-associated molecular patterns, released from necrotic liver cells and, as cirrhosis progresses, from pathogen-associated molecular patterns, released from the leaky gut. Cirrhosis associated immune dysfunction phenotypes switch from predominantly "pro inflammatory" to predominantly "immunodeficient" in patients with stable ascitic cirrhosis and in patients with severely decompensated cirrhosis and extra-hepatic organ failure (e.g. acute-on-chronic liver failure), respectively. These cirrhosis-associated immune dysfunction phenotypes represent the extremes of a spectrum of reversible dynamic events that take place during the course of cirrhosis. Systemic inflammation can affect the functions of tissue somatic cells and modify the clinical manifestation of cirrhosis. The best characterized example is the contribution of systemic inflammation to the haemodynamic derangement of cirrhosis, which correlates negatively with prognosis. PMID- 25135861 TI - Underestimation of occult hepatitis C virus infection in chronic haemodialysis and kidney transplant patients. PMID- 25135862 TI - MicroRNA-199a-5p inhibition enhances the liver repopulation ability of human embryonic stem cell-derived hepatic cells. AB - BACKGROUND & AIMS: Current hepatic differentiation protocols for human embryonic stem cells (ESCs) require substantial improvements. MicroRNAs (miRNAs) have been reported to regulate hepatocyte cell fate during liver development, but their utility to improve hepatocyte differentiation from ESCs remains to be investigated. Therefore, our aim was to identify and to analyse hepatogenic miRNAs for their potential to improve hepatocyte differentiation from ESCs. METHODS: By miRNA profiling and in vitro screening, we identified miR-199a-5p among several potential hepatogenic miRNAs. Transplantation studies of miR-199a 5p-inhibited hepatocyte-like cells (HLCs) in the liver of immunodeficient fumarylacetoacetate hydrolase knockout mice (Fah(-/-)/Rag2(-/-)/Il2rg(-/-)) were performed to assess their in vivo liver repopulation potential. For target determination, western blot and luciferase reporter assay were carried out. RESULTS: miRNA profiling revealed 20 conserved candidate hepatogenic miRNAs. By miRNA screening, only miR-199a-5p inhibition in HLCs was found to be able to enhance the in vitro hepatic differentiation of mouse as well as human ESCs. miR 199a-5p inhibition in human ESCs-derived HLCs enhanced their engraftment and repopulation capacity in the liver of Fah(-/-)/Rag2(-/-)/Il2rg(-/-) mice. Furthermore, we identified SMARCA4 and MST1 as novel targets of miR-199a-5p that may contribute to the improved hepatocyte generation and in vivo liver repopulation. CONCLUSIONS: Our findings demonstrate that miR-199a-5p inhibition in ES-derived HLCs leads to improved hepatocyte differentiation. Upon transplantation, HLCs were able to engraft and repopulate the liver of Fah(-/ )/Rag2(-/-)/Il2rg(-/-) mice. Thus, our findings suggest that miRNA modulation may serve as a promising approach to generate more mature HLCs from stem cell sources for the treatment of liver diseases. PMID- 25135863 TI - Vitamin D level and sustained virologic response to interferon-based antiviral therapy in chronic hepatitis C: a systematic review and meta-analysis. AB - BACKGROUND & AIMS: The baseline 25-hydroxyvitamin D (25[OH]D) level has recently been reported to be an independent predictor of sustained virologic response (SVR) to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV) for chronic hepatitis C virus (HCV) infection. However, studies have yielded inconsistent results. Thus, we conducted a systematic review and meta-analysis to clarify any association between baseline 25(OH)D level and SVR in HCV therapy. METHODS: Two reviewers searched four electronic databases (Medline, Embase, PubMed, and Cochrane trials register) and relevant international conference proceedings up to March 2014 for studies treating chronic HCV infection with PEG IFN plus RBV where baseline 25(OH)D level was tested. Studies involving patients with HIV co-infection, previous liver transplantation or those receiving vitamin D supplementation were excluded. The mean baseline 25(OH)D level was compared between those who achieved and those who failed to achieve SVR. Pooled standard difference in mean 25(OH)D level, odds ratios (OR) and 95% confidence intervals (CI) were calculated with the Comprehensive Meta-Analysis software (version 2.0) using a random effects model. RESULTS: 11 studies comprising 2605 patients were included in the meta-analysis. There was no significant association between the baseline mean 25(OH)D level and SVR (OR 1.44, 95% CI 0.92-2.26; p=0.11), either in patients infected with genotypes 1/4/5 (OR 1.48, 95% CI 0.94-2.34; p=0.09) or genotypes 2/3 (OR 1.51, 95% CI 0.26-8.87; p=0.65). CONCLUSIONS: The baseline 25(OH)D level is not associated with SVR to PEG-IFN plus RBV therapy in chronic HCV infection, regardless of genotype. Any effect of vitamin D supplementation on SVR is yet to be definitively determined. PMID- 25135864 TI - PegIFNalpha/ribavirin/protease inhibitor combination in severe hepatitis C virus associated mixed cryoglobulinemia vasculitis. AB - BACKGROUND & AIMS: The aim of this study was to analyse the safety and efficacy of the PegIFNalpha/ribavirin/protease inhibitor combination in severe and/or refractory hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis. METHODS: This prospective cohort study included 30 patients (median age 59 years [53-66] and 57% of women) with HCV-MC vasculitis. PegIFNalpha/ribavirin (for 48 weeks) was associated with telaprevir (375 mg three times daily, for 12 weeks, [n = 17]) or boceprevir (800 mg three times daily, for 44 weeks, (n = 13]). RESULTS: Twenty three patients (76.7%) were non-responders to previous antiviral therapy. At week 72, twenty patients (66.7%) were complete clinical and sustained virological responders. The cryoglobulin level decreased from 0.45 to 0 g/L (p<0.0001) and the C4 level increased from 0.09 to 0.14 g/L (p = 0.017). Complete clinical responders had a higher frequency of purpura (16/20 [80%] vs. 4/10 [40%], p = 0.045), and a trend towards lower frequency of neuropathy (9/20 (45%) vs. 8/10 [80%], p = 0.12) compared with partial responders. Serious adverse events occurred in 14 patients (46.6%) during the 72 weeks of follow-up. Twenty eight patients (93.3%) received erythropoietin, 14 (46.6%) had red blood cell transfusion and 2 (6.6%) received granulocyte stimulating agent. The baseline factors associated with serious adverse events included liver fibrosis (p = 0.045) and a low platelet count (p = 0.021). CONCLUSIONS: The PegIFNalpha/ribavirin/protease inhibitor combination is highly effective in severe and/or refractory HCV-MC at the cost of frequent side effects. Baseline platelet count and liver fibrosis are useful in guiding treatment decisions. PMID- 25135865 TI - Advantage of bariatric surgery for patients with type 2 diabetes mellitus. PMID- 25135866 TI - Reply to: "underestimation of occult hepatitis C virus infection in chronic haemodialysis and kidney transplant patients". PMID- 25135869 TI - Revascularization of living-donor kidney transplant with multiple arteries: long term outcomes using the inferior epigastric artery. AB - OBJECTIVE: To study the safety and long-term outcomes of use of the inferior epigastric artery (IEA) for revascularization of small accessory kidney arteries (3 mm or less). MATERIALS AND METHODS: Data of 602 living-donor kidney transplants were reviewed. Age was 37.4 +/- 15 years (range, 3-78 years). Multiple arteries were present in 98 kidneys (16.3%); of these, 83 (84.7%) had 2 and arteries and 15 (15.3%) had 3 arteries. In 21 kidneys (21.4%) with multiple arteries (group I [GI]), the IEA was used for reconstruction. Four (14.3%) had 3 arteries, and 17 (85.7%) had 2 arteries. In 77 patients (group II [GII]), the inferior accessory renal artery was reconstructed with a side-to-side or an end to-side anastomosis to the main renal artery. Follow-up was 43.8 +/- 38.1 months (range, 1-124 months). The Fisher exact test and the 2-tailed t test were used for statistical analysis. RESULTS: Delayed graft function occurred in 1 GI patient (4.8%) and in 5 GII patients (6.5%; P >.05). One partial renal infarction occurred in each group (4.8% vs 1.3%; P >.05). There was 1 urinary fistula in GI and 3 urinary fistulas and 1 ureteral stenosis in GII (P >.05). One graft (4.8%) lost function in GI and 5 (6.5%) in GII (P >.05). Eleven patients (53.4%) were hypertensive in GI and 53 (68.8%) in GII (P >.05). CONCLUSION: The use of the IEA for revascularization of a living-donor kidney transplant with multiple arteries is safe and effective, yielding similar long-term outcomes compared with the standard technique. Use of the IEA avoids the risks of manipulation of the main renal artery. PMID- 25135867 TI - Statin use is associated with a reduced risk of fibrosis progression in chronic hepatitis C. AB - BACKGROUND & AIMS: Therapies that slow fibrosis progression in chronic liver disease are needed. Animal models have demonstrated that statins prevent the progression of hepatic fibrosis, but human data is lacking so far. We evaluated the association between statins and fibrosis progression in the HALT-C trial cohort. METHODS: Subjects with chronic hepatitis C (CHC) and advanced hepatic fibrosis underwent serial liver biopsies over 3.5 years. The primary outcome was a ? 2-point increase in the Ishak fibrosis score on at least one of two serial biopsies. We used complementary log-log regression analysis to assess the association between statins and fibrosis progression among subjects without baseline cirrhosis. RESULTS: Fibrosis progression occurred in 3/29 (10%) statin users and 145/514 (29%) non-users. The unadjusted hazard ratio (HR) for fibrosis progression among statin users compared to non-users was 0.32 (95% CI 0.10-0.99). This association remained significant after adjusting for established predictors of histological outcome, including body mass index, platelets and hepatic steatosis (adjusted HR 0.31; 95% CI 0.10-0.97). The mean change in Ishak fibrosis score over the 3.5 year study period was -0.34 (SE 0.18) for statin users compared to +0.42 (SE 0.07) for non-users (p = 0.006, after adjustment for baseline fibrosis score). CONCLUSIONS: Statin use is associated with a reduced risk of fibrosis progression in advanced CHC. Our findings suggest a potential role for statins in preventing liver disease progression. PMID- 25135868 TI - The genomic landscape of hepatoblastoma and their progenies with HCC-like features. AB - BACKGROUND & AIMS: Hepatoblastoma (HB) is the most common childhood liver cancer and occasionally presents with histological and clinical features reminiscent of hepatocellular carcinoma (HCC). Identification of molecular mechanisms that drive the neoplastic continuation towards more aggressive HCC phenotypes may help to guide the new stage of targeted therapies. METHODS: We performed comprehensive studies on genetic and chromosomal alterations as well as candidate gene function and their clinical relevance. RESULTS: Whole-exome sequencing identified HB as a genetically very simple tumour (2.9 mutations per tumour) with recurrent mutations in beta-catenin (CTNNB1) (12/15 cases) and the transcription factor NFE2L2 (2/15 cases). Their HCC-like progenies share the common CTNNB1 mutation, but additionally exhibit a significantly increased mutation number and chromosomal instability due to deletions of the genome guardians RAD17 and TP53, accompanied by telomerase reverse-transcriptase (TERT) promoter mutations. Targeted genotyping of 33 primary tumours and cell lines revealed CTNNB1, NFE2L2, and TERT mutations in 72.5%, 9.8%, and 5.9% of cases, respectively. All NFE2L2 mutations affected residues of the NFE2L2 protein that are recognized by the KEAP1/CUL3 complex for proteasomal degradation. Consequently, cells transfected with mutant NFE2L2 were insensitive to KEAP1-mediated downregulation of NFE2L2 signalling. Clinically, overexpression of the NFE2L2 target gene NQO1 in tumours was significantly associated with metastasis, vascular invasion, the adverse prognostic C2 gene signature, as well as poor outcome. CONCLUSIONS: Our study demonstrates the importance of CTNNB1 mutations and NFE2L2-KEAP1 pathway activation in HB development and defines loss of genomic stability and TERT promoter mutations as prominent characteristics of aggressive HB with HCC features. PMID- 25135870 TI - Reconstructive strategy and classification of penoscrotal defects. AB - OBJECTIVE: To classify defects in the penoscrotal region according to their specific anatomic sites. METHODS: From January 2002 to December 2012, 20 male patients underwent reconstruction for penoscrotal defects. The causative factors were Fournier's gangrene in 12 patients, extramammary Paget's disease in 4, skin tumors in 3, and deformity after a burn injury in 1. The defects were categorized according to their anatomic location: penis (P), and right (r) and left (l) scrotum (Sr and Sl), inguinal area (Ir and Il), and perianal area (Ar and Al). RESULTS: Seven patients with defects in the penis received skin grafts. Defects affecting more than 2 anatomic regions or extensive defects (>100 cm(2)) were reconstructed by free tissue transfer. Other defects were reconstructed by perforator-based island flap coverage. All of the flaps survived without complications. CONCLUSION: We introduce a classification that provides a simple way to specify the anatomic location and extent of a defect. This classification will permit more effective and straightforward reconstruction in the penoscrotal region. PMID- 25135872 TI - Comparison of treatment strategies for thoracic endograft infection. AB - OBJECTIVE: Endograft infection after thoracic endovascular aortic repair (TEVAR) is associated with a substantial mortality rate that exceeds 70% in the largest published series. The aim of this study was to review all published reports on infection after TEVAR treated with either preservation of the endograft or surgical excision of the stent graft with the intention of providing a comparison of the safety, efficacy, and durability of the two different treatment strategies. METHODS: An extensive electronic health database search was undertaken to identify all articles that were published up to December 2013 reporting on endograft infection after TEVAR. Overall, 55 patients treated with endograft preservation (group A) and 41 patients treated with endograft explantation (group B) were included in this review. RESULTS: The most frequently isolated microorganisms were Streptococcus species (29.4%) and Staphylococcus species (29.4%). The mortality for both groups was 66.6%. The in-hospital mortality rate in group A was 42% and reached 81.8% in a mean follow-up period of 8.6 months. The in-hospital mortality rate in group B was 36.6%. Four (9.7%) further deaths due to reinfection or fistula recurrence were recorded in a mean follow-up period of 15.3 months, leading to an overall mortality of 46.3%. The meta-analysis showed a trend of better outcome with endograft explantation compared with endograft preservation (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.18-1.48). In group A, a trend of better outcome was revealed when drainage and repair of the fistula were applied (OR, 2.22; 95% CI, 0.55 8.90). A trend of worse outcomes was detected in fistula patients compared with nonfistula patients (OR, 1.26; 95% CI, 0.43-3.74). CONCLUSIONS: Endograft preservation seems not a durable option. It can be offered to patients who refuse surgery or as a palliative option or bridging procedure for severely ill patients. Compared with antibiotic therapy alone, antibiotic therapy followed by drainage and repair of the fistula may control the sepsis, providing, however, mainly a temporary benefit. The presence of fistula is a predictor of dismal outcome. Endograft explantation remains the "gold standard" of treatment. The mortality rate of surgical conversion is much higher in the presence of fistula. PMID- 25135871 TI - Evaluation of neutrophil gelatinase-associated lipocalin, interleukin-18, and cystatin C as molecular markers before and after unilateral shock wave lithotripsy. AB - OBJECTIVE: To investigate the impact of shock wave lithotripsy (SWL) on renal tissues using neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and interleukin 18 (IL-18) levels in serum and urine and to examine the relationship of these biomarkers with patient and calculus characteristics as well as SWL treatment parameters. MATERIALS AND METHODS: Thirty-seven patients with renal calculi were included in this study. Blood and urine samples were attained from each patient at 4 time points; immediately before SWL, 6 hours after, 3 days after, and 10 days after the SWL. A new generation lithotripter was used for all cases. Serum and urine NGAL concentrations were measured using commercially available enzyme-linked immunosorbent assay kits according to manufacture's protocol. The concentration of cystatin C was measured in serum, whereas IL-18 concentration was assessed in urine. RESULTS: There were no statistically significantly differences in the levels of NGAL in serum and urine before and after SWL. The mean levels of cystatin C in serum appeared significantly higher 3 and 10 days after SWL. No statistically significant differences were identified between levels of IL-18 before and after SWL. Patients with diabetes mellitus demonstrated significantly higher baseline cystatin C levels. There was no correlation between calculus characteristics or treatment parameters and the levels of all 3 biomarkers after SWL. CONCLUSION: The results of this study indicate that SWL is associated with minimal acute injury to renal tissues. Our findings support the safety profile of new generation lithotripters, provided orthodox indications and treatment principles are followed. PMID- 25135874 TI - The impact of intraoperative shunting on early neurologic outcomes after carotid endarterectomy. AB - BACKGROUND: Although the need for intraoperative shunting during carotid endarterectomy (CEA) is intensely debated, relatively few studies have compared the neurologic outcomes of patients undergoing CEA with or without shunts. The objective of our analysis was to determine the impact of intraoperative shunting during CEA on the incidence of postoperative stroke. METHODS: The 2012 CEA targeted American College of Surgeons National Surgical Quality Improvement Program database was used for this analysis. The preoperative and operative characteristics of patients undergoing CEA with or without intraoperative shunting were compared. From this overall sample, propensity score techniques were then used to match patients with or without intraoperative shunting for a number of variables, including age, degree of ipsilateral and contralateral carotid stenosis, presence of several anatomic or physiologic risk factors, anesthesia modality, and use of patch angioplasty vs primary arteriotomy closure. The 30-day postoperative mortality and combined stroke/transient ischemic attack (TIA) rates of this matched cohort were then compared. A similar analysis was also performed on a subgroup of patients with severe stenosis or occlusion of the contralateral carotid artery. RESULTS: A total of 3153 patients were included for initial analysis (2023 "no-shunt" patients vs 1130 "shunt" patients). From this overall sample, propensity score matching yielded a cohort of 1072 patients with or without intraoperative shunt placement who were well matched for all known patient- and procedure-related factors. There was no significant difference in the incidence of postoperative stroke/TIA between the two groups of this matched cohort (3.4% in the no-shunt group vs 3.7% in the shunt group; P = .64). Analysis of a similarly well matched subgroup of patients with severe stenosis or occlusion of the contralateral carotid artery demonstrated a statistically nonsignificant increase in the incidence of postoperative stroke/TIA with the use of intraoperative shunting (4.9% in the no-shunt group vs 9.8% in the shunt group; P = .08). CONCLUSIONS: There is no clinical benefit to intraoperative shunting during CEA, even in patients who may be at high risk for intraoperative cerebral hypoperfusion due to severe stenosis or occlusion of the contralateral carotid artery. PMID- 25135873 TI - One-year patency rate of native arteriovenous fistulas reconstructed by vascular stripping in hemodialysis patients with venous neointimal hyperplasia. AB - OBJECTIVE: There are limited therapeutic measures for stenosis of arteriovenous fistulas (AVFs) due to venous neointimal hyperplasia (VNH). In the current retrospective study, we reviewed the clinical data of hemodialysis patients who underwent AVF reconstruction by VNH stripping. The primary measure of interest was the secondary patency rate of the restored AVF. METHODS: The study included hemodialysis patients who underwent AVF reconstruction by VNH stripping (group A), AVF reconstruction proximal to the original fistula (group B), or creation of a new AVF (group C). Patency was evaluated immediately after the surgery and at follow-up visits. RESULTS: Of 353 patients who underwent AVF reconstructions, 327 (91.9%) were for late AVF failure. The final analysis included 305 patients: 76, 128, and 101 patients in groups A, B, and C, respectively. The three groups were comparable in age, sex, causes for AVF, AVF sites, and the artery for the AVF (P > .05). At 3-month follow-up, the secondary AVF patency rate was comparable across the three groups at 93.4%, 92.2%, and 92.1% in groups A, B, and C, respectively. The patency rate at 6 and 12 months was also comparable across groups A, B, and C at 89.5%, 89.8%, and 88.1% at 6 months and 84.2%, 85.9%, and 81.2% at 12 months, respectively. CONCLUSIONS: Reconstructing the AVF by surgically removing VNH is an effective technique for late hemodialysis access failure, with maximal preservation of blood vessels. PMID- 25135875 TI - Percutaneous radial access for peripheral transluminal angioplasty. AB - OBJECTIVE: The radial approach is currently gaining popularity in the setting of coronary percutaneous transluminal angioplasty (PTA) because it decreases the incidence of vascular complications. This study reports our initial results with radial access for peripheral PTA. METHODS: Between November 2011 and January 2014, we performed peripheral PTA in 526 patients. PTA was performed through left radial access in 24 ambulatory patients (4.6%) presenting with TransAtlantic Inter-Society Consensus A or B lesions on preoperative computed tomography angiography. Materials included a 110-cm-long introducer, a 0.018-inch 400-cm long wire, 150-cm-long angiography catheters, 180-cm-long shaft balloons and stents. Data were prospectively collected. RESULTS: There were 22 men (92%), median age was 65 years (range, 45-88 years), and 38 target lesions were treated. Indication for revascularization was disabling claudication in 22 patients (92%) and critical ischemia in two (8%). Indication for choosing the radial approach was bilateral hostile groins in 12 patients (50%), bilateral infrainguinal lesions in 4 (17%), need for a contralateral femoral approach in the setting of kissing iliac stents or bifurcated surgical aortic grafts in 3 (13%), and elective in 5 (21%). Radial puncture failed in one patient (4%), and PTA was performed through brachial access. Technical success was 91% (20 of 22 patients). Thirty-seven stents were implanted. Total procedure duration was 45 minutes (range, 30-120 minutes). Fluoroscopy time was 9 minutes (range, 5-35 minutes), and 40 mL (range, 20-90 mL) of contrast was necessary. Radial artery rupture secondary to spasm was noted at the end of the procedure in two patients (8%). All patients could ambulate 2 hours after the procedure. No patient died. Median follow-up was 8 months (range, 1-23 months). Three radial arteries (13%) were occluded at the last follow-up. At 6 months, freedom from target lesion revascularization and target vessel revascularization were 91% and 91%, respectively, for iliac lesions and 93% and 86%, respectively, for infrainguinal lesions. CONCLUSIONS: This study demonstrates the feasibility of radial access for peripheral PTA. Radial access could represent an alternative to brachial access for peripheral and visceral interventions. Although complication rates of the present series are concerning, larger studies are needed to determine the role of transradial PTA once the learning curve is overcome. A wider diffusion of the technique mandates (1) smaller-diameter sheaths, (2) longer shaft devices, and (3) the development of specifically designed rescue devices such as covered stents and thromboaspiration catheters. PMID- 25135876 TI - Professionalism and the work-life balance. PMID- 25135877 TI - Computed tomography-guided reoperation for neurogenic thoracic outlet syndrome. AB - OBJECTIVE: Persistent or recurrent symptoms after surgical treatment for neurogenic thoracic outlet syndrome (nTOS) is a problem commonly encountered by high-volume referral centers. The mechanical etiology patterns at reoperation include (1) inadequate previous rib resection, (2) rib regrowth, (3) scar tissue formation, or (4) intact scalene muscle. Reoperative TOS surgery has significant potential morbidity, and therefore, careful patient selection and meticulous planning are required. This study evaluated the utility of multidetector computed tomography (CT) in the differential diagnosis of patients with recurrent or persistent nTOS. METHODS: A retrospective record review was performed of a nTOS referral practice of patients treated from 2003 to 2012 to focus on patients reoperated on for recurrent or persistent symptoms. In 2003, a dedicated high resolution multidetector TOS CT protocol was established to assist in clinical decision making and reoperative planning. A single designated radiologist interpreted all CT images. Imaging, patient clinical characteristics, interventions, and outcomes were reviewed. RESULTS: The study group included 20 reoperations for recurrent (n = 15) or persistent (n = 5) symptoms. Mean age was 35 years, and 60% of redo cases were in women. Preoperative CT imaging demonstrated the following anatomic patterns: inadequate previous rib resection in 5 (25%), rib regrowth in 5 (25%), scar tissue formation in 10 (50%), and intact scalene muscle in 3 (15%). Operative findings concurred with preoperative imaging in 85% of patients. There were no neurovascular injuries and no major complications. At a mean follow-up of 43 months, improvement or resolution of symptoms was significant in nine patients (45%), moderate in seven (35%), and minimal in four (20%). CONCLUSIONS: Recurrent/persistent nTOS is an often-vexing problem with challenging solutions. These results demonstrate the utility of a TOS protocol CT scan in providing correlative objective findings and in assisting with reoperative planning. Positive radiographic findings that correlate with patient symptoms inform the decision to reoperate. PMID- 25135880 TI - Obstetrics-based clinical immersion of a multinational team of biomedical engineering students in Ghana. PMID- 25135879 TI - NG as a novel nitric oxide donor induces apoptosis by increasing reactive oxygen species and inhibiting mitochondrial function in MGC803 cells. AB - NG, O(2)-(2,4-dinitro-5-{[2-(12-en-28-beta-D-galactopyranosyl-oleanolate-3-yl) oxy-2-oxoethyl] amino} phenyl) 1-(N-hydroxyethylmethylamino) diazen-1-ium-1,2 diolate, was identified in our laboratory as a novel nitric oxide-releasing prodrug with antitumor effects. A previous study showed that NG inhibited cell growth, and induced apoptosis in HepG2 cells. In this study, the inhibitory effects of NG on the viability of MGC803 cells were examined using methylthiazolyl tetrazolium biomide (MTT) assay, neutral red assay and trypan blue exclusion test. The results showed that NG had strong cytotoxicity to induce apoptosis, which was characterized by a significant externalization of phosphatidylserine, nuclear morphological changes and enhanced Bax-to-Bcl-2 ratio. Moreover, the release of cytochrome c (Cyt c) from mitochondria and the activation of caspase-9/3 were also detected, indicating that NG may induce apoptosis through a mitochondrial-mediated pathway. NG induced mitochondrial dysfunction in MGC803 cells by altering membrane potential (?Psim), the inhibition of complexes I, II and IV consequently decreasing ATP level. Furthermore, the treatment of MGC803 cells with NG caused a marked rise in oxidative stress as characterized by accumulation of reactive oxygen species (ROS), excessive malondialdehyde (MDA) production and a reduction in glutathione hormone (GSH) level and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. In addition, pretreatment with N-acetylcysteine (NAC), a GSH synthesis precursor, was partially protective against the NG-induced ROS generation and cell apoptosis. In contrast, pretreatment of MGC803 cells with L buthionine-S, R-sulfoximine (BSO), a GSH synthesis inhibitor, increased the ROS levels, and aggravated cell apoptosis by NG. These results suggest that NG induced apoptosis in MGC803 cells is mediated, at least in part, by the increase in ROS production, oxidative stress and mitochondrial dysfunction. PMID- 25135878 TI - Ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances HBV specific humoral and CTL immune responses in vivo. AB - Therapeutic strategies based on an enhanced hepatitis B virus (HBV)-specific cytotoxic T lymphocyte (CTL) activity may eradicate HBV. We previously verified that a fusion protein ubiquitin (Ub)-hepatitis B core antigen (HBcAg)-cytoplasmic transduction peptide (CTP) can enter the cytoplasm of dendritic cells and enhance T cell response to generate HBV-specific CTLs efficiently in vitro. Ub, a marker of protein degradation, may promote the generation of peptides appropriate for major histocompatibility complex class I presentation. In the present study, the specific immune responses of the fusion protein Ub-HBcAg-CTP in BALB/c mice were evaluated and the underlying mechanisms were investigated. Results showed that Ub HBcAg-CTP increased the anti-HBcAg titer and produced the cytokines IFN-gamma and IL-2. This fusion protein also induced higher percentages of IFN-gamma(+)CD8(+) cells and specific CTL responses. Ub-HBcAg-CTP could also upregulate the expressions of Jak2, Tyk2, STAT1, and STAT4 in T lymphocytes. In conclusion, Ub HBcAg-CTP enhanced cellular and humoral immune responses and induced robust HBV specific CTL activities in BALB/c mice. PMID- 25135881 TI - Factors associated with the use of prenatal corticosteroids in the management of preterm delivery in Chinese hospitals. AB - OBJECTIVE: To assess the prevalence of the use of prenatal corticosteroids (PCS) in the management of preterm delivery and the factors associated with PCS administration. METHODS: A secondary analysis was performed of a cross-sectional study conducted in 21 Chinese healthcare facilities between November 2010 and January 2011. The medical records of women who delivered preterm were reviewed. Associations between PCS administration and individual and organizational-level factors were determined. RESULTS: The study population comprised 659 women who delivered at 20 facilities. PCS were given to 158 (68.1%) of 232 women delivering after 27-34 weeks of pregnancy and 119 (27.9%) of 427 delivering after 35-36 weeks. Teenaged girls were less likely to receive PCS after 27-34 weeks than were women aged 20-35 years (odds ratio [OR] 0.22; 95% confidence interval [CI] 0.07 0.70). Among women who delivered after 35-36 weeks, the odds of receiving PCS were lower in urban hospitals than in periurban or rural hospitals (OR 0.04; 95% CI 0.00-0.44), and there was significant hospital-level variance with regard to the administration of PCS (P<0.05). CONCLUSION: Generally, PCS were underprescribed to women at risk of preterm delivery and many women received the treatment after 35-36 weeks of pregnancy, when it might not have been effective. PMID- 25135882 TI - Overweight Misperception among Adolescents in the United States. AB - The purpose of this study was to examine the discrepancies between perceived and reported overweight status among U.S. adolescents (n>70,000), and to identify factors contributing to such discrepancies. We used the YRBSS data (years 2001 2009) and found statistically significant, gender and race specific discrepancies between perceived and reported overweight status. Factors such as BMI, school performance, and being sexually active are additional predictors of overweight misperception. The findings suggest that evidence based strategies should be employed to help adolescents establish correct weight perception. These strategies should also be tailored based on gender, race, and weight perception of target audience. PMID- 25135883 TI - Using the theory of planned behavior to understand caregivers' intention to serve sugar-sweetened beverages to non-Hispanic black preschoolers. AB - The purpose of this correlational study was to determine the ability the Theory of Planned Behavior (TPB) to explain caregivers' intention to serve sugar sweetened beverages to non-Hispanic black preschoolers. A sample of 165 caregivers of non-Hispanic black children preschoolers completed a written questionnaire. Multiple regression with path analysis confirmed the relationships of attitude and subjective norm, but not perceived behavioral control (PBC),with intention. After removing PBC, the model accounted for 45.1% of variance in intention. Nurses and other health care professionals can use these findings to tailor behaviorally-based obesity prevention programs at the individual, family, and community-based levels. PMID- 25135884 TI - An in vitro assay to study chikungunya virus RNA synthesis and the mode of action of inhibitors. AB - Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that causes severe persistent arthralgia. To better understand the molecular details of CHIKV RNA synthesis and the mode of action of inhibitors, we have developed an in vitro assay to study CHIKV replication/transcription complexes isolated from infected cells. In this assay (32)P-CTP was incorporated into the CHIKV genome, subgenomic (sg) RNA and into a ~7.5 kb positive-stranded RNA, termed RNA II. We mapped RNA II, which was also found in CHIKV-infected cells, to the 5' end of the genome up to the start of the sgRNA promoter region. Most of the RNA-synthesizing activity, negative-stranded RNA and a relatively large proportion of nsP1 and nsP4 were recovered from a crude membrane fraction obtained by pelleting at 15,000 G: . Positive-stranded RNA was mainly found in the cytosolic S15 fraction, suggesting it was released from the membrane-associated replication/transcription complexes (RTCs). The newly synthesized RNA was relatively stable and remained protected from cellular nucleases, possibly by encapsidation. A set of compounds that inhibit CHIKV replication in cell culture was tested in the in vitro RTC assay. In contrast to 3'dNTPs, chain terminators that acted as potent inhibitors of RTC activity, ribavirin triphosphate and 6-aza-UTP did not affect the RNA synthesizing activity in vitro. In conclusion, this in vitro assay for CHIKV RNA synthesis is a useful tool for mechanistic studies on the RTC and mode of action studies on compounds with anti-CHIKV activity. PMID- 25135885 TI - Two amino acid substitutions in the haemagglutinin of the 2009 pandemic H1N1 virus decrease direct-contact transmission in guinea pigs. AB - The 2009 pandemic H1N1 influenza A virus spread across the globe and caused the first influenza pandemic of the 21st century. Many of the molecular factors that contributed to the airborne transmission of this pandemic virus have been determined; however, the direct-contact transmission of this virus remains poorly understood. In this study, we report that a combination of two mutations (N159D and Q226R) in the haemagglutinin (HA) protein of the representative 2009 H1N1 influenza virus A/California/04/2009 (CA04) caused a switch in receptor binding preference from the alpha2,6-sialoglycan to the alpha2,3-sialoglycan receptor, and decreased the binding intensities for both glycans. In conjunction with a significantly decreased replication efficiency in the nasal epithelium, this limited human receptor binding affinity resulted in inefficient direct-contact transmission of CA04 between guinea pigs. Our findings highlight the role of the HA gene in the transmission of the influenza virus. PMID- 25135886 TI - Sporothrix schenckii complex biology: environment and fungal pathogenicity. AB - Sporothrix schenckii is a complex of various species of fungus found in soils, plants, decaying vegetables and other outdoor environments. It is the aetiological agent of sporotrichosis in humans and several animals. Humans and animals can acquire the disease through traumatic inoculation of the fungus into subcutaneous tissue. Despite the importance of sporotrichosis, it being currently regarded as an emergent disease in several countries, the factors driving its increasing medical importance are still largely unknown. There have only been a few studies addressing the influence of the environment on the virulence of these pathogens. However, recent studies have demonstrated that adverse conditions in its natural habitats can trigger the expression of different virulence factors that confer survival advantages both in animal hosts and in the environment. In this review, we provide updates on the important advances in the understanding of the biology of Spor. schenckii and the modification of its virulence linked to demonstrated or putative environmental factors. PMID- 25135887 TI - Adventitious agents in viral vaccines: lessons learned from 4 case studies. AB - Since the earliest days of biological product manufacture, there have been a number of instances where laboratory studies provided evidence for the presence of adventitious agents in a marketed product. Lessons learned from such events can be used to strengthen regulatory preparedness for the future. We have therefore selected four instances where an adventitious agent, or a signal suggesting the presence of an agent, was found in a viral vaccine, and have developed a case study for each. The four cases are: a) SV40 in polio vaccines; b) bacteriophage in measles and polio vaccines; c) reverse transcriptase in measles and mumps vaccines; and d) porcine circovirus and porcine circovirus DNA sequences in rotavirus vaccines. The lessons learned from each event are discussed. Based in part on those experiences, certain scientific principles have been identified by WHO that should be considered in regulatory risk evaluation if an adventitious agent is found in a marketed vaccine in the future. PMID- 25135888 TI - The management of secondary lower limb lymphoedema in cancer patients: a systematic review. AB - BACKGROUND: Lower limb lymphoedema is a recognised complication of cancer commonly encountered in palliative care, associated with reduced mobility and poor quality of life. AIM: To evaluate the available evidence for the treatment of secondary lower limb lymphoedema in patients with malignancies. DESIGN: A systematic review of the literature. DATA SOURCES: The MEDLINE, Embase, LILACS, Science Citation Index, Cochrane Databases and conference proceedings for published data from date of inception to July 2014 were searched. Relevant unpublished studies via relevant databases, Internet searches and hand-searches of the bibliographies of relevant papers were performed. RESULTS: From 1617 citations, 32 papers were selected for full-text assessment. Two randomised trials and five observational studies were identified. The two randomised controlled trials evaluated graded compression stockings and Coumarin capsules, respectively. The five observational studies evaluated lymphovenous microsurgical shunts, pneumatic compression devices, compression bandages alone, manual lymphatic drainage with compression and a herbal remedy combining Coumarin, Ginkgo and Melitoto (with or without manual lymphatic drainage), respectively. The extracted studies showed substantial heterogeneity. Hence, a meta-analysis was inappropriate and not performed. CONCLUSION: Few studies have evaluated the clinical effectiveness and potential side effects of treatments for lower limb lymphoedema. Moreover, symptoms and quality-of-life assessments were inconsistently reported. All included studies report lower limb volume reduction after treatment, which includes complex decongestion therapy, graded compression stockings and lymphovenous microsurgical shunts. Adequately powered randomised controlled trials of these interventions are recommended. Effort should be made to establish standardised outcomes, to minimise bias and to improve reporting quality in future trials of treatment for lower limb lymphoedema. PMID- 25135889 TI - The role of phage display in therapeutic antibody discovery. AB - Phage display involves the expression of selected proteins on the surface of filamentous phage through fusion with phage coat protein, with the genetic sequence packaged within, linking phenotype to genotype selection. When combined with antibody libraries, phage display allows for rapid in vitro selection of antigen-specific antibodies and recovery of their corresponding coding sequence. Large non-immune and synthetic human libraries have been constructed as well as smaller immune libraries based on capturing a single individual's immune repertoire. This completely in vitro process allows for isolation of antibodies against poorly immunogenic targets as well as those that cannot be obtained by animal immunization, thus further expanding the utility of the approach. Phage antibody display represents the first developed methodology for high throughput screening for human therapeutic antibody candidates. Recently, other methods have been developed for generation of fully human therapeutic antibodies, such as single B-cell screening, next-generation genome sequencing and transgenic mice with human germline B-cell genes. While each of these have their particular advantages, phage display has remained a key methodology for human antibody discovery due its in vitro process. Here, we review the continuing role of this technique alongside other developing technologies for therapeutic antibody discovery. PMID- 25135892 TI - Solution to the challenging part of the Shamrock method during lumbar plexus block. PMID- 25135891 TI - Emergence agitation: is there a European consensus? PMID- 25135893 TI - Cut tracheal tube and GlideRite Rigid Stylet. PMID- 25135894 TI - Does adding milk to tea delay gastric emptying? PMID- 25135895 TI - (Bright) future of dynamic parameters is in the operating theatre. PMID- 25135896 TI - Dynamic parameters in the operating theatre: brightness goes with shadows. PMID- 25135897 TI - Making bisoprolol a perioperative agent. PMID- 25135898 TI - Benefits of continuous capnography monitoring for intensive care patients significantly outweigh any risks. PMID- 25135899 TI - Doses and effects of levobupivacaine and bupivacaine for spinal anaesthesia. PMID- 25135900 TI - The (Correct) use of capnography will reduce airway complications in intensive care. PMID- 25135907 TI - Data protection and epidemiological research: a new EU regulation is in the pipeline. PMID- 25135909 TI - Quantitative effect of natural killer-cell licensing on hepatocellular carcinoma recurrence after curative hepatectomy. AB - Natural killer (NK) cells have a potential role in immune surveillance of hepatocellular carcinoma (HCC). Self-recognition of human leukocyte antigens (HLA) through killer immunoglobulin-like receptors (KIR) confers competence to NK cells-a process termed "licensing." We investigated the effect of NK-cell licensing on the susceptibility of patients to HCC recurrence. A total of 170 Japanese patients with HCC who underwent primary curative hepatectomy between 1996 and 2010 were enrolled in this study. The median follow-up period was 5.4 years. We analyzed their KIR-HLA genotypes with sequence-specific polymorphism based typing and estimated their susceptibility to HCC recurrence by performing propensity score-matching analyses. The presence of KIR2DL1-C2, KIR2DL2-C1, KIR3DL1-BW4, or KIR3DL2-A3/11, functional compound genotypes that intrinsically license NK cells, did not markedly affect HCC recurrence. However, the multiplicity of those compound KIR-HLA genotypes was significantly associated with the HCC recurrence rate, i.e., the cumulative risk of recurrence in patients with at least three compound genotypes was significantly lower than that in patients with one or two compound genotypes, suggesting that the effect of NK cell licensing on HCC recurrence is quantitative. Patients at high risk of HCC recurrence after curative hepatectomy could be identified by KIR-HLA genotyping. PMID- 25135910 TI - How well informed is the informed consent for cancer clinical trials? AB - AIMS: The purpose of this study was to analyze the content of informed consent forms for clinical trials in medical oncology to assess readability, determine their completeness, and identify any shortcomings. METHODS: Informed consent forms for Phase I-III studies that were conducted at two tertiary care cancer centers over a 3-year period were reviewed. Information pertaining to length of the informed consent form, research regimen/methods, treatment agent, potential risks, and benefits was extracted. The reading level was assessed by Flesch Kincaid and Gunning-Fog index readability tests. RESULTS: All of the 112 informed consent forms clearly stated the voluntary nature of participation. Nearly one half of the forms (51.8%) were of Phase I studies. The median length of informed consent form was 20 pages (range: 8-28). A detailed estimation of the frequency or intensity of risks (range: 3-8 pages) was provided. The average reading level of the informed consent forms was high (Flesch-Kincaid Grade Level of 9.8), which corresponds roughly to 10th-grade reading level. Less than 15% of all consent forms were written at the recommended eighth-grade reading level. A substantial number of forms did not report a potential risk to pregnant/lactating women (16.9%), mechanism of action of the investigational agent (34.8%), study schema (77.6%), a possibility of receiving sub-therapeutic dose (37%), or death (12.5%). Nearly one half of the forms (49.1%) stated clearly that individual participants may not benefit. CONCLUSION: Overall, these informed consent forms provided a detailed description of the trials in accordance to international guidelines. However, there remains room for improvement, particularly in areas of readability and document length. PMID- 25135908 TI - Season and outdoor temperature in relation to detection and control of hypertension in a large rural Chinese population. AB - BACKGROUND: In many Western populations, blood pressure varies moderately with season and outdoor temperature. Relatively little is known about effects of seasonal changes in blood pressure on the detection and control of hypertension in general populations, especially in low- and middle-income countries. METHODS: We analysed cross-sectional data of 57 375 (42% men) participants aged 30-79 (mean 52.3) years who were enrolled during 2004-08, as part of the China Kadoorie Biobank, from a rural county in the south-east costal Zhejiang Province. Analyses related daily mean outdoor temperature, obtained from local Meteorological Bureau, to mean systolic (SBP) and diastolic blood pressure (DBP), rate of newly detected hypertension and, among those with self-reported physician-diagnosed hypertension, rate of adequate blood pressure control, using multiple linear and logistic regression models. RESULTS: The overall mean blood pressure was 135.9 mmHg for SBP and 80.5 mmHg for DBP. Daily outdoor temperature ranged between -2.9 and 33.7 degrees C, with July being the hottest month (mean 29.4 degrees C) and January the coldest (mean 4.0 degrees C). Comparing January (the coldest month) with July (the warmest), the differences in the adjusted SBP/DBP were 19.2/7.7 mmHg. Each 10 degrees C lower ambient temperature was associated with 6.9/2.9 mmHg higher SBP/DBP,14.1% higher prevalence of newly detected hypertension and, among those with pre-diagnosed hypertension, 13.0% lower hypertension control rate. CONCLUSION: In rural China, lower outdoor temperature is strongly associated with higher mean blood pressure and hypertension prevalence as well as poorer hypertension control, and should be considered when conducting population based hypertension surveys and providing treatment for hypertensive patients. PMID- 25135911 TI - Ocular pulsations due to posttraumatic compromise of the orbital roof. PMID- 25135912 TI - Spice, pot, and stroke. PMID- 25135913 TI - Ischemic stroke after use of the synthetic marijuana "spice". PMID- 25135916 TI - Clinical reasoning: a 42-year-old man who developed blurred vision and dropped his iPod while jogging. PMID- 25135917 TI - Teaching NeuroImages: recurrence of a sural intraneural ganglion cyst after sural nerve resection. PMID- 25135919 TI - Fix seniors' care first, says CMA president-elect. PMID- 25135920 TI - Controversy over doctors' right to say "no". PMID- 25135922 TI - E-cigarette ban proposed in Toronto. PMID- 25135924 TI - Dextromethorphan abuse. PMID- 25135921 TI - Assessment and management of resistant hypertension. PMID- 25135925 TI - Diabetes in an older woman living in a long-term care residence. PMID- 25135926 TI - Good health requires a healthy mouth: improving the oral health of Canada's seniors. PMID- 25135928 TI - Tracking brain injury and disability. PMID- 25135927 TI - Association of a quality improvement program with neonatal outcomes in extremely preterm infants: a prospective cohort study. AB - BACKGROUND: We previously demonstrated improvement in bronchopulmonary dysplasia and nosocomial infection among preterm infants at 12 neonatal units using the Evidence-based Practice for Improving Quality (EPIQ). In the current study, we assessed the association of Canada-wide implementation of EPIQ with mortality and morbidity among preterm infants less than 29 weeks gestational age. METHODS: This prospective cohort study included 6026 infants admitted to 25 Canadian units between 2008 and 2012 (baseline year, n = 1422; year 1, n = 1611; year 2, n = 1508; year 3, n = 1485). Following a 1-year baseline period and 6 months of training and planning, EPIQ was implemented over 3 years. Our primary outcome was a composite of neonatal mortality and any of bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity, necrotizing enterocolitis and nosocomial infection. We compared outcomes for baseline and year 3 using multivariable analyses. RESULTS: In adjusted analyses comparing baseline with year 3, the composite outcome (70% v. 65%; adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.51 to 0.79), severe retinopathy (17% v. 13%; OR 0.60, 95% CI 0.45 to 0.79), necrotizing enterocolitis (10% v. 8%; OR 0.73, 95% CI 0.52 to 0.98) and nosocomial infections (32% v. 24%; OR 0.63, 95% CI 0.48 to 0.82) were significantly reduced. The composite outcome was lower among infants born at 26 to 28 weeks gestation (62% v. 52%; OR 0.62, 95% CI 0.49 to 0.78) but not among infants born at less than 26 weeks gestational age (90% v. 88%; OR 0.73, 95% CI 0.44 to 1.20). INTERPRETATION: EPIQ methodology was generalizable within Canada and was associated with significantly lower likelihood of the composite outcome, severe retinopathy, necrotizing enterocolitis and nosocomial infections. Infants born at 26 to 28 weeks gestational age benefited the most. PMID- 25135929 TI - CMA wants seniors' care on federal agenda. PMID- 25135930 TI - Heidi McBride: mitochondria are well connected. PMID- 25135931 TI - A new piece in the kinetochore jigsaw puzzle. AB - In eukaryotic cell division, the kinetochore mediates chromosome attachment to spindle microtubules and acts as a scaffold for signaling pathways, ensuring the accuracy of chromosome segregation. The architecture of the kinetochore underlies its function in mitosis. In this issue, Hornung et al. (2014. J. Cell Biol. http://dx.doi.org/201403081) identify an unexpected linkage between the inner and outer regions of the kinetochore in budding yeast that suggests a new model for the construction of this interface. PMID- 25135933 TI - cPKC regulates interphase nuclear size during Xenopus development. AB - Dramatic changes in cell and nuclear size occur during development and differentiation, and aberrant nuclear size is associated with many disease states. However, the mechanisms that regulate nuclear size are largely unknown. A robust system for investigating nuclear size is early Xenopus laevis development, during which reductions in nuclear size occur without changes in DNA content. To identify cellular factors that regulate nuclear size during development, we developed a novel nuclear resizing assay wherein nuclei assembled in Xenopus egg extract become smaller in the presence of cytoplasmic interphase extract isolated from post-gastrula Xenopus embryos. We show that nuclear shrinkage depends on conventional protein kinase C (cPKC). Increased nuclear cPKC localization and activity and decreased nuclear association of lamins mediate nuclear size reductions during development, and manipulating cPKC activity in vivo during interphase alters nuclear size in the embryo. We propose a model of steady-state nuclear size regulation whereby nuclear expansion is balanced by an active cPKC dependent mechanism that reduces nuclear size. PMID- 25135932 TI - The tubulin code: molecular components, readout mechanisms, and functions. AB - Microtubules are cytoskeletal filaments that are dynamically assembled from alpha/beta-tubulin heterodimers. The primary sequence and structure of the tubulin proteins and, consequently, the properties and architecture of microtubules are highly conserved in eukaryotes. Despite this conservation, tubulin is subject to heterogeneity that is generated in two ways: by the expression of different tubulin isotypes and by posttranslational modifications (PTMs). Identifying the mechanisms that generate and control tubulin heterogeneity and how this heterogeneity affects microtubule function are long standing goals in the field. Recent work on tubulin PTMs has shed light on how these modifications could contribute to a "tubulin code" that coordinates the complex functions of microtubules in cells. PMID- 25135935 TI - Oxidoreductase activity is necessary for N-glycosylation of cysteine-proximal acceptor sites in glycoproteins. AB - Stabilization of protein tertiary structure by disulfides can interfere with glycosylation of acceptor sites (NXT/S) in nascent polypeptides. Here, we show that MagT1, an ER-localized thioredoxin homologue, is a subunit of the STT3B isoform of the oligosaccharyltransferase (OST). The lumenally oriented active site CVVC motif in MagT1 is required for glycosylation of STT3B-dependent acceptor sites including those that are closely bracketed by disulfides or contain cysteine as the internal residue (NCT/S). The MagT1- and STT3B-dependent glycosylation of cysteine-proximal acceptor sites can be reduced by eliminating cysteine residues. The predominant form of MagT1 in vivo is oxidized, which is consistent with transient formation of mixed disulfides between MagT1 and a glycoprotein substrate to facilitate access of STT3B to unmodified acceptor sites. Cotranslational N-glycosylation by the STT3A isoform of the OST, which lacks MagT1, allows efficient modification of acceptor sites in cysteine-rich protein domains before disulfide bond formation. Thus, mammalian cells use two mechanisms to achieve N-glycosylation of cysteine proximal acceptor sites. PMID- 25135937 TI - Pre-placement screening for tuberculosis in healthcare workers. AB - BACKGROUND: Healthcare workers (HCWs) are at occupational risk of contracting and transmitting tuberculosis (TB). Despite national guidance, the optimal process for the pre-placement screening of new entrant HCWs for TB in the UK is not certain, nor the appropriateness of using a one-step interferon gamma release assay (IGRA) screening programme. AIMS: To assess the potential for an IGRA-only TB screening programme for new entrant HCWs, and identify cost savings achieved through this process. METHODS: We conducted a retrospective analysis of IGRA and tuberculin skin tests (TST) within our occupational health service over a 3-year period. HCWs with markedly discordant test results (IGRA negative, TST positive) were followed up to determine whether they developed active TB. We also estimated the yearly cost savings if the existing two-step process was replaced with an IGRA-only programme. RESULTS: Totally, 96/1258 (8%) HCWs had positive IGRA results; 788 TSTs were performed for newly screened IGRA-negative HCWs without Bacille Calmette-Guerin scars, among which 597 (76%) tested negative (TST <6 mm). None of the 10 individuals with grossly discordant test results (TST >15 mm) developed active TB during the study period. We calculated savings of L20,453 if the two-step process was replaced with an IGRA-only programme. CONCLUSIONS: The absence of disease progression in individuals with markedly discordant results in this study suggest that an IGRA-only screening programme for new HCWs in the UK is feasible, and may be safe although our follow-up period was insufficient. Our results also suggest that substantial cost savings can be made by using this programme. PMID- 25135934 TI - A cooperative mechanism drives budding yeast kinetochore assembly downstream of CENP-A. AB - Kinetochores are megadalton-sized protein complexes that mediate chromosome microtubule interactions in eukaryotes. How kinetochore assembly is triggered specifically on centromeric chromatin is poorly understood. Here we use biochemical reconstitution experiments alongside genetic and structural analysis to delineate the contributions of centromere-associated proteins to kinetochore assembly in yeast. We show that the conserved kinetochore subunits Ame1(CENP-U) and Okp1(CENP-Q) form a DNA-binding complex that associates with the microtubule binding KMN network via a short Mtw1 recruitment motif in the N terminus of Ame1. Point mutations in the Ame1 motif disrupt kinetochore function by preventing KMN assembly on chromatin. Ame1-Okp1 directly associates with the centromere protein C (CENP-C) homologue Mif2 to form a cooperative binding platform for outer kinetochore assembly. Our results indicate that the key assembly steps, CENP-A recognition and outer kinetochore recruitment, are executed through different yeast constitutive centromere-associated network subunits. This two-step mechanism may protect against inappropriate kinetochore assembly similar to rate limiting nucleation steps used by cytoskeletal polymers. PMID- 25135938 TI - A survey of sitting time among UK employees. AB - BACKGROUND: Sedentary behaviour is a known risk factor for a wide range of chronic diseases. This major health risk is likely to increase given the increasingly sedentary nature of work. AIMS: To investigate the prevalence of sedentary behaviour in a sample of UK working-aged adults, across a range of employment sectors. METHODS: A cross-sectional survey conducted with organizations throughout the UK in the education, government administration, retail, telecommunications and service industry sectors. The questionnaire examined employee and organizational information, self-reported domain-specific sitting time, sleep and physical activity. RESULTS: A total of 1141 employees completed the questionnaire, of which 504 completed all aspects of the Domain Specific Sitting Time Questionnaire for work day sitting. Work time sitting accounted for more than half of the total daily sitting time on a work day (54%). Significantly more time was reported sitting on a work day than time reported sleeping (P < 0.001). Males spent more time sitting at work and using a personal computer at home compared with females. Workers in the telecommunications industry had the highest sitting times. There were significant positive associations between sitting time and body mass index. CONCLUSIONS: There is a pressing need for future workplace health interventions to reduce employee sitting times. PMID- 25135936 TI - High density and ligand affinity confer ultrasensitive signal detection by a guanylyl cyclase chemoreceptor. AB - Guanylyl cyclases (GCs), which synthesize the messenger cyclic guanosine 3',5' monophosphate, control several sensory functions, such as phototransduction, chemosensation, and thermosensation, in many species from worms to mammals. The GC chemoreceptor in sea urchin sperm can decode chemoattractant concentrations with single-molecule sensitivity. The molecular and cellular underpinnings of such ultrasensitivity are not known for any eukaryotic chemoreceptor. In this paper, we show that an exquisitely high density of 3 * 10(5) GC chemoreceptors and subnanomolar ligand affinity provide a high ligand-capture efficacy and render sperm perfect absorbers. The GC activity is terminated within 150 ms by dephosphorylation steps of the receptor, which provides a means for precise control of the GC lifetime and which reduces "molecule noise." Compared with other ultrasensitive sensory systems, the 10-fold signal amplification by the GC receptor is surprisingly low. The hallmarks of this signaling mechanism provide a blueprint for chemical sensing in small compartments, such as olfactory cilia, insect antennae, or even synaptic boutons. PMID- 25135939 TI - Identification of a new stem cell population that generates Drosophila flight muscles. AB - How myoblast populations are regulated for the formation of muscles of different sizes is an essentially unanswered question. The large flight muscles of Drosophila develop from adult muscle progenitor (AMP) cells set-aside embryonically. The thoracic segments are all allotted the same small AMP number, while those associated with the wing-disc proliferate extensively to give rise to over 2500 myoblasts. An initial amplification occurs through symmetric divisions and is followed by a switch to asymmetric divisions in which the AMPs self-renew and generate post-mitotic myoblasts. Notch signaling controls the initial amplification of AMPs, while the switch to asymmetric division additionally requires Wingless, which regulates Numb expression in the AMP lineage. In both cases, the epidermal tissue of the wing imaginal disc acts as a niche expressing the ligands Serrate and Wingless. The disc-associated AMPs are a novel muscle stem cell population that orchestrates the early phases of adult flight muscle development. PMID- 25135941 TI - ExaBayes: massively parallel bayesian tree inference for the whole-genome era. AB - Modern sequencing technology now allows biologists to collect the entirety of molecular evidence for reconstructing evolutionary trees. We introduce a novel, user-friendly software package engineered for conducting state-of-the-art Bayesian tree inferences on data sets of arbitrary size. Our software introduces a nonblocking parallelization of Metropolis-coupled chains, modifications for efficient analyses of data sets comprising thousands of partitions and memory saving techniques. We report on first experiences with Bayesian inferences at the whole-genome level using the SuperMUC supercomputer and simulated data. PMID- 25135940 TI - mRNA-programmed translation pauses in the targeting of E. coli membrane proteins. AB - In all living organisms, ribosomes translating membrane proteins are targeted to membrane translocons early in translation, by the ubiquitous signal recognition particle (SRP) system. In eukaryotes, the SRP Alu domain arrests translation elongation of membrane proteins until targeting is complete. Curiously, however, the Alu domain is lacking in most eubacteria. In this study, by analyzing genome wide data on translation rates, we identified a potential compensatory mechanism in E. coli that serves to slow down the translation during membrane protein targeting. The underlying mechanism is likely programmed into the coding sequence, where Shine-Dalgarno-like elements trigger elongation pauses at strategic positions during the early stages of translation. We provide experimental evidence that slow translation during targeting and improves membrane protein production fidelity, as it correlates with better folding of overexpressed membrane proteins. Thus, slow elongation is important for membrane protein targeting in E. coli, which utilizes mechanisms different from the eukaryotic one to control the translation speed. PMID- 25135943 TI - Adaptive functional diversification of lysozyme in insectivorous bats. AB - The role of gene duplication in generating new genes and novel functions is well recognized and is exemplified by the digestion-related protein lysozyme. In ruminants, duplicated chicken-type lysozymes facilitate the degradation of symbiotic bacteria in the foregut. Chicken-type lysozyme has also been reported to show chitinase-like activity, yet no study has examined the molecular evolution of lysozymes in species that specialize on eating insects. Insectivorous bats number over 900 species, and lysozyme expression in the mouths of some of these species is associated with the ingestion of insect cuticle, suggesting a chitinase role. Here, we show that chicken-type lysozyme has undergone multiple duplication events in a major family of insect-eating bats (Vespertilionidae) and that new duplicates have undergone molecular adaptation. Examination of duplicates from two insectivorous bats-Pipistrellus abramus and Scotophilus kuhlii-indicated that the new copy was highly expressed in the tongue, whereas the other one was less tissue-specific. Functional assays applied to pipistrelle lysozymes confirmed that, of the two copies, the tongue duplicate was more efficient at breaking down glycol chitin, a chitin derivative. These results suggest that the evolution of lysozymes in vespertilionid bats has likely been driven in part by natural selection for insectivory. PMID- 25135944 TI - Independent birth of a novel TRIMCyp in Tupaia belangeri with a divergent function from its paralog TRIM5. AB - The origin of novel genes and their evolutionary fates are long-standing questions in evolutionary biology. These questions become more complicated for genes conserved across various lineages, such as TRIM5, an antiretroviral restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 has been subjected to numerous pathogenic challenges and undergone dynamic evolution, making it an excellent example for studying gene diversification. Previous studies among several species showed that TRIM5 gained genetic and functional novelty in a lineage-specific manner, either through gene duplication or a cyclophilin A retrotransposing into the TRIM5 locus, creating the gene fusion known as TRIM5-Cyclophilin A (TRIMCyp). To date, the general pattern of TRIM5 across the mammalian lineage remains elusive. In this study, we surveyed 36 mammalian genomes to verify a potentially novel TRIM5 pattern that uniquely seems to have occurred in tree shrews (Tupaia belangeri), and found that both gene duplication and retrotransposition worked jointly to form a specific TRIM5/TRIMCyp cluster not found among other mammals. Evolutionary analyses showed that tree shrew TRIMCyp (tsTRIMCyp) originated independently in comparison with previously reported TRIMCyps and underwent strong positive selection, whereas no signal of positive selection was detected for other tree shrew TRIM5 (tsTRIM5) genes. Functional assay results suggest a functional divergence between tsTRIMCyp and its closest paralog TRIM5-4, likely reflecting different fates under diverse evolutionary forces. These findings present a rare example of novel gene origination resulting from a combination of gene duplication, retrotransposition, and exon shuffling processes, providing a new paradigm to study genetic innovations and evolutionary fates of duplicated genes. PMID- 25135942 TI - Integrating evolutionary and functional tests of adaptive hypotheses: a case study of altitudinal differentiation in hemoglobin function in an Andean Sparrow, Zonotrichia capensis. AB - In air-breathing vertebrates, the physiologically optimal blood-O2 affinity is jointly determined by the prevailing partial pressure of atmospheric O2, the efficacy of pulmonary O2 transfer, and internal metabolic demands. Consequently, genetic variation in the oxygenation properties of hemoglobin (Hb) may be subject to spatially varying selection in species with broad elevational distributions. Here we report the results of a combined functional and evolutionary analysis of Hb polymorphism in the rufous-collared sparrow (Zonotrichia capensis), a species that is continuously distributed across a steep elevational gradient on the Pacific slope of the Peruvian Andes. We integrated a population genomic analysis that included all postnatally expressed Hb genes with functional studies of naturally occurring Hb variants, as well as recombinant Hb (rHb) mutants that were engineered through site-directed mutagenesis. We identified three clinally varying amino acid polymorphisms: Two in the alpha(A)-globin gene, which encodes the alpha-chain subunits of the major HbA isoform, and one in the alpha(D)-globin gene, which encodes the alpha-chain subunits of the minor HbD isoform. We then constructed and experimentally tested single- and double-mutant rHbs representing each of the alternative alpha(A)-globin genotypes that predominate at different elevations. Although the locus-specific patterns of altitudinal differentiation suggested a history of spatially varying selection acting on Hb polymorphism, the experimental tests demonstrated that the observed amino acid mutations have no discernible effect on respiratory properties of the HbA or HbD isoforms. These results highlight the importance of experimentally validating the hypothesized effects of genetic changes in protein function to avoid the pitfalls of adaptive storytelling. PMID- 25135945 TI - Detecting recent positive selection with high accuracy and reliability by conditional coalescent tree. AB - Studies of natural selection, followed by functional validation, are shedding light on understanding of genetic mechanisms underlying human evolution and adaptation. Classic methods for detecting selection, such as the integrated haplotype score (iHS) and Fay and Wu's H statistic, are useful for candidate gene searching underlying positive selection. These methods, however, have limited capability to localize causal variants in selection target regions. In this study, we developed a novel method based on conditional coalescent tree to detect recent positive selection by counting unbalanced mutations on coalescent gene genealogies. Extensive simulation studies revealed that our method is more robust than many other approaches against biases due to various demographic effects, including population bottleneck, expansion, or stratification, while not sacrificing its power. Furthermore, our method demonstrated its superiority in localizing causal variants from massive linked genetic variants. The rate of successful localization was about 20-40% higher than that of other state-of-the art methods on simulated data sets. On empirical data, validated functional causal variants of four well-known positive selected genes were all successfully localized by our method, such as ADH1B, MCM6, APOL1, and HBB. Finally, the computational efficiency of this new method was much higher than that of iHS implementations, that is, 24-66 times faster than the REHH package, and more than 10,000 times faster than the original iHS implementation. These magnitudes make our method suitable for applying on large sequencing data sets. Software can be downloaded from https://github.com/wavefancy/scct. PMID- 25135946 TI - Evidence for a gene involved in multiple and diverse rearrangements in the Drosophila genus. AB - In Drosophila, chromosomes have been extensively reorganized during evolution, with most rearrangements affecting the gene order in chromosomal elements but not their gene content. The level of reorganization and the evidence for breakpoint reuse vary both between and within elements. The subito gene stands out as a gene involved in multiple rearrangements both because of its active single-gene transposition and because it is the nearest gene to diverse rearrangements breakpoints. Indeed, subito has undergone three single-gene transpositions and it is the nearest gene to the breakpoints of other single-gene transpositions and of two chromosomal inversions. Given that subito is involved in meiosis and therefore active in the female germ line, the high number of nearby fixed breakages might be related among others to the presumed high accessibility of the subito region to the machinery associated with double-strand breaks repair. A second important contributor would be the reduced and simple regulatory region of subito, which would imply that a fraction of the rearrangements originating from subito nearby breakages would have not affected either its pattern or timing of expression and would have, thus, not resulted in reduced fitness. PMID- 25135947 TI - Crossing-over in a hypervariable species preferentially occurs in regions of high local similarity. AB - Recombination between double-stranded DNA molecules is a key genetic process which occurs in a wide variety of organisms. Usually, crossing-over (CO) occurs during meiosis between genotypes with 98.0-99.9% sequence identity, because within-population nucleotide diversity only rarely exceeds 2%. However, some species are hypervariable and it is unclear how CO can occur between genotypes with less than 90% sequence identity. Here, we study CO in Schizophyllum commune, a hypervariable cosmopolitan basidiomycete mushroom, a frequently encountered decayer of woody substrates. We crossed two haploid individuals, from the United States and from Russia, and obtained genome sequences for their 17 offspring. The average genetic distance between the parents was 14%, making it possible to study CO at very high resolution. We found reduced levels of linkage disequilibrium between loci flanking the CO sites indicating that they are mostly confined to hotspots of recombination. Furthermore, CO events preferentially occurred in regions under stronger negative selection, in particular within exons that showed reduced levels of nucleotide diversity. Apparently, in hypervariable species CO must avoid regions of higher divergence between the recombining genomes due to limitations imposed by the mismatch repair system, with regions under strong negative selection providing the opportunity for recombination. These patterns are opposite to those observed in a number of less variable species indicating that population genomics of hypervariable species may reveal novel biological phenomena. PMID- 25135949 TI - Eukaryotic penelope-like retroelements encode hammerhead ribozyme motifs. AB - Small self-cleaving RNAs, such as the paradigmatic Hammerhead ribozyme (HHR), have been recently found widespread in DNA genomes across all kingdoms of life. In this work, we found that new HHR variants are preserved in the ancient family of Penelope-like elements (PLEs), a group of eukaryotic retrotransposons regarded as exceptional for encoding telomerase-like retrotranscriptases and spliceosomal introns. Our bioinformatic analysis revealed not only the presence of minimalist HHRs in the two flanking repeats of PLEs but also their massive and widespread occurrence in metazoan genomes. The architecture of these ribozymes indicates that they may work as dimers, although their low self-cleavage activity in vitro suggests the requirement of other factors in vivo. In plants, however, PLEs show canonical HHRs, whereas fungi and protist PLEs encode ribozyme variants with a stable active conformation as monomers. Overall, our data confirm the connection of self-cleaving RNAs with eukaryotic retroelements and unveil these motifs as a significant fraction of the encoded information in eukaryotic genomes. PMID- 25135950 TI - Importance of carcinoma-associated fibroblast-derived proteins in clinical oncology. AB - Carcinoma-associated fibroblast (CAF) as prominent cell type of the tumour microenvironment has complex interaction with both the cancer cells and other non neoplastic surrounding cells. The CAF-derived regulators and extracellular matrix proteins can support cancer progression by providing a protective microenvironment for the cancer cells via reduction of chemotherapy sensitivity. On the other hand, these proteins may act as powerful prognostic markers as well as potential targets of anticancer therapy. In this review, we summarise the clinical importance of the major CAF-derived signals influencing tumour behaviour and determining the outcome of chemotherapy. PMID- 25135948 TI - Parallel evolution of tetrodotoxin resistance in three voltage-gated sodium channel genes in the garter snake Thamnophis sirtalis. AB - Members of a gene family expressed in a single species often experience common selection pressures. Consequently, the molecular basis of complex adaptations may be expected to involve parallel evolutionary changes in multiple paralogs. Here, we use bacterial artificial chromosome library scans to investigate the evolution of the voltage-gated sodium channel (Nav) family in the garter snake Thamnophis sirtalis, a predator of highly toxic Taricha newts. Newts possess tetrodotoxin (TTX), which blocks Nav's, arresting action potentials in nerves and muscle. Some Thamnophis populations have evolved resistance to extremely high levels of TTX. Previous work has identified amino acid sites in the skeletal muscle sodium channel Nav1.4 that confer resistance to TTX and vary across populations. We identify parallel evolution of TTX resistance in two additional Nav paralogs, Nav1.6 and 1.7, which are known to be expressed in the peripheral nervous system and should thus be exposed to ingested TTX. Each paralog contains at least one TTX-resistant substitution identical to a substitution previously identified in Nav1.4. These sites are fixed across populations, suggesting that the resistant peripheral nerves antedate resistant muscle. In contrast, three sodium channels expressed solely in the central nervous system (Nav1.1-1.3) showed no evidence of TTX resistance, consistent with protection from toxins by the blood-brain barrier. We also report the exon-intron structure of six Nav paralogs, the first such analysis for snake genes. Our results demonstrate that the molecular basis of adaptation may be both repeatable across members of a gene family and predictable based on functional considerations. PMID- 25135952 TI - The most important application of science: As scientists have to justify research funding with potential social benefits, they may well add education to the list. PMID- 25135951 TI - Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes. AB - Thermogenesis in brown adipocytes, conferred by mitochondrial uncoupling protein 1 (UCP1), is receiving great attention because metabolically active brown adipose tissue may protect humans from metabolic diseases. In particular, the thermogenic function of brown-like adipocytes in white adipose tissue, known as brite (or beige) adipocytes, is currently of prime interest. A valid procedure to quantify the specific contribution of UCP1 to thermogenesis is thus of vital importance. Adrenergic stimulation of lipolysis is a common way to activate UCP1. We here report, however, that in this frequently applied setup, taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured brown and brite adipocytes. By the application of these findings, we demonstrate that UCP1 is functionally thermogenic in intact brite adipocytes and adrenergic UCP1 activation is largely dependent on adipose triglyceride lipase (ATGL) rather than hormone sensitive lipase (HSL). PMID- 25135954 TI - Has enough evidence accumulated to consider CPAP a first-line standard of care in developing countries? PMID- 25135953 TI - Is the role as gatekeeper still feasible? A survey among Dutch general practitioners. AB - INTRODUCTION: In the 2012 International Health Policy Survey by the Commonwealth Fund, 57% of Dutch GPs indicated that Dutch patients receive too much health care. This is an unexpected finding, given the clear gatekeeper role of Dutch GPs and recent efforts strengthening this role. OBJECTIVES: The study aims to explore where perceived overuse of care prevails and to identify factors associated with too much care at the entry point of Dutch health care. METHOD: An American survey exploring perceptions of the amount of care among primary care providers was modified for relevance to the Dutch health system. We further included additional factors possibly related to overuse based on 12 interviews with Dutch GPs. The survey was sent to a random sample of 600 GPs. RESULTS: Dutch GPs (N = 157; response rate 26.2%) indicated that patients receive (much) too much care in general hospitals, primary care, GP cooperatives as well as private clinics. The Dutch responding GPs showed a relatively demand-satisfying attitude, which contributed to the delivery of too much care, often leading to deviation from guidelines and professional norms. The increasing availability of diagnostic facilities was identified as an additional factor contributing to the provision of unnecessary care. Finally, funding gaps between primary care and hospitals impede cooperation and coordination, provoking unnecessary care. CONCLUSION: Our results--most notably regarding the demand-satisfying attitude of responding GPs- call into question the classical view of the guidance and gatekeeper role of GPs in the Dutch health care system. PMID- 25135955 TI - Prematurity and programming of cardiovascular disease risk: a future challenge for public health? AB - There is substantial epidemiological evidence linking low birth weight with adult cardiometabolic disease risk factors. This has led to the concept of 'early life programming' or the 'developmental origins of disease' which proposes that exposure to adverse conditions during critical stages of early development results in compensatory mechanisms predicted to aid survival. There is growing evidence that preterm infants, many of whom are of low birth weight, are also at increased risk of adult cardiometabolic disease. In this article, we provide a broad overview of the evidence linking preterm birth and cardiovascular disease risk and discuss potential consequences for public health. PMID- 25135956 TI - H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress. AB - The selectivity of transcriptional responses to extracellular cues is reflected by the deposition of stimulus-specific chromatin marks. Although histone H3 phosphorylation is a target of numerous signaling pathways, its role in transcriptional regulation remains poorly understood. Here, for the first time, we report a genome-wide analysis of H3S28 phosphorylation in a mammalian system in the context of stress signaling. We found that this mark targets as many as 50% of all stress-induced genes, underlining its importance in signal-induced transcription. By combining ChIP-seq, RNA-seq, and mass spectrometry we identified the factors involved in the biological interpretation of this histone modification. We found that MSK1/2-mediated phosphorylation of H3S28 at stress responsive promoters contributes to the dissociation of HDAC corepressor complexes and thereby to enhanced local histone acetylation and subsequent transcriptional activation of stress-induced genes. Our data reveal a novel function of the H3S28ph mark in the activation of mammalian genes in response to MAP kinase pathway activation. PMID- 25135959 TI - Innovative practice editorial. PMID- 25135957 TI - The landscape of human STR variation. AB - Short tandem repeats are among the most polymorphic loci in the human genome. These loci play a role in the etiology of a range of genetic diseases and have been frequently utilized in forensics, population genetics, and genetic genealogy. Despite this plethora of applications, little is known about the variation of most STRs in the human population. Here, we report the largest-scale analysis of human STR variation to date. We collected information for nearly 700,000 STR loci across more than 1000 individuals in Phase 1 of the 1000 Genomes Project. Extensive quality controls show that reliable allelic spectra can be obtained for close to 90% of the STR loci in the genome. We utilize this call set to analyze determinants of STR variation, assess the human reference genome's representation of STR alleles, find STR loci with common loss-of-function alleles, and obtain initial estimates of the linkage disequilibrium between STRs and common SNPs. Overall, these analyses further elucidate the scale of genetic variation beyond classical point mutations. PMID- 25135958 TI - RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas. AB - Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs. PMID- 25135962 TI - Introduction. PMID- 25135963 TI - Analysis of the RNA content of the exosomes derived from blood serum and urine and its potential as biomarkers. AB - Exosomes are tiny vesicles (30-150 nm) constantly secreted by all healthy and abnormal cells, and found in abundance in all body fluids. These vesicles, loaded with unique RNA and protein cargo, have a wide range of biological functions, including cell-to-cell communication and signalling. As such, exosomes hold tremendous potential as biomarkers and could lead to the development of minimally invasive diagnostics and next generation therapies within the next few years. Here, we describe the strategies for isolation of exosomes from human blood serum and urine, characterization of their RNA cargo by sequencing, and present the initial data on exosome labelling and uptake tracing in a cell culture model. The value of exosomes for clinical applications is discussed with an emphasis on their potential for diagnosing and treating neurodegenerative diseases and brain cancer. PMID- 25135964 TI - Exosome platform for diagnosis and monitoring of traumatic brain injury. AB - We have previously demonstrated the release of membranous structures by cells into their extracellular environment, which are termed exosomes, microvesicles or extracellular vesicles depending on specific characteristics, including size, composition and biogenesis pathway. With activation, injury, stress, transformation or infection, cells express proteins and RNAs associated with the cellular responses to these events. The exosomes released by these cells can exhibit an array of proteins, lipids and nucleic acids linked to these physiologic events. This review focuses on exosomes associated with traumatic brain injury, which may be both diagnostic and a causative factor in the progression of the injury. Based on current data, exosomes play essential roles as conveyers of intercellular communication and mediators of many of the pathological conditions associated with development, progression and therapeutic failures and cellular stress in a variety of pathologic conditions. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodelling, signal pathway activation through growth factor/receptor transfer, chemoresistance, immunologic activation and genetic exchange. These circulating exosomes not only represent a central mediator of the pro inflammatory microenvironment linked with secondary brain injury, but their presence in the peripheral circulation may serve as a surrogate for biopsies, enabling real-time diagnosis and monitoring of neurodegenerative progression. PMID- 25135966 TI - Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of wiring transmission add a new dimension to brain neuro-glial networks. AB - Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (WT; point-to-point communication via private channels, e.g. synaptic transmission) and volume transmission (VT; communication in the extracellular fluid and in the cerebrospinal fluid). Volume and synaptic transmission become integrated because their chemical signals activate different types of interacting receptors in heteroreceptor complexes located synaptically and extrasynaptically in the plasma membrane. In VT, we focus on the role of the extracellular-vesicle type of VT, and in WT, on the potential role of the tunnelling-nanotube (TNT) type of WT. The so-called exosomes appear to be the major vesicular carrier for intercellular communication but the larger microvesicles also participate. Extracellular vesicles are released from cultured cortical neurons and different types of glial cells and modulate the signalling of the neuronal-glial networks of the CNS. This type of VT has pathological relevance, and epigenetic mechanisms may participate in the modulation of extracellular-vesicle-mediated VT. Gerdes and co-workers proposed the existence of a novel type of WT based on TNTs, which are straight transcellular channels leading to the formation in vitro of syncytial cellular networks found also in neuronal and glial cultures. PMID- 25135965 TI - The RNA-centred view of the synapse: non-coding RNAs and synaptic plasticity. AB - If mRNAs were the only RNAs made by a neuron, there would be a simple mapping of mRNAs to proteins. However, microRNAs and other non-coding RNAs (ncRNAs; endo siRNAs, piRNAs, BC1, BC200, antisense and long ncRNAs, repeat-related transcripts, etc.) regulate mRNAs via effects on protein translation as well as transcriptional and epigenetic mechanisms. Not only are genes ON or OFF, but their ability to be translated can be turned ON or OFF at the level of synapses, supporting an enormous increase in information capacity. Here, I review evidence that ncRNAs are expressed pervasively within dendrites in mammalian brain; that some are activity-dependent and highly enriched near synapses; and that synaptic ncRNAs participate in plasticity responses including learning and memory. Ultimately, ncRNAs can be viewed as the post-it notes of the neuron. They have no literal meaning of their own, but derive their functions from where (and to what) they are stuck. This may explain, in part, why ncRNAs differ so dramatically from protein-coding genes, both in terms of the usual indicators of functionality and in terms of evolutionary constraints. ncRNAs do not appear to be direct mediators of synaptic transmission in the manner of neurotransmitters or receptors, yet they orchestrate synaptic plasticity-and may drive species-specific changes in cognition. PMID- 25135967 TI - An evolving view of epigenetic complexity in the brain. AB - Recent scientific advances have revolutionized our understanding of classical epigenetic mechanisms and the broader landscape of molecular interactions and cellular functions that are inextricably linked to these processes. Our current view of epigenetics includes an increasing appreciation for the dynamic nature of DNA methylation, active mechanisms for DNA demethylation, differential functions of 5-methylcytosine and its oxidized derivatives, the intricate regulatory logic of histone post-translational modifications, the incorporation of histone variants into chromatin, nucleosome occupancy and dynamics, and direct links between cellular signalling pathways and the actions of chromatin 'reader', 'writer' and 'eraser' molecules. We also have an increasing awareness of the seemingly ubiquitous roles played by diverse classes of selectively expressed non coding RNAs in transcriptional, post-transcriptional, post-translational and local and higher order chromatin modulatory processes. These perspectives are still evolving with novel insights continuing to emerge rapidly (e.g. those related to epigenetic regulation of mobile genetic elements, epigenetic mechanisms in mitochondria, roles in nuclear architecture and 'RNA epigenetics'). The precise functions of these epigenetic factors/phenomena are largely unknown. However, it is unequivocal that they serve as key mediators of brain complexity and flexibility, including neural development and aging, cellular differentiation, homeostasis, stress responses, and synaptic and neural network connectivity and plasticity. PMID- 25135969 TI - Long-term climbing fibre activity induces transcription of microRNAs in cerebellar Purkinje cells. AB - Synaptic activation of central neurons is often evoked by electrical stimulation leading to post-tetanic potentiation, long-term potentiation or long-term depression. Even a brief electrical tetanus can induce changes in as many as 100 proteins. Since climbing fibre activity is often associated with cerebellar behavioural plasticity, we used horizontal optokinetic stimulation (HOKS) to naturally increase synaptic input to floccular Purkinje cells in mice for hours, not minutes, and investigated how this activity influenced the transcription of microRNAs, small non-coding nucleotides that reduce transcripts of multiple, complementary mRNAs. A single microRNA can reduce the translation of as many as 30 proteins. HOKS evoked increases in 12 microRNA transcripts in floccular Purkinje cells. One of these microRNAs, miR335, increased 18-fold after 24 h of HOKS. After HOKS stopped, miR335 transcripts decayed with a time constant of approximately 2.5 h. HOKS evoked a 28-fold increase in pri-miR335 transcripts compared with an 18-fold increase in mature miR335 transcripts, confirming that climbing fibre-evoked increases in miR335 could be attributed to increases in transcription. We used three screens to identify potential mRNA targets for miR335 transcripts: (i) nucleotide complementarity, (ii) detection of increased mRNAs following microinjection of miR335 inhibitors into the cerebellum, and (iii) detection of decreased mRNAs following HOKS. Two genes, calbindin and 14-3 3-theta, passed these screens. Transfection of N2a cells with miR335 inhibitors or precursors inversely regulated 14-3-3-theta transcripts. Immunoprecipitation of 14-3-3-theta co-immunoprecipitated PKC-gamma and GABAAgamma2. Knockdown of either 14-3-3-theta or PKC-gamma decreased the serine phosphorylation of GABAAgamma2, suggesting that 14-3-3-theta and PKC-gamma under the control of miR335 homeostatically regulate the phosphorylation and insertion of GABAAgamma2 into the Purkinje cell post-synaptic membrane. PMID- 25135968 TI - The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease. AB - Long non-coding RNAs (lncRNAs) are transcripts with low protein-coding potential that represent a large proportion of the transcriptional output of the cell. Many lncRNAs exhibit features indicative of functionality including tissue-restricted expression, localization to distinct subcellular structures, regulated expression and evolutionary conservation. Some lncRNAs have been shown to associate with chromatin-modifying activities and transcription factors, suggesting that a common mode of action may be to guide protein complexes to target genomic loci. However, the functions (if any) of the vast majority of lncRNA transcripts are currently unknown, and the subject of investigation. Here, we consider the putative role(s) of lncRNAs in neurodevelopment and brain function with an emphasis on the epigenetic regulation of gene expression. Associations of lncRNAs with neurodevelopmental/neuropsychiatric disorders, neurodegeneration and brain cancers are also discussed. PMID- 25135970 TI - Systematic identification of 3'-UTR regulatory elements in activity-dependent mRNA stability in hippocampal neurons. AB - Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long-term memory storage. Activity-dependent, post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity in rat hippocampal neurons. In this study, we demonstrate rapid, post transcriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destabilized transcripts, identifies enrichment in sequence motifs corresponding to microRNA (miRNA)-binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further find that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory. PMID- 25135971 TI - Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal firing rate, signal transduction and gene regulation. AB - Exosomes are small membranous vesicles of endocytic origin that are released by almost every cell type. They exert versatile functions in intercellular communication important for many physiological and pathological processes. Recently, exosomes attracted interest with regard to their role in cell-cell communication in the nervous system. We have shown that exosomes released from oligodendrocytes upon stimulation with the neurotransmitter glutamate are internalized by neurons and enhance the neuronal stress tolerance. Here, we demonstrate that oligodendroglial exosomes also promote neuronal survival during oxygen-glucose deprivation, a model of cerebral ischaemia. We show the transfer from oligodendrocytes to neurons of superoxide dismutase and catalase, enzymes which are known to help cells to resist oxidative stress. Additionally, we identify various effects of oligodendroglial exosomes on neuronal physiology. Electrophysiological analysis using in vitro multi-electrode arrays revealed an increased firing rate of neurons exposed to oligodendroglial exosomes. Moreover, gene expression analysis and phosphorylation arrays uncovered differentially expressed genes and altered signal transduction pathways in neurons after exosome treatment. Our study thus provides new insight into the broad spectrum of action of oligodendroglial exosomes and their effects on neuronal physiology. The exchange of extracellular vesicles between neural cells may exhibit remarkable potential to impact brain performance. PMID- 25135972 TI - Epigenetic setting and reprogramming for neural cell fate determination and differentiation. AB - In the mammalian brain, epigenetic mechanisms are clearly involved in the regulation of self-renewal of neural stem cells and the derivation of their descendants, i.e. neurons, astrocytes and oligodendrocytes, according to the developmental timing and the microenvironment, the 'niche'. Interestingly, local epigenetic changes occur, concomitantly with genome-wide level changes, at a set of gene promoter regions for either down- or upregulation of the gene. In addition, intergenic regions also sensitize the availability of epigenetic modifiers, which affects gene expression through a relatively long-range chromatinic interaction with the transcription regulatory machineries including non-coding RNA (ncRNA) such as promoter-associated ncRNA and enhancer ncRNA. We show that such an epigenetic landscape in a neural cell is statically but flexibly formed together with a variable combination of generally and locally acting nuclear molecules including master transcription factors and cell-cycle regulators. We also discuss the possibility that revealing the epigenetic regulation by the local DNA-RNA-protein assemblies would promote methodological innovations, e.g. neural cell reprogramming, engineering and transplantation, to manipulate neuronal and glial cell fates for the purpose of medical use of these cells. PMID- 25135973 TI - DNA modifications in the mammalian brain. AB - DNA methylation is a crucial epigenetic mark in mammalian development, genomic imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA elements. DNA methylation in neurons has also been suggested to play important roles for mammalian neuronal functions, and learning and memory. In this review, we first summarize recent discoveries and fundamental principles of DNA modifications in the general epigenetics field. We then describe the profiles of different DNA modifications in the mammalian brain genome. Finally, we discuss roles of DNA modifications in mammalian brain development and function. PMID- 25135974 TI - The methylated-DNA binding protein MBD2 enhances NGFI-A (egr-1)-mediated transcriptional activation of the glucocorticoid receptor. AB - Variations in maternal care in the rat influence the epigenetic state and transcriptional activity of glucocorticoid receptor (GR) gene in the hippocampus. The mechanisms underlying this maternal effect remained to be defined, including the nature of the relevant maternally regulated intracellular signalling pathways. We show here that increased maternal licking/grooming (LG), which stably enhances hippocampal GR expression, paradoxically increases hippocampal expression of the methyl-CpG binding domain protein-2 (MBD2) and MBD2 binding to the exon 17 GR promoter. Knockdown experiments of MBD2 in hippocampal primary cell culture show that MBD2 is required for activation of exon 17 GR promoter. Ectopic co-expression of nerve growth factor-inducible protein A (NGFI-A) with MBD2 in HEK 293 cells with site-directed mutagenesis of the NGFI-A response element within the methylated exon 17 GR promoter supports the hypothesis that MBD2 collaborates with NGFI-A in binding and activation of this promoter. These data suggest a possible mechanism linking signalling pathways, which are activated by behavioural stimuli and activation of target genes. PMID- 25135975 TI - Regulation of histone H3K4 methylation in brain development and disease. AB - The growing list of mutations implicated in monogenic disorders of the developing brain includes at least seven genes (ARX, CUL4B, KDM5A, KDM5C, KMT2A, KMT2C, KMT2D) with loss-of-function mutations affecting proper regulation of histone H3 lysine 4 methylation, a chromatin mark which on a genome-wide scale is broadly associated with active gene expression, with its mono-, di- and trimethylated forms differentially enriched at promoter and enhancer and other regulatory sequences. In addition to these rare genetic syndromes, dysregulated H3K4 methylation could also play a role in the pathophysiology of some cases diagnosed with autism or schizophrenia, two conditions which on a genome-wide scale are associated with H3K4 methylation changes at hundreds of loci in a subject specific manner. Importantly, the reported alterations for some of the diseased brain specimens included a widespread broadening of H3K4 methylation profiles at gene promoters, a process that could be regulated by the UpSET(KMT2E/MLL5) histone deacetylase complex. Furthermore, preclinical studies identified maternal immune activation, parental care and monoaminergic drugs as environmental determinants for brain-specific H3K4 methylation. These novel insights into the epigenetic risk architectures of neurodevelopmental disease will be highly relevant for efforts aimed at improved prevention and treatment of autism and psychosis spectrum disorders. PMID- 25135976 TI - MicroRNAs and synaptic plasticity--a mutual relationship. AB - MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain- and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity. PMID- 25135977 TI - Extracellular vesicles as modulators of cell-to-cell communication in the healthy and diseased brain. AB - Homeostasis relies heavily on effective cell-to-cell communication. In the central nervous system (CNS), probably more so than in other organs, such communication is crucial to support and protect neurons especially during ageing, as well as to control inflammation, remove debris and infectious agents. Emerging evidence indicates that extracellular vesicles (EVs) including endosome-derived exosomes and fragments of the cellular plasma membrane play a key role in intercellular communication by transporting messenger RNA, microRNA (miRNA) and proteins. In neurodegenerative diseases, secreted vesicles not only remove misfolded proteins, but also transfer aggregated proteins and prions and are thus thought to perpetuate diseases by 'infecting' neighbouring cells with these pathogenic proteins. Conversely, in other CNS disorders signals from stressed cells may help control inflammation and inhibit degeneration. EVs may also reflect the status of the CNS and are present in the cerebrospinal fluid indicating that exosomes may act as biomarkers of disease. That extracellular RNA and in particular miRNA, can be transferred by EV also indicates that these vesicles could be used as carriers to specifically target the CNS to deliver immune modulatory drugs, neuroprotective agents and anti-cancer drugs. Here, we discuss the recent evidence indicating the potential role of exosomes in neurological disorders and how knowledge of their biology may enable a Trojan horse approach to deliver drugs into the CNS and treat neurodegenerative and other disorders of the CNS. PMID- 25135978 TI - MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development. AB - Neuronal connectivity and specificity rely upon precise coordinated deployment of multiple cell-surface and secreted molecules. MicroRNAs have tremendous potential for shaping neural circuitry by fine-tuning the spatio-temporal expression of key synaptic effector molecules. The highly conserved microRNA miR-8 is required during late stages of neuromuscular synapse development in Drosophila. However, its role in initial synapse formation was previously unknown. Detailed analysis of synaptogenesis in this system now reveals that miR-8 is required at the earliest stages of muscle target contact by RP3 motor axons. We find that the localization of multiple synaptic cell adhesion molecules (CAMs) is dependent on the expression of miR-8, suggesting that miR-8 regulates the initial assembly of synaptic sites. Using stable isotope labelling in vivo and comparative mass spectrometry, we find that miR-8 is required for normal expression of multiple proteins, including the CAMs Fasciclin III (FasIII) and Neuroglian (Nrg). Genetic analysis suggests that Nrg and FasIII collaborate downstream of miR-8 to promote accurate target recognition. Unlike the function of miR-8 at mature larval neuromuscular junctions, at the embryonic stage we find that miR-8 controls key effectors on both sides of the synapse. MiR-8 controls multiple stages of synapse formation through the coordinate regulation of both pre- and postsynaptic cell adhesion proteins. PMID- 25135981 TI - Towards evidence based medicine for paediatricians. PMID- 25135979 TI - Postnatal signalling with homeoprotein transcription factors. AB - Homeoprotein (HP) transcription factors were originally identified for their embryonic cell-autonomous developmental functions. In this review, we discuss their postnatal and adult physiological functions based on the study of Otx2, Engrailed-1 and Engrailed-2 (collectively Engrailed). For Engrailed, we discuss its function in the cell-autonomous regulation of ventral midbrain dopaminergic neuron survival and physiology and in the non-cell-autonomous maintenance of axons. For Otx2, we describe how the protein is expressed in the choroid plexus and transported into cortical parvalbumin cells where it regulates plasticity in the visual cortex. These two examples illustrate how the understanding of HP postnatal and adult functions, including signalling functions, may lead to the identification of disease-associated genetic pathways and to the development of original therapeutic strategies. PMID- 25135980 TI - The role of epigenetic-related codes in neurocomputation: dynamic hardware in the brain. AB - This paper presents a review of recent work on the role that two epigenetic related systems may play in information processing mechanisms in the brain. The first consists of exosomes that transport epigenetic-related molecules between neurons. The second consists of homeoproteins like Otx2 that carry information from sense organs to primary sensory cortex. There is developing evidence that presynaptic neurons may be able to modulate the fine microanatomical structure in the postsynaptic neuron. This may be conducted by three mechanisms, of which the first is well established and the latter two are novel. (i) By the well established activation of receptors that trigger a chain of signalling molecules (second messengers) that result in the upregulation and/or activation of a transcription factor. The two novel systems are the exosome system and homeoproteins. (ii) Exosomes are small vesicles that are released upon activation of the axon terminal, traverse the synaptic cleft, probably via astrocytes and are taken up by the postsynaptic neuron. They carry a load of signalling proteins and a variety of forms of RNA. These loads may then be transported widely throughout the postsynaptic neuron and engineer modulations in the fine structure of computational machinery by epigenetic-related processes. (iii) Otx2 is a transcription factor that, inter alia, controls the development and survival of PV+ GABAergic interneurons (PV cells) in the primary visual cortex. It is synthesized in the retina and is transported to the cortex by a presently unknown mechanism that probably includes direct cell-to-cell transfer, and may, or may not, include transfer by the dynein and exosome systems in addition. These three mechanisms explain a quantity of data from the field of de- and reafferentation plasticity. These data show that the modality of the presynaptic neuron controls to a large extent the modality of the postsynaptic neuron. However, the mechanism that effects this is currently unknown. The exosome and the homeoprotein hypotheses provide novel explanations to add to the well-established earlier mechanism described above. PMID- 25135983 TI - Outcome of coronary artery bypass grafting in a tertiary-care center in Pakistan. AB - BACKGROUND: Coronary artery bypass grafting and percutaneous coronary intervention are revascularization options for significant coronary artery disease. While international data support the use of coronary artery bypass in high-risk groups, regional data on outcomes in these groups are rare. We conducted a retrospective study to determine the outcomes of patients undergoing coronary artery bypass for left main and multivessel disease. METHODS: Two thousand eight hundred and fifty-one patients undergoing coronary artery bypass at the Aga Khan University Hospital from 2006 to 2013 were included; patients undergoing redo surgery were excluded. Demographic data, comorbidities, angiography findings, in-hospital complications, one-month and one-year follow-up were analyzed. RESULTS: Of the 2851 patients, 568 had left main disease (group 1) and 2283 (group 2) had multivessel disease (>=2 vessels excluding the left main). Group 1 had significantly more chronic lung disease, cardiogenic shock, and congestive heart failure than group 2 (p < 0.001); 50.6% of patients were diabetic and 71.8% were hypertensive. Mortality was 5.1% and 2.2% during hospital stay, 6.5% and 2.6% at 30 days, and 6.7% and 2.7% at 1 year in groups 1 and 2, respectively. CONCLUSION: Our comparable results and international data advocate revision of the current practice of using percutaneous coronary intervention over coronary artery bypass in the developing world. Institutional results are essential to determine the outcome of coronary artery bypass in high-risk populations with a high burden of diabetes and hypertension. We noted increased complications and mortality in patients with left main rather than multivessel disease. PMID- 25135985 TI - Enhancing the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer. AB - OBJECTIVE: The Japanese classification of peritoneal metastases from colorectal cancer is easy to use for general surgeons in routine clinical practice. However, the objectivity of this classification has not been determined. This study aimed to clarify the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer. METHODS: The data of patients with Stage IV colorectal cancer between 1991 and 2007 in 16 hospitals, who were members of the Japanese Society for Cancer of the Colon and Rectum, were investigated. The size, number and extent (nine areas) of peritoneal metastases according to the Japanese classification (P1, P2 and P3) were investigated using Akaike's information criterion. RESULTS: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 had hematogenous metastases. The minimum Akaike's information criterion was obtained with the cutoff value of one area for P1 metastasis and two or more areas for P2 metastasis (P < 0.0001). When P2 metastasis was compared with P3 metastasis, the cutoff value of the number of peritoneal metastases was 10. CONCLUSIONS: The present study proposes a revision that would give objectivity to the present Japanese classification as follows: P1 is defined as peritoneal metastases 20 mm or smaller confined to one area; P2 is defined as 10 or fewer peritoneal metastases disseminated in two or more areas, or peritoneal metastases confined to one area but the size is >20 mm and P3 is defined as >10 peritoneal metastases disseminated in two or more areas. PMID- 25135984 TI - Circulating tumor cells correlate with recurrence in stage III small-cell lung cancer after systemic chemoradiotherapy and prophylactic cranial irradiation. AB - OBJECTIVE: We investigated the correlation between circulating tumor cells and the incidence of brain metastases as a first site of recurrence among patients with small-cell lung cancer after systemic chemoradiotherapy and prophylactic cranial irradiation. In addition, we assessed the contribution of circulating tumor cells for planning the appropriate total dose of prophylactic cranial irradiation for small-cell lung cancer. METHODS: Patients (n = 112) with diagnosed Stage III small-cell lung cancer were treated with four cycles of platinum-based regimen and concurrent chest irradiation, and then prophylactic cranial irradiation. Blood samples for circulating tumor cell analysis were obtained before the initiation of chemotherapy and after the first and fourth cycle of chemotherapy. RESULTS: Circulating tumor cells after the first cycle of chemotherapy correlated with tumor response after completion of chemotherapy (P = 0.012). Patients with brain as the first site suffered a higher rate of further metastases to other organs, and local recurrence, compared with those whose first site was the other organs (P < 0.001), and their survival rates were worse. Circulating tumor cells at baseline were the sole independent prognostic factor for specific progression-free survival. Receiver operating characteristic curves based on median specific progression-free survival revealed a circulating tumor cell cutoff at baseline of 218, and circulating tumor cells <=218 at baseline correlated with significantly higher progression-free survival (P = 0.007), specific progression-free survival (P = 0.001) and overall survival (P = 0.001). CONCLUSIONS: Circulating tumor cells prior to the initiation of chemotherapy are a valuable predictor of specific progression-free survival in Stage III small cell lung cancer. For patients with circulating tumor cells >218, prophylactic cranial irradiation at a total dose of 30 Gy in 15 fractions is insufficient. PMID- 25135987 TI - Delayed bronchobiliary fistula and cholangiolithiasis following percutaneous radio frequency ablation for hepatocellular carcinoma. AB - Although percutaneous radio frequency ablation for hepatocellular carcinoma is a minimally invasive therapy, there are some complications reported; major complications include hemorrhage (0.477%), hepatic injuries (1.690%), and extrahepatic organ injuries (0.691%). We, for the first time, described a rare complication of delayed bronchobiliary fistula and cholangiolithiasis in common bile duct following radio frequency ablation and the salvage treatment in a patient with chronic hepatitis B virus infection. Surgeons should be aware of severe and rare complications before deciding the ablation area and when performing radio frequency ablation, and should be aware of the relevant salvage treatment. PMID- 25135986 TI - Endotoxin-induced lung alveolar cell injury causes brain cell damage. AB - Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with >=2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. PMID- 25135989 TI - Focal therapy will become a standard option for selected men with localized prostate cancer. PMID- 25135988 TI - Inclusion of endogenous hormone levels in risk prediction models of postmenopausal breast cancer. AB - PURPOSE: Endogenous hormones are risk factors for postmenopausal breast cancer, and their measurement may improve our ability to identify high-risk women. Therefore, we evaluated whether inclusion of plasma estradiol, estrone, estrone sulfate, testosterone, dehydroepiandrosterone sulfate, prolactin, and sex hormone binding globulin (SHBG) improved risk prediction for postmenopausal invasive breast cancer (n = 437 patient cases and n = 775 controls not using postmenopausal hormones) in the Nurses' Health Study. METHODS: We evaluated improvement in the area under the curve (AUC) for 5-year risk of invasive breast cancer by adding each hormone to the Gail and Rosner-Colditz risk scores. We used stepwise regression to identify the subset of hormones most associated with risk and assessed AUC improvement; we used 10-fold cross validation to assess model overfitting. RESULTS: Each hormone was associated with breast cancer risk (odds ratio doubling, 0.82 [SHBG] to 1.37 [estrone sulfate]). Individual hormones improved the AUC by 1.3 to 5.2 units relative to the Gail score and 0.3 to 2.9 for the Rosner-Colditz score. Estrone sulfate, testosterone, and prolactin were selected by stepwise regression and increased the AUC by 5.9 units (P = .003) for the Gail score and 3.4 (P = .04) for the Rosner-Colditz score. In cross validation, the average AUC change across the validation data sets was 6.0 (P = .002) and 3.0 units (P = .03), respectively. Similar results were observed for estrogen receptor-positive disease (selected hormones: estrone sulfate, testosterone, prolactin, and SHBG; change in AUC, 8.8 [P < .001] for Gail score and 5.8 [P = .004] for Rosner-Colditz score). CONCLUSION: Our results support that endogenous hormones improve risk prediction for invasive breast cancer and could help identify women who may benefit from chemoprevention or more screening. PMID- 25135990 TI - Calcium/magnesium infusion for oxaliplatin-induced neuropathy: protective or not? PMID- 25135991 TI - Patterns of relapse in patients with clinical stage I testicular cancer managed with active surveillance. AB - PURPOSE: To evaluate the performance of active surveillance as a management strategy in broad populations and to inform the development of surveillance schedules by individual patient data regarding timing and type of relapse. METHODS: Retrospective study including data from 2,483 clinical stage I (CSI) patients, 1,139 CSI nonseminoma and 1,344 CSI seminoma managed with active surveillance, with the majority treated between 1998 and 2010. Clinical outcomes including relapse and death, time distribution, extent of relapse and method of relapse detection observed on active surveillance were recorded. RESULTS: Relapse occurred in 221 (19%) CSI-nonseminoma and 173 (13%) CSI-seminoma patients. Median time to relapse was 4 months (range, 2-61 months), 8 months (range, 2-77 months) and 14 months (range, 2-84 months) for lymphovascular invasion-positive CSI nonseminoma, lymphovascular invasion-negative CSI nonseminoma and CSI seminoma. Most relapses were observed within the first 2 years/3 years after orchiectomy for CSI nonseminoma (90%)/CSI seminoma (92%). Relapses were detected by computed tomography scan/tumor-markers in 87%/3% of seminoma recurrences, in 48%/38% of lymphovascular invasion-negative and 41%/61% of lymphovascular invasion-positive patients, respectively. 90% of CSI-nonseminoma and 99% of CSI-seminoma relapses exhibited International Germ Cell Collaborative Group good-risk features. Three patients with CSI nonseminoma died of disease (0.3%). One patient with CSI seminoma and two patients with CSI nonseminoma died because of treatment-related events. Overall, advanced disease was seen in both early- and late-relapse patients. All late recurrences were cured with standard therapy. Five-year disease-specific survival was 99.7% (95% CI, 99.24% to 99.93%). CONCLUSION: Active surveillance for CSI testis cancer leads to excellent outcomes. The vast majority of relapses occur within 2 years of orchiectomy for CSI nonseminoma and within 3 years for CSI seminoma. Late and advanced stage relapse are rarely seen. These data may inform further refinement of rationally designed surveillance schedules. PMID- 25135993 TI - Reply to M. Valerio et al. PMID- 25135992 TI - Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study. AB - PURPOSE: Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. PATIENTS AND METHODS: Eligible patients were adults with newly diagnosed untreated stages II to IV CD20(+) DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. RESULTS: In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively). CONCLUSION: R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome. PMID- 25135995 TI - Reply to C.d. Atkins and a. Avan et Al. PMID- 25135994 TI - Radiation field design in the ACOSOG Z0011 (Alliance) Trial. AB - PURPOSE: ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial. METHODS: We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review. RESULTS: Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border <= 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using >= three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields. CONCLUSION: Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone. PMID- 25135996 TI - Estimating the value of intravenous calcium and magnesium in ameliorating oxaliplatin-induced neuropathy. PMID- 25135997 TI - Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab. AB - PURPOSE: To investigate the impact and mechanisms of vitamin D deficiency (VDD) on the outcome of elderly patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Three hundred fifty-nine pretreatment 25-hydroxyvitamin D3 (25[OH]D3) serum levels from the RICOVER-60 study (Six Versus Eight Cycles of Biweekly CHOP-14 With or Without Rituximab in Elderly Patients With Aggressive CD20+ B-Cell Lymphomas) and 63 from the RICOVER-noRTh study (an amendment to the RICOVER-60 study in which patients received six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone administered at an interval of 2 weeks plus two cycles of rituximab [R-CHOP-14], but without radiotherapy) were determined by chemoluminescent immunoassay. Rituximab-mediated cellular cytotoxicity (RMCC) was assessed by lactate dehydrogenase release assay of CD20+ Daudi cells. RESULTS: RICOVER-60 patients with VDD (<= 8 ng/mL) and vitamin D levels more than 8 ng/mL treated with rituximab had 3-year event-free survival (EFS) of 59% and 79% and 3-year overall survival (OS) of 70% and 82%, respectively. These differences were significant in a multivariable analysis adjusting for International Prognostic Index risk factors with a hazard ratio (HR) of 2.1 (P = .008) for EFS and 1.9 (P = .040) for OS. EFS was not significantly different in patients with vitamin D levels <= 8 or more than 8 ng/mL (HR, 1.2; P = .388) treated without rituximab. This was confirmed in an independent validation set of 63 RICOVER-noRTh patients. RMCC increased significantly (P < .001) in seven of seven individuals with VDD after substitution and normalization of their vitamin D levels. CONCLUSION: VDD is a risk factor for elderly patients with DLBCL treated with R-CHOP. That VDD impairs RMCC and substitution improves RMCC strongly suggests that vitamin D substitution enhances rituximab efficacy, which must be confirmed in appropriately designed prospective trials addressing VDD and substitution not only in DLBCL, but also in malignancies treated with other antibodies, of which the major mechanism of action is antibody-dependent cellular cytotoxicity (eg, trastuzumab in breast cancer and cetuximab in colorectal cancer). PMID- 25135998 TI - Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study. AB - PURPOSE: Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30(+) PTCL. PATIENTS AND METHODS: Patients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prespecified comparisons of the two treatment approaches. RESULTS: After sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n = 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (>= 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%). CONCLUSION: Brentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30(+) PTCL. A randomized phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No. NCT01777152). PMID- 25135999 TI - Strength and function response to clinical interventions of older women categorized by weakness and low lean mass using classifications from the Foundation for the National Institute of Health sarcopenia project. AB - BACKGROUND: The Foundation for the National Institutes of Health Sarcopenia Project developed data-driven cut-points for clinically meaningful weakness and low lean body mass. This analysis describes strength and function response to interventions based on these classifications. METHODS: In data from four intervention studies, 378 postmenopausal women with baseline and 6-month data were evaluated for change in grip strength, appendicular lean mass corrected for body mass index, leg strength and power, and short physical performance battery (SPPB). Clinical interventions included hormones, exercise, and nutritional supplementation. Differences in outcomes were evaluated between (i) those with and without weakness and (ii) those with weakness and low lean mass or with one but not the other. We stratified analyses by slowness (walking speed <= 0.8 m/s) and by treatment assignment. RESULTS: The women (72+/-7 years; body mass index of 26+/-5kg/m(2)) were weak (33%), had low lean mass (14%), or both (6%). Those with weakness increased grip strength, lost less leg power, and gained SPPB score (p < .05) compared with nonweak participants. Stratified analyses were similar for grip strength and SPPB. With lean mass in the analysis, individuals with weakness had larger gains in grip strength and SPPB scores regardless of low lean mass (p < .01). CONCLUSIONS: Older women with clinically meaningful muscle weakness increased grip strength and SPPB, regardless of the presence of low lean mass following treatment with interventions for frailty. Thus, results suggest that muscle weakness, as defined by the Foundation for the National Institutes of Health Sarcopenia Project, appears to be a treatable symptom. PMID- 25136001 TI - Becoming centenarians: disease and functioning trajectories of older US Adults as they survive to 100. AB - BACKGROUND: Little is known about the health and functioning of individuals who become centenarians in the years prior to reaching age 100. We examined long-term trajectories of disease, disability, and cognitive function in a sample of U.S. centenarians to determine how their aging experience differs from their nonsurviving cohort counterparts, and if there is heterogeneity in the aging experience of centenarians. METHODS: Data are from the 1993-2010 waves of the nationally representative Health and Retirement Study. Among those who had the potential to become centenarians, we identified 1,045 respondents who died before reaching age 100 and 96 who survived to their 100th birthday. Respondents, or their proxies, reported on diagnosis of six major diseases (hypertension, heart disease, lung disease, stroke, cancer, and diabetes), limitations in activities of daily living, and cognitive function. RESULTS: As they age to 100, centenarians are generally healthier than nonsurviving members of their cohort, and a number of individuals who become centenarians reach 100 with no self reported diseases or functional impairments. About 23% of centenarians reached age 100 with no major chronic disease and approximately the same number had no disability (18%). Over half (55%) reached 100 without cognitive impairment. Disease and functioning trajectories of centenarians differ by sex, education, and marital status. CONCLUSIONS: While some centenarians have poor health and functioning upon reaching age 100, others are able to achieve exceptional longevity in relatively good health and without loss of functioning. This study underscores the importance of examining variation in the growing centenarian population. PMID- 25136000 TI - Age-related decline of autocrine pituitary adenylate cyclase-activating polypeptide impairs angiogenic capacity of rat cerebromicrovascular endothelial cells. AB - Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging. PMID- 25136002 TI - Brain pathology contributes to simultaneous change in physical frailty and cognition in old age. AB - OBJECTIVE: First, we tested the hypothesis that the rate of change of physical frailty and cognitive function in older adults are correlated. Next, we examined if their rates of change are associated with the same brain pathologies. METHODS: About 2,167 older adults participating in the Religious Orders Study and the Rush Memory and Aging Project had annual clinical evaluations. Bivariate random coefficient models were used to estimate simultaneously the rates of change in both frailty and cognition, and the correlation of change was characterized by a joint distribution of the random effects. Then, we examined whether postmortem indices from deceased were associated with the rate of change of frailty and cognition. RESULTS: During an average follow-up of 6 years, frailty worsened by 0.09 unit/y and cognition declined by 0.08 unit/y. Most individuals showed worsening frailty and cognition (82.8%); 17% showed progressive frailty alone and <1% showed only cognitive decline. The rates of change of frailty and cognition were strongly correlated (rho = -0.73, p < .001). Among deceased (N = 828), Alzheimer's disease pathology, macroinfarcts, and nigral neuronal loss showed independent associations with the rate of change in both frailty and cognition (all ps < .001). In these models, demographics explained about 9% of the variation in individual rate of change in frailty, and neuropathologies explained about 8%. In contrast, demographics and neuropathologies accounted for 2% and 30%, respectively, of the variance in the cognitive decline. CONCLUSION: The rates of change in frailty and cognition are strongly correlated and this may be due in part because they share a common pathologic basis. PMID- 25136004 TI - Molecular characterization of Streptococcus agalactiae isolates harboring small erm(T)-carrying plasmids. AB - Among 1,827 group B Streptococcus (GBS) strains collected between 2006 and 2013 by the French National Reference Center for Streptococci, 490 (26.8%) strains were erythromycin resistant. The erm(T) resistance gene was found in six strains belonging to capsular polysaccharides Ia, III, and V and was carried by the same mobilizable plasmid, which could be efficiently transferred by mobilization to GBS and Enterococcus faecalis recipients, thus promoting a broad dissemination of erm(T). PMID- 25136005 TI - EUCAST testing of Isavuconazole susceptibility in Aspergillus: comparison of results for Inoculum standardization using Conidium counting versus optical density. AB - The EUCAST E.DEF9.1 standard recommends standardization of the inoculum concentration by conidium counting using a hemocytometer rather than a spectrophotometer. In this study, we investigated whether the choice of these methods influenced isavuconazole MICs. A blinded collection of 30 molecularly characterized azole-resistant isolates and 10 wild-type Aspergillus fumigatus isolates was shared with four different laboratories. Additionally, each laboratory selected approximately 100 A. fumigatus isolates and 50 isolates each of A. flavus, A. nidulans, A. niger, and A. terreus (1,237 isolates in total). Three laboratories (laboratories 1 to 3) used conidium counting. One laboratory standardized the inoculum using a spectrophotometer (that is, by use of the optical density [OD]) and is referred to as the OD laboratory. Correlation coefficients, intraclass correlation coefficients, and essential agreement were calculated, and 2-log-unit differences were assessed (paired t test). The MIC range for the blinded collection was 0.25 to 16 mg/liter, and a 1-dilution-step difference between the MIC50 and MIC90 across the four laboratories was detected and a 2-dilution-step difference between the modal MICs was detected. Compared to the results for laboratories 1 and 2, a significant correlation was found for the OD laboratory MIC data (correlation coefficients, 0.85 and 0.93, respectively; intraclass correlation coefficients, 0.88 and 0.96, respectively). The number of mutant isolates whose MICs overlapped those of the wild-type isolates was the lowest for the OD laboratory (14/30 [46.7%] mutant isolates), whereas the numbers were 18/30 (60%) isolates for laboratory 1, 17/30 (56.7%) isolates for laboratory 2, and 21/30 (70%) isolates for laboratory 3. For the A. flavus, A. fumigatus, A. nidulans, A. niger, and A. terreus isolates, comparative analysis again defined the MIC distributions from the OD laboratory to be in excellent agreement with those from laboratories 1 and 2 across all five Aspergillus spp. The findings suggest that EUCAST testing using OD determination is an appropriate alternative for standardization of Aspergillus inoculum concentrations. PMID- 25136006 TI - Comparison of in vivo and in vitro pharmacodynamics of a humanized regimen of 600 milligrams of Ceftaroline Fosamil every 12 hours against Staphylococcus aureus at initial inocula of 106 and 108 CFU per milliliter. AB - In light of the in vivo/in vitro discordance among beta-lactams against Gram negative pathogens, we compared the in vivo pharmacodynamics of humanized ceftaroline against 9 Staphylococcus aureus strains (MICs of 0.13 to 1 mg/liter) from published in vitro studies using standard and high inocula in the murine thigh infection model. Consistent with the in vitro findings, mean reductions of >=1 log10 CFU were observed for ceftaroline against all strains using both standard and high inocula. These results suggest in vivo/in vitro concordance with no observed inoculum effect. PMID- 25136003 TI - Effects of tenofovir on cytokines and nucleotidases in HIV-1 target cells and the mucosal tissue environment in the female reproductive tract. AB - Tenofovir (TFV) is a reverse transcriptase inhibitor used in microbicide preexposure prophylaxis trials to prevent HIV infection. Recognizing that changes in cytokine/chemokine secretion and nucleotidase biological activity can influence female reproductive tract (FRT) immune protection against HIV infection, we tested the hypothesis that TFV regulates immune protection in the FRT. Epithelial cells, fibroblasts, CD4(+) T cells, and CD14(+) cells were isolated from the endometrium (Em), endocervix (Cx), and ectocervix (Ecx) following hysterectomy. The levels of proinflammatory cytokines (macrophage inflammatory protein 3alpha [MIP-3alpha], interleukin 8 [IL-8], and tumor necrosis factor alpha [TNF-alpha]), the expression levels of specific nucleotidases, and nucleotidase biological activities were analyzed in the presence or absence of TFV. TFV influenced mRNA and/or protein cytokines and nucleotidases in a cell- and site-specific manner. TFV significantly enhanced IL 8 and TNF-alpha secretion by epithelial cells from the Em and Ecx but not from the Cx. In contrast, in response to TFV, IL-8 secretion was significantly decreased in Em and Cx fibroblasts but increased with fibroblasts from the Ecx. When incubated with CD4(+) T cells from the FRT, TFV increased IL-8 (Em and Ecx) and TNF-alpha (Cx and Ecx) secretion levels. Moreover, when incubated with Em CD14(+) cells, TFV significantly increased MIP-3alpha, IL-8, and TNF-alpha secretion levels relative to those of the controls. In contrast, nucleotidase biological activities were significantly decreased by TFV in epithelial (Cx) and CD4(+) T cells (Em) but increased in fibroblasts (Em). Our findings indicate that TFV modulates proinflammatory cytokines, nucleotidase gene expression, and nucleotidase biological activity in epithelial cells, fibroblasts, CD4(+) T cells, and CD14(+) cells at distinct sites within the FRT. PMID- 25136007 TI - Triclosan can select for an AdeIJK-overexpressing mutant of Acinetobacter baumannii ATCC 17978 that displays reduced susceptibility to multiple antibiotics. AB - In order to determine if triclosan can select for mutants of Acinetobacter baumannii ATCC 17978 that display reduced susceptibilities to antibiotics, we isolated a triclosan-resistant mutant, A. baumannii AB042, by serial passaging of A. baumannii ATCC 17978 in growth medium supplemented with triclosan. The antimicrobial susceptibility of AB042 was analyzed by the 2-fold serial dilution method. Expression of five different resistance-nodulation-division (RND) pump encoding genes (adeB, adeG, adeJ, A1S_2818, and A1S_3217), two outer membrane porin-encoding genes (carO and oprD), and the MATE family pump-encoding gene abeM was analyzed using quantitative reverse transcriptase (qRT) PCR. A. baumannii AB042 exhibited elevated resistance to multiple antibiotics, including piperacillin-tazobactam, doxycycline, moxifloxacin, ceftriaxone, cefepime, meropenem, doripenem, ertapenem, ciprofloxacin, aztreonam, tigecycline, and trimethoprim-sulfamethoxazole, in addition to triclosan. Genome sequencing of A. baumannii AB042 revealed a (116)G->V mutation in fabI, the gene encoding the target enzyme for triclosan. Expression analysis of efflux pumps showed overexpression of the AdeIJK pump, and sequencing of adeN, the gene that encodes the repressor of the adeIJK operon, revealed a 73-bp deletion which would cause a premature termination of translation, resulting in an inactive truncated AdeN protein. This work shows that triclosan can select for mutants of A. baumannii that display reduced susceptibilities to multiple antibiotics from chemically distinct classes in addition to triclosan resistance. This multidrug resistance can be explained by the overexpression of the AdeIJK efflux pump. PMID- 25136008 TI - Identification and characterization of linezolid-resistant cfr-positive Staphylococcus aureus USA300 isolates from a New York City medical center. AB - The cfr gene was identified in three linezolid-resistant USA300 methicillin resistant Staphylococcus aureus (MRSA) isolates collected over a 3-day period at a New York City medical center in 2011 as part of a routine surveillance program. Each isolate possessed a plasmid containing a pSCFS3-like cfr gene environment. Transformation of the cfr-bearing plasmids into the S. aureus ATCC 29213 background recapitulated the expected Cfr antibiogram, including resistance to linezolid, tiamulin, clindamycin, and florfenicol and susceptibility to tedizolid. PMID- 25136009 TI - In vivo efficacy of apramycin in murine infection models. AB - Apramycin is a unique aminoglycoside with a dissociation of antibacterial activity and ototoxicity. We assessed the antibacterial efficacy of apramycin in two murine models of infection, Mycobacterium tuberculosis aerosol infection and Staphylococcus aureus septicemia. In both infection models, the efficacy of apramycin was comparable to that of amikacin. These results suggest that apramycin has the potential to become a clinically useful agent against drug resistant pathogens and support further development of this promising unique aminoglycoside. PMID- 25136010 TI - Role of PBPD1 in stimulation of Listeria monocytogenes biofilm formation by subminimal inhibitory beta-lactam concentrations. AB - Disinfectant-tolerant Listeria monocytogenes biofilms can colonize surfaces that come into contact with food, leading to contamination and, potentially, food borne illnesses. To better understand the process of L. monocytogenes biofilm formation and dispersal, we screened 1,120 off-patent FDA-approved drugs and identified several that modulate Listeria biofilm development. Among the hits were more than 30 beta-lactam antibiotics, with effects ranging from inhibiting (<=50%) to stimulating (>=200%) biofilm formation compared to control. Most beta lactams also dispersed a substantial proportion of established biofilms. This phenotype did not necessarily involve killing, as >50% dispersal could be achieved with concentrations as low as 1/20 of the MIC of some cephalosporins. Penicillin-binding protein (PBP) profiling using a fluorescent penicillin analogue showed similar inhibition patterns for most beta-lactams, except that biofilm-stimulatory drugs did not bind PBPD1, a low-molecular-weight d,d carboxypeptidase. Compared to the wild type, a pbpD1 mutant had an attenuated biofilm response to stimulatory beta-lactams. The cephalosporin-responsive CesRK two-component regulatory system, whose regulon includes PBPs, was not required for the response. The requirement for PBPD1 activity for beta-lactam stimulation of L. monocytogenes biofilms shows that the specific set of PBPs that are inactivated by a particular drug dictates whether a protective biofilm response is provoked. PMID- 25136012 TI - Validation of a model to predict the risk of nephrotoxicity in patients receiving colistin. AB - Despite concerns about its nephrotoxicity, colistin often remains the only effective agent for treating multidrug-resistant Gram-negative infections. Published studies have reported a wide range of nephrotoxicity risk factors. To assess the clinical utility of various models, we compared their performances for predicting the risk of nephrotoxicity. We identified a model demonstrating reasonable overall risk assessment, with an observed/expected ratio of 1.29 (95% confidence interval [CI], 0.68 to 1.90) and a positive predictive value of 87.5% for identifying patients at high risk of developing nephrotoxicity. PMID- 25136011 TI - Antimicrobial resistance in Salmonella enterica Serovar Typhi isolates from Bangladesh, Indonesia, Taiwan, and Vietnam. AB - We characterized Salmonella enterica serovar Typhi isolates from Bangladesh, Indonesia, Taiwan, and Vietnam to investigate their genetic relatedness and antimicrobial resistance. The isolates from Bangladesh and Vietnam were genetically closely related but were distant from those from Indonesia and Taiwan. All but a few isolates from Indonesia and Taiwan were susceptible to all antimicrobials tested. The majority of isolates from Bangladesh and Vietnam were multidrug resistant (MDR) and belonged to the widespread haplotype H58 clone. IncHI1 plasmids were detected in all MDR S. Typhi isolates from Vietnam but in only 15% of MDR isolates from Bangladesh. Resistance genes in the majority of MDR S. Typhi isolates from Bangladesh should reside in the chromosome. Among the isolates from Bangladesh, 82% and 40% were resistant to various concentrations of nalidixic acid and ciprofloxacin, respectively. Several resistance mechanisms, including alterations in gyrase A, the presence of QnrS, and enhanced efflux pumps, were involved in the reduced susceptibility and resistance to fluoroquinolones. Intensive surveillance is necessary to monitor the spread of chromosome-mediated MDR and fluoroquinolone-resistant S. Typhi emerging in Bangladesh. PMID- 25136014 TI - Ceftaroline-Fosamil efficacy against methicillin-resistant Staphylococcus aureus in a rabbit prosthetic joint infection model. AB - Ceftaroline (CPT), the active metabolite of the prodrug ceftaroline-fosamil (CPT F), demonstrates in vitro bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and is effective in rabbit models of difficult-to treat MRSA endocarditis and acute osteomyelitis. However, its in vivo efficacy in a prosthetic joint infection (PJI) model is unknown. Using a MRSA-infected knee PJI model in rabbits, the efficacies of CPT-F or vancomycin (VAN) alone and combined with rifampin (RIF) were compared. After each partial knee replacement with a silicone implant that fit into the tibial intramedullary canal was performed, 5 * 10(7) MRSA CFU (MICs of 0.38, 0.006, and 1 mg/liter for CPT, RIF, and VAN, respectively) was injected into the knee. Infected animals were randomly assigned to receive no treatment (controls) or CPT-F (60 mg/kg of body weight intramuscularly [i.m.]), VAN (60 mg/kg i.m.), CPT-F plus RIF (10 mg/kg i.m.), or VAN plus RIF starting 7 days postinoculation and lasting for 7 days. Surviving bacteria in crushed tibias were counted 3 days after ending treatment. Although the in vivo mean log10 CFU/g of CPT-treated (3.0 +/- 0.9, n = 12) and VAN-treated (3.5 +/- 1.1, n = 12) crushed bones was significantly lower than those of controls (5.6 +/- 1.1, n = 14) (P < 0.001), neither treatment fully sterilized the bones (3/12 were sterile with each treatment). The mean log10 CFU/g values for the antibiotics in combination with RIF were 1.9 +/- 0.5 (12/14 were sterile) for CPT-F and 1.9 +/- 0.5 (12/14 were sterile) for VAN. In this MRSA PJI model, the efficacies of CPT-F and VAN did not differ; thus, CPT appears to be a promising antimicrobial agent for the treatment of MRSA PJIs. PMID- 25136013 TI - Molecular features of community-associated extended-spectrum-beta-lactamase producing Escherichia coli strains in the United States. AB - We characterized 30 community-associated extended-spectrum-beta-lactamase producing Escherichia coli isolates collected from five hospitals in the United States. Nineteen sequence types were identified. All sequence type 131 (ST131) isolates had the fimH30 allele. IncFII-FIA-FIB was the most common replicon type among the blaCTX-M-carrying plasmids, followed by IncFII-FIA and IncA/C. Restriction analysis of the IncFII-FIA-FIB and IncFII-FIA plasmids yielded related profiles for plasmids originating from different hospitals. The plasmids containing blaCTX-M or blaSHV were stably maintained after serial passages. PMID- 25136015 TI - Safety, tolerability, and efficacy of GSK1322322 in the treatment of acute bacterial skin and skin structure infections. AB - GSK1322322 represents a new class of antibiotics that targets an essential bacterial enzyme required for protein maturation, peptide deformylase. This multicenter, randomized, phase IIa study compared the safety, tolerability, and efficacy of GSK1322322 at 1,500 mg twice daily (b.i.d.) with that of linezolid at 600 mg b.i.d. in patients suspected of having Gram-positive acute bacterial skin and skin structure infections (ABSSSIs). The primary endpoint was assessment of the safety of GSK1322322, and a key secondary endpoint was the number of subjects with a >=20% decrease in lesion area from the baseline at 48 and 72 h after treatment initiation. GSK1322322 administration was associated with mild-to moderate drug-related adverse events, most commonly, nausea, vomiting, diarrhea, and headache. Adverse events (86% versus 74%) and withdrawals (28% versus 11%) were more frequent in the GSK1322322-treated group. Treatment with GSK1322322 and linezolid was associated with >=20% decreases from the baseline in the lesion area in 73% (36/49) and 92% (24/26) of the patients, respectively, at the 48-h assessment and in 96% (44/46) and 100% (25/25) of the patients, respectively, at the 72-h assessment. Reductions in exudate/pus, pain, and skin infection scores were comparable between the GSK1322322 and linezolid treatments. The clinical success rates within the intent-to-treat population and the per-protocol population that completed this study were 67 and 91%, respectively, in the GSK1322322-treated group and 89 and 100%, respectively, in the linezolid-treated group. These results will be used to guide dose selection in future studies with GSK1322322 to optimize its tolerability and efficacy in patients with ABSSSIs. (This study has been registered at ClinicalTrials.gov under registration no. NCT01209078 and at http://www.gsk-clinicalstudyregister.com [PDF113414].). PMID- 25136016 TI - Efficacy of a Ceftazidime-Avibactam combination in a murine model of Septicemia caused by Enterobacteriaceae species producing ampc or extended-spectrum beta lactamases. AB - Avibactam is a novel non-beta-lactam beta-lactamase inhibitor that has been shown in vitro to inhibit class A, class C, and some class D beta-lactamases. It is currently in phase 3 of clinical development in combination with ceftazidime. In this study, the efficacy of ceftazidime-avibactam was evaluated in a murine septicemia model against five ceftazidime-susceptible (MICs of 0.06 to 0.25 MUg/ml) and 15 ceftazidime-resistant (MICs of 64 to >128 MUg/ml) species of Enterobacteriaceae, bearing either TEM, SHV, CTX-M extended-spectrum, or AmpC beta-lactamases. In the first part of the study, ceftazidime-avibactam was administered at ratios of 4:1 and 8:1 (wt/wt) to evaluate the optimal ratio for efficacy. Against ceftazidime-susceptible isolates of Klebsiella pneumoniae and Escherichia coli, ceftazidime and ceftazidime-avibactam demonstrated similar efficacies (50% effective doses [ED50] of <1.5 to 9 mg/kg of body weight), whereas against ceftazidime-resistant beta-lactamase-producing strains (ceftazidime ED50 of >90 mg/kg), the addition of avibactam restored efficacy to ceftazidime (ED50 dropped to <5 to 65 mg/kg). In a subsequent study, eight isolates (two AmpC and six CTX-M producers) were studied in the septicemia model. Ceftazidime-avibactam was administered at a 4:1 (wt/wt) ratio, and the efficacy was compared to that of the 4:1 (wt/wt) ratio of either piperacillin-tazobactam or cefotaxime-avibactam. Against the eight isolates, ceftazidime-avibactam was the more effective combination, with ED50 values ranging from 2 to 27 mg/kg compared to >90 mg/kg and 14 to >90 mg/kg for piperacillin-tazobactam and cefotaxime-avibactam, respectively. This study demonstrates that the potent in vitro activity observed with the ceftazidime-avibactam combination against ceftazidime-resistant Enterobacteriaceae species bearing class A and class C beta lactamases translated into good efficacy in the mouse septicemia model. PMID- 25136017 TI - A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel Imidazolopiperazine KAF156 to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers. AB - KAF156 belongs to a new class of antimalarial, the imidazolopiperazines, and is currently in clinical development for the treatment of uncomplicated malaria. This first-in-human, single- and multiple-ascending-dose study in 70 healthy male volunteers determined the maximum oral dose of KAF156 tolerated by healthy adults and derived pharmacokinetic data (including preliminary food effect) to enable dose calculations for malaria patients. KAF156 was studied in single-dose cohorts (10 to 1,200 mg, including one 400-mg food effect cohort (4 to 10 subjects/cohort), and in multiple-dose cohorts (60 to 600 mg once daily for 3 days; 8 subjects/cohort). The follow-up period was 6 to 14 days after the last dose. KAF156 was tolerated, with self-limited mild to moderate gastrointestinal and neurological adverse events. In treated subjects after single doses, headache (n = 4; 11.1%), diarrhea (n = 3; 8.3%), dizziness (n = 3; 8.3%), and abdominal pain (n = 2; 5.6%) were the most common adverse events. Headache (n = 4; 16.7%), nausea (n = 3; 12.5%), upper respiratory tract infection (n = 3; 12.5%), and dizziness (n = 2; 8.3%) were the most common adverse events following multiple doses. KAF156 time to maximum concentration (Tmax) was between 1.0 and 6.0 h. Both the area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased more than dose-proportionally in both single- and multiple ascending-dose cohorts (terminal half-life, 42.5 to 70.7 h). There was no significant accumulation over 3-day repeated administration. The extent of absorption was not significantly affected by food at a single dose of 400 mg, while mean Cmax decreased from 778 ng/ml to 627 ng/ml and Tmax was delayed from a median of 3.0 h under fasting conditions to 6.0 h under fed conditions. Renal elimination is a minor route. PMID- 25136018 TI - Changes in pneumococcal serotypes and antimicrobial resistance after introduction of the 13-valent conjugate vaccine in the United States. AB - Ongoing surveillance for Streptococcus pneumoniae is needed to assess the impact of the pneumococcal conjugate vaccine introduced in 2010 (PCV13). Forty-two U.S. centers submitted S. pneumoniae isolates between 1 October 2012 and 31 March 2013. Susceptibility testing was performed by use of a broth dilution method as recommended by the Clinical and Laboratory Standards Institute. Serotyping was performed by multiplex PCR and the Quellung reaction. Multidrug resistance (MDR) was defined as nonsusceptibility to penicillin (PNSP; MIC >= 0.12 MUg/ml) combined with resistance to >=2 non-beta-lactam antimicrobials. Penicillin resistant S. pneumoniae (PRSP) was defined as a penicillin MIC of >=2 MUg/ml. For the 1,498 isolates collected during 2012-13, the PRSP and MDR rates were 14.2 and 21.0%, respectively. These percentages were lower than rates obtained in a surveillance study conducted 4 years earlier in 2008-09 (17.0 and 26.6%, respectively). The most common serotypes identified in 2012-13 were 3, 35B, and 19A, each representing 9 to 10% of all isolates. The largest percentage of PNSP in 2012-13 were found in serotypes 35B (24.8%), 19A (23.5%), and 15A (10.3%). Predominant PRSP serotypes were 19A (54.5%), 35B (28.2%), and 19F (7.0%). Major MDR serotypes were 19A (38.5%), 15A (16.9%), 6C (8.3%), and 35B (6.4%). The change in prevalence of PCV13 serotypes (43.4 to 27.1%) was primarily due to a decrease in serotype 19A strains, i.e., 22% of all strains in 2008-09 to 10% of all strains in 2012-13. Among the PNSP subset, serotypes showing a proportional increase were 35B, 15B, and 23B. Among MDR strains, the largest proportional increases were observed in serotypes 35B, 15B, and 23A. PMID- 25136019 TI - Use of microdosing and accelerator mass spectrometry to evaluate the pharmacokinetic linearity of a novel tricyclic GyrB/ParE inhibitor in rats. AB - Determining the pharmacokinetics (PKs) of drug candidates is essential for understanding their biological fate. The ability to obtain human PK information early in the drug development process can help determine if future development is warranted. Microdosing was developed to assess human PKs, at ultra-low doses, early in the drug development process. Microdosing has also been used in animals to confirm PK linearity across subpharmacological and pharmacological dose ranges. The current study assessed the PKs of a novel antimicrobial preclinical drug candidate (GP-4) in rats as a step toward human microdosing studies. Dose proportionality was determined at 3 proposed therapeutic doses (3, 10, and 30 mg/kg of body weight), and PK linearity between a microdose and a pharmacological dose was assessed in Sprague-Dawley rats. Plasma PKs over the 3 pharmacological doses were proportional. Over the 10-fold dose range, the maximum concentration in plasma and area under the curve (AUC) increased 9.5- and 15.8-fold, respectively. PKs from rats dosed with a (14)C-labeled microdose versus a (14)C labeled pharmacological dose displayed dose linearity. In the animals receiving a microdose and the therapeutically dosed animals, the AUCs from time zero to infinity were 2.6 ng . h/ml and 1,336 ng . h/ml, respectively, and the terminal half-lives were 5.6 h and 1.4 h, respectively. When the AUC values were normalized to a dose of 1.0 mg/kg, the AUC values were 277.5 ng . h/ml for the microdose and 418.2 ng . h/ml for the pharmacological dose. This 1.5-fold difference in AUC following a 300-fold difference in dose is considered linear across the dose range. On the basis of the results, the PKs from the microdosed animals were considered to be predictive of the PKs from the therapeutically dosed animals. PMID- 25136020 TI - Characterization of a novel AmpC beta-lactamase produced by a carbapenem resistant Cedecea davisae clinical isolate. AB - A Cedecea davisae isolate, which was intermediate or resistant to third generation cephalosporins and carbapenems, was recovered from a urine sample. Susceptibility testing, isoelectric focusing, and analysis of outer membrane proteins showed that AmpC beta-lactamase expression combined with porin deficiency accounted for the carbapenem resistance. A cloning experiment followed by phenotypic and enzymatic characterization identified a novel class C enzyme that was phylogenetically and biochemically close to the chromosome-borne beta lactamases of the genera Enterobacter and Citrobacter. PMID- 25136021 TI - In vitro combination of isavuconazole with micafungin or amphotericin B deoxycholate against medically important molds. AB - Whether isavuconazole, an extended-spectrum triazole, possesses synergistic activity in combination therapy with echinocandins or amphotericin B for the treatment of invasive molds infections has not been studied. Our in vitro combination studies showed that isavuconazole and micafungin are synergistically active against Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, and Cunninghamella bertholletiae. These results suggest that isavuconazole, in combination with micafungin, may have a role in the treatment of invasive aspergillosis and warrants further investigation. PMID- 25136022 TI - Novel insights into the mechanism of inhibition of MmpL3, a target of multiple pharmacophores in Mycobacterium tuberculosis. AB - MmpL3, a resistance-nodulation-division (RND) superfamily transporter, has been implicated in the formation of the outer membrane of Mycobacterium tuberculosis; specifically, MmpL3 is required for the export of mycolic acids in the form of trehalose monomycolates (TMM) to the periplasmic space or outer membrane of M. tuberculosis. Recently, seven series of inhibitors identified by whole-cell screening against M. tuberculosis, including the antituberculosis drug candidate SQ109, were shown to abolish MmpL3-mediated TMM export. However, this mode of action was brought into question by the broad-spectrum activities of some of these inhibitors against a variety of bacterial and fungal pathogens that do not synthesize mycolic acids. This observation, coupled with the ability of three of these classes of inhibitors to kill nonreplicating M. tuberculosis bacilli, led us to investigate alternative mechanisms of action. Our results indicate that the inhibitory effects of adamantyl ureas, indolecarboxamides, tetrahydropyrazolopyrimidines, and the 1,5-diarylpyrrole BM212 on the transport activity of MmpL3 in actively replicating M. tuberculosis bacilli are, like that of SQ109, most likely due to their ability to dissipate the transmembrane electrochemical proton gradient. In addition to providing novel insights into the modes of action of compounds reported to inhibit MmpL3, our results provide the first explanation for the large number of pharmacophores that apparently target this essential inner membrane transporter. PMID- 25136023 TI - Genetic and kinetic characterization of the novel AmpC beta-lactamases DHA-6 and DHA-7. AB - During a Spanish surveillance study, two natural variants of DHA beta-lactamases, DHA-6 and DHA-7, were found, with the replacements Ala226Thr and Phe322Ser, respectively, with respect to DHA-1. The DHA-6 and DHA-7 enzymes were isolated from Escherichia coli and Enterobacter cloacae clinical isolates, respectively. The aim of this study was to genetically, microbiologically, and biochemically characterize the DHA-6 and DHA-7 beta-lactamases. The blaDHA-6 and blaDHA-7 genes were located in the I1 and HI2 incompatibility group plasmids of 87.3 and 310.4 kb, respectively. The genetic contexts of blaDHA-6 and blaDHA-7 were similar to that already described for the blaDHA-1 gene and included the qnrB4 and aadA genes. The MICs for cephalothin, aztreonam, cefotaxime, and ceftazidime were 8- to 32-fold lower for DHA-6 than for DHA-1 or DHA-7 expressed in the same isogenic E. coli TG1 strain. Interestingly, the MIC for cefoxitin was higher in the DHA-6 expressing transformant than in DHA-1 or DHA-7. Biochemical studies with pure beta-lactamases revealed slightly lower catalytic efficiencies of DHA-6 against cephalothin, ceftazidime, and cefotaxime than those of DHA-1 and DHA-7. To understand this behavior, stability experiments were carried out and showed that the DHA-6 protein displayed significantly higher stability than the DHA-1 and DHA 7 enzymes. The proximity of Thr226 to the N terminus in the tertiary protein structure in DHA-6 may promote this stabilization and, consequently, may induce a slight reduction in the dynamic of this enzyme that primarily affects the hydrolysis of some of the bulkiest antibiotics. PMID- 25136024 TI - Pharmacokinetics of tedizolid in subjects with renal or hepatic impairment. AB - Two open-label, single-dose, parallel-group studies were conducted to characterize the pharmacokinetics of the novel antibacterial tedizolid and the safety of tedizolid phosphate, its prodrug, in renally or hepatically impaired subjects. Tedizolid pharmacokinetics in subjects with severe renal impairment without dialysis support was compared with that of matched control subjects with normal renal function. Effects of hemodialysis on tedizolid pharmacokinetics were determined in a separate cohort of subjects undergoing long-term hemodialysis. Effects of hepatic impairment on tedizolid pharmacokinetics were determined in subjects with moderate or severe hepatic impairment and compared with those of matched control subjects with normal hepatic function. Each participant received a single oral (hepatic impairment) or intravenous (renal impairment) dose of tedizolid phosphate at 200 mg; hemodialysis subjects received two doses (separated by 7 days), before and after dialysis, in a crossover fashion. The pharmacokinetics of tedizolid was similar in subjects with severe renal impairment and controls (~8% lower area under the concentration-time curve [AUC], with a nearly identical peak concentration) and in subjects undergoing hemodialysis before and after tedizolid phosphate administration (~9% lower AUC, with a 15% higher peak concentration); <10% of the dose was removed during 4 h of hemodialysis. Tedizolid pharmacokinetics was only minimally altered in subjects with moderate or severe hepatic impairment; the AUC was increased approximately 22% and 34%, respectively, compared with that of subjects in the control group. Tedizolid phosphate was generally well tolerated in all participants. These results suggest that tedizolid phosphate dose adjustments are not necessary in patients with any degree of renal or hepatic impairment. (This study has been registered at ClinicalTrials.gov under registration numbers NCT01452828 [renal study] and NCT01431833 [hepatic study].). PMID- 25136025 TI - Characterization of a P1-like bacteriophage carrying an SHV-2 extended-spectrum beta-lactamase from an Escherichia coli strain. AB - P1 bacteriophages lysogenize bacteria as independent plasmid-like elements. We describe here a P1-like bacteriophage, RCS47, carrying a blaSHV-2 gene, isolated from a clinical strain of Escherichia coli from phylogroup B1, and we report the prevalence of P1-like prophages in natural E. coli isolates. We found that 70% of the sequence of RCS47, a 115-kb circular molecule, was common to the reference P1 bacteriophage under GenBank accession no. AF234172.1, with the shared sequences being 99% identical. RCS47 had acquired two main foreign DNA fragments: a 9,636 bp fragment mobilized by two IS26 elements containing a blaSHV-2 gene, and an 8,544-bp fragment mobilized by two IS5 elements containing an operon encoding a dimethyl sulfoxide reductase. The reference P1 prophage plasmid replication gene belonged to the IncY incompatibility group, whereas that of RCS47 was from an unknown group. The lytic capacity of RCS47 and blaSHV-2 gene transduction, through the lysogenization of RCS47 in the recipient E. coli strains, were not demonstrated. The prevalence of P1-like prophages in various animal and human E. coli strain collections, as determined by the PCR detection of repL, the lytic replication gene, was 12.6%. No differences in the prevalences of these prophages were found between extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL producing strains (P = 0.69), but this prevalence was lower in phylogroup B2 than in the other phylogroups (P = 0.008), suggesting epistatic interactions between P1 family phages and the genetic background of E. coli strains. P1-like phages are part of the mobile elements that carry antibiotic resistance. The high prevalence of P1-like prophages suggests their role may be underestimated. PMID- 25136026 TI - Synthesis of metallo-beta-lactamase VIM-2 is associated with a fitness reduction in Salmonella enterica Serovar Typhimurium. AB - Antibiotic resistance, especially due to beta-lactamases, has become one of the main obstacles in the correct treatment of Salmonella infections; furthermore, antibiotic resistance determines a gain of function that may encompass a biological cost, or fitness reduction, to the resistant bacteria. The aim of this work was to determine in vitro if the production of the class B beta-lactamase VIM-2 determined a fitness cost for Salmonella enterica serovar Typhimurium. To that end the gene blaVIM-2 was cloned into the virulent strain S. Typhimurium SL1344, using both the tightly regulated pBAD22 vector and the natural plasmid pST12, for inducible and constitutive expression, respectively. Fitness studies were performed by means of motility, growth rate, invasiveness in epithelial cells, and plasmid stability. The expression of blaVIM-2 was accompanied by alterations in micro- and macroscopic morphology and reduced growth rate and motility, as well as diminished invasiveness in epithelial cells. These results suggest that VIM-2 production entails a substantial fitness cost for S. Typhimurium, which in turn may account for the extremely low number of reports of metallo-beta-lactamase-producing Salmonella spp. PMID- 25136027 TI - Association between vancomycin trough concentration and area under the concentration-time curve in neonates. AB - National treatment guidelines for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections recommend targeting a vancomycin 24-h area under the concentration-time curve (AUC0-24)-to-MIC ratio of >400. The range of vancomycin trough concentrations that best predicts an AUC0-24 of >400 in neonates is not known. This understanding would help clarify target trough concentrations in neonates when treating MRSA. A retrospective chart review from a level III neonatal intensive care unit was performed to identify neonates treated with vancomycin over a 5-year period. Vancomycin concentrations and clinical covariates were utilized to develop a one-compartment population pharmacokinetic model and examine the relationships between trough and AUC0-24 in the study neonates. Monte Carlo simulations were performed to examine the effect of dose, postmenstrual age (PMA), and serum creatinine level on trough and AUC0-24 achievement. A total of 1,702 vancomycin concentrations from 249 neonates were available for analysis. The median (interquartile range) PMA was 39 weeks (32 to 42 weeks) and weight was 2.9 kg (1.6 to 3.7 kg). Vancomycin clearance was predicted by weight, PMA, and serum creatinine level. At a trough of 10 mg/liter, 89% of the study neonates had an AUC0-24 of >400. Monte Carlo simulations demonstrated that troughs ranging from 7 to 11 mg/liter were highly predictive of an AUC0-24 of >400 across a range of PMA, serum creatinine levels, and vancomycin doses. However, a trough of >=10 mg/liter was not readily achieved in most simulated subgroups using routine starting doses. Higher starting doses frequently resulted in troughs of >20 mg/liter. A vancomycin trough of ~10 mg/liter is likely adequate for most neonates with invasive MRSA infections based on considerations of the AUC0-24. Due to pharmacokinetic and clinical heterogeneity in neonates, consistently achieving this target vancomycin exposure with routine starting doses is difficult. More robust clinical dosing support tools are needed to help clinicians with dose individualization. PMID- 25136028 TI - Tedizolid population pharmacokinetics, exposure response, and target attainment. AB - Tedizolid phosphate is a novel antibacterial prodrug that is rapidly and extensively converted to its active moiety, tedizolid. We developed a population pharmacokinetics (PK) model for tedizolid using pooled data from seven densely and sparsely sampled clinical trials evaluating oral and intravenous tedizolid. Model-derived exposure estimates were evaluated for relationships to select efficacy and safety outcomes. A two-compartment model with sigmoidal absorption, absolute bioavailability, and linear elimination described the PK data well. Variability was small (clearance, 31% coefficient of variation; volume, 13.4% coefficient of variation), and absolute bioavailability was high (86%). No clinically significant covariate effects on tedizolid PK were found. Based on phase 3 data evaluating 200-mg once-daily tedizolid for acute bacterial skin and skin structure infections (ABSSSI), no relationships were seen between various efficacy outcomes and estimated tedizolid exposure; the estimated exposure range (free-drug area under the concentration-time curve over 24 h at steady state [AUCss(0-24)], 7 to 50 MUg . h/ml) in these patients was modest. Safety data modeling, using once-daily doses of up to 400 mg, showed a small increase in the probability of an adverse event with increasing model-estimated tedizolid exposure; no such relationship was observed when specifically evaluating the 200 mg dose. There were no trends in neutrophil or platelet counts with increasing tedizolid exposure. Target attainment simulations for 200-mg tedizolid indicated a 98.31% probability of attaining the target measure (AUC for the free, unbound fraction of a drug [fAUC]/MIC = 3) against a Staphylococcus aureus strain for which the MIC was <=0.5 MUg/ml. These findings support 200-mg tedizolid once daily as the optimum dose for treatment of ABSSSI. PMID- 25136029 TI - Distinct roles of major peptidoglycan recycling enzymes in beta-Lactamase production in Shewanella oneidensis. AB - beta-Lactam antibiotics were the earliest discovered and are the most widely used group of antibiotics that work by inactivating penicillin-binding proteins to inhibit peptidoglycan biosynthesis. As one of the most efficient defense strategies, many bacteria produce beta-lactam-degrading enzymes, beta-lactamases, whose biochemical functions and regulation have been extensively studied. A signal transduction pathway for beta-lactamase induction by beta-lactam antibiotics, consisting of the major peptidoglycan recycling enzymes and the LysR type transcriptional regulator, AmpR, has been recently unveiled in some bacteria. Because inactivation of some of these proteins, especially the permease AmpG and the beta-hexosaminidase NagZ, results in substantially elevated susceptibility to the antibiotics, these have been recognized as potential therapeutic targets. Here, we show a contrasting scenario in Shewanella oneidensis, in which the homologue of AmpR is absent. Loss of AmpG or NagZ enhances beta-lactam resistance drastically, whereas other identified major peptidoglycan recycling enzymes are dispensable. Moreover, our data indicate that there exists a parallel signal transduction pathway for beta-lactamase induction, which is independent of either AmpG or NagZ. PMID- 25136030 TI - Correlation between subchondral bone plate thickness and cartilage degeneration in osteoarthritis of the ankle. AB - BACKGROUND: Osteoarthritis (OA) is characterized not only by cartilage degeneration, but also subchondral bone changes. The subchondral bone plate (SBP) plays an important role in cartilage metabolism, and elucidation of the relationship between the SBP and cartilage degeneration would be helpful to determine the most appropriate treatment strategy for ankle OA. The purpose of this study was to evaluate the SBP and to compare it with cartilage degeneration with arthroscopic findings. METHODS: Computed tomography (CT) was used to compare the thickness of the SBP of 11 ankle OA patients with that of 11 non-ankle OA patients in 9 areas of the talar dome. The French Society of Arthroscopy (SFA) grading system was used to analyze the relationship between findings on the thickness of SBP and on articular cartilage degeneration in ankle OA. RESULTS: The SBP in ankle OA was significantly thicker than that of the non-OA ankle. The more severe the articular cartilage degeneration, the thicker the SBP became. The SBP on the sclerotic trabecular bone was significantly thicker than that on decreased trabecular bone. The SFA grade for sclerotic subchondral bone was significantly higher than that for decreased trabecular bone. CONCLUSION: This study shows that the thickness of SBP and the findings of subchondral bone such as decreased trabecular bone and sclerosis in CT are related to the cartilage degeneration of ankle OA, although a small number of patients were analyzed. LEVEL OF EVIDENCE: Level III, comparative series. PMID- 25136031 TI - Prognostic value of computed tomography classification systems for intra articular calcaneus fractures. AB - BACKGROUND: There are several published computed tomography (CT) classification systems for calcaneus fractures, each validated by a different standard. The goal of this study was to measure which system would best predict clinical outcomes as measured by a widely used and validated musculoskeletal health status questionnaire. METHODS: Forty-nine patients with isolated intra-articular joint depression calcaneus fractures more than 2 years after treatment were identified. All had preoperative CT studies and were treated with open reduction and plate fixation using a lateral extensile approach. Four different blinded reviewers classified injuries according to the CT classification systems of Crosby and Fitzgibbons, Eastwood, and Sanders. Functional outcomes evaluated with a Musculoskeletal Functional Assessment (MFA). The mean follow-up was 4.3 years. RESULTS: The mean MFA score was 15.7 (SD = 11.6), which is not significantly different from published values for midfoot injuries, hindfoot injuries, or both, 1 year after injury (mean = 22.1, SD = 18.4). The classification systems of Crosby and Fitzgibbons, Eastwood, and Sanders, the number of fragments of the posterior facet, and payer status were not significantly associated with outcome as determined by the MFA. The Sanders classification trended toward significance. Anterior process comminution and surgeon's overall impression of severity were significantly associated with functional outcome. CONCLUSIONS: The amount of anterior process comminution was an important determinant of functional outcome with increasing anterior process comminution significantly associated with worsened functional outcome (P = .04). In addition, the surgeon's overall impression of severity of injury was predictive of functional outcome (P = .02), as determined by MFA. LEVEL OF EVIDENCE: Level III, comparative series. PMID- 25136032 TI - Re: Role of oncogenic K-Ras in cancer stem cell activation by aberrant Wnt/beta catenin signaling. PMID- 25136033 TI - Response. PMID- 25136034 TI - Manipulating microRNAs to regulate macrophage polarization in gliomas. PMID- 25136035 TI - Preclinical safety evaluation of human mesenchymal stem cell transplantation in cerebrum of nonhuman primates. AB - The efficacy of stem cell transplantation for promoting recovery of patients with neurological diseases, such as stroke, has been reported in several studies. However, the safety of the intracerebral transplantation of human mesenchymal stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide evidence for clinical application. A total of 24 M fascicularis were assigned to 3 groups randomly: low dose (3.0 * 10(5) cells/kg), high dose (2.5 * 10(6) cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or NS were injected into each monkey for 2 times, with an interval of 3 weeks. The injection point was located outside of the right putamen, according to a stereotactic map and preoperative magnetic resonance imaging of the monkeys. Animal health, behavior, biophysical and biochemical parameters, and brain neurological function were routinely monitored over a 6-month period posttransplantation, and the histopathologic examinations were also performed. The results showed that local pathologic damage including local tissue necrosis and inflammation was induced after the injection. The damage of low-dose and high dose groups was greater than that of the control group, yet over time, the damage could be repaired gradually. No major hMSCs-associated changes were induced from other indicators, and the transplantation of hMSCs in monkeys did not affect total immunoglobulin (Ig) M, total IgG, CD3, CD4, or CD8 values. We therefore conclude that transplantation of hMSCs to the cerebrum represents a safe alternative for clinical application of neurological disorders. PMID- 25136037 TI - Health care provider advice for adolescent tobacco use: results from the 2011 National Youth Tobacco Survey. AB - BACKGROUND: Health care providers play an important role in promoting tobacco use abstinence among adolescents. This study aimed to provide nationally representative data on the prevalence of provider tobacco use screening and advice delivered to adolescents. Cessation behaviors and correlates of past year quit attempts among current smokers are also explored. METHODS: Data came from the 2011 National Youth Tobacco Survey, a nationally representative school-based survey of adolescents in grades 6 through 12 (n = 18385). Provider screening and advice were assessed by smoking status and demographic characteristics. Logistic regression was used to assess the association between advice and past year quit attempt. RESULTS: The overall prevalence of current tobacco use was 16.6%; 10.8% were current cigarette smokers (3.6% were established smokers, 7.2% were nonestablished smokers); 17.3% were former smokers; and 71.9% were never smokers (22.6% high susceptibility, 77.4% low susceptibility). Among all respondents, the prevalence of being asked about tobacco use by a health care provider was 32.2%; the prevalence of being advised to quit or avoid tobacco was 31.4%. Established smokers were more likely than other groups to report provider assessment of tobacco use and advice. Receipt of advice was associated with a higher adjusted odds of having made a past year quit attempt (odds ratio: 1.47, 95% confidence interval: 1.18-1.82). CONCLUSIONS: Less than one-third of adolescents report being asked about tobacco use or being advised not to use tobacco. Increased tobacco use intervention by health care providers is needed to prevent initiation and increase cessation. PMID- 25136036 TI - Missed opportunities for HPV vaccination in adolescent girls: a qualitative study. AB - OBJECTIVE: The goal of this study was to identify the rationale by parents/guardians and providers for delaying or administering human papillomavirus (HPV) vaccination to girls. METHODS: Qualitative interviews were conducted with parents/guardians accompanying their vaccine-eligible 11- to 17 year-old daughters to medical visits. Interviews were conducted in 1 public clinic and 3 private practice settings to ascertain why girls did or did not receive HPV vaccination. Questions probed vaccine decision-making from the point of view of parents/guardians and providers. RESULTS: A total of 124 parents/guardians and 37 providers participated. The most common reasons parents reported for not vaccinating their daughters was the lack of a physician recommendation (44%). Both parents and providers believed that HPV vaccination provided important health benefits, but the timing of vaccination with relation to sexual activity was an important theme related to vaccine delay. Providers with lower self-reported vaccination rates delayed vaccine recommendations in girls perceived to be at low risk for sexual activity, and several parents reported that their providers suggested or supported delaying vaccination until their daughters were older. However, parents/guardians and providers agreed that predicting the timing of sexual debut was extremely difficult. In contrast, providers with high vaccination rates presented HPV vaccination as a routine vaccine with proven safety to prevent cancer, and parents responded positively to these messages. CONCLUSIONS: Although most parents and providers believe that HPV vaccination is important, missed opportunities result from assumptions about the timing of vaccination relative to sexual activity. Routinely recommending HPV vaccination as cancer prevention to be coadministered with other vaccines at age 11 years can improve vaccination rates. PMID- 25136039 TI - Pre- and postnatal exposure to parental smoking and allergic disease through adolescence. AB - OBJECTIVES: To examine the role of prenatal and postnatal second-hand tobacco smoke (SHS) exposure on asthma, rhinitis, and eczema development up to 16 years of age. METHODS: A birth cohort of 4089 children was followed for 16 years. Information on parental smoking habits, lifestyle factors, and symptoms of allergic disease was gathered using repeated parental questionnaires. Generalized estimating equations assessed the overall and age-specific associations between SHS exposure and allergic disease at ages 1 to 16 years. RESULTS: Exposure to SHS in utero was associated with an overall elevated risk of developing asthma up to 16 years (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.15-1.83) but not for rhinitis or eczema. After additional adjustment for parental smoking throughout childhood, excess overall risks for asthma remained statistically significant. Moreover, a dose-dependent pattern with SHS was observed. Exposure to SHS during infancy was associated with an overall elevated risk of asthma (OR = 1.23; 95% CI, 1.01-1.51), rhinitis (OR = 1.18; 95% CI, 1.01-1.39), and eczema (OR = 1.26; 95% CI, 1.09-1.45) up to 16 years. When age-specific associations were examined, the elevated risks related to SHS exposure in utero or during infancy were mostly confined to early childhood for asthma and rhinitis, whereas the excess risk of eczema appeared greatest at later ages. CONCLUSIONS: Our findings indicate that early SHS exposure, in utero or during infancy, influences the development of allergic disease up to adolescence. Excess risks for asthma and rhinitis were seen primarily in early childhood, whereas those for eczema occurred at later ages. PMID- 25136040 TI - HIV transmission through breastfeeding: still possible in developed countries. AB - We describe here the case of a 13-month-old boy who acquired HIV infection postnatally through breastfeeding in a developed country in 2012. His mother had regular pregnancy follow-up and was found to be seronegative for HIV on 2 consecutive screening tests (during pregnancy and just after delivery). However, 1 year later, diagnosis of HIV infection arose in both of them after a pediatric emergency department visit for bronchitis when unexplained hepatosplenomegaly and inflammatory syndrome were noted. The negative maternal viral load found just after delivery confirmed that the mother's seroconversion occurred postnatally, which allowed for active HIV transmission during lactation and lack of the efficient preventive measures that have implemented in Belgium for years. We discuss this uncommon but still existing mode of HIV transmission in industrialized countries and highlight the importance of implementing new targeted health education interventions in addition to constant clinicians' awareness. PMID- 25136041 TI - Mechanical ventilation for a child with quadriplegia. AB - Parents generally have the right to make medical decisions for their children. This right can be challenged when the parents' decision seems to go against the child's interests. The toughest such decisions are for a child who will survive with physical and neurocognitive impairments. We discuss a case of a 5-year-old boy who suffered a spinal injury as a result of a motor vehicle accident and whose father requests discontinuation of life support. Many experts recommend a "trial of therapy" to clarify both prognosis and quality of life. The key ethical question, then, is not whether to postpone a decision to forego mechanical ventilation. Instead, the key question is how long to wait. Parents should be allowed time to see what life will be like for themselves and for their child. Most of the time, life turns out better than they might have imagined. Comments are provided by 2 pediatric intensivists, Drs William Novotny and Ronald Perkin of East Carolina University, and by a specialist in rehabilitation, Dr Debjani Mukherjee of the Rehabilitation Institute of Chicago. PMID- 25136038 TI - Vaccine message framing and parents' intent to immunize their infants for MMR. AB - BACKGROUND AND OBJECTIVE: Emphasizing societal benefits of vaccines has been linked to increased vaccination intentions in adults. It is unclear if this pattern holds for parents deciding whether to vaccinate their children. The objective was to determine whether emphasizing the benefits of measles-mumps rubella (MMR) vaccination directly to the vaccine recipient or to society differentially impacts parents' vaccine intentions for their infants. METHODS: In a national online survey, parents (N = 802) of infants <12 months old were randomly assigned to receive 1 of 4 MMR vaccine messages: (1) the Centers for Disease Control and Prevention Vaccine Information Statement (VIS), (2) VIS and information emphasizing the MMR vaccine's benefits to the child, (3) VIS and information emphasizing societal benefits, or (4) VIS and information emphasizing benefits both to the child and society. Parents reported their likelihood of vaccinating their infants for MMR on a response scale of 0 (extremely unlikely) to 100 (extremely likely). RESULTS: Compared with the VIS-only group (mean intention = 86.3), parents reported increased vaccine intentions for their infants when receiving additional information emphasizing the MMR vaccine's benefits either directly to the child (mean intention = 91.6, P = .01) or to both the child and society (mean intention = 90.8, P = .03). Emphasizing the MMR vaccine's benefits only to society did not increase intentions (mean intention = 86.4, P = .97). CONCLUSIONS: We did not see increases in parents' MMR vaccine intentions for their infants when societal benefits were emphasized without mention of benefits directly to the child. This finding suggests that providers should emphasize benefits directly to the child. Mentioning societal benefits seems to neither add value to, nor interfere with, information highlighting benefits directly to the child. PMID- 25136042 TI - Neonatal vitamin K refusal and nonimmunization. AB - BACKGROUND: Neonatal Vitamin K prophylaxis is an effective intervention for reducing vitamin K deficiency bleeding. A recently published report of parental refusal of vitamin K prompted an investigation of the prevalence and characteristics of this group, and exploration of whether these same parents were likely to subsequently refuse immunization for their children. METHODS: We conducted a retrospective population-based cohort study of all infants born in Alberta between 2006 and 2012 by using linkage of administrative health data. Risk factors for vitamin K refusal were determined by using Poisson regression. The association between vitamin K refusal and nonimmunization was assessed using relative risk. RESULTS: Among the 282378 children in the cohort, 99.7% received vitamin K and 0.3% declined. Midwife-assisted deliveries were more likely to be associated with vitamin K refusal compared with physician-attended delivery (risk ratio 8.4, 95% confidence interval [CI] 6.5-11.0). Planned home delivery (risk ratio 4.9, CI 3.8-6.4) or delivery in a birth center (risk ratio 3.6, CI 2.3-5.6) were more likely to result in decline of vitamin K compared with hospital delivery. Vitamin K refusal was associated with a 14.6 (CI 13.9-15.3) higher relative risk of having no recommended childhood vaccines at 15 months. CONCLUSIONS: This is the first population-based study to characterize parents who are likely to decline vitamin K for their infants and whose children are likely to be unimmunized. These findings enable earlier identification of high-risk parents and provide an opportunity to enact strategies to increase uptake of vitamin K and childhood immunizations. PMID- 25136043 TI - Automated urinalysis and urine dipstick in the emergency evaluation of young febrile children. AB - OBJECTIVE: The performance of automated flow cytometric urinalysis is not well described in pediatric urinary tract infection. We sought to determine the diagnostic performance of automated cell counts and emergency department point-of care (POC) dipstick urinalyses in the evaluation of young febrile children. METHODS: We prospectively identified a convenience sample of febrile pediatric emergency department patients <48 months of age who underwent urethral catheterization to obtain POC and automated urinalyses and urine culture. Receiver operating characteristic analyses were performed and diagnostic indices were calculated for POC dipstick and automated cell counts at different cutpoints. RESULTS: Of 342 eligible children, 42 (12%) had urinary bacterial growth >= 50000/mL. The areas under the receiver operating characteristic curves were: automated white blood cell count, 0.97; automated bacterial count, 0.998; POC leukocyte esterase, 0.94; and POC nitrite, 0.76. Sensitivities and specificities were 86% and 98% for automated leukocyte counts >= 100/MUL and 98% and 98% for bacterial counts >= 250/MUL. POC urine dipstick with >= 1+ leukocyte esterase or positive nitrite had a sensitivity of 95% and a specificity of 98%. Combinations of white blood cell and bacterial counts did not outperform bacterial counts alone. CONCLUSIONS: Automated leukocyte and bacterial counts performed well in the diagnosis of urinary tract infection in these febrile pediatric patients, but POC dipstick may be an acceptable alternative in clinical settings that require rapid decision-making. PMID- 25136044 TI - Establishing benchmarks for the hospitalized care of children with asthma, bronchiolitis, and pneumonia. AB - BACKGROUND AND OBJECTIVES: Asthma, pneumonia, and bronchiolitis are the leading causes of admission for pediatric patients; however, the lack of accepted benchmarks is a barrier to quality improvement efforts. Using data from children hospitalized with asthma, bronchiolitis, or pneumonia, the goals of this study were to: (1) measure the 2012 performance of freestanding children's hospitals using clinical quality indicators; and (2) construct achievable benchmarks of care (ABCs) for the clinical quality indicators. METHODS: This study was a cross sectional trial using the Pediatric Health Information System database. Patient inclusions varied according to diagnosis: asthma (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 493.0-493.92) from 2 to 18 years of age; bronchiolitis (ICD-9-CM codes 466.11 and 466.19) from 2 months to 2 years of age; and pneumonia (ICD-9-CM codes 480-486, 487.0) from 2 months to 18 years of age. ABC methods use the best-performing hospitals that comprise at least 10% of the total population to compute the benchmark. RESULTS: Encounters from 42 hospitals included: asthma, 22186; bronchiolitis, 14882; and pneumonia, 12983. Asthma ABCs include: chest radiograph utilization, 24.5%; antibiotic administration, 6.6%; and ipratropium bromide use >2 days, 0%. Bronchiolitis ABCs include: chest radiograph utilization, 32.4%; viral testing, 0.6%; antibiotic administration, 18.5%; bronchodilator use >2 days, 11.4%; and steroid use, 6.4%. Pneumonia ABCs include: complete blood cell count utilization, 28.8%; viral testing, 1.5%; initial narrow-spectrum antibiotic use, 60.7%; erythrocyte sedimentation rate, 3.5%; and C-reactive protein, 0.1%. CONCLUSIONS: We report achievable benchmarks for inpatient care for asthma, bronchiolitis, and pneumonia. The establishment of national benchmarks will drive improvement at individual hospitals. PMID- 25136045 TI - Pharmacokinetics of fluoride in toddlers after application of 5% sodium fluoride dental varnish. AB - The prevalence of dental caries (tooth decay) among preschool children is increasing, driven partially by an earlier age of onset of carious lesions. The American Academy of Pediatrics recommends application of 5% sodium fluoride varnish at intervals increasing with caries risk status, as soon as teeth are present. However, the varnishes are marketed for treatment of tooth sensitivity and are regulated as medical devices rather than approved by the US Food and Drug Administration for prevention of dental caries (tooth decay). The objective of this research is to examine the safety of use in toddlers by characterizing the absorption and distribution profile of a currently marketed fluoride varnish. We measured urinary fluoride for 5 hours after application of fluoride varnish to teeth in 6 toddlers aged 12 to 15 months. Baseline levels were measured on a separate day. The urine was extracted from disposable diapers, measured by rapid diffusion, and extrapolated to plasma levels. The mean estimated plasma fluoride concentration was 13 MUg/L (SD, 9 MUg/L) during the baseline visit and 21 MUg/L (SD, 8 MUg/L) during the 5 hours after treatment. Mean estimated peak plasma fluoride after treatment was 57 MUg/L (SD, 22 MUg/L), and 20 MUg/kg (SD, 4 MUg/L) was retained on average. Retained fluoride was 253 times lower than the acute toxic dose of 5 mg/kg. Mean plasma fluoride after placement of varnish was within an SD of control levels. Occasional application of fluoride varnish following American Academy of Pediatrics guidance is safe for toddlers. PMID- 25136047 TI - Delivering tobacco control interventions in adolescent health care visits: time for action. PMID- 25136046 TI - Impact of a pertussis epidemic on infant vaccination in Washington state. AB - BACKGROUND AND OBJECTIVES: Washington State experienced a pertussis epidemic from October 2011 to December 2012. There was wide variation in incidence by county. The objectives of this study were to determine how the pertussis epidemic affected infant vaccination in Washington State and whether the incidence in counties modified this effect. METHODS: We conducted an ecologic before-after study to compare the proportion of infants up to date (UTD) with a pertussis containing vaccine at time points before (September 30, 2011), during (September 30, 2012), and after (September 30, 2013) the epidemic. Children aged 3 to 8 months enrolled in the Washington State Immunization Information System with documented county of residence were included. UTD status was determined as >= 1, >= 2, or >= 3 doses of a pertussis-containing vaccine at ages 3, 5, and 7 months, respectively. Generalized linear models with extension to the binomial family and clustered robust standard errors were used to examine differences in the proportion of UTD infants between preepidemic and either epidemic or postepidemic points. The potential modifying effect of pertussis incidence by county was examined. RESULTS: We found no significant difference in statewide UTD status with a pertussis-containing vaccine between preepidemic and either epidemic (absolute difference 2.1%; 95% confidence interval, -1.6 to 5.9) or postepidemic (absolute difference 0.2%; 95% confidence interval, -4.0 to 4.5) time points. There was no significant modification by county pertussis incidence. There was wide variation in the absolute difference in UTD status across counties. CONCLUSIONS: A statewide pertussis epidemic does not appear to have significantly changed the proportion of infants who were UTD with a pertussis-containing vaccine. PMID- 25136048 TI - High-dose vitamin A with vaccination after 6 months of age: a randomized trial. AB - BACKGROUND: The World Health Organization recommends vitamin A supplementation (VAS) at routine vaccination contacts after 6 months of age based on the assumption that it reduces mortality by 24%. The policy has never been evaluated in randomized controlled trials for its effect on overall mortality. We conducted a randomized double-blind trial to evaluate the effect of VAS with vaccines. METHODS: We randomized children aged 6 to 23 months 1:1 to VAS (100000 IU if aged 6-11 months, 200000 IU if aged 12-23 months) or placebo at vaccination contacts in Guinea-Bissau. Mortality rates were compared in Cox proportional-hazards models overall, and by gender and vaccine. RESULTS: Between August 2007 and November 2010, 7587 children were enrolled. Within 6 months of follow-up 80 nonaccident deaths occurred (VAS: 38; placebo: 42). The mortality rate ratio (MRR) comparing VAS versus placebo recipients was 0.91 (95% confidence interval 0.59-1.41) and differed significantly between boys (MRR 1.92 [0.98-3.75]) and girls (MRR 0.45 [0.24-0.87]) (P = .003 for interaction between VAS and gender). At enrollment, 42% (3161/7587) received live measles vaccine, 29% (2154/7587) received inactivated diphtheria-tetanus-pertussis-containing vaccines, and 21% (1610/7587) received both live and inactivated vaccines. The effect of VAS did not differ by vaccine group. CONCLUSIONS: This is the first randomized controlled trial to assess the effect of the policy on overall mortality. VAS had no overall effect, but the effect differed significantly by gender. More trials to ensure an optimal evidence-based vitamin A policy are warranted. PMID- 25136049 TI - Pertussis resurgence and vaccine uptake: implications for reducing vaccine hesitancy. PMID- 25136050 TI - Long-term study of a quadrivalent human papillomavirus vaccine. AB - BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine. METHODS: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6. At month 30, the placebo group (n = 482) received HPV4 vaccine following the same regimen and both cohorts were followed through month 96. Subjects >= 16 years were eligible for effectiveness evaluations. The primary objective was to evaluate the long-term anti-HPV6/11/16/18 serological levels. The secondary objective was to estimate vaccine effectiveness against HPV6/11/16/18-related persistent infection or disease. RESULTS: For each of the HPV4 vaccine types, vaccination-induced anti HPV response persisted through month 96. Among 429 subjects who received HPV4 vaccine at a mean age of 12, none developed HPV6/11/16/18-related disease or persistent infection of >= 12 months' duration. Acquisition of new sexual partners (among those >= 16 years) was ~1 per year. Subjects receiving HPV4 vaccine at month 30 (mean age 15 years) had a similar baseline rate of seropositivity to >= 1 of the 4 HPV types to those vaccinated at day 1 (mean age 12 years; 1.9% [9 of 474] vs 1.7% [20 of 1157]); however, 4 of the 9 subjects vaccinated at the later age were seropositive to 3 vaccine types, indicating previous HPV exposure. No new significant serious adverse events were observed for 8 years postvaccination in both genders. CONCLUSIONS: When administered to adolescents, the HPV4 vaccine demonstrated durability in clinically effective protection and sustained antibody titers over 8 years. PMID- 25136051 TI - Changing trends of childhood disability, 2001-2011. AB - BACKGROUND: Over the past half century the prevalence of childhood disability increased dramatically, coupled with notable increases in the prevalence of mental health and neurodevelopmental conditions. This study provides a detailed assessment of recent trends in childhood disability in relation to health conditions and sociodemographic factors. METHODS: Secondary data analysis of National Health Interview Survey (NHIS) datasets 2001-2002, 2004-2005, 2007-2008, and 2010-2011 (N = 198888) was conducted to calculate the prevalence, rate of change, severity, and sociodemographic disparities of parent-reported childhood disability. RESULTS: The prevalence of childhood disability has continued to increase, growing by 15.6% between 2001-2002 and 2010-2011. Nearly 6 million children were considered disabled in 2010-2011. Children living in poverty experienced the highest rates of disability, 102.6 cases per 1000 population in 2010-2011, but unexpectedly, children living in households with incomes >= 400% above the federal poverty level experienced the largest increase (28.4%) over this 10-year period. The percentage of disability cases related to any physical health condition declined 11.8% during the decade, whereas cases related to any neurodevelopmental or mental health condition increased by 20.9%. CONCLUSIONS: Over the past decade, parent-reported childhood disability steadily increased. As childhood disability due to physical conditions declined, there was a large increase in disabilities due to neurodevelopmental or mental health problems. For the first time since the NHIS began tracking childhood disability in 1957, the rise in reported prevalence is disproportionately occurring among socially advantaged families. This unexpected finding highlights the need to better understand the social, medical, and environmental factors influencing parent reports of childhood disability. PMID- 25136053 TI - Prevalence of human papillomavirus and Epstein-Barr virus in salivary gland diseases. AB - OBJECTIVE: The roles of human papillomavirus (HPV) and Epstein-Barr virus (EBV) in head and neck neoplasms have been well reported, but little is known about their relationship with salivary gland tumours. This study investigated the presence of HPV and EBV in salivary gland diseases. METHODS: The presence of HPV 16/18 and EBV was analysed in archival pathological specimens collected from patients who had undergone surgery for salivary gland diseases. HPV 16/18 DNA was detected using nested polymerase chain reaction (PCR) and further confirmed with immunohistochemistry. EBV DNA was detected using real-time PCR. RESULTS: A total of 61 pathological specimens were examined: 39.5% (15/38) of pleomorphic adenomas, 33.3% (3/9) of Warthin's tumours, 33.3% (one of 3) of mucoepidermoid carcinomas, and 25.0% (one of 4) of benign lymphoepithelial lesions were positive for high-risk HPV 16/18. Only two Warthin's tumours were positive for EBV. CONCLUSION: The infectious nature of salivary gland neoplasms was revealed by the high prevalence of HPV infection, and the specific presence of EBV in Warthin's tumours, suggesting a potential role for HPV and EBV in salivary gland diseases. PMID- 25136054 TI - MOG-IgG serological status matters in paediatric ADEM. PMID- 25136055 TI - The autosomal dominant spinocerebellar ataxias: emerging mechanistic themes suggest pervasive Purkinje cell vulnerability. AB - The spinocerebellar ataxias are a genetically heterogeneous group of disorders with clinically overlapping phenotypes arising from Purkinje cell degeneration, cerebellar atrophy and varying degrees of degeneration of other grey matter regions. For 22 of the 32 subtypes, a genetic cause has been identified. While recurring themes are emerging, there is no clear correlation between the clinical phenotype or penetrance, the type of genetic defect or the category of the disease mechanism, or the neuronal types involved beyond Purkinje cells. These phenomena suggest that cerebellar Purkinje cells may be a uniquely vulnerable neuronal cell type, more susceptible to a wider variety of genetic/cellular insults than most other neuron types. PMID- 25136056 TI - One-year dynamic MRI follow-up after vaginal mesh repair: evaluation of clinical, radiological, and quality-of-life results. AB - BACKGROUND: Pelvic organ prolapse (POP) is a common disorder in elderly women often surgically repaired with alloplastic meshes; yet knowledge of the pelvic floor behavior and multi-compartment defects postoperatively is scarce. PURPOSE: To evaluate the 1-year outcome after mesh repair in patients with POP using clinical examination (CE), dynamic magnetic resonance imaging (dMRI), and the prolapse quality-of-life (P-QOL) questionnaire. MATERIAL AND METHODS: A prospective observational study was conducted of 69 women undergoing pelvic mesh surgery. Clinical examination, dMRI, and the P-QOL questionnaire were applied before and after surgery to evaluate POP. Mean outcome measures were POP outcome as determined on clinical and dMRI examinations and its impact on quality of life. Statistical results were obtained with SPSS version 15.0. ANOVA was used to compare pre-/postsurgical quality of life data. RESULTS: Sixty-nine women (mean age, 64.75 years; BMI, 26.75 kg/m(2); postmenopausal, 89.2%) were recruited and treated with Seratom(r) or PerigeeTM mesh implants. A significant improvement in the position of bladder neck, vaginal vault/uterus, pouch of Douglas, and rectum was found 12 weeks and 1 year after surgery using POP-Q scale and dMRI. Advanced cystoceles and enteroceles seem underestimated by CE using the POP-Q system compared to dMRI results (P = 0.003 and P < 0.001), vice versa dMRI overestimated POP compared to CE. Sixty-four women completed the P-QOL questionnaire, presenting reduced quality of life before surgery which improves postsurgically. Prolapse impact and physical, social, and role limitations correlated strongest with a low quality of life (P < 0.001). CONCLUSION: The 1-year follow-up after mesh repair showed statistical and clinical improvement for all tools employed. dMRI seems a reliable tool for simultaneous assessment of defects in all three compartments, but tends to overestimate POP compared to clinical examination. PMID- 25136057 TI - Using party horns to test respiratory function in patients with dementia. AB - This study assessed the utility of party horns for quick, simple respiratory function testing in 66 inpatients with dementia to maintain safe eating activity. Relationships of forced vital capacity (FVC) to Mini-Mental State Examination (MMSE) score and complete extension when blowing 40- and 80-cm party horns were examined. The FVC differed significantly by both MMSE score (P = .000) and party horn score (P = .000). Significant differences in FVC were found between groups categorized by MMSE score and in groups categorized by the ability to extend both party horns. Multiple regression analyses performed on possible FVC indicators identified a significant correlation for the party horn examination (regression coefficient: .562). Breathing is always coordinated with swallowing. Party horns seem highly effective as a simple tool for testing respiratory function in patients with early-stage dementia, and the ability to offer breathing rehabilitation for patients in need is likely to result in safer eating activity. PMID- 25136058 TI - Does laboratory testing decrease during scheduled downtime of an electronic order entry system? PMID- 25136059 TI - Acute versus sub-acute care beds: should Australia invest in community beds at the expense of hospital beds? PMID- 25136060 TI - Branching out in roots: uncovering form, function, and regulation. AB - Root branching is critical for plants to secure anchorage and ensure the supply of water, minerals, and nutrients. To date, research on root branching has focused on lateral root development in young seedlings. However, many other programs of postembryonic root organogenesis exist in angiosperms. In cereal crops, the majority of the mature root system is composed of several classes of adventitious roots that include crown roots and brace roots. In this Update, we initially describe the diversity of postembryonic root forms. Next, we review recent advances in our understanding of the genes, signals, and mechanisms regulating lateral root and adventitious root branching in the plant models Arabidopsis (Arabidopsis thaliana), maize (Zea mays), and rice (Oryza sativa). While many common signals, regulatory components, and mechanisms have been identified that control the initiation, morphogenesis, and emergence of new lateral and adventitious root organs, much more remains to be done. We conclude by discussing the challenges and opportunities facing root branching research. PMID- 25136061 TI - Radial transport of nutrients: the plant root as a polarized epithelium. AB - In higher plants, roots acquire water and soil nutrients and transport them upward to their aerial parts. These functions are closely related to their anatomical structure; water and nutrients entering the root first move radially through several concentric layers of the epidermis, cortex, and endodermis before entering the central cylinder. The endodermis is the innermost cortical cell layer that features rings of hydrophobic cell wall material called the Casparian strips, which functionally resemble tight junctions in animal epithelia. Nutrient uptake from the soil can occur through three different routes that can be interconnected in various ways: the apoplastic route (through the cell wall), the symplastic route (through cellular connections), and a coupled trans-cellular route (involving polarized influx and efflux carriers). This Update presents recent advances in the radial transport of nutrients highlighting the coupled trans-cellular pathway and the roles played by the endodermis as a barrier. PMID- 25136062 TI - Distinct signaling mechanisms in multiple developmental pathways by the SCRAMBLED receptor of Arabidopsis. AB - SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase in Arabidopsis (Arabidopsis thaliana), is required for positional signaling in the root epidermis and for tissue/organ development in the shoot. To further understand SCM action, we generated a series of kinase domain variants and analyzed their ability to complement scm mutant defects. We found that the SCM kinase domain, but not kinase activity, is required for its role in root epidermal patterning, supporting the view that SCM is an atypical receptor kinase. We also describe a previously uncharacterized role for SCM in fruit dehiscence, because mature siliques from scm mutants fail to open properly. Interestingly, the kinase domain of SCM appears to be dispensable for this developmental process. Furthermore, we found that most of the SCM kinase domain mutations dramatically inhibit inflorescence development. Because this process is not affected in scm null mutants, it is likely that SCM acts redundantly to regulate inflorescence size. The importance of distinct kinase residues for these three developmental processes provides an explanation for the maintenance of the conserved kinase domain in the SCM protein, and it may generally explain its conservation in other atypical kinases. Furthermore, these results indicate that individual leucine rich repeat receptor-like kinases may participate in multiple pathways using distinct signaling mechanisms to mediate diverse cellular communication events. PMID- 25136063 TI - Activity of the brassinosteroid transcription factors BRASSINAZOLE RESISTANT1 and BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1/BRASSINAZOLE RESISTANT2 blocks developmental reprogramming in response to low phosphate availability. AB - Plants feature remarkable developmental plasticity, enabling them to respond to and cope with environmental cues, such as limited availability of phosphate, an essential macronutrient for all organisms. Under this condition, Arabidopsis (Arabidopsis thaliana) roots undergo striking morphological changes, including exhaustion of the primary meristem, impaired unidirectional cell expansion, and elevated density of lateral roots, resulting in shallow root architecture. Here, we show that the activity of two homologous brassinosteroid (BR) transcriptional effectors, BRASSINAZOLE RESISTANT1 (BZR1) and BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1 (BES1)/BZR2, blocks these responses, consequently maintaining normal root development under low phosphate conditions without impacting phosphate homeostasis. We show that phosphate deprivation shifts the intracellular localization of BES1/BZR2 to yield a lower nucleus-to-cytoplasm ratio, whereas replenishing the phosphate supply reverses this ratio within hours. Phosphate deprivation reduces the expression levels of BR biosynthesis genes and the accumulation of the bioactive BR 28-norcastasterone. In agreement, low and high BR levels sensitize and desensitize root response to this adverse condition, respectively. Hence, we propose that the environmentally controlled developmental switch from deep to shallow root architecture involves reductions in BZR1 and BES1/BZR2 levels in the nucleus, which likely play key roles in plant adaptation to phosphate-deficient environments. PMID- 25136064 TI - Efficacy of electronic cigarettes for smoking cessation. AB - OBJECTIVE: To review data demonstrating effective smoking cessation with electronic cigarettes (e-cigarettes). DATA SOURCES: A literature search of MEDLINE/PubMed (1946-March 2014) was performed using the search terms e cigarettes, electronic cigarettes, and smoking cessation. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: All English-language clinical studies assessing efficacy of e cigarettes compared with baseline, placebo, or other pharmacological methods to aid in withdrawal symptoms, smoking reduction, or cessation were evaluated. DATA SYNTHESIS: A total of 6 clinical studies were included in the review. In small studies, e-cigarettes significantly decreased desire to smoke, number of cigarettes smoked per day, and exhaled carbon monoxide levels. Symptoms of nicotine withdrawal and adverse effects were variable. The most common adverse effects were nausea, headache, cough, and mouth/throat irritation. Compared with nicotine patches, e-cigarettes were associated with fewer adverse effects and higher adherence. Most studies showed a significant decrease in cigarette use acutely; however, long-term cessation was not sustained at 6 months. CONCLUSIONS: There is limited evidence for the effectiveness of e-cigarettes in smoking cessation; however, there may be a place in therapy to help modify smoking habits or reduce the number of cigarettes smoked. Studies available provided different administration patterns such as use while smoking, instead of smoking, or as needed. Short-term studies reviewed were small and did not necessarily evaluate cessation with a focus on parameters associated with cessation withdrawal symptoms. Though long-term safety is unknown, concerns regarding increased poisoning exposures among adults in comparison with cigarettes are alarming. PMID- 25136065 TI - Albiglutide: a new GLP-1 receptor agonist for the treatment of type 2 diabetes. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of albiglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in type 2 diabetes (T2D). DATA SOURCES: A MEDLINE search (1950-June 2014) was conducted using the keyword albiglutide. References were reviewed to identify additional sources. STUDY SELECTION AND DATA EXTRACTION: Articles evaluating pharmacokinetics, pharmacodynamics, safety, or efficacy of albiglutide were included. DATA SYNTHESIS: Albiglutide is a long-acting GLP-1 RA that lowers glycosylated hemoglobin (A1C) and reduces weight by stimulating glucose-dependent insulin secretion, suppressing glucagon secretion, delaying gastric emptying, and promoting satiety. Albiglutide has a long half-life as a result of resistance to degradation by dipeptidyl peptidase-4 and fusion to albumin, thus allowing once weekly dosing. Albiglutide has been studied as monotherapy and add-on therapy to metformin, sulfonylureas, thiazolidinediones, insulin glargine, and varying combinations of these agents. Clinical studies have shown albiglutide to be superior to placebo, sitagliptin, and glimepiride and noninferior to insulin glargine and insulin lispro at reducing A1C in T2D patients, with A1C changes from baseline ranging from -0.55% to -0.9%. Noninferiority was not achieved when compared to liraglutide and pioglitazone. Weight changes ranged from +0.28 to 1.21 kg. The most common side effects are upper-respiratory-tract infections, diarrhea, nausea, and injection-site reactions. CONCLUSION: Albiglutide is the fourth GLP-1 RA approved in the United States. Advantages include once-weekly dosing and fewer gastrointestinal side effects compared with liraglutide, but it is less effective at reducing A1C and weight compared to liraglutide. It has not been compared head to head with other GLP-1 RAs. PMID- 25136068 TI - Mycoplasma hyorhinis infection promotes NF-kappaB-dependent migration of gastric cancer cells. AB - Chronic infection of Mycoplasma hyorhinis (M. hyorhinis) has been postulated to be associated with several types of cancer, but its effect on patients' survival and host factors mediating its infection remain unclear. Herein, we demonstrated that M. hyorhinis p37 protein expression in gastric cancer tissues predicts poor survival and associates with metastasis. M. hyorhinis infects mammalian cells and promotes gastric cancer cell invasiveness via its membrane protein p37. Synthesized peptide corresponding to the N-terminus of p37 prevents M. hyorhinis infection. Host Annexin A2 (ANXA2) interacts with the N-terminus of p37. In addition, EGFR forms a complex with p37 and ANXA2, and is required for M. hyorhinis-induced phosphorylation and membrane recruitment of ANXA2. M. hyorhinis infection is inhibited by siRNA-mediated knockdown of ANXA2 or EGFR, but is enhanced by expression of ectopic ANXA2 or EGFR. Downstream of ANXA2 and EGFR, the NF-kappaB pathway is activated and mediates M. hyorhinis-driven cell migration. In conclusion, our study unveils the effect of M. hyorhinis infection on gastric cancer survival and uncovers the mechanisms by which M. hyorhinis infects mammalian cells and promotes cancer cell migration. PMID- 25136067 TI - PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in breast cancer. AB - Epithelial-to-mesenchymal transition (EMT) enables metastasis. E-cadherin loss is a hallmark of EMT, but there remains an incomplete understanding of the epigenetics of this process. The protein arginine methyltransferase PRMT7 functions in various physiologic processes, including mRNA splicing, DNA repair, and neural differentiation, but its possible roles in cancer and metastasis have not been explored. In this report, we show that PRMT7 is expressed at higher levels in breast carcinoma cells and that elevated PRMT7 mediates EMT and metastasis. PRMT7 could inhibit the expression of E-cadherin by binding to its proximal promoter in a manner associated with altered histone methylation, specifically with elevated H4R3me2s and reduced H3K4me3, H3Ac, and H4Ac, which occurred at the E-cadherin promoter upon EMT induction. Moreover, PRMT7 interacted with YY1 and HDAC3 and was essential to link these proteins to the E cadherin promoter. Silencing PRMT7 restored E-cadherin expression by repressing H4R3me2s and by increasing H3K4me3 and H4Ac, attenuating cell migration and invasion in MDA-MB-231 breast cancer cells. Overall, our results define PRMT7 as an inducer of breast cancer metastasis and present the opportunity for applying PRMT7-targeted therapeutics to treat highly invasive breast cancers. PMID- 25136066 TI - AXL mediates resistance to cetuximab therapy. AB - The EGFR antibody cetuximab is used to treat numerous cancers, but intrinsic and acquired resistance to this agent is a common clinical outcome. In this study, we show that overexpression of the oncogenic receptor tyrosine kinase AXL is sufficient to mediate acquired resistance to cetuximab in models of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), where AXL was overexpressed, activated, and tightly associated with EGFR expression in cells resistant to cetuximab (Ctx(R) cells). Using RNAi methods and novel AXL targeting agents, we found that AXL activation stimulated cell proliferation, EGFR activation, and MAPK signaling in Ctx(R) cells. Notably, EGFR directly regulated the expression of AXL mRNA through MAPK signaling and the transcription factor c-Jun in Ctx(R) cells, creating a positive feedback loop that maintained EGFR activation by AXL. Cetuximab-sensitive parental cells were rendered resistant to cetuximab by stable overexpression of AXL or stimulation with EGFR ligands, the latter of which increased AXL activity and association with the EGFR. In tumor xenograft models, the development of resistance following prolonged treatment with cetuximab was associated with AXL hyperactivation and EGFR association. Furthermore, in an examination of patient-derived xenografts established from surgically resected HNSCCs, AXL was overexpressed and activated in tumors that displayed intrinsic resistance to cetuximab. Collectively, our results identify AXL as a key mediator of cetuximab resistance, providing a rationale for clinical evaluation of AXL-targeting drugs to treat cetuximab resistant cancers. Cancer Res; 74(18); 5152-64. (c)2014 AACR. PMID- 25136069 TI - Epigenetic states of cells of origin and tumor evolution drive tumor-initiating cell phenotype and tumor heterogeneity. AB - A central confounding factor in the development of targeted therapies is tumor cell heterogeneity, particularly in tumor-initiating cells (TIC), within clinically identical tumors. Here, we show how activation of the Sonic Hedgehog (SHH) pathway in neural stem and progenitor cells creates a foundation for tumor cell evolution to heterogeneous states that are histologically indistinguishable but molecularly distinct. In spontaneous medulloblastomas that arise in Patched (Ptch)(+/-) mice, we identified three distinct tumor subtypes. Through cell type specific activation of the SHH pathway in vivo, we determined that different cells of origin evolved in unique ways to generate these subtypes. Moreover, TICs in each subtype had distinct molecular and cellular phenotypes. At the bulk tumor level, the three tumor subtypes could be distinguished by a 465-gene signature and by differential activation levels of the ERK and AKT pathways. Notably, TICs from different subtypes were differentially sensitive to SHH or AKT pathway inhibitors, highlighting new mechanisms of resistance to targeted therapies. In summary, our results show how evolutionary processes act on distinct cells of origin to contribute to tumoral heterogeneity, at both bulk tumor and TIC levels. PMID- 25136072 TI - Proposal for a synthetic lethality therapy using the paralog dependence of cancer cells--response. PMID- 25136070 TI - ACVR1 mutations in DIPG: lessons learned from FOP. AB - Whole-genome sequencing studies have recently identified a quarter of cases of the rare childhood brainstem tumor diffuse intrinsic pontine glioma to harbor somatic mutations in ACVR1. This gene encodes the type I bone morphogenic protein receptor ALK2, with the residues affected identical to those that, when mutated in the germline, give rise to the congenital malformation syndrome fibrodysplasia ossificans progressiva (FOP), resulting in the transformation of soft tissue into bone. This unexpected link points toward the importance of developmental biology processes in tumorigenesis and provides an extensive experience in mechanistic understanding and drug development hard-won by FOP researchers to pediatric neurooncology. Here, we review the literature in both fields and identify potential areas for collaboration and rapid advancement for patients of both diseases. PMID- 25136073 TI - A synthetic lethality-based strategy to treat cancers harboring a genetic deficiency in the chromatin remodeling factor BRG1--letter. PMID- 25136075 TI - Mouse models of human cancer. AB - The Helmholtz Alliance Preclinical Comprehensive Cancer Center (PCCC; www.helmholtz-pccc.de) hosted the "1st International Kloster Seeon Meeting on Mouse Models of Human Cancer" in the Seeon monastery (Germany) from March 8 to 11, 2014. The meeting focused on the development and application of novel mouse models in tumor research and high-throughput technologies to overcome one of the most critical bottlenecks in translational bench-to-bedside tumor biology research. Moreover, the participants discussed basic molecular mechanisms underlying tumor initiation, progression, metastasis, and therapy resistance, which are the prerequisite for the development of novel treatment strategies and clinical applications in cancer therapy. PMID- 25136076 TI - Correlates and prognosis of early recurrence after catheter ablation for ventricular tachycardia due to structural heart disease. AB - BACKGROUND: Catheter ablation for ventricular tachycardia (VT) from structural heart disease has a significant risk of recurrence, but the optimal duration for in-hospital monitoring is not defined. This study assesses the timing, correlates, and prognostic significance of early VT recurrence after ablation. METHODS AND RESULTS: Of 370 patients (313 men; aged 63.0+/-13.2 years) who underwent a first radiofrequency ablation for sustained monomorphic VT associated with structural heart disease from 2008 to 2012, sustained VT recurred in 81 patients (22%) within 7 days. In multivariable analysis, early recurrence was associated with New York Heart Association classification >=III (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.03-3.48; P=0.04), dilated cardiomyopathy (OR 1.93, 95% CI 1.03-3.57; P=0.04), prevalence of VT storm before the procedure (OR 2.62, 95% CI 1.48-4.65; P=0.001), a greater number of induced VTs (OR 1.24, 95% CI 1.07-1.45; P=0.006), and acute failure or no final induction test (OR 1.88, 95% CI 1.03-3.40; P=0.04). During a median of 2.5 (1.2, 4.0) years of follow-up, early VT recurrence was an independent correlates of mortality (hazard ratio 2.59, 95% CI 1.52-4.34; P=0.0005). CONCLUSIONS: Patients who have early recurrences of VT after ablation are a high risk group who may be identifiable from their clinical profile. Further study is warranted to define the optimal treatment strategies for this patient group. PMID- 25136077 TI - Mortality reduction in relation to implantable cardioverter defibrillator programming in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). AB - BACKGROUND: The benefit of novel implantable cardioverter defibrillator (ICD) programming in reducing inappropriate ICD therapy and mortality was demonstrated in Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT). However, the cause of mortality reduction remains incompletely evaluated. We aimed to identify factors associated with mortality, with focus on ICD therapy and programming in the MADIT-RIT population. METHODS AND RESULTS: In MADIT-RIT, 1500 patients with a primary prophylactic indication for ICD or cardiac resynchronization therapy with defibrillator were randomized to 1 of 3 different ICD programming arms: conventional programming (ventricular tachycardia zone >=170 beats per minute), high-rate programming (ventricular tachycardia zone >=200 beats per minute), and delayed programming (60-second delay before therapy >=170 beats per minute). Multivariate Cox models were used to assess the influence of time-dependent appropriate and inappropriate ICD therapy (shock and antitachycardia pacing) and randomized programming arm on all cause mortality. During an average follow-up of 1.4+/-0.6 years, 71 of 1500 (5%) patients died: cardiac in 40 patients (56.3%), noncardiac in 23 patients (32.4%), and unknown in 8 patients (11.3%). Appropriate shocks (hazard ratio, 6.32; 95% confidence interval, 3.13-12.75; P<0.001) and inappropriate therapy (hazard ratio, 2.61; 95% confidence interval, 1.28-5.31; P=0.01) were significantly associated with an increased mortality risk. There was no evidence of increased mortality risk in patients who experienced appropriate antitachycardia pacing only (hazard ratio, 1.02; 95% confidence interval, 0.36-2.88; P=0.98). Randomization to conventional programming was identified as an independent predictor of death when compared with patients randomized to high-rate programming (hazard ratio, 2.0; 95% confidence interval, 1.06-3.71; P=0.03). CONCLUSIONS: In MADIT-RIT, appropriate shocks, inappropriate ICD therapy, and randomization to conventional ICD programming were independently associated with an increased mortality risk. Appropriate antitachycardia pacing was not related to an adverse outcome. CLINICAL TRIAL REGISTRATION URL: clinicaltrials.gov Unique identifier: NCT00947310. PMID- 25136081 TI - Therapeutic exercise for chronic non-specific neck pain: PEDro systematic review update. PMID- 25136078 TI - Detailed analysis of bone marrow from patients with ischemic heart disease and left ventricular dysfunction: BM CD34, CD11b, and clonogenic capacity as biomarkers for clinical outcomes. AB - RATIONALE: Bone marrow (BM) cell therapy for ischemic heart disease (IHD) has shown mixed results. Before the full potency of BM cell therapy can be realized, it is essential to understand the BM niche after acute myocardial infarction (AMI). OBJECTIVE: To study the BM composition in patients with IHD and severe left ventricular (LV) dysfunction. METHODS AND RESULTS: BM from 280 patients with IHD and LV dysfunction were analyzed for cell subsets by flow cytometry and colony assays. BM CD34(+) cell percentage was decreased 7 days after AMI (mean of 1.9% versus 2.3%-2.7% in other cohorts; P<0.05). BM-derived endothelial colonies were significantly decreased (P<0.05). Increased BM CD11b(+) cells associated with worse LV ejection fraction (LVEF) after AMI (P<0.05). Increased BM CD34(+) percentage associated with greater improvement in LVEF (+9.9% versus +2.3%; P=0.03, for patients with AMI and +6.6% versus -0.02%; P=0.021 for patients with chronic IHD). In addition, decreased BM CD34(+) percentage in patients with chronic IHD correlated with decrement in LVEF (-2.9% versus +0.7%; P=0.0355). CONCLUSIONS: In this study, we show a heterogeneous mixture of BM cell subsets, decreased endothelial colony capacity, a CD34+ cell nadir 7 days after AMI, a negative correlation between CD11b percentage and postinfarct LVEF, and positive correlation of CD34 percentage with change in LVEF after cell therapy. These results serve as a possible basis for the small clinical improvement seen in autologous BM cell therapy trials and support selection of potent cell subsets and reversal of comorbid BM impairment. CLINICAL TRIAL REGISTRATIONS URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00684021, NCT00684060, and NCT00824005. PMID- 25136080 TI - Incidence of periorbital necrotising fasciitis in the UK population: a BOSU study. AB - BACKGROUND: Periorbital necrotising fasciitis (PNF) is a devastating infection of subcutaneous soft tissue and underlying fascia causing severe morbidity and even loss of life. Few case reports of PNF exist and there are no prospective epidemiological studies. METHODS: A prospective observational study was undertaken using the British Ophthalmological Surveillance Unit reporting system. Questionnaires were sent to reporting ophthalmologists in the UK seeking cases of PNF over a 2-year period. RESULTS: 30 new cases were confirmed. 16 of the reported cases followed a precipitating event, 9 cases followed trauma and 3 followed surgery. beta-haemolytic Streptococcus A was the causative organism identified in 76%, either alone or with concurrent infection, and antibiotic sensitivities are discussed. Systemic complications occurred in the majority of cases (66.6%), with sepsis and death occurring in 10%. Over 50% of surviving patients had subsequent morbidity, reduced acuity (<6/18) being common. CONCLUSION: PNF is a rare, dangerous condition. This study identified an incidence of 0.24 per 1,000,000 per annum in the UK. beta-haemolytic Streptococcus A is the most common causative organism. Mortality remains a potential outcome, and survivors suffer significant morbidity. Early intravenous antibiotic management with a consensus favouring penicillin and clindamycin combined with debridement. PMID- 25136082 TI - Physiotherapy improves eating disorders and quality of life in bulimia and anorexia nervosa. PMID- 25136079 TI - Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). AB - Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due to the exponential increase in life expectancy and environmental risks. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies in medicine. The wide introduction of anti-VEGF therapy has led to an overwhelming improvement in the prognosis of patients affected by neovascular AMD, allowing recovery and maintenance of visual function in the vast majority of patients. However, the therapeutic benefit is accompanied by significant economic investments, unresolved medicolegal debates about the use of off-label substances and overwhelming problems in large population management. The burden of disease has turned into a burden of care with a dissociation of scientific advances and real-world clinical performance. Simultaneously, ground breaking innovations in diagnostic technologies, such as optical coherence tomography, allows unprecedented high-resolution visualisation of disease morphology and provides a promising horizon for early disease detection and efficient therapeutic follow-up. However, definite conclusions from morphologic parameters are still lacking, and valid biomarkers have yet to be identified to provide a practical base for disease management. The European Society of Retina Specialists offers expert guidance for diagnostic and therapeutic management of neovascular AMD supporting healthcare givers and doctors in providing the best state-of-the-art care to their patients. TRIAL REGISTRATION NUMBER: NCT01318941. PMID- 25136084 TI - Effect of woody-plant encroachment on livestock production in North and South America. AB - A large fraction of the world grasslands and savannas are undergoing a rapid shift from herbaceous to woody-plant dominance. This land-cover change is expected to lead to a loss in livestock production (LP), but the impacts of woody plant encroachment on this crucial ecosystem service have not been assessed. We evaluate how tree cover (TC) has affected LP at large spatial scales in rangelands of contrasting social-economic characteristics in the United States and Argentina. Our models indicate that in areas of high productivity, a 1% increase in TC results in a reduction in LP ranging from 0.6 to 1.6 reproductive cows (Rc) per km(2). Mean LP in the United States is 27 Rc per km(2), so a 1% increase in TC results in a 2.5% decrease in mean LP. This effect is large considering that woody-plant cover has been described as increasing at 0.5% to 2% per y. On the contrary, in areas of low productivity, increased TC had a positive effect on LP. Our results also show that ecological factors account for a larger fraction of LP variability in Argentinean than in US rangelands. Differences in the relative importance of ecological versus nonecological drivers of LP in Argentina and the United States suggest that the valuation of ecosystem services between these two rangelands might be different. Current management strategies in Argentina are likely designed to maximize LP for various reasons we are unable to explore in this effort, whereas land managers in the United States may be optimizing multiple ecosystem services, including conservation or recreation, alongside LP. PMID- 25136083 TI - TIM-family proteins inhibit HIV-1 release. AB - Accumulating evidence indicates that T-cell immunoglobulin (Ig) and mucin domain (TIM) proteins play critical roles in viral infections. Herein, we report that the TIM-family proteins strongly inhibit HIV-1 release, resulting in diminished viral production and replication. Expression of TIM-1 causes HIV-1 Gag and mature viral particles to accumulate on the plasma membrane. Mutation of the phosphatidylserine (PS) binding sites of TIM-1 abolishes its ability to block HIV 1 release. TIM-1, but to a much lesser extent PS-binding deficient mutants, induces PS flipping onto the cell surface; TIM-1 is also found to be incorporated into HIV-1 virions. Importantly, TIM-1 inhibits HIV-1 replication in CD4-positive Jurkat cells, despite its capability of up-regulating CD4 and promoting HIV-1 entry. In addition to TIM-1, TIM-3 and TIM-4 also block the release of HIV-1, as well as that of murine leukemia virus (MLV) and Ebola virus (EBOV); knockdown of TIM-3 in differentiated monocyte-derived macrophages (MDMs) enhances HIV-1 production. The inhibitory effects of TIM-family proteins on virus release are extended to other PS receptors, such as Axl and RAGE. Overall, our study uncovers a novel ability of TIM-family proteins to block the release of HIV-1 and other viruses by interaction with virion- and cell-associated PS. Our work provides new insights into a virus-cell interaction that is mediated by TIMs and PS receptors. PMID- 25136086 TI - Development of in-group favoritism in children's third-party punishment of selfishness. AB - When enforcing norms for cooperative behavior, human adults sometimes exhibit in group bias. For example, third-party observers punish selfish behaviors committed by out-group members more harshly than similar behaviors committed by in-group members. Although evidence suggests that children begin to systematically punish selfish behavior around the age of 6 y, the development of in-group bias in their punishment remains unknown. Do children start off enforcing fairness norms impartially, or is norm enforcement biased from its emergence? How does bias change over development? Here, we created novel social groups in the laboratory and gave 6- and 8-year-olds the opportunity to engage in costly third-party punishment of selfish sharing behavior. We found that by age 6, punishment was already biased: Selfish resource allocations received more punishment when they were proposed by out-group members and when they disadvantaged in-group members. We also found that although costly punishment increased between ages 6 and 8, bias in punishment partially decreased. Although 8-y-olds also punished selfish out-group members more harshly, they were equally likely to punish on behalf of disadvantaged in-group and out-group members, perhaps reflecting efforts to enforce norms impartially. Taken together, our results suggest that norm enforcement is biased from its emergence, but that this bias can be partially overcome through developmental change. PMID- 25136085 TI - Narcolepsy patients have antibodies that stain distinct cell populations in rat brain and influence sleep patterns. AB - Narcolepsy is a chronic sleep disorder, likely with an autoimmune component. During 2009 and 2010, a link between A(H1N1)pdm09 Pandemrix vaccination and onset of narcolepsy was suggested in Scandinavia. In this study, we searched for autoantibodies related to narcolepsy using a neuroanatomical array: rat brain sections were processed for immunohistochemistry/double labeling using patient sera/cerebrospinal fluid as primary antibodies. Sera from 89 narcoleptic patients, 52 patients with other sleep-related disorders (OSRDs), and 137 healthy controls were examined. Three distinct patterns of immunoreactivity were of particular interest: pattern A, hypothalamic melanin-concentrating hormone and proopiomelanocortin but not hypocretin/orexin neurons; pattern B, GABAergic cortical interneurons; and pattern C, mainly globus pallidus neurons. Altogether, 24 of 89 (27%) narcoleptics exhibited pattern A or B or C. None of the patterns were exclusive for narcolepsy but were also detected in the OSRD group at significantly lower numbers. Also, some healthy controls exhibited these patterns. The antigen of pattern A autoantibodies was identified as the common C terminal epitope of neuropeptide glutamic acid-isoleucine/alpha-melanocyte stimulating hormone (NEI/alphaMSH) peptides. Passive transfer experiments on rat showed significant effects of pattern A human IgGs on rapid eye movement and slow wave sleep time parameters in the inactive phase and EEG theta-power in the active phase. We suggest that NEI/alphaMSH autoantibodies may interfere with the fine regulation of sleep, contributing to the complex pathogenesis of narcolepsy and OSRDs. Also, patterns B and C are potentially interesting, because recent data suggest a relevance of those brain regions/neuron populations in the regulation of sleep/arousal. PMID- 25136087 TI - Fluvial network organization imprints on microbial co-occurrence networks. AB - Recent studies highlight linkages among the architecture of ecological networks, their persistence facing environmental disturbance, and the related patterns of biodiversity. A hitherto unresolved question is whether the structure of the landscape inhabited by organisms leaves an imprint on their ecological networks. We analyzed, based on pyrosequencing profiling of the biofilm communities in 114 streams, how features inherent to fluvial networks affect the co-occurrence networks that the microorganisms form in these biofilms. Our findings suggest that hydrology and metacommunity dynamics, both changing predictably across fluvial networks, affect the fragmentation of the microbial co-occurrence networks throughout the fluvial network. The loss of taxa from co-occurrence networks demonstrates that the removal of gatekeepers disproportionately contributed to network fragmentation, which has potential implications for the functions biofilms fulfill in stream ecosystems. Our findings are critical because of increased anthropogenic pressures deteriorating stream ecosystem integrity and biodiversity. PMID- 25136089 TI - Vaccines against poverty. AB - With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID- 25136088 TI - Introgression in hybrid ants is favored in females but selected against in males. AB - Hybridization is not a mere reproductive dead end but has been suggested to play a central role in speciation, for example, by introducing adaptive genetic variation. Our previous study uncovered a unique consequence of hybridization in Formica ants. In a population including two isolated but partially introgressed genetic groups, the females have an apparent hybrid background, whereas the males do not. This situation results in large-scale differences between male and female genomes that are stable throughout generations. Here, we compare genotypes from different developmental stages to investigate how sex-specific introgression and genetic differences between sexes are maintained. We show that strong selection rather than sex-dependent transmission maintains the genetic differences between sexes. All genotype combinations are produced and observed in the eggs of both sexes, but the alleles acquired through hybridization disappear from the haploid males during development from egg to adult as their frequencies drop toward zero. However, the same introgressed alleles increase in frequency and are favored when heterozygous in the females. Genotypes eliminated from males most likely represent incompatibilities arising from hybridization. Our results show an unusual situation of opposite selection, where introgression is favored in diploid females but selected against in haploid males. This finding suggests that introgressed genomic regions harbor both fitness-enhancing and -reducing elements. Our work highlights the complex consequences of hybridization and provides a rare opportunity to observe natural selection in real time in nature. PMID- 25136090 TI - Climate change poised to threaten hydrologic connectivity and endemic fishes in dryland streams. AB - Protecting hydrologic connectivity of freshwater ecosystems is fundamental to ensuring species persistence, ecosystem integrity, and human well-being. More frequent and severe droughts associated with climate change are poised to significantly alter flow intermittence patterns and hydrologic connectivity in dryland streams of the American Southwest, with deleterious effects on highly endangered fishes. By integrating local-scale hydrologic modeling with emerging approaches in landscape ecology, we quantify fine-resolution, watershed-scale changes in habitat size, spacing, and connectance under forecasted climate change in the Verde River Basin, United States. Model simulations project annual zero flow day frequency to increase by 27% by midcentury, with differential seasonal consequences on continuity (temporal continuity at discrete locations) and connectivity (spatial continuity within the network). A 17% increase in the frequency of stream drying events is expected throughout the network with associated increases in the duration of these events. Flowing portions of the river network will diminish between 8% and 20% in spring and early summer and become increasingly isolated by more frequent and longer stretches of dry channel fragments, thus limiting the opportunity for native fishes to access spawning habitats and seasonally available refuges. Model predictions suggest that midcentury and late century climate will reduce network-wide hydrologic connectivity for native fishes by 6-9% over the course of a year and up to 12-18% during spring spawning months. Our work quantifies climate-induced shifts in stream drying and connectivity across a large river network and demonstrates their implications for the persistence of a globally endemic fish fauna. PMID- 25136091 TI - Reconstruction of scalar and vectorial components in X-ray dark-field tomography. AB - Grating-based X-ray dark-field imaging is a novel technique for obtaining image contrast for object structures at size scales below setup resolution. Such an approach appears particularly beneficial for medical imaging and nondestructive testing. It has already been shown that the dark-field signal depends on the direction of observation. However, up to now, algorithms for fully recovering the orientation dependence in a tomographic volume are still unexplored. In this publication, we propose a reconstruction method for grating-based X-ray dark field tomography, which models the orientation-dependent signal as an additional observable from a standard tomographic scan. In detail, we extend the tomographic volume to a tensorial set of voxel data, containing the local orientation and contributions to dark-field scattering. In our experiments, we present the first results of several test specimens exhibiting a heterogeneous composition in microstructure, which demonstrates the diagnostic potential of the method. PMID- 25136092 TI - Protein crystal structure obtained at 2.9 A resolution from injecting bacterial cells into an X-ray free-electron laser beam. AB - It has long been known that toxins produced by Bacillus thuringiensis (Bt) are stored in the bacterial cells in crystalline form. Here we describe the structure determination of the Cry3A toxin found naturally crystallized within Bt cells. When whole Bt cells were streamed into an X-ray free-electron laser beam we found that scattering from other cell components did not obscure diffraction from the crystals. The resolution limits of the best diffraction images collected from cells were the same as from isolated crystals. The integrity of the cells at the moment of diffraction is unclear; however, given the short time (~ 5 us) between exiting the injector to intersecting with the X-ray beam, our result is a 2.9-A resolution structure of a crystalline protein as it exists in a living cell. The study suggests that authentic in vivo diffraction studies can produce atomic level structural information. PMID- 25136093 TI - Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction. AB - Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID- 25136094 TI - Adaptive optoelectronic camouflage systems with designs inspired by cephalopod skins. AB - Octopus, squid, cuttlefish, and other cephalopods exhibit exceptional capabilities for visually adapting to or differentiating from the coloration and texture of their surroundings, for the purpose of concealment, communication, predation, and reproduction. Long-standing interest in and emerging understanding of the underlying ultrastructure, physiological control, and photonic interactions has recently led to efforts in the construction of artificial systems that have key attributes found in the skins of these organisms. Despite several promising options in active materials for mimicking biological color tuning, existing routes to integrated systems do not include critical capabilities in distributed sensing and actuation. Research described here represents progress in this direction, demonstrated through the construction, experimental study, and computational modeling of materials, device elements, and integration schemes for cephalopod-inspired flexible sheets that can autonomously sense and adapt to the coloration of their surroundings. These systems combine high-performance, multiplexed arrays of actuators and photodetectors in laminated, multilayer configurations on flexible substrates, with overlaid arrangements of pixelated, color-changing elements. The concepts provide realistic routes to thin sheets that can be conformally wrapped onto solid objects to modulate their visual appearance, with potential relevance to consumer, industrial, and military applications. PMID- 25136096 TI - Pseudomonas aeruginosa triggers CFTR-mediated airway surface liquid secretion in swine trachea. AB - Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the gene encoding for the anion channel cystic fibrosis transmembrane conductance regulator (CFTR). Several organs are affected in CF, but most of the morbidity and mortality comes from lung disease. Recent data show that the initial consequence of CFTR mutation is the failure to eradicate bacteria before the development of inflammation and airway remodeling. Bacterial clearance depends on a layer of airway surface liquid (ASL) consisting of both a mucus layer that traps, kills, and inactivates bacteria and a periciliary liquid layer that keeps the mucus at an optimum distance from the underlying epithelia, to maximize ciliary motility and clearance of bacteria. The airways in CF patients and animal models of CF demonstrate abnormal ASL secretion and reduced antimicrobial properties. Thus, it has been proposed that abnormal ASL secretion in response to bacteria may facilitate the development of the infection and inflammation that characterize CF airway disease. Whether the inhalation of bacteria triggers ASL secretion, and the role of CFTR, have never been tested, however. We developed a synchrotron-based imaging technique to visualize the ASL layer and measure the effect of bacteria on ASL secretion. We show that the introduction of Pseudomonas aeruginosa and other bacteria into the lumen of intact isolated swine tracheas triggers CFTR-dependent ASL secretion by the submucosal glands. This response requires expression of the bacterial protein flagellin. In patients with CF, the inhalation of bacteria would fail to trigger ASL secretion, leading to infection and inflammation. PMID- 25136097 TI - Submesoscale dispersion in the vicinity of the Deepwater Horizon spill. AB - Reliable forecasts for the dispersion of oceanic contamination are important for coastal ecosystems, society, and the economy as evidenced by the Deepwater Horizon oil spill in the Gulf of Mexico in 2010 and the Fukushima nuclear plant incident in the Pacific Ocean in 2011. Accurate prediction of pollutant pathways and concentrations at the ocean surface requires understanding ocean dynamics over a broad range of spatial scales. Fundamental questions concerning the structure of the velocity field at the submesoscales (100 m to tens of kilometers, hours to days) remain unresolved due to a lack of synoptic measurements at these scales. Using high-frequency position data provided by the near-simultaneous release of hundreds of accurately tracked surface drifters, we study the structure of submesoscale surface velocity fluctuations in the Northern Gulf of Mexico. Observed two-point statistics confirm the accuracy of classic turbulence scaling laws at 200-m to 50-km scales and clearly indicate that dispersion at the submesoscales is local, driven predominantly by energetic submesoscale fluctuations. The results demonstrate the feasibility and utility of deploying large clusters of drifting instruments to provide synoptic observations of spatial variability of the ocean surface velocity field. Our findings allow quantification of the submesoscale-driven dispersion missing in current operational circulation models and satellite altimeter-derived velocity fields. PMID- 25136095 TI - Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice. AB - Psoriasis (Ps) and psoriasis arthritis (PsA) are poorly understood common diseases, induced by unknown environmental factors, affecting skin and articular joints. A single i.p. exposure to mannan from Saccharomyces cerevisiae induced an acute inflammation in inbred mouse strains resembling human Ps and PsA-like disease, whereas multiple injections induced a relapsing disease. Exacerbation of disease severity was observed in mice deficient for generation of reactive oxygen species (ROS). Interestingly, restoration of ROS production, specifically in macrophages, ameliorated both skin and joint disease. Neutralization of IL-17A, mainly produced by gammadelta T cells, completely blocked disease symptoms. Furthermore, mice depleted of granulocytes were resistant to disease development. In contrast, certain acute inflammatory mediators (C5, Fcgamma receptor III, mast cells, and histamine) and adaptive immune players (alphabeta T and B cells) were redundant in disease induction. Hence, we propose that mannan-induced activation of macrophages leads to TNF-alpha secretion and stimulation of local gammadelta T cells secreting IL-17A. The combined action of activated macrophages and IL-17A produced in situ drives neutrophil infiltration in the epidermis and dermis of the skin, leading to disease manifestations. Thus, our finding suggests a new mechanism triggered by exposure to exogenous microbial components, such as mannan, that can induce and exacerbate Ps and PsA. PMID- 25136098 TI - UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation. AB - Histone H2B monoubiquitylation plays an important role in RNA polymerase II (RNAPII) elongation. Whether this modification responds to RNAPII stalling is not yet known. We report that both yeast and human cells undergo a rapid and significant H2B deubiquitylation after exposure to UV irradiation. This deubiquitylation occurs concurrently with UV-induced transcription arrest and is significantly reduced in a DNA damage-bypassing RNAPII yeast mutant. Consistent with these results, yeast deubiquitylases Ubp8 and Ubp10 are associated with the RNAPII complex. Moreover, simultaneous deletion of Ubp8 and Ubp10 leads to a lack of H2B deubiquitylation after UV exposure. Consequently, nucleotide excision repair at an actively transcribed gene locus is decreased, whereas UV-induced RNAPII degradation is increased in ubp8Deltaubp10Delta mutant cells. These results indicate that eukaryotic cells respond to RNAPII arrest by deubiquitylating H2B to coordinate DNA repair and RNAPII degradation. PMID- 25136099 TI - Gyrification from constrained cortical expansion. AB - The exterior of the mammalian brain--the cerebral cortex--has a conserved layered structure whose thickness varies little across species. However, selection pressures over evolutionary time scales have led to cortices that have a large surface area to volume ratio in some organisms, with the result that the brain is strongly convoluted into sulci and gyri. Here we show that the gyrification can arise as a nonlinear consequence of a simple mechanical instability driven by tangential expansion of the gray matter constrained by the white matter. A physical mimic of the process using a layered swelling gel captures the essence of the mechanism, and numerical simulations of the brain treated as a soft solid lead to the formation of cusped sulci and smooth gyri similar to those in the brain. The resulting gyrification patterns are a function of relative cortical expansion and relative thickness (compared with brain size), and are consistent with observations of a wide range of brains, ranging from smooth to highly convoluted. Furthermore, this dependence on two simple geometric parameters that characterize the brain also allows us to qualitatively explain how variations in these parameters lead to anatomical anomalies in such situations as polymicrogyria, pachygyria, and lissencephalia. PMID- 25136100 TI - Label-free probe of HIV-1 TAT peptide binding to mimetic membranes. AB - The transacting activator of transduction (TAT) protein plays a key role in the progression of AIDS. Studies have shown that a +8 charged sequence of amino acids in the protein, called the TAT peptide, enables the TAT protein to penetrate cell membranes. To probe mechanisms of binding and translocation of the TAT peptide into the cell, investigators have used phospholipid liposomes as cell membrane mimics. We have used the method of surface potential sensitive second harmonic generation (SHG), which is a label-free and interface-selective method, to study the binding of TAT to anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-1'-rac glycerol (POPG) and neutral 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes. It is the SHG sensitivity to the electrostatic field generated by a charged interface that enabled us to obtain the interfacial electrostatic potential. SHG together with the Poisson-Boltzmann equation yielded the dependence of the surface potential on the density of adsorbed TAT. We obtained the dissociation constants Kd for TAT binding to POPC and POPG liposomes and the maximum number of TATs that can bind to a given liposome surface. For POPC Kd was found to be 7.5 +/- 2 MUM, and for POPG Kd was 29.0 +/- 4.0 MUM. As TAT was added to the liposome solution the POPC surface potential changed from 0 mV to +37 mV, and for POPG it changed from -57 mV to -37 mV. A numerical calculation of Kd, which included all terms obtained from application of the Poisson-Boltzmann equation to the TAT liposome SHG data, was shown to be in good agreement with an approximated solution. PMID- 25136101 TI - Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter gatherers. AB - The evolutionary history of the human pygmy phenotype (small body size), a characteristic of African and Southeast Asian rainforest hunter-gatherers, is largely unknown. Here we use a genome-wide admixture mapping analysis to identify 16 genomic regions that are significantly associated with the pygmy phenotype in the Batwa, a rainforest hunter-gatherer population from Uganda (east central Africa). The identified genomic regions have multiple attributes that provide supporting evidence of genuine association with the pygmy phenotype, including enrichments for SNPs previously associated with stature variation in Europeans and for genes with growth hormone receptor and regulation functions. To test adaptive evolutionary hypotheses, we computed the haplotype-based integrated haplotype score (iHS) statistic and the level of population differentiation (FST) between the Batwa and their agricultural neighbors, the Bakiga, for each genomic SNP. Both |iHS| and FST values were significantly higher for SNPs within the Batwa pygmy phenotype-associated regions than the remainder of the genome, a signature of polygenic adaptation. In contrast, when we expanded our analysis to include Baka rainforest hunter-gatherers from Cameroon and Gabon (west central Africa) and Nzebi and Nzime neighboring agriculturalists, we did not observe elevated |iHS| or FST values in these genomic regions. Together, these results suggest adaptive and at least partially convergent origins of the pygmy phenotype even within Africa, supporting the hypothesis that small body size confers a selective advantage for tropical rainforest hunter-gatherers but raising questions about the antiquity of this behavior. PMID- 25136102 TI - Systems vaccinology: probing humanity's diverse immune systems with vaccines. AB - Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic changes during the past century have created further diversification with respect to age, nutritional status, and the incidence of associated chronic inflammatory disorders and chronic infections. These shifting demographics pose new challenges for vaccination, as emerging evidence suggests that age, the metabolic state, and chronic infections can exert major influences on the immune system. Thus, a key public health challenge is learning how to reprogram suboptimal immune systems to induce effective vaccine immunity. Recent advances have applied systems biological analysis to define molecular signatures induced early after vaccination that correlate with and predict the later adaptive immune responses in humans. Such "systems vaccinology" approaches offer an integrated picture of the molecular networks driving vaccine immunity, and are beginning to yield novel insights about the immune system. Here we discuss the promise of systems vaccinology in probing humanity's diverse immune systems, and in delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. Such insights will be critical in reengineering suboptimal immune systems in immunocompromised populations. PMID- 25136103 TI - Genetic and pharmacological reactivation of the mammalian inactive X chromosome. AB - X-chromosome inactivation (XCI), the random transcriptional silencing of one X chromosome in somatic cells of female mammals, is a mechanism that ensures equal expression of X-linked genes in both sexes. XCI is initiated in cis by the noncoding Xist RNA, which coats the inactive X chromosome (Xi) from which it is produced. However, trans-acting factors that mediate XCI remain largely unknown. Here, we perform a large-scale RNA interference screen to identify trans-acting XCI factors (XCIFs) that comprise regulators of cell signaling and transcription, including the DNA methyltransferase, DNMT1. The expression pattern of the XCIFs explains the selective onset of XCI following differentiation. The XCIFs function, at least in part, by promoting expression and/or localization of Xist to the Xi. Surprisingly, we find that DNMT1, which is generally a transcriptional repressor, is an activator of Xist transcription. Small-molecule inhibitors of two of the XCIFs can reversibly reactivate the Xi, which has implications for treatment of Rett syndrome and other dominant X-linked diseases. A homozygous mouse knockout of one of the XCIFs, stanniocalcin 1 (STC1), has an expected XCI defect but surprisingly is phenotypically normal. Remarkably, X-linked genes are not overexpressed in female Stc1(-/-) mice, revealing the existence of a mechanism(s) that can compensate for a persistent XCI deficiency to regulate X linked gene expression. PMID- 25136106 TI - QnAs with Patricia Kuhl. PMID- 25136104 TI - Direct measurement of the dielectric polarization properties of DNA. AB - The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy. In contrast to the common assumption of low polarizable behavior like proteins (epsilonr ~ 2-4), we found that the DNA dielectric constant is ~ 8, considerably higher than the value of ~ 3 found for capsid proteins. State-of-the-art molecular dynamic simulations confirm the experimental findings, which result in sensibly decreased DNA interaction free energy than normally predicted by Poisson-Boltzmann methods. Our findings reveal a property at the basis of DNA structure and functions that is needed for realistic theoretical descriptions, and illustrate the synergetic power of scanning probe microscopy and theoretical computation techniques. PMID- 25136105 TI - Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010. AB - In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL -> 221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15-29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic analysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary. PMID- 25136107 TI - Illegal killing for ivory drives global decline in African elephants. AB - Illegal wildlife trade has reached alarming levels globally, extirpating populations of commercially valuable species. As a driver of biodiversity loss, quantifying illegal harvest is essential for conservation and sociopolitical affairs but notoriously difficult. Here we combine field-based carcass monitoring with fine-scale demographic data from an intensively studied wild African elephant population in Samburu, Kenya, to partition mortality into natural and illegal causes. We then expand our analytical framework to model illegal killing rates and population trends of elephants at regional and continental scales using carcass data collected by a Convention on International Trade in Endangered Species program. At the intensively monitored site, illegal killing increased markedly after 2008 and was correlated strongly with the local black market ivory price and increased seizures of ivory destined for China. More broadly, results from application to continental data indicated illegal killing levels were unsustainable for the species between 2010 and 2012, peaking to ~ 8% in 2011 which extrapolates to ~ 40,000 elephants illegally killed and a probable species reduction of ~ 3% that year. Preliminary data from 2013 indicate overharvesting continued. In contrast to the rest of Africa, our analysis corroborates that Central African forest elephants experienced decline throughout the last decade. These results provide the most comprehensive assessment of illegal ivory harvest to date and confirm that current ivory consumption is not sustainable. Further, our approach provides a powerful basis to determine cryptic mortality and gain understanding of the demography of at-risk species. PMID- 25136108 TI - Trachyandesitic volcanism in the early Solar System. AB - Volcanism is a substantial process during crustal growth on planetary bodies and well documented to have occurred in the early Solar System from the recognition of numerous basaltic meteorites. Considering the ureilite parent body (UPB), the compositions of magmas that formed a potential UPB crust and were complementary to the ultramafic ureilite mantle rocks are poorly constrained. Among the Almahata Sitta meteorites, a unique trachyandesite lava (with an oxygen isotope composition identical to that of common ureilites) documents the presence of volatile- and SiO2-rich magmas on the UPB. The magma was extracted at low degrees of disequilibrium partial melting of the UPB mantle. This trachyandesite extends the range of known ancient volcanic, crust-forming rocks and documents that volcanic rocks, similar in composition to trachyandesites on Earth, also formed on small planetary bodies ~ 4.56 billion years ago. It also extends the volcanic activity on the UPB by ~ 1 million years (Ma) and thus constrains the time of disruption of the body to later than 6.5 Ma after the formation of Ca-Al-rich inclusions. PMID- 25136109 TI - Optogenetic neuronal stimulation promotes functional recovery after stroke. AB - Clinical and research efforts have focused on promoting functional recovery after stroke. Brain stimulation strategies are particularly promising because they allow direct manipulation of the target area's excitability. However, elucidating the cell type and mechanisms mediating recovery has been difficult because existing stimulation techniques nonspecifically target all cell types near the stimulated site. To circumvent these barriers, we used optogenetics to selectively activate neurons that express channelrhodopsin 2 and demonstrated that selective neuronal stimulations in the ipsilesional primary motor cortex (iM1) can promote functional recovery. Stroke mice that received repeated neuronal stimulations exhibited significant improvement in cerebral blood flow and the neurovascular coupling response, as well as increased expression of activity-dependent neurotrophins in the contralesional cortex, including brain derived neurotrophic factor, nerve growth factor, and neurotrophin 3. Western analysis also indicated that stimulated mice exhibited a significant increase in the expression of a plasticity marker growth-associated protein 43. Moreover, iM1 neuronal stimulations promoted functional recovery, as stimulated stroke mice showed faster weight gain and performed significantly better in sensory-motor behavior tests. Interestingly, stimulations in normal nonstroke mice did not alter motor behavior or neurotrophin expression, suggesting that the prorecovery effect of selective neuronal stimulations is dependent on the poststroke environment. These results demonstrate that stimulation of neurons in the stroke hemisphere is sufficient to promote recovery. PMID- 25136111 TI - Does aquaculture add resilience to the global food system? AB - Aquaculture is the fastest growing food sector and continues to expand alongside terrestrial crop and livestock production. Using portfolio theory as a conceptual framework, we explore how current interconnections between the aquaculture, crop, livestock, and fisheries sectors act as an impediment to, or an opportunity for, enhanced resilience in the global food system given increased resource scarcity and climate change. Aquaculture can potentially enhance resilience through improved resource use efficiencies and increased diversification of farmed species, locales of production, and feeding strategies. However, aquaculture's reliance on terrestrial crops and wild fish for feeds, its dependence on freshwater and land for culture sites, and its broad array of environmental impacts diminishes its ability to add resilience. Feeds for livestock and farmed fish that are fed rely largely on the same crops, although the fraction destined for aquaculture is presently small (~4%). As demand for high-value fed aquaculture products grows, competition for these crops will also rise, as will the demand for wild fish as feed inputs. Many of these crops and forage fish are also consumed directly by humans and provide essential nutrition for low-income households. Their rising use in aquafeeds has the potential to increase price levels and volatility, worsening food insecurity among the most vulnerable populations. Although the diversification of global food production systems that includes aquaculture offers promise for enhanced resilience, such promise will not be realized if government policies fail to provide adequate incentives for resource efficiency, equity, and environmental protection. PMID- 25136110 TI - Formation and structures of GroEL:GroES2 chaperonin footballs, the protein folding functional form. AB - The GroE chaperonins assist substrate protein (SP) folding by cycling through several conformational states. With each cycle the SP is, in turn, captured, unfolded, briefly encapsulated (t1/2 ~ 1 s), and released by the chaperonin complex. The protein-folding functional form is the US-football-shaped GroEL:GroES2 complex. We report structures of two such "football" complexes to ~ 3.7-A resolution; one is empty whereas the other contains encapsulated SP in both chambers. Although encapsulated SP is not visible on the electron density map, using calibrated FRET and order-of-addition experiments we show that owing to SP catalyzed ADP/ATP exchange both chambers of the football complex encapsulate SP efficiently only if the binding of SP precedes that of ATP. The two rings of GroEL thus behave as a parallel processing machine, rather than functioning alternately. Compared with the bullet-shaped GroEL:GroES1 complex, the GroEL:GroES2 football complex differs conformationally at the GroEL-GroES interface and also at the interface between the two GroEL rings. We propose that the electrostatic interactions between the epsilon-NH(3+) of K105 of helix D in one ring with the negatively charged carboxyl oxygen of A109 at the carboxyl end of helix D of the other ring provide the structural basis for negative inter-ring cooperativity. PMID- 25136112 TI - Automodification switches PARP-1 function from chromatin architectural protein to histone chaperone. AB - Poly [ADP-ribose] polymerase 1 (PARP-1) is a highly abundant chromatin-associated enzyme. It catalyzes the NAD(+)-dependent polymerization of long chains of poly ADP ribose (PAR) onto itself in response to DNA damage and other cues. More recently, the enzymatic activity of PARP-1 has also been implicated in the regulation of gene expression. The molecular basis for the functional switch from chromatin architectural protein to transcription factor and DNA damage responder, triggered by PARP-1 automodification, is unknown. Here, we show that unmodified PARP-1 engages in at least two high-affinity binding modes with chromatin, one of which does not involve free DNA ends, consistent with its role as a chromatin architectural protein. Automodification reduces PARP-1 affinity for intact chromatin but not for nucleosomes with exposed DNA ends. Automodified (AM) PARP-1 has the ability to sequester histones (both in vitro and in cells) and to assemble nucleosomes efficiently in vitro. This unanticipated nucleosome assembly activity of AM-PARP-1, coupled with the fast turnover of the modification, suggests a model in which DNA damage or transcription events trigger transient histone chaperone activity. PMID- 25136113 TI - IL-6/STAT3 promotes regeneration of airway ciliated cells from basal stem cells. AB - The pseudostratified airway epithelium of the lung contains a balanced proportion of multiciliated and secretory luminal cells that are maintained and regenerated by a population of basal stem cells. However, little is known about how these processes are modulated in vivo, and about the potential role of cytokine signaling between stem and progenitor cells and their niche. Using a clonal 3D organoid assay, we found that IL-6 stimulated, and Stat3 inhibitors reduced, the generation of ciliated vs. secretory cells from basal cells. Gain-of-function and loss-of-function studies with cultured mouse and human basal cells suggest that IL-6/Stat3 signaling promotes ciliogenesis at multiple levels, including increases in multicilin gene and forkhead box protein J1 expression and inhibition of the Notch pathway. To test the role of IL-6 in vivo genetically, we followed the regeneration of mouse tracheal epithelium after ablation of luminal cells by inhaled SO2. Stat3 is activated in basal cells and their daughters early in the repair process, correlating with an increase in Il-6 expression in platelet-derived growth factor receptor alpha(+) mesenchymal cells in the stroma. Conditional deletion in basal cells of suppressor of cytokine signaling 3, encoding a negative regulator of the Stat3 pathway, results in an increase in multiciliated cells at the expense of secretory and basal cells. By contrast, Il 6 null mice regenerate fewer ciliated cells and an increased number of secretory cells after injury. The results support a model in which IL-6, produced in the reparative niche, functions to enhance the differentiation of basal cells, and thereby acts as a "friend" to promote airway repair rather than a "foe." PMID- 25136114 TI - Molecular mechanism of pH-dependent substrate transport by an arginine-agmatine antiporter. AB - Enteropathogenic bacteria, exemplified by Escherichia coli, rely on acid resistance systems (ARs) to survive the acidic environment of the stomach. AR3 consumes intracellular protons through decarboxylation of arginine (Arg) in the cytoplasm and exchange of the reaction product agmatine (Agm) with extracellular Arg. The latter process is mediated by the Arg:Agm antiporter AdiC, which is activated in response to acidic pH and remains fully active at pH 6.0 and below. Despite our knowledge of structural information, the molecular mechanism by which AdiC senses acidic pH remains completely unknown. Relying on alanine-scanning mutagenesis and an in vitro proteoliposome-based transport assay, we have identified Tyr74 as a critical pH sensor in AdiC. The AdiC variant Y74A exhibited robust transport activity at all pH values examined while maintaining stringent substrate specificity for Arg:Agm. Replacement of Tyr74 by Phe, but not by any other amino acid, led to the maintenance of pH-dependent substrate transport. These observations, in conjunction with structural information, identify a working model for pH-induced activation of AdiC in which a closed conformation is disrupted by cation-pi interactions between proton and the aromatic side chain of Tyr74. PMID- 25136116 TI - Crystal structure of a nematode-infecting virus. AB - Orsay, the first virus discovered to naturally infect Caenorhabditis elegans or any nematode, has a bipartite, positive-sense RNA genome. Sequence analyses show that Orsay is related to nodaviruses, but molecular characterizations of Orsay reveal several unique features, such as the expression of a capsid-delta fusion protein and the use of an ATG-independent mechanism for translation initiation. Here we report the crystal structure of an Orsay virus-like particle assembled from recombinant capsid protein (CP). Orsay capsid has a T = 3 icosahedral symmetry with 60 trimeric surface spikes. Each CP can be divided into three regions: an N-terminal arm that forms an extended protein interaction network at the capsid interior, an S domain with a jelly-roll, beta-barrel fold forming the continuous capsid, and a P domain that forms surface spike projections. The structure of the Orsay S domain is best aligned to T = 3 plant RNA viruses but exhibits substantial differences compared with the insect-infecting alphanodaviruses, which also lack the P domain in their CPs. The Orsay P domain is remotely related to the P1 domain in calicivirus and hepatitis E virus, suggesting a possible evolutionary relationship. Removing the N-terminal arm produced a slightly expanded capsid with fewer nucleic acids packaged, suggesting that the arm is important for capsid stability and genome packaging. Because C. elegans-Orsay serves as a highly tractable model for studying viral pathogenesis, our results should provide a valuable structural framework for further studies of Orsay replication and infection. PMID- 25136115 TI - Mutation of Plekha7 attenuates salt-sensitive hypertension in the rat. AB - PLEKHA7 (pleckstrin homology domain containing family A member 7) has been found in multiple studies as a candidate gene for human hypertension, yet functional data supporting this association are lacking. We investigated the contribution of this gene to the pathogenesis of salt-sensitive hypertension by mutating Plekha7 in the Dahl salt-sensitive (SS/JrHsdMcwi) rat using zinc-finger nuclease technology. After four weeks on an 8% NaCl diet, homozygous mutant rats had lower mean arterial (149 +/- 9 mmHg vs. 178 +/- 7 mmHg; P < 0.05) and systolic (180 +/- 7 mmHg vs. 213 +/- 8 mmHg; P < 0.05) blood pressure compared with WT littermates. Albumin and protein excretion rates were also significantly lower in mutant rats, demonstrating a renoprotective effect of the mutation. Total peripheral resistance and perivascular fibrosis in the heart and kidney were significantly reduced in Plekha7 mutant animals, suggesting a potential role of the vasculature in the attenuation of hypertension. Indeed, both flow-mediated dilation and endothelium-dependent vasodilation in response to acetylcholine were improved in isolated mesenteric resistance arteries of Plekha7 mutant rats compared with WT. These vascular improvements were correlated with changes in intracellular calcium handling, resulting in increased nitric oxide bioavailability in mutant vessels. Collectively, these data provide the first functional evidence that Plekha7 may contribute to blood pressure regulation and cardiovascular function through its effects on the vasculature. PMID- 25136118 TI - Tomato yellow leaf curl virus resistance by Ty-1 involves increased cytosine methylation of viral genomes and is compromised by cucumber mosaic virus infection. AB - Tomato yellow leaf curl virus (TYLCV) and related begomoviruses are a major threat to tomato production worldwide and, to protect against these viruses, resistance genes from different wild tomato species are introgressed. Recently, the Ty-1 resistance gene was identified, shown to code for an RNA-dependent RNA polymerase and to be allelic with Ty-3. Here we show that upon TYLCV challenging of resistant lines carrying Ty-1 or Ty-3, low virus titers were detected concomitant with the production of relatively high levels of siRNAs whereas, in contrast, susceptible tomato Moneymaker (MM) revealed higher virus titers but lower amounts of siRNAs. Comparative analysis of the spatial genomic siRNA distribution showed a consistent and subtle enrichment for siRNAs derived from the V1 and C3 genes in Ty-1 and Ty-3. In plants containing Ty-2 resistance the virus was hardly detectable, but the siRNA profile resembled the one observed in TYLCV-challenged susceptible tomato (MM). Furthermore, a relative hypermethylation of the TYLCV V1 promoter region was observed in genomic DNA collected from Ty-1 compared with that from (MM). The resistance conferred by Ty 1 was also effective against the bipartite tomato severe rugose begomovirus, where a similar genome hypermethylation of the V1 promoter region was discerned. However, a mixed infection of TYLCV with cucumber mosaic virus compromised the resistance. The results indicate that Ty-1 confers resistance to geminiviruses by increasing cytosine methylation of viral genomes, suggestive of enhanced transcriptional gene silencing. The mechanism of resistance and its durability toward geminiviruses under natural field conditions is discussed. PMID- 25136117 TI - Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells. AB - Epigenetic modifications, such as posttranslational modifications of histones, play an important role in gene expression and regulation. These modifications are in part mediated by the Trithorax group (TrxG) complex and the Polycomb group (PcG) complex, which activate and repress transcription, respectively. We herein investigate the role of Menin, a component of the TrxG complex in T helper (Th) cell differentiation and show a critical role for Menin in differentiation and maintenance of Th17 cells. Menin(-/-) T cells do not efficiently differentiate into Th17 cells, leaving Th1 and Th2 cell differentiation intact in in vitro cultures. Menin deficiency resulted in the attenuation of Th17-induced airway inflammation. In differentiating Th17 cells, Menin directly bound to the Il17a gene locus and was required for the deposition of permissive histone modifications and recruitment of the RNA polymerase II transcriptional complex. Interestingly, although Menin bound to the Rorc locus, Menin was dispensable for the induction of Rorc expression and permissive histone modifications in differentiating Th17 cells. In contrast, Menin was required to maintain expression of Rorc in differentiated Th17 cells, indicating that Menin is essential to stabilize expression of the Rorc gene. Thus, Menin orchestrates Th17 cell differentiation and function by regulating both the induction and maintenance of target gene expression. PMID- 25136119 TI - Electrostatics-driven shape transitions in soft shells. AB - Manipulating the shape of nanoscale objects in a controllable fashion is at the heart of designing materials that act as building blocks for self-assembly or serve as targeted drug delivery carriers. Inducing shape deformations by controlling external parameters is also an important way of designing biomimetic membranes. In this paper, we demonstrate that electrostatics can be used as a tool to manipulate the shape of soft, closed membranes by tuning environmental conditions such as the electrolyte concentration in the medium. Using a molecular dynamics-based simulated annealing procedure, we investigate charged elastic shells that do not exchange material with their environment, such as elastic membranes formed in emulsions or synthetic nanocontainers. We find that by decreasing the salt concentration or increasing the total charge on the shell's surface, the spherical symmetry is broken, leading to the formation of ellipsoids, discs, and bowls. Shape changes are accompanied by a significant lowering of the electrostatic energy and a rise in the surface area of the shell. To substantiate our simulation findings, we show analytically that a uniformly charged disc has a lower Coulomb energy than a sphere of the same volume. Further, we test the robustness of our results by including the effects of charge renormalization in the analysis of the shape transitions and find the latter to be feasible for a wide range of shell volume fractions. PMID- 25136120 TI - Activated group 3 innate lymphoid cells promote T-cell-mediated immune responses. AB - Group 3 innate lymphoid cells (ILC3s) have emerged as important cellular players in tissue repair and innate immunity. Whether these cells meaningfully regulate adaptive immune responses upon activation has yet to be explored. Here we show that upon IL-1beta stimulation, peripheral ILC3s become activated, secrete cytokines, up-regulate surface MHC class II molecules, and express costimulatory molecules. ILC3s can take up latex beads, process protein antigen, and consequently prime CD4(+) T-cell responses in vitro. The cognate interaction of ILC3s and CD4(+) T cells leads to T-cell proliferation both in vitro and in vivo, whereas its disruption impairs specific T-cell and T-dependent B-cell responses in vivo. In addition, the ILC3-CD4(+) T-cell interaction is bidirectional and leads to the activation of ILC3s. Taken together, our data reveal a novel activation-dependent function of peripheral ILC3s in eliciting cognate CD4(+) T cell immune responses. PMID- 25136121 TI - Immune evasion mediated by tumor-derived lactate dehydrogenase induction of NKG2D ligands on myeloid cells in glioblastoma patients. AB - Myeloid cells are key regulators of the tumor microenvironment, governing local immune responses. Here we report that tumor-infiltrating myeloid cells and circulating monocytes in patients with glioblastoma multiforme (GBM) express ligands for activating the Natural killer group 2, member D (NKG2D) receptor, which cause down-regulation of NKG2D on natural killer (NK) cells. Tumor infiltrating NK cells isolated from GBM patients fail to lyse NKG2D ligand expressing tumor cells. We demonstrate that lactate dehydrogenase (LDH) isoform 5 secreted by glioblastoma cells induces NKG2D ligands on monocytes isolated from healthy individuals. Furthermore, sera from GBM patients contain elevated amounts of LDH, which correlate with expression of NKG2D ligands on their autologous circulating monocytes. NKG2D ligands also are present on circulating monocytes isolated from patients with breast, prostate, and hepatitis C virus-induced hepatocellular carcinomas. Together, these findings reveal a previously unidentified immune evasion strategy whereby tumors produce soluble factors that induce NKG2D ligands on myeloid cells, subverting antitumor immune responses. PMID- 25136122 TI - Stimulation of growth by proteorhodopsin phototrophy involves regulation of central metabolic pathways in marine planktonic bacteria. AB - Proteorhodopsin (PR) is present in half of surface ocean bacterioplankton, where its light-driven proton pumping provides energy to cells. Indeed, PR promotes growth or survival in different bacteria. However, the metabolic pathways mediating the light responses remain unknown. We analyzed growth of the PR containing Dokdonia sp. MED134 (where light-stimulated growth had been found) in seawater with low concentrations of mixed [yeast extract and peptone (YEP)] or single (alanine, Ala) carbon compounds as models for rich and poor environments. We discovered changes in gene expression revealing a tightly regulated shift in central metabolic pathways between light and dark conditions. Bacteria showed relatively stronger light responses in Ala compared with YEP. Notably, carbon acquisition pathways shifted toward anaplerotic CO2 fixation in the light, contributing 31 +/- 8% and 24 +/- 6% of the carbon incorporated into biomass in Ala and YEP, respectively. Thus, MED134 was a facultative double mixotroph, i.e., photo- and chemotrophic for its energy source and using both bicarbonate and organic matter as carbon sources. Unexpectedly, relative expression of the glyoxylate shunt genes (isocitrate lyase and malate synthase) was >300-fold higher in the light--but only in Ala--contributing a more efficient use of carbon from organic compounds. We explored these findings in metagenomes and metatranscriptomes and observed similar prevalence of the glyoxylate shunt compared with PR genes and highest expression of the isocitrate lyase gene coinciding with highest solar irradiance. Thus, regulatory interactions between dissolved organic carbon quality and central metabolic pathways critically determine the fitness of surface ocean bacteria engaging in PR phototrophy. PMID- 25136123 TI - Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B protein in human fibroblasts without nuclear DNA damage. AB - Cockayne syndrome (CS) is a human DNA repair-deficient disease that involves transcription coupled repair (TCR), in which three gene products, Cockayne syndrome A (CSA), Cockayne syndrome B (CSB), and ultraviolet stimulated scaffold protein A (UVSSA) cooperate in relieving RNA polymerase II arrest at damaged sites to permit repair of the template strand. Mutation of any of these three genes results in cells with increased sensitivity to UV light and defective TCR. Mutations in CSA or CSB are associated with severe neurological disease but mutations in UVSSA are for the most part only associated with increased photosensitivity. This difference raises questions about the relevance of TCR to neurological disease in CS. We find that CSB-mutated cells, but not UVSSA deficient cells, have increased levels of intramitochondrial reactive oxygen species (ROS), especially when mitochondrial complex I is inhibited by rotenone. Increased ROS would result in oxidative damage to mitochondrial proteins, lipids, and DNA. CSB appears to behave as an electron scavenger in the mitochondria whose absence leads to increased oxidative stress. Mitochondrial ROS, however, did not cause detectable nuclear DNA damage even when base excision repair was blocked by an inhibitor of polyADP ribose polymerase. Neurodegeneration in Cockayne syndrome may therefore be associated with ROS-induced damage in the mitochondria, independent of nuclear TCR. An implication of our present results is that mitochondrial dysfunction involving ROS has a major impact on CS-B pathology, whereas nuclear TCR may have a minimal role. PMID- 25136124 TI - Xylan utilization in human gut commensal bacteria is orchestrated by unique modular organization of polysaccharide-degrading enzymes. AB - Enzymes that degrade dietary and host-derived glycans represent the most abundant functional activities encoded by genes unique to the human gut microbiome. However, the biochemical activities of a vast majority of the glycan-degrading enzymes are poorly understood. Here, we use transcriptome sequencing to understand the diversity of genes expressed by the human gut bacteria Bacteroides intestinalis and Bacteroides ovatus grown in monoculture with the abundant dietary polysaccharide xylan. The most highly induced carbohydrate active genes encode a unique glycoside hydrolase (GH) family 10 endoxylanase (BiXyn10A or BACINT_04215 and BACOVA_04390) that is highly conserved in the Bacteroidetes xylan utilization system. The BiXyn10A modular architecture consists of a GH10 catalytic module disrupted by a 250 amino acid sequence of unknown function. Biochemical analysis of BiXyn10A demonstrated that such insertion sequences encode a new family of carbohydrate-binding modules (CBMs) that binds to xylose configured oligosaccharide/polysaccharide ligands, the substrate of the BiXyn10A enzymatic activity. The crystal structures of CBM1 from BiXyn10A (1.8 A), a cocomplex of BiXyn10A CBM1 with xylohexaose (1.14 A), and the CBM from its homolog in the Prevotella bryantii B14 Xyn10C (1.68 A) reveal an unanticipated mode for ligand binding. A minimal enzyme mix, composed of the gene products of four of the most highly up-regulated genes during growth on wheat arabinoxylan, depolymerizes the polysaccharide into its component sugars. The combined biochemical and biophysical studies presented here provide a framework for understanding fiber metabolism by an important group within the commensal bacterial population known to influence human health. PMID- 25136125 TI - A wave-mechanical model of incoherent quasielastic scattering in complex systems. AB - Quasielastic incoherent neutron scattering (QENS) is an important tool for the exploration of the dynamics of complex systems such as biomolecules, liquids, and glasses. The dynamics is reflected in the energy spectra of the scattered neutrons. Conventionally these spectra are decomposed into a narrow elastic line and a broad quasielastic band. The band is interpreted as being caused by Doppler broadening due to spatial motion of the target molecules. We propose a quantum mechanical model in which there is no separate elastic line. The quasielastic band is composed of sharp lines with twice the natural line width, shifted from the center by a random walk of the protein in the free-energy landscape of the target molecule. The walk is driven by vibrations and by external fluctuations. We first explore the model with the Mossbauer effect. In the subsequent application to QENS we treat the incoming neutron as a de Broglie wave packet. While the wave packet passes the protons in the protein and the hydration shell it exchanges energy with the protein during the passage time of about 100 ns. The energy exchange broadens the ensemble spectrum. Because the exchange involves the free-energy landscape of the protein, the QENS not only provides insight into the protein dynamics, but it may also illuminate the free-energy landscape of the protein-solvent system. PMID- 25136126 TI - A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer. AB - The sorting nexin 27 (SNX27)-retromer complex is a major regulator of endosome-to plasma membrane recycling of transmembrane cargos that contain a PSD95, Dlg1, zo 1 (PDZ)-binding motif. Here we describe the core interaction in SNX27-retromer assembly and its functional relevance for cargo sorting. Crystal structures and NMR experiments reveal that an exposed beta-hairpin in the SNX27 PDZ domain engages a groove in the arrestin-like structure of the vacuolar protein sorting 26A (VPS26A) retromer subunit. The structure establishes how the SNX27 PDZ domain simultaneously binds PDZ-binding motifs and retromer-associated VPS26. Importantly, VPS26A binding increases the affinity of the SNX27 PDZ domain for PDZ- binding motifs by an order of magnitude, revealing cooperativity in cargo selection. With disruption of SNX27 and retromer function linked to synaptic dysfunction and neurodegenerative disease, our work provides the first step, to our knowledge, in the molecular description of this important sorting complex, and more broadly describes a unique interaction between a PDZ domain and an arrestin-like fold. PMID- 25136127 TI - A sharp T-cell antigen receptor signaling threshold for T-cell proliferation. AB - T-cell antigen receptor (TCR) signaling is essential for activation, proliferation, and effector function of T cells. Modulation of both intensity and duration of TCR signaling can regulate these events. However, it remains unclear how individual T cells integrate such signals over time to make critical cell fate decisions. We have previously developed an engineered mutant allele of the critical T-cell kinase zeta-chain-associated protein kinase 70 kDa (Zap70) that is catalytically inhibited by a small molecule inhibitor, thereby blocking TCR signaling specifically and efficiently. We have also characterized a fluorescent reporter Nur77-eGFP transgenic mouse line in which T cells up-regulate GFP uniquely in response to TCR stimulation. The combination of these technologies unmasked a sharp TCR signaling threshold for commitment to cell division both in vitro and in vivo. Further, we demonstrate that this threshold is independent of both the magnitude of the TCR stimulus and Interleukin 2. Similarly, we identify a temporal threshold of TCR signaling that is required for commitment to proliferation, after which T cells are able to proliferate in a Zap70 kinase independent manner. Taken together, our studies reveal a sharp threshold for the magnitude and duration of TCR signaling required for commitment of T cells to proliferation. These results have important implications for understanding T-cell responses to infection and optimizing strategies for immunomodulatory drug delivery. PMID- 25136128 TI - A lipid zipper triggers bacterial invasion. AB - Glycosphingolipids are important structural constituents of cellular membranes. They are involved in the formation of nanodomains ("lipid rafts"), which serve as important signaling platforms. Invasive bacterial pathogens exploit these signaling domains to trigger actin polymerization for the bending of the plasma membrane and the engulfment of the bacterium--a key process in bacterial uptake. However, it is unknown whether glycosphingolipids directly take part in the membrane invagination process. Here, we demonstrate that a "lipid zipper," which is formed by the interaction between the bacterial surface lectin LecA and its cellular receptor, the glycosphingolipid Gb3, triggers plasma membrane bending during host cell invasion of the bacterium Pseudomonas aeruginosa. In vitro experiments with Gb3-containing giant unilamellar vesicles revealed that LecA/Gb3 mediated lipid zippering was sufficient to achieve complete membrane engulfment of the bacterium. In addition, theoretical modeling elucidated that the adhesion energy of the LecA-Gb3 interaction is adequate to drive the engulfment process. In cellulo experiments demonstrated that inhibition of the LecA/Gb3 lipid zipper by either lecA knockout, Gb3 depletion, or application of soluble sugars that interfere with LecA binding to Gb3 significantly lowered P. aeruginosa uptake by host cells. Of note, membrane engulfment of P. aeruginosa occurred independently of actin polymerization, thus corroborating that lipid zippering alone is sufficient for this crucial first step of bacterial host-cell entry. Our study sheds new light on the impact of glycosphingolipids in the cellular invasion of bacterial pathogens and provides a mechanistic explication of the initial uptake processes. PMID- 25136129 TI - Valuing vaccination. AB - Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery. PMID- 25136130 TI - Vaccines, new opportunities for a new society. AB - Vaccination is the most effective medical intervention ever introduced and, together with clean water and sanitation, it has eliminated a large part of the infectious diseases that once killed millions of people. A recent study concluded that since 1924 in the United States alone, vaccines have prevented 40 million cases of diphtheria, 35 million cases of measles, and a total of 103 million cases of childhood diseases. A report from the World Health Organization states that today vaccines prevent 2.5 million deaths per year: Every minute five lives are saved by vaccines worldwide. Overall, vaccines have done and continue to do an excellent job in eliminating or reducing the impact of childhood diseases. Furthermore, thanks to new technologies, vaccines now have the potential to make an enormous contribution to the health of modern society by preventing and treating not only communicable diseases in all ages, but also noncommunicable diseases such as cancer and neurodegenerative disorders. The achievement of these results requires the development of novel technologies and health economic models able to capture not only the mere cost-benefit of vaccination, but also the value of health per se. PMID- 25136131 TI - Efficient biomass pretreatment using ionic liquids derived from lignin and hemicellulose. AB - Ionic liquids (ILs), solvents composed entirely of paired ions, have been used in a variety of process chemistry and renewable energy applications. Imidazolium based ILs effectively dissolve biomass and represent a remarkable platform for biomass pretreatment. Although efficient, imidazolium cations are expensive and thus limited in their large-scale industrial deployment. To replace imidazolium based ILs with those derived from renewable sources, we synthesized a series of tertiary amine-based ILs from aromatic aldehydes derived from lignin and hemicellulose, the major by-products of lignocellulosic biofuel production. Compositional analysis of switchgrass pretreated with ILs derived from vanillin, p-anisaldehyde, and furfural confirmed their efficacy. Enzymatic hydrolysis of pretreated switchgrass allowed for direct comparison of sugar yields and lignin removal between biomass-derived ILs and 1-ethyl-3-methylimidazolium acetate. Although the rate of cellulose hydrolysis for switchgrass pretreated with biomass derived ILs was slightly slower than that of 1-ethyl-3-methylimidazolium acetate, 90-95% glucose and 70-75% xylose yields were obtained for these samples after 72 h incubation. Molecular modeling was used to compare IL solvent parameters with experimentally obtained compositional analysis data. Effective pretreatment of lignocellulose was further investigated by powder X-ray diffraction and glycome profiling of switchgrass cell walls. These studies showed different cellulose structural changes and differences in hemicellulose epitopes between switchgrass pretreatments with the aforementioned ILs. Our concept of deriving ILs from lignocellulosic biomass shows significant potential for the realization of a "closed-loop" process for future lignocellulosic biorefineries and has far reaching economic impacts for other IL-based process technology currently using ILs synthesized from petroleum sources. PMID- 25136132 TI - (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. AB - SET domain containing (lysine methyltransferase) 7 (SETD7) is implicated in multiple signaling and disease related pathways with a broad diversity of reported substrates. Here, we report the discovery of (R)-PFI-2-a first-in-class, potent (Ki (app) = 0.33 nM), selective, and cell-active inhibitor of the methyltransferase activity of human SETD7-and its 500-fold less active enantiomer, (S)-PFI-2. (R)-PFI-2 exhibits an unusual cofactor-dependent and substrate-competitive inhibitory mechanism by occupying the substrate peptide binding groove of SETD7, including the catalytic lysine-binding channel, and by making direct contact with the donor methyl group of the cofactor, S adenosylmethionine. Chemoproteomics experiments using a biotinylated derivative of (R)-PFI-2 demonstrated dose-dependent competition for binding to endogenous SETD7 in MCF7 cells pretreated with (R)-PFI-2. In murine embryonic fibroblasts, (R)-PFI-2 treatment phenocopied the effects of Setd7 deficiency on Hippo pathway signaling, via modulation of the transcriptional coactivator Yes-associated protein (YAP) and regulation of YAP target genes. In confluent MCF7 cells, (R) PFI-2 rapidly altered YAP localization, suggesting continuous and dynamic regulation of YAP by the methyltransferase activity of SETD7. These data establish (R)-PFI-2 and related compounds as a valuable tool-kit for the study of the diverse roles of SETD7 in cells and further validate protein methyltransferases as a druggable target class. PMID- 25136133 TI - Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants. AB - Innate immunity confers an immediate nonspecific mechanism of microbial recognition through germ line-encoded pattern recognition receptors (PRRs). Of these, Toll-like receptors (TLRs) and nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) have shaped our current understanding of innate regulation of adaptive immunity. It is now recognized that PRRs are paramount in instructing an appropriate adaptive immune response. Their ligands have been the focus of adjuvant research with the goal of generating modern vaccine combinations tailored to specific pathogens. In this review we will highlight the recent findings in the field of adjuvant research with a particular focus on the potential of TLR and NLR ligands as adjuvants and their influence on adaptive immune responses. PMID- 25136134 TI - History of vaccination. AB - Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before. PMID- 25136136 TI - Local anesthetic and antiepileptic drug access and binding to a bacterial voltage gated sodium channel. AB - Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the "hinged lid"-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water-protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors. PMID- 25136135 TI - Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease. AB - Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease. PMID- 25136138 TI - Demographic characteristics of doctors who intend to follow clinical academic careers: UK national questionnaire surveys. AB - OBJECTIVES: It is well recognised that women are underrepresented in clinical academic posts. Our aim was to determine which of a number of characteristics notably gender, but also ethnicity, possession of an intercalated degree, medical school attended, choice of specialty-were predictive of doctors' intentions to follow clinical academic careers. DESIGN: Questionnaires to all UK-trained medical graduates of 2005 sent in 2006 and again in 2010, graduates of 2009 in 2010 and graduates of 2012 in 2013. RESULTS: At the end of their first year of medical work, 13.5% (368/2732) of men and 7.3% (358/4891) of women specified that they intended to apply for a clinical academic training post; and 6.0% (172/2873) of men and 2.2% (111/5044) of women specified that they intended to pursue clinical academic medicine as their eventual career. A higher percentage of Asian (4.8%) than White doctors (3.3%) wanted a long-term career as a clinical academic, as did a higher percentage of doctors who did an intercalated degree (5.6%) than others (2.2%) and a higher percentage of Oxbridge graduates (8.1%) than others (2.8%). Of the graduates of 2005, only 30% of those who in 2006 intended a clinical medicine career also did so when re-surveyed in 2010 (men 44%, women 12%). CONCLUSIONS: There are noteworthy differences by gender and other demographic factors in doctors' intentions to pursue academic training and careers. The gap between men and women in aspirations for a clinical academic career is present as early as the first year after qualification. PMID- 25136137 TI - Endothelial Akt1 mediates angiogenesis by phosphorylating multiple angiogenic substrates. AB - The PI3K/Akt pathway is necessary for several key endothelial cell (EC) functions, including cell growth, migration, survival, and vascular tone. However, existing literature supports the idea that Akt can be either pro- or antiangiogenic, possibly due to compensation by multiple isoforms in the EC when a single isoform is deleted. Thus, biochemical, genetic, and proteomic studies were conducted to examine isoform-substrate specificity for Akt1 vs. Akt2. In vitro, Akt1 preferentially phosphorylates endothelial nitric oxide synthase (eNOS) and promotes NO release, whereas nonphysiological overexpression of Akt2 can bypass the loss of Akt1. Conditional deletion of Akt1 in the EC, in the absence or presence of Akt2, retards retinal angiogenesis, implying that Akt1 exerts a nonredundant function during physiological angiogenesis. Finally, proteomic analysis of Akt substrates isolated from Akt1- or Akt2-deficient ECs documents that phosphorylation of multiple Akt substrates regulating angiogenic signaling is reduced in Akt1-deficient, but not Akt2-deficient, ECs, including eNOS and Forkhead box proteins. Therefore, Akt1 promotes angiogenesis largely due to phosphorylation and regulation of important downstream effectors that promote aspects of angiogenic signaling. PMID- 25136139 TI - Patients as teachers: a randomised controlled trial on the use of personal stories of harm to raise awareness of patient safety for doctors in training. AB - BACKGROUND: Patient safety training often provides learners with a health professional's perspective rather than the patient's. Personal narratives of health-related harm allow patients to share their stories with health professionals to influence clinical behaviour by rousing emotions and improving attitudes to safety. AIM: This study measured the impact of patient narratives used to train junior doctors in patient safety. METHODS: An open, multi-centre, two-arm, parallel design randomised controlled trial was conducted in the North Yorkshire East Coast Foundation School (NYECFS). The intervention consisted of 1 h-long patient narratives followed by discussion. The control arm received conventional faculty-delivered teaching. The Attitude to Patient Safety Questionnaire (APSQ) and the Positive and Negative Affect Schedule (PANAS) were used to measure the impact of the intervention. RESULTS: 142 trainees received the intervention; 141 the control teaching. There was no evidence of a difference in post-intervention APSQ scores between the groups. There was a statistically significant difference in the underlying distribution of both post PA (positive affect) and post NA (negative affect) scores between the groups on the PANAS (p<0.001) with indications of both higher PA and NA scores in the intervention group. CONCLUSIONS: Involving patients with experiences of safety incidents in training has an ideological appeal and seems an obvious choice in designing safety interventions. On the basis of our primary outcome measure, we were unable to demonstrate effectiveness of the intervention in changing general attitudes to safety compared to control. While the intervention may impact on emotional engagement and learning about communication, we remain uncertain whether this will translate into improved behaviours in the clinical context or indeed if there are any negative effects. TRIAL REGISTRATION NUMBER: Grant reference no. RP PG-0108-10049. PMID- 25136140 TI - Evaluation of hospital factors associated with hospital postoperative venous thromboembolism imaging utilisation practices. AB - BACKGROUND: Recent research suggests that hospital rates of postoperative venous thromboembolism (VTE) are subject to surveillance bias: the more hospitals 'look for' VTE, the more VTE they find. However, little is known about what drives variation in hospital VTE imaging rates. We conducted an observational study to examine hospital and market characteristics that were associated with hospital level rates of postoperative VTE imaging, focusing on hospitals with particularly high rates. METHODS: For Medicare beneficiaries undergoing 11 major operations (2009-2010) at 2820 hospitals, hospital-level postoperative VTE imaging use rates were calculated. Hospital characteristics associated with hospital VTE imaging use rates were examined including case severity, size, ownership, VTE process measure adherence, accreditations, staffing, malpractice environment, and county market factors. Associations between explanatory variables and VTE imaging rates were assessed using quantile regressions at the 25th, median, 75th and 90th quantiles. RESULTS: Mean postoperative VTE imaging rates ranged from 85.26 (SD=67.38) per 1000 discharges in the lowest quartile of hospitals ranked by VTE imaging rates to 168.86 (SD=76.70) in the highest quartile. Drivers of high imaging rates at the 90th quantile were high resident-to-bed ratio (coefficient=51.35, p<0.01), Joint Commission accreditation (coefficient=19.05, p<0.01), presence of other hospitals in the same market with high imaging rates (coefficient=15.29, p<0.01), average case severity (coefficient=11.97, p<0.01), local malpractice costs (coefficient=11.29, p<0.01), and market competition (coefficient=11.03, p<0.01). CONCLUSIONS: Hospital teaching status, resident-to bed ratio, malpractice environment and local market factors drive hospital postoperative VTE imaging use, suggesting that non-clinical forces predominantly drive hospital VTE imaging practices. PMID- 25136142 TI - Family Economic Strengthening and Parenting Stress Among Caregivers of AIDS Orphaned Children: Results from a Cluster Randomized Clinical Trial in Uganda. AB - This study examines the impact of a family economic strengthening intervention on parenting stress among caregivers of AIDS-orphaned children in Uganda. The study uses data from a 4-year (2008-2012) NIMH randomized clinical trial for AIDS orphaned children known as Suubi-Maka (N=346 dyads). Child-caregiver dyads from 10 comparable primary schools were randomly assigned to either the control group (n=167 dyads) receiving usual care for school-going orphaned children (such as food aid and scholastic materials) or the treatment group (n=179 dyads) receiving a family economic strengthening intervention (focused on a matched savings account), financial planning and management workshops over and above the usual care. Interviews were conducted at baseline, 12 months and 24 months follow-up. This study uses data from baseline and 24 months post-intervention. We use multivariate regression methods, controlling for socioeconomic characteristics. At 24 months, caregivers in the treatment group reported significantly lower levels of parenting stress compared to caregivers in the control group. Findings from this study point to the potential of a family economic strengthening intervention to improve caregiver's psychosocial wellbeing and that of their families. We conclude that programs and policies aimed at improving the psychosocial wellbeing of families caring for AIDS-orphaned children may consider incorporating economic strengthening components in their programming to help support these kinds of families, caregivers of AIDS-orphaned children especially those residing in developing countries. PMID- 25136141 TI - Learning from mistakes in clinical practice guidelines: the case of perioperative beta-blockade. PMID- 25136143 TI - The effect of a community-based, primary health care exercise program on inflammatory biomarkers and hormone levels. AB - The aim of this study was to analyze the impact of a community-based exercise program in primary care on inflammatory biomarkers and hormone levels. The 1-year quasiexperimental study involved 13 women (mean age = 56.8 +/- 11.4 years) and it was developed in two basic health care units in Rio Claro City, Brazil. The physical exercise intervention was comprised of two, 60-minute sessions/week. The inflammatory biomarkers were measured at baseline, 6 months, and 1 year. Repeated measures ANOVA analyses indicated that the intervention was effective in reducing CRP and TNFalpha after 1 year compared to baseline and 6 months (P < 0.05). There were no changes in IL10, IL6, and insulin after 1 year. However, leptin significantly increased at 1 year (P = 0.016). The major finding of this study is that a community-based exercise program can result in a decrease or maintenance of inflammatory biomarkers after 1 year, and thus has the potential to be a viable public health approach for chronic disease prevention. PMID- 25136145 TI - The Wnt/beta-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria. AB - Innate immunity against pathogenic bacteria is critical to protect host cells from invasion and infection as well as to develop an appropriate adaptive immune response. During bacterial infection, different signaling transduction pathways control the expression of a wide range of genes that orchestrate a number of molecular and cellular events to eliminate the invading microorganisms and regulate inflammation. The inflammatory response must be tightly regulated because uncontrolled inflammation may lead to tissue injury. Among the many signaling pathways activated, the canonical Wnt/beta-catenin has been recently shown to play an important role in the expression of several inflammatory molecules during bacterial infections. Our main goal in this review is to discuss the mechanism used by several pathogenic bacteria to modulate the inflammatory response through the Wnt/beta-catenin signaling pathway. We think that a deep insight into the role of Wnt/beta-catenin signaling in the inflammation may open new venues for biotechnological approaches designed to control bacterial infectious diseases. PMID- 25136144 TI - Immunologic biomarkers for clinical and therapeutic management of psoriasis. AB - BACKGROUND: The therapeutic management of psoriasis includes conventional treatments as well as the new generation of highly effective TNF-alpha inhibitors. However, psoriasis has proven to be a complex therapeutic challenge and treatment failures are not uncommon. Thus, laboratory biomarkers of disease progression/therapeutic efficacy may greatly help in the clinical management of psoriasis. AIMS: To identify laboratory biomarkers for clinical management and therapeutic monitoring of psoriasis. METHODS: An observational study performed on 59 patients, presenting moderate to severe psoriasis, undergoing treatment with anti-TNF-alpha agents (etanercept, adalimumab, and infliximab). Soluble and cellular immune/inflammatory parameters were assessed at baseline and after 12 and 24 weeks of treatment. RESULTS: Clinical efficacy was achieved in 88% of the subjects at 12 weeks, reaching 90% after 24 weeks. IL-6 and IL-22, which were elevated at baseline, were significantly reduced, in association with a significant decrease of CLA+ T cells and an increase of Treg lymphocytes. T, B, and NK cell subsets and T cell response to recall antigens did not show any evidence of immune suppression. CONCLUSIONS: Immune/inflammatory parameters including IL-6 and IL-22, CLA+ T cells, and Treg lymphocytes may prove to be valuable laboratory tools for the clinical and therapeutic monitoring of psoriasis. PMID- 25136146 TI - IL-17 genetic and immunophenotypic evaluation in chronic graft-versus-host disease. AB - Although interleukin-17 (IL-17) is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus host disease (cGVHD) was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4(+) T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL 17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD. PMID- 25136147 TI - Intraperitoneal infusion of mesenchymal stem/stromal cells prevents experimental autoimmune uveitis in mice. AB - Autoimmune uveitis is one of the leading causes of blindness. We here investigated whether intraperitoneal administration of human mesenchymal stem/stromal cells (hMSCs) might prevent development of experimental autoimmune uveitis (EAU) in mice. Time course study showed that the number of IFN-gamma- or IL-17-expressing CD4(+) T cells was increased in draining lymph nodes (DLNs) on the postimmunization day 7 and decreased thereafter. The retinal structure was severely disrupted on day 21. An intraperitoneal injection of hMSCs at the time of immunization protected the retina from damage and suppressed the levels of proinflammatory cytokines in the eye. Analysis of DLNs on day 7 showed that hMSCs decreased the number of Th1 and Th17 cells. The hMSCs did not reduce the levels of IL-1beta, IL-6, IL-12, and IL-23 which are the cytokines that drive Th1/Th17 differentiation. Also, hMSCs did not induce CD4(+)CD25(+)Foxp3(+) cells. However, hMSCs increased the level of an immunoregulatory cytokine IL-10 and the population of IL-10-expressing B220(+)CD19(+) cells. Together, data demonstrate that hMSCs attenuate EAU by suppressing Th1/Th17 cells and induce IL-10 expressing B220(+)CD19(+) cells. Our results support suggestions that hMSCs may offer a therapy for autoimmune diseases mediated by Th1/Th17 responses. PMID- 25136150 TI - Healthcare as an electoral agenda. PMID- 25136151 TI - Achieving universal health coverage through community empowerment: a proposition for bangladesh. PMID- 25136148 TI - Switching off key signaling survival molecules to switch on the resolution of inflammation. AB - Inflammation is a physiological response of the immune system to injury or infection but may become chronic. In general, inflammation is self-limiting and resolves by activating a termination program named resolution of inflammation. It has been argued that unresolved inflammation may be the basis of a variety of chronic inflammatory diseases. Resolution of inflammation is an active process that is fine-tuned by the production of proresolving mediators and the shutdown of intracellular signaling molecules associated with cytokine production and leukocyte survival. Apoptosis of leukocytes (especially granulocytes) is a key element in the resolution of inflammation and several signaling molecules are thought to be involved in this process. Here, we explore key signaling molecules and some mediators that are crucial regulators of leukocyte survival in vivo and that may be targeted for therapeutic purposes in the context of chronic inflammatory diseases. PMID- 25136149 TI - Antagonizing arachidonic acid-derived eicosanoids reduces inflammatory Th17 and Th1 cell-mediated inflammation and colitis severity. AB - During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA-) derived eicosanoids, such as prostaglandin E2 (PGE2), promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS-) induced colitis. Fat-1 mice contain the omega3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Delta5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORgammatau, and IL-23), decreased percentages of Th17 cells and, improved colon injury scores (P <= 0.05). Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation. PMID- 25136153 TI - Managing self for leadership. PMID- 25136152 TI - Maternal near miss: an indicator for maternal health and maternal care. AB - Maternal mortality is one of the important indicators used for the measurement of maternal health. Although maternal mortality ratio remains high, maternal deaths in absolute numbers are rare in a community. To overcome this challenge, maternal near miss has been suggested as a compliment to maternal death. It is defined as pregnant or recently delivered woman who survived a complication during pregnancy, childbirth or 42 days after termination of pregnancy. So far various nomenclature and criteria have been used to identify maternal near-miss cases and there is lack of uniform criteria for identification of near miss. The World Health Organization recently published criteria based on markers of management and organ dysfunction, which would enable systematic data collection on near miss and development of summary estimates. The prevalence of near miss is higher in developing countries and causes are similar to those of maternal mortality namely hemorrhage, hypertensive disorders, sepsis and obstructed labor. Reviewing near miss cases provide significant information about the three delays in health seeking so that appropriate action is taken. It is useful in identifying health system failures and assessment of quality of maternal health-care. Certain maternal near miss indicators have been suggested to evaluate the quality of care. The near miss approach will be an important tool in evaluation and assessment of the newer strategies for improving maternal health. PMID- 25136154 TI - A Clinical Study of Vitiligo in a Rural Set up of Gujarat. AB - INTRODUCTION: Vitiligo is an acquired depigmentary condition caused by inactivation or destruction of melanocytes in epidermis and hair follicle. Worldwide incidence of 1% has been reported; similar to various dermatological clinics in India. Widespread prejudice, ignorance, taboos, lack of scientific appraisal, and confusion of vitiligo with leprosy makes it an immense psychological stress. AIM: To know the clinical profile of vitiligo patient with associated cofactors. MATERIALS AND METHODS: Total 1,010 patients of vitiligo attended in outpatient department at Shree Krishna Hospital (SKH) and Matar camp, Gujarat over 1 year period from August 2011 to July 2012 were included in this study. Detail history and clinical examination of patients were done. RESULTS: Out of 1,010 patients 57.3% were females and 42.7 % were males. Most cases developed vitiligo by 2(nd) decade of life. Progressive course was found in 60.9 % of patients. Vitiligo vulgaris (57.8%) was most common morphological type. Most common site of onset (41.5%) and involvement (75.7%) was lower limb. Family history was present in 20.4%. CONCLUSIONS: Vitiligo constitutes important dermatological disease especially in India. The data suggest that local epidemiological behavior of vitiligo need not be the same across different regions. Vitiligo differs substantially in various clinical aspects. PMID- 25136155 TI - Challenges in Developing Competency-based Training Curriculum for Food Safety Regulators in India. AB - CONTEXT: The Food Safety and Standards Act have redefined the roles and responsibilities of food regulatory workforce and calls for highly skilled human resources as it involves complex management procedures. AIMS: 1) Identify the competencies needed among the food regulatory workforce in India. 2) Develop a competency-based training curriculum for food safety regulators in the country. 3) Develop training materials for use to train the food regulatory workforce. SETTINGS AND DESIGN: The Indian Institute of Public Health, Hyderabad, led the development of training curriculum on food safety with technical assistance from the Royal Society for Public Health, UK and the National Institute of Nutrition, India. The exercise was to facilitate the implementation of new Act by undertaking capacity building through a comprehensive training program. MATERIALS AND METHODS: A competency-based training needs assessment was conducted before undertaking the development of the training materials. RESULTS: THE TRAINING PROGRAM FOR FOOD SAFETY OFFICERS WAS DESIGNED TO COMPRISE OF FIVE MODULES TO INCLUDE: Food science and technology, Food safety management systems, Food safety legislation, Enforcement of food safety regulations, and Administrative functions. Each module has a facilitator guide for the tutor and a handbook for the participant. Essentials of Food Hygiene-I (Basic level), II and III (Retail/ Catering/ Manufacturing) were primarily designed for training of food handlers and are part of essential reading for food safety regulators. CONCLUSION: The Food Safety and Standards Act calls for highly skilled human resources as it involves complex management procedures. Despite having developed a comprehensive competency-based training curriculum by joint efforts by the local, national, and international agencies, implementation remains a challenge in resource-limited setting. PMID- 25136156 TI - Antibiotic susceptibility profile of bacteria isolated from natural sources of water from rural areas of East sikkim. AB - BACKGROUND: Contamination of water, food, and environment with antibiotic resistant bacteria poses a serious public health issue. OBJECTIVE: The objective was to study the bacterial pollution of the natural sources of water in east Sikkim and to determine the antimicrobial profile of the bacterial isolates. MATERIALS AND METHODS: A total of 225 samples, 75 each during winter, summer, and monsoon season were collected from the same source in every season for bacteriological analysis by membrane filtration method. Antibiotic susceptibility test was performed using standard disc diffusion method. RESULTS: A total of 19 bacterial species of the genera Escherichia, Klebsiella, Proteus, Salmonella, Shigella, Enterobacter, Citrobacter, Morganella, Pseudomonas, Acinetobacter, Flavobacterium, and Serratia were isolated and their antimicrobial sensitivity tested. Generally, most bacterial isolates except Salmonella and Shigella species were found resistant to commonly used antibiotics such as ampicillin (57.5%), trimethoprim/sulfamethoxaole (39.1%), amoxicillin/clavulanic acid (37.4%), cefixime (34.5%), tetracycline (29.1%), ceftazidime (26.3%), ofloxacin (25.9%), amikacin (8.7%), and gentamicin (2.7%) but sensitive to imipenem and piperacillin/tazobactam. CONCLUSION: Natural sources of water in east Sikkim are grossly contaminated with bacteria including enteropathogens. The consumption of untreated water from these sources might pose health risk to consumers. PMID- 25136157 TI - Anthropometric and Nutritional Profile of People Living with HIV and AIDS in India: an Assessment. AB - BACKGROUND: Importance of nutrition in human immunodeficiency virus (HIV) is well established; however, the information regarding the diet quality of people living with HIV (PLHIV) especially in India is lacking. OBJECTIVES: The objective of this study is to assess the anthropometric and nutritional profile of Indian PLHIV. MATERIAL AND METHODS: The study was performed on 400 adult PLHIV registered at the Antiretroviral Center (ART) center in New Delhi, India. Anthropometric data including height, weight, waist, hip, mid arm, and calf circumferences, were collected; 1-day 24-h dietary recall was done to gather nutrient intake from which nutrient adequacy ratios were computed. Mini Nutritional Assessment (MNA) was also conducted. RESULTS: The mean body mass index (BMI) of the sample was 19.73 +/- 3.55 kg/m(2) with around 40% having BMI <18.5 kg/m(2) . All anthropometric measurements were found to correlate positively and significantly with CD4 count (P < 0.05). The sample consumed poor quality of diet as they could not meet even the 2/3(rd) of the Indian Council of Medical Research (2010) requirements for energy, protein, calcium, iron, riboflavin, niacin, folic acid, B12, copper, and zinc. Classification of subjects according to MNA indicated that more than 50% of the sample was at-risk of malnutrition and 34% were malnourished. With 40% of sample having BMI less than normal, 50% at risk of malnutrition together with poor nutrient intakes over a long period of time could contribute to further worsening of the nutritional status. CONCLUSION: There is a need to develop a database on nutritional profile of PLHIV in India which reinforces the need for development of effective strategies to improve their nutritional status. PMID- 25136158 TI - Nutritional Status of under 5 Children belonging to Tribal Population Living in Riverine (Char) Areas of Dibrugarh District, Assam. AB - CONTEXT: Assam's main lifeline, the Brahmaputra river, braided nature created numerous sand bars and islands known as chars/sapories. They are home to more than 3 million people. Over 90% of the cultivated land on the river islands is flood-prone; the flood leaves the islands completely separated from mainland, preventing access to health infrastructure and services. AIMS: To assess the nutritional status of under 5 children residing in the char areas of Dibrugarh district and to identify the factors influencing their nutritional status. SETTINGS AND DESIGN: A community-based cross-sectional study conducted in the riverine areas of Dibrugarh district of Assam. MATERIALS AND METHODS: Nutritional status was assessed using anthropometry. Undernutrition was classified using World Health Organization (WHO) recommended Z- score system. Data collection was done by house to house visit of all chars using proportionate allocation. STATISTICAL ANALYSIS USED: Rates, ratios, proportions, and chi-square test. RESULTS: Overall prevalence of underweight, stunting, and wasting was 29%, 30.4%, and 21.6%, respectively. Prevalence of underweight and stunting was less than the prevalence of underweight (36.4%) and stunting (46.5%) in Assam, but the prevalence of wasting was more than that of Assam (13.7%) as observed in National Family Health Survey-3. Significant association was observed between the prevalence of undernutrition and socioeconomic status, literacy status of parents, infant, and young child feeding practices and size of the family (P < 0.05). CONCLUSIONS: Special focus is needed for nutritional improvement of under 5 living in char areas to prevent preventable morbidities and to achieve optimum development. PMID- 25136159 TI - Health issues amongst call center employees, an emerging occupational group in India. AB - Call center sector in India is a relatively new industry and one of the fastest growing sectors driving employment and growth in modern India today. While employment in the business process outsourcing (BPO) sector has meant that young adults are reaching their career milestones and financial goals much earlier than before, surveys and anecdotal evidence show that workers in the BPO sector experience high levels of stress and its related disorders, primarily due to its contemporary work settings. Safeguarding the health of youngsters employed in this new, growing economy becomes an occupational health challenge to public health specialists. PMID- 25136160 TI - Mobile-health approach: a critical look on its capacity to augment health system of developing countries. AB - BACKGROUND: The mobile-health approach is currently knocking the doors of public health to make use of this rapidly advancing technology in developing countries; therefore, it needs a critical look on its capacity in improving health system of developing countries. MATERIALS AND METHODS: A systematic review of studies in literature published till 31(st) October 2013 of last 10 years on key search word: Capacity of mobile-health in improving health system of developing countries was done from medical search engines abstracting databases such as Pub med, WHO, Cochrane database, Google scholar, and Bio-med Central. Both types of studies elucidating utility and no benefit of mobile-health in developing countries were included as main criteria for deciding the capacity of mobile health approach in health system of developing countries. M-health studies on areas of impact, effectiveness, and evaluation and previous reviews, conferences data, and exploratory studies were the main study designs incorporated. Studies on m-health in developed world, Indian studies as well data from thesis or dissertation were excluded in this review. DISCUSSION: Multi-faceted mobile health applications, strategies, and approaches currently lack proper regulation and standardization from health care authorities, and currently their results also vary from good to no beneficial effects as found in this review. CONCLUSION: Umbrella of mobile-health approaches must be used intelligently, keeping in mind the fact that, it can provide a greater access and quality health care to larger segments of a rural population and its potential to improve the capacity of health system in developing countries. PMID- 25136161 TI - Trends of transfusion transmissible diseases among blood donors at uttarakhand, India. AB - CONTEXT: Blood can save lives; however, it can be a source of transfusion transmitted diseases if proper screening of donated blood is not done. It is now mandatory to screen all donated blood units, whether replacement or voluntary for five transfusion transmitted diseases-namely human immunodeficiency virus (HIV), hepatitis B and C, syphilis, and malaria. AIMS: The present study was done to study the prevalence of infectious disease markers among donors at the blood bank of a tertiary care center. SETTINGS AND DESIGN: A total of 53,069 donors donated blood over 11 years. The number of replacement and voluntary donors was 41,710 and 11,359, respectively. MATERIALS AND METHODS: Screening of blood units was done by enzyme-linked immunosorbent assay (ELISA) method for HIV and hepatitis B and C. HIV testing was done using fourth generation ELISA kits. Syphilis was tested by latex agglutination assay and malaria was tested using slide method up to the year 2008-2009 and by rapid immunochromatographic assay after that. RESULTS: The mean percentage of these infections per year was found to be 0.2, 1.2, 0.9, 0.3, and 0.002% for HIV, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), syphilis, and malarial parasite (MP), respectively. CONCLUSIONS: The risk of transfusion transmissible infection (TTI) today is low but supply of safe blood depends on proper donor selection and sensitive screening tests. PMID- 25136163 TI - Tobacco Addiction Among Dental Students: A Reality to be Addressed. PMID- 25136162 TI - Anemia in elderly: the need to combat the problem. PMID- 25136164 TI - Metabolic syndrome in the rural population of wardha, central India: confounding of factor analysis as result of high correlated variables. PMID- 25136165 TI - Thinking beyond the thomson reuters "impact factor". PMID- 25136166 TI - Fertility sparing surgery in gynecologic cancer. AB - Fertility preservation is one of the major concerns of young patients diagnosed with gynecological cancer. With newer treatment regimens and better surgical techniques, survival rates after cancer treatment have improved, hence preservation of fertility has recently become an important issue in the treatment of gynecological cancers. Fertility sparing surgery may be an option for early stage cervical cancer with the development of loop excision techniques and radical trachelectomy which allows a radical approach to cervix cancer at the same time preserving the uterus and thus fertility. Fertility preservation is possible in Stage 1 epithelial ovarian cancers, germ cell ovarian tumors, and borderline cancers. Hormonal therapy with progestin agents is effective in early endometrial cancer. In patients desiring future pregnancy, fertility sparing options must be explored before starting treatment for gynecologic cancers. PMID- 25136167 TI - The never ending debate single-layer versus double-layer closure of the uterine incision at cesarean section. PMID- 25136168 TI - Impact of structured counseling on the selection of hormonal contraceptive methods: results of a multi-centric, observational study in India. AB - OBJECTIVE: To determine the influence of "structured contraception counseling" on Indian women's selection of contraceptive methods. METHODS: Women (>=18 and <=40 years) requesting contraception were enrolled at 36 sites. "Structured contraception counseling" was provided by a health care professional on the available contraceptive methods. Questionnaires on the women's pre- and post counseling contraceptive choice, her perceptions, and the reasons behind her post counseling decision were filled. RESULTS: Significant reductions were observed in the proportion of women who were indecisive (n = 260; 31.5 % pre-counseling vs. n = 30; 3.6 %, post-counseling [P < 0.001]) and women opting for non-hormonal method (24.6 % pre-counseling vs. 6.8 % post-counseling, [P < 0.001]). Of all the women counseled (n = 825), 89.6 % (739/825) of women chose a hormonal contraceptive method. There were significant difference (P < 0.001) in the women's choice of contraceptive in the pre- and post-counseling sessions, respectively (combined oral contraceptive: 30.8 vs. 40.7 %; vaginal ring: 1.8 vs. 14.1 %; progestogen only pills: 1.6 vs. 7.9 %; injectable-depot medroxyprogesterone acetate: 5.9 vs. 13.6 %; levonorgestrel-intrauterine system: 3.8 vs. 13.3 %). CONCLUSIONS: Structured contraception counseling using standardized protocol and aids resulted in a significant increase in the selection of modern contraceptive methods. Post-counseling majority of women opted for hormonal methods with an increase in selection of pills and newer alternatives. PMID- 25136169 TI - Trends in cesarean delivery: rate and indications. AB - OBJECTIVES: To compare the cesarean delivery rates over the last decade and to examine the indications contributing to changed trends, if any. METHODS: To compare the rate and indications of cesarean delivery over the last decade, the data were collected in a retrospective manner from all the deliveries that occurred between January 1 and December 31 in 2001, 2006, and 2011, in the department of obstetrics and gynecology, Seth G.S. Medical College and K.E.M. Hospital, a large tertiary care municipal hospital in Western India. A cohort of 20853 delivered women was studied. The rates and indications of primary and repeat cesarean sections were analyzed among the live births to estimate the relative contribution of each indication to the overall increase in rate. RESULTS: The cesarean delivery rate increased from 171.70 to 289.30 per 1,000 live births, with an increase in primary cesarean delivery rate from 118.53 (69.03 %) in 2001 to 210.09 (72.62 %) in 2011 per 1,000 live births. Fetal distress, arrest of descent, multiple gestations, and fetal indications contributed to this increase. CONCLUSIONS: There is a significant increase in the total cesarean rate with primary cesarean accounting for most of the increase. PMID- 25136170 TI - An analysis of pregnancy outcome in dichorionic and monochorionic twins given special antenatal and intranatal care: a four-year survey. AB - OBJECTIVE: The present study aims to analyze perinatal outcomes in twins given special care during pregnancy and labor and to compare fetal and neonatal outcomes in dichorionic twins with monochorionic twins. STUDY DESIGN: Eighty eight (88) twin pregnancies booked for care at a tertiary care Fetal Medicine centre were included in this study. The maternal demographic variables, course of pregnancy, fetal problems, and specialized fetal therapeutic and diagnostic interventions were noted. The above parameters were compared in the sub-groups of dichorionic and monochorionic twin pregnancies and related to the perinatal outcome. Statistical analysis was done using the student's t test and the two tailed chi sqaure tests with Yate's continuity correction. A p value <0.05 was considered as significant. RESULTS: Mean maternal age was 30.34 + 4.81 years (range 19-48). 81 % of the twins were DCDA, and 19 % were MCDA. The mean gestational age at delivery was 34.4 +/- 3.5 weeks, and this was not significantly different in MCDA and DCDA groups. Serious fetal problems warranting intervention at the time of initial referral were significantly higher in MCDA twins although overall perinatal outcome in both groups were not different. CONCLUSION: Specialized care during pregnancy and labor including active fetal surveillance and therapeutic intervention when indicated improves the perinatal outcome in twin pregnancies and ensured at least one healthy live birth in over 90 % cases, although with an increase in late prematurity. PMID- 25136171 TI - An observational study of various predictors of success of vaginal delivery following a previous cesarean section. AB - OBJECTIVES: To study the various predictors of success for vaginal birth after cesarean (VBAC) and to study the maternal and fetal outcomes in them and their comparison with control group. METHODS: This prospective observational study included 100 women with previous cesarean section in the study group and 100 primigravidas in the control group. Various predictors for success of VBAC were analyzed and maternal and fetal outcomes were compared with the control group using student t test, Pearson chi (2) test, and Mann-Whitney U test. RESULTS: Of 100 women with prior cesarean Sect. 65 had successful trial of labor, while 35 underwent a repeat cesarean section. Maternal complications in the previous CS group were 15 % as compared to only 2 % in the control group (p < 0.001). CONCLUSION: Maternal pre-pregnancy BMI, non-recurring indications of previous cesarean section, good Bishop's score at the time of admission, spontaneous onset of labor, and neonatal birth weight were significantly related to high chances of success of vaginal birth after previous cesarean section. Maternal complications were more common in study group, but the fetal outcomes were similar. PMID- 25136172 TI - The outcome of septic abortion: a tertiary care hospital experience. AB - OBJECTIVE: To study the incidence of septic abortion, reasons for that, sociodemographic profile, abortion providers, complications faced, and treatment given and its outcome. METHODS: All the women with septic abortion admitted at Government Maternity Hospital, Tirupathi, over a period of 2 years 4 months duration from July 2007 to October 2009 were studied prospectively. OBSERVATIONS AND RESULTS: Incidence of septic abortion in our study was 6.78 %. 72 % of cases were performed by qualified medical personnel. Fourteen patients had complications, among them peritonitis, pelvic abscess, renal failure, and septic shock were common. Twenty-six patients had Grade-I sepsis, Grade-II: 8, Grade III: 4, and Grade-IV: 4. Laparotomy was done in six cases. There was no mortality in our study. CONCLUSION: The tragedy of septic-induced abortion is totally preventable. It only needs definitive commitment to women's health by providing effective contraception, strengthening the family welfare services, and discouraging repeated terminations of pregnancy as contraceptive method. PMID- 25136173 TI - Labor Induction with 50 MUg Vaginal Misoprostol: Can We Reduce Induction-Delivery Intervals Safely? AB - OBJECTIVE: To compare the efficacy and safety profile of two methods of labor induction i.e., intracervical dinoprostone gel (0.5 mg 8 h) and misoprostol (50 MUg 4 h) for induction of labor in women with a poor Bishop's score. DESIGN: Observational study. STUDY PERIOD: January 1st, 2009 to December 31st, 2010. POPULATION: A total of 329 women with unfavorable cervices induced at or near term. METHODS: Two cervical ripening agent study arms were used: dinoprostone gel (193 women) and misoprostol (137 women). MAIN OUTCOME MEASURES: Induction to delivery interval, cesarean section, incidence of meconium stained liquor, FHR pattern, incidence of uterine hyperstimulation, and neonatal outcomes. RESULTS: The induction to delivery interval was significantly shorter in the misoprostol group as compared to the dinoprostone group (p < 0.001). There was no difference in cesarean section rates between the two groups (dinoprostone gel 43 %; misoprostol 33 %; p = 0.144). The incidence of non-reassuring fetal heart rate pattern, meconium stained liquor, and uterine hyperstimulation were equivalent in both the groups (p = 0.529; 0.733; and 0.321, respectively). The neonatal outcomes in both the groups were comparable in terms of Apgar scores at birth (p = 0.160) and NICU admissions (p = 0.951). CONCLUSIONS: Labor induction in women with unfavorable cervices results in high caesarean section rates. However, the use of misoprostol significantly reduces the induction to delivery interval, without adversely affecting the caesarean section rates and neonatal outcomes. Hence it may become a cost-effective alternative to dinoprostone gel in resource poor settings like India. PMID- 25136174 TI - Urogenital infections as a risk factor for preterm labor: a hospital-based case control study. AB - PURPOSE: Preterm labor is a leading cause of neonatal morbidity and mortality. Ascending lower genital tract infection leads to preterm labor and adverse pregnancy outcomes. This prospective case-control study was performed to see the association between preterm labor and urogenital infections. METHODS: A total of 104 women were observed for urogenital infections and their association with preterm labor. Case Group I included 52 women with preterm labor after 26 weeks and before 37 completed weeks of gestation with or without rupture of membranes. Control Group II included 52 women at completed or more than 37 weeks of gestation with no history of preterm labor, matched to the case group with respect to age and parity. Midstream urine was sent for cytology and culture sensitivity. Samples from posterior fornix of vagina were taken with two sterilized swabs under direct vision using Cusco/Sims speculum before first vaginal examination and were studied for gram stain characteristics and culture sensitivity by standard methods. Microorganisms isolated on culture were noted, and antibiotics were given according to sensitivity. Data collected were analyzed according to the groups by chi(2) test for categorical variables. RESULTS: In our study, urogenital infection was seen in 19 women in Case Group I (36.54 %) compared with 9 women in Control Group (17.3 %), and the difference was statistically significant (p 0.027). CONCLUSION: Recognizing and treating the women having urogenital infections at a stage, when it has not become clinically evident, will decrease the percentage of women going into preterm labor and will improve the perinatal outcome. PMID- 25136175 TI - Prevalence and clinical utility of human papilloma virus genotyping in patients with cervical lesions. AB - OBJECTIVE: Cervical cancer is the commonest cancer among Indian women. High-risk human papilloma virus (HPV) detection holds the potential to be used as a tool to identify women, at risk of subsequent development of cervical cancer. There is a pressing need to identify prevalence of asymptomatic cervical HPV infection in local population. In our study, we explored the prevalence of HPV genotypes and their distribution in women with cervical lesions. METHODS: Scrape specimens were obtained from 100 women (study group) with cervical abnormalities. HPV was detected with amplicor HPV tests, and the individual genotypes in these specimens were identified by Hybribio Genoarray test kit. Fifty specimens were also collected from females with healthy cervix (control group). The present study also aimed to determine the status of HPV prevalence and its association with different sociodemographic factors. RESULTS: Out of the total number of 100 samples, 10 (10 %) women tested positive for HPV DNA. Among them, HPV 18 was observed in 6, HPV 16 in 2, HPV 52 and HPV 39 in one each. Fifty specimens collected from patients with healthy cervix were not infected with any of the HPV genotype. CONCLUSIONS: Our study generates data of HPV prevalence in patients with cervical lesions visiting tertiary care institute. The data generated will be useful for laying guidelines for mass screening of HPV detection, treatment, and prophylaxis. PMID- 25136176 TI - Correlation of Cytology and Colposcopic Findings Using Reid's Index in VIA Positive Women. AB - INTRODUCTION: Cervical cancer is the most common cancer among Indian women. Only 5 % of women in developing countries have ever been screened for cervical abnormalities. OBJECTIVES: To study the correlation of cytology and colposcopy in VIA-positive women attending the Gynaecology clinic. MATERIALS AND METHODS: This prospective cross-sectional study on 200 symptomatic women compares the role of cytology and colposcopy in the assessment of subjects testing positive for acetowhite lesions on the cervix after application of 5 % acetic acid (VIA). RESULTS: 200/637 women screened in OPD tested VIA positive, giving a positivity rate of 31 %. Six smears were reported as LGSIL or HGSIL giving a cytological abnormality rate of 3 %. The association between cytology and Reid's score was statistically significant at a p value of 0.02. Of the 4 cases with biopsy confirmed invasive cancer, cytology reported 2 as LGSIL and 2 as HGSIL. Colposcopy reported all these women as CIN 2/3. CONCLUSION: The accuracies of Pap smear cytology and colposcopy in the diagnosis of precancerous and cancerous lesions of cervix were good. PMID- 25136177 TI - Conservative management of interstitial pregnancy. PMID- 25136178 TI - Severe hemolytic disease of newborn in a rh d-positive mother: time to mandate the antenatal antibody screening. PMID- 25136179 TI - Residual adherent placenta with bladder injury: can we use methotrexate? PMID- 25136180 TI - A rare case of criminal abortion with retained foreign body in uterus for 2 years. PMID- 25136181 TI - Successful Pregnancy with Endometrial Stromal Sarcoma (ESS). PMID- 25136183 TI - Office Hysteroscopy: TROPHYscope CAMPO Compact Hysteroscope ((r)): Manufacturer: KARL STORZ, Tuttlingen, Germany. PMID- 25136182 TI - Diagnosing GDM: Role of Simple, Cost Effective, and Sensitive DIPSI Test. PMID- 25136184 TI - Scrub typhus: Emerging cause of multiorgan dysfunction. PMID- 25136185 TI - Noninvasive ventilation success: Combining knowledge and experience. PMID- 25136186 TI - Optimum positive end-expiratory pressure 40 years later. PMID- 25136187 TI - Profile of organ dysfunction and predictors of mortality in severe scrub typhus infection requiring intensive care admission. AB - BACKGROUND AND AIMS: Scrub typhus, a zoonotic rickettsial infection, is an important reason for intensive care unit (ICU) admission in the Indian subcontinent. We describe the clinical profile, organ dysfunction, and predictors of mortality of severe scrub typhus infection. MATERIALS AND METHODS: Retrospective study of patients admitted with scrub typhus infection to a tertiary care university affiliated teaching hospital in India during a 21-month period. RESULTS: The cohort (n = 116) aged 40.0 +/- 15.2 years (mean +/- SD), presented 8.5 +/- 4.4 days after symptom onset. Common symptoms included fever (100%), breathlessness (68.5%), and altered mental status (25.5%). Forty-seven (41.6%) patients had an eschar. Admission APACHE-II score was 19.6 +/- 8.2. Ninety-one (85.2%) patients had dysfunction of 3 or more organ systems. Respiratory (96.6%) and hematological (86.2%) dysfunction were frequent. Mechanical ventilation was required in 102 (87.9%) patients, of whom 14 (12.1%) were solely managed with non-invasive ventilation. Thirteen patients (11.2%) required dialysis. Duration of hospital stay was 10.7 +/- 9.7 days. Actual hospital mortality (24.1%) was less than predicted APACHE-II mortality (36%; 95% Confidence interval 32-41). APACHE-II score and duration of fever were independently associated with mortality on logistic regression analysis. CONCLUSIONS: In this cohort of severe scrub typhus infection with multi-organ dysfunction, survival was good despite high severity of illness scores. APACHE-II score and duration of fever independently predicted mortality. PMID- 25136188 TI - Noninvasive ventilation: Are we overdoing it? AB - BACKGROUND: Use of noninvasive ventilation (NIV) outside guideline recommendations is common. We audited use of NIV in our tertiary care critical care unit (CCU) to evaluate appropriateness of use and patient outcomes when used outside level I recommendations. MATERIALS AND METHODS: Prospective observational study of all patients requiring NIV. Clinical parameters and arterial blood gases were recorded at initiation of NIV and 2 h later (or earlier if clinically warranted). NIV titration and decision to intubate were left to the discretion of treating intensivist. Patients were categorized into two groups: Group 1: Those with level I indications for use of NIV and group 2: All other levels of indications. Patients were followed until hospital discharge. RESULTS: From January 2010 to June 2010, 1120 patients were admitted to the CCU. Of these 106 patients required NIV support with 40.6% (n = 43/106) being in group 1 and 59.4% (n = 63/106) in group 2. Of these 35.8% patients (38/106) failed NIV and required endotracheal intubation. NIV failure rates (41.27% vs. 27.91%; P = 0.02) and mortality (30.6% vs. 18.6%; P = 0.03) were significantly higher in group 2 patients. In a logistic regression analysis Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.02), time on NIV before intubation (P = 0.001) and baseline PaCO2 levels (P = 0.01) were strongly associated with mortality. CONCLUSION: Noninvasive ventilation failure and mortality rates were significantly higher when used outside level I recommendations. APACHE II score, baseline PaCO2 and duration on NIV prior to intubation were predictors of increased mortality. PMID- 25136189 TI - Compliance versus dead space for optimum positive end expiratory pressure determination in acute respiratory distress syndrome. AB - OBJECTIVE: To Compare compliance versus dead space (Vd) targeted positive end expiratory pressure (PEEP) as regard its effect on lung mechanics and oxygenation. MATERIALS AND METHODS: This study was carried out on 30 adult acute respiratory distress syndrome patients. The ventilator was initially set on volume controlled with tidal volume (Vt) 7 mL/kg predicted body weight (PBW), inspiratory plateau pressure (Ppl) <30 cm H2 O. If the Ppl was >30 cm H2 O with a TV of 6 mL/kg PBW, a step-wise Vt reduction of 1 mL/kg PBW to as low as 4 mL/kg/PBW was allowed. Respiratory rate adjusted to maintain pH 7.30-7.45. FiO2 start at 100%. Best PEEP determined at 2 points, one by titrating PEEP until reaching the highest static compliance (Cst) (PEEP Cst) and the other one is at the lowest Vd/Vt (PEEP Vd/Vt). The following data measured before and 30 min after setting PEEP Cst and PEEP Vd/Vt. Cst, PaCO2 - PetCO2, Vd/Vt, PaO2 /FiO2, Ppl, heart rate, mean arterial pressure and oxygen saturation. RESULTS: optimum PEEP determined by Vd/Vt was significantly (P < 0.05) lower than the optimum PEEP determined by Cst. Best PEEP Vd/Vt showed a significant decrease (P < 0.05) in Cst, PaCO2 - PetCO2, Vd/Vt and Ppl in comparison with best PEEP Cst. The PaO2 /FiO2 showed a significant increase (P < 0.05) with best PEEP Vd/Vt in comparison with best PEEP Cst. CONCLUSION: Vd guided PEEP improved compliance and oxygenation with less Ppl. Hence, its use as a guide for best PEEP determination may be useful. PMID- 25136190 TI - Funding sources for continuing medical education: An observational study. AB - AIMS: Medical accreditation bodies and licensing authorities are increasingly mandating continuing medical education (CME) credits for maintenance of licensure of healthcare providers. However, the costs involved in participating in these CME activities are often substantial and may be a major deterrent in obtaining these mandatory credits. It is assumed that healthcare providers often obtain sponsorship from their institutions or third party payers (i.e. pharmaceutical industry) to attend these educational activities. Data currently does not exist exploring the funding sources for CME activities in India. In this study, we examine the relative proportion of CME activities sponsored by self, institution and the pharmaceutical-industry. We also wanted to explore the characteristics of courses that have a high proportion of self-sponsorship. MATERIALS AND METHODS: This is a retrospective audit of the data during the year 2009 conducted at an autonomous clinical training academy. The details of the sponsor of each CME activity were collected from an existing database. Participants were subsequently categorized as sponsored by self, sponsored by institution or sponsored by pharmaceutical-industry. RESULTS: In the year 2009, a total of 2235 participants attended 40 different CME activities at the training academy. Of the total participants, 881 (39.4%) were sponsored by self, 898 (40.2%) were sponsored by institution and 456 (20.3%) by pharmaceutical-industry. About 47.8% participants attended courses that carried an international accreditation. For the courses that offer international accreditation, 63.3% were sponsored by self, 34.9% were sponsored by institution and 1.6% were sponsored by pharmaceutical-industry. There were 126 participants (5.6%) who returned to the academy for another CME activity during the study period. Self-sponsored (SS) candidates were more likely to sponsor themselves again for subsequent CME activity compared with the other two groups (P < 0.001). CONCLUSIONS: In our study, majority of healthcare professionals attending CME activities were either self or institution sponsored. There was a greater inclination for self-sponsoring for activities with international accreditation. SS candidates were more likely to sponsor themselves again for subsequent CME activities. PMID- 25136193 TI - Successful use of sustained low efficiency dialysis in a case of severe phenobarbital poisoning. AB - A 30-year-old female presented with coma and subsequent cardiac arrest caused by phenobarbital overdosage, requiring ventilatory and vasopressor support. She had also developed severe hypoxia following gastric aspiration. Initial therapy, including activated charcoal and forced alkaline diuresis, failed to significantly lower her drug levels and there was minimal neurological improvement. As she was hemodynamically unstable, and unsuitable for conventional dialysis, she was put on sustained low efficiency dialysis (SLED) to facilitate drug removal. SLED resulted in marked reduction in plasma level of phenobarbital, which eventually led to early extubation, improved cognition and aided full recovery. Thus, we concluded that SLED can be an effective alternative in cases of severe phenobarbital poisoning, where conventional hemodialysis or hemoperfusion cannot be initiated, to hasten drug elimination and facilitate early recovery. PMID- 25136192 TI - Hyperkalemic paralysis in primary adrenal insufficiency. AB - Hyperkalemic paralysis due to Addison's disease is rare, and potentially life threatening entity presenting with flaccid motor weakness. This case under discussion highlights Hyperkalemic paralysis as initial symptomatic manifestation of primary adrenal insufficiency. PMID- 25136194 TI - An unusual cause of gastrointestinal bleed. AB - Gastrointestinal (GI) bleed often brings the patient to the emergency medical service with great anxiety. Known common causes of GI bleed include ulcers, varices, Mallory-Weiss among others. All causes of GI bleed should be considered however unusual during the evaluation. Aortoenteric fistula (AEF) is one of the unusual causes of GI bleed, which has to be considered especially in patients with a history of abdominal surgery in general and aortic surgery in particular. PMID- 25136191 TI - Pediatric acute kidney injury: A syndrome under paradigm shift. AB - The recent standardization and validation of definitions of pediatric acute kidney injury (pAKI) has ignited new dimensions of pAKI epidemiology and its risk factors. pAKI causes increased morbidity and mortality in critically ill children. Among the hospitalized patients incidence of pAKI ranges from 1% to 31%, while mortality ranges from 28% to 82%, presenting a broad range due to lack of uniformly acceptable pAKI definition. In addition, cumulative data regarding the progression of pAKI to chronic kidney disease in children is rising. Despite these alarming figures, treatment modalities have failed to deliver significantly. In this review, we will summarize the latest developments of pAKI and highlight important aspects of pAKI management. PMID- 25136195 TI - Spontaneous cryptococcal peritonitis with fungemia in patients with decompensated cirrhosis: Report of two cases. AB - Cryptococcus neoformans is encapsulated yeast that predominately infects immunocompromised individuals. Liver disease is an under-recognized predisposition for cryptococcal disease. We report two nonalcoholic, nondiabetic, and human immunodeficiency virus - negative cirrhotic patients, with spontaneous cryptococcal peritonitis. Cryptococcus infection was diagnosed by culture of ascitic fluid and peripheral blood in both. We treated the first patient with amphotericin-B, but he expired. The second patient with earlier diagnosis, survived to discharge with fluconazole treatment. We suggest a high clinical suspicion for Cryptococcus as a possible etiology of spontaneous peritonitis in cirrhotic patients. PMID- 25136196 TI - Deep vein thrombosis of upper extremities due to reactive thrombocytosis in septic patients. AB - Deep venous thrombosis (DVT) is not an uncommon condition in the intensive care unit (ICU), and having high morbidity and mortality. Upper limb DVT also is increasingly being recognized as a clinical entity. The presence of the indwelling catheter in neck veins is a risk for developing venous thrombus, which may be further aggravated by presence of thrombocytosis. In ICU patients with sepsis, reactive thrombocytosis has been found during the recovery phase. Here, we are presenting two cases, having thrombocytosis and central venous catheter who developed upper limb DVT. PMID- 25136197 TI - Multinodular goiter with retrosternal extension causing airway obstruction: Management in intensive care unit and operating room. PMID- 25136198 TI - Management of snake bite victims in a Tertiary Care Intensive Care Unit in North India. PMID- 25136199 TI - Ofloxacin-induced toxic epidermal necrolysis. PMID- 25136200 TI - Internal jugular vein thrombosis from rhino-cerebral mucormycosis: Be careful before cannulation. PMID- 25136201 TI - Vasovagal syncope during spirometric exercise. PMID- 25136202 TI - Acute epiglottitis from corrosive ingestion. PMID- 25136203 TI - Application of rapid ultrasound in shock protocol in the ICU for management of shock. PMID- 25136205 TI - The dynamics and power of change: changing practices in cutaneous and aesthetic surgery. PMID- 25136207 TI - Management of infantile hemangiomas. PMID- 25136206 TI - Management of infantile hemangiomas: current trends. AB - Infantile hemangiomas (IH) are common vascular tumours. IH have a characteristic natural course. They proliferate rapidly during the early infantile period followed by a period of gradual regression over several years. Most of the uncomplicated IH undergo spontaneous involution, with a small proportion of cases requiring intervention. These are children with IH in life-threatening locations, local complications like haemorrhage, ulceration and necrosis and functional or cosmetic disfigurements. Systemic corticosteroids have been the first line of treatment for many years. Recently, non-selective beta-blockers, such as oral propranalol and topical timolol, have emerged as promising and safer therapies. Other treatment options include interferon alpha and vincristine which are reserved for life-threatening haemangiomas that are unresponsive to conventional therapy. This review mainly focuses on the current trends and evidence-based approach in the management of IH. PMID- 25136208 TI - Fractional CO2 Laser Resurfacing as Monotherapy in the Treatment of Atrophic Facial Acne Scars. AB - BACKGROUND: While laser resurfacing remains the most effective treatment option for atrophic acne scars, the high incidence of post-treatment adverse effects limits its use. Fractional laser photothermolysis attempts to overcome these limitations of laser resurfacing by creating microscopic zones of injury to the dermis with skip areas in between. AIM: The aim of the present study is to assess the efficacy and safety of fractional CO2 laser resurfacing in atrophic facial acne scars. MATERIALS AND METHODS: Sixty patients with moderate to severe atrophic facial acne scars were treated with 3-4 sessions of fractional CO2 laser resurfacing at 6-week intervals. The therapeutic response to treatment was assessed at each follow up visit and then finally 6 months after the last laser session using a quartile grading scale. Response to treatment was labelled as 'excellent' if there was >50% improvement in scar appearance and texture of skin on the grading scale while 25-50% response and <25% improvement were labelled as 'good' and 'poor' response, respectively. The overall satisfaction of the patients and any adverse reactions to the treatment were also noted. RESULTS: Most of the patients showed a combination of different morphological types of acne scars. At the time of final assessment 6 months after the last laser session, an excellent response was observed in 26 patients (43.3%) while 15 (25%) and 19 patients (31.7%) demonstrated a good and poor response respectively. Rolling and superficial boxcar scars responded the best while pitted scars responded the least to fractional laser monotherapy. The commonest reported adverse effect was transient erythema and crusting lasting for an average of 3-4 and 4-6 days, respectively while three patients developed post-inflammatory pigmentation lasting for 8-12 weeks. CONCLUSIONS: Fractional laser resurfacing as monotherapy is effective in treating acne scars especially rolling and superficial boxcar scars with minimal adverse effects. PMID- 25136210 TI - Efficacy of triple therapy in auricular keloids. AB - BACKGROUND: Keloids are characterised by their continued growth following trauma, extension into normal tissue and their high recurrence rate following excision. Auricular keloids are common following ear piercing or flame burns. These lesions are highly conspicuous and cosmetically unappealing. Multiple methods including surgery, radiotherapy, antimitotic agents, silicone sheet, pressure clips and cryotherapy have been advocated. The risk of recurrence and the need to prevent distortion of the three-dimensional structure of the ear following resection is a challenge to the cutaneous surgeon. OBJECTIVES: To devise a standard protocol for management of auricular keloids with minimal distortion and recurrence. SETTING AND DESIGN: The patients underwent day-care surgery and subsequent out-patient follow-up for a minimum period of 1 year. METHODS: Ten patients presenting with 22 ear keloids were enrolled into a keloid protocol: (a) surgical excision and keloid rind flap cover with (b) intra-operative and post-operative intra-lesional steroid and (c) silicone sheet application. Subjective assessment on follow-up was using Patient Observer Scar Assessment Scale and objective assessment was by Beausang scale. STATISTICAL ANALYSIS USED: Microsoft Excel and Statistical Package for the Social Sciences (SPSS). Kaplan-Meier survival analysis curve used to calculate Recurrence Free period. RESULTS: Two out of 22 (9.1%) keloids developed post-excision recurrence after a mean follow -up period of 16 months. The average keloid recurrence free interval was 21 months. CONCLUSION: Triple combination therapy for keloids on the ear is a simple technique for management with preservation of contour of the ear and a low recurrence rate. PMID- 25136209 TI - Evaluation of microneedling fractional radiofrequency device for treatment of acne scars. AB - BACKGROUND: Various treatment modalities including non-invasive methods such as chemical peels, topical retinoids, microdermabrasion, minimally invasive techniques such as microneedling, fractional lasers, microneedling radiofrequency devices and invasive procedures such as acne scar surgeries and ablative lasers are used for acne scars, each with its own unique advantages and disadvantages. This study is a retrospective assessment of efficacy and safety of microneedling fractional radiofrequency in the treatment of acne scars. METHODS: Thirty one patients of skin types III-V with moderate and severe facial acne scarring received four sequential fractional radiofrequency treatments over a period of 6 months with an interval of 6 weeks between each session. Goodman & Baron's acne scar grading system was used for assessment by a side by side comparison of preoperative and post- operative photographs taken at their first visit and at the end of 3 months after the last session. RESULTS: Estimation of improvement with Goodman and Baron's Global Acne Scarring System showed that by qualitative assessment of 31 patients with grade 3 and grade 4 acne scars, 80.64% showed improvement by 2 grades and 19.35% showed improvement by 1 grade. Quantitative assessment showed that 58% of the patients had moderate, 29% had minimal, 9% had good and 3% showed very good improvement. Adverse effects were limited to transient pain, erythema, edema and hyperpigmentation. CONCLUSION: Microneedling fractional radiofrequency is efficacious for the treatment of moderate and severe acne scars. PMID- 25136211 TI - Outcomes of staple closure of the donor area during hair transplant by follicular unit transfer. AB - BACKGROUND: Donor area closure in hair transplantation by follicular unit transfer (FUT) is being done by various techniques. This study aims to assess the outcomes of staple closure for donor area in FUT. AIM: To study the outcome, efficacy and complications of staples in donor area closure for FUT. MATERIALS AND METHODS: A total of 50 consecutive patients who underwent staple closure for donor area in FUT were included in the study and their data were collected retrospectively. Patients were followed up one year after the surgery and photographic documentation of the scar at the donor site was done. Objective measurement of the width of the scar was done for all the patients. RESULTS: The average length of the donor area was 22 cm. The average width of the scar was 1.82 mm. There was no infection or tissue necrosis at the staple closure site in any of the patients. CONCLUSION: Staple closure resulted in cosmetically acceptable scar, but post operative discomfort was the major limitation. The potential to conserve the hair follicles along the line of closure makes using staples worthwhile if conservation of follicles is the goal. PMID- 25136212 TI - Platelet-rich plasma in androgenic alopecia: myth or an effective tool. AB - Platelet-rich plasma (PRP) has become a newer method for the treatment of various types of alopecia. In this prospective study, safety, efficacy and feasibility of PRP injections in treating androgenic alopecia were assessed. Eleven patients suffering from hair loss due to androgenic alopecia and not responding to 6 months treatment with minoxidil and finasteride were included in this study. The hair pull test was performed before every treatment session. A total volume of 2 3 cc PRP was injected in the scalp by using an insulin syringe. The treatment was repeated every two weeks, for a total of four times. The outcome was assessed after 3 months by clinical examination, macroscopic photos, hair pull test and patient's overall satisfaction. RESULTS: A significant reduction in hair loss was observed between first and fourth injection. Hair count increased from average number of 71 hair follicular units to 93 hair follicular units. Therefore, average mean gain is 22.09 follicular units per cm(2.) After the fourth session, the pull test was negative in 9 patients. CONCLUSION: PRP injection is a simple, cost effective and feasible treatment option for androgenic alopecia, with high overall patient satisfaction. PMID- 25136213 TI - Platelet Rich Plasma in Androgenic Alopecia: Where do we Stand? PMID- 25136215 TI - Gynaecomastia Surgery: Should it be Individualised? PMID- 25136214 TI - Role of Combined Circumareolar Skin Excision and Liposuction in Management of High grade Gynaecomastia. AB - INTRODUCTION: High-grade gynaecomastia (Simon IIb and III) has tissue excess (skin excess, enlarged areola, and displaced nipple), which is best managed surgically; however, results of conventional breast reduction surgeries and liposuction is not very good. Aim of our study was to describe a combined technique to manage these problems to produce a good result. MATERIAL AND METHOD: This was a 2-year study among 12 patients of high grade gynaecomastia. Clinical and laboratory findings were normal. Pre-operatively in standing position, diameter of breast and areola, position of nipple, and amount of skin excess were marked. Under general anaesthesia, tumescent infiltration, circumareolar de epithelisation of skin excess, and liposuction was completed. Redundant portion of the breast was sharply dissected and pulled out. Areola was fixed over pectoralis fascia at mid humerus level, just medial to the mid-clavicular line. Outer borders of the de-epithelised area were apposed by the purse-string effect of a subdermal suture, and further apposed by few half buried horizontal mattress sutures. Drains for 24 hour and compressive dressings for 6 weeks were used. RESULT: Mean age of presentation was 25.8 year; emotional discomfort was the chief complaint. Among 12 patients, 10 patients had bilateral gynaecomastia and 8 patients had enlarged and displaced nipple-areola complex. Average hospital stay was 2.41 days and recoveries were usually uneventful. CONCLUSION: The problem of tissue excess and tissue displacement in high grade gynaecomastia can be well managed by this combined circumareolar skin reduction and liposuction technique to achieve a scar-less flat male chest. PMID- 25136216 TI - Targeted cryotherapy using disposable biopsy punches. AB - Cryotherapy is a commonly used office procedure that causes destruction of tissue by cryonecrosis due to rapid freezing and thawing of cells. The limitation in treating plantar warts and deeper dermal lesions is that the freeze time should be longer to penetrate deeper, which results in collateral damage to normal skin surrounding the lesion. This results in unwanted side effects of prolonged pain, blistering and haemorrhage and increased healing time. The cone spray technique was used to reduce collateral damage, but deeper penetration is difficult to achieve. An innovative technique using disposable biopsy punches is described that ensures deeper freezing as compared to the plastic cone. The metal cutting edge of the punch enters deeper into the lesions as the liquid nitrogen is passed, sparing damage to surrounding skin. PMID- 25136217 TI - How to practice dermatosurgery safely? AB - Dermatosurgery has become an integral and essential component of current dermatology practice. No surgery can be totally risk free, only the level of risk varies. Patient safety has to be ensured by following standard protocols and taking appropriate precautions to prevent complications and mishaps. Mismatch between patient's expectations and outcome can lead to litigation. A dermatosurgeon should take care of his legal safety by obtaining informed consent and meticulously documenting and preserving medical records. Importance of communication and maintaining of fiduciary relationship with the patient cannot be overemphasized. PMID- 25136218 TI - Buying a laser - tips and pearls. AB - Lasers and aesthetic procedures have transformed dermatology practice. They have aided in the treatment of hitherto untreatable conditions and allowed better financial remuneration to the physician. The availability of a variety of laser devices of different makes, specifications and pricing has lead to confusion and dilemma in the mind of the buying physician. There are presently no guidelines available for buying a laser. Since purchase of a laser involves large investments, careful consideration to laser specifications, training, costing, warranty, availability of spares, and reliability of service are important prerequisites. This article describes various factors that are needed to be considered and also attempts to lay down criteria to be assessed while buying a laser system that will be useful to physicians before investing in a laser machine. PRACTICE POINTS: Meticulous planning of the type of machine, specifications, financial aspects, maintenance and warranties is important.It is wise to sign a contract or agreement between the buyer and seller before purchase of a laser which covers key aspects of installation, after sales service and maintenance of the machine.Adequate training is essential; understanding laser physics and laser-tissue interaction goes a long way in getting the best out of the machine.The credibility of the dealer and company should be ascertained in order to be assured of after-sales service.Buying used machines, sharing of equipment to offset high initial investments is a good option but even more care is required to ensure proper functioning and maintenance. PMID- 25136220 TI - Favre-racouchot syndrome with bilateral mechanical ptosis: an unusual presentation. PMID- 25136219 TI - Primary Bilateral Extramammary Paget's Disease of the Axillae: Another Case of this Strange Disease. AB - Primary extramammary Paget's disease of the axilla is a rare variant with the capability of mimicking other more common conditions. We present a case of a 65 year-old woman with inflammatory skin lesions of both axillae clinically unresponsive to long-term conventional topical therapy. We decided to excise and reconstruct the resulting soft tissue defect of the major lesion by using a thoraco-dorsal artery perforator-based Limberg's flap. The histopathological examination showed intracellular mucin, signet cells, and glandular structures, the typical pattern of the EMPD. This was a very interesting case of a per se rare condition. PMID- 25136221 TI - Re: superficial large Basal cell carcinoma over face, reconstructed by v-y plasty. PMID- 25136222 TI - Author's reply. PMID- 25136223 TI - Re: Propranolol for infantile haemangiomas: Early experience from a tertiary center. PMID- 25136224 TI - Author's reply. PMID- 25136225 TI - Reply to expert comments - a study of donor area in follicular unit hair transplantation. PMID- 25136226 TI - Cavitary anomalies of the optic disc: Different entities or part of a single spectrum of disease? PMID- 25136227 TI - Non-drainage scleral buckling with solid silicone elements. AB - BACKGROUND: With the increasing number of cataract surgeries, incidence of posterior segment complications including rhegmatogenous retinal detachment (RRD) is likely to rise. Scleral buckling (SB) surgery is an effective and less expensive option. The primary advantage of non-drainage procedure is avoidance of possible complications associated with trans-choroidal drainage. The aim of present study is to describe the clinical profile of subjects undergoing non drainage SB surgery with solid silicone elements for RRD and analyze their treatment outcomes. MATERIALS AND METHODS: This was a retrospective, non randomized, interventional study at a tertiary care center. Three hundred and six eyes of 298 patients undergoing non-drainage SB surgery with solid silicone elements from year 2000 to 2006 were included. Inclusion criteria were primary RRD, peripheral depressible retinal break, media clarity affording peripheral retinal view and proliferative vitreo-retinopathy (PVR) up to grade C2. Uni- and multivariate analyses was done to analyze factors affecting anatomical and visual outcomes. Statistical analysis was performed using SPSS Version 10. RESULTS: Mean follow-up was 303 +/- 393.33 days. Primary anatomical success was obtained in 279 (91.2%) eyes; primary functional success in 286 (93.5%) eyes. PVR (grade B or C), intraocular pressure <10 mm Hg and the inability to find a retinal break were significantly associated with final anatomical failure. Baseline vision <=3/60 was significantly associated with poor visual recovery. CONCLUSIONS: SB surgery is reasonably safe and highly efficacious. Solid silicone elements are effective in non-drainage SB surgery. However, case selection is important. PMID- 25136228 TI - Botulinum neurotoxin type A versus punctal plug insertion in the management of dry eye disease. AB - PURPOSE: To compare the efficacies of punctal plug insertion and Botulinum toxin injection in dry eye disease not responding to topical medications. MATERIALS AND METHODS: A non-controlled randomized clinical trial of two parallel groups of 60 dry eye patients seen in the clinic not responding to topical medications were divided into two groups. One group received punctal plugs and the other group received Botulinum toxin injections to prevent lacrimal tear drainage. RESULTS: Of a total of 36 patients with a mean age of 44.5 years who received punctal plugs, 50% of them experienced improvements in the clinical manifestations of their disease. 12/36 (33.3%) developed plug extrusion, and 6/36 (16.7%) patients developed conjunctival erosions with irritation that necessitated plug removal within one week of insertion. A total of 24 patients with a mean age of 47.5 years received injections of Botulinum toxin. Of these, 83.3% had improvement in all of the clinical manifestations of dry eye. 4/24 (16.7%) had no improvement in the degrees to which they experienced foreign body sensations, 33.3% reported shampoo entering the eye while showering. All of the patients who received Botulinum toxin injections were satisfied with the results of their treatment, whereas only 72.3% of the patients who received punctal plugs were satisfied with their results. CONCLUSION: Botulinum neurotoxin A injections can be a very good alternative to punctal plugs in improving the clinical manifestations of dry eye disease They are associated with the development of fewer and milder complications and with higher levels of patient satisfaction. PMID- 25136229 TI - Ancient schwannoma of the orbit. AB - The ancient schwannoma is a rare variant of a neurilemoma with a course typical of a slow-growing benign neoplasm. Histologically, it can be confused with a malignant mesenchymal tumor because of increased cellularity, nuclear pleomorphism, and hyperchromatism. Despite the degree of nuclear atypia, mitotic figures are absent. We describe the clinical and histopathologic features of an ancient schwannoma of the orbit. A need for early removal of such tumors is recommended to prevent complications. PMID- 25136230 TI - Cornelia de Lange syndrome with optic disk pit: Novel association and review of literature. AB - Cornelia de Lange syndrome (CdLS), also called Brachmann-de Lange syndrome, is a multiple congenital anomaly syndrome characterized by a distinctive facial appearance, ophthalmological abnormalities, prenatal and postnatal growth deficiency, psychomotor delay, behavioral problems, and malformations of the upper extremities. Most common and consistent ophthalmic features reported are nasolacrimal duct obstruction, long and curly eyelashes, blepharitis, ptosis, synophrys, telecanthus, hypertelorism, microcornea, peripapillary pigment ring, and myopia. In this report we report a case of a 5-year old boy who presented to our institution with complaint of blurring of vision in the right eye since birth. A diagnosis of Cornelia de Lange syndrome was arrived at based on the characteristic external and ophthalmic examination. He was found to have a rare association of optic nerve head coloboma in the right eye and a novel finding of an optic disk pit in the left eye. The association of optic disk pit with CdLS has never been reported earlier. We aim to provide a thorough review of literature of this not so uncommon syndrome. PMID- 25136231 TI - Bilateral simultaneous nonarteritic anterior ischemic optic neuropathy in a patient with alcoholic liver disease. AB - A 53-year-old man with a history of alcoholism since 10 years admitted for jaundice elsewhere developed bilateral simultaneous decrease in vision in both the eyes 4 days after admission. His best-corrected visual acuity was 20/20 in both eyes. Visual field evaluation revealed an inferior altitudinal defect in both the eyes. Optic disc appearance, visual fields, and optical coherence tomography of discs were suggestive of nonarteritic anterior ischemic optic neuropathy (NAION) in both the eyes. Liver function tests revealed elevated serum bilirubin and hepatic enzymes. He was negative for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Abdominal ultrasound revealed no focal hepatic lesion, and carotid doppler revealed no arteriosclerosis. A diagnosis of bilateral ischemic optic neuropathy associated with alcoholic hepatitis was made. Bilateral simultaneous NAION has been previously reported in perioperative visual loss, HCV infection, and interferon treatment. This is the first case report of bilateral simultaneous NAION in alcoholic hepatitis in the absence of associated infective viral hepatitis. We explore the pathophysiology of ischemic optic neuropathy in liver disease. An early intervention to correct the risk factors leading to NAION may help in preventing this vision-threatening complication in patients with chronic liver disease. PMID- 25136232 TI - Rapid regression of choroidal metastasis from lung cancer using erlotinib (Tarceva). AB - Lung carcinoma is the leading cause of cancer-related deaths and is the primary source for choroidal metastasis in over 20% cases. Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. Patients with metastatic NSCLC have a median survival of one year. Successful treatment of systemic metastasis from NSCLC using erlotinib has been documented. The effect of oral erlotinib on choroidal metastasis has been rarely reported. We document a case and study the effect of oral erlotinib on choroidal metastasis from NSCLC. A 48-year-old Caucasian female presented with biopsy-proven primary NSCLC with systemic metastasis and solitary choroidal metastasis of 4.8 mm thickness in the right eye. The patient was treated with 100 mg daily dose of oral erlotinib. Two weeks after starting erlotinib therapy, the patient showed complete regression of choroidal metastasis to a flat scar with resolution of subretinal fluid and improvement of visual acuity from 20/100 to 20/25. There was no evidence of recurrence at five-month follow-up. Erlotinib is an alternative therapy for choroidal metastasis from NSCLC. PMID- 25136233 TI - Long-term results of intravitreal ranibizumab for osteoma-related choroidal neovascularization in a child. AB - Though choroidal osteoma is a rare benign tumor, associated choroidal neovascularization (CNV) can be a cause of severe visual loss. A nine-year-old boy presented with one-month history of decreased vision in left eye. Upon a complete ophthalmologic examination, including fundus fluorescein angiography and optical coherence tomography, he was diagnosed with choroidal osteoma-related subfoveal CNV in the left eye. The CNV was associated with subretinal hemorrhage, subretinal fluid, and cystoid macular edema. Owing to the young age and subfoveal localization of the CNV, intravitreal ranibizumab injection was performed on this patient after a detailed discussion with the parents of its safety profile. No local or systemic complications were noted. No recurrence of CNV lesion was noted during 30 months of follow-up, and the vision was maintained. This report shows the favorable outcome of intravitreal injection of ranibizumab in choroidal osteoma-related CNV in a child. PMID- 25136235 TI - Optical coherence tomography demonstrating macular retinal nerve fiber thinning in advanced optic disc drusen. AB - Optic disc drusen (ODD) are extracellular proteinaceous excrescences in the optic nerve head. They enlarge over time and can cause damage to nerve fibers with resulting loss of visual field. The authors report a case of advanced ODD in which macular optical coherence tomography demonstrated retinal nerve fiber thinning. A single case report of a 42-year-old woman with known ODD presented to the eye clinic with worsening field of vision which was impacting on her daily life. The patient was subject to full ophthalmic examination as well as Goldmann visual field testing, optic disc photography and optical coherence tomography (OCT) of both her optic discs and maculae. ODD although rare, can be visually devastating. No treatment is currently available however patients should be counseled about progressive nature of ODD and the potential for visual loss. OCT imaging of the maculae as well as optic discs may serve a role in monitoring the damage disc drusen cause to the eye. PMID- 25136234 TI - Giant leiomyoma of the ciliary body. AB - Leiomyoma is a rare intraocular tumor that arises from uveal smooth muscle. Herein, we report a large leiomyoma that occupied nearly 50% of the globe, closely resembling melanoma. A 40-year-old female presented with a 17 * 15 * 11 mm amelanotic ciliochoroidal mass causing visual defect in her right eye (OD). Based on transillumination features of tumor shadow and ultrasonographic features of acoustically solid mass, there was low clinical suspicion for leiomyoma or schwannoma, and a preliminary diagnosis of ciliochoroidal melanoma was rendered. Following enucleation, histopathology revealed a paucicellular tumor comprised of spindle cells, with positive immunostaining for smooth muscle actin and negative stains for melanoma markers (S-100 protein, HMB45, and MITF-2). These features were consistent with ciliochoroidal leiomyoma. Benign uveal leiomyoma can achieve an unusually large size and block light transmission on transillumination, features that simulate malignant melanoma. PMID- 25136236 TI - Alternating central serous chorioretinopathy in two consecutive pregnancies. AB - To highlight the similarity in onset, clinical course, and resolution of central serous chorioretinopathy in two eyes, in two consecutive pregnancies in the same patient. A case report. Snellen visual acuity, slit-lamp examination, and optical coherence tomography (OCT). A 31-year-old female had central serous chorioretinopathy with sub-retinal exudates in left eye during the sixth month of her first pregnancy and later in right eye also during the sixth month of her second pregnancy two years later. Both eyes had spontaneous resolution of the lesions with final visual acuity of 1.0 each eye. To the best of our knowledge, there have been no reports of alternating CSCR with sub-retinal exudates, occurring exactly in the sixth month of two consecutive pregnancies, two years apart, with spontaneous resolution after deliveries. PMID- 25136238 TI - Medulloepithelioma: A triad of clinical features. AB - BACKGROUND: Intraocular medulloepithelioma arises from the primitive medullary epithelium and is diagnosed at a median age of five years. This tumor most commonly appears as a white, gray, or yellow-colored ciliary body tumor. The growth of medulloepithelioma is slow and it is locally invasive. Poor vision and pain are the most common presenting symptoms. The most common clinical signs include cyst or mass in iris, anterior chamber or ciliary body, glaucoma, and cataract. CASE: A 22-month-old Caucasian female twin presented with leukocoria and poor vision in OS. Examination revealed normal findings OD and a mass in OS. Based on the clinical features of leukocoria, lens changes and a white cystic ciliary body mass in a young child, ultrasonographic, and transillumination features, the lesion was diagnosed as a non-pigmented ciliary epithelial medulloepithelioma. After enucleation, the diagnosis of malignant teratoid medulloepithelioma of the non-pigmented ciliary epithelium was confirmed. There was no evidence of tumor recurrence or systemic metastasis at three years follow up. CONCLUSION: Medulloepithelioma in a child can present as a clinical triad of leukocoria, lens changes, and a white cystic ciliary body mass. PMID- 25136237 TI - OLOGEN((r)) implant in the management of glaucoma in an unusual case of Axenfeld Rieger syndrome. AB - We report an unusual case of Axenfeld-Rieger Syndrome with secondary glaucoma managed with Ologen((r)) implant. A 35-year-old male presented with complaints of decreased vision in both eyes of 22 years duration. His best corrected visual acuity (BCVA) was no perception of light in right eye and 20/30 in left eye. Gonioscopy revealed anterior insertion of iris into trabecular meshwork, prominent iris processes and broad-based synechiae with prominent Schwalbe's line along the angle circumference with cord-like structures taking its origin at the level of Schwalbe's line in both eyes. Fundus examination revealed total glaucomatous optic atrophy in right eye with 0.9:1 cup disc ratio with bipolar notch in left eye. Humphrey visual field analysis showed superior and inferior arcuate scotoma in left eye. Intraocular pressure measured by Goldman applanation tonometry was 30 mmHg and 26 mmHg in right and left eye, respectively. After an unsuccessful medical management, he underwent trabeculectomy with Ologen((r)) implant under local anesthesia in his left eye. Postoperatively, at the end of one year, intraocular pressure (IOP) in his left eye was controlled without medication. This case highlights the management of secondary angle closure glaucoma in Axenfeld-Rieger syndrome with Ologen((r)) implant. PMID- 25136239 TI - Branch retinal artery occlusion associated with congenital retinal macrovessel. AB - A congenital retinal macrovessel (CRM) is a large retinal vessel, usually a vein, which traverses through the central macula and has large tributaries extending on both sides of the horizontal raphe. In the majority of cases, CRM have no effect on visual acuity, although in rare cases, macular hemorrhage, foveolar cysts, serous macular detachment, and the presence of the anomalous vessel in the foveola can affect vision. We describe a case of CRM with decreased vision secondary to a branch retinal artery occlusion (BRAO). To the best of our knowledge, this association has not been reported previously. PMID- 25136240 TI - Congenital total eversion of upper eyelids in a newborn with Down's syndrome. PMID- 25136242 TI - Progressive Painless Loss of Vision - What is the diagnosis? PMID- 25136241 TI - Fundus autofluorescence imaging to document evolution, progression and healing pattern of serpiginous choroiditis. PMID- 25136243 TI - Complete third nerve palsy: Only presenting sign of extradural hematoma in an awake patient. PMID- 25136244 TI - Retinal pigment epithelial tear after intravitreal bevacizumab injection for exudative age-related macular degeneration. PMID- 25136245 TI - An unusual case of posterior cerebral artery infarct in otherwise healthy man. PMID- 25136247 TI - In-house drug diversion by hospital personnel. PMID- 25136246 TI - Comparison between helical computed tomography angiography and intraoperative findings. AB - BACKGROUND: Live donor nephrectomy has gained popularity on account of the laparoscopic technique, to overcome a small donor pool. Laparoscopic donor nephrectomy requires a precise study of the vascular and morphological renal anatomy, as laparoscopy is technically challenging due to the limited field of vision. In-depth knowledge of the renal anatomy before a laparoscopic procedure is essential for a successful transplant. The left kidney is preferred over the right even in cases of multiple vessels because of the long renal vein, which requires precise preoperative vascular mapping. Helical computerized tomography (CT) angiography, with its axial, coronal, and 3D reconstruction, gives a better understanding of renal anatomy. There are instances where the helical CT findings are misleading and less informative in a small number of cases. This study highlights a case study of the helical CT findings compared with the intraoperative findings of 200 live donors, who underwent laparoscopic donor nephrectomy, and the renal anatomy has been understood at the same time. AIMS: 1. To compare the helical CT findings on the operated side with the intraoperative findings. 2. To analyze the CT findings. MATERIALS AND METHODS: Two hundred cases of laparoscopic transperitoneal donor nephrectomy were included in this study. STATISTICAL METHOD USED: Chi square test was the statistical test used to compare the findings between CT and the intraoperative data. RESULTS: The axial, coronal, and 3D images of the CT findings were on par with the intraoperative findings in most of the cases. Incidental findings help in the better planning of surgery. Multiple vessels on the left side are preferred over the right sided normal anatomy; with not much technical difficulty with the aid of a helical CT. Male donors had more incidences of multiple vessels, gonadal vein, Retroaortic Renal Vein (RARV), lumbar vein, and duplication of ureter, compared to females. Furthermore, these variations are more in the left side donors. Ninety-two percent of the cases in this study are left-sided donors. The helical CT finding shows that renal vein variations are more on the right side. CONCLUSIONS: Helical CT is important in delineating the arterial, venous, and ureteral anatomy and can show the important incidental findings. Left renal donors and males have more variations in their renal anatomy. Technically challenging laparoscopic nephrectomy on the multiple-vessel-side donor is possible with the aid of helical CT. The importance of the CT in evaluating donor renal anatomy for a technically challenging laparoscopic donor nephrectomy is commendable. PMID- 25136248 TI - Oops, Sorry, Wrong Patient!: A Patient Verification Process is Needed Everywhere, Not Just at the Bedside. AB - Verification of patient identity is needed at all stages. PMID- 25136249 TI - HHS Alters Formulary Exception Policy for 2015: QHPs Must Respond Within 24 Hours to "Expedited" Requests. AB - HHS adjusts its formulary "exception" policy for 2015. PMID- 25136251 TI - Pharmaceutical approval update. AB - Vedolizumab (Entyvio) for ulcerative colitis and Crohn's disease; dalbavancin (Dalvance) for acute bacterial skin and skin structure infections; and antihemophilic factor, recombinant (Eloctate) for hemophilia A. PMID- 25136252 TI - Tedizolid phosphate (sivextro): a second-generation oxazolidinone to treat acute bacterial skin and skin structure infections. AB - Tedizolid phosphate: a second-generation oxazolidinone for acute bacterial skin and skin structure infections. PMID- 25136253 TI - Legal risk management opportunities, pharmacy practice, and p&t committees: part 1: deconstructing dispensing errors. AB - A comprehensive analysis of malpractice claims experience from a professional liability insurer, Healthcare Providers Service Organization, can help P&T committees better understand the risks and challenges they encounter each day. PMID- 25136254 TI - Are specialty drug prices destroying insurers and hurting consumers?: a number of efforts are under way to reduce price pressure. AB - Organizations are trying to address the high cost of "specialty" medications that treat conditions such as cancer, hepatitis C, and multiple sclerosis. While comprising less than 1% of U.S. prescriptions, these drugs now account for 27% of pharmacy spending. PMID- 25136256 TI - Ulcerative colitis and Crohn's disease. AB - As new drugs emerge from the pipeline for the nearly 2 billion patients globally diagnosed with ulcerative colitis and Crohn's disease, sales of therapies for these conditions are expected to increase from $7.35 billion today to $11.05 billion in 2022. PMID- 25136255 TI - Irritable bowel syndrome: current and emerging treatment options. AB - Irritable bowel syndrome, a functional gastrointestinal disorder of uncertain pathophysiology, affects up to 55 million Americans. Medications available or in development include antispasmodics, antidepressants, and antidiarrheals. PMID- 25136257 TI - Rosiglitazone enhances apolipoprotein M (Apom) expression in rat's liver. AB - Apolipoprotein M (APOM) has been suggested as a vasculoprotective constituent of high density lipoprotein (HDL), which plays a crucial role behind the mechanism of HDL-mediated anti-atherosclerosis. Previous studies demonstrated that insulin resistance could associate with decreased APOM expressions. In agreement with our previous reports, here, we further confirmed that the insulin sensitivity was also reduced in rats treated with high concentrations of glucose; such effect could be reversed by administration of rosiglitazone, a peroxisome proliferator activated receptor-gamma (PPARgamma). The present study shows that Apom expression is significantly affected by either rosiglitazone or hyperglycemia alone without cross interaction with each other, which indicates that the pathway of Apom expression regulating by hyperglycemia might be differed from that by rosiglitazone. Further study indicated that hyperglycemia could significantly inhibit mRNA levels of Lxrb (P=0.0002), small heterodimer partner 1 (Shp1) (P<0.0001), liver receptor homologue-1 (Lrh1) (P=0.0012), ATP-binding cassette transporter 1 (Abca1) (P=0.0012) and Pparb/d (P=0.0043). Two-way ANOVA analysis demonstrated that the interactions between rosiglitazone and infusion of 25% glucose solution on Shp1 (P=0.0054) and Abca1 (4E, P=0.0004) mRNA expression was statistically significant. It is concluded that rosiglitazone could increase Apom expression, of which the detailed mechanism needs to be further investigated. The downregulation of Apom by hyperglycemia might be mainly through decreasing expression of Pparg and followed by inhibiting Lxrb in rats. PMID- 25136258 TI - Three-dimensional culture environment increases the efficacy of platelet rich plasma releasate in prompting skin fibroblast differentiation and extracellular matrix formation. AB - Platelet rich plasma clot- releasate (PRCR) shows significant influence on tissue regeneration in clinical trials. Although, the mechanism of PRCR effect on fibroblast differentiation has been studied on 2D culture system, a detailed investigation is needed to establish the role of PRCR in cell seeded in 3D scaffolds. Therefore, a study was conducted to evaluate the influence of PRCR in fibroblasts (DFB) differentiation and extracellular matrix formation on both 3D and 2D culture systems. Cell viability was measured using MTT assay and DFB differentiation was evaluated by determining the expression levels of nucleostamin and alpha smooth muscle actin (alpha-SMA), using indirect immunostaining and Western blotting. The expression levels of extracellular matrix genes (collagen-I, collagen-III, fibronectin and laminin) and focal adhesion formation gene (integrin beta-1) were measured using Real-time PCR. The PRCR at 10% showed significant effect on cells viability compared with 5% and 20% in both culture environments. The decrease in the expression levels of nucleostamin and the increase in alpha-SMA signify the DFB differentiation to myofibroblast-like cells that was prominently greater in 3D compared to 2D culture. In 3D culture systems, the total collage production, expression levels of the extracellular matrix gene and the focal adhesion gene were increased significantly compared to 2D culture. In conclusion, 3D culture environments enhances the proliferative and differentiation effects of PRCR on DFB, thereby potentially increases the efficacy of DFB for future tissue engineering clinical application. PMID- 25136259 TI - Research progress on vertebrobasilar dolichoectasia. AB - Vertebrobasilar dolichoectasia (VBD) is a rare disease characterized by significant expansion, elongation, and tortuosity of the vertebrobasilar arteries. Current data regarding VBD are very limited. Here we systematically review VBD incidence, etiology, characteristics, clinical manifestations, treatment strategies, and prognosis. The exact incidence rate of VBD remains unclear, but is estimated to be 1.3% of the population. The occurrence of VBD is thought to be due to the cooperation of multiple factors, including congenital factors, infections and immune status, and degenerative diseases. The VBD clinical manifestations are complex with ischemic stroke as the most common, followed by progressive compression of cranial nerves and the brain stem, cerebral hemorrhage, and hydrocephalus. Treatment of VBD remains difficult. Currently, there are no precise and effective treatments, and available treatments mainly target the complications of VBD. With the development of stent technology, however, it may become an effective treatment for VBD. PMID- 25136260 TI - Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson's disease: a comparison study of mononuclear and mesenchymal stem cells. AB - The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the injury site and prevents neuronal damage after an MPTP infusion could be considered as a potential treatment for PD during the early stage of disease development. PMID- 25136263 TI - Insomnia among patients with advanced disease during admission in a Palliative Care Unit: a prospective observational study on its frequency and association with psychological, physical and environmental factors. AB - BACKGROUND: THE AIMS OF THIS STUDY WERE: 1) to assess the frequency of insomnia among patients during admission in a Palliative Care Unit (PCU); 2) to study the association between emotional distress and insomnia, taking physical, environmental and other psychological factors into account. METHODS: Prospective observational study including patients consecutively admitted to a PCU during eight months, excluding those with severe cognitive problems or too low performance status. Insomnia was assessed by asking a single question and by using the Sleep Disturbance Scale (SDS), and emotional distress using the Hospital Anxiety and Depression Scale (HADS). Physical, environmental and other psychological factors potentially interfering with sleep quality were evaluated. Association between insomnia and the factors evaluated was studied using univariate and multivariate regression analyses. RESULTS: 61 patients were included (mean age 71.5 years; 95% with oncological disease); 38 (62%) answered "yes" to the insomnia single question and 29 (47%) showed moderate to severe insomnia according to the SDS. 65% showed clinically significant emotional distress and 79% had nocturnal rumination. The physical symptoms most often mentioned as interfering with sleep quality were pain (69%) and dyspnoea (36%). 77% reported at least one environmental disturbance. In the univariate analysis, answering "yes" to the insomnia single question was significantly associated with higher HADS score, anxiety, nocturnal rumination, clear knowledge of the diagnosis, higher performance status and dyspnoea; moderate to severe insomnia was significantly associated with nocturnal rumination, higher performance status, environmental disturbances and daytime sleepiness. In the multivariate regression analysis, answering "yes" to the single question was associated with dyspnoea (OR 7.2 [1.65-31.27]; p = 0.009), nocturnal rumination (OR 5.5 [1.05 28.49]; p = 0.04) and higher performance status (OR 14.3 [1.62-125.43]; p = 0.017), and moderate to severe insomnia with nocturnal rumination (OR 5.6 [1.1 29.1]; p = 0.041), and inversely associated with daytime sleepiness (OR 0.25 [0.07-0.9]; p = 0.043). CONCLUSIONS: Insomnia was highly frequent. Several physical, psychological and environmental factors seemed to influence insomnia. Within the multimodal management of insomnia, the assessment of nocturnal rumination may be of particular interest, irrespective of emotional distress. Further studies with larger sample sizes could confirm this result. PMID- 25136261 TI - Bone morphogenetic protein-9 induces PDLSCs osteogenic differentiation through the ERK and p38 signal pathways. AB - Periodontal ligament stem cells (PDLSCs) with bone morphogenic ability are used to treat diseases such as periodontitis. Their treatment potential is increased when used in combination with proteins that induce osteogenic differentiation. For example, bone morphogenetic protein-9 (BMP9) has been found to have potent osteogenic activity. In the present study, PDLSCs were isolated from human periodontal membrane and infected with recombinant adenoviruses expressing BMP9 (Ad-BMP9). Levels of osteogenic markers such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) as well as mineralization ability were measured. The results showed that BMP9 promoted bone formation of PDLSCs. In other experiments, SB203580 and PD98059, which are inhibitors of p38 and ERK1/2, respectively, were used to determine if these kinases are involved in the osteogenic differentiation process. The resulting protein expression profiles and osteogenic markers of PDLSCs revealed that the mitogen-activated protein kinase (MAPK) signaling pathway might play an important role in the process of BMP9-induced osteogenic differentiation of PDLSCs. PMID- 25136264 TI - Age- and sex-specific spatio-temporal patterns of colorectal cancer mortality in Spain (1975-2008). AB - In this paper, space-time patterns of colorectal cancer (CRC) mortality risks are studied by sex and age group (50-69, >=70) in Spanish provinces during the period 1975-2008. Space-time conditional autoregressive models are used to perform the statistical analyses. A pronounced increase in mortality risk has been observed in males for both age-groups. For males between 50 and 69 years of age, trends seem to stabilize from 2001 onward. In females, trends reflect a more stable pattern during the period in both age groups. However, for the 50-69 years group, risks take an upward trend in the period 2006-2008 after the slight decline observed in the second half of the period. This study offers interesting information regarding CRC mortality distribution among different Spanish provinces that could be used to improve prevention policies and resource allocation in different regions. PMID- 25136262 TI - Astragaloside IV alleviates early brain injury following experimental subarachnoid hemorrhage in rats. AB - Astragaloside IV, one of the main effective components isolated from Astragalus membranaceus, has multiple neuroprotective properties, while the effects of astragaloside IV on the attenuation of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) and its possible mechanisms are unknown. In the present study, we aimed to determine whether astragaloside IV could inhibit oxidative stress, reduce neuronal apoptosis, and improve neurological deficits after experimental SAH in rats. Rats (n=68) were randomly divided into the following groups: Sham group, SAH group, SAH+vehicle group, and SAH+astragaloside IV group. Astragaloside IV or an equal volume of vehicle was administered at 1 h and 6 h after SAH, all the rats were subsequently sacrificed at 24 h after SAH. Mortality, neurological scores, and brain edema were assessed, biochemical tests and histological studies were also performed at that point. SAH induced an increase in the malondialdehyde (MDA) level, neuronal apoptosis, cleaved caspase 3, brain edema and decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Astragaloside IV treatment reversed these changes and improved neurobehavioral outcomes of SAH rats. Our findings suggested that astragaloside IV may alleviate EBI after SAH through antioxidative and anti apoptotic effects. PMID- 25136265 TI - Blau syndrome, the prototypic auto-inflammatory granulomatous disease. AB - Blau syndrome is a monogenic disease resulting from mutations in the pattern recognition receptor NOD2, and is phenotypically characterized by the triad of granulomatous polyarthritis, dermatitis and uveitis. This paper reviews briefly the classical clinical features of the disease, as well as more recently described extra-triad symptoms. From an ongoing prospective multicenter study, we provide new data on the natural history of Blau syndrome, focusing on functional status and visual outcome. We also present an update of the range of different NOD2 mutations found in Blau syndrome as well as recent data on morphologic and immunohistochemical characteristics of the Blau granuloma. Finally, emerging insights into pathogenic mechanisms including activation of NOD2 signal transduction, and potential biomarkers of disease activity are discussed. PMID- 25136266 TI - A Coarse-Grained Model of Unstructured Single-Stranded DNA Derived from Atomistic Simulation and Single-Molecule Experiment. AB - A simple coarse-grained model of single-stranded DNA (ssDNA) was developed, featuring only two sites per nucleotide that represent the centers of mass of the backbone and sugar/base groups. In the model, the interactions between sites are described using tabulated bonded potentials optimized to reproduce the solution structure of DNA observed in atomistic molecular dynamics simulations. Isotropic potentials describe nonbonded interactions, implicitly taking into account the solvent conditions to match the experimentally determined radius of gyration of ssDNA. The model reproduces experimentally measured force-extension dependence of an unstructured DNA strand across 2 orders of magnitude of the applied force. The accuracy of the model was confirmed by measuring the end-to-end distance of a dT14 fragment via FRET while stretching the molecules using optical tweezers. The model offers straightforward generalization to systems containing double-stranded DNA and DNA binding proteins. PMID- 25136268 TI - Computing the Free Energy Barriers for Less by Sampling with a Coarse Reference Potential while Retaining Accuracy of the Target Fine Model. AB - Proposed in this contribution is a protocol for calculating fine-physics (e.g., ab initio QM/MM) free-energy surfaces at a high level of accuracy locally (e.g., only at reactants and at the transition state for computing the activation barrier) from targeted fine-physics sampling and extensive exploratory coarse physics sampling. The full free-energy surface is still computed but at a lower level of accuracy from coarse-physics sampling. The method is analytically derived in terms of the umbrella sampling and the free-energy perturbation methods which are combined with the thermodynamic cycle and the targeted sampling strategy of the paradynamics approach. The algorithm starts by computing low accuracy fine-physics free-energy surfaces from the coarse-physics sampling in order to identify the reaction path and to select regions for targeted sampling. Thus, the algorithm does not rely on the coarse-physics minimum free-energy reaction path. Next, segments of high-accuracy free-energy surface are computed locally at selected regions from the targeted fine-physics sampling and are positioned relative to the coarse-physics free-energy shifts. The positioning is done by averaging the free-energy perturbations computed with multistep linear response approximation method. This method is analytically shown to provide results of the thermodynamic integration and the free-energy interpolation methods, while being extremely simple in implementation. Incorporating the metadynamics sampling to the algorithm is also briefly outlined. The application is demonstrated by calculating the B3LYP//6-31G*/MM free-energy barrier for an enzymatic reaction using a semiempirical PM6/MM reference potential. These modifications allow computing the activation free energies at a significantly reduced computational cost but at the same level of accuracy compared to computing full potential of mean force. PMID- 25136267 TI - Quantifying the Sources of Kinetic Frustration in Folding Simulations of Small Proteins. AB - Experiments and atomistic simulations of polypeptides have revealed structural intermediates that promote or inhibit conformational transitions to the native state during folding. We invoke a concept of "kinetic frustration" to quantify the prevalence and impact of these behaviors on folding rates within a large set of atomistic simulation data for 10 fast-folding proteins, where each protein's conformational space is represented as a Markov state model of conformational transitions. Our graph theoretic approach addresses what conformational features correlate with folding inhibition and therefore permits comparison among features within a single protein network and also more generally between proteins. Nonnative contacts and nonnative secondary structure formation can thus be quantitatively implicated in inhibiting folding for several of the tested peptides. PMID- 25136269 TI - Inferring Microscopic Kinetic Rates from Stationary State Distributions. AB - We present a principled approach for estimating the matrix of microscopic transition probabilities among states of a Markov process, given only its stationary state population distribution and a single average global kinetic observable. We adapt Maximum Caliber, a variational principle in which the path entropy is maximized over the distribution of all possible trajectories, subject to basic kinetic constraints and some average dynamical observables. We illustrate the method by computing the solvation dynamics of water molecules from molecular dynamics trajectories. PMID- 25136270 TI - Drug Resistance Mutations Alter Dynamics of Inhibitor-Bound HIV-1 Protease. AB - Under the selective pressure of therapy, HIV-1 protease mutants resistant to inhibitors evolve to confer drug resistance. Such mutations can impact both the dynamics and structures of the bound and unbound forms of the enzyme. Flap+ is a multidrug-resistant variant of HIV-1 protease with a combination of primary and secondary resistance mutations (L10I, G48V, I54V, V82A) and a strikingly altered thermodynamic profile for darunavir (DRV) binding relative to the wild-type protease. We elucidated the impact of these mutations on protein dynamics in the DRV-bound state using molecular dynamics simulations and NMR relaxation experiments. Both methods concur in that the conformational ensemble and dynamics of protease are impacted by the drug resistance mutations in Flap+ variant. Surprisingly this change in ensemble dynamics is different from that observed in the unliganded form of the same variant (Cai, Y. et al. J. Chem. Theory Comput.2012, 8, 3452-3462). Our comparative analysis of both inhibitor-free and bound states presents a comprehensive picture of the altered dynamics in drug resistant mutant HIV-1 protease and underlies the importance of incorporating dynamic analysis of the whole system, including the unliganded state, into revealing drug resistance mechanisms. PMID- 25136272 TI - Influence of Sequence and Covalent Modifications on Yeast tRNA Dynamics. AB - Modified nucleotides are prevalent in tRNA. Experimental studies reveal that these covalent modifications play an important role in tuning tRNA function. In this study, molecular dynamics (MD) simulations were used to investigate how modifications alter tRNA dynamics. The X-ray crystal structures of tRNA(Asp), tRNA(Phe), and tRNA(iMet), both with and without modifications, were used as initial structures for 333 ns explicit solvent MD simulations with AMBER. For each tRNA molecule, three independent trajectory calculations were performed, giving an aggregate of 6 MUs of total MD across six molecules. The global root mean-square deviations (RMSD) of atomic positions show that modifications only introduce significant rigidity to the global structure of tRNA(Phe). Interestingly, RMSDs of the anticodon stem-loop (ASL) suggest that modified tRNA has a more rigid structure compared to the unmodified tRNA in this domain. The anticodon RMSDs of the modified tRNAs, however, are higher than those of corresponding unmodified tRNAs. These findings suggest that the rigidity of the anticodon stem-loop is finely tuned by modifications, where rigidity in the anticodon arm is essential for tRNA translocation in the ribosome, and flexibility of the anticodon is important for codon recognition. Sugar pucker and water residence time of pseudouridines in modified tRNAs and corresponding uridines in unmodified tRNAs were assessed, and the results reinforce that pseudouridine favors the 3'-endo conformation and has a higher tendency to interact with water. Principal component analysis (PCA) was used to examine correlated motions in tRNA. Additionally, covariance overlaps of PCAs were compared for trajectories of the same molecule and between trajectories of modified and unmodified tRNAs. The comparison suggests that modifications alter the correlated motions. For the anticodon bases, the extent of stacking was compared between modified and unmodified molecules, and only unmodified tRNA(Asp) has significantly higher percentage of stacking time. Overall, the simulations reveal that the effect of covalent modification on tRNA dynamics is not simple, with modifications increasing flexibility in some regions of the structure and increasing rigidity in other regions. PMID- 25136273 TI - Conformational Transition Pathways of Epidermal Growth Factor Receptor Kinase Domain from Multiple Molecular Dynamics Simulations and Bayesian Clustering. AB - The epidermal growth factor receptor (EGFR) is aberrantly activated in various cancer cells and an important target for cancer treatment. Deep understanding of EGFR conformational changes between the active and inactive states is of pharmaceutical interest. Here we present a strategy combining multiply targeted molecular dynamics simulations, unbiased molecular dynamics simulations, and Bayesian clustering to investigate transition pathways during the activation/inactivation process of EGFR kinase domain. Two distinct pathways between the active and inactive forms are designed, explored, and compared. Based on Bayesian clustering and rough two-dimensional free energy surfaces, the energy favorable pathway is recognized, though DFG-flip happens in both pathways. In addition, another pathway with different intermediate states appears in our simulations. Comparison of distinct pathways also indicates that disruption of the Lys745-Glu762 interaction is critically important in DFG-flip while movement of the A-loop significantly facilitates the conformational change. Our simulations yield new insights into EGFR conformational transitions. Moreover, our results verify that this approach is valid and efficient in sampling of protein conformational changes and comparison of distinct pathways. PMID- 25136271 TI - Transferring the PRIMO Coarse-Grained Force Field to the Membrane Environment: Simulations of Membrane Proteins and Helix-Helix Association. AB - An extension of the recently developed PRIMO coarse-grained force field to membrane environments, PRIMO-M, is described. The membrane environment is modeled with the heterogeneous dielectric generalized Born (HDGB) methodology that simply replaces the standard generalized Born model in PRIMO without further parametrization. The resulting model was validated by comparing amino acid insertion free energy profiles and application in molecular dynamics simulations of membrane proteins and membrane-interacting peptides. Membrane proteins with 148-661 amino acids show stable root-mean-squared-deviations (RMSD) between 2 and 4 A for most systems. Transmembrane helical peptides maintain helical shape and exhibit tilt angles in good agreement with experimental or other simulation data. The association of two glycophorin A (GpA) helices was simulated using replica exchange molecular dynamics simulations yielding the correct dimer structure with a crossing angle in agreement with previous studies. Finally, conformational sampling of the influenza fusion peptide also generates structures in agreement with previous studies. Overall, these findings suggest that PRIMO-M can be used to study membrane bound peptides and proteins and validates the transferable nature of the PRIMO coarse-grained force field. PMID- 25136275 TI - Studies on the annealing and antibacterial properties of the silver-embedded aluminum/silica nanospheres. AB - Substantial silver-embedded aluminum/silica nanospheres with uniform diameter and morphology were successfully synthesized by sol-gel technique. After various annealing temperatures, the surface mechanisms of each sample were analyzed using scanning electron microscope, transmission electron microscope, and X-ray photoelectron spectroscopy. The chemical durability examinations and antibacterial tests of each sample were also carried out for the confirmation of its practical usage. Based on the result of the above analyses, the silver embedded aluminum/silica nanospheres are eligible for fabricating antibacterial utensils. PMID- 25136274 TI - Hamiltonian Switch Metropolis Monte Carlo Simulations for Improved Conformational Sampling of Intrinsically Disordered Regions Tethered to Ordered Domains of Proteins. AB - There is growing interest in the topic of intrinsically disordered proteins (IDPs). Atomistic Metropolis Monte Carlo (MMC) simulations based on novel implicit solvation models have yielded useful insights regarding sequence ensemble relationships for IDPs modeled as autonomous units. However, a majority of naturally occurring IDPs are tethered to ordered domains. Tethering introduces additional energy scales and this creates the challenge of broken ergodicity for standard MMC sampling or molecular dynamics that cannot be readily alleviated by using generalized tempering methods. We have designed, deployed, and tested our adaptation of the Nested Markov Chain Monte Carlo sampling algorithm. We refer to our adaptation as Hamiltonian Switch Metropolis Monte Carlo (HS-MMC) sampling. In this method, transitions out of energetic traps are enabled by the introduction of an auxiliary Markov chain that draws conformations for the disordered region from a Boltzmann distribution that is governed by an alternative potential function that only includes short-range steric repulsions and conformational restraints on the ordered domain. We show using multiple, independent runs that the HS-MMC method yields conformational distributions that have similar and reproducible statistical properties, which is in direct contrast to standard MMC for equivalent amounts of sampling. The method is efficient and can be deployed for simulations of a range of biologically relevant disordered regions that are tethered to ordered domains. PMID- 25136277 TI - Tuning of strain and surface roughness of porous silicon layers for higher quality seeds for epitaxial growth. AB - Sintered porous silicon is a well-known seed for homo-epitaxy that enables fabricating transferrable monocrystalline foils. The crystalline quality of these foils depends on the surface roughness and the strain of this porous seed, which should both be minimized. In order to provide guidelines for an optimum foil growth, we present a systematic investigation of the impact of the thickness of this seed and of its sintering time prior to epitaxial growth on strain and surface roughness. Strain and surface roughness were monitored in monolayers and double layers with different porosities as a function of seed thickness and of sintering time by high-resolution X-ray diffraction and profilometry, respectively. Unexpectedly, we found that strain in double and monolayers evolves in opposite ways with respect to layer thickness. This suggests that an interaction between layers in multiple stacks is to be considered. We also found that if higher seed thickness and longer annealing time are to be preferred to minimize the strain in double layers, the opposite is required to achieve smoother layers. The impact of these two parameters may be explained by considering the morphological evolution of the pores upon sintering and, in particular, the disappearance of interconnections between the porous seed and the bulk as well as the enlargement of pores near the surface. An optimum epitaxial growth hence calls for a trade-off in seed thickness and annealing time, between minimum-strained layers and rougher surfaces. PACS CODES: 81.40.-z Treatment of materials and its effects on microstructure, nanostructure, and properties; 81.05.Rm Porous materials; granular materials; 82.80.Ej X-ray, Mossbauer and other gamma-ray spectroscopic analysis methods. PMID- 25136276 TI - Fabrication of low-density GaN/AlN quantum dots via GaN thermal decomposition in MOCVD. AB - With an appropriate high anneal temperature under H2 atmosphere, GaN quantum dots (QDs) have been fabricated via GaN thermal decomposition in metal organic chemical vapor deposition (MOCVD). Based on the characterization of atomic force microscopy (AFM), the obtained GaN QDs show good size distribution and have a low density of 2.4 * 10(8) cm(-2). X-ray photoelectron spectroscopy (XPS) analysis demonstrates that the GaN QDs were formed without Ga droplets by thermal decomposition of GaN. PMID- 25136278 TI - Tuning the peak position of subwavelength silica nanosphere broadband antireflection coatings. AB - Subwavelength nanostructures are considered as promising building blocks for antireflection and light trapping applications. In this study, we demonstrate excellent broadband antireflection effect from thin films of monolayer silica nanospheres with a diameter of 100 nm prepared by Langmuir-Blodgett method on glass substrates. With a single layer of compact silica nanosphere thin film coated on both sides of a glass, we achieved maximum transmittance of 99% at 560 nm. Furthermore, the optical transmission peak of the nanosphere thin films can be tuned over the UV-visible range by changing processing parameters during Langmuir-Blodgett deposition. The tunable optical transmission peaks of the Langmuir-Blodgett films were correlated with deposition parameters such as surface pressure, surfactant concentration, ageing of suspensions and annealing effect. Such peak-tunable broadband antireflection coating has wide applications in diversified industries such as solar cells, windows, displays and lenses. PMID- 25136280 TI - Controllable preparation of Ni nanoparticles for catalysis of coiled carbon fibers growth. AB - The mass preparation of high-purity coiled carbon fibers (CCFs) remains challenging due to the high complexity and low controllability of reaction. In this work, a controllable growth of Ni particles was fulfilled by liquid phase reduction of nickel sulfate with hydrazine hydrate. The impacts of the reaction temperature, NaOH concentration, and reaction time on the particle size and purity were investigated. The as-deposited Ni particles were characterized by scanning electron microscopy and X-ray diffraction. In addition, these Ni particles were also applied in preparing high-purity CCFs both on graphite and ceramic substrates. The diameter of the as-grown carbon microcoil was about 500 nm, and the related growth mechanism was discussed. PMID- 25136279 TI - Copper pillar and memory characteristics using Al2O3 switching material for 3D architecture. AB - A novel idea by using copper (Cu) pillar is proposed in this study, which can replace the through-silicon-vias (TSV) technique in future three-dimensional (3D) architecture. The Cu pillar formation under external bias in an Al/Cu/Al2O3/TiN structure is simple and low cost. The Cu pillar is formed in the Al2O3 film under a small operation voltage of <5 V and a high-current-carrying conductor of >70 mA is obtained. More than 100 devices have shown tight distribution of the Cu pillars in Al2O3 film for high current compliance (CC) of 70 mA. Robust read pulse endurances of >10(6) cycles are observed with read voltages of -1, 1, and 4 V. However, read endurance is failed with read voltages of -1.5, -2, and -4 V. By decreasing negative read voltage, the read endurance is getting worst, which is owing to ruptured Cu pillar. Surface roughness and TiO x N y on TiN bottom electrode are observed by atomic force microscope and transmission electron microscope, respectively. The Al/Cu/Al2O3/TiN memory device shows good bipolar resistive switching behavior at a CC of 500 MUA under small operating voltage of +/-1 V and good data retention characteristics of >10(3) s with acceptable resistance ratio of >10 is also obtained. This suggests that high-current operation will help to form Cu pillar and lower-current operation will have bipolar resistive switching memory. Therefore, this new Cu/Al2O3/TiN structure will be benefited for 3D architecture in the future. PMID- 25136281 TI - Enhanced antibacterial and anti-biofilm activities of silver nanoparticles against Gram-negative and Gram-positive bacteria. AB - Silver nanoparticles (AgNPs) have been used as antibacterial, antifungal, antiviral, anti-inflammtory, and antiangiogenic due to its unique properties such as physical, chemical, and biological properties. The present study was aimed to investigate antibacterial and anti-biofilm activities of silver nanoparticles alone and in combination with conventional antibiotics against various human pathogenic bacteria. Here, we show that a simple, reliable, cost effective and green method for the synthesis of AgNPs by treating silver ions with leaf extract of Allophylus cobbe. The A. cobbe-mediated synthesis of AgNPs (AgNPs) was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Furthermore, the antibacterial and anti-biofilm activity of antibiotics or AgNPs, or combinations of AgNPs with an antibiotic was evaluated using a series of assays: such as in vitro killing assay, disc diffusion assay, biofilm inhibition, and reactive oxygen species generation in Pseudomonas aeruginosa, Shigella flexneri, Staphylococcus aureus, and Streptococcus pneumonia. The results suggest that, in combination with antibiotics, there were significant antimicrobial and anti-biofilm effects at lowest concentration of AgNPs using a novel plant extract of A. cobbe, otherwise sublethal concentrations of the antibiotics. The significant enhancing effects were observed for ampicillin and vancomycin against Gram-negative and Gram-positive bacteria, respectively. These data suggest that combining antibiotics and biogenic AgNPs can be used therapeutically for the treatment of infectious diseases caused by bacteria. This study presented evidence of antibacterial and anti-biofilm effects of A. cobbe-mediated synthesis of AgNPs and their enhanced capacity against various human pathogenic bacteria. These results suggest that AgNPs could be used as an adjuvant for the treatment of infectious diseases. PMID- 25136282 TI - Pyrolysis and co-pyrolysis of Laminaria japonica and polypropylene over mesoporous Al-SBA-15 catalyst. AB - The catalytic co-pyrolysis of a seaweed biomass, Laminaria japonica, and a typical polymer material, polypropylene, was studied for the first time. A mesoporous material Al-SBA-15 was used as a catalyst. Pyrolysis experiments were conducted using a fixed-bed reactor and pyrolysis gas chromatography/mass spectrometry (Py-GC/MS). BET surface area, N2 adsorption-desorption isotherms, and NH3 temperature programmed desorption were measured to examine the catalyst characteristics. When only L. japonica was pyrolyzed, catalytic reforming slightly increased the gas yield and decreased the oil yield. The H2O content in bio-oil was increased by catalytic reforming from 42.03 to 50.32 wt% due to the dehydration reaction occurring on the acid sites inside the large pores of Al-SBA 15. Acids, oxygenates, mono-aromatics, poly aromatic hydrocarbons, and phenolics were the main components of the bio-oil obtained from the pyrolysis of L. japonica. Upon catalytic reforming over Al-SBA-15, the main oxygenate species 1,4 anhydro-d-galactitol and 1,5-anhydro-d-manitol were completely removed. When L. japonica was co-pyrolyzed with polypropylene, the H2O content in bio-oil was decreased dramatically (8.93 wt% in the case of catalytic co-pyrolysis), contributing to the improvement of the oil quality. A huge increase in the content of gasoline-range and diesel-range hydrocarbons in bio-oil was the most remarkable change that resulted from the co-pyrolysis with polypropylene, suggesting its potential as a transport fuel. The content of mono-aromatics with high economic value was also increased significantly by catalytic co-pyrolysis. PMID- 25136283 TI - Controlled growth of 1D and 2D ZnO nanostructures on 4H-SiC using Au catalyst. AB - A perfect control of nanostructure growth is a prerequisite for the development of electronic and optoelectronic device/systems. In this article, we demonstrate the growth of various ZnO-derived nanostructures, including well-ordered arrays of high aspect ratio single crystalline nanowires with preferred growth direction along the [0001] axis, nanowalls, and hybrid nanowire-nanowall structures. The growths of the various ZnO nanostructures have been carried out on SiC substrates in a horizontal furnace, using Au thin film as catalyst. From experimental observations, we have ascribed the growth mechanisms of the different ZnO nanostructures to be a combination of catalytic-assisted and non-catalytic assisted vapor-liquid-solid (VLS) processes. We have also found that the different ZnO nanoarchitectures' material evolution is governed by a Zn cluster drift effects on the SiC surface mainly driven by growth temperature. Au thin film thickness, growth time, and temperature are the parameters to optimize in order to obtain the different ZnO nanoarchitectures. PMID- 25136284 TI - Improving the performance of dye-sensitized solar cells with TiO2/graphene/TiO2 sandwich structure. AB - This study investigates the extent to which the TiO2/graphene/TiO2 sandwich structure improves the performance of dye-sensitized solar cells (DSSCs) over that of DSSCs with the traditional structure. Studies have demonstrated that the TiO2/graphene/TiO2 sandwich structure effectively enhances the open circuit voltage (V oc), short-circuit current density (J sc), and photoelectrical conversion efficiency (eta) of DSSCs. The enhanced performance of DSSCs with the sandwich structure can be attributed to an increase in electron transport efficiency and in the absorption of light in the visible range. The DSSC with the sandwich structure in this study exhibited a V oc of 0.6 V, a high J sc of 11.22 mA cm(-2), a fill factor (FF) of 0.58, and a calculated eta of 3.93%, which is 60% higher than that of a DSSC with the traditional structure. PMID- 25136285 TI - Porous silicon Bloch surface and sub-surface wave structure for simultaneous detection of small and large molecules. AB - A porous silicon (PSi) Bloch surface wave (BSW) and Bloch sub-surface wave (BSSW) composite biosensor is designed and used for the size-selective detection of both small and large molecules. The BSW/BSSW structure consists of a periodic stack of high and low refractive index PSi layers and a reduced optical thickness surface layer that gives rise to a BSW with an evanescent tail that extends above the surface to enable the detection of large surface-bound molecules. Small molecules were detected in the sensor by the BSSW, which is a large electric field intensity spatially localized to a desired region of the Bragg mirror and is generated by the implementation of a step or gradient refractive index profile within the Bragg mirror. The step and gradient BSW/BSSW sensors are designed to maximize both resonance reflectance intensity and sensitivity to large molecules. Size-selective detection of large molecules including latex nanospheres and the M13KO7 bacteriophage as well as small chemical linker molecules is reported. PMID- 25136286 TI - Superhydrophobic ZnO networks with high water adhesion. AB - ZnO structures were deposited using a simple chemical bath deposition technique onto interdigitated electrodes fabricated by a conventional photolithography method on SiO2/Si substrates. The X-ray diffraction studies show that the ZnO samples have a hexagonal wurtzite crystalline structure. The scanning electron microscopy observations prove that the substrates are uniformly covered by ZnO networks formed by monodisperse rods. The ZnO rod average diameter and length were tuned by controlling reactants' concentration and reaction time. Optical spectroscopy measurements demonstrate that all the samples display bandgap values and emission bands typical for ZnO. The electrical measurements reveal percolating networks which are highly sensitive when the samples are exposed to ammonia vapors, a variation in their resistance with the exposure time being evidenced. Other important characteristics are that the ZnO rod networks exhibit superhydrophobicity, with water contact angles exceeding 150 degrees and a high water droplet adhesion. Reproducible, easily scalable, and low-cost chemical bath deposition and photolithography techniques could provide a facile approach to fabricate such ZnO networks and devices based on them for a wide range of applications where multifunctionality, i.e., sensing and superhydrophobicity, properties are required. PACS: 81.07.-b; 81.05.Dz; 68.08.Bc. PMID- 25136287 TI - Photocurrent enhancement mechanisms in bilayer nanofilm-based ultraviolet photodetectors made from ZnO and ZnS spherical nanoshells. AB - Hollow-sphere bilayer nanofilm-based ultraviolet light photodetectors made from ZnO and ZnS spherical nanoshells show enhanced photocurrent, which are comparable to or even better than those of other semiconductor nanostructures with different shapes. In this work, the photocurrent enhancement mechanisms of these bilayer nanofilm-based ultraviolet light photodetectors are explained, which could be attributed to the strong light absorption based on the whispering gallery mode resonances, the separation of the photogenerated carriers through the internal electric field within the bilayer nanofilms, the hopping-like electrical transport, and the effective charge injection from Cr/Au contacts to the nanofilms. PMID- 25136289 TI - Removal of Cr(VI) from Aqueous Solutions Using Powder of Potato Peelings as a Low Cost Sorbent. AB - Potato peels which are a low cost, renewable agroindustry by-product were used for the removal of hexavalent chromium from aqueous effluents. Batch experiments were carried out with an artificial effluent comprising of potassium dichromate in deionised water. The effects of the initial hexavalent chromium concentration, dose of biosorbent, and removal kinetics were explored. An adsorbent dosage of 4 g/L was effective in complete removal of the metal ion, at pH 2.5, in 48 minutes. The kinetic process of Cr(VI) adsorption onto potato peel powder was tested by applying pseudo-first-order and pseudo-second-order models as well as the Elovich kinetic equation to correlate the experimental data and to determine the kinetic parameters. The adsorption data were correlated by the Langmuir and Freundlich isotherms. A maximum monolayer adsorption capacity of 3.28 mg/g was calculated using the Langmuir adsorption isotherm, suggesting a functional group limited adsorption process. The results confirmed that potato peels are an effective biosorbent for the removal of hexavalent chromium from effluent. PMID- 25136288 TI - Proteomic profile of pre - B2 lymphoblasts from children with acute lymphoblastic leukemia (ALL) in relation with the translocation (12; 21). AB - BACKGROUND: Until now, the major prognostic factors for pediatric acute lymphoblastic leukemia (ALL), age, white blood cell count and chromosomal alterations are initially taken into account for the risk stratification of patients. In the light of protein marker studies to classify subtypes of Acute Myeloblastic Leukemia efficiently, we have compared the lymphoblastes proteome in Childhood ALL in accordance with the presence of t(12;21), indicator of good prognosis, usually. METHODS: Protein expression in pre-B2 lymphoblastic cells, collected from residual bone marrow cells after diagnostic procedures, was analyzed using two dimensional gel electrophoresis protocol. Protein spots whose average normalized volumes were statistically different in the two patients groups (n = 13; student t test p < 0.01), were excised. Tryptic peptides were then analyzed using a nano-LC1200 system coupled to a 6340 Ion Trap mass spectrometer equipped with a HPLC-chip cube interface. The tandem mass spectrometry peak lists extracted using the DataAnalysis program, were compared with the protein database Mascot Daemon. RESULTS: We focused on twelve spots corresponding to sixteen identified candidate proteins among the 26 found differentially expressed (p <= 0.05) regarding the presence of t(12;21). Among over expressed proteins, two proteins were implicated in cellular growth arrest (i.e. calponine 2, p <= 0.001 and phosphatidylinositol transfer protein beta, p <= 0.001) in accordance with good prognosis, while two other proteins favored cell cycle proliferation (i.e. methionine adenosyl transferase 2beta, p <= 0.005 and heterogeneous nuclear ribonucleo-proteins A2 p <= 0.01) and could therefore be good marker candidates of aggressiveness. Level of expression of proteasome subunit beta type-2 (p <= 0.01) and protein casein kinase 2alpha (p <= 0.01) which both favored apoptosis, deubiquitinating enzyme OTUB1 (p <= 0.05) and MLL septin-like fusion protein MSF-B, septin 9 i4 (p <= 0.01) were in accord with a good prognosis related to t(12;21) lymphoblasts. CONCLUSION: By drawing up the protein map of leukemic cells, these new data identified marker candidates of leukemic aggressiveness and new t(12;21) patients subgroups. These preliminary results will be in the near future confirmed by using a larger sample of pre-B2 childhood ALLs from national lymphoblastic cell collections. PMID- 25136290 TI - Single trial prediction of self-paced reaching directions from EEG signals. AB - Early detection of movement intention could possibly minimize the delays in the activation of neuroprosthetic devices. As yet, single trial analysis using non invasive approaches for understanding such movement preparation remains a challenging task. We studied the feasibility of predicting movement directions in self-paced upper limb center-out reaching tasks, i.e., spontaneous movements executed without an external cue that can better reflect natural motor behavior in humans. We reported results of non-invasive electroencephalography (EEG) recorded from mild stroke patients and able-bodied participants. Previous studies have shown that low frequency EEG oscillations are modulated by the intent to move and therefore, can be decoded prior to the movement execution. Motivated by these results, we investigated whether slow cortical potentials (SCPs) preceding movement onset can be used to classify reaching directions and evaluated the performance using 5-fold cross-validation. For able-bodied subjects, we obtained an average decoding accuracy of 76% (chance level of 25%) at 62.5 ms before onset using the amplitude of on-going SCPs with above chance level performances between 875 to 437.5 ms prior to onset. The decoding accuracy for the stroke patients was on average 47% with their paretic arms. Comparison of the decoding accuracy across different frequency ranges (i.e., SCPs, delta, theta, alpha, and gamma) yielded the best accuracy using SCPs filtered between 0.1 to 1 Hz. Across all the subjects, including stroke subjects, the best selected features were obtained mostly from the fronto-parietal regions, hence consistent with previous neurophysiological studies on arm reaching tasks. In summary, we concluded that SCPs allow the possibility of single trial decoding of reaching directions at least 312.5 ms before onset of reach. PMID- 25136292 TI - The desferrioxamine-prochlorperazine coma-clue to the role of dopamine-iron recycling in the synthesis of hydrogen peroxide in the brain. PMID- 25136293 TI - Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and are regulated in brain in an acute model of inflammation. AB - A family of endogenous lipids, structurally analogous to the endogenous cannabinoid, N-arachidonoyl ethanolamine (Anandamide), and called N-acyl amides have emerged as a family of biologically active compounds at TRP receptors. N acyl amides are constructed from an acyl group and an amine via an amide bond. This same structure can be modified by changing either the fatty acid or the amide to form potentially hundreds of lipids. More than 70 N-acyl amides have been identified in nature. We have ongoing studies aimed at isolating and characterizing additional members of the family of N-acyl amides in both central and peripheral tissues in mammalian systems. Here, using a unique in-house library of over 70 N-acyl amides we tested the following three hypotheses: (1) Additional N-acyl amides will have activity at TRPV1-4, (2) Acute peripheral injury will drive changes in CNS levels of N-acyl amides, and (3) N-acyl amides will regulate calcium in CNS-derived microglia. Through these studies, we have identified 20 novel N-acyl amides that collectively activate (stimulating or inhibiting) TRPV1-4. Using lipid extraction and HPLC coupled to tandem mass spectrometry we showed that levels of at least 10 of these N-acyl amides that activate TRPVs are regulated in brain after intraplantar carrageenan injection. We then screened the BV2 microglial cell line for activity with this N-acyl amide library and found overlap with TRPV receptor activity as well as additional activators of calcium mobilization from these lipids. Together these data provide new insight into the family of N-acyl amides and their roles as signaling molecules at ion channels, in microglia, and in the brain in the context of inflammation. PMID- 25136291 TI - How may the basal ganglia contribute to auditory categorization and speech perception? AB - Listeners must accomplish two complementary perceptual feats in extracting a message from speech. They must discriminate linguistically-relevant acoustic variability and generalize across irrelevant variability. Said another way, they must categorize speech. Since the mapping of acoustic variability is language specific, these categories must be learned from experience. Thus, understanding how, in general, the auditory system acquires and represents categories can inform us about the toolbox of mechanisms available to speech perception. This perspective invites consideration of findings from cognitive neuroscience literatures outside of the speech domain as a means of constraining models of speech perception. Although neurobiological models of speech perception have mainly focused on cerebral cortex, research outside the speech domain is consistent with the possibility of significant subcortical contributions in category learning. Here, we review the functional role of one such structure, the basal ganglia. We examine research from animal electrophysiology, human neuroimaging, and behavior to consider characteristics of basal ganglia processing that may be advantageous for speech category learning. We also present emerging evidence for a direct role for basal ganglia in learning auditory categories in a complex, naturalistic task intended to model the incidental manner in which speech categories are acquired. To conclude, we highlight new research questions that arise in incorporating the broader neuroscience research literature in modeling speech perception, and suggest how understanding contributions of the basal ganglia can inform attempts to optimize training protocols for learning non-native speech categories in adulthood. PMID- 25136295 TI - Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome activation and cell death in astroglial cells. AB - Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are innate immunity sensors that provide an early/effective response to pathogenic or injury conditions. We have reported that ethanol-induced TLR4 activation triggers signaling inflammatory responses in glial cells, causing neuroinflammation and brain damage. However, it is uncertain if ethanol is able to activate NLRs/inflammasome in astroglial cells, which is the mechanism of activation, and whether there is crosstalk between both immune sensors in glial cells. Here we show that chronic ethanol treatment increases the co-localization of caspase-1 with GFAP(+) cells, and up-regulates IL-1beta and IL-18 in the frontal medial cortex in WT, but not in TLR4 knockout mice. We further show that cultured cortical astrocytes expressed several inflammasomes (NLRP3, AIM2, NLRP1, and IPAF), although NLRP3 mRNA is the predominant form. Ethanol, as ATP and LPS treatments, up-regulates NLRP3 expression, and causes caspase-1 cleavage and the release of IL-1beta and IL-18 in astrocytes supernatant. Ethanol-induced NLRP3/caspase-1 activation is mediated by mitochondrial (m) reactive oxygen species (ROS) generation because when using a specific mitochondria ROS scavenger, the mito-TEMPO (500 MUM) or NLRP3 blocking peptide (4 MUg/ml) or a specific caspase-1 inhibitor, Z-YVAD-FMK (10 MUM), abrogates mROS release and reduces the up-regulation of IL-1beta and IL-18 induced by ethanol or LPS or ATP. Confocal microscopy studies further confirm that ethanol, ATP or LPS promotes NLRP3/caspase-1 complex recruitment within the mitochondria to promote cell death by caspase-1-mediated pyroptosis, which accounts for ~73% of total cell death (~22%) and the remaining (~25%) die by caspase-3-dependent apoptosis. Suppression of the TLR4 function abrogates most ethanol effects on NLRP3 activation and reduces cell death. These findings suggest that NLRP3 participates, in ethanol induced neuroinflammation and highlight the NLRP3/TLR4 crosstalk in ethanol induced brain injury. PMID- 25136296 TI - Computational modeling of the effects of auditory nerve dysmyelination. AB - Our previous study showed that exposure to loud sound leading to hearing loss elongated the auditory nerve (AN) nodes of Ranvier and triggered notable morphological changes at paranodes and juxtaparanodes. Here we used computational modeling to examine how theoretical redistribution of voltage gated Na(+), Kv3.1, and Kv1.1 channels along the AN may be responsible for the alterations of conduction property following acoustic over-exposure. Our modeling study infers that changes related to Na(+) channel density (rather than the redistribution of voltage gated Na(+), Kv3.1, and Kv1.1 channels) is the likely cause of the decreased conduction velocity and the conduction block observed after acoustic overexposure (AOE). PMID- 25136294 TI - Astrocytic modulation of blood brain barrier: perspectives on Parkinson's disease. AB - The blood-brain barrier (BBB) is a tightly regulated interface in the Central Nervous System (CNS) that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson's Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the ECs and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson's disease (PD) and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions. PMID- 25136298 TI - Modulation of social behavior by the agouti pigmentation gene. AB - Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors. Mice and rats lacking agouti (called non-agouti) have dark fur due to a disinhibition of melanocortin signaling and pigment deposition in the hair follicle. Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin. Here we confirm that non-agouti mice show altered social behavior and uncover expression of agouti in the preputial gland, a sebaceous organ in the urinary tract that secretes molecules involved in social behavior. Non-agouti mice had enlarged preputial glands and altered levels of putative preputial pheromones and surgical removal of the gland reversed the behavioral phenotype. These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior. PMID- 25136299 TI - Topographical disorientation after ischemic mini infarct in the dorsal hippocampus: whispers in silence. AB - Silent focal ischemic mini infarcts in the brain are thought to cause no clinically overt symptoms. Some populations of hippocampal cells are particularly sensitive to ischemic events, however, rendering hippocampal functions especially vulnerable to ischemia-induced deficits. The present study investigated whether an otherwise silent ischemic mini infarct in the hippocampus (HPC) can produce impairments in spatial performance in rats. Spatial performance was assessed in the ziggurat task (ZT) using a 10-trial spatial learning protocol for 4 days prior to undergoing hippocampal ischemic lesion or sham surgery. Hippocampal silent ischemia was induced by infusion of endothelin-1 (ET-1), a potent vasoconstrictor, into either the dorsal or the ventral hippocampus (dHPC and vHPC). When tested postoperatively in the ZT using a standard testing protocol for 8 days, rats with hippocampal lesions exhibited no spatial deficit. Although spatial learning and memory in the ZT were not affected by the ET-1-induced silent ischemia, rats with dHPC stroke showed more returns when navigating the ZT as opposed to the vHPC rats. Comparison of region-specific HPC lesions in the present study indicated that dorsal hippocampal function is critically required for topographic orientation in a complex environment. Topographic disorientation as reflected by enhanced return behaviors may represent one of the earliest predictors of cognitive decline after silent ischemic insult that may be potentially traced with sensitive clinical examination in humans. PMID- 25136301 TI - Beyond pain: modeling decision-making deficits in chronic pain. AB - Risky decision-making seems to be markedly disrupted in patients with chronic pain, probably due to the high cost that impose pain and negative mood on executive control functions. Patients' behavioral performance on decision-making tasks such as the Iowa Gambling Task (IGT) is characterized by selecting cards more frequently from disadvantageous than from advantageous decks, and by switching often between competing responses in comparison with healthy controls (HCs). In the present study, we developed a simple heuristic model to simulate individuals' choice behavior by varying the level of decision randomness and the importance given to gains and losses. The findings revealed that the model was able to differentiate the behavioral performance of patients with chronic pain and HCs at the group, as well as at the individual level. The best fit of the model in patients with chronic pain was yielded when decisions were not based on previous choices and when gains were considered more relevant than losses. By contrast, the best account of the available data in HCs was obtained when decisions were based on previous experiences and losses loomed larger than gains. In conclusion, our model seems to provide useful information to measure each individual participant extensively, and to deal with the data on a participant-by participant basis. PMID- 25136300 TI - Executive function and endocrinological responses to acute resistance exercise. AB - THIS STUDY HAD THE FOLLOWING TWO AIMS: First, to explore the effects of acute resistance exercise (RE, i.e., using exercise machines to contract and stretch muscles) on behavioral and electrophysiological performance when performing a cognitive task involving executive functioning in young male adults; Second, to investigate the potential biochemical mechanisms of such facilitative effects using two neurotrophic factors [i.e., growth hormone (GH) and insulin-like growth factor-1 (IGF-1)] and the cortisol levels elicited by such an exercise intervention mode with two different exercise intensities. Sixty young male adults were recruited and randomly assigned to a high-intensity (HI) exercise group, moderate-intensity (MI) exercise group, and non-exercise-intervention (NEI) group. Blood samples were taken, and the behavioral and electrophysiological indices were simultaneously measured when individuals performed a Go/No-Go task combined with the Erikson Flanker paradigm at baseline and after either an acute bout of 30 min of moderate- or high-intensity RE or a control period. The results showed that the acute RE could not only benefit the subjects' behavioral (i.e., RTs and accuracy) performance, as found in previous studies, but also increase the P3 amplitude. Although the serum GH and IGF-1 levels were significantly increased via moderate or high intensity RE in both the MI and HI groups, the increased serum levels of neurotrophic factors were significantly decreased about 20 min after exercise. In addition, such changes were not correlated with the changes in cognitive (i.e., behavioral and electrophysiological) performance. In contrast, the serum levels of cortisol in the HI and MI groups were significantly lower after acute RE, and the changes in cortisol levels were significantly associated with the changes in electrophysiological (i.e., P3 amplitude) performance. The findings suggest the beneficial effects of acute RE on executive functioning could be due to changes in arousal, possibly modulated by the serum cortisol levels. PMID- 25136297 TI - Unraveling the complexities of circadian and sleep interactions with memory formation through invertebrate research. AB - Across phylogeny, the endogenous biological clock has been recognized as providing adaptive advantages to organisms through coordination of physiological and behavioral processes. Recent research has emphasized the role of circadian modulation of memory in generating peaks and troughs in cognitive performance. The circadian clock along with homeostatic processes also regulates sleep, which itself impacts the formation and consolidation of memory. Thus, the circadian clock, sleep and memory form a triad with ongoing dynamic interactions. With technological advances and the development of a global 24/7 society, understanding the mechanisms underlying these connections becomes pivotal for development of therapeutic treatments for memory disorders and to address issues in cognitive performance arising from non-traditional work schedules. Invertebrate models, such as Drosophila melanogaster and the mollusks Aplysia and Lymnaea, have proven invaluable tools for identification of highly conserved molecular processes in memory. Recent research from invertebrate systems has outlined the influence of sleep and the circadian clock upon synaptic plasticity. In this review, we discuss the effects of the circadian clock and sleep on memory formation in invertebrates drawing attention to the potential of in vivo and in vitro approaches that harness the power of simple invertebrate systems to correlate individual cellular processes with complex behaviors. In conclusion, this review highlights how studies in invertebrates with relatively simple nervous systems can provide mechanistic insights into corresponding behaviors in higher organisms and can be used to outline possible therapeutic options to guide further targeted inquiry. PMID- 25136302 TI - Reduced resting-state functional connectivity of the somatosensory cortex predicts psychopathological symptoms in women with bulimia nervosa. AB - BACKGROUND: Alterations in the resting-state functional connectivity (rs-FC) of several brain networks have been demonstrated in eating disorders. However, very few studies are currently available on brain network dysfunctions in bulimia nervosa (BN). The somatosensory network is central in processing body-related stimuli and it may be altered in BN. The present study therefore aimed to investigate rs-FC in the somatosensory network in bulimic women. METHODS: Sixteen medication-free women with BN (age = 23 +/- 5 years) and 18 matched controls (age = 23 +/- 3 years) underwent a functional magnetic resonance resting-state scan and assessment of eating disorder symptoms. Within-network and seed-based functional connectivity analyses were conducted to assess rs-FC within the somatosensory network and to other areas of the brain. RESULTS: Bulimia nervosa patients showed a decreased rs-FC both within the somatosensory network (t = 9.0, df = 1, P = 0.005) and with posterior cingulate cortex and two visual areas (the right middle occipital gyrus and the right cuneus) (P = 0.05 corrected for multiple comparison). The rs-FC of the left paracentral lobule with the right middle occipital gyrus correlated with psychopathology measures like bulimia (r = -0.4; P = 0.02) and interoceptive awareness (r = -0.4; P = 0.01). Analyses were conducted using age, BMI (body mass index), and depressive symptoms as covariates. CONCLUSION: Our findings show a specific alteration of the rs-FC of the somatosensory cortex in BN patients, which correlates with eating disorder symptoms. The region in the right middle occipital gyrus is implicated in body processing and is known as extrastriate body area (EBA). The connectivity between the somatosensory cortex and the EBA might be related to dysfunctions in body image processing. The results should be considered preliminary due to the small sample size. PMID- 25136303 TI - Implicit sequence learning in people with Parkinson's disease. AB - Implicit sequence learning involves learning about dependencies in sequences of events without intent to learn or awareness of what has been learned. Sequence learning is related to striatal dopamine levels, striatal activation, and integrity of white matter connections. People with Parkinson's disease (PD) have degeneration of dopamine-producing neurons, leading to dopamine deficiency and therefore striatal deficits, and they have difficulties with sequencing, including complex language comprehension and postural stability. Most research on implicit sequence learning in PD has used motor-based tasks. However, because PD presents with motor deficits, it is difficult to assess whether learning itself is impaired in these tasks. The present study used an implicit sequence learning task with a reduced motor component, the Triplets Learning Task (TLT). People with PD and age- and education-matched healthy older adults completed three sessions (each consisting of 10 blocks of 50 trials) of the TLT. Results revealed that the PD group was able to learn the sequence, however, when learning was examined using a Half Blocks analysis (Nemeth et al., 2013), which compared learning in the 1st 25/50 trials of all blocks to that in the 2nd 25/50 trials, the PD group showed significantly less learning than Controls in the 2nd Half Blocks, but not in the 1st. Nemeth et al. (2013) hypothesized that the 1st Half Blocks involve recall and reactivation of the sequence learned, thus reflecting hippocampal-dependent learning, while the 2nd Half Blocks involve proceduralized behavior of learned sequences, reflecting striatal-based learning. The present results suggest that the PD group had intact hippocampal-dependent implicit sequence learning, but impaired striatal-dependent learning. Thus, sequencing deficits in PD are likely due to striatal impairments, but other brain systems, such as the hippocampus, may be able to partially compensate for striatal decline to improve performance. PMID- 25136304 TI - Digit forces bias sensorimotor transformations underlying control of fingertip position. AB - Humans are able to modulate digit forces as a function of position despite changes in digit placement that might occur from trial to trial or when changing grip type for object manipulation. Although this phenomenon is likely to rely on sensing the position of the digits relative to each other and the object, the underlying mechanisms remain unclear. To address this question, we asked subjects (n = 30) to match perceived vertical distance between the center of pressure (CoP) of the thumb and index finger pads (dy ) of the right hand ("reference" hand) using the same hand ("test" hand). The digits of reference hand were passively placed collinearly (dy = 0 mm). Subjects were then asked to exert different combinations of normal and tangential digit forces (Fn and Ftan , respectively) using the reference hand and then match the memorized dy using the test hand. The reference hand exerted Ftan of thumb and index finger in either same or opposite direction. We hypothesized that, when the tangential forces of the digits are produced in opposite directions, matching error (1) would be biased toward the directions of the tangential forces; and (2) would be greater when the remembered relative contact points are matched with negligible digit force production. For the test hand, digit forces were either negligible (0.5-1 N, 0 +/- 0.25 N; Experiment 1) or the same as those exerted by the reference hand (Experiment 2).Matching error was biased towards the direction of digit tangential forces: thumb CoP was placed higher than the index finger CoP when thumb and index finger Ftan were directed upward and downward, respectively, and vice versa (p < 0.001). However, matching error was not dependent on whether the reference and test hand exerted similar or different forces. We propose that the expected sensory consequence of motor commands for tangential forces in opposite directions overrides estimation of fingertip position through haptic sensory feedback. PMID- 25136306 TI - Physical and neural entrainment to rhythm: human sensorimotor coordination across tasks and effector systems. AB - The human sensorimotor system can be readily entrained to environmental rhythms, through multiple sensory modalities. In this review, we provide an overview of theories of timekeeping that make this neuroentrainment possible. First, we present recent evidence that contests the assumptions made in classic timekeeper models. The role of state estimation, sensory feedback and movement parameters on the organization of sensorimotor timing are discussed in the context of recent experiments that examined simultaneous timing and force control. This discussion is extended to the study of coordinated multi-effector movements and how they may be entrained. PMID- 25136307 TI - Subliminal cues bias perception of facial affect in patients with social phobia: evidence for enhanced unconscious threat processing. AB - Socially anxious individuals have been shown to exhibit altered processing of facial affect, especially expressions signaling threat. Enhanced unaware processing has been suggested an important mechanism which may give rise to anxious conscious cognition and behavior. This study investigated whether individuals with social anxiety disorder (SAD) are perceptually more vulnerable to the biasing effects of subliminal threat cues compared to healthy controls. In a perceptual judgment task, 23 SAD and 23 matched control participants were asked to rate the affective valence of parametrically manipulated affective expressions ranging from neutral to angry. Each trial was preceded by subliminal presentation of an angry/neutral cue. The SAD group tended to rate target faces as "angry" when the preceding subliminal stimulus was angry vs. neutral, while healthy participants were not biased by the subliminal stimulus presentation. The perceptual bias in SAD was also associated with higher reaction time latencies in the subliminal angry cue condition. The results provide further support for enhanced unconscious threat processing in SAD individuals. The implications for etiology, maintenance, and treatment of SAD are discussed. PMID- 25136305 TI - The influence of expertise on brain activation of the action observation network during anticipation of tennis and volleyball serves. AB - In many daily activities, and especially in sport, it is necessary to predict the effects of others' actions in order to initiate appropriate responses. Recently, researchers have suggested that the action-observation network (AON) including the cerebellum plays an essential role during such anticipation, particularly in sport expert performers. In the present study, we examined the influence of task specific expertise on the AON by investigating differences between two expert groups trained in different sports while anticipating action effects. Altogether, 15 tennis and 16 volleyball experts anticipated the direction of observed tennis and volleyball serves while undergoing functional magnetic resonance imaging (fMRI). The expert group in each sport acted as novice controls in the other sport with which they had only little experience. When contrasting anticipation in both expertise conditions with the corresponding untrained sport, a stronger activation of AON areas (SPL, SMA), and particularly of cerebellar structures, was observed. Furthermore, the neural activation within the cerebellum and the SPL was linearly correlated with participant's anticipation performance, irrespective of the specific expertise. For the SPL, this relationship also holds when an expert performs a domain-specific anticipation task. Notably, the stronger activation of the cerebellum as well as of the SMA and the SPL in the expertise conditions suggests that experts rely on their more fine-tuned perceptual-motor representations that have improved during years of training when anticipating the effects of others' actions in their preferred sport. The association of activation within the SPL and the cerebellum with the task achievement suggests that these areas are the predominant brain sites involved in fast motor predictions. The SPL reflects the processing of domain-specific contextual information and the cerebellum the usage of a predictive internal model to solve the anticipation task. PMID- 25136308 TI - Own-race and own-age biases facilitate visual awareness of faces under interocular suppression. AB - The detection of a face in a visual scene is the first stage in the face processing hierarchy. Although all subsequent, more elaborate face processing depends on the initial detection of a face, surprisingly little is known about the perceptual mechanisms underlying face detection. Recent evidence suggests that relatively hard-wired face detection mechanisms are broadly tuned to all face-like visual patterns as long as they respect the typical spatial configuration of the eyes above the mouth. Here, we qualify this notion by showing that face detection mechanisms are also sensitive to face shape and facial surface reflectance properties. We used continuous flash suppression (CFS) to render faces invisible at the beginning of a trial and measured the time upright and inverted faces needed to break into awareness. Young Caucasian adult observers were presented with faces from their own race or from another race (race experiment) and with faces from their own age group or from another age group (age experiment). Faces matching the observers' own race and age group were detected more quickly. Moreover, the advantage of upright over inverted faces in overcoming CFS, i.e., the face inversion effect (FIE), was larger for own-race and own-age faces. These results demonstrate that differences in face shape and surface reflectance influence access to awareness and configural face processing at the initial detection stage. Although we did not collect data from observers of another race or age group, these findings are a first indication that face detection mechanisms are shaped by visual experience with faces from one's own social group. Such experience-based fine-tuning of face detection mechanisms may equip in-group faces with a competitive advantage for access to conscious awareness. PMID- 25136309 TI - The role of literal meaning in figurative language comprehension: evidence from masked priming ERP. AB - The role of literal meaning during the construction of meaning that goes beyond pure literal composition was investigated by combining cross-modal masked priming and ERPs. This experimental design was chosen to compare two conflicting theoretical positions on this topic. The indirect access account claims that literal aspects are processed first, and additional meaning components are computed only if no satisfactory interpretation is reached. In contrast, the direct access approach argues that figurative aspects can be accessed immediately. We presented metaphors (These lawyers are hyenas, Experiment 1a and 1b) and producer-for-product metonymies (The boy read Boll, Experiment 2a and 2b) with and without a prime word that was semantically relevant to the literal meaning of the target word (furry and talented, respectively). In the presentation without priming, metaphors revealed a biphasic N400-Late Positivity pattern, while metonymies showed an N400 only. We interpret the findings within a two-phase language architecture where contextual expectations guide initial access (N400) and precede pragmatic adjustment resulting in reconceptualization (Late Positivity). With masked priming, the N400-difference was reduced for metaphors and vanished for metonymies. This speaks against the direct access view that predicts a facilitating effect for the literal condition only and hence would predict the N400-difference to increase. The results are more consistent with indirect access accounts that argue for facilitation effects for both conditions and consequently for consistent or even smaller N400-amplitude differences. This combined masked priming ERP paradigm therefore yields new insights into the role of literal meaning in the online composition of figurative language. PMID- 25136310 TI - Devaluation and sequential decisions: linking goal-directed and model-based behavior. AB - In experimental psychology different experiments have been developed to assess goal-directed as compared to habitual control over instrumental decisions. Similar to animal studies selective devaluation procedures have been used. More recently sequential decision-making tasks have been designed to assess the degree of goal-directed vs. habitual choice behavior in terms of an influential computational theory of model-based compared to model-free behavioral control. As recently suggested, different measurements are thought to reflect the same construct. Yet, there has been no attempt to directly assess the construct validity of these different measurements. In the present study, we used a devaluation paradigm and a sequential decision-making task to address this question of construct validity in a sample of 18 healthy male human participants. Correlational analysis revealed a positive association between model-based choices during sequential decisions and goal-directed behavior after devaluation suggesting a single framework underlying both operationalizations and speaking in favor of construct validity of both measurement approaches. Up to now, this has been merely assumed but never been directly tested in humans. PMID- 25136312 TI - Efficient foot motor control by Neymar's brain. AB - How very long-term (over many years) motor skill training shapes internal motor representation remains poorly understood. We provide valuable evidence that the football brain of Neymar da Silva Santos Junior (the Brasilian footballer) recruits very limited neural resources in the motor-cortical foot regions during foot movements. We scanned his brain activity with a 3-tesla functional magnetic resonance imaging (fMRI) while he rotated his right ankle at 1 Hz. We also scanned brain activity when three other age-controlled professional footballers, two top-athlete swimmers and one amateur footballer performed the identical task. A comparison was made between Neymar's brain activity with that obtained from the others. We found activations in the left medial-wall foot motor regions during the foot movements consistently across all participants. However, the size and intensity of medial-wall activity was smaller in the four professional footballers than in the three other participants, despite no difference in amount of foot movement. Surprisingly, the reduced recruitment of medial-wall foot motor regions became apparent in Neymar. His medial-wall activity was smallest among all participants with absolutely no difference in amount of foot movement. Neymar may efficiently control given foot movements probably by largely conserving motor cortical neural resources. We discuss this possibility in terms of over-years motor skill training effect, use-dependent plasticity, and efficient motor control. PMID- 25136311 TI - Functional MRI activation in white matter during the Symbol Digit Modalities Test. AB - BACKGROUND: Recent evidence shows that functional magnetic resonance imaging (fMRI) can detect activation in white matter (WM). Such advances have important implications for understanding WM dysfunction. A key step in linking neuroimaging advances to the evaluation of clinical disorders is to examine whether WM activation can be detected at the individual level during clinical tests associated with WM function. We used an adapted Symbol Digit Modalities Test (SDMT) in a 4T fMRI study of healthy adults. RESULTS: RESULTS from 17 healthy individuals revealed WM activation in 88% of participants (15/17). The activation was in either the corpus callosum (anterior and/or posterior) or internal capsule (left and/or right). CONCLUSIONS: The findings link advances in fMRI to an established clinical test of WM function. Future work should focus on evaluating patients with WM dysfunction. PMID- 25136313 TI - From neuronal populations to behavior: a computational journey. PMID- 25136314 TI - Depth information in natural environments derived from optic flow by insect motion detection system: a model analysis. AB - Knowing the depth structure of the environment is crucial for moving animals in many behavioral contexts, such as collision avoidance, targeting objects, or spatial navigation. An important source of depth information is motion parallax. This powerful cue is generated on the eyes during translatory self-motion with the retinal images of nearby objects moving faster than those of distant ones. To investigate how the visual motion pathway represents motion-based depth information we analyzed its responses to image sequences recorded in natural cluttered environments with a wide range of depth structures. The analysis was done on the basis of an experimentally validated model of the visual motion pathway of insects, with its core elements being correlation-type elementary motion detectors (EMDs). It is the key result of our analysis that the absolute EMD responses, i.e., the motion energy profile, represent the contrast-weighted nearness of environmental structures during translatory self-motion at a roughly constant velocity. In other words, the output of the EMD array highlights contours of nearby objects. This conclusion is largely independent of the scale over which EMDs are spatially pooled and was corroborated by scrutinizing the motion energy profile after eliminating the depth structure from the natural image sequences. Hence, the well-established dependence of correlation-type EMDs on both velocity and textural properties of motion stimuli appears to be advantageous for representing behaviorally relevant information about the environment in a computationally parsimonious way. PMID- 25136315 TI - Resistive and reactive changes to the impedance of intracortical microelectrodes can be mitigated with polyethylene glycol under acute in vitro and in vivo settings. AB - The reactive response of brain tissue to implantable intracortical microelectrodes is thought to negatively affect their recordable signal quality and impedance, resulting in unreliable longitudinal performance. The relationship between the progression of the reactive tissue into a glial scar and the decline in device performance is unclear. We show that exposure to a model protein solution in vitro and acute implantation result in both resistive and capacitive changes to electrode impedance, rather than purely resistive changes. We also show that applying 4000 MW polyethylene glycol (PEG) prevents impedance increases in vitro, and reduces the percent change in impedance in vivo following implantation. Our results highlight the importance of considering the contributions of non-cellular components to the decline in neural microelectrode performance, and present a proof of concept for using a simple dip-coated PEG film to modulate changes in microelectrode impedance. PMID- 25136316 TI - The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress. AB - Age-related macular degeneration (AMD) is one retinal aging process that may lead to irreversible vision loss in the elderly. Its pathogenesis remains unclear, but oxidative stress inducing retinal pigment epithelial (RPE) cells damage is perhaps responsible for the aging sequence of retina and may play an important role in macular degeneration. In this study, we have reprogrammed T cells from patients with dry type AMD into induced pluripotent stem cells (iPSCs) via integration-free episomal vectors and differentiated them into RPE cells that were used as an expandable platform for investigating pathogenesis of the AMD and in-vitro drug screening. These patient-derived RPEs with the AMD-associated background (AMD-RPEs) exhibited reduced antioxidant ability, compared with normal RPE cells. Among several screened candidate drugs, curcumin caused most significant reduction of ROS in AMD-RPEs. Pre-treatment of curcumin protected these AMD-RPEs from H2O2-induced cell death and also increased the cytoprotective effect against the oxidative stress of H2O2 through the reduction of ROS levels. In addition, curcumin with its versatile activities modulated the expression of many oxidative stress-regulating genes such as PDGF, VEGF, IGFBP-2, HO1, SOD2, and GPX1. Our findings indicated that the RPE cells derived from AMD patients have decreased antioxidative defense, making RPE cells more susceptible to oxidative damage and thereby leading to AMD formation. Curcumin represented an ideal drug that can effectively restore the neuronal functions in AMD patient derived RPE cells, rendering this drug an effective option for macular degeneration therapy and an agent against aging-associated oxidative stress. PMID- 25136317 TI - Subtype and regional-specific neuroinflammation in sporadic creutzfeldt-jakob disease. AB - The present study identifies deregulated cytokines and mediators of the immune response in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls. Deregulated genes include pro- and anti-inflammatory cytokines, toll-like receptors, colony stimulating factors, cathepsins, members of the complement system, and members of the integrin and CTL/CTLD family with particular regional and sCJD subtype patterns. Analysis of cytokines and mediators at protein level shows expression of selected molecules and receptors in neurons, in astrocytes, and/or in microglia, thus suggesting interactions between neurons and glial cells, mainly microglia, in the neuroinflammatory response in sCJD. Similar inflammatory responses have been shown in the tg340 sCJD MM1 mice, revealing a progressive deregulation of inflammatory mediators with disease progression. Yet, inflammatory molecules involved are subjected to species differences in humans and mice. Moreover, inflammatory-related cell signaling pathways NFkappaB/IKK and JAK/STAT are activated in sCJD and sCJD MM1 mice. Together, the present observations show a self-sustained complex inflammatory and inflammatory-related responses occurring already at early clinical stages in animal model and dramatically progressing at advanced stages of sCJD. Considering this scenario, measures tailored to modulate (activate or inhibit) specific molecules could be therapeutic options in CJD. PMID- 25136318 TI - The pleural mesothelium in development and disease. AB - The pleural mesothelium, derived from the embryonic mesoderm, is formed by a metabolically active monolayer of cells that blanket the chest wall and lungs on the parietal and visceral surfaces, respectively. The pleura and lungs are formed as a result of an intricate relationship between the mesoderm and the endoderm during development. Mesenchymal signaling pathways such as Wnt/B-catenin, Bmp4, and sonic hedgehog appear to be quintessential for lung development. Pleural Mesothelial Cells (PMCs) are known to express Wilms tumor-1 (Wt1) gene and in lineage labeling studies of the developing embryo, PMCs were found to track into the lung parenchyma and undergo mesothelial-mesenchymal transition (MMT) to form alpha-smooth muscle actin (alpha-SMA)-positive cells of the mesenchyme and vasculature. There is definite evidence that mesothelial cells can differentiate and this seems to play an important role in pleural and parenchymal pathologies. Mesothelial cells can differentiate into adipocytes, chondrocytes, and osteoblasts; and have been shown to clonally generate fibroblasts and smooth muscle cells in murine models. This supports the possibility that they may also modulate lung injury-repair by re-activation of developmental programs in the adult reflecting an altered recapitulation of development, with implications for regenerative biology of the lung. In a mouse model of lung fibrosis using lineage tracing studies, PMCs lost their polarity and cell-cell junctional complexes, migrated into lung parenchyma, and underwent phenotypic transition into myofibroblasts in response to the pro-fibrotic mediator, transforming growth factor-beta1 (TGF-beta1). However, intra-pleural heme-oxygenase-1 (HO-1) induction inhibited PMC migration after intra-tracheal fibrogenic injury. Intra pleural fluorescein isothiocyanate labeled nanoparticles decorated with a surface antibody to mesothelin, a surface marker of mesothelial cells, migrate into the lung parenchyma with PMCs supporting a potential role for pleural based therapies to modulate pleural mesothelial activation and parenchymal disease progression. PMID- 25136319 TI - Congenital heart malformations induced by hemodynamic altering surgical interventions. AB - Embryonic heart formation results from a dynamic interplay between genetic and environmental factors. Blood flow during early embryonic stages plays a critical role in heart development, as interactions between flow and cardiac tissues generate biomechanical forces that modulate cardiac growth and remodeling. Normal hemodynamic conditions are essential for proper cardiac development, while altered blood flow induced by surgical manipulations in animal models result in heart defects similar to those seen in humans with congenital heart disease. This review compares the altered hemodynamics, changes in tissue properties, and cardiac defects reported after common surgical interventions that alter hemodynamics in the early chick embryo, and shows that interventions produce a wide spectrum of cardiac defects. Vitelline vein ligation and left atrial ligation decrease blood pressure and flow; and outflow tract banding increases blood pressure and flow velocities. These three surgical interventions result in many of the same cardiac defects, which indicate that the altered hemodynamics interfere with common looping, septation and valve formation processes that occur after intervention and that shape the four-chambered heart. While many similar defects develop after the interventions, the varying degrees of hemodynamic load alteration among the three interventions also result in varying incidence and severity of cardiac defects, indicating that the hemodynamic modulation of cardiac developmental processes is strongly dependent on hemodynamic load. PMID- 25136322 TI - Reentrant processing mediates object substitution masking: comment on Poder (2013). AB - Object-substitution masking (OSM) occurs when a target stimulus and a surrounding mask are displayed briefly together, and the display then continues with the mask alone. Target identification is accurate when the stimuli co-terminate but is progressively impaired as the duration of the trailing mask is increased. In reentrant accounts, OSM is said to arise from iterative exchanges between brain regions connected by two-way pathways. In an alternative account, OSM is explained on the basis of exclusively feed-forward processes, without recourse to reentry. Here I show that the feed-forward account runs afoul of the extant phenomenological, behavioral, brain-imaging, and electrophysiological evidence. Further, the feed-forward assumption that masking occurs when attention finds a degraded target is shown to be entirely ad hoc. In contrast, the evidence is uniformly consistent with a reentrant-processing account of OSM. PMID- 25136321 TI - Processing of sub- and supra-second intervals in the primate brain results from the calibration of neuronal oscillators via sensory, motor, and feedback processes. AB - The processing of time intervals in the sub- to supra-second range by the brain is critical for the interaction of primates with their surroundings in activities, such as foraging and hunting. For an accurate processing of time intervals by the brain, representation of physical time within neuronal circuits is necessary. I propose that time dimension of the physical surrounding is represented in the brain by different types of neuronal oscillators, generating spikes or spike bursts at regular intervals. The proposed oscillators include the pacemaker neurons, tonic inputs, and synchronized excitation and inhibition of inter-connected neurons. Oscillators, which are built inside various circuits of brain, help to form modular clocks, processing time intervals or other temporal characteristics specific to functions of a circuit. Relative or absolute duration is represented within neuronal oscillators by "neural temporal unit," defined as the interval between regularly occurring spikes or spike bursts. Oscillator output is processed to produce changes in activities of neurons, named frequency modulator neuron, wired within a separate module, represented by the rate of change in frequency, and frequency of activities, proposed to encode time intervals. Inbuilt oscillators are calibrated by (a) feedback processes, (b) input of time intervals resulting from rhythmic external sensory stimulation, and (c) synchronous effects of feedback processes and evoked sensory activity. A single active clock is proposed per circuit, which is calibrated by one or more mechanisms. Multiple calibration mechanisms, inbuilt oscillators, and the presence of modular connections prevent a complete loss of interval timing functions of the brain. PMID- 25136323 TI - Embodied niche construction in the hominin lineage: semiotic structure and sustained attention in human embodied cognition. AB - Human evolution unfolded through a rather distinctive, dynamically constructed ecological niche. The human niche is not only generally terrestrial in habitat, while being flexibly and extensively heterotrophic in food-web connections. It is also defined by semiotically structured and structuring embodied cognitive interfaces, connecting the individual organism with the wider environment. The embodied dimensions of niche-population co-evolution have long involved semiotic system construction, which I hypothesize to be an evolutionarily primitive aspect of learning and higher-level cognitive integration and attention in the great apes and humans alike. A clearly pre-linguistic form of semiotic cognitive structuration is suggested to involve recursively learned and constructed object icons. Higher-level cognitive iconic representation of visually, auditorily, or haptically perceived extrasomatic objects would be learned and evoked through indexical connections to proprioceptive and affective somatic states. Thus, private cognitive signs would be defined, not only by their learned and perceived extrasomatic referents, but also by their associations to iconically represented somatic states. This evolutionary modification of animal associative learning is suggested to be adaptive in ecological niches occupied by long-lived, large bodied ape species, facilitating memory construction and recall in highly varied foraging and social contexts, while sustaining selective attention during goal directed behavioral sequences. The embodied niche construction (ENC) hypothesis of human evolution posits that in the early hominin lineage, natural selection further modified the ancestral ape semiotic adaptations, favoring the recursive structuration of concise iconic narratives of embodied interaction with the environment. PMID- 25136324 TI - Mindfulness-Based Functional Therapy: a preliminary open trial of an integrated model of care for people with persistent low back pain. AB - OBJECTIVES: This pilot study investigated the feasibility and clinical utility of implementing a novel, evidence-informed, interdisciplinary group intervention Mindfulness Based Functional Therapy (MBFT)-for the management of persistent low back pain (LBP) in primary care. MBFT aimed to improve physical and psychological functioning in patients with persistent LBP. DESIGN: A single-group repeated measures design was utilized to gather data about feasibility, effect sizes, clinically significant changes and patient satisfaction. SETTING: A community sample of 16 adults (75% female), mean (SD) age 47.00 (9.12) years (range 26-65 years), with mean (SD) LBP duration of 8.00 (9.00) years participated, using a simulated primary care setting at Curtin University in Australia. INTERVENTION: MBFT is an 8-week group intervention co-facilitated by psychology and physiotherapy disciplines. Content includes: mindfulness meditation training, cognitive-functional physiotherapeutic movement retraining, pain education, and group support. MAIN OUTCOME MEASURES: Several validated self-report measures were used to assess functional disability, emotional functioning, mindfulness, pain catastrophizing, health-related quality of life at baseline, post-intervention, and 6 months follow-up. RESULTS: Adherence and satisfaction was high, with 85% of participants highly satisfied with MBFT. Clinical significance analysis and effect size estimates showed improvements in a number of variables, including pain catastrophizing, physical functioning, role limitations due to physical condition, and depression, although these may have occurred due to non intervention effects. CONCLUSIONS: MBFT is feasible to implement in primary care. Preliminary findings suggest that a randomized controlled trial is warranted to investigate its efficacy in improving physical and emotional functioning in people with disabling persistent LBP. PMID- 25136320 TI - Gene * Environment interactions in autism spectrum disorders: role of epigenetic mechanisms. AB - Several studies support currently the hypothesis that autism etiology is based on a polygenic and epistatic model. However, despite advances in epidemiological, molecular and clinical genetics, the genetic risk factors remain difficult to identify, with the exception of a few chromosomal disorders and several single gene disorders associated with an increased risk for autism. Furthermore, several studies suggest a role of environmental factors in autism spectrum disorders (ASD). First, arguments for a genetic contribution to autism, based on updated family and twin studies, are examined. Second, a review of possible prenatal, perinatal, and postnatal environmental risk factors for ASD are presented. Then, the hypotheses are discussed concerning the underlying mechanisms related to a role of environmental factors in the development of ASD in association with genetic factors. In particular, epigenetics as a candidate biological mechanism for gene * environment interactions is considered and the possible role of epigenetic mechanisms reported in genetic disorders associated with ASD is discussed. Furthermore, the example of in utero exposure to valproate provides a good illustration of epigenetic mechanisms involved in ASD and innovative therapeutic strategies. Epigenetic remodeling by environmental factors opens new perspectives for a better understanding, prevention, and early therapeutic intervention of ASD. PMID- 25136326 TI - Proximity and gaze influences facial temperature: a thermal infrared imaging study. AB - Direct gaze and interpersonal proximity are known to lead to changes in psycho physiology, behavior and brain function. We know little, however, about subtler facial reactions such as rise and fall in temperature, which may be sensitive to contextual effects and functional in social interactions. Using thermal infrared imaging cameras 18 female adult participants were filmed at two interpersonal distances (intimate and social) and two gaze conditions (averted and direct). The order of variation in distance was counterbalanced: half the participants experienced a female experimenter's gaze at the social distance first before the intimate distance (a socially "normal" order) and half experienced the intimate distance first and then the social distance (an odd social order). At both distances averted gaze always preceded direct gaze. We found strong correlations in thermal changes between six areas of the face (forehead, chin, cheeks, nose, maxilliary, and periorbital regions) for all experimental conditions and developed a composite measure of thermal shifts for all analyses. Interpersonal proximity led to a thermal rise, but only in the "normal" social order. Direct gaze, compared to averted gaze, led to a thermal increase at both distances with a stronger effect at intimate distance, in both orders of distance variation. Participants reported direct gaze as more intrusive than averted gaze, especially at the intimate distance. These results demonstrate the powerful effects of another person's gaze on psycho-physiological responses, even at a distance and independent of context. PMID- 25136327 TI - Understanding social engagement in autism: being different in perceiving and sharing affordances. AB - In the current paper I will argue that the notion of affordances offers an alternative to theory of mind (ToM) approaches in studying social engagement in general and in explaining social engagement in autism spectrum disorder (ASD) specifically. Affordances are the possibilities for action offered by the environment. In contrast to ToM approaches, the concept of affordances implies the complementarity of person and environment and rejects the dualism of mind and behavior. In line with the Gibsonian idea that a child must eventually perceive the affordances of the environment for others as well for herself in order to become socialized, I will hypothesize that individuals with ASD often do not perceive the same affordances in the environment as other people do and have difficulties perceiving others' affordances. This can lead to a disruption of interpersonal behaviors. I will further argue that the methods for studying social engagement should be adapted if we want to take interaction into account. PMID- 25136325 TI - A bihemispheric autonomic model for traumatic stress effects on health and behavior. AB - A bihemispheric autonomic model (BHAM) may support advanced understanding of traumatic stress effects on physiology and behavior. The model builds on established data showing hemispheric lateralization in management of the autonomic nervous system, and proposes that traumatic stress can produce dominant asymmetry in activity of bilateral homologous brain regions responsible for autonomic management. Rightward and leftward dominant asymmetries are associated with sympathetic high arousal or parasympathetic freeze tendencies, respectively, and return to relative symmetry is associated with improved autonomic regulation. Autonomic auto-calibration for recovery (inverse of Jacksonian dissolution proposed by polyvagal theory) has implications for risk behaviors associated with traumatic life stress. Trauma-induced high arousal may be associated with risk for maladaptive behaviors to attenuate arousal (including abuse of alcohol or sedative-hypnotics). Trauma-induced freeze mode (including callous-unemotional trait) may be associated with low resting heart rate and risk for conduct disorders. The model may explain higher prevalence of leftward hemispheric abnormalities reported in studies of violence. Implications of the BHAM are illustrated through case examples of a military special operations officer with history of traumatic brain injury and post-traumatic stress disorder, and a university student with persisting post-concussion symptoms. Both undertook use of a noninvasive closed-loop neurotechnology - high-resolution, relational, resonance-based, electroencephalic mirroring - with ensuing decrease in hemispheric asymmetry, improvement in heart rate variability, and symptom reduction. Finally, the BHAM aligns with calls for researchers to use brain behavioral constructs (research domain criteria or RDoC, proposed by the National Institutes of Mental Health) as building blocks for assessment and intervention in mental health science. PMID- 25136328 TI - Prospection and emotional memory: how expectation affects emotional memory formation following sleep and wake. AB - Successful prospective memory is necessarily driven by an expectation that encoded information will be relevant in the future, leading to its preferential placement in memory storage. Like expectation, emotional salience is another type of cue that benefits human memory formation. Although separate lines of research suggest that both emotional information and information explicitly expected to be important in the future benefit memory consolidation, it is unknown how expectation affects the processing of emotional information and whether sleep, which is known to maximize memory consolidation, plays a critical role. The purpose of this study was to investigate how expectation would impact the consolidation of emotionally salient content, and whether this impact would differ across delays of sleep and wake. Participants encoded scenes containing an emotionally charged negative or neutral foreground object placed on a plausible neutral background. After encoding, half of the participants were informed they would later be tested on the scenes (expected condition), while the other half received no information about the test (unexpected condition). At recognition, following a 12-h delay of sleep or wakefulness, the scene components (objects and backgrounds) were presented separately and one at a time, and participants were asked to determine if each component was old or new. Results revealed a greater disparity for memory of negative objects over their paired neutral backgrounds for both the sleep and wake groups when the memory test was expected compared to when it was unexpected, while neutral memory remained unchanged. Analyzing each group separately, the wake group showed a threefold increase in the magnitude of this object/background trade-off for emotional scenes when the memory test was expected compared to when it was unexpected, while those who slept performed similarly across conditions. These results suggest that emotional salience and expectation cues interact to benefit emotional memory consolidation during a delay of wakefulness. The sleeping brain, however, may automatically tag emotionally salient information as important, such that explicit instruction of an upcoming memory test does not further improve memory performance. PMID- 25136330 TI - Bone status in patients with epilepsy: relationship to markers of bone remodeling. AB - Patients with epilepsy and treated with antiepileptic drugs (AEDs) may develop metabolic bone disease; however, the exact pathogenesis of bone loss with AEDs is still unclear. Included were 75 adults with epilepsy (mean age: 31.90 +/- 5.62 years; duration of treatment with AEDs: 10.57 +/- 3.55 years) and 40 matched healthy controls. Bone mineral content (BMC) and bone mineral densities (BMD) of the femoral neck and lumbar spine were measured using dual-energy X-ray absorptiometry (DEXA). Blood samples were analyzed for calcium, magnesium, phosphate, alkaline phosphatase (ALP), 25-hydroxy vitamin D (25OHD), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin (OPG), and OPG/RANKL ratio (markers of bone remodeling). Compared to controls, patients had lower BMD, BMC, Z-score, and T-score at the femoral neck and lumbar spine (all p < 0.001). Seventy-two percent and 29.33% of patients had osteoporosis of the lumbar spine and femoral neck. Patients had significantly lower serum calcium, 25(OH)D, and OPG and higher ALP, sRANKL levels, and sRANKL/OPG (all p < 0.001). Fifty-two percent of patients had hypocalcemia, 93% had hypovitaminosis D, 31% had high levels of sRANKL, and 49% had low levels of OPG. No differences were identified between DEXA and laboratory results in relation to the type, dose, or serum levels of AEDs. BMD at the femoral neck and lumbar spine were found to be correlated with the duration of illness (p = 0.043; p = 0.010), duration of treatment with AEDs (p < 0.001; p = 0.012), and serum levels of 25(OH)D (p = 0.042; p = 0.010), sRANKLs (p = 0.005; p = 0.01), and OPG (p = 0.006; p = 0.01). In linear regression analysis and after adjusting for gender, age, weight, duration, and number of AEDs, we observed an association between BMD, 25(OH)D (p = 0.04) and sRANKL (p = 0.03) concentrations. We conclude that AEDs may compromise bone health through disturbance of mineral metabolism and acceleration of bone turnover mechanisms. PMID- 25136329 TI - The sleepy teenager - diagnostic challenges. AB - The sleepy teenager puts the doctor in a, often tricky, situation where it must be decided if we deal with normal physiology or if we should suspect pathological conditions. What medical investigations are proper to consider? What differential diagnoses should be considered in the first place? And what tools do we actually have? The symptoms and problems that usually are presented at the clinical visit can be both of medical and psychosocial character - and actually they are often a mixture of both. Subsequently, the challenge to investigate the sleepy teenager often includes the examination of a complex behavioral pattern. It is important to train and develop diagnostic skills and to realize that the physiological or pathological conditions that can cause the symptoms may have different explanations. Research in sleep disorders has shown different pathological mechanisms congruent with the variations in the clinical picture. There are probably also different patterns of involved neuronal circuits although common pathways may exist. The whole picture remains to be drawn in this interesting and challenging area. PMID- 25136331 TI - Brain Injury Markers: Where are We? PMID- 25136332 TI - Ipsen 5i is a Novel Potent Pharmacoperone for Intracellularly Retained Melanocortin-4 Receptor Mutants. AB - Inactivating mutations of the melanocortin-4 receptor (MC4R) cause early-onset severe obesity in humans. Comprehensive functional studies show that most of the inactivating mutants of the MC4R are retained intracellularly. In the present study, we investigated whether a small molecule inverse agonist of the MC4R, Ipsen 5i, could act as a pharmacoperone and correct the cell surface expression and function of intracellularly retained mutant MC4Rs using multiple cell lines, including HEK293 and two neuronal cell lines. We showed that Ipsen 5i rescued the cell surface expression of all 11 intracellularly retained mutant MC4Rs studied herein in at least one cell line. Ipsen 5i functionally rescued seven mutants in all cell lines used. One mutant (Y157S) was functionally rescued in HEK293 cells but not in the two neuronal cell lines. Ipsen 5i increased cell surface expression of three mutants (S58C, G98R, and F261S) but did not affect signaling. Ipsen 5i had no effect on mutant MC4Rs with other defects (Delta88-92, D90N, I102S) or no defect (N274S). It also did not affect trafficking of a misrouted MC3R mutant (I335S). Cell impermeable peptide ligands of the MC4R or cell permeable small molecule ligand of delta opioid receptor could not rescue misrouted mutant MC4R. In summary, we demonstrated that Ipsen 5i was a novel potent pharmacoperone of the MC4R, correcting trafficking and signaling of a significant portion (73%) of intracellularly retained mutants. Additional studies are needed to demonstrate its in vivo efficacy. PMID- 25136333 TI - Comparative analysis of Salmonella susceptibility and tolerance to the biocide chlorhexidine identifies a complex cellular defense network. AB - Chlorhexidine is one of the most widely used biocides in health and agricultural settings as well as in the modern food industry. It is a cationic biocide of the biguanide class. Details of its mechanism of action are largely unknown. The frequent use of chlorhexidine has been questioned recently, amidst concerns that an overuse of this compound may select for bacteria displaying an altered susceptibility to antimicrobials, including clinically important anti-bacterial agents. We generated a Salmonella enterica serovar Typhimurium isolate (ST24(CHX)) that exhibited a high-level tolerant phenotype to chlorhexidine, following several rounds of in vitro selection, using sub-lethal concentrations of the biocide. This mutant showed altered suceptibility to a panel of clinically important antimicrobial compounds. Here we describe a genomic, transcriptomic, proteomic, and phenotypic analysis of the chlorhexidine tolerant S. Typhimurium compared with its isogenic sensitive progenitor. Results from this study describe a chlorhexidine defense network that functions in both the reference chlorhexidine sensitive isolate and the tolerant mutant. The defense network involved multiple cell targets including those associated with the synthesis and modification of the cell wall, the SOS response, virulence, and a shift in cellular metabolism toward anoxic pathways, some of which were regulated by CreB and Fur. In addition, results indicated that chlorhexidine tolerance was associated with more extensive modifications of the same cellular processes involved in this proposed network, as well as a divergent defense response involving the up-regulation of additional targets such as the flagellar apparatus and an altered cellular phosphate metabolism. These data show that sub-lethal concentrations of chlorhexidine induce distinct changes in exposed Salmonella, and our findings provide insights into the mechanisms of action and tolerance to this biocidal agent. PMID- 25136335 TI - Transposon-mediated directed mutation controlled by DNA binding proteins in Escherichia coli. PMID- 25136334 TI - Engineering processive DNA polymerases with maximum benefit at minimum cost. AB - DNA polymerases need to be engineered to achieve optimal performance for biotechnological applications, which often require high fidelity replication when using modified nucleotides and when replicating difficult DNA sequences. These tasks are achieved for the bacteriophage T4 DNA polymerase by replacing leucine with methionine in the highly conserved Motif A sequence (L412M). The costs are minimal. Although base substitution errors increase moderately, accuracy is maintained for templates with mono- and dinucleotide repeats while replication efficiency is enhanced. The L412M substitution increases intrinsic processivity and addition of phage T4 clamp and single-stranded DNA binding proteins further enhance the ability of the phage T4 L412M-DNA polymerase to replicate all types of difficult DNA sequences. Increased pyrophosphorolysis is a drawback of increased processivity, but pyrophosphorolysis is curbed by adding an inorganic pyrophosphatase or divalent metal cations, Mn(2+) or Ca(2+). In the absence of pyrophosphorolysis inhibitors, the T4 L412M-DNA polymerase catalyzed sequence dependent pyrophosphorolysis under DNA sequencing conditions. The sequence specificity of the pyrophosphorolysis reaction provides insights into how the T4 DNA polymerase switches between nucleotide incorporation, pyrophosphorolysis and proofreading pathways. The L-to-M substitution was also tested in the yeast DNA polymerases delta and alpha. Because the mutant DNA polymerases displayed similar characteristics, we propose that amino acid substitutions in Motif A have the potential to increase processivity and to enhance performance in biotechnological applications. An underlying theme in this chapter is the use of genetic methods to identify mutant DNA polymerases with potential for use in current and future biotechnological applications. PMID- 25136338 TI - A novel thermostable polymerase for RNA and DNA loop-mediated isothermal amplification (LAMP). AB - Meeting the goal of providing point of care (POC) tests for molecular detection of pathogens in low resource settings places stringent demands on all aspects of the technology. OmniAmp DNA polymerase (Pol) is a thermostable viral enzyme that enables true POC use in clinics or in the field by overcoming important barriers to isothermal amplification. In this paper, we describe the multiple advantages of OmniAmp Pol as an isothermal amplification enzyme and provide examples of its use in loop-mediated isothermal amplification (LAMP) for pathogen detection. The inherent reverse transcriptase activity of OmniAmp Pol allows single enzyme detection of RNA targets in RT-LAMP. Common methods of nucleic acid amplification are highly susceptible to sample contaminants, necessitating elaborate nucleic acid purification protocols that are incompatible with POC or field use. OmniAmp Pol was found to be less inhibited by whole blood components typical in certain crude sample preparations. Moreover, the thermostability of the enzyme compared to alternative DNA polymerases (Bst) and reverse transcriptases allows pretreatment of complete reaction mixes immediately prior to amplification, which facilitates amplification of highly structured genome regions. Compared to Bst, OmniAmp Pol has a faster time to result, particularly with more dilute templates. Molecular diagnostics in field settings can be challenging due to the lack of refrigeration. The stability of OmniAmp Pol is compatible with a dry format that enables long term storage at ambient temperatures. A final requirement for field operability is compatibility with either commonly available instruments or, in other cases, a simple, inexpensive, portable detection mode requiring minimal training or power. Detection of amplification products is shown using lateral flow strips and analysis on a real-time PCR instrument. Results of this study show that OmniAmp Pol is ideally suited for low resource molecular detection of pathogens. PMID- 25136336 TI - Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ. AB - Human infections by the bacterial pathogen Salmonella enterica represent major disease burdens worldwide. This highly ubiquitous species consists of more than 2600 different serovars that can be divided into typhoidal and non-typhoidal Salmonella (NTS) serovars. Despite their genetic similarity, these two groups elicit very different diseases and distinct immune responses in humans. Comparative analyses of the genomes of multiple Salmonella serovars have begun to explain the basis of the variation in disease manifestations. Recent advances in modeling both enteric fever and intestinal gastroenteritis in mice will facilitate investigation into both the bacterial- and host-mediated mechanisms involved in salmonelloses. Understanding the genetic and molecular mechanisms responsible for differences in disease outcome will augment our understanding of Salmonella pathogenesis, host immunity, and the molecular basis of host specificity. This review outlines the differences in epidemiology, clinical manifestations, and the human immune response to typhoidal and NTS infections and summarizes the current thinking on why these differences might exist. PMID- 25136337 TI - Comparative proteome analysis reveals conserved and specific adaptation patterns of Staphylococcus aureus after internalization by different types of human non professional phagocytic host cells. AB - Staphylococcus aureus is a human pathogen that can cause a wide range of diseases. Although formerly regarded as extracellular pathogen, it has been shown that S. aureus can also be internalized by host cells and persist within these cells. In the present study, we comparatively analyzed survival and physiological adaptation of S. aureus HG001 after internalization by two human lung epithelial cell lines (S9 and A549), and human embryonic kidney cells (HEK 293). Combining enrichment of bacteria from host-pathogen assays by cell sorting and quantitation of the pathogen's proteome by mass spectrometry we characterized S. aureus adaptation during the initial phase between 2.5 h and 6.5 h post-infection. Starting with about 2 * 10(6) bacteria, roughly 1450 S. aureus proteins, including virulence factors and metabolic enzymes were identified by spectral comparison and classical database searches. Most of the bacterial adaptation reactions, such as decreased levels of ribosomal proteins and metabolic enzymes or increased amounts of proteins involved in arginine and lysine biosynthesis, enzymes coding for terminal oxidases and stress responsive proteins or activation of the sigma factor SigB were observed after internalization into any of the three cell lines studied. However, differences were noted in central carbon metabolism including regulation of fermentation and threonine degradation. Since these differences coincided with different intracellular growth behavior, complementary profiling of the metabolome of the different non-infected host cell types was performed. This revealed similar levels of intracellular glucose but host cell specific differences in the amounts of amino acids such as glycine, threonine or glutamate. With this comparative study we provide an impression of the common and specific features of the adaptation of S. aureus HG001 to specific host cell environments as a starting point for follow-up studies with different strain isolates and regulatory mutants. PMID- 25136339 TI - Not just who, but how many: the importance of partner abundance in reef coral symbioses. AB - The performance and function of reef corals depends on the genetic identity of their symbiotic algal partners, with some symbionts providing greater benefits (e.g., photosynthate, thermotolerance) than others. However, these interaction outcomes may also depend on partner abundance, with differences in the total number of symbionts changing the net benefit to the coral host, depending on the particular environmental conditions. We suggest that symbiont abundance is a fundamental aspect of the dynamic interface between reef corals and the abiotic environment that ultimately determines the benefits, costs, and functional responses of these symbioses. This density-dependent framework suggests that corals may regulate the size of their symbiont pool to match microhabitat specific optima, which may contribute to the high spatiotemporal variability in symbiont abundance observed within and among colonies and reefs. Differences in symbiont standing stock may subsequently explain variation in energetics, growth, reproduction, and stress susceptibility, and may mediate the impacts of environmental change on these outcomes. However, the importance of symbiont abundance has received relatively little recognition, possibly because commonly used metrics based on surface area (e.g., symbiont cells cm(-2)) may be only weakly linked to biological phenomena and are difficult to compare across studies. We suggest that normalizing symbionts to biological host parameters, such as units of protein or numbers of host cells, will more clearly elucidate the functional role of symbiont abundance in reef coral symbioses. In this article, we generate testable hypotheses regarding the importance of symbiont abundance by first discussing different metrics and their potential links to symbiosis performance and breakdown, and then describing how natural variability and dynamics of symbiont communities may help explain ecological patterns on coral reefs and predict responses to environmental change. PMID- 25136341 TI - Trypanosoma cruzi-Host Cell Interaction. PMID- 25136340 TI - Fold modulating function: bacterial toxins to functional amyloids. AB - Many bacteria produce cytolytic toxins that target host cells or other competing microbes. It is well known that environmental factors control toxin expression, however, recent work suggests that some bacteria manipulate the fold of these protein toxins to control their function. The beta-sheet rich amyloid fold is a highly stable ordered aggregate that many toxins form in response to specific environmental conditions. When in the amyloid state, toxins become inert, losing the cytolytic activity they display in the soluble form. Emerging evidence suggest that some amyloids function as toxin storage systems until they are again needed, while other bacteria utilize amyloids as a structural matrix component of biofilms. This amyloid matrix component facilitates resistance to biofilm disruptive challenges. The bacterial amyloids discussed in this review reveal an elegant system where changes in protein fold and solubility dictate the function of proteins in response to the environment. PMID- 25136343 TI - Extracellular vesicles as therapeutic tools in cardiovascular diseases. AB - Extracellular vesicles (EVs), including microvesicles (MVs) and exosomes, are small vesicles secreted from a wide variety of cells. Whereas MVs are particles released by the outward budding of the plasma membrane, exosomes are derived from endocytic compartments. Secretion of EVs can be enhanced by specific stimuli, and increased plasma circulating levels of EVs have been correlated with pathophysiological situations. MVs, already present in the blood of healthy individuals, are considerably elevated in several cardiovascular diseases associated with inflammation, suggesting that they can mediate deleterious effects such as endothelial dysfunction or thrombosis. Nonetheless, very recent studies also demonstrate that MVs may act as biological information vectors transferring proteins or genetic material to maintain cell homeostasis, favor cell repair, or even promote angiogenesis. Additionally, exosomes have also been shown to have pro-angiogenic and cardio-protective properties. These beneficial effects, therefore, reveal the potential therapeutical use of EVs in the field of cardiovascular medicine and regenerative therapy. In this review, we will provide an update of cellular processes modulated by EVs of specific interest in the treatment of cardiovascular pathologies. A special focus will be made on the morphogen sonic hedgehog (Shh) associated with EVs (EVs(Shh+)), which have been shown to mediate many pro-angiogenic effects. In addition to offer a potential source of cardiovascular markers, therapeutical potential of EVs reveal exciting opportunities to deliver specific agents by non-immunogenic means to cardiovascular system. PMID- 25136344 TI - High atomic weight, high-energy radiation (HZE) induces transcriptional responses shared with conventional stresses in addition to a core "DSB" response specific to clastogenic treatments. AB - Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as "collateral" damage to other cellular components and therefore are not expected to provoke identical responses by the cell. Here we study the effects of two different types of ionizing radiation (IR) treatment, HZE (1 GeV Fe(26+) high mass, high charge, and high energy relativistic particles) and gamma photons, on the transcriptome of Arabidopsis thaliana seedlings. Both types of IR induce small clusters of radicals that can result in the formation of double strand breaks (DSBs), but HZE also produces linear arrays of extremely clustered damage. We performed these experiments across a range of time points (1.5-24 h after irradiation) in both wild-type plants and in mutants defective in the DSB-sensing protein kinase ATM. The two types of IR exhibit a shared double strand break-repair-related damage response, although they differ slightly in the timing, degree, and ATM-dependence of the response. The ATM-dependent, DNA metabolism-related transcripts of the "DSB response" were also induced by other DNA damaging agents, but were not induced by conventional stresses. Both Gamma and HZE irradiation induced, at 24 h post-irradiation, ATM-dependent transcripts associated with a variety of conventional stresses; these were overrepresented for pathogen response, rather than DNA metabolism. In contrast, only HZE-irradiated plants, at 1.5 h after irradiation, exhibited an additional and very extensive transcriptional response, shared with plants experiencing "extended night." This response was not apparent in gamma-irradiated plants. PMID- 25136345 TI - Divisions of labor in the thiamin biosynthetic pathway among organs of maize. AB - The B vitamin thiamin is essential for central metabolism in all cellular organisms including plants. While plants synthesize thiamin de novo, organs vary widely in their capacities for thiamin synthesis. We use a transcriptomics approach to appraise the distribution of de novo synthesis and thiamin salvage pathways among organs of maize. We identify at least six developmental contexts in which metabolically active, non-photosynthetic organs exhibit low expression of one or both branches of the de novo thiamin biosynthetic pathway indicating a dependence on inter-cellular transport of thiamin and/or thiamin precursors. Neither the thiazole (THI4) nor pyrimidine (THIC) branches of the pathway are expressed in developing pollen implying a dependence on import of thiamin from surrounding floral and inflorescence organs. Consistent with that hypothesis, organs of the male inflorescence and flowers are shown to have high relative expression of the thiamin biosynthetic pathway and comparatively high thiamin contents. By contrast, divergent patterns of THIC and THI4 expression occur in the shoot apical meristem, embyro sac, embryo, endosperm, and root-tips suggesting that these sink organs acquire significant amounts of thiamin via salvage pathways. In the root and shoot meristems, expression of THIC in the absence of THI4 indicates a capacity for thiamin synthesis via salvage of thiazole, whereas the opposite pattern obtains in embryo and endosperm implying that seed storage organs are poised for pyrimidine salvage. Finally, stable isotope labeling experiments set an upper limit on the rate of de novo thiamin biosynthesis in maize leaf explants. Overall, the observed patterns of thiamin biosynthetic gene expression mirror the strategies for thiamin acquisition that have evolved in bacteria. PMID- 25136342 TI - Impaired clearance of apoptotic cells in chronic inflammatory diseases: therapeutic implications. AB - In healthy individuals, billions of cells die by apoptosis every day. Removal of the dead cells by phagocytosis (a process called efferocytosis) must be efficient to prevent secondary necrosis and the consequent release of pro-inflammatory cell contents that damages the tissue environment and provokes autoimmunity. In addition, detection and removal of apoptotic cells generally induces an anti inflammatory response. As a consequence improper clearance of apoptotic cells, being the result of either genetic anomalies and/or a persistent disease state, contributes to the establishment and progression of a number of human chronic inflammatory diseases such as autoimmune and neurological disorders, inflammatory lung diseases, obesity, type 2 diabetes, or atherosclerosis. During the past decade, our knowledge about the mechanism of efferocytosis has significantly increased, providing therapeutic targets through which impaired phagocytosis of apoptotic cells and the consequent inflammation could be influenced in these diseases. PMID- 25136346 TI - Capsicum chinensis L. growth and nutraceutical properties are enhanced by biostimulants in a long-term period: chemical and metabolomic approaches. AB - Two biostimulants, one derived from alfalfa plants (AH) and the other obtained from red grape (RG), were chemically characterized using enzyme linked immuno sorbent assays, Fourier transform infrared (FT-IR) and Raman spectroscopies. Two doses (50 and 100 mL L(-1) for RG, and 25 and 50 mL L(-1) for AH) of biostimulants were applied to Capsicum chinensis L. plants cultivated in pots inside a tunnel. The experimental design consisted of the factorial combination of treatment (no biostimulant, plus AH, plus RG) at three doses (zero, low, and high) and two time-course applications (at the second and fourth week after transplantation) and the effects were recorded at flowering and maturity. Both biostimulants contained different amounts of indoleacetic acid and isopentenyladenosine; the AH spectra exhibited amino acid functional groups in the peptidic structure, while the RG spectra showed the presence of polyphenols, such as resveratrol. These results revealed that at flowering, RG and AH increased the weights of fresh leaves and fruits and the number of green fruits, whereas at maturity, the biostimulants most affected the fresh weight and number of red fruits. At flowering, the leaves of the treated plants contained high amounts of epicatechin, ascorbic acid, quercetin, and dihydrocapsaicin. At maturity, the leaves of the treated plants exhibited elevated amounts of fructose, glucose, chlorogenic, and ferulic acids. Moreover, green fruits exhibited a high content of chlorogenic acid, p-hydroxybenzoic acid, p-coumaric acid and antioxidant activity, while both AH- and RG-treated red fruits were highly endowed in capsaicin. The (1)H high-resolution magic-angle spinning (HRMAS)-nuclear magnetic resonance (NMR) spectra of red fruits revealed that both products induced a high amount of NADP(+), whereas RG also increased glucose, fumarate, ascorbate, thymidine and high molecular weight species. Our results suggested that AH and RG promoted plant growth and the production of secondary metabolites, such as phenols. PMID- 25136348 TI - Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in S. cerevisiae. AB - A quantitative trait locus (QTL) in the nematode C. elegans, "lsq4," was recently implicated by mapping longevity genes. QTLs for lifespan and three stress resistance traits coincided within a span of <300 kbp, later narrowed to <200 kbp. A single gene in this interval is now shown to modulate all lsq4-associated traits. Full-genome analysis of transcript levels indicates that lsq4 contains a dimorphic gene governing the expression of many sperm-specific genes, suggesting an effect on spermatogenesis. Quantitative analysis of allele-specific transcripts encoded within the lsq4 interval revealed significant, 2- to 15-fold expression differences for 10 of 33 genes. Fourteen "dual-candidate" genes, implicated by both position and expression, were tested for RNA-interference effects on QTL-linked traits. In a strain carrying the shorter-lived allele, knockdown of rec-8 (encoding a meiotic cohesin) reduced its transcripts 4-fold, to a level similar to the longer-lived strain, while extending lifespan 25-26%, whether begun before fertilization or at maturity. The short-lived lsq4 allele also conferred sensitivity to oxidative and thermal stresses, and lower male frequency (reflecting X-chromosome non-disjunction), traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at <0.3% of its genome, derived no lifespan or stress survival benefit from rec-8 knockdown. We consider two possible explanations: high rec-8 expression may include increased "leaky" expression in mitotic cells, leading to deleterious destabilization of somatic genomes; or REC-8 may act entirely in germ-line meiotic cells to reduce aberrations such as non disjunction, thereby blunting a stress-resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741) by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, exemplifying antagonistic pleiotropy (opposing effects on lifespan vs. reproduction), and/or balancing selection wherein genomic disruption increases genetic variation under harsh conditions. PMID- 25136349 TI - The CNVrd2 package: measurement of copy number at complex loci using high throughput sequencing data. AB - Recent advances in high-throughout sequencing technologies have made it possible to accurately assign copy number (CN) at CN variable loci. However, current analytic methods often perform poorly in regions in which complex CN variation is observed. Here we report the development of a read depth-based approach, CNVrd2, for investigation of CN variation using high-throughput sequencing data. This methodology was developed using data from the 1000 Genomes Project from the CCL3L1 locus, and tested using data from the DEFB103A locus. In both cases, samples were selected for which paralog ratio test data were also available for comparison. The CNVrd2 method first uses observed read-count ratios to refine segmentation results in one population. Then a linear regression model is applied to adjust the results across multiple populations, in combination with a Bayesian normal mixture model to cluster segmentation scores into groups for individual CN counts. The performance of CNVrd2 was compared to that of two other read depth based methods (CNVnator, cn.mops) at the CCL3L1 and DEFB103A loci. The highest concordance with the paralog ratio test method was observed for CNVrd2 (77.8/90.4% for CNVrd2, 36.7/4.8% for cn.mops and 7.2/1% for CNVnator at CCL3L1 and DEF103A). CNVrd2 is available as an R package as part of the Bioconductor project: http://www.bioconductor.org/packages/release/bioc/html/CNVrd2.html. PMID- 25136347 TI - In silico analysis of protein Lys-N(??)-acetylation in plants. AB - Among post-translational modifications, there are some conceptual similarities between Lys-N(??)-acetylation and Ser/Thr/Tyr O-phosphorylation. Herein we present a bioinformatics-based overview of reversible protein Lys-acetylation, including some comparisons with reversible protein phosphorylation. The study of Lys-acetylation of plant proteins has lagged behind studies of mammalian and microbial cells; 1000s of acetylation sites have been identified in mammalian proteins compared with only hundreds of sites in plant proteins. While most previous emphasis was focused on post-translational modifications of histones, more recent studies have addressed metabolic regulation. Being directly coupled with cellular CoA/acetyl-CoA and NAD/NADH, reversible Lys-N(??)-acetylation has the potential to control, or contribute to control, of primary metabolism, signaling, and growth and development. PMID- 25136350 TI - Simple, standardized incorporation of genetic risk into non-genetic risk prediction tools for complex traits: coronary heart disease as an example. AB - PURPOSE: Genetic risk assessment is becoming an important component of clinical decision-making. Genetic Risk Scores (GRSs) allow the composite assessment of genetic risk in complex traits. A technically and clinically pertinent question is how to most easily and effectively combine a GRS with an assessment of clinical risk derived from established non-genetic risk factors as well as to clearly present this information to patient and health care providers. MATERIALS AND METHODS: We illustrate a means to combine a GRS with an independent assessment of clinical risk using a log-link function. We apply the method to the prediction of coronary heart disease (CHD) in the Atherosclerosis Risk in Communities (ARIC) cohort. We evaluate different constructions based on metrics of effect change, discrimination, and calibration. RESULTS: The addition of a GRS to a clinical risk score (CRS) improves both discrimination and calibration for CHD in ARIC. RESULTS are similar regardless of whether external vs. internal coefficients are used for the CRS, risk factor single nucleotide polymorphisms (SNPs) are included in the GRS, or subjects with diabetes at baseline are excluded. We outline how to report the construction and the performance of a GRS using our method and illustrate a means to present genetic risk information to subjects and/or their health care provider. CONCLUSION: The proposed method facilitates the standardized incorporation of a GRS in risk assessment. PMID- 25136351 TI - X-inactivation normalizes O-GlcNAc transferase levels and generates an O-GlcNAc depleted Barr body. AB - O-GlcNAc Transferase (OGT) catalyzes protein O-GlcNAcylation, an abundant and dynamic nuclear and cytosolic modification linked to epigenetic regulation of gene expression. The steady-state levels of O-GlcNAc are influenced by extracellular glucose concentrations suggesting that O-GlcNAcylation may serve as a metabolic sensor. Intriguingly, human OGT is located on the X-chromosome (Xq13) close to the X-inactivation center (XIC), suggesting that OGT levels may be controlled by dosage compensation. In human female cells, dosage compensation is accomplished by X-inactivation. Long noncoding RNAs and polycomb repression act together to produce an inactive X chromosome, or Barr body. Given that OGT has an established role in polycomb repression, it is uniquely poised to auto-regulate its own expression through X-inactivation. In this study, we examined OGT expression in male, female and triple-X female human fibroblasts, which differ in the number of inactive X chromosomes (Xi). We demonstrate that OGT is subjected to random X-inactivation in normal female and triple X cells to regulate OGT RNA levels. In addition, we used chromatin isolation by RNA purification (ChIRP) and immunolocalization to examine O-GlcNAc levels in the Xi/Barr body. Despite the established role of O-GlcNAc in polycomb repression, OGT and target proteins bearing O-GlcNAc are largely depleted from the highly condensed Barr body. Thus, while O-GlcNAc is abundantly present elsewhere in the nucleus, its absence from the Barr body suggests that the transcriptional quiescence of the Xi does not require OGT or O-GlcNAc. PMID- 25136352 TI - History of the discovery of a master locus producing piRNAs: the flamenco/COM locus in Drosophila melanogaster. AB - The discovery of transposable elements (TEs) in the 1950s by B. McClintock implied the existence of cellular regulatory systems controlling TE activity. The discovery of flamenco (flam) an heterochromatic locus from Drosophila melanogaster and its ability to survey several TEs such as gypsy, ZAM, and Idefix contributed to peer deeply into the mechanisms of the genetic and epigenetic regulation of TEs. flam was the first cluster producing small RNAs to be discovered long before RNAi pathways were identified in 1998. As a result of the detailed genetic analyses performed by certain laboratories and of the sophisticated genetic tools they developed, this locus has played a major role in our understanding of piRNA mediated TE repression in animals. Here we review the first discovery of this locus and retrace decades of studies that led to our current understanding of the relationship between genomes and their TE targets. PMID- 25136354 TI - Viper bites complicate chronic agrochemical nephropathy in rural Sri Lanka. AB - Snakebite is a common occupational health hazard among Sri Lankan agricultural workers, particularly in the North Central Province. Viperine snakes, mainly Russell's viper envenomation, frequently lead to acute renal failure. During the last two decades, an agrochemical nephropathy, a chronic tubulointerstitial disease has rapidly spread over this area leading to high morbidity and mortality. Most of the epidemiological characteristics of these two conditions overlap, increasing the chances of co-occurrence. Herein, we describe four representative cases of viperine snakebites leading to variable clinical presentations, in patients with chronic agrochemical nephropathy, including two patients presented with acute and delayed anuria. These cases suggest the possibility of unusual manifestations of snakebite in patients with Sri Lankan agrochemical nephropathy, of which the clinicians should be aware. It could be postulated that the existing scenario in the Central America could also lead to similar clinical presentations. PMID- 25136355 TI - Automated White Matter Hyperintensity Detection in Multiple Sclerosis Using 3D T2 FLAIR. AB - White matter hyperintensities (WMH) seen on T2WI are a hallmark of multiple sclerosis (MS) as it indicates inflammation associated with the disease. Automatic detection of the WMH can be valuable in diagnosing and monitoring of treatment effectiveness. T2 fluid attenuated inversion recovery (FLAIR) MR images provided good contrast between the lesions and other tissue; however the signal intensity of gray matter tissue was close to the lesions in FLAIR images that may cause more false positives in the segment result. We developed and evaluated a tool for automated WMH detection only using high resolution 3D T2 fluid attenuated inversion recovery (FLAIR) MR images. We use a high spatial frequency suppression method to reduce the gray matter area signal intensity. We evaluate our method in 26 MS patients and 26 age matched health controls. The data from the automated algorithm showed good agreement with that from the manual segmentation. The linear correlation between these two approaches in comparing WMH volumes was found to be Y = 1.04X + 1.74 (R (2) = 0.96). The automated algorithm estimates the number, volume, and category of WMH. PMID- 25136353 TI - Genetic factors and manganese-induced neurotoxicity. AB - Manganese (Mn), is a trace metal required for normal physiological processes in humans. Mn levels are tightly regulated, as high levels of Mn result in accumulation in the brain and cause a neurological disease known as manganism. Manganism shares many similarities with Parkinson's disease (PD), both at the physiological level and the cellular level. Exposure to high Mn-containing environments increases the risk of developing manganism. Mn is absorbed primarily through the intestine and then released in the blood. Excessive Mn is secreted in the bile and excreted in feces. Mn enters and exits cells through a number of non specific importers localized on the cell membrane. Mutations in one of the Mn exporters, SLC30A10 (solute carrier family 30, member 10), result in Mn induced toxicity with liver impairments and neurological dysfunction. Four PD genes have been identified in connection to regulation of Mn toxicity, shedding new light on potential links between manganism and PD. PMID- 25136358 TI - An ICT-Based Diabetes Management System Tested for Health Care Delivery in the African Context. AB - The demand for new healthcare services is growing rapidly. Improving accessibility of the African population to diabetes care seems to be a big challenge in most countries where the number of care centers and medical staff is reduced. Information and communication technologies (ICT) have great potential to address some of these challenges faced by several countries in providing accessible, cost-effective, and high-quality health care services. This paper presents the Mobil Diab system which is a telemedical approach proposed for the management of long-term diseases. The system applies modern mobile and web technologies which overcome geographical barriers, and increase access to health care services. The idea of the system is to involve patients in the therapy process and motivate them for an active participation. For validation of the system in African context, a trial was conducted in the Democratic Republic of Congo. 40 Subjects with diabetes divided randomly into control and intervention groups were included in the test. Results show that Mobil Diab is suitable for African countries and presents a number of benefits for the population and public health care system. It improves clinical management and delivery of diabetes care services by enhancing access, quality, motivation, reassurance, efficiency, and cost-effectiveness. PMID- 25136357 TI - Haematuria: an imaging guide. AB - This paper discusses the current status of imaging in the investigation of patients with haematuria. The physician must rationalize imaging so that serious causes such as malignancy are promptly diagnosed while at the same time not exposing patients to unnecessary investigations. There is currently no universal agreement about the optimal imaging work up of haematuria. The choice of modality to image the urinary tract will depend on individual patient factors such as age, the presence of risk factors for malignancy, renal function, a history of calculus disease and pregnancy, and other factors, such as local policy and practice, cost effectiveness and availability of resources. The role of all modalities, including conventional radiography, intravenous urography/excretory urography, ultrasonography, retrograde pyelography, multidetector computed tomography urography (MDCTU), and magnetic resonance urography, is discussed. This paper highlights the pivotal role of MDCTU in the imaging of the patient with haematuria and discusses issues specific to this modality including protocol design, imaging of the urothelium, and radiation dose. Examination protocols should be tailored to the patient while all the while optimizing radiation dose. PMID- 25136356 TI - Targeting angiogenesis and tumor microenvironment in metastatic colorectal cancer: role of aflibercept. AB - In the last decades, we have progressively observed an improvement in therapeutic options for metastatic colorectal cancer (mCRC) treatment with a progressive prolongation of survival. mCRC prognosis still remains poor with low percentage of 5-year survival. Targeted agents have improved results obtained with standard chemotherapy. Angiogenesis plays a crucial role in colorectal cancer growth, proliferation, and metastasization and it has been investigated as a potential target for mCRC treatment. Accordingly, novel antiangiogenic targeted agents bevacizumab, regorafenib, and aflibercept have been approved for mCRC treatment as the result of several phase III randomized trials. The development of a tumor permissive microenvironment via the aberrant expression by tumor cells of paracrine factors alters the tumor-stroma interactions inducing an expansion of proangiogenic signals. Recently, the VELOUR study showed that addition of aflibercept to FOLFIRI regimen as a second-line therapy for mCRC improved significantly OS, PFS, and RR. This molecule represents a valid second-line therapeutic option and its peculiar ability to interfere with placental growth factor (PlGF)/vascular endothelial growth factor receptor 1 (VEGFR1) axis makes it effective in targeting angiogenesis, inflammatory cells and in overcoming resistances to anti-angiogenic first-line treatment. Here, we discuss about Aflibercept peculiar ability to interfere with tumor microenvironment and angiogenic pathway. PMID- 25136359 TI - Physical Activity, Physical Performance, and Biological Markers of Health among Sedentary Older Latinos. AB - Background. Physical activity is associated with better physical health, possibly by changing biological markers of health such as waist circumference and inflammation, but these relationships are unclear and even less understood among older Latinos-a group with high rates of sedentary lifestyle. Methods. Participants were 120 sedentary older Latino adults from senior centers. Community-partnered research methods were used to recruit participants. Inflammatory (C-reactive protein) and metabolic markers of health (waist circumference, HDL-cholesterol, triglycerides, insulin, and glucose), physical activity (Yale physical activity survey), and physical performance (short physical performance NIA battery) were measured at baseline and 6-month followup. Results. Eighty percent of the sample was female. In final adjusted cross sectional models, better physical activity indices were associated with faster gait speed (P < 0.05). In adjusted longitudinal analyses, change in self-reported physical activity level correlated inversely with change in CRP (beta = -0.05; P = 0.03) and change in waist circumference (beta = -0.16; P = 0.02). Biological markers of health did not mediate the relationship between physical activity and physical performance. Conclusion. In this community-partnered study, higher physical activity was associated with better physical performance in cross sectional analyses. In longitudinal analysis, increased physical activity was associated with improvements in some metabolic and inflammatory markers of health. PMID- 25136360 TI - Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine. AB - Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and caftaric acids are the major dietary polyphenols present in various foods. The aim of this study was to evaluate the protective role of chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine in rats. Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10 mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected (i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively, one day before methamphetamine injections. Methamphetamine increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also, malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide levels were increased while methamphetamine induced a significant decrease in serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin, norepinephrine and dopamine, blood and liver superoxide dismutase, and glutathione peroxidase levels. Chlorogenic and caftaric acids prior to methamphetamine injections restored all the above parameters to normal values. In conclusion, chlorogenic and caftaric acids before methamphetamine injections prevented liver toxicity and oxidative stress where chlorogenic acid was more effective. PMID- 25136361 TI - Micro- and Macroelemental Composition and Safety Evaluation of the Nutraceutical Moringa oleifera Leaves. AB - Moringa oleifera is a multipurpose plant used in Ghana and most parts of Africa. Its high mineral, protein, and vitamins content has enabled its use as a nutraceutical and panacea for various diseases. This study aimed at measuring the micro- and macroelements content of dried Moringa oleifera leaves using energy dispersive X-ray fluorescence spectroscopic (EDXRF) and assessing its toxicological effect in rats. Acute toxicity (5000 mg/kg) and a subacute toxicity studies of the leaf (40 mg/kg to 1000 mg/kg) extract were conducted in rats. Blood samples were assessed for biochemical and haematological parameters. Results showed significant levels of thirty-five (35) elements (14 macroelements and 21 microelements) in M. oleifera extract. There were no observed overt adverse reactions in the acute and subacute studies. Although there were observed elevations in liver enzymes ALT and ALP (P < 0.001) and lower creatinine levels in the extract treated groups, no adverse histopathological findings were found. Moringa oleifera dried leaf extract may, therefore, be reasonably safe for consumption. However, the consumption of Moringa oleifera leaves should not exceed a maximum of 70 grams per day to prevent cumulative toxicity of these essential elements over long periods. PMID- 25136362 TI - The TG/HDL-C Ratio Might Be a Surrogate for Insulin Resistance in Chinese Nonobese Women. AB - Obejective. To examine the discriminatory power of triglyceride (TG) and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) for insulin resistance (IR) in a normoglycaemic Chinese population. Methods. The data were collected from 711 individuals. The normoglycaemic individuals were eventually included in the study (n = 533, age: 62.8 +/- 6.6 years, male: 56.8%), who were with a fasting plasma glucose < 6.1 mmol/L and without a history of diabetes. IR was defined as the upper quintile (>=1.6) of homeostasis model assessment of IR. Area under the receiver operating characteristic curve (AROC) was used to examine the discriminatory power. Results. The discriminatory power of TG/HDL-C for IR was acceptable in women with a BMI < 24 kg/m(2) or waist circumference < 80 cm (AROCs: 0.718 and 0.713, resp.); however, the discriminatory power was not acceptable in the obese women. TG/HDL-C was not an acceptable marker of IR in men. The discriminatory power of TG for IR was not acceptable in both men and women. Conclusions. The discriminatory power of TG/HDL-C for IR differs by gender and obesity index in the normoglycaemic Chinese population, and TG/HDL-C could discriminate IR in the nonobese and normoglycaemic women. PMID- 25136363 TI - Leptin effects on the regenerative capacity of human periodontal cells. AB - Obesity is increasing throughout the globe and characterized by excess adipose tissue, which represents a complex endocrine organ. Adipose tissue secrets bioactive molecules called adipokines, which act at endocrine, paracrine, and autocrine levels. Obesity has recently been shown to be associated with periodontitis, a disease characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium, and also with compromised periodontal healing. Although the underlying mechanisms for these associations are not clear yet, increased levels of proinflammatory adipokines, such as leptin, as found in obese individuals, might be a critical pathomechanistic link. The objective of this study was to examine the impact of leptin on the regenerative capacity of human periodontal ligament (PDL) cells and also to study the local leptin production by these cells. Leptin caused a significant downregulation of growth (TGFbeta1, and VEGFA) and transcription (RUNX2) factors as well as matrix molecules (collagen, and periostin) and inhibited SMAD signaling under regenerative conditions. Moreover, the local expression of leptin and its full-length receptor was significantly downregulated by inflammatory, microbial, and biomechanical signals. This study demonstrates that the hormone leptin negatively interferes with the regenerative capacity of PDL cells, suggesting leptin as a pathomechanistic link between obesity and compromised periodontal healing. PMID- 25136364 TI - Cannabinoid receptor 1 gene polymorphisms and nonalcoholic Fatty liver disease in women with polycystic ovary syndrome and in healthy controls. AB - Context. Polycystic ovary syndrome (PCOS) is frequently associated with nonalcoholic fatty liver disease (NAFLD). The endocannabinoid system may play a crucial role in the pathogenesis of NAFLD. Polymorphism of the cannabinoid receptor 1 gene (CNR1) may be responsible for individual susceptibility to obesity and related conditions. Objective. To determine the role of genetic variants of CNR1 in the etiopathology of NAFLD in women with PCOS. Design and Setting. Our department (a tertiary referral center) conducted a cross-sectional, case-controlled study. Subjects. 173 women with PCOS (aged 20-35) and 125 healthy, age- and weight-matched controls were studied. Methods. Hepatic steatosis was assessed by ultrasound evaluation. Single nucleotide polymorphisms of CNR1 (rs806368, rs12720071, rs1049353, rs806381, rs10485170, rs6454674) were genotyped. Results. Frequency of the G allele of rs806381 (P < 0.025) and the GG genotype of rs10485170 (P < 0.03) was significantly higher in women with PCOS and NAFLD than in PCOS women without NAFLD. Frequency of the TT genotype of rs6454674 was higher in PCOS women with NAFLD (not significantly, P = 0.059). In multivariate stepwise regression, allele G of rs806381 was associated with PCOS + NAFLD phenotype. Conclusion. Our preliminary results suggest the potential role of CNR1 polymorphisms in the etiology of NAFLD, especially in PCOS women. PMID- 25136366 TI - Association between Serum Uric Acid Level and Metabolic Syndrome and Its Sex Difference in a Chinese Community Elderly Population. AB - Objective. This study aimed to evaluate the association between serum uric acid (SUA) levels within a normal to high range and the risk of metabolic syndrome (MetS) among community elderly and explore the sex difference. Design and Methods. A cross-sectional study was conducted in a representative urban area of Beijing between 2009 and 2010. A two-stage stratified clustering sampling method was used and 2102 elderly participants were included. Results. The prevalence of hyperuricemia and MetS was 16.7% and 59.1%, respectively. There was a strong association between hyperuricemia and four components of MetS in women and three components in men. Multiple logistic regression analysis showed ORs of hyperuricemia for MetS were 1.67 (95% CI: 1.11-2.50) in men and 2.73 (95% CI: 1.81-4.11) in women. Even in the normal range, the ORs for MetS increased gradually according to SUA levels. MetS component number also showed an increasing trend across SUA quartile in both sexes (P for trend < 0.01). Conclusion. This study suggests that higher SUA levels, even in the normal range, are positively associated with MetS among Chinese community elderly, and the association is stronger in women than men. Physicians should recognize MetS as a frequent comorbidity of hyperuricemia and take early action to prevent subsequent disease burden. PMID- 25136365 TI - Coronary Heart Disease in Postmenopausal Women with Type II Diabetes Mellitus and the Impact of Estrogen Replacement Therapy: A Narrative Review. AB - Coronary heart disease is the main cause of death in postmenopausal women (PMW); moreover its mortality exceeds those for breast cancer in women at all ages. Type II diabetes mellitus is a major cardiovascular risk factor and there is some evidence that the risk conferred by diabetes is greater in women than in men. It was established that the deficiency of endogenous estrogens promotes the atherosclerosis process. However, the impact of estrogen replacement therapy (ERT) on cardiovascular prevention remains controversial. Some authors strongly recommend it, whereas others revealed a concerning trend toward harm. This review tries to underlines the different components of cardiovascular risk in diabetic PMW and to define the place of ERT. PMID- 25136367 TI - The Need for Orthodontic Treatment among Vietnamese School Children and Young Adults. AB - Objective. The aim of this study was to evaluate the need for orthodontic treatment among 12-year-old school children and 18-year-olds from Da Nang, Vietnam. Basic Research Design. A random representative sample of 200 12-year-old children from primary schools in Da Nang city was gathered. In addition, 200 18 year-old students were randomly selected from among the 4000 students studying at Da Nang University of Medical Technology and Pharmacy, Vietnam. All the subjects were evaluated according to Angle's molar relationship, the presence of malocclusion, and the components of the Index of Orthodontic Treatment Need (Dental Health Component, DHC, and Aesthetic Component, AC). Results. The DHC of index of orthodontic treatment need (IOTN) for 12-year-olds was in 60% of cases no or little, in 21% of cases moderate, and in 19% of cases definitive, while the prevalence of moderate and definitive need for treatment among the 18-year-olds was 24% and 30.5%, respectively. The prevalence of class III malocclusion, contact point displacement, and crossbite was higher in 18-year-olds than among the 12-year-olds, while the prevalence of increased overjet and increased overbite had decreased in 18-year-olds compared to the group of 12-year-olds. Conclusions. There is a strong need for orthodontic treatment in Vietnam's population. The need for orthodontic treatment was determined by contact point displacement, crossbite, increased overjet, and increased overbite. PMID- 25136368 TI - Effect of recycling protocol on mechanical strength of used mini-implants. AB - Purpose. This study evaluated the influence of recycling process on the torsional strength of mini-implants. Materials and Methods. Two hundred mini-implants were divided into 4 groups with 50 screws equally distributed in five diameters (1.3 to 1.7 mm): control group (CG): unused mini-implants, G1: mini-implants inserted in pig iliac bone and removed, G2: same protocol of group 1 followed by sonication for cleaning and autoclave sterilization, and G3: same insertion protocol of group 1 followed by sonication for cleaning before and after sandblasting (Al2O3-90 u) and autoclave sterilization. G2 and G3 mini-implants were weighed after recycling process to evaluate weight loss (W). All the screws were broken to determine the fracture torque (FT). The influence of recycling process on FT and W was evaluated by ANOVA, Mann-Whitney, and multiple linear regression analysis. Results. FT was not influenced by recycling protocols even when sandblasting was added. Sandblasting caused weight loss due to abrasive mechanical stripping of screw surface. Screw diameter was the only variable that affected FT. Conclusions. Torsional strengths of screws that underwent the recycling protocols were not changed. Thus, screw diameter choice can be a more critical step to avoid screw fracture than recycling decision. PMID- 25136370 TI - Efficacy of topical mesenchymal stem cell therapy in the treatment of experimental dry eye syndrome model. AB - Purpose. The current study was set out to address the therapeutic efficacy of topically applied mesenchymal stem cells (MSCs) on dry eye syndrome (DES) induced by benzalkonium chloride (BAC) in rats. Methods. Rats were divided into two groups just after establishment of DES. Eye drops containing either bromodeoxyuridine labeled MSCs (n = 9) or phosphate buffer solution (n = 7) were topically applied once daily for one week. Schirmer test, break-up time score, ocular surface evaluation tests, and corneal inflammatory index scoring tests were applied to all rats at baseline and after treatment. All rats were sacrificed after one week for histological and electron microscopic analysis. Results. Mean aqueous tear volume and tear film stability were significantly increased in rats treated with MSCs (P < 0.05). Infiltration of bromodeoxyuridine labeled MSCs into the meibomian glands and conjunctival epithelium was observed in MSCs treated rats. Increased number of secretory granules and number of goblet cells were observed in MSCs treated rats. Conclusion. Topical application of MSCs could be a safe and effective method for the treatment of DES and could potentially be used for further clinical research studies. PMID- 25136369 TI - Early prediction of preeclampsia. AB - Effective screening for the development of early onset preeclampsia (PE) can be provided in the first-trimester of pregnancy. Screening by a combination of maternal risk factors, uterine artery Doppler, mean arterial pressure, maternal serum pregnancy-associated plasma protein-A, and placental growth factor can identify about 95% of cases of early onset PE for a false-positive rate of 10%. PMID- 25136371 TI - Determination of lead, cations, and anions concentration in indoor and outdoor air at the primary schools in Kuala Lumpur. AB - This study was carried out to determine the concentration of lead (Pb), anions, and cations at six primary schools located around Kuala Lumpur. Low volume sampler (MiniVol PM10) was used to collect the suspended particulates in indoor and outdoor air. Results showed that the concentration of Pb in indoor air was in the range of 5.18 +/- 1.08 MUg/g-7.01 +/- 0.08 MUg/g. All the concentrations of Pb in indoor air were higher than in outdoor air at all sampling stations. The concentrations of cations and anions were higher in outdoor air than in indoor air. The concentration of Ca(2+) (39.51 +/- 5.01 mg/g-65.13 +/- 9.42 mg/g) was the highest because the cation existed naturally in soil dusts, while the concentrations of NO3 (-) and SO4 (2-) were higher in outdoor air because there were more sources of exposure for anions in outdoor air, such as highly congested traffic and motor vehicles emissions. In comparison, the concentration of NO3 (-) (29.72 +/- 0.31 MUg/g-32.00 +/- 0.75 MUg/g) was slightly higher than SO4 (2-). The concentrations of most of the parameters in this study, such as Mg(2+), Ca(2+), NO3 (-), SO4 (2-), and Pb(2+), were higher in outdoor air than in indoor air at all sampling stations. PMID- 25136372 TI - Treatment of acute lymphoblastic leukemia from traditional chinese medicine. AB - Acute lymphoblastic leukemia (ALL) is a cancer that immature white blood cells continuously overproduce in the bone marrow. These cells crowd out normal cells in the bone marrow bringing damage and death. Methotrexate (MTX) is a drug used in the treatment of various cancer and autoimmune diseases. In particular, for the treatment of childhood acute lymphoblastic leukemia, it had significant effect. MTX competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis so as to inhibit purine synthesis. In addition, its downstream metabolite methotrexate polyglutamates (MTX-PGs) inhibit the thymidylate synthase (TS). Therefore, MTX can inhibit the synthesis of DNA. However, MTX has cytotoxicity and neurotoxin may cause multiple organ injury and is potentially lethal. Thus, the lower toxicity drugs are necessary to be developed. Recently, diseases treatments with Traditional Chinese Medicine (TCM) as complements are getting more and more attention. In this study, we attempted to discover the compounds with drug-like potential for ALL treatment from the components in TCM. We applied virtual screen and QSAR models based on structure-based and ligand-based studies to identify the potential TCM component compounds. Our results show that the TCM compounds adenosine triphosphate, manninotriose, raffinose, and stachyose could have potential to improve the side effects of MTX for ALL treatment. PMID- 25136373 TI - St. John's Wort Has Metabolically Favorable Effects on Adipocytes In Vivo. AB - In addition to serving as a storage site for reserve energy, adipocytes play a critical role in whole-body insulin sensitivity and glucose metabolism. St. John's Wort (SJW) is a botanical supplement widely used as an over-the-counter treatment of depression and a variety of other conditions associated with anxiety and nerve pain. Previous studies in our laboratory demonstrated that SJW inhibits insulin-stimulated glucose uptake and adipocyte differentiation in cultured murine and mature human adipocytes. To investigate the effects of SJW on adipocyte function in vivo, we utilized C57BL/6J mice. In our studies, mice were administered SJW extract (200 mg/kg) once daily by gavage for two weeks. In contrast to our in vitro studies, mice treated with SJW extract showed increased levels of adiponectin in white adipose tissue in a depot specific manner (P < 0.01). SJW also exerted an insulin-sensitizing effect as indicated by a significant increase in insulin-stimulated Akt serine phosphorylation in epididymal white adipose tissue (P < 0.01). Food intake, body weight, fasting blood glucose, and fasting insulin did not differ between the two groups. These results are important as they indicate that SJW does not promote metabolic dysfunction in adipose tissue in vivo. PMID- 25136374 TI - Anti-trichophyton activity of protocatechuates and their synergism with fluconazole. AB - Dermatophytosis and superficial mycosis are a major global public health problem that affects 20-25% of the world's population. The increase in fungal resistance to the commercially available antifungal agents, in conjunction with the limited spectrum of action of such drugs, emphasises the need to develop new antifungal agents. Natural products are attractive prototypes for antifungal agents due to their broad spectrum of biological activities. This study aimed to verify the antifungal activity of protocatechuic acid, 3,4-diacetoxybenzoic, and fourteen alkyl protocatechuates (3,4-dihydroxybenzoates) against Trichophyton rubrum and Trichophyton mentagrophytes and to further assess their activities when combined with fluconazole. Susceptibility and synergism assays were conducted as described in M38-A2 (CLSI), with modifications. Three strains of Trichophyton rubrum and three strains of Trichophyton mentagrophytes were used in this work. The pentyl, hexyl, heptyl, octyl, nonyl, and decyl protocatechuates showed great fungicidal effects, with minimum inhibitory concentration (MIC) values ranging from 0.97 to 7.8 mg/L. Heptyl showed a synergistic activity (FIC index = 0.49), reducing the MIC of fluconazole by fourfold. All substances tested were safe, especially the hexyl, heptyl, octyl, and nonyl compounds, all of which showed a high selectivity index, particularly in combination with fluconazole. These ester associations with fluconazole may represent a promising source of prototypes in the search for anti-Trichophyton therapeutic agents. PMID- 25136375 TI - Acupuncture Point Laterality: Investigation of Acute Effects of Quchi (LI11) in Patients with Hypertension Using Heart Rate Variability. AB - Hypertension is one of the major risk factors for cardiovascular disease worldwide. Over 70% of the patients use antihypertensive drugs, so nonpharmacological treatments in addition to the medication are important. Our goal was to investigate acupuncture treatment on the Quchi acupoint using heart rate (HR) and heart rate variability (HRV) and to find out whether there is a laterality in acute effects. Sixty hypertensive patients (36 female, 24 male; mean age +/- SD 55.8 +/- 9.7 years) were randomly assigned to two manual needle acupuncture groups (group A: left Quchi (LI11) acupoint, group B: right Quchi acupoint). There was a significant (P < 0.05) decrease in HR immediately after inserting and stimulating the needle at the left and the right Quchi acupuncture point. In contrast, total HRV increased immediately after inserting the needle, but this increase was significant only towards the end of the stimulation phase and after removing the needle. There were some differences between stimulation of the left and right Quchi acupoint, but they remained insignificant. This study provides evidence that there is a beneficial effect on heart rate variability in patients with hypertension and that there are some effects of laterality of the acupoint Quchi. PMID- 25136378 TI - Systems and synthetic biology approaches to cell division. AB - Cells proliferate by division into similar daughter cells, a process that lies at the heart of cell biology. Extensive research on cell division has led to the identification of the many components and control elements of the molecular machinery underlying cellular division. Here we provide a brief review of prokaryotic and eukaryotic cell division and emphasize how new approaches such as systems and synthetic biology can provide valuable new insight. PMID- 25136376 TI - Mouse models of the fragile X premutation and fragile X-associated tremor/ataxia syndrome. AB - Carriers of the fragile X premutation (FPM) have CGG trinucleotide repeat expansions of between 55 and 200 in the 5'-UTR of FMR1, compared to a CGG repeat length of between 5 and 54 for the general population. Carriers were once thought to be without symptoms, but it is now recognized that they can develop a variety of early neurological symptoms as well as being at risk for developing the late onset neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Several mouse models have contributed to our understanding of FPM and FXTAS, and findings from studies using these models are summarized here. This review also discusses how this information is improving our understanding of the molecular and cellular abnormalities that contribute to neurobehavioral features seen in some FPM carriers and in patients with FXTAS. Mouse models show much of the pathology seen in FPM carriers and in individuals with FXTAS, including the presence of elevated levels of Fmr1 mRNA, decreased levels of fragile X mental retardation protein, and ubiquitin-positive intranuclear inclusions. Abnormalities in dendritic spine morphology in several brain regions are associated with neurocognitive deficits in spatial and temporal memory processes, impaired motor performance, and altered anxiety. In vitro studies have identified altered dendritic and synaptic architecture associated with abnormal Ca(2+) dynamics and electrical network activity. FPM mice have been particularly useful in understanding the roles of Fmr1 mRNA, fragile X mental retardation protein, and translation of a potentially toxic polyglycine peptide in pathology. Finally, the potential for using these and emerging mouse models for preclinical development of therapies to improve neurological function in FXTAS is considered. PMID- 25136377 TI - The cognitive neuropsychological phenotype of carriers of the FMR1 premutation. AB - The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting a subset of carriers of the FMR1 (fragile X mental retardation 1) premutation. Penetrance and expression appear to be significantly higher in males than females. Although the most obvious aspect of the phenotype is the movement disorder that gives FXTAS its name, the disorder is also accompanied by progressive cognitive impairment. In this review, we address the cognitive neuropsychological and neurophysiological phenotype for males and females with FXTAS, and for male and female unaffected carriers. Despite differences in penetrance and expression, the cognitive features of the disorder appear similar for both genders, with impairment of executive functioning, working memory, and information processing the most prominent. Deficits in these functional systems may be largely responsible for impairment on other measures, including tests of general intelligence and declarative learning. FXTAS is to a large extent a white matter disease, and the cognitive phenotypes observed are consistent with what some have described as white matter dementia, in contrast to the impaired cortical functioning more characteristic of Alzheimer's disease and related disorders. Although some degree of impaired executive functioning appears to be ubiquitous among persons with FXTAS, the data suggest that only a subset of unaffected carriers of the premutation - both female and male - demonstrate such deficits, which typically are mild. The best-studied phenotype is that of males with FXTAS. The manifestations of cognitive impairment among asymptomatic male carriers, and among women with and without FXTAS, are less well understood, but have come under increased scrutiny. PMID- 25136379 TI - Swinging a sword: how microtubules search for their targets. AB - The cell interior is in constant movement, which is to a large extent determined by microtubules, thin and long filaments that permeate the cytoplasm. To move large objects, microtubules need to connect them to the site of their destination. For example, during cell division, microtubules connect chromosomes with the spindle poles via kinetochores, protein complexes on the chromosomes. A general question is how microtubules, while being bound to one structure, find the target that needs to be connected to this structure. Here we review the mechanisms of how microtubules search for kinetochores, with emphasis on the recently discovered microtubule feature to explore space by pivoting around the spindle pole. In addition to accelerating the search for kinetochores, pivoting helps the microtubules to search for cortical anchors, as well as to self organize into parallel arrays and asters to target specific regions of the cell. Thus, microtubule pivoting constitutes a mechanism by which they locate targets in different cellular contexts. PMID- 25136380 TI - Microtubule networks for plant cell division. AB - During cytokinesis the cytoplasm of a cell is divided to form two daughter cells. In animal cells, the existing plasma membrane is first constricted and then abscised to generate two individual plasma membranes. Plant cells on the other hand divide by forming an interior dividing wall, the so-called cell plate, which is constructed by localized deposition of membrane and cell wall material. Construction starts in the centre of the cell at the locus of the mitotic spindle and continues radially towards the existing plasma membrane. Finally the membrane of the cell plate and plasma membrane fuse to form two individual plasma membranes. Two microtubule-based cytoskeletal networks, the phragmoplast and the pre-prophase band (PPB), jointly control cytokinesis in plants. The bipolar microtubule array of the phragmoplast regulates cell plate deposition towards a cortical position that is templated by the ring-shaped microtubule array of the PPB. In contrast to most animal cells, plants do not use centrosomes as foci of microtubule growth initiation. Instead, plant microtubule networks are striking examples of self-organizing systems that emerge from physically constrained interactions of dispersed microtubules. Here we will discuss how microtubule based activities including growth, shrinkage, severing, sliding, nucleation and bundling interrelate to jointly generate the required ordered structures. Evidence mounts that adapter proteins sense the local geometry of microtubules to locally modulate the activity of proteins involved in microtubule growth regulation and severing. Many of the proteins and mechanisms involved have roles in other microtubule assemblies as well, bestowing broader relevance to insights gained from plants. PMID- 25136383 TI - Mechanisms of cell division as regulators of acute immune response. AB - The acute adaptive immune response is complex, proceeding through phases of activation of quiescent lymphocytes, rapid expansion by cell division and cell differentiation, cessation of division and eventual death of greater than 95 % of the newly generated population. Control of the response is not central but appears to operate as a distributed process where global patterns reliably emerge as a result of collective behaviour of a large number of autonomous cells. In this review, we highlight evidence that competing intracellular timed processes underlie the distribution of individual fates and control cell proliferation, cessation and loss. These principles can be captured in a mathematical model to illustrate consistency with previously published experimentally observed data. PMID- 25136381 TI - When genome integrity and cell cycle decisions collide: roles of polo kinases in cellular adaptation to DNA damage. AB - The drive to proliferate and the need to maintain genome integrity are two of the most powerful forces acting on biological systems. When these forces enter in conflict, such as in the case of cells experiencing DNA damage, feedback mechanisms are activated to ensure that cellular proliferation is stopped and no further damage is introduced while cells repair their chromosomal lesions. In this circumstance, the DNA damage response dominates over the biological drive to proliferate, and may even result in programmed cell death if the damage cannot be repaired efficiently. Interestingly, the drive to proliferate can under specific conditions overcome the DNA damage response and lead to a reactivation of the proliferative program in checkpoint-arrested cells. This phenomenon is known as adaptation to DNA damage and is observed in all eukaryotic species where the process has been studied, including normal and cancer cells in humans. Polo-like kinases (PLKs) are critical regulators of the adaptation response to DNA damage and they play key roles at the interface of cell cycle and checkpoint-related decisions in cells. Here, we review recent progress in defining the specific roles of PLKs in the adaptation process and how this conserved family of eukaryotic kinases can integrate the fundamental need to preserve genomic integrity with effective cellular proliferation. PMID- 25136384 TI - Experiments inside a box lead to out-of-the-box ideas on cellular organization. AB - Microtubules are biopolymers that assemble from tubulin dimers into hollow tubes and play an important role in cellular organization. Their fascinating properties and variety of functions, like for example chromosome segregation, sperm propagation and polarity establishment, have made them a popular subject of study. In this perspective I focus on the contribution of minimal in vitro systems to our understanding of microtubule organization within the physical confinement of a cell. PMID- 25136382 TI - Role and regulation of kinesin-8 motors through the cell cycle. AB - Members of the kinesin-8 motor family play a central role in controlling microtubule length throughout the eukaryotic cell cycle. Inactivation of kinesin 8 causes defects in cell polarity during interphase and astral and mitotic spindle length, metaphase chromosome alignment, timing of anaphase onset and accuracy of chromosome segregation. Although the biophysical mechanism by which kinesin-8 molecules influence microtubule dynamics has been studied extensively in a variety of species, a consensus view has yet to emerge. One reason for this might be that some members of the kinesin-8 family can associate to other microtubule-associated proteins, cell cycle regulatory proteins and other kinesin family members. In this review we consider how cell cycle specific modification and its association to other regulatory proteins may modulate the function of kinesin-8 to enable it to function as a master regulator of microtubule dynamics. PMID- 25136385 TI - Getting into shape: How do rod-like bacteria control their geometry? AB - Rod-like bacteria maintain their cylindrical shapes with remarkable precision during growth. However, they are also capable to adapt their shapes to external forces and constraints, for example by growing into narrow or curved confinements. Despite being one of the simplest morphologies, we are still far from a full understanding of how shape is robustly regulated, and how bacteria obtain their near-perfect cylindrical shapes with excellent precision. However, recent experimental and theoretical findings suggest that cell-wall geometry and mechanical stress play important roles in regulating cell shape in rod-like bacteria. We review our current understanding of the cell wall architecture and the growth dynamics, and discuss possible candidates for regulatory cues of shape regulation in the absence or presence of external constraints. Finally, we suggest further future experimental and theoretical directions which may help to shed light on this fundamental problem. PMID- 25136386 TI - Toward the assembly of a minimal divisome. AB - The construction of an irreducible minimal cell having all essential attributes of a living system is one of the biggest challenges facing synthetic biology. One ubiquitous task accomplished by any living systems is the division of the cell envelope. Hence, the assembly of an elementary, albeit sufficient, molecular machinery that supports compartment division, is a crucial step towards the realization of self-reproducing artificial cells. Looking backward to the molecular nature of possible ancestral, supposedly more rudimentary, cell division systems may help to identify a minimal divisome. In light of a possible evolutionary pathway of division mechanisms from simple lipid vesicles toward modern life, we define two approaches for recapitulating division in primitive cells: the membrane deforming protein route and the lipid biosynthesis route. Having identified possible proteins and working mechanisms participating in membrane shape alteration, we then discuss how they could be integrated into the construction framework of a programmable minimal cell relying on gene expression inside liposomes. The protein synthesis using recombinant elements (PURE) system, a reconstituted minimal gene expression system, is conceivably the most versatile synthesis platform. As a first step towards the de novo synthesis of a divisome, we showed that the N-BAR domain protein produced from its gene could assemble onto the outer surface of liposomes and sculpt the membrane into tubular structures. We finally discuss the remaining challenges for building up a self reproducing minimal cell, in particular the coupling of the division machinery with volume expansion and genome replication. PMID- 25136388 TI - Prevalence of group a Beta-hemolytic streptococcus oropharyngeal colonization in children and therapeutic regimen based on antistreptolysin levels: data from a city from southern Brazil. AB - The aim of this study is to determinate the prevalence of oropharyngeal colonization by group A beta-hemolytic Streptococcus (GABHS) in pediatric population of Ponta Grossa, a midsize city of southern Brazil; estimate the effectiveness of antistreptolysin-O (ASO), compared to culture, in presence of infection; and design an unpublished investigative algorithm of rheumatic fever's suspicion, based on needs identified in worldwide consensus. It is an epidemiologic, observational and transversal study, involving 180 children younger than 12 years. Secretion of posterior oropharynx was collected for culture; and peripheral blood for determination of ASO. Student-t and chi-square tests, with Yates correction, were performed for statistical analysis. The ASO cutoff was determined by Receiver Operating Characteristic (ROC) curve. The prevalence encountered was 3.9%, and 25.5% of the children showed reagent ASO. This serological test demonstrated quantitatively and qualitatively significant associations to the GABHS presence (p=0.0001 for both associations) throughout the ROC curve, 200 U Todd was the value that resulted in the best accuracy, demonstrating 100% of sensibility and 80% of specificity in the GAS infection documentation. Also, it was found that the value of 1.200 U represents a specificity of 100%. The results emphasize the need for similar studies in other populations, to provide better targeting of the diagnosis and treatment of oropharyngitis by GABHS, which in turn can prevent up to 80% the cases of rheumatic fever, and consequently, the chronic rheumatic heart disease. PMID- 25136390 TI - The PFNA(r) Augmented in Revision Surgery of Proximal Femur Fractures. AB - OBJECTIVES: Modern implants for proximal femur fracture treatment have clearly improved clinical results. However, complications, including cut-out and loss of reduction, requiring revision surgery still occur. A major challenge in these cases is a loss of bone stock due to the existing implant, which is usually exacerbated by osteoporosis. A potential solution is the augmentation of implants, for example, of the femoral neck blade using bone cement. MATERIALS AND METHODS: Ten patients (five loosening of femoral neck implant, two pseudarthrosis, two implant failures and one acute fracture) were included. The initial hardware was removed and a PFNA augmented was implanted. The perforated femoral neck blade was augmented using polymethyl methacrylate cement. Clinical and radiological follow-up was performed at a mean of 5.4 months (SD +/-4.34). The main outcome parameters were fracture healing and implant-related complications. RESULTS: Technical handling was uneventful in all cases. No cement leakage into the joint occurred in any of the cases. The mean amount of cement injected was 5.3 ml. The fracture healed during follow-up in all cases except two patients who died from causes unrelated to the procedure and prior to complete consolidation. Problem-free elective hardware removal of the PFNA augmented was performed in two cases. DISCUSSION: The PFNA augmented is a potential implant for joint-preserving revision surgery in proximal femur fractures. The augmentation improves implant anchorage in the impaired bone stock. In this preliminary series, no negative biological side effects of the cement (i.e. osteonecrosis) were observed. PMID- 25136389 TI - Treatment of femoral neck fracture with a minimal invasive surgical approach for hemiarthroplasty - clinical and radiological results in 180 geriatric patients. AB - PURPOSE: The Direct Anterior Approach (DAA) is well established as a minimal access approach in elective orthopaedic hip surgery. For the growing number of elderly patients with femoral neck fractures treated with Bipolar Hip Hemiarthroplasty (BHH), only a few results do exist. The study shows the clinical and radiological outcome for 180 patients treated by a modified DAA with BHH. MATERIALS AND METHODS: The data of 180 geriatric patients with medial femoral neck fractures were evaluated retrospectively. The general and surgical complications, mobilisation using the Timed Up and Go test (TUG), the social environment pre- and postoperative and the radiological results have been compared with established approaches for geriatric hip surgery. RESULTS: After joint replacement, 18 (10%) patients were developed pneumonia, of which 3 (1.7%) died during hospitalisation. In 7 cases (4%), surgical revision had to be carried out: three times (1.7%) because of a seroma, three times (1.7%) because of subcutaneous infection, and one time (0.6%) because the BHH was removed, owing to deep wound infection. One dislocation (0.6%) occurred, as well as one femoral nerve lesion (0.6%) occured. 88.3% of patients were mobilised on walkers or crutches; the Timed Up and Go Test showed a significant improvement during inpatient rehabilitation. 83% were discharged to their usual social environment, 10% were transferred to a short-term care facility and 7% were relocated permanently to a nursing home. 3/4 of patients had a cemented stem alignment in the range between -5 degrees and 5 degrees , while 2/3 of patients had a maximum difference of 1 cm in leg length. CONCLUSION: Using the modified DAA, a high patient satisfaction is achieved after implantation of a BHH. The rate of major complications is just as low as in conventional approaches, and rapid mobilisation is possible. PMID- 25136387 TI - Divided we stand: splitting synthetic cells for their proliferation. AB - With the recent dawn of synthetic biology, the old idea of man-made artificial life has gained renewed interest. In the context of a bottom-up approach, this entails the de novo construction of synthetic cells that can autonomously sustain themselves and proliferate. Reproduction of a synthetic cell involves the synthesis of its inner content, replication of its information module, and growth and division of its shell. Theoretical and experimental analysis of natural cells shows that, whereas the core synthesis machinery of the information module is highly conserved, a wide range of solutions have been realized in order to accomplish division. It is therefore to be expected that there are multiple ways to engineer division of synthetic cells. Here we survey the field and review potential routes that can be explored to accomplish the division of bottom-up designed synthetic cells. We cover a range of complexities from simple abiotic mechanisms involving splitting of lipid-membrane-encapsulated vesicles due to physical or chemical principles, to potential division mechanisms of synthetic cells that are based on prokaryotic division machineries. PMID- 25136391 TI - Private and Non-Private Disc Herniation Patients: Do they Differ? AB - OBJECTIVES: In the 2006 yearly report from the Swedish National Register for Lumbar Spine Surgery it was claimed that international studies show obvious differences between private and non-private patients with regard to results from back surgery. Therefore our aim was to reveal such possible differences by comparing the two categories of patients at a private clinic. MATERIAL AND METHODS: The material comprises 1184 patients operated on for lumbar disc herniation during the period of 1987 to 2007. Basic pre-operative data were obtained from the medical records and follow-up was performed by a questionnaire around 5 years post-operatively. RESULTS: Small but statistically significant differences between private and non-private patients were seen pre-operatively regarding the proportions of a/ men and women in the samples, b/ those with physically demanding jobs, c/ those on sick leave and d/ those with lumbar pain. Over the years the admitted private patients had a decreasing mean duration of symptoms which was not seen in the non-private patients. No apparent differences (n.s.) were seen between the two categories of patients pre-operatively regarding age, presence and level of leg pain or the proportion who smoked. Post-operative improvement in leg and lumbar pain was very similar in private and non-private patients as was satisfaction with the results and the proportion of patients returning to work. CONCLUSION: Despite small pre-operative differences concerning some variables and a significant difference in symptom duration between private and non-private disc herniation patients, the final clinical results were very similar. PMID- 25136392 TI - Lack of relationship between occupational workload and microscopic alterations in lumbar intervertebral disc disease. AB - OBJECTIVES: The study investigated the impact of occupational workloads on disc surgery specimens. We report the relationship between workload and histological features. METHODS: Specimens were collected prospectively from patients suffering from lumbar disc prolapse (n=90) or spinal osteochondrosis (n=19). Histomorphology and occupational workload data and histomorphological features were evaluated. Occupational data were collected in a structured, standardized patient interview assessing lifting and carrying loads. In this way the exposure was assessed for each test subject's entire working life up to surgery. RESULTS: There was no association between cumulative workload and histological patterns. In a subgroup of patients with a workload period of 12 months prior to surgery a relevant formation of chondrocyte clusters (p=0.055) was apparent. Chondrocyte cluster formation was found in 83% (n=74) of the prolapse patients and in 58% (n=11) of the osteochondrosis patients (p=0.02). Fibrocyte mediated scar formation was found in 55% of the prolapse patients and in 45% of the spinal stenosis patients. Chondrocyte clusters and their de novo collagen matrix did not integrate biomechanically sufficient with collagen fibers of the disc. Disintegration of clusters from disc matrix and formation of intra-discal sequesters were observed. CONCLUSION: Matrix degeneration was common but displayed no relationship to occupational workload or other histological features. Scar formation was observed in every second specimen. Regenerative chondrocyte cluster proliferation was a common feature in disc specimens and tended to be associated in patients with a workload one year before surgery. PMID- 25136393 TI - Adherence to treatment: practice, education and research in Danish community pharmacy. AB - OBJECTIVE: To describe the practice, education and research concerning medication adherence in Danish community pharmacy. METHODS: The authors supplemented their expertise in the area of medication adherence through their contacts with other educators and researchers as well as by conducting searches in the Danish Pharmacy Practice Evidence Database, which provides annually updated literature reviews on intervention research in Danish pharmacy practice. RESULTS: PRACTICE: Medication adherence is the focus of and/or is supported by a large number of services and initiatives used in pharmacy practice such as governmental funding, IT-supported medicine administration systems, dose-dispensing systems, theme years in pharmacies on adherence and concordance, standards for counselling at the counter, pharmacist counselling, medication reviews and inhaler technique assessment. Education: In Denmark, pharmacy and pharmaconomist students are extensively trained in the theory and practice of adherence to therapy. Pharmacy staff can choose from a variety of continuing education and post-graduate programmes which address patient adherence. RESEARCH: Nine ongoing and recently completed studies are described. Early research in Denmark comprised primarily smaller, qualitative studies centred on user perspectives, whereas later research has shifted the focus towards larger, quantitative, controlled studies and action oriented studies focusing on patient groups with chronic diseases (such as diabetes, asthma, coronary vascular diseases). CONCLUSIONS: Our analysis has documented that Danish pharmaceutical education and research has focused strongly on adherence to treatment for more than three decades. Adherence initiatives in Danish community pharmacies have developed substantially in the past 5-10 years, and, as pharmacies have prioritised their role in health care and patient safety, this development can be expected to continue in future years. PMID- 25136394 TI - Measuring consumer preference for models of diabetes care delivered by pharmacists. AB - Evaluation of a community pharmacy disease management program for type 2 diabetes, 'SugarCare', was conducted. Compared with the standard care offered by pharmacists, this enhanced program offered patients closer monitoring of blood glucose levels, counselling about lifestyle, etc. The SugarCare study was funded by a grant but if the care is to continue some other method of financing must be found. OBJECTIVES: This study aimed to measure consumer preference for one of the two types of care offered in the SugarCare study, the control/standard and the intervention/enhanced service; the strength of that preference; and participants' willingness to pay (WTP) for their preferred care. METHODS: SugarCare was a parallel groups, control versus intervention, repeated measures design conducted in three areas of NSW, Australia. Patients in the Intervention group (enhanced care) had one initial visit to the pharmacy with six follow up visits over approximately 9 months. At these visits blood glucose was downloaded and patient care issues addressed. At the end of the service, a survey instrument was mailed to the intervention and control participants who were asked to read it and then expect a telephone call within 2 weeks of receipt. Responses were requested over the phone and the survey instrument completed by the researcher. WTP data were collected using a modified payment card method. RESULTS: Overall, 44/75 (59%; 47% 70% 95%CI) respondents expressed a preference for Scenario B (the enhanced care) while 31/75 (41%; 31%-52% 95%CI) preferred Scenario A (standard care) however, the difference was not statistically significant. The median maximum WTP was AUD10 for the enhanced care and AUD3.50 for the standard care (p<0.03). CONCLUSIONS: While the WTP values expressed were significantly higher for the enhanced care they did not match with the cost providing that diabetes care. Discrete choice analysis has the potential to overcome some of the difficulties encountered with the contingent valuation technique used here. Further research is required before WTP values such as these could be used with confidence to determine funding policy. PMID- 25136395 TI - Beta-blocker therapy in patients with left ventricular systolic dysfunction and chronic obstructive lung disease in an ambulatory care setting. AB - OBJECTIVE: To evaluate beta blocker persistence six months after beta-blocker initiation or dose titration in heart failure (HF) patients with COPD compared to those without COPD. Secondary objectives included comparison of beta-blocker dose achieved, changes in left ventricular ejection fraction (LVEF) and incidence of hospitalizations or emergency department (ED) visits during follow-up. METHODS: We conducted a matched, retrospective, cohort study including 86 patients with COPD plus concomitant HF (LVEF <=40%) and 137 patients with HF alone. All patients were followed in an outpatient HF clinic. Eligible patients had a documented LVEF <=40% and were initiated or titrated on a beta-blocker in the HF clinic. Patients were matched based on LVEF (categorized as <= 20% or 21-40%), gender, and age (> or <=70 years). The primary outcome was beta blocker persistence at 6 months. Secondary outcomes were dose achieved, LVEF, and incidence of hospitalizations or ED visits. RESULTS: There were no differences between the COPD and non-COPD groups in beta-blocker persistence at six-month follow-up (94.2% vs. 93.4% respectively, adjusted p=0.842). The proportion of patients who achieved a daily metoprolol dose equivalent of at least 100 mg was similar between the groups (adjusted p=0.188). The percent of patients with at least one ED visit or hospitalization in the six-month post-titration period was substantial but similar between the groups (53.5% and 48.2% for COPD and non-COPD patients, respectively, adjusted p=0.169). CONCLUSION: Our results support the use of beta-blockers in the population of heart failure patients with COPD and without reactive airway disease. PMID- 25136396 TI - Evaluation of patient perceptions and outcomes related to anticoagulation point of-care testing in ambulatory care clinics. AB - Until recently, Prothrombin Time/International Normalized Ratio (PT/INR) measurements have typically been used to monitor patients on warfarin through institutional laboratories via venous puncture. The Point-of-Care Testing (POCT) device has revolutionized the patient care process by allowing for laboratory testing outside of the central laboratory. OBJECTIVE: To analyze humanistic and clinical outcomes in patients currently treated with warfarin and monitored through a pharmacist-managed anticoagulation clinic using point-of-care testing (POCT) device versus venipuncture within ambulatory care clinics at our institution. METHODS: All patients currently treated with warfarin therapy who were managed by clinical pharmacists for anticoagulation monitoring at the Medical University of South Carolina (MUSC) Family Medicine Center and University Diagnostic Center, were enrolled. Patients were asked to complete a satisfaction survey regarding their anticoagulation monitoring. In addition, data related to emergency department (ED) visits, hospitalizations and percent of time in the INR therapeutic range for 6 months pre- and post-implementation of POCT device was collected. This information was obtained through an electronic patient information database, Oacis. RESULTS: A total of 145 patients were included in the data collection from the two clinics. The majority (41%) of these patients were taking warfarin for atrial fibrillation. Satisfaction surveys were completed by 86 (59 %) of patients. The surveys revealed that POCT device was preferred over venipuncture in 95% of patients. Reasons for the preference included more face-to-face interaction, less wait time, less pain, less blood needed, and quicker results. Of the 145 patients who were included in the objective data analysis, no significant differences were found in the number of hospitalizations, ED visits, or percent of time in the INR therapeutic range pre- and post-implementation of POCT device. CONCLUSION: The results of this study demonstrate improvement in patient satisfaction with POCT compared to venipuncture, with limited value in clinical outcomes. PMID- 25136397 TI - Risk factors of self-reported adverse drug events among Medicare enrollees before and after Medicare Part D. AB - OBJECTIVES: Quantify risk factors for self-reported adverse drug events (ADEs) after the implementation of Medicare Part D, quantify self-reported ADEs before and after Medicare Part D and quantify the association between self-reported ADEs and increased use of prescription medication. METHODS: The design was a longitudinal study including an internet survey before Medicare Part D in 2005 (n=1220) and a follow-up survey in 2007 (n=1024), with n=436 responding to both surveys. Harris Interactive(r) invited individuals in their online panel to participate in this study. Individuals who were 65 or older, English speakers, US residents and enrolled in Medicare were included. Data collected and used in analysis included self-reported ADE, socio-demographics, self-rated health, number of medications, symptoms experienced, concern and necessity beliefs about medicines, number of pharmacies, and whether doses were skipped or stopped to save money. RESULTS: In 2007, reporting an ADE was related to concern beliefs, symptoms experienced and age. ADEs were experienced by 18% of respondents in 2005 and 20.4% in 2007. The average number of medications increased from 3.82 (SD=2.82) in 2005 to 4.32 (SD=3.20) in 2007 (t= -5.77, p<0.001). Among respondents who answered both surveys (n=436), 18.4% reported an ADE in 2005 while 24.3% reported an ADE in 2007. The increase in self-reported ADE was related to concern beliefs (OR=1.12, 95%CI=1.05, 1.19) and symptoms experienced (OR= 3.27, 95%CI=1.60, 6.69), not number of medications (OR=1.04, 95%CI=0.77, 1.41). CONCLUSION: Discussing elderly patients' beliefs about their medicines may affect their medication expectations, symptom interpretation and attributions and future medication attributions. PMID- 25136398 TI - Corporate social responsibility in countries with mature and emerging pharmaceutical sectors. AB - In recent decades the concept of Corporate Social Responsibility (CSR) has been adopted by many business sectors, including the pharmaceutical industry. However, in this and other sectors its application remains variable, particularly between mature and developing economies. Its stakeholders include pharmacy and medical students, their attitude to the involvement of companies in socially responsible activities will be important determinants of public response to the industry. OBJECTIVE: To investigate the knowledge, attitudes and practices of senior medical and pharmacy students towards the CSR concept in the pharmaceutical sector in mature (Germany) and developing (Russia) markets. METHODS: A questionnaire survey was carried out among senior pharmacy and medical students during the summer semester 2008 in two Russian and one German university. In each country 120 questionnaires were distributed. The response rate was 95% in Russia and 93% in Germany. RESULTS: Although the relevance of CSR was widely acknowledged by the students, very few were aware of CSR practices currently performed by companies. THE REPUTATION OF THE PHARMACEUTICAL INDUSTRY WAS GENERALLY POOR: less than 15% of respondents gave credence to the information provided in advertisements and fully supported pricing strategies as well as policies towards the developing countries. When choosing an employer more than 90% of respondents consider the policies affecting an employee directly as pivotal. However, for a high proportion of students (59% in Russia and 64% in Germany) socially irresponsible behavior by companies has a significant negative impact. CONCLUSIONS: This paper identifies practices which students believe should be a part of the CSR programmes for the pharmaceutical industry, and also some that should be abandoned. It recommends that corporate communication on CSR should be expanded. Key differences are seen in perceptions of students in Germany and Russia towards the extent of irresponsible actions and the variation between them. PMID- 25136399 TI - Knowledge and reported use of antibiotics amongst school-teachers in New Zealand. AB - Gaps in public knowledge about antibiotics have led to calls for public education campaigns about antibiotics, including education of school children. OBJECTIVE: This study investigates New Zealand primary school teachers' current level of knowledge about antibiotics, to assess whether this is adequate for providing accurate education for children. METHODS: Two hundred and sixty-six primary school teachers from 39 schools in four cities were interviewed about their knowledge and understandings of antibiotics, using a questionnaire. RESULTS: Teachers reported having little current involvement with antibiotics. There were gaps in the understanding of antibiotics amongst many of the teachers. Only about 60% knew that antibiotics were useful only in bacterial infections, many believed antibiotics were useful for colds and flu, and many did not know about antibiotic resistance. On the other hand, teachers largely reported appropriate patterns of antibiotic use. CONCLUSION: If teachers are to educate children about antibiotics, basic education about antibiotics and resistance will be required for school teachers. PMID- 25136400 TI - Impact of educational intervention on the pattern and incidence of potential drug drug interactions in Nepal. AB - OBJECTIVE: To study the impact of educational intervention on the pattern and incidence of potential drug-drug interactions (DDIs). METHOD: All patients admitted to Internal Medicine wards of Manipal Teaching Hospital during the study period were included. Patient details were collected using a patient profile form and the datum from the filled forms was analyzed using Micromedex electronic database. An intervention was carried out through a presentation during clinical meeting and personal discussion. The target groups for the intervention included doctors and the nurses. RESULTS: Altogether 435 patients during preintervention and 445 during postintervention were studied. The incidence of potential DDIs was 53% (preintervention) and 41% (postintervention) [chi-square =11.27, p=0.001]. The average number of drugs per patient was 8.53 (pre-intervention) and 7.32 (post-intervention) [t=3.493, p=0.001]. Sixty-four percent of the potential DDIs were of 'Moderate' type and 58% had a 'Delayed' onset in both the phases. Seventy percent of the potential DDIs during the pre-intervention phase and 61% during post-intervention phase had a 'Good' documentation status. Pharmacokinetic mechanism accounted for 45% of the potential DDIs during preintervention and 36% in the post-intervention phase. Cardiovascular drugs accounted for 36% of the potential DDIs during pre-intervention and 33.2% during post-intervention phase. Furosemide was the high risk drug responsible for DDIs in both phases. The most common potential DDIs observed were between amlodipine and atenolol (4.82%) (preintervention) and frusemide and aspirin (5.20%) (postintervention). CONCLUSION: There was an association between potential DDIs and age, sex, and polypharmacy. PMID- 25136401 TI - Collaboration with pharmacy services in a family practice for the medically underserved. AB - OBJECTIVES: Pharmacist-managed collaborative services in a family practice setting are described, and diabetes and hypertension outcomes are assessed. METHODS: Pharmacist-managed clinics, pharmacotherapy consultations, and drug information services are provided for a medically underserved, predominantly African American population. A pharmacy residency director, an ambulatory care pharmacy resident and three PharmD candidate student pharmacists work directly with physicians, nurse practitioners, nurses, and social workers to form an interdisciplinary health care team. Providers utilize pharmacy services through consultations and referrals. Collaboration outcomes were evaluated in twenty-two patients with diabetes and thirty hypertensive patients. Patients were retrospectively followed throughout their history with pharmacy service. Hemoglobin A1c (A1C) was tracked before referral to pharmacy services, 3 to 6 months after, and as the most current measure after at least 6 months. Blood pressure (BP) was observed before pharmacy involvement, 2 to 4 months later, and then currently for at least 4 months with the service. The mean of the most current markers was calculated, and the percent of patients at their goal marker was compared to national averages. RESULTS: Fifty percent of pharmacy service patients met the American Diabetes Association hemoglobin A1c goal of less than 7% in our evaluation compared to the national mean of 49.8% overall and 44% in African Americans. Thirty percent of patients were at their BP goal while 33.1% of patients without diabetes and 33.2% of patients with diabetes nationally are at goal. CONCLUSION: The medically underserved patients under the care of pharmacy services achieved a higher percentage at their A1C goal than the national mean. The percentage of patients who achieved their BP goals was comparable to the national average. Increasing utilization of pharmacy services in the family practice setting allows for pharmacists and providers to form a trusted relationship while providing enhanced care and potentially improved outcomes for patients. PMID- 25136402 TI - Lung cell-specific modulation of LPS-induced TLR4 receptor and adaptor localization. AB - Lung infection by Gram-negative bacteria is a major cause of morbidity and mortality in humans. Lipopolysaccharide (LPS), located in the outer membrane of the Gram-negative bacterial cell wall, is a highly potent stimulus of immune and structural cells via the TLR4/MD2 complex whose function is sequentially regulated by defined subsets of adaptor proteins. Regulatory mechanisms of lung specific defense pathways point at the crucial role of resident alveolar macrophages, alveolar epithelial cells, the TLR4 receptor pathway, and lung surfactant in shaping the innate immune response to Gram-negative bacteria and LPS. During the past decade intracellular spatiotemporal localization of TLR4 emerged as a key feature of TLR4 function. Here, we briefly review lung cell type and compartment-specific mechanisms of LPS-induced TLR4 regulation with a focus on primary resident hematopoietic and structural cells as well as modifying microenvironmental factors involved. PMID- 25136404 TI - Anandamide protects HT22 cells exposed to hydrogen peroxide by inhibiting CB1 receptor-mediated type 2 NADPH oxidase. AB - BACKGROUND: Endogenous cannabinoid anandamide (AEA) protects neurons from oxidative injury in rodent models; however the mechanism of AEA-induced neuroprotection remains to be determined. Activation of neuronal NADPH oxidase 2 (Nox2) contributes to oxidative damage of the brain, and inhibition of Nox2 can attenuate cerebral oxidative stress. We aimed to determine whether the neuronal Nox2 was involved in protection mediated by AEA. METHODS: The mouse hippocampal neuron cell line HT22 was exposed to hydrogen peroxide (H2O2) to mimic oxidative injury of neurons. The protective effect of AEA was assessed by measuring cell metabolic activity, apoptosis, lactate dehydrogenase (LDH) release, cellular morphology, intracellular reactive oxygen species (ROS), and antioxidant and oxidant levels and Nox2 expression. RESULTS: HT22 cells exposed to H2O2 demonstrated morphological changes, decreased LDH release, reduced metabolic activity, increased levels of intracellular ROS and oxidized glutathione (GSSG), reduced levels of superoxide dismutase (SOD), and reduced glutathione (GSH) and increased expression of Nox2. AEA prevented these effects, a property abolished by simultaneous administration of CB1 antagonist AM251 or CB1-siRNA. CONCLUSION: Nox2 inhibition is involved in AEA-induced cytoprotection against oxidative stress through CB1 activation in HT22 cells. PMID- 25136405 TI - Transconjunctival inferior orbitotomy: indications, surgical technique, and complications. AB - Surgical access to the inferior orbit can be accomplished through either a transcutaneous or transconjunctival incision. The preferred approach should provide adequate surgical exposure with the fewest adverse effects. The purpose of this article is to review the literature on the transconjunctival incision and to discuss the indications and complications of the approach. The authors also discuss their preferred technique and provide a step-by-step instruction. The transconjunctival approach provides good surgical access with a low incidence of complications and a better aesthetic outcome than transcutaneous approaches. PMID- 25136403 TI - A review on hemeoxygenase-2: focus on cellular protection and oxygen response. AB - Hemeoxygenase (HO) system is responsible for cellular heme degradation to biliverdin, iron, and carbon monoxide. Two isoforms have been reported to date. Homologous HO-1 and HO-2 are microsomal proteins with more than 45% residue identity, share a similar fold and catalyze the same reaction. However, important differences between isoforms also exist. HO-1 isoform has been extensively studied mainly by its ability to respond to cellular stresses such as hemin, nitric oxide donors, oxidative damage, hypoxia, hyperthermia, and heavy metals, between others. On the contrary, due to its apparently constitutive nature, HO-2 has been less studied. Nevertheless, its abundance in tissues such as testis, endothelial cells, and particularly in brain, has pointed the relevance of HO-2 function. HO-2 presents particular characteristics that made it a unique protein in the HO system. Since attractive results on HO-2 have been arisen in later years, we focused this review in the second isoform. We summarize information on gene description, protein structure, and catalytic activity of HO-2 and particular facts such as its cellular impact and activity regulation. Finally, we call attention on the role of HO-2 in oxygen sensing, discussing proposed hypothesis on heme binding motifs and redox/thiol switches that participate in oxygen sensing as well as evidences of HO-2 response to hypoxia. PMID- 25136407 TI - Reconstruction of irradiated mandible after segmental resection of osteoradionecrosis-a technique employing a microvascular latissimus dorsi flap and subsequent particulate iliac bone grafting. AB - The fibula osteocutaneous flap has revolutionized the options of mandibular segmental defect bridging in osteoradionecrosis (ORN). In selected cases, however, the fibula flap is not an option because of atherosclerosis or other features that compromise the vascularity of the lower leg and foot. The aim of this study is to present an alternative method of mandibular segmental reconstruction employing a latissimus dorsi (LD) flap and subsequent particulate iliac free bone graft reconstruction. In 15 patients with ORN, a mandibular segmental defect was bridged with a reconstruction plate, and the defect site was primed with a LD musculocutaneous flap wrapped around the reconstruction plate to bring in vascularized tissue and optimize healing conditions for a subsequent particulate iliac free bone graft reconstruction. The management of defect closure was successful in all 15 patients. Twelve patients had a subsequent bone grafting from the posterior ileum for repair of defects up to 14 cm length. Three patients had no bone graft for various reasons. In three patients dental rehabilitation was achieved with implant supported prosthodontic appliances. Ten patients met the success criteria of uneventful graft healing with restitution of osseous continuity, mandibular height, symmetry and function, and avoidance of reconstruction plate fracture. PMID- 25136408 TI - Survey of Common Practices among Oculofacial Surgeons in the Asia-Pacific Region: Management of Orbital Floor Blowout Fractures. AB - A web-based anonymous survey was performed to assess common practices of oculofacial surgeons in the management of traumatic orbital floor blowout fractures. A questionnaire which contained questions on several controversial topics in the management of orbital floor fractures was sent out via e-mail to 131 oculofacial surgeons in 14 countries in the Asia-Pacific region. A total response rate of 58.3% was achieved from May to December 2012. The preferred time for surgical intervention was within 2 weeks for adult patients, porous polyethylene implant was the most popular choice, and most surgeons preferred the transconjunctival approach. Postoperatively, diplopia was the most commonly encountered complication and most oculofacial surgeons reviewed their patients regularly for up to 12 months. We report the results of the first survey of oculofacial surgeons within the Asia-Pacific region on the management of orbital floor blowout fractures. Compared with previous surveys (from year 2000 to 2004), the duration to surgical intervention was comparable but there was a contrasting change in preferred surgical approach and choice of orbital implant. PMID- 25136406 TI - Management of carotid artery trauma. AB - With increased awareness and liberal screening of trauma patients with identified risk factors, recent case series demonstrate improved early diagnosis of carotid artery trauma before they become problematio. There remains a need for unified screening criteria for both intracranial and extracranial carotid trauma. In the absence of contraindications, antithrombotic agents should be considered in blunt carotid artery injuries, as there is a significant risk of progression of vessel injury with observation alone. Despite CTA being used as a common screening modality, it appears to lack sufficient sensitivity. DSA remains to be the gold standard in screening. Endovascular techniques are becoming more widely accepted as the primary surgical modality in the treatment of blunt extracranial carotid injuries and penetrating/blunt intracranial carotid lessions. Nonetheless, open surgical approaches are still needed for the treatment of penetrating extracranial carotid injuries and in patients with unfavorable lesions for endovascular intervention. PMID- 25136409 TI - Managing the frontal sinus in the endoscopic age: has the endoscope changed the algorithm? AB - Management of fractures involving the frontal sinus seems to be more complex than merely obtaining an ideal reduction of the bony injuries. Multiple articles on the management of these fractures suggest that a great deal of controversy persists despite many years of surgical experience. The question posed in this article is whether or not the advent of endoscopic approaches has changed or should change the approaches/algorithms used in the management of these challenging fractures. It is the conclusion of these authors that endoscopic techniques can indeed allow us to change the algorithm for management of frontal sinus trauma. New algorithms are proposed that should provide guidance to craniomaxillofacial surgeons treating these injuries in the endoscopic age. PMID- 25136410 TI - Versatility of adipofascial anterolateral thigh flap for reconstruction of maxillary defects with infratemporal fossa extension. AB - Tumors arising from the posterior hard palate or posterolateral maxilla may extend to involve the infratemporal fossa (ITF). Resection of these tumors results in infrastructural maxillectomy with ITF defects. In this study, we describe the use of an adipofascial anterolateral thigh flap (ALT) specifically for such defects. This case series includes four patients who underwent an infrastructure maxillectomy with ITF clearance and the resultant defects were reconstructed using adipofascial anterolateral thigh flaps. The complications as well as the functional outcomes were assessed. This study included patients with lesions involving the hard palate, posterolateral part of maxilla with extension into the ITF. The mean flap dimension was 150 cm(2) (range, 120-180 cm(2)). All flaps were harvested based on a single perforator. The flap was used to obliterate the ITF defect and also to achieve oroantral separation. All flaps mucosalized well within 6 weeks. All patients were on oral diet and had adequate mouth opening. There were no donor-site complications. Adipofascial ALT is an excellent choice for infrastructural maxillectomy defects with ITF extension. The intraoral part got mucosalized well and provided a smooth and taut surface. A large adipofascial tissue flap helps obliterate the ITF, thus minimizing complications. PMID- 25136411 TI - A Biomechanical Comparison of Three 1.5-mm Plate and Screw Configurations and a Single 2.0-mm Plate for Internal Fixation of a Mandibular Condylar Fracture. AB - The most stable pattern of internal fixation for mandibular condyle fractures is an area of ongoing discussion. This study investigates the stability of three patterns of plate fixation using readily available, commercially pure titanium implants. Finite element models of a simulated mandibular condyle fracture were constructed. The completed models were heterogeneous in bone material properties, contained approximately 1.2 million elements and incorporated simulated jaw adducting musculature. Models were run assuming linear elasticity and isotropic material properties for bone. No human subjects were involved in this investigation. The stability of the simulated condylar fracture reduced with the different implant configurations, and the von Mises stresses of a 1.5-mm X-shaped plate, a 1.5-mm rectangular plate, and a 1.5-mm square plate (all Synthes (Synthes GmbH, Zuchwil, Switzerland) were compared. The 1.5-mm X plate was the most stable of the three 1.5-mm profile plate configurations examined and had comparable mechanical performance to a single 2.0-mm straight four-hole plate. This study does not support the use of rectangular or square plate patterns in the open reduction and internal fixation of mandibular condyle fractures. It does provide some support for the use of a 1.5-mm X plate to reduce condylar fractures in selected clinical cases. PMID- 25136412 TI - Incidence, etiology, and patterns of maxillofacial fractures in ain-shams university, cairo, egypt: a 4-year retrospective study. AB - Although there is a worldwide increase in maxillofacial trauma incidence; the pattern and etiology of these injuries varies from one country to another depending on socioeconomic, cultural, and environmental factors. This study aims to realize the epidemiological characteristics of maxillofacial fractures in our department. A retrospective cross-sectional study of all facial trauma patients admitted to our department during 2009 to 2012. Patients' data including gender, age, etiology of trauma, the pattern and demographic distribution of fractures of maxillofacial skeleton, and associated injuries were analyzed and compared with previously published data. The chi-square test was used with a p value of less than 0.05, which was considered statistically significant. There is a significant increase in maxillofacial fractures incidence in the past 2 years than former ones. There is a male predominance with highest incidence in the age group of 20 to 40 years. Road traffic accident is the most common etiological factor followed by violence. There is increase in mandibular fracture incidence compared with midface. The significant increased incidence of maxillofacial fracture due to motor car accidents and assaults in the past 2 years reflects a behavioral change within the community. PMID- 25136413 TI - Variations in emergence and course of the inferior palpebral nerve. AB - Comprehensive understanding of the anatomy of the inferior palpebral (IP) nerve is crucial to preservation of sensation in the inferior eyelid and conjunctiva. Iatrogenic injuries may occur during blepharoplasty, repair of orbitozygomatic fracture and other maxillofacial surgeries involving this region. Although several studies depict the anatomical variations of the main infraorbital nerve (ION), little information exclusive to the IP nerve exists. This study provides information on the additional variations of the ION with reference to the IP nerve. The study was performed on 84 IP nerves by dissection of 42 formalin-fixed cadavers from the laboratory of topographic anatomy, Department of Human Anatomy, University of Nairobi, Kenya. Each of the nerves were exposed at the emergence and followed to their termination. Variations encountered involved emergence, course, and even absence. Variant emergence was through an accessory infraorbital foramen, an infraorbital notch, and as a common trunk with the external nasal nerve. This nerve shows high anatomical variability that may account for the difficulties and complications encountered in clinical interventions. It is believed that this information will improve clinical management of conditions affecting the region of distribution of the IP nerve. PMID- 25136414 TI - Orbital fracture leading to severe multifascial space infection including the parapharyngeal space: a report of a case and review of the literature. AB - Orbital trauma can result in periorbital and orbital infections. Orbital infections have been classified by Chandler et al in 1970 to their anatomic location and boundaries. This case report describes a patient who developed a severe orbital infection following orbital fractures. The infection progressed to the parapharyngeal space. The patient required multiple incision and drainage surgeries and tissue debridements to have clinical resolution. To our knowledge, there has not been a case described in the literature of an orbital infection progressing to the parapharyngeal space. A literature review of orbital trauma leading to infection discusses the pathogenesis of the infections. This case demonstrates that close clinical follow-up and appropriate medical management of comorbidities that put a patient at higher risk of developing an infection is of the utmost importance in the treatment of maxillofacial trauma patients. PMID- 25136415 TI - Subclavicular pectoralis major myocutaneous flap for optimal reconstruction of large orbitozygomatic defects: a case report. AB - Since the introduction of microvascular free flaps, the pectoralis major myocutaneous flap (PMMF) has been relegated to background for most reconstructive surgeons. The objective of this article is to show the advantages of cervicofacial defects reconstruction with PMMF using the subclavicular plane route in a challenging clinical case. An 83-year-old man presented with cutaneous temporomalar lesion with orbital spread. Tumor resection was performed, including 12 * 11 cm skin and subcutaneous tissue, overlying zygomatic and malar bone, and orbital exenteration. Radical parotidectomy and functional neck dissection were performed. PMMF was chosen as reconstructive option routing the pedicle to the subclavicular plane. The length of the pedicle was 31 cm. The subclavicular route for PMMF increases the flap's length and arc of rotation compared with the conventional supraclavicular one. This procedure decreases the bulk of the PMMF pedicle which makes it functionally and cosmetically favorable. By using this modification, we may widen the "safe" reconstructive possibilities. PMID- 25136416 TI - Interesting case: displacement of fractured maxilla into pharyngeal space. AB - Atypical fracture patterns of the facial region have been reported infrequently. An unusual displacement of fractured posterior maxillary segment into the lateral pharyngeal space is described. PMID- 25136417 TI - Influence of adhesive systems on microtensile bond strength of resin-based endodontic sealers to the root dentin. AB - OBJECTIVE: The aim of this study was to determine the microtensile bond strength to root dentin of AH PlusTM and EndoREZ(r) with Clearfil Liner Bond 2V and Optibond SoloTM Plus adhesive systems. STUDY DESIGN: The coronal and middle thirds of six single rooted bovine teeth was split longitudinally in a mesio distal direction. The two halves were joined with AH Plus or EndoREZ, with and without the use of Clearfil Liner Bond 2V and Optibond SoloTM Plus adhesive systems. Build-ups were vertically sectioned into quadrangular (~1mmx1mm) compound bars and subjected to tensile tests at a constant crosshead speed (1 mm/min) until debonding. RESULTS: Optibond(r) Solo PlusTM in combination with AH PlusTM and EndoREZ(r) showed the highest mean microtensile bond strength values, in both coronal and middle thirds. The lowest results were seen in the groups where no dentine adhesive was applied, and in those where the self-etching adhesive Clearfil Liner Bond 2V was used. CONCLUSION: The microtensile bond strength to root dentin of AH PlusTM and EndoREZ may be increased with the use of a total-etch adhesive. Key words:Adhesive systems, AH Plus, EndoREZ, microtensile bond strength, root dentin. PMID- 25136418 TI - Occurrence of contralateral lymph neck node metastasis in patients with squamous cell carcinoma of the oral cavity. AB - INTRODUCTION: Squamous cell carcinoma represents about 90% of malignancies of the mouth and about 38% of the head and neck tumors. The behavior of the cancer is very aggressive, presenting early cervical metastasis and, often contralateral ranging from 0.9 to 36%. OBJECTIVES: This study aims to analyze clinical and pathological factors that may influence metastasis of squamous cell carcinoma in cervical lymph nodes and relate this occurrence in the contralateral primary tumor, with disease prognosis and the interference of this type of metastasis in the survival rate of patients with this pathology. Material and Metohds: It was conducted a retrospective study from medical records of patients with Squamous Cell Carcinomas with homolateral lymph node metastasis and contralateral attended at the clinic of Head and neck surgery of Hospital Sao Vicente de Paulo in Passo Fundo - RS - Brazil, from 2000 to 2008. RESULTS: Analyzing the charts of patients with metastatic and metastatic contralateral side it was observed that patients with initial stage presented a higher survival with statistical significance (p=0,035). CONCLUSIONS: The occurrence of metastases in lymph nodes of contralateral position to the primary lesion was not the main fator that influenced the survival of the group. Key words:Squamous cell carcinoma, oral cavity, contralateral, death rate, lymphatic metastasis, prognosis. PMID- 25136419 TI - Association of chronic periodontitis with white blood cell and platelet count - A Case Control Study. AB - OBJECTIVES: The objective of the study was to determine whether plasma levels of white blood corpuscles (WBCs) and platelets were altered in patients with chronic periodontitis compared to healthy controls. STUDY DESIGN: A total of 120 subjects, 60 with chronic periodontitis and 60 with healthy periodontium of age group 30-50 years were selected for the study. Oral hygiene status and pocket probing depth were measured. During clinical evaluation, venous blood samples were taken to analyze the WBC and platelet counts. Statistical analysis was utilized to compare differences across various groups. RESULTS: The WBC count was higher in patients with chronic periodontitis when compared with controls whereas the platelet count was lower in the case group. CONCLUSIONS: Elevated WBC count plays a key role in chronic periodontitis and in turn a risk factor for cardiovascular diseases. However, there is no significant role of platelets in periodontal infection even though it has a major role in atherogenesis. Key words:Periodontitis, white blood cells, platelets, cardiovascular diseases. PMID- 25136420 TI - Clinical evaluation of subepithelial connective tissue graft and guided tissue regeneration for treatment of Miller's class 1 gingival recession (comparative, split mouth, six months study). AB - OBJECTIVES: The present study aims to clinically compare and evaluate subepithelial connective tissue graft and the GTR based root coverage in treatment of Miller's Class I gingival recession. STUDY DESIGN: 30 patients with at least one pair of Miller's Class I gingival recession were treated either with Subepithelial connective tissue graft (Group A) or Guided tissue regeneration (Group B). Clinical parameters monitored included recession RD, width of keratinized gingiva (KG), probing depth (PD), clinical attachment level (CAL), attached gingiva (AG), residual probing depth (RPD) and % of Root coverage(%RC). Measurements were taken at baseline, three months and six months. A standard surgical procedure was used for both Group A and Group B. Data were recorded and statistical analysis was done for both intergroup and intragroup. RESULTS: At end of six months % RC obtained were 84.47% (Group A) and 81.67% (Group B). Both treatments resulted in statistically significant improvement in clinical parameters. When compared, no statistically significant difference was found between both groups except in RPD, where it was significantly greater in Group A. CONCLUSIONS: GTR technique has advantages over subepithelial connective tissue graft for shallow Miller's Class I defects and this procedure can be used to avoid patient discomfort and reduce treatment time. Key words:Collagen membrane, comparative split mouth study, gingival recession, subepithelial connective tissue graft, guided tissue regeneration (GTR). PMID- 25136421 TI - How much incisor decompensation is achieved prior to orthognathic surgery? AB - OBJECTIVES: To quantify incisor decompensation in preparation for orthognathic surgery. STUDY DESIGN: Pre-treatment and pre-surgery lateral cephalograms for 86 patients who had combined orthodontic and orthognathic treatment were digitised using OPAL 2.1 [http://www.opalimage.co.uk]. To assess intra-observer reproducibility, 25 images were re-digitised one month later. Random and systematic error were assessed using the Dahlberg formula and a two-sample t test, respectively. Differences in the proportions of cases where the maxillary (1100 +/- 60) or mandibular (900 +/- 60) incisors were fully decomensated were assessed using a Chi-square test (p<0.05). Mann-Whitney U tests were used to identify if there were any differences in the amount of net decompensation for maxillary and mandibular incisors between the Class II combined and Class III groups (p<0.05). RESULTS: Random and systematic error were less than 0.5 degrees and p<0.05, respectively. A greater proportion of cases had decompensated mandibular incisors (80%) than maxillary incisors (62%) and this difference was statistically significant (p=0.029). The amount of maxillary incisor decompensation in the Class II and Class III groups did not statistically differ (p=0.45) whereas the mandibular incisors in the Class III group underwent statistically significantly greater decompensation (p=0.02). CONCLUSIONS: Mandibular incisors were decompensated for a greater proportion of cases than maxillary incisors in preparation for orthognathic surgery. There was no difference in the amount of maxillary incisor decompensation between Class II and Class III cases. There was a greater net decompensation for mandibular incisors in Class III cases when compared to Class II cases. Key words:Decompensation, orthognathic, pre-surgical orthodontics, surgical-orthodontic. PMID- 25136423 TI - Estimation of serum lipids in patients with Oral Submucous Fibrosis in India. AB - OBJECTIVES: Oral submucous fibrosis (OSMF) is the most prevalent precancerous condition in India. Low levels of lipids serves as a marker and prognostic indicator in the early detection of oral precancerous and cancerous states. In spite of the high prevalence and its potential to undergo malignant transformation, this condition has not widely been investigated with respect to the serum lipid levels. In the present study, an attempt was made to analyze the complete serum lipid profile, total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and very low density lipoprotein (VLDL) cholesterol in OSMF and controls. MATERIAL AND METHODS: The study was conducted in 45 clinically and histopathologically diagnosed cases of OSMF and 45 age and sex matched controls. The complete lipid profile including TC, TG, HDL cholesterol, LDL cholesterol and VLDL cholesterol was analyzed. RESULTS: The serum lipid levels were significantly lower in the patients with OSMF than in the controls. When the values were compared between different disease stages, the maximum reduction of lipids was evident for stage 3 OSMF. From the present results, it is evident that the level of serum lipids decreases with progression of the disease. CONCLUSIONS: From these findings, it appears that the decrease in the lipid levels may be considered as a useful marker in the early diagnosis of oral premalignant condition like OSMF. Key words:Oral submucous fibrosis, lipids, premalignant condition. PMID- 25136422 TI - Clinical and radiographical evaluation of the healing of large periapical lesions using triple antibiotic paste, photo activated disinfection and calcium hydroxide when used as root canal disinfectant. AB - OBJECTIVES: To evaluate clinically and radio graphically, the healing following nonsurgical treatment of periapical lesions when Photo Activated Disinfection(PAD), triple antibiotic paste and calcium hydroxide was used as root canal disinfectant. MATERIAL AND METHODS: Sixty patients (20 for PAD, 20 for triple antibiotic paste, 20 for calcium hydroxide) with periapical lesions in the maxillary and mandibular anterior region were selected from the outpatient section of the Department of Conservative Dentistry & Endodontics, Govt. Dental College, Kozhikode to participate in this study. The patients were selected with a preoperative score of 4 or 5. There were no significant differences for the PAI Scores between the three groups at the start of the experiment .Intracanal disinfection was done in the three groups followed by obturation. The patients recalled at 3,6,12,18 months interval. RESULTS: At 18 months follow up 15 % of cases failed in calcium hydroxide group,5% in triple antibiotic paste and no failure cases were seen in PAD group. Success criteria were divided into strict and loose, while the former had statistically significant p value the latter did not. Kruskal-Wallis Test showed an increased mean value for PDT and a significant change in p value. Bonferroni post hoc test was done to compare if there is any significant change between groups. Only significant change was found between calcium hydroxide and photoactivated disinfection . CONCLUSION: PAD was more effective intracanal disinfectant at 6,12 and 18 months. Key words:Calcium, hydroxide, photo activated disinfection, triple antibiotic paste, root canal disinfection. PMID- 25136424 TI - Gingival recession: prevalence and risk indicators among young greek adults. AB - OBJECTIVES: The aim of the current research was to assess the prevalence of gingival recession and to investigate possible associations among this condition, periodontal and epidemiological variables in a sample of young Greek adults in a general dental practice. MATERIAL AND METHODS: A total of 1,430 young adults was examined clinically and interviewed regarding several periodontal and epidemiological variables. Collected data included demographic variables, oral hygiene habits and smoking status. Clinical examination included the recording of dental plaque, supragingival calculus presence, gingival status and buccal gingival recession. Multivariate logistic regression analysis model was performed to access the possible association between gingival recession and several periodontal and epidemiological variables as potential risk factors. RESULTS: The overall prevalence of gingival recession was 63.9%. The statistical analysis indicated that higher educational level [OR= 2.12, 95% CI= 0.53-8.51], cigarette smoking [OR= 1.97, 95% CI= 1.48-7.91], frequent tooth brushing [OR= 0.98, 95% CI= 0.56-1.96], presence of oral piercing [OR= 0.92, 95% CI= 0.38-1.58], presence of gingival inflammation [OR= 4.54, 95% CI= 1.68-7.16], presence of dental plaque [OR= 1.67, 95% CI= 0.68-2.83] and presence of supragingival calculus [OR=1.34, 95% CI= 0.59-1.88], were the most important associated factors of gingival recession. CONCLUSIONS: The observations of the current research supported the results from previous authors that several periodontal factors, educational level and smoking were significantly associated with the presence of gingival recession, while presence of oral piercing was a new factor that was found to be associated with gingival recession. Key words:Gingival recession, prevalence, risk factors, young adults. PMID- 25136425 TI - Correlation between mutans streptococci counts of parents and their children residing in Chandigarh, India. AB - OBJECTIVES: To determine the prevalence of Mutans Streptococci (MS) in children and to evaluate the relationship between the salivary levels of MS in children and their parents. MATERIAL AND METHODS: 100 children aged 3-6 years along with their parents (100 mothers and fathers each) were included in the study. The children were segregated depending upon their age and level of caries experience. The children were examined clinically on an ordinary chair in natural daylight using the Moller's index criteria. Assays for Mutans Streptococci (MS) were done for both the children and their parents using the Dentocult SM strip mutans test. Collected data was assessed using SPSS software. RESULTS: The overall prevalence of MS in the children was 83%. A statistically significant correlation (p<0.05) was observed between salivary MS counts of children and their mothers. No significant correlation was seen with the fathers. CONCLUSIONS: The findings conclude that if primary caregivers harbour high levels of MS in their saliva, it is likely that their children will have the same. Key words:Mutans streptococci, parents, children, dentocult SM kits. PMID- 25136426 TI - Proposed new grading of oral submucous fibrosis based on cheek flexibility. AB - OBJECTIVES: Oral submucous fibrosis (OSMF) is a potentially malignant disorder of oral cavity, pharynx and upper digestive tract, characterized by progressive inability to open the mouth. Based on clinical and/or histopathological features, various classifications and grading systems have been put forth till date. The aim of the present study was to study the variance in cheek flexibility in OSMF patients, the observance of which led to the introduction of a new grading for the condition. MATERIAL AND METHODS: The study included 412 patients with OSMF attending to the Department of Oral Medicine and Radiology during the period from December 2008 to June 2013. A detailed history and examination of the patients was performed with special emphasis on measuring cheek flexibility. Statistical analysis was done using Chi-square test and p<0.05 was considered to be statistically significant. RESULTS: The most common etiological factor was tobacco (73.3%). All the patients reported with burning sensation of the mouth and blanching of the mucosa. Malignancy was reported in only 4.6% patients. 60.4% patients showed cheek flexibility of 30mm and above, while 29.6% patients showed cheek flexibility between 20-30mm and 10% patients showed less than 30mm of cheek flexibility. CONCLUSION: The observations of the present study have led to the proposal of a new grading of OSMF based on cheek flexibility which could assist in the categorization of the condition by the clinicians. Key words:Cheek flexibility, oral submucous fibrosis, grading, areca nut. PMID- 25136428 TI - Comparative study of the efficacy of herbal antioxdants oxitard and aloe vera in the treatment of oral submucous fibrosis. AB - OBJECTIVES: Oral submucous fibrosis (OSMF) is a potentially malignant disorder predominantly seen in the Indian subcontinent due to areca nut, tobacco and their products. The aim of the present study was to compare the efficacy of oxitard and aloe vera in the management of OSMF. MATERIAL AND METHODS: 120 subjects with OSMF were included in the study. The patients were clinico-pathologically diagnosed and divided equally in 2 groups, Group A (oxitard group) and Group B (aloe vera group). Group A was administered 2 oxitard capsules twice daily and Group B was given 5 mg aloe vera gel to be applied topically thrice daily for 3 months. Different clinical parameters were evaluated at regular intervals. Data was analyzed using the Student's paired t test and Chi-square test. P-value <0.001 was considered to be statistically significant. RESULTS: Clinical improvements in mouth opening and tongue protrusion was significant in the oxitard group (p=0.0005). Subjective symptoms of pain associated with the lesion (p=0.0003), difficulty in swallowing (p=0.0000) and speech (p=0.0001) also significantly improved in the Group A. The improvement in burning sensation was not statistically significant between the 2 groups (p=0.002). There was a mild to moderate decrease in the size of the lesion. CONCLUSIONS: Though there is no definitive treatment for the condition however, overall assessment of symptoms like mouth opening, tongue protrusion, difficulty in swallowing and speech and pain associated with the lesion showed that oxitard capsules can bring about significant clinical improvements than aloe vera gel in the treatment of OSMF. Key words:Oral submucous fibrosis, oxitard capsules, aloe vera, burning sensation, mouth opening. PMID- 25136427 TI - Clinical, radiological and therapeutic features of keratocystic odontogenic tumours: a study over a decade. AB - Factors associated with the potential for recurrence of keratocystic odontogenic tumours (KCOT) still remain to be clearly determined and no consensus exists concerning the management of KCOT. The purpose of this study was to evaluate different clinical factors associated with KCOT and its treatment methods. A retrospective review was performed of 55 cases treated from 2001 to 2010. Of the 55 cases, 27% were associated with an impacted or semi-impacted tooth. The majority of the lesions (82%) were located in tooth-bearing areas, and the overall mandibular to maxilla ratio of tumour occurrence was 5:1. The treatment options included enucleation, marsupialisation, or peripheral ostectomy, with or without the use of Carnoy's solution. Recurrence was found in 14 cases (25%). No significant association was seen between recurrence and age, symptomatic cases, location of the lesion, or unilocular or multilocular appearance. The recurrence rate was higher in the group with tooth involvement, more marked in cases with third molar involvement. Statistical analysis showed a significant relation between recurrence and the type of treatment, with higher rates in cases treated with enucleation associated with tooth extraction. In our series, those cases with a closer relation with dental tissues showed a higher risk of recurrence, suggesting the need for a distinct classification for peripheral variants of KCOT. Key words:Keratocystic odontogenic tumour, Odontogenic keratocyst, Odontogenic cysts, Keratocyst, Carnoy's solution. PMID- 25136429 TI - Comparative study of mandibular linear measurements obtained by cone beam computed tomography and digital calipers. AB - OBJECTIVES: Cone beam computed tomography (CBCT) is an innovative dental of imaging system characterized by rapid volumetric imaging with patient exposure to a single dose of radiation. The present study was carried out to compare the linear measurements obtained with CBCT and digital caliper in 20 mandibles from human cadavers. STUDY DESIGN: A total of 4800 linear measurements were measured between different mandibular anatomical points with CBCT and digital caliper. The real measurements were defined as those obtained with the digital caliper. Posteriorly, the mandibles were scanned to obtain the CBCT images, with software based measurements of the distances. RESULTS: The measurements obtained with the digital caliper were greater. The CBCT technique underestimated distances greater than 100 mm. CONCLUSIONS: CBCT allows to obtain linear mandibular anatomical measurements equivalent to those obtained with digital caliper. The differences existing between both methods were clinically acceptable. Key words:Computed tomography, cone beam CT, accuracy, reliability, digital caliper. PMID- 25136430 TI - Hand skeletal maturity and its correlation with mandibular dental development. AB - OBJECTIVES: Assessment of pubertal status and pubertal growth spurt in orthodontic patients has a considerable impact on the diagnosis, treatment plan and the outcome of orthodontic treatments. Hand-wrist radiography is routinely used to evaluate skeletal development. Some studies have shown that there is an association between bone development and different stages of dental calcification; therefore, the stages of dental calcification can be used as the first tool for diagnosis, in case there is an association. This study was performed with the aim to evaluate the association between the phases of dental development and the stages of skeletal maturity. STUDY DESIGN: In this study, a total of 52 patients (26 males and 26 females), referring to Mashhad School of Dentistry for orthodontic treatment, were evaluated; the subjects were within the age range of 9-14 years. Hand-wrist radiographic evaluation of skeletal maturation was performed using Fishman method. Also, the Demirjian method was used to identify the stages of dental calcification by panoramic radiographs. Independent t-test and Spearman correlation coefficient were used for data analyses. RESULTS: The mean age of males and females was 11.05 +/- 1.05 and 10.62 +/- 1.12 years, respectively (p=0.156). The Spearman correlation coefficients between skeletal maturity indicators (SMIs) and developmental stages of mandibular left and right canines and second molars were significant in males only (p<0.05). Also, correlation coefficients were significant between adductor sesamoid ossification and mandibular right and left canines developmental stages in males (p<0.05). CONCLUSIONS: Findings of this study showed that the correlation between dental developmental stages and skeletal maturity only were significant in males; thus, different skeletal maturity patterns in males and females might be perceptible. Key words:Skeletal maturation, hand-wrist radiography, panoramic radiography. PMID- 25136431 TI - Conflict of interest reporting in dentistry meta-analyses: A systematic review. AB - OBJECTIVES: The issue of reporting conflicts of interest (COI) in medical research has come under scrutiny over the past decade. Absolute transparency is important when dealing with conflicts of interest to provide readers with all essential information required to make an informative decision of the results. The key objective of this study was to examine the prevalence of reporting conflicts of interest in therapeutic dental meta-analyses of Randomized Control Trials (RCTs), and to investigate possible associations with other categorical variables. STUDY DESIGN: We conducted an extensive literature search across multiple databases to search for relevant review articles for this study. We utilized pre-determined key words, and relied on three reviewers to test and review the use of a data extraction form that was used for the meta-analyses. Data regarding study characteristics, direction of results, and the significance of the results from each meta-analysis were extracted. RESULTS: There were 129 meta-analyses used in this review, and the reporting on conflict of interest was low with only 50 (38.8%) of the articles possessing a conflict of interest statement (either confirming of denying COI). Of these 50 articles, there were only 4 (8%) studies that reported an actual conflict of interest. A statement of conflicts of interest was found in 29 (35.3%) of the papers that reported significant findings, whereas 35% of the papers that reported positive results reported on conflict of interest. Prior to 2009, only 17 (25%) papers reported conflicts of interest, but since 2009, 54.1% of papers collected had a conflict of interest statement. CONCLUSIONS: Meta-analyses published in the field of dentistry do not routinely report author conflicts of interest. Although few conflicts appear to exist, the field of dentistry should continue to ensure that best evidence reports provide clear and transparent reporting of potential conflicts of interest in academic journals. Key words:Dentistry, dentition, meta analysis, quantitative review. PMID- 25136432 TI - The role of topical simvastatin on bone regeneration: A systematic review. AB - OBJECTIVES: The aim of this systematic review was to summarize the results concerning the use of simvastatin for promoting bone regeneration and to discuss the level of scientific evidence supporting such findings. MATERIAL AND METHODS: A Pubmed search using "Simvastatin"[Mesh] AND "Bone Regeneration"[Mesh] as Boolean operators was constrained to the last 10 years and only included papers written in English. RESULTS: Of the 41 relevant papers reviewed, most of them (76.2%) have been published in the last 5 years, and most of them address animal studies (66.6%) performed on rats or rabbits in extraoral regions. Only 4 randomized controlled trials (RCTs) assessed the role of topical simvastatin in periodontal patients. CONCLUSIONS: A large part of the evidence concerning the role of topical simvastatin on bone regeneration comes from animal studies (mainly rats) focusing on extraoral bone defects. Only the use of subgingival simvastatin after root scaling has been properly supported by RCT. Key words:Simvastatin, bone regeneration, topical administration, osteogenesis, osteoinduction. PMID- 25136434 TI - Sialolithiasis. Proposal for a new minimally invasive procedure: Piezoelectric surgery. AB - Sialolithiasis is the presence of stones in the ducts of the salivary glands. Most episodes are unique, and 60-80% are located exclusively in the main excretory duct. The main clinical manifestations are swelling and pain typically before, during or after meals that decreases if the obstruction is not complete. The highest prevalence of lithiasis is in the submandibular gland -87%-, whose secretion is more viscous, followed by the parotid gland -10%- and finally the sublingual gland -3%-. The most significant consequences are caused by the prolonged blockage of the duct by a stone, which can produce a persistent ductal dilatation with a swelling that does not subside, and could lead to the complete degeneration of the parenchyma, becoming a hot spot where secondary infections may occur, leading to acute bacterial sialadenitis or glandular abscesses. Treatment options range from a single probing extraction, extraction with sialographic control using the sialoendoscope, LASER intraductal lithotripsy, lithotripsy extracorporeal shock wave (ESWL), to the surgical techniques combining open duct with endoscopic or glandular removal. We propose, with regard to a case, the use of a simple piezoelectric device which, tunnelling through the glandular channel by the ostium, allows stone fragmentation, without damaging the surrounding soft tissue. Stone removal by this less invasive method reduces the need for more complex and expensive techniques. The postoperative course without retraction of the ostium, and the regaining of functionality is favourable. Key words:Calculus, lithotripsy, minimally invasive therapy, piezoelectric surgery, salivary glands, soft tissues. PMID- 25136433 TI - Iatrogenic salivary duct injury in head and neck cancer patients: Report of four cases and review of the literature. AB - INTRODUCTION: The lesions of the salivary ducts may be idiopathic, post- traumatic, or iatrogenic and lead to sialocele formation with persistent painful facial swelling or cutaneous fistula formation. No consensus on treatment of this condition exists: the options of treatment include needle aspiration, pressure dressings, antisialogogue therapy, radiotherapy, botulinum toxin and surgical approaches as duct repair, diversion, ligation, different drainage systems and even parotidectomy/submaxilectomy. The management and special features of iatrogenic salivary duct injury in patients with oral cancer who underwent head and neck reconstructive surgery has not been described yet. MATERIAL AND METHODS: We present four cases of iatrogenic lesions of salivary ducts and its management in patients with oral cancer. CONCLUSIONS: The iatrogenic lesions of salivary ducts are to be taken into account in patients with oral cancer as the distal ends of salivary ducts could be involved in the margins of surgical resection. Different options of treatment of this complication are described. Key words:Sialocele, oral cancer, salivary duct. PMID- 25136435 TI - Parotid gland solitary fibrous tumor with mandibular bone destruction and aggressive behavior. AB - INTRODUCTION: Solitary fibrous tumor is associated with serosal surfaces. Location in the salivary glands is extremely unusual. Extrathoracic tumors have an excellent prognosis associated with their benign clinical behavior. We report an aggressive and recurrent case of this tumor. We review the clinical presentation, inmunohistochemical profiles and therapeutic approaches. CASE REPORT: A 73-years-old woman presented a mass in her right parotid gland. She had a past history of right superficial parotidectomy due to a neurilemoma. FNAB and magnetic resonance were non-specific. After a tumor resection, microscopic findings were spindled tumor cells with reactivity to CD34, bcl-2 and CD99 and the tumor was diagnosed as Solitary Fibrous Tumor. The patient suffered two recurrences and the tumor had a histological aggressive behavior and a destruction of the cortical bone of the mandible adjacent to the mass. A marginal mandibulectomy with an alveolar inferior nerve lateralization was performed. CONCLUSIONS: Solitary fibrous tumor is a very rare tumor. Usually, they are benign, but occasionally they can be aggressive. Complete resection is the most important prognostic factor and no evidence supports the efficacy of any therapy different to surgery. Due to the unknown prognosis and to the small number of cases reported, a long-term follow-up is guaranteed. Key words:Solitary fibrous tumor, parotid mass, parotid gland, salivary gland, rare tumors. PMID- 25136436 TI - Zinsser-Cole-Engmann syndrome: A rare case report with literature review. AB - Zinsser-Cole-Engmann syndrome, more commonly known as Dyskeratosis Congenita, is a heritable genodermatosis having an estimated incidence of 1 in 1 million people. It is important for an oral physician to be aware of this condition as oral leukoplakia occurs in this condition as part of a classic triad along with reticulate skin pigmentation and nail dystrophy. Besides these, there may be myriad multisystem involvement as well. These individuals have a high predilection for developing malignancies as well as other grave life-threatening conditions. Timely diagnosis and management of these cases may help improve their morbidity and mortality, for which oral physicians can play a major role in recognizing the cases. This will only be possible when more of such cases are reported in dental literature. Here we present a case report of a 30 year old male patient who reported to our department with all the characteristic features of the triad and a few additional findings concordant to the disease as well. Key words:Zinsser-Cole-Engmann syndrome, Dyskeratosis Congenita, leukoplakia, genodermatosis, skin pigmentation, nail dystrophy, progeria, hematological disturbances. PMID- 25136437 TI - The craniofacial necrotizing fasciitis after a minor trauma in an elderly white woman. AB - The term necrotizing fasciitis /NF/ was probably first described by Jones in 1871 as "hospital gangrene". NF, with its fast spreading from the local infection to massive necrosis of the underlying tissues, ie. superficial fascia and subcutaneous layers, is a potentially fatal disease, unless diagnosed early and properly treated. NF is more frequent in frail patients with chronic debilitating illnesses, immune deficiencies or from a poor social background. Sixty percent of NF cases occur in females. Here we present a case of necrotizing fasciitis of the head and neck region after a minor trauma (phenol blocks due to severe neuropathic pain) in an 82-year-old female with the history of trigeminal neuralgia. Key words:Necrotizing fasciitis, craniofacial infection, tissue necrosis. PMID- 25136438 TI - Lowering of the mouth floor and vestibuloplasty to support a mandibular overdenture retained by two implants. A case report. AB - In Oral Implantology most of the procedures are predictable and have high success rates. The use of osseointegrated implants as a therapeutic option for the rehabilitation of patients with severe mandibular atrophy has decreased the need for pre-prosthetic surgery Nevertheless, complications may occur during implant surgery and also once the prosthesis has been placed. This paper describes the case of a totally edentulous patient with an upper complete removable denture and an implant-retained overdenture with two implants in the intermentonian region. During clinical examination, the implant abutments were totally covered by soft tissue since the floor of the mouth was elevated. The panoramic radiography showed severe mandibular atrophy. Vestibuloplasty was performed together with the lowering of the floor of the mouth under general anesthesia and nasotracheal intubation to expose the implants. A new prosthesis was fabricated for the patient to prevent recurrence and improve the patient's chewing ability as it formed a physical barrier against soft tissue migration on prosthetic attachments. Key words:Vestibuloplasty, lowering of the mouth floor, complications in oral implantology. PMID- 25136439 TI - Parry Romberg syndrome with localized scleroderma: A case report. AB - Parry Romberg syndrome(PRS) is a rare acquired poorly understood neurocutaneous syndrome of unknown etiology characterized by slow progressive atrophic changes commonly affecting one half of the face. The exact incidence and etiology towards the syndrome remains unclear. Apart from the multifactorial etiology proposed, the possible primary cause is mainly attributed to the cerebral disturbance of the fat metabolism. The syndrome overlaps with "en coup de sabre" morphea, with an ill defined relationship existing between the two. Parry Romberg Syndrome is an invalidating lesion that may be associated with different neurological, cutaneous, ocular, dental and autoimmune abnormalities. This report presents one rare case of 22 years old female patient with Parry Romberg syndrome associated with localized scleroderma, accompanied by a brief review of literature with classical clinical, radiographic, histological findings and the treatment of progressive hemifacial atrophy. Key words:Parry Romberg syndrome, progressive facial hemiatrophy, morphea, localized scleroderma. PMID- 25136440 TI - Traumatic neuroma of the mandible: A case report with spontaneous remission. AB - Traumatic neuroma is a well-known disorder involving peripheral nerves, which occurs following trauma or surgery. The lesion develops most commonly in the soft tissues of the mental foramen area, lower lip and tongue. Intra-osseous lesions arising in jawbones are very uncommon. In this paper, we report a new case of an intra-osseous traumatic neuroma, discovered incidentally on a panoramic radiograph obtained for orthodontic documentation. In addition, the case herein described developed spontaneous remission, a situation not previously reported in the literature. Finally, we discuss relevant demographic, clinical, microscopic, immunohistochemical and treatment aspects of traumatic neuromas. Key words:Amputation neuroma, traumatic neuroma, mandible, spontaneous remission. PMID- 25136442 TI - Editorial. PMID- 25136441 TI - Operational definitions of asthma in recent epidemiological studies are inconsistent. AB - OBJECTIVE: The best combination of questions to define asthma in epidemiological asthma studies is not known. We summarized the operational definitions of asthma used in prevalence studies and empirically assess how asthma prevalence estimates vary depending on the definition used. METHODS: We searched the Thomson Reuters ISI Web of knowledge and included (1) cross-sectional studies (2) on asthma prevalence (3) conducted in the general population and (4) containing an explicit definition of asthma. The search was limited to the 100 most-cited papers or published since January 2010. For each paper, we recorded the asthma definition used and other variables. Then we applied the definitions to the data of the Portuguese National Asthma survey (INAsma) and of the 2005-2006 National Health and Nutrition Examination Survey (NHANES) computing asthma prevalence estimates for the different definitions. RESULTS: Of 1738 papers retrieved, 117 were included for analysis. Lifetime asthma, diagnosed asthma and current asthma were defined in 8, 12 and 29 different ways, respectively. By applying definitions of current asthma on INAsma and NHANES data, the prevalence ranged between 5.3% 24.4% and 1.1%-17.2%, respectively. CONCLUSIONS: There is considerable heterogeneity in the definitions of asthma used in epidemiological studies leading to highly variable estimates of asthma prevalence. Studies to inform a standardized operational definition are needed. Meanwhile, we propose a set of questions to be reported when defining asthma in epidemiological studies. PMID- 25136443 TI - MaxBin: an automated binning method to recover individual genomes from metagenomes using an expectation-maximization algorithm. AB - BACKGROUND: Recovering individual genomes from metagenomic datasets allows access to uncultivated microbial populations that may have important roles in natural and engineered ecosystems. Understanding the roles of these uncultivated populations has broad application in ecology, evolution, biotechnology and medicine. Accurate binning of assembled metagenomic sequences is an essential step in recovering the genomes and understanding microbial functions. RESULTS: We have developed a binning algorithm, MaxBin, which automates the binning of assembled metagenomic scaffolds using an expectation-maximization algorithm after the assembly of metagenomic sequencing reads. Binning of simulated metagenomic datasets demonstrated that MaxBin had high levels of accuracy in binning microbial genomes. MaxBin was used to recover genomes from metagenomic data obtained through the Human Microbiome Project, which demonstrated its ability to recover genomes from real metagenomic datasets with variable sequencing coverages. Application of MaxBin to metagenomes obtained from microbial consortia adapted to grow on cellulose allowed genomic analysis of new, uncultivated, cellulolytic bacterial populations, including an abundant myxobacterial population distantly related to Sorangium cellulosum that possessed a much smaller genome (5 MB versus 13 to 14 MB) but has a more extensive set of genes for biomass deconstruction. For the cellulolytic consortia, the MaxBin results were compared to binning using emergent self-organizing maps (ESOMs) and differential coverage binning, demonstrating that it performed comparably to these methods but had distinct advantages in automation, resolution of related genomes and sensitivity. CONCLUSIONS: The automatic binning software that we developed successfully classifies assembled sequences in metagenomic datasets into recovered individual genomes. The isolation of dozens of species in cellulolytic microbial consortia, including a novel species of myxobacteria that has the smallest genome among all sequenced aerobic myxobacteria, was easily achieved using the binning software. This work demonstrates that the processes required for recovering genomes from assembled metagenomic datasets can be readily automated, an important advance in understanding the metabolic potential of microbes in natural environments. MaxBin is available at https://sourceforge.net/projects/maxbin/. PMID- 25136444 TI - Obstructive sleep apnea and pulmonary function in patients with severe obesity before and after bariatric surgery: a randomized clinical trial. AB - BACKGROUND: The increasing prevalence of obesity in both developed and developing countries is one of the most serious public health problems and has led to a global epidemic. Obesity is one of the greatest risk factors of obstructive sleep apnea (OSA), which is found in 60 to 70% of obese patients mainly due to the buildup of fat tissue in the upper portion of the thorax and neck. The aim of the present randomized clinical trial is to assess daytime sleepiness, sleep architecture and pulmonary function in patients with severe obesity before and after bariatric surgery. METHODS: This randomized, controlled trial, was designed, conducted, and reported in accordance with the standards of The CONSORT (Consolidated Standards of Reporting Trials) Statement. Patients were divided into a bariatric surgery group and control group. The clinical evaluation was performed at the Sleep Laboratory of the Nove de JulhoUniversity (Sao Paulo, Brazil) and consisted of the collection of clinical data, weight, height, body mass index (BMI), measurements of neck and abdomen circumferences, spirometry, maximum ventilatory pressure measurements, standard overnight polysomnography (PSG) and the administration of the Berlin Questionnaire and Epworth Sleepiness Scale. RESULTS: Fifty-two patients participated in the present study and performed PSG. Out of these, 16 underwent bariatric surgery. After surgery, mean BMI decreased from 48.15 +/- 8.58 to 36.91 +/- 6.67 Kg/m(2). Significant differences were found between the preoperative and postoperative periods regarding neck (p < 0.001) and waist circumference (p < 0.001), maximum inspiratory pressure (p = 0.002 and p = 0.004) and maximum expiratory pressure (p = 0.001 and p = 0.002) for women and men, respectively, as well as sleep stage N3 (p < 0.001), REM sleep (p = 0.049) and the apnea-hypopnea index (p = 0.008). CONCLUSIONS: Bariatric surgery effectively reduces neck and waist circumference, increases maximum ventilatory pressures, enhances sleep architecture and reduces respiratory sleep disorders, specifically obstructive sleep apnea, in patients with severe obesity. TRIAL REGISTRATION: THE PROTOCOL FOR THIS STUDY WAS REGISTERED WITH THE WORLD HEALTH ORGANIZATION (UNIVERSAL TRIAL NUMBER: U1111-1121 8873) and Brazilian Registry of Clinical Trials - ReBEC (RBR-9k9hhv). PMID- 25136446 TI - IgG4-related thyroiditis: a case report and review of literature. AB - A 55-year-old male, with a positive medical history for hypothyroidism, treated with stable doses for years was admitted with subacute thyroiditis and a feeling of pain and pressure in the neck. Laboratory tests showed decrease in TSH levels, elevated erythrocyte sedimentation rate, and very high antithyroid antibodies. Owing to enlarging goiter and exacerbation in the patient's complaints, he was operated with excision of a fibrotic and enlarged thyroid lobe. Elevated IgG4 plasma levels and high IgG4/IgG plasma cell ratio on immunohistochemistry led to the diagnosis of IgG4-mediated thyroiditis. We concluded that IgG4-thyroiditis and IgG4-related disease should be considered in all patients with an aggressive form of Hashimoto's thyroiditis. LEARNING POINTS: IgG4-related disease is a systemic disease that includes several syndromes; IgG4-related thyroiditis is one among them.IgG4-thyroiditis should be considered in all patients with an aggressive form of Hashimoto's thyroiditis.Patients with suspected IgG4 thyroiditis should have blood tested for IgG4/IgG ratio and appropriate immunohistochemical staining if possible. PMID- 25136445 TI - Community based interventions for the prevention and control of tuberculosis. AB - In 2012, an estimated 8.6 million people developed tuberculosis (TB) and 1.3 million died from the disease. With its recent resurgence with the human immunodeficiency virus (HIV); TB prevention and management has become further challenging. We systematically evaluated the effectiveness of community based interventions (CBI) for the prevention and treatment of TB and a total of 41 studies were identified for inclusion. Findings suggest that CBI for TB prevention and case detection showed significant increase in TB detection rates (RR: 3.1, 95% CI: 2.92, 3.28) with non-significant impact on TB incidence. CBI for treating patients with active TB showed an overall improvement in treatment success rates (RR: 1.09, 95% CI: 1.07, 1.11) and evidence from a single study suggests significant reduction in relapse rate (RR: 0.26, 95% CI: 0.18, 0.39). The results were consistent for various study design and delivery mechanism. Qualitative synthesis suggests that community based TB treatment delivery through community health workers (CHW) not only improved access and service utilization but also contributed to capacity building and improving the routine TB recording and reporting systems. CBI coupled with the DOTS strategy seem to be an effective approach, however there is a need to evaluate various community-based integrated delivery models for relative effectiveness. PMID- 25136447 TI - Recurrent benign adrenal pheochromocytomas associated with hemihypertrophy. AB - We report a case of a female with hemihypertrophy, who developed five recurrences of pheochromocytomas until the age of 35. Timely follow-up of the patient's blood pressure assisted in early diagnosis and treatment of recurrent tumors. LEARNING POINTS: Recurrent benign pheochromocytomas should raise suspicion of a genetic syndrome.A pheochromocytoma at a young age has a high propensity to recur and strict follow-up is mandatory. PMID- 25136448 TI - A clinically novel AIP mutation in a patient with a very large, apparently sporadic somatotrope adenoma. AB - Heterozygous germline inactivating mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene lead to pituitary adenomas that most frequently present in the setting of familial isolated pituitary adenoma syndrome, usually as somatotropinomas and prolactinomas. More recently, they have been found in a significant percentage of young patients presenting with pituitary macroadenoma without any apparent family history. We describe the case of a 19-year-old man who presented with a gigantic somatotropinoma. His family history was negative. His peripheral DNA showed a heterozygous AIP mutation (p.I13N), while tumor tissue only had the mutated allele, showing loss of heterozygosity (LOH) and suggesting that the mutation caused the disease. LEARNING POINTS: AIP mutations may be observed in sporadic somatotrope adenomas occurring in young patients.LOH is a strong indicator that an AIP variant is disease causing.Somatotrope adenomas in carriers of AIP mutations are generally larger and more difficult to cure. PMID- 25136449 TI - Catecholamine-secreting carotid body paraganglioma: successful preoperative control of hypertension and clinical symptoms using high-dose long-acting octreotide. AB - A 48-year-old hypertensive and diabetic patient presented with a 10-year history of progressive right facial pain, tinnitus, hearing loss, sweating, and palpitations. Investigations revealed a 5.6 cm vascular tumor at the carotid bifurcation. Her blood pressure (BP) was 170/110, on lisinopril 20 mg od and amlodipine 10 mg od and 100 U of insulin daily. A catecholamine-secreting carotid body paraganglioma (CSCBP) was suspected; the diagnosis was confirmed biochemically by determining plasma norepinephrine (NE) level, 89 000 pmol/l, and chromogranin A (CgA) level, 279 MUg/l. Meta-iodobenzylguanidine and octreotide scanning confirmed a single tumor in the neck. A week after giving the patient a trial of octreotide 100 MUg 8 h, the NE level dropped progressively from 50 000 to 25 000 pmol/l and CgA from 279 to 25 MUg/l. Treatment was therefore continued with labetalol 200 mg twice daily (bid) and long-acting octreotide-LA initially using 40 mg/month and later increasing to 80 mg/month. On this dose and with a reduced labetalol intake of 100 mg bid, BP was maintained at 130/70 and her symptoms resolved completely. CgA levels returned to normal in the first week and these were maintained throughout the 3 month treatment period. During tumor resection, there were minimal BP fluctuations during the 10 h procedure. We conclude that short-term high-dose octreotide-LA might prove valuable in the preoperative management of catecholamine-secreting tumors. To the best of our knowledge, this is the first report on the successful use of octreotide in a CSCBP. LEARNING POINTS: The value of octreotide scanning in the localization of extra-adrenal pheochromocytoma.Control of catecholamine secretion using high-dose octreotide.This is a report of a rare cause of secondary diabetes and hypertension. PMID- 25136450 TI - Contribution of antimicrobial stewardship programs to reduction of antimicrobial therapy costs in community hospital with 429 Beds --before-after comparative two year trial in Japan. AB - OBJECTIVES: Do antimicrobial stewardship programs (ASPs) contribute to reduction of antimicrobial therapy costs in Japanese community hospitals? To answer this health economic question, a before-after comparative two-year trial in a community hospital in the country was designed. METHODS: The study was conducted at National Hospital Organization Tochigi Medical Center, a community hospital with 429 beds. We compared six-month period before-ASP (January 2010 to June 2010) and 24-month period after ASP (July 2010 to June 2012) in primary and secondary outcome measures. Three medical doctors, three pharmacists and two microbiology technologists participate in the ASPs. The team then provided recommendations based on the supplemental elements to primary physicians who prescribed injectable antimicrobials. Prospective audit with intervention and feedback was applied in the core strategy while dose optimization, de-escalation and recommendations for alternate agents and blood cultures were applied in the supplemental elements. The primary outcome was measured by the antimicrobial therapy costs (USD per 1,000 patient-days), while the secondary outcomes included the amount of antimicrobials used (defined daily doses per 1,000 patient-days), sensitivity rates (%) of Pseudomonas aeruginosa (P. aeruginosa) to Meropenem (MEPM), Ciprofloxacin (CPFX) and Amikacin (AMK), length of stay (days) and detection rates (per 1,000 patient-day) of methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase-producing organisms (ESBLs) through blood cultures. RESULTS: In the study, recommendations were made for 465 cases out of 1,427 cases subject to the core strategy, and recommendations for 251 cases (54.0%) were accepted. After ASP, the antimicrobial therapy costs decreased by 25.8% (P = 0.005) from those before ASP. Among the secondary outcomes, significant changes were observed in the amount of aminoglycosides used, which decreased by 80.0% (P < 0.001) and the detection rate of MRSA, which decreased by 48.3% (P < 0.001). CONCLUSIONS: The study suggested the possibility that ASPs contributed to the reduction of the antimicrobial therapy costs in a community hospital with 429 beds. PMID- 25136451 TI - The creation of pollution mapping and measurement of ambient concentration of sulfur dioxide and nitrogen dioxide with passive sampler. AB - BACKGROUND: Measurements of nitrogen and sulfur dioxide using passive sampler over 12 months in Samsun, Turkey, are compared with SO2 and NO2 concentrations obtained from a co-located chemiluminescence analyzer. The concentrations of Sulfur and nitrogen dioxide in the ambient air during the period from November 2009 to September 2010 are analyzed. RESULTS: The highest value for annual NO2 and SO2 averages of passive sampler was 29.65 MUg/m(3) and 21.01 MUg/m(3) for exposures of 2-weeks at an industrial site. The maximum monthly concentration for SO2 was observed at the 10(th) measurement station with 44.19 MUg/m(3) for August. The maximum monthly concentration for NO2 was observed on the 3(rd) measurement station with 42.83 MUg/m(3) for November. A negative correlation between nitrogen dioxide concentrations and temperature (R(2) = -0.5489) was estimated. A positive correlation between nitrogen dioxide measurement with passive sampler and continuous measurement (R(2) = 0.6571) was estimated. PMID- 25136452 TI - The effects of intravitreal bevacizumab in infectious and noninfectious uveitic macular edema. AB - Background/Aims. To assess the effect of intravitreal bevacizumab injection (IVBI) for the treatment of macular edema due to infectious and noninfectious uveitides. Design. Retrospective interventional case series. Methods. A chart review was performed on all the patients who were diagnosed with uveitic macular edema (UME) and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi Arabia. All included patients had their visual acuity and macular thickness analyzed at baseline and at 1 and 3 months following IVBI and any sign of reactivation was noted. Results. The mean age of patients was 41 +/- 16 years with a mean followup of 4 +/- 1 months. Ten patients had idiopathic intermediate uveitis, 9 patients had Behcet's disease, 10 had idiopathic panuveitis, and twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the mean LogMAR visual acuity improved from 0.8 +/- 0.8 at baseline to 0.4 +/- 0.5 at 1 month and 0.3 +/- 0.5 at 3 months (P < 0.002, at 3 months). The mean macular thickness was 430 +/- 132 MUm at baseline. Following IVBI macular thickness improved to 286 +/- 93 MUm at 1 month and to 265 +/- 88 MUm at 3 months of followup (P < 0.001, at 3 months). Conclusion. Bevacizumab was effective in the management of UME associated with both infectious and noninfectious uveitides. Intravitreal bevacizumab induced remission of UME with infectious uveitis and had no immunosuppressive effect against infectious agents. PMID- 25136453 TI - Evaluation of the Repeatability and the Reproducibility of AL-Scan Measurements Obtained by Residents. AB - Purpose. To assess the repeatability and reproducibility of ocular biometry and intraocular lens (IOL) power measurements obtained by ophthalmology residents using an AL-Scan device, a novel optical biometer. Methods. Two ophthalmology residents were instructed regarding the AL-Scan device. Both performed ocular biometry and IOL power measurements using AL-Scan, three times on each of 128 eyes, independently of one another. Corneal keratometry readings, horizontal iris width, central corneal thickness, anterior chamber depth, pupil size, and axial length values measured by both residents were recorded together with IOL power values calculated on the basis of four different IOL calculation formulas (SRK/T, Holladay, and HofferQ). Repeatability and reproducibility of the measurements obtained were analyzed using the intraclass correlation coefficient (ICC). Results. Repeatability (ICC, 0.872-0.999 for resident 1 versus 0.905-0.999 for resident 2) and reproducibility (ICC, 0.916-0.999) were high for all biometric measurements. Repeatability (ICC, 0.981-0.983 for resident 1 versus 0.995-0.996 for resident 2) and reproducibility were also high for all IOL power measurements (ICC, 0.996 for all). Conclusions. The AL-Scan device exhibits good repeatability and reproducibility in all biometric measurements and IOL power calculations, independent of the operator concerned. PMID- 25136454 TI - Correlation between Intraocular Pressure Fluctuation with Postural Change and Postoperative Intraocular Pressure in Relation to the Time Course after Trabeculectomy. AB - Background. To investigate the correlation between intraocular pressure (IOP) fluctuation with postural change and IOP in relation to the time course after trabeculectomy. Methods. A total of 29 patients who had previously undergone primary trabeculectomy with mitomycin C were examined. IOP was obtained at 1, 2, 3, 6, and 12 months and then every 6 months postoperatively. Results. The postural IOP difference before surgery was 3.0 +/- 1.8 mmHg, which was reduced to 0.9 +/- 1.1 mmHg at 1 month, 1.0 +/- 1.0 mmHg at 2 months, 1.3 +/- 2.0 mmHg at 3 months, 1.3 +/- 1.4 mmHg at 6 months, 1.4 +/- 1.5 mmHg at 12 months, and 1.1 +/- 0.7 mmHg at 18 months after trabeculectomy (P < 0.01 each visit). The filtering surgery failed in 7 out of 29 eyes. Postural IOP changes were less than 3 mmHg in those patients who did not require needle revision at every visit. However, in patients who did require needle revision, the increase in the posture-induced IOP was greater than 3 mmHg prior to the increase in the sitting position IOP. Conclusions. Assessment of postural IOP changes after trabeculectomy might be potentially useful for predicting IOP changes after trabeculectomy. PMID- 25136455 TI - Gender and uveitis. PMID- 25136456 TI - Spectrum of Histomorphologic Findings in Liver in Patients with SLE: A Review. AB - Collagen vascular diseases (CVDs) like systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren syndrome (SS), and scleroderma are immunologically mediated disorders that typically have multisystem involvement. Although clinically significant liver involvement is rare, liver enzyme abnormalities are common in these patients. The reported prevalence of hepatic involvement in SLE, histopathologic findings, and its significance is very variable in the existing literature. It is important to be familiar with the causes of hepatic involvement in SLE along with histomorphological features which aid in distinguishing hepatitis of SLE from other hepatic causes as they would alter the patient management and disease course. Histopathology of liver in SLE shows a wide morphological spectrum commonly due to a coexisting pathology. Drug induced hepatitis, viral etiology, and autoimmune overlap should be excluded before attributing the changes to SLE itself. Common histopathologic findings in SLE include fatty liver, portal inflammation, and vascular changes like hemangioma, congestion, nodular regenerative hyperplasia, arteritis, and abnormal vessels in portal tracts. PMID- 25136457 TI - Latency after preterm prelabor rupture of the membranes: increased risk for periventricular leukomalacia. AB - OBJECTIVE: To identify the risk factors for cystic periventricular leukomalacia (cPVL) and their implications for deciding between immediate delivery and conservative management of preterm prelabor rupture of the membranes (pPROM). METHODS: The following risk factors were compared between cPVL infants and 6440 controls: chorioamnionitis, sex, gestational age (GA), birth weight, pPROM, and pPROM-delivery interval. Factor impact on cPVL risk and clinical decision-making was determined by multivariate logistic regression. RESULTS: Overall cPVL prevalence (n = 32) was 0.99/1000 births. All cPVL infants but one were born <34 weeks of gestation and were <2500 g; 56% had histological chorioamnionitis versus 1.1% of controls (OR 35.9; 95%-CI 12.6-102.7). Because chorioamnionitis is a postnatal diagnosis, logistic regression was performed with prenatally available factors: pPROM-delivery interval >48 hours (OR 9.0; 95%-CI 4.1-20.0), male gender (OR 3.2; 95%-CI 1.4-7.3). GA was not a risk factor if birth weight was included. Risk decreased with increasing fetal weight despite a prolonged pPROM-delivery interval. CONCLUSION: pPROM-delivery interval is the single most important prenatally available risk factor for the development of cPVL. Immediate delivery favors babies with chorioamnionitis but disfavors those with non infectious pPROM. In the absence of clinical chorioamnionitis fetal weight gain may offset the inflammatory risk of cPVL caused by a prolonged pPROM-delivery interval. PMID- 25136458 TI - Locally advanced and unresectable cutaneous squamous cell carcinoma: outcomes of concurrent cetuximab and radiotherapy. AB - Background. Advanced age and immune dysfunction are risk factors for cutaneous squamous cell carcinoma (cSCC) and often render patients with locally-advanced disease medically inoperable or surgically unresectable, but potentially curable with radiotherapy. Concurrent chemotherapy and radiotherapy may not be well tolerated in this population, but another systemic therapy may improve disease control. Objective. Determine the tolerance and efficacy of concurrent cetuximab and radiotherapy (CRT) for patients with locally advanced and unresectable cSCC. Methods. Retrospective analysis of 12 patients treated with CRT for locally advanced and unresectable cSCC. Results. Patients were elderly and 75% had moderate-to-severe comorbidities, while 42% had immune dysfunction. Grades 3-4 adverse events were noted in 83% of patients; 67% required hospital admission for adverse events. Complete and partial response was noted in 36% and 27% (response rate, 64%). Stable and progressive disease was noted in 3 and 1 patients, respectively (disease control rate, 91%). Median progression-free and overall survival were 6.4 and 8.0 months, respectively. Limitations. Retrospective small cohort, single-institution analysis. Conclusion. Patients selected for CRT were elderly, with comorbidities and immune dysfunction, but treatment responses were observed. Patients selected for this treatment approach have a poor prognosis with limited capacity for therapy; more effective treatment is needed. PMID- 25136459 TI - Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C. AB - The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9) levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C) with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (DeltaLDL-C: 2.6 +/- 11.4%) were compared to age- and gender-matched atorvastatin responders (DeltaLDL-C: 50.7 +/- 8.5%) and placebo-treated subjects (DeltaLDL-C: 9.9 +/- 21.5%). Free PCSK9 was marginally higher in nonresponders at baseline (P = 0.07) and significantly higher in atorvastatin responders after 6 months of treatment (P = 0.04). The change in free PCSK9 over 6 months with statin treatment was higher (P < 0.01) in atorvastatin responders (134.2 +/- 131.5 ng/mL post- versus prestudy) than in either the nonresponders (39.9 +/- 87.8 ng/mL) or placebo subjects (27.8 +/- 97.6 ng/mL). Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment. PMID- 25136460 TI - Physicochemical characteristics of citrus seed oils from kerman, iran. AB - Recently, there has been a great deal of attention on usage, byproducts, and wastes of the food industry. There have been many studies on the properties of citrus seeds and extracted oil from citrus grown in Kerman, Iran. The rate of oil content of citrus seeds varies between 33.4% and 41.9%. Linoleic acid (33.2% to 36.3%) is the key fatty acid found in citrus seeds oil and oleic (24.8% to 29.3%) and palmitic acids (23.5% to 29.4%) are the next main fatty acids, respectively. There are also other acids found at trivial rates such as stearic, palmitoleic, and linolenic. With variation between 0.54 meg/kg and 0.77 mgq/kg in peroxide values of citrus seed oils, acidity value of the oil varies between 0.44% and 0.72%. The results of the study showed that citrus seeds under study (orange and sour lemon grown in Kerman province) and the extracted oil have the potential of being used as the source of edible oil. PMID- 25136462 TI - Nephrotic syndrome secondary to proliferative glomerulonephritis with monoclonal immunoglobulin deposits of lambda light chain. AB - We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function. Work-up for both autoimmune and infectious diseases and hematologic malignancies including multiple myeloma were negative. Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID). The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent. PMID- 25136463 TI - Sigmoid colon migration of an intrauterine device. AB - Background. Intrauterine devices (IUD) are commonly used birth control methods. Colonic perforation is an infrequent but serious complication of IUD. Case. A 34 year-old woman with 2-years history of IUD, inserted at early puerperal period, presented to gynecologist with chronic pelvic pain and dyspareunia. Radiological assessment revealed that there were two copper-T devices: one in uterine cavity and another in the colonic lumen. Attempts of retrieval with colonoscopy and laparoscopy were unsuccessful. Intrauterine device embedded in sigmoid colon wall was removed with resection of the involved segment and primary anastomosis was performed. Conclusion. Although there are cases in literature that are successfully managed with colonoscopy, in chronic cases, formation of granulation tissue complicates retrieval of an IUD by this intervention. PMID- 25136461 TI - Management of humeral and glenoid bone loss in recurrent glenohumeral instability. AB - Recurrent shoulder instability and resultant glenoid and humeral head bone loss are not infrequently encountered in the population today, specifically in young, athletic patients. This review on the management of bone loss in recurrent glenohumeral instability discusses the relevant shoulder anatomy that provides stability to the shoulder joint, relevant history and physical examination findings pertinent to recurrent shoulder instability, and the proper radiological imaging choices in its workup. Operative treatments that can be used to treat both glenoid and humeral head bone loss are outlined. These include coracoid transfer procedures and allograft/autograft reconstruction at the glenoid, as well as humeral head disimpaction/humeroplasty, remplissage, humeral osseous allograft reconstruction, rotational osteotomy, partial humeral head arthroplasty, and hemiarthroplasty on the humeral side. Clinical outcomes studies reporting general results of these techniques are highlighted. PMID- 25136464 TI - Vaginal septoplasty in septate uterus with double cervix. AB - Fusion defects of the Mullerian ducts occur frequently and they have been described by the American Fertility Society. However, septate uterus with cervical duplication and longitudinal vaginal septum is not described by this classification and has suggested a change in the classical theory of fusion of the Mullerian ducts. This paper describes a rare case report of a patient with complete septate uterus with double cervix and longitudinal vaginal septum, submitted to the vaginal septoplasty for dyspareunia, progressing to clinical improvement. The description of this case is to contribute with all uncommon cases of Mullerian anomalies reports and clinical treatment protocols, which is not yet established. PMID- 25136465 TI - Successful laparoscopic management of ruptured tubal pregnancy with an ipsilateral ectopic pelvic kidney. AB - Objective. To report a case of successful laparoscopic management of a left ruptured tubal pregnancy in the setting of an ipsilateral ectopic pelvic kidney. Method. Case report was prepared at Wayne State University/Detroit Medical Center. The patient is a young woman gravida 2 para 0 in her twenties who presented with severe abdominal pain and vaginal bleeding. She had a plateaued beta HCG and ultrasonographic findings suggestive of ectopic left tubal pregnancy along with an ectopic ipsilateral pelvic kidney. The IRB approval is not needed, as this is a case report. The informed consent could not be obtained, as the patient was not reachable. Result. Multiple intraperitoneal adhesions, left ruptured ampullary ectopic pregnancy and left retroperitoneal pelvic mass consistent with ipsilateral ectopic pelvic kidney. Conclusion. Laparoscopic management of tubal pregnancy can be safely performed in the setting of an ipsilateral ectopic pelvic kidney. PMID- 25136466 TI - Mayer-rokitansky-kuster-hauser syndrome associated with severe inferior vena cava stenosis. AB - Precis. The postoperative course of a neovagina creation procedure in a young woman with Meyer-Rokitansky-Kuster-Hauser syndrome was complicated, despite prophylaxis, by extensive pelvic deep venous thrombosis secondary to unsuspected severe inferior vena cava stenosis. Background. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by congenital vaginal agenesis and an absent or rudimentary uterus in genotypical females. Malformations of the inferior vena cava (IVC) are not commonly associated with MRKH syndrome. We report a case of a patient with MRKH syndrome with severe IVC stenosis that was diagnosed when the patient presented with extensive pelvic deep venous thrombosis (DVT) during the postoperative course of a neovagina creation. Case. A 19-year-old female underwent a McIndoe procedure. Despite DVT prophylaxis, extensive pelvic DVT of the femoral vein was diagnosed on postoperative day 7. Therapeutic anticoagulation was initiated, and pharmacological and mechanical thrombolysis were performed. During these procedures, a hypoplastic IVC was noted. Conclusion. MRKH syndrome can be associated with IVC malformations, which constitute an anatomical risk factor for postoperative DVT. PMID- 25136467 TI - Maintenance therapy with trastuzumab in her2 positive metastatic parotid ductal adenocarcinoma. AB - Salivary ductal carcinomas (SDCs) are extremely rare and aggressive malignancies, accounting for approximately 6% of all salivary gland malignancies. One distinct feature is their resemblance to ductal carcinomas of breast. A significant percentage of SDCs overexpress Her2 and the use of targeted therapy with trastuzumab can be considered in these patients. We report a rare case of long term disease control with trastuzumab in Her2 positive metastatic parotid ductal carcinoma. Our case also highlights that isolated brain metastasis should be managed aggressively to allow optimal local control when systemic disease is under remission with trastuzumab. We have also reviewed the published literature on the use of trastuzumab in SDCs. PMID- 25136468 TI - Myasthenia gravis-like syndrome presenting as a component of the paraneoplastic syndrome of lung adenocarcinoma in a nonsmoker. AB - Adenocarcinoma of the lung is the most common form of lung cancer in nonsmokers. It is commonly seen in the periphery of the lungs. Myasthenia gravis is generally associated with mediastinal malignancies and rarely associated with adenocarcinoma of the lung. We present a case of a 38-year-old male nonsmoker with rapidly progressive adenocarcinoma of the lung associated with myasthenia gravis, a patient whom expired within 27 days of hospital admission and diagnosis. PMID- 25136469 TI - Intra-articular osteoid osteoma mimicking juvenile arthritis. AB - In case of intra-articular osteoid osteoma, misdiagnosis as juvenile arthritis may occur, delaying adequate treatment. We report cases of intra-articular osteoid osteomas in children that were misdiagnosed and initially inappropriately treated with intra-articular corticoid injection. Diagnosis of osteoid osteoma was finally given by CT-scan and appropriate treatment by radiofrequency ablation or surgical ablation was performed. Clinicians and radiologists should be aware of the potentially confusing clinical and imaging findings associated with intra articular osteoid osteoma. PMID- 25136470 TI - Hyperammonemic Encephalopathy due to Valproic Acid and Topiramate Interaction. AB - Valproic acid-induced hyperammonemic encephalopathy is a rare yet serious adverse drug reaction. Medication interactions such a valproic acid and topiramate can precipitate an event. We present the case of a 52-year-old female that presented with acute mental status change and hypersomnolence due to hyperammonemia caused by a valproic acid derivative. The patient improved after withdrawal of the offending medications and treatment with lactulose. Clinicians should remain hypervigilant in monitoring for valproic acid-induced hyperammonemic encephalopathy and risk factors such as polypharmacy. PMID- 25136471 TI - Subcutaneous emphysema, pneumomediastinum, pneumoretroperitoneum, and pneumoscrotum: unusual complications of acute perforated diverticulitis. AB - Pneumomediastinum, and subcutaneous emphysema usually result from spontaneous alveolar wall rupture and, far less commonly, from disruption of the upper airways or gastrointestinal tract. Subcutaneous neck emphysema, pneumomediastinum, and retropneumoperitoneum caused by nontraumatic perforations of the colon have been infrequently reported. The main symptoms of spontaneous subcutaneous emphysema are swelling and crepitus over the involved site; further clinical findings in case of subcutaneous cervical and mediastinal emphysema can be neck and chest pain and dyspnea. Radiological imaging plays an important role to achieve the correct diagnosis and extension of the disease. We present a quite rare case of spontaneous subcutaneous cervical emphysema, pneumomediastinum, and pneumoretroperitoneum due to perforation of an occult sigmoid diverticulum. Abdomen ultrasound, chest X-rays, and computer tomography (CT) were performed to evaluate the free gas extension and to identify potential sources of extravasating gas. Radiological diagnosis was confirmed by the subsequent surgical exploration. PMID- 25136472 TI - Forgotten Kirschner wire causing severe hematuria. AB - Kirschner wire (K-wire) is commonly used in the treatment of hip fracture and its migration into pelvis leading to bladder injury is a very rare complication. Nonremoval of these devices either because of lack of followup or because of prolonged requirement due to disease process is associated with this complication. We report a case of a patient who presented with acute onset severe hematuria with clot retention secondary to perforation of bladder by a migrated K wire placed earlier, for the treatment of hip fracture. Initial imaging showed its presence in the soft tissues of the pelvis away from the major vascular structures. Patient was taken for emergency laparotomy and wire was removed after cystotomy. Postoperative period was uneventful and patient was discharged in satisfactory condition. K-wires are commonly used in the management of fracture bones and their migration has been reported in the literature although such migration in the intrapelvic region involving bladder is very rare. Early diagnosis and prompt removal of such foreign bodies are required to avert potentially fatal involvement of major structures. PMID- 25136473 TI - Effects of whole body vibration and resistance training on bone mineral density and anthropometry in obese postmenopausal women. AB - Objective. The aim of this study was to evaluate the impact of two exercise programs, whole body vibration and resistance training on bone mineral density (BMD) and anthropometry in obese postmenopausal women. Material and Methods. Eighty Egyptian obese postmenopausal women were enrolled in this study; their age ranged from 50 to 68 years. Their body mass index ranged (30-36 kg/m(2)). The exercise prescription consisted of whole body vibration (WBV) and resistance training. Bone mineral density (BMD) and anthropometrical parameters were measured at the beginning and at the end of the study. Changes from baseline to eight months in BMD and anthropometric parameters were investigated. Results. BMD at the greater trochanter, at ward's triangle, and at lumbar spine were significantly higher after physical training, using both WBV and resistive training. Moreover, both exercise programs were effective in BMI and waist to the hip ratio. Simple and multiple regression analyses showed significant associations between physical activity duration and BMD at all sites. The highest values of R (2) were found for the models incorporating WBV plus BMI. Conclusion. The study suggests that both types of exercise modalities had a similar positive effect on BMD at all sites in obese postmenopausal women. Significant association was noted between physical activity and anthropometric variables and BMD measures at all sites. PMID- 25136474 TI - Executive function and postural instability in people with Parkinson's disease. AB - The specific aspects of cognition contributing to balance and gait have not been clarified in people with Parkinson's disease (PD). Twenty PD participants and twenty age- and gender-matched healthy controls were assessed on cognition and clinical mobility tests. General cognition was assessed with the Mini Mental State Exam and Addenbrooke's Cognitive Exam. Executive function was evaluated using the Trail Making Tests (TMT-A and TMT-B) and a computerized cognitive battery which included a series of choice reaction time (CRT) tests. Clinical gait and balance measures included the Tinetti, Timed Up & Go, Berg Balance, and Functional Reach tests. PD participants performed significantly worse than the controls on the tests of cognitive and executive function, balance, and gait. PD participants took longer on Trail Making Tests, CRT-Location, and CRT-Colour (inhibition response). Furthermore, executive function, particularly longer times on CRT-Distracter and greater errors on the TMT-B, was associated with worse balance and gait performance in the PD group. Measures of general cognition were not associated with balance and gait measures in either group. For PD participants, attention and executive function were impaired. Components of executive function, particularly those involving inhibition response and distracters, were associated with poorer balance and gait performance in PD. PMID- 25136475 TI - The therapeutic effect of zuogui wan in gestational diabetes mellitus rats. AB - In this experiment, we established an animal model of gestational diabetes mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats in 1-19d were divided into three groups: (1) Zuogui Wan gestational diabetes mellitus group (group I, n = 12), (2) gestational diabetes mellitus rats as the control group (group II, n = 11), and (3) rats of normal pregnancy group (group III, n = 11). Compared with gestational diabetes mellitus rats as the control group, Zuogui Wan can change the indexes of fasting blood glucose, body weight, total cholesterol, insulin, and metabolism cage index significantly in Zuogui Wan gestational diabetes mellitus group. We can conclude that Zuogui Wan has the therapeutic effect on gestational diabetes mellitus. PMID- 25136476 TI - Night-time decibel hell: mapping noise exposure zones and individual annoyance ratings in an urban environment in ghana. AB - Although accumulating evidence over the past thirty years indicates that noise is an environmental stressor in residential settings, much of the data emanated from studies in high-intensity, noise impact zones around airports or major roads. Little is known about religious noise, especially at night, which is increasingly a growing concern for both the general public and policy-makers in sub-Saharan Africa. Using geographical information systems (GIS), this study measured and mapped exposure to religious noise in a rapidly urbanising municipality in Ghana. Quantitative noise risk assessment was used to evaluate the risk of religious noise-induced hearing loss to residents in the exposed neighbourhoods. The results show that all neighbourhoods where churches were situated had at least one location with significant risk of noise-induced hearing loss. However, there was no statistically significant relationship between neighbourhoods where religious noise exposure was the highest and where noise annoyance was the highest. The magnitude of the noise values for night-time exposure is remarkable particularly given that excessive night-time noise exposure has the greatest detrimental effect on public health. There is the need to focus on vulnerable groups, sensitive hours of the night, and possible confounding with air pollution in order to wholly address this potential hazard. PMID- 25136477 TI - Joint iris boundary detection and fit: a real-time method for accurate pupil tracking. AB - A range of applications in visual science rely on accurate tracking of the human pupil's movement and contraction in response to light. While the literature for independent contour detection and fitting of the iris-pupil boundary is vast, a joint approach, in which it is assumed that the pupil has a given geometric shape has been largely overlooked. We present here a global method for simultaneously finding and fitting of an elliptic or circular contour against a dark interior, which produces consistently accurate results even under non-ideal recording conditions, such as reflections near and over the boundary, droopy eye lids, or the sudden formation of tears. The specific form of the proposed optimization problem allows us to write down closed analytic formulae for the gradient and the Hessian of the objective function. Moreover, both the objective function and its derivatives can be cast into vectorized form, making the proposed algorithm significantly faster than its closest relative in the literature. We compare methods in multiple ways, both analytically and numerically, using real iris images as well as idealizations of the iris for which the ground truth boundary is precisely known. The method proposed here is illustrated under challenging recording conditions and it is shown to be robust. PMID- 25136478 TI - Trapping of a single DNA molecule using nanoplasmonic structures for biosensor applications. AB - Conventional optical trapping using a tightly focused beam is not suitable for trapping particles that are smaller than the diffraction limit because of the increasing need of the incident laser power that could produce permanent thermal damages. One of the current solutions to this problem is to intensify the local field enhancement by using nanoplasmonic structures without increasing the laser power. Nanoplasmonic tweezers have been used for various small molecules but there is no known report of trapping a single DNA molecule. In this paper, we present the trapping of a single DNA molecule using a nanohole created on a gold substrate. Furthermore, we show that the DNA of different lengths can be differentiated through the measurement of scattering signals leading to possible new DNA sensor applications. PMID- 25136479 TI - Self-referenced spectroscopy using plasmon waveguide resonance biosensor. AB - A plasmon waveguide resonance (PWR) sensor is designed, fabricated, and tested for self-referenced biosensing. The PWR sensor is able to support two different polarizations, TM and TE. The TM polarization has a large sensitivity to variations in the background refractive index while the TE polarization is more sensitive to the surface properties. The ability of the PWR sensor to simultaneously operate in both TM and TE modes is used to decouple the background index variations (bulk effects) from the changes in adlayer thickness (surface effects) via multimode spectroscopy. To benchmark the performance of the PWR, a conventional surface plasmon resonance (SPR) sensor is fabricated and tested under the same conditions. PMID- 25136480 TI - Photothermal tomography for the functional and structural evaluation, and early mineral loss monitoring in bones. AB - Salient features of a new non-ionizing bone diagnostics technique, truncated correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade contrast and capable of resolving the trabecular network in three dimensions through the cortical region with and without a soft-tissue overlayer are presented. The absolute nature and early demineralization-detection capability of a marker called thermal wave occupation index, estimated using the proposed modality, have been established. Selective imaging of regions of a specific mineral density range has been demonstrated in a mouse femur. The method is maximum-permissible-exposure compatible. In a matrix of bone and soft-tissue a depth range of ~3.8 mm has been achieved, which can be increased through instrumental and modulation waveform optimization. Furthermore, photoacoustic microscopy, a comparable modality with TC-PCT, has been used to resolve the trabecular structure and for comparison with the photothermal tomography. PMID- 25136481 TI - Gender-related effects of prefrontal cortex connectivity: a resting-state functional optical tomography study. AB - The prefrontal cortex (PFC) is thought to play an important role in "higher" brain functions such as personality and emotion that may associated with several gender-related mental disorders. In this study, the gender effects of functional connectivity, cortical lateralization and significantly differences in the PFC were investigated by using resting-state functional optical tomography (fOT) measurement. A total of forty subjects including twenty healthy male and twenty healthy female adults were recruited for this study. In the results, the hemoglobin responses are higher in the male group. Additionally, male group exhibited the stronger connectivity in the PFC regions. In the result of lateralization, leftward dominant was observed in the male group but bilateral dominance in the female group. Finally, the 11 channels of the inferior PFC regions (corresponding to the region of Brodmann area 45) are significant different with spectrum analysis. Our findings suggest that the resting-state fOT method can provide high potential to apply to clinical neuroscience for several gender-related mental disorders diagnosis. PMID- 25136482 TI - Fast wide-field photothermal and quantitative phase cell imaging with optical lock-in detection. AB - We present a fast, wide-field holography system for detecting photothermally excited gold nanospheres with combined quantitative phase imaging. An interferometric photothermal optical lock-in approach (POLI) is shown to improve SNR for detecting nanoparticles (NPs) on multiple substrates, including a monolayer of NPs on a silanized coverslip, and NPs bound to live cells. Furthermore, the set up allowed for co-registered quantitative phase imaging (QPI) to be acquired in an off-axis holographic set-up. An SNR of 103 was obtained for NP-tagging of epidermal growth factor receptor (EGFR) in live cells with a 3 second acquisition, while an SNR of 47 was seen for 20 ms acquisition. An analysis of improvements in SNR due to averaging multiple frames is presented, which suggest that residual photothermal signal can be a limiting factor. The combination of techniques allows for high resolution imaging of cell structure via QPI with the ability to identify receptor expression via POLI. PMID- 25136483 TI - Nonlinear structured-illumination enhanced temporal focusing multiphoton excitation microscopy with a digital micromirror device. AB - In this study, the light diffraction of temporal focusing multiphoton excitation microscopy (TFMPEM) and the excitation patterning of nonlinear structured illumination microscopy (NSIM) can be simultaneously and accurately implemented via a single high-resolution digital micromirror device. The lateral and axial spatial resolutions of the TFMPEM are remarkably improved through the second order NSIM and projected structured light, respectively. The experimental results demonstrate that the lateral and axial resolutions are enhanced from 397 nm to 168 nm (2.4-fold) and from 2.33 MUm to 1.22 MUm (1.9-fold), respectively, in full width at the half maximum. Furthermore, a three-dimensionally rendered image of a cytoskeleton cell featuring ~25 nm microtubules is improved, with other microtubules at a distance near the lateral resolution of 168 nm also able to be distinguished. PMID- 25136484 TI - Development of a luminous textile for reflective pulse oximetry measurements. AB - In this paper, a textile-based sensing principle for long term photopletysmography (PPG) monitoring is presented. Optical fibers were embroidered into textiles such that out-coupling and in-coupling of light was possible. The "light-in light-out" properties of the textile enabled the spectroscopic characterization of human tissue. For the optimization of the textile sensor, three different carrier fabrics and different fiber modifications were compared. The sample with best light coupling efficiency was successfully used to measure heart rate and SpO2 values of a subject. The latter was determined by using a modified Beer-Lambert law and measuring the light attenuation at two different wavelengths (632 nm and 894 nm). Moreover, the system was adapted to work in reflection mode which makes the sensor more versatile. The measurements were additionally compared with commercially available system and showed good correlation. PMID- 25136485 TI - Characterization and in-vivo evaluation of a multi-resolution foveated laparoscope for minimally invasive surgery. AB - The state-of-the-art laparoscope lacks the ability to capture high-magnification and wide-angle images simultaneously, which introduces challenges when both close up views for details and wide-angle overviews for orientation are required in clinical practice. A multi-resolution foveated laparoscope (MRFL) which can provide the surgeon both high-magnification close-up and wide-angle images was proposed to address the limitations of the state-of-art surgical laparoscopes. In this paper, we present the overall system design from both clinical and optical system perspectives along with a set of experiments to characterize the optical performances of our prototype system and describe our preliminary in-vivo evaluation of the prototype with a pig model. The experimental results demonstrate that at the optimum working distance of 120mm, the high-magnification probe has a resolution of 6.35lp/mm and image a surgical area of 53 * 40mm(2); the wide-angle probe provides a surgical area coverage of 160 * 120mm(2) with a resolution of 2.83lp/mm. The in-vivo evaluation demonstrates that MRFL has great potential in clinical applications for improving the safety and efficiency of the laparoscopic surgery. PMID- 25136486 TI - Improving high resolution retinal image quality using speckle illumination HiLo imaging. AB - Retinal image quality from flood illumination adaptive optics (AO) ophthalmoscopes is adversely affected by out-of-focus light scatter due to the lack of confocality. This effect is more pronounced in small eyes, such as that of rodents, because the requisite high optical power confers a large dioptric thickness to the retina. A recently-developed structured illumination microscopy (SIM) technique called HiLo imaging has been shown to reduce the effect of out-of focus light scatter in flood illumination microscopes and produce pseudo-confocal images with significantly improved image quality. In this work, we adopted the HiLo technique to a flood AO ophthalmoscope and performed AO imaging in both (physical) model and live rat eyes. The improvement in image quality from HiLo imaging is shown both qualitatively and quantitatively by using spatial spectral analysis. PMID- 25136487 TI - Optimized approaches for optical sectioning and resolution enhancement in 2D structured illumination microscopy. AB - The use of structured illumination in fluorescence microscopy allows the suppression of out of focus light and an increase in effective spatial resolution. In this paper we consider different approaches for reconstructing 2D structured illumination images in order to combine these two attributes, to allow fast, optically sectioned, superresolution imaging. We present a linear reconstruction method that maximizes the axial frequency extent of the combined 2D structured illumination passband along with an empirically optimized approximation to this scheme. These reconstruction methods are compared to other schemes using structured illumination images of fluorescent samples. For sinusoidal excitation at half the incoherent cutoff frequency we find that removing information in the zero order passband except for a small region close to the excitation frequency, where it replaces the complementary information from the displaced first order passband, enables optimal reconstruction of optically sectioned images with enhanced spatial resolution. PMID- 25136488 TI - Quantitative 3D-OCT motion correction with tilt and illumination correction, robust similarity measure and regularization. AB - Variability in illumination, signal quality, tilt and the amount of motion pose challenges for post-processing based 3D-OCT motion correction algorithms. We present an advanced 3D-OCT motion correction algorithm using image registration and orthogonal raster scan patterns aimed at addressing these challenges. An intensity similarity measure using the pseudo Huber norm and a regularization scheme based on a pseudo L0.5 norm are introduced. A two-stage registration approach was developed. In the first stage, only axial motion and axial tilt are coarsely corrected. This result is then used as the starting point for a second stage full optimization. In preprocessing, a bias field estimation based approach to correct illumination differences in the input volumes is employed. Quantitative evaluation was performed using a large set of data acquired from 73 healthy and glaucomatous eyes using SD-OCT systems. OCT volumes of both the optic nerve head and the macula region acquired with three independent orthogonal volume pairs for each location were used to assess reproducibility. The advanced motion correction algorithm using the techniques presented in this paper was compared to a basic algorithm corresponding to an earlier version and to performing no motion correction. Errors in segmentation-based measures such as layer positions, retinal and nerve fiber thickness, as well as the blood vessel pattern were evaluated. The quantitative results consistently show that reproducibility is improved considerably by using the advanced algorithm, which also significantly outperforms the basic algorithm. The mean of the mean absolute retinal thickness difference over all data was 9.9 um without motion correction, 7.1 um using the basic algorithm and 5.0 um using the advanced algorithm. Similarly, the blood vessel likelihood map error is reduced to 69% of the uncorrected error for the basic and to 47% of the uncorrected error for the advanced algorithm. These results demonstrate that our advanced motion correction algorithm has the potential to improve the reliability of quantitative measurements derived from 3D-OCT data substantially. PMID- 25136489 TI - Direct observation and validation of fluorescein tear film break-up patterns by using a dual thermal-fluorescent imaging system. AB - The fluorescein tear film break-up test is a common tear film stability test for dry eye diagnosis. This test requires applying fluorescein sodium drops to a tear film to observe the tear film break-up. However, this test is limited by using the fluorescein sodium drops, which can induce reflex tearing and reduce the reliability of the diagnosis results. This paper proposes that tear film evaporation accelerates on the fluorescein tear film break-up area (FTBA), resulting in a lower temperature area (LTA) on the tear film. A dual modality system was established to capture the thermal and fluorescent image of fluorescein-stain tear films for 48 participants. Observations showed that the LTA and FTBA were highly correlated in their location (r = 0.82) and size (r = 0.91). This is first study to show that the FTBA and LTA are essentially the same region. This study demonstrated the feasibility of using the noncontact thermograph method to evaluate tear film stability without using a fluorescein sodium drop. PMID- 25136490 TI - In vivo imaging of functional microvasculature within tissue beds of oral and nasal cavities by swept-source optical coherence tomography with a forward/side viewing probe. AB - We report three-dimensional (3D) imaging of microcirculation within human cavity tissues in vivo using a high-speed swept-source optical coherence tomography (SS OCT) at 1300 nm with a modified probe interface. Volumetric structural OCT images of the inner tissues of oral and nasal cavities are acquired with a field of view of 2 mm * 2 mm. Two types of disposable and detachable probe attachments are devised and applied to the port of the imaging probe of OCT system, enabling forward and side imaging scans for selective and easy access to specific cavity tissue sites. Blood perfusion is mapped with OCT-based microangiography from 3D structural OCT images, in which a novel vessel extraction algorithm is used to decouple dynamic light scattering signals, due to moving blood cells, from the background scattering signals due to static tissue elements. Characteristic tissue anatomy and microvessel architectures of various cavity tissue regions of a healthy human volunteer are identified with the 3D OCT images and the corresponding 3D vascular perfusion maps at a level approaching capillary resolution. The initial finding suggests that the proposed method may be engineered into a promising tool for evaluating and monitoring tissue microcirculation and its alteration within a wide-range of cavity tissues in the patients with various pathological conditions. PMID- 25136491 TI - High resolution three-dimensional photoacoutic tomography with CCD-camera based ultrasound detection. AB - A photoacoustic tomograph based on optical ultrasound detection is demonstrated, which is capable of high resolution real-time projection imaging and fast three dimensional (3D) imaging. Snapshots of the pressure field outside the imaged object are taken at defined delay times after photoacoustic excitation by use of a charge coupled device (CCD) camera in combination with an optical phase contrast method. From the obtained wave patterns photoacoustic projection images are reconstructed using a back propagation Fourier domain reconstruction algorithm. Applying the inverse Radon transform to a set of projections recorded over a half rotation of the sample provides 3D photoacoustic tomography images in less than one minute with a resolution below 100 um. The sensitivity of the device was experimentally determined to be 5.1 kPa over a projection length of 1 mm. In vivo images of the vasculature of a mouse demonstrate the potential of the developed method for biomedical applications. PMID- 25136492 TI - Calcium imaging at kHz frame rates resolves millisecond timing in neuronal circuits and varicosities. AB - We have configured a widefield fast imaging system that allows imaging at 1000 frames per second (512x512 pixels). The system was extended with custom processing tools including a time correlation method to facilitate the analysis of static subcellular compartments (e.g. neuronal varicosities) with enhanced contrast, as well as a dynamic intensity processing (DIP) algorithm that aids in data size reduction and fast visualization and interpretation of timing and directionality in neuronal circuits. This system, together with our custom developed processing tools enables efficient detection of fast physiological events, such as action potential dependent calcium steps. We show, using a specific blocker of nerve communication, that with this setup it is possible to discriminate between a pre and post synaptic event in an all optical way. PMID- 25136493 TI - In vivo quantitative photoacoustic microscopy of gold nanostar kinetics in mouse organs. AB - We developed a high-resolution photoacoustic microscopy (PAM) system with a near infrared (NIR) laser to noninvasively monitor the distribution of gold nanostar (GNS) in blood vessels, liver and spleen in mice. Photoacoustic images of organs at deep depths were continuously acquired in vivo every 30 minutes after a single dose of GNS by tail vein injection. The experimental results showed that GNS accumulated significantly in both liver and spleen from blood circulation after administration, which was qualitatively validated by fluorescence imaging. Our studies demonstrate that PAM might be potentially used for noninvasive tracing the kinetics of exogenous nanoparticles in biological system. PMID- 25136494 TI - Surface modification of silica particles with gold nanoparticles as an augmentation of gold nanoparticle mediated laser perforation. AB - Gold nanoparticle mediated (GNOME) laser transfection/perforation fulfills the demands of a reliable transfection technique. It provides efficient delivery and has a negligible impact on cell viability. Furthermore, it reaches high throughput applicability. However, currently only large gold particles (> 80 nm) allow successful GNOME laser perforation, probably due to insufficient sedimentation of smaller gold nanoparticles. The objective of this study is to determine whether this aspect can be addressed by a modification of silica particles with gold nanoparticles. Throughout the analysis, we show that after the attachment of gold nanoparticles to silica particles, comparable or better efficiencies to GNOME laser perforation are reached. In combination with 1 um silica particles, we report laser perforation with gold nanoparticles with sizes down to 4 nm. Therefore, our investigations have great importance for the future research in and the fields of laser transfection combined with plasmonics. PMID- 25136495 TI - Optical design and evaluation of a 4 mm cost-effective ultra-high-definition arthroscope. AB - High definition and magnification rigid endoscope plays an important role in modern minimally invasive medical surgery and diagnosis. In this paper, we present the design and evaluation methods of a high definition rigid endoscope, specifically an arthroscope, with a large depth of field (DOF). The incident heights and exit angles of the sampled rays on the relay lens are controlled during the optimization process to ensure an effective field view (70 degrees ) and a normal ray path within the limited lens diameter of 2.7 mm. The lens is set up as a multi-configuration system with two extreme and one middle object distances to cover a large DOF. As a result, an entrance pupil of 0.3 mm is achieved for the first time, to bring the theoretical resolution to 23.1 lps/mm in the object space at a working distance of 20 mm, with the wavelength of 0.532 um. The modulation transfer function (MTF) curves approach diffraction limit, and the values are all higher than 0.3 at 160 line pairs/mm (lps/mm) in the image space. Meanwhile, stray light caused by total internal reflection on the inner wall of the rod lenses and the objective lens is eliminated. The measured resolution in the object space at a 20 mm working distance is 22.3 lps/mm, and test results show that other performance characteristics also fulfill design requirements. The relay lenses are designed with only one type of the spacer and two types of lenses to greatly reduce the fabrication and assembly cost. The design method has important research and application values for lens systems used in modern minimally invasive medical surgery and industrial non-destructive testing area. PMID- 25136496 TI - Bone tissue phantoms for optical flowmeters at large interoptode spacing generated by 3D-stereolithography. AB - A bone tissue phantom prototype allowing to test, in general, optical flowmeters at large interoptode spacings, such as laser-Doppler flowmetry or diffuse correlation spectroscopy, has been developed by 3D-stereolithography technique. It has been demonstrated that complex tissue vascular systems of any geometrical shape can be conceived. Absorption coefficient, reduced scattering coefficient and refractive index of the optical phantom have been measured to ensure that the optical parameters reasonably reproduce real human bone tissue in vivo. An experimental demonstration of a possible use of the optical phantom, utilizing a laser-Doppler flowmeter, is also presented. PMID- 25136497 TI - Measurements of extrinsic fluorescence in Intralipid and polystyrene microspheres. AB - The fluorescence of Intralipid and polystyrene microspheres with sphere diameter of 1 um at a representative lipid and microsphere concentration for simulation of mucosal tissue scattering has not been a subject of extensive experimental study. In order to elucidate the quantitative relationship between lipid and microsphere concentration and the respective fluorescent intensity, the extrinsic fluorescence spectra between 360 nm and 650 nm (step size of 5 nm) were measured at different lipid concentrations (from 0.25% to 5%) and different microsphere concentrations (0.00364, 0.0073, 0.0131 spheres per cubic micrometer) using laser excitation at 355 nm with pulse energy of 2.8 uJ. Current findings indicated that Intralipid has a broadband emission between 360 and 650 nm with a primary peak at 500 nm and a secondary peak at 450 nm while polystyrene microspheres have a single peak at 500 nm. In addition, for similar scattering properties the fluorescence of Intralipid solutions is approximately three-fold stronger than that of the microsphere solutions. Furthermore, Intralipid phantoms with lipid concentrations ~2% (simulating the bottom layer of mucosa) produce up to seven times stronger fluorescent emission than phantoms with lipid concentration ~0.25% (simulating the top layer of mucosa). The fluoresence decays of Intralipid and microsphere solutions were also recorded for estimation of fluorescence lifetime. PMID- 25136499 TI - Automatic dynamic tear meniscus measurement in optical coherence tomography. AB - An image processing algorithm is developed for quantitative assessment of tear meniscus dynamics from continuous optical coherence tomography (OCT) measurements. Clinical utility of dynamic OCT tear meniscus measurement is assessed in studies of tear meniscus parameters. The results indicate that any apparent changes in the early post-blink phase meniscus parameters are essentially related to the longitudinal movements of the eye and not to the formation of tear meniscus corresponding to tear film build-up. Dynamic acquisition of tear film meniscus is essential for providing reliable estimates of its parameters such as height, depth, and area. PMID- 25136498 TI - Fiber-based polarization-sensitive OCT of the human retina with correction of system polarization distortions. AB - In polarization-sensitive optical coherence tomography (PS-OCT) the use of single mode fibers causes unpredictable polarization distortions which can result in increased noise levels and erroneous changes in calculated polarization parameters. In the current paper this problem is addressed by a new Jones matrix analysis method that measures and corrects system polarization distortions as a function of wavenumber by spectral analysis of the sample surface polarization state and deeper located birefringent tissue structures. This method was implemented on a passive-component depth-multiplexed swept-source PS-OCT system at 1040 nm which was theoretically modeled using Jones matrix calculus. High resolution B-scan images are presented of the double-pass phase retardation, diattenuation, and relative optic axis orientation to show the benefits of the new analysis method for in vivo imaging of the human retina. The correction of system polarization distortions yielded reduced phase retardation noise, and better estimates of the diattenuation and the relative optic axis orientation in weakly birefringent tissues. The clinical potential of the system is shown by en face visualization of the phase retardation and optic axis orientation of the retinal nerve fiber layer in a healthy volunteer and a glaucoma patient with nerve fiber loss. PMID- 25136500 TI - Speckle contrast optical spectroscopy, a non-invasive, diffuse optical method for measuring microvascular blood flow in tissue. AB - We introduce a new, non-invasive, diffuse optical technique, speckle contrast optical spectroscopy (SCOS), for probing deep tissue blood flow using the statistical properties of laser speckle contrast and the photon diffusion model for a point source. The feasibility of the method is tested using liquid phantoms which demonstrate that SCOS is capable of measuring the dynamic properties of turbid media non-invasively. We further present an in vivo measurement in a human forearm muscle using SCOS in two modalities: one with the dependence of the speckle contrast on the source-detector separation and another on the exposure time. In doing so, we also introduce crucial corrections to the speckle contrast that account for the variance of the shot and sensor dark noises. PMID- 25136501 TI - Thermally enhanced signal strength and SNR improvement of photoacoustic radar module. AB - A thermally enhanced method for improving photoacoustic imaging depth and signal to-noise (SNR) ratio is presented in this paper. Experimental results showed that the maximum imaging depth increased by 20% through raising the temperature of absorbing biotissues (ex-vivo beef muscle) uniformly from 37 to 43 degrees C, and the SNR was increased by 8%. The parameters making up the Gruneisen constant were investigated experimentally and theoretically. The studies showed that the Gruneisen constant of biotissues increases with temperature, and the results were found to be consistent with the photoacousitc radar theory. PMID- 25136502 TI - Single camera imaging system for color and near-infrared fluorescence image guided surgery. AB - Near-infrared (NIR) fluorescence imaging systems have been developed for image guided surgery in recent years. However, current systems are typically bulky and work only when surgical light in the operating room (OR) is off. We propose a single camera imaging system that is capable of capturing NIR fluorescence and color images under normal surgical lighting illumination. Using a new RGB-NIR sensor and synchronized NIR excitation illumination, we have demonstrated that the system can acquire both color information and fluorescence signal with high sensitivity under normal surgical lighting illumination. The experimental results show that ICG sample with concentration of 0.13 MUM can be detected when the excitation irradiance is 3.92 mW/cm(2) at an exposure time of 10 ms. PMID- 25136503 TI - Single input state polarization sensitive swept source optical coherence tomography based on an all single mode fiber interferometer. AB - We present a newly developed single mode fiber based swept source polarization sensitive optical coherence tomography system using a single input state at 1040 nm. Two non-polarizing fiber based beam splitters are combined to form a Mach Zehnder interferometer, while two polarizing beam splitters are used to obtain a polarization sensitive detection. Both types of beam splitters solely feature conventional single mode fibers. Polarization control paddles are used to set and maintain the polarization states in the fibers of the interferometer and detection unit. By use of a special paddle alignment scheme we are able to eliminate any bulk optic wave plates and polarization maintaining fibers in the interferometer and detection paths while preserving the advantages of a single input state system that illuminates the sample with circularly polarized light. To demonstrate the capabilities of our system, we performed retinal measurements on healthy human volunteers. PMID- 25136504 TI - Frequency-modulated light scattering interferometry employed for optical properties and dynamics studies of turbid media. AB - In the present work, fiber-based frequency-modulated light scattering interferometry (FMLSI) is developed and employed for studies of optical properties and dynamics in liquid phantoms made from Intralipid((r)). The fiber based FMLSI system retrieves the optical properties by examining the intensity fluctuations through the turbid medium in a heterodyne detection scheme using a continuous-wave frequency-modulated coherent light source. A time resolution of 21 ps is obtained, and the experimental results for the diluted Intralipid phantoms show good agreement with the predicted results based on published data. The present system shows great potential for assessment of optical properties as well as dynamic studies in liquid phantoms, dairy products, and human tissues. PMID- 25136505 TI - Longitudinal vascular dynamics following cranial window and electrode implantation measured with speckle variance optical coherence angiography. AB - Speckle variance optical coherence angiography (OCA) was used to characterize the vascular tissue response from craniotomy, window implantation, and electrode insertion in mouse motor cortex. We observed initial vasodilation ~40% greater than original diameter 2-3 days post-surgery (dps). After 4 weeks, dilation subsided in large vessels (>50 um diameter) but persisted in smaller vessels (25 50 um diameter). Neovascularization began 8-12 dps and vessel migration continued throughout the study. Vasodilation and neovascularization were primarily associated with craniotomy and window implantation rather than electrode insertion. Initial evidence of capillary re-mapping in the region surrounding the implanted electrode was manifest in OCA image dissimilarity. Further investigation, including higher resolution imaging, is required to validate the finding. Spontaneous lesions also occurred in many electrode animals, though the inception point appeared random and not directly associated with electrode insertion. OCA allows high resolution, label-free in vivo visualization of neurovascular tissue, which may help determine any biological contribution to chronic electrode signal degradation. Vascular and flow-based biomarkers can aid development of novel neural prostheses. PMID- 25136506 TI - Study of freshly excised brain tissues using terahertz imaging. AB - We demonstrated that tumors in freshly excised whole brain tissue could be differentiated clearly from normal brain tissue using a reflection-type terahertz (THz) imaging system. THz binary images of brain tissues with tumors indicated that the tumor boundaries in the THz images corresponded well to those in visible images. Grey and white-matter regions were distinguishable owing to the different distribution of myelin in the brain tissue. THz images corresponded closely with magnetic resonance imaging (MRI) results. The MRI and hematoxylin and eosin stained microscopic images were investigated to account for the intensity differences in the THz images for fresh and paraffin-embedded brain tissue. Our results indicated that the THz signals corresponded to the cell density when water was removed. Thus, THz imaging could be used as a tool for label-free and real-time imaging of brain tumors, which would be helpful for physicians to determine tumor margins during brain surgery. PMID- 25136507 TI - Histology validation of mapping depth-resolved cardiac fiber orientation in fresh mouse heart using optical polarization tractography. AB - Myofiber organization in cardiac muscle plays an important role in achieving normal mechanical and electrical heart functions. An imaging tool that can reveal microstructural details of myofiber organization is valuable for both basic research and clinical applications. A high-resolution optical polarization tractography (OPT) was recently developed based on Jones matrix optical coherence tomography (JMOCT). In this study, we validated the accuracy of using OPT for measuring depth-resolved fiber orientation in fresh heart samples by comparing directly with histology images. Systematic image processing algorithms were developed to register OPT with histology images. The pixel-wise differences between the two tractographic results were analyzed in details. The results indicate that OPT can accurately image depth-resolved fiber orientation in fresh heart tissues and reveal microstructural details at the histological level. PMID- 25136508 TI - The potential of photoacoustic microscopy as a tool to characterize the in vivo degradation of surgical sutures. AB - The ex vivo and in vivo imaging, and quantitative characterization of the degradation of surgical sutures (~500 MUm diameter) up to ~1cm depth is demonstrated using a custom dark-field photo-acoustic microscope (PAM). A practical algorithm is developed to accurately measure the suture diameter during the degradation process. The results from tissue simulating phantoms and mice are compared to ex vivo measurements with an optical microscope demonstrating that PAM has a great deal of potential to characterize the degradation process of surgical sutures. The implications of this work for industrial applications are discussed. PMID- 25136509 TI - Interspecific hybridization as a genomic stressor inducing mobilization of transposable elements in Drosophila. AB - Transposable elements (TEs) are DNA sequences able to be mobilized in host genomes. They are currently recognized as the major mutation inducers because of their insertion in the target, their effect on neighboring regions, or their ectopic recombination. A large number of factors including chemical and physical factors as well as intraspecific crosses have traditionally been identified as inducers of transposition. Besides environmental factors, interspecific crosses have also been proposed as promoters of transposition of particular TEs in plants and different animals. Our previous published work includes a genome-wide survey with the set of genomic TEs and shows that interspecific hybridization between the species Drosophila buzzatii and Drosophila koepferae induces genomic instability by transposition bursts. A high percentage of this instability corresponds to TEs belonging to classes I and II. The detailed study of three TEs (Osvaldo, Helena, and Galileo), representative of the different TE families, shows an increase of transposition in hybrids compared with parental species, that varies depending on the element. This study suggests ample variation in TE regulation mechanisms and the question is why this variation occurs. Interspecific hybridization is a genomic stressor that disrupts the stability of TEs probably contributing to a relaxation of the mechanisms controlling TEs in the Drosophila genome. In this commentary paper we will discuss these results and the molecular mechanisms that could explain these increases of transposition rates observed in interspecific Drosophila hybrids. PMID- 25136510 TI - Production of therapeutic proteins in the chloroplast of Chlamydomonas reinhardtii. AB - Chloroplast transformation in the photosynthetic alga Chlamydomonas reinhardtii has been used to explore the potential to use it as an inexpensive and easily scalable system for the production of therapeutic recombinant proteins. Diverse proteins, such as bacterial and viral antigens, antibodies and, immunotoxins have been successfully expressed in the chloroplast using endogenous and chimeric promoter sequences. In some cases, proteins have accumulated to high level, demonstrating that this technology could compete with current production platforms. This review focuses on the works that have engineered the chloroplast of C. reinhardtii with the aim of producing recombinant proteins intended for therapeutical use in humans or animals. PMID- 25136511 TI - Highly conserved salt bridge stabilizes a proteinase K subfamily enzyme, Aqualysin I, from Thermus aquaticus YT-1. AB - The proteinase K subfamily enzymes, thermophilic Aqualysin I (AQN) from Thermus aquaticus YT-1 and psychrophilic serine protease (VPR) from Vibrio sp. PA-44, have six and seven salt bridges, respectively. To understand the possible significance of salt bridges in the thermal stability of AQN, we prepared mutant proteins in which amino acid residues participating in salt bridges common to proteinase K subfamily members and intrinsic to AQN were replaced to disrupt the bridges one at a time. Disruption of a salt bridge common to proteinase K subfamily enzymes in the D183N mutant resulted in a significant reduction in thermal stability, and a massive change in the content of the secondary structure was observed, even at 70 degrees C, in the circular dichroism (CD) analysis. These results indicate that the common salt bridge Asp183-Arg12 is important in maintaining the conformation of proteinase K subfamily enzymes and suggest the importance of proximity between the regions around Asp183 and the N-terminal region around Arg12. Of the three mutants that lack an AQN intrinsic salt bridge, D212N was more prone to unfolding at 80 degrees C than the wild-type enzyme. Similarly, D17N and E237Q were less thermostable than the wild-type enzyme, although this may be partially due to increased autolysis. The AQN intrinsic salt bridges appear to confer additional thermal stability to this enzyme. These findings will further our understanding of the factors involved in stabilizing protein structure. PMID- 25136512 TI - Imaging of alpha7 nicotinic acetylcholine receptors in brain and cerebral vasculature of juvenile pigs with [(18)F]NS14490. AB - BACKGROUND: The alpha7 nicotinic acetylcholine receptor (nAChR) is an important molecular target in neuropsychiatry and oncology. Development of applicable highly specific radiotracers has been challenging due to comparably low protein expression. To identify novel ligands as candidates for positron emission tomography (PET), a library of diazabicyclononane compounds was screened regarding affinity and specificity towards alpha7 nAChRs. From these, [(18)F]NS14490 has been shown to yield reliable results in organ distribution studies; however, the radiosynthesis of [(18)F]NS14490 required optimization and automation to obtain the radiotracer in quantities allowing dynamic PET studies in piglets. METHODS: Automated radiosynthesis of [(18)F]NS14490 has been performed by [(18)F]fluorination with the tosylate precursor in the TRACERlabTM FX F-N synthesis module (Waukesha, WI, USA). After optimization, the radiochemical yield of [(18)F]NS14490 was consistently approximately 35%, and the total synthesis time was about 90 min. The radiotracer was prepared with >92% radiochemical purity, and the specific activity at the end of the synthesis was 226 +/- 68 GBq MUmol(-1). PET measurements were performed in young pigs to investigate the metabolic stability and cerebral binding of [(18)F]NS14490 without and with administration of the alpha7 nAChR partial agonist NS6740 in baseline and blocking conditions. RESULTS: The total distribution volume relative to the metabolite-corrected arterial input was 3.5 to 4.0 mL g(-1) throughout the telencephalon and was reduced to 2.6 mL g(-1) in animals treated with NS6740. Assuming complete blockade, this displacement indicated a binding potential (BPND) of approximately 0.5 in the brain of living pigs. In addition, evidence for specific binding in major brain arteries has been obtained. CONCLUSION: [(18)F]NS14490 is not only comparable to other preclinically investigated PET radiotracers for imaging of alpha7 nAChR in brain but also could be a potential PET radiotracer for imaging of alpha7 nAChR in vulnerable plaques of diseased vessels. PMID- 25136514 TI - 4D PET/CT as a Strategy to Reduce Respiratory Motion Artifacts in FDG-PET/CT. AB - The improved accuracy in tumor identification with FDG-PET has led to its increased utilization in target volume delineation for radiotherapy treatment planning in the treatment of lung cancer. However, PET/CT has constantly been influenced by respiratory motion-related image degradation, which is especially prominent for small lung tumors in the peri-diaphragmatic regions of the thorax. Here, we describe the current findings on respiratory motion-related image degradation in PET/CT, which may bring uncertainties to target volume delineation for image guided radiotherapy (IGRT) for lung cancer. Furthermore, we describe the evidence suggesting 4D PET/CT to be one strategy to minimize the impact of respiratory motion-related image degradation on tumor target delineation for thoracic IGRT. This, in our opinion, warrants further investigation in future IGRT-based lung cancer trials. PMID- 25136513 TI - Genetically engineered mouse models of pituitary tumors. AB - Animal models constitute valuable tools for investigating the pathogenesis of cancer as well as for preclinical testing of novel therapeutics approaches. However, the pathogenic mechanisms of pituitary-tumor formation remain poorly understood, particularly in sporadic adenomas, thus, making it a challenge to model pituitary tumors in mice. Nevertheless, genetically engineered mouse models (GEMMs) of pituitary tumors have provided important insight into pituitary tumor biology. In this paper, we review various GEMMs of pituitary tumors, highlighting their contributions and limitations, and discuss opportunities for research in the field. PMID- 25136515 TI - Drug-diagnostics co-development in oncology. PMID- 25136517 TI - Head and neck cancers: Safely preserving the talk. PMID- 25136518 TI - Pathology of radiation toxicity and its implication on quality of life. PMID- 25136516 TI - Induction of endoplasmic reticulum stress and unfolded protein response constitutes a pathogenic strategy of group A streptococcus. AB - The connection between bacterial pathogens and unfolded protein response (UPR) is poorly explored. In this review we highlight the evidence showing that group A streptococcus (GAS) induces endoplasmic reticulum (ER) stress and UPR through which it captures the amino acid asparagine (ASN) from the host. GAS acts extracellularly and during adherence to host cells it delivers the hemolysin toxins; streptolysin O (SLO) and streptolysin S (SLS). By poorly understood pathways, these toxins trigger UPR leading to the induction of the transcriptional regulator ATF4 and consequently to the upregulation of asparagine synthetase (ASNS) transcription leading to production and release of ASN. GAS senses ASN and alters gene expression profile accordingly, and increases the rate of multiplication. We suggest that induction of UPR by GAS and by other bacterial pathogens represent means through which bacterial pathogens gain nutrients from the host, obviating the need to become internalized or inflict irreversible cell damage. PMID- 25136520 TI - Genetically altered fields in head and neck cancer and second field tumor. AB - The concept of field cancerization has been ever changing since its first description by Slaughter et al in 1953. Field cancerization explains the mechanisms by which second primary tumors (SPTs) develop. SPTs are the tumors, which develop in the oral cavity in succession to the primary malignant tumors, which might vary in duration ranging from few months to years. Conceivably, a population of daughter cells with early genetic changes (without histopathology) remains in the organ, demonstrating the concept of field cancerization. This review explains the concept of field cancerization and various field theories along with molecular basis of field formation. PMID- 25136521 TI - Association of cytochrome P450 2C9 polymorphism with locally advanced head and neck squamous cell carcinoma and response to concurrent cisplatin-based radical chemoradiation. AB - AIMS: The aim of the present study is to investigate the association between polymorphism of cytochrome P450 2C9 (CYP2C9) enzyme with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving cisplatin-based radical chemoradiation (CT-RT). MATERIALS AND METHODS: Four hundred and sixty patients suffering from locally advanced HNSCC and an equal number of healthy controls were genotyped for CYP2C9*2 and CYP2C9*013, leading to poor metabolizers (PMs) by polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). Each case was assessed thoroughly for treatment response as per the World Health Organization (WHO) criteria. RESULTS AND ANALYSIS: The frequency of heterozygous genotypes of both CYP2C9*2 (27.8%) and CYP2C9*3 (25%) were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several folds increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9*2 or CYP2C9*013. Further, majority of the cases assessed for response (n = 436) carrying variant alleles of CYP2C9*2 (69.6%) or CYP2C9*3 (65.2%) were found to respond poorly to cisplatin-based radical CT-RT. CONCLUSION: The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment protocol. PMID- 25136519 TI - Organ preservation strategies: Review of literature and their applicability in developing nations. AB - There has been a change in practice in locally advanced laryngopharyngeal cancers toward non-surgical treatment modalities. Although, there have been landmark trials pertinent to organ preservation, their applicability in developing nations is a topic of much debate. The organ preservation concept was based on the findings of pivotal trials by the Veterans Affairs, European Organization for Research and Treatment of Cancer group and Radiation Therapy Oncology Group. Subsequently numerous studies have been designed to evaluate intensification of treatment as well as study toxicity and tolerability. This review critically analyses current evidence for larynx preservation, experience from various centers on organ preservation strategies as well as applicability of these protocols to developing nations. PMID- 25136522 TI - Post-radiation changes in oral tissues - An analysis of cancer irradiation cases. AB - INTRODUCTION: Radiation, commonly employed as neoadjuvant, primary, and adjuvant therapy for head and neck cancer causes numerous epithelial and stromal changes, prominent among which is fibrosis with its early and late consequences. Very little is known about the true nature of the fibrosed tissue and the type of fibers accumulated. Radiotherapy affects the supporting tumor stroma often resulting in a worsening grade of tumor post-radiation. AIM: To study epithelial, neoplastic, stromal, and glandular changes in oral cavity induced by radiation therapy for oral squamous cell carcinoma (OSCC) using special stains. MATERIALS AND METHODS: The study included 27 samples of recurrent OSCC following completion of radiotherapy (recurrence within an average span of 11 months), and 26 non irradiated cases of OSCC. Patients with a history of combined radiotherapy and chemotherapy were not included in the study. The epithelial changes assessed included epithelial atrophy, apoptosis, necrosis, dysplasia, and neoplasia. The connective tissue was evaluated for amount of fibrosis, quality of fibers (using picrosirius red staining), fibrinous exudate, necrosis, pattern of invasion, vessel wall thickening, and salivary gland changes. The aforementioned changes were assessed using light and polarizing microscopy and tabulated. STATISTICAL ANALYSIS: Epithelial and connective tissue parameters were compared between the irradiated and non-irradiated cases using chi square and t-tests. RESULTS: Epithelial and connective tissue parameters were found to be increased in irradiated patients. Pattern of invasion by tumor cells varied from strands and cords between the two groups studied. The effect of radiation was seen to reflect on the maturity of fibers and the regularity of their distribution. PMID- 25136523 TI - Survival outcome of malignant minor salivary tumors in Pakistani population. AB - OBJECTIVE: Malignant tumors of minor salivary glands (MSG) are rare. Survival outcome in Pakistani population with malignant MSG tumors remains to be defined. The objective of this study was to report the clinical presentation, treatment modalities, and survival outcome of radically treated malignant tumors of MSG in Pakistani population. MATERIALS AND METHODS: Between April 2003 and March 2011, 45 patients with malignant tumors of MSG were treated at Shaukat Khanum Cancer Hospital and included in the study. Patient characteristics and treatment modalities were assessed and local, regional, and distant failures determined. Relapse-free (RFS) and overall survival (OS) was calculated using Kaplan-Meier curves, and log-rank test was used to determine significance. RESULTS: Median age was 40 (17-83) years. Male to female ratio was 1.25:1. Most common site was hard palate in 31 (69%) patients. Adenoid cystic carcinoma (51%) was the most common histological diagnosis. Nine patients (20%) underwent surgery as the only treatment modality, six patients received (13%) radiotherapy alone, and 30 patients (67%) had surgery followed by adjuvant radiotherapy. Eight patients developed recurrence (four local, two regional, one locoregional, and one distant). The 5-year actuarial overall OS and RFS was 77 and 66%, respectively. Age, T-stage, and treatment modality were significant for RFS, whereas T-stage and treatment modality were significant factors for OS. CONCLUSION: Surgery as single modality or combined with radiation therapy resulted in acceptable survival in Pakistani population with malignant minor salivary tumors. PMID- 25136524 TI - Palliative low dose fortnightly methotrexate in oral cancers: Experience at a rural cancer centre from India. AB - CONTEXT: Palliative fortnightly chemotherapy in oral cancers. AIMS: We present our experience with a regimen employing fortnightly (once in 2 weeks) injectable methotrexate (MTX) (40 mg/m(2) ) in a predominantly elderly cohort of patients with carcinoma of oral cavity and oropharynx. SETTINGS AND DESIGN: Retrospective chart review conducted at a rural cancer center in India. MATERIALS AND METHODS: All patients with oral cavity and oropharyngeal cancers started on treatment with fortnightly injectable MTX (40 mg/m(2) ) between 01/01/2011 and 31/12/2011. STATISTICAL ANALYSIS USED: The factors analyzed included the duration of disease control, pain control, overall survival and progression free survival which were evaluated using the Kaplan Meier method. RESULTS: A total of 60 patients with a median age of 66.5 years were analyzed. Majority of the patients had poor nutritional status, performance status or co-morbidities. MTX was given for recurrent disease in 19 patients and after initial palliative radiotherapy in 41 patients. The median number of cycles delivered was nine. Grade 3/4 toxicities were seen in 2 patients only. Disease control rate at the end of treatment was seen in 33 (55%) patients. Median overall survival was 34 weeks (interquartile range: 17-50 weeks). CONCLUSIONS: The fortnightly regimen of MTX was well tolerated and showed a good clinical activity in this elderly cohort of patients with advanced oral cavity and oropharyngeal cancers. PMID- 25136525 TI - Relationship of angiogenic and apoptotic activities in soft-tissue sarcoma. AB - INTRODUCTION: Angiogenesis and apoptosis play an essential role in tumor development and progression. Previous studies on apoptosis and angiogenesis of soft-tissue sarcoma (STS) were done separately. This is the first study of the relationship between apoptotic and angiogenic activity. Correlation of expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax) in the tumor cells (TCs) with their expression in endothelial cell (EC) of the tumor blood vessels in STS were also carried out. MATERIALS AND METHODS: 101 cases of STS; consisting liposarcoma, malignant fibrous histiocytoma, synovial sarcoma, fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma and malignant peripheral nerve sheath tumor; were collected and immunohistochemical reaction of vascular endothelial growth factor (VEGF), Bcl-2 and Bax were examined. RESULTS: Higher Bax expression in TCs (54.5%) was seen compared to Bcl-2 expression (44.6%). There was a significant association between Bcl-2 and Bax in TCs with ECs. Significant association was also seen between histological types of STS with Bcl 2 expression; however not with Bax expression. There was an association between VEGF and Bax with high VEGF expression and weak Bax expression. However, VEGF expression was not associated with Bcl-2 expression and histological types. CONCLUSION: This study supports the role of ECs of tumor blood vessels and apoptosis of TCs in tumor management. Increased angiogenesis may inhibit apoptosis of TCs and lead to tumor growth. Therefore, inhibition of ECs survival or activation of ECs death is promising prospect for tumor therapy. Immunohistochemical antibodies in this study might be potential useful marker for the prognosis of STS. PMID- 25136526 TI - Biweekly cetuximab and first-line chemotherapy in chinese patients with k-ras wild-type colorectal cancers. AB - BACKGROUND: The efficacy and safety of using combination chemotherapy with cetuximab as first-line treatment in patients with K-ras wild-type colorectal cancers has been well established. In general, weekly cetuximab was given with biweekly chemotherapy FOLFOX-4 or FOLFIRI, synchronizing them would be appealed to both patients and health care professionals. MATERIALS AND METHODS: This Phase II, prospective study investigated the efficacy and safety of using biweekly cetuximab 500 mg/m(2) with chemotherapy FOLFOX-4 or FOLFIRI as first-line treatment for Chinese patients with K-ras wild-type metastatic colorectal cancer. The study endpoints included overall objective response (OR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Total 15 Chinese patients (male: 10 [67%]; median age: 60 [range 41-80]) were enrolled. Patients received median 12 cycles (range 2-12) of chemotherapy + cetuximab (FOLFOX-4 + cetuximab: 9 [60%]; FOLFIRI + cetuximab: 6 [40%]). Six patients (40%) with non progressive disease after 12 cycles of chemotherapy + cetuximab carried on maintenance cetuximab. Median duration of follow-up (FU) was 23.7 months. The OR was 40% (complete response: 0%; partial response: 40%) for a disease control rate of 87%. Median PFS and OS were 7.8 months and 17.9 months respectively. For maintenance cetuximab phase, median PFS since the start of maintenance cetuximab was 6.8 months and median OS was 17.0 months. The only grade 3-4 toxicities were neutropenia (26.7%) in chemotherapy phase and acneiform rashes (16.7%) in maintenance phase. CONCLUSIONS: Biweekly cetuximab with combination chemotherapy was effective and safe as weekly dose. Further studies are warranted for the role of maintenance cetuximab. PMID- 25136527 TI - A retrospective study of clinico-pathological spectrum of carcinoma breast in a West Delhi, India. AB - BACKGROUND: Data on the demographic profile of breast cancer patients from Delhi is scarce and whatever is available is from higher referral center. Our hospital caters to patients from an urban population of the lower socioeconomic strata and is a representation of cases at a tertiary care hospital in west Delhi. In Delhi, breast cancer (26.8%) is commonest cancer among the female followed by cervix (12.5%), gallbladder (7.2%), ovary (7.1%), and uterus (3.3%). AIMS AND OBJECTIVES: A retrospective audit of breast cancer patients presenting at a tertiary referral center from 2004 to 2011. MATERIALS AND METHODS: A total of 328 cases diagnosed as carcinoma breast on histopathology from year 2004 to 2011 were retrieved and studied retrospectively with regards to demographic profile and their histological features with estrogen receptor (ER), progesterone receptor (PR), and Her2neu status. RESULTS: The median age of presentation was 49 years of age. Infiltrating ductal carcinoma (IDC, not otherwise specified (NOS)) was the commonest histopathological variant (81.40%) followed by medullary carcinoma (10.36%) and mucinous carcinoma (2.74%). Triple negative were found to be the commonest group comprising 39.4% of all the cases followed by ER and PR both positive. Pathological tumor, node, and metastasis (TNM) staging showed most common group was T2N0M0 (19.5%) followed by T2N1M0 (17.1%) and T2N2M0 (14%). CONCLUSION: The incidence of breast cancer in the India and include a higher incidence of ER, PR, and Her2neu negative disease in west Delhi. PMID- 25136528 TI - Tolvaptan. AB - Hyponatremia is a common and often under-recogonised clinical problem in oncologic practice. The recogonition of the cause of hyponatremia and initiation of appropriate and timely intervention can prevent morbidity and improve treatment tolerance. This drug review aims at discussing the currently approved oral vaptanagent Tolvaptan. Vaptans including Tolvaptan act as "aquaretic" agents cousing excretion of water while retaining the sodium. Administration of this agent for prescribed periods result in improvement of serum sodium levels. The drug can be used in many clinical situations resulting in hyponatremia including congestive heart failure, cirrhosis and syndrome of inappropriate ADH secretion (SIADH) including SIADH related to malignancies. PMID- 25136529 TI - Radiation stents: Minimizing radiation-induced complications. PMID- 25136530 TI - Waste landfill site fire crisis in Thailand; sulfur dioxide pollution and estimation of cancer risk. PMID- 25136531 TI - Diffuse large B-cell lymphoma in patients with chronic lymphocytic leukemia: A single center experience. PMID- 25136532 TI - Giant anterior ameloblastoma managed by wide excision mandibulectomy with intraoral primary mucosal closure and skin defect coverage by deltopectoral flap. PMID- 25136533 TI - Shewanella algae: First case report of the fast emerging marine pathogen from squamous cell carcinoma patient in India. PMID- 25136534 TI - Expected efficacy of HPV vaccine in prevention of cervix cancer in Thailand. PMID- 25136535 TI - Dietary factors and the risk of thyroid cancer: a review. AB - In the past few decades, the incidence of thyroid cancer has rapidly increased worldwide. Thyroid cancer incidence is relatively high in regions where the population's daily iodine intake is insufficient. While low dietary iodine has been considered as a risk factor for thyroid cancer development, previous studies found controversial results across different food types. Among different ethnic groups, dietary factors are influenced by various dietary patterns, eating habits, life-styles, nutrition, and other environmental factors. This review reports the association between dietary factors and thyroid cancer risk among ethnic groups living in different geologic regions. Iodine-rich food such as fish and shellfish may provide a protective role in populations with insufficient daily iodine intake. The consumption of goitrogenic food, such as cruciferous vegetables, showed a positive association with risk. While considered to be a risk factor for other cancers, alcohol intake showed a protective role against thyroid cancer. High consumption of meat such as chicken, pork, and poultry showed a positive association with the risk, but dairy products showed no significant association. Regular use of multivitamins and dietary nitrate and nitrite also showed a positive association with thyroid cancer risk. However, the study results are inconsistent and investigations into the mechanism for how dietary factors change thyroid hormone levels and influence thyroid function are required. PMID- 25136536 TI - Effects of Korean White Ginseng (Panax Ginseng C.A. Meyer) on Vascular and Glycemic Health in Type 2 Diabetes: Results of a Randomized, Double Blind, Placebo-controlled, Multiple-crossover, Acute Dose Escalation Trial. AB - Korean red ginseng (steam treated Panax ginseng C.A. Meyer), among most prized traditional herbal remedies, has been clinically shown to improve cardiovascular disease (CVD) risk factors. Whether this holds true for the dried non-steamed variety, known as Korean white ginseng (KWG) is unclear. This study therefore, investigated the efficacy and safety of escalating doses of KWG on vascular and glycemic parameters in type 2 diabetes (T2DM). Using an acute, randomized, placebo-controlled, double-blind, crossover design, 25 participants with well controlled T2DM (12-males: 13-females, age: 63 +/- 9 years, A1c: 6.9 +/- 0.7%, BMI: 29.3 +/- 4.3 kg/m(2)) underwent five visits during which they received 1 g, 3 g, or 6 g KWG or 3 g wheat-bran control (twice) together with 50 g-glucose load. For the duration of 240 minutes, augmentation index (AI), and central blood pressure were measured at baseline and at 60 min-intervals, and ambulatory blood pressure was assessed at baseline and at 10 min-intervals. Additionally, capillary blood was collected at time zero and at 15, 30, 45, 60, 90, 120, and 180 minutes post-treatment. A symptoms questionnaire was used to assess safety and adverse events. Two-way ANOVA demonstrated a significant time-treatment interaction effect on AI (p = 0.01) with one-way ANOVA showing significant reductions in AI with 3 g KWG relative to control (p = 0.04). Compared to control, acute administration of KWG appeared to be safe, but did not affect any other postprandial, vascular or glycemic parameters. KWG might have a beneficial effect on AI, a cumulative indicator of arterial health. However, these results are preliminary and highlight the need for long-term investigation with a focus on its accountable components. CLINICAL TRIAL REGISTRATION: NCT01699074. PMID- 25136537 TI - Immunomodulatory effects of kimchi in chinese healthy college students: a randomized controlled trial. AB - This study examined the potential immunomodulatory effects of Kimchi, a traditional fermented Korean vegetable, in healthy Chinese college students. The four-week clinical-trial (randomized, open-label, prospective, controlled) was followed by a one week wash-out period. Healthy Chinese college students (over 20 years of age with a body mass index of 18.5-23.0 kg/m(2)) volunteered for this study. Forty-three students were randomly classified into two groups, Kimchi (n = 21, supplemented with 100 g of Kimchi per day) or non-Kimchi (n = 22, supplemented with 100 g of radish per day, control) groups. During the four-week intervention period, students were asked to maintain their usual diet and activity, and instructed not to take any medications, functional food products, or dietary supplements. Anthropometrics, nutritional intake, and blood immune parameters (lymphocyte subsets, cytokines, and immunoglobulins) were measured before and after the four weeks of intervention. Thirty-nine students (19 in the Kimchi group, 20 in the non-Kimchi group) finished the study. After the intervention, no significant changes were observed in lymphocyte subsets (T-cell, B-cell, NK cell), pro-inflammatory cytokines (IL-6, TNF-alpha), anti-inflammatory cytokines (IL-4 and IL-10), and immunoglobulins (Ig A, G, and M) between groups in either the Kimchi or non-Kimchi. These results suggest that the short-term consumption of Kimchi has no immunomodulatory effects in healthy Chinese college students. PMID- 25136538 TI - Effects of diet modification on meal quality and quality of life in korean diabetic patients: data from Korea national health and nutrition examination survey (2007-2011). AB - It is generally accepted that diet modification provides beneficial effects on the management of diabetes. In the present study, we evaluated the effects of diet modification on nutrient intake and quality of life in a large sample of diabetic patients. This study was conducted using data from the Korea National Health and Nutrition Examination Survey IV and V (2007-2010). A total of 2,484 of diabetic patients were included in the analysis. Then, we compared the overall quality of dietary intake between diabetic patients with diet modification and those without dietary modification. The result showed that subjects on diabetic diet (DDG) showed lower levels of total cholesterol, triglyceride, and AST before and after the adjustment for covariates (all p < 0.05). The results of nutrient assessment showed that DDG had lower intakes of total energy, fat, and carbohydrate (all p < 0.05), but higher intakes of energy from protein, vitamin B1, vitamin B2, niacin and vitamin C than NDG. (all p < 0.05). In addition, nutritional adequacy ratio of calcium and vitamin B2 were significantly higher in DDG than those in normal diet group (NDG) (p < 0.05). However, we observed no significant differences in quality of life between two groups. In conclusion, diet modification in diabetic patients seemed to be effective to improve blood lipid profile and the adequacy of nutrient intake without sacrificing the quality of life. PMID- 25136539 TI - Development and Evaluation of a Web-based Computer-Assisted Personal Interview System (CAPIS) for Open-ended Dietary Assessments among Koreans. AB - The accuracy of dietary assessments has emerged as a major concern in nutritional epidemiology and new dietary assessment tools using computer technology to increase accuracy have been developed in many countries. The purpose of this study was to develop a web-based computer-assisted personal interview system (CAPIS) for conducting dietary assessment and to evaluate its practical utilization among Koreans. The client software was developed using Microsoft's ClickOnce technology, which allows communication with a database system via an http server to add or retrieve data. The system consists of a tracking system for the subject and researcher, a data-input system during the interview, a calculation system for estimating food and nutrient intake, a data-output system for presenting the results, and an evaluation system for assessing the adequacy of nutrient and food intake. Databases of the nutrient composition of common food (n = 3,642), recipes for common dishes (n = 1,886), and photos of serving sizes for food and dishes (n = 4,152) were constructed, and logical processes for data collection, calculation, and output were developed. The functionality, on-site applicability, and efficiency of CAPIS were evaluated in a convenience sample of 181 participants (61 males, 120 females; aged 24 to 85) by comparing with manual 24 hour recall method with paper questionnaire. The CAPIS was functioned adequately in the field survey in terms of completeness of function, security, and compliance of researcher and subjects. Regarding on-site applicability, 23.2%, 32.6%, 35.4%, and 43.7% of subjects reported that CAPIS was easier to recall their diet, to estimate the amount consumed, to communicate with the interviewer, and to concentrate on the interview than the manual method with paper questionnaire, respectively. Although CAPIS required more interview time (9 min 42 sec) compared to the manual method (7 min 30 sec), it saved time and cost for data coding and entry (15 min 35 sec) and gave high satisfaction from the prompt feedback after interview to the subjects, which increase efficiency to apply on the field survey. Our results suggest that the newly developed CAPIS is suitable for conducting personal interviews for dietary assessment in Korean population. PMID- 25136540 TI - Evaluation of fruit intake and its relation to body mass index of adolescents. AB - Diets high in fruits and vegetables are recommended to maintain health. However, accurate fruit intake evaluation is hard and high sugar content in most of the fruits suggest possible negative relationships with health indices. The purpose of the present study was to evaluate the fruit intake status of adolescents and to examine the relationship between fruit intake and body mass index (BMI). For this, 400 middle and high school students were surveyed for their fruit eating attitude, preference, and intake level for fruit along with the evaluation of their relationship with anthropometric measures. As for fruit preference, the most frequent answer was 'like very much' (60.0%) and the preference of fruit was significantly higher in females than in males (p < 0.01). The highest answer to the reason to like fruits was 'delicious' (67.0%). The highest proportion of subjects replied that the amount of fruit intake was similar in both school meals and at home (39.3%) and unlikable feeling of fruits was 'sour' (47.0%). The favorite fruit was the apple followed by oriental melon, grape, Korean cherry, cherry, tangerine/orange, hallabong, plum, mango, persimmon, peach, pear/kiwi, apricot, Japanese apricot, and fig in order. As for the number of serving sizes per person were 2.9 times/day for male students and 3.0 times/day for female students showing no significant difference. The frequency of eating fruits in the evening showed a significant positive correlation with body weight (p < 0.05) and BMI (p < 0.01), respectively. In summary of these study findings, it was found that the fruit preference of adolescents was relatively high and their fruit intake level satisfied the recommended number of intake. The number of evening fruit intake had a significantly positive correlation with body weight and BMI. Further studies are required to examine the relationship between fruit intake and health indicators. PMID- 25136541 TI - Coffee enema for preparation for small bowel video capsule endoscopy: a pilot study. AB - Coffee enemas are believed to cause dilatation of bile ducts and excretion of bile through the colon wall. Proponents of coffee enemas claim that the cafestol palmitate in coffee enhances the activity of glutathione S-transferase, an enzyme that stimulates bile excretion. During video capsule endoscopy (VCE), excreted bile is one of the causes of poor preparation of the small bowel. This study aimed to evaluate the feasibility and effect of coffee enema for preparation of the small bowel during VCE. In this pilot study, 17 of 34 patients were assigned to the coffee enema plus polyethylene glycol (PEG) 2 L ingestion group, whereas the 17 remaining control patients received 2 L of PEG only. The quality of bowel preparation was evaluated in the two patient groups. Bowel preparations in the proximal segments of small bowel were not differ between two groups. In the mid and distal segments of the small intestine, bowel preparations tend to be better in patients who received coffee enemas plus PEG than in patients who received PEG only. The coffee enema group did not experience any complications or side effects. Coffee enemas may be a feasible option, and there were no clinically significant adverse events related to coffee enemas. More prospective randomized studies are warranted to improve small bowel preparation for VCE. PMID- 25136542 TI - Compromised Diet Quality is Associated with Decreased Renal Function in Children with Chronic Kidney Disease. AB - Nutritional status of children with chronic kidney disease (CKD) is important since it affects growth and development. This study was to investigate overall diet quality measured by nutrient intake adequacy, nutrient density, and several dietary habits in children with CKD and its relationship with clinical parameters according to glomerular filtration rate (GFR). Assessment of nutritional status and diet quality was conducted in nineteen children with CKD. Average Z-scores of height, weight and body mass index (BMI) in the participants were less than standard growth rate. Nutritional status, such as Z-scores of height (p < 0.05) and serum total protein (p < 0.05), were significantly lower in the children with GFR < 75 mL/min/1.73 m(2) compared to those with GFR >= 75 mL/min/1.73 m(2). Nutrition adequacy ratio of energy, thiamin, riboflavin, vitamin B6, folate, iron, and zinc and overall diet quality were significantly poorer in the children with GFR < 75 mL/min/1.73 m(2). Poorer appetite and avoidance of food were observed in the children with higher blood urea nitrogen (BUN). Intakes of iron, zinc, thiamin, niacin, and vitamin B6 were positively correlated with GFR. Intakes of calcium, potassium and folate were positively correlated with BUN, while protein intakes were negatively correlated. Overall nutrient intakes were inadequate and diet quality was decreased as kidney function was decreased. Dietary habit and appetite were also related with kidney function in this study subjects. Systemic efforts of nutritional intervention are imperative to prevent deteriorating growth and development and improve the nutritional status in children with CKD. PMID- 25136543 TI - Medical Nutrition Therapy based on Nutrition Intervention for a Patient with Chronic Obstructive Pulmonary Disease. AB - Chronic obstructive pulmonary disease (COPD) is a major cause of disability, and according to statistics from the World Health Organization, COPD is the fourth leading cause of death overall in the face of decades, and expected to be increased. In 2005, the reported prevalence of COPD in Korea was 17.2% of adults over the age of 45. Malnutrition is a common problem in papatients with COPD. And several nutritional intervention studies showed a significant improvement in physical and functional outcomes. According to the results of previous studies, the nutritional support is important. This is a case report of a patient with COPD who was introduced to a proper diet through nutrition education based on the medical nutrition therapy protocol for COPD. PMID- 25136544 TI - Changes in fat intake, body fat composition and intra-abdominal fat after bariatric surgery. AB - Bariatric surgery is considered to be the effective treatment alternative conducted over the lifetime for reducing weight in patients with clinically morbid obesity. For many patients, the benefits of weight loss, including decreases in blood glucose, lipids, and blood pressure as well as increase in mobility, will outweigh the risks of surgical complications. But patients undergoing bariatric surgery have the least risk for long-term diet-related complications as reported in several studies. Thus, with an increasing number of severely obese patients undergoing bariatric surgery, the multidisciplinary healthcare system will need to be managed continuously. Many nutrition support specialists will need to become familiar with the metabolic consequences for the frequent monitoring of nutrition status of the patients. South Korea has a very short history with bariatric surgery, and relatively few studies have been conducted on bariatric surgery. Therefore, the objective of this report was to compare the nutrient intake, weight loss, body fat composition, and visceral fat before and after the bariatric surgery. PMID- 25136545 TI - Reducing auditory hypersensitivities in autistic spectrum disorder: preliminary findings evaluating the listening project protocol. AB - Auditory hypersensitivities are a common feature of autism spectrum disorder (ASD). In the present study, the effectiveness of a novel intervention, the listening project protocol (LPP), was evaluated in two trials conducted with children diagnosed with ASD. LPP was developed to reduce auditory hypersensitivities. LPP is based on a theoretical "neural exercise" model that uses computer altered acoustic stimulation to recruit the neural regulation of middle ear muscles. Features of the intervention stimuli were informed by basic research in speech and hearing sciences that has identified the specific acoustic frequencies necessary to understand speech, which must pass through middle ear structures before being processed by other components of the auditory system. LPP was hypothesized to reduce auditory hypersensitivities by increasing the neural tone to the middle ear muscles to functionally dampen competing sounds in frequencies lower than human speech. The trials demonstrated that LPP, when contrasted to control conditions, selectively reduced auditory hypersensitivities. These findings are consistent with the polyvagal theory, which emphasizes the role of the middle ear muscles in social communication. PMID- 25136546 TI - Focus on apoptosis to decipher how alcohol and many other drugs disrupt brain development. PMID- 25136547 TI - Developing a Dissemination Model to Improve Intervention Reach among West Virginia Youth Smokers. AB - The not-on-tobacco program is an evidence-based teen smoking cessation program adopted by the American Lung Association (ALA). Although widely disseminated nationally via ALA Master Trainers, in recent years, adoption and implementation of the N-O-T program in West Virginia (WV) has slowed. WV, unfortunately, has one of the highest smoking rates in the US. Although it is a goal of public health science, dissemination of evidence-based interventions is woefully understudied. The present manuscript reviews a theoretical model of dissemination of the not-on tobacco program in WV. Based on social marketing, diffusion of innovations, and social cognitive theories, the nine-phase model incorporates elements of infrastructure development, accountability, training, delivery, incentives, and communication. The model components as well as preliminary lessons learned from initial implementation are discussed. PMID- 25136548 TI - Biosecurity Policy in the US: A Critical Assessment. PMID- 25136549 TI - Polycyclic aromatic compounds as anticancer agents: synthesis and biological evaluation of methoxy dibenzofluorene derivatives. AB - Synthesis of a new methoxy dibenzofluorene through alkylation, cyclodehydration and aromatization in a one-pot operation is achieved for the first time. Using this hydrocarbon, a few derivatives are prepared through aromatic nitration, catalytic hydrogenation, coupling reaction with a side chain and reduction. The benzylic position of this hydrocarbon with the side chain is oxidized and reduced. Some of these derivatives have demonstrated excellent antitumor activities in vitro. This study confirms antitumor activity depends on the structures of the molecules. PMID- 25136550 TI - Effects of a pragmatic lifestyle intervention for reducing body mass in obese adults with obstructive sleep apnoea: a randomised controlled trial. AB - This study investigated the effects of a pragmatic lifestyle intervention in obese adults with continuous positive airway pressure-treated obstructive sleep apnoea hypopnoea syndrome (OSAHS). Sixty patients were randomised 1 : 1 to either a 12-week lifestyle intervention or an advice-only control group. The intervention involved supervised exercise sessions, dietary advice, and the promotion of lifestyle behaviour change using cognitive-behavioural techniques. Outcomes were assessed at baseline (week 0), intervention end-point (week 13), and follow-up (week 26). The primary outcome was 13-week change in body mass. Secondary outcomes included anthropometry, blood-borne biomarkers, exercise capacity, and health-related quality of life. At end-point, the intervention group exhibited small reductions in body mass (-1.8 [-3.0, -0.5] kg; P = 0.007) and body fat percentage (-1 [-2, 0]%; P = 0.044) and moderate improvements in C reactive protein (-1.3 [-2.4, -0.2] mg.L(-1); P = 0.028) and exercise capacity (95 [50, 139] m; P < 0.001). At follow-up, changes in body mass (-2.0 [-3.5, 0.5] kg; P = 0.010), body fat percentage (-1 [-2, 0]%; P = 0.033), and C-reactive protein (-1.3 [-2.5, -0.1] mg.L(-1); P = 0.037) were maintained and exercise capacity was further improved (132 [90, 175] m; P < 0.001). This trial is registered with ClinicalTrials.gov NCT01546792. PMID- 25136553 TI - Bone tissue engineering and regeneration. PMID- 25136551 TI - The evolving role of radiosurgery in the management of radiation-induced meningiomas: a review of current advances and future directions. AB - Meningiomas are among the most common primary adult brain tumors, which arise either spontaneously or secondary to environmental factors such as ionizing radiation. The latter are referred to as radiation-induced meningiomas (RIMs) which, while much less common than their spontaneous counterparts, are challenging from a management point of view. Similar to spontaneous meningiomas, the optimal management of RIMs is complete surgical resection. However, given their high grade, multiplicity, tendency to invade bone and venous sinuses, and high recurrence rate, this cannot always be accomplished safely. Therefore, other therapeutic modalities, such as stereotactic radiosurgery, have emerged. In the current review, we provide an overview of the historical outcomes achieved for RIMs through radiosurgery and microsurgical resection. Furthermore, we provide a discussion of clinical and radiological parameters that affect the decision making process with regard to the management of RIMs. We also provide an outline of recent changes in our understanding of RIMs, based on molecular and genetic markers, and how these will change our management perspective. We conclude the review by summarizing some of the current obstacles in the management of RIMs with SRS and how current and future research can address these challenges. PMID- 25136552 TI - Alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide improve erectile function, sexual quality of life, and ejaculation function in patients with moderate mild-moderate erectile dysfunction: a prospective, randomized, placebo-controlled, single-blinded study. AB - We aimed to evaluate the efficacy of oral therapy with alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide (Tradamix TX1000) in patients with erectile dysfunction (ED) at 3 months of follow-up. From January 2013 to September 2013, 177 patients diagnosed with mild-moderate ED (IIEF-EF < 26) were enrolled in this multicenter, single-blinded, placebo-controlled study and randomized in Group A (Tradamix, n = 87) and Group B (placebo, n = 90). Penile color Doppler ultrasound measures, IIEF-15 questionnaire, male sexual health questionnaire-ejaculation disorder (MSHQ-EjD), and sexual quality of life (SQoL-M) were collected. We observed significant changes of the IIEF-15 in Group A (mean difference: 11.54; P < 0.05) at 3 months versus Group B (P < 0.05). PSV (P < 0.05), IIEF-intercourse satisfaction (P < 0.05), IIEF-orgasmic function (mean P < 0.05), IIEF-sexual desire (P < 0.05), IIEF-overall satisfaction (P < 0.05), MSHQ-EjD (mean difference: 1.21; P < 0.05), and SQoL-M (mean difference: 10.2; P < 0.05) were significantly changed in Group A versus baseline and Group B. Patients with moderate arterial dysfunction showed significant increase of PSV (P < 0.05), IIEF-EF (P < 0.05), MSHQ-EjD (P < 0.05), and SQoL-M (P < 0.05) in Group A. Therapy with Tradamix improves erectile and ejaculation function and sexual quality of life in patients with mild-moderate ED and in particular for those with moderate arterial dysfunction. PMID- 25136554 TI - The different dose-volume effects of normal tissue complication probability using LASSO for acute small-bowel toxicity during radiotherapy in gynecological patients with or without prior abdominal surgery. AB - PURPOSE: To develop normal tissue complication probability (NTCP) model with least absolute shrinkage and selection operator (LASSO) to analyze dose-volume effects that influence the incidence of acute diarrhea among gynecological patients with/without prior abdominal surgery. METHODS AND MATERIALS: Ninety-five patients receiving gynecologic radiotherapy (RT) were enrolled. The endpoint was defined as the grade 2(+) acute diarrhea toxicity during treatment. We obtained the range of small-bowel volume in V4 Gy to V40 Gy of dose. RESULTS: The number of patients experiencing grade 2(+) acute diarrhea toxicity was 23/61 (38%) in the group without abdominal surgery (group 0) and 17/34 (50%) patients with abdominal surgery (group 1). The most significant predictor was found for the logistic NTCP model with V16 Gy as the cutoff dose for group 0 and V40 Gy for group 1. Logistic regression NTCP model parameters were TV10 ~ 290 cc for V16 Gy and TV10 ~ 75 cc for V40 Gy, respectively. CONCLUSION: To keep the incidence of grade 2(+) acute small-bowel toxicity below 10%, we suggest that small-bowel volume above the prescription dose (V16 Gy) should be held to <290 cc for patients without abdominal surgery, and the prescription dose (V40 Gy) should be maintained <75 cc for patients with abdominal surgery. PMID- 25136556 TI - miRNA signature in mouse spermatogonial stem cells revealed by high-throughput sequencing. AB - Spermatogonial stem cells (SSCs) play fundamental roles in spermatogenesis. Although a handful of genes have been discovered as key regulators of SSC self renewal and differentiation, the regulatory network responsible for SSC function remains unclear. In particular, small RNA signatures during mouse spermatogenesis are not yet systematically investigated. Here, using next generation sequencing, we compared small RNA signatures of in vitro expanded SSCs, testis-derived somatic cells (Sertoli cells), developing germ cells, mouse embryonic stem cells (ESCs), and mouse mesenchymal stem cells among mouse embryonic stem cells (ESCs) to address small RNA transition during mouse spermatogenesis. The results manifest that small RNA transition during mouse spermatogenesis displays overall declined expression profiles of miRNAs and endo-siRNAs, in parallel with elevated expression profiles of piRNAs, resulting in the normal biogenesis of sperms. Meanwhile, several novel miRNAs were preferentially expressed in mouse SSCs, and further investigation of their functional annotation will allow insights into the mechanisms involved in the regulation of SSC activities. We also demonstrated the similarity of miRNA signatures between SSCs and ESCs, thereby providing a new clue to understanding the molecular basis underlying the easy conversion of SSCs to ESCs. PMID- 25136558 TI - Alteration of interictal brain activity in patients with temporal lobe epilepsy in the left dominant hemisphere: a resting-state MEG study. AB - Resting MEG activities were compared between patients with left temporal lobe epilepsy (LTLE) and normal controls. Using SAMg2, the activities of MEG data were reconstructed and normalized. Significantly elevated SAMg2 signals were found in LTLE patients in the left temporal lobe and medial structures. Marked decreases of SAMg2 signals were found in the wide extratemporal lobe regions, such as the bilateral visual cortex. The study also demonstrated a positive correlation between the seizure frequency and brain activities of the abnormal regions after the multiple linear regression analysis. These results suggested that the aberrant brain activities not only were related to the epileptogenic zones, but also existed in other extratemporal regions in patients with LTLE. The activities of the aberrant regions could be further damaged with the increase of the seizure frequency. Our findings indicated that LTLE could be a multifocal disease, including complex epileptic networks and brain dysfunction networks. PMID- 25136555 TI - Modelling cochlear mechanics. AB - The cochlea plays a crucial role in mammal hearing. The basic function of the cochlea is to map sounds of different frequencies onto corresponding characteristic positions on the basilar membrane (BM). Sounds enter the fluid filled cochlea and cause deflection of the BM due to pressure differences between the cochlear fluid chambers. These deflections travel along the cochlea, increasing in amplitude, until a frequency-dependent characteristic position and then decay away rapidly. The hair cells can detect these deflections and encode them as neural signals. Modelling the mechanics of the cochlea is of help in interpreting experimental observations and also can provide predictions of the results of experiments that cannot currently be performed due to technical limitations. This paper focuses on reviewing the numerical modelling of the mechanical and electrical processes in the cochlea, which include fluid coupling, micromechanics, the cochlear amplifier, nonlinearity, and electrical coupling. PMID- 25136559 TI - Analysis of genotype 1b hepatitis C virus IRES in serum and peripheral blood mononuclear cells in patients treated with interferon and ribavirin. AB - Hepatitis C virus (HCV) highly conserved IRES (internal ribosome entry site) sequence, localized within the 5(')-untranslated region (5(')UTR), may determine viral properties like replication efficiency and cell tropism. The aim of the present study was to characterize newly emerging 5(')UTR variants in serum and peripheral blood mononuclear cells (PBMC) in chronic hepatitis C patients treated with interferon (IFN) and ribavirin and to identify their effect on IRES secondary structures. The study group consisted of 87 patients infected with genotype 1b from whom serum and PBMC samples were collected at 9 time points (before, during, and after treatment). New 5(')UTR variants developed in 9 patients. Out of the overall 14 new variants, 9 (64%) were found in PBMC. HCV variants with decreased thermodynamic stability were identified only in PBMC and C183U mutation was the most common one in this compartment. In conclusion, antiviral treatment may favor emergence of new 5(')UTR variants both in blood and in PBMC compartments. However, variants developing in the latter compartment were predicted to have lower thermodynamic stability of the IRES secondary structures compared to serum strains. C-U change in position 183, which has not been described previously, might indicate viral adaptation to lymphoid cells. PMID- 25136557 TI - Influence of electric, magnetic, and electromagnetic fields on the circadian system: current stage of knowledge. AB - One of the side effects of each electrical device work is the electromagnetic field generated near its workplace. All organisms, including humans, are exposed daily to the influence of different types of this field, characterized by various physical parameters. Therefore, it is important to accurately determine the effects of an electromagnetic field on the physiological and pathological processes occurring in cells, tissues, and organs. Numerous epidemiological and experimental data suggest that the extremely low frequency magnetic field generated by electrical transmission lines and electrically powered devices and the high frequencies electromagnetic radiation emitted by electronic devices have a potentially negative impact on the circadian system. On the other hand, several studies have found no influence of these fields on chronobiological parameters. According to the current state of knowledge, some previously proposed hypotheses, including one concerning the key role of melatonin secretion disruption in pathogenesis of electromagnetic field induced diseases, need to be revised. This paper reviews the data on the effect of electric, magnetic, and electromagnetic fields on melatonin and cortisol rhythms-two major markers of the circadian system as well as on sleep. It also provides the basic information about the nature, classification, parameters, and sources of these fields. PMID- 25136560 TI - Evaluation of the influence of formulation and process variables on mechanical properties of oral mucoadhesive films using multivariate data analysis. AB - Oral mucosa is an attractive region for the local and systemic application of many drugs. Oral mucoadhesive films are preferred for their prolonged time of residence, the improved bioavailability of the drug they contain, their painless application, their protection against lesions, and their nonirritating properties. This work was focused on preparation of nonmedicated carmellose-based films using both solvent casting and impregnation methods, respectively. Moreover, a modern approach to evaluation of mucoadhesive films applying analysis of texture and subsequent multivariate data analysis was used. In this experiment, puncture strength strongly correlated with tensile strength and could be used to obtain necessary information about the mechanical film characteristics in films prepared using both methods. Puncture work and tensile work were not correlated in films prepared using the solvent casting method, as increasing the amount of glycerol led to an increase in the puncture work in thinner films. All measured texture parameters in films prepared by impregnation were significantly smaller compared to films prepared by solvent casting. Moreover, a relationship between the amount of glycerol and film thickness was observed, and a greater recalculated tensile/puncture strength was needed for an increased thickness in films prepared by impregnation. PMID- 25136562 TI - Estimates of the number of people living with HIV in Italy. AB - Objective. To estimate the HIV prevalence and the number of people living with HIV (PLHIV) in Italy with a projection for 2020. Methods. Two methods elaborated by Joint United Nations Programme on HIV/AIDS (UNAIDS) were used: Estimate and Projection Package and Spectrum. Results. A total of 123,000 (115,000-145,000) individuals aged 15 or more were estimated to be living with HIV in Italy at the end of 2012 and the estimated HIV prevalence was 0.28 (0.24-0.32) per 100 residents aged 15 or more. In 2012, the estimated number of new HIV infections among adults was 3,000 (2,700-4,000), and the number of adults in need for ART was 93,000 (80,000-110,000). The projection estimates that 130,000 (110,000 150,000) adults will live with HIV/AIDS in 2020 in Italy. Conclusion. Estimates of PLHIV in Italy stress the high number of PLHIV in need of care and treatment, as well as the need for more information and prevention campaigns. PMID- 25136561 TI - Structural insight into the DNA-binding mode of the primosomal proteins PriA, PriB, and DnaT. AB - Replication restart primosome is a complex dynamic system that is essential for bacterial survival. This system uses various proteins to reinitiate chromosomal DNA replication to maintain genetic integrity after DNA damage. The replication restart primosome in Escherichia coli is composed of PriA helicase, PriB, PriC, DnaT, DnaC, DnaB helicase, and DnaG primase. The assembly of the protein complexes within the forked DNA responsible for reloading the replicative DnaB helicase anywhere on the chromosome for genome duplication requires the coordination of transient biomolecular interactions. Over the last decade, investigations on the structure and mechanism of these nucleoproteins have provided considerable insight into primosome assembly. In this review, we summarize and discuss our current knowledge and recent advances on the DNA binding mode of the primosomal proteins PriA, PriB, and DnaT. PMID- 25136564 TI - Changes in biochemical characteristics and activities of ripening associated enzymes in mango fruit during the storage at different temperatures. AB - As a part of the study to explore the possible strategy for enhancing the shelf life of mango fruits, we investigated the changes in biochemical parameters and activities of ripening associated enzymes of Ashwina hybrid mangoes at 4-day regular intervals during storage at -10 degrees C, 4 degrees C, and 30 +/- 1 degrees C. Titratable acidity, vitamin C, starch content, and reducing sugar were higher at unripe state and gradually decreased with the increasing of storage time at all storage temperatures while phenol content, total soluble solid, total sugar, and nonreducing sugar contents gradually increased. The activities of amylase, alpha-mannosidase, alpha-glucosidase, and invertase increased sharply within first few days and decreased significantly in the later stage of ripening at 30 +/- 1 degrees C. Meanwhile polyphenol oxidase, beta-galactosidase, and beta hexosaminidase predominantly increased significantly with the increasing days of storage till later stage of ripening. At -10 degrees C and 4 degrees C, the enzymes as well as carbohydrate contents of storage mango changed slightly up to 4 days and thereafter the enzyme became fully dormant. The results indicated that increase in storage temperature and time correlated with changes in biochemical parameters and activities of glycosidases suggested the suppression of beta galactosidase and beta-hexosaminidase might enhance the shelf life of mango fruits. PMID- 25136563 TI - Effects of parity and serum prolactin levels on the incidence and regression of DMBA-induced tumors in OFA hr/hr rats. AB - Prolactin (PRL) is a key player in the development of mammary cancer. We studied the effects of parity or hyperprolactinemia on mammary carcinogenesis in OFA hr/hr treated with 7,12-dimethylbenzanthracene. They were divided into three groups: nulliparous (Null), primiparous (PL, after pregnancy and lactation), and hyperprolactinemic rats (I, implanted in the arcuate nucleus with 17beta estradiol). The tumor incidence was similar in the three groups. However, a higher percentage of regressing tumors was evident in the PL group. Serum PRL, mammary development, and mammary beta-casein content were higher in I rats compared to Null. The expression of hormone receptors was similar in the different groups. However, mammary tissue from PL rats bearing tumors had increased expression of PRL and estrogen alpha receptors compared to rats free of tumors. Our results suggest that serum PRL levels do not have relevance on the incidence of tumors, probably because the low levels of PRL in OFA rats are not further decreased by PL like in other strains. However, supraphysiological levels of PRL affect carcinogenesis. PL induces regression of the tumors due to the differentiation produced on the mammary cells. Alterations in the expression of hormonal receptors may be involved in progression and regression of tumors. PMID- 25136565 TI - Recent advances in polyamine metabolism and abiotic stress tolerance. AB - Global warming is an alarming problem in agriculture and its effect on yield loss has been estimated to be five per cent for every degree centigrade rise in temperature. Plants exhibit multiple mechanisms like optimizing signaling pathway, involvement of secondary messengers, production of biomolecules specifically in response to stress, modulation of various metabolic networks in accordance with stress, and so forth, in order to overcome abiotic stress factors. Many structural genes and networks of pathway were identified and reported in plant systems for abiotic stress tolerance. One such crucial metabolic pathway that is involved in normal physiological function and also gets modulated during stress to impart tolerance is polyamine metabolic pathway. Besides the role of structural genes, it is also important to know the mechanism by which these structural genes are regulated during stress. Present review highlights polyamine biosynthesis, catabolism, and its role in abiotic stress tolerance with special reference to plant systems. Additionally, a system based approach is discussed as a potential strategy to dissect the existing variation in crop species in unraveling the interacting regulatory components/genetic determinants related to PAs mediated abiotic stress tolerance. PMID- 25136567 TI - Cell death in human health and disease. PMID- 25136566 TI - Protective effect of ethanolic extract of Tabernaemontana divaricata (L.) R. Br. against DEN and Fe NTA induced liver necrosis in Wistar Albino rats. AB - This study is an attempt to evaluate the hepatoprotective activity of Tabernaemontana divaricata against DEN and Fe NTA induced liver necrosis in rats. Ethanolic extract of the whole plant of Tabernaemontana divaricata at doses of 200 and 400 mg/kg body weight and 5-fluorouracil (standard drug) was orally administered to male Wistar Albino rats once daily for 24 weeks, simultaneously treated with the carcinogen DEN and Fe NTA. In simultaneously treated animals, the plant extract significantly decreased the levels of uric acid, bilirubin, AST, ALT, and ALP in serum and increased the levels of liver marker enzymes in liver. Treatment with the extracts resulted in a significant increase in the levels of antioxidants accompanied by a marked reduction in the levels of malondialdehyde when compared to DEN and Fe NTA treated group. When compared with 200 mg/kg bw rats, 400 mg/kg bw rats and 5-fluorouracil treated rats showed better results in all the parameters. The histopathological studies confirmed the protective effects of extract against DEN and Fe NTA induced liver necrosis. Thus, it could be concluded that the use of Tabernaemontana divaricata extract in the treatment of carcinogen induced hepatic necrosis. PMID- 25136569 TI - Effects of parathyroid hormone on calcium ions in rat bone marrow mesenchymal stem cells. AB - The present study was conducted in order to explore the mechanisms whereby parathyroid hormone (PTH) maintains in vitro proliferation of bone marrow mesenchymal stem cells (BMSCs). Bone marrow was isolated from Sprague Dawley (SD) rat femurs, cultured in vitro, and passaged using a cell adherent culture method. The BMSC proliferation was evaluated by the methyl thiazolyl tetrazolium (MTT) assay and the fluorescence intensity of calcium ions in BMSCs was analyzed by laser scanning confocal microscopy (LSCM). Our results show that BMSC proliferation in the experimental group treated with PTH was more significant than controls. The calcium ion fluorescence intensity in BMSCs was significantly higher for the experimental group as compared to the control group. For each group, there was significant difference in the fluorescence intensity of calcium ions in BMSCs between 7 d and 14 d. In conclusion, parathyroid hormone increased the fluorescence intensity of calcium ions in BMSCs, which might represent a key mechanism whereby BMSC proliferation is maintained. PMID- 25136568 TI - Clinical applications of platelet-rich plasma in patellar tendinopathy. AB - Platelet-rich plasma (PRP), a blood derivative with high concentrations of platelets, has been found to have high levels of autologous growth factors (GFs), such as transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), fibroblastic growth factor (FGF), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). These GFs and other biological active proteins of PRP can promote tissue healing through the regulation of fibrosis and angiogenesis. Moreover, PRP is considered to be safe due to its autologous nature and long-term usage without any reported major complications. Therefore, PRP therapy could be an option in treating overused tendon damage such as chronic tendinopathy. Here, we present a systematic review highlighting the clinical effectiveness of PRP injection therapy in patellar tendinopathy, which is a major cause of athletes to retire from their respective careers. PMID- 25136570 TI - Effects of crude extracts from medicinal herbs Rhazya stricta and Zingiber officinale on growth and proliferation of human brain cancer cell line in vitro. AB - Hitherto, limited clinical impact has been achieved in the treatment of glioblastoma (GBMs). Although phytochemicals found in medicinal herbs can provide mankind with new therapeutic remedies, single agent intervention has failed to bring the expected outcome in clinical trials. Therefore, combinations of several agents at once are gaining increasing attractiveness. In the present study, we investigated the effects of crude alkaloid (CAERS) and flavonoid (CFEZO) extracts prepared from medicinal herbs, Rhazya stricta and Zingiber officinale, respectively, on the growth of human GBM cell line, U251. R. stricta and Z. officinale are traditionally used in folkloric medicine and have antioxidant, anticarcinogenic, and free radical scavenging properties. Combination of CAERS and CFEZO treatments synergistically suppressed proliferation and colony formation and effectively induced morphological and biochemical features of apoptosis in U251 cells. Apoptosis induction was mediated by release of mitochondrial cytochrome c, increased Bax : Bcl-2 ratio, enhanced activities of caspase-3 and -9, and PARP-1 cleavage. CAERS and CFEZO treatments decreased expression levels of nuclear NF-kappaBp65, survivin, XIAP, and cyclin D1 and increased expression level of p53, p21, and Noxa. These results suggest that combination of CAERS and CFEZO provides a useful foundation for studying and developing novel chemotherapeutic agents for the treatment of GBM. PMID- 25136571 TI - Recognition of 27-class protein folds by adding the interaction of segments and motif information. AB - The recognition of protein folds is an important step for the prediction of protein structure and function. After the recognition of 27-class protein folds in 2001 by Ding and Dubchak, prediction algorithms, prediction parameters, and new datasets for the prediction of protein folds have been improved. However, the influences of interactions from predicted secondary structure segments and motif information on protein folding have not been considered. Therefore, the recognition of 27-class protein folds with the interaction of segments and motif information is very important. Based on the 27-class folds dataset built by Liu et al., amino acid composition, the interactions of secondary structure segments, motif frequency, and predicted secondary structure information were extracted. Using the Random Forest algorithm and the ensemble classification strategy, 27 class protein folds and corresponding structural classification were identified by independent test. The overall accuracy of the testing set and structural classification measured up to 78.38% and 92.55%, respectively. When the training set and testing set were combined, the overall accuracy by 5-fold cross validation was 81.16%. In order to compare with the results of previous researchers, the method above was tested on Ding and Dubchak's dataset which has been widely used by many previous researchers, and an improved overall accuracy 70.24% was obtained. PMID- 25136572 TI - High potential source for biomass degradation enzyme discovery and environmental aspects revealed through metagenomics of Indian buffalo rumen. AB - The complex microbiomes of the rumen functions as an effective system for plant cell wall degradation, and biomass utilization provide genetic resource for degrading microbial enzymes that could be used in the production of biofuel. Therefore the buffalo rumen microbiota was surveyed using shot gun sequencing. This metagenomic sequencing generated 3.9 GB of sequences and data were assembled into 137270 contiguous sequences (contigs). We identified potential 2614 contigs encoding biomass degrading enzymes including glycoside hydrolases (GH: 1943 contigs), carbohydrate binding module (CBM: 23 contigs), glycosyl transferase (GT: 373 contigs), carbohydrate esterases (CE: 259 contigs), and polysaccharide lyases (PE: 16 contigs). The hierarchical clustering of buffalo metagenomes demonstrated the similarities and dissimilarity in microbial community structures and functional capacity. This demonstrates that buffalo rumen microbiome was considerably enriched in functional genes involved in polysaccharide degradation with great prospects to obtain new molecules that may be applied in the biofuel industry. PMID- 25136573 TI - Designing peptide-based HIV vaccine for Chinese. AB - CD4+ T cells are central to the induction and maintenance of CD8+ T cell and antibody-producing B cell responses, and the latter are essential for the protection against disease in subjects with HIV infection. How to elicit HIV specific CD4+ T cell responses in a given population using vaccines is one of the major areas of current HIV vaccine research. To design vaccine that targets specifically Chinese, we assembled a database that is comprised of sequences from 821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles identified in Chinese population. We then predicted 20 potential HIV epitopes using bioinformatics approaches. The combination of these 20 epitopes has a theoretical coverage of 98.1% of the population for both the prevalent HIV genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine experimentally will facilitate the development of a CD4+ T cell vaccine especially catered for Chinese. PMID- 25136574 TI - Monte Carlo simulation of protein adsorption on energetically heterogeneous surfaces. AB - The modified triangular-well potential model was applied to incorporate the effect of surface energy on the adsorption of particles or proteins on energetically heterogeneous surfaces. The method is convenient in simulating the adsorption on heterogeneous surface of which different region possesses different free energy. Spherical particles with attractive forces were added on the surface and underwent surface diffusion before they were quenched in place. It was seen that the ratio of surface energies of two regions had to be greater than 10 in order to simulate the adsorption in which the particles were selectively adsorbed on a favorable area. At a fixed ratio of surface energies, the obtained structures were similar. If the ratio was less than 10, the probability of adsorption on any site on the surface was not much different so the adsorption would be homogeneous adsorption. The method, thus, could be applied widely to simulate the adsorption of various conditions. PMID- 25136577 TI - Gender and family disparities in suicide attempt and role of socioeconomic, school, and health-related difficulties in early adolescence. AB - Suicide attempt (SA) is common in early adolescence and the risk may differ between boys and girls in nonintact families partly because of socioeconomic, school, and health-related difficulties. This study explored the gender and family disparities and the role of these covariates. Questionnaires were completed by 1,559 middle-school adolescents from north-eastern France including sex, age, socioeconomic factors (family structure, nationality, parents' education, father's occupation, family income, and social support), grade repetition, depressive symptoms, sustained violence, sexual abuse, unhealthy behaviors (tobacco/alcohol/cannabis/hard drug use), SA, and their first occurrence over adolescent's life course. Data were analyzed using Cox regression models. SA affected 12.5% of girls and 7.2% of boys (P < 0.001). The girls living with parents divorced/separated, in reconstructed families, and with single parents had a 3-fold higher SA risk than those living in intact families. Over 63% of the risk was explained by socioeconomic, school, and health-related difficulties. No family disparities were observed among boys. Girls had a 1.74 time higher SA risk than boys, and 45% of the risk was explained by socioeconomic, school, and mental difficulties and violence. SA prevention should be performed in early adolescence and consider gender and family differences and the role of socioeconomic, school, and health-related difficulties. PMID- 25136576 TI - Novel hypoxanthine guanine phosphoribosyltransferase gene mutations in Saudi Arabian hyperuricemia patients. AB - Over the past decade, a steady increase in the incidence of HPRT-related hyperuricemia (HRH) has been observed in Saudi Arabia. We examined all the nine exons of HPRT gene for mutations in ten biochemically confirmed hyperuricemia patients, including one female and three normal controls. In all, we identified 13 novel mutations in Saudi Arabian HPRT-related hyperuricemia patients manifesting different levels of uric acid. The Lys103Met alteration was highly recurrent and was observed in 50% of the cases, while Ala160Thr and Lys158Asn substitutions were found in two patients. Moreover, in 70% of the patients >=2 mutations were detected concurrently in the HPRT gene. Interestingly, one of the patients that harbored Lys103Met substitution along with two frameshift mutations at codons 85 and 160 resulting in shortened protein demonstrated unusually high serum uric acid level of 738 MUmol/L. Two of the seven point mutations that resulted in amino acid change (Lys103Met and Val160Gly) were predicted to be damaging by SIFT and Polyphen and were further analyzed for their protein stability and function by molecular dynamics simulation. The identified novel mutations in the HPRT gene may prove useful in the prenatal diagnosis and genetic counseling. PMID- 25136575 TI - Vagus nerve through alpha7 nAChR modulates lung infection and inflammation: models, cells, and signals. AB - Cholinergic anti-inflammatory pathway (CAP) bridges immune and nervous systems and plays pleiotropic roles in modulating inflammation in animal models by targeting different immune, proinflammatory, epithelial, endothelial, stem, and progenitor cells and signaling pathways. Acute lung injury (ALI) is a devastating inflammatory disease. It is pathogenically heterogeneous and involves many cells and signaling pathways. Here, we emphasized the research regarding the modulatory effects of CAP on animal models, cell population, and signaling pathways that involved in the pathogenesis of ALI. By comparing the differential effects of CAP on systemic and pulmonary inflammation, we postulated that a pulmonary parasympathetic inflammatory reflex is formed to sense and respond to pathogens in the lung. Work targeting the formation and function of pulmonary parasympathetic inflammatory reflex would extend our understanding of how vagus nerve senses, recognizes, and fights with pathogens and inflammatory responses. PMID- 25136578 TI - Potassium channel ether a go-go1 is aberrantly expressed in human liposarcoma and promotes tumorigenesis. AB - The ether a go-go1 (Eag1) channel is overexpressed in a variety of cancers. However, the expression and function of Eag1 in liposarcoma are poorly understood. In the present study, the mRNA expression of Eag1 in different adipose tissue samples was examined by real-time PCR. Then, the protein expression of Eag1 in 131 different adipose tissues from 109 patients was detected by immunohistochemistry. Next, the associations between Eag1 expression and clinicopathological features of liposarcoma were analyzed. In addition, the effects of Eag1 on liposarcoma cell proliferation and cycle were evaluated by CCK 8, colony formation, xenograft mouse model, and flow cytometry, respectively. Finally, the activation of p38 mitogen-activated protein kinase (MAPK) was detected by Western blot analysis to explain the detailed mechanisms of oncogenic potential of Eag1 in liposarcoma. It was found that Eag1 was aberrantly expressed in over 67% liposarcomas, with a higher frequency than in lipoma, hyperplasia, inflammation, and normal adipose tissues. However, Eag1 expression was not correlated with clinicopathological features of liposarcoma. Eag1 inhibitor imipramine or Eag1-shRNA significantly suppressed the proliferation of liposarcoma cells in vitro and in vivo, accompanying with accumulation of cells in the G1 phase. These results suggest that Eag1 plays an important role in regulating the proliferation and cell cycle of liposarcoma cells and might be a potential therapeutic target for liposarcoma. PMID- 25136579 TI - Management of poor responders in IVF: is there anything new? AB - Despite the fact that in the last two decades an enormous number of papers on the topic of poor ovarian response have been published in the literature, so far it has been impossible to identify any efficient treatment to improve the ovarian response and the clinical outcome of this group of patients. The incidence of poor ovarian responders among infertile women has been estimated at 9-24% but according to recent reviews, it seems to have slightly increased. The limitation in quantifying the incidence of these patients among the infertile population is due to the difficulty of a clear definition in literature. A recent paper by the Bologna ESHRE working group on poor ovarian response has been the first real attempt to find a common definition. Current literature proposes new risk factors which could be the cause of a reduction in ovarian reserve, which also includes genetic factors. This represents the first necessary step towards finding applicable solutions for these patients. To date, there is a substantial lack of literature that identifies an ideal protocol for these patients. The use of the "Bologna criteria" and the introduction of long acting gonadotropin in clinical practice have given rise to new promising stimulation protocols for this group of patients. PMID- 25136581 TI - High molecular weight proteins of Trypanosoma cruzi reduce cross-reaction with Leishmania spp. in serological diagnosis tests. AB - Chagas disease is caused by the parasite Trypanosoma cruzi. Because of its distribution throughout Latin America, sometimes it can overlap with other parasitic diseases, such as leishmaniasis, caused by Leishmania spp. This might represent a problem when performing serological diagnosis, because both parasites share antigens, resulting in cross-reactions. In the present work we evaluated Mexican sera samples: 83.8% of chagasic patients recognized at least one antigen of high molecular weight (>95 kDa) when evaluated by Western blot. Proteins of 130 kDa and 160 kDa are predominantly being recognized by asymptomatic chagasic patients. When the proteins were extracted using Triton X-100 detergent, a larger number of specific T. cruzi proteins were obtained. This protein fraction can be used to increase specificity to 100% in Western blot assays without losing sensitivity of the test. High molecular weight proteins of T. cruzi include glycoproteins with a great amount of alphaMan (alpha-mannose), alphaGlc (alpha glucose), GlcNAc (N-acetylglucosamine), and alphaGal (alpha-galactose) content and these structures play an essential role in antigens recognition by antibodies present in patients' sera. PMID- 25136580 TI - The study of fetal rat model of intra-amniotic isoproterenol injection induced heart dysfunction and phenotypic switch of contractile proteins. AB - To establish a reliable isoproterenol induced heart dysfunction fetal rat model and understand the switches of contractile proteins, 45 pregnant rats were divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated twice, and control groups. And 18 adult rats were divided into isoproterenol treated and control groups. H&E staining, Masson staining, and transmission electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7 day continuous intraperitoneal injections were performed for adults. Then echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks later, respectively. Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart dysfunction were opposite to adult procedure. The administration of intra amniotic isoproterenol to fetal rats could induce heart dysfunction and the regulation of contractile proteins of fetuses was different from adult procedure. PMID- 25136582 TI - Proton-based stereotactic ablative radiotherapy in early-stage non-small-cell lung cancer. AB - Stereotactic ablative radiotherapy (SABR), a recent implementation in the practice of radiation oncology, has been shown to confer high rates of local control in the treatment of early stage non-small-cell lung cancer (NSCLC). This technique, which involves limited invasive procedures and reduced treatment intervals, offers definitive treatment for patients unable or unwilling to undergo an operation. The use of protons in SABR delivery confers the added physical advantage of normal tissue sparing due to the absence of collateral radiation dose delivered to regions distal to the target. This may translate into clinical benefit and a decreased risk of clinical toxicity in patients with nearby critical structures or limited pulmonary reserve. In this review, we present the rationale for proton-based SABR, principles relating to the delivery and planning of this modality, and a summary of published clinical studies. PMID- 25136583 TI - Rho GTPase-activating protein 35 rs1052667 polymorphism and osteosarcoma risk and prognosis. AB - The Rho GTPase-activating protein 35 (ARHGAP35), an important Rho family GTPase activating protein, may be associated with tumorigenesis of some tumors. Here, we investigated the relationship between an important polymorphic variant at 3'-UTR of this gene (rs1052667) and osteosarcoma risk and prognosis. This hospital-based case-control study, including 247 osteosarcoma patients and 428 age-, sex-, and race-matched healthy controls, was conducted in Guangxi population. Genotypes were tested using TaqMan PCR technique. We found a significant difference in the frequency of rs1052667 genotypes between cases and controls. Compared with the homozygote of rs1052667 C alleles (rs1052667-CC), the genotypes with rs1052667 T alleles (namely, rs1052667-CT or -TT) increased osteosarcoma risk (odds ratios: 2.41 and 7.35, resp.). Moreover, rs1052667 polymorphism was correlated with such pathological features of osteosarcoma as tumor size, tumor grade, and tumor metastasis. Additionally, this polymorphism also modified the overall survival and recurrence-free survival of osteosarcoma cases. Like tumor grade, ARHGAP35 rs1052667 polymorphism was an independent prognostic factor influencing the survival of osteosarcoma. These results suggest that ARHGAP35 rs1052667 polymorphism may be associated with osteosarcoma risk and prognosis. PMID- 25136584 TI - Effect of exercise intensity on isoform-specific expressions of NT-PGC-1 alpha mRNA in mouse skeletal muscle. AB - PGC-1alpha is an inducible transcriptional coactivator that regulates mitochondrial biogenesis and cellular energy metabolism in skeletal muscle. Recent studies have identified two additional PGC-1alpha transcripts that are derived from an alternative exon 1 (exon 1b) and induced by exercise. Given that the PGC-1alpha gene also produces NT-PGC-1alpha transcript by alternative 3(') splicing between exon 6 and exon 7, we have investigated isoform-specific expression of NT-PGC-1alpha mRNA in mouse skeletal muscle during physical exercise with different intensities. We report here that NT-PGC-1alpha-a mRNA expression derived from a canonical exon 1 (exon 1a) is increased by high intensity exercise and AMPK activator AICAR in mouse skeletal muscle but not altered by low- and medium-intensity exercise and beta 2-adrenergic receptor agonist clenbuterol. In contrast, the alternative exon 1b-driven NT-PGC-1alpha-b (PGC-1alpha4) and NT-PGC-1alpha-c are highly induced by low-, medium-, and high intensity exercise, AICAR, and clenbuterol. Ectopic expression of NT-PGC-1alpha-a in C2C12 myotube cells upregulates myosin heavy chain (MHC I, MHC II a) and Glut4, which represent oxidative fibers, and promotes the expression of mitochondrial genes (Cyc1, COX5B, and ATP5B). In line with gene expression data, citrate synthase activity was significantly increased by NT-PGC-1alpha-a in C2C12 myotube cells. Our results indicate the regulatory role for NT-PGC-1alpha-a in mitochondrial biogenesis and adaptation of skeletal muscle to endurance exercise. PMID- 25136586 TI - New drugs on the Internet: the case of Camfetamine. AB - INTRODUCTION: The number of new psychoactive substances (NPS) advertised for sale online is constantly increasing and it has become a phenomenon of global concern. Among NPS, Camfetamine has been rediscovered as recreational drug in 2011. Very little information is still available in the scientific literature on its nature and potential health risks. METHODS: Data in scientific literature were integrated with a multilingual qualitative assessment of a range of online resources over the period of 32 months (May 2011-January 2014). RESULTS: N-Methyl 3-phenyl-norbornan-2-amine (Camfetamine) may act as an indirect dopaminergic agonist in the central nervous system and may have mild-moderate opioid activity too. There are no current epidemiological data about recreational use of Camfetamine; our research shows that it is indeed used especially by individuals with a history of recreational polydrug misuse. It facilitates mental alertness, induces relaxation, and, unlike many other stimulants, seems not to be associated with severe physical effects. Valid causes for concern issued in our research may be Camfetamine intravenous or intramuscular administration as well as its use in conjunction with other psychoactive substances. CONCLUSIONS: It is here highlighted that more large-scale studies need to be carried out to confirm and better describe both the extent of Camfetamine misuse and possible psychotropic/adverse effects. PMID- 25136587 TI - Diversity and enzymatic profiling of halotolerant micromycetes from Sebkha El Melah, a Saharan salt flat in southern Tunisia. AB - Twenty-one moderately halotolerant fungi have been isolated from sample ashes collected from Sebkha El Melah, a Saharan salt flat located in southern Tunisia. Based on morphology and sequence inference from the internal transcribed spacer regions, 28S rRNA gene and other specific genes such as beta-tubulin, actin, calmodulin, and glyceraldehyde-3-phosphate dehydrogenase, the isolates were found to be distributed over 15 taxa belonging to 6 genera of Ascomycetes: Cladosporium (n = 3), Alternaria (n = 4), Aspergillus (n = 3), Penicillium (n = 5), Ulocladium (n = 2), and Engyodontium (n = 2). Their tolerance to different concentrations of salt in solid and liquid media was examined. Excepting Cladosporium cladosporioides JA18, all isolates were considered as alkali-halotolerant since they were able to grow in media containing 10% of salt with an initial pH 10. All isolates were resistant to oxidative stresses and low temperature whereas 5 strains belonging to Alternaria, Ulocladium, and Aspergillus genera were able to grow at 45 degrees C. The screening of fungal strains for sets of enzyme production, namely, cellulase (CMCase), amylase, protease, lipase, and laccase, in presence of 10% NaCl, showed a variety of extracellular hydrolytic and oxidative profiles. Protease was the most abundant enzyme produced whereas laccase producers were members of the genus Cladosporium. PMID- 25136585 TI - Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. AB - Hypertension is a complex condition and is the most common cardiovascular risk factor, contributing to widespread morbidity and mortality. Approximately 90% of hypertension cases are classified as essential hypertension, where the precise cause is unknown. Hypertension is associated with inflammation; however, whether inflammation is a cause or effect of hypertension is not well understood. The purpose of this review is to describe evidence from human and animal studies that inflammation leads to the development of hypertension, as well as the evidence for involvement of oxidative stress and endothelial dysfunction--both thought to be key steps in the development of hypertension. Other potential proinflammatory conditions that contribute to hypertension-such as activation of the sympathetic nervous system, aging, and elevated aldosterone--are also discussed. Finally, we consider the potential benefit of anti-inflammatory drugs and statins for antihypertensive therapy. The evidence reviewed suggests that inflammation can lead to the development of hypertension and that oxidative stress and endothelial dysfunction are involved in the inflammatory cascade. Aging and aldosterone may also both be involved in inflammation and hypertension. Hence, in the absence of serious side effects, anti-inflammatory drugs could potentially be used to treat hypertension in the future. PMID- 25136588 TI - Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer. AB - Autophagy is dysregulated in cancer and might be involved in ovarian carcinogenesis. BECLIN-1, a protein that interacts with either BCL-2 or PI3k class III, plays a critical role in the regulation of both autophagy and cell death. Induction of autophagy is associated with the presence of vacuoles characteristically labelled with the protein LC3. We have studied the biological and clinical significance of BECLIN 1 and LC3 in ovary tumours of different histological types. The positive expression of BECLIN 1 was well correlated with the presence of LC3-positive autophagic vacuoles and was inversely correlated with the expression of BCL-2. The latter inhibits the autophagy function of BECLIN 1. We found that type I tumours, which are less aggressive than type II, were more frequently expressing high level of BECLIN 1. Of note, tumours of histologic grade III expressed low level of BECLIN 1. Consistently, high level of expression of BECLIN 1 and LC3 in tumours is well correlated with the overall survival of the patients. The present data are compatible with the hypotheses that a low level of autophagy favours cancer progression and that ovary cancer with upregulated autophagy has a less aggressive behaviour and is more responsive to chemotherapy. PMID- 25136589 TI - Event-specific risk factors predicting episodes of unprotected anal intercourse with male nonregular partners among men who have sex with men using case crossover study design. AB - This study investigated event-specific factors that determine episodes of unprotected and protected anal intercourse (UAI and PAI) among 215 men who have sex with men (MSM), who used condoms inconsistently with nonregular partners (NRP) in the last six months, in Hong Kong. A case-crossover study design was used. Lower likelihood of episodes involving UAI with NRP was associated with (1) five partner attributes (NRP were <35 years old, at least three previous anal sex experiences with the NRP, perception that participant and the NRP had asymmetrical sexual experience, perception that the NRP was feminine, and liking toward the NRP; OR = 0.16-0.52), (2) six situational variables (the participant having had UAI with another man in the last week, having discussed condom use, perception that the NRP liked to use condom, partner's suggestion to have PAI, participant's suggestion to have PAI, and participant's plan to use condoms; OR = 0.11-0.39), and (3) four environmental/setting variables (condoms already placed at the venue, display of condom use promotion materials, participant's possession of a condom, and the NRP possessed a condom; OR = 0.27-0.45). HIV prevention targeting MSM should focus on event-specific protective factors, which may be different from those obtained from studies distinguishing condom users versus nonusers. PMID- 25136590 TI - Methylamine-sensitive amperometric biosensor based on (His)6-tagged Hansenula polymorpha methylamine oxidase immobilized on the gold nanoparticles. AB - A novel methylamine-selective amperometric bienzyme biosensor based on recombinant primary amine oxidase isolated from the recombinant yeast strain Saccharomyces cerevisiae and commercial horseradish peroxidase is described. Two amine oxidase preparations were used: free enzyme (AMO) and covalently immobilized on the surface of gold nanoparticles (AMO-nAu). Some bioanalytical parameters (sensitivity, selectivity, and storage stability) of the developed biosensors were investigated. The sensitivity for both sensors is high: 1450 +/- 113 and 700 +/- 30 A(-1) .M(-1) .m(-2) for AMO-nAu biosensor, respectively. The biosensors exhibit the linear range from 15 MUM to 150 MUM (AMO-nAu) and from 15 MUM to 60 MUM (AMO). The developed biosensor demonstrated a good selectivity toward methylamine (MA) (signal for dimethylamine and trimethylamine is less than 5% and for ethylamine 15% compared to MA output) and reveals a satisfactory storage stability. The constructed amperometric biosensor was used for MA assay in real samples of fish products in comparison with chemical method. The values obtained with both approaches different methods demonstrated a high correlation. PMID- 25136591 TI - The effect of Babesia divergens infection on the spleen of Mongolian gerbils. AB - Babesiosis is caused by intraerythrocytic protozoan parasites transmitted by ticks and affects a wide range of domestic and wild animals and occasionally humans. The current study aimed to investigate the effect of B. divergens infected erythrocytes on spleen histopathology, cell cycle alteration, and the presence of oxidative stress. Mongolian gerbils were challenged with 5 * 10(6) Babesia divergens infected erythrocytes. Parasitemia reached approximately 77% at day 5 postinfection. Infection also induced injury of the spleen. This was evidenced with (i) increases in cellular damage of the spleen, (ii) decrease in antioxidant capacity as indicated by decreased glutathione, catalase, and superoxide dismutase levels, (iii) increased production of malondialdehyde and nitric oxide derived products (nitrite/nitrate), and (iv) increased lactic acid dehydrogenase activity and protein carbonyl content in the spleen. Infection interfered with normal cell cycle of the spleen cells at G0/G1, S, and G2/M phases. On the basis of the above results it can be hypothesized that B. divergens infected erythrocytes could alter the spleen histopathology and cause cell cycle alteration and induce oxidative stress in splenic tissue. PMID- 25136592 TI - Automated synthesis of 18F-fluoropropoxytryptophan for amino acid transporter system imaging. AB - OBJECTIVE: This study was to develop a cGMP grade of [(18)F]fluoropropoxytryptophan ((18)F-FTP) to assess tryptophan transporters using an automated synthesizer. METHODS: Tosylpropoxytryptophan (Ts-TP) was reacted with K(18)F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18 column, methanol : water = 7 : 3) analyses. In vitro cellular uptake of (18)F-FTP and (18)F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with (18)F-FTP and (18)F-FDG in prostate and small cell lung tumor bearing mice (3.7 MBq/mouse, iv). RESULTS: Radio-TLC and HPLC analyses of (18)F FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected). Cellular uptake of (18)F-FTP and (18)F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that (18)F FTP had less tumor uptake than (18)F-FDG in prostate cancer model. However, (18)F FTP had more uptake than (18)F-FDG in small cell lung cancer model. CONCLUSION: (18)F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by (18)F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response. PMID- 25136594 TI - Genetic testing in hereditary breast and ovarian cancer using massive parallel sequencing. AB - High throughput methods such as next generation sequencing are increasingly used in molecular diagnosis. The aim of this study was to develop a workflow for the detection of BRCA1 and BRCA2 mutations using massive parallel sequencing in a 454 GS Junior bench top sequencer. Our approach was first validated in a panel of 23 patients containing 62 unique variants that had been previously Sanger sequenced. Subsequently, 101 patients with familial breast and ovarian cancer were studied. BRCA1 and BRCA2 exon enrichment has been performed by PCR amplification using the BRCA MASTR kit (Multiplicom). Bioinformatic analysis of reads is performed with the AVA software v2.7 (Roche). In total, all 62 variants were detected resulting in a sensitivity of 100%. 71 false positives were called resulting in a specificity of 97.35%. All of them correspond to deletions located in homopolymeric stretches. The analysis of the homopolymers stretches of 6 bp or longer using the BRCA HP kit (Multiplicom) increased the specificity of the detection of BRCA1 and BRCA2 mutations to 99.99%. We show here that massive parallel pyrosequencing can be used as a diagnostic strategy to test for BRCA1 and BRCA2 mutations meeting very stringent sensitivity and specificity parameters replacing traditional Sanger sequencing with a lower cost. PMID- 25136595 TI - Effect of glass fiber incorporation on flexural properties of experimental composites. AB - This study evaluated the effect of fiber addiction in flexural properties of 30 wt% silica filled BisGMA resin (FR) or unfilled Bis-GMA (UR). Ten groups were created (N = 10) varying the resin (FR or UR) and quantity of glass fibers (wt%: 0, 10, 15, 20, and 30). Samples (10 * 2 * 1 mm) were submitted to flexural strength test following SEM examination. Data were analyzed by two-way ANOVA, Tukey, and Student t-test (alpha = 0.05). Results for flexural strength (MPa) were FR-groups: 0% (442.7 +/- 140.6)(C), 10% (772.8 +/- 446.3)(ABC), 15% (854.7 +/- 297.3)(AB), 20% (863.4 +/- 418.0)(A), 30% (459.5 +/- 140.5)(BC); UR-groups: 0% (187.7 +/- 120.3)(B), 10% (795.4 +/- 688.1)(B), 15% (1999.9 +/- 1258.6)(A), 20% (1911.5 +/- 596.8)(A), and 30% (2090.6 +/- 656.7)(A), and for flexural modulus (GPa) FR-groups: 0% (2065.63 +/- 882.15)(B), 10% (4479.06 +/- 3019.82)(AB), 15% (5694.89 +/- 2790.3)(A), 20% (6042.11 +/- 3392.13)(A), and 30% (2495.67 +/- 1345.86)(B); UR-groups: 0% (1090.08 +/- 708.81)(C), 10% (7032.13 +/- 7864.53)(BC), 15% (19331.57 +/- 16759.12)(AB), 20% (15726.03 +/- 8035.09)(AB), and 30% (29364.37 +/- 13928.96)(A). Fiber addiction in BisGMA resin increases flexural properties, and the interaction between resin and fibers seems better in the absence of inorganic fillers increasing flexural properties. PMID- 25136593 TI - Microenvironment, oncoantigens, and antitumor vaccination: lessons learned from BALB-neuT mice. AB - The tyrosine kinase human epidermal growth factor receptor 2 (HER2) gene is amplified in approximately 20% of human breast cancers and is associated with an aggressive clinical course and the early development of metastasis. Its crucial role in tumor growth and progression makes HER2 a prototypic oncoantigen, the targeting of which may be critical for the development of effective anticancer therapies. The setup of anti-HER2 targeting strategies has revolutionized the clinical outcome of HER2(+) breast cancer. However, their initial success has been overshadowed by the onset of pharmacological resistance that renders them ineffective. Since the tumor microenvironment (TME) plays a crucial role in drug resistance, the design of more effective anticancer therapies should depend on the targeting of both cancer cells and their TME as a whole. In this review, starting from the successful know-how obtained with a HER2(+) mouse model of mammary carcinogenesis, the BALB-neuT mice, we discuss the role of TME in mammary tumor development. Indeed, a deeper knowledge of antigens critical for cancer outbreak and progression and of the mechanisms that regulate the interplay between cancer and stromal cell populations could advise promising ways for the development of the best anticancer strategy. PMID- 25136597 TI - Management of the bleeding patient receiving new oral anticoagulants: a role for prothrombin complex concentrates. AB - Ease of dosing and simplicity of monitoring make new oral anticoagulants an attractive therapy in a growing range of clinical conditions. However, newer oral anticoagulants interact with the coagulation cascade in different ways than traditional warfarin therapy. Replacement of clotting factors will not reverse the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for these drugs are not widely available. Fortunately, withholding the anticoagulant and dialysis are freqnently effective treatments, particularly with rivaroxaban and dabigatran. Emergent bleeding, however, requires utilization of Prothrombin Complex Concentrates (PCCs). PCCs, in addition to recombinant factor VIIa, are used to activate the clotting system to reverse the effects of the new oral anticoagulants. In cases of refractory or emergent bleeding, the recommended factor concentrate in our protocols differs between the new oral anticoagulants. In patients taking dabigatran, we administer an activated PCC (aPCC) [FELBA] due to reported benefit in human in vitro studies. Based on human clinical trial evidence, the 4-factor PCC (Kcentra) is suggested for patients with refractory rivaroxaban- or apixaban-associated hemorrhage. If bleeding continues, recombinant factor VIIa may be employed. With all of these new procoagulant agents, the risk of thrombosis associated with administration of factor concentrates must be weighed against the relative risk of hemorrhage. PMID- 25136596 TI - Synergistic effects of toxic elements on heat shock proteins. AB - Heat shock proteins show remarkable variations in their expression levels under a variety of toxic conditions. A research span expanded over five decades has revealed their molecular characterization, gene regulation, expression patterns, vast similarity in diverse groups, and broad range of functional capabilities. Their functions include protection and tolerance against cytotoxic conditions through their molecular chaperoning activity, maintaining cytoskeleton stability, and assisting in cell signaling. However, their role as biomarkers for monitoring the environmental risk assessment is controversial due to a number of conflicting, validating, and nonvalidating reports. The current knowledge regarding the interpretation of HSPs expression levels has been discussed in the present review. The candidature of heat shock proteins as biomarkers of toxicity is thus far unreliable due to synergistic effects of toxicants and other environmental factors. The adoption of heat shock proteins as "suit of biomarkers in a set of organisms" requires further investigation. PMID- 25136598 TI - Hox transcription factors: modulators of cell-cell and cell-extracellular matrix adhesion. AB - Hox genes encode homeodomain-containing transcription factors that determine cell and tissue identities in the embryo during development. Hox genes are also expressed in various adult tissues and cancer cells. In Drosophila, expression of cell adhesion molecules, cadherins and integrins, is regulated by Hox proteins operating in hierarchical molecular pathways and plays a crucial role in segment specific organogenesis. A number of studies using mammalian cultured cells have revealed that cell adhesion molecules responsible for cell-cell and cell extracellular matrix interactions are downstream targets of Hox proteins. However, whether Hox transcription factors regulate expression of cell adhesion molecules during vertebrate development is still not fully understood. In this review, the potential roles Hox proteins play in cell adhesion and migration during vertebrate body patterning are discussed. PMID- 25136599 TI - Recombinant lysostaphin protects mice from methicillin-resistant Staphylococcus aureus pneumonia. AB - The advent of methicillin-resistant Staphylococcus aureus (MRSA) and the frequent and excessive abuse of ventilators have made MRSA pneumonia an inordinate threat to human health. Appropriate antibacterial therapies are crucial, including the use of lysostaphin as an alternative to antibiotics. To explore the potential use of lysostaphin as a therapeutic agent for MRSA pneumonia, mice were intranasally infected with MRSA and then treated with recombinant lysostaphin (rLys; 45 mg/kg in the high-dose group and 1 mg/kg in the low-dose group) (0.33 mg/mL, 15 mg/mL), vancomycin (120 mg/kg) (40 mg/mL), or phosphate-buffered saline (PBS, negative control) 4 h after infection. Therapeutic efficacy was assessed by mouse survival, lung histopathology, bacterial density in the lungs, bodyweight, lung weight, temperature, white blood cells counts, lymphocytes counts, granulocytes counts, and monocytes counts. The mice treated with rLys showed lower mortality, less lung parenchymal damage, and lower bacterial density at metastatic tissue sites than mice treated with PBS or vancomycin. The overall mortality was 100%, 60%, 40%, and 60% for the control, vancomycin, high-dose rLys, and low-dose rLys groups, respectively. These findings indicate that, as a therapeutic agent for MRSA pneumonia, lysostaphin exerts profound protective effects in mice against the morbidity and mortality associated with S. aureus pneumonia. PMID- 25136600 TI - Total bolus extraction method improves arterial image quality in dynamic CTAs derived from whole-brain CTP data. AB - Background and Purposes. The 320-detector row CT scanner enables visualization of whole-brain hemodynamic information (dynamic CT angiography (CTA) derived from CT perfusion scans). However, arterial image quality in dynamic CTA (dCTA) is inferior to arterial image quality in standard CTA. This study evaluates whether the arterial image quality can be improved by using a total bolus extraction (ToBE) method. Materials and Methods. DCTAs of 15 patients, who presented with signs of acute cerebral ischemia, were derived from 320-slice CT perfusion scans using both the standard subtraction method and the proposed ToBE method. Two neurointerventionalists blinded to the scan type scored the arterial image quality on a 5-point scale in the 4D dCTAs in consensus. Arteries were divided into four categories: (I) large extradural, (II) intradural (large, medium, and small), (III) communicating arteries, and (IV) cerebellar and ophthalmic arteries. Results. Quality of extradural and intradural arteries was significantly higher in the ToBE dCTAs than in the standard dCTAs (extradural P = 0.001, large intradural P < 0.001, medium intradural P < 0.001, and small intradural P < 0.001). Conclusion. The 4D dCTAs derived with the total bolus extraction (ToBE) method provide hemodynamic information combined with improved arterial image quality as compared to standard 4D dCTAs. PMID- 25136601 TI - Immune response, safety, and survival and quality of life outcomes for advanced colorectal cancer patients treated with dendritic cell vaccine and cytokine induced killer cell therapy. AB - PURPOSE: To determine the immune response after dendritic cell (DC) vaccine and cytokine-induced killer cells (CIK) therapy and assess its associated toxicity, survival benefit, and changes in the quality of life (QOL) of advanced colorectal cancer (CRC) patients. METHODS: We recruited 100 patients with unresectable CRC orrelapsed CRC after surgery who received DC vaccine and CIK cells (group immunotherapy, group I), and, as a control, 251 patients who had similar characteristics and underwent similar treatments, except for this immunotherapy (group nonimmunotherapy, group NI). After a follow-up period of 489.2 +/- 160.4 days, overall survival (OS) of the two groups was compared using the Kaplan-Meier method. RESULTS: In group I, 62% of patients developed a positive delayed type hypersensitivity response, and most patients showed an improvement in physical strength (75.2%), appetite (74.2%), sleeping (72.1%), and body weight (70.1%). Adverse events were fever (29.5%), insomnia (19.2%), anorexia (9.1%), sore joints (5.4%), and skin rash (1.0%). No toxicity was observed in patients treated with DC vaccine and CIK therapy. OS was significantly longer in group I than in group NI (P = 0.043). CONCLUSION: DC vaccine and CIK therapy were safe and could induce an immune response against CRC, thereby improving QOL and prolonging OS. PMID- 25136602 TI - Effect of cocoa butter and sunflower oil supplementation on performance, immunoglobulin, and antioxidant vitamin status of rats. AB - This study investigated the effects of cocoa butter and sunflower oil alone and in combination on performance, some biochemical parameters, immunoglobulin, and antioxidant vitamin status in Wistar rats. Forty-eight male rats were assigned to four groups, consisting of 12 rats with 3 replicates. Control received balanced rat diet without oil, cocoa butter group received 3.5% cocoa butter, sunflower oil group received 3.5% sunflower oil, the last group received 1.75% sunflower oil + 1.75% cocoa butter supplementation in the rat diet for 8 weeks. The total feed consumption in sunflower oil group was statistically lower than in the other groups. The serum creatinine level was decreased in cocoa butter group compared to control. Triglyceride and VLDL cholesterol levels were decreased in only sunflower oil and only cocoa butter groups as compared to control. The level of Ig M was statistically lower in cocoa butter and cocoa butter + sunflower oil groups than in control and sunflower oil groups. There were no statistically important difference in vitamin concentrations among trial groups. It was concluded that the supplementation of cocoa butter in diet decreased Ig M level, while the supplementation of cocoa butter and sunflower oil alone decreased the triglyceride and VLDL cholesterol levels. PMID- 25136603 TI - Anterior segment optical coherence tomography imaging of conjunctival filtering blebs after glaucoma surgery. AB - Time domain (TD) and spectral domain (SD) optical coherence tomography (OCT) are cross-sectional, noncontact, high-resolution diagnostic modalities for posterior and anterior segment (AS) imaging. The AS-OCT provides tomographic imaging of the cornea, iris, lens, and anterior chamber (AC) angle in several ophthalmic diseases. In glaucoma, AS-OCT is utilized to evaluate the morphology of AS structures involved in the pathogenesis of the disease, to obtain morphometric measures of the AC, to evaluate the suitability for laser or surgical approaches, and to assess modifications after treatment. In patients undergoing surgery, AS OCT is crucial in the evaluation of the filtering bleb functionality, permitting a combined qualitative and quantitative analysis. In this field, AS-OCT may help clinicians in distinguishing between functioning and nonfunctioning blebs by classifying their macroscopic morphology, describing bleb-wall features, bleb cavity, and scleral opening. This information is critical in recognizing signs of filtration failure earlier than the clinical approach and in planning the appropriate timing for management procedures in failing blebs. In this review, we summarize the applications of AS-OCT in the conjunctival bleb assessment. PMID- 25136605 TI - Computational analysis of the model describing HIV infection of CD4+T Cells. AB - An analysis of the model underpinning the description of the spread of HIV infection of CD4(+)T cells is examined in detail in this work. Investigations of the disease free and endemic equilibrium are done using the method of Jacobian matrix. An iteration technique, namely, the homotopy decomposition method (HDM), is implemented to give an approximate solution of nonlinear ordinary differential equation systems. The technique is described and illustrated with numerical examples. The approximated solution obtained via HDM is compared with those obtained via other methods to prove the trustworthiness of HDM. Moreover, the lessening and simplicity in calculations furnish HDM with a broader applicability. PMID- 25136604 TI - Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells. AB - High-risk human papillomavirus (HR-HPV) has been recognized as a major causative agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervical cancer cells. By using clustered regularly interspaced short palindromic repeats- (CRISPR-) associated protein system (CRISPR/Cas system), a widely used genome editing tool in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed for the first time that the HPV16-E7 single-guide RNA (sgRNA) guided CRISPR/Cas system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to downregulation of E7 protein and upregulation of tumor suppressor protein pRb. Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might be used as a therapeutic strategy for the treatment of cervical cancer. PMID- 25136606 TI - Inference of SNP-gene regulatory networks by integrating gene expressions and genetic perturbations. AB - In order to elucidate the overall relationships between gene expressions and genetic perturbations, we propose a network inference method to infer gene regulatory network where single nucleotide polymorphism (SNP) is involved as a regulator of genes. In the most of the network inferences named as SNP-gene regulatory network (SGRN) inference, pairs of SNP-gene are given by separately performing expression quantitative trait loci (eQTL) mappings. In this paper, we propose a SGRN inference method without predefined eQTL information assuming a gene is regulated by a single SNP at most. To evaluate the performance, the proposed method was applied to random data generated from synthetic networks and parameters. There are three main contributions. First, the proposed method provides both the gene regulatory inference and the eQTL identification. Second, the experimental results demonstrated that integration of multiple methods can produce competitive performances. Lastly, the proposed method was also applied to psychiatric disorder data in order to explore how the method works with real data. PMID- 25136607 TI - Clinical applications of end-to-side neurorrhaphy: an update. AB - End-to-side neurorrhaphy constitutes an interesting option to regain nerve function after damage in selected cases, in which conventional techniques are not feasible. In the last twenty years, many experimental and clinical studies have been conducted in order to understand the biological mechanisms and to test the effectiveness of this technique, with contrasting results. In this updated review, we consider the state of the art about end-to-side coaptation, focusing on all the current clinical applications, such as sensory and mixed nerve repair, treatment of facial palsy, and brachial plexus injuries and painful neuromas management. PMID- 25136608 TI - Ruscogenin ameliorates experimental nonalcoholic steatohepatitis via suppressing lipogenesis and inflammatory pathway. AB - The aim of the study was to investigate the protective effects of ruscogenin, a major steroid sapogenin in Ophiopogon japonicus, on experimental models of nonalcoholic steatohepatitis. HepG2 cells were exposed to 300 MUmol/l palmitic acid (PA) for 24 h with the preincubation of ruscogenin for another 24 h. Ruscogenin (10.0 MUmol/l) had inhibitory effects on PA-induced triglyceride accumulation and inflammatory markers in HepG2 cells. Male golden hamsters were randomly divided into five groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) by gavage once daily for 8 weeks. Ruscogenin alleviated dyslipidemia, liver steatosis, and necroinflammation and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. Hepatic mRNA levels involved in fatty acid oxidation were increased in ruscogenin-treated HFD-fed hamsters. Conversely, ruscogenin decreased expression of genes involved in hepatic lipogenesis. Gene expression of inflammatory cytokines, chemoattractive mediator, nuclear transcription factor-(NF-) kappaB, and alpha-smooth muscle actin were increased in the HFD group, which were attenuated by ruscogenin. Ruscogenin may attenuate HFD-induced steatohepatitis through downregulation of NF-kappaB-mediated inflammatory responses, reducing hepatic lipogenic gene expression, and upregulating proteins in beta-oxidation pathway. PMID- 25136609 TI - IOL power calculation after corneal refractive surgery. AB - PURPOSE: To describe the different formulas that try to overcome the problem of calculating the intraocular lens (IOL) power in patients that underwent corneal refractive surgery (CRS). METHODS: A Pubmed literature search review of all published articles, on keyword associated with IOL power calculation and corneal refractive surgery, as well as the reference lists of retrieved articles, was performed. RESULTS: A total of 33 peer reviewed articles dealing with methods that try to overcome the problem of calculating the IOL power in patients that underwent CRS were found. According to the information needed to try to overcome this problem, the methods were divided in two main categories: 18 methods were based on the knowledge of the patient clinical history and 15 methods that do not require such knowledge. The first group was further divided into five subgroups based on the parameters needed to make such calculation. CONCLUSION: In the light of our findings, to avoid postoperative nasty surprises, we suggest using only those methods that have shown good results in a large number of patients, possibly by averaging the results obtained with these methods. PMID- 25136610 TI - Blood vessel-derived acellular matrix for vascular graft application. AB - To overcome the issues connected to the use of autologous vascular grafts and artificial materials for reconstruction of small diameter (<6 mm) blood vessels, this study aimed to develop acellular matrix- (AM-) based vascular grafts. Rat iliac arteries were decellularized by a detergent-enzymatic treatment, whereas endothelial cells (ECs) were obtained through enzymatic digestion of rat skin followed by immunomagnetic separation of CD31-positive cells. Sixteen female Lewis rats (8 weeks old) received only AM or previously in vitro reendothelialized AM as abdominal aorta interposition grafts (about 1 cm). The detergent-enzymatic treatment completely removed the cellular part of vessels and both MHC class I and class II antigens. One month after surgery, the luminal surface of implanted AMs was partially covered by ECs and several platelets adhered in the areas lacking cell coverage. Intimal hyperplasia, already detected after 1 month, increased at 3 months. On the contrary, all grafts composed by AM and ECs were completely covered at 1 month and their structure was similar to that of native vessels at 3 months. Taken together, our findings show that prostheses composed of AM preseeded with ECs could be a promising approach for the replacement of blood vessels. PMID- 25136612 TI - Efficient expression of acetylcholine-binding protein from Aplysia californica in Bac-to-Bac system. AB - The Bac-to-Bac baculovirus expression system can efficiently produce recombinant proteins, but the system may have to be optimized to achieve high-level expression for different candidate proteins. We reported here the efficient expression of acetylcholine-binding proteins from sea hares Aplysia californica (Ac-AChBP) and a convenient method to monitor protein expression level in this expression system. Three key factors affecting expression of Ac-AChBP were optimized for maximizing the yield, which included the cell density, volume of the infecting baculovirus inoculums, and the culturing time of postinfection. We have found it to reach a high yield of ~5 mg/L, which needs 55 h incubation after infection at the cell density of 2 * 10(6) cells/mL with an inoculum volume ratio of 1 : 100. The optimized expression system in this study was also applied for expressing another protein Ls-AChBP from Lymnaea stagnalis successfully. Therefore, this established method is helpful to produce high yields of AChBP proteins for X-ray crystallographic structural and functional studies. PMID- 25136611 TI - Alternative splicing generates different parkin protein isoforms: evidences in human, rat, and mouse brain. AB - Parkinson protein 2, E3 ubiquitin protein ligase (PARK2) gene mutations are the most frequent causes of autosomal recessive early onset Parkinson's disease and juvenile Parkinson disease. Parkin deficiency has also been linked to other human pathologies, for example, sporadic Parkinson disease, Alzheimer disease, autism, and cancer. PARK2 primary transcript undergoes an extensive alternative splicing, which enhances transcriptomic diversification. To date several PARK2 splice variants have been identified; however, the expression and distribution of parkin isoforms have not been deeply investigated yet. Here, the currently known PARK2 gene transcripts and relative predicted encoded proteins in human, rat, and mouse are reviewed. By analyzing the literature, we highlight the existing data showing the presence of multiple parkin isoforms in the brain. Their expression emerges from conflicting results regarding the electrophoretic mobility of the protein, but it is also assumed from discrepant observations on the cellular and tissue distribution of parkin. Although the characterization of each predicted isoforms is complex, since they often diverge only for few amino acids, analysis of their expression patterns in the brain might account for the different pathogenetic effects linked to PARK2 gene mutations. PMID- 25136613 TI - Does platelet-rich plasma freeze-thawing influence growth factor release and their effects on chondrocytes and synoviocytes? AB - PRP cryopreservation remains a controversial point. Our purpose was to investigate the effect of freezing/thawing on PRP molecule release, and its effects on the metabolism of chondrocytes and synoviocytes. PRP was prepared from 10 volunteers, and a half volume underwent one freezing/thawing cycle. IL-1beta, HGF, PDGF AB/BB, TGF-beta1, and VEGF were assayed 1 hour and 7 days after activation. Culture media of chondrocytes and synoviocytes were supplemented with fresh or frozen PRP, and, at 7 days, proliferation, gene expression, and secreted proteins levels were evaluated. Results showed that in the freeze-thawed PRP the immediate and delayed molecule releases were similar or slightly lower than those in fresh PRP. TGF-beta1 and PDGF AB/BB concentrations were significantly reduced after freezing both at 1 hour and at 7 days, whereas HGF concentration was significantly lower in frozen PRP at 7 days. In fresh PRP IL-1beta and HGF concentrations underwent a significant further increase after 7 days. Similar gene expression was found in chondrocytes cultured with both PRPs, whereas in synoviocytes HGF gene expression was higher in frozen PRP. PRP cryopreservation is a safe procedure, which sufficiently preserves PRP quality and its ability to induce proliferation and the production of ECM components in chondrocytes and synoviocytes. PMID- 25136614 TI - Intensive insulin therapy for septic patients: a meta-analysis of randomized controlled trials. AB - Background. Studies on the effect of intensive insulin therapy (IIT) in septic patients with hyperglycemia have given inconsistent results. The primary purpose of this meta-analysis was to evaluate whether it is effective in reducing mortality. Methods. We searched PubMed, Embase, the Cochrane Library, clinicaltrials.gov, and relevant reference lists up to September 2013 and including randomized controlled trials that compared IIT with conventional glucose management in septic patients. Study quality was assessed using the Cochrane Risk of Bias Tool. And our primary outcome measure was pooled in the random effects model. Results. We identified twelve randomized controlled trials involving 4100 patients. Meta-analysis showed that IIT did not reduce any of the outcomes: overall mortality (risk ratio [RR] = 0.98, 95% CI [0.85, 1.15], P = 0.84), 28-day mortality (RR = 0.66, 95% CI [0.40, 1.10], P = 0.11), 90-day mortality (RR = 1.10, 95% CI [0.97, 1.26], P = 0.13), ICU mortality (RR = 0.94, 95% CI [0.77, 1.14], P = 0.52), hospital mortality (RR = 0.98, 95% CI [0.86, 1.11], P = 0.71), severity of illness, and length of ICU stay. Conversely, the incidence of hypoglycemia was markedly higher in the IIT (RR = 2.93, 95% CI [1.69, 5.06], P = 0.0001). Conclusions. For patients with sepsis, IIT and conservative glucose management show similar efficacy, but ITT is associated with a higher incidence of hypoglycemia. PMID- 25136615 TI - Human endogenous retrovirus W activity in cartilage of osteoarthritis patients. AB - The etiology of viruses in osteoarthritis remains controversial because the prevalence of viral nucleic acid sequences in peripheral blood or synovial fluid from osteoarthritis patients and that in healthy control subjects are similar. Until now the presence of virus has not been analyzed in cartilage. We screened cartilage and chondrocytes from advanced and non-/early osteoarthritis patients for parvovirus B19, herpes simplex virus-1, Epstein Barr virus, cytomegalovirus, human herpes virus-6, hepatitis C virus, and human endogenous retroviruses transcripts. Endogenous retroviruses transcripts, but none of the other viruses, were detected in 15 out the 17 patients. Sequencing identified the virus as HERV WE1 and E2. HERV-W activity was confirmed by high expression levels of syncytin, dsRNA, virus budding, and the presence of virus-like particles in all advanced osteoarthritis cartilages examined. Low levels of HERV-WE1, but not E2 envelope RNA, were observed in 3 out of 8 non-/early osteoarthritis patients, while only 3 out of 7 chondrocytes cultures displayed low levels of syncytin, and just one was positive for virus-like particles. This study demonstrates for the first time activation of HERV-W in cartilage of osteoarthritis patients; however, a causative role for HERV-W in development or deterioration of the disease remains to be proven. PMID- 25136616 TI - Description of a novel adhesin of Mycobacterium avium subsp. paratuberculosis. AB - The binding and ingestion of Mycobacterium avium subsp. paratuberculosis (MAP) by host cells are fibronectin (FN) dependent. In several species of mycobacteria, a specific family of proteins allows the attachment and internalization of these bacteria by epithelial cells through interaction with FN. Thus, the identification of adhesion molecules is essential to understand the pathogenesis of MAP. The aim of this study was to identify and characterize FN binding cell wall proteins of MAP. We searched for conserved adhesins within a large panel of surface immunogenic proteins of MAP and investigated a possible interaction with FN. For this purpose, a cell wall protein fraction was obtained and resolved by 2D electrophoresis. The immunoreactive spots were identified by MALDI-TOF MS and a homology search was performed. We selected elongation factor Tu (EF-Tu) as candidate for further studies. We demonstrated the FN-binding capability of EF-Tu using a ligand blot assay and also confirmed the interaction with FN in a dose dependent manner by ELISA. The dissociation constant of EF-Tu was determined by surface plasmon resonance and displayed values within the MUM range. These data support the hypothesis that this protein could be involved in the interaction of MAP with epithelial cells through FN binding. PMID- 25136617 TI - Chemical composition, leishmanicidal and cytotoxic activities of the essential oils from Mangifera indica L. var. Rosa and Espada. AB - The essential oils from Mangifera indica var. Rosa and Espada latex were obtained by hydrodistillation and analyzed using GC-FID and GC-MS. Twenty-seven components were identified. The main compound in the essential oil from M. indica var. Espada (EOMiE) was terpinolene (73.6%). The essential oil of M. indica var. Rosa (EOMiR) was characterized by high amounts of beta-pinene (40.7%) and terpinolene (28.3%). In the test for leishmanicidal activity against promastigotes forms of L. amazonensis, EOMiR and EOMiE showed IC50 (72 h) of 39.1 and 23.0 MUg/mL, respectively. In macrophages, EOMiR and EOMiE showed CC50 of 142.84 and 158.65 MUg/mL, respectively. However, both were more specific to the parasite than macrophages, with values of selectivity index of 6.91 for EOMiE and 3.66 for EOMiR. The essential oils were evaluated for their cytotoxicity against the human tumor cells HEp-2, HT-29, NCI-H292, and HL-60. The EOMiR and EOMiE were most effective against the HL-60, with IC50 values of 12.3 and 3.6 MUg/mL, respectively. The results demonstrated that the essential oils of M. indica can destroy L. amazonensis and inhibit tumor cell growth. These findings contribute to the knowledge of the Brazilian biodiversity as a source of potential therapeutic agents. PMID- 25136618 TI - The prognostic and risk-stratified value of heart-type fatty-acid-binding protein in community acquired pneumonia in emergency department. AB - OBJECTIVE: To evaluate the prognostic and risk stratified ability of heart-type fatty-acid-binding protein (H-FABP) in patients with community acquired pneumonia (CAP) in emergency department (ED) and to compare it with Pneumonia Severity Index (PSI) and CURB-65. METHODS: Consecutive adult CAP patients admitted to the ED of Beijing Chao-Yang Hospital were enrolled. Circulating H-FABP and troponin I were measured. PSI and CURB-65 were calculated in all patients. The differences in 28-day mortality and requirement for mechanical ventilation (MV) or a vasopressor within 6 h after ED arrival were compared in patients with positive H FABP (>=7 ng/mL) and negative ones (<7 ng/mL). Receiver operating characteristic (ROC) curve and logistic regression were used to assess the predictive value of H FABP. RESULTS: From August to November 2012, 229 CAP patients were enrolled. The 28-day mortality, PSI, CURB-65, and incidence of using MV or a vasopressor were much higher in H-FABP-positive patients than in negative ones (P < 0.01). H-FABP was an independent predictor of the 28-day mortality. The area under the ROC curve (AUC) of H-FABP was 0.751. Combination of H-FABP and CURB-65 (AUC = 0.824) or H-FABP and PSI (AUC = 0.820) improved their prognostic performance. CONCLUSIONS: H-FABP was valuable for prognosis and risk stratification in CAP patients in ED. PMID- 25136619 TI - Comparison of reaction response time between hand and foot controlled devices in simulated microsurgical testing. AB - PURPOSE: We hypothesized that reaction times (RTs) for a switch release are faster for hand-controlled than for foot-controlled switches for physiological and anatomical reasons (e.g., nerve conduction speed). The risk of accidental trauma could be reduced if the surgeon reacted quicker and therefore improve the surgical outcome. METHOD: We included 47 medical professionals at USC. Demographics and handedness were recorded. Under a microscope, a simple reaction time test was performed, testing all extremities multiple times in a random order. Additionally, a subjective questionnaire was administered. RESULTS: The mean RTs for hands are 318.24 ms +/- 51.13 and feet 328.69 +/- 48.70. The comparison of hand versus foot showed significant shorter RTs for the hand (P = 0.025). Partially significant differences between and within the experience level groups could be demonstrated by level of education (LE) and microscopic surgeries/week (MSW) (P = 0.57-0.02). In the subjective questionnaire, 91.5% (n = 43/47) of test subjects prefer to use hand controls. CONCLUSION: Our data show that the RT for hands is faster than feet. Similarly the subjective questionnaire showed a greater preference for hand actuation. This data suggest a hand controlled ophthalmic instrument might have distinct advantages; however, clinical correlation is required. PMID- 25136620 TI - Epidemiology, phylogeny, and evolution of emerging enteric Picobirnaviruses of animal origin and their relationship to human strains. AB - Picobirnavirus (PBV) which has been included in the list of viruses causing enteric infection in animals is highly versatile because of its broad host range and genetic diversity. PBVs are among the most recent and emerging small, nonenveloped viruses with a bisegmented double-stranded RNA genome, classified under a new family "Picobirnaviridae." PBVs have also been detected from respiratory tract of pigs, but needs further close investigation for their inhabitant behavior. Though, accretion of genomic data of PBVs from different mammalian species resolved some of the ambiguity, quite a few questions and hypotheses regarding pathogenesis, persistence location, and evolution of PBVs remain unreciprocated. Evolutionary analysis reveals association of PBVs with partitiviruses especially fungi partitiviruses. Although, PBVs may have an ambiguous clinical implication, they do pose a potential public health concern in humans and control of PBVs mainly relies on nonvaccinal approach. Based upon the published data, from 1988 to date, generated from animal PBVs across the globe, this review provides information and discussion with respect to genetic analysis as well as evolution of PBVs of animal origin in relation to human strains. PMID- 25136621 TI - Obligatory role for endothelial heparan sulphate proteoglycans and caveolae internalization in catestatin-dependent eNOS activation. AB - The chromogranin-A peptide catestatin modulates a wide range of processes, such as cardiovascular functions, innate immunity, inflammation, and metabolism. We recently found that the cardiac antiadrenergic action of catestatin requires a PI3K-dependent NO release from endothelial cells, although the receptor involved is yet to be identified. In the present work, based on the cationic properties of catestatin, we tested the hypothesis of its interaction with membrane heparan sulphate proteoglycans, resulting in the activation of a caveolae-dependent endocytosis. Experiments were performed on bovine aortic endothelial cells. Endocytotic vesicles trafficking was quantified by confocal microscopy using a water-soluble membrane dye; catestatin colocalization with heparan sulphate proteoglycans and caveolin 1 internalization were studied by fluorimetric measurements in live cells. Modulation of the catestatin-dependent eNOS activation was assessed by immunofluorescence and immunoblot analysis. Our results demonstrate that catestatin (5 nM) colocalizes with heparan sulphate proteoglycans and induces a remarkable increase in the caveolae-dependent endocytosis and caveolin 1 internalization, which were significantly reduced by both heparinase and wortmannin. Moreover, catestatin was unable to induce Ser(1179) eNOS phosphorylation after pretreatments with heparinase and methyl beta-cyclodextrin. Taken together, these results highlight the obligatory role for proteoglycans and caveolae internalization in the catestatin-dependent eNOS activation in endothelial cells. PMID- 25136622 TI - Preclinical and clinical effects of mistletoe against breast cancer. AB - Breast cancer is among the most frequent types of cancer in women worldwide. Current conventional treatment options are accompanied by side effects. Mistletoe is amongst the important herbal medicines traditionally used as complementary remedies. An increasing number of studies have reported anticancer activity of mistletoe extracts on breast cancer cells and animal models. Some recent evidence suggests that cytotoxic activity of mistletoe may be mediated through different mechanisms. These findings provide a good base for clinical trials. Various studies on mistletoe therapy for breast cancer patients revealed similar findings concerning possible benefits on survival time, health-related quality of life (HRQoL), remission rate, and alleviating adverse reactions to conventional therapy. This review provides an overview of the recent findings on preclinical experiments and clinical trials of mistletoe for its cytotoxic and antitumor activity and its effect on HRQoL in breast cancer patients. Moreover, studies investigating molecular and cellular mechanisms underlying antitumor activity of mistletoe are discussed in this paper. The analyzed trials provided evidence that there might be a combination of pharmacological and motivational aspects mediated by the mistletoe extract application which may contribute to the clinical benefit and positive outcome such as improved HRQoL and self-regulation in breast cancer patients. PMID- 25136624 TI - Modified titanium implant as a gateway to the human body: the implant mediated drug delivery system. AB - The aim of this study was to investigate the efficacy of a proposed new implant mediated drug delivery system (IMDDS) in rabbits. The drug delivery system is applied through a modified titanium implant that is configured to be implanted into bone. The implant is hollow and has multiple microholes that can continuously deliver therapeutic agents into the systematic body. To examine the efficacy and feasibility of the IMDDS, we investigated the pharmacokinetic behavior of dexamethasone in plasma after a single dose was delivered via the modified implant placed in the rabbit tibia. After measuring the plasma concentration, the areas under the curve showed that the IMDDS provided a sustained release for a relatively long period. The result suggests that the IMDDS can deliver a sustained release of certain drug components with a high bioavailability. Accordingly, the IMDDS may provide the basis for a novel approach to treating patients with chronic diseases. PMID- 25136625 TI - The type of fat ingested at breakfast influences the plasma lipid profile of postmenopausal women. AB - To assess whether the type of fat ingested at breakfast can modify the plasma lipid profile and other cardiovascular risk variables in postmenopausal women at risk of cardiovascular disease, a longitudinal, randomized, and crossover study was carried out with postmenopausal women at risk of CVD. They were randomly assigned to eat each type of breakfast during one month: 6 study periods (breakfast with the same composition plus butter/margarine/virgin olive oil) separated by two washout periods. On the first and last days of each study period, weight, arterial blood pressure, heart rate, and body mass index were recorded in fasting conditions and a blood sample was collected to measure plasma lipid profile. When comparing final values to baseline values, we only found out statistically significant differences on plasma lipid profiles. Butter-based breakfast increased total cholesterol and HDL, while margarine-based breakfast decreased total cholesterol and LDL and increased HDL. After the olive oil-based breakfast intake, a tendency towards a decrease of total cholesterol and LDL levels and an increase of HDL levels was observed. No statistically significant differences were observed in triglycerides levels, BMI, and arterial pressure in any breakfast type. The margarine-based breakfast was the only one which significantly increased the percentage of volunteers with optimal lipid profiles. The polyunsaturated fat at breakfast has improved the plasma lipid profile in the analyzed sample population, suggesting that PUFA-based breakfast can be advisable in women at risk of CVD. PMID- 25136623 TI - BRCA-associated ovarian cancer: from molecular genetics to risk management. AB - Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA mutation in OC patients has been suggested as a prognostic and predictive factor. In addition, the identification of asymptomatic carriers of such mutations offers an unprecedented opportunity for OC prevention. This review is aimed at exploring the current knowledge on epidemiological and molecular aspects of BRCA-associated OC predisposition, on pathology and clinical behavior of OC occurring in BRCA mutation carriers, and on the available options for managing asymptomatic carriers. PMID- 25136626 TI - Fermentative polyhydroxybutyrate production from a novel feedstock derived from bakery waste. AB - In this study, Halomonas boliviensis was cultivated on bakery waste hydrolysate and seawater in batch and fed-batch cultures for polyhydroxybutyrate (PHB) production. Results demonstrated that bakery waste hydrolysate and seawater could be efficiently utilized by Halomonas boliviensis while PHB contents between 10 and 30% (w/w) were obtained. Furthermore, three methods for bakery waste hydrolysis were investigated for feedstock preparation. These include: (1) use of crude enzyme extracts from Aspergillus awamori, (2) Aspergillus awamori solid mashes, and (3) commercial glucoamylase. In the first method, the resultant free amino nitrogen (FAN) concentration in hydrolysates was 150 and 250 mg L(-1) after 20 hours at enzyme-to-solid ratios of 6.9 and 13.1 U g(-1), respectively. In both cases, the final glucose concentration was around 130-150 g L(-1). In the second method, the resultant FAN and glucose concentrations were 250 mg L(-1) and 150 g L(-1), respectively. In the third method, highest glucose and lowest FAN concentrations of 170-200 g L(-1) and 100 mg L(-1), respectively, were obtained in hydrolysates after only 5 hours. The present work has generated promising information contributing to the sustainable production of bioplastic using bakery waste hydrolysate. PMID- 25136627 TI - Abarema cochliacarpos extract decreases the inflammatory process and skeletal muscle injury induced by Bothrops leucurus venom. AB - Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation. PMID- 25136629 TI - Hot-stage microscopy for determination of API particles in a formulated tablet. AB - Although methods exist to readily determine the particle size distribution (PSD) of an active pharmaceutical ingredient (API) before its formulation into a final product, the primary challenge is to develop a method to determine the PSD of APIs in a finished tablet. To address the limitations of existing PSD methods, we used hot-stage microscopy to observe tablet disintegration during temperature change and, thus, reveal the API particles in a tablet. Both mechanical and liquid disintegration were evaluated after we had identified optimum milling time for mechanical disintegration and optimum volume of water for liquid disintegration. In each case, hot-stage micrographs, taken before and after the API melting point, were compared with image analysis software to obtain the PSDs. Then, the PSDs of the APIs from the disintegrated tablets were compared with the PSDs of raw APIs. Good agreement was obtained, thereby confirming the robustness of our methodology. The availability of such a method equips pharmaceutical scientists with an in vitro assessment method that will more reliably determine the PSD of active substances in finished tablets. PMID- 25136628 TI - Evaluation of the efficacy of 50% autologous serum eye drops in different ocular surface pathologies. AB - PURPOSE: This study evaluated the efficacy of 50% autologous serum eye drops in ocular surface diseases not improved by conventional therapy. METHODS: We analyzed two groups: (1) acute eye pathologies (e.g., chemical burns) and (2) chronic eye pathologies (e.g., recurrent corneal erosion, neurotropic keratitis, and keratoconjunctivitis sicca). The patients were treated for surface instability after conventional therapy. The patients received therapy 5 times a day until stabilization of the framework; they then reduced therapy to 3 times a day for at least 3 months. We analyzed the best corrected visual acuity, epithelial defects, inflammation, corneal opacity, and corneal neovascularization. We also analyzed symptoms such as tearing, burning, sense of foreign body or sand, photophobia, blurred vision, and difficulty opening the eyelids. RESULTS: We enrolled 15 eyes in group 1 and 11 eyes in group 2. The average therapy period was 16 +/- 5.86 weeks in group 1 and 30.54 +/- 20.33 weeks in group 2. The epithelial defects all resolved. Signs and symptoms improved in both groups. In group 2, the defect recurred after the suspension of therapy in 2 (18%) patients; in group 1, no defects recurred. CONCLUSIONS: Autologous serum eye drops effectively stabilize and improve signs and symptoms in eyes previously treated with conventional therapy. PMID- 25136631 TI - Large-scale genomic analysis of codon usage in dengue virus and evaluation of its phylogenetic dependence. AB - The increasing number of dengue virus (DENV) genome sequences available allows identifying the contributing factors to DENV evolution. In the present study, the codon usage in serotypes 1-4 (DENV1-4) has been explored for 3047 sequenced genomes using different statistics methods. The correlation analysis of total GC content (GC) with GC content at the three nucleotide positions of codons (GC1, GC2, and GC3) as well as the effective number of codons (ENC, ENCp) versus GC3 plots revealed mutational bias and purifying selection pressures as the major forces influencing the codon usage, but with distinct pressure on specific nucleotide position in the codon. The correspondence analysis (CA) and clustering analysis on relative synonymous codon usage (RSCU) within each serotype showed similar clustering patterns to the phylogenetic analysis of nucleotide sequences for DENV1-4. These clustering patterns are strongly related to the virus geographic origin. The phylogenetic dependence analysis also suggests that stabilizing selection acts on the codon usage bias. Our analysis of a large scale reveals new feature on DENV genomic evolution. PMID- 25136632 TI - Anatomic changes in the macroscopic morphology and microarchitecture of denervated long bone tissue after spinal cord injury in rats. AB - To study the effects of mechanical loading on bones after SCI, we assessed macro- and microscopic anatomy in rats submitted to passive standing (PS) and electrical stimulation (ES). The study design was based on two main groups of juvenile male Wistar rats with SCI: one was followed for 33 days with therapies starting at day 3 and the other was followed for 63 days with therapies starting at day 33. Both groups were composed of four subgroups (n = 10/group): (1) Sham, (2) SCI, (3) SCI + PS, and (4) SCI + ES. Rehabilitation protocol consisted of a 20-minute session, 3x/wk for 30 days. The animals were sequentially weighed and euthanized. The femur and tibia were assessed macroscopically and microscopically by scanning electronic microscopy (SEM). The SCI rats gained less weight than Sham-operated animals. Significant reduction of bone mass and periosteal radii was observed in the SCI rats, whereas PS and ES efficiently improved the macroscopic parameters. The SEM images showed less and thin trabecular bone in SCI rats. PS and ES efficiently ameliorated the bone microarchitecture deterioration by thickening and increasing the trabeculae. Based on the detrimental changes in bone tissue following SCI, the mechanical loading through weight bearing and muscle contraction may decrease the bone loss and restore the macro- and microanatomy. PMID- 25136630 TI - Potential therapeutic strategies for Alzheimer's disease targeting or beyond beta amyloid: insights from clinical trials. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder with two hallmarks: beta-amyloid plagues and neurofibrillary tangles. It is one of the most alarming illnesses to elderly people. No effective drugs and therapies have been developed, while mechanism-based explorations of therapeutic approaches have been intensively investigated. Outcomes of clinical trials suggested several pitfalls in the choice of biomarkers, development of drug candidates, and interaction of drug-targeted molecules; however, they also aroused concerns on the potential deficiency in our understanding of pathogenesis of AD, and ultimately stimulated the advent of novel drug targets tests. The anticipated increase of AD patients in next few decades makes development of better therapy an urgent issue. Here we attempt to summarize and compare putative therapeutic strategies that have completed clinical trials or are currently being tested from various perspectives to provide insights for treatments of Alzheimer's disease. PMID- 25136633 TI - Acute in vivo response to an alternative implant for urogynecology. AB - PURPOSE: To investigate in vivo the acute host response to an alternative implant designed for the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). METHODS: A biodegradable scaffold was produced from poly-L-lactic acid (PLA) using the electrospinning technique. Human and rat adipose-derived stem cells (ADSCs) were isolated and characterized by fluorescence-activated cell sorting and differentiation assays. PLA scaffolds were seeded and cultured for 2 weeks with human or rat ADSCs. Scaffolds with and without human or rat ADSCs were implanted subcutaneously on the abdominal wall of rats. After 3 and 7 days, 6 animals from each group were sacrificed. Sections from each sample were analyzed by Haematoxylin and Eosin staining, Sirius red staining, and immunohistochemistry for CD68, PECAM-1, and collagen I and III. RESULTS: Animals responded to the scaffolds with an acute macrophage response. After 7 days of implantation, there was extensive host cell penetration, new blood vessel formation, and new collagen deposition throughout the full thickness of the samples without obvious differences between cell-containing and cell-free scaffolds. CONCLUSIONS: The acute in vivo response to an alternative implant (both with and without cells) for the treatment of SUI and POP showed good acute integration into the host tissues. PMID- 25136635 TI - Pathological feature and immunoprofile of cystitis glandularis accompanied with upper urinary tract obstruction. AB - OBJECTIVE: To explore the pathological feature and immunoprofile of immunoprofile accompanied with upper urinary tract obstruction and the immunoprofile in various types of glandular cystitis. METHODS: Pathological sections from 31 cases of cystitis glandularis with upper urinary tract obstruction and 34 cases of cystitis glandularis without upper urinary tract obstruction were observed as pathological feature on microscopy. Meanwhile, an immunohistochemical analysis was employed to determine the expression of p53, Ki67, p21, MMP-9, MUC1, MUC2, and COX-2. RESULTS: In the two groups, main pathological type was transitional epithelial, followed by intestinal epithelial; other types were a few, and the difference between the two groups was not significant. All immunohistochemical expressions of p53, Ki67, p21, MMP-9, MUC1, MUC2, and COX-2 were positive in varying degrees, and there was no significant difference between the groups. Transitional epithelial type was compared with mixed type; the difference of COX 2 was significant, P < 0.05. The differences of immunohistochemical expression among other different pathologic types were not significant. CONCLUSIONS: It is suggested that glandular cystitis accompanied with upper urinary tract obstruction shares the same pathological feature and immunoprofile as that without upper urinary tract obstruction. No significant differences of immunohistochemical expression in tissue are in cystitis glandularis with different pathological types. PMID- 25136636 TI - Potential smoothened inhibitor from traditional Chinese medicine against the disease of diabetes, obesity, and cancer. AB - Nowadays, obesity becomes a serious global problem, which can induce a series of diseases such as type 2 diabetes mellitus, cancer, cardiovascular disease, metabolic syndrome, and stoke. For the mechanisms of diseases, the hedgehog signaling pathway plays an important role in body patterning during embryogenesis. For this reason, smoothened homologue (Smo) protein had been indicated as the drug target. In addition, the small-molecule Smo inhibitor had also been used in oncology clinical trials. To improve drug development of TCM compounds, we aim to investigate the potent lead compounds as Smo inhibitor from the TCM compounds in TCM Database@Taiwan. The top three TCM compounds, precatorine, labiatic acid, and 2,2'-[benzene-1,4-diylbis(methanediyloxybenzene 4,1-diyl)]bis(oxoacetic acid), have displayed higher potent binding affinities than the positive control, LY2940680, in the docking simulation. After MD simulations, which can optimize the result of docking simulation and validate the stability of H-bonds between each ligand and Smo protein under dynamic conditions, top three TCM compounds maintain most of interactions with Smo protein, which keep the ligand binding stable in the binding domain. Hence, we propose precatorine, labiatic acid, and 2,2'-[benzene-1,4 diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid) as potential lead compounds for further study in drug development process with the Smo protein. PMID- 25136637 TI - Dracocephalum: novel anticancer plant acting on liver cancer cell mitochondria. AB - Dracocephalum kotschyi Boiss. (Labiatae) is a native Iranian medicinal plant which has been used in combination with Peganum harmala L. as a remedy for many forms of human cancer especially leukemia and gastrointestinal malignancies. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In this investigation HCC was induced by a single intraperitoneal injection of diethylnitrosamine (DEN) in corn oil at 200 mg/kg body weight to rats. Two weeks after DEN administration, cancer development was promoted with dietary 2-acetylaminofluorene (2-AAF) (0.02%, w/w) for 2 weeks. Serum alpha fetoprotein (AFP) concentration, serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) activities were also determined for confirmation of hepatocellular carcinoma induction. Then rat hepatocytes were isolated with collagen perfusion technique and tumoral hepatocytes were sorted by flow cytometry. Finally isolated mitochondria obtained from both tumoral and nontumoral hepatocytes were used for any probable toxic effect of Dracocephalum kotschyi ethanolic extract. Our results showed that D. kotschyi extract (250 ug/mL) induced reactive oxygen species (ROS) formation, mitochondrial membrane permeabilization (MMP), and mitochondrial swelling and cytochrome c release only in tumoral but not nontumoral hepatocyte. These findings propose Dracocephalum kotschyi as a promising candidate for future anticancer research. PMID- 25136638 TI - The effects of vitamin E and omega-3 PUFAs on endothelial function among adolescents with metabolic syndrome. AB - AIM: The present study aims to explore the effects of vitamin E and omega-3 on endothelial function indicators among adolescents with metabolic syndrome. METHOD: In a randomized, double blind, and placebo-controlled trial, 90 young individuals, aged 10 to 18 years, with metabolic syndrome were randomly assigned to receive either vitamin E tablets (400 IU/day) or omega-3 tablets (2.4 gr/day) or placebo. For assessing endothelial functional state, the serum level of vascular endothelial growth factor (VEGF) was measured by ELISA test. RESULTS: The use of omega-3 supplementation for eight weeks led to significant increase in serum HDL level compared with the group treated with vitamin E or placebo group. In this regard, no significant correlations were found between the change in VEGF and baseline levels of other markers including anthropometric indices and serum lipids. Omega-3 could significantly reduce VEGF with the presence of other baseline variables (Beta = -12.55; P = 0.012). CONCLUSION: The administration of omega-3 can effectively improve endothelial function in adolescents with metabolic syndrome by reducing the level of serum VEGF, as a major index for atherosclerosis progression and endothelial destabilization. Omega-3 can be proposed as a VEGF antagonist for improving endothelial function in metabolic syndrome. The clinical implications of our findings should be assessed in future studies. PMID- 25136639 TI - Magnetic resonance imaging for the normal mesostenium and involvement of the mesostenium in acute pancreatitis. AB - The main point of this paper is to study MRI findings of the normal mesostenium and the involvement of the mesostenium in acute pancreatitis and to discuss the relationship between the involvement of the mesostenium and the severity of acute pancreatitis. In clinical practice, the mesenterical involvement in acute pancreatitis was often observed on MRI in daily works, which was little recorded in the reported studies. We conducted the current study to assess the mesenterical involvement in acute pancreatitis with MRI. We found that the mesenterical involvement of acute pancreatitis patients is common on MRI. The mesenterical involvement has a positive correlation with the MR severity index and the Acute Physiology and Chronic Healthy Evaluation II scoring system. It has been shown that MR can be used to visualize mesenterical involvement, which is a supplementary indicator in evaluating the severity of acute pancreatitis and local and systemic complications. PMID- 25136634 TI - Drug delivery systems, CNS protection, and the blood brain barrier. AB - Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID- 25136640 TI - Murine aortic smooth muscle cells acquire, though fail to present exogenous protein antigens on major histocompatibility complex class II molecules. AB - In the present study aortic murine smooth muscle cell (SMC) antigen presentation capacity was evaluated using the Ealpha-GFP/Y-Ae system to visualize antigen uptake through a GFP tag and tracking of Ealpha peptide/MHCII presentation using the Y-Ae Ab. Stimulation with IFN-gamma (100 ng/mL) for 72 h caused a significant (P < 0.01) increase in the percentage of MHC class II positive SMCs, compared with unstimulated cells. Treatment with Ealpha-GFP (100 MUg/mL) for 48 h induced a significant (P < 0.05) increase in the percentage of GFP positive SMCs while it did not affect the percentage of Y-Ae positive cells, being indicative of antigen uptake without its presentation in the context of MHC class II. After IFN-gamma stimulation, ovalbumin- (OVA, 1 mg/mL) or OVA323-339 peptide-(0.5 MUg/mL) treated SMCs failed to induce OT-II CD4(+) T cell activation/proliferation; this was also accompanied by a lack of expression of key costimulatory molecules (OX40L, CD40, CD70, and CD86) on SMCs. Finally, OVA-treated SMCs failed to induce DO11.10-GFP hybridoma activation, a process independent of costimulation. Our results demonstrate that while murine primary aortic SMCs express MHC class II and can acquire exogenous antigens, they fail to activate T cells through a failure in antigen presentation and a lack of costimulatory molecule expression. PMID- 25136642 TI - Diabetic retinopathy treated with laser photocoagulation and the indirect effect on glycaemic control. AB - PURPOSE: To identify any possible relation between glycaemic control and previous laser photocoagulation for diabetic retinopathy. METHODS: Seventy-two patients with diabetes were included in the study and were separated into 2 groups according to previous treatment (group A) or not (group B) with argon laser photocoagulation. Glycaemic control was estimated by measuring blood levels of HbA1c in four consecutive measurements. RESULTS: Blood levels of HbA1c in group A were significantly lower 3, 6, and 12 months after laser treatment as compared to blood levels of HbA1c before laser treatment (7.1 +/- 0.4% versus 7.6 +/- 0.9%, 7.2 +/- 0.2% versus 7.6 +/- 0.9%, and 7.1 +/- 0.2% versus 7.6 +/- 0.9%, resp., all P < 0.05). Blood levels of HbA1c in group B did not differ significantly in four consecutive measurements. CONCLUSION: Our results suggest that we should anticipate a better glycaemic control in cases of patients with diabetes previously treated with laser photocoagulation. PMID- 25136641 TI - Protein kinase D3 is essential for prostratin-activated transcription of integrated HIV-1 provirus promoter via NF-kappaB signaling pathway. AB - Prostratin has been proposed as a promising reagent for eradicating the latent HIV-1 provirus by inducing HIV-1 transcription activation. The molecular mechanism of this activation, however, is far from clear. Here, we show that the protein kinase D3 (PKD3) is essential for prostratin-induced transcription activation of latent HIV-1 provirus. First, silencing PKD3, but not the other members of PKD family, blocked prostratin-induced transcription of HIV-1. Second, overexpressing the constitutively active form of PKD3, but not the wild-type or kinase-dead form of PKD3, augmented the expression of HIV-1. Consistent with this observation, we found that prostratin could trigger PKD3 activation by inducing the phosphorylation of its activation loop. In addition, we identified PKCepsilon of the novel PKC subfamily as the upstream kinase for this phosphorylation. Finally, the activation effect of PKD3 on HIV-1 transcription was shown to depend on the presence of kappaB element and the prostratin-induced activation of NF kappaB, as indicated by the fact that silencing PKD3 blocked prostratin-induced NF-kappaB activation and NF-kappaB-dependent HIV-1 transcription. Therefore, for the first time, PKD3 is implicated in the transcription activation of latent HIV 1 provirus, and our results revealed a molecular mechanism of prostratin-induced HIV-1 transcription via PKCepsilon/PKD3/NF-kappaB signaling pathway. PMID- 25136643 TI - Real life cancer comorbidity in Greek patients with diabetes mellitus followed up at a single diabetes center: an unappreciated new diabetes complication. AB - We determined cancer comorbidity in patients with diabetes followed up at a single Greek academic clinic and investigated the potential related factors. Cancer comorbidity was prospectively recorded for all patients with type 2 (T2DM, n = 759) or type 1 (T1DM, n = 134) diabetes of at least 10-year duration examined during one year. Patient characteristics, diabetes age of onset, duration, treatment, control, and complication rates were compared between subjects with and without cancer. Moreover, a retrospective collection of data from similar patients examined for the first time during the last 25 years, but lost to follow up, after at least one-year's regular visits, was performed. In regularly followed-up T2DM patients cancer comorbidity was 12.6%. Patients with cancer were older and more frequently smokers. Prostate cancer was the most frequent (24.0%) type. In T1DM cancer comorbidity was 3.0%. Similar rates of comorbidity and types of cancer were observed in lost to follow-up patients. In conclusion, our patients with T2DM of at least 10-year' duration show high cancer comorbidity. No specific characteristics discriminate patients with cancer. Therefore presymptomatic cancer detection and prevention strategies may have to be incorporated into the annual systematic evaluation of our patients. PMID- 25136644 TI - Rectal sensitivity in diabetes patients with symptoms of gastroparesis. AB - In a clinical setting, diabetic autonomic complications (cardiac, gastrointestinal, urogenital, etc.) are often handled as separate entities. We investigated rectal sensitivity to heat, mechanical distension, and electrical stimulations in 20 patients with diabetes and symptoms of gastroparesis, to evaluate the extent of visceral neuronal damage. Furthermore, to evaluate the relation between the nervous structures we examined gastric emptying and cardiac autonomic function with the hypothesis being an association between these. We found that 60% of patients had delayed gastric empting. Rectal hyposensitivity was a general finding as they tolerated 67% higher thermal, 42% more mechanical, and 33% higher electrical current intensity compared to healthy controls. In patients, most heart rate variability parameters were reduced; they reported significantly more gastrointestinal symptoms and a reduced quality of life in all SF-36 domains. Shortened RR interval correlated with reduced rectal temperature sensitivity, and gastric retention rate was negatively associated with symptoms of nausea and vomiting. To conclude, in these patients with signs and symptoms of diabetic gastroparesis, rectal sensitivity was reduced, and heart rate variability was impaired. Thus, we suggest regarding diabetic autonomic neuropathy as a diffuse disorder. Symptoms of widespread autonomic dysfunction and sensory disorders should be expected and treated in these patients. PMID- 25136645 TI - The effect of diabetes self-management education on body weight, glycemic control, and other metabolic markers in patients with type 2 diabetes mellitus. AB - AIMS: To comprehensively evaluate the effect of a short-term diabetes self management education (DSME) on metabolic markers and atherosclerotic parameters in patients with type 2 diabetes. METHODS: 76 patients with type 2 diabetes were recruited in this study. They were divided into the intervention group (n = 36) and control group (n = 40). The patients in the intervention group received a 3 month intervention, including an 8-week education on self-management of diabetes mellitus and subsequent 4 weeks of practice of the self-management guidelines. The patients in the control group received standard advice on medical nutrition therapy. Metabolic markers, carotid intima-media thickness (CIMT), and carotid arterial stiffness (CAS) of the patients in both groups were assessed before and after the 3-month intervention. RESULTS: There was a significant reduction in hemoglobin A1c (HbA1c, -0.2 +/- 0.56% versus 0.08 +/- 0.741%; P < 0.05) and body weight (-1.19 +/- 1.39 kg versus -0.61 +/- 2.04 kg; P < 0.05) in the intervention group as compared to the control group. However, no significant improvements were found in other metabolic markers, CIMT and CAS (P > 0.05). CONCLUSIONS: DSME can improve HbA1c and body weight in patients with type 2 diabetes. PMID- 25136647 TI - Pollution characteristics and possible sources of seldom monitored trace elements in surface sediments collected from Three Gorges Reservoir, China. AB - A geochemical study of Three Gorges Reservoir (TGR) sediments was carried out to analyze the concentrations, distribution, accumulation, and potential sources of the seldom monitored trace elements (SMTEs). The mean concentrations of Li, B, Be, Bi, V, Co, Ga, Sn, Sb, and Tl were 47.08, 2.47, 59.15, 0.50, 119.20, 17.83, 30.31, 3.25, 4.14, and 0.58 mg/kg, respectively. The concentrations of total SMTEs, together with their spatial distribution, showed that the SMTEs were mainly due to anthropogenic inputs in the region of TGR. The assessment by Geoaccumulation Index indicates that Tl, Be, V, Co, and Fe are at the unpolluted level; Bi, Li, Ga, and Sn were at the "uncontaminated to moderately contaminated" level. However, B was classified as "moderately contaminated" level and Sb was ranked as "strongly contaminated" level. The pollution level of the SMTEs is Sb > B > Bi > Li > Ga > Sn > Tl > Be > V > Co > Fe. The results of Correlation Analysis and Principal Component Analysis indicated Be, V, Co, Ga, Sn, Tl, Bi, and Fe in sediments have a natural source. B and Li were positively correlated with each other and mainly attributed into similar anthropogenic input. In addition, Sb has less relationship with other SMTEs, indicating that Sb has another kind of anthropogenic source. PMID- 25136646 TI - Effects of pristane alone or combined with chloroquine on macrophage activation, oxidative stress, and TH1/TH2 skewness. AB - We investigated the protective role of chloroquine against pristane-induced macrophage activation, oxidative stress, and Th1/Th2 skewness in C57BL/6J mice. Those mice were treated with pristane alone or combined with chloroquine. Hematological and biochemical parameters, macrophage phagocytic function, the oxidant/antioxidant index, cytokine for IFN-gamma, TNF-alpha, IL-4, and IL-6, and the isotypes of IgG2a and IgG1 were determined. And the expression of T-bet/GATA 3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR. We found that pristane treatment for a period of 12 or 24 weeks triggered macrophage activation syndrome, characterized by hemophagocytosis in spleen and peripheral blood, enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and leucopenia, increased anti-Smith, lactic dehydrogenase, triglyceride, and ferritin, as well as hypercytokinemia of IFN-gamma, TNF-alpha, IL-4, and IL-6. In parallel, a significant increase in lipid peroxidation and a decrease in superoxide dismutase, glutathione, and catalase activity, as well as a skewed Th1/Th2 balance in spleen, were observed. However, chloroquine supplementation showed a remarkable amelioration of these abnormalities. Our data indicate that pristane administration induces macrophage activation, oxidative stress, and Th1/Th2 skewness, which can be attenuated by chloroquine. PMID- 25136648 TI - Low-cost dielectric substrate for designing low profile multiband monopole microstrip antenna. AB - This paper proposes a small sized, low-cost multiband monopole antenna which can cover the WiMAX bands and C-band. The proposed antenna of 20 * 20 mm(2) radiating patch is printed on cost effective 1.6 mm thick fiberglass polymer resin dielectric material substrate and fed by 4 mm long microstrip line. The finite element method based, full wave electromagnetic simulator HFSS is efficiently utilized for designing and analyzing the proposed antenna and the antenna parameters are measured in a standard far-field anechoic chamber. The experimental results show that the prototype of the antenna has achieved operating bandwidths (voltage stand wave ratio (VSWR) less than 2) 360 MHz (2.53 2.89 GHz) and 440 MHz (3.47-3.91 GHz) for WiMAX and 1550 MHz (6.28-7.83 GHz) for C-band. The simulated and measured results for VSWR, radiation patterns, and gain are well matched. Nearly omnidirectional radiation patterns are achieved and the peak gains are of 3.62 dBi, 3.67 dBi, and 5.7 dBi at 2.66 GHz, 3.65 GHz, and 6.58 GHz, respectively. PMID- 25136649 TI - A routing path construction method for key dissemination messages in sensor networks. AB - Authentication is an important security mechanism for detecting forged messages in a sensor network. Each cluster head (CH) in dynamic key distribution schemes forwards a key dissemination message that contains encrypted authentication keys within its cluster to next-hop nodes for the purpose of authentication. The forwarding path of the key dissemination message strongly affects the number of nodes to which the authentication keys in the message are actually distributed. We propose a routing method for the key dissemination messages to increase the number of nodes that obtain the authentication keys. In the proposed method, each node selects next-hop nodes to which the key dissemination message will be forwarded based on secret key indexes, the distance to the sink node, and the energy consumption of its neighbor nodes. The experimental results show that the proposed method can increase by 50-70% the number of nodes to which authentication keys in each cluster are distributed compared to geographic and energy-aware routing (GEAR). In addition, the proposed method can detect false reports earlier by using the distributed authentication keys, and it consumes less energy than GEAR when the false traffic ratio (FTR) is >= 10%. PMID- 25136650 TI - Graph-based symbolic technique and its application in the frequency response bound analysis of analog integrated circuits. AB - A new graph-based symbolic technique (GBST) for deriving exact analytical expressions like the transfer function H(s) of an analog integrated circuit (IC), is introduced herein. The derived H(s) of a given analog IC is used to compute the frequency response bounds (maximum and minimum) associated to the magnitude and phase of H(s), subject to some ranges of process variational parameters, and by performing nonlinear constrained optimization. Our simulations demonstrate the usefulness of the new GBST for deriving the exact symbolic expression for H(s), and the last section highlights the good agreement between the frequency response bounds computed by our variational analysis approach versus traditional Monte Carlo simulations. As a conclusion, performing variational analysis using our proposed GBST for computing the frequency response bounds of analog ICs, shows a gain in computing time of 100x for a differential circuit topology and 50x for a 3-stage amplifier, compared to traditional Monte Carlo simulations. PMID- 25136651 TI - An action-based fine-grained access control mechanism for structured documents and its application. AB - This paper presents an action-based fine-grained access control mechanism for structured documents. Firstly, we define a describing model for structured documents and analyze the application scenarios. The describing model could support the permission management on chapters, pages, sections, words, and pictures of structured documents. Secondly, based on the action-based access control (ABAC) model, we propose a fine-grained control protocol for structured documents by introducing temporal state and environmental state. The protocol covering different stages from document creation, to permission specification and usage control are given by using the Z-notation. Finally, we give the implementation of our mechanism and make the comparisons between the existing methods and our mechanism. The result shows that our mechanism could provide the better solution of fine-grained access control for structured documents in complicated networks. Moreover, it is more flexible and practical. PMID- 25136652 TI - Determination of the sediment carrying capacity based on perturbed theory. AB - According to the previous studies of sediment carrying capacity, a new method of sediment carrying capacity on perturbed theory was proposed. By taking into account the average water depth, average flow velocity, settling velocity, and other influencing factors and introducing the median grain size as one main influencing factor in deriving the new formula, we established a new sediment carrying capacity formula. The coefficients were determined by the principle of dimensional analysis, multiple linear regression method, and the least square method. After that, the new formula was verified through measuring data of natural rivers and flume tests and comparing the verified results calculated by Cao Formula, Zhang Formula, Li Formula, Engelung-Hansen Formula, Ackers-White Formula, and Yang Formula. According to the compared results, it can be seen that the new method is of high accuracy. It could be a useful reference for the determination of sediment carrying capacity. PMID- 25136653 TI - Multivariable time series prediction for the icing process on overhead power transmission line. AB - The design of monitoring and predictive alarm systems is necessary for successful overhead power transmission line icing. Given the characteristics of complexity, nonlinearity, and fitfulness in the line icing process, a model based on a multivariable time series is presented here to predict the icing load of a transmission line. In this model, the time effects of micrometeorology parameters for the icing process have been analyzed. The phase-space reconstruction theory and machine learning method were then applied to establish the prediction model, which fully utilized the history of multivariable time series data in local monitoring systems to represent the mapping relationship between icing load and micrometeorology factors. Relevant to the characteristic of fitfulness in line icing, the simulations were carried out during the same icing process or different process to test the model's prediction precision and robustness. According to the simulation results for the Tao-Luo-Xiong Transmission Line, this model demonstrates a good accuracy of prediction in different process, if the prediction length is less than two hours, and would be helpful for power grid departments when deciding to take action in advance to address potential icing disasters. PMID- 25136654 TI - Inducing effect of dihydroartemisinic acid in the biosynthesis of artemisinins with cultured cells of Artemisia annua by enhancing the expression of genes. AB - Artemisinin has been used in the production of "artemisinin combination therapies" for the treatment of malaria. Feeding of precursors has been proven to be one of the most effective methods to enhance artemisinin production in plant cultured cells. At the current paper, the biosynthesis of artemisinin (ART) and its four analogs from dihydroartemisinic acid (DHAA) in suspension-cultured cells of Artemisia annua were investigated. ARTs were detected by HPLC/GC-MS and isolated by various chromatography methods. The structures of four DHAA metabolites, namely, dihydro-epi-deoxyarteannuin B, arteannuin I, arteannuin K, and 3-beta-hydroxy-dihydro-epi-deoxyarteannuin B, were elucidated by physicochemical and spectroscopic analyses. The correlation between gene expression and ART content was investigated. The results of RT-PCR showed that DHAA could up-regulate expression of amorpha-4,11-diene synthase gene (ADS), amorpha-4,11-diene C-12 oxidase gene (CYP71AV1), and farnesyl diphosphate synthase gene (FPS) (3.19-, 7.21-, and 2.04-fold higher than those of control group, resp.), which indicated that biosynthesis processes from DHAA to ART were enzyme-mediated. PMID- 25136655 TI - Automatic foreground extraction based on difference of Gaussian. AB - A novel algorithm for automatic foreground extraction based on difference of Gaussian (DoG) is presented. In our algorithm, DoG is employed to find the candidate keypoints of an input image in different color layers. Then, a keypoints filter algorithm is proposed to get the keypoints by removing the pseudo-keypoints and rebuilding the important keypoints. Finally, Normalized cut (Ncut) is used to segment an image into several regions and locate the foreground with the number of keypoints in each region. Experiments on the given image data set demonstrate the effectiveness of our algorithm. PMID- 25136656 TI - Comprehensive Aspectual UML approach to support AspectJ. AB - Unified Modeling Language is the most popular and widely used Object-Oriented modelling language in the IT industry. This study focuses on investigating the ability to expand UML to some extent to model crosscutting concerns (Aspects) to support AspectJ. Through a comprehensive literature review, we identify and extensively examine all the available Aspect-Oriented UML modelling approaches and find that the existing Aspect-Oriented Design Modelling approaches using UML cannot be considered to provide a framework for a comprehensive Aspectual UML modelling approach and also that there is a lack of adequate Aspect-Oriented tool support. This study also proposes a set of Aspectual UML semantic rules and attempts to generate AspectJ pseudocode from UML diagrams. The proposed Aspectual UML modelling approach is formally evaluated using a focus group to test six hypotheses regarding performance; a "good design" criteria-based evaluation to assess the quality of the design; and an AspectJ-based evaluation as a reference measurement-based evaluation. The results of the focus group evaluation confirm all the hypotheses put forward regarding the proposed approach. The proposed approach provides a comprehensive set of Aspectual UML structural and behavioral diagrams, which are designed and implemented based on a comprehensive and detailed set of AspectJ programming constructs. PMID- 25136657 TI - Radixin enhances colon cancer cell invasion by increasing MMP-7 production via Rac1-ERK pathway. AB - As a member of the ezrin-radixin-moesin (ERM) family, radixin is overexpressed in many tumor tissues. However, little is known about its role in the progression of colon cancer. So we here aimed to determine the function of radixin in colon cancer cell invasion. Interestingly, we found that the expression of radixin was significantly elevated in colon cancer cells. Knockdown of radixin suppressed the invasion and migration of colon cancer cells. Further, knockdown of radixin inhibited the activation of Rac1 and ERK1/2, and decreased the expression and secretion of MMP-7. In addition, Rac1-ERK signaling pathway was required for the radixin-promoted invasion and MMP-7 production. Together, our findings suggest that radixin enhances the invasion and migration of colon cancer cells. Activation of Rac1-ERK pathway and consequent upregulation of MMP-7 production may contribute to the function of radixin in the regulation of colon cancer cell invasion. Thus, radixin may act as a novel target for the diagnosis and treatment of colon cancer. PMID- 25136659 TI - Advanced approach to information security management system model for industrial control system. AB - Organizations make use of important information in day-to-day business. Protecting sensitive information is imperative and must be managed. Companies in many parts of the world protect sensitive information using the international standard known as the information security management system (ISMS). ISO 27000 series is the international standard ISMS used to protect confidentiality, integrity, and availability of sensitive information. While an ISMS based on ISO 27000 series has no particular flaws for general information systems, it is unfit to manage sensitive information for industrial control systems (ICSs) because the first priority of industrial control is safety of the system. Therefore, a new information security management system based on confidentiality, integrity, and availability as well as safety is required for ICSs. This new ISMS must be mutually exclusive of an ICS. This paper provides a new paradigm of ISMS for ICSs, which will be shown to be more suitable than the existing ISMS. PMID- 25136658 TI - The role of IL-33 in host response to Candida albicans. AB - BACKGROUND: Interleukin (IL) 33 is a recently identified pleiotropic cytokine that influences the activity of multiple cell types and orchestrates complex innate and adaptive immune responses. METHODS: We performed an extensive review of the literature published between 2005 and 2013 on IL-33 and related cytokines, their functions, and their regulation of the immune system following Candida albicans colonization. Our literature review included cross-references from retrieved articles and specific data from our own studies. RESULTS: IL-33 (IL 1F11) is a recently identified member of the IL-1 family of cytokines. Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host immune defense against fungal pathogens, including C. albicans. IL-33 induces a Th2-type inflammatory response and activates both innate and adaptive immunity. Studies in animal models have shown that Th2 inflammatory responses have a beneficial role in immunity against gastrointestinal and systemic infections by Candida spp. CONCLUSIONS: This review summarizes the most important clinical studies and case reports describing the beneficial role of IL-33 in immunity and host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2 axis is involved in therapeutic target has implications for the prevention and treatment of inflammatory diseases, including acute or chronic candidiasis. PMID- 25136660 TI - Induced effects of transcranial magnetic stimulation on the autonomic nervous system and the cardiac rhythm. AB - Several standard protocols based on repetitive transcranial magnetic stimulation (rTMS) have been employed for treatment of a variety of neurological disorders. Despite their advantages in patients that are retractable to medication, there is a lack of knowledge about the effects of rTMS on the autonomic nervous system that controls the cardiovascular system. Current understanding suggests that the shape of the so-called QRS complex together with the size of the different segments and intervals between the PQRST deflections of the heart could predict the nature of the different arrhythmias and ailments affecting the heart. This preliminary study involving 10 normal subjects from 20 to 30 years of age demonstrated that rTMS can induce changes in the heart rhythm. The autonomic activity that controls the cardiac rhythm was indeed altered by an rTMS session targeting the motor cortex using intensity below the subject's motor threshold and lasting no more than 5 minutes. The rTMS activation resulted in a reduction of the RR intervals (cardioacceleration) in most cases. Most of these cases also showed significant changes in the Poincare plot descriptor SD2 (long-term variability), the area under the low frequency (LF) power spectrum density curve, and the low frequency to high frequency (LF/HF) ratio. The RR intervals changed significantly in specific instants of time during rTMS activation showing either heart rate acceleration or heart rate deceleration. PMID- 25136661 TI - An improved Pearson's correlation proximity-based hierarchical clustering for mining biological association between genes. AB - Microarray gene expression datasets has concerned great awareness among molecular biologist, statisticians, and computer scientists. Data mining that extracts the hidden and usual information from datasets fails to identify the most significant biological associations between genes. A search made with heuristic for standard biological process measures only the gene expression level, threshold, and response time. Heuristic search identifies and mines the best biological solution, but the association process was not efficiently addressed. To monitor higher rate of expression levels between genes, a hierarchical clustering model was proposed, where the biological association between genes is measured simultaneously using proximity measure of improved Pearson's correlation (PCPHC). Additionally, the Seed Augment algorithm adopts average linkage methods on rows and columns in order to expand a seed PCPHC model into a maximal global PCPHC (GL PCPHC) model and to identify association between the clusters. Moreover, a GL PCPHC applies pattern growing method to mine the PCPHC patterns. Compared to existing gene expression analysis, the PCPHC model achieves better performance. Experimental evaluations are conducted for GL-PCPHC model with standard benchmark gene expression datasets extracted from UCI repository and GenBank database in terms of execution time, size of pattern, significance level, biological association efficiency, and pattern quality. PMID- 25136662 TI - The design and implementation of postprocessing for depth map on real-time extraction system. AB - Depth estimation becomes the key technology to resolve the communications of the stereo vision. We can get the real-time depth map based on hardware, which cannot implement complicated algorithm as software, because there are some restrictions in the hardware structure. Eventually, some wrong stereo matching will inevitably exist in the process of depth estimation by hardware, such as FPGA. In order to solve the problem a postprocessing function is designed in this paper. After matching cost unique test, the both left-right and right-left consistency check solutions are implemented, respectively; then, the cavities in depth maps can be filled by right depth values on the basis of right-left consistency check solution. The results in the experiments have shown that the depth map extraction and postprocessing function can be implemented in real time in the same system; what is more, the quality of the depth maps is satisfactory. PMID- 25136663 TI - Realistic facial expression of virtual human based on color, sweat, and tears effects. AB - Generating extreme appearances such as scared awaiting sweating while happy fit for tears (cry) and blushing (anger and happiness) is the key issue in achieving the high quality facial animation. The effects of sweat, tears, and colors are integrated into a single animation model to create realistic facial expressions of 3D avatar. The physical properties of muscles, emotions, or the fluid properties with sweating and tears initiators are incorporated. The action units (AUs) of facial action coding system are merged with autonomous AUs to create expressions including sadness, anger with blushing, happiness with blushing, and fear. Fluid effects such as sweat and tears are simulated using the particle system and smoothed-particle hydrodynamics (SPH) methods which are combined with facial animation technique to produce complex facial expressions. The effects of oxygenation of the facial skin color appearance are measured using the pulse oximeter system and the 3D skin analyzer. The result shows that virtual human facial expression is enhanced by mimicking actual sweating and tears simulations for all extreme expressions. The proposed method has contribution towards the development of facial animation industry and game as well as computer graphics. PMID- 25136664 TI - Hematite nanoparticles-modified electrode based electrochemical sensing platform for dopamine. AB - Hematite (alpha-Fe2O3) nanoparticles were synthesized by the solid transformation of ferrous hydroxide and ferrihydrite in hydrothermal condition. The as-prepared alpha-Fe2O3 nanoparticles were characterized by UV-vis, PL, XRD, Raman, TEM, AFM, FESEM, and EDX analysis. The experimental results indicated the formation of uniform hematite nanoparticles with an average size of 45 nm and perfect crystallinity. The electrochemical behavior of a GC/alpha-Fe2O3 electrode was studied using CV and EIS techniques with an electrochemical probe, [Fe(CN)6](3-/4 ) redox couple. The electrocatalytic activity was investigated toward DA oxidation in a phosphate buffer solution (pH 6.8) by varying different experimental parameters. The chronoamperometric study showed a linear response in the range of 0-2 MUM with LoD of 1.6 MUM for DA. Square wave voltammetry showed a linear response in the range of 0-35 MUM with LoD of 236 nM for DA. PMID- 25136665 TI - Kinetics of mushroom tyrosinase and melanogenesis inhibition by N-acetyl pentapeptides. AB - We investigated the kinetics of 4N-acetyl-pentapeptides, Ac-P1, Ac-P2, Ac-P3, and Ac-P4, regarding inhibition of mushroom tyrosinase activity. The peptides sequences of Ac-P1, Ac-P2, Ac-P3, and Ac-P4 were Ac-RSRFK, Ac-KSRFR, Ac-KSSFR, and Ac-RSRFS, respectively. The 4N-acetyl-pentapeptides were able to reduce the oxidation of l-DOPA by tyrosinase in a dose-dependent manner. Of the 4N-acetyl pentapeptides, only Ac-P4 exhibited lag time (80 s) at a concentration of 0.5 mg/mL. The tyrosinase inhibitory effects of Ac-P4 (IC50 0.29 mg/mL) were more effective than those of Ac-P1, Ac-P2, and Ac-P3, in which IC50s were 0.75 mg/mL, 0.78 mg/mL, and 0.81 mg/mL, respectively. Kinetic analysis demonstrated that all 4N-acetyl-pentapeptides were mixed-type tyrosinase inhibitors. Furthermore, 0.1 mg/mL of Ac-P4 exhibited significant melanogenesis inhibition on B16F10 melanoma cells and was more effective than kojic acid. The melanogenesis inhibition of Ac P4 was dose-dependent and did not induce any cytotoxicity on B16F10 melanoma cells. PMID- 25136667 TI - Optimization of self-directed target coverage in wireless multimedia sensor network. AB - Video and image sensors in wireless multimedia sensor networks (WMSNs) have directed view and limited sensing angle. So the methods to solve target coverage problem for traditional sensor networks, which use circle sensing model, are not suitable for WMSNs. Based on the FoV (field of view) sensing model and FoV disk model proposed, how expected multimedia sensor covers the target is defined by the deflection angle between target and the sensor's current orientation and the distance between target and the sensor. Then target coverage optimization algorithms based on expected coverage value are presented for single-sensor single-target, multisensor single-target, and single-sensor multitargets problems distinguishingly. Selecting the orientation that sensor rotated to cover every target falling in the FoV disk of that sensor for candidate orientations and using genetic algorithm to multisensor multitargets problem, which has NP complete complexity, then result in the approximated minimum subset of sensors which covers all the targets in networks. Simulation results show the algorithm's performance and the effect of number of targets on the resulting subset. PMID- 25136666 TI - Turbulence model sensitivity and scour gap effect of unsteady flow around pipe: a CFD study. AB - A numerical investigation of incompressible and transient flow around circular pipe has been carried out at different five gap phases. Flow equations such as Navier-Stokes and continuity equations have been solved using finite volume method. Unsteady horizontal velocity and kinetic energy square root profiles are plotted using different turbulence models and their sensitivity is checked against published experimental results. Flow parameters such as horizontal velocity under pipe, pressure coefficient, wall shear stress, drag coefficient, and lift coefficient are studied and presented graphically to investigate the flow behavior around an immovable pipe and scoured bed. PMID- 25136670 TI - Knee joint biomechanics in high flexion. PMID- 25136669 TI - Micropropagation of an exotic ornamental plant, Calathea crotalifera, for production of high quality plantlets. AB - A successful protocol was established for micropropagation in two selected varieties of exotic ornamental plants, Calathea crotalifera. The effects of different sterilization techniques, explant type, and the combination and concentration of plant growth regulators on shoots induction were studied. The axillary shoot buds explants sprouted from rhizomes in soil free conditions showed high induction rate of shoots with lowest contamination percentage when treated with combination of 30% (v/v) NaOCl, 70% (v/v) ethanol, and 0.3% (w/v) HgCl2. In the present study, the highest number of multiple shoots was obtained in MS basal medium supplemented with 3.5 mg/L 6-Benzylaminopurine (BAP), 1.0 mg/L 1-Naphthaleneacetic acid (NAA), 3% sucrose, and 6 g/L plant agar for both varieties and was used as multiplication medium. Microshoots were highly induced when the young shoot bud explants were incised longitudinally prior subculture. Chlorophyll analysis was studied to test the effects of activated charcoal and L glutamine on reduction of necrosis problem. The maximum roots induction was recorded on MS medium supplemented with 1.0 mg/L 1-Naphthaleneacetic acid (NAA) compared to indolebutyric acid (IBA). The complete regenerated plantlets were successfully acclimatized in the soilless medium under greenhouse condition. This is the first report of rapid mass propagation for C. crotalifera. PMID- 25136668 TI - Neoadjuvant chemotherapy with FOLFOX4 regimen to treat advanced gastric cancer improves survival without increasing adverse events: a retrospective cohort study from a Chinese center. AB - BACKGROUND/AIM: To evaluate the clinical efficacy of FOLFOX4 (5 fluomumcil/leucovorin combined and oxaliplatin) neoadjuvant chemotherapy for advanced gastric cancer (AGC). PATIENTS AND METHODS: Fifty-eight AGC patients were enrolled in this retrospective cohort study, 23 in the neoadjuvant group and 35 in the adjuvant group. R0 resection, survival, and adverse events were compared. RESULTS: The two groups were well-matched, with no significant differences in R0 resection rate (82.6% versus 82.0%) and number of lymph nodes dissection (16 (0-49) versus 13 (3-40)) between the two groups (P > 0.05). The number of lymph node metastases in the neoadjuvant group (3 (0-14)) was significantly fewer than that in the adjuvant group (6 (0-27)) (P = 0.04). The neoadjuvant group had significantly better median overall survival (29.0 versus 22.0 months) and 3-year survival rate (73.9% versus 40.0%) than the adjuvant group (P = 0.013). The positive expression rate of Ki-67 in the neoadjuvant group (40.0%, 8/20) was lower than that in the adjuvant group (74.2%, 23/31; P = 0.015). CONCLUSION: The FOLFOX4 neoadjuvant chemotherapy could improve survival without increasing adverse events in patients with AGC. PMID- 25136671 TI - The role of antioxidant enzymes in adaptive responses to sheath blight infestation under different fertilization rates and hill densities. AB - Sheath blight of rice, caused by Rhizoctonia solani, is one of the most devastating rice diseases worldwide. No rice cultivar has been found to be completely resistant to this fungus. Identifying antioxidant enzymes activities (activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)) and malondialdehyde content (MDA) responding to sheath blight infestation is imperative to understand the defensive mechanism systems of rice. In the present study, two inoculation methods (toothpick and agar block method) were tested in double-season rice. Toothpick method had greater lesion length than agar block method in late season. A higher MDA content was found under toothpick method compared with agar block method, which led to greater POD and SOD activities. Dense planting caused higher lesion length resulting in a higher MDA content, which also subsequently stimulated higher POD and SOD activity. Sheath blight severity was significantly related to the activity of antioxidant enzyme during both seasons. The present study implies that rice plants possess a system of antioxidant protective enzymes which helps them in adaptation to sheath blight infection stresses. Several agronomic practices, such as rational use of fertilizers and optimum planting density, involved in regulating antioxidant protective enzyme systems can be regarded as promising strategy to suppress the sheath blight development. PMID- 25136672 TI - An evaluation and implementation of rule-based Home Energy Management System using the Rete algorithm. AB - In recent years, sensors become popular and Home Energy Management System (HEMS) takes an important role in saving energy without decrease in QoL (Quality of Life). Currently, many rule-based HEMSs have been proposed and almost all of them assume "IF-THEN" rules. The Rete algorithm is a typical pattern matching algorithm for IF-THEN rules. Currently, we have proposed a rule-based Home Energy Management System (HEMS) using the Rete algorithm. In the proposed system, rules for managing energy are processed by smart taps in network, and the loads for processing rules and collecting data are distributed to smart taps. In addition, the number of processes and collecting data are reduced by processing rules based on the Rete algorithm. In this paper, we evaluated the proposed system by simulation. In the simulation environment, rules are processed by a smart tap that relates to the action part of each rule. In addition, we implemented the proposed system as HEMS using smart taps. PMID- 25136673 TI - Model of close packing for determination of the major characteristics of the liquid dispersions components. AB - We introduce a close packing model of the particles from the disperse phase of a liquid dispersion. With this model, we find the sediment volumes, the emergent, and the bound dispersion medium. We formulate a new approach for determining the equivalent radii of the particles from the sediment and the emergent (different from the Stokes method). We also describe an easy manner to apply algebraic method for determining the average volumetric mass densities of the ultimate sediment and emergent, as well as the free dispersion medium (without using any pycnometers or densitometers). The masses of the different components and the density of the dispersion phase in the investigated liquid dispersion are also determined by means of the established densities. We introduce for the first time a dimensionless scale for numeric characterization and therefore an index for predicting the sedimentation stability of liquid dispersions in case of straight and/or reverse sedimentation. We also find the quantity of the pure substance (without pouring out or drying) in the dispersion phase of the liquid dispersions. PMID- 25136674 TI - Covert network analysis for key player detection and event prediction using a hybrid classifier. AB - National security has gained vital importance due to increasing number of suspicious and terrorist events across the globe. Use of different subfields of information technology has also gained much attraction of researchers and practitioners to design systems which can detect main members which are actually responsible for such kind of events. In this paper, we present a novel method to predict key players from a covert network by applying a hybrid framework. The proposed system calculates certain centrality measures for each node in the network and then applies novel hybrid classifier for detection of key players. Our system also applies anomaly detection to predict any terrorist activity in order to help law enforcement agencies to destabilize the involved network. As a proof of concept, the proposed framework has been implemented and tested using different case studies including two publicly available datasets and one local network. PMID- 25136675 TI - Protection of HEVC video delivery in vehicular networks with RaptorQ codes. AB - With future vehicles equipped with processing capability, storage, and communications, vehicular networks will become a reality. A vast number of applications will arise that will make use of this connectivity. Some of them will be based on video streaming. In this paper we focus on HEVC video coding standard streaming in vehicular networks and how it deals with packet losses with the aid of RaptorQ, a Forward Error Correction scheme. As vehicular networks are packet loss prone networks, protection mechanisms are necessary if we want to guarantee a minimum level of quality of experience to the final user. We have run simulations to evaluate which configurations fit better in this type of scenarios. PMID- 25136677 TI - Induced unbalanced linguistic ordered weighted average and its application in multiperson decision making. AB - Linguistic variables are very useful to evaluate alternatives in decision making problems because they provide a vocabulary in natural language rather than numbers. Some aggregation operators for linguistic variables force the use of a symmetric and uniformly distributed set of terms. The need to relax these conditions has recently been posited. This paper presents the induced unbalanced linguistic ordered weighted average (IULOWA) operator. This operator can deal with a set of unbalanced linguistic terms that are represented using fuzzy sets. We propose a new order-inducing criterion based on the specificity and fuzziness of the linguistic terms. Different relevancies are given to the fuzzy values according to their uncertainty degree. To illustrate the behaviour of the precision-based IULOWA operator, we present an environmental assessment case study in which a multiperson multicriteria decision making model is applied. PMID- 25136678 TI - An ant colony optimization based feature selection for web page classification. AB - The increased popularity of the web has caused the inclusion of huge amount of information to the web, and as a result of this explosive information growth, automated web page classification systems are needed to improve search engines' performance. Web pages have a large number of features such as HTML/XML tags, URLs, hyperlinks, and text contents that should be considered during an automated classification process. The aim of this study is to reduce the number of features to be used to improve runtime and accuracy of the classification of web pages. In this study, we used an ant colony optimization (ACO) algorithm to select the best features, and then we applied the well-known C4.5, naive Bayes, and k nearest neighbor classifiers to assign class labels to web pages. We used the WebKB and Conference datasets in our experiments, and we showed that using the ACO for feature selection improves both accuracy and runtime performance of classification. We also showed that the proposed ACO based algorithm can select better features with respect to the well-known information gain and chi square feature selection methods. PMID- 25136679 TI - An effective approach to improving low-cost GPS positioning accuracy in real-time navigation. AB - Positioning accuracy is a challenging issue for location-based applications using a low-cost global positioning system (GPS). This paper presents an effective approach to improving the positioning accuracy of a low-cost GPS receiver for real-time navigation. The proposed method precisely estimates position by combining vehicle movement direction, velocity averaging, and distance between waypoints using coordinate data (latitude, longitude, time, and velocity) of the GPS receiver. The previously estimated precious reference point, coordinate translation, and invalid data check also improve accuracy. In order to evaluate the performance of the proposed method, we conducted an experiment using a GARMIN GPS 19xHVS receiver attached to a car and used Google Maps to plot the processed data. The proposed method achieved improvement of 4-10 meters in several experiments. In addition, we compared the proposed approach with two other state of-the-art methods: recursive averaging and ARMA interpolation. The experimental results show that the proposed approach outperforms other state-of-the-art methods in terms of positioning accuracy. PMID- 25136680 TI - Back analysis of geomechanical parameters in underground engineering using artificial bee colony. AB - Accurate geomechanical parameters are critical in tunneling excavation, design, and supporting. In this paper, a displacements back analysis based on artificial bee colony (ABC) algorithm is proposed to identify geomechanical parameters from monitored displacements. ABC was used as global optimal algorithm to search the unknown geomechanical parameters for the problem with analytical solution. To the problem without analytical solution, optimal back analysis is time-consuming, and least square support vector machine (LSSVM) was used to build the relationship between unknown geomechanical parameters and displacement and improve the efficiency of back analysis. The proposed method was applied to a tunnel with analytical solution and a tunnel without analytical solution. The results show the proposed method is feasible. PMID- 25136681 TI - Characteristics of wind velocity and temperature change near an escarpment-shaped road embankment. AB - Artificial structures such as embankments built during the construction of highways influence the surrounding airflow. Various types of damage can occur due to changes in the wind velocity and temperature around highway embankments. However, no study has accurately measured micrometeorological changes (wind velocity and temperature) due to embankments. This study conducted a wind tunnel test and field measurement to identify changes in wind velocity and temperature before and after the construction of embankments around roads. Changes in wind velocity around an embankment after its construction were found to be influenced by the surrounding wind velocity, wind angle, and the level difference and distance from the embankment. When the level difference from the embankment was large and the distance was up to 3H, the degree of wind velocity declines was found to be large. In changes in reference wind velocities around the embankment, wind velocity increases were not proportional to the rate at which wind velocities declined. The construction of the embankment influenced surrounding temperatures. The degree of temperature change was large in locations with large level differences from the embankment at daybreak and during evening hours when wind velocity changes were small. PMID- 25136682 TI - Big data: survey, technologies, opportunities, and challenges. AB - Big Data has gained much attention from the academia and the IT industry. In the digital and computing world, information is generated and collected at a rate that rapidly exceeds the boundary range. Currently, over 2 billion people worldwide are connected to the Internet, and over 5 billion individuals own mobile phones. By 2020, 50 billion devices are expected to be connected to the Internet. At this point, predicted data production will be 44 times greater than that in 2009. As information is transferred and shared at light speed on optic fiber and wireless networks, the volume of data and the speed of market growth increase. However, the fast growth rate of such large data generates numerous challenges, such as the rapid growth of data, transfer speed, diverse data, and security. Nonetheless, Big Data is still in its infancy stage, and the domain has not been reviewed in general. Hence, this study comprehensively surveys and classifies the various attributes of Big Data, including its nature, definitions, rapid growth rate, volume, management, analysis, and security. This study also proposes a data life cycle that uses the technologies and terminologies of Big Data. Future research directions in this field are determined based on opportunities and several open issues in Big Data domination. These research directions facilitate the exploration of the domain and the development of optimal techniques to address Big Data. PMID- 25136676 TI - Vascular calcification and renal bone disorders. AB - At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC. PMID- 25136683 TI - Quality of protection evaluation of security mechanisms. AB - Recent research indicates that during the design of teleinformatic system the tradeoff between the systems performance and the system protection should be made. The traditional approach assumes that the best way is to apply the strongest possible security measures. Unfortunately, the overestimation of security measures can lead to the unreasonable increase of system load. This is especially important in multimedia systems where the performance has critical character. In many cases determination of the required level of protection and adjustment of some security measures to these requirements increase system efficiency. Such an approach is achieved by means of the quality of protection models where the security measures are evaluated according to their influence on the system security. In the paper, we propose a model for QoP evaluation of security mechanisms. Owing to this model, one can quantify the influence of particular security mechanisms on ensuring security attributes. The methodology of our model preparation is described and based on it the case study analysis is presented. We support our method by the tool where the models can be defined and QoP evaluation can be performed. Finally, we have modelled TLS cryptographic protocol and presented the QoP security mechanisms evaluation for the selected versions of this protocol. PMID- 25136684 TI - (n - 1)-Step derivations on n-groupoids: the case n = 3. AB - We define a ranked trigroupoid as a natural followup on the idea of a ranked bigroupoid. We consider the idea of a derivation on such a trigroupoid as representing a two-step process on a pair of ranked bigroupoids where the mapping d is a self-derivation at each step. Following up on this idea we obtain several results and conclusions of interest. We also discuss the notion of a couplet (D, d) on X, consisting of a two-step derivation d and its square D = d ? d, for example, whose defining property leads to further observations on the underlying ranked trigroupoids also. PMID- 25136685 TI - Minimize the percentage of noise in biomedical images using neural networks. AB - The overall goal of the research is to improve the quality of biomedical image for telemedicine with minimum percentages of noise in the retrieved image and to take less computation time. The novelty of this technique lies in the implementation of spectral coding for biomedical images using neural networks in order to accomplish the above objectives. This work is in continuity of an ongoing research project aimed at developing a system for efficient image compression approach for telemedicine in Saudi Arabia. We compare the efficiency of this technique against existing image compression techniques, namely, JPEG2000, in terms of compression ratio, peak signal to noise ratio (PSNR), and computation time. To our knowledge, the research is the primary in providing a comparative study with other techniques used in the compression of biomedical images. This work explores and tests biomedical images such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). PMID- 25136687 TI - Fire propagation performance of intumescent fire protective coatings using eggshells as a novel biofiller. AB - This paper aims to synthesize and characterize an effective intumescent fire protective coating that incorporates eggshell powder as a novel biofiller. The performances of thermal stability, char formation, fire propagation, water resistance, and adhesion strength of coatings have been evaluated. A few intumescent flame-retardant coatings based on these three ecofriendly fire retardant additives ammonium polyphosphate phase II, pentaerythritol and melamine mixed together with flame-retardant fillers, and acrylic binder have been prepared and designed for steel. The fire performance of the coatings has conducted employing BS 476: Part 6-Fire propagation test. The foam structures of the intumescent coatings have been observed using field emission scanning electron microscopy. On exposure, the coated specimens' B, C, and D had been certified to be Class 0 due to the fact that their fire propagation indexes were less than 12. Incorporation of ecofriendly eggshell, biofiller into formulation D led to excellent performance in fire stopping (index value, (I) = 4.3) and antioxidation of intumescent coating. The coating is also found to be quite effective in water repellency, uniform foam structure, and adhesion strength. PMID- 25136686 TI - Lymphocyte oxidative stress/genotoxic effects are related to serum IgG and IgA levels in coke oven workers. AB - We investigated oxidative stress/genotoxic effects levels, immunoglobulin levels, polycyclic aromatic hydrocarbons (PAHs) levels exposed in 126 coke oven workers and in 78 control subjects, and evaluated the association between oxidative stress/genotoxic effects levels and immunoglobulin levels. Significant differences were observed in biomarkers, including 1-hydroxypyrene levels, employment time, percentages of alcohol drinkers, MDA, 8-OHdG levels, CTL levels and CTM, MN, CA frequency, and IgG, IgA levels between the control and exposed groups. Slightly higher 1-OHP levels in smoking users were observed. For the dose response relationship of IgG, IgA, IgM, and IgE by 1-OHP, each one percentage increase in urinary 1-OHP generates a 0.109%, 0.472%, 0.051%, and 0.067% decrease in control group and generates a 0.312%, 0.538%, 0.062%, and 0.071% decrease in exposed group, respectively. Except for age, alcohol and smoking status, IgM, and IgE, a significant correlation in urinary 1-OHP and other biomarkers in the total population was observed. Additionally, a significant negative correlation in genotoxic/oxidative damage biomarkers of MDA, 8-OH-dG, CTL levels, and immunoglobins of IgG and IgA levels, especially in coke oven workers, was found. These data suggest that oxidative stress/DNA damage induced by PAHs may play a role in toxic responses for PAHs in immunological functions. PMID- 25136688 TI - Automating risk analysis of software design models. AB - The growth of the internet and networked systems has exposed software to an increased amount of security threats. One of the responses from software developers to these threats is the introduction of security activities in the software development lifecycle. This paper describes an approach to reduce the need for costly human expertise to perform risk analysis in software, which is common in secure development methodologies, by automating threat modeling. Reducing the dependency on security experts aims at reducing the cost of secure development by allowing non-security-aware developers to apply secure development with little to no additional cost, making secure development more accessible. To automate threat modeling two data structures are introduced, identification trees and mitigation trees, to identify threats in software designs and advise mitigation techniques, while taking into account specification requirements and cost concerns. These are the components of our model for automated threat modeling, AutSEC. We validated AutSEC by implementing it in a tool based on data flow diagrams, from the Microsoft security development methodology, and applying it to VOMS, a grid middleware component, to evaluate our model's performance. PMID- 25136690 TI - A fuzzy-decision based approach for Composite event detection in wireless sensor networks. AB - The event detection is one of the fundamental researches in wireless sensor networks (WSNs). Due to the consideration of various properties that reflect events status, the Composite event is more consistent with the objective world. Thus, the research of the Composite event becomes more realistic. In this paper, we analyze the characteristics of the Composite event; then we propose a criterion to determine the area of the Composite event and put forward a dominating set based network topology construction algorithm under random deployment. For the unreliability of partial data in detection process and fuzziness of the event definitions in nature, we propose a cluster-based two dimensional tau-GAS algorithm and fuzzy-decision based composite event decision mechanism. In the case that the sensory data of most nodes are normal, the two dimensional tau-GAS algorithm can filter the fault node data effectively and reduce the influence of erroneous data on the event determination. The Composite event judgment mechanism which is based on fuzzy-decision holds the superiority of the fuzzy-logic based algorithm; moreover, it does not need the support of a huge rule base and its computational complexity is small. Compared to CollECT algorithm and CDS algorithm, this algorithm improves the detection accuracy and reduces the traffic. PMID- 25136689 TI - Effect of intra-articular hyaluronic injection on postural stability and risk of fall in patients with bilateral knee osteoarthritis. AB - Knee osteoarthritis is a common cause of disability which influences the quality of life. It is associated with impaired knee joint proprioception, which affects postural stability. Postural stability is critical for mobility and physical activities. Different types of treatment including nonsurgical and surgical are used for knee osteoarthritis. Hyaluronic acid injection is a nonsurgical popular treatment used worldwide. The aim of this study was to demonstrate the effect of hyaluronic acid injections on postural stability in individuals with bilateral knee osteoarthritis. Fifty patients aged between 50 and 70 years with mild and moderate bilateral knee osteoarthritis participated in our study. They were categorized into treatment (n = 25) and control (n = 25) groups. The treatment group received five weekly hyaluronic acid injections for both knees, whereas the control group did not receive any treatment. Postural stability and fall risk were assessed using the Biodex Stability System and clinical "Timed Up and Go" test. All the participants completed the study. The treatment group showed significant decrease in postural stability and fall risk scores after five hyaluronic acid injections. In contrast, the control group showed significant increase. This study illustrated that five intra-articular hyaluronic acid injections could significantly improve postural stability and fall risk in bilateral knee osteoarthritis patients. This trial is registered with: NCT02063373. PMID- 25136692 TI - On Poisson nonlinear transformations. AB - We construct the family of Poisson nonlinear transformations defined on the countable sample space of nonnegative integers and investigate their trajectory behavior. We have proved that these nonlinear transformations are regular. PMID- 25136691 TI - Comparison of internal fixations for distal clavicular fractures based on loading tests and finite element analyses. AB - It is difficult to apply strong and stable internal fixation to a fracture of the distal end of the clavicle because it is unstable, the distal clavicle fragment is small, and the fractured region is near the acromioclavicular joint. In this study, to identify a superior internal fixation method for unstable distal clavicular fracture, we compared three types of internal fixation (tension band wiring, scorpion, and LCP clavicle hook plate). Firstly, loading tests were performed, in which fixations were evaluated using bending stiffness and torsional stiffness as indices, followed by finite element analysis to evaluate fixability using the stress and strain as indices. The bending and torsional stiffness were significantly higher in the artificial clavicles fixed with the two types of plate than in that fixed by tension band wiring (P < 0.05). No marked stress concentration on the clavicle was noted in the scorpion because the arm plate did not interfere with the acromioclavicular joint, suggesting that favorable shoulder joint function can be achieved. The stability of fixation with the LCP clavicle hook plate and the scorpion was similar, and plate fixations were stronger than fixation by tension band wiring. PMID- 25136693 TI - Mutation and chaos in nonlinear models of heredity. AB - We shall explore a nonlinear discrete dynamical system that naturally occurs in population systems to describe a transmission of a trait from parents to their offspring. We consider a Mendelian inheritance for a single gene with three alleles and assume that to form a new generation, each gene has a possibility to mutate, that is, to change into a gene of the other kind. We investigate the derived models and observe chaotic behaviors of such models. PMID- 25136694 TI - Enhancement of the wear resistance and microhardness of aluminum alloy by Nd:YaG laser treatment. AB - Influence of laser treatment on mechanical properties, wear resistance, and Vickers hardness of aluminum alloy was studied. The specimens were treated by using Nd:YaG laser of energy 780 mj, wavelength 512 nm, and duration time 8 ns. The wear behavior of the specimens was studied for all specimens before and after treatment by Nd:YaG laser and the dry wear experiments were carried out by sing pinon-disc technique. The specimens were machined as a disk with diameter of 25 mm and circular groove in depth of 3 mm. All specimens were conducted by scanning electron microscopy (SEM), energy-dispersive X-ray fluorescence analysis (EDS), optical microscopy, and Vickers hardness. The results showed that the dry wear rate was decreased after laser hardening and increased Vickers hardness values by ratio of 2.4:1. The results showed that the values of wear rate for samples having circular grooves are less than samples without grooves after laser treatment. PMID- 25136695 TI - PLUNC proteins positivity in patients with chronic rhinosinusitis: a case-control study. AB - INTRODUCTION: Innate immunity is the first protection against microorganisms. Nowadays, there is a growing interest in innate immune molecule known as palate, lung, nasal epithelial clone (PLUNC). PLUNC is a specific product of the airways, of approximately 25 kDa, encoded by adjacent genes found within a 300 kb region of chromosome 20; these proteins must be detected predominantly in the upper respiratory tract. MATERIALS AND METHODS: We performed a case-control study to investigate the presence of this protein in nasal tissue of patients affected by chronic rhinosinusitis. 59 patients were enrolled (44 cases, 15 controls). We have examined the correlation between the presence of pathology and the PLUNC proteins positivity. RESULTS: 100% of controls have a +++ rated PLUNC proteins positivity, while cases have a lower percentage of positivity. We used chi (2) statistical test to analyze the results of the study and there is a difference statistically significant between cases and controls in PLUNC proteins positivity. CONCLUSIONS: These observations suggest that, in response to agents or chemical factors, nasal mucosal epithelium will react and produce PLUNC proteins. So PLUNC proteins have a protective function on upper airways mucosa, as we can see by evaluating the high positivity in control group. PMID- 25136696 TI - Carbon dioxide absorption and release properties of pyrolysis products of dolomite calcined in vacuum atmosphere. AB - The decomposition of dolomite into CaO and MgO was performed at 1073 K in vacuum and at 1273 K in an Ar atmosphere. The dolomite calcined in vacuum was found to have a higher specific surface area and a higher micropore volume when compared to the dolomite calcined in the Ar atmosphere. These pyrolysis products of dolomite were reacted with CO2 at 673 K for 21.6 ks. On the absorption of CO2, the formation of CaCO3 was observed. The degree of absorption of the dolomite calcined in vacuum was determined to be above 50%, which was higher than the degree of absorption of the dolomite calcined in the Ar atmosphere. The CO2 absorption and release procedures were repeated three times for the dolomite calcined in vacuum. The specific surface area and micropore volume of calcined dolomite decreased with successive repetitions of the CO2 absorption and release cycles leading to a decrease in the degree of absorption of CO2. PMID- 25136697 TI - A secure 3-way routing protocols for intermittently connected mobile ad hoc networks. AB - The mobile ad hoc network may be partially connected or it may be disconnected in nature and these forms of networks are termed intermittently connected mobile ad hoc network (ICMANET). The routing in such disconnected network is commonly an arduous task. Many routing protocols have been proposed for routing in ICMANET since decades. The routing techniques in existence for ICMANET are, namely, flooding, epidemic, probabilistic, copy case, spray and wait, and so forth. These techniques achieve an effective routing with minimum latency, higher delivery ratio, lesser overhead, and so forth. Though these techniques generate effective results, in this paper, we propose novel routing algorithms grounded on agent and cryptographic techniques, namely, location dissemination service (LoDiS) routing with agent AES, A-LoDiS with agent AES routing, and B-LoDiS with agent AES routing, ensuring optimal results with respect to various network routing parameters. The algorithm along with efficient routing ensures higher degree of security. The security level is cited testing with respect to possibility of malicious nodes into the network. This paper also aids, with the comparative results of proposed algorithms, for secure routing in ICMANET. PMID- 25136698 TI - The Polya-Szego principle and the anisotropic convex Lorentz-Sobolev inequality. AB - An anisotropic convex Lorentz-Sobolev inequality is established, which extends Ludwig, Xiao, and Zhang's result to any norm from Euclidean norm, and the geometric analogue of this inequality is given. In addition, it implies that the (anisotropic) Polya-Szego principle is shown. PMID- 25136699 TI - A hybrid wavelet transform based short-term wind speed forecasting approach. AB - It is important to improve the accuracy of wind speed forecasting for wind parks management and wind power utilization. In this paper, a novel hybrid approach known as WTT-TNN is proposed for wind speed forecasting. In the first step of the approach, a wavelet transform technique (WTT) is used to decompose wind speed into an approximate scale and several detailed scales. In the second step, a two hidden-layer neural network (TNN) is used to predict both approximated scale and detailed scales, respectively. In order to find the optimal network architecture, the partial autocorrelation function is adopted to determine the number of neurons in the input layer, and an experimental simulation is made to determine the number of neurons within each hidden layer in the modeling process of TNN. Afterwards, the final prediction value can be obtained by the sum of these prediction results. In this study, a WTT is employed to extract these different patterns of the wind speed and make it easier for forecasting. To evaluate the performance of the proposed approach, it is applied to forecast Hexi Corridor of China's wind speed. Simulation results in four different cases show that the proposed method increases wind speed forecasting accuracy. PMID- 25136700 TI - Image inpainting methods evaluation and improvement. AB - With the upgrowing of digital processing of images and film archiving, the need for assisted or unsupervised restoration required the development of a series of methods and techniques. Among them, image inpainting is maybe the most impressive and useful. Based on partial derivative equations or texture synthesis, many other hybrid techniques have been proposed recently. The need for an analytical comparison, beside the visual one, urged us to perform the studies shown in the present paper. Starting with an overview of the domain, an evaluation of the five methods was performed using a common benchmark and measuring the PSNR. Conclusions regarding the performance of the investigated algorithms have been presented, categorizing them in function of the restored image structure. Based on these experiments, we have proposed an adaptation of Oliveira's and Hadhoud's algorithms, which are performing well on images with natural defects. PMID- 25136701 TI - Computational fluid dynamics modelling of microfluidic channel for dielectrophoretic BioMEMS application. AB - We propose a strategy for optimizing distribution of flow in a typical benchtop microfluidic chamber for dielectrophoretic application. It is aimed at encouraging uniform flow velocity along the whole analysis chamber in order to ensure DEP force is evenly applied to biological particle. Via the study, we have come up with a constructive strategy in improving the design of microfluidic channel which will greatly facilitate the use of DEP system in laboratory and primarily focus on the relationship between architecture and cell distribution, by resorting to the tubular structure of blood vessels. The design was validated by hydrodynamic flow simulation using COMSOL Multiphysics v4.2a software. Simulations show that the presence of 2-level bifurcation has developed portioning of volumetric flow which produced uniform flow across the channel. However, further bifurcation will reduce the volumetric flow rate, thus causing undesirable deposition of cell suspension around the chamber. Finally, an improvement of microfluidic design with rounded corner is proposed to encourage a uniform cell adhesion within the channel. PMID- 25136702 TI - Thermodynamic analysis and optimization of a high temperature triple absorption heat transformer. AB - First law of thermodynamics has been used to analyze and optimize inclusively the performance of a triple absorption heat transformer operating with LiBr/H2O as the working pair. A thermodynamic model was developed in EES (engineering equation solver) to estimate the performance of the system in terms of the most essential parameters. The assumed parameters are the temperature of the main components, weak and strong solutions, economizers' efficiencies, and bypass ratios. The whole cycle is optimized by EES software from the viewpoint of maximizing the COP via applying the direct search method. The optimization results showed that the COP of 0.2491 is reachable by the proposed cycle. PMID- 25136703 TI - Label-free in vitro visualization of particle uptake into human oral buccal epithelial cells by confocal Raman microscopy. AB - In this study, we present confocal Raman microscopy for chemically selective analysis of a human buccal epithelial cell layer with a focus on label-free visualization of particle uptake into the cells. We demonstrate the suitability and benefit of this analytical technique in comparison to confocal fluorescence microscopy for three dimensional imaging of in vitro cell models. PMID- 25136704 TI - Association of provider-patient visit frequency and patient outcomes on hemodialysis. PMID- 25136705 TI - Unraveling the chemistry of the glomerular basement membrane. PMID- 25136706 TI - Bortezomib, lenalidomide and dexamethasone (VRD) combination as salvage therapy in refractory angioimmunoblastic T cell lymphoma. PMID- 25136707 TI - Reflections: neurology and the humanities. A soliloquy in LP humility. PMID- 25136708 TI - Author response. PMID- 25136709 TI - Author response. PMID- 25136710 TI - Photosynthetic efficiency and carbon concentration in terrestrial plants: the C4 and CAM solutions. PMID- 25136711 TI - Cholera, 2013. PMID- 25136712 TI - Health conditions for travellers to Saudi Arabia for the pilgrimage to Mecca (Hajj), 2014. PMID- 25136713 TI - Congress stalls on BRAIN Initiative funding. PMID- 25136715 TI - Of pigs and people--WHO prepares to battle cysticercosis. PMID- 25136714 TI - EC Chief Scientific Adviser position gets strong backing. PMID- 25136716 TI - The Lancet Technology: August, 2014. Surgical training through the looking Glass. PMID- 25136718 TI - Carlos Ribeiro. PMID- 25136717 TI - Closing the carbon cycle. PMID- 25136719 TI - The age of miracles. PMID- 25136720 TI - Donald Nixon Ross. PMID- 25136721 TI - Global Polio Eradication Initiative: 10th meeting of the Independent Monitoring Board. PMID- 25136722 TI - Monthly report on dracunculiasis cases, January-June 2014. PMID- 25136723 TI - Authors' reply. PMID- 25136724 TI - Authors' reply. PMID- 25136725 TI - Possession of objectionable material (Med 12/228P). PMID- 25136726 TI - Reply to Tai: On the inability of 10 soloists to tell apart Old Italian and new violins at better than chance levels. PMID- 25136727 TI - Review of the Blastobasinae of Costa Rica (Lepidoptera: Gelechioidea: Blastobasidae). AB - The Blastobasinae (Lepidoptera: Gelechioidea: Blastobasidae) of Costa Rica are reviewed. Five new genera, Barbaloba, Hallicis, Koleps, Pheos, and Pseudokoleps, and 101 new species are described. They include: Barbaloba jubae, B. meleagrisellae, Hallicis bisetosellus, H. calvicula, Koleps angulatus, Pheos aculeatus, Pseudokoleps akainae, Blastobasis abollae, B. achaea, B. aedes, B. babae, B. balucis, B. beo, B. caetrae, B. chanes, B. custodis, B. dapis, B. deae, B. deliciolarum, B. dicionis, B. echus, B. erae, B. fax, B. furtivus, B. iuanae, B. lex, B. litis, B. lygdi, B. manto, B. neniae, B. nivis, B. orithyia, B. paludis, B. phaedra, B. rotae, B. rotullae, B. tapetae, B. thyone, B. usurae, B. vesta, B. xiphiae, Hypatopa actes, H. acus, H. agnae, H. arxcis, H. bilobata, H. caedis, H. caepae, H. cladis, H. cotis, H. cotytto, H. crux, H. cyane, H. dicax, H. dolo, H. dux, H. edax, H. eos, H. erato, H. fio, H. gena, H. hecate, H. hera, H. hora, H. io, H. ira, H. leda, H. limae, H. lucina, H. joniella, H. juno, H. manus, H. mora, H. musa, H. nex, H. nox, H. phoebe, H. pica, H. plebis, H. rabio, H. rea, H. rego, H. rudis, H. sais, H. scobis, H. semela, H. solea, H. styga, H. texla, H. texo, H. umbra, H. verax, H. vitis, H. vox, Pigritia dido, P. faux, P. gruis, P. haha, P. sedis, P. stips, and P. ululae. Diagnoses, descriptions, and type data are provided for each species. Photographs of imagos, illustrations of wing venation for selected species, male and female genitalia, and distribution maps are furnished. Keys to all genera in Blastobasinae and keys to all species within each genus are provided to assist with identifications. In addition, scanning electron micrographs of the inner surface of the dilated first antennal flagellomere and associated sex scales for all Blastobasis are provided. Blastobasis coffeaella (Busck, 1925), B. graminea Adamski, 1999, Hypatopa tapadulcea Adamski, 1999, and Pigritia marjoriella Adamski, 1998 are redescribed. PMID- 25136728 TI - Revision of the genus Erythromelana Townsend (Diptera: Tachinidae) and analysis of its phylogeny and diversification. AB - The Neotropics harbor an enormous diversity of tachinid flies (Diptera: Tachinidae), yet the fauna remains poorly understood. This is especially true of the tribe Blondeliini, which is particularly diverse in this region and in great need of taxonomic attention. Here, the Neotropical blondeliine genus Erythromelana Townsend is revised. This genus is widely distributed from southern Mexico to northern Argentina, with the Andes being a hotspot of diversity. Known hosts belong to the genus Eois Hubner (Lepidoptera: Geometridae). This revision includes the redescription of three previously described species and the description of 11 new species based on characteristics of adults and immatures. The new species are E. arciforceps sp. nov., E. catarina sp. nov., E. convexiforceps sp. nov., E. cryptica sp. nov., E. curvifrons sp. nov., E. distincta sp. nov., E. ecuadoriana sp. nov., E. eois sp. nov., E. leptoforceps sp. nov., E. napensis sp. nov., and E. woodi sp. nov. A morphological database of 62 characters was constructed to assess morphological variation within and among species and species groups using Principal Components Analysis. Means and medians for these morphological traits were calculated to infer phylogenetic relationships using parsimony. Additionally, a maximum likelihood phylogenetic analysis was performed using COI mtDNA sequences for a subset of eight species. Nominal species E. obscurifrons (Wulp) is treated as a nomen dubium within Erythromelana. Two species previously assigned to Erythromelana appear to represent distinct genera with unclear relationships to this genus and are reinstated as monotypic genera: Myiodoriops marginalis Townsend and Euptilodegeeria obumbrata (Wulp), revived status. Biological and phylogenetic data are used to infer modes of diversification within Erythromelana. PMID- 25136730 TI - Preface: occupational diseases. PMID- 25136729 TI - Current progress in Reactive Oxygen Species (ROS)-Responsive materials for biomedical applications. AB - Recently, significant progress has been made in developing "stimuli-sensitive" biomaterials as a new therapeutic approach to interact with dynamic physiological conditions. Reactive oxygen species (ROS) production has been implicated in important pathophysiological events, such as atherosclerosis,aging, and cancer. ROS are often overproduced locally in diseased cells and tissues, and they individually and synchronously contribute to many of the abnormalities associated with local pathogenesis. Therefore, the advantages of developing ROS-responsive materials extend beyond site-specific targeting of therapeutic delivery, and potentially include navigating,sensing, and repairing the cellular damages via programmed changes in material properties. Here we review the mechanism and development of biomaterials with ROS-induced solubility switch or degradation, as well as their performance and potential for future biomedical applications. PMID- 25136731 TI - Sex differences in the modulation of emotional processing by expectation. AB - Many studies have reported sex differences in processing emotional events, the valence of which are unknown in advance. The present study examined whether women and men differ in processing emotional events when they do have such expectations. Event-related potentials were recorded when participants were presented with emotional pictures, the valence of which was either expected or unexpected. For women, the modulation effect by expectation was found on the early N2 response; for men, the effect was found on the late positive component. Implications are discussed in light of evolutionary theories. PMID- 25136733 TI - A rare cause of lower back pain. PMID- 25136735 TI - 15 largest healthcare real estate investment trusts. Publicly traded healthcare REITs ranked by market capitalization, as of May 31. PMID- 25136734 TI - Blasts with rosette-like multinucleation in acute myeloid leukemia with complex cytogenetic abnormalities. PMID- 25136736 TI - Accountable care organizations by state. The number of accountable care organizations per state, ranked by total number of ACOs. PMID- 25136738 TI - Largest healthcare law firms. Based on a blended score of healthcare lawyers employed in 2013 and AHLA membership as of June 5. PMID- 25136739 TI - Bromination and accompanying rearrangement of the polycyclic oxetane 2,4 oxytwistane. AB - Bromination of the polycyclic oxetane 2,4-oxytwistane (rac-(1R,3S,4R,7S,9R,11S)-2 oxatetracyclo[5.3.1.0(3,11).0(4,9)]undecane) was undertaken in order to form 2,4 dibromotwistane. The oxetane was subjected to the mild reagent combination CBr4/Ph3P in a fashion similar to that for the Appel and Corey-Fuchs reactions. NMR spectroscopy revealed that the isomeric dibromo compound 2,8 dibromoisotwistane (2,8-dibromotricyclo[4.3.1.0(3,7)]decane) was inadvertently formed. The conversion was prevented by migration of a C-C bond within the geometrically stressed C10 framework. Computational chemistry was used to model the structure of the polycyclic oxetane and to assess the component of total ring strain energy due to the four-membered heterocycle. Mechanistic aspects behind the skeletal rearrangement are also discussed. PMID- 25136737 TI - Franz Kafka and the doctor's dilemma. PMID- 25136740 TI - Structurally nanocrystalline-electrically single crystalline ZnO-reduced graphene oxide composites. AB - ZnO, a wide bandgap semiconductor, has attracted much attention due to its multifunctionality, such as transparent conducting oxide, light-emitting diode, photocatalyst, and so on. To improve its performances in the versatile applications, numerous hybrid strategies of ZnO with graphene have been attempted, and various synergistic effects have been achieved in the ZnO-graphene hybrid nanostructures. Here we report extraordinary charge transport behavior in Al-doped ZnO (AZO)-reduced graphene oxide (RGO) nanocomposites. Although the most challenging issue in semiconductor nanocomposites is their low mobilities, the AZO-RGO nanocomposites exhibit single crystal-like Hall mobility despite the large quantity of nanograin boundaries, which hinder the electron transport by the scattering with trapped charges. Because of the significantly weakened grain boundary barrier and the proper band alignment between the AZO and RGO, freely conducting electrons across the nanograin boundaries can be realized in the nanocomposites. This discovery of the structurally nanocrystalline-electrically single crystalline composite demonstrates a new route for enhancing the electrical properties in nanocomposites based on the hybrid strategy. PMID- 25136742 TI - Tuning the gelation ability of racemic mixture by melamine: enhanced mechanical rigidity and tunable nanoscale chirality. AB - Understanding the relationship between molecular chirality of the gelators and the properties of the assembled supramolecular gels could be very important for developing novel functional soft matters. Although mixing the enantiomers with different molar ratios has been proved to be useful for modulating supramolecular assemblies, usually the racemates of different chiral molecules are not good gelators. In this study, the coassembly of the glutamic acid-based bolaamphiphile racemate and melamine was found to form hydrogels, while the assembly of the racemate only produced precipitates. Remarkably, the racemic hydrogels show lower CGC value, enhanced mechanical rigidity, and dual pH-responsive ability compared to the pure enantiomer hydrogels. The gelation properties, nanoscale chirality, and nanostructures of the racemic hydrogels can be regulated flexibly by changing molar ratios of different molecular building blocks. PMID- 25136743 TI - Dye-sensitized solar cells employing doubly or singly open-ended TiO2 nanotube arrays: structural geometry and charge transport. AB - We systematically investigated the charge transport properties of doubly or singly open-ended TiO2 nanotube arrays (DNT and SNT, respectively) for their utility as electrodes in dye-sensitized solar cells (DSCs). The SNT or DNT arrays were transferred in a bottom-up (B-up) or top-up (T-up) configuration onto a fluorine-doped tin oxide (FTO) substrate onto which had been deposited a 2 MUm thick TiO2 nanoparticle (NP) interlayer. This process yielded four types of DSCs prepared with SNTs (B-up or T-up) or DNT (B-up or T-up). The photovoltaic performances of these DSCs were analyzed by measuring the dependence of the charge transport on the DSC geometry. High resolution scanning electron microscopy techniques were used to characterize the electrode cross sections, and electrochemical impedance spectroscopy was used to characterize the electrical connection at the interface between the NT array and the TiO2 NP interlayer. We examined the effects of decorating the DNT or SNT arrays with small NPs (sNP@DNT and sNP@SNT, respectively) in an effort to increase the extent of dye loading. The DNT arrays decorated with small NPs performed better than the decorated SNT arrays, most likely because the Ti(OH)4 precursor solution flowed freely into the array through the open ends of the NTs in the DNT case but not in the SNT case. The sNP@DNT-based DSC exhibited a better PCE (10%) compared to the sNP@SNT-based DSCs (6.8%) because the electrolyte solution flow was not restricted, direct electron transport though the NT arrays was possible, the electrical connection at the interface between the NT array and the TiO2 NP interlayer was good, and the array provided efficient light harvesting. PMID- 25136741 TI - Discovery of a chemical modification by citric acid in a recombinant monoclonal antibody. AB - Recombinant therapeutic monoclonal antibodies exhibit a high degree of heterogeneity that can arise from various post-translational modifications. The formulation for a protein product is to maintain a specific pH and to minimize further modifications. Generally Recognized as Safe (GRAS), citric acid is commonly used for formulation to maintain a pH at a range between 3 and 6 and is generally considered chemically inert. However, as we reported herein, citric acid covalently modified a recombinant monoclonal antibody (IgG1) in a phosphate/citrate-buffered formulation at pH 5.2 and led to the formation of so called "acidic species" that showed mass increases of 174 and 156 Da, respectively. Peptide mapping revealed that the modification occurred at the N terminus of the light chain. Three additional antibodies also showed the same modification but displayed different susceptibilities of the N-termini of the light chain, heavy chain, or both. Thus, ostensibly unreactive excipients under certain conditions may increase heterogeneity and acidic species in formulated recombinant monoclonal antibodies. By analogy, other molecules (e.g., succinic acid) with two or more carboxylic acid groups and capable of forming an anhydride may exhibit similar reactivities. Altogether, our findings again reminded us that it is prudent to consider formulations as a potential source for chemical modifications and product heterogeneity. PMID- 25136744 TI - Oxidation of bromophenols and formation of brominated polymeric products of concern during water treatment with potassium permanganate. AB - The extensive use of bromophenols (BrPs) in industrial products leads to their occurrence in freshwater environments. This study explored the oxidation kinetics of several BrPs (i.e., 2-BrP, 3-BrP, 4-BrP, 2,4-diBrP, and 2,6-diBrP) and potential formation of brominated polymeric products of concern during water treatment with potassium permanganate [Mn(VII)]. These BrPs exhibited appreciable reactivity toward Mn(VII) with the maxima of second-order rate constants (kMn(VII)) at pH near their pKa values, producing bell-shaped pH-rate profiles. The unusual pH-dependency of kMn(VII) was reasonably explained by a tentative reaction model, where the formation of an intermediate between Mn(VII) and dissociated BrP was likely involved. A novel and powerful precursor ion scan (PIS) approach was used for selective detection of brominated oxidation products by liquid chromatography/electrospray ionization-triple quadrupole mass spectrometry. Results showed that brominated dimeric products such as hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and hydroxylated polybrominated biphenyls (OH-PBBs) were readily produced. For instance, 2'-OH-BDE 68, one of the most naturally abundant OH-PBDEs, could be formed at a relatively high yield possibly via the coupling between bromophenoxyl radicals generated from the one-electron oxidation of 2,4-diBrP by Mn(VII). Given the altered or enhanced toxicological effects of these brominated polymeric products compared to the BrP precursors, it is important to better understand their reactivity and fate before Mn(VII) is applied by water utilities for the oxidative treatment of BrP-containing waters. PMID- 25136745 TI - Stimulation of cannabinoid receptors by using Rubus coreanus extracts to control osteoporosis in aged male rats. AB - A substantial proportion of men with prostatic disease have an increased risk of bone loss. In the present study, we investigated the effects of Rubus coreanus Miquel (RCM) extracts on osteoporosis that occurs with N-methyl-N-nitrosourea (MNU)-induced prostatic hyperplasia. The rats used in this study were categorized into groups of healthy controls, rats treated with MNU, and rats treated with MNU and RCM. The rats were sacrificed after 10 weeks of RCM treatment, after which ultrasonography, serum biochemical tests, histopathological examinations, immunohistochemical analysis, and semi-quantitative reverse-transcription polymerase chain reaction analysis were performed. There were no marked differences in body weight gain and the size and weight of the prostate gland between the MNU group and the MNU and RCM group. However, treatment with RCM inhibited osteoclastic osteolysis and reduced dysplastic progress in the prostate gland, as observed by histopathological evaluation and by analyzing changes in the levels of bone regulatory factors. In addition, the group treated with MNU and RCM had higher expression levels of cannabinoid receptors-1, -2, and osteoprotegerin. These results indicate that the anti-osteoporotic effect of RCM in prostatic hyperplasia is attributable to the cannabinoid receptor-related upregulation of osteoblastogenesis and inhibition of prostatic hyperplasia. The results of the present study suggest that treatment with RCM may benefit osteoporotic patients with prostatic disease by simultaneously altering the activation of osteoblasts and osteoclasts. PMID- 25136746 TI - Additional correction of OAB symptoms by two anti-muscarinics for men over 50 years old with residual symptoms of moderate prostatic obstruction after treatment with Tamsulosin. AB - OBJECTIVES: To study the effectiveness and safety of combined standard-dosed Solifenacin and Trospium for management of symptoms of overactive bladder (OAB) in elderly patients after the treatment with Tamsulosin. PATIENTS AND METHODS: A total of 417 men over 50 years of age (average age 57.9 (8.3)) with diagnosed prostatic obstruction (score 8-19 according to I-PSS), who had not taken Tamsulosin before, were enrolled in the study. I-PSS questionnaire (from 8 to 19 moderate) and Awareness Tool questionnaire for evaluating OAB symptoms (total score for OAB symptoms over 8) were used at the beginning and at the end of the observation. Also, urodynamic parameters were examined. RESULT: Percentage of patients with prevalent symptoms of obstruction of urethra decreases after the treatment with Tamsulosin and then rises again (36.2%), but absolute number of patients remains smaller than initial data. Percentage of patients with relative prevalence of symptoms of overactive bladder slightly increases against administration of Tamsulosin and reaches initial values at the time of administration of anti-muscarinic drugs with absolute decrease in number of such patients. CONCLUSION: Combination of Trospium and Solifenacin is an effective way to manage residual symptoms of hyperactive bladder during treatment of early obstruction of urinary bladder. PMID- 25136747 TI - Routine screening for postnatal depression in a public health family service unit: a retrospective study of self-excluding women. AB - At this time, there is limited scientific knowledge about women who exclude themselves from screening programs for postnatal depression. In this retrospective descriptive study, we have sought to investigate the socio demographic and psycho-social factors of women who withdraw from PND screening of their own accord. Study participants were 525 women attending antenatal classes who later took part in institutional routine screening for PND at the Consultorio Familiare Service of the National Health Service, Italy. The PND screening program consisted of the completion of the postpartum depression predictors inventory-revised and psychological well-being (PWB) questionnaires within eight to nine months of pregnancy, and Edinburgh Postnatal Depression Scale, GHQ-12 and PWB within six to eight weeks after childbirth. The Responders group was made up of 346 subjects - 65.9% of the total sample - who completed the entire program of screening for PND. The Non-Responders group, on the other hand, consisted of 179 subjects - 34.1% of the total sample - who, after childbirth, withdrew from the screening program. Compared to the Responders group, the Non-Responders group showed a greater number of subjects with marital dissatisfaction, and with unemployment as a stressful event. Health professionals who detect marital dissatisfaction and/or unemployment as a stressful event in pregnant women should bear in mind that these individuals, besides being at high risk for depression after delivery, will also tend to exclude themselves from screening for PND. PMID- 25136748 TI - Successful transportation of precious cargo: becoming an expert neonatal transport nurse. PMID- 25136749 TI - Responding to traumatic birth: subgaleal hemorrhage, assessment, and management during transport. AB - Subgaleal hemorrhage is an uncommon but often fatal complication of a traumatic birth. Careful assessment and monitoring of the infant following birth are necessary to ensure prompt intervention, referral, and improved outcomes. Additional care, planning, and communication are especially important in the transport environment. PMID- 25136750 TI - Family-centered care during acute neonatal transport. AB - PURPOSE: To evaluate current transport team communication practices and identify areas for improvement from the parents' perspective. We also sought to determine whether parents perceived that they were active participants in the care of their infants during the transport process, consistent with the concepts of providing family-centered care (FCC). SUBJECTS: Purposeful sampling of mothers and fathers (or maternally designated support person if the father was not involved) of 25 infants who were transported for acute care to a level III neonatal intensive care unit (NICU) between October 1, 2012, and September 18, 2013. DESIGN: This quality improvement project used quantitative and qualitative analysis of a parent questionnaire. METHODS: Mothers and fathers (or the support person) of transported infants were invited to complete a questionnaire consisting of yes/no and open-ended questions within the first 2 weeks of their infants' transport to a level III NICU. The questions were related to the communication and information parents received and their ability to participate in the transport process. RESULTS: Twenty-seven parents completed the questionnaire. Responses to yes/no questions identified areas for improvement for the transport team. These included providing parents the opportunity to view an informational video; ensuring that mothers had the opportunity to provide colostrum or breast milk before transport; and providing an explanation to parents about their role as active participants in their infants' care. Responses to the open-ended questions indicated that approximately 40% of parents felt they had received adequate information about their infants' care during the transport and many parents (40%) cited separation from their infants as very concerning and causing distress. More than one-third (40%) of the parents specifically stated that at least 1 parent should accompany the infant during the transport. One father in this sample had been able to accompany his infant to the tertiary center. CONCLUSIONS: The integration of FCC core concepts during an acute neonatal transport is important to parents. The orientation of parents to FCC during the transport process may facilitate communication and help them become active participants in their infants' care. PMID- 25136751 TI - Therapeutic hypothermia on transport: providing safe and effective cooling therapy as the link between birth hospital and the neonatal intensive care unit. AB - Therapeutic hypothermia as a neuroprotective strategy in neonates is an established standard of care for infants with hypoxic-ischemic encephalopathy (HIE) in tertiary care neonatal intensive care units (NICUs). To maximize the neuroprotective effect in infants with HIE, hypothermia is initiated as soon as possible after birth. Many infants who would benefit from therapeutic hypothermia are not born at centers that have intensive care units or offer therapeutic hypothermia and are thus transported to a tertiary care center with a NICU, offering specialty services of therapeutic hypothermia and pediatric neurology. The neonatal transport team plays a significant role in the management of these critically ill infants. Clinical research provides data for safe and effective management of these infants during therapeutic hypothermia in the NICU; however, there are no evidence-based clinical guidelines for management before and during transport. The establishment of evidence-based guidelines for cooling before and during transport will facilitate early recognition of infants who would benefit from therapeutic hypothermia therapy, and decrease delay in initiation of therapy. Careful assessment, monitoring, and intervention by the transport team are critical to provide appropriate care and ensure safe transport of these infants. PMID- 25136752 TI - Managing common neonatal respiratory conditions during transport. AB - As neonatal care in the tertiary setting advances, neonatal transport teams are challenged with incorporating these innovations into their work environment. One of the largest areas of advancement over the last decade involves respiratory support and management. Many major respiratory treatments and the equipment required have been adapted for transport, whereas others are not yet feasible. This article reviews the history of respiratory management during neonatal transport and discusses current methodologies and innovations in transport respiratory management. PMID- 25136754 TI - Bioactive anthraquinone derivatives from the mangrove-derived fungus Stemphylium sp. 33231. AB - Four new anthraquinone derivatives (1-4) and four new alterporriol-type anthranoid dimers (14-17), along with 17 analogues, were isolated from the solid rice fermentation of the fungus Stemphylium sp. 33231 obtained from the mangrove Bruguiera sexangula var. rhynchopetala collected from the South China Sea. Their structures were elucidated using comprehensive spectroscopic methods. The absolute configurations of 1, 3, and 4 were determined by single-crystal X-ray diffraction of their derivatives (1a, 3b, and 4a). The absolute configurations of the chiral 17-19 were determined by comparing their CD spectra with 21. The inhibitory activities of most of the compounds against seven terrestrial pathogenic bacteria and two cancer cell lines were evaluated. PMID- 25136755 TI - Blocked inverted indices for exact clustering of large chemical spaces. AB - The calculation of pairwise compound similarities based on fingerprints is one of the fundamental tasks in chemoinformatics. Methods for efficient calculation of compound similarities are of the utmost importance for various applications like similarity searching or library clustering. With the increasing size of public compound databases, exact clustering of these databases is desirable, but often computationally prohibitively expensive. We present an optimized inverted index algorithm for the calculation of all pairwise similarities on 2D fingerprints of a given data set. In contrast to other algorithms, it neither requires GPU computing nor yields a stochastic approximation of the clustering. The algorithm has been designed to work well with multicore architectures and shows excellent parallel speedup. As an application example of this algorithm, we implemented a deterministic clustering application, which has been designed to decompose virtual libraries comprising tens of millions of compounds in a short time on current hardware. Our results show that our implementation achieves more than 400 million Tanimoto similarity calculations per second on a common desktop CPU. Deterministic clustering of the available chemical space thus can be done on modern multicore machines within a few days. PMID- 25136759 TI - Cyber safety for adolescent girls: bullying, harassment, sexting, pornography, and solicitation. AB - PURPOSE OF REVIEW: To examine cyber safety for adolescent girls, specifically issues around the definition, measurement, prevalence, and impact of cyberbullying, harassment, sexting, pornography, and solicitation. RECENT FINDINGS: Despite some continuing disagreements about definition, especially around cyberbullying and cyber harassment, and about measurement, it is clear that a significant minority of adolescents have potentially or actually harmful experiences on the Internet. There are important sex differences, and those exploited by pornography are mainly women. On some measures, these dangers have increased in recent years, although the extent can be exaggerated. The nature of Internet grooming appears to be changing. Negative effects are well documented in a range of domains, although more longitudinal studies are needed. Individual coping strategies, family and school-based support, and legal actions, all have a role to play in minimizing these dangers. SUMMARY: Cyber safety is an important issue. More research and action is needed, and interventions need to be evaluated for their effectiveness. PMID- 25136758 TI - Addressing the instability of DNA nanostructures in tissue culture. AB - DNA nanotechnology is an advanced technique that could contribute diagnostic, therapeutic, and biomedical research devices to nanomedicine. Although such devices are often developed and demonstrated using in vitro tissue culture models, these conditions may not be compatible with DNA nanostructure integrity and function. The purpose of this study was to characterize the sensitivity of 3D DNA nanostructures produced via the origami method to the in vitro tissue culture environment and identify solutions to prevent loss of nanostructure integrity. We examined whether the physiological cation concentrations of cell culture medium and the nucleases present in fetal bovine serum (FBS) used as a medium supplement result in denaturation and digestion, respectively. DNA nanostructure denaturation due to cation depletion was design- and time-dependent, with one of four tested designs remaining intact after 24 h at 37 degrees C. Adjustment of medium by addition of MgSO4 prevented denaturation. Digestion of nanostructures by FBS nucleases in Mg(2+)-adjusted medium did not appear design-dependent and became significant within 24 h and when medium was supplemented with greater than 5% FBS. We estimated that medium supplemented with 10% FBS contains greater than 256 U/L equivalent of DNase I activity in digestion of DNA nanostructures. Heat inactivation at 75 degrees C and inclusion of actin protein in medium inactivated and inhibited nuclease activity, respectively. We examined the impact of medium adjustments on cell growth, viability, and phenotype. Adjustment of Mg(2+) to 6 mM did not appear to have a detrimental impact on cells. Heat inactivation was found to be incompatible with in vitro tissue culture, whereas inclusion of actin had no observable effect on growth and viability. In two in vitro assays, immune cell activation and nanoparticle endocytosis, we show that using conditions compatible with cell phenotype and nanostructure integrity is critical for obtaining reliable experimental data. Our study thus describes considerations that are vital for researchers undertaking in vitro tissue culture studies with DNA nanostructures and some potential solutions for ensuring that nanostructure integrity and functions are maintained during experiments. PMID- 25136760 TI - Teen pregnancy: an update. AB - PURPOSE OF REVIEW: To provide clinicians with a review of recent research and clinically applicable tools regarding teen pregnancy. RECENT FINDINGS: Teen pregnancy rates have declined but still remain a significant problem in the USA. Teen pregnancy prevention was identified by Centers for Disease Control and Prevention as one of its top six priorities, which is increasing research and intervention data. Long-acting contraceptive methods are acceptable to teens and have been shown to reduce teen birth rates. Pregnant teens need special attention to counseling on pregnancy options and reducing risk during pregnancy with regular prenatal care. Postpartum teens should be encouraged and supported to breastfeed, monitored for depression, and have access to reliable contraception to avoid repeat undesired pregnancy. SUMMARY: This review highlights important issues for all providers caring for female adolescents and those who may encounter teen pregnancy. Foremost prevention of teen pregnancy by comprehensive sexual education and access to contraception is the priority. Educating patients and healthcare providers about safety and efficacy of long-acting reversible contraception is a good step to reducing undesired teen pregnancies. Rates of postpartum depression are greater in adolescents than in adults, and adolescent mothers need to be screened and monitored for depression. Strategies to avoid another undesired pregnancy shortly after delivery should be implemented. PMID- 25136761 TI - Role of apical support defect: correction in women undergoing vaginal prolapse surgery. AB - PURPOSE OF REVIEW: The aim was to review most recent literature and provide updates in clinical management and surgical treatment of apical pelvic organ prolapse. RECENT FINDINGS: In patients who decline surgical intervention, formal referral to pelvic floor muscle training is beneficial over self-directed Kegel exercises. Systematic reviews revealed that sacrocolpopexy has better long-term outcomes than vaginal approaches. Uterosacral ligament suspension and sacrospinous ligament suspension have equal efficacy at 1 year. These procedures should be considered as acceptable alternatives to sacrocolpopexy. Two randomized controlled trials have demonstrated equal efficacy between robotic and laparoscopic sacrocolpopexy. SUMMARY: Minimally invasive sacrocolpopexy should be considered the gold standard for apical prolapse, but these techniques are associated with longer operating times and higher complication rates and longer convalescence than nonmesh vaginal surgery. Surgeons must individualize surgical technique for each patient and should consider a vaginal approach in patients who do not desire laparotomy and are not candidates for minimally invasive surgery. PMID- 25136762 TI - Patient perspective in health technology assessment of pharmaceuticals in Finland. AB - OBJECTIVES: The need to consider the patient perspective in health technology assessments (HTA) has been widely recognized. In July 2012, the Finnish Medicines Agency (Fimea) published a national recommendation for integrating the patient perspective into the HTAs of pharmaceuticals. The aim of this study is to describe the development of the recommendation for integrating the patient perspective into the HTA process of pharmaceuticals in Finland. METHODS: The development of the recommendation was based on a review of international recommendations and experiences of patient and public involvement in HTA. The draft recommendation was tested in two focus group discussions (n = 7 patients) and three individual interviews among diabetes patients (type 1 or 2) using long acting insulin treatment. The recommendation was open for public consultation in April 2012 and revised according to the comments received. RESULTS: Patients will be involved in multiple stages of Fimea's HTA process. The recommendation includes step-by-step instructions on how to assess the patient perspective. The main focus is on qualitative interviews, which will be conducted at the beginning of the assessments to gain information, particularly on patient preferences and values, including positive and negative outcomes important to patients and ethical and social aspects of the medicine's use. CONCLUSIONS: The recommendation will act as a tool to integrate patients' experiences, needs and preferences into Fimea's HTAs of pharmaceuticals. PMID- 25136763 TI - Anti-inflammatory effects of wild Irish mushroom extracts in RAW264.7 mouse macrophage cells. AB - Mushrooms and mushroom extracts have traditionally been used as therapies for a wide variety of ailments, including allergy, arthritis, and other inflammatory disorders. However, more evidence is required on the mechanism by which mushrooms exert these effects. In the present study, the anti-inflammatory properties of ethanol and hot water extracts prepared from 27 fungal samples collected between October and November 2011 at various forest locations in the southwest of Ireland were investigated using the lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7 cells) model of inflammation. LPS-stimulated cells were incubated in the presence of mushroom extracts at nontoxic concentrations for 24 h and the production of interleukin-6 (IL-6) was quantified by ELISA. Seven ethanolic and one hot water extract that decreased IL-6 production were selected for further study. The extracts were then incubated with LPS-stimulated cells for 24 h and the production of IL-6, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) was measured. Ethanolic extracts prepared from Russula mairei, Lactarius blennius, Craterellus tubaeformis, Russula fellea, and Craterellus cornucopioides demonstrated selective anti-inflammatory activity by decreasing the production of NO and IL-6 but not TNF-alpha in LPS-stimulated RAW264.7 cells. These findings support existing evidence of the anti-inflammatory potential of mushroom extracts. PMID- 25136764 TI - Nanoscale metal-organic frameworks for real-time intracellular pH sensing in live cells. AB - Real-time measurement of intracellular pH in live cells is of great importance for understanding physiological/pathological processes and developing intracellular drug delivery systems. We report here the first use of nanoscale metal-organic frameworks (NMOFs) for intracellular pH sensing in live cells. Fluorescein isothiocyanate (FITC) was covalently conjugated to a UiO NMOF to afford F-UiO NMOFs with exceptionally high FITC loadings, efficient fluorescence, and excellent ratiometric pH-sensing properties. Upon rapid and efficient endocytosis, F-UiO remained structurally intact inside endosomes. Live cell imaging studies revealed endo- and exocytosis of F-UiO and endosome acidification in real time. Fluorescently labeled NMOFs thus represent a new class of nanosensors for intracellular pH sensing and provide an excellent tool for studying NMOF-cell interactions. PMID- 25136766 TI - Effects of the steric hindrance of micropores in the hyper-cross-linked polymeric adsorbent on the adsorption of p-nitroaniline in aqueous solution. AB - A hyper-cross-linked polymeric adsorbent with "--CH2--phenol--CH2--" as the cross linked bridge (denoted GQ-05), and another hyper-cross-linked polymeric adsorbent with "--CH2--p-cresol--CH2--" as the cross-linked bridge (denoted GQ-03) were synthesized to reveal the effect of the steric hindrance of micropores in the hyper-cross-linked polymeric adsorbent on adsorption capacity and adsorption rate of p-nitroaniline (PNA) from aqueous solution. The results of adsorption kinetics indicated the order of the adsorption rate GQ-05>GQ-03. The pseudo-first-order rate equation could describe the entire adsorption process of PNA onto GQ-05 while the equation characterized the adsorption process of GQ-03 in two stages. The order of the adsorption capacity GQ-05>GQ-03 was demonstrated by thermodynamic analysis and dynamic adsorption. The steric hindrance of micropores in the hyper-cross-linked polymeric adsorbent was a crucial factor for the order of the adsorption capacity and adsorption rate. PMID- 25136765 TI - On the possible role of macrofungi in the biogeochemical fate of uranium in polluted forest soils. AB - Interactions of macrofungi with U, Th, Pb and Ag were investigated in the former ore mining district of Pribram, Czech Republic. Samples of saprotrophic (34 samples, 24 species) and ectomycorrhizal (38 samples, 26 species) macrofungi were collected from a U-polluted Norway spruce plantation and tailings and analyzed for metal content. In contrast to Ag, which was highly accumulated in fruit bodies, concentrations of U generally did not exceed 3mg/kg which indicates a very low uptake rate and efficient exclusion of U from macrofungi. In ectomycorrhizal tips (mostly determined to species level by DNA sequencing), U contents were practically identical with those of the non-mycorrhizal fine spruce roots. These findings suggest a very limited role of macrofungi in uptake and biotransformation of U in polluted forest soils. Furthermore, accumulation of U, Th, Pb and Ag in macrofungal fruit-bodies apparently does not depend on total content and chemical fractionation of these metals in soils (tested by the BCR sequential extraction in this study). PMID- 25136767 TI - A sweet new wave: structures and mechanisms of enzymes that digest polysaccharides from marine algae. AB - Marine algae contribute approximately half of the global primary production. The large amounts of polysaccharides synthesized by these algae are degraded and consumed by microbes that utilize carbohydrate-active enzymes (CAZymes), thus creating one of the largest and most dynamic components of the Earth's carbon cycle. Over the last decade, structural and functional characterizations of marine CAZymes have revealed a diverse set of scaffolds and mechanisms that are used to degrade agars, carrageenan, alginate and ulvan-polysaccharides from red, brown and green seaweeds, respectively. The analysis of these CAZymes is not only expanding our understanding of their functions but is enabling the enhanced annotation of (meta)-genomic data sets, thus promoting an improved understanding of microbes that drive this marine component of the carbon cycle. Furthermore, this information is setting a foundation that will enable marine algae to be harnessed as a novel resource for biorefineries. In this review, we cover the most recent structural and functional analyses of marine CAZymes that are specialized in the digestion of macro-algal polysaccharides. PMID- 25136768 TI - Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro. AB - Paclitaxel (PT)-induced neurotoxicity is a significant problem associated with successful treatment of cancers. Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. Whether IGF-1 has protective effects on neurite growth, cell viability, neuronal apoptosis and neuronal phenotypes in DRG neurons with PT-induced neurotoxicity is still unclear. In this study, primary cultured rat DRG neurons were used to assess the effects of IGF-1 on DRG neurons with PT-induced neurotoxicity. The results showed that PT exposure caused neurite retraction in a dose-dependent manner. PT exposure caused a decrease of cell viability and an increase in the ratio of apoptotic cells which could be reversed by IGF-1. The percentage of calcitonin gene-related peptide immunoreactive (CGRP IR) neurons and neurofilament (NF)-200-IR neurons, mRNA, and protein levels of CGRP and NF-200 decreased significantly after treatment with PT. IGF-1 administration had protective effects on CGRP-IR neurons, but not on NF-200-IR neurons. Either extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 or phosphatidylinositol 3-kinase (PI3 K) inhibitor LY294002 blocked the effect of IGF-1. The results imply that IGF-1 may attenuate apoptosis to improve neuronal cell viability and promote neurite growth of DRG neurons with PT-induced neurotoxicity. Moreover, these results support an important neuroprotective role of exogenous IGF-1 on distinct subpopulations of DRG neurons which is responsible for skin sensation. The effects of IGF-1 might be through ERK1/2 or PI3 K/Akt signaling pathways. These findings provide experimental evidence for IGF-1 administration to alleviate neurotoxicity of distinct subpopulations of DRG neurons induced by PT. PMID- 25136770 TI - Early response to chemoradiotherapy for nasopharyngeal carcinoma treatment: Value of dynamic contrast-enhanced 3.0 T MRI. AB - PURPOSE: To prospectively evaluate the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) value for predicting early nasopharyngeal carcinoma (NPC) chemoradiotherapy (CRT) response. MATERIALS AND METHODS: Forty-two patients with advanced NPC were recruited and received three DCE-MRI exams before treatment (Pre-Tx), as well as 3 days (Day 3-Tx) and 40 days (Day 40-Tx) after chemotherapy initiation (two neoadjuvant chemotherapy cycles, NAC). We used DCE Tool to measure primary tumor kinetic parameters (K(trans) , Kep , ve , and vp ) using the extended Tofts model. Kinetic parameters and corresponding changes were compared between responders and nonresponders after NAC or CRT treatment using Student's t or Mann-Whitney U tests. RESULTS: Response to two NAC cycles correlated with short-term local control (P = 0.01). Compared to the nonresponder group, the responder group presented with significantly larger DeltaK(trans) (0 3) , DeltaKep(0-3) , and Deltavp(0-3) values after NAC (P < 0.05). The complete response group after CRT exhibited significantly lower K(trans) (Day 40-Tx) and larger DeltaK(trans) (0-3) values than the residual group (P = 0.05). High sensitivity (range: 74.1%-90%) and moderate-to-high specificity (range: 50% 84.3%) distinguished nonresponders from responders grouping after NAC or CRT, with diagnostic efficiency ranging from 69.3%-88%. CONCLUSION: Our study showed kinetic parameter changes earlier after chemotherapy were potential markers for NPC patients receiving CRT therapy following NAC. PMID- 25136771 TI - Biological risk among hospital housekeepers. AB - Although not directly responsible for patient care, hospital housekeepers are still susceptible to accidents with biological material. The objectives of this study were to establish profile and frequency of accidents among hospital housekeepers, describe behaviors pre- and postaccident, and risk factors. This was a cross-sectional study with hospital housekeepers in Goiania, Brazil. Data were obtained from interviews and vaccination records. The observations were as follows: (1) participating workers: 94.3%; (2) incomplete hepatitis B vaccination: 1 in 3; and (3) accident rate: 26.5%, mostly percutaneous with hypodermic needles, and involved blood from an unknown source; roughly half occurred during waste management. Upon review, length of service less than 5 years, completed hepatitis B vaccination, and had been tested for anti-HBs (hepatitis B surface antigen) influenced frequency of accidents. These findings suggest that improper disposal of waste appears to enhance the risk to hospital housekeepers. All hospital workers should receive continued training with regard to waste management. PMID- 25136769 TI - Synthesis and characterization of oligonucleotides containing a nitrogen mustard formamidopyrimidine monoadduct of deoxyguanosine. AB - N(5)-Substituted formamidopyrimidine adducts have been observed from the reaction of dGuo or DNA with aziridine containing electrophiles, including nitrogen mustards. However, the role of substituted Fapy-dGuo adducts in the biological response to nitrogen mustards and related species has not been extensively explored. We have developed chemistry for the site-specific synthesis of oligonucleotides containing an N(5)-nitrogen mustard Fapy-dGuo using the phosphoramidite approach. The lesion was found to be a good substrate for Escherichia coli endonuclease IV and formamidopyrimidine glycosylase. PMID- 25136772 TI - Structural and mutational analysis of a monomeric and dimeric form of a single domain antibody with implications for protein misfolding. AB - Camelid single domain antibodies (sdAb) are known for their thermal stability and reversible refolding. We have characterized an unusually stable sdAb recognizing Staphylococcal enterotoxin B with one of the highest reported melting temperatures (T(m) = 85 degrees C). Unexpectedly, ~10-20% of the protein formed a dimer in solution. Three other cases where <20% of the sdAb dimerized have been reported; however, this is the first report of both the monomeric and dimeric X ray crystal structures. Concentration of the monomer did not lead to the formation of new dimer suggesting a stable conformationally distinct species in a fraction of the cytoplasmically expressed protein. Comparison of periplasmic and cytoplasmic expression showed that the dimer was associated with cytoplasmic expression. The disulfide bond was partially reduced in the WT protein purified from the cytoplasm and the protein irreversibly unfolded. Periplasmic expression produced monomeric protein with a fully formed disulfide bond and mostly reversible refolding. Crystallization of a disulfide-bond free variant, C22A/C99V, purified from the periplasm yielded a structure of a monomeric form, while crystallization of C22A/C99V from the cytoplasm produced an asymmetric dimer. In the dimer, a significant conformational asymmetry was found in the loop residues of the edge beta-strands (S50-Y60) containing the highly variable complementarity determining region, CDR2. Two dimeric assemblies were predicted from the crystal packing. Mutation of a residue at one of the interfaces, Y98A, disrupted the dimer in solution. The pleomorphic homodimer may yield insight into the stability of misfolded states and the importance of the conserved disulfide bond in preventing their formation. PMID- 25136774 TI - Inpatient and emergency service utilization in patients with idiopathic intracranial hypertension. AB - BACKGROUND: Many patients with idiopathic intracranial hypertension (IIH) are diagnosed in the emergency department (ED) or visit the ED during the course of their illness. We studied the use of inpatient and emergency services, determined what procedures and tests were provided at those encounters, evaluated how these variables changed over the study period and examined the coding validity of the International Classification of Diseases (ICD)-9 code for IIH (348.2) for adult patients seen in our affiliated EDs and inpatient services. METHODS: Retrospective review of medical records over a 11-year period (2000-2011). RESULTS: We were able to analyze 137 encounters from 51 patients. Sixty-eight percent of encounters were to the ED and 40% of those patients were subsequently admitted to the hospital. The most common symptoms were headaches (96%), vision change (53%), and photophobia (27%). Recurrent symptoms accounted for 43% of encounters, followed by surgical complications (26%) and initial presentation (12%). Four patients (25% of the patients who received a diagnosis in the ED) were misdiagnosed at their initial presentation and correctly diagnosed on a subsequent ED visit. The number of ED visits more than doubled over the study period. The ICD-9 code had a low positive predictive value (55%) for identifying patients with IIH. CONCLUSIONS: The ED was commonly used by patients with IIH, with a mean of 2.7 visits per patient. The rate of a missed diagnosis was similar to another published series and is concerning for potentially permanent visual loss in undiagnosed patients. In our experience, the ICD-9 code vastly overestimated the number of ED and inpatient encounters attributable to IIH. This has important implications for research studies, particularly those relying on national inpatient databases. PMID- 25136775 TI - Idiopathic opticochiasmatic arachnoiditis. AB - : A critical review of the literature indicates that idiopathic opticochiasmatic arachnoiditis, once considered an important consideration in patients with otherwise unexplained optic atrophy, is not a valid disease entity. PMID- 25136773 TI - Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial Ishikawa cells. AB - BACKGROUND: The link between environmental estrogen exposure and defects in the female reproductive tract is well established. The phytoestrogen genistein is able to modulate uterine estrogen receptor (ER) activity, and dietary exposure is associated with uterine pathologies. Regulation of stress and immune functions by the glucocorticoid receptor (GR) is also an integral part of maintaining reproductive tract function; disruption of GR signaling by genistein may also have a role in the adverse effects of genistein. OBJECTIVE: We evaluated the transcriptional response to genistein in Ishikawa cells and investigated the effects of genistein on GR-mediated target genes. METHODS: We used Ishikawa cells as a model system to identify novel targets of genistein and the synthetic glucocorticoid dexamethasone through whole genome microarray analysis. Common gene targets were defined and response patterns verified by quantitative real time reverse-transcription polymerase chain reaction. The mechanism of transcriptional antagonism was determined for select genes. RESULTS: Genistein regulated numerous genes in Ishikawa cells independently of estradiol, and the response to coadministration of genistein and dexamethasone was unique compared with the response to either estradiol or dexamethasone alone. Furthermore, genistein altered glucocorticoid regulation of GR target genes. In a select set of genes, co-regulation by dexamethasone and genistein was found to require both GR and ERalpha signaling, respectively. CONCLUSIONS: Using Ishikawa cells, we observed that exposure to genistein resulted in distinct changes in gene expression and unique differences in the GR transcriptome. PMID- 25136776 TI - Sorafenib regulating ERK signals pathway in gastric cancer cell. AB - The involvement of ERK signals in gastric carcinoma was investigated using Western blot, MTT, and flow cytometric analysis in cultured cells SGC7901. Results showed that treatment of sorafenib potently inhibited gastric SGC7901 cells proliferation, migration, invasion as well as promoted apoptosis. Treatment of sorafenib significantly decreased phosphorylation activation of ERK protein in a dose-dependent manner. Treatment of sorafenib still significantly increased caspase-3, bax, cyt-c protein expression and decreased bcl-2 protein in a dose dependent manner. Our study confirms that ERK signals pathway is closely associated with development of gastric cancer. Deactivation of phosphorylation of ERK protein is one of the mechanisms of sorafenib inhibiting gastric cancer. PMID- 25136777 TI - Integrated biomarker responses in zebrafish exposed to sulfonamides. AB - Dispersed pharmaceuticals such as sulfonamides pose a threat to aquatic ecosystems. We evaluated potential biomarkers of sulfonamide exposure using an extended zebrafish (Danio rerio) toxicity test. The tested sulfonamides induced obvious effects on spontaneous swimming activity and heartbeat rate in zebrafish. Glutathione S-transferase (GST) and malondialdehyde (MDA) were examined to reflect the biomarker response of zebrafish exposed to three sulfonamides (sulfamethoxazole, sulfadiazine (SDZ) and sulfadimidine). Both GST and MDA showed time-dependent responses to sulfonamide exposure. GST activity was significantly increased after exposure to sulfonamides for 3 days, while MDA concentration reached a maximum during the first day and then declined. These results suggest that MDA may be a more sensitive biomarker of sulfonamide toxicity than GST. These investigations demonstrated that SDZ was a typical inducer of metabolic enzymes, suggesting that it poses a potential ecotoxicological risk to aquatic ecosystems. PMID- 25136778 TI - Endothelium-dependent and -independent vasorelaxant actions and mechanisms induced by total flavonoids of Elsholtzia splendens in rat aortas. AB - Elsholtzia splendens (ES) is, rich in flavonoids, used to repair copper contaminated soil in China, which has been reported to benefit cardiovascular systems as folk medicine. However, few direct evidences have been found to clarify the vasorelaxation effect of total flavonoids of ES (TFES). The vasoactive effect of TFES and its underlying mechanisms in rat thoracic aortas were investigated using the organ bath system. TFES (5-200mg/L) caused a concentration-dependent vasorelaxation in endothelium-intact rings, which was not abolished but significantly reduced by the removal of endothelium. The nitric oxide synthase (NOS) inhibitor N(omega)-nitro-l-arginine methyl ester (100MUM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,2-alpha]quinoxalin-1 one (30MUM) significantly blocked the endothelium-dependent vasorelaxation of TFES. Meanwhile, NOS activity in endothelium-intact aortas was concentration dependently elevated by TFES. However, indomethacin (10MUM) did not affect TFES induced vasorelaxation. Endothelium-independent vasorelaxation of TFES was significantly attenuated by KATP channel blocker glibenclamide. The accumulative Ca(2+)-induced contraction in endothelium-denuded aortic rings primed with KCl or phenylephrine was markedly weakened by TFES. These results revealed that the NOS/NO/cGMP pathway is likely involved in the endothelium-dependent vasorelaxation induced by TFES, while activating KATP channel, inhibiting intracellular Ca(2+) release, blocking Ca(2+) channels and decreasing Ca(2+) influx into vascular smooth muscle cells might contribute to the endothelium independent vasorelaxation conferred by TFES. PMID- 25136779 TI - All-trans-retinoid acid (ATRA) suppresses chondrogenesis of rat primary hind limb bud mesenchymal cells by downregulating p63 and cartilage-specific molecules. AB - P63 null mice have no or truncated limbs and mutations in human p63 cause several skeletal syndromes that also show limb and digit abnormalities, suggesting its essential role in bone development. In the current study, we investigated the effect of ATRA on chondrogenesis using mesenchymal cells from rat hind limb bud and further examined the mRNA and protein expression of Sox9 and Col2a1 and p63 in rat hind limb bud cells. Limb buds were isolated from embryos from euthanized female rats. Growth of hind limb bud mesenchymal cells was determined by the 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assays. Formation of cartilage nodules was examined by Alcian blue-nuclear fast red staining. The expression of Sox9, Col2al and p63 was determined by Real-time RT-PCR and immunoblotting assays, respectively. Our MTT assays revealed that ATRA at 1 and 10MUM significantly suppressed the growth of mesenchymal cells from rat hind limb bud at 24 and 48h (P<0.01 vs. controls). Alcian blue staining further showed that ATRA caused a significant dose-dependent reduction in the area of cartilage nodules (P<0.05 in all vs. controls). At 1MUM ATRA, the area of cartilage nodules from hind limb bud cells was reduced to 0.05+/-0.03mm from 0.15+/-0.01mm in controls. Real-time RT-PCR assays further indicated that 1 and 10MUM ATRA markedly reduced the mRNA expression of Sox9, Col2al and p63 in hind limb bud cells (P<0.05 in all vs. controls). In addition, ATRA time-dependently inhibits the mRNA expression of p63, Sox9 and Col2al. Western blotting assays additionally showed that ATRA dose-dependently reduced the expression of Sox9, Col2al and p63 (P<0.05 in all vs. controls). Together, our results suggest that ATRA suppresses chondrogenesis by modulating the expression of Sox9, Col2al and p63 in primary hind limb bud mesenchymal cells. PMID- 25136780 TI - Macrophage-derived chemokine (CCL22) is a novel mediator of lung inflammation following hemorrhage and resuscitation. AB - Resuscitation of patients after hemorrhage often results in pulmonary inflammation and places them at risk for the development of acute respiratory distress syndrome. Our previous data indicate that macrophage-derived chemokine (MDC/CCL22) is elevated after resuscitation, but its direct role in this inflammatory response is unknown. Macrophage-derived chemokine signaling through the C-C chemokine receptor type 4 (CCR4) is implicated in other pulmonary proinflammatory conditions, leading us to hypothesize that MDC may also play a role in the pathogenesis of lung inflammation following hemorrhage and resuscitation. To test this, C57BL/6 mice underwent pressure-controlled hemorrhage followed by resuscitation with lactated Ringer's solution. Pulmonary inflammation and inflammatory cell recruitment were analyzed with histological staining, and serum- and tissue-level cytokines were measured by enzyme-linked immunosorbent assay. Pulmonary inflammation and cell recruitment following hemorrhage and resuscitation were associated with systemic MDC levels. Inhibition of MDC via injection of a specific neutralizing antibody prior to hemorrhage and resuscitation significantly reduced pulmonary levels of the chemotactic cytokines keratinocyte-derived chemokine and macrophage inflammatory proteins 2 and 1alpha, as well as inflammatory cell recruitment to the lungs. Intravenous administration of recombinant MDC prior to resuscitation augmented pulmonary inflammation and cell recruitment. Histological evaluation revealed the expression of CCR4 within the bronchial epithelium, and in vitro treatment of activated bronchial epithelial cells with MDC resulted in production and secretion of neutrophil chemokines. The present study identifies MDC as a novel mediator of lung inflammation after hemorrhage and resuscitation. Macrophage-derived chemokine neutralization may provide a therapeutic strategy to mitigate this inflammatory response. PMID- 25136783 TI - Screening for hyperuricaemia and gout: a perspective and research agenda. AB - The goal of a screening programme is to reduce an adverse health outcome in a defined population. Screening can be undertaken at several stages throughout the disease course: before the onset of disease, early in the course of the disease, or in established disease (for complications). In the setting of asymptomatic hyperuricaemia and gout, the aim of screening would be to identify those individuals with hyperuricaemia and therefore at risk of gout, with the aim of introducing interventions to prevent the onset of gout. Herein we consider the concepts of screening for hyperuricaemia and gout, potential screening methods, and target populations that might benefit from such an approach. PMID- 25136782 TI - Paraneoplastic syndromes in rheumatology. AB - For patients that present with musculoskeletal symptoms, diagnostic procedures carried out by physicians and rheumatologists are primarily aimed at confirming or excluding the occurrence of primary rheumatic diseases. Another important trigger for musculoskeletal disease, however, is the presence of a tumour. Careful clinical investigation and knowledge of the gestalt of musculoskeletal syndromes related to respective tumour entities is of utmost importance for the diagnosis of paraneoplastic rheumatic diseases such as hypertrophic osteoarthropathy, paraneoplastic polyarthritis, RS3PE syndrome, palmar fasciitis and polyarthritis, cancer-associated myositis and tumour-induced osteomalacia. This places great responsibility on rheumatologists in diagnosing malignancies and referring the patient for effective treatment. The selective influence of tumours on musculoskeletal tissue is surprising and indicates that tumours alter tissues such as the periosteum, synovial membrane, subcutaneous connective tissue, fascia, muscles and bones by specific molecular processes. Some of the underlying mechanisms have been unravelled, providing valuable information on the physiologic and pathophysiologic roles of mediators such as vascular endothelial growth factor and fibroblast growth factor 23. PMID- 25136781 TI - Transforming growth factor beta--at the centre of systemic sclerosis. AB - Transforming growth factor beta (TGF-beta) has long been implicated in fibrotic diseases, including the multisystem fibrotic disease systemic sclerosis (SSc). Expression of TGF-beta-regulated genes in fibrotic skin and lungs of patients with SSc correlates with disease activity, which points to this cytokine as the central mediator of pathogenesis. Patients with SSc often develop pulmonary arterial hypertension (PAH), a particularly lethal complication caused by vascular dysfunction. Several genetic diseases with vascular features related to SSc, such as familial PAH and hereditary haemorrhagic telangiectasia, are caused by mutations in the TGF-beta-sensing ALK-1 signalling pathway. These observations suggest that increased TGF-beta signalling causes both vascular and fibrotic features of SSc. The question of how latent TGF-beta becomes activated in local SSc tissues is, therefore, central to the understanding of SSc. Both TGF-beta1 and TGF-beta3 can be activated by integrins alphavbeta6 and alphavbeta8, whose upregulation in bronchial epithelial cells can activate TGF-beta in SSc lungs. Other alphav integrins, thrombospondin-1 or altered TGF-beta sequestration by matrix proteins might be important in other target tissues. How the immune system triggers this process remains unclear, although links between inflammation and TGF-beta activation are emerging. Together, these observations provide an increasingly secure framework for understanding TGF-beta in SSc pathogenesis. PMID- 25136784 TI - IL-6 biology: implications for clinical targeting in rheumatic disease. AB - IL-6 has been linked to numerous diseases associated with inflammation, including rheumatoid arthritis, inflammatory bowel disease, vasculitis and several types of cancer. Moreover, IL-6 is important in the induction of hepatic acute-phase proteins for the trafficking of acute and chronic inflammatory cells, the differentiation of adaptive T-cell responses, and tissue regeneration and homeostatic regulation. Studies have investigated IL-6 biology using cell-bound IL-6 receptors expressed predominantly on hepatocytes and certain haematopoietic cells versus activation mediated by IL-6 and soluble IL-6 receptors via a second protein, gp130, which is expressed throughout the body. Advances in this research elucidating the differential effects of IL-6 activation provide important insights into the role of IL-6 in health and disease, as well as its potential as a therapeutic target. Knowledge of the basic biology of IL-6 and its signalling pathways can better inform both the research agenda for IL-6-based targeted therapies as well as the clinical use of strategies affecting IL-6-mediated inflammation. This Review covers novel, emerging aspects of the biology of IL-6, which might lead to more specific blockade of IL-6 signalling without compromising the protective function of this cytokine in the body's defence against infections. PMID- 25136787 TI - A simplified coulometric method for multi-sample measurements of total dissolved inorganic carbon concentration in marine waters. AB - A new system requiring greatly reduced operator intervention has been developed for the determination of dissolved inorganic carbon concentration in marine waters. Based on a coulometric method, the system has an accuracy and precision comparable to more complex and expensive methods currently employed. A syringe pump equipped with a 12-port distribution valve is used to precisely dispense an acid solution and sample into a gas stripper. The system can autonomously measure eight discrete samples in duplicate or triplicate with no operator input. The best precision (%RSD) obtained was 0.022% (n = 14) or less than +/-1.0 MUmol kg( 1). The system is calibrated against a certified reference material (CRM). Average offset from the CRM was 1.2 MUmol kg(-1). Sample throughput was 4 samples per h. Carryover effects are negligible but field sample analyses suggest that prefiltering may be necessary in highly turbid waters. PMID- 25136786 TI - The role of genetics and epigenetics in the pathogenesis of systemic sclerosis. AB - Systemic sclerosis (SSc) is a complex autoimmune disease of unclear aetiology. A multitude of genetic studies, ranging from candidate-gene studies to genome-wide association studies, have identified a large number of genetic susceptibility factors for SSc and its clinical phenotypes, but the contribution of these factors to disease susceptibility is only modest. However, in an endeavour to explore how the environment might affect genetic susceptibility, epigenetic research into SSc is rapidly expanding. Orchestrated by environmental factors, epigenetic modifications can drive genetically predisposed individuals to develop autoimmunity, and are thought to represent the crossroads between the environment and genetics in SSc. Therefore, in addition to providing a comprehensive description of the current understanding of genetic susceptibility underlying SSc, this Review describes the involvement of epigenetic phenomena, including DNA methylation patterns, histone modifications and microRNAs, in SSc. PMID- 25136785 TI - Improving cardiovascular and renal outcomes in gout: what should we target? AB - Epidemiological and experimental studies have shown that hyperuricaemia and gout are intricately linked with hypertension, metabolic syndrome, chronic kidney disease and cardiovascular disease. A number of studies suggest that hyperuricaemia and gout are independent risk factors for the development of these conditions and that these conditions account, in part, for the increased mortality rate of patients with gout. In this Review, we first discuss the links between hyperuricaemia, gout and these comorbidities, and present the mechanisms by which uric acid production and gout might favour the development of cardiovascular and renal diseases. We then emphasize the potential benefit of urate-lowering therapies on cardiovascular and renal outcomes in patients with hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout with these comorbidities seem to be multifactorial, implicating low-grade systemic inflammation and xanthine oxidase (XO) activity, as well as the deleterious effects of hyperuricaemia itself. Patients with asymptomatic hyperuricaemia should be treated by nonpharmacological means to lower their SUA levels. In patients with gout, long-term pharmacological inhibition of XO is a treatment strategy that might also reduce cardiovascular and renal comorbidities, because of its dual effect of lowering SUA levels as well as reducing free radical production during uric acid formation. PMID- 25136788 TI - L. monocytogenes in a cheese processing facility: Learning from contamination scenarios over three years of sampling. AB - The aim of this study was to analyze the changing patterns of Listeria monocytogenes contamination in a cheese processing facility manufacturing a wide range of ready-to-eat products. Characterization of L. monocytogenes isolates included genotyping by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Disinfectant-susceptibility tests and the assessment of L. monocytogenes survival in fresh cheese were also conducted. During the sampling period between 2010 and 2013, a total of 1284 environmental samples were investigated. Overall occurrence rates of Listeria spp. and L. monocytogenes were 21.9% and 19.5%, respectively. Identical L. monocytogenes genotypes were found in the food processing environment (FPE), raw materials and in products. Interventions after the sampling events changed contamination scenarios substantially. The high diversity of globally, widely distributed L. monocytogenes genotypes was reduced by identifying the major sources of contamination. Although susceptible to a broad range of disinfectants and cleaners, one dominant L. monocytogenes sequence type (ST) 5 could not be eradicated from drains and floors. Significantly, intense humidity and steam could be observed in all rooms and water residues were visible on floors due to increased cleaning strategies. This could explain the high L. monocytogenes contamination of the FPE (drains, shoes and floors) throughout the study (15.8%). The outcome of a challenge experiment in fresh cheese showed that L. monocytogenes could survive after 14days of storage at insufficient cooling temperatures (8 and 16 degrees C). All efforts to reduce L. monocytogenes environmental contamination eventually led to a transition from dynamic to stable contamination scenarios. Consequently, implementation of systematic environmental monitoring via in-house systems should either aim for total avoidance of FPE colonization, or emphasize a first reduction of L. monocytogenes to sites where contamination of the processed product is unlikely. Drying of surfaces after cleaning is highly recommended to facilitate the L. monocytogenes eradication. PMID- 25136789 TI - The influence of subminimal inhibitory concentrations of benzalkonium chloride on biofilm formation by Listeria monocytogenes. AB - Disinfectants, such as benzalkonium chloride (BAC), are commonly used to control Listeria monocytogenes and other pathogens in food processing plants. Prior studies have demonstrated that the resistance to BAC of L. monocytogenes was associated with the prolonged survival of three strains of molecular serotype 1/2a in an Iberian pork processing plant. Because survival in such environments is related to biofilm formation, we hypothesised that the influence of BAC on the biofilm formation potential of L. monocytogenes might differ between BAC resistant strains (BAC-R, MIC>=10mg/L) and BAC-sensitive strains (BAC-S, MIC<=2.5mg/L). To evaluate this possibility, three BAC-R strains and eight BAC-S strains, which represented all of the molecular serotype 1/2a strains detected in the sampled plant, were compared. Biofilm production was measured using the crystal violet staining method in 96-well microtitre plates. The BAC-R strains produced significantly (p<0.05) less biofilm than the BAC-S in the absence of BAC, independent of the rate of planktonic growth. In contrast, when the biofilm values were measured in the presence of BAC, one BAC-R strain (S10-1) was able to form biofilm at 5mg/L of BAC, which prevented biofilm formation among the rest of the strains. A genetic determinant of BAC resistance recently described in L. monocytogenes (Tn6188) was detected in S10-1. When a BAC-S strain and its spontaneous mutant BAC-R derivative were compared, resistance to BAC led to biofilm formation at 5mg/L of BAC and to a significant (p<0.05) stimulation of biofilm formation at 1.25mg/L of BAC, which significantly (p<0.05) reduced the biofilm level in the parent BAC-S strain. Our results suggest that the effect of subminimal inhibitory concentrations of BAC on biofilm production by L. monocytogenes might differ between strains with different MICs and even between resistant strains with similar MICs but different genetic determinants of BAC resistance. For BAC-R strains similar to S10-1, subminimal inhibitory BAC may represent an advantage, compensating for the weak biofilm formation level that might be associated with resistance. Biofilm formation in the presence of increased subminimal inhibitory concentrations of the disinfectant may represent an important attribute among certain resistant and persistent strains of L. monocytogenes. PMID- 25136790 TI - Tonic water-induced generalized bullous fixed eruption. PMID- 25136792 TI - Low carrier density epitaxial graphene devices on SiC. AB - The transport characteristics of graphene devices with low n- or p-type carrier density (~10(10) -10(11) cm(-2) ), fabricated using a new process that results in minimal organic surface residues, are reported. The p-type molecular doping responsible for the low carrier densities is initiated by aqua regia. The resulting devices exhibit highly developed nu = 2 quantized Hall resistance plateaus at magnetic field strengths of less than 4 T. PMID- 25136791 TI - Rationale and study design of the REM-HF study: remote management of heart failure using implanted devices and formalized follow-up procedures. AB - AIMS: We wish to assess the clinical and cost-effectiveness of remote monitoring of heart failure patients with cardiac implanted electronic devices. METHODS: REM HF is a multicentre, randomized, non-blinded, parallel trial designed to compare weekly remote monitoring-driven management with usual care for patients with cardiac implanted electronic devices (ICD, CRT-D, or CRT-P). The trial is event driven, and the final analysis will be performed when 546 events have been observed or the study is terminated at the interim analysis. We have randomized 1650 patients to be followed up for a minimum of 2 years. Patients will remain in the trial up to study termination. The first patient was randomized in September 2011 and the study is expected to complete in early 2016. The primary combined endpoint is time to first event of all-cause death or unplanned hospitalization for cardiovascular reasons. An economic evaluation will be performed, estimating the cost per quality-adjusted life year, with direct costs estimated from the National Health Service perspective and quality of life assessed by the EQ-5D, Short-Form 12, and Kansas City Cardiomyopathy Questionnaires. The study design has been informed by a feasibility study. CONCLUSION: REM-HF is a multicentre randomized study that will provide important data on the effect of remote monitoring-driven management of implanted cardiac devices on morbidity and mortality, as well as the cost-effectiveness of this approach. PMID- 25136793 TI - The perception of materials through oral sensation. AB - This paper presents the results of a multimodal study of oral perception conducted with a set of material samples made from metals, polymers and woods, in which both the somatosensory and taste factors were examined. A multidimensional scaling analysis coupled with subjective attribute ratings was performed to assess these factors both qualitatively and quantitatively. The perceptual somatosensory factors of warmth, hardness and roughness dominated over the basic taste factors, and roughness was observed to be a less significant sensation compared to touch-only experiments. The perceptual somatosensory ratings were compared directly with physical property data in order to assess the correlation between the perceived properties and measured physical properties. In each case, a strong correlation was observed, suggesting that physical properties may be useful in industrial design for predicting oral perception. PMID- 25136795 TI - Blood lead levels and associated factors among children in Guiyu of China: a population-based study. AB - OBJECTIVES: Children's health problems caused by the electronic waste (e-waste) lead exposure in China remains. To assess children's blood lead levels (BLLs) in Guiyu of China and investigate risk factors of children's elevated BLLs in Guiyu. MATERIAL AND METHODS: 842 children under 11 years of age from Guiyu and Haojiang were enrolled in this population-based study during 2011-2013. Participants completed a lifestyle and residential environment questionnaire and their physical growth indices were measured, and blood samples taken. Blood samples were tested to assess BLLs. Children's BLLs between the two groups were compared and factors associated with elevated BLLs among Guiyu children were analyzed by group Lasso logistic regression model. RESULTS: Children living in Guiyu had significant higher BLLs (7.06 ug/dL) than the quantity (5.89 ug/dL) of Haojiang children (P<0.05). Subgroup analyses of BLLs exceeding 10 ug/dL showed the proportion (24.80%) of high-level BLLs for Guiyu children was greater than that (12.84%) in Haojiang (P<0.05). Boys had greater BLLs than girls, irrespectively of areas (P<0.05). The number of e-waste piles or recycling workshops around the house (odds ratio, 2.28; 95% confidence interval [CI], 1.37 to 3.87) significantly contributed to the elevated BLLs of children in Guiyu, and girls had less risk (odds ratio, 0.51; 95% CI, 0.31 to 0.83) of e-waste lead exposure than boys. CONCLUSIONS: This analysis reinforces the importance of shifting e waste recycling piles or workshops to non-populated areas as part of a comprehensive response to e-waste lead exposure control in Guiyu. To correct the problem of lead poisoning in children in Guiyu should be a long-term mission. PMID- 25136797 TI - A systematic review of financial debt in adolescents and young adults: prevalence, correlates and associations with crime. AB - Financial debt in young people has increased in recent years. Because debt may have severe consequences, and it may enhance criminal behavior, insight into the prevalence and determinants of debt and its association with crime is important. We conducted a systematic review and meta-analysis of 36 manuscripts to examine the prevalence of financial debt (k = 23), correlates and risk factors of debt (k = 16), and associations between debt and criminal behavior in adolescents and young adults (k = 8). Findings revealed that the prevalence of debt is substantial among young people; on average, 49% reported to have at least some debt, 22% had financial problems. Older participants and ethnic minorities were found to have higher levels of debt than younger and indigenous counterparts. Females had more financial problems and higher student loans. Low self-esteem, a pro-debt attitude (of young people and their parents), lack of perceived control towards financial management, poor social functioning, financial stress and external locus of control were found to have the strongest associations with debt. Studies reported strong associations between debt and crime. Particularly, strong associations were found between serious and persistent crime in young people and later (young adult) debt or financial problems. PMID- 25136798 TI - On the use of leaf spectral indices to assess water status and photosynthetic limitations in Olea europaea L. during water-stress and recovery. AB - Diffusional limitations to photosynthesis, relative water content (RWC), pigment concentrations and their association with reflectance indices were studied in olive (Olea europaea) saplings subjected to water-stress and re-watering. RWC decreased sharply as drought progressed. Following rewatering, RWC gradually increased to pre-stress values. Photosynthesis (A), stomatal conductance (gs), mesophyll conductance (gm), total conductance (gt), photochemical reflectance index (PRI), water index (WI) and relative depth index (RDI) closely followed RWC. In contrast, carotenoid concentration, the carotenoid to chlorophyll ratio, water content reflectance index (WCRI) and structural independent pigment index (SIPI) showed an opposite trend to that of RWC. Photosynthesis scaled linearly with leaf conductance to CO2; however, A measured under non-photorespiratory conditions (A1%O2) was approximately two times greater than A measured at 21% [O2], indicating that photorespiration likely increased in response to drought. A1%O2 also significantly correlated with leaf conductance parameters. These relationships were apparent in saturation type curves, indicating that under non photorespiratory conditions, CO2 conductance was not the major limitations to A. PRI was significant correlated with RWC. PRI was also very sensitive to pigment concentrations and photosynthesis, and significantly tracked all CO2 conductance parameters. WI, RDI and WCRI were all significantly correlated with RWC, and most notably to leaf transpiration. Overall, PRI correlated more closely with carotenoid concentration than SIPI; whereas WI tracked leaf transpiration more effectively than RDI and WCRI. This study clearly demonstrates that PRI and WI can be used for the fast detection of physiological traits of olive trees subjected to water-stress. PMID- 25136800 TI - Effects of infection by Trypanosoma cruzi and Trypanosoma rangeli on the reproductive performance of the vector Rhodnius prolixus. AB - The insect Rhodnius prolixus is responsible for the transmission of Trypanosoma cruzi, which is the etiological agent of Chagas disease in areas of Central and South America. Besides this, it can be infected by other trypanosomes such as Trypanosoma rangeli. The effects of these parasites on vectors are poorly understood and are often controversial so here we focussed on possible negative effects of these parasites on the reproductive performance of R. prolixus, specifically comparing infected and uninfected couples. While T. cruzi infection did not delay pre-oviposition time of infected couples at either temperature tested (25 and 30 degrees C) it did, at 25 degrees C, increase the e-value in the second reproductive cycle, as well as hatching rates. Meanwhile, at 30 degrees C, T. cruzi infection decreased the e-value of insects during the first cycle and also the fertility of older insects. When couples were instead infected with T. rangeli, pre-oviposition time was delayed, while reductions in the e-value and hatching rate were observed in the second and third cycles. We conclude that both T. cruzi and T. rangeli can impair reproductive performance of R. prolixus, although for T. cruzi, this is dependent on rearing temperature and insect age. We discuss these reproductive costs in terms of potential consequences on triatomine behavior and survival. PMID- 25136803 TI - An alteration in ATG16L1 stability in Crohn disease. AB - Individuals who harbor a common coding polymorphism (Thr300Ala) within a structurally unclassified region of ATG16L1 are at increased risk for the development of Crohn disease. Recently, we reported on the generation and characterization of knockin mice carrying the ATG16L1 T300A variant. We demonstrate that multiple cell types from T300A knock-in mice exhibit reduced selective autophagy, and we mechanistically link this phenotype with an increased susceptibility of ATG16L1 T300A to CASP3- and CASP7-mediated cleavage. These findings demonstrate how a single polymorphism can result in cell type- and pathway-specific disruptions of selective autophagy and alterations in the inflammatory milieu that can contribute to disease. PMID- 25136801 TI - Regulation of autophagy and chloroquine sensitivity by oncogenic RAS in vitro is context-dependent. AB - Chloroquine (CQ) is an antimalarial drug and late-stage inhibitor of autophagy currently FDA-approved for use in the treatment of rheumatoid arthritis and other autoimmune diseases. Based primarily on its ability to inhibit autophagy, CQ and its derivative, hydroxychloroquine, are currently being investigated as primary or adjuvant therapy in multiple clinical trials for cancer treatment. Oncogenic RAS has previously been shown to regulate autophagic flux, and cancers with high incidence of RAS mutations, such as pancreatic cancer, have been described in the literature as being particularly susceptible to CQ treatment, leading to the hypothesis that oncogenic RAS makes cancer cells dependent on autophagy. This autophagy "addiction" suggests that the mutation status of RAS in tumors could identify patients who would be more likely to benefit from CQ therapy. Here we show that RAS mutation status itself is unlikely to be beneficial in such a patient selection because oncogenic RAS does not always promote autophagy addiction. Moreover, oncogenic RAS can have opposite effects on both autophagic flux and CQ sensitivity in different cells. Finally, for any given cell type, the positive or negative effect of oncogenic RAS on autophagy does not necessarily predict whether RAS will promote or inhibit CQ-mediated toxicity. Thus, although our results confirm that different tumor cell lines display marked differences in how they respond to autophagy inhibition, these differences can occur irrespective of RAS mutation status and, in different contexts, can either promote or reduce chloroquine sensitivity of tumor cells. PMID- 25136802 TI - A role of autophagy in PTP4A3-driven cancer progression. AB - Autophagy, a "self-eating" cellular process, has dual roles in promoting and suppressing tumor growth, depending on cellular context. PTP4A3/PRL-3, a plasma membrane and endosomal phosphatase, promotes multiple oncogenic processes including cell proliferation, invasion, and cancer metastasis. In this study, we demonstrate that PTP4A3 accumulates in autophagosomes upon inhibition of autophagic degradation. Expression of PTP4A3 enhances PIK3C3-BECN1-dependent autophagosome formation and accelerates LC3-I to LC3-II conversion in an ATG5 dependent manner. PTP4A3 overexpression also enhances the degradation of SQSTM1, a key autophagy substrate. These functions of PTP4A3 are dependent on its catalytic activity and prenylation-dependent membrane association. These results suggest that PTP4A3 functions to promote canonical autophagy flux. Unexpectedly, following autophagy activation, PTP4A3 serves as a novel autophagic substrate, thereby establishing a negative feedback-loop that may be required to fine-tune autophagy activity. Functionally, PTP4A3 utilizes the autophagy pathway to promote cell growth, concomitant with the activation of AKT. Clinically, from the largest ovarian cancer data set (GSE 9899, n = 285) available in GEO, high levels of expression of both PTP4A3 and autophagy genes significantly predict poor prognosis of ovarian cancer patients. These studies reveal a critical role of autophagy in PTP4A3-driven cancer progression, suggesting that autophagy could be a potential Achilles heel to block PTP4A3-mediated tumor progression in stratified patients with high expression of both PTP4A3 and autophagy genes. PMID- 25136806 TI - Insignificant medium-term vitamin D status change after 25-hydroxyvitamin D testing in a large managed care population. AB - OBJECTIVES: To examine the clinical utility of 25-hydroxyvitamin D (25(OH)D) testing in achieving medium-term vitamin D (VD) sufficiency in a managed care population. METHODS: Retrospective study of a continuously-enrolled patient population in a 3-year period between 2011 and 2013. Primary outcome was VD status at ~1 year after 25(OH)D testing. Patient demographics, comorbidities, medications, and 25(OH)D test results were gathered from relevant databases and multivariate logistic regression analysis used to study the risk factors of persistent VD deficiency or insufficiency. RESULTS: Of 22,784 patients, 7533 (females 69.3%) did 14,563 25(OH)D tests, with an estimated cost of $582,520. Of the 7533 patients, 1126 had another 25(OH)D test at 300-400 days after the first one. Based on the two test results, 234 patients (20.8%) maintained sufficient 25(OH)D levels; 132 (11.7%) turned from VD-sufficient into VD-insufficient or deficient; 538 (47.8%) remained VD-insufficient or -deficient, and only 222 (19.7%) improved to be VD-sufficient. Overall, only 8.0% more patients were VD sufficient at ~1 year after 25(OH)D testing. Only younger age and higher BMI were independent risk factors for persistent low 25(OH)D levels and high-dose VD use was not associated with achieving VD sufficiency. CONCLUSIONS: 25(OH)D testing only benefits a small portion of patients thus lacks clinical utility in achieving VD sufficiency in the medium term but incurs a significant cost. A practical strategy to treat VD deficiency or insufficiency is needed; without it, 25(OH)D testing adds little value to most patients' health and should be used with discretion. PMID- 25136805 TI - Transcriptome analysis of the oil-rich tea plant, Camellia oleifera, reveals candidate genes related to lipid metabolism. AB - BACKGROUND: Rapidly driven by the need for developing sustainable sources of nutritionally important fatty acids and the rising concerns about environmental impacts after using fossil oil, oil-plants have received increasing awareness nowadays. As an important oil-rich plant in China, Camellia oleifera has played a vital role in providing nutritional applications, biofuel productions and chemical feedstocks. However, the lack of C. oleifera genome sequences and little genetic information have largely hampered the urgent needs for efficient utilization of the abundant germplasms towards modern breeding efforts of this woody oil-plant. RESULTS: Here, using the 454 GS-FLX sequencing platform, we generated approximately 600,000 RNA-Seq reads from four tissues of C. oleifera. These reads were trimmed and assembled into 104,842 non-redundant putative transcripts with a total length of ~38.9 Mb, representing more than 218-fold of all the C. oleifera sequences currently deposited in the GenBank (as of March 2014). Based on the BLAST similarity searches, nearly 42.6% transcripts could be annotated with known genes, conserved domains, or Gene Ontology (GO) terms. Comparisons with the cultivated tea tree, C. sinensis, identified 3,022 pairs of orthologs, of which 211 exhibited the evidence under positive selection. Pathway analysis detected the majority of genes potentially related to lipid metabolism. Evolutionary analysis of omega-6 fatty acid desaturase (FAD2) genes among 20 oil plants unexpectedly suggests that a parallel evolution may occur between C. oleifera and Olea oleifera. Additionally, more than 2,300 simple sequence repeats (SSRs) and 20,200 single-nucleotide polymorphisms (SNPs) were detected in the C. oleifera transcriptome. CONCLUSIONS: The generated transcriptome represents a considerable increase in the number of sequences deposited in the public databases, providing an unprecedented opportunity to discover all related-genes associated with lipid metabolic pathway in C. oleifera. It will greatly enhance the generation of new varieties of C. oleifera with increased yields and high quality. PMID- 25136807 TI - [Arthrogenic muscle inhibition after trauma - is there an age dependency of the intensity of arthrogenic muscle inhibition?]. AB - Backround: Knee trauma with arthrogenic muscle inhibition (AMI) lead to muscle weakness. The aim of this study was to analyse the intensity of AMI after meniscus and cartilage injuries and to investigate the association between age, BMI and severity of cartilage leasions with AMI. PATIENTS AND METHODS: 48 patients with meniscus or cartilage injury were preoperatively interviewed and examined for isometric maximum force values of the extension muscles of the knee joints. We analysed AMI as comparison of maximum isometric force values between healthy and injured leg by use of Wilcoxon matched pairs test. Moreover a regression analysis was done to assess the association between age, BMI and severity of cartilage lesion with AMI. RESULTS: Trauma of the knee joint with meniscus or cartilage injuries led to a 23.6 % reduction of maximum force values of injured in comparison to healthy leg (460.1 +/- 223.6 N vs. 601.9 +/- 224.6 N, P < 0,000001) in mean. Regression analysis did not show associations between age (beta -2.645, P = 0.345), BMI (beta 2.268, P = 0.792) or severity of cartilage damage (beta -13.527, P = 0.670) with AMI. CONCLUSIONS: Trauma of the knee joint with meniscus or cartilage damage cause an AMI with 23.6 % force reduction. We could not identify an association between age and AMI. PMID- 25136804 TI - Abeta1-42 monomers or oligomers have different effects on autophagy and apoptosis. AB - The role of autophagy and its relationship with apoptosis in Alzheimer disease (AD) pathogenesis is poorly understood. Disruption of autophagy leads to buildup of incompletely digested substrates, amyloid-beta (Abeta) peptide accumulation in vacuoles and cell death. Abeta, in turn, has been found to affect autophagy. Thus, Abeta might be part of a loop in which it is both the substrate of altered autophagy and its cause. Given the relevance of different soluble forms of Abeta1 42 in AD, we have investigated whether monomers and oligomers of the peptide have a differential role in causing altered autophagy and cell death. Using differentiated SK-N-BE neuroblastoma cells, we found that monomers hamper the formation of the autophagic BCL2-BECN1/Beclin 1 complex and activate the MAPK8/JNK1-MAPK9/JNK2 pathway phosphorylating BCL2. Monomers also inhibit apoptosis and allow autophagy with intracellular accumulation of autophagosomes and elevation of levels of BECN1 and LC3-II, resulting in an inhibition of substrate degradation due to an inhibitory action on lysosomal activity. Oligomers, in turn, favor the formation of the BCL2-BECN1 complex favoring apoptosis. In addition, they cause a less profound increase in BECN1 and LC3-II levels than monomers without affecting the autophagic flux. Thus, data presented in this work show a link for autophagy and apoptosis with monomers and oligomers, respectively. These studies are likely to help the design of novel disease modifying therapies. PMID- 25136808 TI - The response of human thermal sensation and its prediction to temperature step change (cool-neutral-cool). AB - This paper reports on studies of the effect of temperature step-change (between a cool and a neutral environment) on human thermal sensation and skin temperature. Experiments with three temperature conditions were carried out in a climate chamber during the period in winter. Twelve subjects participated in the experiments simulating moving inside and outside of rooms or cabins with air conditioning. Skin temperatures and thermal sensation were recorded. Results showed overshoot and asymmetry of TSV due to the step-change. Skin temperature changed immediately when subjects entered a new environment. When moving into a neutral environment from cool, dynamic thermal sensation was in the thermal comfort zone and overshoot was not obvious. Air-conditioning in a transitional area should be considered to limit temperature difference to not more than 5 degrees C to decrease the unacceptability of temperature step-change. The linear relationship between thermal sensation and skin temperature or gradient of skin temperature does not apply in a step-change environment. There is a significant linear correlation between TSV and Qloss in the transient environment. Heat loss from the human skin surface can be used to predict dynamic thermal sensation instead of the heat transfer of the whole human body. PMID- 25136809 TI - Stress hyperglycaemia in hospitalised patients and their 3-year risk of diabetes: a Scottish retrospective cohort study. AB - BACKGROUND: Hyperglycaemia during hospital admission is common in patients who are not known to have diabetes and is associated with adverse outcomes. The risk of subsequently developing type 2 diabetes, however, is not known. We linked a national database of hospital admissions with a national register of diabetes to describe the association between admission glucose and the risk of subsequently developing type 2 diabetes. METHODS AND FINDINGS: In a retrospective cohort study, patients aged 30 years or older with an emergency admission to hospital between 2004 and 2008 were included. Prevalent and incident diabetes were identified through the Scottish Care Information (SCI)-Diabetes Collaboration national registry. Patients diagnosed prior to or up to 30 days after hospitalisation were defined as prevalent diabetes and were excluded. The predicted risk of developing incident type 2 diabetes during the 3 years following hospital discharge by admission glucose, age, and sex was obtained from logistic regression models. We performed separate analyses for patients aged 40 and older, and patients aged 30 to 39 years. Glucose was measured in 86,634 (71.0%) patients aged 40 and older on admission to hospital. The 3-year risk of developing type 2 diabetes was 2.3% (1,952/86,512) overall, was <1% for a glucose <= 5 mmol/l, and increased to approximately 15% at 15 mmol/l. The risks at 7 mmol/l and 11.1 mmol/l were 2.6% (95% CI 2.5-2.7) and 9.9% (95% CI 9.2-10.6), respectively, with one in four (21,828/86,512) and one in 40 (1,798/86,512) patients having glucose levels above each of these cut-points. For patients aged 30-39, the risks at 7 mmol/l and 11.1 mmol/l were 1.0% (95% CI 0.8-1.3) and 7.8% (95% CI 5.7-10.7), respectively, with one in eight (1,588/11,875) and one in 100 (120/11,875) having glucose levels above each of these cut-points. The risk of diabetes was also associated with age, sex, and socio-economic deprivation, but not with specialty (medical versus surgical), raised white cell count, or co morbidity. Similar results were obtained for pre-specified sub-groups admitted with myocardial infarction, chronic obstructive pulmonary disease, and stroke. There were 25,193 deaths (85.8 per 1,000 person-years) over 297,122 person-years, of which 2,406 (8.1 per 1,000 person-years) were attributed to vascular disease. Patients with glucose levels of 11.1 to 15 mmol/l and >15 mmol/l had higher mortality than patients with a glucose of <6.1 mmol/l (hazard ratio 1.54; 95% CI 1.42-1.68 and 2.50; 95% CI 2.14-2.95, respectively) in models adjusting for age and sex. Limitations of our study include that we did not have data on ethnicity or body mass index, which may have improved prediction and the results have not been validated in non-white populations or populations outside of Scotland. CONCLUSION: Plasma glucose measured during an emergency hospital admission predicts subsequent risk of developing type 2 diabetes. Mortality was also 1.5 fold higher in patients with elevated glucose levels. Our findings can be used to inform patients of their long-term risk of type 2 diabetes, and to target lifestyle advice to those patients at highest risk. Please see later in the article for the Editors' Summary. PMID- 25136810 TI - A quantitative prioritisation of human and domestic animal pathogens in Europe. AB - Disease or pathogen risk prioritisations aid understanding of infectious agent impact within surveillance or mitigation and biosecurity work, but take significant development. Previous work has shown the H-(Hirsch-)index as an alternative proxy. We present a weighted risk analysis describing infectious pathogen impact for human health (human pathogens) and well-being (domestic animal pathogens) using an objective, evidence-based, repeatable approach; the H index. This study established the highest H-index European pathogens. Commonalities amongst pathogens not included in previous surveillance or risk analyses were examined. Differences between host types (humans/animals/zoonotic) in pathogen H-indices were explored as a One Health impact indicator. Finally, the acceptability of the H-index proxy for animal pathogen impact was examined by comparison with other measures. 57 pathogens appeared solely in the top 100 highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67 and 57 for animals. There were statistically significant differences between H indices for host types (humans, animal, zoonotic), and there was limited evidence that H-indices are a reasonable proxy for animal pathogen impact. This work addresses measures outlined by the European Commission to strengthen climate change resilience and biosecurity for infectious diseases. The results include a quantitative evaluation of infectious pathogen impact, and suggest greater impacts of human-only compared to zoonotic pathogens or scientific under representation of zoonoses. The outputs separate high and low impact pathogens, and should be combined with other risk assessment methods relying on expert opinion or qualitative data for priority setting, or could be used to prioritise diseases for which formal risk assessments are not possible because of data gaps. PMID- 25136811 TI - Combination effect of epigenetic regulation and ionizing radiation in colorectal cancer cells. AB - Exposure of cells to ionizing radiation (IR) induces, not only, activation of multiple signaling pathways that play critical roles in cell fate determination, but also alteration of molecular pathways involved in cell death or survival. Recently, DNA methylation has been established as a critical epigenetic process involved in the regulation of gene expression in cancer cells, suggesting that DNA methylation inhibition may be an effective cancer treatment strategy. Because alterations of gene expression by DNA methylation have been considered to influence radioresponsiveness, we investigated the effect of a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), on radiosensitivity. In addition, we investigated the underlying cellular mechanisms of combination treatments of ionizing irradiation (IR) and 5-aza-dC in human colon cancer cells. Colon cancer cell lines were initially tested for radiation sensitivity by IR in vitro and were treated with two different doses of 5-aza-dC. Survival of these cell lines was measured using MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide) and clonogenic assays. The effects of 5-aza-dC along with irradiation on cell growth, cell cycle distribution, apoptosis, and apoptosis-related gene expression were examined. Combination irradiation treatment with 5-aza-dC significantly decreased growth activity compared with irradiation treatment alone or with 5-aza-dC treatment alone. The percentage of HCT116 cells in the sub-G1 phase and their apoptotic rate was increased when cells were treated with irradiation in combination with 5-aza-dC compared with either treatment alone. These observations were strongly supported by increased caspase activity, increased comet tails using comet assays, and increased protein levels of apoptosis-associated molecules (caspase 3/9, cleaved PARP). Our data demonstrated that 5-aza-dC enhanced radiosensitivity in colon cancer cells, and the combination effects of 5-aza-dC with radiation showed greater cellular effects than that of single treatment, suggesting that the combination of 5-aza dC and radiation has the potential to become a clinical strategy for the treatment of cancer. PMID- 25136812 TI - The Snail transcription factor regulates the numbers of neural precursor cells and newborn neurons throughout mammalian life. AB - The Snail transcription factor regulates diverse aspects of stem cell biology in organisms ranging from Drosophila to mammals. Here we have asked whether it regulates the biology of neural precursor cells (NPCs) in the forebrain of postnatal and adult mice, taking advantage of a mouse containing a floxed Snail allele (Snailfl/fl mice). We show that when Snail is inducibly ablated in the embryonic cortex, this has long-term consequences for cortical organization. In particular, when Snailfl/fl mice are crossed to Nestin-cre mice that express Cre recombinase in embryonic neural precursors, this causes inducible ablation of Snail expression throughout the postnatal cortex. This loss of Snail causes a decrease in proliferation of neonatal cortical neural precursors and mislocalization and misspecification of cortical neurons. Moreover, these precursor phenotypes persist into adulthood. Adult neural precursor cell proliferation is decreased in the forebrain subventricular zone and in the hippocampal dentate gyrus, and this is coincident with a decrease in the number of adult-born olfactory and hippocampal neurons. Thus, Snail is a key regulator of the numbers of neural precursors and newborn neurons throughout life. PMID- 25136813 TI - Gene-specific function prediction for non-synonymous mutations in monogenic diabetes genes. AB - The rapid progress of genomic technologies has been providing new opportunities to address the need of maturity-onset diabetes of the young (MODY) molecular diagnosis. However, whether a new mutation causes MODY can be questionable. A number of in silico methods have been developed to predict functional effects of rare human mutations. The purpose of this study is to compare the performance of different bioinformatics methods in the functional prediction of nonsynonymous mutations in each MODY gene, and provides reference matrices to assist the molecular diagnosis of MODY. Our study showed that the prediction scores by different methods of the diabetes mutations were highly correlated, but were more complimentary than replacement to each other. The available in silico methods for the prediction of diabetes mutations had varied performances across different genes. Applying gene-specific thresholds defined by this study may be able to increase the performance of in silico prediction of disease-causing mutations. PMID- 25136816 TI - Plasma anti-mullerian hormone: an endocrine marker for in vitro embryo production from Bos taurus and Bos indicus donors. AB - The aim of this study was to evaluate the association between plasma anti mullerian hormone (AMH) concentration and in vitro embryo production (IVP) from Bos taurus (Holstein) and Bos indicus (Nelore) donors. A total of 59 Holstein (15 prepubertal heifers aged 8-10 mo, 15 cyclic heifers aged 12-14 mo, 14 lactating cows, and 15 nonlactating cows) and 34 Nelore (12 prepubertal heifers aged 10-11 mo, 10 prepubertal heifers aged 21-23 mo, and 12 cyclic heifers aged 24-26 mo) females were enrolled. All females underwent an ovum pick-up (OPU), without previous synchronization of the follicular wave, and IVP procedure. Immediately before the OPU procedure, blood samples were collected for subsequent AMH determination. A positive correlation was observed between the plasma AMH and number of in vitro embryos produced from Holstein (r = 0.36, P < 0.001) and Nelore (r = 0.50, P = 0.003) donors. For additional analyses, donors within each genotype were classified into 1 of 2 AMH categories (low or high) according to the average AMH concentration for each genotype. The results revealed that females classified as having high AMH presented a greater number of visible aspirated follicles (Holstein: 20.9 +/- 1.5 vs 13.6 +/- 0.9, P < 0.0001; Nelore: 54.3 +/- 6.1 vs 18.6 +/- 2.1, P < 0.0001) and a greater number of recovered cumulus-oocyte complexes (Holstein: 17.3 +/- 1.5 vs 9.0 +/- 0.9, P < 0.0001; Nelore: 45.3 +/- 6.4 vs 13.4 +/- 1.7, P < 0.0001). However, there was no difference in the blastocyst production rate (Holstein: 20.6% +/- 4.0% vs 19.8% +/- 4.2%, P = 0.60; Nelore: 33.7% +/- 6.5% vs 27.4% +/- 5.5%, P = 0.41, high and low AMH, respectively). Moreover, donors classified as having high AMH yielded a greater number of embryos produced per OPU (Holstein: 3.0 +/- 0.7; Nelore: 7.0 +/ 1.7) compared with those classified as having low AMH (Holstein: 1.2 +/- 0.3, P = 0.04; Nelore: 2.2 +/- 0.5, P = 0.007). In conclusion, although the plasma AMH concentration did not alter the ability of the cumulus-oocyte complex to reach the blastocyst stage, the AMH concentration in plasma can be an accurate endocrine marker for the in vitro embryo yield from either B. taurus (Holstein) or B. indicus (Nelore) donors. Therefore, AMH is a promising tool to enhance the overall efficiency of OPU-IVP programs in the field as a selective criterion for high embryo producing donors. PMID- 25136814 TI - Immobilization of captive tigers (Panthera tigris) with a combination of tiletamine, zolazepam, and detomidine. AB - The aims of this study were to evaluate the effects of the administration of a combination of tiletamine-zolazepam and detomidine (TZD) in 9 tigers (Panthera tigris). Nine captive tigers were immobilized with tiletamine-zolazepam and detomidine administered intramuscularly. At the end of the procedure immobilization was partially reversed with atipamezole. Lateral recumbency was achieved in 15.6 +/- 5.9 min. The median induction score [scored 1 (excellent) to 4 (poor)] was 1. The immobilization score [scored 1 (poor) to 6 (too deep)] was 5 (4-5) at all study times. After atipamezole administration, all tigers experienced severe ataxia and incoordination. Median recovery score [scored 1 (excellent) to 4 (poor)] was 2.5 (range 2-3). No neurologic and/or important adverse reactions were noticed within 5 days after recovery. The combination tiletamine-zolazepam with detomidine proved to be effective in immobilizing captive healthy tigers but it maybe associated with hypertension and ataxia during recovery. Zoo Biol. 34:40-45, 2015. (c) 2014 Wiley Periodicals Inc. PMID- 25136817 TI - Effervescence-assisted dispersive liquid-liquid microextraction using a solid effervescent agent as a novel dispersion technique for the analysis of fungicides in apple juice. AB - A novel effervescence-assisted dispersive liquid-liquid microextraction method has been developed for the determination of four fungicides in apple juice samples. In this method, a solid effervescent agent is added into samples to assist the dispersion of extraction solvent. The effervescent agent is environmentally friendly and only produces an increase in the ionic strength and a negligible variation in the pH value of the aqueous sample, which does not interfere with the extraction of the analytes. The parameters affecting the extraction efficiency were investigated including the composition of effervescent agent, effervescent agent amount, formulation of effervescent agent, adding mode of effervescent agent, type and volume of extraction solvent, and pH. Under optimized conditions, the method showed a good linearity within the range of 0.05 2 mg/L for pyrimethanil, fludioxonil, and cyprodinil, and 0.1-4 mg/L for kresoxim methyl, with the correlation coefficients >0.998. The limits of detection for the method ranged between 0.005 and 0.01 mg/L. The recoveries of the target fungicides in apple juice samples were in the range of 72.4-110.8% with the relative standard deviations ranging from 1.2 to 6.8%. PMID- 25136818 TI - Synthesis of aromatic (13)C/(2)H-alpha-ketoacid precursors to be used in selective phenylalanine and tyrosine protein labelling. AB - Recent progress in protein NMR spectroscopy revealed aromatic residues to be valuable information sources for performing structure and motion analysis of high molecular weight proteins. However, the applied NMR experiments require tailored isotope labelling patterns in order to regulate spin-relaxation pathways and optimize magnetization transfer. We introduced a methodology to use alpha ketoacids as metabolic amino acid precursors in cell-based overexpression of phenylalanine and/or tyrosine labelled proteins in a recent publication, which we have now developed further by providing synthetic routes to access the corresponding side-chain labelled precursors. The target compounds allow for selective introduction of (13)C-(1)H spin systems in a highly deuterated chemical environment and feature alternating (12)C-(13)C-(12)C ring-patterns. The resulting isotope distribution is especially suited to render straightforward (13)C spin relaxation experiments possible, which provide insight into the dynamic properties of the corresponding labelled proteins. PMID- 25136819 TI - Demonstration of ultrarapid interfacial formation of 1D fullerene nanorods with photovoltaic properties. AB - We demonstrate ultrarapid interfacial formation of one-dimensional (1D) single crystalline fullerene C60 nanorods at room temperature in 5 s. The nanorods of ~ 11 MUm in length and ~ 215 nm in diameter are developed in a hexagonal close-pack crystal structure, contrary to the cubic crystal structure of pristine C60. Vibrational and electronic spectroscopy provide strong evidence that the nanorods are a van der Waals solid, as evidenced from the preservation of the electronic structure of the C60 molecules within the rods. Steady state optical spectroscopy reveals a dominance of charge transfer excitonic transitions in the nanorods. A significant enhancement of photogenerated charge carriers is observed in the nanorods in comparison to pristine C60, revealing the effect of shape on the photovoltaic properties. Due to their ultrarapid, large-scale, room-temperature synthesis with single-crystalline structure and excellent optoelectronic properties, the nanorods are expected to be promising for photosensitive devices applications. PMID- 25136820 TI - Links of justice and rejection sensitivity with aggression in childhood and adolescence. AB - Individual differences in justice sensitivity and rejection sensitivity have been linked to differences in aggressive behavior in adults. However, there is little research studying this association in children and adolescents and considering the two constructs in combination. We assessed justice sensitivity from the victim, observer, and perpetrator perspective as well as anxious and angry rejection sensitivity and linked both constructs to different forms (physical, relational), and functions (proactive, reactive) of self-reported aggression and to teacher- and parent-rated aggression in N = 1,489 9- to 19-year olds in Germany. Victim sensitivity and both angry and anxious rejection sensitivity showed positive correlations with all forms and functions of aggression. Angry rejection sensitivity also correlated positively with teacher-rated aggression. Perpetrator sensitivity was negatively correlated with all aggression measures, and observer sensitivity also correlated negatively with all aggression measures except for a positive correlation with reactive aggression. Path models considering the sensitivity facets in combination and controlling for age and gender showed that higher victim justice sensitivity predicted higher aggression on all measures. Higher perpetrator sensitivity predicted lower physical, relational, proactive, and reactive aggression. Higher observer sensitivity predicted lower teacher-rated aggression. Angry rejection sensitivity predicted higher proactive and reactive aggression, whereas anxious rejection sensitivity did not make an additional contribution to the prediction of aggression. The findings are discussed in terms of social information processing models of aggression in childhood and adolescence. PMID- 25136821 TI - Instability of trinucleotidic repeats during chromatin remodeling in spermatids. AB - Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases. PMID- 25136823 TI - Uniform versus asymmetric shading mediates crown recession in conifers. AB - In this study we explore the impact of asymmetrical vs. uniform crown shading on the mortality and growth of upper and lower branches within tree crowns, for two conifer species: shade intolerant lodgepole pine (Pinus contorta) and shade tolerant white spruce (Picea glauca). We also explore xylem hydraulics, foliar nutrition, and carbohydrate status as drivers for growth and expansion of the lower and upper branches in various types of shading. This study was conducted over a two-year period across 10 regenerating forest sites dominated by lodgepole pine and white spruce, in the lower foothills of Alberta, Canada. Trees were assigned to one of four shading treatments: (1), complete uniform shading of the entire tree, (2) light asymmetric shading where the lower 1/4-1/3 of the tree crown was shaded, (3) heavy asymmetric shading as in (2) except with greater light reduction and (4) control in which no artificial shading occurred and most of the entire crown was exposed to full light. Asymmetrical shading of only the lower crown had a larger negative impact on the bud expansion and growth than did uniform shading, and the effect was stronger in pine relative to spruce. In addition, lower branches in pine also had lower carbon reserves, and reduced xylem-area specific conductivity compared to spruce. For both species, but particularly the pine, the needles of lower branches tended to store less C than upper branches in the asymmetric shade, which could suggest a movement of reserves away from the lower branches. The implications of these findings correspond with the inherent shade tolerance and self-pruning behavior of these conifers and supports a carbon based mechanism for branch mortality--mediated by an asymmetry in light exposure of the crown. PMID- 25136824 TI - Differential axonal conduction patterns of mechano-sensitive and mechano insensitive nociceptors--a combined experimental and modelling study. AB - Cutaneous pain sensations are mediated largely by C-nociceptors consisting of both mechano-sensitive (CM) and mechano-insensitive (CMi) fibres that can be distinguished from one another according to their characteristic axonal properties. In healthy skin and relative to CMi fibres, CM fibres show a higher initial conduction velocity, less activity-dependent conduction velocity slowing, and less prominent post-spike supernormality. However, after sensitization with nerve growth factor, the electrical signature of CMi fibres changes towards a profile similar to that of CM fibres. Here we take a combined experimental and modelling approach to examine the molecular basis of such alterations to the excitation thresholds. Changes in electrical activation thresholds and activity dependent slowing were examined in vivo using single-fibre recordings of CM and CMi fibres in domestic pigs following NGF application. Using computational modelling, we investigated which axonal mechanisms contribute most to the electrophysiological differences between the fibre classes. Simulations of axonal conduction suggest that the differences between CMi and CM fibres are strongly influenced by the densities of the delayed rectifier potassium channel (Kdr), the voltage-gated sodium channels NaV1.7 and NaV1.8, and the Na+/K+-ATPase. Specifically, the CM fibre profile required less Kdr and NaV1.8 in combination with more NaV1.7 and Na+/K+-ATPase. The difference between CM and CMi fibres is thus likely to reflect a relative rather than an absolute difference in protein expression. In support of this, it was possible to replicate the experimental reduction of the ADS pattern of CMi nociceptors towards a CM-like pattern following intradermal injection of nerve growth factor by decreasing the contribution of Kdr (by 50%), increasing the Na+/K+-ATPase (by 10%), and reducing the branch length from 2 cm to 1 cm. The findings highlight key molecules that potentially contribute to the NGF-induced switch in nociceptors phenotype, in particular NaV1.7 which has already been identified clinically as a principal contributor to chronic pain states such as inherited erythromelalgia. PMID- 25136825 TI - Deep brain stimulation of the antero-medial globus pallidus interna for Tourette syndrome. AB - BACKGROUND: We have previously reported the results of Deep Brain Stimulation (DBS) of the antero-medial globus pallidus interna (GPi) for severe Tourette Syndrome (TS) in 11 patients. We extend this case series to 17 patients and a longer follow-up to a maximum of 46 months. METHODS: 17 patients (14 male; mean age 29.1 years, range 17-51 years) with severe and medically intractable TS were implanted with Medtronic quadripolar electrodes bilaterally in the antero-medial GPi. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS). Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, Gilles de la Tourette Quality of Life Scale and Global Assessment of Functioning. Follow up was at one month, three months and finally at a mean 24.1 months (range 8-46 months) following surgery. RESULTS: Overall, there was a 48.3% reduction in motor tics and a 41.3% reduction in phonic tics at one month, and this improvement was maintained at final follow-up. 12 out of 17 (70.6%) patients had a>50% reduction in YGTSS score at final follow up. Only 8 patients required ongoing pharmacotherapy for tics post-surgery. Patients improved significantly on all secondary measures. Adverse consequences included lead breakage in 4 patients, infection (1), transient anxiety (2), dizziness (1), poor balance (1) and worsening of stuttering (1). CONCLUSIONS: This case series provides further support that antero-medial GPi DBS is an effective and well tolerated treatment for a subgroup of severe TS, with benefits sustained up to 4 years. PMID- 25136828 TI - Environmental factors associated with success rates of Australian stock herding dogs. AB - This study investigated the current management practices associated with stock herding dogs on Australian farms. A parallel goal was to determine whether these practices and the characteristics of the dog handlers were associated with success rates. Success rate refers to the proportion of dogs acquired by the farmer that were retained as working dogs. Data on a total of 4,027 dogs were obtained through The Farm Dog Survey which gathered information from 812 herding dog owners around Australia. Using logistic regression, significant associations were identified between success rate and seven variables: dog breed, housing method, trial participation, age of the dog at acquisition, electric collar use, hypothetical maximum treatment expenditure and the conscientiousness score of the owner's personality. These findings serve as a guide to direct further research into ways of optimising herding dog performance and welfare. They emphasise the importance of not only examining the genetic predispositions of the working dog but also the impact the handler can have on a dog's success in the workplace. PMID- 25136826 TI - The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells. AB - The flavones apigenin (4',5,7,-trihydroxyflavone) and luteolin (3',4',5,7, tetrahydroxyflavone) are plant secondary metabolites with antioxidant, antiinflammatory, and anticancer activities. We evaluated their impact on cell signaling pathways related to insulin-resistance and type 2 diabetes. Apigenin and luteolin were identified in our U-2 OS (human osteosarcoma) cell screening assay for micronutrients triggering rapid intracellular translocation of the forkhead box transcription factor O1 (FOXO1), an important mediator of insulin signal transduction. Insulin reversed the translocation of FOXO1 as shown by live cell imaging. The impact on the expression of target genes was evaluated in HepG2 (human hepatoma) cells. The mRNA-expression of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pc), the lipogenic enzymes fatty-acid synthase (FASN) and acetyl-CoA-carboxylase (ACC) were down-regulated by both flavones with smaller effective dosages of apigenin than for luteolin. PKB/AKT-, PRAS40-, p70S6K-, and S6-phosphorylation was reduced by apigenin and luteolin but not that of the insulin-like growth factor receptor IGF-1R by apigenin indicating a direct inhibition of the PKB/AKT-signaling pathway distal to the IGF-1 receptor. N-acetyl-L-cysteine did not prevent FOXO1 nuclear translocation induced by apigenin and luteolin, suggesting that these flavones do not act via oxidative stress. The roles of FOXO1, FOXO3a, AKT, sirtuin1 (SIRT1), and nuclear factor (erythroid-derived2)-like2 (NRF2), investigated by siRNA knockdown, showed differential patterns of signal pathways involved and a role of NRF2 in the inhibition of gluconeogenic enzyme expression. We conclude that these flavones show an antidiabetic potential due to reduction of gluconeogenic and lipogenic capacity despite inhibition of the PKB/AKT pathway which justifies detailed investigation in vivo. PMID- 25136829 TI - No correlation between TIMP2 -418 G>C polymorphism and increased risk of cancer: evidence from a meta-analysis. AB - AIM: Tissue inhibitor of metalloproteinase (TIMP2) is involved in the regulation of matrix metalloproteinase 2 (MMP2) and shown to implicate in cancer development and progression. The results from the published studies based on the association between TIMP2 -418 G>C polymorphism and cancer risk are inconsistent. In this meta-analysis, we aimed to evaluate the potential association between TIMP2 -418 G>C polymorphism and cancer risk. METHODOLOGY: We searched PubMed (Medline) and EMBASE web databases to cover all studies based on relationship of TIMP2 -418 G>C polymorphism and risk of cancer until October 2013. The meta-analysis was performed for selected case-control studies and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all genetic models. RESULTS: A total of 2225 cancer cases and 2532 controls were included from ten eligible case control studies. Results from overall pooled analysis suggested no evidence of significant risk between TIMP2 -418 G>C polymorphism and cancer risk in any of the genetic models, such as, allele (C vs. G: OR = 1.293, 95% CI = 0.882 to 1.894, p = 0.188), homozygous (CC vs. GG: OR = 0.940, 95% CI = 0.434 to 2.039, p = 0.876), heterozygous (GC vs. GG: OR = 1.397, 95% CI = 0.888 to 2.198, p = 0.148), dominant (CC+GC vs. GG: OR = 1.387, 95% CI = 0.880 to 2.187, p = 0.159) and recessive (CC vs. GG+GC: OR = 0.901, 95% CI = 0.442 to 1.838, p = 0.774) models. No evidence of publication bias was detected during the analysis. CONCLUSIONS: The present meta-analysis suggests that the TIMP2 -418 G>C polymorphism may not be involved in predisposing risk factor for cancer in overall population. However, future larger studies with group of populations are needed to analyze the possible correlation. PMID- 25136830 TI - Characterization of the regulatory mechanisms of activating transcription factor 3 by hypertrophic stimuli in rat cardiomyocytes. AB - AIMS: Activating transcription factor 3 (ATF3) is a stress-activated immediate early gene suggested to have both detrimental and cardioprotective role in the heart. Here we studied the mechanisms of ATF3 activation by hypertrophic stimuli and ATF3 downstream targets in rat cardiomyocytes. METHODS AND RESULTS: When neonatal rat cardiomyocytes were exposed to endothelin-1 (ET-1, 100 nM) and mechanical stretching in vitro, maximal increase in ATF3 expression occurred at 1 hour. Inhibition of extracellular signal-regulated kinase (ERK) by PD98059 decreased ET-1- and stretch-induced increase of ATF3 protein but not ATF3 mRNA levels, whereas protein kinase A (PKA) inhibitor H89 attenuated both ATF3 mRNA transcription and protein expression in response to ET-1 and stretch. To characterize further the regulatory mechanisms upstream of ATF3, p38 mitogen activated protein kinase (MAPK) signaling was investigated using a gain-of function approach. Adenoviral overexpression of p38alpha, but not p38beta, increased ATF3 mRNA and protein levels as well as DNA binding activity. To investigate the role of ATF3 in hypertrophic process, we overexpressed ATF3 by adenovirus-mediated gene transfer. In vitro, ATF3 gene delivery attenuated the mRNA transcription of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1), and enhanced nuclear factor-kappaB (NF-kappaB) and Nkx-2.5 DNA binding activities. Reduced PAI-1 expression was also detected in vivo in adult rat heart by direct intramyocardial adenovirus-mediated ATF3 gene delivery. CONCLUSIONS: These data demonstrate that ATF3 activation by ET-1 and mechanical stretch is partly mediated through ERK and cAMP-PKA pathways, whereas p38 MAPK pathway is involved in ATF3 activation exclusively through p38alpha isoform. ATF3 activation caused induction of modulators of the inflammatory response NF-kappaB and Nkx 2.5, as well as attenuation of pro-fibrotic and pro-inflammatory proteins IL-6 and PAI-1, suggesting cardioprotective role for ATF3 in the heart. PMID- 25136831 TI - A quantitative comparison of single-cell whole genome amplification methods. AB - Single-cell sequencing is emerging as an important tool for studies of genomic heterogeneity. Whole genome amplification (WGA) is a key step in single-cell sequencing workflows and a multitude of methods have been introduced. Here, we compare three state-of-the-art methods on both bulk and single-cell samples of E. coli DNA: Multiple Displacement Amplification (MDA), Multiple Annealing and Looping Based Amplification Cycles (MALBAC), and the PicoPLEX single-cell WGA kit (NEB-WGA). We considered the effects of reaction gain on coverage uniformity, error rates and the level of background contamination. We compared the suitability of the different WGA methods for the detection of copy-number variations, for the detection of single-nucleotide polymorphisms and for de-novo genome assembly. No single method performed best across all criteria and significant differences in characteristics were observed; the choice of which amplifier to use will depend strongly on the details of the type of question being asked in any given experiment. PMID- 25136832 TI - The transient receptor potential vanilloid 2 cation channel is abundant in macrophages accumulating at the peri-infarct zone and may enhance their migration capacity towards injured cardiomyocytes following myocardial infarction. AB - PURPOSE: A novel family of transient receptor potential (TRP) channels, that may hold a role in calcium homeostasis, has recently been described. By employing a GeneChip array analysis we have demonstrated a clear and specific upregulation of the TRP vanilloid 2 (TRPV2) mRNA in the left ventricles (LV) 3-5 days post-acute myocardial infarction (MI) compared to sham-operated controls, both in rats and in mice. We sought to characterize the cardiac cellular subpopulations in which TRPV2 is overexpressed upon acute MI. METHODS: Lewis rats underwent an acute MI by ligation of the left anterior descending artery or chest opening only (sham). The animals were terminated at various time points and an immunohistochemical (IHC) and immunofluorescent (IFC) staining of the LV sections as well as a flow cytometry analysis of LV-derived cells were carried out, using anti-TRPV2 and anti-monocyte/macrophage antibodies. Rat alveolar macrophage cells, NR8383, transiently transfected with TRPV2 siRNA were allowed to migrate towards hypoxic conditioned media of the rat cardiac myoblast line H9C2 using a trans-well migration assay. The macrophage cells migrating to the bottom side of the inserts were counted. RESULTS: The IHC and IFC staining as well as the flow cytometry data demonstrated a substantial expression of TRPV2 in infiltrating macrophages in the peri-infarct region 3-5 days post-acute MI. The in vitro migration assay data demonstrated that following inhibition of the TRPV2 channel, the number of migrating macrophages towards conditioned medium of hypoxic cardiomyocytes was significantly reduced. CONCLUSIONS: TRPV2 is highly expressed on the peri-infarct infiltrating macrophages and may play an important role in post-MI phagocytosis. Better characterization of this channel may pave the way for identifying a new target for modulating the dramatic post-MI immune reactions. PMID- 25136833 TI - HLXB9 gene expression, and nuclear location during in vitro neuronal differentiation in the SK-N-BE neuroblastoma cell line. AB - Different parts of the genome occupy specific compartments of the cell nucleus based on the gene content and the transcriptional activity. An example of this is the altered nuclear positioning of the HLXB9 gene in leukaemia cells observed in association with its over-expression. This phenomenon was attributed to the presence of a chromosomal translocation with breakpoint proximal to the HLXB9 gene. Before becoming an interesting gene in cancer biology, HLXB9 was studied as a developmental gene. This homeobox gene is also known as MNX1 (motor neuron and pancreas homeobox 1) and it is relevant for both motor neuronal and pancreatic beta cells development. A spectrum of mutations in this gene are causative of sacral agenesis and more broadly, of what is known as the Currarino Syndrome, a constitutional autosomal dominant disorder. Experimental work on animal models has shown that HLXB9 has an essential role in motor neuronal differentiation. Here we present data to show that, upon treatment with retinoic acid, the HLXB9 gene becomes over-expressed during the early stages of neuronal differentiation and that this corresponds to a reposition of the gene in the nucleus. More precisely, we used the SK-N-BE human neuroblastoma cell line as an in vitro model and we demonstrated a transient transcription of HLXB9 at the 4th and 5th days of differentiation that corresponded to the presence, predominantly in the cell nuclei, of the encoded protein HB9. The nuclear positioning of the HLXB9 gene was monitored at different stages: a peripheral location was noted in the proliferating cells whereas a more internal position was noted during differentiation, that is while HLXB9 was transcriptionally active. Our findings suggest that HLXB9 can be considered a marker of early neuronal differentiation, possibly involving chromatin remodeling pathways. PMID- 25136834 TI - Complement factor H, vitronectin, and opticin are tyrosine-sulfated proteins of the retinal pigment epithelium. AB - Lack of tyrosine sulfation of ocular proteins results in disorganized photoreceptor structure and drastically reduced visual function, demonstrating the importance of this post-translational modification to vision. To understand the role that tyrosine sulfation plays in the function of ocular proteins, we identified some tyrosine-sulfated proteins in the retinal pigment epithelium using two independent methods, immuno-affinity column purification with an anti sulfotyrosine specific antibody and computer-based sequence analysis of retinal pigment epithelium secretome by means of the prediction program Sulfinator. Radioactive labeling followed by thin layer electrophoresis revealed that three proteins, vitronectin, opticin, and complement factor H (CFH), were post translationally modified by tyrosine sulfation. The identification of vitronectin and CFH as tyrosine-sulfated proteins is significant, since both are deposited in drusen in the eyes of patients with age-related macular degeneration (AMD). Furthermore, mutations in CFH have been determined to be a major risk factor in the development of AMD. Future studies that seek to understand the role of CFH in the development of AMD should take into account the role that tyrosine sulfation plays in the interaction of this protein with its partners, and examine whether modulating sulfation provides a potential therapeutic target. PMID- 25136835 TI - NLRP3 gene silencing ameliorates diabetic cardiomyopathy in a type 2 diabetes rat model. AB - BACKGROUND: Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is associated with metabolic disorder and cell death, which are important triggers in diabetic cardiomyopathy (DCM). We aimed to explore whether NLRP3 inflammasome activation contributes to DCM and the mechanism involved. METHODS: Type 2 diabetic rat model was induced by high fat diet and low dose streptozotocin. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. Gene silencing therapy was used to investigate the role of NLRP3 in the pathogenesis of DCM. High glucose treated H9c2 cardiomyocytes were used to determine the mechanism by which NLRP3 modulated the DCM. The cell death in vitro was detected by TUNEL and EthD-III staining. TXNIP-siRNA and pharmacological inhibitors of ROS and NF-kB were used to explore the mechanism of NLRP3 inflammasome activation. RESULTS: Diabetic rats showed severe metabolic disorder, cardiac inflammation, cell death, disorganized ultrastructure, fibrosis and excessive activation of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), pro-caspase-1, activated caspase-1 and mature interleukin-1beta (IL-1beta). Evidence for pyroptosis was found in vivo, and the caspase-1 dependent pyroptosis was found in vitro. Silencing of NLRP3 in vivo did not attenuate systemic metabolic disturbances. However, NLRP3 gene silencing therapy ameliorated cardiac inflammation, pyroptosis, fibrosis and cardiac function. Silencing of NLRP3 in H9c2 cardiomyocytes suppressed pyroptosis under high glucose. ROS inhibition markedly decreased nuclear factor-kB (NF-kB) phosphorylation, thioredoxin interacting/inhibiting protein (TXNIP), NLRP3 inflammasome, and mature IL-1beta in high glucose treated H9c2 cells. Inhibition of NF-kB reduced the activation of NLRP3 inflammasome. TXNIP-siRNA decreased the activation of caspase-1 and IL 1beta. CONCLUSION: NLRP3 inflammasome contributed to the development of DCM. NF kappaB and TXNIP mediated the ROS-induced caspase-1 and IL-1beta activation, which are the effectors of NLRP3 inflammasome. NLRP3 gene silencing may exert a protective effect on DCM. PMID- 25136836 TI - Light scattering sensor for direct identification of colonies of Escherichia coli serogroups O26, O45, O103, O111, O121, O145 and O157. AB - BACKGROUND: Shiga-toxin producing Escherichia coli (STEC) have emerged as important foodborne pathogens, among which seven serogroups (O26, O45, O103, O111, O121, O145, O157) are most frequently implicated in human infection. The aim was to determine if a light scattering sensor can be used to rapidly identify the colonies of STEC serogroups on selective agar plates. METHODOLOGY/PRINCIPAL FINDINGS: Initially, a total of 37 STEC strains representing seven serovars were grown on four different selective agar media, including sorbitol MacConkey (SMAC), Rainbow Agar O157, BBL CHROMagarO157, and R&F E. coli O157:H7, as well as nonselective Brain Heart Infusion agar. The colonies were scanned by an automated light scattering sensor, known as BARDOT (BActerial Rapid Detection using Optical scattering Technology), to acquire scatter patterns of STEC serogroups, and the scatter patterns were analyzed using an image classifier. Among all of the selective media tested, both SMAC and Rainbow provided the best differentiation results allowing multi-class classification of all serovars with an average accuracy of more than 90% after 10-12 h of growth, even though the colony appearance was indistinguishable at that early stage of growth. SMAC was chosen for exhaustive scatter image library development, and 36 additional strains of O157:H7 and 11 non-O157 serovars were examined, with each serogroup producing unique differential scatter patterns. Colony scatter images were also tested with samples derived from pure and mixed cultures, as well as experimentally inoculated food samples. BARDOT accurately detected O157 and O26 serovars from a mixed culture and also from inoculated lettuce and ground beef (10-h broth enrichment +12-h on-plate incubation) in the presence of natural background microbiota in less than 24 h. CONCLUSIONS: BARDOT could potentially be used as a screening tool during isolation of the most important STEC serovars on selective agar plates from food samples in less than 24 h. PMID- 25136838 TI - Solvent-assisted electrospray ionization for direct analysis of various compounds (complex) from low/nonpolar solvents and eluents. AB - Electrospray ionization (ESI) is a powerful ionization technique with a wide range of applications. However, the analytes in low/nonpolar solvents cannot be analyzed directly in electrospray ionization-mass spectrometry (ESI-MS), because low/nonpolar solvents are incompatible with ESI, because of their low conductivity. To circumvent this problem, we introduce an electrospray-based ionization method termed solvent-assisted electrospray ionization (SAESI). With the help of electrospray solvents at the tip of the spray needle, compounds in "non-electrospray ionization-friendly" solvents can be ionized directly using solvent-assisted electrospray ionization-mass spectrometry (SAESI-MS). The key features that the assistant solvent can be chosen flexibly and makes little interference to samples lead to better ionization performance in detection of organic reaction intermediates and real-time analysis of polymers and chiral drugs separated by gel permeation chromatography (GPC) and normal phase liquid chromatography (NPLC). Furthermore, it can achieve online hydrogen/deuterium (H/D) exchange reaction and even mitigate the signal suppression caused by strong acid modifiers in liquid chromatography. In addition, all parts of this device are commercially available and it only requires two parameters to be optimized, which makes SAESI easy to handle. PMID- 25136837 TI - Metabolic characterization of adults with binge eating in the general population: the Framingham Heart Study. AB - OBJECTIVE: To describe the metabolic profile of individuals with objective binge eating (OBE) and to evaluate whether associations between OBE and metabolic risk factors are mediated by body mass index (BMI). METHODS: Participants from the Framingham Heart Study, Third Generation and Omni 2 cohorts (n = 3,551, 53.1% women, mean age 46.4 years) were screened for binge eating. Multivariable adjusted regression models to examine the associations of OBE with metabolic risk factors were used. RESULTS: The prevalence of OBE was 4.8% in women and 4.9% in men. Compared to non-binge eating, OBE was associated with higher odds of hypertension (OR 1.85, 95% CI 1.32-2.60), hypertriglyceridemia (OR 1.42, 95% CI 1.01-2.01), low HDL (OR 1.70, 95% CI 1.18-2.44), insulin resistance (OR 3.18, 95% CI 2.25-4.50) and metabolic syndrome (OR 2.75, 95% CI 1.94-3.90). Fasting glucose was 7.2 mg dl(-1) higher in those with OBE (P = 0.0001). Individuals with OBE had more visceral, subcutaneous and liver fat. Most of these associations were attenuated with adjustment for BMI, with the exception of fasting glucose. CONCLUSIONS: Binge eating is associated with a high burden of metabolic risk factors. Much of the associated risk appears to be mediated by BMI, with the exception of fasting glucose. PMID- 25136839 TI - Extracellular vesicles as a platform for 'liquid biopsy' in glioblastoma patients. AB - Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30-2000 nm in size. These vesicles are secreted by both normal and neoplastic cells. Physiologically, EVs serve multiple critical biologic functions, including cellular remodeling, intracellular communication, modulation of the tumor microenvironment and regulation of immune function. Because EVs contain genetic and proteomic contents that reflect the cell of origin, it is possible to detect tumor-specific material in EVs secreted by cancer cells. Importantly, EVs secreted by cancer cells transgress anatomic compartments and can be detected in the blood, cerebrospinal fluid, and other biofluids of cancer patients. In this context, there is a growing interest in analyzing EVs from the biofluid of cancer patients as a means of disease diagnosis and therapeutic monitoring. In this article, we review the development of EVs as a diagnostic platform for the most common form of brain cancer, glioblastoma, discuss potential clinical translational opportunities and identify the central challenges associated with future clinical applications. PMID- 25136841 TI - The diagnosis accuracy of PLA2R-AB in the diagnosis of idiopathic membranous nephropathy: a meta-analysis. AB - BACKGROUND: The presence of antibodies against the M-type phospholipase A2 receptor (PLA2R-AB) is considered to be a promising serological diagnostic biomarker of idiopathic membranous nephropathy (iMN). However, controversy remains about the diagnostic accuracy of serum PLA2R-AB testing. Here, we performed a comprehensive meta-analysis to assess the overall diagnostic value of serum PLA2R-AB testing in iMN detection. METHODS: PubMed, Embase, and CNKI (Chinese National Knowledge Infrastructure) were searched for relevant original articles through January 31, 2014. The summary sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) were estimated using the bivariate model. The heterogeneity among studies was explored by subgroup and meta-regression analysis. RESULTS: 9 articles, including 15 studies, were eventually identified with a total of 2212 patients. The summary sensitivity of all studies is 78% (95% CI: 66% to 87%) and the specificity is 99% (95% CI: 96% to 100%). The summary positive and negative likelihood ratios are 96.1 (95% CI, 19.5 to 472.1) and 0.22 (95% CI: 0.14 to 0.35), respectively. The DOR is 437 (95%CI, 74 to 2592). The subgroup analysis and meta-regression suggest the test interval is the main source of heterogeneity. CONCLUSIONS: Serum PLA2R AB testing is a useful tool to detect iMN. In addition, considering the high heterogeneity and potential publication bias, further high quality studies are needed in the future. PMID- 25136840 TI - The promise of methylation on beads for cancer detection and treatment. AB - Despite numerous technical hurdles, the realization of true personalized medicine is becoming a progressive reality for the future of patient care. With the development of new techniques and tools to measure the genetic signature of tumors, biomarkers are increasingly being used to detect occult tumors, determine the choice of treatment and predict outcomes. Methylation of CpG islands at the promoter region of genes is a particularly exciting biomarker as it is cancer specific. Older methods to detect methylation were cumbersome, operator-dependent and required large amounts of DNA. However, a newer technique called methylation on beads has resulted in a more uniform, streamlined and efficient assay. Furthermore, methylation on beads permits the extraction and processing of miniscule amounts of methylated tumor DNA in the peripheral blood. Such a technique may aid in the clinical detection and treatment of cancers in the future. PMID- 25136842 TI - Advanced disease at enrollment in HIV care in four sub-Saharan African countries: change from 2006 to 2011 and multilevel predictors in 2011. AB - OBJECTIVES: To examine changes between 2006 and 2011 in the proportion of HIV positive patients newly enrolled in HIV care with advanced disease and the median CD4 cell count at enrollment; and identify patient, facility, and contextual level factors associated with late enrollment in care in 2011. DESIGN: Cross sectional over time. METHODS: For time-trends analyses, routinely collected patient-level data (307 110 adults newly enrolled in 138 HIV clinical care facilities) in Kenya, Mozambique, Rwanda and Tanzania; and for analyses of correlates, patient-level data (46 201 in 195 facilities), and facility and population-level survey data were used. Late enrollment was defined as CD4 cell count 350 cells/MUl or less and/or WHO clinical stage 3/4. RESULTS: Late enrollment declined from 69.9 to 57.2% (P < 0.0001); median CD4 cell count increased from 242 to 292 cells/MUl (Ptrend < 0.0001). In 2011, risk of late enrollment was significantly higher for men and nonpregnant women vs. pregnant women; patients aged above 25 vs. 15-25 years; nonmarried vs. married; and those entering from sites other than prevention of mother-to-child transmission. More extensive HIV testing coverage in the region of a facility was significantly associated with lower risk of late enrollment. CONCLUSIONS: Despite improvement, in 2011, 57% of patients entered HIV care who were already antiretroviral therapy eligible. The lower risk of late enrollment among those referred from prevention of mother-to-child transmission and in regions where HIV testing coverage was higher suggests that innovative approaches to rapidly increase testing uptake among people living with HIV prior to the development of symptoms have the potential to reduce late enrollment in care. PMID- 25136844 TI - Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C reactive protein do not predict future allograft rejection in heart transplant recipients. AB - BACKGROUND: Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. METHODS: From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 +/- 4 (mean +/- standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. RESULTS: The mean age of the patients at HTx was 49 +/- 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ~ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0 12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13 52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90 2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. CONCLUSION: The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx. PMID- 25136843 TI - Satisfaction With Life Among Living Kidney Donors: A RELIVE Study of Long-Term Donor Outcomes. AB - BACKGROUND: Little is known about living kidney donors' satisfaction with life (SWL) after donation. We compared donors' SWL to previously reported general population samples and investigated predictors of donors' SWL. METHODS: Three transplant centers mailed questionnaires to assess SWL, physical health, optimism, retrospective evaluation of the donation experience, and demographic characteristics to living kidney donors' homes between 2010 and 2012. Two thousand four hundred fifty-five donors who were between 5 and 48 years from the time of their donor surgery completed the questionnaire. RESULTS: Eighty-four percent of donors were satisfied with their lives (scores >= 20 on the Satisfaction With Life Scale). Donors were at least as satisfied with their lives as previously reported general population samples. After adjusting for physical health, optimism, and demographics, donors' SWL was significantly associated with donors' recalled experience of donation. Social support and positive effects of the donation on relationships predicted greater SWL. Financial difficulties associated with donation and longer recovery times predicted lower SWL. Recipient outcomes were not significantly related to donor SWL. DISCUSSION: Limitations include the lack of predonation SWL data, potential bias in postdonation SWL because of the situational context of the questionnaire, and a sample that is not representative of all U.S. living kidney donors. Nonetheless, strategies focused on improving the donation experience, particularly related to recovery time, financial issues, and social support, may result in greater SWL after donation. PMID- 25136845 TI - Compensatory hypertrophy of the remaining kidney in medically complex living kidney donors over the long term. AB - BACKGROUND: The criteria for living kidney donation are changing, resulting in increased numbers of individuals with risk factors being accepted as donors. The long-term function and volume changes in the remaining kidney of these medically complex donors remain largely unknown. METHODS: Living kidney donors with three separate risk factors (older age, obesity, or hypertension) were reevaluated 5 years after donation. The function and volume of the remaining kidney were assessed and compared to those of standard donors. RESULTS: The body size correlated significantly with the kidney size and glomerular filtration rate (GFR) at the time of donation. Five years after donation, the remaining kidney size increased by a mean of 29.3%, and the GFR by 35.6%. The increase in GFR was uniform. In univariate analysis, neither the changes in the size nor the changes in the 1GFR were found to be associated with the risk factors. CONCLUSION: Medically complex living donors demonstrate similar compensatory increase in function and volume of the remaining kidney compared to standard donors, 5 years after donation. PMID- 25136846 TI - "Early" withdrawal of glucocorticosteroids is well tolerated by kidney transplant recipients without increasing allograft rejection while preserving bone integrity. PMID- 25136847 TI - Protective effect of neutralization of the extracellular high-mobility group box 1 on renal ischemia-reperfusion injury in miniature swine. AB - BACKGROUND: Strategies that reduce ischemia-reperfusion injury (IRI) have the potential to expand the numbers of available organs for transplantation. Recent reports in rodent models have demonstrated that high-mobility group box 1 (HMGB1) acts as an alarm in initiating the inflammatory response resulting from ischemic injury. The aim of this study was to evaluate the cytoprotective effects of anti HMGB1 antibodies on renal IRI in preclinical large animals. METHODS: One hundred twenty minutes of warm and 60 min of cold renal ischemia were induced in 8 CLAWN miniature swine. Three of eight animals received intravenous anti-HMGB1 antibody at 1 mg/kg just before the reperfusion of renal blood flow. Renal function was assessed by serum creatinine and renal biopsy. Serum levels of interleukin (IL) 1beta, IL-6, and HMGB1 were measured. RESULTS: The concentration of HMGB1 increased as early as 30 min after reperfusion and before the elevation of IL 1beta and IL-6. Serum creatinine levels were markedly elevated, peaking at a median of 5 days (peak creatinine levels: 11.6 +/- 1.6 mg/dL) and recovering by day 14. Anti-HMGB1 antibody injection dramatically decreased renal damage as well as serum levels of HMGB1 associated with IRI. Renal function returned to near normal by day 9, and peak creatinine levels were markedly lower (7.4 +/- 0.2 mg/dL), and biopsies possessed fewer pathologic changes when compared to the control group. CONCLUSION: In this study, we demonstrated the beneficial effects of perioperative administration of anti-HMGB1 antibody in reducing renal IRI in a clinically relevant, large animal model. PMID- 25136850 TI - Adherence to the 2010 American College of Cardiology Foundation Appropriate Use Criteria for Cardiac Computed Tomography: Quality Analysis at a Tertiary Referral Center. AB - BACKGROUND: In November 2010, the American College of Cardiology Foundation published revised appropriateness criteria (AC) for cardiac computed tomography (CT). We evaluated adherence to these criteria by providers of different subspecialties at a tertiary referral center. METHODS: Reports of 383 consecutive patients who underwent clinically indicated cardiac CT from December 1, 2010, to July 31, 2011, were reviewed by physicians with appropriate training in cardiac CT. Scans were classified as appropriate, inappropriate, or uncertain based on the revised 2010 AC. Studies that did not fall under any of the specified indications were labeled as unclassified. Adherence to the AC was also analyzed as a function of provider type. Research scans were excluded from this analysis. RESULTS: Three hundred eight exams (80%) were classified as appropriate; 26 (7%), as inappropriate; 30 (8%), as uncertain; and 19 (5%), as unclassified. Of the 19 (5%) unclassified cardiac CT exams, the most common indication was for evaluation of suspected aortic dissection. Three hundred five exams (80%) were referred by cardiologists; 73 (19%), by internists; and 5 (1%), by neurologists. Of the 305 cardiology-referred studies, 221 (73%) were ordered by general cardiologists; 28 (9%), by interventional cardiologists; and 56 (19%), by electrophysiologists. There was no significant difference in adherence to the criteria between provider specialties or between cardiology subspecialties (P > 0.05). CONCLUSIONS: high across provider specialties. PMID- 25136848 TI - Lymphocyte depletion after alemtuzumab induction disrupts intestinal fungal microbiota in cynomolgus monkeys. AB - BACKGROUND: The interactions of specific fungal phylotypes with immune cells have been recently documented; however, little is known whether gut fungal microbiota is influenced by aberrant immune response in immunosuppressive state. This study aimed to define the biologic impact of lymphocyte depletion on gut fungal microbiota and their relationship. METHODS: Fifteen male cynomolgus monkeys with CD52 antigen negative on erythrocytes were administered intravenously with a single dose (3.0 mg kg body weight) of alemtuzumab. Depletion and repopulation of circulating and mucosal lymphocytes were determined. The dynamic variations of intestinal fungal microbiota were characterized using 18S ribosomal DNA-based molecular techniques. RESULTS: The fungal microbiota in colonal mucosa was perturbed during lymphocyte depletion, characterized by increased diversity and colonization of Candida albicans, Aspergillus clavatus, and Saccharomyces cerevisiae. The diversity of the fecal fungal population decreased markedly after mucosal lymphocyte depletion, and specific fungal phylotypes, especially Candida albicans, Saccharomyces cerevisiae, and Botryotinia fuckeliana, were expanded (P<0.05). After reconstitution of mucosal lymphocytes, the composition and diversity of the gut fungal microbiota were both recovered. A close association of the community diversity and Candida albicans colonization with T lymphocyte subsets was also identified. CONCLUSION: Our findings demonstrate that mucosal lymphocyte depletion leads to the dysbiosis of gut fungal microbiota, suggesting its role in maintaining host-fungus homeostasis. The pathophysiologic consequences of this altered fungal colonization might provide novel clues to uncover the underlying mechanism of enteric fungal infection in immunosuppressive therapies. PMID- 25136849 TI - Polyomavirus nephropathy: quantitative urinary polyomavirus-Haufen testing accurately predicts the degree of intrarenal viral disease. AB - BACKGROUND: A qualitative highly predictive urinary test for polyomavirus nephropathy (PVN) is the PV-Haufen test. This article evaluates whether a quantitative PV-Haufen analysis, that is, the number of PV-Haufen shed per milliliter urine, predicts PVN disease grades and the severity of intrarenal PV replication. METHODS: Polyomavirus-Haufen were counted in 40 urine samples from patients with biopsy-proven definitive PVN. The number of PV-Haufen was correlated with both histologic PVN disease grades 1 to 3 and the number of SV40 T-expressing cells as indicators of intrarenal PV replication in corresponding renal allograft biopsies (manual counts and automated morphometry). Findings from quantitative PV-Haufen analyses were compared to conventional laboratory test results, that is, BK viremia (quantitative polymerase chain reaction [PCR]) and BK viruria (quantitative PCR and decoy cell counts). RESULTS: Polyomavirus-Haufen counts showed excellent correlation (alpha0.77-0.86) with the severity of intrarenal PV replication and disease grades. In particular, low PV-Haufen numbers strongly correlated with early PVN grade 1 and minimal intrarenal expression of SV40-T antigen (P < 0.001). In comparison, BK viremia and viruria levels by PCR showed only modest correlations with histologic SV40-T expression (alpha0.40-0.49) and no significant correlation with disease grades or minimal intrarenal PV replication. No correlations were seen with urinary decoy cell counts. In contrast to conventional quantitative PCR assays or decoy cell counts, quantitative urinary PV-Haufen testing accurately reflects the severity of PV replication, tissue injury, and PVN disease grades. CONCLUSIONS: Quantitative PV Haufen testing is a novel noninvasive approach to patient management for the diagnosis and prediction of PVN disease grades and monitoring of disease course during therapy. PMID- 25136851 TI - Physicians' Practice of Dispensing Medicines: A Qualitative Study. AB - OBJECTIVES: The physical act of giving medication to patients to administer away from a health care setting, dispensing, is normally performed by pharmacists. Dispensing of medication by physicians is a neglected patient safety issue, and having observed considerable variation in practice, the lead author sought to explore this issue further. A literature review yielded zero articles pertaining to this, so an exploratory study was commenced. The qualitative arm, relating to junior physicians' experience of, and training in, dispensing, is reported here. METHODS: Focus groups were conducted to explore the beliefs, ideas, and experiences of physicians-in-training pertaining to dispensing of medication. These were recorded and transcribed. The transcriptions were thematically analyzed using the grounded theory. RESULTS: The emergency department was the most common site of dispensing. No formal training in dispensing had been received. Informal training was variable in content and utility. The physicians felt that dispensing was part of their role. CONCLUSIONS: Despite being expected to dispense, and the patient safety issues involved in giving drugs to patients to use at home, physicians do not feel that they have been trained to undertake this task. These findings from 1 hospital raise questions about the wider quality and safety of this practice. PMID- 25136852 TI - Family Satisfaction in Critical Care Units: Does an Open Visiting Hours Policy Have an Impact? AB - : For critically ill patients, the interaction between health care providers and family members is essential in daily decision making. Improving this relationship has a positive impact on satisfaction with the overall care provided to patients and reduces family member symptoms of depression, anxiety, and posttraumatic stress disorder. In this study, we analyzed the impact of visitation policy (open versus restricted) on family satisfaction using the previously well-validated Critical Care Family Satisfaction Survey (CCFSS) questionnaire. METHODS: This is a cross-sectional prospective observational study conducted between November 1, 2009, and January 31, 2010, in 2 critical care units with 2 different visiting policy systems, unit A (open visiting hours) and B (restricted visiting hours), comparing family satisfaction in both units using the CCFSS questionnaire. Responses were grouped in 5 satisfaction constructs, namely, the support construct, which assesses the degree of satisfaction with the support of the intensive care staff as perceived by relatives; the assurance construct, which assesses the degree of satisfaction regarding honest answers being given and the responder's confidence that the patient is receiving the best care possible; the proximity construct, which assesses the degree of satisfaction with the physical and emotional access to the patient; the information construct, which assesses the degree of satisfaction with the adequacy of information given to relatives; and the comfort construct, which assesses satisfaction with physical comfort and amenities. RESULTS: During the study period, 115 questionnaires were distributed in each of the 2 sites. The response rates in units A and B were 92% (106) and 100% (115), respectively. The mean stay time in the intensive care unit was 3.7 days. There were more trauma cases in unit A and more cardiac patients in unit B. There was no significant difference between the 2 units in any of the 5 satisfaction constructs, the support, assurance, proximity, information, and comfort constructs, although there was a nonsignificant trend favoring the unit with the more liberal visit policy regarding amenities (unit A). CONCLUSIONS: We concluded that family satisfaction to care provided in intensive care as measured by the CCFSS questionnaire was not influenced by frequency of visitation among Saudi families. Factors other than open visiting hours may be important to evaluate. PMID- 25136854 TI - Conservation genetics of the Philippine tarsier: cryptic genetic variation restructures conservation priorities for an island archipelago primate. AB - Establishment of conservation priorities for primates is a particular concern in the island archipelagos of Southeast Asia, where rates of habitat destruction are among the highest in the world. Conservation programs require knowledge of taxonomic diversity to ensure success. The Philippine tarsier is a flagship species that promotes environmental awareness and a thriving ecotourism economy in the Philippines. However, assessment of its conservation status has been impeded by taxonomic uncertainty, a paucity of field studies, and a lack of vouchered specimens and genetic samples available for study in biodiversity repositories. Consequently, conservation priorities are unclear. In this study we use mitochondrial and nuclear DNA to empirically infer geographic partitioning of genetic variation and to identify evolutionarily distinct lineages for conservation action. The distribution of Philippine tarsier genetic diversity is neither congruent with expectations based on biogeographical patterns documented in other Philippine vertebrates, nor does it agree with the most recent Philippine tarsier taxonomic arrangement. We identify three principal evolutionary lineages that do not correspond to the currently recognized subspecies, highlight the discovery of a novel cryptic and range-restricted subcenter of genetic variation in an unanticipated part of the archipelago, and identify additional geographically structured genetic variation that should be the focus of future studies and conservation action. Conservation of this flagship species necessitates establishment of protected areas and targeted conservation programs within the range of each genetically distinct variant of the Philippine tarsier. PMID- 25136856 TI - Short- and long-term effects of ambient ozone and fine particulate matter on the respiratory health of chronic obstructive pulmonary disease subjects. AB - To date, no study has evaluated the short- and long-term effects air pollution exposure on emphysematous subjects who have undergone lung volume reduction surgery (LVRS). Data from the National Emphysema Treatment Trial study (1998 2003) included 1,218 subjects, aged 39 to 84. Daily values of ambient fine particulate matter (aerodynamic diameter < 2.5 MUm; PM2.5) and ozone were obtained. Mixed-effects models tested the association between short- and long term pollutant concentrations and changes in pulmonary function. Cumulative air pollution exposure was strongly associated with worsened respiratory function and symptoms. Mean PM2.5 was associated with poorer lung function. Lagged exposures were poorly associated with respiratory health outcomes. There were detrimental respiratory and pulmonary effects observed in response to even low levels of ambient air pollutants among study participants. These results are indicative that exposures even below those of air quality standards may still pose significant risks to severe chronic obstructive pulmonary disease (COPD) subjects. PMID- 25136855 TI - A canonical circuit for generating phase-amplitude coupling. AB - 'Phase amplitude coupling' (PAC) in oscillatory neural activity describes a phenomenon whereby the amplitude of higher frequency activity is modulated by the phase of lower frequency activity. Such coupled oscillatory activity--also referred to as 'cross-frequency coupling' or 'nested rhythms'--has been shown to occur in a number of brain regions and at behaviorally relevant time points during cognitive tasks; this suggests functional relevance, but the circuit mechanisms of PAC generation remain unclear. In this paper we present a model of a canonical circuit for generating PAC activity, showing how interconnected excitatory and inhibitory neural populations can be periodically shifted in to and out of oscillatory firing patterns by afferent drive, hence generating higher frequency oscillations phase-locked to a lower frequency, oscillating input signal. Since many brain regions contain mutually connected excitatory-inhibitory populations receiving oscillatory input, the simplicity of the mechanism generating PAC in such networks may explain the ubiquity of PAC across diverse neural systems and behaviors. Analytic treatment of this circuit as a nonlinear dynamical system demonstrates how connection strengths and inputs to the populations can be varied in order to change the extent and nature of PAC activity, importantly which phase of the lower frequency rhythm the higher frequency activity is locked to. Consequently, this model can inform attempts to associate distinct types of PAC with different network topologies and physiologies in real data. PMID- 25136859 TI - Amino acid-based zwitterionic polymers: antifouling properties and low cytotoxicity. AB - A group of five amino acid containing zwitterionic vinyl monomers, based on serine, lysine, ornithine, glutamic acid, and aspartic acid, respectively, were proposed and developed for potential antifouling applications. Their polymer brushes were grafted on gold chips by surface-initiated photoiniferter-mediated polymerization. We then compared their performance in resisting protein adsorption from full human serum and plasma. All five polymers can reduce protein adsorption by more than 90% compared to the unmodified gold. The ornithine-based and aspartic acid-based poly(methacrylamide) can most strongly resist protein adsorption from serum and plasma, compared to the other three. The ability of surfaces to suppress bacterial adhesion is another criterion in evaluating antifouling properties of materials. Our results show that the five polymer grafted surfaces can significantly suppress Escherichia coli K12 adhesion to 99% compared to the bare gold surface. The zwitterionic structure of amino acids, with homogenously distributed and balanced positive and negative charges, is responsible for the outstanding antifouling properties. Considering multiple potential applications (e.g. medical devices and drug delivery) of the antifouling materials, we further systematically evaluated the cytotoxicity of both monomers and polymer nanogels for all five materials at various concentrations. Very low cytotoxicity was observed for all tested amino acid based monomers and nanogels, which is comparable or even lower than the traditional and some newly developed antifouling materials, which might be related to the biomimetic nature of amino acids. PMID- 25136857 TI - Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation. AB - Elevated levels of erythrocyte-derived microparticles are present in the circulation in medical conditions affecting the red blood cells. Erythrocyte derived microparticles expose phosphatidylserine thus providing a suitable surface for procoagulant reactions leading to thrombin formation via the tenase and prothrombinase complexes. Patients with elevated levels of circulating erythrocyte-derived microparticles have increased thrombin generation in vivo. The aim of the present study was to investigate whether erythrocyte-derived microparticles are able to support the anticoagulant reactions of the protein C system. Erythrocyte-derived microparticles were isolated using ultracentrifugation after incubation of freshly prepared erythrocytes with the ionophore A23187 or from outdated erythrocyte concentrates, the different microparticles preparations yielding similar results. According to flow cytometry analysis, the microparticles exposed phoshatidylserine and bound lactadherin, annexin V, and protein S, which is a cofactor to activated protein C. The microparticles were able to assemble the tenase and prothrombinase complexes and to stimulate the formation of thrombin in plasma-based thrombin generation assay both in presence and absence of added tissue factor. The addition of activated protein C in the thrombin generation assay inhibited thrombin generation in a dose-dependent fashion. The anticoagulant effect of activated protein C in the thrombin generation assay was inhibited by a monoclonal antibody that prevents binding of protein S to microparticles and also attenuated by anti-TFPI antibodies. In the presence of erythrocyte-derived microparticles, activated protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas efficient inhibition of FVIIIa depended on the synergistic cofactor activity of protein S and FV. In summary, the erythrocyte-derived microparticle surface is suitable for the anticoagulant reactions of the protein C system, which may be important to balance the initiation and propagation of coagulation in vivo. PMID- 25136860 TI - Chemically modified peptide scaffolds target the CFTR-associated ligand PDZ domain. AB - PDZ domains are protein-protein interaction modules that coordinate multiple signaling and trafficking pathways in the cell and that include active therapeutic targets for diseases such as cancer, cystic fibrosis, and addiction. Our previous work characterized a PDZ interaction that restricts the apical membrane half-life of the cystic fibrosis transmembrane conductance regulator (CFTR). Using iterative cycles of peptide-array and solution-binding analysis, we targeted the PDZ domain of the CFTR-Associated Ligand (CAL), and showed that an engineered peptide inhibitor rescues cell-surface expression of the most common CFTR disease mutation DeltaF508. Here, we present a series of scaffolds containing chemically modifiable side chains at all non-motif positions along the CAL PDZ domain binding cleft. Concordant equilibrium dissociation constants were determined in parallel by fluorescence polarization, isothermal titration calorimetry, and surface plasmon resonance techniques, confirming robust affinity for each scaffold and revealing an enthalpically driven mode of inhibitor binding. Structural studies demonstrate a conserved binding mode for each peptide, opening the possibility of combinatorial modification. Finally, we diversified one of our peptide scaffolds with halogenated substituents that yielded modest increases in binding affinity. Overall, this work validates our approach and provides a stereochemical foundation for further CAL inhibitor design and screening. PMID- 25136861 TI - Ire1 mediated mRNA splicing in a C-terminus deletion mutant of Drosophila Xbp1. AB - The Unfolded Protein Response is a homeostatic mechanism that permits eukaryotic cells to cope with Endoplasmic Reticulum (ER) stress caused by excessive accumulation of misfolded proteins in the ER lumen. The more conserved branch of the UPR relies on an ER transmembrane enzyme, Ire1, which, upon ER stress, promotes the unconventional splicing of a small intron from the mRNA encoding the transcription factor Xbp1. In mammals, two specific regions (the hydrophobic region 2--HR2--and the C-terminal translational pausing site) present in the Xbp1unspliced protein mediate the recruitment of the Xbp1 mRNA-ribosome-nascent chain complex to the ER membrane, so that Xbp1 mRNA can be spliced by Ire1. Here, we generated a Drosophila Xbp1 deletion mutant (Excision101) lacking both HR2 and C-terminal region, but not the Ire1 splicing site. We show that Ire1-dependent splicing of Xbp1 mRNA is reduced, but not abolished in Excision101. Our results suggest the existence of additional mechanisms for ER membrane targeting of Xbp1 mRNA that are independent of the C-terminal domain of Drosophila Xbp1unspliced. PMID- 25136862 TI - MicroRNA-410 suppresses migration and invasion by targeting MDM2 in gastric cancer. AB - Gastric cancer is one of the most frequent malignancies in tumors in the East Asian countries. Identifying precise prognostic markers and effective therapeutic targets is important in the treatment of gastric cancer. microRNAs (miRNAs) play important roles in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In this study, we found that the levels of miR-410 in gastric cancer and cell lines were much lower than that in the normal control, respectively, and the lower level of miR-410 was significantly associated with lymph-node metastasis. Transfection of miR-410 mimics could significantly inhibit the cell proliferation, migration and invasion in the HGC-27 gastric cancer cell lines. In contrast, knockdown of miR-410 had the opposite effect on the cell proliferation, migration and invasion. Moreover, we also found that MDM2 was negatively regulated by miR-410 at the post transcriptional level, via a specific target site with the 3'UTR by luciferase reporter assay. The expression of MDM2 was inversely correlated with miR-410 expression in gastric cancer tissues, and overexpression of MDM2 in miR-410 transfected gastric cancer cells effectively rescued the inhibition of cell proliferation and invasion caused by miR-410. Thus, our findings suggested that miR-410 acted as a new tumor suppressor by targeting the MDM2 gene and inhibiting gastric cancer cells proliferation, migration and invasion. The findings of this study contributed to the current understanding of these functions of miR-410 in gastric cancer. PMID- 25136863 TI - Superior laryngeal nerve injury: effects, clinical findings, prognosis, and management options. AB - PURPOSE OF REVIEW: The superior laryngeal nerve (SLN) provides motor innervation to the cricothyroid muscle. However, the functions of this muscle and the anatomic variations of the nerve that supplies it are not fully understood. SLN paresis and paralysis (SLNp) is difficult to diagnose because of a lack of consistent laryngeal findings, and its effects on the voice likely go beyond simple pitch elevation control. RECENT FINDINGS: Although SLNp has traditionally been thought to lead to voice pitch limitation, recent research findings reveal multiple roles for this nerve in voice and speech. Cricothyroid muscles are the primary controls of fundamental frequency of voice. SLNp can lead to significant contraction of pitch range, vocal fold vibratory phase asymmetry, and acoustic aperiodicity, thus leading to an overall poor vocal quality. In addition, cricothyroid muscles may also play a role in pitch lowering and shifting from voiced to unvoiced sounds during speech. SUMMARY: Subtle signs, symptoms, and diagnostic findings associated with SLNp make this disorder difficult to characterize clinically. Lack of treatment methodologies to restore the dynamic action of the cricothyroid muscles poses difficulties in treating patients with this condition. A more thorough understanding of the effects of SLNp will improve diagnosis and treatment. PMID- 25136865 TI - A perspective on the evolution of distal radius fracture treatment. PMID- 25136866 TI - En bloc joystick reduction of a comminuted intra-articular distal radius fracture: a technical trick. AB - A patient with a 1-month-old intra-articular distal radius fracture (treated closed in a splint) presented with an unacceptable degree of pain and stiffness caused by shortening and dorsal angulation of the distal radius. The fracture was comminuted with 4 or 5 distinct fragments, several involving the articular surface. Surgical correction was attempted. During the procedure, it was noted that, though the distal radius was shortened and angulated, there was actually acceptable congruity of the articular surface itself, despite the intra-articular nature of the fracture. Bone quality was poor and healing incomplete. Thus, we were concerned the currently congruous articular surface would fall apart with manipulation. Given this situation, we used a unique scaffolding technique with Kirschner wires placed in perpendicular fashion to both hold the articular surface intact and manipulate it en bloc. This technique is a simple way to turn a complex fracture into an easily reduced 2-part fracture. PMID- 25136864 TI - In vitro inflammation inhibition model based on semi-continuous toll-like receptor biosensing. AB - A chemical inhibition model of inflammation is proposed by semi-continuous monitoring the density of toll-like receptor 1 (TLR1) expressed on mammalian cells following bacterial infection to investigate an in vivo-mimicked drug screening system. The inflammation was induced by adding bacterial lysate (e.g., Pseudomonas aeruginosa) to a mammalian cell culture (e.g., A549 cell line). The TLR1 density on the same cells was immunochemically monitored up to three cycles under optimized cyclic bacterial stimulation-and-restoration conditions. The assay was carried out by adopting a cell-compatible immunoanalytical procedure and signal generation method. Signal intensity relative to the background control obtained without stimulation was employed to plot the standard curve for inflammation. To suppress the inflammatory response, sodium salicylate, which inhibits nuclear factor-kappaB activity, was used to prepare the standard curve for anti-inflammation. Such measurement of differential TLR densities was used as a biosensing approach discriminating the anti-inflammatory substance from the non effector, which was simulated by using caffeic acid phenethyl ester and acetaminophen as the two components, respectively. As the same cells exposed to repetitive bacterial stimulation were semi-continuously monitored, the efficacy and toxicity of the inhibitors may further be determined regarding persistency against time. Therefore, this semi-continuous biosensing model could be appropriate as a substitute for animal-based experimentation during drug screening prior to pre-clinical tests. PMID- 25136867 TI - Volar plate capsulodesis for metacarpophalangeal hyperextension with basal joint arthritis. AB - Basal joint arthritis leads to thumb metacarpophalangeal (MCP) hyperextension that may prevent physiologic pinch. Various techniques have been used to address this hyperextension, but most are technically challenging, time-consuming, and not supported by long-term follow-up results. Furthermore, few groups have reported subjective, patient-based outcomes after such procedures. In a retrospective study, we evaluated a cohort of 14 patients who underwent a novel technique of thumb MCP capsulodesis in conjunction with basal joint arthroplasty. A mean of 4.74 years after surgery, subjective outcome measures (Disabilities of the Arm, Shoulder, and Hand questionnaire; visual analog scale for pain; patient satisfaction) and objective outcome measures (range of motion, grip and pinch strengths) all reflected excellent function. The described technique for MCP capsulodesis is an attractive adjunct to basal joint arthroplasty, but further prospective studies are needed to establish specific operative indications. PMID- 25136868 TI - Online ratings of orthopedic surgeons: analysis of 2185 reviews. AB - Online ratings of orthopedic surgeons have not been studied. We conducted a study to evaluate the online ratings of orthopedic surgeons in a major metropolitan region, to identify trends in ratings of orthopedic surgeons, and to analyze ratings to identify variables of significance in determining overall rating. Website traffic was used to identify the 8 busiest physician rating websites: AngiesList.com, EverydayHealth.com, Thirdage.com, Yelp.com, HealthGrades.com, Vitals.com, UCompareHealthcare.com, and RateMDs.com. These websites were consulted for data regarding orthopedic surgeons in a major metropolitan region with a population of 1.3 million in September 2012. Surgeon ratings were scaled from 0 to 100 for homogeneity. Of the 8 websites considered, 4 were excluded because of inaccessible or unreliable data. The qualifying sites were HealthGrades.com, Vitals.com, UCompareHealthcare.com, and RateMDs.com, with 2185 reviews total. Across these websites, mean overall rating of orthopedic surgeons was 81.8 (between 100, definitely recommend, and 80, mostly recommend). Five variables were statistically significant (Ps < .01) for higher ratings: ease of scheduling, time spent with patient, wait time, surgeon proficiency/knowledge, and bedside manner. PMID- 25136869 TI - Arthroscopic anterior shoulder stabilization with percutaneous assistance and posteroinferior capsular plication. AB - To study the technique and clinical outcomes of arthroscopic shoulder stabilization with anterior labral repair and percutaneous posteroinferior capsular plication, we retrospectively reviewed 20 cases. Mean (SD) final postoperative follow-up was 3.4 (0.6) years (range, 2.7-5.1 years). A mean (SD) of 4.9 (0.9) suture anchors (range, 4-7) was used during surgery, with 1.6 (0.7) (range, 1-3) devoted to the posteroinferior plication. There were statistically significant improvements in forward elevation (P = .016) and internal rotation (P = .018) from before surgery to final postoperative follow-up; external rotation did not change (P = .336). Significant improvements (P < .001) were also seen in visual analog scale pain ratings, American Shoulder and Elbow Surgeons survey scores, and Simple Shoulder Test scores. Mean (SD) Rowe instability score at final follow-up was 81.1 (28.9). Eighty-five percent of the patients returned to sport at or above preinjury level, and 70% returned to a degree of athletic physical contact at or above preinjury level. Two cases (10%) were categorized as treatment failures (redislocation). Percutaneously assisted arthroscopic anterior stabilization with posteroinferior capsular plication produces acceptable results, with functional outcomes and redislocation rates comparable to those reported in the literature. PMID- 25136870 TI - The normal patella--does it exist? A histologic analysis. AB - It is unclear if healthy-appearing patellae in patients having total knee arthroplasty (TKA) can be selectively retained. In the study reported here, we hypothesized that grossly normal-appearing patellae in TKA candidates would show significant evidence of microscopic degeneration and thinning of the articular cartilage. Ninety-six consecutive patients (110 knees) with primary degenerative osteoarthritis were recruited from a single institution between November 2010 and June 2011. Thirteen patellae (11 patients) had grossly normal-appearing cartilage. A pathologist measured patellar cartilage thickness in each quadrant and evaluated for evidence of microscopic degenerative change. Mean cartilage thickness was 2.35 mm (range, 1.0-3.0 mm) for superomedial quadrant, 2.31 mm (range, 1.5-3.0 mm) for superolateral quadrant, 2.31 mm (range, 1.0-4.0 mm) for inferomedial quadrant, and 2.62 mm (range, 1.5-3.5 mm) for inferolateral quadrant. Four-point mean (SD) was 2.39 (0.79) mm. Each patella demonstrated at least 2 of the predefined histologic markers of degeneration: fibrillation, fibrosis, chondrocyte proliferation, cyst formation, and fissuring and/or thinning. Even healthy-appearing patellae on gross examination have clear histologic markers of early to moderate articular degeneration. Further comparisons of cartilage thickness using area measurements are needed before the significance of the effect of this deterioration on the technique of selective patellar retention during TKA can be known. PMID- 25136871 TI - Nonaccidental traumatic dislocation of the hip in a 3-year-old child: a report of a rare pediatric injury. AB - Traumatic hip dislocations are rare in children, and reports of these injuries focus primarily on the risk of osteonecrosis of the femoral head as well as the long-term efficacy of treatment. Anatomical characteristics of the hip in young children, such as ligamentous laxity and a pliable acetabulum, can allow hip dislocation with low-energy trauma, but these injuries occur primarily in school aged children during play activities. We report a hip dislocation in a 3-year-old child with no clear explanation of the mechanism of injury and with multiple unexplained bruises at different stages of healing that led to the diagnosis of nonaccidental trauma (NAT). This case highlights the need to consider NAT in young patients with a traumatic hip dislocation. PMID- 25136872 TI - Snapping knee caused by symptomatic fabella in a native knee. AB - We report a case of a 31-year-old man with a 5-year history of snapping knee syndrome secondary to a single, large symptomatic fabella of the knee. On physical examination, the patient was able to reproduce an audible and palpable snapping with active range of motion. His condition was refractory to physical therapy. He had undergone a prior iliotibial band release at an outside facility. After excision of the fabella, measuring 15 * 8 * 9 mm, the patient's snapping and pain with activity were resolved. PMID- 25136873 TI - Effects of corticosteroid injection on nerve conduction testing for the diagnosis of carpal tunnel syndrome. AB - We conducted a study to determine the change in nerve conduction testing after steroid injection in patients with carpal tunnel syndrome (CTS). One hundred forty-five patients with suspected CTS were targeted for this study. Twenty-seven patients underwent testing before and after injection. Repeat studies were performed 4 to 6 weeks after injection. All data from the electrodiagnostic studies were entered into a database and used for comparison. Before injection, mean (SD) distal motor latency (DML) was 5.01 (0.9) ms, and mean (SD) peak sensory latency (PSL) was 5.01 (0.88) ms. After injection, mean (SD) DML was 4.82 (0.7) ms, and mean (SD) PSL was 4.69 (0.66) ms. Mean (SD) difference between preinjection and postinjection DML was 0.187 (0.45) ms, and mean difference between preinjection and postinjection PSL was 0.319 (0.48) ms. Both differences were statistically significant (paired t test). Our study results showed a statistical difference between testing done before and after steroid injection. These results indicate that injections given before electrodiagnostic testing alter results and may affect patient management. PMID- 25136874 TI - Critical review of patient education materials from the American Academy of Orthopaedic Surgeons. AB - We performed an expanded readability analysis to determine if the American Academy of Orthopaedic Surgeons, AAOS, had sufficiently improved its patient education materials since they were originally studied in 2007. In March 2013, we downloaded patient education materials from the AAOS patient information website, Your Orthopaedic Connection. Using 10 different readability formulas, we found that the mean grade level of patient education materials on the website is 8.84. Flesch-Kincaid analysis showed a mean grade level of 9.98, range, 6.6-12.6. Nine other readability analyses showed a mean reading level of 7.7, range, 6.5-13.7. Although this is an improvement over the 2007 level, it is above the average national reading comprehension level. The readability of patient education materials on the AAOS website still exceeds the average reading ability of a US adult. Revisions made over the 5 years leading up to this latest study resulted in better readability. The Prevention and Safety entries, written near seventh grade level, should serve as a model for the remaining articles. PMID- 25136875 TI - Do practice settings influence defensive medicine in orthopedic surgery? AB - Defensive medicine is often practiced out of fear of legal liability. We conducted a study to compare the costs of defensive medicine among US orthopedic surgeons by practice type and American Medical Association (AMA) state medical liability classification. Two thousand surgeons registered with the American Academy of Orthopaedic Surgeons were sent a survey on defensive medicine. Costs were analyzed using 2011 Centers for Medicare and Medicaid Services data. Of the 2000 surgeons, 1214 (61%) completed the survey. Results showed that defensive tests were ordered by a higher proportion of nonacademic physicians than academic physicians in all 8 categories of orthopedic care, with a mean difference of $2348 in monthly defensive expenditures between groups. A higher rate of defensive testing by orthopedists in AMA crisis states versus safe states was also observed in 6 of the 8 areas of care studied, with mean monthly defensive expenditures ranging from $9208 in crisis states to $6596 in safe states. Defensive orthopedics contributes significantly to health care costs, with marginal benefit to patients-especially in nonacademic and crisis-state orthopedics practices. PMID- 25136876 TI - Disseminated coccidioidomycosis of the spine in an immunocompetent patient. AB - Coccidioidomycosis infections result from inhalation of the dimorphic fungus Coccidiodes immitis. Coccidioidomycosis typically is benign, but its extremely rare disseminated form can result in significant morbidity and mortality. Dissemination of the fungus to the spine is difficult to control and usually requires an aggressive combination approach (surgical/medical). In this article, we report the case of a 27-year-old Indonesian man with vertebral osteomyelitis caused by disseminated coccidioidomycosis. We outline the case management (includes 30-month follow-up) and review the treatment recommendations. The patient presented with an unstable C5 pathologic fracture caused by C immitis. After corpectomy and stabilization of the cervical spine along with antifungal therapy with amphotericin B and oral fluconazole, he developed multiple complications. This case illustrates some of the potential pitfalls in managing spinal osteomyelitis caused by C immitis and the need for continuous medical therapy after surgical treatment. PMID- 25136877 TI - Bladder tear during revision total hip arthroplasty. AB - Total hip arthroplasty (THA) and revision total hip arthroplasty are among the most commonly performed orthopedic procedures. There are many reported complications of THA, but intrapelvic complications are a rare subset. Bladder injuries have infrequently been described in association with this common procedure. We present an unusual case of a bladder tear occurring intraoperatively during a revision THA. It is suspected that the patient's history of multiple prior hip procedures caused adhesions of the bladder to the pelvic floor and predisposed the bladder to injury during acetabular revision. Previous reports of bladder injury relating to THA have described thermal necrosis, component migration, and occasional direct perforation. There are no prior case reports describing bladder tears related to adhesions occurring intraoperatively during revision THA. This case report highlights the importance of surgeon awareness of an unusual complication. In this case, intraoperative and postoperative recognition of a hematuria diagnosis led to the appropriate treatment, and this patient had an acceptable outcome. PMID- 25136878 TI - The business side of medicine for orthopedic residents and fellows: when were we supposed to learn this? AB - CPT, CMS, RAC, ICD-10, ACA, RVU, ACO-these are a few of the 3-letter acronyms I find myself swimming in while completing my final years of orthopedic training. It has suddenly become clear that this aspect of my future career, the business side, has lacked appropriate preparation. From countless hours buried in textbooks as a first-year medical student to late nights in the operating room as a fellow, I realize that I have had no formal business training, not even a single course, while nearing the completion of, effectively, the 28th grade. All while just days away from running my own business-my clinical practice as an orthopedic surgeon. PMID- 25136879 TI - Cystatin C and risk of mortality among patients undergoing percutaneous coronary intervention. AB - AIMS: We tested the prognostic value of cystatin C in patients with documented coronary artery disease (CAD) who underwent percutaneous coronary artery intervention (PCI). We also tested the hypothesis that the incremental predictive value of cystatin C on all-cause mortality was superior to that of glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) formula. METHODS AND RESULTS: Included in the study were 2,757 patients (mean age 63 years, 77% men). Blood samples for cystatin C levels were collected immediately before PCI. During a median follow-up of two years, 114 patients died. In multivariable Cox analyses, after adjustment for several confounders, GFR (p=0.004) and cystatin C concentration (p<0.0001) were independent predictors of all-cause death. Cystatin C predicted all-cause death (c-statistic: 0.794) better than GFR estimate based on creatinine (c-statistic: 0.776, p=0.008 for comparison), and significantly reclassified 15% of patients into categories that reflected their actual likelihood of death more accurately (p=0.005). Adding cystatin C and GFR in the same multivariable survival model, only cystatin C level was a significant predictor of death. CONCLUSIONS: This study presents for the first time the incremental predictive value of cystatin C over the creatinine based MDRD formula on all-cause mortality for CAD patients undergoing PCI. PMID- 25136880 TI - Impact of frailty on short- and long-term morbidity and mortality after transcatheter aortic valve implantation: risk assessment by Katz Index of activities of daily living. AB - AIMS: Transcatheter aortic valve implantation (TAVI) represents a less invasive treatment option for elderly patients. Therefore, we aimed to determine the impact of frailty measured by the Katz Index of activities of daily living (ADL) on short- and long-term mortality after TAVI. METHODS AND RESULTS: Our study included 300 consecutive patients (mean age, 82+/-5 years) who had undergone TAVI at our institution (158 transapical, 142 transfemoral procedures). At baseline, 144 patients were impaired in at least one ADL and therefore defined as frail (Katz Index <6). Regarding in-hospital outcome, all serious complications except for stage 3 acute kidney injury were equally distributed in both groups, but early mortality was significantly higher in frail persons (5.5% vs. 1.3%, p=0.04 for immediate procedural mortality; 17% vs. 5.8%, p=0.002 for 30-day mortality; and 23% vs. 6.4%, p<0.0001 for procedural mortality). The risk-score-based 30-day mortality estimates (29% vs. 24% for log. EuroSCORE I, 9.5% vs. 7.5% for EuroSCORE II, and 8.8% vs. 5.9% for STS score) reflected neither the observed 30 day mortality in both groups nor the threefold risk elevation in frail patients. In contrast, the Katz Index <6 was identified as a significant independent predictor of long-term all-cause mortality by multivariate analysis (HR 2.67 [95% CI: 1.7-4.3], p<0.0001). During follow-up (median observation period 537 days) 56% of frail vs. 24% of non-frail patients died. CONCLUSIONS: Frailty status measured by the Katz Index represents a powerful predictor of adverse early and late outcome after TAVI, whereas commonly used risk scores lack calibration and discrimination in a TAVI-specific patient cohort. Therefore, we propose the incorporation of this simple and reproducible measure into pre-TAVI risk assessment. PMID- 25136881 TI - Immediate multivessel percutaneous coronary intervention versus culprit lesion intervention in patients with acute myocardial infarction complicated by cardiogenic shock: results of the ALKK-PCI registry. AB - AIMS: Current guidelines recommend immediate multivessel percutaneous coronary intervention (PCI) in patients with cardiogenic shock, despite the lack of randomised trials. We sought to investigate the use and impact on outcome of multivessel PCI in current practice in cardiogenic shock in Germany. METHODS AND RESULTS: Between January 2008 and December 2011 a total of 735 consecutive patients with acute myocardial infarction, cardiogenic shock and multivessel coronary artery disease underwent immediate PCI in 41 hospitals in Germany. Of these, 173 (23.5%) patients were treated with immediate multivessel PCI. The acute success of PCI with respect to TIMI 3 flow did not differ between the groups (82.5% versus 79.6%). In-hospital mortality with multivessel PCI and culprit lesion PCI was 46.8% and 35.8%, respectively. In multivariate analysis multivessel PCI was associated with an increased mortality (odds ratio 1.5; 95% confidence interval 1.15-1.84). CONCLUSIONS: In current clinical practice in Germany multivessel PCI is used only in one quarter of patients with cardiogenic shock treated with primary PCI. We observed an adverse effect of immediate multivessel PCI. Therefore, a randomised trial is needed to determine the definitive role of multivessel PCI in cardiogenic shock. PMID- 25136882 TI - Prognostic impact of multivessel versus culprit vessel only percutaneous intervention for patients with multivessel coronary artery disease presenting with acute coronary syndrome. AB - AIMS: To determine whether multivessel (MV) percutaneous coronary intervention (PCI) performed in one procedure improves outcomes when compared to single-vessel (SV) PCI for the culprit lesion(s) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS AND RESULTS: We utilised the Acute Catheterisation and Urgent Intervention Triage StrategY (ACUITY) study database to analyse the outcomes of 2,255 patients with MV disease who underwent SV PCI compared to 609 patients who underwent MV PCI in the setting of NSTE-ACS. The primary endpoint was the one-year rate of major adverse cardiac events (MACE): death from any cause, myocardial infarction (MI), or ischaemia-driven revascularisation. At one year, patients undergoing MV PCI compared to SV PCI had similar rates of MACE (24.1% vs. 21.7%, respectively, p=0.11). However, death/MI was significantly higher in the MV PCI group (15.7% vs. 12.6%, p=0.05), primarily driven by higher rates of periprocedural non-Q-wave MI. Rates of death, ischaemia driven revascularisation, stent thrombosis, acute renal failure and major bleeding were similar in both groups. By multivariable analysis with propensity score adjustment, MV PCI was not an independent predictor of one-year MACE (HR=1.22; 95% confidence interval [CI]: 0.96, 1.55; p=0.12) or death/MI (HR=1.28; 95% CI: 0.95, 1.74; p=0.15). CONCLUSIONS: In patients with NSTE-ACS and MV disease, MV PCI does not appear to provide a clear clinical benefit over SV PCI. Randomised clinical trials specifically addressing these two strategies in this population, with attention to quality of life and symptom relief, are warranted. PMID- 25136883 TI - A first-in-man clinical evaluation of Ultimaster, a new drug-eluting coronary stent system: CENTURY study. AB - AIMS: To report the six-month angiographic and two-year clinical outcome data from the first-in-man study with the Ultimaster DES, a thin-strut cobalt-chromium sirolimus-eluting stent (SES) with an innovative abluminal-gradient-coated bioresorbable polymer. METHODS AND RESULTS: CENTURY is a multicentre, single-arm, prospective study that enrolled 105 patients (113 lesions) with coronary artery disease. All patients were scheduled to have an angiographic follow-up at six months, while 45 and 20 patients respectively had IVUS and OCT assessments. The primary endpoint was six-month in-stent late lumen loss. Secondary endpoints included clinical, IVUS and OCT outcomes. Clinical follow-up is available up to two years and will continue up to five years. Procedural success was 97.1% and device success was 100%. Angiographic late loss at six months was 0.04+/-0.35 mm, also reflected in a low binary restenosis rate of 0.9% and confirmed by IVUS assessed neointimal volume obstruction of 1.02+/-1.62%. The mean strut coverage assessed by OCT was 96.2% with 1.66+/-4.02 malapposed stent struts. There were no deaths in the study, three (2.9%) periprocedural and one (0.9%) spontaneous myocardial infarction, not related to the target vessel. At one and two years, the target lesion failure rate was 3.8% and 5.7%, while the TLR rate was 1.9% and 2.8%, respectively. There was one acute definite stent thrombosis. CONCLUSIONS: The UltimasterTM novel bioresorbable polymer sirolimus-eluting stent demonstrated good performance, including high procedural success and strong suppression of neointimal proliferation at six months. Good safety and effectiveness were shown up to two years in the studied population. PMID- 25136884 TI - Three-year clinical outcome in the Primary Stenting of Totally Occluded Native Coronary Arteries III (PRISON III) trial: a randomised comparison between sirolimus-eluting stent implantation and zotarolimus-eluting stent implantation for the treatment of total coronary occlusions. AB - AIMS: Sirolimus-eluting stents (SES) have been shown to be superior to Endeavor zotarolimus-eluting stents (ZES) and comparable to Resolute ZES at eight-month angiography in patients treated for total coronary occlusions (TCO). This study investigated clinical outcome at three-year follow-up. METHODS AND RESULTS: The PRISON III trial investigated the efficacy and safety of SES against ZES (Endeavor and Resolute) in two study phases. In the first phase, 51 patients were randomised to receive SES and 46 to Endeavor ZES. In the second phase, 103 and 104 patients were randomised to SES or Resolute ZES, respectively. Between one and three years there were only a few additional clinical events in all groups. As a result, the rates of target lesion revascularisation 12.2% vs. 19.6%, p=0.49, target vessel failure 14.3% vs. 19.6%, p=0.68, and definite or probable stent thrombosis 4.1% vs. 2.2% were comparable between SES and Endeavor ZES at three years. In the second study phase, the rates of target lesion revascularisation 10% vs. 5.9%, p=0.42, target vessel failure 10% vs. 7.9%, p=0.79 and definite or probable stent thrombosis 1.0% vs. 0% were similar between SES and Resolute ZES. CONCLUSIONS: The present study demonstrated a low incidence of clinical events between one- and three-year follow-up with either SES compared to Endeavor ZES or SES versus Resolute ZES in patients treated for total coronary occlusions. PMID- 25136885 TI - Initial experience and clinical evaluation of the Absorb bioresorbable vascular scaffold (BVS) in real-world practice: the AMC Single Centre Real World PCI Registry. AB - AIMS: To report procedural and midterm clinical outcomes after the use of the second-generation Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) in a real-world percutaneous coronary intervention (PCI) registry. METHODS AND RESULTS: All patients assigned to treatment with the Absorb BVS in the Academic Medical Center, Amsterdam, between August 2012 and August 2013 were included in a prospective registry. A total of 135 patients were included in the study, including 53 (39%) acute coronary syndrome (ACS) patients (13% ST-segment elevation myocardial infarction [STEMI]). In total 159 lesions were treated, including 102 (62%) with a type B2 or C classification. Pre- and post-procedural quantitative coronary angiography (QCA) analyses showed an acute gain of 1.37+/ 0.53 mm. An angiographic success rate was achieved in 152 (96%) of the lesions. Six-month follow-up was available in 97% of the patients. Six-month cumulative target vessel failure (composite of all-cause mortality, any myocardial infarction [MI] and target vessel revascularisation [TVR]) rate was 8.5%, including a 3.0% MI, 3.0% definite scaffold thrombosis, 6.3% target lesion revascularisation, and an 8.5% TVR rate. CONCLUSIONS: The use of the Absorb BVS in a cohort reflecting daily clinical practice is feasible and associated with good procedural safety and angiographic success rate. In addition, six-month follow-up is associated with acceptable clinical outcomes. PMID- 25136886 TI - Severe infective endocarditis after MitraClip implantation treated by cardiac surgery. AB - AIMS: To report the first described case of a mitral valve infective endocarditis (IE) post MitraClip(r). METHODS AND RESULTS: An 88-year-old patient at high surgical risk (log. EuroSCORE 30.4%) underwent a MitraClip procedure for severe eccentric organic mitral regurgitation (MR) due to prolapse with a flail leaflet of the P2 segment (flail gap 6 mm). After one month, the patient was readmitted to our department for fever and recurrence of shortness of breath. An echocardiogram demonstrated severe MR recurrence due to ulceration in the region of the posterior leaflet despite good insertion of both clips, and a large vegetation of 1513 mm within the clip region. Blood cultures were positive for staphylococcus aureus. The patient was treated by cardiac surgery with mitral valve replacement due to IE despite a very high logistic EuroSCORE of 56.8%. Histological and bacteriological analysis of the clip devices confirmed active IE. After cardiac surgery, transthoracic echocardiography showed no mitral regurgitation and a mean gradient across the mitral valve bioprosthesis of about 5 mmHg. The patient was discharged to a rehabilitation department 15 days after cardiac surgery. CONCLUSIONS: Surgical treatment as bail-out therapy for MR recurrence secondary to IE after MitraClip can be successfully carried out despite a high surgical risk. PMID- 25136887 TI - Single bolus intravenous regadenoson injection versus central venous infusion of adenosine for maximum coronary hyperaemia in fractional flow reserve measurement. AB - AIMS: The aim of this study was to compare the hyperaemic effect of a single bolus regadenoson injection to a central venous adenosine infusion for inducing hyperaemia in the measurement of fractional flow reserve (FFR). METHODS AND RESULTS: One hundred patients scheduled for FFR measurement were enrolled. FFR was first measured by IV adenosine (140 ug/kg/min), thereafter by IV bolus regadenoson injection (400 ug), followed by another measurement by IV adenosine and bolus injection of regadenoson. The regadenoson injections were randomised to central or peripheral intravenous. Hyperaemic response and duration of steady state maximum hyperaemia were studied, central versus peripheral venous regadenoson injections were compared, and safety and reproducibility of repeated injections were investigated. Mean age was 66+/-8 years, 75% of the patients were male. The target stenosis was located in the LM, LAD, LCX, and RCA in 7%, 54%, 20% and 19%, respectively. There was no difference in FFR measured by adenosine or by regadenoson (DeltaFFR=0.00+/-0.01, r=0.994, p<0.001). Duration of maximum hyperaemia after regadenoson was variable (10-600 s). No serious side effects of either drug were observed. CONCLUSIONS: Maximum coronary hyperaemia can be achieved easily, rapidly, and safely by one single intravenous bolus of regadenoson administered either centrally or peripherally. Repeated regadenoson injections are safe. The hyperaemic plateau is variable. Clinical Trial Registration: http://clinicaltrials.gov/ct2/ show/study/NCT01809743?term=NCT01809743&rank=1 (ClinicalTrials.gov Identifier: NCT01809743). PMID- 25136888 TI - Safety of second-generation drug-eluting stents three years after randomised use in the TWENTE trial. AB - AIMS: To assess three-year clinical outcome following randomised use of the second-generation Resolute zotarolimus-eluting stent (ZES) and the XIENCE V everolimus-eluting stent (EES). For Resolute ZES and randomised use, outcome data >=3 years are relatively scarce. METHODS AND RESULTS: The TWENTE trial examined 1,391 patients with stable angina or non-ST-elevation acute coronary syndromes, of whom 21.6% were diabetics, 70.1% had complex B2 or C lesions and 77.4% had "off-label" indications for DES use. Three-year follow-up data were obtained in 1,381 patients (99.3%; 10 withdrawals). Adverse clinical events were independently adjudicated. The primary endpoint target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction and clinically indicated target vessel revascularisation, was 12.1% for Resolute ZES and 13.4% for XIENCE V EES (p=0.50). Cardiac death rates were 1.9% vs. 3.5% (p=0.06); the other individual components of TVF also showed no significant between-group differences. The rates of definite-or-probable stent thrombosis (1.4% vs. 1.6%, p=0.82) and very late stent thrombosis (0.6% vs. 0.4%, p=1.0) did not differ between the groups. CONCLUSIONS: Three-year follow-up data of patients included in the randomised TWENTE trial demonstrated similar and sustained safety and efficacy of Resolute ZES and XIENCE V EES. PMID- 25136889 TI - Investigation of manic and euthymic episodes identifies state- and trait-specific gene expression and STAB1 as a new candidate gene for bipolar disorder. AB - Bipolar disorder (BD) is a highly heritable psychiatric disease characterized by recurrent episodes of mania and depression. To identify new BD genes and pathways, the present study employed a three-step approach. First, gene expression profiles of BD patients were assessed during both a manic and an euthymic phase. These profiles were compared intra-individually and with the gene expression profiles of controls. Second, those differentially expressed genes that were considered potential trait markers of BD were validated using data from the Psychiatric Genomics Consortiums' genome-wide association study (GWAS) of BD. Third, the implicated molecular mechanisms were investigated using pathway analytical methods. In the present patients, this novel approach identified: (i) sets of differentially expressed genes specific to mania and euthymia; and (ii) a set of differentially expressed genes that were common to both mood states. In the GWAS data integration analysis, one gene (STAB1) remained significant (P=1.9 * 10(-4)) after adjustment for multiple testing. STAB1 is located in close proximity to PBMR1 and the NEK4-ITIH1-ITIH3-ITIH4 region, which are the top findings from GWAS meta-analyses of mood disorder, and a combined BD and schizophrenia data set. Pathway analyses in the mania versus control comparison revealed three distinct clusters of pathways tagging molecular mechanisms implicated in BD, for example, energy metabolism, inflammation and the ubiquitin proteasome system. The present findings suggest that STAB1 is a new and highly promising candidate gene in this region. The combining of gene expression and GWAS data may provide valuable insights into the biological mechanisms of BD. PMID- 25136893 TI - Viscoelasticity and interface bending properties of lecithin reverse wormlike micelles studied by diffusive wave spectroscopy in hydrophobic environment. AB - Upon the addition of minute quantities of water into a phosphatidylcholine (PC) solution in certain organic solvents, PC micelles elongate into giant reverse wormlike micelles that entangle and form highly viscous microemulsions, called lecithin organogels. We investigated the microrheological properties of concentrated PC-cyclohexane reverse wormlike micellar systems by diffusive wave spectroscopy (DWS) in apolar medium, combined with bulk shear rheology. We applied DWS to our oil-continuous system by using hydrophobic poly(hydroxystearic acid)-grafted PMMA particles as monodisperse tracer particles. Relevant parameters such as the micellar scission energy and persistence length were extracted from the microrheology data and interpreted according to the sphere-to rod-to-sphere structural transition. On the basis of these quantities, we calculated the bending and saddle-splay moduli of the PC-covered water cyclohexane interface. This approach represents a new method for the quantitative estimation of these fundamental parameters, which are thought to underpin the self-assembly of surfactants. PMID- 25136892 TI - Lithospermum erythrorhizon extract protects keratinocytes and fibroblasts against oxidative stress. AB - Oxidative stress damages dermal and epidermal cells and degrades extracellular matrix proteins, such as collagen, ultimately leading to skin aging. The present study evaluated the potential protective effect of the aqueous methanolic extract obtained from Lithospermum erythrorhizon (LE) against oxidative stress, induced by H2O2 and ultraviolet (UV) irradiation, on human keratinocyte (HaCaT) and human dermal fibroblast-neonatal (HDF-n) cells. Exposure of cells to H2O2 or UVB irradiation markedly increased oxidative stress and reduced cell viability. However, pretreatment of cells with the LE extract not only increased cell viability (up to 84.5%), but also significantly decreased oxidative stress. Further, the LE extract downregulated the expression of matrix metalloproteinase 1, an endopeptidase that degrades extracellular matrix collagen. In contrast, treatment with the LE extract did not affect the expression of procollagen type 1 in HDF-n cells exposed to UVA irradiation. Thirteen phenolic compounds, including derivatives of shikonin and caffeic acid, were identified by ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry. These results suggest that LE-derived extracts may protect oxidative-stress-induced skin aging by inhibiting degradation of skin collagen, and that this protection may derive at least in part from the antioxidant phenolics present in these extracts. Further studies are warranted to determine the potential utility of LE-derived extracts in both therapeutic and cosmetic applications. PMID- 25136894 TI - Chromatic induction from surrounding stimuli under perceptual suppression. AB - The appearance of colors can be affected by their spatiotemporal context. The shift in color appearance according to the surrounding colors is called color induction or chromatic induction; in particular, the shift in opponent color of the surround is called chromatic contrast. To investigate whether chromatic induction occurs even when the chromatic surround is imperceptible, we measured chromatic induction during interocular suppression. A multicolor or uniform color field was presented as the surround stimulus, and a colored continuous flash suppression (CFS) stimulus was presented to the dominant eye of each subject. The subjects were asked to report the appearance of the test field only when the stationary surround stimulus is invisible by interocular suppression with CFS. The resulting shifts in color appearance due to chromatic induction were significant even under the conditions of interocular suppression for all surround stimuli. The magnitude of chromatic induction differed with the surround conditions, and this difference was preserved regardless of the viewing conditions. The chromatic induction effect was reduced by CFS, in proportion to the magnitude of chromatic induction under natural (i.e., no-CFS) viewing conditions. According to an analysis with linear model fitting, we revealed the presence of at least two kinds of subprocesses for chromatic induction that reside at higher and lower levels than the site of interocular suppression. One mechanism yields different degrees of chromatic induction based on the complexity of the surround, which is unaffected by interocular suppression, while the other mechanism changes its output with interocular suppression acting as a gain control. Our results imply that the total chromatic induction effect is achieved via a linear summation of outputs from mechanisms that reside at different levels of visual processing. PMID- 25136890 TI - Dysfunctional dopaminergic neurotransmission in asocial BTBR mice. AB - Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits and stereotyped behaviours. Recent psychosocial and neuroimaging studies have highlighted reward-processing deficits and reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological and molecular determinants of these deficits remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about the origin and neurophysiological underpinnings of clinically relevant traits. Here we used functional magnetic resonance imaging (fMRI), behavioural and molecular readouts to probe dopamine neurotransmission responsivity in BTBR T(+) Itpr3(tf)/J mice (BTBR), an inbred mouse line widely used to model ASD-like symptoms owing to its robust social and communication deficits, and high level of repetitive stereotyped behaviours. C57BL/6J (B6) mice were used as normosocial reference comparators. DA reuptake inhibition with GBR 12909 produced significant striatal DA release in both strains, but failed to elicit fMRI activation in widespread forebrain areas of BTBR mice, including mesolimbic reward and striatal terminals. In addition, BTBR mice exhibited no appreciable motor responses to GBR 12909. DA D1 receptor-dependent behavioural and signalling responses were found to be unaltered in BTBR mice, whereas dramatic reductions in pre- and postsynaptic DA D2 and adenosine A2A receptor function was observed in these animals. Overall these results document profoundly compromised DA D2-mediated neurotransmission in BTBR mice, a finding that is likely to have a role in the distinctive social and behavioural deficits exhibited by these mice. Our results call for a deeper investigation of the role of dopaminergic dysfunction in mouse lines exhibiting ASD-like phenotypes, and possibly in ASD patient populations. PMID- 25136895 TI - The rise of China in the International Trade Network: a community core detection approach. AB - Theory of complex networks proved successful in the description of a variety of complex systems ranging from biology to computer science and to economics and finance. Here we use network models to describe the evolution of a particular economic system, namely the International Trade Network (ITN). Previous studies often assume that globalization and regionalization in international trade are contradictory to each other. We re-examine the relationship between globalization and regionalization by viewing the international trade system as an interdependent complex network. We use the modularity optimization method to detect communities and community cores in the ITN during the years 1995-2011. We find rich dynamics over time both inter- and intra-communities. In particular, the Asia-Oceania community disappeared and reemerged over time along with a switch in leadership from Japan to China. We provide a multilevel description of the evolution of the network where the global dynamics (i.e., communities disappear or reemerge) and the regional dynamics (i.e., community core changes between community members) are related. Moreover, simulation results show that the global dynamics can be generated by a simple dynamic-edge-weight mechanism. PMID- 25136896 TI - Is non-high-density lipoprotein cholesterol a marker and therapeutic target for dyslipidemia in metabolic syndrome? PMID- 25136897 TI - Real-world evidence in pain research: a review of data sources. AB - Outcomes research studies use clinical and administrative data generated in the course of patient care or from patient surveys to examine the effectiveness of treatments. Health care providers need to understand the limitations and strengths of the real-world data sources used in outcomes studies to meaningfully use the results. This paper describes five types of databases commonly used in the United States for outcomes research studies, discusses their strengths and limitations, and provides examples of each within the context of pain treatment. The databases specifically discussed are generated from (1) electronic medical records, which are created from patient-provider interactions; (2) administrative claims, which are generated from providers' and patients' transactions with payers; (3) integrated health systems, which are generated by systems that provide both clinical care and insurance benefits and typically represent a combination of electronic medical record and claims data; (4) national surveys, which provide patient-reported responses about their health and behaviors; and (5) patient registries, which are developed to track patients with a given disease or exposure over time for specified purposes, such as population management, safety monitoring, or research. PMID- 25136898 TI - An examination of global and regional opioid consumption trends 1980-2011. AB - Despite expert recognition that strong opioid analgesics are the cornerstone of treatment for moderate to severe pain, most of the world's population lacks adequate availability of opioids. Moreover, great disparities in availability of opioids continue to exist between higher- and lower-to-middle-income countries. This study examined more than 30 years of consumption data reported to the International Narcotics Control Board, from 1980 to 2011, for five opioids that are indicated for the treatment of moderate to severe pain: fentanyl, hydromorphone, morphine, oxycodone, and pethidine. As such, this study offers a regional and global perspective on opioid consumption, providing an indication of preparedness for treating moderate to severe pain. Countries are categorized according to the World Health Organization's six geographical regions. Morphine equivalence (ME) statistics were calculated for each study drug, allowing for equianalgesic comparisons between consumption of the study opioids and well as the ability to aggregate all study opioids (Total ME). The ME statistic is adjusted for country population, which allows for uniform global-, regional-, and country-level equianalgesic comparisons of consumption of morphine with other opioids. Although overall trend lines revealed general increases by region, profound inequities in opioid consumption continue to abound globally. PMID- 25136899 TI - TRPS1 Haploinsufficiency Results in Increased STAT3 and SOX9 mRNA Expression in Hair Follicles in Trichorhinophalangeal Syndrome. PMID- 25136900 TI - Effect of cleansing methods on saliva-contaminated zirconia--an evaluation of resin bond durability. AB - The aims of this study were to investigate 1) the influence of cleansing methods after saliva contamination and 2) aging conditions (thermocycling and water storage) on zirconia shear bond strength (SBS) with a resin cement. One hundred and eighty zirconia specimens were sandblasted with 50 MUm aluminum oxide particles, immersed in saliva for one minute (with the exception of the control group, [C]), and divided into groups according to the cleansing method, as follows: water rinse (W); 37% phosphoric acid gel (PA); cleaning paste (ie, Ivoclean(r)) containing mainly zirconium oxide (IC); and 70% isopropanol (AL). Scanning electron microscopy was done to qualitatively evaluate the zirconia surface after each cleansing method. For the SBS test, resin cement buttons were bonded to the specimens using a dedicated jig. SBS was evaluated according to standard protocols after 24 hours, 5000 thermal cycles (TC), or 150 days of water storage. Statistical analysis was performed using two-way analysis of variance and Tukey test (p<0.05). Data showed a significant effect for the 150 days of water storage, TC, and 24 hours of water storage (150 days < TC < 24 hours). Group comparisons showed that PA < AL and W < IC and C. SBS ranged from 10.4 to 21.9 MPa (24 hours), from 6.4 to 14.8 MPa (TC), and from 2.9 to 7.0 MPa (150 days). Failure analysis revealed a greater percentage of mixed failures for the majority of the specimens and a smaller percentage of adhesive failures at the ceramic-resin cement interface. Our findings suggest that Ivoclean(r) was able to maintain adequate SBS values after TC and 150 days of storage, comparable to the uncontaminated zirconia. PMID- 25136901 TI - Transdentinal cell photobiomodulation using different wavelengths. AB - OBJECTIVE: The aim of this study was to investigate the effects of transdentinal irradiation with different light-emitting diode (LED) parameters on odontoblast like cells (MDPC-23). METHODS AND MATERIALS: Human dentin discs (0.2 mm thick) were obtained, and cells were seeded on their pulp surfaces with complete culture medium (Dulbecco modified Eagle medium). Discs were irradiated from the occlusal surfaces with LED at different wavelengths (450, 630, and 840 nm) and energy densities (0, 4, and 25 J/cm(2)). Cell viability (methyltetrazolium assay), alkaline phosphatase activity (ALP), total protein synthesis (TP), and cell morphology (scanning electron microscopy) were evaluated. Gene expression of collagen type I (Col-I) was analyzed by quantitative polymerase chain reaction (PCR). Data were analyzed by the Mann-Whitney test with a 5% significance level. RESULTS: Higher cell viability (21.8%) occurred when the cells were irradiated with 630 nm LED at 25 J/cm(2). Concerning TP, no statistically significant difference was observed between irradiated and control groups. A significant increase in ALP activity was observed for all tested LED parameters, except for 450 nm at 4 J/cm(2). Quantitative PCR showed a higher expression of Col-I by the cells subjected to infrared LED irradiation at 4 J/cm(2). More attached cells were observed on dentin discs subjected to irradiation at 25 J/cm(2) than at 4 J/cm(2). CONCLUSION: The infrared LED irradiation at an energy density of 4 J/cm(2) and red LED at an energy density of 25 J/cm(2) were the most effective parameters for transdentinal photobiomodulation of cultured odontoblast-like cells. PMID- 25136902 TI - Effect of hydrogen peroxide concentration on enamel color and microhardness. AB - OBJECTIVES: The aim of this study was to investigate the effect of hydrogen peroxide gels with different concentrations (20%, 25%, 30%, and 35%) on enamel Knoop microhardness (KNH) as well as on changes in dental color (C). METHODS: Cylindrical specimens of enamel/dentin (3-mm diameter and 2-mm thickness) were obtained from bovine incisors and randomly divided into six groups (n=20), according to the concentration of the whitening gel (20%, 25%, 30%, 35%, control, thickener). After polishing, initial values of KNH0 and color measurement, assessed by spectrophotometry using the CIE L*a*b* system, were taken from the enamel surface. The gels were applied on the enamel surface for 30 minutes, and immediate values of KNHi were taken. After seven days of being stored in artificial saliva, new measures of KNH7 and color (L7* a7* b7*, for calculating DeltaE, DeltaL, and Deltab) were made. Data were submitted to statistical analysis of variance, followed by Tukey test (p<0.05). RESULTS: Differences in gel concentration and time did not influence the microhardness (p=0.54 and p=0.29, respectively). In relation to color changes, DeltaE data showed that the 35% gel presented a higher color alteration than the 20% gel did (p=0.006). CONCLUSION: Bleaching with 35% hydrogen peroxide gel was more effective than with the 20% gel, without promoting significant adverse effects on enamel surface microhardness. PMID- 25136903 TI - Influence of pH on the effectiveness of hydrogen peroxide whitening. AB - OBJECTIVE: To evaluate the influence of pH on the bleaching effect of hydrogen peroxide on chromogen agents. METHOD: Hydrogen peroxide 50% was mixed with red wine or with an alcoholic solution of tobacco in glass cuvettes, resulting in final peroxide concentrations of 16.97% and 21.12%, respectively. The pH of this mixture was measured and adjusted with 3.3 M HCl solution or 2.5 M NaOH solution to obtain the final pH values of 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, and 9.0. After mixing, the color of these solutions was evaluated in a reflectance spectrophotometer; readings were repeated after 10 minutes for the wine solution and 20 minutes for the tobacco solution. Ten samples were prepared for each solution at each pH. Color changes (Delta E) were calculated. The data were statistically analyzed using analysis of variance one-way and Tukey tests, with a significance level of 5%. RESULTS: There were significant differences among the different pH values for the wine and tobacco solutions (p=0.0001). The Tukey test showed that for both solutions, pH 9.0 resulted in a significantly greater bleaching effect than the other values tested. CONCLUSION: The efficacy of hydrogen peroxide bleaching is directly proportional to the increase in its pH. PMID- 25136904 TI - Polymerization shrinkage and depth of cure of bulk-fill resin composites and highly filled flowable resin. AB - The aim of this study was to evaluate the polymerization behavior and depth of cure (DOC) of recently introduced resin composites for posterior use: highly filled flowable composite and composites for bulk fill. A highly filled flowable (G-aenial Universal Flo [GUF]), two bulk-fill flowables (Surefil SDR Flow [SDR] and Venus Bulk fill [VBF]), and a bulk-fill nonflowable composite (Tetric N-Ceram Bulk fill [TBF]) were compared with two conventional composites (Tetric Flow [TF], Filtek Supreme Ultra [FS]). Linear polymerization shrinkage and polymerization shrinkage stress were each measured with custom-made devices. To evaluate DOC, the composite specimen was prepared using a mold with a hole of 4 mm depth and 4 mm internal diameter. The hole was bulk filled with each of the six composites and light cured for 20 seconds, followed by 24 hours of water storage. The surface hardness was measured on the top and the bottom using a Vickers microhardness (HV) indenter. The linear polymerization shrinkage of the composite specimens after photo-initiation decreased in the following order: TF and GUF > VBF > SDR > FS and TBF (p<0.05). The polymerization shrinkage stress of the six composite groups decreased in the following order: GUF > TF and VBF > SDR > FS and TBF (p<0.05). The mean bottom surface HV of SDR and VBF exceeded 80% of the top surface HV (HV-80%). However, the bottom of GUF and TBF failed to reach HV-80%. A highly filled flowable (GUF) revealed limitations in polymerization shrinkage and DOC. Bulk-fill flowables (SDR and VBF) were properly cured in 4-mm bulk, but they shrank more than the conventional nonflowable composite. A bulk fill nonflowable (TBF) showed comparable shrinkage to the conventional nonflowable composite, but it was not sufficiently cured in the 4-mm bulk. PMID- 25136905 TI - Color masking of developmental enamel defects: a case series. AB - Developmental defects involving color alteration of enamel frequently compromise the esthetic appearance of the tooth. The resin infiltration technique represents an alternative treatment for color masking of these lesions and uniformization of tooth color. This technique is considered relatively simple and microinvasive, since only a minimal portion of enamel is removed. This article illustrates the color-masking effect with resin infiltration of fluorosis and traumatic hypomineralization lesions with a case series. The final esthetic outcomes demonstrated the ability of the resin infiltrant to mask the color of white developmental defect lesions, resulting in satisfactory clinical esthetic improvements. However, in more severe cases, the color-masking effect was not complete. PMID- 25136906 TI - Efficiency of dual-cured resin cement polymerization induced by high-intensity LED curing units through ceramic material. AB - OBJECTIVE: This study aimed to evaluate the ability of high-intensity light emitting diode (LED) and other curing units to cure dual-cured resin cement through ceramic material. METHODS: A halogen curing unit (Jetlite 3000, Morita), a second-generation LED curing unit (Demi, Kerr), and two high-intensity LED curing units (PenCure 2000, Morita; Valo, Ultradent) were tested. Feldspathic ceramic plates (VITABLOCS Mark II, A3; Vita Zahnfabrik) with thicknesses of 1.0, 2.0, and 3.0 mm were prepared. Dual-cured resin cement samples (Clearfil Esthetic Cement, Kuraray Noritake Dental) were irradiated directly or through one of the ceramic plates for different periods (5, 10, 15, or 20 seconds for the high intensity LED units and 20, 40, 60, or 80 seconds for the others). The Knoop hardness test was used to determine the level of photopolymerization that had been induced in the resin cement. Data were analyzed by one-way analysis of variance and Dunnett's post-hoc test to identify test-control (maximum irradiation without a ceramic plate) differences for each curing unit (p<0.05). RESULTS: For all curing units, the curing conditions had a statistically significant effect on the Knoop hardness numbers (KHNs) of the irradiated cement samples (p<0.001). In general, the KHN decreased with increasing plate thickness and increased as the irradiation period was extended. Jetlite 3000 achieved control-level KHN values only when the plate thickness was 1.0 mm. At a plate thickness >=2.0 mm, the LED units (except for PenCure 2000 at 3.0 mm) were able to achieve control-level KHN values when the irradiation time was extended. At a plate thickness of 3.0 mm, irradiation for 20 seconds with the Valo or for 80 seconds with the Demi were the only methods that produced KHN values equivalent to those produced by direct irradiation. CONCLUSION: Regardless of the type of curing unit used, indirect irradiation of dual-cured resin cement through a ceramic plate resulted in decreased KHN values compared with direct irradiation. When the irradiation period was extended, only the LED units were able to achieve similar KHN values to those observed under direct irradiation in the presence of plates >=2.0-mm thick. High-intensity LED units require a shorter irradiation period than halogen and second-generation LED curing units to obtain KHN values similar to those observed during direct irradiation. PMID- 25136907 TI - A case report of gingival enlargement associated with invasive cervical resorption. AB - Invasive cervical resorption (ICR) is a rare external dental resorption with unknown etiology; it progresses asymptomatically in the cervical area of the permanent teeth. Lesions are mostly misdiagnosed as internal resorption or caries, which leads to erroneous treatments. This case report presents the clinical and radiological diagnosis, as well as the results of treatment and 3 year follow-up in a 50-year-old female patient with gingival enlargement associated with ICR in tooth No. 25. Granulation tissue was removed by accessing the cervical resorption area through a flap operation. Following the endodontic treatment, the tooth was restored using composite resin and the hyperplastic lesion was excised. In conclusion, it should be kept in mind that clinical, radiological, and pathological evaluation in the differential diagnosis of localized hyperplastic lesions in the gingiva is of importance and that ICR could play a role in the etiology of these lesions. PMID- 25136909 TI - The chemistry of imperfections in N-graphene. AB - Many propositions have been already put forth for the practical use of N-graphene in various devices, such as batteries, sensors, ultracapacitors, and next generation electronics. However, the chemistry of nitrogen imperfections in this material still remains an enigma. Here we demonstrate a method to handle N impurities in graphene, which allows efficient conversion of pyridinic N to graphitic N and therefore precise tuning of the charge carrier concentration. By applying photoemission spectroscopy and density functional calculations, we show that the electron doping effect of graphitic N is strongly suppressed by pyridinic N. As the latter is converted into the graphitic configuration, the efficiency of doping rises up to half of electron charge per N atom. PMID- 25136911 TI - Cycloartane triterpenoids and their glycosides from the rhizomes of Cimicifuga foetida. AB - A phytochemical study on the rhizomes of Cimicifuga foetida resulted in the isolation of two new cycloartane triterpenoids (1 and 2), eight new cycloartane glycosides (3-10), and six known cycloartane glycoside analogues (11-16). The structures of 1-10 were determined by application of spectroscopic methods, with the absolute configuration of 1 determined by X-ray crystallography. Compounds 1 6, as three pairs of epimers at C-10 and C-24, belong to a seven-membered-ring variant of 9,10-seco-9,19-cycloartane triterpenoids, and glycosides 3-10 were found to be 3-O-beta-D-xylopyranosides. The cytotoxicity of the isolates was evaluated against five selected human tumor cell lines, and the known compounds 15 and 16 showed cytotoxicity against the hepatocellular carcinoma SMMC-7721 cell line with IC50 values of 5.5 and 6.3 MUM, respectively. PMID- 25136908 TI - A novel microRNA-132-sirtuin-1 axis underlies aberrant B-cell cytokine regulation in patients with relapsing-remitting multiple sclerosis [corrected]. AB - Clinical trial results demonstrating that B-cell depletion substantially reduces new relapses in patients with multiple sclerosis (MS) have established that B cells play a role in the pathophysiology of MS relapses. The same treatment appears not to impact antibodies directed against the central nervous system, which underscores the contribution of antibody-independent functions of B cells to disease activity. One mechanism by which B cells are now thought to contribute to MS activity is by over-activating T cells, including through aberrant expression of B cell pro-inflammatory cytokines. However, the mechanisms underlying the observed B cell cytokine dysregulation in MS remain unknown. We hypothesized that aberrant expression of particular microRNAs might be involved in the dysregulated pro-inflammatory cytokine responses of B cells of patients with MS. Through screening candidate microRNAs in activated B cells of MS patients and matched healthy subjects, we discovered that abnormally increased secretion of lymphotoxin and tumor necrosis factor alpha by MS B cells is associated with abnormally increased expression of miR-132. Over-expression of miR-132 in normal B cells significantly enhanced their production of lymphotoxin and tumor necrosis factor alpha. The over-expression of miR-132 also suppressed the miR-132 target, sirtuin-1. We confirmed that pharmacological inhibition of sirtuin-1 in normal B cells induces exaggerated lymphotoxin and tumor necrosis factor alpha production, while the abnormal production of these cytokines by MS B cells can be normalized by resveratrol, a sirtuin-1 activator. These results define a novel miR-132-sirtuin-1 axis that controls pro-inflammatory cytokine secretion by human B cells, and demonstrate that a dysregulation of this axis underlies abnormal pro-inflammatory B cell cytokine responses in patients with MS. PMID- 25136912 TI - My career path for developing gene therapy for blinding diseases: the importance of mentors, collaborators, and opportunities. PMID- 25136914 TI - Gene therapy briefs. PMID- 25136915 TI - Emerging neuronal precursors from amniotic fluid-derived down syndrome induced pluripotent stem cells. PMID- 25136917 TI - Medication overuse headache - An under-diagnosed problem in shunted idiopathic intracranial hypertension patients. AB - Purpose. Management of headache in a subgroup of shunted idiopathic intracranial hypertension (IIH) patients is a well- described and difficult task. We present our series of shunted IIH patients with medication overuse headache (MOH) and discuss the role of careful pain management in this group of patients. Materials and methods. A retrospective review of shunted IIH patients with headache, who had their shunt function assessed by monitoring their intracranial pressure and were subsequently diagnosed with MOH. Results. A total of 15 patients were identified. The mean time between the diagnosis of IIH and the diagnosis of medication overuse headache was 6 years (standard deviation 4.9, range 2-18 years). The majority of patients in this group (12/15) had undergone multiple shunt revisions. Conclusions. Medication overuse headache in shunted IIH patients can lead to the requirement of hospital admission, investigations and procedures. We suggest that opiates and non-steroidal anti-inflammatory analgesics (NSAIDs) are used for a specified duration post-operatively and reviewed regularly. We suggest that patients are counselled regarding medication overuse headache in a multidisciplinary setting. PMID- 25136913 TI - Retinal gene therapy using adeno-associated viral vectors: multiple applications for a small virus. PMID- 25136918 TI - Surface plasmon dependence on the electron density profile at metal surfaces. AB - We use an extension of the hydrodynamic model to study nonlocal effects in the collective plasmon excitations at metal surfaces and narrow gaps between metals, including the surface spill-out of conduction band electrons. In particular, we simulate metal surfaces consisting of a smooth conduction-electron density profile and an abrupt jellium edge. We focus on aluminum and gold as prototypical examples of simple and noble metals, respectively. Our calculations agree with the dispersion relations measured from planar surfaces for these materials. Systems involving small gaps display a regime of tunnelling electrons, which is partially captured by the overlap of electron densities. This extension of the hydrodynamic model to cope with inhomogeneous density profiles provides a relatively fast and accurate way of describing the optical response of metal surfaces at subnanometer distances. PMID- 25136919 TI - Have preferences of girls changed almost 3 years after the much debated start of the HPV vaccination program in The Netherlands? A discrete choice experiment. AB - OBJECTIVES: To assess how girls' preferences have changed almost 3 years after the much debated start of the human papillomavirus (HPV) vaccination program. METHODS: A discrete choice experiment (DCE) was conducted among girls aged 11-15 years who were invited, or were not yet invited, to get vaccinated. A panel latent class model was used to determine girls' preferences for vaccination based on five characteristics: degree of protection against cervical cancer; duration of protection; risk of mild side-effects; age of vaccination; and the number of required doses of the vaccine. RESULTS: The response rate was 85% (500/592). Most girls preferred vaccination at age 14 years (instead of at age 9 years) and a 2 dose scheme (instead of the current 3-dose scheme). Girls were willing to trade off 7% (CI: 3.2% to 10.8%) of the degree of protection to have 10% less risk of mild side-effects, and 4% (CI: 1.2% to 5.9%) to receive 2 doses instead of 3 doses. Latent class analyses showed that there was preference heterogeneity among girls, i.e., higher educated girls and HPV vaccinated girls had a higher probability to opt for HPV vaccination at a higher age than lower educated girls or non-vaccinated girls. CONCLUSIONS: Three years after the start of HPV vaccination program the risk of mild side-effects and age at vaccination seem to have become less important. For the Dutch national immunization program, we recommend not to lower the current target age of 12 years. A 2-dose scheme may result in a higher uptake and we recommend that if this scheme is introduced, it needs to receive adequate publicity. PMID- 25136920 TI - Analysis of lymph node metastasis correlation with prognosis in patients with T2 gastric cancer. AB - PURPOSE: To investigate the correlated factors for lymph node metastasis and prognosis for patients with T2 gastric cancer. METHODS: A total of 442 patients with T2 gastric cancer who underwent gastrectomy from January 1996 to December 2009 were evaluated. The clinicopathological parameters were analyzed for lymph node metastasis and prognosis, including gender, age, tumor size, tumor location, histological type, depth of invasion, vascular tumor emboli, nervous invasion, resection type, and pathological stage. RESULTS: The rate of lymph node metastasis was 45.9%. Univariate analysis showed that depth of invasion, tumor size, and vascular tumor emboli were associated with lymph node metastasis. Logistic regression demonstrated that depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. The 5-year survival rate was 64.0%. Multivariate analysis showed that tumor size, tumor location, resection type, and pathological stage were independent prognostic factors. Based on tumor size, there were significant differences of 5 year survival between small size tumor (<6 cm) and large size tumor (>= 6 cm) according to stage IIA (P = 0.006). Based on tumor location, there were significant differences of 5-year survival among different tumor location according to stage IB. Based on resection type, there were significant differences of overall 5-year survival between curative surgery and palliative surgery according to stage IIB (P = 0.015) and IIIA (P = 0.001). CONCLUSION: Depth of invasion, tumor size, and vascular tumor emboli were independently predictive factors for lymph node metastasis. Tumor size, tumor location, resection type, and pathological stage were independent prognostic factors. PMID- 25136923 TI - New technique of immediate nipple reconstruction during immediate autologous DIEP or MS-TRAM breast reconstruction. AB - BACKGROUND: Reconstruction of the nipple-areola complex is the final step in surgical restoration of the breast. Usually considered a secondary complement to breast reconstruction, nipple-areola creation is ordinarily done after an interval of several months using different techniques involving local flaps or composite graft from the opposite nipple. METHODS: Because the position of the nipple-areola complex is well defined from the outset in skin-sparing mastectomy, the authors propose a new technique of immediate nipple reconstruction using the skin envelope after skin-sparing mastectomy. A modified wise pattern design of skin-sparing mastectomy with 3 local flaps is used. The dermal-fat flaps are lifted and sutured together to form the new nipple. RESULTS: Seventeen patients (average age, 47 years; range, 33-58 years) underwent immediate nipple reconstruction between March 2010 and January 2012 (11 bilateral and 6 unilateral cases). Average follow-up was 13 months (range, 2-25 months). Aesthetic results were evaluated retrospectively from photographic documentation. A minimum average score of 7.2 points was achieved in all evaluated criteria using a 10-point scale. Patient satisfaction with nipple reconstruction was studied by means of a questionnaire. The shape of the nipple received an average of 9.7 points and the position of the nipple 9.9 points on the 10-point scale; 77% of patients were also very satisfied with nipple sensitivity. CONCLUSIONS: One-stage nipple reconstruction with immediate breast reconstruction using our technique of 3 local flaps on skin envelope flap is possible. This simple, reliable, and rapid technique gives stable aesthetic results over time. Reconstruction may be completed sooner and with fewer procedures. Nipple reconstruction should no longer be considered as a secondary complement to immediate breast reconstruction using deep inferior epigastric perforator or muscle-sparing transverse rectus abdominis myocutaneous flap. Our technique is suitable for patients with ptotic or hypertrophic breasts. PMID- 25136922 TI - An E2F1-HOXB9 transcriptional circuit is associated with breast cancer progression. AB - Homeobox B9 (HOXB9), a member of the homeobox gene family, is overexpressed in breast cancer and promotes tumor progression and metastasis by stimulating epithelial-to-mesenchymal transition and angiogenesis within the tumor microenvironment. HOXB9 activates the TGFbeta-ATM axis, leading to checkpoint activation and DNA repair, which engenders radioresistance in breast cancer cells. Despite detailed reports of the role of HOXB9 in breast cancer, the factors that regulate HOXB9 transcription have not been extensively examined. Here we uncover an underlying mechanism that may suggest novel targeting strategies for breast cancer treatment. To identify a transcription factor binding site (TFBS) in the HOXB9 promoter region, a dual luciferase reporter assay was conducted. Protein candidates that may directly attach to a TFBS of HOXB9 were examined by Q-PCR, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), and mutation analysis. A HOXB9 promoter region from -404 to -392 was identified as TFBS, and E2F1 was a potential binding candidate in this region. The induction of HOXB9 expression by E2F1 was observed by Q-PCR in several breast cancer cell lines overexpressing E2F1. The stimulatory effect of E2F1 on HOXB9 transcription and its ability to bind the TFBS were confirmed by luciferase, EMSA and ChIP assay. Immunohistochemical analysis of 139 breast cancer tissue samples revealed a significant correlation between E2F1 and HOXB9 expression (p<0.001). Furthermore, a CDK4/6 inhibitor suppressed E2F1 expression and also reduced expression of HOXB9 and its downstream target genes. Our in vitro analysis identified the TFBS of the HOXB9 promoter region and suggested that E2F1 is a direct regulator of HOXB9 expression; these data support the strong correlation we found between E2F1 and HOXB9 in clinical breast cancer samples. These results suggest that targeting the E2F1/HOXB9 axis may be a novel strategy for the control or prevention of cancer progression and metastasis. PMID- 25136924 TI - Nickel-based thin film on multiwalled carbon nanotubes as an efficient bifunctional electrocatalyst for water splitting. AB - Herein, we report electrodeposited nickel-based thin film (NiOx) on multiwalled carbon nanotubes (MWCNTs) as a highly efficient bifunctional catalyst for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Under reductive conditions (-1.2 V vs Ag/AgCl), the hydrogen evolution catalyst (H2 NiO(x)) was facilely deposited on MWCNTs. The resulting film demonstrates good catalytic activity for hydrogen production in a near-neutral aqueous solution at low overpotential. When switched to oxidative conditions (+1.1 V vs Ag/AgCl), the amorphous H2-NiO(x) film onto MWCNTs can be transformed into another amorphous material (O2-NiO(x)) to efficiently catalyze OER. The NiO(x)-MWCNTs catalyst was further characterized by scanning electron microscopy (SEM), energy-dispersive X ray analysis (EDX), and X-ray photoelectron spectroscopy (XPS). The results show that the content of oxygen in the O2-NiO(x)-MWCNTs film is higher than that in the H2-NiO(x)-MWCNTs film. The NiOx-MWCNTs catalyst has good catalytic stability, and the film is reversible when the potentials are switched between the reductive conditions and oxidative conditions. The Faradaic efficiencies of hydrogen and oxygen production are >95%. PMID- 25136925 TI - Metamorphosis alters contaminants and chemical tracers in insects: implications for food webs. AB - Insects are integral to most freshwater and terrestrial food webs, but due to their accumulation of environmental pollutants they are also contaminant vectors that threaten reproduction, development, and survival of consumers. Metamorphosis from larvae to adult can cause large chemical changes in insects, altering contaminant concentrations and fractionation of chemical tracers used to establish contaminant biomagnification in food webs, but no framework exists for predicting and managing these effects. We analyzed data from 39 studies of 68 analytes (stable isotopes and contaminants), and found that metamorphosis effects varied greatly. delta(15)N, widely used to estimate relative trophic position in biomagnification studies, was enriched by ~ 10/00 during metamorphosis, while delta(13)C used to estimate diet, was similar in larvae and adults. Metals and polycyclic aromatic hydrocarbons (PAHs) were predominantly lost during metamorphosis leading to ~ 2 to 125-fold higher larval concentrations and higher exposure risks for predators of larvae compared to predators of adults. In contrast, manufactured organic contaminants (such as polychlorinated biphenyls) were retained and concentrated in adults, causing up to ~ 3-fold higher adult concentrations and higher exposure risks to predators of adult insects. Both food web studies and contaminant management and mitigation strategies need to consider how metamorphosis affects the movement of materials between habitats and ecosystems, with special regard for aquatic-terrestrial linkages. PMID- 25136926 TI - Nitrite and hydroxylamine as nitrogenase substrates: mechanistic implications for the pathway of N2 reduction. AB - Investigations of reduction of nitrite (NO2(-)) to ammonia (NH3) by nitrogenase indicate a limiting stoichiometry, NO2(-) + 6e(-) + 12ATP + 7H(+) -> NH3 + 2H2O + 12ADP + 12Pi. Two intermediates freeze-trapped during NO2(-) turnover by nitrogenase variants and investigated by Q-band ENDOR/ESEEM are identical to states, denoted H and I, formed on the pathway of N2 reduction. The proposed NO2( ) reduction intermediate hydroxylamine (NH2OH) is a nitrogenase substrate for which the H and I reduction intermediates also can be trapped. Viewing N2 and NO2(-) reductions in light of their common reduction intermediates and of NO2(-) reduction by multiheme cytochrome c nitrite reductase (ccNIR) leads us to propose that NO2(-) reduction by nitrogenase begins with the generation of NO2H bound to a state in which the active-site FeMo-co (M) has accumulated two [e(-)/H(+)] (E2), stored as a (bridging) hydride and proton. Proton transfer to NO2H and H2O loss leaves M-[NO(+)]; transfer of the E2 hydride to the [NO(+)] directly to form HNO bound to FeMo-co is one of two alternative means for avoiding formation of a terminal M-[NO] thermodynamic "sink". The N2 and NO2(-) reduction pathways converge upon reduction of NH2NH2 and NH2OH bound states to form state H with [ NH2] bound to M. Final reduction converts H to I, with NH3 bound to M. The results presented here, combined with the parallels with ccNIR, support a N2 fixation mechanism in which liberation of the first NH3 occurs upon delivery of five [e(-)/H(+)] to N2, but a total of seven [e(-)/H(+)] to FeMo-co when obligate H2 evolution is considered, and not earlier in the reduction process. PMID- 25136927 TI - Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure. AB - Patients with HBV-acute-on-chronic liver failure (HBV-ACLF) have high mortality and frequently require liver transplantation; few reliable prognostic markers are available. As a class of functional lipids, sphingolipids are extensively involved in the process of HBV infection. However, their role in chronic HBV infection remains unknown. The aim of this study was to determine the serum sphingolipid profile in a population of patients with chronic HBV infection, paying special attention to exploring novel prognostic markers in HBV-ACLF. High performance liquid chromatography tandem mass spectrometry was used to examine the levels of 41 sphingolipids in 156 serum samples prospectively collected from two independent cohorts. The training and validation cohorts comprised 20 and 28 healthy controls (CTRL), 29 and 23 patients with chronic hepatitis B (CHB), and 30 and 26 patients with HBV-ACLF, respectively. Biometric analysis was used to evaluate the association between sphingolipid levels and disease stages. Multivariate analysis revealed difference of sphingolipid profiles between CHB and HBV-ACLF was more drastic than that between CTRL and CHB, which indicated that serum sphingolipid levels were more likely to associate with the progression HBV-ACLF rather than CHB. Furthermore, a 3-month mortality evaluation of HBV-ACLF patients showed that dhCer(d18 : 0/24 : 0) was significantly higher in survivors than in non-survivors (including deceased patients and those undergoing liver transplantation, p < 0.05), and showed a prognostic performance similar to that of the MELD score. The serum sphingolipid composition varies between CTRL and chronic HBV infection patients. In addition, dhCer(d18 : 0/24 : 0) may be a useful prognostic indicator for the early prediction of HBV-ACLF. PMID- 25136928 TI - Synthesis and biological evaluation of kendomycin and its analogues. AB - Ansa compounds are gifts from microbes with intriguing molecular structures and highly potent bioactivities. One of the ansa compounds, kendomycin, has an oxa metacyclophane skeleton with a quinone methide core and a fully substituted tetrahydropyran ring. Beyond a common synthetic strategy for construction of the ansa skeleton (i.e., elongation of an alkyl chain from an aromatic core followed by macrocyclization), we challenged a new method for construction of the ansa skeleton via simultaneous macrocyclization and benzannulation (using an intramolecular Dotz benzannulation). Understanding the reactivity of various Fischer-type omega-alkynyloxy chromium carbene complexes with kendomycin analogue syntheses led to achievement of the total synthesis of kendomycin. Investigations of structure-activity relationships revealed the need for an ansa skeleton for antimicrobial activity. Therefore, we envisage that this intramolecular Dotz benzannulation will enable divergent syntheses of ansa compounds which have important bioactive potential. PMID- 25136930 TI - Fibroepithelial polyp of the epiglottis. AB - PATIENT: Male, 11. FINAL DIAGNOSIS: Fibroepithelial polyp of epiglottis. SYMPTOMS: Dysphagia * sore throat. MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: -. OBJECTIVE: Rare disease. BACKGROUND: Fibroepithelial polyp, a common type of tumor in the skin and genitourinary tract, is very rare in the respiratory tract. We describe clinical, radiologic, and histological features of a fibroepithelial polyp as a rare cause of an epiglottic mass in a child. CASE REPORT: An 11-year-old female presented with a 2-month history of sore throat and dysphagia. Flexible laryngoscopy and MRI (magnetic resonance imaging) revealed a mass on the lingual surface of the epiglottis. The mass was removed using a carbon dioxide laser and was confirmed histologically as a fibroepithelial polyp. CONCLUSIONS: Fibroepithelial polyp, although uncommon, should be considered in the differential diagnosis of epiglottic mass in children. PMID- 25136929 TI - Accounting for photophysical processes and specific signal intensity changes in fluorescence-detected sedimentation velocity. AB - Fluorescence detected sedimentation velocity (FDS-SV) has emerged as a powerful technique for the study of high-affinity protein interactions, with hydrodynamic resolution exceeding that of diffusion-based techniques, and with sufficient sensitivity for binding studies at low picomolar concentrations. For the detailed quantitative analysis of the observed sedimentation boundaries, it is necessary to adjust the conventional sedimentation models to the FDS data structure. A key consideration is the change in the macromolecular fluorescence intensity during the course of the experiment, caused by slow drifts of the excitation laser power, and/or by photophysical processes. In the present work, we demonstrate that FDS-SV data have inherently a reference for the time-dependent macromolecular signal intensity, resting on a geometric link between radial boundary migration and plateau signal. We show how this new time-domain can be exploited to study molecules exhibiting photobleaching and photoactivation. This expands the application of FDS-SV to proteins tagged with photoswitchable fluorescent proteins, organic dyes, or nanoparticles, such as those recently introduced for subdiffraction microscopy and enables FDS-SV studies of their interactions and size distributions. At the same time, we find that conventional fluorophores undergo minimal photobleaching under standard illumination in the FDS. These findings support the application of a high laser power density for the detection, which we demonstrate can further increase the signal quality. PMID- 25136931 TI - Comparison of the density of proteins and peptides grafted on silane layers and polyelectrolyte multilayers. AB - Immobilized proteins or peptides are of critical importance for applications such as biosensing or cell culture. We analyze the structure of layers of a large variety of proteins and peptides, grafted on silicon substrates by different routes differing in the nature of the intermediate layer linking the biomolecules to the substrate, either a silane monolayer, or a polyelectrolyte multilayer made from synthetic or natural polymers. The structural analysis is essentially performed by X-ray reflectometry, which proves to be an efficient methodology not requiring the use of tagged biomolecules, capable of evaluating consistently the amount of grafted biomolecules per surface area with estimated precisions ranging from 10 to 20%. The study provides a quantitative basis for selecting one among a series of well-proofed and sturdy grafting methodologies and underlines the potential of XRR for assessing the amount of grafted biomacromolecules without requiring the expensive tagging of molecules. Our results also show that, for the coupling route resting on synthetic polyelectrolytes, the grafting density is significantly lower than for direct coupling over a silane layer. In contrast, when performed over a cushion based on polysaccharides, the grafting density is well above the values found for a dense layer grafted on a silane monolayer, indicating partial penetration and swelling of the polysaccharide cushion. PMID- 25136932 TI - 1,3-Halogen migration as an entry to aryl coppers from an unintuitive starting material. AB - A copper(I) catalyzed 1,3-halogen migration/borylation migrates a bromine from an sp(2) carbon to a benzylic carbon with concomitant borylation of the aryl-bromine bond. This transformation proceeds via an aryl copper intermediate which can be accessed independently and then trapped with electrophiles. As such, copper catalyzed 1,3-halogen migration provides unique and mild access to an aryl copper species that allows for rapid aromatic functionalization from an unconventional starting material. PMID- 25136933 TI - Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers. AB - OBJECTIVES: Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade extracellular matrix (ECM) proteins into small soluble fragments, which reflect hepatic remodeling processes. This study used these novel biomarkers to investigate the effect of HIV and cART on hepatic fibrosis remodeling. DESIGN: In 249 patients with HIV monoinfection and 55 healthy controls, the serum levels of MMP-degraded collagen type III (C3M), biglycan (BGM), elastin (ELM), as well as the formation marker 7S (P4NP 7S), and MMP-degraded collagen type IV (C4M) were determined using specific ELISAs. Sixty-eight patients underwent a follow-up visit 3 years later including assessment of ECM markers and fibrosis using transient elastography (Fibroscan). RESULTS: C3M, BGM, C4M and P4NP 7S were significantly elevated in HIV patients compared to controls and correlated to HIV viral loads and inversely to cART duration. C4M, P4NP 7S and ELM were lower in patients under cART therapy and in patients without HIV viremia, indicating that lowering of the HIV load by cART attenuates remodeling of ECM. The levels of C3M, C4M, P4NP 7S and ELM correlated significantly with the progression of fibrosis in these patients. CONCLUSION: Specific therapy of patients with HIV monoinfection also beneficially influences liver fibrosis. These novel markers of liver fibrosis remodeling may help to monitor the hepatic effects by HIV therapy. PMID- 25136934 TI - Functionalised nanoparticles complexed with antibiotic efficiently kill MRSA and other bacteria. AB - Antibiotic-resistant bacterial infections are a vexing global health problem and have rendered ineffective many previously-used antibiotics. Here we demonstrate that antibiotic-linkage to surface-functionalized silica nanoparticles (sNP) significantly enhances their effectiveness against Escherichia coli, and Staphylococcus aureus, and even methicillin-resistant S. aureus (MRSA) strains that are resistant to most antibiotics. The commonly-used antibiotic penicillin-G (PenG) was complexed to dye-labeled sNPs (15 nm diameter) containing carboxyl groups located as either surface-functional groups, or on polymer-chains extending from surfaces. Both sNPs configurations efficiently killed bacteria, including MRSA strains. This suggests that activities of currently-ineffective antibiotics can be restored by nanoparticle-complexation and used to avert certain forms of antibiotic-resistance. PMID- 25136935 TI - Subjective Health Complaints Among Workers in the Aftermath of an Oil Tank Explosion. AB - The aim of the study was to assess whether exposed workers had more subjective health complaints than controls 1 1/2 years after a chemical explosion involving a mixture of hydrocarbons and sulfurous compounds. A cross-sectional survey based on the Subjective Health Complaints Inventory (SHC) was conducted among 147 exposed workers and 137 controls. A significantly higher total SCH score (linear regression, p=.01) was found for the exposed workers compared with controls when adjusting for gender, age, smoking habits, and educational level. The exposed workers reported significantly more headache, hot flashes, sleep problems, tiredness, dizziness, and sadness/depression. The cause of these complaints is unknown, but health personnel should be aware that health complaints might be related to polluting episodes even when exposure levels are below occupational guideline levels. PMID- 25136936 TI - What Does a Performance Measurement System Tell Us About the National Comprehensive Cancer Control Program? AB - CONTEXT: The National Comprehensive Cancer Control Program (NCCCP) performance measurement system seeks to understand both the processes that funded programs undertake with their respective coalitions to implement the objectives of their cancer plans and the outcomes of those efforts. OBJECTIVE: To identify areas of achievement and technical assistance needs of NCCCP awardees. DESIGN: Program performance was assessed through surveys completed by program directors on performance indicators in 2009 and 2010 and queries from a Web-based management information system in 2011 and 2012. SETTING: Programs funded by the Centers for Disease Control and Prevention's NCCCP. PARTICIPANTS: Sixty-nine programs. MAIN OUTCOME MEASURE(S): The key performance measures assessed were inclusion of diverse partners and key sectors in cancer coalitions, partners' involvement in activities, receiving in-kind resources from partners, using evidence-based interventions and data for setting priorities, conducting program evaluation, using community- or organization-level strategies to address cancer control efforts, and demonstrating progress toward achieving health outcomes. RESULTS: Most programs reported having active coalitions that represent diverse organizational sectors. Nearly all programs routinely assess the burden of cancer. In-kind resources to implement activities peaked at $64 716 in the second year of a 5-year funding cycle and declined in subsequent project years. By year 3, more than 70% of programs reported having an evaluation plan. While programs reported that nearly two-thirds of their interventions were evidence-based, some programs implemented non-evidence-based interventions. A majority of programs successfully used at least 1 community- or organization-level change strategy. However, many programs did not incorporate objectives linked to health outcomes as they reported progress in implementing interventions. CONCLUSIONS: While NCCCP programs were strong at building and maintaining infrastructure, some programs may need additional technical assistance to increase the adoption of evidence based interventions, develop solid and responsive evaluation plans, and better link efforts to population-based measures that demonstrate impact toward reducing the burden of cancer. PMID- 25136937 TI - The diffusion of evidence-based decision making among local health department practitioners in the United States. AB - OBJECTIVES: Evidence-based decision making (EBDM) is the process, in local health departments (LHDs) and other settings, of translating the best available scientific evidence into practice. Local health departments are more likely to be successful if they use evidence-based strategies. However, EBDM and use of evidence-based strategies by LHDs are not widespread. Drawing on diffusion of innovations theory, we sought to understand how LHD directors and program managers perceive the relative advantage, compatibility, simplicity, and testability of EBDM. DESIGN, SETTING, AND PARTICIPANTS: Directors and managers of programs in chronic disease, environmental health, and infectious disease from LHDs nationwide completed a survey including demographic information and questions about diffusion attributes (advantage, compatibility, simplicity, and testability) related to EBDM. Bivariate inferential tests were used to compare responses between directors and managers and to examine associations between participant characteristics and diffusion attributes. RESULTS: Relative advantage and compatibility scores were high for directors and managers, whereas simplicity and testability scores were lower. Although health department directors and managers of programs in chronic disease generally had higher scores than other groups, there were few significant or large differences between directors and managers across the diffusion attributes. Larger jurisdiction population size was associated with higher relative advantage and compatibility scores for both directors and managers. CONCLUSIONS: Overall, directors and managers were in strong agreement on the relative advantage of an LHD using EBDM, with directors in stronger agreement than managers. Perceived relative advantage has been demonstrated to be the most important factor in the rate of innovation adoption, suggesting an opportunity for directors to speed EBDM adoption. However, lower average scores across all groups for simplicity and testability may be hindering EBDM adoption. Recommended strategies for increasing perceived EBDM simplicity and testability are provided. PMID- 25136938 TI - Electrospun polymer mat as a SERS platform for the immobilization and detection of bacteria from fluids. AB - This work demonstrates the development of a new class of SERS substrates that allows for the simultaneous: (i) filtration of bacteria from any solution (blood, urine, water, or milk), (ii) immobilization of bacteria on the SERS platform, and (iii) enhancing the Raman signal of bacteria. The proposed platform is based on an electrospun polymer mat covered with a 90 nm layer of gold. PMID- 25136939 TI - Harms and benefits associated with exercise therapy for CFS/ME. PMID- 25136940 TI - Elements of rehabilitative strategies associated with negative outcomes in CFS/ME: the need for further investigations. PMID- 25136941 TI - Residential immersive life skills programs for youth with disabilities: service providers' perceptions of experiential benefits and key program features. AB - PURPOSE: The objective was to determine service providers' perceptions of the experiential benefits of residential immersive life skills (RILS) programs for youth with disabilities, along with important program features. METHODS: Thirty seven service providers from three RILS programs took part in qualitative interviews. Themes were derived using a phenomenological approach. RESULTS: There were perceived benefits for youth, and also for parents and service providers. Study themes concerned the process of youth empowerment, life-changing experiences for youth and parents, and changed service provider views affecting practice. Youth changes were attributed to the residential group format and afforded opportunities, which included being away from home, navigating public transportation, directing attendant services, and sharing intense learning and social experiences with peers. Youth were seen to experience important personal changes in life skills, self-confidence, self-understandings, and self-advocacy. Perceived benefits for parents included realizations concerning their child's abilities and new hope for the future. Service providers indicated changes in their knowledge, perspectives, and approach to practice. CONCLUSIONS: The findings suggest that life skills programs should be intentionally designed to provide challenging experiential opportunities that motivate youth to engage in new life directions by providing new insights, self-realizations, and positive yet realistic views of the future. IMPLICATIONS FOR REHABILITATION: Service providers indicated the importance of challenging, real-world experiential opportunities that provide youth with disabilities with new insights, self realizations, and positive yet realistic views of the future. Important experiential opportunities for youth included being away from home, navigating public transportation, directing attendant care, and sharing intense learning and social experiences with peers. The findings provide preliminary qualitative evidence that life skills programs should be intentionally designed to provide experiential opportunities that equip youth with knowledge, skills, and confidence, and motivate them to engage in new life directions. Service providers indicated important changes to their practice as a result of their involvement in a RILS program, including adopting a more holistic and facilitative approach to practice. PMID- 25136943 TI - Surgery of primary lung cancer with oligometastatic m1b synchronous single brain metastasis: analysis of 37 cases. AB - BACKGROUND: At the time of diagnosis, lung cancer has often metastasized already. Brain metastases, however, are associated with a poor prognosis (median survival of less than 1 year). We evaluated the changes of the median survival after resection of the cerebral metastases and primary non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between January 1999 and December 2009, 37 patients (22 men, 15 women; median age: 55.64 years; age range: 38-72 years) underwent surgery for primary NSCLC after craniotomy and removal of the synchronous single brain metastasis. The overall survival was evaluated and risk factors identified. RESULTS: Mediastinal lymph node involvement was excluded with mediastinoscopy in 26 of the 37 patients. Postoperative N-stage was N0, N1, and N2 in 16 (43%), 10 (27%), and 11 (30%) patients, respectively. Histology was squamous cell carcinoma in 10 (27%), adenocarcinoma in 20 (54%), and large cell carcinoma in 7 (19%). The employed type of resection was anatomical segmentectomy in 6 and lobectomy in 31 patients. The 30-day mortality was 0% and postoperative complications occurred in 12 patients only (32%). The overall 1 and 2 years survival were 62 and 24%, respectively. None of the factors age, sex, tumor histology, primary location of the tumor, type of resection, adjuvant chemotherapy, or nodal status affected survival in the univariate analysis. CONCLUSIONS: The oncologic lung resection of NSCLC after the resection of a single brain metastasis can be implemented without an increased risk of complications or mortality. Despite the stage IV disease, the median survival appears encouraging. PMID- 25136944 TI - Cardiomegaly Is a Significant Predictor of Postoperative Atelectasis following Left Upper Superior Segmentectomy. AB - BACKGROUND: Segmentectomy is becoming more common since many lung cancers are small when found. Left upper superior segmentectomy (LUSS) is the most popular procedure for segmentectomy. Atelectasis is a common postoperative complication following segmentectomy. In this study, we sought to better understand atelectasis of the lingular segment following LUSS. MATERIALS AND METHODS: Among 265 patients who underwent segmentectomy of the lung at our institute between February 2008 and August 2012, 60 patients who underwent LUSS were investigated retrospectively. An intersegmental plane was created using a stapler in 41 and by cautery in 19. The relationships between atelectasis of the lingular segment and clinical factors were analyzed by multivariate analysis. The clinical factors examined included body mass index, preoperative cardio/thoracic dimension ratio (CTR), preoperative forced expiratory volume in 1 second (FEV1), the method used to make an intersegmental plane, the interval of thoracic drainage, and the degree of lobulation. RESULTS: Atelectasis of the lingular segment was seen in nine (15.0%) patients. Preoperative CTR predicted atelectasis of the lingular segment (p = 0.004). FEV1 was preserved in 73.8% of patients with atelectasis of the lingular segment and in 86.8% of the controls. This difference was significant (p = 0.027). Atelectasis of the middle lobe following RUL was seen in 10/238 (4.2%) within the same period. CONCLUSIONS: Preoperative CTR was related to atelectasis of the lingular segment. One of the advantages of segmentectomy is that it enables the postoperative preservation of respiratory function. However, in patients with cardiomegaly, respiratory function following LUSS may be preserved less than expected. PMID- 25136945 TI - Novel thoughts on patient-prosthesis mismatch in aortic valve replacement: the rationale for the PAR I trial. AB - The hemodynamic performance of prosthetic tissue valves is influenced by valve design and valve-specific sizing strategies. Design determines the actual geometric opening area (GOA) of the prosthetic valve and sizing strategy its actual chosen size. Currently, hemodynamic performance is assessed by determining the effective orifice area (EOA; derived from the continuity equation by relating flow velocities with the area of the left ventricular outflow tract [LVOTA]). The question whether a valve is too small (patient-prosthesis mismatch [PPM]) is currently addressed by relating EOA to body surface area (EOA index [EOAi]). However, this relation may not be appropriate because the EOAi relates flow velocity to patient-specific anatomic parameters twice (i.e., LVOTA and body surface area). This potential confounder may explain the controversies regarding PPM. However, intuitively, leaving a gradient behind after aortic valve replacement cannot be irrelevant. PPM becomes even more relevant with transcatheter valve-in-valve implantation, where a second prosthesis is taking up inner space of a valve that may have already been too small initially. Thus, a reliable method to determine the presence of PPM is needed. The Prosthesis-to Annulus Relation I (PAR I) trial is a German multicenter study assessing the relation between the prosthetic GOA and the LVOTA as a potentially new parameter for the prediction of hemodynamic outcome. The results may possibly guide future valve size selection and may allow prediction of functionally relevant PPM. Here, we will demonstrate the shortcomings of the currently applied EOAi for the assessment of hemodynamic relevance and present the rationale for the PARI trial, which recently started recruiting patients. PMID- 25136946 TI - Pediatric prenatal diagnosis of congenital heart disease. AB - PURPOSE OF REVIEW: Fetal cardiology is a rapidly evolving field. Imaging technology continues to advance as do approaches to in-utero interventions and care of the critically ill neonate, with even greater demand for improvement in prenatal diagnosis of congenital heart disease (CHD) and arrhythmias. RECENT FINDINGS: Reviewing the advances in prenatal diagnosis of CHD in such a rapidly developing field is a broad topic. Therefore, we have chosen to focus this review of recent literature on challenges in prenatal detection of CHD, challenges in prenatal counseling, advances in fetal arrhythmia diagnosis, and potential benefits to patients with CHD who are identified prenatally. SUMMARY: As methods and tools to diagnose and manage CHD and arrhythmias in utero continue to improve, future generations will hopefully see a reduction in both prenatal and neonatal morbidity and mortality. Prenatal diagnosis can and should be used to optimize location and timing of delivery and postnatal interventions. PMID- 25136948 TI - Pertussis: still a cause of death, seven decades into vaccination. AB - PURPOSE OF REVIEW: We review the resurgence of pertussis, including recent trends in epidemiology and reasons for the resurgence, as well as updated vaccination schedules and recommendations. RECENT FINDINGS: There has been a resurgence of pertussis in recent decades, in the United States and worldwide. This is a preventable cause of hospitalizations and deaths, especially among the infant population. Possible reasons for the resurgence include increased awareness via surveillance and reporting, diagnostic testing improvements, infant susceptibility coupled with exposure to infected caregivers, waning immunity despite complete vaccination, inferior long-term efficacy of acellular vaccines compared with whole-cell vaccines, circulating mutant strains of the bacterium, and parents refusing vaccination of their children. Progressively updated vaccine recommendations should be adhered to, as this is currently the only available tool to stem the public health challenge. SUMMARY: The resurgence of pertussis is a multifaceted problem, but the implementation of immunization for all age groups is of utmost importance. PMID- 25136947 TI - Progress in the diagnosis and management of pulmonary hypertension in children. AB - PURPOSE OF REVIEW: Pulmonary hypertension is a complex disease that extends beyond merely elevated pulmonary blood pressures and right ventricular dysfunction. Its multiple causes and ever-expanding diagnostic tools and therapeutic approaches make it a heterogeneous disease with widely variable clinical sequelae. There are still many unanswered questions that challenge our understanding of this disease. RECENT FINDINGS: The study of pulmonary hypertension in the pediatric patient is as robust as ever, with the creation and inclusion of pediatric-specific disease characteristics in the most recent WHO classification system, improved understanding of the pathophysiology of pulmonary hypertension in pediatric diseases such as bronchopulmonary dysplasia, and increasingly expanding diagnostic tools and management possibilities. Although the use of pulmonary hypertension therapies in children previously often relied on expert opinion and inferences from studies involving adults, pediatric targeted research is becoming more widely supported and pursued, and has even come under recent debate, which at the very least stimulates further collaboration and discussion. SUMMARY: This review will highlight the changes in the pulmonary hypertension classification system, briefly explore pulmonary hypertension in bronchopulmonary dysplasia, and provide updates on the diagnostic and management tools used by experts in the field. PMID- 25136950 TI - The polar high molecular weight fraction of the Agaricus blazei Murill extract, AndoSanTM, reduces the activity of the tumor-associated protease, legumain, in RAW 264.7 cells. AB - AndoSanTM is an extract of Agaricus blazei Murill (AbM; 82.4%), Hericium erinaceum (14.7%), and Grifola frondosa (2.9%). The main ingredient of AndoSan, AbM, is rich in different forms of beta-glucans. Since these exhibit potent antitumor activity and have immunomodulatory effects, the stimulatory effect of AndoSan on the production of different cytokines, chemokines, and leukocyte growth factors has predominantly been attributed to beta-glucans. AndoSan has been claimed to consist of 90% carbohydrate, of which 2.8% is beta-glucans, but in this study, we show that the carbohydrate content is only 2% of the dry weight, corresponding to 0.09% beta-glucan per mL of AndoSan. Fractionation of AndoSan, followed by carbohydrate analysis and HPLC analysis revealed that most of the glucose was concentrated in the polar high molecular weight fraction of AndoSan (ethanol insoluble water extract [EIWE]-A) and that this extract was able to significantly inhibit the activity of the tumor-associated protease, legumain, in RAW 264.7 cells. Legumain is synthesized as a zymogen and undergoes pH dependent autoactivation of the proform to reach an enzymatically active form. In this study, we demonstrate that both the polar and nonpolar AndoSan fractions are able to inhibit the autoactivation of prolegumain, and that the polar fractions of AndoSan are the most potent inhibitors of the active form of the enzyme. PMID- 25136951 TI - Measurement of cardiac index by transpulmonary thermodilution using an implanted central venous access port: a prospective study in patients scheduled for oncologic high-risk surgery. AB - BACKGROUND: Transpulmonary thermodilution allows the measurement of cardiac index for high risk surgical patients. Oncologic patients often have a central venous access (port-a-catheter) for chronic treatment. The validity of the measurement by a port-a-catheter of the absolute cardiac index and the detection of changes in cardiac index induced by fluid challenge are unknown. METHODS: We conducted a monocentric prospective study. 27 patients were enrolled. 250 ml colloid volume expansions for fluid challenge were performed during ovarian cytoreductive surgery. The volume expansion-induced changes in cardiac index measured by transpulmonary thermodilution by a central venous access (CIcvc) and by a port-a catheter (CIport) were recorded. RESULTS: 23 patients were analyzed with 123 pairs of measurements. Using a Bland and Altman for repeated measurements, the bias (lower and upper limits of agreement) between CIport and CIcvc was 0.14 ( 0.59 to 0.88) L/min/m2. The percentage error was 22%. The concordance between the changes in CIport and CIcvc observed during volume expansion was 92% with an r = 0.7 (with exclusion zone). No complications (included sepsis) were observed during the follow up period. CONCLUSIONS: The transpulmonary thermodilution by a port-a-catheter is reliable for absolute values estimation of cardiac index and for measurement of the variation after fluid challenge. TRIAL REGISTRATION: clinicaltrials.gov NCT02063009. PMID- 25136957 TI - Self-assembled Fe3O4/polymer hybrid microbubble with MRI/ultrasound dual-imaging enhancement. AB - An Fe3O4 nanoparticle/polymer hybrid microbubble was developed using a facile self-assembly approach. This approach involves two steps, including the initial fabrication of the iron oxide nanoparticle (IONP)/polymer hybrid microcapsules via self-assembly and a subsequent gas-filling process to yield the final microbubbles. Both in vitro and in vivo experiments demonstrated that the composite gas-filled microbubbles exhibit excellent T2-weighted magnetic resonance imaging (MRI) enhancement as well as ultrasound (US) imaging enhancement capabilities. Besides, this flexible approach allows the facile control of the microbubbles' size and thus the imaging capabilities of the microbubbles through the tuning of the molar ratio between the precursors. PMID- 25136952 TI - Selective HDAC inhibition for the disruption of latent HIV-1 infection. AB - Selective histone deacetylase (HDAC) inhibitors have emerged as a potential anti latency therapy for persistent human immunodeficiency virus type 1 (HIV-1) infection. We utilized a combination of small molecule inhibitors and short hairpin (sh)RNA-mediated gene knockdown strategies to delineate the key HDAC(s) to be targeted for selective induction of latent HIV-1 expression. Individual depletion of HDAC3 significantly induced expression from the HIV-1 promoter in the 2D10 latency cell line model. However, depletion of HDAC1 or -2 alone or in combination did not significantly induce HIV-1 expression. Co-depletion of HDAC2 and -3 resulted in a significant increase in expression from the HIV-1 promoter. Furthermore, concurrent knockdown of HDAC1, -2, and -3 resulted in a significant increase in expression from the HIV-1 promoter. Using small molecule HDAC inhibitors of differing selectivity to ablate the residual HDAC activity that remained after (sh)RNA depletion, the effect of depletion of HDAC3 was further enhanced. Enzymatic inhibition of HDAC3 with the selective small-molecule inhibitor BRD3308 activated HIV-1 transcription in the 2D10 cell line. Furthermore, ex vivo exposure to BRD3308 induced outgrowth of HIV-1 from resting CD4+ T cells isolated from antiretroviral-treated, aviremic HIV+ patients. Taken together these findings suggest that HDAC3 is an essential target to disrupt HIV 1 latency, and inhibition of HDAC2 may also contribute to the effort to purge and eradicate latent HIV-1 infection. PMID- 25136958 TI - Characterization of a cross-reactive, immunodominant and HLA-promiscuous epitope of Mycobacterium tuberculosis-specific major antigenic protein PPE68. AB - PPE68 (Rv3873), a major antignic protein encoded by Mycobacteriun tuberculosis specific genomic region of difference (RD)1, is a strong stimulator of peripheral blood mononuclear cells (PBMCs) obtained from tuberculosis patients and Mycobacterium bovis bacillus Calmette Guerin (BCG)-vaccianted healthy subjects in T helper (Th)1 cell assays, i.e. antigen-induced proliferation and interferon gamma (IFN-gamma) secretion. To confirm the antigen-specific recognition of PPE68 by T cells in IFN-gamma assays, antigen-induced human T-cell lines were established from PBMCs of M. Bovis BCG-vaccinated and HLA-heterogeneous healthy subjects and tested with peptide pools of RD1 proteins. The results showed that PPE68 was recognized by antigen-specific T-cell lines from HLA-heteregeneous subjects. To further identify the immunodominant and HLA-promiscuous Th1-1 cell epitopes present in PPE68, 24 synthetic peptides covering the sequence of PPE68 were indivdually analyzed for HLA-DR binding prediction analysis and tested with PBMCs from M. bovis BCG-vaccinated and HLA-heterogeuous healthy subjects in IFN gamma assays. The results identified the peptide P9, i.e. aa 121 VLTATNFFGINTIPIALTEMDYFIR-145, as an immunodominant and HLA-DR promiscuous peptide of PPE68. Furthermore, by using deletion peptides, the immunodominant and HLA-DR promiscuous core sequence was mapped to aa 127-FFGINTIPIA-136. Interestingly, the core sequence is present in several PPE proteins of M. tuberculosis, and conserved in all sequenced strains/species of M. tuberculosis and M. tuberculosis complex, and several other pathogenic mycobacterial species, including M. leprae and M. avium-intracellulalae complex. These results suggest that the peptide aa 121-145 may be exploited as a peptide-based vaccine candidate against tuberculosis and other mycobacterial diseases. PMID- 25136959 TI - Inside money, procyclical leverage, and banking catastrophes. AB - We explore a model of the interaction between banks and outside investors in which the ability of banks to issue inside money (short-term liabilities believed to be convertible into currency at par) can generate a collapse in asset prices and widespread bank insolvency. The banks and investors share a common belief about the future value of certain long-term assets, but they have different objective functions; changes to this common belief result in portfolio adjustments and trade. Positive belief shocks induce banks to buy risky assets from investors, and the banks finance those purchases by issuing new short-term liabilities. Negative belief shocks induce banks to sell assets in order to reduce their chance of insolvency to a tolerably low level, and they supply more assets at lower prices, which can result in multiple market-clearing prices. A sufficiently severe negative shock causes the set of equilibrium prices to contract (in a manner given by a cusp catastrophe), causing prices to plummet discontinuously and banks to become insolvent. Successive positive and negative shocks of equal magnitude do not cancel; rather, a banking catastrophe can occur even if beliefs simply return to their initial state. Capital requirements can prevent crises by curtailing the expansion of balance sheets when beliefs become more optimistic, but they can also force larger price declines. Emergency asset price supports can be understood as attempts by a central bank to coordinate expectations on an equilibrium with solvency. PMID- 25136961 TI - A model for implementing guidelines for person-centered care in a nursing home setting. AB - BACKGROUND: Systematic evaluations of knowledge translation interventions in nursing homes to improve practice are scarce. There is also a lack of studies focusing on creating sustainable evidence-based practice in the setting of residential dementia care. METHODS: The aim of this paper is to describe a model for implementing national evidence-based guidelines for care of persons with dementia in nursing homes. The secondary aim is to outline the nursing home staff experiences during the first year of the implementation process. The intervention had a participatory action research approach. This included educational activities such as: (i) thematic seminars introducing national guidelines for dementia care, (ii) regular unit-based seminars; and (iii) later dissemination of information in reflective seminars and several days of poster-exhibitions. Areas of practice development were selected on each of the 24 units, based on unit specific needs, and a quality improvement strategy was applied and evaluated. Each unit met ten times during a period of eight months. Data for this study were extracted from the reflective seminars and poster presentations, analyzed using a qualitative content analysis. RESULTS: Findings showed that implementation of guidelines were perceived by staff as beneficial for both staff and the residents. However, barriers to identification of relevant sources of evidence and barriers to sustainable implementation were experienced. CONCLUSIONS: One of our assumptions was that dementia nursing homes can benefit from becoming knowledge driven, with care practices founded in evidence-based sources. Our findings show that to be partly true, even though most staff units found their efforts to pursue and utilize knowledge adversely impacted by time-logistics and practical workload challenges. PMID- 25136960 TI - Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2. AB - Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug. PMID- 25136962 TI - Costing of commune health station visits for provider payment reform in Vietnam. AB - Expanding effective coverage in Vietnam will require better use of available resources and placing higher priority on primary care. The way providers are currently paid does not give priority to primary care and does not reflect the costs of delivering services. This paper aims to estimate the unit costs of primary care visits at commune health stations (CHS) in selected areas in Vietnam. Seventy-six CHS from two provinces in northern Vietnam were studied. Costs were calculated from the perspective of the CHS using the top-down costing using the step-down cost accounting technique in order to estimate the full cost of delivering services. On average, the cost of one outpatient visit in mountainous, rural and urban CHSs was VND 49,521 (US$2.40), VND 41,375 (US$2.01) and VND 39,794 (US$1.93), respectively. Personnel costs accounted for the highest share of total costs followed by medicines. The share of operating costs was minimal. On average, CHSs recover 18.9% of their total cost for an outpatient visit from social insurance payments or fees that can be charged patients. The results provide valuable information for policy-makers as they revise the provider payment methods to better reflect the costs of services and give greater priority to primary care. PMID- 25136964 TI - The effect of insulin resistance on breast cancer risk in Latinas of Mexican origin. AB - BACKGROUND: Conclusive evidence has yet to emerge regarding the association between markers of hyperinsulinemia and breast cancer. We determined the effect of insulin resistance (IR) on breast cancer risk in Latinas of Mexican origin who did not have a direct family history of breast cancer and had not been previously diagnosed with prediabetes or diabetes. METHODS: This was a case-control study in which a case (n=124) was defined as a patient with a recent histopathologic diagnosis of breast cancer and a control (n=197) was defined as a participant who had recently undergone a mammography and had either a Breast Imaging, Reporting & Data System (BI-RADS)-1 or a BI-RADS-2 score. Plasma glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured. IR was determined by using the homeostasis model assessment (HOMA-IR) criterion. Odds ratios (OR) and 95% confidence intervals (CI) were determined using unconditional binary logistic regression analysis. RESULTS: IR was detected in 33.9% of cases and 41.6% of controls, based on a HOMA-IR >=3.5. Although multivariate analysis did not show any association between IR and breast cancer risk (OR 0.56, 95% CI 0.31-1.01), it showed that an HbA1c >=5.7% increased the risk of breast cancer (OR 3.41, 95% CI 1.93-6.01), regardless of menopausal status. CONCLUSIONS: The findings suggest that IR had no effect on breast cancer risk; however HbA1c increased the risk in Latinas of Mexican origin who had not been diagnosed previously with prediabetes or diabetes and had no direct family history of breast cancer. Prospective studies are required to establish the impact of IR over time. PMID- 25136963 TI - Transcriptional profiling in rat hair follicles following simulated Blast insult: a new diagnostic tool for traumatic brain injury. AB - With wide adoption of explosive-dependent weaponry during military activities, Blast-induced neurotrauma (BINT)-induced traumatic brain injury (TBI) has become a significant medical issue. Therefore, a robust and accessible biomarker system is in demand for effective and efficient TBI diagnosis. Such systems will also be beneficial to studies of TBI pathology. Here we propose the mammalian hair follicles as a potential candidate. An Advanced Blast Simulator (ABS) was developed to generate shock waves simulating traumatic conditions on brains of rat model. Microarray analysis was performed in hair follicles to identify the gene expression profiles that are associated with shock waves. Gene set enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) were used to identify cell processes and molecular signaling cascades affected by simulated bomb blasts. Enrichment analyses indicated that genes with altered expression levels were involved in central nervous system (CNS)/peripheral nervous system (PNS) responses as well as signal transduction including Ca2+, K+-transportation dependent signaling, Toll-Like Receptor (TLR) signaling and Mitogen Activated Protein Kinase (MAPK) signaling cascades. Many of the pathways identified as affected by shock waves in the hair follicles have been previously reported to be TBI responsive in other organs such as brain and blood. The results suggest that the hair follicle has some common TBI responsive molecular signatures to other tissues. Moreover, various TBI-associated diseases were identified as preferentially affected using a gene network approach, indicating that the hair follicle may be capable of reflecting comprehensive responses to TBI conditions. Accordingly, the present study demonstrates that the hair follicle is a potentially viable system for rapid and non-invasive TBI diagnosis. PMID- 25136966 TI - Development of multidrug resistant tuberculosis in Bangladesh: a case-control study on risk factors. AB - OBJECTIVE: To determine the risk factors for developing multidrug resistant tuberculosis in Bangladesh. METHODS: This case-control study was set in central, district and sub-district level hospitals of rural and urban Bangladesh. Included were 250 multidrug resistant tuberculosis (MDR-TB) patients as cases and 750 drug susceptible tuberculosis patients as controls. We recruited cases from all three government hospitals treating MDR-TB in Bangladesh during the study period. Controls were selected randomly from those local treatment units that had referred the cases. Information was collected through face-to-face interviews and record reviews. Unadjusted and multivariable logistic regression were used to analyse the data. RESULTS: Previous treatment history was shown to be the major contributing factor to MDR-TB in univariate analysis. After adjusting for other factors in multivariable analysis, age group "18-25" (OR 1.77, CI 1.07-2.93) and "26-45" (OR 1.72, CI 1.12-2.66), some level of education (OR 1.94, CI 1.32-2.85), service and business as occupation (OR 2.88, CI 1.29-6.44; OR 3.71, CI 1.59-8.66, respectively), smoking history (OR 1.58, CI 0.99-2.5), and type 2 diabetes (OR 2.56 CI 1.51-4.34) were associated with MDR-TB. Previous treatment was not included in the multivariable analysis as it was correlated with multiple predictors. CONCLUSION: Previous tuberculosis treatment was found to be the major risk factor for MDR-TB. This study also identified age 18 to 45 years, some education up to secondary level, service and business as occupation, past smoking status, and type 2 diabetes as comorbid illness as risk factors. National Tuberculosis programme should address these risk factors in MDR-TB control strategy. The integration of MDR-TB control activities with diabetes and tobacco control programmes is needed in Bangladesh. PMID- 25136965 TI - Built environment change and change in BMI and waist circumference: Multi-ethnic Study of Atherosclerosis. AB - OBJECTIVE: To examine longitudinal associations of the neighborhood built environment with objectively measured body mass index (BMI) and waist circumference (WC) in a geographically and racial/ethnically diverse group of adults. METHODS: This study used data from 5,506 adult participants in the Multi Ethnic Study of Atherosclerosis, aged 45-84 years in 2000 (baseline). BMI and WC were assessed at baseline and four follow-up visits (median follow-up 9.1 years). Time-varying built environment measures (population density, land-use, destinations, bus access, and street characteristics) were created using Geographic Information Systems. Principal components analysis was used to derive composite scores for three built environment factors. Fixed-effects models, tightly controlling for all time-invariant characteristics, estimated associations between change in the built environment, and change in BMI and WC. RESULTS: Increases in the intensity of development (higher density of walking destinations and population density, and lower percent residential) were associated with less pronounced increases or decreases over time in BMI and WC. Changes in connected retail centers (higher percent retail, higher street connectivity) and public transportation (distance to bus) were not associated with changes in BMI or WC. CONCLUSIONS: Longitudinal changes in the built environment, particularly increased density, are associated with decreases in BMI and WC. PMID- 25136967 TI - Age-stratified 5-year risks of cervical precancer among women with enrollment and newly detected HPV infection. AB - It is unclear whether a woman's age influences her risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) upon detection of HPV. A large change in risk as women age would influence vaccination and screening policies. Among 972,029 women age 30-64 undergoing screening with Pap and HPV testing (Hybrid Capture 2, Qiagen, Germantown, MD) at Kaiser Permanente Northern California (KPNC), we calculated age-specific 5-year CIN3+ risks among women with HPV infections detected at enrollment, and among women with "newly detected" HPV infections at their second screening visit. Women (57,899, 6.0%) had an enrollment HPV infection. Among the women testing HPV negative at enrollment with a second screening visit, 16,724 (3.3%) had a newly detected HPV infection at their second visit. Both enrollment and newly detected HPV rates declined with age (p < 0.001). Women with enrollment versus newly detected HPV infection had higher 5-year CIN3+ risks: 8.5% versus 3.9%, (p < 0.0001). Risks did not increase with age but declined slightly from 30-34 years to 60-64 years: 9.4% versus 7.4% (p = 0.017) for enrollment HPV and 5.1% versus 3.5% (p = 0.014) for newly detected HPV. Among women age 30-64 in an established screening program, women with newly detected HPV infections were at lower risk than women with enrollment infections, suggesting reduced benefit vaccinating women at older ages. Although the rates of HPV infection declined dramatically with age, the subsequent CIN3+ risks associated with HPV infection declined only slightly. The CIN3+ risks among older women are sufficiently elevated to warrant continued screening through age 65. PMID- 25136968 TI - Characterizing of functional human coding RNA editing from evolutionary, structural, and dynamic perspectives. AB - A-to-I RNA editing has been recently shown to be a widespread phenomenon with millions of sites spread in the human transcriptome. However, only few are known to be located in coding sequences and modify the amino acid sequence of the protein product. Here, we used high-throughput data, variant prediction tools, and protein structural information in order to find structural and functional preferences for coding RNA editing. We show that RNA editing has a unique pattern of amino acid changes characterized by enriched stop-to-tryptophan changes, positive-to-neutral and neutral-to-positive charge changes. RNA editing tends to have stronger structural effect than equivalent A-to-G SNPs but weaker effect than random A-to-G mutagenesis events. Sites edited at low level tend to be located at conserved positions with stronger predicted deleterious effect on proteins comparing to sites edited at high frequencies. Lowly edited sites tend to destabilize the protein structure and affect amino acids with larger number of intra-molecular contacts. Still, some highly edited sites are predicted also to prominently affect structure and tend to be located at critical positions of the protein matrix and are likely to be functionally important. Using our pipeline, we identify and discuss several novel putative functional coding changing editing sites in the genes COPA (I164V), GIPC1 (T62A), ZN358 (K382R), and CCNI (R75G). PMID- 25136969 TI - Molecular cloning and characterization of a SID-1-like gene in Plutella xylostella. AB - RNA interference (RNAi) signal can spread from the point where the double stranded RNA (dsRNA) was initially applied to other cells or tissues. SID-related genes in Caenorhabditis elegans help in the spreading of this signal. However, the mechanisms of systemic RNAi are still not unveiled in insects. In this study, we cloned a full-length cDNA of sid-1-like gene, Pxylsid-1, from Plutella xylostella that contains 1,047 bp opening reading frame encoding a putative protein of 348 amino acids. This transcript is very much similar to the sil-1 in Bombyx mori (68.8%). The higher expression levels of Pxylsid-1 were found at the adult and fourth-instar stages compared to the second-instar stage with 21.48- and 10.36-fold increase, respectively. Its expression levels in different tissues were confirmed with the highest expression in the hemolymph, which showed 21.09 fold increase than the midgut; however it was lower in other tissues. The result of RNAi by feeding bacterially expressed dsRNA targeting Pxylace-1, which showed that the mRNA level of Pxylace-1 decreased by 34.52 and 64.04% after 36- and 72-h treatment, respectively. However, the mRNA level of Pxylsid-1 was not significantly induced when the Pxylace-1 was downregulated. Furthermore, we found that downregulation of Pxylsid-1 did not affect the RNAi effect of Pxylace-1. Hence, the Pxylsid-1 may not be involved in absorption of dsRNA from the midgut fluid. A further study is needed to uncover the function of Pxylsid-1. PMID- 25136971 TI - Accuracy of semiquantitative dynamic contrast-enhanced MRI for differentiating type II from type I endometrial carcinoma. AB - PURPOSE: To investigate type II endometrial carcinoma characterization using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and evaluate the diagnostic accuracy of semiquantitative DCE-MRI in differentiating type II from type I tumors. MATERIALS AND METHODS: Seventy-seven patients with endometrial carcinoma were retrospectively evaluated using 3T DCE-MRI. The maximum absolute enhancement of signal intensity (SImax), maximum relative enhancement (SIrel), wash-in rate (WIR), and the SImax/SI (piriformis) ratio were analyzed. To differentiate type I from type II tumors, optimal threshold criteria were established. The Mann-Whitney U-test was used for statistical comparison and receiver operating characteristic curve analysis was used to determine optimal cutoff values. RESULTS: The SIrel (P < 0.001), WIR (P < 0.0001), and SImax/SI (piriformis) ratio (P < 0.0001), but not SImax, differed significantly between type I and type II carcinomas. Cutoff values of SIrel >=58.8, WIR >=37.0, and SImax/SI (piriformis) ratio >=1.55 had sensitivities of 93%, 93%, and 67%, specificities of 60%, 60%, and 79%, accuracies of 66%, 66%, and 67%, respectively, for predicting type II endometrial carcinoma. CONCLUSION: Endometrial carcinoma with strong (high level) enhancement on DCE-MRI is suggestive of type II endometrial carcinoma. Semiquantitative evaluation of DCE MRI may be useful for differentiating type II from type I tumors. PMID- 25136970 TI - Bistable expression of virulence genes in salmonella leads to the formation of an antibiotic-tolerant subpopulation. AB - Phenotypic heterogeneity can confer clonal groups of organisms with new functionality. A paradigmatic example is the bistable expression of virulence genes in Salmonella typhimurium, which leads to phenotypically virulent and phenotypically avirulent subpopulations. The two subpopulations have been shown to divide labor during S. typhimurium infections. Here, we show that heterogeneous virulence gene expression in this organism also promotes survival against exposure to antibiotics through a bet-hedging mechanism. Using microfluidic devices in combination with fluorescence time-lapse microscopy and quantitative image analysis, we analyzed the expression of virulence genes at the single cell level and related it to survival when exposed to antibiotics. We found that, across different types of antibiotics and under concentrations that are clinically relevant, the subpopulation of bacterial cells that express virulence genes shows increased survival after exposure to antibiotics. Intriguingly, there is an interplay between the two consequences of phenotypic heterogeneity. The bet-hedging effect that arises through heterogeneity in virulence gene expression can protect clonal populations against avirulent mutants that exploit and subvert the division of labor within these populations. We conclude that bet-hedging and the division of labor can arise through variation in a single trait and interact with each other. This reveals a new degree of functional complexity of phenotypic heterogeneity. In addition, our results suggest a general principle of how pathogens can evade antibiotics: Expression of virulence factors often entails metabolic costs and the resulting growth retardation could generally increase tolerance against antibiotics and thus compromise treatment. PMID- 25136972 TI - Metabolomic profiling of serum in the progression of Alzheimer's disease by capillary electrophoresis-mass spectrometry. AB - There is high interest in the discovery of early diagnostic biomarkers of Alzheimer's disease, for which metabolomics exhibits a great potential. In this work, a metabolomic approach based on ultrafiltration and analysis by CE-MS has been used to obtain representative fingerprints of polar metabolites from serum samples in order to distinguish between patients with Alzheimer's disease, mild cognitive impairment, and healthy controls. By the use of partial least squares discriminant analysis it was possible to classify patients according to the disease stage and then identify potential markers. Significant increase was observed with progression of disease in levels of choline, creatinine, asymmetric dimethyl-arginine, homocysteine-cysteine disulfide, phenylalanyl-phenylalanine, and different medium chain acylcarnitines. On the other hand, asparagine, methionine, histidine, carnitine, acetyl-spermidine, and C5-carnitine were reduced in these serum samples. In this way, multiple essential pathways were found implicated in the underlying pathology, such as oxidative stress or defects in energy metabolism. However, the most interesting results are related to the association of several vascular risk factors with Alzheimer's disease. PMID- 25136973 TI - Photoredox-catalyzed tandem radical cyclization of N-arylacrylamides: general methods to construct fluorinated 3,3-disubstituted 2-oxindoles using fluoroalkylsulfonyl chlorides. AB - Fluorinated radicals were generated from RfSO2Cl by photoredox catalysis under mild conditions, where Rf = n-C4F9, CF3, CF2H, CH2F, CH2CF3, and CF2CO2Me. This method provided a general way to construct fluorinated 2-oxindoles from reaction with N-arylacrylamides via a proposed tandem radical cyclization process. PMID- 25136974 TI - Facing the challenges of chronic pruritus: a report from a multi-disciplinary medical itch centre in Germany. AB - The complex nature and difficult-to-establish aetiology of chronic pruritus (CP) makes it challenging to provide medical care for patients with CP. This challenge can only be met with a multidisciplinary approach. The first multidisciplinary Itch Centre in Germany was established at the University of Munster in 2002 to meet the needs of this patient population. More than 2,500 outpatients and 400 inpatients are diagnosed and receive treatment each year. To ensure evidence based medical care, an electronic system for medical documentation and patient reported outcomes was established. Automated data transfer to a research database enables comprehensive data analysis. Our translational research has characterized peripheral and central itch mechanisms, provided novel clustering of CP patients, and identified novel target-specific therapies (e.g. neurokinin 1 receptor antagonist). The multidisciplinary approach, combined with basic, clinical and translational research, enables comprehensive medical care of patients as well as implementation of high-quality experimental and clinical studies. PMID- 25136975 TI - Shell-programmed Au nanoparticle heterodimers with customized chiroptical activity. AB - Chiral plasmonic assemblies with strong and tunable chiroptical activity are emerging materials yet challenging to fabricate. Moreover, shell-programmed chiroptical regulation is really rare. Here, the chiroptical activity of core shell (CS) nanoparticles (NPs) heterodimers (HDs) with different types and thicknesses of the shell but featuring the same gap was exploited. It was found that the type of shell guided the position of the chiral peaks, and the shell thickness tuned the intensity but also moderately affected the wavelength shift at invariable interparticle distance. Shell deposition intensified the hot-spot chirality, and evidently guided the enantiomorphous chiral configuration, resulting in a startlingly intense, asymmetric, dipolar coupling strength. The magnitude of the chiroptical activity showed an 8-10 fold enhancement with a maximum anisotropy factor (g-factor) of 1.5 * 10(-2) . Shell-driven chiroptical regulation opens new avenues to feasibly fabricate chiroptically active materials with desired chiroptical response for the development of switchable recognition units for sensitive and various target detections. PMID- 25136977 TI - A CASE OF HAEMATIDROSIS. PMID- 25136976 TI - Enzymatic degradation of (ligno)cellulose. AB - Glycoside-degrading enzymes play a dominant role in the biochemical conversion of cellulosic biomass into low-price biofuels and high-value-added chemicals. New insight into protein functions and substrate structures, the kinetics of recognition, and degradation events has resulted in a substantial improvement of our understanding of cellulose degradation. PMID- 25136978 TI - The important role of catestatin in cardiac remodeling. AB - Catestatin (CST) was first discovered as a potent non-competitive and reversible inhibitor of catecholamine secretion. Recent reports on plasma CST level in heart diseases suggested a cardioprotective role for this peptide. Given that cardiac remodeling is the dominant pathologic process in cardiac dysfunction, we propose that CST participates in the regulation of concern pathways and contributes to the inhibition of cardiac remodeling. In this minireview, the potential mechanism of cardiac remodeling involving CST will be discussed from three aspects: hypertrophy, fibrosis, and apoptosis. PMID- 25136979 TI - Concordant biogeographic patterns among multiple taxonomic groups in the Mexican freshwater biota. AB - In this paper we analyse the degree of concordance in species richness and taxonomic distinctness (diversity) patterns among different freshwater taxonomic groups in order to test three long held patterns described in Mexican freshwater biogeography: 1. The aquatic biota of Mexico includes two distinct faunas, a rich Neotropical component in the south and a south-eastern region and a less rich Nearctic component towards central and northern latitudes of the country. 2. A hotspot of species richness and diversity has been recorded in the Usumacinta, including the Yucatan Peninsula. 3. The presence of two distinct biotas in Mexico, an eastern one distributed along the Gulf of Mexico slope, and a western one associated to the Pacific versant. We use species richness and taxonomic distinctness to explore patterns of diversity and how these patterns change between zoogeographical regions. This paper points out a clear separation between Neotropical and Nearctic drainage basins but also between eastern (Gulf of Mexico) and western (Pacific) drainage basins. Present data gives additional empirical support from freshwater biota for three long held beliefs regarding distributional patterns of the Mexican biota. The neotropical basins of Mexico are generally host to a richest and more diversified fauna, that includes more families, genera and species, compared to the less rich and less diverse fauna in the nearctic basins. PMID- 25136980 TI - Unveiling the correlation between nanometer-thick molecular monolayer sensitivity and near-field enhancement and localization in coupled plasmonic oligomers. AB - Metal nanoclusters, sometimes called metamolecules or plasmonic oligomers, exhibit interesting optical properties such as Fano resonances and optical chirality. These properties promise a variety of practical applications, particularly in ultrasensitive biochemical sensing. Here we investigate experimentally the sensitivities of plasmonic pentamers and quadrumers to the adsorption of self-assembled nanometer-thick alkanethiol monolayers. The monolayer sensitivity of such oligomers is found to be significantly higher than that of single plasmonic nanoparticles and depends on the nanocluster arrangement, constituent nanoparticle shape, and the plasmon resonance wavelength. Together with full-wave numerical simulation results and the electromagnetic perturbation theory, we unveil a direct correlation between the sensitivity and the near-field intensity enhancement and spatial localization in the plasmonic "hot" spots generated in each nanocluster. Our observation is beyond conventional considerations (such as optimizing nanoparticle geometry or narrowing resonance line width) for improving the sensing performance of metal nanoclusters-based biosensors and opens the possibilities of using plasmonic nanoclusters for single-molecule detection and identification. PMID- 25136982 TI - Registration of 2D histological sections with 3D micro-CT datasets from small animal vertebrae and tibiae. AB - The aim of this study was the registration of digitized thin 2D sections of mouse vertebrae and tibiae used for histomorphometry of trabecular bone structure into 3D micro computed tomography (MUCT) datasets of the samples from which the sections were prepared. Intensity-based and segmentation-based registrations (SegRegs) of 2D sections and 3D MUCT datasets were applied. As the 2D sections were deformed during their preparation, affine registration for the vertebrae was used instead of rigid registration. Tibiae sections were additionally cut on the distal end, which subsequently undergone more deformation so that elastic registration was necessary. The Jaccard distance was used as registration quality measure. The quality of intensity-based registrations and SegRegs was practically equal, although precision errors of the elastic registration of segmentation masks in tibiae were lower, while those in vertebrae were lower for the intensity based registration. Results of SegReg significantly depended on the segmentation of the MUCT datasets. Accuracy errors were reduced from approximately 64% to 42% when applying affine instead of rigid transformations for the vertebrae and from about 43% to 24% when using B-spline instead of rigid transformations for the tibiae. Accuracy errors can also be caused by the difference in spatial resolution between the thin sections (pixel size: 7.25 MUm) and the MUCT data (voxel size: 15 MUm). In the vertebrae, average deformations amounted to a 6.7% shortening along the direction of sectioning and a 4% extension along the perpendicular direction corresponding to 0.13-0.17 mm. Maximum offsets in the mouse tibiae were 0.16 mm on average. PMID- 25136981 TI - Potentially inappropriate medication use in older patients in Swiss managed care plans: prevalence, determinants and association with hospitalization. AB - OBJECTIVES: To describe the prevalence and determinants of potentially inappropriate medication (PIM) use and association with hospitalizations in an elderly managed care population in Switzerland. METHODS: Using health care claims data of four health insurers for a sample of managed care patients 65 years of age and older to compare persons on PIM with persons not on PIM. Beers' 2012 and PRISCUS criteria were used to determine the potential inappropriateness of prescribed medications. The sample included 16'490 elderly patients on PIM and 33'178 patients not on PIM in the time period of January 1, 2008 through December 31, 2012. Prevalence estimates are standardized to the population of Switzerland. Associations between PIM and hospitalizations were examined by multivariate Cox regression analyses controlling for possible confounding variables. RESULTS: The estimated prevalence of PIM use in our managed care sample was 22.5%. Logistic regression analysis showed that number of different medications used in the previous year, total costs in the previous year and hospitalization in the previous year all significantly increased the likelihood of receiving PIM. Multiple Cox regression analysis revealed that those on cumulative levels of PIM use acted significantly as a factor related to greater hospitalization rates: the adjusted HR was 1.13 (95% CI 1.07-1.19) for 1 PIM, 1.27 (95% CI 1.19-1.35) for 2 PIM, 1.35 (95% CI 1.22-1.50) for 3 PIM, and 1.63 (95% CI 1.40-1.90) for more than 3 PIM compared to no PIM use. CONCLUSIONS: The prevalence of PIM in managed care health plans are widely found but seem to be much lower than rates of non-managed care plans. Furthermore, our study revealed a significant association with adverse outcomes in terms of hospitalizations. These findings stress the need for further development of interventions to decrease drug-related problems and manage patients with multiple chronic conditions. PMID- 25136983 TI - Influence of organic solvents on catalytic behaviors and cell morphology of whole cell biocatalysts for synthesis of 5'-arabinocytosine laurate. AB - A whole-cell based method was developed for the regioselective synthesis of arabinocytosine laurate. Among the seven kinds of bacteria strains tested in the acylation reaction, Pseudomonas fluorescens gave the highest productivity and a higher 5'-regioselectivity than 99%. Compared with pure organic solvents, the use of organic solvent mixtures greatly promoted the yield of the whole-cell catalyzed reaction, but showed little influence on the 5'-regioselectivity. Of all the tested solvent mixtures, the best reaction result was found in isopropyl ether/pyridine followed by isopentanol/pyridine. However, the whole-cells showed much lower thermostability in isopropyl ether/pyridine than in THF-pyridine. To better understand the toxic effects of the organic solvents on P. fluorescens whole-cells and growing cells were further examined. Significant influences of organic solvents on the biomass of the cells were found, which differed depending on the type of solvents used. SEM analysis visually revealed the changes in the surface morphology of whole-cells and growing cells cultured in media containing various organic solvents, in terms of surface smoothness, bulges and changed cell sizes. Results demonstrated that organic toxicity to cell structure played an important role in whole-cell mediated catalysis. PMID- 25136985 TI - Sequential inclusion of two berberine cations in cucurbit[8]uril cavity: kinetic and thermodynamic studies. AB - A combination of absorption and fluorescence spectroscopic studies with isothermal calorimetric titrations and stopped-flow measurements is a powerful way to reveal the thermodynamics and kinetics of inclusion complex formation with cucurbit[8]uril (CB8). The unique photophysical characteristics of berberine (B(+)), a pharmaceutically important natural alkaloid, were exploited to distinguish the consecutive encapsulation processes, and to examine the confinement in the CB8 cavity. The highly environment sensitive fluorescence lifetime of B(+) permitted the selective detection of various cucurbituril complexes, and indicated to what extent the embedded guest was available for interaction with water. Highly stable 1 : 1 and 2 : 1 B(+) : CB8 complexes were produced due to the release of the high energy water molecules from the CB8 interior, and the second binding step proved to be almost 3 times more exothermic. The favorable entropy change contributed appreciably to the driving force of 1 : 1 encapsulation. In contrast, the embedment of the second B(+) in CB8 led to substantial entropy diminution. The kinetics of encapsulation was followed in real time by recording the fluorescence intensity change after rapid mixing of B(+) and CB8. No evidence was found for intermediates. The rate constants of (64 +/- 9) * 10(6), and (5.0 +/- 0.5) * 10(6) M(-1) s(-1) were found for the 1 : 1 and 2 : 1 associations, whereas 3.8 +/- 0.6, and 0.6 +/- 0.1 s(-1) were obtained as the rate constants of the reverse processes at 283 K, respectively. PMID- 25136986 TI - Interface recombination current in type II heterostructure bipolar diodes. AB - Wide-gap semiconductors are often unipolar and can form type II bipolar heterostructures with large band discontinuities. We present such diodes with very high rectification larger than 1 * 10(10). The current is assumed to be entirely due to interface recombination. We derive the ideality factor for both symmetric and asymmetric diodes and find it close to 2 in agreement with experimental data from NiO/ZnO and CuI/ZnO type II diodes. The comparison with experimental results shows that the actual interface recombination rate is orders of magnitude smaller than its possible maximum value. PMID- 25136984 TI - Rhinitis, asthma and respiratory infections among adults in relation to the home environment in multi-family buildings in Sweden. AB - Risk factors for rhinitis, asthma and respiratory infections in the home environment were studied by a questionnaire survey. Totally 5775 occupants (>= 18 years old) from a stratified random sample of multi-family buildings in Sweden participated (46%). 51.0% had rhinitis in the last 3 months (current rhinitis); 11.5% doctor diagnosed asthma; 46.4% respiratory infections in the last 3 months and 11.9% antibiotic medication for respiratory infections in the last 12 months. Associations between home environment and health were analyzed by multiple logistic regression, controlling for gender, age and smoking and mutual adjustment. Buildings constructed during 1960-1975 were risk factors for day time breathlessness (OR = 1.53, 95%CI 1.03-2.29). And those constructed during 1976 1985 had more current rhinitis (OR = 1.43, 95%CI 1.12-1.84) and respiratory infections (OR = 1.46, 95%CI 1.21-1.78). Cities with higher population density had more current rhinitis (p = 0.008) and respiratory infections (p<0.001). Rented apartments had more current rhinitis (OR = 1.23, 95%CI 1.07-1.40), wheeze (OR = 1.20, 95%CI 1.02-1.41), day time breathlessness (OR = 1.31, 95%CI 1.04 1.66) and respiratory infections (OR = 1.13, 95%CI 1.01-1.26). Living in colder parts of the country was a risk factor for wheeze (p = 0.03) and night time breathlessness (p = 0.002). Building dampness was a risk factor for wheeze (OR = 1.42, 95%CI 1.08-1.86) and day time breathlessness (OR = 1.57, 95%CI 1.09-2.27). Building dampness was a risk factor for health among those below 66 years old. Odor at home was a risk factor for doctor diagnosed asthma (OR = 1.49, 95%CI 1.08 2.06) and current asthma (OR = 1.52, 95%CI 1.03-2.24). Environmental tobacco smoke (ETS) was a risk factor for current asthma (OR = 1.53, 95%CI 1.09-2.16). Window panel condensation was a risk factor for antibiotic medication for respiratory infections (OR = 1.41, 95%CI 1.10-1.82). In conclusion, rhinitis, asthma and respiratory infections were related to a number of factors in the home environment. Certain building years (1961-1985), building dampness, window panel condensation and odor in the dwelling may be risk factors. PMID- 25136987 TI - The potential impact of a 20% tax on sugar-sweetened beverages on obesity in South African adults: a mathematical model. AB - BACKGROUND/OBJECTIVES: The prevalence of obesity in South Africa has risen sharply, as has the consumption of sugar-sweetened beverages (SSBs). Research shows that consumption of SSBs leads to weight gain in both adults and children, and reducing SSBs will significantly impact the prevalence of obesity and its related diseases. We estimated the effect of a 20% tax on SSBs on the prevalence of and obesity among adults in South Africa. METHODS: A mathematical simulation model was constructed to estimate the effect of a 20% SSB tax on the prevalence of obesity. We used consumption data from the 2012 SA National Health and Nutrition Examination Survey and a previous meta-analysis of studies on own- and cross-price elasticities of SSBs to estimate the shift in daily energy consumption expected of increased prices of SSBs, and energy balance equations to estimate shifts in body mass index. The population distribution of BMI by age and sex was modelled by fitting measured data from the SA National Income Dynamics Survey 2012 to the lognormal distribution and shifting the mean values. Uncertainty was assessed with Monte Carlo simulations. RESULTS: A 20% tax is predicted to reduce energy intake by about 36 kJ per day (95% CI: 9-68 kJ). Obesity is projected to reduce by 3.8% (95% CI: 0.6%-7.1%) in men and 2.4% (95% CI: 0.4%-4.4%) in women. The number of obese adults would decrease by over 220 000 (95% CI: 24 197-411 759). CONCLUSIONS: Taxing SSBs could impact the burden of obesity in South Africa particularly in young adults, as one component of a multi faceted effort to prevent obesity. PMID- 25136989 TI - Non-injection synthesis of doped zinc oxide plasmonic nanocrystals. AB - Plasmonic metal oxide nanocrystals bridge the optoelectronic gap between semiconductors and metals. In this study, we report a facile, non-injection synthesis of ZnO nanocrystals doped with Al, Ga, or In. The reaction readily permits dopant/zinc atomic ratios of over 15%, is amenable to high precursor concentrations (0.2 M and greater), and provides high reaction yields (>90%). The resulting colloidal dispersions exhibit high transparency in the visible spectrum and a wavelength-tunable infrared absorption, which arises from a dopant-induced surface plasmon resonance. Through a detailed investigation of reaction parameters, the reaction mechanism is fully characterized and correlated to the optical properties of the synthesized nanocrystals. The distinctive optical features of these doped nanocrystals are shown to be readily harnessed within thin films that are suitable for optoelectronic applications. PMID- 25136990 TI - Milling, water uptake, and modification properties of different barley (Hordeum vulgare L.) lots in relation to grain composition and structure. AB - Milling properties, water uptake, and modification in malting were studied in 14 barley (Hordeum vulgare L.) lots from two consecutive crop years. In all barley lots studied, grains with lower beta-glucan and protein content and higher starch content produced finer flours upon milling. Grains with lower beta-glucan content also hydrated more rapidly during steeping. A detailed study of two cultivars from two crop years indicated that similar environmental conditions could induce a higher beta-glucan content and concentration of aggregated B hordein in the peripheral endosperm and a lower proportion of C hordein entrapped among aggregated hordeins deeper within the endosperm. These characteristics were associated with production of coarser flours during milling as well as with slower water uptake and lower modification. However, the data do not distinguish between the effect of beta-glucan content and that of hordein localization. Distribution of beta-glucan or total protein within the kernel was not linked to hydration or modification. PMID- 25136988 TI - High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis. AB - BACKGROUND: High interleukin (IL)-17A levels are characteristically found in the skin of systemic sclerosis (SSc) individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL 17E and IL-17F) could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis. METHODS: Biopsies were obtained from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD) undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA. RESULTS: Positive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237) and decreased frequency of IL-17F+ (p = 0.0127) and IL-17C+ cells (p = 0.0008) when compared to HD. Similarly, morphea individuals had less frequent IL 17C+ cells (p = 0.0186) in their skin but showed similar number of IL-17A+ and IL 17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109) and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration. CONCLUSIONS: The frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low) and IL-17E (high) identifies a fibrosis-specific motif. The specific IL-17C/IL 17E cytokine combination may thus play a role in the development of fibrosis. PMID- 25136991 TI - Visible light-driven pure water splitting by a nature-inspired organic semiconductor-based system. AB - For the first time, it is demonstrated that the robust organic semiconductor g C3N4 can be integrated into a nature-inspired water splitting system, analogous to PSII and PSI in natural photosynthesis. Two parallel systems have been developed for overall water splitting under visible light involving graphitic carbon nitride with two different metal oxides, BiVO4 and WO3. Consequently, both hydrogen and oxygen can be evolved in an ideal ratio of 2:1, and evolution rates in both systems have been found to be dependent on pH, redox mediator concentration, and mass ratio between the two photocatalysts, leading to a stable and reproducible H2 and O2 evolution rate at 36 and 18 MUmol h(-1) g(-1) from water over 14 h. Our findings demonstrate g-C3N4 can serve as a multifunctional robust photocatalyst, which could also be used in other systems such as PEC cells or coupled solar cell systems. PMID- 25136992 TI - Magnetic coupling and slow relaxation of magnetization in chain-based Mn(II), Co(II), and Ni(II) coordination frameworks. AB - Three isomorphous coordination polymers based on the chain with triple (MU-1,1 N3)(MU-1,3-COO)2 bridges have been synthesized from a new zwitterionic dicarboxylate ligand [L(-) = 1-(4-carboxylatobenzyl)pyridinium-4-carboxylate]. They are of formula [M(L)(N3)]n.3nH2O [M = Mn(II), Co(II), and Ni(II)]. In these compounds, the mixed-bridge chains are linked into 2D coordination networks by the N-benzylpyridinium spacers. The magnetic properties depend strongly on the nature of the metal center. The magnetic coupling through (MU-1,1-N3)(MU-1,3 COO)2 is antiferromagnetic in the Mn(II) compound but ferromagnetic in the Co(II) and Ni(II) analogues. Magnetostructural analyses indicate that the magnitude of the magnetic coupling can be correlated to the M-N-M angle of the azide bridge and the average M-O-C-O torsion angle of the carboxylate bridge. As the values of these parameters increase, the antiferromagnetic coupling for Mn(II) decreases while the ferromagnetic coupling for Co(II) increases. With strong magnetic anisotropy, the Co(II) compound behaves as a single-chain magnet showing hysteresis and Glauber-type slow dynamics probably in the infinite-chain region, with Delta(tau)/k = 86 K, Delta(xi)/k = 26 K, and Delta(A)/k = 34 K. With weaker anisotropy, the Ni(II) species shows slow relaxation of magnetization at much lower temperature. PMID- 25136993 TI - Do neuraxial techniques affect perioperative outcomes? The story of vantage points and number games. PMID- 25136994 TI - Vitamin D and your patients: don't accept wimpy. PMID- 25136995 TI - The growing burden of perioperative heart failure. PMID- 25136996 TI - Hydroxyethyl starches: a tale of two contexts: the problem of knowledge. PMID- 25136997 TI - Cognitive outcomes after infant spinal anesthesia: the other side of the coin. PMID- 25136998 TI - Goal-directed therapy: time to move on? PMID- 25136999 TI - Hypovitaminosis D in hospitalized patients: a marker of frailty or a disease requiring treatment? PMID- 25137000 TI - Positive end-expiratory pressure to increase internal jugular vein size is poorly tolerated in obese anesthetized adults. AB - BACKGROUND: Central venous cannulation is technically challenging in obese patients. We hypothesized that positive end-expiratory pressure (PEEP) increases the size of the internal jugular vein (IJV) in obese adults. METHODS: The circumference and cross-sectional area of the IJV were measured in obese patients under general anesthesia at PEEP 0, 5, and 10 cm H2O. Results are reported as means +/- SE. RESULTS: PEEP at 10 cm H2O was tolerated by 18 of 24 obese patients. Each 5 cm H2O of PEEP increased the cross-sectional area by 0.16 +/- 0.02 cm (P < 0.0001) and the circumference by 0.23 +/- 0.03 cm (P < 0.0001). CONCLUSIONS: PEEP modestly increases the size of the IJV in obese adults but was poorly tolerated because of hypotension. PMID- 25137001 TI - Neurodevelopmental assessment after anesthesia in childhood: review of the literature and recommendations. AB - Preclinical studies have established that anesthesia is toxic to the brain in neonatal animals, but scant research investigates the neurodevelopmental effects of exposure to anesthesia. In this article, we discuss the issue of outcome measurement of children after anesthesia administered between infancy and approximately 4 years of age. Recent studies are reviewed with the goal of understanding the contributions and limitations of the extant literature with respect to neurodevelopmental outcome. A review of school-based information (academic achievement and learning disability characterization), which are most frequently applied to measure cognitive outcome in cohort studies, is provided. The strengths and limitations of this literature is reviewed, followed by a discussion of how future trials investigating neurodevelopmental outcome after anesthesia might be improved by procedures designed specifically to assess the status of the central nervous system. Neuropsychological assessment is described and proposed as a way to increase the validity and sensitivity of forthcoming studies that intend to evaluate the short- and long-term effects of exposure to anesthesia during infancy and early childhood. PMID- 25137002 TI - Bernoulli Cumulative Sum (CUSUM) control charts for monitoring of anesthesiologists' performance in supervising anesthesia residents and nurse anesthetists. AB - We describe our experiences in using Bernoulli cumulative sum (CUSUM) control charts for monitoring clinician performance. The supervision provided by each anesthesiologist is evaluated daily by the Certified Registered Nurse Anesthetists (CRNAs) and/or anesthesia residents with whom they work. Each of 9 items is evaluated (1 = never, 2 = rarely, 3 = frequently, 4 = always). The score is the mean of the 9 responses. Choosing thresholds for low scores is straightforward, <2.0 for CRNAs and <3.0 for residents. Bernoulli CUSUM detection of low scores was within 50 +/- 14 (median +/- quartile deviation) days rather than 182 days without use of CUSUM. The true positive detection of anesthesiologists with incidences of low scores greater than the chosen "out-of control" rate was 14 of 14. The false-positive detection rate was 0 of 29. This CUSUM performance exceeded that of Shewhart individual control charts, for which the smallest threshold sufficiently large to detect 14 of 14 true positives had false-positive detection of 16 of 29 anesthesiologists. The Bernoulli CUSUM assumes that scores are known right away, which is untrue. However, CUSUM performance was insensitive to this assumption. The Bernoulli CUSUM assumes statistical independence of scores, which also is untrue. For example, when an evaluation of an anesthesiologist 1 day by a CRNA had a low score, there was an increased chance that another CRNA working in a different operating room on the same day would also give that same anesthesiologist a low score (P < 0.0001). This correlation among scores does affect the Bernoulli CUSUM, such that detection is more likely. This is an advantage for our continual process improvement application since it flags individuals for further evaluation by managers while maintaining confidentiality of raters. PMID- 25137004 TI - Intravenous starches: is suspension the best solution? PMID- 25137003 TI - Interleukin 10 mediated by herpes simplex virus vectors suppresses neuropathic pain induced by human immunodeficiency virus gp120 in rats. AB - BACKGROUND: Human immunodeficiency virus (HIV)-associated sensory neuropathy is a common neurological complication of HIV infection affecting up to 30% of HIV positive individuals. However, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments for HIV related neuropathic pain (NP). In this study, we tested the hypothesis that inhibition of proinflammatory factors with overexpression of interleukin (IL)-10 reduces HIV-related NP in a rat model. METHODS: NP was induced by the application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. The hindpaws of rats were inoculated with nonreplicating herpes simplex virus (HSV) vectors expressing anti-inflammatory cytokine IL-10 or control vector. Mechanical threshold was tested using von Frey filaments before and after treatments with the vectors. The mechanical threshold response was assessed over time using the area under curves. The expression of phosphorylated p38 mitogen-activated kinase, tumor necrosis factor-alpha, stromal cell-derived factor-1alpha, and C-X-C chemokine receptor type 4 in both the lumbar spinal cord and the L4/5 dorsal root ganglia (DRG), was examined at 14 and 28 days after vector inoculation using Western blots. RESULTS: We found that in the gp120-induced NP model, IL-10 overexpression mediated by the HSV vector resulted in a significant elevation of the mechanical threshold that was apparent on day 3 after vector inoculation compared with the control vector (P < 0.001). The antiallodynic effect of the single HSV vector inoculation expressing IL-10 lasted >28 days. The area under curve in the HSV vector expressing IL-10 was increased compared with that in the control vector (P < 0.0001). HSV vectors expressing IL-10 reversed the upregulation of phosphorylated p38 mitogen-activated kinase, tumor necrosis factor-alpha, stromal cell-derived factor-1alpha, and C-X-C chemokine receptor type 4 expression at 14 and/or 28 days in the DRG and/or the spinal dorsal horn. CONCLUSIONS: Our studies demonstrate that blocking the signaling of these proinflammatory molecules in the DRG and/or the spinal cord using the HSV vector expressing IL-10 is able to reduce HIV-related NP. These results provide new insights on the potential mechanisms of HIV-associated NP and a proof of concept for treating painful HIV sensory neuropathy with this type of gene therapy. PMID- 25137005 TI - Volume therapy with hydroxyethyl starches: are we throwing the anesthesia baby out with the intensive care unit bathwater? PMID- 25137006 TI - Does regional analgesia for major surgery improve outcome? Focus on epidural analgesia. PMID- 25137007 TI - Does it expire, or doesn't it? Only the manufacturer knows for sure. PMID- 25137008 TI - Plagiarism by any other name (author)? PMID- 25137009 TI - Textbook plagiarism reform. PMID- 25137010 TI - Why is there still plagiarism? PMID- 25137011 TI - In response. PMID- 25137012 TI - Improved quality of anesthesia and cancer recurrence studies. PMID- 25137013 TI - Small-molecule inhibitors of SETD8 with cellular activity. AB - SETD8/SET8/Pr-SET7/KMT5A is the sole protein lysine methyltransferase (PKMT) known to monomethylate lysine 20 of histone H4 in vivo. SETD8's methyltransferase activity has been implicated in many essential cellular processes including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. Developing SETD8 inhibitors with cellular activity is a key step toward elucidating the diverse roles of SETD8 via convenient pharmacological perturbation. From the hits of a prior high throughput screen (HTS), SPS8I1-3 (NSC663284, BVT948, and ryuvidine) were validated as potent SETD8 inhibitors. These compounds contain different structural motifs and inhibit SETD8 via distinct modes. More importantly, these compounds show cellular activity by suppressing the H4K20me1 mark of SETD8 and recapitulate characteristic S/G2/M phase cell cycle defects as observed for RNAi-mediated SETD8 knockdown. The commonality of SPS8I1-3 against SETD8, together with their distinct structures and mechanisms for SETD8 inhibition, argues for the collective application of these compounds as SETD8 inhibitors. PMID- 25137014 TI - New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides de novo and enables accurate false discovery rate analysis for small data sets. AB - Glycoproteins are biologically significant large molecules that participate in numerous cellular activities. In order to obtain site-specific protein glycosylation information, intact glycopeptides, with the glycan attached to the peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods such as collision-induced dissociation (CID) and electron transfer dissociation (ETD). While several emerging automated tools are developed, no consensus is present in the field about the best way to determine the reliability of the tools and/or provide the false discovery rate (FDR). A common approach to calculate FDRs for glycopeptide analysis, adopted from the target-decoy strategy in proteomics, employs a decoy database that is created based on the target protein sequence database. Nonetheless, this approach is not optimal in measuring the confidence of N-linked glycopeptide matches, because the glycopeptide data set is considerably smaller compared to that of peptides, and the requirement of a consensus sequence for N-glycosylation further limits the number of possible decoy glycopeptides tested in a database search. To address the need to accurately determine FDRs for automated glycopeptide assignments, we developed GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying glycopeptides without using a decoy database. GPE generates decoy glycopeptides de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. The decoys, along with target glycopeptides, are scored against the ETD data, from which FDRs can be calculated accurately based on the number of decoy matches and the ratio of the number of targets to decoys, for small data sets. GPE is freely accessible for download and can work with any search engine that interprets ETD data of N-linked glycopeptides. The software is provided at https://desairegroup.ku.edu/research. PMID- 25137016 TI - Recent developments in transition metal-catalysed spiroketalisation. AB - The spiroketal motif occurs in a wide range of biologically active natural products and represents a valuable target in medicinal chemistry and total synthesis. In recent years, innovative new synthetic methods have substantially expanded the range of potential precursors, cyclisation modes and opportunities for asymmetric catalysis and tandem processes. This Perspective aims to highlight recent rapid advances in the use of transition metal catalysis for spiroketal formation, in the context of our own investigations into gold-catalysed asymmetric spiroketalisation. PMID- 25137015 TI - Synthesis of aliphatic sulfur pentafluorides by oxidation of SF5-containing anisole, phenols, and anilines. AB - 4-(Pentafluorosulfanyl)catechol, 2-amino-4-(pentafluorosulfanyl)phenol, and 2 amino-5-(pentafluorosulfanyl)phenol undergo oxidation by lead tetraacetate at ambient temperature leading to dearomatization and the formation of SF5 substituted nitriles and esters of cis,cis-hexa-2,4-dienedioic (muconic) acid in good yields. 4-(Pentafluorosulfanyl)phenol and 4-(pentafluorosulfanyl)anisole are oxidized by 30% aqueous hydrogen peroxide in concentrated sulfuric acid to provide 2-(5-oxo-3-(pentafluorosulfanyl)-2,5-dihydrofuran-2-yl)acetic acid [3 (pentafluorosulfanyl)muconolactone] and small amounts of side products--SF5 containing maleic and succinic acids. The methods presented are the first examples of the practical synthesis of aliphatic SF5-containing compounds from readily available aromatic ones. PMID- 25137017 TI - Key role of dual specificity kinase TTK in proliferation and survival of pancreatic cancer cells. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive human malignancies with an overall 5-year survival rate of <5%. Despite significant advances in treatment of the disease during the past decade, the median survival rate (~6 months) has hardly improved, warranting the need to identify novel targets for therapeutic approaches. METHODS: Quantitative real time PCR, western blot analyses and immunohistochemical staining of tissue microarrays were used to analyse the expression of TTK gene in primary PDAC tissues and cell lines. To inhibit TTK kinase expression in a variety of pancreatic cancer cell lines, RNA interference was used. Functional roles of this kinase in the context of PDAC were studied using cell proliferation, viability and anchorage-independent growth assays. Western blotting, fluorescence-activated cell sorting analyses and fluorescence microscopy were used to gain mechanistic insight into the functional effects. CONCLUSIONS: We show that the dual specificity kinase TTK (also known as Mps1), is strongly overexpressed in human PDAC. Functionally, cell proliferation was significantly attenuated following TTK knockdown, whereas apoptosis and necrosis rates were significantly increased. In addition, anchorage-independent growth, a hallmark of malignant transformation and metastatic potential, was strongly impaired in the absence of TTK gene function. Interestingly, immortalised normal pancreatic hTERT-HPNE cells were not affected by loss of TTK function. Mechanistically, these effects in cancer cells were associated with increased formation of micronuclei, suggesting that loss of TTK function in pancreatic cancer cells results in chromosomal instability and mitotic catastrophe. Taken together, our data show that TTK function is critical for growth and proliferation of pancreatic cancer cells, thus establishing this kinase as an interesting new target for novel therapeutic approaches in combating this malignancy. PMID- 25137019 TI - Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers. AB - BACKGROUND: Endostatin, a fragment of collagen XVIII, is an endogenous angiogenesis inhibitor with anti-tumour functions. However, elevated circulating endostatin concentrations have been found in several human cancers including colorectal cancer (CRC). METHODS: Serum endostatin levels were measured by enzyme linked immunoassay from a series of 143 patients with CRC and from 84 controls, and correlated with detailed clinicopathological features of CRC, serum leukocyte differential count and C-reactive protein (CRP) levels. RESULTS: Patients with CRC had higher serum endostatin levels than the controls (P=0.005), and high levels associated with age, tumour invasion through the muscularis propria and poor differentiation, but not with metastases. Endostatin levels showed a positive correlation with the markers of systemic inflammatory response and a negative correlation with the densities of tumour-infiltrating mast cells and dendritic cells. Collagen XVIII was expressed in tumour stroma most strikingly in blood vessels and capillaries, and in the muscle layer of the bowel wall. CONCLUSIONS: Elevated endostatin levels in CRC correlate with systemic inflammation and invasion through the muscularis propria. Increased endostatin level may be a result of invasion-related cleavage of collagen XVIII expressed in the bowel wall. The negative correlations between serum endostatin and intratumoural mast cells and immature dendritic cells may reflect angiogenesis inhibition by endostatin. PMID- 25137018 TI - Urinary TIMP-1 and MMP-2 levels detect the presence of pancreatic malignancies. AB - BACKGROUND: A majority of patients with pancreatic malignancies, including both pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumours (pNETs), present with advanced disease due to a lack of specific symptoms and current diagnostic limitations, making this disease extremely difficult to detect. Our goal was to determine whether urinary matrix metalloproteases (uMMPs) and/or their endogenous inhibitors, urinary tissue inhibitor of metalloproteases (uTIMPs), could be detected in the urine of patients with pancreatic malignancies and whether they may serve as independent predictors of disease status. METHODS: Retrospective analyses of urine samples (n=139) from PDAC and pNET patients as well as age- and sex-matched controls were conducted. Urinary MMP-2 and uTIMP-1 levels were determined using ELISA and zymography. Biomarker expression in tumour and normal pancreatic tissues was analysed via immunohistochemistry (IHC). RESULTS: Multivariable logistic regression analyses indicated that, when controlling for age and sex, uMMP-2 (P<0.0001) and uTIMP-1 (P<0.0001) but not uMMP-9, were significant independent predictors for distinguishing between PDAC patients and healthy controls. Our data also indicated that uMMP-2 was an independent predictor of the presence of pNET. In addition, uTIMP-1 levels could differentiate the two cancer groups, PDAC and pNET, respectively. Immunohistochemistry analysis confirmed that MMP-2 and TIMP-1 protein expression is significantly upregulated in PDAC tissue compared with the normal pancreas. CONCLUSIONS: Taken together, our results suggest that the detection of uMMP-2 and uTIMP-1 may have diagnostic value in the detection of pancreatic malignancies and that uTIMP-1 may be useful in distinguishing between pancreatic adenocarcinoma and neuroendocrine tumours. PMID- 25137023 TI - Probing the optical property and electronic structure of TiO2 nanomaterials for renewable energy applications. PMID- 25137021 TI - Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and survival following surgery. AB - BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell carcinoma (ccRCC) are limited owing to the lack of validation and consensus for interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim of this study was to analytically validate the applicability of I-FISH in assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic impact following surgical excision of ccRCC. METHODS: Tissue microarrays were constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks. Interphase fluorescent in situ hybridisation analysis was undertaken based on preset criteria by two independent observers to assess interobserver variability. 9p status in ccRCC tumours was determined and correlated to clinicopathological variables, recurrence-free survival and disease-specific survival. RESULTS: There were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa statistic for interobserver variability was 0.71 (good agreement). 9p deletion was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN (stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On multivariate analysis, 9p deletion was an independent predictor of recurrence (hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603; P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is associated with aggressive ccRCC and worse prognosis in patients following surgery. Our findings independently confirm the findings of previous reports relying on I-FISH to detect 9p (CDKN2A) deletion. PMID- 25137020 TI - Phorbol ester stimulates ethanolamine release from the metastatic basal prostate cancer cell line PC3 but not from prostate epithelial cell lines LNCaP and P4E6. AB - BACKGROUND: Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethanolamine (Etn) metabolites released to the medium. METHODS: Prostate epithelial cell lines P4E6, LNCaP and PC3 were models of prostate cancer (PCa). PNT2C2 and PNT1A were models of benign prostate epithelia. Cellular EtnPGs were labelled with [1-(3)H]-Etn hydrochloride. PKC was activated with phorbol ester (TPA) and inhibited with Ro31-8220 and GF109203X. D609 was used to inhibit PLD (phospholipase D). [(3)H]-labelled Etn metabolites were resolved by ion-exchange chromatography. Sodium oleate and mastoparan were tested as activators of PLD2. Phospholipase D activity was measured by a transphosphatidylation reaction. Cells were treated with ionomycin to raise intracellular Ca(2+) levels. RESULTS: Unstimulated cell lines release mainly Etn and glycerylphosphorylEtn (GPEtn) to the medium. Phorbol ester treatment over 3h increased Etn metabolite release from the metastatic PC3 cell line and the benign cell lines PNT2C2 and PNT1A but not from the tumour-derived cell lines P4E6 and LNCaP; this effect was blocked by Ro31-8220 and GF109203X as well as by D609, which inhibited PLD in a transphosphatidylation reaction. Only metastatic PC3 cells specifically upregulated Etn release in response to TPA treatment. Oleate and mastoparan increased GPEtn release from all cell lines at the expense of Etn. Ionomycin stimulated GPEtn release from benign PNT2C2 cells but not from cancer-derived cell lines P4E6 or PC3. Ethanolamine did not stimulate the proliferation of LNCaP or PC3 cell lines but decreased the uptake of choline (Cho). CONCLUSIONS: Only the metastatic basal PC3 cell line specifically increased the release of Etn on TPA treatment most probably by PKC activation of PLD1 and increased turnover of EtnPGs. The phosphatidic acid formed will maintain a cancer phenotype through the regulation of mTOR. Ethanolamine released from cells may reduce Cho uptake, regulating the membrane PtdEtn:PtdCho ratio and influencing the action of PtdEtn binding proteins such as RKIP and the anti-apoptotic hPEBP4. The work highlights a difference between LNCaP cells used as a model of androgen-dependent early stage PCa and androgen-independent PC3 cells used to model later refractory stage disease. PMID- 25137024 TI - Ab initio study of potential ultrafast internal conversion routes in oxybenzone, caffeic acid, and ferulic acid: implications for sunscreens. AB - Oxybenzone (OB) and ferulic acid (FA) both find use in commercial sunscreens; caffeic acid (CA) differs from FA by virtue of an -OH group in place of a -OCH3 group on the aromatic ring. We report the results of ab initio calculations designed to explore the excited state nonradiative relaxation pathways that provide photostability to these molecules and the photoprotection they offer toward UV-A and UV-B radiation. In the case of OB, internal conversion (IC) is deduced to occur on ultrafast time scales, via a barrierless electron-driven H atom transfer pathway from the S1(1(1)npi*) state to a conical intersection (CI) with the ground (S0) state potential energy surface (PES). The situation with respect to CA and FA is somewhat less clear-cut, with low energy CIs identified by linking excited states to the S0 state following photoexcitation and subsequent evolution along (i) a ring centered out-of-plane deformation coordinate, (ii) the E/Z isomerism coordinate and, in the case of CA, (iii) an O H stretch coordinate. Analogy with catechol suggests that the last of these processes (if active) would lead to radical formation (and thus potential phototoxicity), encouraging a suggestion that FA might be superior to CA as a sunscreen ingredient. PMID- 25137022 TI - Cost-effectiveness of alternative strategies for integrating MRI into breast cancer screening for women at high risk. AB - BACKGROUND: Magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer. We evaluated the cost-effectiveness of alternative screening strategies involving MRI. METHODS: Using a microsimulation model, we generated life histories under different risk profiles, and assessed the impact of screening on quality-adjusted life-years, and lifetime costs, both discounted at 3%. We compared 12 screening strategies combining annual or biennial MRI with mammography and clinical breast examination (CBE) in intervals of 0.5, 1, or 2 years vs without, and reported incremental cost-effectiveness ratios (ICERs). RESULTS: Based on an ICER threshold of $100,000/QALY, the most cost-effective strategy for women at 25% lifetime risk was to stagger MRI and mammography plus CBE every year from age 30 to 74, yielding ICER $58,400 (compared to biennial MRI alone). At 50% lifetime risk and with 70% reduction in MRI cost, the recommended strategy was to stagger MRI and mammography plus CBE every 6 months (ICER=$84,400). At 75% lifetime risk, the recommended strategy is biennial MRI combined with mammography plus CBE every 6 months (ICER=$62,800). CONCLUSIONS: The high costs of MRI and its lower specificity are limiting factors for annual screening schedule of MRI, except for women at sufficiently high risk. PMID- 25137025 TI - Somatotropinomas, but not nonfunctioning pituitary adenomas, maintain a functional apoptotic RET/Pit1/ARF/p53 pathway that is blocked by excess GDNF. AB - Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPalpha) consensus binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPalpha site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in acromegaly. PMID- 25137026 TI - Triiodothyronine prevents cardiac ischemia/reperfusion mitochondrial impairment and cell loss by regulating miR30a/p53 axis. AB - Mitochondrial dysfunctions critically affect cardiomyocyte survival during ischemia/reperfusion (I/R) injury. In this scenario p53 activates multiple signaling pathways that impair cardiac mitochondria and promote cell death. p53 is a validated target of miR-30 whose levels fall under ischemic conditions. Although triiodothyronine (T3) rescues post-ischemic mitochondrial activity and cell viability, no data are available on its role in the modulation of p53 signaling in I/R. Here we test the hypothesis that early T3 supplementation in rats inhibits the post I/R activation of p53 pro-death cascade through the maintenance of miRNA 30a expression. In our model, T3 infusion improves the recovery of post-ischemic cardiac performance. At the molecular level, the beneficial effect of T3 is associated with restored levels of miR-30a expression in the area at risk (AAR) that correspond to p53 mRNA downregulation. The concomitant decrease in p53 protein content reduces Bax expression and limits mitochondrial membrane depolarization resulting in preserved mitochondrial function and decreased apoptosis and necrosis extent in the AAR. Also in primary cardiomyocyte culture of neonatal rats, T3 prevents both miR-30a downregulation and p53 raise induced by hypoxia. The regulatory effect of T3 is greatly suppressed by miR-30a knockdown. Overall these data suggest a new mechanism of T3 mediated cardioprotection that is targeted to mitochondria and acts, at least in part, through the regulation of miR-30a/p53 axis. PMID- 25137028 TI - Progesterone induces RhoA Inactivation in male rat aortic smooth muscle cells through up-regulation of p27(kip1.). AB - Previously, we showed that progesterone (P4) at physiologic concentrations (5nM 500nM) inhibits proliferation and migration of rat aortic smooth muscle cells (RASMCs). The P4-induced migration inhibition in RASMC was resulted from Rat sacroma homolog gene family, member A (RhoA) inactivation induced by activating the cSrc/AKT/ERK 2/p38 mitogen-activated protein kinase-mediated signaling pathway. We also demonstrated that up-regulation of cyclin-dependent kinase inhibitor 1B (p27(kip1)) is involved in the P4-induced migration inhibition in RASMC. Because P4 can increase formation of the p27(kip1)-RhoA complex in RASMC, this finding led us to hypothesize that the P4-induced inactivation in RhoA might be caused by up-regulation of p27(kip1). Here, we showed that P4 increased phosphorylation of p27(kip1) at Ser10 in the nucleus, which in turn caused p27(kip1) translocation from the nucleus to the cytosol, subsequently increasing formation of the p27(kip1)-RhoA complex. These effects were blocked by knocking down kinase-interacting stathmin (KIS) using KIS small interfering RNA. Knock down of p27(kip1) abolished the P4-induced decreases in the level of RhoA protein in RASMC. However, pretreatment of RASMC with the proteasome inhibitor, N (benzyloxycarbonyl)leucinylleucinylleucinal (MG132), prevented the P4-induced degradation of p27(kip1) and RhoA. Taken together, our investigation of P4 induced migration inhibition in RASMC showed a sequence of associated intracellular events that included 1) increase in formation of the KIS-p27(kip1) complex in the nucleus; 2) phosphorylated nuclear p27(kip1) at Ser10; 3) increased cytosolic translocation of p27(kip1) and formation of the p27(kip1) RhoA complex in the cytosol; and 4) degradation of p27(kip1) and RhoA through the ubiquitin-proteasome pathway. These findings highlight the molecular mechanisms underlying P4-induced migration inhibition in RASMC. PMID- 25137027 TI - Role of melanocortin signaling in neuroendocrine and metabolic actions of leptin in male rats with uncontrolled diabetes. AB - Although the antidiabetic effects of leptin require intact neuronal melanocortin signaling in rodents with uncontrolled diabetes (uDM), increased melanocortin signaling is not sufficient to mimic leptin's glucose-lowering effects. The current studies were undertaken to clarify the role of melanocortin signaling in leptin's ability to correct metabolic and neuroendocrine disturbances associated with uDM. To accomplish this, bilateral cannulae were implanted in the lateral ventricle of rats with streptozotocin-induced diabetes, and leptin was coinfused with varying doses of the melanocortin 3/4 receptor (MC3/4R) antagonist, SHU9119. An additional cohort of streptozotocin-induced diabetes rats received intracerebroventricular administration of either the MC3/4R agonist, melanotan II, or its vehicle. Consistent with previous findings, leptin's glucose-lowering effects were blocked by intracerebroventricular SHU9119. In contrast, leptin mediated suppression of hyperglucagonemia involves both melanocortin dependent and independent mechanisms, and the degree of glucagon inhibition was associated with reduced plasma ketone body levels. Increased central nervous system melanocortin signaling alone fails to mimic leptin's ability to correct any of the metabolic or neuroendocrine disturbances associated with uDM. Moreover, the inability of increased melanocortin signaling to lower diabetic hyperglycemia does not appear to be secondary to release of the endogenous MC3/4R inverse agonist, Agouti-related peptide (AgRP), because AgRP knockout mice did not show increased susceptibility to the antidiabetic effects of increased MC3/4R signaling. Overall, these data suggest that 1) AgRP is not a major driver of diabetic hyperglycemia, 2) mechanisms independent of melanocortin signaling contribute to leptin's antidiabetic effects, and 3) melanocortin receptor blockade dissociates leptin's glucose-lowering effect from its action on other features of uDM, including reversal of hyperglucagonemia and ketosis, suggesting that brain control of ketosis, but not blood glucose levels, is glucagon dependent. PMID- 25137030 TI - Calculating hominin and nonhuman anthropoid femoral head diameter from acetabular size. AB - Femoral head size provides important information on body size in extinct species. Although it is well-known that femoral head size is correlated with acetabular size, the precision with which femoral head size can be estimated from acetabular size has not been quantified. The availability of accurate 3D surface models of fossil acetabular remains opens the possibility of obtaining accurate estimates of femoral head size from even fragmentary fossil remains [Hammond et al.,: Am J Phys Anthropol 150 (2013) 565-578]. Here we evaluate the relationship between spheres fit to surface models of the femoral head and acetabulum of a large sample of extant anthropoid primates. Sphere diameters are tightly correlated and scale isometrically. In spite of significant taxonomic and possibly functional differences in the relationship between femoral head size and acetabulum size, percent prediction errors of estimated femoral head size remain low regardless of the taxonomic composition of the reference sample. We provide estimates of femoral head size for a series of fossil hominins and monkeys. PMID- 25137029 TI - In vivo fluorescence imaging and urinary monoamines as surrogate biomarkers of disease progression in a mouse model of pheochromocytoma. AB - Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor arising from catecholamine-producing chromaffin cells. Especially for metastatic PHEO, the availability of animal models is essential for developing novel therapies. For evaluating therapeutic outcome in rodent PHEO models, reliable quantification of multiple organ lesions depends on dedicated small-animal in vivo imaging, which is still challenging and only available at specialized research facilities. Here, we investigated whether whole-body fluorescence imaging and monitoring of urinary free monoamines provide suitable parameters for measuring tumor progression in a murine allograft model of PHEO. We generated an mCherry-expressing mouse PHEO cell line by lentiviral gene transfer. These cells were injected subcutaneously into nude mice to perform whole-body fluorescence imaging of tumor development. Urinary free monoamines were measured by liquid chromatography with tandem mass spectrometry. Tumor fluorescence intensity and urinary outputs of monoamines showed tumor growth-dependent increases (P < .001) over the 30 days of monitoring post-tumor engraftment. Concomitantly, systolic blood pressure was increased significantly during tumor growth. Tumor volume correlated significantly (P < .001) and strongly with tumor fluorescence intensity (rs = 0.946), and urinary outputs of dopamine (rs = 0.952), methoxytyramine (rs = 0.947), norepinephrine (rs = 0.756), and normetanephrine (rs = 0.949). Dopamine and methoxytyramine outputs allowed for detection of lesions at diameters below 2.3 mm. Our results demonstrate that mouse pheochromocytoma (MPC)-mCherry cell tumors are functionally similar to human PHEO. Both tumor fluorescence intensity and urinary outputs of free monoamines provide precise parameters of tumor progression in this sc mouse model of PHEO. This animal model will allow for testing new treatment strategies for chromaffin cell tumors. PMID- 25137031 TI - Antidiabetic potentials of essential oil extracted from the leaves of Hoslundia opposita Vahl. AB - This study was aimed at assessing the potential of essential oil from the leaf of Hoslundia opposita in the treatment of diabetes. Forty-eight rats (Rattus norvegicus) were randomized into two groups; nondiabetic and diabetic groups, each with four subgroups. Animals in the diabetic group were induced with diabetes using a single dose of alloxan monohydrate, 160 mg/kg body weight (b. wt.). The rats were treated with 110 and 220 mg/kg b. wt. of the essential oil. All treatments were administered, intraperitoneally, once a day for 4 days. In the nondiabetic condition, there was no effect of the oil on fasting blood glucose (FBG) levels in rats. In diabetic rats, the oil caused a significant reduction in FBG levels. Treatment with 110 mg/kg b. wt. of the oil reduced FBG almost to the normoglycemic level by day 4 and the overall glucose excursion during a 3-h intraperitoneal glucose tolerance test approached the baseline level at 120 min. Also, hepatic glycogen was significantly higher, while the glucose concentrations were lower in the diabetic-treated group when compared with the diabetic untreated group. Histological examinations revealed a mildly distorted architecture of the pancreatic islets beta-cells of diabetic rats treated with the oil, while those of the untreated rats were severely degenerated. Overall, the in vivo antihyperglycemic activity of the essential oil may prove to be of clinical importance in the management of type 2 diabetes. PMID- 25137032 TI - Multicomponent diffusion in solute-containing micelle and microemulsion solutions. AB - Holographic interferometry was used to obtain new results for the four coefficients that determine rates of multicomponent diffusion of hydrophobic solutes and surfactants in microemulsions. The three solutes pentanol, octanol, and heptane were examined in microemulsions formed from decaethylene glycol monododecyl ether (C12E10) and sodium dodecyl sulfate (SDS). These coefficients are compared with relevant binary and effective binary diffusion coefficients, and also with ternary diffusion coefficients reported in the literature. It is shown that a strong coupling exists between the diffusion of hydrophobic solutes and surfactant in solute-containing microemulsions. In particular, the presence of a gradient in the concentration of the solute can induce a surprisingly large flux of surfactant either up or down the solute gradient. Within the framework of irreversible thermodynamics, these results indicate that hydrophobic solute molecules significantly alter the chemical potential of the surfactant in microemulsions. These effects are present to a comparable degree for both the nonionic C12E10 and ionic SDS microemulsions. PMID- 25137036 TI - Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. AB - AIM: This study evaluated the effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. METHODS: A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients with diagnosis of metabolic syndrome in accordance with the International Diabetes Federation criteria. Glucose and insulin levels were measured after a 75 gram dextrose load. Triglycerides and high-density lipoprotein cholesterol concentrations at baseline were also evaluated. Twelve patients received trans resveratrol (500 mg) three times per day before meals for 90 days. The remaining 12 patients received placebo at the same dose. The area under the curve (AUC) values of glucose and insulin, total insulin secretion, first-phase of insulin secretion, and insulin sensitivity were calculated. RESULTS: After resveratrol administration, there were significant differences in total weight (94.4+/-13.2 vs. 90.5+/-12.3 kg, P=0.007), body mass index (BMI) (35.6+/-3.2 vs. 34.3+/-3.0 kg/m(2), P=0.006), fat mass (41.2+/-7.9 vs. 38.8+/-6.0 kg, P=0.001), and waist circumference (WC) (109+/-9 vs. 105+/-10 cm, P=0.004). There were also significant differences in AUC of insulin (48,418+/-22,707 vs. 26,473+/-8,273 pmol/L, P=0.003) and insulinogenic index (0.48+/-0.22 vs. 0.28+/-0.08, P=0.004). CONCLUSIONS: Administration of resveratrol significantly decreases weight, BMI, fat mass, WC, AUC of insulin, and total insulin secretion. PMID- 25137033 TI - Recognition and management of delirium among doctors, nurses, physiotherapists, and psychologists: an Italian survey. AB - BACKGROUND: There are no studies that have identified the ability to recognize and manage delirium among Italian health providers caring for patients at risk. Therefore, the Italian Association of Psychogeriatrics (AIP) conducted a multicenter survey among doctors, nurses, psychologists and physiotherapists to assess their competence regarding the theme of delirium and its management in the everyday clinical practice. METHODS: The survey period was 1st June 2013 to 30th November 2013. The invitation to participate was sent via email, with publication on the AIP website. The survey included 14 questions and two case vignettes. RESULTS: A total of 648/1,500 responses were collected. Most responders were doctors (n = 322/800), followed by nurses (n = 225/500), psychologists (n = 51/100), and physiotherapists (n = 30/100). Generally, doctors and psychologists correctly defined delirium, while nurses and physiotherapists did not. The most frequently used diagnostic tools were the Confusion Assessment Method (CAM) and the Diagnostic and Statistical Manual of Mental Disorders-IV. Delirium intensity was rarely assessed. Hypoactive delirium was generally managed with non pharmacological approaches, while hyperactive delirium with a combination of non pharmacological and pharmacological approaches. However, possible causes of delirium were under-assessed by half of doctors and by the majority of other professionals. Nurses, psychologists and physiotherapists did not answer the case vignettes, while doctors identified the correct answer in most cases. CONCLUSIONS: This is the first Italian survey among health providers caring for patients at risk of delirium. This is also the first survey including doctors, nurses, psychologists and physiotherapists. The results emphasize the importance of training to improve knowledge of this relevant unmet medical need. PMID- 25137035 TI - Evidence for the presence of novel beta-melatonin receptors along with classical alpha-melatonin receptors in the fish Rasbora daniconius (Ham.). AB - The effects of melatonin (MT) were examined on the isolated scale melanophores from dorso-lateral (D-L) and band regions of a tropical fish Rasbora daniconius. Our study primarily aimed for further depiction of the signaling receptors involved in MT mediated pigment translocations in the fish. Melanophore Size Index (MSI) was employed as a recording parameter for the responses of melanophores to MT and various antagonists. MT has induced aggregation as well as dispersion in D-L region and aggregation in band region melanophores during summer season. During winter, MT-induced responses were only of aggregatory type in D-L region, while in the band region there was an increase in the sensitivity. The responses of the melanophores to MT were reversible. The aggregation of innervated melanophores induced by MT on the D-L and band regions was partially mediated through the neurotransmitters released under the influence of MT and partially by the specific MT receptors. Luzindole and K185 have completely blocked the aggregatory responses of D-L and band region melanophores. Aggregatory receptors may be of the conventional alpha-MT type. Dispersion of D-L and band region melanophores induced by MT in the presence of various antagonists and on denervated band region could be the result of activation of beta-MT receptors of dispersive nature. Presence of alpha and beta MT receptors is thus indicated in this fish melanophores. PMID- 25137037 TI - Modulation of chemotherapeutic drug resistance in neuroblastoma SK-N-AS cells by the neural apoptosis inhibitory protein and miR-520f. AB - The acquisition of multidrug resistance is a major impediment to the successful treatment of neuroblastoma, a clinically heterogeneous cancer accounting for ~15% of all pediatric cancer deaths. The MYCN transcription factor, whose gene is amplified in ~30% of high-risk neuroblastoma cases, influences drug resistance by regulating a cadre of genes, including those involved with drug efflux, however, other high-risk subtypes of neuroblastoma lacking MYCN amplification, such as those with chromosome 11q deletions, also acquire multidrug resistance. To elucidate additional mechanisms involved with drug resistance in non-MYCN amplified tumour cells, an SK-N-AS subline (SK-N-AsCis24) that is significantly resistant to cisplatin and cross resistant to etoposide was developed through a pulse-selection process. High resolution aCGH analysis of SK-N-AsCis24 revealed a focal gain on chromosome 5 containing the coding sequence for the neural apoptosis inhibitory protein (NAIP). Significant overexpression of NAIP mRNA and protein was documented, while experimental modulation of NAIP levels in both SK-N AsCis24 and in parental SK-N-AS cells confirmed that NAIP was responsible for the drug resistant phenotype by apoptosis inhibition. Furthermore, a decrease in the NAIP targeting microRNA, miR-520f, was also demonstrated to be partially responsible for increased NAIP levels in SK-N-AsCis24. Interestingly, miR-520f levels were determined to be significantly lower in postchemotherapy treatment tumours relative to matched prechemotherapy samples, consistent with a role for this miRNA in the acquisition of drug resistance in vivo, potentially through decreased NAIP targeting. Our findings provide biological novel insight into neuroblastoma drug-resistance and have implications for future therapeutic research. PMID- 25137038 TI - Identification of conserved and novel microRNAs in the Pacific oyster Crassostrea gigas by deep sequencing. AB - MicroRNAs (miRNAs) play important roles in regulatory processes in various organisms. To date many studies have been performed in the investigation of miRNAs of numerous bilaterians, but limited numbers of miRNAs have been identified in the few species belonging to the clade Lophotrochozoa. In the current study, deep sequencing was conducted to identify the miRNAs of Crassostrea gigas (Lophotrochozoa) at a genomic scale, using 21 libraries that included different developmental stages and adult organs. A total of 100 hairpin precursor loci were predicted to encode miRNAs. Of these, 19 precursors (pre miRNA) were novel in the oyster. As many as 53 (53%) miRNAs were distributed in clusters and 49 (49%) precursors were intragenic, which suggests two important biogenetic sources of miRNAs. Different developmental stages were characterized with specific miRNA expression patterns that highlighted regulatory variation along a temporal axis. Conserved miRNAs were expressed universally throughout different stages and organs, whereas novel miRNAs tended to be more specific and may be related to the determination of the novel body plan. Furthermore, we developed an index named the miRNA profile age index (miRPAI) to integrate the evolutionary age and expression levels of miRNAs during a particular developmental stage. We found that the swimming stages were characterized by the youngest miRPAIs. Indeed, the large-scale expression of novel miRNAs indicated the importance of these stages during development, particularly from organogenetic and evolutionary perspectives. Some potentially important miRNAs were identified for further study through significant changes between expression patterns in different developmental events, such as metamorphosis. This study broadened the knowledge of miRNAs in animals and indicated the presence of sophisticated miRNA regulatory networks related to the biological processes in lophotrochozoans. PMID- 25137039 TI - Enhanced cross-presentation and improved CD8+ T cell responses after mannosylation of synthetic long peptides in mice. AB - The use of synthetic long peptides (SLP) has been proven to be a promising approach to induce adaptive immune responses in vaccination strategies. Here, we analyzed whether the efficiency to activate cytotoxic T cells by SLP-based vaccinations can be increased by conjugating SLPs to mannose residues. We could demonstrate that mannosylation of SLPs results in increased internalization by the mannose receptor (MR) on murine antigen-presenting cells. MR-mediated internalization targeted the mannosylated SLPs into early endosomes, from where they were cross-presented very efficiently compared to non-mannosylated SLPs. The influence of SLP mannosylation was specific for cross-presentation, as no influence on MHC II-restricted presentation was observed. Additionally, we showed that vaccination of mice with mannosylated SLPs containing epitopes from either ovalbumin or HPV E7 resulted in enhanced proliferation and activation of antigen specific CD8+ T cells. These findings demonstrate that mannosylation of SLPs augments the induction of a cytotoxic T cell response in vitro and in vivo and might be a promising approach to induce cytotoxic T cell responses in e.g. cancer therapy and anti-viral immunity. PMID- 25137040 TI - Comparison of interferon-gamma release assay to two cut-off points of tuberculin skin test to detect latent Mycobacterium tuberculosis infection in primary health care workers. AB - BACKGROUND: An interferon-gamma release assay, QuantiFERON-TB (QFT) test, has been introduced an alternative test for the diagnosis of latent Mycobacterium tuberculosis infection (LTBI). Here, we compared the performance of QFT with tuberculin skin test (TST) measured at two different cut-off points among primary health care work (HCW) in Brazil. METHODS: A cross-sectional study was carried out among HCWs in four Brazilian cities with a known history of high incidence of TB. Results of the QFT were compared to TST results based on both >=5 mm and >=10 mm as cut-off points. RESULTS: We enrolled 632 HCWs. When the cut-off value of >=10 mm was used, agreement between QFT and TST was 69% (k = 0.31), and when the cut-off of >=5 mm was chosen, the agreement was 57% (k = 0.22). We investigated possible factors of discordance of TST vs QFT. Compared to the TST-/QFT- group, risk factors for discordance in the TST+/QFT- group with TST cut-off of >=5 mm included age between 41-45 years [OR = 2.70; CI 95%: 1.32-5.51] and 46-64 years [OR = 2.04; CI 95%: 1.05-3.93], BCG scar [OR = 2.72; CI 95%: 1.40-5.25], and having worked only in primary health care [OR = 2.30; CI 95%: 1.09-4.86]. On the other hand, for the cut-off of >=10 mm, BCG scar [OR = 2.26; CI 95%: 1.03-4.91], being a household contact of a TB patient [OR = 1.72; CI 95%: 1.01-2.92] and having had a previous TST [OR = 1.66; CI 95%: 1.05-2.62], were significantly associated with the TST+/QFT- group. No statistically significant associations were found among the TST-/QFT+ discordant group with either TST cut-off value. CONCLUSIONS: Although we identified BCG vaccination to contribute to the discordance at both TST cut-off measures, the current Brazilian recommendation for the initiation of LTBI treatment, based on information gathered from medical history, TST, chest radiograph and physical examination, should not be changed. PMID- 25137041 TI - Expression of STAT5, COX-2 and PIAS3 in correlation with NSCLC histhopathological features. AB - Signal transducers and activators of transcription (STATs), their inhibitors and cyclooxygenase-2 (COX-2) participate in transformations of many various types of cancers. The aim of the present study was to evaluate the relationship between STAT5A/B, COX-2, and PIAS3 mRNA expression and tumor staging, metastasis status, and histopathological subtype in 71 patients with confirmed non-small cell lung cancer (NSCLC) diagnosis. Total RNA was isolated from NSCLC tissue samples and the expression of the studied genes was assessed using TaqMan probes in real-time PCR assay. The expression levels of STAT5A, STAT5B, and COX-2 genes were increased in 69%, 79%, and 71% NSCLC samples respectively, while PIAS3 expression was decreased in the majority (69%) of the studied tissues. Statistically significant differences were observed between STAT5 isoforms (P = 0.0008), with higher expression of STAT5B. We found statistically significant positive correlation between STAT5B and COX-2 (rho = 0.045), and significant negative correlation between STAT5B and PIAS3 (rho = -0.049). The negative correlation between STAT5B and PIAS3 (rho = -0.43) was also observed in T2a+T2b tumor group. Additionally, STAT5B and COX-2 expression levels were significantly different between T1a+T1b and T2a+T2b tumors (P = 0.002 and P = 0.041, respectively), with higher expression of both genes in T2 tumor stage. PIAS3 expression was significantly lower in NSCC subtype as compared with SCC subtype (P = 0.017). Also, STAT5A and STAT5B immunoexpression was assessed, and the results indicated significantly higher protein levels in NSCLC patients as compared with controls (P = 0.048 and P = 0.034, respectively). High STAT5B immunoexpression was positively correlated with STAT5B gene expression in tumors (rho = 0.755). STAT5B protein level was also significantly higher in T2a+T2b tumors, reflecting high STAT5B gene expression in this group. There was no statistically significant association between mRNA and protein expression levels of the studied genes and patients' characteristics: age, gender, smoking. The obtained results highlight the importance of the genes STAT5B and COX-2 in lung cancer progression. PMID- 25137042 TI - Oligomerization mechanisms of an H-NS family protein, Pmr, encoded on the plasmid pCAR1 provide a molecular basis for functions of H-NS family members. AB - Enterobacterial H-NS-like proteins and Pseudomonas MvaT-like proteins share low homology at the amino acid sequence level, but both can function as xenogeneic silencers and are included in the H-NS family of proteins. H-NS family members have dimerization/oligomerization and DNA-binding domains connected by a flexible linker and form large nucleoprotein complexes using both domains. Pmr, an MvaT like protein encoded on the IncP-7 carbazole-degradative plasmid pCAR1, is a key regulator of an interaction between pCAR1 and its host Pseudomonas putida KT2440. KT2440 has two transcribed genes that encode the MvaT-like proteins TurA and TurB. Our previous transcriptome analyses suggested that the functions of Pmr, TurA and TurB are non-equivalent, although the detailed underlying mechanisms remain unclear. In this study, we focused on the protein-protein interactions of Pmr, and assessed the homo-oligomerization capacity of various substituted and truncated Pmr derivatives by protein-protein cross-linking analysis. Six of the seven residues identified as important for homo-oligomerization in Pmr were located near the N-terminus, and the putative flexible linker or the region near that was not involved in homo-oligomerization, suggesting that Pmr homo oligomerization is different from that of enterobacterial H-NS and that the functional mechanism differs between H-NS-like and MvaT-like proteins. In addition, we assessed homo- and hetero-oligomerization of Pmr by surface plasmon resonance analysis and found that the coupling ratio of TurB-Pmr oligomers is smaller than that of Pmr-Pmr or TurA-Pmr oligomers. These results raised the possibility that composition of the hetero-oligomers of Pmr, TurA, and TurB could explain why the different gene sets were affected by either pmr, turA, or turB disruption in our previous studies. PMID- 25137046 TI - Bugs split to attack and gamble to survive. PMID- 25137044 TI - Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. AB - Glycoconjugate is one of the most efficacious and safest vaccines against bacterial pathogens. Previous studies of glycoconjugates against pathogen E. coli O157:H7 focused more on the humoral responses they elicited. However, little was known about their cellular responses. In this study, we exploited a novel approach based on bacterial protein N-linked glycosylation system to produce glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose binding protein and examined its humoral and cellular responses in BALB/c mice. The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum bactericidal antibodies including anti-E. coli O157:H7 O-antigen IgG and IgM. Interestingly, O-Ag-MBP also stimulated the secretion of anti-E. coli O157:H7 O antigen IgA in intestine. In addition, O-Ag-MBP stimulated cellular responses by recruiting Th1-biased CD4+ T cells, CD8+ T cells. Meanwhile, O-Ag-MBP induced the upregulation of Th1-related IFN-gamma and downregulation of Th2-related IL-4, and the upregulation of IFN-gamma was stimulated by MBP in a dose-dependent manner. MBP showed TLR4 agonist-like properties to activate Th1 cells as carrier protein of O-Ag-MBP. Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP produced by bacterial protein N-linked glycosylation system was able to elicit both humoral and Th1-biased cellular responses. PMID- 25137043 TI - Molecular signatures of the evolving immune response in mice following a Bordetella pertussis infection. AB - Worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. Since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. The purpose was to elucidate the kinetics of the protective immune response evolving after experimental Bordetella pertussis (B. pertussis) infection in mice. Data were collected from (i) individual analyses, i.e. microarray, flow cytometry, multiplex immunoassays, and bacterial clearance; (ii) twelve time points during the infection; and (iii) different tissues involved in the immune responses, i.e. lungs, spleen and blood. Combined data revealed detailed insight in molecular and cellular sequence of events connecting different phases (innate, bridging and adaptive) of the immune response following the infection. We detected a prolonged acute phase response, broad pathogen recognition, and early gene signatures of subsequent T-cell recruitment in the lungs. Activation of particular transcription factors and specific cell markers provided insight into the time course of the transition from innate towards adaptive immune responses, which resulted in a broad spectrum of systemic antibody subclasses and splenic Th1/Th17 memory cells against B. pertussis. In addition, signatures preceding the local generation of Th1 and Th17 cells as well as IgA in the lungs, considered key elements in protection against B. pertussis, were established. In conclusion, molecular and cellular immunological processes in response to live B. pertussis infection were unraveled, which may provide guidance in selecting new vaccine candidates that should evoke local and prolonged protective immune responses. PMID- 25137048 TI - Stress tolerance and ecophysiological ability of an invader and a native species in a seasonally dry tropical forest. AB - Ecophysiological traits of Prosopis juliflora (Sw.) DC. and a phylogenetically and ecologically similar native species, Anadenanthera colubrina (Vell.) Brenan, were studied to understand the invasive species' success in caatinga, a seasonally dry tropical forest ecosystem of the Brazilian Northeast. To determine if the invader exhibited a superior resource-capture or a resource-conservative strategy, we measured biophysical and biochemical parameters in both species during dry and wet months over the course of two years. The results show that P. juliflora benefits from a flexible strategy in which it frequently outperforms the native species in resource capture traits under favorable conditions (e.g., photosynthesis), while also showing better stress tolerance (e.g., antioxidant activity) and water-use efficiency in unfavorable conditions. In addition, across both seasons the invasive has the advantage over the native with higher chlorophyll/carotenoids and chlorophyll a/b ratios, percent N, and leaf protein. We conclude that Prosopis juliflora utilizes light, water and nutrients more efficiently than Anadenanthera colubrina, and suffers lower intensity oxidative stress in environments with reduced water availability and high light radiation. PMID- 25137047 TI - Coupling of X-chromosome reactivation with the pluripotent stem cell state. AB - X-chromosome inactivation (XCI) in female mammals is a dramatic example of epigenetic gene regulation, which entails the silencing of an entire chromosome through a wide range of mechanisms involving noncoding RNAs, chromatin modifications, and DNA-methylation. While XCI is associated with the differentiated cell state, it is reversed by X-chromosome reactivation (XCR) ex vivo in pluripotent stem cells and in vivo in the early mouse embryo and the germline. Critical in the regulation of XCI vs. XCR is the X-inactivation center, a multigene locus on the X-chromosome harboring several long noncoding RNA genes including, most prominently, Xist and Tsix. These genes, which sit at the top of the XCI hierarchy, are by themselves controlled by pluripotency factors, coupling XCR with the naive pluripotent stem cell state. In this point-of-view article we review the latest findings regarding this intricate relationship between cell differentiation state and epigenetic control of the X-chromosome. In particular, we discuss the emerging picture of complex multifactorial regulatory mechanisms, ensuring both a fine-tuned and robust X-reactivation process. PMID- 25137051 TI - Punishment based on public benefit fund significantly promotes cooperation. AB - In prisoner's dilemma game (shortly, PD game), punishment is most frequently used to promote cooperation. However, outcome varies when different punishment approaches are applied. Here the PD game is studied on a square lattice when different punishment patterns are adopted. As is known to all, tax system, a common tool to adjust the temperature of the economy, is widely used in human society. Inspired by this philosophy, players in this study would pay corresponding taxes in accordance with their payoff level. In this way, public benefit fund is established consequently and it would be utilized to punish defectors. There are two main methods for punishing: slight intensity of punishment (shortly, SLP) and severe intensity of punishment (shortly, SEP). When the totaling of public benefit fund keeps relatively fixed, SLP extends further, which means more defectors would be punished; by contrast, SEP has a smaller coverage. It is of interest to verify whether these two measures can promote cooperation and which one is more efficient. Simulate results reveal that both of them can promote cooperation remarkably. Specifically speaking, SLP shows constant advantage from the point of view either of fractions of cooperation or average payoff. PMID- 25137049 TI - The MacBlue binary transgene (csf1r-gal4VP16/UAS-ECFP) provides a novel marker for visualisation of subsets of monocytes, macrophages and dendritic cells and responsiveness to CSF1 administration. AB - The MacBlue transgenic mouse uses the Csf1r promoter and first intron to drive expression of gal4-VP16, which in turn drives a cointegrated gal4-responsive UAS ECFP cassette. The Csf1r promoter region used contains a deletion of a 150 bp conserved region covering trophoblast and osteoclast-specific transcription start sites. In this study, we examined expression of the transgene in embryos and adult mice. In embryos, ECFP was expressed in the large majority of macrophages derived from the yolk sac, and as the liver became a major site of monocytopoiesis. In adults, ECFP was detected at high levels in both Ly6C+ and Ly6C- monocytes and distinguished them from Ly6C+, F4/80+, CSF1R+ immature myeloid cells in peripheral blood. ECFP was also detected in the large majority of microglia and Langerhans cells. However, expression was lost from the majority of tissue macrophages, including Kupffer cells in the liver and F4/80+ macrophages of the lung, kidney, spleen and intestine. The small numbers of positive cells isolated from the liver resembled blood monocytes. In the gut, ECFP+ cells were identified primarily as classical dendritic cells or blood monocytes in disaggregated cell preparations. Immunohistochemistry showed large numbers of ECFP+ cells in the Peyer's patch and isolated lymphoid follicles. The MacBlue transgene was used to investigate the effect of treatment with CSF1-Fc, a form of the growth factor with longer half-life and efficacy. CSF1-Fc massively expanded both the immature myeloid cell (ECFP-) and Ly6C+ monocyte populations, but had a smaller effect on Ly6C- monocytes. There were proportional increases in ECFP+ cells detected in lung and liver, consistent with monocyte infiltration, but no generation of ECFP+ Kupffer cells. In the gut, there was selective infiltration of large numbers of cells into the lamina propria and Peyer's patches. We discuss the use of the MacBlue transgene as a marker of monocyte/macrophage/dendritic cell differentiation. PMID- 25137050 TI - Transcriptional response of Musca domestica larvae to bacterial infection. AB - The house fly Musca domestica, a cosmopolitan dipteran insect, is a significant vector for human and animal bacterial pathogens, but little is known about its immune response to these pathogens. To address this issue, we inoculated the larvae with a mixture of Escherichia coli and Staphylococcus aureus and profiled the transcriptome 6, 24, and 48 h thereafter. Many genes known to controlling innate immunity in insects were induced following infection, including genes encoding pattern recognition proteins (PGRPs), various components of the Toll and IMD signaling pathways and of the proPO-activating and redox systems, and multiple antimicrobial peptides. Interestingly, we also uncovered a large set of novel immune response genes including two broad-spectrum antimicrobial peptides (muscin and domesticin), which might have evolved to adapt to house-fly's unique ecological environments. Finally, genes mediating oxidative phosphorylation were repressed at 48 h post-infection, suggesting disruption of energy homeostasis and mitochondrial function at the late stages of infection. Collectively, our data reveal dynamic changes in gene expression following bacterial infection in the house fly, paving the way for future in-depth analysis of M. domestica's immune system. PMID- 25137052 TI - Doxycycline inducible Kruppel-like factor 4 lentiviral vector mediates mesenchymal to epithelial transition in ovarian cancer cells. AB - Ovarian cancer presents therapeutic challenges due to its typically late detection, aggressive metastasis, and therapeutic resistance. The transcription factor Kruppel-like factor 4 (KLF4) has been implicated in human cancers as a tumor suppressor or oncogene, although its role depends greatly on the cellular context. The role of KLF4 in ovarian cancer has not been elucidated in mechanistic detail. In this study, we investigated the role of KLF4 in ovarian cancer cells by transducing the ovarian cancer cell lines SKOV3 and OVCAR3 with a doxycycline-inducible KLF4 lentiviral vector. Overexpression of KLF4 reduced cell proliferation, migration, and invasion. The epithelial cell marker gene E cadherin was significantly upregulated, whereas the mesenchymal cell marker genes vimentin, twist1 and snail2 (slug) were downregulated in both KLF4-expressing SKOV3 and OVCAR3 cells. KLF4 inhibited the transforming growth factor beta (TGFbeta)-induced epithelial to mesenchymal transition (EMT) in ovarian cancer cells. Taken together, our data demonstrate that KLF4 functions as a tumor suppressor gene in ovarian cancer cells by inhibiting TGFbeta-induced EMT. PMID- 25137053 TI - Refined candidate region for F4ab/ac enterotoxigenic Escherichia coli susceptibility situated proximal to MUC13 in pigs. AB - F4 enterotoxigenic Escherichia coli (F4 ETEC) are an important cause of diarrhea in neonatal and newly-weaned pigs. Based on the predicted differential O glycosylation patterns of the 2 MUC13 variants (MUC13A and MUC13B) in F4ac ETEC susceptible and F4ac ETEC resistant pigs, the MUC13 gene was recently proposed as the causal gene for F4ac ETEC susceptibility. Because the absence of MUC13 on Western blot from brush border membrane vesicles of F4ab/acR+ pigs and the absence of F4ac attachment to immunoprecipitated MUC13 could not support this hypothesis, a new GWAS study was performed using 52 non-adhesive and 68 strong adhesive pigs for F4ab/ac ETEC originating from 5 Belgian farms. A refined candidate region (chr13: 144,810,100-144,993,222) for F4ab/ac ETEC susceptibility was identified with MUC13 adjacent to the distal part of the region. This candidate region lacks annotated genes and contains a sequence gap based on the sequence of the porcine GenomeBuild 10.2. We hypothesize that a porcine orphan gene or trans-acting element present in the identified candidate region has an effect on the glycosylation of F4 binding proteins and therefore determines the F4ab/ac ETEC susceptibility in pigs. PMID- 25137056 TI - ACUTE INTESTINAL OBSTRUCTION DUE TO INTRA-ABDOMINAL CAUSES. PMID- 25137054 TI - Identification, localization, and quantification of neuronal cell membrane receptors with plasmonic probes: role of protein kinase D1 in their distribution. AB - Detecting, imaging, and being able to localize the distribution of several cell membrane receptors on a single neuron are very important topics in neuroscience research. In the present work, the distribution of metabotropic glutamate receptor 1a (mGluR1a) density on neuron cells on subcellular length scales is determined by evaluating the role played by protein kinase D1 (PKD1) in the trafficking of membrane proteins, comparing the distribution of mGluR1a in experiments performed in endogenous PKD1 expression with those in the presence of kinase-inactive protein kinase D1 (PKD1-kd). The localization, distribution, and density of cell surface mGluR1a were evaluated using 90 nm diameter Au nanoparticle (NP) probes specifically functionalized with a high-affinity and multivalent labeling function, which allows not only imaging NPs where this receptor is present but also quantifying by optical means the NP density. This is so because the NP generates a density (rho)-dependent SERS response that facilitated a spatial mapping of the mGluR1a density distribution on subcellular length scales (dendrites and axons) in an optical microscope. The measured rho values were found to be significantly higher on dendrites than on axons for endogenous PKD1, while an increase of rho on axons was observed when PKD1 is altered. The spatial distribution of the NP immunolabels through scanning electron microscopy (SEM) confirmed the results obtained by fluorescence bright field analysis and dark-field spectroscopy and provided additional structural details. In addition, it is shown using electrodynamic simulations that SERS spectroscopy could be a very sensitive tool for the spatial mapping of cell membrane receptors on subcellular length scales, as SERS signals are almost linearly dependent on NP density and therefore give indirect information on the distribution of cell membrane proteins. This result is important since the calibration of the rho-dependent near-field enhancement of the Au immunolabels through correlation of SERS and SEM paves the way toward quantitative immunolabeling studies of cell membrane proteins involved in neuron polarity. From the molecular biology point of view, this study shows that in cultured hippocampal pyramidal cells mGluR1a is predominantly transported to dendrites and excluded from axons. Expression of kinase-inactive protein kinase D1 (PKD1-kd) dramatically and selectively alters the intracellular trafficking and membrane delivery of mGluR1a-containing vesicles. PMID- 25137058 TI - 3D reconstruction of atomic structures from high angle annular dark field (HAADF) STEM images and its application on zeolite silicalite-1. AB - High-resolution transmission electron microscopy (HRTEM) has shown to be very powerful for solving three-dimensional (3D) structures of unknown crystals. HRTEM has a unique advantage over diffraction for solving structures. Crystallographic structure factor phases, which are lost in diffraction can be directly obtained from HRTEM images. For the determination of a 3D crystalline structure by HRTEM, the crystallographic structure factor amplitudes and phases extracted from HRTEM images along different zone axes are combined to reconstruct a 3D electrostatic potential map. In recent years, scanning transmission electron microscopy (STEM) has reached the atomic resolution, which is comparable to that of HRTEM. Here we show, for the first time, that the structure factor phases can be also obtained from high angle annular dark-field (HAADF)-STEM images and used for 3D reconstruction of atomic structures. This is applied to the complex zeolite structure, silicalite-1 (Formula SiO2, framework code MFI, Pnma, a = 20.090 A, b = 19.738 A and c = 13.142 A). We have compared the amplitudes and phases obtained from HAADF-STEM images with those from HRTEM images. PMID- 25137055 TI - Synthesis, PL characterizations and concentration quenching effect in Dy(3+) and Eu(3+) activated LiCaBO3 phosphor. AB - LiCaBO3 :Dy(3+) /Eu(3+) phosphors were synthesized by a solid-state reaction. The synthesized materials were characterized using powder X-ray diffraction pattern (XRD) for confirmation. All the structural parameters were calculated from the XRD data. Scanning electron microscopy (SEM) images showed rod-like morphology. Photoluminescence (PL) emission spectra showed two emissions (484 and 577 nm) in Dy(3+) -doped LiCaBO3 :Dy(3+) phosphors with the concentration quenching effect and the critical distance was calculated to be about 22.76 A. LiCaBO3 :Eu(3+) phosphor was effectively excited by a near-UV light of 392 nm. The emission spectra exhibited the transition from (5) D0 level to (7) FJ (J = 0-2) with main emission at 614 nm, which comes from the electrodipole transition because of the asymmetric point group. The quenching concentration of Eu(3+) is about 0.2 mol%, and the critical distance was calculated to be about 38.93 A. PMID- 25137059 TI - Diabetes mellitus as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. AB - OBJECTIVE: To determine the association between diabetes mellitus (DM) and primary open-angle glaucoma (POAG). METHODS: This is a systematic review and meta analysis of case-control and cohort studies. The literature search included two databases (PubMed and Embase) and the reference lists of the retrieved studies. Separate meta-analyses for case-control studies and cohort studies were conducted using random-effects models, with results reported as adjusted odds ratios (ORs) and relative risks (RRs), respectively. RESULTS: Thirteen studies--seven case control studies and six population-based cohort studies--were included in this meta-analysis. The pooled RR of the association between DM and POAG based on the risk estimates of the six cohort studies was 1.40 (95% CI, 1.25-1.57). The pooled OR of the association between DM and POAG based on the risk estimates of the seven case-control studies was 1.49 (95% CI, 1.17-1.88). There was considerable heterogeneity among the case-control studies that reported an association between DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort studies (P = 0.377). After omitting the case-control study that contributed significantly to the heterogeneity, the pooled OR for the association between DM and POAG was 1.35 (95% CI, 1.06-1.74). CONCLUSIONS: Individuals with DM have an increased risk of developing POAG. PMID- 25137060 TI - Genomic inverse PCR for exploration of ligated breakpoints (GIPFEL), a new method to detect translocations in leukemia. AB - Here we present a novel method "Genomic inverse PCR for exploration of ligated breakpoints" (GIPFEL) that allows the sensitive detection of recurrent chromosomal translocations. This technique utilizes limited amounts of DNA as starting material and relies on PCR based quantification of unique DNA sequences that are created by circular ligation of restricted genomic DNA from translocation bearing cells. Because the complete potential breakpoint region is interrogated, a prior knowledge of the individual, specific interchromosomal fusion site is not required. We validated GIPFEL for the five most common gene fusions associated with childhood leukemia (MLL-AF4, MLL-AF9, MLL-ENL, ETV6 RUNX1, and TCF3-PBX1). A workflow of restriction digest, purification, ligation, removal of linear fragments and precipitation enriching for circular DNA was developed. GIPFEL allowed detection of translocation specific signature sequences down to a 10-4 dilution which is close to the theoretical limit. In a blinded proof-of-principle study utilizing DNA from cell lines and 144 children with B precursor-ALL associated translocations this method was 100% specific with no false positive results. Sensitivity was 83%, 65%, and 24% for t(4;11), t(9;11) and t(11;19) respectively. Translocation t(12;21) was correctly detected in 64% and t(1;19) in 39% of the cases. In contrast to other methods, the characteristics of GIPFEL make it particularly attractive for prospective studies. PMID- 25137061 TI - A national survey of skin infections, care behaviors and MRSA knowledge in the United States. AB - A nationally representative sample of approximately 2000 individuals was surveyed to assess SSTI infections over their lifetime and then prospectively over six months. Knowledge of MRSA, future likelihood to self-treat a SSTI and self-care behaviors was also queried. Chi square tests, linear and multinomial regression were used for analysis. About 50% of those with a reported history of a SSTI typical of MRSA had sought medical treatment. MRSA knowledge was low: 28% of respondents could describe MRSA. Use of protective self-care behaviors that may reduce transmission, such as covering a lesion, differed with knowledge of MRSA and socio-demographics. Those reporting a history of a MRSA-like SSTI were more likely to respond that they would self-treat than those without such a history (OR 2.05 95% CI 1.40, 3.01; p<0.001). Since half of respondents reported not seeking care for past lesions, incidence determined from clinical encounters would greatly underestimate true incidence. MRSA knowledge was not associated with seeking medical care, but was associated with self-care practices that may decrease transmission. PMID- 25137062 TI - The IkappaB kinase complex is required for plexin-B-mediated activation of RhoA. AB - Plexins are widely expressed transmembrane proteins that mediate the cellular effects of semaphorins. The molecular mechanisms of plexin-mediated signal transduction are still poorly understood. Here we show that signalling via B family plexins leading to the activation of the small GTPase RhoA requires activation of the IkappaB kinase (IKK)-complex. In contrast, plexin-B-dependent regulation of R-Ras activity is not affected by IKK activity. This regulation of plexin signalling depends on the kinase activity of the IKK-complex, but is independent of NF-kappaB activation. We confirm that the IKK-complex is active in tumour cells and osteoblasts, and we demonstrate that plexin-B-dependent tumour cell invasiveness and regulation of osteoblast differentiation require an active IKK-complex. This study identifies a novel, NF-kappaB-independent function of the IKK-complex and shows that IKK directs plexin-B signalling to the activation of RhoA. PMID- 25137064 TI - Conscious brain-to-brain communication in humans using non-invasive technologies. AB - Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues. PMID- 25137065 TI - Pyramidal cells make specific connections onto smooth (GABAergic) neurons in mouse visual cortex. AB - One of the hallmarks of neocortical circuits is the predominance of recurrent excitation between pyramidal neurons, which is balanced by recurrent inhibition from smooth GABAergic neurons. It has been previously described that in layer 2/3 of primary visual cortex (V1) of cat and monkey, pyramidal cells filled with horseradish peroxidase connect approximately in proportion to the spiny (excitatory, 95% and 81%, respectively) and smooth (GABAergic, 5% and 19%, respectively) dendrites found in the neuropil. By contrast, a recent ultrastructural study of V1 in a single mouse found that smooth neurons formed 51% of the targets of the superficial layer pyramidal cells. This suggests that either the neuropil of this particular mouse V1 had a dramatically different composition to that of V1 in cat and monkey, or that smooth neurons were specifically targeted by the pyramidal cells in that mouse. We tested these hypotheses by examining similar cells filled with biocytin in a sample of five mice. We found that the average composition of the neuropil in V1 of these mice was similar to that described for cat and monkey V1, but that the superficial layer pyramidal cells do form proportionately more synapses with smooth dendrites than the equivalent neurons in cat or monkey. These distributions may underlie the distinct differences in functional architecture of V1 between rodent and higher mammals. PMID- 25137066 TI - Digital mapping of soil organic carbon contents and stocks in Denmark. AB - Estimation of carbon contents and stocks are important for carbon sequestration, greenhouse gas emissions and national carbon balance inventories. For Denmark, we modeled the vertical distribution of soil organic carbon (SOC) and bulk density, and mapped its spatial distribution at five standard soil depth intervals (0-5, 5 15, 15-30, 30-60 and 60-100 cm) using 18 environmental variables as predictors. SOC distribution was influenced by precipitation, land use, soil type, wetland, elevation, wetness index, and multi-resolution index of valley bottom flatness. The highest average SOC content of 20 g kg(-1) was reported for 0-5 cm soil, whereas there was on average 2.2 g SOC kg(-1) at 60-100 cm depth. For SOC and bulk density prediction precision decreased with soil depth, and a standard error of 2.8 g kg(-1) was found at 60-100 cm soil depth. Average SOC stock for 0-30 cm was 72 t ha(-1) and in the top 1 m there was 120 t SOC ha(-1). In total, the soils stored approximately 570 Tg C within the top 1 m. The soils under agriculture had the highest amount of carbon (444 Tg) followed by forest and semi natural vegetation that contributed 11% of the total SOC stock. More than 60% of the total SOC stock was present in Podzols and Luvisols. Compared to previous estimates, our approach is more reliable as we adopted a robust quantification technique and mapped the spatial distribution of SOC stock and prediction uncertainty. The estimation was validated using common statistical indices and the data and high-resolution maps could be used for future soil carbon assessment and inventories. PMID- 25137068 TI - Nitrogen-enriched hierarchically porous carbons prepared from polybenzoxazine for high-performance supercapacitors. AB - Nitrogen-enriched hierarchically porous carbons (HPCs) were synthesized from a novel nitrile-functionalized benzoxazine based on benzoxazine chemistry using a soft-templating method and a potassium hydroxide (KOH) chemical activation method and used as electrode materials for supercapacitors. The textural and chemical properties could be easily tuned by adding a soft template and changing the activation temperature. The introduction of the soft-templating agent (surfactant F127) resulted in the formation of mesopores, which facilitated fast ionic diffusion and reduced the internal resistance. The micropores of HPCs were extensively developed by KOH activation to provide large electrochemical double layer capacitance. As the activation temperature increased from 600 to 800 degrees C, the specific surface area of nitrogen-enriched carbons increased dramatically, micropores were enlarged, and more meso/macropores were developed, but the nitrogen and oxygen content decreased, which affected the electrochemical performance. The sample HPC-800 activated at 800 degrees C possesses a high specific surface area (1555.4 m(2) g(-1)), high oxygen (10.61 wt %) and nitrogen (3.64 wt %) contents, a hierarchical pore structure, a high graphitization degree, and good electrical conductivity. It shows great pseudocapacitance and the largest specific capacitance of 641.6 F g(-1) at a current density of 1 A g( 1) in a 6 mol L(-1) KOH aqueous electrolyte when measured in a three-electrode system. Furthermore, the HPC-800 electrode exhibits excellent rate capability (443.0 F g(-1) remained at 40 A g(-1)) and good cycling stability (94.3% capacitance retention over 5000 cycles). PMID- 25137067 TI - Efficient in vivo deletion of a large imprinted lncRNA by CRISPR/Cas9. AB - Recent genome-wide studies have revealed that the majority of the mouse genome is transcribed as non-coding RNAs (ncRNAs) and growing evidence supports the importance of ncRNAs in regulating gene expression and epigenetic processes. However, the low efficiency of conventional gene targeting strategies has hindered the functional study of ncRNAs in vivo, particularly in generating large fragment deletions of long non-coding RNAs (lncRNAs) with multiple expression variants. The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system has recently been applied as an efficient tool for engineering site-specific mutations of protein-coding genes in the genome. In this study, we explored the potential of using the CRISPR/Cas9 system to generate large genomic deletions of lncRNAs in mice. We developed an efficient one-step strategy to target the maternally expressed lncRNA, Rian, on chromosome 12 in mice. We showed that paired sgRNAs can precisely generate large deletions up to 23kb and the deletion efficiency can be further improved up to 33% by combining multiple sgRNAs. The deletion successfully abolished the expression of Rian from the maternally inherited allele, validating the biological relevance of the mutations in studying an imprinted locus. Mutation of Rian has differential effects on expression of nearby genes in different somatic tissues. Taken together, we have established a robust one-step method to engineer large deletions to knockout lncRNA genes with the CRISPR/Cas9 system. Our work will facilitate future functional studies of other lncRNAs in vivo. PMID- 25137063 TI - Toxicological profile of ultrapure 2,2',3,4,4',5,5'-heptachlorbiphenyl (PCB 180) in adult rats. AB - PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions. PMID- 25137069 TI - Hope for the best or prepare for the worst? Towards a spatial cognitive bias test for mice. AB - Cognitive bias, the altered information processing resulting from the background emotional state of an individual, has been suggested as a promising new indicator of animal emotion. Comparable to anxious or depressed humans, animals in a putatively negative emotional state are more likely to judge an ambiguous stimulus as if it predicts a negative event, than those in positive states. The present study aimed to establish a cognitive bias test for mice based on a spatial judgment task and to apply it in a pilot study to serotonin transporter (5-HTT) knockout mice, a well-established mouse model for the study of anxiety- and depression-related behavior. In a first step, we validated that our setup can assess different expectations about the outcome of an ambiguous stimulus: mice having learned to expect something positive within a maze differed significantly in their behavior towards an unfamiliar location than animals having learned to expect something negative. In a second step, the use of spatial location as a discriminatory stimulus was confirmed by showing that mice interpret an ambiguous stimulus depending on its spatial location, with a position exactly midway between a positive and a negative reference point provoking the highest level of ambiguity. Finally, the anxiety- and depression-like phenotype of the 5-HTT knockout mouse model manifested--comparable to human conditions--in a trend for a negatively distorted interpretation of ambiguous information, albeit this effect was not statistically significant. The results suggest that the present cognitive bias test provides a useful basis to study the emotional state in mice, which may not only increase the translational value of animal models in the study of human affective disorders, but which is also a central objective of animal welfare research. PMID- 25137070 TI - Catalytic profile of Arabidopsis peroxidases, AtPrx-2, 25 and 71, contributing to stem lignification. AB - Lignins are aromatic heteropolymers that arise from oxidative coupling of lignin precursors, including lignin monomers (p-coumaryl, coniferyl, and sinapyl alcohols), oligomers, and polymers. Whereas plant peroxidases have been shown to catalyze oxidative coupling of monolignols, the oxidation activity of well studied plant peroxidases, such as horseradish peroxidase C (HRP-C) and AtPrx53, are quite low for sinapyl alcohol. This characteristic difference has led to controversy regarding the oxidation mechanism of sinapyl alcohol and lignin oligomers and polymers by plant peroxidases. The present study explored the oxidation activities of three plant peroxidases, AtPrx2, AtPrx25, and AtPrx71, which have been already shown to be involved in lignification in the Arabidopsis stem. Recombinant proteins of these peroxidases (rAtPrxs) were produced in Escherichia coli as inclusion bodies and successfully refolded to yield their active forms. rAtPrx2, rAtPrx25, and rAtPrx71 were found to oxidize two syringyl compounds (2,6-dimethoxyphenol and syringaldazine), which were employed here as model monolignol compounds, with higher specific activities than HRP-C and rAtPrx53. Interestingly, rAtPrx2 and rAtPrx71 oxidized syringyl compounds more efficiently than guaiacol. Moreover, assays with ferrocytochrome c as a substrate showed that AtPrx2, AtPrx25, and AtPrx71 possessed the ability to oxidize large molecules. This characteristic may originate in a protein radical. These results suggest that the plant peroxidases responsible for lignin polymerization are able to directly oxidize all lignin precursors. PMID- 25137071 TI - Circulating miR-19a and miR-205 in serum may predict the sensitivity of luminal A subtype of breast cancer patients to neoadjuvant chemotherapy with epirubicin plus paclitaxel. AB - BACKGROUND: The luminal A subtype of breast cancer has a good prognosis and is sensitive to endocrine therapy but is less sensitive to chemotherapy. It is necessary to identify biomarkers to predict chemosensitivity and avoid over treatment. We hypothesized that miRNAs in the serum might be associated with chemosensitivity. METHODS: Sixty-eight breast cancer patients received neoadjuvant chemotherapy with epirubicin plus paclitaxel. The serum of the patients was collected before chemotherapy and stored at -80 degrees C. The samples were classified into two groups in term of the chemosensitivity. We identified the differential expression patterns of miRNAs between the chemotherapy sensitive and resistant groups using microRNA profiling. Four miRNAs that were differentially expressed between the two groups were further validated in another 56 samples. We created a model fitting formula and a receiver operating characteristics (ROC) curve using logistic regression analysis to evaluate the prediction potency. RESULTS: We identified 8 miRNAs differentially expressed between the two groups: 6 miRNAs were up-regulated, and 2 miRNAs were down-regulated in the resistant group compared with the sensitive group. The expression of miR-19a and miR-205 were determined to have significant differences between the two groups (P<0.05). A predictive model of these two miRNAs was created by the logistic regression analysis. The probability of this model was 89.71%. Based on the ROC curve, the specificity was 75.00%, and the sensitivity was 81.25%. CONCLUSIONS: The combination of miR-19a and miR-205 in the serum may predict the chemosensitivity of luminal A subtype of breast cancer to epirubicin plus paclitaxel neoadjuvant chemotherapy. PMID- 25137072 TI - The free caesareans policy in low-income settings: an interrupted time series analysis in Mali (2003-2012). AB - INTRODUCTION: Several countries have instituted fee exemptions for caesareans to reduce maternal and newborn mortality. OBJECTIVES: To evaluate the effect of fee exemptions for caesareans on population caesarean rates taking into account different levels of accessibility. METHODS: The observation period was from January 2003 to May 2012 in one Region and covered 11.7 million person-years. Exemption fees for caesareans were adopted on June 26, 2005. Data were obtained from a registration system implemented in 2003 that tracks all obstetrical emergencies and interventions including caesareans. The pre-intervention period was 30 months and the post-intervention period was 83 months. We used an interrupted time series to evaluate the trend before and after the policy adoption and the overall tendency. FINDINGS: During the study period, the caesarean rate increased from 0.25 to 1.5% for the entire population. For women living in cities with district hospitals that provided caesareans, the rate increased from 1.7% before the policy was enforced to 5.7% 83 months later. No significant change in trends was observed among women living in villages with a healthcare centre or those in villages with no healthcare facility. For the latter, the caesarean rate increased from 0.4 to 1%. CONCLUSIONS: After nine years of implementation policy in Mali, the caesarean rate achieved in cities with a district hospital reached the full beneficial effect of this measure, whereas for women living elsewhere this policy did not increase the caesarean rate to a level that could contribute effectively to reduce their risk of maternal death. Only universal access to this essential intervention could reduce the inequities and increase the effectiveness of this policy. PMID- 25137073 TI - pH dependence of conformational fluctuations of the protein backbone. AB - Proton binding equilibria (pK(a) values) of ionizable groups in proteins are exquisitely sensitive to their microenvironments. Apparent pK(a) values measured for individual ionizable residues with NMR spectroscopy are actually population weighted averages of the pK(a) in different conformational microstates. NMR spectroscopy experiments with staphylococcal nuclease were used to test the hypothesis that pK(a) values of surface Glu and Asp residues are affected by pH sensitive fluctuations of the backbone between folded and locally unfolded conformations. (15)N spin relaxation studies showed that as the pH decreases from the neutral into the acidic range the amplitudes of backbone fluctuations in the ps-ns timescale increase near carboxylic residues. Hydrogen exchange experiments suggested that backbone conformational fluctuations promoted by decreasing pH also reflect slower local or sub-global unfolding near carboxylic groups. This study has implications for structure-based pKa calculations: (1) The timescale of the backbone's response to ionization events in proteins can range from ps to ms, and even longer; (2) pH-sensitive fluctuations of the backbone can be localized to both the segment the ionizable residue is attached to or the one that occludes the ionizable group; (3) Structural perturbations are not necessarily propagated through Coulomb interactions; instead, local fluctuations appear to be coupled through the co-operativity inherent to elements of secondary structure and to networks of hydrogen bonds. These results are consistent with the idea that local conformational fluctuations and stabilities are important determinants of apparent pK(a) values of ionizable residues in proteins. PMID- 25137075 TI - Obstetric triage. PMID- 25137074 TI - Orthology detection combining clustering and synteny for very large datasets. AB - The elucidation of orthology relationships is an important step both in gene function prediction as well as towards understanding patterns of sequence evolution. Orthology assignments are usually derived directly from sequence similarities for large data because more exact approaches exhibit too high computational costs. Here we present PoFF, an extension for the standalone tool Proteinortho, which enhances orthology detection by combining clustering, sequence similarity, and synteny. In the course of this work, FFAdj-MCS, a heuristic that assesses pairwise gene order using adjacencies (a similarity measure related to the breakpoint distance) was adapted to support multiple linear chromosomes and extended to detect duplicated regions. PoFF largely reduces the number of false positives and enables more fine-grained predictions than purely similarity-based approaches. The extension maintains the low memory requirements and the efficient concurrency options of its basis Proteinortho, making the software applicable to very large datasets. PMID- 25137076 TI - Should informed consent be required for routine newborn screening and for the storage of blood samples? PMID- 25137079 TI - Subsequent pregnancy after having a baby who was hospitalized in the NICU. AB - PURPOSE: To understand experiences of mothers who had a baby hospitalized in the NICU and then decided to have another pregnancy. STUDY DESIGN AND METHODS: We used a descriptive phenomenological approach to study 12 mothers in Japan who had a child hospitalized in the NICU and had a subsequent child. Data were collected by semistructured interviews that occurred two to four times per participant. Data were analyzed using Colaizzi's method. RESULTS: Although all of the mothers had a child who was making steady progress, they experienced difficulty when deciding on having another pregnancy. Our analysis identified five theme clusters: delaying pregnancy; unwavering view about having subsequent children; changing values regarding pregnancy and childbirth; relief of anxiety and fear about repeated hospitalization in the NICU; and preparedness to accept the outcome of pregnancy. CLINICAL IMPLICATIONS: Our study suggests that mothers require support during babies' hospitalization in the NICU and for the process of decision-making about a subsequent pregnancy. Family-centered care as the basis for nursing practice in the NICU is ideal to provide this type of support. PMID- 25137078 TI - Women's perspectives on falls and fall prevention during pregnancy. AB - BACKGROUND: Falls are the leading cause of unintentional injury in women. During pregnancy, even a minor fall can result in adverse consequences. Evidence to inform effective and developmentally appropriate pregnancy fall prevention programs is lacking. Early research on pregnancy fall prevention suggests that exercise may reduce falls. However, acceptability and effectiveness of pregnancy fall prevention programs are untested. PURPOSE: To better understand postpartum women's perspective and preferences on fall prevention strategies during pregnancy to formulate an intervention. METHODS: Focus groups and individual interviews were conducted with 31 postpartum women using descriptive qualitative methodology. Discussion of falls during pregnancy and fall prevention strategies was guided by a focus group protocol and enhanced by 1- to 3-minute videos on proposed interventions. Focus groups were audio recorded, transcribed, and analyzed using NVivo 10 software. RESULTS: Emerging themes were environmental circumstances and physical changes of pregnancy leading to a fall, prevention strategies, barriers, safety concerns, and marketing a fall prevention program. Wet surfaces and inappropriate footwear commonly contributed to falls. Women preferred direct provider counseling and programs including yoga and Pilates. IMPLICATIONS: Fall prevention strategies tailored to pregnant women are needed. Perspectives of postpartum women support fall prevention through provider counseling and individual or supervised exercise programs. PMID- 25137080 TI - Breast cancer risk assessment in primary care. AB - Breast cancer is the most common cancer (when excluding skin cancers) in women and the second most common cause of cancer death in women, with a lifetime prevalence of 12.5% (, ; ). Breast cancer screening reduces risk of cancer death, thereby increasing rate of survival to up to 89% for women with stage 1 and 2 breast cancer (; ). Despite these data, undue harm may occur with unnecessary screening because overidentification of risk, and excessive, costly biopsies may result. Costs and benefits of screening must be weighed. Nurses at all levels can play a pivotal role in promotion of appropriate breast cancer screening and subsequently breast cancer prevention by using accurate screening tools, such as the Tyrer-Cuzick model. Although there are some limitations with this tool, screening at the primary care level has demonstrated improved clinical outcomes (). Its use can help nurses accurately assess a woman's breast cancer risk, by promoting appropriate screening at the primary care level (). PMID- 25137081 TI - Parenting and concerns of pregnant women in buprenorphine treatment. AB - PURPOSE: Opioid-dependent pregnant women are characterized by drug use during pregnancy and deficits in knowledge of newborn care and feeding, and of child development. We assessed parenting skills and concerns among pregnant women in buprenorphine treatment for prescription opioid dependence. STUDY DESIGN AND METHODS: We interviewed 32 pregnant women who received buprenorphine treatment for prescription opioid dependence in a primary care setting and administered questionnaires, including the Adult-Adolescent Parenting Inventory version 2 (AAPI-2) and Childhood Experience of Care and Abuse Questionnaire. RESULTS: AAPI 2 scores revealed medium risk of abuse for all five scales: inappropriate expectations of the child, low level of empathy, strong belief in corporal punishment, reversal of parent-child roles, and oppression of children's power and independence. Primary concerns of participants were neonatal abstinence syndrome (NAS) and their child's health. Pregnant women who received buprenorphine for treatment of prescription opioid dependence showed a lack of appropriate parenting skills, but did not express concern about their ability to parent. CLINICAL IMPLICATIONS: Our findings suggest a need for nurses to assist prescription opioid-dependent pregnant women in acquiring additional parenting skills, to refer for educational parenting intervention, and to educate patients about NAS. PMID- 25137083 TI - Potential tools to assess diet quality. PMID- 25137082 TI - Women's experience of decision-making with medication abortion. AB - BACKGROUND: Medication abortion received regulatory approval in 2001 in the United States with healthcare providers increasingly offering this method. However, most studies in the United States have only explored acceptability and decision-making with women who participated in clinical trials. Overall, the literature on women's experience with a method that it is now widely available is under research in the United States. OBJECTIVE: To describe and analyze the women's experience as they choose the option of and experienced the process of medication abortion. DESIGN: A constructivist grounded theory study. SETTING: Outpatient clinical offices in a three-state area in the northeast region of the United States. PARTICIPANTS: A purposive sample of 22 women aged 16 to 45 who experienced a medication abortion. METHODS: Data were collected by in-depth, open ended, face-to-face interviews. The constant comparative method was used for analysis. RESULTS: Five interwoven categories emerged regarding women's initial decision to have a medication abortion: choosing a natural process, avoiding "surgery," respecting the "baby," scheduling to meet needs, and appreciating the home setting. The enhanced sense of personal control associated with the medication abortion option was the overriding reason given for choosing this method. CONCLUSION: This study contributes to the paucity of literature on the reasons why women choose medication abortion. It is important for nurses to understand the complexity of medication abortion decision-making so that they can effectively support women through this process. PMID- 25137084 TI - Human factors, usability, and the electronic health record. PMID- 25137085 TI - Fostering hope: documenting interventions targeting Ethiopian child brides. PMID- 25137087 TI - Underwater birth: an elective intervention with safety concerns. PMID- 25137088 TI - Synthesis of sulfur-bridged polycycles via Pd-catalyzed dehydrogenative cyclization. AB - A general approach to sulfur-bridged polycycles by palladium-catalyzed double C(sp(2))-H bond oxidative cyclization is presented. This protocol afforded diverse sulfur-bridged five-, six-, and seven-membered polycycles in moderate to good yields with a tolerance for a wide variety of functional groups. A sulfide bridged six-membered pyrene-thienoacene compound was synthesized readily using this method, and excellent performance for photoluminescence quantum yield was observed. PMID- 25137089 TI - Quantitative measurement of ligand exchange on iron oxides via radiolabeled oleic acid. AB - Ligand exchange of hydrophilic molecules on the surface of hydrophobic iron oxide nanoparticles produced via thermal decomposition of chelated iron precursors is a common method for producing aqueous suspensions of particles for biomedical applications. Despite the wide use, relatively little is understood about the efficiency of ligand exchange on the surface of iron oxide nanoparticles and how much of the hydrophobic ligand is removed. To address this issue, we utilized a radiotracer technique to track the exchange of a radiolabeled (14)C-oleic acid ligand with hydrophilic ligands on the surface of magnetite nanoparticles. Iron oxide nanoparticles functionalized with (14)C-oleic acid were modified with poly(ethylene glycol) with terminal functional groups including, L-3,4 dihydroxyphenylalanine, a nitrated L-3,4-dihydroxyphenylalanine, carboxylic acid, a phosphonate, and an amine. Following ligand exchange, the nanoparticles and byproducts were analyzed using liquid scintillation counting and inductively coupled plasma mass spectroscopy. The labeled and unlabeled particles were further characterized by transmission electron microscopy and dynamic light scattering to determine particle size, hydrodynamic diameter, and zeta potential. The unlabeled particles were characterized via thermogravimetric analysis and vibrating sample magnetometry. Radioanalytical determination of the (14)C from (14)C-oleic acid was used to calculate the amount of oleic acid remaining on the surface of the particles after purification and ligand exchange. There was a significant loss of oleic acid on the surface of the particles after ligand exchange with amounts varying for the different functional binding groups on the poly(ethylene glycol). Nonetheless, all samples demonstrated some residual oleic acid associated with the particles. Quantification of the oleic acid remaining after ligand exchange reveals a binding hierarchy in which catechol derived anchor groups displace oleic acid on the surface of the nanoparticles better than the phosphonate, followed by the amine and carboxylic acid groups. Furthermore, the results show that these ligand exchange reactions do not necessarily occur to completion as is often assumed, thus leaving a residual amount of oleic acid on the surface of the particles. A thorough analysis of ligand exchange is required to develop nanoparticles that are suitable for their desired application. PMID- 25137091 TI - International nursing partnerships for global cancer control. PMID- 25137090 TI - The effect of temperature on the catalytic conversion of Kraft lignin using near critical water. AB - The catalytic conversion of suspended LignoBoost Kraft lignin was performed in near-critical water using ZrO2/K2CO3 as the catalytic system and phenol as the co solvent and char suppressing agent. The reaction temperature was varied from 290 to 370 degrees C and its effect on the process was investigated in a continuous flow (1kg/h). The yields of water-soluble organics (WSO), bio-oil and char (dry lignin basis) were in the ranges of 5-11%, 69-87% and 16-22%, respectively. The bio-oil, being partially deoxygenated, exhibited higher carbon content and heat value, but lower sulphur content than lignin. The main 1-ring aromatics (in WSO and diethylether-soluble bio-oil) were anisoles, alkylphenols, catechols and guaiacols. The results show that increasing temperature increases the yield of 1 ring aromatics remarkably, while it increases the formation of char moderately. An increase in the yields of anisoles, alkylphenols and catechols, together with a decrease in the yield of guaiacols, was also observed. PMID- 25137093 TI - Cancer in the aging: what are we doing to family caregivers? PMID- 25137092 TI - End-of-life care pathways for improving outcomes in caring for the dying. PMID- 25137094 TI - Panning for the gold in health research: incorporating studies' methodological quality in meta-analysis. AB - BACKGROUND: Systematic reviews now routinely assess methodological quality to gauge the validity of the included studies and of the synthesis as a whole. Although trends from higher quality studies should be clearer, it is uncertain how often meta-analyses incorporate methodological quality in models of study results either as predictors, or, more interestingly, in interactions with theoretical moderators. OBJECTIVE AND METHODS: We survey 200 meta-analyses in three health promotion domains to examine when and how meta-analyses incorporate methodological quality. RESULTS: Although methodological quality assessments commonly appear in contemporary meta-analyses (usually as scales), they are rarely incorporated in analyses, and still more rarely analysed in interaction with theoretical determinants of the success of health promotions. The few meta analyses (2.5%) that did include such an interaction analysis showed that moderator results remained significant in higher quality studies or were present only among higher quality studies. We describe how to model quality interactively with theoretically derived moderators and discuss strengths and weaknesses of this approach and in relation to current meta-analytic practice. CONCLUSIONS: In large literatures exhibiting heterogeneous effects, meta-analyses can incorporate methodological quality and generate conclusions that enable greater confidence not only about the substantive phenomenon but also about the role that methodological quality itself plays. PMID- 25137095 TI - High proton conduction at above 100 degrees C mediated by hydrogen bonding in a lanthanide metal-organic framework. AB - A lanthanide metal-organic framework (MOF) compound of the formulation [Eu2(CO3)(ox)2(H2O)2].4H2O (1, ox = oxalate) was prepared by hydrothermal synthesis with its structure determined crystallographically. Temperature dependent but humidity-independent high proton conduction was observed with a maximum of 2.08 * 10(-3) S cm(-1) achieved at 150 degrees C, well above the normal boiling point of water. Results from detailed structural analyses, comparative measurements of conductivities using regular and deuterated samples, anisotropic conductivity measurements using a single-crystal sample, and variable temperature photoluminescence studies collectively establish that the protons furnished by the Eu(III)-bound and activated aqua ligands are the charge carriers and that the transport of proton is mediated along the crystallographic a-axis by ordered hydrogen-bonded arrays involving both aqua ligands and adjacent oxalate groups in the channels of the open framework. Proton conduction was enhanced with the increase of temperature from room temperature to about 150 degrees C, which can be rationalized in terms of thermal activation of the aqua ligands and the facilitated transport between aqua and adjacent oxalate ligands. A complete thermal loss of the aqua ligands occurred at about 160 degrees C, resulting in the disintegration of the hydrogen-bonded pathway for proton transport and a precipitous drop in conductivity. However, the structural integrity of the MOF was maintained up to 350 degrees C, and upon rehydration, the original structure with the hydrogen-bonded arrays was restored, and so was its high proton conduction ability. PMID- 25137097 TI - The geographic origin of Helicobacter pylori isolated from Costa Rican patients. AB - Helicobacter pylori infects a significant proportion of the world population and it is associated with pathologies which include chronic atrophic gastritis, peptic ulcer, and gastric neoplasias such as gastric adenocarcinoma and MALT lymphoma. Costa Rica has a high prevalence of the infection and an elevated incidence of gastric cancer and its associated mortality. The global population structure for H. pylori has been established using a MLST scheme. The population structure of the strains of H. pylori circulating in Costa Rica is currently unknown. We characterized the geographical origin of 24 H. pylori isolates from Costa Rican patients. We identified 142 new alleles for the genes included in the scheme and in eight of the 24 isolates from Costa Rican patients, all seven alleles sequenced were described for the first time. Twenty-one isolates from Costa Rican patients group with hpEurope strains and the remaining three isolates grouped with hspWAfrica isolates (Bayesian posterior probability values above 0.70, P = 0.05, after 2 000 000 generations). The obtained result in the MLST analysis was not unexpected and reflects the genetic composition of the Costa Rican population. PMID- 25137098 TI - Tax fraud. PMID- 25137099 TI - Hiring scribes. PMID- 25137096 TI - Virulence and draft genome sequence overview of multiple strains of the swine pathogen Haemophilus parasuis. AB - Haemophilus parasuis is the cause of Glasser's disease in swine, which is characterized by systemic infection resulting in polyserositis, meningitis, and arthritis. Investigation of this animal disease is complicated by the enormous differences in the severity of disease caused by H. parasuis strains, ranging from lethal systemic disease to subclinical carriage. To identify differences in genotype that could account for virulence phenotypes, we established the virulence of, and performed whole genome sequence analysis on, 11 H. parasuis strains. Virulence was assessed by evaluating morbidity and mortality following intranasal challenge of Caesarean-derived, colostrum-deprived (CDCD) pigs. Genomic DNA from strains Nagasaki (serotype 5), 12939 (serotype 1), SW140 (serotype 2), 29755 (serotype 5), MN-H (serotype 13), 84-15995 (serotype 15), SW114 (serotype 3), H465 (serotype 11), D74 (serotype 9), and 174 (serotype 7) was used to generate Illumina paired-end libraries for genomic sequencing and de novo assembly. H. parasuis strains Nagasaki, 12939, SH0165 (serotype 5), SW140, 29755, and MN-H exhibited a high level of virulence. Despite minor differences in expression of disease among these groups, all pigs challenged with these strains developed clinical signs consistent with Glasser's disease between 1-7 days post challenge. H. parasuis strains 84-15995 and SW114 were moderately virulent, in that approximately half of the pigs infected with each developed Glasser's disease. H. parasuis strains H465, D74, and 174 were minimally virulent or avirulent in the CDCD pig model. Comparative genomic analysis among strains identified several noteworthy differences in coding regions. These coding regions include predicted outer membrane, metabolism, and pilin or adhesin related genes, some of which likely contributed to the differences in virulence and systemic disease observed following challenge. These data will be useful for identifying H. parasuis virulence factors and vaccine targets. PMID- 25137100 TI - Seeking simplicity. PMID- 25137101 TI - Protecting the family. PMID- 25137102 TI - Leading the charge. PMID- 25137103 TI - Casting a vision. PMID- 25137104 TI - Public mental health. PMID- 25137105 TI - Social determinants of mental health. AB - A person's mental health and many common mental disorders are shaped by various social, economic, and physical environments operating at different stages of life. Risk factors for many common mental disorders are heavily associated with social inequalities, whereby the greater the inequality the higher the inequality in risk. The poor and disadvantaged suffer disproportionately, but those in the middle of the social gradient are also affected. It is of major importance that action is taken to improve the conditions of everyday life, beginning before birth and progressing into early childhood, older childhood and adolescence, during family building and working ages, and through to older age. Action throughout these life stages would provide opportunities for both improving population mental health, and for reducing risk of those mental disorders that are associated with social inequalities. As mental disorders are fundamentally linked to a number of other physical health conditions, these actions would also reduce inequalities in physical health and improve health overall. Action needs to be universal: across the whole of society and proportionate to need. Policy making at all levels of governance and across sectors can make a positive difference. PMID- 25137106 TI - Mental disability, human rights and the capabilities approach: searching for the foundations. AB - Those seeking to improve the well-being of individuals with disabilities worldwide often draw on the idea of human rights. More recently, a variety of international human rights legislation such as the Convention on the Rights of Persons with Disabilities (CRPD) has come into force worldwide. The present article aims to ground human rights of people with disabilities such as those in the CRPD in a theory of social justice called the capabilities approach (CA). This article discusses the reasons for grounding rights in a theory of justice, the links between the CA and human rights, the central concern for disability and individuals with disabilities in the CA, and seven central components of the CA. PMID- 25137107 TI - Climate change: the next challenge for public mental health? AB - Climate change is increasingly recognized as one of the greatest threats to human health of the 21st century, with consequences that mental health professionals are also likely to face. While physical health impacts have been increasingly emphasized in literature and practice, recent scholarly literature indicates that climate change and related weather events and environmental changes can profoundly impact psychological well-being and mental health through both direct and indirect pathways, particularly among those with pre-existing vulnerabilities or those living in ecologically sensitive areas. Although knowledge is still limited about the connections between climate change and mental health, evidence is indicating that impacts may be felt at both the individual and community levels, with mental health outcomes ranging from psychological distress, depression and anxiety, to increased addictions and suicide rates. Drawing on examples from diverse geographical areas, this article highlights some climate sensitive impacts that may be encountered by mental health professionals. We then suggest potential avenues for public mental health in light of current and projected changes, in order to stimulate thought, debate, and action. PMID- 25137108 TI - Evaluation of a comedy intervention to improve coping and help-seeking for mental health problems in a women's prison. AB - Rates of mental illness and self-harm are very high among women prisoners. Questionnaires assessed prisoners' knowledge of and attitudes towards mental health problems, and relevant behavioural intentions before and after the intervention, to evaluate the effectiveness of a comedy show in a women's prison to reduce mental health stigma and improve coping and help-seeking for mental health problems. The intervention appeared to have been successful in improving some aspects of prisoners' knowledge about the effectiveness of psychotherapy (Z = - 2.304, p = 0.021) and likelihood of recovery from mental health problems (Z = - 2.699, p = 0.007). There were significant post-intervention increases in the proportion who stated they would discuss or disclose mental health problems with all but one of the sources of help in the questionnaire, which was consistent with the increases in the number of prisoners who rated themselves as likely to start using different sources of help or prison activities. There was no improvement in intentions to associate with people with a mental health problem. The intervention appeared effective in improving factors that might increase help seeking and improve coping, but not those that would change behaviour towards others with a mental health problem. PMID- 25137109 TI - Disclosure of domestic violence in mental health settings: a qualitative meta synthesis. AB - Little is known about how psychiatric services respond to service users' experiences of domestic violence. This qualitative meta-synthesis examined the healthcare experiences and expectations of mental health service users experiencing domestic violence. Twenty-two biomedical, social science, grey literature databases and websites were searched, supplemented by citation tracking and expert recommendations. Qualitative studies which included mental health service users (aged >= 16 years) with experiences of domestic violence were eligible for inclusion. Two reviewers independently extracted data from included papers and assessed quality. Findings from primary studies were combined using meta-synthesis techniques. Twelve studies provided data on 140 female and four male mental health service users. Themes were generally consistent across studies. Overarching theoretical constructs included the role of professionals in identifying domestic violence and facilitating disclosures, implementing personalized care and referring appropriately. Mental health services often failed to identify and facilitate disclosures of domestic violence, and to develop responses that prioritized service users' safety. Mental health services were reported to give little consideration to the role of domestic violence in precipitating or exacerbating mental illness and the dominance of the biomedical model and stigma of mental illness were found to inhibit effective responses. Mental health services often fail to adequately address the violence experienced by mental health service users. This meta-synthesis highlights the need for mental health services to establish appropriate strategies and responses to domestic violence to ensure optimal care of this vulnerable population. PMID- 25137110 TI - A public health initiative for reducing access to pesticides as a means to committing suicide: findings from a qualitative study. AB - Widespread use of pesticides among farmers in rural India, provides an easy means for suicide. A public health initiative involving storage of pesticides in a central storage facility could be a possible strategy for reducing mortality and morbidity related to pesticide poisoning. This qualitative study explored community perceptions towards a central pesticide storage facility in villages in rural South India. Sixteen focus group discussions held with consenting adults from intervention and control villages were followed by eight more a year after initiation of the storage facility. Analysis revealed four themes, namely, reasons for committing suicide and methods used, exposure to pesticides and first aid practices, storage and disposal of pesticides, and perceptions towards the storage facility. The facility was appreciated as a means of preventing suicides and for providing a safe haven for pesticide storage. The participatory process that guided its design, construction and location ensured its acceptability. Use of qualitative methods helped provide deep insights into the phenomenon of pesticide suicide and aided the understanding of community perceptions towards the storage facility. The study suggests that communal storage of pesticides could be an important step towards reducing pesticide suicides in rural areas. PMID- 25137111 TI - Building mental health workforce capacity through training and retention of psychiatrists in Zimbabwe. AB - Despite the need to improve the quantity and quality of psychiatry training in sub-Saharan Africa (SSA), very little is known about the experiences of psychiatric trainees in the region. This is the first study examining psychiatric trainees in a low-income country in SSA. It was carried out as part of the needs assessment for a unique Medical Education Partnership Initiative (MEPI) programme to find African solutions for medical shortages in Africa. We approached all doctors who had trained in post-graduate psychiatry in Zimbabwe in 2010 and conducted in-depth qualitative interviews with all except one (n = 6). We analysed the data using constant comparison and thematic analysis. Trainees described the apprenticeship model as the programme's primary strength, through providing clinical exposure and role models. Programme weaknesses included shortages in information sources, trainee salaries, trainers, public health education, and in the mental health service. Most respondents were, however, eager to continue practising psychiatry in Zimbabwe, motivated by family ties, national commitment and helping vulnerable, stigmatized individuals. Respondents called for sub-speciality training and for infrastructure and training to do research. Resources need to be made available for psychiatric trainees in more SSA settings to develop public health competencies. However, investment in psychiatry training programmes must balance service provision with trainees' educational needs. Directing investment towards needs identified by trainees may be a cost-effective, context-sensitive way to increase retention and learning outcomes. PMID- 25137112 TI - Corporate social responsibility and mental health: the Premier League football Imagine Your Goals programme. AB - Football is increasingly used to facilitate recovery in mental health services, often in partnership with football clubs. However, few clubs have made mental health part of their corporate social responsibility programmes until recently. We report the impact on participants of the 'Imagine Your Goals' programme, run by 16 Premier League football clubs in conjunction with England's Time to Change programme to reduce mental health-related stigma and discrimination. Mixed methods evaluation used pre/post measures of well-being, access to social capital, focus groups held early on and towards the end of the two-year programmes, and questionnaires for coaching staff. There were no significant changes to participants' mental well-being scores between baseline and follow-up, nor to the total number of social resources accessible through their networks. However, there was a statistically significant increase at follow-up in the mean score of the personal skills subscale of the Resource Generator-UK. Participants' individual skills were also higher at follow-up. Qualitative data showed programmes had largely met participants' expectations in terms of socializing, providing structure and improving fitness levels, exceeded expectations in relationships with coaching staff and additional activities, but did not always meet them in improving football skills. Participants varied in their knowledge of exit opportunities, depending on which club's programme they attended. A minority of clubs reported difficulties in recruitment and concerns about planning for the future of the projects. Football clubs and the charitable foundations they set up can successfully deliver programmes to people with mental health problems which improve access to personal skills social capital and have other potential benefits. PMID- 25137113 TI - Mental Health First Aid is an effective public health intervention for improving knowledge, attitudes, and behaviour: a meta-analysis. AB - Mental Health First Aid (MHFA) is a standardized, psychoeducational programme developed to empower the public to approach, support and refer individuals in distress by improving course participants' knowledge, attitudes and behaviours related to mental ill-health. The present paper aims to synthesize published evaluations of the MHFA programme in a meta-analysis to estimate its effects and potential as a public mental health awareness-increasing strategy. Fifteen relevant papers were identified through a systematic literature search. Standardized effect sizes were calculated for three different outcome measures: change in knowledge, attitudes, and helping behaviours. The results of the meta analysis for these outcomes yielded a mean effect size of Glass's Delta = 0.56 (95% CI = 0.38 - 0.74; p < 0.001), 0.28 (95% CI = 0.22 - 0.35; p < 0.001) and 0.25 (95% CI = 0.12 - 0.38; p < 0.001), respectively. Results were homogenous, and moderator analyses suggested no systematic bias or differences in results related to study design (with or without control group) or 'publication quality' (journal impact factor). The results demonstrate that MHFA increases participants' knowledge regarding mental health, decreases their negative attitudes, and increases supportive behaviours toward individuals with mental health problems. The MHFA programme appears recommendable for public health action. PMID- 25137114 TI - Social support network typologies and health outcomes of older people in low and middle income countries--a 10/66 Dementia Research Group population-based study. AB - This study aims to assess the construct validity of the Wenger social support network typology in low and middle income countries. We hypothesize that, in comparison with the integrated network type, the non-integrated network type is associated with loneliness, depression, poor quality of life (less happiness), poor self-reported health, increased disability and higher care needs. Cross sectional one-phase surveys were conducted of all residents aged 65 and over in catchment areas in eight low and middle income countries (India, China, Cuba, Dominican Republic, Venezuela, Mexico, Peru and Puerto Rico). Wenger's Practitioner Assessment of Network Type (PANT) was used to measure social network type. Family dependent, local self-contained, wider community-focused and private restricted network types were considered non-integrated, in comparison to the locally integrated network type. Overall, 17,031 participants were interviewed. Family dependent and locally integrated network types were the most prevalent. Adjusted pooled estimates across sites showed that loneliness, depression, less happiness, poor health, disability, and need for care were significantly associated with non-integrated network type. The findings of this study support the construct validity of Wenger's network typology in low and middle income countries. However, further research is required to test the criterion validity of Wenger typology using longitudinal data. Identifying older people who are vulnerable could inform the development of social care interventions to support older people and their families in the context of deteriorating health. PMID- 25137115 TI - Eating disorders as a public health issue: prevalence and attributable impairment of quality of life in an Italian community sample. AB - The prevalence of eating disorders (ED) in the community is still under debate, as well as the measure of their impact on the well-being of individuals. It was decided to evaluate the prevalence of eating disorders in an Italian community sample as well as to measure the burden of the quality of life of people and to compare it to those attributable to other chronic illnesses. A community survey of 4,999 people using a questionnaire on health services utilization, the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), a semi structured clinical interview derived from the non-patient version of the DSM-IV (SCID/NP) and Short Form Health Survey (SF-12) was conducted. A total of 3,398 individuals were interviewed (68% of those recruited). Lifetime prevalence for overall ED was 1.7%; for anorexia 0.7%; for bulimia 0.6% and for binge eating disorder 0.5%. ED was more frequent in women than in men. No cases of anorexia in men were identified. ED showed an attributable burden in impairing quality of life with no statistically significant differences with those due to major depressive disorder, bipolar spectrum disorders and Wilson's disease. Of the pathological conditions considered, only multiple sclerosis showed a worsening attributable burden. ED thus has a non-negligible frequency in Italy, with severe impact on quality of life comparable to that produced by severe chronic psychiatric and general medical conditions. These elements emphasize that ED is a serious public health issue. PMID- 25137116 TI - Preparation for parenthood programme: experiences from southern India. AB - Parenting skills are critically important to ensure that children are brought up in a safe environment. Recent evidence shows that studies of parenting skills are still at a preliminary stage in low- and middle-income countries. These need to involve family practitioners and religious groups who often play a major role in preparing young people in India. There are organized programmes available in the country for Christian adults to prepare themselves for marriage and family life through various church initiatives and activities. In order to develop a programme which can be used to prepare young parents for responsibilities of parenthood, a needs assessment was carried out among 70 young adults who attended a marriage preparation course in Bangalore, India. All the participants belonged to the Christian faith. Participants consisted of 53% men and 47% women whose average age for deciding to get married was 26.8 years. All of them expressed a need for such a preparatory programme for parenthood. They considered they needed to know about normal child development, behavioural management of children, to develop adequate skills in handling children at different ages, and deal with their own past issues with their own parents when they were being parented. The results suggest that the development of a preparatory programme for young adults to support them in the role of parenthood must take their views and needs into account. PMID- 25137117 TI - Psychological well-being of parents and family caregivers of children with hearing impairment in south India: influence of behavioural problems in children and social support. AB - Parents of children with hearing impairment are at increased risk of mental health morbidities. We examined the predictive factors associated with caregiver's strain and psychological morbidities in parents and family caregivers of children with hearing impairment. In total, n = 201 parents and family caregivers of children with and without hearing impairment aged 3 to 16 years were recruited. Caregiver's strain and psychological morbidities were measured using the Zarit Burden scale and the World Health Organization's Self-Reporting Questionnaire (SRQ-20). Presence of behavioural problems in children was measured using the Strengths and Difficulties Questionnaire. After adjustment, low educational attainment and domestic violence were found to be associated with caregiving strain, whereas dissatisfaction with social support from family, behavioural problems in children, and domestic violence strongly predicted psychological morbidities. Addressing the mental healthcare needs of parents may help in downsizing the impact of psychological morbidities on the well-being of children with hearing impairment. PMID- 25137118 TI - ICD-10 mental and behavioural disorders due to use of crack and powder cocaine as treated at a public psychiatric emergency service: an analysis of visit predictors. AB - The present study investigated the predictors of an increased number of visits from individuals with some of the diagnoses noted in chapter F14 of ICD-10, from calls to the emergency psychiatric unit of a general hospital in Sao Paulo state, Brazil, in the period 2011-2012. Poisson regression models were carried out for the outcome variable, accounting for number of subsequent visits to the psychiatric emergency unit. For the analysis of this outcome we took into account the exposure time of each individual in the study. Our findings point to a population at risk for frequent psychiatric emergency service visits: individuals over 25 years. This population should be targeted for interventions on entry into public healthcare due to increased psychiatric morbidity and greater clinical morbidity already confirmed by previous studies. We discussed the need of these individuals for special attention during the clinical or psychiatric emergency consultation which, unfortunately, may be the access point for the public health system. None of the other variables were related to the outcome of interest, such as those related to the level of individual entry into the care network before and after treatment, and other variables related to medical acts during the visit. PMID- 25137119 TI - Retention predictors of a smoking treatment provided by a public psychosocial unit in Brazil. AB - Psychosocial units in Brazil (CAPS) provide access to mental health and addiction patients, who are not routinely treated for nicotine dependence. The present study analysed predictors of retention of a 6-week treatment provided by a CAPS unit to 367 smokers with a high rate of psychiatric disorders and addictions for the period 2007-2010. Several baseline variables were collected. Retention was defined as the presence of the individual in all four medical consultations and six group sessions. Multivariate discrete time Cox survival regression models were used to test for the outcome of interest. Timetables were used to explore in which moment of the treatment each predictor was important. Time to smoking the first cigarette (TTFC) 5 min or later after waking and nicotine patch use (nicotine replacement therapy, NRT) were associated with retention. The present study supports the importance of the variables TTFC and NRT when used in treatment retention for a sample with a high rate of psychiatric and alcohol disorders. NRT seems to be very important in the beginning of the treatment, probably because of withdrawal symptoms. Individuals currently undergoing psychiatric treatment and with alcohol problems had good retention rates comparable to the other individuals. PMID- 25137120 TI - The right to health in Paraguay. AB - Access to facilities, services and opportunities designed to meet the needs of health is a fundamental human right and is the key for people to enjoy other human rights. However, in Paraguay, this right is still far from becoming reality. The status of the country is the most disadvantaged when compared to the average condition of the Mercosur (Argentina, Bolivia, Brazil, Paraguay, Uruguay and Venezuela). Health, as a human right, expands as a social, economic, and political matter. Inequality, poverty, exploitation, violence and injustice are at the root of its poor quality and the consequent shortcomings that emerge from it. Access to health in Paraguay must be further developed using a human rights framework linking it with improving quality of life for all citizens. Such an approach means that potentially powerful barriers and interests must be questioned and contested wherever appropriate and that political and economic priorities must change drastically. PMID- 25137121 TI - The crisis in psychiatry: a public health perspective. AB - The role and responsibilities of psychiatry and psychiatrists have changed significantly in recent decades as a consequence of changes in society. The target of psychiatrists has moved from the treatment of specific mental disorders to the management of a wide range of psychological conditions. Following these changes, a public health approach has been claimed as necessary for psychiatric practice and research, given the current ongoing crisis in mental health. If we want to promote a public health approach, the following actions should be responsibly taken by modern mental health professionals: (1) the identification of causes of mental disorders, (2) the refinement of diagnoses, (3) the social inclusion of patients, (4) the involvement of users and carers in mental health research and practice, and (5) the improvement of psychiatric treatments and services. This crisis should represent a stimulus for all psychiatrists and a reconceptualization of psychiatry as public health is not in question. PMID- 25137125 TI - Effect of hydration on the kinetics of proton-bound dimer formation: experimental and theoretical study. AB - A kinetic study was performed on the proton-bound dimer formation of cyclopentanone, cyclohexanone, and cycloheptanone at atmospheric pressure with ion mobility spectrometry (IMS) at the temperature range of 30 to 70 degrees C. Measured rate constants were in the range of 9.5 * 10(-11) to 4.5 * 10(-10) cm(3) s(-1). Rate constants were also calculated using average dipole orientation (ADO) theory employing density functional theory (DFT). Calculated rate constants were in the range of 1.0-5.5 * 10(-9) cm(3) s(-1). The difference between experimental and calculated rate constants was interpreted based on the hydration of the protonated monomers so that water molecules were replaced with a neutral monomer molecule in the process of dimer formation. This process requires activation energy for the formation of dimer and consequently reduces the rate constants. To verify our hypothesis, an effective rate constant (keff) was introduced, which accounted for the energetically activated water-monomer replacement in the dimer formation reactions. A good agreement was observed between the experimental rate constants and calculated keff, confirming the validity of the proposed model in explaining the kinetics of dimer formation in atmospheric pressure. PMID- 25137126 TI - Interface engineering for CVD graphene: current status and progress. AB - In the past decade, graphene and graphene-like 2D materials have drawn more and more attention in both academia and industry due to their fascinating properties. As an atomically thin 2D layered material, graphene has extremely high environmental susceptibility, that is, its properties are strongly affected by its surroundings. In this review, the current status and progress in graphene interface engineering are systematically discussed, including the interface between graphene (carbon sources) and an underlying growth substrate (catalyst), the interface between graphene and a supporting layer during a transfer process, as well as the interface between graphene and a modified substrate from the viewpoint of device applications. These key techniques involved in graphene synthesis, transfer, and device substrates can be further applied to other related 2D layered materials such as MoS2 . Moreover, by combining 2D crystals in one particular stack, 2D-based heterostructures with desired functionalities can be achieved, which opens up a new avenue for the future applications of 2D layered materials. PMID- 25137123 TI - Spatio-temporal analyses of Symbiodinium physiology of the coral Pocillopora verrucosa along large-scale nutrient and temperature gradients in the Red Sea. AB - Algal symbionts (zooxanthellae, genus Symbiodinium) of scleractinian corals respond strongly to temperature, nutrient and light changes. These factors vary greatly along the north-south gradient in the Red Sea and include conditions, which are outside of those typically considered optimal for coral growth. Nevertheless, coral communities thrive throughout the Red Sea, suggesting that zooxanthellae have successfully acclimatized or adapted to the harsh conditions they experience particularly in the south (high temperatures and high nutrient supply). As such, the Red Sea is a region, which may help to better understand how zooxanthellae and their coral hosts successfully acclimatize or adapt to environmental change (e.g. increased temperatures and localized eutrophication). To gain further insight into the physiology of coral symbionts in the Red Sea, we examined the abundance of dominant Symbiodinium types associated with the coral Pocillopora verrucosa, and measured Symbiodinium physiological characteristics (i.e. photosynthetic processes, cell density, pigmentation, and protein composition) along the latitudinal gradient of the Red Sea in summer and winter. Despite the strong environmental gradients from north to south, our results demonstrate that Symbiodinium microadriaticum (type A1) was the predominant species in P. verrucosa along the latitudinal gradient. Furthermore, measured physiological characteristics were found to vary more with prevailing seasonal environmental conditions than with region-specific differences, although the measured environmental parameters displayed much higher spatial than temporal variability. We conclude that our findings might present the result of long-term acclimatization or adaptation of S. microadriaticum to regionally specific conditions within the Red Sea. Of additional note, high nutrients in the South correlated with high zooxanthellae density indicating a compensation for a temperature-driven loss of photosynthetic performance, which may prove promising for the resilience of these corals under increase of temperature increase and eutrophication. PMID- 25137128 TI - Three-dimensional titanium dioxide nanomaterials. PMID- 25137124 TI - Bioinformatic indications that COPI- and clathrin-based transport systems are not present in chloroplasts: an Arabidopsis model. AB - Coated vesicle transport occurs in the cytosol of yeast, mammals and plants. It consists of three different transport systems, the COPI, COPII and clathrin coated vesicles (CCV), all of which participate in the transfer of proteins and lipids between different cytosolic compartments. There are also indications that chloroplasts have a vesicle transport system. Several putative chloroplast localized proteins, including CPSAR1 and CPRabA5e with similarities to cytosolic COPII transport-related proteins, were detected in previous experimental and bioinformatics studies. These indications raised the hypothesis that a COPI- and/or CCV-related system may be present in chloroplasts, in addition to a COPII related system. To test this hypothesis we bioinformatically searched for chloroplast proteins that may have similar functions to known cytosolic COPI and CCV components in the model plants Arabidopsis thaliana and Oryza sativa (subsp. japonica) (rice). We found 29 such proteins, based on domain similarity, in Arabidopsis, and 14 in rice. However, many components could not be identified and among the identified most have assigned roles that are not related to either COPI or CCV transport. We conclude that COPII is probably the only active vesicle system in chloroplasts, at least in the model plants. The evolutionary implications of the findings are discussed. PMID- 25137129 TI - Molecular dynamics simulations of tri-n-butyl-phosphate/n-dodecane mixture: thermophysical properties and molecular structure. AB - Molecular dynamics simulations of tri-n-butyl-phosphate (TBP)/n-dodecane mixture in the liquid phase have been carried out using two recently developed TBP force field models (J. Phys. Chem. B 2012, 116, 305) in combination with the all-atom optimized potentials for liquid simulations (OPLS-AA) force field model for n dodecane. Specifically, the electric dipole moment of TBP, mass density of the mixture, and the excess volume of mixing were computed with TBP mole fraction ranging from 0 to 1. It is found that the aforementioned force field models accurately predict the mass density of the mixture in the entire mole fraction range. Commensurate with experimental measurements, the electric dipole moment of the TBP was found to slightly increase with the mole fraction of TBP in the mixture. Also, in accord with experimental data, the excess volume of mixing is positive in the entire mole fraction range, peaking at TBP mole fraction range 0.3-0.5. Finally, a close examination of the spatial pair correlation functions between TBP molecules, and between TBP and n-dodecane molecules, revealed formation of TBP dimers through self-association at close distance, a phenomenon with ample experimental evidence. PMID- 25137127 TI - Transcription, reverse transcription, and analysis of RNA containing artificial genetic components. AB - Expanding the synthetic biology of artificially expanded genetic information systems (AEGIS) requires tools to make and analyze RNA molecules having added nucleotide "letters". We report here the development of T7 RNA polymerase and reverse transcriptase to catalyze transcription and reverse transcription of xNA (DNA or RNA) having two complementary AEGIS nucleobases, 6-amino-5-nitropyridin-2 one (trivially, Z) and 2-aminoimidazo[1,2a]-1,3,5-triazin-4(8H)-one (trivially, P). We also report MALDI mass spectrometry and HPLC-based analyses for oligomeric GACUZP six-letter RNA and the use of ribonuclease (RNase) A and T1 RNase as enzymatic tools for the sequence-specific degradation of GACUZP RNA. We then applied these tools to analyze the GACUZP and GACTZP products of polymerases and reverse transcriptases (respectively) made from DNA and RNA templates. In addition to advancing this 6-letter AEGIS toward the biosynthesis of proteins containing additional amino acids, these experiments provided new insights into the biophysics of DNA. PMID- 25137130 TI - Identification of phosphopeptides with unknown cleavage specificity by a de novo sequencing assisted database search strategy. AB - In theory, proteases with broad cleavage specificity could be applied to digest protein samples to improve the phosphoproteomic analysis coverage. However, in practice this approach is seldom employed. This is because the identification of phosphopeptides without enzyme specificity by conventional database search strategy is extremely difficult due to the huge search space. In this study, we investigated the performance of a de novo sequencing assisted database search strategy for the identification of such phosphopeptides. Firstly, we compared the performance of conventional database search strategy and the de novo sequencing assisted database search strategy for the identification of peptides and phosphopeptides without stetting enzyme specificity. It was found that the identification sensitivity dropped significantly for the conventional one while it was only slightly decreased for the new approach. Then, this new search strategy was applied to identify phosphopeptides generated by Proteinase K digestion, which resulted in the identification of 717 phosphopeptides. Finally, this strategy was utilized for the identification of serum endogenous phosphopeptides, which were generated in vivo by different kinds of proteases and kinases, and the identification of 68 unique serum endogenous phosphopepitdes was successfully achieved. PMID- 25137131 TI - Grape seed extract improves epithelial structure and suppresses inflammation in ileum of IL-10-deficient mice. AB - Defect in intestinal epithelial structure is a critical etiological factor of several intestinal diseases such as inflammatory bowel disease. The objective of this study was to evaluate the effect of grape seed extract (GSE), which contains a mixture of polyphenols, on ileal mucosal structure and inflammation in interleukin (IL)-10-deficient mice, a common model for studying inflammatory bowel disease. Wild-type and IL-10-deficient mice were fed GSE at 0 or 1% (based on dry feed weight) for 16 weeks. GSE supplementation decreased crypt depth and increased (P < 0.05) the ratio of villus/crypt length in the terminal ileum. Consistently, the dietary GSE decreased (P < 0.05) proliferation and enhanced (P < 0.05) differentiation of epithelial cells. These changes in gut epithelium were associated with the suppression of nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-kappaB) signaling. Furthermore, compared with WT mice, IL-10 deletion promoted beclin-1 and AMPK expression, both of which were decreased to normal by GSE supplementation. These changes were associated with alterations in epithelial barrier function as indicated by reduced pore forming claudin-2 protein expression and increased barrier forming claudin-1 protein expression in the ileum of GSE supplemented mice. In summary, our data indicates that GSE exerts protective effects to the ileal epithelial structure in IL-10-deficient mice possibly through the suppression of inflammatory response. PMID- 25137135 TI - Local coordination geometry perturbed beta-diketone dysprosium single-ion magnets. AB - A series of three beta-diketone mononuclear dysprosium complexes, namely, Dy(TFI)3(H2O)2 (1), Dy(TFI)3(bpy) (2), and [Dy(TFI)3(Phen)].0.02CHCl3 (3) (TFI = 2-(2,2,2-trifluoroethyl)-1-indone, bpy = 2,2'-bipyridine, phen = 1,10 phenanthroline) have been designed and synthesized. Crystal structure analysis reveals that complexes 1-3 have haveisomorphic structures in which the central Dy(III) ion is eight-coordinated by six oxygen atoms from three TFI ligands and two O/N atoms from auxiliary ligands, forming a distorted bicapped trigonal prismatic geometry for 1, a distorted dodecahedral geometry for 2, and a distorted square antiprismatic geometry for 3, respectively. Magnetic studies indicate that complex 2 with D(2d) symmetry and 3 with D(4d) symmetry exhibit slow magnetic relaxation with barrier heights (U(eff)/k(B)) of 48.8 K for 2 and 57.9 K for 3. Strikingly, the relaxation time (tau) of 0.0258 s for 3 is about 20 times that for 2, which is presumably associated with larger rotation of the SAP surroundings for 3. Further, complexes 2 and 3 exhibit essential magnetic hysteresis loops at 1.8 K. These extend the recent reports of the single-ion magnets (SIMs) of beta-diketone mononuclear dysprosium complexes. PMID- 25137134 TI - A novel reaction of peroxiredoxin 4 towards substrates in oxidative protein folding. AB - Peroxiredoxin 4 (Prx4) is the only endoplasmic reticulum localized peroxiredoxin. It functions not only to eliminate peroxide but also to promote oxidative protein folding via oxidizing protein disulfide isomerase (PDI). In Prx4-mediated oxidative protein folding we discovered a new reaction that the sulfenic acid form of Prx4 can directly react with thiols in folding substrates, resulting in non-native disulfide cross-linking and aggregation. We also found that PDI can inhibit this reaction by exerting its reductase and chaperone activities. This discovery discloses an off-pathway reaction in the Prx4-mediated oxidative protein folding and the quality control role of PDI. PMID- 25137133 TI - Mitochondriome and cholangiocellular carcinoma. AB - Cholangiocellular carcinoma (CCA) of the liver was the target of more interest, recently, due mainly to its increased incidence and possible association to new environmental factors. Somatic mitochondrial DNA (mtDNA) mutations have been found in several cancers. Some of these malignancies contain changes of mtDNA, which are not or, very rarely, found in the mtDNA databases. In terms of evolutionary genetics and oncology, these data are extremely interesting and may be considered a sign of poor fitness, which may conduct in some way to different cellular processes, including carcinogenesis. MitoChip analysis is a strong tool for investigations in experimental oncology and was carried out on three CCA cell lines (HuCCT1, Huh-28 and OZ) with different outcome in human and a Papova immortalized normal hepatocyte cell line (THLE-3). Real time quantitative PCR, western blot analysis, transmission electron microscopy, confocal laser microscopy, and metabolic assays including L-Lactate and NAD+/NADH assays were meticulously used to identify mtDNA copy number, oxidative phosphorylation (OXPHOS) content, ultrastructural morphology, mitochondrial membrane potential (DeltaPsim), and differential composition of metabolites, respectively. Among 102 mtDNA changes observed in the CCA cell lines, 28 were non-synonymous coding region alterations resulting in an amino acid change. Thirty-eight were synonymous and 30 involved ribosomal RNA (rRNA) and transfer RNA (tRNA) regions. We found three new heteroplasmic mutations in two CCA cell lines (HuCCT1 and Huh 28). Interestingly, mtDNA copy number was decreased in all three CCA cell lines, while complexes I and III were decreased with depolarization of mitochondria. L Lactate and NAD+/NADH assays were increased in all three CCA cell lines. MtDNA alterations seem to be a common event in CCA. This is the first study using MitoChip analysis with comprehensive metabolic studies in CCA cell lines potentially creating a platform for future studies on the interactions between normal and neoplastic cells. PMID- 25137136 TI - Integrating multi-omics for uncovering the architecture of cross-talking pathways in breast cancer. AB - Cross-talk among abnormal pathways widely occurs in human cancer and generally leads to insensitivity to cancer treatment. Moreover, alterations in the abnormal pathways are not limited to single molecular level. Therefore, we proposed a strategy that integrates a large number of biological sources at multiple levels for systematic identification of cross-talk among risk pathways in cancer by random walk on protein interaction network. We applied the method to multi-Omics breast cancer data from The Cancer Genome Atlas (TCGA), including somatic mutation, DNA copy number, DNA methylation and gene expression profiles. We identified close cross-talk among many known cancer-related pathways with complex change patterns. Furthermore, we identified key genes (linkers) bridging these cross-talks and showed that these genes carried out consistent biological functions with the linked cross-talking pathways. Through identification of leader genes in each pathway, the architecture of cross-talking pathways was built. Notably, we observed that linkers cooperated with leaders to form the fundamentation of cross-talk of pathways which play core roles in deterioration of breast cancer. As an example, we observed that KRAS showed a direct connection to numerous cancer-related pathways, such as MAPK signaling pathway, suggesting that it may be a central communication hub. In summary, we offer an effective way to characterize complex cross-talk among disease pathways, which can be applied to other diseases and provide useful information for the treatment of cancer. PMID- 25137138 TI - Germination shifts of C3 and C4 species under simulated global warming scenario. AB - Research efforts around the world have been increasingly devoted to investigating changes in C3 and C4 species' abundance or distribution with global warming, as they provide important insight into carbon fluxes and linked biogeochemical cycles. However, changes in the early life stage (e.g. germination) of C3 and C4 species in response to global warming, particularly with respect to asymmetric warming, have received less attention. We investigated germination percentage and rate of C3 and C4 species under asymmetric (+3/+6 degrees C at day/night) and symmetric warming (+5/+5 degrees C at day/night), simulated by alternating temperatures. A thermal time model was used to calculate germination base temperature and thermal time constant. Two additional alternating temperature regimes were used to test temperature metrics effect. The germination percentage and rate increased continuously for C4 species, but increased and then decreased with temperature for C3 species under both symmetric and asymmetric warming. Compared to asymmetric warming, symmetric warming significantly overestimated the speed of germination percentage change with temperature for C4 species. Among the temperature metrics (minimum, maximum, diurnal temperature range and average temperature), maximum temperature was most correlated with germination of C4 species. Our results indicate that global warming may favour germination of C4 species, at least for the C4 species studied in this work. The divergent effects of asymmetric and symmetric warming on plant germination also deserve more attention in future studies. PMID- 25137137 TI - A novel cell line derived from pleomorphic adenoma expresses MMP2, MMP9, TIMP1, TIMP2, and shows numeric chromosomal anomalies. AB - Pleomorphic adenoma is the most common salivary gland neoplasm, and it can be locally invasive, despite its slow growth. This study aimed to establish a novel cell line (AP-1) derived from a human pleomorphic adenoma sample to better understand local invasiveness of this tumor. AP-1 cell line was characterized by cell growth analysis, expression of epithelial and myoepithelial markers by immunofluorescence, electron microscopy, 3D cell culture assays, cytogenetic features and transcriptomic study. Expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) was also analyzed by immunofluorescence and zymography. Furthermore, epithelial and myoepithelial markers, MMPs and TIMPs were studied in the tumor that originated the cell line. AP-1 cells showed neoplastic epithelial and myoepithelial markers, such as cytokeratins, vimentin, S100 protein and smooth-muscle actin. These molecules were also found in vivo, in the tumor that originated the cell line. MMPs and TIMPs were observed in vivo and in AP-1 cells. Growth curve showed that AP-1 exhibited a doubling time of 3.342 days. AP-1 cells grown inside Matrigel recapitulated tumor architecture. Different numerical and structural chromosomal anomalies were visualized in cytogenetic analysis. Transcriptomic analysis addressed expression of 7 target genes (VIM, TIMP2, MMP2, MMP9, TIMP1, ACTA2 e PLAG1). Results were compared to transcriptomic profile of non-neoplastic salivary gland cells (HSG). Only MMP9 was not expressed in both libraries, and VIM was expressed solely in AP-1 library. The major difference regarding gene expression level between AP-1 and HSG samples occurred for MMP2. This gene was 184 times more expressed in AP-1 cells. Our findings suggest that AP-1 cell line could be a useful model for further studies on pleomorphic adenoma biology. PMID- 25137139 TI - The CRISPR/Cas9 System Facilitates Clearance of the Intrahepatic HBV Templates In Vivo. AB - Persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) under current antiviral therapy is a major barrier to eradication of chronic hepatitis B (CHB). Curing CHB will require novel strategies for specific disruption of cccDNA. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is a newly developed tool for site-specific cleavage of DNA targets directed by a synthetic guide RNA (gRNA) base-paired to the target DNA sequence. To examine whether this system can cleave HBV genomes, we designed eight gRNAs against HBV of genotype A. With the HBV-specific gRNAs, the CRISPR/Cas9 system significantly reduced the production of HBV core and surface proteins in Huh-7 cells transfected with an HBV-expression vector. Among eight screened gRNAs, two effective ones were identified. Interestingly, one gRNA targeting the conserved HBV sequence acted against different genotypes. Using a hydrodynamics-HBV persistence mouse model, we further demonstrated that this system could cleave the intrahepatic HBV genome-containing plasmid and facilitate its clearance in vivo, resulting in reduction of serum surface antigen levels. These data suggest that the CRISPR/Cas9 system could disrupt the HBV-expressing templates both in vitro and in vivo, indicating its potential in eradicating persistent HBV infection. PMID- 25137141 TI - Forensic interpretation of molecular variation on networks of disease transmission and genetic inheritance. AB - This paper describes the inference-on-networks (ION) framework for forensic interpretat ION of molecular typing data in cases involving allegations of infectious microbial transmission, association of disease outbreaks with alleged sources, and identifying familial relationships using mitochondrial or Y chromosomal DNA. The framework is applicable to molecular typing data obtained using any technique, including those based on electrophoretic separations. A key insight is that the networks associated with disease transmission or DNA inheritance can be used to define specific testable relationships and avoid the ambiguity and subjectivity associated with the criteria used for inferring genetic relatedness now in use. We discuss specific applications of the framework to the 2003 severe acute respiratory syndrome (SARS) outbreak in Singapore and the 2001 foot-and-mouth disease virus (FMDV) outbreak in Great Britain. PMID- 25137140 TI - The MicroRNA Biology of the Mammalian Nucleus. AB - MicroRNAs (miRNAs) are a class of genome-encoded small RNAs that are primarily considered to be post-transcriptional negative regulators of gene expression acting in the cytoplasm. Over a decade of research has focused on this canonical paradigm of miRNA function, with many success stories. Indeed, miRNAs have been identified that act as master regulators of a myriad of cellular processes, and many miRNAs are promising therapeutic targets or disease biomarkers. However, it is becoming increasingly apparent that the canonical view of miRNA function is incomplete. Several lines of evidence now point to additional functions for miRNAs in the nucleus of the mammalian cell. The majority of cellular miRNAs are present in both the nucleus and the cytoplasm, and certain miRNAs show specific nuclear enrichment. Additionally, some miRNAs colocalize with sub-nuclear structures such as the nucleolus and chromatin. Multiple components of the miRNA processing machinery are present in the nuclear compartment and are shuttled back and forth across the nuclear envelope. In the nucleus, miRNAs act to regulate the stability of nuclear transcripts, induce epigenetic alterations that either silence or activate transcription at specific gene promoters, and modulate cotranscriptional alternative splicing events. Nuclear miRNA-directed gene regulation constitutes a departure from the prevailing view of miRNA function and as such, warrants detailed further investigation. PMID- 25137143 TI - Lactase persistence and dairy intake in Mapuche and Mestizo populations from southern Chile. AB - Lactase persistence (LP) occurs at a very low frequency in indigenous populations from Latin America, offering an opportunity to understand the relationship between this genetic trait and patterns of dairy consumption. Here, the frequency of LP is analyzed from Mapuche and -an adjacent- mestizo population inhabiting the Araucania region. In addition to genotyping for LP, participants were surveyed in relation to general perception and consumption habits of dairy products. Low LP frequency (10%) and very low dairy intake was found among the Mapuche population as compared with Mestizo populations inhabiting Chile. The survey reported that the main reasons for avoidance of dairy were the gastrointestinal symptoms after dairy intake and cultural dietary habits. The interaction between low LP genotype frequency, low dairy intake, and sociocultural determinants is here discussed in the light of their potential health outcomes. PMID- 25137142 TI - The cytoplasmic capping complex assembles on adapter protein nck1 bound to the proline-rich C-terminus of Mammalian capping enzyme. AB - Cytoplasmic capping is catalyzed by a complex that contains capping enzyme (CE) and a kinase that converts RNA with a 5'-monophosphate end to a 5' diphosphate for subsequent addition of guanylic acid (GMP). We identify the proline-rich C terminus as a new domain of CE that is required for its participation in cytoplasmic capping, and show the cytoplasmic capping complex assembles on Nck1, an adapter protein with functions in translation and tyrosine kinase signaling. Binding is specific to Nck1 and is independent of RNA. We show by sedimentation and gel filtration that Nck1 and CE are together in a larger complex, that the complex can assemble in vitro on recombinant Nck1, and Nck1 knockdown disrupts the integrity of the complex. CE and the 5' kinase are juxtaposed by binding to the adjacent domains of Nck1, and cap homeostasis is inhibited by Nck1 with inactivating mutations in each of these domains. These results identify a new domain of CE that is specific to its function in cytoplasmic capping, and a new role for Nck1 in regulating gene expression through its role as the scaffold for assembly of the cytoplasmic capping complex. PMID- 25137144 TI - Percutaneous radiofrequency facet joint denervation with monitoring of compound muscle action potential of the multifidus muscle group for treating chronic low back pain: a preliminary report. AB - STUDY DESIGN: A retrospective review. OBJECTIVE: The aim of this study was to study the effectiveness of percutaneous radiofrequency neurotomy of facet joints by monitoring compound muscle action potentials (CMAPs) of the multifidus muscle group as an objective index of treatment efficacy. SUMMARY OF BACKGROUND: Percutaneous radiofrequency neurotomy of the medial branches of the dorsal rami of the lumbar nerves is a widely accepted treatment for chronic lumbar intervertebral joint pain. However, its success rate has varied in different studies because an objective method for evaluating the facet joint denervation is lacking. METHODS: Fifty-five patients (age range, 19-76 y; mean age, 55 y) with low back pain persisting for >=3 months, in whom facet block and/or block of the medial branch of the dorsal ramus were only temporarily effective, were included. The Japanese Orthopaedic Association (JOA) scoring system for back pain was used for clinical assessment. JOA scores were measured before treatment and 1 week, 3 months, 6 months, and 12 months afterward. The improvement rate was calculated with >=40% improvement rate defined as successful, and the success rate was subsequently evaluated. RESULTS: The patient success rate was 75% (41/55) at 1 week, 71% (39/55) at 3 months, 60% (33/55) at 6 months, and 51% (28/55) at 12 months after treatment. Two cases had minor postoperative complications, which were localized burning pain lasting <1 week at the site of electrode insertion. CONCLUSIONS: Our results suggest that percutaneous radiofrequency facet joint denervation with CMAPs monitoring is a safe, long-lasting, and effective treatment for chronic facet joint pain. CMAP monitoring may be useful as an objective index for facet denervation. PMID- 25137146 TI - Reduced Endotracheal Tube Cuff Pressure to Assess Dysphagia After Anterior Cervical Spine Surgery. AB - STUDY DESIGN: This was a prospective, randomized control pilot study. OBJECTIVE: The aim of this study was to determine whether continuous monitoring and adjustment of the endotracheal tube cuff pressure (ETTCP) to 15 mm Hg during ACSS would alter the incidence of postoperative dysphagia. SUMMARY OF BACKGROUND DATA: Postoperative dysphagia is a recognized potential complication of anterior cervical spine surgery (ACSS). Recent findings on preventive measures suggest that certain intraoperative practices may minimize this complication. METHODS: Fifty patients undergoing ACSS, arthroplasty, or fusion, completed routine lateral cervical preoperative plain films and questionnaires [Dysphagia Disability Index (DDI), Bazaz-Yoo Dysphagia Score (BYDS), and Short Form (36) Health Survey]. Patients were randomized into 2 groups: treatment group with ETTCP maintained at 15 mm Hg and control group with cuff pressure monitored without manipulation. Radiographs and questionnaires were obtained at 24 hours, 6 weeks, and 3 and 6 months postsurgery to assess soft tissue thickness and rates of dysphagia. RESULTS: There were no significant differences between the groups in the soft tissue thickness or questionnaire scores at any timepoint (P>0.05). Within-group analysis revealed treatment and control groups had a significantly higher 24-hour postoperative soft tissue thickness and questionnaire scores compared with follow-up measurements (P<0.05). In the pooled group (n=50), the 24 hour postoperative DDI, BYDS, and soft tissue thickness were significantly higher compared with all other timepoints (P<0.01). DDI scores >=10 related to dysphagia were in 59% of patients at 24 hours, 35% at 6 weeks, 24% at 3 months, and 18% at 6 months. CONCLUSIONS: This study suggests decreased ETTCP has no effect on the prevalence of dysphagia. The incidence of dysphagia decreases over time and normalizes by 6 months postsurgery. PMID- 25137145 TI - Surgical treatment of large abdominally involved primary dumbbell tumor in the lumbar region. AB - STUDY DESIGN: This was a retrospective clinical study. OBJECTIVE: The aim of this study was to assess the efficacy of a combined anterior and posterior approach, or single-stage posterior extensive approach for resection of large abdominally involved dumbbell tumor in the lumbar region. BACKGROUND: Resection of the large spinal-retroperitoneal involved dumbbell tumor is particularly controversial and challenging because of unique exposure requirements. METHODS: From June 2006 to October 2011, 18 consecutive patients suffering from large dumbbell tumors in the lumbar region were involved. In the initial 8 patients, a combined posterior and anterior surgical approach was applied. The remaining 10 patients were surgically treated with a single posterior extensive approach to excise both the intraspinal and intra-abdominal tumors. Reconstruction with bone or mesh grafts was also performed simultaneously in 3 of the 10 patients in this group. RESULTS: The perioperative period was uneventful for 7 of 8 patients who underwent combined surgery. However, 1 patient encountered right nephrectomy because of a ruptured renal vein and refractory bleeding during anterior tumor exposure. Histopathology revealed the presence of schwannoma (n=4), neurofibroma (n=3), and neuroblastoma (n=1). With the mean of 52 months of follow-up, metastasis occurred in 1 patient with neuroblastoma. In the 10 patients with only the posterior approach, histopathology demonstrated schwannoma (n=5), neurofibroma (n=3), small round cell mesenchymal tumor (n=1), and benign fibrous histiocytoma (n=1). No recurrence was detected at the mean follow-up of 24 months. CONCLUSIONS: The posterior extensive approach is safe and effective to remove the large abdominally involved dumbbell tumors, and also facilitates simultaneously reconstruction of the vertebral body, as compared with the combined posterior and anterior approach. PMID- 25137147 TI - The Reliabilities of Radiographic Measurements of Cervical Sagittal Alignment in Ankylosing Spondylitis. AB - STUDY DESIGN: This is a prospective study design. OBJECTIVE: To test the interobserver and intraobserver reliabilities of 5 specific measures of global cervical sagittal alignment in patients with ankylosing spondylitis (AS), and to suggest a better means of measuring cervical sagittal alignment. SUMMARY OF BACKGROUND DATA: The intraobserver and interobserver reliabilities of several different methods of measuring cervical lordosis have been reported. However, they have not been studied till yet in patients with AS. METHODS: Interobserver and intraobserver reliabilities of 5 specific measures of cervical lordosis were evaluated in patients with AS. Eighty patients with AS were allocated to a nonankylosis or an ankylosis group, and the reliabilities of the Cobb C1-C7, Cobb C2-C7, centroid, posterior tangent, and Ishihara index methods were evaluated. RESULTS: The intraclass and interclass correlation coefficients (ICCs) of all 5 methods were generally high. For the 80 study subjects, ICCs were >=0.84 (excellent) for all 5 radiographic methods. However, comparison of the ICCs, 95% confidence intervals, and mean absolute differences (MAD) between groups with varying degrees of ankylosis showed that the reliability of lordosis measurements decreased as the severity of ankylosis increased. The 5 methods consistently demonstrated higher ICCs for both interobserver and intraobserver comparisons in the nonankylosis group. However, in the ankylosis group, the Cobb C1-C7 method demonstrated high ICCs for both interobserver and intraobserver comparisons, whereas the other 4 methods had high ICCs only for intraobserver comparisons. The intraobserver MADs were similar for the 5 methods (2.4-3.9), but the interobserver MADs of measurement methods in both groups showed low measurement reliability except for the Cobb C1-C7 methods. CONCLUSIONS: This study provides a reliability analysis of different cervical lordosis measurement methods in AS, and shows that the Cobb C1-C7 method provides a reliable means for measuring cervical lordosis in AS. PMID- 25137149 TI - Synthesis of a poly-hydroxypyrolidine-based inhibitor of Mycobacterium tuberculosis GlgE. AB - Long treatment times, poor drug compliance, and natural selection during treatment of Mycobacterium tuberculosis (Mtb) have given rise to extensively drug resistant tuberculosis (XDR-TB). As a result, there is a need to identify new antituberculosis drug targets. Mtb GlgE is a maltosyl transferase involved in alpha-glucan biosynthesis. Mutation of GlgE in Mtb increases the concentration of maltose-1-phosphate (M1P), one substrate for GlgE, causing rapid cell death. We have designed 2,5-dideoxy-3-O-alpha-d-glucopyranosyl-2,5-imino-d-mannitol (9) to act as an inhibitor of GlgE. Compound 9 was synthesized using a convergent synthesis by coupling thioglycosyl donor 14 and 5-azido-3-O-benzyl-5-deoxy-1,2-O isopropylidene-beta-d-fructopyranose (23) to form disaccharide 24. A reduction and intramolecular reductive amination transformed the intermediate disaccharide 24 to the desired pyrolidine 9. Compound 9 inhibited both Mtb GlgE and a variant of Streptomyces coelicolor (Sco) GlgEI with Ki = 237 +/- 27 MUM and Ki = 102 +/- 7.52 MUM, respectively. The results confirm that a Sco GlgE-V279S variant can be used as a model for Mtb GlgE. In conclusion, we designed a lead transition state inhibitor of GlgE, which will be instrumental in further elucidation of the enzymatic mechanism of Mtb GlgE. PMID- 25137150 TI - SDF-1alpha stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II. AB - Multiple myeloma (MM) is a B lymphocyte malignancy that remains incurable despite extensive research efforts. This is due, in part, to frequent disease recurrences associated with the persistence of myeloma cancer stem cells (mCSCs). Bone marrow mesenchymal stromal cells (BMSCs) play critical roles in supporting mCSCs through genetic or biochemical alterations. Previously, we identified mechanical distinctions between BMSCs isolated from MM patients (mBMSCs) and those present in the BM of healthy individuals (nBMSCs). These properties of mBMSC contributed to their ability to preferentially support mCSCs. To further illustrate mechanisms underlying the differences between mBMSCs and nBMSCs, here we report that (i) mBMSCs express an abnormal, constitutively high level of phosphorylated Myosin II, which leads to stiffer membrane mechanics, (ii) mBMSCs are more sensitive to SDF-1alpha-induced activation of MYL2 through the G(i./o)-PI3K-RhoA ROCK-Myosin II signaling pathway, affecting Young's modulus in BMSCs and (iii) activated Myosin II confers increased cell contractile potential, leading to enhanced collagen matrix remodeling and promoting the cell-cell interaction between mCSCs and mBMSCs. Together, our findings suggest that interfering with SDF-1alpha signaling may serve as a new therapeutic approach for eliminating mCSCs by disrupting their interaction with mBMSCs. PMID- 25137152 TI - A longer diagnostic interval is a risk for depression in amyotrophic lateral sclerosis. AB - OBJECTIVE: Recognizing depressive symptoms in patients with amyotrophic lateral sclerosis (ALS) remains problematic given the potential overlap with the normal psychological responses to a terminal illness. Understanding mental health and disease-related risk factors for depression is key to identifying psychological morbidity. The present study aimed to determine the prevalence of depressive symptoms in ALS and to explore mental health and disease-related risk factors for depression. METHOD: Structured medical and psychiatric history questionnaires and a validated depression scale (Depression, Anxiety, Stress Scale-21) were completed by 27 ALS patients (60% female; 59% limb onset; age 65.11 +/- SE 2.21) prior to their initial review at a multidisciplinary clinic. Physical function was assessed with the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). RESULTS: At the time of initial assessment, 44% of patients had a previous psychiatric history, although the majority (62%) reported no symptoms of depression. The mean ALSFRS-R score was 37.78 +/- SE 1.22, with an average diagnostic interval of 16.04 +/- SE 2.39 months. Logistic regression analysis revealed that the length of the diagnostic interval alone predicted depressive symptoms (chi2(3, n = 26) = 9.21, Odds Ratio (OR) = 1.12, p < 0.05. SIGNIFICANCE OF RESULTS: The illness experiences of ALS patients rather than established mental health risk factors influence the manifestation of depressive symptoms in the early stages of the disease, with clinical implications for the assessment and treatment of psychological morbidity. Patients with lengthy diagnostic intervals may be prime targets for psychological assessment and intervention, especially in the absence of ALS-specific tests and biomarkers. PMID- 25137151 TI - Osteogenic gene transcription is regulated via gap junction-mediated cell-cell communication. AB - An analytical study of cell-cell communications between murine osteoblast-like MLO-A5 cells and bone marrow mesenchymal stem cell (BMSC)-like C3H10T1/2 cells was performed. C3H10T1/2 cells expressing green fluorescent protein (10T-GFP cells) were generated to enable the isolation of the BMSC-like cells from co cultures with MLO-A5 cells. The mRNA expression levels of several osteogenic transcription factors (Runx2, Osterix, Dlx5, and Msx2) did not differ between the co-cultured and mono-cultured 10T-GFP cells, but those of alkaline phosphatase (ALP) and bone sialoprotein (BSP) were 300- to 400-fold higher in the co-cultured cells. Patch clamp and biocytin transfer assays revealed gap junction-mediated communication between co-cultured 10T-GFP and MLO-A5 cells. The addition of a gap junction inhibitor suppressed the increases in the expression levels of the ALP and BSP mRNAs in co-cultured 10T-GFP cells. Furthermore, the histone acetylation levels were higher in co-cultured 10T-GFP cells than in mono-cultured 10T-GFP cells. These results suggest that osteoblasts and BMSCs associate via gap junctions, and that gap junction-mediated signaling induces histone acetylation that leads to elevated transcription of the genes encoding ALP and BSP in BMSCs. PMID- 25137155 TI - Application of empirical wave run-up formulas to the Polish Baltic Sea coast. AB - Advanced, multidimensional models are typically applied when researching processes occurring in the nearshore. Relatively simple, empirical equations are commonly used in coastal engineering practice in order to estimate extreme wave run-up on beaches and coastal structures. However, they were mostly calibrated to the characteristics of oceanic coasts, which have different wave regime than a semi-enclosed basin like the Baltic Sea. In this paper we apply the formulas to the Polish Baltic Sea coast. The equations were adjusted to match local conditions in two test sites in Miedzyzdroje and Dziwnowek, where beaches are under continuous video surveillance. Data from WAM wave model and coastal gauge stations were used, as well as precise measurements of the beaches' cross sections. More than 600 run-up events spanning from June to December 2013 were analysed, including surges causing dune erosion. Extreme wave run-up R2% was calculated and presented as a percentage value indicating what part of the beach was inundated. The method had a root-mean-square error of 6.1 and 6.5 percentage points depending on the test site. We consider it is a fast and computationally undemanding alternative to morphodynamic models. It will constitute a part of the SatBaltyk Operating System-Shores, delivering forecasts of wave run-up on the beaches for the entire Polish coastline. PMID- 25137153 TI - Molecular analysis of Aedes aegypti classical protein tyrosine phosphatases uncovers an ortholog of mammalian PTP-1B implicated in the control of egg production in mosquitoes. AB - BACKGROUND: Protein Tyrosine Phosphatases (PTPs) are enzymes that catalyze phosphotyrosine dephosphorylation and modulate cell differentiation, growth and metabolism. In mammals, PTPs play a key role in the modulation of canonical pathways involved in metabolism and immunity. PTP1B is the prototype member of classical PTPs and a major target for treating human diseases, such as cancer, obesity and diabetes. These signaling enzymes are, hence, targets of a wide array of inhibitors. Anautogenous mosquitoes rely on blood meals to lay eggs and are vectors of the most prevalent human diseases. Identifying the mosquito ortholog of PTP1B and determining its involvement in egg production is, therefore, important in the search for a novel and crucial target for vector control. METHODOLOGY/PRINCIPAL FINDINGS: We conducted an analysis to identify the ortholog of mammalian PTP1B in the Aedes aegypti genome. We identified eight genes coding for classical PTPs. In silico structural and functional analyses of proteins coded by such genes revealed that four of these code for catalytically active enzymes. Among the four genes coding for active PTPs, AAEL001919 exhibits the greatest degree of homology with the mammalian PTP1B. Next, we evaluated the role of this enzyme in egg formation. Blood feeding largely affects AAEL001919 expression, especially in the fat body and ovaries. These tissues are critically involved in the synthesis and storage of vitellogenin, the major yolk protein. Including the classical PTP inhibitor sodium orthovanadate or the PTP substrate DiFMUP in the blood meal decreased vitellogenin synthesis and egg production. Similarly, silencing AAEL001919 using RNA interference (RNAi) assays resulted in 30% suppression of egg production. CONCLUSIONS/SIGNIFICANCE: The data reported herein implicate, for the first time, a gene that codes for a classical PTP in mosquito egg formation. These findings raise the possibility that this class of enzymes may be used as novel targets to block egg formation in mosquitoes. PMID- 25137154 TI - Transmission of epi-alleles with MET1-dependent dense methylation in Arabidopsis thaliana. AB - DNA methylation in plants targets cytosines in three sequence contexts, CG, CHG and CHH (H representing A, C or T). Each of these patterns has traditionally been associated with distinct DNA methylation pathways with CHH methylation being controlled by the RNA dependent DNA methylation (RdDM) pathway employing small RNAs as a guide for the de novo DOMAINS REARRANGED METHYLTRANSFERASE (DRM2), and maintenance DNA METHYLTRANSFERASE1 (MET1) being responsible for faithful propagation of CG methylation. Here we report an unusual 'dense methylation' pattern under the control of MET1, with methylation in all three sequence contexts. We identified epi-alleles of dense methylation at a non coding RNA locus (At4g15242) in Arabidopsis ecotypes, with distinct dense methylation and expression characteristics, which are stably maintained and transmitted in genetic crosses and which can be heritably altered by depletion of MET1. This suggests that, in addition to its classical CG maintenance function, at certain loci MET1 plays a role in creating transcriptional diversity based on the generation of independent epi-alleles. Database inspection identified several other loci with MET1-dependent dense methylation patterns. Arabidopsis ecotypes contain distinct epi-alleles of these loci with expression patterns that inversely correlate with methylation density, predominantly within the transcribed region. In Arabidopsis, dense methylation appears to be an exception as it is only found at a small number of loci. Its presence does, however, highlight the potential for MET1 as a contributor to epigenetic diversity, and it will be interesting to investigate the representation of dense methylation in other plant species. PMID- 25137156 TI - Stereoselective synthesis of C-fused pyranoindoles, pyranobenzofurans and pyranobenzothiophene scaffolds using oxa-Pictet-Spengler type reaction of vinylogous carbonates. AB - C-fused pyranoheterocycles can be readily assembled using an intramolecular oxa Pictet-Spengler type reaction of vinylogous carbonates in a highly stereoselective manner. Required indole and benzofuran rings tethered to vinylogous carbonates are prepared by a tandem Sonogashira coupling nucleopalladation reaction. The entire process can also be carried out in a 'one pot' manner starting from homopropargyl alcohol. The C-fused pyranoindoles could be converted to spirooxindoles as well as to ring expanded products under oxidative conditions. PMID- 25137157 TI - Underestimated potential of organometallic rhenium complexes as anticancer agents. AB - In the recent years, organometallic compounds have become recognized as promising anti-cancer drug candidates. While radioactive (186/188)Re compounds are already used in clinics for cancer treatment, cold Re organometallic compounds have mostly been explored as luminescent probes for cell imaging and photosensitizers in photocatalysis. However, a growing number of studies have recently revealed the potential of Re organometallic complexes as anti-cancer agents. Several compounds have displayed cytotoxicity equaling or exceeding that of the well established anti-cancer drug cisplatin. In this review, we present the currently known Re organometallic complexes that have shown anti-proliferative activity on cancer cell lines. A particular emphasis is placed on their cellular uptake and localization as well as their potential mechanism of action. PMID- 25137158 TI - [Cost-minimization analysis of subcutaneous abatacept in the treatment of rheumatoid arthritis in Spain]. AB - OBJECTIVE: To compare the cost of treating rheumatoid arthritis patients that have failed an initial treatment with methotrexate, with subcutaneous abatacept versus other first-line biologic disease-modifying antirheumatic drugs. METHOD: Subcutaneous abatacept was considered comparable to intravenous abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab and tocilizumab, based on indirect comparison using mixed treatment analysis. A cost minimization analysis was therefore considered appropriate. The Spanish Health System perspective and a 3 year time horizon were selected. Pharmaceutical and administration costs (Euros 2013) of all available first-line biological disease modifying antirheumatic drugs were considered. Administration costs were obtained from a local costs database. Patients were considered to have a weight of 70 kg. A 3% annual discount rate was applied. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Subcutaneous abatacept proved in the base case to be less costly than all other biologic antirrheumatic drugs (ranging from Euros -831.42 to Euros -9,741.69 versus infliximab and tocilizumab, respectively). Subcutaneous abatacept was associated with a cost of Euros 10,760.41 per patient during the first year of treatment and Euros 10,261.29 in subsequent years. The total 3-year cost of subcutaneous abatacept was Euros 29,953.89 per patient. Sensitivity analyses proved the model to be robust. Subcutaneous abatacept remained cost-saving in 100% of probabilistic sensitivity analysis simulations versus adalimumab, certolizumab, etanercept and golimumab, in more than 99.6% versus intravenous abatacept and tocilizumab and in 62.3% versus infliximab. CONCLUSIONS: Treatment with subcutaneous abatacept is cost saving versus intravenous abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab and tocilizumab in the management of rheumatoid arthritis patients initiating treatment with biological antirheumatic drugs. PMID- 25137159 TI - [Long-term cost-effectiveness of ticagrelor versus clopidogrel in acute coronary syndrome in Spain]. AB - OBJECTIVE: To assess the cost-effectiveness relationship of Ticagrelor versus Clopidogrel for the management of acute coronary syndrome in Spain. METHODS: The data from the PLATO study were used for the calculation of the events rate and health-related quality of life for Ticagrelor and Clopidogrel for the first 12 months, whereas the costs were obtained from Spanish sources. Quality of life adjusted survival and costs were estimated according to the fact that the patients did not suffer any thrombotic event (myocardial infarction or ictus) or this one was not fatal. The lifetime cots, life years gained, and the quality of life-adjusted survival were estimated for both treatment arms. Incremental cost effectiveness ratios were assessed through the perspective of the Spanish healthcare system for 2013, by using a macro-costs strategy based on published literature and the survival tables for the Spanish population. RESULTS: Treatment with Ticagrelor was associated to an incremental cost of 1,228 Euros per year, an increase in 0.1652 life years gained, and 0.1365 years adjusted by quality of life, as compared to Clopidogrel. The cost for one quality of life-adjusted life year was 8,997 Euros and the cost per one gained life year of 7,435 ?. The sensitivity analysis showed consistent results. CONCLUSIONS: Treatment of acute coronary syndrome for 12 months with Ticagrelor was associated with a cost per 1 life year of quality of life-adjusted cost below the cost-effectiveness limits generally accepted in Spain. PMID- 25137160 TI - [Intravenous drugs infusion safety through smart pumps]. AB - OBJECTIVE: To analyze the role of smart infusion pumps in reducing errors related with the administration of intravenous medications. METHOD: Retrospective, observational study analyzing the implementation of a system with smart intravenous infusion pumps (Hospira MedNetTM) and the role of the safety system for the detection of errors during the administration of drugs, sera, and blood. We included infusions administered at the day-care hospitals of hematology, oncology, rheumatology, and oncopediatrics. We analyzed adherence to the safety system, the number of programming errors detected, the commonly implicated drugs in these errors, and improvement actions. RESULTS: During the study period, 120 smart pumps were implemented and data on 70,028 infusions were gathered. The rate of adherence to the safety program was 62.30% in hematology (6,887 infusions), 60,30% in oncology (28,127 infusions), 46,50% in rheumatology (1,950 infusions) and 1.8% in oncopediatrics (139 infusions). 3,481 out of the established limits programming alerts were generated by the pumps: 2,716 of relative limit and 765 of absolute limit. En 807 infusions (2.17%), errors that could have had consequences for the patients could be prevented. These findings allowed implementing a series of strategies aimed at minimizing these errors in the future. CONCLUSIONS: The Hospira MedNetTM system detects deviations from the established protocols of intravenous infusion, preventing in this way potential adverse events for the patients. It also allows establishing correction measures and implementing the improvement strategies. PMID- 25137161 TI - [Validation of genetic polymorphisms associated to the toxicity of chemotherapy in colorectal cancer patients]. AB - OBJECTIVE: To validate the associations previously found in three cohorts of patients from the General University Hospital Gregorio Maranon, between the polymorphisms rs1128503, rs2032582 and rs1045642 of the ABCB1 gene and the hand foot syndrome and diarrhea in colorectal cancer patients treated with chemotherapy regimes containing Capecitabine and 5-Fluorouracil, respectively, and between the polymorphisms rs2297595 of the DPYD gene and nausea/vomiting, rs11615 of ERCC1 and neutropenia, and rs28399433 CYP2A6 and neutropenia, in colorectal cancer patients treated with FOLFOX or XELOX as adjuvant therapy. METHOD: Colorectal cancer patients treated with chemotherapy regimes, containing Capecitabine (n = 157), 5-Fluorouracil (n = 99) were included in the study, as well as patients treated with XELOX or FOLFOX (n = 83) as adjuvant therapy. The patients included were recruited from the Doce de Octubre University Hospital and from the Gregorio Maranon General University Hospital, and signed the informed consent form. DNA was obtained from blood samples. Genotyping was carried out with SNaPshot. Contingency tables were created for analyzing the associations between the genotypes and the adverse reactions. RESULTS: None of the associations previously identified was replicated in the validation cohort. CONCLUSIONS: Pharmacogenetic studies with a limited sample size must be validated with bigger cohorts, if possible by means of multicentre studies, reducing the variables to the maximum and should never be used in clinical practice without validation. PMID- 25137162 TI - [Adherence, satisfaction and health-related quality of life in HIV-infected patients with antiretroviral therapy in Spain. The ARPAS study]. AB - OBJECTIVE: To determine the relationship between satisfaction with antiretroviral therapy (ART), adherence and quality of life (QoL) in adult patients diagnosed with HIV infection and ART according to the posologic load. METHOD: Multicenter, observational and cross-sectional study. Socio-demographic, clinical and of posologic load (1, 2-4 or > 4 tablets/day), adherence (SMAQ, dispensation recordings (DR) and visual analogical scale), satisfaction (ESART questionnaire) and QoL (MOS-HIV) variables were gathered. An adherent patient was defined as the one presenting simultaneously adherence according to SMAQ and DR > 95%. RESULTS: 328 patients (76% men; 46.0 +/- 9.2 years) were evaluated. The posology of 1 tablet/day, 2-4 tablets/day and > 4 tablets/day occurred in 29%, 37% and 34% of the patients, respectively. Although the evaluation performed through the SMAQ questionnaire and the VAS scale independently showed statistically significant differences in favor of the 1 tablet/day scheme, the percentage (49%) of adherent patients according to the combined variable did not differ between the groups based on the posologic load. The satisfaction with ART and QoL were high in the three groups, being the 1 tablet/day scheme the one related with higher satisfaction and lower rate of adverse effects on fat metabolism. There were no differences in patients' satisfaction by the adherence level. CONCLUSIONS: Adherence, satisfaction with ART and QoL of the patients with ART are high. Although higher in patients taking 1 tablet/day, the satisfaction did not differ according to the level of adherence and no correlation was observed between satisfaction with ART and quality of life. PMID- 25137163 TI - [Analysis of ocular toxicity of fluconazole and voriconazole eyedrops using HET CAM]. AB - PURPOSE: The objective of the study is to provide toxicological information through the HET-CAM test of Fluconazole and Voriconazole eye drops prepared commonly in Pharmacy Services for the treatment of fungal keratitis. METHOD: Experimental Study. The ocular toxicity of topical voriconazole 10 mg/ml and fluconazole 2 mg/ml were evaluated by the hen's egg test (HET) on the chorioallantoic membrane (CAM). The effects on blood vessels were based on its behavior during 300 seconds and processes that may occur at each time, then we calculated the irritation index (is, irritation score). RESULTS AND CONCLUSIONS: Both eye drops, voriconazol and fluconazole have been proven to be safe, since the IS that we obtained was zero for both samples and did not present significant signs of irritation. Therefore, these eyedrops are considered suitable for ocular use from a toxicological point of view. PMID- 25137164 TI - [Prevalence of potentially inappropriate medication in hospitalized elderly patients by using explicit criteria]. AB - INTRODUCTION: Potentially inappropriate medication (PIM) prescribing in older adults is quite prevalent and is associated with an increased risk for adverse drug events, morbidity, and utilization of health care resources. The aim of this study was to determine the prevalence and type of PIM in polypharmacy elderly patients on admission and discharge and the factors associated with their prescription. Just as the applicability of various explicit criteria selected from the literature and adapted to our area. METHODS: We performed a cross sectional study for 12 months (March 2010-February 2011) on 179 polypharmacy elderly patients admitted to an Internal Medicine Department. We created a list of 50 PIM using a Delphi approach based on previous published criteria (Beers, Stopp, BMC and Priscus). Through patient interviews, review of medical records and discharge reconciliation report, we identified the prevalence of PIM in the patients. We also analyzed the relationship between different factors and the prescription of PIM. RESULTS: The prevalence of patients with PIM on admission and discharge were 71% and 48%, respectively. Out of the 50 selected PIM, 27 and 26 were detected on admission and discharge, respectively (55.5% and 57.69% included on STOPP criteria). We detected two factors associated with PIM prescription at discharge: severe-total dependence (OR = 1.8) and prescription of more than 11 drugs (OR = 2). CONCLUSIONS: PIM prevalence in our population is very high (70%), especially at hospital admission. These findings support the need for measures aimed at improving the quality of prescriptions, especially on dependent patients with polypharmacy. PMID- 25137166 TI - Medication non-adherence as a cause of hospital admissions. AB - OBJECTIVES: 1. To determine the profile of patients who are admitted to hospital as a result of non-adherence. 2. To obtain an estimate of the economic impact for the hospital. METHODS: Observational and retrospective study that included patients who were admitted to hospital with a secondary diagnosis of "Personal history of non-compliance with chronic medication" according to International Classification of Diseases, during 2012. DATA COLLECTED: demographics; socioeconomic and clinical data; data related to the treatment; readmissions; hospital days; degree of adherence: <= 75% or severe non-adherence and > 75% or moderate non-adherence; type of non-adherence: non-persistence and noncompliance; hospitalization costs. Statistical analysis was performed. RESULTS: Eighty-seven patients were admitted. These patients caused 104 episodes (16.3% were readmissions). 71.2% were men, and 51.5 (SD 17.8) years old. All patients had a chronic disease, adherence <= 75% (76%) and non-persistence (63.5%). Polypharmacy (47.1%) was not associated with non-adherence. Total stay was 1,527 days (mean stay was 14.7 (SD 14.0) days/episode): psychiatry 827 days (54.2%); cardiology 174 days (11.4%); critical unit 48 days (3.1%). Patients with a degree of adherence <= 75% had a mean stay/episode higher than those with a degree of adherence > 75%, without significant differences (p > 0.05, t-Student). Overall cost of hospitalization was Euros 594,230.8, with a mean cost/episode: Euros 5,713.6 (SD 5,039.5). Mean cost/episode for adherence <= 75% was higher than > 75%, Euros 6,275.8 (SD 5,526.2) vs Euros 3,895.6 (SD 2,371.3), (p < 0.05, t Student). CONCLUSIONS: The profile of this patient is fundamentally, a male psychiatric or chronic cardiac patient with a degree of adherence <= 75% due to abandoning domiciliary treatment. Admissions due to medication non-adherence are associated with an important depletion of economic resources in the hospital. PMID- 25137167 TI - [Toward a new model of pharmacy management comprehensive care of patients with chronic kidney disease]. AB - OBJECTIVE: The treatment of chronic kidney disease represents 2.5% of the National Healthcare System budget. Given the panorama of economic crisis, actions aimed at containing the costs in this kind of pathologies should be implemented. METHOD: Centralization of the management of the medications used for the treatment of chronic kidney disease and its complications aims at reducing the pharmaceutical expenditure. RESULTS: The new contracts of public healthcare administrations with companies of dialysis centers establish a single price by which the contractor takes care of the integral management of the patients, including the dialysis therapy and pharmacological treatment. Drug management at dialysis centers will be handled by specialized pharmacists by means of the creation of pharmacy departments or drug warehouse. CONCLUSIONS: these measures aim at improving healthcare of the patient in hemodialysis program, with health benefits at a lower healthcare cost. PMID- 25137165 TI - [Cost-effectiveness analysis of aflibercept in combination with FOLFIRI in the treatment of patients with metastatic colorectal cancer]. AB - OBJECTIVES: To estimate the incremental cost per life-year gained (LYG) of aflibercept in combination with FOLFIRI as second-line treatment in metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. METHODS: Based on clinical trial VELOUR results, a three-state Markov model (stable disease, progression and death) with 2-week cycle duration was designed. Transition to health state "progression" implied the interruption of second-line treatment and administration of a third-line treatment (post-second line chemotherapy). Cost estimation included disease management cost (pharmaceutical, adverse event management, administration costs, etc.). Both cost and outcomes were discounted (3% annually). Sensitivity analyses (SA) were performed to test model robustness. RESULTS: Administration of aflibercept + FOLFIRI as second-line treatment provided 1.78 LYG (21 life-months gained). With FOLFIRI 1.43 LYG (17 months) were obtained. The cost of the clinical management of aflibercept + FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros 38,346, compared to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI. CONCLUSION: Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy in the treatment of patients with mCRC. Aflibercept in combination with FOLFIRI is an efficient strategy for second-line mCRC treatment from the National Health System perspective. PMID- 25137168 TI - [Review of pharmacological interactions of oral anticancer drugs provided at pharmacy department]. AB - OBJECTIVE: To identify the pharmacologic interactions of oral anti-cancer drugs provided at an outpatient clinic. MATERIAL AND METHODS: Anti-cancer drugs included in the Phamacotherapeutic Guideline of the Hospital were identified. A literature search was carried out on the pharmacologic interactions in MEDLINE(r) and EMBASE(r) (with the filer language English or Spanish, and the descriptors: "name of the anti-cancer drug" AND ("drug interactions" OR "pharmacokinetic")), Up-to-date(r), MICROMEDEX(r) and the drug information sheet for the EMA and the FDA. Information was also gathered from the abstract presented to European and Spanish scientific meetings for the last 4 years. When an interaction was analyzed and had clinical relevance, the best pharmacotherapeutic interaction free alternative was sought. RESULTS: Twenty-three drugs were identified, of which Chlorambucil, Fludarabine, Lenalidomide, Melphalan, and Thalidomide were the active compounds with the lowest likelihood of producing a pharmacologic interaction. Tyrosine kinase inhibitors (particularly Erlotinib, Imatinib, Lapatinib, and Pazopanib) are the drugs with highest number of pharmacologic interactions described, many of them with severe clinical consequences, with increases and decreases of the plasma levels of anti-cancer drugs. The active compounds identified that may have pharmacologic interactions with anticancer drugs were mainly: Allopurinol, Amiodarone, Carbamazepine, Dabigatran, Digoxin, Spironolactone, Phenytoin, Itraconazol, Repaglinide, Silodosin, Tamoxifen, Verapamil, and Warfarin. Pharmacologic interactions through the cytochrome P450 1A2, 2D6, 2C8, 2C9, 3A4 were the most important for tyrosine kinase inhibitors. Other non-pharmacologic compounds, with an important potential of producing relevant pharmacologic interaction were immunomodulators (Echinacea extracts) and Hypericum perforatum. CONCLUSIONS: Oral anticancer drugs have numerous pharmacologic interactions that should be monitored during pharmacotherapy. Given its position, the hospital pharmacist is the key professional for identifying and assessing the pharmacologic interactions or oral anticancer drugs that may have clinical consequences. PMID- 25137169 TI - [An update in drug use during pregnancy: risk classification]. AB - OBJECTIVE: To review medicines pregnancy category and establish the degree of conformity between the two systems more used: FDA (Food and Drug Administration) and ACPM (advisory Committee on Prescription Medicines). METHODS: drugs used in most frequent pathologies during pregnancy have been selected and found its pregnancy category according to FDA and ACPM. The degree of conformity has been established between both categorisation systems. RESULTS: a total of 270 medicines were reviewed. 260 drugs had pregnancy category by FDA and 245 by ACPM system. 232 drugs had pregnancy category defined by both classifications (FDA and ACPM). We found 70,2% of them in the same pregnancy category. CONCLUSIONS: The discrepancies found in both pregnancy categorisation systems can be confused in order to prescribe and know its safety statement of medicines during pregnancy which can limits its utility. It would be desirable more studies after medicines registered to get more information which could help to use safety drugs during pregnancy and minimize discrepancies between both pregnancy categorisation systems. PMID- 25137170 TI - [Treatment with urea as an alternative to tolvaptan for the syndrome of inappropriate secretion of antidiuretic hormone]. PMID- 25137171 TI - [Are scientific literature databases a good source of scientific evidence for discontinuing a drug from the market?]. PMID- 25137172 TI - [Systemic absorption of oral vancomycin in colitis patients. A propos of 2 cases]. PMID- 25137173 TI - [Management of systemic idiopathic juvenile arthritis in pediatrics with biological agents: a propos of a case]. PMID- 25137174 TI - [Intralesional rituximab in ocular adnexal lymphoma]. PMID- 25137175 TI - Climatic niche conservatism and biogeographical non-equilibrium in Eschscholzia californica (Papaveraceae), an invasive plant in the Chilean Mediterranean region. AB - Species climate requirements are useful for predicting their geographic distribution. It is often assumed that the niche requirements for invasive plants are conserved during invasion, especially when the invaded regions share similar climate conditions. California and central Chile have a remarkable degree of convergence in their vegetation structure, and a similar Mediterranean climate. Such similarities make these geographic areas an interesting natural experiment for testing climatic niche dynamics and the equilibrium of invasive species in a new environment. We tested to see if the climatic niche of Eschscholzia californica is conserved in the invaded range (central Chile), and we assessed whether the invasion process has reached a biogeographical equilibrium, i.e., occupy all the suitable geographic locations that have suitable conditions under native niche requirements. We compared the climatic niche in the native and invaded ranges as well as the projected potential geographic distribution in the invaded range. In order to compare climatic niches, we conducted a Principal Component Analysis (PCA) and Species Distribution Models (SDMs), to estimate E. californica's potential geographic distribution. We also used SDMs to predict altitudinal distribution limits in central Chile. Our results indicated that the climatic niche occupied by E. californica in the invaded range is firmly conserved, occupying a subset of the native climatic niche but leaving a substantial fraction of it unfilled. Comparisons of projected SDMs for central Chile indicate a similarity, yet the projection from native range predicted a larger geographic distribution in central Chile compared to the prediction of the model constructed for central Chile. The projected niche occupancy profile from California predicted a higher mean elevation than that projected from central Chile. We concluded that the invasion process of E. californica in central Chile is consistent with climatic niche conservatism but there is potential for further expansion in Chile. PMID- 25137176 TI - An efficient and highly versatile synthetic route to prepare iron oxide nanoparticles/nanocomposites with tunable morphologies. AB - We report a versatile synthetic method for the in situ self-assembly of magnetic nanoparticle-functionalized polymeric nanomorphologies, including spherical micelles and rod-like and worm-like micelles and vesicles. Poly(oligoethylene glycol methacrylate)-block-(methacrylic acid)-block-poly(styrene) (POEGMA-b-PMAA b-PST) triblock copolymer chains were simultaneously propagated and self assembled via a polymerization-induced self-assembly (PISA) approach. Subsequently, the carboxylic acid groups in the copolymers were used to complex an iron ion (Fe(II)/Fe(III)) mixture. Iron oxide nanoparticles were then formed in the central block, within the polymeric nanoparticles, via alkaline coprecipitation of the iron(II) and (III) salts. Nanoparticle morphologies, particle sizes, molecular weights, and chemical structures were then characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), size exclusion chromatography (SEC), and (1)H NMR measurements. TEM micrographs showed that the average size of the magnetic nanoparticles was ~7 nm at the hydrophobic/hydrophilic nexus contained within the nanoparticles. In addition, XRD was used to confirm the formation of iron oxide nanoparticles. Importantly, the polymeric nanoparticle morphologies were not affected by the coprecipitation of the magnetic nanoparticles. The hybrid nanoparticles were then evaluated as negative MRI contrast agents, displaying remarkably high transverse relaxivities (r2, greater than 550 mM(-1) s(-1) at 9.4 T); a result, that we hypothesize, ensues from iron oxide nanoparticle clustering at the hydrophobic hydrophilic interface. This simple synthetic procedure is highly versatile and produces nanocarriers of tunable size and shape with high efficacy as MRI contrast agents and potential utility as theranostic delivery vectors. PMID- 25137177 TI - A novel HoxB cluster protein expressed in the hindbrain and pharyngeal arches. AB - We describe a novel zebrafish line that fluorescently tags a previously unknown protein, CT74a, allowing us to follow its endogenous expression in real time and at subcellular resolution in live embryos. Our results showed that CT74a-Citrine fusion protein is expressed in the developing pharyngeal arches, hindbrain, and fin buds in a pattern highly reminiscent of transcription factors belonging to anterior Hox gene families, including expression in a subset of neuronal nuclei. Consistent with this, splinkerette-PCR revealed that CT74a-Citrine's genomic integration is within the HoxB region, and 3' RACE demonstrated that its downstream coding sequence has no recognizable homology. Thus, CT74a is a previously unknown protein located within the HoxB cluster adjacent to Hoxb4a and is expressed in a Hoxb4a-like pattern. PMID- 25137178 TI - LM and TEM study of the orthokeratinized and parakeratinized epithelium of the tongue in the domestic duck (Anas platyrhynchos f. domestica). AB - The previous histological studies of the lingual mucosa in birds characterized two types of keratinized epithelium, i.e. orthokeratinized and parakeratinized. These epithelia are composed of three layers: basal, intermediate and keratinized. The present study showed detailed ultrastructural features of cells in particular layers of two types of keratinized epithelia on the tongue in the domestic duck and defined structural differences. TEM observations showed a gradual reduction in cell organelles in the following layers, at increasing amounts of keratin fibers. The characteristic feature of the ortho- and parakeratinized epithelium is the presence of sub-layers in the intermediate layer, i.e. the upper and lower part, which results from the different shape of cell nuclei and dye affinity of the cytoplasm. The keratinized layer of ortho- and parakeratinized epithelium is built of two types of cells such as electron dark and light cells, which undergo exfoliation. The basic difference between the keratinized epithelia is the presence of flattened cell nuclei in the keratinized layer of the parakeratinized epithelium. The differentiating feature is also an arrangement of keratin fibers in the cell cytoplasm of the keratinized layer. The analysis of the thickness of the epithelium and the keratinized layer, indicated differences between keratinized epithelia, which result from two variants of performing protective functions, either through a thick keratinized layer or by a higher epithelium. Differences in the ultrastructure of the ortho- and parakeratinized epithelium are associated with mechanical functions of the epithelium resulting from different forces acting on the tongue during feeding activities. PMID- 25137179 TI - Targeted theranostic prodrugs based on an aggregation-induced emission (AIE) luminogen for real-time dual-drug tracking. AB - A targeted theranostic delivery system containing two prodrugs with drug tracking and activation monitoring functions was developed for visualizing cancer cell ablation with synergistic anticancer effects. PMID- 25137180 TI - The influence of Chinese one-child family status on developmental coordination disorder status. AB - We conducted a population-based study on Developmental Coordination Disorder (DCD) in mainland China to explore the influence of one-child status in Chinese families on DCD. A total of 4001 children selected from 160 classes in 15 public nursery schools. The Movement Assessment Battery for Children assessed motor function. The prevalence of DCD in Chinese one-child families (8.7%) was higher than that in multi-child families (5.9%). Chinese one-child family status (compared with younger children in multi-child families) were negatively related with total score (-1.793), Manual dexterity (-0.228), Aiming and catching ( 1.145), Balance (-0.433) of MABC-2 and DCD (OR=2.294) when adjusted for the children's and family's characteristics, and perinatal factors (each p<0.05). As one of the studies in this Chinese context, it provides a platform for future intervention programs in one-child families in preventing children's developmental disorders. PMID- 25137182 TI - Yoga: a biobehavioral approach to reduce symptom distress in women with urge urinary incontinence. AB - Urge urinary incontinence is a debilitating chronic condition that poses challenges for affected women and the clinicians who care for them. Multicomponent behavioral therapies have shown promise in allowing women to manage their symptoms. New evidence suggests an underlying pathophysiologic inflammatory process for urge urinary incontinence, and complementary therapies that address the psychoneuroimmunology component may improve the health and quality of life for the millions of women with this condition. Yoga, a mind-body therapy, has been shown to reduce inflammation and may help improve symptoms of urge urinary incontinence. More research is necessary to demonstrate the effectiveness of yoga to reduce urge urinary incontinence symptom burden and improve quality of life. PMID- 25137181 TI - Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC patients by next generation sequencing: toward a real-time liquid biopsy for treatment. AB - INTRODUCTION: Assessment of EGFR mutation in non-small cell lung cancer (NSCLC) patients is mandatory for optimization of pharmacologic treatment. In this respect, mutation analysis of circulating tumor cells (CTCs) may be desirable since they may provide real-time information on patient's disease status. EXPERIMENTAL DESIGN: Blood samples were collected from 37 patients enrolled in the TRIGGER study, a prospective phase II multi-center trial of erlotinib treatment in advanced NSCLC patients with activating EGFR mutations in tumor tissue. 10 CTC preparations from breast cancer patients without EGFR mutations in their primary tumors and 12 blood samples from healthy subjects were analyzed as negative controls. CTC preparations, obtained by the Veridex CellSearch System, were subjected to ultra-deep next generation sequencing (NGS) on the Roche 454 GS junior platform. RESULTS: CTCs fulfilling all Veridex criteria were present in 41% of the patients examined, ranging in number between 1 and 29. In addition to validated CTCs, potential neoplastic elements were seen in 33 cases. These included cells not fulfilling all Veridex criteria (also known as "suspicious objects") found in 5 (13%) of 37 cases, and isolated or clustered large naked nuclei with irregular shape observed in 33 (89%) cases. EGFR mutations were identified by NGS in CTC preparations of 31 (84%) patients, corresponding to those present in matching tumor tissue. Twenty-five (96%) of 26 deletions at exon 19 and 6 (55%) of 11 mutations at exon 21 were detectable (P = 0.005). In 4 (13%) cases, multiple EGFR mutations, suggesting CTC heterogeneity, were documented. No mutations were found in control samples. CONCLUSIONS: We report for the first time that the CellSearch System coupled with NGS is a very sensitive and specific diagnostic tool for EGFR mutation analysis in CTC preparations with potential clinical impact. PMID- 25137183 TI - Physical exercise restores microvascular function in obese rats with metabolic syndrome. AB - BACKGROUND: Obesity and metabolic syndrome are related to systemic functional microvascular alterations, including a significant reduction in microvessel density. The aim of this study was to investigate the effects of exercise training on functional capillary density in the skeletal muscle and skin of obese rats with metabolic syndrome. METHODS: We used male Wistar-Kyoto rats that had been fed a standard commercial diet (CON) or high-fat diet (HFD) for 32 weeks. Animals receiving the HFD were randomly divided into sedentary (HFD+SED) and training groups (HFD+TR) at the 20(th) week. After 12 weeks of aerobic treadmill training, the maximal oxygen uptake (VO2max); hemodynamic, biochemical, and anthropometric parameters; and functional capillary density were assessed. In addition, a maximal exercise test was performed. RESULTS: Exercise training increased the VO2max (69 +/- 3 mL/kg per min) and exercise tolerance (30 +/- 1 min) compared with the HFD+SED (41 +/- 6 mL/kg per min, P < 0.05 and 16 +/- 1 min, P < 0.001) and with the CON (52 +/- 7 mL/kg per min and 18 +/- 1 min, P < 0.05) groups. The HFD+TR group also showed reduced retroperitoneal fat (0.03 +/- 0.00 vs. 0.05 +/- 0.00 gram/gram, P < 0.001), epididymal fat (0.01 +/- 0.00 vs. 0.02 +/- 0.00 gram/gram, P < 0.001), and systolic blood pressure (127 +/- 2 vs. 150 +/- 2 mmHg, P<0.001). The HFD+TR group also demonstrated improved glucose tolerance, as evaluated by an intraperitoneal glucose tolerance test, fasting plasma glucose levels (5.0 +/- 0.1 vs. 6.4 +/- 0.2 mmol/L, P<0.001) and fasting plasma insulin levels (26.5 +/- 2.3 vs. 38.9 +/- 3.7 MUIU/mL, P < 0.05). Glucose tolerance did not differ between HFD+TR and CON groups. Exercise training also increased the number of spontaneously perfused capillaries in the skeletal muscle (252 +/- 9 vs. 207 +/- 9 capillaries/mm(2)) of the training group compared with that in the sedentary animals (260 +/- 15 capillaries/mm(2)). CONCLUSIONS: These results demonstrate that exercise training reverses capillary rarefaction in our experimental model of metabolic syndrome and obesity. PMID- 25137185 TI - Delay in seeking medical help following Transient Ischemic Attack (TIA) or "mini stroke": a qualitative study. AB - BACKGROUND: Prompt treatment following Transient Ischemic Attack (TIA) can reduce the risk of subsequent stroke and disability. However, many patients delay in making contact with medical services. This study aimed to explore TIA patients' accounts of delay between symptom onset and contacting medical services including how decisions to contact services were made and the factors discussed in relation to delay. METHODS: Twenty interviews were conducted with TIA patients in England. Using a previous systematic review as an initial framework, interview data were organised into categories of symptom recognition, presence of others and type of care sought. A thematic analysis was then conducted to explore descriptions of care-seeking relevant to each category. RESULTS: Delay in contacting medical services varied from less than an hour to eight days. Awareness of typical stroke symptoms could lead to urgent action when more severe TIA symptoms were present but could lead to delay when experienced symptoms were less severe. The role of friends and family varied widely from deciding on and enacting care-seeking decisions to simply providing transport to the GP practice. When family or friends played a greater role, and both made and enacted care-seeking decisions, delays were often shorter, even when patients themselves failed to identify symptoms. Healthcare professionals also impacted on patients' care-seeking with greater delays in seeking further care for the same episode described when patients perceived a lack of urgency during initial healthcare interactions. CONCLUSIONS: This study provides new information on patients' decisions to contact medical services following TIA and identifies overlapping factors that can lead to delay in receiving appropriate treatment. While recognition of symptoms may contribute to delay in contacting medical services, additional factors, including full responsibility being taken by others and initial healthcare interactions, can over-ride or undermine the importance of patients' own identification of TIA. PMID- 25137187 TI - From the Editor-in-Chief's Desk. PMID- 25137186 TI - CTAG-containing cleavage site profiling to delineate Salmonella into natural clusters. AB - BACKGROUND: The bacterial genus Salmonella contains thousands of serotypes that infect humans or other hosts, causing mild gastroenteritis to potentially fatal systemic infections in humans. Pathogenically distinct Salmonella serotypes have been classified as individual species or as serological variants of merely one or two species, causing considerable confusion in both research and clinical settings. This situation reflects a long unanswered question regarding whether the Salmonella serotypes exist as discrete genetic clusters (natural species) of organisms or as phenotypic (e.g. pathogenic) variants of a single (or two) natural species with a continuous spectrum of genetic divergence among them. Our recent work, based on genomic sequence divergence analysis, has demonstrated that genetic boundaries exist among Salmonella serotypes, circumscribing them into clear-cut genetic clusters of bacteria. METHODOLOGIES/PRINCIPAL FINDINGS: To further test the genetic boundary concept for delineating Salmonella into clearly defined natural lineages (e.g., species), we sampled a small subset of conserved genomic DNA sequences, i.e., the endonuclease cleavage sites that contain the highly conserved CTAG sequence such as TCTAGA for XbaI. We found that the CTAG containing cleavage sequence profiles could be used to resolve the genetic boundaries as reliably and efficiently as whole genome sequence comparisons but with enormously reduced requirements for time and resources. CONCLUSIONS: Profiling of CTAG sequence subsets reflects genetic boundaries among Salmonella lineages and can delineate these bacteria into discrete natural clusters. PMID- 25137189 TI - Lurasidone treatment in a child with autism spectrum disorder with irritability and aggression. PMID- 25137188 TI - Childhood depression subscales using repeated sessions on Children's Depression Rating Scale - revised (CDRS-R) scores. AB - BACKGROUND: Although acute treatments have been shown to be effective in treating early-onset depression, only one-third or thereabouts reach a remission within 3 months. Unfortunately, delayed time to remission in early-onset depression leads to poorer therapeutic outcomes. Clearly, there is a need to identify, diagnose, and provide effective treatment of a depressed patient quickly. A sophisticated understanding of depression subscales and their change over time with treatment could enhance pathways to individualized treatment approaches for childhood depression. OBJECTIVE: Previous studies have found that the clinician-measured instrument, Children's Depression Rating Scale-Revised (CDRS-R) measures multiple subscales (or components) of depression. The aim of this study was to see how these subscales may change over the course of a 12-week study. This knowledge will help determine if dimensions/subscales of childhood depression (paralleling the adult literature) using the subscales derived from factor analysis procedure is useful. METHODS: We examined two clinical trials in which youth (n=234) with major depressive disorder (MDD) were treated openly with fluoxetine for eight sessions spread over 12 weeks. The CDRS-R was completed based on clinician interviews with parent and child at each session. Classical test theory and component analysis with associated parallel analysis (oblique rotation) were conducted on each week's scores. RESULTS: Although more factors were needed for the baseline and first two therapy sessions, a two-factor solution sufficed thereafter. Depressed facial affect, listless speech, and hypoactivity best defined Factor I, whereas sleep problems, appetite disturbance, physical symptoms, irritability, guilt, and weeping best defined Factor II. All other symptoms cross-loaded almost equally on the two factors. The scale's reliability (internal consistency) improved from baseline to exit sessions (alpha=0.65-0.91). As a result, the clinicians' assessments of the various symptoms became more highly related to one another. This caused the first eigenvalue to increase from 3.24 to 7.38 and the variance explained to increase (%) from 19% to 43% over sessions. These two factors may reflect 1) clinician-observed signs and 2) reported symptoms of depression. CONCLUSIONS: Factor analysis of CDRS-R data in a single session consistently generates a complex and difficult to interpret structure of at least three factors. This makes it very difficult to understand what these factors measure. However, when gathered over additional sessions, the CDRS-R structure tends to simplify to two factors. The reasons for this simplification are as yet unclear and in need of further study. PMID- 25137192 TI - Monitoring cellular stress responses using integrated high-frequency impedance spectroscopy and time-resolved ELISA. AB - We have developed a lab-on-a-chip system for continuous and non-invasive monitoring of microfluidic cell cultures using integrated high-frequency contactless impedance spectroscopy. Electrically insulated microfabricated interdigitated electrode structures were embedded into four individually addressable microchambers to reliably and reproducibly detect cell-substrate interactions, cell viability and metabolic activity. While silicon nitride passivated sensor substrates provided a homogeneous cell culture surface that minimized cell orientation along interdigitated electrode structures, the application of high-frequency AC fields reduced the impact of the 300 nm thick passivation layer on sensor sensitivity. The additional implementation of multivariate data analysis methods such as partial least square (PLS) for high frequency impedance spectra provided unambiguous information on intracellular pathway activation, up and down-regulation of protein synthesis as well as global cellular stress responses. A comparative cell analysis using connective tissue fibroblasts showed that high-frequency contactless impedance spectroscopy and time-resolved quantification of IL-6 secretion using ELISA provided similar results following stimulation with circulating pro-inflammatory cytokines IL 1beta and TNFalpha. The combination of microfluidics with contactless impedance sensing and time-resolved quantification of stress factor release will provide biologist with a new tool to (a) establish a variety of uniform cell culture surfaces that feature complex biochemistries, micro- and nanopatterns; and (b) to simultaneously characterize cell responses under physiologically relevant conditions using a complementary non-invasive cell analysis method. PMID- 25137193 TI - Sequence specific detection of restriction enzymes at DNA-modified carbon nanotube field effect transistors. AB - Protein-DNA interactions play a central role in many cellular processes, and their misregulation has been implicated in a number of human diseases. Thus, there is a pressing need for the development of analytical strategies for interrogating the binding of proteins to DNA. Herein, we report the electrical monitoring of a prototypical DNA-binding protein, the PvuII restriction enzyme, at microfluidic-encapsulated, DNA-modified carbon nanotube field effect transistors. Our integrated platform enables the sensitive, sequence specific detection of PvuII at concentrations as low as 0.5 pM in a volume of 0.025 MUL (corresponding to ~7500 proteins). These figures of merit compare favorably to state of the art values reported for alternative fluorescent and electrical assays. The overall detection strategy represents a step toward the massively parallel electrical monitoring, identification, and quantification of protein-DNA interactions at arrayed nanoscale devices. PMID- 25137194 TI - Plasmonic effects of au/ag bimetallic multispiked nanoparticles for photovoltaic applications. AB - In recent years, there has been considerable interest in the use of plasmons, that is, free electron oscillations in conductors, to boost the performance of both organic and inorganic thin film solar cells. This has been driven by the possibility of employing thin active layers in solar cells in order to reduce materials costs, and is enabled by significant advances in fabrication technology. The ability of surface plasmons in metallic nanostructures to guide and confine light in the nanometer scale has opened up new design possibilities for solar cell devices. Here, we report the synthesis and characterization of highly monodisperse, reasonably stable, multipode Au/Ag bimetallic nanostructures using an inorganic additive as a ligand for photovoltaic applications. A promising surface enhanced Raman scattering (SERS) effect has been observed for the synthesized bimetallic Au/Ag multispiked nanoparticles, which compare favorably well with their Au and Ag spherical nanoparticle counterparts. The synthesized plasmonic nanostructures were incorporated on the rear surface of an ultrathin planar c-silicon/organic polymer hybrid solar cell, and the overall effect on photovoltaic performance was investigated. A promising enhancement in solar cell performance parameters, including both the open circuit voltage (VOC) and short circuit current density (JSC), has been observed by employing the aforementioned bimetallic multispiked nanoparticles on the rear surface of solar cell devices. A power conversion efficiency (PCE) value as high as 7.70% has been measured in a hybrid device with Au/Ag multispiked nanoparticles on the rear surface of an ultrathin, crystalline silicon (c-Si) membrane (~ 12 MUm). This value compares well to the measured PCE value of 6.72% for a similar device without nanoparticles. The experimental observations support the hope for a sizable PCE increase, due to plasmon effects, in thin-film, c-Si solar cells in the near future. PMID- 25137195 TI - Feasibility of ballistic strengthening exercises in neurologic rehabilitation. AB - Conventional methods for strength training in neurologic rehabilitation are not task specific for walking. Ballistic strength training was developed to improve the functional transfer of strength training; however, no research has investigated this in neurologic populations. The aim of this pilot study was to evaluate the feasibility of applying ballistic principles to conventional leg strengthening exercises in individuals with mobility limitations as a result of neurologic injuries. Eleven individuals with neurologic injuries completed seated and reclined leg press using conventional and ballistic techniques. A 2 * 2 repeated-measures analysis of variance was used to compare power measures (peak movement height and peak velocity) between exercises and conditions. Peak jump velocity and peak jump height were greater when using the ballistic jump technique rather than the conventional concentric technique (P < 0.01). These findings suggest that when compared with conventional strengthening exercises, the incorporation of ballistic principles was associated with increased peak height and peak velocities. PMID- 25137197 TI - The World Health Organization disability action plan. PMID- 25137196 TI - Contralateral lumbar radicular pain shortly after a transforaminal epidural steroid injection: an unusual sequel. PMID- 25137198 TI - [Anesthesiologists teach teachers, teachers train students, students are lifesavers!]. PMID- 25137200 TI - [Case report: Aneurysmatic subarachnoid hemorrhage -- complicated course due to coincidental manifestation of an inverted Tako-Tsubo-cardiomyopathy]. AB - We report the case of a patient who suffered a serious subarachnoid hemorrhage with a cardialaffection and development of an inverted Tako-Tsubo-cardiomyopathy. To avoid apparent cerebral ischemia due to severe cerebral vasospasm after exhaustion of conservative therapeutic options a temporarily endovascular therapy with continuous intra-arterial application of Nimodipine was necessary. In the overall protracted and complicated course the special challenge were the therapeutic efforts to avoid apparent cerebral ischemia in context to the significant cardial affection. PMID- 25137201 TI - [Subsyndromal delirium -- experience in psychiatry -- expectations for postoperative management]. AB - The phenomenon of delirium is well known since over 100 years. The anesthesiology has recognized that early detection and therapy results in significant improvement of postoperative clinical state of health of the patients. In the following article it will be discussed that it could be profitable to make a further step: threatening the subsyndromal delirium. Because there are only few experiences in anesthesiology, this thesis will be substantiated by datas from psychiatry. PMID- 25137202 TI - [Resuscitation between the guidelines -- what has happened since 2010]. AB - The standards of treatment of patients suffering cardiac arrest is defined by international guidelines for cardiopulmonary resuscitation, that are updated every five years. Scientific knowledge is continuously increasing and recent studies should be considered and discussed to improve the results of daily emergency care. There are some leading topics of the ongoing discussion concerning airwaymanagement, mechanical ventilation, mechanical cpr-devices and extracorporal life support. The strategies of postresuscitation care are also in the focus of interest. This review presents and discusses the value of recent investigations on resuscitation science. PMID- 25137203 TI - [Patient safety -- mission for the future: Anesthesia -- but sure!]. PMID- 25137204 TI - [Patient safety -- mission for the future: Managing complications: what do I tell to the patients and what to the relatives?]. AB - In cases of unintended treatment courses an adequate communication is mandatory. Empathetic conversations expressing human warmth can pave the way to the avoidance of forensic consequences. The laws on patient's rights obligate the responsible physician to inform on request the patient about all recognizable circumstances that may lead to the assumption of a treatment error and to avoid hazards to health. The patient has a right to view his or her complete patient records and to demand that copy be made at the patient's expense. In the case of information to relatives the physician must observe the content and scope of his/her obligation to medical confidentiality. PMID- 25137205 TI - [Patient safety -- mission for the future: Recommendations for the management of severe treatment complications and burdensome courses (preventing the "second victim")]. AB - Avoiding complications is a major goal of all patient safety efforts. We are used to working with all kinds of algorithms for avoiding adverse events or for the diagnosis and treatment of possible unforeseen or inadvertent complications in our patients. As a matter of fact, severe complications certainly have an impact not only on the patient, but also on the medical team involved ("second victim"). Obviously there is no published standard in Germany on how to deal with this professional problem. Therefore, the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) has elaborated guidelines for the individual professional concerned, for the colleagues of doctors involved, as well as for the supervisors and hospital institutions. The aim of these recommendations is to encourage our professional society to set a focus on this problem and to offer a structured course of action for the case that a major complication occurs in spite of all our efforts to maintain our patient's safety. PMID- 25137206 TI - [Patient safety -- mission for the future: The importance of Critical Incident Reporting Systems (CIRS) in clinical practice]. AB - Every day patients experience harm due to errors and complications. To improve this situation, patient safety is increasingly becoming important in the treatment process. One aspect to increase patient safety is the Critical Incident Reporting System (CIRS). Observers and members of the care team are given the opportunity to anonymously report critical incidents and thus allow an analysis by an evaluation team. The goal is not to sanction the behavior of an individual, but to identify particular structural and organizational sources of error and to derive improvements. PMID- 25137207 TI - [Patient safety -- mission for the future: Healthcare-associated infections and antibiotic resistance]. AB - Healthcare-associated infections (HAI) are considered as one of the major challenges for modern health care. In the context of demographic change and the expected increase of invasive and complex patient treatment and concommittantrise in numbers of patients with underlying diseases with susceptibility to infections, quality of care and patient safety will in the near future depend strongly on the prevention of HAI. To avoid preventable HAI in terms of improved quality of care is beyond question, therefore mainly the prevalence of highly resistant microorganisms (HRMO) will becrucial for the success of treatment of unpreventable HAI. In addition to MRSA, the greatest danger in relation to antibiotic resistance worldwide are now considered tob e carbapenem-resistant Enterobacteriaceae (CRE) or multidrug-resistant Gram-negative (4MRGN) bacteria. In case oft he uncontrolled spread of HRMO unpreventable infections become also untreatable. The prevalence of HRMO varies between different countries. Especially in the Netherlands and Denmark HRMO such as MRSA, VRE and CRE/4MRGN are still significantly less common than in Germany or France. The reason lies in the fact that in nearly all Dutch hospitals anintegrative infectious disease service (clinical microbiology and/or infectious diseaseas wellinfection prevention) was established already years ago, while in Germany - with few exceptions - in most hospitals only a basic infectious disease services (consulting hygienist, microbiological diagnosis is held by laboratories often far away from the patient). As hospitals are connected with each other with respect to theircommon care of patients, one of the most important challenges in future infection prevention will be the implementation of regional and intersectoral infection prevention and control. PMID- 25137208 TI - [Scientific Update: ARDS and ECMO -- 4th ARDS/ECMO Symposium in Marburg]. PMID- 25137211 TI - Cardiac Transplants With Cyclosporin-A and Low-Dose Prednisone: Histologic Graduation of Rejection. PMID- 25137212 TI - Hydraphile synthetic ion channels alter root architecture in Arabidopsis thaliana. AB - The presence of low concentrations of hydraphile synthetic amphiphiles have been found to dramatically alter the primary/lateral root architectural balance in the A. thaliana plant model system and a correlation to ion transport by the hydraphiles is consistent with the effects. PMID- 25137213 TI - Dissolution, agglomerate morphology, and stability limits of protein-coated silver nanoparticles. AB - Little is understood regarding the impact that molecular coatings have on nanoparticle dissolution kinetics and agglomerate formation in a dilute nanoparticle dispersion. Dissolution and agglomeration processes compete in removing isolated nanoparticles from the dispersion, making quantitative time dependent measurements of the mechanisms of nanoparticle loss particularly challenging. In this article, we present in situ ultra-small-angle X-ray scattering (USAXS) results, simultaneously quantifying dissolution, agglomeration, and stability limits of silver nanoparticles (AgNPs) coated with bovine serum albumin (BSA) protein. When the BSA corona is disrupted, we find that the loss of silver from the nanoparticle core is well matched by a second order kinetic rate reaction, arising from the oxidative dissolution of silver. Dissolution and agglomeration are quantified, and morphological transitions throughout the process are qualified. By probing the BSA-AgNP suspension around its stability limits, we provide insight into the destabilization mechanism by which individual particles rapidly dissolve as a whole rather than undergo slow dissolution from the aqueous interface inward, once the BSA layer is breached. Because USAXS rapidly measures over the entire nanometer to micrometer size range during the dissolution process, many insights are also gained into the stabilization of NPs by protein and its ability to protect the labile metal core from the solution environment by prohibiting the diffusion of reactive species. This approach can be extended to a wide variety of coating molecules and reactive metal nanoparticle systems to carefully survey their stability limits, revealing the likely mechanisms of coating breakdown and ensuing reactions. PMID- 25137214 TI - High-performance ionic diode membrane for salinity gradient power generation. AB - Salinity difference between seawater and river water is a sustainable energy resource that catches eyes of the public and the investors in the background of energy crisis. To capture this energy, interdisciplinary efforts from chemistry, materials science, environmental science, and nanotechnology have been made to create efficient and economically viable energy conversion methods and materials. Beyond conventional membrane-based processes, technological breakthroughs in harvesting salinity gradient power from natural waters are expected to emerge from the novel fluidic transport phenomena on the nanoscale. A major challenge toward real-world applications is to extrapolate existing single-channel devices to macroscopic materials. Here, we report a membrane-scale nanofluidic device with asymmetric structure, chemical composition, and surface charge polarity, termed ionic diode membrane (IDM), for harvesting electric power from salinity gradient. The IDM comprises heterojunctions between mesoporous carbon (pore size ~7 nm, negatively charged) and macroporous alumina (pore size ~80 nm, positively charged). The meso-/macroporous membrane rectifies the ionic current with distinctly high ratio of ca. 450 and keeps on rectifying in high-concentration electrolytes, even in saturated solution. The selective and rectified ion transport furthermore sheds light on salinity-gradient power generation. By mixing artificial seawater and river water through the IDM, substantially high power density of up to 3.46 W/m(2) is discovered, which largely outperforms some commercial ion-exchange membranes. A theoretical model based on coupled Poisson and Nernst-Planck equations is established to quantitatively explain the experimental observations and get insights into the underlying mechanism. The macroscopic and asymmetric nanofluidic structure anticipates wide potentials for sustainable power generation, water purification, and desalination. PMID- 25137215 TI - Self-regulation and protective health behaviour: how regulatory focus and anticipated regret are related to vaccination decisions. AB - OBJECTIVE: We examined how individual motivational orientations and anticipated regret are related to the protective health decision of vaccination behaviour. DESIGN: The proposed relations were examined in a large-scale sample (N = 3168) and three medium-sized samples (N = 151, N = 194, N = 208). Questionnaires were applied to assess regulatory focus, anticipated regret and vaccination behaviour. RESULTS: Increased prevention-focused self-regulation - which is represented by concerns about security-related goals, responsibilities and obligations - was related to a greater likelihood of vaccination. Prevention-focused individuals' higher likelihood of getting vaccinated seems at least in part to be a consequence of anticipated regret for not vaccinating. Study 3 suggests that regulatory focus is less related to vaccination decisions when regret is increased by the decision-making context; that is, when information highlighting vaccination effectiveness and a low likelihood of adverse responses is provided. CONCLUSION: Prevention-focused self-regulation is related to a greater likelihood of engaging in health-protective behaviour. This can be explained by prevention focused individuals' greater tendency to anticipate regret about getting ill as a consequence of not adopting protective measures. If people perceive a protective measure such as a vaccination as highly effective, anticipated regret for not adopting it is generally increased, and individual differences in regulatory focus no longer predict the decision. PMID- 25137217 TI - Single-molecule-magnet behavior in the family of [Ln(OETAP)2] double-decker complexes (Ln=lanthanide, OETAP=octa(ethyl)tetraazaporphyrin). AB - Double-decker complexes of lanthanide cations can be readily prepared with tetraazaporphyrins (porphyrazines). We have synthesized and characterized a series of neutral double-decker complexes [Ln(OETAP)2 ] (Ln=Tb(3+), Dy(3+), Gd(3+), Y(3+); OETAP=octa(ethyl)tetraazaporphyrin). Some of these complexes show analogous magnetic features to their phthalocyanine (Pc) counterparts. The Tb(3+) and Dy(3+) derivatives exhibit single-molecule magnet (SMM) behavior with high blocking temperatures over 50 and 10 K, respectively. These results confirm that, in double-decker complexes that involve Tb or Dy, the (N4)2 square antiprism coordination mode has an important role in inducing very large activation energies for magnetization reversal. In contrast with their Pc counterparts, the use of tetraazaporphyrin ligands endows the presented [Ln(OETAP)2] complexes with extraordinary chemical versatility. The double-decker complexes that exhibit SMM behavior are highly soluble in common organic solvents, and easily processable even through sublimation. PMID- 25137216 TI - Replacing intrusive thoughts: investigating thought control in relation to OCD symptoms. AB - BACKGROUND AND OBJECTIVES: Control of obsessive thoughts in Obsessive Compulsive Disorder (OCD) involves both avoidance and removal of undesirable intrusive thoughts. Thought suppression tasks tap both of these processes but experimental results have been inconsistent. Experimental tasks allowing more focused study of the processes involved in controlling intrusive thoughts may be needed. In two experiments, control over neutral, standardized intrusive and personal intrusive thoughts was investigated as participants attempted to replace them with neutral thoughts. METHODS: Non-selected university students (Experiment 1: N = 61) and university students scoring high and low on self-report measure of OC symptoms (Experiment 2: N = 40) performed a computerized thought replacement task. RESULTS: In experiment 1 replacing personal intrusive thoughts took longer than replacing neutral thoughts. Self-reports showed that intrusive thoughts were rated more difficult to replace and were associated with greater thought reoccurrence during replacement, larger emotional reaction and more discomfort. These results were largely replicated in experiment 2. Furthermore, the high OC symptom group experienced greater overall difficulty controlling thoughts on the replacement task, experienced more reoccurrences of personal intrusive thoughts, larger emotional reactions and discomfort associated with them, and felt a greater urge to remove them. LIMITATIONS: All participants were non-clinical university students, and older adults with OCD should be tested. CONCLUSIONS: The findings are in line with cognitive behavioural theories of OCD. They support the usefulness of thought replacement as a research paradigm to study thought control in OCD and possibly other psychological conditions characterized by repetitive thoughts. PMID- 25137218 TI - Layered double hydroxide-based nanomaterials as highly efficient catalysts and adsorbents. AB - Layered double hydroxides (LDHs) are a class of anion clays consisting of brucite like host layers and interlayer anions, which have attracted increasing interest in the fields of catalysis/adsorption. By virtue of the versatility in composition, morphology, and architecture of LDH materials, as well as their unique structural properties (intercalation, topological transformation, and self assembly with other functional materials), LDHs display great potential in the design and fabrication of nanomaterials applied in photocatalysis, heterogeneous catalysis, and adsorption/separation processes. Taking advantage of the structural merits and various control synthesis strategies of LDHs, the active center structure (e.g., crystal facets, defects, geometric and electronic states, etc.) and macro-nano morphology can be facilely manipulated for specific catalytic/adsorbent processes with largely enhanced performances. In this review, the latest advancements in the design and preparation of LDH-based functional nanomaterials for sustainable development in catalysis and adsorption are summarized. PMID- 25137219 TI - Evidence that neurovascular coupling underlying the BOLD effect increases with age during childhood. AB - Functional MRI using blood-oxygen-level-dependent (BOLD) imaging has provided unprecedented insights into the maturation of the human brain. Task-based fMRI studies have shown BOLD signal increases with age during development (ages 5-18) for many cognitive domains such as language and executive function, while functional connectivity (resting-state) fMRI studies investigating regionally synchronous BOLD fluctuations have revealed a developing functional organization of the brain from a local into a more distributed architecture. However, interpretation of these results is confounded by the fact that the BOLD signal is directly related to blood oxygenation driven by changes in blood flow and only indirectly related to neuronal activity, and may thus be affected by changing neuronal-vascular coupling. BOLD signal and cerebral blood flow (CBF) were measured simultaneously in a cohort of 113 typically developing awake participants ages 3-18 performing a narrative comprehension task. Using a novel voxelwise wild bootstrap analysis technique, an increased ratio of BOLD signal to relative CBF signal change with age (indicative of increased neuronal-vascular coupling) was seen in the middle temporal gyri and the left inferior frontal gyrus. Additionally, evidence of decreased relative oxygen metabolism (indicative of decreased neuronal activity) with age was found in the same regions. These findings raise concern that results of developmental BOLD studies cannot be unambiguously attributed to neuronal activity. Astrocytes and astrocytic processes may significantly affect the maturing functional architecture of the brain, consistent with recent research demonstrating a key role for astrocytes in mediating increased CBF following neuronal activity and for astrocyte processes in modulating synaptic connectivity. PMID- 25137220 TI - Semiparametric adjusted exposure-response curves. AB - Exposure-response curves are central to understanding how continuous exposures relate to health outcomes. Common methods to plot such curves include the use of crude and adjusted regression, with the exposure specified using fractional polynomials or regression splines. These approaches are subject to important limitations. In this article, we illustrate the use of semiparametric marginally adjusted exposure-response curves obtained via inverse probability weighting. We explore the relation between interpregnancy interval and preterm birth in a cohort of over 720,000 live births in Quebec between 1989 and 2008. We include online supplementary material showing how mixed modeling routines in standard software packages can be used to implement the procedure, and how pointwise bootstrap confidence intervals can be obtained. PMID- 25137221 TI - Effectiveness of three different walking prescription durations on total physical activity in normal- and overweight women. AB - OBJECTIVE: While there is a dose-response relationship between physical activity (PA) and health benefit, little is known about the effectiveness of different PA prescriptions on total daily PA. AIM: To test, under real-life conditions and using an objective, non-invasive measurement technique (accelerometry), the effect of prescribing additional physical activity (walking only) of different durations (30, 60 and 90 min/day) on compliance (to the activity prescribed) and compensation (to total daily PA). Participants in each group were prescribed 5 sessions of walking per week over 4 weeks. METHODS: 55 normal-weight and overweight women (mean BMI 25 +/- 5 kg/m(2), height 165 +/- 1 cm, weight 68 +/- 2 kg and mean age 27 +/- 1 years) were randomly assigned to 3 prescription groups: 30, 60 or 90 min/day PA. RESULTS: Walking duration resulted in an almost linear increase in the number of steps per day during the prescription period from an average of about 10,000 steps per day for the 30-min prescription to about 14,000 for the 90-min prescription. Compliance was excellent for the 30-min prescription but decreased significantly with 60-min and 90-min prescriptions. In parallel, degree of compensation subsequent to exercise increased progressively as length of prescription increased. CONCLUSION: A 30-min prescription of extra walking 5 times per week was well tolerated. However, in order to increase total PA further, much more than 60 min of walking may need to be prescribed in the majority of individuals. While total exercise 'volume' increased with prescriptions longer than 30 min, compliance to the prescription decreased and greater compensation was evident. PMID- 25137222 TI - Squamous cell carcinoma of the skin (non-metastatic). AB - INTRODUCTION: Cutaneous squamous cell carcinoma is a malignant tumour of keratinocytes arising in the epidermis, with histological evidence of dermal invasion. Incidence varies by country, skin colour, and outdoor behaviour, and is as high as 400/100,000 in Australia. People with fair skin colour who have high sun exposure and sunburn easily with little or no tanning, people with xeroderma pigmentosum, and people who are immunosuppressed are most susceptible to squamous cell carcinoma. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: Does the use of sunscreen help prevent cutaneous squamous cell carcinoma and actinic (solar) keratosis? What is the optimal margin for primary excision of cutaneous squamous cell carcinoma (non metastatic)? Does radiotherapy after surgery affect local recurrence of cutaneous squamous cell carcinoma in people with squamous cell carcinoma of the skin (non metastatic)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2013 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found five studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: sunscreens, primary excision, and radiotherapy after surgery. PMID- 25137223 TI - Deposition of Particles in Human Mouth-Throat Replicas and a USP Induction Port. AB - BACKGROUND: Oral inhalation is the common route of drug delivery to pulmonary airways. In general, deposition in the oropharyngeal airways from a drug-delivery device makes up a substantial portion of the emitted dose, which affects the dose delivered to the lung. Studies with airway replicas made from cadaver or magnetic resonance imaging scans show that for micrometer-sized particles, impaction is the dominant deposition mechanism. Several deposition studies in oropharyngeal replicas found that the deposition efficiency can be correlated with the mouth inlet velocity and inlet mouthpiece diameter. Other studies show that the deposition efficiency is best correlated with the mean diameter of internal geometry and the mean velocity based on the mean diameter. METHOD: We investigated the mouth inlet diameter, as well as internal airway dimensions and their influence on oropharyngeal deposition based on experimental data from this study. Several human oropharyngeal replicas with different mouth inlet diameters and the USP induction port were used. RESULTS: We found that the aerosol deposition increased with decreasing mouth inlet diameter. Several mathematical expressions were tried to correlate the deposition efficiency with the Stokes number calculated based on (1) mouth inlet diameter and inlet velocity, (2) mean diameter of internal geometry and mean velocity, (3) mouth inlet velocity and mean diameter, and (4) mouth inlet velocity and minimum diameter in the oropharyngeal replica. The best correlation was obtained in case 4. CONCLUSIONS: This correlation could explain the intra-subject variation when deposition was found to vary with mouth inlet diameter, such as in some aerosol drug-delivery devices. It could also explain the intersubject variability in oropharyngeal deposition when human volunteers with different airway geometries and mouth openings were studied. PMID- 25137224 TI - Protective effects of escin against indomethacin-induced gastric ulcer in mice. AB - Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, is reported to have a potent antiulcer activity against ethanol induced gastric mucosal lesions. This study investigated the possible mechanisms underlying the gastroprotective effect of escin against indomethacin-induced gastric ulcer in mice. Gastric ulceration was induced by a single intragastric administration of indomethacin (18 mg/kg). The mice underwent intragastric treatment with escin at doses of 0.45, 0.9 or 1.8 mg/kg. Gastric lesion was estimated morphometrically and histopathologically 6 h after the indomethacin administration. The antioxidative parameters in gastric mucosa were measured. Moreover, the activity of myeloperoxidase and the contents of TNF-alpha, P selectin and VCAM-1 in gastric tissues were determined. The results showed that escin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from a reduction in the ulcer index and an attenuation of histopathologic changes. Escin caused significant reductions of the contents of malondialdehyde, TNF-alpha, P-selectin, VCAM-1 and myeloperoxidase activity. The altered activities of superoxide dismutase, catalase and glutathione peroxidase in the stomach tissues were also ameliorated by escin treatment. The present study demonstrated that escin had a protective effect against indomethacin induced gastric ulcer in mice, not only by virtue of its antioxidant potential, but also due to its anti-inflammatory effect. PMID- 25137228 TI - Spectroscopic study of jet-cooled deuterated porphycenes: unusual isotopic effects on proton tunneling. AB - Porphycene (Pc) is a well-known model for studying double hydrogen transfer, which shows vibrational-mode-specific tunneling splitting when isolated in supersonic jets or helium nanodroplets. The effect of deuteration on tunneling splitting is reported for jet-cooled heterogeneous, deuterated Pc samples (Pc d(mix)) with the prevailing contribution of Pc-d12 isotopologue. The sample introduced into the gas phase using laser desorption is studied by means of laser induced fluorescence (LIF) and single vibronic level fluorescence (SVLF) measurements, in combination with quantum chemical calculations. The influence of molecular symmetry is studied by comparing Pc, Pc-d12, and Pc-d11. The spectra of Pc-d12 show strong similarity to those of the parent undeuterated porphycene (Pc). Comparable tunneling splitting is observed in the two isotopologues, both for the 0-0 transition and the most efficient promoting 2Ag mode. In contrast, an unusual isotopic effect is observed for the totally symmetrical 4Ag mode. While this vibration behaves as a neutral mode in Pc, neither enhancing nor decreasing the tunneling efficiency, it strongly promotes hydrogen transfer in Pc-d12. This observation is explained in terms of modification of the displacement vectors of the 4Ag mode upon deuteration. It demonstrates that isotope substitution affects hydrogen transfer even when the weak structural modifications are far from the reaction center, emphasizing the strongly multidimensional nature of the tunneling process. PMID- 25137227 TI - Structural and functional investigation of zebrafish (Danio rerio) NOD1 leucine rich repeat domain and its interaction with iE-DAP. AB - Nucleotide binding and oligomerization domain 1 (NOD1), a cytoplasmic pattern recognition receptor (PRR) and is a key component for modulating innate immunity and signaling. It is highly specific to gamma-D-Glu-mDAP (iE-DAP), a cell wall component of Gram-negative and few Gram-positive bacteria. In the absence of the experimental structure of NOD1 leucine rich repeat (NOD1-LRR) domain, the NOD signaling cascade mediated through NOD1 and iE-DAP interaction is poorly understood. Herein, we modeled 3D structure of zebrafish NOD1-LRR (zNOD1-LRR) through a protein-threading approach and structural integrity of the model was assessed using molecular dynamics simulations. Molecular interaction analysis of iE-DAP and zNOD1-LRR, their complex stability and binding free energy studies were conducted to anticipate the ligand binding residues in zNOD1. Our study revealed that His775, Lys777, Asp803, Gly805, Trp807, Asn831, Ser833, Ile859 and Trp861 situated in the beta-sheet region of zNOD1-LRR could be involved in iE-DAP recognition, which correlates the earlier findings in human. Comparison of binding free energies of native and mutant zNOD1-iE-DAP complexes delineated His775, Lys777, Asp803, Ser833 and Ile859 as the pivotal residues for energetic stability of NOD1 and iE-DAP interaction. This study provides the first comprehensive description of biophysical and biochemical parameters responsible for NOD1 and iE-DAP interaction in zebrafish, which is expected to shed more light on NOD1 signaling and therapeutic applications in other organisms. PMID- 25137230 TI - Magnetic susceptibility of uranium complexes. PMID- 25137229 TI - Simple and validated quantitative 1H NMR method for the determination of methylation, acetylation, and feruloylation degree of pectin. AB - The knowledge of pectin esterification degree is of primary importance to predict gelling and other properties of pectin from different sources. This paper reports the development of a simple and rapid (1)H NMR-based method for the simultaneous quantitative determination of methylation, acetylation, and feruloylation degree of pectin isolated from various food sources. Pectin esters are hydrolyzed in NaOH/D2O, and the obtained methanol, acetic acid, and ferulic acid are directly measured by (1)H NMR. High accuracy, repeatability, and reproducibility of the method were obtained, and the analysis time is reduced as compared to conventional chromatography- or titration-based methods. PMID- 25137231 TI - Uncommon cis configuration of a metal-metal bridging noninnocent Nindigo ligand. AB - In contrast to several reported coordination compounds of trans-Nindigo ligands [Nindigo = indigo-bis(N-arylimine) = LH2] with one or two six-membered chelate rings involving one indole N and one extracyclic N for metal binding, the new diruthenium complex ion [(acac)2Ru(MU,eta(2):eta(2)-L)Ru(bpy)2](2+) = 2(2+) exhibits edge-sharing five- and seven-membered chelate rings in the first documented case of asymmetric bridging by a Nindigo ligand in the cis configuration [L(2-) = indigo-bis(N-phenylimine)dianion]. The dication in compound [2](ClO4)2 displays one Ru(alpha-diimine)3 site and one ruthenium center with three negatively charged chelate ligands. Compound [2](ClO4)2 is obtained from the [Ru(bpy)2](2+)-containing cis precursor [(LH)Ru(bpy)2]ClO4 = [1]ClO4, which exhibits intramolecular H-bonding in the cation. Four accessible oxidation states each were characterized for the 1(n) and 2(n) redox series with respect to metal- or ligand-centered electron transfer, based on X-ray structures, electron paramagnetic resonance, and ultraviolet-visible-near-infrared spectroelectrochemistry in conjunction with density functional theory calculation results. The structural asymmetry in the Ru(III)/Ru(II) system 2(2+) is reflected by the electronic asymmetry (class I mixed-valence situation), leaving the noninnocent Nindigo bridge as the main redox-active site. PMID- 25137225 TI - From pathways to networks: connecting dots by establishing protein-protein interaction networks in signaling pathways using affinity purification and mass spectrometry. AB - Signal transductions are the basis of biological activities in all living organisms. Studying the signaling pathways, especially under physiological conditions, has become one of the most important facets of modern biological research. During the last decade, MS has been used extensively in biological research and is proven to be effective in addressing important biological questions. Here, we review the current progress in the understanding of signaling networks using MS approaches. We will focus on studies of protein-protein interactions that use affinity purification followed by MS approach. We discuss obstacles to affinity purification, data processing, functional validation, and identification of transient interactions and provide potential solutions for pathway-specific proteomics analysis, which we hope one day will lead to a comprehensive understanding of signaling networks in humans. PMID- 25137234 TI - A multiple relevance feedback strategy with positive and negative models. AB - A commonly used strategy to improve search accuracy is through feedback techniques. Most existing work on feedback relies on positive information, and has been extensively studied in information retrieval. However, when a query topic is difficult and the results from the first-pass retrieval are very poor, it is impossible to extract enough useful terms from a few positive documents. Therefore, the positive feedback strategy is incapable to improve retrieval in this situation. Contrarily, there is a relatively large number of negative documents in the top of the result list, and it has been confirmed that negative feedback strategy is an important and useful way for adapting this scenario by several recent studies. In this paper, we consider a scenario when the search results are so poor that there are at most three relevant documents in the top twenty documents. Then, we conduct a novel study of multiple strategies for relevance feedback using both positive and negative examples from the first-pass retrieval to improve retrieval accuracy for such difficult queries. Experimental results on these TREC collections show that the proposed language model based multiple model feedback method which is generally more effective than both the baseline method and the methods using only positive or negative model. PMID- 25137233 TI - The roles of cellular nanomechanics in cancer. AB - The biomechanical properties of cells and tissues may be instrumental in increasing our understanding of cellular behavior and cellular manifestations of diseases such as cancer. Nanomechanical properties can offer clinical translation of therapies beyond what are currently employed. Nanomechanical properties, often measured by nanoindentation methods using atomic force microscopy, may identify morphological variations, cellular binding forces, and surface adhesion behaviors that efficiently differentiate normal cells and cancer cells. The aim of this review is to examine current research involving the general use of atomic force microscopy/nanoindentation in measuring cellular nanomechanics; various factors and instrumental conditions that influence the nanomechanical properties of cells; and implementation of nanoindentation methods to distinguish cancer cells from normal cells or tissues. Applying these fundamental nanomechanical properties to current discoveries in clinical treatment may result in greater efficiency in diagnosis, treatment, and prevention of cancer, which ultimately can change the lives of patients. PMID- 25137238 TI - Fumigant methyl iodide can methylate inorganic mercury species in natural waters. AB - Methyl iodide or iodomethane (CH3I) has recently been registered as a fumigant in many countries, although its environmental impacts are not well understood. Here we report the results of a study on the methylation of mercury by CH3I in natural water by incubation experiments using both Hg ((199)HgCl2 and CH3(201)Hg(+))- and hydrogen (CD3I)-stable isotope addition techniques. We find that methylation of Hg(0), Hg2(2+) and Hg(2+) by CH3I can occur in natural water under sunlight, while only Hg(0) and Hg2(2+) can be methylated in deionized water. We propose that the methylation of Hg by CH3I in natural waters is mediated by sunlight and involves two steps, the reduction of Hg(2+) to Hg(0)/Hg2(2+) and the subsequent methylation of Hg(0)/Hg2(2+) by CH3I. Further quantitative assessment suggests that CH3I-involved methylation of inorganic Hg could be an important source of CH3Hg(+) in an environment where CH3I has been used in large amounts as a fumigant. PMID- 25137235 TI - Effect of dialysis initiation timing on clinical outcomes: a propensity-matched analysis of a prospective cohort study in Korea. AB - BACKGROUND: Controversy persists regarding the appropriate initiation timing of renal replacement therapy for patients with end-stage renal disease. We evaluated the effect of dialysis initiation timing on clinical outcomes. Initiation times were classified according to glomerular filtration rate (GFR). METHODS: We enrolled a total of 1691 adult patients who started dialysis between August 2008 and March 2013 in a multi-center, prospective cohort study at the Clinical Research Center for End Stage Renal Disease in the Republic of Korea. The patients were classified into the early-start group or the late-start group according to the mean estimated GFR value, which was 7.37 ml/min/1.73 m2. The primary outcome was patient survival, and the secondary outcomes were hospitalization, cardiovascular events, vascular access complications, change of dialysis modality, and peritonitis. The two groups were compared before and after matching with propensity scores. RESULTS: Before propensity score matching, the early-start group had a poor survival rate (P<0.001). Hospitalization, cardiovascular events, vascular access complications, changes in dialysis modality, and peritonitis were not different between the groups. A total of 854 patients (427 in each group) were selected by propensity score matching. After matching, neither patient survival nor any of the other outcomes differed between groups. CONCLUSIONS: There was no clinical benefit after adjustment by propensity scores comparing early versus late initiation of dialysis. PMID- 25137239 TI - Transportation optimization with fuzzy trapezoidal numbers based on possibility theory. AB - In this paper, a parametric method is introduced to solve fuzzy transportation problem. Considering that parameters of transportation problem have uncertainties, this paper develops a generalized fuzzy transportation problem with fuzzy supply, demand and cost. For simplicity, these parameters are assumed to be fuzzy trapezoidal numbers. Based on possibility theory and consistent with decision-makers' subjectiveness and practical requirements, the fuzzy transportation problem is transformed to a crisp linear transportation problem by defuzzifying fuzzy constraints and objectives with application of fractile and modality approach. Finally, a numerical example is provided to exemplify the application of fuzzy transportation programming and to verify the validity of the proposed methods. PMID- 25137236 TI - Safety of hormonal replacement therapy and oral contraceptives in systemic lupus erythematosus: a systematic review and meta-analysis. AB - BACKGROUND: There is conflicting data regarding exogenous sex hormones [oral contraceptives (OC) and hormonal replacement therapy (HRT)] exposure and different outcomes on Systemic Lupus Erythematosus (SLE). The aim of this work is to determine, through a systematic review and meta-analysis the risks associated with estrogen use for women with SLE as well as the association of estrogen with developing SLE. METHODS AND FINDINGS: MEDLINE, EMBASE, SciElo, BIREME and the Cochrane library (1982 to July 2012), were databases from which were selected and reviewed (PRISMA guidelines) randomized controlled trials, cross-sectional, case control and prospective or retrospective nonrandomized, comparative studies without language restrictions. Those were evaluated by two investigators who extracted information on study characteristics, outcomes of interest, risk of bias and summarized strength of evidence. A total of 6,879 articles were identified; 20 full-text articles were included. Thirty-two meta-analyses were developed. A significant association between HRT exposure (Random model) and an increased risk of developing SLE was found (Rate Ratio: 1.96; 95%-CI: 1.51-2.56; P-value<0.001). One of eleven meta-analyses evaluating the risk for SLE associated with OC exposure had a marginally significant result. There were no associations between HRT or OC exposure and specific outcomes of SLE. It was not always possible to Meta-analyze all the available data. There was a wide heterogeneity of SLE outcome measurements and estrogen therapy administration. CONCLUSION: An association between HRT exposure and SLE causality was observed. No association was found when analyzing the risk for SLE among OC users, however since women with high disease activity/Thromboses or antiphospholipid-antibodies were excluded from most of the studies, caution should be exercised in interpreting the present results. To identify risk factors that predispose healthy individuals to the development of SLE who are planning to start HRT or OC is suggested. PMID- 25137240 TI - Gender and age-related differences in bilateral lower extremity mechanics during treadmill running. AB - Female runners have a two-fold risk of sustaining certain running-related injuries as compared to their male counterparts. Thus, a comprehensive understanding of the sex-related differences in running kinematics is necessary. However, previous studies have either used discrete time point variables and inferential statistics and/or relatively small subject numbers. Therefore, the first purpose of this study was to use a principal component analysis (PCA) method along with a support vector machine (SVM) classifier to examine the differences in running gait kinematics between female and male runners across a large sample of the running population as well as between two age-specific sub groups. Bilateral 3-dimensional lower extremity gait kinematic data were collected during treadmill running. Data were analysed on the complete sample (n = 483: female 263, male 220), a younger subject group (n = 56), and an older subject group (n = 51). The PC scores were first sorted by the percentage of variance explained and we also employed a novel approach wherein PCs were sorted based on between-gender statistical effect sizes. An SVM was used to determine if the sex and age conditions were separable and classifiable based on the PCA. Forty PCs explained 84.74% of the variance in the data and an SVM classification accuracy of 86.34% was found between female and male runners. Classification accuracies between genders for younger subjects were higher than a subgroup of older runners. The observed interactions between age and gender suggest these factors must be considered together when trying to create homogenous sub-groups for research purposes. PMID- 25137241 TI - Droplet electrospray ionization mass spectrometry for high throughput screening for enzyme inhibitors. AB - High throughput screening (HTS) is important for identifying molecules with desired properties. Mass spectrometry (MS) is potentially powerful for label-free HTS due to its high sensitivity, speed, and resolution. Segmented flow, where samples are manipulated as droplets separated by an immiscible fluid, is an intriguing format for high throughput MS because it can be used to reliably and precisely manipulate nanoliter volumes and can be directly coupled to electrospray ionization (ESI) MS for rapid analysis. In this study, we describe a "MS Plate Reader" that couples standard multiwell plate HTS workflow to droplet ESI-MS. The MS plate reader can reformat 3072 samples from eight 384-well plates into nanoliter droplets segmented by an immiscible oil at 4.5 samples/s and sequentially analyze them by MS at 2 samples/s. Using the system, a label-free screen for cathepsin B modulators against 1280 chemicals was completed in 45 min with a high Z-factor (>0.72) and no false positives (24 of 24 hits confirmed). The assay revealed 11 structures not previously linked to cathepsin inhibition. For even larger scale screening, reformatting and analysis could be conducted simultaneously, which would enable more than 145,000 samples to be analyzed in 1 day. PMID- 25137242 TI - Isotopic studies of the diet of the people of the coast of British Columbia. AB - In 1982, Chisholm et al. used delta(13) C data for human burials from shell midden sites widely distributed on the coast of British Columbia (BC) to show the extreme dependence of these individuals on high trophic level marine consumers, principally salmon and marine mammals. Here, we present previously unpublished analyses of delta(15) N for some of the same individuals as well as delta(13) C data for additional individuals. Nitrogen isotope data show that the diet was dominated by high trophic level marine fauna including carnivorous fish and marine mammals. Although most burials were found in shell middens, marine mollusks made up of only a minor component of diet. The data for delta(13) C demonstrate that terrestrial faunal foods are undetectable in the diet of the majority of individuals, and seldom constitute more than 10% of the dietary protein of individuals living on the coast although terrestrial fauna were widely available as a potential source of protein. This dietary pattern of exclusion of land-based animals from their diet persisted for almost 6,000 years along a wide expanse of coastline. In contrast, people from the BC interior (100 km or more from the coast) consumed a mixed diet of terrestrial and marine foods including spawning salmon. PMID- 25137244 TI - Sex-specific relationships of physical activity, body composition, and muscle quality with lower-extremity physical function in older men and women. AB - OBJECTIVE: This study aims to determine the sex-specific relationships of physical activity, body composition, and muscle quality with lower-extremity physical function in older men and women. METHODS: Seventy-nine community dwelling men (n = 39; mean [SD] age, 76.1 [6.2] y; mean [SD] body mass index, 27.3 [3.8] kg/m(2)) and women (n = 40; mean [SD] age, 75.8 [5.5] y; mean [SD] body mass index, 27.0 [3.8] kg/m(2)) were assessed for physical activity via questionnaire, body composition via dual-energy x-ray absorptiometry scanning, leg extension power using the Nottingham power rig, and muscle quality (W/kg; the ratio of leg extension power [W] to lower-body mineral-free lean mass [kg]). A composite measure of physical function was obtained by summing Z scores from the 6-minute walk, 8-ft up-and-go test, and 30-second chair-stand test. RESULTS: As expected, men had significantly greater levels of physical activity, lower adiposity, greater lean mass, higher leg extension power, and greater muscle quality compared with women (all P < 0.05). In linear regression analyses, muscle quality and physical activity were the strongest predictors of lower-extremity physical function in men and independently explained 42% and 29% of the variance, respectively. In women, muscle quality (16%) and percent body fat (12%) were independent predictors after adjustment for covariates. CONCLUSIONS: Muscle quality is the strongest predictor of lower-extremity physical function in men and women, but sex impacts the importance of physical activity and adiposity. These findings suggest that older men and women may benefit from different intervention strategies for preventing physical disability and also highlight the importance of weight management for older women to preserve physical function. PMID- 25137243 TI - Low-dose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause. AB - OBJECTIVE: Sleep disturbances are common among women in midlife; prevalence increases among perimenopausal/postmenopausal women with vasomotor symptoms. Paroxetine 7.5 mg is the only nonhormonal treatment that has been approved in the United States for moderate to severe vasomotor symptoms associated with menopause. In two pivotal phase 3 studies evaluating its efficacy and safety, improvements in sleep disturbances were also prospectively evaluated. METHODS: Postmenopausal women with moderate to severe vasomotor symptoms were randomly assigned to paroxetine 7.5 mg (n = 591) or placebo (n = 593) once daily for 12 weeks (both studies) or 24 weeks (24-wk study). Predefined assessments on weeks 4, 12, and 24 included number of nighttime awakenings attributed to vasomotor symptoms, sleep-onset latency, sleep duration, and sleep-related adverse events. The two studies' data for weeks 1 to 12 were pooled. RESULTS: At baseline, participants reported a mean of 3.6 awakenings/night attributed to vasomotor symptoms. Nighttime awakenings attributed to vasomotor symptoms were significantly reduced within 4 weeks of initiating paroxetine 7.5 mg treatment (39% reduction vs 28% for placebo; P = 0.0049), and reductions were sustained through 12 or 24 weeks of treatment. Paroxetine 7.5 mg treatment also significantly increased nighttime sleep duration (week 4, +31 vs +16 min for placebo; P = 0.0075), but no significant between-group differences in sleep-onset latency or sleep-related adverse events such as sedation were observed. CONCLUSIONS: In postmenopausal women treated for menopausal vasomotor symptoms, paroxetine 7.5 mg significantly reduces the number of nighttime awakenings attributed to vasomotor symptoms and increases sleep duration without differentially affecting sleep-onset latency or sedation. PMID- 25137245 TI - Feelings of energy are associated with physical activity and sleep quality, but not adiposity, in middle-aged postmenopausal women. AB - OBJECTIVE: Feelings of fatigue and low energy are widespread among middle-aged women and have been shown to negatively affect quality of life. The aim of the present study was to examine the associations among adiposity, physical activity, and feelings of fatigue and energy in postmenopausal women. METHODS: Postmenopausal women (N = 74; mean [SD] age, 58.9 [3.8] y) were assessed for adiposity (via dual-energy x-ray absorptiometry), steps per day, minutes of moderate to vigorous physical activity per day (via an accelerometer), prior week intensity of psychological vigor (via the Profile of Mood States-Short Form), and prior month frequency of energy feelings (via the vitality scale of the 36-item Medical Outcomes Survey--Short Form). Sleep quality was measured using the Pittsburgh Sleep Quality Index, depression was measured using the Beck Depression Inventory-II, and perceived stress was measured using the Perceived Stress Scale. RESULTS: Adiposity was negatively related to steps per day (r = -0.55, P < 0.05) and minutes of moderate to vigorous physical activity per day (r = -0.48, P < 0.05). Adiposity was not significantly related to vigor, vitality, or any other psychological measures. Greater vitality was associated with lower total number of medications (r = -0.31, P < 0.01), more steps per day (r = 0.28, P < 0.05), and higher minutes of moderate to vigorous physical activity per day (r = 0.37, P < 0.01). Prior week feelings of vigor were unrelated to any variable of interest. Regression analyses revealed that minutes of moderate to vigorous physical activity per day independently explained 8% of the variance in vitality, whereas sleep quality was also a significant predictor of vitality (both P < 0.05). CONCLUSIONS: Engaging in recommended amounts of moderate to vigorous physical activity per day is associated with higher monthly frequency of energy feelings, regardless of adiposity status, in middle-aged postmenopausal women. PMID- 25137248 TI - Theoretical study for OH radical-initiated atmospheric oxidation of ethyl acrylate. AB - OH radical-initiated atmospheric oxidation of ethyl acrylate (ethyl 2-propenoate, EA) has been investigated by performing density functional theory (DFT) calculations. Optimizations of the reactants, intermediates, transition states and products were carried out at the MPWB1K/6-31+G(d,p) level. Single-point energy calculations were performed at the MPWB1K/6-311+G(3df,2p) level of theory. The detailed oxidation mechanism was presented and discussed. The results show that the OH addition is more energetically favorable than the H abstraction. Rice Ramsperger-Kassel-Marcus (RRKM) theory was used to predict the rate constants over the possible atmospheric temperature range of 180-370 K. The Arrhenius expression adequately describes the total rate constant: k(EA+OH)=(1.71*10( 12))exp(805.42/T)cm(3) molecule(-1) s(-1). At 298 K, the atmospheric lifetime of ethyl acrylate determined by OH radicals is about 16.2h. In order to find out the effect of alkyl substitution on the reaction activity, rate constants for the reactions of methyl acrylate, methyl methacrylate and butyl acrylate with OH radicals were also discussed. Calculation results show that the reaction activity may increase with the increased electron-donating substitution for electrophilic addition reaction. PMID- 25137246 TI - Ethics, economics, and the use of primaquine to reduce falciparum malaria transmission in asymptomatic populations. AB - Yoel Lubell and colleagues consider ethical and economic perspectives on mass drug administration of primaquine to limit transmission of P. falciparum malaria. Please see later in the article for the Editors' Summary. PMID- 25137249 TI - Preparation, anti-trypanosomal activity and localisation of a series of dipeptide based vinyl sulfones. AB - An improved, Weinreb amide-based, synthesis of anti-trypanosomal lysine containing vinyl sulfones is described incorporating, as a feature, diversity at the epsilon-lysine amino group. Members of this family demonstrated moderate to good efficacy as anti-trypanosomal agents and a fluorescent dansyl (19) derivative was used to investigate subcellular localisation of the compound class. PMID- 25137250 TI - Twisted intramolecular charge transfer and its contribution to the NLO activity of Diglycine Picrate: a vibrational spectroscopic study. AB - Single crystals of Diglycine Picrate (DGLP) were grown by slow evaporation technique and the vibrational spectral analysis is carried out using FT Raman and FT-IR spectroscopy, supported by Density Functional Theoretical (DFT) computations to derive equilibrium geometry, vibrational wavenumbers and first hyperpolarizability. The vibrational spectra confirm the existence of NH3(+) in DGLP. The influence of Twisted Intramolecular Charge Transfer (TICT) caused by the strong ionic ground state hydrogen bonding between charged species making DGLP crystal to have the non-centrosymmetric structure has been discussed. The Natural Bond Orbital (NBO) analysis confirms the occurrence of strong intermolecular N-H?O hydrogen bond. The HOMO-LUMO energy gap and the first order hyperpolarizability were calculated and it supports the nonlinear optical activity of the Diglycine Picrate crystal. PMID- 25137251 TI - Recombination blurs phylogenetic groups routine assignment in Escherichia coli: setting the record straight. AB - The characterization of population structures plays a main role for understanding outbreaks and the dynamics of bacterial spreading. In Escherichia coli, the widely used combination of multiplex-PCR scheme together with goeBURST has some limitations. The purpose of this study is to show that the combination of different phylogenetic approaches based on concatenated sequences of MLST genes results in a more precise assignment of E. coli phylogenetic groups, complete understanding of population structure and reconstruction of ancestral clones. A collection of 80 Escherichia coli strains of different origins was analyzed following the Clermont and Doumith's multiplex-PCR schemes. Doumith's multiplex PCR showed only 1.7% of misassignment, whereas Clermont's-2000 protocol reached 14.0%, although the discrepancies reached 30% and 38.7% respectively when recombinant C, F and E phylogroups were considered. Therefore, correct phylogroup attribution is highly variable and depends on the clonal composition of the sample. As far as population structure of these E. coli strains, including 48 E. coli genomes from GenBank, goeBURST provides a quite dispersed population structure; whereas NeighborNet approach reveals a complex population structure. MLST-based eBURST can infer different founder genotypes, for instance ST23/ST88 could be detected as the founder genotypes for STC23; however, phylogenetic reconstructions might suggest ST410 as the ancestor clone and several evolutionary trajectories with different founders. To improve our routine understanding of E. coli molecular epidemiology, we propose a strategy based on three successive steps; first, to discriminate three main groups A/B1/C, D/F/E and B2 following Doumith's protocol; second, visualization of population structure based on MLST genes according to goeBURST, using NeighborNet to establish more complex relationships among STs; and third, to perform, a cost free characterization of evolutionary trajectories in variants emerging along the clonal expansion using parsimony methods of phylogenetic analysis. PMID- 25137252 TI - Thrombopoietin treatment of one graft in a double cord blood transplant provides early platelet recovery while contributing to long-term engraftment in NSG mice. AB - Human cord blood (CB) hematopoietic stem cell (HSC) transplants demonstrate delayed early neutrophil and platelet recovery and delayed longer term immune reconstitution compared to bone marrow and mobilized peripheral blood transplants. Despite advances in enhancing early neutrophil engraftment, platelet recovery after CB transplantation is not significantly altered when compared to contemporaneous controls. Recent studies have identified a platelet-biased murine HSC subset, maintained by thrombopoietin (TPO), which has enhanced capacity for short- and long-term platelet reconstitution, can self-renew, and can give rise to myeloid- and lymphoid-biased HSCs. In previous studies, we have shown that transplantation of human CB CD34(+) cells precultured in TPO as a single graft accelerates early platelet recovery as well as yielding long-term repopulation in immune-deficient mice. In this study, using a double CB murine transplant model, we investigated whether TPO cultured human CB CD34(+) cells have a competitive advantage or disadvantage over untreated human CB CD34(+) cells in terms of (1) short-term and longer term platelet recovery and (2) longer term hematological recovery. Our studies demonstrate that the TPO treated graft shows accelerated early platelet recovery without impairing the platelet engraftment of untreated CD34(+) cells. Notably, this was followed by a dominant contribution to platelet production through the untreated CD34(+) cell graft over the intermediate to longer term. Furthermore, although the contribution of the TPO treated graft to long-term hematological engraftment was reduced, the TPO treated and untreated grafts both contributed significantly to long-term chimerism in vivo. PMID- 25137253 TI - Does a no-take marine protected area benefit seahorses? AB - Seahorses are iconic charismatic species that are often used to 'champion' marine conservation causes around the world. As they are threatened in many countries by over-exploitation and habitat loss, marine protected areas (MPAs) could help with their protection and recovery. MPAs may conserve seahorses through protecting essential habitats and removing fishing pressures. Populations of White's seahorse, Hippocampus whitei, a species endemic to New South Wales, Australia, were monitored monthly from 2006 to 2009 using diver surveys at two sites within a no-take marine protected areas established in 1983, and at two control sites outside the no-take MPA sites. Predators of H. whitei were also identified and monitored. Hippocampus whitei were more abundant at the control sites. Seahorse predators (3 species of fish and 2 species of octopus) were more abundant within the no-take MPA sites. Seahorse and predator abundances were negatively correlated. Substantial variability in the seahorse population at one of the control sites reinforced the importance of long-term monitoring and use of multiple control sites to assess the outcomes of MPAs for seahorses. MPAs should be used cautiously to conserve seahorse populations as there is the risk of a negative impact through increased predator abundance. PMID- 25137254 TI - Chemical modulation of mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenics. AB - Schizophrenia is a complex and highly heterogeneous psychiatric disorder whose precise etiology remains elusive. While genome-wide association studies (GWAS) have identified risk genes, they have failed to determine if rare coding single nucleotide polymorphisms (nsSNPs) contribute in schizophrenia. Recently, two independent studies identified 12 rare, deleterious nsSNPS in the GRM1 gene, which encodes the metabotropic glutamate receptor subtype 1 (mGlu1), in schizophrenic patients. Here, we generated stable cell lines expressing the mGlu1 mutant receptors and assessed their pharmacology. Using both the endogenous agonist glutamate and the synthetic agonist DHPG, we found that several of the mutant mGlu1 receptors displayed a loss of function that was not due to a loss in plasma membrane expression. Due to a lack of mGlu1 positive allosteric modulators (PAM) tool compounds active at human mGlu1, we optimized a known mGlu4 PAM/mGlu1 NAM chemotype into a series of potent and selective mGlu1 PAMs by virtue of a double "molecular switch". Employing mGlu1 PAMs from multiple chemotypes, we demonstrate that the mutant receptors can be potentiated by small molecules and in some cases efficacy restored to that comparable to wild type mGlu1 receptors, suggesting deficits in patients with schizophrenia due to these mutations may be amenable to intervention with an mGlu1 PAM. However, in wild type animals, mGlu1 negative allosteric modulators (NAMs) are efficacious in classic models predictive of antipsychotic activity, whereas we show that mGlu1 PAMs have no effect to slight potentiation in these models. These data further highlight the heterogeneity of schizophrenia and the critical role of patient selection strategies in psychiatric clinical trials to match genotype with therapeutic mechanism. PMID- 25137255 TI - Comparison of mercury contamination in live and dead dolphins from a newly described species, Tursiops australis. AB - Globally it is estimated that up to 37% of all marine mammals are at a risk of extinction, due in particular to human impacts, including coastal pollution. Dolphins are known to be at risk from anthropogenic contaminants due to their longevity and high trophic position. While it is known that beach-cast animals are often high in contaminants, it has not been possible to determine whether levels may also be high in live animals from the same populations. In this paper we quantitatively assess mercury contamination in the two main populations of a newly described dolphin species from south eastern Australia, Tursiops australis. This species appear to be limited to coastal waters in close proximity to a major urban centre, and as such is likely to be vulnerable to anthropogenic pollution. For the first time, we were able to compare blubber mercury concentrations from biopsy samples of live individuals and necropsies of beach-cast animals and show that beach-cast animals were highly contaminated with mercury, at almost three times the levels found in live animals. Levels in live animals were also high, and are attributable to chronic low dose exposure to mercury from the dolphin's diet. Measurable levels of mercury were found in a number of important prey fish species. This illustrates the potential for low dose toxins in the environment to pass through marine food webs and potentially contribute to marine mammal deaths. This study demonstrates the potential use of blubber from biopsy samples to make inferences about the health of dolphins exposed to mercury. PMID- 25137256 TI - Document of standardization of enteral nutrition access in adults. AB - The group of standardization and protocols of the Spanish Society of Parenteral and Enteral Nutrition (SENPE) published in 2011 a consensus document SENPE/SEGHNP/ANECIPN/SECP on enteral access for paediatric nutritional support. Along the lines of this document, we have developed another document on adult patients to homogenize the clinical practice and improve the quality of care in enteral access in this age group. The working group included health professionals (nurses, dietitians and doctor) with extensive experience in enteral nutrition and access. We tried to find scientific evidence through a literature review and we used the criteria of the Agency for Health-care Research and Quality (AHRQ) to classify the evidence (Grade of Recommendation A, B or C). Later the document was reviewed by external experts to the group and requested the endorsement of the Scientific and Educational Committee (CCE) and the group of home artificial nutrition (NADYA) of the SENPE. The full text will be published as a monograph number in this journal. PMID- 25137257 TI - [Mobile applications for nutrition, dietetics and healthy habits; analysis and consequences of an increasing trend]. AB - A mobile application or app, is a software designed for smartphones and other mobile devices. Nowadays these have undergone a boom in its users offer and diversity, entering the field of medicine, for both professionals and patients. In "health apps" category, there is a part for the field of nutrition. It is estimated that in the category of "diet and fitness" more than 5,400 apps. AIM: Reviewing apps, to make a diagnosis of the quality and validity, and review studies witch incorporating apps as part of the project s methodology. METHODS: Literature search in major scientific databases, PubMed , SciELO , EMBASE (last 5 years) . In the other hand, a search was conducted in the Android APPs Store, 7 Key words were introduced in the form of APPs Sotre to analyze the top 5 of each search. RESULTS: 95 Apps were analyzed, and others used from research studies. The apps found to be an option as strategies for improvement and prevention of certain diseases related to nutrition, exercise and daily habits, both from the individual used or as professionals, but include the unreliability of the majority. From the 95 apps analyzed, 51.57% were classified as "low quality". CONCLUSION: Although most applications are not useful or safe, if in the future are normalized and improved, they could provide a useful tool for the healthcare system and society. PMID- 25137258 TI - Hypertriglyceridemic waist phenotype: association with metabolic disorders and visceral fat in adults. AB - OBJECTIVE: To evaluate the association of Hypertriglyceridemic waist with metabolic disorders and visceral fat in adults. METHODS: Cross-sectional study with 191 individuals of both sexes. Subjects were grouped according to Waist Circumference (WC) ratings (Men: > 90 cm; Women: > 80 cm) and triglycerides (TG) (> 150 mg/dl) in Group 1 (HTW Phenotype): elevated WC and TG; Group 2 (absence of HTW Phenotype): elevated WC and normal TG or normal WC and elevated TG or normal WC and TG. Metabolic alternations, visceral adipose tissue (VAT) and visceral/subcutaneous fat index (VF/SF) measured by computed tomography were evaluated as cardiovascu - lar risk factors between the groups. RESULTS: Individuals with HTW phenotype, 82% had three or more cardiovascular risk factors. The association between cardiovascular risk factors with HTW phenotype revealed that among men 73.7% had hypercholesterolemia, 94.9% elevated non-HDLc and 78.9% excess of VAT area (p = 0.001). Among women, 65% had elevated Sistolic Blood Plessure, 80% hypercholesterolemia and 90% elevated non-HDLc (p < 0.02). CONCLUSION: The HTW phenotype associated with the metabolic alternations and VAT excess. Individuals with HTW had higher number of cardiovascular risk factors. The Hypertriglyceridemic waist can be used in clinical practice for investigating cardiovascular risk and visceral adipose tissue in individuals. PMID- 25137259 TI - Psychological well-being in a sample of obese patients compared with a control group. AB - INTRODUCTION: The literature has found that obese patients usually report more depression and anxiety than normal weight individuals. However, not many investigations have studied the relationship between obesity and quality of life from a Positive Psychology approach. OBJECTIVE: In this study it is analyzed if obese patients have less psychological well-being than a control group (normal weight participants). METHOD: A total of 221 participants (111 obese individuals and 110 controls) were selected to conduct the study. To measure psychological well-being, the Spanish version of the Ryff's Scales was used. To measure mental health, the Spanish version of the mental health component of the Short Form 36 Health Survey (SF-36) was used. RESULTS: It was found that obese participants reported less psychological well-being than normal weight individuals, but that there were not statistically significant differences in the case of mental health measured with the SF-36. DISCUSSION: According to the results, it can be concluded that reports of psychological well-being problems were much more common in participants with weight problems than in the control group. PMID- 25137260 TI - Beliefs, attitudes and phobias among Mexican medical and psychology students towards people with obesity. AB - BACKGROUND: A high prevalence of stigmatizing attitude among healthcare personnel towards obese people has been reported. OBJECTIVE: To evaluate the beliefs, attitudes and phobias that Mexican medical and psychology students have towards obese people. METHODS: A cross-sectional study was conducted with 528 students enrolled at the Autonomous University of Baja California in psychology and medical schools. Weight, height and waist circumference were evaluated. Beliefs about obesity were assessed with the BAOP scale, attitudes towards obese people by the ATOP scale and obesity phobias by the F-scale. RESULTS: Participants achieved a mean F-scale score of 3.4. Only seven per cent showed neutral or positive attitudes towards obesity (<=?2.5). Less fat phobia was associated with beliefs that obesity was not a result of the person's self-control (p = 0.0001) and had better attitudes towards obese people (p = 0.0001). Men had higher risk of fat phobia (OR = 1.5). CONCLUSIONS: High prevalence of phobias and negative attitudes towards obesity was observed. Men had higher stigma. PMID- 25137261 TI - Genome-wide screen of promoter methylation identifies novel markers in diet induced obese mice. AB - OBJECTIVE: To investigate the genome-wide promoter methylation and gene expression for the identification of methylation markers in obesity. METHODS: Using a high-fat, diet-induced obese mouse model, we performed comprehensive DNA methylation profiling of gene promoters to determine the differentially methylated genes using methylated DNA immunoprecipitation followed by hybridization to the NimbleGen MM8 CpG plus Promoter Microarray. We further integrated epigenomics data with gene expression profiling to identify promoters exhibiting an association between methylation status and the expression of downstream genes. RESULTS: A total of 24 hypermethylated promoters and 42 hypomethylated promoters in epididymal fat were selected as methylation markers, which were associated with downregulated and upregulated gene expression, respectively. The promoter methylation and differential gene expression of three markers (Mmp2, Foxj3 and Ube2q2) in the fat were validated by sequencing bisulfitemodified DNA and real-time reverse transcriptase PCR. The genes with these differentially methylated promoters and the associated transcriptional expression in the fat were primarily involved in biological activities in lipid metabolism and storage, cellular differentiation, immunity and the pathogenesis of obesity-related complications. CONCLUSIONS: This study represents the first effort to determine methylation markers in obese mice that may regulate gene transcription in obesity. Our approach has potential relevance for clinical applications by identifying markers useful in elucidating the mechanisms of obesity pathogenesis and its complications. PMID- 25137262 TI - Short term low-calorie diet improves insulin sensitivity and metabolic parameters in obese women. AB - Obesity and insulin resistance are associated with an increase of cardiovascular risk factors, including adipocytokines. The aim of this study was to investigate the effect of low-calorie diet on serum lipids, adipokines, insulin resistance and body composition in obese women. It was a clinical trial with class I obese women aged 30-45 years submitted to hypocaloric diet for 90 days. Dietary intake, anthropometric parameters, body composition, serum lipids, glucose, insulin, leptin, adiponectin, HOMA-IR and QUICKI indexes were evaluated at the baseline, 30, 60 and 90 days. There was 30% significant decrease in energy intake, and also decrease in body weight, body mass index and waist circumference (p < 0.01) throughout the treatment period. Despite the amount of lean body mass (kg) reduced in average, it was observed that lean body mass (%) had increased (p < 0.01) and that the amount of fat body mass (kg) had decreased significantly in the third month (p < 0.05). Systolic blood pressure reduced up to -5mmHg (p < 0.05) after 90 days. Was observed a decrease (p < 0.05) on serum insulin and HOMA IR until the 60th day, while the serum adiponectin increased (p < 0.01) during treatment. Corroborating with the reduction of fat body mass and weight, serum leptin also reduced (p < 0.01). These results suggest that the short-term low calorie diet reduces total body fat, mainly found in the abdominal region, and efficiently improve insulin sensitivity decreasing cardiovascular risk in obese women. PMID- 25137263 TI - The relationship between dental caries and obesity among primary school children aged 5 to 14 years. AB - BACKGROUND: Previous study revealed that the link between dental caries and obesity has been controversial. The purpose of this research is to investigate the association between dental caries and obesity among primary school children in Wannan area, China. METHODS: A cross-sectional study was designed to collect the routine health screening data for primary school children aged 5-14 years in Wannan area,China, Overweight and obesity status were determined using the International Obesity Task Force standard (IOTF) BMI cut-off points. Caries status was recorded based on WHO recommendations. RESULTS: Our results revealed that the overall caries prevalence of the subjects was 44.9%, Maximum number of caries affected children belonged to underweight and normal group, followed by overweight, and the least number was obesity. These differences were statistically significant (chi-square test, P < 0.001). Children with obesity were 1.908 times (OR =1.908; CI95%=1.750, 2.079) more likely have caries than children with underweight or health weight. Overweight children were 1.547 times (OR = 1.547; CI95% = 1.479, 1.618) more likely to have caries than children with underweight or health weight. After adjusted the gender and age, a statistically significant association was also observed between body mass index categories and caries. CONCLUSIONS: Obesity may have a significant effect on caries prevalence of primary school children in Wannan area, China. The importance of obesity should not only be emphasized with respect to general diseases but also with regard to carious lesions. PMID- 25137264 TI - Association between nutritional status, C-reactive protein, adiponectin and HOMA AD in Brazilian children. AB - INTRODUCTION: In children, the presence of obesity is a major risk factor for the occurrence of cardiovascular diseases on the adulthood. OBJECTIVE: To evaluate the association of anthropometry, body composition, clinical variables and biochemical profile with C-reactive protein and adiponectin levels, and insulin resistance in children in the municipality of Nova Era, Brazil. METHODS: Nested case-control study following a crosssectional study. We evaluated 178 children, 57 of them classified as obese and 121 as normal-weight from a population of 1024 schoolchildren 6 to 10 years old: Blood samples were collected after 12-hour fast to obtain serum and plasma. We collected anthropometric and body composition measures, systolic and diastolic blood pressure data. Sexual maturation was assessed according to the stage of sexual development. We performed Student's t test, Mann-Whitney U test, Pearson's correlation, Spearman's test and multiple linear regression analysis. Independent variables with p < 0.05 were included in the multiple regression model. Residual analysis was performed to assess model validity. RESULTS: Among obese children, C-reactive protein levels were associated with triacylglycerol levels and body fat percentage estimated by skinfold thickness (R2 adjusted = 27.6%, p < 0.001). Adiponectin was associated with HOMA-IR, HOMAAD and body fat percentage estimated by skinfold thickness (R2 adjusted = 75.5%, p < 0.001). HOMA-AD index was associated with HOMA-IR, adiponectin, systolic blood pressure and weight (R2 adjusted = 90.7%, p < 0.001). CONCLUSION: Significant associations were found between body composition, anthropometry, clinical variables, biochemical profile and adiponectin and C reactive protein levels and insulin resistance in obese and normal-weight children. PMID- 25137265 TI - Common variants in genes related to lipid and energy metabolism are associated with weight loss after an intervention in overweight/obese adolescents. AB - BACKGROUND: Some SNPs related to lipid and energy metabolism may be implicated not only in the development of obesity and associated comorbidities, but also in the weight loss response after a nutritional intervention. OBJECTIVE: In this context, the present study analyzed four SNPs located within four genes known to be associated with obesity and other obesity-related complications, and their putative role in a weight-loss intervention in overweight/obese adolescents. METHODS: The study population consisted of 199 overweight/obese adolescents (13 16 yr old) undergoing 10 weeks of a weight loss multidisciplinary intervention: the EVASYON programme (www.estudioevasyon.org). Adolescents were genotyped for 4 SNPs, and anthropometric measurements and biochemical markers were analyzed at the beginning and after the intervention. RESULTS: Interestingly, APOA5(rs662799) was associated with the baseline anthropometric and biochemical outcomes, whereas FTO (rs9939609) seemed to be related with the change of these values after the 10 week intervention. The other two SNPs, located in the CETP (rs1800777) and the APOA1 (rs670) genes, showed important relationships with adiposity markers. Specifically, a combined model including both SNPs turned up to explain up to 24% of BMI-SDS change after 10 weeks of the multidisciplinary intervention, which may contribute to under - stand the weight loss response. CONCLUSION: Common variants in genes related to lipid and energy metabolism may influence not only biochemical outcomes but also weight loss response after a multidisciplinary intervention carried out in obese/overweight adolescents.. PMID- 25137266 TI - Finding new solutions in pediatric parenteral admixtures: how to improve quality and to deal with shortages. AB - INTRODUCTION: Pediatric parenteral nutrition enables normal growth even of preterm infants. Those children require, however, tailored parenteral nutrition and the creation of such can be challenging due to the risk of instability and shortages. OBJECTIVE: Prototypical parenteral admixtures were created using different calcium salts (organic and inorganic) and different lipid emulsions and tested for stability. 36 of parenteral admixtures containing two types of calcium salts: chloride or gluconolactobionate and different lipid emulsions (SMOFlipid(r) or Lipofundin MCT/LCT(r)) were under investigation. METHODS: Preliminary admixtures were prepared in two-chamber bags whereas lipid emulsions were placed separately in the second chamber. Pre-admixtures were stored for up to 21 days at +4oC. Contents of the two chambers were combined at t = 0 or after 21 days of storage. Physical analysis of completed admixtures (visual inspection, microscopic observation, pH measurement and determination of the size distribution of oily droplets) was carried out after 21 days of the storage. Stability of lipid, commercial emulsions stored in ethylene vinyl acetate (EVA) bags for 42 days was also studied. RESULTS: Irrespectively of the time of storage of preadmixtures and type of calcium salt and different lipid emulsions among 36 total parenteral admixtures only one showed signs of destabilization after preparation and one was unstable when stored for longer than 14 days. All other formulations were qualified to be stable during the study. All investigated commercial lipid emulsions were physically stable in EVA bags even when stored at room temperature. CONCLUSION: The study proved that it was possible to store pre admixture in EVA bags for 21 days at 4 degrees C as well as that CAN (critical aggregation number) and CaxP (the products of multiplication of calcium and phosphate ions concentration) should not be used as reliable indicators of admixture physical stability. No influence of the type of calcium salts on stability of admixtures was observed. PMID- 25137267 TI - Effect of long-term physical exercise program and/or diet on metabolic syndrome in obese boys. AB - INTRODUCTION: There have been just a few studies examining the influence of detraining on obese boys. They conclude that any gains regress to the untrained control values during the detraining period. OBJECTIVE: The objective of the present study was thus to evaluate the effects of detraining (6 months) on metabolic syndrome after two types of intervention (both 31 months), one of an exercise program alone and the other of a diet-plus-exercise program, in obese boys. METHODS: The participants were 18 sedentary boys (8- 11 years old) with a body mass index equal or greater than the 97th percentile for the age and sex (male) of the subject, without any dysfunction or metabolic problem. The participants were divided into two groups - the E group (physical exercise program) and the E+D group (physical exercise program plus a low calorie diet). Metabolic parameters were evaluated (TC, HDL, LDL, TG, glucose, insulin, Systolic Blood Pressure, and Diastolic Blood Pressure), allowing the metabolic syndrome index to be calculated. RESULTS: Changes were observed in LDL-C (effect sizes = 3.19 and -2.28) and in the LDL-C/HDL-C ratio (effect sizes = -3.02 and -1.16) in the E and E+D groups, respectively. The prevalence of metabolic syndrome and obesity was completely removed only in the E group (100% norisk and non-obese subjects - < 90th percentile). CONCLUSIONS: Detraining from a long-term exercise program (with or without diet) seems not to negatively affect the cardiovascular profile, suggesting that the program provides benefits and fosters healthy habits that can be maintained over time, preventing the development of metabolic syndrome. PMID- 25137268 TI - [Sensory evaluation of enteral nutritional supplements]. AB - INTRODUCTION AND OBJECTIVES: Enteral nutrition (EN) is indicated in patients who, although they may not eat enough food, maintain a sufficient function to receive, digest and absorb nutrients digestive system. Oral Nutritional Supplements (SON) are nutritionally complete or incomplete formulas (depending on whether or not provide all the nutrients needed to serve as the sole source of nutrients), which supplement inadequate oral diet. This study aims to evaluate the organoleptic characteristics of hyperproteic, normoproteic and fiber-enriched oral SON. MATERIAL AND METHODS: SON test, carried out at the Department of Endocrinology and Nutrition Consortium Hospital General Universitario de Valencia from October 2012 to February 2013. 137 SON were evaluated in total, of which 47 were hyperproteic, 46 normoproteic and 44 enriched in fiber. RESULTS: Of the SON evaluated in the group of hyperproteic the following 3 SON obtained the best scores: Fresenius Prot Energy Drink(r) (21,27, vanilla flavor), Avant Standard Nut(r) (20.3 , strawberry flavor) and Resource(r) Protein (20.01, chocolate flavor) In the group of normoproteic SON the 3 best rated were: Ensure Plus(r) (22.3, banana flavor), Ensure Plus(r) (21.9, peach flavor) and Fresubin Energy Drink(r) (21, strawberry flavor) In the group of fiber-enriched the 3 SON most appreciated were: 2 Kcal Fresubin Fibre Drink(r) (23.78, vanilla flavor), Ensure Plus(r) TwoCal (22.9, banana flavor) and Fortimel Compact(r) (21.5, strawberry flavor) CONCLUSIONS: The study aims to guide clinicians on what SON may be more acceptable to the patient, so that the SON serve their purpose and restore or improve nutritional status, as the SON intervention is safe and cost - effective, since they improve both the functionality and quality of life. PMID- 25137269 TI - [Anti-inflammatory activity of olive seed polyphenolic extract in the THP1-XBLUE CD14 human monocytes cell line]. AB - The aim of this study was to assess the anti-inflammatory activity of a polyphenolic extract from olive pits. MATERIAL AND METHODS: The THP1-XBlue-CD14 (invivogen) cellular line, 80,000 cells/well, was incubated and inflammation (activation of NF-kb) was produced with 0.1 mg/mL of LPS (lipopolysaccharide from E. coli) for 24 hours. We assessed the presence of the extract (10 and 50 mg/L, biologically safe concentrations) for 2 hours at 37o C, before (preventive effect) and after (therapeutic effect) the proinflammatory activation, and the activity of alkaline phosphatase, which is expressed under the control of the NF kb transcriptional factor, was quantified by colorimetry. The percentage of activity of NF-kb as preventive effect and therapeutic effect was assessed by comparing it to control cultures of cells with LPS and without extract, which are considered 100% of NF-kb. RESULTS: The preventive anti-inflammatory capacity of the extract at 50 mg/L was 25.5% (95% CI: 16.8-34.2) and the therapeutic effect 34.9% (95% CI: 25.3-44.4) for the same concentration, without any significant activity at 10 mg/L. CONCLUSION: An activity of polyphenols extracted from olive pits is shown, both in preventing inflammation and therapeutically eliminating inflammation through inhibition of NF-kB factor previously activated by LPS at concentrations of 50 mg/L of polyphenols, which previously haven been shown to be safe. PMID- 25137270 TI - Fat-soluble vitamin deficiencies after bariatric surgery could be misleading if they are not appropriately adjusted. AB - OBJECTIVE: To evaluate the differences in frequency of fat-soluble vitamin deficiencies if we adjust their levels by its main carriers in plasma in patients undergoing Biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGB). RESEARCH METHODS & PROCEDURES: We recruited 178 patients who underwent RYGB (n = 116 patients) and BPD (n = 62 patients) in a single centre. Basal data information and one-year after surgery included: anthropometric measurements, fat soluble vitamins A, E and D, retinol binding protein (RBP) and total cholesterol as carriers of vitamin A and E respectively. Continuous data were compared using T-Student and proportions using chisquare test. RESULTS: There was a vitamin D deficiency of 96% of all patients, 10% vitamin A deficiency and 1.2% vitamin E deficiency prior to surgery. One year after surgery, 33% of patients were vitamin A deficient but the frequency reduced to 19% when we adjusted by RBP. We found a vitamin E deficiency frequency of 0% in RYGB and 4.8% in DBP one year after surgery. However, when we adjusted the serum levels to total cholesterol, we found an increased frequency of 8.7% in RYGB group for vitamin E deficiency and 21.4% in DBP (p = 0.04). CONCLUSION: We have found a different frequency of deficit for fat-soluble vitamin both in BPD and RYGB once we have adjusted for its main carriers. This is clinically relevant to prevent from overexposure and toxicity. We suggest that carrier molecules should be routinely requested when we assess fat-soluble vitamin status in patients who undergo malabsorptive procedures. PMID- 25137271 TI - High prevalence of vitamin D insufficiency among elite Spanish athletes the importance of outdoor training adaptation. AB - INTRODUCTION: The discovery of vitamin D muscle receptors in the last few years suggested a significant role in muscle tissue, pointing out athletes as a special group. Specific data are scarce. AIM: The main aim of the current paper was to provide, for the first time, comparable data about vitamin D status in elite Spanish athletes by sport, age, season and training environment. METHODS: Four hundred and eight elite athletes with a mean age of 22.8 +/- 8.4 years were recruited from the High-performance sport centre in Barcelona for this cross sectional study. Athletes from 34 different sports modalities were analysed. Data were available for vitamin D status, training environment, seasonality and number of medical visits. All data were analysed using SPSS version 18.0. RESULTS: Mean 25(OH)D of all athletes was 56.7 +/- 23.4 nmol/L. Approximately 82% of the athletes were below the optimal levels, (< 75nmol/l), 45% had moderate deficient levels (< 50 nmol/L) and 6% had severe deficiency (< 27.5 nmol/L). We have observed a steady increase in 25(OH)D concentrations with increasing age (p < 0.01) Highest levels were observed in those subjects training outdoors compared with those training indoor (p. PMID- 25137272 TI - [Evaluation of a nutritional intervention among elderly people: the Edumay project]. AB - BACKGROUND: The adherence to a Mediterranean Dietary Pattern is associated with a morbi-mortality reduction, and with a better quality of life. OBJECTIVES: To evaluate a nutritional intervention among independent elderly people enrolled in an educational program to increase the knowledge of the food and daily diets, promoting a healthy dietary pattern. METHODS: Quasi-experimental design conducted in elderly participants who lived in foster home apartments owned by the City Council of Pamplona (n = 41). The intervention was based on six group sessions and an individual motivational session in a period of three months. Adherence to Mediterranean diet was evaluated through a 14-point scale previously validated. RESULTS: Eighty point five per cent of participants were women, with a median age of 79 years, the majority of them widowed (48.8%) and with primary education (58.5%). After the nutritional intervention the percentage of participants who consumed two or more servings of vegetables increased significantly versus the control group (p = 0.042). Similarly, in comparison with the control group, there was an increase in the percentage of participants who consumed three servings per week of legumes (p = 0.042), three or more servings per week of nuts (p = 0.003), and those who consumed preferably meat from chicken, turkey, or rabbit instead of veal, pork, hamburgers, or sausages (p = 0.011). DISCUSSION: An intervention based on individual and group sessions improved significantly several parameters of a Mediterranean dietary pattern. PMID- 25137273 TI - The influence of nutritional status and disease on adiponectin and TNF-alpha; levels in colorectal cancer patients. AB - BACKGROUND: The aim of this study was to evaluate the association between adiponectin and tumor necrosis factor-alpha;?(TNF-alpha;) serum levels in colorectal cancer (CRC) patients and compare these levels to clinical stage and nutritional status. METHODS: A total of 79 patients were enrolled in the study (39 with CRC and 40 in the control). Nutritional status was assessed by Patient Generated Subjective Global Assessment (PG-SGA), body mass index (BMI), and phase angle (PhA). Adiponectin and TNF-alpha;?serum concentrations were determined using an enzyme-linked immunosorbent assay. RESULTS: Serum adiponectin levels were higher among CRC patients (p = 0.001). TNF-alpha;?serum levels were not significantly different between the groups, but patients with stage III or IV CRC had higher levels of TNF-alpha;?than those with lower stage disease (p = 0.037). The three tools used for the assessment of nutritional status (BMI, PhA, and PG SGA) demonstrated that patients with a more severe nutritional deficit had higher adipocytokine levels, although these differences were significant only to TNF- ?, when distributed PhA in tertiles. CONCLUSIONS: Adiponectin levels were higher among CRC patients. Although TNF-alpha;?serum levels from CRC patients did not differ significantly to the control group, CRC patients with stage III or IV had higher levels compared to those with stage I and II tumors. Nutritional status, as determined by BMI, PhA, and PG-SGA, demonstrated that patients with a greatest nutritional deficit, had higher levels of adipocytokines; however, these differences were significant only for TNF-?, when distributed PhA in tertiles. PMID- 25137274 TI - [Pilot study about the effectivity of an intervention based on games in nutritional status and muscle strength on children]. AB - INTRODUCTION: The overnutrition is a constant on developing countries; Chile is not an exception because it has a marked tendency to overweight and obesity in schoolchildren. The muscular strength has been associated with cardiovascular and metabolic health status in scholars. Effective interventions using games are needed to improve the nutritional status and physical fitness in school children. OBJECTIVE: To assess the intervention effectiveness based on games played at school time to improve the nutritional status and physical fitness in schoolchildren. METHOD: 156 students aged between 7 to 15 years, attending to two public schools with full school day, to which a pilot program was applied. This pilot program was based on dynamic recreational games during 45 minutes from monday to friday for 3 months in the largest playtime of the school day. RESULTS: At the end of the intervention, we observed a significant modification on children nutritional status, which highlights an increase in the number of children that reached the normal nutritional status (p < 0.001). We also observed a significant number of obese children who reached overweight nutritional status (p < 0.001). We also observed a decrease of leg muscular strength at the end of the study. CONCLUSIONS: We found a positive effect of a program based on dynamic recreational games in the largest school playtime, improving nutritional status. However, we didn't observed modifications in the muscular strength. PMID- 25137275 TI - [Design and validation of a questionnaire to assess dietary behavior in Mexican students in the area of health]. AB - INTRODUCTION: The dietary behavior (DB) establishes the relationship between the human being and foods and has an influence on nutrient intake and, therefore, it contributes to the health or disease status of a population, even among college students. There exit some validated instruments to assess food and nutrients intake, but there are very few assessing DB. OBJECTIVE: To design and validate a questionnaire to assess DB in Mexican college students. METHODS: According to the literature and Reasoned Theory, a questionnaire assessing DB was designed. Its logic and content validity was determined by expert assessment. It was applied on two occasions with a 4-week interval to 333 students from the University of Guadalajara coursing the sixth semester of Medicine or Nutrition. The reproducibility was assessed by means of the interclass correlation coefficient. The construct validity and the internal consistency were calculated by Rasch analysis, for both the difficulty of the items and the subjects' capability. RESULTS: The questionnaire finally included 31 questions with multiple choice answers. The interclass correlation coefficient of the instrument was 0.76. The Cronbach alpha was 0.50 for the subjects' capability and 0.98 for the internal consistency of the items. 87.1% of the subjects and 89.8% of the items had INFIT and OUTFIT values within acceptable limits. CONCLUSIONS: The present questionnaire has the potentiality of measuring at low cost and in a practical way aspects related with DB in college student with the aim of establishing or following-up corrective or preventive actions. PMID- 25137276 TI - Adherence to the Mediterranean diet by nursing students of Murcia (Spain). AB - INTRODUCTION: The Mediterranean diet is recognized as one with the healthiest dietary patterns; however, this diet is deteriorating and being abandoned even in the Mediterranean countries themselves. Generally speaking, dietary habits get fixed during adolescence although during the college phase, students may experience important changes in their lifestyles. The KIDMED index is recognized as a good tool to assess adherence to the Mediterranean diet (AMD). OBJECTIVE: The aim of this study was to assess AMD in college students and to evidence possible variations throughout the college period assessing differences between the college years. METHOD: A cross-sectional study with 213 alumni in first grade and 105 in fourth grade was carried out. The students were classified by gender, type of residence (parents' home or out of the parents' house) and body mass index (BMI) (< 25 or > 25). RESULTS: The BMI for the whole sample was 24.35 +/- 2.71 in men and 22.54 +/- 3.25 in women (p < 0.001). The mean score in AMD was 7.0 +/- 1.9, with 43% of the students showing good adherence. In general, a low intake of fruits, vegetables, rice or pasta was observed, foods that are included in the base of the dietary pyramid. Consumption of olive oil and legumes was very high and a direct relationship was observed between overweighed people (BMI > 25) and the habit of not having breakfast usually. No significant differences were observed between the student of first and fourth grades although those students in the fourth grade living away from the parental house had higher AMD level than the other students (p < 0.001). CONCLUSIONS: Educational programs promoting the intake of the different groups of food are recommended, was well as strategies promoting the consumption of fruits and vegetables within the university area and the healthy habit of having breakfast. PMID- 25137277 TI - [Prevalence of nutritional risk evaluated with NRS-2002 in Mexican oncology population]. AB - OBJECTIVE: Hospitalized patients have high risk of malnutrition, specially those with cancer. There are some screening tools that lead to the detection of malnutrition in hospitalized patients, as Nutritional Risk Screening 2002 (NRS 2002), which we used in Mexican population with cancer at the moment of hospital admission to determine the prevalence of malnutrition risk, and to determine as well as the best predictive item to measuring nutritional risk in our population. METHODOLOGY: Nutritional status in cancer patients with NRS 2002 during hospital admission was assessed. To the analysis of variable non statistical parametric tests, student-t test, Pearson and Spearman test, as well as ANOVA test were used. To determine the best item for predicting nutritional risk in Mexican population with cancer, a logistic regression test was applied. RESULTS: Of our population, 50.2% of were classified as patients in nutritional risk at hospital admission. Gender, age, normal levels of IMC lower than 20.5, food intake, weight loss and hematological cancer were associated with nutritional risk (p < 0.05). The best model of logistic regression for predicting nutritional risk were the same used by NRS-2002 questionnaire (p < 0.05). CONCLUSION: Malnutrition prevalence is high in cancer patients and NRS-2002 is a reliable tool for predicting nutritional risk in Mexican population with cancer. PMID- 25137278 TI - [Body composition and heart rate variability in patients with chronic obstructive pulmonary disease pulmonary rehabilitation candidates]. AB - Body composition is a non-invasive method, which gives us information about the distribution of tissues in the body structure, it is also an indicator of the risk of mortality in patients with chronic obstructive pulmonary disease. The heart rate variability is a technique that gives us information of autonomic physiological condition, being recognized as an indicator which is decreased in a number of diseases. The purpose of this study was to assess body composition and heart rate variability. The methodology used is that of Debora Kerr (1988) endorsed by the International Society for advances in Cineantropometria for body composition and heart rate variability of the guidelines described by the American Heart Association (1996). Roscraff equipment, caliper Slimguide and watch Polar RS 800CX was used. , BMI 26.7 +/- 3.9 kg / m2; Muscle Mass 26.1 +/- 6.3 kg ; Bone Mass 1.3 kg +/- 8.1 76 +/- 9.9 years Age : 14 candidates for pulmonary rehabilitation patients were evaluated , Adipose mass 16.4 +/- 3.6 kg ; FEV1 54 +/- 14%. Increased waist circumference and waist hip ratio was associated with a lower overall heart rate variability. The bone component was positively related to the variability of heart rate and patients with higher forced expiratory volume in one second had lower high frequency component in heart rate variability. In these patients, the heart rate variability is reduced globally and is associated with cardiovascular risk parameters. PMID- 25137279 TI - Hypomagnesaemia in critically ill patients with haematological malignancies. AB - INTRODUCTION: There is currently little information regarding the incidence of hypomagnesaemia and its impact on the prognosis of critically ill patients with haematological malignancies. OBJECTIVE: This study sought to describe the incidence of hypomagnesaemia in critically ill patients with haematological malignancies admitted to an oncological intensive care unit (ICU). METHODS: A total of 102 critically ill patients with haematological malignancies, who were 18 years of age and admitted to the ICU between January 2008 and April 2011, were included in this study. Hypomagnesaemia was defined as a serum magnesium concentration below 1.7 mg/dl. RESULTS: The incidence of hypomagnesaemia at admission or during the first 24 hours of stay in the ICU was 22.5% (23/102). The hospital mortality rates of patients with and without hypomagnesaemia were 47.8% and 60.7%, respectively. CONCLUSION: The incidence of hypomagnesaemia in critically ill patients with haematological malignancies was 22.5%. Mortality in the ICU and in the hospital was similar in patients with and without hypomagnesaemia. PMID- 25137280 TI - The calcium concentration of public drinking waters and bottled mineral waters in Spain and its contribution to satisfying nutritional needs. AB - INTRODUCTION: A sufficient intake of calcium enables correct bone mineralization. The bioavailability of calcium in water is similar to that in milk. OBJECTIVE: To determine the concentration of calcium in public drinking water and bottled mineral water. METHODS: We used ion chromatography to analyse the calcium concentrations of public drinking waters in a representative sample of 108 Spanish municipalities (21,290,707 people) and of 109 natural mineral waters sold in Spain, 97 of which were produced in Spain and 12 of which were imported. RESULTS: The average calcium concentration of public drinking waters was 38.96 +/ 32.44 mg/L (range: 0.40- 159.68 mg/L). In 27 municipalities, the water contained 50-100 mg/L of calcium and in six municipalities it contained over 100 mg/L. The average calcium concentration of the 97 Spanish natural mineral water brands was 39.6 mg/L (range: 0.6-610.1 mg/L). Of these, 34 contained 50-100 mg/L of calcium and six contained over 100 mg/L. Of the 12 imported brands, 10 contained over 50 mg/L. Assuming water consumption is as recommended, water containing 50-100 mg/L of calcium provides 5.4-12.8% of the recommended intake of calcium for children aged one to thirteen, up to 13.6% for adolescents, 5.8-17.6% for adults, and up to 20.8% for lactating mothers. Water with 100-150 mg/L of calcium provides 10 31% of the recommended dietary allowance, depending on the age of the individual. DISCUSSION: Public drinking water and natural mineral water consumption in a third of Spanish cities can be considered an important complementary source of calcium. PMID- 25137281 TI - There is chronic latent magnesium deficiency in apparently healthy university students. AB - INTRODUCTION: Magnesium is an essential micronutrient for human body, and its deficiency has been associated with risk of non-communicable diseases. OBJECTIVE: Assessment of magnesium status, and evaluation of the frequency of magnesium deficiency in a group of healthy adults. METHODS: Plasma and erythrocyte magnesium levels, and magnesium intake were determined in 115 students (55 women and 60 men), from a public university in Brazil. RESULTS: The medians of magnesium concentration in plasma (0.76 mmol/L), erythrocyte (1.97 mmol/L), and of dietary daily intake (8.84 mmol/d) were low. Forty two percent of participants had plasma or erythrocyte magnesium below the limit of 0.75 and 1.65 mmol/L, respectively. A high percentage showed high probability of inadequate magnesium intake. CONCLUSIONS: There was a high frequency of subclinical magnesium deficiency in the adults assessed, that could be related to low dietary magnesium intake. PMID- 25137283 TI - [Analysis of food service and opinion of its users in a Catalan prison]. AB - INTRODUCTION: Studies on food services are increasing actually in Spain. However, there still is very little information on how this service is organized in prisons, and even less about how it is perceived by its residents. OBJECTIVES: To analyze the food service and menu in the Modelo Prison in Barcelona, and confront it with the perception of prisoners. METHODS: Semi-structured open interview with an official of the Division of Prisons, participant observation in the dining room and other spaces by one of the study researchers, and a specifically designed questionnaire adapted to this kind of institution. Nutrition and menu quality assessment was performed using the DIAL program and healthy eating index (IAS). RESULTS: The supplied menus usually contain an excess of fat (41.3%) and carbohydrate deficit (41.7 %) even if is acceptable under IAS score (58.4 points). 75% of residents uses the dining room for daily main meals, spending less than 15 minutes on average per meal. The space is considered very noisy. The portions are considered adequate, but the taste, quality and service of food are negatively valued. DISCUSSION AND CONCLUSIONS: Some gaps between institutional proposals and everyday practices and perceptions of users are clearly denoted. Some changes in food and dishes served in the menus -such as reducing meat and increasing consumption of legumes- could contribute to improve nutrition, perception and final cost of the menu. A greater variety of food and more possibility of choice in the dining room and in the shop could be also positive. A strategic reorganization of the use of time and space in the dining room that would reduce the feeling of discomfort and noise could contribute to a better and more enjoyable use of it, while contributing to a better perception of food and welfare in general. PMID- 25137282 TI - Anthropometric, food intake differences and applicability of low-cost instruments for the measurement of body composition in two distinct groups of individuals with short bowel syndrome. AB - INTRODUCTION: Short bowel syndrome is associated with weight loss due to nutrient, electrolyte and fluid malabsorption. In view of the pathophysiology of SBS, all patients would be expected to exhibit similar clinical signs and symptoms, whereas many variations occur probably due to the adaptive capacity of the remaining small intestine in order to compensate for the resected area. OBJECTIVE: To determine whether there is a difference in nutritional status and food intake between patients receiving PNT, patients who do not receive PNT but are monitored on an ambulatory basis, and control subjects, and 2) to determine body composition by two different methods, i.e., electrical bioimpedance and skin fold measurement. METHODS: This was a case-control study where the subjects were divided into three groups: parenteral group (PG) - adults with a history of SBS intermittently using PNT; ambulatory group (AG) - adults with a history of SBS who do not receive PNT; control group (CG) - adults with no history of intestinal resections and/or use of PNT. The volunteers were submitted to measurements of body weight, height, body composition by bioimpedance analysis and assessment of food intake using a food frequency questionnaire. Univariate analysis of variance (ANOVA) with the aid of the SAS(r) 9.2. software, using the PROC GLM feature. The Student t-test was used to compare the instruments for the assessment of body composition, with the aid of the PROC TTEST feature of the SAS(r) 9.2 software. RESULTS: Thirty-two volunteers, 19 women and 13 men, participated in the study. The PNT group consisted of 9 volunteers, 4 women and 5 men, with a mean (+/- SD) age of 57 +/- 9 years. The nutrition status and food intake were different between the groups. There was no difference in percent body fat measured by anthropometry and bioimpedance analysis. DISCUSSION AND CONCLUSION: Large resections, as well as the resected portions, explain the greater nutritional impairment of PG compared to AG and CG, although no significant difference in food consumption was detected between these three groups. Since the use of PNT can lead to a state of hyperhydration, the results of BIA should be interpreted with caution, in view of the fact that the lean mass determined by this method varies positively with the hydration state of an individual. PMID- 25137284 TI - Development of type 2 diabetes mellitus thirty-one years after Billroth II in a patient asking for diabetes surgery. AB - INTRODUCTION: Diabetes surgery in obese and slim patients seems to be a superior alternative to the current medical treatment. Gastric bypass is an alternative treatment for diabetes. Nevertheless, there are still doubts whether diabetes can recur if you gain weight or if the effects are maintained over time. Other questions refer to the type of surgery to make the bypass limb length or reservoir size for the resolution of the Diabetes Mellitus. PRESENTATION OF CASE: Male patient 69-year-old came to us in order to perform tailored One Anastomosis Gastric Bypass (BAGUA) to treat his type 2 diabetes mellitus and metabolic syndrome. He has a history of peptic ulcer treated with subtotal gastrectomy and Billroth II reconstruction 49 years ago. He currently is not obese and developed diabetes 31 years after surgery. DISCUSSION: Globally there are no reports of patients with normal BMI that after performing gastric bypass developed diabetes mellitus. There are cases where obese diabetic patients after gastric bypass improve or remits the T2DM, but it relapses due to insufficient weight loss or gain it. The patient with gastric bypass Billroth II type, should not developed diabetes. He is normal weight and not had weight gain that could be linked to the development of diabetes. CONCLUSIONS: The results generated by bariatric surgery are encouraging, but still do not clarify the precise way how surgery produces rapid improvement of systemic metabolism as in diabetes, but in our patient, the effect was quite different because the gastric bypass had no protective effect against diabetes. PMID- 25137289 TI - The role of cervical and ocular vestibular evoked myogenic potentials in the assessment of patients with vestibular schwannomas. AB - OBJECTIVES: To investigate the clinical utility of VEMPs in patients suffering from unilateral vestibular schwannoma (VS) and to determine the optimal stimulation parameter (air conducted sound, bone conducted vibration) for evaluating the function of the vestibular nerve. METHODS: Data were obtained in 63 patients with non-operated VS, and 20 patients operated on VS. Vestibular function was assessed by caloric, cervical and ocular VEMP testing. 37/63 patients with conclusive ACS ocular VEMPs responses were studied separately. RESULTS: In the 63 non-operated VS patients, cVEMPs were abnormal in 65.1% of patients in response to AC STB and in 49.2% of patients to AC clicks. In the 37/63 patients with positive responses from the unaffected side, oVEMPs were abnormal in 75.7% of patients with ACS, in 67.6% with AFz and in 56.8% with mastoid BCV stimulation. In 16% of the patients, VEMPs were the only abnormal test (normal caloric and normal hearing). Among the 26 patients who did not show oVEMP responses on either side with ACS, oVEMPs responses could be obtained with AFz (50%) and with mastoid stimulation (89%). CONCLUSIONS: The VEMP test demonstrated significant clinical value as it yielded the only abnormal test results in some patients suffering from a unilateral vestibular schwannoma. For oVEMPs, we suggest that ACS stimulation should be the initial test. In patients who responded to ACS and who had normal responses, BCV was not required. In patients with abnormal responses on the affected side using ACS, BCV at AFz should be used to confirm abnormal function of the superior vestibular nerve. In patients who exhibited no responses on either side to ACS, BCV was the only approach allowing assessment of the function of the superior vestibular nerve. We favor using AFz stimulation first because it is easier to perform in clinical practice than mastoid stimulation. PMID- 25137290 TI - A multimeric MR-optical contrast agent for multimodal imaging. AB - We describe the design, synthesis and in vitro evaluation of a multimodal and multimeric contrast agent. The agent consists of three macrocyclic Gd(III) chelates conjugated to a fluorophore and possesses high relaxivity, water solubility, and is nontoxic. The modular synthesis is amenable for the incorporation of a variety of fluorophores to generate molecular constructs for a number of applications. PMID- 25137291 TI - A cotton (Gossypium hirsutum) gene encoding a NAC transcription factor is involved in negative regulation of plant xylem development. AB - NAC proteins that compose of one large family of plant specific transcription factors (TF) play the important roles in many biological processes (such as morphogenesis, development, senescence and stress signal transduction). In this study, a gene (designated as GhXND1) encoding a NAC transcription factor was identified in cotton. Sequence analysis indicated that GhXND1 gene contains two introns inserted in its open reading frame (ORF). GhXND1 protein is localized in the cell nucleus, and displays the transactivation activity. GhXND1 transcripts were mainly detected in cotyledons, petals, roots, hypocotyls and stems, but little or no signals of GhXND1 expression were found in the other tissues. Ectopic expression of GhXND1 in Arabidopsis resulted in a reduction in number of xylem vessel cells and cell wall thickness of interfascicular fibers in the transgenic plants, compared with those of wild type. And expression of some cell wall biosynthesis-related genes was down-regulated in the GhXND1 transgenic plants. Collectively, the data presented in this study suggested that GhXND1 may be involved in regulation of plant xylem development. PMID- 25137292 TI - Molecular characterization and expression analysis of the critical floral genes in hickory (Carya cathayensis Sarg.). AB - The full ORFs of three floral genes in hickory (Carya cathayensis Sarg.), CcAGL24 (the AGAMOUS-LIKE24 homolog), CcSOC1 (the SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 homolog) and CcAP1 (the APETALA1 homolog) are derived using a 5' RACE PCR protocol. Through sequence alignment and phylogenetic analysis, it is demonstrated that the three genes belong to the MADS-Box family. According to the evolutionary trees of the three genes, the homologous genes from the same family cluster well together, while those from different orders doesn't match evolutionary regularity of individual organisms. The result of Quantitative RT PCR analysis shows that the transcriptional levels of the three genes are up regulated in early stage and down-regulated in late stage in pistillate floral development. However, it takes different time to reach respective expression peak among the three genes. In staminate floral development, the transcription trend of the three genes is up-regulated, subsequently down-regulated, and then up regulated again. Nevertheless, those trajectories, peaks, expression levels, inflection points are different in pistillate floral development. The result suggests that their functions are different in between pistillate and staminate floral development. The probable ordinal site of the three genes in the flowering network from top down is CcAGL24, CcSOC1, and CcAP1, which is identical to that in herbaceous plants. Moreover, several adverse environmental factors trigger several negative genes and then confine the development of staminate floral buds. Our results suggest the possible relationship among the three critical floral genes and their functions throughout the floral development in hickory. PMID- 25137294 TI - Nano-titanium dioxide bioreactivity with human alveolar type-I-like epithelial cells: Investigating crystalline phase as a critical determinant. AB - There can be significant variability between bioreactivity studies of nanomaterials that are apparently the same, possibly reflecting differences in the models used and differing sources of experimental material. In this study, we have generated two crystal forms of titanium dioxide nanoparticles (nano-TiO2), pure anatase and pure rutile to address the hypothesis that the bioreactivity of these nanoparticles with human alveolar epithelium will depend on their crystal phase. We used a human alveolar type-I-like epithelial cell model (TT1; generated in-house from primary human alveolar epithelial type II cells); these cells cover 95% of the alveolar epithelial surface area and are an important target cell for inhaled nanomaterials. Using literature as a guide, we hypothesised that pure anatase nano-TiO2 would display greater bioreactivity with TT1 cells in comparison to pure rutile nano-TiO2. However, we found the profile and pattern of inflammatory mediator release was similar between these two nano-TiO2 formats, although pure rutile treatment caused a small, but consistently greater, response for IL-6, IL-8 and MCP-1. Interestingly, the temporal induction of oxidative stress (increased reactive oxygen species levels and depleted glutathione) varied markedly between the different nano-TiO2 formats. We have shown that a combination of using nanomaterials synthesised specifically for toxicological study and the use of a highly relevant, reproducible human lung cell model, offers a useful approach to delineating the physicochemical properties of nanomaterials that may be important in their cellular reactivity. PMID- 25137293 TI - Activation-induced cell death drives profound lung CD4(+) T-cell depletion in HIV associated chronic obstructive pulmonary disease. AB - RATIONALE: As overall survival improves, individuals with HIV infection become susceptible to other chronic diseases, including accelerated chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine whether individuals with HIV associated COPD exhibit dysregulated lung mucosal T-cell immunity compared with control subjects. METHODS: Using flow cytometry, we evaluated peripheral blood and lung mucosal T-cell immunity in 14 HIV(+)COPD(+), 13 HIV(+)COPD(-), and 7 HIV(-)COPD(+) individuals. MEASUREMENTS AND MAIN RESULTS: HIV(+)COPD(+) individuals demonstrated profound CD4(+) T-cell depletion with reduced CD4/CD8 T cell ratios in bronchoalveolar lavage-derived lung mononuclear cells, not observed in peripheral blood mononuclear cells, and diminished CD4(+) T cell absolute numbers, compared with control subjects. Furthermore, HIV(+)COPD(+) individuals demonstrated decreased pulmonary HIV-specific and staphylococcal enterotoxin B-reactive CD4(+) memory responses, including loss of multifunctionality, compared with HIV(+)COPD(-) control subjects. In contrast, lung mucosal HIV-specific CD8(+) T-cell responses were preserved. Lung CD4(+) T cells from HIV(+)COPD(+) individuals expressed increased surface Fas death receptor (CD95) and programmed death-1, but similar bronchoalveolar lavage viral loads as control subjects. However, programmed death-1 expression inversely correlated with HIV-specific lung CD4(+)IFN-gamma(+) T-cell responses, suggesting functional exhaustion. Moreover, lung CD4(+) T cells from HIV(+)COPD(+) patients demonstrated increased basal and HIV antigen-induced expression of the early apoptosis marker annexin V compared with control subjects, which was significantly attenuated with anti-Fas blockade. Lastly, lung mucosal, but not blood, CD4(+)/CD8(+) ratios from HIV(+) patients significantly correlated with the FEV1, but not in HIV(-)COPD(+) patients. CONCLUSIONS: Together, our results provide evidence for profound lung mucosal CD4(+) T-cell depletion via a Fas dependent activation-induced cell death mechanism, along with impaired HIV specific CD4(+) immunity as immunologic features of HIV-associated COPD. PMID- 25137295 TI - Inhibition of potential uptake pathways for silver nanoparticles in the estuarine snail Peringia ulvae. AB - Mechanisms involved in the uptake of Ag NPs, and NPs in general, have been long debated within nano-ecotoxicology. In vitro studies provide evidence of the different available uptake pathways, but in vivo demonstrations are lacking. In this study, pharmacological inhibitors were employed to block specific uptake pathways that have been implicated in the transport of metal NPs and aqueous metal forms; phenamil (inhibits Na(+) channel), bafilomycin A1 (H(+) proton pump), amantadine (clathrin-mediated endocytosis), nystatin (caveolae-mediated endocytosis) and phenylarsine oxide (PAO, macropinocytosis). Peringia ulvae (snails) were exposed to 150 ug Ag L(-1) added as citrate capped Ag NPs or aqueous Ag (AgNO3) in combination with inhibitor treatment (determined by preliminary studies). Reductions in accumulated tissue burdens caused by the inhibitors were compared to control exposures (i.e. no inhibition) after 6 and 24 h. No inhibitor treatment completely eliminated the uptake of Ag in either aqueous or NP form, but all inhibitor treatments, except phenamil, significantly reduced the uptake of Ag presented as Ag NPs. Clathrin- and caveolae-mediated endocytosis appear to be mechanisms exploited by Ag NPs, with the latter pathway only active at 24 h. Inhibition of the H(+) proton pump showed that a portion of Ag NP uptake is achieved as aqueous Ag and is explained by the dissolution of the particles (~25% in 24 h). This in vivo study demonstrates that uptake of Ag from Ag NPs is achieved by multiple pathways and that these pathways are simultaneously active. PMID- 25137296 TI - Assessing orally bioavailable commercial silver nanoparticle product on human cytochrome P450 enzyme activity. AB - Nanotechnology produces a wide range of medicinal compounds, including nanoparticulate silver, which are increasingly introduced in various forms for consumer use. As with all medicinal compounds, potential drug interactions are an important consideration for ingested silver nanoparticles. Nanoparticulate silver drug interactions may be mediated through induced oxidative stress in liver tissue where the majority of systemically bioavailable silver nanoparticles is found. To investigate whether an orally ingested commercially available colloidal silver nanoproduct produces pharmacokinetic interference on select cytochrome P450 enzymes, a prospective, single-blind, controlled in vivo human study using simultaneous administration of standardized probes for P450 enzyme classes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was conducted. Oral ingestion of a commercial colloidal silver nanoproduct produces detectable silver in human serum after 14 days of dosing. This silver, however, elicits no demonstrable clinically significant changes in metabolic, hematologic, urinary, physical findings or cytochrome P450 enzyme inhibition or induction activity. Given their increasingly broad, diverse human exposures, future characterization of human cytochrome P450 enzyme activity for other systemically bioavailable nanotechnology products are warranted. PMID- 25137297 TI - Use of ultrasound for lower extremity. AB - PURPOSE OF REVIEW: To explore the recent advances in the use of ultrasound for lower extremity blocks, including approaches to the lumbar and sacral plexus blocks. RECENT FINDINGS: Procedures of the lower extremity often require blocks of the lumbar and sacral plexuses. The use of ultrasound offers some advantages, including the possibility to directly visualize the distribution of local anesthetics. SUMMARY: Lower extremity blocks under ultrasound guidance often require advanced skills because of the depth of target nerves. This review summarizes the recent advances in the use of ultrasound guidance over traditional techniques. PMID- 25137298 TI - How to give a scientific talk, present a poster, and write a research paper or proposal. PMID- 25137299 TI - Improved early performance of turkey poults given an Aloe ferox leaf extract with bentonite. AB - AT-402 (20 g/kg), a proprietary blend of Aloe ferox leaf extract and calcium bentonite, had no adverse effect on poult body weights at 3 weeks of age. Lower body weights and lower feed consumption were observed in 4-week-old poults given 10 and 20 g/kg of AT-402 compared to poults given 0 or 5 g/kg. Floor-reared poults, given either 5 or 10 g/kg AT-402 to 4 weeks of age, were significantly heavier than controls (0 g/kg AT-402), and feed conversion ratios for AT-402 given poults were improved. Xylose uptake in 5 g/kg AT-402-fed poults was significantly greater than in poults given AT-402 at 0 and 10 g/kg, reflecting increased body weights of 5 g/kg AT-402-fed poults. Delayed access by poults to the AT-402 until 10 d of age also improved 4-week body weights, suggesting that the AT-402 might improve performance as soon as it is given. AT-402 at 5 g/kg was most efficacious as demonstrated by improved body weights and feed conversions. PMID- 25137301 TI - Nitrogen self-doped porous carbon from surplus sludge as metal-free electrocatalysts for oxygen reduction reactions. AB - Nitrogen self-doped porous carbon was prepared by calcination treatment of surplus sludge, a toxic byproduct from microbial wastewater treatments, and exhibited a mesoporous structure, as manifested in scanning and transmission electron microscopic measurements. Nitrogen adsorption/desorption studies showed that the porous carbon featured a BET surface area as high as 310.8 m(2)/g and a rather broad range of pore size from 5 to 80 nm. X-ray photoelectron spectroscopic studies confirmed the incorporation of nitrogen into the graphitic matrix forming pyridinic and pyrrolic moieties. Interestingly, the obtained porous carbon exhibited apparent electrocatalytic activity in oxygen reduction in alkaline media, with the optimal temperatures identified within the range of 600 to 800 degrees C, where the number of electron transfers involved in oxygen reduction was estimated to be 3.5 to 3.7 and the performance was rather comparable to leading literature results as a consequence of deliberate engineering of the graphitic matrix by nitrogen doping. PMID- 25137300 TI - Bariatric surgery improves the cavernosal neuronal, vasorelaxation, and contraction mechanisms for erectile dysfunction as result of amelioration of glucose homeostasis in a diabetic rat model. AB - BACKGROUND: Bariatric surgery is an effective treatment option for both obesity and obesity-related type 2 diabetes mellitus (T2DM). However, little is known regarding the effects of bariatric surgery on erectile dysfunction among patients with T2DM. Therefore, we investigated whether bariatric surgery would lead to structural and biochemical changes in the corpus cavernosum. MATERIAL AND METHOD: Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a control group (sham operation, n = 10) or a bariatric surgery group (gastric bypass surgery, n = 15). Four weeks after the operation, each group of rats was evaluated with an oral glucose tolerance test (OGTT). The penile intracavernous pressure was measured for erectile functional analysis. Histologic evaluation of the tissue was performed with Masson's trichrome staining. Endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Rho kinase, and 8 hydroxy-2-deoxyguanosine (8-OHdG) levels in the corpus cavernosum were assayed by using western blot and ELISA. RESULTS: The mean body weight of the bariatric surgery group was lower than the control group (p = 0.002). The postoperative OGTT result was lower in the bariatric surgery group than in the control group (p = 0.014), and this was lower than the preoperative value (p = 0.037). The intracavernous pressure/mean arterial pressure ratio was higher in the bariatric surgery group compared to the control group (p = 0.021), and a higher cavernosum smooth muscle/collagen ratio was observed in the bariatric surgery group compared to the control group (p = 0.025). Likewise, the expression of eNOS and nNOS was higher in bariatric surgery group than in the control group (p = 0.027 and p = 0.008, respectively). Decreased expression of Rho kinase and levels of 8-OHdG were observed in the bariatric surgery group (p = 0.032). CONCLUSION: In this animal model, bariatric surgery appears to ameliorate T2DM-related metabolic dysfunction leading to structural and biochemical changes in the corpus cavernosum, and thus, results in improvement of erectile dysfunction associated with T2DM. PMID- 25137302 TI - Measuring bacterial adaptation dynamics at the single-cell level using a microfluidic chemostat and time-lapse fluorescence microscopy. AB - We monitored the dynamics of cell dimensions and reporter GFP expression in individual E. coli cells growing in a microfluidic chemostat using time-lapse fluorescence microscopy. This combination of techniques allows us to study the dynamical responses of single bacterial cells to nutritional shift-down or shift up for longer times and with more precision over the chemical environment than similar experiments performed on conventional agar pads. We observed two E. coli strains containing different promoter-reporter gene constructs and measured how both their cell dimensions and the GFP expression change after nutritional upshift and downshift. As expected, both strains have similar adaptation dynamics for cell size rearrangement. However, the strain with a ribosomal RNA promoter dependent reporter has a faster GFP production rate than the strain with a constitutive promoter reporter. As a result, the mean GFP concentration in the former strain changes rapidly with the nutritional shift, while that in the latter strain remains relatively stable. These findings characterize the present microfluidic chemostat as a versatile platform for measuring single-cell bacterial dynamics and physiological transitions. PMID- 25137305 TI - [Individualised parent counselling in paediatric practices for the reduction of second-hand smoke exposure of their children: a feasibility study]. AB - AIM: The aim of this study was to test the feasibility of a web-based programme provided by paediatric practices for counselling parents to reduce second-hand smoke exposure of their children. METHODS: Accompanying persons of children were systematically screened concerning tobacco smoking at their home in 2 Swiss paediatric practices. They were invited for programme participation if they or their partners smoked at home regularly. The web-based programme provided at least 1 computer-tailored counselling letter. Upto 3 additional counselling letters could be requested online by the participants over a period of 3 months. The letters were tailored according to the indoor smoking behaviour of the parents and considered individual barriers and resources for the establishment of a smoke-free home. Additionally, further information and advice could be requested on the programme website. Feasibility indicators were the participation rate, programme use, and programme evaluation by the participants. RESULTS: 3 055 (82.3%) of 3 712 accompanying persons of children in the paediatric practices were screened concerning tobacco smoking at their home. 96 (56.8%) of 169 eligible persons participated in the programme. 68 (70.8%) of the 96 programme participants could be reassessed at post assessment. 9 (15.0%) of 60 participants who provided a valid e-mail address requested more than one counselling letter. The counselling letters and the web-based programme were evaluated positively by the programme participants. CONCLUSION: Systematic screening combined with the provision of individually tailored counselling letters for parents to reduce second-hand smoke exposure of their children was feasible in paediatric practices. Possible strategies to in-crease the use and reach of the programme are -discussed. PMID- 25137306 TI - [Ambulatory care-sensitive conditions in Germany: a small area analysis (2006 2009)]. AB - PURPOSE: The paper aims (1) to identify and depict cartographically ambulatory care-sensitive conditions in Germany (based on data for the years 2006-2009) and (2) to discuss the implications. METHOD: The selection of ambulatory care sensitive conditions (ACSC) was based on a literature review by Purdy et al. (2009) because a German catalogue of ACSC does not yet exist. Five of these indications were excluded due to limited data -access or a low number of cases. Additionally, 2 -diagnoses that are potentially relevant for Germany were included. Subsequently, diagnosis-specific hospitalisation rates were calculated for each of the 412 counties (Stadtkreise and Landkreise). The spatial distribution of 6 selected diag-noses (heart failure, diabetes, dehydration and gastroenteritis, ENT infections, influenza and pneumonia as well as schizophrenia) was depicted and discussed. Furthermore, an overall analysis of diagnoses analysis was performed. RESULTS: Based on the overall analysis, counties with high hospitalisation rates were identified in Mecklenburg-Western Pomerania, Saxony-Anhalt and Thuringia as well as to a lesser degree in Brandenburg, Saarland, Rhineland Palatinate and North Rhine-Westphalia (for men and women). Low hospitalisation rates were often present in counties in Baden Wuerttemberg. Based on the diagnosis-specific analysis, some regional clusters could be identified. Thus, high hospitalisa-tion rates for heart failure, diabetes, ENT infections were especially present in Eastern Germany. In contrast, there were no distribution patterns for high hospitalisation rates due to influenza and pneumonia. However, differences could be also identified between rural and urban regions: while hospitalisations due to dehydration and gastroenteritis were more often in rural -districts, hospitalisations due to schizophrenia occurred more frequently in urban regions. CONCLUSION: Knowledge of the spatial distribution of ACSC -rates serves as an important indicator for the identification of districts where health-care quality and access (structural- related) can be optimised. The analysis of hospitalisation rates for 6 selected indications showed that for some indications there were clear regional differences in the distribution of ACSCs in -Germany. PMID- 25137307 TI - [Specialised out-patient palliative care (SAPV) in Bavaria: efficiency, structural and process-related effects and rural care]. AB - Empirical indications show that specialised out-patient palliative care (SAPV), introduced in Germany in 2007, allows critically ill and dying patients to pass away within their own home even under complex symptoms. SAPV avoids emergency and hospital interferences, and the patient's wish to stay at home until the very end can be respected in most cases. The performance of SAPV is not solely focused on medical and patient-care aspects. It includes consulting and coordination work and also psycho-social support both of patients and family members. Within this framework, different active factors could be identified that are essential for high-quality care. Furthermore, the results show that the general ambulant care commodities on site determine the need, the extent and even the efficiency of SAPV. At the same time, SAPV changes also the respective care environment: it changes the roles of previous care providers and offers new resources, though not all existing resources (e. g., hospice services) are taken into account. PMID- 25137304 TI - Serum nutritional biomarkers and their associations with sleep among US adults in recent national surveys. AB - BACKGROUND: The associations between nutritional biomarkers and measures of sleep quantity and quality remain unclear. METHODS: Cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) 2005-2006 were used. We selected 2,459 adults aged 20-85, with complete data on key variables. Five sleep measures were constructed as primary outcomes: (A) Sleep duration; (B) Sleep disorder; (C) Three factors obtained from factor analysis of 15 items and labeled as "Poor sleep-related daytime dysfunction" (Factor 1), "Sleepiness" (Factor 2) and "Sleep disturbance" (Factor 3). Main exposures were serum concentrations of key nutrients, namely retinol, retinyl esters, carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein+zeaxanthin, lycopene), folate, vitamin B-12, total homocysteine (tHcy), vitamin C, 25-hydroxyvitamin D (25(OH)D) and vitamin E. Main analyses consisted of multiple linear, logistic and multinomial logit models. RESULTS: Among key findings, independent inverse associations were found between serum vitamin B-12 and sleep duration, 25(OH)D and sleepiness (as well as insomnia), and between folate and sleep disturbance. Serum total carotenoids concentration was linked to higher odds of short sleep duration (i.e. 5-6 h per night) compared to normal sleep duration (7-8 h per night). CONCLUSIONS: A few of the selected serum nutritional biomarkers were associated with sleep quantity and quality. Longitudinal studies are needed to ascertain temporality and assess putative causal relationships. PMID- 25137308 TI - [Assistive Services in the Workplace of People with Hearing Impairment in the State of North Rhine-Westphalia]. AB - AIM OF THE STUDY: Assistive services in the workplace are an important aspect of the participation of people with hearing impairment in working life. This article presents the results of the GINKO study and an survey conducted by the University of Cologne on behalf of the MAIS in order to provide a comprehensive examination of the employment situation of hearing impaired people in North Rhine-Westphalia. The GINKO study examines the impact of laws on the integration of hard-of-hearing and deaf people as well as people who have become deaf as adults, focusing on communication and organizations; this project was funded by the German Federal Ministry for Labour and Social Affairs (BMAS). METHOD: In the GINKO study, conducted in cooperation with the German Association of the Hard of Hearing and the German Association of the Deaf, a standardised questionnaire with questions about the workplace was administered to employed people with hearing impairments. The questionnaire was administered on paper and was also available online accompanied by sign language videos. The University of Cologne study in North Rhine-Westphalia examined the service situation of hard-of-hearing, deaf and deaf blind people through face-to-face interviews and government statistics. RESULTS: The results of the nationwide GINKO study show that hearing-impaired people in North Rhine-Westphalia draw on assistive services in employment more often than hearing-impaired people in the rest of Germany. The study found statistically significant differences in the categories of "maintenance and development of professional knowledge and skills" and "psychosocial support in conflict situations resulting from disability". CONCLUSION: One reason for the more positive evaluations of the participants in North Rhine-Westphalia as compared to other regions in Germany could be the particular network of support services in that state. However, the overall positive results from North Rhine-Westphalia should not obscure the fact that a majority of participants in many areas of North Rhine-Westphalia reported much less positive evaluations. They reported that they did not (yet) have an accessible workplace and that assistive services are not available to all hearing impaired workers. PMID- 25137309 TI - Association of NCAM1 polymorphisms with autism and parental age at conception in a Chinese Han population. AB - AIMS: The neural cell adhesion molecule (NCAM) has been reported to be involved in the development of the central nervous system and its mRNA level might decrease in the serum of autistic patients. However, there was no evidence of the association of the NCAM1 gene polymorphisms with autism. In the present study, we enrolled 237 children with autism and 451 healthy control subjects. Then, we used the direct DNA sequencing for genotyping five tag single-nucleotide polymorphisms (SNPs) in the NCAM1 gene. RESULTS: By using case-control association analyses, we found that three SNPs at the NCAM1 gene were associated with autism (rs 4937786, p=0.015; rs 12418058, p=0.0076; rs 1436109, p=0.0023). Two of them remained significant after the Bonferroni multiple testing correction (rs 12418058, P(corrected) =0.038; rs 1436109, P(corrected) =0.012). Moreover, two of the SNPs were associated with the parental age at conception in autism (rs 12418058, p=0.037; rs 1436109, p=0.01). CONCLUSION: These results showed that NCAM1 might play an important role in the pathogenesis of autism. PMID- 25137310 TI - Enantioselective olefin metathesis with cyclometalated ruthenium complexes. AB - The success of enantioselective olefin metathesis relies on the design of enantioenriched alkylidene complexes capable of transferring stereochemical information from the catalyst structure to the reactants. Cyclometalation of the NHC ligand has proven to be a successful strategy to incorporate stereogenic atoms into the catalyst structure. Enantioenriched complexes incorporating this design element catalyze highly Z- and enantioselective asymmetric ring opening/cross metathesis (AROCM) of norbornenes and cyclobutenes, and the difference in ring strain between these two substrates leads to different propagating species in the catalytic cycle. Asymmetric ring closing metathesis (ARCM) of a challenging class of prochiral trienes has also been achieved. The extent of reversibility and effect of reaction setup was also explored. Finally, promising levels of enantioselectivity in an unprecedented Z-selective asymmetric cross metathesis (ACM) of a prochiral 1,4-diene was demonstrated. PMID- 25137311 TI - Trait-specific responses of wild bee communities to landscape composition, configuration and local factors. AB - Land-use intensification and loss of semi-natural habitats have induced a severe decline of bee diversity in agricultural landscapes. Semi-natural habitats like calcareous grasslands are among the most important bee habitats in central Europe, but they are threatened by decreasing habitat area and quality, and by homogenization of the surrounding landscape affecting both landscape composition and configuration. In this study we tested the importance of habitat area, quality and connectivity as well as landscape composition and configuration on wild bees in calcareous grasslands. We made detailed trait-specific analyses as bees with different traits might differ in their response to the tested factors. Species richness and abundance of wild bees were surveyed on 23 calcareous grassland patches in Southern Germany with independent gradients in local and landscape factors. Total wild bee richness was positively affected by complex landscape configuration, large habitat area and high habitat quality (i.e. steep slopes). Cuckoo bee richness was positively affected by complex landscape configuration and large habitat area whereas habitat specialists were only affected by the local factors habitat area and habitat quality. Small social generalists were positively influenced by habitat area whereas large social generalists (bumblebees) were positively affected by landscape composition (high percentage of semi-natural habitats). Our results emphasize a strong dependence of habitat specialists on local habitat characteristics, whereas cuckoo bees and bumblebees are more likely affected by the surrounding landscape. We conclude that a combination of large high-quality patches and heterogeneous landscapes maintains high bee species richness and communities with diverse trait composition. Such diverse communities might stabilize pollination services provided to crops and wild plants on local and landscape scales. PMID- 25137312 TI - An abnormal N-heterocyclic carbene-carbon dioxide adduct from imidazolium acetate ionic liquids: the importance of basicity. AB - In the reaction of 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc] ionic liquid with carbon dioxide at 125 degrees C and 10 MPa, not only the known N heterocyclic carbene (NHC)-CO2 adduct I, but also isomeric aNHC-CO2 adducts II and III were obtained. The abnormal NHC-CO2 adducts are stabilized by the presence of the polarizing basic acetate anion, according to static DFT calculations and ab initio molecular dynamics studies. A further possible reaction pathway is facilitated by the high basicity of the system, deprotonating the initially formed NHC-CO2 adduct I, which can then be converted in the presence of the excess of CO2 to the more stable 2-deprotonated anionic abnormal NHC-CO2 adduct via the anionic imidazolium-2,4-dicarboxylate according to DFT calculations on model compounds. This suggests a generalizable pathway to abnormal NHC complex formation. PMID- 25137313 TI - Microextraction by packed sorbent liquid chromatography with time-of-flight mass spectrometry of triazines employing a molecularly imprinted polymer. AB - Molecularly imprinted polymers for the determination of triazines were synthesized by precipitation using atrazine as template, methacrylic acid as functional monomer, ethylene glycol dimethacrylate as crosslinker, and 2,2' azobisisobutrynitrile as initiator. The polymers were characterized by infrared spectroscopy and scanning electron microscopy and packed in a device for microextraction by packed sorbent aiming for the preconcentration/cleanup of herbicides, such as atrazine, simazine, simetryn, ametryn, and terbutryn in corn samples. Liquid chromatography coupled with time-of-flight mass spectrometry was used for the separation and determination of the herbicides. The selectivity coefficient of molecularly imprinted polymers was compared with that of nonimprinted polymer for the binary mixtures of atrazine/propanil and atrazine/picloram, and the values obtained were 15.6 and 2.96, respectively. The analytical curve ranged from 10 to 80 MUg/kg (r = 0.989) and the limits of detection and quantification in the corn matrices were 3.3 and 10 MUg/kg, respectively. Intra- and interday precisions were < 14.8% and accuracy was better than 90.9% for all herbicides. Polymer synthesis was successfully applied to the cleanup and preconcentration of triazines from fortified corn samples with 91.1 109.1% of recovery. PMID- 25137316 TI - [Procalcitonin as a marker of the postoperative infection in cardiovascular surgery]. AB - BACKGROUND: Procalcitonin( PCT) is a new diagnostic marker of severe bacterial infection and sepsis. PURPOSE: To evaluate the usefulness of PCT in patients with suspicion of bacterial infection after cardiovascular surgery. METHODS: From January 2012 to December 2012, 150 consecutive patients after cardiovascular surgery were studied retrospectively. Postoperative infection was diagnosed under Centers for Disease Control and Prevention (CDC) guideline for healthcare associated infection, and biomarker levels and microbiological specimen were evaluated. RESULTS: Only blood stream infection group revealed higher PCT levels( median 5.0 ng/ml) than non blood stream infection group( median 0.1 ng/ml)[p<0.01]. CONCLUSION: PCT is the best biomarker available for the clinical diagnosis of blood stream infection after cardiovascular surgery. PMID- 25137318 TI - [Determinants of prolonged mechanical ventilation after cardiac surgery]. AB - PURPOSE: This study aimed to examine factors that delay weaning from ventilation after cardiac surgery. METHODS: A retrospective examination was made on 1,033 patients who had undergone cardiac surgery through a midsternal incision between January 2009 and July 2011. The items examined were duration of postoperative ventilation, patient's background, and other surgical information. If patients were weaned within 24 hours from intensive care unit (ICU) admission, they were included in the timely weaning group. If patients required 24 hours or more to be weaned, they were included in the delayed weaning group. RESULTS: There was a relationship between prolonged ventilation and the following factors: emergency surgery, history of arrhythmia, history of motor system disorder, preoperative estimated glomerular filtration rate (eGFR), preoperative New York Heart Association (NYHA) classification, preoperative left ventricular ejection fraction (LVEF), operative method, operative time, blood loss, intraoperative fluid management, and number of days from surgery until achievement of independent gait. The independent factors delaying extubation were emergency surgery, preoperative NYHA classification, preoperative LVEF, operative method, operative time, blood loss, and intraoperative fluid management(p<0.05). CONCLUSION: Surgical invasiveness and preoperative heart failure were involved in the prolonged ventilation after cardiac surgery. PMID- 25137314 TI - Increased microstructural white matter correlations in left, but not right, temporal lobe epilepsy. AB - Microstructural white matter tract correlations have been shown to reflect known patterns of phylogenetic development and functional specialization in healthy subjects. The aim of this study was to establish intertract correlations in a group of controls and to examine potential deviations from normality in temporal lobe epilepsy (TLE). We investigated intertract correlations in 28 healthy controls, 21 left TLE (LTLE) and 23 right TLE (RTLE). Nine tracts were investigated, comprising the parahippocampal fasciculi, the uncinate fasciculi, the arcuate fasciculi, the frontoparietal tracts, and the fornix. An abnormal increase in tract correlations was observed in LTLE, while RTLE showed intertract correlations similar to controls. In the control group, tract correlations increased with increasing fractional anisotropy (FA), while in the TLE groups tract correlations increased with decreasing FA. Cluster analyses revealed agglomeration of bilateral pairs of homologous tracts in healthy subjects, with such pairs separated in our LTLE and RTLE groups. Discriminant analyses aimed at distinguishing LTLE from RTLE, revealing that tract correlations produce higher rates of accurate group classification than FA values. Our results confirm and extend previous work by showing that LTLE compared to RTLE patients display not only more extensive losses in microstructural orientation but also more aberrant intertract correlations. Aberrant correlations may be related to pathologic processes (i.e., seizure spread) or to adaptive processes aimed at preserving key cognitive functions. Our data suggest that tract correlations may have predictive value in distinguishing LTLE from RTLE, potentially moving diffusion imaging to a place of greater prominence in clinical practice. PMID- 25137319 TI - [Intravascular papillary endothelial hyperplasia of the lung]. AB - We report a rare case of pulmonary intravascular papillary endothelial hyperplasia. The patient was a 63-year-old male. Multiple lung nodules were noted on chest computed tomography( CT) at preoperative check for gastric cancer. Metastatic lung tumor was suspected, and partial resection of the right lung was performed. Histopathologic examination revealed papillary proliferation lined by endothelial cells and a hematoma. Immunohistochemically, the endothelial cells were positive for CD31/CD34 and factor VIII related antigen. PMID- 25137321 TI - [New prosthesis implant technique of aortic root abscess; circumferential transmural sutures]. AB - A patient with aortic root abscess was successfully treated with a newly developed suture technique named "circumferential transmural sutures". This suture technique provides 1)a tight attachment of the prosthesis to the aortic wall and 2)a secure healing of infection by exposure of the abscess cavity to blood flow without complicated procedures. This technique would be a useful alternative for the aortic root abscess without left ventriculo-aortic disruption. PMID- 25137322 TI - [Initial report of uniportal video-assisted thoracoscopic lobectomy in Japan]. AB - To date, more than 100 reports of several major pulmonary resections through a uniportal approach have been published. However, there have been no reports of uniportal thoracoscopic lobectomy in Japan. We present herein a successful case of uniportal thoracoscopic right lower lobectomy through a 3.5-cm incision for 84 year-old female patient with primary lung cancer (clinical stage I A). Postoperative course was uneventful and she discharged from the hospital on day 5 postoperatively. Pathological diagnosis was primary adenocarcinoma of T1aN0M0, stage I A. PMID- 25137323 TI - [Pediatric case of congenital coronary artery fistula; surgical result and late changes in coronary artery aneurysm]. AB - Congenital coronary artery fistula is an uncommon heart anomaly involving the coronary arteries. We report here a case of a 4-year-old boy who had a coronary fistula from the right coronary artery to the right ventricle, with a coronary aneurysm. He was asymptomatic, but the calculated ratio of pulmonary blood flow to systemic blood flow was shown to be high [pulmonary flow (Qp)/systemic flow(Qs)=1.78]. The coronary angiography showed that the right coronary artery was dilated beginning at the ostium and had an aneurysm at the acute marginal portion. A large spherical aneurysm approximately 20 mm in diameter was found to have been connected with coronary fistula opening into the right ventricle. Surgical repair by closure of the fistula under direct vision, partial resection and suture closure of the aneurysm was performed. Plication of the proximal portion of the right coronary artery was not performed, and the diffusely dilated artery was left untouched. After this operation, he recovered well under anticoagulant treatment with warfarin and aspirin. Postoperative angiography was performed 17 months after the surgery to evaluate morphological changes in the coronary artery. The angiography confirmed the closure of the fistula and the regression of coronary artery dilatation. PMID- 25137324 TI - [Pulmonary non-tuberculous mycobacteriosis complicated with lung cancer]. AB - A 54-year-old man with pulmonary non-tuberculous mycobacteriosis( pulmonary NTM) who had been treated by antituberculous chemotherapy, developed a new nodule of 1.3 cm in size in the segment 1/2 of the right upper lobe. The cavity of 3.5 cm in size in the segment 6 of the right lower lobe from which Mycobacterium intracellulare was bronchoscopically detected, was suspected to be pulmonary NTM lesion. Since lung cancer was highly suspected by radiological examinations, right upper lobectomy and S6 segmentectomy were performed. Pathological diagnosis for the right upper lobe nodule was adenocarcinoma. PMID- 25137325 TI - [Pulmonary actinomycosis that was difficult to make an accurate diagnosis]. AB - A 35-year-old man was referred to our hospital, because of recurrent pneumonia. His chest X-ray film and computed tomography showed mass-like consolidation with a cavity in the right upper lobe. He underwent a bronchoscopic examination, but no diagnosis was established. Therefore a surgical biopsy was performed, but the pathological findings revealed that it was only an inflammatory change without any malignant component. For a while, antibiotic and the steroid treatment was continued resulting in the aggravation of clinical findings. Finally, an upper lobe excision was performed for the complete excision of the lesion. As a result of pathology, pulmonary actinomycosis was diagnosed. PMID- 25137326 TI - [Purtscher's retinopathy following blunt chest compression]. AB - Following chest or abdominal injury, acute blurring of vision occurs without direct eye injury. This disease is known as Purtscher's retinopathy. A 74-year old man suffered blunt chest injury by air bag inflation at traffic accident. Next morning, he suddenly complained of visual abnormality. An ophthalmoscopy revealed multiple cotton-wool exudation and retinal edema. He was diagnosed as Purtscher's retinopathy. The symptoms of soft exudation and retinal edema gradually resolved. The visual acuity gradually improved, but not reached to the previous level. We must be aware of this retinopathy, since this is rare but sometimes sight-threatening condition. PMID- 25137330 TI - [Successful excision of a left ventricular fibroma in an adult patient; report of a case]. AB - A 55-year-old man was referred with a diagnosis of a left ventricular thrombus. Echocardiography revealed that he had a thrombus in the free wall of the left ventricle. Under cardiopulmonary bypass, we removed the intramural tumor. After the removal, the defect was repaired by Dor operation. Pathological examination revealed the tumor was a cardiac fibroma. He is doing well without any troubles 3 years after the operation. PMID- 25137331 TI - [Adult endocardial blood cyst; report of a case]. AB - We report herein a rare case of endocardial blood cyst (EBC) in an adult patient. A 63-year-old asymptomatic woman underwent echocardiography, which incidentally detected a cardiac tumor in the right atrium. On echocardiography, the tumor was revealed to be a 30-mm round mass with thin, hyperechogenic walls and heterogeneously hypoechogenic contents. The lesion was attached to the septum. On computed tomography, the tumor appeared partly calcified and showed poor contrast enhancement. On magnetic resonance imaging, the lesion appeared isointense or slightly hyperintense in T1 and T2-weighted sequences. Myxoma was strongly suspected based on these preoperative imaging findings. The tumor was successfully excised under cardiopulmonary bypass. Gross examination confirmed that the cyst was filled with blood. The cystic walls comprised thin-layered fibrous tissue lined with endocardial cells. No tumor cells were found. The diagnosis of EBC was confirmed based on histopathological examination, and the postoperative course was uneventful. PMID- 25137332 TI - [Bilateral pulmonary artery occlusion due to primary pulmonary artery sarcoma; report of a case]. AB - 60-year-old female who complained of severe dyspnea was admitted with a diagnosis of massive pulmonary embolism. An emergency operation was undertaken due to right side heart failure. Under extracorporeal circulation with beating heart, large, white and smooth surface mass which was originated from right pulmonary artery was removed. Pathology of the mass showed low differentiated sarcoma. No evidence of other primary lesion by positron emission tomography-computed tomography (PET CT) suggested primary pulmonary artery sarcoma. We scheduled total resection of the right lung, however postoperative CT showed large mass occupying from right pulmonary artery to main pulmonary trunk. Palliative chemo radiation therapy was introduced. Pulmonary artery sarcoma mimicking pulmonary thromboembolism is so malignant that the diagnosis and treatment should not be delayed. PMID- 25137334 TI - [Successful treatment using thoracic endovascular aortic repair (TEVAR) to mycotic aortic aneurysm; report of a case]. AB - We describe a case with mycotic aneurysm in a descending thoracic aorta. We applied thoracic endovascular aortic repair (TEVAR) technique to that aortic aneurysm after administering the high dose antibiotics and controlling the infection. Postoperative course was uneventful and he was in a good condition. PMID- 25137335 TI - [Surgical treatment for infective prosthetic mitral valve endocarditis with cardiogenic shock; report of a case]. AB - We report a surgical case of active infective prosthetic mitral valve endocarditis with cardiogenic shock. The causative organism was methicillin resistant coagulase negative Staphylococci (MRCNS) During medical treatment, the prosthetic valve was abruptly detouched partially from the mitral annulus, and the patient developed rapid hemodynamic deterioration. We performed emergency re do mitral valve replacement. The postoperative course was uneventful. Rapid establishment of femoro-femoral bypass was very effective for the emergency re-do valve surgery. PMID- 25137336 TI - [Bridge to recovery with ventricular assist device support for eosinophilic myocarditis]. AB - A 39-year-old man initially presented with cough, fever, and shortness of breath. His symptom got worse gradually, and he was admitted to a nearby hospital. Echocardiography revealed a dilated left ventricle and severe left ventricular dysfunction. Despite inotropic and intra-aortic balloon pumping (IABP) support, the patient developed cardiogenic shock with fever of unknown origin, followed by multi-organ failure. A left-ventricular assist device (LVAD) was implanted. Pathologic evaluation showed an extensive eosinophil-rich inflammatory infiltrate, and consistent with the diagnosis of eosinophilic myocarditis. After high-dose steroid administration, the cardiac function improved and explantation of the LVAD was successfully performed. The patient was discharged and remains well at the 24-month follow-up. PMID- 25137337 TI - [Pulmonary metastasis from breast cancer 38 years after mastectomy; report of a case]. AB - A 76-year-old woman with a history of radical mastectomy for cancer of the right breast 38 years previously developed a solitary right lung nodule which was a metastasis from breast cancer. Diagnosis of the cause of a solitary pulmonary nodule is usually difficult in a patient with a history of extrapulmonary malignancy. A solitary pulmonary metastasis from breast cancer with a disease free interval of longer than 15 years has been quite rarely reported. We describe an unusual case of a solitary pulmonary metastasis from breast cancer 38 years after the initial treatment. PMID- 25137338 TI - [An operative case of thymic cyst with thymoma;report of a case]. AB - Thymic cyst with thymoma is a rare disease. A 67-year-old woman was referred to our hospital for right chest pain and cough. Mass shadow in the right hilum was detected in the chest radiograph. Chest computed tomography( CT) revealed a cystic mass with partially thickened wall suggesting solid tumor at the anterior mediastinum. The tumor was resected by median sternotomy. Histopathological finding was a multilocular thymic cyst with thymoma of spindle cell type. PMID- 25137339 TI - [Hemopneumothorax after thoracic sympathetic nerve block; report of a case]. AB - A 72-year-old man, who had been treated pneumothorax 50 years ago, visited a physician complaining of dyspnea after thoracic sympathetic nerve block for postherpetic neuralgia. The patient was diagnosed as pneumothorax, and was consulted to our hospital. Clinical sign and the chest radiography suggested tension hemopneumothorax, and the chest drainage was immediately performed. Although bloody fluid of 1,100 ml was initially drained, no further increase was noted. The patient was discharged on the 21st hospital day. PMID- 25137341 TI - Effects of tea intake on blood pressure: a meta-analysis of randomised controlled trials. AB - The effect of tea intake on blood pressure (BP) is controversial. We performed a meta-analysis of randomised controlled trials to determine the changes in systolic and diastolic BP due to the intake of black and green tea. A systematic search was conducted in MEDLINE, EMBASE and the Cochrane Controlled Trials Register up to May 2014. The weighted mean difference was calculated for net changes in systolic and diastolic BP using fixed-effects or random-effects models. Previously defined subgroup analyses were performed to explore the influence of study characteristics. A total of twenty-five eligible studies with 1476 subjects were selected. The acute intake of tea had no effects on systolic and diastolic BP. However, after long-term tea intake, the pooled mean systolic and diastolic BP were lower by - 1.8 (95 % CI - 2.4, - 1.1) and - 1.4 (95 % CI - 2.2, - 0.6) mmHg, respectively. When stratified by type of tea, green tea significantly reduced systolic BP by 2.1 (95 % CI - 2.9, - 1.2) mmHg and decreased diastolic BP by 1.7 (95 % CI - 2.9, - 0.5) mmHg, and black tea showed a reduction in systolic BP of 1.4 (95 % CI - 2.4, - 0.4) mmHg and a decrease in diastolic BP of 1.1 (95 % CI - 1.9, - 0.2) mmHg. The subgroup analyses showed that the BP-lowering effect was apparent in subjects who consumed tea more than 12 weeks (systolic BP - 2.6 (95 % CI - 3.5, - 1.7) mmHg and diastolic BP - 2.2 (95 % CI - 3.0, - 1.3) mmHg, both P< 0.001). The present findings suggest that long-term ( >= 12 weeks) ingestion of tea could result in a significant reduction in systolic and diastolic BP. PMID- 25137342 TI - Does antibiotic use affect childhood asthma rates in China? PMID- 25137340 TI - Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron. AB - PURPOSE: Within multiple sclerosis (MS) lesions iron is present in chronically activated microglia. Thus, iron detection with MRI might provide a biomarker for chronic inflammation within lesions. Here, we examine contributions of iron and myelin to magnetic susceptibility of lesions on quantitative susceptibility mapping (QSM). METHODS: Fixed MS brain tissue was assessed with MRI including gradient echo data, which was processed to generate field (phase), R2* and QSM. Five lesions were sectioned and evaluated by immunohistochemistry for presence of myelin, iron and microglia/macrophages. Two of the lesions had an elemental analysis for iron concentration mapping, and their phospholipid content was estimated from the difference in the iron and QSM data. RESULTS: Three of the five lesions had substantial iron deposition that was associated with microglia and positive susceptibility values. For the two lesions with elemental analysis, the QSM derived phospholipid content maps were consistent with myelin labeled histology. CONCLUSION: Positive susceptibility values with respect to water indicate the presence of iron in MS lesions, although both demyelination and iron deposition contribute to QSM. PMID- 25137343 TI - Asthma prevalence among Hispanic adults in Puerto Rico and Hispanic adults of Puerto Rican descent in the United States - results from two national surveys. AB - Abstract Objective: To assess whether asthma prevalence differs between Hispanic adults living in Puerto Rico and Hispanic adults of Puerto Rican descent living in the United States. METHODS: We used 2008-2010 Behavioral Risk Factor Surveillance System data, administered in Puerto Rico for Hispanic adults living in Puerto Rico (Hispanics in Puerto Rico), and 2008-2010 National Health Interview Survey data for Hispanic adults of Puerto Rican descent living in the United States (Puerto Rican Americans). We used 95% confidence intervals (CIs) to compare asthma prevalence between corresponding subgroups; non-overlapping CIs indicate statistical significance. Chi-square test and multivariate logistic regression were used to assess the association between current asthma status and socio-demographic factors and health risk behaviors within each Puerto Rican population. RESULTS: Current asthma prevalence among Hispanics in Puerto Rico (7.0% [6.4%-7.7%]) was significantly lower than the prevalence among Puerto Rican Americans (15.6% [13.0%-18.1%]). The prevalence among almost all socio demographic and health risk subgroups of Hispanics in Puerto Rico was significantly lower than the prevalence among the corresponding subgroups of Puerto Rican Americans. Adjusting for potential confounders did not alter the results. Asthma prevalence was significantly associated with obesity among Puerto Rican Americans (adjusted prevalence ratios [aPR]=1.5 [1.1-2.0]), and among Hispanics in Puerto Rico was associated with obesity (aPR=1.6 [1.3-1.9]), smoking (aPR=1.4 [1.1-1.9]) and being female (aPR=1.9 [1.5-2.4]). CONCLUSION: Asthma was more prevalent among Puerto Rican Americans than Hispanics in Puerto Rico. Although the observed associations did not explain all variations in asthma prevalence between these two populations, they may lay the foundation for future research. PMID- 25137344 TI - Symptoms after removal of ureteral stents. AB - BACKGROUND AND PURPOSE: Urology practices frequently encounter individuals who experience various degrees of pain/discomfort after ureteral stent removal. These symptoms have been previously proved to greatly affect functionality, convalescence time, quality of life, and healthcare costs. The etiology is unclear, but the condition is often self-limiting. We counsel individuals on their risk of having post-ureteral stent removal pain based on anecdotal data. We sought to evaluate the incidence of post-ureteral stent removal pain and attempt to find the probable cause. PATIENTS AND METHODS: All individuals who had a ureteral stent placed and subsequently removed for various etiologies (between January 2012 and May 2013) were evaluated by filling a survey conducted by a member of the healthcare team 1 to 3 weeks after ureteral stent removal. Univariate and multivariate analysis were used to assess correlation between demographics, operative procedures, convalescent time, and post-ureteral stent removal symptoms. All statistical analyses were performed using SAS((r)) software, and a P value of less than 0.05 was considered to indicate statistical significance. RESULTS: Of the 104 individuals in the final cohort, 64% had symptoms after stent removal (pain, hematuria, frequency, urgency, or fever), and among those with symptoms, 60% experienced pain/discomfort. On univariate analysis, stone basketing and indwelling stent discomfort correlated positively with pain after stent removal. On the other hand, the use of anticholinergics and a longer indwelling stent duration were associated with less pain after stent removal. On multivariate analysis, correlation with procedures involving basket extraction and indwelling stent discomfort maintained significance. CONCLUSION: Our series suggests that two of three individuals who undergo ureteral stent removal experience symptoms thereafter. Individuals undergoing stone basket extraction and those who experienced stent discomfort were more likely to have pain after stent removal. Anticholinergic use and stents indwelling for a longer time were associated with less pain after stent removal. PMID- 25137345 TI - Attenuation of anti-tuberculosis therapy induced hepatotoxicity by Spirulina fusiformis, a candidate food supplement. AB - Therapy using Isoniazid (INH) and Rifampicin (RIF) leads to induction of hepatotoxicity in some individuals undergoing anti-tuberculosis treatment. In this study, we assessed the effect of Spirulina fusiformis on INH and RIF induced hepatotoxicity in rats compared with hepatoprotective drug Silymarin. Induction of hepatotoxicity was measured by changes in the liver marker enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase). The antioxidant status was also analyzed in liver tissue homogenate and plasma by measurement of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and lipid peroxidation levels. We also aimed to study the binding and interactions of the transcription factors Pregnane X Receptor (PXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of Spirulina fusiformis by in silico methods. The administration of INH and RIF resulted in significant (p < 0.05) decrease in the antioxidant levels and total protein levels. There was also a significant (p < 0.05) increase in the levels of liver marker enzymes. Spirulina fusiformis was seen to protect the parameters from significant changes upon challenge with INH and RIF in a dose-dependent manner. This was corroborated by histological examination of the liver. The results of the in silico analyses further support the wet lab results. PMID- 25137346 TI - Clinical and pathologic characteristics of intranasal abuse of combined opioid acetaminophen medications. AB - BACKGROUND: The nonmedical abuse of prescription opioids via intranasal administration is a growing problem. The objective of this study is to investigate of the typical presentation of intranasal opioid-acetaminophen abuse and outline optimal therapy. METHODS: This study was a retrospective chart review. Patients with intranasal pathology from inhalation of combined opioid acetaminophen medications (COAMs) from 3 academic otolaryngology practices in western Pennsylvania from January 2012 to October 2012 were included in the review. RESULTS: Seven adults ranging in age from 23 to 46 years were identified with nasal complaints from the intranasal inhalation of COAMs. All patients presented with nasal pain and were found to have fibrinous necrotic nasal mucosa involving the posterior nasal cavity and nasopharynx. Of the 7 patients, 6 (85.7%) presented with a septal perforation. Pathology and culture revealed fungus in 85.7% of the patients; however, no invasive fungal disease was noted in any of the specimens. Patients did not improve with either systemic or topical antifungal therapy. Polarizable material characteristic of talc used as a tablet binder was present in the histopathology of 4 of 7 (57.1%) patients. Patients who abstained from intranasal drug use along with serial debridement demonstrated the greatest improvement. CONCLUSION: Intranasal COAM abuse causes nasal pain, tissue necrosis with potential septal and palatal perforation, and noninvasive fungal colonization. Antifungal therapy was of no benefit in the current series of patients. Current therapy should focus on recognition of the etiology of patients' pathology and encourage abstinence from intranasal use of these drugs along with serial debridements. PMID- 25137350 TI - Hydrogen bonding networks tune proton-coupled redox steps during the enzymatic six-electron conversion of nitrite to ammonia. AB - Multielectron multiproton reactions play an important role in both biological systems and chemical reactions involved in energy storage and manipulation. A key strategy employed by nature in achieving such complex chemistry is the use of proton-coupled redox steps. Cytochrome c nitrite reductase (ccNiR) catalyzes the six-electron seven-proton reduction of nitrite to ammonia. While a catalytic mechanism for ccNiR has been proposed on the basis of studies combining computation and crystallography, there have been few studies directly addressing the nature of the proton-coupled events that are predicted to occur along the nitrite reduction pathway. Here we use protein film voltammetry to directly interrogate the proton-coupled steps that occur during nitrite reduction by ccNiR. We find that conversion of nitrite to ammonia by ccNiR adsorbed to graphite electrodes is defined by two distinct phases; one is proton-coupled, and the other is not. Mutation of key active site residues (H257, R103, and Y206) modulates these phases and specifically alters the properties of the detected proton-dependent step but does not inhibit the ability of ccNiR to conduct the full reduction of nitrite to ammonia. We conclude that the active site residues examined are responsible for tuning the protonation steps that occur during catalysis, likely through an extensive hydrogen bonding network, but are not necessarily required for the reaction to proceed. These results provide important insight into how enzymes can specifically tune proton- and electron transfer steps to achieve high turnover numbers in a physiological pH range. PMID- 25137351 TI - Inhibitory effects of butein on cancer metastasis and bioenergetic modulation. AB - Tumor metastasis is the major obstacle for cancer treatment. Previous studies have shown that butein exhibits antiangiogenesis property and anticancer effects in different kinds of human cancer cells. However, the effects of butein on metastasis and energy metabolism of cancer cells are mostly unknown. This study showed that butein significantly inhibited invasion of cancer cells without acting in a cytotoxic fashion. It was further demonstrated that butien dramatically suppressed cancer metastasis by an in vivo CAM-intravasation model. Additionally, butein concentration-dependently repressed the expression and activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA). The study indicated that butein may repress MMP-9 and uPA proteolytic activities and subsequently inhibit cancer metastasis via Akt/mTOR/p70S6K translational machinery. Moreover, butein may partly suppress cancer metastasis by down-regulating ATP synthesis via both oxidative and glycolytic metabolism. The results suggest that butein is a potential antimetastatic agent worthy of further development for cancer treatment. PMID- 25137352 TI - Sensitive electrochemical sensors for simultaneous determination of ascorbic acid, dopamine, and uric acid based on Au@Pd-reduced graphene oxide nanocomposites. AB - Sensitive electrochemical sensors were fabricated with reduced graphene oxide supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd RGO-modified electrodes, well-separated oxidation peaks and enhanced peak currents of AA, DA, and UA were observed owing to the superior conductivity of RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual detection, the linear responses of AA, DA, and UA were in the concentration ranges of 0.1-1000, 0.01-100, and 0.02-500 MUM with detection limits of 0.02, 0.002, and 0.005 MUM (S/N = 3), respectively. For simultaneous detection by synchronous change of the concentrations of AA, DA, and UA, the linear response ranges were 1-800, 0.1-100, and 0.1-350 MUM with detection limits of 0.28, 0.024, and 0.02 MUM (S/N = 3), respectively. The fabricated sensors were further applied to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites have promising applications in highly sensitive and selective electrochemical sensing. PMID- 25137354 TI - A three-step process to facilitate the annulation of polycyclic aromatic hydrocarbons. AB - A new efficient three-step process to annulate polycyclic aromatic hydrocarbons (PAHs) has been developed, providing access to PAHs with saturated rings that under current chemical methods would be difficult to produce in an efficient manner. This method relies on a palladium-catalyzed cross-coupling reaction of various brominated PAHs with cyclohexanone to yield alpha-arylated ketones, which are converted to regiospecific vinyl triflates and cyclized by a palladium catalyzed intramolecular arene-vinyl triflate coupling to produce PAHs with incorporated saturated rings or "tetrahydroindeno-annulated" PAHs. PMID- 25137353 TI - Perturbation of long-range water dynamics as the mechanism for the antifreeze activity of antifreeze glycoprotein. AB - Very little is known about the mechanism of antifreeze action of antifreeze glycoproteins (AFGPs) present in Antarctic teleost fish. Recent NMR and CD studies assisted with total synthesis of synthetic AFGP variants have provided insight into the structure of short AFGP glycopeptides, though the observations did not yield information on the antifreeze mechanism of action. In this study, we use Hamiltonian replica exchange (HREX) molecular dynamics simulations to probe the structure and surrounding aqueous environments of both the natural (AFGP8) and synthetic (s-AFGP4) AFGPs. AFGPs can adopt both amphiphilic and pseudoamphiphilic conformations, the preference of which is related to the proline content of the peptide. The arrangement of carbohydrates allows the hydroxyl groups on terminal galactose units to form stable water bridges which in turn influence the hydrogen-bond network, structure, and dynamics of the surrounding solvent. Interestingly, these local effects lead to the perturbation of the tetrahedral environment for water molecules in hydration layers far (10.0 12.0 A) from the AFGPs. This structure-induced alteration of long-range hydration dynamics is proposed to be the major contributor to antifreeze activity, a conclusion that is in line with terahertz spectroscopy experiments. The detailed structure-mechanism correlation provided in this study could lead to the design of better synthetic AFGP variants. PMID- 25137356 TI - A statewide survey of adult and pediatric outpatient palliative care services. AB - BACKGROUND: Outpatient palliative care services can improve patient outcomes, yet little is known about their structure and characteristics. OBJECTIVE: To describe the structure and characteristics of outpatient palliative care services associated with California hospitals. DESIGN: Electronic survey. SETTING/SUBJECTS: All 377 acute care hospitals in California. MEASUREMENTS: Outpatient palliative care services structure and operational characteristics, including staffing, clinical availability, and funding. RESULTS: Overall 96% (361/377) of hospitals responded. Of the 136 hospitals with an adult palliative care service, 18% (n=24) reported an outpatient palliative care service with a mean age of 3.7 years. Of the 42 hospitals offering pediatric palliative care services, 19% (n=8) reported an outpatient palliative care service with a mean age of 3.4 years. On average, adult outpatient palliative care services see 159 new patients per year with 722 follow-up visits. Pediatric outpatient palliative care services see 10 new patients per year with 28 follow-up visits. The average staffing of adult outpatient palliative care services is 2.1 full-time equivalent (FTE; range, 0.2-12) and for pediatric outpatient palliative care services 0.7 FTE (range, 0.1-2.0). Adult outpatient palliative care services operate a mean of 3.9 days per week compared to 1.1 days per week for pediatric outpatient palliative care services. Few services provided 24/7 coverage (25% adult, 38% pediatric). Wait times for newly referred patients were 11 days for adults and 9 days for pediatrics. Most referrals are received from oncology (adult=47%, pediatric=43%). Funding for outpatient palliative care services is largely through institutional support (adult=80%, pediatric=62%), followed by foundations (adult=10.3%, pediatric=23%), billing (adult=8.8%, pediatric=0%), and philanthropy (adult=0.9%, pediatric=15%). Compared to similar data from 2007, the prevalence of outpatient palliative care services affiliated with hospitals in California has not changed significantly. CONCLUSIONS: Few California hospitals offer outpatient palliative care services. This finding has remained consistent over time. Adult and pediatric outpatient palliative care services care primarily for patients with cancer, operate part-time with modest staffing, and are funded primarily by their institution. Making the case for value to engender more institutional support, increasing billing revenue, system initiatives, and partnering with insurers may lead to the establishment of more outpatient palliative care services. PMID- 25137357 TI - Synthesis, detailed characterization, and theoretical understanding of mononuclear chromium(III)-containing polyoxotungstates [Cr(III)(HX(V)W7O28)2]13- (X = P, As) with exceptionally large magnetic anisotropy. AB - Two monochromium(III)-containing heteropolytungstates, [Cr(III)(HP(V)W7O28)2](13 ) (1a) and [Cr(III)(HAs(V)W7O28)2](13-) (2a), were prepared via simple, one-pot reactions in aqueous, basic medium, by reaction of the composing elements, and then isolated as hydrated sodium salts, Na13[Cr(III)(HP(V)W7O28)2].47H2O (1) and Na13[Cr(III)(HAs(V)W7O28)2].52H2O (2). Polyanions 1a and 2a comprise an octahedrally coordinated Cr(III) ion, sandwiched by two {PW7} or {AsW7} units. Both compounds 1 and 2 were fully characterized in the solid state by single crystal XRD, IR spectroscopy, thermogravimetric and elemental analyses, magnetic susceptibility, and EPR measurements. Magnetic studies on 1 and 2 demonstrated that both compounds exhibit appreciable deviation from typical paramagnetic behavior, and have a ground state S = 3/2, as expected for a Cr(III) ion, but with an exceptionally large zero-field uniaxial anisotropy parameter (D). EPR measurements on powder and single-crystal samples of 1 and 2 using 9.5, 34.5, and 239.2 GHz frequencies and over 4-295 K temperature fully support the magnetization results and show that D = +2.4 cm(-1), the largest and sign assigned D-value so far reported for an octahedral Cr(III)-containing, molecular compound. Ligand field analysis of results from CASSCF and NEVPT2-correlated electronic structure calculations on Cr(OH)6(3-) model complexes allowed to unravel the crucial role of the second coordination sphere of Cr(III) for the unusually large magnetic anisotropy reflected by the experimental value of D. The newly developed theoretical modeling, combined with the synthetic procedure for producing such unusual magnetic molecules in a well-defined and essentially magnetically isolated environment, appears to be a versatile new research area. PMID- 25137358 TI - Amino acids as chiral auxiliaries in cyanuric chloride-based chiral derivatizing agents for enantioseparation by liquid chromatography. AB - This review summarizes and critically evaluates the recent research on application of amino acids and amino acid amides as chiral auxiliaries in cyanuric chloride (CC) based chiral derivatizing agents (CDRs), used in the indirect approach for enantiomeric resolution. Methods of synthesis of such CDRs, methods for synthesis of diastereomers of a variety of racemic compounds and parameters of liquid chromatographic separation, along with their prospects and their limitations in indirect enantioresolution, are discussed. Application of the said CDR(s) and the technical approach to be used that are discussed should be beneficial for control of enantiomeric purity in pharmaceutical industry, verification of enantiomeric ratio of commercial formulations and the development of methods for indirect resolution of a variety of chiral compounds. Derivatization methods are particularly required when a chromophore is to be introduced in low UV absorbing molecules, for their detection. PMID- 25137359 TI - Reconstructing Austronesian population history in Island Southeast Asia. AB - Austronesian languages are spread across half the globe, from Easter Island to Madagascar. Evidence from linguistics and archaeology indicates that the 'Austronesian expansion,' which began 4,000-5,000 years ago, likely had roots in Taiwan, but the ancestry of present-day Austronesian-speaking populations remains controversial. Here, we analyse genome-wide data from 56 populations using new methods for tracing ancestral gene flow, focusing primarily on Island Southeast Asia. We show that all sampled Austronesian groups harbour ancestry that is more closely related to aboriginal Taiwanese than to any present-day mainland population. Surprisingly, western Island Southeast Asian populations have also inherited ancestry from a source nested within the variation of present-day populations speaking Austro-Asiatic languages, which have historically been nearly exclusive to the mainland. Thus, either there was once a substantial Austro-Asiatic presence in Island Southeast Asia, or Austronesian speakers migrated to and through the mainland, admixing there before continuing to western Indonesia. PMID- 25137365 TI - Development of an organic lateral resolution test device for imaging mass spectrometry. AB - An organic lateral resolution test device has been developed to measure the performance of imaging mass spectrometry (IMS) systems. The device contains periodic gratings of polyethylene glycol (PEG) and lipid bars covering a wide range of spatial frequencies. Microfabrication technologies were employed to produce well-defined chemical interfaces, which allow lateral resolution to be assessed using the edge-spread function (ESF). In addition, the design of the device allows for the direct measurement of the modulation transfer function (MTF) to assess image quality. Scanning electron microscopy (SEM) and time-of flight secondary ion mass spectrometry (TOF-SIMS) were used to characterize the device. TOF-SIMS imaging was used to measure the chemical displacement of biomolecules in matrix-assisted laser desorption/ionization (MALDI) matrix crystals. In a proof-of-concept experiment, the platform was also used to evaluate MALDI matrix application methods, specifically aerosol spray and sublimation methods. PMID- 25137366 TI - Reconciling "stress" and "health" in physical anthropology: what can bioarchaeologists learn from the other subdisciplines? AB - The concepts of "stress" and "health" are foundational in physical anthropology as guidelines for interpreting human behavior and biocultural adaptation in the past and present. Though related, stress and health are not coterminous, and while the term "health" encompasses some aspects of "stress," health refers to a more holistic condition beyond just physiological disruption, and is of considerable significance in contributing to anthropologists' understanding of humanity's lived experiences. Bioarchaeological interpretations of human health generally are made from datasets consisting of skeletal markers of stress, markers that result from (chronic) physiological disruption (e.g., porotic hyperostosis; linear enamel hypoplasia). Non-specific indicators of stress may measure episodes of stress and indicate that infection, disease, or nutritional deficiencies were present in a population, but in assessing these markers, bioarchaeologists are not measuring "health" in the same way as are human biologists, medical anthropologists, or primatologists. Rather than continue to diverge on separate (albeit parallel) trajectories, bioarchaeologists are advised to pursue interlinkages with other subfields within physical anthropology toward bridging "stress" and "health." The papers in this special symposium set include bioarchaeologists, human biologists, molecular anthropologists, and primatologists whose research develops this link between the concepts of "stress" and "health," encouraging new avenues for bioarchaeologists to consider and reconsider health in past human populations. PMID- 25137367 TI - Effect of prolonged sitting and breaks in sitting time on endothelial function. AB - Sitting time (ST) is associated with cardiovascular disease risk factors, whereas breaking ST has been reported to be beneficial for reducing cardiovascular risk. PURPOSE: The objective of this study is to examine the effects of breaking ST on superficial femoral artery (SFA) endothelial function. HYPOTHESES: 1) Prolonged sitting would induce endothelial dysfunction and changes in shear forces, and 2) breaking ST with brief periods of activity would prevent attenuation in endothelial function. METHODS: Twelve nonobese men (24.2 +/- 4.2 yr) participated in two randomized 3-h sitting trials. In the sitting (SIT) trial, subjects were seated on a firmly cushioned chair for 3 h without moving their lower extremities. In the breaking ST trial (ACT), subjects sat similar to the SIT trial but walked on a treadmill for 5 min at 2 mph at 30 min, 1 h 30 min, and 2 h 30 min during the sitting interval. SFA flow-mediated dilation (FMD) was assessed at baseline, 1 h, 2 h, and 3 h in each trial. Statistical analyses were performed using dependent variables SFA FMD and shear rates. Significance was set at P <= 0.05. RESULTS: In the SIT trial, there was a significant decline in SFA FMD from baseline to 3 h (baseline, 4.72% +/- 3.78%; 1 h, 0.52% +/- 0.85%; 2 h, 1.66% +/- 1.11%; 3 h, 2.2% +/- 2.15; P < 0.05 by ANOVA) accompanied by a decline in mean shear rate and antegrade shear rate but no difference in shear rate (area under the curve). By two-way repeated-measures ANOVA, ACT prevented the sitting-induced decline in FMD (baseline, 4.5% +/- 2.3%; 1 h, 5.04% +/- 2.85%; 2 h, 5.28% +/- 5.05%; 3 h, 6.9% +/- 4.5%) along with no decline in shear rates. CONCLUSION: Three hours of sitting resulted in a significant impairment in shear rate and SFA FMD. When light activity breaks were introduced hourly during sitting, the decline in FMD was prevented. PMID- 25137368 TI - Eccentric hamstring strength and hamstring injury risk in Australian footballers. AB - PURPOSE: Are eccentric hamstring strength and between-limb imbalance in eccentric strength, measured during the Nordic hamstring exercise, risk factors for hamstring strain injury (HSI)? METHODS: Elite Australian footballers (n = 210) from five different teams participated. Eccentric hamstring strength during the Nordic exercise was obtained at the commencement and conclusion of preseason training and at the midpoint of the season. Injury history and demographic data were also collected. Reports on prospectively occurring HSI were completed by the team medical staff. Relative risk (RR) was determined for univariate data, and logistic regression was employed for multivariate data. RESULTS: Twenty-eight new HSI were recorded. Eccentric hamstring strength below 256 N at the start of the preseason and 279 N at the end of the preseason increased the risk of future HSI 2.7-fold (RR, 2.7; 95% confidence interval, 1.3 to 5.5; P = 0.006) and 4.3-fold (RR, 4.3; 95% confidence interval, 1.7 to 11.0; P = 0.002), respectively. Between limb imbalance in strength of greater than 10% did not increase the risk of future HSI. Univariate analysis did not reveal a significantly greater RR for future HSI in athletes who had sustained a lower limb injury of any kind within the last 12 months. Logistic regression revealed interactions between both athlete age and history of HSI with eccentric hamstring strength, whereby the likelihood of future HSI in older athletes or athletes with a history of HSI was reduced if an athlete had high levels of eccentric strength. CONCLUSION: Low levels of eccentric hamstring strength increased the risk of future HSI. Interaction effects suggest that the additional risk of future HSI associated with advancing age or previous injury was mitigated by higher levels of eccentric hamstring strength. PMID- 25137370 TI - Low-frequency severe-intensity interval training improves cardiorespiratory functions. AB - PURPOSE: The present study investigated the effects of severe-intensity interval training at a frequency of once a week on cardiorespiratory function at rest and during exercise. METHODS: Fourteen young healthy males were randomly assigned to either an interval training group or control group. Cardiorespiratory function was investigated by incremental maximal exercise test and constant work rate submaximal exercise test before and after the intervention period in all subjects. Submaximal exercise test was conducted at two work rates (80% ventilatory threshold (VT) level and 100% VT level plus 50% of the difference between VT and peak oxygen consumption (VO2)) for 8 min; the same work rates and duration were used before and after training. Left ventricular adaptations were assessed by echocardiography under supine resting conditions before and after training. In the interval training group, seven subjects performed cycle ergometer training once per week for 3 months. The training consisted of three bouts of exercises to volitional fatigue at 80% maximum work rate. RESULTS: Increased VO2max (+13%, P = 0.015), VT (+21%, P = 0.001), and left ventricular posterior wall thickness (+18%, P = 0.002) and reduced minute ventilation (-12%, P = 0.032) and blood lactate concentration (-16%, P = 0.025) during high intensity exercise were observed after the training program compared with baseline. Although not significant, VO2 and cycling economy (VO2 per work rate) during high-intensity exercise decreased slightly after training. CONCLUSION: The present results indicate that severe-intensity interval training, even when performed at a low frequency, markedly improves cardiorespiratory function as well as induces cardiac morphological adaptations involving left ventricular hypertrophy and cardiorespiratory metabolic response during submaximal exercise. The present findings may provide new insights for low-frequency, severe-intensity interval training in the field of sports science. PMID- 25137369 TI - Accelerometer adherence and performance in a cohort study of US Hispanic adults. AB - PURPOSE: This study described participant adherence to wearing the accelerometer and accelerometer performance in a cohort study of adults. METHODS: From 2008 to 2011, 16,415 US Hispanic/Latino adults age 18-74 yr enrolled in the Hispanic Community Health Study/Study of Latinos. Immediately after the baseline visit, participants wore an Actical accelerometer for 1 wk. This study explored correlates of accelerometer participation and adherence, defined as wearing it for at least three of a possible six days for >=10 h.d. Accelerometer performance was assessed by exploring the number of different values of accelerometer counts per minute for each participant. RESULTS: Overall, 92.3% (n = 15,153) had at least 1 d with accelerometer data and 77.7% (n = 12,750) were adherent. Both accelerometer participation and adherence were higher among participants who were married or partnered, reported a higher household income, were first-generation immigrants, or reported lower sitting time. Participation was also higher among those with no stair limitations. Adherence was higher among participants who were male, older, employed or retired, not US born, preferred Spanish over English, reported higher work activity or lower recreational activity, and with a lower body mass index. Among the sample that met the adherence definition, the maximum recorded count per minute was 12,000, and there were a total of 5846 different counts per minute. On average, participants had 112.5 different counts per minute over 6 d (median, 106; interquartile range, 91-122). The number of different counts per minute was higher among men, younger ages, normal weight, and those with higher accelerometer-assessed physical activity. CONCLUSION: Several correlates differed between accelerometer participation and adherence. These characteristics could be targeted in future studies to improve accelerometer wear. The performance of the accelerometer provided insight into creating a more accurate nonwear algorithm. PMID- 25137372 TI - Long-term fertilization modifies the structures of soil fulvic acids and their binding capability with Al. AB - The binding characteristics of organic ligands and minerals in fulvic acids (FAs) with Al are essential for understanding soil C sequestration, remain poorly understood. In this study, Fourier transform infrared (FTIR) spectroscopy combined with two-dimensional correlation spectroscopy (2DCOS) analysis was applied for the first time to explore the binding of Al with organic ligands and minerals in soil FAs. For these analyses, two contrasting treatments were selected from a long-term (i.e., 22-year) fertilization experiment: chemical (NPK) fertilization and swine manure (SM) fertilization. The results showed that the long-term application of organic and inorganic fertilizers to soils had little effect on the compositions of the fluorescent substances and organic ligands in the soil FAs. However, long-term SM fertilization increased the weathered Al and Si concentrations in the soil FAs compared with long-term chemical fertilization. Furthermore, organic ligands in the soil FAs were mainly bound with Al in the NPK treatment, whereas both organic ligands and minerals (Al O-Si, Si-O) were bound with Al under the M fertilization conditions. Both transmission electron microscopy (TEM) images and X-ray diffraction spectra demonstrated that amorphous and short-range-ordered nanominerals were abundant in the soil FAs from the SM plot in contrast to the soil FAs from the NPK plot. This result illustrates the role nanominerals play in the preservation of soil FAs by during long-term organic fertilization. In summary, the combination of FTIR and 2D correlation spectroscopy is a promising approach for the characterization of the binding capability between soil FAs and Al, and a better understanding FA-Al binding capability will greatly contribute to global C cycling. PMID- 25137373 TI - Functional networks of nucleocytoplasmic transport-related genes differentiate ischemic and dilated cardiomyopathies. A new therapeutic opportunity. AB - Heart failure provokes alterations in the expression of nucleocytoplasmic transport-related genes. To elucidate the nucleocytoplasmic transport-linked functional network underlying the two major causes of heart failure, ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined global transcriptome profiles of left ventricular myocardium tissue samples from 31 patients (ICM, n = 10; DCM, n = 13) undergoing heart transplantation and control donors (CNT, n = 8) using RNA-Sequencing and GeneMANIA. Comparative profiling of ICM versus control and DCM versus control showed 1081 and 2440 differentially expressed genes, respectively (>1.29-fold; P<0.05). GeneMANIA revealed differentially regulated functional networks specific to ICM and DCM. In comparison with CNT, differential expression was seen in 9 and 12 nucleocytoplasmic transport-related genes in ICM and DCM groups, respectively. DDX3X, KPNA2, and PTK2B were related to ICM, while SMURF2, NUP153, IPO5, RANBP3, NOXA1, and RHOJ were involved in DCM pathogenesis. Furthermore, the two pathologies shared 6 altered genes: XPO1, ARL4, NFKB2, FHL3, RANBP2, and RHOU showing an identical trend in expression in both ICM and DCM. Notably, the core of the derived functional networks composed of nucleocytoplasmic transport related genes (XPO1, RANBP2, NUP153, IPO5, KPNA2, and RANBP3) branched into several pathways with downregulated genes. Moreover, we identified genes whose expression levels correlated with left ventricular mass index and left ventricular function parameters in HF patients. Collectively, our study provides a clear distinction between the two pathologies at the transcriptome level and opens up new possibilities to search for appropriate therapeutic targets for ICM and DCM. PMID- 25137375 TI - Discovery of covalent inhibitors of glyceraldehyde-3-phosphate dehydrogenase, a target for the treatment of malaria. AB - We developed a new class of covalent inhibitors of Plasmodium falciparum glyceraldehyde-3-phosphate dehydrogenase, a validated target for the treatment of malaria, by screening a small library of 3-bromo-isoxazoline derivatives that inactivate the enzyme through a covalent, selective bond to the catalytic cysteine, as demonstrated by mass spectrometry. Substituents on the isoxazolinic ring modulated the potency up to 20-fold, predominantly due to an electrostatic effect, as assessed by computational analysis. PMID- 25137374 TI - The ginsenoside 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol induces autophagy and apoptosis in human melanoma via AMPK/JNK phosphorylation. AB - Studies have shown that a major metabolite of the red ginseng ginsenoside Rb1, called 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (GPD), exhibits anticancer properties. However, the chemotherapeutic effects and molecular mechanisms behind GPD action in human melanoma have not been previously investigated. Here we report the anticancer activity of GPD and its mechanism of action in melanoma cells. GPD, but not its parent compound Rb1, inhibited melanoma cell proliferation in a dose-dependent manner. Further investigation revealed that GPD treatment achieved this inhibition through the induction of autophagy and apoptosis, while Rb1 failed to show significant effect at the same concentrations. The inhibitory effect of GPD appears to be mediated through the induction of AMPK and the subsequent attenuation of mTOR phosphorylation. In addition, GPD activated c-Jun by inducing JNK phosphorylation. Our findings suggest that GPD suppresses melanoma growth by inducing autophagic cell death and apoptosis via AMPK/JNK pathway activation. GPD therefore has the potential to be developed as a chemotherapeutic agent for the treatment of human melanoma. PMID- 25137376 TI - Susceptibility-weighted imaging in heat stroke. AB - OBJECTIVE: To assess the role of susceptibility-weighted imaging in the detection of intracranial hemorrhage after heat stroke and in the prognosis. MATERIALS AND METHODS: The study group consisted of eight patients after heat stroke, with a score of 3 to 9 in Glasgow Coma Scale. The MR studies were performed with a 1.5 T scanner. Susceptibility-weighted imaging data were collected within 2-5 days after heat stroke. The study was approved by ethics committee, and written informed consents were obtained from family members of the patients. RESULTS: Punctate hemorrhages were detected in brain stem, corona radiata and frontal lobe by susceptibility-weighted imaging for three patients. Among the three cases, two patients came to death in the 5th day and the 25th day after heat stroke respectively. Another patient became a persistent vegetative state and died about 3 months later. Five patients with no hemorrhage detected gradually recovered and cerebellar dysfunction remained to various degrees. CONCLUSIONS: Heat stroke is a life-threatening condition characterized by hyperthermia and accompanied by various complications such as disseminated intravascular coagulation. Susceptibility-weighted imaging is a very useful tool for detection of intracranial hemorrhage and may probably evaluate the prognosis after heat stroke. PMID- 25137377 TI - Central venous-to-arterial CO2-gap may increase in severe isovolemic anemia. AB - Despite blood transfusions are administered to restore adequate tissue oxygenation, transfusion guidelines consider only hemoglobin as trigger value, which gives little information about the balance between oxygen delivery and consumption. Central venous oxygen saturation is an alternative, however its changes reflect systemic metabolism and fail to detect regional hypoxia. A complementary parameter to ScvO2 may be central venous-to-arterial carbon dioxide difference (CO2-gap). Our aim was to investigate the change of alternative transfusion trigger values in experimental isovolemic anemia. After splenectomy, anesthetized Vietnamese mini pigs (n = 13, weight range: 18-30 kg) underwent controlled bleeding in five stages (T1-T5). During each stage approximately 10% of the estimated starting total blood volume was removed and immediately replaced with an equal volume of colloid. Hemodynamic measurements and blood gas analysis were then performed. Each stage of bleeding resulted in a significant fall in hemoglobin, the O2-extraction increased significantly from T3 and ScvO2 showed a similar pattern and dropped below the physiological threshold of 70% at T4. By T4 CO2-gap increased significantly and well correlated with VO2/DO2 and ScvO2. To our knowledge, this is the first study to show that anemia caused altered oxygen extraction may have an effect on CO2-gap. PMID- 25137378 TI - Can POCIS be used in Water Framework Directive (2000/60/EC) monitoring networks? A study focusing on pesticides in a French agricultural watershed. AB - In this study, the main current limitations in the application of the Polar Organic Chemical Integrative Sampler (POCIS) in regulatory monitoring programmes were evaluated. POCIS were exposed from March to December by successive periods of 14 days in the River Trec (Lot et Garonne, France) and analysed for 34 pesticides. The study of the uncertainty related to the POCIS data was performed and we concluded that it might be up to 138%, which is higher than European Union requirements but this issue was adequately counterbalanced by the gain of temporal representativeness. Comparison with data from the official monitoring programme from the French Water Agency showed that the POCIS is already suitable for both operational and investigative monitoring. The sampled fraction issue, and then compliance with Environmental Quality Standards, was also addressed. It was confirmed that POCIS samples only the dissolved fraction of dimethenamid and showed that for compounds like atrazine, desethylatrazine and metolachlor, the POCIS concentration is equivalent to the whole water concentration. For dimethenamid, which exhibited a tendency to adsorb on suspended matter, a method was suggested to assess the raw water concentration from the POCIS measure. Finally, an innovative procedure for using passive sampler data for compliance checks in the framework of surveillance monitoring is proposed. PMID- 25137379 TI - The impact of organochlorines and metals on wild fish living in a tropical hydroelectric reservoir: bioaccumulation and histopathological biomarkers. AB - This study evaluates the contaminants in water and their bioaccumulation in the gills and liver of two ecologically distinct fish species, Astyanax fasciatus and Pimelodus maculatus, living in the reservoir of the Furnas hydroelectric power station located in Minas Gerais in the southeastern Brazil. The histological alterations in these organs are also examined. Water and fish were collected in June and December from five sites (site 1: FU10, site 2: FU20, site 3: FU30, site 4: FU40 and site 5: FU50) in the reservoir, and agrochemicals and metals selected based on their use in the field crops surrounding the reservoir were analyzed in the water and in the fish gills and livers. The concentrations of the organochlorines aldrin/dieldrin, endosulfan and heptachlor/heptachlor epoxide as well as the metals copper, chromium, iron and zinc in the gills and livers of both fish species were higher in June than in December; the liver accumulated higher concentrations of contaminants than the gills. The organochlorine metolachlor was detected only in the liver. The histological pattern of changes was similar in both species with regard to contaminant accumulation in the gills and liver. Fish from FU10, the least contaminated site, exhibited normal gill structure and moderate to heavy liver damage. Fish collected at FU20 to FU50, which were contaminated with organochlorines and metals, showed slight to moderate gill damage in June and irreparable liver damage in the livers in June and December. The histological changes in the gills and liver were suitable to distinguishing contaminated field sites and are therefore useful biomarkers for environmental contamination representing a biological end-point of exposure. PMID- 25137380 TI - A multi-level biological approach to evaluate impacts of a major municipal effluent in wild St. Lawrence River yellow perch (Perca flavescens). AB - The development of integrated ecotoxicological approaches is of great interest in the investigation of global concerns such as impacts of municipal wastewater effluents on aquatic ecosystems. The objective of this study was to investigate the effects of a major wastewater municipal effluent on fish using a multi-level biological approach, from gene transcription and enzyme activities to histological changes. Yellow perch (Perca flavescens) were selected based on their wide distribution, their commercial and recreational importance, and the availability of a customized microarray. Yellow perch were sampled upstream of a major municipal wastewater treatment plant (WWTP) and 4 km and 10 km downstream from its point of discharge in the St. Lawrence River (Quebec, Canada). Concentrations of perfluoroalkyl substances (PFASs), polybrominated diphenyl ethers (PBDEs) and metals/trace elements in whole body homogenates were comparable to those from other industrialized regions of the world. Genomic results indicated that the transcription level of 177 genes was significantly different (p<0.024) between exposed and non-exposed fish. Among these genes, 38 were found to be differentially transcribed at both downstream sites. Impacted genes were associated with biological processes and molecular functions such as immunity, detoxification, lipid metabolism/energy homeostasis (e.g., peroxisome proliferation), and retinol metabolism suggesting impact of WWTP on these systems. Moreover, antioxidant enzyme activities were more elevated in perch collected at the 4 km site. Biomarkers of lipid metabolism, biosynthetic activity, and aerobic capacities were significantly lower (p<0.05) in fish residing near the outfall of the effluent. Histological examination of the liver indicated no differences between sites. Correlations between PFAS, PBDE, and metal/trace element tissue concentrations and markers of peroxisomal proliferation, oxidative stress, and retinoid metabolism were found at the gene and cellular levels. Present results suggest that relating transcriptomic analyses to phenotypic responses is important to better understand impacts of environmental contamination on wild fish populations. PMID- 25137381 TI - Antimony in the soil-water-plant system at the Su Suergiu abandoned mine (Sardinia, Italy): strategies to mitigate contamination. AB - This study was aimed to implement the understanding of the Sb behavior in near surface environments, as a contribution to address appropriate mitigation actions at contaminated sites. For this purpose, geochemical data of soil (8 sites), water (29 sites), and plant (12 sites) samples were collected. The study area is located at Su Suergiu and surroundings in Sardinia (Italy), an abandoned mine area heavily contaminated with Sb, with relevant impact on water bodies that supply water for agriculture and domestic uses. Antimony in the soil horizons ranged from 19 to 4400 mg kg(-1), with highest concentrations in soils located close to the mining-related wastes, and concentrations in the topsoil much higher than in the bedrock. The Sb readily available fraction was about 2% of the total Sb in the soil. Antimony in the pore water ranged from 23 to 1700 MUg L(-1), with highest values in the Sb-rich soils. The waters showed neutral to slightly alkaline pH, redox potential values indicating oxidizing conditions, electrical conductivity in the range of 0.2 to 3.7 mS cm(-1), and dissolved organic carbon <=2 mg L(-1). The waters collected upstream of the mine have Ca-bicarbonate dominant composition, and median concentration of Sb(tot) of 1.7 MUg L(-1) (that is total antimony determined in waters filtered through 0.45 MUm), a value relatively high as compared with the background value (<=0.5 MUg L(-1) Sb) estimated for Sardinian waters, but below the limits established by the European Union and the World Health Organization for drinking water (5 MUg L(-1) Sb and 20 MUg L(-1) Sb, respectively). The waters flowing in the mine area are characterized by Ca-sulfate dominant composition, and median concentrations of 7000 MUg L(-1) Sb(tot). Extreme concentrations, up to 30,000 MUg L(-1) Sb(tot), were observed in waters flowing out of the slag materials derived from the processing of Sb-ore. The Sb(III) was in the range of 0.8 to 760 MUg L(-1) and represented up to 6% of Sb(tot). In the waters collected downstream of the mine, median Sb(tot) concentrations decreased as distance from the mine area increases: 1300 MUg L(-1) Sb(tot) in the stream Rio Ciurixeda at 3 km distance, and 25 MUg L(-1) Sb(tot) in the main River Flumendosa 15 km further downstream. Attenuation of Sb contamination was mainly due to dilution. Results of modeling, carried out by both EQ3 and Visual MINTEQ computer programs, suggest that sorption of dissolved Sb onto solid phases, and/or precipitation of Sb-bearing minerals, likely give a minor contribution to attenuation of Sb contamination. The slightly alkaline pH and oxidizing conditions might favor the persistence of inorganic Sb(V)-bearing species at long distance in the studied waters. Concentrations of Sb in the plants Pistacia lentiscus and Asparagus ranged from 0.1 to 22 mg kg( 1), with maximum values in plants growing very close to the mining-related wastes. The P. lentiscus grows well on the soils highly contaminated with Sb at Su Suergiu and might be used for revegetation of the Sb-rich heaps, thus contributing to reduce the dispersion of contaminated materials. Major effects of contamination were observed on the water bodies located downstream of the Su Suergiu abandoned mine. The maximum load (16.6 kg Sb per day) to the Flumendosa, the main aquatic recipient, was observed after heavy rain events. Therefore, priorities of mitigation actions should be focused on minimizing the contact of rain and runoff waters on the heaps of mining wastes. PMID- 25137382 TI - Impact of fresh organic matter incorporation on PAH fate in a contaminated industrial soil. AB - The impacts of fresh organic matter (OM) incorporation in an industrial PAH contaminated soil on its structure and contaminant concentrations (available and total) were monitored. A control soil and a soil amended with the equivalent of 10 years maize residue input were incubated in laboratory-controlled conditions over 15 months. The structure of the amended soil showed an aggregation process trend which is attributable to (i) the enhanced microbial activity resulting from fresh OM input itself and (ii) the fresh OM and its degradation products. Initially the added organic matter was evenly distributed among all granulodensimetric fractions, and then rapidly degraded in the sand fraction, while stabilizing and accumulating in the silts. PAH degradation remained slight, despite the enhanced microbial biomass activity, which was similar to kinetics of the turnover rate of OM in an uncontaminated soil. The silts stabilized the anthropogenic OM and associated PAH. The addition of fresh OM tended to contribute to this stabilization process. Thus, in a context of plant growth on this soil two opposing processes might occur: rhizodegradation of the available contaminant and enhanced stabilization of the less available fraction due to carbon input. PMID- 25137383 TI - Comparative study on PCDD/F pollution in soil from the Antarctic, Arctic and Tibetan Plateau. AB - The concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in 35 soil samples collected from Fildes Peninsula in the Antarctic, Ny Alesund in the Arctic, and Zhangmu-Nyalam in the Tibetan Plateau were reported in this study. A comparison of the total concentration and TEQ of PCDD/Fs at the Three Poles was conducted. Both the total concentration and TEQ of PCDD/Fs demonstrates a decreasing trend in the order of Zhangmu-Nyalam (mean: 26.22 pg/g, 0.37 pg I-TEQ/g)>Ny-Alesund (mean: 9.97 pg/g, 0.33 pg I-TEQ/g)>Fildes Peninsula (mean: 2.18 pg/g, 0.015 pg I-TEQ/g) (p<0.05). In all samples, the congener and homologue profiles dominated with higher (seven and eight) chlorinated PCDD/Fs (more than 85% of the total mass percentage of PCDD/Fs) at the Three Poles. Finally, a FLEXPART backward simulation was used to preliminarily identify the potential local and regional anthropogenic sources of PCDD/Fs. The results imply that the air masses passing over surrounding regions with significant PCDD/F emissions might contribute to the occurrence of PCDD/Fs in both the Arctic and Tibetan Plateau. PMID- 25137384 TI - Advanced hybrid supercapacitor based on a mesoporous niobium pentoxide/carbon as high-performance anode. AB - Recently, hybrid supercapacitors (HSCs), which combine the use of battery and supercapacitor, have been extensively studied in order to satisfy increasing demands for large energy density and high power capability in energy-storage devices. For this purpose, the requirement for anode materials that provide enhanced charge storage sites (high capacity) and accommodate fast charge transport (high rate capability) has increased. Herein, therefore, a preparation of nanocomposite as anode material is presented and an advanced HSC using it is thoroughly analyzed. The HSC comprises a mesoporous Nb2O5/carbon (m-Nb2O5-C) nanocomposite anode synthesized by a simple one-pot method using a block copolymer assisted self-assembly and commercial activated carbon (MSP-20) cathode under organic electrolyte. The m-Nb2O5-C anode provides high specific capacity with outstanding rate performance and cyclability, mainly stemming from its enhanced pseudocapacitive behavior through introduction of a carbon-coated mesostructure within a voltage range from 3.0 to 1.1 V (vs Li/Li(+)). The HSC using the m-Nb2O5-C anode and MSP-20 cathode exhibits excellent energy and power densities (74 W h kg(-1) and 18,510 W kg(-1)), with advanced cycle life (capacity retention: ~90% at 1000 mA g(-1) after 1000 cycles) within potential range from 1.0 to 3.5 V. In particular, we note that the highest power density (18,510 W kg( 1)) of HSC is achieved at 15 W h kg(-1), which is the highest level among similar HSC systems previously reported. With further study, the HSCs developed in this work could be a next-generation energy-storage device, bridging the performance gap between conventional batteries and supercapacitors. PMID- 25137385 TI - DNA nanoparticles with core-shell morphology. AB - Mannobiose-modified polyethylenimines (PEI) are used in gene therapy to generate nanoparticles of DNA that can be targeted to the antigen-presenting cells of the immune system. We report that the sugar modification alters the DNA organization within the nanoparticles from homogenous to shell-like packing. The depth dependent packing of DNA within the nanoparticles was probed using AFM nano indentation. Unmodified PEI-DNA nanoparticles display linear elastic properties and depth-independent mechanics, characteristic of homogenous materials. Mannobiose-modified nanoparticles, however, showed distinct force regimes that were dependent on indentation depth, with 'buckling'-like response that is reproducible and not due to particle failure. By comparison with theoretical studies of spherical shell mechanics, the structure of mannobiosylated particles was deduced to be a thin shell with wall thickness in the order of few nanometers, and a fluid-filled core. The shell-core structure is also consistent with observations of nanoparticle denting in altered solution conditions, with measurements of nanoparticle water content from AFM images, and with images of DNA distribution in Transmission Electron Microscopy. PMID- 25137387 TI - A reliable and efficient protocol for human pluripotent stem cell differentiation into the definitive endoderm based on dispersed single cells. AB - Differentiation of pluripotent cells into endoderm-related cell types initially requires in vitro gastrulation into the definitive endoderm (DE). Most differentiation protocols are initiated from colonies of pluripotent cells complicating their adaption due to insufficiently defined starting conditions. The protocol described here was initiated from a defined cell number of dispersed single cells and tested on three different human embryonic stem cell lines and one human induced pluripotent stem cell line. Combined activation of ActivinA/Nodal signaling and GSK3 inhibition for the first 24 h, followed by ActivinA/Nodal signaling efficiently induced the DE state. Activation of ActivinA/Nodal signaling alone was not effective. Efficient GSK3 inhibition allowed the reduction of the ActivinA concentration during the entire protocol. A feeder-independent cultivation of pluripotent cells was preferred to achieve the high efficiency and robustness since feeder cells hindered the differentiation process. Additionally, inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway was not required, nonetheless yielding high cell numbers efficiently committed toward the DE. Finally, the endoderm generated could be differentiated further into PDX1-positive pan-pancreatic cells and NGN3-positive endocrine progenitors. Thus, this efficient and robust DE differentiation protocol is a step forward toward better reproducibility due to the well-defined conditions based on dispersed single cells from feeder-free-cultivated human pluripotent cells. PMID- 25137386 TI - Associations between stroke mortality and weekend working by stroke specialist physicians and registered nurses: prospective multicentre cohort study. AB - BACKGROUND: Observational studies have reported higher mortality for patients admitted on weekends. It is not known whether this "weekend effect" is modified by clinical staffing levels on weekends. We aimed to test the hypotheses that rounds by stroke specialist physicians 7 d per week and the ratio of registered nurses to beds on weekends are associated with mortality after stroke. METHODS AND FINDINGS: We conducted a prospective cohort study of 103 stroke units (SUs) in England. Data of 56,666 patients with stroke admitted between 1 June 2011 and 1 December 2012 were extracted from a national register of stroke care in England. SU characteristics and staffing levels were derived from cross-sectional survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) of 30-d post-admission mortality, adjusting for case mix, organisational, staffing, and care quality variables. After adjusting for confounders, there was no significant difference in mortality risk for patients admitted to a stroke service with stroke specialist physician rounds fewer than 7 d per week (adjusted HR [aHR] 1.04, 95% CI 0.91-1.18) compared to patients admitted to a service with rounds 7 d per week. There was a dose-response relationship between weekend nurse/bed ratios and mortality risk, with the highest risk of death observed in stroke services with the lowest nurse/bed ratios. In multivariable analysis, patients admitted on a weekend to a SU with 1.5 nurses/ten beds had an estimated adjusted 30-d mortality risk of 15.2% (aHR 1.18, 95% CI 1.07-1.29) compared to 11.2% for patients admitted to a unit with 3.0 nurses/ten beds (aHR 0.85, 95% CI 0.77-0.93), equivalent to one excess death per 25 admissions. The main limitation is the risk of confounding from unmeasured characteristics of stroke services. CONCLUSIONS: Mortality outcomes after stroke are associated with the intensity of weekend staffing by registered nurses but not 7-d/wk ward rounds by stroke specialist physicians. The findings have implications for quality improvement and resource allocation in stroke care. Please see later in the article for the Editors' Summary. PMID- 25137389 TI - Modulation of gephyrin-glycine receptor affinity by multivalency. AB - Gephyrin is a major determinant for the accumulation and anchoring of glycine receptors (GlyRs) and the majority of gamma-aminobutyric acid type A receptors (GABAARs) at postsynaptic sites. Here we explored the interaction of gephyrin with a dimeric form of a GlyR beta-subunit receptor-derived peptide. A 2 A crystal structure of the C-terminal domain of gephyrin (GephE) in complex with a 15-residue peptide derived from the GlyR beta-subunit defined the core binding site, which we targeted with the dimeric peptide. Biophysical analyses via differential scanning calorimetry (DSC), thermofluor, and isothermal titration calorimetry (ITC) demonstrated that this dimeric ligand is capable of binding simultaneously to two receptor binding sites and that this multivalency results in a 25-fold enhanced affinity. Our study therefore suggests that the oligomeric state of gephyrin and the number of gephyrin-binding subunits in the pentameric GABAARs and GlyRs together control postsynaptic receptor clustering. PMID- 25137390 TI - Crystal structure of the mouse interleukin-3 beta-receptor: insights into interleukin-3 binding and receptor activation. AB - Interleukin-3 (IL-3) is a cytokine secreted by mast cells and activated T-cells known to be an important regulator of differentiation, survival, proliferation and activation of a range of haemopoietic lineages. The effects of IL-3 on target cells are mediated by a transmembrane receptor system composed of a cytokine specific alpha-subunit and a beta-subunit, the principal signalling entity. In the mouse, two beta-subunits have co-evolved: a common beta-subunit (betac) shared between IL-3 and the related cytokines IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF); and an IL-3-specific beta-subunit (betaIL-3). betaIL-3 differs from betac in its specificity for IL-3 and its capacity to bind IL-3 directly in the absence of an alpha-subunit, and, in the absence of structural information, the basis for these properties has remained enigmatic. In the present study, we have solved the crystal structure of the betaIL-3 ectodomain at 3.45 A (1 A=0.1 nm) resolution. This structure provides the first evidence that betaIL-3 adopts an arch-shaped intertwined homodimer with similar topology to the paralogous betac structure. In contrast with apo-betac, however, the ligand-binding interface of betaIL-3 appears to pre-exist in a conformation receptive to IL-3 engagement. Molecular modelling of the IL-3-betaIL-3 interface, in conjunction with previous mutational studies, suggests that divergent evolution of both betaIL-3 and IL-3 underlies their unique capacity for direct interaction and specificity. PMID- 25137391 TI - Composite-walled magnetic microcapsules at the water-toluene interface by ligand polymerization. AB - The liquid-liquid interface has been exploited as a platform for devising gold and iron oxide nanoparticle (NP)-decorated composite microcapsules (MCs) by cross linking between -OH groups of poly(ethylene glycol) (PEG) attached to the iron oxide (Fe3O4) nanoparticle surface and starch attached to the gold (Au) nanoparticle surface in the presence of terephthaloyl chloride as a cross-linker. These nanoparticle-decorated capsules form a shell of both types of nanoparticles with water as the minor phase and toluene as the major phase. The morphology of these capsules has been characterized by optical, transmission, and scanning electron microscopy images, and the polymerization reaction has been established by UV-vis and FTIR spectroscopic studies. The magnetic behavior of the capsules has been illustrated by using an external magnetic field to tailor the magnetic control of the capsules. The encapsulated phase was impregnated with dye molecules of three different sizes, viz., fluorescein isothiocyanate and its dextran conjugates, to investigate the permeability of the capsule wall by fluorescence spectroscopy. Interestingly, the microcapsules exhibit size selective permeability across the capsule wall that points to their plausible applications in controlled encapsulation and release. PMID- 25137392 TI - Estimating risks and relative risks in case-base studies under the assumptions of gene-environment independence and Hardy-Weinberg equilibrium. AB - Many diseases result from the interactions between genes and the environment. An efficient method has been proposed for a case-control study to estimate the genetic and environmental main effects and their interactions, which exploits the assumptions of gene-environment independence and Hardy-Weinberg equilibrium. To estimate the absolute and relative risks, one needs to resort to an alternative design: the case-base study. In this paper, the authors show how to analyze a case-base study under the above dual assumptions. This approach is based on a conditional logistic regression of case-counterfactual controls matched data. It can be easily fitted with readily available statistical packages. When the dual assumptions are met, the method is approximately unbiased and has adequate coverage probabilities for confidence intervals. It also results in smaller variances and shorter confidence intervals as compared with a previous method for a case-base study which imposes neither assumption. PMID- 25137393 TI - Dynamic analysis and pattern visualization of forest fires. AB - This paper analyses forest fires in the perspective of dynamical systems. Forest fires exhibit complex correlations in size, space and time, revealing features often present in complex systems, such as the absence of a characteristic length scale, or the emergence of long range correlations and persistent memory. This study addresses a public domain forest fires catalogue, containing information of events for Portugal, during the period from 1980 up to 2012. The data is analysed in an annual basis, modelling the occurrences as sequences of Dirac impulses with amplitude proportional to the burnt area. First, we consider mutual information to correlate annual patterns. We use visualization trees, generated by hierarchical clustering algorithms, in order to compare and to extract relationships among the data. Second, we adopt the Multidimensional Scaling (MDS) visualization tool. MDS generates maps where each object corresponds to a point. Objects that are perceived to be similar to each other are placed on the map forming clusters. The results are analysed in order to extract relationships among the data and to identify forest fire patterns. PMID- 25137395 TI - Transformation of oxcarbazepine and human metabolites of carbamazepine and oxcarbazepine in wastewater treatment and sand filters. AB - Carbamazepine (CBZ) and oxcarbazepine (OXC) are widely used anticonvulsants that are extensively metabolized in the human body. The pharmaceuticals and their human metabolites are present in influents and effluents of wastewater treatment plants (WWTPs), in rivers and streams, and in drinking water. In this study, the biodegradation of OXC and its main human metabolite, 10-hydroxy-CBZ (10OHCBZ), and the main human metabolite of CBZ, 10,11-dihydro-10,11-dihydroxy-CBZ (DiOHCBZ), was investigated in contact with activated sludge from a wastewater treatment plant (WWTP) and sand filter material from a waterworks. The transformation of DiOHCBZ, 10OHCBZ, and OXC led to the formation of the following main TPs: 1-(2-benzoic acid)-(1H,3H)-quinazoline-2,4-dione (BaQD), 1-(2-benzoic acid)-(1H,3H)-quinazoline-2-one (BaQM), 9-aldehyde-acridine, 9-carboxylic acid acridine (9-CA-ADIN), hydroxyl 9-CA-ADIN, acridone (ADON), 11-keto-OXC, and 2,2' (carbamoylazanediyl)dibenzoic acid. TP formation could be explained by three proposed transformation pathways, including reactions such as oxidation, alpha ketol rearrangement, or benzylic acid rearrangement. The results highlight the fact that the TP abundances strongly depend on the concentrations spiked in the lab-scale experiments. BaQD, 9-CA-ADIN, and ADON were detected in WWTP effluents, rivers, and streams. 9-CA-ADIN was found at maximum concentrations in WWTP effluent and rivers up to 920 +/- 50 ng L(-1) and 304 +/- 26 ng L(-1), respectively. Even in drinking water, BaQD and 9-CA-ADIN were present at concentrations of 26 +/- 2 ng L(-1) and 189 +/- 3 ng L(-1), respectively. PMID- 25137394 TI - KRAS genotypic changes of circulating tumor cells during treatment of patients with metastatic colorectal cancer. AB - INTRODUCTION: Circulating tumor cells (CTCs) could represent a non-invasive source of cancer cells used for longitudinal monitoring of the tumoral mutation status throughout the course of the disease. The aims of the present study were to investigate the detection of KRAS mutations in CTCs from patients with metastatic colorectal cancer (mCRC) and to compare their mutation status during treatment or disease progression with that of the corresponding primary tumors. MATERIALS AND METHODS: Identification of the seven most common KRAS mutations on codons 12 and 13 was performed by Peptide Nucleic Acid (PNA)-based qPCR method. The sensitivity of the assay was determined after isolation of KRAS mutant cancer cells spiked into healthy donors' blood, using the CellSearch Epithelial Cell kit. Consistent detection of KRAS mutations was achieved in samples containing at least 10 tumor cells/7.5 ml of blood. RESULTS: The clinical utility of the assay was assessed in 48 blood samples drawn from 31 patients with mCRC. All patients had PIK3CA and BRAF wild type primary tumors and 14 KRAS mutant tumors. CTCs were detected in 65% of specimens obtained from 74% of patients. KRAS mutation analysis in CTC-enriched specimens showed that 45% and 16.7% of patients with mutant and wild type primary tumors, respectively, had detectable mutations in their CTCs. Assessing KRAS mutations in serial blood samples revealed that individual patient's CTCs exhibited different mutational status of KRAS during treatment. CONCLUSIONS: The current findings support the rationale for using the CTCs as a dynamic source of tumor cells which, by re-evaluating their KRAS mutation status, could predict, perhaps more accurately, the response of mCRC patients to targeted therapy. PMID- 25137397 TI - Considerations for assessment of reproductive and developmental toxicity of oligonucleotide-based therapeutics. AB - This white paper summarizes the current consensus of the Reproductive Subcommittee of the Oligonucleotide Safety Working Group on strategies to assess potential reproductive and/or developmental toxicities of therapeutic oligonucleotides (ONs). The unique product characteristics of ONs require considerations when planning developmental and reproductive toxicology studies, including (a) chemical characteristics, (b) assessment of intended and unintended mechanism of action, and (c) the optimal exposure, including dosing regimen. Because experience across the various classes of ONs as defined by their chemical backbone is relatively limited, best practices cannot be defined. Rather, points to consider are provided to help in the design of science-based reproductive safety evaluation programs based upon product attributes. PMID- 25137398 TI - CO2 deserts: implications of existing CO2 supply limitations for carbon management. AB - Efforts to mitigate the impacts of climate change will require deep reductions in anthropogenic CO2 emissions on the scale of gigatonnes per year. CO2 capture and utilization and/or storage technologies are a class of approaches that can substantially reduce CO2 emissions. Even though examples of this approach, such as CO2-enhanced oil recovery, are already being practiced on a scale >0.05 Gt/year, little attention has been focused on the supply of CO2 for these projects. Here, facility-scale data newly collected by the U.S. Environmental Protection Agency was processed to produce the first comprehensive map of CO2 sources from industrial sectors currently supplying CO2 in the United States. Collectively these sources produce 0.16 Gt/year, but the data reveal the presence of large areas without access to CO2 at an industrially relevant scale (>25 kt/year). Even though some facilities with the capability to capture CO2 are not doing so and in some regions pipeline networks are being built to link CO2 sources and sinks, much of the country exists in "CO2 deserts". A life cycle analysis of the sources reveals that the predominant source of CO2, dedicated wells, has the largest carbon footprint further confounding prospects for rational carbon management strategies. PMID- 25137396 TI - Wood smoke enhances cigarette smoke-induced inflammation by inducing the aryl hydrocarbon receptor repressor in airway epithelial cells. AB - Our previous studies showed that cigarette smokers who are exposed to wood smoke (WS) are at an increased risk for chronic bronchitis and reduced lung function. The present study was undertaken to determine the mechanisms for WS-induced adverse effects. We studied the effect of WS exposure using four cohorts of mice. C57Bl/6 mice were exposed for 4 or 12 weeks to filtered air, to 10 mg/m(3) WS for 2 h/d, to 250 mg/m(3) cigarette smoke (CS) for 6 h/d, or to CS followed by WS (CW). Inflammation was absent in the filtered air and WS groups, but enhanced by twofold in the bronchoalveolar lavage of the CW compared with CS group as measured by neutrophil numbers and levels of the neutrophil chemoattractant, keratinocyte-derived chemokine. The levels of the anti-inflammatory lipoxin, lipoxin A4, were reduced by threefold along with cyclo-oxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1 in airway epithelial cells and PGE2 levels in the bronchoalveolar lavage of CW compared with CS mice. We replicated, in primary human airway epithelial cells, the changes observed in mice. Immunoprecipitations showed that WS blocked the interaction of aryl hydrocarbon receptor (AHR) with AHR nuclear transporter to reduce expression of COX-2 and mPGES-1 by increasing expression of AHR repressor (AHRR). Collectively, these studies show that exposure to low concentrations of WS enhanced CS-induced inflammation by inducing AHRR expression to suppress AHR, COX-2, and mPGES-1 expression, and levels of PGE2 and lipoxin A4. Therefore, AHRR is a potential therapeutic target for WS-associated exacerbations of CS-induced inflammation. PMID- 25137399 TI - Optimal data systems: the future of clinical predictions and decision support. AB - PURPOSE OF REVIEW: The purpose of the review is to describe the evolving concept and role of data as it relates to clinical predictions and decision-making. RECENT FINDINGS: Critical care medicine is, as an especially data-rich specialty, becoming acutely cognizant not only of its historic deficits in data utilization but also of its enormous potential for capturing, mining, and leveraging such data into well-designed decision support modalities as well as the formulation of robust best practices. SUMMARY: Modern electronic medical records create an opportunity to design complete and functional data systems that can support clinical care to a degree never seen before. Such systems are often referred to as 'data-driven,' but a better term is 'optimal data systems' (ODS). Here we discuss basic features of an ODS and its benefits, including the potential to transform clinical prediction and decision support. PMID- 25137400 TI - A history of outcome prediction in the ICU. AB - PURPOSE OF REVIEW: There are few first-hand accounts that describe the history of outcome prediction in critical care. This review summarizes the authors' personal perspectives about the development and evolution of Acute Physiology and Chronic Health Evaluation over the past 35 years. RECENT FINDINGS: We emphasize what we have learned in the past and more recently our perspectives about the current status of outcome prediction, and speculate about the future of outcome prediction. SUMMARY: There is increasing evidence that superior accuracy in outcome prediction requires complex modeling with detailed adjustment for diagnosis and physiologic abnormalities. Thus, an automated electronic system is recommended for gathering data and generating predictions. Support, either public or private, is required to assist users and to update and improve models. Current outcome prediction models have increasingly focused on benchmarks for resource use, a trend that seems likely to increase in the future. PMID- 25137401 TI - ICU severity of illness scores: APACHE, SAPS and MPM. AB - PURPOSE OF REVIEW: This review aims to evaluate the latest versions of the Acute Physiology and Chronic Health Evaluation, Simplified Acute Physiology Score and Mortality Probability Model scores, make comparisons and describe their strengths and limitations. Additionally, we provide critical analysis and recommendations for the use of these scoring systems in different scenarios. RECENT FINDINGS: The last generation of ICU scoring systems (Acute Physiology and Chronic Health Evaluation IV, Mortality Probability Model 0-III (MPM0-III) and Simplified Acute Physiology Score 3) was widely validated in different regions of the world and in distinct settings comprising general ICU patients as well as specific subgroups such as critically ill cancer patients, cardiovascular, surgical, acute kidney injury requiring renal replacement therapy and those in need of extra-corporeal membrane oxygen. Conflicting results are reported, and in general the scores presented a good discrimination despite a worse calibration as compared with the ones described in the original studies that generated them. Nonetheless, such calibration is often improved when customizations are performed both at ICU and region or country level. SUMMARY: ICU scoring systems provide a valuable framework to characterize patients' severity of illness for the evaluation of ICU performance, for quality improvement initiatives and for benchmarking purposes. However, to ensure the best accuracy, constant updates as well as regional customizations are required. PMID- 25137402 TI - Is there still a role for low-dose dopamine use in acute heart failure? AB - PURPOSE OF REVIEW: Acute heart failure (AHF) is a major health problem worldwide, with no proven therapy. Low-dose dopamine has been used in this entity to improve renal outcomes in the past decades. The aim of this article is to review the former and recent clinical trials about the use of low-dose dopamine in AHF. RECENT FINDINGS: The Dopamine in Acute Decompensated Heart Failure II study enrolled 161 patients with AHF and found no improvement in clinical outcomes with the addition of dopamine. Similarly, the Renal Optimization Strategies Evaluation in Acute Heart Failure trial, which included 360 patients with AHF and renal dysfunction, evaluated the efficacy of 72-h infusion of either low-dose nesiritide or low-dose dopamine versus placebo in addition to standardized diuretic treatment. No differences were found between both treatment groups and placebo with regard to the coprimary endpoints of cumulative urine volume and change from baseline in plasma cystatin C. SUMMARY: On the basis of the current data, there is no role for the routine use of low-dose dopamine in nonhypotensive patients with AHF. Further studies are needed to define the role of low-dose dopamine in patients with AHF and hypotension. Until the availability of more data, the use of dopamine in AHF should be individualized. PMID- 25137403 TI - Predicting outcome in critical care: past, present and future. PMID- 25137404 TI - (001) SrTiO3 | (001) MgO interface and oxygen-vacancy stability from first principles calculations. AB - In-depth understanding of interfacial atomistic structures is required to design heterointerfaces with controlled functionalities. Using density functional theory calculations, we investigate the interfacial structure of (001) SrTiO3 | (001) MgO, and characterize the stable interface structure. Among the four types of possible interface structures, we show that the TiO2-terminated SrTiO3 containing electrostatically attractive Mg-O and Ti-O ion-ion interactions forms the most stable interface. We also show that oxygen vacancies can be preferentially stabilized across the interface via manipulating interfacial strain. We elucidate that oxygen vacancies are most stable in the tensile-strain material, and unstable in compressive strain material. This stability is explained from equation-of-state analysis using a single crystal, where the oxygen vacancy shows a larger volume than the oxygen ion, thus explaining its stability under tensile strained conditions. PMID- 25137405 TI - Label free detection of specific protein binding using a microwave sensor. AB - The specific binding of streptavidin to biotinylated protein A was demonstrated using a microwave detection system. In control experiments, the degree of non specific binding was negligible. The method of detection was used to monitor the adsorption of two other proteins, cytochrome c and glucose oxidase, on to the IDE microwave sensor surface. The response of the sensor was also examined on different substrate materials, with detection of protein binding observed obtained on both smooth, conductive (gold) and on rough, insulating (hydroxyapatite) surfaces. PMID- 25137406 TI - R-134a (1,1,1,2-Tetrafluoroethane) Inhalation Induced Reactive Airways Dysfunction Syndrome. AB - R-134a (1,1,1,2-tetrafluoroethane) is widely used as a refrigerant and as an aerosol propellant. Inhalation of R-134a can lead to asphyxia, transient confusion, and cardiac arrhythmias. We report a case of reactive airways dysfunction syndrome secondary to R-134a inhalation. A 60-year-old nonsmoking man without a history of lung disease was exposed to an air conditioner refrigerant spill while performing repairs beneath a school bus. Afterward, he experienced worsening shortness of breath with minimal exertion, a productive cough, and wheezing. He was also hypoxic. He was admitted to the hospital for further evaluation. Spirometry showed airflow obstruction with an FEV1 1.97 L (45% predicted). His respiratory status improved with bronchodilators and oral steroids. A repeat spirometry 2 weeks later showed improvement with an FEV1 2.5 L (60% predicted). Six months after the incident, his symptoms had improved, but he was still having shortness of breath on exertion and occasional cough. PMID- 25137407 TI - Polyhydroxybutyrate-coated magnetic nanoparticles for doxorubicin delivery: cytotoxic effect against doxorubicin-resistant breast cancer cell line. AB - In this study, polyhydroxybutyrate (PHB)-coated magnetic nanoparticles (MNPs) were prepared by coprecipitation of iron salts (Fe and Fe) by ammonium hydroxide. Characterizations of PHB-coated MNPs were performed by Fourier transform infrared spectroscopy, x-ray diffraction, dynamic light scattering, thermal gravimetric analysis, vibrating sample magnetometry, and transmission electron microscopy analyses. Doxorubicin was loaded onto PHB-MNPs, and the release efficiencies at different pHs were studied under in vitro conditions. The most efficient drug loading concentration was found about 87% at room temperature in phosphate buffered saline (pH 7.2). The drug-loaded MNPs were stable up to 2 months in neutral pH for mimicking physiological conditions. The drug release studies were performed with acetate buffer (pH 4.5) that mimics endosomal pH. Doxorubicin (60%) released from PHB-MNPs within 65 hours. Doxorubicin-loaded PHB-MNPs were about 2.5-fold more cytotoxic as compared with free drug on resistant Michigan Cancer Foundation-7 (human breast adenocarcinoma, MCF-7) cell line (1 MUM doxorubicin) in vitro. Therefore, doxorubicin-loaded PHB-MNPs lead to overcome the drug resistance. PMID- 25137408 TI - Nicotinic Acid and new-onset diabetes. PMID- 25137409 TI - Maternal plasma DNA testing: experience of women counseled at a prenatal diagnosis center. AB - AIMS: To evaluate the early introduction of circulating cell-free (ccf) DNA testing in a prenatal diagnosis center serving a statewide population. RESULTS: A retrospective chart review of patients at high aneuploidy risk counseled during the two 10-week periods that documents indication, risk, maternal age, insurance coverage, decisions, and reasoning behind that decision. Among the 299 included women, indication was advanced maternal age (17% with and 56% without an additional indication), positive serum screen (15%), and abnormal ultrasound (12%). Uptake increased from 10% to 17%, as did patient awareness of the test (4% to 14%). Women with lower copayments were more likely to complete testing (23% vs. 5%, p<0.001). Most women completing testing (75%) wanted to avoid an invasive procedure, while those declining cited testing would not change anything (47%), preferred diagnostic testing (16%), negative follow-up testing (20%), and cost/insurance issues (9%). One of 42 tests was positive (trisomy 21). CONCLUSIONS: Individual patient follow-up allows us to document ccfDNA-related patient decision-making. Nearly half of the women did not want further testing and one in seven preferred immediate diagnostic testing. Patient costs were a barrier to testing that, if avoided, could increase test uptake by 50% or more. PMID- 25137410 TI - AgONO-assisted direct C-H arylation of heteroarenes with anilines. AB - A novel copper-catalyzed C-H arylation of heteroarenes with anilines by an in situ diazonium reaction is established by using silver nitrite (AgONO) as an unconventional nitrosating reagent under acid-free conditions. It provides a complementary approach for the C-H arylation of electron-rich heteroarenes with aromatic amines affording a variety of heterobiaryls in moderate to good yields. PMID- 25137411 TI - Upregulated plasma and urinary levels of nucleosides as biological markers in the diagnosis of primary gallbladder cancer. AB - We first detected aberrant nucleoside levels in the plasma, urine, bile, and tissues from cases and controls to explore them as biomarkers in the diagnosis of gallbladder cancer. Reversed-phase high-performance liquid chromatography was used to assess the levels of ten nucleosides in these samples from gallbladder cancer patients, gallstone patients, and healthy controls. Plasma and urine samples were collected from patients with gallbladder cancer (n = 202), patients with gallstones (n = 203), and healthy controls (n = 205); bile and tissue samples were collected from 91 gallbladder cancer patients, 93 gallstone patients; and 90 were donated after cardiac death. Of the ten nucleosides analyzed, eight urinary nucleosides, five plasma nucleosides, three bile nucleosides, and one tissue nucleoside were significantly upregulated in the gallbladder cancer patients compared to control groups (p < 0.05). Among these upregulated nucleosides, the sensitivity, specificity, and accuracy of urinary nucleosides in the diagnosis of gallbladder cancer patients were 89.4, 97.1, and 95.7%, respectively, those of plasma nucleosides were 91.2, 95.6, and 94.2%, respectively, those of bile nucleosides were 95.3, 96.4, and 95.1%, respectively, and those of tissue nucleosides were 86.2, 93.8, and 92.6%, respectively. These results suggest that nucleosides may be as useful as biological markers for gallbladder cancer. PMID- 25137412 TI - Classification algorithms for the identification of structural injury in TBI using brain electrical activity. AB - BACKGROUND: There is an urgent need for objective criteria adjunctive to standard clinical assessment of acute Traumatic Brain Injury (TBI). Details of the development of a quantitative index to identify structural brain injury based on brain electrical activity will be described. METHODS: Acute closed head injured and normal patients (n=1470) were recruited from 16 US Emergency Departments and evaluated using brain electrical activity (EEG) recorded from forehead electrodes. Patients had high GCS (median=15), and most presented with low suspicion of brain injury. Patients were divided into a CT positive (CT+) group and a group with CT negative findings or where CT scans were not ordered according to standard assessment (CT-/CT_NR). Three different classifier methodologies, Ensemble Harmony, Least Absolute Shrinkage and Selection Operator (LASSO), and Genetic Algorithm (GA), were utilized. RESULTS: Similar performance accuracy was obtained for all three methodologies with an average sensitivity/specificity of 97.5%/59.5%, area under the curves (AUC) of 0.90 and average Negative Predictive Validity (NPV)>99%. Sensitivity was highest for CT+ cases with potentially life threatening hematomas, where two of three classifiers were 100%. CONCLUSION: Similar performance of these classifiers suggests that the optimal separation of the populations was obtained given the overlap of the underlying distributions of features of brain activity. High sensitivity to CT+ injuries (highest in hematomas) and specificity significantly higher than that obtained using ED guidelines for imaging, supports the enhanced clinical utility of this technology and suggests the potential role in the objective, rapid and more optimal triage of TBI patients. PMID- 25137413 TI - Induction of highly functional hepatocytes from human umbilical cord mesenchymal stem cells by HNF4alpha transduction. AB - AIM: To investigate the differentiation potential of human umbilical mesenchymal stem cells (HuMSCs) and the key factors that facilitate hepatic differentiation. METHODS: HuMSCs were induced to become hepatocyte-like cells according to a previously published protocol. The differentiation status of the hepatocyte-like cells was examined by observing the morphological changes under an inverted microscope and by immunofluorescence analysis. Hepatocyte nuclear factor 4 alpha (HNF4alpha) overexpression was achieved by plasmid transfection of the hepatocyte like cells. The expression of proteins and genes of interest was then examined by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods. RESULTS: Our results demonstrated that HuMSCs can easily be induced into hepatocyte-like cells using a published differentiation protocol. The overexpression of HNF4alpha in the induced HuMSCs significantly enhanced the expression levels of hepatic-specific proteins and genes. HNF4alpha overexpression may be associated with liver-enriched transcription factor networks and the Wnt/beta-Catenin pathway. CONCLUSION: The overexpression of HNF4alpha improves the hepatic differentiation of HuMSCs and is a simple way to improve cellular sources for clinical applications. PMID- 25137414 TI - Resting state functional connectivity of the anterior cingulate cortex in veterans with and without post-traumatic stress disorder. AB - Post-traumatic stress disorder (PTSD) is an anxiety disorder that is associated with structural and functional alterations in several brain areas, including the anterior cingulate cortex (ACC). Here, we examine resting state functional connectivity of ACC subdivisions in PTSD, using a seed-based approach. Resting state magnetic resonance images were obtained from male veterans with (n = 31) and without (n = 25) PTSD, and healthy male civilian controls (n = 25). Veterans with and without PTSD (combat controls) had reduced functional connectivity compared to healthy controls between the caudal ACC and the precentral gyrus, and between the perigenual ACC and the superior medial gyrus and middle temporal gyrus. Combat controls had increased connectivity between the rostral ACC and precentral/middle frontal gyrus compared to PTSD patients and healthy civilian controls. The resting state functional connectivity differences in the perigenual ACC network reported here indicate that veterans differ from healthy controls, potentially due to military training, deployment, and/or trauma exposure. In addition, specific alterations in the combat controls may potentially be related to resilience. These results underline the importance of distinguishing trauma exposed (combat) controls from healthy civilian controls when studying PTSD. PMID- 25137415 TI - A nationwide 2010-2012 analysis of U.S. health care utilization in inflammatory bowel diseases. AB - BACKGROUND: Implementation of the 2010 Affordable Care Act (ACA) calls for a collaborative effort to transform the U.S. health care system toward patient centered and value-based care. To identify how specialty care can be improved, we mapped current U.S. health care utilization in patients with inflammatory bowel diseases (IBD) using a national insurance claims database. METHODS: We performed a cross-sectional study analyzing U.S. health care utilization in 964,633 patients with IBD between 2010 and 2012 using insurance claims data, including pharmacy and medical claims. Frequency of IBD-related care utilization (medication, tests, and treatments) and their charges were evaluated. Subsequently, outcomes were put into the framework of current U.S. guidelines to identify areas of improvement. RESULTS: A disproportionate usage of aminosalicylates in Crohn's disease (42%), frequent corticosteroid use (46%, with 9% long-term users), and low rates of corticosteroid-sparing drugs (thiopurines 15%; methotrexate 2.7%) were observed. Markers for inflammatory activity, such as C-reactive protein or fecal calprotectin were not commonly used (8.8% and 0.13%, respectively). Although infrequently used (11%), anti-TNF antibody therapy represents a major part of observed IBD charges. CONCLUSIONS: This analysis shows 2010-2012 utilization and medication patterns of IBD health care in the United States and suggests that improvement can be obtained through enhanced guidelines adherence. PMID- 25137416 TI - Disease course and management strategy of pouch neoplasia in patients with underlying inflammatory bowel diseases. AB - BACKGROUND: To evaluate the disease course and management strategy for pouch neoplasia. METHODS: Patients undergoing ileal pouch surgery for underlying ulcerative colitis who developed low-grade dysplasia (LGD), high-grade dysplasia, or adenocarcinoma in the pouch were identified. RESULTS: All eligible 44 patients were evaluated. Of the 22 patients with initial diagnosis of pouch LGD, 6 (27.3%) had persistence or progression after a median follow-up of 9.5 (4.1-17.6) years. Family history of colorectal cancer was shown to be a risk factor associated with persistence or progression of LGD (P = 0.03). Of the 12 patients with pouch high grade dysplasia, 5 (41.7%) had a history of (n = 2, 16.7%) or synchronous (n = 4, 33.3%) pouch LGD. Pouch high-grade dysplasia either persisted or progressed in 3 patients (25.0%) after the initial management, during a median time interval of 5.4 (2.2-9.2) years. Of the 14 patients with pouch adenocarcinoma, 12 (85.7%) had a history of (n = 2, 14.3%) or synchronous dysplasia (n = 12, 85.7%). After a median follow-up of 2.1 (0.6-5.2) years, 6 patients with pouch cancer (42.9%) died. Comparison of patients with a final diagnosis of pouch adenocarcinoma (14, 32.6%), and those with dysplasia (29, 67.4%) showed that patients with adenocarcinoma were older (P = 0.04) and had a longer duration from IBD diagnosis or pouch construction to the detection of pouch neoplasia (P = 0.007 and P = 0.0013). CONCLUSIONS: The risk for progression of pouch dysplasia can be stratified. The presence of family history of colorectal cancer seemed to increase the risk for persistence or progression for patients with pouch LGD. The prognosis for pouch adenocarcinoma was poor. PMID- 25137417 TI - Barriers and facilitators to successful transition from pediatric to adult inflammatory bowel disease care from the perspectives of providers. AB - BACKGROUND: For adolescents and young adults (AYA) with inflammatory bowel disease (IBD), the transition from pediatric to adult care is often challenging and associated with gaps in care. Our study objectives were to (1) identify outcomes for evaluating transition success and (2) elicit the major barriers and facilitators of successful transition. METHODS: We interviewed pediatric and adult IBD providers from across the United States with experience caring for AYAs with IBD until thematic saturation was reached after 12 interviews. We elicited the participants' backgrounds, examples of successful and unsuccessful transition of AYAs for whom they cared, and recommendations for improving transition using the Social-Ecological Model of Adolescent and Young Adult Readiness to Transition framework. We coded interview transcripts using the constant comparative method and identified major themes. RESULTS: Participants reported evaluating transition success and failure using health care utilization outcomes (e.g., maintaining continuity with adult providers), health outcomes (e.g., stable symptoms), and quality of life outcomes (e.g., attending school). The patients' level of developmental maturity (i.e., ownership of care) was the most prominent determinant of transition outcomes. The style of parental involvement (i.e., helicopter parent versus optimally involved parent) and the degree of support by providers (e.g., care coordination) also influenced outcomes. CONCLUSIONS: IBD transition success is influenced by a complex interplay of patient developmental maturity, parenting style, and provider support. Multidisciplinary IBD care teams should aim to optimize these factors for each patient to increase the likelihood of a smooth transfer to adult care. PMID- 25137418 TI - Assessment of histologic disease activity in Crohn's disease: a systematic review. AB - BACKGROUND: Crohn's disease (CD) is an idiopathic, chronic, transmural inflammatory disorder of the gastrointestinal tract. Because mucosal involvement is near-universal, endoscopic healing has emerged as an important aspect in improving outcome. However, resolution of histologic disease activity has potential to convey additional benefit beyond that attained with endoscopic healing alone. Validated scoring systems of histologic disease activity are required to further assess this possibility. The aim of this study was to systematically review the existing histologic disease activity indices (HDAI) for CD and to assess their operating properties and potential use as outcome measures in clinical trials. METHODS: MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Disease Week (DDW) abstracts were searched from 1981 to April 2013 for applicable studies to identify relevant studies for review and analysis. RESULTS: In total, 3732 citations were screened to obtain 89 articles for inclusion. Sixty-six HDAIs were characterized as either stepwise or numerical instruments. These HDAIs were used for either assessment of response to medical therapy or for comparison with biomarkers or imaging tests. None of the HDAIs identified was developed according to currently accepted methods for developing evaluative instruments, and none have been formally validated. CONCLUSIONS: Measurement of histologic disease activity has potential value in CD; however, no validated measures are available. Additional research is needed to develop a methodologically rigorous instrument for use in clinical investigation and potentially for clinical practice. PMID- 25137421 TI - Serum androgen levels in elite female athletes. AB - OBJECTIVE: Prior to the implementation of the blood steroidal module of the Athlete Biological Passport, we measured the serum androgen levels among a large population of high-level female athletes as well as the prevalence of biochemical hyperandrogenism and some disorders of sex development (DSD). METHODS AND RESULTS: In 849 elite female athletes, serum T, dehydroepiandrosterone sulphate, androstenedione, SHBG, and gonadotrophins were measured by liquid chromatography mass spectrometry high resolution or immunoassay. Free T was calculated. The sampling hour, age, and type of athletic event only had a small influence on T concentration, whereas ethnicity had not. Among the 85.5% that did not use oral contraceptives, 168 of 717 athletes were oligo- or amenorrhoic. The oral contraceptive users showed the lowest serum androgen and gonadotrophin and the highest SHBG concentrations. After having removed five doped athletes and five DSD women from our population, median T and free T values were close to those reported in sedentary young women. The 99th percentile for T concentration was calculated at 3.08 nmol/L, which is below the 10 nmol/L threshold used for competition eligibility of hyperandrogenic women with normal androgen sensitivity. Prevalence of hyperandrogenic 46 XY DSD in our athletic population is approximately 7 per 1000, which is 140 times higher than expected in the general population. CONCLUSION: This is the first study to establish normative serum androgens values in elite female athletes, while taking into account the possible influence of menstrual status, oral contraceptive use, type of athletic event, and ethnicity. These findings should help to develop the blood steroidal module of the Athlete Biological Passport and to refine more evidence-based fair policies and recommendations concerning hyperandrogenism in female athletes. PMID- 25137423 TI - Elevated FGF21 leads to attenuated postnatal linear growth in preterm infants through GH resistance in chondrocytes. AB - CONTEXT: The hormone fibroblast growth factor 21 (FGF21) is a key metabolic regulator in the adaptation to fasting. In food-restricted mice, inhibition of skeletal growth is mediated by the antagonistic effect of FGF21 on GH action in the liver and growth plate. OBJECTIVE: The objective of the study was to assess the role of FGF21 in growth regulation in humans using postnatal growth failure of very preterm infants as a model. DESIGN: FGF21 levels were measured serially in very preterm infants, and their linear growth evaluated from birth to term equivalent age. Primary chondrocytes obtained from pediatric donors were used to test whether FGF21 can directly interfere with GH signaling. RESULTS: A negative association (beta -.415, P < .005, linear regression model) of FGF21 levels with the change in SD score for length was found. In primary chondrocytes, FGF21 upregulated basal and GH-induced SOCS2 expression and inhibited GH-induced signal transducer and activator of transcription 5 (STAT5) phosphorylation as well as GH induced COLII and ALP expression. Finally, FGF21 inhibited GH-induced IGF-1 expression and cell proliferation, indicating GH resistance. However, FGF21 did not affect IGF-1-induced cell proliferation. CONCLUSIONS: Elevated FGF21 serum levels during the first weeks of life are independently associated with postnatal growth failure in preterm infants. Furthermore, our data provide mechanistic insights into GH resistance secondary to prematurity and may offer an explanation for the growth failure commonly seen in chronic conditions of childhood. PMID- 25137422 TI - Parathyroid hormone 1-84 alters circulating vascular endothelial growth factor levels in hypoparathyroidism. AB - CONTEXT: We previously reported on four patients treated with PTH(1-84) who recovered from postoperative hypoparathyroidism many years after onset. Because vascular endothelial growth factor (VEGF) has been shown to be necessary for the induction of PTH-mediated angiogenesis, we postulated a possible role for VEGF in the recovery of parathyroid function in these subjects. OBJECTIVE: Our objective was to measure VEGF levels in subjects with hypoparathyroidism who regained parathyroid gland function and matched controls. SETTING AND DESIGN: Subjects with hypoparathyroidism who regained parathyroid gland function were each matched to two hypoparathyroid controls by postoperative etiology, age (within 5 y), menopausal status, and duration of hypoparathyroidism. We measured serum VEGF levels at baseline and through 48 months of PTH(1-84) therapy. RESULTS: VEGF levels increased after the initiation of PTH(1-84) therapy for the entire cohort, from 309.7 +/- 162 pg/ml at baseline to 380.2 +/- 178 pg/ml at 12 months (P = .03). Levels trended downward thereafter. There were no significant differences in VEGF levels between the subjects with recovery of parathyroid function and the matched controls. CONCLUSIONS: PTH(1-84) alters serum VEGF levels in subjects with hypoparathyroidism. Additional investigation is necessary to understand the mechanisms by which some subjects with postoperative hypoparathyroidism recover parathyroid gland function. PMID- 25137420 TI - Genetic risk score for prediction of newborn adiposity and large-for-gestational age birth. AB - CONTEXT: Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes. OBJECTIVE: This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth. SETTING AND DESIGN: Single nucleotide polymorphisms (SNPs) in 40 regions associated with adult obesity-related traits were tested for association with newborn size. GRS's for birth weight and sum of skinfolds (SSF) specific to ancestry were calculated using the most highly associated SNP for each ancestry in genomic regions with one or more SNPs associated with birth weight and/or SSF in at least one ancestry group or meta-analyses. PARTICIPANTS: Newborns from the Hyperglycemia Adverse Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern European, 573 Mexican-American, and 1182 Thai). OUTCOME MEASURES: Birth weight >90th percentile (LGA) and newborn SSF >90th percentile were primary outcomes. RESULTS: After adjustment for ancestry, sex, gestational age at delivery, parity, maternal genotype, maternal smoking/alcohol intake, age, body mass index, height, blood pressure and glucose, 25 and 23 SNPs were associated (P < .001) with birth weight and newborn SSF, respectively. The GRS was highly associated with both phenotypes as continuous variables across all ancestries (P <= 1.6 * 10(-19)) and improved prediction of birth weight and SSF >90th percentile when added to a baseline model incorporating the covariates listed above. CONCLUSIONS: A GRS comprised of SNPs associated with adult obesity-related traits may provide an approach for predicting LGA birth and newborn adiposity beyond established risk factors. PMID- 25137424 TI - Intra-tissue steroid profiling indicates differential progesterone and testosterone metabolism in the endometrium and endometriosis lesions. AB - CONTEXT: Aberrant sex steroid signaling is suggested to promote endometriosis growth by several mechanisms, and the tissue concentrations of sex steroids are key determinants of the hormone action. However, their concentrations are only superficially known in the endometrium and endometriosis lesions. OBJECTIVE: This study sought to evaluate whether the tissue steroid hormone concentrations in endometriosis differ from the endometrium or serum. MAIN OUTCOME MEASURES: Steroid analysis of serum and tissue specimens of women with endometriosis (n = 60) and healthy controls (n=16) was measured, and supporting data from quantitative RT-PCR for steroidogenic enzymes and explant cultures of a subset of specimens is provided. RESULTS: Endometrial tissue progesterone (P4) concentrations reflected the serum P4 levels during the menstrual cycle, whereas in endometriosis lesions, the cycle-dependent change was missing. Remarkably high tissue T concentrations were measured in endometriosis lesions independent of the cycle phase, being 5-19 times higher than the corresponding serum levels. Tissue/serum ratio of T was further increased in patients with contraceptive medication. The altered tissue steroid concentrations in endometriosis were in line with the expression of various steroidogenic enzymes in the lesions, of which HSD3B2 showed constantly high expression, whereas CYP11A1 expression was low. Furthermore, the high concentration of sex steroids detected in the ovarian lesions involves their production by the lesion and by the adjacent ovarian tissue. CONCLUSIONS: Endometriosis lesions present with progestin and androgen metabolism, which are different from that of the endometrium, and the lesions are characterized by high tissue T and a loss of cyclical changes in tissue P4 concentration. PMID- 25137425 TI - No improvement of high-density lipoprotein (HDL) vasorelaxant effect despite increase in HDL cholesterol concentration in type 2 diabetic patients treated with glitazones. AB - CONTEXT: High-density lipoproteins (HDLs) from type 2 diabetic patients are unable to counteract the inhibitory effect of oxidized low-density lipoproteins (ox-LDLs) on vasorelaxation. We hypothesized that glitazones, which improve glycemic control and dyslipidemia, could correct this abnormality. OBJECTIVES AND DESIGN: We compared the ability of HDL from controls (n = 12) and from type 2 diabetic patients before and after 6 months of treatment with either rosiglitazone (n = 11) or pioglitazone (n = 8) to counteract the inhibitory effect of ox-LDL on vasodilatation of rabbit aorta rings. RESULTS: Rosiglitazone induced a decrease in hemoglobin A1c (7.7% +/- 1.1% vs 9.8% +/- 1.0%, P = .003) and an increase in HDL cholesterol (1.14 +/- 0.32 vs 0.98 +/- 0.24 mmol/L, P = .033). Pioglitazone induced a decrease in hemoglobin A1c (8.3% +/- 2.5% vs 9.5% +/- 3.2%, P = .068) and serum triglycerides (1.58 +/- 0.89 vs 2.03 +/- 0.70 mmol/L, P = .069) and an increase in HDL cholesterol (1.39 +/- 0.22 vs 1.14 +/- 0.22 mmol/L, P = .018). The triglyceride content of HDL was unchanged by rosiglitazone and was decreased by 25% (P = .068) by pioglitazone. HDL from controls counteracted the inhibitory effect of ox-LDL on vasodilatation (maximal relaxation [Emax] = 74.4% +/- 3.5% vs 51.9% +/- 3.3%, P = .0029), whereas HDL from type 2 diabetic patients did not (Emax = 51.7% +/- 5.8% vs 52.3% +/- 4.6% [P = .66] and 52.7% +/- 5.5% vs 51.9% +/- 4.5% [P = .78] for the rosiglitazone and pioglitazone group, respectively). Rosiglitazone or pioglitazone did not improve Emax (58.6% +/- 5.9% vs 52.3% +/- 4.6% [P = .15] and 49.3% +/- 6.5% vs 51.9% +/- 4.5% [P = .48], respectively). CONCLUSION: Glitazones increased the concentration of HDL cholesterol without restoring the ability of HDL particles to protect the endothelium from oxidative stress-induced dysfunction, meaning that HDL remained dysfunctional with impaired antiatherogenic properties. PMID- 25137426 TI - Comprehensive next-generation sequencing analyses of hypoparathyroidism: identification of novel GCM2 mutations. AB - CONTEXT: In most patients with hypoparathyroidism (HP), the etiology is not defined clinically. Eight genes (AIRE, CASR, CLDN16, GATA3, GCM2, PTH, TBCE, and TRPM6) are known to be responsible genes associated with HP; however, no previous study has screened the eight responsible genes comprehensively in HP patients. OBJECTIVES: This study was conducted to determine the genetic defect in HP patients. We also described clinical and molecular findings of two HP patients with novel GCM2 mutations. SUBJECTS AND METHODS: We enrolled 20 nonconsanguineous Japanese patients with child-onset permanent HP without 22q11 deletion. Mutations and genomic rearrangements involving the eight genes were screened by targeted next-generation sequencing (NGS). We also screened genetic rearrangements by array comparative genomic hybridization (aCGH) in the mutation-negative patients. A putative deletion, which was suspected by NGS, was additionally analyzed by droplet digital PCR (ddPCR) and junction PCR. Identified novel nucleotide-level GCM2 mutants were characterized in vitro. RESULTS: We identified seven patients with a single gene disorder, including a CASR mutation, GATA3 mutations, and novel GCM2 mutations (R367Tfs*15, T370M, and the deletion encompassing exon 1). This submicroscopic deletion, which had been suspected by NGS, could not be detected by aCGH and was confirmed by ddPCR and junction PCR. Functional studies of R367Tfs*- and T370M-GCM2 demonstrated a reduction of target gene transactivation in both. CONCLUSIONS: Using comprehensive NGS analyses, we identified the genetic defect in 35% of HP patients in our cohort and discovered novel GCM2 mutations including submicroscopic deletion that was undetectable by aCGH. PMID- 25137429 TI - Impact factor for 2013. PMID- 25137428 TI - Letrozole vs anastrozole for height augmentation in short pubertal males: first year data. AB - CONTEXT: Aromatase inhibitors are used off-label to treat short stature in peripubertal boys. OBJECTIVE: To investigate short- and long-term hormonal and auxologic differences in short pubertal boys treated with letrozole (L) or anastrozole (A). DESIGN: PATIENTS are seen for laboratory evaluation and physical examination every 6 months, bone age yearly, DEXA and spine film every 2 years. They will be followed until they reach their final height. This is a preliminary report after 1 year of treatment. SETTING: A single academic children's hospital outpatient clinic. PATIENTS: Boys with age >10 years, bone age <= 14 years, clinical and hormonal evidence of central puberty, and either height < fifth percentile or predicted adult height (PAH) more than 10 cm below mid-parental height (MPH). INTERVENTION: Letrozole (2.5 mg) or anastrozole (1 mg) was administered orally each day. MAIN OUTCOME MEASURES: Hormonal and clinical parameters, growth velocity, and change in bone age and PAH. RESULTS: Thirty-nine boys have completed 1 year of treatment. Baseline means were age 14.1 years, PAH 166 cm, and testosterone 198 ng/dL. At 1 year, letrozole resulted in higher LH (L 6.1 +/- 2.5 vs A 3.2 +/- 1.7 IU/L) and testosterone (1038 +/- 348 vs 536 +/- 216 ng/dL) with lower estradiol (2.8 +/- 2.8 vs 5.6 +/- 2.9 pg/mL) and IGF-1 (237 +/- 51 vs 331 +/- 79 ng/mL). First year growth velocities were identical (7.2 cm/year), but an increase in PAH was greater in the anastrozole group (4.2 +/- 3.5 vs 1.4 +/- 4.4 cm, p = 0.03) after 1 year. CONCLUSIONS: We present first-year data from a direct comparison of anastrozole and letrozole for height augmentation in short pubertal boys. Letrozole was more potent in hormonal manipulation than anastrozole. First-year growth velocities were comparable, but improvement in PAH was greater in the anastrozole group. It remains to be seen if positive PAH trends will translate to increase in final height in either group. PMID- 25137427 TI - Prospective study of surgical treatment of acromegaly: effects on ghrelin, weight, adiposity, and markers of CV risk. AB - CONTEXT: Although epidemiological studies have found that GH and IGF-1 normalization reduce the excess mortality of active acromegaly to expected rates, cross-sectional data report some cardiovascular (CV) risk markers to be less favorable in remission than active acromegaly. OBJECTIVE: The objective of the study was to test the hypothesis that remission of acromegaly after surgical therapy increases weight and adiposity and some CV risk markers and these changes are paralleled by a rise in ghrelin. DESIGN: Forty-two adults with untreated, active acromegaly were studied prospectively. Changes in outcome measures from before to after surgery were assessed in 26 subjects achieving remission (normal IGF-1) and 16 with persistent active acromegaly (elevated IGF-1) after surgery. SETTING: The study was conducted at tertiary referral centers for pituitary tumors. MAIN OUTCOME MEASURES: Endocrine, metabolic, and CV risk parameters, anthropometrics, and body composition by dual-energy X-ray absorptiometry were measured. RESULTS: Remission increased total ghrelin, body weight, waist circumference, C-reactive protein, homocysteine, high-density lipoprotein, and leptin and reduced systolic blood pressure, homeostasis model assessment score, triglycerides, and lipoprotein (a) by 6 months and for 32 +/- 4 months after surgery. The ghrelin rise correlated with the fall in the levels of GH, IGF-1, and insulin and insulin resistance. Weight, waist circumference, and ghrelin did not increase significantly in the persistent active acromegaly group. Total body fat, trunk fat, and perentage total body fat increased by 1 year after surgery in 15 remission subjects: the increase in body fat correlated with the rise in total ghrelin. CONCLUSIONS: Although most markers of CV risk improve with acromegaly remission after surgery, some markers and adiposity increase and are paralleled by a rise in total ghrelin, suggesting that these changes may be related. Understanding the mechanisms and long-term implications of the changes that accompany treatment of acromegaly is important to optimizing management because some aspects of the postoperative profile associate with the increased metabolic and CV risk in other populations. PMID- 25137430 TI - The effect of dexmedetomidine on intraocular pressure increase in patients during robot-assisted laparoscopic radical prostatectomy in the steep Trendelenburg position. AB - PURPOSE: This study was to evaluate the effect of intraoperative continuous infusion of dexmedetomidine on intraocular pressure (IOP) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALRP) in the steep Trendelenburg (ST). MATERIALS AND METHODS: Sixty-eight patients were randomly divided into two groups. The dexmedetomidine group (Group D, n=34) received a continuous infusion of dexmedetomidine at a rate of 0.4 MUg kg(-1) hour(-1) from the induction of anesthesia until the end of the ST position, while the control group (Group C, n=34) received an equal volume of physiologic saline at the same rate under conventional general anesthesia with sevoflurane and remifentanil. IOP was measured at 11 predefined time points for all patients. RESULTS: Significant differences in IOP were detected between the two groups by a linear mixed model analysis (p<0.001). The highest mean IOP was 19.9+/-5.0 mm Hg in Group D and 25.7+/-5.0 mm Hg in Group C; both were measured 60 minutes after the patients had been placed in the ST position. No significant between-group differences in ocular perfusion pressure, mean blood pressure, or heart rate were observed between the two groups. No ocular or other complications were noted. CONCLUSION: Intraoperative continuous infusion of dexmedetomidine may help alleviate IOP increase in patients undergoing RALRP in the ST position. PMID- 25137431 TI - Correction of the deviated septum: from ancient Egypt to the endoscopic era. AB - BACKGROUND: Obstructed nasal breathing can occur due to deviation of the nasal septum. When the external nose appears grossly normal and cosmesis is not the focus, septoplasty has been the procedure used to straighten the septum with the goal of improving nasal airflow. Septoplasty has evolved over time. METHODS: A historical literature review was conducted to look for primary source journal articles and medical conferences proccedings addressing the evolution of the septoplasty procedure. RESULTS: Early techniques involved forcible fractures and splinting. Submucous resection was the first major advancement in surgical technique. Once the complications resulting from this technique were observed, it was subsequently revised with attempts to better address the caudal septal deviation. Attention was then turned to better incorporating the role surrounding support structures, such as the upper lateral cartilages. The premaxilla-maxilla approach attempted to address the overall nasal structure to best improve nasal breathing. The advent of endoscopic technique has been the most recent shift in surgical technique with improved visualization allowing for targeted septoplasty and reoperation on complicated cases including pituitary and skull base surgery. CONCLUSION: This paper discusses the evolution of septoplasty techniques over time from the initial undertakings of the ancient Egyptians to the modern-day septoplasty. While the principles behind septoplasty have remained much the same, experience has allowed for refinement of surgical technique. No doubt new instrumentations and innovations will further help to tailor the practice of septoplasty to the anatomy and functional needs of each individual patient. PMID- 25137433 TI - Enhanced electrochemical methanation of carbon dioxide with a dispersible nanoscale copper catalyst. AB - Although the vast majority of hydrocarbon fuels and products are presently derived from petroleum, there is much interest in the development of routes for synthesizing these same products by hydrogenating CO2. The simplest hydrocarbon target is methane, which can utilize existing infrastructure for natural gas storage, distribution, and consumption. Electrochemical methods for methanizing CO2 currently suffer from a combination of low activities and poor selectivities. We demonstrate that copper nanoparticles supported on glassy carbon (n-Cu/C) achieve up to 4 times greater methanation current densities compared to high purity copper foil electrodes. The n-Cu/C electrocatalyst also exhibits an average Faradaic efficiency for methanation of 80% during extended electrolysis, the highest Faradaic efficiency for room-temperature methanation reported to date. We find that the level of copper catalyst loading on the glassy carbon support has an enormous impact on the morphology of the copper under catalytic conditions and the resulting Faradaic efficiency for methane. The improved activity and Faradaic efficiency for methanation involves a mechanism that is distinct from what is generally thought to occur on copper foils. Electrochemical data indicate that the early steps of methanation on n-Cu/C involve a pre equilibrium one-electron transfer to CO2 to form an adsorbed radical, followed by a rate-limiting non-electrochemical step in which the adsorbed CO2 radical reacts with a second CO2 molecule from solution. These nanoscale copper electrocatalysts represent a first step toward the preparation of practical methanation catalysts that can be incorporated into membrane-electrode assemblies in electrolyzers. PMID- 25137434 TI - Development of nanodroplets for histotripsy-mediated cell ablation. AB - This report describes the synthesis of amphiphilic copolymers (ABC-1 and ABC-2) composed of a hydrophilic poly(ethylene glycol) (PEG) block, a central poly(acrylic acid) (PAA) block, and a random copolymer of heptadecafluorodecyl methacrylate (HDFMA) and methyl methacrylate (MMA) forming the hydrophobic block, which are used to form nanodroplets for ultrasound-mediated cell ablation. Specifically, the effect of molecular weight of PEG and P(HDFMA-co-MMA) blocks on polymer's ability to self-assemble around a variable amount (0%, 1%, and 2% v/v) of perfluoropentane (PFP) forming nanodroplets is investigated. The ability of different nanodroplets formulations embedded with a monolayer of red blood cells (RBCs) in tissue-mimicking agarose phantoms to initiate and sustain a bubble cloud in response to ultrasound treatments with different acoustic pressures and the associated ablation of RBCs were also investigated. Results show that ABC-1 polymer composed of a 2 kDa PEG block and a 6.7 kDa P(HDFMA-co-MMA) block better encapsulate the PFP core compared to ABC-2 polymer composed of a 5 kDa PEG block and 11.4 kDa P(HDFMA-co-MMA) block. Further, the ablative capacity indicated by the damage area in the RBCs monolayer increased with the increase in PFP content and reached its maximum with the nanodroplets formulated using ABC-1 polymer and encapsulating 2% v/v PFP. The nanodroplets formulated using ABC-1 polymer and loaded with 2% PFP produced the cavitation cloud and exhibited their ablative effect at an acoustic pressure that is 2.5-fold lower than the acoustic pressure needed to generate the same effect using a histotripsy (ultrasound) pulse alone, which indicates the ability of these nanodroplets to achieve targeted and self limiting fractionation of disease cells while sparing neighboring healthy ones. Results also show that effective nanodroplets maintained their size and concentration upon incubation with bovine serum albumin at 37 degrees C for 24 h, which indicates their stability in physiologic conditions and their promise for in vivo cancer cell ablation. PMID- 25137437 TI - Understanding solvation in the low global warming hydrofluoroolefin HFO-1234ze propellant. AB - Hydrofluoroolefins (HFOs), with zero ozone-depleting effect and very low global warming potential, are considered to be the next-generation high-pressure working fluids. They have industrial relevance in areas including refrigeration and medical aerosols. One major challenge expected in the replacement of existing working fluids with HFOs is the solubility and solvation of additives in such hydrophobic and oleophobic low dielectric semifluorinated solvents. The study of the solvation of chemistries that represent those additives by HFOs is, therefore, of great relevance. In this work, we systematically investigate how the polarity and structure of fragments (the tail, t) that represent those additives affect their binding energy (Eb) with HFO-1234ze (1,1,1,3 tetrafluoropropene) (the solvent, s; Eb(st)). We also compare and contrast those results with those for the working fluids that are most widely used in the industry, the hydrofluoroalkanes (HFAs) HFA-134a and HFA-227. Three main chemistries were investigated: alkanes, ethers, and esters. It was found that HFO 1234ze interacts quite favorably with ethers and esters, as indicated by their Eb(st), while Eb(st) with alkanes was much lower. While ether and ester groups showed little difference in Eb(st), the much lower self-interaction energy between ether tail-tail fragments (Eb(tt)) is expected to result in improved solubility/solvation of those groups in HFO-1234ze when compared with the more polar ester groups. The ratio Eb(st)/Eb(tt) is defined as the enhancement factor (Eenh) and is expected to be a better predictor of solubility/solvation of the tail fragments. The branching of the tail groups upon the addition of pendant CH3 groups did not significantly affect the solvation by the propellant. At low branching density (one CH3 pendant group), it did not affect tail-tail self interaction either. However, at high enough branching (two CH3 groups), steric hindrance caused a significant decrease in Eb(tt) and thus an increase in Eenh, suggesting that branching may be used as a strategy to enhance solvation in HFO propellants. Finally, the solvation behavior of HFO-1234ze was found to be similar to that of HFA-134a, thus suggesting similar considerations may apply for both propellants, when solvation properties are of a concern to the application. PMID- 25137438 TI - Triethylborane-initiated radical chain fluorination: a synthetic method derived from mechanistic insight. AB - We offer a mild, metal-free sp(3) C-H fluorination alternative using Selectfluor and a substoichiometric amount of triethylborane--an established radical initiator in the presence of O2. This radical-chain-based synthetic method is particularly noteworthy as an offspring of the insight gained from a mechanistic study of copper-promoted aliphatic fluorination, constructively turning O2 from an enemy to an ally. Furthermore, BEt3/O2 is a preferred initiator in industrial processes, as it is economical, is low in toxicity, and lends way to easier workup. PMID- 25137436 TI - Effects of nanopillar array diameter and spacing on cancer cell capture and cell behaviors. AB - While substrates with nanopillars (NPs) have emerged as promising platforms for isolation of circulating tumor cells (CTCs), the influence of diameter and spacing of NPs on CTC capture is still unclear. In this paper, CTC-capture yield and cell behaviors have been investigated by using antibody functionalized NPs of various diameters (120-1100 nm) and spacings (35-800 nm). The results show a linear relationship between the cell capture yield and effective contact area of NP substrates where a NP array of small diameter and reasonable spacing is preferred; however, spacing that is too small or too large adversely impairs the capture efficiency and specificity, respectively. In addition, the formation of pseudopodia between captured cells and the substrate is found to be dependent not only on cell adhesion status but also on elution strength and shear direction. These findings provide essential guidance in designing NP substrates for more efficient capture of CTCs and manipulation of cytomorphology in future. PMID- 25137435 TI - Evidence that the C-terminal domain of a type B PutA protein contributes to aldehyde dehydrogenase activity and substrate channeling. AB - Proline utilization A (PutA) is a bifunctional enzyme that catalyzes the oxidation of proline to glutamate. Structures of type A PutAs have revealed the catalytic core consisting of proline dehydrogenase (PRODH) and Delta(1)-pyrroline 5-carboxylate dehydrogenase (P5CDH) modules connected by a substrate-channeling tunnel. Type B PutAs also have a C-terminal domain of unknown function (CTDUF) that is absent in type A PutAs. Small-angle X-ray scattering (SAXS), mutagenesis, and kinetics are used to determine the contributions of this domain to PutA structure and function. The 1127-residue Rhodobacter capsulatus PutA (RcPutA) is used as a representative CTDUF-containing type B PutA. The reaction progress curve for the coupled PRODH-P5CDH activity of RcPutA does not exhibit a time lag, implying a substrate channeling mechanism. RcPutA is monomeric in solution, which is unprecedented for PutAs. SAXS rigid body modeling with target-decoy validation is used to build a model of RcPutA. On the basis of homology to aldehyde dehydrogenases (ALDHs), the CTDUF is predicted to consist of a beta-hairpin fused to a noncatalytic Rossmann fold domain. The predicted tertiary structural interactions of the CTDUF resemble the quaternary structural interactions in the type A PutA dimer interface. The model is tested by mutagenesis of the dimerization hairpin of a type A PutA and the CTDUF hairpin of RcPutA. Similar functional phenotypes are observed in the two sets of variants, supporting the hypothesis that the CTDUF mimics the type A PutA dimer interface. These results suggest annotation of the CTDUF as an ALDH superfamily domain that facilitates P5CDH activity and substrate channeling by stabilizing the aldehyde-binding site and sealing the substrate-channeling tunnel from the bulk medium. PMID- 25137439 TI - Fabrication of Si/ZnS radial nanowire heterojunction arrays for white light emitting devices on Si substrates. AB - Well-separated Si/ZnS radial nanowire heterojunction-based light-emitting devices have been fabricated on large-area substrates by depositing n-ZnS film on p-type nanoporous Si nanowire templates. Vertically oriented porous Si nanowires on p-Si substrates have been grown by metal-assisted chemical etching catalyzed using Au nanoparticles. Isolated Si nanowires with needle-shaped arrays have been made by KOH treatment before ZnS deposition. Electrically driven efficient white light emission from radial heterojunction arrays has been achieved under a low forward bias condition. The observed white light emission is attributed to blue and green emission from the defect-related radiative transition of ZnS and Si/ZnS interface, respectively, while the red arises from the porous surface of the Si nanowire core. The observed white light emission from the Si/ZnS nanowire heterojunction could open up the new possibility to integrate Si-based optical sources on a large scale. PMID- 25137440 TI - A simple validated RP-HPLC bioanalytical method for the quantitative determination of a novel valproic acid arylamide derivative in rat hepatic microsomes. AB - A simple and specific bioanalytical method based on reversed-phase high performance liquid chromatography (RP-HPLC) coupled with ultraviolet detection was developed and validated for the determination of a novel valproic acid arylamide, N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) in rat hepatic microsomes (a subcellular fraction containing phase I enzymes, especially cytochrome P450). The chromatographic separation was achieved using a reversed phase Zorbax SB-C18 column and a mobile phase of acetic acid in water (0.2% v/v) and acetonitrile (40:60 v/v) with a flow rate of 0.5 mL/min. The calibration curve was linear over the range of 882-7060 ng/mL (r(2) = 0.9987), and the lower limit of quantification and the lower limit of determination were found to be 882 and 127.99 ng/mL, respectively. The method was validated with excellent sensitivity, and intra-day accuracy and precision varied from 93.79 to 93.12%, and from 2.12 to 4.36%, respectively. The inter-day accuracy and precision ranged from 93.29 to 97.30% and from 0.68 to 3.60%, respectively. The recovery of HO AAVPA was measured between 91.36 and 97.98%. The assay was successfully applied to the analysis of kinetic metabolism and pharmacokinetic parameters in vitro by a substrate depletion approach. PMID- 25137441 TI - Syntheses of two vanadium oxide-fluoride materials that differ in phase matchability. AB - The syntheses of two noncentrosymmetric (NCS) vanadium oxide-fluoride compounds that originate from the same synthetic reagent concentrations are presented. Hydrothermal and low-temperature syntheses allow the isolation of metastable products that may form new phases (or decompose) upon heating and allow creation of chemically similar but structurally different materials. NCS materials synthesis has been a long-standing goal in inorganic chemistry: in this article, we compare two chemically similar NCS inorganic materials, NaVOF(4)(H(2)O) (I) and NaVO(2-x)F(2+x) (II; x = 1/3). These materials originate from the same, identical reagent mixtures but are synthesized at different temperatures: 100 degrees C and 150 degrees C, respectively. Compound I crystallizes in Pna2(1): a = 9.9595(4) A, b = 9.4423(3) A, and c = 4.8186(2) A. Compound II crystallizes in P2(1): a = 6.3742(3) A, b = 3.5963(2) A, c = 14.3641(7) A, and beta = 110.787(3) degrees . Both materials display second-harmonic-generation activity; however, compound I is type 1 non-phase-matchable, whereas compound II is type 1 phase matchable. PMID- 25137442 TI - Bioarcheology has a "health" problem: conceptualizing "stress" and "health" in bioarcheological research. AB - This article provides a critical historical overview of the stress concept in bioarcheological research and critically evaluates the term "health" in reference to skeletal samples. Stress has a considerable history in 20th century physiological research, and the term has reached a critical capacity of meaning. Stress was operationalized around a series of generalized physiological responses that were associated with a deviation from homeostasis. The term was incorporated into anthropological research during the mid-20th century, and further defined in bioarcheological context around a series of skeletal indicators of physiological disruption and disease. Emphases on stress became a predominate area of research in bioarcheology, and eventually, many studies utilized the terms "health" and "stress" interchangeably as part of a broader, problem-oriented approach to evaluating prehistoric population dynamics. Use of the term "health" in relation to skeletal samples is associated with the intellectual history of bioarcheological research, specifically influences from cultural ecology and processualist archeology and remains problematic for two reasons. First, health represents a comprehensive state of well-being that includes physiological status and individual perception, factors that cannot be readily observed in skeletal samples. Second, the categorization of populations into relative levels of health represents a typological approach, however unintentional. This article advocates for the integration of methodological and theoretical advances from human biology and primatology, while simultaneously incorporating the theoretical constructs associated with social epidemiology into bioarcheological research. Such an approach will significantly increase the applicability of bioarcheological findings to anthropological and evolutionary research, and help realize the goal of a truly relevant bioarcheological paradigm. PMID- 25137443 TI - Importance of sample form and surface temperature for analysis by ambient plasma mass spectrometry (PADI). AB - Many different types of samples have been analyzed in the literature using plasma based ambient mass spectrometry sources; however, comprehensive studies of the important parameters for analysis are only just beginning. Here, we investigate the effect of the sample form and surface temperature on the signal intensities in plasma-assisted desorption ionization (PADI). The form of the sample is very important, with powders of all volatilities effectively analyzed. However, for the analysis of thin films at room temperature and using a low plasma power, a vapor pressure of greater than 10(-4) Pa is required to achieve a sufficiently good quality spectrum. Using thermal desorption, we are able to increase the signal intensity of less volatile materials with vapor pressures less than 10(-4) Pa, in thin film form, by between 4 and 7 orders of magnitude. This is achieved by increasing the temperature of the sample up to a maximum of 200 degrees C. Thermal desorption can also increase the signal intensity for the analysis of powders. PMID- 25137444 TI - Best practice or last resort? Employing graduate teaching assistants as clinical instructors. AB - Many institutions need to employ GTAs, and students need the teaching experience that working as a GTA offers. Some recommendations to support a positive outcome are as follows: (1) GTAs should not make up a significantly large percentage of the total clinical faculty employed. Yet within reasonable limits, employ GTAs, wherever possible; (2) evaluate GTAs' performance on an ongoing as well as summative basis to be sure that they are meeting expectations set for providing instruction; and (3) hire new faculty members who worked previously as a GTA or in similar roles to ensure faculty succession with educators who are clinical experts. PMID- 25137445 TI - Use of multiuser, high-fidelity virtual simulation to teach leadership styles to nursing students. PMID- 25137446 TI - Integrating an academic electronic health record in a nursing program: creating a sense of urgency and sustaining change. PMID- 25137447 TI - Clinical coordinator role in a nursing program: challenges and rewards, perils and pitfalls. PMID- 25137448 TI - Interprofessional education competencies. PMID- 25137449 TI - Barcode training innovation. PMID- 25137450 TI - Podcasting in undergraduate nursing programs. AB - Little information is available regarding the value of podcasting in nursing education. This mixed-methods study described nursing students' (n=101) perceptions of podcasted materials, the benefits of podcasting, and when and where students used podcasted materials. Students (86%) believed podcasts enriched their learning, and 95% reported podcasts as valuable tools in the learning environment. Most students (94%) would recommend podcasting in other courses and accessed podcast materials 3 times per week. More than half of the students (55%) accessed podcast materials in multiple places (ie, in the car, in the home, and at school). PMID- 25137451 TI - Investigating the effects of solvent on the ultrafast dynamics of a photoreversible ruthenium sulfoxide complex. AB - The photochromic complex [Ru(bpy)2(pySO)](2+) [pySO is 2 (isopropylsulfinylmethyl)pyridine] undergoes wavelength specific, photoreversible S -> O and O -> S linkage isomerizations. Irradiation of the ground state S bonded complex with blue light produces the O-bonded isomer, while irradiation of the O-bonded isomer with green light produces the S-bonded isomer. Furthermore, isomerization time constants are solvent-dependent. Ultrafast transient absorption spectroscopy has been employed to investigate the relaxation processes that lead to S -> O isomerization in 1,2-dichloroethane, propylene carbonate, and ethylene glycol. The isomerization is most rapid in 1,2-dichloroethane and slowest in ethylene glycol. Photochemical reversion of the O-bonded isomer in propylene carbonate has further been investigated and indicates similar relaxation or isomerization kinetics, though the excited states that lead to isomerization are distinct between the S- and O-bonded isomers. PMID- 25137452 TI - A primer on TCR signaling. PMID- 25137453 TI - Integrative biology of T cell activation. AB - The activation of T cells mediated by the T cell antigen receptor (TCR) requires the interaction of dozens of proteins, and its malfunction has pathological consequences. Our major focus is on new developments in the systems-level understanding of the TCR signal-transduction network. To make sense of the formidable complexity of this network, we argue that 'fine-grained' methods are needed to assess the relationships among a few components that interact on a nanometric scale, and those should be integrated with high-throughput '-omic' approaches that simultaneously capture large numbers of parameters. We illustrate the utility of this integrative approach with the transmembrane signaling protein Lat, which is a key signaling hub of the TCR signal-transduction network, as a connecting thread. PMID- 25137454 TI - Insights into the initiation of TCR signaling. AB - The initiation of T cell antigen receptor signaling is a key step that can result in T cell activation and the orchestration of an adaptive immune response. Early events in T cell receptor signaling can distinguish between agonist and endogenous ligands with exquisite selectivity, and show extraordinary sensitivity to minute numbers of agonists in a sea of endogenous ligands. We review our current knowledge of models and crucial molecules that aim to provide a mechanistic explanation for these observations. Building on current understanding and a discussion of unresolved issues, we propose a molecular model for initiation of T cell receptor signaling that may serve as a useful guide for future studies. PMID- 25137463 TI - Francois Kourilsky 1934-2014. PMID- 25137455 TI - Serine-threonine kinases in TCR signaling. AB - T lymphocyte proliferation and differentiation are controlled by signaling pathways initiated by the T cell antigen receptor. Here we explore how key serine threonine kinases and their substrates mediate T cell signaling and coordinate T cell metabolism to meet the metabolic demands of participating in an immune response. PMID- 25137456 TI - The self-obsession of T cells: how TCR signaling thresholds affect fate 'decisions' and effector function. AB - Self-reactivity was once seen as a potential characteristic of T cells that was eliminated by clonal selection to protect the host from autoimmune pathology. It is now understood that the T cell repertoire is in fact broadly self-reactive, even self-centered. The strength with which a T cell reacts to self ligands and the environmental context in which this reaction occurs influence almost every aspect of T cell biology, from development to differentiation to effector function. Here we highlight recent advances and discoveries that relate to T cell self-reactivity, with a particular emphasis on T cell antigen receptor (TCR) signaling thresholds. PMID- 25137464 TI - Breaking barriers: a GPCR triggers immunity in nematodes. PMID- 25137465 TI - c-Myc and AP4: a relay team for metabolic reprogramming of CD8+ T cells. PMID- 25137474 TI - Retraction: Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. PMID- 25137466 TI - RNA exosomes keep endogenous RNA under the radar. PMID- 25137478 TI - Small-molecule suppression of beta-lactam resistance in multidrug-resistant gram negative pathogens. AB - Recent efforts toward combating antibiotic resistance in bacteria have focused on Gram-positive bacteria; however, multidrug-resistant Gram-negative bacteria pose a significant risk to public health. An orthogonal approach to the development of new antibiotics is to develop adjuvant compounds that enhance the susceptibility of drug-resistant strains of bacteria to currently approved antibiotics. This paper describes the synthesis and biological activity of a library of aryl amide 2-aminoimidazoles based on a lead structure from an initial screen. A small molecule was identified from this library that is capable of lowering the minimum inhibitory concentration of beta-lactam antibiotics by up to 64-fold. PMID- 25137479 TI - High-density, stretchable, all-solid-state microsupercapacitor arrays. AB - We report on the successful fabrication of stretchable microsupercapacitor (MSC) arrays on a deformable polymer substrate that exhibits high electrochemical performance even under mechanical deformation such as bending, twisting, and uniaxial strain of up to 40%. We designed the deformable substrate to minimize the strain on MSCs by adopting a heterogeneous structure consisting of stiff PDMS islands (on which MSCs are attached) and a soft thin film (mixture of Ecoflex and PDMS) between neighboring PDMS islands. Finite element method analysis of strain distribution showed that an almost negligible strain of 0.47% existed on the PDMS islands but a concentrated strain of 107% was present on the soft thin film area under a uniaxial strain of 40%. The use of an embedded interconnection of the liquid metal Galinstan helped simplify the fabrication and provided mechanical stability under deformation. Furthermore, double-sided integration of MSCs increased the capacitance to twice that of MSCs on a conventional planar deformable substrate. In this study, planar-type MSCs with layer-by-layer assembled hybrid thin film electrodes of MWNT/Mn3O4 and PVA-H3PO4 electrolyte were fabricated; when they are integrated into a circuit, these MSCs increase the output voltage beyond the potential of the electrolyte used. Therefore, various LEDs that require high voltages can be operated under a high uniaxial strain of 40% without any decrease in their brightness. The results obtained in this study demonstrate the high potential of our stretchable MSC arrays for their application as embedded stretchable energy storage devices in bioimplantable and future wearable nanoelectronics. PMID- 25137480 TI - Microgel-like aggregates of isotactic and atactic poly(methacrylic acid) chains in aqueous alkali chloride solutions as evidenced by light scattering. AB - A comparative light-scattering study of isotactic and atactic poly(methacrylic acid), iPMA and aPMA, respectively, in aqueous solutions with added alkali chlorides, XCl (X = Li, Na, Cs), at 25 degrees C and XCl concentration of 0.1 mol L(-1), demonstrates that both PMA isomers are strongly associated at low degrees of neutralization, alphaN (= 0 for aPMA and 0.25 for iPMA), in the presence of all XCls. The shape parameter rho and the scattering functions suggest that aggregates have the characteristics of microgel particles, with a dense core surrounded by a less dense shell. The extent of aggregation depends on the stereoregular structure of the polymer and on the type of the added cation. Li(+) and Na(+) ions support aggregation better than Cs(+) ions. Besides, iPMA chains are more strongly aggregated than aPMA chains and form particles with a denser core. A model of the aggregation process is suggested for iPMA. At high alphaN, a slow diffusive process (so-called extraordinary or anomalous mode in diffusion of polyelectrolytes), arising from electrostatic interactions between charged chains, is observed for both PMAs. Results suggest that under the same experimental conditions iPMA is effectively more charged than aPMA. The role of ions in the slow-mode phenomenon is less pronounced than in aggregation. PMID- 25137481 TI - Response to "power in the study of mortality and necrotizing soft tissue infections". PMID- 25137482 TI - Resurfaced shape complementary proteins that selectively bind the oncoprotein gankyrin. AB - Increased cellular levels of protein-protein interactions involving the ankyrin repeat oncoprotein gankyrin are directly linked to aberrant cellular events and numerous cancers. Inhibition of these protein-protein interactions is thus an attractive therapeutic strategy. However, the relatively featureless topology of gankyrin's putative binding face and large surface areas involved in gankyrin dependent protein-protein interactions present a dramatic challenge to small molecule discovery. The size, high folding energies, and well-defined surfaces present in many proteins overcome some of the challenges faced by small molecule discovery. We used split-superpositive Green Fluorescent Protein (split-spGFP) reassembly to screen a 5*10(9) library of resurfaced proteins that are shape complementary to the putative binding face of gankyrin and identified mutants that potently and selectively bind this oncoprotein in vitro and in living cells. Collectively, our findings represent the first synthetic proteins that bind gankyrin and may represent a general strategy for developing protein basic research tools and drug leads that bind disease-relevant ankyrin repeats. PMID- 25137483 TI - Carbohydrate-to-carbohydrate interactions between alpha2,3-linked sialic acids on alpha2 integrin subunits and asialo-GM1 underlie the bone metastatic behaviour of LNCAP-derivative C4-2B prostate cancer cells. AB - Complex interplays among proteins, lipids and carbohydrates can alter the phenotype and are suggested to have a crucial role in tumour metastasis. Our previous studies indicated that a complex of the GSLs (glycosphingolipids), AsGM1 (asialo-GM1), which lacks alpha2,3-linked sialic acid, and alpha2beta1 integrin receptors is responsible for the metastatic behaviour of C4-2B prostate cancer cells. Herein, we identified and addressed the functional significance of changes in sialylation during prostate cancer progression. We observed an increase in alpha2,3-linked sialic acid residues on alpha2 subunits of alpha2beta1 integrin receptors, correlating with increased gene expression of alpha2,3-STs (sialyltransferases), particularly ST3GAL3. Cell surface alpha2,3-sialylation of alpha2 subunits was required for the integrin alpha2beta1-dependent cell adhesion to collagen type I and the same alpha2,3-linked sialic acid residues on the integrin receptor were responsible for the interaction with the carbohydrate moiety of AsGM1, explaining the complex formation between AsGM1 and alpha2beta1 integrin receptors. These results provide novel insights into the role of sialic acids in the organization and function of important membrane components in invasion and metastatic processes. PMID- 25137484 TI - Variability and reliability of diurnal cortisol in younger and older adults: implications for design decisions. AB - The extant research is inconclusive regarding the best sampling methods to construct reliable measures of between-person differences in derived parameters of diurnal cortisol, and no study provides such recommendations for detecting within-person changes. These studies determined how many days of sampling are necessary to assess between-person differences and within-person changes over multiple occasions in diurnal mean, diurnal slope, and area under the curve (AUC). Generalizability and decision analyses were conducted on diurnal salivary cortisol data from two separate longitudinal studies, one with younger adults (N=124) and one with older adults (N=148). In both studies, results indicated that 3 days of data collection provided the minimal level of reliability in mean cortisol to detect between-person differences; 4-8 days were necessary to reliably assess AUC, and 10 days for cortisol slope. Similarly, in order to reliably characterize within-person changes across occasions, at least 3 days of data collection were needed for mean cortisol and AUC and 5-8 days for slope. Results also indicated that only two samples per day, taken morning and evening, could faithfully reproduce the diurnal slope calculated from 3 or 4 samples (r=.97-.99). Instead of having participants provide many samples per day over the course of a few days, we recommend collecting fewer samples per day over more days. PMID- 25137486 TI - Staffing of healthcare workers and patient mortality: randomized trials needed. AB - In a Perspective accompanying a study by Benjamin Bray and colleagues, Meeta Kerlin discusses the evidence that physician and nurse workforces are associated with patient mortality, why clearer guidelines for appropriate workforce size are not available, and the next steps needed to address the knowledge gaps. Please see later in the article for the Editors' Summary. PMID- 25137485 TI - Stability and predictors of change in salivary cortisol measures over six years: MESA. AB - A major challenge in characterizing features of the daily cortisol curve is variability in features over time. Few studies have examined the stability of daily features of the cortisol curve over long periods or the predictors of long term changes. Repeated salivary cortisol measures on 580 adults from the MESA Stress study were used to examine the stability of various features of the daily cortisol curve (wakeup value, the cortisol awakening response (CAR), the early and late decline slope and the area under the curve (AUC)), over short periods (several days) and long periods (approximately 6-years) and to investigate the association of demographic factors with the changes. Intraclass correlation coefficients (ICCs) were used to estimate the short and long term stability. Piecewise linear mixed models were used to assess factors associated with changes in features over time. For most features, short term stability (ICCs: 0.17-0.74) was higher than long term stability (ICCs: 0.05-0.42), and long term stability was highest when several days were averaged for each time point. The decline over the day showed the highest long term stability: when several days for each wave were averaged the stability of the daily decline slope across 6 years was similar (or higher) than the stability across short periods. AUC had high stability over short periods (ICCs: 0.65-0.74) but much lower stability across long periods (ICC: 0.05). All features of daily cortisol curve investigated changed significantly over the approximately 6 year follow-up period. The wakeup cortisol became higher; the CAR became smaller; both the early and late decline became flatter; and the AUC became larger. Hispanics experienced significantly larger increases in the wakeup value; and African-Americans and Hispanics showed less flattening over time of the early decline slope than Non-Hispanic Whites. Our findings have implications for characterization of features in studies linking cortisol to health outcomes. The presence of variability over time suggests opportunities for future investigation of the predictors of changes over time as well as the links between these changes and health outcomes. PMID- 25137488 TI - Boronate affinity nanoparticles for nucleoside separation. AB - Boronate affinity systems have been recently used for the specific isolation of cis-diol group carrying biomolecules such as glycoproteins, nucleosides, carbohydrates. Nanosized materials have been extremely used for the biotechnological purposes due to their unique properties and their high surface areas. The objective of this presented work was to develop a new boronate affinity system for the nucleoside adsorption. For this purpose, poly(HEMA) nanoparticles were synthesized by using surfactant free emulsion polymerization technique and then functionalized with phenylboronic acid. Synthesized nanoparticles were characterized with FTIR, SEM, and Zeta size analysis. Nucleic acid adsorption experiments were repeated for different medium pH values, for various nucleosides concentrations, for different temperatures and ionic strengths, in order to determine the optimum adsorption conditions. In the light of these studies, it can be concluded that this boronate ligand carrying nanoparticles were very valuable for the separation of nucleosides. PMID- 25137490 TI - Geo-engineering in lakes: a crisis of confidence? PMID- 25137489 TI - Advances in preparation and characterization of chitosan nanoparticles for therapeutics. AB - CONTEXT: Polymers have been largely explored for the preparation of nanoparticles due to ease of preparation and modification, large gene/drug loading capacity, and biocompatibility. Various methods have been adapted for the preparation and characterization of chitosan nanoparticles. OBJECTIVE: Focus on the different methods of preparation and characterization of chitosan nanoparticles. METHODS: Detailed literature survey has been done for the studies reporting various methods of preparation and characterization of chitosan nanoparticles. RESULTS AND CONCLUSION: Published database suggests of several methods which have been developed for the preparation and characterization of chitosan nanoparticles as per the application. PMID- 25137487 TI - Illuminating breast cancer invasion: diverse roles for cell-cell interactions. AB - Metastasis begins when tumors invade into surrounding tissues. In breast cancer, the study of cell interactions has provided fundamental insights into this complex process. Powerful intravital and 3D organoid culture systems have emerged that enable biologists to model the complexity of cell interactions during cancer invasion in real-time. Recent studies utilizing these techniques reveal distinct mechanisms through which multiple cancer cell and stromal cell subpopulations interact, including paracrine signaling, direct cell-cell adhesion, and remodeling of the extracellular matrix. Three cell interaction mechanisms have emerged to explain how breast tumors become invasive: epithelial-mesenchymal transition, collective invasion, and the macrophage-tumor cell feedback loop. Future work is needed to distinguish whether these mechanisms are mutually exclusive or whether they cooperate to drive metastasis. PMID- 25137491 TI - Recent developments in biological activities of chalcones: a mini review. AB - Chalcones represent key structural motif in the plethora of biologically active molecules including synthetic and natural products. Synthetic manipulations of chalcones or their isolation from natural sources are being investigated worldwide for the development of more potent and efficient drugs for the treatment of several dreadful diseases such as cancer, diabetes, HIV, tuberculosis, malaria etc. Over the past few years, a large volume of research papers and review articles highlighting the significance of chalcone derivatives has been compiled in the literature. The present review article focuses on the recent developments (2010-2014) on various pharmacological and medicinal aspects of chalcones and their analogues. PMID- 25137492 TI - Apoptosis and necrosis in the circumventricular organs after experimental subarachnoid hemorrhage as detected with annexin V and caspase 3 immunostaining. AB - OBJECTIVES: The circumventricular organs (CVOs) are essential for most autonomic and endocrine functions. Trauma and bleeding can affect their function. The aim of this study was to investigate apoptosis and necrosis in CVOs in the early period after experimental subarachnoid hemorrhage (SAH) in rats, using annexin V affinity and caspase 3 immunostaining. METHODS: Three experimental groups were used: Days 1 and 2 after SAH, and a control group, seven Wistar albino rats each. Subarachnoid hemorrhage was accomplished by transclival basilar artery puncture. Rats were perfused with 0.9% NaCl and 0.1M phosphate buffer pH 7.4 until heart stoppage. Apoptosis and necrosis in CVOs were measured by flow cytometry with annexin V staining, and by caspase 3 immunostaining. RESULTS: Apoptosis in the organum vasculosum lamina terminalis (OVLT), median eminence (ME), and area postrema (AP) was significantly higher in the Day 1 group than in the control group. Apoptosis in the subfornicial organ (SFO), OVLT, ME, and AP was significantly higher in the Day 2 group than in the control group. There were significant differences between the Day 1 and Day 2 groups, except for AP. Necrosis in SFO and OVLT was significantly higher in the Day 2 group than in the Day 1 or control groups, whereas necrosis in the ME and AP did not differ between the three groups. Caspase 3-positive cell density was more intense in the Day 2 group than in the Day 1 and control groups. DISCUSSION: Prevention of apoptosis may potentially improve impaired functions of CVOs after SAH. PMID- 25137494 TI - Multilayered modeling of particulate matter removal by a growing forest over time, from plant surface deposition to washoff via rainfall. AB - Airborne fine particulate matter (PM) is responsible for the most severe health effects induced by air pollution in Europe. Vegetation, and forests in particular, can play a role in mitigating this pollution since they have a large surface area to filter PM out of the air. Many studies have solely focused on dry deposition of PM onto the tree surface, but deposited PM can be resuspended to the air or may be washed off by precipitation dripping from the plants to the soil. It is only the latter process that represents a net-removal from the atmosphere. To quantify this removal all these processes should be accounted for, which is the case in our modeling framework. Practically, a multilayered PM removal model for forest canopies is developed. In addition, the framework has been integrated into an existing forest growth model in order to account for changes in PM removal efficiency during forest growth. A case study was performed on a Scots pine stand in Belgium (Europe), resulting for 2010 in a dry deposition of 31 kg PM2.5 (PM < 2.5 MUm) ha(-1) yr(-1) from which 76% was resuspended and 24% washed off. For different future emission reduction scenarios from 2010 to 2030, with altering PM2.5 air concentration, the avoided health costs due to PM2.5 removal was estimated to range from 915 to 1075 euro ha(-1) yr(-1). The presented model could even be used to predict nutrient input via particulate matter though further research is needed to improve and better validate the model. PMID- 25137495 TI - Tears of the rotator cuff. Causes--diagnosis--treatment. AB - Rotator cuff ruptures are the most common degenerative tendon injury and occur mainly in older patients as multifactorial disorders manifesting the main symptoms of pain and restricted range of motion. Thorough clinical examination of the shoulder includes testing the function of the rotator cuff and leads to a tentative clinical diagnosis that is the prerequisite for diagnostic imaging procedures. Sonography of the shoulder gives rapid access to a very good sensitive overview of the rotator cuff. Conventional radiological imaging permits differential diagnosis since a reduced acromiohumeral interval is understood as a direct sign of rotator cuff rupture. The gold standard in imaging diagnostics is MRI because it not only delivers images of rotator cuff defects, but also permits interpretation of degenerative changes in the musculature. Significant pain relief can be achieved by conservative therapy such as analgesia, manual therapy and physiotherapeutic exercises and leads to improvements in the active range of motion. Persistent pain or progressive pain during conservative therapy are indications for surgical intervention. Arthroscopy-assisted treatment is tissue friendlier than open surgery and is today considered the standard for surgical treatment of rotator cuff rupture because of higher patient acceptance. Recent studies report that surgical rotator cuff repair leads to significant improvement in function, pain relief, and greater patient satisfaction. The principles of postoperative care after surgical rotator cuff repair are immobilization and gradual loading with passive and active exercises. PMID- 25137493 TI - Vitamin D status and predictors of serum 25-hydroxyvitamin D concentrations in Western Australian adolescents. AB - Despite the importance of skeletal growth during adolescence, there is limited research reporting vitamin D status and its predictors in adolescents. Using prospective data from the Western Australian Pregnancy Cohort (Raine) Study, we investigated vitamin D status and predictors of serum 25-hydroxyvitamin D (25(OH)D) concentrations in adolescents. Serum 25(OH)D concentrations were measured in the same participants at 14 and 17 years (n 1045 at both time points). The percentage of adolescents with serum 25(OH)D concentrations < 50, 50 74.9 and >= 75 nmol/l was reported year-round and by month of blood collection. We examined the predictors of serum 25(OH)D concentrations, including sex, race, month of blood collection, physical activity, BMI, family income, and Ca and vitamin D intakes (n 919 at 14 years; n 570 at 17 years), using a general linear mixed model. At 14 years, 31 % of adolescents had serum 25(OH)D concentrations between 50 and 74.9 nmol/l and a further 4 % had concentrations < 50 nmol/l. At 17 years, 40 % of adolescents had serum 25(OH)D concentrations between 50 and 74.9 nmol/l and 12 % had concentrations < 50 nmol/l. Caucasian ethnicity, being sampled at the end of summer, exercising more, having a lower BMI, a higher Ca intake and a higher family income were significantly associated with higher serum 25(OH)D concentrations. The proportion of adolescents with serum 25(OH)D concentrations < 50 nmol/l was low in this Western Australian cohort. There is a need for international consensus on defining adequate vitamin D status in order to determine whether strategies to increase vitamin D status in adolescents are warranted. PMID- 25137496 TI - Biomechanical and biological aspects of defect treatment in fractures using helical plates. AB - The clinical case of figure 1 through figure 11 shows a series of impressive failures of plate fixation. The plates were repeatedly applied bridging a comminuted bone segment in a heavy patient. The biomechanical analysis elaborates why this happened and proposes an unconventional procedure to prevent this failure with a minimally invasive procedure. A plate bridging an open gap or a defect in a long bone diaphysis is exposed to full functional load. According to clinical observations such plate application often fails even without external load such as weight bearing. The plate risks to break through fatigue when exposed during a long time to cyclic loading. This type of failure has been observed even with broad plates as well in femoral as in tibiae. The first option to avoid such failure consists in protecting the plate by installing load sharing between plate and either bone or an additional implant. This reduces the load carried by the plate to a safe level. Load sharing with bone may be installed at surgery by establishing solid mechanical bridge between the two main fragments of the fractured bone. The optimal load sharing relies on a solid compressed contact between the main fragments. It can be established because the bone is able to take a large load which results in optimal protection of the plate. In the case of an extended comminuted bone segment it may be very difficult, traumatizing and inefficient to reconstruct the bone. In the present case it was impossible to establish load sharing through the bone. The second option protecting the plate is provided by callus bridging of the gap or defect. The formation of a solid callus bridge takes time but the fatigue failure of the plate also takes time. Therefore, the callus bridge may prevent a late fatigue failure. The surgeon may select one of several options: - Replacing the lack of bone support using a second plate which immediately alleviates plate loading. The drawback of application of a second conventional plate is the extent of surgical trauma at the critical site of healing. - Shingling and/or applying an autologous cancellous bone graft: This procedure provides initially no relevant load sharing but will do so after a couple of weeks. The mechanical coupling of the comparably soft graft and the main fracture fragments presents little problems. Applying a cortical bone graft: Such a graft does provide initial only small load sharing and does a less good job inducing callus than a cancellous graft. Furthermore, the coupling by callus between a somewhat rigid bone graft and the mobile main fracture fragments requires a solid maintained contact. If the cortical graft is fixed using implants with small contact area to the graft such as screws or cerclage loops, the local stress may be critical and the graft may break. When the cortical graft is fixed with cerclage wires the procedure must take into account the limited strength of the individual cerclage. Therefore multiple and well-spaced cerclages are required and may lead to success especially if an intramedullary component of the implant contributes to protection (6). The degree of unloading depends apparently on the stiffness of the material of the protecting splint. Though, more important is the effect of the dimensions of the splint. While titanium as a material is about 50% less stiff than steel, the thickness of the implant changes the stiffness with the third power. That is doubling the thickness results in eightfold increased stiffness. When considering the unloading by application of a second plate the leverage of the second plate plays an important role. The larger the distance between the axis of bending and the second implant the larger the protecting effect. The helical plate (2, 3, 7) as introduced by A.A.D. Fernandez offers biological and mechanical advantages. It can be applied without touching the fracture site maintaining the critical biology intact and provides mechanically efficient unloading. Its application is fairly simple: The helical plate is modified conventional long and small plate that is twisted between its ends about 90 degrees. The twist is applied using "bending irons" (4, 5, 8) whereby the force required is small and the exact degree of twist is not critical. Therefore the twist is applicable operating bending irons by hand. Assuming a situation where a plate bridging a defect or non-union has failed the broken plate is replaced by a similar implant: At the distal end of the bone fracture and opposite to the surgical approach a small incision allows to slide in the helical plate in such a way that proximally the plate ends on the same side of the limb as the replaced plate. Ideally the two plate ends meet and the application of the helical plate does not ask for an additional surgical exposure at this location. Otherwise a small minimally invasive exposure is required. The helical plate is then fixed to the main bone fragments using a couple of locked screws. The following case demonstrates the use and efficiency of the helical plate saving a situation where multiple attempts using conventional plates had failed. The successful final treatment of this case was performed by A. A. D. Fernandez. PMID- 25137497 TI - Determining the risk of falling in elderly patients undergoing hip fracture surgery. AB - PURPOSE OF THE STUDY This study examines the risk of falling in elderly patients who underwent hip fracture surgery in the orthopaedic clinic during the postoperative period. MATERIALS AND METHODS This study was a cross-sectional study. The study sample consisted of 71 elderly patients aged more than 65 years undergoing hip fracture surgery. A questionnaire, the Tinetti balance test and the mini-mental state examination (MMSE) were used. RESULTS The analyses included 71 elderly patients with a mean age of 78.45 years. All patients had been hospitalized for hip fracture due to falling, and 29.6% had a history of falling in the one year prior to hospitalization. The mean MMSE score was 18.37 +/- 6.54 and the mean Tinetti score was 11.10 +/- 6.66. CONCLUSION We found that as the mean age of the elderly patients increased, the risk of falling also increased and the MMSE scores deteriorate and that the elderly patients living alone were at a greater risk of falling and had worse cognitive function, that those with a history of falling before hospitalization were at a greater risk of falling again and that the risk of falling increased as cognitive function declined. Key words:elderly, falling, hip fracture, risk of falling. PMID- 25137498 TI - [The effect of central anatomical single-bundle versus anatomical double-bundle reconstruction of the anterior cruciate ligament on knee stability. a clinical study]. AB - PURPOSE OF THE STUDY A comparison of the efficacy of central anatomical single bundle (CASB) reconstruction with that of double-bundle (DB) repair of the anterior cruciate ligament (ACL) in relation to knee stability in anteroposterior translation (APT), internal rotation (IR) and external rotation (ER) of the joint. MATERIAL AND METHODS A total of 40 patients were evaluated; 20 had ACL reconstruction by the CASB technique using hamstrings and 20 underwent DB repair surgery. The average age was 31.3 years, and the group included 22 men and 18 women with 19 right and 21 left knees. The KT-1000 test was used to assess the amount of APT in the knee and rotational deviations were measured by the Rolimeter. In the DB patients, measurements were performed before surgery (on joints with ACL injury), then after reconstruction of the anteromedial (AM) or the posterolateral (PL) bundle and subsequently after repair of both ACL bundles. The CASB patients were assessed before and after graft insertion. RESULTS The average APT value was 18.5 mm for the pre-operative knees and it fell to 8.9 mm after AM bundle reconstruction. However, when the PL bundle was inserted in the first place, the average APT value was 13.1 mm only. The average values recorded after the DB and CASB reconstructions were 6.1 mm and 9.1 mm, respectively. The average IR range of motion in the pre-operative joints was 18.6 degrees. After AM bundle reconstruction it was 13.9 degrees and after PL bundle repair it was 15.3 degrees. In DB reconstruction the average IR value achieved 10.4 degrees, and in CASB repair surgery it was 13.7 degrees. The average ER range of motion in the pre-operative joints was 17.8 degrees. After AM bundle reconstruction it was 14.5 degrees and after PL bundle repair it was 14.9 degrees. In DB reconstruction the average ER value achieved 11.4 degrees, and in CASB repair surgery it was 14.5 degrees. DISCUSSION Rotational stability of the knee after ACL reconstruction is one of the most important factors in restoring physiological kinematics of the joint after ACL injury. Since there are not many studies comparing knee rotational stability after CASB with that after DB reconstructions, the results presented here may contribute to selecting the optimal method of ACL reconstruction. CONCLUSIONS The results show that, in ACL reconstruction, the DB technique provides better stability to the knee, in both APT and rotation, than the CASB method. The latter has the same effect on knee stability as the presence of the AM bundle alone. When the PL bundle is added, knee stability, in both APT and internal/external rotation, is increased in comparison with central single bundle ACL repair. Key words:anterior cruciate ligament, navigation, central anatomical single-bundle reconstruction, double-bundle reconstruction. PMID- 25137499 TI - [The angular profile of a cage has no influence on segmental alignment after anterior cervical stand-alone interbody fusion]. AB - PURPOSE OF THE STUDY: The original aim of this prospective semi-randomised study was to determine associations between segmental sagittal alignment after Anterior Cervical Discectomy and Fusion (ACDF) and subjective and clinical results. Two types of cages, cage P with parallel end-plates and cage A with 5-degree angulations, were used in the patients treated for degenerative conditions. MATERIAL AND METHODS: A total of 94 consecutive patients, 56 treated by single level ACDF and 38 undergoing a two-level procedure, completed 8 years of follow up. The patients in equally-sized A and P subgroups were examined at 6 weeks and 1, 2 and 8 years after surgery. The follow-up included X-ray in a neutral lateral position, a questionnaire assessing pain in neck and shoulder regions and JOA scores. The results including the cumulative incidence of surgical procedures indicated for adjacent segment diseases were statistically evaluated. RESULTS: An average increase in the lordotic angle at 6 weeks after surgery was 2.32 degrees for the implant P and 2.02 degrees for the implant A subgroup. During 8 years of follow-up the average values decreased to 1.51 degrees and 1.36 degrees , respectively. The proportion of patients with no or minimal neck and shoulder pain decreased, in subgroup P, from the initial 85% at 6 weeks to 59% at 8 years after the surgery and, in subgroup A, from 89% to 40 %. The average JOA score of 16 at 6 weeks in both subgroups, at 8 years, had a value of 15.9 in subgroup P and 16.0 in subgroup A. The cumulative incidence of surgery for adjacent segment disease 8 years was 8.3% for subgroup P and 6.3% for subgroup A. No statistically significant differences between the subgroups at any follow-up period were recorded in either morphological characteristics or clinical outcomes. CONCLUSIONS: The ability to lordotize a segment by stand-alone ACDF is below the angular resolution of current radiographic methods, irrespective of the sagittal profile of the implant used. Comparable morphological results haven't been reflected by significant difference in subjective and clinical outcome and also in the incidence of surgery for adjacent segment disease. Such results were not expected and therefore post-operative sagittal alignment mechanisms in stand alone cage assisted ACDF will require further investigation. Key words:cervical vertebrae, surgical technique, spinal fusion, sagittal alignment, clinical outcome. PMID- 25137500 TI - Epithelioid osteosarcoma of the scapula. AB - Epithelioid and epithelial neoplasms of bone are rare. They include different epithelioid variants of vascular lesions, osteoblastoma, chondroblastoma and most importantly metastatic carcinoma. Up to now, only few cases of epithelioid osteosarcoma were described. In this case the authors report a 53-year-old patient presented with a medical history of chronic shoulder pain for 3 years. Magnetic resonance imaging (MRI and computed tomography (CT) showed a destructive, partially calcified osseous lesion of the scapula with expansion into the surrounding soft tissue, suggestive of a primary bone tumor. Histologically, the tumor consisted of epithelioid cells with expression of cytokeratine and the lesion was primarily diagnosed as metastatic carcinoma. With regard to the MRI morphology untypical for metastatic disease the histopathologic slides were re-evaluated and detection of tumor osteoid led to the diagnosis of epithelioid osteosarcoma. Chemotherapy was initiated, however follow-up imaging studies showed rapidly progressive disease of both primary tumor and lung metastases. In conclusion, epithelioid neoplasms of the bone are extremetumourly rare and must be distinguished from metastatic carcinoma. Despite the presence of cytokeratine positive cells a thorough histological evaluation is mandatory and osteoid detection is essential in order to establish the correct diagnosis and further treatment. Key words: osteosarcoma, epithelioid, aneurysmal bone cyst, chondrosarcoma, pathology, immunohistochemistry. PMID- 25137501 TI - [Surgical treatment of ischial apophysis avulsion. Case report]. AB - The optimal management of ischial apophysis avulsion, especially indications for surgery, is not well defined. The authors present the case of a 16-year-old man who sustained an avulsion fracture of the ischial apophysis during his athlete training programme. The avulsion was diagnosed by X-ray. Because of displacement, surgery was indicated and open reduction with osteosynthesis was performed using a subgluteal approach on the eighth day after injury. Full weight bearing was allowed at nine weeks after injury, after the post-operative rehabilitation programme had been completed. Return to his sports activity was allowed at four months after injury. At one post-operative year the patient was free of any symptoms. The proper surgical treatment of a displaced ischial apophysis avulsion and subsequent rehabilitation allow for early full weight bearing, including sports activities. The subgluteal approach provides good access to the ischial tuberosity with a minimal risk of complications and a good cosmetic outcome. Key words:apophysis, ischial tuberosity, avulsion. PMID- 25137502 TI - Engineering the interfaces of ITO@Cu2S nanowire arrays toward efficient and stable counter electrodes for quantum-dot-sensitized solar cells. AB - Among the issues that restrict the power conversion efficiency (PCE) of quantum dot-sensitized solar cells (QDSSCs), insufficient catalytic activity and stability of counter electrodes (CEs) are critical but challenging ones. The state-of-the-art Cu/Cu2S CEs still suffer from mechanical instability and uncertainty due to the reaction of copper and electrolyte. Herein, ITO@Cu2S core shell nanowire arrays were developed to fabricate CEs for QDSSCs, which have no such issues in Cu/Cu2S CEs. These nanowire arrays exhibited small charge transfer resistance and sheet resistance, and provided more active catalytic sites and easy accessibility for electrolyte due to the three-dimensional structure upon use as CEs. More interestingly, it was found that the interface of ITO/Cu2S significantly affected the performance of ITO@Cu2S nanowire array CEs. By varying synthetic methods, a series of ITO@Cu2S nanowire arrays were prepared to investigate the influence of ITO/Cu2S interface on their performance. The results showed that ITO@Cu2S nanowire array CEs with a continuous Cu2S nanocrystal shell fabricated via an improved cation exchange route exhibited excellent and thickness-dependent performance. The PCE of corresponding QDSSCs increased by 11.6 and 16.5% compared to that with the discrete Cu2S nanocrystal and the classic Cu/Cu2S CE, respectively, indicating its promising potential as a new type of CE for QDSSCs. PMID- 25137503 TI - A silver nanoparticle embedded hydrogel as a substrate for surface contamination analysis by surface-enhanced Raman scattering. AB - A surface enhanced Raman scattering (SERS) substrate, capable of extracting small amounts of organic species from surfaces of different types of materials with variable roughness, has been fabricated. The substrate consists of Ag NPs encapsulated in poly(vinyl alcohol) (PVA) hydrogels, commonly known as PVA "slime". Unlike traditional SERS substrates, such as colloidal suspensions, the resulting PVA slime SERS substrate presents good viscoelasticity, allowing it to conform to the surface of various materials of arbitrary roughness. Surfaces of different materials, including sandpapers, cotton, metal, and wood, previously contaminated with nile blue A (NBA) were analyzed with the PVA slime SERS substrate. Limits of detection (LOD) as low as 100 ppb (0.79 ng in a total amount on an area of ~3 cm(2)) were achieved for all surfaces tested. Pesticides and Sudan red III on the glass surface have also been detected, with a LOD of 1.6 ng per ~3 cm(2). PMID- 25137504 TI - From theory to evidence: long-term evaluation of the mechanism of action and flap integration of distal vascularized lymph node transfers. AB - BACKGROUND: Nonanatomic (distal) placement of vascularized lymph node (VLN) transfers have shown efficacy in the treatment of extremity lymphedema, but the mechanism by which these flaps provide relief of lymphedema remains unclear. Intrinsic lymphovenous connections have been previously shown to exist in the transferred flap. But, the long-term interaction of the VLN flap and surrounding lymphedematous extremity has not been previously investigated. PATIENTS AND METHODS: A retrospective review of a prospective maintained database of patients who underwent VLN transfer was evaluated. Patients who underwent distal VLN transfer and had more than 1-year follow-up were identified. Lymphodynamic evaluation was performed using 0.3 to 0.6 mL indocyanine green (ICG) injection at 5 cm proximal to the flap edge on identified patients. Migration direction of dye and latency period was evaluated. RESULTS: In total, 20 patients were identified who met inclusion criteria. Average long-term follow-up was 27.3 months. The average circumference reduction of the affected extremity was 40.5%. ICG appearance within the VLN flap was found in all patients occurring on average in 178.3 seconds. In all cases, flow occurred in the distal direction (toward the flap) with proximal placement of dye. Latency period was found to inversely correlate with circumference reduction (p < 0.01). CONCLUSIONS: Distal, nonanatomic placement of VLN flaps provide sustained limb circumference reduction in extremity lymphedema patients following a minimum of 1-year postoperatively. Flap integration with the recipient site reliably occurs as witnessed with consistent ICG drainage, and occurs in the gravity-dependent direction. Faster clearance of ICG will result in improved clinical limb circumference reduction. PMID- 25137505 TI - Vitamin D and skeletal muscle function in athletes. AB - PURPOSE OF REVIEW: To highlight recently published data about the vitamin D status of athletes, and effect of vitamin D supplementation on muscle strength and performance in the athletic population.The vitamin D receptor exists in skeletal muscle, and muscle weakness has been reported in individuals who are severely deficient [25(OH)D <25 nmol/l]. Experimental findings reveal the cellular and genomic mechanisms implicating vitamin D in muscle mass, strength and function, and raise questions about the role of vitamin D in the achievement of optimum athletic performance. RECENT FINDINGS: Athletes appear to have the same risk of vitamin D deficiency and seasonal variance in status as nonathletic members of the same population, with the exception of athletes who train and compete indoors whose risk of deficiency is somewhat greater. Interventions with vitamin D supplements have had mixed results, with a positive effect on muscle function observed only in participants with insufficient status [25(OH)D <50 nmol/l]. SUMMARY: There have been relatively few robust interventions with vitamin D supplementation in athletic populations who are vitamin D deficient, and none which have been able to establish the ideal 25(OH)D concentration for optimum performance. PMID- 25137506 TI - Development of personalized functional foods needs metabolic profiling. AB - PURPOSE OF REVIEW: There is growing interest in applying metabolic profiling technologies to food science as this approach is now embedded into the foodomics toolbox. This review aims at exploring how metabolic profiling can be applied to the development of functional foods. RECENT FINDINGS: One of the biggest challenges of modern nutrition is to propose a healthy diet to populations worldwide that must suit high inter-individual variability driven by complex gene nutrient-environment interactions. Although a number of functional foods are now proposed in support of a healthy diet, a one-size-fits-all approach to nutrition is inappropriate and new personalized functional foods are necessary. Metabolic profiling technologies can assist at various levels of the development of functional foods, from screening for food composition to identification of new biomarkers of food intake to support diet intervention and epidemiological studies. SUMMARY: Modern 'omics' technologies, including metabolic profiling, will support the development of new personalized functional foods of high relevance to 21st century medical challenges, such as controlling the worldwide spread of metabolic disorders and ensuring healthy ageing. PMID- 25137507 TI - High-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of polycystic ovary syndrome in Indian adolescent women with polycystic ovary syndrome (PCOS). AB - C-reactive protein (CRP) is a risk marker for type 2 diabetes mellitus and cardiovascular diseases. In polycystic ovary syndrome (PCOS), limited data are available on high-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of PCOS especially in Indian women. The objective was to determine serum hs-CRP concentration in adolescent women with and without PCOS and to assess possible correlations of serum hs-CRP levels with components of PCOS in Indian women. One hundred and sixty women with PCOS and sixty non-PCOS women having normal menstrual cycles were included. Clinical assessment included anthropometry, Ferriman-Gallwey (FG) score and blood pressure (BP) measurement. Laboratory evaluation included estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, hs-CRP, lipid profile, and insulin, and glucose after 2-h oral glucose tolerance test. Homeostasis Model Assessment Insulin resistance index (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) and glucose intolerance was calculated. FG score, LH, FSH, total Testosterone, HOMA-IR and QUICKI were significantly different among women with or without PCOS (p < 0.01). Although hs-CRP levels showed a higher trend in women having PCOS, there was no significant difference between the groups (p > 0.05). A significant and positive correlation was found between hs-CRP and body mass index (BMI) (r = 0.308, p < 0.01) among PCOS group. The results in Indian adolescent women suggest that hs-CRP levels may not per se be associated with PCOS, rather can be related to fat mass in this subset of subjects. PMID- 25137508 TI - Discordant phenotype in monozygotic female twins with Lys35Thr TTR familial amyloidotic polyneuropathy. AB - Familial amyloidotic polyneuropathy is the hereditary form of transthyretin amyloidosis that is rapidly progressive. Discordant expression of Val30Met transthyretin amyloid in monozygotic twins has been reported in the past, in Europe and Asia. We report the first case of discordant expression of Lys35Thr transthyretin amyloid in female monozygotic twins in North America with eye involvement and peripheral neuropathy. PMID- 25137509 TI - Dermatomyositis-associated sensory neuropathy: a unifying pathogenic hypothesis. AB - Neuropathy as extramuscular manifestation of dermatomyositis (DM) is controversial due to uncommon occurrence, heterogeneity of associated nerve pathology, and lack of unifying pathogenetic mechanism(s). We describe a patient with classic manifestations of DM and extramuscular manifestation of neuropathy. Nerve pathology showed deposits of terminal complement complex (C5b-9). Her examination showed mild proximal weakness, rash, and sensory impairment in fingertips, toes, and nose. EMG/NCS revealed irritable myopathy and mild sensory neuropathy. Muscle biopsy showed features suggestive of DM, including deposition of C5b-9. CK was elevated to 214 and ANA was positive at 1:160. Etiological work up for neuropathy, including diabetes, was negative. Sural nerve biopsy at light level revealed very mild large fiber sensory neuropathy. EM showed moderately severe involvement of small sensory fibers. Neuropathy may be an underrecognized manifestation of DM. Nerve pathology demonstrating complement-mediated damage could be a unifying mechanism of muscle and nerve injury. PMID- 25137510 TI - Small fiber abnormalities in skin biopsies of patients with benign fasciculations. AB - OBJECTIVE: To determine whether patients with benign fasciculations have evidence for axonal loss in skin biopsies. METHODS: Epidermal sensory and sweat gland nerve fiber densities were quantified in skin biopsies of 11 patients with benign fasciculations and no other known cause for neuropathy. RESULTS: Nine of the 11 patients (82%) had significantly reduced epidermal or sweat gland nerve fiber densities at the calf or thigh, in comparison with control values. CONCLUSIONS: The presence of reduced epidermal and sweat gland nerve fiber density indicates the presence of axonal loss in patients with benign fasciculations. PMID- 25137511 TI - Neuromuscular pathology case. PMID- 25137512 TI - Rare case of a localized radial nerve amyloid neuropathy. AB - We report the case of a 55-year-old woman with a 6-month history of progressive paresis of the right radial nerve. Perioperative imaging detected a spindle shaped expansion of the radial nerve caused by an isolated local deposit of amyloid (amyloidoma). The deposit was resected in 2 phases and the resulting defect was bridged by a sural nerve autograft. Overall internal and hematological examination did not reveal systemic amyloidosis or lymphoproliferative disorder. The reason for our report is that localized forms of amyloid neuropathy are very rare. PMID- 25137513 TI - Spinal magnetic resonance imaging in chronic poliomyelitis. PMID- 25137514 TI - Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess. AB - Pyridoxine deficiency and excess have been implicated as a cause for peripheral neuropathy. As a result, unrelated neuropathies are often treated with pyridoxine based on questionable evidence. However, neurological practitioners frequently discourage patients from taking pyridoxine in excess of 50 mg/d given concerns around the development of a toxic sensory neuronopathy. There is no systematic review to support either of the 2 practices. To address this gap in knowledge, we reviewed the available literature on neuropathy attributed to pyridoxine deficiency and excess. Based on the current limited data, it can be concluded that very low doses of daily pyridoxine are required to prevent peripheral neuropathy. There is inadequate evidence to support routine pyridoxine supplementation in patients with disorders of peripheral nervous system. Supplementation with pyridoxine at doses greater than 50 mg/d for extended duration may be harmful and should be discouraged. PMID- 25137516 TI - Appearance of thymoma 5 years after thymectomy for nonthymomatous myasthenia gravis. PMID- 25137517 TI - A case of an African American man with ataxia and oculomotor apraxia 2. PMID- 25137518 TI - Solid-phase microextraction of phthalate esters by a new coating based on a thermally stable polypyrrole/graphene oxide composite. AB - A novel polypyrole/graphene oxide coating was made by the electrochemical polymerization of pyrrole in the presence of sodium dodecyl sulfate and graphene oxide on a platinum wire. The prepared fiber has shown a good thermal stability up to 300 degrees C. The fiber was applied to the direct solid-phase microextraction and gas chromatographic analysis of four phthalate esters. The effect of four parameters on gas chromatography peak area including extraction temperature, extraction time, injection temperature, and ionic strength were investigated. Under the optimized conditions, the detection limits were between 0.042 and 0.26 MUg/L. The intraday and interday relative standard deviations obtained at 55 MUg/L, using a single fiber, were 8.2-16% and 17.3-25.6%, respectively. The method was successfully applied to the analysis of phthalate esters in two real samples of boiling water in cheap disposable clear plastic drinking cups showing recoveries from 83 to 120%. PMID- 25137519 TI - Advance in PD research explored a new field on ubiquitin biology. PMID- 25137520 TI - Heavy metals, organic solvents, and multiple sclerosis: An exploratory look at gene-environment interactions. AB - Exposure to heavy metals and organic solvents are potential etiologic factors for multiple sclerosis (MS), but their interaction with MS-associated genes is under studied. The authors explored the relationship between environmental exposure to lead, mercury, and solvents and 58 single-nucleotide polymorphisms (SNPs) in MS associated genes. Data from a population-based case-control study of 217 prevalent MS cases and 496 age-, race-, gender-, and geographically matched controls were used to fit conditional logistic regression models of the association between the chemical, gene, and MS, adjusting for education and ancestry. MS cases were more likely than controls to report lead (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.07, 3.86) and mercury exposure (OR = 2.06; 95% CI: 1.08, 3.91). Findings of potential gene-environment interactions between SNPs in TNF-alpha, TNF-beta, TCA-beta, VDR, MBP, and APOE, and lead, mercury, or solvents should be considered cautiously due to limited sample size. PMID- 25137522 TI - Safety of minimally invasive radical prostatectomy in patients with prior abdominopelvic or inguinal surgery. AB - INTRODUCTION: Despite the widespread use of minimally invasive radical prostatectomy (MIRP), there remain concerns regarding its safety in patients with a history of prior abdominopelvic or inguinal surgery. METHODS: A prospective database of 1165 MIRP procedures performed by a single surgeon at a high-volume tertiary care center from 2001 to 2013 was analyzed. After an initial period of transperitoneal MIRP (TP), an extraperitoneal (EP) approach was used preferentially beginning in 2005 (for both laparoscopic and robotic cases), and robotics were used preferentially beginning in 2010. Overall perioperative complications, major complications (Clavien-Dindo III or IV), and abdominal complications (e.g., ileus, bowel/organ injury, or vascular injury) were compared for patients with and without a prior surgical history. Uni- and multivariate logistic regression were used to control the impact of robotics, approach, operative time, estimated blood loss, case number, prostate weight, and primary Gleason on complications. RESULTS: Three hundred patients undergoing MIRP had prior abdominopelvic or inguinal surgery (25.8%). Of these, 102 (34%) underwent TP and 198 (66%) EP MIRP. Robotics was used in 286 cases (24.6%) and pure laparoscopy in 879 (75.4%). Complications occurred in 111 patients (9.5%) from the total cohort, with major complications in 32 (2.75%) and abdominal complications in 19 (1.63%). Prior surgery was not associated with overall, major, or abdominal complications. Of the controlling factors, only increasing operative time was associated with postoperative abdominal complications (most of which were ileus) on multivariate analysis. CONCLUSIONS: In this large single surgeon series where both EP and TP approaches to MIRP are utilized, prior abdominopelvic or inguinal surgery was not associated with an increased risk of perioperative complications. PMID- 25137521 TI - Amide proton transfer-weighted imaging of the head and neck at 3 T: a feasibility study on healthy human subjects and patients with head and neck cancer. AB - The aim of this study was to explore the feasibility and repeatability of amide proton transfer-weighted (APTw) MRI for the head and neck on clinical MRI scanners. Six healthy volunteers and four patients with head and neck tumors underwent APTw MRI scanning at 3 T. The APTw signal was quantified by the asymmetric magnetization transfer ratio (MTRasym) at 3.5 ppm. Z spectra of normal tissues in the head and neck (masseter muscle, parotid glands, submandibular glands and thyroid glands) were analyzed in healthy volunteers. Inter-scan repeatability of APTw MRI was evaluated in six healthy volunteers. Z spectra of patients with head and neck tumors were produced and APTw signals in these tumors were analyzed. APTw MRI scanning was successful for all 10 subjects. The parotid glands showed the highest APTw signal (~7.6% average), whereas the APTw signals in other tissues were relatively moderate. The repeatability of APTw signals from the masseter muscle, parotid gland, submandibular gland and thyroid gland of healthy volunteers was established. Four head and neck tumors showed positive mean APTw ranging from 1.2% to 3.2%, distinguishable from surrounding normal tissues. APTw MRI was feasible for use in the head and neck regions at 3 T. The preliminary results on patients with head and neck tumors indicated the potential of APTw MRI for clinical applications. PMID- 25137523 TI - Hemostatic effect of hot saline irrigation during functional endoscopic sinus surgery: a randomized controlled trial. AB - BACKGROUND: The endoscopically magnified operative field in functional endoscopic sinus surgery (FESS) makes even a small amount of bleeding a potentially significant hindrance. It is thought that irrigation with hot saline during surgery may improve surgical field of view by producing a hemostatic effect. Our objective was to assess the effectiveness of hot saline irrigation (HSI) compared to room temperature saline irrigation (RTSI) in the control of intraoperative bleeding during FESS. METHODS: Sixty-two chronic rhinosinusitis (CRS) patients undergoing FESS were randomized to 2 treatment arms in an equal ratio. Subjects received either HSI (49 degrees C) or RTSI (18 degrees C), 20 mL every 10 minutes, for the duration of FESS. The Boezaart endoscopic field of view grading system was the primary outcome measure. Boezaart score, heart rate, and mean arterial blood pressure (MABP) were recorded at 10-minute intervals between irrigations. RESULTS: Mean endoscopic surgical field of view (Boezaart score) did not significantly differ between the HSI and RTSI groups (1.5 +/- 0.6 vs 1.3 +/- 0.5; p = 0.23). However, when FESS was longer than 2 hours in duration, the Boezaart scores were significantly better in the HSI group (1.6 +/- 0.6 vs 1.2 +/ 0.4; p = 0.04). We found that blood loss per minute was significantly reduced (p = 0.02) in all cases in which HSI was used (2.3 +/- 1.0) compared to RTSI (1.7 +/ 1.1). Despite this, heart rate (p = 0.32) and MABP (p = 0.14) did not significantly differ between treatment groups. CONCLUSION: HSI may be beneficial in improving surgical field of view in FESS after 2 hours of operating time. A significant reduction in rate of blood loss may be attained with HSI. PMID- 25137524 TI - Direct comparison of electrochemical and spectrochemical kinetics for catalytic oxygen reduction. AB - We describe here a direct comparison of electrochemical and spectrochemical experiments to determine rates and selectivity of oxygen reduction catalyzed by iron 5,10,15,20-meso-tetraphenylporphyrin chloride. Good agreement was found between the two methods, suggesting the same mechanism is occurring under both conditions, with the same third-order rate law, similar selectivity, and the derived rate constants agreeing within a factor of at most 4, with k(cat) ? 2 * 10(6) M(-2) s(-1). This Communication provides a rare example of a redox catalytic process characterized by two common but very different methods. PMID- 25137525 TI - Surface-initiated hyperbranched polyglycerol as an ultralow-fouling coating on glass, silicon, and porous silicon substrates. AB - Anionic ring-opening polymerization of glycidol was initiated from activated glass, silicon, and porous silicon substrates to yield thin, ultralow-fouling hyperbranched polyglycerol (HPG) graft polymer coatings. Substrates were activated by deprotonation of surface-bound silanol functionalities. HPG polymerization was initiated upon the addition of freshly distilled glycidol to yield films in the nanometer thickness range. X-ray photoelectron spectroscopy, contact angle measurements, and ellipsometry were used to characterize the resulting coatings. The antifouling properties of HPG-coated surfaces were evaluated in terms of protein adsorption and the attachment of mammalian cells. The adsorption of bovine serum albumin and collagen type I was found to be reduced by as much as 97 and 91%, respectively, in comparison to untreated surfaces. Human glioblastoma and mouse fibroblast attachment was reduced by 99 and 98%, respectively. HPG-grafted substrates outperformed polyethylene glycol (PEG) grafted substrates of comparable thickness under the same incubation conditions. Our results demonstrate the effectiveness of antifouling HPG graft polymer coatings on a selected range of substrate materials and open the door for their use in biomedical applications. PMID- 25137526 TI - Catalytic mechanism of bacteriophage T4 Rad50 ATP hydrolysis. AB - Spontaneous double-strand breaks (DSBs) are one of the most deleterious forms of DNA damage, and their improper repair can lead to cellular dysfunction. The Mre11 and Rad50 proteins, a nuclease and an ATPase, respectively, form a well-conserved complex that is involved in the initial processing of DSBs. Here we examine the kinetic and catalytic mechanism of ATP hydrolysis by T4 Rad50 (gp46) in the presence and absence of Mre11 (gp47) and DNA. Single-turnover and pre-steady state kinetics on the wild-type protein indicate that the rate-limiting step for Rad50, the MR complex, and the MR-DNA complex is either chemistry or a conformational change prior to catalysis. Pre-steady state product release kinetics, coupled with viscosity steady state kinetics, also supports that the binding of DNA to the MR complex does not alter the rate-limiting step. The lack of a positive deuterium solvent isotope effect for the wild type and several active site mutants, combined with pH-rate profiles, implies that chemistry is rate-limiting and the ATPase mechanism proceeds via an asymmetric, dissociative like transition state. Mutation of the Walker A/B and H-loop residues also affects the allosteric communication between Rad50 active sites, suggesting possible routes for cooperativity between the ATP active sites. PMID- 25137527 TI - Introduction of a methodology for visualization and graphical interpretation of Bayesian classification models. AB - Supervised machine learning models are widely used in chemoinformatics, especially for the prediction of new active compounds or targets of known actives. Bayesian classification methods are among the most popular machine learning approaches for the prediction of activity from chemical structure. Much work has focused on predicting structure-activity relationships (SARs) on the basis of experimental training data. By contrast, only a few efforts have thus far been made to rationalize the performance of Bayesian or other supervised machine learning models and better understand why they might succeed or fail. In this study, we introduce an intuitive approach for the visualization and graphical interpretation of naive Bayesian classification models. Parameters derived during supervised learning are visualized and interactively analyzed to gain insights into model performance and identify features that determine predictions. The methodology is introduced in detail and applied to assess Bayesian modeling efforts and predictions on compound data sets of varying structural complexity. Different classification models and features determining their performance are characterized in detail. A prototypic implementation of the approach is provided. PMID- 25137528 TI - Strong negative nanocatalysis: oxygen reduction and hydrogen evolution at very small (2 nm) gold nanoparticles. AB - The electron transfer kinetics associated with both the reduction of oxygen and of protons to form hydrogen at gold nanoparticles are shown to display strong retardation when studied at citrate capped ultra small (2 nm) gold nanoparticles. Negative nanocatalysis in the hydrogen evolution reaction (HER) is reported for the first time. PMID- 25137530 TI - HPLC-UV method for quantifying etoposide in plasma and tumor interstitial fluid by microdialysis: application to pharmacokinetic studies. AB - A simple and sensitive bioanalytical method was developed and validated for determination of etoposide in plasma and microdialysis samples of Walker-256 tumor-bearing rats. A microdialysis probe was implanted in the center of a subcutaneous tumor and Ringer's solution was used as perfusion medium. Chromatographic separation was conducted on a Shimadzu CLC-C8 column using a mobile phase consisting of water-acetonitrile (70:30; v/v) adjusted to pH 4.0 +/- 0.1 with formic acid at a gradient flow rate of 1.0-0.6 mL/min, an injection volume of 30 MUL and UV detection at 210 nm. Microdialysate samples were analyzed without processing and plasma samples (100 MUL) were spiked with phenytoin as internal standard (IS) (1 ug/mL) followed by extraction with tert-butyl methyl ether. The organic layer was evaporated and reconstituted with 100 MUL of mobile phase before injection. The methods for plasma and microdialysate were linear in the ranges of 25-10,000 ng/mL and of 10-1500 ng/mL, respectively. All the validation parameters such as intra- and inter-day precision and accuracy and stability were within the limits established by international guidelines. The present method was successfully applied in the investigation of etoposide pharmacokinetics in rat plasma and microdialysate tumor samples following a single 15 mg/kg intravenous dose. PMID- 25137529 TI - Iminosugar C-glycoside analogues of alpha-D-GlcNAc-1-phosphate: synthesis and bacterial transglycosylase inhibition. AB - We herein describe the first synthesis of iminosugar C-glycosides of alpha-D GlcNAc-1-phosphate in 10 steps starting from unprotected D-GlcNAc. A diastereoselective intramolecular iodoamination-cyclization as the key step was employed to construct the central piperidine ring of the iminosugar and the C glycosidic structure of alpha-D-GlcNAc. Finally, the iminosugar phosphonate and its elongated phosphate analogue were accessed. These phosphorus-containing iminosugars were coupled efficiently with lipophilic monophosphates to give lipid linked pyrophosphate derivatives, which are lipid II mimetics endowed with potent inhibitory properties toward bacterial transglycosylases (TGase). PMID- 25137532 TI - Halide-bridged binuclear HX-splitting catalysts. AB - Two-electron mixed-valence compounds promote the rearrangement of the two electron bond photochemically. Such complexes are especially effective at managing the activation of hydrohalic acids (HX). Closed HX-splitting cycles require proton reduction to H2 and halide oxidation to X2 to be both accomplished, the latter of which is thermodynamically and kinetically demanding. Phosphazane-bridged Rh2 catalysts have been especially effective at activating HX via photogenerated ligand-bridged intermediates; such intermediates are analogues of the classical ligand-bridged intermediates proposed in binuclear elimination reactions. Herein, a new family of phosphazane-bridged Rh2 photocatalysts has been developed where the halide-bridged geometry is designed into the ground state. The targeted geometries were accessed by replacing previously used alkyl isocyanides with aryl isocyanide ligands, which provided access to families of Rh2L1 complexes. H2 evolution with Rh2 catalysts typically proceeds via two electron photoreduction, protonation to afford Rh hydrides, and photochemical H2 evolution. Herein, we have directly observed each of these steps in stoichiometric reactions. Reactivity differences between Rh2 chloride and bromide complexes have been delineated. H2 evolution from both HCl and HBr proceeds with a halide-bridged Rh2 hydride photoresting state. The H2-evolution efficiency of the new family of halide-bridged catalysts is compared to a related catalyst in which ligand-bridged geometries are not stabilized in the molecular ground state, and the new complexes are found to more efficiently facilitate H2 evolution. PMID- 25137531 TI - EPR, ENDOR, and electronic structure studies of the Jahn-Teller distortion in an Fe(V) nitride. AB - The recently synthesized and isolated low-coordinate Fe(V) nitride complex has numerous implications as a model for high-oxidation states in biological and industrial systems. The trigonal [PhB((t)BuIm)3Fe(V)=N](+) (where (PhB((t)BuIm)3( ) = phenyltris(3-tert-butylimidazol-2-ylidene)), (1) low-spin d(3) (S = 1/2) coordination compound is subject to a Jahn-Teller (JT) distortion of its doubly degenerate (2)E ground state. The electronic structure of this complex is analyzed by a combination of extended versions of the formal two-orbital pseudo Jahn-Teller (PJT) treatment and of quantum chemical computations of the PJT effect. The formal treatment is extended to incorporate mixing of the two e orbital doublets (30%) that results from a lowering of the idealized molecular symmetry from D3h to C3v through strong "doming" of the Fe-C3 core. Correspondingly we introduce novel DFT/CASSCF computational methods in the computation of electronic structure, which reveal a quadratic JT distortion and significant e-e mixing, thus reaching a new level of synergism between computational and formal treatments. Hyperfine and quadrupole tensors are obtained by pulsed 35 GHz ENDOR measurements for the (14/15)N-nitride and the (11)B axial ligands, and spectra are obtained from the imidazole-2-ylidene (13)C atoms that are not bound to Fe. Analysis of the nitride ENDOR tensors surprisingly reveals an essentially spherical nitride trianion bound to Fe, with negative spin density and minimal charge density anisotropy. The four-coordinate (11)B, as expected, exhibits negligible bonding to Fe. A detailed analysis of the frontier orbitals provided by the electronic structure calculations provides insight into the reactivity of 1: JT-induced symmetry lowering provides an orbital selection mechanism for proton or H atom transfer reactivity. PMID- 25137533 TI - Chronic lung disease and detection of pulmonary artery dilatation in high resolution computerized tomography of chest in chronic arsenic exposure. AB - Lung affection in chronic arsenicosis developing from chronic ingestion of arsenic contaminated groundwater has been known but little is known on its effect on pulmonary arterial system. A cross sectional study was carried out at two geographically similar areas and demographically similar populations with or without evidence of chronic arsenic exposure in West Bengal, India. The willing participants in both the groups with chronic respiratory symptoms were evaluated with High Resolution Computerized Tomography (HRCT) of Chest. Evaluation of High Resolution Computerized Tomography of chest followed clinical assessment of lung disease in194 and 196 subjects from the arsenic exposed and unexposed people; the former had a higher prevalence of cough OR(Odds Ratio) 3.23 (95% CI(Confidence Interval): 1.72-6.07) and shortness of breath OR1.76 (95% CI: 0.84-3.71), respectively. The arsenic exposed individuals showed higher score for bronchiectasis [mean +/- SD(Standard Deviation)] as 2.41 +/- 2.32 vs. 1.22 +/- 1.48 (P <0.001), pulmonary artery branch dilatation (PAD) as 2.48 +/- 2.33 vs. 0.78 +/- 1.56, (P <0.001) and pulmonary trunk dilatation as 0.26 +/- 0.45 vs. nil. Age-adjusted prevalence odds ratio (POR) for Pulmonary Artery Dilatation Found in HRCT comparing those exposed to arsenic (Group 1) to unexposed participants (Group 2) was found to be 6.98 (CI: 2.26-16.48). There was a strong dose-response relationship between the PAD (Pulmonary Artery Dilatation) and cumulative arsenic exposure. Pulmonary trunk and branch dilatation in chronic arsenicosis is a frequent abnormality seen in HRCT Chest of arsenicosis patients. The significance of such finding needs further investigation. PMID- 25137534 TI - Adsorption and removal of arsenic (V) using crystalline manganese (II,III) oxide: Kinetics, equilibrium, effect of pH and ionic strength. AB - Manganese (II,III) oxide (Mn3O4) crystalline powder was evaluated as a potential sorbent for removal of arsenic (V) from water. Adsorption isotherm experiments were carried out to determine the adsorption capacity using de-ionized (DI) water, a synthetic solution containing bicarbonate alkalinity, and two natual groundwater samples. Adsorption isotherm data followed the Langmuir and Freundlich equations, indicating favorable adsorption of arsenic (V) onto Mn3O4, while results from the Dubinin-Radushkevich equation were suggestive of chemisorption of arsenic (V). When normalized to the sorbent surface area, the maximum adsorption capacity of Mn3O4 for arsenic (V) was 101 MUg m(-2), comparable to that of activated alumina. Arsenic (V) adsorption onto Mn3O4 followed pseudo-second-order kinetics. Adsorption of arsenic (V) was greatest at pH 2, while adsorption at pH 7-9 was within 91% of maximum adsorption, whereas adsorption decreased to 32% of maximum adsorption at pH 10. Surface charge analysis confirmed the adsorption of arsenic (V) onto the acidic surface of the Mn3O4 sorbent with a pHPZC of 7.32. The presence of coexisting ions bicarbonate and phosphate resulted in a decrease in arsenic (V) uptake. Comparable adsorption capacities were obtained for the synthetic solution and both groundwater samples. Overall, crystalline Mn3O4 was an effective and viable sorbent for removal of arsenic (V) from natural water, removing greater than 95% of arsenic (V) from a 1 mg L(-1) solution within 60 min of contact time. PMID- 25137535 TI - Kinetic study of adsorption of arsenic onto New Zealand Ironsand (NZIS). AB - New Zealand Ironsand (NZIS), an iron-rich sand ubiquitous to the coast of the North Island of New Zealand was examined for the removal of arsenic (both As (III) and As (V)) by adsorption. Batch experiments were performed to evaluate the adsorption kinetics at three different pH conditions (3.0, 7.5 and 11.0). In addition, a column test was conducted to obtain the breakthrough curve and appraise the arsenic removal capacity of NZIS used as a filter media. The kinetic study showed that a very long contact time (>144 h) was needed to reach equilibrium and the nature of the adsorption was well described (R(2) value more than 0.96 at each pH condition) with a pseudo-second-order adsorption kinetic model for both As (III) and As (V). In column tests, a pore volume (PV) of 700 and 400 yielded a total arsenic level less than the WHO guideline value of 10 MUg/L for As (III) and As (V), respectively. PMID- 25137536 TI - Characterization of arsenite-oxidizing bacteria isolated from arsenic contaminated groundwater of West Bengal. AB - Nine arsenic (As)-resistant bacterial strains isolated from As-rich groundwater samples of West Bengal were characterized to elucidate their potential in geomicrobial transformation and bioremediation aspects. The 16S rRNA gene-based phylogenetic analysis revealed that the strains were affiliated with genera Actinobacteria, Microbacterium, Pseudomonas and Rhizobium. The strains exhibited high resistance to As [Minimum inhibitory concentration (MIC) >= 10 mM As(3+) and MIC >= 450 mM As(5+)] and other heavy metals, e.g., Cu(2+), Cr(2+), Ni(2+), etc. (MIC >= 2 mM) as well as As transformation (As(3+) oxidation and As(5+) reduction) capabilities. Their ability to utilize diverse carbon source(s) including hydrocarbons and different alternative electron acceptor(s) (As(5+), SO4(2-), S2O3(2-), etc.) during anaerobic growth was noted. Growth at wide range of pH, temperature and salinity, production of siderophore and biofilm were observed. Together with these, growth pattern and transformation kinetics indicated a high As(3+) oxidation activity of the isolates Rhizobium sp. CAS934i, Microbacterium sp. CAS905i and Pseudomonas sp. CAS912i. A positive relation between high As(3+) resistance and As(3+) oxidation and the supportive role of As(3+) in bacterial growth was noted. The results highlighted As(3+) oxidation process and metabolic repertory of strains indigenous to contaminated groundwater and indicates their potential in As(3+) detoxification. Thus, such metabolically well equipped bacterial strains with highest As(3+) oxidation activities may be used for bioremediation of As contaminated water and effluents in the near future. PMID- 25137537 TI - Variation in composition and relative content of accumulated photopigments in a newly isolated Rhodobacter capsulatus strain XJ-1 in response to arsenic. AB - This study aimed to isolate and characterize a new arsenic (As)-tolerant bacterial strain (XJ-1) from the Halosol soil, to evaluate its As tolerance, and to examine the variation in composition and relative content of accumulated photosynthetic pigments in response to As. The experiments were performed with high-performance liquid chromatography (HPLC), inductively-coupled plasma mass spectrometry (ICP-MS), liquid chromatography/mass spectrometry (LC/MS), thin layer chromatography (TLC) and grayscale intensity image analysis using Gel-Pro analyzer software. Strain XJ-1 was identified as Rhodobacter (R.) capsulatus based on 16S rRNA gene sequencing and physiological characteristics. Strain XJ-1 was able to grow when exposed to arsenite [As(III)] and arsenate [As(V)] under anaerobic-light conditions. The median effective concentrations (EC50) of As(III) and As(V) were 0.61 mM and 2.03 mM, respectively. Strain XJ-1 could reduce As(V) to As(III), but As(III) could not be transformed back to As(V) or other organic As compounds. Accumulation of bacteriochlorophylls and carotenoids in strain XJ-1 varied in the presence of 0.2-1.2 mM As(III) and 0-2.5 mM As(V). As exposure resulted in pronounced variation in compositions and contents of photosynthetic pigments, especially hydroxyspheroidene, bacteriophaeophytin, the ratio of tetrahydrogeranylgeranyl to phytylated BChl a, and the ratio of spheroidene to spheroidenone. This research highlights the adaptative response of R. capsulatus strain XJ-1 photosystems to environmental As, and demonstrates the potential of utilizing the sensitivity of its photosynthetic pigments to As(III) and As(V) for the biodetection of As in the environment. PMID- 25137538 TI - Amperometric determination of cadmium, lead, and mercury metal ions using a novel polymer immobilised horseradish peroxidase biosensor system. AB - This work was undertaken to develop a novel Pt/PANI-co-PDTDA/HRP biosensor system for environmental applications to investigate the inhibition studies by specific heavy metals, to provide data suitable for kinetic studies and further application of the biosensor to environmental samples. The newly constructed biosensor was compared to the data of the well-researched Pt/PANI/HRP biosensor. Optimised experimental conditions, such as the working pH for the biosensor was evaluated. The functionality of the amperometric enzyme sensor system was demonstrated by measuring the oxidation current of hydrogen peroxide followed by the development of an assay for determination of metal concentration in the presence of selected metal ions of Cd(2+), Pb(2+) and Hg(2+). The detection limits were found to be 8 * 10(-4) MUg L(-1) for cadmium, 9.38 * 10(-4) MUg L(-1) for lead and 7.89 * 10(-4) MUg L(-1) for mercury. The World Health Organisation recommended that the maximum safety level of these metals should not exceed 0.005 mg L(-1) of Cd(2+), 0.01 mg L(-1) of Pb(2+) and 0.001 mg L(-1) of Hg(2+.), respectively. The analytical and detection data for the metals investigated were observed to be lower than concentrations recommended by several bodies including World Health Organisation and Environmental Protection Agencies. Therefore the biosensors developed in this study can be used to screen the presence of these metals in water samples because of its low detection limit. The modes of inhibition of horseradish peroxidase by Pb(2+), Cd(2+) and Hg(2+) as analysed using the double reciprocal plots of the Michaelis-Menten equation was found to be reversible and uncompetitive inhibition. Based on the Km(app) and Imax values for both biosensors the results have shown smaller values. These results also proved that the enzyme modified electrode is valuable and can be deployed for the determination or screening of heavy metals. PMID- 25137540 TI - Strategies of management for the whole treatment of leachates generated in a landfill and in a composting plant. AB - This study compares the leachates generated in the treatment of Municipal Solid Wastes (MSW) of similar origin but managed in two different ways: (a) sorting and composting in a Treatment Plant in Aranda de Duero (Burgos, Spain), and (b) direct dumping in a landfill in Aranda de Duero (Burgos, Spain) with no prior treatment. Two different leachates were considered for the former: those generated in the fermentation shed (P1) and those generated in the composting tunnels (P2); another leachate was collected from the landfill (P3). Physical and chemical properties, including heavy metal contents, were seasonally monitored in the different leachates. This study allowed us to conclude that the sampling season had a significant effect on Pb, Cd, Ni, Mg and total-N contents (P < 0.01). Similarly, leachates P1, P2 and P3 exhibited significant overall differences for most of the measured parameters except for Cd, Cu, Pb, K, Fe, C inorg and C-org contents (P < 0.01). This study concludes with the feasibility of a whole treatment for both leachates using ultrafiltration in a membrane bioreactor (MBR). PMID- 25137539 TI - Removal of dicyclohexyl acetic acid from aqueous solution using ultrasound, ozone and their combination. AB - Naphthenic acids are a complex mixture of organic components, some of which include saturated alkyl-substituted cycloaliphatic carboxylic acids and acyclic aliphatic acids. They are naturally found in hydrocarbon deposits like oil sand, petroleum, bitumen and crude oil. In this study, the oxidation of a relatively high molecular weight naphthenic acid (Dicyclohexyl acetic acid) was investigated using ozonation, ultrasonication and hydrogen peroxide alone and their combinations. Effects on oxidation of dicyclohexyl acetic acid (DAA) were measured for different concentrations of ozone ranging between 0.7 to 3.3 mg L( 1) and pH in the range 6 to 10. Ultrasonication and hydrogen peroxide alone were not effective to oxidize dicyclohexyl acetic acid, but combining ultrasonication with H2O2 had a significant effect on oxidation of dicyclohexyl acetic acid with maximum removal reaching to 84 +/- 2.2% with 81 +/- 2.1% reduction in chemical oxygen demand (COD). Synergistic effects were observed for combining ultrasonication with ozonation and resulted in 100% DAA removal with 98 +/- 0.8% reduction in COD within 15 min at 3.3 mg L(-1) ozone concentration and 130 Watts ultrasonication power. The reaction conditions obtained for the maximum oxidation of DAA and COD removal were used for the degradation of naphthenic acids mixture extracted from oil sands process water (OSPW). The percentage oxidation of NAs mixture extracted from OSPW was 89.3 +/- 1.1% in ozonation and combined ozonation and ultrasonication, but COD removal observed was 65 +/- 1.2% and 78 +/- 1.4% for ozonation and combined ozonation and ultrasonication treatments, respectively. PMID- 25137541 TI - Cosmetic wastewater treatment using the Fenton, Photo-Fenton and H2O2/UV processes. AB - Advanced Oxidation Processes (AOPs), such as the Fenton, photo-Fenton and H2O2/UV processes, have been investigated for the treatment of cosmetic wastewaters that were previously coagulated by FeCl3. The Photo-Fenton process at pH 3.0 with 1000/100 mg L(-1) H2O2/Fe(2+) was the most effective (74.0% Chemical Oxygen Demand (COD) removal). The Fenton process with 1200/500 mg L(-1) H2O2/Fe(2+) achieved a COD removal of 72.0%, and the H2O2/UV process achieved a COD removal of 47.0%. Spreading the H2O2 doses over time to obtain optimal conditions did not improve COD removal. The kinetics of the Fenton and photo-Fenton processes may be described by the following equation: d[COD]/dt = -a[COD] t(m) (t represents time and a and m are constants). The rate of COD removal by the H2O2/UV process may be described by a second-order reaction equation. Head Space, Solid-Phase MicroExtraction, Gas Chromatography and Mass Spectrometry (HS-SPME-GC-MS) were used to identify 48 substances in precoagulated wastewater. Among these substances, 26 were fragrances. Under optimal AOP conditions, over 99% of the identified substances were removed in 120 min. PMID- 25137542 TI - Influence of parameters on the photocatalytic degradation of phenolic contaminants in wastewater using TiO2/UV system. AB - The photocatalytic degradation of phenol in aqueous suspension using commercial TiO2 powder (Degussa P-25) irradiated with UV light was investigated. Photodegradation was compared using a photocatalyst (TiO2 alone), direct photolysis (UV alone) and TiO2/UV in a single batch reactor with mercury lamp irradiation. The study focused on the influence of various operating parameters on phenol treatment efficiency, including catalyst dosage, initial concentration of phenol, temperature, pH and change in pH were systematically investigated. The highest phenol degradation rate was obtained at pH 9.0, temperature 60 degrees C and catalyst dose of 2 g L(-1) with higher mineralization efficiency (in terms of TOC reduction). Experimental results showed that under optimized conditions the phenol removal efficiency was 98% and 100% for the TiO2/UV and TiO2/UV/H2O2 system, respectively. No significant effect on addition of chloride and metal ions was observed. Photodegradation of phenol followed first-order kinetics. To test whether the phenol removal was possible for wastewater using a TiO2/UV system, the degradation study was conducted with the real obtained wastewater. The removal of phenol from obtained wastewater and the synthetic wastewater containing phenol was comparable. The TiO2/UV system developed here is expected to be useful for the treatment of wastewater containing phenol. PMID- 25137543 TI - Comparison of five wastewater COD fractionation methods for dynamic simulation of MBR systems. AB - Five different wastewater COD fractionation methods were employed for simulating an experimental MBR wastewater treatment plant using WEST. The predictions of dynamic simulations using as input the data obtained according to each influent characterization methodology were compared with the results of the experimental system and differences between experimental and predicted values were analyzed in order to select the fractionation method which provides the best fitting and minimizes errors. Three of these methods were based on the determination of the biodegradable fractions using respirometric assays of real wastewater filtered through 0.45- and 0.22-MUm pore size filters or adding a previous flocculation step before filtration. Moreover, a method based on physicochemical analyses and another one based on theoretical coefficients were also compared. Simulated system performance and effluent quality greatly depended upon the influent characterization and the proper model calibration. Thus the importance of selecting a suitable fractionation methodology is high, especially in MBR systems working at specific operational conditions that may alter COD fractions. In this study, MLSS in the bioreactors and sludge supernatant COD concentrations were better predicted when the influent characterization was based on respirometric methods. Both the method based on theoretical coefficients and the physicochemical method underestimated the particulate inert fraction and therefore, also the MLSS concentrations. Moreover, these results showed that for a correct effluent COD prediction in MBR systems, it is necessary to take into account that the membrane retained part of the soluble inert fraction. PMID- 25137544 TI - An integrated use of multiple biomarkers to investigate the individual and combined effect of copper and cadmium on the marine green mussel (Perna viridis). AB - The present study documents individual and combined sub-lethal effect of one redox active (copper) and one non-redox active (cadmium) metal on green mussel (Perna viridis). The mussels were exposed to 60 MUg L(-1) of Cu and 150 MUg L(-1) of Cd (individually and in combination) for 21 days. Histopathological and ultrastructural studies revealed significant metal induced alterations such as vacuolization, fusion of gill lamellae, enhance mucous deposition, hyperplasia and necrosis in gills. Antioxidant enzyme assays revealed significant increase in superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione peroxidase (GPx) activity. Similarly, single exposure to Cd and Cu caused significant induction in Malate dehydrogenase (MDH) activity. However, combined Cu+Cd exposure modulated suppression in MDH activity. Unlike MDH, Cu and Cd individual exposure resulted in a decrease in esterase (EST) activity, but their combined exposure caused an induction. Non-enzymatic biomarkers such as lipid peroxidation (LPO) and metallothionein (MT) levels showed no significant change in response to Cu exposure, whereas, individual Cd exposure or Cd exposure in combination with Cu caused significant changes in their levels. Comet assay revealed a significant increase in DNA damage upon metal exposure. These results indicate that Cu (redox active) and Cd (non-redox active) can induce measurable physiological, biochemical as well as genotoxic perturbations in mussels even at sub-lethal concentrations. A monitoring programme based on the biomarkers discussed here would be useful to study the effect of metal pollutants reaching the coastal waters. PMID- 25137545 TI - Efficacy of hair analysis for monitoring exposure to uranium: a mini-review. AB - In spite of the ease with which samples may be collected and the stability of the samples after collection, the use of hair mineral analysis for monitoring environmental exposures and evaluating heavy metal poisonings has remained controversial since its initial applications for these purposes in the early 1950s. Among the major arguments against using hair mineral analysis in general were the absence of biokinetic models and/or metabolic data that adequately described the incorporation of trace elements into the hair, the absence of correlations between the concentrations of trace elements in the hair and their concentrations in other tissues, the inability to distinguish between trace elements that were deposited in the hair endogenously and those that were deposited on the hair exogenously, the absence of reliable reference ranges for interpreting the results of hair mineral analysis and a lack of standard procedures for the collecting, preparing and analyzing the hair samples. The developments of the past two decades addressing these objections are reviewed here, and arguments supporting the use of hair analysis for monitoring environmental and/or occupational exposures to uranium are made on the basis of the information presented in this review. PMID- 25137546 TI - Ecotoxicity of silver nanomaterials in the aquatic environment: a review of literature and gaps in nano-toxicological research. AB - There has been extensive growth in nanoscale technology in the last few decades to such a degree that nanomaterials (NMs) have become a constituent in a wide range of commercial and domestic products. With NMs already in use in several consumer products, concerns have emerged regarding their potential adverse environmental impacts. Although research has been undertaken in order to minimise the gaps in our understanding of NMs in the environment, little is known about their bioavailability and toxicity in the aquatic environment. Nano-toxicology is defined as the study of the toxicity of nanomaterials. Nano-toxicology studies remain poorly and unevenly distributed. To date most of the research undertaken has been restricted to a narrow range of test species such as daphnids. Crabs are bio-indicators that can be used for toxicological research on NMs since they occupy a significant position in the aquatic food chain. In addition, they are often used in conventional ecotoxicological studies due to their high sensitivity to environmental stressors and are abundantly available. Because they are benthic organisms they are prone to contaminant uptake and bioaccumulation. To our knowledge the crab has never been used in nano-toxicological studies. In this context, an extensive review on published scientific literature on the ecotoxicity of silver NPs (AgNPs) on aquatic organisms was conducted. Some of the most common biomarkers used in ecotoxicological studies are described. Emphasis is placed on the use of biomarker responses in crabs as monitoring tools, as well as on its limitations. Additionally, the gaps in nano-toxicological research and recommendations for future research initiatives are addressed. PMID- 25137547 TI - Method to simultaneously determine the sphingosine 1-phosphate breakdown product (2E)-hexadecenal and its fatty acid derivatives using isotope-dilution HPLC electrospray ionization-quadrupole/time-of-flight mass spectrometry. AB - Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various physiological processes, can be irreversibly degraded by the membrane-bound S1P lyase (S1PL) yielding (2E)-hexadecenal and phosphoethanolamine. It is discussed that (2E)-hexadecenal is further oxidized to (2E)-hexadecenoic acid by the long chain fatty aldehyde dehydrogenase ALDH3A2 (also known as FALDH) prior to activation via coupling to coenzyme A (CoA). Inhibition or defects in these enzymes, S1PL or FALDH, result in severe immunological disorders or the Sjogren Larsson syndrome, respectively. Hence, it is of enormous importance to simultaneously determine the S1P breakdown product (2E)-hexadecenal and its fatty acid metabolites in biological samples. However, no method is available so far. Here, we present a sensitive and selective isotope-dilution high performance liquid chromatography-electrospray ionization-quadrupole/time-of-flight mass spectrometry method for simultaneous quantification of (2E)-hexadecenal and its fatty acid metabolites following derivatization with 2-diphenylacetyl-1,3 indandione-1-hydrazone and 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. Optimized conditions for sample derivatization, chromatographic separation, and MS/MS detection are presented as well as an extensive method validation. Finally, our method was successfully applied to biological samples. We found that (2E) hexadecenal is almost quantitatively oxidized to (2E)-hexadecenoic acid, that is further activated as verified by cotreatment of HepG2 cell lysates with (2E) hexadecenal and the acyl-CoA synthetase inhibitor triacsin C. Moreover, incubations of cell lysates with deuterated (2E)-hexadecenal revealed that no hexadecanoic acid is formed from the aldehyde. Thus, our method provides new insights into the sphingolipid metabolism and will be useful to investigate diseases known for abnormalities in long-chain fatty acid metabolism, e.g., the Sjogren-Larsson syndrome, in more detail. PMID- 25137548 TI - A Novel SHOC2 Variant in Rasopathy. AB - Rasopathies are a group of genetic disorders caused by germline mutations in multiple genes of the Extracellular signal-Regulated Kinases 1 and 2 (ERK1/2) pathway. The only previously identified missense mutation in SHOC2, a scaffold protein of the ERK1/2 pathway, led to Noonan-like syndrome with loose anagen hair. Here, we report a novel mutation in SHOC2(c.519G>A; p.M173I) that leads to a Rasopathy with clinical features partially overlapping those occurring in Noonan and cardiofaciocutaneous syndromes. Studies to clarify the significance of this SHOC2 variant revealed that the mutant protein has impaired capacity to interact with protein phosphatase 1c (PP1c), leading to insufficient activation of RAF-1 kinase. This SHOC2 variant thus is unable to fully rescue ERK1/2 activity in cells depleted of endogenous SHOC2. We conclude that SHOC2 mutations can cause a spectrum of Rasopathy phenotypes in heterozygous individuals. Importantly, our work suggests that individuals with mild Rasopathy symptoms may be underdiagnosed. PMID- 25137549 TI - Discovery of carbohybrid-based 2-aminopyrimidine analogues as a new class of rapid-acting antimalarial agents using image-based cytological profiling assay. AB - New antimalarial agents that exhibit multistage activities against drug-resistant strains of malaria parasites represent good starting points for developing next generation antimalarial therapies. To facilitate the progression of such agents into the development phase, we developed an image-based parasitological screening method for defining drug effects on different asexual life cycle stages of Plasmodium falciparum. High-throughput screening of a newly assembled diversity oriented synthetic library using this approach led to the identification of carbohybrid-based 2-aminopyrimidine compounds with fast-acting growth inhibitory activities against three laboratory strains of multidrug-resistant P. falciparum. Our structure-activity relationship study led to the identification of two derivatives (8aA and 11aA) as the most promising antimalarial candidates (mean EC50 of 0.130 and 0.096 MUM against all three P. falciparum strains, selectivity indices >600, microsomal stabilities >80%, and mouse malaria ED50 values of 0.32 and 0.12 mg/kg/day, respectively), targeting all major blood stages of multidrug resistant P. falciparum parasites. PMID- 25137550 TI - RBC transfusion in pediatric patients supported with extracorporeal membrane oxygenation: is there an impact on tissue oxygenation? AB - OBJECTIVE: To examine first the RBC transfusion practice in pediatric patients supported with extracorporeal membrane oxygenation and second the relationship between transfusion of RBCs and changes in mixed venous saturation (SvO2) and cerebral regional tissue oxygenation, as measured by near-infrared spectroscopy in patients supported with extracorporeal membrane oxygenation. DESIGN: Retrospective observational study. SETTING: Pediatric, cardiovascular, and neonatal ICUs of a tertiary care children's hospital. PATIENTS: All pediatric patients supported with extracorporeal membrane oxygenation between January 1, 2010, and December 31, 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 45 patients supported with extracorporeal membrane oxygenation. The median (interquartile range) phlebotomy during extracorporeal membrane oxygenation was 75 mL/kg (33, 149 mL/kg). A total of 617 transfusions were administered (median, 9 per patient; range = 1-57). RBC volumes transfused during extracorporeal membrane oxygenation support were 254 mL/kg (136, 557) and 267 mL/kg (187, 393; p = 0.82) for cardiac and noncardiac patients, respectively. Subtracting the volume of RBCs used for extracorporeal membrane oxygenation circuit priming, median RBC transfusion volumes were 131 and 80 mL/kg for cardiac and noncardiac patients, respectively (p = 0.26). The cardiac surgical patients received the most RBCs (529 vs 74 mL/kg for nonsurgical cardiac patients). The median hematocrit maintained during extracorporeal membrane oxygenation support was 37%, with no difference between cardiac and noncardiac patients. Patients supported with extracorporeal membrane oxygenation were exposed to a median of 10.9 (range, 3-43) individual donor RBC units. Most transfusions resulted in no significant change in either SvO2 or cerebral near-infrared spectroscopy. Only 5% of transfusions administered (31/617) resulted in an increase in SvO2 of more than 5%, whereas an increase in cerebral near-infrared spectroscopy of more than 5 was only observed in 9% of transfusions (53/617). Most transfusions (73%) were administered at a time when the pretransfusion SvO2 was more than 70%. CONCLUSIONS: Patients supported with extracorporeal membrane oxygenation were exposed to large RBC transfusion volumes for treatment of mild anemia resulting from blood loss, particularly phlebotomy. In the majority of events, RBC transfusion did not significantly alter global tissue oxygenation, as assessed by changes in SvO2 and cerebral near-infrared spectroscopy. Most transfusions were administered at a time at which the patient did not appear to be oxygen delivery dependent according to global measures of tissue oxygenation. PMID- 25137552 TI - Time to reappraise the use of body mass index in genetic association studies of children? PMID- 25137551 TI - Greater fluctuations in serum sodium levels are associated with increased mortality in children with externalized ventriculostomy drains in a PICU. AB - OBJECTIVES: Dysnatremia is common in critically ill children due to disruption of hormonal homeostasis. Children with brain injury are at risk for syndrome of inappropriate antidiuretic hormone, cerebral salt wasting, and sodium losses due to externalized ventricular drain placement. We hypothesized that among PICU patients managed with an externalized ventricular drain, hyponatremia is common, hyponatremia is associated with seizures and in-hospital mortality, and greater sodium fluctuations are associated with in-hospital mortality. DESIGN: Retrospective observational study. SETTING: Tertiary care PICU. PATIENTS: All pediatric patients treated in the PICU with an externalized ventricular drain from January 2005 to December 2009. Patients were identified by searching the physician order entry database for externalized ventricular drain orders. Hyponatremia was defined as the minimum sodium during patients' externalized ventricular drain time and was categorized as mild (131-134 mEq/L) or moderate to severe (<= 130 mEq/L). Magnitude of sodium fluctuation was defined as the difference between a patient's highest and lowest sodium during the time in which an externalized ventricular drain was in use (up to 14 d). Seizure was defined as a clinically evident convulsion during externalized ventricular drain presence. A priori confounders were age, history of epilepsy, and externalized ventricular drain indication. Multivariable regression was performed to test the association between sodium derangements and outcomes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three hundred eighty patients were eligible. One hundred nine (29%) had mild hyponatremia, and 30 (8%) had moderate to severe hyponatremia. Twenty eight patients (7%) had a seizure while hospitalized. Eighteen patients died (5%) prior to discharge. Survivors had a median daily sodium fluctuation of 1 mEq/L [0 5] vs non-survivors 9 mEq/L [6-11] (p < 0.001) and a median sodium fluctuation of 5 mEq/L [2-8] vs non-survivors 15 mEq/L [9-24] (p < 0.001) during externalized ventricular drain management. After controlling for a priori covariates and potential confounders, hyponatremia was not associated with an increased odds of seizures or in-hospital mortality. However, greater fluctuations in daily sodium (odds ratio, 1.38; 95% CI, 1.06-1.8) and greater fluctuations in sodium during externalized ventricular drain management were associated with increased odds of in-hospital mortality (odds ratio, 1.59; 95% CI, 1.2-2.11). CONCLUSIONS: Hyponatremia was common in PICU patients treated with externalized ventricular drains but not associated with seizures or in-hospital mortality. Greater sodium fluctuations during externalized ventricular drain management were independently associated with increased odds of in-hospital mortality. PMID- 25137553 TI - Improving the oral health of residents with intellectual and developmental disabilities: an oral health strategy and pilot study. AB - This article presents an oral health (OH) strategy and pilot study focusing on individuals with intellectual and/or developmental disabilities (IDD) living in group homes. The strategy consists of four components: (1) planned action in the form of the behavioral contract and caregiver OH action planning; (2) capacity building through didactic and observation learning training; (3) environmental adaptations consisting of additional oral heath devices and strategies to create a calm atmosphere; and (4) reinforcement by post-training coaching. A pilot study was conducted consisting of pre- and post-assessment data collected 1 week before and 1 week after implementing a 1-month OH strategy. The study sample comprised 11 group homes with 21 caregivers and 25 residents with IDD from one service organization in a Midwestern city. A process evaluation found high-quality implementation of the OH strategy as measured by dosage, fidelity, and caregiver reactions to implementing the strategy. Using repeated cross-sectional and repeated measures analyses, we found statistically significant positive changes in OH status and oral hygiene practices of residents. Caregiver self-efficacy as a mechanism of change was not adequately evaluated; however, positive change was found in some but not all types of caregiver OH support that were assessed. Lessons learned from implementing the pilot study intervention and evaluation are discussed, as are the next steps in conducting an efficacy study of the OH strategy. PMID- 25137555 TI - Photocontrolled nanoparticle delivery systems for biomedical applications. AB - "Smart" stimuli-responsive nanomaterials are becoming popular as targeted delivery systems because they allow the use of internal or external stimuli to achieve spatial or temporal control over the delivery process. Among the stimuli that have been used, light is of special interest because it is not only noninvasive but also controllable both spatially and temporally, thus allowing unprecedented control over the delivery of bioactive molecules such as nucleic acids, proteins, drugs, etc. This is particularly advantageous for biomedical applications where specificity and selectivity are highly desired. Several strategies have evolved under the umbrella of light based delivery systems and can be classified into three main groups. The first strategy involves "caging" of the bioactive molecule using photolabile groups, loading these caged molecules onto a carrier and then "uncaging" or activating them at the targeted site upon irradiation with light of a particular wavelength. The second strategy makes use of nanocarriers that themselves are made photoresponsive either through modification with photosensitive groups or through the attachment of photolinkers on the carrier surface. These nanoparticles upon irradiation dissociate, releasing the cargo encapsulated within, or the photolinkers attaching the cargo to the surface get cleaved, resulting in release. The third approach makes use of the surface plasmon resonance of noble metal based nanoparticles. Upon irradiation with light at the plasmon resonant frequency, the resulting thermal or nonthermal field enhancement effects facilitate the release of bioactive molecules loaded onto the nanoparticles. In addition, other materials, certain metal sulfides, graphene oxide, etc., also exhibit photothermal transduction that can be exploited for targeted delivery. These approaches, though effective, are constrained by their predominant use of UV or visible light to which most photolabile groups are sensitive. Near infrared (NIR) excitation is preferred because NIR light is safer and can penetrate deeper in biological tissues. However, most photolabile groups cannot be excited by NIR light directly. So light conversion from NIR to UV/visible is required. Nanomaterials that display upconversion or two-photon-excitation properties have been developed that can serve as nanotransducers, converting NIR to UV/visible light to which the aforementioned photoresponsive moieties are sensitive. This Account will review the existing light-based nanoparticle delivery systems, their applications, the limitations they face, and the technologies that have emerged in an effort to overcome these limitations. PMID- 25137554 TI - Plasmonic library based on substrate-supported gradiential plasmonic arrays. AB - We present a versatile approach to produce macroscopic, substrate-supported arrays of plasmonic nanoparticles with well-defined interparticle spacing and a continuous particle size gradient. The arrays thus present a "plasmonic library" of locally noncoupling plasmonic particles of different sizes, which can serve as a platform for future combinatorial screening of size effects. The structures were prepared by substrate assembly of gold-core/poly(N-isopropylacrylamide) shell particles and subsequent post-modification. Coupling of the localized surface plasmon resonance (LSPR) could be avoided since the polymer shell separates the encapsulated gold cores. To produce a particle array with a broad range of well-defined but laterally distinguishable particle sizes, the substrate was dip-coated in a growth solution, which resulted in an overgrowth of the gold cores controlled by the local exposure time. The kinetics was quantitatively analyzed and found to be diffusion rate controlled, allowing for precise tuning of particle size by adjusting the withdrawal speed. We determined the kinetics of the overgrowth process, investigated the LSPRs along the gradient by UV-vis extinction spectroscopy, and compared the spectroscopic results to the predictions from Mie theory, indicating the absence of local interparticle coupling. We finally discuss potential applications of these substrate-supported plasmonic particle libraries and perspectives toward extending the concept from size to composition variation and screening of plasmonic coupling effects. PMID- 25137557 TI - Analyzing and grading effectiveness research: a new approach. PMID- 25137556 TI - Association between ambient noise exposure, hearing acuity, and risk of acute occupational injury. AB - OBJECTIVE: This study aimed to examine the associations between acute workplace injury risk, ambient noise exposure, and hearing acuity, adjusting for reported hearing protection use. METHODS: In a cohort of 9220 aluminum manufacturing workers studied over six years (33 300 person-years, 13 323 person-jobs), multivariate mixed effects models were used to estimate relative risk (RR) of all injuries as well as serious injuries by noise exposure category and hearing threshold level (HTL) adjusting for recognized and potential confounders. RESULTS: Compared to noise <82 dBA, higher exposure was associated with elevated risk in a monotonic and statistically significant exposure-response pattern for all injuries and serious injuries with higher risk estimates observed for serious injuries [82-84.99 dBA: RR 1.26, 95% confidence interval (95% CI) 0.96-1.64; 85 87.99 dBA: RR 1.39, 95% CI 1.05-1.85; >=88 dBA: RR 2.29, 95% CI 1.52-3.47]. Hearing loss was associated with increased risk for all injuries, but was not a significant predictor of risk for the subset of more serious injuries. Compared to those without hearing loss, workers with HTL >=25 dB had 21% increased all injury risk (RR 1.21, 95% CI 1.09-1.33) while those with HTL 10-24.99 dB had 6% increased risk (RR 1.06, 95% CI 1.00-1.13). Reported hearing protection type did not predict injury risk. CONCLUSION: Noise exposure levels as low as 85 dBA may increase workplace injury risk. HTL was associated with increased risk for all, but not the subset of serious, injuries. Additional study is needed both to confirm the observed associations and explore causal pathways. PMID- 25137558 TI - Transplantation: recognizing self versus non-self: new territory for monocytes. PMID- 25137561 TI - Development: Wnt5a implicated in CAKUT. PMID- 25137565 TI - Effect of calcium-ozone treatment on chemical and biological properties of polyethylene terephthalate. AB - Ozone (O3 ) treatment of polyethylene terephthalate (PET) in distilled water was performed in the presence and absence of calcium (Ca(2+) ). PET was oxidized and thus carboxylic and hydroxyl functional groups were introduced on its surface after O3 treatment, regardless of the presence or absence of Ca(2+) . In the case of O3 treatment with Ca(2+) , PET surface was modified with Ca(2+) . Ca(2+) immobilization was confirmed by X-ray photoelectron spectrometric analysis. Hydrophilicity was investigated by measuring contact angles (CA). CA of PET decreased significantly after ozonation. Surface topography of PET before and after ozone treatment was observed by scanning electron microscopy, and showed no morphological changes. In vitro studies showed enhanced rat bone marrow cell responses on the O3 -treated PET surface. Ca(2+) -O3 oxidation at 37 degrees C for 6 h is expected to be an effective method to fabricate PET with good biocompatibility. PMID- 25137566 TI - Study of the kinetics and mechanism of rapid self-assembly in block copolymer thin films during solvo-microwave annealing. AB - Microwave annealing is an emerging technique for achieving ordered patterns of block copolymer films on substrates. Little is understood about the mechanisms of microphase separation during the microwave annealing process and how it promotes the microphase separation of the blocks. Here, we use controlled power microwave irradiation in the presence of tetrahydrofuran (THF) solvent, to achieve lateral microphase separation in high-chi lamellar-forming poly(styrene-b-lactic acid) PS b-PLA. A highly ordered line pattern was formed within seconds on silicon, germanium and silicon on insulator (SOI) substrates. In-situ temperature measurement of the silicon substrate coupled to condition changes during "solvo microwave" annealing allowed understanding of the processes to be attained. Our results suggest that the substrate has little effect on the ordering process and is essentially microwave transparent but rather, it is direct heating of the polar THF molecules that causes microphase separation. It is postulated that the rapid interaction of THF with microwaves and the resultant temperature increase to 55 degrees C within seconds causes an increase of the vapor pressure of the solvent from 19.8 to 70 kPa. This enriched vapor environment increases the plasticity of both PS and PLA chains and leads to the fast self-assembly kinetics. Comparing the patterns formed on silicon, germanium and silicon on insulator (SOI) and also an in situ temperature measurement of silicon in the oven confirms the significance of the solvent over the role of substrate heating during "solvo-microwave" annealing. Besides the short annealing time which has technological importance, the coherence length is on a micron scale and dewetting is not observed after annealing. The etched pattern (PLA was removed by an Ar/O2 reactive ion etch) was transferred to the underlying silicon substrate fabricating sub-20 nm silicon nanowires over large areas demonstrating that the morphology is consistent both across and through the film. PMID- 25137567 TI - A fluorescent biosensor based on carbon dots-labeled oligodeoxyribonucleotide and graphene oxide for mercury (II) detection. AB - As the newest two members of the carbon materials family, carbon dots (CDs) and graphene oxide (GO) possess many excellent optical properties resulting in a wide range of applications. In this work, we successfully synthesized CDs with a high quantum-yield, and labeled them on oligodeoxyribonucleotide (ODN). The fluorescence of resultant CDs-labeled oligodeoxyribonucleotide (ODN-CDs) was quenched by GO via fluorescence resonance energy transfer. In the presence of Hg(2+), the fluorescence was recovered by the release of ODN-CDs from GO due to the formation of T-Hg(2+)-T duplex. In the light of this theory, we designed a simple, highly sensitive and selective fluorometric Hg(2+) sensor based on CDs labeled oligodeoxyribonucleotide and GO without complicated, costly and time consuming operations. Under the optimal conditions, a linear relationship was obtained between relative fluorescence intensity and the concentration of Hg(2+) in the range of 5-200 nM (R(2)=0.974). The present GO-based sensor system is highly selective toward Hg(2+) over a wide range of metal ions and has a detection limit of 2.6 nM. This method is reliable, and has been successfully applied for the detection of Hg(2+) in practical samples. PMID- 25137568 TI - "That one makes things small": Experimentally induced spontaneous memories in 3.5 year-olds. AB - We introduce a new method for examining spontaneous (unprompted) autobiographical memories in 3.5-year-old children, by inducing them in a laboratory setting. Thirty-eight 3.5-year-olds, who had previously participated in a study in our lab involving highly unique props, were brought back after a one-month delay to the same lab arranged as in the original study and with the same Experimenter present. While waiting for the Experimenter in front of the props, their spontaneous verbalizations about the previous unique experiment were recorded, scored, and compared to those of 29 naive Controls of the same age. The children in the experimental group produced significantly more spontaneous verbalizations related to the to-be-remembered event measured on a variety of dimensions. The study introduces a promising new approach to investigating spontaneous memories in young children in a controlled lab setting. The findings are discussed in relation to involuntary autobiographical memories as examined in adults. PMID- 25137569 TI - Distorted subjective reports of stimulus onsets under dual-task conditions: Delayed conscious perception or estimation bias? AB - We investigated whether selecting a response for one task delays the conscious perception of another stimulus (delayed conscious perception hypothesis). In two experiments, participants watched a revolving clock hand while performing two tasks in close succession (i.e. a dual-task). Two stimuli were presented with varying stimulus onset asynchrony (SOA). After each trial, participants separately estimated the onsets of the two stimuli on the clock face. Across two experiments and four conditions, we manipulated response requirements and assessed their impact on perceived stimulus onsets. Results showed that (a) providing speeded responses to the stimuli did lead to greater SOA-dependent misperceptions of both stimulus onsets as compared to a solely perceptual condition, and (b) that response grouping reduced these misperceptions. Overall, the results provide equivocal evidence for the delayed conscious perception hypothesis. They rather suggest that participants' estimates of the two stimulus onsets are biased by the interval between their responses. PMID- 25137562 TI - Translational research in ADPKD: lessons from animal models. AB - Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2, which encode polycystin-1 and polycystin-2, respectively. Rodent models are available to study the pathogenesis of polycystic kidney disease (PKD) and for preclinical testing of potential therapies-either genetically engineered models carrying mutations in Pkd1 or Pkd2 or models of renal cystic disease that do not have mutations in these genes. The models are characterized by age at onset of disease, rate of disease progression, the affected nephron segment, the number of affected nephrons, synchronized or unsynchronized cyst formation and the extent of fibrosis and inflammation. Mouse models have provided valuable mechanistic insights into the pathogenesis of PKD; for example, mutated Pkd1 or Pkd2 cause renal cysts but additional factors are also required, and the rate of cyst formation is increased in the presence of renal injury. Animal studies have also revealed complex genetic and functional interactions among various genes and proteins associated with PKD. Here, we provide an update on the preclinical models commonly used to study the molecular pathogenesis of ADPKD and test potential therapeutic strategies. Progress made in understanding the pathophysiology of human ADPKD through these animal models is also discussed. PMID- 25137570 TI - Looking at proteins from two dimensions: a review on five decades of 2D electrophoresis. AB - Separating proteins according to two different gel-electrophoretic methods not only increases the resolution power for highly complex samples when compared to one-dimensional separations, but is also a valuable tool for protein and protein complex characterization. There are a number of different electrophoresis methods which can be combined. The combination of isoelectric focusing under denaturing conditions and SDS polyacrylamide gel electrophoresis delivers the highest resolution of all bio-analytic techniques. This is a short review on the history and state of the art of two-dimensional electrophoresis methods, and contains some practical tips for high resolution 2D electrophoresis, which are based on several decades of experience with this method. PMID- 25137572 TI - Singly protonated dehydronorcantharidin silver coordination polymer induces apoptosis of lung cancer cells via reactive oxygen species-mediated mitochondrial pathway. AB - Silver complexes have been shown to possess antimicrobial and anticancer properties. Ag-SP-DNC, a novel silver and singly protonated dehydronorcantharidin complex, was synthesized in our previous study. In this study, we offer evidence that Ag-SP-DNC elicits a reactive oxygen species (ROS)-mediated mitochondrial apoptosis in lung cancer cells. Ag-SP-DNC inhibited the growth of A549 cells by inducing G2/M phase cell cycle arrest and apoptosis. Ag-SP-DNC induced apoptosis was associated with the levels of intracellular ROS. The further study revealed that Ag-SP-DNC disrupted the mitochondrial membrane potential, induced the caspase-3 activation and led to the translocation of apoptosis inducing factor and endonucleaseG to the nucleus. These findings have important implications for the development of silver complexes for anticancer applications. PMID- 25137571 TI - Effects of lateral funiculus sparing, spinal lesion level, and gender on recovery of bladder voiding reflexes and hematuria in rats. AB - Deficits in bladder function are complications following spinal cord injury (SCI), severely affecting quality of life. Normal voiding function requires coordinated contraction of bladder and urethral sphincter muscles dependent upon intact lumbosacral reflex arcs and integration of descending and ascending spinal pathways. We previously reported, in electrophysiological recordings, that segmental reflex circuit neurons in anesthetized male rats were modulated by a bilateral spino-bulbo-spinal pathway in the mid-thoracic lateral funiculus. In the present study, behavioral measures of bladder voiding reflexes and hematuria (hemorrhagic cystitis) were obtained to assess the correlation of plasticity dependent recovery to the degree of lateral funiculus sparing and mid-thoracic lesion level. Adult rats received mid-thoracic-level lesions at one of the following severities: complete spinal transection; bilateral dorsal column lesion; unilateral hemisection; bilateral dorsal hemisection; a bilateral lesion of the lateral funiculi and dorsal columns; or a severe contusion. Voiding function and hematuria were evaluated by determining whether the bladder was areflexic (requiring manual expression, i.e., "crede maneuver"), reflexive (voiding initiated by perineal stroking), or "automatic" (spontaneous voiding without caretaker assistance). Rats with one or both lateral funiculi spared (i.e., bilateral dorsal column lesion or unilateral hemisection) recovered significantly faster than animals with bilateral lateral funiculus lesions, severe contusion, or complete transection. Bladder reflex recovery time was significantly slower the closer a transection lesion was to T10, suggesting that proximity to the segmental sensory and sympathetic innervation of the upper urinary tract (kidney, ureter) should be avoided in the choice of lesion level for SCI studies of micturition pathways. In addition, hematuria duration was significantly longer in males, compared to females, despite similar bladder reflex onset times. We conclude that the sparing of the mid-thoracic lateral funiculus on one side is required for early recovery of bladder reflex voiding function and resolution of hematuria. PMID- 25137573 TI - Pyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase: structure based design, synthesis, SAR and antimicrobial activity. AB - The development of antibacterial drugs based on novel chemotypes is essential to the future management of serious drug resistant infections. We herein report the design, synthesis and SAR of a novel series of N-ethylurea inhibitors based on a pyridine-3-carboxamide scaffold targeting the ATPase sub-unit of DNA gyrase. Consideration of structural aspects of the GyrB ATPase site has aided the development of this series resulting in derivatives that demonstrate excellent enzyme inhibitory activity coupled to potent Gram positive antibacterial efficacy. PMID- 25137574 TI - Isolation and cytotoxic effect of anthraquinones from Morinda umbellata. AB - Four new anthraquinones, 1,6-dihydroxy-2-methoxymethylanthraquinone (1), 6 hydroxy-7-methoxy-2-methoxymethylanthraquinone (3), 3,6-dihydroxy-7-methoxy-2 methylanthraquinone (4), and 6-hydroxy-2-methoxymethylanthraquinone (8), together with 12 known anthraquinones and 6 other known compounds, were isolated from the EtOAc extract of Morinda umbellata. Among the isolated compounds, 1, rubiadin (14), and, 3-hydroxy-2-hydroxymethylanthraquinone (16) exhibited significant cytotoxicities against HepG2 cells, with GI50 values of 4.4, 3.6, and 4.8 uM, respectively. PMID- 25137575 TI - Bioactive sesquiterpene coumarins from Ferula pseudalliacea. AB - One new and five known sesquiterpene coumarins were isolated from the roots of Ferula pseudalliacea. The structures were elucidated by 1D and 2D NMR, and HR ESIMS data as 4'-hydroxy kamolonol acetate (1), kamolonol (2), szowitsiacoumarin A (3), farnesiferon B (4), farnesiferol C (5), and flabellilobin A (6). The absolute configuration of compounds 1, 2, and 4 was established by comparison of experimental and simulated electronic circular dichroism spectra using time dependence density function theory. 4'-Hydroxy kamolonol acetate and kamolonol showed antibacterial activity against Heliobacter pylori and Staphylococcus aureus at a concentration of 64 ug/mL. Kamolonol, 4'-hydroxy kamolonol acetate, and farnesiferon B displayed a cytotoxic activity in HeLa cells, with an IC50 of 3.8, 4.5, and 7.7 uM, respectively. PMID- 25137577 TI - Compromise solutions between conservation and road building in the tropics. AB - Road construction is now common through wilderness and protected areas in tropical and subtropical countries with adverse consequences for their high native biodiversity. Here, we summarize the scope of the problem and advance specific compromise solutions that reconcile development with conservation. PMID- 25137576 TI - Antioxidative activity of diarylheptanoids from the bark of black alder (Alnus glutinosa) and their interaction with anticancer drugs. AB - Diarylheptanoids belong to polyphenols, a group of plant secondary metabolites with multiple biological properties. Many of them display antioxidative, cytotoxic, or anticancer actions and are increasingly recognized as potential therapeutic agents. The aim of this study was to evaluate antioxidant and cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4 hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen species production was examined by dihydroethidium staining. Mitochondrial structure and doxorubicin localization were visualized by fluorescent microscopy. Gene expression of manganese superoxide dismutase and hypoxia-inducible factor 1alpha was determined by reverse transcription polymerase chain reaction. Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin, significantly increasing their IC50 values in normal cells. Diarylheptanoid 1 induced the retention of doxorubicin in cytoplasm and reduced mitochondrial fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced the reactive oxygen species production induced by cisplatin. Both compounds increased the messenger ribonucleic acid expression of enzymes involved in reactive oxygen species elimination (manganese superoxide dismutase and hypoxia inducible factor-1alpha). These results indicate that neutralization of reactive oxygen species is an important mechanism of diarylheptanoid action, although these compounds exert a considerable anticancer effect. Therefore, these compounds may serve as protectors of normal cells during chemotherapy without significantly diminishing the effect of the applied chemotherapeutic. PMID- 25137578 TI - Beaked whales. PMID- 25137579 TI - piRNAs. PMID- 25137580 TI - Multisensory context portends object memory. PMID- 25137581 TI - Touch improvement at the hand transfers to the face. PMID- 25137582 TI - Embodiment of others' hands elicits arousal responses similar to one's own hands. PMID- 25137583 TI - Object perception: where do we see the weight? AB - A new study of the response of the human brain as subjects view objects of different weights they are about to lift shows that the weight of objects, which influences the way we act upon them, is represented in the ventral stream of the visual cortex. PMID- 25137584 TI - Golgi apparatus: finally mechanics comes to play in the secretory pathway. AB - New findings report a mechanical role for actin in Golgi organization and vesicular trafficking. An elegant study uses optical tweezers and live-cell imaging to demonstrate the effects of a mechanical constraint on the dynamics of secretory membrane trafficking, combining physical experimental approaches with in cellulo studies of endomembranes. PMID- 25137585 TI - Behavioral sequencing: competitive queuing in the fly CNS. AB - A study of grooming behaviors in Drosophila suggests a neuronal mechanism for how animals produce complex motor patterns from ordered interactions among modules of different motor acts. This mechanism may be a common one in many nervous systems. PMID- 25137586 TI - Multiciliogenesis: multicilin directs transcriptional activation of centriole formation. AB - During differentiation of multiciliated cells, numerous centrioles are generated in each cell to act as templates for the formation of a corresponding number of cilia. A new study reveals that multicilin, a protein required for multiciliogenesis, is a key component of a regulatory complex that activates the transcription of genes required for centriole formation. PMID- 25137587 TI - Animal behaviour: task differentiation by personality in spider groups. AB - In social animals, group efficiency is often assumed to increase with task differentiation, but this requires that individuals are better than generalists at the task they specialize in. A new study finds that individual Anelosimus studiosus spiders do predominantly perform the task they excel at, in line with their individual personality type, when they are placed in groups. PMID- 25137588 TI - Dinosaur evolution: feathers up for selection. AB - A new specimen of the early bird Archaeopteryx shows remarkable plumage preservation, including pennaceous leg feathers. But whether birds went through a four-winged stage, and in what exact functional context feathers evolved remains a matter of debate. PMID- 25137589 TI - Vision: two plus four equals six. AB - Using two UV-sensitive visual pigments and the UV-filtering properties of four mycosporine-like amino acids, mantis shrimp create six spectrally distinct UV receptors. This is yet another example of the unique ways in which mantis shrimp have adapted to extract information from their visual world. PMID- 25137590 TI - Genetics: finding genes for schizophrenia. AB - New studies have substantially advanced our understanding of the genetic architecture of schizophrenia, but we are far from identifying the underlying mutations. We may require new approaches to understand the biological implications of insights into the genetics of psychiatric disease. PMID- 25137591 TI - Evolution: ctenophore genomes and the origin of neurons. AB - Recent sequencing of ctenophore genomes opens a new era in the study of this unique and phylogenetically distant group. The presence of neurodevelopmental genes, pre- and postsynaptic modules, and transmitter molecules is consistent with a single origin of neurons. PMID- 25137593 TI - Anomalous crystallization as a signature of the fragile-to-strong transition in metallic glass-forming liquids. AB - We study the fragile-to-strong (F-S) transition of metallic glass-forming liquids (MGFLs) by measuring the thermal response during annealing and dynamic heating of La55Al25Ni5Cu15 glass ribbons fabricated at different cooling rates. We find that the glasses fabricated in the intermediate regime of cooling rates (15-25 m/s) exhibit an anomalous crystallization behavior upon reheating as compared to the glasses formed at other cooling rates. This anomalous crystallization behavior implies the existence of a thermodynamic F-S transition, could be used as an alternative method for detecting the F-S transition in MGFLs, and sheds light on the structure origin of the F-S transition. This work also contributes to obtaining a general thermodynamic picture of the F-S transition in supercooled liquids. PMID- 25137594 TI - Research progress in structure-activity relationship of bioactive peptides. AB - Bioactive peptides are specific protein fragments that have positive impact on health. They are important sources of new biomedicine, energy and high performance materials. The beneficial effects of bioactive peptides are due to their antioxidant, antihypertensive, anticarcinogenic, antimicrobial, and immunomodulatory activities. The structure-activity relationship of bioactive peptides plays a significant role in the development of innovative and unconventional synthetic polymeric counterparts. It provides the basis of the stereospecific synthesis, transformation, and development of bioactive peptide products. This review covers the progress of studies in the structure-activity relationship of some bioactive peptides including antioxidant peptides, angiotensin-I-converting enzyme-inhibitory peptides, and anticarcinogenic peptides in the past decade. PMID- 25137595 TI - Mn(II/III) complexes as promising redox mediators in quantum-dot-sensitized solar cells. AB - The advancement of quantum dot sensitized solar cell (QDSSC) technology depends on optimizing directional charge transfer between light absorbing quantum dots, TiO2, and a redox mediator. The nature of the redox mediator plays a pivotal role in determining the photocurrent and photovoltage from the solar cell. Kinetically, reduction of oxidized quantum dots by the redox mediator should be rapid and faster than the back electron transfer between TiO2 and oxidized quantum dots to maintain photocurrent. Thermodynamically, the reduction potential of the redox mediator should be sufficiently positive to provide high photovoltages. To satisfy both criteria and enhance power conversion efficiencies, we introduced charge transfer spin-crossover Mn(II/III) complexes as promising redox mediator alternatives in QDSSCs. High photovoltages ~ 1 V were achieved by a series of Mn poly(pyrazolyl)borates, with reduction potentials ~ 0.51 V vs Ag/AgCl. Back electron transfer (recombination) rates were slower than Co(bpy)3, where bpy = 2,2'-bipyridine, evidenced by electron lifetimes up to 4 orders of magnitude longer. This is indicative of a large barrier to electron transport imposed by spin-crossover in these complexes. Low solubility prevented the redox mediators from sustaining high photocurrent due to mass transport limits. However, with high fill factors (~ 0.6) and photovoltages, they demonstrate competitive efficiencies with Co(bpy)3 redox mediator at the same concentration. More positive reduction potentials and slower recombination rates compared to current redox mediators establish the viability of Mn poly(pyrazolyl)borates as promising redox mediators. By capitalizing on these characteristics, efficient Mn(II/III)-based QDSSCs can be achieved with more soluble Mn-complexes. PMID- 25137596 TI - Writing an abstract to sell your scholarly work. PMID- 25137592 TI - Aberrant regulation and function of microRNAs in cancer. AB - Malignant neoplasms are consistently among the top four leading causes of death in all age groups in the United States, despite a concerted effort toward developing novel therapeutic approaches. Our understanding of and therapeutic strategy for treating each of these neoplastic diseases have been improved through decades of research on the genetics, signaling pathways, and cellular biology that govern tumor cell initiation, progression and maintenance. Much of this work has concentrated on post-translational modifications and abnormalities at the DNA level, including point mutations, amplifications/deletions, and chromosomal translocations, and how these aberrant events affect the expression and function of protein-coding genes. Only recently has a novel class of conserved gene regulatory molecules been identified as a major contributor to malignant neoplastic disease. This review focuses on how these small non-coding RNA molecules, termed microRNAs (miRNAs), can function as oncogenes or tumor suppressors, and how the misexpression of miRNAs and dysregulation of factors that regulate miRNAs contribute to the tumorigenic process. Specific focus is given to more recently discovered regulatory mechanisms that go awry in cancer, and how these changes alter miRNA expression, processing, and function. PMID- 25137600 TI - Wolf-Hirschhorn syndrome: a case study and disease overview. AB - Wolf-Hirschhorn syndrome is caused by a deletion of a segment on the short arm (p) of chromosome 4. The major features of this disorder include a characteristic facial appearance known as the "Greek helmet," delayed growth and development; prenatally and postnatally, intellectual disabilities, and seizures. To provide comprehensive and appropriate nursing and medical care to infants with Wolf Hirschhorn syndrome, it is imperative to know and understand the disorder. A case study of a 36 weeks' gestational age white-Hispanic male infant with Wolf Hirschhorn syndrome is presented with the purpose of increasing clinical knowledge and the implications for the clinical nurse and neonatal nurse practitioner. PMID- 25137602 TI - What opportunities does NANN provide to support evidence-based practice and research? PMID- 25137601 TI - The neonatal nurse's role in preventing abusive head trauma. AB - Abusive head trauma in infants occurs in 24.6 to 39.8 per 100,000 infants in developed countries. Abusive head trauma refers to any type of intentional head trauma an infant sustains, as a result of an injury to the skull or intracranial contents from a blunt force and/or violent shaking. The clinical question was: what evidence-based interventions have been implemented by neonatal nurses to prevent abusive head trauma in infants? PubMed was searched to obtain English language publications from 2005 to May 2014 for interventions focused on preventing abusive head trauma using the key term "shaken baby syndrome." A total of 10 studies were identified that met the inclusion criteria. All of the interventions targeted prevention of abusive head trauma with information about abusive head trauma/shaken baby syndrome and the "normal" infant crying behaviors. Interventions taught parents why infants cried, how to calm the infants, ways to cope with inconsolable infants, and how to develop a plan for what to do if they could not cope anymore. Parents who participated in the interventions were consistently able to explain the information and tell others about the dangers of shaking infants compared to the control parents. Only 2 studies calculated the preintervention abusive head trauma rate and the postintervention frequency of abusive head trauma. Each found significant differences in abusive head trauma. PMID- 25137603 TI - Hemorrhagic Hairy Polyp Causing Velopharyngeal Dysfunction in a Newborn. AB - Velopharyngeal dysfunction (VPD) can be secondary to anatomic, neurologic, or functional maldevelopment in the pediatric population. We present a case of transient VPD after the removal of a voluminous oropharyngeal hairy polyp in a newborn with an intact palate. This report sensitizes physicians, speech-language pathologists, and occupational therapists not only to the repercussions of oropharyngeal congenital masses, such as hairy polyps, on the feeding mechanisms of a newborn but also to the possibility of conservative management. PMID- 25137604 TI - Clinical Factors Affecting Length of Stay After 100 Consecutive Cases of Primary Cleft Lip Repair. AB - OBJECTIVE: To analyze the hospital course of 100 consecutive infants after primary cleft lip repair (PCLR) and identify factors related to length of stay (LOS). DESIGN: Retrospective analysis of 100 consecutive infants who were routinely admitted after PCLR. SETTING: Tertiary care center. PATIENTS: One hundred consecutive infants undergoing PCLR. Demographic and perioperative data were collected and analyzed. MAIN OUTCOME MEASURE: LOS, planned before data collection. RESULTS: Male:female ratio was 65:35. Seventy-two infants had unilateral cleft lip; syndromic association was documented in 15 patients. Mean age and weight at PCLR were 5.6 +/- 4.0 months and 6.7 +/- 1.3 kg, respectively. Mean duration of surgery was 2.5 +/- 0.9 hours, and mean duration of general anesthesia was 3.4 +/- 0.9 hours. A total of 3.3 +/- 1.5 mL of intraoperative local anesthetic was used per patient. Intravenous fluids were necessary after transfer from the post-anesthesia care unit to the general ward in 98% of patients. Almost half (44%) of all patients received intravenous morphine 23 hours or more after hospital admission. Mean LOS was 35.8 +/- 13.9 hours. No association was identified between patient demographic factors and LOS. Multivariate linear regression models identified significant positive correlation between LOS and duration of general anesthesia (P = .002). Greater volume of postoperative oral intake (P = .000) and higher acetaminophen dosage on the floor (P = .000) correlated with decreased LOS. CONCLUSIONS: This study identifies perioperative factors associated with LOS. Our findings question the safety of routine outpatient or short-stay observation after PCLR. PMID- 25137605 TI - High risk of adult asthma following severe wheezing in early life. AB - BACKGROUND: Severe wheezing in early life is associated with an increased risk of asthma during childhood and adolescence. The aim of the present follow-up was to investigate the asthma prevalence and risk factors for asthma in adulthood. METHODS: We have prospectively studied asthma development in 101 children hospitalized due to severe wheezing before the age of 24 months. The cohort was re-investigated at a mean age of 27 years and tested for bronchial hyper responsiveness and allergic sensitization. The response rate in adulthood was 81% (82/101). The results were compared with a population-based, age-matched control group (n = 1,210) recruited from the West Sweden Asthma Study. RESULTS: Current doctor-diagnosed asthma was found in 37% (30/82) compared with 7% (82/1,210) in the control group. The risk of adult asthma in the cohort compared with the control group was increased 10-fold (adjusted OR 10.0, 95% CI 5.3-18.7), independently of allergic rhinitis, gender, smoking and heredity. Within the cohort, current allergy (aOR 9.6, 95% CI 3.0-31.2) and female gender (aOR 3.2, 95% CI 1.1-9.3) independently increased the risk of adult asthma. Females with current allergy had the highest risk of adult asthma (OR 29.4, 95% CI 5.0-173.3), compared with males without allergy. When separately adjusting for factors present at admission in early life within the cohort, a family history of asthma was a significant risk factor for asthma in adulthood (aOR 4.0, 95% CI 1.3-12.5). CONCLUSION: Subjects with severe early wheezing have a 10-fold increase in the risk of adult asthma compared to an age-matched control group, adjusted for allergic rhinitis, gender, smoking and heredity. PMID- 25137606 TI - Determination of glyphosate and aminomethylphosphonic acid in aqueous soil matrices: a critical analysis of the 9-fluorenylmethyl chloroformate derivatization reaction and application to adsorption studies. AB - The assessment of the environmental fate of glyphosate and its degradation product (aminomethylphosphonic acid) is of great interest given the widespread use of the herbicide. Studies of adsorption-desorption and transport processes in soils require analytical methods with sensitivity, accuracy, and precision suitable for determining the analytes in aqueous equilibrium solutions of varied complexity. In this work, the effect of factors on the yield of the derivatization of both compounds with 9-fluorenylmethyl chloroformate for applying in aqueous solutions derived from soils was evaluated through factorial experimental designs. Interference effects coming from background electrolytes and soil matrices were established. The whole method had a linear response up to 640 ng/mL (R(2) > 0.999) under optimized conditions for high-performance liquid chromatography with fluorescence detection. Limits of detection were 0.6 and 0.4 ng/mL for glyphosate and aminomethylphosphonic acid, respectively. The relative standard deviation was 4.4% for glyphosate (20 ng/mL) and 5.9% for aminomethylphosphonic acid (10 ng/mL). Adsorption of compounds on four different soils was assessed. Isotherm data fitted well the Freundlich model (R(2) > 0.97). Kf constants varied between 93 +/- 3.1 and 2045 +/- 157 for glyphosate and between 99 +/- 4.1 and 1517 +/- 56 (MUg(1-1/) (n) mL(1/) (n) ( ) g(-1) ) for aminomethylphosphonic acid, showing the broad range of applicability of the proposed method. PMID- 25137612 TI - Collagen and related extracellular matrix proteins in atherosclerotic plaque development. AB - PURPOSE OF REVIEW: The structure, composition and turnover of the extracellular matrix (ECM) as well as cell-matrix interactions are crucial in the developing atherosclerotic plaque. There is a need for further insight into specific proteins in the ECM and their functions in the developing plaque, and during the last few years a number of publications have highlighted this very important field of research. These novel findings will be addressed in the present review. RECENT FINDINGS: This review covers literature focused on collagen and ECM proteins interacting with collagen, and what their roles may be in plaque development. SUMMARY: Acute myocardial infarction and stroke are common diseases that cause disability and mortality, and the underlying mechanism is often the rupture of a vulnerable atherosclerotic plaque. The vascular ECM and the tissue repair in the atherosclerotic lesion are important players in plaque progression. Understanding how specific proteins in the ECM interact with cells in the plaque and affect the fate of the plaque can lead to new treatments for cardiovascular disease. PMID- 25137613 TI - Electrochemical determination of the density of states of nanostructured NiO films. AB - Mesoporous p-type NiO films were prepared by aerosol-assisted chemical vapor deposition (AACVD) and characterized by X-ray diffraction (XRD). The nanostructure of the films was investigated by field emission gun scanning electron microscopy (FEG-SEM). The density of states (DOS) in these nanostructured films has been determined by means of electrochemical impedance spectroscopy and cyclic voltammetry. The analysis reveals an exponential distribution of band gap states above the valence band that extends around 1.5 eV. In addition, monoenergetic states were also identified which overlap with the exponential distribution. This distribution of states has an enormous influence in the electronic processes of the devices in which NiO electrodes are employed (electrochromism, water splitting or energy storage). Especially, in p-type dye sensitized solar cells (p-DSCs), it is thought that intra-band-gap states are responsible for the fast observed recombination processes, whose existence and distribution has not been clearly determined yet and are now confirmed and quantified by our analysis. This provides a better comprehension of the recombination events which represent one of the main losses in p-DSCs. PMID- 25137614 TI - Does hindered transport theory apply to desalination membranes? AB - As reverse osmosis (RO) and nanofiltration polyamide membranes become increasingly used for water purification, prediction of pollutant transport is required for membrane development and process engineering. Many popular models use hindered transport theory (HTT), which considers a spherical solute moving through an array of fluid-filled rigid cylindrical pores. Experiments and molecular dynamic simulations, however, reveal that polyamide membranes have a distinctly different structure of a "molecular sponge", a network of randomly connected voids widely distributed in size. In view of this disagreement, this study critically examined the validity of HTT by directly measuring diffusivities of several alcohols within a polyamide film of commercial RO membrane using attenuated total reflection-FTIR. It is found that measured diffusivities deviate from HTT predictions by as much as 2-3 orders of magnitude. This result indicates that HTT does not adequately describe solute transport in desalination membranes. As a more adequate alternative, the concept of random resistor networks is suggested, with resistances described by models of activated transport in "soft" polymers without a sharp size cutoff and with a proper address of solute partitioning. PMID- 25137615 TI - Generalized workflow for generating highly predictive in silico off-target activity models. AB - Chemical structure data and corresponding measured bioactivities of compounds are nowadays easily available from public and commercial databases. However, these databases contain heterogeneous data from different laboratories determined under different protocols and, in addition, sometimes even erroneous entries. In this study, we evaluated the use of data from bioactivity databases for the generation of high quality in silico models for off-target mediated toxicity as a decision support in early drug discovery and crop-protection research. We chose human acetylcholinesterase (hAChE) inhibition as an exemplary end point for our case study. A standardized and thorough quality management routine for input data consisting of more than 2,200 chemical entities from bioactivity databases was established. This procedure finally enables the development of predictive QSAR models based on heterogeneous in vitro data from multiple laboratories. An extended applicability domain approach was used, and regression results were refined by an error estimation routine. Subsequent classification augmented by special consideration of borderline candidates leads to high accuracies in external validation achieving correct predictive classification of 96%. The standardized process described herein is implemented as a (semi)automated workflow and thus easily transferable to other off-targets and assay readouts. PMID- 25137616 TI - Prevalence and Characteristics of Chemical Intolerance: A Japanese Population Based Study. AB - Population-based cross-sectional study was performed to estimate the prevalence of chemical intolerance and to examine the characteristics of the sample. A Web based survey was conducted that included 7,245 adults in Japan. The criteria for chemical intolerance proposed by Skovbjerg yielded a prevalence of 7.5% that was approximately consistent with that reported from a Danish population-based survey. Female gender, older age, and renovation in the house during the past 7 years were positively associated with chemical intolerance. Improvements in the condition were observed with daily ventilation habits. Medical history of atopic dermatitis, allergic rhinitis, food allergy, multiple chemical sensitivity, and depression were associated with chemical intolerance. Fatigue, depressed mood, and somatic symptoms were also positively correlated with chemical intolerance. Better elucidation of the causes, comorbidities, concomitants, and consequences of chemical intolerance has the potential to provide effective solutions for its prevention and treatment. PMID- 25137617 TI - Workplace psychosocial factors associated with hypertension in the U.S. workforce: a cross-sectional study based on the 2010 national health interview survey. AB - OBJECTIVE: To explore associations between self-reported hypertension and workplace psychosocial factors that are common among U.S. workers and to identify industries and occupations (I&Os) that are associated with a high prevalence of hypertension, even after adjustment for common known risk factors. METHODS: Data from the 2010 National Health Interview Survey were used to examine relationships between the prevalence of self-reported hypertension and job insecurity, hostile work environment, work- family imbalance, work hours and I&O. RESULTS: Job insecurity (adjusted prevalence ratio (aPR): 1.11; 95% confidence interval (CI): 1.04-1.19)) and hostile work environment (aPR: 1.15; 95% CI: 1.03-1.29) were significantly associated with hypertension. Hypertension prevalence was significantly elevated among those employed in Healthcare Support occupations and Public Administration industries. CONCLUSION: Addressing hostile work environments and the stress associated with job insecurity may improve workers' health. Other occupational factors that contribute to the variation in prevalence of hypertension by I&O should be sought. PMID- 25137618 TI - Comparison of duplex stabilizing properties of 2'-fluorinated nucleic acid analogues with furanose and non-furanose sugar rings. AB - We compare the duplex stabilizing properties of 2'-fluorinated nucleic acid analogues with furanose and non-furanose ring systems and dissect the relative contributions of hydration, sugar conformation, and fluorine configuration toward the overall T(m) value. We find that the stabilization imparted by fluorine substitution is additive over that obtained by restricting the conformation of the sugar ring itself. Our studies support further evaluation of fluorinated nucleic acid analogues with non-furanose sugar rings as surrogates of 2'-F RNA for therapeutic antisense applications. PMID- 25137620 TI - Organophosphorus pesticide chlorpyrifos and its metabolites alter the expression of biomarker genes of differentiation in D3 mouse embryonic stem cells in a comparable way to other model neurodevelopmental toxicants. AB - There are discrepancies about whether chlorpyrifos is able to induce neurodevelopmental toxicity or not. We previously reported alterations in the pattern of expression of biomarker genes of differentiation in D3 mouse embryonic stem cells caused by chlorpyrifos and its metabolites chlorpyrifos-oxon and 3,5,6 trichloro-2-pyridinol. Now, we reanalyze these data comparing the effects on these genes with those caused in the same genes by retinoic acid, valproic acid, and penicillin-G (model compounds considered as strong, weak, and non neurodevelopmental toxicants, respectively). We also compare the effects of chlorpyrifos and its metabolites on the cell viability of D3 cells and 3T3 mouse fibroblasts with the effects caused in the same cells by the three model compounds. We conclude that chlorpyrifos and its metabolites act, regarding these end-points, as the weak neurodevelopmental toxicant valproic acid, and consequently, a principle of caution should be applied avoiding occupational exposures in pregnant women. A second independent experiment run with different cellular batches coming from the same clone obtained the same result as the first one. PMID- 25137619 TI - Propylene cross-bridged macrocyclic bifunctional chelator: a new design for facile bioconjugation and robust (64)Cu complex stability. AB - The first macrocyclic bifunctional chelator incorporating propylene cross-bridge was efficiently synthesized from cyclam in seven steps. After the introduction of an extra functional group for facile conjugation onto the propylene cross-bridge, the two carboxylic acid pendants could contribute to strong coordination of Cu(II) ions, leading to a robust Cu complex. The cyclic RGD peptide conjugate of PCB-TE2A-NCS was prepared and successfully radiolabeled with (64)Cu ion. The radiolabeled peptide conjugate was evaluated in vivo through a biodistribution study and animal PET imaging to demonstrate high tumor uptake with low background. PMID- 25137621 TI - The clinical utility of vocal dosimetry for assessing voice rest. AB - OBJECTIVES/HYPOTHESIS: Voice rest is frequently recommended following surgical disruption of vocal fold epithelium, but patients report variable adherence to voice rest recommendations. The objective of this study was to assess the clinical utility of an ambulatory vocal dosimeter for measuring adherence to voice rest recommendations. STUDY DESIGN: Outcomes research. METHODS: Part 1: To determine the utility of the dosimeter in nonclinical use, the relationship between self-reported voice use and dosimeter measurements was examined in normal subjects (n = 11) who prospectively logged voice use while wearing the dosimeter. Part 2: To determine clinical utility of the dosimeter, patients undergoing vocal fold surgery for which postoperative voice rest was recommended (n = 11) wore a dosimeter for 2 days prior to and 2 days after surgery. Phonation percent and sound level were compared at baseline and during voice rest. RESULTS: The dosimeter performed as hypothesized with both normal subjects and patients. A moderate correlation (r = 0.62) was noted between self-reported voice use and dosimeter measurements in normal subjects. In patients on voice rest, a statistically and clinically significant decrease was observed in measured voice use, both in phonation time (P = .002) and intensity of phonation (P = .004). CONCLUSIONS: Ambulatory vocal dosimetry may have clinical utility for assessing adherence to voice rest recommendations. This information will be useful for the design of future studies on voice rest. PMID- 25137623 TI - Plasmon enhanced terahertz emission from single layer graphene. AB - We show that surface plasmons, excited with femtosecond laser pulses on continuous or discontinuous gold substrates, strongly enhance the generation and emission of ultrashort, broadband terahertz pulses from single layer graphene. Without surface plasmon excitation, for graphene on glass, 'nonresonant laser pulse-induced photon drag currents' appear to be responsible for the relatively weak emission of both s- and p-polarized terahertz pulses. For graphene on a discontinuous layer of gold, only the emission of the p-polarized terahertz electric field is enhanced, whereas the s-polarized component remains largely unaffected, suggesting the presence of an additional terahertz generation mechanism. We argue that in the latter case, 'surface-plasmon-enhanced optical rectification', made possible by the lack of inversion symmetry at the graphene on gold surface, is responsible for the strongly enhanced emission. The enhancement occurs because the electric field of surface plasmons is localized and enhanced where the graphene is located: at the surface of the metal. We believe that our results point the way to small, thin, and more efficient terahertz photonic devices. PMID- 25137622 TI - Morquio A syndrome-associated mutations: a review of alterations in the GALNS gene and a new locus-specific database. AB - Morquio A syndrome (mucopolysaccharidosis IVA) is an autosomal recessive disorder that results from deficient activity of the enzyme N-acetylgalactosamine-6 sulfatase (GALNS) due to alterations in the GALNS gene, which causes major skeletal and connective tissue abnormalities and effects on multiple organ systems. The GALNS alterations associated with Morquio A are numerous and heterogeneous, and new alterations are continuously identified. To aid detection and interpretation of GALNS alterations, from previously published research, we provide a comprehensive and up-to-date listing of 277 unique GALNS alterations associated with Morquio A identified from 1,091 published GALNS alleles. In agreement with previous findings, most reported GALNS alterations are missense changes and even the most frequent alterations are relatively uncommon. We found that 48% of patients are assessed as homozygous for a GALNS alteration, 39% are assessed as heterozygous for two identified GALNS alterations, and in 13% of patients only one GALNS alteration is detected. We report here the creation of a locus-specific database for the GALNS gene (http://galns.mutdb.org/) that catalogs all reported alterations in GALNS to date. We highlight the challenges both in alteration detection and genotype-phenotype interpretation caused in part by the heterogeneity of GALNS alterations and provide recommendations for molecular testing of GALNS. PMID- 25137625 TI - Response to "are the results likely biased toward the null?". PMID- 25137626 TI - N-doped graphene: an alternative carbon-based matrix for highly efficient detection of small molecules by negative ion MALDI-TOF MS. AB - Gas-phase N-doped graphene (gNG) was synthesized by a modified thermal annealing method using gaseous melamine as nitrogen source and then for the first time applied as a matrix in negative ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for small molecule analysis. Unlike the complicated adducts produced in positive ion mode, MS spectra obtained on gNG matrix in negative ion mode was only featured by deprotonated molecule ion peaks without matrix interference. By the gNG assisted desorption/ionization (D/I) process, some applications were carried out on a wide range of low molecular weight (MW) analytes including amino acids, fatty acids, peptides, anabolic androgenic steroids as well as anticancer drugs, with an extraordinary laser desorption/ionization (LDI) efficiency over traditional alpha-cyano-4 hydroxycinnamic acid (CHCA) and other carbon-based materials in the negative ion detection mode. By comparison of a series of graphene-based matrixes, two main factors of matrix gNG were unveiled to play a decisive role in assisting negative ion D/I process: a well-ordered pi-conjugated system for laser absorption and energy transfer; pyridinic-doped nitrogen species functioning as deprotonation sites for proton capture on negative ionization. The good salt tolerance and high sensitivity allowed further therapeutic monitoring of anticancer drug nilotinib in the spiked human serum, a real case of biology. Signal response was definitely obtained between 1 mM and 1 MUM, meeting the demand of assessing drug level in the patient serum. This work creates a new application branch for nitrogen-doped graphene and provides an alternative solution for small molecule analysis. PMID- 25137627 TI - Effective ion mobility calculations for macromolecules by scattering on electron clouds. AB - Broad commercialization and increasing resolving power of ion mobility spectrometry/mass spectrometry (IMS/MS) platforms have engendered an explosion of IMS applications to structural characterization of gas-phase biomolecules. That has renewed interest in more accurate and rapid ion mobility calculations that are needed to elicit ion geometries from the measurements. An approach based on scattering on electron density isosurfaces (SEDI) that mirrors the physics of molecular collisions was proven superior to the common methods involving atomic coordinates a decade ago but has remained impractical for large ions because of extreme computational demands. Here, we accelerate SEDI by up to ~500 times using the fragment molecular orbital approach for surface generation and the multiplexed scattering algorithm in conjunction with the new grid extrapolation procedure for cross section evaluations. Parallelization of the code on a supercomputer has produced major further speed gains, allowing SEDI calculations for proteins (defined by over a million surface points) with a precision of <0.1% in 1 min. Initial tests reveal the anticipated dependence of mobility on the ion charge state and lower cross sections in view of reduced surface roughness. Present developments are expected to lead to broad application of SEDI in IMS studies of macromolecules, enabling more accurate and reliable structural assignments. PMID- 25137624 TI - A proposal for assessing study quality: Biomonitoring, Environmental Epidemiology, and Short-lived Chemicals (BEES-C) instrument. AB - The quality of exposure assessment is a major determinant of the overall quality of any environmental epidemiology study. The use of biomonitoring as a tool for assessing exposure to ubiquitous chemicals with short physiologic half-lives began relatively recently. These chemicals present several challenges, including their presence in analytical laboratories and sampling equipment, difficulty in establishing temporal order in cross-sectional studies, short- and long-term variability in exposures and biomarker concentrations, and a paucity of information on the number of measurements required for proper exposure classification. To date, the scientific community has not developed a set of systematic guidelines for designing, implementing and interpreting studies of short-lived chemicals that use biomonitoring as the exposure metric or for evaluating the quality of this type of research for WOE assessments or for peer review of grants or publications. We describe key issues that affect epidemiology studies using biomonitoring data on short-lived chemicals and propose a systematic instrument--the Biomonitoring, Environmental Epidemiology, and Short lived Chemicals (BEES-C) instrument--for evaluating the quality of research proposals and studies that incorporate biomonitoring data on short-lived chemicals. Quality criteria for three areas considered fundamental to the evaluation of epidemiology studies that include biological measurements of short lived chemicals are described: 1) biomarker selection and measurement, 2) study design and execution, and 3) general epidemiological study design considerations. We recognize that the development of an evaluative tool such as BEES-C is neither simple nor non-controversial. We hope and anticipate that the instrument will initiate further discussion/debate on this topic. PMID- 25137630 TI - Trichomonas vaginalis infections are rare among young patients attending an STI clinic in Sweden. PMID- 25137631 TI - Low-density lipoprotein-mimicking nanoparticles for tumor-targeted theranostic applications. AB - This study introduces multifunctional lipid nanoparticles (LNPs), mimicking the structure and compositions of low-density lipoproteins, for the tumor-targeted co delivery of anti-cancer drugs and superparamagnetic nanocrystals. Paclitaxel (4.7 wt%) and iron oxide nanocrystals (6.8 wt%, 11 nm in diameter) are co-encapsulated within folate-functionalized LNPs, which contain a cluster of nanocrystals with an overall diameter of about 170 nm and a zeta potential of about -40 mV. The folate-functionalized LNPs enable the targeted detection of MCF-7, human breast adenocarcinoma expressing folate receptors, in T2 -weighted magnetic resonance images as well as the efficient intracellular delivery of paclitaxel. Paclitaxel free LNPs show no significant cytotoxicity up to 0.2 mg mL(-1) , indicating the excellent biocompatibility of the LNPs for intracellular drug delivery applications. The targeted anti-tumor activities of the LNPs in a mouse tumor model suggest that the low-density lipoprotein-mimetic LNPs can be an effective theranostic platform with excellent biocompatibility for the tumor-targeted co delivery of various anti-cancer agents. PMID- 25137632 TI - Influence of emulsifier concentration on nanoemulsion gelation. AB - Nanoemulsion gels are a new class of soft materials that manifest stronger elasticity even at lower dispersed phase volume fraction. In this work, gelation in 40 wt % canola oil-in-water nanoemulsions was investigated as a function of emulsifier type (anionic sodium dodecyl sulfate (SDS) or nonionic Tween 20) and concentration. It was observed that the liquid nanoemulsions transformed into viscoelastic gels at a specific concentration range of SDS, whereas no gelation was observed for Tween 20. The apparent viscosity, yield stress, and storage modulus of the nanogels increased with SDS concentration until 15 times critical micelle concentration (CMC), thereafter decreased steadily as the gelation weakened beginning 20 CMC. Three regimes of colloidal interactions in the presence of emulsifier were proposed. (1) Repulsive gelation: at low SDS concentration (0.5-2 times CMC) the repulsive charge cloud around the nanodroplets acted as interfacial shell layer that significantly increased the effective volume fraction of the dispersed phase (phi(eff)). When phi(eff) became comparable to the volume fraction required for maximal random jamming, nanoemulsions formed elastic gels. (2) Attractive gelation: as the SDS concentration increased to 5-15 times CMC, phi(eff) dropped due to charge screening by more counterions from SDS, but depletion attractions generated by micelles in the continuous phase led to extensive droplet aggregation which immobilized the continuous phase leading to stronger gel formation. (3) Decline in gelation due to oscillatory structural forces (OSF): at very high SDS concentration (20-30 time CMC), structural forces were manifested due to the layered-structuring of excess micelles in the interdroplet regions resulting in loss of droplet aggregation. Tween 20 nanoemulsions, on the other hand, did not show repulsive gelation due to lack of charge cloud, while weak depletion attraction and early commencement of OSF regime leading to liquid-like behavior at all concentrations. The nanogels possess great potential for use in low-fat foods, pharmaceuticals and cosmetic products. PMID- 25137633 TI - Riboswitch engineering - making the all-important second and third steps. AB - Synthetic biology uses our understanding of biological systems to develop innovative solutions for challenges in fields as diverse as genetic control and logic devices, bioremediation, materials production or diagnostics and therapy in medicine by designing new biological components. RNA-based elements are key components of these engineered systems. Their structural and functional diversity is ideal for generating regulatory riboswitches that react with many different types of output to molecular and environmental signals. Recent advances have added new sensor and output domains to the existing toolbox, and demonstrated the portability of riboswitches to many different organisms. Improvements in riboswitch design and screens for selecting in vivo active switches provide the means to isolate riboswitches with regulatory properties more like their natural counterparts. PMID- 25137634 TI - Functional characterization of SjB10, an intracellular serpin from Schistosoma japonicum. AB - SUMMARY Serine protease inhibitors (serpin) play essential roles in many organisms. Mammalian serpins regulate the blood coagulation, fibrinolysis, inflammation and complement activation pathways. In parasitic helminths, serpins are less well characterized, but may also be involved in evasion of the host immune response. In this study, a Schistosoma japonicum serpin (SjB10), containing a 1212 bp open reading frame (ORF), was cloned, expressed and functionally characterized. Sequence analysis, comparative modelling and structural-based alignment revealed that SjB10 contains the essential structural motifs and consensus secondary structures of inhibitory serpins. Transcriptional profiling demonstrated that SjB10 is expressed in adult males, schistosomula and eggs but particularly in the cercariae, suggesting a possible role in cercarial penetration of mammalian host skin. Recombinant SjB10 (rSjB10) inhibited pancreatic elastase (PE) in a dose-dependent manner. rSjB10 was recognized strongly by experimentally infected rat sera indicating that native SjB10 is released into host tissue and induces an immune response. By immunochemistry, SjB10 localized in the S. japonicum adult foregut and extra-embryonic layer of the egg. This study provides a comprehensive demonstration of sequence and structural-based analysis of a functional S. japonicum serpin. Furthermore, our findings suggest that SjB10 may be associated with important functional roles in S. japonicum particularly in host-parasite interactions. PMID- 25137629 TI - Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801 induced behavioral impairments and enhances associative learning in rodents. AB - Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for the treatment of psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central nervous system. Prior to this study, the M1 mAChR subtype was viewed as the primary candidate for these actions relative to the other mAChR subtypes. Here we describe the discovery of a novel M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic properties relative to other M4 PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801 induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions, including the touchscreen pairwise visual discrimination task in wild-type mice, but failed to reverse these stimulant induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both contextual and cue-mediated fear conditioning when administered alone in wild type mice. These novel findings suggest that M4 PAMs may provide a strategy for addressing the more complex affective and cognitive disruptions associated with schizophrenia and other neuropsychiatric disorders. PMID- 25137636 TI - Dependency denied: health inequalities in the neo-liberal era. AB - The ways in which inequality generates particular population health outcomes remains a major source of dispute within social epidemiology and medical sociology. Wilkinson and Pickett's The Spirit Level (2009), undoubtedly galvanised thinking across the disciplines, with its emphasis on how income inequality shapes the distribution of health and social problems. In this paper, we argue that their focus on income inequality, whilst important, understates the role of neoliberal discourses and practises in making sense of contemporary inequality and its health-related consequences. Many quantitative studies have demonstrated that more neoliberal countries have poorer health compared to less neoliberal countries, but there are few qualitative studies which explore how neoliberal discourses shape accounts and experiences and what protections and resources might be available to people. This article uses findings from a qualitative psycho-social study employing biographical-narrative interviews with women in Salford (England) to understand experiences of inequality as posited in The Spirit Level. We found evidence for the sorts of damages resulting from inequality as proposed in The Spirit Level. However, in addition to these, the most striking finding was the repeated articulation of a discourse which we have termed "no legitimate dependency". This was something both painful and damaging, where dependency of almost any sort was disavowed and responsibility was assumed by the self or "othered" in various ways. No legitimate dependency, we propose, is a partial (and problematic) internalisation of neoliberal discourses which becomes naturalised and unquestioned at the individual level. We speculate that these sorts of discourses in conjunction with a destruction of protective resources (both material and discursive), lead to an increase in strain and account in part for well-known damages consequent on life in an unequal society. We conclude that integrating understandings of neoliberalism into theorising about inequality enriches sociological perspectives in this area. PMID- 25137635 TI - The association between psychosocial stress and mortality is mediated by lifestyle and chronic diseases: the Hoorn Study. AB - Psychosocial stress is associated with chronic disease. We evaluated whether in the general population the number of stressful life events is associated with risk of mortality and whether this association is mediated by behavioral factors and morbidities. We conducted this study in the Hoorn cohort; a population-based cohort study among older men and women. Our main variable of interest was the number of stressful life events experienced during the previous 5 years, which were assessed by questionnaire. We calculated Cox proportional hazard ratios (HRs) for all-cause and cause-specific mortality during follow-up for those who experienced stressful life events compared to those who did not. We included 2385 participants (46% male; 62 +/- 7 years). During 20 years of follow-up 834 (35%) participants died, of whom 239 (28.6%) died of cardiovascular disease. Compared to the group with no stressful life events, the age, sex and socioeconomic status adjusted HRs (with 95% confidence intervals) for all-cause mortality, for the groups who had 1 event, 2 events, 3 events and >=4 events were 0.89 (0.72-1.09), 1.01 (0.81-1.24), 1.29 (1.00-1.66) and 1.44 (1.08-1.92), respectively. Similar results were observed for cardiovascular mortality. Mediation analysis showed that smoking, prevalent type 2 diabetes and cardiovascular disease were statistically significant mediators of the association between the number of stressful life events and mortality. Having 3 or more stressful life events is associated with a significantly increased risk for mortality in an elderly population-based cohort. This association is mediated by smoking, type 2 diabetes and cardiovascular disease. PMID- 25137637 TI - Histamine H1 receptor cell membrane chromatography online high-performance liquid chromatography with mass spectrometry method reveals houttuyfonate as an activator of the histamine H1 receptor. AB - Allergy is an abnormal reaction of the body to an allergen. Histamine is responsible for many of the acute symptoms of allergic diseases. Many of the allergic and inflammatory actions of histamine are mediated by the histamine H1 receptor. In the present study, we established a two-dimensional histamine H1 receptor/cell membrane chromatography with online high-performance liquid chromatography and mass spectrometry method for screening potential histamine activating components in a traditional Chinese medicine injection. The specification of the method was validated by screening, separating, and identifying a mixed standard solution of diphenhydramine hydrochloride, gefitinib, tamsulosin, and nitrendipine. The Yujin injection, an example of traditional Chinese medicine injection, was screened and potential allergic components acting on the histamine H1 receptor were identified. A Ca(2+) flux assay showed that houttuyfonate and Yujin injection induced calcium release in a dose-dependent manner. This suggests that houttuyfonate is an activator of the histamine H1 receptor. The mechanism of houttuyfonate activation involves phosphorylation of the inositol-1,4,5-trisphosphate receptor. In conclusion, this two-dimensional method can rapidly detect and enrich target components isolated from the Yujin injection. This indicates that individuals with an overexpression of the histamine H1 receptor should be aware of possible allergic reactions when receiving the Yujin injection. PMID- 25137639 TI - Role of Pb(II) defects in the mechanism of dissolution of plattnerite (beta-PbO2) in water under depleting chlorine conditions. AB - Destabilization of lead corrosion scales present in plumbing materials used in water distribution systems results in elevated lead concentrations in drinking water. Soluble lead release caused by changes in water chemistry has been linked to dissolution of lead carbonate and/or lead oxide solid phases. Although prior studies have examined the effects of varying water chemistry on the dissolution of plattnerite (beta-PbO2), beta-PbO2 dissolution under depleting chlorine conditions is poorly understood. This paper reports results obtained for long term batch dissolution experiments for solid phase beta-PbO2 under depleting chlorine conditions. Results indicate that the initial availability of free chlorine effectively depresses dissolved lead concentrations released from beta PbO2. However, the dissolved lead levels remained low (~4 MUg/L) even after free chlorine was depleted. Detailed spectroscopic characterization of solid samples collected during the beta-PbO2 experiments indicates that changes in the electronic structure of PbO2 occurred during the dissolution. This further points out that Pb2+ defects present in crystalline beta-PbO2 play a dominant role in the dissolution of this solid phase. PMID- 25137638 TI - Dual effects of familial Alzheimer's disease mutations (D7H, D7N, and H6R) on amyloid beta peptide: correlation dynamics and zinc binding. AB - Although the N-terminal region of Amyloid beta (Abeta) peptides plays dual roles as metal-coordinating sites and conformational modulator, few studies have been performed to explore the effects of mutations at this region on the overall conformational ensemble of Abeta and the binding propensity of metal ions. In this work, we focus on how three familial Alzheimer's disease mutations (D7H, D7N, and H6R) alter the structural characteristics and thermodynamic stabilities of Abeta42 using molecular dynamics simulations. We observe that each mutation displays increased beta-sheet structures in both N and C termini. In particular, both the N terminus and central hydrophobic region of D7H can form stable beta hairpin structures with its C terminus. The conserved turn structure at Val24 Lys28 in all peptides and Zn2+-bound Abeta42 is confirmed as the common structural motif to nucleate folding of Abeta. Each mutant can significantly increase the solvation free energy and thus enhance the aggregation of Abeta monomers. The correlation dynamics between Abeta(1-16) and Abeta(17-42) fragments are elucidated by linking the domain motions with the corresponding structured conformations. We characterize the different populations of correlated domain motions for each mutant from a more macroscopic perspective, and unexpectedly find that Zn2+-bound Abeta42 ensemble shares the same populations as Abeta42, indicating that the binding of Zn2+ to Abeta follows the conformational selection mechanism, and thus is independent of domain motions, even though the structures of Abeta have been modified at a residue level. PMID- 25137640 TI - Impaired development of neural-crest cell-derived organs and intellectual disability caused by MED13L haploinsufficiency. AB - MED13L is a component subunit of the Mediator complex, an important regulator of transcription that is highly conserved across eukaryotes. Here, we report MED13L disruption in a translocation t(12;19) breakpoint of a patient with Pierre-Robin syndrome, moderate intellectual disability, craniofacial anomalies, and muscular defects. The phenotype is similar to previously described patients with MED13L haploinsufficiency. Knockdown of MED13L orthologue in zebrafish, med13b, showed early defective migration of cranial neural crest cells (NCCs) that contributed to cartilage structure deformities in the later stage, recapitulating craniofacial anomalies seen in human patients. Notably, we observed abnormal distribution of developing neurons in different brain regions of med13b morphant embryos, which could be rescued upon introduction of full-length human MED13L mRNA. To compare with mammalian system, we suppressed MED13L expression by short hairpin RNA in ES-derived human neural progenitors, and differentiated them into neurons. Transcriptome analysis revealed differential expression of components of Wnt and FGF signaling pathways in MED13L-deficient neurons. Our finding provides a novel insight into the mechanism of overlapping phenotypic outcome targeting NCCs derivatives organs in patients with MED13L haploinsufficiency, and emphasizes a clinically recognizable syndromic phenotype in these patients. PMID- 25137641 TI - Hippocampal network oscillations - recent insights from in vitro experiments. AB - Network oscillations are present throughout the mammalian brain. They are important for certain cognitive functions, such as learning and memory. The hippocampus exhibits prominent oscillations similar to those seen in other parts of the cortex. Due to its highly organised lamellar structure, ex vivo and in vitro preparations from the hippocampus have provided experimental models within which to study network oscillations. As such, experiments in hippocampal slices continue to progress our understanding about both the mechanisms and functions of cortical network oscillations. Here, advances from the past two years are summarised, and the current state of the field discussed. PMID- 25137642 TI - Novel electrochemical fingerprinting methods for the precise determination of Pt(shell) coverage on Ru(core) nanoparticles. AB - The surface composition of nanoparticles is critical in defining their chemical and electrochemical properties. However, there are a limited number of tools that can rapidly and reliably establish these important characteristics at this small scale. In the present work, a series of Rucore@Ptshell nanoparticles (2 or 3 nm diameter Ru core, 0 to 2 monolayers of Pt in the shell layer) were synthesized and several novel electrochemical fingerprinting methods were developed to determine the Pt shell characteristics. These involved tracking the charge associated with the reduction of the oxide film formed on the exposed Rucore, as well as the potential and charge associated with COads stripping, giving the precise coverage of the first and second Pt monolayer, respectively. PMID- 25137643 TI - Trypanocidal activity of free and nanoencapsulated curcumin on Trypanosoma evansi. AB - This study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg(-1), intraperitoneally [i.p.]) and C-LNCs (10 mg kg(-1), i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0.05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi infected adult male Wistar rats. PMID- 25137644 TI - Healthcare system and the wealth-health gradient: a comparative study of older populations in six countries. AB - The present study provides a comparative analysis of the association between wealth and health in six healthcare systems (Sweden, the United Kingdom, Germany, the Czech Republic, Israel, the United States). National samples of individuals fifty years and over reveal considerable cross-country variations in health outcomes. In all six countries wealth and health are positively associated. The findings also show that state-based healthcare systems produce better population health outcomes than private-based healthcare systems. The results indicate that in five out of the six countries studied, the wealth-health gradients were remarkably similar, despite significant variations in healthcare system type. Only in the United States was the association between wealth and health substantially different from, and much greater than that in the other five countries. The findings suggest that private-based healthcare system in the U.S. is likely to promote stronger positive associations between wealth and health. PMID- 25137645 TI - Perceived quality of an alternative to acute hospitalization: an analytical study at a community hospital in Hallingdal, Norway. AB - There is growing international interest in the geography of health care provision, with health care providers searching for alternatives to acute hospitalization. In Norway, the government has recently legislated for municipal authorities to develop local health services for a selected group of patients, with a quality equal to or better than that provided by hospitals for emergency admissions. General practitioners in Hallingdal, a rural district in southern Norway, have for several years referred acutely somatically ill patients to a community hospital, Hallingdal sjukestugu (HSS). This article analyzes patients' perceived quality of HSS to demonstrate factors applicable nationally and internationally to aid in the development of local alternatives to general hospitals. We used a mixed-methods approach with questionnaires, individual interviews and a focus group interview. Sixty patients who were taking part in a randomized, controlled study of acute admissions at HSS answered the questionnaire. Selected patients were interviewed about their experiences and a focus group interview was conducted with representatives of local authorities, administrative personnel and health professionals. Patients admitted to HSS reported statistically significant greater satisfaction with several care aspects than those admitted to the general hospital. Factors highlighted by the patients were the quiet and homelike atmosphere; a small facility which allowed them a good overall view of the unit; close ties to the local community and continuity in the patient-staff relationship. The focus group members identified some overarching factors: an interdisciplinary and holistic approach, local ownership, proximity to local general practices and close cooperation with the specialist health services at the hospital. Most of these factors can be viewed as general elements relevant to the development of local alternatives to acute hospitalization both nationally and internationally. This study indicates that perceived quality should be one of the main motivations for developing alternatives to general hospital admissions. PMID- 25137646 TI - Enrolment of older people in social health protection programs in West Africa- does social exclusion play a part? AB - Although the population of older people in Africa is increasing, and older people are becoming increasingly vulnerable due to urbanisation, breakdown of family structures and rising healthcare costs, most African countries have no social health protection for older people. Two exceptions include Senegal's Plan Sesame, a user fees exemption for older people and Ghana's National Health Insurance Scheme (NHIS) where older people are exempt from paying premiums. Evidence on whether older people are aware of and enrolling in these schemes is however lacking. We aim to fill this gap. Besides exploring economic indicators, we also investigate whether social exclusion determines enrolment of older people. This is the first study that tries to explore the social, political, economic and cultural (SPEC) dimensions of social exclusion in the context of social health protection programs for older people. Data were collected by two cross-sectional household surveys conducted in Ghana and Senegal in 2012. We develop SPEC indices and conduct logistic regressions to study the determinants of enrolment. Our results indicate that older people vulnerable to social exclusion in all SPEC dimensions are less likely to enrol in Plan Sesame and those that are vulnerable in the political dimension are less likely to enrol in NHIS. Efforts should be taken to specifically enrol older people in rural areas, ethnic minorities, women and those isolated due to a lack of social support. Consideration should also be paid to modify scheme features such as eliminating the registration fee for older people in NHIS and creating administration offices for ID cards in remote communities in Senegal. PMID- 25137647 TI - Discovery of high affinity ligands for beta2-adrenergic receptor through pharmacophore-based high-throughput virtual screening and docking. AB - Novel high affinity compounds for human beta2-adrenergic receptor (beta2-AR) were searched among the clean drug-like subset of ZINC database consisting of 9,928,465 molecules that satisfy the Lipinski's rule of five. The screening protocol consisted of a high-throughput pharmacophore screening followed by an extensive amount of docking and rescoring. The pharmacophore model was composed of key features shared by all five inactive states of beta2-AR in complex with inverse agonists and antagonists. To test the discriminatory power of the pharmacophore model, a small-scale screening was initially performed on a database consisting of 117 compounds of which 53 antagonists were taken as active inhibitors and 64 agonists as inactive inhibitors. Accordingly, 7.3% of the ZINC database subset (729,413 compounds) satisfied the pharmacophore requirements, along with 44 antagonists and 17 agonists. Afterwards, all these hit compounds were docked to the inactive apo form of the receptor using various docking and scoring protocols. Following each docking experiment, the best pose was further evaluated based on the existence of key residues for antagonist binding in its vicinity. After final evaluations based on the human intestinal absorption (HIA) and the blood brain barrier (BBB) penetration properties, 62 hit compounds have been clustered based on their structural similarity and as a result four scaffolds were revealed. Two of these scaffolds were also observed in three high affinity compounds with experimentally known Ki values. Moreover, novel chemical compounds with distinct structures have been determined as potential beta2-AR drug candidates. PMID- 25137648 TI - Psychological distress and risk of peripheral vascular disease, abdominal aortic aneurysm, and heart failure: pooling of sixteen cohort studies. AB - OBJECTIVES: Examine the little-tested relation of psychological distress with peripheral vascular disease, abdominal aortic aneurysm, and heart failure. METHODS: Pooling of raw data from 166,631 male and female participants in 16 UK based cohort studies. Psychological distress was measured using the 12-item General Health Questionnaire. Peripheral vascular disease, abdominal aortic aneurysm, and heart failure events were based on death register linkage. RESULTS: During a mean follow-up 9.5 years there were 17,368 deaths of which 8625 were cardiovascular disease-related. Relative to the asymptomatic group (0 score), the highly distressed group (score 7-12) experienced an elevated risk of peripheral vascular disease (adjusted hazard ratio; 95% confidence interval: 3.39; 1.97, 5.82) and heart failure (1.76; 1.37, 2.26). Psychological distress was weakly related to the risk of death from abdominal aortic aneurysm. As anticipated, distress was associated with cardiovascular disease, coronary heart disease, and all strokes combined. CONCLUSIONS: In the present study, we provide new evidence of mental health-related cardiovascular disease presentations. PMID- 25137651 TI - Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in meconium for detection of alcohol abuse during pregnancy: Correlation study between both biomarkers. AB - This article presents results from 47 meconium samples, which were analyzed for fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) for detection of gestational alcohol consumption. A validated microwave assisted extraction (MAE) method in combination with GC-MS developed in the Institute of Forensic Science (Santiago de Compostela) was used for FAEE and the cumulative concentration of ethyl myristate, ethyl palmitate and ethyl stearate with a cut-off of 600ng/g was applied for interpretation. A simple method for identification and quantification of EtG has been evaluated by ultrasonication followed solid phase extraction (SPE). Successful validation parameters were obtained for both biochemical markers of alcohol intake. FAEE and EtG concentrations in meconium ranged between values lower than LOD and 32,892ng/g or 218ng/g respectively. We have analyzed FAEE and EtG in the same meconium aliquot, enabling comparison of the efficiency of gestational ethanol exposure detection. Certain agreement between the two biomarkers was found as they are both a very specific alcohol markers, making it a useful analysis for confirmation. PMID- 25137652 TI - An activity-integrated strategy involving ultra-high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry and fraction collector for rapid screening and characterization of the alpha-glucosidase inhibitors in Coptis chinensis Franch. (Huanglian). AB - An activity integrated strategy was established and validated to screen alpha glucosidase inhibitors by ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry and fraction collector (UHPLC/Q-TOF-MS-FC). UHPLC was used to separate the components in Coptis chinensis Franch. (Huanglian in Chinese) extract, which was identified by UHPLC-Q-TOF-MS to acquire structural information and collected by the fraction collector. Finally, the collected fractions were tested for inhibitory activity of alpha-glucosidase. The results showed that Huanglian extract had the alpha-glucosidase inhibitory activity with the IC50 value at 3.528mg mL(-1), which could be used for the treatment of diabetes. Alkaloids were the main components that had inhibitory activity of alpha-glucosidase in Huanglian extract, while the inhibitory activity of phenolic acids against alpha-glucosidase was relatively weaker. Coptisine, epiberberine, jatrorrhizin and berberine were screened and identified as alpha-glucosidase inhibitors from Huanglian extract in vitro. Compared with conventional methods, the integrated UHPLC/Q-TOF-MS-FC method could quantitatively analyze alpha glucosidase inhibitory activity of individual constituent and provide the total alpha-glucosidase inhibitory activity of the samples. The results demonstrated that the activity integrated UHPLC/Q-TOF-MS-FC method was an effective and powerful tool for screening and identifying active ingredients from Traditional Chinese medicines. PMID- 25137653 TI - Development of an improved ligand exchange chiral stationary phase based on leucinol for the resolution of proton pump inhibitors. AB - As an effort to develop improved ligand exchange chiral stationary phases (CSPs) for the resolution of chiral drugs, the residual silanol groups on the silica surface of a CSP based on sodium N-[(S)-1-hydroxymethyl-3-methylbutyl]-N undecylaminoacetate, a (S)-leucinol derivative, were protected with n-octyl groups. The residual silanol group-protected CSP was applied to the resolution of proton pump inhibitors (PPIs) such as omeprazole, pantoprazole, lansoprazole and rabeprazole. The resolution of PPIs on the residual silanol group-protected CSP was excellent with the separation factors (alpha) in the range of 4.32-6.42 and the resolution factors (RS) in the range of 6.70-7.15. The improved chiral recognition ability of the residual silanol group-protected CSP was rationalized to be originated from the protection of the non-enantioselective interaction sites on the silica surface and the improved lipophilicity of the stationary phase. PMID- 25137654 TI - Does nature have joints worth carving? A discussion of taxometrics, model-based clustering and latent variable mixture modeling. AB - Taxometric procedures, model-based clustering and latent variable mixture modeling (LVMM) are statistical methods that use the inter-relationships of observed symptoms or questionnaire items to investigate empirically whether the underlying psychiatric or psychological construct is dimensional or categorical. In this review we show why the results of such an investigation depend on the characteristics of the observed symptoms (e.g. symptom prevalence in the sample) and of the sample (e.g. clinical, population sample). Furthermore, the three methods differ with respect to their assumptions and therefore require different types of a priori knowledge about the observed symptoms and their inter relationships. We argue that the choice of method should optimally match and make use of the existing knowledge about the data that are analyzed. PMID- 25137658 TI - Contribution of contrast-enhanced ultrasound with Sonovue to describe the microvascularization of uterine fibroid tumors before and after uterine artery embolization. AB - OBJECTIVE: The principal objective of this study was to use contrast-enhanced ultrasonography to describe the characteristics of fibroid microvascularization before and after embolization. STUDY DESIGN: Forty women had contrast-enhanced ultrasonography with Sonovue((r)) injections before uterine artery embolization, the day afterwards, and at 6-12 months afterwards. An MRI was also performed before and after the procedure. RESULTS: Two thirds of the fibroids took up the contrast product before the myometrium did, and 45.8% were vascularized along the peripheral rim of the fibroid, compared with 41.6% with a principal pedicle and from the center in three (12.6%). After embolization at day one (D1), the myometrium was fully enhanced, that is, perfusion of the myometrium was plainly visible, in 25 cases (69.4%; n=36), partially enhanced in eight (22.2%), and totally avascular in three (8.4%). Analysis of the failures according to imaging criteria the day after embolization (D1) showed failure in seven women, with partial enhancement for six, and total for one. In the imaging at 6 months (M6), contrast ultrasonography showed failure for three women, with enhancement of the largest fibroid. This enhancement was total in two cases and partial (40%) in one. There were five failures according to MRI at M6, with partial enhancement. Only two of these failures were simultaneously failures according to the contrast enhanced ultrasonography. There were five clinical failures, two consistent with the imaging at 6 months and four predictable on D1. CONCLUSION: Contrast-enhanced ultrasonography is feasible and useful to understand fibroid vascularization and for monitoring embolization; its correlation with MRI is good, its concordance less so. PMID- 25137659 TI - Simply avoiding reactivating fear memory after exposure therapy may help to consolidate fear extinction memory--a reply. PMID- 25137673 TI - Synergetic gating of metal-latching ligands and metal-chelating proteins for mesoporous silica nanovehicles to enhance delivery efficiency. AB - Stimuli-responsive drug delivery systems are highly desirable for improved therapeutic efficacy and minimized adverse effects of drugs. Mesoporous silica nanoparticles (MSNs) functionalized with pentadentate ligands, N-(3 trimethoxysilylpropyl)ethylenediamine triacetate (TSP-DATA), in the presence of metal ions with and without myoglobin (Mb)-containing surface-accessible histidine residues, were constructed for pH-triggered controlled release. The DATA ligands immobilized on the MSN pore outlets could encapsulate cargo within the pores by metal latching across pore openings, and release efficiency increased with the increase of surface density of the DATA ligands. The release efficiencies for the metal-chelating protein nanogates, through multiple-site binding of Mb with the metal-chelating ligands, were higher than those for the metal-latching ligand nanogates but were almost independent of surface density of the ligands investigated. Both the metal-latching ligands and the metal-chelating proteins played a synergetic role in gating MSNs for high-loading drug delivery and stimuli-responsive controlled release. The constructed Mb-Cu(2+)-gated MSN delivery system has promising applications in targeted drug therapy of tumors. PMID- 25137681 TI - Uncertainty representation of grey numbers and grey sets. AB - In the literature, there is a presumption that a grey set and an interval-valued fuzzy set are equivalent. This presumption ignores the existence of discrete components in a grey number. In this paper, new measurements of uncertainties of grey numbers and grey sets, consisting of both absolute and relative uncertainties, are defined to give a comprehensive representation of uncertainties in a grey number and a grey set. Some simple examples are provided to illustrate that the proposed uncertainty measurement can give an effective representation of both absolute and relative uncertainties in a grey number and a grey set. The relationships between grey sets and interval-valued fuzzy sets are also analyzed from the point of view of the proposed uncertainty representation. The analysis demonstrates that grey sets and interval-valued fuzzy sets provide different but overlapping models for uncertainty representation in sets. PMID- 25137674 TI - Fluorinated polyimide gate dielectrics for the advancing the electrical stability of organic field-effect transistors. AB - Organic field-effect transistors (OFETs) that operated with good electrical stability were prepared by synthesizing fluorinated polyimide (PI) gate dielectrics based on 6FDA-PDA-PDA PI and 6FDA-CF3Bz-PDA PI. 6FDA-PDA-PDA PI and 6FDA-CF3Bz-PDA PI contain 6 and 18 fluorine atoms per repeat unit, respectively. These fluorinated polymers provided smooth surface topographies and surface energies that decreased as the number of fluorine atoms in the polymer backbone increased. These properties led to a better crystalline morphology in the semiconductor film grown over their surfaces. The number of fluorine atoms in the PI backbone increased, the field-effect mobility improved, and the threshold voltage shifted toward positive values (from -0.38 to +2.21 V) in the OFETs with pentacene and triethylsilylethynyl anthradithiophene. In addition, the highly fluorinated polyimide dielectric showed negligible hysteresis and a notable gate bias stability under both a N2 environment and ambient air. PMID- 25137682 TI - Distributed finite-time containment control for double-integrator multiagent systems. AB - In this paper, the distributed finite-time containment control problem for double integrator multiagent systems with multiple leaders and external disturbances is discussed. In the presence of multiple dynamic leaders, by utilizing the homogeneous control technique, a distributed finite-time observer is developed for the followers to estimate the weighted average of the leaders' velocities at first. Then, based on the estimates and the generalized adding a power integrator approach, distributed finite-time containment control algorithms are designed to guarantee that the states of the followers converge to the dynamic convex hull spanned by those of the leaders in finite time. Moreover, as a special case of multiple dynamic leaders with zero velocities, the proposed containment control algorithms also work for the case of multiple stationary leaders without using the distributed observer. Simulations demonstrate the effectiveness of the proposed control algorithms. PMID- 25137683 TI - Community-aware task allocation for social networked multiagent systems. AB - In this paper, we propose a novel community-aware task allocation model for social networked multiagent systems (SN-MASs), where the agent' cooperation domain is constrained in community and each agent can negotiate only with its intracommunity member agents. Under such community-aware scenarios, we prove that it remains NP-hard to maximize system overall profit. To solve this problem effectively, we present a heuristic algorithm that is composed of three phases: 1) task selection: select the desirable task to be allocated preferentially; 2) allocation to community: allocate the selected task to communities based on a significant task-first heuristics; and 3) allocation to agent: negotiate resources for the selected task based on a nonoverlap agent-first and breadth first resource negotiation mechanism. Through the theoretical analyses and experiments, the advantages of our presented heuristic algorithm and community aware task allocation model are validated. 1) Our presented heuristic algorithm performs very closely to the benchmark exponential brute-force optimal algorithm and the network flow-based greedy algorithm in terms of system overall profit in small-scale applications. Moreover, in the large-scale applications, the presented heuristic algorithm achieves approximately the same overall system profit, but significantly reduces the computational load compared with the greedy algorithm. 2) Our presented community-aware task allocation model reduces the system communication cost compared with the previous global-aware task allocation model and improves the system overall profit greatly compared with the previous local neighbor-aware task allocation model. PMID- 25137684 TI - Hyperspectral image classification using functional data analysis. AB - The large number of spectral bands acquired by hyperspectral imaging sensors allows us to better distinguish many subtle objects and materials. Unlike other classical hyperspectral image classification methods in the multivariate analysis framework, in this paper, a novel method using functional data analysis (FDA) for accurate classification of hyperspectral images has been proposed. The central idea of FDA is to treat multivariate data as continuous functions. From this perspective, the spectral curve of each pixel in the hyperspectral images is naturally viewed as a function. This can be beneficial for making full use of the abundant spectral information. The relevance between adjacent pixel elements in the hyperspectral images can also be utilized reasonably. Functional principal component analysis is applied to solve the classification problem of these functions. Experimental results on three hyperspectral images show that the proposed method can achieve higher classification accuracies in comparison to some state-of-the-art hyperspectral image classification methods. PMID- 25137685 TI - A new design of robust Hinfinity sliding mode control for uncertain stochastic T S fuzzy time-delay systems. AB - In this paper, a novel dynamic sliding mode control scheme is proposed for a class of uncertain stochastic nonlinear time-delay systems represented by Takagi Sugeno fuzzy models. The key advantage of the proposed scheme is that two very restrictive assumptions in most existing sliding mode control approaches for stochastic fuzzy systems have been removed. It is shown that the closed-loop control system trajectories can be driven onto the sliding surface in finite time almost certainly. It is also shown that the stochastic stability of the resulting sliding motion can be guaranteed in terms of linear matrix inequalities; moreover, the sliding-mode controller can be obtained simultaneously. Simulation results illustrating the advantages and effectiveness of the proposed approaches are also provided. PMID- 25137686 TI - Bare bones particle swarm optimization with scale matrix adaptation. AB - Bare bones particle swarm optimization (BBPSO) is a swarm algorithm that has shown potential for solving single-objective unconstrained optimization problems over continuous search spaces. However, it suffers of the premature convergence problem that means it may get trapped into a local optimum when solving multimodal problems. In order to address this drawback and improve the performance of the BBPSO, we propose a variant of this algorithm, named by us as BBPSO with scale matrix adaptation (SMA), SMA-BBPSO for short reference. In the SMA-BBPSO, the position of a particle is selected from a multivariate t distribution with a rule for adaptation of its scale matrix. We use the multivariate t-distribution in its hierarchical form, as a scale mixtures of normal distributions. The t -distribution has heavier tails than those of the normal distribution, which increases the ability of the particles to escape from a local optimum. In addition, our approach includes the normal distribution as a particular case. As a consequence, the t -distribution can be applied during the optimization process by maintaining the proper balance between exploration and exploitation. We also propose a simple update rule to adapt the scale matrix associated with a particle. Our strategy consists of adapting the scale matrix of a particle such that the best position found by any particle in its neighborhood is sampled with maximum likelihood in the next iteration. A theoretical analysis was developed to explain how the SMA-BBPSO works, and an empirical study was carried out to evaluate the performance of the proposed algorithm. The experimental results show the suitability of the proposed approach in terms of effectiveness to find good solutions for all benchmark problems investigated. Nonparametric statistical tests indicate that SMA-BBPSO shows a statistically significant improvement compared with other swarm algorithms. PMID- 25137687 TI - Exposure fusion using boosting Laplacian pyramid. AB - This paper proposes a new exposure fusion approach for producing a high quality image result from multiple exposure images. Based on the local weight and global weight by considering the exposure quality measurement between different exposure images, and the just noticeable distortion-based saliency weight, a novel hybrid exposure weight measurement is developed. This new hybrid weight is guided not only by a single image's exposure level but also by the relative exposure level between different exposure images. The core of the approach is our novel boosting Laplacian pyramid, which is based on the structure of boosting the detail and base signal, respectively, and the boosting process is guided by the proposed exposure weight. Our approach can effectively blend the multiple exposure images for static scenes while preserving both color appearance and texture structure. Our experimental results demonstrate that the proposed approach successfully produces visually pleasing exposure fusion images with better color appearance and more texture details than the existing exposure fusion techniques and tone mapping operators. PMID- 25137688 TI - Acquisition of causal models for local distributions in Bayesian networks. AB - To specify a Bayesian network, a local distribution in the form of a conditional probability table, often of an effect conditioned on its n causes, needs to be acquired, one for each non-root node. Since the number of parameters to be assessed is generally exponential in n , improving the efficiency is an important concern in knowledge engineering. Non-impeding noisy-AND (NIN-AND) tree causal models reduce the number of parameters to being linear in n , while explicitly expressing both reinforcing and undermining interactions among causes. The key challenge in NIN-AND tree modeling is the acquisition of the NIN-AND tree structure. In this paper, we formulate a concise structure representation and an expressive causal interaction function of NIN-AND trees. Building on these representations, we propose two structural acquisition methods, which are applicable to both elicitation-based and machine learning-based acquisitions. Their accuracy is demonstrated through experimental evaluations. PMID- 25137689 TI - Sensor-driven area coverage for an autonomous fixed-wing unmanned aerial vehicle. AB - Area coverage with an onboard sensor is an important task for an unmanned aerial vehicle (UAV) with many applications. Autonomous fixed-wing UAVs are more appropriate for larger scale area surveying since they can cover ground more quickly. However, their non-holonomic dynamics and susceptibility to disturbances make sensor coverage a challenging task. Most previous approaches to area coverage planning are offline and assume that the UAV can follow the planned trajectory exactly. In this paper, this restriction is removed as the aircraft maintains a coverage map based on its actual pose trajectory and makes control decisions based on that map. The aircraft is able to plan paths in situ based on sensor data and an accurate model of the on-board camera used for coverage. An information theoretic approach is used that selects desired headings that maximize the expected information gain over the coverage map. In addition, the branch entropy concept previously developed for autonomous underwater vehicles is extended to UAVs and ensures that the vehicle is able to achieve its global coverage mission. The coverage map over the workspace uses the projective camera model and compares the expected area of the target on the ground and the actual area covered on the ground by each pixel in the image. The camera is mounted on a two-axis gimbal and can either be stabilized or optimized for maximal coverage. Hardware-in-the-loop simulation results and real hardware implementation on a fixed-wing UAV show the effectiveness of the approach. By including the already developed automatic takeoff and landing capabilities, we now have a fully automated and robust platform for performing aerial imagery surveys. PMID- 25137690 TI - DEC: dynamically evolving clustering and its application to structure identification of evolving fuzzy models. AB - Identification of models from input-output data essentially requires estimation of appropriate cluster centers. In this paper, a new online evolving clustering approach for streaming data is proposed. Unlike other approaches that consider either the data density or distance from existing cluster centers, this approach uses cluster weight and distance before generating new clusters. To capture the dynamics of the data stream, the cluster weight is defined in both data and time space in such a way that it decays exponentially with time. It also applies concepts from computational geometry to determine the neighborhood information while forming clusters. A distinction is made between core and noncore clusters to effectively identify the real outliers. The approach efficiently estimates cluster centers upon which evolving Takagi-Sugeno models are developed. The experimental results with developed models show that the proposed approach attains results at par or better than existing approaches and significantly reduces the computational overhead, which makes it suitable for real-time applications. PMID- 25137691 TI - A generic method for the evaluation of interval type-2 fuzzy linguistic summaries. AB - Linguistic summarization has turned out to be an important knowledge discovery technique by providing the most relevant natural language-based sentences in a human consistent manner. While many studies on linguistic summarization have handled ordinary fuzzy sets [type-1 fuzzy set (T1FS)] for modeling words, only few of them have dealt with interval type-2 fuzzy sets (IT2FS) even though IT2FS is better capable of handling uncertainties associated with words. Furthermore, the existent studies work with the scalar cardinality based degree of truth which might lead to inconsistency in the evaluation of interval type-2 fuzzy (IT2F) linguistic summaries. In this paper, to overcome this shortcoming, we propose a novel probabilistic degree of truth for evaluating IT2F linguistic summaries in the forms of type-I and type-II quantified sentences. We also extend the properties that should be fulfilled by any degree of truth on linguistic summarization with T1FS to IT2F environment. We not only prove that our probabilistic degree of truth satisfies the given properties, but also illustrate by examples that it provides more consistent results when compared to the existing degree of truth in the literature. Furthermore, we carry out an application on linguistic summarization of time series data of Europe Brent Spot Price, along with a comparison of the results achieved with our approach and that of the existing degree of truth in the literature. PMID- 25137692 TI - Generalized Laplacian eigenmaps for modeling and tracking human motions. AB - This paper presents generalized Laplacian eigenmaps, a novel dimensionality reduction approach designed to address stylistic variations in time series. It generates compact and coherent continuous spaces whose geometry is data-driven. This paper also introduces graph-based particle filter, a novel methodology conceived for efficient tracking in low dimensional space derived from a spectral dimensionality reduction method. Its strengths are a propagation scheme, which facilitates the prediction in time and style, and a noise model coherent with the manifold, which prevents divergence, and increases robustness. Experiments show that a combination of both techniques achieves state-of-the-art performance for human pose tracking in underconstrained scenarios. PMID- 25137693 TI - Maximal entropy random walk for region-based visual saliency. AB - Visual saliency is attracting more and more research attention since it is beneficial to many computer vision applications. In this paper, we propose a novel bottom-up saliency model for detecting salient objects in natural images. First, inspired by the recent advance in the realm of statistical thermodynamics, we adopt a novel mathematical model, namely, the maximal entropy random walk (MERW) to measure saliency. We analyze the rationality and superiority of MERW for modeling visual saliency. Then, based on the MERW model, we establish a generic framework for saliency detection. Different from the vast majority of existing saliency models, our method is built on a purely region-based strategy, which is able to yield high-resolution saliency maps with well preserved object shapes and uniformly highlighted salient regions. In the proposed framework, the input image is first over-segmented into superpixels, which are taken as the primary units for subsequent procedures, and regional features are extracted. Then, saliency is measured according to two principles, i.e., uniqueness and visual organization, both implemented in a unified approach, i.e., the MERW model based on graph representation. Intensive experimental results on publicly available datasets demonstrate that our method outperforms the state-of-the-art saliency models. PMID- 25137694 TI - Significant body point labeling and tracking. AB - In this paper, a method is presented to label and track anatomical landmarks (e.g., head, hand/arm, feet), which are referred to as significant body points (SBPs), using implicit body models. By considering the human body as an inverted pendulum model, ellipse fitting and contour moments are applied to classify it as being in Stand, Sit, or Lie posture. A convex hull of the silhouette contour is used to determine the locations of SBPs. The particle filter or a motion flow based method is used to predict SBPs in occlusion. Stick figures of various activities are generated by connecting the SBPs. The qualitative and quantitative evaluation show that the proposed method robustly labels and tracks SBPs in various activities of two different (low and high) resolution data sets. PMID- 25137695 TI - A framework for biodynamic feedthrough analysis--part II: validation and application. AB - Biodynamic feedthrough (BDFT) is a complex phenomenon, that has been studied for several decades. However, there is little consensus on how to approach the BDFT problem in terms of definitions, nomenclature, and mathematical descriptions. In this paper, the framework for BDFT analysis, as presented in Part I of this dual publication, is validated and applied. The goal of this framework is twofold. First of all, it provides some common ground between the seemingly large range of different approaches existing in BDFT literature. Secondly, the framework itself allows for gaining new insights into BDFT phenomena. Using recently obtained measurement data, parts of the framework that were not already addressed elsewhere, are validated. As an example of a practical application of the framework, it will be demonstrated how the effects of control device dynamics on BDFT can be understood and accurately predicted. Other ways of employing the framework are illustrated by interpreting the results of three selected studies from the literature using the BDFT framework. The presentation of the BDFT framework is divided into two parts. This paper, Part II, addresses the validation and application of the framework. Part I, which is also published in this journal issue, addresses the theoretical foundations of the framework. The work is presented in two separate papers to allow for a detailed discussion of both the framework's theoretical background and its validation. PMID- 25137718 TI - High-resolution mesoscopic fluorescence molecular tomography based on compressive sensing. AB - Mesoscopic fluorescence molecular tomography (MFMT) is new imaging modality aiming at 3-D imaging of molecular probes in a few millimeter thick biological samples with high-spatial resolution. In this paper, we develop a compressive sensing-based reconstruction method with l1-norm regularization for MFMT with the goal of improving spatial resolution and stability of the optical inverse problem. Three-dimensional numerical simulations of anatomically accurate microvasculature and real data obtained from phantom experiments are employed to evaluate the merits of the proposed method. Experimental results show that the proposed method can achieve 80 MUm spatial resolution for a biological sample of 3 mm thickness and more accurate quantifications of concentrations and locations for the fluorophore distribution than those of the conventional methods. PMID- 25137719 TI - Novel active comb-shaped dry electrode for EEG measurement in hairy site. AB - Electroencephalography (EEG) is an important biopotential, and has been widely applied in clinical applications. The conventional EEG electrode with conductive gels is usually used for measuring EEG. However, the use of conductive gel also encounters with the issue of drying and hardening. Recently, many dry EEG electrodes based on different conductive materials and techniques were proposed to solve the previous issue. However, measuring EEG in the hairy site is still a difficult challenge. In this study, a novel active comb-shaped dry electrode was proposed to measure EEG in hairy site. Different form other comb-shaped or spike shaped dry electrodes, it can provide more excellent performance of avoiding the signal attenuation, phase distortion, and the reduction of common mode rejection ratio. Even under walking motion, it can effectively acquire EEG in hairy site. Finally, the experiments for alpha rhythm and steady-state visually evoked potential were also tested to validate the proposed electrode. PMID- 25137720 TI - Motion artifacts in capacitive ECG measurements: reducing the combined effect of DC voltages and capacitance changes using an injection signal. AB - Capacitive electrodes are a promising alternative to the conventional adhesive electrodes for ECG measurements. They provide more comfort to the patient when integrated in everyday objects (e.g., beds or seats) for long-term monitoring. However, the application of capacitive sensors is limited by their high sensitivity to motion artifacts. For example, motion at the body-electrode interface causes variations of the coupling capacitance which, in the presence of a dc voltage across the coupling capacitor, create strong artifacts in the measurements. The origin, relevance, and reduction of this specific and important type of artifacts are studied here. An injection signal is exploited to track the variations of the coupling capacitance in real time. This information is then used by an identification scheme to estimate the artifacts and subtract them from the measurements. The method was evaluated in simulations, lab environments, and in a real-life recording on an adult's chest. For the type of artifact under study, a strong artifact reduction ranging from 40 dB for simulated data to 9 dB for a given real-life recording was achieved. The proposed method is automated, does not require any knowledge about the measurement system parameters, and provides an online estimate for the dc voltage across the coupling capacitor. PMID- 25137721 TI - Four-class classification of skin lesions with task decomposition strategy. AB - This paper proposes a new computer-aided method for the skin lesion classification applicable to both melanocytic skin lesions (MSLs) and nonmelanocytic skin lesions (NoMSLs). The computer-aided skin lesion classification has drawn attention as an aid for detection of skin cancers. Several researchers have developed methods to distinguish between melanoma and nevus, which are both categorized as MSL. However, most of these studies did not focus on NoMSLs such as basal cell carcinoma (BCC), the most common skin cancer and seborrheic keratosis (SK) despite their high incidence rates. It is preferable to deal with these NoMSLs as well as MSLs especially for the potential users who are not enough capable of diagnosing pigmented skin lesions on their own such as dermatologists in training and physicians with different expertise. We developed a new method to distinguish among melanomas, nevi, BCCs, and SKs. Our method calculates 828 candidate features grouped into three categories: color, subregion, and texture. We introduced two types of classification models: a layered model that uses a task decomposition strategy and flat models to serve as performance baselines. We tested our methods on 964 dermoscopy images: 105 melanomas, 692 nevi, 69 BCCs, and 98 SKs. The layered model outperformed the flat models, achieving detection rates of 90.48%, 82.51%, 82.61%, and 80.61% for melanomas, nevi, BCCs, and SKs, respectively. We also identified specific features effective for the classification task including irregularity of color distribution. The results show promise for enhancing the capability of the computer-aided skin lesion classification. PMID- 25137722 TI - Identifying Virtual 3D Geometric Shapes with a Vibrotactile Glove. AB - The emergence of off-screen interaction devices is bringing the field of virtual reality to a broad range of applications where virtual objects can be manipulated without the use of traditional peripherals. However, to facilitate object interaction, other stimuli such as haptic feedback are necessary to improve the user experience. To enable the identification of virtual 3D objects without visual feedback, a haptic display based on a vibrotactile glove and multiple points of contact gives users an enhanced sensation of touching a virtual object with their hands. Experimental results demonstrate the capacity of this technology in practical applications. PMID- 25137724 TI - A Tool-Free Calibration Method for Turntable-Based 3D Scanning Systems. AB - Turntable-based 3D scanners are popular but require calibration of the turntable axis. Existing methods for turntable calibration typically make use of specially designed tools, such as a chessboard or criterion sphere, which users must manually install and dismount. In this article, the authors propose an automatic method to calibrate the turntable axis without any calibration tools. Given a scan sequence of the input object, they first recover the initial rotation axis from an automatic registration step. Then they apply an iterative procedure to obtain the optimized turntable axis. This iterative procedure alternates between two steps: refining the initial pose of the input scans and approximating the rotation matrix. The performance of the proposed method was evaluated on a structured light-based scanning system. PMID- 25137723 TI - Visualization beyond the desktop--the next big thing. AB - Visualization is coming of age. With visual depictions being seamlessly integrated into documents, and data visualization techniques being used to understand increasingly large and complex datasets, the term "visualization"' is becoming used in everyday conversations. But we are on a cusp; visualization researchers need to develop and adapt to today's new devices and tomorrow's technology. Today, people interact with visual depictions through a mouse. Tomorrow, they'll be touching, swiping, grasping, feeling, hearing, smelling, and even tasting data. The next big thing is multisensory visualization that goes beyond the desktop. PMID- 25137725 TI - Automated segmentation of breast in 3-D MR images using a robust atlas. AB - This paper presents a robust atlas-based segmentation (ABS) algorithm for segmentation of the breast boundary in 3-D MR images. The proposed algorithm combines the well-known methodologies of ABS namely probabilistic atlas and atlas selection approaches into a single framework where two configurations are realized. The algorithm uses phase congruency maps to create an atlas which is robust to intensity variations. This allows an atlas derived from images acquired with one MR imaging sequence to be used to segment images acquired with a different MR imaging sequence and eliminates the need for intensity-based registration. Images acquired using a Dixon sequence were used to create an atlas which was used to segment both Dixon images (intra-sequence) and T1-weighted images (inter-sequence). In both cases, highly accurate results were achieved with the median Dice similarity coefficient values of 94% +/-4% and 87 +/-6.5%, respectively. PMID- 25137726 TI - Bias reduction for low-statistics PET: maximum likelihood reconstruction with a modified Poisson distribution. AB - Positron emission tomography data are typically reconstructed with maximum likelihood expectation maximization (MLEM). However, MLEM suffers from positive bias due to the non-negativity constraint. This is particularly problematic for tracer kinetic modeling. Two reconstruction methods with bias reduction properties that do not use strict Poisson optimization are presented and compared to each other, to filtered backprojection (FBP), and to MLEM. The first method is an extension of NEGML, where the Poisson distribution is replaced by a Gaussian distribution for low count data points. The transition point between the Gaussian and the Poisson regime is a parameter of the model. The second method is a simplification of ABML. ABML has a lower and upper bound for the reconstructed image whereas AML has the upper bound set to infinity. AML uses a negative lower bound to obtain bias reduction properties. Different choices of the lower bound are studied. The parameter of both algorithms determines the effectiveness of the bias reduction and should be chosen large enough to ensure bias-free images. This means that both algorithms become more similar to least squares algorithms, which turned out to be necessary to obtain bias-free reconstructions. This comes at the cost of increased variance. Nevertheless, NEGML and AML have lower variance than FBP. Furthermore, randoms handling has a large influence on the bias. Reconstruction with smoothed randoms results in lower bias compared to reconstruction with unsmoothed randoms or randoms precorrected data. However, NEGML and AML yield both bias-free images for large values of their parameter. PMID- 25137727 TI - Compressive sensing of sparse tensors. AB - Compressive sensing (CS) has triggered an enormous research activity since its first appearance. CS exploits the signal's sparsity or compressibility in a particular domain and integrates data compression and acquisition, thus allowing exact reconstruction through relatively few nonadaptive linear measurements. While conventional CS theory relies on data representation in the form of vectors, many data types in various applications, such as color imaging, video sequences, and multisensor networks, are intrinsically represented by higher order tensors. Application of CS to higher order data representation is typically performed by conversion of the data to very long vectors that must be measured using very large sampling matrices, thus imposing a huge computational and memory burden. In this paper, we propose generalized tensor compressive sensing (GTCS)-a unified framework for CS of higher order tensors, which preserves the intrinsic structure of tensor data with reduced computational complexity at reconstruction. GTCS offers an efficient means for representation of multidimensional data by providing simultaneous acquisition and compression from all tensor modes. In addition, we propound two reconstruction procedures, a serial method and a parallelizable method. We then compare the performance of the proposed method with Kronecker compressive sensing (KCS) and multiway compressive sensing (MWCS). We demonstrate experimentally that GTCS outperforms KCS and MWCS in terms of both reconstruction accuracy (within a range of compression ratios) and processing speed. The major disadvantage of our methods (and of MWCS as well) is that the compression ratios may be worse than that offered by KCS. PMID- 25137728 TI - Topology preserving thinning of cell complexes. AB - A topology preserving skeleton is a synthetic representation of an object that retains its topology and many of its significant morphological properties. The process of obtaining the skeleton, referred to as skeletonization or thinning, is a very active research area. It plays a central role in reducing the amount of information to be processed during image analysis and visualization, computer aided diagnosis, or by pattern recognition algorithms. This paper introduces a novel topology preserving thinning algorithm, which removes simple cells-a generalization of simple points-of a given cell complex. The test for simple cells is based on acyclicity tables automatically produced in advance with homology computations. Using acyclicity tables render the implementation of thinning algorithms straightforward. Moreover, the fact that tables are automatically filled for all possible configurations allows to rigorously prove the generality of the algorithm and to obtain fool-proof implementations. The novel approach enables, for the first time, according to our knowledge, to thin a general unstructured simplicial complex. Acyclicity tables for cubical and simplicial complexes and an open source implementation of the thinning algorithm are provided as an additional material to allow their immediate use in the vast number of applications arising in medical imaging and beyond. PMID- 25137729 TI - On continuous user authentication via typing behavior. AB - We hypothesize that an individual computer user has a unique and consistent habitual pattern of hand movements, independent of the text, while typing on a keyboard. As a result, this paper proposes a novel biometric modality named typing behavior (TB) for continuous user authentication. Given a webcam pointing toward a keyboard, we develop real-time computer vision algorithms to automatically extract hand movement patterns from the video stream. Unlike the typical continuous biometrics, such as keystroke dynamics (KD), TB provides a reliable authentication with a short delay, while avoiding explicit key-logging. We collect a video database where 63 unique subjects type static text and free text for multiple sessions. For one typing video, the hands are segmented in each frame and a unique descriptor is extracted based on the shape and position of hands, as well as their temporal dynamics in the video sequence. We propose a novel approach, named bag of multi-dimensional phrases, to match the cross feature and cross-temporal pattern between a gallery sequence and probe sequence. The experimental results demonstrate a superior performance of TB when compared with KD, which, together with our ultrareal-time demo system, warrant further investigation of this novel vision application and biometric modality. PMID- 25137730 TI - Time-Varying Ankle Mechanical Impedance During Human Locomotion. AB - In human locomotion, we continuously modulate joint mechanical impedance of the lower limb (hip, knee, and ankle) either voluntarily or reflexively to accommodate environmental changes and maintain stable interaction. Ankle mechanical impedance plays a pivotal role at the interface between the neuro mechanical system and the physical world. This paper reports, for the first time, a characterization of human ankle mechanical impedance in two degrees-of-freedom simultaneously as it varies with time during walking. Ensemble-based linear time varying system identification methods implemented with a wearable ankle robot, Anklebot, enabled reliable estimation of ankle mechanical impedance from the pre swing phase through the entire swing phase to the early-stance phase. This included heel-strike and toe-off, key events in the transition from the swing to stance phase or vice versa. Time-varying ankle mechanical impedance was accurately approximated by a second order model consisting of inertia, viscosity, and stiffness in both inversion-eversion and dorsiflexion-plantarflexion directions, as observed in our previous steady-state dynamic studies. We found that viscosity and stiffness of the ankle significantly decreased at the end of the stance phase before toe-off, remained relatively constant across the swing phase, and increased around heel-strike. Closer investigation around heel-strike revealed that viscosity and stiffness in both planes increased before heel-strike occurred. This finding is important evidence of "pretuning" by the central nervous system. In addition, viscosity and stiffness were greater in the sagittal plane than in the frontal plane across all subgait phases, except the early stance phase. Comparison with previous studies and implications for clinical study of neurologically impaired patients are provided. PMID- 25137731 TI - An Intelligent Robotic Hospital Bed for Safe Transportation of Critical Neurosurgery Patients Along Crowded Hospital Corridors. AB - We present a novel design of an intelligent robotic hospital bed, named Flexbed, with autonomous navigation ability. The robotic bed is developed for fast and safe transportation of critical neurosurgery patients without changing beds. Flexbed is more efficient and safe during the transportation process comparing to the conventional hospital beds. Flexbed is able to avoid en-route obstacles with an efficient easy-to-implement collision avoidance strategy when an obstacle is nearby and to move towards its destination at maximum speed when there is no threat of collision. We present extensive simulation results of navigation of Flexbed in the crowded hospital corridor environments with moving obstacles. Moreover, results of experiments with Flexbed in the real world scenarios are also presented and discussed. PMID- 25137732 TI - Feasibility of Energy-Autonomous Wireless Microsensors for Biomedical Applications: Powering and Communication. AB - In this review, biomedical-related wireless miniature devices such as implantable medical devices, neural prostheses, embedded neural systems, and body area network systems are investigated and categorized. The two main subsystems of such designs, the RF subsystem and the energy source subsystem, are studied in detail. Different application classes are considered separately, focusing on their specific data rate and size characteristics. Also, the energy consumption of state-of-the-art communication practices is compared to the energy that can be generated by current energy scavenging devices, highlighting gaps and opportunities. The RF subsystem is classified, and the suitable architecture for each category of applications is highlighted. Finally, a new figure of merit suitable for wireless biomedical applications is introduced to measure the performance of these devices and assist the designer in selecting the proper system for the required application. This figure of merit can effectively fill the gap of a much required method for comparing different techniques in simulation stage before a final design is chosen for implementation. PMID- 25137733 TI - Optoelectronic Systems Trained With Backpropagation Through Time. AB - Delay-coupled optoelectronic systems form promising candidates to act as powerful information processing devices. In this brief, we consider such a system that has been studied before in the context of reservoir computing (RC). Instead of viewing the system as a random dynamical system, we see it as a true machine learning model, which can be fully optimized. We use a recently introduced extension of backpropagation through time, an optimization algorithm originally designed for recurrent neural networks, and use it to let the network perform a difficult phoneme recognition task. We show that full optimization of all system parameters of delay-coupled optoelectronics systems yields a significant improvement over the previously applied RC approach. PMID- 25137734 TI - Phase Oscillatory Network and Visual Pattern Recognition. AB - We explore a properly interconnected set of Kuramoto type oscillators that results in a new associative-memory network configuration, which includes second- and third-order additional terms in the Fourier expansion of the network's coupling. Investigation of the response of the network to different external stimuli indicates an increase in the network capability for coding and information retrieval. Comparison of the network output with that of an equivalent experiment with subjects, for recognizing perturbed binary patterns, shows comparable results between the two approaches. We also discuss the enhanced storage capacity of the network. PMID- 25137736 TI - Universal fuzzy models and universal fuzzy controllers for discrete-time nonlinear systems. AB - This paper investigates the problems of universal fuzzy model and universal fuzzy controller for discrete-time nonaffine nonlinear systems (NNSs). It is shown that a kind of generalized T-S fuzzy model is the universal fuzzy model for discrete time NNSs satisfying a sufficient condition. The results on universal fuzzy controllers are presented for two classes of discrete-time stabilizable NNSs. Constructive procedures are provided to construct the model reference fuzzy controllers. The simulation example of an inverted pendulum is presented to illustrate the effectiveness and advantages of the proposed method. These results significantly extend the approach for potential applications in solving complex engineering problems. PMID- 25137737 TI - A new evolutionary algorithm with structure mutation for the maximum balanced biclique problem. AB - The maximum balanced biclique problem (MBBP), an NP-hard combinatorial optimization problem, has been attracting more attention in recent years. Existing node-deletion-based algorithms usually fail to find high-quality solutions due to their easy stagnation in local optima, especially when the scale of the problem grows large. In this paper, a new algorithm for the MBBP, evolutionary algorithm with structure mutation (EA/SM), is proposed. In the EA/SM framework, local search complemented with a repair-assisted restart process is adopted. A new mutation operator, SM, is proposed to enhance the exploration during the local search process. The SM can change the structure of solutions dynamically while keeping their size (fitness) and the feasibility unchanged. It implements a kind of large mutation in the structure space of MBBP to help the algorithm escape from local optima. An MBBP-specific local search operator is designed to improve the quality of solutions efficiently; besides, a new repair assisted restart process is introduced, in which the Marchiori's heuristic repair is modified to repair every new solution reinitialized by an estimation of distribution algorithm (EDA)-like process. The proposed algorithm is evaluated on a large set of benchmark graphs with various scales and densities. Experimental results show that: 1) EA/SM produces significantly better results than the state of-the-art heuristic algorithms; 2) it also outperforms a repair-based EDA and a repair-based genetic algorithm on all benchmark graphs; and 3) the advantages of EA/SM are mainly due to the introduction of the new SM operator and the new repair-assisted restart process. PMID- 25137738 TI - Active learning with imbalanced multiple noisy labeling. AB - With crowdsourcing systems, it is easy to collect multiple noisy labels for the same object for supervised learning. This dynamic annotation procedure fits the active learning perspective and accompanies the imbalanced multiple noisy labeling problem. This paper proposes a novel active learning framework with multiple imperfect annotators involved in crowdsourcing systems. The framework contains two core procedures: label integration and instance selection. In the label integration procedure, a positive label threshold (PLAT) algorithm is introduced to induce the class membership from the multiple noisy label set of each instance in a training set. PLAT solves the imbalanced labeling problem by dynamically adjusting the threshold for determining the class membership of an example. Furthermore, three novel instance selection strategies are proposed to adapt PLAT for improving the learning performance. These strategies are respectively based on the uncertainty derived from the multiple labels, the uncertainty derived from the learned model, and the combination method (CFI). Experimental results on 12 datasets with different underlying class distributions demonstrate that the three novel instance selection strategies significantly improve the learning performance, and CFI has the best performance when labeling behaviors exhibit different levels of imbalance in crowdsourcing systems. We also apply our methods to a real-world scenario, obtaining noisy labels from Amazon Mechanical Turk, and show that our proposed strategies achieve very high performance. PMID- 25137739 TI - A dual-population differential evolution with coevolution for constrained optimization. AB - Inspired by the fact that in modern society, team cooperation and the division of labor play important roles in accomplishing a task, this paper proposes a dual population differential evolution (DPDE) with coevolution for constrained optimization problems (COPs). The COP is treated as a bi-objective optimization problem where the first objective is the actual cost or reward function to be optimized, while the second objective accounts for the degree of constraint violations. At each generation during the evolution process, the whole population is divided into two based on the solution's feasibility to treat the both objectives separately. Each subpopulation focuses on only optimizing the corresponding objective which leads to a clear division of work. Furthermore, DPDE makes use of an information-sharing strategy to exchange search information between the different subpopulations similar to the team cooperation. The comparison of the proposed method on a number of benchmark functions with selected state-of-the-art constraint-handling algorithms indicates that the proposed technique performs competitively and effectively. PMID- 25137740 TI - New techniques for mining frequent patterns in unordered trees. AB - We consider a new tree mining problem that aims to discover restrictedly embedded subtree patterns from a set of rooted labeled unordered trees. We study the properties of a canonical form of unordered trees, and develop new Apriori-based techniques to generate all candidate subtrees level by level through two efficient rightmost expansion operations: 1) pairwise joining and 2) leg attachment. Next, we show that restrictedly embedded subtree detection can be achieved by calculating the restricted edit distance between a candidate subtree and a data tree. These techniques are then integrated into an efficient algorithm, named frequent restrictedly embedded subtree miner (FRESTM), to solve the tree mining problem at hand. The correctness of the FRESTM algorithm is proved and the time and space complexities of the algorithm are discussed. Experimental results on synthetic and real-world data demonstrate the effectiveness of the proposed approach. PMID- 25137752 TI - Case reports have a low priority in the EJPD. PMID- 25137753 TI - On whole person care. Dementia road map must transcend politics. PMID- 25137754 TI - The NHS must build resilience. PMID- 25137755 TI - Patient engagement. Press the right buttons to activate your patients. PMID- 25137756 TI - Patient records. The dataset with no name. PMID- 25137757 TI - Patient records: case studies. Return to the source. How health researchers are already using pseudonymisation of data at source. PMID- 25137758 TI - Service improvement. The exemplar hospital. PMID- 25137759 TI - Enhanced perspective. PMID- 25137760 TI - Frail older people improve their care. Pave the way for better elderly care. PMID- 25137761 TI - Lessons from a school master. PMID- 25137762 TI - Power up staff with hands-on action. PMID- 25137763 TI - [The world of Toulouse-Lautrec--litographies of the Museum of Fine Arts]. PMID- 25137764 TI - [Dilemmas of studying rare diseases]. PMID- 25137765 TI - [The cultural history of the discovery of insulin]. PMID- 25137766 TI - [Correlations of health, happiness and wellbeing in modern society]. PMID- 25137767 TI - [Neuroethics]. PMID- 25137768 TI - The dishonest math of PPACA. PMID- 25137769 TI - Severe ocular trauma in the emergency room. AB - To assess the nature, severity, and mechanisms of ocular trauma in the emergency room at an academic teaching hospital. METHODS: Individual review of patients' records involving ocular trauma in the emergency room. Severe intraocular trauma was defined as any injury that required intraocular surgery, any traumatic optic neuropathy, or total destruction of the eye. RESULTS: Of 519 patients in 2010 seen in the emergency room for ocular trauma, 52 patients (10%) had severe ocular trauma. Contusions (17) were the most common injury, followed closely by penetrating lacerations (16) and ruptures (16). In addition, 33 of these 52 patients (63.5%) had a full-thickness open globe injury, with physical assault as the most common etiology. CONCLUSION: The most common severe ocular traumas seen in the emergency room were contusions, penetrating lacerations, and ruptures. Penetrating lacerations and ruptures were the most common causes of open eye wall injuries. PMID- 25137770 TI - The Mississippi State Tuberculosis Sanatorium and the evolution of thoracic surgery in Mississippi. PMID- 25137771 TI - Call the surgeon please. PMID- 25137773 TI - No room for error. PMID- 25137772 TI - More thoughts on Medicaid expansion. PMID- 25137774 TI - The Veterans Administration Hospital scandal: views of a Mississippi physician. PMID- 25137775 TI - Securing the future of healthcare: students in your practice. PMID- 25137776 TI - Stepping up to leadership: why oral health? PMID- 25137777 TI - Thematic analysis of personal statements in physician assistant program admissions. AB - PURPOSE: The written personal statement is widely used in health professions program admissions. The purposes of this study were to identify the common themes manifesting in the personal statements of physician assistant (PA) program applicants and to measure the odds of matriculation while controlling for other admission covariates. METHODS: This study was a retrospective mixed-method observational study of CASPA admissions data. From the aggregate pool of 14,682 CASPA applications in the 2009-2010 admissions cycle, we randomly selected a subset of 600 unique de-identified applicants with complete application data. We coded the major themes and subthemes for each personal statement. We then performed maximum likelihood logistic regression analysis that compared the odds of matriculation based on the major themes and known cognitive admission variables. RESULTS: We identified eight major themes including altruism and the desire to help people, challenges and hardships, experience, key accomplishments, personal characteristics, positive perception of PA career attributes, role models, and a religious or spiritual quest. The only major theme increasing the odds of matriculation was role models, specifically exposure to a PA role model. Grade-point average far exceeded all other variables influencing the odds of matriculation. CONCLUSIONS: In this study, we found the personal statement to be an unreliable tool for predicting successful PA program matriculation. PMID- 25137778 TI - Generation 1.5--a different kind of millennial student. AB - Much attention has been paid to so-called "millennial students" in recent years, particularly regarding their relationship to technology, learning, and communication. Less notice has been taken of another kind of millennial student increasingly represented in our classrooms --those who were born in another country, but received a significant amount of their schooling here. Often referred to as Generation 1.5 because they have language characteristics in common with first- and second-generation immigrants, these bilingual students are a valuable resource for the physician assistant (PA) profession. However, just as teaching native-born millennial students may require some adjustment of instructional methods, Generation 1.5 students will require PA educators to pay closer attention to some aspects of teaching and learning. This article will discuss some of the particular challenges that Generation 1.5 students face and will argue that these challenges can be met in ways that are likely to help other nontraditional students as well. PMID- 25137779 TI - Physician assistant specialty choice: a factor analysis. AB - PURPOSE: The purpose of this study was to identify factors related to physician assistant (PA) graduates' specialty choice. METHODS: A web-based cross-sectional study of PAs graduating between 2007 and 2009 was conducted (N = 12,128). Factor analysis was performed on 897 useable survey responses. The cohort profile resembles that of recent AAPA census data regarding demographic and specialty choice distribution. RESULTS: Principal component factor analysis of perception items identified five factors that explained 52.6% of the response variance. Factors included personal satisfaction, intellectual challenge, patient care commitment, image of primary care, and professional satisfaction. The influence items analysis yielded five factors, explained 45.2% of the variance, and included practice environment, nature of patient care, lifestyle, employment opportunities, and risk aversion. These factors parallel previous findings of Hauer, et al. CONCLUSIONS: Identification of factors affecting specialty choice should provide an enhanced understanding to organizations as they explore strategies to increase recruitment and expansion of the primary care workforce. PMID- 25137780 TI - Utilization of a self-selection process for clinical rotation assignments: a report on student and clinical coordinator satisfaction. AB - PURPOSE: The purpose of this study was to examine the effect of a self-selection process for clinical rotation on student satisfaction with the program. Chatham University provides its students with the opportunity to self-select all of their clinical rotations from a list of pre-approved sites that have been determined to meet accreditation standards. METHODS: A survey was administered to all senior students enrolled in Chatham's Physician Assistant Program to assess their perceptions of the self-selection clerkship process. In addition, a survey was sent to all clinical coordinators nationwide to determine the techniques they used at their programs to assign students to rotation sites. RESULTS: Of the program's 61 students, 52 participated, yielding an 85.2% response rate. It was determined that students are very satisfied with the process of self-selection of the clinical rotation sites. Students reported that they take greater ownership in their rotations, because they were assigned to the rotations they wanted. Rotation self-selection was also reported as a desired feature of our program. Of 192 clinical coordinators that received the survey, 46 participated, and we found that 57% allow self-selection for elective rotations, and 43% do not allow selection of any rotations. CONCLUSIONS: Despite limitations such as loss of sites and preceptor turnover, the self-selection process is beneficial for both students and clinical coordinators. The process used could be easily adapted to other physician assistant programs. PMID- 25137782 TI - Culture, diversity, race, and the standards: assessing and addressing the hidden curricula. PMID- 25137781 TI - Nasal carriage of Staphylococcus aureus in physician assistant students: initial prevalence and transmission during clinical rotations. AB - PURPOSE: This study evaluated physician assistant (PA) students for nasal carriage of Staphylococcus aureus (prerotations) and then again just prior to graduation. It also attempted to correlate initial and subsequent sample results with subject-specific survey data relating to students' general medical, social, behavioral, and geographical situations. METHODS: Nasal swab cultures were self collected using standardized techniques. Colonies suspicious for Staph underwent further workup to determine if Staphylococcus aureus was present. RESULTS: Nine (eight females, one male) of 34 subjects (26.5%) were positive for Methicillin sensitive Staphylococcus aureus (MSSA) in the nares at baseline and all nine subjects remained positive during the second sampling. No subjects were found to have Methicillin-resistant Staphylococcus aureus (MRSA) at baseline and no subjects were positive for MRSA during phase two sampling. Routine sharing of drinks from common glassware was identified in all positive subjects, while subjects negative for colonization reported only seldom or no participation in that activity (P < 0.001). CONCLUSIONS: Clinical rotations did not appear to alter carriage status. However, a strong association between nasal carriage and participation in certain social behaviors was observed. PMID- 25137783 TI - Targeting instructional strategies to address Gen Y learner characteristics. PMID- 25137784 TI - Things we wish we'd known before physician assistant school: a physician assistant student survival guide. PMID- 25137785 TI - Fostering lifelong learning in the physician assistant student through internet based continuing medical education. PMID- 25137786 TI - National Nurses Week highlights the many leadership roles of nurses. PMID- 25137788 TI - A bundle strategy including patient hand hygiene to decrease clostridium difficile infections. AB - Prevention strategies for Clostridium difficile infection traditionally have addressed barrier precautions, environmental disinfection, and health care worker hand hygiene. When applied as a bundle, this approach has been used widely as an evidence-based strategy to prevent hospital-acquired C. difficile infection. Expanding the bundle to include patient hand hygiene is a nurse-driven approach to prevent C. difficile transmission. PMID- 25137787 TI - Seriously now...hospital food is no joke. PMID- 25137789 TI - Empowering the development of a nurse-driven protocol. AB - Results from a research project examining nurses' knowledge of diabetes empowered direct-care nurses to develop a hypoglycemia protocol, increasing accountability for the care provided and helping move from tradition-based to evidence-based practice. PMID- 25137790 TI - Stemming the obesity epidemic: are nurses credible coaches? AB - Obesity has become a health crisis in the United States, leading to serious physical, social, and psychological outcomes. Nurses are obese in the same proportion as the general population, which may discredit them as role models of and educators for healthful living. PMID- 25137791 TI - Decision-making models used by medical-surgical nurses to activate rapid response teams. AB - Medical-surgical nurses were queried about the decision-making process used to request assistance from the rapid response team (RRT). Results indicated the type of process is correlated to the frequency of RRT calls made. PMID- 25137792 TI - Taste dysfunction and eating behaviors in survivors of head and neck cancer treatment. AB - Radiation, chemotherapy, and surgery result in eating problems for patients with head and neck cancer. Eating is essential to physical and social functioning. Strategies for head and neck cancer survivors to cope with eating and taste impairments are reported in this study. PMID- 25137793 TI - Postoperative management of patients with obstructive sleep apnea: implications for the medical-surgical nurse. AB - Obstructive sleep apnea (OSA) affects up to 7% of Americans, and those undergoing surgery are at risk for complications. Medical-surgical nurses should be knowledgeable regarding this common disorder and understand how to screen effectively and monitor patients with OSA. PMID- 25137794 TI - Nursing knowledge of physiological and psychological outcomes related to patient sleep deprivation in the acute care setting. AB - In this study, nurses' knowledge regarding sleep quality outcomes in the acutely ill patient population was assessed. Also evaluated was the possible impact of nurses' knowledge of the effects of quality sleep on their choice of activities to promote patient rest. PMID- 25137796 TI - Use of theoretical frameworks in research. PMID- 25137795 TI - Making ABGs simple. PMID- 25137798 TI - Monkey in the middle! PMID- 25137797 TI - Informed consent: whose duty to inform? PMID- 25137799 TI - Harm reduction: compassionate care of persons with addictions. PMID- 25137800 TI - Conscientious objection in nursing: definition and criteria for acceptance. PMID- 25137802 TI - A compromise. PMID- 25137801 TI - Clement Victor Vignes, A.M., D.D.S.,D.SC., F.A.C.D. PMID- 25137803 TI - Governmental affairs and national initiative update. PMID- 25137804 TI - Do you remember? PMID- 25137805 TI - Computer placement in the treatment rooms. PMID- 25137806 TI - The Family Bank Trust. PMID- 25137807 TI - Clinical analytics for data-driven models of care. PMID- 25137808 TI - A population-based care transition model for chronically ill elders. AB - Elders with chronic illness are hospitalized more often than those without major chronic disease, and nearly one-fifth of hospitalizations result in re-admission within 30 days of discharge from the hospital. Care transition management programs address chronic disease complexity to reduce unnecessary hospitalization, improve quality of care, and reduce medical expense. This report describes how informatics influenced the transformation of a regional managed care organization from one focused on specific chronic disease prevalence to one targeting population-specific chronic conditions based on complexity. The key implication of these results is that population-based informatics can amplify the impact of programs designed to improve quality and prevent avoidable admissions and, at the same time, speed the rate of translation of evidence-based interventions to entire populations. This approach demonstrated an effective, efficient way to translate evidence-based research to the Medicare population, smoothing the transition back into the community, and preventing avoidable hospital admissions. PMID- 25137809 TI - Group visits for chronic illness management: implementation challenges and recommendations. AB - The group visit approach to improve chronic illness self-management appears promising in terms of selected outcomes, but little information is available about best ways to organize and implement group visits. This literature review of 84 articles identified group visit implementation challenges, including lack of a group visit billing code, inadequate administrative support and resources, difficult participant recruitment and retention, and logistical issues such as space and scheduling. Recommendations for future implementation initiatives were also abstracted from the literature. Patients and providers can benefit from well planned and well-conducted group visits. These benefits include greater patient and provider satisfaction, reduced overall utilization, improved clinical outcomes, and greater provider efficiency and productivity. PMID- 25137810 TI - A hospital system approach at decreasing falls with injuries and cost. AB - Falls and fall-related injuries continue to challenge every health care organization. Falls are a nurse-sensitive quality outcome. Patient falls are a leading cause of injuries in hospitals, considered to be among the most expensive adverse event, and continue to be a patient safety concern. Researchers analyzed the impact of a standardized fall prevention program across 50 acute care hospitals in 11 states. The implementation of a standardized multifactorial program for adult patients appears to have reduced falls with injuries by 58.3% over a 2-year period, allowing for a potential cost avoidance reduction of $776,064 in 2013 dollars. PMID- 25137811 TI - Nurse staffing and the relationship to job satisfaction and retention. AB - The purpose of this quantitative, correlational research study was to examine the relationships between nurse staffing, job satisfaction, and nurse retention in an acute care hospital environment. Results indicated a moderately strong, inverse relationship between job satisfaction and nurse retention. A weak positive relationship between job satisfaction and nurse staffing was identified. Nurses reported experiencing job dissatisfaction in the past 6 months specifically related to the number of patients assigned. Analysis suggested nurses are staying with their current employer because of the current economic environment. Improving nurse staffing will be necessary when the economy improves to prevent the departure of discontented nurses from acute care facilities. PMID- 25137812 TI - Hospital performance in China: do location and hospital level matter? AB - In this study, the operational and financial differences of hospitals were assessed by geographical area and by various levels of government ownership. Hospital geographic location (east, middle, and west) had a significant impact on hospital financial performance, but no significant influence on operational performance. Hospital government ownership level (province, city, and county) had a significant influence on both operational and financial performance. China's current public policy of not fully subsidizing its public hospital systems and limiting their ability to set prices for certain health care services may have negative and unintended consequences in its ability to provide needed health care services to its population. The government should revisit its policies to eliminate the differences regarding hospital performance related to location and government ownership levels. PMID- 25137813 TI - Building staffing science: two milestones. AB - Health care and nurse staffing present interesting challenges for nursing and health care leaders. The recently released Evidence and Excellence in Staffing (2nd edition) creates a framework for research and organizational improvement that leads to the development and sharing of best practices. A new model for staffing excellence has emerged with five core concepts. This new position paper calls for generating and disseminating 25-30 new best practices in nurse staffing across the care continuum over the next 3 years. PMID- 25137815 TI - Caring for myself so that I can care for others. PMID- 25137814 TI - Planes, trains, and other interruptions: such is life! AB - Nurse leaders can spend a significant part of their careers traveling. Self-care and personal mindfulness need not suffer when we are away from home and our normal routine. Personal health plans can be adapted in practical ways to travel with you. So pack your bags with whatever feeds your self-nurturing needs, grab some kale chips and comfortable shoes, and let's get going! PMID- 25137816 TI - Waiting for your coronation: a career-limiting trap. AB - Women are often reluctant to apply for promotions even when they are well deserved, simply believing good job performance will naturally lead to rewards. This phenomenon of advancement reticence has led to such labels as "tiara syndrome," "girl disease", and "imposter syndrome". Women often undervalue their skills and are less effective at self-promotion than their male counterparts. A number of strategies can help battle these "syndromes" and ease the stress of "taking off the tiara". PMID- 25137817 TI - Using the lens of history to understand nursing practice and policy: an interview with Julie Fairman. PMID- 25137818 TI - Paying it forward: Nursing Economic$ award winners reflect. PMID- 25137819 TI - I Love Lucy, George C. and Twitty too. PMID- 25137820 TI - Alan Kirk Wilson, MD. Focused physician has presidential ambitions for AMS member participation. PMID- 25137821 TI - 2014 hypertension and cholesterol guidelines. PMID- 25137822 TI - 2014 Awards Luncheon recognition for outstanding service. PMID- 25137823 TI - Highlights from House of Delegates meeting & word from the AMA. PMID- 25137824 TI - Physician communication in a social media climate. To share or not to share- thoughts on each side. PMID- 25137825 TI - Arkansas payment improvement initiative. Episodes of care update. PMID- 25137826 TI - Historical insights in the progression and development of gingivectomy. AB - During the last three centuries since the identification of periodontal disease, various non-surgical and surgical forms of periodontal therapy have been described and documented in the dental literature. The main objective of periodontal treatment has been initially the removal of "diseased gingiva," either through the implementation of various surgical techniques, or through the application of caustic drugs or pressing patches. Although the differences in the suggested techniques created significant controversies between some of the greatest clinicians and researchers in dentistry, their main goals remained the rehabilitation of the oral cavity and the therapeutic management of the problems sustained from periodontal disease. PMID- 25137827 TI - A short history of the Royal Odonto Chirurgical Society of Scotland. AB - In the mid-19th Century, the practice of dentistry in Britain was unregulated and chaotic. Organised training was non-existent, and the public was unable to be assured of satisfactory, ethical treatment. A group of Scottish practitioners, led by John Smith, an Edinburgh surgeon, established the Odonto Chirurgical Society of Scotland in 1867 as an ethical dental society promoting education and regulation of the emerging profession. The Society has prospered over the years. It was granted the title "Royal" on the occasion of its centenary in 1967, and approaches its 150th year with confidence. PMID- 25137828 TI - Historical perspectives on the roots of the apical negative pressure irrigation technique in endodontics. AB - The removal of the infectious process caused by an abscess in the periapical tissues was a challenge to dentists in the early part of the 20th century. While they recognized the need to debride the periapical tissues, the process was slow, tedious, and often fraught with failure that resulted in tooth extraction. However, with some creative ingenuity, an irrigation-suction apparatus was developed in the 1930s that enabled rapid and thorough debridement. This appliance went through multiple developmental permutations and was successful in achieving the desired goal. Interestingly, while the purpose of this device was a controlled periapical debridement through the root canal, and not necessarily a focus on a cleaning of the intricacies of the root canal system, the basic concept purported was similar to contemporary approaches used in root canal debridement today. PMID- 25137829 TI - Dental Postcards LV. Dr. Ernest A Carpenter: an early advocate of preventive dentistry. PMID- 25137830 TI - Dental trade cards XL. A toothbush in hand. PMID- 25137831 TI - What stress is doing to your brain. PMID- 25137833 TI - Diabetic cooking. PMID- 25137832 TI - Family awareness. Monitoring diabetes risk. PMID- 25137834 TI - Blood glucose self-monitoring. Part 2: monitoring technique. AB - To measure the concentration of glucose in your blood, you put a strip in the meter, poke a hole in your finger to get a sample of blood, touch the tip of the test strip to the drop of blood, and wait for the result. It sounds pretty straightforward. But, of course, the devil is in the details. PMID- 25137835 TI - Talking about diabetes. Six tips for improved communication. PMID- 25137837 TI - [An expert in integrative medical cardiology]. PMID- 25137836 TI - What your doctor is reading.ore evidence for value of bariatric surgery. PMID- 25137838 TI - [Several problems we should pay attention to in scientific research on integrative medicine]. PMID- 25137839 TI - [Therapeutic effect of Astragalus and Angelica mixture on the renal function and TCM syndrome factors in treating stage 3 and 4 chronic kidney disease patients]. AB - OBJECTIVE: To compare the therapeutic effect of Astragalus and Angelica Mixture (AAM) on treating CKD patients according to different CKD primary diseases, staging and TCM syndromes. METHODS: A multicentre, open-label, and self control clinical design was used, and thirty-two patients in line with inclusive criteria were recruited. Based on maintaining their previous basic CKD treatment, patients additionally took AAM (Astragalus and Angelica each 30 g), once a day, three months consisted of one therapeutic course. Serum creatinine (SCr), estimated glomerular filtration rate (eG- FR), 24 h urinary total protein (UTP), plasma albumin (ALB), hemoglobin (Hb), and changes of TCM syndrome factor integrals were compared before treatment, at the end of month 1, 2, and 3. The differences in the aforesaid indices were compared between CKD patients with different CKD primary diseases (chronic glomerulonephritis, chronic renal tubulointerstitial disease, hypertensive renal damage), different CKD stages (CKD 3 and CKD 4), and patients of qi-blood deficiency syndrome (QBDS) and non-QBDS. RESULTS: AAM could improve 78.12% (25/32) patients' renal function. Compared with before treatment, SCr decreased (12.08% +/- 10.11%), eGFR increased (21.14% +/- 18.55%), and ALB increased (2.76% +/- 1.97%) at the end of 3-month treatment (all P < 0.05). As for TCM syndrome factor integrals, compared with before treatment, the integrals for qi deficiency syndrome, blood deficiency syndrome, and yin deficiency syndrome decreased, while the integrals for dampness heat syndrome and turbid toxin syndrome increased (all P < 0.05). There was no obvious difference in all indices except the integral for hypertensive renal damage patients of yin deficiency syndrome (P > 0.05). The SCr decreasing percent was 19.82% +/- 8.30% for patients of non-QBDS and 5.24% +/- 10.75% for patients of QBDS. The latter was higher with statistical difference (P < 0.05). As for TCM syndrome factor integrals, the integral differences of qi deficiency and blood deficiency were obviously higher in patients of QBDS, when compared with patients of non-QBDS (P < 0.05). CONCLUSION: AAM could improve the renal function of CKD patients, elevate their ALB levels, and ameliorate associated qi deficiency syndrome, blood deficiency syndrome, and yin deficiency syndrome, especially for CKD patients of QBDS. PMID- 25137840 TI - [Effect of Chinese herbal therapy on T-lymphocytes of IgA nephropathy patients: a clinical observation]. AB - OBJECTIVE: To observe the effect of Chinese herbal therapy on T-lymphocyte subsets in patients with IgA nephropathy (IgAN). METHODS: Totally 36 inpatients and outpatients at Department of Nephropathy, Xiyuan Hospital, China Academy of Chinese Medical Sciences, from June 2011 to June 2013 were recruited in the treatment group, while 20 volunteers were recruited as the healthy control group. Patients in the IgAN group only took Chinese herbal decoctions by syndrome typing for 3 months (except those accompanied with hypertension additionally took antihypertensive agents such as angiotensin-converting enzyme inhibitor and/or dihydropyridines calcium antagonist). No intervention was performed in the healthy control group. The values of Th1, Th2, and CD4+ CD25+ Treg, and red blood cell number in urine were detected using flow cytometry before and after treatment. 24 h urine protein was detected using inmmunoturbidimetry. RESULTS: Compared with the healthy control group, the CD4+ CD25+ Treg level obviously decreased in the IgAN group, showing statistical difference (P < 0.01). In the IgAN group, Th1, 24 h urine protein, and urine red blood cell counts were obviously lower after treatment, showing statistical difference when compared with before treatment (all P < 0.05). CONCLUSION: Chinese herbal therapy could reduce urine erythrocyte number and 24 h urine protein of IgAN patients, and down regulating Th1 expression might be its mechanism. PMID- 25137841 TI - [Clinical analysis of syndrome-relative biological indices in acute lacuna encephalon infarction patients of upper hyperactivity of Gan Yang syndrome]. AB - OBJECTIVE: To analyze and summarize changes of syndrome-related biological indices in acute lacuna encephalon infarction patients of upper hyperactivity of Gan yang syndrome (UHGYS), thus providing objective evidence for syndrome typing and disease identification. METHODS: Recruited were 50 patients at Department of Encephalopathy, Xiyuan Hospital, China Academy of Chinese Medical Sciences, who were in line with diagnostic criteria of UHGYS as the experimental group in this study. Another 40 healthy volunteers were recruited as the control group from May 2010 to July 2012. Blood routines (including WBC, RBC, Hb, NEUT%, and LY%), hepatic and renal functions tests (including ALT, AST, TBIL, TP, ALB, Cr, and BUN) were performed by automatic whole blood analyzer and colorimetric technique. The levels of fasting blood glucose, HbAlc, blood lipids (including TC, TG, HDL C, LDL-C, and VLDL-C), and coagulation functions (including AT-III, PT, PTA, INR, TT, APTT, and FBG, reaction time), renin, angiotensin II, hs-CRP, and Hcy were also measured. The thyroid functions (including FT3, FT4, T3, T4, and TSH) were detected by electrochemiluminescence immunoassay. The levels of tumor necrosis factor alpha (TNF-alpha), IL-6 and IL-1 in serum were measured by ELISA and radioimmunoassay respectively. RESULTS: Compared with the control group, RBC, LY%, ALT, TP, ALB, HDL-C, AT-III activities, contents of PTA and FT4 obviously decreased, TBIL, BUN, Glu, HbAlc, TSH, hs-CRP, renin, Ang II, TNF-alpha, IL-1 and IL-6 significantly increased in the experimental group (P < 0.05, P < 0.01). CONCLUSION: The pathological process of acute lacuna encephalon infarction patients of UHGYS was closely correlated with thyroid functions, the renin angiotensin-aldosterone system, the extrinsic and intrinsic coagulation systems, as well as inflammation reaction. PMID- 25137842 TI - [Effect of acupuncture-anesthetic composite anesthesia on the incidence of POCD and TNF-alpha, IL-1beta, IL-6 in elderly patients]. AB - OBJECTIVE: To explore the effect of acupuncture-anesthetic composite anesthesia (AACA) on the incidence of postoperative cognitive dysfunction (POCD) and changes of TNF-alpha, IL-1beta, and IL-6 in elderly patients. METHODS: Totally 83 patients undergoing surgical resection of gastrointestinal tumor were randomly assigned to the simple anesthesia group (A group, 41 cases) and the AACA group (B group, 42 cases). Patients in Group A received endotracheal general anesthesia. Those in Group B were induced by acupuncture anesthesia for 30 min by needling at Baihui (DU20), Neiguan (PC6), Zusanli (ST36). The electro-acupuncture (EA) apparatus was connected after arrival of qi, with the wave pattern of density 2/100 Hz. The stimulus intensity was set by patients' tolerance, with the peak current of 5 mA. Then the endotracheal general anesthesia was performed and the EA lasted till the end of the surgery. The cognitive function of all patients was assessed before operation and at day 3 after operation using mini-mental state examination (MMSE). POCD was confirmed if with one or more decreased stand- ard. The peripheral venous blood was collected before anesthesia induction (TO), immediately at the end of surgery (T1), 24 h after operation (T2), and 48 h after operation (T3), and serum concentrations of IL-1beta, IL-6, and TNF-alpha were correspondingly measured using ELISA. RESULTS: The postoperative anesthesia awakening time was shorter in Group B than in Group A [(20.37 +/- 6.09) min vs (29.24 +/- 7.48) min, P < 0.05]. The remifentanil dose used during the operation was less in Group B than in Group A (P < 0.05). The incidence of POCD at day 3 was lower in Group B than in Group A [10/41 (23.8%) vs 15/42 (36.5%), P < 0.05]. The concentrations of IL-1beta, IL-6, and TNF-alpha at T1-T3 were higher than those at TO in the two groups (P < 0.05). The increment of TNF-alpha and IL-1beta was less in Group B than in Group A (P < 0.05). CONCLUSION AACA could reduce the incidence of POCD and inhibit postoperative release of TNF-alpha, IL-1beta, and IL-6 in elderly patients undergoing colorectal cancer resection. PMID- 25137843 TI - [Jiawei shentong zhuyu decoction prevented the occurrence of failed back surgery syndrome and its effect on serum TNF-alpha a clinical study]. AB - OBJECTIVE: To explore the clinical roles of Jiawei Shentong Zhuyu Decoction (JSZD) in preventing the occurrence of failed back surgery syndrome (FBSS), and to observe its effect on serum tumor necrosis factor-alpha (TNF-alpha). METHODS: Totally 100 patients prepared for surgical operation due to lumbar intervertebral disc herniation were randomly assigned to the treatment group and the control group according to random number table, 50 cases in each group. Patients in the treatment group additionally took JSZD, one dose per day, taken in two portions, once in the morning and once in the evening. Those in the control group took Celecoxib Capsule (200 mg each time, once per day) and Mecobalamin Tablet (0.5 mg each time, 3 times per day). They only took Mecobalamin Tablet from the 11th day. All patients were treated for 30 days. Japanese Orthopaedic Association (JOA) score was performed before treatment, at week 1, after treatment, at 6 months of followed-ups, and at 12 months of followed-ups. And the levels of TNF-alpha in the peripheral blood were observed before treatment and at one month after treatment. RESULTS: Totally 93 patients completed the followed-up study. The JOA scores were improved after treatment, at 6 and 12 months of followed-ups (P < 0.05, P < 0.01). The JOA score at 6 months of followed-ups was superior in the treatment group to that of the control group (P < 0.05). Five patients (accounting for 10.6%) suffered from FBSS in the treatment group, while 9 (accounting for 19.6%) suffered from FBSS in the control group. The treatment group was superior to the control group (P < 0.05). The TNFalpha level was improved after treatment in the two groups. Of them, the improvement of TNF-alpha in the treatment group was better than that of the control group (P < 0.05). CONCLUSION: The application of JSZD was effective for preventing the occurrence of FBSS, and improved the serum TNF-alpha level. PMID- 25137844 TI - [Effect of application of acupuncture-anesthetic composite anesthesia on hysteroscopic surgery: a clinical study]. AB - OBJECTIVE: To observe the analgesic effect and safety of acupuncture-anesthetic composite anesthesia (AACA) in hysteroscopic surgery. METHODS: Totally 93 patients undergoing hysteroscopic surgery were randomly assigned to the intravenous anesthesia group (A group, 30 cases), the AACA group (B group, 32 cases), and the acupuncture combined with intravenous anesthesia group (C group, 31 cases). Patients in Group A were anesthetized by sufentanil combined propofol. Those in Group B were anesthetized by sufentanil combined acupuncture. Those in Group C were anesthetized by sufentanil, propofol combined acupuncture. Yinlian and Ququan (LR8) were needled for patients in Group B and C. The peri-operative mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2), the surgical time, the recovery time, the sufentanil and propofol dosages, adverse anesthesia reactions were observed. Meanwhile, the OAA/S score, Ramsay sedation score, and Visual Analogue Score (VAS) were also measured. RESULTS: Compared with Group A and C, patients in Group B were awake, with obvious increased OAA/S score (P < 0.01). Ramsay sedation score was significantly lower (P < 0.01).The MAP and HR were elevated (P < 0.05). The patient case of SpO2 less than 85% during the operation decreased (P < 0.05). The incidence of postoperative dizziness was reduced (P < 0.05). Compared with Group A, the propofol consumption decreased in Group C (P < 0.05). There was no statistical difference in the operation time, the sufentanil dosage, VAS score, the incidence of postoperative nause- a and vomiting among the three groups (P > 0.05). CONCLUSIONS: The patients were awake in AACA. The intraoperative sedation was better than that obtained by intravenous anesthesia. But the analgesic effect was similar to that obtained by intravenous anesthesia. PMID- 25137845 TI - [Treatment of chronic heart failure of Xin-Shen yang deficiency, interior retention of water-fluid syndrome by external application of Zhuangshenling recipe combined with western medicine: a clinical study]. AB - OBJECTIVE: To observe the effect of external application of Zhuangshenling Recipe (ZR) combined with Western medicine (WM) on the heart function of chronic heart failure (CHF) patients of Xin-Shen yang deficiency, interior retention of water fluid syndrome (XSYDIRWFS). METHODS: Totally 140 CHF patients of XSYDIRWFS were randomly assigned to two groups, the treatment group and the control group, 70 in each group. All patients received WM therapy. Those in the treatment group were applied with ZR at Xinshu (BL15) and Shenshu (BL23), while those in the control group were applied with placebos at Xinshu (BL15) and Shenshu (BL23). The therapeutic course for all was 12 weeks. The integrals of TCM syndrome, grading of cardiac function, brain natriuretic polypeptide (BNP), and 6 min walking distance were observed before and after treatment. RESULTS: After twelve weeks of treatment, the effective rate of improved grading of cardiac function, the total effective rate of TCM syndrome efficacy, and the BNP level were obviously better in the treatment group (P < 0.05). There was no statistical difference in 6 min walking distance between the two groups (P > 0.05). CONCLUSION: External application of ZR combined with WM could improve the heart function of CHF patients of XSYDIRWFS. PMID- 25137846 TI - [Effect of Chinese drugs for Pi strengthening Shen benefiting on the immunity function of HIV patients' specific T cells]. AB - OBJECTIVE: To explore the effect of Chinese drugs for Pi strengthening Shen benefiting (CDPSSB) on the immunity function of HIV/AIDS patients' specific T cells. METHODS: Totally 20 patients were randomly recruited from the treated group [treated by CDPSSB combined highly active anti-retroviral therapy (HAART)] and 23 patients were randomly recruited from the control group (treated by HAART alone). All patients were follow-up infected persons form You'an Hospital between from June 2010 to June 2012. CD4+ T absolute counts and HIV viral load were detected. Meanwhile, HIV whole gene overlapping peptides were used as stimulating antigen. The response intensity of HIV specific T cells was detected in the two groups. RESULTS: There was no statistical difference in CD4 T absolute counts or HIV viral load between the two groups (P > 0.05). The response intensity of HIV specific T cells was significantly enhanced in the treated group, when compared with the control group (P < 0.05). Along with elongation of treatment time (6, 12, 18, and 24 months) in the treated group, the response intensity of HIV specific T cells showed enhancing tendency, but there was no statistical difference among these time points (P > 0.05). CONCLUSION: CDPSSB could enhance improve the immunity function of HIV specific T cells, which might be one of its mechanisms. PMID- 25137847 TI - [Analysis of tongue figure features in 990 cases of sexually transmitted and intravenous drug use spread HIV infected population in Xinjiang]. AB - OBJECTIVE: To investigate the tongue manifestation features of sexually transmitted and intravenous drug use spread HIV infected population in Xinjiang. METHODS: Recruited were 990 HIV infected subjects in Xinjiang from May 2011 to March 2012, who were assigned to the intravenous drug use spread HIV infected (498 cases) and the sexually transmitted (492 cases). By using tongue figure shoot combined with analyses of experts, tongue manifestations were analyzed and compared between the sexually transmitted and the intravenous drug use spread from four aspects, i.e., the tongue color, the tongue shape, the fur color, and the fur property. RESULTS: Compared with the sexually transmitted population, red tongue, fissured tongue, yellow fur, thick fur, eroded fur, deficiency of fur fluid were more often seen, showing statistical difference (P < 0.05). Compared with the intravenous drug use spread population, pale tongue, white fur, and thin fur were more often seen, showing statistical difference (P < 0.05). CONCLUSIONS: The tongue manifestations of the intravenous drug use spread HIV population reflected inner exuberance of evil toxin and heat impairing qi and yin. Compared with the intravenous drug use spread population, the attack of HIV infection was more hiding in the sexually transmitted population, with milder internal injury. Their Wei-qi was not damaged and no obvious change occurred in the tongue figure. PMID- 25137848 TI - [Effect of compound qingqin liquid on the expression levels of ang II and COX-2 mRNA transcription and protein expression in the renal tissue of uric acid nephropathy rats: an experimental study]. AB - OBJECTIVE: To investigate the effect of Compound Qingqin Liquid (CQL) on the expression level of angiotensin II (Ang II) and COX-2 mRNA transcription and protein expression in the renal tissue of rats with uric acid nephropathy. METHODS: SD rats were randomly divided into the blank control group, the model group, the positive drug group, the high, moderate, and low dose CQL group according to number randomization principle. The model was established by gastrogavage of adenine, accompanied with yeast feeding. Distilled water was given by gastrogavage to rats in the blank control group and the model group. Allopurinol at the daily dose of 9.33 mg/kg was given by gastrogavage to rats of the positive control group. CQL at the daily dose of 3.77 g/kg, 1.89 g/kg, and 0.09 g/kg was respectively given by gastrogavage to rats in the high, moderate, and low dose CQL groups. All treatment lasted for 6 weeks. Rats were randomly divided at week 4 (3 in the blank control group, and 6 in the rest groups), and the rest rats were killed at week 6. The renal tissue was extracted. The expression level of Ang II and COX-2 mRNA transcription were detected by RT-PCR. The expression level of Ang II was detected by ELISA. The expression level of COX 2 protein was detected by Western blot and immunohistochemical assay. RESULTS: Compared with the blank control group, except the mRNA expression of Ang II at week 4, the mRNA and protein expression of Ang II and COX-2 obviously increased at week 4 and 6 in the model group (P < 0.01, P < 0.05). The COX-2 protein expression at week 4 was obviously lower in the high and moderate dose CQL groups than in the model group and the low dose CQL group (P < 0.05); the average integral of optical density value was obviously lower in the positive control group than in the model group. Except the mRNA expression of Ang II in the high dose CQL group at week 6, the mRNA and protein expression of Ang II obviously decreased in the positive control group and each dose CQL group (P < 0.01, P < 0.05). Of them, the effects were better in the high and moderate dose CQL groups than in the positive control group and the low dose CQL group (P < 0.05, P < 0.01). Besides, the mRNA expression of COX-2, the average integral of optical density value were obviously lower in the positive control group and each dose CQL group than in the model group (P < 0.05). The protein expression of COX-2 was obviously lower in the high and moderate dose CQL groups than in the model group (P < 0.05). Of them, the mRNA expression of COX-2 was better in the moderate dose CQL group than in the positive control group (P < 0.05); the protein expression of COX-2 was better in the high dose CQL group than in the low dose CQL group (P < 0.05). CONCLUSION: CQL was capable of lowering the expression level of Ang II, COX-2 mRNA transcription and protein expression, thus suppressing the inflammatory pathological injury of the renal tissue. PMID- 25137849 TI - [Renal protection of Tangke Decoction on rats with diabetes and its effect on the expression of TGF-beta1/Smad4]. AB - OBJECTIVE: To observe the effect of Tangke Decoction (TD) on the expression of TGF-beta1/Smad4 of rats with early diabetes and to explore the effect and mechanism of TD against the renal injury induced by diabetes. METHODS: SD rats were randomly divided into the normal control group (n = 12), the model group (n = 10), the Chinese herbs prevented group (n =10), the Chinese herbs treated group (n = 10), and the Western medicine control group (n = 10). TD (18 mg/kg) was given by gastrogavage to rats in the Chinese herbs prevented group immediately after successful modeling for 12 weeks, once daily. At the 4th week of successful modeling, rats in the rest 4 groups were administered by gastrogavage. Equal volume of normal saline was given to rats in the model group and the normal control group. Benazepril suspension (1 mg/kg) was administered by gastrogavage to rats in the Western medicine control group for 8 weeks, once daily. TD (18 mg/kg) was given by gastrogavage to rats in the Chinese herbs treated group for 8 weeks, once daily. The body weight, kidney weight, index of kidney weight, fasting blood sugar, 24 h urinary albumin excretion rate were examined after experiment. The pathological changes of the renal tissue were observed by HE staining, Masson staining, and electron microscope. The expression of renal transforming growth factor-beta1, (TGF-beta1) and Smad4 were detected using immunohistochemical assay. RESULTS: Compared with the normal control group, the body weight of rats decreased significantly; the kidney weight, index of kidney weight, blood sugar, 24 h urinary protein excretion, the urinary albumin excretion rate,TGF-beta1 and Smad4 expression increased significantly in the model group (all P < 0.01). Compared with the model group, the aforesaid indices were improved in each treatment group with statistical difference (P < 0.05, P < 0.01). Compared with the Western medicine control group, the kidney weight, index of kidney weight, blood sugar, 24 h urinary protein excretion, and the urinary albumin excretion rate were obviously improved in the Chinese herbs prevented group (P < 0.01). The renal pathological changes were most obvious in the model group significantly, but they were improved in all treatment groups. CONCLUSION: TD could obviously improve the symptoms of diabetes and down-regulate the expression of renal TGF-beta1 and Smad4 of early diabetic nephropathy rats, which suggested that TD had certain preventive effect on early diabetic nephropathy. PMID- 25137850 TI - [Ginkgo biloba extract 50 inhibited beta-amyloid-induced oxidative stress in rats' hippocampal neurons: an experimental study]. AB - OBJECTIVE To study the in vitro effect and mechanism of Ginkgo biloba Extract 50 (GBE50) for inhibiting beta-amyloid (Abeta)-induced oxidative stress in rats' hippocampal neurons. METHODS: The primary hippocampal neurons were cultured in vitro and divided into 4 groups, i. e. the normal control group (Ctrl), the Abeta group, the propanediol control group (PDO), and the six GBE50 concentrations groups (5, 10, 25, 50, 100, and 200 microg/mL). Excepted the Ctrl group, neurons were induced to oxidative stress by 20 gmolLAbeta25-35. The MTT and fluorescent probes labeling were used to observe the effect of GBE50 with different concentrations on the cell viability and the generation of intracellular reactive oxygen species (ROS) in neurons. Furthermore, Western blot was used to detect the cytoplasmic/total cytochrome C (Cyto C) ratio and total intracytoplasmal Cyto C, and the effect of the expression of oxidative stress-related protein Cyto C and activated Caspase-3 in three GBE50 concentrations groups (25, 50, and 100 microg/mL). RESULTS: Compared with the Ctrl group, the cell vitality was obviously lowered and intracellular ROS generation significantly increased after induction of 20 micromol/L Abeta25-35 (both P < 0.05). Compared with the Abeta group, the cell vitality was evidently improved after treated with different GBE50 doses. Except for 10 microg/mL, the cell vitality could be obviously elevated along with increased drug concentrations (P < 0.05). Meanwhile, the intracellular ROS generation decreased significantly in each GBE50 dose groups (P < 0.05). Abeta could increase the cytoplasmic/total Cyto C ratio and enhance the activated Caspase-3 expression significantly (P < 0.05). Compared with the Abeta group, among the three concentrations of GBE50, the Cyto C ratio was obviously lowered in the 100 microg/mL GBE50 group (P < 0.05), and the expression of activated Caspase-3 significantly decreased in 50 microg/mL and 100 microg/mL GBE50 groups (P < 0.05). CONCLUSIONS : 20 micromol/L Abeta25-35 could induce the generation of intracellular ROS in hippocampal neurons. GBE50 could inhibit Abeta induced intracellular oxidative stress of neurons through lowering the cytoplasmic/total Cyto C ratio and inhibiting the activation of apoptosis protein Caspase-3 expression. PMID- 25137851 TI - [Effect of advanced glycation end products on the function and angiogenesis of adipose tissue-derived stem cells and the protective effect of danhong injection: an experimental study]. AB - OBJECTIVE To investigate the effect of Nepsilon-(carboxymethyl) lysine albumin (CMLs), a primary advanced glycation end products (AGEPs) isoform in diabetic body, on the function and angiogenesis of adipose tissue-derived stem cells (ADSCs) and the protective effect of Danhong Injection (DH). METHODS Human ADSCs were cultured and separated from human subcutaneous fatty tissue using enzymatic digestion and centrifugation. The morphology was observed using optical microscope and differentiation capacities assessed. Cells were exposed to 5 different interventions respectively for 24 h, i.e., PBS, 60 1 microg/mL BSA, 60 microg/mL CML-BSA, 100 microL/mL DH, and 60 micro./mL CML-BSA +100 microL/mL DH. Their effect on the proliferation, migration, apoptosis, and secretion were observed using WST-1 assay, Transwell assay, Annexin V-FITC/PI flow meter test reagent kit, human VEGF reagent kit, ELISA reagent kit, respectively. The effect on ADSCs angiogenesis was observed by in vitro angiogenesis test. RESULTS: Compared with the BSA group, the capacities of proliferation and migration could be significantly inhibited by CML-BSA, the apoptosis promoted, the secretion of VEGF reduced, and the angiogenesis of ADSCs weakened (P < 0.05). Compared with the blank control group, 100 microL/mL DH could significantly promote the proliferation and migration capacities of ADSCs, inhibit apoptosis of ADSCs, increase the secretion of VEGF, and improve the angiogenesis of ADSCs (P < 0.05). Compared with the CML-BSA group, the inhibition of CML-BSA on the proliferation and migration capacities of ADSCs could be significantly reversed, the promotion of CML-BSA on the apoptosis of ADSCs improved, the secretion of VEGF increased, and the angiogenesis of ADSCs elevated (P < 0.05). CONCLUSION: clusion CMLs could significantly inhibit the proliferation and migration capacities of ADSCs, promote their apoptosis, and inhibit their angiogeneses, which could be improved by DH. PMID- 25137852 TI - [Effect of zhenqing recipe on non-alcoholic fatty liver in type 2 diabetes rats and the expression of SIK1]. AB - OBJECTIVE: To observe the effect of Zhenqing Recipe (ZQR) on non-alcoholic fatty liver (NAFL), and the expression of hepatic salt-inducible kinase 1 (SIK1) and sterol-regulatory element binding protein-ic (SREBP-lc) in type 2 diabetes rats. METHODS: A rat model of type 2 diabetes was established by high fat/sucrose diet combined with intraperitoneal injection of small dose streptozotocin (STZ) . Modeled rats were randomly divided into the model group, the ZQR group, and the metformin group, 8 in each group. Eight rats were recruited as a normal control group. ZQR at the daily dose of 12 g crude drugs/kg was administered to rats in the ZQR group by gastrogavage. Metformin suspension at the daily dose of 150 mg/kg was administered to rats in the metformin group by gastrogavage. Equal volume of distilled water was administered to rats in the normal control group and the model group. All medication lasted for 12 weeks. The levels of fasting blood glucose (FBG), free fatty acid (FFA), serum triglyceride (TG), serum total cholesterol (TC), serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were detected. The body weight and wet liver weight were weighed, and the liver weight index calculated. The liver TG content was measured. The pathological changes of liver and the expression of SIK1 were observed by HE staining and immunohistochemistry. The mRNA and protein expression of SIK1 and SREBP-1c were detected using RT-PCR and Western blot. RESULTS: Compared with the normal control group, FBG, FFA, TG, TC, ALT, AST, liver weight index, and liver TG contents significantly increased (P < 0.01); liver steatosis was severe, the mRNA and protein expression of SIK1 obviously decreased (P < 0.01); mRNA and protein expression of SREBP-1c increased (P < 0.01). After drug therapy, compared with the model group, FBG, FFA, TG, TC, ALT, AST, and liver weight index significantly decreased, liver TG contents significantly decreased, the mRNA and protein expression of SIK1 obviously increased, while mRNA and protein expression of SREBP-1c obviously decreased (P < 0.05, P < 0.01) in the ZQR group and the metformin group (P < 0.05, P < 0.01); and the pathological changes were also improved. All the indices were improved more in the ZQR group (all P < 0.05). CONCLUSION: In this experiment, we found that the expression of SIK1 decreased in NAFL rats with type 2 diabetes. ZQR could alleviate lesion of NAFL type 2 diabetes rats possibly by up-regulating hepatic SIK1 expression at mRNA and protein levels. PMID- 25137853 TI - [Effect of Mudan Granule on islets beta cell function in monosodium glutamate induced obese mice with insulin resistance: an experimental study]. AB - OBJECTIVE: To study the effect of Mudan Granule (MD) on the glucose metabolism and beta cell function in monosodium glutamate (MSG) induced obese mice with insulin resistance (IR). METHODS: MSG obese mice were induced by subcutaneous injecting MSG (4 g/kg for 7 successive days in neonatal ICR mice). Forty MSG mice with IR features were recruited and divided into four groups according to body weight, fasting blood glucose, triglyceride (TG), total cholesterol (TC), and the percentage of blood glucose decreased within 40 min in the IR test, i.e., the model group (Con), the low dose MD group, the high dose MD group, and the Metformin group (Met). Besides, another 10 ICR mice were recruited as the normal control group (Nor). The water solvent of 2.5 g/kg MD or 5 g/kg MD was respectively administered to mice in the low dose MD group and the high dose MD group. Metformin hydrochloride was given to mice in the Met group at 0.2 g/kg body weight. Equal dose solvent distilled water was administered to mice in the Nor group and the Con group by gastrogavage, once per day. All medication was lasted for 15 weeks. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were performed after 6 weeks of treatment. Beta cell function was assessed by hyperglycemic clamp technique. The morphological changes in the pancreas were evaluated by hematoxylin-eosin (HE) staining. Changes of iNOS, NF-kappaB p65, and p-NF-kappaB p65 in the pancreas were tested. RESULTS: Compared with the Nor group, the blood glucose level, AUC, and fasting blood insulin, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, pNF-kappaB p65 subunit obviously increased; decreased percentage of blood glucose within 40 min in ITT, glucose infusion rate (GIR), Clamp 1 min insulin, and Max-Insulin obviously decreased in the Con group (P < 0.05, P < 0.01). Compared with the Con group, the aforesaid indices could be improved in the Met group (P < 0.05, P < 0.01). In the low dose MD group, AUC, iNOS activities, and the expression of iNOS and p-NF-kappaB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT and GIR obviously increased (P < 0.05, P < 0.01). In the high dose MD group, AUC, ONOO-contents, iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, and p-NF-KB p65 subunit obviously decreased; percentage of blood glucose within 40 min in ITT, Max-Insulin, and GIR obviously increased (P < 0.05, P < 0.01). CONCLUSION: MD could significantly improve IR and functional disorder of 3 cells in MSG obese mice, which might be associated with lowering inflammatory reaction in the pancreas. PMID- 25137854 TI - [Roles of TRPV1 receptor in electroacupuncture regulating the jejunal motility of mice: an experimental study]. AB - OBJECTIVE: To observe the intestinal movement of transient receptor potential vanilloid 1 or vanilloid receptor 1 (TRPV1) knockout mice after stimulated by electroacupuncture (EA), and to primarily explore the roles of TRPV1 receptor in the jejunal motility regulated by acupuncture. METHODS: Normal wild-type CL57BL/6 and TRPV1 gene knockout mice were recruited in two groups, the B6 group and the TRPV1 group, 15 in each group. The thermal threshold and the mechanical pain threshold were respectively detected using JL-F digital photo thermal analyzer instrument and ALMEMO2450 machine. The difference between the two thresholds were compared. Meanwhile, a self-made pressure head was placed in the jejunum. The internal pressure was monitored. When the pressure was stable, 2 mA 2/15 Hz EA at Quchi (LI11), Tianshu (ST25), Shangjuxu (ST37), and Dachangshu (BL25) to observe the changes of intestinal pressure value between before and after EA. The curve of internal pressures was recorded. RESULTS: (1) The stimulation of light/heat and mechanical stimulation were obviously slowed in the TRPV1 group than in the B6 group (P < 0.01). (2) In the intestinal pressure observation experiment, the bowel movement was not obviously seen in the two groups when acupunctured at Quchi (LI11) and Shangjuxu (ST37) (P > 0.05). (3) Acupuncture at Tianshu (ST25) and Dachangshu (BL25) of TRPV1 knockout mice could lead to intestinal movement (P < 0.05), mainly inhibited bowel movement. The changing degree was equivalent to that of B6 mice. CONCLUSIONS: Under the physiological condition, TRPV1 might be mediated by thermal and mechanical stimulation. But TRPV1 mediated acupuncture effect was quite complex, indicating TRPV1 mice might be one of intestinal movement mediating factors. PMID- 25137856 TI - [A blind technique used in randomized controlled trials of treatment based on changes of syndromes]. AB - Treatment based on syndrome differentiation is an essential feature of traditional Chinese medical diagnosis. The interventions based on changes of syndrome types in randomized controlled trials are complicated, leading to the difficulty of blind method enforcement. This article described a double-blind method. It could be used in randomized controlled trials under the condition of different syndrome types and different medications. It numbered drugs in two stages, and in two phases to achieve double-blind. This method not only guaranteed investigators and subjects to be in blinded conditions, but also achieved using different medications for patients of different syndromes. It also caused no drug waste. It was scientific and feasible. PMID- 25137855 TI - [Prevention of Inonotus obliquus polysaccharides for high power microwave radiation induced testicular injury in rats: an experimental research]. AB - OBJECTIVE: To investigate the effect of Inonotus obliquus polysaccharides on testicular injury induced by exposure to high power microwave (HPM) in rats. METHODS: A total of 30 male Wistar rats were randomly divided into 5 groups, i.e., the normal control group, the microwave radiation model group, the treatment group, the new microwave radiation model group, and the prevention group, 6 in each group. All rats, except those in the normal control group, were exposed to microwave at an average power density of 200 mW/cm2 for 6 min. Rats in the control group and the model group were administered with normal saline by gastrogavage, once a day. Rats in the treatment group and the prevention group were given with Inonotus obliquus polysaccharides by gastrogavage, 2 mL each time (400 mg/kg body weight), once a day. All rats were sacrificed on the 11th day.The sperm density and the rate of sperm deformity were determined. Pathological changes of testis were observed by light microscope and transmission electron microscope. RESULTS: Short-term HPM irradiation could significantly reduce the sperm density and increase the sperm deformity rate (P < 0.05). Meanwhile, obvious pathological changes of testes occurred. Compared with the two model groups, the sperm density increased and the sperm deformity rate decreased in the treatment group and the prevention group (P < 0.05). Under the light microscope, injuries of spermatogenic cells and stromal cells, as well as vascular dilatation and congestion were obviously alleviated in the treatment group and the prevention group. Mitochondrial swelling and endoplasmic reticulum expansion shown by ultrastructural observation were also significantly alleviated. Of them, injuries of spermatogenic cells and inflammation response were milder in the treatment group than in the prevention group. CONCLUSIONS: Inonotus obliquus polysaccharides had significant protective effect on microwave radiation induced testicular injury. Better effect was obtained by therapeutic medication than preventive medication. PMID- 25137857 TI - [The application principle and strategies of transliteration in English translation of Chinese medicine]. PMID- 25137858 TI - [The effectiveness and mechanism of Chinese medicine and pharmacy in intervening myocardial fibrosis]. PMID- 25137859 TI - [An overviewn of integrative medical research of heart failure patients with normal ejection fraction]. PMID- 25137860 TI - Preoxygenation-routine preoxygenation during induction and recovery from anesthesia is recommended as a minimal safety precaution. PMID- 25137861 TI - Fentanyl-induced cough--pathophysiology and prevention. AB - Many reports have demonstrated that intravenous administration of a bolus of fentanyl at induction of anesthesia can cause coughing with varying degrees. This cough can be benign, but sometimes it causes undesirable side effects including an increase in intraabdominal, intracranial or intraocular pressure. Many studies demonstrated that the incidence and severity of fentanyl-induced cough could be related to age, ethnicity, history of smoking, as well as to the rate, route, dose and concentration of fentanyl administered. This cough was described by several mechanisms including an inhibition of central sympathetic system leading to vagal predominance, reflex bronchonstriction after the stimulation of tracheobronchial tree receptors, or histamine release. The efficacy of several measures to avoid fentanyl-induced cough have been demonstrated, and several anesthetics adjuncts can be given prior to fentanyl administration aiming at decreasing this unwanted side effect. PMID- 25137862 TI - Cerebral "hyperoxygenation" with inhalational induction of anesthesia in children: a retrospective comparison between vasoparalytic sevoflurane vs. vasoneutral fentanyl. AB - BACKGROUND: The higher levels of oxygen in cerebrum may contribute to neuro apoptosis, analogous to direct tissue injury induced by toxic levels of oxygen. Earlier report highlighted the possibility of cerebral "hyperoxygenation" secondary to inhalational induction of anesthesia with sevoflurane in small number of children. OBJECTIVE: The aim of this retrospective review was whether similar cerebral "hyperoxygenation" trends can be seen in larger and retrospective patients' database. METHODS: Data of patients who had undergone cardiac surgeries at Children's Hospital during the two-year period (2010-2011) was retrieved during this retrospective review: (a) stored computer data from INVOS Cerebral/Somatic Oximeter for oximetry numbers and total duration of oximetry monitoring, (b) paper chart perfusion records of the cardiac surgeries for age and sex of the patient, urgency of the surgery, type of induction (inhalational or intravenous), and total duration of cardiopulmonary bypass, (c) general medical records for inpatient setting vs. outpatient setting of the patient, and (d) anesthesia medical records for name of the medications used during induction of anesthesia to segregate the patients who had fentanyl as a lone induction agent and sevoflurane as a lone induction agent, for final statistical calculations and analysis. For the two-year period (2010-2011), data of 358 patients who had cardiac surgeries at Children's Hospital were reviewed. However, after deletions of various patients' data due to various reasons, only 69 patients (0-4 years of age) who had sevoflurane induction were analyzed for final statistical comparisons to 14 patients (0-4 years of age) who had fentanyl induction. RESULTS: Cerebral and renal "hyperoxygenation" occurred during the first 127 minutes with sevoflurane as compared to fentanyl though the percentage changes from pre-induction values in oximetry during this time did not reach level of significance. However, only cerebral "hyperoxygenation" persisted in the last 127 minutes when patients had been induced with sevoflurane as compared to fentanyl. CONCLUSION: Cerebral "hyperoxygenation" occurs with inhalational induction of anesthesia with vasoparalytic sevoflurane in children 0 to 4 years of age when compared to anesthesia induction with vasoneutral fentanyl. PMID- 25137863 TI - Comparison between intravenous patient controlled analgesia and patient controlled epidural analgesia in cirrhotic patients after hepatic resection. AB - BACKGROUND: Postoperative pain is one of the most important problems that confront surgical patients. The aim of this work is to compare pain control using intravenous patient controlled analgesia (PCA) and patient controlled epidural analgesia (PCEA) in cirrhotic patients undergoing elective hepatic resection. METHODS: Thirty four adult patients ASAI and II scheduled for liver resection were randomly allocated into two groups-Group (P) with I.V (PCA) with fentanyl and Group (E) (PCEA) via epidural catheter using Bubivacaine 0.125% plus 2 microgram per ml fentanyl. Coagulation changes were followed and pain score was compared in both groups. RESULTS: 34 child A cirrhotic patients, undergoing liver resection were studied. The demographic data were comparable in both groups. There was a significant decrease in pain score in both groups during the follow up period when compared to their initial score. When comparing average pain score between both groups, the PCEA group had significantly lower values. The changes in prothrombin time (PT), INR, and hemoglobin (Hb), were significant all over the follow up period compared to their corresponding base line values. 2 cases needed FFP to normalize the INR for epidural removal. There was no significant difference regarding postoperative nausea and vomiting (PONV) in both groups, no clinical manifestation suggesting epidural hematoma, and no cases were recorded to have respiratory depression. There were no significant differences in patient satisfaction and ICU stay. CONCLUSION: The two modalities of pain control seems to be nearly equivalent, but considering the risk of epidural catheter insertion and removal in cirrhotic patients who are further exposed to hepatectomy with subsequent additional coagulopathy, it may be wise to consider IVPCA technique as a policy for pain management in cirrhotic patient undergoing hepatectomy. PMID- 25137864 TI - Simulation training in endotracheal intubation in a pediatric residency. AB - BACKGROUND: Airway management and endotracheal intubation are essential skills for pediatric residents. Simulation-based technology is used for training residents but it remains unclear whether high fidelity simulation results in better retention of skills compared to low fidelity. The study assesses high fidelity simulation of endotracheal intubation and traditional low fidelity training in improving pediatric residents' knowledge retention and technical skills; and if the difference translates into higher "real time" intubation success rates. METHODS: Second and third year pediatric residents were randomized into high fidelity (intervention) or low fidelity simulation (control) groups. Airway management and intubation skills were taught using a didactic lecture and demonstration on low fidelity mannequins. Knowledge was assessed before randomization (T0) and 6 months after training (T6). Other outcome measures were: 1) airway management and intubation skills at T6 and T12 (12 months later) and 2) successful intubation of actual patients by T12. RESULTS: 10 out of 11 residents completed the intervention. Theoretical knowledge improved for both groups. Participants made less mistakes (M) overtime: M (T0) = 3.2 and M (T6) = 2.6 for the intervention group, and M (T0) = 4 and M (T6) = 2.40 for the control. There was no significant effect of fidelity on intubation skills or the number of successful intubations recorded in logbooks (allp > 0.05). In some instances intubation skills showed regression over time. CONCLUSION: High fidelity simulation showed no impact on residents' airway management and intubation skills. Retention of theoretical knowledge persisted over time while practical skills remained at baseline or declined. PMID- 25137865 TI - A simple protocol to improve safety and reduce cost in hemodialysis patients undergoing elective surgery. AB - BACKGROUND: When patients with end-stage renal disease (ESRD) miss their routine intermittent hemodialysis (IHD), electrolyte abnormalities and volume overload often occur. An institutional protocol to ensure that patients receiving IHD have elective surgeries scheduled within 24 hours after their dialysis may reduce procedural delays or cancellations caused by hyperkalemia and hypervolemia after a missed IHD session. The effect of this protocol was evaluated. METHODS: A retrospective chart review was performed for ESRD patients receiving IHD who underwent surgery from 6 months before to 6 months after the institutional protocol was implemented. Preoperative potassium values, timing of IHD relative to surgery, and the nature of surgery (elective or emergent) were documented. The percentage of patients having IHD more than 24 hours before their elective surgery was compared before and after protocol implementation. Average potassium values were compared when IHD occurred within 24 hours vs. more than 24 hours, using t test analysis. Cost associated with delay and cancellation for IHD was also explored. RESULTS: Of the 15,799 cases performed, 190 involved ESRD patients receiving IHD. Before the protocol, 32.1% of elective cases (n = 17) involved patients scheduled for surgery more than 24 hours after IHD vs. 12.0% (n = 6) after the protocol. Preoperative potassium values were less when patients underwent IHD within 24 hours than at more than 24 hours (mean [SD], 4.32 [0.6] mEq/L vs 4.63 [0.8] mEq/L; P = .03). CONCLUSIONS: The simple scheduling policy is effective at reducing both cost and unnecessary perioperative risks for patients. PMID- 25137866 TI - Emetogenicity-risk procedures in same day surgery center of an academic university hospital in United States: a retrospective cost-audit of postoperative nausea vomiting management. AB - BACKGROUND: Despite the variable results of published studies, it is imperative for ambulatory surgery centers to self-audit local cost-implications for post operative nausea and vomiting (PONV) management. OBJECTIVE: Our retrospective cost-audit assessed if there were comparative peri-anesthesia care cost-trends among patients who had undergone Low-Emetogenicity-Risk Procedures (LERP), Moderate-Emetogenicity-Risk Procedures (MERP) and Severe-Emetogenicity-Risk Procedures (SERP). METHODS: This study was a review of Same Day Surgery Center practices in an academic university hospital setting during a three-year period (2010-2012). The patient lists were accessed from CIS and CITRIX App Bar for time audit and OR (operating room) schedule reports. Subsequently, OR pharmacy department ran a search for peri-operative anti-emetics and opioids that were billed for the patients at Same Day Surgery Center for the review period. The primary outcomes were the comparative costs/charges of these medications and comparative durations/ charges for these patients' stay in the post-anesthesia care unit (PACU). Secondary outcomes analyzed in the study included peri anesthesia durations. RESULTS: A total of 8,657 patient records were analyzed. Almost all analyzed variables revealed statistically significant inter-variable positive correlations. The patients' age was significantly (P < 0.001) different among LERP/MERP/SERP patients (LERP: 48.8 +/- 14.7 years; MERP: 61.8 +/- 14.6 years; SERP: 51.3 +/- 14.5 years). In regards to primary and secondary outcomes, the statistical significant differences among LERP/MERP/SERP patients (after correcting for both patients' age as well as patients' sex) were only achieved for preoperative times (P = 0.002; Power = 0.9), operating room recovery times (P = 0.003; Power = 0.9), PACU stay times (P < 0.001; Power = 1.0), and PACU charges (P < 0.001; Power = 1.0). CONCLUSION: PACU stay times and PACU charges were significantly higher in patients who had undergone SERP as compared to patients who had undergone LERP or MERP at our Same Day Surgery Center. PMID- 25137867 TI - The use of Airtraq laryngoscope versus Macintosh laryngoscope and fiberoptic bronchoscope by experienced anesthesiologists. AB - OBJECTIVE: The aim was to compare the hemodynamic parameters, intubation times, upper airway trauma and postoperative sore throat scores of the patients with normal airway anatomy, intubated with the Airtraq, Macintosh laryngoscope and fiberoptic bronchoscope, by experienced anesthesiologists. METHODS: Ninety patients, scheduled to undergo elective surgery under general anesthesia were randomly divided into three groups (n = 30): Group A: Airtraq laryngoscope, Group M: Macintosh laryngoscope and Group FB: fiberoptic bronchoscope. The time to intubation and success rates were recorded. The hemodynamic parameters before and one minute after the anesthesia induction were recorded and the measurements were repeated 3, 4 and 5 minutes after the endotracheal intubation. The postoperative sore throat scores and signs of any trauma were also recorded. RESULTS: Mean arterial blood pressure and heart rate were not significantly different between the three groups. The mean intubation time interval did not differ between groups. Highest postoperative sore throat scores were recorded at the 6th hour post extubation. The scores were 37.6 +/- 20.9 in Group A, 13.3 +/- 16.8 in Group M and 13.6 +/- 14.0 in Group FB. The scores in Group A were significantly higher compared to other groups. The number of patients requiring additional analgesia to relieve sore throat was also significantly higher in Group A. CONCLUSION: The Airtraq laryngoscope seems to be a more traumatic airway device in the routine endotracheal intubation compared to Macintosh laryngoscope and fiberoptic bronchoscope, when used by experienced anesthesiologists. It also does not offer advantage over the first-attempt success rates, the intubation times and hemodynamic parameters. PMID- 25137868 TI - Ultrasound-guided regional anesthesia in a pediatric patient with acute intermittent porphyria: literature review and case report. AB - Ultrasound-guided regional anesthesia techniques placed under general anesthesia have not been reported in pediatric patients with acute intermittent porphyria (AIP). A 9-year-old male with AIP presented for right inguinal herniorraphy. Family history included one relative's death after anesthesia. Preoperative preparation included reviewing medications safe for AIP patients, minimizing known AIP triggers (fasting, stress) and ensuring access to rescue medications. Intraoperative management included a propofol induction with the patient's mother present in the operating room. We performed an ultrasound-guided ilioinguinal iliohypogastric nerve block under general anesthesia. The surgery proceeded without complications and the patient did not demonstrate signs of an AIP crisis. PMID- 25137870 TI - Unusually difficult intraesophageal bougie insertion in an intubated pediatric patient. PMID- 25137869 TI - Anesthetic considerations and management of a patient with unsuspected carcinoid crisis during hepatic tumor resection. AB - Anesthetic management for massive blood loss in liver surgery concomitant with hemodynamic instability secondary to carcinoid crisis can be challenging in the perioperative setting. Hypotension, diarrhea, facial flushing, bronchospasm, and tricuspid and pulmonic valvular diseases are the common manifestations of carcinoid syndrome. This report illustrates the importance of early recognition and treatment for signs and symptoms of carcinoid syndrome not only in the preoperative setting but also in the intraoperative phase to prevent undue cardiovascular collapse. PMID- 25137871 TI - Successful intubation using McGRATH MAC in a patient with Treacher Collins syndrome. PMID- 25137872 TI - Anesthesia care providers' based interdisciplinary peri-operative cross-over post market--safety-surveillance: is it futuristic patient safety idea? Running title: post-hire PMSS for interventionists. PMID- 25137873 TI - Predictive factor for hepatic encephalopathy in cirrhotic patients who presented with acute variceal bleeding. AB - BACKGROUND: Cirrhotic patients who were hospitalized due to acute variceal bleeding and subsequently developed hepatic encephalopathy during hospital stay had dreadful outcome and high mortality rate. Recommendations regarding management and prevention of encephalopathy in these patients are not available in the current clinical practice guidelines. Defining high-risk patients could possibly prevent or early detect hepatic encephalopathy and help develop prophylactic management. OBJECTIVE: To evaluate the potential of certain clinical predictors of hepatic encephalopathy in cirrhotic patients presented with acute variceal bleeding. MATERIAL AND METHOD: The medical records of cirrhotic patients with diagnosis of acute variceal bleeding by endoscopy were retrospectively examined for clinical parameters. Potential predictive factors for hepatic encephalopathy were identified by univariate and multivariate analysis. RESULTS: One hundred seventy four cirrhotic patients who presented with acute variceal bleeding were enrolled in the present study. Hepatic encephalopathy was developed in 25 patients (14.4%). Multivariate analysis showed cirrhosis Child C, serum potassium < 3.5 mmole/L, WBC > 10,000 cells/mm3, and hemoglobin < 8 gm/dL on the day of admission were significant factors predicting hepatic encephalopathy in cirrhotic patients presenting with acute variceal bleeding (adjusted odds ratio 36.7, 9.25, 4.91, and 4.52, respectively). Cirrhotic patients presented with acute variceal bleeding who developed hepatic encephalopathy had higher rate of infection (40% vs. 5.4%), respiratory failure (20% vs. 2%), unit of red blood cell transfusion (3.8 +/- 1.8 units vs. 2.6 +/- 1.8 units), volume of fresh frozen plasma transfusion (1,000 (0-4,000) cc vs. 500 (0-5,000) cc), length of stay (9.0 +/- 3.5 days vs. 5.6 +/- 1.8 days), and mortality rate (8% vs. 0.7%), than non-hepatic encephalopathy p-value < 0.05. CONCLUSION: Cirrhotic patients presented with acute variceal bleeding with cirrhosis Child C, serum potassium < 3.5 mmole/L, WBC > 10,000 cells/mm3, and hemoglobin < 8 gm/dL were significant predictors for development of hepatic encephalopathy. Cirrhotic patients with acute variceal bleeding who developed hepatic encephalopathy had high morbidity and mortality rates. PMID- 25137874 TI - Short-term administration of an angiotensin II receptor blocker in patients with long-term hemodialysis patients improves insulin resistance. AB - BACKGROUND: Insulin resistance is commonly observed in uremic patients. Angiotensin II receptor blockers (ARB) are reported to act as insulin sensitizers in the animal model of hypertension and hypertensive patients. The authors investigated the effects of valsartan on insulin resistance and glucose metabolism in patients with long-term hemodialysis in the prospective, randomized controlled study. MATERIAL AND METHOD: Thirty-three hemodialysis patients were randomized into two treatment groups, valsartan 80 to 320 mg/day (n = 18) or non renin-angiotensin-aldosterone-system blocking antihypertensive agents (control, n = 15), treated for 12 weeks. Insulin resistance determined by homeostasis model assessment (HOMA-IR), fasting plasma glucose (FPG), fasting plasma insulin, and blood pressure monitoring were measured during the study. RESULTS: At baseline, metabolic profiles did not significantly differ between the treatment and the control groups. After 12 weeks of treatment, the valsartan group significantly improved HOMA-IR from 2.6 +/- 0.9 to 2.3 +/- 0.7 (p = 0.041) and significantly decreased FPG from 90.1 +/- 15.1 to 84.8 +/- 13.2 mg/dL (p = 0.008). In contrast, the control group was not associated with any significant changes in HOMA-IR, FPG, and fasting insulin levels. At the end of 12-week treatment, HOMA-IR, FPG, and fasting insulin levels were not significantly different between the two groups. CONCLUSION: These results indicate that the antihypertensive action of valsartan improves glucose metabolism by improving the peripheral insulin sensitivity in subjects with long-term dialysis. PMID- 25137875 TI - The comparative study of diabetic specific formula and standard formula on postprandial plasma glucose control in type 2 DM patients. AB - OBJECTIVE: To compare the postprandial plasma glucose level after diabetic specific formula (DSF) and standard formula (SF) administration in type 2 diabetic patients. MATERIAL AND METHOD: Thirty type 2 diabetic patients were included in the present randomized, controlled, double-blind, cross-over study. Subjects received DSF and isocaloric SF as a bolus administration of 400 mL while continuing their anti-diabetic medications. Venous blood samples were collected and analyzed to assess plasma glucose levels at pre- and at 30, 60, 90, 120, and 180 min post-administration of the formulas. RESULTS: Postprandial glucose profiles were significantly lower with DSF compared to SF administration determined as a mean glucose concentration at 2-hour post-administration. The glucose area under the curve (AUC) after DSF consumption was 33% lower than the AUC after SF consumption, p < 0.001. CONCLUSION: Use of DSF resulted in a significantly lower postprandial rise in plasma glucose concentrations than using SF. It should be the preferred option in diabetic patients who need nutritional support. PMID- 25137876 TI - The reliability of calculated low-density lipoprotein cholesterol from four different formulas in Thai diabetic patients. AB - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is usually calculated by the Friedewald formula but it has certain limitations, especially in hypertriglyceridemia and diabetes mellitus (DM). OBJECTIVE: Assess the reliability of LDL-C levels calculated from four formulas (Friedewald, Anandaraja and colleagues, Chen et al, and Vujovic et al) when compared to direct LDL-C measurement (dLDL-C) in DM with various triglycerides (TG) levels. MATERIAL AND METHOD: The present study included 2,967 fasting Thai diabetic patients with TG levels less than 400 mg/dl. The total cholesterol and TG levels were measured by enzymatic colorimetric assay. The high-density lipoprotein cholesterol and dLDL-C levels were measured by homogeneous enzymatic colorimetric assay. The calculated LDL-C (cLDL-C) from each formula was compared to dLDL-C. In addition, the degree of agreement between the methods was assessed. RESULTS: The mean and standard deviation (SD) of dLDL-C was 122.3 (37.1) mg/dl, the mean (SD) of cLDL-C from the formula of Friedewald (F-LDL-C), Anandaraja and colleagues, Chen et al, and Vujovic et al (Vu-LDL-C) were 115.2 (35.8), 120.8 (35.2), 116.6 (34.2), and 123.9 (37.4) mg/dl, respectively. In aspect of the accuracy defined as the percentage of dLDL-C minus the cLDL-C within -10 to 10 mg/dl; the accuracy of Vu-LDL-C were higher than the other cLDL-C in overall and the most of subgroups of TG levels, except in the subgroup of TG levels < 100 mg/dl which the accuracy of F-LDL-C was the highest. The overall number of dLDL-C minus Vu-LDL-C within -10 to 10 mg/dl was 2,655 cases (89.5% with p < 0.001). The Vu-LDL-C showed a little discordance with dLDL-C at the higher levels of TG. All cLDL-C had systematic differences from dLDL-C, while only Vu-LDL-C had no proportional difference. The Vu-LDL-C yielded the lowest mean of difference between dLDL-C and cLDL-C of -1.60 with SD of 6.31 mg/dl, while F-LDL-C yielded the highest value of 7.06 with SD of 7.91 mg/dl. The Vu-LDL-C had the narrowest range of 95% limits of agreement (-13.97 to 10.77 mg/dl) and the difference neither depended on the magnitude of LDL-C measurements nor had proportional error. CONCLUSION: The modified Friedewald formula of Vujovic et al provided the most accuracy with acceptable degree of agreement in DM compared to those derived from the original Friedewald formula or the others. The interference caused by hypertriglyceridemia was obviously diminished; thus, the formula of Vujovic et al is more reliable than the others in DM if TG levels are range from under 400 mg/dl to 100 mg/dl. PMID- 25137877 TI - Experience with surgical treatment of retroperitoneal soft tissue sarcomas at a university hospital in Thailand. AB - BACKGROUND: Retroperitoneal soft tissue sarcomas (RSTS) are rare malignant tumors with a distinguishing feature of slow growth in the silent retroperitoneal space. The patients usually present late with a large retroperitoneal mass surrounded by the major vascular structures and visceral organs rendering curative resection an extremely difficult and risky operation. The purpose of the present study was to demonstrate surgical experience and results of treatment of RSTS at King Chulalongkorn Memorial Hospital. Operative techniques of these complex surgical procedures were also described. MATERIAL AND METHOD: A retrospective study was performed in patients who had RSTS and underwent surgical resection between June 2003 and November 2011 at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. All patients were followed after the operations until death or last follow-up at the out-patient clinic in October 2012. Data collection included demographic data, details of operations, operative complications, neoadjuvant and adjuvant chemoradiation therapy, local recurrence, treatment of local recurrence, and 5-year overall survival rate. Factors associated with local recurrence were also examined. RESULTS: During the 9.4-year period, 18 patients entered into the present study. Fourteen (77.8%) were female and four (22.2%) were male. The age ranged from 44 to 80 years (median 53.5 years). Duration of symptoms ranged from one week to 24 months (median 3.5 months). The tumor size ranged from 10 to 48 cm (median 27 cm) in greatest dimension. All patients underwent preoperative CT scan. Preoperative core needle biopsy was performed in one patient. One patient had preoperative radiation therapy. Sixteen patients (88.9%) underwent complete gross resection (CGR) (R0 or R1 resection) and two (11.1%) had palliative resection (R2 resection). All patients who had CGR (n = 16) had one or more contiguous organ resection (kidney 87.5%, colon 50%, or adrenal gland 43.7%). The operative time ranged from 120 to 360 minutes (median 330 minutes). The operative blood transfusion ranged from 0 to 12 units (median 2.5 units). Postoperative bleeding complication requiring reoperation occurred in three patients (16.7%). One patient had postoperative uncomplicated pancreatic fistula. There was no perioperative mortality. The final pathological reports were liposarcoma in 15 patients (83.3%). Other histology were atypical lipomatous tumor malignant fibrous histiocytoma, and unspecified spindle cell tumor in one patient each. Two patients who had palliative resection died at six and 16 months after the operations. Local recurrence occurred in five patients who had CGR (31.3%). One of them died at 60 months after the operation. The median follow-up time in patients who underwent CGR was 39.5 months (range 12-114 months). The 5-year overall survival of the entire cohort was 73.5% (95% CI: 44.3-88.4%). The 5-year overall survival of patients who had CGR was 83.3% (95% CI: 53.5-98.5%). Univariate analysis of the tumor size, tumor grading, status of the surgical margins, and primary operation or re-resection revealed no statistical significance in patients who had CGR with and without local recurrence. CONCLUSION: Acceptable outcomes after complete surgical resection of the RSTS were achieved from this small but important case-series. The authors have demonstrated that CGR with concomitant resection of the contiguous organs can be safely performed in patients with large RSTS. Preoperative CT scan was invaluable for diagnosis and treatment plan. Preoperative core needle biopsy was not necessary when preoperative CT scan was diagnostic. Intention for curative resection should be attempted whenever possible to minimize chance of local recurrence and improve survival. Experience of the surgical team is an important factor for successful results when conducting these technically demanding operations. PMID- 25137878 TI - Reliability of a Thai version of the International Prostate Symptom Score (IPSS) for the Thai population. AB - OBJECTIVE: To develop and test the reliability of a Thai version of the International Prostate Symptom Score (IPSS-Th). MATERIAL AND METHOD: A Thai version of the International Prostate Symptom Score (IPSS-Th) was developed after conducting many steps. The original English version of the International Prostate Symptom Score (IPSS) was translated into Thai by three urologists working independently. After having compared the original English version with various translations, the final Thai version was obtained. Fifty Thai males possessing a good understanding of both English and Thai were asked to complete the Thai version of the IPSS. Two weeks later, they were asked to complete the English version of the IPSS. Internal consistency was assessed using Cronbach's alpha. Next, 118 Thai males were tested using the Thai version of the IPSS and retested after two weeks. As such, the reliability of the Thai version of the IPSS was evaluated using the test-retest method. RESULTS: For the Thai IPSS version, Cronbach's alpha was 0.77 and the English version of the IPSS was 0.88. The test retest reliability was 0.96. CONCLUSION: The Thai version of the IPSS was found to be reliable and should be a useful tool for patient assessment, follow-up, and research in the population of Thai-speaking patients. PMID- 25137879 TI - A prospective analytical study of the effects and adverse events of alendronate (Aldren70) treatment in Thai postmenopausal women. AB - OBJECTIVE: To elucidate the efficacy and adverse events of alendronate (Aldren70) after 12 months of treatment in 50 to 70 years old postmenopausal women. MATERIAL AND METHOD: The authors observed 50 postmenopausal women who had clinical conditions of osteopenia or osteoporosis and had never been treated with alendronate acid. Bone mineral density (BMD) of L1-L4, the left hip, and the left forearm were performed at the initial assessment and after 12 months of treatment. The serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (PINP) and beta-crosslaps (beta-CTx) were performed at the baseline and then after 3 months, 6 months and 12 months of treatment. The data were analyzed using the SPSS software. Paired t-test was used to compare lumbar spine, hip and forearm before and after treatment. RESULTS: Treated by using Aldren70 once weekly for one year the BMD of the lumbar spine increased highly up to 11.26% (g/cm2) and 25.82% (T-score) from the base line (p < 0.001 and p < 0.001, respectively). On the other hand, the change in BMD of the left hip increased 17.54% (g/cm2), 8.2% (T-score), at the left forearm increased 3.96% (g/cm2), 7.62% (T-score) after 12 months respectively. There was significant increase of BMD between before and after 12 months. The mean values of bone markers at the 0.05 level before treatment, three months, six months, and 12 months of treatment in osteocalcin were 0.2813, 0.1242, 0.896, and 0.0889 ng/ml respectively. The PINP were 36.1762, 19.3894, 14.3084, and 15.1260 ng/ml respectively. Beta crosslaps were 0.2813, 0.1242, 0.0896, and 0.0889 ng/ml respectively. Adverse events found in five patients were the symptoms of stomachache (2.4%), constipation/diarrhea (1.2%), palpitation (1.2%), and muscle/bone pain (1.2%). CONCLUSION: The generic alendronate (Aldren 70) in our clinical trial was found to be highly effective at the spine concerning the bone mass improvement and less at the hip and wrist joints in comparison. All the result figures met the standard efficacy after 12 months follow-up by increasing bone mass and reducing serum bone markers. PMID- 25137880 TI - Acetabular cup placement in navigated and non-navigated total hip arthroplasty (THA): results of two consecutive series using a cementless short stem. AB - BACKGROUND: Acetabular component malposition has been linked to increased rates of dislocation, impingement, pelvic osteolysis, cup migration, leg length discrepancy and polyethylene wear in patients undergoing total hip arthroplasty (THA). OBJECTIVE: Compare the acetabular component positioning and the operative time in two consecutive short-stem cementless THA series without and with using an imageless navigation. MATERIAL AND METHOD: The retrospective study consisted of 31 cases of short-stem cementless THA without navigation (NNAV) and 30 cases with navigation (NAV). CT scans were performed in all cases at two-month or later postoperatively. The abduction and anteversion angles measured on postoperative CT were compared between two groups using t-test. The percentage of cup placement (abduction, anteversion and combined) within the safe zone for each group was compared using Chi-square test at a 0.05 level of significance. The operative time was compared between two groups using t-test. RESULTS: The mean abduction was 43.97 (range, 33-52, SD 4.44) in NNAV group and 41.37 (range, 37-45, SD 2.01) in NAV group. This difference was significant (p = 0.004). The mean anteversion was 22.58 (range, 2-39, SD 10.68) in NNAV group and 13.57 (range, 7-18, SD 3.28) in NAV group. This difference was significant (p < 0.001). According to the criteria of Lewinnek et al, 96.8% in NNAV group were placed within the safe zone for abduction, 51.6% for anteversion, and 48.4% for both abduction and anteversion. In NAV group, all 30 cups (100%) were placed within the safe zone for abduction, anteversion, and both. There were significant differences in the percentage of cup placement within the safe zone for anteversion (p < 0.001), for both abduction and anteversion (p < 0.001) but not significant for abduction (p = 0.32) between two groups. The mean operative time was 107.09 and 110.67 minutes for NNAV and NAV group respectively, this difference was not significant (p = 0.49). CONCLUSION: The present study demonstrated a significant increase in the placement of acetabular cups within the safe zone using imageless navigation compared to freehand technique, especially at anteversion angle. PMID- 25137881 TI - Prevalence of atypical femoral fractures in Thai patients at a single institution. AB - OBJECTIVE: Evaluate the prevalence of atypical femoral fracture (AFF) in Thai patients at a single institution based on the 2010 and 2013 American Society of Bone and Mineral Research (ASBMR) criteria and the sensitivity and specificity of each radiographic feature of AFF to identify bisphosphonate treatment. MATERIAL AND METHOD: The authors retrospectively reviewed plain radiographs of 856 patients who were diagnosed with subtrochanteric or femoral shaft fractures between 2002 and 2013. Only those who had major radiographic features of AFF according to the 2010 ASBMR criteria were included. Next, the prevalence of atypical fracture was recalculated based on the revised 2013 ASBMR criteria. Furthermore, the specificity and sensitivity of each radiological finding to detect bisphosphonate treatment were calculated. RESULTS: The prevalence of atypical femoral fracture based on 2010 ASBMR criteria at this institution was 5.7%. Two patients had all radiographic features of AFF but sustained a high energy trauma and could be diagnosed with AFF based on the 2013 ASBMR criteria. Among all of the radiographic features to define AFF, a localized periosteal thickening of the lateral femoral cortex was the most specific sign to detect bisphosphonate treatment (0.98; 95% CI 0.96-0.99). CONCLUSION: The prevalence of AFF in Thai patients at a single institution was approximately 6%. Although the prevalence of AFF did not dramatically change after applying the 2013 revised ASBMR criteria, this reflected some gap in the diagnosis criteria, which should require further refinement. The authors suggested that the ASBMR criteria should be used only with those having acute fractures. PMID- 25137882 TI - Diagnostic properties of the STOP-Bang and its modified version in screening for obstructive sleep apnea in Thai patients. AB - OBJECTIVE: To test the diagnostic properties of the original and a modified STOP Bang, as well as testing the additional use of a waist-to-height ratio (WHtR) of > or = 0.55 in screening for obstructive sleep apnea (OSA) in Thai patients. MATERIAL AND METHOD: Three hundred and three patients (186 males and 117 females) who underwent anthropometric measurement and standard polysomnography were asked to complete the STOP-Bang questionnaire. Subjects were considered high-risk if their scores were > or = 3. Patients with significant co-morbidities were excluded. RESULTS: Screening for OSA involved measurements of STOP-Bang sensitivity, specificity, positive predictive value, and negative predictive value at several apnea-hypopnea index (AHI) cut-off points. At AHI 5, these values were 87.3%, 48.1%, 82.2%, and 52.2%, respectively. At AHI 15, these values were 92.6%, 36.4%, 58.5%, and 83.6%, respectively. The modified STOP-Bang (using a cut-off of BMI > 30 kg/m2) showed slightly increased sensitivities at the AHI cut-off points of 5 and 15 with values of 88.7% and 93.2%, respectively, with improved area under the curves. Furthermore, by applying the WHtR of > or = 0.55 to those patients who were classified as high-risk by the questionnaires, the specificities for predicting OSA were improved to 85.2% and 76.1% for the aforementioned cut-off points, respectively. CONCLUSION: Both STOP-Bang and its modified version were highly sensitive measures for OSA screening in medical or dental clinics. However, the modified version might be more suitable for Thais and Asians, and the additional use of WHtR > or = 0.55 might be useful for reducing the unnecessary sleep investigation or management in those who were classified as high-risk patients. PMID- 25137883 TI - Clinical outcome of postoperative radiotherapy with or without chemotherapy in adult glioblastoma multiforme in Ramathibodi Hospital: a retrospective study. AB - OBJECTIVE: To identify the treatment outcome of glioblastoma multiforme (GBM) in Ramathibodi Hospital from overall survival rate and related prognostic factors. MATERIAL AND METHOD: Medical records of patients with histological diagnosis of GBM treated at Radiation Oncology Division, Radiology Department, Ramathibodi Hospital between 2000 and 2010 were reviewed and available data extracted for evaluation of treatment outcome. RESULTS: There were 47 patients with mean age at diagnosis of 51.9 years (range from 18 to 82 years). Surgery (partial 76.6%, total 12.8%, and biopsy 10.6%) followed by postoperative radiotherapy (mean dose 52 gray) was the treatment of choice with or without concurrent and adjuvant Temozolomide (TMZ). With median follow-up time of 0.9 years, the median survival of the patients was 2.1 years (95% CI 1.08-7.36), whereas one and two-year overall survival rates were 78.0% and 57.8%, respectively. In univariate analysis, persistent neurological deficit after surgery and presenting symptom of visual disturbance were identified to lower overall survival while multivariate analysis, younger age, and higher radiation dose were identified as favorable prognostic factors to improve overall survival. Re-surgery or re-irradiation in some selected cases of recurrent or progressive disease was considered as a choice for palliative treatment. CONCLUSION: Proper management of GBM patient was surgical removal and postoperative radiotherapy with or without chemotherapy. Proper palliative treatment modality was considered in selected cases of recurrent or progressive disease. PMID- 25137884 TI - Committed suicide: forensic autopsy analysis at Ramathibodi Hospital during year 2001-2010. AB - BACKGROUND: Suicide is one of the most important causes of death in the world. To study the behaviors and risk factors may be helpful to prevent suicide. OBJECTIVE: To retrospectively study the factors that affected suicide in forensic postmortem cases at Ramathibodi Hospital, Bangkok, Thailand between 2001 and 2010. MATERIAL AND METHOD: Two hundred ninety suicidal cases from 7,102 forensic postmortem autopsies in Ramathibodi Hospital between 2001 and 2010 were descriptively retrospective studied. Study topics included sex, age, nationality, year, methods of suicide, and HIV. RESULTS: The suicide-rate in the present study varied between 2.53% and 6.91% (average 4.08%) of the forensic autopsy cases. The peak was found in 2003. Males had higher suicide rate than females [ratio of M:F of 4.3:1 (235 males and 55 females)]. The age varied from seven years to 91 years. Although the average age of suicide was 37.38 years, the peak was found in the young adult (age group of 21 to 30 years). Male, younger age, and foreigner were related to suicide with statistical significance. Hanging was the most frequent method of suicide followed by fall from height (62.1% and 17.2% respectively) and by firearm (in male) and toxic substance ingestion (in females). Of all the suicide, 5.1% were HIV seropositive, which is slightly more than non-HIV cases (4.0%) but this was not statistically significant. CONCLUSION: The suicidal cases among unusual death were related to varieties of factors. Male, younger age, and foreigner were significant related to suicide. Hanging and falling from height were the most frequent method of suicide. PMID- 25137885 TI - Necrotizing fasciitis: a rare manifestation of late-onset neonatal group B streptococcal infection. AB - Preterm infants have a risk factor of developing late-onset group B streptococcal (GBS) infection. A 62-day-old infant who was a former 25-week male infant presented with fever and an erythematous, warm and tender, soft tissue swelling in the right submandibular region. He was diagnosed with cellulitis. Within 72 hours, his lesion had rapidly progressed to necrotizing fasciitis. His blood culture grew penicillin-sensitive GBS. This reported case illustrates necrotizing fasciitis as a rare manifestation of late-onset neonatal GBS infection. PMID- 25137887 TI - President's update. Leading the way in primary health care. PMID- 25137886 TI - Paget's disease of bone in ethnic Thai presented with urologic symptoms and misleading as metastatic prostate cancer: report of a case with a review of the literature. AB - Paget's disease of bone is common in some parts of Europe and in countries inhabited by European emigrants. In Western Countries, Paget's bone disease is one of the priorities in differential diagnosis for elderly patients who present osteoblastic lesions, so it is unlikely to be overlooked, even though patients may present symptoms unrelated to bone lesions. However in Asian countries where Paget's disease is rare, metastatic prostate cancer appears to be the most common cause for osteoblastic lesions, thus, the Paget's disease is unlikely to be of much concern. This may lead to undue emphasis on investigations to support the diagnosis of prostate cancer. In this report, a 69 year-old man presented pain in the right leg and difficulty urinating. The plain film showed osteoblastic lesions of the right pelvic bone and lumbar spine. The pertinent routine laboratory findings revealed increased levels of serum alkaline phosphatase 125 U/L (normal 27-86). Metastatic prostate cancer was highly suspected and investigations focused upon this, including a serum prostate specific antigen assay, a transurethral cystoscopic examination, an intravenous pyelogram, and an ultrasonogram of the prostate gland. However all of these investigations failed to support prostate cancer. Bone biopsy was performed twice, resulting in a report supporting Paget's disease of bone. The patient was treated with alendronate for three months. Radiologic findings, six months later, showed signs of improvement. He died one year later of heart failure that could plausibly had been a cardiovascular complication of Paget's disease. Better awareness of Paget's disease in Thailand and other Asian countries should reduce the incidence of unnecessary investigations and avoid a misleading diagnosis, which could lead to inappropriate treatment for metastatic prostatic cancer and undesirable psychological impact associated with being misinformed regarding malignancy. PMID- 25137888 TI - Clarification on breastfeeding article from previous issue. PMID- 25137889 TI - Response from author. PMID- 25137890 TI - Nursing's purpose. PMID- 25137891 TI - Can decreasing antipsychotic use lead to growth in mental and emotional health? PMID- 25137892 TI - Assignment of Client Care Guidelines enhanced to focus on leadership of RN role. PMID- 25137893 TI - An interview with Deputy Minister Janet Davidson. PMID- 25137894 TI - Every nurse a leader. PMID- 25137895 TI - Radiology. In search of a clear picture. PMID- 25137896 TI - On centralisation versus localisation. Stop one-track thinking to boost public support. PMID- 25137897 TI - Our safe staffing guidance is based on strong evidence. PMID- 25137899 TI - A Tory manifesto should not be conservative. How the NHS divides the Tories. PMID- 25137898 TI - Put the constitution on the front line. PMID- 25137900 TI - Imaging. Putting PET CT to the test. PMID- 25137901 TI - Patients experience. Give patients a valid voice to broadcast. PMID- 25137902 TI - Acute care. A&E needs more than a sticking plaster solution. PMID- 25137903 TI - Commissioning. Come together to put cancer care on the right path. PMID- 25137904 TI - Unraveling the mystery of MU audits. 7 strategies to protect your practice. PMID- 25137905 TI - Managing transitions of care. Effective care transition management is a key to achieving value-based care for your patients. PMID- 25137906 TI - 4 ways to protect your practice's schedule against emergencies. PMID- 25137907 TI - Post-implementation: making the EHR system work for you. PMID- 25137908 TI - Only credentialed medical assistants can enter EHR orders. PMID- 25137909 TI - Handling high-deductible patients requires communication, policies. PMID- 25137910 TI - Protect your assets by incorporating your practice. PMID- 25137911 TI - Preventing and treating COPD. PMID- 25137912 TI - How important are young adults to the ACA's insurance exchanges? PMID- 25137913 TI - Comparative analysis of early distance visual acuity in patients after coaxial phacoemulsification through the micro-incision (1.8 mm) and after standard phacoemulsification through the small incision (2.75 mm). AB - INTRODUCTION: The purpose of the study was to evaluate early postoperative visual acuity outcomes of coaxial phacoemulsification with a foldable intraocular lens implantation, performed through a 1.8 mm wide clear corneal microincision (C MICS) and to compare it with standard phacoemulsification through a 2.75 mm incision. MATERIAL AND METHODS: The examined group consisted of a non-randomised, prospective series of 130 eyes of 130 patients who underwent coaxial 1.8 mm microincision cataract surgery with foldable intraocular lens implantation (MI60, Bausch & Lomb). The reference group comprised 123 eyes of 123 patients who underwent standard phacoemulsification through the 2.75 mm incision with foldable intraocular lens implantation (Akreos Adapt AO, Bausch & Lomb). The following parameters were evaluated preoperatively and one day after the surgery: distance uncorrected visual acuity, distance best corrected visual acuity, intraocular pressure, anterior and posterior segment of the eye. All patients were divided into groups according to the LOCS III scale. RESULTS: The improvement of distance uncorrected visual acuity and distance best corrected visual acuity was observed postoperatively in both groups. The mean uncorrected visual acuity in the examined group was significantly better than in the reference group on the first postoperative day (0.88 +/- 0.18 vs 0.79 +/- 0.26). CONCLUSIONS: The early postoperative visual acuity results of C-MICS were better than the results of standard small incision phacoemulsification. As far as fast visual rehabilitation after MICS is concerned, the early uncorrected visual acuity should be considered as an important yardstick in measuring success in cataract surgery. These results are due to the MICS technique, which seems to be the minimally invasive surgery, and should be regarded nowadays as a procedure of choice. PMID- 25137914 TI - In vivo imaging of the mouse retina using high-resolution optical coherence tomography. AB - PURPOSE: In this study, we demonstrate the advantages of high-resolution optical coherence tomography for the non-invasive, in vivo, three-dimensional imaging of the mouse retina. METHODS: High-resolution optical coherence tomography images of the mouse retina were acquired using the Bioptigen Envisu R2200-HR SD-OCT system. We measured the retinal thickness and compared the measurements to those obtained using conventional histology techniques. RESULTS: High-resolution spectral-domain optical coherence tomography enables high-quality in vivo visualization of retinal structures in mice, providing an accurate quantitative description of retinal layers. Additionally, the ultra-high-speed system offers many advantages over histology, e.g., it permits the visualization of retinal microvasculature and pulsatile flow dynamics. CONCLUSIONS: Spectral domain optical coherence tomography is a new important tool for the in vivo analysis of mouse eyes. PMID- 25137915 TI - [Increased expression of endothelin-1-- a novel diagnostic marker for early AMD detection?]. AB - AIM: The relationship between ischemic vascular disease and age-related macular degeneration may indicate the role of vascular injury as the primary insult causing functional deficits in age-related macular degeneration. The vasoactive factors produced by endothelial cells include endothelin-1 (ET-1), which is one of the most potent vasoconstricting peptides. In this study we sought to explore the potential role of endothelial dysfunction in the pathogenesis of age-related macular degeneration by measuring the concentration of ET-1 in peripheral blood of individuals diagnosed with age-related macular degeneration and evaluating its intracellular expression in peripheral blood cells, on mRNA level. MATERIAL AND METHODS: Peripheral blood samples from 31 patients with diagnosed dry age-related macular degeneration and 46 patients with neovascular age-related macular degeneration were collected. Forty six age- and sex-matched volunteers without age-related macular degeneration were enrolled as a control group. ET-1 plasma levels were analyzed by ELISA and intracellular expression of ET-1 in peripheral blood cells was studied by using qRT-PCR. RESULTS: The expression of intracellular ET-1 was significantly elevated in peripheral blood cells of both dry and wet age-related macular degeneration patients compared with the control subjects. Immunofluorescence staining revealed that ET-1 was specifically expressed in the circulating endothelial cells. CONCLUSIONS: We assume that damaged endothelial cells may release a variety of vasoconstricting molecules, including ET-1, leading to derangement between the endothelium-derived relaxing and contracting factors. Local retinal ischemia consequently develops which may promote the development of retinal degeneration in patients with age-related macular degeneration, PMID- 25137916 TI - Bilateral serous retinal detachment in preeclampsia--a case report. AB - Preeclampsia is a leading cause of maternal and fetal/neonatal mortality worldwide. Serous retinal detachment is an unusual cause of visual loss in pregnancy. This is a case report of a 17-year-old patient who was admitted to the obstetric ward with symptoms of preeclampsia. The pregnancy was terminated by cesarean section at 38 gestational weeks. The patient complained of blurred vision in both eyes throughout the perinatal period. The ophthalmic examination revealed serous retinal detachment in both eyes. The optical coherence tomography demonstrated the hyporeflective area between the retinal pigment epithelium and the neurosensory retina. With blood pressure control at postpartum, there serous retinal detachment resolved spontaneously and patient's vision improved. PMID- 25137917 TI - Multifocal syphilitic chorioretinitis--a case report. AB - The aim of the paper is to report a case of a 22-year-old male patient with chronic bilateral uveitis and retinitis secondary to syphilis. Until the diagnosis, the patient had been treated symptomatically with ceftriaxone which resulted in visual acuity improvement. The patient was referred to the Sexually Transmitted Disease Clinic for causal treatment after which he did not continue further ophthalmic monitoring. After a year he contacted the Department again due to vision deterioration and a relapse of retinitis and choroiditis was diagnosed. The patient was referred to the Sexually Transmitted Disease Clinic for causal treatment which he never received as he did not present there. Since the beginning of the 21st century the incidence of syphilis has significantly increased. Although it is an infectious disease with potentially permanently debilitating effect e.g. on vision, its treatment is not compulsory in Poland. Infectious etiology and primary syphilis should always be considered in patients with progressive retinitis, choroiditis and vitritis. PMID- 25137918 TI - [Photodynamic therapy in a patient with chronic central serous chorioretinopathy- a case report]. AB - PURPOSE: The aim of the study was to evaluate the efficacy of photodynamic therapy as the treatment of chronic central serous chorioretinopathy. MATERIAL AND METHODS: A 59-year-old man was referred to the Department of Ophthalmology and Ocular Oncology, Jagiellonian University in Cracow with a complaint of recurrent visual acuity impairment in his left eye, which he had noticed for the first time three years earlier. The complete ophthalmic examination was extended by the additional diagnostic procedures of optical coherence tomography and fluorescein angiography and the patient was diagnosed with chronic central serous chorioretinopathy. He was eligible for the photodynamic therapy with a full dose of verteporfin, which was performed. The patient was subsequently re-assessed at 3 and 6 months following treatment completion. During the follow up assessment the amount of subretinal fluid on fundus examination and the best-corrected visual acuity (Snellen) were evaluated. The follow up optical coherence tomography was also performed. RESULTS: Six months after photodynamic therapy the subretinal fluid resolved completely, the distance best-corrected visual acuity improved from 0.2 to 0.5 and the near best-corrected visual acuity from 2.25 to 0.5. No treatment-induced adverse effects were observed. CONCLUSION: The photodynamic therapy may be effective in the management of selected cases with chronic central serous chorioretinopathy. central serous chorioretinopathy, photodynamic therapy. PMID- 25137919 TI - [Leukoaraiosis as a cause of non-arteritic anterior ischemic optic neuropathy--a case report]. AB - The paper presents the case of a 61-year-old man with specific symptoms of non arteritic anterior ischemic optic neuropathy. The head computed tomographyscans revealed multiple leukoaraiotic lesions. Leukoaraiosis is a disease affecting small cerebral vessels. Its pathogenesis is associated with a chronic inflammatory process and ischemic vascular endothelial dysfunction which reduce the cerebral blood flow. It cannot be ruled out that this process, alongside with Horton disease, hypertension, diabetes and atherosclerosis, may also be involved in the pathogenesis of non-arteritic anterior ischemic optic neuropathy. leukoaraiosis, non-arteritic anterior ischemic optic neuropathy. PMID- 25137920 TI - [Idiopathic choroidal neovascularization--case report]. AB - PURPOSE: To report a patient with peripapillary idiopathic choroidal neovascularization treated with an anti-VEGF (anti- vascular endothelial growth factor) agent (bevacizumab) observed during for 9 months. PATIENT AND METHODS: Twenty nine years old man was referred to the Department for diagnosis and treatment because of unilateral visual acuity decrease in the right eye (VA RE- 0.1) and metamorphopsias. The routine ophthalmic examination revealed macular edema and peripapillaryedema with epiretinal and intraretinal hemorrhages. The optical coherence tomography, fluorescein angiography, as well as laboratory tests were performed in order to exclude uveitis. Due to the difficulties in the diagnosis indocyanine green angiography was also performed. Based on clinical symptoms and the findings of the additional diagnostic procedures, the patient was diagnosed with idiopathic choroidal neovascularization. The patient was qualified for anti-VEGF therapy and received three intravitreal injections of bevacizumab at the dose of 1.25 mg, at monthly intervals. RESULTS: Significant improvement of visual acuity (VA RE - 1.0) and regression of the peripapillary edema with hemorrhages were achieved after the third injection of 1.25 mg bevacizumab. At 6 months, peripapillary scarring was observed in the area involved by the primary lesions. CONCLUSIONS: Anti-VEGF therapy is the effective treatment of idiopathic choroidal neovascularization in the described case. The visual acuity improvement and rapid regression of posterior segment lesions after bevacizumab administration were observed. PMID- 25137921 TI - [Glaucoma after laser diode treatment in retinopathy of prematurity--case series]. AB - The aim of this study was to analyze treatment and outcomes in children with glaucoma secondary to diode laser photocoagulation in retinopathy of prematurity. METHODS: The group of 1507 newborns, examined as outpatients between 2008 and 2013, were retrospectively analyzed. Five patients (0.3%) (nine eyes) with glaucoma following laser treatment for retinopathy of prematurity were identified. Demographic and clinical data was obtained from medical records and compared with corresponding results in the group of glaucoma-free children subjected to diode laser photocoagulation for retinopathy of prematurity. The statistical analysis included Shapiro-Wilk test and U-Mann-Whitney test with statistical significance level p < 0.05. RESULTS: The following data was collected - mean post-menstrual age at the moment of photocoagulationwas 42 Hbd (38-42) and it was 49.9 (43-54) weeks at the moment of diagnosis of angle-closure glaucoma. The intraocular pressure was significantly elevated in nine in ten eyes which was confirmed objectively and the mean intraocular pressure was 32.0 mmHg (21.6-42.4). The mean corneal diameter was 11.25 mm (10-13) and it was associated with the decreased corneal thickness in pachymetry (p < 0.05). Six eyes (66.6%) required surgical intervention and intraocular pressure normalization was achieved in all patients. Additionally, the affected eyes tended to be myopic (mean spherical equivalent -1.625 diopter) and have a greater axial length (p < 0.05). CONCLUSIONS: Secondary glaucoma can develop following laser treatment for severe retinopathy of prematurity. Topical treatment and surgical intervention provide effective management. PMID- 25137922 TI - [A case of familial pupillary iris pigment epithelium cysts]. AB - Iris cysts are rare lesions. In some cases, they may mimic melanoma and cause diagnostic difficulties. Through imaging tests such as ultrasound biomicroscopy we can evaluate the structure changes and determine the location for easy diagnosis. Iris cysts often require only observation. In some cases specialist treatment is necessary. One of the methods is transpupillary cystotomy perform using the Nd:YAG laser. The paper presents the case of familial pupillary cysts of the iris pigment epithelium in a father and a daughter. PMID- 25137923 TI - Is binocular vision worth considering in people with low vision? AB - In someone with good vision, binocular vision provides benefits which could not be obtained by monocular viewing only. People with visual impairment often have abnormal binocularity. However, they often use both eyes simultaneously in their everyday activities. Much remains to be known about binocular vision in people with visual impairment. As the binocular status of people with low vision strongly influences their treatment and rehabilitation, it should be evaluated and considered before diagnosis and further recommendations. PMID- 25137924 TI - [Not only optic neuropathy: new molecular and clinical aspects of OPA1 gene mutations]. AB - Autosomal dominant optic nerve atrophy is the most frequent dominantly inherited optic neuropathy. The main causesof the disease are OPA1 gene mutations, which are detected in about 60% of patients. Encoded by the nuclear genome the OPA1 protein plays an important role in a wide variety of processes crucial to the proper functioning of mitochondria, the role of OPAl in many of them has been discovered recently. A detailed study of patients with mutations in the OPA1 gene has shown that about 20% of them present symptoms of a multiple system disease, which may include hearing loss, progressive external ophthalmoplegia, ataxia, myopathy, peripheral neuropathy, spastic paraparesis and multiple sclerosis-like illness. This clinical manifestation is difficult to differentiate from other neurodegenerative diseases, that is why genetic testing is very important in order to determine the molecular basis of the disease in these patients. PMID- 25137925 TI - [Terson syndrome--a literature review]. AB - Tersone syndrome was first described in 1900 as haemorrhages in the eye that occur as a consequence of intracranial hemorrhage. The main cause of the syndrome in adults is a subarachnoid hemorrhage following the rupture of intracranial aneurysm. The pathogenesis has not been fully understood. It is believed that the increase of intracranial pressure results in the hemodynamic changes in ocular vessels. Reported symptoms include decrease of visual acuity following generalized symptoms such as headache, loss of consciousness and meningealsigns. Physical examination usually reveals vitreous hemorrhage (classic Terson's syndrome) and other forms of intraocular hemorrhage. The authors reviewed the available literature on the Terson's Syndrome. Clinical presentation, pathogenesis, diagnosis, and available treatment options are presented and discussed, considering the rare occurrence of this disease. PMID- 25137926 TI - [Congenital optic disc anomalies--own observations]. AB - The aim of this article is to present a clinical picture of congenital optic nerve anomalies, which occur quite frequently in the general population, may cause low vision and visual field defects. These abnormalities can coexist with central nervous system defects or the other ocular abnormalities. Some of them may be misdiagnosed as papilloedema during the episode of intracranial fluid pressure elevation or glaucomatous neuropathy. Diagnosing the congenital nerve optic disc defects coexisting with multiorgans anomalies requires multidisciplinary medical care especially in babies. developmental optic disc anomalies, congenital eye abnormalities, differential diagnosis. PMID- 25137927 TI - [Lucian Rydel (1833-1895)--ophthalmologist and the rector of the Jagiellonian University of Cracow]. AB - Lucjan Rydel (1833-1895), was a Polish ophthalmologist, professor and the head of the Department of Ophthalmology in Cracow, Dean of the Faculty of Medicine (1875 1878 and 1882-1883), the rector of the Jagiellonian University (1884-1888). He studied medicine at the Jagiellonian University and the University of Vienna, where he received the title of Doctor of Medicine in 1859, and Doctor of Surgery in 1861. He was an assistant of F. Arlt. He had four sons: Adam (neurologist), Lucjan (poet), Mieczyslaw, Stanislaw, and two daughters: Helena and Anna. His son Lucjan (1870-1918) was a poet and a playwright of the Young Poland movement, a journalist, a critic, a social activist and a pedagogue. He was a friend of Stanistlaw Wyspianski. Lucjan Rydel was an author of dozens of clinical and research works published in Polish and German. In his works, he described the diagnosis and treatment of cataracts, corneal diseases, retinal degeneration, retinal detachment and myopia. His article published in 1864 was one of the first comprehensive works in Polish literature devoted to retinitis pigmentosa. PMID- 25137928 TI - "Employers must back speaking out safely drive". PMID- 25137929 TI - NICE sets out stall on staffing. PMID- 25137930 TI - Lack of nurses at the top leads NMC to set up advisory panel. PMID- 25137931 TI - Nurses "more cautious" than doctors in prescribing. PMID- 25137933 TI - NICE: SIDS linked to sleeping with baby. PMID- 25137932 TI - Training scheme cuts dementia drug use. PMID- 25137934 TI - Preterm survival better in larger units. PMID- 25137935 TI - Resist demands for antibiotics, staff told. PMID- 25137936 TI - Nurses support prostate cancer drug appeal. PMID- 25137937 TI - Nurses in Wales to get pound 160 but ministers reject blanket 1% pay rise. PMID- 25137938 TI - End-of-life nursing care getting better. PMID- 25137939 TI - Duty of candour for NHS closer to becoming law. PMID- 25137940 TI - RCN ends indemnity insurance cover for employed members. PMID- 25137941 TI - WW1 nurse to be celebrated with Royal Mint coin. PMID- 25137942 TI - "Unison says yes to strike action and knows it can be done safely". PMID- 25137943 TI - "Helping care home residents is not always in their interests". PMID- 25137944 TI - Sobering thoughts about liver disease. PMID- 25137946 TI - Overweight and obese adults: lifestyle weight management. PMID- 25137945 TI - Comparing nurses' and doctors' prescribing habits. AB - BACKGROUND: Nurses' prescribing activity in a mental health trust prompted examination of whether nurse prescribers replicate their mentors' prescribing habits. AIM: To explore nurses' and medical mentors' prescribing habits to inform nurse-prescribing strategy. METHOD: The trust's 14 most-active nurse prescribers and nine of their medical mentors were interviewed. Transcripts underwent phenomenological analysis. RESULTS: 64 themes emerged showing nurses and doctors approach prescribing differently. Themes were grouped into four categories. DISCUSSION: Nurse prescribers tend to have greater holistic awareness of patients but are also more risk averse. CONCLUSION: Greater strategic vision is required to incentivise nurse prescribing; on its current trajectory it will not meet identified prescribing needs. PMID- 25137947 TI - Nursing care for end-stage liver disease. AB - Nurses are seeing more and more patients with liver disease, many of whom are under 65. Most common causes are avoidable and, as liver disease may take up to 30 years to develop, identifying those at risk is key. Patients with liver disease often have a fluctuating course of complications that needs a team approach to care. Improving end-of-life care can also reduce the number of these patients who die in hospital. This article, the first in a two-part series, explores some common complications of liver disease and best practice for nurses treating patients with end-stage liver disease. PMID- 25137948 TI - A toolkit for encouraging activities in care homes. AB - Activity is vital for the physical and psychological wellbeing of care home residents. It should be an integral part of their daily routine but can be viewed as an additional burden for busy staff. Activity is defined as everything we "do", and even older people who are frail can still be active. Nurses need to consider how activity can be incorporated into residents' daily lives; the Living Well Through Activity in Care Homes toolkit, produced by the College of Occupational Therapists, aims to help staff provide meaningful activities for residents. PMID- 25137949 TI - Reducing need to restrain vulnerable patients. AB - A multiprofessional consortium led by the Royal College of Nursing has developed guidance on reducing the need for restrictive interventions in hospitals and residential or care homes. The guidance, published by the Department of Health this year, states that nurses and other staff must create therapeutic environments that promote wellness, and must use restrictive interventions only when there is a real possibility of harm to the person, staff or the public. Staff must not restrain people in a way that affects their airway, breathing or circulation, and restrictive intervention must not include the deliberate application of pain. Interventions used must always be the least restrictive option to meet the immediate need. PMID- 25137950 TI - 60 seconds with Garry Swann. PMID- 25137951 TI - Driving down cases of TB. PMID- 25137952 TI - [Healthy aging]. PMID- 25137953 TI - [Genevieve Ruault, homage to a grand lady]. PMID- 25137954 TI - [Cerebrovascular accidents, don't forget number 15]. PMID- 25137955 TI - [The benefits of home health aides]. PMID- 25137956 TI - [Decision making, medical treatment and the end of life]. PMID- 25137957 TI - [Preventing psychological suffering and suicide in the elderly]. PMID- 25137958 TI - [A simple tool to measure the immediate wellbeing of elderly people in nursing homes]. AB - Immediate wellbeing and quality of life in an institution are of paramount importance. The assessment of the quality of life of elderly people is both complex and poorly adapted to daily practices. The instant assessment of wellbeing tool (EVIBE), developed in the field, is an original and practical alternative. This tool allows caregivers to carry out an immediate assessment and a qualitative approach with residents while involving professionals in a well treatment approach improving daily practices. PMID- 25137959 TI - [Speech therapy for cognitive disorders in elderly patients]. AB - The aim of providing speech therapy to elderly patients, in the framework of a personalised approach, is to help them maintain their autonomy and delay their move to a specialised hospital. The family and caregivers play an essential role in ensuring the success of this therapy. PMID- 25137960 TI - [Interprofessionalism in geriatrics]. AB - A system for the coordinated care of elderly people in geriatrics was set up at Luxembourg general hospital. The creation of the short-stay geriatric unit resulted in a reorganisation which questioned the notions of team, cohesion and skill. This article describes the successful experience and the benefit it has brought patients. PMID- 25137961 TI - [Non pharmacological management of cognition disorders. Listening and calming tensions]. PMID- 25137962 TI - [Non pharmacological therapies for Alzheimer's]. AB - A number of non pharmacological therapies for Alzheimer's disease exist, focusing on cognitive, psycho-social, sensory, physical and environmental aspects. Although their absolute efficacy has not been proven, their results are encouraging. Outpatient therapy to maintain patients' competencies changes how the objectives and methods of patient care are viewed. By establishing individualised, relational care, it aims above all to preserve the patient's quality of life. It recognises the role, contribution and skill of the caregiver. PMID- 25137964 TI - [Nursing care and essential oils in geriatrics]. AB - Aromatherapy is a valuable complementary therapeutic tool which is increasingly being used in hospitals. Essential oils help to improve patients' quality of life. They can be used for well-being purposes as well in specific nursing procedures. Some services offer aromatherapy through diffusion, inhalation, massages or aromatic baths. The benefits for healthcare teams as well as for patients are undeniable. There is also a significant reduction in the consumption of certain drugs. PMID- 25137963 TI - [The snoezelen as a form of caring]. AB - The concept of the snoezelen originated in The Netherlands. It is based on the stimulation of the senses and relaxation. It offers a unique opportunity for human contact between the caregiver and the patient, which helps to restore self awareness and improve the distorted body percept. It emphasises the caring aspect of nursing. PMID- 25137965 TI - [Haptonomy in geriatric units]. AB - Haptonomy lies at the heart of the human relationship. This specific contact concerns the most sensitive part of the human being and considers the person as a whole. The indications are notably the feeling of abandonment or insecurity. Testimony. PMID- 25137966 TI - [The therapeutic meal, a moment of sharing]. AB - Therapeutic meals were set up at Chateau-Gombert geriatric clinic in Marseille on the initiative of the hospital's dietician and psychologist. They are an opportunity for elderly people who may or may not have cognitive disorders and who are suffering from eating disorders to enjoy and share in a convivial moment and to rediscover a sometimes forgotten ritual. The initiative has had a positive effect on the quantity of food eaten. PMID- 25137968 TI - [A storyteller in gerontology]. AB - Storytelling in geriatrics is a way of contributing to the construction of an alternative to the pharmacological treatment of cognitive disorders. To carry out such an activity, aside from having a repertoire of targeted stories and the talent of a good storyteller, it is important to know how to create a convivial atmosphere where the patient will feel appreciated and valued. PMID- 25137967 TI - [A garden as a care tool in a cognitive-behavior unit]. AB - Cognitive-behaviour units are specialised units within follow-up and rehabilitation care services for people suffering from Alzheimer's disease. These units were created in response to measure 17 of the 3rd Alzheimer's Plan. To stabilise behavioural disorders, as part of a non pharmacological care plan, the therapeutic garden is a useful care tool. This article presents an original initiative in Nancy. PMID- 25137969 TI - [Bibliography. Non pharmacological management of cognition disorders]. PMID- 25137970 TI - [Never neglect the medical history of a patient]. PMID- 25137971 TI - [Prevention of inappropriate prescriptions in the elderly]. PMID- 25137972 TI - Safe and sound. Informed design approaches help to prevent patient harm. PMID- 25137973 TI - A new utility. PMID- 25137974 TI - Data-driven planning. Statistical research an Lean concepts help determine space needs. PMID- 25137975 TI - Measuring up. Strategies for benchmarking cooling water systems. PMID- 25137976 TI - Built to last. Furniture designers push the envelope on durability, comfort and ergonomics. PMID- 25137977 TI - Surface safety. Best practices in surface and medical device disinfection. PMID- 25137978 TI - Adapting to the new health care environment. PMID- 25137979 TI - Applying Lean principles to ES operations. PMID- 25137980 TI - A deciding role. ES involvement in the design and construction process. PMID- 25137981 TI - ["I am mostly interested in special, seemingly unsolvable problems related to surgery" Conversation with Dr. Gabor Vogt]. PMID- 25137982 TI - [Once more on the heart cathedral--paradogmas for the heart as a symbol]. PMID- 25137983 TI - [The artist and his age]. PMID- 25137984 TI - [The Helsinki Declaration at 50 years: comments on the 2013 modifications]. PMID- 25137985 TI - [A professor of ophthalmology at the University of Harkov]. PMID- 25137986 TI - Cross-border collaboration. PMID- 25137987 TI - Cure for the common clinic. PMID- 25137988 TI - A standard of care: patient-safety advocates issue call for watchdog. PMID- 25137989 TI - HHS defends expanded 340B drug discounts. PMID- 25137990 TI - States struggle to find sources to fund Obamacare exchanges for 2015. PMID- 25137991 TI - Diagnosing a community's health needs. Not-for-profit hospitals target health improvement efforts under reform law. PMID- 25137992 TI - The flaw in the law. Millions at risk of losing coverage in lawsuit challenging subsidies. PMID- 25137993 TI - Better reporting--the next step in reducing patient harm. PMID- 25137994 TI - Healthcare leaders must live in today's world and plan for tomorrow's. PMID- 25137995 TI - Committed to publicly reporting both the good and the bad. PMID- 25137996 TI - Hospital margins slump due to squeeze from volume, rates, investments. PMID- 25137997 TI - Smarter checklists. Designers of comprehensive app hope to advance hospital use of patient-safety tools. PMID- 25137998 TI - The big bulk up. Hospital systems grow through dealmaking as regulators fret about prices. PMID- 25137999 TI - Efficient, quality care can aid shrinking margins. PMID- 25138000 TI - Acquisitions and affiliations: how the new wave is different. PMID- 25138001 TI - Maine hospital slashes transfusions, reducing patient risk, costs. PMID- 25138002 TI - Think more about how technology affects quality. PMID- 25138003 TI - Don't blame fat. PMID- 25138004 TI - The changing lives of teens. Kids have cut some risky behaviors--and picked up others. PMID- 25138005 TI - Dieters, beware. Supplements for weight loss are heavy on claims and light on scientific proof. PMID- 25138006 TI - The contraception showdown. PMID- 25138007 TI - Applications of induced pluripotent stem cells in the modeling of human inflammatory bowel diseases. AB - Inflammatory bowel diseases (IBDs) are chronic and involve the gastrointestinal tract; the two primary IBDs are ulcerative colitis and Crohn's disease. Existing treatments for IBD include control of active inflammation and regulation of immune disorders, and commonly used drugs include salicylates, corticosteroids, and immunosuppressants. At the same time, an in-depth study of IBD pathogenesis promoted the acceptance of bioimmunotherapy by increasing numbers of people. However, long-term use of these drugs can cause adverse reactions that are difficult for patients to overcome, with limited efficacy for critically ill patients. Recent studies have found that stem cell transplantation is a new and effective therapy and IBD treatment, particularly for refractory cases. Stem cells, especially induced pluripotent stem cells (iPSCs), can differentiate into functional intestinal epithelia and their use avoids ethical issues arising from embryonic stem cells, providing a new kind of seed cell for alternative treatments for IBD. This paper reviews iPSCs as a potential new treatment for IBDs in order to provide an experimental and clinical reference. PMID- 25138008 TI - The composition of WHO's expert committee on essential medicines needs more scrutiny. PMID- 25138009 TI - Egg-yolk protein by-product as a source of ACE-inhibitory peptides obtained with using unconventional proteinase from Asian pumpkin (Cucurbita ficifolia). AB - In the present study angiotensin I-converting enzyme (ACE) inhibitory peptides were isolated from egg-yolk protein preparation (YP). Enzymatic hydrolysis conducted using unconventional enzyme from Cucurbita ficifolia (dose: 1000 U/mg of hydrolyzed YP (E/S (w/w)=1:7.52)) was employed to obtain protein hydrolysates. The 4-h hydrolysate exhibited a significant (IC50=482.5 MUg/mL) ACE inhibitory activity. Moreover, hydrolysate showed no cytotoxic activity on human and animal cell lines which makes it a very useful multifunctional method for peptide preparation. The compiled isolation procedure (ultrafiltration, size-exclusion chromatography and RP-HPLC) of bioactive peptides from YP hydrolysate resulted in obtaining peptides with the strong ACE inhibitory activity. One homogeneous and three heterogeneous peptide fractions were identified. The peptides were composed of 9-18 amino-acid residues, including mainly arginine and leucine at the N terminal positions. To confirm the selected bioactive peptide sequences their analogs were chemically synthesized and tested. Peptide LAPSLPGKPKPD showed the strongest ACE inhibitory activity, with IC50 value of 1.97 MUmol/L. BIOLOGICAL SIGNIFICANCE: Peptides with specific biological activity can be used in pharmaceutical, cosmetic or food industries. Because of their potential role as physiological modulators, as well as theirhigh safety profile, they can be used as natural pharmacological compounds or functional food ingredients. The development of biotechnological solutions to obtain peptides with desired biological activity is already in progress. Studies in this area are focused on using unconventional highly specific enzymes and more efficient methods developed to conduct food process technologies. Natural peptides have many advantages. They are mainly toxicologically safe, have wide spectra of therapeutic actions, exhibit less side effects compared to synthetic drugs and are more efficiently absorbed in the intestinal tract. The complexity of operation of large scale technologies and high cost of purification techniques are limiting factors to the commercialization of food-derived bioactive peptides. Research on the isolation of bioactive peptides in order to reduce the processing time and costs is continuously developing. Bioactive peptides can also be released from protein by products of the food industry, which reduce the substrate expense and production cost as well as provide the added advantage of an efficient waste disposal. Moreover, proteins as precursors of food-derived peptides are well-tolerated by the human body and therefore their application in drug development may reduce costs and duration of toxicological studies during research, development and clinical trials. PMID- 25138012 TI - Cross-national comparison of job satisfaction in doctors during economic recession. AB - BACKGROUND: Job satisfaction in doctors is related to migration, burnout, turnover and health service quality. However, little is known about their job satisfaction during economic recessions. Iceland and Norway have similar health care systems, but only Iceland was affected severely by the 2008 economic crisis. AIMS: To examine job satisfaction in Icelandic and Norwegian doctors, to compare job satisfaction with Icelandic data obtained before the current recession and to examine job satisfaction in response to cost-containment initiatives. METHODS: A survey of all doctors working in Iceland during 2010, a representative comparison sample of Norwegian doctors from 2010 and a historic sample of doctors who worked at Landspitali University Hospital in Iceland during 2003. The main outcome measure was job satisfaction, which was measured using a validated 10-item scale. RESULTS: Job satisfaction levels in Icelandic doctors (response rate of 61%, n = 622/1024), mean = 47.7 (SD = 10.9), were significantly lower than those of Norwegian doctors (response rate of 67%, n = 1025/1522), mean = 53.2 (SD = 8.5), after controlling for individual and work-related factors. Doctors at Landspitali University Hospital (response rate of 59%, n = 345/581) were less satisfied during the recession. Multiple regression analysis showed that cost-containment significantly affected job satisfaction (P < 0.001). CONCLUSIONS: Job satisfaction in doctors was lower in Iceland than in Norway, which may have been attributable partly to the current economic recession. PMID- 25138013 TI - The prevalence of respiratory symptoms among mushroom workers in Ireland. AB - BACKGROUND: Respiratory conditions such as asthma, bronchitis, hypersensitivity pneumonitis and upper airways symptoms have been ascribed to fungal exposures. Mushroom workers may be at risk of these as a consequence. AIMS: To assess the prevalence of respiratory symptoms in mushroom workers. METHODS: A cross sectional study assessed 4 weeks of respiratory symptoms among mushroom workers divided into four categories of exposure, using a self-administered respiratory questionnaire and spirometry. RESULTS: The population of 191 subjects was predominantly (66%) from Eastern Europe; 61% were women and 39% were under 30. It included 73 growers, 38 composters, 26 administrators and 52 packers. Among all workers, there was a high prevalence (67%) of one or more respiratory symptoms which did not appear to vary by age, gender, pack-years of smoking or duration of employment. There was a significant improvement in respiratory symptoms in workers during absence from the workplace (P < 0.001). Spirometry readings across all groups were within normal values. Symptom profiles suggest that as many as 22 workers had symptoms of airways disease; 18 (82%) of these were mushroom growers. Growers were significantly more likely to have symptoms consistent with airways disease than all other workers, odds ratio 9.2 (95% CI 3.0-28.4). CONCLUSIONS: There was a high prevalence of respiratory symptoms among mushroom workers. Mushroom growers may be at high risk of airways disease, possibly from fungal antigens or related exposures. PMID- 25138014 TI - An overview of the sequence features of N- and C-terminal segments of the human chemokine receptors. AB - Chemokine receptors play a crucial role in the cellular signaling enrolling extracellular ligands chemotactic proteins which recruit immune cells. They possess seven trans-membrane helices, an extracellular N-terminal region with three extracellular hydrophilic loops being important for search and recognition of specific ligand(s), and an intracellular C-terminal region with three intracellular loops that couple G-proteins. Although the functional aspects of the terminal segments of the extra-and intra-cellular G proteins are universally identified, the molecular basis on which they rest are still unclear because they are not definable by means of X-rays due to their high mobility and are not easy to study in the membrane. The purpose of this work is to define which physical chemical properties of the terminal segments of the human chemokine receptors are at the basis of their functional mechanisms. Therefore, we have evaluated their physical-chemical properties in terms of amino acid composition, local flexibility, disorder propensity, net charge distribution and putative sites of post-translational modifications. Our results support the conclusion that all 19 C-terminal and N-terminal segments of human chemokine receptors are very flexible due to the systematic presence of intrinsic disorder. Although, the purpose of this plasticity clearly appears that of controlling and modulating the binding of ligands, we provide evidence that the overlap of linearly charged stretches, intrinsic disorder and post-translational modification sites, consistently found in these motives, is a necessary feature to exert the function. The role of the intrinsic disorder has been discussed considering the structural information coming from intrinsically disordered model compounds which support the view that the chemokine terminals have to be considered as strong polyampholytes or polyelectrolytes where conformational ensembles and structural transitions between them are modulated by charge fraction variations. Also the role of post translational modifications has been found coherent with this view because, changing the charge fraction, they guide structural transitions between ensembles. Moreover, we have also considered our results from an evolutionary point of view in order to understand if the features found in humans were also present in other species. Our data evidenced that the structural features of the human terminals of the chemokine receptors were shared and evolutionarily conserved particularly among mammals. This means that the various organisms not only tolerate but select intrinsic disorder for the terminal regions of their receptors, reflecting constraints that point to molecular recognition. In conclusion the terminal segments of chemokine receptors must be considered as strong polyampholytes where the charge fraction variations induced by post translational modifications are the driving physico-chemical feature able to adapt the conformations of the terminal segments to their functions. PMID- 25138015 TI - Development of a cytokine-producing immortalized murine Kupffer cell line. AB - Kupffer cells (KC) play a critical role in both liver physiology and the pathogenesis of various liver diseases. Isolated primary KC have a limited lifespan in culture, and due to the relatively low number obtained, limit their study in vitro. Here, a cytokine-producing immortalized KC (ImKC) line was established from transgenic mice that express the thermolabile mutant tsA58 of the Simian virus 40 large T antigen under the control of the H-2k(b) promoter. Primary KC were obtained using a three step procedure: liver perfusion, centrifugal elutriation, and sorting for F4/80+ cells. ImKC were identified within the small-intermediate population of KC that maintained stable expression of F4/80, and the surface antigens CD11b, CD14 and TLR4. ImKC grow at IFNgamma independent manner at 37 degrees C and exhibited a doubling time of ~24 h when cultured in RPMI 1640 with 5% FBS. Our observations indicate that both activation of telomerase and expression of P53 are markedly increased, suggesting that enhanced telomerase activity and P53 expression may contribute to the immortalization of this cell population. ImKC cells maintained a high capacity to phagocytose FITC-latex beads, and bind/phagocytose erythrocytes. In addition, similar to primary KC, ImKC responded to stimulation with lipopolysaccharide (LPS: 0.1-1MUg/ml) by upregulating mRNA levels of TNFalpha (23-fold), IL-6 (28 fold), and IL-1beta (1459-fold), as measured by qRT-PCR. Protein levels of TNFalpha and IL-6 were also increased, 10-fold and 12-fold, respectively. Reactive oxygen species (ROS) and nitric oxide (NO) production were significantly enhanced in ImKC following an LPS challenge. Furthermore, LPS elicited a marked increase in mitogen activated protein kinase (MAPK) phospho-(ERK1/2, JNK) and NF kappaB p50 with decreased IkappaBalpha in ImKC, as assessed by Western blot. Collectively, these results demonstrate that the ImKC line retains critical characteristics of primary KC, and thus provides a useful tool to assess the role of KC in liver injury and chronic diseases. PMID- 25138016 TI - Serum cytokine profiles of Khorasan veterans 23 years after sulfur mustard exposure. AB - Sulfur mustard (SM) is an incapacitating chemical warfare agent that was used against Iranian soldiers during the period from 1983 to 1988. We have investigated serum cytokines profiles of Khorasan veterans who were exposed to SM >23 years earlier. Forty-four male Iranian veterans who had >40% disabilities due to delayed complications of SM poisoning and had disabilities were investigated. A total of 30 healthy male volunteers (relatives of the veterans) were selected as the control group. Cytokine levels were measured in the serum of case and control subjects using commercial ELISA kits. Hematologic parameters (white/red blood cell counts, hemoglobin levels, immune cell differentials) were also performed on blood samples from the study subjects. The results indicated that serum levels of ICAM-1 were significantly higher in the samples from SM-exposed veterans (772.8 [+/- 15.1] ng/ml [p=0.014] vs. control values of 710.2 [+/- 20.0] ng/ml). On the other hand, serum IL-1beta, IL-8 levels and TNFalpha, were significantly lower for the veterans than the controls (IL-1beta: 3.8 [+/- 0.1] vs. 4.3 [+/- 0.2] pg/ml, p=0.037; IL-8: 21.0 [+/- 6.1] vs. 84.6 [+/- 20.3] pg/ml, p=0.002; TNFalpha: 4.5 [+/- 0.1] vs. 5.5 [+/- 0.1] pg/ml, p=0.027). Levels of other assayed cytokines, e.g., IL-2, -4, -5, -6, -10, and -12, IFNgamma, TNFbeta, and sVCAM-1 were not significantly different between the study populations. None of the assayed hematologic parameters appeared to differ as well. It seems possible that dysfunctions could have been induced in the innate immune functions of the SM-exposed veterans as a result of these changes in cytokine expression and that these, in turn, may have contributed to the increased incidence of a myriad of diseases that have been documented in these veterans, including cancers. Future studies must focus on examining the significance of these changes in circulating cytokines and their potential contribution to the development of different diseases in veterans exposed to SM. PMID- 25138017 TI - Interleukin-28A enhances autoimmune disease in a retinal autoimmunity model. AB - Interleukin-28A (IL-28A), a member of type III interferons (IFN-lambdas), promotes antiviral, antitumor and immune responses. However, its ability to regulate autoimmune diseases is poorly understood. In this study, we examined the effect of IL-28A on retinal antigen-induced experimental autoimmune uveoretinitis (EAU), a mouse model of human T-cell-mediated autoimmune eye disease. We found that administration of IL-28A enhanced EAU scores and autoimmune response parameters including delayed-type hypersensitivity (DTH), Ag-specific T cell proliferation and the production of Ag-specific IL-17 and IFN-gamma in the priming phase. The effect of IL-28A was abrogated by administration of a neutralizing antibody against IL-28A. Our results suggest that IL-28A is capable of exacerbating a T-cell-mediated autoimmune disease. Thus, targeting IL-28A may provide a new therapeutic approach to T cell-mediated autoimmune diseases such as uveitis. PMID- 25138018 TI - Bone marrow involvement of Langerhans cell histiocytosis: immunohistochemical evaluation of bone marrow for CD1a, Langerin, and S100 expression. AB - AIMS: Although bone marrow (BM) involvement in Langerhans cell histiocytosis (LCH) is a negative prognostic indicator, there are no widely accepted criteria to define BM involvement in LCH. We evaluated the BM of LCH patients at diagnosis by immunohistochemical (IHC) staining for S100, CD1a and Langerin, along with other features. METHODS AND RESULTS: We retrospectively reviewed the records of 75 patients diagnosed as LCH at our center. IHC stains of Langerin, CD1a and S100 were done using paraffin-embedded tissue sections. Only three cases showed massive involvement of clustered Langerhans cells. There were linear associations between positive cell count and disease extent. Some discordant results between Langerin and CD1a IHC stains were noted. Among cases showing positive results for all three IHC stains, six patients (54.5%) were in the multisystem group, and three patients (27.3%) had cytopenias. The reactivation-free survival rates did not differ between the group positive for CD1a or Langerin, and the group negative for Langerin and CD1a. CONCLUSIONS: Langerin and CD1a seem to be useful markers of Langerhans cells, and S100 might be a nonspecific marker for these cells, in the BM. Both Langerin and CD1a IHC staining is needed to evaluate the BM involvement of LCH. PMID- 25138019 TI - An online version of the Mooney Face Test: phenotypic and genetic associations. AB - The Mooney Face Test is a widely used test of face perception, but was originally designed to be administered by personal interview. We have developed a three alternative forced-choice version for online testing. We tested 397 healthy adults between the ages of 18 and 42 (M=24 years). There was a wide range of performance (64-100% correct; M=89.6%). We observed a significant sex difference favoring males (.31 standard deviation; p =.004). In addition, independently of sex, higher 2D:4D digit ratios were significantly associated with higher scores (rho=.14, p=.006). A genome-wide association study (GWAS) for a subset of 370 participants identified an association between Mooney performance and a polymorphism in the RAPGEF5 gene (rs1522280; p=9.68*10(-8)). This association survives a permutation test (p=.031). PMID- 25138020 TI - Repeating pulmonary rehabilitation: prevalence, predictors and outcomes. AB - BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation (PR) is a cornerstone of care in chronic respiratory diseases; yet its benefits diminish over time. Repeating PR may be beneficial; however, little is known about the characteristics and outcomes of repeaters. This study aimed to establish the proportion of repeaters, identify characteristics that predict repetition and compare the magnitude of benefits achieved between initial and subsequent programmes. METHODS: Patients with stable chronic respiratory diseases who attended PR over a 9-year period were included. Outcome measures included the 6-min walk distance (6MWD) and the Chronic Respiratory Disease Questionnaire-Self-Reported (CRDQ-SR). Independent predictors of repeating were identified. RESULTS: Of 296 patients, 59 (20%) repeated PR, most within 1-3 years. Following the initial programme, repeaters had significant decline in 6MWD (-96.1 +/- 84.6 m; P < 0.001) and CRDQ-SR scores (mean decline -3.6 points, range -0.1 to -7.9 points; P < 0.005). The improvement in 6MWD was less in the repeat programme compared with the first (38.4 +/- 50.7 m vs 67 +/- 40.4 m; P = 0.005), while the change in CRDQ-SR was similar in all domains. A chronic obstructive pulmonary disease diagnosis increased the odds of repeating PR (odds ratio (OR) 4.8; P = 0.005) while improved mastery in the initial programme reduced the odds (OR 0.9; P = 0.033). CONCLUSIONS: One in five patients repeated PR, achieving clinically significant improvements in exercise tolerance and quality of life. Patients with small improvements in disease mastery after initial PR were more likely to repeat the programme and may benefit from earlier intervention or longer duration PR. PMID- 25138022 TI - Coadministrating luteolin minimizes the side effects of the aromatase inhibitor letrozole. AB - Aromatase inhibitors (AIs) have been used as adjuvant therapeutic agents for breast cancer. Their adverse side effect on blood lipid is well documented. Some natural compounds have been shown to be potential AIs. In the present study, we compared the efficacy of the flavonoid luteolin to the clinically approved AI letrozole (Femara; Novartis Pharmaceuticals, East Hanover, NJ) in a cell and a mouse model. In the in vitro experimental results for aromatase inhibition, the Ki values of luteolin and letrozole were estimated to be 2.44 uM and 0.41 nM, respectively. Both letrozole and luteolin appeared to be competitive inhibitors. Subsequently, an animal model was used for the comparison. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. Luteolin was given by mouth at 5, 20, and 50 mg/kg, whereas letrozole was administered by intravenous injection. Similar to letrozole, luteolin administration reduced plasma estrogen concentrations and suppressed the xenograft proliferation. The regulation of cell cycle and apoptotic proteins-such as a decrease in the expression of Bcl-xL, cyclin-A/D1/E, CDK2/4, and increase in that of Bax-was about the same in both treatments. The most significant disparity was on blood lipids. In contrast to letrozole, luteolin increased fasting plasma high-density lipoprotein concentrations and produced a desirable blood lipid profile. These results suggested that the flavonoid could be a coadjuvant therapeutic agent without impairing the action of AIs. PMID- 25138023 TI - [Burnout among high school students and tobacco use]. PMID- 25138021 TI - Thrombin inhibition with dabigatran protects against high-fat diet-induced fatty liver disease in mice. AB - Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of obesity and metabolic syndrome. Robust coagulation cascade activation is common in obese patients with NAFLD. We identified a critical temporal relationship between thrombin generation and the manifestation of hepatic steatosis, inflammation, and injury in C57BL/6J mice fed a high-fat diet (HFD) for 1, 2, and 3 months. Mice fed a HFD exhibited dramatic increases in hepatocellular injury and inflammation over time. Hepatic fibrin deposition preceded an increase in serum alanine aminotransferase, and the most dramatic changes in liver histopathology occurred in conjunction with a detectable increase in plasma thrombin-antithrombin levels at 3 months. To directly determine whether thrombin activity promotes NAFLD pathogenesis, mice were fed a HFD and simultaneously treated with the direct thrombin inhibitor dabigatran etexilate for 3 months. Notably, dabigatran treatment significantly reduced hepatic fibrin deposition, hepatic inflammation, hepatocellular injury, and steatosis in mice fed a HFD. Of interest, dabigatran treatment also significantly attenuated HFD-induced body weight gain. Gene expression analysis suggested that thrombin potentially drives NAFLD pathogenesis by altering the expression of genes associated with lipid metabolism and bile acid synthesis. Collectively, the results suggest that thrombin activity is central to HFD-induced body weight gain, liver injury, and inflammation and provide the proof-of-principle evidence that pharmacological thrombin inhibition could be effective in limiting NAFLD and associated pathologies. PMID- 25138024 TI - Urinary metabolomics for noninvasive detection of borderline and acute T cell mediated rejection in children after kidney transplantation. AB - The goal of this study was to evaluate the utility of urinary metabolomics for noninvasive diagnosis of T cell-mediated rejection (TCMR) in pediatric kidney transplant recipients. Urine samples (n = 277) from 57 patients with surveillance or indication kidney biopsies were assayed for 134 unique metabolites by quantitative mass spectrometry. Samples without TCMR (n = 183) were compared to borderline tubulitis (n = 54) and TCMR (n = 30). Partial least squares discriminant analysis identified distinct classifiers for TCMR (area under receiver operating characteristic curve [AUC] = 0.892; 95% confidence interval [CI] 0.827-0.957) and borderline tubulitis (AUC = 0.836; 95% CI 0.781-0.892), respectively. Application of the TCMR classifier to borderline tubulitis samples yielded a discriminant score (-0.47 +/- 0.33) mid-way between TCMR (-0.20 +/- 0.34) and No TCMR (-0.80 +/- 0.32) (p < 0.001 for all comparisons). Discriminant scoring for combined borderline/TCMR versus No TCMR (AUC = 0.900; 95% CI 0.859 0.940) applied to a validation cohort robustly distinguished between samples with (-0.08 +/- 0.52) and without (-0.65 +/- 0.54, p < 0.001) borderline/TCMR (p < 0.001). The TCMR discriminant score was driven by histological t-score, ct-score, donor-specific antibody and biopsy indication, and was unaffected by renal function, interstitial or microcirculatory inflammation, interstitial fibrosis or pyuria. These preliminary findings suggest that urinary metabolomics is a sensitive, specific and noninvasive tool for TCMR identification that is superior to serum creatinine, with minimal confounding by other allograft injury processes. PMID- 25138025 TI - Inflammation and immune system activation after traumatic brain injury. AB - Treatment options for managing traumatic brain injury remain limited. Therapies that limit the development of secondary brain injury--the delayed injury that can occur days to weeks after initial presentation--would have a major impact on outcomes and reduce the medical, social, and economic burden of this devastating disease. A growing body of evidence suggests that inflammation and activation of the immune system is a central driver of secondary brain injury. This article reviews the evidence for inflammation mediating secondary injury after head trauma and outlines potential approaches for immunomodulatory therapies after traumatic brain injury. PMID- 25138028 TI - The challenge: do pharmaceuticals present a risk to the environment, and what needs to be done to answer the question? PMID- 25138027 TI - In response: industry perspective. PMID- 25138026 TI - Endogenous retrovirus-K and nervous system diseases. AB - A new appreciation of the microbiome is changing the way we perceive human health and disease. The holobiontic nature of humans is even etched into our DNA in the form of viral symbionts. Empirical evidence for the presence of endogenous retroviruses (ERVs) in the human genome and their activity in homeostatic and pathologic states has accumulated; however, no causal relationship with human disease has been established to date. In this review, we will focus on the role of endogenous retrovirus-K in neurologic disease. Specifically, we will attempt to reconcile the pathologic contribution of ERVK in disparate neurologic diseases by providing evidence as to inter-individual differences in ERVK genotypes, addressing the molecular regulation of ERVK, and provide detailed examples of ERVK-mediated processes in nervous system diseases. PMID- 25138029 TI - In response: governmental perspective. PMID- 25138030 TI - Thrombospondin-1 is produced by retinal glial cells and inhibits the growth of vascular endothelial cells. AB - BACKGROUND/AIMS: By the release of antiangiogenic factors, Muller glial cells provide an angiostatic environment in the normal and ischemic retina. We determined whether Muller cells produce thrombospondin-1 (TSP-1), a known inhibitor of angiogenesis. METHODS: Secretion of TSP-1 by cultured Muller cells was determined with ELISA. Slices of rat retinas and surgically excised retinal membranes of human subjects were immunostained against TSP-1 and the glial marker vimentin. The effects of TSP-1 on the growth of bovine retinal endothelial cells (BRECs) and activation of ERK1/2 were determined with DNA synthesis and migration assays, and Western blotting, respectively. RESULTS: Cultured Muller cells secrete TSP-1 under normoxic and hypoxic (0.2% O2) conditions. Secretion of TSP-1 was increased in hypoxia compared to normoxia. In rat retinal slices, glial, retinal ganglion, and possibly horizontal cells were stained for TSP-1. Retinal glial cells in preretinal membranes from human subjects with nonhypoxic epiretinal gliosis (macular pucker) and proliferative diabetic retinopathy, respectively, were immunopositive for TSP-1. Exogenous TSP-1 reduced the VEGF induced proliferation and migration of BRECs and decreased the phosphorylation level of ERK1/2 in BRECs. CONCLUSION: The data suggest that Muller cells are one major source of TSP-1 in the normal and ischemic retina. Glia-derived TSP1 may inhibit angiogenic responses in the ischemic retina. PMID- 25138031 TI - Lutecium fluoride hollow mesoporous spheres with enhanced up-conversion luminescent bioimaging and light-triggered drug release by gold nanocrystals. AB - Uniform Na5Lu9F32 hollow mesoporous spheres (HMSs) have been successfully prepared by a facile and mild (50 degrees C for 5 h) coprecipitation process, and Au nanocrystals (NCs) with particle size of about 10 nm were conjugated to poly(ether imide) (PEI) modified HMSs by electrostatic interaction. Compared with Na5Lu9F32:Yb/Er HMSs, the up-conversion (UC) luminescence intensity of Na5Lu9F32:Yb/Er@Au HMSs was much higher under low pump power due to the local field enhancement (LFE) of Au NCs, and there is a surface plasmon resonance (SPR) effect with nonradiative transitions which generates a thermal effect. These two effects have been proved by theoretical discrete-dipole approximation (DDA) simulation. The good biocompatibility of Na5Lu9F32:Yb/Er@Au HMSs indicates them as a promising candidate in the biological field. Particularly, under near infrared (NIR) laser irradiation, a rapid doxorubicin (DOX) release was achieved due to the thermal effect of Au NCs. In this case, Na5Lu9F32:Yb/Er@Au HMSs exhibit an apparent NIR light-controlled "on/off" drug release pattern. In addition, UC luminescent images uptaken by cells show brighter green and red emission under NIR laser excitation. Therefore, this novel multifunctional (mesoporous, enhanced UC luminescent, and light-triggered drug release) material should be potential as a suitable targeted cancer therapy carrier and bioimaging. PMID- 25138034 TI - Coronary artery tortuosity in spontaneous coronary artery dissection: angiographic characteristics and clinical implications. AB - BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic cause of acute coronary syndrome. The angiographic characteristics of SCAD are largely undetermined. The goal of this study was to determine the prevalence of coronary tortuosity in SCAD and whether it may be implicated in the disease. METHODS AND RESULTS: Patients with confirmed SCAD (n=246; 45.3+/-8.9 years; 96% women) and 313 control patients without SCAD or coronary artery disease who underwent coronary angiography were included in this case-control study. Angiograms were reviewed for coronary tortuosity and assigned a tortuosity score. Tortuosity was common in patients presenting with their first SCAD event (78% versus 17% in controls; P<0.0001; tortuosity score, 4.41+/-1.73 versus 2.33+/-1.49 in controls; P<0.0001) despite a low prevalence of hypertension (34%). Recurrent SCAD (n=40) occurred within segments of tortuosity in 80% of cases. Severe tortuosity (>=2 consecutive curvatures >=180 degrees ) was associated with a higher risk of recurrent SCAD (hazard ratio, 3.29; 95% confidence interval, 0.99-8.29; P=0.05). Tortuosity score >5 was associated with a trend toward higher risk of recurrent SCAD (P=0.16). Prespecified angiographic markers of tortuosity including corkscrew appearance and multivessel symmetrical tortuosity were associated with extracoronary vasculopathy including fibromuscular dysplasia (P<0.05 for both). CONCLUSIONS: Coronary artery tortuosity is highly prevalent in the SCAD population and is associated with recurrent SCAD. Recurrent SCAD most often occurs within segments of tortuosity. Angiographic features of SCAD are associated with extracoronary vasculopathy, including fibromuscular dysplasia. These findings suggest that coronary tortuosity may serve as a marker or potential mechanism for SCAD. PMID- 25138035 TI - Effect of single tibial artery revascularization on microcirculation in the setting of critical limb ischemia. AB - BACKGROUND: Benefits of 2-dimensional (2D) angiosome-oriented infrapopliteal revascularization remain controversial. The aim of this retrospective study was to clarify the effect of single tibial artery revascularization on the dorsal and plantar microcirculation of critically ischemic limbs based on skin perfusion pressure (SPP). METHODS AND RESULTS: Fifty-seven interventions that only involved either anterior tibial artery (ATA) or posterior tibial artery (PTA) revascularization were included in this study. SPP was measured on the dorsal side (theoretically ATA perfusion area) and the plantar side (theoretically PTA perfusion area) before and after the procedure. Dorsal and plantar SPP increased significantly, from 33 (IQR 23-40.5) to 52 (IQR 32.5-65) mm Hg (P<0.0001) and 31.6+/-16.1 to 44.8+/-19.2 mm Hg (P=0.001) after ATA revascularization, respectively, and from 29.3+/-14.0 to 42.4+/-19.7 mm Hg (P=0.003) and 29.3+/-9.8 to 43.5+/-15.9 mm Hg (P<0.001) after PTA revascularization, respectively. Both ATA and PTA revascularization were not associated with any significant differences in DeltaSPP between the dorsal and the plantar regions of the foot. Only 64% and 58% of ATA revascularization cases showed higher post-SPP and DeltaSPP on the dorsal side than on the plantar side, respectively. Also, only 47% and 40% of PTA revascularization cases showed higher post-SPP and DeltaSPP on the plantar side than on the dorsal side, respectively. CONCLUSIONS: Single tibial artery revascularization, whether of the ATA or PTA, yielded comparable improvements in microcirculation of the dorsal and plantar foot. Approximately half of the feet revascularized had a change in microcirculation that was not consistent with the 2D angiosome theory. PMID- 25138036 TI - Management and outcome of metastatic clear cell sarcoma. PMID- 25138037 TI - Treatment of fracture sequelae of the proximal humerus: comparison of hemiarthroplasty and reverse total shoulder arthroplasty. AB - INTRODUCTION: Fracture sequelae (FS) of the proximal humerus is a challenging scenario in shoulder surgery. Despite they have been traditionally treated with hemiarthroplasty (HA), the use of reverse shoulder arthroplasty (RSA) has been recently introduced. However, there are no studies comparing the results of HA and RSA in FS. The purpose of this study was to compare the functional and quality of life-related outcomes, and complications in the treatment of proximal humeral FS between HA and RSA. MATERIALS AND METHODS: A therapeutic prospective non-randomized comparative study was conducted. All consecutive patients with diagnosis of FS after non-operative treatment of proximal humeral fractures and no previous shoulder surgery were considered for this study. A total of 32 patients (24 females, 8 males) with a mean (SD) age at the time of surgery of 80.1 (4.9) years were finally included: 12 in the HA group, and 20 in the RSA group. FS were treated with shoulder arthroplasty by the implantation of either HA or RSA. Constant score (total and specific items), quality of life (assessed through SF-36), and complications requiring revision surgery were compared between groups. RESULTS: All parameters of the Constant score significantly improved in the postoperative compared to preoperative period when considering the entire sample. The RSA group demonstrated a higher improvement in total Constant score (p = 0.06) and Constant activity level (p = 0.02) compared to the HA group. The HA demonstrated a higher number of complications compared to the RSA (p = 0.05). There were no differences in SF-36 scores between both groups. CONCLUSIONS: The shoulder arthroplasty is an effective treatment for FS with significant improvement in pain and function. The RSA may be a better option than HA for FS given the trend towards better total Constant score and a significantly lower number of complications requiring revision surgery. LEVEL OF EVIDENCE: Therapeutic level II evidence. PMID- 25138038 TI - Effects of diesel and kerosene on germination and growth of coastal wetland plant species. AB - This study aims to investigate effects of diesel and kerosene on seed germination and seedling growth among coastal wetland plants to select species that can be used for the restoration and revegetation of oil-polluted habitats. Tests on 51 species were performed in Petri dishes containing 0 %, 6 %, 12 %, and 18 % diesel, 20 %, 40 %, and 60 % kerosene; each treatment combination was replicated five times with 20 seeds in each Petri dish. All dishes were held in a growth chamber with 20 degrees C day of 12 h/15 degrees C night of 12 h in 80 % humidity for 20 days for calculating the germination percentage, seedling weight, and seedling vitality. The germination percentage of Rumex stenophyllus decreased significantly in diesel and kerosene treatments. The weights of seedlings treated with diesel and kerosene either increased or decreased in comparison with controls depending on the species. Vitality percentage values were high for seedlings of Chenopodium ficifolium. Thus, herbaceous plant responses to oil treatments are species-specific. PMID- 25138039 TI - Prevalence comparisons of somatic and psychiatric symptoms between community nonpatients without pain, acute pain patients, and chronic pain patients. AB - OBJECTIVES: Somatic/psychiatric symptoms are frequently found in chronic pain patients (CPPs). The objectives of this study were to determine 1) which somatic/psychiatric symptoms are more commonly found in acute pain patients (APPs) and CPPs vs community nonpatients without pain (CNPWPs) and 2) if somatic/psychiatric symptom prevalence differs between APPs and CPPs. DESIGN: The above groups were compared statistically for endorsement of 15 symptoms: fatigue, numbness/tingling, dizziness, difficulty opening/closing mouth, muscle weakness, difficulty staying asleep, depression, muscle tightness, nervousness, irritability, memory, falling, nausea, concentration, and headaches. RESULTS: After controlling for age, gender, and level of pain, APPs and CPPs had a statistically significantly greater prevalence (at a P < 0.01 level) for 11 and 13 symptoms, respectively, vs CNPWPs. After controlling for age, gender, and level of pain, CPPs had a statistically significantly greater prevalence (at a P < 0.01 level) for eight symptoms vs APPs. Symptoms were highly correlated in both APPs and CPPs. CONCLUSIONS: CPPs are characterized to a significantly greater extent than comparison groups by somatic/psychiatric symptoms that are highly intercorrelated. This has implications for clinical practice and future research. PMID- 25138040 TI - Using and interpreting serum albumin and prealbumin as nutritional markers in patients on chronic dialysis. PMID- 25138042 TI - Ser9-phosphorylated GSK3beta induced by 14-3-3zeta actively antagonizes cell apoptosis in a NF-kappaB dependent manner. AB - The activity of glycogen synthase kinase beta (GSK3beta) is mainly regulated by its Ser9 phosphorylation. It has been believed for a long time that Ser9 phosphorylation regulates the functions of GSK3beta through inhibition of its kinase activity. In this study, we have confirmed the interaction of Ser9 phosphorylated GSK3beta with 14-3-3zeta by using GST pull-down assays. We show that 14-3-3zeta enhances Ser9 phosphorylation of GSK3beta by PKC. Surprisingly, using a NF-kappaB luciferase reporter system, we find that Ser9-phosphorylation of GSK3beta promoted by 14-3-3zeta is critical for the activation of NF-kappaB pathway, which may thwart the pro-apoptotic activity of GSK3beta. Inhibition of either NF-kappaB or GSK3beta significantly abolishes the anti-apoptotic effect of 14-3-3zeta and Ser9-phosphorylated GSK3beta, suggesting that Ser9-phosphorylated GSK3beta actively antagonizes cell apoptosis in a NF-kappaB dependent manner. PMID- 25138041 TI - Influence of irradiation time on subsurface degree of conversion and microhardness of high-viscosity bulk-fill resin composites. AB - OBJECTIVES: To evaluate the influence of irradiation time on degree of conversion (DC) and microhardness of high-viscosity bulk-fill resin composites in depths up to 6 mm. MATERIALS AND METHODS: Four bulk-fill materials (Tetric EvoCeram Bulk Fill--TECBF; x-tra fil--XF; QuixFil--QF; SonicFill-SF) and one conventional nano hybrid resin composite (Tetric EvoCeram--TEC) were irradiated for 10, 20, or 30 s at 1,170 mW/cm(2). DC and Knoop microhardness (KHN) were recorded after 24-h dark storage at five depths: 0.1, 2, 4, 5, and 6 mm. Data were statistically analyzed using ANOVA and Bonferroni's post-hoc test (alpha = 0.05). RESULTS: With increasing bulk thickness, DC and KHN significantly decreased for TEC. TECBF and SF showed a significant decrease in DC and KHN at 4-mm depth after 10-s irradiation, but no decrease in DC after 30-s irradiation (p > 0.05). XF and QF demonstrated no significant DC decrease at depths up to 6 mm after irradiation of at least 20 s. At 4-mm depth, all materials tested achieved at least 80 % of their maximum DC value, irrespective of irradiation time. However, at the same depth (4 mm), only XF and QF irradiated for 30 s achieved at least 80 % of their maximum KHN value. CONCLUSIONS: Regarding DC, the tested bulk-fill resin composites can be safely used up to at least 4-mm incremental thickness. However, with respect to hardness, only XF and QF achieved acceptable results at 4-mm depth with 30 s of irradiation. CLINICAL RELEVANCE: Minimum irradiation times stated by the manufacturers cannot be recommended for placement of high-viscosity bulk-fill materials in 4-mm increments. PMID- 25138043 TI - The economic burden of time-loss injuries to youth players participating in week long rugby union tournaments. AB - OBJECTIVES: Rugby Union ("rugby") is a popular sport with high injury risk. Burden of injury is described by the incidence and severity of injury. However reports have ignored the monetary cost of injuries. Therefore the aim of this study was to describe the monetary cost associated with youth rugby injuries. DESIGN: This descriptive study quantified medical treatments of injured players at the South African Rugby Union Youth tournaments in 2011/2012 and the days of work parents missed as a result of the injuries. A health insurer used these data to calculate associated costs. METHODS: Legal guardians of the 421 injured players were contacted telephonically on a weekly basis until they returned to play. Treatments costs were estimated in South African Rands based on 2013 insurance rates and converted to US$ using purchasing power parities. RESULTS: Of the 3652 players, 2% (n=71) sought medical care after the tournament. For these players, average treatment costs were high (US$731 per player, 95% CI: US$425 US$1096), with fractures being the most expensive type of injury. Players with medical insurance had higher costs (US$937, 95% CI: US$486-US$1500) than those without (US$220, 95% CI: US$145-US$302). CONCLUSIONS: Although a minority of players sought follow-up treatment after the tournaments, the cost of these injuries was high. Players without medical insurance having lower costs may indicate that these players did not receive adequate treatment for their injuries. Injury prevention efforts should consider injuries with high costs and the treatment of players without medical insurance. PMID- 25138044 TI - The coupling of tautomerization to hydration in the transition state on the pyrimidine photohydration reaction path. AB - The ground state reaction path for formation of the pyrimidine hydrates was calculated using a nudged elastic band (NEB) approach, combined with a calculation of the transition state, and implemented using a numerical basis set in the density functional theory (DFT) code DMol(3). The model systems used for study consist of 1-methyl pyrimidines with a H2O molecule as the reactant, and the corresponding C5-hydro-C6-hydroxypyrimidine as the product. The barrier to addition of water across the C5-C6 pi-bond ranges from 43-48 kcal mol(-1) in the 1-methylpyrimidines (1-MP) studied. Similar but slightly smaller barriers of 34 45 kcal mol(-1) were found for the tautomers of the 1-MPs, i.e. the enols of uridine and thymine and imine of cytosine. Comparison of these calculations with previous computational and experimental work suggests that a hot ground state formed by the rapid internal conversion of pyrimidines has sufficient energy to permit crossover from the common form to the tautomeric form of the pyrimidine at the transition state. The hot ground state mechanism can account for the experimentally observed yield and thermal reversion of pyrimidine photohydrates, while simultaneously explaining the effect of photohydrates on the mutation rate. PMID- 25138045 TI - Effect of different assumptions for brain water content on absolute measures of cerebral oxygenation determined by frequency-domain near-infrared spectroscopy in preterm infants: an observational study. AB - BACKGROUND: Brain-water content (BWC) decreases with maturation of the brain and potentially affects parameters of cerebral oxygenation determined by near infrared spectroscopy (NIRS). Most commercially available devices do not take these maturational changes into account. The aim of this study was to determine the effect of different assumptions for BWC on parameters of cerebral oxygenation in preterm infants. METHODS: Concentrations of oxy-, deoxy- and total hemoglobin and regional cerebral oxygen saturation (rcStO2) were calculated based on absolute coefficients of absorption and scattering determined by multi-distance Frequency-Domain-NIRS assuming BWCs of 75-95%, which may be encountered in newborn infants depending on gestational and postnatal age. RESULTS: This range of BWC gave rise to a linear modification of the assessed NIRS parameters with a maximum change of 10%. This may result in an absolute overestimation of rcStO2 by (median (range)) 4 (1-8)%, if the calculation is based on the lowest BWC (75%) in an extremely preterm infant with an anticipated BWC of 95%. CONCLUSION: Clinicians wishing to rely on parameters of cerebral oxygenation determined by NIRS should consider that maturational changes in BWC not taken into account by most devices may result in a deviation of cerebral oxygenation readings by up to 8% from the correct value. PMID- 25138046 TI - Effect of atrazine and fenitrothion at no-observed-effect-levels (NOEL) on amphibian and mammalian corticosterone-binding-globulin (CBG). AB - This study determines the effect of atrazine and fenitrothion no-observed-effect levels (NOEL) on the binding of corticosterone (B) to corticosterone-binding globulin (CBG) in an amphibian and a mammal. Plasma from five cane toads and five Wistar rats was exposed to atrazine and fenitrothion at the NOEL approved for Australian fresh water residues and by the World Health Organization (WHO). The concentration required to displace 50% (IC50) of B binding to CBG was determined by a competitive microdialysis protein assay. Competition studies showed that both atrazine and fenitrothion at NOEL are able to compete with B for CBG binding sites in toad and rat plasma. The IC50 levels for atrazine in toads and rats were 0.004 nmol/l and 0.09 nmol/l respectively. In the case of fenitrothion the IC50 level found in toads was 0.007 nmol/l, and 0.025 nmol/l in rats. Plasma dilution curves showed parallelism with the curve of B, demonstrating that these agro chemicals are competitively inhibiting binding to CBG. The displacement of B by atrazine and fenitrothion would affect the total:free ratio of B and consequently disrupt the normal stress response. This is the first time that the potential disruptive effect of atrazine and fenitrothion on B-CBG interaction at the NOELs has been demonstrated in amphibian and mammalian models. PMID- 25138047 TI - The reliability of fetal MRI in the assessment of brain malformations. AB - OBJECTIVES: To assess the inter- and intraobserver reliability of different fetal MRI measurements in cases of fetal brain malformations and to examine the concordance between ultrasonography (US) and MRI findings. METHODS: Fetal brain MRIs and US findings of 56 pregnant women were retrieved from the institutional database. Standardized fetal brain MRI measurements were performed by 4 observers, and the inter- and intraobserver reliability was determined. Additionally, US and MRI findings were retrospectively compared. RESULTS: The interobserver intraclass correlation coefficient (ICC) was above 0.9 for the cerebellum and posterior horn of the lateral ventricle. The measurements regarding the third ventricle (0.50), the fourth ventricle (0.58), and the corpus callosum (0.63) showed poor reliability. Overall, the intraobserver reliability was greater than the interobserver reliability. US and MRI findings were discordant in 29% of the cases with MRI rendering an extended diagnosis in 18%, a change of diagnosis in 3.6%, and excluding pathological findings suspected on US in 7.1%. CONCLUSIONS: Fetal MRI is a valuable complement to US in the investigation of fetal brain malformations. The reliability of most parameters was high, except for the measurements of the third and fourth ventricles and the corpus callosum. PMID- 25138048 TI - Targeting primary mediastinal B-cell lymphoma. PMID- 25138049 TI - 'Sex' in the cancer cell. PMID- 25138050 TI - Deletion of Ptprd and Cdkn2a cooperate to accelerate tumorigenesis. AB - PTPRD encodes the protein tyrosine phosphatase receptor type D and is frequently inactivated across many human cancers. Despite its frequent inactivation, it is unknown whether loss of PTPRD promotes tumorigenesis in vivo. PTPRD is located on chromosome 9p, as is CDKN2A, and the two loci are frequently deleted together. Here, we show that co-deletion of Ptprd and Cdkn2a cooperate to accelerate tumorigenesis. Interestingly,heterozygous loss of Ptprd was sufficient to promote tumorigenesis in our model, suggesting that Ptprd may be a haploinsufficient tumor suppressor. The loss of Ptprd resulted in changes to the tumor spectrum in mice and increased the frequency of lymphomas. In total, we reveal that Ptprd is a tumor suppressor that can promote tumorigenesis in concert with Cdkn2a loss. PMID- 25138051 TI - Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL. AB - Bone homeostasis critically relies on the RANKL-RANK-OPG axis which can be targeted by the fully human monoclonal antibody denosumab in conditions with increased bone resporption such as bone metastases. The binding site and therefore the molecular mechanism by which this antibody inhibits RANKL has not been characterized so far. Here, we used random peptide phage display library screenings to identify the denosumab epitope on RANKL. Alignments of phage derived peptide sequences with RANKL suggested that this antibody recognized a linear epitope between position T233 and Y241. Mutational analysis confirmed the core residues as critical for this interaction. The spatial localization of this epitope on a 3-dimensional model of RANKL showed that it overlapped with the major binding sites of OPG and RANK on RANKL. We conclude that denosumab inhibits RANKL by both functional and molecular mimicry of the natural decoy receptor OPG. PMID- 25138054 TI - Recurrence of a Delayed-Onset Posttraumatic Renal Pseudoaneurysm after Initially Successful Transarterial Embolization. AB - Hemodynamically stable patients with renal injury can be managed conservatively. Anatomy typically leads to physiologic confinement of urinomas or renal hematomas to the interfascial planes of the retroperitoneum. In the presented case there was unusual reperfusion 14 days after a successful embolization of a renal pseudoaneurysm, at this time 28 days after the initiating trauma. This article discusses the evolution, treatment options and possible underlying causes for the reperfusion of this late-onset renal pseudoaneurysm. PMID- 25138052 TI - Inhibition of lung tumor growth by targeting EGFR/VEGFR-Akt/NF-kappaB pathways with novel theanine derivatives. AB - The molecularly targeted agents, including anti-VEGF or anti-EGFR monoclonal antibody and some inhibitors of EGFR tyrosine kinase, are effective in the treatment of non-small-cell lung cancer (NSCLC) to a certain extent, but the benefit for a proportion of patients is still limited. Hence, it is necessary and urgent to develop more selective and effective molecular targeted agents against lung cancer. Here, we have synthesized novel theanine derivatives, methyl coumarin-3-carboxylyl L-theanine (TMC), ethyl coumarin-3-carboxylyl L-theanine (TEC), ethyl 6-fluorocoumarin- 3-carboxylyl L-theanine (TFC), and ethyl 6 nitrocoumarin-3-carboxylyl L-theanine (TNC), which are fluorescent small molecules, based on their parental compound theanine and studied their anticancer activities in vitro, ex vivo and in vivo models of human and mouse cancers. Our results show that the four theanine derivatives significantly inhibit the lung cancer cell migration and the growth of lung cancer and leukemia cell lines. TFC and TNC display enhanced effects with anticancer drugs cytarabine vincristine, andmethotrexate on inhibition of lung cancer cell growth and no toxicity to the normal human embryonic lung fibroblast and peripheral blood lymphocytes. TFC and TNC exhibit strong suppression of the highly metastatic Lewis lung cancer (LLC) and A549 tumor growth in tumor-bearing mice without toxicity to mice. TFC and TNC can effectively suppress the growth of lung cancer cells in vitro, ex vivo and in vivo by targeting EGFR/VEGFR-Akt/NF-kappaB pathways. Our study has suggested that TFC and TNC may have the therapeutic and/or adjuvant therapeutic applications in the treatment of lung cancers and other cancer. PMID- 25138053 TI - Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma. AB - PURPOSE: Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid (ZOL) represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, ZOL triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), which could enhance tumor cell survival and treatment resistance. We hypothesized that targeting CLU using siRNA or the antisense drug, OGX-011, will suppress treatment-induced CLU induction and enhance ZOL-induced cell death in osteosarcoma (OS) cells. METHODS: The combined effects of OGX-011 and ZOL were investigated in vitro on cell growth, viability, apoptosis and cell cycle repartition of ZOL-sensitive or -resistant human OS cell lines (SaOS2, U2OS, MG63 and MNNG/HOS). RESULTS: In OS cell lines, ZOL increased levels of HSPs, especially CLU, in a dose- and time-dependent manner by mechanism including increased HSF1 transcription activity. The OS resistant cells to ZOL exhibited higher CLU expression level than the sensitive cells. Moreover, CLU overexpression protects OS sensitive cells to ZOL-induced cell death by modulating the MDR1 and farnesyl diphosphate synthase expression. OGX-011 suppressed treatment-induced increases in CLU and synergistically enhanced the activity of ZOL on cell growth and apoptosis. These biologic events were accompanied by decreased expression of HSPs, MDR1 and HSF1 transcriptional activity. In vivo, OGX-011, administered 3 times a week (IP, 20mg/kg), potentiated the effect of ZOL (s.c; 50ug/kg), significantly inhibiting tumor growth by 50% and prolonging survival in MNNG/HOS xenograft model compared to ZOL alone. CONCLUSION: These results indicate that ZOL-mediated induction of CLU can be attenuated by OGX-011, with synergistic effects on delaying progression of osteosarcoma. PMID- 25138056 TI - The psychometric properties of the St George's Respiratory Questionnaire (SGRQ) in patients with idiopathic pulmonary fibrosis: a literature review. AB - Assessment of health-related quality of life (HRQL) is particularly important in patients with progressive and incurable diseases such as idiopathic pulmonary fibrosis (IPF). The St George's Respiratory Questionnaire (SGRQ) has frequently been used to measure HRQL in patients with IPF, but it was developed for patients with obstructive lung diseases. The aim of this review was to examine published data on the psychometric performance of the SGRQ in patients with IPF. A comprehensive search was conducted to identify studies reporting data on the internal consistency, construct validity, test-retest reliability, and interpretability of the SGRQ in patients with IPF, published up to August 2013. In total, data from 30 papers were reviewed. Internal consistency was moderate for the SGRQ symptoms score and excellent for the SGRQ activity, impact and total scores. Validity of the SGRQ symptoms, activity, impact and total scores was supported by moderate to strong correlations with other patient-reported outcome measures and with a measure of exercise capacity. Most correlations were moderately strong between SGRQ activity or total scores and forced or static vital capacity, the most commonly used marker of IPF severity. There was evidence that changes in SGRQ domain and total scores could detect within-subject improvement in health status, and differentiate groups of patients whose health status had improved, declined or remained unchanged. Although the SGRQ was not developed specifically for use with patients with IPF, on balance, its psychometric properties are adequate and suggest that it may be a useful measure of HRQL in this patient population. However, several questions remain unaddressed, and further research is needed to confirm the SGRQ's utility in IPF. PMID- 25138057 TI - Serum microRNA-29 levels correlate with disease progression in patients with chronic hepatitis B virus infection. AB - OBJECTIVE: To investigate the role of serum microRNA-29 (miR-29) as a biomarker for the prediction of disease progression in patients with chronic hepatitis B virus (HBV) infection. METHODS: Using real-time quantitative polymerase chain reaction assay, serum miR-29a, miR-29b and miR-29c levels were measured in patients with chronic HBV infection, and the correlation between serum miR-29 levels and the participants' liver biochemistry, fibrotic stage and necroinflammation grade were also evaluated. RESULTS: Altogether 91 patients with chronic HBV infection were divided by fibrotic stage into S0/1 (no or mild fibrosis), S2/3 (progressive fibrosis) and S4 (cirrhosis) subgroups, and 12 healthy individuals were also included in the study. Serum miR-29a and miR-29c in S0-3 were significantly higher than those in S4 patients (P < 0.001); however, the difference between S0/1 and S2/3 patients was not significant. miR-29b levels were higher in S0/1 patients than in other patient groups, but did not differ between S2/3 and S4 patients. At fibrotic stages of S0/1 and S2/3, patients with no or mild liver inflammation (G0/1) tended to express higher miR-29 levels than those with advanced inflammation (G2-4) (P > 0.05). miR-29a-c showed significant correlation with alanine transaminase levels (P < 0.05 for miR-29a, miR-29b and miR-29c) in S0-3 patients. The expression of miR-29 was highest in immune tolerant patients (P < 0.001). CONCLUSIONS: Serum miR-29 levels are negatively correlated with liver fibrotic stages and necroinflammation grades in patients with chronic HBV infection. miR-29 appears to be a novel biomarkers for predicting disease progression in these patients. PMID- 25138055 TI - PET imaging in ischemic cerebrovascular disease: current status and future directions. AB - Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the final infarcts; this is also important for decisions concerning invasive therapy in large ("malignant") infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinflammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases. PMID- 25138058 TI - Ranolazine as a promising treatment option for atrial fibrillation: electrophysiologic mechanisms, experimental evidence, and clinical implications. AB - Currently available agents for pharmacologic management of atrial fibrillation (AF) are limited by their suboptimal efficacy and nonnegligible proarrhythmic risk. Ranolazine (RN) is a novel antianginal agent with increasingly appreciated antiarrhythmic properties that can suppress ventricular and supraventricular arrhythmias including AF. In this review, we describe the electrophysiological properties of RN, focusing on atrial-selective inhibition of a number of ion channels implicated in the development of AF, particularly the sodium current. We further summarize evidence from experimental studies that demonstrate a potent AF suppressing effect of RN, alone or in combination with other antiarrhythmic drugs. Of clinical relevance, we present growing evidence from preliminary clinical investigations indicating the safety and efficacy of RN for prevention and treatment of AF in various clinical settings including prevention of AF in patients with acute coronary syndromes, prevention and conversion of postoperative AF after surgical coronary revascularization, sinus rhythm maintenance in drug-resistant recurrent AF, and facilitating of electrical or pharmacological cardioversion in cardioversion-resistant patients. While current experimental and clinical evidence points to RN as a potentially promising agent for suppression of AF, well-designed, large-scale trials will be required before RN can be considered for pharmacological treatment of AF in clinical practice. PMID- 25138059 TI - Adolescent chronic pain and association to perinatal factors: linkage of Birth Registry data with the Young-HUNT Study. AB - BACKGROUND: The aim of this study was to examine the associations of birthweight, gestation and 5-min Apgar score with self-reported chronic nonspecific pain in a large, unselected adolescent population. METHODS: The third population-based Nord Trondelag Health Study (HUNT) included 8200 adolescents aged 13-19 years, constituting 78.2% of adolescents in Nord-Trondelag County. In the target age group, 13-18 years, data on pain frequency from 10 localizations were available from 7373 adolescents. Chronic nonspecific pain was defined as pain at least once a week during the last 3 months, not related to any known disease or injury. Chronic multisite pain was defined as chronic pain in at least three localizations, and chronic daily pain was defined as chronic pain almost every day. Perinatal data were retrieved from the Medical Birth Registry of Norway, and data were available for 7120 of the 7373 adolescents. Covariates included adolescent and maternal general health measures from the HUNT study. RESULTS: We found no consistent association between preterm birth and chronic pain and no clear association between birthweight and chronic pain complaints in adolescence. Post-term birth in boys and a low 5-min Apgar score in both sexes tended to increase the reporting of chronic pain in adolescence. CONCLUSIONS: Perinatal factors, and especially preterm birth and low birthweight, did not seem to have a major impact on pain complaints in adolescence. PMID- 25138061 TI - Pharmacokinetics and efficacy of darunavir/ritonavir once daily in virologically suppressed, treatment-experienced HIV-infected children. PMID- 25138062 TI - Acid-promoted chemoselective introduction of amide functionality onto aromatic compounds mediated by an isocyanate cation generated from carbamate. AB - Carbamates have been used as precursors of isocyanates, but heating in the presence of strong acids is required because cleavage of the C-O bond in carbamates is energy-demanding even in acid media. Direct amidation of aromatic compounds by isocyanate cations generated at room temperature from carbamoyl salicylates in trifluoromethanesulfonic acid (TfOH) was examined. Carbamates with ortho-salicylate as an ether group (carbamoyl salicylates) showed dramatically accelerated O-C bond dissociation in TfOH, which resulted in facile generation of the isocyanate cation. These chemoselective intermolecular aromatic amidation reactions proceeded even at room temperature and showed good compatibility with other electrophilic functionalities and high discrimination between N monosubstituted carbamate and N,N-disubstituted carbamate. The reaction rates of secondary and tertiary amide formation were markedly different, and this difference was utilized to achieve successive (tandem) amidation reactions of molecules with an N-monosubstituted carbamate and an N,N-disubstituted carbamate with two kinds of aromatic compounds. PMID- 25138060 TI - Star-shaped poly(L-lactide)-b-poly(lactobionamidoethyl methacrylate) with porphyrin core: synthesis, self-assembly, singlet oxygen research and recognition properties. AB - Star-shaped porphyrin-cored poly(L-lactide)-b-poly(lactobionamidoethyl methacrylate) block copolymers (SPPLA-b-PLAMA) were synthesized via RAFT of unprotected Lactobionamidoethyl methacrylate (LAMA) in 1-methyl-2-pyrrolidinone (NMP) solution at 70 degrees C. The structure of this as-synthesized SPPLA-b PLAMA block copolymer was thoroughly studied by nuclear magnetic resonance spectroscopy, gel permeation chromatography (GPC), and Fourier transforms infrared. Moreover, under the irradiation, such SPPLA-b-PGAMA copolymer exhibits efficient singlet oxygen generation (0.17) and indicates high fluorescence quantum yields (0.20). Notably, with UV-vis investigation, SPPLA-b-PLAMA showed a very specific recognition with RCA120 lectin. This will not only provide potentially prophyrin-cored star-shaped SPPLA-b-PLAMA block copolymers for targeted photodynamic therapy, but also improve the physical, biodegradation, biocompatibility properties of PLA-based biomaterials. PMID- 25138063 TI - High- but not low-intensity light leads to oxidative stress and quality loss of cold-stored baby leaf spinach. AB - BACKGROUND: Quality management in the fresh produce industry is an important issue. Spinach is exposed to various adverse conditions (temperature, light, etc.) within the supply chain. The present experiments were conducted to investigate the effect of light conditions (dark, low-intensity light (LL) and high-intensity light (HL)) and photoperiod (6 h HL and 18 h dark) on the quality changes of cold-stored spinach. RESULTS: HL exposure resulted in oxidative stress, causing tissue damage and quality loss as evidenced by increased membrane damage and water loss. The content of total ascorbic acid was reduced under HL conditions. On the other hand, storage of spinach under LL conditions gave promising results, as nutritional quality was not reduced, while texture maintenance was improved. No significant differences, with the exception of nutritional quality, were found between spinach leaves stored under continuous (24 h) low-intensity light (30-35 umol m(-2) s(-1)) and their counterparts stored under the same light integral over 6 h (130-140 umol m(-2) s(-1)). CONCLUSION: LL extended the shelf-life of spinach. The amount of light received by the leaves was the key factor affecting produce quality. Light intensity, however, has to be low enough not to cause excess oxidative stress and lead to accelerated senescence. PMID- 25138064 TI - Effect of almond consumption on the serum fatty acid profile: a dose-response study. AB - Consumption of almonds has been shown to be associated with a decreased risk of CHD, which may be related to their fatty acid (FA) composition. However, the effect of almond consumption on the serum FA composition is not known. Therefore, in the present study, we investigated whether almond consumption would alter the serum FA profile and risk of CHD, as calculated using Framingham's 10-year risk score, in a dose-dependent manner in hyperlipidaemic individuals when compared with a higher-carbohydrate control group using dietary interventions incorporating almonds. A total of twenty-seven hyperlipidaemic individuals consumed three isoenergetic (mean 1770 kJ/d) supplements during three 1-month dietary phases: (1) full-dose almonds (50-100 g/d); (2) half-dose almonds with half-dose muffins; (3) full-dose muffins. Fasting blood samples were obtained at weeks 0 and 4 for the determination of FA concentrations. Almond intake (g/d) was found to be inversely associated with the estimated Framingham 10-year CHD risk score (P= 0.026). In both the half-dose and full-dose almond groups, the proportions of oleic acid (OA) and MUFA in the TAG fraction (half-almond: OA P= 0.003; MUFA P= 0.004; full-almond: OA P< 0.001; MUFA P< 0.001) and in the NEFA fraction (half-almond: OA P= 0.01; MUFA P= 0.04; full-almond: OA P= 0.12; MUFA P= 0.06) increased. The estimated Framingham 10-year CHD risk score was inversely associated with the percentage change of OA (P= 0.011) and MUFA (P= 0.016) content in the TAG fraction. The proportions of MUFA in the TAG and NEFA fractions were positively associated with changes in HDL-cholesterol concentrations. Similarly, the estimated Framingham 10-year CHD risk score was inversely associated with the percentage change of OA (P= 0.069) and MUFA content in the NEFA fraction (P= 0.009). In conclusion, the results of the present study indicate that almond consumption increases OA and MUFA content in serum TAG and NEFA fractions, which are inversely associated with CHD lipid risk factors and overall estimated 10-year CHD risk. PMID- 25138065 TI - CXCL13 as a new biomarker of systemic lupus erythematosus and lupus nephritis - from bench to bedside? AB - Different studies over the last decade have linked the B cell-attracting chemokine CXC ligand 13 (CXCL13) to the autoimmune disease systemic lupus erythematosus (SLE). A pathogenetic role of this chemokine for disease manifestation in SLE was described initially in mouse models for SLE. Mechanisms of CXCL13 actions were also identified in SLE patients. Moreover, various clinical studies have identified CXCL13 serum levels as a useful biomarker in patients with SLE of different ethnicities for disease activity. In addition, CXCL13 seems to be a promising marker for the diagnosis of lupus nephritis, one of the most severe complications of SLE. However, its exact place within the mechanisms that lead to SLE remains to be defined. Further research is needed to resolve more details of the pathomechanism and the signalling pathway of CXCL13 in SLE. Blocking CXCL13 or the signal pathways of CXCL13 is seen as a promising therapeutic approach for SLE and will be addressed in the near future. This review summarizes all papers that linked CXCL13 to SLE and highlights its importance in the pathogenesis and diagnosis of SLE. PMID- 25138066 TI - Hyalurosome gene regulation and dose-dependent restoration of skin atrophy by retinaldehyde and defined-size hyaluronate fragments in dermatoporosis. AB - BACKGROUND: Dermatoporosis is an emerging clinical condition caused by chronological skin aging, long-term sun exposure and chronic use of corticosteroids; however, genomic expression in dermatoporosis and the efficacy of different therapeutic approaches to prevent and treat dermatoporosis have not been investigated so far. OBJECTIVE: We examined the possible effect of topical retinaldehyde (RAL) and defined-size hyaluronate fragments (HAFi) on the expression of hyalurosome genes potentially involved in the pathogenesis of dermatoporosis. We also explored the effect of different concentrations of HAFi on skin thickness. METHODS: 13 persons were separated into a young control group (n = 8) and a dermatoporosis group (n = 5). Topical treatment of both groups with a combination of 0.05% RAL and 1 or 0.2% HAFi was applied on the forearm twice daily for 30 days. Forearm skin biopsies of both groups were performed before and after application. Hyalurosome genes CD44, heparin-binding epidermal growth factor (HB-EGF), ErbB1, hyaluronate synthase 3 (HAS3) and Hyal2 were chosen as potential markers of dermatoporosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for quantification of mRNA expression of the target hyalurosome genes. Measurement of forearm skin thickness before and after treatment was performed by ultrasonography. Analysis of the results was done by Student's t test. A p value <0.05 was considered statistically significant. RESULTS: In qRT-PCR analysis the relative expression of hyalurosome (CD44, HAS3, HB-EGF) genes was found to be reduced in patients prior to topical treatment and to be notably increased following treatment. The reduced expression of CD44 and HAS3 in patients was specifically restored in dermatoporotic patients after treatment. No difference in skin thickness was observed in controls after treatment. The treatment caused a significant increase in skin thickness in dermatoporotic patients. This increase was more significant with 1% HAFi when compared to 0.2% HAFi. RAL and HAFi also caused a significant reduction in purpuric lesions in patients with dermatoporosis. CONCLUSION: Our results indicate that topically applied RAL and HAFi regulate hyalurosome gene expression in dermatoporosis and that they show a dose-dependent effect on the correction of skin atrophy in dermatoporotic patients. PMID- 25138067 TI - Differential accumulation of callose, arabinoxylan and cellulose in nonpenetrated versus penetrated papillae on leaves of barley infected with Blumeria graminis f. sp. hordei. AB - In plants, cell walls are one of the first lines of defence for protecting cells from successful invasion by fungal pathogens and are a major factor in basal host resistance. For the plant cell to block penetration attempts, it must adapt its cell wall to withstand the physical and chemical forces applied by the fungus. Papillae that have been effective in preventing penetration by pathogens are traditionally believed to contain callose as the main polysaccharide component. Here, we have re-examined the composition of papillae of barley (Hordeum vulgare) attacked by the powdery mildew fungus Blumeria graminis f. sp. hordei (Bgh) using a range of antibodies and carbohydrate-binding modules that are targeted to cell wall polysaccharides. The data show that barley papillae induced during infection with Bgh contain, in addition to callose, significant concentrations of cellulose and arabinoxylan. Higher concentrations of callose, arabinoxylan and cellulose are found in effective papillae, compared with ineffective papillae. The papillae have a layered structure, with the inner core consisting of callose and arabinoxylan and the outer layer containing arabinoxylan and cellulose. The association of arabinoxylan and cellulose with penetration resistance suggests new targets for the improvement of papilla composition and enhanced disease resistance. PMID- 25138069 TI - Genetic analysis of Enterobius vermicularis isolated from a chimpanzee with lethal hemorrhagic colitis and pathology of the associated lesions. AB - Human pinworms, Enterobius vermicularis, are normally recognized as minor pathogens. However, a fatal case of human pinworm infection has been reported in a nonhuman primate, a zoo reared chimpanzee. Here, we histopathologically examined the lesions in tissues from the deceased chimpanzee and genetically characterized the isolated worms to investigate the pathogenicity and determine the phylogeny. We identified ulcers deep in the submucosa where many parasites were found to have invaded the lamina propria mucosa or submucous tissue. An inflammatory reaction consisting mainly of neutrophils and lymphocytes but not eosinophils was observed around the parasites, and intense hemorrhage in the lamina propria was confirmed. The parasites were morphologically similar to E. vermicularis based on the shape of the copulatory spicules. Mitochondrial cytochrome c oxidase subunit 1 gene products were amplified from worm DNA by PCR and were genetically identified as E. vermicularis based on >98.7% similarity of partial sequences. Phylogenetic analysis revealed that the sequences clustered together with other chimpanzee E. vermicularis isolates in a group which has been referred to as type C and which differs from human isolates (type A). The samples were negative for bacterial pathogens and Entamoeba histolytica indicating that E. vermicularis could be pathogenic in chimpanzees. Phylogenetic clustering of the isolates indicated that the parasite may be host specific. PMID- 25138070 TI - Exsheathment and midgut invasion of nocturnally subperiodic Brugia malayi microfilariae in a refractory vector, Aedes aegypti (Thailand strain). AB - Exsheathment and midgut invasion of nocturnally subperiodic Brugia malayi microfilariae were analyzed using light and scanning electron microscopy in a refractory vector, Aedes aegypti (Thailand strain). Results showed that exsheathed microfilariae represented only approximately 1% of the total microfilaria midguts dissected at 5-min post-infected blood meal (PIBM). The percentage of exsheathed microfilariae found in midguts progressively increased to about 20, 60, 80, 90, and 100% at 1-, 2-5-, 6-12-, 18-36-, and 48-h PIBM, respectively. Importantly, all the microfilariae penetrating the mosquito midguts were exsheathed. Midgut invasion by the exsheathed microfilariae was observed between 2- and 48-h PIBM. SEM analysis revealed sheathed microfilariae surrounded by small particles and maceration of the microfilarial sheath in the midguts, suggesting that the midguts of the refractory mosquitoes might have protein(s) and/or enzyme(s) and/or factor(s) that induce and/or accelerate exsheathment. The microfilariae penetrated the internal face of the peritrophic matrix (PM) by their anterior part and then the midgut epithelium, before entering the hemocoel suggesting that PM was not a barrier against the microfilariae migrating towards the midgut. Melanized microfilariae were discovered in the hemocoel examined at 96-h PIBM suggesting that the refractory mosquitoes used melanization reactions against this parasite. This study provided evidence that A. aegypti (Thailand strain) has refractory mechanisms against B. malayi in both midgut and hemocoel. PMID- 25138071 TI - Outcomes of repeat laparoscopic liver resection compared to the primary resection. AB - BACKGROUND: Repeat laparoscopic liver resection (R-LLR) can be technically challenging. Data on this topic are scarce and many investigators would question its feasibility and outcomes. The aim of the present study was to evaluate the safety, feasibility, oncological efficiency and outcomes of R-LLR. METHODS: We reviewed a prospectively collected database of 403 patients undergoing 422 laparoscopic liver resections (LLRs) from August 2003 to August 2013. Data of 19 patients undergoing R-LLR were analyzed and compared to the primary resection (P LLR) in these patients. Demographic and clinical data were studied. A subgroup analysis was done for minor resections. RESULTS: Twenty R-LLRs were performed in 19 patients (female 58 %; mean age: 57.5 years; age range: 23-79 years). Colorectal liver metastases (CRLM) were the commonest indication for R-LLR (60 %), followed by neuroendocrine tumor liver metastases (NETLM) (20 %) and hepatocellular carcinoma (HCC) (10 %). The majority (90 %) of resections were for malignant disease (18/20). There were three conversions (15 %), and two patients developed complications (10 %). The operative time (p = 0.005) and blood loss (p = 0.03) were both significantly greater in R-LLR compared to P-LLR, whereas length of stay (median 4 days; p = 0.30) and complications (p = 0.58) did not differ between the groups. R0 resection rates for P-LLR and R-LLR were 95 and 90 %, respectively (p = 0.73). CONCLUSIONS: Repeat LLR is safe, feasible, and can be performed with minimal morbidity. It appears to be technically more challenging than P-LLR, but without any increase in complications or length of hospital stay. PMID- 25138068 TI - Identification, immunolocalization, and characterization analyses of an exopeptidase of papain superfamily, (cathepsin C) from Clonorchis sinensis. AB - Cathepsin C is an important exopeptidase of papain superfamily and plays a number of great important roles during the parasitic life cycle. The amino acid sequence of cathepsin C from Clonorchis sinensis (C. sinensis) showed 54, 53, and 49% identities to that of Schistosoma japonicum, Schistosoma mansoni, and Homo sapiens, respectively. Phylogenetic analysis utilizing the sequences of papain superfamily of C. sinensis demonstrated that cathepsin C and cathepsin Bs came from a common ancestry. Cathepsin C of C. sinensis (Cscathepsin C) was identified as an excretory/secretory product by Western blot analysis. The results of transcriptional level and translational level of Cscathepsin C at metacercaria stage were higher than that at adult worms. Immunolocalization analysis indicated that Cscathepsin C was specifically distributed in the suckers (oral sucker and ventral sucker), eggs, vitellarium, intestines, and testis of adult worms. In the metacercaria, it was mainly detected on the cyst wall and excretory bladder. Combining with the results mentioned above, it implies that Cscathepsin C may be an essential proteolytic enzyme for proteins digestion of hosts, nutrition assimilation, and immune invasion of C. sinensis. Furthermore, it may be a potential diagnostic antigen and drug target against C. sinensis infection. PMID- 25138074 TI - Inhibitory effect of plantaricin peptides (Pln E/F and J/K) against Escherichia coli. AB - Plantaricins are small bioactive peptides produced by Lactobacillus plantarum strains that exhibit significant antimicrobial activity against closely-related Gram-positive bacteria, including food spoilage organisms. In comparison, bacteriocins including plantaricins, are usually less effective against Gram negative organisms. In this study, we demonstrate that heterologously expressed and purified plantaricins, Pln E, -F, -J, and -K when tested against Gram negative model organism Escherichia coli K-12 were highly effective under certain conditions. The apparent tolerance of Gram-negative members to these peptides has been explained on the basis of the presence of the outer membrane (OM) that acts as a protective barrier. We have shown that agents and/or conditions that destabilize OM of E. coli K-12, make it susceptible to plantaricin peptides. In order to further strengthen this conclusion, an OM lipoprotein-defective lpp mutant strain of E. coli K-12 was also studied and compared. A significant loss of cell viability both in terms of CFU/ml as well as with live-dead dual staining combined with flow cytometry, could be demonstrated with the lpp mutant in comparison to the wild type strain. The results indicate that plantaricins can inhibit Gram-negative bacteria if the outer-membrane is weakened and it can be used in preservation of food with the help of some food-grade chelating agents. PMID- 25138075 TI - A longitudinal study on the impact of active surveillance for prostate cancer on anxiety and distress levels. AB - OBJECTIVE: Patients with potentially indolent prostate cancer (PC) can be managed with active surveillance (AS). Our objective was to analyse how anxiety and distress develop in men with untreated PC and whether highly anxious men quit AS. METHODS: One hundred and fifty Dutch patients who opted for AS in the Prostate cancer Research International: Active Surveillance Study were invited to participate in an additional prospective, longitudinal quality of life (QoL) study within 6 months after diagnosis. Participants completed questionnaires with validated measures on anxiety and distress at inclusion (t = 0), 9 (t = 9) and 18 (t = 18) months after diagnosis. We assessed changes in scores on depression (Center for Epidemiologic Studies Depression (CES-D) scale), generic anxiety (State-Trait Anxiety Inventory (STAI-6)), PC-specific anxiety (Memorial Anxiety Scale for Prostate Cancer (MAX-PC)) and decisional conflict (Decisional Conflict Scale (DCS)) about patients' treatment choice between t = 0, t = 9 and t = 18 using repeated measures analysis. RESULTS: Response rates for patients still on AS at t = 0, t = 9 and t = 18 assessments were 86%, 90% and 96%, respectively. Nine patients (7%, 9/129) between t = 0 and t = 9 and 33 of 108 patients (31%) between t = 9 and t = 18 stopped AS, mostly (86%) because of protocol-based reasons. CES-D, total MAX-PC and DCS scores did not change significantly (p > 0.05) when comparing t = 18 with t = 9 and t = 0 scores, but generic anxiety (STAI-6; p = 0.033) and fear of disease progression (sub-score of the MAX-PC; p = 0.007) decreased significantly. These differences, however, were clinically modest (0.089 SD and 0.281 SD). Overall, six of 129 men (5%) discontinued AS because of anxiety and distress. CONCLUSIONS: When men with low-risk PC are managed with AS, fear of disease progression and general anxiety decreased, and only few may discontinue AS because of anxiety and distress. This suggests that negative QoL effects are limited in men with favourable clinical characteristics who opted for AS. (Registered trial number, NTR1718) . PMID- 25138076 TI - Proteomic investigation of the hippocampus in prenatally stressed mice implicates changes in membrane trafficking, cytoskeletal, and metabolic function. AB - Prenatal stress influences the development of the fetal brain and so contributes to the risk of the development of psychiatric disorders in later life. The hippocampus is particularly sensitive to prenatal stress, and robust abnormalities have been described in the hippocampus in schizophrenia and depression. The aim of this study was to determine whether prenatal stress is associated with distinct patterns of differential protein expression in the hippocampus using a validated mouse model. We therefore performed a comparative proteomic study assessing female hippocampal samples from 8 prenatally stressed mice and 8 control mice. Differential protein expression was assessed using 2 dimensional difference in gel electrophoresis and subsequent mass spectrometry. The observed changes in a selected group of differentially expressed proteins were confirmed by Western blotting. In comparison to controls, 47 protein spots (38 individual proteins) were found to be differentially expressed in the hippocampus of prenatally stressed mice. Functional grouping of these proteins revealed that prenatal stress influenced the expression of proteins involved in brain development, cytoskeletal composition, stress response, and energy metabolism. Western blotting was utilized to validate the changes in calretinin, hippocalcin, profilin-1 and the signal-transducing adaptor molecule STAM1. Septin 5 could not be validated via Western blotting due to methodological issues. Closer investigation of the validated proteins also pointed to an interesting role for membrane trafficking deficits mediated by prenatal stress. Our findings demonstrate that prenatal stress leads to altered hippocampal protein expression, implicating numerous molecular pathways that may provide new targets for psychotropic drug development. PMID- 25138077 TI - Diffraction interference induced superfocusing in nonlinear Talbot effect. AB - We report a simple, novel subdiffraction method, i.e. diffraction interference induced superfocusing in second-harmonic (SH) Talbot effect, to achieve focusing size of less than lambdaSH/4 (or lambdapump/8) without involving evanescent waves or subwavelength apertures. By tailoring point spread functions with Fresnel diffraction interference, we observe periodic SH subdiffracted spots over a hundred of micrometers away from the sample. Our demonstration is the first experimental realization of the Toraldo di Francia's proposal pioneered 62 years ago for superresolution imaging. PMID- 25138078 TI - Use of prophylactic postoperative antibiotics during surgical drain presence following mastectomy. AB - BACKGROUND: National guidelines recommend one dose of perioperative antibiotics for breast surgery and discourage postoperative continuation. However, reported skin and soft tissue infection (SSI) rates after mastectomy range from 1-26 %, higher than expected for clean cases. Utility of routine or selective postoperative antibiotic use for duration of drain presence following mastectomy remains uncertain. METHODS: This study included all female patients who underwent mastectomy without reconstruction at our institution between 2005 and 2012. SSI was defined using CDC criteria or clinical diagnosis of cellulitis. Information on risk factors for infection (age, body mass index [BMI], smoking status, diabetes, steroid use), prior breast cancer treatment, drain duration, and antibiotic use was abstracted from medical records. Multivariable logistic regression was used to assess the association between postoperative antibiotic use and the occurrence of SSI, adjusting for concurrent risk factors. RESULTS: Among 480 patients undergoing mastectomy without reconstruction, 425 had sufficient documentation for analysis. Of these, 268 were prescribed antibiotics (63 %) at hospital discharge. An overall SSI rate of 7.3 % was observed, with 14 % of patients without postoperative antibiotics developing SSI compared with 3.4 % with antibiotics (p < 0.0001). Factors independently associated with SSI were smoking and advancing age. Diabetes, steroid use, BMI, prior breast surgery, neoadjuvant chemotherapy, prior radiation, concomitant axillary surgery, and drain duration were not associated with increased SSI rates. CONCLUSIONS: SSI rates among patients who did and did not receive postoperative antibiotics after mastectomy were significantly different, particularly among smokers and women of advanced age. These patient subgroups may warrant special consideration for postoperative antibiotics. PMID- 25138079 TI - Intraoperative radiation therapy: a critical analysis of the ELIOT and TARGIT trials. Part 2--TARGIT. AB - BACKGROUND: Two randomized intraoperative radiation therapy trials for early stage breast cancer were recently published. The ELIOT Trial used electrons (IOERT), and the TARGIT-A Trial Update used 50-kV X-rays (IORT). These studies were compared for similarities and differences. The results were analyzed and used to determine which patients might be suitable for single-dose treatment. METHODS: The primary sources of data were the ELIOT Trial and TARGIT-A Trial, as well as a comprehensive analysis of the peer-reviewed literature of accelerated partial breast irradiation (APBI) using 50-kV X-rays or electrons. Studies published or presented prior to March 2014 were analyzed for efficacy, patient restrictions, complications, and outcome. RESULTS: With a median follow-up of 5.8 years, the 5-year recurrence rates for ELIOT versus EBRT patients were 4.4 and 0.4 %, respectively, p = 0.0001. A low-risk ELIOT group was identified with a 5 year recurrence rate of 1.5 %. With a median follow-up of 29 months, the 5-year recurrence rates for the TARGIT-A versus EBRT patients were 3.3 and 1.3 %, respectively, p = 0.042. CONCLUSIONS: With 5.8 years of median follow-up, IOERT appears to have a subset of low risk women for whom IOERT is acceptable. With 29 months of median follow-up the results of IORT with 50-kV devices are promising, but longer follow-up data are required. At the current time, single-fraction IOERT or IORT patients should be treated under strict institutional protocols. PMID- 25138080 TI - Exploring barriers to payer utilization of genetic counselors. AB - Access to genetic counselors' services is neither universal nor automatic, due in part to the gatekeeper role of healthcare payers--the companies and agencies that purchase healthcare services on patients' behalf and control the bulk of healthcare spending. This pilot study surveyed and analyzed the relative importance of barriers to expanded payer coverage of genetic counselors' services. Surveys were mailed to 263 medical directors and quality assurance directors at health insurance carriers throughout the United States. Respondents provided demographic information and indicated the importance of nine possible barriers, plus an optional write-in "other." Twenty-two surveys were analyzed. "Evidence that use of genetic counselors improves health outcomes" led the list of factors having a significant/very significant influence on coverage policy. Sixteen respondents (73 %) rated this factor "4" or "5" on a Likert scale; it also received the most #1 rankings and the highest score using a weighted-mean analysis. Provider practice guidelines, CMS/Medicare regulations, and genetic counselor licensure-all of which are outside of payers' direct control-also ranked highly. The research demonstrates that although the potential barriers to expanded reimbursement for genetic counselors are numerous and complex, some are more consistently identified as important and therefore more deserving of legislative and advocacy resources to effect change. Future research should endeavor to increase survey response and include providers as well as payers. PMID- 25138081 TI - The utilization of counseling skills by the laboratory genetic counselor. AB - The number of available genetic testing options and the nuances associated with these options continue to expand. In addition, the scope of genetic testing has broadened to areas and specialties beyond Medical Genetics. In response to these changes, diagnostic laboratories have employed genetic counselors to help navigate the increasing complexity of genetic testing, given their expertise and training in human genetics. However a largely unrecognized aspect of this role involves the use of counseling skills. Counseling skills are used by laboratory genetic counselors in a variety of situations to convey information and facilitate understanding among clinicians and medical staff. This helps to reduce test ordering errors, promote optimal test utilization, and ensure best patient care practices. The specific counseling skills used by laboratory counselors will be explored using three fictional case vignettes, followed by a discussion of the applicability of these skills in other contexts. Exploration of the unique ways in which laboratory genetic counselors apply their counseling skills can be useful for professional development and instructive for graduate training programs. PMID- 25138083 TI - The clash of mechanical and electrical size-effects in ZnO nanowires and a double power law approach to elastic strain engineering of piezoelectric and piezotronic devices. AB - The piezoelectric performance of ultra-strength ZnO nanowires (NWs) depends on the subtle interplay between electrical and mechanical size-effects. "Size dependent" modeling of compressed NWs illustrates why experimentally observed mechanical stiffening can indeed collide with electrical size-effects when the size shrinks, thereby lowering the actual piezoelectric function from bulk estimates. "Smaller" is not necessarily "better" in nanotechnology. PMID- 25138082 TI - Chiral amine synthesis using omega-transaminases: an amine donor that displaces equilibria and enables high-throughput screening. AB - The widespread application of omega-transaminases as biocatalysts for chiral amine synthesis has been hampered by fundamental challenges, including unfavorable equilibrium positions and product inhibition. Herein, an efficient process that allows reactions to proceed in high conversion in the absence of by product removal using only one equivalent of a diamine donor (ortho xylylenediamine) is reported. This operationally simple method is compatible with the most widely used (R)- and (S)-selective omega-TAs and is particularly suitable for the conversion of substrates with unfavorable equilibrium positions (e.g., 1-indanone). Significantly, spontaneous polymerization of the isoindole by product generates colored derivatives, providing a high-throughput screening platform to identify desired omega-TA activity. PMID- 25138084 TI - The development of ataxia telangiectasia mutated kinase inhibitors. AB - Radiation and genotoxic drugs are two of the cornerstones of current cancer treatment strategy. However, this type of therapy often suffers from radio- or chemo-resistance caused by DNA repair mechanisms. With the aim of increasing the efficacy of these treatments, there has been great interest in studying DNA damage responses (DDR). Among the plethora of signal and effector proteins involved in DDR, three related kinases ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related) and DNA-PK (DNA-dependent protein kinase) play the main roles in initiation and regulation of signaling pathways in response to DNA double and single strand breaks (DSB and SSB). ATM inhibitors, as well as those of ATR and DNA-PK, provide an opportunity to sensitize cancer cells to therapy. Moreover, they can lead to selective killing of cancer cells, exploiting a concept known as synthetic lethality. However, only a very few selective inhibitors have been identified to this date. This mini-review is focused both on the development of selective inhibitors of ATM and other inhibitors which have ATM as one of their targets. PMID- 25138085 TI - Xanthomicrol: a comprehensive review of its chemistry, distribution, biosynthesis and pharmacological activity. AB - Highly methoxylated flavones, which have known potential as cancer chemopreventive agents, accumulate on the leaf surfaces of some plant species and their physiological role is to protect the plant against harmful UV radiation. Xanthomicrol is one of the methoxylated flavones currently attracting most attention from researchers worldwide because of its promising pharmacological activities, including anti-spasmodic, anti-platelet and anti-cancer effects, among others. This review covers the chemistry and biological origin, distribution and pharmacological activity of xanthomicrol. Knowledge of the botanical distribution of this compound will not only encourage the use of plant sources for pharmacological purposes, but will also serve as a reference in the search for this valuable flavonoid in another genus or family. New approaches to xanthomicrol production are also described, including biotechnological attempts to develop xanthomicrol-producing plant cell factories. PMID- 25138086 TI - The toolbox of designing nanoparticles for tumors. AB - Nanoparticles (NPs) show great promise in the treatment of a wide range of diseases, which provides advantages and offers a new prospect for tumor detection, prevention and treatment. In order to eradicate the cancer cell, the NPs need to flow to different regions of tumors via blood vessels, and then penetrate through the interstitial space to reach the target cells. However, the environment and physiological characteristics in tumor tissues are different from that in normal ones, mainly in the irregular blood vessels, the lack of lymphatic network, low pH, hypoxia, immune function and so on. Meanwhile, the differences also exist among different tumor tissues. To achieve the optimal therapeutic effect, the NPs should be carefully designed by considering the therapeutic application, the target site and the route of administration. This review shows a variety of barriers in the tumor tissues, and provides a toolbox of designing the NPs for tumor treatment. In particular, the particle size, shape and surface chemistry, and the NPs in preclinical and clinical stage use have been discussed. PMID- 25138087 TI - Sea, carbohydrates and clotting: a triad on the road of drug discovery. AB - Cardiovascular diseases (CDs) are the principal cause of death in the world. Anticoagulation is the commonest therapeutic strategy for treatments of CDs in clinical settings. Although possessed of numerous downsides, heparin is the main clinical anticoagulant/antithrombotic agent used so far. Novel sulfated polysaccharides like the marine dermatan sulfate, sulfated fucans and galactans are also able to block clot and thrombus formation. These relatively new marine glycans call special attention mostly due to their unique structures and distinct mechanisms of action. This structural uniqueness is seen by the peculiar aspect of these polysaccharides being made of clear and regular sulfation patterns. The structures have been reported only in polysaccharides from marine invertebrates like sea urchins and cucumbers. This report intends to prove the promising combination of the triad sea-carbohydrates-clotting in drug discovery of the cardiovascular field. PMID- 25138088 TI - Benzimidazoles: an ideal privileged drug scaffold for the design of multitargeted anti-inflammatory ligands. AB - The recent research area endeavors to discover ultimate multi-target ligands, an increasingly feasible and attractive alternative to existing mono-targeted drugs for treatment of complex, multi-factorial inflammation process which underlays plethora of debilitated health conditions. In order to improvise this option, exploration of relevant chemical core scaffold will be an utmost need. Privileged benzimidazole scaffold being historically versatile structural motif could offer a viable starting point in the search for novel multi-target ligands against multi-factorial inflammation process since, when appropriately substituted, it can selectively modulate diverse receptors, pathways and enzymes associated with the pathogenesis of inflammation. Despite this remarkable capability, the multi target capacity of the benzimidazole scaffold remains largely unexploited. With this in focus, the present review article attempts to provide synopsis of published research to exemplify the valuable use of benzimidazole nucleus and focus on their suitability as starting scaffold to develop multi-targeted anti inflammatory ligands. PMID- 25138089 TI - Drug targeting systems for cancer therapy: nanotechnological approach. AB - Progress in cancer treatment remains challenging because of the great nature of tumor cells to be drug resistant. However, advances in the field of nanotechnology have enabled the delivery of drugs for cancer treatment by passively and actively targeting to tumor cells with nanoparticles. Dramatic improvements in nanotherapeutics, as applied to cancer, have rapidly accelerated clinical investigations. In this review, drug-targeting systems using nanotechnology and approved and clinically investigated nanoparticles for cancer therapy are discussed. In addition, the rationale for a nanotechnological approach to cancer therapy is emphasized because of its promising advances in the treatment of cancer patients. PMID- 25138090 TI - An overview of conjugated linoleic acid: microbial production and application. AB - Conjugated linoleic acid (CLA) has attracted considerable attention in health due to its important physiological properties proved in several in vivo experiments. Many bacteria, especially some probiotics, are able to produce CLA from the linoleic acid (LA) present in milk. In this review, CLA production by microorganisms is described. Then factors on the influencing the microbial production and the initial CLA content in milk fat are introduced. After a glimpse on the content of CLA in dairy products and human body, health benefits of CLA including anti-cancer, anti-diabetic, antiathrosclerosis and anti osteoporosis properties, as well as prevention of body fat increase and function as stimulator of the immunity system are explained. PMID- 25138091 TI - Natural products; pharmacological importance of family Cucurbitaceae: a brief review. AB - Compounds derived from nature have played a major role in drug discovery. They became the basis for the development of new pharmaceuticals. In this scope, family Cucurbitaceae is a prominent source of secondary metabolites, mainly triterpenoids. In this paper, we provide a brief review of cucurbitane metabolites that exhibit an extensive range of biological actions specifically antidiabetic, anti-inflammatory, cytotoxic, hepatoprotective, and antiparasitic effects. PMID- 25138092 TI - Enoyl ACP reductase as effective target for the synthesized novel antitubercular drugs: a-state-of-the-art. AB - The emergence of drug resistant strains of important human pathogens has created an urgent necessity to find new targets and novel antitubercular agents. According to the literature survey, we noticed that enoyl ACP reductase is one of the most promising targets. This enzyme is the most important catalyst for the FAS II synthesis of mycolic acid, which is the most essential component of the mycobacterial cell wall. This review summarizes the progress made in the design of enoyl ACP reductase inhibitors and the role played by 3D-structure of the enzyme in drug design process. PMID- 25138093 TI - Occurrence and biological activities of eremophilane-type sesquiterpenes. AB - As important members of the terpenes family, sesquiterpenes represent a group of natural compounds with diverse skeletal types. Among them, the eremophilane-type sesquiterpenes, widely present in several genera (such as Ligularia, Senecio, Cacalia) of Asteraceae, account for a small number of natural compounds and form differently from other sesquiterpenes because they challenged the isoprene rule of biosynthesis. Due to the unique structural features and various functional groups, these compounds possess a number of biological activities such as anti tumor, anti-bacterial and anti-inflammatory, having received increasing interest in the recent years. This review summarizes the occurrence of eremophilane-type sesquiterpenes and research progresses on their biological activities since the 1990 s. PMID- 25138094 TI - Combined cancer therapy with non-conventional drugs: all roads lead to AMPK. AB - AMP-activated protein kinase (AMPK) is a key energy sensor that regulates cellular energy homeostasis. AMPK activation is associated with decreased phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase and causes a general reduction in mRNA translation and protein synthesis. Therefore, AMPK is a novel target for anticancer therapy. Metformin and aspirin are two traditional drugs that are widely used as anti-diabetes and non-steroidal anti-inflammatory drugs (NSAIDs), respectively. Much evidence has confirmed that these two drugs demonstrated encouraging anti-cancer properties. Most importantly, both inhibited tumor proliferation and were mainly dependent on the AMPK/mTOR signaling pathway. In addition, several other drugs, such as resveratrol, berberine, statins, epigallocatechin gallate (EGCG) and capsaicin, have provided a similar capacity for tumor inhibition, and the anti-cancer effects of most of them were mainly the result of AMPK activation. In the current review, we summarize the literature on combination therapy based on these non-classical drugs and their potential mechanisms for activating AMPK. Combinations of these drugs will provide a novel cancer therapeutic regimen. PMID- 25138095 TI - Identification of a pathogenic variant in TREX1 in early-onset cerebral systemic lupus erythematosus by Whole-exome sequencing. AB - Objective. Systemic lupus erythematosus (SLE) isa chronic and heterogeneous autoimmune disease. Both twin and sibling studies indicate a strong genetic contribution to lupus, but in the majority of cases the pathogenic variant remains to be identified. The genetic contribution to disease is likely to be greatest in cases with early onset and severe phenotypes. Whole-exome sequencing now offers the possibility of identifying rare alleles responsible for disease in such cases. This study was undertaken to identify genetic causes of SLE using whole-exome sequencing.Methods. We performed whole-exome sequencing in a 4-year old girl with early-onset SLE and conducted biochemical analysis of the putative defect.Results. Whole-exome sequencing in a 4-year-old girl with cerebral lupus identified a rare, homozygous mutation in the three prime repair exonuclease 1 gene(TREX1) that was predicted to be highly deleterious.The TREX1 R97H mutant protein had a 20-fold reduction in exonuclease activity and was associated with an elevated interferon-alpha signature in the patient.The discovery and characterization of a pathogenic TREX1 variant in our proband has therapeutic implications.The patient is now a candidate for therapy. Conclusion. Our study is the first to demonstrate that whole-exome sequencing can be used to identify rare or novel deleterious variants as genetic causes of SLE and, through a personalized approach, improve therapeutic options. PMID- 25138096 TI - Dr. Richard Fitzpatrick July 21, 1944-July 12, 2014. PMID- 25138097 TI - An automatic robotic system for three-dimensional tooth crown preparation using a picosecond laser. AB - BACKGROUND: Laser techniques have been introduced into dentistry to overcome the drawbacks of traditional treatment methods. The existing methods in dental clinical operations for tooth crown preparation have several drawbacks which affect the long-term success of the dental treatment. OBJECTIVE: To develop an improved robotic system to manipulate the laser beam to achieve safe and accurate three-dimensional (3D) tooth ablation, and thus to realize automatic tooth crown preparation in clinical operations. METHOD: We present an automatic laser ablation system for tooth crown preparation in dental restorative operations. The system, combining robotics and laser technology, is developed to control the laser focus in three-dimensional motion aiming for high speed and accuracy crown preparation. The system consists of an end-effector, a real-time monitor and a tooth fixture. A layer-by-layer ablation method is developed to control the laser focus during the crown preparation. Experiments are carried out with picosecond laser on wax resin and teeth. RESULTS: The accuracy of the system is satisfying, achieving the average linear errors of 0.06 mm for wax resin and 0.05 mm for dentin. The angle errors are 4.33 degrees for wax resin and 0.5 degrees for dentin. The depth errors for wax resin and dentin are both within 0.1 mm. The ablation time is 1.5 hours for wax resin and 3.5 hours for dentin. CONCLUSIONS: The ablation experimental results show that the movement range and the resolution of the robotic system can meet the requirements of typical dental operations for tooth crown preparation. Also, the errors of tooth shape and preparation angle are able to satisfy the requirements of clinical crown preparation. Although the experimental results illustrate the potential of using picosecond lasers for 3D tooth crown preparation, many research issues still need to be studied before the system can be applied to clinical operations. PMID- 25138099 TI - Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome. AB - Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child-parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5 containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID. PMID- 25138101 TI - Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an unselected early breast cancer population. AB - In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast cancer patients, unselected for family history, diagnosed in a cancer hospital before the age of 50 years in 1974-2002; most prevalent Dutch pathogenic BRCA1/2 mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%) of the patients were proven to be BRCA1/2 mutation carriers. We found that 78% and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for referral to the CGC based on age, family history and synchronous multiple tumors; reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor. The highest AUC was obtained by shifting the age at diagnosis threshold criterion from 40 to 35 years and by adding a 'triple-negative breast cancer' criterion with an age threshold of 45 years; the specificity increased to 71.2%, whereas the sensitivity remained the same; that is, a referral of fewer patients will lead to the identification of at least the same number of BRCA1/2 mutation carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research setting had been referred for counseling and testing. Our results indicate that, awaiting a possibly more extended mutation screening of all breast cancer patients, the triple-negative status of a breast cancer should be added to the CGC referral criteria. PMID- 25138100 TI - Identification of a novel ARL13B variant in a Joubert syndrome-affected patient with retinal impairment and obesity. AB - Joubert syndrome (JS) is a genetically heterogeneous autosomal recessive ciliopathy with 22 genes implicated to date, including a small, ciliary GTPase, ARL13B. ARL13B is required for cilia formation in vertebrates. JS patients display multiple symptoms characterized by ataxia due to the cerebellar vermis hypoplasia, and that can also include ocular abnormalities, renal cysts, liver fibrosis or polydactyly. These symptoms are shared with other ciliopathies, some of which display additional phenotypes, such as obesity. Here we identified a novel homozygous missense variant in ARL13B/JBTS8 in a JS patient who displayed retinal defects and obesity. We demonstrate the variant disrupts ARL13B function, as its expression did not rescue the mutant phenotype either in Arl13b(scorpion) zebrafish or in Arl13b(hennin) mouse embryonic fibroblasts, while the wild-type ARL13B did. Finally, we show that ARL13B is localized within the primary cilia of neonatal mouse hypothalamic neurons consistent with the known link between hypothalamic ciliary function and obesity. Thus our data identify a novel ARL13B variant that causes JS and retinopathy and suggest an extension of the phenotypic spectrum of ARL13B mutations to obesity. PMID- 25138102 TI - A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine. AB - Hereditary sensorineural hearing loss is an extremely clinical and genetic heterogeneous disorder in humans. Especially, syndromic hearing loss is subdivided by combinations of various phenotypes, and each subtype is related to different genes. We present a new form of progressive hearing loss with migraine found to be associated with a variant in the ATP1A2 gene. The ATP1A2 gene has been reported as the major genetic cause of familial migraine by several previous studies. A Korean family presenting progressive hearing loss with migraine was ascertained. The affected members did not show any aura or other neurologic symptoms during migraine attacks, indicating on a novel phenotype of syndromic hearing loss. To identify the causative gene, linkage analysis and whole-exome sequencing were performed. A novel missense variant, c.571G>A (p.(Val191Met)), was identified in the ATP1A2 gene that showed co-segregation with the phenotype in the family. In silico studies suggest that this variant causes a change in hydrophobic interactions and thereby slightly destabilize the A-domain of Na(+)/K(+)-ATPase. However, functional studies failed to show any effect of the p.(Val191Met) substitution on the catalytic rate of this enzyme. We describe a new phenotype of progressive hearing loss with migraine associated with a variant in the ATP1A2 gene. This study suggests that a variant in Na(+)/K(+)-ATPase can be involved in both migraine and hearing loss. PMID- 25138103 TI - Orange alert. PMID- 25138105 TI - Misclassification due to age grouping in measures of child development. AB - PURPOSE: Screens for developmental delay generally provide a set of norms for different age groups. Development varies continuously with age, however, and applying a single criterion for an age range will inevitably produce misclassifications. In this report, we estimate the resulting error rate for one example: the cognitive subscale of the Bayley Scales of Infant and Toddler Development (BSID-III). DESIGN: Data come from a general population sample of 594 children (305 male) aged 1 month to 42.5 months who received the BSID-III as part of a validation study. We used regression models to estimate the mean and variance of the cognitive subscale as a function of age. We then used these results to generate a dataset of one million simulated participants and compared their status before and after division into age groups. Finally, we applied broader age bands used in two other instruments and explored likely validity limitations when different instruments are compared. RESULTS: When BSID-III age groups are used, 15% of cases are missed and 15% of apparent cases are false positives. Wider age groups produced error rates from 27% to 46%. Comparison of different age groups suggests that sensitivity in validation studies would be limited, under certain assumptions, to 70% or less. IMPLICATIONS: The use of age groups produces a large number of misclassifications. Although affected children will usually be close to the threshold, this may lead to misreferrals. Results may help to explain the poor measured agreement of development screens. Scoring methods that treat child age as continuous would improve instrument accuracy. PMID- 25138104 TI - Assessment of neonatal care in clinical training facilities in Kenya. AB - OBJECTIVE: An audit of neonatal care services provided by clinical training centres was undertaken to identify areas requiring improvement as part of wider efforts to improve newborn survival in Kenya. DESIGN: Cross-sectional study using indicators based on prior work in Kenya. Statistical analyses were descriptive with adjustment for clustering of data. SETTING: Neonatal units of 22 public hospitals. PATIENTS: Neonates aged <7 days. MAIN OUTCOME MEASURES: Quality of care was assessed in terms of availability of basic resources (principally equipment and drugs) and audit of case records for documentation of patient assessment and treatment at admission. RESULTS: All hospitals had oxygen, 19/22 had resuscitation and phototherapy equipment, but some key resources were missing for example kangaroo care was available in 14/22. Out of 1249 records, 56.9% (95% CI 36.2% to 77.6%) had a standard neonatal admission form. A median score of 0 out of 3 for symptoms of severe illness (IQR 0-3) and a median score of 6 out of 8 for signs of severe illness (IQR 4-7) were documented. Maternal HIV status was documented in 674/1249 (54%, 95% CI 41.9% to 66.1%) cases. Drug doses exceeded recommendations by >20% in prescriptions for penicillin (11.6%, 95% CI 3.4% to 32.8%) and gentamicin (18.5%, 95% CI 13.4% to 25%), respectively. CONCLUSIONS: Basic resources are generally available, but there are deficiencies in key areas. Poor documentation limits the use of routine data for quality improvement. Significant opportunities exist for improvement in service delivery and adherence to guidelines in hospitals providing professional training. PMID- 25138107 TI - A review of pre-admission advanced airway management in combat casualties, Helmand Province 2013. AB - OBJECTIVES: Airway compromise is the third leading cause of potentially preventable combat death. Pre-hospital airway management has lower success rates than in hospital. This study reviewed advanced airway management focusing on cricothyroidotomies and supraglottic airway devices in combat casualties prior to admission to a Role 3 Hospital in Afghanistan. METHODS: This was a retrospective review of all casualties who required advanced airway management prior to arrival at the Role 3 Hospital, Bastion, Helmand Province over a 30-week period identified by the US Joint Theatre Trauma Registry. The notes and relevant X-rays were analysed. The opinions of US and UK clinical Subject Matter Experts (SME) were then sought. RESULTS: Fifty-seven advanced airway interventions were identified. 45 casualties had attempted intubations, 37 (82%) were successful and of those who had failed intubations, one had a King LT Airway (supraglottic device) and seven had a rescue cricothyroidotomy. The other initial advanced airway interventions were five attempted King LT airways and seven attempted cricothyroidotomies. In total, 14 cricothyroidotomies were performed; in this group, there were nine complications/significant events. CONCLUSIONS: The SMEs suggested that dedicated surgical airway kits should be used and students in training should be taught to secure the cricothyroidotomy tube as well as how to insert it. This review re-emphasises the need to 'ensure the right person, with the right equipment and the right training, is present at the right time if we are to improve the survival of patients with airway compromise on the battlefield'. The audit reference number is RCDM/Res/Audit/1036/12/0368. PMID- 25138106 TI - Changes in sleep characteristics and airway obstruction in OSAHS patients with multi-level obstruction following simple UPPP, UPPP-GA, or UPPP-TBA: a prospective, single-center, parallel group study. AB - OBJECTIVE: To investigate changes in S3 sleep and the apnea hypopnea index (AHI), SpO2 desaturation and CT90, and to determine changes in the degree of airway collapse and in the cross-sectional area of the retropalatal and lingual region in obstructive sleep apnea hypopnea syndrome patients. METHOD: All subjects underwent overnight polysomnography and were evaluated using Muller's test and magnetic resonance imaging at baseline, 3, and 12 months following surgery. RESULT: The mean S3 scores in patients receiving uvulopalatopharyngoplasty combined with genioglossus advancement (UPPP-GA) or UPPP combined with tongue base advancement using the ReposeTM system (UPPP-TBA) noticeably increased. Marked improvement was seen in the mean AHI, LSO2, and CT90 scores 3 and 12 months following surgery compared to baseline. Airway collapsed by 25-50% in the greatest proportion undergoing surgery at the tongue base. CONCLUSION: UPPP-GA and UPPP-TBA more effectively improve S3 sleep, and mean AHI, LSO2, and CT90 scores. In addition, they effectively alleviate airway obstruction by improving the cross-sectional area of these regions. PMID- 25138108 TI - Cardiovascular disease and cancer compete for the outcome of death. PMID- 25138109 TI - Does a single session of high-intensity interval training provoke a transient elevated risk of falling in seniors and adults? AB - BACKGROUND: Balance and strength training can reduce seniors' fall risk up to 50%. Available evidence suggests that acute bouts of neuromuscular and endurance exercise deteriorate postural control. High-intensity endurance training has been successfully applied in different populations. Thus, it seemed valuable to examine the acute effects of high-intensity interval training (HIIT) on neuromuscular performance in seniors and young adults. OBJECTIVE: The acute impact of a HIIT session on balance performance and muscle activity after exercise cessation and during post-exercise recovery was examined in young and old adults. We intended to investigate whether a transient exercise-induced fall risk may occur in both groups. METHODS: 20 healthy seniors (age 70 (SD 4) years) and young adults (age 27 (SD 3) years) were examined on 3 days. After exhaustive ramp-like treadmill testing in order to determine maximal heart rate (HRmax) on the first day, either a 4 * 4 min HIIT at 90% of HRmax or a control condition (CON) was randomly performed on the second and third day, respectively. Balance performance (postural sway) was assessed during single limb stance with open eyes (SLEO) and double limb stance with closed eyes (DLEC). EMG was recorded for the soleus (SOL), anterior tibialis (TIB), gastrocnemius (GM) and peroneus longus (PL) muscles at the dominant leg. All measures were collected before, immediately as well as 10, 30 and 45 min after HIIT and CON, respectively. RESULTS: Compared to CON, HIIT induced significant increases of postural sway immediately after exercise cessation during SLEO in both groups (adults: p < 0.001, Delta = +25% sway; seniors: p = 0.007, Delta = +15% sway). Increased sway during DLEC was only found for seniors immediately and 10 min after HIIT (post: p = 0.003, Delta = +14% sway, 10 min post: p = 0.004, Delta = +18% sway). Muscle activity was increased during SLEO for TIB until 10 min post in seniors (0.008 < p < 0.03) and immediately after HIIT in adults (p < 0.001). CONCLUSION: HIIT training may cause an acute 'open-fall-window' with a transient impairment of balance performance for at least 10 min after exercise cessation in both groups. Occluded vision in seniors seems to prolong this period up to 30 min. Thus, the advantage of HIIT with regard to time efficiency seems debatable when considering transient HIIT induced impairments of neuromuscular function. PMID- 25138110 TI - Treatment of pegylated interferon-alpha2a in chronic hepatitis B patients demonstrating a spontaneous decline in HBV DNA after acute exacerbation. AB - BACKGROUND: Acute exacerbation (AE) in chronic hepatitis B (CHB) is usually followed by a spontaneous decline in HBV DNA levels. The subsequent treatment is controversial. In this study, we evaluated the efficacy and safety of pegylated interferon-alpha2a (PEG-IFN-alpha2a) for such CHB patients. METHODS: A total of 74 hepatitis B e antigen (HBeAg)-positive patients with a spontaneous HBV DNA decline (by >2 log10 IU*ml(-1), compared with baseline levels before antiviral treatment) after AE (alanine aminotransferase [ALT]: 10-30-fold the upper limit of normal [ULN], total bilirubin [TBIL]: 2-20 mg*dl(-1), prothrombin time activity >60%) were included. In total, 22 patients (group A) received PEG-IFN alpha2a treatment (180 ug*kg(-1)*week(-1), when ALT was <10 ULN and TBIL<2 mg*dl( 1)) for 48 weeks, with 48 weeks of treatment-free follow-up. Twenty-one patients (group B) selected continual entecavir therapy. Thirty-one patients (group C, control group) received routine liver-protective drugs. RESULTS: At week 96, virological response rates were 90.5%, 100% and 48%, and ALT normalization rates were 81%, 95% and 40% for groups A, B and C, respectively. HBeAg seroconversion rates were 71.4%, 45% and 32% in groups A, B and C, respectively. A high hepatitis B surface antigen (HBsAg) loss rate was observed in PEG-IFN-alpha2a treated patients, while no entecavir-treated patients achieved HBsAg loss. Group A patients suffered from typical PEG-IFN therapy-related adverse events. No severe adverse event was observed in any groups. CONCLUSIONS: PEG-IFN-alpha2a is effective and safe for treating CHB patients demonstrating a spontaneous decline in HBV DNA after AE, and yields an increased likelihood of HBsAg loss. PMID- 25138112 TI - Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy. AB - Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus. The Israeli Society of Medical Geneticists (ISMG) supports its use according to the guidelines stated herein. The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies. Because false-positive results may occur, an abnormal result must be validated by invasive prenatal testing. At this juncture, NIPT does not replace existing prenatal screening tests for Down syndrome, as these are relatively inexpensive and cost-effective. Nonetheless, NIPT may be offered to women considered to be at high risk for fetal chromosomal abnormalities as early as 10 weeks of gestation. The ISMG states that NIPT should be an informed patient choice, and that pretest counseling regarding the limitations of NIPT is warranted. Women at high risk for genetic disorders not detected by NIPT should be referred for genetic counseling. A normal test result may be conveyed by a relevant healthcare provider, while an abnormal result should be discussed during a formal genetic consultation session. PMID- 25138111 TI - Fear of movement/(Re)injury in low back pain: confirmatory validation of a German version of the Tampa Scale for Kinesiophobia. AB - BACKGROUND: The Tampa Scale for Kinesiophobia (TSK), an instrument for measuring fear of movement/(re)injury, has been confirmed as an important predictor for the persistence of pain-related disability. The aims of this study were to evaluate the psychometric properties of a German version of the TSK (TSK-GV), examining aspects of content validity with special focus on fear-avoidance and endurance, and to confirm criterion-related validity in patients with low back pain (LBP). METHODS: A total of 191 patients with LBP were included in this study. Several models with different factor structures from published studies were compared in a confirmatory factor analysis. Internal consistencies of the TSK-GV and its subscales were examined, and correlations with related self-report measures were calculated. RESULTS: The internal consistency of the TSK-GV was alpha = 0.73. A two-factor model with 11 items was found to be the best fit for our data. The two factors were labelled Somatic Focus (SF) and Activity Avoidance (AA). The total score, SF and AA revealed moderate to high correlations with other fear-avoidance variables. CONCLUSIONS: The TSK-GV is a reliable and valid measure for assessing the fear of movement/(re)injury. PMID- 25138113 TI - Ten years of experience with first-trimester screening for fetal aneuploidy employing biochemistry from gestational weeks 6+0 to 13+6. AB - OBJECTIVES: To validate the performance of first-trimester screening for fetal aneuploidy employing blood samples drawn in gestational weeks 6-13. METHODS: Prospective combined first-trimester screening for fetal aneuploidy in Denmark was validated in two large datasets: (1) a dataset from the Central Denmark Region including 147,768 pregnancies from October 2003 to October 2013, and (2) a national dataset including 220,739 pregnancies from January 2008 to August 2011. RESULTS: For trisomy 21, the weekly median multiple of the median (MoM) increased from 0.37 in week 6 to 0.70 in week 13 (pregnancy-associated plasma protein-A), and from 0.99 in week 6 to 2.68 in week 13 (free betahCG). The overall detection rate (DR) for fetal trisomy 21 was 91.2%. Employing blood samples from gestational week 9, the DR was 97% (p = 0.05). For fetal trisomy 18, trisomy 13 and triploidy, the overall DRs after first-trimester screening were 79.5, 86 and 85%. In the national dataset, the overall DR for trisomy 21 was 86.3% ranging from 89 (weeks 9 and 10) to 80% (weeks 12 and 13). CONCLUSION: The results from both datasets show that blood sampling in gestational weeks 9-10 is a robust and high-performance strategy, which can be applied for routine first-trimester screening in clinical practice. (c) 2014 S. Karger AG, Basel. PMID- 25138115 TI - Prospective study of spinal orthoses in women. AB - BACKGROUND: There are not many clinical trials investigating the efficiency and compliance of using spinal orthoses in the management of osteoporosis. OBJECTIVES: The purpose of this study was to investigate the effect of long-term use and the compliance of spinal orthoses in postmenopausal women with vertebral fractures. STUDY DESIGN: Clinical trial of spinal orthoses in postmenopausal women. METHODS: Women were separated into groups wearing different types of orthoses (Spinomed, Osteomed, Spinomed active, and Spine-X). Isometric maximum strength of trunk muscles (F/Wabdominals-extensors) was calculated and back pain was assessed in all women. In addition, women completed a compliance questionnaire about the use of the orthoses. RESULTS: Spinomed decreased pain (p = 0.001) and increased trunk muscle strength (F/Wabdominals, p = 0.005 and F/Wextensors, p = 0.003, respectively). The compliance of wearing an orthosis for 6 months was 66%. CONCLUSION: The results suggest that orthoses could be an effective intervention for back pain and muscle strengthening in osteoporotic women. CLINICAL RELEVANCE: In women with established osteoporosis, wearing Spinomed orthosis for at least 2 h/day for 6 months decreased back pain significantly and increased personal isometric trunk muscle strength. All spinal orthoses could be valuable instruments to help all requested rehabilitation programs like spine muscles' strengthening and postural correct behavior, but only when used properly. PMID- 25138114 TI - Effects of physical exertion on trans-tibial prosthesis users' ability to accommodate alignment perturbations. AB - BACKGROUND: It has long been reported that a range of prosthesis alignments is acceptable in trans-tibial prosthetics. This range was shown to be smaller when walking on uneven surfaces. It has also been argued that findings on gait with prostheses that were obtained under laboratory conditions are limited in their applicability to real-life environments. OBJECTIVES: This study investigated the hypothesis that efforts to compensate for suboptimal alignments by active users of trans-tibial prostheses become less effective when levels of physical exertion increase. STUDY DESIGN: A 2 * 2 repeated-measures analysis of variance was conducted to compare the effects of physical exertion and subtle alignment perturbations on gait with trans-tibial prostheses. METHODS: The gait of eight subjects with trans-tibial amputation was analyzed when walking with two different prosthesis alignments and two different physical exertion levels. The main and interaction effects were statistically evaluated. RESULTS: Bilateral step length symmetry and measures of step variability within the same leg were found to be affected by the intervention. There was no significant effect on index variables that combined kinematic or kinetic measures. CONCLUSION: Findings showed that persons with trans-tibial prostheses responded heterogeneously to the interventions. For most variables, the research hypothesis could not be confirmed. CLINICAL RELEVANCE: Findings support the practice of allotting several sessions to the alignment of trans-tibial prostheses, as users' gait responds differently to perturbations when external factors (e.g. exertion) change. Furthermore, the found inhomogeneity in the population of persons with trans tibial amputation supports the use of technical gait assessment methods in clinical practice. PMID- 25138116 TI - Political parties must tackle racial discrimination against staff and patients. PMID- 25138117 TI - A prospective cross-sectional study on quality of life and treatment satisfaction in type 2 diabetic patients with retinopathy without other major late diabetic complications. AB - BACKGROUND: To assess quality of life and treatment satisfaction in patients with type 2 diabetes mellitus with diabetic retinopathy (DR) using validated instruments, with comparison to patients without DR. METHODS: A prospective cross sectional study was designed to assess the influence of retinopathy on quality of life and treatment satisfaction in patients with type 2 diabetes mellitus who do not have any other advanced late complications that could interfere with these outcomes. We included 148 patients with DR and 149 without DR, all without other advanced diabetic complications. Quality of life was assessed using the Audit of Diabetes Dependent Quality of Life (ADDQoL) questionnaire, and treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Clinical and treatment variables related to diabetes were also collected. The degree of DR was classified according to the International Clinical Classification System. Multivariate linear regression models were used to model the ADDQoL and DTSQ scores according to sociodemographical and clinical characteristics, and to model the adjusted relationship of DTSQ with ADDQoL. In DR patients, a subanalysis assessed the relationship of these scores with the degree of retinopathy, severity of macular edema, and previous photocoagulation treatment. RESULTS: DR was associated with significantly lower quality of life (p < 0.001), when examining the two general quality of life items and most of the specific domains. Concerning DTSQ, no difference was found in the total score, and only two domains that assess the perception of glycemic control (hyper- and hypoglycemia) showed a worse score in DR (p < 0.001 and p = 0.008, respectively). Quality of life was significantly affected by the severity of DR, and treatment satisfaction was significantly affected by the severity of macular edema. In the multivariate analysis, a significant effect of the interaction between diabetes duration, insulin therapy, and the presence of DR was found for both, ADDQoL and DTSQ. CONCLUSION: In the absence of other major complications, DR has a negative impact on quality of life in patients with type 2 diabetes. Further, treatment satisfaction was not affected by the presence of DR. PMID- 25138119 TI - Isolation of a dihydrobenzofuran lignan, icariside E4, with an antinociceptive effect from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark. AB - The antinociceptive activity of icariside E4, a dihydrobenzofuran-type lignan isolated from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark, was evaluated in mice by using chemical and thermal models of nociception. Intraperitoneal (i.p.) administration of crude T. roseo-alba bark extract and its methanol fraction inhibited acetic acid-induced abdominal constriction in mice. Furthermore, i.p. administration of 0.1, 1, and 10 mg/kg of icariside E4 reduced the number of writhes evoked by acetic acid injection by 46.9, 82.3, and 66.6%, respectively. Icariside E4 administration had no effect in the first phase of the formalin test, but it reduced nociceptive behavior in the second phase as indicated by a reduction in the licking time. Icariside E4 did not modify thermal nociception in the hot-plate test model, suggesting that it had a peripheral antinociceptive action. The antinociceptive effect of icariside E4 in the writhing test was reversed by pre-administration of glibenclamide, but not of naloxone, atropine, yohimbine, or haloperidol. Together, these results indicated that the antinociceptive activity of icariside E4 from T. roseo-alba in models of chemical pain occurred through ATP-sensitive K(+) channel-dependent mechanisms. PMID- 25138120 TI - Using gene genealogies to detect rare variants associated with complex traits. AB - BACKGROUND AND OBJECTIVE: Standard population genetic theory says that deleterious genetic variants are likely rare and fairly recently introduced. However, can this expectation lead to more powerful tests of association between diseases and rare genetic variation? The gene genealogy describes the relationships between haplotypes sampled from the general population. Although ancestral tree-based methods, inspired by the gene genealogy concept, have been developed for finding associations with common genetic variants, here we ask whether gene genealogies can help in identifying genomic regions containing multiple rare causal variants. METHODS: With data simulated under several demographic models and using known gene genealogies, we developed and compared several tree-based statistics to determine which, if any, could detect the type of clustering expected with rare causal variants and whether the genealogic tree provides additional information about disease associations. RESULTS AND CONCLUSIONS: We found that a novel statistic based on the scaled distance between the tips of a tree performed better than other tree-based statistics. When data were simulated with mild population growth, this statistic outperformed two standard non-tree-based methods, showing that an ancestral tree-based approach has potential for rare variant discovery. PMID- 25138121 TI - Oral viscous budesonide as a first-line approach to esophageal stenosis in epidermolysis bullosa: an open-label trial in six children. AB - BACKGROUND: Esophageal and pharyngeal problems are common in the majority of patients with epidermolysis bullosa (EB). Repeated blister formation and ulceration, coupled with chronic inflammation, result in scarring and development of esophageal strictures. OBJECTIVE: This study aimed to evaluate whether oral viscous budesonide (OVB) was useful for treating esophageal structures in six pediatric patients (aged 8-17 years) with EB who were affected by dysphagia and esophageal strictures. METHODS: Patients were treated for 4 months with twice daily oral budesonide nebulizer solution 0.5 mg/2 mL mixed with maltodextrin 5 g and artificial sweeteners. RESULTS: One patient developed a severe oral mycotic infection and discontinued treatment. The other five patients completed the treatment regimen and displayed significantly lower stricture indices (SIs) post treatment (mean SI +/- standard deviation 0.736 +/- 0.101 pre-treatment versus 0.558 +/- 0.162 post-treatment; p = 0.008). Patients experienced a mean SI decrease of 0.178 (range 0.026-0.296), as well as improved dietary habits in the absence of side effects. CONCLUSION: These findings indicated that topical corticosteroids may significantly alleviate strictures in pediatric patients with EB, thereby limiting the need for endoscopic dilation and considerably improving patients' quality of life. PMID- 25138122 TI - Perioperative and postoperative complications after Ophira mini sling operations. AB - AIM: To evaluate perioperative and postoperative complications of mini sling operations in the surgical treatment of female urinary incontinence. METHODS: The study was comprised of 151 female patients with stress urinary incontinence (SUI) or mixed incontinence (MUI) with predominant SUI patients who underwent the mini sling procedure. The duration of the follow-up ranged from 6 to 21 months. All women had positive cough stress tests preoperatively. The procedure was performed under local (86.1 %) or spinal anesthesia (13.9 %) with the same mini slings for all cases. Patients were examined in the outpatient clinic at 1 and 6 months after surgery. RESULTS: The mean age was 49 years old (SD 10) with a range of 26 82. Of the 151 patients, 42 (27.8 %) presented MUI, while 109 (72.2 %) presented SUI. Mean parity was 3 +/- 1. Mean body mass index was 28.9 +/- 3.5. 60 (39.7 %) of the cases were postmenopausal. There were 73 women who participated in 6 months follow-ups and 78 women who did 1-year follow-ups. The mean operating time was 13 +/- 3.1 min. There were no major intraoperative complications due to mini sling surgery. 120 (79.5 %) patients were discharged the day following the surgery. Ten patients (6.1 %) had de novo urge incontinence in their post operative follow-ups which was resolved using anti-cholinergic drugs. Two patients (1.2 %) required sling sections due to prolonged bladder outlet obstruction. There were 15 patients that complained about de novo dyspareunia (9.9 %). Vaginal mesh extrusion was reported in 18 (11.9 %) patients. The mean preoperative and postoperative hemoglobin concentrations were 12.9 +/- 1.3 and 12.5 +/- 1.3 g/dL, respectively. CONCLUSION: The mini sling system can be considered an easy and effective method for treating stress urinary incontinence without major complication rates. PMID- 25138123 TI - The effect of physical exercise on postpartum fitness, hormone and lipid levels: a randomized controlled trial in primiparous, lactating women. AB - PURPOSE: To evaluate the effect of an exercise training program combining low impact dance aerobic, resistance and stretching exercise on physical fitness, hormone and lipid levels of postpartum, primiparous, lactating women. METHODS: Thirty seven primiparous, lactating women were randomly assigned at 4-6 weeks postpartum to either follow an exercise training program of 50-60 min aerobic, strengthening and stretching exercise, 3 days a week, for 12 weeks (interventional group; n = 20) or no training program at all (control group; n = 17). The following parameters were measured at baseline and 12 weeks later: (1) for evaluation of physical fitness: VO2max, muscular endurance, joint mobility and body fat; (2) for evaluation of the lipidemic profile: triglyceride, total cholesterol, HDL and LDL levels, and (3) levels of hormones associated with lactation: prolactin, estradiol, cortisol, TSH, fT3 and fT4. RESULTS: After completion of the exercise training program, comparisons between the interventional and the control group showed statistically significant mean changes in VO2max (p = 0.003), muscular endurance of the upper extremities (p < 0.001), and the abdomen (p < 0.001), flexibility (p = 0.042), and body fat (p = 0.007). There were no significant differences between the two groups in mean changes of lipid and hormone levels. CONCLUSION: Implementation of a low-impact exercise training program appears to improve physical fitness of postpartum women, while it does not seem to affect lipid levels and lactation-associated hormone levels. Hence, implementation of an exercise training program combining low-impact dance aerobic, resistance and stretching exercise is feasible in postpartum, primiparous, lactating women. PMID- 25138124 TI - Cervical cancer screening in Germany: group-specific participation rates in the state of Niedersachsen (Lower Saxony). A study with health insurance data. AB - PURPOSE: The participation rates in cervical screenings are varying over different countries. This is only partly due to the availability of organized screening programs, as the rates are also varying between countries were such programs were implemented. For Germany the level of knowledge is low, and information are outdated. In order to improve the level of knowledge, we examined whether the participation rates in cervical screenings in a large German insurance population were changing over time, and whether these changes were different with respect to age and qualification of the participating women. METHODS: The analyses were based on the complete anonymised dataset of a large statutory health insurance in Lower Saxony, Germany, with case numbers between 940,827 (2006) and 1,044,797 (2011) women aged 20 years and older. RESULTS: Between 2006 and 2011 the overall annual participation rates were increasing from 44.8 to 47.6%. The highest rates occurred in women with the highest qualification level, thus leading to increasing social differences over time. There was a peak in the age group of 25-29 years from annually 60.3 (2006) to 60.2% (2011), and bi annually from 77 to 77.1% with constantly decreasing rates up to the age of 60. No substantial differences occurred between a 2- and a 3-year observation period. CONCLUSIONS: Over time only small increases of participation rates in cervical screenings occurred. These findings may be interpreted in favor of population based screenings within an invitation program. PMID- 25138125 TI - Associations between adipocyte fatty acid-binding protein and clinical parameters in polycystic ovary syndrome. AB - PURPOSE: We evaluated a possible association between serum adipocyte fatty acid binding protein (A-FABP) levels and clinical parameters in women with polycystic ovary syndrome (PCOS). METHODS: Our study included 86 women: 49 with PCOS (study group), 37 with non-PCOS (control group). We recorded and analyzed age, body mass index [BMI = weight (kg)/height (m)(2)], waist circumference, and blood pressure and follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, free testosterone (fT), dehydroepiandrosterone sulfate, 17-OH progesterone, insulin, glucose, triglyceride, high-density lipoprotein, low-density lipoprotein, very low density lipoprotein, HOMA-IR, and A-FABP levels. RESULTS: The mean BMI, waist circumference, and levels of serum LH, fT, LH/FSH, fasting insulin, and HOMA-IR were significantly higher in PCOS patients (p < 0.05). Pearson correlation analysis showed positive correlations of A-FABP levels with BMI and HOMA-IR levels and a negative correlation between A-FABP and fT levels. A ROC curve analysis found that BMI, waist circumference, and levels of fT, A-FABP, and HOMA IR were discriminative parameters. CONCLUSION: Serum A-FABP levels may be a good prognostic marker in predicting metabolic syndrome and cardiovascular diseases in PCOS patients. PMID- 25138126 TI - The influence of body weight on sexual function and quality of life in women with polycystic ovary syndrome. AB - PURPOSE: To assess sexual function (SF) and quality of life (QOL) in women with polycystic ovary syndrome (PCOS). METHODS: A cross-sectional study was conducted to assess 56 women with PCOS and 102 control women with regular menstrual cycles. To assess SF and QOL in Brazilian women with PCOS with Female Sexual Function Index (FSFI) and the WHOQOL-bref questionnaires. RESULTS: Women with PCOS had a worse evaluation to arousal, lubrication, satisfaction, pain and total FSFI, and there was no difference in sexual desire and orgasm. Besides, they had a worse evaluation concerning health status than controls. The body mass index was inversely correlated to the QOL, especially to the physical, psychological, environment aspects and self-assessment of QOL, but it did not show correlation to the SF. CONCLUSION: Women with PCOS had a worse sexual function and self assessment of health condition in comparison to controls. The body weight as isolated symptom was correlated to the worsening in quality of life, but not with the worsening of sexual function. PMID- 25138127 TI - Effects of electro-acupuncture on labor pain management. AB - PURPOSE: To evaluate the effects of a non-pharmacologic electro-acupuncture method at different acupoints on labor pain management. METHODS: Nulliparous women under the maternity care of the Department of Obstetrics and Gynecology of Sir Run Run Shaw Hospital were recruited and allocated into two experimental groups (EX-B2 group and SP6 group) and one control group, each with 60 eligible participants. Visual analog scale (VAS) was used to assess the pain during active phase of labor before and 30, 60, 120 min after intervention. The duration of active phase, the duration of second stage of labor, the duration of third stage of labor, use of oxytocin, neonatal birth weight, neonatal Apgar score at 1 and 5 min were considered as secondary outcomes of this study. RESULTS: After 30 min intervention, the mean VAS scores of both EX-B2 group and SP6 group were significantly decreased compared with the control group (P < 0.01); however, no significant difference was observed between the two experimental groups (P > 0.05). After 60 and 120 min intervention, the mean VAS scores of EX-B2 group were significantly lower than SP-6 group (P < 0.05). Both EX-B2 group and SP6 group had significant lower VAS scores after interventions and shorter time used in active phase of labor than the control group (P < 0.05). CONCLUSIONS: The study revealed that the application of electro-acupuncture at EX-B2 and SP6 acupoints could be used as a non-pharmacologic method to reduce labor pain and shorten the duration of active phase of labor. PMID- 25138128 TI - Oral versus vaginal misoprostol for induction of labor in Enugu, Nigeria: a randomized controlled trial. AB - OBJECTIVE: The study aimed at comparing the effectiveness and maternal satisfaction of oral misoprostol with vaginal misoprostol for induction of labor at term. MATERIALS AND METHODS: A randomized controlled trial of 140 term pregnant women at the University of Nigeria Teaching Hospital Enugu, Nigeria, was conducted from April 2011 to May 2012. The women were equally randomized into two groups (A and B) to receive oral and vaginal misoprostol, respectively. RESULTS: The vaginal route reduced the mean induction-vaginal delivery interval by four and-half hours (20.7 +/- 12.1 vs. 16.2 +/- 10.4; mean difference: 4.50, 95% CI 0.63-0.82; p = 0.02). Furthermore, the mean dose of misoprostol required to achieve induction of labor and the mean duration of oxytocin augmentation when indicated were significantly less in the vaginal group than in the oral group (2.5 +/- 1.3 vs. 2.0 +/- 1.1; mean difference: 0.50, 95% CI 0.10-0.90; p = 0.02 and 4.6 +/- 3.2 vs. 3.4 +/- 3.1; mean difference: 1.20, 95% CI 0.15-0.23; p = 0.03 respectively). However, neonatal complications and maternal satisfaction were similar between the two groups. CONCLUSION: Both routes of administration are effective in the induction of labor at term and have comparable maternal satisfaction. However, the vaginal route has the added advantage of shorter induction-delivery interval among others, and thus should be highly considered when induction of labor is indicated at term. PMID- 25138130 TI - Advances in chalcones with anticancer activities. AB - Chalcones are naturally occurring compounds exhibiting broad spectrum biological activities including anticancer activity through multiple mechanisms. Literature on anticancer chalcones highlights the employment of three pronged strategies, namely; structural manipulation of both aryl rings, replacement of aryl rings with heteroaryl scaffolds, molecular hybridization through conjugation with other pharmacologically interesting scaffolds for enhancement of anticancer properties. Methoxy substitutions on both the aryl rings (A and B) of the chalcones, depending upon their positions in the aryl rings appear to influence anticancer and other activities. Similarly, heterocyclic rings either as ring A or B in chalcones, also influence the anticancer activity shown by this class of compounds. Hybrid chalcones formulated by chemically linking chalcones to other prominent anticancer scaffolds such as pyrrol[2,1-c][1,4]benzodiazepines, benzothiazoles, imidazolones have demonstrated synergistic or additive pharmacological activities. The successful application of these three pronged strategies for discovering novel anticancer agents based on chalcone scaffold has resulted in many novel and chemically diverse chalcones with potential therapeutic application for many types of cancer. This review summarizes the concerted efforts expended on the design and development of anticancer chalcones recorded in recent literature and also provides an overview of the patents published in this area between 2007 and 2014 (WO2013022951, WO201201745 & US2012029489). PMID- 25138129 TI - Identification of myeloid-derived suppressor cells in the synovial fluid of patients with rheumatoid arthritis: a pilot study. AB - BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of innate immune cells with a granulocyte-like or monocyte-like phenotype and a unique ability to suppress T-cell responses. MDSCs have been shown to accumulate in cancer patients, but recent studies suggest that these cells are also present in humans and animals suffering from autoimmune diseases. We previously identified MDSCs in the synovial fluid (SF) of mice with experimental autoimmune arthritis. The goal of the present study was to identify MDSCs in the SF of patients with rheumatoid arthritis (RA). METHODS: RA SF cells were studied by flow cytometry using antibodies to MDSC cell surface markers as well as by analysis of cell morphology. The suppressor activity of RA SF cells toward autologous peripheral blood T cells was determined ex vivo. We employed both antigen-nonspecific (anti-CD3/CD28 antibodies) and antigen-specific (allogeneic cells) induction systems to test the effects of RA SF cells on the proliferation of autologous T cells. RESULTS: SF from RA patients contained MDSC like cells, the majority of which showed granulocyte (neutrophil)-like phenotype and morphology. RA SF cells significantly suppressed the proliferation of anti CD3/CD28-stimulated autologous T cells upon co-culture. When compared side by side, RA SF cells had a more profound inhibitory effect on the alloantigen induced than the anti-CD3/CD28-induced proliferation of autologous T cells. CONCLUSION: MDSCs are present among RA SF cells that are commonly regarded as inflammatory neutrophils. Our results suggest that the presence of neutrophil like MDSCs in the SF is likely beneficial, as these cells have the ability to limit the expansion of joint-infiltrating T cells in RA. PMID- 25138131 TI - Patent analysis as a tool for research planning: study on natural based therapeutics against cancer stem cells. AB - Medicines developed from traditional systems are well known for their various important pharmaceutical uses. Cancer has been known since ancient times and has been mentioned in the ancient Ayurvedic books. Thus natural based products play a significant role in cancer chemotherapeutics. Further, approximately 70% of anticancer compounds are based on natural products or have been derived from their structural scaffolds. Hence, there is a growing interest for developing medicines from these natural resources. Amongst the methods of treating cancer, therapies targeting cancer stem cell are found to control metastatic tumor which is a newly identified factor associated with relapse. This patent review aims to highlight the use of natural products to treat cancer by targeting the cancer stem cells. The review will also provide insights into the reported mechanisms by which the natural products act in order to suppress or kill cancer stem cells. The analysis has been done using various criteria such as the patenting trend over the years, comparison of active assignee and a comparison of the technical aspects as disclosed in the different patent documents. The analysis further highlights different bioactives, the scaffolds of which could thus be a promising candidate in the development of anti-cancer drugs by targeting the cancer stem cells. The technical aspects covered in this review include: Bioactives and formulations comprising the extracts or bioactives, their mode of action and the type of assay considered to study the efficacy of the natural products. Further the mapping has helped us to identify potential therapeutic areas to evaluate herbs/bioactives and their uses for developing new formulations. PMID- 25138132 TI - Fetal myelomeningocele repair: the post-MOMS experience at the Children's Hospital of Philadelphia. AB - BACKGROUND: Fetal myelomeningocele (fMMC) repair has become accepted as a standard of care option in selected circumstances. We reviewed our outcomes for fMMC repair from referral and evaluation through surgery, delivery and neonatal discharge. MATERIAL AND METHODS: All patients referred for potential fMMC repair were reviewed from January 1, 2011 through March 7, 2014. Maternal and neonatal data were collected on the 100 patients who underwent surgery. RESULTS: 29% of those evaluated met the criteria and underwent fMMC repair (100 cases). The average gestational age was 21.9 weeks at evaluation and 23.4 weeks at fMMC repair. Complications included membrane separation (22.9%), preterm premature rupture of membranes (32.3%) and preterm labor (37.5%). Average gestational age at delivery was 34.3 weeks and 54.2% delivered at >=35 weeks. The perinatal loss rate was 6.1% (2 intrauterine fetal demises and 4 neonatal demises); 90.8% of women delivered at the Children's Hospital of Philadelphia and 3.4% received transfusions. With regard to the neonates, 2 received ventriculoperitoneal shunts prior to discharge; 71.1% of neonates had no evidence of hindbrain herniation on MRI. Of the 80 neonates evaluated, 55% were assigned a functional level of one or more better than the prenatal anatomic level. CONCLUSION: In an experienced program, maternal and neonatal outcomes for patients undergoing fMMC repair are comparable to results of the MOMS trial. PMID- 25138134 TI - Cytomegalovirus central nervous system compartmentalization in a patient presenting with AIDS. AB - Cytomegalovirus (CMV) central nervous system involvement is uncommon and hardly diagnosed because it can mimic many different conditions. We here present a case of an HIV-positive patient with neurological signs and symptoms (headache, asthenia, confusion, hallucinations, ataxia) with concurrent opportunistic diseases (neurotoxoplasmosis, disseminated Kaposi's sarcoma, disseminated CMV infection). CMV CNS involvement was not initially considered given the observed multiple comorbidities: antiviral treatment duration was probably not adequate given the end-organ disease. Concomitantly, plasma CMV DNA was undetectable while cerebrospinal fluid viral load was 31,340 copies/ml. Ganciclovir treatment followed by oral valganciclovir maintenance was associated with the slow disappearance of symptoms, the improvement of MRI images and the persistent undetectability of CMV DNA. The case here reported highlights the challenges of diagnosing CMV encephalitis in HIV-positive patients (with several cerebral comorbidities), the incomplete knowledge of the appropriate treatment for such a disease and the possibility of CMV replication in the cerebrospinal fluid despite undetectable plasma CMV DNA. PMID- 25138135 TI - A vanishing lymphoma in the cheek. AB - BACKGROUND: We describe the unusual case of a 66-year-old woman who presented with a cheek mass that completely abated with oral steroids. CASE REPORT: Multiple separate biopsies of the mass were negative or inconclusive. MRI revealed a large mass, yet after a short steroid course, this mass was completely undetectable on clinical examination. A repeat biopsy eventually revealed follicular lymphoma. DISCUSSION: Lymphomas are known to be steroid sensitive; the medication is an essential component of the common CHOP therapy. While known to occur in the central nervous system, to the best of our knowledge, the presence of a 'vanishing' lymphoma has not been documented in the head and neck. We discuss the likely physiology of the vanishing lymphoma, and the diagnostic difficulty it presents. CONCLUSION: When a lymphoma is suspected, patient care may be optimized if biopsy is delayed until steroids have been discontinued. PMID- 25138136 TI - The association between family meals and early-adolescents' weight status change in the context of parental discipline practices: the moderating roles of ethnicity and acculturation. AB - This study examines the interactions among family meals, parental discipline practices, ethnicity, and acculturation on weight status change in a diverse sample of early-adolescents. Data were obtained from the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K), a nationally representative sample of children who entered kindergarten during 1998-1999. In fifth grade, parents reported on child and household routines. In fifth and eighth grade, children were weighed and measured at school. Above and beyond covariates, less acculturated Hispanic adolescents who ate more family meals and experienced low parental behavioral control in fifth grade were less likely to make a healthy change (gamma = -0.15, OR = 0.86, p < 0.05) and more likely to make an unhealthy change (gamma = 0.32, OR = 1.38, p < 0.05) in their weight status by eighth grade, when compared to White Non-Hispanic adolescents. The implications of interactions among family meals, parental discipline practices, and healthy weight promotion are discussed in the context of ethnicity and acculturation. PMID- 25138137 TI - Disparities in Access to Prenatal Care Services for African Immigrant Women in Spain. AB - This retrospective cohort study compares the utilization of prenatal care between African immigrant and native Spanish women. For 2007-2010, we identified 231 pregnant African immigrant women. The native-born population sample was obtained by simple random sampling in a 1:3 ratio. The Kessner Index (KI) and our Own Index (OI) were applied to rate prenatal care adequacy in three categories (adequate, intermediate, and inadequate). Odds ratios (ORs) were estimated using non-conditional logistic regression. Prenatal care was adequate according to the indexes (KI or OI) in 21.3 and 25.8% of North Africans and in 22.5 and 30.4% of sub-Saharan Africans. The ORs of inadequacy when adjusted for maternal age, social risk factors, and previous reproductive outcomes were 30.32 and 35.47 (KI or OI) in North and 64.43 and 67.93 in sub- Saharan Africans. These results suggest significant differences in obtaining adequate prenatal care between immigrant and native Spanish women. PMID- 25138138 TI - Evaluating Job Demands and Control Measures for Use in Farm Worker Health Surveillance. AB - Workplace stress likely plays a role in health disparities; however, applying standard measures to studies of immigrants requires thoughtful consideration. The goal of this study was to determine the appropriateness of two measures of occupational stressors ('decision latitude' and 'job demands') for use with mostly immigrant Latino farm workers. Cross-sectional data from a pilot module containing a four-item measure of decision latitude and a two-item measure of job demands were obtained from a subsample (N = 409) of farm workers participating in the National Agricultural Workers Survey. Responses to items for both constructs were clustered toward the low end of the structured response-set. Percentages of responses of 'very often' and 'always' for each of the items were examined by educational attainment, birth country, dominant language spoken, task, and crop. Cronbach's alpha, when stratified by subgroups of workers, for the decision latitude items were (0.65-0.90), but were less robust for the job demands items (0.25-0.72). The four-item decision latitude scale can be applied to occupational stress research with immigrant farm workers, and potentially other immigrant Latino worker groups. The short job demands scale requires further investigation and evaluation before suggesting widespread use. PMID- 25138139 TI - Sensitivity and false alarm rate of a fall sensor in long-term fall detection in the elderly. AB - BACKGROUND: About a third of home-dwelling older people fall each year, and institutionalized older people even report a two- or threefold higher rate for falling. Automatic fall detection systems have been developed to support the independent and secure living of the elderly. Even though good fall detection sensitivity and specificity in laboratory settings have been reported, knowledge about the sensitivity and specificity of these systems in real-life conditions is still lacking. OBJECTIVE: The aim of this study was to evaluate the long-term fall detection sensitivity and false alarm rate of a fall detection prototype in real-life use. METHODS: A total of 15,500 h of real-life data from 16 older people, including both fallers and nonfallers, were monitored using an accelerometry-based sensor system with an implemented fall detection algorithm. RESULTS: The fall detection system detected 12 out of 15 real-life falls, having a sensitivity of 80.0%, with a false alarm rate of 0.049 alarms per usage hour with the implemented real-time system. With minor modification of data analysis the false alarm rate was reduced to 0.025 false alarms per hour, equating to 1 false fall alarm per 40 usage hours. CONCLUSION: These data suggest that automatic accelerometric fall detection systems might offer a tool for improving safety among older people. PMID- 25138140 TI - Temporary arterial embolization of liver parenchyma with degradable starch microspheres (EmboCept(r)S) in a swine model. AB - BACKGROUND: This study aimed to evaluate the embolic properties, time to reperfusion, and histologic changes in temporary embolization of liver tissue with degradable starch microspheres (DSM) in a swine model. METHODS: In four adult minipigs, DSMs were injected into the right or left hepatic artery on the lobar level until complete stasis of the blood flow was detectable angiographically. The time required to complete angiographically determined reperfusion was noted. The animals were killed 3 h after complete reperfusion, and samples were taken from the liver. Histologic examinations of the embolized liver parenchyma and untreated tissue were performed. RESULTS: Hepatic arterial embolization using DSMs was technically successful in all cases, with complete blood flow stasis shown by control angiography. A single vial of DSMs (450 mg/7.5 ml) was sufficient to embolize a whole liver lobe in all cases. Angiography showed complete reconstitution of hepatic arterial perfusion after a mean time to reperfusion of 32 +/- 6.1 min (range, 26-39 min). Hematoxylin and eosin staining showed no histologically detectable differences between untreated tissue and parenchyma embolized with DSMs except for mild sinusoidal congestion in one case. Indirect in situ DNA nick end labeling staining (TUNEL) showed only single positive hepatocytes, indicating apoptosis. CONCLUSION: Temporary embolization of the hepatic artery using DSMs is feasible with complete reperfusion after 30 min in pigs. Even after complete arterial blood flow stasis, no extensive tissue damage to the embolized liver parenchyma was observed at histologic examinations in this short-term study. PMID- 25138141 TI - Antibacterial activity of biogenic silver nanoparticles synthesized with gum ghatti and gum olibanum: a comparative study. AB - Presently, silver nanoparticles produced by biological methods have received considerable significance owing to the natural abundance of renewable, cost effective and biodegradable materials, thus implementing the green chemistry principles. Compared with the nanoparticles synthesized using chemical methods, most biogenic silver nanoparticles are protein capped, which imparts stability and biocompatibility, and enhanced antibacterial activity. In this study, we compared the antibacterial effect of two biogenic silver nanoparticles produced with natural plant gums: gum ghatti and gum olibanum against Gram-negative and Gram-positive bacteria. Bacterial interaction with nanoparticles was probed both in planktonic and biofilm modes of growth; employing solid agar and liquid broth assays for inhibition zone, antibiofilm activity, inhibition of growth kinetics, leakage of intracellular contents, membrane permeabilization and reactive oxygen species production. In addition, cytotoxicity of the biogenic nanoparticles was evaluated in HeLa cells, a human carcinoma cell line. Antibacterial activity and cytotoxicity of the silver nanoparticles synthesized with gum ghatti (Ag NP-GT) was greater than that produced with gum olibanum (Ag NP-OB). This could be attributed to the smaller size (5.7 nm), monodispersity and zeta potential of the Ag NP-GT. The study suggests that Ag NP-GT can be employed as a cytotoxic bactericidal agent, whereas Ag NP-OB (7.5 nm) as a biocompatible bactericidal agent. PMID- 25138143 TI - Contact lenses: new devices for nucleotide delivery in ocular pathologies. PMID- 25138142 TI - Vancomycin blocks autophagy and induces interleukin-1beta release in macrophages. AB - Systemic inflammatory response syndrome (SIRS) is a serious condition that can cause organ failure as an exaggerated immunoresponse to the infection or other causes. Recently, autophagy was reported as a key process that regulates inflammatory responses in macrophages. Vancomycin is one of the most commonly prescribed antibiotics for sepsis treatment or following surgery. However, there are no studies on how vancomycin affects autophagy or inflammation. Here, we treated macrophage cell lines with vancomycin and lipopolysaccharides and found that vancomycin blocks autophagy and increases inflammatory responses. This finding suggests that vancomycin should be more cautiously administered in order to prevent unwanted SIRS during sepsis. PMID- 25138144 TI - Treatment moderators of cognitive behavior therapy to reduce aggressive behavior: a meta-analysis. AB - Maladaptive aggression in adolescents is an increasing public health concern. Cognitive Behavior Therapy (CBT) is one of the most common and promising treatments of aggression. However, there is a lack of information on predictors of treatment response regarding CBT. Therefore, a meta-analysis was performed examining the role of predictors on treatment response of CBT. Twenty-five studies were evaluated (including 2,302 participants; 1,580 boys and 722 girls), and retrieved through searches on PubMed, PsycINFO and EMBASE. Effect sizes were calculated for studies that met inclusion criteria. Study population differences and specific CBT characteristics were examined for their explanatory power. There was substantial variation across studies in design and outcome variables. The meta-analysis showed a medium treatment effect for CBT to reduce aggression (Cohen'd = 0.50). No predictors of treatment response were found in the meta analysis. Only two studies did examine whether proactive versus reactive aggression could be a moderator of treatment outcome, and no effect was found of this subtyping of aggression. These study results suggest that CBT is effective in reducing maladaptive aggression. Furthermore, treatment setting and duration did not seem to influence treatment effect, which shows the need for development of more cost-effective and less-invasive interventions. More research is needed on moderators of outcome of CBT, including proactive versus reactive aggression. This requires better standardization of design, predictors, and outcome measures across studies. PMID- 25138146 TI - Bioinspired design and assembly of layered double hydroxide/poly(vinyl alcohol) film with high mechanical performance. AB - Inspired by the hierarchical structure and excellent mechanical performance of nacre, LDH nanosheets with an appropriate aspect ratio to withstand significant loads and at the same time allow for rupture under the pull-out mode were synthesized as artificial building blocks for the fabrication of nacre-like films. Multilayered PVA/LDH films with a high tensile strength and ductility were prepared for the first time by bottom-up layer-by-layer assembly of pretreated LDH nanosheets and spin-coating of PVA. The weight fraction of inorganic LDH platelets in the hybrid PVA/LDH films (wp) was controlled by changing the concentration of PVA solution applied in the spin-coating process. The resulting films revealed that the PVA/LDH hybrid films were piled close together to form a well-defined stratified structure resembling the brick-and-mortar structure of natural nacre. In the hybrid films, the content of inorganic LDH platelets was comparable to the value in nacre, up to 96.9 wt %. It could be clearly seen that the mechanical performance of the as-prepared PVA/LDH films was greatly improved by increasing the rigid building-block LDHs. The tensile strength of the 2 wt % PVA/LDH hybrid film reached a value of 169.36 MPa, thus exceeding the strength of natural nacre and reaching 4 times that of a pure PVA film. Meanwhile, its elastic modulus was comparable to that of lamellar bone. PMID- 25138147 TI - Relationships between the effect of sunitinib and immature blood vessels in metastatic renal cell cancer. AB - INTRODUCTION: This study was conducted to investigate the relationships between the effect of sunitinib and immature microvessels which are not covered by pericytes. MATERIALS AND METHODS: This study involved 29 patients with clear-cell renal cell carcinoma (RCC) who took sunitinib after radical nephrectomy or biopsy due to metastatic RCC. Associations among clinicopathological factors, responses to sunitinib, and patient survival were reviewed. CD31 was used to stain endothelial cells, and anti-alpha-smooth muscle actin was used to stain pericytes. Immature vessels were defined as vessels that were positive only for CD31 staining. A high pericyte coverage was defined as a rate of pericyte coverage above 40%. RESULTS: Partial responses, disease stabilization, and disease progression constituted 51.7, 10.4, and 37.9% of cases, respectively. Nine cases had a low pericyte coverage (31.0%). In the high-pericyte-coverage group, the number of metastatic sites was smaller (p=0.003). The overall response rate to sunitinib was greater in the high-pericyte-coverage group than in the low pericyte-coverage group (p=0.027). The median overall survival and the median progression-free survival were not significantly different between the high- and low-pericyte-coverage groups. CONCLUSION: In the high-pericyte-coverage group, the overall response rates to sunitinib were higher, and the numbers of metastatic sites were smaller. PMID- 25138145 TI - Chronic multisite pain in adolescent girls and boys with emotional and behavioral problems: the Young-HUNT study. AB - The aim of this study was to assess the prevalence of chronic multisite pain with high disability in relation to emotional or behavioral problems and resilience factors in adolescence. A second aim was to investigate if resilience factors could attenuate the associations between psychiatric symptoms and chronic multisite pain. The study was based on a large cross-sectional study carried out in Norway between 2006 and 2008 and included 7,070 adolescents aged 13-19 years. Chronic multisite pain was defined as pain at least once a week during the last 3 months, scoring high on a disability index, and occurring in three or more locations. Chronic multisite pain was prevalent among adolescents with high scores (>85%) for anxiety/depression, social anxiety, conduct or attention problems (22.8-31.0 for girls, 8.8-19.0% for boys). Several coexistent psychiatric symptoms increased the prevalence of chronic multisite pain for both girls and boys. Resilience factors, including high self-esteem, seldom feeling lonely, and high scores for family cohesion or social competence, were associated with a lower prevalence and markedly attenuated the association between psychiatric symptoms and chronic multisite pain. Psychiatrists should be careful to assess and treat comorbid chronic pain in adolescents with emotional or behavioral problems. PMID- 25138148 TI - Donor-transmitted HTLV-1-associated myelopathy in a kidney transplant recipient- case report and literature review. AB - Clinical disease due to human T cell lymphotropic virus type 1 (HTLV-1), a retrovirus endemic in certain regions of the world, is rarely reported after solid organ transplantation. In 2009, universal deceased donor organ screening for HTLV-1 was discontinued in the United States. We report the first case of donor-derived HTLV-1-associated myelopathy in a kidney transplant recipient from the United States. The patient, who was HTLV-1-seronegative prior to transplantation, likely acquired HTLV-1 infection from a seropositive organ donor. In this era when screening of donors and recipients for HTLV infection is not mandatory, clinicians should be vigilant in recognizing the risk and potential occurrence of this donor-derived infection in recipients with epidemiologic exposures. PMID- 25138150 TI - Micropercutaneous Nephrolithotomy in the Management of Bilateral Renal Stones in a 7-Month-Old Infant: The Youngest Case in the Literature. AB - During infancy, the renal parenchyma and pelvicalyceal system are relatively fragile. Therefore, percutaneous nephrolithotomy for the management of renal stones in this age group is a challenging procedure for urologists. Herein, we present the uneventful management of bilateral renal stones using micropercutaneous nephrolithotomy (microperc) administered to a 7-month-old infant with recurrent urinary tract infections. In this paper, the advantages and disadvantages of the microperc procedure are discussed. As far as we know, our patient is the youngest case in whom the microperc procedure has been performed. PMID- 25138149 TI - Reversible cerebral vasoconstriction syndrome: a comprehensive update. AB - Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiological syndrome characterized by recurrent thunderclap headache, with or without neurologic symptoms, and reversible vasoconstriction of cerebral arteries. RCVS affects patients in various racial and ethnic groups and in all age groups, although most commonly in the fourth decade of life. Many conditions and exposures have been linked to RCVS, including vasoactive drugs and the peripartum period. Disturbance of the cerebral vascular tone is thought to contribute to the disease's pathophysiology. RCVS generally follows a monophasic course. Associated strokes and cerebral hemorrhages are not uncommon. In this review we will attempt to provide a comprehensive overview of RCVS, with emphasis on the controversies in the field and the newest findings in the reported literature. PMID- 25138151 TI - The effectiveness of collaborative care for people with memory problems in primary care: results of the CAREDEM case management modelling and feasibility study. AB - BACKGROUND: People with dementia and their families need support in different forms, but currently services are often fragmented with variable quality of care. Case management offers a way of co-ordinating services along the care pathway and therefore could provide individualised support; however, evidence of the effectiveness of case management for dementia is inconclusive. OBJECTIVE: To adapt the intervention used in a promising case management project in the USA and test its feasibility and acceptability in English general practice. DESIGN: In work package 1, a design group of varied professionals, with a carer and staff from the voluntary sector, met six times over a year to identify the skills and personal characteristics required for case management; protocols from the US study were adapted for use in the UK. The feasibility of recruiting general practices and patient-carer dyads and of delivering case management were tested in a pilot study (work package 2). An embedded qualitative study explored stakeholder views on study procedures and case management. SETTING: Four general practices, two in the north-east of England (Newcastle) one in London and one in Norfolk, took part in a feasibility pilot study of case management. PARTICIPANTS: Community-dwelling people with dementia and their carers who were not already being case managed by other services. INTERVENTION: A social worker shared by the two practices in the north-east and practice nurses in the other two practices were trained to deliver case management. We aimed to recruit 11 people with dementia from each practice who were not already being case managed. MAIN OUTCOME MEASURES: Numbers of people with dementia and their carers recruited, numbers and content of contacts, needs identified and perceptions of case management among stakeholders. RESULTS: Recruitment of practices and patients was slow and none of the practices achieved its recruitment target. It took more than 6 months to recruit a total of 28 people with dementia. Practice Quality and Outcome Framework registers for dementia contained only 60% of the expected number of people, most living in care homes. All stakeholders were positive about the potential of case management; however, only one of the four practices achieved a level of case management activity that might have influenced patient and carer outcomes. Case managers' activity levels were not related solely to time available for case management. Delivery of case management was hindered by limited clarity about the role, poor integration with existing services and a lack of embeddedness within primary care. There were discrepancies between case manager and researcher judgements about need, and evidence of a high threshold for acting on unmet need. The practice nurses experienced difficulties in ring fencing case management time. CONCLUSIONS: The model of case management developed and evaluated in this feasibility study is unlikely to be sustainable in general practice under current conditions and in our view it would not be appropriate to attempt a definitive trial of this model. This study could inform the development of a case management role with a greater likelihood of impact. Different approaches to recruiting and training case managers, and identifying people with dementia who might benefit from case management, are needed, as is exploration of the scale of need for this type of working. TRIAL REGISTRATION: Current Controlled Trials ISRCTN74015152. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 52. See the NIHR Journals Library website for further project information. PMID- 25138152 TI - Vocal fold paresis accompanying vocal fold polyps. AB - The aim of this study was to evaluate patients with vocal fold polyps using laryngeal electromyography (LEMG) for the presence of vocal fold paresis and to compare transnasal fiberoptic and rigid stroboscopic findings between polyp patients with normal LEMG and with vocal fold paresis. Thirty-five patients with a vocal fold polyp underwent transnasal fiberoptic laryngoscopy, rigid laryngostroboscopy, and LEMG. The findings were compared between the LEMG confirmed vocal fold paresis patients and the normal LEMG patients. LEMG resulted in a diagnosis of unilateral or bilateral vocal fold paresis in 17 of 35 patients (48.6 %). More men than women with vocal fold polyps had vocal fold paresis (p < 0.05). The vocal fold paresis group had higher presence of axial rotation and hypomobility of vocal folds, higher asymmetry of vertical height of vocal folds, and less presence of longitudinal stretch of vocal folds (p < 0.05). Medial lateral compression of the false vocal folds and anterior-posterior approximation of the larynx did not show any difference between the groups. No significant difference was found in vibratory wave characteristics between the groups through rigid laryngostroboscopy. Vocal fold paresis was present in almost half of the patients with vocal fold polyps. Paresis can only be accurately diagnosed with LEMG. Transnasal fiberoptic laryngoscopic examination is helpful to recognize vocal fold paresis in vocal fold polyp patients, while stroboscopic examination is not useful to identify it in vocal fold polyp patients. PMID- 25138153 TI - In vivo over-expression of KGF mimic human middle ear cholesteatoma. AB - We reported previously that keratinocyte growth factor (KGF), a mesenchymal cell derived paracrine growth factor, plays an important role in middle ear cholesteatoma formation, which is characterized by marked proliferation of epithelial cells. Here, we investigated whether KGF, the main factor that induces cholesteatoma, overexpression in vivo results in the formation of cholesteatoma. Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal (EAC) of rats once (short-term model) or five times on every fourth day (long-term model). Ears transfected with empty vector were used as controls. Successful transfection of plasmids into epithelial and stromal cells was confirmed by Flag immunohistochemistry. In the short-term model, the intensity of KGF protein was the strongest in hKGF transfected ear at day 4. KGF expression induced epithelial cell proliferation, reaching a peak level at day 4 and then decreased later, while in the long-term model, KGF expression in the EAC led to middle ear cholesteatoma formation. In conclusion, we described here a new experimental model of human middle ear cholesteatoma, and demonstrated that KGF and KGF receptor paracrine action play an essential role in middle ear cholesteatoma formation in an in vivo model. PMID- 25138154 TI - Renegotiating cultural practices as a result of HIV in the eastern region of Malawi. AB - A number of studies have shown that HIV awareness is very high among Malawians and yet infection rates are rising. Local cultural practices have been identified as contributing to this contradictory situation. Using data from 12 focus-group discussions collected in Balaka, Zomba, Machinga and Mangochi, the paper explores the reformulation of nine cultural practices as a preventive measure against HIV. The study reveals that cultural practices that involve sexual acts for completion are mediated through condoms and HIV tests. The study also shows that traditional herbs known for healing ailments are repurposed to symbolise sexual acts. We conclude that the idea of repurposing offers an avenue in which initiation and cleansing rites that involve sexual acts are replaced by other semiotics such as a traditional medicine called mtela. We also conclude that the modifications to cultural practices do not indicate complete abandonment of associated traditions, rather, they constitute the renegotiation of cultural practices and meanings associated with particular rites of passage. Lastly, we propose that a comprehensive prevention programme needs to be part of a wider national HIV prevention effort combining a women and child rights and empowerment agenda and, critically, lifestyle lessons in a process of cultural renegotiation. PMID- 25138156 TI - First-hand sensory experience plays a limited role in children's early understanding of seeing and hearing as sources of knowledge: evidence from typically hearing and deaf children. AB - One early-developing component of theory of mind is an understanding of the link between sensory perception and knowledge formation. We know little about the extent to which children's first-hand sensory experiences drive the development of this understanding, as most tasks capturing this early understanding target vision, with less attention paid to the other senses. In this study, 64 typically hearing children (Mage = 4.0 years) and 21 orally educated deaf children (Mage = 5.44 years) were asked to identify which of two informants knew the identity of a toy animal when each had differing perceptual access to the animal. In the 'seeing' condition, one informant saw the animal and the other did not; in the 'hearing' condition, one informant heard the animal and the other did not. For both hearing and deaf children, there was no difference between performance on hearing and seeing trials, but deaf children were delayed in both conditions. Further, within both the hearing and deaf groups, older children outperformed younger children on these tasks, indicating that there is a developmental progression. Taken together, the pattern of results suggests that experiences other than first-hand sensory experiences drive children's developing understanding that sensory perception is associated with knowledge. PMID- 25138155 TI - Random variation in rectal position during radiotherapy for prostate cancer is two to three times greater than that predicted from prostate motion. AB - OBJECTIVE: Radiotherapy for prostate cancer does not explicitly take into account daily variation in the position of the rectum. It is important to accurately assess accumulated dose (DA) to the rectum in order to understand the relationship between dose and toxicity. The primary objective of this work was to quantify systematic (Sigma) and random (sigma) variation in the position of the rectum during a course of prostate radiotherapy. METHODS: The rectum was manually outlined on the kilo-voltage planning scan and 37 daily mega-voltage image guidance scans for 10 participants recruited to the VoxTox study. The femoral heads were used to produce a fixed point to which all rectal contours were referenced. RESULTS: Sigma [standard deviation (SD) of means] between planning and treatment was 4.2 mm in the anteroposterior (AP) direction and 1.3 mm left right (LR). sigma (root mean square of SDs) was 5.2 mm AP and 2.7 mm LR. Superior inferior variation was less than one slice above and below the planning position. CONCLUSION: Our results for Sigma are in line with published data for prostate motion. sigma, however, was approximately twice as great as that seen for prostate motion. This suggests that DA may differ from planned dose in some patients treated with radiotherapy for prostate cancer. ADVANCES IN KNOWLEDGE: This work is the first to use daily imaging to quantify Sigma and sigma of the rectum in prostate cancer. sigma was found to be greater than published data, providing strong rationale for further investigation of individual DA. PMID- 25138158 TI - The pathogenic mechanism of diabetes varies with the degree of overexpression and oligomerization of human amylin in the pancreatic islet beta cells. AB - The aggregation of human amylin (hA) to form cytotoxic structures has been closely associated with the causation of type 2 diabetes. We sought to advance understanding of how altered expression and aggregation of hA might link beta cell degeneration with diabetes onset and progression, by comparing phenotypes between homozygous and hemizygous hA-transgenic mice. The homozygous mice displayed elevated islet hA that correlated positively with measures of oligomer formation (r=0.91; P<0.0001). They also developed hyperinsulinemia with transient insulin resistance during the prediabetes stage and then underwent rapid beta cell loss, culminating in severe juvenile-onset diabetes. The prediabetes stage was prolonged in the hemizygous mice, wherein beta-cell dysfunction and extensive oligomer formation occurred in adulthood at a much later stage, when hA levels were lower (r=-0.60; P<0.0001). This is the first report to show that hA-evoked diabetes is associated with age, insulin resistance, progressive islet dysfunction, and beta-cell apoptosis, which interact variably to cause the different diabetes syndromes. The various levels of hA elevation cause different extents of oligomer formation in the disease stages, thus eliciting early- or adult-onset diabetes syndromes, reminiscent of type 1 and 2 diabetes, respectively. Thus, the hA-evoked diabetes phenotypes differ substantively according to degree of amylin overproduction. These findings are relevant to the understanding of the pathogenesis and the development of experimental therapeutics for diabetes. PMID- 25138159 TI - The CAP1/Prss8 catalytic triad is not involved in PAR2 activation and protease nexin-1 (PN-1) inhibition. AB - Serine proteases, serine protease inhibitors, and protease-activated receptors (PARs) are responsible for several human skin disorders characterized by impaired epidermal permeability barrier function, desquamation, and inflammation. In this study, we addressed the consequences of a catalytically dead serine protease on epidermal homeostasis, the activation of PAR2 and the inhibition by the serine protease inhibitor nexin-1. The catalytically inactive serine protease CAP1/Prss8, when ectopically expressed in the mouse, retained the ability to induce skin disorders as well as its catalytically active counterpart (75%, n=81). Moreover, this phenotype was completely normalized in a PAR2-null background, indicating that the effects mediated by the catalytically inactive CAP1/Prss8 depend on PAR2 (95%, n=131). Finally, nexin-1 displayed analogous inhibitory capacity on both wild-type and inactive mutant CAP1/Prss8 in vitro and in vivo (64% n=151 vs. 89% n=109, respectively), indicating that the catalytic site of CAP1/Prss8 is dispensable for nexin-1 inhibition. Our results demonstrate a novel inhibitory interaction between CAP1/Prss8 and nexin-1, opening the search for specific CAP1/Prss8 antagonists that are independent of its catalytic activity. PMID- 25138160 TI - Sumanenyl metallocenes: synthesis and structure of mono- and trinuclear zirconocene complexes. AB - Mono- and trinuclear sumanenyl zirconocene complexes Cp(sumanenyl)ZrCl2, Cp*(sumanenyl)ZrCl2, and (C21H9)[(Cp*)ZrCl2]3 were successfully synthesized. In the mononuclear complexes, convex binding with disturbed eta(5)-bonding was confirmed in a solid state. As demonstrated in the trinuclear complex, the multibenzylic anion of sumanene offers a novel ligand for the multinuclear metallocenes. PMID- 25138157 TI - Melanoma upregulates ICAM-1 expression on endothelial cells through engagement of tumor CD44 with endothelial E-selectin and activation of a PKCalpha-p38-SP-1 pathway. AB - Cancer metastasis involves multistep adhesive interactions between tumor cells (TCs) and endothelial cells (ECs), but the molecular mechanisms of intercellular communication in the tumor microenvironment remain elusive. Using static and flow coculture systems in conjunction with flow cytometry, we discovered that certain receptors on the ECs are upregulated on melanoma cell adhesion. Direct contact but not separate coculture between human umbilical endothelial cells (HUVECs) and a human melanoma cell line (Lu1205) increased intercellular adhesion molecule 1 (ICAM-1) and E-selectin expression on HUVECs by 3- and 1.5-fold, respectively, compared with HUVECs alone. The nonmetastatic cell line WM35 failed to promote ICAM-1 expression changes in HUVECs on contact. Enzyme-linked immunosorbent assay (ELISA) revealed that EC-TC contact has a synergistic effect on the expression of the cytokines interleukin (IL)-8, IL-6, and growth-related oncogene alpha (Gro alpha). By using E-selectin cross-linking and beads coated with CD44 immunopurified from Lu1205 cells, we showed that CD44/selectin ligation was responsible for the ICAM-1 up-regulation on HUVECs. Protein kinase Calpha (PKC alpha) activation was found to be the downstream target of the CD44/selectin initiated signaling, as ICAM-1 elevation was inhibited by siRNA targeting PKCalpha or a dominant negative form of PKCalpha (PKCalpha DN). Western blot analysis and electrophoretic mobility shift assays (EMSAs) showed that TC-EC contact mediated p38 phosphorylation and binding of the transcription factor SP-1 to its regulation site. In conclusion, CD44/selectin binding signals ICAM-1 up regulation on the EC surface through a PKCalpha-p38-SP-1 pathway, which further enhances melanoma cell adhesion to ECs during metastasis. PMID- 25138161 TI - Identification of essential histidine residues involved in heme binding and Hemozoin formation in heme detoxification protein from Plasmodium falciparum. AB - Malaria parasites digest hemoglobin within a food vacuole to supply amino acids, releasing the toxic product heme. During the detoxification, toxic free heme is converted into an insoluble crystalline form called hemozoin (Hz). Heme detoxification protein (HDP) in Plasmodium falciparum is one of the most potent of the hemozoin-producing enzymes. However, the reaction mechanisms of HDP are poorly understood. We identified the active site residues in HDP using a combination of Hz formation assay and spectroscopic characterization of mutant proteins. Replacement of the critical histidine residues His122, His172, His175, and His197 resulted in a reduction in the Hz formation activity to approximately 50% of the wild-type protein. Spectroscopic characterization of histidine substituted mutants revealed that His122 binds heme and that His172 and His175 form a part of another heme-binding site. Our results show that the histidine residues could be present in the individual active sites and could be ligated to each heme. The interaction between heme and the histidine residues would serve as a molecular tether, allowing the proper positioning of two hemes to enable heme dimer formation. The heme dimer would act as a seed for the crystal growth of Hz in P. falciparum. PMID- 25138162 TI - The cost-effectiveness of infliximab in Crohn's disease. AB - Crohn's disease (CD) is a chronic inflammatory condition that can affect any part of the gastrointestinal tract. It leads to severe symptoms and reduced quality of life. Infliximab is a monoclonal antibody against TNF-alpha and is effective in treating moderate to severe CD. It is associated with high treatment costs, but subsequent reductions in hospitalisation and surgery have been reported. This review examines the evidence for the cost-effectiveness of infliximab for the treatment of CD. Studies have been found to be very heterogeneous depending on setting, costs assumed and clinical data. Within the UK setting infliximab has been found to be cost effective with increased costs of around L25,000 per quality adjusted life year gained. PMID- 25138163 TI - Arterial pressure and flow wave analysis using time-domain 1-D hemodynamics. AB - We reviewed existing methods for analyzing, in the time domain, physical mechanisms underlying the patterns of blood pressure and flow waveforms in the arterial system. These are wave intensity analysis and separations into several types of waveforms: (i) forward- and backward-traveling, (ii) peripheral and conduit, or (iii) reservoir and excess. We assessed the physical information provided by each method and showed how to combine existing methods in order to quantify contributions to numerically generated waveforms from previous cardiac cycles and from specific regions and properties of the numerical domain: the aortic root, arterial bifurcations and tapered vessels, peripheral reflection sites, and the Windkessel function of the aorta. We illustrated our results with numerical examples involving generalized arterial stiffening in a distributed one dimensional model or localized changes in the model parameters due to a femoral stenosis, carotid stent or abdominal aortic aneurysm. PMID- 25138164 TI - Design and validation of a novel ferromagnetic bare metal stent capable of capturing and retaining endothelial cells. AB - Rapid healing of vascular stents is important for avoiding complications associated with stent thrombosis, restenosis, and bleeding related to antiplatelet drugs. Magnetic forces can be used to capture iron-labeled endothelial cells immediately following stent implantation, thereby promoting healing. This strategy requires the development of a magnetic stent that is biocompatible and functional. We designed a stent from the weakly ferromagnetic 2205 stainless steel using finite element analysis. The final design exhibited a principal strain below the fracture limit of 30% during crimping and expansion. Ten stents were fabricated and validated experimentally for fracture resistance. Another 10 stents magnetized with a neodymium magnet showed a magnetic field in the range of 100-750 mG. The retained magnetism was sufficiently strong to capture magnetically-labeled endothelial cells on the stent surfaces during in vitro studies. Magnetically-labeled endothelial cell capture was also verified in vivo after 7 days following coronary implantation in 4 pigs using histological analysis. Images of the stented blood vessels showed uniform endothelium formation on the stent surfaces. In conclusion, we have designed a ferromagnetic bare metal stent from 2205 stainless steel that is functional, biocompatible, and able to capture and retain magnetically-labeled endothelial cells in order to promote rapid stent healing. PMID- 25138166 TI - Improved amorphous/crystalline silicon interface passivation for heterojunction solar cells by low-temperature chemical vapor deposition and post-annealing treatment. AB - In this study, hydrogenated amorphous silicon (a-Si:H) thin films are deposited using a radio-frequency plasma-enhanced chemical vapor deposition (RF-PECVD) system. The Si-H configuration of the a-Si:H/c-Si interface is regulated by optimizing the deposition temperature and post-annealing duration to improve the minority carrier lifetime (taueff) of a commercial Czochralski (Cz) silicon wafer. The mechanism of this improvement involves saturation of the microstructural defects with hydrogen evolved within the a-Si:H films due to the transformation from SiH2 into SiH during the annealing process. The post annealing temperature is controlled to ~180 degrees C so that silicon heterojunction solar cells (SHJ) could be prepared without an additional annealing step. To achieve better performance of the SHJ solar cells, we also optimize the thickness of the a-Si:H passivation layer. Finally, complete SHJ solar cells are fabricated using different temperatures for the a-Si:H film deposition to study the influence of the deposition temperature on the solar cell parameters. For the optimized a-Si:H deposition conditions, an efficiency of 18.41% is achieved on a textured Cz silicon wafer. PMID- 25138165 TI - Change of direction in the biomechanics of atherosclerosis. AB - The non-uniform distribution of atherosclerosis within the arterial system has been attributed to pro-atherogenic influences of low, oscillatory haemodynamic wall shear stress (WSS) on endothelial cells (EC). This theory is challenged by the changes in lesion location that occur with age in human and rabbit aortas. Furthermore, a number of point-wise comparisons of lesion prevalence and WSS have failed to support it. Here we investigate the hypothesis that multidirectional flow-characterized as the average magnitude of WSS components acting transversely to the mean vector (transWSS)-plays a key role. Maps of lesion prevalence around aortic branch ostia in immature and mature rabbits were compared with equivalent maps of time average WSS, the OSI (an index characterizing oscillatory flow) and transWSS, obtained from computational simulations; Spearman's rank correlation coefficients were calculated for aggregated data and 95% confidence intervals were obtained by bootstrapping methods. Lesion prevalence correlated positively, strongly and significantly with transWSS at both ages. Correlations of lesion prevalence with the other shear metrics were not significant or were significantly lower than those obtained for transWSS. No correlation supported the low, oscillatory WSS theory. The data are consistent with the view that multidirectional near-wall flow is highly pro-atherogenic. Effects of multidirectional flow on EC, and methods for investigating them, are reviewed. The finding that oscillatory flow has pro-inflammatory effects when acting perpendicularly to the long axis of EC but anti-inflammatory effects when acting parallel to it may explain the stronger correlation of lesion prevalence with transWSS than with the OSI. PMID- 25138167 TI - Absence of amplification of the FGFR1-gene in human malignant mesothelioma of the pleura: a pilot study. AB - BACKGROUND: Mesothelioma (MPM) is a rare malignant disease with a worse outcome. Fibroblast growth factor 1 (FGFR1) may be an interesting target for selective tyrosine kinases inhibitors (TKI) in MPM. The aim of this study was to evaluate the amplification of the FGFR1 gene in patients suffering from MPM. FINDINGS: We identified nineteen male patients treated in our department between August 2008 and July 2010 matching the inclusion criteria. Mean age was 68 years. Histopathological examination confirmed thirteen patients with epitheloid subtype, five with biphasic and one patient with sarcomatoid. Fluorescence in situ hybridization analysis revealed no polysomy nor an amplification of the FGFR gene copy number in any case. CONCLUSION: Regarding that also EGFR amplifications in MPM are absolute rarities, our findings may be a hint that TKI's will not satisfy the hope for a new era in the treatment of MPM. PMID- 25138168 TI - Comparative assembly hubs: web-accessible browsers for comparative genomics. AB - MOTIVATION: Researchers now have access to large volumes of genome sequences for comparative analysis, some generated by the plethora of public sequencing projects and, increasingly, from individual efforts. It is not possible, or necessarily desirable, that the public genome browsers attempt to curate all these data. Instead, a wealth of powerful tools is emerging to empower users to create their own visualizations and browsers. RESULTS: We introduce a pipeline to easily generate collections of Web-accessible UCSC Genome Browsers interrelated by an alignment. It is intended to democratize our comparative genomic browser resources, serving the broad and growing community of evolutionary genomicists and facilitating easy public sharing via the Internet. Using the alignment, all annotations and the alignment itself can be efficiently viewed with reference to any genome in the collection, symmetrically. A new, intelligently scaled alignment display makes it simple to view all changes between the genomes at all levels of resolution, from substitutions to complex structural rearrangements, including duplications. To demonstrate this work, we create a comparative assembly hub containing 57 Escherichia coli and 9 Shigella genomes and show examples that highlight their unique biology. AVAILABILITY AND IMPLEMENTATION: The source code is available as open source at: https://github.com/glennhickey/progressiveCactus The E.coli and Shigella genome hub is now a public hub listed on the UCSC browser public hubs Web page. PMID- 25138169 TI - Pepper: cytoscape app for protein complex expansion using protein-protein interaction networks. AB - We introduce Pepper (Protein complex Expansion using Protein-Protein intERactions), a Cytoscape app designed to identify protein complexes as densely connected subnetworks from seed lists of proteins derived from proteomic studies. Pepper identifies connected subgraph by using multi-objective optimization involving two functions: (i) the coverage, a solution must contain as many proteins from the seed as possible, (ii) the density, the proteins of a solution must be as connected as possible, using only interactions from a proteome-wide interaction network. Comparisons based on gold standard yeast and human datasets showed Pepper's integrative approach as superior to standard protein complex discovery methods. The visualization and interpretation of the results are facilitated by an automated post-processing pipeline based on topological analysis and data integration about the predicted complex proteins. Pepper is a user-friendly tool that can be used to analyse any list of proteins. AVAILABILITY: Pepper is available from the Cytoscape plug-in manager or online (http://apps.cytoscape.org/apps/pepper) and released under GNU General Public License version 3. PMID- 25138170 TI - The difficulty in evaluating all findings in study on use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis. PMID- 25138171 TI - Pertuzumab in combination with trastuzumab and docetaxel for the treatment of HER2-positive metastatic or locally recurrent unresectable breast cancer. AB - The National Institute for Health and Care Excellence (NICE) invited the manufacturer of pertuzumab (Roche) to submit evidence for the clinical and cost effectiveness of pertuzumab + trastuzumab + docetaxel for the treatment of human epidermal growth factor receptor 2-positive (HER2+) metastatic or locally recurrent unresectable breast cancer in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarises the ERG's review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee's (AC) initial decision. At the time of writing, final guidance had not been published by NICE. The clinical evidence was mainly derived from an ongoing phase III randomised double-blind placebo-controlled international multicentre clinical trial (CLEOPATRA), designed to evaluate efficacy and safety in 808 patients, which compared pertuzumab + trastuzumab + docetaxel (pertuzumab arm) with placebo + trastuzumab + docetaxel (control arm). Both progression-free survival (PFS) and overall survival (OS) were analysed at two data cut-off points May 2011 (median follow-up of 18 months) and May 2012 (median follow-up of 30 months). At both time points, PFS was significantly longer in the pertuzumab arm (18.5 months compared with 12.4 months in the control arm at the first data cut off point and 18.7 versus 12.4 months at the second data cut-off point). Assessment of OS benefit suggested an improvement for patients in the pertuzumab arm with a strong trend towards an OS benefit at the second data cut-off point; however, due to the immaturity of the OS data, the magnitude of the OS benefit was uncertain. Importantly, cardiotoxicity was not increased in patients treated with a combination of pertuzumab + trastuzumab + docetaxel. The ERG's main concern with the clinical effectiveness data was the lack of mature OS data. An additional concern of the AC was that the majority of patients in the randomised controlled trial were trastuzumab naive, which does not reflect current clinical practice. The incremental cost-effectiveness ratios (ICERs) generated by the manufacturer's model are considered to be commercial in confidence data and therefore cannot be published. Nevertheless, the results of the manufacturer's probabilistic sensitivity analyses suggest that pertuzumab + trastuzumab + docetaxel has a 0 % probability of being cost effective at a willingness-to-pay of L30,000 per quality-adjusted life-year gained when compared with trastuzumab + docetaxel. The ERG believes that more realistic estimates of the ICERs are considerably higher, almost double those presented by the manufacturer. This is because the ERG believes that due to the manner in which the economic model is constructed, the additional survival benefit following disease progression that is generated for patients treated with pemetrexed + trastuzumab + docetaxel is unrealistic. At the time of writing, NICE had not made a final decision regarding this technology but had instead referred the issue of the assessment of technologies that are not effective at a zero price to their Decision Support Unit for advice. PMID- 25138172 TI - Associations of socioeconomic position and pain prevalence in the United States: findings from the National Health and Nutrition Examination Survey. AB - BACKGROUND: Pain is a significant burden within the U.S. adult population, but little is known regarding epidemiology of pain, particularly with respect to race, ethnicity, and socioeconomic position (SEP). OBJECTIVE: The purpose of this study was to describe and evaluate prevalence and distribution of pain in the United States. METHODS: With data from the population-based 2003-2004 National Health and Nutrition Examination Survey, prevalence of acute (<3 months) and chronic (>= 3 months) pain was evaluated, including subgroup analyses of race, ethnicity, and SEP, with SEP defined by the poverty-to-income ratio, a ratio derived from the federal poverty level, accounting for household income and number of household members. RESULTS: Prevalence of acute pain was 12.2% (95% confidence interval: 11.2-13.3%). Non-Hispanic black as well as Hispanic and Mexican-American individuals had higher rates of acute pain than non-Hispanic white people, and a higher prevalence was noted in those with higher SEP. Chronic pain prevalence was 15.6% (13.4-17.7%), with non-Hispanic white people having a higher prevalence than those in other racial and ethnic groups. CONCLUSION: Trends of chronic pain by SEP were opposite of acute pain as those in the highest SEP group tended to have less chronic pain than those in lower SEP groups. These findings suggest that SEP, in addition to race and ethnicity, may play a role in the development of pain as well as its treatment and management. PMID- 25138173 TI - Deferasirox for iron chelation in multitransfused children with sickle cell disease; long-term experience in the East London clinical haemoglobinopathy network. AB - Deferasirox (DFX) has been licensed for iron chelation in patients with sickle cell disease (SCD), but there is limited data on its long-term efficacy and safety in children. This retrospective study included 62 regularly transfused children managed in the East London and Essex Clinical Haemoglobinopathy Network (mean age 9.2 +/- 3.2 yr). Efficacy measurements consisted of monthly serum ferritin (SF) and annual R2 MRI-estimated liver iron concentration (LIC), and safety markers included serum creatinine and alanine aminotransferase (ALT). The mean duration of DFX treatment was 2.5 +/- 1.4 yr, and mean dose at 36 months was 25 mg/kg/d. Mean SF at initiation of treatment was 2542 +/- 952 ng/mL and increased to 4691 +/- 2255 ng/mL at 36 months (P = 0.05). Mean LIC on first scan was 10.3 mg/g dry weight and did not decrease significantly on follow-up scans. There was a significant correlation between relative change in LIC and in SF (R(2) = 0.66, P < 0.001). Reversible transaminitis episodes, probably due to drug induced hepatitis, were noted in 53% of patients. Responses to an adherence and acceptability questionnaire indicated that more than 50% of children had difficulties in taking DFX, commonly because of unpleasant taste. Our results show that more than 50% of children with SCD have inadequate control of iron overload with DFX. It is not clear whether this is because of frequent dose interruptions, poor tolerability and adherence, or poor efficacy of the drug. We recommend further studies to confirm these findings and to optimise iron chelation in this population. PMID- 25138174 TI - Do mixotrophs grow as photoheterotrophs? Photophysiological acclimation of the chrysophyte Ochromonas danica after feeding. AB - Mixotrophy is increasingly recognized as an important and widespread nutritional strategy in various taxonomic groups ranging from protists to higher plants. We hypothesize that the availability of alternative carbon and energy sources during mixotrophy allows a switch to photoheterotrophic growth, where the photosynthetic apparatus mainly provides energy but not fixed carbon. Because such a change in the function of the photosynthetic machinery is probably reflected in its composition, we compared the photosynthetic machinery in Ochromonas danica during autotrophic and mixotrophic growth. Compared with autotrophic growth, the total pigmentation of O. danica was reduced during mixotrophic growth. Furthermore, the photosystem I (PSI):PSII ratio increased, and the cellular content of Rubisco decreased not only absolutely, but also relative to the content of PSII. The changing composition of the photosynthetic apparatus indicates a shift in its function from providing both carbon and energy during photoautotrophy to mainly providing energy during mixotrophy. This preference for photoheterotrophic growth has interesting implications for the contribution of mixotrophic species to carbon cycling in diverse ecosystems. PMID- 25138175 TI - Potentiation of the in vitro antistaphylococcal effect of oxacillin and tetracycline by the anti-inflammatory drug diacetyl rhein. AB - BACKGROUND: The anti-inflammatory drug diacetyl rhein has been found to possess promising antistaphylococcal effects against various drug-resistant strains in our previous study. In the present work, we explored the in vitro combinatory interactions of diacetyl rhein with oxacillin and tetracycline against 13 standard strains and clinical isolates of Staphylococcus aureus, including those resistant to erythromycin, methicillin and tetracycline. METHODS: Minimum inhibitory concentrations were determined by broth microdilution assay, and the effects of combinations were evaluated according to the sum of fractional inhibitory concentrations (SigmaFICs). RESULTS: Synergistic or additive effects were observed against all S. aureus strains (SigmaFIC 0.258-1), whereas diacetyl rhein-oxacillin appeared to be the most effective combination, synergistically inhibiting the growth of 4 strains tested. CONCLUSION: To our best knowledge, this is the first report on a synergistic antibacterial effect of diacetyl rhein. Our results suggest this promising compound for further evaluation of its synergistic anti-infective potential as an agent with a combined anti inflammatory and synergistic antibacterial action. PMID- 25138176 TI - CYP-13A12 of the nematode Caenorhabditis elegans is a PUFA-epoxygenase involved in behavioural response to reoxygenation. AB - A specific behavioural response of Caenorhabditis elegans, the rapid increase of locomotion in response to anoxia/reoxygenation called the O2-ON response, has been used to model key aspects of ischaemia/reperfusion injury. A genetic suppressor screen demonstrated a direct causal role of CYP (cytochrome P450) 13A12 in this response and suggested that CYP-eicosanoids, which in mammals influence the contractility of cardiomyocytes and vascular smooth muscle cells, might function in C. elegans as specific regulators of the body muscle cell activity. In the present study we show that co-expression of CYP-13A12 with the NADPH-CYP-reductase EMB-8 in insect cells resulted in the reconstitution of an active microsomal mono-oxygenase system that metabolized EPA (eicosapentaenoic acid) and also AA (arachidonic acid) to specific sets of regioisomeric epoxy and hydroxy derivatives. The main products included 17,18-EEQ (17,18 epoxyeicosatetraenoic acid) from EPA and 14,15-EET (14,15-epoxyeicosatrienoic acid) from AA. Locomotion assays showed that the defective O2-ON response of C20 PUFA (polyunsaturated fatty acid)-deficient, Delta-12 and Delta-6 fatty acid desaturase mutants (fat-2 and fat-3 respectively) can be restored by feeding the nematodes AA or EPA, but not ETYA (eicosatetraynoic acid), a non-metabolizable AA analogue. Short-term incubation with 17,18-EEQ was sufficient to rescue the impaired locomotion of the fat-3 strain. The endogenous level of free 17,18-EEQ declined during anoxia and was rapidly restored in response to reoxygenation. On the basis of these results, we suggest that CYP-dependent eicosanoids such as 17,18-EEQ function as signalling molecules in the regulation of the O2-ON response in C. elegans. Remarkably, the exogenously administered 17,18-EEQ increased the locomotion activity under normoxic conditions and was effective not only with C20-PUFA-deficient mutants, but to a lesser extent also with wild-type worms. PMID- 25138177 TI - Innovations: resetting our thinking to solve problems. PMID- 25138178 TI - SEDUCEd by optical coherence tomography in drug-eluting balloon assessment. PMID- 25138179 TI - Lessons from acute and late scaffold failures in the ABSORB EXTEND trial: have we really learned them all? PMID- 25138180 TI - Emerging strategies for rapid reversal of anticoagulation in patients undergoing catheter-based interventions: aptamers enter the RADAR. PMID- 25138182 TI - Optical coherence tomography study of healing characteristics of paclitaxel eluting balloons vs. everolimus-eluting stents for in-stent restenosis: the SEDUCE (Safety and Efficacy of a Drug elUting balloon in Coronary artery rEstenosis) randomised clinical trial. AB - AIMS: Little is known about the respective healing responses and clinical efficacy and safety of drug-eluting balloons (DEB) and the second generation of drug-eluting stents (DES) when used to treat in-stent restenosis (ISR). In this study, we set out to compare prospectively the healing characteristics, as assessed by optical coherence tomography (OCT), of DEB versus DES after treatment of ISR in bare metal stents (BMS). METHODS AND RESULTS: Fifty patients with BMS ISR were randomised to treatment with a paclitaxel-eluting balloon vs. an everolimus-eluting stent (EES). The primary endpoint was the percentage of uncovered struts, assessed with OCT at nine months, as a marker of vessel wall healing. A mean of 366+/-135 and 636+/-184 struts were analysed per patient in the DEB and EES groups, respectively. The percentage of uncovered struts per patient was significantly lower with DEB vs. EES (1.4% vs. 3.1%, p=0.025). Mean neointimal hyperplasia area was 2.4+/-1.08 mm in DEB vs. 1.92+/-0.67 mm in EES (p=0.1806), while the percentage of malapposed struts per patient was very low in both groups (0.2% vs. 0.3%, p=0.699). At nine months, angiographic in-stent MLD (minimum lumen diameter) was lower (2.13 vs. 2.54 mm, p=0.006), while diameter stenosis (26.4 vs. 11.4%, p=0.002), and LLL (0.28 vs. 0.07 mm, p=0.1) were higher after DEB compared to EES. During one-year follow-up, we did not observe differences in the rates of death, TLR (target lesion revascularisation) or stent thrombosis. CONCLUSIONS: DEB appears to be associated with better healing characteristics, as assessed by stent strut coverage with OCT, but tended to be slightly less effective compared to EES. These findings give support to the use of either DEB or EES as valuable treatment options for ISR. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT 01065532. PMID- 25138183 TI - Comparison of bivalirudin and heparin in patients undergoing rotational atherectomy: a subanalysis of the randomised ROTAXUS trial. AB - AIMS: Bivalirudin has emerged as a meaningful alternative to heparin in patients undergoing percutaneous coronary intervention (PCI). To date, it is unclear whether bivalirudin has advantages in patients undergoing rotational atherectomy (RA). METHODS AND RESULTS: The current subgroup analysis of the ROTAXUS trial compared patients receiving bivalirudin (n=129) to those receiving unfractionated heparin (UFH) (n=111). Efficacy was assessed by the frequency of periprocedural myocardial infarction (MI) and safety by the frequency of major access-site bleeding (ASB). Baseline characteristics were similar. Periprocedural MI occurred less frequently in the bivalirudin group (22% vs. 37.5%, p=0.02), while ASB did not differ significantly (2.3% vs. 5.5%, p=0.20). This effect was larger in the RA group, where bivalirudin significantly reduced periprocedural MI (15.7% vs. 38.7%, p=0.01) with a trend towards reduced major ASB (2.9% vs. 10.2%, p=0.09). In the control group without RA, bivalirudin was not superior to UFH regarding periprocedural MI (28.6% vs. 36.6%, p=0.42) and major ASB (1.7% vs. 1.7%, p=0.99). CONCLUSIONS: This analysis suggests a differential benefit of bivalirudin in patients treated with RA. Patients receiving bivalirudin during RA showed significantly less periprocedural MI and fewer ASB compared to patients treated with UFH. PMID- 25138184 TI - ST peak during percutaneous coronary intervention serves as an early prognostic predictor in patients with ST-segment elevation myocardial. AB - AIMS: To evaluate the clinical importance of the ST peak phenomenon during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: Continuous ST monitoring was performed in 942 STEMI patients from arrival until 90 minutes after revascularisation. ST peak was defined as >=1 mm increase in the ST-segment during PCI compared with the ST elevation before intervention. ST peak was observed in 26.9% of patients. During median follow-up of 4.1 years, 20.7% of patients experienced a major adverse cardiac event (MACE). ST peak was associated with higher rates of mortality (13.4% versus 9.3%; p=0.044), admission for heart failure (10.6% versus 5.2%; p=0.002) and MACE (26.9% versus 18.2%; p=0.002), but not reinfarction (7.1% versus 5.2%; p=0.14). In two different Cox regression analyses, adjusting for predictors of MACE and ST peak including ST resolution and epicardial flow, ST peak remained significantly associated with MACE: adjusted hazard ratio (HR) 1.40 (95% confidence interval [CI] 1.01-1.95) and 1.41 (95% CI: 1.02-1.96). CONCLUSIONS: In the largest study hitherto evaluating the ST peak phenomenon during primary PCI, we demonstrated that ST peak is a strong predictor of adverse long-term outcome and provides independent prognostic information beyond that provided by ST resolution and epicardial flow. PMID- 25138185 TI - Serial intravascular ultrasound observations from the Tryton first-in-man study. AB - AIMS: To report serial intravascular ultrasound (IVUS) findings of bifurcation lesions treated with the dedicated Tryton Side Branch Stent to assess mechanisms of restenosis. METHODS AND RESULTS: The Tryton FIM study was a multicentre, prospective, single-arm, "first-in-man" study to treat de novo bifurcation lesions. Minimum lumen area (MLA) sites and overall volumes were analysed within main vessels and side branches. Overall, 27 main vessels and 22 side branches had paired baseline and follow-up IVUS. The post-intervention main vessel MLA decreased from 5.3 (4.1, 6.2) to 4.8 (3.4, 5.7) mm2 at follow-up, p=0.02, and the side branch MLA decreased from 3.5 (3.0, 3.8) to 2.5 (2.2, 3.2) mm2, p=0.0005. Stent area at the side branch did not change (mean stent area from 4.0 [3.3, 4.1] to 3.8 [3.4, 4.2] mm3/mm, p=0.95). Neointimal hyperplasia (NIH) net volume obstruction (%) measured 1.8% (0.5, 7.0) for the entire main vessel and 14.9% (2.3, 31.1) for the entire side branch stents. In both main vessel and side branches the decrease in lumen area correlated significantly with NIH. CONCLUSIONS: Serial IVUS analysis of a new side branch Tryton stent showed no chronic stent recoil. Side branch underexpansion was common and along with superimposed NIH contributed to the reduction in lumen dimensions at follow-up. PMID- 25138186 TI - A rare cause of transient ischaemic attack in a young man: cardiac papillary fibroelastoma. PMID- 25138187 TI - Left atrial appendage closure for stroke prevention in non-valvular atrial fibrillation: rationale, devices in clinical development and insights into implantation techniques. AB - AIMS: In patients with atrial fibrillation, a relevant stroke risk (CHA2DS2-VASc score >=2) and a relative or absolute contraindication for oral anticoagulation, catheter-based LAA occlusion is performed increasingly in Europe. The present article summarises the rationale, clinical data, devices, implantation techniques and follow-up drug regimens. METHODS AND RESULTS: European survey data on patients with atrial fibrillation support the need for non-pharmacological approaches for stroke prevention in patients with atrial fibrillation. A relevant bleeding risk remains with novel oral anticoagulants (NOACs), which are also dependent on drug compliance. Recent long-term data from the PROTECT-AF trial and the CAP registry regarding the WATCHMAN LAA occluder device suggest safety and efficacy. First registry data support the safety of two other CE-marked devices, the AMPLATZER Cardiac Plug (ACP) and the Coherex WaveCrest device, which have become available in Europe. Other LAA occlusion devices are in clinical development. CONCLUSIONS: Catheter-based LAA occlusion is now being developed further as an interventional approach for stroke prevention in patients with atrial fibrillation. Implantation techniques and devices are being improved, which will probably result in better procedural safety. Appropriate operator training is of major importance for this approach. PMID- 25138188 TI - Percutaneous closure of ruptured sinus of Valsalva aneurysm: results from a multicentre experience. AB - AIMS: To evaluate the safety and efficacy of percutaneous closure (PC) using modified double-disc ventricular septal defect (VSD) occluders in patients with ruptured sinus of Valsalva aneurysm (RSVA). METHODS AND RESULTS: Between 2005 and 2012, 25 patients were enrolled in our study for attempted PC. There were five patients (20%) with RSVA combined with VSD and two (8%) with aortic regurgitation (AR). The median age was 45 years (24-74 years). The QP/QS was 2.4+/-0.6 (1.6 4.0). The median diameter of lesions was 6 mm (4-8 mm) while the median size of occluders was 8 mm (6-12 mm). Twenty-three patients (92%) underwent PC successfully. Occluders were retrieved in two patients within one week. Trivial residual shunts developed in three and mild occluder-related AR occurred in five at discharge. During a median follow-up of 19 months (6-96 months) all trivial residual shunts vanished and mild occluder-related AR disappeared in four out of five patients. The proportion of patients in NYHA Class III/IV was reduced from 72% at baseline to 12% at the time of last follow-up (p<0.001). CONCLUSIONS: In selected patients with RSVA, PC using modified double-disc occluders may become a valuable alternative to surgery with encouraging immediate outcomes and midterm results. PMID- 25138189 TI - Distal embolisation during carotid stenting is predicted by circulating levels of LDL cholesterol and C-reactive protein. AB - AIMS: Distal embolisation during carotid artery stenting (CAS) is the main cause of cerebral complications; thus, the amount of embolisation occurring during CAS can be considered as a surrogate endpoint of cerebral complications. Our aim was to find patient characteristics which are associated with a higher risk of embolisation during CAS. METHODS AND RESULTS: From January to December 2010 all consecutive patients undergoing CAS with embolic protection at three medium- to high-volume Italian centres were prospectively enrolled in this multicentre study. After CAS, the embolic debris was classified by visual inspection into two groups: "scarce" (no debris or hardly visible debris), and "relevant" (visible embolic debris) embolisation. Two hundred and thirty-six consecutive patients (79% males, 32.7% symptomatic) were enrolled. Open cell stents were used in 52.7% of the patients, distal filters were employed in 85.5% and proximal protection in 14.5%. Procedural success was achieved in 100% of procedures. Relevant embolisation was observed in 16.1% of patients, including those who suffered all the periprocedural complications (4.2%). At multivariate statistical analysis, high circulating LDL cholesterol and C-reactive protein levels were the only factors associated with relevant embolisation. CONCLUSIONS: In this study, high circulating LDL cholesterol and C-reactive protein levels were associated with relevant embolisation after CAS, opening up the hypothesis that therapy with statins before elective CAS may reduce plaque embolisation and improve outcome. (EudraCT number: 016737-95). PMID- 25138190 TI - Balloon pulmonary angioplasty: an additional treatment option to improve the prognosis of patients with chronic thromboembolic pulmonary hypertension. AB - AIMS: To evaluate the efficacy and safety of balloon pulmonary angioplasty (BPA) in patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH) using the results of pulmonary endarterectomy (PEA) for operable patients as a reference, and annotate the role of BPA in the management of CTEPH. METHODS AND RESULTS: Data from 53 CTEPH patients were collected retrospectively. Twenty four operable patients underwent PEA, and 29 non-operable patients underwent BPA. Patients who underwent BPA showed improved mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output (39.4+/-6.9 to 21.3+/-5.6 mmHg, 763+/-308 to 284+/-128 dyn.s-1.cm-5, 3.47+/-0.80 to 4.26+/-1.15 L/min, respectively); patients who received PEA showed similar efficacy (44.4+/-11.0 to 21.6+/-6.7 mmHg, 781+/-278 to 258+/-125 dyn.s-1.cm-5, 3.35+/-1.11 to 4.44+/-1.58 L/min, respectively). The mortality rates of BPA and PEA patients were 3.4% and 8.3%, respectively. CONCLUSIONS: The efficacy and safety of BPA for non-operable cases were similar to those achieved using PEA for operable cases. BPA could be an additional treatment option for non-operable CTEPH patients, and most CTEPH patients can be satisfactorily treated by BPA or PEA. PMID- 25138191 TI - Tools & Techniques - statistics: non-inferiority trials. PMID- 25138192 TI - How should I treat an undeployed stent stuck in the proximal LAD? Going for another round... PMID- 25138193 TI - The use of radial access decreases the risk of vascular access-site-related complications at a patient level but is associated with an increased risk at a population level: the radial paradox. PMID- 25138194 TI - Phylogenetic analysis of barley WRKY proteins and characterization of HvWRKY1 and -2 as repressors of the pathogen-inducible gene HvGER4c. AB - The WRKY transcription factors belong to an evolutionarily conserved superprotein family predominantly present in the plant kingdom. WRKY proteins of barley are not yet fully annotated and most of them are not functionally characterized. We performed a genome-wide identification of WRKY members based on the recently accessible barley draft genome sequence and full-length cDNA datasets. As a result, 34 novel putative proteins have been identified which extend the existing list for barley WRKYs to 94. Phylogenetic analysis of the WRKY domains allowed ranking into three groups (I, II, III), with an expansion in group III in monocots. Two members of subgroup IIa, the wound and pathogen-inducible HvWRKY1 and HvWRKY2, are known as negative defense regulators. Here, we demonstrate that both transcription factors repress the activity of the powdery mildew-induced promoter of HvGER4c, a germin-like defense-related protein. The repression did not require the negative defense regulator MLO nor was it affected by the presence of the R protein MLA12. Moreover, the expression of the Arabidopsis ortholog AtWRKY40 in barley compromised basal resistance to powdery mildew, providing evidence for functional conservation of sequence-related WRKY proteins across monocots and dicots. PMID- 25138196 TI - Policy brief. Do unemployed women give birth to infants with higher rates of infant mortality and low birthweight? PMID- 25138197 TI - Does "Out of work" get into the womb? Exploring the relationship between unemployment and adverse birth outcomes. AB - This study uses Texas vital records from 1994 to 2003 to examine the relationship between self-reported maternal unemployment and birth outcomes, including birthweight and infant mortality. In the preferred specification, a sample containing 1,344, 605 sibling births to 604,649 mothers was used. Regression results indicated that within the same women, being unemployed was associated with lower average birthweights and higher rates of infant mortality than being engaged in market work, especially when unemployment preceded market work, and a range of hypothesized mediators did little to attenuate these relationships. Interaction models revealed that the poor average birth outcomes related to unemployment were driven by observations with at least one other indicator of health complication, such as presence of a medical risk factor. These results confirm that the relationship between unemployment and mother-child health varies across individuals, although further research is needed to understand the causal linkages connecting unemployment, health risks, and birth outcomes. PMID- 25138195 TI - Effectiveness of individual placement and support supported employment for young adults. AB - AIM: The individual placement and support (IPS) model of supported employment was first developed in community mental health centres for adults with severe mental illness. While IPS is an established evidence-based practice in this broad population, evidence on its effectiveness focused specifically on young adults has been limited. The current study aimed to address this gap. METHODS: To investigate the effects of IPS on young adults, the authors conducted a secondary analysis on a pooled sample of 109 unemployed young adults (under age 30) from four randomized controlled trials employing a common research protocol that included a standardized measurement battery and rigorous fidelity monitoring. Researchers assessed these participants over 18 months on nine competitive employment outcome measures. RESULTS: On all measures, the IPS group had significantly better employment outcomes. Overall, 40 (82%) of IPS participants obtained employment during follow-up compared with 25 (42%) of control participants, chi(2) = 17.9, P < .001. IPS participants averaged 25.0 weeks of employment, compared with 7.0 weeks for control participants, t = 4.50, P < .001. CONCLUSIONS: The current analysis supports a small number of previous studies in showing that IPS is highly effective in helping young adults with severe mental illness to attain competitive employment. When young adults acquire competitive jobs and initiate a path towards normal adult roles, they may avoid the cycle of disability and psychiatric patient roles that are demeaning and demoralizing. PMID- 25138199 TI - Stress proliferation across generations? Examining the relationship between parental incarceration and childhood health. AB - Stress proliferation theory suggests that parental incarceration may have deleterious intergenerational health consequences. In this study, I use data from the 2011-2012 National Survey of Children's Health (NSCH) to estimate the relationship between parental incarceration and children's fair or poor overall health, a range of physical and mental health conditions, activity limitations, and chronic school absence. Descriptive statistics show that children of incarcerated parents are a vulnerable population who experience disadvantages across an array of health outcomes. After adjusting for demographic, socioeconomic, and familial characteristics, I find that parental incarceration is independently associated with learning disabilities, attention deficit disorder and attention deficit hyperactivity disorder, behavioral or conduct problems, developmental delays, and speech or language problems. Taken together, results suggest that children's health disadvantages are an overlooked and unintended consequence of mass incarceration and that incarceration, given its unequal distribution across the population, may have implications for population level racial-ethnic and social class inequalities in children's health. PMID- 25138198 TI - Gender and reinforcing associations between socioeconomic disadvantage and body mass over the life course. AB - Using the 1957-1993 data from the Wisconsin Longitudinal Study, we explore reciprocal associations between socioeconomic status (SES) and body mass in the 1939 birth cohort of non-Hispanic white men and women. We integrate the fundamental cause theory, the gender relations theory, and the life course perspective to analyze gender differences in (a) the ways that early socioeconomic disadvantage launches bidirectional associations of body mass and SES and (b) the extent to which these mutually reinforcing effects generate socioeconomic disparities in midlife body mass. Using structural equation modeling, we find that socioeconomic disadvantage at age 18 is related to higher body mass index and a greater risk of obesity at age 54, and that this relationship is significantly stronger for women than men. Moreover, women are more adversely affected by two mechanisms underlying the focal association: the obesogenic effect of socioeconomic disadvantage and the SES-impeding effect of obesity. These patterns were also replicated in propensity score-matching models. We conclude that gender and SES act synergistically over the life course to shape reciprocal chains of two disadvantaged statuses: heavier body mass and lower SES. PMID- 25138201 TI - "I want you to save my kid!": Illness management strategies, access, and inequality at an elite university research hospital. AB - Using data drawn from interviews and observations with 18 families whose children were diagnosed with life-threatening, often rare diseases, I examine how families accessed and negotiated medical care at a top 10-ranked university research hospital. Access to highly specialized and technologically advanced care was essential in these critical cases. Combining analysis of these high-stakes cases with recent work highlighting the interactional dynamics of care delivery, I show how families followed different paths to elite care and used different illness management strategies throughout the treatment process depending on their ability to mobilize what Janet Shim terms cultural health capital. These diverging illness management strategies reproduced inequality even at the top of the U.S. healthcare system by allowing some families to secure microadvantages throughout the illness experience. These findings suggest a complex interplay between structures of care delivery and families' illness management strategies and point to the need for broader conceptualizations of healthcare advantages. PMID- 25138200 TI - How health conditions translate into self-ratings: a comparative study of older adults across Europe. AB - Using data from the Survey of Health, Ageing and Retirement in Europe, we examine how respondents translate morbidity and disability into self-rated health (SRH), how national populations differ in SRH, and how normative and person-specific reporting styles shape SRH. We construct proxy variables that allow us to specify cultural differences in reporting styles and individual differences in relative rating behavior. Using generalized logistic regression, we find that both of these dimensions of subjectivity are related to SRH; however, their inclusion does not significantly alter the connection between SRH and the set of disease and disability indicators. Further, country differences in SRH persist after controlling for all these factors. Our findings suggest that observed country differences in SRH reflect compositional differences, cultural differences in reporting styles, and perceptions of how health restricts typical activities. SRH also seems to capture underlying but unmeasured health differences across populations. PMID- 25138202 TI - Spillover effects of an uninsured population. AB - A lack of health insurance has long been associated with negative effects on individual and family health due to access barriers. However, we know little about how a lack of health insurance affects wider communities beyond health care. Based on in-depth interviews in two Los Angeles communities, we report how a lack of health insurance affects the functioning of religious institutions and schools from kindergarten to 12th grade. We find a negative spillover effect at the individual and institutional levels for schools experiencing greater absenteeism due to health insurance problems of pupils. However, we find that religious organizations are little affected by a lack of health insurance of adherents. Instead, churches offer health programs as a means to engage their communities. Besides documenting a negative and a positive spillover effect, we offer a conceptual framework for the qualitative study of health spillover effects and examine the policy implications of our findings. PMID- 25138203 TI - Influence of distinct asthma phenotypes on lung function following weight loss in the obese. AB - BACKGROUND AND OBJECTIVE: There appears to be two distinct clinical phenotypes of obese patients with asthma-those with early-onset asthma and high serum IgE (TH2 high), and those with late-onset asthma and low serum IgE (TH2-low). The aim of the present study was to determine in the two phenotypes of obese asthma the effect of weight loss on small airway function. METHODS: TH2-low (n = 8) and TH2 high (n = 5) obese asthmatics underwent methacholine challenge before and 12 months following bariatric surgery. Dose-response slopes as measures of sensitivity to airway closure and narrowing were measured as maximum % fall forced vital capacity (FVC) and forced expiratory volume in 1 s/FVC, respectively, divided by dose. Resting airway mechanics were measured by forced oscillation technique. RESULTS: Weight loss reduced sensitivity to airway closure in TH 2-low but not TH2-high obese asthmatics (pre-post mean change +/- 95% confidence interval: 1.8 +/- 0.8 doubling doses vs -0.3 +/- 1.7 doubling doses, P = 0.04). However, there was no effect of weight loss on the sensitivity to airway narrowing in either group (P = 0.8, TH2-low: 0.8 +/- 1.0 doubling doses, TH2 high: -1.1 +/- 2.5 doubling doses). In contrast, respiratory resistance (20 Hz) improved in TH2-high but not in TH2-low obese asthmatics (pre-post change median interquartile range: 1.5 (1.3-2.8) cmH2O/L/s vs 0.6 (-1.8-0.8) cmH2O/L/s, P = 0.03). CONCLUSIONS: TH2-low obese asthmatics appear to be characterized by increased small airway responsiveness and abnormalities in resting airway function that may persist following weight loss. However, this was not the case for TH2-high obese asthmatics, highlighting the complex interplay between IgE status and asthma pathophysiology in obesity. PMID- 25138207 TI - Hospice Comics: Representations of Patient and Family Experience of Illness and Death in Graphic Novels. AB - Non-fiction graphic novels about illness and death created by patients and their loved ones have much to teach all readers. However, the bond of empathy made possible in the comic form may have special lessons for healthcare providers who read these texts and are open to the insights they provide. PMID- 25138208 TI - Label-free detection of serum proteins using surface-enhanced Raman spectroscopy for colorectal cancer screening. AB - Surface-enhanced Raman scattering (SERS) spectra of serum proteins purified from human serum samples were employed to detect colorectal cancer. Acetic acid as a new aggregating agent was introduced to increase the magnitude of the SERS enhancement. High-quality SERS spectra of serum proteins were acquired from 103 cancer patients and 103 healthy volunteers. Tentative assignments of SERS bands reflect that some specific biomolecular contents and protein secondary structures change with colorectal cancer progression. Principal component analysis combined with linear discriminant analysis was used to assess the capability of this approach for identifying colorectal cancer, yielding diagnostic accuracies of 100% (sensitivity: 100%; specificity: 100%) based on albumin SERS spectroscopy and 99.5% (sensitivity: 100%; specificity: 99%) based on globulin SERS spectroscopy, respectively. A partial least squares (PLS) approach was introduced to develop diagnostic models. An albumin PLS model successfully predicted the unidentified subjects with a diagnostic accuracy of 93.5% (sensitivity: 95.6%; specificity: 91.3%) and the globulin PLS model gave a diagnostic accuracy of 93.5% (sensitivity: 91.3%; specificity: 95.6%). These results suggest that serum protein SERS spectroscopy can be a sensitive and clinically powerful means for colorectal cancer detection. PMID- 25138206 TI - Impact of medical and psychiatric multi-morbidity on mortality in diabetes: emerging evidence. AB - BACKGROUND: Multi-morbidity, or the presence of multiple chronic diseases, is a major problem in clinical care and is associated with worse outcomes. Additionally, the presence of mental health conditions, such as depression, anxiety, etc., has further negative impact on clinical outcomes. However, most health systems are generally configured for management of individual diseases instead of multi-morbidity. The study examined the prevalence and differential impact of medical and psychiatric multi-morbidity on risk of death in adults with diabetes. METHODS: A national cohort of 625,903 veterans with type 2 diabetes was created by linking multiple patient and administrative files from 2002 through 2006. The main outcome was time to death. Primary independent variables were numbers of medical and psychiatric comorbidities over the study period. Covariates included age, gender, race/ethnicity, marital status, area of residence, service connection, and geographic region. Cox regression was used to model the association between time to death and multi-morbidity adjusting for relevant covariates. RESULTS: Hypertension (78%) and depression (13%) were the most prevalent medical and psychiatric comorbidities, respectively; 23% had 3+ medical comorbidities, 3% had 2+ psychiatric comorbidities and 22% died. Among medical comorbidities, mortality risk was highest in those with congestive heart failure (hazard ratio, HR = 1.92; 95% CI 1.89-1.95), Lung disease (HR = 1.42; 95% CI 1.40-1.44) and cerebrovascular disease (HR = 1.39; 95% CI 1.37-1.40). Among psychiatric comorbidities, mortality risk was highest in those with substance abuse (HR = 1.50; 95% CI 1.46-1.54), psychoses (HR = 1.16; 95% CI 1.14-1.19) and depression (HR = 1.05; 95% CI 1.03-1.07). There was an interaction between medical and psychiatric comorbidity (p = 0.003) so stratified analyses were performed. HRs for effect of 3+ medical comorbidity (2.63, 2.66, 2.15) remained high across levels of psychiatric comorbidities (0, 1, 2+), respectively. HRs for effect of 2+ psychiatric comorbidity (1.69, 1.63, 1.42, 1.38) declined across levels of medical comorbidity (0, 1, 2, 3+), respectively. CONCLUSIONS: Medical and psychiatric multi-morbidity are significant predictors of mortality among older adults (veterans) with type 2 diabetes with a graded response as multimorbidity increases. PMID- 25138209 TI - Waveband selection of reagent-free determination for thalassemia screening indicators using Fourier transform infrared spectroscopy with attenuated total reflection. AB - A reagent-free determination method for the thalassemia screening indicators hemoglobin (Hb), mean corpuscular Hb (MCH), and mean corpuscular volume (MCV) was developed based on Fourier transform infrared spectrometers equipped with an attenuated total reflection accessory. A random and stability-dependent rigorous process of calibration, prediction, and validation was conducted. Appropriate wavebands were selected using the improved moving window partial least squares method with stability and equivalence. The obtained optimal wavebands were 1722 to 1504 cm-1 for Hb, 1653 to 901 cm-1 for MCH, and 1562 to 964 cm-1 for MCV. A model set equivalent to the optimal model was proposed for each indicator; the public waveband of Hb equivalent wavebands was 1717 to 1510 cm-1, and the public equivalent waveband for MCH and MCV was 1562 to 901 cm-1. All selected wavebands were within the MIR fingerprint region and achieved high validation effects. The sensitivity and specificity were 100.0% and 96.9% for the optimal wavebands and 100.0% and 95.3% for the equivalent wavebands, respectively. Thus, the spectral prediction was highly accurate for determining negative and positive for thalassemia screening. This technique is rapid and simple in comparison with conventional methods and is a promising tool for thalassemia screening in large populations. PMID- 25138204 TI - Immunotherapy using lipopolysaccharide-stimulated bone marrow-derived dendritic cells to treat experimental autoimmune encephalomyelitis. AB - Lipopolysaccharide (LPS) produced by Gram-negative bacteria induces tolerance and suppresses inflammatory responses in vivo; however, the mechanisms are poorly understood. In this study we show that LPS induces apoptosis of bone marrow derived dendritic cells (DCs) and modulates phenotypes of DCs. LPS treatment up regulates expression of tolerance-associated molecules such as CD205 and galectin 1, but down-regulates expression of Gr-1 and B220 on CD11c(+) DCs. Moreover, LPS treatment regulates the numbers of CD11c(+) CD8(+) , CD11c(+) CD11b(low) and CD11c(+) CD11b(hi) DCs, which perform different immune functions in vivo. Our data also demonstrated that intravenous transfer of LPS-treated DCs blocks experimental autoimmune encephalomyelitis (EAE) development and down-regulates expression of retinoic acid-related orphan receptor gamma t (ROR-gammat), interleukin (IL)-17A, IL-17F, IL-21, IL-22 and interferon (IFN)-gamma in myelin oligodendrocyte glycoprotein (MOG)-primed CD4(+) T cells in the peripheral environment. These results suggest that LPS-induced apoptotic DCs may lead to generation of tolerogenic DCs and suppress the activity of MOG-stimulated effector CD4(+) T cells, thus inhibiting the development of EAE in vivo. Our results imply a potential mechanism of LPS-induced tolerance mediated by DCs and the possible use of LPS-induced apoptotic DCs to treat autoimmune diseases such as multiple sclerosis. PMID- 25138210 TI - Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL before and repeatedly after CSF removal. AB - Pseudo-continuous arterial spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH. PMID- 25138212 TI - Oncologic validity of recipient vessel preservation in microvascular free-flap reconstruction. AB - OBJECTIVES: The use of free-flap reconstruction requires a more limited neck dissection to allow for microvascular anastomosis. This study seeks to determine the oncologic validity of cervical vessel preservation. MATERIALS AND METHODS: The current study is a prospective review of cervical vessel biopsies from patients undergoing resection of squamous cell carcinoma (SCCA) tumors of the head and neck with free tissue reconstruction. RESULTS: From June 2010 to March 2012, 227 recipient vessel biopsies were performed on 100 patients. Three of these patients had grossly abnormal vessels, with malignancy confirmed by frozen section analysis. One patient had a vessel positive for malignancy that was grossly normal but found to have SCCA on the final pathology. CONCLUSIONS: When the recipient vessel appears grossly suspicious, a frozen section biopsy and re resection should be considered. Recipient vessel trimmings should routinely be sent for permanent pathology since in rare cases, they can be involved by tumor, affecting the margin status, prognosis, and indications for adjuvant therapy. PMID- 25138213 TI - miR-326-histone deacetylase-3 feedback loop regulates the invasion and tumorigenic and angiogenic response to anti-cancer drugs. AB - Histone modification is known to be associated with multidrug resistance phenotypes. Cancer cell lines that are resistant or have been made resistant to anti-cancer drugs showed lower expression levels of histone deacetylase-3 (HDAC3), among the histone deacetylase(s), than cancer cell lines that were sensitive to anti-cancer drugs. Celastrol and Taxol decreased the expression of HDAC3 in cancer cell lines sensitive to anti-cancer drugs. HDAC3 negatively regulated the invasion, migration, and anchorage-independent growth of cancer cells. HDAC3 conferred sensitivity to anti-cancer drugs in vitro and in vivo. TargetScan analysis predicted miR-326 as a negative regulator of HDAC3. ChIP assays and luciferase assays showed a negative feedback loop between HDAC3 and miR-326. miR-326 decreased the apoptotic effect of anti-cancer drugs, and the miR 326 inhibitor increased the apoptotic effect of anti-cancer drugs. miR-326 enhanced the invasion and migration potential of cancer cells. The miR-326 inhibitor negatively regulated the tumorigenic, metastatic, and angiogenic potential of anti-cancer drug-resistant cancer cells. HDAC3 showed a positive feedback loop with miRNAs such as miR-200b, miR-217, and miR-335. miR-200b, miR 217, and miR-335 negatively regulated the expression of miR-326 and the invasion and migration potential of cancer cells while enhancing the apoptotic effect of anti-cancer drugs. TargetScan analysis predicted miR-200b and miR-217 as negative regulators of cancer-associated gene, a cancer/testis antigen, which is known to regulate the response to anti-cancer drugs. HDAC3 and miR-326 acted upstream of the cancer-associated gene. Thus, we show that the miR-326-HDAC3 feedback loop can be employed as a target for the development of anti-cancer therapeutics. PMID- 25138214 TI - Vesicle associated membrane protein 8 (VAMP8)-mediated zymogen granule exocytosis is dependent on endosomal trafficking via the constitutive-like secretory pathway. AB - Acinar cell zymogen granules (ZG) express 2 isoforms of the vesicle-associated membrane protein family (VAMP2 and -8) thought to regulate exocytosis. Expression of tetanus toxin to cleave VAMP2 in VAMP8 knock-out (-/-) acini confirmed that VAMP2 and -8 are the primary VAMPs for regulated exocytosis, each contributing ~50% of the response. Analysis of VAMP8(-/-) acini indicated that although stimulated secretion was significantly reduced, a compensatory increase in constitutive secretion maintained total secretion equivalent to wild type (WT). Using a perifusion system to follow secretion over time revealed VAMP2 mediates an early rapid phase peaking and falling within 2-3 min, whereas VAMP8 controls a second prolonged phase that peaks at 4 min and slowly declines over 20 min to support the protracted secretory response. VAMP8(-/-) acini show increased expression of the endosomal proteins Ti-VAMP7 (2-fold) and Rab11a (4-fold) and their redistribution from endosomes to ZGs. Expression of GDP-trapped Rab11a-S25N inhibited secretion exclusively from the VAMP8 but not the VAMP2 pathway. VAMP8( /-) acini also showed a >90% decrease in the early endosomal proteins Rab5/D52/EEA1, which control anterograde trafficking in the constitutive-like secretory pathway. In WT acini, short term (14-16 h) culture also results in a >90% decrease in Rab5/D52/EEA1 and a complete loss of the VAMP8 pathway, whereas VAMP2-secretion remains intact. Remarkably, rescue of Rab5/D52/EEA1 expression restored the VAMP8 pathway. Expressed D52 shows extensive colocalization with Rab11a and VAMP8 and partially copurifies with ZG fractions. These results indicate that robust trafficking within the constitutive-like secretory pathway is required for VAMP8- but not VAMP2-mediated ZG exocytosis. PMID- 25138215 TI - Transcriptional regulation of the intestinal nuclear bile acid farnesoid X receptor (FXR) by the caudal-related homeobox 2 (CDX2). AB - Farnesoid X receptor (FXR, NR1H4) is a bile acid-activated transcription factor that belongs to the nuclear receptor superfamily. It is highly expressed in the enterohepatic system, where it senses bile acid levels to consequently reduce their synthesis while inducing their detoxification. Bile acids are intestinal tumor promoters and their concentrations have to be tightly regulated. Indeed, reduced expression of FXR in the intestine increases colorectal cancer susceptibility in mice, whereas its activation can promote apoptosis in genetically modified cells. Notably, despite the broad knowledge of the FXR enterohepatic transcriptional activity, the molecular mechanisms regulating FXR expression in the intestine are still unknown. Herein, by combining both gain and loss of function approaches and FXR promoter activity studies, we identified caudal-related homeobox 2 (CDX2) transcription factor as a positive regulator of FXR expression in the enterocytes. Our results provide a putative novel tool for modulating FXR expression against bile acid-related colorectal cancer progression. PMID- 25138211 TI - Targeting TRP channels for novel migraine therapeutics. AB - Migraine is increasingly understood to be a disorder of the brain. In susceptible individuals, a variety of "triggers" may influence altered central excitability, resulting in the activation and sensitization of trigeminal nociceptive afferents surrounding blood vessels (i.e., the trigeminovascular system), leading to migraine pain. Transient receptor potential (TRP) channels are expressed in a subset of dural afferents, including those containing calcitonin gene related peptide (CGRP). Activation of TRP channels promotes excitation of nociceptive afferent fibers and potentially lead to pain. In addition to pain, allodynia to mechanical and cold stimuli can result from sensitization of both peripheral afferents and of central pain pathways. TRP channels respond to a variety of endogenous conditions including chemical mediators and low pH. These channels can be activated by exogenous stimuli including a wide range of chemical and environmental irritants, some of which have been demonstrated to trigger migraine in humans. Activation of TRP channels can elicit CGRP release, and blocking the effects of CGRP through receptor antagonism or antibody strategies has been demonstrated to be effective in the treatment of migraine. Identification of approaches that can prevent activation of TRP channels provides an additional novel strategy for discovery of migraine therapeutics. PMID- 25138216 TI - Regression of replication forks stalled by leading-strand template damage: I. Both RecG and RuvAB catalyze regression, but RuvC cleaves the holliday junctions formed by RecG preferentially. AB - The orderly progression of replication forks formed at the origin of replication in Escherichia coli is challenged by encounters with template damage, slow moving RNA polymerases, and frozen DNA-protein complexes that stall the fork. These stalled forks are foci for genomic instability and must be reactivated. Many models of replication fork reactivation invoke nascent strand regression as an intermediate in the processing of the stalled fork. We have investigated the replication fork regression activity of RecG and RuvAB, two proteins commonly thought to be involved in the process, using a reconstituted DNA replication system where the replisome is stalled by collision with leading-strand template damage. We find that both RecG and RuvAB can regress the stalled fork in the presence of the replisome and SSB; however, RuvAB generates a completely unwound product consisting of the paired nascent leading and lagging strands, whereas RuvC cleaves the Holliday junction generated by RecG-catalyzed fork regression. We also find that RecG stimulates RuvAB-catalyzed regression, presumably because it is more efficient at generating the initial Holliday junction from the stalled fork. PMID- 25138217 TI - Regression of replication forks stalled by leading-strand template damage: II. Regression by RecA is inhibited by SSB. AB - Stalled replication forks are sites of chromosome breakage and the formation of toxic recombination intermediates that undermine genomic stability. Thus, replication fork repair and reactivation are essential processes. Among the many models of replication fork reactivation is one that invokes fork regression catalyzed by the strand exchange protein RecA as an intermediate in the processing of the stalled fork. We have investigated the replication fork regression activity of RecA using a reconstituted DNA replication system where the replisome is stalled by collision with leading-strand template damage. We find that RecA is unable to regress the stalled fork in the presence of the replisome and SSB. If the replication proteins are removed from the stalled fork, RecA will catalyze net regression as long as the Okazaki fragments are sealed. RecA-generated Holliday junctions can be detected by RuvC cleavage, although this is not a robust reaction. On the other hand, extensive branch migration by RecA, where a completely unwound product consisting of the paired nascent leading and lagging strands is produced, is observed under conditions where RuvC activity is suppressed. This branch migration reaction is inhibited by SSB, possibly accounting for the failure of RecA to generate products in the presence of the replication proteins. Interestingly, we find that the RecA-RuvC reaction is supported to differing extents, depending on the template damage; templates carrying a cyclopyrimidine dimer elicit more RecA-RuvC product than those carrying a synthetic abasic site. This difference could be ascribed to a higher affinity of RecA binding to DNAs carrying a thymidine dimer than to those with an abasic site. PMID- 25138218 TI - Formation of amyloid fibers by monomeric light chain variable domains. AB - Systemic light chain amyloidosis is a lethal disease characterized by excess immunoglobulin light chains and light chain fragments composed of variable domains, which aggregate into amyloid fibers. These fibers accumulate and damage organs. Some light chains induce formation of amyloid fibers, whereas others do not, making it unclear what distinguishes amyloid formers from non-formers. One mechanism by which sequence variation may reduce propensity to form amyloid fibers is by shifting the equilibrium toward an amyloid-resistant quaternary structure. Here we identify the monomeric form of the Mcg immunoglobulin light chain variable domain as the quaternary unit required for amyloid fiber assembly. Dimers of Mcg variable domains remain stable and soluble, yet become prone to assemble into amyloid fibers upon disassociation into monomers. PMID- 25138219 TI - Nod-like receptor protein 3 (NLRP3) inflammasome activation and podocyte injury via thioredoxin-interacting protein (TXNIP) during hyperhomocysteinemia. AB - NADPH oxidase-derived reactive oxygen species (ROS) have been reported to activate NLRP3 inflammasomes resulting in podocyte and glomerular injury during hyperhomocysteinemia (hHcys). However, the mechanism by which the inflammasome senses ROS is still unknown in podocytes upon hHcys stimulation. The current study explored whether thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of the antioxidant thioredoxin and ROS sensor, mediates hHcys-induced NLRP3 inflammasome activation and consequent glomerular injury. In cultured podocytes, size exclusion chromatography and confocal microscopy showed that inhibition of TXNIP by siRNA or verapamil prevented Hcys-induced TXNIP protein recruitment to form NLRP3 inflammasomes and abolished Hcys-induced increases in caspase-1 activity and IL-1beta production. TXNIP inhibition protected podocytes from injury as shown by normal expression levels of podocyte markers, podocin and desmin. In vivo, adult C57BL/6J male mice were fed a folate-free diet for 4 weeks to induce hHcys, and TXNIP was inhibited by verapamil (1 mg/ml in drinking water) or by local microbubble-ultrasound TXNIP shRNA transfection. Evidenced by immunofluorescence and co-immunoprecipitation studies, glomerular inflammasome formation and TXNIP binding to NLRP3 were markedly increased in mice with hHcys but not in TXNIP shRNA-transfected mice or those receiving verapamil. Furthermore, TXNIP inhibition significantly reduced caspase-1 activity and IL 1beta production in glomeruli of mice with hHcys. Correspondingly, TXNIP shRNA transfection and verapamil attenuated hHcys-induced proteinuria, albuminuria, glomerular damage, and podocyte injury. In conclusion, our results demonstrate that TXNIP binding to NLRP3 is a key signaling mechanism necessary for hHcys induced NLRP3 inflammasome formation and activation and subsequent glomerular injury. PMID- 25138222 TI - Sustained remission of blastic plasmacytoid dendritic cell neoplasm after unrelated allogeneic stem cell transplantation--a single center experience. AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematodermic neoplasm which typically presents with skin infiltrates with or without lymphadenopathy and bone marrow involvement. No standard of care exists for this aggressive disease and prognosis is particularly poor. Here, we present our experience with nine BPDCN patients diagnosed at our institution between 2005 and 2012. BPDCN patients were identified in the databases at the Department of Hematology and Oncology, the Department of Dermatology, and the Institute of Pathology at the Otto-von-Guericke-University Magdeburg. There were six male and three female patients with a median age at diagnosis of 66 years. Sites involved were skin (five cases), lymph nodes (five cases), and bone marrow (five cases). Treatments varied from single agent chemotherapy to polychemotherapy and allogeneic stem cell transplantation for consolidation. The three patients that were treated with acute leukemia-type induction therapy followed by allogeneic stem cell transplantation (one after standard conditioning and two after reduced intensity conditioning using fludarabine in combination with thiotepa) achieved sustained remissions and are alive with a follow-up of 8, 35, and 41 months. In contrast, median survival in the less intensively treated patients was only 9.5 (range 1 to 29) months. PMID- 25138221 TI - Roles of Bacillus subtilis DprA and SsbA in RecA-mediated genetic recombination. AB - Bacillus subtilis competence-induced RecA, SsbA, SsbB, and DprA are required to internalize and to recombine single-stranded (ss) DNA with homologous resident duplex. RecA, in the ATP . Mg(2+)-bound form (RecA . ATP), can nucleate and form filament onto ssDNA but is inactive to catalyze DNA recombination. We report that SsbA or SsbB bound to ssDNA blocks the RecA filament formation and fails to activate recombination. DprA facilitates RecA filamentation; however, the filaments cannot engage in DNA recombination. When ssDNA was preincubated with SsbA, but not SsbB, DprA was able to activate DNA strand exchange dependent on RecA . ATP. This work demonstrates that RecA . ATP, in concert with SsbA and DprA, catalyzes DNA strand exchange, and SsbB is an accessory factor in the reaction. In contrast, RecA . dATP efficiently catalyzes strand exchange even in the absence of single-stranded binding proteins or DprA, and addition of the accessory factors marginally improved it. We proposed that the RecA-bound nucleotide (ATP and to a lesser extent dATP) might dictate the requirement for accessory factors. PMID- 25138220 TI - Rapid binding of plasminogen to streptokinase in a catalytic complex reveals a three-step mechanism. AB - Rapid kinetics demonstrate a three-step pathway of streptokinase (SK) binding to plasminogen (Pg), the zymogen of plasmin (Pm). Formation of a fluorescently silent encounter complex is followed by two conformational tightening steps reported by fluorescence quenches. Forward reactions were defined by time courses of biphasic quenching during complex formation between SK or its COOH-terminal Lys(414) deletion mutant (SKDeltaK414) and active site-labeled [Lys]Pg ([5 (acetamido)fluorescein]-D-Phe-Phe-Arg-[Lys]Pg ([5F]FFR-[Lys]Pg)) and by the SK dependences of the quench rates. Active site-blocked Pm rapidly displaced [5F]FFR [Lys]Pg from the complex. The encounter and final SK .[5F]FFR-[Lys]Pg complexes were weakened similarly by SK Lys(414) deletion and blocking of lysine-binding sites (LBSs) on Pg kringles with 6-aminohexanoic acid or benzamidine. Forward and reverse rates for both tightening steps were unaffected by 6-aminohexanoic acid, whereas benzamidine released constraints on the first conformational tightening. This indicated that binding of SK Lys(414) to Pg kringle 4 plays a role in recognition of Pg by SK. The substantially lower affinity of the final SK . Pg complex compared with SK . Pm is characterized by a ~ 25-fold weaker encounter complex and ~ 40-fold faster off-rates for the second conformational step. The results suggest that effective Pg encounter requires SK Lys(414) engagement and significant non-LBS interactions with the protease domain, whereas Pm binding additionally requires contributions of other lysines. This difference may be responsible for the lower affinity of the SK . Pg complex and the expression of a weaker "pro"-exosite for binding of a second Pg in the substrate mode compared with SK . Pm. PMID- 25138223 TI - Good lateral harmonic stability combined with adequate gait speed is required for low fall risk in older people. AB - BACKGROUND: Good lateral harmonic stability in gait may be important for minimising fall risk in older people because many falls occur during walking when the base of support is narrowest in the mediolateral (ML) direction. However, the traditional ML harmonic ratio (MLHR) may be a sub-optimal measure of gait quality because of insufficient frequency resolution. OBJECTIVE: The primary objective was to investigate if a new measure of lateral harmonic stability, the 8-step MLHR, could discriminate older fallers from non-fallers while taking different walking speeds into account. METHODS: Repeat walks over 20 m were completed by 96 older people (mean age 80, SD 4 years); 35 participants had a history of one or more falls in the past year. The traditional MLHR and the 8-step MLHR were obtained from an accelerometer attached to the sacrum. RESULTS: Compared to the traditional MLHR, the 8-step MLHR demonstrated similar univariate ability to identify significant differences in fall risk based on age, walking speed and physiology (p <= 0.05). When differences in walking speed were taken into account, we observed that participants who walked both faster than average and had above-average lateral harmonic stability (by the 8-step MLHR) were 5.3 times less likely to be fallers than all other participants (relative risk: 0.19, 95% confidence interval: 0.06-0.57). For the traditional MLHR, however, no significant differences between the fallers and non-fallers were evident. CONCLUSIONS: The findings indicate that good lateral harmonic stability interacts with adequate gait speed and, when coincident, are associated with reduced fall risk in older people. Future research could examine whether interventions focusing on enhancing both gait speed and lateral stability can reduce fall risk and whether these combined gait measures can remotely predict deteriorating health using wearable technology. PMID- 25138224 TI - Efficacy and tolerability of fixed-combination brinzolamide/timolol in Latin American patients with open-angle glaucoma or ocular hypertension previously on brimonidine/timolol fixed combination. AB - INTRODUCTION: Fixed-combination glaucoma medications are commonly used to achieve target intraocular pressure (IOP) reduction in patients uncontrolled with monotherapy; however, ocular discomfort associated with eye drops can decrease adherence. This study assessed the efficacy and tolerability of twice-daily fixed combination brinzolamide 1%/timolol 0.5% (BRINZ/TIM-FC) in Latin American patients transitioned from fixed-combination brimonidine 0.2%/timolol 0.5% (BRIM/TIM-FC) because of insufficient IOP control or treatment intolerance. METHODS: This 8-week, open-label, prospective study was conducted at six sites in Argentina, Chile, and Mexico. Enrolled patients were aged >=18 years with open angle glaucoma (including primary, exfoliative, or pigment-dispersion glaucoma) or ocular hypertension with IOP of 19-35 mmHg in >=1 eye at baseline (on BRIM/TIM FC). Patients self-administered BRINZ/TIM-FC to both eyes at 8 a.m. and 8 p.m. daily for 8 weeks. The primary and secondary efficacy endpoints were mean IOP change from baseline at week 8 and percentage of patients achieving target IOP (<=18 mmHg) at week 8, respectively. Exploratory endpoints included patient and investigator preference for treatment at week 8. Adverse events (AEs) were assessed as the safety endpoint. RESULTS: Fifty patients (mean +/- SD age, 66.7 +/- 11.5 years) received BRINZ/TIM-FC, and 49 were included in the intent-to treat population. Mean +/- SD IOP was significantly reduced from baseline after 8 weeks of treatment with BRINZ/TIM-FC (-3.6 +/- 3.0 mmHg; P < 0.0001, Wilcoxon signed-rank test; 17.1% reduction). Overall, 55.3% of patients achieved IOP <=18 mmHg at week 8. Significantly more patients (89.4%) and investigators (95.7%) preferred BRINZ/TIM-FC to BRIM/TIM-FC (both P < 0.0001, exact binomial test). Of the 13 AEs observed, 8 were related to BRINZ/TIM-FC; the most common treatment related AEs were eye irritation (n = 4) and abnormal sensation in the eye (n = 2). CONCLUSION: BRINZ/TIM-FC provides an effective and well-tolerated treatment option for patients transitioned from BRIM/TIM-FC. PMID- 25138225 TI - Syphilis Infection: An Uncommon Etiology of Infectious Nonimmune Fetal Hydrops with Anemia. AB - An increased prevalence of syphilis has been observed in many developed countries over the last decade. During pregnancy, syphilis can affect the fetus through development of nonspecific symptoms such as microcephaly, ascites, hepatosplenomegaly, dilated and echogenic bowel, placentomegaly, and, uncommonly, fetal hydrops. Congenital syphilis also leads to hematologic abnormalities such as anemia, thrombocytopenia, leukopenia, and leukocytosis. We present a case of nonimmune fetal hydrops with anemia related to syphilis infection. Diagnosis was confirmed by a maternal serological test and microbiological testing on amniotic fluid, umbilical cord, and placental tissues. The patient was treated with penicillin and the fetus received an intrauterine red blood cell transfusion, but fetal death occurred shortly after. Such a presentation is mostly related to parvovirus B19, and syphilis etiology is poorly mentioned because physicians have rarely seen early congenital syphilis in the past. However, given the increasing prevalence of this disease in the adult population, clinicians should remain alert to the various presentations of congenital syphilis. PMID- 25138227 TI - Secretoneurin as a marker for hypoxic brain injury after cardiopulmonary resuscitation. AB - PURPOSE: The neuropeptide secretoneurin (SN) shows widespread distribution in the brain. We evaluated whether SN is elevated after cardiopulmonary resuscitation (CPR) and could serve as a potential new biomarker for hypoxic brain injury after CPR. METHODS: This was a prospective observational clinical study. All patients admitted to a tertiary medical intensive care unit after successful CPR with expected survival of at least 24 h were consecutively enrolled from September 2008 to April 2013. Serum SN and neuron-specific enolase were determined in 24 h intervals starting with the day of CPR for 7 days. Neurological outcome was assessed with the Cerebral Performance Categories Scale (CPC) at hospital discharge. RESULTS: A total of 134 patients were included with 49 % surviving to good neurological outcome (CPC 1-2). SN serum levels peaked within the first 24 h showing on average a sixfold increase above normal. SN levels were significantly higher in patients with poor (CPC 3-5) than in patients with good neurological outcome [0-24 h: 75 (43-111) vs. 38 (23-68) fmol/ml, p < 0.001; 24-48 h: 45 (24 77) vs. 23 (16-39) fmol/ml, p < 0.001]. SN determined within the first 48 h showed a receiver operating characteristic (ROC) area under the curve (AUC) of 0.753 (0.665-0.841). NSE in the first 72 h had a ROC-AUC of 0.881 (0.815-0.946). When combining the two biomarkers an AUC of 0.925 (0.878-0.972) for outcome prediction could be reached. CONCLUSIONS: SN is a promising early biomarker for hypoxic brain injury. Further studies will be required for confirmation of these results. PMID- 25138228 TI - Understanding incretins. PMID- 25138230 TI - Ask the wrong question, you'll the get the wrong answer. PMID- 25138229 TI - PROF-ETEV study: prophylaxis of venous thromboembolic disease in critical care units in Spain. AB - PURPOSE: Venous thromboembolic disease (VTE) in critically ill patients has a high incidence despite prophylactic measures. This fact could be related to an inappropriate use of these measures due to the absence of specific VTE risk scores. To assess the current situation in Spain, we have performed a cross sectional study, analyzing if the prophylactic measures were appropriate to the patients' VTE risk. METHODS: Through an electronic questionnaire, we carried out a single day point prevalence study on the VTE prophylactic measures used in several critical care units in Spain. We performed a risk stratification for VTE in three groups: low, moderate-high, and very high risk. The American College of Chest Physicians guidelines were used to determine if the patients were receiving the recommended prophylaxis. RESULTS: A total of 777 patients were included; 62% medical, 30% surgical, and 7% major trauma patients. The median number of the risk factors for VTE was four. According to the proposed VTE risk score, only 2% of the patients were at low risk, whereas 83% were at very high risk. Sixty-three percent of patients received pharmacological prophylaxis, 12% mechanical prophylaxis, 6% combined prophylaxis, and 19% did not receive any prophylactic measure. According to criteria suggested by the guidelines, 23% of medical, 71% of surgical, and 70% of major trauma patients received an inappropriate prophylaxis. CONCLUSIONS: Most critically ill patients are at high or very high risk of VTE, but there is a low rate of appropriate prophylaxis. The efforts to improve the identification of patients at risk, and the implementation of appropriate prevention protocols should be enhanced. PMID- 25138226 TI - Consensus summary statement of the International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care : a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine. AB - Neurocritical care depends, in part, on careful patient monitoring but as yet there are little data on what processes are the most important to monitor, how these should be monitored, and whether monitoring these processes is cost effective and impacts outcome. At the same time, bioinformatics is a rapidly emerging field in critical care but as yet there is little agreement or standardization on what information is important and how it should be displayed and analyzed. The Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine, and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to begin to address these needs. International experts from neurosurgery, neurocritical care, neurology, critical care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on the basis of their research, publication record, and expertise. They undertook a systematic literature review to develop recommendations about specific topics on physiologic processes important to the care of patients with disorders that require neurocritical care. This review does not make recommendations about treatment, imaging, and intraoperative monitoring. A multidisciplinary jury, selected for their expertise in clinical investigation and development of practice guidelines, guided this process. The GRADE system was used to develop recommendations based on literature review, discussion, integrating the literature with the participants' collective experience, and critical review by an impartial jury. Emphasis was placed on the principle that recommendations should be based on both data quality and on trade-offs and translation into clinical practice. Strong consideration was given to providing pragmatic guidance and recommendations for bedside neuromonitoring, even in the absence of high quality data. PMID- 25138231 TI - Ten years' experience for hypospadias repair: combined buccal mucosa graft and local flap for urethral reconstruction. AB - OBJECTIVES: To share our experience in hypospadias repair and discuss the clinical implications of our method, which consists of a combined buccal mucosa graft and local flap for urethroplasty. PATIENTS AND METHODS: 1,394 cases (median age 11.3 years, age range 5 months to 53 years) of hypospadias which were repaired using our method between July 2000 and December 2010 in our department were included in this study. The patients who had a short penis or did not have chordee were excluded from the data. 588 cases (42.2%) had previously undergone surgery in other hospitals but failed; 806 (57.8%) cases had undergone the first treatment in our department. RESULTS: Of the 806 cases which had undergone the first treatment in our department, we successfully reconstructed the urethra for 747 patients (92.3%), and 59 patients had complications (7.7%); of the 588 cases which had previously undergone surgery but failed, we successfully reconstructed the urethra for 522 patients (88.8%), and 66 patients had complications (11.2%). The most common complication was urethra fistula (70; 5%); other complications include necrosis of the skin flap and infection resulting in wound disruption (19; 1.4%), urethral diverticula (11; 0.8%) and urethral stricture (25; 1.8%). CONCLUSIONS: Our method appears to be a safe, simple and satisfactory surgical procedure and can provide relatively enough tissue to reconstruct the urethra with a higher success rate. PMID- 25138232 TI - Caudal lumbar vertebral fractures in California Quarter Horse and Thoroughbred racehorses. AB - REASONS FOR PERFORMING STUDY: To gain insight into the pathophysiology of equine lumbar vertebral fractures in racehorses. OBJECTIVES: To characterise equine lumbar vertebral fractures in California racehorses. STUDY DESIGN: Retrospective case series and prospective case-control study. METHODS: Racehorse post mortem reports and jockey injury reports were retrospectively reviewed. Vertebral specimens from 6 racehorses affected with lumbar vertebral fractures and 4 control racehorses subjected to euthanasia for nonspinal fracture were assessed using visual, radiographic, computed tomography and histological examinations. RESULTS: Lumbar vertebral fractures occurred in 38 Quarter Horse and 29 Thoroughbred racehorses over a 22 year period, primarily involving the 5th and/or 6th lumbar vertebrae (L5-L6; 87% of Quarter Horses and 48% of Thoroughbreds). Lumbar vertebral fractures were the third most common musculoskeletal cause of death in Quarter Horses and frequently involved a jockey injury. Lumbar vertebral specimens contained anatomical variations in the number of vertebrae, dorsal spinous processes and intertransverse articulations. Lumbar vertebral fractures examined in 6 racehorse specimens (5 Quarter Horses and one Thoroughbred) coursed obliquely in a cranioventral to caudodorsal direction across the adjacent L5-L6 vertebral endplates and intervertebral disc, although one case involved only one endplate. All cases had evidence of abnormalities on the ventral aspect of the vertebral bodies consistent with pre-existing, maladaptive pathology. CONCLUSIONS: Lumbar vertebral fractures occur in racehorses with pre-existing pathology at the L5-L6 vertebral junction that is likely predisposes horses to catastrophic fracture. Knowledge of these findings should encourage assessment of the lumbar vertebrae, therefore increasing detection of mild vertebral injuries and preventing catastrophic racehorse and associated jockey injuries. PMID- 25138233 TI - Unwanted childbearing and household food insecurity in the United States. AB - Household food insecurity is a population health concern disproportionately affecting families with children in the United States. Unwanted childbearing may place unanticipated strain on families to meet basic needs, heightening the risk for household food insecurity. We investigated the association between mother's and father's report of unwanted childbearing and exposure to household food insecurity among children residing in two-parent households in the United States. Data from the Early Childhood Longitudinal Study - Birth Cohort, a nationally representative cohort of US children (n ~ 6150), were used to estimate the odds of household food insecurity when children were aged 9 months and 2 years, separately, based on parental report of unwanted childbearing. The majority of children were reported as wanted by both parents (74.4%). Of the sample, report of unwanted childbearing by father-only was 20.0%, mother-only was 3.4% and joint mother and father was 2.2%. Household food insecurity was higher when children were 9 months compared with 2 years. In adjusted models accounting for confounders, children born to mothers and fathers who jointly reported unwanted childbearing were at higher odds of exposure to household food insecurity at 9 months [adjusted odds ratio (AOR) = 3.31; 95% confidence interval (CI): 1.97, 5.57] and 2 years (AOR = 2.52; 95% CI: 1.12, 5.68). In two-parent households, we found that children raised by parents reporting unwanted childbearing were more likely to be exposed to food insecurity and potentially related stressors. Further studies that prospectively measure wantedness before the child's birth will aid in confirming the direction of this association. PMID- 25138235 TI - Current research and recent breakthroughs on the mental health effects of disasters. AB - A large existing academic disaster mental health literature provides a foundation to help guide disaster mental health response. Recent studies, however, have indicated that reconceptualization of certain mental health aspects of disasters may be indicated to guide further research to inform the planning and implementation of disaster mental health interventions. In particular, there is need to more carefully measure specific postdisaster disorders and syndromes using full diagnostic assessments, differentiate pre-existing from incident (new) postdisaster psychopathology, appropriately consider disaster trauma exposure groups in assessing psychopathology, and conduct prospective follow-up assessments over time from the acute postdisaster period to the long term. Further descriptive and longitudinal research is needed to better characterize the occurrence and course of fully-assessed psychiatric disorders after different disasters, clarify the role of disaster trauma exposures in the development of postdisaster psychopathology, and deconstruct confounding effects in determination of causalities in mental health consequences of disasters. PMID- 25138234 TI - Antipsychotic induced weight gain: genetics, epigenetics, and biomarkers reviewed. AB - Antipsychotic-induced weight gain (AIWG) is a prevalent side effect of antipsychotic treatment, particularly with second generation antipsychotics, such as clozapine and olanzapine. At this point, there is virtually nothing that can be done to predict who will be affected by AIWG. However, hope for the future of prediction lies with genetic risk factors. Many genes have been studied for their association with AIWG with a variety of promising findings. This review will focus on genetic findings in the last year and will discuss the first epigenetic and biomarker findings as well. Although there are significant findings in many other genes, the most consistently replicated findings are in the melanocortin 4 receptor (MC4R), the serotonin 2C receptor (HTR2C), the leptin, the neuropeptide Y (NPY) and the cannabinoid receptor 1 (CNR1) genes. The study of genetic risk variants poses great promise in creating predictive tools for side effects such as AIWG. PMID- 25138237 TI - Variation in seminal plasma alters the ability of ram spermatozoa to survive cryopreservation. AB - Variation in the effect of seminal plasma on sperm function and fertility has been hypothesised to be due to differences between males and their seminal plasma composition. The freezing resilience of individual rams (n=17) was investigated to characterise inter-male variation. This was determined by measuring the degree of change in motility induced by cryopreservation (Experiment 1). Experiment 2 examined the effect of pooled seminal plasma from rams identified as having high or low resilience to freezing on the cryosurvival of washed spermatozoa from either high (n=3) or low (n=3) sperm freezing resilience rams. Immediately after thawing and throughout the incubation period (0-4h), spermatozoa from high resilience rams frozen with high-resilience seminal plasma demonstrated superior motility to spermatozoa from high-resilience rams frozen with low-resilience seminal plasma (P<0.001). Similarly, spermatozoa from low-resilience rams frozen with high-resilience seminal plasma exhibited higher motility than spermatozoa from low-resilience rams frozen with low-resilience seminal plasma immediately after thawing (0h; P<0.001). The present study shows that variation in freezing resilience of ram spermatozoa is related to the source and composition of the seminal plasma. PMID- 25138236 TI - Pharmacotherapy of anxiety disorders in German-speaking countries: current status and changes between 1994 and 2011. AB - Over the past years, international treatment guidelines have been established for the treatment of anxiety disorders. Nevertheless, little is known as to whether the actual inpatient treatment follows these guidelines. The main goal of this study was to answer the question whether patients with anxiety disorder are treated according to treatment guidelines. A total of 2,573 psychiatric inpatients with the diagnosis of anxiety disorder (920 men, 1,653 women) were identified on the basis of the data of the international drug safety programme in psychiatry AMSP. Of these patients, 25.3% presented with phobia, 26.6% with panic disorder, 18.7% with generalized anxiety disorder (GAD), and 29.4% with other diagnoses of anxiety. In all of the patients, 12.7% did not receive any psychotropic medication and 22.9% were not treated with antidepressants. Only 59.3% of patients with GAD, 73.9% of patients with panic disorder, and 52.1% of patients with phobia were treated according to diagnostic guidelines. The majority (60.3%) of all patients received one or two psychotropic drugs, and only 3.7% received five or more psychotropic drugs. In two groups of patients (one group with phobia and one with panic disorder), the annual prescription rate of antidepressants significantly increased over time. The prescription rate for anticonvulsants in patients with GAD increased from 0% in 1997 to 41.7% in 2011, and for antipsychotics, from 40.7% in 1997 to 47.2% in 2011. In particular, patients with GAD were commonly treated with antipsychotics. PMID- 25138238 TI - PIXSIC, a pixelated beta+-sensitive probe for radiopharmacological investigations in rat brain: binding studies with [18F]MPPF. AB - PURPOSE: The aim of this work was to demonstrate the pharmacokinetic potential of a wireless pixelated beta(+)-sensitive probe (PIXSIC). PROCEDURES: The binding of 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine ([(18)F]MPPF), a 5-HT1A serotonin receptor radiopharmaceutical, was measured in anesthetized rats and compared to microPET data. The effects of a 5-HT1A antagonist injection on in vivo [(18)F]MPPF binding were monitored by PIXSIC. RESULTS: PIXSIC allowed differentiating the radioactive kinetics according to the location of its pixels in the hippocampus, cortex, corpus callosum, and cerebellum. The device accurately detected the changes in [(18)F]MPPF binding, after 5-HT1A antagonist blockade. The time-activity curves were reproducible and consistent with kinetics obtained simultaneously with a microPET camera. CONCLUSIONS: These results demonstrate the ability of the PIXSIC device to record reliably the binding of PET ligands, with a high spatiotemporal resolution in anesthetized rodents. These first in vivo results are a key stage on the path to its implementation in awake freely moving animals. PMID- 25138240 TI - Dislocation mechanism of deuterium retention in tungsten under plasma implantation. AB - We have developed a new theoretical model for deuterium (D) retention in tungsten based alloys on the basis of its being trapped at dislocations and transported to the surface via the dislocation network with parameters determined by ab initio calculations. The model is used to explain experimentally observed trends of D retention under sub-threshold implantation, which does not produce stable lattice defects to act as traps for D in conventional models. Saturation of D retention with implantation dose and effects due to alloying of tungsten with, e.g. tantalum, are evaluated, and comparison of the model predictions with experimental observations under high-flux plasma implantation conditions is presented. PMID- 25138239 TI - Hypomagnesaemia associated with long-term use of proton pump inhibitors. AB - Hypomagnesaemia and associated hypocalcaemia and hypoparathyroidism have been increasingly recognised as rare long-term side-effects of proton pump inhibitors (PPIs). The PPIs may inhibit active magnesium (Mg) absorption by interfering with transcellular transient receptor potential melastatin-6 and -7 (TRPM 6 and 7) channels. More recent cell culture studies have suggested concomitant inhibition of passive Mg absorption by omeprazole. After being treated with a range of PPIs, the four patients in our case series developed hypomagnesaemia, which responded to withdrawal of therapy and initiation of Mg replacement. Their clinical course and management demonstrate key aspects of hypomagnesaemia associated with long term use of PPIs. PMID- 25138241 TI - Analysis of the Italian generic medicines retail market: recommendations to enhance long-term sustainability. AB - Italy is among the European countries with the lowest uptake of generic medicines. This paper provides a perspective on the Italian generic medicines retail market. Fast market entrance of generic medicines in Italy is hindered by several factors: the existence of Complementary Protection Certificates in the past, the large market for copies and multiple cases of patent linkage. Prices of generic medicines in Italy are low compared to other European countries. To contain pharmaceutical expenditure, pharmaceutical companies are currently forced to pay back in case of overspending, which disproportionally penalizes small and fast growing companies, to which most generic companies belong to. Current demand side policies do not successfully stimulate the use of generic medicines. The current market environment surrounding the Italian generic medicines retail market (i.e., low prices, low volumes) threatens its long-term sustainability. Recommendations to enhance the long-term sustainability of the Italian generic medicines retail market round off this perspective paper. PMID- 25138243 TI - Central versus peripheral arterial cannulation and neurological outcomes after thoracic aortic surgery: meta-analysis and meta-regression of 4459 patients. AB - BACKGROUND: Thoracic aortic surgeries remain with high mortality rates, often associated with postoperative neurological complications. The choice of the right cannulation site is extremely important for suitable blood supply and maintenance of vital functions, especially of the central nervous system. OBJECTIVES: To compare the influence of central versus peripheral arterial cannulation on neurological outcomes in patients undergoing thoracic aortic surgery through systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS and reference lists of relevant articles were searched for clinical studies that reported in-hospital neurological outcomes after central or peripheral arterial cannulation during thoracic aortic surgery procedures until December 2013. The principal summary measures were Odds Ratio (OR) for central compared to peripheral arterial cannulation with 95% confidence interval (CI) and p-values considered statistically significant when <0.05. The ORs were combined across studies, using the DerSimonian-Laird random effects model and fixed effects model using the Mantel-Haenszel model--both models were weighted. The meta-analysis was completed using the software Comprehensive Meta-Analysis version 2 (Biostat Inc., Englewood, NJ). RESULTS: Six studies were identified and included a total of 4459 patients (1180 for central and 3279 for peripheral cannulation). There was no significant difference between the central and peripheral groups regarding neurological outcomes. The meta-regression evidenced no relationship between neurological outcomes and the variables age, sex, previous coronary event, previous neurological event, urgency surgery, cardiopulmonary bypass time, activated clotting time and esophageal temperature with p > 0,05. CONCLUSION: When it comes to neurological outcomes in patients undergoing thoracic aortic surgery, there was no evidence that argues in favor of any choice of arterial cannulation site, which makes us reject any superiority of one approach over the other in this regard. PMID- 25138242 TI - The regulatory effect of UL-16 binding protein-3 expression on the cytotoxicity of NK cells in cancer patients. AB - The activating immunoreceptor NKG2D (natural killer group 2, member D) and its ligands play important roles in the innate and adaptive immune responses. UL16 binding protein 3 (ULBP3), an NKG2D ligand, is overexpressed on certain epithelial tumor cells. In this study, we investigated the effect of ULBP3 expression on the cytotoxic activity of natural killer (NK) cells. ULBP3 were measured by flow cytometry analysis, immunohistochemistry, and time-resolved fluoroimmunoassay. The cytotoxicity of NK cells was determined with the lactate dehydrogenase release assay. We found that ULBP3 was overexpressed on tumor cell lines and tumor tissues. Serum from cancer patients, but not from healthy donors, contained elevated levels of soluble ULBP3 (sULBP3). Importantly, high expression of ULBP3 on the cell surface of tumor cells augmented NKG2D-mediated NK cell cytotoxicity. However, low levels of sULBP3 (<15 ng/ml) weakened the cytotoxicity of NK cells by decreasing NKG2D expression on NK cells. Further analysis showed that serum samples from most cancer patients (>70%) contained the low level of sULBP3. Our results demonstrate that tumor cells express surface and soluble ULBP3, which regulate NK cell activity. Thus, ULBP3 is a potential therapeutic target for improving the immune response against cancer. PMID- 25138244 TI - Real-time data acquisition and alerts may reduce reaction time and improve perfusionist performance during cardiopulmonary bypass. AB - Delayed perfusionist identification and reaction to abnormal clinical situations has been reported to contribute to increased mortality and morbidity. The use of automated data acquisition and compliance safety alerts has been widely accepted in many industries and its use may improve operator performance. A study was conducted to evaluate the reaction time of perfusionists with and without the use of compliance alert. A compliance alert is a computer-generated pop-up banner on a pump-mounted computer screen to notify the user of clinical parameters outside of a predetermined range. A proctor monitored and recorded the time from an alert until the perfusionist recognized the parameter was outside the desired range. Group one included 10 cases utilizing compliance alerts. Group 2 included 10 cases with the primary perfusionist blinded to the compliance alerts. In Group 1, 97 compliance alerts were identified and, in group two, 86 alerts were identified. The average reaction time in the group using compliance alerts was 3.6 seconds. The average reaction time in the group not using the alerts was nearly ten times longer than the group using computer-assisted, real-time data feedback. Some believe that real-time computer data acquisition and feedback improves perfusionist performance and may allow clinicians to identify and rectify potentially dangerous situations. PMID- 25138246 TI - Predictive factors for clinical response to allergy immunotherapy in children with asthma and rhinitis. AB - BACKGROUND: To date, no predictive methods for the clinical response to allergy immunotherapy (AIT) are available. We sought to evaluate the pretreatment parameters used in diagnosing allergic asthma and/or rhinitis including allergen skin-prick test responses, serum specific and total IgE (sIgE and tIgE) levels and blood eosinophil counts, and to identify whether these can be used to predict clinical effectiveness in children treated with immunotherapy. METHODS: This study involved 185 children who had undergone 3 years of standardized-quality house-dust mite subcutaneous immunotherapy. Clinical characteristics and laboratory parameters were analyzed. A multivariate unconditional logistic regression model and receiver operating characteristic curves were used. Predicted probabilities and predictive areas under the curve were calculated. RESULTS: The clinical response to AIT was effective in 129/185 (69.7%) patients. Four variables were associated with clinical response by multivariate logistic analysis: tobacco smoke exposure [odds ratio (OR) 2.845 and 95% confidence interval (CI) 1.147-7.058; p = 0.024], a family history of atopy (OR 2.881 and 95% CI 1.240-6.692; p = 0.014), a serum tIgE level >=965 kU/l (OR 5.917 and 95% CI 2.320-15.089; p = 0.000) and an sIgE/tIgE ratio >=6% (OR 0.336 and 95% CI 0.124-0.911; p = 0.032). The sensitivity and specificity of the area under the curve of the serum tIgE were higher than those of serum sIgE and sIgE/tIgE ratio alone. CONCLUSION: Tobacco smoke exposure, atopic family history, serum tIgE and sIgE/tIgE ratio were in significant correlation with clinical response to AIT in children, which may be helpful for patient selection before immunotherapy. The serum tIgE is superior to both the serum sIgE/tIgE ratio and sIgE levels alone in predicting clinical effectiveness. PMID- 25138248 TI - Negative Religious Coping Predicts Disordered Eating Pathology Among Orthodox Jewish Adolescent Girls. AB - Recent research suggests the importance of exploring religious and spiritual factors in relation to the continuum of disordered eating. This continuum ranges from mild disordered eating behaviors and attitudes to moderate levels of disordered eating pathology (DEP) through full-blown clinical levels of eating disorders (EDs). The current study is the first to explore the role that religious coping (both positive and negative) plays in the development DEP, which is considered a risk factor for the development of EDs. In addition, the study aims to describe levels of DEP among a non-clinical sample of 102 Orthodox Jewish adolescent females. Participants completed a questionnaire measuring religious coping strategies, DEP and self-esteem. Results indicated that greater use of negative religious coping was associated with higher levels of DEP. Mediation analyses suggested that greater negative religious coping is related to lower levels of self-esteem, which accounts for higher levels of DEP. Furthermore, findings revealed relatively lower overall levels of DEP among this sample, compared to similar populations in Israel and the USA. These results suggest that a strong religious and spiritual identity may serve as a protective factor against DEP. PMID- 25138249 TI - Impaired left atrial function in heart failure with preserved ejection fraction. AB - AIMS: Left atrial (LA) enlargement is present in the majority of heart failure with preserved ejection fraction (HFpEF) patients and is a marker of risk. However, the importance of LA function in HFpEF is less well understood. METHODS AND RESULTS: The PARAMOUNT trial enrolled HFpEF patients (LVEF >=45%, NT-proBNP >400 pg/mL). We assessed LA reservoir, conduit, and pump function using two dimensional volume indices and speckle tracking echocardiography in 135 HFpEF patients in sinus rhythm at the time of echocardiography and 40 healthy controls of similar age and gender. Systolic LA strain was related to clinical characteristics and measures of cardiac structure and function. Compared with controls, HFpEF patients had worse LA reservoir, conduit, and pump function. The differences in systolic LA strain (controls 39.2 +/- 6.6% vs. HFpEF 24.6 +/- 7.3%) between groups remained significant after adjustments and even in the subsets of HFpEF patients with normal LA size or without a history of AF. Among HFpEF patients, lower systolic LA strain was associated with higher prevalence of prior HF hospitalization and history of AF, as well as worse LV systolic function, and higher LV mass and LA volume. However, NT-proBNP and E/E' were similar across the quartiles of LA function. CONCLUSIONS: In this HFpEF cohort, we observed impairment in all phases of LA function, and systolic LA strain was decreased independent of LA size or history of AF. LA dysfunction may be a marker of severity and play a pathophysiological role in HFpEF. TRIAL REGISTRATION: NCT00887588. PMID- 25138251 TI - Angiopep-2 and activatable cell penetrating peptide dual modified nanoparticles for enhanced tumor targeting and penetrating. AB - Delivering chemotherapeutics by nanoparticles into tumor was influenced by at least two factors: specific targeting and highly efficient penetrating of the nanoparticles. In this study, two targeting ligands, angiopep-2 and activatable cell penetrating peptide (ACP), were functionalized onto nanoparticles for tumor targeting delivery. In this system, angiopep-2 is a ligand of low-density lipoprotein receptor-related protein-1 (LRP1) which was highly expressed on tumor cells, and the ACP was constructed by the conjugation of RRRRRRRR (R8) with EEEEEEEE through a matrix metalloproteinase-2 (MMP-2) sensitive linker, enabling the ACP with tumor microenvironment-responsive cell penetrating property. 4h incubation of ACP with MMP-2 leads to over 80% cleavage of ACP, demonstrating ACP indeed possessed MMP-2 responsive property. The constructed dual targeting nanoparticles (AnACNPs) were approximately 110 nm with a polydispersity index of 0.231. In vitro, ACP modification and angiopep-2 modification could both enhance the U-87 MG cell uptake because of the high expression of MMP-2 and LRP-1 on C6 cells. AnACNPs showed higher uptake level than the single ligand modified nanoparticles. The uptake of all particles was time- and concentration-dependent and endosomes were involved. In vivo, AnACNPs showed best tumor targeting efficiency. The distribution of AnACNPs in tumor was higher than all the other particles. After microvessel staining with anti-CD31 antibody, the fluorescent distribution demonstrated AnACNPs could distribute in the whole tumor with the highest intensity. In conclusion, a novel drug delivery system was developed for enhanced tumor dual targeting and elevated cell internalization. PMID- 25138250 TI - Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ hydrogel based on poloxamer 407 and carrageenan. AB - The objective of this study was to construct a new in situ gel system based on the combination of poloxamer 407 and carrageenan (carrageenan-poloxamer 407 hydrogel, CPH) for intranasal delivery of ketorolac tromethamine. CPH showed potassium ion concentration - dependent erosion characteristics which ensured slow erosion in aqueous environment containing potassium ion at the physiological level. Loading with ketorolac tromethamine influenced erosion, drug release and thermosensitive properties of CPH. CPH containing 15% ketorolac tromethamine showed suitable gelation temperature (near 35 degrees C) and in vitro sustained release profiles. Pharmacokinetic study of intranasal CPH containing 15% ketorolac tromethamine in rats demonstrated enhanced absolute bioavailability (68.8 +/- 23.3%) and prolonged mean residence time (8.8 +/- 3.5h) in comparison with the intranasal solution group (24.8 +/- 13.8%, 3.9 +/- 0.6h). Nasal ciliotoxicity evaluation on an in situ toad palate model preliminarily showed the safety of CPH for intranasal use. All results suggested the potential of CPH as a new sustained - release platform for the intranasal delivery of ketorolac tromethamine. PMID- 25138252 TI - Liposome-based co-delivery of siRNA and docetaxel for the synergistic treatment of lung cancer. AB - Combination of more than one therapeutic strategy is the standard treatment in clinics. Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) within a nanoparticulate system will suppress the tumor growth. In the present study, docetaxel (DTX) and BCL-2 siRNA was incorporated in a PEGylated liposome to systemically deliver in a lung cancer model (A549). The resulting nanoparticle (lipo-DTX/siRNA) was stable and exhibited a sustained release profile. The co delivery of therapeutic moieties inhibited the cell proliferation (A549 and H226) in a time-dependent manner. Moreover, the co-delivery system of DTX and siRNA exhibited a remarkable apoptosis of cancer cells with elevated levels of caspase 3/7 activity (apoptosis markers). Cell cycle analysis further showed remarkable increase in sub-G0/G1 phase, indicating increasing hypodiploids or apoptotic cells. Pharmacokinetic study showed a long circulating profile for DTX from lipo DTX/siRNA system facilitating the passive tumor targeting. In vivo antitumor study on A549 cell bearing xenograft tumor model exhibited a remarkable tumor regression profile for lipo-DTX/siRNA with 100% survival rate. The favorable tumor inhibition response was attributed to the synergistic effect of DTX potency and MDR reversing ability of BCL-2 siRNA in the tumor mass. Overall, experimental results suggest that co-delivery of DTX and siRNA could be promising approach in the treatment of lung cancers. PMID- 25138254 TI - Development of nanocrystal formulation of meloxicam with improved dissolution and pharmacokinetic behaviors. AB - The present study aimed to develop nanocrystal formulations of meloxicam (MEL) in order to enhance its biopharmaceutical properties and provide a rapid onset of action. Nanocrystal formulations were prepared by wet-milling and lyophilization with hydrophilic polymers used as aggregation inhibitors. Aggregation inhibitors were selected based on high-throughput screening of crystal growth inhibition in supersaturated MEL solution. Supersaturation of MEL was observed in PVP K-30, HPC SSL, and POVACOAT Type F solution. Although the particle size distributions of pulverized MEL with PVP K-30 (MEL/PVP), HPC-SSL (MEL/HPC), and POVACOAT Type F (MEL/POVA) were in the nanometer range following lyophilization, increases in micron-sized aggregates were observed after storage at 60 degrees C for 21 days. The order of increased amount of aggregates was MEL/POVA?MEL/HPC>MEL/PVP. These findings showed that hydrophilic polymers that inhibited crystal growth in supersaturated MEL solutions tended to prevent aggregation. The dissolution behavior of all nanocrystal formulations tested was markedly enhanced compared with that of unpulverized MEL. Oral administration of MEL/PVP showed a 2.0h shortened Tmax and a 5.0-fold increase in bioavailability compared with unpulverized MEL. These findings showed that the MEL/PVP mixture was physicochemically stable and provided a rapid onset of action and enhanced bioavailability after oral administration. PMID- 25138253 TI - Hydroxypropyl-beta-cyclodextrin grafted polyethyleneimine used as transdermal penetration enhancer of diclofenac sodium. AB - The objective of this investigation was to develop a novel cationic polymer, hydroxypropyl-beta-cyclodextrin grafted polyethyleneimine (HP-beta-CD-PEI1800), as a penetration enhancer, and evaluate its viability on improving transdermal delivery of diclofenac sodium. In this study, HP-beta-CD-PEI1800 was characterized by (1)H NMR and DSC methods, respectively. The hydrophilic drug diclofenac sodium was chosen as model drug, and the transdermal permeation enhancement of HP-beta-CD-PEI1800 was estimated in vitro by using Franz diffusion cells fitted with mouse dorsal skins, the in vivo kinetics of diclofenac sodium was analyzed by high-performance liquid chromatography (HPLC). The cumulative drug content deposited in epidermis and dermis was measured at the pre-determined time point of 3, 6, and 9h, and the permeation profile was significantly higher than that of the control groups. In addition, the cytotoxicity and skin irritation of enhancer was evaluated by MTT assay and histological examination, respectively, and the results indicated that the polymer we prepared were non toxic and non-irritant after exposure to skins. All the results suggested that HP beta-CD-PEI1800 could be a safe and efficient penetration enhancer of diclofenac sodium. PMID- 25138255 TI - Formulation and in vitro and in vivo evaluation of a cationic emulsion as a vehicle for improving adenoviral gene transfer. AB - Advancements in the use of adenoviral vectors in gene therapy have been limited by the need for specific receptors on targeted cell types, immunogenicity and hepatotoxicity following systemic administration. In an effort to overcome the current limitations of adenovirus-mediated gene transfer, cationic emulsions were explored as a vehicle to improve adenoviral vector-mediated gene transfer. Complexation of adenovirus with emulsions containing the cationic lipid 1,2 dioleoyl-3-trimethylammonium propane (DOTAP) enhanced the potency of adenoviral gene transfer as compared to DOTAP liposomes. Among the various emulsion formulations examined, those containing the iodized oil, Lipiodol, as an inner core and stabilized by DOTAP/cholesterol/1,2-distearoyl-sn-glycero-3 phosphoethanolamine-N-methoxy(poly-ethylene glycol)-5000 most efficiently enhanced adenovirus-mediated gene transfer. Optimized Lipiodol-containing emulsions appear to be more strongly associated with adenoviral particles, exhibiting higher complex stability compared to other formulations. They provide the adenovirus with an additional cellular entry mechanism through caveolae dependent endocytosis, thereby increasing adenovirus entry into cells. Furthermore, adenovirus-emulsion complexation significantly reduced transgene expression in the liver following systemic administration. These findings indicate that emulsion complexation may be a promising strategy for overcoming many of the challenges associated with the use of adenoviruses in gene therapy. Additionally, the observation of increased transgene expression in lung together with reduced expression in liver demonstrates that the adenovirus-emulsion complex may act as a lung-targeting adenoviral gene delivery system. PMID- 25138256 TI - Amorphous isradipine nanosuspension by the sonoprecipitation method. AB - The aims of this study are to increase and explain the mechanism of dissolution enhancement of isradipine using the sonoprecipitation method for stable nanosuspensions. There have been still few of published researches on formulation of isradipine using nanoparticle engineering. Nanosuspension systems were prepared upon various factors including amplitude and the time length of ultrasonication. The dissolution test was performed according to the USP paddle method in intestinal fluid (pH 6.8). The crystalline structure of drug, the molecular interaction, morphology and size of nanosuspension were also investigated to determine the mechanism of dissolution enhancement. The sonoprecipitation method with use of HPMC 6 showed its potential in enhancement of the drug release rate. Stable nanosuspension was significantly depended on amplitude and time of ultrasonication since these factors affected on the size of nanoparticles. The synergistic effects of reduction of drug crystallinity and particle size could increase the dissolution rate of isradipine by providing a stable nanosuspension. This work may contribute to a new strategy for improvement dissolution rate of isradipine. PMID- 25138257 TI - On the scaling behavior of electric conductivity in [C4mim][NTf2]. AB - In this work we examine, for the first time, the molar conductivity behavior of the deeply supercooled room temperature ionic liquid [C4mim][NTf2] in the temperature, pressure and volume thermodynamic space in terms of density scaling (TV(gamma))(-1) combined with the equation of state (EOS). The exponent gammasigma determined from the Avramov model analysis is compared with the coefficient obtained from the viscosity studies carried out at moderate temperatures. Therefore, the experimental results presented herein provide the answer to the long-standing question regarding the validity of thermodynamic scaling of ionic liquids over a wide temperature range, i.e. from the normal liquid state to the glass transition point. Finally, we investigate the relationship between the dynamic and thermodynamic properties of [C4mim][NTf2] represented by scaling exponent gamma and Gruneisen constant gammaG, respectively. PMID- 25138258 TI - Reproductive interference between Rana dalmatina and Rana temporaria affects reproductive success in natural populations. AB - Experimental evidence suggests that reproductive interference between heterospecifics can seriously affect individual fitness; support from field studies for such an effect has, however, remained scarce. We studied reproductive interference in 25 natural breeding ponds in an area where two ranid frogs, Rana dalmatina and Rana temporaria, co-occur. The breeding seasons of the two species usually overlap and males of both species are often found in amplexus with heterospecific females, even though matings between heterospecifics produce no viable offspring. We estimated species abundance ratios based on the number of clutches laid and evaluated fertilization success. In ponds with low spatial complexity and a species abundance ratio biased towards R. temporaria, the average fertilization success of R. dalmatina eggs decreased, while this relationship was not detectable in spatially more complex ponds. Fertilization success of R. temporaria did not decrease with increasing relative numbers of heterospecifics. This asymmetry in fitness effects of reproductive interference may be attributed to R. temporaria males being more competitive in scramble competition for females than R. dalmatina males. Our study is among the first to demonstrate that in natural breeding populations of vertebrates interference among heterospecifics has the potential to substantially lower reproductive success at the population level, which may in turn affect population dynamics. PMID- 25138260 TI - Epidemiology of forearm fractures in adults in Denmark: national age- and gender specific incidence rates, ratio of forearm to hip fractures, and extent of surgical fracture repair in inpatients and outpatients. AB - National epidemiological studies of forearm fractures are scarce. We examined in- and outpatient rates in Denmark, including anatomical location, surgery, hospitalization ratio, recurrent fractures, and ratio of forearm to hip fractures. This may be useful for triangulation in countries with less detailed information. Rates were higher than previously estimated. INTRODUCTION: Despite a significant contribution to the overall burden of osteoporotic, nonvertebral fractures, relatively little information is available about age- and gender specific incidence rates for many countries including Denmark. METHODS: We used national individual patient data on inpatient and outpatient treatment to calculate rates of forearm fractures, taking readmissions into account, with subtables for distal and proximal fractures. We also calculated ratios of forearm to hip fractures that may be useful when imputing forearm fracture rates from other administrative sources. In addition, we report the rates of hospital admission and the rates of surgical treatment, allowing readers to extrapolate from the number of admissions or surgical procedures to incidence rates, should their data sources be less comprehensive. RESULTS: Forearm fracture rates were 278 per 100,000 patient years in men aged 50+ and 1,110 per 100,000 in women aged 50+. The female to male incidence rate ratio was 4.0 for the age group 50+ but close to unity in persons aged 40 or under. Two thirds of patients were treated on an outpatient basis with little difference across age and gender strata. Four out of five fractures were treated conservatively. The rate of forearm fractures in Denmark was somewhat higher in both genders than recently imputed from hip fracture rates and were close to the rates previously reported in studies from Norway and Sweden. CONCLUSION: The rates of forearm fracture in Denmark are higher than previously estimated and very similar to the high risk reported from studies in Norway and Sweden. PMID- 25138259 TI - Vitamin D and skeletal health in infancy and childhood. AB - During growth, severe vitamin D deficiency in childhood can result in symptomatic hypocalcaemia and rickets. Despite the suggestion from some studies of a secular increase in the incidence of rickets, this observation may be driven more by changes in population demographics than a true alteration to age, sex and ethnicity-specific incidence rates; indeed, rickets remains uncommon overall and is rarely seen in fair-skinned children. Additionally, the impact of less severe vitamin D deficiency and insufficiency has received much interest in recent years, and in this review, we consider the evidence relating vitamin D status to fracture risk and bone mineral density (BMD) in childhood and adolescence. We conclude that there is insufficient evidence to support the suggestion that low serum 25-hydroxyvitamin D [25(OH)D] increases childhood fracture risk. Overall, the relationship between 25(OH)D and BMD is inconsistent across studies and across skeletal sites within the same study; however, there is evidence to suggest that vitamin D supplementation in children with the lowest levels of 25(OH)D might improve BMD. High-quality randomised trials are now required to confirm this benefit. PMID- 25138262 TI - Serum levels of 25-hydroxyvitamin D and the occurrence of musculoskeletal diseases: a 3-year follow-up to the road study. AB - Assessment of serum 25-hydroxyvitamin D levels in association with the occurrence of musculoskeletal diseases using a population-based cohort study design revealed that serum 25-hydroxyvitamin D levels could predict the occurrence of osteoporosis at the femoral neck within 3 years, but not the occurrence of knee osteoarthritis or lumbar spondylosis. INTRODUCTION: The aim of this study is to clarify the association between serum 25-hydroxyvitamin D (25D) levels and occurrence of osteoporosis and osteoarthritis in the general population. METHODS: The Research on Osteoarthritis/Osteoporosis Against Disability study, a large scale population-based cohort study, was performed during 2005-2007. Serum 25D levels were measured in 1,683 participants. Of these, 1,384 individuals (81.9%) completed a second follow-up survey 3 years later. Osteoporosis was defined according to World Health Organization criteria, in which osteoporosis is diagnosed by T-scores of bone mineral density (BMD) that are 2.5 standard deviations (SD) less than normal BMD. Knee osteoarthritis and lumbar spondylosis were defined as Kellgren-Lawrence grade >=2, using paired X-ray films. Cumulative incidences were determined according to changes in measurements using World Health Organization criteria for osteoporosis or Kellgren-Lawrence grades for osteoarthritis between the baseline and second survey. RESULTS: The mean (SD) serum 25D level of the 1,384 participants in both surveys was 23.4 ng/mL (6.5). The annual cumulative incidences of osteoporosis at L2-4 and the femoral neck were 0.76 and 1.83%/year, respectively. The incidences of knee osteoarthritis and lumbar spondylosis were 3.3 and 11.4%/year, respectively. After adjusting for potential associated factors, logistic regression analyses revealed that the odds ratio for the occurrence of femoral neck osteoporosis significantly decreased as serum 25D levels increased (+1 SD; odds ratio 0.67; 95% confidence interval 0.49 0.92; p = 0.014). CONCLUSIONS: Higher serum 25D levels may prevent the occurrence of osteoporosis at the femoral neck, but not knee osteoarthritis, lumbar spondylosis, or osteoporosis at L2-4. PMID- 25138261 TI - A systematic review on the use of daily subcutaneous administration of teriparatide for treatment of patients with osteoporosis at high risk for fracture in Asia. AB - This systematic review aimed to examine the evidence for teriparatide in Asia for osteoporosis with a high fracture risk and for exploratory (unapproved) bone related indications. MEDLINE (1946+), EMBASE (1966+), and ClinicalTrials.gov (2008+) were searched (16 August 2013); all studies of daily subcutaneous teriparatide 20 MUg for bone-related conditions from China, Hong Kong, Japan, Republic of Korea, Philippines, Singapore, and Taiwan were included. Evidence on efficacy/safety was retrieved primarily from randomized controlled trials (10 publications) of postmenopausal women from Japan and China. In these studies, teriparatide was well tolerated; subjects had significantly greater increases in lumbar spine bone mineral density (BMD) from baseline compared with placebo, antiresorptive agents, or elcatonin/calcitonin; bone turnover markers increased from baseline and were sustained at elevated levels during teriparatide treatment. Few studies reported fracture risk, pain, or quality of life; one study showed a lower incidence of new-onset vertebral fracture with teriparatide versus antiresorptive agents. Nonrandomized studies (nine publications, one unpublished trial) conducted mainly in Taiwan, Japan, and the Republic of Korea provided supporting data for efficacy. The exploratory (unapproved) use of teriparatide (17 publications) for fracture healing and osteonecrosis of the jaw was described primarily in case reports. The clinical effectiveness of teriparatide for treatment of postmenopausal women with osteoporosis who are at high risk of fracture in Asia is focused primarily on improvements in BMD and tolerability. Recommended additional studies may include assessment of fracture risk and the effect of teriparatide on pain, quality of life, and mortality in Asia. PMID- 25138263 TI - Postpartum osteoporosis and vertebral fractures in two patients treated with enoxaparin during pregnancy. AB - Postpartum osteoporosis (PPO) is a rare disease associated with pregnancy and lactation period. Here, we report severe PPO and multiple vertebral compression fractures in two patients treated with enoxaparin--low-molecular-weight heparin (LMWH)--throughout their pregnancy. A 34-year-old woman who has delivered her second baby 3 months ago presented with severe low-back pain. She was treated with enoxaparin 40 mg/day for 8 months during her pregnancy. Dual-energy X-ray absorptiometry (DEXA) showed low T- and Z-scores in lumbar (L) vertebras. In magnetic resonance imaging (MRI), severe height losses in thoracic (T) 12, L1, and L2 vertebras were detected. She was diagnosed to have severe PPO and multiple vertebral compression fractures and was prescribed risedronate 35 mg/week, calcium, and vitamin D. The other patient was a 36-year-old woman diagnosed with PPO and vertebral fractures at the third week postpartum. She was also treated with enoxaparin 60 mg/day during her pregnancy. Severe osteoporosis in L vertebras and height losses indicative for compression fractures in T5-8, T11-12, and L2-5 vertebras were detected by DEXA and MRI, respectively. She was treated with calcitonin 200 U/day, calcium, and vitamin D. These findings suggest that vertebral compression fractures and PPO may be one of the causes of severe back pain in postpartum patients. Treatment with LMWH during pregnancy might be considered as a new risk factor for this rare condition. PMID- 25138264 TI - Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone mineral density at different skeletal sites in post-menopausal women. AB - Association between 22 single nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in 881 post-menopausal women. Our results suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. INTRODUCTION: The aim of this study was to assess the relationship of polymorphisms in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in a cohort of Chinese post-menopausal women. METHODS: A cross-sectional study was conducted in 881 post-menopausal women aged 50-89 years. All participants underwent lumbar spinal (LS) and femoral neck (FN) BMD evaluation by dual-energy X-ray absorptiometry. Twenty-two TNFSF11, TNFRSF11A, and TNFRSF11B SNPs were genotyped. We tested whether a single SNP or a haplotype was associated with BMD variations. RESULTS: Two SNPs in the TNFSF11 gene (rs2277439 and rs2324851) and one in the TNFRSF11A gene (rs7239261) were found to be significantly associated with FN BMD (p = 0.014, 0.013, and 0.047, respectively). Haplotype TGACGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was a genetic risk factor toward a lower FN BMD (beta = -0.1473; p = 0.01126). In contrary, haplotype TAGCGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287 rs9533166 was genetic protective factor for LS BMD (beta = 0.3923; p = 0.04917). CONCLUSIONS: Our findings suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. This contributes to the understanding of the role of genetic variation in this pathway in determining bone health. PMID- 25138266 TI - Basophil activation test in wasp venom allergy during mastocytosis. PMID- 25138265 TI - Effects of vitamin D supplementation on neuroplasticity in older adults: a double blinded, placebo-controlled randomised trial. AB - Vitamin D can improve muscle function and reduce falls, but whether it can strengthen neural connections within the brain and nervous system is not known. This 10-week randomised controlled trial indicates that treatment with 2,000 IU/day vitamin D3 does not significantly alter neuroplasticity relative to placebo in older adults. INTRODUCTION: The purpose of this study was to examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults. METHODS: This was a 10-week double-blinded, placebo-controlled randomised trial in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25-60 nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and paired-pulse transcranial magnetic stimulation applied over the motor cortex was used to assess changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as measures of corticospinal excitability and inhibition respectively, by recording electromyography (EMG) responses to stimulation from the wrist extensors. Changes in muscle strength, stair climbing power, gait (timed-up-and-go), dynamic balance (four square step test), serum 25(OH)D and BDNF concentrations were also measured. RESULTS: After 10 weeks, mean 25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no change in the placebo group. The vitamin D group experienced a significant 8-11% increase in muscle strength and a reduction in cortical excitability (MEP amplitude) and SICI relative to baseline (all P < 0.05), but these changes were not significantly different from placebo. There was no effect of vitamin D on muscle power, function or BDNF. CONCLUSIONS: Daily supplementation with 2,000 IU vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to placebo, but the finding that vitamin D treatment alone was associated with a decrease in corticospinal excitability and intracortical inhibition warrants further investigation as this suggests that it may improve the efficacy of neural transmission within the corticospinal pathway. PMID- 25138267 TI - beta-Glucosidase BGLU42 is a MYB72-dependent key regulator of rhizobacteria induced systemic resistance and modulates iron deficiency responses in Arabidopsis roots. AB - Selected soil-borne rhizobacteria can trigger an induced systemic resistance (ISR) that is effective against a broad spectrum of pathogens. In Arabidopsis thaliana, the root-specific transcription factor MYB72 is required for the onset of ISR, but is also associated with plant survival under conditions of iron deficiency. Here, we investigated the role of MYB72 in both processes. To identify MYB72 target genes, we analyzed the root transcriptomes of wild-type Col 0, mutant myb72 and complemented 35S:FLAG-MYB72/myb72 plants in response to ISR inducing Pseudomonas fluorescens WCS417. Five WCS417-inducible genes were misregulated in myb72 and complemented in 35S:FLAG-MYB72/myb72. Amongst these, we uncovered beta-glucosidase BGLU42 as a novel component of the ISR signaling pathway. Overexpression of BGLU42 resulted in constitutive disease resistance, whereas the bglu42 mutant was defective in ISR. Furthermore, we found 195 genes to be constitutively upregulated in MYB72-overexpressing roots in the absence of WCS417. Many of these encode enzymes involved in the production of iron mobilizing phenolic metabolites under conditions of iron deficiency. We provide evidence that BGLU42 is required for their release into the rhizosphere. Together, this work highlights a thus far unidentified link between the ability of beneficial rhizobacteria to stimulate systemic immunity and mechanisms induced by iron deficiency in host plants. PMID- 25138268 TI - Combined Y-shaped common channel transureteroureterostomy with Boari flap to treat bilateral long-segment ureteral strictures. AB - BACKGROUND: Ureteral stricture is a complication of several etiologies including idiopathic retroperitoneal fibrosis, infection, radiotherapy, instrumentation, and surgical procedures. A variety of techniques have been reported for management. The transureteroureterostomy and bladder flap have been the standard procedures for repairing distal ureteral defects of unilateral ureter. Bilateral ureteral stricture is an uncommon condition that challenges usual reconstructive procedures. It is a difficult task to reconstruct the complex situation of bilateral ureteral strictures. CASE PRESENTATION: A 54-year-old female underwent concurrent chemoradiotherapy for stage IVB squamous cell carcinoma of cervix. Subsequently, she had stricture of bilateral distal ureters with bilateral hydroureteronephrosis which was found by computed tomography. The renal function deteriorated during the follow-up period. She had periodic change of double-J stents and percutaneous nephrostomy. However, the renal function still deteriorated. We performed a combined Y-shaped common channel transureteroureterostomy with Boari flap to reconstruct bilateral long-segment ureteral strictures. The patient recovered uneventfully. CONCLUSION: Reconstruction of bilateral ureteral strictures is a difficult treatment. We developed a modified technique for the complex situation of bilateral ureteral strictures. To our knowledge, this has not been previously reported in the scientific literature and it is a feasible procedure to treat bilateral long segment ureteral strictures. PMID- 25138269 TI - Why did the proton cross the road? Humour and science communication. AB - The use of humour in public discourse about science has grown remarkably over the past few years, and when used in science communication activities is being seen as a great way to bring science to the public through laughter. However, barely any research has been published either on the often-assumed beneficial learning effects of humour in informal science education, or on the wider social functions and effects of humour about science and how humorous public discourse about science can influence the public understanding of science and the science-society relationship. This research note reviews some of the literature on the psychology and sociology of humour and comedy and tries to apply some of its insights to the effects humour might have when used in science communication. Although not intended to be anti-humour, this note attempts at least to start a more critical conversation on the value of humour in the communication of science. PMID- 25138270 TI - A first-principles investigation of the stabilities and electronic properties of SrZrO3 (1 1 0) (1 * 1) polar terminations. AB - The stabilities and electronic properties of SrZrO3 (1 1 0) (1 * 1) polar terminations were investigated systematically by the first-principles density functional theory method. Five possible polar surfaces, i.e. O-deficient, O-rich, stoichiometric, SrO-rich and SrO-deficient ones, were considered. The calculated results indicated that the charge neutralization and polarity compensation condition could be achieved by charge redistributions of surface atoms. For the O deficient (1 1 0) termination, some filled electronic states were separated from the original conduction bands, while a surface reconstruction was found for the O rich (1 1 0) surface. The remaining three (1 1 0) terminations remained insulated. Furthermore, a stability diagram involving seven different terminations was constructed using the surface grand potential technique, in which the effect of the chemical environment was included. The calculated results indicated that three (1 1 0) (O-rich, SrO-rich and stoichiometric) and 2 (0 0 1) (ZrO2 and SrO) terminations could be stabilized in distinct areas, whereas the O deficient surface was unstable within the whole region. Finally, we drew a comparison of stability behaviors between SrZrO3 (1 1 0) (1 * 1) polar surfaces and the counterparts of ATiO3 (A = Ba, Pb, Sr) and BaZrO3 materials. PMID- 25138271 TI - Extraprostatic extension (EPE) of prostatic carcinoma: is its proximity to the surgical margin or Gleason score important? AB - OBJECTIVE: To examine the association between histopathological factors of extraprostatic prostate cancer and outcome. PATIENTS AND METHODS: Patients with extraprostatic extension (EPE) without positive margins, seminal vesicle or lymph node involvement were analysed from a consecutive radical prostatectomy cohort of 1136 (2002-2006) for: (i) distance of EPE from the margin; (ii) Gleason score of the EPE; and (iii) extent of EPE. Log-rank, Kaplan-Meier, and Cox regression analyses were performed. RESULTS: The study included 194 pT3a, pN0, R0 patients with a median follow-up of 5.4 years, with 37 (19%) patients experiencing biochemical relapse (BCR). On univariable analysis, patients with a Gleason score of >=8 in the extraprostatic portion showed increased incidence of BCR compared with those with Gleason scores of <=7 (P = 0.03). The proximity of the EPE to the margin (0.01-7.5 mm) did not correlate with BCR. On multivariable analysis, the extent of EPE, the Gleason score of the dominant nodule or of the EPE portion did not correlate with BCR. CONCLUSION: Data from this study using current International Society of Urological Pathology Gleason scoring and EPE criteria indicate that close proximity of EPE to the margin is not associated with recurrence. Gleason score >=8 within EPE is associated with an increased BCR risk on univariable analysis, but larger studies are required to confirm whether extensive Gleason pattern 4 in an EPE indicates increased risk in an otherwise overall Gleason score 7 cancer. PMID- 25138272 TI - Etanercept restores normal insulin signal transduction in beta2-adrenergic receptor knockout mice. AB - BACKGROUND: Inhibition of TNFalpha protects the retina against diabetic-like changes in rodent models. The mechanism by which TNFalpha induces deleterious retinal changes is not known. Previously, we have shown that TNFalpha can inhibit normal insulin signal transduction, leading to increased apoptosis in both retinal endothelial cells (REC) and Muller cells. Additionally, beta2-adrenergic receptor knockout mice (beta2KO) have increased TNFalpha levels and decreased insulin receptor activity. In this study, we hypothesized that inhibition of TNFalpha in beta2KO mice would increase normal insulin signaling, leading to improved retinal function. METHODS: C57BL6 or beta2KO mice were left untreated or treated with etanercept (0.3 mg/kg subcutaneously, 3* a week) for 2 months. Electroretinogram analyses were done before treatment was initiated and after two months of treatment with etanercept on all mice. Western blot or ELISA analyses were done on whole retinal lysates from all four groups of mice for TNFalpha, suppressor of cytokine signaling 3 (SOCS3), insulin receptor, and apoptotic proteins. RESULTS: Etanercept significantly reduced TNFalpha levels in beta2KO mice, leading to increased insulin receptor phosphorylation on tyrosine 1150/1151. SOCS3 levels were increased in beta2KO mice, which were reduced after etanercept treatment. Pro-apoptotic proteins were reduced in etanercept-treated beta2KO mice. Etanercept improved ERG amplitudes in beta2KO mice. CONCLUSIONS: Inhibition of TNFalpha by etanercept protects the retina likely through reduced TNFalpha-mediated insulin resistance, leading to reduced apoptosis. PMID- 25138273 TI - Continuous transversus abdominis plane (TAP) blocks for postoperative pain control after hernia surgery: a randomized, triple-masked, placebo-controlled study. AB - BACKGROUND: Single-injection transversus abdominis plane (TAP) block provides postoperative analgesia and decreases supplemental analgesic requirements. However, there is currently no evidence from randomized, controlled studies investigating the possible benefits of continuous TAP blocks. Therefore, the aim of this randomized, triple-masked, placebo-controlled study was to determine if benefits are afforded by adding a multiple-day, ambulatory, continuous ropivacaine TAP block to a single-injection block following hernia surgery. METHODS: Preoperatively, subjects undergoing unilateral inguinal (N=19) or peri umbilical (N=1) hernia surgery received unilateral or bilateral TAP perineural catheter(s), respectively. All received a ropivacaine 0.5% (20 mL) bolus via the catheter(s). Subjects were randomized to either postoperative perineural ropivacaine 0.2% or normal saline using portable infusion pump(s). Subjects were discharged home where the catheter(s) were removed the evening of postoperative day (POD) 2. Subjects were contacted on POD 0-3. The primary endpoint was average pain with movement (scale: 0-10) queried on POD 1. RESULTS: Twenty subjects of a target 30 were enrolled due to the primary surgeon's unanticipated departure from the institution. Average pain queried on POD 1 for subjects receiving ropivacaine (N=10) was a mean (standard deviation) of 3.0 (2.6) vs 2.8 (2.7) for subjects receiving saline (N=10; 95% confidence interval difference in means -2.9 to 3.4; P=0.86). There were no statistically significant differences detected between treatment groups in any secondary endpoint. CONCLUSIONS: The results of this study do not support adding an ambulatory, continuous ropivacaine infusion to a single-injection ropivacaine TAP block for hernia surgery. However, the present investigation was underpowered, and further study is warranted. PMID- 25138276 TI - Highly oriented polymer semiconductor films compressed at the surface of ionic liquids for high-performance polymeric organic field-effect transistors. AB - A novel and versatile method to align polymer semiconductors is demonstrated. Spreading and subsequent mechanical compression of a polymer thin film on an ionic liquid's surface yield a polymer thin film that has high uniaxial orientation of the polymer backbone, which is tested for typical polymer semiconductors of PB16TTT, PNDTBTC20, and P3HT. TFTs fabricated by the method exhibit significantly higher mobility compared to TFTs fabricated using a conventional spin-coating process. PMID- 25138274 TI - Nuclear factor I-C (NFIC) regulates dentin sialophosphoprotein (DSPP) and E cadherin via control of Kruppel-like factor 4 (KLF4) during dentinogenesis. AB - Odontoblasts are a type of terminally differentiated matrix-secreting cells. A number of molecular mechanisms are involved in the differentiation of odontoblasts. Several studies demonstrated that Kruppel-like factor 4 (KLF4) promotes odontoblast differentiation via control of dentin sialophosphoprotein (DSPP). Because nuclear factor I-C (NFIC) is also known to control DSPP, we investigated the relationship between NFIC and KLF4 during odontoblast differentiation. Klf4 mRNA expression was significantly decreased in Nfic(-/-) pulp cells compared with wild type cells. In immunohistochemistry assays, dentin matrix protein 1 (Dmp1), and DSP protein expression was barely observed in Nfic( /-) odontoblasts and dentin matrix. Nfic bound directly to the Klf4 promoter and stimulated Klf4 transcriptional activity, thereby regulating Dmp1 and DSPP expression during odontoblast differentiation. Nfic or Klf4 overexpression promoted mineralized nodule formation in MDPC-23 cells. In addition, Nfic overexpression also decreased Slug luciferase activity but augmented E-cadherin promoter activity via up-regulation of Klf4 in odontoblasts. Our study reveals important signaling pathways during dentinogenesis: the Nfic-Klf4-Dmp1-Dspp and the Nfic-Klf4-E-cadherin pathways in odontoblasts. Our results indicate the important role of NFIC in regulating KLF4 during dentinogenesis. PMID- 25138277 TI - Agar-supported cultivation of Halorubrum sp. SSR, and production of halocin C8 on the scale-up prototype Platotex. AB - Halorubrum sp. SSR was isolated from a solar saltern in Algeria. The strain exhibited a high antibiotic activity against the indicator strain Natronorubrum aibiense G23, and the bioactive compound showed thermal, acid and alkali stability. SSR was grown on agar-supported cultivation (AgSF) to compare yields and applicability with traditional submerged cultivation. AgSF scale-up was implemented taking benefit from the solid-state cultivation prototype Platotex. This technology leads to high amounts of the target Halocin and facilitate the downstream steps. The antibiotic compound was purified according to a fast efficient procedure including ion exchange chromatography followed by a fractionation on C18 Sep-Pack cartridge. The compound was identified as Halocin C8 according to N-terminal amino acid sequencing and high-resolution mass spectrometry. PMID- 25138275 TI - Endogenous glucuronyltransferase activity of LARGE or LARGE2 required for functional modification of alpha-dystroglycan in cells and tissues. AB - Mutations in the LARGE gene have been identified in congenital muscular dystrophy (CMD) patients with brain abnormalities. Both LARGE and its paralog, LARGE2 (also referred to as GYLTL1B) are bifunctional glycosyltransferases with xylosyltransferase (Xyl-T) and glucuronyltransferase (GlcA-T) activities, and are capable of forming polymers consisting of [-3Xyl-alpha1,3GlcAbeta1-] repeats. LARGE-dependent modification of alpha-dystroglycan (alpha-DG) with these polysaccharides is essential for the ability of alpha-DG to act as a receptor for ligands in the extracellular matrix. Here we report on the endogenous enzymatic activities of LARGE and LARGE2 in mice and humans, using a newly developed assay for GlcA-T activity. We show that normal mouse and human cultured cells have endogenous LARGE GlcA-T, and that this activity is absent in cells from the Large(myd) (Large-deficient) mouse model of muscular dystrophy, as well as in cells from CMD patients with mutations in the LARGE gene. We also demonstrate that GlcA-T activity is significant in the brain, heart, and skeletal muscle of wild-type and Large2(-/-) mice, but negligible in the corresponding tissues of the Large(myd) mice. Notably, GlcA-T activity is substantial, though reduced, in the kidneys of both the Large(myd) and Large2(-/-) mice, consistent with the observation of alpha-DG/laminin binding in these contexts. This study is the first to test LARGE activity in samples as small as cryosections and, moreover, provides the first direct evidence that not only LARGE, but also LARGE2, is vital to effective functional modification of alpha-DG in vivo. PMID- 25138278 TI - Spatial distribution of diatom and cyanobacterial mats in the Dead Sea is determined by response to rapid salinity fluctuations. AB - Cyanobacteria and diatom mats are ubiquitous in hypersaline environments but have never been observed in the Dead Sea, one of the most hypersaline lakes on Earth. Here we report the discovery of phototrophic microbial mats at underwater freshwater seeps in the Dead Sea. These mats are either dominated by diatoms or unicellular cyanobacteria and are spatially separated. Using in situ and ex situ O2 microsensor measurements we show that these organisms are photosynthetically active in their natural habitat. The diatoms, which are phylogenetically associated to the Navicula genus, grew in culture at salinities up to 40 % Dead Sea water (DSW) (14 % total dissolved salts, TDS). The unicellular cyanobacteria belong to the extremely halotolerant Euhalothece genus and grew at salinities up to 70 % DSW (24.5 % TDS). As suggested by a variable O2 penetration depth measured in situ, the organisms are exposed to drastic salinity fluctuations ranging from brackish to DSW salinity within minutes to hours. We could demonstrate that both phototrophs are able to withstand such extreme short-term fluctuations. Nevertheless, while the diatoms recover better from rapid fluctuations, the cyanobacteria cope better with long-term exposure to DSW. We conclude that the main reason for the development of these microbial mats is a local dilution of the hypersaline Dead Sea to levels allowing growth. Their spatial distribution in the seeping areas is a result of different recovery rates from short or long-term fluctuation in salinity. PMID- 25138279 TI - The saci_2123 gene of the hyperthermoacidophile Sulfolobus acidocaldarius encodes an ATP-binding cassette multidrug transporter. AB - Multidrug resistance (MDR) transporters are capable of secreting structurally and functionally unrelated toxic compounds from the cell. Among this group are ATP binding cassette (ABC) transporters. These membrane proteins are typically arranged as either hetero- or homo-dimers of ABC half-transporters with each subunit consisting of a membrane domain fused at the C-terminus to an ATP-binding domain, or as full transporters in which the two subunits are fused into a single polypeptide. The saci_2123 gene of the thermoacidophilic archaeon Sulfolobus acidocaldarius is the only gene in the genome that encodes an ATP-binding cassette half-transporter, while a homologous gene is present in the genomes of S. solfataricus, S. tokodaii and S islandicus. Saci_2123 shares homology with well-characterized bacterial and mammalian MDR transporters. The saci_2132 gene is up-regulated when cells are exposed to drugs. A deletion mutant of saci_2132 was found to be more vulnerable to a set of toxic compounds, including detergents, antibiotics and uncouplers as compared to the wild-type strain, while the drug resistance could be restored through the plasmid-based expression of saci_2132. These data demonstrate that Saci_2132 is an archaeal ABC-MDR transporter and therefore it was termed Smr1 (Sulfolobus multidrug resistance transporter 1). PMID- 25138281 TI - Dual role of Tlx3 as modulator of Prrxl1 transcription and phosphorylation. AB - The proper establishment of the dorsal root ganglion/spinal cord nociceptive circuitry depends on a group of homeodomain transcription factors that includes Prrxl1, Brn3a and Tlx3. By the use of epistatic analysis, it was suggested that Tlx3 and Brn3a, which highly co-localize with Prrxl1 in these tissues, are required to maintain Prrxl1 expression. Here, we report two Tlx3-dependent transcriptional mechanisms acting on Prrxl1 alternative promoters, referred to as P3 and P1/P2 promoters. We demonstrate that (i) Tlx3 induces the transcriptional activity of the TATA-containing promoter P3 by directly binding to a bipartite DNA motif and (ii) it synergistically interacts with Prrxl1 by indirectly activating the Prrxl1 TATA-less promoters P1/P2 via the action of Brn3a. The Tlx3 N-terminal domain 1-38 was shown to have a major role on the overall Tlx3 transcriptional activity and the C-terminus domain (amino acids 256-291) to mediate the Tlx3 effect on promoters P1/P2. On the other hand, the 76-111 domain was shown to decrease Tlx3 activity on the TATA-promoter P3. In addition to its action on Prrxl1 alternative promoters, Tlx3 proved to have the ability to induce Prrxl1 phosphorylation. The Tlx3 domain responsible for Prrxl1 hyperphosphorylation was mapped and encompasses amino acid residues 76 to 111. Altogether, our results suggest that Tlx3 uses distinct mechanisms to tightly modulate Prrxl1 activity, either by controlling its transcriptional levels or by increasing Prrxl1 phosphorylation state. PMID- 25138282 TI - Enrichment options for African painted dogs (Lycaon pictus). AB - Best practices for carnivore enrichment encourage the diversity of species typical behaviors, increased activity, and reduced stereotypic behavior; ideally considering the life-history and behavior of each species. African wild dogs (Lycaon pictus), or painted dogs, are social carnivores that have large home ranges and complex pack dynamics (e.g., variation in group size, relatedness, etc.). As there are relatively few studies on painted dog enrichment, the goal of this study was to compile a list of enrichment options used by institutions participating in the species survival plan (SSP). Representatives were asked to describe social groups (n = 45), enclosures (n = 21), enrichment practices (options, delivery frequency, perceived success), and overall best practices. Respondents (61%, n = 23) reported using options for all six enrichment categories recommended by the Canid Taxon Advisory Group: environmental enrichment devices, habitat, sensory, food, behavioral, and social. Perceived success was significantly higher for the food category, followed by the sensory and behavioral categories. All respondents reported delivering enrichment at least multiple times a month, and most reported multiple times per week. Enclosure size did not differ significantly for mixed-sex groups (n = 28) compared to single-sex groups (n = 17). We discuss respondents' suggestions for best practices and the need to record data to compare perceived success with actual behavioral effects, controlling for variation in group size and composition. Overall, respondents recommended a flexible approach, since not all painted dogs and groups respond in the same way to the enrichment options. PMID- 25138284 TI - Scandium carbide/cyanide alloyed cluster inside fullerene cage: synthesis and structural studies of Sc3(MU3-C2)(MU3-CN)@Ih-C80. AB - A new Sc3(C2)(CN)@Ih-C80 metallofullerene encaging a scandium carbide/cyanide alloyed cluster was prepared and investigated. Sc3(C2)(CN)@Ih-C80 was synthesized by the arc-discharging method and isolated by HPLC. Its experimental (13)C NMR spectrum with two signals clearly confirms an icosahedral C80 cage, and theoretically calculated (13)C NMR peaks agree well with the experimental results. Further, theoretical calculations disclosed that the endohedral MU3-C2 and MU3-CN moieties are situated on each side of the triangular shaped Sc3 unit to form a scandium carbide/cyanide alloyed cluster. Kohn-Sham molecular orbitals reveals the electronic structure of (Sc(3+))3(C2)(2-)(CN)(-)@C80(6-), in which two anions, MU3-C2(2-) and MU3-(CN)(-), construct and stabilize this special molecule together. The FTIR and Raman spectra of Sc3(C2)(CN)@Ih-C80 were analyzed by comparison of the experimental and calculated results to further confirm its structure and to uncover cluster-based vibrational modes. PMID- 25138283 TI - Double-clicking peptides onto phosphorothioate oligonucleotides: combining two proapoptotic agents in one molecule. AB - Described here is a method for the conjugation of phosphorothioate oligonucleotides (PSOs) with peptides. PSOs are key to antisense technology. Peptide-PSO conjugates may improve target specificity, tissue distribution, and cellular uptake of PSOs. However, the highly nucleophilic phosphorothioate structure poses a challenge to conjugation chemistry. Herein, we introduce a new method which involves a sequence of oxime ligation and strain-promoted [2+3] cycloaddition. The usefulness of the method was demonstrated in the synthesis of peptide-PSO conjugates that targeted two suppressors of both the intrinsic and the extrinsic pathway of apoptosis. It is shown that the activity of a PSO sequence targeted against mRNA from c-Flip can be enhanced by conjugation with a peptide mimetic designed to inhibit the X-linked inhibitor of apoptosis protein (XIAP). PMID- 25138285 TI - Neuroimaging features in C9orf72 and TARDBP double mutation with FTD phenotype. AB - Increasing evidence has shown that morphological and functional neuroimaging may help to understand the pathophysiological mechanisms leading to behavioral disturbances in patients with genetic or sporadic frontotemporal dementia (FTD). The C9orf72 expansion was found in association with the N267S TARDBP mutation in two siblings with behavioral-variant FTD (bvFTD). In one of them with very mild dementia, MRI showed symmetric atrophy of temporal, inferolateral and orbital frontal cortex, while [18F]FDG-PET disclosed more extended hypometabolism in dorsolateral and inferolateral frontal cortex, anterior cingulate, and caudate nucleus. Hypometabolism in right lateral and orbital frontal cortex was confirmed also in comparison with a group of sporadic bvFTD patients. These findings appear as the neuroimaging hallmark of double C9orf72 and TARDBP gene mutation with a bvFTD phenotype. PMID- 25138280 TI - The chicken chorioallantoic membrane model in biology, medicine and bioengineering. AB - The chicken chorioallantoic membrane (CAM) is a simple, highly vascularized extraembryonic membrane, which performs multiple functions during embryonic development, including but not restricted to gas exchange. Over the last two decades, interest in the CAM as a robust experimental platform to study blood vessels has been shared by specialists working in bioengineering, development, morphology, biochemistry, transplant biology, cancer research and drug development. The tissue composition and accessibility of the CAM for experimental manipulation, makes it an attractive preclinical in vivo model for drug screening and/or for studies of vascular growth. In this article we provide a detailed review of the use of the CAM to study vascular biology and response of blood vessels to a variety of agonists. We also present distinct cultivation protocols discussing their advantages and limitations and provide a summarized update on the use of the CAM in vascular imaging, drug delivery, pharmacokinetics and toxicology. PMID- 25138286 TI - Importance of branched-chain amino acids in patients with liver cirrhosis and advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy. AB - PURPOSE: The aim of this retrospective cohort study was to clarify the effect of a branched-chain amino acids (BCAA) on the liver function and the prognosis of Child-Pugh class (C-P) A and B liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) undergoing hepatic arterial infusion chemotherapy (HAIC). METHODS: Ninety-two adult Japanese patients with LC and aHCC underwent HAIC. They were in C-P A or B, and they showed multiple partial responses or stable disease. We excluded 11 patients classified as C-P C and 47 patients who showed no response. The patients were divided into an HAIC group receiving HAIC alone (n = 43) and a BCAA group treated with HAIC plus BCAA (n = 49). HAIC was delivered via the proper hepatic artery. The BCAA group also received oral administration of BCAA. RESULTS: In the BCAA group, serum albumin increased significantly after HAIC, while there were no significant changes in serum total bilirubin, serum aminotransferases, prothrombin time, ascites, and hepatic encephalopathy. The C-P score decreased significantly after HAIC compared with before HAIC in C-P B patients, although there was no significant change in C-P A patients. Survival of the BCAA group was significantly longer than that of the HAIC group, with the median survival time being 426 versus 272 days for C-P B patients, although there was no significant difference for C-P A patients. CONCLUSIONS: Branched-chain amino acids might improve the survival and C-P score by increasing serum albumin in C-P B patients with aHCC receiving HAIC. PMID- 25138288 TI - Yb/Er co-doped phosphate all-solid single-mode photonic crystal fiber. AB - An all-solid Yb(3+)/Er(3+) co-doped single-mode phosphate photonic crystal fiber (PCF) with Watt-level output power and 20 MUm core diameter is demonstrated for the first time. A PCF whose refractivity of the active core is lower than that of the background glass is suggested and theoretically confirmed to be in single mode operation at 40 MUm core diameter. PMID- 25138287 TI - Patterns of change in implementation of state alcohol control policies in the United States, 1999-2011. AB - AIMS: To examine state alcohol control policy implementation by policy efficacy and intent. DESIGN: A descriptive longitudinal analysis of policy implementation. SETTING: The United States, 1999-2011. PARTICIPANTS: Fifty states and the District of Columbia. MEASUREMENTS: Twenty-nine state-level policies were rated based on an implementation rating (IR; range = 0.0-1.0) gathered from the Alcohol Policy Information System, government and industry reports and other sources; and expert judgment about policy efficacy for addressing binge drinking and alcohol impaired driving among the general population and youth, respectively. FINDINGS: On average, implementation of the most effective general population policies did not change [mean IR = 0.366 in 1999; 0.375 in 2011; slope for annual change = 0.001; 95% confidence interval (CI) for the slope -0.001, 0.002]. In contrast, implementation increased over time for less effective policies (mean IR = 0.287 in 1999; 0.427 in 2011; slope for annual change compared with most effective policies = 0.009; slope 95% CI = 0.002-0.007), for youth-oriented policies (mean IR = 0.424 in 1999; 0.511 in 2011; slope for annual change compared with most effective policies = 0.007; slope 95% CI = 0.005-0.009), and for impaired driving policies (mean IR = 0.493 in 1999; 0.608 in 2011; slope for annual change compared with most effective policies = 0.0105; slope 95% CI = 0.007-0.014). CONCLUSIONS: Implementation of politically palatable state alcohol policies, such as those targeting youth and alcohol-impaired driving, and less effective policies increased during 1999-2011 in the United States, while the most effective policies that may maximally protect public health remained underused. PMID- 25138290 TI - Evaluation and validation of a serum bactericidal antibody assay for Haemophilus influenzae type b and the threshold of protection. AB - Prior to routine immunisation, Haemophilus influenzae serotype b (Hib) was a major cause of serious bacterial infections, particularly in young children. In the United Kingdom, introduction of the Hib conjugate vaccine into the national childhood immunisation schedule has led to a sustained decline in invasive Hib disease across all age-groups. Evaluation of the immune response to Hib conjugate vaccines involves measurement of serum IgG antibodies against the capsular polyribosyl-ribitol-phosphate (PRP) polysaccharide by enzyme-linked immunosorbent assay (ELISA), with accepted short-term and long-term protective thresholds of >=0.15MUg/mL and >=1.0MUg/mL, respectively. These levels were derived by passive immunisation or immunisation with pure polysaccharide, and their relevance for protection following immunisation with conjugate vaccines remains unclear. This study aimed to modify and optimise a serum bactericidal antibody (SBA) assay to evaluate the functional activity of Hib antibodies generated following Hib conjugate vaccination. Validation of the Hib SBA assay was deemed acceptable for all assay parameters tested. A strong correlation between anti-PRP IgG concentrations and SBA titres was observed in vaccinated adults (r=0.81), as well as infants after primary immunisation at 2, 3, and 4 months (r=0.635) and after the 12-month booster (r=0.746). The assay identified some children with high anti PRP IgG but low SBA activity and vice versa. The predictive protective SBA titre corresponding to a post-booster anti-PRP IgG of 1.0MUg/mL was 8. Thus, the optimised Hib SBA assay was specific and reproducible and correlated with anti PRP IgG. Such assays may have a role in evaluating immune responses to conjugate vaccines in addition to measuring capsular antibodies. PMID- 25138291 TI - Development of a BCG challenge model for the testing of vaccine candidates against tuberculosis in cattle. AB - Vaccination is being considered as part of a sustainable strategy for the control of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle against BTB. However, BCG confers partial protection against BTB and therefore, there is a need to develop improved vaccines. BTB vaccine efficacy experiments require the use of biosafety level 3 facilities which are expensive to maintain, generally oversubscribed and represent a bottle neck for the testing of vaccine candidates. One indicator of the induction of protective responses would be the ability of the host's immune response to control/kill mycobacteria. In this work we have evaluated an intranodal BCG challenge for the selection of vaccine candidates at biosafety level 2 which are capable of inducing mycobactericidal responses. To our knowledge, this is the first such report. Whilst BCG only confers partial protection, it is still the standard against which other vaccines are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu counts than naive cattle at 14 and 21 days after intranodal challenge with BCG (Tokyo strain). This model could help prioritize competing TB vaccine candidates and exploration of primary and secondary immune responses to mycobacteria. PMID- 25138295 TI - Resumption of work after acute coronary syndrome or coronary artery bypass surgery. PMID- 25138292 TI - Rethinking cumulative exposure in epidemiology, again. AB - The use of cumulative exposure, the product of intensity and duration, has enjoyed great popularity in epidemiology of chronic diseases despite numerous known caveats in its interpretation. We briefly review the history of use of cumulative exposure in epidemiology and propose an alternative method for relating time-integrated exposures to health risks. We argue, as others before us have, that cumulative exposure metrics obscures the interplay of exposure intensity and duration. We propose to use a computationally simple alternative in which duration and intensity of exposure are modelled as a main effect and their interaction, cumulative exposure, only be added if there is evidence of deviation from this additive model. We also consider the Lubin-Caporaso model of interplay of exposure intensity and duration. The impact of measurement error in intensity on model selection was also examined. The value of this conceptualization is demonstrated using a simulation study and further illustrated in the context of respiratory health and occupational exposure to latex dust. We demonstrate why cumulative exposure has been so popular because the cumulative exposure metric per se gives a robust answer to the existence of an association, regardless of the underlying true mechanism of disease. Treating cumulative exposure as the interaction of main effects of exposure duration and intensity enables epidemiologists to derive more information about mechanism of disease then fitting cumulative exposure metric by itself, and without the need to collect additional data. We propose that the practice of fitting duration, intensity and cumulative exposure separately to epidemiologic data should lead to conceptualization of cumulative exposure as interaction of main effects of duration and intensity of exposure. PMID- 25138293 TI - Impact of ambient fine particulate matter carbon measurement methods on observed associations with acute cardiorespiratory morbidity. AB - Elemental carbon (EC) and organic carbon (OC) represent a substantial portion of particulate matter <2.5 MUm in diameter (PM2.5), and have been associated with adverse health effects. EC and OC are commonly measured using the National Institute of Occupational Safety and Health (NIOSH) method or the Interagency Monitoring of Protected Visual Environments (IMPROVE) method. Measurement method differences could have an impact on observed epidemiologic associations. Daily speciated PM2.5 data were obtained from the St Louis-Midwest Supersite, and St Louis emergency department (ED) visit data were obtained from the Missouri Hospital Association for the period June 2001 to April 2003. We assessed acute associations between cardiorespiratory ED visits and EC and OC from NIOSH and IMPROVE methods using Poisson generalized linear models controlling for temporal trends and meteorology. Associations were generally similar for EC and OC from the different measurement methods. The most notable difference between methods was observed for congestive heart failure and EC (for example, warm season rate ratios (95% confidence intervals) per interquartile range change in EC concentration were: NIOSH=1.06 (0.99-1.13), IMPROVE=1.01 (0.96-1.07)). Overall, carbon measurement method had little impact on acute associations between EC, OC, and ED visits. Some specific differences were observed, however, which may be related to particle composition. PMID- 25138294 TI - Cow allergen (Bos d2) and endotoxin concentrations are higher in the settled dust of homes proximate to industrial-scale dairy operations. AB - Airborne contaminants produced by industrial agricultural facilities contain chemical and biological compounds that can impact the health of residents living in close proximity. Settled dust can be a reservoir for these contaminants and can influence long-term exposures. In this study, we sampled the indoor- and outdoor-settled dust from 40 homes that varied in proximity to industrial-scale dairies (ISD; industrial-scale dairy, a term used in this paper to describe a large dairy farm and adjacent waste sprayfields, concentrated animal feeding operation or animal feeding operation, that uses industrial processes) in the Yakima Valley, Washington. We analyzed settled dust samples for cow allergen (Bos d2, a cow allergen associated with dander, hair, sweat and urine, it is a member of the lipocalin family of allergens associated with mammals), mouse allergen (Mus m1; major mouse allergen, a mouse urinary allergen, in the lipocalin family), dust mite allergens (Der p1 (Dermatophagoides pteronissinus 1) and Der f1 (Dermatophagoides farinae 1)), and endotoxin (a component of the cell walls of gram negative bacteria, lipopolysaccharide, which can be found in air and dust and can produce a strong inflammatory response). A concentration gradient was observed for Bos d2 and endotoxin measured in outdoor-settled dust samples based on proximity to ISD. Indoor-settled dust concentrations of Bos d2 and endotoxin were also highest in proximal homes. While the associated health effects of exposure to cow allergen in settled dust is unknown, endotoxin at concentrations observed in these proximal homes (100 EU/mg) has been associated with increased negative respiratory health effects. These findings document that biological contaminants emitted from ISDs are elevated in indoor- and outdoor-settled dust samples at homes close to these facilities and extend to as much as three miles (4.8 km) away. PMID- 25138296 TI - Primary central nervous system lymphoma in the elderly. PMID- 25138297 TI - Prognosis factors in Japanese elderly patients with primary central nervous system lymphoma treated with a nonradiation, intermediate-dose methotrexate containing regimen. AB - BACKGROUND: Nearly half of all patients with primary central nervous system lymphoma (PCNSL) are known to be aged over 60 years. However, clinical factors affecting treatment outcomes in elderly patients are understudied. METHODS: We analyzed 38 patients with PCNSL older than 60 years. All patients were treated with a nonradiation, intermediate-dose methotrexate-containing regimen between March 2005 and May 2013 at the University of Tsukuba Hospital. RESULTS: The 3 year overall survival and progression-free survival rates were 56.2% (95% confidence interval (CI) 36.2-76.2%) and 29.8% (95% CI 9-50.6%), respectively, with a median follow-up of 36.5 months. We found that an age > 75 years, a Karnofsky performance score < 70, altered mentation, and a creatinine clearance (CrCl) > 90 ml/min were significant (p < 0.05) factors associated with a worse survival, by univariate analysis. Multivariate analysis revealed that CrCl (p < 0.05; hazard ratio (HR) = 3.39; 95% CI 1.08-10.68) and altered mentation (p < 0.05; HR = 6.27; 95%CI 1.37-28.83) were independent significant association factors. The most frequent adverse event was myelosuppression, with grade 3-4 hematologic toxicities in 28 patients. No delayed neurotoxicities were observed. CONCLUSION: More intensive therapy may be introduced in selected patients with poor prognosis factors to improve outcomes. PMID- 25138298 TI - Distress in cancer patients and their caregivers and association with the caregivers' perception of dyadic communication. AB - BACKGROUND: Discrepancies within cancer-affected couples can disrupt security within the dyadic relationship during cancer treatment. This study investigated the patients' and caregivers' distress and associations between the caregivers' perception of the patients' degree of open communication and their distress. PARTICIPANTS AND METHODS: In a cross-sectional survey, 189 pairs of cancer patients (31% gastrointestinal, 34% lung, 35% urological cancers) and their partners were assessed for distress (QSC-R10), depression and anxiety (PHQ-2/GAD 2). The caregivers also reported their perception of the patients' degree of disclosure regarding cancer-relevant topics (CCAT-F Disclosure subscale), caregiver strain (CSI), and unmet needs (SCNS-P&C). Prevalences of clinically significant distress were calculated. Associations were calculated between the caregivers' and the patients' ratings and between the caregivers' distress and their perception of the patients' degree of disclosure. RESULTS: 33% of the caregivers and 25% of the patients exhibited significant anxiety, with a tendency towards a higher frequency in the caregivers (p = 0.10). The prevalence of depression was lower but equally high in caregivers and patients. The caregivers' perceived non-disclosure by the patients was primarily associated with their anxiety (r = 0.31), disease-specific distress (r = 0.32), and psychological/emotional needs (r = 0.35). CONCLUSION: The identification of caregivers reporting problems in communicating with patients should be pursued in clinical practice as this might indicate that caregivers are particularly burdened. PMID- 25138299 TI - Thymic epithelial tumors: analysis of prognostic factors with emphasis on the role of adjuvant radiation therapy. AB - BACKGROUND: The prognostic impacts of histopathological classification, Masaoka staging system, extent of surgery, and adjuvant treatment approaches in thymic epithelial tumors (TETs) were investigated. MATERIAL AND METHODS: Records of 22 patients were retrospectively reviewed. Total thymectomy was performed on 5 patients and thymectomy on 17. Complete resection was achieved for 14 patients. Radiation therapy (RT) was considered for all patients with stage III or IV disease and all patients undergoing incomplete resections. RESULTS: Local control had been achieved in all patients and all were alive with no evidence of disease (ANED) at 0.2-7.8 years (median, 2.3 years). Of 4 patients with stage II disease, 2 (favorable group) had undergone complete resections and 2 (intermediate group) had undergone incomplete resections. Those undergoing incomplete resections had received RT. Of these 4 patients, all were ANED. All 4 patients with Masaoka stage III disease that were involved in the study had undergone incomplete resections and had received RT. Also, these patients were ANED. CONCLUSIONS: Patients with TETs undergoing less than complete resections might be referred for RT in the postoperative setting, while the role of RT in patients undergoing complete resections remains unclear. PMID- 25138300 TI - Staging of primary breast cancer is not indicated in asymptomatic patients with early tumor stages. AB - BACKGROUND: The routinely practiced staging for distant metastasis in patients with primary breast cancer has been increasingly questioned. PATIENTS AND METHODS: Data from 742 patients with breast cancer who had completed staging (chest x-ray, liver ultrasound, and bone scan) were retrospectively analyzed. Present findings were transferred to a dataset of a voluntarily monitored benchmarking project by the West German Breast Center that included patient data of 179 breast cancer centers. RESULTS: Routine staging examinations revealed in 1.2% (n = 9) distant metastasis and in 38.8% (n = 288) suspicious results. In total, 15 patients (2%) had distant metastases confirmed by additional diagnostics. The existence of distant metastases correlated with tumor size, nodal state, and lymphatic vessel spread. Tumor size and nodal state were independent predictors for disseminated disease. The risk of exhibiting distant metastases was 0.77% for patients with tumor stage pT1 pN1. Based on these findings, in 159,310 patients 41,728 chest x-rays, 43,950 liver ultrasounds, and 39,037 bone scans could have been avoided. CONCLUSION: Asymptomatic patients with tumor stages <= pT1 pN1 do not benefit from staging of primary breast cancer. Suspending staging examinations for these patients could reduce cost without restricting oncologic safety. PMID- 25138301 TI - Meta-analyses of the effect of CYP1A1 and CYP2D6 polymorphisms on the risk of head and neck squamous cell carcinoma. AB - BACKGROUND: CYP1A1 and CYP2D6 are important genes encoding enzymes involved in the metabolism of toxic chemicals and carcinogens. However, inconclusive results for the association between CYP1A1 and CYP2D6 polymorphisms and the risk of head and neck squamous cell carcinoma (HNSCC) have been reported. We conducted a meta analysis to evaluate the association of CYP1A1 and CYP2D6 polymorphisms with the risk of HNSCC. METHODS: A database search yielded 19 relevant studies. 3 polymorphisms were included in the meta-analysis: CYP1A1, CYP2D6*4 and CYP2D6*10. Random or fixed effect models were used in the analysis. RESULTS: The CYP1A1 polymorphism was associated with HNSCC (for m1m1 vs. m1m2: odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.030-1.542, pheterogeneity = 0.025; for the recessive model: OR = 1.316, 95% CI = 1.065-1.625, pheterogeneity = 0.001). The analysis showed evidence for association between the CYP2D6*4 polymorphism and HNSCC in Asian populations; however, negative results were also observed in other models. A significant association was also observed between CYP2D6*10 polymorphism and HNSCC risk. CONCLUSIONS: The current study demonstrates that the CYP1A1 and CYP2D6 polymorphisms are associated with susceptibility to both development and progression of HNSCC. PMID- 25138302 TI - CyberKnife Treatment for Kaposiform Hemangioendothelioma of the Ilium in an adult: case report and review of the literature. AB - BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that mainly affects infants. KHE rarely develops in adolescents and adults. These tumors tend to be locally invasive, but are not known to produce distant metastases. Numerous treatment modalities are available for KHE, but the optimal therapy is unknown. CASE REPORT: A 51-year-old woman was diagnosed with KHE of the ilium in September 2005. The lesion recurred within 5 years of local excision, and was subsequently treated with CyberKnife. Within 1 month of CyberKnife therapy, pain intensity was significantly reduced and the patient's quality of life was significantly improved. Since January 2011, she has remained pain-free and has had no signs of recurrence or metastasis for more than 2 years following CyberKnife therapy. CONCLUSION: We report the first CyberKnife treatment of an adult with KHE of the bone without accompanying cutaneous changes and Kasabach-Merritt syndrome. CyberKnife treatment could be a useful temporizing measure for bone KHE. PMID- 25138303 TI - DNA repair gene--XRCC1 in relation to genome instability and role in colorectal carcinogenesis. AB - Colorectal carcinogenesis is a multifactorial and multi-gene process, involving 3 major genetic instability pathways: chromosomal instability, microsatellite instability and CpG island methylator phenotype. Inefficient DNA repair is one of the causes of genetic instability leading to tumorigenesis. Defects in DNA repair genes are associated with cancer development. The XRCC1 gene is an important DNA repair genes and forms the component of several different damage recovery pathways, including base excision repair and single-strand breaks repair - the processes frequently involved in cancer transformation. In this review we have shed light on the structure and functioning of the XRCC1 gene and its protein, and the role played by XRCC1 in colorectal carcinogenesis. PMID- 25138304 TI - PAPST1 regulates sulfation of heparan sulfate proteoglycans in epithelial MDCK II cells. AB - Proteoglycan (PG) sulfation depends on activated nucleotide sulfate, 3' phosphoadenosine-5'-phosphosulfate (PAPS). Transporters in the Golgi membrane translocate PAPS from the cytoplasm into the organelle lumen where PG sulfation occurs. Silencing of PAPS transporter (PAPST) 1 in epithelial MDCK cells reduced PAPS uptake into Golgi vesicles. Surprisingly, at the same time sulfation of heparan sulfate (HS) was stimulated. The effect was pathway specific in polarized epithelial cells. Basolaterally secreted proteoglycans (PGs) displayed an altered HS sulfation pattern and increased growth factor binding capacity. In contrast, the sulfation pattern of apically secreted PGs was unchanged while the secretion was reduced. Regulation of PAPST1 allows epithelial cells to prioritize between PG sulfation in the apical and basolateral secretory routes at the level of the Golgi apparatus. This provides sulfation patterns that ensure PG functions at the extracellular level, such as growth factor binding. PMID- 25138306 TI - Theoretical study of enzymatic catalysis explains why the trapped covalent intermediate in the E303C mutant of glycosyltransferase GTB was not detected in the wild-type enzyme. AB - Hybrid quantum mechanics/molecular mechanics calculations were used to study the catalytic mechanism of the retaining human alpha-(1,3)-galactosyltransferase (GTBWT) and its E303C mutant (GTBE303C). Both backside (via covalent glycosyl enzyme intermediate, CGEI) and frontside SNi-like mechanisms (via oxocarbenium ion intermediate, OCII) were investigated. The calculations suggest that both mechanisms are feasible in the enzymatic catalysis. The nucleophilic attack of the acceptor substrate to the anomeric carbon of OCII is the rate-determining step with an overall reaction barrier (DeltaE(?) = 19.5 kcal mol(-1)) in agreement with an experimental rate constant (kcat = 5.1 s(-1)). A calculated alpha-secondary kinetic isotope effect (alpha-KIE) of 1.27 (GTBWT) and 1.26 (GTBE303C) predicts dissociative character of the transition state in agreement with experimentally measured alpha-KIE of other retaining glycosyltransferases. Remarkably, stable CGEI in GTBE303C compared with its counterpart in GTBWT may explain why the CGEI has been detected by mass spectrometry only in GTBE303C ( Soya N, Fang Y, Palcic MM, Klassen JS. 2011. Trapping and characterization of covalent intermediates of mutant retaining glycosyltransferases. Glycobiology, 21: 547-552). PMID- 25138305 TI - Galectin-3 in angiogenesis and metastasis. AB - Galectin-3 is a member of the family of beta-galactoside-binding lectins characterized by evolutionarily conserved sequences defined by structural similarities in their carbohydrate-recognition domains. Galectin-3 is a unique, chimeric protein consisting of three distinct structural motifs: (i) a short NH2 terminal domain containing a serine phosphorylation site; (ii) a repetitive proline-rich collagen-alpha-like sequence cleavable by matrix metalloproteases; and (iii) a globular COOH-terminal domain containing a carbohydrate-binding motif and an NWGR anti-death motif. It is ubiquitously expressed and has diverse biological functions depending on its subcellular localization. Galectin-3 is mainly found in the cytoplasm, also seen in the nucleus and can be secreted by non-classical, secretory pathways. In general, secreted galectin-3 mediates cell migration, cell adhesion and cell-cell interactions through the binding with high affinity to galactose-containing glycoproteins on the cell surface. Cytoplasmic galectin-3 exhibits anti-apoptotic activity and regulates several signal transduction pathways, whereas nuclear galectin-3 has been associated with pre mRNA splicing and gene expression. Its unique chimeric structure enables it to interact with a plethora of ligands and modulate diverse functions such as cell growth, adhesion, migration, invasion, angiogenesis, immune function, apoptosis and endocytosis emphasizing its significance in the process of tumor progression. In this review, we have focused on the role of galectin-3 in tumor metastasis with special emphasis on angiogenesis. PMID- 25138307 TI - Residents' and preceptors' perceptions of the use of the iPad for clinical teaching in a family medicine residency program. AB - BACKGROUND: As Family Medicine programs across Canada are transitioning into a competency-based curriculum, medical students and clinical teachers are increasingly incorporating tablet computers in their work and educational activities. The purpose of this pilot study was to identify how preceptors and residents use tablet computers to implement and adopt a new family medicine curriculum and to evaluate how they access applications (apps) through their tablet in an effort to support and enhance effective teaching and learning. METHODS: Residents and preceptors (n = 25) from the Family Medicine program working at the Pembroke Regional Hospital in Ontario, Canada, were given iPads and training on how to use the device in clinical teaching and learning activities and how to access the online curriculum. Data regarding the use and perceived contribution of the iPads were collected through surveys and focus groups. This mixed methods research used analysis of survey responses to support the selection of questions for focus groups. RESULTS: Reported results were categorized into: curriculum and assessment; ease of use; portability; apps and resources; and perceptions about the use of the iPad in teaching/learning setting. Most participants agreed on the importance of accessing curriculum resources through the iPad but recognized that these required enhancements to facilitate use. The iPad was considered to be more useful for activities involving output of information than for input. Participants' responses regarding the ease of use of mobile technology were heterogeneous due to the diversity of computer proficiency across users. Residents had a slightly more favorable opinion regarding the iPad's contribution to teaching/learning compared to preceptors. CONCLUSIONS: iPad's interface should be fully enhanced to allow easy access to online curriculum and its built-in resources. The differences in computer proficiency level among users should be reduced by sharing knowledge through workshops led by more skillful iPad users. To facilitate collection of information through the iPad, the design of electronic data-input forms should consider the participants' reported negative perceptions towards typing data through mobile devices. Technology deployment projects should gather sufficient evidence from pilot studies in order to guide efforts to adapt resources and infrastructure to relevant needs of Family Medicine teachers and learners. PMID- 25138308 TI - Diglycerol-based polyesters: melt polymerization with hydrophobic anhydrides. AB - The melt polymerization of diglycerol with bicyclic anhydride monomers derived from a naturally occurring monoterpene provides an avenue for polyesters with a high degree of sustainability. The hydrophobic anhydrides are synthesized at ambient temperature via a solvent-free Diels-Alder reaction of alpha-phellandrene with maleic anhydride. Subsequent melt polymerizations with tetra-functional diglycerol are effective under a range of [diglycerol]/[anhydride] ratios. The hydrophobicity of alpha-phellandrene directly impacts the swelling behavior of the resulting polyesters. The low E factors (<2), large amount of bio-based content (>75%), ambient temperature monomer synthesis, and polymer degradability represent key factors in the design of these sustainable polyesters. PMID- 25138309 TI - Prevalence of methicillin-resistant Staphylococcus aureus : effect of different criteria for elimination of duplicates. AB - BACKGROUND: The purpose of this study is to compare the effect of different systems for eliminating duplicates in order to optimize the calculation of the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: We compare the Clinical and Laboratory Standards Institute (CLSI) criterion, time criteria and the criterion recommended by the European Antimicrobial Surveillance System (EARSS). RESULTS: Multiple isolates of MRSA are frequently recovered from successive cultures from the same patient (the average isolation rate of MRSA is 2.72), which demonstrates the importance of eliminating duplicates. When CLSI criterion data are compared to those obtained using other criteria, a significant increase in the number of S. aureus isolates was found applying time criteria (up to 36%) or the EARSS criterion (13%). There is also an increase in the methicillin resistance rate (between 3.31 and 3.96%; p < 0.01). CONCLUSIONS: We believe that the EARSS method, with the proper quality controls and latest software tools available, is the best for determining the true situation of MRSA. PMID- 25138310 TI - Circulating mRNA for the PLAC1 gene as a second trimester marker (14-18 weeks' gestation) in the screening for late preeclampsia. AB - OBJECTIVE: To develop a model for prediction of late preeclampsia (PE; which develops at or after 34 weeks' gestation) based on maternal history and characteristics, mean arterial pressure (MAP), and circulating levels of mRNA for the placenta-specific 1 (PLAC1) gene in maternal plasma at 14-18 weeks' gestation. METHOD: This was a screening study of singleton pregnancies at 14-18 weeks' gestation including 43 women that subsequently developed PE and 200 that were unaffected by PE. A Gaussian model was fitted to the log distribution of the multiple of the median (log MoM) PLAC1 mRNA in the PE group and in the unaffected group. Likelihood ratios for log MoM of circulating levels of mRNA for the PLAC1 gene were used to combine the a priori risk from maternal characteristics with MAP to produce patient-specific risks for each case. RESULTS: Screening by maternal characteristics (including BMI, woman's mother's history of PE, previous PE, and parity) (a priori risk) and MAP detected 46.8% of all cases of late PE at a fixed false-positive rate (FPR) of 10%. The addition of PLAC1 yielded a detection rate (DR) of 62.8% at the same level of FPR. PLAC1 alone yielded a DR of 30.2%. CONCLUSION: In late PE, molecular markers can be used to improve the DR of screening and can be a valid option for the biochemical approach. PMID- 25138313 TI - Super-responders to cardiac resynchronization therapy remain at risk for ventricular arrhythmias and benefit from defibrillator treatment. AB - AIMS: Mortality and ventricular arrhythmias are reduced in patients responding to cardiac resynchronization therapy (CRT). This response is accompanied by improvement in LVEF, and some patients even outgrow original eligibility criteria for implantable cardioverter-defibrillator (ICD) implantation. It is however unclear if these patients still benefit from ICD treatment. The current study aimed to evaluate if the incidence of ICD therapy is related to the extent of CRT response. METHODS AND RESULTS: All patients who underwent primary prevention CRT defibrillator implantation were included. They were divided into subgroups according to the reduction in LV end-systolic volume (LVESV) 6 months after implantation. Pre-defined subgroups were: negative responders (increased LVESV), non-responders (decreased LVESV 0-14%), responders (decreased LVESV 15-29%), and super-responders (decreased LVESV >=30%). During a median follow-up of 57 months (25th-75th percentile 39-84), 512 patients were studied [101 (20%) negative responders, 101 (20%) non-responders, 149 (29%) responders, and 161 (31%) super responders]. In the first year of follow-up super-responders received significantly less appropriate ICD therapy (3% vs. 12%; P < 0.001). The 5-year cumulative incidence of appropriate ICD therapy was 31% [95% confidence interval (CI) 19-43] in negative responders, 39% (95% CI 25-53) in non-responders, 34% (95% CI 25-43) in responders, and 27% (95% CI 18-35) in super-responders, respectively (p = 0.13). CONCLUSIONS: The extent of CRT response was associated with a parallel reduction of appropriate device therapy during the first year of follow-up. Thereafter, no association was observed. Furthermore, 23% of super responders were treated for potentially life-threatening arrhythmias and benefit from ICD treatment. PMID- 25138312 TI - Personal and psychosocial predictors of doping use in physical activity settings: a meta-analysis. AB - BACKGROUND: There is a growing body of empirical evidence on demographic and psychosocial predictors of doping intentions and behaviors utilizing a variety of variables and conceptual models. However, to date there has been no attempt to quantitatively synthesize the available evidence and identify the strongest predictors of doping. OBJECTIVES: Using meta-analysis, we aimed to (i) determine effect sizes of psychological (e.g. attitudes) and social-contextual factors (e.g. social norms), and demographic (e.g. sex and age) variables on doping intentions and use; (ii) examine variables that moderate such effect sizes; and (iii) test a path analysis model, using the meta-analyzed effect sizes, based on variables from the theory of planned behavior (TPB). DATA SOURCES: Articles were identified from online databases, by contacting experts in the field, and searching the World Anti-Doping Agency website. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Studies that measured doping behaviors and/or doping intentions, and at least one other demographic, psychological, or social-contextual variable were included. We identified 63 independent datasets. STUDY APPRAISAL AND SYNTHESIS METHOD: Study information was extracted by using predefined data fields and taking into account study quality indicators. A random effects meta-analysis was carried out, correcting for sampling and measurement error, and identifying moderator variables. Path analysis was conducted on a subset of studies that utilized the TPB. RESULTS: Use of legal supplements, perceived social norms, and positive attitudes towards doping were the strongest positive correlates of doping intentions and behaviors. In contrast, morality and self-efficacy to refrain from doping had the strongest negative association with doping intentions and behaviors. Furthermore, path analysis suggested that attitudes, perceived norms, and self-efficacy to refrain from doping predicted intentions to dope and, indirectly, doping behaviors. LIMITATIONS: Various meta-analyzed effect sizes were based on a small number of studies, which were correlational in nature. This is a limitation of the extant literature. CONCLUSIONS: This review identifies a number of important correlates of doping intention and behavior, many of which were measured via self-reports and were drawn from an extended TPB framework. Future research might benefit from embracing other conceptual models of doping behavior and adopting experimental methodologies that will test some of the identified correlates in an effort to develop targeted anti-doping policies and programs. PMID- 25138311 TI - A systematic review and meta-analysis of concussion in rugby union. AB - BACKGROUND: Rugby Union, a popular full-contact sport played throughout the world, has one of the highest rates of concussion of all full-contact sports. OBJECTIVE: The aim of the current review was to systematically evaluate the available evidence on concussion in Rugby Union and to conduct a meta-analysis of findings regarding the incidence of concussion. METHODS: Articles were retrieved via a number of online databases. The current review examined all articles published in English up to May 2014 pertaining to concussion in Rugby Union players. The key search terms included 'Rugby Union', 'rugby', 'union', and 'football', in combination with the injury terms 'athletic injuries', 'concussion', 'sports concussion', 'sports-related concussion', 'brain concussion', 'brain injury', 'brain injuries', 'mild traumatic brain injury', 'mTBI', 'traumatic brain injury', 'TBI', 'craniocerebral trauma', 'head injury', and 'brain damage'. RESULTS: The final search outcome following the eligibility screening process resulted in the inclusion of 96 articles for this review. The meta-analysis included a total of 37 studies. The results of the meta-analysis revealed an overall incidence of match-play concussion in men's rugby-15s of 4.73 per 1,000 player match hours. The incidence of concussion during training was 0.07 per 1,000 practice hours. The incidence of concussion in women's rugby-15s was 0.55 per 1,000 player match hours. In men's rugby-7s match-play, concussion incidence was 3.01 per 1,000 player match hours. The incidence of concussion varied considerably between levels of play, with elite level play recording a rate of 0.40 concussions per 1,000 player match hours, schoolboy level 0.62 concussions per 1,000 player match hours, and the community or sub-elite level recording a rate of 2.08 concussions per 1,000 player match hours. The incidence of concussion in men's rugby-15s as a function of playing position (forwards vs. backs) was 4.02 and 4.85 concussions per 1,000 player match hours, respectively. CONCLUSIONS: Concussion is a common injury sustained and reported in match play and to a lesser extent during practice by Rugby Union players. Based on the available published data, there appears to be a variation in risk of concussion across level of play, with the sub-elite level having the greatest incidence of injury. Future research focused on studying the acute consequences and best management strategies in current players, and the potential longer term outcomes of concussion in retired players, is needed. A focus on the areas of prevention, injury identification, and medical management, and risk for long-term outcomes will be of benefit to current athletes. PMID- 25138314 TI - Physiological and biochemical characterization of Azospirillum brasilense strains commonly used as plant growth-promoting rhizobacteria. AB - Azospirillum is a plant growth-promoting rhizobacteria (PGPR) genus vastly studied and utilized as agriculture inoculants. Isolation of new strains under different environmental conditions allows the access to the genetic diversity and improves the success of inoculation procedures. Historically, the isolation of this genus has been performed by the use of some traditional culture media. In this work we characterized the physiology and biochemistry of five different A. brasilense strains, commonly used as cereal inoculants. The aim of this work is to contribute to pose into revision some concepts concerning the most used protocols to isolate and characterize this bacterium. We characterized their growth in different traditional and non-traditional culture media, evaluated some PGPR mechanisms and characterized their profiles of fatty acid methyl esters and carbon-source utilization. This work shows, for the first time, differences in both profiles, and ACC deaminase activity of A. brasilense strains. Also, we show unexpected results obtained in some of the evaluated culture media. Results obtained here and an exhaustive knowledge revision revealed that it is not appropriate to conclude about bacterial species without analyzing several strains. Also, it is necessary to continue developing studies and laboratory techniques to improve the isolation and characterization protocols. PMID- 25138315 TI - Steric self-assembly of laterally confined organic semiconductor molecule analogues. AB - Self-assembly of planar molecules can be a critical route to control morphology in organic optoelectronic systems. In this study, Monte Carlo simulations were performed with polygonal disc analogues to planar semiconducting molecules under confinement. By examining statistically the molecular density and configurations of such analogues, we have observed that the symmetry of the confining medium can have a greater impact on the final densified particle configurations than the intramolecular interactions. Using the steric frustration imparted by confinement, novel self-assembled (partially) ordered phases are available. Our Monte Carlo simulations suggest new avenues to control ordering and morphology of planar molecules, which are critical for high-performance organic optoelectronic devices. PMID- 25138318 TI - "The beautyful ones are not yet born" might not hold true for much longer: Njideka Akunyili. PMID- 25138319 TI - CDC: Ebola risk to US patients is low, but clinicians should be on alert. PMID- 25138329 TI - A piece of my mind. Beyond conflicts of interest: disclosing medical biases. PMID- 25138330 TI - Bronchiolitis, deception in research, and clinical decision making. PMID- 25138331 TI - Newborn screening for severe combined immunodeficiency: progress and challenges. PMID- 25138332 TI - Effect of oximetry on hospitalization in bronchiolitis: a randomized clinical trial. AB - IMPORTANCE: Routine use of pulse oximetry has been associated with changes in bronchiolitis management and may have lowered the hospitalization threshold for patients with bronchiolitis. OBJECTIVE: To examine if infants with bronchiolitis whose displayed oximetry measurements have been artificially elevated 3 percentage points above true values experience hospitalization rates at least 15% lower compared with infants with true values displayed. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, parallel-group trial conducted from 2008 to 2013 in a tertiary-care pediatric emergency department in Toronto, Ontario, Canada. Participants were 213 otherwise healthy infants aged 4 weeks to 12 months with mild to moderate bronchiolitis and true oxygen saturations of 88% or higher. INTERVENTIONS: Pulse oximetry measurements with true saturation values displayed or with altered saturation values displayed that have been increased 3 percentage points above true values. MAIN OUTCOMES AND MEASURES: The primary outcome was hospitalization within 72 hours, defined as inpatient admission within this interval or active hospital care for greater than 6 hours. Secondary outcomes included the use of supplemental oxygen in the emergency department, level of physician agreement with discharge from the emergency department, length of emergency department stay, and unscheduled visits for bronchiolitis within 72 hours. RESULTS: Forty-four of 108 patients (41%) in the true oximetry group and 26 of 105 (25%) in the altered oximetry group were hospitalized within 72 hours (difference, 16% [95% CI for the difference, 3.6% to 28.4%]; P = .005). Using the emergency department physician as a random effect, the primary treatment effect remained significant (adjusted odds ratio, 4.0 [95% CI, 1.6 to 10.5]; P = .009). None of the secondary outcomes were significantly different between the groups. There were 23 of 108 (21.3%) subsequent unscheduled medical visits for bronchiolitis in the true oximetry group and 15 of 105 (14.3%) in the altered oximetry group (difference, 7% [95% CI, -0.3% to 0.2%]; P = .18). CONCLUSIONS AND RELEVANCE: Among infants presenting to an emergency department with mild to moderate bronchiolitis, those with an artificially elevated pulse oximetry reading were less likely to be hospitalized within 72 hours or to receive active hospital care for more than 6 hours than those with unaltered oximetry readings. This suggests that oxygen saturation should not be the only factor in the decision to admit, and its use may need to be reevaluated. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00673946. PMID- 25138333 TI - Sustained care intervention and postdischarge smoking cessation among hospitalized adults: a randomized clinical trial. AB - IMPORTANCE: Health care systems need effective models to manage chronic diseases like tobacco dependence across transitions in care. Hospitalizations provide opportunities for smokers to quit, but research suggests that hospital-delivered interventions are effective only if treatment continues after discharge. OBJECTIVE: To determine whether an intervention to sustain tobacco treatment after hospital discharge increases smoking cessation rates compared with standard care. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial compared sustained care (a postdischarge tobacco cessation intervention) with standard care among 397 hospitalized daily smokers (mean age, 53 years; 48% were males; 81% were non-Hispanic whites) who wanted to quit smoking after discharge and received a tobacco dependence intervention in the hospital; 92% of eligible patients and 44% of screened patients enrolled. The study was conducted from August 2010 through November 2012 at Massachusetts General Hospital. INTERVENTIONS: Sustained care participants received automated interactive voice response telephone calls and their choice of free smoking cessation medication (any type approved by the US Food and Drug Administration) for up to 90 days. The automated telephone calls promoted cessation, provided medication management, and triaged smokers for additional counseling. Standard care participants received recommendations for postdischarge pharmacotherapy and counseling. MAIN OUTCOMES AND MEASURES: The primary outcome was biochemically confirmed past 7-day tobacco abstinence at 6-month follow-up after discharge from the hospital; secondary outcomes included self-reported tobacco abstinence. RESULTS: Smokers randomly assigned to sustained care (n = 198) used more counseling and more pharmacotherapy at each follow-up assessment than those assigned to standard care (n = 199). Biochemically validated 7-day tobacco abstinence at 6 months was higher with sustained care (26%) than with standard care (15%) (relative risk [RR], 1.71 [95% CI, 1.14-2.56], P = .009; number needed to treat, 9.4 [95% CI, 5.4-35.5]). Using multiple imputation for missing outcomes, the RR for 7-day tobacco abstinence was 1.55 (95% CI, 1.03-2.21; P = .04). Sustained care also resulted in higher self-reported continuous abstinence rates for 6 months after discharge (27% vs 16% for standard care; RR, 1.70 [95% CI, 1.15-2.51]; P = .007). CONCLUSIONS AND RELEVANCE: Among hospitalized adult smokers who wanted to quit smoking, a postdischarge intervention providing automated telephone calls and free medication resulted in higher rates of smoking cessation at 6 months compared with a standard recommendation to use counseling and medication after discharge. These findings, if replicated, suggest an approach to help achieve sustained smoking cessation after a hospital stay. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01177176. PMID- 25138335 TI - Red papules on the tongue of a patient with hemiparesis. PMID- 25138336 TI - Elevated serum ferritin. PMID- 25138337 TI - Seroprevalence of herpes simplex virus type 1 and 2 among pregnant women, 1989 2010. PMID- 25138338 TI - Tadalafil for erectile dysfunction prevention after radiotherapy for prostate cancer. PMID- 25138339 TI - Tadalafil for erectile dysfunction prevention after radiotherapy for prostate cancer--reply. PMID- 25138334 TI - Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. AB - IMPORTANCE: Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births. OBJECTIVES: To present data from a spectrum of SCID newborn screening programs, establish population based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN: Epidemiological and retrospective observational study. SETTING: Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES: Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS: Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE: Newborn screening in 11 programs in the United States identified SCID in 1 in 58,000 infants, with high survival. The usefulness of detection of non SCID T-cell lymphopenias by the same screening remains to be determined. PMID- 25138340 TI - Statins and ischemic stroke. PMID- 25138341 TI - Treatment for opioid use disorder. PMID- 25138342 TI - Statins and ischemic stroke--reply. PMID- 25138344 TI - Treatment for opioid use disorder--reply. PMID- 25138346 TI - Hasty generalizations. PMID- 25138347 TI - The effect of passively acquired antibodies on Lawsonia intracellularis infection and immunity in the horse. AB - REASONS FOR PERFORMING STUDY: Multiple hypotheses into the age-based susceptibility of animals to Lawsonia intracellularis exist, including the decline of passively acquired antibodies. OBJECTIVES: To determine whether the decline in passively acquired antibodies in horses is responsible for the age predilection of equine proliferative enteropathy (EPE). Additional objectives included examination of various risk factors for the development of EPE as well as the determination of naturally occurring attack rates for clinical and subclinical EPE. STUDY DESIGN: Prospective, multifarm field study. METHODS: A total of 369 mare and foal pairs from 15 central Kentucky Thoroughbred farms were used in this study, which took place from January 2012 to February 2013. Serum samples were collected from mares and foals within 48 h of parturition, and then monthly from foals to February of their yearling year. Lawsonia intracellularis specific antibodies were measured using an enzyme-linked immunosorbent assay. RESULTS: No effect of passively acquired antibodies on the occurrence of presumptive clinical or subclinical EPE was noted. In total, 5.3% and 6.3% of seropositive horses developed presumptive clinical or subclinical EPE, respectively. In multiple logistic regression models, colts were at a significantly greater risk than fillies of developing presumptive clinical EPE (odds ratio [OR] 5.468, 95% confidence interval [CI] 1.134-26.362, P = 0.034) or a combination of either presumptive clinical or subclinical EPE (OR 3.861, 95% CI 1.461-10.206, P = 0.006) while foals that were weaned in September or beyond were at a lower risk of developing presumptive EPE (OR = 0.281, 95% CI 0.0807-0.981, P = 0.05). CONCLUSIONS: This is the first study to show that passively acquired antibodies to L. intracellularis do not have an effect on the occurrence of clinical or subclinical EPE. A number of novel findings, including identification of the disease rate among naturally exposed horses, warrant additional work as they may help to identify potential risk factors for L. intracellularis exposure and/or the reservoir host(s) of the bacterium. PMID- 25138348 TI - Controlled release of ziprasidone solid dispersion systems from osmotic pump tablets with enhanced bioavailability in the fasted state. AB - OBJECTIVE: The purpose of this work was to develop a controlled release of ziprasidone with no food effect by the osmotic release strategy. METHODS: The solution of ziprasidone and poloxamer188 (P188) with different weight ratios was spray-dried to form solid dispersion of ziprasidone (SD-ZIP). The SD-ZIP was characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (X-RD) and solubility testing. The SD ZIP osmotic pump tablets were prepared by wet granulation method. The effect of formulation variables on the release characteristic was investigated. The SD-ZIP osmotic pump tablets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation Zeldox(r) as a control. RESULTS: The results of DSC and X-RD indicated that ziprasidone resides in P188 with no crystalline changes. Solubility studies demonstrated that the solubility of SD-ZIP was substantially improved compared to ziprasidone and physical mixtures of ziprasidone and P188. The optimized formulation and drug release profiles of SD-ZIP osmotic pump tablets in different medium were obtained which showed typical osmotically controlled release and could fitted to zero-order kinetics with good linear correlation. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolong actions and no food effect was achieved simultaneously in SD-ZIP osmotic pump tablet compared with Zeldox(r). CONCLUSION: The SD-ZIP osmotic pump tablet could be able to enhance the bioavailability in the fasted state and showed sustained release with prolonged actions. PMID- 25138349 TI - Preparation and evaluation of SEDDS of simvastatin by in vivo, in vitro and ex vivo technique. AB - The objective of this work was to formulate a Self Emulsifying Drug Delivery System (SEDDS) of simvastatin, a poorly soluble drug and to evaluate by in vivo, in vitro and ex vivo techniques. Oils and surfactants were screened out depending upon their solubilizing capacity. Among all of the solvents, Capryol 90 showed good solubilizing capacity. It dissolved 105 mg/ml of simvastatin. Tween-80 also showed good solubilizing capacity which was 117 mg/ml. The two excipients were used to prepare simvastatin SEDDS. Formulations were initially checked for the color, clarity and sedimentation. The SEDDS formulations were transparent and clear. Formulation F2 containing 7:3 (m/m) mixture of Capryol 90/Tween-80 produced smallest micro-emulsion with particles size of 0.074 um and drug release was higher than other formulation (102% within 20 min). Ex vivo study of the SEDDS formulation was evaluated using guinea pig intestinal sac. Drug diffused from F2 formulation was significantly higher than pure drug (p < 0.001). In vivo study of SEDDS was performed in albino mice using plasma cholesterol level as a pharmacodynamic marker parameter. The test formulation (F2) appeared remarkable reduction in plasma cholesterol level, after oral administration which showed that SEDDS may be an effective technique for the oral administration of simvastatin. PMID- 25138350 TI - Analysis of curing of a sustained release coating formulation by application of NIR spectroscopy to monitor changes associated with glyceryl monostearate. AB - For controlled release, latex or pseudolatex coatings to function as designed, it must be cured at temperatures at or slightly above the polymer's glass transition temperature. The focus of this study is to develop an understanding of the curing process and to develop near infrared spectroscopy as a tool for monitoring curing. Differential scanning calorimetry studies were used to determine how the thermal properties of glyceryl monostearate (GMS) and its polymorphic forms relate to the extent of Eudragit(r) polymer coat curing at different curing temperatures. The different GMS melting endotherms were used to monitor the extent of curing and as references for model development. The calculated melting peak areas for the GMS were plotted versus time and found to be dependent on time and temperature used for curing. Principal component analysis and parallel factor analysis were used to investigate the effect of curing on the films and showed that spectral changes could be could be directly related to the changes associated with the GMS during curing. Partial least square models developed could predict the extent of curing and the final state of GMS post curing. PMID- 25138353 TI - Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy. AB - ETHNOPHARMACOLOGICAL RELEVANCE: A substantial proportion of the population in Papua New Guinea (PNG) lives with human immunodeficiency virus (HIV). Treatment requires lifelong use of antiretroviral therapy (ART). The majority of people in PNG use traditional medicines (TM) derived from plants for all types of health promotions. Consequently, there is a concern that herb-drug interactions may impact the efficacy of ART. Herb-drug, or drug-drug, interactions occur at the level of metabolism through two major mechanisms: enzyme induction or enzyme inhibition. In this study, extracts of commonly-used medicinal plants from PNG were screened for herb-drug interactions related to cytochrome P450s (CYPs). MATERIALS AND METHODS: Sixty nine methanol extracts of TM plants were screened for their ability to induce CYPs by human aryl hydrocarbon receptor- (hAhR-) and human pregnane X receptor- (hPXR-) dependent mechanisms, utilizing a commercially available cell-based luciferase reporter system. Inhibition of three major CYPs, CYP1A2, CYP3A4, and CYP2D6, was determined using human liver microsomes and enzyme-selective model substrates. RESULTS: Almost one third of the TM plant extracts induced the hAhR-dependent expression of CYP1A2, the hPXR-dependent expression of CYP3A4, or both. Almost two thirds inhibited CYP1A2, CYP3A4, or CYP2D6, or combinations thereof. Many plant extracts exhibited both induction and inhibition properties. CONCLUSIONS: We demonstrated that the potent and selective ability of extracts from PNG medicinal plants to affect drug metabolizing enzymes through induction and/or inhibition is a common phenomenon. Use of traditional medicines concomitantly with ART could dramatically alter the concentrations of antiretroviral drugs in the body; and their efficacy. PNG healthcare providers should counsel HIV patients because of this consequence. PMID- 25138354 TI - Inhibition of the toxic effects of Bothrops asper venom by pinostrobin, a flavanone isolated from Renealmia alpinia (Rottb.) MAAS. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Renealmia alpinia has been traditionally used to treat snakebites by indigenous Embera-Katios tribes belonging to the regions of Antioquia and Choco, Colombia, and it has been shown to inhibit the enzymatic and biological activities of Bothrops venoms and their purified phospholipase A2 (PLA2) toxins. In addition to its common local usage against snakebites, Renealmia alpinia is commonly used to treat pain. To evaluate the inhibitory ability of pinostrobin, the main compound in the dichloromethane extract of Renealmia alpinia, on the toxic effects of Bothrops asper venom through in vitro and in vivo models and to evaluate its activity against pain and edema. MATERIALS AND METHODS: Pinostrobin was isolated from the dichloromethane extract of Renealmia alpinia leaves. The protective properties of the extract and of pinostrobin against the indirect hemolytic, coagulant and proteolytic effects of Bothrops asper venom were evaluated in vitro, and the anti-hemorrhagic and anti inflammatory activity were evaluated in vivo. RESULTS: Renealmia alpinia extract significantly inhibited the proteolytic activity and indirect hemolytic activity of Bothrops asper venom at a venom:extract ratio of 1:20. Moreover, the present data demonstrate that pinostrobin may mitigate some venom-induced local tissue damage due to hemorrhagic effects, and the compound is also responsible for the analgesic and anti-inflammatory activity of the extract from Renealmia alpinia. This is the first report to describe pinostrobin in the species Renealmia alpinia and its properties in vitro against Bothrops asper venom. CONCLUSION: Our studies of the activity of Renealmia alpinia against the venom of Bothrops asper have confirmed that this species possesses inhibitory effects against Bothrops asper venom in both in vitro and in vivo models and that these effects may be due to pinostrobin, supporting the traditional usage of the plant. Additionally, pinostrobin may be responsible for the anti-hemorrhagic and analgesic activity (peripheral analgesic activity) of Renealmia alpinia. PMID- 25138355 TI - Itching in patients with chronic hand eczema: data from the CARPE registry. AB - BACKGROUND: Itching is a leading symptom of chronic hand eczema (CHE) having a great impact on patients. The determinants of itching in CHE are unclear. OBJECTIVE: We performed a cross-sectional analysis investigating factors associated with the presence and severity of itch in CHE patients from the CARPE registry. METHODS: We present baseline data on itch in relationship with sociodemographic factors, severity of CHE, atopy, contact allergy, treatment and patient- reported outcomes including health-related quality of life (HRQoL). RESULTS: Of 1,051 patients with CHE, 78.1% reported itching. Significant positive associations with itching were observed for younger age groups (17-25 and 26-45 years), for moderate, severe and very severe CHE and for small/moderate impairment in HRQoL. Atopic skin diathesis, hardly being able to realize treatment recommendations and very or extremely large impairments in HRQoL were associated with itch severity. CONCLUSION: Taking the identified variables into account may help identify vulnerable groups most affected by (severe) itch. PMID- 25138356 TI - FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination. AB - BACKGROUND: FTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease. METHODS: Mice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice. RESULTS: Administration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-gamma, TNF-alpha or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation. CONCLUSION: These findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model. PMID- 25138357 TI - Yeast studies reveal moonlighting functions of the ancient actin cytoskeleton. AB - Classic functions of the actin cytoskeleton include control of cell size and shape and the internal organization of cells. These functions are manifest in cellular processes of fundamental importance throughout biology such as the generation of cell polarity, cell migration, cell adhesion, and cell division. However, studies in the unicellular model eukaryote Saccharomyces cerevisiae (Baker's yeast) are giving insights into other functions in which the actin cytoskeleton plays a critical role. These include endocytosis, control of protein translation, and determination of protein 3-dimensional shape (especially conversion of normal cellular proteins into prions). Here, we present a concise overview of these new "moonlighting" roles for the actin cytoskeleton and how some of these roles might lie at the heart of important molecular switches. This is an exciting time for researchers interested in the actin cytoskeleton. We show here how studies of actin are leading us into many new and exciting realms at the interface of genetics, biochemistry, and cell biology. While many of the pioneering studies have been conducted using yeast, the conservation of the actin cytoskeleton and its component proteins throughout eukaryotes suggests that these new roles for the actin cytoskeleton may not be restricted to yeast cells but rather may reflect new roles for the actin cytoskeleton of all eukaryotes. PMID- 25138358 TI - How to choose an anesthesia ventilator? AB - During the past few years, many manufacturers have developed a new generation anesthesia ventilators or anesthesia workstations with innovative technology and introduced so-called new ventilatory modes in the operating room. The aim of this article is to briefly explain how an anesthesia ventilator works, to describe the main differences between the technologies used, to describe the main criteria for evaluating technical and pneumatic performances and to list key elements not to be forgotten during the process of acquiring an anesthesia ventilator. PMID- 25138359 TI - Large Urethro-Vesico-Vaginal Fistula due to a Vaginal Foreign Body in a 22-Year Old Woman: Case Report and Literature Review. AB - In the non-industrialized countries of Africa and Asia obstetric fistulas are more frequently caused by prolonged labour, whereas in countries with developed healthcare systems they are generally the result of complications of gynaecological surgery or, rarely, benign pathologies like inflammation or foreign bodies. A 22-year-old woman was brought to the gynaecology clinic because of foul-smelling vaginal discharge. On pelvic examination a ring-like foreign body was impacted between the anterior and posterior vaginal wall. MRI scan confirmed the presence of a cylindrical foreign body in the vagina and the patient revealed that she had 'involuntarily' inserted a plastic bubble bath cap into the vagina. At surgery removal of the cap was difficult and at the end of the manoeuver evidence of a huge urethro-vesico-vaginal fistula occurred. The patient was discharged with bilateral ureteral stents and suprapubic catheter. After 3 months we performed an end-to-end anastomotic urethroplasty to repair the urethral avulsion and restored the bladder/trigonal and vaginal/cervical defects with 3 layers of sutures; 3 months later the patient had no complaints. Complex genital fistulas represent an extremely debilitating morbidity. In our case, a vaginal approach was successful, but the choice between an abdominal or vaginal approach depends on the surgeon's experience and training. PMID- 25138360 TI - Editorial. PMID- 25138361 TI - Biomechanics of incisor retraction with mini-implant anchorage. AB - Mini-implants have been successfully incorporated into orthodontic practice all over the world. One of the most popular applications of mini-implant anchorage is to facilitate retraction of the anterior teeth. This article reviews the mechanics involved in anterior tooth retraction with mini-implant supported anchorage. An attempt has been made to synthesize information available in the literature and present it in a manner that is easily understandable from a clinical perspective. We discuss the fundamental differences mini-implant based incisor retraction has when compared to conventional techniques, mechanical factors affecting this process and provide a step-by-step analysis of incisor retraction. In addition, various models of space closure are discussed that have evolved through careful evaluation of in vitro and in vivo experiments. PMID- 25138362 TI - An active, skeletally anchored transpalatal appliance for derotation, distalization and vertical control of maxillary first molars. AB - OBJECTIVE: The objective of this investigation was to evaluate treatment outcomes of the skeletally anchored 'Frog' appliance. DESIGN: A single-centre, retrospective study was performed. SETTING: Private orthodontic practice. PARTICIPANTS: Patients who had undergone comprehensive orthodontic treatment with the skeletally anchored 'Frog' appliance. METHODS: 43 participants (20 males and 23 females) who had received treatment with the skeletally anchored 'Frog' appliance where included. In order to explore dentoalveolar and skeletal treatment outcomes, pre- (T1) and post- (T2) treatment measurements were performed on patients' plaster models and cephalometric images. Comparisons between T1 and T2 were made by means of a Student's t-test. All statistical analyses were conducted at the 0.05 level of statistical significance. RESULTS: Study model analysis revealed a statistically significant derotation of maxillary molars (MUDeltaT2-T1=9.5 degrees , P<0.001) as well as an increase in transverse arch dimensions at the end of treatment (MUDeltaT2-T1=2.2 mm, P<0.001). Cephalometric changes included bodily distalization of maxillary molars (MUDelta(T2-T1)=-1.9 mm, P<0.001), as well as noticeable angular displacement (MUDeltaT2-T1=4.1 degrees , P=0.004). No significant anchorage loss was observed, as displayed by the limited change in maxillary incisor position (MUDelta(T1 T2)=0.2 mm, P=0.45). In addition, excellent vertical control of the maxillary molars was achieved, with no change in the mandibular plane (ML/NSL) angle (MUDeltaT2-T1=0.3 degrees , P=0.38). CONCLUSIONS: The skeletal 'Frog' is effective in derotating and distalizing maxillary molars without anchorage loss and with excellent vertical control. PMID- 25138363 TI - Hard and soft tissue considerations at mini-implant insertion sites. AB - Various factors influence where orthodontic mini-implants will be placed. This article highlights the pertinent variables that should find consideration when planning the placement of orthodontic mini-implants. PMID- 25138364 TI - Clinical outcomes of cases with missing lateral incisors treated with the 'T' Mesialslider. AB - The objective of this article is to review the fabrication and activation procedures of the 'T'-Mesialslider and to present the clinical outcomes in cases where canine substitution is the treatment of choice for missing maxillary lateral incisors. The 'T'-Mesialslider allows for effective mesial translation of the canines and the posterior dentition, without significant loss of anterior anchorage and with good vertical control. Possible adverse effects of the appliance and clinical recommendations for their management are also discussed. In canine substitution cases with high anchorage demands, the 'T'-Mesialslider provides an effective treatment option. PMID- 25138365 TI - Molar intrusion in the management of anterior openbite and 'high angle' Class II malocclusions. AB - Orthodontic correction of anterior openbite has conventionally involved extraction therapy or an adjunctive maxillary impaction osteotomy. However, bone anchored molar intrusion treatments have been reported in recent years as a less invasive alternative for such patients. This paper describes the concepts and treatment processes involved with mini-implant molar intrusion to correct anterior openbite and reduce patients' excessive vertical facial proportions. PMID- 25138366 TI - The Hybrid Hyrax Distalizer, a new all-in-one appliance for rapid palatal expansion, early class III treatment and upper molar distalization. AB - Growing class III patients with maxillary deficiency may be treated with a maxillary protraction facemask. Because the force generated by this appliance is applied to the teeth, the inevitable mesial migration of the dentition can result in anterior crowding, incisor proclination and a possible need for subsequent extraction therapy. The Hybrid Hyrax appliance, anchored on mini-implants in the anterior palate, can be used to overcome these side-effects during the facemask therapy. In some class III cases, there is also a need for subsequent distalization after the orthopaedic treatment. In this paper, clinical application of the Hybrid Hyrax Distalizer is described, facilitating both orthopaedic advancement of the maxilla and simultaneous orthodontic distalization of the maxillary molars. PMID- 25138367 TI - Mini-implant applications in orthognathic surgical treatment. AB - Orthognathic surgical treatment conventionally relies on the use of full arch fixed orthodontic appliances. However, the introduction of orthodontic mini implants has altered surgical options in terms of providing an alternative to fixation (intermaxillary fixation, IMF) screws and even to maxillary osteotomy. This paper describes the integration of mini-implants within orthognathic treatments in terms of 'surgery first' treatments and by introducing the concept of the conversion of bimaxillary cases into mandible-only surgery treatments. PMID- 25138368 TI - Temporary replacement of missing maxillary lateral incisors with orthodontic miniscrew implants in growing patients: rationale, clinical technique, and long term results. AB - The missing maxillary lateral incisor in adolescent patients presents an orthodontic challenge. Historically, there have been three treatment options to address this clinical problem: (1) canine substitution, (2) tooth auto transplantation, and (3) dental restoration. Unfortunately, these methods are not without limitation. A novel treatment concept, originating in 2003 and utilizing orthodontic miniscrew implants, is presented along with the rationale, clinical technique and 8 years of follow-up. PMID- 25138369 TI - Translational mini-screw implant research. AB - It is important to thoroughly test new materials as well as techniques when these innovations are to be utilized in the human clinical situation. Translational research fills this important niche. The purpose of translational research is to establish the continuity of evidence from the laboratory to the clinic and in so doing, provide evidence that the material is functioning appropriately and that the process in the human will be successful. This concept applies to the mini screw implant; which, has been very successfully introduced into the orthodontic armamentarium over the last decade for application as a temporary anchorage device. The examples of translational research that will be illustrated in this paper have paved the way to ensure that clinicians have evidence to confidently utilize mini-screw implants in orthodontic practice. Needless to say, more studies are needed to ensure a safe, effective and efficient manner to practice orthodontics. PMID- 25138371 TI - Resveratrol treatment as an adjunct to pharmacological management in type 2 diabetes mellitus--systematic review and meta-analysis. AB - The red wine polyphenol, resveratrol, is highly effective in treating type 2 diabetes mellitus (T2DM) in animal models, but there is no consensus regarding its efficacy in humans. We conducted a systematic review, which included searches in nine scholarly databases and six clinical trial registries, and identified randomized controlled clinical trials whereby resveratrol was used as an adjunct to pharmaceutical interventions in T2DM. Meta-analysis on clinical parameters was performed for available data. Of 764 articles originally identified, data from six unique datasets, examining a total of 196 T2DM patients (104 resveratrol, 92 control/placebo) ultimately met inclusion criteria. Statistically significant (p < 0.05) positive effects, indicating that resveratrol supplementation was more effective than placebo/control, were identified for systolic blood pressure, hemoglobin A1c, and creatinine, but not for fasting glucose, homeostatic model assessment of insulin resistance, diastolic blood pressure, insulin, triglycerides, LDL, or HDL cholesterol. No major adverse events were reported and side effects of resveratrol were not different than placebo/control. Though limitations in sample size and treatment duration preclude definitive changes in clinical practice, significant improvements in multiple cardiometabolic biomarkers and an excellent safety profile support resveratrol as a leading candidate as an adjunct to pharmacological management of T2DM. PMID- 25138370 TI - Non-HLA genes PTPN22, CDK6 and PADI4 are associated with specific autoantibodies in HLA-defined subgroups of rheumatoid arthritis. AB - INTRODUCTION: Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serves as a helpful discriminator in genetic studies and today anti citrullinated cyclic peptide (anti-CCP) antibody positivity is employed for diagnosis of disease. The HLA-DRB1 locus is known as the most important genetic contributor for the risk of RA, but is not sufficient to drive autoimmunity and additional genetic and environmental factors are involved. Hence, we addressed the association of previously discovered RA loci with disease-specific autoantibody responses in RA patients stratified by HLA-DRB1*04. METHODS: We investigated 2178 patients from three RA cohorts from Sweden and Spain for 41 genetic variants and four autoantibodies, including the generic anti-CCP as well as specific responses towards citrullinated peptides from vimentin, alpha-enolase and type II collagen. RESULTS: Our data demonstrated different genetic associations of autoantibody-positive disease subgroups in relation to the presence of DRB1*04. Two specific subgroups of autoantibody-positive RA were identified. The SNP in PTPN22 was associated with presence of anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Cochran-Mantel-Haenszel test P = 0.0001, P corrected <0.05), whereas SNPs in CDK6 and PADI4 were associated with anti-CCP status in DRB1*04 negative patients (Cochran-Mantel Haenszel test P = 0.0004, P corrected <0.05 for both markers). Additionally we see allelic correlation with autoantibody titers for PTPN22 SNP rs2476601 and anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02) and between CDK6 SNP rs42041 and anti-CCP in non-carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02). CONCLUSION: These data point to alternative pathways for disease development in clinically similar RA subgroups and suggest an approach for study of genetic complexity of disease with strong contribution of HLA. PMID- 25138372 TI - Human mate selection and addiction: a conceptual critique. AB - The authors review past work on modeling human mate selection, and suggest, using illustrations from existing literature on the impact of alcoholism on relationship formation and dissolution and reproduction, that the challenges of adequately characterizing human mate selection have not yet been overcome. Some paths forwards are suggested. PMID- 25138373 TI - Early erythropoietin in post-diarrheal hemolytic uremic syndrome: a case-control study. AB - BACKGROUND: Although erythropoietin (EPO) deficiency has been reported in children with post-diarrheal hemolytic uremic syndrome (D + HUS), very limited clinical data on EPO use in this disease are currently available. In this case control study we examined whether EPO administration would reduce the number of red blood cell (RBC) transfusions in D + HUS patients under our care. METHODS: Data from children treated exclusively with RBC transfusions (controls; n = 21) were retrospectively compared with data on those who also received EPO for the treatment of anemia (cases; n = 21). RESULTS: Both patient groups were similar in age (p = 0.9), gender (p = 0.12), weight (p = 1.00) and height (p = 0.66). Acute phase severity was also comparable, as inferred by the need for dialysis (p = 0.74), the duration of dialysis (p = 0.3), length of hospitalization (p = 0.81), presence of severe bowel (p = 1.00) or neurological injury (p = 0.69), arterial hypertension (p = 1.00) and death (p = 1.00). No differences in the hemoglobin level at admission (p = 0.51) and discharge (p = 0.28) were noted. Three children treated with EPO and two controls did not require any RBC transfusion (p = 1.00). Median number of RBC transfusions needed by cases and controls was 2 (p = 0.52). CONCLUSION: Treatment with EPO did not reduce the number of RBC transfusions in D + HUS children. Assessment of EPO efficacy in D + HUS merits further studies. PMID- 25138374 TI - Mechanism of the palladium-catalyzed hydrothiolation of alkynes to thioethers: a DFT study. AB - The mechanisms of the palladium-catalyzed hydrothiolation of alkynes with thiols were investigated using density functional theory at the B3LYP/6-31G(d, p) (SDD for Pd) level. Solvent effects on these reactions were explored using the polarizable continuum model (PCM) for the solvent tetrahydrofuran (THF). Markovnikov-type vinyl sulfides or cis-configured anti-Markovnikov-type products were formed by three possible pathways. Our calculation results suggested the following: (1) the first step of the cycle is a proton-transfer process from thiols onto the palladium atom to form a palladium-thiolate intermediate. The palladium-thiolate species is attacked on alkynes to obtain an elimination product, liberating the catalyst. (2) The higher activation energies for the alkyne into the palladium-thiolate bond indicate that this step is the rate determining step. The Markovnikov-type vinyl sulfide product is favored. However, for the aromatic alkyne, the cis-configured anti-Markovnikov-type product is favored. (3) The activation energy would reduce when thiols are substituted with an aromatic group. Our calculated results are consistent with the experimental observations of Frech and colleagues for the palladium-catalyzed hydrothiolation of alkynes to thiols. PMID- 25138375 TI - DFT study of the per-6-amino-beta-cyclodextrin as catalyst in synthesis of 2-aryl 2,3-dihydro-4-quinolones. AB - The synthesis of 2-aryl-2,3-dihydro-4-quinolones in the presence of per-6-amino beta-cyclodextrin (per-6-ABCD) as catalyst can improve selectivity and yield. The interaction between per-6-ABCD and benzaldehyde or o-aminoacetophenone plays an important role in this reaction. This paper studies the complexes of per-6-ABCD with benzaldehyde and o-aminoacetophenone using density functional theory (DFT) method. The reaction process is investigated by studying the energy of the reactants and the product. Hydrogen bonds are researched on the basis of natural bonding orbital (NBO) analysis, the results propose the donor-acceptor interactions of complex. The Mulliken charge and frontier orbital are employed for revealing the charge distribution. In addition, (13)C nuclear magnetic resonance ((13)CNMR) spectroscopy shows that the carbon atom on the aldehyde group for benzaldehyde, carbonyl group and the carbon atom connected with carbonyl group for o-aminoacetophenone are apparently activated in the cavity of per-6-ABCD. The probable catalytic mechanism of per-6-ABCD is discussed in terms of the calculated parameters. PMID- 25138376 TI - Measurement of neck circumference and its correlation with body composition in a sample of students in Sao Paulo, Brazil. AB - PURPOSE: The purpose of this study was to verify the correlation between neck circumference (NC) and body mass index (BMI) in children, and to determine NC percentiles for Brazilian children. METHODS: The subjects of this cross-sectional study were students between the ages of 6 and 19 years from five schools in Sao Paulo, Brazil. Clinical and anthropometric data were collected from the students from April 2011 to June 2012. NC was measured at the level of the cricoid cartilage. We calculated Pearson correlation coefficients between NC and other indices of obesity with Sigma Stat 3.5. NC percentiles were produced using the LMS (lambda, mu, and sigma) method (STATA 12.0). RESULTS: Among 2,794 students, 49.9% were male. NC was significantly correlated with age, BMI, waist circumference (WC), and body fat percentage (%BF). The NC of boys was greater than that of girls. The NC curves of smoothed 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles were constructed by age and sex. CONCLUSIONS: NC can be used in the assessment of obesity in childhood. There was a positive correlation between NC and BMI, WC and %BF. This study was the first to provide NC percentiles for children in Brazil. PMID- 25138377 TI - The effectiveness of community-based loan funds for transport during obstetric emergencies in developing countries: a systematic review. AB - OBJECTIVE: Scarcity and costs of transport have been implicated as key barriers to accessing care when obstetric emergencies occur in community settings. Community-based loans have been used to increase utilization of health facilities and potentially reduce maternal mortality by providing funding at community level to provide emergency transport. This review aimed to provide evidence of the effect of community-based loan funds on utilization of health facilities and reduction of maternal mortality in developing countries. METHODS: Electronic databases of published literature and websites were searched for relevant literature using a pre-defined set of search terms, inclusion and exclusion criteria. Screening of titles, abstracts and full-text articles were done by at least two reviewers independently. Quality assessment was carried out on the selected papers. Data related to deliveries and obstetric complications attended at facilities, maternal deaths and live births were extracted to measure and compare the effects of community-based loan funds using odds ratios (ORs) and reductions in maternal mortality ratio. Forest plots are presented where possible. RESULTS: The results of the review show that groups where community based loan funds were implemented (alongside other interventions) generally recorded increases in utilization of health facilities for deliveries, with ORs of 3.5 (0.97-15.48) and 3.55 (1.56-8.05); and an increase in utilization of emergency obstetric care with ORs of 2.22 (0.51-10.38) and 3.37 (1.78-6.37). Intervention groups also experienced a positive effect on met need for complications and a reduction in maternal mortality. CONCLUSION: There is some evidence to suggest that community-based loan funds as part of a multifaceted intervention have positive effects. Conclusions are limited by challenges of study design and bias. Further studies which strengthen the evidence of the effects of loan funds, and mechanism for their functionality, are recommended. PMID- 25138380 TI - Abstracts of the American Academy for Cerebral Palsy and Developmental Medicine 68th Annual Meeting, 10-13 September, 2014, San Diego, California, USA. PMID- 25138378 TI - Ganoderic acid Me induces the apoptosis of competent T cells and increases the proportion of Treg cells through enhancing the expression and activation of indoleamine 2,3-dioxygenase in mouse lewis lung cancer cells. AB - The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. It is known that ganoderic acid Me can enhance IFN-gamma expression and IDO is preferentially induced by IFN-gamma. However, whether GA-Me can induce IDO expression has not been clarified yet. We established stable clones of IDO-overexpressing 2 LL cells (2LL-EGFP-IDO). After co-culturing with IDO expressing or control vector-transfected 2LL-EGFP cells, T cell apoptosis was determined and the proportion of the regulatory T cells (Tregs) and CD8+ T cell subset was measured. The total cellular protein samples of 2 LL-EGFP-IDO cells were isolated for detecting JAK-STAT1 signalling pathway. Co-culture supernatants were used to detect amino acids and cytokines. IDO transfected 2 LL cells yielded high level of IDO enzymatic activity, resulting in complete depletion of tryptophan from the culture medium. We found that apoptosis occurred in T cells after cocultured with IDO+2LL cells and the proportion of CD4+CD25+ cells and FoxP3+ cells increased while CD8+ cells decreased. The specific inhibitor of IDO, 1-D-MT and GA-Me efficiently enhanced T cell apoptosis, increased Tregs, and reduced CD8+ T cells in vitro. Increased expression of IDO, p-JAK1 and p-STAT1 were confirmed by Western blot analysis. The levels of IFN-gamma, IL-10, LDH and kynurenine in co-culture supernatant correspondingly increased, while tryptophan reduced. These results suggest that GA-Me contributing to IDO helps to create a tolerogenic milieu in lung tumors by directly inducing T cell apoptosis, restraining CD8+ T cell activation, and enhancing Treg-mediated immunosuppression. PMID- 25138381 TI - West Nile virus: should pediatricians care? AB - Given the recurrent serious outbreaks of West Nile Virus (WNV) in the United States over the past decade, the spread to Canada and South America, the recurrent outbreaks in Europe, and the potential for serious neurological disease even in children under 18 years, paediatricians in affected areas must consider WNV in the differential diagnosis of all children presenting with aseptic meningitis, encephalitis and acute flaccid paralysis. Additionally, given that WNV encephalitis can occur after WNV infection, suspicion for neurological WNV disease must remain high even after otherwise benign febrile illnesses if the child lives in or has traveled to an affected region. Under-diagnosis in the pediatric population is likely a serious problem, necessitating further educational efforts. More follow-up studies of WNV neurological disease in children and youth are needed to better understand the potential long-term sequelae during vulnerable times of neurodevelopment and neural remodeling. Similarly, more research is need on short and long-term fetal outcomes of maternal WNV infection. PMID- 25138382 TI - The association of major patterns of physical activity, sedentary behavior and sleep with health-related quality of life: a cohort study. AB - OBJECTIVE: To examine the prospective association of patterns of physical activity, sedentary behavior and sleep with health-related quality of life (HRQL) in the general population of Spain. METHODS: A cohort study with 4271 individuals aged >= 18 years was recruited in 2008-2010 and followed-up prospectively through 2012. Activity patterns were derived from factor analysis. HRQL was assessed with the SF-12 questionnaire, and suboptimal HRQL was defined as a score below the sex specific sample median. RESULTS: Three main activity patterns were identified. A higher adherence to the pattern named "vigorous activity-seated at the computer" was inversely associated with a suboptimal score in the physical-composite summary (PCS) of the SF-12 (multivariate adjusted odds ratio [aOR] for the highest vs. the lowest quartile 0.71; 95% confidence interval [IC] 0.55-0.90; p trend=0.003). The "light activity-seated for reading" pattern was inversely associated with a suboptimal score in the mental-composite summary (aOR=0.73; 95% CI=0.61-0.89; p-trend=0.002). However, a higher adherence to the "seated for watching TV-daytime sleeping" pattern was directly associated with suboptimal PCS (aOR=1.35; 95% CI=1.10-1.66; p-trend=0.008). CONCLUSION: Patterns including any physical activity were associated with better physical or mental HRQL. However, a pattern defined by sedentary behavior with diurnal sleep showed worse HRQL and should be a priority target of preventive interventions. PMID- 25138384 TI - Hematologic findings predictive of bone marrow disease in dogs with multicentric large-cell lymphoma. AB - BACKGROUND: Evaluation of the bone marrow is needed for complete staging in dogs with multicentric large-cell lymphoma, but is often omitted in clinical practice. OBJECTIVES: The objective was to determine if routine peripheral blood findings, including microscopic evaluation of blood smears, can predict the presence of bone marrow involvement in dogs with lymphoma. METHODS: Hematologic data including evaluation of blood smears and bone marrow aspirates from 107 dogs newly diagnosed with large-cell lymphoma were retrospectively evaluated. Neoplastic lymphocytes were identified based on cell size, nuclear size, chromatin pattern, and the presence of nucleoli. Positive specimens were defined as having >= 10% neoplastic lymphocytes. Two groups were established based on the presence or absence of lymphoma in the bone marrow. Variables (positive blood smear, HCT, platelet count, and total and differential WBC counts) were evaluated to determine if they were predictive of bone marrow involvement using univariate and multivariate logistic models. RESULTS: Thrombocytopenia and the presence of > 10% neoplastic lymphocytes on blood smears were identified as significant variables for predicting the presence of bone marrow involvement. When considered independently, either a positive blood smear or thrombocytopenia had low sensitivity (60%) and moderate specificity (89% and 87%, respectively). Sensitivity increased when these variables were evaluated together (80%). CONCLUSIONS: In dogs with multicentric large-cell lymphoma, thrombocytopenia or the presence of neoplastic lymphocytes in circulation is suggestive of bone marrow involvement, but not definitive. Normal peripheral blood findings do not exclude the possibility of lymphoma in the bone marrow. PMID- 25138383 TI - Possibilities for discrimination between chewing of coca leaves and abuse of cocaine by hair analysis including hygrine, cuscohygrine, cinnamoylcocaine and cocaine metabolite/cocaine ratios. AB - Contrary to the illegal use of any form of manufactured cocaine, chewing of coca leaves and drinking of coca tea are allowed and are very common and socially integrated in several South American countries. Because of this different legal state, an analytical method for discrimination between use of coca leaves and abuse of processed cocaine preparations is required. In this study, the applicability of hair analysis for this purpose was examined. Hair samples from 26 Argentinean coca chewers and 22 German cocaine users were analysed for cocaine (COC), norcocaine (NC), benzoylecgonine (BE), ecgonine methyl ester (EME), cocaethylene (CE), cinnamoylcocaine (CIN), tropacocaine (TRO), cuscohygrine (CUS) and hygrine (HYG) by hydrophilic interaction liquid chromatography (HILIC) in combination with triplequad mass spectrometry (MS/MS) and hybrid quadrupole time of-flight mass spectrometry (QTOF-MS). The following concentrations (range, median, ng/mg) were determined in hair of the coca chewers: COC 0.085-75.5, 17.0; NC 0.03-1.15, 0.12; BE 0.046-35.5, 6.1; EME 0.014-6.0, 0.66; CE 0.00-13.8, 0.38; CIN 0.005-16.8, 0.79; TRO 0.02-0.16, 0.023; CUS 0.026-26.7, 0.31. In lack of a reference substance, only qualitative data were obtained for HYG, and two metabolites of CUS were detected which were not found in hair of the cocaine users. For interpretation, the concentrations of the metabolites and of the coca alkaloids in relation to cocaine were statistically compared between coca chewers and cocaine users. By analysis of variance (ANOVA) significant differences were found for all analytes (alpha = 0.000 to 0.030) with the exception of TRO (alpha = 0.218). The ratios CUS/COC, CIN/COC and EME/COC appeared to be the most suitable criteria for discrimination between both groups with the means and medians 5-fold to 10-fold higher for coca chewers and a low overlap of the ranges between both groups. The same was qualitatively found for HYG. However, these criteria cannot exclude cocaine use in addition to coca chewing. In this regard screening for typical cutting agents can be helpful and led to the detection of levamisole (21*), lidocaine (6*) and paracetamol (3*) in the 22 samples from German cocaine users, whereas no levamisole, lidocaine (3*) and paracetamol (1*) were found in hair from the Argentinean coca chewers. These criteria have to be confirmed for South American cocaine consumers including smokers of coca paste and may be different because of different composition of the drug and other use habits. PMID- 25138385 TI - Absorption spectrophotometric, fluorescence and quantum chemical investigations on non-covalent interaction between PC70BM and designed diporphyrin in solution. AB - Present work reports the photophysical insights on supramolecular interaction of a C70 derivative, namely, [6,6]-phenyl C71 butyric acid methyl ester (PC70BM), with two designed diporphyrin molecules having dithiophene (1) and carbazole (2) spacer in toluene and benzonitrile. Both absorption spectrophotometric and steady state fluorescence investigations reveal efficient complexation of PC70BM with 1 and 2 in both toluene and benzonitrile. The magnitude of average value of binding constant, viz., Kav, for the complexes of PC70BM with 1 and 2 in toluene (benzonitrile) are estimated to be 2.185 * 10(3)dm(3)mol(-1) (3.215 * 10(3)dm(3)mol(-1)) and 10.180 * 10(3)dm(3)mol(-1) (25.405 * 10(3)dm(3)mol(-1)), respectively. Selectivity in binding for the complexation process of PC70BM with 1 and 2 is estimated to be ~4.6 and ~7.90 as observed in toluene and benzonitrile, respectively. The complexation between PC70BM and diporphyrin is well accounted by a theoretical model which takes into account the electronic subsystems of both acceptor and donor. Ab initio calculations in vacuo establish that size selective orientation pattern of PC70BM towards the cavity of diporphyrin dictates the magnitude of binding and electronic structure of the PC70BM/diporphyrin complexes. PMID- 25138386 TI - Beyond barriers: fundamental 'disconnects' underlying the treatment of breast cancer patients' sexual health. AB - Sexual health concerns represent one of the most frequently experienced and longest-lasting effects of breast cancer treatment, but research suggests that service providers rarely discuss sexual health with their patients. Existing research examining barriers to addressing patients' sexual health concerns has focused on discrete characteristics of the provider-patient interaction without considering the broader context in which these interactions occur. Drawing on the experiences of 21 breast cancer survivors, this paper explores three ways in which fundamental cultural and structural characteristics of the cancer care system in the USA may prevent breast cancer survivors from addressing their sexual health concerns, including: (1) when patients discussed sexual health with their providers, their providers approached sexuality as primarily physical, while participants experienced complex, multidimensional sexual health concerns; (2) specialisation within cancer care services made it difficult for patients to identify the appropriate provider to address their concerns; and (3) the structure of cancer care literally disconnects patients from the healthcare system at the time when sexual side effects commonly emerged. These data suggest that addressing breast cancer survivors' sexual health concerns requires a multifaceted approach to health systems change. PMID- 25138387 TI - [Listeria monocytogenes and its relationship with non-biological therapy in inflammatory bowel disease]. PMID- 25138388 TI - Age-related pattern and monocyte-acquired haemozoin associated production of erythropoietin in children with severe malarial anaemia in Ghana. AB - BACKGROUND: Malaria continues to be a global health challenge, affecting more than half the world's population and causing approximately 660,000 deaths annually. The majority of malaria cases are caused by Plasmodium falciparum and occur in sub-Saharan Africa. One of the major complications asscociated with malaria is severe anaemia, caused by a cycle of haemoglobin digestion by the parasite. Anaemia due to falciparum malaria in children has multifactorial pathogenesis, which includes suppression of bone marrow activity. Recent studies have shown that haemozoin, which is a by-product of parasite haemoglobin digestion, may play an important role in suppression of haemoglobin production, leading to anaemia. In this study we correlated the levels of erythropoietin (EPO), as an indicator of stimulation of haemoglobin production, to the levels of monocyte acquired haemozoin in children with both severe and uncomplicated malaria. There was a significantly negative correlation between levels of haemozoin-containing monocytes and EPO, which may suggest that haemozoin suppresses erythropoiesis in severe malaria. A multiple linear regression analysis and simple bar was used to investigate associations between various haematological parameters. METHODS: To examine the levels of erythropoietin in the age categories, the levels of erythropoietin was measured using a commercial Enyme-Linked Immunosorbent Assay (ELISA). Giemsa-stained blood smears were used to determine percentage pigment containing monocytes. The haemozoin containing monocytes was expressed as a percentage of the total number of monocytes. To obtain the number of haemozoin containing monocytes/MUL the percentage of haemozoin containing monocytes was multiplied by the absolute number of monocytes/MUL from the automated haematology analyzer. RESULTS: The levels of erythropoietin in younger children (<3 years) was significantly higher than in older children with a similar degree of malaria anaemia (Hb levels) (p < 0.005). Haemozoin-containing monocytes were relatively higher in severe malaria anaemia patients compared to those with uncomplicated malaria (p < 0.001). CONCLUSIONS: Age purportedly has a direct effect on background levels of erythropoietin. With corresponding decreased levels of erythropoietin in older children with the same degree of severe malarial anaemia, conceivably, the bone marrows of younger children with acute malaria may be less sensitive to erythropoietin. PMID- 25138389 TI - A health-economic analysis of diagnosis and treatment of obstructive sleep apnea with continuous positive airway pressure in relation to cardiovascular disease. The Greek experience. AB - PURPOSE: Obstructive sleep apnea syndrome (OSAS) is common in adult population and it is associated with increased morbidity and mortality, especially due to cardiovascular disease (CVD). Both diagnosis, based on polysomnography, and treatment with continuous positive airway pressure (CPAP), carry a potentially high cost. The present study aims to analyze the cost-effectiveness of CPAP treatment versus no treatment, in the long-term, as it examines the effect of this treatment on the incidence of CVD. METHODS: A Markov model was constructed to observe the disease evolution in patients with OSAS based on published evidence. Data on treatment costs were collected from public hospitals in Greece. Within each cycle of the model, each patient may remain free of CVD, may develop CVD, may die due to a cause related to CVD, or may die from other causes. The model begins at the age of 55 years in a severe OSAS patient (apnea-hypopnea index >=30/h) and lasts for 45 years. RESULTS: Within the limitation of the model, CPAP was found to be a cost-effective strategy versus no treatment, due to the reduction of the cost for the CVD treatment, when the analysis was restricted to the male population. Moreover, CPAP was found to be clinically more effective than no treatment, as it increases life expectancy in both males and females. CONCLUSIONS: CPAP was found to be clinically more effective therapy than no treatment in relation to CVD and a cost-effective strategy in males with severe OSAS. PMID- 25138390 TI - The role of pharmacies and pharmacists in managing controlled substance dispensing. AB - The epidemic of prescription opioid-related morbidity and mortality demonstrates the need for a fresh, open, and balanced approach to managing pain while minimizing adverse personal and public health outcomes. Interventions by pharmacists in situations in which prescriptions are felt to be inappropriate have raised the ire of prescribers who feel their professional judgment is being questioned and their time is being usurped from patient care. Pharmacists, however, represent an important check and balance in the opioid analgesic prescribing chain, and prescribers should embrace their involvement and recognize that the time and effort of the pharmacist are directed at improving care of individual patients and keeping a watchful eye on the public health. Pharmacies need to keep a mindful eye toward professional practices of physicians and use noninvasive means, such as database inquiries, prior to directly contacting a prescriber. Collaboration is the most professional approach that can be taken to assure that our joint priority of caring for patients in distress will be accomplished effectively and safely. PMID- 25138391 TI - Lung cancer screening with low-dose CT (LDCT), or when a public health intervention is beyond the patient's benefit. PMID- 25138392 TI - Passive smoking assessed by salivary cotinine and self-report in relation to cause-specific mortality: 17-year follow-up of study participants in the UK Health and Lifestyle Survey. AB - BACKGROUND: Evidence that passive smoking is a risk factor for cardiovascular disease and selected cancers is largely derived from studies in which this exposure is self-reported. Objective assessment using biochemical techniques may yield a more accurate estimate of risk, although each approach has its strengths and weaknesses. We examined the association of salivary cotinine, a widely utilised biomarker for passive smoking, and self-reported passive smoking in the home, with mortality from all causes, cardiovascular disease and all cancers combined. METHODS: In 1992, investigators on the UK Health and Lifestyle Survey collected data on salivary cotinine, self-reported smoking (direct and passive) and a range of covariates in 3731 men and women aged 25 years and over. Mortality was ascertained using linkage to national death records. RESULTS: Analyses were based on 2523 individuals (1433 [57%] women) who classified themselves as non smokers (never and former). Seventeen years of follow-up gave rise to 588 deaths (253 from cardiovascular disease and 146 from cancer). In men, adjusted hazard ratios (HR) for the association between cotinine levels (1.3-15.0 [high] vs <=0.3 [low] ng/mL) and the various mortality outcomes were weak for total mortality (HR; 95% CI: 1.22; 0.91 to 1.64) and cardiovascular disease (1.25; 0.78 to 1.99) and absent for all cancers combined (1.10; 0.61 to 2.00). Corresponding associations were generally stronger when self-reported passive smoking (some vs none) was the exposure of interest: 1.53 (1.12 to 2.08), 1.88 (1.20 to 2.96) and 1.58 (0.85 to 2.93). The pattern of association for women in both sets of analyses was less consistent. CONCLUSIONS: In men in the present study, compared with our biochemical marker of passive smoking, cotinine, mortality was generally more consistently associated with self-reported passive smoking. PMID- 25138393 TI - Goals and grades for medical teachers. PMID- 25138394 TI - [Re: The animal welfare act should be expanded to include children]. PMID- 25138395 TI - [G.E. Berge replies]. PMID- 25138396 TI - [Re: Wise suggestions about abortion referral]. PMID- 25138397 TI - [Re: The psychiatrist role in crisis]. PMID- 25138398 TI - [Re: Renal sympathetic denervation in treatment-resistant hypertension]. PMID- 25138400 TI - [Dental health when using bisphosphonates against breast cancer]. PMID- 25138401 TI - [Differences in treatment of stroke]. PMID- 25138402 TI - [Medication Reconciliation--important measure for better treatment]. PMID- 25138404 TI - [Citation analysis of research articles from Norwegian health enterprises, 2005 2011]. AB - BACKGROUND: The citation frequency of a publication is often interpreted as an expression of its scientific impact. Previous citation analyses of Norwegian medical research have either focused on universities and university hospitals or on subject areas at the national level. Such analyses have paid little attention to other health enterprises, despite a strong increase in their research activity during the last decade. MATERIAL AND METHOD: For all health enterprises with more than 25 publications in the Web of Science during the period 2005-2011 we have calculated field normalized citation indexes at the institution and subject levels. RESULTS: On the whole, research undertaken by the health enterprises is frequently cited, and some medium-sized health enterprises stand out in terms of their high average citation indexes: Helse Stavanger Health Enterprise, Diakonhjemmet Hospital and Helse Nord-Trondelag Health Enterprise, although Oslo University Hospital Health Enterprise and Helse Bergen Health Enterprise account for more than half of the most cited articles. INTERPRETATION: In citation analyses at the aggregated level, highly and infrequently cited research groups/departments may balance each other. This appears to be the case in the largest health enterprises. Some medium-sized health enterprises that have a more concentrated research portfolio will thus accumulate higher average citation indexes than the largest university hospitals. PMID- 25138405 TI - [Two migrated intrauterine devices]. PMID- 25138406 TI - [A man in his forties with swelling in both orbits]. AB - Erdheim-Chester disease. A multi-disiplinary challenge. The histiocytoses are a diverse, but rare group of disorders with symptoms affecting many organs, varying from self-limiting, localised lesions to disseminated multi-organ disease. The diagnostic challenges are illustrated and discussed in the following case. CASE REPORT: A man in his forties was admitted to hospital due to pain in his right eye and visual disturbances. MRI imaging detected a mass in his right orbit and a minor mass in his left orbit. The histological results of the mass in his right orbit revealed an inflammatory process with lymphocytes and macrophages and no sign of vasculitis, infection or malignancy. The diagnosis pseudotumor orbita was made and treatment with corticosteroids was initiated. He did not respond to corticosteroids or radiotherapy and increasing symptoms necessitated rehospitalisation. Further tests disclosed a multisystem disease which affected the aorta, skeleton, lung, heart and kidney. The biopsy was reconsidered and the disease was classified as a histiocytosis with CD68 positive and CD1a negative cells. The diagnosis Erdheim-Chester was given, about 14 months after the initial hospitalisation. Treatment with interferon alpha was started. PMID- 25138407 TI - [Goals and means in medical education]. PMID- 25138408 TI - [Hidden learning within the medical education--what books do not tell]. PMID- 25138409 TI - [Professionalism does not come by itself]. PMID- 25138410 TI - Lack of earthing in Cambodia. PMID- 25138411 TI - [Watchdog in medical records]. PMID- 25138423 TI - Colloid cysts: endoscopic or microsurgical resection? PMID- 25138424 TI - Perspectives: has intraoperative near infrared indocyanine green video angiography replaced formal angiography in aneurysm surgery? PMID- 25138426 TI - Does a test impact on a patient's life many years from now? PMID- 25138425 TI - Haploidentical hematopoietic stem cell transplantation in adults with Philadelphia-negative acute lymphoblastic leukemia: no difference in the high- and low-risk groups. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective post-consolidation therapy and curative option for adult patients with Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL) in first complete remission (CR1). A human leukocyte antigen (HLA)-haploidentical related donor (haplo-RD) is one of the most important alternative sources for those without HLA-identical sibling donor (ISD). The present study aimed to evaluate the outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in adult Ph-negative ALL CR1 patients (n = 183). We produced an unmanipulated haplo-HSCT protocol including granulocyte colony stimulating factor (G-CSF) for all donors, intensive immune suppression, anti-thymocyte globulin, and combination of G-CSF-primed bone marrow harvest and G-CSF-mobilized peripheral blood stem cells harvest as the source of stem cell grafts. The median age for high-risk versus low-risk groups were 29 versus 23 years. Three-year incidences of relapse mortality and nonrelapse mortality for high-risk versus low risk groups were 7.1% versus 11.1% (p = 0.498) and 18.0% versus 16.2% (p = 0.717), respectively. Three-year probabilities of disease-free survival and overall survival for high-risk versus low-risk groups were 67.6% versus 68.2% (p = 0.896) and 74.9% versus 72.7% (p = 0.981), respectively. Multivariate analysis showed that limited cGVHD and a lower pre-HSCT comorbidity burden were associated with better outcomes. In summary, comparable outcomes were observed among high- and low-risk Ph-negative ALL CR1 patients after haplo-HSCT. Haplo-RD could be considered for adults with Ph-negative ALL in CR1 as an important alternative source of donors in cases when no ISD is available. PMID- 25138428 TI - A hospital-based survey on food allergy in the population of Kolkata, India. AB - BACKGROUND: Food allergy is increasing worldwide, and Asian countries are not the exception. Still, ample data are lacking in India. We conducted a cross-sectional study in a metropolis of Eastern India to record the presence of food allergy among the local population. METHODS: The prevalence of food allergy was investigated among patients reporting to The Institute of Child Health and Mediland Diagnostics in Kolkata, India. A total of 5,161 patients were subdivided into 3 age groups and surveyed accordingly. The evaluation was conducted via a questionnaire and a skin prick test. RESULTS: Among the 5,161 patients tested, 4,160 showed a positive response to one or more food items. Banana (32%), brinjal (29%), wheat (22%), and egg (23%) were found to be dominant allergens. Sixty three percent of patients with a family history of allergy showed either a sudden or an insidious mode of onset, whereas the remaining 37% suffered insidious allergic symptoms with no record of a family history of allergy. Skin rashes, cough, and sneezing were the major symptoms observed. Patients in the age group of 15-40 years were the most susceptible. CONCLUSION: It has been observed that certain specific foods consumed in specific regions cause allergies that are unique to their respective populations. In the present study, the most commonly consumed foods in the studied area, e.g. banana, brinjal, wheat, and egg, had severe effects on the local population. Complementary studies in other countries as well as in other parts of India will allow us to gain further insight into this fact. Some other influencing factors were found to be genetics, cultural habits, and occupation. Avoidance of the allergy-causing food is the best way to deal with food allergy. PMID- 25138427 TI - Molecular imaging to predict ventricular arrhythmia in heart failure. AB - Ventricular tachycardia (VT) is a major cause of sudden cardiac death (SCD) in patients with heart failure (HF). Left ventricular ejection fraction (LVEF) and heart failure class according to the New York Heart association (NYHA) are in most common use to identify patients that may benefit from implantable cardioverter defibrillator (ICD) therapy. But during 3 years of follow up only 35% of patients receive appropriate ICD action. Therefore, there is a continued need for refinement of selection criteria for ICD implantation. In this regard, molecular imaging of the autonomic nervous system, which plays a central role in HF progression and cardiac electro-mechanical regulation, can make a substantial contribution. This article reviews the currently available literature concerning the value of molecular neuronal cardiac imaging for prediction of ventricular arrhythmias in HF patients. PMID- 25138429 TI - Poor dietary diversity and low nutrient density of the complementary diet for 6- to 24-month-old children in urban and rural KwaZulu-Natal, South Africa. AB - Infants and toddlers have high nutritional requirements relative to body size but consume small amounts of food and therefore need nutrient-dense complementary foods. A cross-sectional study included children aged 6-24 months, stratified in three age categories (6-11 months, 12-17 months and 18-24 months) and randomly selected from an urban (n = 158) and a rural (n = 158) area, both of low socio economic status, in the KwaZulu-Natal Province of South Africa. Dietary diversity and nutrient density of the complementary diet (excluding breast milk and formula milk) based on a repeated 24-h dietary recall was assessed. For breastfeeding children, nutrient density of the complementary diet was adequate for protein, vitamin A and vitamin C; and inadequate for 100% of children for zinc, for >80% of children for calcium, iron and niacin; and between 60% and 80% of children for vitamin B6 and riboflavin. Urban/rural differences in density for animal and plant protein, cholesterol and fibre occurred in 18-24-month-old children. Fewer than 25% of children consumed >=4 food groups, with no urban/rural differences. Higher dietary diversity was associated with higher nutrient density for protein and several of the micronutrients including calcium, iron and zinc. The poor nutrient density for key micronutrients can probably be ascribed to lack of dietary variety, and little impact of mandatory fortification of maize meal/wheat flour on infants/toddlers' diet. Targeted strategies are needed to enable mothers to feed their children a more varied diet. PMID- 25138430 TI - Is the incidence of malignancy increased in patients with sarcoidosis? A systematic review and meta-analysis. AB - A possible causal relationship between sarcoidosis and malignancy has been the subject of debates for decades. To better understand this association, we conducted a systematic review and meta-analysis of cohort studies that reported relative risk, hazard ratio or standardized incidence ratio with 95% confidence interval (CI) comparing the incidence of malignancy in patients with sarcoidosis versus non-sarcoidosis participants. Pooled risk ratios (RR) and 95% CI were calculated using a random-effect, generic inverse variance methodology. Five studies were identified and included in our data analyses. The pooled RR of malignancy in patients with sarcoidosis was 1.21 (95% CI: 1.04-1.40). However, when we performed a sensitivity analysis that included only studies that compared the incidence of malignancy after the first year of the diagnosis of sarcoidosis with the incidence of malignancy after the first year of index date for non sarcoidosis controls, the pooled risk ratio decreased and did not reach statistical significance (RR 1.13, 95% CI: 0.97-1.32). Furthermore, analysis for publication bias has suggested that publication bias in favour of positive studies may be present. In conclusion, after accounting for possible detection bias and publication bias, there does not appear be a significant association between sarcoidosis and malignancy. PMID- 25138431 TI - A review of the indirect protection of younger children and the elderly through a mass influenza vaccination program in Japan. AB - In the past, Japan's strategy for controlling influenza was to vaccinate schoolchildren based on the theory that this could reduce influenza epidemics in the community, and a special program to vaccinate schoolchildren against influenza was begun in 1962. However, the program was discontinued in 1994 because of lack of evidence that it had limited the spread of influenza in the community. In 2001, it was reported that a clear decrease in excess mortality had coincided with the timing of the schoolchild vaccination program. This decrease could have potentially occurred because elderly people were protected by herd immunity generated by the program. Moreover, the program protected the younger siblings of schoolchildren against influenza-associated encephalopathy. Finally, the program was effective in reducing the number of class cancellations and absenteeism from school. During the period when the program was in effect, Japanese schoolchildren served as a barrier against influenza in the community. PMID- 25138432 TI - Variation in plant defences among populations of a range-expanding plant: consequences for trophic interactions. AB - Although plant-herbivore-enemy interactions have been studied extensively in cross-continental plant invasions, little is known about intra-continental range expanders, despite their rapid spread globally. Using an ecological and metabolomics approach, we compared the insect performance of a generalist and specialist herbivore and a parasitoid, as well as plant defence traits, among native, exotic invasive and exotic non-invasive populations of the Turkish rocket, Bunias orientalis, a range-expanding species across parts of Eurasia. In the glasshouse, the generalist herbivore, Mamestra brassicae, and its parasitoid, Microplitis mediator, performed better on non-native than on native plant populations. Insect performance did not differ between the two non-native origins. By contrast, the specialist herbivore, Pieris brassicae, developed poorly on all populations. Differences in trichome densities and in the metabolome, particularly in the family-specific secondary metabolites (i.e. glucosinolates), may explain population-related variation in the performance of the generalist herbivore and its parasitoid. Total glucosinolate concentrations were significantly induced by herbivory, particularly in native populations. Native populations of B. orientalis are generally better defended than non-native populations. The role of insect herbivores and dietary specialization as a selection force on defence traits in the range-expanding B. orientalis is discussed. PMID- 25138433 TI - Overestimation of body size in eating disorders and its association to body related avoidance behavior. AB - Body-related avoidance behavior, e.g., not looking in the mirror, is a common feature of eating disorders. It is assumed that it leads to insufficient feedback concerning one's own real body form and might thus contribute to distorted mental representation of one's own body. However, this assumption still lacks empirical foundation. Therefore, the aim of the present study was to examine the relationship between misperception of one's own body and body-related avoidance behavior in N = 78 female patients with Bulimia nervosa and eating disorder not otherwise specified. Body-size misperception was assessed using a digital photo distortion technique based on an individual picture of each participant which was taken in a standardized suit. In a regression analysis with body-related avoidance behavior, body mass index and weight and shape concerns as predictors, only body-related avoidance behavior significantly contributed to the explanation of body-size overestimation. This result supports the theoretical assumption that body-related avoidance behavior makes body-size overestimation more likely. PMID- 25138434 TI - Quercetin induces mitochondrial-derived apoptosis via reactive oxygen species mediated ERK activation in HL-60 leukemia cells and xenograft. AB - Quercetin is a plant-derived bioflavonoid that was recently shown to have multiple anticancer activities in various solid tumors. Here, novel molecular mechanisms through which quercetin exerts its anticancer effects in acute myeloid leukemia (AML) cells were investigated. Results from Western blot and flow cytometric assays revealed that quercetin significantly induced caspase-8, caspase-9, and caspase-3 activation, poly ADP-ribose polymerase (PARP) cleavage, and mitochondrial membrane depolarization in HL-60 AML cells. The induction of PARP cleavage by quercetin was also observed in other AML cell lines: THP-1, MV4 11, and U937. Moreover, treatment of HL-60 cells with quercetin induced sustained activation of extracellular signal-regulated kinase (ERK), and inhibition of ERK by an ERK inhibitor significantly abolished quercetin-induced cell apoptosis. MitoSOX red and 2',7'-dichlorofluorescin fluorescence, respectively, showed that mitochondrial superoxide and intracellular peroxide levels were higher in quercetin-treated HL-60 cells compared with the control group. Moreover, both N acetylcysteine and the superoxide dismutase mimetic, MnTBAP, reversed quercetin induced intracellular reactive oxygen species production, ERK activation, and subsequent cell death. The in vivo xenograft mice experiments revealed that quercetin significantly reduced tumor growth through inducing intratumoral oxidative stress while activating the ERK pathway and subsequent cell apoptosis in mice with HL-60 tumor xenografts. In conclusions, our results indicated that quercetin induced cell death of HL-60 cells in vitro and in vivo through induction of intracellular oxidative stress following activation of an ERK mediated apoptosis pathway. PMID- 25138436 TI - Gadolinium- or iodine-based contrast media: which choice? PMID- 25138435 TI - Role of two types of angiotensin II receptors in colorectal carcinoma progression. AB - Angiotensin II (Ang-II) is a bioactive peptide associated closely with the progression and metastasis of colorectal cancer (CRC). We examined the expression and role of 2 Ang-II receptor types in 20 cases of CRC. Ang-II type 1 receptor (AT1R) protein was localized to the plasma membrane, whereas Ang-II type 2 receptor (AT2R) protein was localized to the nuclei. AT1R expression showed a direct correlation with tumor stage and liver metastasis, whereas AT2R expression showed an inverse correlation. A knockdown study of the AT1R or AT2R with Ang-II treatment was performed to reveal their individual roles in a mouse rectal cell line CMT93, which expresses both Ang-II receptor types. AT2R knockdown showed that the AT1R was associated with tumor growth, survival, invasion and VEGF-A secretion in CMT93 cells in a dose-dependent manner. In contrast, AT1R knockdown showed that the AT2R was associated with increased VEGF-A secretion at low Ang-II concentrations, whereas high concentrations of Ang-II inhibited tumor growth, survival, invasion and VEGF-A secretion. Thus, the AT1R showed a monophasic protumoral effect, while the AT2R showed a biphasic amphitumoral effect. Our findings suggest that a high angiotensinogen condition in the liver might evoke the antitumoral role of the AT2R in CRC cells. PMID- 25138438 TI - Commercially available mobile phone headache diary apps: a systematic review. AB - BACKGROUND: Headache diaries are often used by headache sufferers to self-monitor headaches. With advances in mobile technology, mobile electronic diary apps are becoming increasingly common. OBJECTIVE: This review aims to identify and evaluate all commercially available mobile headache diary apps for the two most popular mobile phone platforms, iOS and Android. METHODS: The authors developed a priori a set of 7 criteria that define an ideal headache diary app intended to help headache sufferers better understand and manage their headaches, while providing relevant data to health professionals. The app criteria were intended as minimum requirements for an acceptable headache diary app that could be prescribed by health care professionals. Each app was evaluated and scored against each criterion. RESULTS: Of the 38 apps identified, none of the apps met all 7 app criteria. The 3 highest scoring apps, meeting 5 of the app criteria, were iHeadache (developed by Better QOL), ecoHeadache (developed by ecoTouchMedia), and Headache Diary Pro (developed by Froggyware). Only 18% of the apps were created with scientific or clinical headache expertise and none of the apps reported on psychometric properties. CONCLUSIONS: Despite the growing market and demand, there is a concerning lack of scientific expertise and evidence base associated with headache diary apps. PMID- 25138437 TI - OsABCG15 encodes a membrane protein that plays an important role in anther cuticle and pollen exine formation in rice. AB - KEY MESSAGE: An ABC transporter gene ( OsABCG15 ) was proven to be involved in pollen development in rice. The corresponding protein was localized on the plasma membrane using subcellular localization. Wax, cutin, and sporopollenin are important for normal development of the anther cuticle and pollen exine, respectively. Their lipid soluble precursors, which are produced in the tapetum, are then secreted and transferred to the anther and microspore surface for polymerization. However, little is known about the mechanisms underlying the transport of these precursors. Here, we identified and characterized a member of the G subfamily of ATP-binding cassette (ABC) transporters, OsABCG15, which is required for the secretion of these lipid-soluble precursors in rice. Using map based cloning, we found a spontaneous A-to-C transition in the fourth exon of OsABCG15 that caused an amino acid substitution of Thr-to-Pro in the predicted ATP-binding domain of the protein sequence. This osabcg15 mutant failed to produce any viable pollen and was completely male sterile. Histological analysis indicated that osabcg15 exhibited an undeveloped anther cuticle, enlarged middle layer, abnormal Ubisch body development, tapetum degeneration with a falling apart style, and collapsed pollen grains without detectable exine. OsABCG15 was expressed preferentially in the tapetum, and the fused GFP-OsABCG15 protein was localized to the plasma membrane. Our results suggested that OsABCG15 played an essential role in the formation of the rice anther cuticle and pollen exine. This role may include the secretion of the lipid precursors from the tapetum to facilitate the transfer of precursors to the surface of the anther epidermis as well as to microspores. PMID- 25138439 TI - Tethering metal ions to photocatalyst particulate surfaces by bifunctional molecular linkers for efficient hydrogen evolution. AB - A simple and versatile method for the preparation of photocatalyst particulates modified with effective cocatalysts is presented; the method involves the sequential soaking of photocatalyst particulates in solutions containing bifunctional organic linkers and metal ions. The modification of the particulate surfaces is a universal and reproducible method because the molecular linkers utilize strong covalent bonds, which in turn result in modified monolayer with a small but controlled quantity of metals. The photocatalysis results indicated that the CdS with likely photochemically reduced Pd and Ni, which were initially immobilized via ethanedithiol (EDT) as a linker, were highly efficient for photocatalytic hydrogen evolution from Na2S-Na2SO3-containing aqueous solutions. The method developed in this study opens a new synthesis route for the preparation of effective photocatalysts with various combinations of bifunctional linkers, metals, and photocatalyst particulate materials. PMID- 25138440 TI - Pathologic changes associated with suspected hypovitaminosis A in amphibians under managed care. AB - Vitamin A deficiency is a recently recognized nutritional disease in amphibians fed insect-based diets. The classic pathologic lesion that has been associated with hypovitaminosis A in amphibians is squamous metaplasia of the lingual and oral mucosa. In an attempt to further characterize the range of lesions that may be associated with vitamin A deficiency, we reviewed archived amphibian necropsy reports from three facilities. As previously reported, the tongue was the most commonly affected site in animals presenting with squamous metaplasia. However, metaplastic changes were also observed in a variety of locations that included the oral cavity, nasal cavity, pharynx, esophagus, stomach, cloaca, skin, urinary bladder, ureter, and reproductive tract. In addition, species and age-specific differences were noted in the development of squamous metaplasia. This review highlights the need to establish standardized guidelines for optimal postmortem tissue sampling of amphibians in order to maximize the accurate diagnosis of pathologic lesions that may be associated with hypovitaminosis A. Zoo Biol. 33:508-515, 2014. (c) 2014 Wiley Periodicals Inc. PMID- 25138442 TI - Multifunctional Ag-decorated porous TiO2 nanofibers in dye-sensitized solar cells: efficient light harvesting, light scattering, and electrolyte contact. AB - Designing the photoanode structure in dye-sensitized solar cells (DSSCs) is vital to realizing enhanced power conversion efficiency (PCE). Herein, novel multifunctional silver-decorated porous titanium dioxide nanofibers (Ag/pTiO2 NFs) made by simple electrospinning, etching, and chemical reduction processes are introduced. The Ag/pTiO2 NFs with a high surface area of 163 m(2) g(-1) provided sufficient dye adsorption for light harvesting. Moreover, the approximately 200 nm diameter and rough surface of the Ag/pTiO2 NFs offered enough light scattering, and the enlarged interpores among the NFs in the photoanode also permitted electrolyte circulation. Ag nanoparticles (NPs) were well dispersed on the surface of the TiO2 NFs, which prevented aggregation of the Ag NPs after calcination. Furthermore, a localized surface plasmon resonance effect by the Ag NPs served to increase the light absorption at visible wavelengths. The surface area and amount of Ag NPs was optimized. The PCE of pTiO2 NF-based DSSCs was 27 % higher (from 6.2 to 7.9 %) than for pure TiO2 NFs, whereas the PCE of Ag/pTiO2 NF-based DSSCs increased by about 12 % (from 7.9 to 8.8 %). Thus, the PCE of the multifunctional pTiO2 NFs was improved by 42 %, that is, from 6.2 to 8.8 %. PMID- 25138441 TI - Exogenous salicylic acid activates two signaling arms of the unfolded protein response in Arabidopsis. AB - The unfolded protein response (UPR) is a highly conserved cellular response that prevents abnormal maturation of proteins in the endoplasmic reticulum (ER). The expression of genes encoding ER chaperones is induced during the UPR. In the Arabidopsis UPR, two membrane-bound transcription factors, bZIP60 and bZIP28, activate the expression of those genes. bZIP60 is regulated by unconventional cytoplasmic splicing catalyzed by inositol requiring enzyme 1 (IRE1), which is located in the ER membrane. bZIP28 is regulated by intramembrane proteolysis. Pathogen infection and salicylic acid (SA) have been reported to induce the expression of some UPR genes. Here, we show that UPR genes including BiP3, a marker gene of the Arabidopsis UPR, are induced by exogenous SA treatment and activation of bZIP60 in an IRE1-dependent manner. The induction of gene expression and activation of bZIP60 were independent of NPR1 and HsfB1 under these experimental conditions. We generated antibodies to detect the proteolytic products of bZIP28 after SA treatment. An assay using these antibodies showed that SA activated bZIP28, as well as activating bZIP60 through IRE1. Together, these results show that exogenous SA treatment activates two signaling arms of the Arabidopsis UPR. We propose a possible mechanism of activation of the UPR machinery by SA. PMID- 25138443 TI - Comment on the paper by Kamel et al. Entitled 'Primary cytomegalovirus infection in pregnant Egyptian women confirmed by cytomegalovirus IgG avidity testing'. PMID- 25138445 TI - An iron(II) complex featuring kappa(3) and labile kappa(2)-bound PNP pincer ligands - striking differences between CH2 and NH spacers. AB - Treatment of anhydrous FeCl2 with 2 equiv. of the pincer ligand PNP-Ph afforded the diamagnetic cationic octahedral complex [Fe(kappa(3)-P,N,P-PNP)(kappa(2)-P,N PNP)Cl](+) featuring a kappa(2)-P,N-bound PNP ligand. Preliminary reactivity studies revealed that the kappa(2)-P,N-bound PNP ligand is labile reacting with CO to afford trans-[Fe(PNP-Ph)(CO)2Cl](+). PMID- 25138444 TI - Development and evaluation of a new survey instrument to measure the quality of colorectal cancer screening decisions. AB - BACKGROUND: Guidelines for colorectal cancer screening recommend that patients be informed about options and be able to select preferred method of screening; however, there are no existing measures available to assess whether this happens. METHODS: Colorectal Cancer Screening Decision Quality Instrument (CRC-DQI) includes knowledge items and patients' goals and concerns. Items were generated through literature review and qualitative work with patients and providers. Hypotheses relating to the acceptability, feasibility, discriminant validity and retest reliability of the survey were examined using data from three studies: (1) 2X2 randomized study of participants recruited online, (2) cross-sectional sample of patients recruited in community health clinics, and (3) cross-sectional sample of providers recruited from American Medical Association Master file. RESULTS: 338 participants were recruited online, 94 participants were recruited from community health centers, and 115 physicians were recruited. The CRC-DQI was feasible and acceptable with low missing data and high response rates for both online and paper-based administrations. The knowledge score was able to discriminate between those who had seen a decision aid or not (84% vs. 64%, p < 0.001) and between providers, online patients and clinic patients (89% vs. 74% vs. 41%, p < 0.001 for all comparisons). The knowledge score and most of the goals had adequate retest reliability. About half of the participants received a test that matched their goals (47% and 51% in online and clinic samples respectively). Many respondents who had never been screened had goals that indicated a preference for colonoscopy. A minority of respondents in the online (21%) and in clinic (2%) samples were both well informed and received a test that matched their goals. CONCLUSIONS: The CRC-DQI demonstrated good psychometric properties in diverse samples, and across different modes of administration. Few respondents made high quality decisions about colon cancer screening. PMID- 25138463 TI - Overproduction of geranylgeraniol in Coprinopsis cinerea by the expression of geranylgeranyl diphosphate synthase gene. AB - (E, E, E)-Geranylgeraniol (GGOH) is a valuable ingredient of many perfumes and a valuable precursor for synthesizing pharmaceuticals. In an attempt to increase the GGOH concentration in Coprinopsis cinerea, we demonstrated that the expression of geranylgeranyl diphosphate synthase (ggpps) gene isolated from Taxus x media could promote GGOH production. Furthermore, the concentrations of squalene and ergosterol were measured in the engineered strains. Expectedly, significant decreases of squalene and ergosterol levels were observed in those strains transformed with ggpps gene. This could be explained by the partial redirection of metabolic flux from squalene to GGOH, whose biosynthesis competes for the same precursor with squalene. This work suggested that the expression of ggpps in higher fungi was an effective method for bio-production of GGOH. PMID- 25138464 TI - Pathology of gastric lesions in donkeys: A preliminary study. AB - REASONS FOR PERFORMING STUDY: Donkeys (Equus africanus asinus) are important working animals, particularly in countries where the majority of the population lives below the poverty line. Gastric ulceration has been shown to be common in British donkeys but donkeys from other parts of the world have not been as extensively researched. OBJECTIVES: This study was performed as a preliminary overview of the severity and distribution of gastric lesions in mature donkeys and to document which parasites were present. STUDY DESIGN: Descriptive study of pathological findings. METHODS: Stomachs of 35 mature draught donkeys were examined grossly and histopathology samples taken from 5 regions of the gastric mucosa. RESULTS: Gross examination revealed hyperaemia, oedema, erosions and ulcers in addition to parasitic lesions. Histopathological examination revealed hyperkeratosis, acanthosis, vacuolar degeneration of stratified squamous cells, gastritis, erosions, ulcerations, scarring, hyperactivity of mucus glands, periglandular fibroplasia and parasitic granulomes with infestation by Gasterophilus spp. larvae, Habronema spp. and Draschia megastoma. CONCLUSIONS: In donkeys, ulceration of the nonglandular regions of the stomach is more prominent than the glandular regions and parasitic infestations were frequent. PMID- 25138465 TI - Sonographic appearance of thyroid glands in patients treated with intensity modulated radiotherapy or conventional radiotherapy for nasopharyngeal carcinoma. AB - BACKGROUND: This study aimed to investigate the sonographic appearances of the thyroid glands in nasopharyngeal carcinoma (NPC) patients whose cervical lymph nodes were treated with conventional radiotherapy (RT) or intensity-modulated radiotherapy (IMRT). The post-RT sonographic appearances of the thyroid glands in NPC patients were also correlated with the thyroid function. METHODS: One hundred and three NPC patients who had completed RT of cervical lymph nodes using the anterior cervical field, 30 NPC patients who had completed RT of cervical lymph nodes using IMRT, and 61 healthy subjects were included in the study. Thyroid glands were sonographically assessed for their size, echogenicity, vascularity, and internal architecture. Thyroid function tests were also performed on each subject. RESULTS: In comparison with the patients with abnormal thyroid function, the thyroid glands of the patients with normal thyroid function tended to be homogeneous and to have greater volume and echogenicity index (p < 0.05). Compared with those of the healthy subjects, the thyroid glands of patients previously treated with IMRT and those treated with the anterior cervical field showed significantly lower thyroid volume, lower incidence and number of nodules, and higher vascularity index (p < 0.05). CONCLUSIONS: The patient's history of previous RT should be taken into consideration in the sonographic examination of the thyroid gland post-RT. (c) 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:210-223, 2015. PMID- 25138466 TI - Protonation induced shifting of electron-accepting centers in intramolecular charge transfer chromophores: a theoretical study. AB - A new series of chameleonic molecules containing azulene and benzothiadiazole (BT) were designed and synthesized. In the neutral state, BT functions as an electron accepting center, while upon protonation, the electron accepting center shifts to azulene moieties, leading to a remarkable extension of absorption to the NIR region, i.e. up to 2.5 MUm. The interchange between donor and acceptor characters upon protonation was confirmed by UV-vis-NIR spectral studies and supported by DFT calculations. Furthermore, the HOMO-LUMO level of ICT chromophores could be finely tailored by a different arrangement of azulenes and BTs in the molecules. The interchange between donor and acceptor characters upon protonation provides an alternative yet effective approach to fine tune optical and electronic properties of NIR chromophores. PMID- 25138468 TI - Converting molecular monolayers into functional membranes. AB - Carbon nanomembranes are constructed from monolayers of molecular amphiphiles assembled on a water surface. The floating molecular film is cross-linked to form a mechanically stable nanomembrane. By varying the type of molecules, the surface area, and the exposure condition, the membrane's stiffness, thickness, and permeability can be tailored. PMID- 25138469 TI - Systematic review of literature of cemented femoral components: what is the durability at minimum 20 years followup? AB - BACKGROUND: Cemented femoral total hip arthroplasty may be one of the most successful surgical interventions of all time. However, although results are very encouraging over the early to mid-term followup, relatively few studies have analyzed the durability of these implants beyond 20 years followup. To evaluate the performance of contemporary implants, it is important to understand how previous implants perform at 20 or more years of followup; one way to do this is to aggregate the available data in the form of a systematic review. QUESTIONS/PURPOSES: (1) How durable is cemented femoral fixation in the long term (minimum 20-year followup) with respect to aseptic loosening? (2) Is the durability of cemented femoral fixation dependent on age of the patient? (3) Are the long-term results of the cemented femoral fixation dependent on any identifiable characteristics of the prosthesis such as surface finish? METHODS: A systematic review was performed to identify long-term studies of cemented femoral components. After application of inclusion and exclusion criteria to 1228 articles found with a search in PubMed and EMBASE, 17 studies with a minimum of 20-year followup on cemented femoral components were thoroughly analyzed in an attempt to answer the questions of this review. The quality of the studies reviewed was assessed with the Methodological Index for Nonrandomized Studies (MINORS) instrument. All studies were case series and cohort sizes ranged from 110 to 2000 hips for patients older than 50 years of age and 41 to 93 hips for patients younger than 50 years at the time of surgery. RESULTS: Among the six case series performed in patients older than 50 years of age, survivorship for aseptic loosening of the femoral component ranged from 86% to 98% at 20 years followup. There were no obvious differences for younger patients when analyzing the five studies in patients younger than age 50 years in which survivorship free from aseptic loosening for these studies ranged from 77% at 20 years in one study and 68% to 94% at 25 years in the other studies. Although data pooling could not be performed because of heterogeneity of the studies included here, it appeared that stems with a rougher surface finish did not perform as well as polished stems; survivorship of stems with rougher surface finishes varied between 86% and 87%, whereas those with smoother finishes ranged between 93.5% and 98% at 20 years. CONCLUSIONS: Excellent long-term fixation in both older and younger patients can be obtained with cemented, polished femoral stems. These results provide material for comparison with procedures performed with newer cementing techniques and newer designs, both cemented and cementless, at this extended duration of followup. PMID- 25138470 TI - CORR Insights(r): What sports activity levels are achieved in patients with modular tumor endoprostheses of osteosarcoma about the knee? PMID- 25138471 TI - Are Harris hip scores and gait mechanics related before and after THA? AB - BACKGROUND: Discordance between subjective and objective functional measures hinders the development of new ways to improve THA outcomes. QUESTIONS/PURPOSES: We asked if (1) any kinematic or kinetic gait variables are correlated with preoperative Harris hip scores (HHS), (2) any kinematic or kinetic gait variables are correlated with postoperative HHS, and (3) pre- to postoperative changes in any kinematic or kinetic gait variables are associated with the change in HHS? METHODS: For this retrospective study, an institutional review board-approved data repository that included all individuals who participated in motion analysis research studies was used to identify subjects evaluated before (n=161) and at least 6 months after primary unilateral THA (n=156). Selected kinematic (sagittal plane dynamic hip ROM and kinetic (peak external moments about the hip in the sagittal, frontal, and transverse planes) gait variables were collected at subjects' self-selected normal walking speeds. We used first-order partial correlations to identify relationships between HHS and gait variables, controlling for the influence of speed. RESULTS: Preoperative HHS correlated with hip ROM (R|speed=0.260; p<0.001) and the peak extension moment (R|speed=0.164; p=0.038), postoperative HHS correlated with the peak internal rotation moment (R|speed=0.178; p=0.034), and change in HHS correlated with change in hip ROM (R|speed=0.288; p=0.001) and peak external rotation moment (R|speed=0.291; p=0.002). Similar associations were seen when the HHS pain and function were analyzed separately. CONCLUSIONS: This study identified relationships between a common clinical outcome measure and specific, modifiable gait adaptations that can persist after THA-ROM and transverse plane gait moments. Addressing these aspects of gait dysfunction through focused rehabilitation could be a new strategy for improving clinical outcomes. Prospective studies are needed to evaluate this concept. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Instructions for Authors for a complete description of levels of evidence. PMID- 25138472 TI - What is the effect of advanced age and comorbidity on postoperative morbidity and mortality after musculoskeletal tumor surgery? AB - BACKGROUND: Although the elderly population is increasing rapidly, little information is available regarding how the risk of postoperative mortality and morbidity increases when combined with age and comorbidity burden in patients undergoing musculoskeletal tumor surgery. QUESTIONS/PURPOSES: We evaluated the effect of age and comorbidity burden on the (1) postoperative complication rate and (2) in-hospital mortality rate after musculoskeletal tumor surgery. METHODS: We identified 5716 patients undergoing musculoskeletal tumor surgery during 2007 to 2012 using a Japanese national inpatient database. Logistic regression analyses were performed to examine the relationships of various factors with the rates of mortality and morbidity. RESULTS: The postoperative complication rate (6.7%) was associated with male sex (p = 0.033), age 80 years or older (p = 0.001), tumor located in the lower extremity (p = 0.001) or trunk (p = 0.019), Charlson Comorbidity Index of 4 or greater (p < 0.001), blood transfusion (p < 0.001), and duration of anesthesia of 240 minutes or longer (p < 0.001). The in hospital mortality (0.8%) was related to the Charlson Comorbidity Index of 4 or greater (p < 0.001), blood transfusion (p < 0.001), and high hospital volume (p = 0.016). The morbidity (21.6%; OR, 3.29; p < 0.001) and mortality (4.1%; OR, 5.95; p < 0.001) in patients 80 years or older with a Charlson Comorbidity Index of 4 or greater was increased three and six times, respectively, compared with patients 64 years or younger with no comorbidity. CONCLUSIONS: We found that age and comorbidity burden together greatly increased the risk of morbidity and mortality. Our study showed quantitative evidence that will assist physicians in assessing perioperative risk accurately and provide a more informative explanation to elderly patients undergoing musculoskeletal tumor surgery. LEVEL OF EVIDENCE: Level IV, prognostic study. See the Instructions for Authors for a complete description of levels of evidence. PMID- 25138473 TI - Do patients with insulin-dependent and noninsulin-dependent diabetes have different risks for complications after arthroplasty? AB - BACKGROUND: Patients with diabetes are known to be at greater risk for complications after arthroplasty than are patients without diabetes. However, we do not know whether there are important differences in the risk of perioperative complications between patients with diabetes who are insulin-dependent (Type 1 or 2) and those who are not insulin-dependent. QUESTIONS/PURPOSES: The purpose of our study was to compare (1) medical complications (including death), (2) surgical complications, and (3) readmissions within 30 days between patients with insulin-dependent and noninsulin-dependent diabetes, and with patients who do not have diabetes. METHODS: A total of 43,299 patients undergoing THA or TKA between 2005 and 2011 were selected from the American College of Surgeon's National Surgical Quality Improvement Program's (ACS-NSQIP(r)) database. Generalized linear models were used to assess the relationship between diabetes status and outcomes (no diabetes [n=36,574], insulin dependent [n=1552], and noninsulin dependent [n=5173]). Multivariate models were established adjusting for confounders including age, sex, race, BMI, smoking, steroid use, hypertension, chronic obstructive pulmonary disease, and anesthesia type. Post hoc comparisons between patient groups were made using a Bonferroni correction. RESULTS: Patients who were insulin dependent had increased odds of experiencing a medical complication (OR, 1.6; 95% CI, 1.2-2.0; p<0.001), as did patients who were noninsulin dependent (OR, 1.2; 95% CI, 1.1-1.4; p<0.001). An increased likelihood of 30-day mortality was found only for patients who were insulin dependent (OR, 3.74; 95% CI, 1.6-8.5; p=0.007). However, neither diabetic state was associated with surgical complications. Finally, readmission was found to be independently associated with insulin-dependent diabetes (OR, 1.6; 95% CI, 1.1-2.1; p=0.023). CONCLUSIONS: Patients with insulin-dependent diabetes are most likely to have a medical complication or be readmitted within 30 days after total joint replacement. However, patients who are insulin dependent or noninsulin dependent are no more likely than patients without diabetes to have a surgical complication. Physicians and hospitals should keep these issues in mind when counseling patients and generating risk-adjusted outcome reports. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence. PMID- 25138474 TI - Buccal grafts for urethroplasty in pre-pubertal boys: what happens to the neourethra after puberty? AB - OBJECTIVE: Buccal mucosa grafts (BMG) are often used in complex urethral reconstruction. Following pubertal endogenous androgen stimulation (EAS) in prepubertal boys, there are concerns that the neourethra may not grow proportionally to the phallus. To address the paucity of literature on the topic, this article reports on data for post-pubertal follow up after pre-pubertal BMG urethroplasties (BMGU). PATIENTS AND METHODS: Retrospective chart review of boys who underwent staged BMGU before the age of 12 years at a single referral center between 2000 and 2010 and who were followed up until after puberty. Demographic information, initial meatal location, quality of graft before tubularization, flow rate parameters (FRP) and complications were captured. RESULTS: Of the 137 patients who underwent staged BMGU during the study period, 10 satisfied the inclusion criteria. Mean patient age at first stage BMGU was eight years (range five to eleven years). The mean follow-up was 40.6 months (9-66 months). The grafts were harvested from the cheek and lower lip in seven and three cases, respectively. The mean interval between the first and second stage was 15.8 months (6-87 months). Complications included one urethro-cutaneous fistula and two cases of glanular dehiscence. The final position of the meatus was glanular in nine boys and coronal in one. Importantly, no recurrent ventral curvature (VC) was found during the second stage BMGU or reported after puberty. All patients demonstrated normal maximum flow after puberty (mean 25.7 ml/s). CONCLUSION: Buccal mucosa grafts appear to grow proportionally to the phallus after pubertal EAS. No recurrent VC or inadequate FRP were observed in this series. Despite the small number of subjects, the results are reassuring and support continued use of BMG in the pediatric pre-pubertal population. PMID- 25138475 TI - Primary versus secondary ureteroscopy for pediatric ureteral stones. AB - OBJECTIVE: To evaluate the outcome of primary versus secondary ureteroscopy for pediatric ureteral stones. PATIENTS AND METHODS: A retrospective chart review study that included 66 children aged less than 12 years, who were subdivided into two groups: Group A, which included 42 children who had undergone primary ureteroscopy without pre-stenting; and Group B, which included 24 children who had undergone ureteroscopy after ureteric stenting. Kidneys, ureters and bladder radiographs were done on the first postoperative day to assess the degree of stone clearance and stent position. RESULTS: Age, gender, stone location and stone size were not significantly different between both groups. In Group A, 31 (73.8%) children required ureteric dilation, 13 (31%) had a tight ureter that failed to respond to dilation, 25 (59.5%) displayed complete stone clearance, and of these, 13 (52%) needed postoperative stenting. One child experienced ureteric injury during stone disintegration and was stented for two weeks. Children in Group B experienced a 95.8% complete stone clearance rate, with no ureteric injury reported; postoperative stenting was performed in three (12.5%) children.. CONCLUSION: Secondary ureteroscopy is preferable over primary ureteroscopy in pediatric populations because of a significantly lower need for ureteric dilation, shorter procedure time and better stone clearance rate.. PMID- 25138476 TI - Screening of mutations in NOL3 in a myoclonic syndromes series. PMID- 25138477 TI - Clinical characteristics and outcome of intracerebral hemorrhage in young adults. AB - Data on determinants of prognosis after intracerebral hemorrhage (ICH) in young adults are scarce. Our aim was to identify clinical determinants of prognosis after ICH in adults aged 18-50. We investigated 98 consecutive patients with an ICH, aged 18-50 years, admitted to our hospital between 1980 and 2010. Collected ICH characteristics included presenting symptoms, etiology, location, severity and Glasgow Coma Scale (GCS). Outcomes were case-fatality (death within 30 days), poor functional outcome (modified Rankin Scale >2), long-term mortality and recurrent ICH. We assessed discriminatory power of factors associated with case fatality [area under receiver operating curve (AUC)]. Case-fatality was 20.4 % (n = 20) and well predicted by the GCS (AUC 0.83). Among 30-day survivors, a poor functional outcome at discharge was present in 51.3 %. During a mean follow-up of 11.3 years mortality was only increased in patients aged 40-50 years [standardized mortality ratio 4.8 (95 % CI 2.3-8.6)], but not in patients aged 18 40 years. Recurrent ICH occurred in 6 patients [10-year cumulative incidence 12.2 % (95 % CI 1.5-22.9 %)], all with the index ICH attributable to structural vascular malformations. Prognosis after ICH in young adults is poor, mainly due to high case-fatality, that is well predicted by the GCS. An exception is 30-day survivors <40 years, who have a similar risk of dying as the general population. Recurrence risk is especially present in patients with structural vascular malformations, whereas risk seems to be very low in other patients. PMID- 25138478 TI - Non-convulsive status epilepticus after ischemic stroke: a hospital-based stroke cohort study. AB - To evaluate in the setting of a stroke unit ward the usefulness of a prolonged (>6 h) video-EEG recording (PVEEG) in identifying non-convulsive status epilepticus (NCSE) in patients with an acute ischemic stroke. Predictors of NCSE were also evaluated. Patients with an acute ischemic stroke, referred to our unit, were included in this prospective observational study. A PVEEG recording was implemented after stroke in all patients during the first week: (a) promptly in those exhibiting a clear or suspected epileptic manifestation; (b) at any time during the routine activity in the remaining patients. After the first week, a standard EEG/PVEEG recording was hooked up only in presence of an evident or suspected epileptic manifestation or as control of a previous epileptic episode. NCSE was identified in 32 of the 889 patients (3.6 %) included in the study. It occurred early (within the first week) in 20/32 (62.5 %) patients and late in the remaining 12. Diagnosis was made on the basis of a specific clinical suspect (n = 19, 59.4 %) or without any suspect (n = 13, 40.6 %). In a multivariate analysis, a significant association of NCSE was observed with NIHSS score, infarct size and large atherothrombotic etiology. NCSE is not a rare event after an acute ischemic stroke and a delayed diagnosis could worsen patient prognosis. Since NCSE can be difficult to be diagnosed only on clinical grounds, implementation of a prompt PVEEG should be kept available in a stroke unit whenever a patient develop signs, although subtle, consistent with NCSE. PMID- 25138479 TI - Fetal bronchoscopy as a useful procedure in a case with prenatal diagnosis of congenital microcystic adenomatoid malformation. AB - Massive microcystic congenital cystic adenomatoid malformation (CCAM) and bronchial atresia are associated with a high perinatal mortality secondary to lung hypoplasia and cardiac dysfunction, and fetal intervention should be considered to improve prognosis. Therapeutic options include open fetal surgery with pulmonary resection, fetal sclerotherapy and fetoscopy. We present a case with a severely enlarged left lung without ultrasound signs of dilated airways compatible with the diagnosis of microcystic CCAM, hydrops and severe contralateral lung hypoplasia that was treated successfully at 30 weeks of gestation by fetal bronchoscopy, through which bronchial atresia was identified at the end of the left mainstem bronchi and permeabilized by laser ablation. After fetal surgery, weekly follow-up showed a progressive decrease in the affected lung size and an increase in the contralateral hypoplastic lung size, demonstrating normal dimensions of both lungs at 34 weeks of gestation, reversal of the mediastinal shift, and complete disappearance of hydrops. A healthy neonate was delivered uneventfully at term with no need for respiratory support, and the boy is now doing well at 15 months of age. This report demonstrates that in cases with prenatal diagnosis of large microcystic CCAM, fetal bronchoscopy can be used to refine the diagnosis of bronchial atresia and as a therapeutic tool with good outcome. PMID- 25138480 TI - Mobile teledermatology is a valid method to estimate prevalence of melanocytic naevi in children. AB - The prevalence of melanocytic naevi in children correlates with sun exposure and may serve as an objective population risk indicator of future melanoma incidence. The aim was to investigate if mobile teledermatology could offer a valid methodology compared with standard manual, face-to-face counting of naevi on the back of children. Ninety-seven children aged 7-16 years were enrolled. One dermatologist performed manual naevi counting and imaging of the child's back using an iPhone 4S comprising a safe-coded mobile application. Two other dermatologists independently counted naevi from the images. Cohen's weighted kappa (kappaw) coefficient demonstrated substantial agreement for both dermatologists: kappaw = 0.69 (0.57-0.81 [95% confidence intervals]) and kappaw = 0.78 (0.70-0.86), compared with the manual assessment. Inter-rater reliability was also substantial (kappaw = 0.80 [0.73-0.87]). Use of mobile teledermatology proved valid for estimating naevi prevalence on the back and could provide a more feasible methodology following trends in sun exposure in children. PMID- 25138481 TI - ICEBERG: Intimal Carotid Evaluation Before Echocardiography Reveals Global Vascular Risk. AB - BACKGROUND: There is growing evidence that carotid ultrasonography provides important prognostic information about cardiovascular risk assessment. Our objective was to determine whether abbreviated rapid carotid ultrasonographic screening would reveal important global vascular risk information in statin-naive patients referred for routine transthoracic echocardiography (TTE). METHODS: Abbreviated carotid ultrasonographic imaging was performed in 560 consecutive patients undergoing TTE. The common carotid artery (CCA), the carotid bulb, and the internal carotid artery (ICA) were scanned. Maximal CCA intima-media thickness (IMT) was measured in the far wall. Carotid plaque was defined using the Atherosclerosis Risk in Communities (ARIC) study criteria. RESULTS: Of the 2283 patients who underwent TTE during a 1-year period, a total of 560 patients met inclusion criteria. There were 241 men, with a mean age of 63.2 +/- 12.8 years and a mean CCA IMT of 1.11 +/- 0.48 mm; 61% (147) had carotid plaque. The 319 women had a mean age of 66.3 +/- 10.8 years and a mean CCA IMT of 1.03 +/- 0.36 mm; 62.4% (199) had carotid plaque. All patients with plaque were considered to be at high risk. CONCLUSIONS: Of the 560 consecutive statin-naive patients referred for TTE with no history of vascular disease, a large proportion of both men (61%) and women (62.4%) had carotid plaque, indicating a high risk for vascular events according to the Canadian lipid guidelines. Although such patients are seen in the echocardiography laboratory, the addition of an abbreviated carotid ultrasonographic screening provides important information regarding risk stratification and the implementation of preventive therapy. PMID- 25138482 TI - Is plant-based cardioprotection evidence-based? PMID- 25138483 TI - Stem cell therapy for the treatment of nonischemic cardiomyopathy: a systematic review of the literature and meta-analysis of randomized controlled trials. AB - BACKGROUND: Stem cell (SC) therapy improves left ventricular function and dimensions in ischemic heart disease. Few small-scale trials have studied the effects of SC therapy on nonischemic cardiomyopathy (CMP), the leading cause of heart transplantation in the adults. The objectives were to gain a better insight into the effects of SC therapy for nonischemic CMP by conducting a systematic review of the literature and meta-analysis of randomized controlled trials. METHODS: Medline, EBM Reviews-Cochrane Central Register of Controlled Trials, Embase, and the ClinicalTrials.gov databases were screened for randomized controlled trials involving SC for treatment of nonischemic CMP. Weighted mean differences of improvement of left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) were calculated using a random effect analysis model. RESULTS: Four trials were included in this meta-analysis (244 patients). The weighted mean LVEF improvement was 4.87% (95% confidence interval, 1.32-8.43%) in the treatment group compared with the control group (P = 0.01). The weighted mean decrease of LVEDD in the treatment group was of -2.19 mm (95% confidence interval, -5.69 to 1.30) compared with the control group (P = 0.22). On subgroup analysis, results were similar in studies involving peripheral CD34 positive or bone marrow-derived mononuclear cells (P = 0.33 for subgroup differences). CONCLUSIONS: This is the first meta-analysis to show that for the treatment of nonischemic CMP, SC therapy might improve LVEF, but not LVEDD. Further trials should aim to circumscribe the optimal SC regimen in this setting, and to assess long-term clinical outcomes as primary end points. PMID- 25138484 TI - Purulent pericarditis after transbronchial biopsy. AB - A 28-year-old woman experienced hypotension and unresponsiveness. She had undergone bronchoscopy with needle biopsy 2 weeks before admission to evaluate hilar lymphadenopathy given suspicion of sarcoidosis. She had an elevated white blood cell count of 28,000/MUL and a serum creatinine level of 4.0 mg/dL. Echocardiography showed a large pericardial effusion. Pericardiocentesis resulted in removal of 400 mL of yellow-green purulent material that grew Streptococcus milleri, Prevotella, Veillonella, and Peptostreptococcus species. Pericardiectomy and mediastinal washout were performed. Subsequently, her condition rapidly improved. She returned home after 26 days of admission. At 12-month follow-up, the patient had made a full recovery. PMID- 25138485 TI - Revascularization strategies for coronary disease: art or science? PMID- 25138486 TI - Death and digoxin: stop me if you've heard this one before. PMID- 25138487 TI - Improving efficiency of initial tests for efficacy in smoking cessation drug discovery. AB - INTRODUCTION: One obstacle to rapid development of new smoking cessation medications is the inefficient early clinical evaluation of the efficacy of novel drugs, which inform us as to whether or not to proceed with the greater expense and time of more formal clinical trials. The vast majority of novel drugs fail to show efficacy for cessation only after substantial resources have been spent and, thus, are largely wasted. AREAS COVERED: The author reviews the general limitations in the current typical procedures for initial tests of cessation efficacy in novel drugs. Small, randomized clinical trials often have good validity but may have practical limitations in achieving adequate statistical power to test novel versus placebo treatment conditions. Lab tests of acute drug effects on abstinence symptoms, during brief enforced cessation periods, are practical but have limited clinical predictive validity. EXPERT OPINION: Initial efficacy testing may be more efficient if done using innovative crossover designs that evaluate brief 'practice' quit periods for both active and placebo treatments within the same smokers, recruiting those high in quit motivation. Because this approach would require far fewer subjects and a shorter duration of testing, results could be obtained more rapidly and inexpensively to indicate that a novel drug may, or may not, be sufficiently efficacious as to warrant the greater costs and time of formal randomized clinical trials. PMID- 25138488 TI - Clinical heterogeneity of the C9orf72 genetic mutation in frontotemporal dementia. AB - The C9orf72 genetic mutation represents the most common cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Studies over the last 2 years have revealed a number of key features of this mutation in the fields of clinical neurology, imaging, pathology, and genetics. Despite these efforts, the clinical phenotype appears to extend beyond FTD and ALS into the realm of psychiatric disease, and while highly variable survival rates have been reported, the clinical course of carriers remains relatively unexplored. This report describes two contrasting C9orf72 cases, one with a protracted indolent course dominated by neuropsychiatric features and the other with a rapidly progressive dementia. In both cases, initial structural brain imaging was relatively normal. PMID- 25138489 TI - A critical domain of Sweet potato chlorotic fleck virus nucleotide-binding protein (NaBp) for RNA silencing suppression, nuclear localization and viral pathogenesis. AB - RNA silencing is an important mechanism of antiviral defence in plants. To counteract this resistance mechanism, many viruses have evolved RNA silencing suppressors. In this study, we analysed five proteins encoded by Sweet potato chlorotic fleck virus (SPCFV) for their abilities to suppress RNA silencing using a green fluorescent protein (GFP)-based transient expression assay in Nicotiana benthamiana line 16c plants. Our results showed that a putative nucleotide binding protein (NaBp), but not other proteins encoded by the virus, could efficiently suppress local and systemic RNA silencing induced by either sense or double-stranded RNA (dsRNA) molecules. Deletion mutation analysis of NaBp demonstrated that the basic motif (an arginine-rich region) was critical for its RNA silencing suppression activity. Using confocal laser scanning microscopy imaging of transfected protoplasts expressing NaBp fused to GFP, we showed that NaBp accumulated predominantly in the nucleus. Mutational analysis of NaBp demonstrated that the basic motif represented part of the nuclear localization signal. In addition, we demonstrated that the basic motif in NaBp was a pathogenicity determinant in the Potato virus X (PVX) heterogeneous system. Overall, our results demonstrate that the basic motif of SPCFV NaBp plays a critical role in RNA silencing suppression, nuclear localization and viral pathogenesis. PMID- 25138490 TI - Structural classification and general principles for the design of spherical molecular hosts. AB - Cryptands, carcerands, polyoxometalates, and molecular capsules are cagelike hosts that complex guests through encapsulation. Following the discovery of a nanometer scale supramolecular shell-like spheroid, these and other shell-like hosts were structurally classified. Their frameworks may be catalogued according to principles of solid geometry. This has led to the identification of hosts that have not yet been synthesized or discovered (such as the cuboctahedron shown; X=O, S) and should lead to the design of additional container assemblies. PMID- 25138491 TI - Crystalline bacterial cell surface layers (s layers): from supramolecular cell structure to biomimetics and nanotechnology. AB - An astonishingly broad application potential in biotechnology, biomimetics, and nanotechnology is revealed by studies on the structure, chemistry, biosynthesis, genetics, self-assembly, and function of supramolecular surface layers (S layers). These are monomolecular, crystalline assemblies of protein or glycoprotein subunits and represent one of the most commonly observed surface structures of prokaryotic cell envelopes (see schematic representation of an archaebacterial cell envelope). PMID- 25138492 TI - Miniature continuous-flow polymerase chain reaction: a breakthrough? AB - A time-space conversion enables the polymerase chain reaction (PCR) to be carried out in a continuous-flow process: the mobile reaction mixture is pumped continuously through a glass microchip and passes many times through three constant temperature zones (see picture). The flow rate can be varied to obtain an amplification time of only 90 s. When combined with other continuous-flow microdevices this micromachine may prove useful for routine medical applications and biochemical research. PMID- 25138493 TI - Heterogenization of metallocene catalysts for alkene polymerization. AB - Beyond mere convenience: In large-scale industrial processes for alkene polymerization the essentially homogeneous metallocene/activator catalyst systems are heterogenized (example shown) to improve polymer properties. New mesoporous and organic catalyst supports and their application in this field of catalysis are described. PMID- 25138494 TI - Aromatic polyhedral hydroxyborates: bridging boron oxides and boron hydrides. AB - No explosion, but per-B-hydroxylation occurs if the icosahedral boron hydrides [closo-B12 H12 ](2-) (see picture), [closo-CB11 H12 ](-) , or closo-1,12-(CH2 OH)2 -1,12-C2 B10 H10 are refluxed in 30 % hydrogen peroxide. Thus, the three isoelectronic species [closo-B12 (OH)12 ](2-) , [closo-1-H-1-CB11 (OH)11 ](-) , and closo-1,12-H2 -1,12-C2 B10 (OH)10 were obtained. ?=BH, ?=BOH. PMID- 25138495 TI - The Equilibrium between Localized and Delocalized States of Thermochromic Semibullvalenes and Barbaralanes-Direct Observation of Transition States of Degenerate Cope Rearrangements. AB - The UV/Vis spectra of thermochromic semibullvalenes 1 and barbaralanes recorded at various temperatures yield enthalpy differences between the two degenerate classical structures 1 and 1' and the less stable species (1*) that absorb at long wavelengths. The latter species are interpreted in terms of higher, delocalized states that are located just above the flat potential energy barrier between the ground states (DeltaH(0) =11 (R=H; in butyronitrile), 1 kJ mol(-1) (R=Ph)). PMID- 25138496 TI - Solvent Effects on the Equilibrium between Localized and Delocalized States of Thermochromic Semibullvalenes and Barbaralanes. AB - The position of the equilibrium between localized and delocalized states of thermochromic semibullvalenes and barbaralanes (see the Equation) depends strongly on the solvent. Dipolar aprotic solvents, particularly N,N' dimethylpropylene urea, favor the delocalized, bishomoaromatic state (DeltaH(0) =8 kJ mol(-1) (cyclohexane), DeltaH(0) <0 kJ mol(-1) (N,N'-dimethylpropylene urea)). PMID- 25138497 TI - Efficient cleavage-cross-coupling strategy for solid-phase synthesis-a modular building system for combinatorial chemistry. AB - A new modular building system for the combinatorial chemistry was developed on the basis of triazene linkers. Starting from an aniline system, further functional units and virtually any alkene or alkyne as terminator furnished lipophilic multicomponent systems in high yields and purities without the need for purification steps (see schematic representation). PMID- 25138498 TI - An oxidation-labile traceless linker for solid-phase synthesis. AB - Traceless release of biaryls, acetylenes, alkenes, heterocycles, thioethers, and secondary amines from different solid supports can be achieved under very mild conditions by using a hydrazide group. This group, which is converted into an acyl diazene by oxidation and subsequently cleaved by a nucleophile (see scheme), is thus an attractive new linker for solid-phase synthesis and combinatorial chemistry. PMID- 25138499 TI - Design of new mesogenic block molecules: formation of columnar mesophases by calamitic bolaamphiphiles with lateral lipophilic substituents. AB - Rigid bolaamphiphiles with lateral alkyl chains such as 1 form columnar mesophases of a novel type based on microsegregation of the three incompatible parts of the molecules (shown schematically). PMID- 25138500 TI - Catalytic asymmetric aminohydroxylation with amino-substituted heterocycles as nitrogen sources. AB - The suprafacial, vicinal addition of a heterocyclic moiety and a hydroxyl group is achieved by the osmium-catalyzed asymmetric aminohydroxylation (AA) of olefins with amino-substituted heterocycles as the nitrogen sources. Amino alcohols are obtained in up to 97 % yield and with up to 99 % ee when a ligand derived from dihydroquinidine (DHQD-L) is used [Eq. (1); R(i) indicates the remaining portion of the heterocycle (Het); H2 O is the O source]. The AA can now be considered as a means to directly introduce complex, biologically relevant substructures to hydrocarbon backbones. PMID- 25138501 TI - High-resolution calorimetry: new perspectives for the study of phase transitions. AB - Only 7 pg of substance are needed to measure solid-solid phase transitions in n alkanes with a new type of calorimeter (see schematic picture). This corresponds to a transition heat of only 500 pJ. The small time constant of the calorimeter additionally permits the observation of dynamic effects in the examined phase transitions. PMID- 25138503 TI - Solvothermal Synthesis of the Canted Antiferromagnet {K2 [CoO3 PCH2 N(CH2 CO2 )2 ]}6 ?x H2 O. AB - A rare example of a molecular species prepared by solvothermal synthesis is the macrocyclic cobalt phosphonate/carboxylate 1, whose structure is shown schematically. At low temperatures this compound displays spontaneous magnetization due to canted antiferromagnetic ordering, which is very unusual for a discrete molecular material. PMID- 25138502 TI - Homoleptic lanthanide complexes of chelating phosphanamides-an experimental and theoretical study. AB - Four chelating ligands are present in the first phosphanamide complexes of Group 3 metals and the lanthanides (see structure shown). However, these ligands coordinate to form a distorted molecular structure. The compounds were characterized by single-crystal X-ray structure analysis and quantum-mechanical investigations with density functional theory and MP2 methods. PMID- 25138504 TI - C-C Bond Formation between Fischer Carbene Complexes and Allylic Alcohols by a [3,4] Sigmatropic Rearrangement Promoted by a [1,2] M(CO)5 Shift. AB - A [1,2] M(CO)5 shift promotes a [3,4] sigmatropic rearrangement after the addition of allylic alcohols to Fischer alkenylcarbene complexes of tungsten or chromium in the presence of alkoxide ions. This opens a new synthetic route to the adducts 1. The reaction is also applicable to propargylic alcohols. [M]=Mo(CO)5 , W(CO)5 . PMID- 25138505 TI - Total synthesis of (+)-lactacystin. AB - A double stereodifferentiating crotylation between aldehyde 1 and silane (S)-2 to afford homoallylic alcohol 3 is the key diastereoselective step (anti:syn >30:1) in an efficient asymmetric synthesis of (+)-lactacystin. This compound is a metabolite isolated from Streptomyces sp. OM-6519 that exhibits significant neurotrophic activity. An additional important step in the synthesis is a catalytic asymmetric aminohydroxylation used as the key step in the synthesis of the (2R,3S)-hydroxyleucine synthon. PMID- 25138506 TI - Aerobic Oxidation of Primary Alcohols by a New Mononuclear Cu(II) -Radical Catalyst. AB - Primary alcohols such as ethanol or benzyl alcohol are selectively and catalytically oxidized by the mononuclear copper(II) radical complex 1-a functional model of the metalloenzyme galactose oxidase-with oxygen from air at 20 degrees C to give the corresponding aldehydes and H2 O2 in about 60 % yield. PMID- 25138507 TI - Synthesis, Structure, and Redox Properties of [{(eta(5) -C5 H5 )Co(S2 C6 H4 )}2 Mo(CO)2 ], a Novel Metalladithiolene Cluster. AB - Metal-metal bond formation by a cobaltadithiolene complex was observed for the first time in the reaction of [Co(eta(5) -C5 H5 )(S2 C6 H4 )] with [Mo(CO)3 (py)3 ] and BF3 to give the Co-Mo-Co cluster 1. Cyclic voltammetry reveals that 1 undergoes two one-electron reduction steps at the Co centers, which is indicative of transmission of the Co-Co electronic interaction through the Mo center. PMID- 25138508 TI - The Synthesis and Molecular Structure of the First Two-Coordinate, Dinuclear sigma-Bonded Mercury(I) RHgHgR Compound. AB - A linear Si-Hg-Hg-Si arrangement and a Hg-Hg distance of 265.69 pm are exhibited by the first two-coordinate, dinuclear sigma-bonded organomercury(I) compound 1. It was formed unexpectedly in the reaction of two equivalents of the silane (Me3 SiMe2 Si)3 SiH with tBu2 Hg. In contrast if the reagents are allowed to react in a 1:1 ratio the expected mercury(II) compound (Me3 SiMe2 Si)3 SiHgtBu is obtained. PMID- 25138509 TI - Hexasupersilyl-triprismo-hexastannane (tBu3 Si)6 Sn6 -The First Molecular Tin Compound Containing a Sn6 Prism. AB - Dark violet hexastannane (tBu3 Si)6 Sn6 displays a new framework motif for molecular tin compounds, in which six Sn atoms are located at the corners of a trigonal prism. The compound can be synthesized according to Equation (a). R*=SitBu3 . PMID- 25138510 TI - Syntheses and ligating properties of molybdocene alkoxides-the first heterodimetallic alkoxide containing molybdenum and bismuth. AB - Fluorinated alkoxide ligands RO(-) (R=CH(CF3 )2 ) are the key to the isolation of compounds of the type [Cp2 Mo(OR)2 ]. When electron-donating groups R are employed, the Mo(OR)2 moiety can, and necessarily has to, serve as a ligand for Lewis acidic fragments, allowing the isolation and structural characterization of the first heterodimetallic alkoxide containing a Bi and a Mo center (1). PMID- 25138511 TI - A spreader-bar approach to molecular architecture: formation of stable artificial chemoreceptors. AB - The destructive influence of lateral diffusion on nanostructured monolayers can be prevented by using the spreader-bar technique. This approach allows the formation of stable artificial receptors for barbituric acid by lateral structuring of a dodecanethiol monolayer with molecular spreader-bars from thiobarbituric acid without chemical polymerization (see schematic representation). The new technique may have applications in chemosensors, affinity chromatography, stereoselective catalysis, and molecular electronics. PMID- 25138512 TI - Synthesis and Structures of cis- and trans-[Os(Bcat)(aryl)(CO)2 (PPh3 )2 ]: Compounds of Relevance to the Metal-Catalyzed Hydroboration Reaction and the Metal-Mediated Borylation of Arenes. AB - Support for key steps of the mechanism for the transition metal catalyzed hydroboration reaction is provided by the characterization and reactions of 1, a cis-(boryl)(aryl) complex of osmium(II). This compound readily eliminates o tolylBcat to give the osmium(0) intermediate 2, which in the presence of HBcat reestablishes the osmium-boron bond by forming 3. R=o-tolyl, H2 cat=catechol=1,2 (HO)2 C6 H4 . PMID- 25138513 TI - Thermally Stable Heterobinuclear Bivalent Group 14 Metal Complexes Ar2 M-Sn[1,8 (NR)2 C10 H6 ] (M=Ge, Sn; Ar=2,6-(Me2 N)2 C6 H3 ; R=CH2 tBu). AB - The first thermally robust Ge(II) -Sn(II) compound 1 and the structurally characterized Sn(II) -Sn(II) analogue 2, which maintain their structural integrity in solution, were obtained by treating MAr2 (M=Ge, Sn; Ar=2,6-(Me2 N)2 C6 H3 ) with Sn[1,8-(NR2 )2 C10 H6 ] (R=CH2 tBu). On the basis of structural and spectroscopic data, the M-Sn bond is regarded as the interaction of a MAr2 donor with an Sn[1,8-(NR2 )2 C10 H6 ] acceptor. PMID- 25138514 TI - Kinetic Resolution of Diiron Acyl Complexes-An Approach to Asymmetric Bicyclic beta-Lactams. AB - Kinetic resolution is achieved in the reaction of racemic diiron complexes like 1 with the chiral nitrone (-)-2. Oxidative removal of the metal and reductive cleavage of the N-O bond provides beta-amino acids. This sequence was used in the synthesis of beta-amino acids as well as the corresponding beta-lactams 4 (via 3). PMID- 25138515 TI - Surface coordination chemistry: corrosion inhibition by tetranuclear cluster formation of iron with salicylaldoxime. AB - A tetranuclear iron cluster is the principal component of the purple coatings produced by treating a mild steel surface with a salicylaldoxime corrosion inhibitor. This was shown by comparison of the spectroscopic data with those of the cluster [{Fe(salH)(HsalH)}4 ], which was obtained from FeCl3 and salicylaldoxime (H2 salH) and has a distorted tetrahedral arrangement of Fe(III) atoms coordinated by terminal (1-) and bridging (2-) salicylaldoximate ligands (the central core of the cluster is depicted). PMID- 25138516 TI - Stereoselective Solid-Phase Synthesis of beta-Lactams-A Novel Cyclization/Cleavage Step towards 1-Oxacephams. AB - Despite the antibiotic activity and the attractiveness of beta-lactams, the solid phase synthesis of this class of compounds has been barely reported. Now the diastereoselective synthesis of the 1-oxacepham 2 from the resin-bound beta lactam derivative 1 has been achieved in five steps. The synthesis of 2 and other 1-oxacephams is attractive because all the reaction steps proceed in high yield, the purity of the product is high, and the reaction sequence is simple. PMID- 25138517 TI - A method for the selection of catalytic activity using phage display and proximity coupling. AB - Phage display has been used extensively for the selection of proteins with binding sites for ligands. Here, as illustrated with the example of DNA polymerase, the use of phage display for selection according to catalytic activity is described. Active enzymes are selected by binding of the reaction product P (see the scheme) cross-linked in the proximity of the enzyme E that catalyzed the reaction with the substrate S. PMID- 25138518 TI - Alkyl migration aptitudes in the vinylidene-acetylene rearrangement and isotope effect in the vinylidene formation process from a deuterium-labeled cyclopropene. AB - The secret of the mechanism of vinylidene rearrangements has been unlocked by the use of specifically labeled cyclopropenes under mild thermal conditions (see the Equations). (13) C labeling gives the surprising 1,2-alkyl migratory aptitude sequence Et>iPr>Me. Deuterium labeling yields the first measurement of the primary kinetic isotope effect in the ring opening of a cyclopropene to form a vinylidene. PMID- 25138519 TI - The First Total Synthesis of 6-Sulfo-de-N-acetylsialyl Lewis(x) Ganglioside: A Superior Ligand for Human L-Selectin. AB - Originally discovered as a minor by-product of 6-sulfo-N-acetylsialyl Lewis(x) , the de-N-acetylated form 1 is a superior L-selectin ligand to the N-acetyl form. To substantiate the extraordinary reactivity of 1, it was synthesized for the first time and its binding to L-selectin investigated. Compound 1 and related structures may be high-affinity endogenous ligands for L-selectin that are involved in the interaction of leukocytes with the vascular endothelium. PMID- 25138520 TI - Metabolites with a novel c30 backbone from marine ciliates. AB - Challenging questions are raised about the biosynthetic origin of vannusal A (1), a metabolite that is isolated from the tropical marine ciliate Euplotes vannus and contains an unusual C30 backbone. PMID- 25138521 TI - Molecular Recognition within a Self-Assembled Cylindrical Host. AB - A change in geometry is necessary on entry into the capsule: a supramolecular associate approximately 1.8 nm long (see schematic representation), which consists of two halves stabilized by hydrogen bonds, influences the intra- and intermolecular interactions of the guest molecules encapsulated. Thus tertiary amides and anilides such as 1, which exist in solution preferably as E rotamers, are fixed in the Z conformation inside the capsule for steric reasons. PMID- 25138522 TI - Is the Bis(MU-oxo)dicopper Core Capable of Hydroxylating an Arene? AB - Direct attack of the bis(MU-oxo)dicopper core on an arene appears feasible in tyrosinase and model complexes on the basis of studies of new [Cu(III) 2 (MU-O)2 ](2+) compounds supported by bidentate imine/amine ligands. In the first demonstration of such reactivity for a bis(MU-oxo)dicopper core, decomposition of these intermediates caused hydroxylation of a pendant phenyl ring [Eq. (a)] in a reaction analogous to that catalyzed by tyrosinase. PMID- 25138523 TI - Cyclopropanation enantioselectivity is pressure dependent in supercritical fluoroform. AB - The tunable dielectric constant epsilon of supercritical fluoroform is the explanation for pressure-dependent enantioselectivity in a reaction conducted at low pressure. For the cyclopropanation of styrene and methyl phenyldiazoacetate with a dirhodium catalyst, the enantioselectivity was significantly higher at 52 bar than above 80 bar (see plot). PMID- 25138524 TI - A Diazoalkane Derivative of a Polyoxometalate: Preparation and Structure of [Mo6 O18 (NNC(C6 H4 OCH3 )CH3 )](2-). AB - A new metathetical route to diazoalkane complexes is described which allows the introduction of such ligands into previously inaccessible environments. The method, which involves the exchange of oxo and [N2 CR2 ] ligands, is illustrated by the preparation of the first diazoalkane-polyoxometalate complex 1. PMID- 25138525 TI - Heterosupramolecular chemistry: programmed pseudorotaxane assembly at the surface of a nanocrystal. AB - Gold nanocrystals, stabilized by thiols covalently bound to a dibenzo[24]crown-8 moiety, have been programmed to recognize and selectively bind dibenzylammonium cations in solution. This results in a self-organization process at the surface of a nanocrystal with the assembly of a pseudorotaxane (see picture). PMID- 25138526 TI - Structural abnormalities of corpus callosum and cortical axonal tracts accompanied by decreased anxiety-like behavior and lowered sociability in spock3- mutant mice. AB - Spock3/Testican-3 is a nervous system-expressed heparan sulfate proteoglycan belonging to a subgroup of the BM-40/SPARC/osteonectin family, the role of which in brain development is unclear. Because Spock1, a member of the Spock family, inhibits their attachment to substrates and the neurite outgrowth of cultured neuronal cells, Spock3 is also thought to be similarly involved in the neuronal development. In the present study, we established a Spock3-mutant mouse harboring a deletion extending from the presumptive upstream regulatory region to exon 4 of the Spock3 locus and performed histological and behavioral studies on these mutant mice. In wild-type (WT) mice, all Spock members were clearly expressed during brain development. In adults, intense Spock1 and Spock2 expressions were observed throughout the entire brain; whereas, Spock3 expression was no longer visible except in the thalamic nuclei. Thus, Spock3 expression is mostly confined to the developmental stage of the brain. In adult mutant mice, the cells of all cortical layers were swollen. The corpus callosum was narrowed around the central region along the rostral-caudal axis and many small spaces were observed without myelin sheaths throughout the entire corpus callosum. In addition, the cortical input and output fibers did not form into thick bundled fibers as well as the WT counterparts did. Moreover, a subpopulation of corticospinal axonal fibers penetrated into the dorsal striatum with moderately altered orientations. Consistent with these modifications of brain structures, the mutant mice exhibited decreased anxiety-like behavior and lowered sociability. Together, these results demonstrate that Spock3 plays an important role in the formation or maintenance of major neuronal structures in the brain. PMID- 25138527 TI - Global disulfide bond profiling for crude snake venom using dimethyl labeling coupled with mass spectrometry and RADAR algorithm. AB - Snake venom consists of toxin proteins with multiple disulfide linkages to generate unique structures and biological functions. Determination of these cysteine connections usually requires the purification of each protein followed by structural analysis. In this study, dimethyl labeling coupled with LC-MS/MS and RADAR algorithm was developed to identify the disulfide bonds in crude snake venom. Without any protein separation, the disulfide linkages of several cytotoxins and PLA2 could be solved, including more than 20 disulfide bonds. The results show that this method is capable of analyzing protein mixture. In addition, the approach was also used to compare native cytotoxin 3 (CTX III) and its scrambled isomer, another category of protein mixture, for unknown disulfide bonds. Two disulfide-linked peptides were observed in the native CTX III, and 10 in its scrambled form, X-CTX III. This is the first study that reports a platform for the global cysteine connection analysis on a protein mixture. The proposed method is simple and automatic, offering an efficient tool for structural and functional studies of venom proteins. PMID- 25138528 TI - Developmental trajectories of prejudice and tolerance toward immigrants from early to late adolescence. AB - Adolescence is an important period for the development of relationships between immigrants and non-immigrants, yet little is known about how problematic personality traits affect adolescents' relationships with and attitudes toward immigrants. This work identified the roles of intergroup relationships and one dimension of problematic personality traits, namely callous-unemotional traits, in the development of adolescents' tolerance and prejudice. Three annual measurements of a large community sample (N = 1,542) of non-immigrant adolescents (M age = 15.31 at first measurement; 50.2% girls) were used to show that tolerance and prejudice toward immigrants represent two dimensions with distinct developmental trajectories from early to late adolescence. Callous-unemotional traits predicted fewer decreases in prejudice toward immigrants, yet were not directly associated with tolerance. Intergroup friendships predicted stronger increases in tolerance, which, in turn, predicted decreases in prejudice toward immigrants. Thus, tolerance and prejudice toward immigrants seem to be differentially influenced by social experiences and problematic personality traits. PMID- 25138530 TI - Scenario planning for community development in Vietnam: a new tool for integrated health approaches? AB - BACKGROUND: Like many countries in Southeast Asia, Vietnam's rapid population and economic growth has met challenges in infrastructure development, especially sanitation in rural areas. OBJECTIVE: As an entry point, we developed scenario planning as an action-research tool in a peri-urban community to identify first steps towards improving their complex sanitation problem and to, systemically, address emerging/re-emerging infectious diseases, as these are commonly linked to unsafe water and inadequate sanitation conditions. As an integrated approach, the process of constructing scenarios allowed us to work across sectors and stakeholders to incorporate this knowledge into a common vision. DESIGN: We conducted focus group discussions to identify and rank driving forces, orally constructed scenarios for the most uncertain drivers, discussed scenario implications and options, and examined the overall process for usefulness and sustainability. During a one-month scoping phase and in between focus group meetings, we carried out household visits which helped us understand the context of data and gather feedback from participants outside of the formal data collection process. Recorded results from these activities were used to develop subsequent tools. RESULTS AND CONCLUSIONS: The research process gave us insights into how to adapt the scenario planning tool to identify alternative options. This involved choosing boundary partners, negotiating priorities, drawing out participant learning through self-assessment of our process (a prerequisite for changing mental models and thus achieving outcomes), and understanding how conveyed messages may reinforce the status quo. These insights showed the importance of examining research results beyond outputs and outcomes, namely through process. PMID- 25138529 TI - Effects of advanced glycation end products on calcium handling in cardiomyocytes. AB - BACKGROUND AND AIMS: Advanced glycation end products (AGEs) accumulate in diabetes and the engagement of receptor for AGE (RAGE) by AGEs contributes to the pathogenesis of diabetic cardiomyopathy. This study aims to investigate the effects of AGE/RAGE on ryanodine receptor (RyR) activity and Ca(2+) handling in cardiomyocytes to elucidate the possible mechanism underlying cardiac dysfunction in diabetic cardiomypathy. METHODS AND RESULTS: Confocal imaging Ca(2+) spark, the elementary Ca(2+) release event reflecting RyR activity in intact cell, as well as SR Ca(2+) content and systolic Ca(2+) transient were performed in cultured neonatal rat ventricular myocytes. The results show that 50 mg/ml AGE increased the frequency of Ca(2+) sparks by 160%, while 150 mg/ml AGE increased it by 53%. AGE decreased the amplitude, width and duration of Ca(2+) sparks. Blocking RAGE with anti-RAGE IgG completely abolished the alteration of Ca(2+) sparks. The SR Ca(2+) content indicated by the amplitude (DeltaF/F0) of 20 mM caffeine-elicited Ca(2+) transient was significantly decreased by 150 mg/ml AGE. In parallel, the amplitude of systolic Ca(2+) transient evoked by 1 Hz-field stimulation was remarkably decreased by 150 mg/ml AGE. The anti-RAGE antibody completely restored the impaired SR load and systolic Ca(2+) transient. CONCLUSION: AGE/RAGE signal enhanced Ca(2+) spark-mediated SR Ca(2+) leak, causing partial depletion of SR Ca(2+) content and consequently decreasing systolic Ca(2+) transient, which may contribute to contractile dysfunction in diabetic cardiomyopathy. PMID- 25138531 TI - Experiences in anti-tuberculosis treatment in patients with multiple previous treatments and its impact on drug resistant tuberculosis epidemics. AB - BACKGROUND: Tuberculosis (TB) patients with a history of multiple anti-TB treatments are the 'neglected' group to the free anti-TB treatment policy in China. OBJECTIVE: To understand the experiences of TB patients with multiple previous treatments with regard to bacteriological diagnosis and treatment regimens, especially for second-line anti-TB drugs, and how this might influence the risks of multidrug and extensively drug-resistant TB (M/XDR-TB). DESIGN: A cross-sectional study was conducted in 10 county/district TB clinics in five provinces of China. The study participants were TB patients that had at least two previous treatment episodes that lasted longer than 1 month each. Face-to-face interviews and drug susceptibility testing (DST) were conducted with the consenting participants. RESULTS: A total of 328 TB patients were recruited. The proportion of multidrug-resistant tuberculosis (MDR-TB) was 58.2% in the 287 DST confirmed patients. Forty-two percent of the patients did not complete their first treatment course. About 23.8% of the participants had a history of taking second-line drugs, and more than 77.8% of them were treated in county TB dispensaries where only sputum microscopy was applied. Multivariate analysis found that the use of second-line drugs was significantly associated with frequency of previous treatments (p<0.01), but not with drug resistance profiles of patients. CONCLUSIONS: Patients with multiple previous treatments are at extremely high risk of MDR-TB in China. The unregulated use of second-line drugs bring about the threat of XDR-TB epidemic. DST-guided treatment and strict regulations of anti-TB treatment should be assured for the high-risk TB patients for the prevention and control of M/XDR-TB. PMID- 25138532 TI - Interpretive focus groups: a participatory method for interpreting and extending secondary analysis of qualitative data. AB - BACKGROUND: Participatory approaches to qualitative research practice constantly change in response to evolving research environments. Researchers are increasingly encouraged to undertake secondary analysis of qualitative data, despite epistemological and ethical challenges. Interpretive focus groups can be described as a more participative method for groups to analyse qualitative data. OBJECTIVE: To facilitate interpretive focus groups with women in Papua New Guinea to extend analysis of existing qualitative data and co-create new primary data. The purpose of this was to inform a transformational grounded theory and subsequent health promoting action. DESIGN: A two-step approach was used in a grounded theory study about how women experience male circumcision in Papua New Guinea. Participants analysed portions or 'chunks' of existing qualitative data in story circles and built upon this analysis by using the visual research method of storyboarding. RESULTS: New understandings of the data were evoked when women in interpretive focus groups analysed the data 'chunks'. Interpretive focus groups encouraged women to share their personal experiences about male circumcision. The visual method of storyboarding enabled women to draw pictures to represent their experiences. This provided an additional focus for whole-of group discussions about the research topic. CONCLUSIONS: Interpretive focus groups offer opportunity to enhance trustworthiness of findings when researchers undertake secondary analysis of qualitative data. The co-analysis of existing data and co-generation of new data between research participants and researchers informed an emergent transformational grounded theory and subsequent health promoting action. PMID- 25138533 TI - Paracelsus in nanotoxicology. PMID- 25138535 TI - Ubiquitin-activating enzyme is necessary for 17beta-estradiol-induced breast cancer cell proliferation and migration. AB - The sex steroid hormone 17beta-estradiol (E2) regulates breast cancer (BC) cell proliferation and migration through the activation of a plethora of signal transduction cascades (e.g., PI3K/AKT activation) starting after E2 binding to the estrogen receptor alpha (ERalpha). The activity of the ubiquitin (Ub)-system modulates many physiological processes (e.g., cell proliferation and migration), and recently, a specific inhibitor (Pyr-41) of the Ub-activating enzyme (E1), which works as the activator of the Ub-based signaling, has been identified to prevent the functions of the Ub-system. Here, by using Pyr-41, we studied the involvement of the Ub-system in E2-induced signaling to proliferation and migration of BC cells. Our data indicate that E1 activity is involved in the E2:ERalpha signaling important for cell proliferation and migration through the modulation of the E2-evoked activation of the PI3K/AKT and the p38/MAPK pathways. These discoveries indicate a new molecular circuitry that can be further explored to define new opportunities for BC treatment. PMID- 25138537 TI - Changes in sexual signals are greater than changes in ecological traits in a dichromatic group of fishes. AB - Understanding the mechanisms by which phenotypic divergence occurs is central to speciation research. These mechanisms can be revealed by measuring differences in traits that are subject to different selection pressures; greater influence of different types of selection can be inferred from greater divergence in associated traits. Here, we address the potential roles of natural and sexual selection in promoting phenotypic divergence between species of snubnose darters by comparing differences in body shape, an ecologically relevant trait, and male color, a sexual signal. Body shape was measured using geometric morphometrics, and male color was measured using digital photography and visual system-dependent color values. Differences in male color are larger than differences in body shape across eight allopatric, phylogenetically independent species pairs. While this does not exclude the action of divergent natural selection, our results suggest a relatively more important role for sexual selection in promoting recent divergence in darters. Variation in the relative differences between male color and body shape across species pairs reflects the continuous nature of speciation mechanisms, ranging from ecological speciation to speciation by sexual selection alone. PMID- 25138536 TI - The provision of mental health treatment after screening: exploring the relationship between treatment setting and treatment intensity. AB - OBJECTIVE: Primary care screening programs for mental health disorders are designed to detect patients who might benefit from treatment. As such, the utility of these programs is predicated on the actions that take place in response to a positive screen. Our objective was to characterize the cascade of care delivery steps following a positive screen for a mental health disorder. METHOD: We examined the care received by primary care patients over the year following a new positive screen for depression, posttraumatic stress disorder (PTSD) or alcohol misuse. We characterized whether the care adhered to practice guidelines for related mental health disorders and whether involvement of mental health specialists led to higher use of guideline-adherent practices. RESULTS: Many patients received appropriate treatment in the primary care setting and those whose scores were consistent with more severe illness were more likely to receive care in a mental health setting. Patients with positive screens for depression and PTSD who went on to be seen in mental health clinics received care that was consistent with treatment guidelines for the related disorder most of the time. In the case of patients with positive screens for alcohol misuse, few received guideline-recommended medications in any setting. However, a substantial portion of patients received some alcohol-related counseling from their primary care physicians during the visit in which their alcohol misuse was detected. CONCLUSION: It appears that the treatment system for mental health problems, which extends from primary care settings to mental health subspecialty settings, can provide adequate care when patients' mental health problems are identified through screening. The care provided in all settings can be improved, and additional steps to enhance the quality of care are warranted. This should include additional efforts to align screening and treatment. PMID- 25138538 TI - Single-stage multiple-tract percutaneous nephrolithotomy in the treatment of staghorn stones under total ultrasonography guidance. AB - OBJECTIVE: To evaluate the safety and efficacy of single-stage multiple-tract percutaneous nephrolithotomy (PCNL) in the treatment of staghorn stones solely guided by ultrasonography (US). PATIENTS AND METHODS: From May 2007 to July 2012, 55 single-stage multiple-tract PCNL procedures were performed (53 patients, of whom 2 had bilateral stones). Caliceal puncture and dilatation were performed under US guidance in all cases. The procedure was evaluated for access success, length of postoperative hospital stay, complications (modified Clavien system), and stone clearance. RESULTS: The mean (+/-SD) operating time was 84.87 +/- 24.9 min, with a mean (+/-SD) postoperative hospital stay of 5.2 +/- 1.31 days. The patients experienced a mean (+/-SD) decrease in hemoglobin level of 8.23 +/- 2.39 g/l and the stone-free rate after single-stage surgery was 78.18%. Extracorporeal shock wave lithotripsy was indicated in 2 cases as an auxiliary treatment. There were 10 grade 1 (62.5%) and 6 grade 2 (37.5%) complications; however, there were no complications above grade 3. CONCLUSION: Total US-guided single-stage multiple tract PCNL for treating staghorn calculi in selected cases is safe, feasible, and may be performed with an acceptable morbidity and with the advantage of preventing radiation hazards and damage to adjacent organs. PMID- 25138539 TI - Dextrin/poly (HEMA): pH responsive porous hydrogel for controlled release of ciprofloxacin. AB - Herein, we report an oral route administration for ciprofloxacin hydrochloride delivery using dextrin and poly (2-hydroxyethyl methylacrylate) based crosslinked hydrogel (c-Dxt/pHEMA). Various characteristics such as FTIR spectra, XRD analyses, UV-VIS-NIR spectra, FESEM and E-SEM analyses, rheological characteristics, gel kinetics, deswelling characteristics as well as biodegradation study of the hydrogel have been carried out. FTIR, XRD along with solid state UV-VIS-NIR analyses explain the good compatibility between the drug and the hydrogel matrix. The in vitro release study demonstrates that c-Dxt/pHEMA releases ciprofloxacin in a sustained way (33.75% of drug has been released in 18h) and is expected to be a promising matrix for ciprofloxacin carrier. The release kinetics and mechanism suggest that drug release follows first order kinetics and non-Fickian diffusion mechanism. Finally, the hydrogel shows excellent physical stability as carrier for ciprofloxacin up to 3 months. PMID- 25138534 TI - Loss of PiT-1 results in abnormal endocytosis in the yolk sac visceral endoderm. AB - PiT-1 protein is a transmembrane sodium-dependent phosphate (Pi) transporter. PiT 1 knock out (KO) embryos die from largely unknown causes by embryonic day (E) 12.5. We tested the hypothesis that PiT-1 is required for endocytosis in the embryonic yolk sac (YS) visceral endoderm (VE). Here we present data supporting that PiT-1 KO results in a YS remodeling defect and decreased endocytosis in the YS VE. The remodeling defect is not due to an upstream cardiomyocyte requirement for PiT-1, as SM22alphaCre-specific KO of PiT-1 in the developing heart and the YS mesodermal layer (ME) does not recapitulate the PiT-1 global KO phenotype. Furthermore, we find that high levels of PiT-1 protein localize to the YS VE apical membrane. Together these data support that PiT-1 is likely required in YS VE. During normal development maternal immunoglobulin (IgG) is endocytosed into YS VE and accumulates in the apical side of the VE in a specialized lysosome termed the apical vacuole (AV). We have identified a reduction in PiT-1 KO VE cell height and a striking loss of IgG accumulation in the PiT-1 KO VE. The endocytosis genes Tfeb, Lamtor2 and Snx2 are increased at the RNA level. Lysotracker Red staining reveals a loss of distinct AVs, and yolk sacs incubated ex vivo with phRODO Green Dextran for Endocytosis demonstrate a functional loss of endocytosis. As yolk sac endocytosis is controlled in part by microautophagy, but expression of LC3 had not been examined, we investigated LC3 expression during yolk sac development and found stage-specific LC3 RNA expression that is predominantly from the YS VE layer at E9.5. Normalized LC3-II protein levels are decreased in the PiT-1 KO YS, supporting a requirement for PiT-1 in autophagy in the YS. Therefore, we propose the novel idea that PiT-1 is central to the regulation of endocytosis and autophagy in the YS VE. PMID- 25138540 TI - Adsorption of copper(II) ions by a chitosan-oxalate complex biosorbent. AB - Oxalic acid, an effective metal-chelating ligand, is abundant in natural resources. In this study, a chitosan-oxalate complex biosorbent (COCB) was prepared by an iontropic cross-linking method. The COCB beads were characterized by Fourier transform infrared (FT-IR) spectra, X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The XRD analysis shows that Cu(II) ions can form complexes with chitosan and oxalate. Adsorption of Cu(II) ions onto COCB beads was pH-dependent. The isothermal adsorption data fitted well to Langmuir equation with the maximum adsorption capacities of 227.27 mg/g for porous COCB beads and 175.44 mg/g for non-porous COCB beads at pH 5.0. The adsorption kinetics described by the pseudo-second-order diffusion models, suggesting that the rate-limiting step in adsorption was chemical sorption. Thermodynamic parameters (DeltaG degrees <0 and DeltaH degrees >0) indicated a spontaneous and endothermic adsorption process. The COCB bioadsorbent exhibited fast adsorption rate and high adsorption capacity for Cu(II) uptake. PMID- 25138541 TI - Solvent effects on polymer sorting of carbon nanotubes with applications in printed electronics. AB - Regioregular poly(3-alkylthiophene) (P3AT) polymers have been previously reported for the selective, high-yield dispersion of semiconducting single-walled carbon nanotubes (SWCNTs) in toluene. Here, five alternative solvents are investigated, namely, tetrahydrofuran, decalin, tetralin, m-xylene, and o-xylene, for the dispersion of SWCNTs by poly(3-dodecylthiophene) P3DDT. The dispersion yield could be increased to over 40% using decalin or o-xylene as the solvents while maintaining high selectivity towards semiconducting SWCNTs. Molecular dynamics (MD) simulations in explicit solvents are used to explain the improved sorting yield. In addition, a general mechanism is proposed to explain the selective dispersion of semiconducting SWCNTs by conjugated polymers. The possibility to perform selective sorting of semiconducting SWCNTs using various solvents provides a greater diversity of semiconducting SWCNT ink properties, such as boiling point, viscosity, and surface tension as well as toxicity. The efficacy of these new semiconducting SWCNT inks is demonstrated by using the high boiling point and high viscosity solvent tetralin for inkjet-printed transistors, where solvent properties are more compatible with the inkjet printing head and improved droplet formation. PMID- 25138542 TI - Bone augmentation using a synthetic hydroxyapatite/silica oxide-based and a xenogenic hydroxyapatite-based bone substitute materials with and without recombinant human bone morphogenetic protein-2. AB - AIM: To test whether or not bone regeneration using deproteinized bovine bone mineral (DBBM) is comparable to hydroxyapatite/silica oxide (HA/SiO) and to test the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) as an adjunct to DBBM for localized bone regeneration. MATERIALS AND METHODS: In each of the 10 rabbits, 4 titanium cylinders were placed on the external cortical plates of their calvaria. Four treatment modalities were randomly allocated: (i) empty, (ii) HA/SiO, (iii) DBBM, and (iv) DBBM plus rhBMP-2 (DBBM/BMP). The animals were sacrificed at week 8. Descriptive histology and histomorphometric assessment using a superimposed test grid of points and cycloids were performed. RESULTS: The mean number of points of the test grid coinciding with bone within the cylinder reached 124 +/- 35 bone points for empty controls, 92 +/- 40 bone points for DBBM, 98 +/- 44 bone points for synthetic HA/SiO, and 146 +/- 34 bone points DBBM/BMP. The P-value for DBBM with and without BMP reached a borderline statistical significance of 0.051. However, the area of bone regeneration within the cylinders peaked for DBBM/BMP and was statistically significantly higher compared with empty cylinders (P < 0.05). The bone-to-bone substitute contact ranged between 32.9% +/- 21.7 for DBBM, 39.6 +/- 18.4% for HA/SiO, and 57.8% +/- 10.2 for DBBM/BMP. The differences between DBBM/BMP and controls (DBBM, HA/SiO) were statistically significant (P < 0.05). CONCLUSIONS: DBBM and HA/SiO rendered comparable amounts of bone regeneration. The addition of rhBMP-2 to DBBM resulted in more favorable outcomes with respect to the area of bone regeneration and to bone-to-implant contact, thereby indicating the potential of this growth factor to enhance bone regeneration within this animal model. PMID- 25138543 TI - Successful peripheral neuromodulation for phantom limb pain. AB - SETTING: For decades, the heterogeneity of the amputee population and the complex interaction of biopsychosocial factors have confounded researchers' attempts to develop an effective treatment for phantom limb pain. Therefore, it remains difficult to treat, and affected patients often experience decreased quality of life, increased psychological distress, and poorer health outcomes. PATIENT: In the case study, we report a novel strategy for the peripheral placement of neuromodulation leads for the treatment of phantom limb pain in a patient who subsequently described complete and consistent pain relief independent of significant variations in psychosocial stress. PMID- 25138544 TI - Injury Response of Resected Human Brain Tissue In Vitro. AB - Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by resection (interruption of the circulation) and aggravated by the preparation of slices (severed neuronal and glial processes and blood vessels) reflect the reaction of human brain tissue to severe injury. We investigated this process using immunocytochemical markers, reverse transcriptase quantitative polymerase chain reaction and Western blot analysis. Essential features were rapid shrinkage of neurons, loss of neuronal marker expression and proliferation of reactive cells that expressed Nestin and Vimentin. Also, microglia generally responded strongly, whereas the response of glial fibrillary acidic protein-positive astrocytes appeared to be more variable. Importantly, some reactive cells also expressed both microglia and astrocytic markers, thus confounding their origin. Comparison with post-mortem human brain tissue obtained at rapid autopsies suggested that the reactive process is not a consequence of epilepsy. PMID- 25138545 TI - Characterization of adipose-derived stem cells of anatomical region from mice. AB - BACKGROUND: Stem cells constitute a group of great capacity for self-renewal, long-term viability, and multi-lineage potential. Several studies have provided evidence that adipose tissue represents an alternative source of stem cells, with the main benefit of adipose-derived stem cells being that they can be easily harvested from patients by a simple minimally invasive method and can be easily cultured. The aim of this study was to establish a culture protocol for obtaining and characterizing adipose-derived stem cells (ADSCs) from C57BL/6 J mice. RESULTS: The results showed that the yield, viability, and cell morphology obtained differ according to the age of isolated anatomic regions of the adipose tissue from ovarian and epididymis. The results of determination of cyclin D1 showed uniformity in the expression between different populations of ADSCs. A significant increase in the expression of caspase-3 active, was also observed in large cell populations from mice after 120 days. ADSCs were positive for mesenchymal markers CD90 and CD105, Nanog, SSEA-1, CD106, and VEGFR-1, and negative for hematopoietic markers CD34 and CD45. A large number of cells in S + G2/M phases was also observed for both sexes, demonstrating high proliferative capacity of ADSCs. CONCLUSIONS: We observed that the adipose tissue of C57BL/6 J mice, isolated from the studied anatomic regions, is a promising source for obtaining pluripotent mesenchymal stem cells with high viability and proliferative response. PMID- 25138546 TI - Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation. AB - The aim of this study is to use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. Patients treated with (n = 28) or without chemotherapy (n = 37) and healthy controls (n = 32) were scanned coincident with pre- and one month post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response, characterized by higher spatial variance in executive network activity, than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction. PMID- 25138547 TI - Effects of radioiodine treatment for differentiated thyroid cancer on testis function. AB - OBJECTIVE: To evaluate the effects of radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) on testis function. DESIGN: A prospective longitudinal single-centre study was performed. A comprehensive andrological evaluation including hormonal assessment, semen analysis and scrotal ultrasound was undertaken in male patients undergoing RAI treatment for DTC. METHODS: Hormonal assessment of FSH, LH, testosterone (T), sperm concentration and motility and testis volume were determined in 20 patients in basal conditions, 6 and 12 months after RAI. Results were analysed in the whole group of patients and then separately in those who received one single ablative treatment ('Single' group, n = 10) and those who received multiple treatments ('Multiple' group, n = 10). RESULTS: In basal conditions, 3 of 20 (15%) patients had a reduced sperm count and belonged to the 'Multiple' group. After RAI, an increase of FSH (8.8 +/ 1.2 UI/l vs 5.2 +/- 1.2, P < 0.005) and a decrease in sperm concentration (28.8 +/- 7.7 millions/ml vs 54.5 +/- 7.1, P < 0.005) and testis volume (15.2 +/- 3.1 vs 13.7 +/- 0.8 ml, P < 0.005) occurred at 6 months in the whole group. One year after RAI, seven patients had oligozoospermia (five from the 'Multiple' group and two from the 'Single' group). Permanent impairment of one or more testis function parameters was observed in patients who underwent multiple RAI treatments: 50% for sperm count, 40% for FSH levels and testis volume and, respectively, in 20 and 10% of those who received one single RAI treatment. CONCLUSIONS: The single ablative RAI treatment in cancer patients is better tolerated respect multiple RAI treatments regard testis function. Multiple treatments for recurrent or metastatic disease may cause a permanent impairment of one or more parameters related to the reproductive potential of male patients. PMID- 25138548 TI - Irreversible airway obstruction assessed by high-resolution computed tomography (HRCT), exhaled nitric oxide (FENO), and biological markers in induced sputum in patients with asthma. AB - OBJECTIVE: The objective of this study was to explore the significance of assessing irreversible airway obstruction (IAO) in asthma patients by high resolution computed tomography (HRCT), biological markers in induced sputum, and exhaled nitric oxide (FENO). METHODS: The study was conducted in 34 patients with IAO, 46 patients with reversible airway obstruction (RAO), 40 patients who did not have airway obstruction (NAO), and 40 healthy subjects serving as controls. These patients received a step therapy for at least 3 months based on the guidelines for the prevention and treatment of asthma. After achieving complete or partial control of asthma, HRCT, lung function, FENO, and chemokine levels in induced sputum were measured. RESULTS: The airway wall area (WA; %) correlated with forced expiratory volume-1 (FEV-1(L); r = -0.67, p < 0.0001), and significant differences in bronchial wall thickening (BWT) of the LEVEL E generation airways were observed between the asthma and control groups (p < 0.01). FENO levels correlated with FEV-1 (%) in the IAO group (r = 0.49, p = 0.01). The levels of matrix metalloproteases-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in asthma patients with IAO, RAO, and NAO were significantly higher than those in the controls (p < 0.05). The level of neutrophilia in the sputum from the IAO group was higher than that from the RAO, NAO and control groups. CONCLUSION: Asthma patients with IAO have an increased BWT. Airway measurements with HRCT scans appear to be valuable in the evaluation of airway remodeling in asthma patients with IAO. PMID- 25138549 TI - Dabigatran: patient management in specific clinical settings. AB - Dabigatran, a direct thrombin inhibitor, is licensed for the prevention of venous thromboembolism after knee and hip replacement, the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for the treatment of acute venous thromboembolism. As dabigatran has a favourable benefit risk profile, it is being increasingly used. Dabigatran differs from vitamin K antagonists as regards its pharmacological characteristics and its impact on certain laboratory tests, and also in the lack of a direct antagonist that can reverse dabigatran-induced anticoagulation. In emergency settings such as acute bleeding, emergency surgery, acute coronary syndrome, thrombolysis for ischaemic stroke or overdosing, specific strategies are required. A working group of experts from various disciplines has developed strategies for the management of dabigatran-treated patients in emergency settings. PMID- 25138551 TI - Skeletal (stromal) stem cells: an update on intracellular signaling pathways controlling osteoblast differentiation. AB - Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy for identifying druggable targets for enhancing bone formation. This review will discuss the functions and the molecular mechanisms of action on osteoblast differentiation and bone formation; of a number of recently identified regulatory molecules: the non canonical Notch signaling molecule Delta-like 1/preadipocyte factor 1 (Dlk1/Pref 1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone. PMID- 25138550 TI - MicroRNA-17/20a inhibits glucocorticoid-induced osteoclast differentiation and function through targeting RANKL expression in osteoblast cells. AB - Glucocorticoids act on the osteoblasts to up-regulate the expression of RANKL, which is very important in the etiology of glucocorticoid-induced osteoclast differentiation and bone resorption. The mechanisms of this process are still not completely understood. Recent studies have shown that glucocorticoids mediate osteoblast function by decreasing the expression of microRNA-17-92a cluster. Coincidentally, we found that the microRNA-17/20a (microRNA-17, microRNA-20a) seed sequences were also complementary to a sequence conserved in the 3'- untranslated region of RANKL mRNA. Therefore, we hypothesized that glucocorticoids might promote osteoblast-derived RANKL expression by down regulating microRNA-17/20a, which favors differentiation and function of the osteoclasts. In the present study, Western blot analysis showed that microRNA 17/20a markedly lowered the levels of RANKL protein and attenuated dexamethasone induced RANKL expression in the osteoblasts. The post-transcriptional repression of RANKL by microRNA-17/20a was further confirmed by the luciferase reporter assay. Furthermore, we found that dexamethasone-induced osteoclast differentiation and function were significantly attenuated in co-culture with osteoblast over-expressed microRNA-17/20a and osteoclast progenitors. These results showed that microRNA-17/20a may play a significant role in glucocorticoid induced osteoclast differentiation and function by targeting the RANKL expression in osteoblast cells. PMID- 25138552 TI - Mathematical modelling and optimization of synthetic textile dye removal using soil composites as highly competent liner material. AB - Soil is widely used as adsorbent for removing toxic pollutants from their aqueous solutions due to its wide availability and cost efficiency. This study investigates the potential of soil and soil composites for removal of crystal violet (CV) dye from solution on a comparative scale. Optimisation of different process parameters was carried out using a novel approach of response surface methodology (RSM) and a central composite design (CCD) was used for determining the optimum experimental conditions, as well as the result of their interactions. Around 99.85 % removal of CV was obtained at initial pH 6.4, which further increased to 99.98 % on using soil and cement composite proving it to be the best admixture of those selected. The phenomenon was found to be represented best by the Langmuir isotherm at different temperatures. The process followed the pseudo second-order kinetic model and was determined to be spontaneous chemisorption in nature. This adsorbent can hence be suggested as an appropriate liner material for the removal of CV dye. PMID- 25138553 TI - Spatial distribution of heavy metal contamination in soils near a primitive e waste recycling site. AB - The total concentrations of 12 heavy metals in surface soils (SS, 0-20 cm), middle soils (MS, 30-50 cm) and deep soils (DS, 60-80 cm) from an acid-leaching area, a deserted paddy field and a deserted area of Guiyu were measured. The results showed that the acid-leaching area was heavily contaminated with heavy metals, especially in SS. The mean concentrations of Ni, Cu, Zn, Cd, Sn, Sb and Pb in SS from the acid-leaching area were 278.4, 684.1, 572.8, 1.36, 3,472, 1,706 and 222.8 mg/kg, respectively. Heavy metal pollution in the deserted paddy field was mainly concentrated in SS and MS. The average values of Sb in SS and MS from the deserted paddy field were 16.3 and 20.2 mg/kg, respectively. However, heavy metal contamination of the deserted area was principally found in the DS. Extremely high concentrations of heavy metals were also observed at some special research sites, further confirming that the level of heavy metal pollution was very serious. The geoaccumulation index (Igeo) values revealed that the acid leaching area was severely polluted with heavy metals in the order of Sb > Sn > Cu > Cd > Ni > Zn > Pb, while deserted paddy field was contaminated predominately by metals in the order of Sb > Sn > Cu. It was obvious that the concentrations of some uncommon contaminants, such as Sb and Sn, were higher than principal contaminants, such as Ni, Cu, Zn and Pb, suggesting that particular attention should be directed to Sn and Sb contamination in the future research of heavy metals in soils from e-waste-processing areas. Correlation analysis suggested that Li and Be in soils from the acid-leaching area and its surrounding environment might have originated from other industrial activities and from batteries, whereas Ni, Cu, Zn, Cd, Pb, Sn and Sb contamination was most likely caused by uncontrolled electronic waste (e-waste) processing. These results indicate the significant need for optimisation of e-waste-dismantling technologies and remediation of polluted soil environment. PMID- 25138554 TI - Hydroxyl radical reaction rate coefficients as a function of temperature and IR absorption cross sections for CF3CH=CH2 (HFO-1243zf), potential replacement of CF3CH2F (HFC-134a). AB - CF3CH=CH2 (hydrofluoroolefin, HFO-1243zf) is a potential replacement of high global-warming potential (GWP) hydrofluorocarbon (HFC-134a, CF3CFH2). Both the atmospheric lifetime and the radiative efficiency of HFO-1243zf are parameters needed for estimating the GWP of this species. Therefore, the aim of this work is (i) to estimate the atmospheric lifetime of HFO-1243zf from the reported OH rate coefficients, k OH, determined under tropospheric conditions and (ii) to calculate its radiative efficiency from the reported IR absorption cross sections. The OH rate coefficient at 298 K also allows the estimation of the photochemical ozone creation potential (epsilon(POCP)). The pulsed laser photolysis coupled to a laser-induced fluorescence technique was used to determine k OH for the reaction of OH radicals with HFO-1243zf as a function of pressure (50-650 Torr of He) and temperature (263-358 K). Gas-phase IR spectra of HFO-1243zf were recorded at room temperature using a Fourier transform IR spectrometer between 500 and 4,000 cm(-1). At all temperatures, k OH did not depend on bath gas concentration (i.e., on the total pressure between 50 and 650 Torr of He). A slight but noticeable T dependence of k OH was observed in the temperature range investigated. The observed behavior is well described by the following Arrhenius expression: k OH(T) = (7.65 +/- 0.26) * 10(-13) exp [(165 +/- 10) / T] cm(3) molecule(-1) s(-1). Negligible IR absorption of HFO-1243zf was observed at wavenumbers greater than 1,700 cm(-1). Therefore, IR absorption cross sections, [Formula: see text], were determined in the 500-1,700 cm(-1) range. Integrated [Formula: see text] were determined between 650 and 1,800 cm(-1) for comparison purposes. The main diurnal removal pathway for HFO-1243zf is the reaction with OH radicals, which accounts for 64% of the overall loss by homogeneous reactions at 298 K. Globally, the lifetime due to OH reaction (tau OH) was estimated to be 8.7 days under the assumption of a well-mixed atmosphere. Assuming other removal pathways, the atmospheric lifetime (tau) was estimated to be ~6 days. Considering the estimated tau OH and the measured IR absorption cross sections of HFO-1243zf in the atmospheric window (720-1,250 cm(-1)), its lifetime corrected radiative efficiency was calculated to be 0.019 W m(-2) ppbv(-1). GWP100 years for the HFO investigated, 0.29, is negligible compared to that of HFC-134a, the HFC to be potentially replaced (GWP100 years = 1,300, Hodnebrog et al. (Rev Geophys 51:300-378, 2013)). epsilon POCP for HFO-1243zf was estimated to be around 1 order of magnitude lower than that for ethylene. In conclusion, HFO 1243zf is fast degraded in the atmosphere, and it does not appreciably contribute to global warming and local/regional air pollution. Therefore, HFO-1243zf can be a suitable replacement for HFC-134a in air conditioning units. PMID- 25138555 TI - Evaluating the genotoxicity of urban PM2.5 using PCR-based methods in human lung cells and the Salmonella TA98 reverse test. AB - A number of compounds found in particulate matter with an aerodynamic diameter <2.5 (PM2.5) can interact with DNA either directly or after enzymatic transformation to induce DNA modifications. These particulate matter (PM)-induced alterations in DNA may be associated with increased frequencies of pollution associated diseases, such as lung cancer. In the present study, we applied different methods to assess the mutagenicity and genotoxicity of monthly PM2.5 organic extracts collected over a full year. We used the Salmonella assay, exposed cultured human embryonic lung fibroblasts and applied extracellular lactate dehydrogenase (LDH) and 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H tetrazolium-5-carboxyanilide inner salt (XTT) assays to assess the cytotoxicity of PM2.5 on the cells. We assessed both the expression levels of a number of DNA repair genes (using qRT-qPCR) and the genetic profile of the treated cells compared to the control. The expression levels of XRCC1 and APE1, which are involved in the first steps of base excision repair, as well as ERCC1, XPA and XPF, which encode nucleotide excision repair subunits, were analysed. The monthly mean of the PM2.5 collected was 35.16 +/- 22.06 MUg/m(3). The mutagenicity of PM2.5 to TA98 was 46 +/- 50 net revertants/m(3), while the mutagenicity to TA98 + S9 was 17 +/- 19 net revertants/m(3). The mean IC50 values were 2.741 +/- 1.414 and 3.219 +/- 2.764 m(3) of equivalent air in the XTT and LDH assays, respectively. A marked and significant increase in APE1 expression levels was observed in the exposed cells. This effect was also significantly correlated with mutagenicity (p < 0.01). No induced AFLP fragment profile alterations were detected. The proposed approach seems to be useful for integrated evaluation and for highlighting the mechanisms inducing DNA damage. PMID- 25138557 TI - Chemical extractability of As and Pb from soils across long-term abandoned metallic mine sites in Korea and their phytoavailability assessed by Brassica juncea. AB - The chemical extractability of As and Pb (by 5 mM CaCl2, 0.1 M HCl, 0.05 M NH4 (H2PO4), and aqua regia) from soils and their phytoavailability (by Brassica juncea) were assessed using 16 soil samples collected as a function of distance from mine pits across three long-term abandoned metallic mine sites. The total concentrations of As and Pb (17-41,000 and 27-10,047 mg kg(-1), respectively) decreased with increasing separation distance from the mine pits along a declining slope. However, the percentage of chemically leachable As and Pb mass (e.g., by 5 mM CaCl2, 0.1 M HCl, or 0.05 M NH4(H2PO4)) relative to total mass (e.g., by aqua regia) tended to increase exponentially with distance, indicating more chemically labile fractions present in less contaminated downgradient soils. Among soil components, extractable As concentrations were best described by coupling DCB-Al with other Al and Fe oxides. For Pb concentration, pH coupled to DCB-Al or Ox-Al provided a good predictive relationship. The inhibitory growth and uptake by plants were best correlated with the extractable concentrations by 5 mM CaCl2 and 0.1 M HCl. In conclusion, the chemical extractability and phytoavailability of As and Pb are highly influenced by the relative labile fraction in abandoned mine soils, and its distribution in soils is essentially correlated with sampling distance from mine pits. PMID- 25138556 TI - Endocrine actions of pesticides measured in the Flemish environment and health studies (FLEHS I and II). AB - Within the Flemish Environment and Health studies (FLEHS I, 2002-2006, and FLEHS II, 2007-2012), pesticide exposure, hormone levels and degree of sexual maturation were measured in 14-15-year-old adolescents residing in Flanders (Belgium). In FLEHS II, geometric mean concentrations (with 95 % confidence interval (CI)) of 307 (277-341) and 36.5 ng L(-1) (34.0-39.2) were found for p,p' dichlorophenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB). These values were respectively 26 and 60 % lower than levels in FLEHS I, 5 years earlier. Metabolites of organophosphorus pesticides (OPPs) and of para dichlorobenzene were measured for the first time in FLEHS II, yielding concentrations of 11.4, 3.27 and 1.57 MUg L(-1) for the sum of dimethyl- and diethyl phosphate metabolites and 2,5-dichlorophenol (2,5-DCP), respectively. Data on internal exposure of HCB showed a positive correlation with sexual maturation, testosterone and the aromatase index for boys and with free thyroxine (fT4) and thyroid stimulating hormone (TSH) (both boys and girls). For both p,p' DDE and HCB, a negative association with sexual development in girls was found. The OPP metabolites were negatively associated with sex hormone levels in the blood of boys and with sexual maturation (both boys and girls). The pesticide metabolite 2,5-DCP was negatively correlated with free T4, while a positive association with TSH was reported (boys and girls). These results show that even exposure to relatively low concentrations of pesticides can have significant influences on hormone levels and the degree of sexual maturation in 14-15-year old adolescents. PMID- 25138558 TI - Leaf-age and soil-plant relationships: key factors for reporting trace-elements hyperaccumulation by plants and design applications. AB - Relationships between the trace-elements (TE) content of plants and associated soil have been widely investigated especially to understand the ecology of TE hyperaccumulating species to develop applications using TE phytoextraction. Many studies have focused on the possibility of quantifying the soil TE fraction available to plants, and used bioconcentration (BC) as a measure of the plants ability to absorb TE. However, BC only offers a static view of the dynamic phenomenon of TE accumulation. Accumulation kinetics are required to fully account for TE distributions in plants. They are also crucial to design applications where maximum TE concentrations in plant leaves are needed. This paper provides a review of studies of BC (i.e. soil-plant relationships) and leaf age in relation to TE hyperaccumulation. The paper focuses of Ni and Mn accumulators and hyperaccumulators from New Caledonia who were previously overlooked until recent Ecocatalysis applications emerged for such species. Updated data on Mn hyperaccumulators and accumulators from New Caledonia are also presented and advocate further investigation of the hyperaccumulation of this element. Results show that leaf-age should be considered in the design of sample collection and allowed the reclassification of Grevillea meisneri known previously as a Mn accumulator to a Mn hyperaccumulator. PMID- 25138559 TI - Environmental chemicals mediated the effect of old housing on adult health problems: US NHANES, 2009-2010. AB - Housing conditions affect occupants continuously, and health interventions have shown a positive association between housing investment or improvement and occupant's health. However, the sources of the housing problems were less understood. Since it was observed that lead dust and chloroanisoles released from housing (materials) as indoor pollutants affected child's health, we now aimed to examine the relationships among built year, environmental chemicals and individual health in adults in a national and population-based setting. Data were retrieved from the US National Health and Nutrition Examination Survey, 2009 2010, including demographics, housing characteristics, self-reported health status, biomarkers and blood and urinary chemical concentrations. Adults aged 20 and above were included for statistical analysis (n = 5,793). Analysis involved chi-square test, t test, and survey-weighted general linear regression and logistic regression modelling. People who resided in older housing built before 1990 tended to report chronic bronchitis, liver problems, stroke, heart failure, diabetes, asthma and emphysema. Higher values in HDL cholesterol, blood lead and blood cadmium and having positive responses of hepatitis A, B, C and E antibodies among occupants were also observed. Furthermore, higher environmental chemical concentrations related to old housing including urinary cadmium, cobalt, platinum, mercury, 2,5-dichlorophenol and 2,4-dichlorophenol concentrations and mono-cyclohexyl phthalate and mono-isobutyl phthalate metabolites were shown in occupants as well. Older housing (>=30 years) seemed to contribute to the amount of environmental chemicals that affected human health. Regular monitoring, upgrading and renovation of housing to remove environmental chemicals and policy to support people in deprived situations against environmental injustice would be needed. PMID- 25138560 TI - Cancer risks and long-term community-level exposure to pentachlorophenol in contaminated areas, China. AB - Widespread use of pentachlorophenol (PCP) in schistosomiasis endemic areas had led to ubiquitous exposure to PCP and its residues. Numerous studies had revealed that occupational PCP exposure probably increased risk of cancers, but whether long-term community-level exposure to PCP generates the similarly carcinogenic effect, seldom studies focused on it. This study was to explore the cancer risks of long-term community-level PCP exposure from drinking water in a Chinese general population. Incident (2009-2012) cancer records were identified by local government national registry. And PCP concentration of raw drinking water samples in each district was measured by GC-MS/MS analysis for further division of three PCP exposure categories by interquartile range (high vs. medium vs. low). Internal comparisons were performed, and standard rate ratio was calculated to describe the relationship between PCP exposure and cancer risks by using low exposure group as the reference group. PCP was detected in all 27 raw drinking water samples ranging from 11.21 to 684.00 ng/L. A total of 6,750 cases (4,409 male and 2,341 female cases) were identified, and age-standardized rate (world) was 154.95 per 100,000 person-years. The cancer incidence for the high-exposure group was remarkably high. Internal comparisons indicated that high PCP exposure might be positively associated with high cancer risks in the community population, particularly for leukemia (SRR = 5.93, 95 % CI = 5.24-6.71), maligant lymphoma (SRR = 2.27, 95 % CI = 2.10-2.54), and esophageal cancer (SRR = 2.42, 95 % CI = 2.35-2.50). Long-term community-level exposure to PCP was probably associated with hemolymph neoplasm, neurologic tumors, and digestive system neoplasm. PMID- 25138561 TI - Differential effect of water-soluble chitin on collagen synthesis of human bone marrow stem cells and human periodontal ligament stem cells. AB - Human bone marrow stem cells (hBMSCs) represent a promising regenerative material because of their mutipotency, including their ability to regenerate collagenous soft tissues. We previously found that water-soluble chitin (WSC) enhances the ability of human periodontal ligament stem cells (hPDLSCs) to synthesize collagen tissue. The aim of this study was to determine the effects of WSC on hBMSCs and hPDLSCs for the collagen synthesis both in vitro and in vivo. hBMSCs and hPDLSCs were isolated and expanded with or without 0.3 mg/mL WSC. A series of in vitro and in vivo analyses were performed to evaluate their characteristics as stem cell populations. Then, collagen and hydroxyproline assays were conducted using both in vitro and in vivo assay models, and the real-time polymerase chain reaction was performed to analyze the expression of collagen-related markers. WSC treated and nontreated hBMSCs and hPDLSCs were transplanted into immunocompromised mice, and histology and immunohistochemistry analyses were conducted after 8 weeks. The in vitro results showed that those cells possessed the characteristics of mesenchymal stem cells. The amount of soluble collagen synthesized was significantly greater in WSC-treated hBMSCs than in the nontreated group; conversely, treatment of hPDLSCs with WSC decreased the formation of soluble collagen. The amount of insoluble collagen synthesized was greater in the WSC-treated groups than in the nontreated groups for both hBMSCs and hPDLSCs. The hydroxyproline contents of the regenerated soluble and insoluble collagens were similar. The expressions of mRNA for collagen types I-V, hyaluronic acid synthase 1 (HAS1), HAS2, and HAS3, and the LOX family were higher in WSC-treated hPDLSCs than in the nontreated group, whereas WSC increased the expression of collagen type III and decreased that of collagen type I in hBMSCs. The histology and immunohistochemistry results revealed that WSC significantly increased the amount of collagen formed in vivo by both types of stem cells. Collectively, treatment with WSC significantly enhanced the collagen-forming potentials of hBMSCs and hPDLSCs, but the collagen they produced exhibited distinctively different characteristics. These findings suggest that the appropriate stem-cell source should be chosen based on the purpose of the required regenerated tissue. PMID- 25138562 TI - The expression of glucocorticoid receptor is negatively regulated by active androgen receptor signaling in prostate tumors. AB - The glucocorticoid and androgen receptors (GR and AR) can commonly regulate up to 50% of their target genes in prostate cancer (PCa) cells. GR expression is stimulated by castration therapy, which has been proposed to be one mechanism that compensates for AR signaling blockade and promotes castration-resistant PCa (CRPC) progression. However, whether GR functions as a driver for CRPC or a marker reflecting AR activity remains unclear. Here, we applied PCa tissue microarrays to show that GR protein levels were elevated by castration therapy, but reduced to pre-castration levels when tumors were at the CRPC stage. Using subrenal capsule xenograft models, we showed that GR expression was inversely correlated with AR and PSA expressions. GR expression levels are not associated with tumor invasion and metastasis phenotypes. In castration-resistant C4-2 xenografts expressing AR shRNA, regressing tumors induced by AR knockdown expressed higher levels of GR and lower levels of PSA than non-regressing tumors. Immunoblotting and real-time PCR assays further showed that AR knockdown or AR antagonists increased GR expression at both mRNA and protein levels. ChIP combined with DNA sequencing techniques identified a negative androgen responsive element (nARE) 160K base pairs upstream of the GR gene. Gel shift assays confirmed that AR directly interacted with the nARE and luciferase assays demonstrated that the nARE could mediate transcription repression by ligand activated AR. In conclusion, GR expression is negatively regulated by AR signaling and may serve as a marker for AR signaling in prostate tumors. PMID- 25138563 TI - Beta-blocking agents in cardiovascular disease; are they here to stay? PMID- 25138564 TI - Allergen analysis of sea urchin roe using sera from five patients. AB - BACKGROUND: Sea urchin roe can cause anaphylactic reactions the first time they are consumed; therefore, careful clinical attention should be paid to their effects. However, no previous study has examined the allergens in sea urchin roe using sera from more than one patient. We attempted to identify sea urchin allergens using sera from 5 patients with sea urchin allergies. METHODS: We enrolled 5 patients with relevant medical histories, positive results on a skin prick test and/or a food challenge test, and high levels of sea urchin-specific IgE in an enzyme-linked immunosorbent assay. We performed SDS-PAGE, immunoblotting, immunoblot inhibition, and N-terminal amino acid sequence detection. RESULTS: Ten protein bands ranging from 18 to 170 kDa were detected in more than 2 patients' sera. In immunoblotting, the protein band for the 170-kDa major yolk protein was recognized by 4 of the 5 sera. Furthermore, the reaction between IgE and the protein band for egg cortical vesicle protein (18 kDa) was inhibited by the addition of salmon roe extract. CONCLUSION: Major yolk protein was confirmed to be one of the main allergens in sea urchin roe. In addition, egg cortical vesicle protein (18 kDa) was demonstrated to be an important protein for cross-reactivity with salmon roe. PMID- 25138566 TI - 'They said it was bronchiolitis; is it going to turn into asthma doctor?'. AB - Acute bronchiolitis is a common paediatric disease of infancy. Its association with subsequent asthma development has puzzled clinicians and epidemiologists for decades. This article reviews the current state of knowledge regarding the role of acute bronchiolitis in the inception of asthma. There is little doubt that acute bronchiolitis is associated with an increased risk of recurrent wheezing throughout the primary school years although the direction of causality--i.e. whether bronchiolitis in infancy leads to asthma or it merely represents the first clinical presentation of predisposition to asthma--is uncertain. Existing evidence suggests that both host factors (e.g. prematurity, atopic predisposition) and acute viral infection characteristics (e.g. type of virus, severity) are operating in this relationship, perhaps with variable involvement in different individuals. Further clarification of these issues will help paediatricians provide evidence-based information regarding the long-term prognosis of this common disease to the families, and at the same time, it will facilitate prophylactic approaches and therapeutic strategies. PMID- 25138567 TI - Teaching nursing concepts through an online discussion board. AB - Barriers to course content engagement and student learning in nursing education abound. Some of these barriers include content overload, classroom time constraints, and large student numbers. One way to overcome these issues is the implementation of active learning strategies in the classroom. Despite the positive learning outcomes associated with active learning strategies described in the education literature, traditional passive learning strategies continue to be used by nurse educators in the classroom. This article details the results of a pilot study using an active teaching strategy-an online discussion board-which was designed to improve the learning engagement of beginning nursing students enrolled in their first face-to-face nursing course. The results of the semester long pilot study indicated a favorable student response to the active teaching strategy and improved overall success in the course by the students who participated fully in the online discussions. PMID- 25138568 TI - Integrating Reiki and community-engaged scholarship: an interdisciplinary educational innovation. AB - To provide students with a meaningful holistic care experience while integrating community-engaged scholarship, students partnered with a Reiki-prepared faculty member within a nurse-managed community clinic to offer Reiki to the clients and participate in the evaluation of the effectiveness of the modality. This article describes how students and faculty integrated holistic care, scholarship, and community engagement. This experience provided the students with an opportunity to embrace the art and science of holistic nursing while obtaining experience in measuring outcomes. PMID- 25138565 TI - Childhood maltreatment and the risk of pre-pregnancy obesity and excessive gestational weight gain. AB - The objective of this study was to estimate whether maternal history of childhood maltreatment was associated with pre-pregnancy obesity or excessive gestational weight gain. Pregnant women (n = 472) reported pre-pregnancy weight and height and gestational weight gain and were followed up to 16 years post-partum when they reported maltreatment on the Childhood Trauma Questionnaire (CTQ). CTQ score ranged from no maltreatment (25) to severe maltreatment (125). Prenatal mental health modified the association between CTQ score and maternal weight (P < 0.15), and thus stratified models are presented. After adjusting for race, prenatal tobacco, marijuana and alcohol use, a one standard deviation (1 SD) increase in CTQ score was associated with a 45% increase in the risk of pre-pregnancy obesity among the 141 women with elevated anxiety (>=75th percentile on the State Trait Anxiety Inventory) [relative risk, RR (95% confidence interval, CI): 1.45 (1.12, 1.88)], but was not associated among less anxious (<75th percentile) women [RR (95% CI): 1.10 (0.81, 1.51)]. Risk of excessive gestational weight gain was higher [adjusted RR (95% CI): 1.21 (1.07, 1.37)] with every 1 SD increase in CTQ score for anxious women. No association was observed for less anxious women [adjusted RR (95% CI): 0.89 (0.78, 1.02)]. Prenatal depression similarly modified the association between maltreatment and weight gain. Factors such as psychological status and traumatic experiences in early childhood may contribute to pre-pregnancy obesity and excessive gestational weight gain. PMID- 25138569 TI - Three-calendar-year Bachelor of Science in Nursing: an innovative curriculum program. AB - The 3-calendar-year Bachelor of Science in Nursing (BSN) curriculum program was developed to facilitate a quicker entry into professional nursing practice. This program offered many advantages, including financial and time-saving benefits for students, more efficient use of campus facilities, and flexibility in faculty scheduling. Evaluation of the program showed benefits in the success rate of course-work, in retention and graduation rates, and in subsequent NCLEX-RN pass rates. The NCLEX-RN pass rate for students in the 3-calendar-year BSN program was 98.33%, compared with the national average pass rate (88.01%) for the same 5-year period for first-time test takers. The 3-calendar-year BSN program met the needs of both traditional and nontraditional students. It produced quality nurse graduates who were successful NCLEX-RN first-time test takers. The program has potential to be adopted by other universities with a student base composed of individuals of modest resources and diverse backgrounds. PMID- 25138570 TI - Meaningful learning: theoretical support for concept-based teaching. AB - Novice nurses' inability to transfer classroom knowledge to the bedside has been implicated in adverse patient outcomes, including death. Concept-based teaching is a pedagogy found to improve knowledge transfer. Concept-based teaching emanates from a constructivist paradigm of teaching and learning and can be implemented most effectively when the underlying theory and principles are applied. Ausubel's theory of meaningful learning and its construct of substantive knowledge integration provides a model to help educators to understand, implement, and evaluate concept-based teaching. Contemporary findings from the fields of cognitive psychology, human development, and neurobiology provide empirical evidence of the relationship between concept-based teaching, meaningful learning, and knowledge transfer. This article describes constructivist principles and meaningful learning as they apply to nursing pedagogy. PMID- 25138571 TI - Habitat differences influence genetic impacts of human land use on the American beech (Fagus grandifolia). AB - Natural reforestation after regional forest clearance is a globally common land use sequence. The genetic recovery of tree populations in these recolonized forests may depend on the biogeographic setting of the landscape, for instance whether they are in the core or in the marginal part of the species' range. Using data from 501 individuals genotyped across 7 microsatellites, we investigated whether regional differences in habitat quality affected the recovery of genetic variation in a wind-pollinated tree species, American beech (Fagus grandifolia) in Massachusetts. We compared populations in forests that were recolonized following agricultural abandonment to those in remnant forests that have only been logged in both central inland and marginal coastal regions. Across all populations in our entire study region, recolonized forests showed limited reduction of genetic diversity as only observed heterozygosity was significantly reduced in these forests (H(O) = 0.520 and 0.590, respectively). Within inland region, this pattern was observed, whereas in the coast, recolonized populations exhibited no reduction in all genetic diversity estimates. However, genetic differentiation among recolonized populations in marginal coastal habitat increased (F(st) logged = 0.072; F(st) secondary = 0.249), with populations showing strong genetic structure, in contrast to inland region. These results indicate that the magnitude of recovery of genetic variation in recolonized populations can vary at different habitats. PMID- 25138572 TI - Improving immunogenicity and efficacy of vaccines for genital herpes containing herpes simplex virus glycoprotein D. AB - No vaccines are approved for prevention or treatment of genital herpes. The focus of genital herpes vaccine trials has been on prevention using herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) alone or combined with glycoprotein B. These prevention trials did not achieve their primary end points. However, subset analyses reported some positive outcomes in each study. The most recent trial was the Herpevac Trial for Women that used gD2 with monophosphoryl lipid A and alum as adjuvants in herpes simplex virus type 1 (HSV-1) and HSV-2 seronegative women. Unexpectedly, the vaccine prevented genital disease by HSV-1 but not HSV-2. Currently, HSV-1 causes more first episodes of genital herpes than HSV-2, highlighting the importance of protecting against HSV-1. The scientific community is conflicted between abandoning vaccine efforts that include gD2 and building upon the partial successes of previous trials. We favor building upon success and present approaches to improve outcomes of gD2-based subunit antigen vaccines. PMID- 25138573 TI - The influence of antioxidant THPC on the properties of polymer gel dosimeter. AB - In order to decrease the negative influence of oxygen to the response of PAG dosimeters THPC has been added to the gel in the role of scavenger. Apart from the decreased influence of oxygen, THPC also influences other properties of gel dosimeters. This study examines these influences and their quantification. Previous studies have shown that increasing the concentration of THPC causes a decreasing response of the dosimeter (as measured in the relaxation rate R2). Evaluation of the IR spectrum of gels irradiated by a variety of doses has shown that it is caused mostly by the changed structure of the arising polymer, not due to the decreased polymerization. THPC also changes the kinetics of the subsequent reactions in the gel after the end of irradiation. THPC has its influence also on the size of the dose response overshoot that happens in the areas of steep dose gradients. An easy model of action in the gel was suggested, which allows one to estimate the size and kinetics of the changed response of the dosimeter after the end of irradiation depending on the content of THPC, the size of the dose and the dose gradient. PMID- 25138574 TI - Comparative effects of metformin and pioglitazone on YKL-40 in type 2 diabetes: a randomized clinical trial. AB - PURPOSE: Metformin and pioglitazone are believed to exert their long-term benefits by means of amelioration of chronic low-grade inflammation, a key event in development of diabetes and its long-term complications. The present trial was designed to investigate the comparative efficacy of the two anti-diabetes medications on serum concentrations of YKL-40, a novel marker of inflammation. METHODS: In a parallel-group, open-label, randomized trial setting (ClinicalTrials.gov Identifier No. NCT01521624), 84 newly diagnosed, medication naive type 2 diabetes patients were assigned to metformin 1,000 mg daily (n = 42) or pioglitazone 30 mg daily (n = 42). Serum concentrations of YKL-40, along with highly sensitive C-reactive protein, indices of glycemic control and lipid profile were measured at baseline and after 3 months. RESULTS: In the analyzed sample (metformin = 40, pioglitazone = 42), both medications were equally effective with regard to control of hyperglycemia, and hsCRP reduction (p > 0.05). However, metformin caused a significant decline in weight (p = 0.005), BMI (p = 0.004), and total cholesterol levels (p = 0.028) of the patients. Metformin also significantly reduced YKL-40 concentrations after 3 months (1.90 +/- 17 vs. 1.66 +/- 0.15 ug/L, p = 0.019). The amount of change in the pioglitazone arm did not reach statistical significance (2.18 +/- 0.14 vs. 2.25 +/- 0.16 ug/L, p = 0.687). When compared, metformin was significantly more effective than pioglitazone with respect to YKL-40 reduction in both univariate (p = 0.020, effect size = 6.7%) and multivariate models (p = 0.047, effect size = 5.7%). CONCLUSIONS: Metformin is more effective in reduction of YKL-40 concentration in short term and the effect seems to be independent of degree of glycemic control, or hsCRP reduction. PMID- 25138576 TI - Telomere-centric genome repatterning determines recurring chromosome number reductions during the evolution of eukaryotes. AB - Whole-genome duplication (WGD) is central to the evolution of many eukaryotic genomes, in particular rendering angiosperm (flowering plant) genomes much less stable than those of animals. Following repeated duplication/triplication(s), angiosperm chromosome numbers have usually been restored to a narrow range, as one element in a 'diploidization' process that re-establishes diploid heredity. In several angiosperms affected by WGD, we show that chromosome number reduction (CNR) is best explained by intra- and/or inter-chromosomal crossovers to form new chromosomes that utilize the existing telomeres of 'invaded' and centromeres of 'invading' chromosomes, the alternative centromeres and telomeres being lost. Comparison with the banana (Musa acuminata) genome supports a 'fusion model' for the evolution of rice (Oryza sativa) chromosomes 2 and 3, implying that the grass common ancestor had seven chromosomes rather than the five implied by a 'fission model.' The 'invading' and 'invaded' chromosomes are frequently homoeologs, originating from duplication of a common ancestral chromosome and with greater than-average DNA-level correspondence to one another. Telomere-centric CNR following recursive WGD in plants is also important in mammals and yeast, and may be a general mechanism of restoring small linear chromosome numbers in higher eukaryotes. PMID- 25138577 TI - A unique case of an indolent myometrial T-cell lymphoproliferative disorder with phenotypic features resembling uterine CD8+ resident memory T cells. AB - OBJECTIVE: Indolent extranodal T-cell lymphoproliferative disorders have recently been described as new entities in the gastrointestinal tract and acral sites displaying clonal T-cell receptor (TCR) rearrangement and nonactivated cytotoxic CD8+ T-cell phenotypes. METHODS/RESULTS: We report a unique case of an atypical myometrial T-cell lymphoproliferation in a 39-year-old multiparous woman, which shares many of the features mentioned above: CD8+/TIA1+/granzyme B- phenotype, clonal TCR rearrangement and indolent course. CONCLUSION(S): We hypothesize that it might derive from a subset of uterine nonrecirculating CD8+ resident memory T cells expanded after repeated exposure to allo-extravillous trophoblastic antigen. PMID- 25138575 TI - A therapeutic approach to treat prostate cancer by targeting Nm23-H1/h-Prune interaction. AB - Nm23-H1 is a metastasis suppressor gene whose overexpression is associated with both reduced cell motility in various cancers and increased metastatic potential in neuroblastomas, osteosarcomas, and hematological malignances. We previously reported that Nm23-H1 exerts tumor suppressor action in prostate cancer cells and that h-Prune, which is overexpressed in various tumor types, binds Nm23-H1. Moreover, blockage of the Nm23-H1/h-Prune interaction with a competitive permeable peptide (CPP) attenuates migration of breast and neuroblastoma cells. This series of events suggests that the Nm23-H1/h-Prune protein complex regulates cancer progression and that its specific impairment could be a new therapeutic strategy in oncology. We found that CPP leads to inhibition of the AKT/mTORv and NF-kBv signaling pathways and also activates apoptosis. To obtain a proof-of concept of our hypothesis, we used a xenograft model of prostate cancer to evaluate whether impairment of this complex using CPP results in an anti-tumoral effect. Using a mouse orthotopic model with bioluminescent imaging, we show evidences that CPP reduces prostate cancer metastases formation. In conclusion, CPP being able to impair formation of the h-Prune/Nm23-H1 complex holds promise for the treatment of prostate cancer. PMID- 25138578 TI - Usefulness of the diameter-axial-polar nephrometry score for predicting perioperative parameters in robotic partial nephrectomy. AB - PURPOSE: The present study aimed to verify the association between diameter-axial polar (DAP) nephrometry and surgical outcomes, postoperative renal function, and perioperative complications in patients undergoing robotic partial nephrectomy (RPN). METHODS: Diameter-axial-polar nephrometry was assessed using computed tomography or magnetic resonance imaging on 158 patients who received RPN between July 2007 and February 2013. Demographic data, surgical data, and perioperative complications were recorded, and percent change between the preoperative and last estimated glomerular filtration rate (eGFR) was determined. Linear regression analysis was conducted to assess the relationship between the DAP sum score and warm ischemia time (WIT), estimated blood loss (EBL), and percent decrease in eGFR. Multivariable linear regression analysis was conducted to determine the relationship between each DAP scoring parameter and surgical outcomes. RESULTS: The median patient age was 50.5 years and median DAP sum score was 6. On linear regression, the DAP sum score was associated with WIT and EBL. On multivariable regression, all DAP parameters were associated with WIT, but the polar distance was not associated with EBL. Patients with a higher DAP sum score showed greater decrease in eGFR after RPN. Patients with a DAP sum score of 6 or higher had a higher risk of major complications than those with a DAP sum score below 6. CONCLUSIONS: Diameter-axial-polar nephrometry predicted WIT and EBL in patients who underwent RPN. It was also associated with the decrease in eGFR and rate of major perioperative complications, and thus can be useful for surgical planning or patient counseling before RPN. PMID- 25138579 TI - The impact of adding low-dose oral desmopressin therapy to tamsulosin therapy for treatment of nocturia owing to benign prostatic hyperplasia. AB - PURPOSE: To evaluate the efficacy and safety of adding a low-dose oral desmopressin to tamsulosin therapy for treatment of nocturia in patients with benign prostatic hyperplasia (BPH). METHODS: Eligible patients with BPH and nocturia >=2/night were randomly allocated to two treatment groups; the first of which received 3-month treatment scheme of daily oral dose of tamsulosin OCAS 0.4 mg and desmopressin MELT 60 mcg (D/T group), while the second one received tamsulosin OCAS 0.4 mg only (T group). Patients were followed on monthly basis and changes in the parameters from baseline to 3 months after treatment were assessed on I-PSS/QoL questionnaire, 7-day voiding diary, urinalysis, serum sodium, abdominal ultrasonography and uroflowmetry. RESULTS: A total of 248 patients were included within the study; 123 patients in the combined D/T group and 125 patients in T group. The frequencies of night voids decreased by 64.3% in D/T group compared to 44.6% in T group. The first sleep period, significantly increased from 82.1 to 160.0 min and from 83.2 to 123.8 min in D/T and T group, respectively; and significant differences between both groups were observed at the end of study (p < 0.001). I-PSS, QoL score, post-void residual urine volume and Q max were significantly improved with no statistical difference between both groups. No serious adverse effects were reported in both groups. CONCLUSION: The addition of low-dose oral desmopressin therapy to an alpha-blocker tamsulosin provides effective treatment for nocturia in patients with LUTS/BPH. PMID- 25138580 TI - Carbon nanofibers modified with heteroatoms as metal-free catalysts for the oxidative dehydrogenation of propane. AB - Carbon nanofibres (CNFs) were modified with B and P by an ex situ approach. In addition, CNFs doped with N were prepared in situ using ethylenediamine as the N and C source. After calcination, the doped CNFs were used as catalysts for the oxidative dehydrogenation of propane. For B-CNFs, the effects of boron loading and calcination temperature on B speciation and catalytic conversion were studied. For the same reaction temperatures and conversions, B- and P-doped CNFs exhibited higher selectivities to propene than pristine CNFs. The N-CNFs were the most active but the least selective of the catalysts tested here. Our results also show that the type of P precursor affects the selectivity to propene and that CNFs modified using triphenylphosphine as the precursor provided the highest selectivity at isoconversion. PMID- 25138581 TI - Fluorescence-guided surgery improves outcome in an orthotopic osteosarcoma nude mouse model. AB - In order to develop a model for fluorescence-guided surgery (FGS), 143B human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the intramedullary cavity of the tibia in nude mice. The fluorescent areas of residual tumors after bright-light surgery (BLS) and FGS were 10.2 +/- 2.4 mm(2) and 0.1 +/- 0.1 mm(2) , respectively (p<0.001). The BLS-treated mice and BLS+cisplatinum (CDDP)-treated mice had significant recurrence. In contrast, the FGS mice and FGS+CDDP mice had very little recurring tumor growth. Disease-free survival (DFS) in the BLS-, BLS+CDDP-, FGS-, and FGS+CDDP-treated mice was 12.5%, 37.5%, 75.0%, and 87.5%, respectively. The FGS-treated mice had a significantly higher DFS rate than the BLS-treated mice (p=0.021). The FGS+CDDP-treated mice had significantly higher DFS rate than the BLS+CDDP-treated mice (p=0.043). Although chemotherapy significantly reduced multiple metastases (p=0.033), there was no significant correlation between FGS and lung metastasis. FGS significantly reduced the recurrence of the primary tumor but did not reduce lung metastasis. The combination of FGS and adjuvant CDDP reduced tumor recurrence and prevented multiple metastases. FGS and adjuvant chemotherapy should be performed as early as possible in the disease to prevent both recurrence and metastatic development. PMID- 25138582 TI - Diet, Physical Activity, Lifestyle Behaviors, and Prevalence of Childhood Obesity in Irish Children: The Cork Children's Lifestyle Study Protocol. AB - BACKGROUND: Childhood obesity is complex, and its aetiology is known to be multifaceted. The contribution of lifestyle behaviors, including poor diet and physical inactivity, to obesity remains unclear. Due to the current high prevalence, childhood obesity is an urgent public health priority requiring current and reliable data to further understand its aetiology. OBJECTIVE: The objective of this study is to explore the individual, family, and environmental factors associated with childhood overweight and obesity, with a specific focus on diet and physical activity. A secondary objective of the study is to determine the average salt intake and distribution of blood pressure in Irish children. METHODS: A cross-sectional survey was conducted of children 8-11 years old in primary schools in Cork, Ireland. Urban schools were selected using a probability proportionate to size sampling strategy, and a complete sample of rural schools from one area in Cork County were invited to participate. Information collected included physical measurement data (anthropometric measurements, blood pressure), early morning spot and 24 hour urine samples, a 3 day estimated food diary, and 7 days of accelerometer data. Principal- (school head) reported, parent/guardian reported, and child-reported questionnaires collected information on lifestyle behaviors and environmental attributes. The Cork Children's Lifestyle Study (CCLaS) was designed by the Department of Epidemiology and Public Health in University College Cork, Ireland in 2011 and 2012. Piloting and modification of study methods was undertaken. Data collection took place between April 2012 and June 2013. RESULTS: Overall, 27/46 schools and 1075/1641 children, of which 623 were boys, participated. Preliminary data analysis is underway. It is anticipated that the results of the CCLaS study will be available in late 2014. CONCLUSIONS: The CCLaS study has collected in-depth data on a wide range of individual, family, social, and environmental correlates which will allow us to access multilevel influences on childhood obesity. This study will contribute to the evidence base by highlighting current knowledge and gaps regarding the predominant drivers of childhood obesity. PMID- 25138584 TI - Scaphocephaly and cranial vault reconstruction: Renier's 'H' technique. AB - BACKGROUND: Resulting from an early fusion of the sagittal suture, scaphocephaly (SC) is the most frequent form of all craniosynostosis and represents 40-60% of all cases. The scope of this study is to describe the first series of Renier's 'H' technique to be applied in children with SC outside of France. METHODS: A consecutive review is made of the medical records of children hospitalized in the last 6 years (between March 2007 and March 2013) with isolated SC in whom Renier's 'H' technique was performed. RESULTS: Thirteen children met the criteria for inclusion in the study. Considering medical evaluation and parental satisfaction, the evaluation of postsurgical cranial reconstruction was classified as satisfactory in all cases. CONCLUSIONS: We consider the Renier's H technique to be effective in the cranial reshaping of children with isolated SC, with satisfactory esthetic postsurgical results. PMID- 25138585 TI - syn-1,2-carboboration of alkynes with borenium cations. AB - The reaction of 8-(trimethylsiloxy)quinoline (QOTMS) with BCl3 and (aryl)BCl2 forms QOBCl2 and QOBCl(aryl). The subsequent addition of stoichiometric AlCl3 follows one of two paths, dependent on the steric demands of the QO ligand and the electrophilicity of the resulting borenium cation. The phenyl- and 5 hexylthienylborenium cations, QOBPh(+) and QOBTh(+), are formed, whereas QOBCl(+) is not. Instead, AlCl3 preferentially binds with QOBCl2 at oxygen, forming QOBCl2 ?AlCl3, rather than abstracting chloride. A modest increase in the steric demands around oxygen, by installing a methyl group at the 7-position of the quinolato ligand, switches the reactivity with AlCl3 back to chloride abstraction, allowing formation of Me 2QOBCl(+). All the prepared borenium cations are highly chlorophilic and exhibit significant interaction with AlCl4(-) resulting in an equilibrium concentration of Lewis acidic "AlCl3" species. The presence of "AlCl3(") species limits the alkyne substrates compatible with these borenium systems, with reaction of [QOBPh][AlCl4 ] with 1-pentyne exclusively yielding the cyclotrimerised product, 1,3,5-tripropylbenzene. In contrast, QOBPh(+) and QOBTh(+) systems effect the syn-1,2-carboboration of 3-hexyne. DFT calculations at the M06-2X/6-311G(d,p)/PCM(DCM) level confirm that the higher migratory aptitude of Ph versus Me leads to a lower barrier to 1,2-carboboration relative to 1,1-carboboration. PMID- 25138586 TI - The preparation and structure of Ge3F8 - a new mixed-valence fluoride of germanium, a convenient source of GeF2. AB - The new binary mixed-valence fluoride of germanium, Ge3F8, has been obtained by heating GeF4 with powdered Ge in an autoclave (390 K/4 bar/48 h). The structure contains pyramidal Ge(II)F3 and octahedral Ge(IV)F6 units, linked by fluoride bridges. The new compound is the missing member of the series (GeF2)n.GeF4 (n = 2, 4, or 6). Sublimation of (GeF2)n.GeF4in vacuo provides a convenient source of GeF2 in ca. 30% overall yield. PMID- 25138583 TI - The Lablite project: a cross-sectional mapping survey of decentralized HIV service provision in Malawi, Uganda and Zimbabwe. AB - BACKGROUND: In sub-Saharan Africa antiretroviral therapy (ART) is being decentralized from tertiary/secondary care facilities to primary care. The Lablite project supports effective decentralization in 3 countries. It began with a cross-sectional survey to describe HIV and ART services. METHODS: 81 purposively sampled health facilities in Malawi, Uganda and Zimbabwe were surveyed. RESULTS: The lowest level primary health centres comprised 16/20, 21/39 and 16/22 facilities included in Malawi, Uganda and Zimbabwe respectively. In Malawi and Uganda most primary health facilities had at least 1 medical assistant/clinical officer, with average 2.5 and 4 nurses/midwives for median catchment populations of 29,275 and 9,000 respectively. Primary health facilities in Zimbabwe were run by nurses/midwives, with average 6 for a median catchment population of 8,616. All primary health facilities provided HIV testing and counselling, 50/53 (94%) cotrimoxazole preventive therapy (CPT), 52/53 (98%) prevention of mother-to-child transmission of HIV (PMTCT) and 30/53 (57%) ART management (1/30 post ART-initiation follow-up only). All secondary and tertiary level facilities provided HIV and ART services. In total, 58/81 had ART provision. Stock-outs during the 3 months prior to survey occurred across facility levels for HIV test-kits in 55%, 26% and 9% facilities in Malawi, Uganda and Zimbabwe respectively; for CPT in 58%, 32% and 9% and for PMTCT drugs in 26%, 10% and 0% of facilities (excluding facilities where patients were referred out for either drug). Across all countries, in facilities with ART stored on-site, adult ART stock-outs were reported in 3/44 (7%) facilities compared with 10/43 (23%) facility stock-outs of paediatric ART. Laboratory services at primary health facilities were limited: CD4 was used for ART initiation in 4/9, 5/6 and 13/14 in Malawi, Uganda and Zimbabwe respectively, but frequently only in selected patients. Routine viral load monitoring was not used; 6/58 (10%) facilities with ART provision accessed centralised viral loads for selected patients. CONCLUSIONS: Although coverage of HIV testing, PMTCT and cotrimoxazole prophylaxis was high in all countries, decentralization of ART services was variable and incomplete. Challenges of staffing and stock management were evident. Laboratory testing for toxicity and treatment effectiveness monitoring was not available in most primary level facilities. PMID- 25138587 TI - Unusual osteoporotic stress fracture: adjacent bilateral pedicle fractures. PMID- 25138589 TI - Effect of crude extracts of selected actinomycetes on biofilm formation of A. schindleri, M. aci, and B. cereus. AB - Actinomycetes are well known group of gram positive bacteria for their potential to produce antibiotics. This study sought to assess the ability of the selected actinomycetes to control biofilm forming bacteria isolated from different dental plaque samples. On the basis of morphological differences three out of ten different dental plaque bacterial isolates were selected for further study. These isolates were biochemically and genetically characterized and were identified as Acinetobacter schinndleri, Moraxella aci, and Bacillus cereus. Antibiotic resistant profile was measured through disc diffusion method and found that all three isolates were moderately sensitive to ofloxacin and erythromycin and resistant to trimethoprim. Antibacterial activity of ten different Streptomyces strains was assessed through an agar plug and well diffusion method against three dental biofilm forming bacteria. Two Streptomyces strains named as S. erythrogriseus and S. labedae showed good antibacterial activity against Moraxella and Acinetobacter strains. Ability of the four active antibiotic producing strains to inhibit biofilm formation was assessed using microtiter biofilm detection assay. It was found that biofilm forming ability of Acinetobacter and Moraxella was inhibited by S. labedae an antibiotic producing strain, while S. macrosporeus can only inhibit biofilm formation by B. cereus. PMID- 25138588 TI - Ibrutinib inhibits collagen-mediated but not ADP-mediated platelet aggregation. AB - The BTK (Bruton's tyrosine kinase) inhibitor ibrutinib is associated with an increased risk of bleeding. A previous study reported defects in collagen- and adenosine diphosphate (ADP)-dependent platelet responses when ibrutinib was added ex vivo to patient samples. Whereas the collagen defect is expected given the central role of BTK in glycoprotein VI signaling, the ADP defect lacks a mechanistic explanation. In order to determine the real-life consequences of BTK platelet blockade, we performed light transmission aggregometry in 23 patients receiving ibrutinib treatment. All patients had reductions in collagen-mediated platelet aggregation, with a significant association between the degree of inhibition and the occurrence of clinical bleeding or bruising (P=0.044). This collagen defect was reversible on drug cessation. In contrast to the previous ex vivo report, we found no in vivo ADP defects in subjects receiving standard doses of ibrutinib. These results establish platelet light transmission aggregometry as a method for gauging, at least qualitatively, the severity of platelet impairment in patients receiving ibrutinib treatment. PMID- 25138590 TI - Effects of handling on fear reactions in young Icelandic horses. AB - REASONS FOR PERFORMING THE STUDY: Inclusion of objective temperament tests at practical horse breeding evaluations is of increased interest. It has been debated whether such tests may involve human handling, since there may be considerable differences in horses' handling experience. OBJECTIVES: To investigate the effect of a short-term standardised handling procedure on reactions of young horses in 2 types of fear tests (including and excluding human handling). STUDY DESIGN: An experimental study with 3-year-old Icelandic horses (n = 24). METHODS: Handled horses (n = 12) were trained according to a standardised handling procedure whereas controls (n = 12) remained untrained. Behavioural and heart rate responses in a novel object test and 2 handling fear tests (HFTs) were measured. The HFTs were conducted with both an unknown (HFT unknown) and a known handler (HFT-known). RESULTS: There was no effect of the handling procedure on the horses' behavioural and heart rate responses in the novel object test, nor in the HFT-unknown. In the HFT-known, however, handled horses showed a significantly shorter duration of reluctance behaviour compared with controls, whereas heart rates did not differ. Heart rates correlated significantly between tests. CONCLUSIONS: Previous handling may affect the behavioural fear response of horses when handled by their usual handler, whereas this effect did not apply to an unknown handler. Heart rates appeared unaffected by handling and may be a more reliable indicator of fearfulness. Known handlers may 'mask' behavioural responses of horses in fear tests and thus handling by a known handler during testing may not be appropriate for objective evaluation of fearfulness in a practical situation. PMID- 25138592 TI - A theoretical study of the L3 pre-edge XAS in Cu(II) complexes. AB - L2,3 spectra of Cu(II) complexes have been simulated by means of time dependent DFT. Besides the agreement between theory and experiment, the adopted approach provided further insights into the use of the Cu(II) L3-edge intensity and position to investigate the Cu-ligand symmetry-restricted covalency and the ligand-field strength. PMID- 25138591 TI - HIV-1 coreceptor usage in paired plasma RNA and proviral DNA from patients with acute and chronic infection never treated with antiretroviral therapy. AB - Although an independent evolution of viral quasispecies in different body sites might determine a differential compartmentalization of viral variants, the aim of this paper was to establish whether sequences from peripheral blood mononuclear cells (PBMCs) and plasma provide different or complementary information on HIV tropism in patients with acute or chronic infection. Tropism was predicted using genotypic testing combined with geno2pheno (coreceptor) analysis at a 10% false positive rate in paired RNA and DNA samples from 75 antiretroviral-naive patients (divided on the basis of avidity index into patients with a recent or long lasting infection). A high prevalence of R5 HIV strains (97%) was observed in both compartments (plasma and PBMCs) in patients infected recently. By contrast, patients with a long-lasting infection showed a quite different situation in the two compartments, revealing more (46%) X4/DM in PBMCs than patients infected recently (3%) (P = 0.008). As- a knowledge of viral strains in different biological compartments might be crucial to establish a therapeutic protocol, it could be extremely useful to detect not only viral strains in plasma, but also viruses hidden or archived in different cell compartments to better understand disease evolution and treatment efficacy in patients infected with HIV. PMID- 25138594 TI - Planet-satellite nanostructures made to order by RAFT star polymers. AB - The investigation and application of complex nanostructures requires the hierarchical arrangement of distinct domains on a small scale. Herein, we report a method to prepare planet-satellite arrangements using RAFT polymers. Our approach is based on star polymers decorated with trithiocarbonate groups on their outer periphery that attach to gold surfaces and thus provide the polymer with the ability to connect (larger) gold nanoparticle planets with (smaller) gold nanoparticle satellites. By adjusting the molecular weight of the polymeric linker, nanostructures with tailored planet-satellite distances, as evidenced by transmission electron microscopy, are obtained. This strategy offers a straightforward way to prepare gold nanoparticle scaffolds with multiple reactive functionalities at defined distances from the central core. PMID- 25138595 TI - Time efficient way to calculate oxygen transfer areas and power input in cylindrical disposable shaken bioreactors. AB - Disposable orbitally shaken bioreactors are a promising alternative to stirred or wave agitated systems for mammalian and plant cell cultivation, because they provide a homogeneous and well-defined liquid distribution together with a simple and cost-efficient design. Cultivation conditions in the surface-aerated bioreactors are mainly affected by the size of the volumetric oxygen transfer area (a) and the volumetric power input (P/VL ) that both result from the liquid distribution during shaking. Since Computational Fluid Dynamics (CFD)-commonly applied to simulate the liquid distribution in such bioreactors-needs high computing power, this technique is poorly suited to investigate the influence of many different operating conditions in various scales. Thus, the aim of this paper is to introduce a new mathematical model for calculating the values of a and P/VL for liquids with water-like viscosities. The model equations were derived from the balance of centrifugal and gravitational forces exerted during shaking. A good agreement was found among calculated values for a and P/VL , CFD simulation values and empirical results. The newly proposed model enables a time efficient way to calculate the oxygen transfer areas and power input for various shaking frequencies, filling volumes and shaking and reactor diameters. All these parameters can be calculated fast and with little computing power. PMID- 25138596 TI - Spatiotemporal mapping of vascularization and innervation in the fetal murine intestine. AB - BACKGROUND: In mice, the intestinal tube develops from the splanchopleure before embryonic day 9.5. Subsequent patterning of nerves and blood vessels is critical for normal digestive function. A hierarchical branching vascular network allows for efficient nutrient absorption, while the complex enteric nervous system regulates intestinal motility as well as secretion, absorption, and blood flow. Despite the well-recognized significance of these systems, the precise mechanisms by which they develop have not been clearly established in mammals. RESULTS: Using a novel whole-mount immunohistochemical protocol, we visualize the pattern of intestinal neurovascular development in mice between embryonic day 10.5 and birth. In particular, we focus on the development and remodeling of the enteric vascular plexus, the migration and organization of enteric neural crest-derived cells, and the integration of peripheral sympathetic nerves with the enteric nervous system. These correlative data lead us to hypothesize a functional interaction between migrating neural crest-derived cells and endothelial cells of the primary capillary plexus, as well as a subsequent interaction between developing peripheral autonomic nerves and differentiated neural crest-derived cells. CONCLUSIONS: These studies provide useful anatomical data for continuing investigations on the functional mechanisms underlying intestinal organogenesis. PMID- 25138598 TI - Aerobic decolorization and degradation of Acid Orange G (AOG) by suspended growing cells and immobilized cells of a yeast strain Candida tropicalis TL-F1. AB - In this study, aerobic decolorization and degradation of azo dye Acid Orange G (AOG) by both suspended growing cells and immobilized cells of a yeast strain Candida tropicalis TL-F1 were studied. The effects of different parameters on decolorization of AOG by both growing suspended and immobilized strain TL-F1 were investigated. Furthermore, a possible decolorization mechanism of AOG was proposed through analyzing metabolic intermediates using UV-vis and high performance liquid chromatography-mass spectrometry (HPLC-MS) methods. Strain TL F1 could decolorize AOG in both liquid and solid mediums through degradation. The optimal conditions for decolorization with suspended growing cells of strain TL F1 were as follows: 6-10 g/L sucrose, 5-7 g/L urea, >=6 % (v/v) inoculation size, >=160 rpm, 35-40 degrees C, and pH 5.0-6.0; and those for immobilized cells, the conditions were as follows: 4-6 g/L glucose, 0.2-0.4 g/L urea, 6-10 g/L (wet cell pellets) inoculation size, >=160 rpm, 35-40 degrees C, and pH 5.0-7.0. Results of UV-vis scanning spectra suggested that AOG was decolorized through biodegradation, and the possible pathway was proposed through the results of HPLC MS analysis and related literature. This is a systematic research on aerobic decolorization and degradation of AOG by both suspended and immobilized cells of a C. tropicalis strain. PMID- 25138597 TI - Microbial degradation of linseed oil-based elastomer and subsequent accumulation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer. AB - The microbial synthesis of environment-friendly poly(3-hydroxybutyrate--co-3 hydroxyvalerate), PHBV, has been performed by using an alkaliphilic microorganism, Alkaliphilus oremlandii OhILAs strain (GenBank Accession number NR_043674.1), at pH 8 and at a temperature of 30-32 degrees C through the biodegradation of linseed oil-based elastomer. The yield of the copolymer on dry cell weight basis is 90 %. The elastomers used for the biodegradation have been synthesized by cationic polymerization technique. The yield of the PHBV copolymer also varies with the variation of linseed oil content (30-60 %) in the elastomer. Spectroscopic characterization ((1)H NMR and FTIR) of the accumulated product through biodegradation of linseed oil-based elastomers indicates that the accumulated product is a PHBV copolymer consisting of 13.85 mol% of 3 hydroxyvalerate unit. The differential scanning calorimetry (DSC) results indicate a decrease in the melting (T m) and glass transition temperature (T g) of PHBV copolymer with an increase in the content of linseed oil in the elastomer, which is used for the biodegradation. The gel permeation chromatography (GPC) results indicate that the weight average molecular weight (M w) of PHBV copolymer decreases with an increasing concentration of linseed oil in the elastomer. The surface morphology of the elastomer before and after biodegradation is observed under scanning electron microscope (SEM) and atomic force microscope (AFM); these results indicate about porous morphology of the biodegraded elastomer. PMID- 25138599 TI - Crystal structure of Talaromyces cellulolyticus (formerly known as Acremonium cellulolyticus) GH family 11 xylanase. AB - Talaromyces cellulolyticus (formerly known as Acremonium cellulolyticus) is one of the mesophilic fungi that can produce high levels of cellulose-related enzymes and are expected to be used for the degradation of polysaccharide biomass. In silico analysis of the genome sequence of T. cellulolyticus detected seven open reading frames (ORFs) showing homology to xylanases from glycoside hydrolase (GH) family 11. The gene encoding the GH11 xylanase C (TcXylC) with the highest activity was used for overproduction and purification of the recombinant enzyme, permitting solving of the crystal structure to a resolution of 1.98 A. In the asymmetric unit, two kinds of the crystal structures of the xylanase were identified. The main structure of the protein showed a beta-jelly roll structure. We hypothesize that one of the two structures represents the open form and the other shows the close form. The changing of the flexible region between the two structures is presumed to induce and accelerate the enzyme reaction. The specificity of xylanase toward the branched xylan is discussed in the context of this structural data and by comparison with the other published structures of xylanases. PMID- 25138600 TI - Effects of temperature and substrate concentration on lipid production by Chlorella vulgaris from enzymatic hydrolysates of lipid-extracted microalgal biomass residues (LMBRs). AB - The enzymatic hydrolysates of the lipid-extracted microalgal biomass residues (LMBRs) from biodiesel production were evaluated as nutritional sources for the mixotrophic growth of Chlorella vulgaris and lipid production at different temperature levels and substrate concentrations. Both parameters had a significant effect on cell growth and lipid production. It was observed that C. vulgaris could grow mixotrophically in a wide range of temperatures (20~35 degrees C). The optimal temperature for cell growth and lipid accumulation of the mixotrophic growth of C. vulgaris was between 25 and 30 degrees C. The neutral lipids of the culture at 25 degrees C accounted for as much as 82 % of the total lipid content in the microalga at culture day 8. Fatty acid composition analysis showed that the increase of saturated fatty acids was proportional to the increase in temperature. The maximum biomass concentration of 4.83 g/L and the maximum lipid productivity of 164 mg/L/day were obtained at an initial total sugar concentration of 10 g/L and an initial total concentration of amino acids of 1.0 g/L but decreased at lower and higher substrate concentrations. The present results show that LMBRS could be utilized by the mixotrophic growth of C. vulgaris for microalgal lipid production under the optimum temperature and substrate concentration. PMID- 25138601 TI - Optimizing cultivation strategies for robust algal growth and consequent removal of inorganic nutrients in pretreated livestock effluent. AB - Dilution was employed as a pretreatment strategy to increase light transmittance and decrease ammonia toxicity in piggery effluent prior to the cultivation of microalgae. The dilution effect was quantitatively determined based on both the maximum specific nutrient consumption rate and the maximum growth coefficient to minimize the usage of diluent. The biomass productivity of microalgae was also evaluated to select the best species among the five different candidates examined. A 20-fold dilution of piggery wastewater resulted in decreased chromaticity (584 mg Pt-Co L(-1)) and total nitrogen (76 mg L(-1)), on which the microalgae cultivation was more effective for an algal growth compared to the other dilution factors. If the initial cell concentration of Scenedesmus quadricauda increased, the production of biomass tended to improve. Robust growth and harvesting of S. quadricauda were achieved, and the associated consistent removal of inorganic nutrients was accomplished during the semi-continuous cultivation of the best species. PMID- 25138602 TI - Preface. PMID- 25138603 TI - Disseminated cysticercosis revealed by subcutaneous nodules in a migrant from Cameroon. PMID- 25138604 TI - Twin-reversed arterial perfusion sequence in a triple monochorionic pregnancy with two direct pump fetuses results in significant cyclic Doppler waveform. AB - We report a case of a twin-reversed arterial perfusion (TRAP) sequence complication in monochorionic triplets, in which both normal fetuses were directly connected to the umbilical cord of the acardiac fetus, thus both acting as a pump twin. Doppler ultrasound showed a significant waveform pattern with two superposed systolic waveforms in the same vessel. After birth, placental findings confirmed the existence of two direct pump twins. The Doppler pattern described here may be of help to distinguish the existence of two pump twins in a triplet monochorionic pregnancy with TRAP. PMID- 25138605 TI - Spironolactone in the treatment of central serous chorioretinopathy - a case series. AB - BACKGROUND: The pathogenesis of central serous chorioretinopathy (CSC) is still poorly understood. An animal model of CSC proved that the mineralocorticoid receptor [1] of the choroid also plays a role in CSC. Since there is still no evidence-based therapy for non-self-limiting CSC, this case series evaluates the effect of oral spironolactone in CSC patients. METHODS: In this interventional, uncontrolled, prospective case series, we present 18 consecutive CSC patients. Patients were treated with spironolactone 25 mg twice daily (Spironolacton AL(r) 50 mg, ALIUD PHARMA) for up to 12 weeks. Follow-up examinations with BCVA, OCT, and EDI-OCT were performed at 1, 2, and 3 months after starting the treatment. Main outcome measure was a change of subretinal fluid (SRF) (in micrometers) measured by optical coherence tomography. Secondary outcome was a change in central retinal thickness (CRT) (in micrometers) measured by OCT and a change in BCVA. RESULTS: The subretinal fluid (SRF; mean) decreased from 219 MUm (baseline) to 100 MUm (visit 3) (difference 119 MUm). Total central retinal thickness (CRT; mean) decreased from 405 MUm before treatment (baseline) to 287 MUm after treatment (difference 118 MUm). The BCVA (in logMAR; mean) increased from 0.32 at baseline to 0.20 at visit 3. CONCLUSION: Our case series could confirm a positive influence of spironolactone on the course CSC. Longer follow-up with a larger number of cases could provide more data about the long-term efficiency, recurrences, and safety of this well-tolerated and non-invasive treatment option of CSC. PMID- 25138606 TI - Cytomegalovirus anterior uveitis: long-term follow-up of immunocompetent patients. AB - BACKGROUND: We aimed to report on the clinical findings and long-term prognosis of patients with cytomegalovirus (CMV) anterior uveitis. METHODS: This was a retrospective observational study on 15 immunocompetent patients with CMV anterior uveitis and a follow-up longer than 24 months (mean: 62.1 +/- 28.5 months). RESULTS: Uveitis was unilateral and hypertensive in all cases, with acute relapsing having the characteristics of Posner-Schlossman syndrome in nine (60 %) and chronic in nine patients (40 %), three of whom were clinically classified as Fuchs' heterocromic iridocyclitis (20 %). All patients received topical antiviral and corticosteroid therapy, with six patients also receiving systemic therapy with valganciclovir or acyclovir. The mean number of uveitis relapses significantly decreased, before and after anti-CMV therapy, from 0.23 +/ 0.17 to 0.03 +/- 0.03 (p < 0.001), without significant differences among patients treated with topical therapy alone or combined topical and systemic therapy. Cataracts developed in nine out of 13 patients (69.2 %). A chronic raise in intraocular pressure (IOP) was found in 13 patients (86.6 %), with nine requiring surgery (60 %). At the end of the follow-up, all patients had a quiescent uveitis, with ten of them requiring topical low dose steroid therapy (66.6 %) and combined with systemic acyclovir in four cases. Eight patients (53.3 %) were on antiglaucomatous therapy. The last mean IOP value was 14.9 +/- 3.6 mmHg (range 8-21 mmHg), and visual acuity was 0.89 +/- 0.21. CONCLUSIONS: CMV associated anterior uveitis has a fairly good long-term visual prognosis. Antiviral therapy can reduce the frequency of relapses, but cataracts and a chronic raise in IOP are frequent complications often requiring a surgical approach. PMID- 25138608 TI - Aberrant drug-related behaviors: a qualitative analysis of medical record documentation in patients referred to an HIV/chronic pain clinic. AB - BACKGROUND: Due to rising rates of opioid addiction and overdose among individuals on chronic opioid therapy, aberrant drug-related behaviors (ADRBs) are an important and challenging issue. Our objective was to qualitatively investigate the documentation of ADRBs in the medical record. METHODS: Manually abstracted provider notes from an HIV primary care clinic were analyzed using content analysis methods. RESULTS: Categories of ADRBs identified included patients requesting opioids, obtaining nonprescribed opioids, and becoming emotional about opioids. We also identified several types of provider language used when documenting ADRBs, including purely descriptive language and emotional language such as labeling, frustration, and concern, and responses such as setting conditions for opioid prescription and action-oriented language. CONCLUSIONS: The impact of including emotional language in the medical record is unknown. Development of instruments that can be used to facilitate ADRB documentation, as well as evidence-based approaches to addressing ADRBs, is needed. PMID- 25138609 TI - Cutaneous manifestations of methotrexate-associated lymphoproliferative disorders: report of two cases and a review of the literature. PMID- 25138610 TI - Heart failure as a risk factor for diabetes mellitus. AB - BACKGROUND: Diabetes mellitus (DM) is a well-recognized risk factor for heart failure (HF). We hypothesized that HF also increases the risk for DM. OBJECTIVE: We explored the hypothesis that HF is a risk factor for DM. METHODS: The Cardiovascular Health Study was a prospective cohort study of cardiovascular risk in ambulatory older adults. We used a limited-access dataset provided by the National Heart, Lung and Blood Institute. The impact of HF at baseline on DM after 3 or 4 years was examined in a cohort of 3,748 nondiabetic participants aged >=65 years. The magnitude and significance of the association were evaluated using logistic regression models. Analyses were performed with and without adjustment for confounders and separately among subjects with normal and impaired fasting glucose at baseline. RESULTS: Among subjects with normal fasting glucose at baseline, HF significantly increased the odds of developing impaired fasting glucose after 3 or 4 years [odds ratio (OR) 2.18, 95% confidence interval (CI) 1.03-4.61, p = 0.043] or overt DM (OR 4.78, 95% CI 1.84-12.4, p < 0.001). After adjusting for demographic and biomedical factors, HF remained significantly associated with a worsening DM status (OR 2.43, 95% CI 1.38-4.29, p = 0.002). CONCLUSIONS: In the elderly population, the presence of HF more than doubles the incidence of DM within a few years. This association remains significant when adjusting for age, gender and cardiovascular comorbidities. PMID- 25138607 TI - Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity. AB - Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m(2) +/- 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA (miR)-29a; promoter region hypomethylation of nuclear receptor factor (NRF1) and fatty acid transporter (SLC27A4), and hypermethylation of fatty acid synthase, and to exon hypomethylation of 6-phosphofructo-2-kinase and Ser/Thr protein kinase. Directional change in the endurance networks was validated by lower intramyocellular lipid, increased capillarity, GLUT4, hexokinase, and mitochondrial enzyme activity and proteome. Resistance training also lowered lipid and increased enzyme activity and caused GLUT4 promoter hypomethylation; however, training was inconsequential to GLUT4, capillarity, and metabolic transcriptome. miR-195 connected to negative regulation of vascular development. To conclude, integrated molecular network modelling revealed differential DNA methylation and miRNA expression changes occur in skeletal muscle in response to chronic exercise training that are most pronounced with endurance training and topographically associated with functional metabolic and microvascular plasticity relevant to diabetes rehabilitation. PMID- 25138611 TI - Comparison of the long-term skeletal stability between a biodegradable and a titanium fixation system following BSSO advancement - a cohort study based on a multicenter randomised controlled trial. AB - Biodegradable fixation systems could reduce or eliminate the problems associated with removal of titanium plates. A multicenter randomised controlled trial (RCT) was performed in the Netherlands from December 2006-July 2009, and originally 230 injured and orthognathic patients were included. The patients were randomly assigned to either a titanium control group (KLS Martin) or to a biodegradable test group (Inion CPS). The aim of the present study was to compare the long-term skeletal stability of advancement bilateral sagittal split osteotomies (BSSO) of a biodegradable system and a titanium system. Only patients from the original RCT who were at least 18 years old and who had a BSSO advancement osteotomy were included. Those who had simultaneous Le Fort I osteotomy or genioplasty were excluded. Analysis of skeletal stability was made by digital tracing of lateral cephalograms. Long-term skeletal stability in BSSO advancement did not differ significantly between patients treated with biodegradable plates and screws and those treated with titanium plates and screws. Given the comparable amount of relapse, the general use of Inion CPS in the treatment of BSSO advancement should not be discouraged. On the basis of other properties a total picture of the clinical use can be obtained; the short-term stability, the intraoperative switches, the number of plates removed and cost-effectiveness. Trial registration of original RCT: http://www.controlled-trials.com; ISRCTN 44212338. PMID- 25138612 TI - Biomechanical investigation of naso-orbitoethmoid trauma by finite element analysis. AB - Naso-orbitoethmoid fractures account for 5% of all facial fractures. We used data derived from a white 34-year-old man to make a transient dynamic finite element model, which consisted of about 740 000 elements, to simulate fist-like impacts to this anatomically complex area. Finite element analysis showed a pattern of von Mises stresses beyond the yield criterion of bone that corresponded with fractures commonly seen clinically. Finite element models can be used to simulate injuries to the human skull, and provide information about the pathogenesis of different types of fracture. PMID- 25138613 TI - Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate related osteonecrosis of the jaw: a prospective feasibility study. AB - Our aim was to assess the feasibility of using leucocyte-rich and platelet-rich fibrin (L-PRF) for the treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a single group study. After treatment with L-PRF, the response of each patient was recorded 1 month and 4 months postoperatively. Further assessments were made of the site, stage, concentration of c-terminal crosslinked telopepide of type 1 collagen, and actinomycosis. Among the total of 34 patients, 26 (77%) showed complete resolution, 6 (18%) had delayed resolution, and 2 (6%) showed no resolution. There was a significant association between the response to treatment and the stage of BRONJ (p=0.002) but no other significant associations were detected. This study has shown that it is feasible to use L-PRF for the treatment of BRONJ, but the effectiveness cannot be judged with this study design. Randomised prospective trials are needed to confirm this. PMID- 25138614 TI - Knee arthrodesis as limb salvage for complex failures of total knee arthroplasty. AB - Patients with multiple failures of total knee arthroplasty (TKA) are challenging limb salvage cases. Twenty one patients over the last 10 years were referred to our service for knee fusion by arthroplasty surgeons who felt they were not candidates for revision TKA. Active infection was present in 76.2% and total bone loss averaged 6.6 cm. Lengthening was performed in 7/22 patients. Total time in Ilizarov frames was 9 months, with 93.3% union. Patients treated with IM fusion nails had 100% union. Average LLD increased from 3.6 to 4.5 cm following intervention, while those with concurrent lengthening improved to 1.6 cm. Findings suggest that bone loss and the soft-tissue envelope dictate knee fusion method, and multiple techniques may be needed. A treatment algorithm is presented. PMID- 25138615 TI - Relationship between mechanical axis-derived and anatomic landmark-derived femoral rotation in TKA: a three-dimensional CT study. AB - We sought to determine the relationship between the mechanical axis-derived and the anatomic landmark-derived femoral rotational axes using three dimensional computed tomographic images of 20 lower extremities. The mechanical axis-derived femoral rotational axis was created on the distal articular surface of the femur using coronal mechanical limb axis and the reconstructed images of the femur. Then, we measured the angular difference between mechanical axis-derived and anatomic landmark-derived femoral rotational axes. The mechanical axis-derived femoral rotational axis was externally rotated with a mean of 2.2 degrees (range, 0 to 4.7 degrees ; SD, 1.0) compared with the surgical epicondylar axis. Our findings should be considered to obtain a proper femoral rotational axis in total knee arthroplasty. PMID- 25138617 TI - Shame if you do--shame if you don't: women's experiences of infant feeding. AB - Emotions such as guilt and blame are frequently reported by non-breastfeeding mothers, and fear and humiliation are experienced by breastfeeding mothers when feeding in a public context. In this paper, we present new insights into how shame-related affects, cognitions and actions are evident within breastfeeding and non-breastfeeding women's narratives of their experiences. As part of an evaluation study of the implementation of the UNICEF UK Baby Friendly Initiative Community Award within two primary (community based) care trusts in North West England, 63 women with varied infant feeding experiences took part in either a focus group or an individual semi-structured interview to explore their experiences, opinions and perceptions of infant feeding. Using a framework analysis approach and drawing on Lazare's categories of shame, we consider how the nature of the event (infant feeding) and the vulnerability of the individual (mother) interact in the social context to create shame responses in some breastfeeding and non-breastfeeding mothers. Three key themes illustrate how shame is experienced and internalised through 'exposure of women's bodies and infant feeding methods', 'undermining and insufficient support' and 'perceptions of inadequate mothering'. The findings of this paper highlight how breastfeeding and non-breastfeeding women may experience judgement and condemnation in interactions with health professionals as well as within community contexts, leading to feelings of failure, inadequacy and isolation. There is a need for strategies and support that address personal, cultural, ideological and structural constraints of infant feeding. PMID- 25138618 TI - Exploring the myths of morphine in cancer: views of the general practice population. AB - BACKGROUND: Morphine is widely used in cancer care, and understanding the concerns and perceptions of patients, family and friends is vital to managing pain and distress effectively. The 'myths of morphine' have frequently been discussed in medical literature, yet the extent to which such views are held is not clear. This qualitative project explores the perceptions and attitudes of the wider community towards morphine use in cancer care, to understand this 'mythology' according to those who in the future may themselves require its use. METHODS: Semi-structured interviews were held with patients presenting to a metropolitan general practice clinic in Melbourne, Australia. A grounded theory framework underpinned the data collection and thematic analysis undertaken. RESULTS: Interviewees (15) were aged 24-81, with a variety of experiences with cancer care and previous morphine use. Interviewees were highly supportive of morphine use in cancer care, with this attitude founded on the perceived severity of cancer pain and the powerful nature of morphine. They described a number of reasons morphine may be used in cancer care: to treat pain, to enable peace and also as a treatment for cancer. CONCLUSION: The public view of morphine to emerge from this study is markedly different from that discussed in the myths of morphine. It is viewed as a medication that has the ability to provide peace and control both pain and the course of cancer. The participants in this study described a wish for greater involvement in pain control decisions, perceiving morphine as a facilitator rather than a barrier to good cancer care. PMID- 25138619 TI - 'Prostate Abscess' as the Initial Manifestation of Granulomatosis with Polyangiitis (Wegener's Granulomatosis). AB - Prostatic involvement in granulomatosis with polyangiitis (GWP), formerly known as Wegener's granulomatosis, is rare, mostly arising in the context of systemic involvement. Prostatic involvement as the first manifestation of this systemic disease is exceptionally rare. We hereby present the case of a 41-year-old male patient who underwent transurethral prostate resection for what was initially diagnosed as suppurative, focally necrotizing prostatitis. Prolonged postoperative fever that did not respond to various treatments, as well as the subsequent appearance of a left pleural effusion, a left upper pulmonary lobe lesion and cutaneous nodules, led to a reevaluation of histological slides which, along with the determination of serum c-ANCA/anti-PR3 antibody levels, established the diagnosis of GWP. Physicians, and especially urologists and infectious diseases specialists, should be aware of this rare association and consider GWP in the event of nonresolving prostatitis, especially when characteristic symptoms from other systems appear. PMID- 25138616 TI - A systematic review of the quality of reporting in published smoking cessation trials for pregnant women: an explanation for the evidence-practice gap? AB - BACKGROUND: To facilitate translation of evidence into clinical practice, it is critical that clear, specific, and detailed information about interventions is provided in publications to promote replication, appropriate aggregation in meta analysis, and implementation. This study examined whether twenty elements of interventions deemed essential for such translational application were reported in sufficient detail in smoking cessation trials with pregnant women. METHODS: Searches of electronic databases using MeSH terms and keywords identified peer reviewed English language studies published between 2001 and 2012. Eligible studies reported a smoking cessation intervention targeted at pregnant women and met Cochrane's Effective Practice and Organization of Care group study design criteria. Each intervention arm of eligible studies was assessed against the developed twenty criteria. RESULTS: Thirty relevant studies reported the findings of 45 intervention arms. The mode of delivery of the intervention was reported in 100% of intervention arms. Other well-reported criteria included reporting of the provider who delivered the intervention (96%), sample characteristics (80%), and the intervention setting (80%). Criteria not reported adequately included care provided to women who relapse (96% not reported), details about training given to providers (77% not reported), and the method of quit advice advised (76% not reported). No studies reported 100% of relevant criteria. CONCLUSIONS: Current standards of reporting of intervention content and implementation are suboptimal. The use of smoking cessation specific checklists for reporting of trials, standard reporting using behaviour change taxonomies, and the publication of protocols as supplements should be considered as ways of improving the specificity of reporting. PMID- 25138620 TI - An international consensus algorithm for management of chronic postoperative inguinal pain. AB - PURPOSE: Tension-free mesh repair of inguinal hernia has led to uniformly low recurrence rates. Morbidity associated with this operation is mainly related to chronic pain. No consensus guidelines exist for the management of this condition. The goal of this study is to design an expert-based algorithm for diagnostic and therapeutic management of chronic inguinal postoperative pain (CPIP). METHODS: A group of surgeons considered experts on inguinal hernia surgery was solicited to develop the algorithm. Consensus regarding each step of an algorithm proposed by the authors was sought by means of the Delphi method leading to a revised expert based algorithm. RESULTS: With the input of 28 international experts, an algorithm for a stepwise approach for management of CPIP was created. 26 participants accepted the final algorithm as a consensus model. One participant could not agree with the final concept. One expert did not respond during the final phase. CONCLUSION: There is a need for guidelines with regard to management of CPIP. This algorithm can serve as a guide with regard to the diagnosis, management, and treatment of these patients and improve clinical outcomes. If an expectative phase of a few months has passed without any amelioration of CPIP, a multidisciplinary approach is indicated and a pain management team should be consulted. Pharmacologic, behavioral, and interventional modalities including nerve blocks are essential. If conservative measures fail and surgery is considered, triple neurectomy, correction for recurrence with or without neurectomy, and meshoma removal if indicated should be performed. Surgeons less experienced with remedial operations for CPIP should not hesitate to refer their patients to dedicated hernia surgeons. PMID- 25138621 TI - Secondary inguinal hydatidosis mimicking irreducible inguinal hernia: report of a rare case. AB - Peritoneal hydatidosis secondary to liver hydatid disease is not uncommon but peritoneal hydatidosis herniating to the inguinal canal is rare, with fewer than five cases reported in the literature. We describe a 54-year-old man who presented with a progressively enlarging soft, cystic swelling in the right inguinal region. Clinical examination suggestive of irreducible right inguinal hernia and ultrasonography revealed it to be a cystic swelling within the hernial sac. The swelling was excised en bloc and open mesh hernioplasty was performed. Cyst biopsy revealed hydatid disease; hence, the patient was put on adjunctive albendazole chemotherapy for 3 months. PMID- 25138622 TI - Ultrasound scoring in combination with ultrasound elastography for differentiating benign and malignant thyroid nodules. AB - OBJECTIVE: The aim of this study was to evaluate the value of ultrasound scores obtained by conventional ultrasonography and ultrasound elastography in the differentiation of benign and malignant thyroid nodules in Chinese patients. METHODS: This study included 297 patients who were referred for surgery for compressive symptoms or suspicion of malignancy. Five hundred and twelve thyroid nodules were examined by ultrasonography. The final diagnosis was based on histological findings. A seven-point ultrasound scoring system based on conventional ultrasonography and a five-point scoring system based on ultrasound elastography were applied independently or in combination. The receiver operating characteristic (ROC) curves were graphed, and the areas under the curves (AUCs) were compared using the chi(2) -test. RESULTS: Solid composition, hypo-echoic appearance, an irregular or blurred margin, an aspect ratio >=1, intranodular blood flow and presence of microcalcifications were significant predictors of malignant thyroid nodules. The AUC (95% CI) was 0.9067 (0.8817-0.9318) for the ultrasound scores based on conventional ultrasonography and 0.9080 (0.8842 0.9317) for the elasticity scores. The combination of these two scoring systems provided good accuracy with an AUC (95% CI) of 0.9415 (0.9223-0.9606), which was significantly higher than that obtained with the conventional ultrasound scores (chi(2) = 36.03, P < 0.001) or the elasticity scores (chi(2) = 12.80, P < 0.001) individually. When we set the cut-point to >=5, the sensitivity and specificity were 85.22% and 87.38%, respectively. CONCLUSIONS: Elastography in combination with conventional ultrasonography is a promising imaging-based approach that can assist in the differential diagnosis of thyroid cancer. PMID- 25138624 TI - Evaluation of elastic bands for lower extremity resistance training in adults with and without musculo-skeletal pain. AB - Therapists commonly use elastic bands in resistance exercises during rehabilitation of smaller muscles, such as in the shoulder. However, the effectiveness has not yet been investigated for larger muscle groups. This study investigates muscle activity during lower extremity exercises. Electromyographic (EMG) activity of 10 muscles was measured in 24 women and 18 men during lunges with elastic resistance, lunges with dumbbells, and unilateral leg press in machine using 10 repetition maximum loadings, and normalized to maximal voluntary isometric contraction EMG. Lunges with dumbbells and leg press showed higher activity than lunges with elastic resistance for the vasti and rectus femoris (P < 0.01), whereas lunges with elastic resistance showed higher activity of gluteus maximus, hamstrings, and erector spinae (P < 0.01). Gender, age, and pain in the knees and hip did not influence these findings. However, pain in the lower back decreased muscular activity of the gluteus maximus and vastus medialis (P < 0.01). Lunges with elastic resistance induce high levels of muscle activity in all the large muscle groups at the hip, knee, and back. Importantly, the efficiency of these exercises was equally high regardless of gender, age, and pain in the knees and hip, whereas pain in the lower back led to altered activation strategies. PMID- 25138625 TI - Effects of garlic extract on spreading depression: In vitro and in vivo investigations. AB - OBJECTIVES: The potential use of garlic for prevention and treatment of different types of headaches has been suggested by several medieval literatures. Cortical spreading depression (CSD), a propagating wave of neuroglial depolarization, was established as a target for anti-migraine drugs. This study was designed to investigate the effect of garlic extract on CSD in adult rats. METHODS: CSD was induced by KCl microinjection in the somatosensory cortex. The effects of five different concentrations of garlic oil (1-500 MUl/l) were tested on different characteristic features of CSD in necocortical slices. In in vivo experiments, the effects of garlic oil on electrophysiological and morphological changes induced by CSD were investigated. RESULTS: Garlic oil in a dose-dependent manner decreased the amplitude of CSD but not its duration and velocity in neocortical brain slices. Garlic oil at concentration of 500 MUl/l reversibly reduced the amplitude of the field excitatory post-synaptic potentials and inhibited induction of long-term potentiation in the third layer of neocortical slices. In in vivo studies, systemic application of garlic oil (1 ml/l) for three consecutive days reduced the amplitude and repetition rate of CSD. Garlic oil also prevented of CSD-induced reactive astrocytosis in the neocortex. DISCUSSION: Garlic oil suppresses CSD, likely via inhibition of synaptic plasticity, and prevents its harmful effects on astrocyte. Further studies are required to identify the exact active ingredient(s) of garlic oil that inhibit CSD and may have the potential to use in treatment of CSD-related disorders. PMID- 25138626 TI - "There is iron and iron..." Burkinabe women's perceptions of iron supplementation: a qualitative study. AB - Most pregnant women in Burkina Faso are iron deficient and many are anemic. This study assessed women's understanding of anemia and the role of iron in preventing and treating this condition. A qualitative study was conducted within a randomized controlled trial of weekly iron supplementation in a rural malaria endemic area. Focus groups with women of similar age, parity, and marital status took place in 12 of 24 study villages. Two additional focus groups were conducted with female field workers. Tape-recorded transcripts were translated into French and analyzed using Framework analysis. Anemia, for which no Moore term or traditional treatment for anemia was evident, was described in terms of blood volume. Moderate blood loss (diminished blood) could be easily replaced by eating well and was not considered serious. Massive blood loss (finished blood) was a rare, life-threatening illness. Iron tablets could increase blood volume and help women withstand massive blood loss at delivery, but for the latter, transfusion was indicated. Women had no knowledge of iron's role and did not readily concede that iron supplements contained elemental iron. Neither adolescents nor field workers were convinced of the benefits of supplementing non-pregnant adolescents, who were incorrectly considered to be at low risk of anemia. Young women's knowledge of anemia did not provide an adequate explanatory framework to motivate anemia prevention. Improving information on the role of iron is especially important for adolescent girls who may be incorrectly considered at low risk of anemia as they have not yet experienced pregnancy. PMID- 25138627 TI - Bone density among infants of gestational diabetic mothers and macrosomic neonates. AB - Decreased bone density has been found among infants of diabetic mothers and among large-for-gestational-age newborns. To evaluate which etiologies (physical or metabolic effect) have the greatest impact on neonatal bone density. A case control study was conducted that included two study groups: one comprising 20 appropriate-for-gestational-age (AGA) infants of gestational diabetic mothers (IGDM) and matched controls, and the other comprising 20 macrosomic infants (birth weight > 4 kg) and matched controls. Bone density was examined along the tibia bone using quantitative ultrasound that measured speed of sound. Bone density among the group of macrosomic infants was significantly lower than among the control group (2,976 vs. 3,120 m/s respectively, p < 0.005). No differences in bone density were found between infants of diabetic mothers and their controls (3,005 vs. 3,043 m/s respectively, p = 0.286). Low bone density was predicted only by birth weight (for every increase of 100 g) (OR 1.148 [CI 1.014-1.299], p = 0.003). Bone density was found to be low among macrosomic newborn infants, whereas among AGA-IGDM infants bone density was similar to that of the control group. These findings strengthen the hypothesis that reduced fetal movements secondary to fetal macrosomia constitute the mechanism for reduced bone density. PMID- 25138628 TI - Pathways community care coordination in low birth weight prevention. AB - The evidence is limited on the effectiveness of home visiting care coordination in addressing poor birth outcome, including low birth weight (LBW). The Community Health Access Project (CHAP) utilizes community health workers (CHWs) to identify women at risk of having poor birth outcomes, connect them to health and social services, and track each identified health or social issue to a measurable completion. CHWs are trained individuals from the same highest risk communities. The CHAP Pathways Model is used to track each maternal health and social service need to resolution and CHWs are paid based upon outcomes. We evaluated the impact of the CHAP Pathways program on LBW in an urban Ohio community. Women participating in CHAP and having a live birth in 2001 through 2004 constituted the intervention group. Using birth certificate records, each CHAP birth was matched through propensity score to a control birth from the same census tract and year. Logistic regression was used to examine the association of CHAP participation with LBW while controlling for risk factors for LBW. We identified 115 CHAP clients and 115 control births. Among the intervention group there were seven LBW births (6.1 %) compared with 15 (13.0 %) among non-CHAP clients. The adjusted odds ratio for LBW was 0.35 (95 % confidence interval, 0.12-0.96) among CHAP clients. This study provides evidence that structured community care coordination coupled with tracking and payment for outcomes may reduce LBW birth among high-risk women. PMID- 25138629 TI - New evidence on breastfeeding and postpartum depression: the importance of understanding women's intentions. AB - This study aimed to identify the causal effect of breastfeeding on postpartum depression (PPD), using data on mothers from a British survey, the Avon Longitudinal Study of Parents and Children. Multivariate linear and logistic regressions were performed to investigate the effects of breastfeeding on mothers' mental health measured at 8 weeks, 8, 21 and 32 months postpartum. The estimated effect of breastfeeding on PPD differed according to whether women had planned to breastfeed their babies, and by whether they had shown signs of depression during pregnancy. For mothers who were not depressed during pregnancy, the lowest risk of PPD was found among women who had planned to breastfeed, and who had actually breastfed their babies, while the highest risk was found among women who had planned to breastfeed and had not gone on to breastfeed. We conclude that the effect of breastfeeding on maternal depression is extremely heterogeneous, being mediated both by breastfeeding intentions during pregnancy and by mothers' mental health during pregnancy. Our results underline the importance of providing expert breastfeeding support to women who want to breastfeed; but also, of providing compassionate support for women who had intended to breastfeed, but who find themselves unable to. PMID- 25138630 TI - Stiffness versus prestress relationship at subcellular length scale. AB - Local intracellular variations of cell mechanical properties, which are essential for vital cellular functions, have not been well characterized and are poorly understood. Here, we used results from our previous biomechanical imaging study to obtain relationships between intracellular shear modulus and prestress. We found that the subcellular shear modulus vs. prestress relationships exhibited positive linear correlations, consistent with previously observed behaviors at the whole cell and tissue levels. This, in turn, suggests that the prestress may be a unifying factor that determines material properties of living matter at different length scales. PMID- 25138632 TI - Intoxication by angel's trumpet: case report and literature review. AB - BACKGROUND: Brugmansia, commonly referred to as angel's trumpet (AT), has been become popular in Korea as an ornamental shrub. However, it is not generally known by the public that this plant contains tropane alkaloids, and that ingestion of AT can lead to anticholinergic poisoning. CASE PRESENTATION: A 64 year-old Korean female presented with acute mental changes caused by inadvertent ingestion of the petals of AT flowers used as a garnish in a traditional Korean food (bibimbop). She regained her usual level of awareness after 10 hours. CONCLUSION: Considering its easy availability, the toxicity of AT should be addressed to prevent accidental and intentional poisoning by this ornamental plant. PMID- 25138631 TI - Partial gravity unloading inhibits bone healing responses in a large animal model. AB - The reduction in mechanical loading associated with space travel results in dramatic decreases in the bone mineral density (BMD) and mechanical strength of skeletal tissue resulting in increased fracture risk during spaceflight missions. Previous rodent studies have highlighted distinct bone healing differences in animals in gravitational environments versus those during spaceflight. While these data have demonstrated that microgravity has deleterious effects on fracture healing, the direct translation of these results to human skeletal repair remains problematic due to substantial differences between rodent and human bone. Thus, the objective of this study was to investigate the effects of partial gravitational unloading on long-bone fracture healing in a previously developed large animal Haversian bone model. In vivo measurements demonstrated significantly higher orthopedic plate strains (i.e. load burden) in the Partial Unloading (PU) Group as compared to the Full Loading (FL) Group following the 28 day healing period due to inhibited healing in the reduced loading environment. DEXA BMD in the metatarsus of the PU Group decreased 17.6% (p<0.01) at the time of the ostectomy surgery. Four-point bending stiffness of the PU Group was 4.4 times lower than that of the FL Group (p<0.01), while uCT and histomorphometry demonstrated reduced periosteal callus area (p<0.05), mineralizing surface (p<0.05), mineral apposition rate (p<0.001), bone formation rate (p<0.001), and periosteal/endosteal osteoblast numbers (p<0.001/p<0.01, respectively) as well as increased periosteal osteoclast number (p<0.05). These data provide strong evidence that the mechanical environment dramatically affects the fracture healing cascade, and likely has a negative impact on Haversian system healing during spaceflight. PMID- 25138633 TI - Initial influence of right versus left lateral recumbency on the radiographic finding of duodenal gas on subsequent survey ventrodorsal projections of the canine abdomen. AB - Identification of the duodenum and potential abnormalities on survey abdominal radiographs is often difficult unless it contains gas. This study investigated the effect of patient positioning on the presence of duodenal gas in survey abdominal radiographs. One hundred dogs receiving a three-view survey abdominal radiographic study were enrolled in a prospective, randomized study where all dogs were divided into two groups. Group A (n = 51) dogs had a left lateral projection first, followed by a ventrodorsal projection, ending with a right lateral projection. Group B (n = 49) dogs had a right lateral projection first, followed by a ventrodorsal projection, ending with a left lateral projection. The presence of gas within the duodenum and level of distribution of gas throughout the duodenum were recorded for all three projections. In addition, the presence or absence of duodenal pseudoulcers was evaluated on all three projections for each dog. The results for the two groups were compared using Chi-square analysis with a P-value of less than 0.05 being considered significant. Results showed that dogs first placed in left lateral recumbency were significantly more likely to have duodenal gas on the subsequent ventrodorsal and right lateral radiographic projections compared to dogs first placed in right lateral recumbency (P-value < 0.0001). Pseudoulcers were seen in 11 dogs that had duodenal gas making the visualization of pseudoulcers on survey abdominal radiographs somewhat commonplace. This study emphasizes the benefit of using initial left lateral abdominal projections prior to other views for subsequent evaluation of the duodenum. PMID- 25138634 TI - Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes. AB - 20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can inhibit proliferation and promote differentiation of a range of cells, and has anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause toxic hypercalcemia at high doses and is therefore a good candidate for therapeutic use to treat hyperproliferative and autoimmune disorders. In this study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3. The two major products were identified from authentic standards as 20,24 dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3]. The reactions for synthesis of these two products from 20(OH)D3 displayed similar Km values suggesting that they were catalyzed by the same cytochrome P450. Some minor metabolites were produced by reactions with higher Km values for 20(OH)D3. Some metabolites gave mass spectra suggesting that they were the result of hydroxylation followed by dehydrogenation. One product had an increase in the wavelength for maximum absorbance from 263nm seen for 20(OH)D3, to 290nm, suggesting a new double bond was interacting with the vitamin D-triene chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both previously been shown to have higher potency for inhibition of colony formation by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by mouse liver microsomes can generate products with enhanced activity. PMID- 25138635 TI - Corpora lutea of pregnant and pseudopregnant domestic cats reveal similar steroidogenic capacities during the luteal life span. AB - In domestic cats, luteal phases of pregnancy and pseudopregnancy (non-pregnant luteal phase) differ in the course and level of plasma progesterone (P4). Therefore, we assumed differences in luteal steroidogenic capacities. Here we present a comprehensive analysis of intraluteal steroid biogenesis in the domestic cat. We quantitatively measured relative mRNA levels of steroidogenic acute regulatory protein (STAR), cytochrome P450 oxidases (CYP), hydroxysteroid dehydrogenases (HSD), steroid reductase (SRD) and enzymes involved in sulfoconjugation of steroids, i.e. sulfotransferase (SULT) and sulfatase (STS). Protein expression was analysed by Western Blot for HSD3B. Additionally, intraluteal steroid contents were determined. During the pseudopregnant luteal phase, expression of STAR (p=0.005), HSD3B1 (p<0.0001), CYP19A1 (p<0.0001) and HSD17B7 (p=0.008) decreased from formation of the corpus luteum (CL) onwards. HSD3B protein expression was highest in the development/maintenance stage of CL and declined during the subsequent luteal phase of pregnancy and pseudopregnancy. This was in accordance with decreasing intraluteal levels of P4, oestrogens and androgens. In contrast, expression of SRD5A1 (p<0.001) increased with progression through stages of the pseudopregnant CL, being indicative of P4 metabolism via an alternate pathway to dihydrotestosterone (DHT). Compared to the formation stage, expression of SULT1E1 was higher in all other luteal stages of pseudopregnancy (p=0.004), implying a potential sulfoconjugation of oestrogens. Expression of CYP11A1 and CYP17A1 was unaffected by the luteal stage (p>0.05), suggesting a permanent capacity of cat CL to convert progestogens via androgen and oestrogen pathways. In general, mRNA expression profiles of steroidogenic enzymes during the pregnant luteal phase reflected the pseudopregnancy profiles. Intraluteal oestrogen (p<0.0001) and androgen (p=0.008) levels were higher in the formation stage compared to the following luteal stages of pseudopregnancy. Concentrations of P4 were higher in the development/maintenance compared to the regression stages (p=0.01). We conclude that cat CL of the same histomorphological stage are characterised by identical steroidogenic capacities independently of an on-going pregnancy. PMID- 25138636 TI - Zinc oxide nanoparticles induced oxidative stress in mouse bone marrow mesenchymal stem cells. AB - Engineered nanoparticles are developed for various applications in industrial, electrical, agricultural, pharmaceutical and medical fields due to their unique properties. Nanoparticles such as TiO(2) and ZnO are widely used in cosmetics for UV protection. The toxicological investigations of ZnO NPs are highly recommended because of the increasing use in various industrial and consumer products. The toxic potential of ZnO NPs was assumed to be caused by the release of free Zn+ ions in the medium. Many of the in vivo studies suggest the toxic nature of ZnO NPs, the in vitro studies are certainly important to elucidate the mechanism of toxicity. This study examined the toxicity of ZnO NPs with the average size of 6 8 nm on the isolated mice bone marrow mesenchymal stem cells. The study focuses on the cytotoxicity and oxidative stress-mediated cellular responses upon exposure to ZnO NPs. The results indicated that the exposure to ZnO NPs significantly affects cellular viability in a dose-dependent manner. Formation of reactive oxygen species (ROS) was found to be the mechanism of cellular toxicity. The release of Zn(+) ions from the nanoparticles, due to the instability of ZnO NPs in the acidic compartment of lysosomes, also increases the ROS generation. In addition to increased ROS production, damage of lysosomal membrane and the activation of executioner caspase-3 and caspase-7 were observed, which eventually ends in apoptosis. PMID- 25138638 TI - Preparation of dibenzo[e,g]isoindol-1-ones via Scholl-type oxidative cyclization reactions. AB - A flexible synthesis of dibenzo[e,g]isoindol-1-ones has been developed. Dibenzo[e,g]isoindol-1-ones represent simplified benzenoid analogues of biological indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-ones (indolocarbazoles), compounds that have demonstrated a wide range of biological activity. The synthesis of the title compounds involved tetramic acid sulfonates. Different aryl groups were introduced at C4 of the heterocyclic ring via Suzuki-Miyaura cross-coupling reactions. Finally, mild Scholl-type oxidative cyclizations mediated by phenyliodine(III) bis(trifluoroacetate) (PIFA) converted some of the latter compounds into the corresponding dibenzo[e,g]isoindol-1-ones. A systematic study of the oxidative cyclization revealed the following reactivity trend: 3,4 dimethoxyphenyl ? 3-methoxyphenyl > 3,4,5-trimethoxyphenyl > 4-methoxyphenyl ~ phenyl. Overall, the oxidative cyclization required at least two methoxy groups distributed in the aromatic rings, at least one of which had to be located para to the site of the cyclization. PMID- 25138637 TI - G-protein-coupled receptor cell signaling pathways mediating embryonic chick retinal growth cone collapse induced by lysophosphatidic acid and sphingosine-1 phosphate. AB - In the development of the nervous system, one of the critical aspects is the proper navigation of axons to their targets, i.e. the problem of axonal guidance. We used the chick visual system as a model to investigate the role of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) as potential axon guidance cues. We showed that both LPA and S1P cause a specific, dose-dependent growth cone collapse of retinal neurons in vitro in the chick model system, with slight differences compared to the mouse but very similar to observations in Xenopus. Because LPA and S1P receptors are G-protein coupled receptors, we analyzed the intracellular signaling pathways using pharmacological inhibitors in chick retinal neurons. Blocking rho kinase (ROCK) prevented growth cone collapse by LPA and S1P, while blocking PLC or chelating calcium had no effect on growth cone collapse. Inhibition of Gi/o with pertussis toxin resulted in a partial reduction of growth cone collapse, both with LPA and with S1P. Inhibition of p38 blocked growth cone collapse mediated by LPA but not S1P. Thus, in addition to the involvement of the G12/13-ROCK pathway, LPA- and S1P-induced collapse of chick retinal growth cones has a partial requirement for Gi/o. PMID- 25138640 TI - Microorganism-induced suppression of allergic airway disease: novel therapies on the horizon? AB - Allergic airway disease is a major global health burden, and novel treatment options are urgently needed. Numerous epidemiological and experimental studies suggest that certain helminths and bacteria protect against respiratory allergies. These microorganisms are strong regulators of the immune system, and various potential regulatory mechanisms by which they protect against allergic airway inflammation have been proposed. Whereas early studies addressed the beneficial effect of natural infections, the focus now shifts toward identifying the dominant protective molecules and exploring their efficacy in models of allergic airway disease. In this article, we will review the evidence for microbe mediated protection from allergic airway disease, the potential modes of action involved and discuss advances as well as limitations in the translation of this knowledge into novel treatment strategies against allergic airway disease. PMID- 25138639 TI - The retrovirus/superantigen hypothesis of multiple sclerosis. AB - The pathogenesis of multiple sclerosis (MS) is as yet unknown. Commonly, MS is assumed to be due to an autoimmune inflammation of the central nervous system (CNS). Neurodegeneration is regarded to be a secondary reaction. This concept is increasingly being challenged. Human endogenous retroviruses (HERV) that could be locally activated in the CNS have been proposed as an alternative concept. HERV encoded envelope proteins (env) can act as strong immune stimulators (superantigens). Thus, slow disease progression following neurodegeneration might be induced by re-activation of HERV expression directly, while relapses in parallel to inflammation might be secondary to the expression of HERV-encoded superantigens. It has been shown previously that T-cell superantigens are capable to induce a cellular inflammatory reaction in the CNS of experimental animals similar to that in MS. Furthermore, B-cell superantigens have been shown to activate blood leucocytes in vitro to produce immunoglobulin in an oligoclonal manner. It remains to be established, whether the outlined hypothesis accords with all known features of MS. Furthermore, anti-HERV agents may be taken into consideration to enrich and improve MS therapy. PMID- 25138641 TI - A comparison of conventional methods for the quantification of bacterial cells after exposure to metal oxide nanoparticles. AB - BACKGROUND: Due to potential interference of nanoparticles on bacterial quantification, there is a challenge to develop a fast, accurate and reproducible method for bacterial quantification. Currently various bacterial quantification methods are used by researchers performing nanoparticles study, but there has been no efficacy evaluation of these methods. Here we study interference of nanoparticles on three most commonly used conventional bacterial quantification methods, including colony counting to determine the colony-forming units (CFU), spectrophotometer method of optical density (OD) measurement, and flow cytometry (FCM). RESULTS: Three oxide nanoparticles including ZnO, TiO2, and SiO2 and four bacterial species including Salmonella enterica serovar Newport, Staphylococcus epidermidis, Enterococcus faecalis, and Escherichia coli were included in the test. Results showed that there is no apparent interference of the oxide nanoparticles on quantifications of all four bacterial species by FCM measurement; CFU counting is time consuming, less accurate and not suitable for automation; and the spectrophotometer method using OD measurement was the most unreliable method to quantify and detect the bacteria in the presence of the nanoparticles. CONCLUSION: In summary, FCM measurement proved to be the best method, which is suitable for rapid, accurate and automatic detection of bacteria in the presence of the nanoparticles. PMID- 25138642 TI - Moderate alcohol exposure during early brain development increases stimulus response habits in adulthood. AB - Exposure to alcohol during early central nervous system development has been shown variously to affect aspects of physiological and behavioural development. In extreme cases, this can extend to craniofacial defects, severe developmental delay and mental retardation. At more moderate levels, subtle differences in brain morphology and behaviour have been observed. One clear effect of developmental alcohol exposure is an increase in the propensity to develop alcoholism and other addictions. The mechanisms by which this occurs, however, are not currently understood. In this study, we tested the hypothesis that adult zebrafish chronically exposed to moderate levels of ethanol during early brain ontogenesis would show an increase in conditioned place preference for alcohol and an increased propensity towards habit formation, a key component of drug addiction in humans. We found support for both of these hypotheses and found that the exposed fish had changes in mRNA expression patterns for dopamine receptor, nicotinic acetylcholine receptor and MU-opioid receptor encoding genes. Collectively, these data show an explicit link between the increased proclivity for addiction and addiction-related behaviour following exposure to ethanol during early brain development and alterations in the neural circuits underlying habit learning. PMID- 25138643 TI - Spatiotemporally consistent genomic signatures of reproductive isolation in a moving hybrid zone. AB - Studies of hybrid zone dynamics often investigate a single sampling period and draw conclusions from that temporal snapshot. Stochasticity can, however, result in loci with spurious outlier patterns, which is exacerbated by limited temporal or geographic sampling. Comparing admixed populations from different geographic regions is one way to detect repeatedly divergent genomic regions potentially involved in reproductive isolation. Temporal comparisons also allow us to control partially for the role of stochasticity, but the power of temporal sampling has not yet been adequately explored. In North America, black-capped (Poecile atricapillus) and Carolina (P. carolinensis) chickadees hybridize in a contact zone extending from New Jersey to Kansas. The hybrid zone is likely maintained by strong intrinsic selection against hybrids, and it is moving north. We used a reduced representation genomic approach and temporally spaced sampling-two samples of ~80 individuals separated by a decade-to determine the pattern and consistency of selection and genomic introgression in the chickadee hybrid zone. We report consistently low introgression for highly divergent loci between P. atricapillus and P. carolinensis in this moving hybrid zone. This is strong evidence that these loci may be linked to genomic regions involved in reproductive isolation between chickadees. PMID- 25138644 TI - SCAI expert consensus statement for renal artery stenting appropriate use. AB - The pathophysiology of atherosclerotic renal artery stenosis (RAS) includes activation of the renin-angiotensin-aldosterone axis with resultant renovascular hypertension. Renal artery stenting has emerged as the primary revascularization strategy in most patients with hemodynamically significant atherosclerotic RAS. Despite the frequency with which hemodynamically significant RAS is observed and high rates of technical success of renal artery stenting, there remains considerable debate among experts regarding the role of medical therapy versus revascularization for renovascular hypertension. Modern, prospective, multicenter registries continue to demonstrate improvement in systolic and diastolic blood pressure with excellent safety profiles in patients with RAS. Modern randomized, controlled clinical trials of optimal medical therapy versus renal stenting particularly designed to demonstrate preservation in renal function after renal artery stenting have demonstrated limited benefit. However, these trials frequently excluded patients that may benefit from renal artery stenting. This document was developed to guide physicians in the modern practical application of renal stenting, to highlight the current limitations in the peer-reviewed literature, to suggest best-practices in the performance of renal stenting and to identify opportunities to advance the field. PMID- 25138645 TI - Differences between motor point and innervation zone locations in the biceps brachii. An exploratory consideration for the treatment of spasticity with botulinum toxin. AB - BACKGROUND: Botulinum toxin (BTX) acts on the neuromuscular junction which can be located by the innervation zone (IZ). Clinically, the motor point (MP) is homologous to the IZ and it is used as the injection site of BTX. Differences in the effectiveness of the application of BTX between MP and IZ locations have been determined. OBJECTIVE: Compare the location of the MP obtained using electrical stimulation and the location of the IZ using a linear surface electrodes array on the biceps brachii muscle. METHODS: The biceps brachii muscle of twenty men was assessed. The MP was located using the torque measurement generated by electrical stimulation. The IZ was detected using a linear surface electrodes array. RESULTS: A difference between the MP and the IZ positions (75.8 vs. 86.5mm, delta 10.7 mm; p=0.003, post-hoc power 0.89) was observed. DISCUSSION: The magnitude of the difference between the MP and the IZ may be clinically relevant. The IZ location using surface electromyography as a guide to optimize BTX injection is proposed. PMID- 25138646 TI - Rigid and Elastic taping changes scapular kinematics and pain in subjects with shoulder impingement syndrome; an experimental study. AB - Rigid and Elastic scapular taping is used in physical rehabilitation of shoulder impingement syndrome (SIS). It is believed to reduce pain and normalise scapular movement patterns. However, there is insufficient evidence to support its use. The aim of the study was to investigate the effect of Rigid and Elastic taping techniques on the scapular kinematics and pain in patients with SIS. Eleven patients with SIS participated in the study. They performed elevation and lowering of the arm in the scapular and sagittal planes under three conditions: Baseline, Rigid taping and Elastic taping. The movements of the thorax, humerus and scapula were tracked. Scapular displacements and scapulothoracic joint rotations were calculated. Subjects used a visual analogue scale to rate the intensity of pain at rest and during movements in both planes. Both taping techniques externally rotated the scapula in sagittal plane movements (p<0.05) and resulted in reduced pain. In the scapular plane, Elastic taping increased the scapular retraction (p<0.05) and posterior displacement (p<0.01), but neither of the taping techniques had an effect on pain in this plane. In conclusion, both taping techniques had an effect on scapular kinematics and pain in movements occurring in the sagittal plane. Elastic taping also affected scapular kinematics in scapular plane movements, but without the concomitant decrease in pain. PMID- 25138648 TI - Factors Related to the Differential Preference for Cardiopulmonary Resuscitation Between Patients With Terminal Cancer and That of Their Respective Family Caregivers. AB - There is little information regarding concordance between preferences for end-of life care of terminally ill patients with cancer and those of their family caregivers. A cross-sectional exploration of cardiopulmonary resuscitation (CPR) preference in 361 dyads was conducted. Patients or family caregivers who were willing to approve CPR were compared with dyads who did not support CPR. The patient's quality of life was more associated with family caregiver's willingness than patient's willingness. A patient was more likely to prefer CPR than their caregiver in dyads of females and emotionally stable patients. A family caregiver showed stronger support for CPR if the patient had controlled pain or stable health and the family caregiver had not been counseled for CPR. Communications should be focused on these individuals to improve the planning of end-of-life care. PMID- 25138647 TI - Functional connectivity in frontal-striatal brain networks and cocaine self administration in female rhesus monkeys. AB - RATIONALE: Cocaine addiction is characterized by alternating cycles of abstinence and relapse and loss of control of drug use despite severe negative life consequences associated with its abuse. OBJECTIVE: The objective of the present study was to elucidate critical neural circuits involved in individual vulnerabilities to resumption of cocaine self-administration following prolonged abstinence. METHODS: The subjects were three female rhesus monkeys in prolonged abstinence following a long history of cocaine self-administration. Initial experiments examined the effects of acute cocaine administration (0.3 mg/kg, IV) on functional brain connectivity across the whole brain and in specific brain networks related to behavioral control using functional magnetic resonance imaging in fully conscious subjects. Subsequently, these subjects were allowed to resume cocaine self-administration to determine whether loss of basal connectivity within specific brain networks predicted the magnitude of resumption of cocaine intake following prolonged abstinence. RESULTS: Acute cocaine administration robustly decreased global functional connectivity and selectively impaired top-down prefrontal circuits that control behavior, while sparing connectivity of striatal areas within limbic circuits. Importantly, impaired connectivity between prefrontal and striatal areas during abstinence predicted cocaine intake when these subjects were provided renewed access to cocaine. CONCLUSIONS: Based on these findings, loss of prefrontal to striatal functional connectivity may be a critical mechanism underlying the negative downward spiral of cycles of abstinence and relapse that characterizes cocaine addiction. PMID- 25138649 TI - Knowledge About Hospice: Exploring Misconceptions, Attitudes, and Preferences for Care. AB - CONTEXT: Poor knowledge and misperceptions about hospice are believed to be common, but there is scant evidence about the public's understanding of hospice. OBJECTIVES: To examine hospice knowledge among geographically diverse adults; and describe linkages between knowledge, attitudes and beliefs about hospice care, and demographics. METHODS: A small cross-sectional telephone survey of adults living in the contiguous US was conducted using randomly selected numbers (cell phone and landline) and over-sampling of minorities. Measures assessed knowledge (23-item test), attitudes (8-item scale), experiences and preferences related to hospice. RESULTS: 123 participants completed surveys (response rate 46%). 106 (86%) had heard about hospice, 65 (54%) of whom had a personal experience with hospice. Participants had an average hospice knowledge test score of 18 (SD = 3.4) indicating moderate knowledge of hospice. A majority of respondents (62%) did not know that hospice cannot provide concurrent cure-oriented care. Misperceptions about eligibility, coverage of hospice, the provision of hospice in nursing homes or to persons who live alone were not uncommon (missed by >20%). Greater knowledge of hospice was associated with more favorable attitudes about the hospice philosophy of care (r = .22, p = .023) and a greater preference for hospice (p = .049). Respondents who were more educated, worked in the medical field, were non-Hispanic White, and had direct experience with hospice were also more likely to be more knowledgeable about hospice. CONCLUSION: Despite relatively high hospice awareness and favorability, myths and misperceptions about hospice still abound--and may drive ethnic disparities in end-of-life care. Educational interventions and future study are needed. PMID- 25138651 TI - Effect of diet- and lifestyle-based metabolic risk-modifying interventions on preeclampsia: a meta-analysis. AB - OBJECTIVE: To evaluate the effect of dietary and lifestyle interventions with the potential to modify metabolic risk factors on the risk of preeclampsia. DATA SOURCES: We searched MEDLINE, EMBASE and Cochrane from inception until February 2013. Randomized trials in pregnant women evaluating the effect of dietary and lifestyle interventions with the potential to modify metabolic risks such as obesity, hyperlipidemia, hyperglycemia and hypertension on the risk of preeclampsia were included. STUDY SELECTION: Two independent reviewers selected studies, extracted data and assessed quality. Results were summarized as pooled relative risks (RR) for dichotomous data. RESULTS: Eighteen studies (8712 women) met our search criteria for inclusion. Six studies evaluated diet (2695 women), six studied mixed interventions with diet, physical activity and lifestyle (1438 women) and six assessed essential fatty acid supplementation (4579 women). The interventions overall reduced the risk of preeclampsia (RR 0.81, 95% CI 0.69 0.94; p = 0.006 I(2) = 0%) compared with the control group. Dietary interventions reduced the risk of preeclampsia by 33% (RR 0.67, 95% CI 0.53-0.85; p = 0.001; I(2) = 0%). There was no reduction in the risk of preeclampsia with mixed interventions (RR 0.93, 95% CI 0.66-1.32, p = 0.68, I(2) = 0%) or fatty acid supplementation (RR 0.92, 95% CI 0.71-1.18; p = 0.49, I(2) = 15%). Meta regression showed a borderline impact of gestational diabetes status (p = 0.05) on the observed effect. CONCLUSION: Dietary and lifestyle interventions have the potential to reduce the risk of preeclampsia. The effect of additional therapeutic interventions in women with gestational diabetes mellitus on preeclampsia is not known. PMID- 25138650 TI - Circadian variation of mineral and bone parameters in end-stage renal disease. AB - BACKGROUND: Mineral and bone parameters are actively managed in end-stage renal disease (ESRD). However, whether these undergo circadian variation is not known. We investigated the circadian variation of mineral and bone parameters in patients on long-term hemodialysis. METHODS: Seventeen ESRD patients on long-term hemodialysis and eight volunteers without kidney disease were enrolled. Subjects had all medications that affect calcium-phosphate-parathyroid hormone balance (phosphate binders, vitamin D analogues, and calcimimetics) discontinued. Thereafter, for a period of 5 days, subjects consumed a diet controlled in calcium (1,200 mg per day) and phosphorus (1,000 mg per day) content. On the sixth day (a non-dialysis day for the ESRD patients), enrollees underwent twelve 2-h blood draws for phosphate, ionized calcium, parathyroid hormone (PTH), total 25-hydroxy vitamin D (25OHD), and fibroblast growth factor-23 (FGF-23). RESULTS: In the ESRD patients plasma phosphate demonstrated significant circadian variation (P < 0.00001). The peak occurred around 3:30 am and nadir occurred around 11:00 am. Ionized calcium (P = 0.0036), PTH (P = 0.0004) and 25OHD (P = 0.009) also varied significantly during the circadian period; for ionized calcium peak and nadir occurred around 12:15 pm and 8:00 pm, parathyroid hormone 5:45 pm and 10:15 am, and 25OHD 9:45 am and 4:00 pm respectively. FGF-23 did not show a significant circadian variation. Only phosphate (P < 0.0001) and PTH (P = 0.00008) demonstrated circadian variation in the control group. CONCLUSIONS: Blood concentrations of phosphate, calcium, PTH and 25-hydroxy vitamin D, exhibit a circadian variation in patients with ESRD. Knowledge of these phenomena is pertinent for the interpretation of clinical testing. PMID- 25138652 TI - CoroEval: a multi-platform, multi-modality tool for the evaluation of 3D coronary vessel reconstructions. AB - We present a software, called CoroEval, for the evaluation of 3D coronary vessel reconstructions from clinical data. It runs on multiple operating systems and is designed to be independent of the imaging modality used. At this point, its purpose is the comparison of reconstruction algorithms or acquisition protocols, not the clinical diagnosis. Implemented metrics are vessel sharpness and diameter. All measurements are taken from the raw intensity data to be independent of display windowing functions. The user can either import a vessel centreline segmentation from other software, or perform a manual segmentation in CoroEval. An automated segmentation correction algorithm is provided to improve non-perfect centrelines. With default settings, measurements are taken at 1 mm intervals along the vessel centreline and from 10 different angles at each measurement point. This allows for outlier detection and noise-robust measurements without the burden and subjectivity a manual measurement process would incur. Graphical measurement results can be directly exported to vector or bitmap graphics for integration into scientific publications. Centreline and lumen segmentations can be exported as point clouds and in various mesh formats. We evaluated the diameter measurement process using three phantom datasets. An average deviation of 0.03 +/- 0.03 mm was found. The software is available in binary and source code form at http://www5.cs.fau.de/CoroEval/. PMID- 25138653 TI - Time to gain trust and change--experiences of attachment and mindfulness-based cognitive therapy among patients with chronic pain and psychiatric co-morbidity. AB - The treatment of patients with chronic pain disorders is complex. In the rehabilitation of these patients, coping with chronic pain is seen as important. The aim of this study was to explore the meaning of attachment and mindfulness based cognitive therapy (CT) among patients with chronic pain and psychiatric co morbidity. A phenomenological approach within a lifeworld perspective was used. In total, 10 patients were interviewed after completion of 7- to 13-month therapy. The findings reveal that the therapy and the process of interaction with the therapist were meaningful for the patients' well-being and for a better management of pain. During the therapy, the patients were able to initiate a movement of change. Thus, CT with focus on attachment and mindfulness seems to be of value for these patients. The therapy used in this study was adjusted to the patients' special needs, and a trained psychotherapist with a special knowledge of patients with chronic pain might be required. PMID- 25138654 TI - Stiff muscle fibers in calf muscles of patients with cerebral palsy lead to high passive muscle stiffness. AB - Cerebral palsy (CP), caused by an injury to the developing brain, can lead to alterations in muscle function. Subsequently, increased muscle stiffness and decreased joint range of motion are often seen in patients with CP. We examined mechanical and biochemical properties of the gastrocnemius and soleus muscles, which are involved in equinus muscle contracture. Passive mechanical testing of single muscle fibers from gastrocnemius and soleus muscle of patients with CP undergoing surgery for equinus deformity showed a significant increase in fiber stiffness (p<0.01). Bundles of fibers that included their surrounding connective tissues showed no stiffness difference (p=0.28).). When in vivo sarcomere lengths were measured and fiber and bundle stiffness compared at these lengths, both fibers and bundles of patients with CP were predicted to be much stiffer in vivo compared to typically developing (TD) individuals. Interestingly, differences in fiber and bundle stiffness were not explained by typical biochemical measures such as titin molecular weight (a giant protein thought to impact fiber stiffness) or collagen content (a proxy for extracellular matrix amount). We suggest that the passive mechanical properties of fibers and bundles are thus poorly understood. PMID- 25138655 TI - Controls on foliar nutrient and aluminium concentrations in a tropical tree flora: phylogeny, soil chemistry and interactions among elements. AB - Foliar elemental concentrations are predictors of life-history variation and contribute to spatial patterns in biogeochemical cycling. We examined the contributions of habitat association, local soil environment, and elemental interactions to variation in foliar elemental concentrations in tropical trees using methods that account for phylogeny. We sampled top-soils and leaves of 58 tropical trees in heath forest (HF) on nutrient-poor sand and mixed dipterocarp forest (MDF) on nutrient-rich clay soils. A phylogenetic generalized least squares method was used to determine how foliar nutrient and aluminium (Al) concentrations varied in response to habitat distribution, soil chemistry and other elemental concentrations. Foliar nitrogen (N) and Al concentrations were greater for specialists of MDF than for specialists of HF, while foliar calcium (Ca) concentrations showed the opposite trend. Foliar magnesium (Mg) concentrations were lower for generalists than for MDF specialists. Foliar element concentrations were correlated with fine-scale variation in soil chemistry in phylogenetically controlled analyses across species, but there was limited within-species plasticity in foliar elemental concentrations. Among Al accumulators, foliar Al concentration was positively associated with foliar Ca and Mg concentrations, and negatively associated with foliar phosphorus (P) concentrations. The Al-accumulation trait and relationships between foliar elemental and Al concentrations may contribute to species habitat partitioning and ecosystem-level differences in biogeochemical cycles. PMID- 25138657 TI - Stoichiometrically controlled revocable self-assembled "spiro" versus quadruple stranded "double-decker" type coordination cages. AB - The simple combination of Pd(II) with the tris-monodentate ligand bis(pyridin-3 ylmethyl) pyridine-3,5-dicarboxylate, L, at ratios of 1:2 and 3:4 demonstrated the stoichiometrically controlled exclusive formation of the "spiro-type" Pd1L2 macrocycle, 1, and the quadruple-stranded Pd3L4 cage, 2, respectively. The architecture of 2 is elaborated with two compartments that can accommodate two units of fluoride, chloride, or bromide ions, one in each of the enclosures. However, the entry of iodide is altogether restricted. Complexes 1 and 2 are interconvertible under suitable conditions. PMID- 25138656 TI - Iron oxide encapsulated by ruthenium hydroxyapatite as heterogeneous catalyst for the synthesis of 2,5-diformylfuran. AB - Magnetic gamma-Fe2 O3 nanocrystallites encapsulated by hydroxyapatite (HAP), HAP@gamma-Fe2 O3 , were prepared followed by cation exchange of Ca(2+) on the external HAP surface with Ru(3+) to give the gamma-Fe2 O3 @HAP-Ru catalyst. The structure of the as-prepared catalyst was characterized, and its catalytic activity was studied in the aerobic oxidation of 5-hydroxymethylfurfural (HMF). gamma-Fe2 O3 @HAP-Ru showed a high catalytic activity for the aerobic oxidation of HMF into 2,5-diformylfuran (DFF). A high DFF yield of 89.1 % with an HMF conversion of 100% was obtained after 4 h at 90 degrees C. Importantly, the synthesis of DFF from fructose was realized by two consecutive steps. The dehydration of fructose in the presence of a magnetic acid catalyst (Fe3 O4 @SiO2 SO3 H) produced HMF in a yield of 90.1%. Then the Fe3 O4 @SiO2 ?SO3 H catalyst was removed from the reaction solution with a permanent magnet, and HMF in the resulting solution was further oxidized to DFF with a yield of 79.1% based on fructose. The synthesis of DFF from fructose by two steps avoids the tedious separation of the intermediate HMF, which saves time and energy. PMID- 25138658 TI - [Visual experiences during cataract surgery under topical anesthesia]. AB - BACKGROUND: Cataract patients observe structures, colors and movements during surgery. Is there any pattern to their visual experiences? METHODS: From 2005 to 2011 a total of 20,000 phacoemulsification procedures were performed using topical anesthesia. From these patients we received 45 pictures which had been painted to reflect intraoperative their visual impressions so that approximately 1 out of 500 of the patients painted a picture. A further 98 patients were questioned postoperatively about their intraoperative visual impressions and were shown the 45 pictures. They described their own visual experiences and any similarities with the 45 pictures were documented. RESULTS: All patients were awake and cooperative during surgery. Afterwards they described their visual experiences whereby 36 patients saw mainly blue, 32 red/pink and 27 saw yellow colors. Out of the 45 pictures 30 (67%) were identified as being similar to their own visual images and 10 patients could not describe any postoperative visual phenomena. CONCLUSION: Patients notice optical phenomena during cataract surgery under topical anesthesia with eye drops. Visual images are often similar among patients. The surgeon can use this knowledge to explain these experiences while talking to the patient intraoperatively. This may reassure patients during surgery. PMID- 25138659 TI - Resource utilization pattern and cost of tuberculosis treatment from the provider and patient perspectives in the state of Penang, Malaysia. AB - BACKGROUND: Studies from both developed and developing countries have demonstrated a considerable fluctuation in the average cost of TB treatment. The objective of this study was to analyze the medical resource utilization among new smear positive pulmonary tuberculosis patients. We also estimated the cost of tuberculosis treatment from the provider and patient perspectives, and identified the significant cost driving factors. METHODS: All new smear positive pulmonary tuberculosis patients who were registered at the chest clinic of the Penang General Hospital, between March 2010 and February 2011, were invited to participate in the study. Provider sector costs were estimated using bottom-up, micro-costing technique. For the calculation of costs from the patients' perspective, all eligible patients who agreed to participate in the study were interviewed after the intensive phase and subsequently at the end of the treatment by a trained nurse. PASW was used to analyze the data (Predictive Analysis SoftWare, version 19.0, Armonk, NY: IBM Corp.). RESULTS: During the study period, 226 patients completed the treatment. However, complete costing data were available for 212 patients. The most highly utilized resources were chest X-ray followed by sputum smear examination. Only a smaller proportion of the patients were hospitalized. The average provider sector cost was MYR 992.34 (i.e., USD 325.35 per patient) whereby the average patient sector cost was MYR 1225.80 (i.e., USD 401.90 per patient). The average patient sector cost of our study population accounted for 5.7% of their annual family income. In multiple linear regression analysis, prolonged treatment duration (i.e., > 6 months) was the only predictor of higher provider sector costs whereby higher patient sector costs were determined by greater household income and persistent cough at the end of the intensive phase of the treatment. CONCLUSION: In relation to average provider sector cost, our estimates are substantially higher than the budget allocated by the Ministry of Health for the treatment of a tuberculosis case in Malaysia. The expenses borne by the patients and their families on the treatment of the current episode of tuberculosis were not catastrophic for them. PMID- 25138660 TI - Association of congenital left renal vein anomalies and unexplained hematuria: multidetector computed tomography findings. AB - OBJECTIVES: To investigate whether congenital renal vein anomalies are involved in the etiology of hematuria by analyzing abdominal multidetector computed tomography (MDCT) results. METHODS: Six hundred and eighty patients undergoing MDCT for various abdominal pathologies in whom possible causes of hematuria were excluded were retrospectively assessed in terms of left renal vein anomalies, such as circumaortic left renal vein (CLRV), retroaortic left renal vein (RLRV) and multiple renal vein (MRV). Patients with CLRV, RLRV or MRV and patients with normal left renal veins were compared in terms of the presence of hematuria. RESULTS: Left renal vein anomalies were detected in 100 patients (14.7%). RLRV, CLRV and MRV were identified in 5.4, 2.5 and 6.8% of patients, respectively. Hematuria was determined in 8.1% of patients with an RLRV anomaly and in 10.5% of patients with no RLRV anomaly (p=0.633). Hematuria was detected in 23.5% of patients with a CLRV anomaly and 10.1% of those without (p=0.074), and in 21.7% of patients with an MRV anomaly and 9.6% of those without (p=0.009). CONCLUSIONS: In addition to increasing risk of complication during retroperitoneal surgery, numeric congenital renal vein anomalies are also significant in terms of leading to clinical symptoms such as hematuria. PMID- 25138661 TI - Satiety effects of a whole-grain fibre composite ingredient: reduced food intake and appetite ratings. AB - The current study assesses the impact on appetite and food intake of a novel co processed ingredient containing a viscous fibre and whole-grain high-amylose corn flour, a source of type 1 and type 2 resistant starch (HAM-RS). Ninety adults completed a crossover, placebo-controlled study comparing two doses of the ingredient (20 and 30 g) to a maltodextrin control in a fruit-based smoothie served with breakfast. Ad libitum food intake was measured over the day and visual analogue scales were used to assess subjective appetite sensations. Subjects consumed 7% less energy intake at dinner following the 30 g dose (p = 0.02) compared to control. In addition, a trend for lower lunch intake (5% less weight of food) was observed for the 20 g dose (p = 0.10). Reductions were also observed for the two meals combined, with 3% lower energy intake for the 20 g dose (p = 0.04) and 5% less weight of food consumed for the 30 g dose (p = 0.04). Lower ratings of hunger were reported at 3 h after breakfast for both doses and also at 2 and 3 h after lunch for the 30 g dose. With ratings combined to compute an overall appetite score, a trend for lower appetite scores at 3 h after breakfast was found for both doses. Consistent with this, significant reductions in AUC hunger and prospective consumption were identified in the 30 g condition. A similar pattern of results was observed for fullness and desire to eat. The results of this study show that a new composite satiety ingredient comprised of a viscous fibre and whole-grain corn flour can affect acute satiety responses in men and women. PMID- 25138663 TI - DNA replication timing: Coordinating genome stability with genome regulation on the X chromosome and beyond. AB - Recent studies based on next-generation DNA sequencing have revealed that the female inactive X chromosome is replicated in a rapid, unorganized manner, and undergoes increased rates of mutation. These observations link the organization of DNA replication timing to gene regulation on one hand, and to the generation of mutations on the other hand. More generally, the exceptional biology of the inactive X chromosome highlights general principles of genome replication. Cells may control replication timing by a combination of intrinsic replication origin properties, local chromatin states and global levels of replication factors, leading to a functional separation between the activity of genes and their mutation. PMID- 25138664 TI - The role of jet eccentricity in generating disproportionately elevated transaortic pressure gradients in patients with aortic stenosis. AB - In patients with aortic stenosis (AS) and eccentric transaortic flow, greater pressure loss occurs as the jet collides with the aortic wall together with delayed and diminished pressure recovery. This leads to the elevated transaortic valve pressure gradients noted on both Doppler and cardiac catheterization. Such situations may present a diagnostic dilemma where traditional measures of stenosis severity indicate severe AS, while imaging modalities of the aortic valve geometric aortic valve area (GOA) suggest less than severe stenosis. In this study, we present a series of cases exemplifying this clinical dilemma and demonstrate how color M-mode, 2D and 3D transthoracic (TTE) and transesophageal (TEE) echocardiography, cardiac computed tomography angiography (CTA), and magnetic resonance imaging (MRI), may be used to resolve such discrepancies. PMID- 25138662 TI - The evolution of mitochondrial genomes in modern frogs (Neobatrachia): nonadaptive evolution of mitochondrial genome reorganization. AB - BACKGROUND: Although mitochondrial (mt) gene order is highly conserved among vertebrates, widespread gene rearrangements occur in anurans, especially in neobatrachians. Protein coding genes in the mitogenome experience adaptive or purifying selection, yet the role that selection plays on genomic reorganization remains unclear. We sequence the mitogenomes of three species of Glandirana and hot spots of gene rearrangements of 20 frog species to investigate the diversity of mitogenomic reorganization in the Neobatrachia. By combing these data with other mitogenomes in GenBank, we evaluate if selective pressures or functional constraints act on mitogenomic reorganization in the Neobatrachia. We also look for correlations between tRNA positions and codon usage. RESULTS: Gene organization in Glandirana was typical of neobatrachian mitogenomes except for the presence of pseudogene trnS (AGY). Surveyed ranids largely exhibited gene arrangements typical of neobatrachian mtDNA although some gene rearrangements occurred. The correlation between codon usage and tRNA positions in neobatrachians was weak, and did not increase after identifying recurrent rearrangements as revealed by basal neobatrachians. Codon usage and tRNA positions were not significantly correlated when considering tRNA gene duplications or losses. Change in number of tRNA gene copies, which was driven by genomic reorganization, did not influence codon usage bias. Nucleotide substitution rates and dN/dS ratios were higher in neobatrachian mitogenomes than in archaeobatrachians, but the rates of mitogenomic reorganization and mt nucleotide diversity were not significantly correlated. CONCLUSIONS: No evidence suggests that adaptive selection drove the reorganization of neobatrachian mitogenomes. In contrast, protein-coding genes that function in metabolism showed evidence for purifying selection, and some functional constraints appear to act on the organization of rRNA and tRNA genes. As important nonadaptive forces, genetic drift and mutation pressure may drive the fixation and evolution of mitogenomic reorganizations. PMID- 25138673 TI - Identification of synergistic Cu/V redox pair in VCu:AlPO-5; a comparison with VCu:ZSM-5. AB - Vanadium(V) and copper(II) were co-deposited into AlPO-5 and H-ZSM-5 three dimensional microporous carriers to yield VCu:AlPO-5 and VCu:ZSM-5. The materials, along with copper analogues were tested for the selective oxidation of propene, and the catalysts perform in the following order: VCu:AlPO-5 > Cu:AlPO-5 > VCu:ZSM-5 > Cu:ZSM-5. Acrolein was selectively formed over VCu:AlPO-5 and Cu:AlPO-5 over a very wide range from 300 to 450 degrees C, whereas VCu:ZSM-5 displays a limited temperature window for acrolein formation (300-350 degrees C). Hence, the choice of carrier and presence of vanadium as a co-cation greatly affects the acrolein selectivity and activity window. The vanadium and copper reduction events were monitored by in situ X-ray Absorption Spectroscopy (XAS) during C3H6-TPR (1.11%) to 450 degrees C. The Cu(II)/(I) redox pair initiates reduction of V(V) -> V(IV) in VCu:AlPO-5 and VCu:ZSM-5 at 375 degrees C. Metallic copper is the major valence fraction above 400 degrees C in both samples while vanadium is present as V(IV)/V(III) species. In the monometallic copper analogues Cu(I) is the major valence fraction above 350 degrees C, hence synergistic effects between the Cu/V pair causes hyper-reduction of copper. EXAFS shows that copper and vanadium are in close proximity in VCu:AlPO-5 only, being linked by bridging oxygens (Cu-O-V) believed to interact with propene. By contrast, propene adsorbs on Bronsted sites in VCu:ZSM-5 inhibiting acrolein formation at elevated temperatures, as confirmed by DRIFTS. We believe the reactive Cu/V pair in neutral AlPO-5 generates extralattice oxygens favouring acrolein formation over a wide temperature range. PMID- 25138665 TI - An in vitro model of innate lymphoid cell function and differentiation. AB - Innate lymphoid cells (ILC) are RAG-independent lymphocytes with important roles in innate immunity, and include group-1 (natural killer (NK) cell, ILC1), group-2 (ILC2), and group-3 (lymphoid tissue inducer (LTi), NCR(+) ILC3) subsets. Group-3 ILC express Rorgammat, produce interleukin (IL)-22, and are critically important in the normal function of mucosal tissues. Here, we describe a novel model cell line for the study of ILC function and differentiation. The parental MNK cell line, derived from NKR-P1B(+) fetal thymocytes, shows a capacity to differentiate in gammac cytokines. One IL-7-responsive subline, designated MNK-3, expresses Rorgammat and produces high levels of IL-22 in response to IL-23 and IL-1beta stimulation. MNK-3 cells display surface markers and transcript expression characteristic of group-3 ILC, including IL-7Ralpha (CD127), c-kit (CD117), CCR6, Thy1 (CD90), RANK, RANKL, and lymphotoxin (LTalpha1beta2). Using an in vitro assay of LTi cell activity, MNK-3 cells induce ICAM-1 and VCAM-1 expression on stromal cells in a manner dependent upon LTalpha1beta2 expression. A second IL-2 responsive subline, MNK-1, expresses several NK cell receptors, perforin and granzymes, and shows some cytotoxic activity. Thus, MNK-1 cells serve as a model of ILC1/NK development and differentiation, whereas MNK-3 cells provide an attractive in vitro system to study the function of ILC3/LTi cells. PMID- 25138672 TI - Acupuncture increases the diameter and reorganisation of collagen fibrils during rat tendon healing. AB - BACKGROUND: Our previous study showed that electroacupuncture (EA) increases the concentration and reorganisation of collagen in a rat model of tendon healing. However, the ultrastructure of collagen fibrils after acupuncture is unknown. OBJECTIVES: To assess the effect of acupuncture protocols on the ultrastructure of collagen fibrils during tendon healing. METHODS: Sixty-four rats were divided into the following groups: non-tenotomised (normal group), tenotomised (teno group), tenotomised and subjected to manual acupuncture at ST36 (ST36 group), BL57 (BL57 group) and ST36+BL57 (SB group) and EA at ST36+BL57 (EA group). The mass-average diameter (MAD) and the reorganisation of collagen fibril diameters were determined during the three phases of tendon healing (at 7, 14 and 21 days). RESULTS: The MAD increased during the three phases of healing in the SB group. In the EA group, MAD increased initially but was reduced at day 21. The reorganisation of collagen fibrils was improved in the EA and SB groups at days 14 and 21, respectively. EA at day 21 appeared to reduce the reorganisation. CONCLUSIONS: These results indicate that the use of EA up to day 14 and manual acupuncture at ST36+BL57 up to day 21 improve the ultrastructure of collagen fibrils, indicating strengthening of the tendon structure. These data suggest a potential role for acupuncture in rehabilitation protocols. PMID- 25138666 TI - CCR2(+)CD103(-) intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells. AB - The identification of intestinal macrophages (mphis) and dendritic cells (DCs) is a matter of intense debate. Although CD103(+) mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103(-) MPs remain controversial. We show here that intestinal CD103(-)CD11b(+) MPs can be separated clearly into DCs and mphis based on phenotype, gene profile, and kinetics. CD64(-)CD103( )CD11b(+) MPs are classical DCs, being derived from Flt3 ligand-dependent, DC committed precursors, not Ly6C(hi) monocytes. Surprisingly, a significant proportion of these CD103(-)CD11b(+) DCs express CCR2 and there is a selective decrease in CD103(-)CD11b(+) DCs in mice lacking this chemokine receptor. CCR2(+)CD103(-) DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2(+) DCs that is involved in priming mucosal T helper type 17 (Th17) responses. PMID- 25138674 TI - Photobleaching reveals heterogeneous stoichiometry for equinatoxin II oligomers. AB - Equinatoxin II (EqtII), a sea anemone cytolysin, is known to oligomerize to form pores that spontaneously insert into membranes. Crystallographic and cryo-EM studies of structurally similar cytolysins offer contradictory evidence for pore stoichiometry. Here we used single-molecule photobleaching of fluorescently labeled EqtII to determine the stoichiometry of EqtII oligomers in supported lipid bilayers. A frequency analysis of photobleaching steps revealed a log normal distribution of stoichiometries with a mean of 3.4+/-2.3 standard deviations. Comparison of our experimental data with simulations of fixed stoichiometries supports our observation of a heterogeneous distribution of EqtII oligomerization. These data are consistent with a model of EqtII stoichiometry where pores are on average tetrameric, but with large variation in the number of subunits in individual pores. PMID- 25138675 TI - Characterization of an organic solvent-tolerant thermostable glucoamylase from a halophilic isolate, Halolactibacillus sp. SK71 and its application in raw starch hydrolysis for bioethanol production. AB - A halophilic bacterium Halolactibacillus sp. SK71 producing extracellular glucoamylase was isolated from saline soil of Yuncheng Salt Lake, China. Enzyme production was strongly influenced by the salinity of growth medium with maximum in the presence of 5% NaCl. The glucoamylase was purified to homogeneity with a molecular mass of 78.5 kDa. It showed broad substrate specificity and raw starch hydrolyzing activity. Analysis of hydrolysis products from soluble starch by thin layer chromatography revealed that glucose was the sole end-product, indicating the enzyme was a true glucoamylase. Optimal enzyme activity was found to be at 70 degrees C, pH 8.0, and 7.5% NaCl. In addition, it was highly active and stable over broad ranges of temperature (0-100 degrees C), pH (7.0-12.0), and NaCl concentration (0-20%), showing excellent thermostable, alkali stable, and halotolerant properties. Furthermore, it displayed high stability in the presence of hydrophobic organic solvents. The purified glucoamylase was applied for raw corn starch hydrolysis and subsequent bioethanol production using Saccharomyces cerevisiae. The yield in terms of grams of ethanol produced per gram of sugar consumed was 0.365 g/g, with 71.6% of theoretical yield from raw corn starch. This study demonstrated the feasibility of using enzymes from halophiles for further application in bioenergy production. PMID- 25138676 TI - Synthesis of composites SBA-15 mesoporous particles carrying oxytocin and evaluation of their properties, functions, and in vitro biological activities. AB - Using the organic template method, we have synthesized mesoporous SBA-15 particles and characterized them by scanning electron microscopy and transmission electron microscopy. The bone metabolism regulating hormone oxytocin (OT) was selected as a model for preparation of drug/SBA-15 complexes. The process of drug loading was studied using X-ray diffraction and nitrogen absorption methods. Optimal drug loading parameters were experimentally investigated. The kinetics of drug release from the carrier was evaluated. Finally, the extractions of SBA-15 particles were tested for cytotoxicity, in vitro hemolysis, and the direct attachment toxicity. Our findings suggest that SBA-15 materials have good biocompatibility. Moreover, we demonstrated that OT/SBA-15 complex can stimulate alkaline phosphatase activity in osteoblast cells. The study provides fundamental information for further in vivo drug-carrier testing. PMID- 25138678 TI - Immunoglobulin G4-related paratesticular fibrous pseudotumor and retroperitoneal fibrosis: a case report. AB - A 46-year-old man with a past history of retroperitoneal fibrosis was admitted with an enlarged, hard right testis. The paratesticular lesion showed heterogeneous hypoechogenicity on ultrasonography, low signal intensity on T1- and T2-weighted magnetic resonance imaging (MRI), and lack of diffusion restriction on diffusion-weighted MRI. Following steroid treatment, the paratesticular mass was decreased in size on follow-up computed tomography. The radiologic and clinical features are recognized as a manifestation of immunoglobulin G4-related sclerosing disease involving the paratesticular region and retroperitoneum. PMID- 25138679 TI - Ursodeoxycholic acid, an inhibitor of hepatocyte nuclear factor 1alpha, did not increase the systemic exposure of pitavastatin. AB - OBJECTIVE: Pitavastatin, a highly potent inhibitor of 3-hydroxy methylglutarylcoenzyme A reductase, is a known substrate of OATP1B1. Ursodeoxycholic acid (UDCA) inhibits OATP1B1 expression by repressing hepatocyte nuclear factor 1alpha (HNF1alpha). Thus, the effects of UDCA on the pharmacokinetics of pitavastatin were investigated in healthy subjects. METHODS: An open-label, 2-phase, parallel study was conducted with 13 healthy volunteers. In the control phase, after an overnight fast, each subject received a single dose of 2 mg pitavastatin. After a 1-week washout period, in the UDCA phase, subjects received a daily oral dose of 600 mg of UDCA (300 mg b.i.d.) for 14 days. On day 15, 2 mg of pitavastatin was administered as described previously for the control phase. RESULTS: In the UDCA phase, the maximum plasma concentration (C(max)) of pitavastatin was slightly higher than in the control phase (48.6 +/- 22.9 ng/mL vs. 42.4 +/- 16.1 ng/mL). However, the overall pharmacokinetic parameters of pitavastatin and pitavastatin lactone during the two study phases were not significantly different. CONCLUSIONS: UDCA had no significant effect on the pharmacokinetics of pitavastatin. These results do not support the notion that UDCA increases the systemic exposure of OATP1B1 substrate by inhibiting HNF1alpha and decreasing OATP1B1 transporter expression. PMID- 25138677 TI - Characterization of dsRed2-positive cells in the doublecortin-dsRed2 transgenic adult rat retina. AB - Doublecortin (DCX) is predominantly expressed in neuronal precursor cells and young immature neurons of the developing and adult brain, where it is involved in neuronal differentiation, migration and plasticity. Moreover, its expression pattern reflects neurogenesis, and transgenic DCX promoter-driven reporter models have been previously used to investigate adult neurogenesis. In this study, we characterize dsRed2 reporter protein-expressing cells in the adult retina of the transgenic DCX promoter-dsRed2 rat model, with the aim to identify cells with putative neurogenic activity. Additionally, we confirmed the expression of the dsRed2 protein in DCX-expressing cells in the adult hippocampal dentate gyrus. Adult DCX-dsRed2 rat retinas were analyzed by immunohistochemistry for expression of DCX, NF200, Brn3a, Sox2, NeuN, calbindin, calretinin, PKC-a, Otx2, ChAT, PSA NCAM and the glial markers GFAP and CRALBP, followed by confocal laser-scanning microscopy. In addition, brain sections of transgenic rats were analyzed for dsRed2 expression and co-localization with DCX, NeuN, GFAP and Sox2 in the cortex and dentate gyrus. Endogenous DCX expression in the adult retina was confined to horizontal cells, and these cells co-expressed the DCX promoter-driven dsRed2 reporter protein. In addition, we encountered dsRed2 expression in various other cell types in the retina: retinal ganglion cells (RGCs), a subpopulation of amacrine cells, a minority of bipolar cells and in perivascular cells. Since also RGCs expressed dsRed2, the DCX-dsRed2 rat model might offer a useful tool to study RGCs in vivo under various conditions. Muller glial cells, which have previously been identified as cells with stem cell features and with neurogenic potential, did express neither endogenous DCX nor the dsRed2 reporter. However, and surprisingly, we identified a perivascular glial cell type expressing the dsRed2 reporter, enmeshed with the glia/stem cell marker GFAP and colocalizing with the neural stem cell marker Sox2. These findings suggest the so far undiscovered existence of perivascular associated cell with neural stem cell-like properties in the adult retina. PMID- 25138680 TI - Open-label, 2-period sequential drug interaction study to evaluate the effect of a 100-mg dose of desvenlafaxine on the pharmacokinetics of tamoxifen when coadministered in healthy postmenopausal female subjects. AB - BACKGROUND: Potential drugdrug interactions are a concern for patients taking tamoxifen. OBJECTIVE: This study was designed to determine the effect of coadministering desvenlafaxine on tamoxifen pharmacokinetics. MATERIALS AND METHODS: This open-label, 2-period inpatient and outpatient study enrolled healthy, postmenopausal women. Period 1, day 1, subjects were administered tamoxifen 40 mg followed by 23 days of blood sampling for pharmacokinetic analyses. During period 2, subjects received desvenlafaxine 100 mg/d for 28 days; a single dose of tamoxifen 40 mg was administered with desvenlafaxine 100 mg on day 7, followed by 23 days of blood sampling. Pharmacokinetics of tamoxifen and its metabolites (AUC over infinite time (AUC(inf)), AUC to the last measurable concentration (AUC(last)), peak plasma concentration (C(max)) were compared for monotherapy vs. combination therapy using the ratio of adjusted mean differences. A superposition method was used in the statistical analysis of N-desmethyl tamoxifen and endoxifen to address the carry-over observed for those metabolites. The test for interaction was considered negative if the 90% confidence intervals (CIs) for the ratios were within 80 - 125%. RESULTS: Coadministration of tamoxifen with steady-state desvenlafaxine did not alter tamoxifen AUC(inf), AUC(last), and C(max), as reflected by the ratio of adjusted geometric means (90% CIs) of 100.7% (96.7%, 104.9%), 103.5% (100.2%, 106.9%), and 99.4% (94.0%, 105.2%), respectively. Similarly, coadministration did not alter 4-hydroxy- tamoxifen and N-desmethyl-amoxifen pharmacokinetics. The 11.8% (88.2% (82.6%, 94.2%)) and 8.0% (92.0% (84.7%, 100.0%)) decreases in endoxifen AUC(last) and C(max), respectively, were not significant (90% CIs fell wholly within the prespecified acceptance range). CONCLUSIONS: Steady-state desvenlafaxine 100 mg did not affect tamoxifen pharmacokinetics. For women treated with tamoxifen, desvenlafaxine may represent a safe and effective treatment unlikely to alter tamoxifen efficacy. PMID- 25138681 TI - Implications of different application sites on the bioavailability of a transdermal contraceptive patch containing ethinyl estradiol and gestodene: an open-label, randomized, crossover study. AB - OBJECTIVES: A novel once-a-week contraceptive patch delivers the same systemic exposure seen with a combined oral contraceptive pill containing 0.02 mg ethinyl estradiol (EE) and 0.06 mg gestodene (GSD). This study evaluated the relative bioavailability of EE and GSD after application of this patch to three different sites. METHODS: In this phase I, open-label, randomized, intra-individual comparison, crossover study, 43 women (aged 18 - 45 years) were randomized to one of six treatment sequences. Patches were applied to two test sites (buttocks and outer, upper arm) and one comparator site (lower abdomen). In each treatment period, four patches were worn for 7 days each, followed by a 7-day, patch-free interval. The primary objective was to investigate the relative bioavailability of transdermally administered EE and GSD between test and comparator sites using the primary variable area under the concentration- time curve (AUC(0-168)) during week 4 of each period. RESULTS: Of the 43 women who were randomized, 43 were included in the set for safety evaluation and 40 were included in the set for pharmacokinetic (PK) analysis. Three subjects were excluded from the PK analysis as they failed to complete the study. AUC(0-168) for EE and GSD were equal when the patch was applied to buttocks or abdomen (AUC(0-168) ratios: EE, 1.07 (94% confidence interval, CI: 0.994 - 1.16); GSD, 1.02 (94% CI: 0.946 - 1.10)). Relative bioavailabilities for EE and GSD were 31% and 24% higher, respectively, for arm vs. abdomen. AUC(0-168) 94% CI for the arm/abdomen ratio exceeded the pre defined bioequivalence range of 80 - 125% (EE: 1.21 - 1.42; GSD: 1.15 - 1.34). Other PK parameters were correspondingly higher for arm vs. buttocks or abdomen. Patch adhesion and tolerability were good, with no relevant differences between sites. CONCLUSION: Differences in systemic EE/GSD exposure following patch application to the outer, upper arm vs. lower abdomen and buttocks are unlikely to be clinically relevant, and there were no relevant safety concerns. PMID- 25138682 TI - Pharmacokinetics of vorapaxar and its metabolite following oral administration in healthy Chinese and American subjects. AB - AIM: Vorapaxar is a proteaseactivated receptor (PAR)-1 antagonist being developed for the prevention and treatment of thrombotic vascular events. To evaluate race/ethnic differences between Caucasians and Chinese in the pharmacokinetics of vorapaxar and its active metabolite SCH 2046273 (M20) or in the metabolite/parent ratio, we conducted a cross-study comparison on pharmacokinetic data of vorapaxar and M20 obtained from two similarly designed studies: one in healthy Chinese subjects and the other in a healthy Western (United States, [U.S.]) population. METHODS: The pharmacokinetic profiles of vorapaxar and M20 were characterized using open label, two treatment parallel group designs in men and women aged 18 - 45 years. Vorapaxar was administered orally as a single dose of 40 mg in Chinese subjects (n = 14) or 120 mg in U.S. subjects (n = 14), or 2.5 mg QD for 6 weeks in both studies (Chinese, n = 14; U.S., n = 23). RESULTS: Vorapaxar was rapidly absorbed in both Chinese and U.S. subjects. Vorapaxar and M20 had similar elimination half-lives. The range of metabolite/parent ratios after single dose or daily administration was largely overlapped in Chinese and U.S. subjects. Steady state was attained by day 21 for vorapaxar and M20 in both race/ethnic groups. The accumulation ratios for vorapaxar and M20 during daily administration were similar in Chinese and U.S. subjects. Vorapaxar was well-tolerated in Chinese and U.S. subjects. CONCLUSION: The pharmacokinetic profiles of vorapaxar and M20 and the metabolite/parent ratios in healthy Chinese were generally comparable to those in a healthy Western population. PMID- 25138683 TI - Ultrafast photoswitching in a copper-nitroxide-based molecular magnet. AB - Molecular compounds with photoswitchable magnetic properties have been intensively investigated over the last decades due to their prospective applications in nanoelectronics, sensing and magnetic data storage. The family of copper-nitroxide-based molecular magnets represents a new promising type of photoswitchable compounds. We report the first study of these appealing systems using femtosecond optical spectroscopy. We unveil the mechanism of ultrafast (<50 fs) spin state photoswitching and establish its principal differences compared to other photoswitchable magnets. On this basis, we propose potential advantages of copper-nitroxide-based molecular magnets for the future design of ultrafast magnetic materials. PMID- 25138684 TI - Development of necrotising fasciitis in a patient treated for rheumatoid arthritis with tocilizumab. PMID- 25138685 TI - Reliability and validity of the pain on movement questionnaire (POM) in chronic neck pain. AB - OBJECTIVE: This analysis aimed to determine reliability, validity, and responsiveness of the pain on movement (POM) questionnaire, an instrument developed to determine pain intensity induced by head movement. DESIGN: Data from nine randomized controlled trials for the treatment of chronic nonspecific neck pain were reanalyzed to determine reliability and validity of the POM questionnaire. METHODS: POM was assessed as ratings of pain intensity induced by head movement in six different directions. The instrument's structure was assessed using a factor analysis. Reliability (internal consistency) was determined using Cronbach's alpha, and validity (convergent validity) was determined by correlating the POM with pain at rest on a visual analog scale (VAS), the neck disability index (NDI), quality of life (short-form 36 health survey questionnaire [SF-36]) and range of motion. Responsiveness was indicated by sensitivity to changes over time in a subsample of 49 patients. RESULTS: Overall, 482 patients (mean age 50.3 +/- 12.4 years, 72.3% female) were included in the analysis, and 458 of them provided complete data set for the POM. Average POM was 43.9 +/- 20.8 mm on the VAS. The POM showed very good reliability as indicated by high internal consistency and moderate validity as indicated by significant correlations with the pain at rest, the NDI, and the SF-36. No correlations were found for POM with range of motion. The POM further proved to be responsive as it was sensitive to changes over time, and those changes were correlated to changes in pain intensity and NDI. CONCLUSIONS: The POM seems to be a reliable and valid instrument to assess POM in patients with chronic nonspecific neck pain. PMID- 25138686 TI - PML nuclear bodies: regulation, function and therapeutic perspectives. AB - PML nuclear bodies (NBs) were first described by electron microscopy and rediscovered through their treatment-reversible disruption in a rare leukaemia. They recruit multiple partner proteins and now emerge as interferon- and oxidative stress-responsive sumoylation factories. NBs mediate interferon-induced viral restriction, enhance proteolysis, finely tune metabolism and enforce stress induced senescence. Apart from being markers of cellular stress, PML NBs could be harnessed pharmacologically in a number of conditions, including cancer, viral infection or neurodegenerative diseases. PMID- 25138687 TI - Another casualty of sibling fixed-effects analysis of education and health: an informative null, or null information? PMID- 25138688 TI - From policy to practice: implementing frontline community health services for substance dependence--study protocol. AB - BACKGROUND: Substance abuse is a worldwide public health concern. Extensive scientific research has shown that screening and brief interventions for substance use disorders administered in primary care provide substantial benefit at relatively low cost. Frontline health clinicians are well placed to detect and treat patients with substance use disorders. Despite effectiveness shown in research, there are many factors that impact the implementation of these practices in real-world clinical practice. Recently, the Ministry of Health and Social Services in Quebec, Canada, issued two policy documents aimed at introducing screening and early intervention for substance abuse into frontline healthcare clinics in Quebec. The current research protocol was developed in order to study the process of implementation of evidence-based addiction treatment practices at three primary care clinics in Montreal (Phase 1). In addition, the research protocol was designed to examine the efficacy of overall policy implementation, including barriers and facilitators to addictions program development throughout Quebec (Phase 2). METHODS/DESIGN: Phase 1 will provide an in-depth case study of knowledge translation and implementation. The study protocol will utilize an integrated knowledge translation strategy to build collaborative mechanisms for knowledge exchange between researchers, addiction specialists, and frontline practitioners (guided by the principles of participatory-action research), and directly examine the process of knowledge uptake and barriers to transfer using both qualitative and quantitative methodologies. Evaluation will involve multiple measures, time points and domains; program uptake and effectiveness will be determined by changes in healthcare service delivery, sustainability and outcomes. In Phase 2, qualitative methods will be utilized to examine the contextual facilitators and barriers that frontline organizations face in implementing services for substance dependence. Phase 2 will provide the first study exploring the wide-scale implementation of frontline services for substance dependence in the province of Quebec and yield needed information about how to effectively implement mandated policies into clinical practice and impact public health. DISCUSSION: Findings from this research program will contribute to the understanding of factors associated with implementation of frontline services for substance dependence and help to inform future policy and organizational support for the implementation of evidence-based practices. PMID- 25138689 TI - Mean platelet volume is a prognostic factor in patients with acute kidney injury requiring continuous renal replacement therapy. AB - PURPOSE: Platelet size has been demonstrated to reflect platelet activity and to predict poor clinical outcomes in patients with cardiovascular disease. However, the prognostic value of platelet size for mortality has not been studied in patients with acute kidney injury (AKI). MATERIALS AND METHODS: A total of 349 patients who received continuous renal replacement therapy (CRRT) for AKI between August 2009 and October 2011 were divided into 2 groups based on the median mean platelet volume (MPV) at the time of CRRT initiation. Twenty-eight-day mortality rate was determined using Kaplan-Meier plots and time-dependent receiver operating characteristic curves were constructed. In addition, multivariate Cox analysis for mortality was used to evaluate the independent prognostic value of MPV. RESULTS: The mean age was 61.3 years, and 218 patients (62.5%) were male. At the initiation of CRRT, MPV level was inversely correlated with platelet count, whereas it was positively associated with Acute Physiology and Chronic Health Evaluation II scores. During the study period, 231 deaths (66.2%) occurred. Kaplan-Meier curve showed that 28-day all-cause mortality was significantly higher in patients with MPV>=10.2 fL compared with those with MPV<10.2 fL (P<.001). Moreover, Cox regression analysis revealed that MPV was an independent predictor for 28-day all-cause mortality after adjustment of age, age-adjusted Charlson Comorbidity Index, cause of AKI, platelet count, Acute Physiology and Chronic Health Evaluation II score, presence of malignancy, albumin, and C reactive protein (hazard ratio, 1.080; 95% confidence interval, 1.010-1.155; P=.023). CONCLUSION: Mean platelet volume at the time of CRRT initiation may be an inexpensive and useful predictor for 28-day all-cause mortality in patients with AKI requiring CRRT. PMID- 25138690 TI - Association between transient acute kidney injury and morbidity and mortality after lung transplantation: a retrospective cohort study. AB - PURPOSE: Acute kidney injury (AKI) is a common occurrence after lung transplantation (LTx). Whether transient AKI or early recovery is associated with improved outcome is uncertain. Our aim was to describe the incidence, factors, and outcomes associated with transient AKI after LTx. MATERIALS AND METHODS: We performed a retrospective cohort study of all adult recipients of LTx at the University of Alberta between 1990 and 2011. Our primary outcome transient AKI was defined as return of serum creatinine below Kidney Disease-Improving Global Outcome AKI stage I within 7days after LTx. Secondary outcomes included occurrence of postoperative complications, mortality, and long-term kidney function. RESULTS: Of 445 LTx patients enrolled, AKI occurred in 306 (68.8%) within the first week after LTx. Of these, transient AKI (or early recovery) occurred in 157 (51.3%). Transient AKI was associated with fewer complications including tracheostomy (17.2% vs 38.3%; P<.001), reintubation (16.4% vs 41.9%; P<.001), decreased duration of mechanical ventilation (median [interquartile range], 69 [41-142] vs 189 [63-403] hours; P<.001), and lower rates of chronic kidney disease at 3 months (28.5% vs 51.1%, P<.001) and 1 year (49.6% vs 66.7%, P=.01) compared with persistent AKI. Factors independently associated with persistent AKI were higher body mass index (per unit; odds ratio [OR], 0.91; 95% confidence interval, 0.85-0.98; P=.01), cyclosporine use (OR, 0.29; 0.12-0.67; P=.01), longer duration of mechanical ventilation (per hour [log transformed]; OR, 0.42; 0.21-0.81; P=.01), and AKI stages II to III (OR, 0.16; 0.08-0.29; P<.001). Persistent AKI was associated with higher adjusted hazard of death (hazard ratio, 1.77 [1.08-2.93]; P=.02) when compared with transient AKI (1.44 [0.93-2.19], P=.09) and no AKI (reference category), respectively. CONCLUSIONS: Transient AKI after LTx is associated with fewer complications and improved survival. Among survivors, persistent AKI portends an increased risk for long term chronic kidney disease. PMID- 25138693 TI - Cytoarchitecture of the telencephalon in the coral reef multiband Butterflyfish ( Chaetodon multicinctus : Perciformes). AB - Detailed neuroanatomical studies of model species are necessary to facilitate comparative experiments which test hypotheses relevant to brain evolution and function. Butterflyfishes (Chaetodontidae) boast numerous sympatric species that differ in social behavior, aggression and feeding ecology. However, the ability to test hypotheses relevant to brain function in this family is hindered by the lack of detailed neural descriptions. The cytoarchitecture of the telencephalon in the monogamous and territorial multiband butterflyfish, Chaetodon multicinctus, was determined with Nissl-stained serial sections and an immunohistochemical analysis of arginine vasotocin (AVT), serotonin, substance P and tyrosine hydroxylase. The ventral telencephalon was similar to that of other perciform fishes studied, with one major difference. A previously undescribed postcommissural region, the cuneate nucleus, was identified and putatively assigned to the ventral telencephalon. While the function of this nucleus is unknown, preliminary studies indicate that it may be part of a behaviorally relevant subpallial neural circuit that is modulated by AVT. The dorsal telencephalon consisted of 15 subdivisions among central, medial, lateral, dorsal and posterior zones. Several regions of the dorsal telencephalon of C. multicinctus differed from many other perciform fishes examined thus far. The nucleus taenia was in a more caudal position, and the central and lateral zones were enlarged. Within the lateral zone, an unusual third, ventral subdivision and a large-celled division were present. One hypothesis is that the enlarged ventral subdivision of the lateral zone (potential hippocampus homolog) relates to an enhancement of spatial learning or olfactory memory, which are important for this coral reef fish. This study provides the neuroanatomical basis for future comparative and evolutionary studies of brain organization and neuropeptide distributions, physiological studies of neural processing and insight into the complex social behavior of butterflyfishes. PMID- 25138692 TI - Effect of enamel protective agents on shear bond strength of orthodontic brackets. AB - BACKGROUND: This paper aimed to study the effect of two enamel protective agents on the shear bond strength (SBS) of orthodontic brackets bonded with conventional and self-etching primer (SEP) adhesive systems. METHODS: The two protective agents used were resin infiltrate (ICON) and Clinpro; the two adhesive systems used were self-etching primer system (Transbond Plus Self Etching Primer + Transbond XT adhesive) and a conventional adhesive system (37% phosphoric acid etch + Transbond XT primer + Transbond XT adhesive ). Sixty premolars divided into three major groups and six subgroups were included. The shear bond strength was tested 72 h after bracket bonding. Adhesive remnant index scores (ARI) were assessed. Statistical analysis consisted of a one-way ANOVA for the SBS and Kruskal-Wallis test followed by Mann-Whitney test for the ARI scores. RESULTS: In the control group, the mean SBS when using the conventional adhesive was 21.1 +/- 7.5 MPa while when using SEP was 20.2 +/- 4.0 MPa. When ICON was used with the conventional adhesive system, the SBS was 20.2 +/- 5.6 MPa while with SEP was 17.6 +/- 4.1 MPa. When Clinpro was used with the conventional adhesive system, the SBS was 24.3 +/- 7.6 MPa while with SEP was 11.2 +/- 3.5 MPa. Significant differences in the shear bond strength of the different groups (P = .000) was found as well as in the ARI scores distribution (P = .000). CONCLUSION: The type of the adhesive system used to bond the orthodontic brackets, either conventional or self-etching primer, influenced the SBS, while the enamel protective material influenced the adhesive remnant on the enamel surface after debonding. PMID- 25138694 TI - How does obesity affect fertility in men - and what are the treatment options? AB - Adiposity is associated with reduced fertility in men. The aetiology is multifactorial, with obese men at greater risk of suffering from impaired spermatogenesis, reduced circulating testosterone levels, erectile dysfunction and poor libido. The diagnosis and treatment of reduced fertility observed in obese men therefore requires insight into the underlying pathology, which has hormonal, mechanical and psychosocial aspects. This article summarises the current epidemiological, experimental and clinical trial evidence from the perspective of a practicing clinician. The following conclusions and recommendations can be drawn: Obesity is associated with low serum testosterone concentrations, but treatment with exogenous testosterone is likely to adversely impact on fertility. It is important to discuss this with men prior to initiation of testosterone therapy. Obesity adversely affects sperm concentration and may affect sperm quality. However, whether or not weight loss will correct these factors remain to be established. Oestrogen receptor modulators (and aromatase inhibitors) are unlicensed in the treatment for male hypogonadism and/or infertility. These treatments should hence be considered experimental approach until ongoing clinical trials report their outcomes. PMID- 25138695 TI - Coacervate delivery systems for proteins and small molecule drugs. AB - Coacervates represent an exciting new class of drug delivery vehicles, developed in the past decade as carriers of small molecule drugs and proteins. This review summarizes several well-described coacervate systems, including: i) elastin-like peptides for delivery of anticancer therapeutics; ii) heparin-based coacervates with synthetic polycations for controlled growth factor delivery; iii) carboxymethyl chitosan aggregates for oral drug delivery; iv) Mussel adhesive protein and hyaluronic acid coacervates. Coacervates present advantages in their simple assembly and easy incorporation into tissue engineering scaffolds or as adjuncts to cell therapies. They are also amenable to functionalization such as for targeting or for enhancing the bioactivity of their cargo. These new drug carriers are anticipated to have broad applications and noteworthy impact in the near future. PMID- 25138696 TI - Effects of ventral pallidal D1 dopamine receptor activation on memory consolidation in morris water maze test. AB - In the present experiments, in adult male Wistar rats, the effect of microinjection of the D1 dopamine receptor agonist SKF38393 into the ventral pallidum on memory consolidation, as well as on resistance of the resulting memory trace against extinction were investigated in Morris water maze test. SKF38393 was applied in three doses (0.1, 1.0 or 5.0MUg in 0.4MUl physiological saline, respectively). To clarify whether the effect of the agonist was specific, in a separate group of animals, the D1 dopamine receptor antagonist SCH23390 (5.0MUg in 0.4MUl physiological saline) was administered 15min prior to 1.0MUg agonist treatment. In another group of animals, the same dose of antagonist was applied by itself. The two lower doses (0.1 and 1.0MUg) of the agonist accelerated memory consolidation relative to controls and increased the stability of the consolidated memory trace against extinction. Antagonist pretreatment eliminated the effects of the agonist, thus confirming that the effect was selectively specific to D1 dopamine receptors. Our findings indicate that the ventral pallidal D1 dopamine receptors are intimately involved in the control of the consolidation processes of spatial memory. PMID- 25138697 TI - Frequency-dependent changes in the amplitude of low-frequency fluctuations in subcortical ischemic vascular disease (SIVD): a resting-state fMRI study. AB - Resting-state functional magnetic resonance imaging (RS-fMRI) allowed researchers to detect intrinsic brain activity during rest and has been considered an analytical tool for evaluation of dementia. Previously, subcortical ischemic vascular disease (SIVD) has been found decreased amplitude low-frequency fluctuations (ALFF) in a widely frequency range (0.01-0.08Hz) in the bilateral precuneus and increased ALFF values in the bilateral anterior cingulate cortex (ACC), left insula and hippocampus, which showed significant correlations with the cognitive performance. In this study we analyzed the ALFF of 30 patients with SIVD in two different frequency bands (slow-5: 0.01-0.027Hz; slow-4: 0.027 0.073Hz). In the slow-5 band, SIVD patients compared with controls exhibited significant higher ALFF in the bilateral anterior cingulate cortex, right putamen and right supplementary motor area, while lower ALFF in the right precuneus and right angular gyrus. A close correlation was found between the ALFF value of the right angular gyrus and ADL scores. In the slow-4 band, SIVD patients only exhibited increased ALFF in the bilateral anterior cingulate cortex, right putamen, left fusiform gyrus, and no correlation with cognitive scores was found. Our data demonstrate that SIVD patients have widespread abnormal intrinsic neural oscillations, which are dependent on specific frequency bands. ALFF of right angular gyrus at slow-5 band is more specific for SIVD and may be a useful tool to help SIVD diagnosis. PMID- 25138698 TI - King-Devick test normative reference values for professional male ice hockey players. AB - The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye movements, has shown promise as a supplemental screening test following concussion. However, limited normative data for this test have been published.The K-D test was administered to 185 professional ice hockey players as a preseason baseline test in seasons 2012-2013 and 2013-2014. Their average age was 23.8 years (median = 22.0 years, range = 16-40 years). The average K-D score was 40.0 s (SD = 6.1 s, range = 24.0-65.7 s). K-D test performance showed no association with age, education, or the number of self-reported previous concussions in this sample. The association between trials 1 and 2 of the K-D test was good (ICC = 0.92, Pearson = 0.93). Normative values of the K-D test for professional male ice hockey players are reported. K-D test performance did not vary by age, education, or concussion history in this study. PMID- 25138699 TI - Dietary LC-PUFA in iron-deficient anaemic pregnant and lactating guinea pigs induce minor defects in the offsprings' auditory brainstem responses. AB - OBJECTIVES: We previously demonstrated that a mild pre-natal/early post-natal iron-deficient anaemic (IDA) diet devoid of long-chain polyunsaturated fatty acids (LC-PUFA) affected development, neurophysiology, and cerebral lipid biochemistry of the guinea pigs' progeny. Impacts of dietary LC-PUFA on altered cerebral development resulting from pre-natal IDA are unknown. To address this health issue, impacts of mild gestational IDA in the presence of dietary LC-PUFA on the offsprings' neural maturation were studied in guinea pigs using auditory brainstem responses (ABRs) and assessments of brain fatty acids (FAs). METHODS: Female guinea pigs (n = 10/group) were fed an iron sufficient (IS) or IDA diet (146 and 12.7 mg iron/kg, respectively) with physiological amounts of LC-PUFA, during the gestation and lactation periods. From post-natal day (PNd) 9 onwards, the IS + PUFA diet was given to both groups of weaned offspring. Cerebral tissue and offsprings' ABR were collected on PNd24. RESULTS: There was no difference in peripheral and brainstem transmission times (BTTs) between IS + PUFA and IDA + PUFA siblings (n = 10/group); the neural synchrony was also similar in both groups. Despite the absence of differences in auditory thresholds, IDA + PUFA siblings demonstrated a sensorineural hearing loss in the extreme range of frequencies (32, 4, and 2 kHz), as well as modified brain FA profiles compared to the IS + PUFA siblings. DISCUSSION: The present study reveals that siblings born from dams exposed to a moderate IDA diet including balanced physiological LC-PUFA levels during pregnancy and lactation demonstrate minor impairments of ABR compared to the control siblings, particularly on the auditory acuity, but not on neural synchrony, auditory nerve velocity and BTT. PMID- 25138700 TI - Decreased BMP2 signal in GIT1 knockout mice slows bone healing. AB - Endochondral ossification, an important stage of fracture healing, is regulated by a variety of signaling pathways. Transforming growth factor beta (TGFbeta) superfamily plays important roles and comprises TGFbetas, bone morphogenetic proteins (BMPs), and growth differentiation factors. TGFbetas primarily regulate cartilage formation and endochondral ossification. BMP2 shows diverse efficacy, from the formation of skeleton and extraskeletal organs to the osteogenesis and remodeling of bone. G-protein-coupled receptor kinase 2-interacting protein-1 (GIT1), a shuttle protein in osteoblasts, facilitates fracture healing by promoting bone formation and increasing the secretion of vascular endothelial growth factor. Our study examined whether GIT1 regulates fracture healing through the BMP2 signaling pathway and/or through the TGFbeta signaling pathway. GIT1 knockout (KO) mice exhibited delayed fracture healing, chondrocyte accumulation in the fracture area, and reduced staining intensity of phosphorylated Smad1/5/8 (pSmad1/5/8) and Runx2. Endochondral mineralization diminished while the staining intensity of phosphorylated Smad2/3 (pSmad2/3) showed no significant change. Bone marrow mesenchymal stem cells extracted from GIT1 KO mice showed a decline of pSmad1/5/8 levels and of pSmad1/5/8 translocated into the cell nucleus after BMP2 stimulus. We detected no significant change in the pSmad2/3 level after TGFbeta1 stimulus. Data obtained from reporter gene analysis of C3H10T1/2 cells cultured in vitro confirmed these findings. GIT1-siRNA inhibited transcription in the cell nucleus via pSmad1/5/8 after BMP2 stimulus but had no significant effect on transcription via pSmad2/3 after TGFbeta1 stimulus. Our results indicate that GIT1 regulates Smad1/5/8 phosphorylation and mediates BMP2 regulation of Runx2 expression, thus affecting endochondral ossification at the fracture site. PMID- 25138701 TI - TGF-beta1 enhances SDF-1-induced migration and tube formation of choroid-retinal endothelial cells by up-regulating CXCR4 and CXCR7 expression. AB - Stromal derived factor (SDF)-1 has been confirmed to regulate angiogenesis in choroidal neovascularization formation via its two receptors, CXC chemokine receptors 4 (CXCR4) and 7 (CXCR7). Previous studies found that there is cross talk between the transforming growth factor beta (TGF-beta) and SDF-1 pathways in some types of immune or tumor cells, but much less is known about this interaction in endothelial cells. This study investigated the effects of TGF beta1 on CXCR4 and CXCR7 expression as well as SDF-1-induced migration and tube formation in choroid-retinal endothelial (RF/6A) cells. RF/6A cells were treated with recombinant TGF-beta1 at various concentrations and time points. Real-time PCR and Western blotting were used to examine the mRNA and protein levels of CXCR4 and CXCR7. In addition, transwell migration and Matrigel tube formation analyses were performed to investigate the role of TGF-beta1 pretreatment in SDF 1-induced RF/6A cell migration and tube formation. Our results showed that treatment with recombinant human TGF-beta1 enhanced the CXCR4 and CXCR7 levels in time- and dose-dependent manners. The increased CXCR4 and CXCR7 expression resulted in increased SDF-1-induced RF/6A cell migration and tube formation. In addition, the transcriptional regulation of CXCR4 and CXCR7 by TGF-beta1 was found to be mediated by phosphorylation of the extracellular signal-related kinase1/2 pathway. Altogether, these results demonstrate that a cross-talk exists between the TGF-beta1 and SDF-1 pathways in choroid-retinal endothelial cells, reflecting a novel molecular mechanism that explains the pro-angiogenic effects of TGF-beta1 and possibly provides new perspectives for the treatment of CNV associated diseases. PMID- 25138702 TI - Apollon/Bruce is upregulated by Humanin. AB - Humanin, a short bioactive peptide, inhibits a variety of cell deaths. Humanin mediated inhibition of neuronal cell death, caused by an Alzheimer's disease (AD) linked mutant gene occurs via binding of Humanin to its heterotrimeric Humanin receptor (htHNR), which results in the activation of the Janus-associated kinases (JAKs) and signal transducer and activator and transcription 3 (STAT3) signaling pathway. A previous study demonstrated that the Humanin-induced activation of the htHNR/JAK2/STAT3 signaling pathway leads to increased expression of SH3 domain binding protein 5 (SH3BP5), which is an essential effector of Humanin's anti-cell death activity in some cultured neuronal cells. However, it remains unknown whether SH3BP5 is the sole effector of the Humanin signaling pathway via htHNR/JAKs/STAT3. Here we show that the Humanin signaling pathway via htHNR/JAKs/STAT3 increased the expression levels of mRNA and protein of Apollon/Bruce, an unusual member of the inhibitors of apoptosis proteins, and that overexpression of Apollon/Bruce inhibits neuronal death, caused by a London type familial AD-linked mutant (V642I) of amyloid beta precursor protein. Overall, the results indicate that expression of Apollon/Bruce is upregulated by Humanin, and Apollon/Bruce could be an effector of Humanin in a context-dependent manner. PMID- 25138703 TI - Coordinated regulation of autophagy and apoptosis determines endothelial cell fate during Dengue virus type 2 infection. AB - Dengue is the most prevalent mosquito-borne viral disease in tropical regions. Severe cases may progress to Dengue hemorrhagic fever, suggesting vascular endothelial dysfunction in disease pathogenesis. In our previous study, we found that Dengue virus type 2 (DENV2) induced apoptosis of vascular endothelial cells via FasL/Fas- and XIAP-associated factor 1 (XAF1)-dependent pathways. In this paper, we demonstrate that DENV2 can induce autophagy in primary human umbilical vein endothelial cells (HUVECs) and the human umbilical vein endothelial cell line EA.hy926. Inhibition of autophagy with 3-methyl adenine promoted apoptosis, while inhibition of apoptosis with Z-VAD-FMK facilitated autophagy in DENV2 infected HUVECs and EA.hy926 cells. Interferon-alpha-inducible protein 6 (IFI6), a putative apoptosis regulator, inhibited DENV2-induced autophagy in EA.hy926 cells, while XAF1, an inhibitor of anti-apoptotic XIAP, facilitated autophagy. Molecular regulators of apoptosis and autophagy interact at multiple levels to determine cell fate. Our data suggest that XAF1 and IFI6 are involved in regulating the balance between autophagy and apoptosis in DENV2-infected endothelial cells. PMID- 25138706 TI - Comparative evaluation of seven different sample treatment approaches for large scale multiclass sport drug testing in urine by liquid chromatography-mass spectrometry. AB - Sample preparation is a critical step in large-scale multiclass analysis such as sport drug testing. Due to the wide heterogeneity of the analytes and the complexity of the matrix, the selection of a correct sample preparation method is essential, looking for a compromise between good recoveries for most of the analytes and cleanliness of the extract. In the present work, seven sample preparation procedures based on solid-phase extraction (SPE) (with 5 different cartridges), liquid-liquid extraction (LLE) and sorbent-supported liquid extraction (SLE) were evaluated for multiclass sport drug testing in urine. The selected SPE sorbents were polymeric cartridges Agilent PLEXATM and Oasis HLBTM, mixed mode cation and anion exchange cartridges Oasis MAXTM and MCXTM, and C18 cartridges. LLE was performed using tert-butyl methyl ether and SLE was carried out using Agilent Chem ElutTM cartridges. To evaluate the proposed extraction procedures, a list of 189 compounds were selected as representative from different groups of doping agents, including 34 steroids, 14 glucocorticosteroids, 24 diuretics and masking agents, 11 stimulants, 9 beta agonist, 16 beta-blockers, 6 Selective Estrogen Receptors Modulators (SERMs), 24 narcotics and 22 other drugs of abuse/sport drugs. Blank urine samples were spiked at two levels of concentration, 2.5 and 25MUgL(-1) and extracted with the different extraction protocols (n=6). The analysis of the extracts was carried out by liquid chromatography electrospray time-of-flight mass spectrometry. The use of solid-phase extraction with polymer cartridges provided high recoveries for most of the analytes tested and was found the more suitable method for this type of application given the additional advantages such as low sample and solvent consumption along with increased automation and throughput. PMID- 25138704 TI - Epigenetic modifications and NF-kappaB pathway activity in Cu,Zn-SOD-deficient mice. AB - The aim of this study was to examine the possible impact of Cu,Zn-SOD deficiency on the level of epigenetic modifications in different mouse tissues, and the relationship between these modifications and the NF-kappaB transcription factor activity. Cu,Zn-SOD deficiency did not influence the level of 5mdC or 5hmdC in the analyzed tissues. Statistically significant organ-/tissue-specific differences between the levels of 5mdC and 5hmdC were demonstrated within each genotype. Also correlations between analyzed parameters pointed to wide tissue/genotype variety; we observed a positive correlation between 5mdC and NF kB proteins, p50 and RelA, in the liver of wild mice, as well as an inverse correlation between 5mdC and p65 in the brain of Cu,Zn-SOD-deficient animals. Moreover, a positive correlation was revealed between 5mdC and 5hmdC in the liver and brain of knockout mice. As the highest levels of both 5mdC and 5hmdC were observed in the brains of analyzed animals regardless of their genotype, and lower, comparable to each other, levels of these modifications were shown in the kidney and liver, active demethylation process seems to be tissue-/organ-specific and does not necessarily rely solely on the redox/oxidation state of cells. According to the most likely scenario, various tissues may differ in terms of their metabolic rates, which has potential influence on cofactors, and consequently on the activity of TET enzymes or activation of TET-independent mechanisms. PMID- 25138707 TI - Dynamic high performance liquid chromatography on chiral stationary phases. Low temperature separation of the interconverting enantiomers of diazepam, flunitrazepam, prazepam and tetrazepam. AB - Diazepam and the structurally related 1,4-benzodiazepin-2-ones tetrazepam, prazepam and flunitrazepam are chiral molecules because they adopt a ground state conformation featuring a non-planar seven membered ring devoid of any reflection symmetry element. The two conformational enantiomers of this class of benzodiazepines interconvert rapidly at room temperature by a simple ring flipping process. Low temperature HPLC on the Whelk-O1 chiral stationary phase allowed us to separate the conformational enantiomers of diazepam and of the related 1,4-benzodiazepin-2-ones, under conditions where the interconversion rate is sufficiently low, compared to the chromatographic separation rate. Diazepam, tetrazepam and prazepam showed temperature dependent dynamic HPLC profiles with interconversion plateaus indicative of on-column enantiomer interconversion (enantiomerization) in the temperature range between -10 degrees C and -35 degrees C, whereas for flunitrazepam on-column interconversion was observed at temperatures between -40 degrees C and -66 degrees C. Simulation of exchange deformed HPLC profiles using a computer program based on the stochastic model yielded the apparent rate constants for the on-column enantiomerization and the corresponding free energy activation barriers. At -20 degrees C the enantiomerization barriers, DeltaG(?), for diazepam, prazepam and tetrazepam were determined to be in the range 17.6-18.7 kcal/mol. At -55 degrees C DeltaG(?) for flunitrazepam was determined to be in the 15.6-15.7 kcal/mol range. The experimental dynamic chromatograms and the corresponding interconversion barriers reported in this paper call for a reinterpretation of previously published results on the HPLC behavior of diazepam on chiral stationary phases. PMID- 25138705 TI - Hormonal regulation of the cytokine microenvironment in the mammary gland. AB - The mammary gland is a unique organ that undergoes hormone-driven developmental changes over the course of the ovarian cycle during adult life. Macrophages play a role in regulating cellular turnover in the mammary gland and may affect cancer susceptibility. However, the immune microenvironment that regulates macrophage function has not been described. Hormonal regulation of the cytokine microenvironment across the ovarian cycle was explored using microbead multiplex assay for 15 cytokines in mammary glands from C57Bl/6 mice at different stages of the oestrous cycle, and in ovariectomised mice administered oestradiol and progesterone. The cytokines that were found to fluctuate over the course of the oestrous cycle were colony-stimulating factor (CSF)1, CSF2, interferon gamma (IFNG) and tumour necrosis factor alpha (TNFA), all of which were significantly elevated at oestrus compared with other phases. The concentration of serum progesterone during the oestrus phase negatively correlated with the abundance of cytokines CSF3, IL12p40, IFNG and leukaemia inhibitory factor (LIF). In ovariectomised mice, exogenous oestradiol administration increased mammary gland CSF1, CSF2, IFNG and LIF, compared with ovariectomised control mice. Progesterone administration together with oestradiol resulted in reduced CSF1, CSF3 and IFNG compared with oestradiol administration alone. This study suggests that the cytokine microenvironment in the mammary gland at the oestrus phase of the ovarian cycle is relatively pro-inflammatory compared with other stages of the cycle, and that the oestradiol-induced cytokine microenvironment is significantly attenuated by progesterone. A continuously fluctuating cytokine microenvironment in the mammary gland presumably regulates the phenotypes of resident leukocytes and may affect mammary gland cancer susceptibility. PMID- 25138708 TI - "Old" metal oxide affinity chromatography as "novel" strategy for specific capture of cis-diol-containing compounds. AB - The metal oxide affinity chromatography (MOAC) materials have been extensively used for extraction of phosphate compounds in the past decade. Actually, some of these materials also possess adsorption affinity towards cis-diol-containing compounds, which was seldom explored in separation field so far. Here we present the proof-of-concept study to evaluate the feasibility of expanding MOAC for specific capture of cis-diol biomolecules. Benefitting from the high commercialisation of the metal oxide materials, such MOAC strategy possesses several advantages, like synthesis-free, low cost and high expandability. Firstly, the recognition of adenosine against 2'-deoxyadenosine was performed using zirconium oxide and cerium oxide, two typical commercial MOAC materials. The results showed that efficient adsorption and elution could be achieved easily by pH switching from basic to acidic. The isotherm curves demonstrated the adsorption process fitted well with Freundlich isotherm model and was spontaneous at room temperature (DeltaG(0)<0) with an exothermic nature (DeltaH(0)<0). Afterwards, the highly efficient and selective enrichment of various model cis diol biomolecules, including ribonucleosides, glycopeptides and glycoproteins, was achieved using this MOAC strategy. Finally, the endogenous ribonucleosides and modified ribonucleosides were successfully purified from human urine sample, which demonstrated the potential application of MOAC materials in the enrichment of target compounds from complex biological samples. Besides the excellent performance of extraction for cis-diol-containing compounds, equally important is that these materials are commercially available with low cost, which makes the MOAC a promising strategy for the study of cis-diol biomolecules in metabolomics and proteomics. PMID- 25138709 TI - Sodalis glossinidius prevalence and trypanosome presence in tsetse from Luambe National Park, Zambia. AB - BACKGROUND: Tsetse flies are the biological vectors of African trypanosomes, the causative agents of sleeping sickness in humans and nagana in animals. The tsetse endosymbiont Sodalis glossinidius has been suggested to play a role in tsetse susceptibility to infection. Here we investigate the prevalence of African trypanosomes within tsetse from the Luambe National Park, Zambia and if there is an association between S. glossinidius and presence of trypanosomes within the tsetse examined. METHODS: Tsetse representing three species (Glossina brevipalpis, Glossina morsitans morsitans and Glossina pallidipes), were sampled from Luambe National Park, Zambia. Following DNA extraction, PCR was used to examine the tsetse for presence of trypanosomes and the secondary endosymbiont S. glossinidius. RESULTS: S. glossinidius infection rates varied significantly between tsetse species, with G. brevipalpis (93.7%) showing the highest levels of infection followed by G. m. morsitans (17.5%) and G. pallidipes (1.4%). ITS-PCR detected a wide variety of trypanosomes within the tsetse that were analysed. Significant differences were found in terms of trypanosome presence between the three tsetse species. A high proportion of G. m. morsitans were shown to carry T. brucei s.l. DNA (73.7%) and of these around 50% were positive for Trypanosoma brucei rhodesiense. T. vivax, T. godfreyi, T. simiae, T. simiae Tsavo and T. congolense were also detected. No association was found between the occurrence of S. glossinidius and the presence of trypanosome DNA in any of the three tsetse species tested. CONCLUSION: The current work shows that T. b. rhodesiense was circulating in Luambe National Park, representing a risk for people living in the park or surrounding area and for tourists visiting the park. The differences in trypanosome DNA presence observed between the different tsetse species tested may indicate host feeding preferences, as the PCR will not discriminate between a fly with an active/resident infection compared to a refractory fly that has fed on an infected animal. This makes it difficult to establish if S. glossinidius may play a role in the susceptibility of tsetse flies to trypanosome infection. PMID- 25138710 TI - IMAGING DIAGNOSIS--URINARY BLADDER DUPLICATION IN A CAT. AB - A female kitten presented for chronic, intermittent, antibiotic-responsive urinary incontinence and chronic kidney disease. Abdominal ultrasound identified bilateral pelvic/ureteral dilation and three closely apposed thin-walled fluid filled structures in the caudal abdomen, extending toward the pelvic inlet. Excretory urography and negative contrast cystography identified contrast medium accumulation from the dilated ureters into two tubular soft tissue masses of the caudal abdomen, with subsequent gradual filling of a more cranially located urinary bladder. A retrograde vaginocystourethrogram identified a normal uterus, normal vagina, and a single urethra continuous with the cranially located urinary bladder. Antemortem diagnosis was suspicious for bilateral ectopic ureteroceles. Postmortem diagnosis, 35 months following initial presentation, determined the fluid-filled masses to have abundant smooth muscle in the wall, including a muscularis mucosa connected by a common ostium, consistent with urinary bladder duplication. Urinary bladder duplication should be included as a differential diagnosis in cats with these clinical and imaging characteristics. In this case, differentiation of ectopic ureterocele from urinary bladder duplication required histological confirmation. PMID- 25138711 TI - exo-Brevicomin biosynthetic pathway enzymes from the Mountain Pine Beetle, Dendroctonus ponderosae. AB - exoBrevicomin (exo-7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane) is an important semiochemical for a number of beetle species, including the highly destructive Mountain Pine Beetle (Dendroctonus ponderosae). It is also found in other insects and the African elephant. Despite its significance, very little is known about its biosynthesis. A recent microarray analysis implicated a small cluster of three D. ponderosae genes in exo-brevicomin biosynthesis, two of which had identifiable open reading frames (Aw et al., 2010; BMC Genomics 11:215). Here we report further expression profiling of two genes in that cluster and functional analysis of their recombinantly-produced enzymes. One encodes a short chain dehydrogenase that used NAD(P)(+) as a co-factor to catalyze the oxidation of (Z)-6-nonen-2-ol to (Z)-6-nonen-2-one. We therefore named the enzyme (Z)-6 nonen-2-ol dehydrogenase (ZnoDH). The other encodes the cytochrome P450, CYP6CR1, which epoxidized (Z)-6-nonen-2-one to 6,7-epoxynonan-2-one with very high specificity and substrate selectivity. Both the substrates and products of the two enzymes are intermediates in the exo-brevicomin biosynthetic pathway. Thus, ZnoDH and CYP6CR1 are enzymes that apparently catalyze the antepenultimate and penultimate steps in the exo-brevicomin biosynthetic pathway, respectively. PMID- 25138712 TI - Immunochemical quantification of cynomolgus CYP2J2, CYP4A and CYP4F enzymes in liver and small intestine. AB - 1. An increasing number of studies have indicated the roles of CYP4 proteins in drug metabolism; however, CYP4 expression has not been measured in cynomolgus monkeys, an important animal species for drug metabolism studies. 2. In this study, cynomolgus CYP4A11, CYP4F2/3, CYP4F11 and CYP4F12, along with CYP2J2, were immunoquantified using selective antibodies in 28 livers and 35 small intestines, and their content was compared with CYP1A, CYP2A, CYP2B6, CYP2C9/19, CYP2D, CYP2E1, CYP3A4 and CYP3A5, previously quantified. 3. In livers, CYP2J2, CYP4A11, CYP4F2/3, CYP4F11 and CYP4F12, varied 1.3- to 4.3-fold, represented 11.2, 14.4, 8.0, 2.7 and 0.3% of total immunoquantified CYP1-4 proteins, respectively. 4. In small intestines, CYP2J2, CYP4F2/3, CYP4F11 and CYP4F12, varied 2.4- to 9.7-fold, represented 6.9, 36.4, 2.4 and 9.3% of total immunoquantified CYP1-4 proteins, respectively, making CYP4F the most abundant P450 subfamily in small intestines. CYP4A11 was under the detection limit in all of the samples analyzed. 5. Significant correlations were found in liver for CYP4A11 with lauric acid 11-/12 hydroxylation and for CYP4F2/3 and CYP4F11 with astemizole hydroxylation. 6. This study revealed the relatively abundant contents of cynomolgus CYP2J2, CYP4A11 and CYP4Fs in liver and/or small intestine, suggesting their potential roles for the metabolism of xenobitotics and endogenous substrates. PMID- 25138713 TI - Electrospun honeycomb as nests for controlled osteoblast spatial organization. AB - Honeycomb nanofibrous scaffolds were elaborated by electrospinning onto micro patterned collectors either with poly(epsilon-caprolactone) (PCL) or poly(D, L lactic acid) (PLA). The unimodal distribution of fiber diameters, observed for PLA, led to relatively flat scaffolds; on the other hand, the bimodal distribution of PCL fiber diameters significantly increased the relief of the scaffolds' patterns due to the preferential deposition of the thick fiber portions on the walls of the collector's patterns via preferential electrostatic interaction. Finally, a biological evaluation demonstrated the effect of the scaffolds' relief on the spatial organization of MG63 osteoblast-like cells. Mimicking hemi-osteons, cell gathering was observed inside PCL honeycomb nests with a size ranging from 80 to 360 um. PMID- 25138715 TI - New clinical practice guidelines on the classification, evaluation and management of childhood interstitial lung disease in infants: what do they mean? AB - The American Thoracic Society (ATS) recently published a clinical practice guideline regarding the classification, evaluation, and management of childhood interstitial lung disease in infancy (chILD). As disease entities among infants with ILD are often distinct from forms seen in older children and adults, the guideline encourages an age-based classification system and focuses on the diagnostic approach to neonates and infants <2 years of age. The guideline reviews current evidence and recommendations for the evaluation, relevant genetic studies, and management of symptomatic infants. Here, we summarize the ATS guideline, highlight the major concepts, and discuss future strategies aimed at addressing current gaps in knowledge. PMID- 25138714 TI - M1 and M2 macrophages: the chicken and the egg of immunity. AB - The purpose of this perspective is to describe a critical advance in understanding how immune responses work. Macrophages are required for all animal life: 'Inhibit' type macrophages in all animals (called M1) can rapidly kill pathogens, and are thus the primary host defense, and 'Heal' type macrophages (M2) routinely repair and maintain tissue integrity. Macrophages perform these activities in all animals without T cells, and also in T cell-deficient vertebrates. Although adaptive immunity can amplify macrophage polarization, the long-held notion that macrophages need to be 'activated' or 'alternatively activated' by T cells is incorrect; indeed, immunology has had it backward. M1/M2 type macrophages necessarily direct T cells toward Th1- or Th2-like activities, respectively. That such macrophage-innate activities are the central directing element in immune responses is a dramatic change in understanding how immune systems operate. Most important, this revelation is opening up whole new approaches to immunotherapy. For example, many modern diseases, such as cancer and atherosclerosis, may not display 'foreign' antigens. However, there are clear imbalances in M1/M2-type responses. Correcting such innate imbalances can result in better health. Macrophages are the chicken and the egg of immunity. PMID- 25138716 TI - Deep resequencing reveals allelic variation in Sesamum indicum. AB - BACKGROUND: Characterization of genome-wide patterns of allelic variation and linkage disequilibrium can be used to detect reliable phenotype-genotype associations and signatures of molecular selection. However, the use of Sesamum indicum germplasm for breeding is limited by the lack of polymorphism data. RESULTS: Here we describe the massively parallel resequencing of 29 sesame strains from 12 countries at a depth of >= 13-fold coverage for each of the samples tested. We detected an average of 127,347 SNPs, 17,961 small InDels, and 9,266 structural variants per sample. The population SNP rate, population diversity (pi) and Watterson's estimator of segregating sites (thetaw) were estimated at 8.6 * 10-3, 2.5 * 10-3 and 3.0 * 10-3 bp-1, respectively. Of these SNPs, 23.2% were located within coding regions. Polymorphism patterns were nonrandom among gene families, with genes mediating interactions with the biotic or abiotic environment exhibiting high levels of polymorphism. The linkage disequilibrium (LD) decay distance was estimated at 150 kb, with no distinct structure observed in the population. Phylogenetic relationships between each of the 29 sesame strains were consistent with the hypothesis of sesame originating on the Indian subcontinent. In addition, we proposed novel roles for adenylate isopentenyltransferase (ITP) genes in determining the number of flowers per leaf axil of sesame by mediating zeatin biosynthesis. CONCLUSIONS: This study represents the first report of genome-wide patterns of genetic variation in sesame. The high LD distance and abundant polymorphisms described here increase our understanding of the forces shaping population-wide sequence variation in sesame and will be a valuable resource for future gene-phenotype and genome-wide association studies (GWAS). PMID- 25138717 TI - Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats. AB - Alcoholism is a chronic relapsing disorder with consequences on health and that requires more effective treatments. Among alternative therapies, the therapeutic potential of the non-competitive N-methyl-D-aspartate receptor antagonist memantine has been suggested. Despite promising results, its efficiency in the treatment of alcoholism remains controversial. Currently, there is no pre clinical data regarding its effects on the motivation for ethanol in post dependent (PD) animals exposed to intermittent ethanol vapor, a validated model of alcoholism. Thus, the objectives of this study were to evaluate the effects of acute injections of memantine (0, 12.5, 25 and 50 mg/kg) on operant ethanol self administration in non-dependent (ND) and PD rats tested either during acute withdrawal or relapse after protracted abstinence. Our results showed that memantine (25 mg/kg) abolished ethanol self-administration in ND rats and reduced by half the one of PD rats during acute withdrawal. While this effect was observed only 6 hours after treatment in ND rats, it was long lasting in PD rats (at least 30 hours after injection). Furthermore, our results indicated that memantine did not modify the breaking point for ethanol. This suggests that memantine probably act by potentiating the pharmacological effect of ethanol but not by reducing motivation for ethanol. Finally, memantine was also ineffective in reducing relapse after protracted abstinence. Altogether, our pre-clinical results highlighted a potential therapeutic use of memantine that may be used as a replacement therapy drug but not as relapse-preventing drug. PMID- 25138718 TI - Rapid evolution of adaptive niche construction in experimental microbial populations. AB - Many species engage in adaptive niche construction: modification of the local environment that increases the modifying organism's competitive fitness. Adaptive niche construction provides an alternative pathway to higher fitness, shaping the environment rather than conforming to it. Yet, experimental evidence for the evolutionary emergence of adaptive niche construction is lacking, leaving its role in evolution uncertain. Here we report a direct observation of the de novo evolution of adaptive niche construction in populations of the bacteria Pseudomonas fluorescens. In a laboratory experiment, we allowed several bacterial populations to adapt to a novel environment and assessed whether niche construction evolved over time. We found that adaptive niche construction emerged rapidly, within approximately 100 generations, and became ubiquitous after approximately 400 generations. The large fitness effect of this niche construction was dominated by the low fitness of evolved strains in the ancestrally modified environment: evolved niche constructors were highly dependent on their specific environmental modifications. Populations were subjected to frequent resetting of environmental conditions and severe reduction of spatial habitat structure, both of which are thought to make adaptive niche construction difficult to evolve. Our finding that adaptive niche construction nevertheless evolved repeatably suggests that it may play a more important role in evolution than generally thought. PMID- 25138719 TI - Cross-resistance and baseline susceptibility of Mediterranean strains of Bemisia tabaci to cyantraniliprole. AB - BACKGROUND: The whitefly Bemisia tabaci Gennadius is a severe pest in many field and greenhouse crops worldwide and has developed resistance to insecticides from most chemical classes. The ease with which this pest develops resistance makes it essential to incorporate new compounds with different modes of action and no cross-resistance with those previously used into insecticide resistance management strategies. To that end, the systemic effect of the new diamide cyantraniliprole was tested with multiresistant, selected and field populations of Q-biotype B. tabaci from the Mediterranean area. RESULTS: Bioassays with multiresistant and laboratory-selected populations indicated no cross-resistance to cyantraniliprole in the B. tabaci strains exhibiting resistance to other insecticides. The LC50 values for nymphs from 14 field populations varied between 0.011 and 0.116 mg L(-1), a 10.5-fold natural variability. The LC50 values for adults from three strains ranged from 0.060 to 0.096 mg L(-1). CONCLUSION: These baseline data will be helpful for monitoring future potential shifts in susceptibility to cyantraniliprole in Mediterranean whitefly populations within an IRM programme. Cyantraniliprole may play an important role in mitigating insecticide resistance in B. tabaci because of its high efficacy and its lack of cross-resistance to other insecticides, even in multiresistant Q-biotype populations collected from a highly problematic insecticide resistance area. PMID- 25138720 TI - Recanalization of chronic total occlusions of the superior mesenteric artery in patients with chronic mesenteric ischemia: technical and clinical outcomes. AB - PURPOSE: To evaluate the safety and outcomes of endovascular recanalization of chronic total occlusions (CTOs) of the superior mesenteric artery (SMA) in patients with chronic mesenteric ischemia (CMI). MATERIALS AND METHODS: A single institution retrospective review was performed of 47 consecutive patients (18 male, 29 female) who underwent endovascular stent placement for CTOs of the SMA between February 2006 and November 2012. All patients had symptoms of CMI. Procedural and follow-up data were collected for assessment of technical success, safety, and outcome. RESULTS: Technical success was achieved in 41 of 47 patients (87%). Forty-two of the 47 procedures were performed from a femoral approach. Fifteen patients underwent concurrent revascularization of the celiac artery. All patients who underwent successful recanalization reported symptomatic improvement. Kaplan-Meier analysis revealed primary freedom from symptomatic recurrence of 95% at 12 months and 78% at 24 months. Symptomatic recurrence was observed in seven patients, all of whom underwent successful assisted or secondary endovascular procedures. Secondary freedom from symptomatic recurrence rates were 100% at 12 months and 88% 24 months. There were three (7%) minor access-related complications and no major complications. CONCLUSIONS: Endovascular stent-assisted recanalization of chronic SMA occlusions is safe and effective, with an acceptable rate of technical success and excellent midterm clinical outcomes. PMID- 25138721 TI - Detection of potentially skin sensitizing hydroperoxides of linalool in fragranced products. AB - On prolonged exposure to air, linalool can form sensitizing hydroperoxides. Positive hydroperoxide patch tests in dermatitis patients have frequently been reported, but their relevance has not been established. Owing to a lack of analytical methods and data, it is unclear from which sources the public might be exposed to sufficient quantities of hydroperoxides for induction of sensitization to occur. To address this knowledge gap, we developed analytical methods and performed stability studies for fine fragrances and deodorants/antiperspirants. In parallel, products recalled from consumers were analysed to investigate exposure to products used in everyday life. Liquid chromatography-mass spectrometry with high mass resolution was found to be optimal for the selective and sensitive detection of the organic hydroperoxide in the complex product matrix. Linalool hydroperoxide was detected in natural linalool, but the amount was not elevated by storage in a perfume formulation exposed to air. No indication of hydroperoxide formation in fine fragrances was found in stability studies. Aged fine fragrances recalled from consumers contained a geometric mean linalool concentration of 1,888 MUg/g and, corrected for matrix effects, linalool hydroperoxide at a concentration of around 14 MUg/g. In antiperspirants, we detected no oxidation products. In conclusion, very low levels of linalool hydroperoxide in fragranced products may originate from raw materials, but we found no evidence for oxidation during storage of products. The levels detected are orders of magnitude below the levels inducing sensitization in experimental animals, and these results therefore do not substantiate a causal link between potential hydroperoxide formation in cosmetics and positive results of patch tests. PMID- 25138722 TI - Characterizing Pluripotent Stem Cells Using the TaqMan(r) hPSC Scorecard(TM) Panel. AB - Rapid technological developments for the efficient generation of footprint-free induced pluripotent stem cells (iPSC) enabled the creation of patient-specific iPSC for downstream applications in drug discovery and regenerative medicine. However, the large number of iPSCs, generated from diverse genetic backgrounds using various methods and culture conditions, created a steep challenge for rapid characterization and a demand for standardized methods. Current methods rely on a combination of in vitro and in vivo cellular analyses based on the expression of markers of self-renewal and the ability of the cells to differentiate into cell types representative of the three germ layers as a confirmation of functional pluripotency. These methods, though informative and extensively used, are not ideal for parallel analyses of large numbers of samples and hence not amenable to high-throughput environments. Recently, genetic and epigenetic expression signatures were used to define and confirm cell states, thus providing a surrogate molecular assay that can potentially replace complex in vivo cellular assays such as teratoma formation. In this chapter, we describe a molecular assay for rapid characterization and standardization of pluripotent stem cells. The TaqMan((r)) hPSC ScorecardTM Panel is a comprehensive gene expression real-time PCR assay that consists of 94 individual q-PCR assays comprised of a combination of control, housekeeping, self-renewal, and lineage-specific genes. The resulting expression data set is analyzed using cloud-based analysis software that compares the expression pattern against a reference standard composed of multiple functionally validated ESC and iPSC lines. This system was successfully used to test several ESC and iPSC lines in their undifferentiated states to confirm their signatures of self renewal, as well as their terminally differentiates states, via spontaneous differentiation and directed differentiation into specific lineages, to determine the lines' differentiation potential. This genetic analysis tool, together with the flexibility to utilize varying sample inputs and preparation methods, provides a rapid method to confirm functional pluripotency of ESCs and iPSCs. PMID- 25138723 TI - GMP-compliant human adipose tissue-derived mesenchymal stem cells for cellular therapy. AB - Stem cells, which can be derived from different sources, demonstrate promising therapeutic evidences for cellular therapies. Among various types of stem cell, mesenchymal stem cells are one of the most common stem cells that are used in cellular therapy. Human subcutaneous adipose tissue provides an easy accessible source of mesenchymal stem cells with some considerable advantages. Accordingly, various preclinical and clinical investigations have shown enormous potential of adipose-derived stromal cells in regenerative medicine. Consequently, increasing clinical applications of these cells has elucidated the importance of safety concerns regarding clinical transplantation. Therefore, clinical-grade preparation of adipose-derived stromal cells in accordance with current good manufacturing practice guidelines is an essential part of their clinical applications to ensure the safety, quality, characteristics, and identity of cell products. Additionally, GMP-compliant cell manufacturing involves several issues to provide a quality assurance system during translation from the basic stem cell sciences into clinical investigations and applications. On the other hand, advanced cellular therapy requires extensive validation, process control, and documentation. It also evidently elucidates the critical importance of production methods and probable risks. Therefore, implementation of a quality management and assurance system in accordance with GMP guidelines can greatly reduce these risks particularly in the higher-risk category or "more than minimally manipulated" products. PMID- 25138724 TI - Interstitial diffusion and the relationship between compartment modelling and multi-scale spatial-temporal modelling of (18)F-FLT tumour uptake dynamics. AB - Tumour cell proliferation can be imaged via positron emission tomography of the radiotracer 3'-deoxy-3'-18F-fluorothymidine (18F-FLT). Conceptually, the number of proliferating cells might be expected to correlate more closely with the kinetics of 18F-FLT uptake than with uptake at a fixed time. Radiotracer uptake kinetics are standardly visualized using parametric maps of compartment model fits to time-activity-curves (TACs) of individual voxels. However the relationship between the underlying spatiotemporal accumulation of FLT and the kinetics described by compartment models has not yet been explored. In this work tumour tracer uptake is simulated using a mechanistic spatial-temporal model based on a convection-diffusion-reaction equation solved via the finite difference method. The model describes a chain of processes: the flow of FLT between the spatially heterogeneous tumour vasculature and interstitium; diffusion and convection of FLT within the interstitium; transport of FLT into cells; and intracellular phosphorylation. Using values of model parameters estimated from the biological literature, simulated FLT TACs are generated with shapes and magnitudes similar to those seen clinically. Results show that the kinetics of the spatial-temporal model can be recovered accurately by fitting a 3 tissue compartment model to FLT TACs simulated for those tumours or tumour sub volumes that can be viewed as approximately closed, for which tracer diffusion throughout the interstitium makes only a small fractional change to the quantity of FLT they contain. For a single PET voxel of width 2.5-5 mm we show that this condition is roughly equivalent to requiring that the relative difference in tracer uptake between the voxel and its neighbours is much less than one. PMID- 25138725 TI - The diagnosis of and treatment recommendations for anxiety disorders. AB - BACKGROUND: Anxiety disorders (panic disorder/agoraphobia, generalized anxiety disorder, social phobia, and specific phobias) are the most common mental illnesses. For example, the 12-month prevalence of panic disorder/agoraphobia is 6%. METHOD: This guideline is based on controlled trials of psychotherapy and pharmacotherapy, retrieved by a systematic search for original articles that were published up to 1 July 2013. Experts from 20 specialty societies and other organizations evaluated the evidence for each treatment option from all available randomized clinical trials and from a synthesis of the recommendations of already existing international and German guidelines. RESULTS: 403 randomized controlled trials were evaluated. It was concluded that anxiety disorders should be treated with psychotherapy, psychopharmacological drugs, or both. Response rates to initial treatment vary from 45% to 65%. Cognitive behavioral therapy is supported by higher-level evidence than any other psychotherapeutic technique. Psychodynamic therapy is recommended as a second-line treatment. Among anxiolytic drugs, the agents of first choice are selective serotonin reuptake inhibitors and serotoninnorepinephrine reuptake inhibitors. The patient's preference should be considered in the choice of treatment. Drug treatment should be continued for 6 to 12 months after remission. If psychotherapy or drug treatment is not adequately effective, then the treatment should be switched to the other form, or to a combination of both. CONCLUSION: The large amount of data now available from randomized controlled trials permits the formulation of robust evidence-based recommendations for the treatment of anxiety disorders. Future work should more closely address the necessary duration of psychotherapy and the efficacy of combined psychotherapy and drug treatment. PMID- 25138728 TI - Incomplete description. PMID- 25138729 TI - Critical additions required. PMID- 25138727 TI - Patients with cancer of unknown primary: a retrospective analysis of 223 patients with adenocarcinoma or undifferentiated carcinoma. AB - BACKGROUND: Cancer of unknown primary (CUP) now accounts for 2-3% of all fatal cases of cancer in Germany. Histologically, most of these tumors are either adenocarcinoma or undifferentiated carcinoma. Scant data on their clinical features and prognosis are now available, and the published survival times are highly variable. In this article, we document and analyze our own experience with CUP to date. METHOD: We took all 223 patients with CUP (adenocarcinoma or undifferentiated carcinoma) whom we saw in our CUP clinic from 2006 to 2010 as an unaltered sample for retrospective analysis of clinical data and overall survival. We performed the analysis with Kaplan-Meier plotting, log-rank testing, and Cox regression. RESULTS: With a median follow-up time of 32.9 months, the median survival from the time of diagnosis was 16.5 months. Metastases were most commonly found in the lymph nodes, followed by the liver, bones, and lungs. The main pre-treatment prognostic variables that remained significant after adjustment for multiple testing were the Eastern Cooperative Oncology Group (ECOG) score for overall state of health and the number of organ systems involved. These variables were used to construct a practice-oriented risk stratification. CONCLUSION: In patients with adeno- or undifferentiated CUP syndrome, the ECOG score and the number of organ systems involved are important risk factors. PMID- 25138726 TI - Abdominal surgery in pregnancy--an interdisciplinary challenge. AB - BACKGROUND: Abdominal operations are performed during ca. 2% of all pregnancies. They represent an unusual situation not only for the patient, but also for the involved surgeons and anesthesiologists. Appendectomy, followed by cholecystectomy are the two most common types of operation performed during pregnancy. Special questions arise with regard to the peri- and intraoperative management and the optimal surgical approach. METHOD: This review is based on pertinent articles retrieved by a selective search in the PubMed database. RESULTS: The question of laparoscopy versus laparotomy during pregnancy has been addressed to date only in case series and a few meta-analyses. Two meta-analyses have shown a significantly higher rate of miscarriage after laparoscopic, compared to open, appendectomy (relative risk [RR] 1.91, 95% confidence interval [CI] 1.31-2.77). The risk of preterm birth is also somewhat higher after laparoscopic appendectomy according to one meta-analysis on this subject (RR 1.44, 95% CI 0.78-1.76), but significantly lower according to another meta analysis (2.1% vs. 8.1%, p<0.0001). For cholecystectomy, laparoscopy was associated with a lower miscarriage rate than laparotomy (1 in 89 cases, versus 2 in 69 cases), but with a somewhat higher preterm birth rate (6 in 89 cases, versus 2 in 69 cases). Delay or non-performance of surgery in a patient with appendicitis or cholecystitis can lead to additional hospitalizations, a higher miscarriage rate, premature rupture of the membranes, and preterm birth. CONCLUSION: Laparoscopy in experienced hands is safe even during pregnancy, with the recognized advantages of minimally invasive surgery, yet it carries a higher miscarriage rate than laparotomy, with a comparable preterm birth rate. Before surgery, patients should be thoroughly informed about the operation they are about to undergo and the advantages and disadvantages of the available surgical approaches. PMID- 25138730 TI - Drugs can only affect symptoms. PMID- 25138731 TI - Large group of patients cannot be found. PMID- 25138732 TI - In reply. PMID- 25138733 TI - Mode of delivery and subsequent reproductive patterns. A national follow-up study. AB - OBJECTIVE: To investigate associations between mode of delivery and subsequent reproductive outcomes. DESIGN: Cohort study. POPULATION: Women with term singleton live births from 1987 to 2009. SETTING: Denmark, birth registration data. METHODS: Women with a first singleton delivery after 37 weeks were followed until the end of 2010, from a first birth to include subsequent live births. We used Cox's proportional hazards model stratified by parity to compare the likelihood for subsequent delivery according to mode of delivery at first and later births, estimating maternal age effects and lag time to next delivery. MAIN OUTCOME MEASURE: Likelihood of a subsequent live-born child by previous delivery mode. RESULTS: We identified 642,052 women with a first delivery. Compared with women with a non-instrumental vaginal delivery, delivering a child by elective cesarean section implied a 23% (95% CI 0.76-0.787) decreased likelihood for subsequent delivery. Emergency cesarean section meant 16% fewer (95% CI 0.84 0.85), and vaginal instrumental delivery 4% fewer subsequent deliveries (95% CI 0.95-0.96). Hazard ratios were largely unchanged after controlling for parity and year of birth. Small age-trends were seen, with hazard ratios affected by maternal age at birth. Delivery mode at first birth affected marginally the time lag until next birth. CONCLUSIONS: Fecundity, measured as likelihood of a successive live-born child, varied with mode of delivery at the first and also subsequent births. A first or later delivery by cesarean section implied decreased likelihood of subsequent delivery compared with women with a first vaginal birth. PMID- 25138734 TI - A novel real-time CTL assay to measure designer T-cell function against HIV Env(+) cells. AB - BACKGROUND: To increase the immunosurveillance in HIV infection, we used retroviral vectors expressing CD4-chimeric antigen receptors (CARs) to genetically modify autologous T cells and redirect CTL toward HIV. The CD4 extracellular domain targets envelope and the intracellular signaling domains activate T cells. The maC46 fusion inhibitor binds HIV and blocks viral replication. METHODS: We stimulated rhesus PBMCs with antibodies to CD3/CD28 and cotransduced T cells with CD4-CAR and maC46 vectors. CD4-CAR-transduced T cells were added to Env(+) 293T cells at E:T of 1:1. Killing of target cells was measured as reduced impedance. RESULTS: We observed gene expression in 60-70% of rhesus CD3(+) CD8(+) T cells with the individual vectors and in 35% of the cells with both vectors. CD4-CAR-transduced populations specifically killed Env(+) cells. CONCLUSIONS: In these studies, we showed that designer T cells were redirected to kill Env(+) cells. Control of viremia without HAART would revolutionize treatment for HIV patients. PMID- 25138735 TI - Efficient water-splitting device based on a bismuth vanadate photoanode and thin film silicon solar cells. AB - A hybrid photovoltaic/photoelectrochemical (PV/PEC) water-splitting device with a benchmark solar-to-hydrogen conversion efficiency of 5.2% under simulated air mass (AM) 1.5 illumination is reported. This cell consists of a gradient-doped tungsten-bismuth vanadate (W:BiVO4 ) photoanode and a thin-film silicon solar cell. The improvement with respect to an earlier cell that also used gradient doped W:BiVO4 has been achieved by simultaneously introducing a textured substrate to enhance light trapping in the BiVO4 photoanode and further optimization of the W gradient doping profile in the photoanode. Various PV cells have been studied in combination with this BiVO4 photoanode, such as an amorphous silicon (a-Si:H) single junction, an a-Si:H/a-Si:H double junction, and an a Si:H/nanocrystalline silicon (nc-Si:H) micromorph junction. The highest conversion efficiency, which is also the record efficiency for metal oxide based water-splitting devices, is reached for a tandem system consisting of the optimized W:BiVO4 photoanode and the micromorph (a-Si:H/nc-Si:H) cell. This record efficiency is attributed to the increased performance of the BiVO4 photoanode, which is the limiting factor in this hybrid PEC/PV device, as well as better spectral matching between BiVO4 and the nc-Si:H cell. PMID- 25138736 TI - Effects of supplementation with Heracleum persicum fruit extract on serum lipids in patients undergoing coronary angiography: a pilot trial. AB - Heracleum persicum Desf. Ex Fischer (Apiaceae) is a native medicinal plant in the Iranian traditional medicine and also a safe and common dietary spice. The present pilot study aimed to investigate the impact of supplementation with H. persicum fruits on serum lipid concentrations in a group of patients with minimal coronary artery disease. Subjects who were diagnosed with <50% luminal narrowing in any of the major coronary arteries in coronary angiography were recruited for this trial and were randomized to receive either H. persicum hydroalcoholic fruit extract (n=15; 300 mg/day) or placebo (n=12) for a period of 6 months. Serum concentrations of total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides were measured at baseline and at the end of study. No significant difference in concentrations of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol was observed between H. persicum extract and placebo groups (p>0.05). However, serum triglycerides levels were reduced after H. persicum extract supplementation in a borderline significant manner (p=0.063). Short-term supplementation with H. persicum fruit extract might be used as an adjunctive treatment for patients with hypertriglyceridemia. PMID- 25138737 TI - Alternative treatment of stereotactic cyst aspiration and radiosurgery for cystic brain metastases. AB - BACKGROUND: Surgical removal is the first choice of treatment for large cystic brain metastases. However, some patients cannot undergo surgical resection due to their general condition and/or the tumor location. AIMS: In this study, we investigated the feasibility and safety of stereotactic cyst aspiration and gamma knife radiosurgery (GKR) as an alternative treatment for these lesions and followed the volumetric changes in cystic and solid portions. METHODS: Between February 2005 and March 2012, a total of 24 patients underwent GKR after cyst aspiration for 29 cystic metastatic brain tumors. The median age was 60 years (range, 18-81). The number of male patients was 18 and that of female patients 6. Most of the patients were in class II (87.5%) based on the data of the Radiation Therapy Oncology Group using recursive partitioning analysis. We analyzed the changes in tumor volume, the local control rate, intracranial progression-free survival (PFS) and overall survival (OS). RESULTS: Before aspiration, the mean total tumor volume was 32.7 cm(3) (range, 12.1-103.3) and cystic volume was 18.6 cm(3) (range, 8-72.3). The mean duration of cyst drainage was 1 day (range, 1-2). The mean amount of aspiration was 16.8 cm(3) (range, 6-67.4). After aspiration, the total mean volume was 12.4 cm(3) (range, 3.7-38.1) and cystic volume was 2.0 cm(3) (range, 0.1-9.5). The nature of the cyst was serous in 18, serous and hemorrhagic in 3, and serous and necrotic in 8. The median prescription dose was 16 Gy (range, 14-20). There was no treatment-related complication. The local control rate was 58.6% (17/29). The median survival to local recurrence was 6.0 (+/-1.42) months. During the follow-up period, an Ommaya reservoir was placed in 3 patients. Insertion of an Ommaya reservoir and whole-brain radiotherapy (WBRT) or GKR were done in 2 patients, WBRT in 2, GKR in 1 and operation in 1. The median intracranial PFS and OS after intracranial metastasis was 5.2 (+/-0.42) and 6.8 (+/-0.38) months. CONCLUSIONS: Cyst aspiration and GKR were feasible and safe but not very efficient, which could be an alternative option for large cystic metastases in patients who could not expect longer survival time. PMID- 25138738 TI - Atrial electromechanical delay is impaired in patients with psoriasis. AB - OBJECTIVE: In this study, we aimed to investigate atrial electromechanical delay (EMD) in patients with psoriasis. SUBJECTS AND METHODS: A total of 43 patients with psoriasis (26 mild-moderate, 17 severe) and 17 healthy control subjects were enrolled. Patients with psoriasis were divided into two groups: the mild-moderate group and the severe group according to their psoriasis area severity index (PASI) scores. Atrial EMD was measured from the lateral mitral annulus and called 'PA lateral', from the septal mitral annulus, called 'PA septal', and from the right ventricle tricuspid annulus, called 'PA tricuspid'. Atrial EMD was defined as the time interval from the onset of atrial electrical activity (P wave on surface ECG) to the beginning of mechanical atrial contraction (late diastolic A wave). All three groups were compared with each other, and correlation analysis was performed to investigate the relationship between the PASI score and interatrial EMD. RESULTS: PA lateral was significantly higher in both the mild moderate psoriasis group and the severe psoriasis group compared to controls (69 +/- 12 and 78 +/- 13 vs. 60 +/- 6 ms; p = 0.001). Also, PA septal (63 +/- 11 vs. 53 +/- 6 ms; p = 0.005, post hoc analysis) and PA tricuspid (49 +/- 7 vs. 41 +/- 5 ms; p = 0.009, post hoc analysis) were significantly higher in the severe psoriasis group than in the control group. Correlation analysis revealed that the PASI score was well correlated with PA lateral (r = 0.520, p < 0.001), PA septum (r = 0.460, p = 0.002), interatrial EMD (r = 0.371, p = 0.014) and intra-atrial EMD (r = 0.393, p = 0.009). CONCLUSION: Atrial EMD was prolonged in patients with psoriasis. The measurement of atrial EMD might be used to determine the risk of development of AF in patients with psoriasis. PMID- 25138739 TI - Prototype of biliary drug-eluting stent with photodynamic and chemotherapy using electrospinning. AB - BACKGROUND: The combination of biliary stent with photodynamic and chemotherapy seemed to be a beneficial palliative treatment of unresectable cholangiocarcinoma. However, by intravenous delivery to the target tumor the distribution of the drug had its limitations and caused serious side effect on non-target organs. Therefore, in this study, we are going to develop a localized eluting stent, named PDT-chemo stent, covered with gemcitabine (GEM) and hematoporphyrin (HP). METHODS: The prototype of PDT-chemo stent was made through electrospinning and electrospraying dual-processes with an electrical charge to cover the stent with a drug-storing membrane from polymer liquid. The design of prototype used PU as the material of the backing layer, and PCL/PEG blends in different molar ratio of 9:1 and of 1:4 were used in two drug-storing layers with GEM and HP loaded respectively. RESULTS: The optical microscopy revealed that the backing layer was formed in fine fibers from electrospinning, while drug-storing layers, attributed to the droplets from electrospraying process. The covered membrane, the morphology of which was observed by scanning electron microscopy (SEM), covered the stent surface homogeneously without crack appearances. The GEM had almost 100% of electrosprayed efficiency than 70% HP loaded on the covered membrane due to the different solubility of drug in PEG/PCL blends. Drug release study confirmed the two-phased drug release pattern by regulating in different molar ratio of PEG/PCL blends polymer. CONCLUSIONS: The result proves that the PDT-chemo stent is composed of a first burst-releasing phase from HP and a later slow-releasing phase from GEM eluting. This two-phase of drug eluting stent may provide a new prospect of localized and controlled release treatment for cholangiocarcinoma disease. PMID- 25138740 TI - Quercetin reduces pluripotency, migration and adhesion of human teratocarcinoma cell line NT2/D1 by inhibiting Wnt/beta-catenin signaling. AB - Quercetin, a bioflavonoid found in plant foods, has a wide range of therapeutic effects. In order to examine the therapeutic potential of quercetin in teratocarcinoma, we used the human teratocarcinoma cell line NT2/D1 as an in vitro model. We have shown that quercetin inhibits the proliferation, adhesion and migration of NT2/D1 cells and downregulates the expression of pluripotency factors SOX2, Oct4 and Nanog. Our results further suggest that the anticancer effect of quercetin against human teratocarcinoma cells is mediated by targeting the canonical Wnt signaling pathway. Quercetin antagonized the Wnt/beta-catenin signaling pathway in NT2/D1 cells by inhibiting beta-catenin nuclear translocation and the consequent downregulation of beta-catenin-dependent transcription. These data suggest that quercetin as a potent inhibitor of Wnt signaling may be an effective therapeutic agent in cancers with aberrant activation of the Wnt pathway. PMID- 25138741 TI - Comprehensive three-dimensional analysis of right-sided aortic arch with multiple vascular anomalies. AB - BACKGROUND: Right-sided aortic arch is a rare congenital defect usually diagnosed incidentally in adults; it is often asymptomatic unless aneurismal disease develops. In half the cases, an aberrant left subclavian artery arises from a Kommerell's diverticulum; in these cases, congenital heart anomaly is very rarely present. CASE PRESENTATION: We report a case of incidentally-detected right-sided aortic arch with multiple vascular anomalies including left subclavian artery originating from a Kommerell's diverticulum, supra-sinus origin of coronary arteries and coronary arteriovenous fistula. CONCLUSION: Through comprehensive 3 dimensional reconstruction of the aortic arch and surrounding structures we defined anatomical relationships, which is useful for follow-up and treatment. PMID- 25138742 TI - Amblyopia and the H Barry Collin research medal. PMID- 25138743 TI - Why are we still fitting reusable soft contact lenses? PMID- 25138744 TI - The tear ferning test: a simple clinical technique to evaluate the ocular tear film. AB - A healthy tear film is very important for many major functions of the ocular surface. Dry eye disease is a significant clinical problem that needs to be solved but the poor correlation between clinical signs and reported symptoms makes it difficult for the clinician to apply a scientific basis to his clinical management. The problem is compounded by the difficulties of evaluating the tear film due to its transparency, small volume and complex composition. Practical insight into tear film composition would be very useful to the clinician for patient diagnosis and treatment but detailed analysis is restricted to expensive, laboratory-based systems. There is a pressing need for a simple test. The tear ferning test is a laboratory test but it has the potential to be applied in the clinic setting to investigate the tear film in a simple way. Drying a small sample of tear fluid onto a clean, glass microscope slide produces a characteristic crystallisation pattern, described as a 'tear fern'. This test is currently not widely used because of some limitations that need to be overcome but several studies have demonstrated its potential. Such limitations need to be resolved so that tear ferning could be used in the clinic setting to assess the tear film. PMID- 25138745 TI - Post-cataract surgery diplopia: aetiology, management and prevention. AB - Diplopia is an infrequent but distressing adverse outcome after uncomplicated cataract surgery. Many factors may contribute to the occurrence of this problem, including prolonged sensory deprivation resulting in disruption of sensory fusion, paresis of one or more extraocular muscles, myotoxic effects of local anaesthesia, optical aberrations (for example, aniseikonia) and pre-existing disorders (for example, thyroid orbitopathy). The purpose of this review is to present the aetiology and clinical features of diplopia after cataract surgery and to discuss the possible modalities for the prevention and treatment of this frustrating complication. PMID- 25138746 TI - Comparison of four different binocular balancing techniques. AB - BACKGROUND: Several techniques of balancing have been proposed for the equalisation of the accommodative state between the two eyes. This study was designed to compare the results of different balancing techniques. METHODS: In this study, 60 subjects participated. Refractive errors were determined using retinoscopy and results were refined with monocular subjective refraction to determine the ametropia with the most plus lens and this was used as the starting point for balancing. The monocular refractive values before the balance were the same for all balancing procedures. Four balancing techniques, three dissociated and one associated, (alternate occlusion, prism-dissociated blur balance, prism dissociated red-green balance and Humphriss immediate contrast method) were used for the final refinement of findings. Results were analysed as the interocular spherical difference (IOSD) after the completion of each balance procedure. The interocular spherical difference was defined as the right eye sphere minus the left eye sphere. Data were analysed in SPSS.17 software using the paired samples t-test, the Pearson correlation, repeated measures ANOVA and 'intraclass correlation coefficient' (ICC) tests. RESULTS: The lowest mean difference was related to the alternate occlusion with the prism-dissociated blur balance techniques. The lowest 95% limits of agreement were related to the prism dissociated red-green balance with the Humphriss immediate contrast methods. The highest correlation and intraclass correlation coefficient were related to the prism-dissociated red-green balance with the Humphriss immediate contrast methods. CONCLUSIONS: The four balancing methods yield very similar results. The balance findings with red-green dissociated method and the Humphriss immediate contrast technique can be considered interchangeable and the other pairs of comparisons very nearly so. PMID- 25138747 TI - Selection considerations when using a 'standard optometrist' to evaluate clinical performance of other eye-care personnel. AB - BACKGROUND: Selection of a standard professional is crucial for assessing the clinical performance of other eye-care personnel. This paper describes the selection considerations and the clinical competency assessment of two optometrists required to select a 'standard optometrist' (SO) for evaluating the clinical performance of vision technicians in India. METHODS: Two optometrists were short-listed from 21 optometrists who responded to an advertisement to be selected as a SO for the assessment of the performance of 24 vision technicians in rural vision centres. Each candidate optometrist performed a routine eye examination on 40 randomly selected, newly registered subjects in a tertiary hospital clinic. Their non-cycloplegic retinoscopic findings were compared with those of an experienced optometrist, while disease diagnoses were compared with the findings of an ophthalmologist. RESULTS: A comparison of retinoscopic findings showed that optometrist A produced retinoscopic values within +/-0.50 D agreement for the spherical equivalent (SE) 100 per cent of the time, while optometrist B obtained agreement 91.3 per cent of the time. Similarly, optometrist A's limits of agreement (SE = -0.63 to +0.45 D) and reproducibility limits (SE = 0.78 D) were better than those of optometrist B (SE = -0.98 to +0.70 D and SE =1.18 D, respectively). Optometrist A demonstrated 89.2 per cent sensitivity in detecting ocular pathology compared to 76.3 per cent by optometrist B. CONCLUSIONS: Optometrist A achieved consistent and reproducible retinoscopic findings as well as higher sensitivity in detecting ocular pathology and was selected as the SO for a study to assess the clinical performance of one year trained vision technicians. The concept of a SO calibrated against an ophthalmologist for disease detection and diagnosis and an experienced optometrist for retinoscopy is a useful approach for the evaluation of eye-care personnel. PMID- 25138748 TI - Prevalence of visual problems among stroke survivors in Hong Kong Chinese. AB - BACKGROUND: Stroke, a common cerebrovascular accident, usually results in various extents of functional disability. Extensive studies have shown that ocular and visual problems are common in patients with stroke. Unfortunately, current stroke rehabilitation programs rarely address stroke-related ocular and visual problems in Hong Kong. METHODS: To examine how visual impairment (for example, deterioration in visual acuity and restriction in visual field) affects the stroke population in Hong Kong, vision screening was conducted for post-stroke patients attending in-patient and out-patient stroke clinics at two hospitals. RESULTS: One hundred and thirteen stroke patients were recruited. The percentage of various aspects of visual problems in Hong Kong post-stroke patients was generally lower than that reported in Western countries; however, a high percentage of patients had deficits in oculomotor (53.1 per cent) and vergence functions (11.5 per cent), restrictions in binocular visual field (11.5 per cent) and impairment in visual acuity (worse than 0.30 logMAR, 29.8 per cent). Conversely, only a small proportion of patients noticed problems with their vision (for example, diplopia and blurry vision) through subjective reports. This revealed that many post-stroke patients had undetected or undiagnosed ocular and visual problems. Appropriate referral was given to patients with visual problems for further evaluation and treatment. CONCLUSION: Neglecting visual problems may impose deteriorating effect on patients' stroke rehabilitation and functional independence and lead to increased incidents of injury. To address this potential hindrance in rehabilitation, formal screening for visual problems in stroke patients in a rehabilitation setting is essential. PMID- 25138749 TI - Agreement study of keratometric values measured by Biograph/LENSTAR, auto-kerato refractometer and Pentacam: decision for IOL calculation. AB - BACKGROUND: The aim was to determine the agreement in keratometric readings measured with the Biograph/LENSTAR, the Pentacam and an auto-kerato-refractometer in a 40- to 64-year-old population. METHODS: This report is part of the first phase of the population-based Shahroud Cohort Eye Study. In virgin eyes, agreement among keratometry readings of three devices was examined in 7,260 eyes using the Bland-Altman method. The inter-device 95 per cent limits of agreement (95% LoA) and 95% confidence interval for upper and lower limits of agreement were calculated. Comparisons were made for keratometric readings of the flat and steep meridians as maximum keratometry (max-K), minimum keratometry (min-K) and their average (mean-K). RESULTS: Based on Biograph/LENSTAR measurements, averages of max-K, min-K and mean-K were 44.70 +/- 1.64, 43.87 +/- 1.54 and 44.28 +/- 1.58 D, respectively. The quantile-quantile plot revealed that all three variables had normal distributions in this population. Agreement between the Biograph/LENSTAR and the auto-kerato-refractometer (max-K difference: -0.03 D, 95% LoA: -0.81 to 0.75; min-K difference: -0.08 D, 95% LoA: -0.85 to 0.68) was better than the agreement between the Biograph/LENSTAR and the Pentacam (max-K difference: 0.50 D, 95% LoA: -3.24 to 4.25; min-K difference: 0.59 D, 95% LoA: -3.00 to 4.17). The agreement between the Pentacam and the auto-kerato-refractometer (max-K difference: 0.54 D, 95% LoA: -3.16 to 4.24; min-K difference: 0.66 D, 95% LoA: 0.77 to 0.53) was worse than the other two pairs. CONCLUSION: These three devices are not interchangeable in terms of keratometry for calculation of the intraocular lens power. Agreement between the Biograph/LENSTAR and the auto kerato-refractometer can be increased with regression models but this is not true in case of Biograph/LENSTAR and Pentacam. PMID- 25138750 TI - Professor Robert F Hess DSc PhD MSc DipOptom: awarded the H Barry Collin Research Medal for 2013. PMID- 25138751 TI - Acute macular neuroretinopathy: the evolution of the disease through the use of newer diagnostic modalities. PMID- 25138752 TI - Combined hamartoma of the retina and retinal pigment epithelium with hypo autofluorescence and cystic degeneration at the macula. PMID- 25138755 TI - Interventional magnetic resonance imaging-guided cell transplantation into the brain with radially branched deployment. AB - Intracerebral cell transplantation is being pursued as a treatment for many neurological diseases, and effective cell delivery is critical for clinical success. To facilitate intracerebral cell transplantation at the scale and complexity of the human brain, we developed a platform technology that enables radially branched deployment (RBD) of cells to multiple target locations at variable radial distances and depths along the initial brain penetration tract with real-time interventional magnetic resonance image (iMRI) guidance. iMRI guided RBD functioned as an "add-on" to standard neurosurgical and imaging workflows, and procedures were performed in a commonly available clinical MRI scanner. Multiple deposits of super paramagnetic iron oxide beads were safely delivered to the striatum of live swine, and distribution to the entire putamen was achieved via a single cannula insertion in human cadaveric heads. Human embryonic stem cell-derived dopaminergic neurons were biocompatible with the iMRI guided RBD platform and successfully delivered with iMRI guidance into the swine striatum. Thus, iMRI-guided RBD overcomes some of the technical limitations inherent to the use of straight cannulas and standard stereotactic targeting. This platform technology could have a major impact on the clinical translation of a wide range of cell therapeutics for the treatment of many neurological diseases. PMID- 25138756 TI - Sequential therapy with ranibizumab and dexamethasone intravitreal implant is better than dexamethasone monotherapy for macular oedema due to retinal vein occlusion. AB - PURPOSE: To evaluate the efficacy and safety of sequential therapy with ranibizumab followed by dexamethasone intravitreal implant compared with dexamethasone monotherapy for macular oedema (MO) secondary to retinal vein occlusion (RVO). METHODS: In this retrospective interventional study, the medical records of subjects with MO due to RVO who received either ranibizumab followed by dexamethasone intravitreal implant (Group 1) or dexamethasone-implant monotherapy (Group 2) were included. Primary outcome was the proportion of subjects who exhibited best-corrected visual acuity (VA) gain and resolution of MO within 6 months. RESULTS: Thirty-three eyes were included (17 in Group 1, 16 in Group 2). More subjects in Group 1 exhibited a VA gain of at least 0.5 (LogMAR units hereafter) than Group 2 (29% vs 0%, p=0.044). The speed of VA gain was greater in Group 1 (1.4+/-0.8 months vs 2.7+/-1.4 months, p=0.020). MO was controlled in more subjects in Group 1 at all measured time intervals, and this difference was statistically significant at 3 months and 4 months. Subjects with branch RVO experienced VA gain more rapidly if they were from Group 1 (p=0.023). CONCLUSIONS: Sequential therapy was found to be more effective than dexamethasone monotherapy in treating MO due to RVO. PMID- 25138757 TI - A comparison of methods used to evaluate mobility performance in the visually impaired. AB - PURPOSE: To compare three different approaches to measuring mobility performance when evaluating the visually impaired. METHODS: 488 participants, including 192 glaucoma, 112 age-related macular degeneration, 91 diabetic retinopathy and 93 healthy volunteers, completed the Assessment of Disability Related to Vision (ADREV) mobility course. The performance of participants on the mobility course was evaluated by noting errors made and time required for completion. Errors noted and time taken were compared using multivariate logistic regression to determine which measurement better differentiated patients with visual disease from healthy volunteers. Multivariate logistic regression was also used to evaluate the combined metric of ADREV errors divided by time to determine its ability to discriminate participants with visual disease from healthy volunteers. RESULTS: Errors noted and time taken while ambulating through the standardised mobility course shared a weak but statistically significant association (Pearson's r=0.36, p<0.05). After controlling for demographic and medical comorbidities, logistic regression analysis revealed that errors noted were better at discriminating individuals with visual disease from healthy volunteers (OR 2.8-4.9, 95% CI 1.5 to 10.3) compared with the time taken for mobility course completion (OR 1.1, 95% CI 1.0 to 1.2). These findings were consistent across all comparisons between healthy volunteers and participants with each type of visual impairment. Finally, the combined metric of ADREV errors divided by time was far more predictive of visual disease compared with either time taken or errors noted during mobility testing (OR 11.0-17.7, 95% CI 3.6 to 77.1). CONCLUSIONS: A validated scoring system based on errors is more effective when assessing visual disability during mobility testing than recording the time taken for course completion. The combined metric of ADREV errors noted divided by time taken was most predictive of all the methods used to evaluate visual disability during mobility testing. PMID- 25138758 TI - Comparative role of 20% cord blood serum and 20% autologous serum in dry eye associated with Hansen's disease: a tear proteomic study. AB - BACKGROUND: To compare the role of topically applied serum therapy with preservative-free artificial tear (AT) drops in patients with moderate to severe dry eye in Hansen's disease along with change in tear protein profile. METHODS: 144 consecutive patients were randomly divided into three groups. After a baseline examination of clinical parameters, each of the patients received designated modality of topical therapy six times a day for 6 weeks. Post treatment documentation of clinical parameters was done at 6 weeks, and then at 12 weeks after discontinuation of topical therapy. Analysis of three tear proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel electrophoresis) was done at baseline, at the first and second post-treatment visits. RESULTS: In the cord blood serum (CBS) group, except for McMonnies score and staining score, all other clinical parameters showed continued improvement in the first and second post-treatment analyses. In the autologous serum (ALS) group, all the clinical parameters except Schirmer's I showed significant improvement in the first post-treatment analysis .This was sustained at a significant level in the second analysis except for tear film break-up time (TBUT) and conjunctival impression cytology grading. In the AT group, all the parameters improved at a non-significant level except for TBUT in the first analysis. In the next analysis, apart from McMonnies score and TBUT, other clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme, lactoferrin levels improved in both post-treatment measurements (statistically insignificant).Total tear protein continued to increase at statistically significant levels in the first and second post-treatment analyses in the CBS group and at a statistically insignificant level in the ALS group. In the AT group, the three tear proteins continued to decrease in both the analyses. CONCLUSIONS: In moderate to severe dry eye in Hansen's disease, serum therapy in comparison with AT drops, improves clinical parameters and causes betterment in tear protein profile. TRIAL REGISTRATION NUMBER: CTRI/2013/07/003802. PMID- 25138759 TI - Cystoid macular oedema following Descemet membrane endothelial keratoplasty. AB - BACKGROUND: To determine the incidence and potential risk factors of cystoid macular oedema (CMO) following Descemet membrane endothelial keratoplasty (DMEK) with or without simultaneous cataract surgery. METHODS: In this study, 155 eyes of 88 patients suffering from Fuchs endothelial dystrophy (81%), bullous keratopathy (17.6%) or other corneal diseases (1.4%) underwent DMEK. 52% were pseudophacic (DMEK) and 48% received simultaneous cataract surgery (DMEK combined with cataract surgery (Triple-DMEK)) at the Eye Center at Albert Ludwigs University of Freiburg between May 2011 and June 2013. Spectral-domain optical coherence tomography (SD-OCT) was performed 6 weeks, 3 months and 6 months following (Triple-)DMEK and in unscheduled visits due to limited or decreased visual acuity. The medical records were reviewed for pre-existing comorbidities limiting visual acuity. Patients with a history of macular oedema were excluded. We estimated the incidence of CMO using the Kaplan-Meier method. Potential risk factors for CMO were analysed with a Cox regression analysis and Pearson's correlation. The Cox model included the following variables: patient age and axial length, simultaneous cataract surgery, rate of rebubbling, donor age and donor endothelial cell density. RESULTS: 13% of all eyes developed a single episode of CMO at the end of the follow-up. After 6 months, 13.3% of eyes following Triple-DMEK and 12.5% of eyes following DMEK showed CMO. There was a statistically significant correlation between CMO development and best spectacle corrected visual acuity. Long axial length had a protective effect on CMO development (HR=0.3; p=0.03). Under medical therapy, central foveal thickness decreased in all patients. CMO did not have a relevant effect on long-term visual acuity. CONCLUSIONS: CMO is a frequent complication following DMEK in phacic and pseudophacic eyes. The prognosis is excellent given medical treatment. We recommend regular SD-OCT monitoring during the first 6 months following DMEK. PMID- 25138760 TI - Inhibition by rebamipide of cytokine-induced or lipopolysaccharide-induced chemokine synthesis in human corneal fibroblasts. AB - BACKGROUND/AIMS: The dry-eye drug rebamipide has mucin secretagogue activity in and anti-inflammatory effects on corneal epithelial cells. Corneal stromal fibroblasts (transdifferentiated keratocytes) function as immune modulators in the pathogenesis of chronic ocular allergic inflammation and in innate immune responses at the ocular surface. The possible anti-inflammatory effects of rebamipide on human corneal stromal fibroblasts were examined. METHODS: Serum deprived cells were incubated for 1 h with rebamipide and then for various times in the additional absence or presence of cytokines or bacterial lipopolysaccharide (LPS). The release of chemokines into culture supernatants was determined with ELISAs. The intracellular abundance of chemokine mRNAs was quantitated by reverse transcription and real-time PCR analysis. Degradation of the nuclear factor kappaB (NFkappaB) inhibitor IkappaBalpha was detected by immunoblot analysis. RESULTS: Rebamipide suppressed the release of interleukin (IL)-8 and the upregulation of IL-8 mRNA induced by tumour necrosis factor alpha (TNF-alpha) or LPS in corneal fibroblasts. It also inhibited eotaxin-1 (CCL-11) expression at the protein and mRNA levels induced by the combination of TNF-alpha and IL-4. In addition, rebamipide attenuated the degradation of IkappaBalpha induced by TNF-alpha or LPS. CONCLUSIONS: Rebamipide inhibited the synthesis of chemokines by corneal fibroblasts in association with suppression of NFkappaB signalling. Rebamipide may therefore prove effective for the treatment of corneal stromal inflammation associated with allergy or bacterial infection. PMID- 25138761 TI - Accelerated versus standard corneal collagen crosslinking combined with same day phototherapeutic keratectomy and single intrastromal ring segment implantation for keratoconus. AB - AIM: To compare the results of same day transepithelial phototherapeutic keratectomy (t-PTK) and single inferior intracorneal ring segment (ICRS) combined with standard versus accelerated corneal collagen crosslinking (CXL) for keratoconus. METHODS: All consecutive progressive keratoconus eyes that underwent standard or accelerated CXL treatment preceded by same day t-PTK and placement of a single inferior ICRS and had 6 and 12 months of follow-up were reviewed retrospectively. Eyes were classified into two groups, the 'standard' and the 'accelerated' group, accordingly. Visual, refractive and topographic data prior to surgery and at 6 and 12 months post-treatment were analysed. RESULTS: Sixteen eyes were included in each of the standard and the accelerated groups. Mean patient age was 27.5+/-8.5 years and 30.5+/-10.7 years (p=0.38) in the standard and accelerated groups, respectively. There was a significant improvement in uncorrected distance visual acuity, refractive cylinder and all examined corneal parameters in both groups 12 months postsurgery. The corrected distance visual acuity and manifest refraction spherical equivalent showed a significant improvement after 12 months of follow-up only in the accelerated group. However, mean changes in all evaluated parameters did not differ significantly between the two groups. CONCLUSIONS: A combined treatment of accelerated CXL preceded by same day t-PTK and single ICRS is as effective as the combined treatment using standard CXL for visual rehabilitation in progressive keratoconus. PMID- 25138762 TI - In vivo confocal microscopic characterisation of the cornea in chronic graft versus-host disease related severe dry eye disease. AB - AIMS: To first describe in vivo confocal microscopic (IVCM) corneal findings in severe dry eye syndrome due to ocular chronic graft versus host disease (cGvHD) after allogeneic stem cell transplantation. METHODS: IVCM of the central cornea was performed in 12 prospectively recruited patients with severe ocular cGvHD associated dry eye syndrome and in six control patients with haematological malignancies without cGvHD. Within each examined corneal layer, at least three non-overlapping areas were selected for representative analysis. RESULTS: The number of sub basal nerve branches was markedly reduced in patients with cGvHD. Sub basal nerve morphology was characterised by increased tortuosity and reduced reflectivity. Accumulation of hyper-reflective extracellular matrix, significantly increased haze and increased keratocyte density were found in the anterior stroma of the study group. CONCLUSIONS: IVCM findings of the cornea in patients with severe ocular cGvHD include a rarefaction of the sub basal corneal nerve plexus and dense accumulation of hyper-reflective extracellular matrix in the anterior stroma. PMID- 25138764 TI - Two novel mutations including a large deletion of the SLC4A11 gene causing autosomal recessive hereditary endothelial dystrophy. PMID- 25138763 TI - Infectious involvement in a tertiary center pediatric uveitis cohort. AB - BACKGROUND/AIMS: Studies of uveitis in children have focused primarily on non infectious causes. To date, no systematic study of infectious uveitis in children has been conducted. We investigate the prevalence of infectious causes of uveitis in children and explore the diagnostic value of analysing aqueous humour. METHODS: Retrospective cohort study in a tertiary referral centre for paediatric uveitis. Medical records of 345 children with uveitis presenting from 1995 through 2010 were reviewed for infectious causes (by serology and aqueous humour analysis). RESULTS: A diagnosis of infectious uveitis was established in 60/345 (17%) children. The most prevalent pathogen was Toxoplasma gondii (36/60; 60%), followed by viral infections (18/60; 30%). The most prevalent viral pathogen was varicella-zoster virus (VZV), representing 7/18 (39%) children. Viral causes were less often bilateral than other infectious causes (p=0.04). Specific IgG serum levels determined in 42/60 (70%) patients, were positive in 41/42 (98%). Aqueous humour was analysed for 24/60 (40%) patients and was positive in 18/24 (75%). CONCLUSIONS: An infectious cause of uveitis was identified in 17% of children with uveitis. T gondii and VZV were the most prevalent pathogens. We recommend analysing the aqueous humour of every child with vision-threatening uveitis of undetermined origin. PMID- 25138765 TI - Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomised double-masked open-label clinical trial. AB - BACKGROUND/AIMS: To assess the efficacy and safety of oral azithromycin compared with oral doxycycline in patients with meibomian gland dysfunction (MGD) who had failed to respond to prior conservative management. METHODS: 110 patients (>12 years old) with MGD were randomly assigned to receive either oral 5-day azithromycin (500 mg on day 1 and then 250 mg/day) or 1-month doxycycline (200 mg/day). They also continued eyelid warming/cleaning and artificial tears. A score comprising five symptoms and seven signs (primary outcome) was recorded prior to treatment and at 1 week, and 1 and 2 months after treatment. Total score was the sum of both scores at each follow-up. Side effects were recorded and overall clinical improvement was categorised as excellent, good, fair or poor based on the percentage of change in the total score. RESULTS: Symptoms and signs improved significantly in both groups (p=0.001). While improvement of symptoms was not different between the groups, bulbar conjunctival redness (p=0.004) and ocular surface staining (p=0.01) were significantly better in the azithromycin group. The azithromycin group showed a significantly better overall clinical response (p=0.01). Mild gastrointestinal side effects were not significantly different between the groups except for the second visit, when the doxycycline group had significantly more side effects (p=0.002). CONCLUSIONS: Although both oral azithromycin and doxycycline improved the symptoms of MGD, 5-day oral azithromycin is recommended for its better effect on improving the signs, better overall clinical response and shorter duration of treatment. TRIAL REGISTRATION NUMBER: NCT01783860. PMID- 25138766 TI - Transpalpebral proton beam radiotherapy of choroidal melanoma. AB - BACKGROUND: Collateral damage to upper eyelid margin during proton beam radiotherapy (PBR) for choroidal melanoma may cause squamous metaplasia of the tarsal conjunctiva with keratinisation, corneal irritation, discomfort and, rarely, corneal perforation. We evaluated transpalpebral PBR as a means of avoiding collateral damage to the upper eyelid margin without increasing the risk of failure of local tumour control. METHODS: Retrospective study of consecutive patients who underwent PBR for choroidal melanoma between 1992 and 2007 at the Royal Liverpool University Hospital and the Douglas Cyclotron at Clatterbridge Cancer Centre, UK. RESULTS: Sixty-three patients were included in this study. Mean basal tumour diameter and tumour thickness were 11.8 mm and 3.6 mm, respectively. PBR mean beam range and modulation were 26.5 mm and 16.9 mm respectively. The eyelid margin was included in the radiation field in 15 (24%) eyes. The median follow-up was 2.5 years. Local tumour recurrence developed in 2 (3.2%) patients. In these two cases that developed tumour recurrence the transpalpebral treatment did not involve the eyelid margin. Six (9.5%) patients died of metastatic disease. No eyelid or ocular surface problems developed in any of the 48 patients who were treated without eyelid rim involvement, while 7 of the 15 patients with unavoidable irradiation of the eyelid rim developed some degree of madarosis. These seven patients all received more than 26.55 proton Gy to the eyelid margin. Symptoms, such as grittiness occurred in 12% of 48 patients without eyelid margin irradiation as compared with 53% of 15 patients whose lid margin was irradiated. CONCLUSIONS: Transpalpebral PBR of choroidal melanoma avoids eyelid and ocular surface complications without increasing failure of local tumour control. PMID- 25138767 TI - Severity of acute ocular involvement is independently associated with time to resolution of ocular disease in toxic epidermal necrolysis patients. AB - PURPOSE: Toxic epidermal necrolysis (TEN) is a severe, life-threatening mucocutaneous disorder that frequently involves the ocular surface. This study aims to investigate the natural history and resolution of acute ocular involvement in patients with TEN admitted to the intensive care unit (ICU). METHODS: Case notes of patients admitted to ICU with TEN at a tertiary referral centre in a 9-year period were retrospectively reviewed. Patients' characteristics, severity of ocular involvement, SCORTEN systemic severity score and treatment were correlated with resolution of ocular involvement and time to resolution. RESULTS: Nine out of 10 (90%) patients had ocular involvement with 4 graded as mild, 2 as moderate and 3 as severe. All had bilateral ocular disease. The median length of hospital stay was 28 days and the median time to resolution of ocular involvement was 19 days. Four out of 9 (44%) patients still had active ocular disease at the time of discharge. Only older age (p=0.032) and a milder grade of ocular disease (p=0.001) were significantly associated with resolution of ocular disease. In a multivariable Cox-regression model, only a milder grade of ocular disease remained independently associated with time to resolution of ocular disease (p=0.006). CONCLUSIONS: Grading of acute ocular disease severity does not reflect systemic disease severity and is significantly associated with resolution and time to resolution of ocular involvement in TEN. The high rate of ocular involvement in patients with TEN and relatively large proportion of patients with active disease on discharge reiterates the need for constant ophthalmological monitoring of these patients. PMID- 25138768 TI - Re: Ang et al: Descemet's stripping automated endothelial keratoplasty with anterior chamber intraocular lenses: complications and 3-year outcomes. PMID- 25138770 TI - Rationale and design of the Henry Ford Exercise Testing Project (the FIT project). AB - Although physical fitness is a powerful prognostic marker in clinical medicine, most cardiovascular population-based studies do not have a direct measurement of cardiorespiratory fitness. In line with the call from the National Heart Lung and Blood Institute for innovative, low-cost, epidemiologic studies leveraging electronic medical record (EMR) data, we describe the rationale and design of the Henry Ford ExercIse Testing Project (The FIT Project). The FIT Project is unique in its combined use of directly measured clinical exercise data retrospective collection of medical history and medication treatment data at the time of the stress test, retrospective supplementation of supporting clinical data using the EMR and administrative databases and epidemiologic follow-up for cardiovascular events and total mortality via linkage with claims files and the death registry. The FIT Project population consists of 69 885 consecutive physician-referred patients (mean age, 54 +/- 10 years; 54% males) who underwent Bruce protocol treadmill stress testing at Henry Ford Affiliated Hospitals between 1991 and 2009. Patients were followed for the primary outcomes of death, myocardial infarction, and need for coronary revascularization. The median estimated peak metabolic equivalent (MET) level was 10, with 17% of the patients having a severely reduced fitness level (METs < 6). At the end of the follow-up duration, 15.9%, 5.6%, and 6.7% of the patients suffered all-cause mortality, myocardial infarction, or revascularization procedures, respectively. The FIT Project is the largest study of physical fitness to date. With its use of modern electronic clinical epidemiologic techniques, it is poised to answer many clinically relevant questions related to exercise capacity and prognosis. PMID- 25138771 TI - Fabrication of collagen scaffolds impregnated with sago starch capped silver nanoparticles suitable for biomedical applications and their physicochemical studies. AB - The present investigation attempts at fabricating collagen-based scaffolds impregnated with sago starch capped silver nanoparticles (AgNPs), useful for biomedical applications, and aims at studying their physicochemical aspects. AgNPs synthesized through a chemical reduction method, capped using different concentrations of sago starch, are incorporated into collagen derived from fish scales, and lyophilized to form scaffolds. FT-IR spectra confirm and validate the interaction of sago starch capped AgNPs with collagen in the scaffolds. TGA and DSC results indicate enhanced thermal stability of collagen scaffolds impregnated with sago capped AgNPs compared to collagen alone. All the collagen scaffolds containing sago starch capped AgNPs show high tensile strength values for their use as wound dressing materials. Moreover, lower minimum inhibitory concentration values are obtained for the above capped AgNP collagen scaffolds, which indicate higher antibacterial activities compared to uncapped AgNPs tested against both gram positive and negative bacterial strains. The novelty is that the developed scaffolds are biodegradable and in vitro studies reveal them as biocompatible and suitable for tissue regeneration applications. PMID- 25138772 TI - Lactose-functionalized dendrimers arbitrate the interaction of galectin-3/MUC1 mediated cancer cellular aggregation. AB - By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we studied cancer cell aggregation in three different cell lines (A549, DU-145, and HT-1080) with galectin-3. We found that small lactose functionalized G(2)-dendrimer 1 inhibited galectin-3-induced aggregation of the cancer cells. In contrast, dendrimer 4 (a larger, generation 6 dendrimer with 100 carbohydrate end groups) caused cancer cells to aggregate through a galectin-3 pathway. This study indicates that inhibition of cellular aggregation occurred because 1 provided competitive binding sites for galectin-3 (compared to its putative cancer cell ligand, TF-antigen on MUC1). Dendrimer 4, in contrast, provided an excess of ligands for galectin-3 binding; this caused crosslinking and aggregation of cells to be increased. PMID- 25138773 TI - Potential application of aqueous two-phase systems and three-phase partitioning for the recovery of superoxide dismutase from a clarified homogenate of Kluyveromyces marxianus. AB - Superoxide dismutase (SOD; EC 1.15.1.1) is an antioxidant enzyme that represents the primary cellular defense against superoxide radicals and has interesting applications in the medical and cosmetic industries. In the present work, the partition behavior of SOD in aqueous two-phase systems (ATPS) (using a standard solution and a complex extract from Kluyveromyces marxianus as sample) was characterized on different types of ATPS (polymer-polymer, polymer-salt, alcohol salt, and ionic liquid (IL)-salt). The systems composed of PEG 3350-potassium phosphate, 45% TLL, 0.5 M NaCl (315 U/mg, 87% recovery, and 15.1-fold purification) and t-butanol-20% ammonium sulfate (205.8 U/mg, 80% recovery and 9.8-fold purification), coupled with a subsequent 100 kDa ultrafiltration stage, allowed the design of a prototype process for the recovery and partial purification of the product of interest. The findings reported herein demonstrate the potential of PEG-salt ATPS for the potential recovery of SOD. PMID- 25138775 TI - A study of structure and properties of molecularly thin methanol film using the modified surface forces apparatus. AB - A novel approach for studying the adsorption and evaporation processes of molecularly thin methanol film by the modified surface forces apparatus (M-SFA) is reported. This method can be used precisely to measure the thickness, morphology, and mechanical properties of the film confined between two mica surfaces in a real-time manner at gas atmosphere. By observing the adsorption and evaporation processes of the methanol molecule, it is found that the first adsorbed layer of the methanol film on the mica surface behaves as a solid-like structure. The thickness of this layer is measured to be about 3.2 A, approximately equal to the diameter of a methanol molecule. Besides, this first adsorbed layer can carry normalized loads of more than 5.6 atm due to the carrying capacity conserved by the bond of mica-OH. The outer layers of the methanol film are further adsorbed with the increase of the exposure time, which are liquid-like and can be easily eliminated out from the substrate. The present study suggests that the interacting mode between hydroxy and mica is of great potential in material science and biomedical systems. PMID- 25138774 TI - TGR5: pathogenetic role and/or therapeutic target in fibrosing cholangitis? AB - Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease affecting the intrahepatic and extrahepatic biliary tree leading to bile duct strictures, progressive cholestasis, and development of liver fibrosis and cirrhosis. The pathogenesis of PSC is still elusive; however, both an immune-mediated injury of the bile ducts as well as increased recruitment of intestinal-primed T lymphocytes to the biliary tracts seem to contribute to disease development and progression. TGR5 (Gpbar-1) is a G-protein-coupled receptor responsive to bile acids, which is expressed in cholangiocytes, intestinal epithelial cells, and macrophages of the liver and intestine as well as in CD14-positive monocytes of the peripheral blood. Activation of TGR5 in biliary epithelial cells promotes chloride and bicarbonate secretion, triggers cell proliferation, and prevents apoptotic cell death. In immune cells, stimulation of TGR5 inhibits cytokine expression and secretion, thus reducing systemic as well as hepatic and intestinal inflammation. The expression pattern of TGR5 in the liver and intestine as well as the potential protective functions of TGR5 suggest a role for this receptor in the pathogenesis of PSC. While mutations in the coding region of the TGR5 gene are too rare to contribute to overall disease susceptibility, the expression and localization of the receptor have not been studied in PSC livers. Pharmacological activation of TGR5 in mice promotes protective mechanisms in biliary epithelial cells and reduces hepatic and systemic inflammation; however, it also provokes pruritus. Further studies are needed to predict the potential benefits as well as side effects of TGR5 agonist treatment in PSC patients. PMID- 25138776 TI - Shifting focus of medical physics education during residency training. PMID- 25138777 TI - Biological monitoring of particulate matter accumulated in the lungs of urban asthmatic children in the Tel-Aviv area. AB - PURPOSE: Lung inflammation from exposure to airborne particulate matter (PM) may be responsible for morbidity in asthma, but several studies using environmental monitoring data showed inconsistent results. Thus, the aim of this study was to evaluate the capability of induced sputum (IS) technology in order to biologically monitor PM in the lungs of urban asthmatic children. METHODS: We collected clinical, demographic, biological and environmental monitoring data on 136 children referred for asthma evaluations. The study participants were divided into two groups according to IS eosinophil counts of <3% (non-eosinophilic inflammation, n = 52) and >=3% (eosinophilic inflammation, n = 84). RESULTS: The eosinophilic group displays significantly higher levels of fractional exhaled nitric oxide than the non-eosinophilic one (58.8 +/- 47.5 vs 28.9 +/- 34.2 ppm, p = 0.007). Particles (0-2.5 and 0-5 um) comprised a strong risk factor for eosinophilic inflammation in IS (>=3%). Children with >80% of particles (0-2.5 um) out of the total PM accumulated in the airways displayed the highest OR 10.7 (CI 2.052-56.4 p = 0.005) for an existing eosinophilic inflammation. Heme oxygenase-1 (HO-1) enzyme levels in IS positively correlated with % eosinophils and with particles in IS ranging between 2 and 3 MUm. The level of HO-1 enzyme activity and FEV1/FVC in children with <3% eosinophils, but not >=3%, was positively and significantly correlated, showing a protective effect of HO-1. CONCLUSION: Accumulation of PM involves oxidative stress pathways and is a risk factor for developing eosinophilic inflammation in asthmatic children. IS can biologically monitor this process. PMID- 25138778 TI - Preoperative C-reactive protein in the serum: a prognostic biomarker for upper urinary tract urothelial carcinoma treated with radical nephroureterectomy. AB - OBJECTIVE: To investigate the impact of preoperative serum C-reactive protein (CRP) on clinicopathological features and prognosis in patients with upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU). PATIENTS AND METHODS: Data of 265 patients from three German centers who underwent RNU for UTUC without neoadjuvant chemotherapy between 1990 and 2012 were evaluated. Mean follow-up was 37 months (interquartile range 9-48). CRP was analyzed as a categorical and continuous variable for the prediction of recurrence-free survival (RFS), disease-specific survival (DSS) and all-cause survival (ACS) using uni- and multivariate Cox regression analyses. RESULTS: The optimal cutoff for CRP was calculated by the Youden index at 0.90 mg/dl. Elevated CRP was significantly associated with pT3/4 and pN+ in a preoperative model including age, gender, tumor multifocality, tumor localization and the Eastern Cooperative Oncology Group Performance Status. In a multivariable Cox regression model adjusted for features significant in univariable analysis, categorized and continuous CRP levels were both independent predictors for RFS [hazard ratio (HR) 1.18, p = 0.050; HR 1.03, p = 0.012] and DSS (HR 1.61, p = 0.026; HR 1.06, p = 0.001). Continuous CRP was an independent predictor for ACS (HR 1.05, p = 0.036). CONCLUSIONS: Elevated preoperative CRP is significantly associated with aggressive tumor biology and an independent predictor for poor survival after RNU. Preoperative serum CRP represents an easily obtainable and cost-effective marker in UTUC and may help in counseling patients with regard to operative management and/or adjuvant or neoadjuvant therapies. PMID- 25138780 TI - Progress towards bioorthogonal catalysis with organometallic compounds. AB - The catalysis of bioorthogonal transformations inside living organisms is a formidable challenge--yet bears great potential for future applications in chemical biology and medicinal chemistry. We herein disclose highly active organometallic ruthenium complexes for bioorthogonal catalysis under biologically relevant conditions and inside living cells. The catalysts uncage allyl carbamate protected amines with unprecedented high turnover numbers of up to 270 cycles in the presence of water, air, and millimolar concentrations of thiols. By live-cell imaging of HeLa cells and with the aid of a caged fluorescent probe we could reveal a rapid development of intense fluorescence within the cellular cytoplasm and therefore support the proposed bioorthogonality of the catalysts. In addition, to illustrate the manifold applications of bioorthogonal catalysis, we developed a method for catalytic in-cell activation of a caged anticancer drug, which efficiently induced apoptosis in HeLa cells. PMID- 25138781 TI - Solitary red-purple plaque on the chest of a 7-year-old boy: a quiz. Microvenular haemangioma. PMID- 25138782 TI - Governance practices and performance in US academic medical centers. AB - Recognition of the complex nature of modern health care delivery has led to interest in investigating the ways in which various factors, including governance structures and practices, influence health care quality. In this study, the chief executive officers (CEOs) of US academic medical centers were surveyed to elicit their perceptions of board structures, activities, and attitudes reflecting 6 widely identified governance best practices; the relationship between use of these practices and organizational performance, based on the University HealthSystem Consortium's Quality & Accountability rankings, was assessed. High performing hospitals showed greater use of all 6 practices, but the strongest evidence supported a focus on board member education and development, the rigorous use of performance measures to guide quality improvement, and systematic board self-assessment processes. All hospitals, even those with the highest quality ratings, had major gaps in their use of best practices for CEO and board assessments. These findings can serve as the basis for developing sound board improvement plans. PMID- 25138783 TI - Impact of a pharmacy education program on chronic kidney disease patients with complications in an outpatient clinic at police general hospital. PMID- 25138779 TI - Genome-wide association study of maternal and inherited effects on left-sided cardiac malformations. AB - Congenital left-sided lesions (LSLs) are serious, heritable malformations of the heart. However, little is known about the genetic causes of LSLs. This study was undertaken to identify common variants acting through the genotype of the affected individual (i.e. case) or the mother (e.g. via an in utero effect) that influence the risk of LSLs. A genome-wide association study (GWAS) was performed using data from 377 LSL case-parent triads, with follow-up studies in an independent sample of 224 triads and analysis of the combined data. Associations with both the case and maternal genotypes were assessed using log-linear analyses under an additive model. An association between LSLs and the case genotype for one intergenic SNP on chromosome 16 achieved genome-wide significance in the combined data (rs8061121, combined P = 4.0 * 10(-9); relative risk to heterozygote: 2.6, 95% CI: 1.9-3.7). In the combined data, there was also suggestive evidence of association between LSLs and the case genotype for a variant in the synaptoporin gene (rs1975649, combined P = 3.4 * 10(-7); relative risk to heterozygote: 1.6, 95% CI: 1.4-2.0) and between LSLs and the maternal genotype for an intergenic SNP on chromosome 10 (rs11008222, combined P = 6.3 * 10(-7); relative risk to heterozygote: 1.6, 95% CI: 1.4-2.0). This is the first GWAS of LSLs to evaluate associations with both the case and maternal genotypes. The results of this study identify three candidate LSL susceptibility loci, including one that appears to be associated with the risk of LSLs via the maternal genotype. PMID- 25138784 TI - Analgesic efficacy of prophylactic gabapentin and lornoxicam in preventing postendodontic pain. AB - OBJECTIVE: In dental applications, as in all other medical applications, pain needs to be prevented or at least controlled. The use of the tooth as a model for studying pain mechanisms is well established. In the current study, we aimed to evaluate and compare the analgesic effects of gabapentin and lornoxicam, respectively, vs a placebo for postendodontic treatment pain. DESIGN AND METHODS: Clinical research was planned as prospective, randomized, and placebo controlled. Each subject was given 600 mg gabapentin (group G: N = 30), 8 mg lornoxicam (group L: N = 30), or a placebo (group C: N = 30) 30 min prior to endodontic treatment. OUTCOME MEASURES: At 4 (T(3)), 8 (T(4)), 12 (T(5)), and 24 (T(6)) h after preoperative (T(0)) time points, the analgesic efficacies of the agents were evaluated by using the visual analog scale (VAS). RESULTS: In group G, VAS values were significantly greater at T(0) time point than at T(5) or T(6). T(0) time point VAS value in group L was lower than at T4 time point and greater than at T(6). In group C, T(0) time point VAS values were significantly lower at T(3) and T(5) time points and greater than at T(6) time point. VAS values in group G at T(5) time point were significantly lower than in group C or group L (P < 0.05). CONCLUSIONS: Based on the obtained data, prophylactic lornoxicam controlled postendodontic treatment pain more effectively than did the placebo drugs, and gabapentin was more effective in controlling the pain than either lornoxicam or the placebo. PMID- 25138786 TI - Increased serum levels of interleukin-18, -23 and -17 in Chinese patients with Alzheimer's disease. AB - AIMS: To evaluate the serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with Alzheimer's disease (AD), and explore correlations between the three cytokines and relevant parameters. METHODS: Serum concentrations of IL 18, IL-23 and IL-17 were measured by ELISA for 53 AD patients and 53 sex- and age matched healthy controls in a community of elderly individuals in a Shanghai suburb. RESULTS: Serum concentrations of IL-18, IL-23 and IL-17 were significantly higher in AD patients than controls. The serum level of IL-23 was observed to be significantly higher (p = 0.049) in female AD patients than male AD patients. In addition, a significantly inverse correlation was found between IL-18 and MMSE score (rs = -0.356, p = 0.011) for all AD patients. CONCLUSION: Elevated IL-18, IL-23 and IL-17 levels are observed in AD patients and differences may exist between males and females. Besides, IL-18 may correlate with the severity of AD. PMID- 25138785 TI - Relationship among 25-hydroxyvitamin D concentrations, insulin action, and cardiovascular disease risk in patients with essential hypertension. AB - BACKGROUND: Although low plasma 25-hydroxyvitamin D (25(OH)D) concentrations have been shown to predict risk of hypertension and associated cardiovascular disease (CVD), vitamin D repletion has not consistently lowered blood pressure or decreased CVD. One possibility for this discrepancy is the presence of considerable metabolic heterogeneity in patients with hypertension. To evaluate this possibility, we quantified relationships among insulin resistance, 25(OH)D concentration, and CVD risk factor profile in patients with essential hypertension. METHODS: Measurements were made of 25(OH)D concentrations, multiple CVD risk factors, and insulin resistance by the steady-state plasma glucose concentration during the insulin suppression test in 140 otherwise healthy patients with essential hypertension. RESULTS: As a group, the patients were overweight/obese and insulin resistant and had low 25(OH)D concentrations. The more insulin resistant the patients were, the worse the CVD risk profile was. In addition, the most insulin-resistant quartile had significantly lower 25(OH)D concentrations than the most insulin-sensitive quartile (20.3+/-1.4 vs. 25.8+/ 1.4ng/ml; P = 0.005). In the entire group, 25(OH)D concentration significantly correlated with magnitude of insulin resistance (steady-state plasma glucose concentration; r = -0.20; P = 0.02). CONCLUSIONS: There was considerable metabolic heterogeneity and substantial difference in magnitude of conventional CVD risk factors in patients with similar degrees of blood pressure elevation. The most insulin-resistant quartile of subjects had the lowest 25(OH)D concentration and the most adverse CVD risk profile, and they may be the subset of patients with essential hypertension most likely to benefit from vitamin D repletion. PMID- 25138787 TI - Usefulness of transient elastography by FibroScan for the evaluation of liver fibrosis. AB - INTRODUCTION: Liver stiffness measurement (LSM) is used for the assessment of liver fibrosis. However, there is limited data in Indian patients. AIMS AND OBJECTIVE: The aim of this study was to find the correlation of LSM, aspartate transaminase to platelet ratio index (APRI) with fibrosis as assessed by liver biopsy (LB), and predictors of discordance between LB and LSM. METHODS: One hundred and eighty-five consecutive patients who underwent liver biopsy and transient elastography (TE) were enrolled. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) was used to evaluate the accuracy of transient elastography and APRI in diagnosing significant fibrosis (F>2) and cirrhosis (F4). RESULTS: Predominant etiologies were hepatitis B (46 %) and hepatitis C (26 %). LSM was unsuccessful in ten patients (5 %) because of small intercostal space (n = 3) and obesity (n = 7). Fibrosis is significantly correlated with LSM (r = 0.901, p = 0.001) and APRI (r = 0.736, p = 0.001). There was a significant difference in median LSM value in patients with no fibrosis (F0) in comparison to patients having mild fibrosis [mild portal fibrosis (F1) + fibrosis with few septa (F2)] (4.5 vs. 7.5 kPa, p = 0.001) and advanced fibrosis [bridging fibrosis that is spreading and connecting to other areas that contain fibrosis (F3) + cirrhosis or advanced scarring of the liver (F4)] (4.5 vs. 19.4 kPa, p = 0.001). Similarly, there was a significant difference in mean APRI value in patients with F0 in comparison to patients having mild fibrosis (F1 + F2) (0.55 +/- 0.31 vs. 1.09 +/- 0.81, p = 0.001) and advanced fibrosis (F3 + F4) (2.3 +/- 1.3, p = 0.001). AUROC for diagnosis of significant fibrosis was 0.98 (95 % confidence interval (CI) 0.963-0.999) for TE and 0.865 (95 % CI 0.810-0.920) for APRI. Optimal TE value was 10.0 kPa for diagnosis of significant fibrosis and 14.7 kPa for cirrhosis with specificity and sensitivity of 89 %, 98 % and 96 %, and 97 %, respectively. On multivariate analysis, total bilirubin and histological activity index (HAI) were identified as an independent predictor of TE inaccuracy. CONCLUSION: LSM is a reliable predictor of hepatic fibrosis in Indian patients. LSM is superior to APRI for noninvasive diagnosis of hepatic fibrosis and cirrhosis, and high bilirubin (10.5 mg/dL) and Ishak HAI grade (>11) were independent predictors of discordance between LB and LSM. PMID- 25138789 TI - Regulation of angiopoietin-like protein 4 production during and after exercise. AB - Angiopoietin-like protein 4 (ANGPTL4) may regulate lipoprotein lipase-dependent plasma clearance of triacylglycerol from skeletal muscle during exercise. The aim of this study was to examine the importance of muscle in regulating ANGPTL4 in response to exercise. We sampled muscle biopsies and serum before, immediately after, and 2 h after 45 min of ergometer cycling. Sampling was done before and after a 12-week training intervention in controls and dysglycemic subjects. Moreover, fat biopsies were taken before and after the training intervention. The regulation of ANGPTL4 was also investigated in several tissues of exercising mice, and in cultured myotubes. ANGPTL4 levels in serum and expression in muscle were highest 2 h after exercise in both groups. Whereas ANGPTL4 was higher in muscle of exercising controls as compared to dysglycemic subjects, the opposite was observed in serum. In exercising mice, Angptl4 mRNA showed both higher basal expression and induction in liver compared to muscle. Angptl4 mRNA was much higher in adipose tissue than muscle and was also induced by exercise. We observed two mRNA isoforms of ANGPTL4 in muscle and fat in humans. Both were induced by exercise in muscle; one isoform was expressed 5- to 10-fold higher than the other. Studies in mice and cultured myotubes showed that both fatty acids and cortisol have the potential to increase ANGPTL4 expression in muscle during exercise. In conclusion, ANGPTL4 is markedly induced in muscle in response to exercise. However, liver and adipose tissue may contribute more than muscle to the exercise-induced increase in circulating ANGPTL4. PMID- 25138788 TI - Antibiotic use in acute pancreatitis: an Indian multicenter observational study. AB - INTRODUCTION: Prophylactic antibiotics are used frequently for acute pancreatitis (AP). Consensus guidelines do not recommend this currently, based on moderate quality evidence. In this study, we aimed to evaluate the antibiotic use pattern in AP in India and propose a risk-directed approach to antibiotic use in AP. MATERIAL AND METHODS: This multicenter study was conducted from 1 May 2013 to 31 July 2013. Eleven participants from eight tertiary centers completed a questionnaire that captured patient demographics, etiology, admission status, presence of (peri)pancreatic necrosis, severity of pancreatitis, details of antibiotic use, and clinical outcomes (total hospital stay, persistent organ failure, need for ICU, total days in ICU, development of infections, in-hospital mortality). RESULTS: A total of 200 proformas were analyzed. Seventy-three (36.5 %) had acute necrotizing pancreatitis (ANP). Eighty-nine (44.5 %), 52 (26 %), and 55 (27.5 %) patients had mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP), respectively. Forty-five (22.5 %) patients developed infections (unifocal 29; multifocal 16). One hundred thirty-four (67 %) patients received antibiotics, of which 89 (66.4 %) received prophylactic, while 45 (33.6 %) received therapeutic antibiotics. The distribution of antibiotic use according to the severity of AP was 43 (48.3 %) in patients with MAP (prophylactic in 41; therapeutic in 2), 36 (69.2 %) in patients with MSAP (prophylactic in 29; therapeutic in 7), and 55 (100 %) in patients with SAP (prophylactic in 19; therapeutic in 36). Therapeutic antibiotics were prescribed based on culture and sensitivity in 21 (46.7 %) patients. CONCLUSIONS: Despite nonrecommendation, prophylactic antibiotics are used frequently in AP. We emphasize on the need for multicenter randomized controlled trials on prophylactic antibiotics for AP based on a risk-directed approach, rather than a "blanket approach." PMID- 25138790 TI - Identification of the pre-Botzinger complex inspiratory center in calibrated "sandwich" slices from newborn mice with fluorescent Dbx1 interneurons. AB - Inspiratory active pre-Botzinger complex (preBotC) networks produce the neural rhythm that initiates and controls breathing movements. We previously identified the preBotC in the newborn rat brainstem and established anatomically defined transverse slices in which the preBotC remains active when exposed at one surface. This follow-up study uses a neonatal mouse model in which the preBotC as well as a genetically defined class of respiratory interneurons can be identified and selectively targeted for physiological recordings. The population of glutamatergic interneurons whose precursors express the transcription factor Dbx1 putatively comprises the core respiratory rhythmogenic circuit. Here, we used intersectional mouse genetics to identify the brainstem distribution of Dbx1 derived neurons in the context of observable respiratory marker structures. This reference brainstem atlas enabled online histology for generating calibrated sandwich slices to identify the preBotC location, which was heretofore unspecified for perinatal mice. Sensitivity to opioids ensured that slice rhythms originated from preBotC neurons and not parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN) cells because opioids depress preBotC, but not pFRG/RTN rhythms. We found that the preBotC is centered ~0.4 mm caudal to the facial motor nucleus in this Cre/lox reporter mouse during postnatal days 0 4. Our findings provide the essential basis for future optically guided electrophysiological and fluorescence imaging-based studies, as well as the application of other Cre-dependent tools to record or manipulate respiratory rhythmogenic neurons. These resources will ultimately help elucidate the mechanisms that promote respiratory-related oscillations of preBotC Dbx1-derived neurons and thus breathing. PMID- 25138793 TI - Erratum. PMID- 25138791 TI - The exocyst and regulatory GTPases in urinary exosomes. AB - Cilia, organelles that function as cellular antennae, are central to the pathogenesis of "ciliopathies", including various forms of polycystic kidney disease (PKD). To date, however, the molecular mechanisms controlling ciliogenesis and ciliary function remain incompletely understood. A recently proposed model of cell-cell communication, called "urocrine signaling", hypothesizes that a subset of membrane bound vesicles that are secreted into the urinary stream (termed exosome-like vesicles, or ELVs), carry cilia-specific proteins as cargo, interact with primary cilia, and affect downstream cellular functions. This study was undertaken to determine the role of the exocyst, a highly conserved eight-protein trafficking complex, in the secretion and/or retrieval of ELVs. We used Madin-Darby canine kidney (MDCK) cells expressing either Sec10-myc (a central component of the exocyst complex) or Smoothened-YFP (a ciliary protein found in ELVs) in experiments utilizing electron gold microscopy and live fluorescent microscopy, respectively. Additionally, human urinary exosomes were isolated via ultracentrifugation and subjected to mass spectrometry-based proteomics analysis to determine the composition of ELVs. We found, as determined by EM, that the exocyst localizes to primary cilia, and is present in vesicles attached to the cilium. Furthermore, the entire exocyst complex, as well as most of its known regulatory GTPases, are present in human urinary ELVs. Finally, in living MDCK cells, ELVs appear to interact with primary cilia using spinning disc confocal microscopy. These data suggest that the exocyst complex, in addition to its role in ciliogenesis, is centrally involved in the secretion and/or retrieval of urinary ELVs. PMID- 25138792 TI - Acute insulin resistance stimulates and insulin sensitization attenuates vascular smooth muscle cell migration and proliferation. AB - Differential activation/deactivation of insulin signaling, PI-3K and MAP-K pathways by high glucose and palmitate, with/out the insulin sensitizer pioglitazone (PIO), have been previously shown in vascular smooth muscle cells (VSMCs). To determine the biological impact of these molecular changes, we examined VSMC migration and proliferation ("M"&"P") patterns in similar conditions. VSMCs from healthy human coronary arteries were incubated in growth medium and "M"&"P" were analyzed after exposure to high glucose (25 mmol/L) +/- palmitate (200 MUmol/L) and +/- PIO (8 MUmol/L) for 5 h. "M"&"P" were assessed by: (1) polycarbonate membrane barrier with chemo-attractants and extended cell protrusions quantified by optical density (OD595 nm); (2) % change in radius area (2D Assay) using inverted microscopy images; and (3) cell viability assay expressed as cell absorbance (ABS) in media. "M" in 25 mmol/L glucose media increased by ~25% from baseline and % change in radius area rose from ~20% to ~30%. The addition of PIO was accompanied by a significant decrease in "M" from 0.25 +/- 0.02 to 0.19 +/- 0.02; a comparable decline from 0.25 +/- 0.02 to 0.18 +/- 0.02 was also seen with 25 mmol/L of glucose +200 MUmol/L of palmitate. When PIO was coincubated with high glucose plus palmitate there was a 50% reduction in % change in radius. A ~10% increase in ABS, reflecting augmented "P" in media with 25 mmol/L glucose versus control was documented. The addition of PIO reduced ABS from 0.208 +/- 0.03 to 0.183 +/- 0.06. Both high glucose and palmitate showed ABS of ~0.140 +/- 0.02, which decreased with PIO to ~0.120 +/- 0.02, indicating "P" was reduced. CONCLUSION: These results confirm that high glucose and palmitate stimulate VSMCs migration and proliferation in vitro, which is attenuated by coincubation with the insulin sensitizer PIO. Although, we cannot ascertain whether these functional changes are coincident with the activation/deactivation of signal molecules, our findings are consistent with the theory that differential regulation of insulin signaling pathways in VSMCs in insulin-resistant states plays an important role in inflammation, arterial wall thickening, and plaque formation during development of atherosclerosis. PMID- 25138794 TI - Circuit-specific changes in D-serine-dependent activation of the N-methyl-D aspartate receptor in the aging hippocampus. AB - Age-related memory deficits have recently been associated with the impaired expression of D-serine-dependent synaptic plasticity in neuronal networks of the hippocampal CA1 area. However, whether such functional alterations are common to the entire hippocampus during aging remains unknown. Here, we found that D-serine was also required for the induction of N-methyl-D-aspartate receptor (NMDA-R) dependent long-term potentiation (LTP) at perforant path-granule cell synapses of the dentate gyrus. LTP as well as isolated NMDA-R synaptic potentials were impaired in slices from aged rats, but in contrast to the CA1, this defect was not reversed by exogenous D-serine. The lower activation of the glycine-binding site by the endogenous co-agonist does not therefore appear to be a critical mechanism underlying age-related deficits in NMDA-R activation in the dentate gyrus. Instead, our data highlight the role of changes in presynaptic inputs as illustrated by the weaker responsiveness of afferent glutamatergic fibers, as well as changes in postsynaptic NMDA-R density. Thus, our study indicates that although NMDA-R-dependent mechanisms driving synaptic plasticity are quite similar between hippocampal circuits, they show regional differences in their susceptibility to aging, which could hamper the development of effective therapeutic strategies aimed at reducing cognitive aging. PMID- 25138796 TI - Paraneoplastic neuropathy with positive anti-Hu. A case report. PMID- 25138795 TI - Empyema due to Aggregatibacter aphrophilus and Parvimonas micra coinfection. PMID- 25138797 TI - Intrathoracic schwannoma of the vagus nerve. PMID- 25138798 TI - Thrombotic microangiopathy associated with tacrolimus in lung transplantation. AB - Thrombotic microangiopathy (TMA) is a rare complication associated with the use of calcineurin inhibitors in lung transplantation, irrespective of the underlying disease of the graft recipient. It usually occurs in incomplete forms, complicating and delaying diagnosis until damage is already irreversible. It is unrelated to time from transplantation and often presents with concomitant infection, which tends to confound diagnosis. The cases discussed here have a common causative agent and all present with concomitant infection. Treatment recommendations have changed in recent years with the introduction of plasmapheresis or, more recently, the availability of the antibody eculizumab. Notwithstanding, the most cost-effective measure is withdrawal or switching of the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should be considered in the management of transplantation patients. PMID- 25138799 TI - Complementary home mechanical ventilation techniques. SEPAR Year 2014. AB - This is a review of the different complementary techniques that are useful for optimizing home mechanical ventilation (HMV). Airway clearance is very important in patients with HMV and many patients, particularly those with reduced peak cough flow, require airway clearance (manual or assisted) or assisted cough techniques (manual or mechanical) and suctioning procedures, in addition to ventilation. In the case of invasive HMV, good tracheostomy cannula management is essential for success. HMV patients may have sleep disturbances that must be taken into account. Sleep studies including complete polysomnography or respiratory polygraphy are helpful for identifying patient-ventilator asynchrony. Other techniques, such as bronchoscopy or nutritional support, may be required in patients on HMV, particularly if percutaneous gastrostomy is required. Information on treatment efficacy can be obtained from HMV monitoring, using methods such as pulse oximetry, capnography or the internal programs of the ventilators themselves. Finally, the importance of the patient's subjective perception is reviewed, as this may potentially affect the success of the HMV. PMID- 25138800 TI - Case-control study of anaemia among middle-aged and elderly women in three rural areas of China. AB - OBJECTIVES: To propose a feasible suggestion to reduce the high prevalence of anaemia in middle-aged and elderly women by investigating risk factors, particularly nutritional factors, and analysing the effect on anaemia in three different rural areas of China. DESIGN: A case-control study. SETTING: Three counties of China. PARTICIPANTS: Women aged 50-75 years in the three counties. MAIN OUTCOME MEASURES: Adjusted OR (95% CI) of anaemia associated with diet, lifestyle and blood biochemical indices. RESULTS: Compared with controls, women with anaemia had lower body mass index (22.1 (3.2) kg/m(2) vs 23.2 (3.5) kg/m(2); p<0.001), a higher experience of shortage of food (45.0% vs 36.5%; p<0.001), less soy food intake (0.5 (0.3, 26.7) g/day vs 5.6 (0.4, 27.8) g/day; p<0.048), lower serum iron (13.4 (5.4) MUmol/L vs 16.4 (5.7) MUmol/L; p<0.001), lower ferritin (109.6 (85.6) ng/mL vs 131.0 (92.0) ng/mL; p<0.001), lower transferrin saturation levels (22.5 (9.5)% vs 26.8 (9.6)%; p<0.001) and higher levels of free erythrocyte protoporphyrin (42.4 (21.2) MUg/dL vs 39.6 (17.8) MUg/dL; p<0.001). Anaemia was significantly associated with BMI(OR=0.90, 95% CI (0.87 to 0.92)), food shortage experience (OR=1.39, 95% CI (1.15 to 1.69)), total protein (OR=0.66, 95%CI (0.54 to 0.80)), Albumin (OR=0.72, 95%CI (0.59 to 0.87)) in univariate analysis. Multivariate analysis showed that body mass index, experience of food shortage, total protein and albumin were independently related to anaemia. CONCLUSIONS: Among middle-aged and elderly women in rural China, the nutrition status of anaemic cases is far below that of controls. Lower body mass index and a greater experience of food shortage are closely related to anaemia. Improving the blood protein status by consuming protein-sufficient foods such as soy food is a feasible approach for elderly anaemic women. Further research is needed on the effect of chronic inflammation and infectious disease on anaemia in elderly women in rural China. PMID- 25138802 TI - Third-wave cognitive therapy versus mentalisation-based treatment for major depressive disorder: a randomised clinical trial. AB - OBJECTIVE: To compare the benefits and harms of third-wave cognitive therapy versus mentalisation-based therapy in a small sample of depressed participants. SETTING: The trial was conducted at an outpatient psychiatric clinic for non psychotic patients in Roskilde, Denmark. PARTICIPANTS: 44 consecutive adult participants diagnosed with major depressive disorder. INTERVENTIONS: 18 weeks of third-wave cognitive therapy (n=22) versus 18 weeks of mentalisation-based treatment (n=22). OUTCOMES: The primary outcome was the Hamilton Rating Scale for Depression (HDRS) at end of treatment (18 weeks). Secondary outcomes were: remission (HDRS <8), Beck's Depression Inventory, Symptom Checklist 90 Revised and The WHO-Five Well-being Index 1999. RESULTS: The trial inclusion lasted for about 2 years as planned but only 44 out of the planned 84 participants were randomised. Two mentalisation-based participants were lost to follow-up. The unadjusted analysis showed that third-wave participants compared with mentalisation-based participants did not differ significantly regarding the 18 weeks HDRS score (12.9 vs 17.0; mean difference -4.14; 95% CI -8.30 to 0.03; p=0.051). In the analysis adjusted for baseline HDRS score, the difference was favouring third-wave cognitive therapy (p=0.039). At 18 weeks, five of the third wave participants (22.7%) were in remission versus none of the mentalisation based participants (p=0.049). We recorded no suicide attempts or suicides during the intervention period in any of the 44 participants. No significant differences were found between the two intervention groups on the remaining secondary outcomes. CONCLUSIONS: Third-wave cognitive therapy may be more effective than mentalisation-based therapy for depressive symptoms measured on the HDRS. However, more randomised clinical trials are needed to assess the effects of third-wave cognitive therapy and mentalisation-based treatment for depression. TRIAL REGISTRATION NUMBER: Registered with Clinical Trials government identifier: NCT01070134. PMID- 25138801 TI - Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus: a systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. AB - OBJECTIVE: To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. DESIGN: A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. DATA SOURCES: The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded and LILACS to January 2013. STUDY SELECTION: Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. DATA EXTRACTION: Two authors independently assessed studies for inclusion and extracted data. RESULTS: 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96; p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of retinopathy, ketoacidosis and retinal photocoagulation were not consistently statistically significant between random and fixed effects models. The risk of severe hypoglycaemia was significantly increased with intensive glycaemic targets (1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data needed to demonstrate a relative risk reduction of 10% were, in general, inadequate. CONCLUSIONS: There was no significant effect towards improved all cause mortality when targeting intensive glycaemic control compared with conventional glycaemic control. However, there may be beneficial effects of targeting intensive glycaemic control on the composite macrovascular outcome and on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the data for retinopathy and ketoacidosis were inconsistent. There was a severe lack of reporting on patient relevant outcomes, and all trials had poor bias control. PMID- 25138803 TI - Incentivised case finding for depression in patients with chronic heart disease and diabetes in primary care: an ethnographic study. AB - OBJECTIVE: To examine the process of case finding for depression in people with diabetes and coronary heart disease within the context of a pay-for-performance scheme. DESIGN: Ethnographic study drawing on observations of practice routines and consultations, debriefing interviews with staff and patients and review of patient records. SETTING: General practices in Leeds, UK. PARTICIPANTS: 12 purposively sampled practices with a total of 119 staff; 63 consultation observations and 57 patient interviews. MAIN OUTCOME MEASURE: Audio recorded consultations and interviews with patients and healthcare professionals along with observation field notes were thematically analysed. We assessed outcomes of case finding from patient records. RESULTS: Case finding exacerbated the discordance between patient and professional agendas, the latter already dominated by the tightly structured and time-limited nature of chronic illness reviews. Professional beliefs and abilities affected how case finding was undertaken; there was uncertainty about how to ask the questions, particularly among nursing staff. Professionals were often wary of opening an emotional 'can of worms'. Subsequently, patient responses potentially suggesting emotional problems could be prematurely shut down by professionals. Patients did not understand why they were asked questions about depression. This sometimes led to defensive or even defiant answers to case finding. Follow-up of patients highlighted inconsistent systems and lines of communication for dealing with positive results on case finding. CONCLUSIONS: Case finding does not fit naturally within consultations; both professional and patient reactions somewhat subverted the process recommended by national guidance. Quality improvement strategies will need to take account of our results in two ways. First, despite their apparent simplicity, the case finding questions are not consultation friendly and acceptable alternative ways to raise the issue of depression need to be supported. Second, case finding needs to operate within structured pathways which can be accommodated within available systems and resources. PMID- 25138804 TI - Overall, gender and social inequalities in suicide mortality in Iran, 2006-2010: a time trend province-level study. AB - OBJECTIVES: Suicide is a major global health problem imposing a considerable burden on populations in terms of disability-adjusted life years. There has been an increasing trend in fatal and attempted suicide in Iran over the past few decades. The aim of the current study was to assess overall, gender and social inequalities across Iran's provinces during 2006-2010. DESIGN: Ecological study. SETTING: The data on distribution of population at the provinces were obtained from the Statistical Centre of Iran. The data on the annual number of deaths caused by suicide in each province were gathered from the Iranian Forensic Medicine Organization. METHODS: Suicide mortality rate per 100,000 population was calculated. Human Development Index was used as the provinces' social rank. Gini coefficient, rate ratio and Kunst and Mackenbach relative index of inequality were used to assess overall, gender and social inequalities, respectively. Annual percentage change was calculated using Joinpoint regression. RESULTS: Suicide mortality has slightly increased in Iran during 2006-2010. There was a substantial and constant overall inequality across the country over the study period. Male-to-female rate ratio was 2.34 (95% CI 1.45 to 3.79) over the same period. There were social inequalities in suicide mortality in favour of people in better-off provinces. In addition, there was an increasing trend in these social disparities over time, although it was not statistically significant. CONCLUSIONS: We found substantial overall, gender and social disparities in the distribution of suicide mortality across the provinces in Iran. The findings showed that men in the provinces with low socioeconomic status are at higher risk of suicide mortality. Further analyses are needed to explain these disparities. PMID- 25138805 TI - Geographic scale matters in detecting the relationship between neighbourhood food environments and obesity risk: an analysis of driver license records in Salt Lake County, Utah. AB - OBJECTIVES: Empirical studies of the association between neighbourhood food environments and individual obesity risk have found mixed results. One possible cause of these mixed findings is the variation in neighbourhood geographic scale used. The purpose of this paper was to examine how various neighbourhood geographic scales affected the estimated relationship between food environments and obesity risk. DESIGN: Cross-sectional secondary data analysis. SETTING: Salt Lake County, Utah, USA. PARTICIPANTS: 403,305 Salt Lake County adults 25-64 in the Utah driver license database between 1995 and 2008. ANALYSIS: Utah driver license data were geo-linked to 2000 US Census data and Dun & Bradstreet business data. Food outlets were classified into the categories of large grocery stores, convenience stores, limited-service restaurants and full-service restaurants, and measured at four neighbourhood geographic scales: Census block group, Census tract, ZIP code and a 1 km buffer around the resident's house. These measures were regressed on individual obesity status using multilevel random intercept regressions. OUTCOME: Obesity. RESULTS: Food environment was important for obesity but the scale of the relevant neighbourhood differs for different type of outlets: large grocery stores were not significant at all four geographic scales, limited-service restaurants at the medium-to-large scale (Census tract or larger) and convenience stores and full-service restaurants at the smallest scale (Census tract or smaller). CONCLUSIONS: The choice of neighbourhood geographic scale can affect the estimated significance of the association between neighbourhood food environments and individual obesity risk. However, variations in geographic scale alone do not explain the mixed findings in the literature. If researchers are constrained to use one geographic scale with multiple categories of food outlets, using Census tract or 1 km buffer as the neighbourhood geographic unit is likely to allow researchers to detect most significant relationships. PMID- 25138806 TI - Multimorbidity in a marginalised, street-health Australian population: a retrospective cohort study. AB - OBJECTIVES: Demographic and presentation profile of patients using an innovative mobile outreach clinic compared with mainstream practice. DESIGN: Retrospective cohort study. SETTING: Primary care mobile street health clinic and mainstream practice in Western Australia. PARTICIPANTS: 2587 street health and 4583 mainstream patients. MAIN OUTCOME MEASURES: Prevalence and patterns of chronic diseases in anatomical domains across the entire age spectrum of patients and disease severity burden using Cumulative Illness Rating Scale (CIRS). RESULTS: Multimorbidity (2+ CIRS domains) prevalence was significantly higher in the street health cohort (46.3%, 1199/2587) than age-sex-adjusted mainstream estimate (43.1%, 2000/4583), p=0.011. Multimorbidity prevalence was significantly higher in street health patients <45 years (37.7%, 615/1649) compared with age-sex adjusted mainstream patients (33%, 977/2961), p=0.003 but significantly lower if 65+ years (62%, 114/184 vs 90.7%, 322/355, p<0.001). Controlling for age and gender, the mean CIRS Severity Index score for street health (M=1.4, SD=0.91) was significantly higher than for mainstream patients (M=1.1, SD=0.80), p<0.001. Furthermore, 44.2% (530/1199) of street health patients had at least one level 3 or 4 score across domains compared with 18.3% (420/2294) for mainstream patients, p<0.001. Street health population comprised 29.6% (766/2587) Aboriginal patients with 50.4% (386/766) having multimorbidity compared with 44.6% (813/1821) for non Aboriginals, p=0.007. There were no comprehensive data on Indigenous status in the mainstream cohort available for comparison. Musculoskeletal, respiratory and psychiatric domains were most commonly affected with multimorbidity significantly associated with male gender, increasing age and Indigenous status. CONCLUSIONS: Age-sex-adjusted multimorbidity prevalence and disease severity is higher in the street health cohort. Earlier onset (23-34 years) multimorbidity is found in the street health cohort but prevalence is lower in 65+ years than in mainstream patients. Multimorbidity prevalence is higher for Aboriginal patients of all ages. PMID- 25138808 TI - Analgesia dose prescribing and estimated glomerular filtration rate decline: a general practice database linkage cohort study. AB - OBJECTIVE: We aimed to quantify the short-term effect of non-steroidal anti inflammatory drugs (NSAIDs), aspirin and paracetamol analgesia dose prescribing on estimated glomerular filtration rate (eGFR) decline in the general practice population. DESIGN: A population-based longitudinal clinical data linkage cohort study. SETTING: Two large general practices in North Staffordshire, UK. PARTICIPANTS: Patients aged 40 years and over with >=2 eGFR measurements spaced >=90 days apart between 1 January 2009 and 31 December 2010 were selected. EXPOSURE: Using WHO Defined Daily Dose standardised cumulative analgesia prescribing, patients were categorised into non-user, normal and high-dose groups. OUTCOME MEASURE: The primary outcome was defined as a >5 mL/min/1.73 m(2)/year eGFR decrease between the first and last eGFR. Logistic regression analyses were used to estimate risk, adjusting for sociodemographics, comorbidity, baseline chronic kidney disease (CKD) status, renin-angiotensin system inhibitors and other analgesia prescribing. RESULTS: There were 4145 patients (mean age 66 years, 55% female) with an analgesia prescribing prevalence of 17.2% for NSAIDs, 39% for aspirin and 22% for paracetamol and stage 3-5 CKD prevalence was 16.1% (n=667). Normal or high-dose NSAID and paracetamol prescribing was not significantly associated with eGFR decline. High-dose aspirin prescribing was associated with a reduced risk of eGFR decline in patients with a baseline (first) eGFR >=60 mL/min/1.73 m(2); OR=0.52 (95% CI 0.35 to 0.77). CONCLUSIONS: NSAID, aspirin and paracetamol prescribing over 2 years did not significantly affect eGFR decline with a reduced risk of eGFR decline in high dose aspirin users with well-preserved renal function. However, the long-term effects of analgesia use on eGFR decline remain to be determined. PMID- 25138809 TI - Evaluation of My Medication Passport: a patient-completed aide-memoire designed by patients, for patients, to help towards medicines optimisation. AB - OBJECTIVES: A passport-sized booklet, designed by patients for patients to record details about their medicines, has been developed as part of a wider project focusing on improving prescribing in the elderly ('ImPE'). We undertook an evaluation of 'My Medication Passport' to gain an understanding of its value to patients and how it may be used in communications about medicines. SETTING: The Passport was launched in secondary care with the initial users being older people discharged home after an admission to one of the four North West London participating Trusts. The uptake subsequently spread to other (community) locations and other age groups. PARTICIPANTS: We recruited more than 200 patients from a cohort who had been given a passport as part of the improvement projects at one of four sites. Of them, 63% (133) completed the structured telephone questionnaire including 27% for whom English was not their first language. Approximately half of the respondents were male and 40% were over 70 years of age. RESULTS: More than half of the respondents had found their medication passport useful or helpful in some way; 42% through sharing details from it with others (most frequently family, carer or doctor) or using it as a platform for conversations with healthcare professionals. One-third of those questioned carried the passport with them at all times. CONCLUSIONS: My Medication Passport has been positively evaluated; we have a better understanding of how it is used by patients, what they are recording and how it can be an aid to dialogue about medicines with family, carers and healthcare professionals. Further development and spread is underway including an App for smartphones that will be subject to wider evaluation to include feedback from clinicians. PMID- 25138807 TI - MAXimising Involvement in MUltiMorbidity (MAXIMUM) in primary care: protocol for an observation and interview study of patients, GPs and other care providers to identify ways of reducing patient safety failures. AB - INTRODUCTION: Increasing numbers of older people are living with multiple long term health conditions but global healthcare systems and clinical guidelines have traditionally focused on the management of single conditions. Having two or more long-term conditions, or 'multimorbidity', is associated with a range of adverse consequences and poor outcomes and could put patients at increased risk of safety failures. Traditionally, most research into patient safety failures has explored hospital or inpatient settings. Much less is known about patient safety failures in primary care. Our core aims are to understand the mechanisms by which multimorbidity leads to safety failures, to explore the different ways in which patients and services respond (or fail to respond), and to identify opportunities for intervention. METHODS AND ANALYSIS: We plan to undertake an applied ethnographic study of patients with multimorbidity. Patients' interactions and environments, relevant to their healthcare, will be studied through observations, diary methods and semistructured interviews. A framework, based on previous studies, will be used to organise the collection and analysis of field notes, observations and other qualitative data. This framework includes the domains: access breakdowns, communication breakdowns, continuity of care errors, relationship breakdowns and technical errors. ETHICS AND DISSEMINATION: Ethical approval was received from the National Health Service Research Ethics Committee for Wales. An individual case study approach is likely to be most fruitful for exploring the mechanisms by which multimorbidity leads to safety failures. A longitudinal and multiperspective approach will allow for the constant comparison of patient, carer and healthcare worker expectations and experiences related to the provision, integration and management of complex care. This data will be used to explore ways of engaging patients and carers more in their own care using shared decision-making, patient empowerment or other relevant models. PMID- 25138810 TI - Relationship between socioeconomic status and type 2 diabetes: results from Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012. AB - OBJECTIVE: To examine the relationship between socioeconomic status (SES) and type 2 diabetes using the Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012. DESIGN: A pooled sample cross-sectional study. SETTING: A nationally representative population survey data. PARTICIPANTS: A total of 14,330 individuals who participated in the KNHANES 2010-2012 were included in our analysis. PRIMARY OUTCOME: Prevalence of type 2 diabetes. RESULTS: The relationship between SES and type 2 diabetes was assessed using logistic regression after adjusting for covariates including age, gender, marital status, region, body mass index, physical activity, smoking and high-risk drinking behaviour. After adjustment for covariates, our results indicated that individuals with the lowest income were more likely to have type 2 diabetes than those with the highest income (OR 1.35; 95% CI 1.08 to 1.72). In addition, lower educational attainment was an independent factor for a higher prevalence of type 2 diabetes in Korea. CONCLUSIONS: These findings suggest the need for developing a health policy to ameliorate socioeconomic inequalities, in particular income and education-related disparities in type 2 diabetes, along with risk factors at the individual level. In addition, future investigations of type 2 diabetes among Koreans should pay more attention to the social determinants of diabetes in order to understand the various causes of the condition. PMID- 25138811 TI - Decision aids for randomised controlled trials: a qualitative exploration of stakeholders' views. AB - OBJECTIVES: To explore stakeholders' perceptions of decision aids designed to support the informed consent decision-making process for randomised controlled trials. DESIGN: Qualitative semistructured interviews. Participants were provided with prototype trial decision aids in advance to stimulate discussion. Interviews were analysed using an established interpretive approach. PARTICIPANTS: 23 stakeholders: Trial Managers (n=5); Research Nurses (n=5); Ethics Committee Chairs (n=5); patients (n=4) and Clinical Principal Investigators (n=4). SETTING: Embedded within two ongoing randomised controlled trials. All interviews conducted with UK-based participants. RESULTS: Certain key aspects (eg, values clarification exercises, presentation of probabilities, experiences of others and balance of options) in the prototype decision aids were perceived by all stakeholders as having a significant advantage (over existing patient information leaflets) in terms of supporting well informed appropriate decisions. However, there were some important differences between the stakeholder groups on specific content (eg, language used in the section on positive and negative features of taking part in a trial and the overall length of the trial decision aids). Generally the stakeholders believed trial decision aids have the potential to better engage potential participants in the decision-making process and allow them to make more personally relevant decisions about their participation. CONCLUSIONS: Compared to existing patient information leaflets, stakeholders perceived decision aids for trial participation to have the potential to promote a more 'informed' decision-making process. Further efforts to develop, refine and formally evaluate trial decision aids should be explored. PMID- 25138812 TI - Comparison and validation of International Consensus Diagnostic Criteria for diagnosis of autoimmune pancreatitis from pancreatic cancer in a Taiwanese cohort. AB - OBJECTIVES: The International Consensus Diagnostic Criteria (ICDC) designed to diagnosis autoimmune pancreatitis (AIP) has been proposed recently. The diagnostic performance of ICDC has not been previously evaluated in diffuse-type and focal-type AIP, respectively, in comparison with the revised HISORt and Asian criteria in Taiwan. DESIGN: Prospective, consecutive patient cohort. SETTING: Largest tertiary referred centre hospital managing pancreatic disease in Taiwan. PARTICIPANTS: 188 patients with AIP and 130 with tissue proofed pancreatic adenocarcinoma were consecutively recruited. INTERVENTIONS: The ICDC, as well as revised HISORt and Asian criteria, was applied for each participant. Each diagnostic criterion of ICDC was validated with special reference to levels 1 and 2 in diffuse-type and focal-type AIP. OUTCOMES: Sensitivity, specificity and accuracy. Each diagnostic criterion of ICDC was validated with special reference to levels 1 and 2 in AIP and focal-type AIP. RESULTS: The sensitivity, specificity and accuracy of ICDC for all AIP were the best: 89.4%, 100% and 93.7%, respectively, in these three criteria. The sensitivity, specificity and accuracy of ICDC for focal-type AIP (84.9%, 100% and 93.8%) were also the best among these three criteria. The area under the curve of receiver-operator characteristic of ICDC was 0.95 (95% CI 0.92 to 0.97) in all AIP and 0.93 (95% CI 0.88 to 0.97) in focal-type AIP. CONCLUSIONS: The sensitivity, specificity and accuracy of ICDC are higher than the revised HISORt and Asian criteria. The sensitivity, specificity and accuracy of each criterion are higher in diffuse type AIP compared with focal-type AIP. Under the same specificity, the sensitivity and accuracy of ICDC are higher than other diagnostic criteria in focal-type AIP. ICDC has better diagnostic performance compared with previously proposed diagnostic criteria in diffuse-type and focal-type AIP. PMID- 25138813 TI - A community-based survey for different abnormal glucose metabolism among pregnant women in a random household study (SAUDI-DM). AB - OBJECTIVE: To assess the prevalence and risk factors of gestational diabetes mellitus (GDM) in a population known to have a high prevalence of abnormal glucose metabolism. METHODS: A household random population-based cross-sectional study of 13,627 women in the childbearing age, who were subjected to fasting plasma glucose if they were not known to have been diagnosed before with any type of diabetes. GDM cases were diagnosed using the International Association of Diabetes and Pregnancy Study Group (IAPSG) criteria. RESULTS: The overall GDM prevalence was 36.6%, categorised into 32.4% new cases and 4.2% known cases. Another 3.6% had preconception type 1 or 2 diabetes. GDM cases were older and had a significantly higher body mass index, in addition to a higher rate of macrocosmic baby and history of GDM. Monthly income, educational level, living in urban areas and smoking were not found to be significantly different between normal and GDM cases. The most important and significant risk factors for GDM were history of GDM, macrosomic baby, obesity and age >30 years. However, hypertension, low high-density lipoprotein, family history of diabetes and increased triglycerides did not show any significant effect on GDM prevalence in this cohort. CONCLUSIONS: This society is facing a real burden of abnormal glucose metabolism during pregnancy, where almost half of the pregnant women are subjected to maternal and neonatal complications. Early screening of pregnant women, especially those at a high risk for GDM, is mandatory to identify and manage those cases. PMID- 25138814 TI - A study protocol for a randomised open-label clinical trial of artesunate mefloquine versus chloroquine in patients with non-severe Plasmodium knowlesi malaria in Sabah, Malaysia (ACT KNOW trial). AB - INTRODUCTION: Malaria due to Plasmodium knowlesi is reported throughout South East Asia, and is the commonest cause of it in Malaysia. P. knowlesi replicates every 24 h and can cause severe disease and death. Current 2010 WHO Malaria Treatment Guidelines have no recommendations for the optimal treatment of non severe knowlesi malaria. Artemisinin-combination therapies (ACT) and chloroquine have each been successfully used to treat knowlesi malaria; however, the rapidity of parasite clearance has not been prospectively compared. Malaysia's national policy for malaria pre-elimination involves mandatory hospital admission for confirmed malaria cases with discharge only after two negative blood films; use of a more rapidly acting antimalarial agent would have health cost benefits. P. knowlesi is commonly microscopically misreported as P. malariae, P. falciparum or P. vivax, with a high proportion of the latter two species being chloroquine resistant in Malaysia. A unified ACT-treatment protocol would provide effective blood stage malaria treatment for all Plasmodium species. METHODS AND ANALYSIS: ACT KNOW, the first randomised controlled trial ever performed in knowlesi malaria, is a two-arm open-label trial with enrolments over a 2-year period at three district sites in Sabah, powered to show a difference in proportion of patients negative for malaria by microscopy at 24 h between treatment arms (clinicaltrials.gov #NCT01708876). Enrolments started in December 2012, with completion expected by September 2014. A total sample size of 228 is required to give 90% power (alpha 0.05) to determine the primary end point using intention-to treat analysis. Secondary end points include parasite clearance time, rates of recurrent infection/treatment failure to day 42, gametocyte carriage throughout follow-up and rates of anaemia at day 28, as determined by survival analysis. ETHICS AND DISSEMINATION: This study has been approved by relevant institutional ethics committees in Malaysia and Australia. Results will be disseminated to inform knowlesi malaria treatment policy in this region through peer-reviewed publications and academic presentations. TRIAL REGISTRATION NUMBER: NCT01708876. PMID- 25138817 TI - Implementation and use of electronic synoptic cancer reporting: an explorative case study of six Norwegian pathology laboratories. AB - BACKGROUND: The information contained in histopathology reports on surgical resections of cancer is fundamental for both patient treatment and cancer registries. Electronic synoptic histopathology reporting is considered superior to traditional narrative reporting with respect to both completeness and feasibility of data use. An electronic template for colorectal cancer reporting was introduced in Norway in 2005, but implementation has varied greatly between different pathology departments. In 2012, four pathology departments and the Norwegian Cancer Registry started a new initiative on electronic cancer reporting. As part of this initiative, this study was undertaken to learn more about factors influencing implementation and use. METHODS: Qualitative and quantitative data were obtained from six of the 17 public pathology departments in Norway using explorative case study methodology. Methods included document studies, semi-structured interviews with key informants, and audits on actual template use. A systematic analysis of data was conducted based on theoretical models for project management, stakeholder engagement, and individual acceptance of new information technology. RESULTS: Most key informants had a positive view on synoptic reporting, and five departments had tested the electronic template. Of these, four had implemented the template while one department had decided not to implement it due to layout concerns. Of the four departments using the template in daily routine, one had compulsory use, two consensus based use, while the fourth had voluntary use. Annual average usage of the electronic template in the three departments with compulsory or consensus based use was 92% compared to 53% in the department with voluntary use. CONCLUSIONS: There was a general positive attitude towards electronic synoptic reporting. Reasons for not implementing the colorectal template were specific technical and quality issues not adequately addressed by the project organization having developed the template. A formal assessment of project outcomes with a task force handling such technical issues should accordingly have been established as part of the project. After an organizational decision on implementation, perceived job relevance and practical benefits are factors important for individual template use. Consistent high long-term usage was related to a departmental environment with a consensus based decision on use. PMID- 25138815 TI - Protocol for the RT Prepare Trial: a multiple-baseline study of radiation therapists delivering education and support to women with breast cancer who are referred for radiotherapy. AB - INTRODUCTION: There is limited evidence to guide the preparation of patients for radiotherapy. This paper describes the protocol for an evaluation of a radiation therapist led education intervention delivered to patients with breast cancer in order to reduce psychological distress. METHODS: A multiple-baseline study is being used. Usual care data is being collected prior to the start of the intervention at each of three sites. The intervention is delivered by radiation therapists consulting with patients prior to their treatment planning and on the first day of treatment. The intervention focuses on providing sensory and procedural information to patients and reducing pretreatment anxiety. Recruitment is occurring in three states in Australia. Eligible participants are patients who have been referred for radiotherapy to treat breast cancer. 200 patients will be recruited during a usual care phase and, thereafter, 200 patients in the intervention phase. Measures will be collected on four occasions-after meeting with their radiation oncologist, prior to treatment planning, on the first day of treatment and after treatment completion. The primary hypothesis is that patients who receive the radiotherapy preparatory intervention will report a significantly greater decrease in psychological distress from baseline to prior to radiotherapy treatment planning in comparison with the usual care group. Secondary outcome measures include concerns about radiotherapy, patient knowledge of radiotherapy, patient preparedness and quality of life. Patient health system usage and costs will also be measured. Multilevel mixed effects regression models will be applied to test for intervention effects. ETHICS: Ethics approval has been gained from Curtin University and the three recruiting sites. DISSEMINATION: Results will be reported in international peer reviewed journals. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registration: ACTRN12611001000998. PMID- 25138819 TI - Dissection of the posterior wall by guide-wire during internal jugular vein catheterization. AB - We report a case of posterior wall hematoma formation in the internal jugular vein after the puncture of central vein. An 82-year-old woman was scheduled for laparotomy for an abdominal incisional hernia. After induction of general anesthesia, we performed central venous catheterization via the right internal jugular vein under ultrasound guidance in the short-axis view and out-of plane technique. The ultrasound view after insertion of a guide-wire revealed a hematoma-like space on the posterior wall of the vein. We removed and reinserted the guide-wire. This time, insertion of the wire and catheter was uneventful. Seven days after the surgery, no hematoma-like space was found in the vein. The malposition of the guide-wire was detected before dilation, which enabled us to avoid complications in this case. We should note that the confirmation of guide wire placement in the vein is important during ultrasound-guided central venous catheterization. PMID- 25138816 TI - Structural analysis of diheme cytochrome c by hydrogen-deuterium exchange mass spectrometry and homology modeling. AB - A lack of X-ray or nuclear magnetic resonance structures of proteins inhibits their further study and characterization, motivating the development of new ways of analyzing structural information without crystal structures. The combination of hydrogen-deuterium exchange mass spectrometry (HDX-MS) data in conjunction with homology modeling can provide improved structure and mechanistic predictions. Here a unique diheme cytochrome c (DHCC) protein from Heliobacterium modesticaldum is studied with both HDX and homology modeling to bring some definition of the structure of the protein and its role. Specifically, HDX data were used to guide the homology modeling to yield a more functionally relevant structural model of DHCC. PMID- 25138818 TI - Skeletal versus conventional intraoral anchorage for the treatment of class II malocclusion: dentoalveolar and skeletal effects. AB - BACKGROUND: The purpose of this retrospective study is to investigate the dentoalveolar and skeletal effects of two distalizing protocols featuring different anchorage systems used in patients with class II malocclusion: the MGBM system (skeletal anchorage) and Pendulum (intraoral anchorage). METHODS: The sample comprised 57 patients who were assigned to one of the two treatments: the MGBM group (30 patients, mean age 13.3 +/- 2.3 years) or the Pendulum group (27 patients, mean age 12.8 +/- 1.7 years). Three serial cephalograms were obtained at baseline (T0), after molar distalization (T1), and after fixed appliance treatment (T2). Esthetic, skeletal, and dental parameters were considered. Pancherz's superimposition method was used to assess sagittal dental changes. The initial and final measurements and treatment changes were compared by means of a paired t test or a paired Wilcoxon test. Statistical significance was tested at p < 0.05, p < 0.01, and p < 0.001. RESULTS: In the MGBM group, the upper molar distalization was achieved in 7 months and showed a mean value of 4.9 mm (ms PLO); the amount of molar relationship correction was 5.9 mm. In the Pendulum group, the upper molar distalization was obtained in 9 months and showed a mean value of 2.5 mm (ms-PLO), while the molar relationship correction amounted to 4.9 mm. Anterior anchorage loss occurred in both groups, although in the MGBM group, there was less mesial movement of the premolars. CONCLUSIONS: The MGBM system and the Pendulum appliance are both effective in the correction of class II malocclusions. The MGBM system was found to be more efficient than the Pendulum appliance, producing greater molar distalization in a shorter treatment time. PMID- 25138821 TI - Anisocoria after anesthesia induction caused by Adie syndrome. PMID- 25138820 TI - An unusual case of post-anaesthesia voice loss. PMID- 25138822 TI - An assessment of the awareness of local anesthetic systemic toxicity among multi specialty postgraduate residents. AB - Local anesthetics (LAs) are extensively used in clinical practice by both anesthesiologists and non-anesthesiologists and are often associated with systemic toxicity. We hypothesize that this awareness is inadequate among medical specialists and entails a risk of misdiagnosis and underreporting of such events. We therefore conducted a cross-sectional questionnaire-based study to assess the level of understanding of LA use and effective management of systemic toxicity among 200 postgraduate residents of various specialties (with the exception of anesthesiology) in a tertiary care hospital in India from October to December 2013. Among those residents who had used LAs (193/200), 27 and 25 % of responders correctly identified the toxic doses of lidocaine and of lidocaine + adrenaline, respectively. Of the responders, 70 % always performed a negative aspiration of blood before injecting the drug, 27 % sometimes aspirated and the remaining 3 % never aspirated. The majority of the responders (93 %) were unaware of the toxic dose of bupivacaine. Only 70 % of responders believed that LAs could be toxic [95 % confidence interval (CI) 65.5-74.5 %], and 81 % of these correctly identified the signs and symptoms of cardiotoxicity. Only 2 % of responders knew that lipid emulsion is a part of its treatment (95 % CI 0.6-3.4 %). Based on these results, there is a definite need to increase the awareness of detection and treatment of local anesthetic toxicity among all medical practitioners who regularly use LAs. PMID- 25138823 TI - Anterior temporal atrophy and posterior progression in patients with Parkinson's disease. AB - BACKGROUND: Parkinson's disease (PD) is characterized by specific motor and nonmotor impairments. This suggests that PD is characterized by disease-specific regional cortical atrophy. Given the change of symptoms over time, a concurrent increase in regional atrophy may further be assumed to reflect the dynamic process of disease progression. METHODS: In this study we retrospectively collected T1-weighted MRI scans from previous studies performed in our center, enabling the comparison of gray matter atrophy in 77 PD patients with 87 controls using voxel-based morphometry (VBM). This large VBM analysis provided the opportunity to investigate cortical atrophy in relation with disease progression. RESULTS: We found significant PD-related reductions of gray matter density bilaterally in the anterior temporal cortex, the left inferior frontal and left extrastriate visual cortex, independent from normal aging. The anterior temporal cortex did not show major progression, whereas particularly the posterior parts of the lateral temporal cortex and adjacent extrastriate visual cortex occurred at a later stage of disease. CONCLUSIONS: Temporal pole atrophy as an early sign of PD is consistent with the PD pathology classification of Braak. The initial anterior temporal atrophy with spread to occipitotemporal and posterior parietal regions may subserve 'emotion-based' sensorimotor transformations and deficits in the visual domain, respectively, which may be regarded as premotor symptoms. PMID- 25138824 TI - Uterine fibroid research: a work in progress. PMID- 25138825 TI - Enodthelin 1 is elevated in plasma and explants from patients having uterine leiomyomas. AB - OBJECTIVE: To determine a role for endothelin (ET) in progression of uterine fibroids. DESIGN: An in vitro model of fibroid and myometrium cultivation. PATIENTS: A total of 32 women undergoing hysterectomies for uterine fibroids and 11 women undergoing hysterectomies for abnormal uterine bleeding (control population). RESULTS: Women with uterine fibroids were hypertensive and displayed significantly greater circulating ET-1 compared to control patients. Secretion of ET-1 was greater from the fibroids compared to myometrium explants. Endothelin 1 secretion was attenuated with blockade of the angiotensin II type 1 or endothelinA receptors. Hypoxia stimulated ET-1 secretion from both myometrium and fibroid explants. Preproendothelin messenger RNA expression increased with hypoxia from fibroid explants compared to normoxic controls. CONCLUSIONS: These data support the hypothesis that uterine fibroids are associated with hypertension and increased ET-1, which is exacerbated with hypoxia. These data suggest a possible link between mechanisms of blood pressure regulation and development of uterine leiomyoma. PMID- 25138826 TI - Management of hypertension and heart failure in patients with Addison's disease. AB - Addison's disease may be complicated by hypertension and less commonly by heart failure. We review the pathophysiology of the renin-angiotensin-aldosterone axis in Addison's disease and how this is altered in the setting of hypertension and heart failure. An essential first step in management in both conditions is optimizing glucocorticoid replacement and considering dose reduction if excessive. Following this, if a patient with Addison's disease remains hypertensive, the fludrocortisone dose should be reviewed and reduced if there are clinical and/or biochemical signs of mineralocorticoid excess. In the absence of such signs, where the renin is towards the upper end of the normal range or elevated, an angiotensin II (AII) receptor antagonist or angiotensin converting enzyme (ACE) inhibitor is the treatment of choice, and the fludrocortisone dose should remain unchanged. Dihydropyridine calcium channel blockers are clinically useful as second line agents, but diuretics should be avoided. In the setting of heart failure, there is an increase in total body sodium and water; therefore, it is appropriate to reduce and rarely consider ceasing the fludrocortisone. Loop diuretics may be used, but not aldosterone antagonists such as spironolactone or eplerenone. Standard treatment with ACE inhibitors, or as an alternative, AII receptor antagonists, are appropriate. Measurements of renin are no longer helpful in heart failure to determine the volume status but plasma levels of brain natriuretic peptide (BNP/proBNP) may help guide therapy. PMID- 25138827 TI - The importance of nanoparticle shape in cancer drug delivery. AB - INTRODUCTION: Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy. AREAS COVERED: This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and overall drug efficacy. By comparing spherical and nonspherical nanoparticles, they establish some general design principles to serve as guidelines for developing the next generation of nanocarriers for drug delivery. EXPERT OPINION: Pioneering studies on nanoparticles show that nonspherical shapes show great promise as cancer drug delivery vectors. Filamentous or worm-like micelles together with other rare morphologies such as needles or disks may become the norm for next-generation drug carriers, though at present, traditional spherical micelles remain the dominant shape of nanocarriers described in the literature due to synthesis and testing difficulties. The few reports that do exist describing nonspherical nanoparticles show a number of favorable properties that should encourage more efforts to develop facile and versatile nanoparticle synthesis methodologies with the flexibility to create different shapes, tunable sizes and adaptable surface chemistries. In addition, the authors note that there is a current lack of understanding into the factors governing (and optimizing) the inter-relationships of size, surface characteristics and shapes of many nanoparticles proposed for use in cancer therapy. PMID- 25138831 TI - We need to help nurses practise what they preach. AB - Are you heavier than you would like to be? Nurses would no doubt respond in much the same way as any other group of people, with many saying 'yes' in response. The question is whether healthcare professionals should feel obliged to set a good example by living healthy lifestyles. PMID- 25138830 TI - Editorial Comment to Positron emission tomography/magnetic resonance imaging with 68Gallium-labeled ligand of prostate-specific membrane antigen: promising novel option in prostate cancer imaging? PMID- 25138828 TI - Metal nanobullets for multidrug resistant bacteria and biofilms. AB - Infectious diseases were one of the major causes of mortality until now because drug-resistant bacteria have arisen under broad use and abuse of antibacterial drugs. These multidrug-resistant bacteria pose a major challenge to the effective control of bacterial infections and this threat has prompted the development of alternative strategies to treat bacterial diseases. Recently, use of metallic nanoparticles (NPs) as antibacterial agents is one of the promising strategies against bacterial drug resistance. This review first describes mechanisms of bacterial drug resistance and then focuses on the properties and applications of metallic NPs as antibiotic agents to deal with antibiotic-sensitive and resistant bacteria. We also provide an overview of metallic NPs as bactericidal agents combating antibiotic-resistant bacteria and their potential in vivo toxicology for further drug development. PMID- 25138833 TI - RCN head of policy says costs of nurse training pilot are prohibitive. AB - A quarter of the 250 prospective nursing students recruited to a national training pilot set up to give them up to a year's caring experience have not pursued nursing as a career, Nursing Standard has learned. PMID- 25138834 TI - NMC offers nurses instalment option on paying annual registration fees. AB - The Nursing and Midwifery Council (NMC) is asking nurses if they would like the option to pay their annual L100 registration fee in instalments. PMID- 25138835 TI - College lobbies to keep NHS out of EU-US trade deal. AB - The RCN will begin lobbying European Union politicians and officials in the autumn to exclude health services from a controversial free trade agreement being negotiated between Europe and the United States. PMID- 25138836 TI - Draft code is 'patronising' and too long, says RCN. AB - A proposed new code of practice for nurses drawn up by the Nursing and Midwifery Council (NMC) has been criticised as 'prescriptive and patronising' by the RCN. PMID- 25138837 TI - Unions considering joint action in the autumn over pay award. AB - Thousands of NHS nurses, midwives and other staff may walk out of work for four hours in mid-October in a protest over pay. PMID- 25138839 TI - As you were in first world war nursing. AB - Nursing students dressed up in uniforms from 100 years ago to commemorate the contribution of healthcare workers in the first world war. PMID- 25138840 TI - All hospitals need i.v. therapy lead to reduce incidents, advises NICE. AB - Every hospital should appoint a lead for intravenous (i.v.) fluids to reduce the frequency of complications occurring, says a new quality standard published last week by the National Institute for Health and Clinical Excellence (NICE). PMID- 25138842 TI - Yacker trackers could help keep noise down on wards. AB - A hospital in Australia may introduce 'yacker trackers'--devices that alert staff when there is excessive noise. PMID- 25138843 TI - Medication review saves nurses' time. AB - A project involving care home nurses that led to a significant reduction in unnecessary prescribing has saved around an hour a day of nursing time. PMID- 25138844 TI - Audit uncovers weak skill mix. AB - More than a quarter of hospital wards in Wales do not have the nursing skill mix recommended by the chief nursing officer, according to an audit. PMID- 25138845 TI - NSPCC tests staff values at mental health trust. AB - A child protection charity is training NHS recruiters to recognise which nurses are compassionate and caring enough to employ. PMID- 25138847 TI - Meet Jon Billings, the man charged with modernising the NMC's image. AB - For the past year and a half the Nursing and Midwifery Council (NMC) has been a hive of activity as it tries to repair its tarnished reputation. Barely a month goes by without nurses being consulted on some proposed change, a requirement under the NMC's governing legislation. PMID- 25138853 TI - Bariatric surgery. AB - Essential facts: Type 2 diabetes is linked closely to obesity. Bariatric surgery can lead to dramatic improvements in the management of the condition, according to the National Institute for Health and Care Excellence (NICE). There are two main types of bariatric surgery. A gastric band procedure uses a band to reduce the size of the stomach so a smaller amount of food is required to make the patient feel full. A gastric bypass is where the digestive system is re-routed past most of the stomach so less food is digested. PMID- 25138854 TI - Loosening the belt on weight loss procedures. PMID- 25138855 TI - From NHS to army--and back again. PMID- 25138869 TI - Help for overseas nurses unable to obtain supervised placements. AB - Nurses from outside the European Economic Area looking to work in the UK will no longer have to complete supervised practice placements (News August 6). PMID- 25138868 TI - The NMC is taking too long to process overseas applications. AB - As acting head of nursing and midwifery education at Portsmouth Hospitals NHS Trust, I would like to comment on 'Supervised placements will be scrapped for staff coming to the UK' (News August 6). PMID- 25138870 TI - If hospital nurses are to lose weight, the NHS needs to provide more food. AB - The focus on food in hospitals is invariably on the patients. So it is good to read that NHS England chief executive Simon Stevens is concerned by rising obesity rates and the health of his employees (Analysis August 13). PMID- 25138871 TI - Fill in our survey to help foster a culture of health and fitness. AB - On behalf of the University of Aberdeen, I am inviting nurses to complete an online national survey on the influences on their eating and physical activity for managing body weight. PMID- 25138873 TI - Seacole Statue Appeal reaches another important milestone. AB - As associate director of the NHS Confederation, I am delighted to have been appointed an ambassador for the Mary Seacole Statue Appeal. PMID- 25138874 TI - A renationalised health service would drive down supply costs. AB - 'Politicians alienate nurses at their peril' and 'L32 for 100 wipes--what a waste of NHS money' (Editorial and News July 30) highlight poor procurement policies in the NHS. PMID- 25138875 TI - End of life care services for patients with heart failure. AB - Heart failure has high incidence and prevalence in the UK. However, access to palliative care services for patients with heart failure is inequitable. Patients with heart failure often do not receive specialist palliative care at the end of life, or referral is made only in the last days of life. This results in lost opportunities for advance care planning, psychological support for patients and families and symptom management. Prognostic tools are useful in ensuring appropriate referral. However, the controversy regarding the Liverpool Care Pathway has created uncertainty for healthcare professionals, patients and families. This article examines palliative care and end of life care services for patients with heart failure. It presents the case for service development and examines the benefits for patients who traditionally may not have had access to this care. PMID- 25138876 TI - A parent information leaflet to promote mental health in children. AB - Positive mental health is an essential element of every child's overall health and lays the building blocks for mentally healthy adults. There is increasing emphasis on childhood mental health as a public health issue. Nurses should be able to provide parents with clear, practical and accurate information to promote and maintain positive childhood mental health. This article describes the background to, and development and piloting of, My Mind Matters Too, a parent information leaflet promoting positive mental health for young children. The leaflet cannot operate in a vacuum but must be combined with other services and interventions if it is to bring about changes in the often complex area of childhood mental health. PMID- 25138877 TI - Psychological interventions in obsessive compulsive disorder. AB - Obsessive compulsive disorder (OCD) is a common mental health problem associated with poor quality of life, impaired functioning and increased risk of suicide. Improvement is unlikely and symptoms will remain chronic unless adequate treatment is provided. National Institute for Health and Care Excellence (2006a) guidelines on the management of OCD, recommend the use of psychological treatments that are based on cognitive behavioural therapy (CBT). Brief treatment forms of CBT are recommended initially and more intensive forms are offered when health gain is not apparent. While the presentation of OCD can be complex, nurses can assist in the recognition and treatment of OCD through additional training or current skills. PMID- 25138878 TI - Statins. AB - While I was aware of the link between high serum cholesterol and cardiovascular disease, I was unaware of the mechanism of atheroma development. The CPD article discussed the role of low-density lipoprotein in the development of atherosclerosis, which I found very interesting. PMID- 25138880 TI - New enticements to return to nursing. AB - There are many benefits of supporting former registered nurses back into practice and on to the Nursing and Midwifery Council register. PMID- 25138879 TI - Carers need care too. AB - NHS staff wellbeing has been high on the agenda since the Boorman review concluded that many organisations made insufficient investment in this area of employee welfare. PMID- 25138883 TI - Student life--a template for good care. AB - A personal philosophy of nursing is a strategy that nurses can use to affirm that their practice is in harmony with their values. PMID- 25138884 TI - Well trained in understanding. AB - Healthcare assistants (HCAs) at Milton Keynes Hospital NHS Foundation Trust have been busy with a series of clinical training programmes run for them by the nearby Open University. PMID- 25138887 TI - A course that allows me to fulfil my dream of nursing. AB - As a mature student with many life experiences, I always wanted to be a nurse, and the opportunity to study at BPP University school of health offered me the chance to fulfil my dream. The university's higher education certificate in health and social care allows students to apply for nurse training. PMID- 25138888 TI - The memory services team. AB - In the award-winning memory services at Cumbria Partnership NHS Foundation Trust in Carlisle, assistant practitioners are an essential part of the team. PMID- 25138889 TI - Being washed by someone is therapeutic... and a treat. AB - When in Istanbul, I visited a hamam, a traditional Turkish bath. I'm familiar with other bathing rituals--steam room, sauna, Jacuzzi--but suspected being washed by someone in front of others was not very British. PMID- 25138890 TI - It is just a matter of application. AB - The Camilla Cavendish review of support worker education was clear that improving the quality of healthcare assistant (HCA) learning is central to delivering safe and effective care. Well trained staff should treat patients well, so the point of education and training must be to support HCAs to deliver effective care. But how to guarantee this? PMID- 25138891 TI - Going the extra mile for patients. AB - Just 14 months after she changed career to become a healthcare assistant, Dot O'Meara was presented with one of East Lancashire Hospitals NHS Trust's ten unsung hero awards, writes Carol Davis, freelance journalist. PMID- 25138892 TI - Addressing dehydration. AB - Maintaining an adequate fluid intake is vital for health. Under normal circumstnces, humans require about 2.5 litres of fluid per day. Dehydration occurs when the body loses more fluid than it takes in, and can be the result of either inadequate fluid intake or excessive fluid loss. PMID- 25138893 TI - Legal advice. Richard Griffith on the Mental Capacity Act. AB - Frequently, I am asked by healthcare assistants (HCAs) what the Mental Capacity Act 2005 has to do with their practice as they are not concerned with formal assessments of decision-making capacity or determinations of patients' best interests. PMID- 25138894 TI - Prevalence and characterization of small tympanic bone spicules and drumstick like hyperostotic tympanic bone spicules in the middle ear cavity of dogs. AB - Rounded, sessile, hyperattenuating structures detected in computed tomography (CT) studies of canine tympanic bullae have been termed "otoliths." These have been proposed to represent dystrophic mineralizations or heterotopic bone formations in the middle ear that are potentially related to chronic otitis media. Aims of the current study were to describe the prevalence, macroscopic, and histological features of structures consistent with "otoliths" in the canine tympanic cavity. Tympanic bullae from 50 routinely necropsied dogs and 139 retrospectively retrieved CT scans of canine clinical cases were examined. Small tympanic bone spicules with pointed or clubbed tips essentially arising from the free margin of the septum bullae were bilaterally present in the tympanic cavities of all 50 of the necropsied dogs. In 48% of the dogs, "otolith"-like CT detectable bone spicules carrying drumstick-like hyperostoses that were 1-6 mm in diameter were also present. In the retrospective survey of bulla CT scans of 139 cases, the prevalence of hyperostotic tympanic bone spicules (HTBS) was 20%. Findings from the current study indicated that the presence of small tympanic bone spicules in adult dogs is most likely due to physiological bone growth in the septum bullae and that HTBS represent osseous proliferations of small tympanic bone spicules. However, the factors inducing formation of hyperostotic spicules from small tympanic bone spicules remain unknown. The high prevalence of HTBS displaying a similar appearance in bulla CT scans in dogs suggests that these spicules should be included in a differential diagnosis list for "otoliths." PMID- 25138895 TI - Validation of the German version of the Clinical Assessment Interview for Negative Symptoms (CAINS). AB - Validated assessment instruments could contribute to a better understanding and assessment of negative symptoms and advance treatment research. The aim of this study was to examine the psychometric properties of a German version of the Clinical Assessment Interview for Negative Symptoms (CAINS). In- and outpatients (N=53) with schizophrenia or schizoaffective disorder were assessed with standardized interviews and questionnaires on negative and positive symptoms and general psychopathology in schizophrenia, depression, the ability to experience anticipatory and consummatory pleasure, and global functioning. The results indicated good psychometric properties, high internal consistency and promising inter-rater agreement for the German version of the CAINS. The two-factor solution of the original version of the CAINS was confirmed, indicating good construct validity. Convergent validity was supported by significant correlations between the CAINS subscales with the negative symptom scale of the Positive and Negative Syndrome Scale, and with consummatory pleasure. The CAINS also exhibited discriminant validity indicated by its non-significant correlations with positive symptoms, general psychopathology and depression that are in line with the findings for the original version of the CAINS. In addition, the CAINS correlated moderately with global functioning. The German version of the CAINS appears to be a valid and suitable diagnostic tool for measuring negative symptoms in schizophrenia. PMID- 25138896 TI - A phenomenological investigation of overvalued ideas and delusions in clinical and subclinical anorexia nervosa. AB - Anorexia Nervosa (AN) is an eating disorder characterised by distorted cognitions about body weight and shape; but little is known about the phenomenological characteristics of these beliefs. In this study, multidimensional and insight based measurements were used to compare beliefs about body weight and shape in AN to body image dissatisfaction in the general population, and delusional beliefs in schizophrenia. Twenty participants with clinical and sub-clinical AN, 27 participants with schizophrenia and schizoaffective disorder, and 23 healthy controls completed the Brown Assessment of Beliefs Scale and the Psychotic Symptom Rating Scale in relation to a dominant belief regarding body weight/shape (or body dissatisfaction in healthy controls) or a current delusion. All groups completed the Peters Delusions Inventory to assess the prevalence of a range of delusion-like beliefs. Participants with clinical and subclinical AN experienced significantly higher preoccupation and distress for their belief in comparison to both participants with schizophrenia/schizoaffective disorder rating a delusional belief and the healthy controls rating a belief of body dissatisfaction. Both clinical groups were comparable on ratings of belief conviction and disruption. The data raise questions regarding the current frameworks that are used to describe beliefs in AN. PMID- 25138897 TI - Epidemiology of dengue in a high-income country: a case study in Queensland, Australia. AB - BACKGROUND: Australia is one of the few high-income countries where dengue transmission regularly occurs. Dengue is a major health threat in North Queensland (NQ), where the vector Aedes aegypti is present. Whether NQ should be considered as a dengue endemic or epidemic region is an ongoing debate. To help address this issue, we analysed the characteristics of locally-acquired (LA) and imported dengue cases in NQ through time and space. We describe the epidemiology of dengue in NQ from 1995 to 2011, to identify areas to target interventions. We also investigated the timeliness of notification and identified high-risk areas. METHODS: Data sets of notified cases and viraemic arrivals from overseas were analysed. We developed a time series based on the LA cases and performed an analysis to capture the relationship between incidence rate and demographic factors. Spatial analysis was used to visualise incidence rates through space and time. RESULTS: Between 1995 and 2011, 93.9% of reported dengue cases were LA, mainly in the 'Cairns and Hinterland' district; 49.7% were males, and the mean age was 38.0 years old. The sources of imported cases (6.1%) were Indonesia (24.6%), Papua New Guinea (23.2%), Thailand (13.4%), East Timor (8.9%) and the Philippines (6.7%), consistent with national data. Travellers importing dengue were predominantly in the age groups 30-34 and 45-49 years old, whereas the age range of patients who acquired dengue locally was larger. The number of LA cases correlated with the number of viraemic importations. Duration of viraemia of public health importance was positively correlated with the delay in notification. Dengue incidence varied over the year and was typically highest in summer and autumn. However, dengue activity has been reported in winter, and a number of outbreaks resulted in transmission year-round. CONCLUSIONS: This study emphasizes the importance of delay in notification and consequent duration of viraemia of public health importance for dengue outbreak duration. It also highlights the need for targeted vector control programmes and surveillance of travellers at airports as well as regularly affected local areas. Given the likely increase in dengue transmission with climate change, endemicity in NQ may become a very real possibility. PMID- 25138898 TI - Dynamics of bovine opsin bound to G-protein fragments. AB - G protein-coupled receptors (GPCRs) are a large class of membrane proteins that mediate communication of the cell with the outer environment. Upon activation by an agonist, GPCRs undergo large-scale conformational changes that enable binding of the G protein to the receptor. A key open question concerns the mechanism of the long-distance coupling between the agonist-binding site and the cytoplasmic site where G protein binds. Here we address this question by exploring the molecular dynamics of bovine opsin bound to three different fragments of G proteins. We find that an extended network of hydrogen bonds connects the agonist retinal binding site to the G protein binding site via conserved amino acid residues. The dynamics of the hydrogen-bonding network inside opsin couples to interactions at the G protein binding site. PMID- 25138899 TI - Survival trends among patients with advanced renal cell carcinoma in the United States. AB - INTRODUCTION: Since the approval of sorafenib in December 2005, several targeted therapeutic agents have been approved by the FDA for the treatment of advanced renal cell carcinoma (RCC). This study was conducted to find out whether the improvements in survival of advanced RCC patients with targeted agents have translated into a survival benefit in a population-based cohort. METHODS: We analyzed the SEER 18 (Surveillance, Epidemiology and End RESULTS) registry database to calculate the relative survival rates for advanced RCC patients during 2001-2009, 2001-2005, 2006-2007 and 2008-2009. We also evaluated the survival rates by age (<65 and >=65 years) and sex. RESULTS: The total number of advanced RCC patients during 2001-2009, 2001-2005, 2006-2007 and 2008-2009 were 7,047, 4,059, 1,548 and 1,440, respectively. During 2001-2009, the 1- and 3-year relative survival rates were 26.7+/-0.6 and 10.0+/-0.4%, respectively. There was no significant difference in 1-year relative survival rates for patients diagnosed during 2006-2007 and 2008-2009 compared to those diagnosed during 2001 2005. Similarly, the 3-year survival rates for patients diagnosed during 2006 2007 were similar to those diagnosed during 2001-2005. CONCLUSIONS: This population-based study showed that there was no significant improvement in relative survival rates among advanced RCC patients in the era of targeted agents. PMID- 25138900 TI - Current opinion on optimal systemic treatment for metastatic colorectal cancer: outcome of the ACTG/AGITG expert meeting ECCO 2013. AB - The treatment of metastatic colorectal cancer has evolved greatly in the last 15 years, involving combined chemotherapy protocols and, in more recent times, new biologic agents. Clinical benefit from the use of targeted therapy with bevacizumab, aflibercept, cetuximab, panitumumab and regorafenib in the treatment of metastatic colorectal cancer is now well established with median overall survival accepted as over 24 months, and with super selection for extended RAS patients higher again. The optimal timing of treatment options requires careful consideration of predictive biomarkers, and importantly the potential for interactions, to derive the maximal benefit. A group of colorectal subspecialty medical oncologists from Australia, the USA, the Netherlands and Germany met during ECCO 2013 to discuss current practice. Subsequent new data from the American Society of Clinical Oncology were also reviewed. This article reviews the evidence discussed in support of modern treatments for colorectal cancer and the decision-making behind the treatment choices, with their benefits and risks. PMID- 25138901 TI - Effect of omeprazole dose, nonsteroidal anti-inflammatory agents, and smoking on repair mechanisms in acute peptic ulcer bleeding. AB - BACKGROUND: Peptic ulcer bleeding (PUB) is a major cause of upper gastrointestinal bleeding. The effect of omeprazole on mucosal repair is unknown. AIMS: We studied the effect of omeprazole, nonsteroidal anti-inflammatory agents, and smoking on PUB. METHODS: There were 43 PUB patients who received regular or high dose of omeprazole for 72 h. Biopsies from antrum and corpus were taken before and after treatment. Biopsy samples from 20 celiac disease patients worked as controls. The expression of Ki-67, Bcl-2, COX-2, Hsp27, and Hsp70 was analyzed from patients and controls. RESULTS: Bcl-2 expression in PUB patients was lower than in controls. However, Bcl-2 increased significantly from 5.0 (SD 4.5) to 9.1 % (SD 6.7), p = 0.0004, in the antrum after omeprazole. In univariate analysis, a high omeprazole dose caused a more profound increase in Ki-67 expression in the corpus: 35.3 % (SD 54.8) than a regular dose: -10.1 % (SD 40.6), p = 0.022. In multivariate analysis, Ki-67 decreased significantly in the corpus between the pre- and posttreatment period (p = 0.011), while a high omeprazole dose (p = 0.0265), the use of NSAIDs (p = 0.0208), and smoking (p = 0.0296) significantly increased Ki-67 expression. Bcl-2 in the corpus increased significantly (p = 0.0003) after treatment. CONCLUSIONS: Our findings suggest that Bcl-2 may be an important factor in the pathogenesis of a peptic ulcer and PUB. In addition, high dose omeprazole increased the expression of Ki-67, which may enhance the healing process of a peptic ulcer. PMID- 25138902 TI - Endoclips to facilitate cannulation and sphincterotomy during ERCP in a patient with an ampulla within a large duodenal diverticulum: case report and literature review. PMID- 25138903 TI - Acute fatty liver of pregnancy treated with plasma exchange. PMID- 25138904 TI - Non-MalIg(G4)nant Biliary Obstruction: When the Pill Is Mightier than the Knife. PMID- 25138905 TI - More with less: pancreas-preserving total duodenectomy. PMID- 25138906 TI - Public supply well vulnerability. PMID- 25138907 TI - Cyantraniliprole: a valuable tool for Frankliniella occidentalis (Pergande) management. AB - BACKGROUND: Frankliniella occidentalis is a worldwide economically important pest. Scarcity of effective products and cross-resistance issues make resistance to existing insecticides a recurring problem that requires the development of new control tools, such as incorporating novel compounds. Lethal effects of cyantraniliprole on adults and larvae from field and insecticide-resistant populations were evaluated. In addition, the sublethal effects on biological features such as fecundity, fertility, feeding, oviposition and mating were studied. RESULTS: Results obtained for larvae produced LC50 values ranging from 33.4 to 109.2 mg L(-1) , with a low natural variability (3.3-fold) and a LC50 composite value of 52.2 mg L(-1) . The susceptibility for adults was 23-fold lower than for larvae. No evidence of cross-resistance between cyantraniliprole and established insecticides used against thrips was evident. Relevant sublethal effects of cyantraniliprole were demonstrated, including reduced fecundity, fertility, feeding, oviposition and mating success. CONCLUSION: Low variation in susceptibility across contemporary populations of F. occidentalis and a lack of cross-resistance to other insecticides indicate that cyantraniliprole is a potential candidate in rotation programmes within an insecticide resistance management strategy. The combined sublethal effect on reproduction will have an important impact on population reduction. Available data indicate that cyantraniliprole is likely to be a valuable tool for managing thrips populations. PMID- 25138909 TI - China's 50% caesarean delivery rate: is it too high? PMID- 25138908 TI - MG428 is a novel positive regulator of recombination that triggers mgpB and mgpC gene variation in Mycoplasma genitalium. AB - The human pathogen Mycoplasma genitalium employs homologous recombination to generate antigenic diversity in the immunodominant MgpB and MgpC proteins. Only recently, some of the molecular factors involved in this process have been characterized, but nothing is known about its regulation. Here, we show that M. genitalium expresses N-terminally truncated RecA isoforms via alternative translation initiation, but only the full-length protein is essential for gene variation. We also demonstrate that overexpression of MG428 positively regulates the expression of recombination genes, including recA, ruvA, ruvB and ORF2, a gene of unknown function co-transcribed with ruvAB. The co-ordinated induction of these genes correlated with an increase of mgpBC gene variation. In contrast, cells lacking MG428 were unable to generate variants despite expressing normal levels of RecA. Similarly, deletion analyses of the recA upstream region defined sequences required for gene variation without abolishing RecA expression. The requirement of these sequences is consistent with the presence of promoter elements associated with MG428-dependent recA induction. Sequences upstream of recA also influence the relative abundance of RecA isoforms, possibly through translational regulation. Overall, these results suggest that MG428 is a positive regulator of recombination and that precise control of recA expression is required to initiate mgpBC variation. PMID- 25138910 TI - Attentional load interferes with target localization across saccades. AB - The retinal positions of objects in the world change with each eye movement, but we seem to have little trouble keeping track of spatial information from one fixation to the next. We examined the role of attention in trans-saccadic localization by asking participants to localize targets while performing an attentionally demanding secondary task. In the first experiment, attentional load decreased localization precision for a remembered target, but only when a saccade intervened between target presentation and report. We then repeated the experiment and included a salient landmark that shifted on half the trials. The shifting landmark had a larger effect on localization under high load, indicating that observers rely more on landmarks to make localization judgments under high than under low attentional load. The results suggest that attention facilitates trans-saccadic localization judgments based on spatial updating of gaze-centered coordinates when visual landmarks are not available. The availability of reliable landmarks (present in most natural circumstances) can compensate for the effects of scarce attentional resources on trans-saccadic localization. PMID- 25138911 TI - Object ownership and action: the influence of social context and choice on the physical manipulation of personal property. AB - Understanding who owns what is important for guiding appropriate action in a social context. Previously, we demonstrated that ownership influences our kinematic patterns associated with hand-object interactions (Constable et al. in Cognition 119(3):430-437, 2011). Here, we present a series of experiments aimed at determining the underlying mechanisms associated with this effect. We asked participants to lift mugs that differed in terms of ownership status (Experiments 1 and 2) and personal preference (Experiment 3) while recording spatial and acceleration measures. In Experiment 1, participants lifted their own mug with greater acceleration and drew it closer to themselves than they did the experimenter's mug. They also lifted the experimenter's mug further to the right compared with other mugs. In Experiment 2, spatial trajectory effects were preserved, but the acceleration effect abolished, when the owner of the 'other owned' mug was a known-but absent-confederate. Experiment 3 demonstrated that merely choosing to use a mug was not sufficient to elicit rightward drift or acceleration effects. We suggest that these findings reflect separate and distinct mechanisms associated with socially related visuomotor processing. PMID- 25138912 TI - Vestibular evoked potentials (VsEPs) of cortical origin produced by impulsive acceleration applied at the nasion. AB - We report the results of a study to record vestibular evoked potentials (VsEPs) of cortical origin produced by impulsive acceleration (IA). In a sample of 12 healthy participants, evoked potentials recorded by 70 channel electroencephalography were obtained by IA stimulation at the nasion and compared with evoked potentials from the same stimulus applied to the forefingers. The nasion stimulation gave rise to a series of positive and negative deflections in the latency range of 26-72 ms, which were dependent on the polarity of the applied IA. In contrast, evoked potentials from the fingers were characterised by a single N50/P50 deflection at about 50 ms and were polarity invariant. Source analysis confirmed that the finger evoked potentials were somatosensory in origin, i.e. were somatosensory evoked potentials, and suggested that the nasion evoked potentials plausibly included vestibular midline and frontal sources, as well as contributions from the eyes, and thus were likely VsEPs. These results show considerable promise as a new method for assessment of the central vestibular system by means of VsEPs produced by IA applied to the head. PMID- 25138913 TI - Revisiting the association between hypnotisability and blink rate. AB - Blink rate (BR), which is considered an index of the dopaminergic tone, has been studied in 41 subjects with high (highs), medium (mediums) and low (lows) hypnotisability scores in resting conditions. It has been found higher in highs; relaxation (indicated by skin conductance), anxiety and the proneness to absorption in tasks (assessed by questionnaires) were not responsible for the observed difference. In contrast, the BR difference did not survive controlling for mind wandering (MW questionnaire) whose variability could account for contrasting earlier reports, although no significant hypnotisability-related difference has been observed in MW scores. Findings do not allow to exclude that mechanisms other than dopaminergic ones may be involved in the observed difference in BR. In particular, we suggest that one of the mechanisms possibly sustaining the highs' higher BR may be a reduced cerebellar inhibition. In fact, cerebellar impairment is associated with higher BR and several studies of sensorimotor integration indicate different cerebellar controls in the highs' and lows' behavior. PMID- 25138914 TI - Sodium-assisted formation of binding and traverse conformations of the substrate in a neurotransmitter sodium symporter model. AB - Therapeutics designed to increase synaptic neurotransmitter levels by inhibiting neurotransmitter sodium symporters (NSSs) classify a strategic approach to treat brain disorders such as depression or epilepsy, however, the critical elementary steps that couple downhill flux of sodium to uphill transport of neurotransmitter are not distinguished as yet. Here we present modelling of NSS member neuronal GAT1 with the substrate γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter. GABA binding is simulated with the occluded conformation of GAT1 homodimer in an explicit lipid/water environment. Simulations performed in the 1-10 ns range of time elucidated persistent formation of halfextended minor and H-bridged major GABA conformations, referred to as binding and traverse conformations, respectively. The traverse GABA conformation was further stabilized by GAT1-bound Na(+)(1). We also observed Na(+)(1) translocation to GAT1-bound Cl(-) as well as the appearance of water molecules at GABA and GAT1 bound Na(+)(2), conjecturing causality. Scaling dynamics suggest that the traverse GABA conformation may be valid for developing substrate inhibitors with high efficacy. The potential for this finding is significant with impact not only in pharmacology but wherever understanding of the mechanism of neurotransmitter uptake is valuable. PMID- 25138915 TI - Feasibility study of a new RF coil design for prostate MRI. AB - The combined use of a torso-pelvic RF array coil and endorectal RF coil is the current state-of-the-art in prostate MRI. The endorectal coil provides high detection sensitivity to acquire high-spatial resolution images and spectroscopic data, while the torso-pelvic coil provides large coverage to assess pelvic lymph nodes and pelvic bones for metastatic disease. However, the use of an endorectal coil is an invasive procedure that presents difficulties for both patients and technicians. In this study, we propose a novel non-invasive RF coil design that can provide both image signal to noise ratio and field of view coverage comparable to the combined torso-pelvic and endorectal coil configuration. A prototype coil was constructed and tested using a pelvic phantom. The results demonstrate that this new design is a viable alternative for prostate MRI. PMID- 25138918 TI - Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions. AB - BACKGROUND: Fingolimod is a disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod decreases annual relapse rates and gadolinium enhancing lesions on MRI as compared to either interferon beta (IFNbeta) or placebo. The effect of fingolimod on MRI outcomes compared to natalizumab treatment has not been investigated in (head to head) clinical trials. Clinical experience with natalizumab is much more extended and in general practice often preferred. CASE PRESENTATION: This case describes a 31-year old woman with RRMS, who experienced severe side effects on natalizumab. After a voluntary four months treatment free period, a severe relapse appeared which was treated with prednisone and plasmapheresis; thereafter fingolimod was initiated. In the following months MRI signs improved spectacularly. CONCLUSION: This case suggests that fingolimod might be a good alternative for natalizumab, especially for use in RRMS patients, with highly active, advanced disease, when natalizumab treatment is stopped due to side effects or even after a severe relapse. PMID- 25138919 TI - NMR of solutes in nematic and smectic A liquid crystals: the anisotropic intermolecular potential. AB - Orientational order parameters determined from (1)H NMR spectroscopy of solutes in liquid crystals that form both nematic and smectic A phases are used to determine the solute smectic A order parameters and the smectic-nematic coupling term. For the analysis, it is necessary to know the nematic part of the potential in the smectic A phase: various ways of extrapolating parameters from the nematic phase to the smectic phase are explored. PMID- 25138917 TI - Maternal age and serum concentration of human chorionic gonadotropin in early pregnancy. AB - OBJECTIVE: To study whether maternal age is associated with serum concentration of human chorionic gonadotropin in early pregnancy. DESIGN: Cross-sectional study. SETTING: Oslo University Hospital in Oslo, Norway. POPULATION: All vital pregnancies in gestational week 8 conceived by in vitro fertilization between February 1996 and February 2013 (n = 4472). METHODS: Serum concentrations of human chorionic gonadotropin were measured on day 12 after embryo transfer/day 16 following ovulation induction. Trends in geometric means of human chorionic gonadotropin concentrations by maternal age group were tested by linear regression analysis. We also studied the association of maternal age (years) with log-transformed human chorionic gonadotropin concentrations, and adjustments were made for number of embryos transferred, method of in vitro fertilization and year (period) of embryo transfer. MAIN OUTCOME MEASURE: Serum concentration of human chorionic gonadotropin. RESULTS: Geometric mean concentrations of human chorionic gonadotropin decreased with increasing maternal age (p = 0.024, test for trend by weighted linear regression). Also, we estimated a significant negative association of maternal age with log-transformed human chorionic gonadotropin concentrations (adjusted regression coefficient -0.011, standard error 0.003, p < 0.001). CONCLUSIONS: Serum concentrations of human chorionic gonadotropin in very early pregnancy decreased with maternal age. Since human chorionic gonadotropin is synthesized in trophoblast cells only, the lower human chorionic gonadotropin concentrations in women of advanced age may reflect functional impairment or delayed proliferation of trophoblast cells in early pregnancy in these women. PMID- 25138920 TI - Contending with uncertainty in conservation management decisions. AB - Efficient conservation management is particularly important because current spending is estimated to be insufficient to conserve the world's biodiversity. However, efficient management is confounded by uncertainty that pervades conservation management decisions. Uncertainties exist in objectives, dynamics of systems, the set of management options available, the influence of these management options, and the constraints on these options. Probabilistic and nonprobabilistic quantitative methods can help contend with these uncertainties. The vast majority of these account for known epistemic uncertainties, with methods optimizing the expected performance or finding solutions that achieve minimum performance requirements. Ignorance and indeterminacy continue to confound environmental management problems. While quantitative methods to account for uncertainty must aid decisions if the underlying models are sufficient approximations of reality, whether such models are sufficiently accurate has not yet been examined. PMID- 25138922 TI - Enabling LiTFSI-based electrolytes for safer lithium-ion batteries by using linear fluorinated carbonates as (Co)solvent. AB - In this Full Paper we show that the use of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) as conducting salt in commercial lithium-ion batteries is made possible by introducing fluorinated linear carbonates as electrolyte (co)solvents. Electrolyte compositions based on LiTFSI and fluorinated carbonates were characterized regarding their ionic conductivity and electrochemical stability towards oxidation and with respect to their ability to form a protective film of aluminum fluoride on the aluminum surface. Moreover, the investigation of the electrochemical performance of standard lithium-ion anodes (graphite) and cathodes (Li[Ni1/3 Mn1/3 Co1/3 ]O2 , NMC) in half-cell configuration showed stable cycle life and good rate capability. Finally, an NMC/graphite full-cell confirmed the suitability of such electrolyte compositions for practical lithium-ion cells, thus enabling the complete replacement of LiPF6 and allowing the realization of substantially safer lithium-ion batteries. PMID- 25138923 TI - Characterisation of whisker control in the California sea lion (Zalophus californianus) during a complex, dynamic sensorimotor task. AB - Studies in pinniped whisker use have shown that their whiskers are extremely sensitive to tactile and hydrodynamic signals. While pinnipeds position their whiskers on to objects and have some control over their whisker protractions, it has always been thought that head movements are more responsible for whisker positioning than the movement of the whiskers themselves. This study uses ball balancing, a dynamic sensorimotor skill that is often used in human and robotic coordination studies, to promote sea lion whisker movements during the task. For the first time, using tracked video footage, we show that sea lion whisker movements respond quickly (26.70 ms) and mirror the movement of the ball, much more so than the head. We show that whisker asymmetry and spread are both altered to help sense and control the ball during balancing. We believe that by designing more dynamic sensorimotor tasks we can start to characterise the active nature of this specialised sensory system in pinnipeds. PMID- 25138924 TI - B chromosomes in the grasshopper Eyprepocnemis plorans are present in all body parts analyzed and show extensive variation for rDNA copy number. AB - B chromosomes in the grasshopper Eyprepocnemis plorans are considered to be mitotically stable, because all meiotic (primary spermatocytes and oocytes) or mitotic (embryos, ovarioles, and gastric caecum) cells analyzed within the same individual show the same B chromosome number. Nothing is known, however, about body parts with somatic tissues with no mitotic activity in adult individuals, constituting the immense majority of their body. Therefore, we investigated whether B chromosomes are present in 8 non-mitotically active somatic body parts from both sexes in addition to ovarioles and testes by PCR analysis of 2 B specific molecular markers. We also elucidated the number of B chromosomes that an individual carried through quantifying the B-located rDNA copy number by qPCR. Our results indicated the amplification of both B-specific markers in all analyzed body parts. However, we found high variation between males for the estimated number of rDNA units in the B chromosomes. These results demonstrate the presence of B chromosomes in all body parts from the same individual and suggest a high variation in the rDNA content of the B chromosomes carried by different individuals from the same population, presumably due to unequal crossovers during meiosis. PMID- 25138926 TI - [Echocardiography]. AB - Assessment of ischemic mitral regurgitation( IMR) severity is important to stratify patients' management. Because IMR is influenced by loading condition seriously, it is difficult to evaluate severity of IMR in clinically stable condition at rest. Exercise stress echocardiography is useful tool to assess "true" severity of IMR. Recently, mitral valve plasty( undersized annuloplasty) creates a new problem, which is called "functional mitral stenosis". Exercise stress echocardiography also reveals this hemodynamics. Recent 3-dimensional (3D) echocardiography enables an intuitive understanding a valve anatomy by surgeon's view, and a more detailed quantitative evaluation. The 3D echocardiography can contribute to exact valve area calculation and can evaluate the forms of the valve ring which had difficulty in evaluation by 2D echocardiography. The treatment of structural heart disease with catheter has been introduced, and therefore the importance of the 3D echocardiography increases in this field. In this review, we describe the role of stress echocardiography on the assessment of IMR and the current status of 3D echocardiography. PMID- 25138927 TI - [Role of cardiac computed tomography in cardiac surgery]. AB - In the field of cardiovascular surgery, cardiac computed tomography (CT) has served an important role in association with the improvement of the spatial and temporal resolution. Because CT angiography (CTA) provides more available information than plain CT, CTA has been increasingly used to access the coronary arteries and graft patency after coronary artery bypass grafting (CABG). Recently, minimally invasive cardiac surgeries, including CABG with left mini thoracotomy and mitral valve surgery with right mini-thoracotomy, are revived, which requires preoperative CTA to make a strategy of incision placement on the basis of anatomical relationship between the target structure of the heart and the thorax. In Japan, transcatheter aortic valve implantation (TAVI) was approved in the late 2013, and is expected to be widely performed in the future. CTA is extremely useful for TAVI patients to determine the choice of the valve size and the surgical approach. CT provides many other valuable findings to us, but if we cannot fully leverage it in the daily cardiovascular surgery, its value is decreased. We have to acquire enough skill to maximize the performance of CT in the practical clinical setting. PMID- 25138928 TI - [Cardiovascular magnetic resonance imaging]. AB - Cardiac magnetic resonance imaging (CMR) evolves and is occupying an important status in cardiovascular diagnostic imaging. In particular, in the estimation of the cause of heart failure, or evaluation of severity-of-illness and prognostic presumption, utility is high clinically. In this chapter, about a selection sequence for taking image according to the purpose, description of findings, and its clinical utility are introduced. And the role which this imaging plays will be discussed in the near future. PMID- 25138930 TI - [Evoked potentials monitoring in aortic surgery]. AB - Somatosensory evoked potential (SSEP), evoked spinal cord potential (ESCP) and motor evoked potential (MEP) have been used to detect spinal cord ischemia during aortic surgery. SSEP evaluates the sensory pathway, and is recorded from the sensory cortex by peripheral nerve stimulation. The interval from the onset of ischemia to change is relatively long(5-10 minutes). It has less frequently been used because of the high false negative and false positive rate. ESCP is recorded from the spinal cord by direct stimulation of the cord. It reflects the function of spinal tract but not that of alpha motor neurons. It is resistant to anesthesia and both the sensitivity and specificity is high, but the interval from ischemia to change is relatively long. Together with the necessity of 2 epidural electrodes, its application in aortic surgery has become infrequent. Since the introduction of train pulse transcranial electrical stimulation, myogenic MEP have gained widespread acceptance. It evaluates motor pathways from the cortex to the muscle, and therefore is influenced by non-spinal factors such as peripheral nerve ischemia. Its vulnerability to anesthesia requires special anesthetic consideration, and baseline amplitude fluctuation is common. It is highly sensitive and shows changes in the early phase of spinal cord ischemia. PMID- 25138929 TI - [Cerebral blood flow monitoring]. AB - Cerebral ischemic events remain a major problem in patients undergoing cardiac and thoracic aortic surgery. Efforts to improve outcomes have been made in many aspects which include cerebral monitoring. New technology is making it possible to shed a light to the brain, which historically used to be a black box during general anesthesia in the operating room. Cerebral brain monitoring methods include cerebral oxymetry using near infrared spectroscopy, trans cranial Doppler, Jugular venous oxygen saturation, bispectral index, temporal artery pressure monitoring. Cerebral oxymetry probably is the most commonly used method among these based on its simplicity and reproducibility. Though it is easy to obtain numbers from cerebral oxymetry, it is important to understand the principle and the limitations to interpret the results, properly. PMID- 25138931 TI - [How to use assist devices effectively in off-pump coronary artery bypass surgery]. AB - Off-pump coronary artery bypass is a technically demanding procedure, which is, however, widely performed in Japan. In this paper, most widely used assist devices such as tissue stabilizers, heart positioners, intraluminal coronary artery shunts and proximal anastomosis assist devices are introduced along with tips of usage. PMID- 25138932 TI - [Overview of ablation devices for atrial fibrillation surgery]. AB - Since Cox-maze procedure was first reported in 1987, ablation technology has made great progress and revolutionized atrial fibrillation surgery. Various energy sources have been introduced to facilitate creating conduction block within the atria. These sources include radiofrequency, cryothermia, microwave, laser, and high-frequency focused ultrasound( HIFU). They have been utilized both endocardially in the arrested heart and epicardially in the beating heart. The goal of all these sources is to create transmural lesions which enable irreversible conduction block. They have been reported to have clinical efficacy, but each of them have their own advantages and disadvantages, and their ability of creating transmural lesions are also different. It is important for surgeons that they fully understand these differences to make appropriate use of these technologies for achieving safe atrial fibrillation surgery and developing less invasive new procedures. PMID- 25138933 TI - [Intraaortic balloon pumping( IABP) in Japan]. AB - The intraaortic balloon pumping (IABP) is the most widely used circulatory assist device. IABP increases coronary perfusion in diastolic phase by the inflation of the balloon in the descending aorta (diastolic augmentation) and reduces afterload in systolic phase by the deflation of the balloon( systolic unloading). IABP improves the hemodynamic condition of patients who fall into acute heart failure and/or cardiogenic shock. Six-type IABP system can be used in Japan. The IABP-SHOCK II trial shows that there is no significant difference in mortality between optimal medical treatment with IABP and without IABP in addition to early revascularization. Clinical backgrounds in Japan are different from those in IABP SHOCK II trial, and the further prospective studies of IABP in Japan thus called for. PMID- 25138934 TI - [Fundamental features on percutaneous cardiopulmonary support]. AB - The fundamental features on percutaneous cardiopulmonary support (PCPS) were reviewed. The number of PCPS installation in Japan has been increasing especially in the area of emergency medicine and cardiology. All-in-one package for PCPS system is becoming a mainstream in clinical practice. It is considered to be crucial to understand the details in characteristics and pitfalls on respective products. The results of nation-wide questionnaire indicate that the detailed criteria for PCPS usage in clinical practice appear to be variable among facilities in Japan;therefore, the formulation of guideline and educational system for PCPS installation is required. PMID- 25138935 TI - [Implantable ventricular assist device]. AB - Implantable ventricular assist device( VAD) is the only evidence-based option to treat stage D heart failure patients with significant symptoms at rest in spite of maximum medical therapy, other than heart transplant. Implantable VADs available in Japan include Evaheart, DuraHeart both from Japan, Jarvik 2000 and HeartMate II both from United States. In Japanese settings, implantable VAD is indicated and insured only for patients who are supposed to have an indication for receiving heart transplant, which means "bridge to transplantation" use. And in Japan, implantable VAD can be implanted for patients less than 65 years old if it needs to be insured. In the University of Tokyo Hospital, the mid-term outcomes of 41 implantable VAD patients were acceptable with 2 hospital deaths, 2 remote deaths and one year survival rate at 88%.Considering the present Japanese situation with extreme shortage of organ donation, the extended application of implantable VADs as "Destination Therapy" is awaited, but quality of life of care givers as well as patients themselves and sustainable follow-up system provided by healthcare professionals need to be warranted. PMID- 25138937 TI - [Thoracic endovascular aneurysm repair]. AB - Endovascular aneurysm repair has brought revolution in the treatment of aortic disease. Although surgical treatment for thoracic aortic aneurysm impose large invasiveness on patients of aged population, endovascular aneurysm repair supply extreme less-invasive treatment for patients with thoracic aortic disease, because of unnecessary for thoracotomy and extracorporeal circulation. Thoracic endovascular aneurysm repair will have further applications and distributions with development and improvement of the device. PMID- 25138936 TI - [Annuloplasty ring and band for valve repair]. AB - Annulus dilatation is present in almost all patients with mitral regurgitation, tricuspid regurgitation. Therefore annuloplasty is required to obtain normal leaflet coaptation. Annuloplasty ring or band offers more stability in valve repair, improving long-term outcome. Since annuloplasty ring and band of various types can be used, to understand the characteristics and to select proper size are important. PMID- 25138938 TI - [Transcatheter aortic valve replacement]. AB - While transcatheter aortic valve replacement( TAVR) has spread rapidly all over the world for highrisk patients with severe aortic stenosis (AS), SAPIEN XT was approved in Japan in October 2013. Since that, approximately 400 TAVR cases were performed in Japan. In our institute, we have performed 164 cases since first case in Japan in 2009 and have achieved satisfactory early results(30-day mortality:1.2%). At the same time, however, simultaneously various TAVR-related complications including a paravalvular leak, stroke, vascular complications, and coronary obstruction were observed. A reduction in the incidence and severity of these complications had led technical improvements in various new devices(2nd generation TAVR device such as the SAPIEN 3, ACURATE, and JenaValve) and in implantation techniques including repositioning/recapturing features, paravalvular sealing technologies, and prevention of coronary obstruction. Furthermore, there is also increasing experience with special indications for TAVR such as pure aortic valve insufficiency or valve-in-valve techniques. Currently, an increasing number of publications of midterm results demonstrate good prosthetic valve function and durability, with good quality of life and low morbidity after TAVR. There are also some randomized trials such as PARTNER 2 or SURTAVI to investigate potential benefits of TAVR for intermediate-risk patients. These improvements in the TAVR devices promises the expansion of TAVR towards the treatment of lower-risk patients in the near future. PMID- 25138939 TI - [da Vinci surgical system]. AB - The da Vinci surgical system was developed by Intuitive Surgical Inc. in the United States as an endoscopic surgical device to assist remote control surgeries. In 1998, the Da Vinci system was first used for cardiothoracic procedures. Currently a combination of robot-assisted internal thoracic artery harvest together with coronary artery bypass grafting (CABG) through a mini incision (ThoraCAB) or totally endoscopic procedures including anastomoses under robotic assistance (TECAB) are being conducted for the treatment of coronary artery diseases. With the recent advances in catheter interventions, hybrid procedures combining catheter intervention with ThoraCAB or TECAB are anticipated in the future.On the other hand, with the decrease in number of coronary artery bypass surgeries, the share of valvular surgeries is expected to increase in the future. Among them, mitral valvuloplasty for mitral regurgitation is anticipated to be conducted mainly by low-invasive procedures, represented by minimally invasive cardiac surgery( MICS) and robot-assisted surgery. Apart from the intrinsic good surgical view, robotic-assisted systems offer additional advantages of the availability of an amplified view and the easy to observe the mitral valve in the physiological position. Thus, robotic surgical surgeries that make complicated procedures easier are expected to accomplish further developments in the future. Furthermore, while the number of surgeries for atrial septal defects has decreased dramatically following the widespread use of Amplatzer septal occluder, robotic surgery may become a good indication for cases in which the Amplatzer device is not indicated. In Japan, clinical trial of the da Vinci robotic system for heart surgeries has been completed. Statutory approval of the da Vinci system for mitral regurgitation and atrial septal defects is anticipated in the next few years. PMID- 25138940 TI - [Percutaneous edge-to-edge repair using the MitraClip system]. AB - Percutaneous edge-to-edge repair with the MitraClip system has emerged as a new therapeutic option for moderate to severe or severe mitral regurgitation (MR). Several clinical studies demonstrated its safety and efficacy in patients with both degenerative and functional MR. Based on these results, this catheter-based therapy received CE mark for both etiologies of MR in 2008, and approval from United States (US) Food and Drug Administration for degenerative MR with prohibited surgical risk in 2013. To date, around 12,000 patients underwent the MitraClip therapy worldwide. In the present review article, we describe the concept and procedural steps of the MitraClip therapy, results of major clinical trials, and current status in US. PMID- 25138941 TI - [Application of medical imaging to general thoracic surgery]. AB - Medical imaging technology is rapidly progressing. Positron emission tomography (PET) has played major role in the staging and choice of treatment modality in lung cancer patients. Magnetic resonance imaging (MRI) is now routinely used for mediastinal tumors and the use of diffusion-weighted images (DWI) may help in the diagnosis of malignancies including lung cancers. The benefits of medical imaging technology are not limited to diagnostics, and include simulation or navigation for complex lung resection and other procedures. Multidetector row computed tomography (MDCT) shortens imaging time to obtain detailed and precise volume data, which improves diagnosis of small-sized lung cancers. 3-dimensional reconstruction of the volume data allows the safe performance of thoracoscopic surgery. For lung lobectomy, identification of the branching structures, diameter, and length of the arteries is useful in selecting the procedure for blood vessel treatment. For lung segmentectomy, visualization of venous branches in the affected segments and intersegmental veins has facilitated the preoperative determination of the anatomical intersegmental plane. Therefore, the application of medical imaging technology is useful in general thoracic surgery. PMID- 25138942 TI - [Diagnostic bronchoscopy]. AB - Endoscopic technology has developed markedly with endobronchial ultrasonography (EBUS) having become dramatically widespread over the past 10 years. EBUS-guided transbronchial needle aspiration (EBUS-TBNA) has become an important modality for the mediastinal staging of lung cancer as well as mediastinoscopy. The combination of EBUS with a guide sheath( EBUS-GS) and virtual navigation systems, such as Bf-NAVI, LungPoint, superDimension/Bronchus system, is useful for diagnosis of small peripheral pulmonary lesions. Moreover, the ability to observe lesions has increased using picture enhancement developed by new methods such as autofluorescence imaging( AFI), narrow band imaging (NBI), and FUJI intelligent color enhancement( FICE). However, these modalities have limited value in detection of lung cancer and preneoplastic lesions. In recent years, the indications for AFI have widened and it can be now used for evaluation of tumor extension. Knowledge of these new technologies is certainly useful to allow their routine clinical use by respiratory surgeons. We will review these new technologies in this paper. PMID- 25138943 TI - [Present status of interventional pulmonology]. AB - Endobronchial intervention has been well established in therapeutic and palliative methods for patients with malignant and benign airway obstruction. Central airway tumor obstruction could lead to significant dyspnea or hemoptysis and dramatically lower the quality of life. Such symptoms can be relieved immediately via bronchoscopic intervention. Endobronchial therapies such as neodymium yttrium aluminum garnet( Nd:YAG) laser therapy, argon plasma coagulation and microwave coagulation or stent placement are well-established treatment options. Each of these modalities has its specific advantages and disadvantages. Laser therapy is direct thermal ablation applied to endobronchial tumors. It has sufficient power to vaporize tissues and produces an excellent coagulation effect. However, the risk of perforation is high. On the other hand, photodynamic therapy has the curative potential for patients with early superficial lung cancer using low power laser. Moreover, it has recently been approved for the treatment of other cancers including advanced lung cancer. Stent placement is an effective treatment to re-establish airway patency and immediately relieve the patient from life-threatening dyspnea. Stent restenosis, migration, mucus plug and hemoptysis are common short-term and longterm problems. It is important to select the appropriate treatment method for each patient to avoid complications and achieve successful results. PMID- 25138944 TI - [Thoracoscope for thoracoscopic surgery]. AB - Thoracoscope is very important in thoracoscopic surgery (TS). There are many types of telescope and monitor. Also the placement of access port and location of the monitor image often differ between each institutions. Thoracic surgeons need to know these features to perform good TS. In our department, 2,375 patients (98% of all operation) were underwent 3-ports TS for 5 years. Operator always stands by patient's right side and camera assistant stands by patient's left side. Using 2 monitors, left side of monitors image sets to patient's head side and camera assistant see the inverted image monitor. Regardless of the localization of the lesion, three ports are always placed in same intercostal space. One of the advantages of TS is the ability of obtaining close and magnified operative image which can be possible to be shared with assistant and other surgical staff. The other advantages is that surgeons can review the recorded surgical digital versatile disc(DVD). PMID- 25138945 TI - [Characteristics of customized device for video-assisted thoracoscopic surgery]. AB - Video-assisted thoracoscopic surgery (VATS) has been a mainstay in surgical interventions for an early staged lung cancer over a decade. VATS procedures are nowadays categorized into 2 groups. One is a modified open procedures through a mini-thoracotomy with customization of conventional instruments. The other is a port-access procedure with use of newly developed instruments for endoscopic surgery. The optimal device adapting for individual surgical manipulations should be selected to make a VATS procedure safer and more feasible. The sample extraction using a bag is a most important step when VATS is completed, because the rupture of bag can result in cancer cell contamination. More useful devices adapting either for mini-thoracotomy VATS or for port-access VATS, will be developed with advancement of medical technology. PMID- 25138946 TI - [Ultrasonically activated coagulating shears and the vessel sealing system in thoracic surgery]. AB - While the recent emergence of energy-based surgical techniques has made surgical procedures less invasive, the safety and proper usage have yet to be investigated. Here we review the experimental and clinical use of ultrasonically activated coagulating shears and a vessel sealing system in thoracic surgery. Both energy devices have been reported to be safe for use with the pulmonary artery and vein, with a burst pressure above 100 mmHg. Although their combined use with a ligature at a central site appeared to be adequate, the long-term durability has yet to be verified. The thoracic duct was reported to be sealed with sufficient burst pressure using these energy devices, which are expected to provide an alternative treatment for chylothorax. There have also been a few reports of their usage with the lung parenchyma, but their clinical adaptation is seemingly limited. PMID- 25138947 TI - [Efficacy of soft coagulation in thoracic surgery]. AB - The soft coagulation is a novel mode of electrosurgical device which automatically regulates its output voltage to stay below 190 Volts, causing pure coagulation without carbonization. The soft coagulation is available with bipolar and monopolar devices in thoracic surgery. Bipolar scissors can be applied for dissection of pulmonary vessels safely and efficiently without the damage to vessel wall. Monopolar soft coagulation can be applied to shrink bullous change of lung, cease air leakage from lung parenchyme or bleeding from pulmonary vessels. PMID- 25138948 TI - [Overview of surgical stapling devices]. AB - Surgical stapler allows surgeons to do simultaneous cut and suture quickly in excellent quality. Surgical stapler is currently used widely and has become indispensable tool for thoracic surgery, especially for endoscopic surgery such as thoracoscopic lung lobectomy, although there was some reluctance for use at the dawn of the era of mechanical stapling device. Devices should be used for right place in right manner. There are various kinds of stapling devices and surgeons should follow manufactures' instruction appropriately to avoid possible malfunctions of the devices. Surgeons must be aware of possible risks in use of stapling devices and must learn pitfalls. Stapling devices do and will continue to be evolved, and surgeons have to keep the know-how updated. PMID- 25138949 TI - [Operation-assisted robot.da Vinci (lung)]. AB - The most favorable advantage of robotic surgery is the markedly free movement of joint-equipped robotic forceps under 3-dimensional high-vision. Accurate operation makes complex procedures straightforward and may overcome weak points of previous thoracoscopic surgery. The efficiency and safety improves with acquiring skills. However, the spread of robotic surgery in the general thoracic surgery field has been delayed compared to those in other fields. The surgical indications include primary lung cancer, thymic diseases, and mediastinal tumors, but it is unclear whether technical advantages felt by operators are directly connected to merits for patients. Moreover, problems concerning the cost and education have not been solved. Although evidence is insufficient for robotic thoracic surgery, it may be an extension of thoracoscopic surgery, and reports showing its usefulness for primary lung cancer, myasthenia gravis, and thymoma have been accumulating. Now, important thing is to carry out clinical trial for advanced medical care and insurance acquisition. Although it is necessary to solve important problems such as safety, education, training, the cost for the future development, advancing robot technology has a possibility to markedly change general thoracic surgery. PMID- 25138950 TI - [Results of percutaneous cryoablation for malignant lung tumors compared with radiotherapy]. AB - Radiotherapy has been regularly applied mainly for inoperable patients with non- small cell lung cancer, and various clinical trials have been performed. On the other hand, we have applied percutaneous cryoablation for lung tumors (PCLT) since 2002. In this paper, we describe our experience of PCLT compared to the results of radiation treatment. Three-year local progression-free rates with stereotactic body radiotherapy were 79-92% in stage I A and 30-79% in stage I B. Those with proton radiotherapy were 82-89% in stage I A and 49-62% in stage I B. CTCAE grade >=3 complications occurred in 3-28% cases, such as radiation pneumonitis. As for PCLT, 1-, 2- and 3-year local progression-free rates were 80.4%, 69.0% and 67.7%, respectively. Pneumothorax, pleural effusion, and hemoptysis occurred after 61.7%, 70.5%, and 36.8% sessions, respectively. Of all cases with pneumothorax, 17.6% required chest tube insertion and 1.7% required pleurodesis. Delayed and recurrent pneumothorax occurred in 7.8% each. CTCAE grade >=3 complications occurred in 1.5% cases. The biggest advantage of PCLT compared with radiotherapy is the possibility to treat local recurrence at the same site as treated before. In addition, no radiation pneumonitis occurs in PCLT. Moreover, less space or budget is needed when PCLT is newly introduced in a hospital. Although high reliable clinical data is not achieved yet, PCLT is one of the promising methods in local treatment. PMID- 25138951 TI - [Sentinel node identification of lung cancer]. AB - Sentinel node identification is important for small-sized non small cell lung cancer patients who are candidates for segmentectomy in determining their eligibilities. Intraoperative sentinel node identification using indocyanine green or preoperative computed tomography lymphography by transbronchial injection of iopamidol are suitable for daily medical practices, because these methods take about only 10 minutes to identify sentinel nodes in addition to routine surgical or bronchoscopic procedures. PMID- 25138952 TI - [Infrared thoracoscopy]. AB - Infrared thoracoscopy with indocyanine green (ICG) is a new method of evaluating lung perfusion. We succeeded in visualizing lung emphysematous lesions and intersegmental borders using infrared thoracoscopy with ICG in animals, and within clinical investigations. There are 2 methods in infrared thoracoscopy. One is the 2-wavelength method, and the other is the 1-wavelength method. The 2- wavelength method is based on ICG absorption, and the 1-wavelength method is based on ICG fluorescence. The 2-wavelength method is superior for the clarity of images. On the other hand, the 1-wavelength method is superior for the duration of staining and the dose of ICG. Commonly, the inflation and deflation line has been used to identify the intersegmental border, but lung reinflation narrows the surgical view and can lead to prolongation of operation time, particularly in the context of video-assisted thoracic surgery (VATS). Infrared thoracoscopy with ICG is based on blood flow rather than on ventilation and can thus achieve anatomical segmentectomy without lung reinflation. This article closely reviews the principle and usefulness of infrared thoracoscopy, and difference between 2- and 1- wavelength method. PMID- 25138953 TI - [Image-enhanced endoscopy and magnifying endoscopy for esophageal cancer]. AB - Image diagnoses for esophageal cancer are progressing. With regard to endoscopic examination, chrome endoscopy using iodine have been performed so far to identify the range of lesion and to detect multiple primary cancers. In addition to that, endoscopic ultrasonography is used to diagnose the depth of tumor invasion and to identify lymph node metastasis. Recently, image-enhanced endoscopy (IEE) [e.g. Flexible spectral Imaging Color Enhancement (FICE), i-scan, Narrow Band Imaging (NBI), Autofluorescence imaging (AFI)] has developed. IEE is useful to detect superficial lesion, and is being utilized for diagnosing the tumor depth of invasion by using magnifying endoscopy( ME) together. In this literature, recent progress of endoscopic diagnosis, especially about IEE and ME, is reviewed. In addition to that, a way of endoscopic examination using IEE and ME is introduced. PMID- 25138954 TI - [Indocyanine green injection method for evaluating blood flow of gastric tube on esophageal cancer surgery]. AB - The blood flow of esophageal substitute has been subjectively evaluated by surgeons. HyperEye Medical System (HEMS) allows for the visualization of the fluorescent image of indocyanine green (ICG) enhanced by near-infrared light among the surrounding vivid color images. We applied HEMS for evaluating the blood flow of right gastroepiploic artery and tissue blood flow of whole gastric tube during operation. Quantification of arterial blood flow and venous return has also been now developing for objective evaluation. We hope HEMS contributes to development of surgical results on various fields by establishing quantification of blood flow and clinical application. PMID- 25138955 TI - [Thoracoscopic esophagectomy]. AB - In recent years, the number of facilities performing thoracoscopic surgery of the esophagus has increased. Thoracoscopic surgery has many advantages, such as a magnification effect, good lighting, and a wide field of view. Esophagectomy requires fine manipulation within a deep and narrow space. Thus, thoracoscopic surgery is suitable for the performance of esophagectomy. The body position during this procedure may be either prone or left lateral decubitus. Because there are advantages in both cases, the relative merits are controversial. The operation time is longer than that of open thoracotomy, but the amount of bleeding is small in most cases of thoracoscopic esophagectomy. There are also some reports that thoracoscopic esophagectomy is comparable with open esophagectomy in terms of radicality and quality of lymph node dissection, and the intensive care unit and hospital stay durations are shortened. Robot-assisted esophagectomy is a promising technology for the fine manipulations and high quality 3-dimensional visualization required in the performance of esophageal thoracoscopic surgery. Thoracoscopic esophagectomy will become more widespread and undergo further development in the future with the spread of robotic surgery and 3-dimensional endoscopic surgery. PMID- 25138956 TI - Compressed-sensing-based fluorescence molecular tomographic image reconstruction with grouped sources. AB - BACKGROUND: Although the quality of reconstructed results can be improved with the increment of the number of measurements, the scale of the matrices involved in the reconstruction of fluorescence molecular tomography (FMT) will become larger, which leads to the poor efficiency of the process of tomographic image reconstruction. In this paper, we proposed a new method for image reconstruction of FMT based on compressed sensing, in which a scheme of grouped sources is incorporated. METHODS: The forward equations are implemented using the finite element method (FEM). The reconstruction model is formulated under the framework of compressed sensing theory. The regularization term and the total variation penalty are incorporated in the objective function. During the reconstruction of FMT, the sources are divided into two groups for iteration in turn. One group of sources is employed in the first iteration of inverse problem, and the other group is employed in the next iteration. RESULTS: Simulation results demonstrate that the computation time and mean square error (MSE) of the reconstruction with our algorithm are less than those with the traditional method. The proposed algorithm can reconstruct the target with enhanced contrast and more accurate shape. CONCLUSIONS: The proposed algorithm can significantly improve the speed and accuracy of the reconstruction of FMT. Furthermore, our compressed-sensing based method can reduce the number of measurements. PMID- 25138958 TI - The beta-adrenoceptor agonist isoproterenol rescues acetaminophen-injured livers: Is it really safe? PMID- 25138959 TI - How Australian and New Zealand schools of optometry prepare students for culturally competent practice. AB - BACKGROUND: This study is an investigation of how Australian and New Zealand schools of optometry prepare students for culturally competent practice. The aims are: (1) to review how optometric courses and educators teach and prepare their students to work with culturally diverse patients; and (2) to determine the demographic characteristics of current optometric students and obtain their views on cultural diversity. METHODS: All Australian and New Zealand schools of optometry were invited to participate in the study. Data were collected with two surveys: a curriculum survey about the content of the optometric courses in relation to cultural competency issues and a survey for second year optometry students containing questions in relation to cultural awareness, cultural sensitivity and attitudes to cultural diversity. RESULTS: Four schools of optometry participated in the curriculum survey (Deakin University, Flinders University, University of Melbourne and University of New South Wales). Sixty three students (22.3 per cent) from these four schools as well as the University of Auckland participated in the student survey. Cultural competency training was reported to be included in the curriculum of some schools, to varying degrees in terms of structure, content, teaching method and hours of teaching. Among second year optometry students across Australia and New Zealand, training in cultural diversity issues was the strongest predictor of cultural awareness and sensitivity after adjusting for school, age, gender, country of birth and language other than English. CONCLUSION: This study provides some evidence that previous cultural competency-related training is associated with better cultural awareness and sensitivity among optometric students. The variable approaches to cultural competency training reported by the schools of optometry participating in the study suggest that there may be opportunity for further development in all schools to consider best practice training in cultural competency. PMID- 25138960 TI - Response to impact of obstructive sleep apnea on cardiovascular outcomes in patients treated with percutaneous coronary intervention: rationale and design of the sleep and stent study. PMID- 25138961 TI - Low-resolution structures of OmpA?DDM protein-detergent complexes. AB - We have used SAXS to determine the low-resolution structure of the outer-membrane protein OmpA from E. coli solubilized by the surfactant dodecyl maltoside (DDM). We have studied three variants of the transmembrane domain of OmpA-namely monomers, self-associated dimers, and covalently linked dimers-as well as the monomeric species of the full-length protein with the periplasmic domain. We can successfully model the structures of the monomeric and covalently linked dimer as one and two natively folded proteins in a DDM micelle, respectively, whereas the noncovalently linked dimer presents a more complicated structure, possibly due to higher-order species. We have determined the structure of the full-length protein to be that of a globular periplasmic domain attached through a flexible linker to the transmembrane domain. This approach provides valuable information about how membrane proteins are embedded in amphiphilic environments. PMID- 25138962 TI - Maximizing binding capacity for protein A chromatography. AB - Advances in cell culture expression levels in the last two decades have resulted in monoclonal antibody titers of >=10 g/L to be purified downstream. A high capacity capture step is crucial to prevent purification from being the bottleneck in the manufacturing process. Despite its high cost and other disadvantages, Protein A chromatography still remains the optimal choice for antibody capture due to the excellent selectivity provided by this step. A dual flow loading strategy was used in conjunction with a new generation high capacity Protein A resin to maximize binding capacity without significantly increasing processing time. Optimum conditions were established using a simple empirical Design of Experiment (DOE) based model and verified with a wide panel of antibodies. Dynamic binding capacities of >65 g/L could be achieved under these new conditions, significantly higher by more than one and half times the values that have been typically achieved with Protein A in the past. Furthermore, comparable process performance and product quality was demonstrated for the Protein A step at the increased loading. PMID- 25138964 TI - Graves' dermopathy and acropachy. PMID- 25138963 TI - Adipogenic changes of hepatocytes in a high-fat diet-induced fatty liver mice model and non-alcoholic fatty liver disease patients. AB - Non-alcoholic fatty liver disease (NAFLD) is characterized by steatosis associated with liver inflammation. As NAFLD progresses, triglycerides increase within hepatocytes, causing typical vacuoles that resemble adipocytes. However, whether these morphological changes in hepatocytes indicate potential functional changes is unclear. C57BL/6J mice were fed a high-fat diet (HFD) containing 42% fat. Markers for adipocytes in the liver were measured using real-time PCR, Western blot, and double immunofluorescent labeling. Cytokines in cell culture supernatants were quantified with ELISA. To determine the macrophage phenotype, hepatic classical M1 markers and alternative M2 markers were analyzed. After a 24 week feeding period, adipocyte markers aP2 and PPARgamma increased at both the mRNA and protein level in the liver of HFD-fed mice. FITC-labeled aP2 and rhodamine-labeled albumin were both stained in the cytoplasm of steatotic hepatocytes as observed under confocal laser scanning microscopy. Cell membrane bound E-cadherin and albumin expression were reduced in steatotic hepatocytes compared to controls. However, hepatic adiponectin and adiponectin receptor-2 expression decreased with upregulation of hepatic CD36, suggesting impaired adiponectin activity in livers of HFD-fed mice. Moreover, steatotic primary hepatocytes not only released pro-inflammatory cytokines such as TNFalpha, MCP-1, IL-6, and IL-18, but also could activate macrophages when co-cultured in vitro. In vivo, hepatic expression of M1 genes such as iNOS and TNFalpha was markedly increased in HFD-fed mice. In contrast, hepatic expression of M2 genes such as Arg1 and CD206 was significantly reduced. Specifically, the ratio of TNFalpha to CD206 in HFD-fed mice was notably upregulated. Overexpression of adipocyte specific genes in hepatocytes and their secretory function and epithelial phenotype impairment in NAFLD cause functional changes in steatotic hepatocytes aside from morphological changes. This suggests that adipogenic changes in hepatocytes are involved in pathogenesis of NAFLD. PMID- 25138965 TI - Water-mediated interactions between trimethylamine-N-oxide and urea. AB - The amphiphilic osmolyte trimethylamine-N-oxide (TMAO) is commonly found in natural organisms, where it counteracts biochemical stress associated with urea in aqueous environments. Despite the important role of TMAO as osmoprotectant, the mechanism behind TMAO's action has remained elusive. Here, we study the interaction between urea, TMAO, and water in solution using broadband (100 MHz 1.6 THz) dielectric spectroscopy. We find that the previously reported tight hydrogen bonds between 3 water molecules and the hydrophilic amine oxide group of TMAO, remain intact at all investigated concentrations of urea, showing that no significant hydrogen bonding occurs between the two co-solutes. Despite the absence of direct TMAO-urea interactions, the solute reorientation times of urea and TMAO show an anomalous nonlinear increase with concentration, for ternary mixtures containing equal amounts of TMAO and urea. The nonlinear increase of the reorientation correlates with changes in the viscosity, showing that the combination of TMAO and urea cooperatively enhances the hydrogen-bond structure of the ternary solutions. This nonlinear increase is indicative of water mediated interaction between the two solutes and is not observed if urea is combined with other amphiphilic solutes. PMID- 25138967 TI - Influence of fluorescent dye on physical-mechanical properties of luting cements for confocal microscopy analysis. AB - AIMS: To evaluate the influence of a fluorescent dye (rhodamine B) on the physical and mechanical properties of three different luting cements: a conventional adhesive luting cement (RelyX ARC, 3M/ESPE), a self-adhesive luting cement (RelyX U-200, 3M/ESPE), and a self-etching and self-adhesive luting cement (SeT PP, SDI). MATERIALS AND METHODS: The cements were mixed with 0.03 wt% rhodamine B, formed into bar-shaped specimens (n = 10), and light cured using an LED curing unit (Radii, SDI) with a radiant exposure of 32 J/cm(2) . The Knoop hardness (KHN), flexural strength (FS), and Young's modulus (YM) analyses were evaluated after storage for 24 h. RESULTS: Outcomes were subjected to two-way ANOVA and Tukey's test (P = 0.05) for multiple comparisons. No significant differences in FS or YM were observed among the tested groups (P >= 0.05); the addition of rhodamine B increased the hardness of the luting cements tested. CONCLUSION: The addition of a fluorescent agent at 0.03 wt% concentration does not negatively affect the physical-mechanical properties of the luting cement polymerization behavior. PMID- 25138966 TI - Oxygen uptake at different intensities and sub-techniques predicts sprint performance in elite male cross-country skiers. AB - PURPOSE: To investigate the relationship between sprint-prologue performance (using the classical technique) and the oxygen uptake at the lactate threshold (VO2obla), maximal oxygen uptake (VO2max), and mean oxygen uptake during double poling (VO2dp). METHODS: Eight elite male cross-country skiers [age 24.8 +/- 4.8 years, (mean +/- SD)] completed two treadmill roller-skiing tests using the diagonal-stride technique and a 60 s double-poling test on a ski-ergometer to determine their VO2obla, VO2max, and VO2dp. Performance data were generated from a 1.25 km sprint prologue. Power-function modelling was used to predict the skiers' race speeds based on the oxygen-uptake variables and body mass. RESULTS: There were correlations between the race speed and the absolute expression of the VO2obla (r = 0.79, P = 0.021), VO2max (r = 0.86, P = 0.0069), and VO2dp (r = 0.94, P = 0.00062). The following power-function models were established for race speed prediction: 1.09 . VO2obla(0.21), 1.05 . VO2max(0.21), and 1.19 . VO2dp(0.20); these models explained 60% (P = 0.024), 73% (P = 0.0073), and 87% (P = 0.00073), respectively, of the variance in the race speed. However, body mass did not contribute to any of the models (P = 0.97, 0.88, and 0.21, respectively). CONCLUSIONS: Oxygen uptake at different intensities and sub-techniques is an indicator of elite male sprint-prologue performance. The absolute expression of the investigated oxygen-uptake variables should be used when evaluating elite male sprint-prologue performances; if skiers oxygen uptake differs by 1%, their performances will likely differ by 0.2% in favour of the skier with higher oxygen uptake. PMID- 25138968 TI - Treatment of Complicated Spontaneous Twin Anemia-Polycythemia Sequence via Fetoscopic Laser Ablation of the Vascular Communications. AB - Monochorionic diamniotic twins share a single placenta and have intertwin vascular communications that link the circulatory systems of the twins together. Twin anemia-polycythemia sequence (TAPS) is an atypical form of twin-twin transfusion syndrome (TTTS) caused by net transfer of blood from one fetus to the other and is characterized by large intertwin hemoglobin differences in the absence of oligohydramnios and polyhydramnios. This condition may develop spontaneously (sTAPS) or as a result of residual vascular communications after prior laser surgery. Because of the relatively low prevalence and lack of clinical awareness, the natural history of sTAPS is unclear and the antenatal treatment remains controversial. Case series of sTAPS have described expectant management with timed delivery, intrauterine blood transfusion, and fetoscopic laser treatment. Favorable outcomes have been described in cases of uncomplicated sTAPS that underwent conservative measures. However, we believe that there may be a subgroup of high-risk or complicated sTAPS patients that may benefit from definitive treatment afforded by fetoscopic laser therapy. We describe 3 complicated cases of sTAPS successfully treated with selective laser photocoagulation of communicating vessels. In 2 of the cases, placental pathology identified thrombosed fetal vessels of the polycythemic twin. PMID- 25138970 TI - West Nile virus lineage 2 isolated from Culex modestus mosquitoes in the Czech Republic, 2013: expansion of the European WNV endemic area to the North? AB - We report the detection and isolation of four almost identical strains of West Nile virus (WNV) lineage 2from Culex modestus mosquitoes collected at three fish ponds in South Moravia, Czech Republic, during August 2013. Phylogenetic analysis demonstrated that the Czech WNV strains isolated are closely related to Austrian, Italian and Serbian strains reported in 2008,2011 and 2012, respectively. Our findings show the current northernmost range of lineage 2 WNV in Europe. PMID- 25138969 TI - Coupling of sterically hindered trisubstituted olefins and benzocyclobutenones by C-C activation: total synthesis and structural revision of cycloinumakiol. AB - The first total syntheses of the proposed structure of cycloinumakiol (1) and its C5 epimer (18) are achieved in a concise and efficient fashion. Starting from the known 3-hydroxybenzocyclobutenone, 1 and 18 are obtained in nine and five steps with overall yields of 15% and 33%, respectively. The key for the success of this approach is the use of a catalytic C-C activation strategy for constructing the tetracyclic core of 1 through carboacylation of a sterically hindered trisubstituted olefin with benzocyclobutenone. In addition, the structure of the natural cycloinumakiol was reassigned to 19-hydroxytotarol (7) through X-ray diffraction analysis. This work demonstrates the potential of C-C activation for streamlining complex natural product synthesis. PMID- 25138971 TI - A multi-country outbreak of Salmonella Newport gastroenteritis in Europe associated with watermelon from Brazil, confirmed by whole genome sequencing: October 2011 to January 2012. AB - In November 2011, the presence of Salmonella Newport in a ready-to-eat watermelon slice was confirmed as part of a local food survey in England. In late December 2011, cases of S. Newport were reported in England, Wales, Northern Ireland, Scotland, Ireland and Germany. During the outbreak, 63 confirmed cases of S. Newport were reported across all six countries with isolates indistinguishable by pulsed-field gel electrophoresis from the watermelon isolate.A subset of outbreak isolates were whole-genome sequenced and were identical to, or one single nucleotide polymorphism different from the watermelon isolate.In total, 46 confirmed cases were interviewed of which 27 reported watermelon consumption. Further investigations confirmed the outbreak was linked to the consumption of watermelon imported from Brazil.Although numerous Salmonella outbreaks associated with melons have been reported in the United States and elsewhere, this is the first of its kind in Europe.Expansion of the melon import market from Brazil represents a potential threat for future outbreaks. Whole genome sequencing is rapidly becoming more accessible and can provide a compelling level of evidence of linkage between human cases and sources of infection,to support public health interventions in global food markets. PMID- 25138972 TI - Epidemiology and outcome of invasive pneumococcal disease among adults in Belgium, 2009-2011. AB - This epidemiological study examined morbidity and case fatality of invasive pneumococcal disease (IPD) in adults in Belgium as well as distribution and antibiotic susceptibility of Streptococcus pneumoniae serotypes.Adults hospitalised with microbiologically proven IPD were prospectively enrolled. The study started in 2009 with patients aged >=50 years, whereas in 2010 and 2011, patients aged >=18 years were included. The clinical presentation, patient profile, treatment, outcome, and mortality were recorded during hospitalisation.Outcome was also assessed one month afterdischarge. Of the 1,875 patients with IPD identified, 1,332 were included in the analysis. Bacteraemic pneumonia, affecting 1,049 of the patients, was the most frequent IPD type (79%), and chronic obstructive pulmonary disease and cancer were the main comorbidities.One-third of patients required admission to intensive care unit. A total of 208 (16%) patients died during hospitalisation and an additional 21 (2%) within one month after discharge. Case fatality rates of >=20%were observed in patients with chronic heart failure, hepatic disease, and renal insufficiency. Serotypes 7F, 1, 19A, and 3 were the most prevalent and together accounted for 47% (569/1,214) of all IPD cases and 42% (80/189) of mortality. Of the patient isolates, 21% (255/1,204) were resistant to erythromycin and 22% (264/1,204) to tetracycline. Penicillin non-susceptibility was mostly found in serotype 19A isolates. These baseline data are essential when assessing the impact of pneumococcal conjugate vaccination in adults in the future. PMID- 25138973 TI - Information resources and latest news about Ebola virus disease available from ECDC. PMID- 25138974 TI - European Commission launches consultation on Science 2.0. PMID- 25138977 TI - IL-17 and IL-22 serum levels in greenhouse workers exposed to pesticides. AB - INTRODUCTION: Altered immune function may be an indicator of increased potential for the development of immunologically based diseases such as cancer, hypersensitivity and autoimmunity. MATERIALS AND METHODS: To investigate whether Th17 and Th22 cells are targeted by pesticide exposure, we analyzed IL-17 and IL 22 serum levels in a population of 64 greenhouse workers. RESULTS AND CONCLUSION: A significant increase in IL-22 concentration was observed in serum of the exposed subjects compared to controls. These findings support the hypothesis that exposure to pesticides may reduce host defenses against infections and cancer. PMID- 25138978 TI - Operating characteristics of PROMIS four-item depression and anxiety scales in primary care patients with chronic pain. AB - OBJECTIVE: Depression and anxiety are prevalent in patients with chronic pain and adversely affect pain, quality of life, and treatment response. The purpose of this psychometric study was to determine the reliability and validity of the four item Patient Reported Outcomes Measurement Information System (PROMIS) depression and anxiety scales in patients with chronic pain. DESIGN: Secondary analysis of data from the Stepped Care to Optimize Pain care Effectiveness study, a randomized clinical trial of optimized analgesic therapy. SETTING: Five primary care clinics at the Roudebush VA Medical Center (RVAMC) in Indianapolis, Indiana. SUBJECTS: Two hundred forty-four primary care patients with chronic musculoskeletal pain. METHODS: All patients completed the four-item depression and anxiety scales from the PROMIS 29-item profile, as well as several other validated psychological measures. The minimally important difference (MID) using the standard error of measurement (SEM) was calculated for each scale, and convergent validity was assessed by interscale correlations at baseline and 3 months. Operating characteristics of the PROMIS measures for detecting patients who had probable major depression or were anxiety-disorder screen-positive were calculated. RESULTS: The PROMIS scales had good internal reliability, and the MID (as represented by two SEMs) was 2 points for the depression scale and 2.5 points for the anxiety scale. Convergent validity was supported by strong interscale correlations. The optimal screening cutpoint on the 4- to 20-point PROMIS scales appeared to be 8 for both the depression and anxiety scales. CONCLUSIONS: The PROMIS four-item depression and anxiety scales are reasonable options as ultra brief measures for screening in patients with chronic pain. PMID- 25138979 TI - Early-onset Alzheimer's disease in two Iranian families: a genetic study. AB - BACKGROUND: Early-onset Alzheimer's disease (EOAD) represents less than 5% of all AD cases. Autosomal dominant EOAD has been defined as the occurrence of at least three cases in three generations. Mutations in the amyloid precursor protein (APP), presenilin-1 and presenilin-2 genes have been recognized to be the cause of EOAD. OBJECTIVE: We investigated the genotype of EOAD in two generations of two families with EOAD living in an Iranian village. METHODS: The polymerase chain reaction method was used to study the presenilin-1 and APP genes in 25 subjects of these generations. RESULTS: A guanine-to-adenine transition in exon 17 of the APP gene resulting in a valine-to-isoleucine substitution at codon 717 was detected in 14 subjects including 6 patients with EOAD. CONCLUSION: This mutation demonstrates the importance of gamma-secretase, the necessity of early detection of patients with memory decline in the susceptible population and raising public awareness of consanguinity marriages. PMID- 25138980 TI - Surgical versus conservative treatment for high-risk stress fractures of the lower leg (anterior tibial cortex, navicular and fifth metatarsal base): a systematic review. AB - AIM: To compare surgical and conservative treatment for high-risk stress fractures of the anterior tibial cortex, navicular and proximal fifth metatarsal. METHODS: Systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, SPORTDiscus and PEDro were performed to identify relevant prospective and retrospective studies. Two reviewers independently extracted data and assessed methodological quality. Main outcomes were return to sport and complication rate. RESULTS: 18 studies were included (2 anterior tibia (N=31), 8 navicular (N=200) and 8 fifth metatarsal (N=246)). For anterior tibial fracture, no studies on initial surgery were eligible. Conservative treatment resulted in high complication rates and few cases returned to sport. For navicular fracture, a weighted mean return to sport of 22 for conservative and 16 weeks for surgical treatment was found. Six weeks of non-weightbearing cast was mostly used as conservative treatment. Surgical procedures varied widely. For the fifth metatarsal fracture, weighted mean return to sport was 19 for conservative and 14 weeks for surgical treatment. Surgery consisted of intramedullary screw fixation or tension band wiring. For conservative methods, insufficient details were reported. Overall, there was a high risk of bias; sample sizes were small and GRADE level of evidence was low. CONCLUSIONS: Strong conclusions for surgical or conservative therapy for these high-risk stress fractures cannot be drawn; quality of evidence is low and subjected to a high risk of bias. However, there are unsatisfying outcomes of conservative therapy in the anterior tibia. The role of initial surgery is unknown. For the navicular, surgery provided an earlier return to sport; and when treated conservatively, weightbearing should be avoided. For the fifth metatarsal, surgery provided the best results. Treatment decision-making would greatly benefit from further prospective research. STUDY REGISTRATION NUMBER: PROSPERO database of systematic reviews: CRD42013004201. PMID- 25138982 TI - Cancer Knowledge and Opportunities for Education Among HIV-Infected Patients in an Urban Academic Medical Center. AB - HIV-infected patients frequently present with advanced stage cancer. It is possible that late stage presentation may be related to lack of cancer knowledge and/or barriers to care. Questionnaires were administered to 285 adult HIV infected patients to evaluate knowledge of cancer risk factors and symptoms and barriers to care between 2011 and 2012. Differences in mean and percent scores by group were assessed using a t test for independent samples and chi-square analysis, respectively. Respondents were predominantly male (64%), African American (86%), and low income (60% < $10,000/year). Thirty-four (12%) had been diagnosed with cancer, and 169 (59%) had a family history of cancer. The mean knowledge score was 17.5 out of 24 questions (73%). Mean scores were not significantly different by sex, age, race, or income. Respondents with a college education scored significantly higher than those with less than a high school education (p < 0.01). In unadjusted analysis, a higher proportion of patients with a personal/family history of cancer (74%) scored in the highest quartile (>70% correct) compared to those without any personal history of cancer (62%) (p = 0.03). There was a higher level of cancer knowledge in this population compared to studies that have evaluated the HIV-uninfected population. Nevertheless, there were knowledge deficits, suggesting the need for further education about cancer to improve earlier detection rates and, ultimately, outcomes. PMID- 25138984 TI - Molecular interactions driving the layer-by-layer assembly of multilayers. PMID- 25138983 TI - Older women's experience with a benign breast biopsy-a mixed methods study. AB - BACKGROUND: Little is known about older women's experience with a benign breast biopsy. OBJECTIVES: To examine the psychological impact and experience of women >= 65 years of age with a benign breast biopsy. DESIGN: Prospective cohort study using quantitative and qualitative methods. SETTING: Three Boston-based breast imaging centers. PARTICIPANTS: Ninety-four English-speaking women >= 65 years without dementia referred for breast biopsy as a result of an abnormal mammogram, not aware of their biopsy results at baseline, and with a subsequent negative biopsy. MEASUREMENTS: We interviewed women at the time of breast biopsy (before women knew their results) and 6 months post-biopsy. At both interviews, participants completed the validated negative psychological consequences of screening mammography questionnaire (PCQ, scores range from 0 to 36 [high distress], PCQ >= 1 suggests a psychological consequence, PCQs <1 are reported at time of screening) and women responded to open-ended questions about their experience. At follow-up, participants described the quality of information received after their benign breast biopsy. We used a linear mixed effects model to examine if PCQs declined over time. We also reviewed participants' open-ended comments for themes. RESULTS: Overall, 88% (83/94) of participants were non Hispanic white and 33% (31/94) had a high-school degree or less. At biopsy, 76% (71/94) reported negative psychological consequences from their biopsy compared to 39% (37/94) at follow-up (p < 0.01). In open-ended comments, participants noted the anxiety (29%, 27/94) and discomfort (28%, 26/94) experienced at biopsy (especially from positioning on the biopsy table). Participants requested more information to prepare for a biopsy and to interpret their negative results. Forty-four percent (39/89) reported at least a little anxiety about future mammograms. CONCLUSIONS: The high psychological burden of a benign breast biopsy among older women significantly diminishes with time but does not completely resolve. To reduce this burden, older women need more information about undergoing a breast biopsy. PMID- 25138986 TI - The impact of intolerance of uncertainty, worry and irritability on quality of life in persons with epilepsy: irritability as mediator. AB - Epilepsy is a neurological disorder afflicting many people in the world. The impact of epilepsy on the quality of life of those afflicted with epilepsy is greater than the limitations imposed by the seizures alone. Among the several psychological disorders found to be comorbid with epilepsy are anxiety and depression, both of which impair quality of life in epilepsy. Some studies have reported that the anxiety seen in epilepsy is characterized by worry while the depression seen is characterized by irritability. A concept common to both anxiety and depression is intolerance of uncertainty. Therefore, the study explores the relationship between intolerance of uncertainty, worry and irritability and their association to quality of life in epilepsy. A descriptive correlational research method was used and the research sample comprised 60 consecutive referrals seeking outpatient neurological services for epilepsy at Alavi Hospital in Ardebil. Data were collected by administering the Penn State Worry Questionnaire, Intolerance of Uncertainty Scale, Irritability Questionnaire and Quality of Life in Epilepsy Inventory. Data were analyzed using Pearson's correlation coefficients and multivariate regression analysis. Mediation and moderation analyses were conducted. Findings indicated that intolerance of uncertainty, worry and irritability have unique significant effects on quality of life. The implications are that interventions aimed at improving the quality of life of patients with epilepsy should address their feelings of uncertainty, worry and irritability. Furthermore, irritability seems to mediate the impact of both intolerance of uncertainty and worry on quality of life of individuals with epilepsy. No significant moderation effects were noted. Results underscore the important role of irritability in the quality of life of persons with epilepsy. The findings are discussed with reference to the possibility of particular predisposing temperaments and add credence to the suggestion of an epileptic personality. PMID- 25138985 TI - Serum levels of M-CSF, RANKL and OPG in rats fed with Kashin-Beck disease affected diet. AB - OBJECTIVE: There were no studies on the macrophage colony-stimulating factor (M CSF), receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in the pathogenesis of Kashin-Beck disease (KBD). The objective of the present study was to investigate the serum M-CSF, RANKL and OPG in rats fed with KBD-affected diet. METHODS: Ninety Wistar rats were divided into five groups. The rats received standard commercial feed with or without T-2 toxin additive, low protein feed with or without or T-2 toxin additive and the KBD-affected feed. The serum bioactivity of M-CSF, RANKL and OPG was tested by enzyme-linked immunosorbent assay. RESULTS: The serum levels of M-CSF in E group rats were higher than those in the other groups in the five groups (P < 0.01). The serum levels of RANKL and OPG in E group rats were highest in the five groups and have significant difference compared to the other groups (P < 0.05). CONCLUSIONS: The molecule of M-CSF, RANKL and OPG may be involved in the regulation of epiphyseal plate injury and repair in KBD, and its participation in the pathogenesis of KBD should be studied in the future. PMID- 25138987 TI - Calcification of the internal pudendal artery and development of erectile dysfunction in adenine-induced chronic kidney disease: a sentinel of systemic vascular changes. AB - INTRODUCTION: Chronic kidney disease (CKD), erectile dysfunction (ED), and cardiovascular disease share common vascular etiologies and risk factors. AIM: Using a rat model, this is the first study to characterize the consequences of CKD in the onset and development of ED associated with differential regional vascular calcification and circulatory changes. METHODS: Stable CKD was generated at 3 weeks in male Sprague-Dawley rats given dietary adenine and progressed until 7 weeks. Mineral content and morphometry were assessed in the internal pudendal arteries (IPAs), thoracic aorta, and carotid artery. Endothelial function was determined via changes in serum von Willebrand factor (VWF) and endothelium dependent relaxation of the thoracic aorta. RESULTS: In severe CKD rats, calcium and phosphate content in all arteries increased, and pulse wave velocity was elevated. Distal IPA segments, in particular, were the first to calcify, but penile tissue per se did not. CKD rats had endothelial dysfunction, as indicated by a decrease in acetylcholine-mediated relaxation (~40%) and an increase in serum VWF (~40%), as well as increased lumen diameter (20%) of the distal IPA. Erectile function, assessed using a centrally acting dopaminergic agent, was significantly impaired by 7 weeks (~40%). CONCLUSIONS: In CKD, the distal IPA appears to be more susceptible to vascular dysfunction and calcification. Additionally, the onset of ED may be an important sentinel of impending systemic vascular disease. To confirm this concept, future experimental and clinical studies will need to examine a range of vessel types and the use of supplementary methods to assess erectile function. PMID- 25138988 TI - Treatment effects of a fixed intermaxillary device to correct class II malocclusions in growing patients. AB - BACKGROUND: The objective of this study was to evaluate the treatment effects of ForsusTM Fatigue Resistant Device (FRD; 3M Unitek, Monrovia, CA, USA) in growing patients with Class II non-extraction malocclusions. METHODS: A retrospective sample of 24 class II patients treated consecutively with the FRD followed by comprehensive orthodontic treatment was compared to a sample of untreated control subjects from the Bolton Brush Study who was matched in age, sex, and craniofacial morphology. Lateral cephalometric radiographs were taken before treatment (T1) and after removal of fixed appliances (T2). Growth changes were subtracted from the treatment changes to obtain the treatment effects of the appliance. Data were analyzed using ANOVA and a match paired t test. RESULTS: Significant differences were found between the treated and control groups for 12 of the 29 measured variables (Co-Gn minus Co-Apt, Wits, Is-OLp, Ii-OLp, overjet, Mi-OLp, molar relationship, overbite, Mic-ML, SNA, ANB, and Ii-ML). With 27.8 months of treatment, all patients were corrected to a class I dental arch relationship. Overjet and molar relationships were improved by an average of 4.7 and 3.1 mm, respectively. This was contributed by a 1.2 mm of restraint in forward maxillary growth, 0.7 mm of forward movement of the mandible, 1.5 mm of backward movement of the maxillary incisors, 1.3 mm forward movement of the mandibular incisors, 0.5 mm backward movement of the maxillary molars, and 1.3 mm of forward movement of the mandibular molars. The overbite was decreased by 2 mm with no significant change in the occlusal, palatal, or mandibular plane. Individual variations in response to the FRD treatment were large for most of the parameters tested. Significant differences in treatment changes between male and female subjects were found only in a few parameters measured. CONCLUSIONS: These results demonstrate that significant overjet and overbite corrections can be obtained with the Forsus FRD in conjunction with comprehensive orthodontic treatment. PMID- 25138989 TI - Hyperplasia of rib and vertebra, associated with infiltrating lipoma: a rare case of focal overgrowth. AB - PURPOSE: Syndromes with focal overgrowth are rare and diagnosis is difficult because manifestations are highly variable and symptoms overlap between syndromes. Diagnosis depends on clinical history, physical examination, and radiologic and histologic findings. This report describes a case of focal overgrowth of the left seventh rib and half of the adjacent thoracic vertebra, with overlying infiltrating lipoma. METHODS: A 13-year-old boy presented with an asymptomatic chest wall mass caused by enlargement of the seventh rib and an overlying soft-tissue mass accompanied by enlargement of half of the seventh thoracic vertebra. MRI showed infiltration of lipomatous tissue in the muscles, but no interfascicular accumulation of adipose tissue in the thoracic spinal nerve. RESULTS: A similar case was presented in 1985 but without MR imaging. CONCLUSION: We report on a second case of focal overgrowth of a rib and half of the adjacent vertebra, and overlying lipoma. In addition to the first case, we present MR images demonstrating infiltration of the adipose tissue. PMID- 25138990 TI - PlasmaKineticTM versus cold knife internal urethrotomy in terms of recurrence rates: a prospective randomized study. AB - OBJECTIVE: To evaluate the efficacy and outcomes of PlasmaKineticTM urethrotomy against cold knife direct vision internal urethrotomy in terms of recurrence rates. PATIENTS AND METHODS: A total of 136 male patients with urethral strictures were enrolled into the study. The patients were allocated to cold knife or PlasmaKinetic urethrotomy groups sequentially by using computer generated numbers. Group A (PlasmaKinetic) and group B (cold knife) included 70 and 66 patients, respectively. All patients were reevaluated at the 3rd, 9th and 18th month postoperatively with uroflowmetry. RESULTS: Group A patients had a postoperative 3rd-month maximum flow rate value of 16.09 ml/s, whereas this same parameter was 15.15 ml/s in group B (p < 0.05). The urethral stricture recurrence rate up to the 9-month period was statistically significant for group A (14%) compared with group B (30%). When we compared the recurrence rates of these groups from postoperative day 1 up to the 18th month, the results were 37% for group A and 33% for group B (p > 0.05). CONCLUSION: PlasmaKinetic urethrotomy provides a better recurrence-free rate during the early period compared with conventional cold knife therapy. Nevertheless, the outcome of the stricture did not change and fibrotic tissue reformed between the 9th and the 18th month. PMID- 25138991 TI - Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody. AB - INTRODUCTION: Biologic drugs are large molecules that do not cross the blood- brain barrier (BBB). Brain penetration is possible following the re-engineering of the biologic drug as an IgG fusion protein. The IgG domain is a MAb against an endogenous BBB receptor such as the transferrin receptor (TfR). The TfRMAb acts as a molecular Trojan horse to ferry the fused biologic drug into the brain via receptor-mediated transport on the endogenous BBB TfR. AREAS COVERED: This review discusses TfR isoforms, models of BBB transport of transferrin and TfRMAbs, and the genetic engineering of TfRMAb fusion proteins, including BBB penetrating IgG neurotrophins, IgG-decoy receptors, IgG-lysosomal enzyme therapeutics and IgG avidin fusion proteins, as well as BBB transport of bispecific antibodies formed by fusion of a therapeutic antibody to a TfRMAb targeting antibody. Also discussed are quantitative aspects of the plasma pharmacokinetics and brain uptake of TfRMAb fusion proteins, as compared to the brain uptake of small molecules, and therapeutic applications of TfRMAb fusion proteins in mouse models of neural disease, including Parkinson's disease, stroke, Alzheimer's disease and lysosomal storage disorders. The review covers the engineering of TfRMAb-avidin fusion proteins for BBB targeted delivery of biotinylated peptide radiopharmaceuticals, low-affinity TfRMAb Trojan horses and the safety pharmacology of chronic administration of TfRMAb fusion proteins. EXPERT OPINION: The BBB delivery of biologic drugs is possible following re-engineering as a fusion protein with a molecular Trojan horse such as a TfRMAb. The efficacy of this technology will be determined by the outcome of future clinical trials. PMID- 25138992 TI - Supportive post-implant therapy: patient compliance rates and impacting factors: 3-year follow-up. AB - AIM: To evaluate patient compliance rates and influential factors regarding a systematic SIT program. MATERIALS AND METHODS: Between 2005 and 2008, we identified all patients who were provided with implant-supported restorations in the study centre. They had been recommended to attend a SIT program with a 3 month recall. In 2012, a clinical retrospective cohort study on compliance rates over the first 3 years was performed different data were assessed in a regression analysis to identify potential influential factors. RESULTS: The inclusion criteria were met by 236 patients with 540 implants. Non-compliance rates increased over the 3 years (5.37%/7.78%/13.33%). Total non-compliance was observed in four patients (1.69%). No correlation to patient compliance was detected for "Age," "Gender," "Cardiovascular disease," "Pus/suppuration," or "Surgical case complexity." No decreasing effect of higher compliance rates on the patients' bleeding on probing (BOP+) values was found, but a statistical significance between lower compliance rates and increased pocket probing depth (PPD) was detected. The correlation between the presence of plaque and compliance did not reach statistical significance. CONCLUSIONS: When patients with implant supported restorations are strongly recommended to comply with a SIT program with a 3-month recall, considerably high rates of compliance can be achieved. PMID- 25138993 TI - Differential association between metabolic syndrome and coronary artery disease evaluated with cardiac computed tomography according to the presence of diabetes in a symptomatic Korean population. AB - BACKGROUND: Metabolic syndrome (MetS) is associated with increased risks of diabetes and coronary artery disease (CAD). Despite the controversial inclusion of established diabetes in MetS, the association between MetS and CAD according to diabetes status has not been elucidated in the Asian population. METHODS: We evaluated the association between MetS and CAD using the parameters including any plaque, obstructive plaque, and coronary artery calcium score (CACS) >100 according to diabetes status in 2,869 symptomatic Korean subjects who underwent cardiac computed tomographic angiography. RESULTS: The prevalence of MetS was significantly higher in the diabetic subjects than in the non-diabetic subjects (69% vs. 34%, P <0.001). The incidence of any plaque (64% vs. 43%, P <0.001), obstructive plaque (26% vs. 13%, P = 0.006), and CACS >100 (23% vs. 12%, P = 0.012) was significantly higher in diabetic subjects than in non-diabetic subjects. Among the MetS components, decreased high-density lipoprotein level was significantly associated with any plaque (odds ratio [OR] 1.35), obstructive plaque (OR 1.55), and CACS >100 (OR 1.57) in the non-diabetic subjects (P <0.01, respectively). However, none of the MetS components were associated with all the parameters in the diabetic subjects. Multivariate regression analysis revealed that MetS and the number of MetS components (MetSN) were independently associated with any plaque (MetS: OR 1.55, P <0.001; MetSN: OR 1.22, P <0.001), obstructive plaque (MetS: OR 1.52, P = 0.003; MetSN: OR 1.25, P <0.001), and CACS >100 (MetS: OR 1.46, P = 0.015; MetSN: OR 1.21, P = 0.004) only in the non-diabetic subjects, respectively. CONCLUSIONS: MetS was independently associated with the presence and severity of CAD only in the non-diabetic subjects among the symptomatic Korean population. PMID- 25138995 TI - Mental disorder and suicide: a faulty connection. PMID- 25138994 TI - Developing zebrafish models relevant to PTSD and other trauma- and stressor related disorders. AB - While post-traumatic stress disorder (PTSD) and other trauma- and stress-related disorders (TSRDs) represent a serious societal and public health concern, their pathogenesis is largely unknown. Given the clinical complexity of TSRD development and susceptibility, greater investigation into candidate biomarkers and specific genetic pathways implicated in both risk and resilience to trauma becomes critical. In line with this, numerous animal models have been extensively used to better understand the pathogenic mechanisms of PTSD and related TSRD. Here, we discuss the rapidly increasing potential of zebrafish as models of these disorders, and how their use may aid researchers in uncovering novel treatments and therapies in this field. PMID- 25138996 TI - 'I move therefore I am': the anoetic ideomotor theory of autism. PMID- 25138997 TI - The importance of mental disorders in suicide. PMID- 25138999 TI - Training experience in gestures affects the display of social gaze in baboons' communication with a human. AB - Gaze behaviour, notably the alternation of gaze between distal objects and social partners that accompanies primates' gestural communication is considered a standard indicator of intentionality. However, the developmental precursors of gaze behaviour in primates' communication are not well understood. Here, we capitalized on the training in gestures dispensed to olive baboons (Papio anubis) as a way of manipulating individual communicative experience with humans. We aimed to delineate the effects of such a training experience on gaze behaviour displayed by the monkeys in relation with gestural requests. Using a food requesting paradigm, we compared subjects trained in requesting gestures (i.e. trained subjects) to naive subjects (i.e. control subjects) for their occurrences of (1) gaze behaviour, (2) requesting gestures and (3) temporal combination of gaze alternation with gestures. We found that training did not affect the frequencies of looking at the human's face, looking at food or alternating gaze. Hence, social gaze behaviour occurs independently from the amount of communicative experience with humans. However, trained baboons-gesturing more than control subjects-exhibited most gaze alternation combined with gestures, whereas control baboons did not. By reinforcing the display of gaze alternation along with gestures, we suggest that training may have served to enhance the communicative function of hand gestures. Finally, this study brings the first quantitative report of monkeys producing requesting gestures without explicit training by humans (controls). These results may open a window on the developmental mechanisms (i.e. incidental learning vs. training) underpinning gestural intentional communication in primates. PMID- 25139000 TI - Predators in training: operant conditioning of novel behavior in wild Burmese pythons (Python molurus bivitattus). AB - Large pythons and boas comprise a group of animals whose anatomy and physiology are very different from traditional mammalian, avian and other reptilian models typically used in operant conditioning. In the current study, investigators used a modified shaping procedure involving successive approximations to train wild Burmese pythons (Python molurus bivitattus) to approach and depress an illuminated push button in order to gain access to a food reward. Results show that these large, wild snakes can be trained to accept extremely small food items, associate a stimulus with such rewards via operant conditioning and perform a contingent operant response to gain access to a food reward. The shaping procedure produced robust responses and provides a mechanism for investigating complex behavioral phenomena in massive snakes that are rarely studied in learning research. PMID- 25138998 TI - The opioid system and brain development: effects of methadone on the oligodendrocyte lineage and the early stages of myelination. AB - Oligodendrocytes express opioid receptors throughout development, but the role of the opioid system in myelination remains poorly understood. This is a significant problem as opioid use and abuse continue to increase in two particular populations: pregnant addicts (in whom drug effects could target early myelination in the fetus and newborn) and adolescents and young adults (in whom late myelination of 'higher-order' regions takes place). Maintenance treatments for opioid addicts include the long-lasting opioids methadone and buprenorphine. Similar to our previous findings on the effects of buprenorphine, we have now found that early myelination in the developing rat brain is also altered by perinatal exposure to therapeutic doses of methadone. Pups exposed to this drug exhibited elevated brain levels of the 4 major splicing variants of myelin basic protein, myelin proteolipid protein, and myelin-oligodendrocyte glycoprotein. Consistent with the enrichment and function of these proteins in mature myelin, analysis of the corpus callosum in these young animals also indicated an elevated number of axons with already highly compacted myelin sheaths. Moreover, studies in cultured cells showed that methadone exerts direct effects at specific stages of the oligodendrocyte lineage, stimulating the proliferation of progenitor cells while on the other hand accelerating the maturation of the more differentiated but still immature preoligodendrocytes. While the long-term effects of these observations remain unknown, accelerated or increased oligodendrocyte maturation and myelination could both disrupt the complex sequence of synchronized events leading to normal connectivity in the developing brain. Together with our previous observations on the effects of buprenorphine, the present findings further underscore a crucial function of the endogenous opioid system in the control of oligodendrocyte development and the timing of myelination. Interference with these regulatory systems by opioid use or maintenance treatments could disrupt the normal process of brain maturation at critical stages of myelin formation. PMID- 25139001 TI - Changes in perceptual speed and white matter microstructure in the corticospinal tract are associated in very old age. AB - The integrity of the brain's white matter is important for neural processing and displays age-related differences, but the contribution of changes in white matter to cognitive aging is unclear. We used latent change modeling to investigate this issue in a sample of very old adults (aged 81-103 years) assessed twice with a retest interval of 2.3 years. Using diffusion-tensor imaging, we probed white matter microstructure by quantifying mean fractional anisotropy and mean diffusivity of six major white matter tracts. Measures of perceptual speed, episodic memory, letter fluency, category fluency, and semantic memory were collected. Across time, alterations of white matter microstructure in the corticospinal tract were associated with decreases of perceptual speed. This association remained significant after statistically controlling for changes in white matter microstructure in the entire brain, in the other demarcated tracts, and in the other cognitive abilities. Changes in brain volume also did not account for the association. We conclude that white matter microstructure is a potent correlate of changes in sensorimotor aspects of behavior in very old age, but that it is unclear whether its impact extends to higher-order cognition. PMID- 25139003 TI - Magnetic resonance imaging evaluation of lipodystrophy in HIV-positive patients receiving highly active antiretroviral therapy. AB - We evaluated retrospectively an automated method for the separate detection of subcutaneous and visceral fat in the abdominal region by magnetic resonance studies in HIV-positive patients on highly active antiretroviral therapy. The patients were divided into four different groups: lipoatrophy, lipohypertrophy, mixed and the control group. The use of software for the automated detection of abdominal compartment visceral adipose tissue (VAT), total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) was compared to manual evaluation methods (fuzzy C-mean). The results of ROC analysis showed that the parameters, particularly the VAT, are better than the VAT/TAT and at identifying patients with the symptoms of abdominal fat accumulation. A sensitivity of 80.3% and a specificity of 79.5% resulted from a threshold VAT value of >87 cm(2). Moreover, the manual evaluation method was shown to provide greater values for VAT and the VAT/TAT ratio than those given by the automated method. In the present study, a rapid MRI protocol for the detection and assessment of the course of lipodystrophy was presented and tested on a group of patients with signs of HALS, as well as on an antiretroviral naive control group. PMID- 25139004 TI - Access to post-exposure prophylaxis following sexual exposure for men who have sex with men in an Irish healthcare setting. AB - Men who have sex with men experience disproportionate rates of HIV acquisition. Post-exposure prophylaxis following unprotected sexual exposure reduces HIV transmission. Our aim was to assess access to post-exposure prophylaxis for men who have sex with men in Irish emergency departments. We contacted all national 24-hour adult emergency departments describing two scenarios; a seronegative man who has sex with men receiving unprotected insertive anal intercourse from a seropositive partner and secondly a woman sustaining a needle-stick injury from an unknown source. We recorded and compared responses regarding post-exposure prophylaxis advice in each situation. High proportions of emergency departments offered post-exposure prophylaxis for both situations despite minimal evidence to support use in needle-stick injury. Men who have sex with men were less likely to be asked to attend emergency departments for post-exposure prophylaxis administration than a person experiencing needle-stick injury. Men who have sex with men were less likely to be offered baseline serological testing for blood borne infections. Men who have sex with men were as likely as needle-stick injury to receive advice from healthcare workers in emergency departments and consultation durations were similar. This study identifies a need to educate healthcare workers in emergency departments on appropriate use of post-exposure prophylaxis following sexual exposure for men who have sex with men. Health care workers must appreciate the importance of post-exposure prophylaxis presentations as opportunities for intervention and HIV screening. PMID- 25139002 TI - Reduced mediodorsal thalamic volume and prefrontal cortical spindle activity in schizophrenia. AB - BACKGROUND: We recently found marked deficits in sleep spindles, non-rapid eye movement (NREM) sleep oscillations that are generated within the thalamus and then amplified and sustained in the cortex, in patients with schizophrenia compared to both healthy and psychiatric controls. Here, we investigated the thalamic and cortical contributions to these sleep spindle deficits. METHODS: Anatomical volume of interest analysis (i.e., thalamic volumes) and electroencephalogram (EEG) source modeling (i.e., spindle-related cortical currents) were performed in patients with schizophrenia and healthy comparison subjects. FINDINGS: Schizophrenia patients had reduced mediodorsal (MD) thalamic volumes, especially on the left side, compared to healthy controls, whereas whole thalami and lateral geniculate nuclei did not differ between groups. Furthermore, left MD volumes were strongly correlated with the number of scalp-recorded spindles in an anterior frontal region, and cortical currents underlying these anterior frontal spindles were localized in the prefrontal cortex, in Brodmann area (BA) 10. Finally, prefrontal currents at the peak of spindle activity were significantly reduced in schizophrenia patients and correlated with their performance in an abstraction/working memory task. CONCLUSION: Altogether, these findings point to deficits in a specific thalamo-cortical circuitry in schizophrenia, which is associated with some cognitive deficits commonly reported in those patients. PMID- 25139005 TI - Model-assisted analysis of sugar metabolism throughout tomato fruit development reveals enzyme and carrier properties in relation to vacuole expansion. AB - A kinetic model combining enzyme activity measurements and subcellular compartmentation was parameterized to fit the sucrose, hexose, and glucose-6-P contents of pericarp throughout tomato (Solanum lycopersicum) fruit development. The model was further validated using independent data obtained from domesticated and wild tomato species and on transgenic lines. A hierarchical clustering analysis of the calculated fluxes and enzyme capacities together revealed stage dependent features. Cell division was characterized by a high sucrolytic activity of the vacuole, whereas sucrose cleavage during expansion was sustained by both sucrose synthase and neutral invertase, associated with minimal futile cycling. Most importantly, a tight correlation between flux rate and enzyme capacity was found for fructokinase and PPi-dependent phosphofructokinase during cell division and for sucrose synthase, UDP-glucopyrophosphorylase, and phosphoglucomutase during expansion, thus suggesting an adaptation of enzyme abundance to metabolic needs. In contrast, for most enzymes, flux rates varied irrespectively of enzyme capacities, and most enzymes functioned at <5% of their maximal catalytic capacity. One of the major findings with the model was the high accumulation of soluble sugars within the vacuole together with organic acids, thus enabling the osmotic-driven vacuole expansion that was found during cell division. PMID- 25139006 TI - Functional characterization of the small regulatory subunit PetP from the cytochrome b6f complex in Thermosynechococcus elongatus. AB - The cyanobacterial cytochrome b(6)f complex is central for the coordination of photosynthetic and respiratory electron transport and also for the balance between linear and cyclic electron transport. The development of a purification strategy for a highly active dimeric b(6)f complex from the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1 enabled characterization of the structural and functional role of the small subunit PetP in this complex. Moreover, the efficient transformability of this strain allowed the generation of a DeltapetP mutant. Analysis on the whole-cell level by growth curves, photosystem II light saturation curves, and P700(+) reduction kinetics indicate a strong decrease in the linear electron transport in the mutant strain versus the wild type, while the cyclic electron transport via photosystem I and cytochrome b(6)f is largely unaffected. This reduction in linear electron transport is accompanied by a strongly decreased stability and activity of the isolated DeltapetP complex in comparison with the dimeric wild-type complex, which binds two PetP subunits. The distinct behavior of linear and cyclic electron transport may suggest the presence of two distinguishable pools of cytochrome b(6)f complexes with different functions that might be correlated with supercomplex formation. PMID- 25139007 TI - A mitogen-activated protein kinase cascade module, MKK3-MPK6 and MYC2, is involved in blue light-mediated seedling development in Arabidopsis. AB - Mitogen-activated protein kinase (MAPK) pathways are involved in several signal transduction processes in eukaryotes. Light signal transduction pathways have been extensively studied in plants; however, the connection between MAPK and light signaling pathways is currently unknown. Here, we show that MKK3-MPK6 is activated by blue light in a MYC2-dependent manner. MPK6 physically interacts with and phosphorylates a basic helix-loop-helix transcription factor, MYC2, and is phosphorylated by a MAPK kinase, MKK3. Furthermore, MYC2 binds to the MPK6 promoter and regulates its expression in a feedback regulatory mechanism in blue light signaling. We present mutational and physiological studies that illustrate the function of the MKK3-MPK6-MYC2 module in Arabidopsis thaliana seedling development and provide a revised mechanistic view of photomorphogenesis. PMID- 25139008 TI - Riluzole likely lacks antidepressant efficacy in ketamine non-responders. PMID- 25139010 TI - Pertussis in Latin America: epidemiology and control strategies. AB - Pertussis is a serious respiratory disease in infants that can also affect children and adults. Vaccination against pertussis was introduced in the 1950s and in the 1990s a resurgence of pertussis was observed worldwide. The aim of this work is to summarize the recent data concerning pertussis disease in different countries of Latin America. In this geographic region, pertussis is nationally notifiable and cases should be reported to the appropriate health department/Ministry. Though the surveillance systems are not the same among Latin America countries, over recent decades an increasing number of cases have been detected. Most of these cases correspond to patients younger than 6 months old who received fewer than three doses of vaccine. However, cases in adolescent and adults have also been detected. For this situation, which is not peculiar to Latin America countries, several explanations have been proposed. PMID- 25139011 TI - Validation of a web-based questionnaire to assess the dietary intake of Brazilian children aged 7-10 years. AB - BACKGROUND: The Food Intake and Physical Activity of School Children (CAAFE) comprises an online questionnaire to self-report diet and physical activity of Brazilian schoolchildren. BACKGROUND: The present study aimed to assess the validity (matches, omissions and intrusions) and moderating factors of the CAAFE. METHODS: Direct observation was made of foods consumed (five public schools) and child self-reporting on the CAAFE. Additional data included school grade, gender, body mass index, completion of food diary, socioeconomic status and access to computer. Data were analysed using regression. RESULTS: In total, 602 children participated in the study [mean (SD) age 9.5 (1.24) years; 53.6% boys]. On average, there were 43% matches, 29% intrusions and 28% omissions. Matches doubled in third grade compared to the second grade (P = 0.004); matches almost tripled for afternoon snack compared to morning snack (P < 0.001); and matches were 69% higher for children with access to a computer at home (P < 0.01). Intrusions decreased by almost one-half in fifth compared to fourth grades (P = 0.004). Omissions declined significantly in the third and fourth grades but increased in the fifth grade. Omissions were 47% lower for children in the highest income and lower among children who completed the food diary. No differences were found for gender or body mass index. CONCLUSIONS: Children older than 8 years old, who owned a computer and completed a food diary, performed better in the CAAFE. A high incidence of disagreement was found in relation to the schools and the type of meal. Overall matches (43%), intrusions (29%) and omissions (28%) indicate that further studies are required to improve the validity of the CAAFE. PMID- 25139009 TI - The cumulative effect of different childhood trauma types on self-reported symptoms of adult male depression and PTSD, substance abuse and health-related quality of life in a large active-duty military cohort. AB - History of childhood trauma (CT) is highly prevalent and may lead to long-term consequences on physical and mental health. This study investigated the independent association of CT with symptoms of adult depression and posttraumatic stress disorder (PTSD), mental and physical health-related quality of life (HRQoL), as well as current tobacco consumption and alcohol abuse in a large homogenous cohort of 1254 never-deployed, young male Marines enrolled in the Marine Resiliency Study. Independent effects of CT history, number and type of CT on outcomes were analyzed using hierarchical multivariate logistic regression models. Our results suggested dose-dependent negative effect of an increasing number of trauma types of CT on depression, PTSD and HRQoL. Experience of single CT type demonstrated overall weak effects, while history of multiple CT types distinctively increased the likelihood of adult PTSD symptomology (OR: 3.1, 95% CI: 1.5-6.2), poor mental (OR: 2.3, 95% CI: 1.7-3.1) and physical HRQoL (OR: 1.4, 95% CI: 1.1-1.9). Risk for depression symptoms was similar for both single and multiple CT (OR: 2.2, 95% CI: 1.3-3.8 and OR: 2.1, 95% CI: 1.2-3.5 respectively). CT history had no effects on current tobacco use and alcohol abuse. Our study thus provides evidence for substantial additive effect of different CT types on adult mental and physical health with increasing levels of exposure. PMID- 25139013 TI - Enhanced resistance of CXCR3 deficient mice to ocular HSV-1 infection is due to control of replication in the brain ependyma. AB - CXCR3 deficient (CXCR3(-/-)) mice are resistant to ocular HSV-1 infection in that less mice develop encephalitis and succumb to infection in comparison to wild type (WT) animals. A region of the brain previously identified to be crucial for development of encephalitis was evaluated in HSV-1-infected CXCR3(-/-) and WT mice. In this region, known as the ependyma, viral titer, infiltrating leukocyte populations, and key anti-viral cytokine message levels were evaluated. We found that CXCR3(-/-) mice possessed significantly less HSV-1 and expressed significantly more IFN-beta mRNA in the brain ependyma compared to WT animals during the development of encephalitis. PMID- 25139014 TI - Immunosuppressants increase the levels of natural autoantibodies reactive with glycosaminoglycans in myasthenia gravis. AB - Increasing number of evidences support the role of glycosylation in the evolution of autoimmunity. We examined carbohydrate-reactive natural autoantibodies systematically for the first time in patients with autoimmune myasthenia gravis. Antibodies reactive to glycosaminoglycans were measured with CovaLink ELISA in the sera of 59 myasthenia patients as well as in 54 healthy controls. We used the GlycoChip carbohydrate array to characterize individual carbohydrate recognition patterns. Chondroitin-sulphate C and anti-alpha-mannose-specific IgG levels were significantly elevated in myasthenia patients. Unexpectedly, we found that immunosuppressants increased the levels of the protective IgM glycosaminoglycan reactive natural antibodies demonstrating a new role for these agents in immunoregulation. PMID- 25139015 TI - Comparison of computed tomographic and pathologic findings in 17 dogs with primary adrenal neoplasia. AB - The CT appearance of canine adrenal masses has been reported, but associations between imaging features and pathologic features of these lesions have not been investigated in detail. The purpose of this study was to test associations between different types of adrenal neoplasia and their CT and pathologic features. A retrospective cross-sectional study was performed and inclusion criteria were histologic diagnosis of primary adrenal neoplasia, contrast enhanced CT examination of the abdomen and surgical resection of the mass or necropsy examination. For all included dogs, CT images and histopathologic specimens were reviewed independently by two veterinary radiologists and a veterinary pathologist, respectively. Seventeen dogs met inclusion criteria. Diagnoses were adenocarcinoma in nine (53%) dogs, pheochromocytoma in five (29%) dogs, and adenoma in three (18%) dogs. Pheochromocytoma was associated with CT signs of vascular invasion (likelihood ratio = 4.8, 95% CI = 1.3-18.3, P = 0.03) and macroscopic vascular invasion (likelihood ratio = 9.6, 95% CI = 1.4-65.9, P = 0.02). There was excellent agreement between signs of vascular invasion in CT images and vascular invasion at surgery or necropsy (kappa = 0.86, P = 0.001). A peripheral contrast-enhancing rim in delayed postcontrast CT images was associated with fibrous encapsulation of the tumor (kappa = 0.53, P = 0.05), and a heterogeneous pattern of contrast distribution in delayed postcontrast CT images was associated with adrenal hemorrhage or infarction on histological examination (kappa = 0.45, P = 0.05). Findings indicated that CT enabled assessment of adrenal neoplasia features that reflected their biological behavior and pathological findings, however overlapping characteristics between tumor types limited the potential for reliably distinguishing them based on CT alone. PMID- 25139016 TI - Intermediate monocytes contribute to pathologic immune response in Leishmania braziliensis infections. AB - Ulcer development in patients with cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is associated with high levels of tumor necrosis factor (TNF). We found that early after infection, before ulcer development, the frequency of CD16(+) (both intermediate [CD14(+)CD16(+)] and nonclassical [CD14(dim)CD16(+)]) monocytes was increased in the peripheral blood of patients with L. braziliensis, compared with uninfected controls. These results suggest that CD16(+) monocytes might promote disease. Also, we found that intermediate monocytes expressed CCR2 and that increased levels of CCL2 protein were present in lesions from patients, suggesting that intermediate monocytes are more likely than nonclassical monocytes to migrate to the lesion site. Finally, we found that the intermediate monocytes produced TNF. Our results show that intermediate monocytes are increased in frequency soon after infection; express CCR2, which would promote their migration into the lesions; and, owing to their production of TNF, can enhance the inflammatory response. PMID- 25139017 TI - Probing of a human proteome microarray with a recombinant pathogen protein reveals a novel mechanism by which hookworms suppress B-cell receptor signaling. AB - Na-ASP-2 is an efficacious hookworm vaccine antigen. However, despite elucidation of its crystal structure and studies addressing its immunobiology, the function of Na-ASP-2 has remained elusive. We probed a 9000-protein human proteome microarray with Na-ASP-2 and showed binding to CD79A, a component of the B-cell antigen receptor complex. Na-ASP-2 bound to human B lymphocytes ex vivo and downregulated the transcription of approximately 1000 B-cell messenger RNAs (mRNAs), while only approximately 100 mRNAs were upregulated, compared with control-treated cells. The expression of a range of molecules was affected by Na ASP-2, including factors involved in leukocyte transendothelial migration pathways and the B-cell signaling receptor pathway. Of note was the downregulated transcription of lyn and pi3k, molecules that are known to interact with CD79A and control B-cell receptor signaling processes. Together, these results highlight a previously unknown interaction between a hookworm-secreted protein and B cells, which has implications for helminth-driven immunomodulation and vaccine development. Further, the novel use of human protein microarrays to identify host-pathogen interactions, coupled with ex vivo binding studies and subsequent analyses of global gene expression in human host cells, demonstrates a new pipeline by which to explore the molecular basis of infectious diseases. PMID- 25139019 TI - Dietary pectin-derived acidic oligosaccharides improve the pulmonary bacterial clearance of Pseudomonas aeruginosa lung infection in mice by modulating intestinal microbiota and immunity. AB - BACKGROUND: A predominantly T-helper type 2 (Th2) immune response is critical in the prognosis of pulmonary Pseudomonas aeruginosa infection. But the mucosal and systemic immune responses can be influenced by the intestinal microbiota. METHODS: We assessed the effect of microbiota compositional changes induced by a diet enriched in 5% acidic oligosaccharides derived from pectin (pAOS) on the immune response and outcome of chronic pulmonary P. aeruginosa infection in mice. RESULTS: pAOS promoted Th1 polarization by increasing interferon gamma release, upregulating t-bet gene expression, decreasing interleukin 4 secretion, and downregulating gata3 gene expression. pAOS also sustained the release of keratinocyte chemoattractant, recruited polynuclear leukocytes and macrophages, stimulated M1 macrophage activation and interleukin 10 release, and decreased tumor necrosis factor alpha release in the lung. These effects led to increased bacterial clearance after the first and second P. aeruginosa infections. pAOS modified the intestinal microbiota by stimulating the growth of species involved in immunity development, such as Bifidobacterium species, Sutturella wadsworthia, and Clostridium cluster XIVa organisms, and at the same time increased the production of butyrate and propionate. CONCLUSION: These results suggest that pAOS may have beneficial effects by limiting the number and severity of pulmonary exacerbations in patients chronically infected with P. aeruginosa, such as individuals with cystic fibrosis. PMID- 25139018 TI - Human papillomavirus 16-specific T-cell responses and spontaneous regression of anal high-grade squamous intraepithelial lesions. AB - BACKGROUND: Most anal cancers are attributable to persistent human papillomavirus type 16 (HPV-16) infection. The anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), frequently regresses spontaneously. We hypothesized that T-cell responses are associated with HSIL regression. METHODS: In men who have sex with men undergoing anal cytology and high-resolution anoscopy, we measured responses to HPV-16 oncogenic proteins E6 and E7, using the CD25/CD134 assay for CD4(+) antigen-specific T cells and intracellular cytokine staining for CD4(+) and CD8(+) antigen-specific T cells. RESULTS: Of 134 participants (mean [SD] age, 51 [9.3] years; 31 [23.1%] infected with human immunodeficiency virus), 51 (38.1%) had HSIL. E6- and E7-specific CD4(+) T-cell responses were detected in 80 (59.7%) and 40 (29.9%) of the participants, respectively, and E6- and E7-specific CD8(+) T-cell responses were each detected in 25 (18.7%). HSIL was significantly associated with E7-specific CD8(+) T-cell responses (odds ratio, 4.09 [95% confidence interval, 1.55-10.77], P = .004), but not with any CD4(+) T-cell response (P >= .09). Twenty-six participants had HSIL a mean of 1 year before measurement of T-cell responses, and 6 (23%) of them were regressors. Five regressors (83%) had E6-specific CD4(+) T-cell responses vs 7 of 20 (35%) nonregressors (Pexact = .065). CONCLUSIONS: Systemic HPV-16 E6- and E7 specific T-cell responses were common in men who have sex with men. E6-specific CD4(+) T-cell responses may be associated with recent HSIL regression. CLINICAL TRIALS REGISTRATION: NCT02007421. PMID- 25139020 TI - BB0323 and novel virulence determinant BB0238: Borrelia burgdorferi proteins that interact with and stabilize each other and are critical for infectivity. AB - We have shown that Borrelia burgdorferi gene product BB0323 is essential for cell fission and pathogen persistence in vivo. Here we describe characterization of a conserved hypothetical protein annotated as BB0238, which specifically interacts with the N-terminal region of BB0323. We show that BB0238 is a subsurface protein, and similar to BB0323, exists in the periplasm and as a membrane-bound protein. Deletion of bb0238 in infectious B. burgdorferi did not affect microbial growth in vitro or survival in ticks, but the mutant was unable to persist in mice or transmit from ticks--defects that are restored on genetic complementation. Remarkably, BB0238 and BB0323 contribute to mutual posttranslational stability, because deletion of one causes dramatic reduction in the protein level of the other partner. Interference with the function of BB0238 or BB0323 and their interaction may provide novel strategies to combat B. burgdorferi infection. PMID- 25139021 TI - Basis of virulence in a Panton-Valentine leukocidin-negative community-associated methicillin-resistant Staphylococcus aureus strain. AB - Community-associated (CA) infections with methicillin-resistant Staphylococcus aureus (MRSA) are on a global rise. However, analysis of virulence characteristics has been limited almost exclusively to the US endemic strain USA300. CA-MRSA strains that do not produce Panton-Valentine leukocidin (PVL) have not been investigated on a molecular level. Therefore, we analyzed virulence determinants in a PVL-negative CA-MRSA strain, ST72, from Korea. Genome-wide analysis identified 3 loci that are unique to that strain, but did not affect virulence. In contrast, phenol-soluble modulins (PSMs) and the global virulence regulator Agr strongly affected lysis of neutrophils and erythrocytes, while alpha-toxin and Agr had a major impact on in vivo virulence. Our findings substantiate the general key roles these factors play in CA-MRSA virulence. However, our analyses also showed noticeable differences to strain USA300, inasmuch as alpha-toxin emerged as a much more important factor than PSMs in experimental skin infection caused by ST72. PMID- 25139022 TI - Tr-1-like CD4+CD25-CD127-/lowFOXP3- cells are the main source of interleukin 10 in patients with cutaneous leishmaniasis due to Leishmania braziliensis. AB - CD4(+)CD25(+)FOXP3(+) regulatory T cells have long been shown to mediate susceptibility to Leishmania infection, mainly via interleukin 10 production. In this work, we showed that the main sources of interleukin 10 in peripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis due to Leishmania braziliensis are CD4(+)CD25(-)CD127(-/low)FOXP3(-) cells. Compared with uninfected controls, patients with CL had increased frequencies of circulating interleukin 10-producing CD4(+)CD25(-)CD127(-/low) cells, which efficiently suppressed tumor necrosis factor alpha production by the total PBMC population. Also, in CL lesions, interleukin 10 was mainly produced by CD4(+)CD25(-) cells, and interleukin 10 messenger RNA expression was associated with interleukin 27, interleukin 21, and interferon gamma expression, rather than with FOXP3 or transforming growth factor beta expressions. Active production of both interleukin 27 and interleukin 21, together with production of interferon gamma and interleukin 10, was also detected in the lesions. Since these cytokines are associated with the differentiation and activity of Tr-1 cells, our results suggest that this cell population may play an important role in the immunomodulation of CL. Therefore, development of treatments that interfere with this pathway may lead to faster parasite elimination. PMID- 25139023 TI - Fetal origins of malarial disease: cord blood cytokines as risk markers for pediatric severe malarial anemia. AB - BACKGROUND: Severe malarial anemia (SMA) remains a major cause of pediatric illness and mortality in Sub-Saharan Africa. Here we test the hypothesis that prenatal exposures, reflected by soluble inflammatory mediators in cord blood, can condition an individual's susceptibility to SMA. METHODS: In a Tanzanian birth cohort (n = 743), we measured cord blood concentrations of tumor necrosis factor (TNF), TNF receptors I and II (TNF-RI and TNF-RII), interleukin (IL) 1beta, IL-4, IL-5, IL-6, IL-10, and interferon gamma (IFN-gamma). After adjusting for conventional covariates, we calculated the hazard ratios (HR) for time to first SMA event with log(e) cytokine concentrations dichotomized at the median, by quartile, and per standard deviation (SD) increase. RESULTS: Low levels of TNF, TNF-RI, IL-1beta, and IL-5 and high levels of TNF-RII were associated statistically significantly and respectively with approximately 3-fold, 2-fold, 8 fold, 4-fold, and 3-fold increased risks of SMA (Hb < 50 g/L). TNF, TNF-RI, and IL-1beta concentrations were inversely and log-linearly associated with SMA risk; the HR (95% confidence interval [CI]) per 1-SD increase were respectively 0.81 (.65, 1.02), 0.76 (.62, .92), and 0.50 (.40, .62). CONCLUSIONS: These data suggest that proinflammatory cytokine levels at birth are inversely associated with SMA risk and support the hypothesis that pediatric malarial disease has fetal origins. PMID- 25139024 TI - MiR-136 targets E2F1 to reverse cisplatin chemosensitivity in glioma cells. AB - MicroRNAs (miRNAs) have gained much attention due to their critical roles in diverse biological events, including tumorigenesis. In this study, we demonstrate that miR-136 is down-regulated in two cohorts of patients with glioma. Furthermore, the low-level expression of miR-136 is significantly associated with a more aggressive and/or poor prognostic phenotype of patients with gliomas. Both gain- and loss-of-function experiments showed that miR-136 expression can reverse cisplatin resistance and enhance the response to cisplatin treatment. Furthermore, we identified a novel direct target of miR-136, the E2F transcription factor 1 (E2F1) oncogene. Depletion of E2F1 recapitulated the tumor suppressive functions of miR-136, whereas re-expression of E2F1 attenuated the function of miR-136 in glioma cells. Finally, we revealed that miR-136 is inversely correlated with E2F1 expression in human glioma samples. The present study provides functional and mechanistic links between the tumor suppressor miR 136 and the oncogene E2F1 for the development of chemoresistance in human glioma. Our results indicate that targeting of the miR-136/E2F1 axis may provide a promising therapeutic approach to treat glioma. PMID- 25139026 TI - Temozolomide after radiotherapy in recurrent "low grade" diffuse brainstem glioma in adults. AB - Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is usually considered to be the standard treatment. However, the role of chemotherapy in treating relapses after RT is unclear, and this study aimed to assess the use of temozolomide (TMZ) in this situation. We conducted a retrospective analysis of patients from our database with "low grade" adult diffuse infiltrating brainstem glioma who received TMZ at relapse after failing RT. The patients were diagnosed by histology or MRI criteria compatible with a low-grade glioma. The tumors were localized in the pons, medulla oblongata or midbrain, excluding supratentorial or infratentorial tumors that had infiltrated the brainstem secondarily. The patients' clinical and radiological responses were assessed, and their progression free survival (PFS) and overall survival (OS) time were estimated. Fifteen adult patients (median age 34 years) fulfilled the inclusion criteria. Histological analysis was available in 5 cases and showed grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), and grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only. All patients received RT as initial treatment and had a median PFS of 34.2 months (95 % CI 24.1-44.2). The median KPS at the time of relapse was 80. TMZ was administered orally at 150-200 mg/m(2) for 5 days, every 28 days. Clinical improvement after TMZ was observed in 9 cases (60 %), whereas radiological assessment detected responses in 6/15 cases, including 4 partial and 2 minor responses. The estimated median PFS after TMZ was 9.5 months (95 % CI 7.9-11), and the median OS was 14.4 months (95 % CI 10.5-18.2). Grade 3 thrombopenia was observed in 26 % of cases. TMZ could be useful after RT failure in adult patients with recurrent diffuse "low grade" brainstem glioma. PMID- 25139025 TI - Co-administration of ABT-737 and SAHA induces apoptosis, mediated by Noxa upregulation, Bax activation and mitochondrial dysfunction in PTEN-intact malignant human glioma cell lines. AB - We previously observed that glioma cells are differentially sensitive to ABT-737 and, when used as a single-agent, this drug failed to induce apoptosis. Identification of therapeutic strategies to enhance the efficacy of the Bcl-2 inhibitor ABT-737 in human glioma is of interest. Histone deacetylation inhibitors (HDACI) are currently being assessed clinically in patients with glioma, as regulation of epigenetic abnormalities is expected to produce pro apoptotic effects. We hypothesized that co-treatment of glioma with a BH3-mimetic and HDACI may induce cellular death. We assessed the combination of ABT-737 and HDACI SAHA in established and primary cultured glioma cells. We found combination treatment led to significant cellular death when compared to either drug as single agent and demonstrated activation of the caspase cascade. This enhanced apoptosis also appears dependent upon the loss of mitochondrial membrane potential and the release of cytochrome c and AIF into the cytosol. The upregulation of Noxa, truncation of Bid, and activation of Bax caused by this combination were important factors for cell death and the increased levels of Noxa functioned to sequester Mcl-1. This combination was less effective in PTEN deficient glioma cells. Both genetic and pharmacologic inactivation of the PI3K/Akt signaling pathway sensitized PTEN-deleted glioma cells to the combination. This study demonstrates that antagonizing apoptosis-resistance pathways, such as targeting the Bcl-2 family in combination with epigenetic modifiers, may induce cell death. These findings extend our previous observations that targeting the PI3K/Akt pathway may be additionally necessary to promote apoptosis in cancers lacking PTEN functionality. PMID- 25139027 TI - Sequencing and de novo assembly of the red cusk-eel (Genypterus chilensis) transcriptome. AB - The red cusk-eel (Genypterus chilensis) is an endemic fish species distributed along the coasts of the Eastern South Pacific. Biological studies on this fish are scarce, and genomic information for G. chilensis is practically non-existent. Thus, transcriptome information for this species is an essential resource that will greatly enrich molecular information and benefit future studies of red cusk eel biology. In this work, we obtained transcriptome information of G. chilensis using the Illumina platform. The RNA sequencing generated 66,307,362 and 59,925,554 paired-end reads from skeletal muscle and liver tissues, respectively. De novo assembly using the CLC Genomic Workbench version 7.0.3 produced 48,480 contigs and created a reference transcriptome with a N50 of 846bp and average read coverage of 28.3*. By sequence similarity search for known proteins, a total of 21,272 (43.9%) contigs were annotated for their function. Out of these annotated contigs, 33.5% GO annotation results for biological processes, 32.6% GO annotation results for cellular components and 34.5% GO annotation results for molecular functions. This dataset represents the first transcriptomic resource for the red cusk-eel and for a member of the Ophidiimorpharia taxon. PMID- 25139028 TI - Bioaccumulation and toxicity of silver nanoparticles and silver nitrate to the soil arthropod Folsomia candida. AB - The growing use of silver nanoparticles (Ag-NP) triggered an increasing interest in their environmental fate and possible ecotoxicological impacts. To investigate the potential risk of Ag-NP to soil organisms, the springtail Folsomia candida was exposed to Ag-NP (reported diameter size 3-8 nm) and AgNO3 in Lufa 2.2 natural soil for 28 days to determine effects on survival and reproduction. Also, the kinetics of uptake and elimination of Ag were studied for F. candida exposed in Lufa 2.2 soil to Ag-NP (at 168 mg Ag/kg dry soil) and AgNO3 (at 30 and 60 mg Ag/kg dry soil). AgNO3 was toxic with an LC50 was 284 mg Ag/kg dry soil for effects on survival and EC10 and EC50 values of 47.6 and 99.5 mg Ag/kg dry soil, respectively for the effect on reproduction. These values did correspond with porewater concentrations of 0.801, 0.042 and 0.082 mg Ag/l, respectively. No effects on survival and reproduction of Ag-NP were observed up to 673 mg Ag/kg dry soil, although porewater concentration was similar to the EC50 for AgNO3. Exposure to both Ag forms caused a fast uptake of Ag, but the Ag elimination rate was significantly higher for Ag-NP than for AgNO3. Bioaccumulation factor was higher for AgNO3 (on average 5.64) than for Ag-NP (1.12). These findings indicate that silver ions are more toxic than Ag-NP and have a higher potential to accumulate in F. candida. PMID- 25139029 TI - Aquatic environmental safety assessment and inhibition mechanism of chemicals for targeting Microcystis aeruginosa. AB - Cyanobacteria are a diverse group of Gram-negative bacteria that produce an array of secondary compounds with selective bioactivity against vertebrates, invertebrates, fungi, bacteria and cell lines. Recently the main methods of controlling cyanobacteria are using chemicals, medicinal plants and microorganism but fewer involved the safety research in hydrophytic ecosystems. In search of an environmentally safe compound, 53 chemicals were screened against the developed heavy cyanobacteria bloom Microcystis aeruginosa using coexistence culture system assay. The results of the coexistence assay showed that 9 chemicals inhibited M. aeruginosa effectively at 20 mg L(-1) after 7 days of exposure. Among them dimethomorph, propineb, and paraquat were identified that they are safe for Chlorella vulgaris, Scenedesmus obliquus, Carassius auratus (Goldfish) and Bacillus subtilis within half maximal effective concentration (EC50) values 5.2, 4.2 and 0.06 mg L(-1) after 7 days, respectively. Paraquat as the positive control observed to be more efficient than the other compounds with the inhibitory rate (IR) of 92% at 0.5 mg L(-1). For the potential inhibition mechanism, the chemicals could destroy the cell ultrastructure in different speed. The safety assay proved dimethomorph, propineb and paraquat as harmless formulations or products having potential value in M. aeruginosa controlling, with the advantage of its cell morphology degrading ability. PMID- 25139031 TI - Investigation on bacterial community and diversity in the multilayer aquifer aquitard system of the Pearl River Delta, China. AB - Bacteria play an important role in groundwater chemistry. The groundwater resource in the Pearl River Delta (PRD) is responsible for 50 million people's water requirement. High amount of ammonium, arsenic and methane had been reported in groundwater of the PRD, which was considered as the result of intensive bacterial metabolism in the multilayer aquifer-aquitard system. To investigate bacterial community in this system and its relation with groundwater chemistry, sediment and groundwater samples were taken from representative locations in the PRD at different lithological units. Bacterial 16S rRNA gene clone libraries were constructed for microbial identifications and community structures in different strata. Canonical correlation analysis between bacterial linages and environment variables (Cl(-), PO4(3-), SO4(2-), NH4(+)) showed that community structures were significantly modified by geological conditions. Higher bacterial diversity was observed in samples from the Holocene aquitard M1 and aquifer T1, while in the older aquitard M2 and basal aquifer T2, bacterial diversity was much lower. Chloroflexi, gamma-proteobacteria and delta-proteobacteria were the dominant phyla in the aquitard sediment. beta-proteobacteria was the dominant phylum in sediment which was strongly influenced by fresh water. The results of this study demonstrated that bacterial community contains information of geological events such as sea transgression and deltaic evolution, and microbes in the aquitards have great potential in dominating groundwater quality in aquifers. PMID- 25139030 TI - Modification of the brain proteome of Africanized honeybees (Apis mellifera) exposed to a sub-lethal doses of the insecticide fipronil. AB - Fipronil is a phenylpyrazole insecticide that is widely used in Brazilian agriculture for pest control. Although honeybees are not targets of fipronil, studies indicate that this pesticide can be harmful to honeybees. To assess the effects of fipronil in the brain of Africanized Apis mellifera workers, this study focused on the toxico-proteome profiling of the brain of newly emerged and aged honeybee workers that were exposed to a sub-lethal dose (10 pg fipronil per day. i.e. (1)/100 of LD50/bee/day during 5 days) of the insecticide. Proteomic analysis identified 25 proteins that were differentially up-regulated or down regulated when the fipronil-exposed and non-exposed groups were compared. These proteins are potentially related to pathogen susceptibility, neuronal chemical stress, neuronal protein misfolding, and occurrence of apoptosis, ischemia, visual impairment, damaged synapse formation, brain degeneration, memory and learning impairment. The exposure of honeybees to a very low dose of fipronil, even for a short period of time (5 days), was sufficient to cause a series of important neuroproteomic changes in the brains of honeybees. PMID- 25139032 TI - Perchlorate-induced oxidative stress in isolated liver mitochondria. AB - As a new threat to environment all through the world, perchlorate (ClO4(-)) was predominantly a thyrotoxin, and its toxic manifestations in non-thyroid were also documented. To date, little is known about the effect of ClO4(-) on cell and organelle. To reveal the toxicity of ClO4(-) on living organism in-depth, mitochondria isolated from liver of Carassius auratus were incubated with different concentrations of ClO4(-). The results demonstrated that ClO4(-) induced mitochondrial oxidative stress, and subsequently caused a gradual opening of permeability transition pore leading to mitochondrial swelling and lipid peroxidative membrane damage. ClO4(-) has a conspicuous inhibition of electron transport chain activity which largely correlated to complexes I and IV. The investigations clearly demonstrated the oxidative stress of ClO4(-) in mitochondria, may well reveal cytotoxic effects in vitro that merit further investigation. PMID- 25139033 TI - Arsenic release from shallow aquifers of the Hetao basin, Inner Mongolia: evidence from bacterial community in aquifer sediments and groundwater. AB - Indigenous microbes play crucial roles in arsenic mobilization in high arsenic groundwater systems. Databases concerning the presence and the activity of microbial communities are very useful in evaluating the potential of microbe mediated arsenic mobilization in shallow aquifers hosting high arsenic groundwater. This study characterized microbial communities in groundwaters at different depths with different arsenic concentrations by DGGE and one sediment by 16S rRNA gene clone library, and evaluated arsenic mobilization in microcosm batches with the presence of indigenous bacteria. DGGE fingerprints revealed that the community structure changed substantially with depth at the same location. It indicated that a relatively higher bacterial diversity was present in the groundwater sample with lower arsenic concentration. Sequence analysis of 16S rRNA gene demonstrated that the sediment bacteria mainly belonged to Pseudomonas, Dietzia and Rhodococcus, which have been widely found in aquifer systems. Additionally, NO3(-)-reducing bacteria Pseudomonas sp. was the largest group, followed by Fe(III)-reducing, SO4(2-)-reducing and As(V)-reducing bacteria in the sediment sample. These anaerobic bacteria used the specific oxyanions as electron acceptor and played a significant role in reductive dissolution of Fe oxide minerals, reduction of As(V), and release of arsenic from sediments into groundwater. Microcosm experiments, using intact aquifer sediments, showed that arsenic release and Fe(III) reduction were microbially mediated in the presence of indigenous bacteria. High arsenic concentration was also observed in the batch without amendment of organic carbon, demonstrating that the natural organic matter in sediments was the potential electron donor for microbially mediated arsenic release from these aquifer sediments. PMID- 25139034 TI - The source apportionment of polycyclic aromatic hydrocarbons (PAHs) in the topsoil in Xiaodian sewage irrigation area, North of China. AB - 31 topsoil samples were collected by grid method in Xiaodian sewage irrigation area, Taiyuan City, North of China. The concentrations of 16 kinds of polycyclic aromatic hydrocarbons (PAHs) were determined by gas chromatograph coupled with mass spectrum. Generally speaking, the distribution order of PAHs in the area is: those with five and six rings > those with four rings > those with two and three rings. Source apportionment shows a significant zonation of the source of PAHs: the civil coal pollution occurred in the north part, the local and far factory pollution happened in the middle area and the mixed pollution sources from coal and wood combustion, automotive emission, presented in the south area. The distribution of PAHs has a definite relationship with the sewage water flow and soil adsorption. The related coefficient between PAHs and physicochemical property showed there was a negative correlation between pH, silt, clay and PAHs while there was a positive correlation between total organic carbon, sand and PAHs. PMID- 25139036 TI - Designing systematic and center-specific metrics to foster innovation. PMID- 25139037 TI - Bladder volume estimation from electrical impedance tomography. AB - Non-invasive estimation of bladder volume is required to progress from scheduled voiding to a demand-driven emptying scheme for patients with impaired bladder volume sensation. Electrical impedance tomography (EIT) is a promising candidate for the non-invasive monitoring of bladder volume. This article focuses on four estimation algorithms used to map recorded EIT data to a volume estimate. Two different approaches are presented: the tomographic algorithms (one based on global impedance, the other on equivalent circular diameter) rely on the reconstruction of a tomographic image and then extract a volume estimate, whereas the parametric algorithms (one based on neural networks, the other on the singular value difference method) directly map the raw data to a volume estimate. The four algorithms presented here are evaluated for volume estimation error, noise tolerance and suppression of varying urine conductivity based on finite element simulation data. PMID- 25139035 TI - Distribution patterns of ammonia-oxidizing bacteria and anammox bacteria in the freshwater marsh of Honghe wetland in Northeast China. AB - Community characteristics of aerobic ammonia-oxidizing bacteria (AOB) and anaerobic ammonium-oxidizing (anammox) bacteria in Honghe freshwater marsh, a Ramsar-designated wetland in Northeast China, were analyzed in this study. Samples were collected from surface and low layers of sediments in the Experimental, Buffer, and Core Zones in the reserve. Community structures of AOB were investigated using both 16S rRNA and amoA (encoding for the alpha-subunit of the ammonia monooxygenase) genes. Majority of both 16S rRNA and amoA gene-PCR amplified sequences obtained from the samples in the three zones affiliated with Nitrosospira, which agreed with other wetland studies. A relatively high richness of beta-AOB amoA gene detected in the freshwater marsh might suggest minimal external pressure was experienced, providing a suitable habitat for beta-AOB communities. Anammox bacteria communities were assessed using both 16S rRNA and hzo (encoding for hydrazine oxidoreductase) genes. However, PCR amplification of the hzo gene in all samples failed, suggesting that the utilization of hzo biomarker for detecting anammox bacteria in freshwater marsh might have serious limitations. Results with 16S rRNA gene showed that Candidatus Kuenenia was detected in only the Experimental Zone, whereas Ca. Scalindua including different lineages was observed in both the Buffer and Experimental Zones but not the Core Zone. These results indicated that both AOB and anammox bacteria have specific distribution patterns in the ecosystem corresponding to the extent of anthropogenic impact. PMID- 25139039 TI - If groundwater is contaminated, will water from the well be contaminated? PMID- 25139038 TI - Balance of antiangiogenic and angiogenic factors in the context of the etiology of preeclampsia. AB - The "two-stage disorder" theory that is assumed for the etiology of preeclampsia hypothesizes that antiangiogenic and angiogenic factors and/or placental debris play an important role in this disorder. The physiological actions of placental debris occur via the balance between antiangiogenic and angiogenic factors. Accordingly, this balance between antiangiogenic and angiogenic factors should be investigated to elucidate the various pathological features of preeclampsia. Their accurate evaluation is needed to investigate not only antiangiogenic factors (such as sFlt-1 and sEng) and angiogenic factors (such as vascular endothelial growth factor, placental growth factor and transforming growth factor beta) but also the expression level of their receptors such as Flt-1 and Eng. However, it is ethically and technically difficult to investigate the above mentioned factors at antepartum in human patients. The examination of the ratios of sFlt-1/vascular endothelial growth factor receptor ligands and sEng/transforming vascular endothelial growth factor-beta and the use of experimental animal models may help in elucidating various unresolved issues in preeclampsia. PMID- 25139040 TI - Gender-specific associations of appendicular muscle mass with BMD in elderly Italian subjects. AB - Currently used diagnostic measures for sarcopenia are based on the evaluation of appendicular skeletal muscle mass (ASMM) divided by height-squared (ASMMI). This study aimed to investigate the associations between different operational definitions of appendicular muscle mass and BMD at different skeletal sites in aging Italian men and women. In 1199 consecutive healthy Italian subjects, aged 55 years or more (854 women, age 64.2 +/- 6.4 years and 165 men, age 65.3 +/- 6.1 years), we measured BMD at the lumbar spine (LS-BMD), at femoral neck (FN-BMD),at total hip (TH-BMD), at total body (WB-BMD) and at the right hand (H-BMD) and body composition parameters [ASMM, ASMMI, ASMM/Weight, total lean mass and total fat mass by DXA]. In all subjects, we also measured sex hormones, 25-hydroxyvitamin D and bone turnover markers. In men, both ASMM and ASMMI were positively correlated with BMD at all sites, whereas in women, ASMM and ASMMI did not show any significant correlation with BMD. In men, multiple regression analyses showed that ASMM was positively associated (p < 0.01) with FN-BMD, TH-BMD and H-BMD; however, these associations were no longer present when lean mass was included. In women, both fat mass and lean mass were found positively associated with BMD at all sites. In conclusion, among the different operational measures of the ASMM, only ASMM was significantly associated with BMD in elderly men, but not in elderly women. PMID- 25139043 TI - Dynamic NMR study of cyclic derivatives of pyridoxine. AB - A series of pyridoxine derivatives was investigated by (1) H and 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR. The free energies of activation for the pyridyl-oxygen rotation of the 2,4-dinitrophenyl ether of the seven membered acetals of pyridoxine were measured by dynamic NMR. A conformational exchange between the chair and twist forms of the seven-membered acetal ring was confirmed by dynamic NMR and STO3G computations. PMID- 25139042 TI - Burden of mental disorders and unmet needs among street homeless people in Addis Ababa, Ethiopia. AB - BACKGROUND: The impact of mental disorders among homeless people is likely to be substantial in low income countries because of underdeveloped social welfare and health systems. As a first step towards advocacy and provision of care, we conducted a study to determine the burden of psychotic disorders and associated unmet needs, as well as the prevalence of mental distress, suicidality, and alcohol use disorder among homeless people in Addis Ababa, the capital of Ethiopia. METHODS: A cross-sectional survey was conducted among street homeless adults. Trained community nurses screened for potential psychosis and administered standardized measures of mental distress, alcohol use disorder and suicidality. Psychiatric nurses then carried out confirmatory diagnostic interviews of psychosis and administered a locally adapted version of the Camberwell Assessment of Needs Short Appraisal Schedule. RESULTS: We assessed 217 street homeless adults, about 90% of whom had experienced some form of mental or alcohol use disorder: 41.0% had psychosis, 60.0% had hazardous or dependent alcohol use, and 14.8% reported attempting suicide in the previous month. Homeless people with psychosis had extensive unmet needs with 80% to 100% reporting unmet needs across 26 domains. Nearly 30% had physical disability (visual and sensory impairment and impaired mobility). Only 10.0% of those with psychosis had ever received treatment for their illness. Most had lived on the streets for over 2 years, and alcohol use disorder was positively associated with chronicity of homelessness. CONCLUSION: Psychoses and other mental and behavioural disorders affect most people who are street homeless in Addis Ababa. Any programme to improve the condition of homeless people should include treatment for mental and alcohol use disorders. The findings have significant implications for advocacy and intervention programmes, particularly in similar low income settings. PMID- 25139044 TI - Biomimetic nanostructuring of copper thin films enhances adhesion to the negative electrode laminate in lithium-ion batteries. AB - Thin films of copper are widely used as current collectors for the negative electrodes in lithium-ion batteries. However, a major cause of battery failure is delamination between the current collector and the graphite anode. When silicon or tin is used as active material, delamination becomes a key issue owing to the large volume changes of these materials during lithation and delithation processes. Learning from Nature, we developed a new biomimetic approach based on the adhesion properties of the feet of geckos. The biomimetic approach improves adhesion between the laminate and the copper surface by introducing an array of Cu(OH)2 nanorods, which increases the surface area of the current collector. When graphite anode laminate is casted onto regular and a modified copper surfaces, the modified current collector displays superior adhesion to graphite and the PVDF binder-based electrode. The electrochemical performance of the batteries using these electrodes is not compromised by the additional chemistry of the Cu(OH)2 on the copper surface. The technique can lead to enhanced battery lifetimes over long-term cycling. PMID- 25139045 TI - Cardiovascular disease risk is only elevated in hypertensive, formerly preeclamptic women. AB - OBJECTIVE: To analyse the predicted 10- and 30-year risk scores for cardiovascular disease (CVD) in patients who experienced preeclampsia (PE) 5-10 years previously compared with healthy parous controls. DESIGN: Observational study. SETTING: Tertiary referral hospital in the Netherlands. POPULATION: One hundred and fifteen patients with a history of PE and 50 controls. PE patients were categorised into two groups, hypertensive (n = 21) and normotensive (n = 94), based on use of antihypertensive medication, and next categorised into subgroups based on the onset of PE: early-onset PE (n = 39) and late-onset PE (n = 76). METHODS: All participants underwent cardiovascular risk screening 5-10 years after index pregnancy. We measured body mass, height and blood pressure. Blood was analysed for fasting glucose, insulin and lipid levels. All participants completed a validated questionnaire. The 10- and 30-year Framingham risk scores were calculated and compared. MAIN OUTCOME MEASURES: Estimated Framingham 10- and 30-year risk scores for CVD. RESULTS: The overall 10- and 30 year CVD median risks weighing subjects' lipids were comparable between formerly PE women and controls; 1.6 versus 1.5% (P = 0.22) and 9.0 versus 9.0% (P = 0.49), respectively. However, hypertensive formerly PE women have twice the CVD risk as normotensive formerly PE women: 10- and 30-year CVD median risks were 3.1 versus 1.5% (P < 0.01) and 19.0% versus 8.0% (P < 0.01), respectively. Risk estimates based on BMI rather than lipid profile show comparable results. Early-onset PE clustered more often in the hypertensive formerly PE group and showed significantly higher 10- and 30-year CVD risk estimates based on lipids compared with the late-onset PE group: 1.7 versus 1.3% (P < 0.05) and 10.0 versus 7.0% (P < 0.05), respectively. CONCLUSIONS: Women who are hypertensive after preeclampsia, have a twofold risk of developing CVD in the next 10-30 years. Formerly PE women who are normotensive in the first 10 years after their preeclamptic pregnancy have a comparable future cardiovascular risk to healthy controls. PMID- 25139046 TI - Diabetic foot: lipids, new and old vascular risk markers. PMID- 25139047 TI - Structure of the full-length insecticidal protein Cry1Ac reveals intriguing details of toxin packaging into in vivo formed crystals. AB - For almost half a century, the structure of the full-length Bacillus thuringiensis (Bt) insecticidal protein Cry1Ac has eluded researchers, since Bt derived crystals were first characterized in 1965. Having finally solved this structure we report intriguing details of the lattice-based interactions between the toxic core of the protein and the protoxin domains. The structure provides concrete evidence for the function of the protoxin as an enhancer of native crystal packing and stability. PMID- 25139048 TI - Detection of insulin granule exocytosis by an electrophysiology method with high temporal resolution reveals enlarged insulin granule pool in BIG3-knockout mice. AB - We recently identified BIG3 as a negative regulator of insulin granule biogenesis and reported increased insulin secretion in BIG3-knockout (BKO) mice. To pinpoint the site of action for BIG3, we investigated whether BIG3 regulates quantal insulin granule exocytosis. We established an assay to detect insulin granule exocytosis by recording ATP-elicited currents at high temporal resolution by patch clamp. Similarly to insulin, ATP release was increased in BKO beta-cells. Although the frequency of insulin granule exocytosis was increased in BKO beta cells, quantal size or release kinetics remained unchanged. Electron microscopy studies showed that the number of insulin granules was increased by >60% in BKO beta-cells. However, the number of morphologically docked granules was unaltered. The number of insulin granules having significant distances away from plasma membrane was greatly increased in BKO beta-cells. Thus, BIG3 negatively regulates insulin granule exocytosis by restricting insulin granule biogenesis without the release kinetics of individual granules at the final exocytotic steps being affected. Depletion of BIG3 leads to an enlarged releasable pool of insulin granules, which accounts for increased release frequency and consequently increased insulin secretion. PMID- 25139049 TI - Blood lipids affect rat islet blood flow regulation through beta3-adrenoceptors. AB - Pancreatic islet blood perfusion varies according to the needs for insulin secretion. We examined the effects of blood lipids on pancreatic islet blood flow in anesthetized rats. Acute administration of Intralipid to anesthetized rats increased both triglycerides and free fatty acids, associated with a simultaneous increase in total pancreatic and islet blood flow. A preceding abdominal vagotomy markedly potentiated this and led acutely to a 10-fold increase in islet blood flow associated with a similar increase in serum insulin concentrations. The islet blood flow and serum insulin response could be largely prevented by pretreatment with propranolol and the selective beta3-adrenergic inhibitor SR 59230A. The nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester prevented the blood flow increase but was less effective in reducing serum insulin. Increased islet blood flow after Intralipid administration was also seen in islet and whole pancreas transplanted rats, i.e., models with different degrees of chronic islet denervation, but the effect was not as pronounced. In isolated vascularly perfused single islets Intralipid dilated islet arterioles, but this was not affected by SR-59230A. Both the sympathetic and parasympathetic nervous system are important for the coordination of islet blood flow and insulin release during hyperlipidemia, with a previously unknown role for beta3 adrenoceptors. PMID- 25139052 TI - Vitamin D, asthma prevalence and asthma exacerbations: a large adult population based study. AB - BACKGROUND: The impact of low vitamin D status on asthma, asthma morbidity and control is unclear. We aimed to investigate in adults the associations between serum 25-hydroxyvitamin D level and prevalent asthma as well as asthma exacerbations. METHODS: A cohort of Israeli adults aged 22-50 years with documented vitamin D status were extracted from Clalit Health Services (HMO) between July 1, 2008 and July 1, 2012. Among this population, those with physician-diagnosed asthma and asthma exacerbations were identified. Asthma exacerbations were defined as any of the following: prescription for oral corticosteroids, >5 prescriptions for short acting beta agonists and more than four visits to a physician for asthma. Logistic regression models assessed the associations between vitamin D and both asthma and asthma exacerbations. RESULTS: Approximately 308 000 members with at least one vitamin D measurement were included in the cohort. Among them, 6.9% (21 237) had physician-diagnosed asthma vs 5.7% in the general population. Serum 25-OHD levels across both groups were similar. However, among those with vitamin D deficiency, the odds of having an exacerbation were 25% greater compared to those with levels in the normal range. This association remained significant after controlling for known confounders. CONCLUSION: While there was no significant association between vitamin D status and physician-diagnosed asthma, there was a strong association with asthma exacerbations. The presented evidence supports vitamin D screening in the subgroup of asthmatics that are uncontrolled and experience recurrent exacerbations. PMID- 25139051 TI - SUMOylation protects against IL-1beta-induced apoptosis in INS-1 832/13 cells and human islets. AB - Posttranslational modification by the small ubiquitin-like modifier (SUMO) peptides, known as SUMOylation, is reversed by the sentrin/SUMO-specific proteases (SENPs). While increased SUMOylation reduces beta-cell exocytosis, insulin secretion, and responsiveness to GLP-1, the impact of SUMOylation on islet cell survival is unknown. Mouse islets, INS-1 832/13 cells, or human islets were transduced with adenoviruses to increase either SENP1 or SUMO1 or were transfected with siRNA duplexes to knockdown SENP1. We examined insulin secretion, intracellular Ca2+ responses, induction of endoplasmic reticulum stress markers and inducible nitric oxide synthase (iNOS) expression, and apoptosis by TUNEL and caspase 3 cleavage. Surprisingly, upregulation of SENP1 reduces insulin secretion and impairs intracellular Ca2+ handling. This secretory dysfunction is due to SENP1-induced cell death. Indeed, the detrimental effect of SENP1 on secretory function is diminished when two mediators of beta-cell death, iNOS and NF-kappaB, are pharmacologically inhibited. Conversely, enhanced SUMOylation protects against IL-1beta-induced cell death. This is associated with reduced iNOS expression, cleavage of caspase 3, and nuclear translocation of NF kappaB. Taken together, these findings identify SUMO1 as a novel antiapoptotic protein in islets and demonstrate that reduced viability accounts for impaired islet function following SENP1 up-regulation. PMID- 25139053 TI - Karyotype evolution in the horseshoe bat Rhinolophus sedulus by whole-arm reciprocal translocation (WART). AB - Robertsonian (centric) fusion or fission is one of the predominant modes of chromosomal rearrangement in karyotype evolution among mammals. However, in karyotypes composed of only bi-armed chromosomes, creation of new chromosomal arm combinations in one step is possible only via whole-arm reciprocal translocation (WART). Although this type of rearrangement has often been proposed to play an important role in chromosomal evolution, direct observations of WARTs remained rare, and, in most cases, were found in hybrids of chromosomal races in the genera Mus and Sorex. For the first time, we present the karyotype of the horseshoe bat species Rhinolophus sedulus (2n = 28, FNa = 52), where a WART between 2 metacentric autosomes was detected by G-banding and confirmed by FISH with painting probes of the vespertilionid bat Myotis myotis. Among the 6 specimens analyzed, 2 showed the heterozygous condition of the WART, 1 showed the presumed ancestral, and 3 specimens showed the derived homozygous state. As the existence of a hybrid zone at the sampling locality is thought to be rather improbable, the WART may indicate ongoing karyotype evolution in this taxon. PMID- 25139050 TI - Loss of vitamin D receptor signaling from the mammary epithelium or adipose tissue alters pubertal glandular development. AB - Vitamin D3 receptor (VDR) signaling within the mammary gland regulates various postnatal stages of glandular development, including puberty, pregnancy, involution, and tumorigenesis. Previous studies have shown that vitamin D3 treatment induces cell-autonomous growth inhibition and differentiation of mammary epithelial cells in culture. Furthermore, mammary adipose tissue serves as a depot for vitamin D3 storage, and both epithelial cells and adipocytes are capable of bioactivating vitamin D3. Despite the pervasiveness of VDR in mammary tissue, individual contributions of epithelial cells and adipocytes, as well as the VDR-regulated cross-talk between these two cell types during pubertal mammary development, have yet to be investigated. To assess the cell-type specific effect of VDR signaling during pubertal mammary development, novel mouse models with mammary epithelial- or adipocyte-specific loss of VDR were generated. Interestingly, loss of VDR in either cellular compartment accelerated ductal morphogenesis with increased epithelial cell proliferation and decreased apoptosis within terminal end buds. Conversely, VDR signaling specifically in the mammary epithelium modulated hormone-induced alveolar growth, as ablation of VDR in this cell type resulted in precocious alveolar development. In examining cellular cross-talk ex vivo, we show that ligand-dependent VDR signaling in adipocytes significantly inhibits mammary epithelial cell growth in part through the vitamin D3-dependent production of the cytokine IL-6. Collectively, these studies delineate independent roles for vitamin D3-dependent VDR signaling in mammary adipocytes and epithelial cells in controlling pubertal mammary gland development. PMID- 25139054 TI - Pulmonary metastasis of giant cell tumor of bones. AB - Giant cell tumor of bone (GCTB) accounts for 5% of primary skeletal tumors. Although it is considered to be a benign lesion, there are still incidences of pulmonary metastasis. Pulmonary metastasis of GCTB may be affected by tumor grading and localization as well as the age, gender and overall health status of the patient. Patients with local recurrence are more likely to develop pulmonary metastasis of GCTB. High expression of some genes, cytokines and chemokines may also be closely related to the metastatic potential and prognosis of GCTB. The treatment of the primary GCTB is key to the final outcome of the disease, as intralesional curettage has a significantly higher local recurrence and pulmonary metastasis rate than wide resection. However, even patients with pulmonary metastasis seem to have a good prognosis after timely and appropriate surgical resection. It is hoped that with the development of novel surgical methods and drugs, pulmonary metastasis of GCTB can be prevented and treated more effectively. PMID- 25139055 TI - Effect of natural compounds on insulin signaling. AB - Results of several epidemiological studies have indicated that diabetes mellitus will become a global epidemic in the next decades, being more than 400 million the human subjects in the world affected by this disease in the 2030. Most of these subjects will be affected by type 2 diabetes mellitus (T2DM) whose diffusion is mainly related to excessive caloric upload, sedentary life and obesity. Typically, the treatment for T2DM is diet, weight control, physical activity or hypoglycaemic and/or lipid-lowering drugs. Unfortunately, these drugs often show low effectiveness or adverse side effects, thereby forcing patient to discontinue medical treatment. Nevertheless traditional medicine suggests the use of several formulations or medicinal foods to treat T2DM. Most of them are characterized by safety, low cost, effectiveness, and good availability. Before the advent of modern pharmacology, these remedies were used to treat diabetes and obesity or prevent their onset. Today, we know that their effectiveness is due to the presence of several bioactive compounds able to influence insulin signaling pathway and cellular metabolism. In the last decades, many efforts have been carried out to clarify their action mechanism. Here we provide a classification of the natural compounds that stimulate the insulin pathway, highlighting their effectiveness in controlling glycaemia on diabetic animal models or improving insulin signaling in cellular systems. PMID- 25139056 TI - Adjunctive graded body image exposure for eating disorders: A randomized controlled initial trial in clinical practice. AB - OBJECTIVE: Graded body image exposure is a key component of CBT for eating disorders (EDs). However, despite being a highly anxiety-provoking intervention, its specific effectiveness is unknown. The aims of this initial study were to investigate the feasibility and preliminary effectiveness of individualized graded body image exposure to a range of feared/avoided body image-related situations in a sample of partially remitted ED patients. METHOD: Forty-five female adult participants were randomly assigned to maintenance treatment as usual (MTAU) only or MTAU plus five sessions of graded body image exposure. RESULTS: The graded body image exposure intervention led to large improvements in body avoidance as measured by two different methods. In addition, there was evidence of a significant impact of body image exposure on the overvaluation of shape, but not weight, 5 months after treatment. DISCUSSION: Taken together, the current results provide evidence of the feasibility of adjunctive individualized graded body image exposure within a clinical treatment program and suggest that graded body image exposure reduces body avoidance behaviors in partially remitted ED patients. Our findings suggest that individualized graded body image exposure shows promise as an intervention targeting the overvaluation of shape in EDs. PMID- 25139058 TI - Impact of optical antennas on active optoelectronic devices. AB - Remarkable progress has been made in the fabrication and characterization of optical antennas that are integrated with optoelectronic devices. Herein, we describe the fundamental reasons for and experimental evidence of the dramatic improvements that can be achieved by enhancing the light-matter interaction via an optical antenna in both photon-emitting and -detecting devices. In addition, integration of optical antennas with optoelectronic devices can lead to the realization of highly compact multifunctional platforms for future integrated photonics, such as low-cost lab-on-chip systems. In this review paper, we further focus on the effect of optical antennas on the detectivity of infrared photodetectors. One particular finding is that the antenna can have a dual effect on the specific detectivity, while it can elevate light absorption efficiency of sub-wavelength detectors, it can potentially increase the noise of the detectors due to the enhanced spontaneous emission rate. In particular, we predict that the detectivity of interband photon detectors can be negatively affected by the presence of optical antennas across a wide wavelength region covering visible to long wavelength infrared bands. In contrast, the detectivity of intersubband detectors could be generally improved with a properly designed optical antenna. PMID- 25139059 TI - A review of the provision of appropriate advice by pharmacy staff for self medication in developing countries. AB - BACKGROUND: Patients in developing countries often prefer to self-medicate via community pharmacies. Pharmacy staff are therefore in a strategic position to optimize the health of the public by providing appropriate advice to patients who self-medicate. OBJECTIVE: To determine the proportion of pharmacy staff who provide appropriate advice when handling self-medication requests in developing countries. METHOD: A literature search was undertaken via MEDLINE, EMBASE, CINAHL Plus, Web of Science and International Pharmaceutical Abstracts. Studies that reported on the proportion of pharmacy staff providing appropriate advice when handling self-medication requests in developing countries were included. The appropriateness of advice was determined by each author's definition in the original studies. RESULTS: Twenty-eight studies met the inclusion criteria. There were variations in methods, scenarios, how the authors reported and defined appropriate advice, and study populations. The proportion of pharmacy staff providing appropriate advice varied widely from 0% to 96%, with a minority providing appropriate advice in 83% of the scenarios performed. CONCLUSION: There was considerable variation in results, with the majority of studies reporting that inappropriate advice was provided by pharmacy staff when handling self medication requests in developing countries. Consistent and robust methods are required to provide comparisons across practice settings. There is also a need to identify contributing factors to poor provision of advice for developing intervention strategies for practice improvement. PMID- 25139060 TI - The costs of hepatitis A infections in South Korea. AB - OBJECTIVES: The incidence of hepatitis A infections among young adults has recently increased in South Korea. Although universal vaccination has often been suggested to mitigate the problem, its rationale has not been well-understood. Estimating the societal costs of hepatitis A infections might support the development of intervention strategies. METHODS: We classified hepatitis A infections into eight clinical pathways and estimated the number of occurrences and cost per case for each clinical pathway using claim data from National Health Insurance and several national surveys as well as assumptions based on previous studies. To determine the total costs of a hepatitis A infection, both direct and indirect costs were estimated. Indirect costs were estimated using the human capital approach. All costs are adjusted to the year 2008. RESULTS: There were 30,240 identified cases of hepatitis A infections in 2008 for a total cost of 80,873 million won (2.7 million won per case). Direct and indirect costs constituted 56.2% and 43.8% of the total costs, respectively. People aged 20-39 accounted for 71.3% of total cases and 74.6% of total costs. Medical costs per capita were the lowest in the 0-4 age group and highest in the 20-29 age group. CONCLUSIONS: This study could provide evidence for development of cost-effective interventions to control hepatitis A infections. But the true costs including uncaptured and intangible costs of hepatitis A infections might be higher than our results indicate. PMID- 25139057 TI - A multilevel understanding of HIV/AIDS disease burden among African American women. AB - Disproportionate HIV/AIDS rates among African American women have been examined extensively, primarily from an individual-centered focus. Beyond individual behaviors, factors such as the hyperincarceration of African American men and geographically concentrated disadvantage may better explain inequitable disease burden. In this article I propose a conceptual model of individual, social, and structural factors that influence HIV transmission among African American women. The model can be used to develop comprehensive assessments and guide prevention programs in African American communities. PMID- 25139061 TI - Improvement to the scanning electron microscope image adaptive Canny optimization colorization by pseudo-mapping. AB - An improvement to the previously proposed adaptive Canny optimization technique for scanning electron microscope image colorization is reported. The additional feature, called pseudo-mapping technique, is that the grayscale markings are temporarily mapped to a set of pre-defined pseudo-color map as a mean to instill color information for grayscale colors in chrominance channels. This allows the presence of grayscale markings to be identified; hence optimization colorization of grayscale colors is made possible. This additional feature enhances the flexibility of scanning electron microscope image colorization by providing wider range of possible color enhancement. Furthermore, the nature of this technique also allows users to adjust the luminance intensities of selected region from the original image within certain extent. PMID- 25139062 TI - Homeostatic sleep pressure is the primary factor for activation of cortical nNOS/NK1 neurons. AB - Cortical interneurons, immunoreactive for neuronal nitric oxide synthase (nNOS) and the receptor NK1, express the functional activity marker Fos selectively during sleep. NREM sleep 'pressure' is hypothesized to accumulate during waking and to dissipate during sleep. We reported previously that the proportion of Fos(+) cortical nNOS/NK1 neurons is correlated with established electrophysiological markers of sleep pressure. As these markers covary with the amount of NREM sleep, it remained unclear whether cortical nNOS/NK1 neurons are activated to the same degree throughout NREM sleep or whether the extent of their activation is related to the sleep pressure that accrued during the prior waking period. To distinguish between these possibilities, we used hypnotic medications to control the amount of NREM sleep in rats while we varied prior wake duration and the resultant sleep pressure. Drug administration was preceded by 6 h of sleep deprivation (SD) ('high sleep pressure') or undisturbed conditions ('low sleep pressure'). We find that the proportion of Fos(+) cortical nNOS/NK1 neurons was minimal when sleep pressure was low, irrespective of the amount of time spent in NREM sleep. In contrast, a large proportion of cortical nNOS/NK1 neurons was Fos(+) when an equivalent amount of sleep was preceded by SD. We conclude that, although sleep is necessary for cortical nNOS/NK1 neuron activation, the proportion of cells activated is dependent upon prior wake duration. PMID- 25139063 TI - Dynamic interactions between plasma IL-1 family cytokines and central endogenous opioid neurotransmitter function in humans. AB - Evidence in animal models suggests IL-1 family cytokines interact with central endogenous opioid neurotransmitter systems, inducing or perpetuating pathological states such as persistent pain syndromes, depression, substance use disorders, and their comorbidity. Understanding these interactions in humans is particularly relevant to understanding pathological states wherein this neurotransmitter system is implicated (ie, persistent pain, mood disorders, substance use disorders, etc). Here, we examined relationships between IL-1beta, IL-1ra, and functional measures of the endogenous opioid system in 34 healthy volunteers, in the absence and presence of a standardized sustained muscular pain challenge, a psychophysical challenge with emotionally and physically stressful components. Mu opioid receptor availability in vivo was examined with [(11)C]carfentanil positron emission tomography (PET) scanning. Sex and neuroticism impacted IL-1 family cytokines; higher baseline IL-1beta and IL-1ra was identified in females with lower neuroticism. Higher baseline IL-1beta was also associated with reduced MU-opioid receptor availability (amygdala) and greater pain sensitivity. The pain challenge increased IL-1beta in females with high neuroticism. Strong associations between IL-1ra (an anti-nociceptive cytokine) and MU-opioid receptor activation (VP/NAcc) were identified during the pain challenge and the resulting analgesic effect of MU-opioid receptor activation was moderated by changes in IL 1beta whereby volunteers with greater pain induced increase in IL-1beta experienced less endogenous opioid analgesia. This study demonstrates the presence of relationships between inflammatory factors and a specific central neurotransmitter system and circuitry, of relevance to understanding interindividual variations in regulation of responses to pain and other physical and emotional stressors. PMID- 25139064 TI - Functional genetic variation of the cannabinoid receptor 1 and cannabis use interact on prefrontal connectivity and related working memory behavior. AB - Cannabinoid signaling is involved in different brain functions and it is mediated by the cannabinoid receptor 1 (CNR1), which is encoded by the CNR1 gene. Previous evidence suggests an association between cognition and cannabis use. The logical interaction between genetically determined cannabinoid signaling and cannabis use has not been determined. Therefore, we investigated whether CNR1 variation predicts CNR1 prefrontal mRNA expression in postmortem prefrontal human tissue. Then, we studied whether functional variation in CNR1 and cannabis exposure interact in modulating prefrontal function and related behavior during working memory processing. Thus, 208 healthy subjects (113 males) were genotyped for the relevant functional SNP and were evaluated for cannabis use by the Cannabis Experience Questionnaire. All individuals performed the 2-back working memory task during functional magnetic resonance imaging. CNR1 rs1406977 was associated with prefrontal mRNA and individuals carrying a G allele had reduced CNR1 prefrontal mRNA levels compared with AA subjects. Moreover, functional connectivity MRI demonstrated that G carriers who were also cannabis users had greater functional connectivity in the left ventrolateral prefrontal cortex and reduced working memory behavioral accuracy during the 2-back task compared with the other groups. Overall, our results indicate that the deleterious effects of cannabis use are more evident on a specific genetic background related to its receptor expression. PMID- 25139065 TI - Hypoactivation of the ventral and dorsal striatum during reward and loss anticipation in antipsychotic and mood stabilizer-naive bipolar disorder. AB - Increased activity within known reward-processing neurocircuitry (eg, ventral striatum, VS) has been reported among medicated individuals with bipolar disorder (BD) I and II. However, such findings are confounded by the potential ameliorative effects of mood-stabilizing and antipsychotic medications on neural activations. This study tests the hypothesis that a pathophysiological locus of alterations in reward processing is present within the striatum in antipsychotic and lithium-naive individuals with BD. Twenty antipsychotic and lithium-naive individuals with BD II or BD not-otherwise specified (NOS) and 20 matched healthy comparison individuals participated in functional magnetic resonance imaging during the performance of a monetary incentive delay task. Between-group comparisons were conducted using small-volume correction focusing on orthogonal a priori regions of interest centered in the VS and dorsal striatum (DS), respectively. During reward anticipation, unmedicated individuals with BD II/NOS had decreased activity within the DS (but not VS). During loss anticipation, on the other hand, decreased activation within both the VS and DS was observed. Across all participants, DS activity (during reward anticipation) was positively associated with putamen volume. This is the first report of decreased dorsal and ventral striatal activity among unmedicated individuals with BD II/NOS. These data contradict a simple 'reward hypersensitivity' model of BD, and add to a growing body of literature suggesting that blunted reward processing may be a vulnerability factor for both mood- and addiction-related disorders. PMID- 25139066 TI - Chemoenzymatic synthesis of trehalose analogues: rapid access to chemical probes for investigating mycobacteria. AB - Trehalose analogues are emerging as valuable tools for investigating Mycobacterium tuberculosis, but progress in this area is slow due to the difficulty in synthesizing these compounds. Here, we report a chemoenzymatic synthesis of trehalose analogues that employs the heat-stable enzyme trehalose synthase (TreT) from the hyperthermophile Thermoproteus tenax. By using TreT, various trehalose analogues were prepared quickly (1 h) in high yield (up to >99 % by HPLC) in a single step from readily available glucose analogues. To demonstrate the utility of this method in mycobacteria research, we performed a simple "one-pot metabolic labeling" experiment that accomplished probe synthesis, metabolic labeling, and imaging of M. smegmatis in a single day with only TreT and commercially available materials. PMID- 25139067 TI - Liver resection for colorectal metastases: results and prognostic factors with 10 year follow-up. AB - PURPOSE: Actual 5-year survival rates after resection of colorectal liver metastases (CLM) are 25-45%, whereas 10-year survival rates are extrapolated from survival curves. Few studies have reported long-term survivors with 10 years of actual follow-up. Therefore, no recurrences occurring after 10-plus years have been reported. The aim of our study was to analyze actual 10-year survival rates and prognostic factors. METHODS: Clinical data of patients with CLM who had undergone first liver resection in our center between January 1990 and December 2000 were retrospectively analyzed. RESULTS: Eighty-nine patients of mean age 64 years were studied. Three patients were excluded from the study: one because of postoperative death, and two from being lost to follow-up. All other subjects had a potential 10-year follow-up. Only 33% patients received perioperative chemotherapy. The actual 10-year overall and disease-free survival rate were 22 and 19%, respectively. Poor prognostic factors were disease-free interval less than 1 year, wedge liver resection, clinical risk score>2, segment 1 CLM location, and peritumoral lymphangitis. Good prognostic factors were tumors having mucinous components in primary tumor and CLM located in the right lobe. CONCLUSIONS: With actual long-term follow-up for 10 years, disease-free survival rate is 19% and mainly depends on surgical management. Recurrence continues to occur more than 5 years after liver resection for CLM; cure cannot be assumed at this time. Clinical risk score is a good predictor of cure and should be taken into account when choosing perioperative treatment. PMID- 25139068 TI - Development of a dynamic model for ventral hernia mesh repair. AB - INTRODUCTION: The adequate way of mesh fixation in laparoscopic ventral hernia repair is still subject to debate. So far, simulation has only been carried out in a static way, thereby omitting dynamic effects of coughing or vomiting. We developed a dynamic model of the anterior abdominal wall. MATERIALS AND METHODS: An aluminium cylinder was equipped with a pressure controlled, fluid-filled plastic bag, simulating the abdominal viscera. A computer-controlled system allowed the control of influx and efflux, thus creating pressure peaks of up to 200 mmHg to simulate coughing and 290 mmHg to simulate vomiting. We tested fixation with tacks (Absorbatack, Covidien Deutschland, Neustadt a. D., Germany). The model was controlled for the friction coefficient of the tissue against the mesh and the physiologic elasticity of the abdominal wall surrogate. RESULTS: The model was able to create pressure peaks equivalent to physiologic coughs or vomiting. Physiologic elasticity was thereby maintained. We could show that the friction coefficient is crucial to achieve a physiologic situation. The meshes showed a tendency to dislocate with an increasing number of coughs (Fig. 4). Nevertheless, when applied in a plain manner, the meshes withstood more cough cycles than when applied with a bulge as in laparoscopic surgery. CONCLUSIONS: The dynamic movement of the abdominal wall, the friction between tissue and mesh and the way of mesh application are crucial factors that have to be controlled for in simulation of ventral abdominal hernia closure. We could demonstrate that patient specific factors such as the frequency of coughing as well as the application technique influence the long term stability of the mesh. PMID- 25139069 TI - The Charlson comorbidity index predicts survival after disease recurrence in patients following radical cystectomy for urothelial carcinoma of the bladder. AB - OBJECTIVE: To identify prognostic clinical and histopathological parameters, including comorbidity indices at the time of radical cystectomy (RC), for overall survival (OS) after recurrence following RC for urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: A retrospective multicenter study was carried out in 555 unselected consecutive patients who underwent RC with pelvic lymph node dissection for UCB from 2000 to 2010. A total of 227 patients with recurrence comprised our study group. Cox proportional hazards regression models were calculated with established variables to assess their independent influence on OS after recurrence. RESULTS: The median time from RC to recurrence and the median OS after recurrence was 10.9 and 5.4 months, respectively. Neither the time to recurrence nor the type of recurrence (systematic vs. local) was predictive of the OS. In contrast, age (hazard ratio (HR) 1.53, p = 0.011), lymph node metastasis (HR 1.56, p = 0.007), and positive surgical margins (HR 1.53, p = 0.046) significantly affected the OS after disease recurrence. In addition, the dichotomized Charlson comorbidity index (CCI; dichotomized into >2 vs. 0-2) was the only comorbidity score with an independent prediction of OS (HR 1.41, p = 0.033). We observed a significant gain in the base model's predictive accuracy, i.e. from 68.4 to 70.3% (p < 0.001), after inclusion of the dichotomized CCI. CONCLUSIONS: We present the first outcome study of comorbidity indices used as predictors of OS after disease recurrence in patients undergoing RC for UCB. The CCI at the time of RC had no significant influence on the time to recurrence but represented an independent predictor of OS after disease recurrence. PMID- 25139070 TI - Assessment of mass transfer and mixing in rigid lab-scale disposable bioreactors at low power input levels. AB - Mass transfer, mixing times and power consumption were measured in rigid disposable stirred tank bioreactors and compared to those of a traditional glass bioreactor. The volumetric mass transfer coefficient and mixing times are usually determined at high agitation speeds in combination with sparged aeration as used for single cell suspension and most bacterial cultures. In contrast, here low agitation speeds combined with headspace aeration were applied. These settings are generally used for cultivation of mammalian cells growing adherent to microcarriers. The rigid disposable vessels showed similar engineering characteristics compared to a traditional glass bioreactor. On the basis of the presented results appropriate settings for adherent cell culture, normally operated at a maximum power input level of 5 W m(-3) , can be selected. Depending on the disposable bioreactor used, a stirrer speed ranging from 38 to 147 rpm will result in such a power input of 5 W m(-3) . This power input will mix the fluid to a degree of 95% in 22 +/- 1 s and produce a volumetric mass transfer coefficient of 0.46 +/- 0.07 h(-1) . PMID- 25139071 TI - Surface plasmon enhanced photochemical etching of p-type GaP: a direct demonstration of wavelength selectivity. AB - We report here on significant enhancement of the photochemical etching of p-type gallium phosphide (GaP) by Au plasmonic nanostructures. The photochemical etching rate of defect (dislocation) states of Au-coated p-GaP samples is ten times higher than blank samples when irradiated with 532 nm laser. It is confirmed that the enhancement of photochemical etching is wavelength selective. Only 532 nm laser can efficiently increase the photochemical etching rate, while lasers of other wavelengths (375, 405, 445, and 473 nm) show limited or negative effects. This observation can be attributed to defect (dislocation) enhanced photochemical etching through localized surface plasmon resonance of Au nanostructures. This method may open a new pathway for controlled fabrication of novel optoelectronic devices. PMID- 25139073 TI - Injectional anthrax - new presentation of an old disease. AB - Bacillus anthracis infection (anthrax) has three distinct clinical presentations depending on the route of exposure: cutaneous, gastrointestinal and inhalational anthrax. Each of these can lead to secondary bacteraemia and anthrax meningitis. Since 2009,anthrax has emerged among heroin users in Europe,presenting a novel clinical manifestation, 'injectional anthrax', which has been attributed to contaminated heroin distributed throughout Europe; before 2009 only one case was reported. During 2012 and 2013,new cases of injectional anthrax were diagnosed in Denmark, France, Germany, and the United Kingdom.Here we present a comprehensive review of the literature and information derived from different reporting systems until 31 December 2013. Overall 70 confirmed cases were reported, with 26 fatalities (37% case fatality rate).The latest two confirmed cases occurred in March 2013. Thirteen case reports have been published,describing 18 confirmed cases. Sixteen of these presented as a severe soft tissue infection that differed clinically from cutaneous anthrax, lacked the characteristic epidemiological history of animal contact and ten cases required complimentary surgical debridement. These unfamiliar characteristics have led to delays of three to 12 days in diagnosis, inadequate treatment and a high fatality rate. Clinicians' awareness of this recently described clinical entity is key for early 'and successful management of patients. PMID- 25139072 TI - Psychometric Properties of Two Brief Versions of the Voices Acceptance and Action Scale (VAAS): Implications for the Second-wave and Third-wave Behavioural and Cognitive Approaches to Auditory Hallucinations. AB - Despite a steep rise in the evidence base for third-wave cognitive and behavioural therapy approaches over the past decade, a scarcity of change measures relevant to these therapies as applied to psychosis is arguably slowing empirical progress in the area. The Voices Acceptance and Action Scale (VAAS), a measure of acceptance of voice experiences, is a notable exception. However, there are no published data on its psychometric properties outside of that provided by the scale developers. The current study explored the psychometric properties of two brief versions of the VAAS in a sample of psychotic voice hearers in a routine outpatient mental health service. Evidence from the current study suggests that both brief versions are robust measures of acceptance of voice experiences. Some limited support for the shortened VAAS-9 as being a marginally improved scale over the original brief VAAS-12 was also found. The current study found acceptance of voices to be highly related to depression, anxiety, stress and general negative affect and to predict unique variance in depression and general negative affect beyond that attributable to negative beliefs about voices and thought suppression. It was also found that acceptance was positively related to the use of reappraisal, indicating that the distinctiveness of acceptance from appraisal processes may be less pronounced in this context than what was has been reported previously. Implications for future research, as well as the practice of second-wave and third-wave cognitive and behavioural approaches to psychosis, are discussed. KEY PRACTITIONER MESSAGE: Two brief versions of the VAAS instrument were found to be robust measures of acceptance of psychotic voice experiences. The construct of acceptance of voices is highly related to indices of well-being and negative appraisal processes in psychosis and appears to offer an alternative route to therapeutically addressing the toxic effects of negative beliefs about voices. The recent focus on acceptance-based techniques within cognitive and behavioural approaches to psychosis was supported. PMID- 25139074 TI - Increase of pertussis incidence in 2010 to 2012 after 12 years of low circulation in Spain. AB - In Spain, whole cell pertussis vaccination started in 1975, with three doses before the age of 6-7 months. Doses at 15-18 months and 4-6 years were introduced in 1996 and 2001, respectively. Spain switched to an acellular vaccine in 2005. From 1998 to 2009, pertussis incidence rates remained <=1.5 cases/100,000 inhabitants but increased from 2010 to 7.5 cases/100,000 in 2012. Data from 1998 to 2012 were analysed to assess disease trends and susceptible populations. We defined four epidemic periods: 1998-2001 (reference), 2002-05, 2006-09 and 2010 12. In 2002-05, the incidence rate increased in individuals aged 15-49 years (IRR: 1.41 (95% CI: 1.11-1.78)) and >=50 years (IRR: 2.78 (95% CI: 1.78-4.33)) and in 2006-09 increased also in infants aged <3 months (IRR: 1.83 (95% CI: 1.60 2.09)). In 2010-12, the incidence rate increased notably in all age groups, with IRRs ranging between 2.5 (95% CI: 2.3-2.8) in 5-9 year-olds and 36.0 (95% CI: 19.4-66.8) in 20-29 year-olds. These results, consistent with the country's vaccination history, suggest a progressive accumulation of susceptible individuals due to waning immunity after years of low incidence. Further vaccination strategies should be assessed and implemented to prevent pertussis in pre-vaccinated infants, in whom the disease is more severe. PMID- 25139075 TI - Potential association between the recent increase in campylobacteriosis incidence in the Netherlands and proton-pump inhibitor use - an ecological study. AB - The Netherlands saw an unexplained increase in campylobacteriosis incidence between 2003 and 2011, following a period of continuous decrease. We conducted an ecological study and found a statistical association between campylobacteriosis incidence and the annual number of prescriptions for proton pump inhibitors (PPIs), controlling for the patient's age, fresh and frozen chicken purchases (with or without correction for campylobacter prevalence in fresh poultry meat). The effect of PPIs was larger in the young than in the elderly. However, the counterfactual population-attributable fraction for PPIs was largest for the elderly (ca 45% in 2011) and increased at population level from 8% in 2004 to 27% in 2011. Using the regression model and updated covariate values, we predicted a trend break for 2012, largely due to a decreased number of PPI prescriptions, that was subsequently confirmed by surveillance data. Although causality was not shown, the biological mechanism, age effect and trend-break prediction suggest a substantial impact of PPI use on campylobacteriosis incidence in the Netherlands. We chose the ecological study design to pilot whether it is worthwhile to further pursue the effect of PPI on campylobacteriosis and other gastrointestinal pathogens in prospective cohort studies. We now provide strong arguments to do so. PMID- 25139076 TI - The hanta hunting study: underdiagnosis of Puumala hantavirus infections in symptomatic non-travelling leptospirosis-suspected patients in the Netherlands, in 2010 and April to November 2011. AB - Leptospirosis and haemorrhagic fever with renal syndrome (HFRS) are hard to distinguish clinically since these two important rodent-borne zoonoses share hallmark symptoms such as renal failure and haemorrhage. Leptospirosis is caused by infection with a spirochete while HFRS is the result of an infection with certain hantaviruses. Both diseases are relatively rare in the Netherlands. Increased incidence of HFRS has been observed since 2007 in countries that border the Netherlands. Since a similar rise in incidence has not been registered in the Netherlands, we hypothesise that due to overlapping clinical manifestations, hantavirus infections may be confused with leptospirosis, leading to underdiagnosis. Therefore, we tested a cohort of non-travelling Dutch patients with symptoms compatible with leptospirosis, but with a negative diagnosis, during 2010 and from April to November 2011. Sera were screened with pan hantavirus IgG and IgM enzyme-linked immunosorbent assays (ELISAs). Sera with IgM reactivity were tested by immunofluorescence assay (IFA). ELISA (IgM positive) and IFA results were confirmed using focus reduction neutralisation tests (FRNTs). We found hantavirus-specific IgG and/or IgM antibodies in 4.3% (11/255) of samples taken in 2010 and in 4.1% (6/146) of the samples during the 2011 period. After FRNT confirmation, seven patients were classed as having acute Puumala virus infections. A review of hantavirus diagnostic requests revealed that at least three of the seven confirmed acute cases as well as seven probable acute cases of hantavirus infection were missed in the Netherlands during the study period. PMID- 25139077 TI - WHO publishes handbook on the analysis of TB surveillance data. PMID- 25139080 TI - CRPS-related neurogenic edema responsive to dextromethorphan/quinidine. PMID- 25139079 TI - Phosphonated near-infrared fluorophores for biomedical imaging of bone. AB - The conventional method for creating targeted contrast agents is to conjugate separate targeting and fluorophore domains. A new strategy is based on the incorporation of targeting moieties into the non-delocalized structure of pentamethine and heptamethine indocyanines. Using the known affinity of phosphonates for bone minerals in a model system, two families of bifunctional molecules that target bone without requiring a traditional bisphosphonate are synthesized. With peak fluorescence emissions at approximately 700 or 800 nm, these molecules can be used for fluorescence-assisted resection and exploration (FLARE) dual-channel imaging. Longitudinal FLARE studies in mice demonstrate that phosphonated near-infrared fluorophores remain stable in bone for over five weeks, and histological analysis confirms their incorporation into the bone matrix. Taken together, a new strategy for creating ultra-compact, targeted near infrared fluorophores for various bioimaging applications is described. PMID- 25139081 TI - Kinetics of primary bile acids in patients after proctocolectomy and ileal pouch anal anastomosis. AB - BACKGROUND: The high incidence of cholesterol gallstones in patients after proctocolectomy with ileal pouch-anal anastomosis (IPAA) may be due to an increased loss of bile acids. We aimed to evaluate the kinetics of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) in these patients. METHODS: Pool sizes, synthesis rates, and fractional turnover rates of CA and CDCA were determined by combined capillary gas chromatography/isotope ratio mass spectrometry in serum samples after administration of [13C]CA and [13C]CDCA in 6 patients and 9 healthy volunteers. RESULTS: In patients with IPAA, pool sizes of CA and CDCA were 11.5 (8.2-23.8) and 12.1 (6.7-20.1) umol/kg, respectively, and were significantly lower than in healthy controls [36.0 (24-47) and 29.0 (21-42) umol/kg, respectively; p < 0.05, each]. Fractional turnover rates of CA [1.19 (1.06-1.82) vs. 0.31 (0.13-0.54) per day] and CDCA [1.01 (0.50-1.63) vs. 0.23 (0.09-0.36) per day] were increased fourfold in patients with IPAA (p < 0.05, each). Synthesis rates of CDCA [10.2 (5.2-32.9) vs. 6.6 (2.7-10.5) umol/kg per day, p = 0.05] and CA [15.1 (9.3-39.4) vs. 11.5 (3.1-20.5) umol/kg per day, n.s.] tended to be higher in patients with IPAA than in controls. CONCLUSION: The reduced pool size of primary bile acids may contribute to the high incidence of cholesterol gallstones in patients after proctocolectomy and IPAA. PMID- 25139082 TI - Azithromycin hydrates-implications of processing-induced phase transformations. AB - According to label claims, in commercial solid dosage forms, azithromycin (AZI) exists either as a monohydrate (MH) or as a dihydrate (DH). Although these two forms are known to be relatively stable in the solid state, AZI sesquihydrate (SH) was observed in a drug product. This was believed to be a consequence of a processing-induced phase transformation. Our goal was to prepare and characterize AZI SH and map its solid-state transition pathways with other AZI phases. When dehydrated at temperatures <80 degrees C, DH yielded an isomorphic dehydrate, whereas dehydration at >=80 degrees C yielded SH. Heating SH to 100 degrees C or holding at 0% RH at room temperature, yielded an amorphous product through an intermediate isomorphic dehydrate, isostructural to SH. On the other hand, dehydration of MH (at >=60 degrees C) resulted in amorphization with no intermediate crystalline anhydrate. Diagnostic XRD peaks of AH, MH, SH, and DH enabled their unambiguous identification. However, the presence of crystalline excipients hindered active pharmaceutical ingredient characterization in drug product. Pattern subtraction method was used to selectively remove the contribution of the crystalline excipients to the overall diffraction pattern, thereby facilitating the physical characterization of AZI in the drug product. PMID- 25139083 TI - Controlling radiation exposure in interventional cardiology. PMID- 25139084 TI - Noncardiac surgery after coronary revascularization: more contemporary evidence needed. PMID- 25139085 TI - Reconciling poststenotic pressure with hyperemic flow: comparing coronary flow reserve, instantaneous wave-free ratio, and fractional flow reserve. PMID- 25139086 TI - Torrent of troponin. PMID- 25139087 TI - How to move toward the least invasive transfemoral transcatheter aortic valve implantation procedure? PMID- 25139088 TI - Mechanisms by which transradial approach may reduce mortality in ST-segment elevation myocardial infarction. PMID- 25139089 TI - Delayed and fatal embolization of a left atrial appendage closure device. PMID- 25139090 TI - Unanticipated pseudocoarctation highlights the importance of visualizing aortic arch anatomy before transfemoral transcatheter aortic valve implantation. PMID- 25139091 TI - Response to letter regarding, "administration of a loading dose has no additive effect on platelet aggregation during the switch from ongoing clopidogrel treatment to ticagrelor in patients with acute coronary syndrome". PMID- 25139093 TI - Identification of miRNAs as potential new biomarkers for nervous system cancer. AB - Several recent studies have indicated the possibility of detecting dysregulated microRNAs (miRNAs) to diagnose nervous system cancer (NSC). Our study was conducted to explore the clinical applicability of miRNAs as potential ideal biomarkers for the diagnosis of NSC. For this meta-analysis, a systematic literature search was conducted in the Embase, Medline, Cochrane, Wangfang, and Sinomed databases. A standard quality tool-quality assessment of diagnostic accuracy studies was employed to assess the quality of the included studies. Specificity, sensitivity, diagnostic odds ratio (DOR), and area under curve (AUC) were pooled to assess overall test accuracy. In total, 25 studies from 7 articles, including 388 patients with NSC and 435 controls (healthy controls and patients with neurologic disorders), were included in this meta-analysis. For the studied miRNAs, the pooled sensitivity, specificity, and DOR for predicting NSC were 85% (95% confidence interval [CI] 80-89%), 85% (95% CI 80-89%), and 32 (95% CI 19-55), respectively. The pooled AUC for miRNAs identifying NSC was 0.92. In addition, results from subgroup analyses indicated that using miRNA panels yield a much better diagnostic accuracy when compared with using a particular miRNA. The current evidence suggests that miRNAs, especially miRNA panels on body fluids, may be suitable for use as diagnostic biomarkers for NSC patients. However, more prospective studies using larger cohorts should be conducted to confirm their degree of accuracy. PMID- 25139094 TI - Reduction of alpha-dystroglycan expression is correlated with poor prognosis in glioma. AB - Dystroglycan (DG), a multifunctional protein dimer of non-covalently linked alpha and beta subunits, is best known as an adhesion and transduction molecule linking the cytoskeleton and intracellular signaling pathways to extracellular matrix proteins. Loss of DG binding, possibly by degradation or disturbed glycosylation, has been reported in a variety of cancers. DG is abundant at astroglial endfeet forming the blood-brain barrier (BBB) and glia limitans; so, we examined if loss of expression is associated with glioma. Expression levels of alpha-DG and beta DG were assessed by immunohistochemistry in a series of 78 glioma specimens to determine the relationship with tumor grade and possible prognostic significance. alpha-DG immunostaining was undetectable in 44 of 49 high-grade specimens (89.8%) compared to 15 of 29 low-grade specimens (51.72%) (P<0.05). Moreover, loss of alpha-DG expression was an independent predictor of shorter disease-free survival (DFS) (hazards ratio (HR) = 0.142, 95% confidence interval (CI) 0.033-0.611, P=0.0088). Reduced expression of both alpha-DG and beta-DG was also a powerful negative prognostic factor for DFS (HR=2.556, 95% CI 1.403-4.654, P=0.0022) and overall survival (OS) (HR=2.193, 95% CI 1.031-4.666, P=0.0414). Lack of alpha-DG immunoreactivity is more frequent in high-grade glioma and is an independent predictor of poor clinical outcome. Similarly, lack of both alpha-DG and beta-DG immunoreactivity is a strong independent predictor of clinical outcome. PMID- 25139095 TI - Collagen triple helix repeat containing 1 (Cthrc1) is an independently prognostic biomarker of non-small cell lung cancers with cigarette smoke. AB - Collagen triple helix repeat containing 1 (Cthrc1) has been recently documented in various malignancies, but its role in non-small cell lung cancer (NSCLC) remains uncertain. In the current study, we investigated the level of Cthrc1 in NSCLC tissues by immunohistochemistry. Results revealed that Cthrc1 overexpression was significantly associated with differentiation (P=0.039), tumor node-metastasis (TNM) stage (P=0.035), lymph node status (P=0.001), and cigarette smoke (P=0.037). Furthermore, it was shown that patients with high Cthrc1 expression had significantly poorer overall survival (OS) and disease-free survival (DFS; P=0.004 and P=0.010, respectively). Interestingly, high Cthrc1 expression was an independent prognostic factor for both OS and DFS (P=0.010 and P=0.005, respectively) only in NSCLCs with cigarette smoke. These results indicated and suggested that Cthrc1 could be used as a prognostic marker for NSCLC, and it may play an important role in the smoked-related NSCLC. PMID- 25139096 TI - Primary epidural hemangiopericytoma in the sacrum: a rare case and literature review. AB - Hemangiopericytoma (HPC) is an uncommon highly vascular neoplasm that originated from Zimmerman's pericytes which surrounds the endothelial tissue. Primary epidural HPC of the sacrum is extremely rare. We reported an unusual case of primary epidural malignant HPC of the sacrum that invaded vertebral bone and caused rectum compression in a 57-year-old male for the first time. The patient presented progressive low back pain and ribbon-like stool over 3 months. The surgical intervention involved sacrectomy and en bloc resection of the tumor. We described the clinical, radiological, and histological features of this tumor and reviewed the literature. PMID- 25139092 TI - Regulation of male sex determination: genital ridge formation and Sry activation in mice. AB - Sex determination is essential for the sexual reproduction to generate the next generation by the formation of functional male or female gametes. In mammals, primary sex determination is commenced by the presence or absence of the Y chromosome, which controls the fate of the gonadal primordium. The somatic precursor of gonads, the genital ridge is formed at the mid-gestation stage and gives rise to one of two organs, a testis or an ovary. The fate of the genital ridge, which is governed by the differentiation of somatic cells into Sertoli cells in the testes or granulosa cells in the ovaries, further determines the sex of an individual and their germ cells. Mutation studies in human patients with disorders of sex development and mouse models have revealed factors that are involved in mammalian sex determination. In most of mammals, a single genetic trigger, the Y-linked gene Sry (sex determination region on Y chromosome), regulates testicular differentiation. Despite identification of Sry in 1990, precise mechanisms underlying the sex determination of bipotential genital ridges are still largely unknown. Here, we review the recent progress that has provided new insights into the mechanisms underlying genital ridge formation as well as the regulation of Sry expression and its functions in male sex determination of mice. PMID- 25139098 TI - Lymph node ratio as an independent prognostic indicator in stage III colorectal cancer: especially for fewer than 12 lymph nodes examined. AB - Although nodal invasion represents one of the most powerful prognostic indicators in colorectal cancer (CRC), marked heterogeneity exists within stage III patients. Lymph node ratio (LNR) may offer more precise prognostication in stage III CRC. The aim of this study is to investigate the prognostic impact of LNR on survival in stage III CRC patients. We retrospectively reviewed the data of 288 consecutive patients who underwent radical resection for stage III CRC between January 2000 and December 2008 in the Gastrointestinal Surgery Department, Peking University People's Hospital. The patients were divided into three groups according to LNR quartiles: LNR < 0.167 (n=72), 0.167 <= LNR < 0.562 (n = 140), and LNR >= 0.562 (n=76). The association between overall survival (OS) and disease-free survival (DFS) and 11 variables including age, gender, tumor location, size, grade, histology, tumor (T) stage, number of metastatic LNs, and LNR was analyzed by multivariate analysis. Survival curves were plotted by the Kaplan-Meier method. Both LNR and the number of metastatic LNs were significant prognostic factors for 5-year DFS and OS in stage III CRC patients. LNR was an independent prognostic factor for 5-year OS. LNR remained an independent prognostic factor in patients with fewer than 12 lymph nodes examined. LNR was a potent independent prognostic predictor for OS and DFS in stage III CRC patients, especially for patients with fewer than 12 lymph nodes examined. PMID- 25139099 TI - Prognostic role of microRNA-31 in various cancers: a meta-analysis. AB - To date, many studies have shown that microRNAs (miRNA) exhibit altered expression levels in various cancers and may play a potential role as diagnostic and prognostic biomarkers of cancers. This meta-analysis was designed to evaluate the exact role of microRNA-31 (miR-31) for survival and discuss the possibility of utilizing miR-31 to predict the prognosis of patients with various human cancers. Electronic literature databases including PubMed, Web of Science, and Embase were searched for articles published until May 2014. The articles only written in English were considered. Data were extracted from studies comparing overall survival (OS), cancer-specific survival (CSS), or postoperative survival (PS) in patients with multiple cancers, which showed higher miR-31 expression than with similar patients. Pooled hazard ratios (HRs) of miR-31 for survival and 95 % confidence intervals (CI) were calculated. Ten studies with a total of 1,648 participants were included for the meta-analysis. For OS, the pooled HRs of higher miR-31 expression in cancers indicated significant predictor poorer survival in general cancers in either univariate analysis (HR=2.34, 95 % CI=1.15 3.52, P<0.05) or multivariate analysis (HR=1.15, 95 % CI=1.04-1.26, P<0.05). For CSS, elevated miR-31 was also a significant predictor to general cancers in multivariate analysis (HR=1.77, 95 % CI=1.06-2.47, P<0.05). And, no association was found between miR-31 expression and PS. In conclusion, the present findings indicate that high miR-31 expression is associated with poor OS and CSS in patients with general cancers and miR-31 may be a useful clinical prognostic biomarker. PMID- 25139097 TI - Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and prognosis of esophageal cancer patients in northern Indian population. AB - Recent genome-wide association studies (GWAS) have identified variants in phospholipase C epsilon1 (PLCE1) as novel susceptibility markers for esophageal squamous cell carcinoma (ESCC) in Chinese population. Although few studies have replicated this findings in other populations, but results are contradictory. So, we aimed to replicate association of two previously reported non-synonymous polymorphisms (rs2274223A>G and rs3765524C>T) from haplotype block 10 and evaluated a novel variant (rs7922612C>T) from haplotype block 2 of PLCE1 with susceptibility and prognosis of ESCC in northern Indian population. The genotyping of PLCE1 variants were performed in 293 histopathologically confirmed incident ESCC cases (including 177 follow-up cases) and 314 age-, gender-, and ethnicity-matched controls using PCR RFLP. All statistical analyses were performed through SPSS version 15.0. Modeling and functional prediction of two non-synonymous variants were carried out using bioinformatics tools. PLCE1 polymorphisms were not associated with susceptibility to ESCC or its clinical phenotypes (tumor location/lymph node metastasis). No interaction with environmental risk factors was found. In silico analysis suggested negligible effect on structure of PLCE1 protein due to PLCE1 rs2274223 (H1927R) and rs3765524 (T1777I) polymorphisms. Survival analysis showed PLCE1 rs7922612CT + TT genotype conferred adverse outcome to ESCC patients. Our study for the first time suggests that GWAS originated PLCE1 variants do not have independent role in susceptibility of ESCC in northern Indian population; however, a novel haplo tagging SNP rs7922612 may modify survival outcome of ESCC patients. PMID- 25139100 TI - Glycolytic activity with 18F-FDG PET/CT predicts final neoadjuvant chemotherapy response in breast cancer. AB - The purpose of the present study is to explore the relation between glycolytic metabolism assessed by (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and final neoadjuvant chemotherapy (NC) response in locally advanced breast tumors. Of women with breast cancer, 126 were prospectively evaluated. All patients underwent (18)F-FDG PET/CT previous to NC. Standard uptake value (SUV) max was calculated in the primary tumor. After NC, residual primary tumor specimen was histopathologically classified according to Miller and Payne tumor regression grades (TRG), from G1 to G5 and in response groups as good responders (G4 or G5), partial responders (G2 or G3), and non-responders (G1). Furthermore, residual lesions were classified following a binary assessment as responders (G4 or G5) and non responders (the rest of cases). The relationship between SUV max with TRG and response groups was evaluated. Of tumors, 127 were assessed (a patient had bilateral breast lesions). TRG were as follows: G1 (27), G2 (27), G3 (32), G4 (11), and G5 (30). Forty-one were classified as good responders, 59 as partial responders, and 27 as non-responders. For the binary assessment, 41 lesions were classified as responders and 86 as non-responders. We found statistical differences (p=0.02) between the mean SUV max and TRG with greater SUV values for G5 compared to the other TRG. Good responders showed greater mean SUV max +/- SD compared to partial responders and non-responders (10.51 +/- 6.64 for good responders, 6.94 +/- 5.81 for partial responders, and 5.23 +/- 2.76 for non responders; p=0.001). Baseline tumor metabolism assessing by FDG PET/CT was associated with the final histopathologic status after neoadjuvant chemotherapy, with greater SUV max values for good responders compared to the less responder cancers. PMID- 25139101 TI - The preoperative lymphocyte to monocyte ratio predicts clinical outcomes in patients with stage II/III gastric cancer. AB - Recently, lymphocyte to monocyte ratio (LMR) has been reported to be associated with clinical outcomes in some types of cancer but has not been explored in gastric cancer. In this study, we analyzed the association between LMR and clinical outcomes in stage II/III gastric cancer patients. Preoperative LMR calculated from peripheral lymphocyte and monocyte with corresponding clinical features from 426 stage II/III gastric cancer patients was noted. Kaplan-Meier method and Cox regression model were applied for overall survival (OS) and recurrence-free survival (RFS). Related with smaller tumor size (p<0.001), increased LMR could predict better OS [hazard ratio (HR), 0.688; 95% confidence interval (CI), 0.521-0.908, p=0.008] and was borderline significantly associated with better RFS (HR, 0.775; 95% CI, 0.592-1.01, p=0.06) in stage II/III gastric cancer patients through multivariable analysis. Subgroup analyses revealed that except stage III patients for RFS which yielded borderline significance (p=0.052), lower LMR was associated with poor clinical outcomes for patients regardless of different stages or whether the patients received adjuvant chemotherapy. The elevated preoperative LMR level was a significant favorable factor in the prognosis of stage II/III gastric cancer patients, especially for those with stage II. However, further validation of our findings is warranted. PMID- 25139102 TI - The lncRNA-MYC regulatory network in cancer. AB - Long non-coding RNAs (lncRNAs) have been widely studied in recent years, and accumulating evidence identified lncRNAs as crucial regulators of various biological processes, including cell cycle progression, chromatin remodeling, gene transcription, and posttranscriptional processing. In addition, the fact that lncRNAs interact with the MYC gene family in human carcinomas has been discovered. This review summarizes the latest progress on the investigation of lncRNAs and MYC, particularly focusing on the interplay between lncRNAs and MYC in cancer to reveal the significance of lncRNA-MYC network in regulating initiation, development, and metastasis of tumors. Further research and collection of clinical data would provide a better understanding of lncRNA-MYC network in cancer diagnosis and treatment. PMID- 25139103 TI - EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective study. AB - Extracellular metalloproteinase inducer (EMMPRIN) and a disintegrin and metalloproteinase (ADAM12) play a major role in cancer invasion and metastasis owing to the fact that they are directly related to the cell microenvironment and extracellular matrix (ECM) degradation. The aim of this study was to search for an answer to the question "whether the determination of EMMPRIN and ADAM12 values especially in urine may be helpful for the early diagnosis of prostate cancer without employing invasive methods" and also to check whether they may be useful for the determination of the patients with high metastasis risk. Peripheral blood and urine from 66 prostate cancer patients (40 local, 20 locally advanced, 6 metastatic) and 14 healthy controls were evaluated by enzyme-linked immunosorbent assay (ELISA) method. Serum EMMPRIN and ADAM12 values of the patients were seen to be statistically higher than the serum EMMPRIN and ADAM12 values of the healthy controls (p=0.01 and p=0.001, respectively). The urine ADAM12 levels were significantly higher in patients (p=0.013). No significant relationships were found between urine EMMPRIN values of the patients and the healthy controls (p>0.05). Positive correlation between urine EMMPRIN-urine ADAM12 tests was found in total patients group (r=0.683, p=0.001). Our preliminary results revealed that serum EMMPRIN and ADAM12 values and urine ADAM12 values may be useful markers in prostate cancer therapy. Due to the high correlation between these two tests, we are of the opinion that the use of urine ADAM12 in clinic may be sufficient and favorable together with prostate-specific antigen (PSA) for treatment. PMID- 25139104 TI - TriMatch comparison of the efficacy of FloSeal versus TachoSil versus no hemostatic agents for partial nephrectomy: results from a large multicenter dataset. AB - OBJECTIVES: To evaluate the efficacy of hemostatic agents, TachoSil and FloSeal, during partial nephrectomy using a large multicenter dataset. METHODS: Data of 1055 patients who underwent partial nephrectomy between January 2009 and December 2012 in 19 Italian centers were collected within an observational multicentric study (RECORd Project). The decision whether or not to use hemostatic agents after renorrhaphy and the type of hemostatic agents applied was adopted according to the centers' and surgeons' preference. A TriMatch propensity score analysis was applied to balance three study groups (no hemostatic agents, TachoSil, FloSeal) for sex, age, surgical indication (elective/relative vs imperative), clinical stage (cT1a vs cT1b), tumor exophyticity, approach (open vs minimally invasive), technique (standard partial nephrectomy vs simple enucleation), preoperative hemoglobin and creatinine. Postoperative complications and variation of hemoglobin and creatinine values between preoperative versus third postoperative day were compared. RESULTS: TriMatch analysis allowed us to obtain 66 well-balanced triplets. No differences were found in terms of outcomes between the study groups. CONCLUSIONS: The present findings suggest that adding hemostatic agents to renorraphy during partial nephrectomy does not provide better surgical outcomes. PMID- 25139105 TI - HES1 as an independent prognostic marker in esophageal squamous cell carcinoma. AB - BACKGROUND: Notch signaling is one of the main involved pathways in cell differentiation and organogenesis, and its deregulation may lead to tumorigenesis. In this pathway, targeted to the CSL (CBF1, Suppressor of Hairless or Lag-1) complex, notch intracellular domain (NICD) releases corepressors and recruits MAML1 as coactivator triggering the activation of notch signaling transcription complex. Hairy enhance of split-1 (HES1) is one of the notch signaling target genes which is a basic helix-loop-helix (bHLH) transcription factor acting as a proliferation stimulator through the suppression of cell cycle inhibitors such as p27 and p21. AIMS: In this study, we aimed to analyze the role of HES1 in the progression of esophageal squamous cell carcinoma (ESCC). METHODS: Messenger RNA (mRNA) expression of HES1 in fresh tumoral tissues and their margin normal samples were assessed in 50 ESCC patients by real-time polymerase chain reaction (RT-PCR). RESULTS: Thirteen out of 50 cases (26 %) had HES1 underexpression, while HES1 overexpression was observed only in 4 (8 %) samples. HES1 underexpression was significantly correlated with tumor depth of invasion (P = 0.035). CONCLUSION: Although we have not observed any significant correlation between the HES1 expression and notch activation in ESCC, this study is the first report that elucidated the HES1 underexpression in ESCC and revealed its correlation with the invasiveness of ESCC. PMID- 25139106 TI - Does multifunctionality matter to US farmers? Farmer motivations and conceptions of multifunctionality in dairy systems. AB - The concept of multifunctionality describes and promotes the multiple non production benefits that emerge from agricultural systems. The notion of multifunctional agriculture was conceived in a European context and largely has been used in European policy arenas to promote and protect the non-production goods emerging from European agriculture. Thus scholars and policy-makers disagree about the relevance of multifunctionality for United States agricultural policy and US farmers. In this study, we explore lived expressions of multifunctional agriculture at the farm-level to examine the salience of the multifunctionality concept in the US. In particular, we investigate rotational grazing and confinement dairy farms in the eastern United States as case studies of multifunctional and productivist agriculture. We also analyze farmer motivations for transitioning from confinement dairy to rotational grazing systems. Through interviews with a range of dairy producers in Wisconsin, Pennsylvania, and New York, we found that farmers were motivated by multiple factors--including improved cow health and profitability--to transition to rotational grazing systems to achieve greater farm-level multifunctionality. Additionally, rotational grazing farmers attributed a broader range of production and non-production benefits to their farm practice than confinement dairy farmers. Further, rotational grazing dairy farmers described a system-level notion of multifunctionality based on the interdependence of multiple benefits across scales--from the farm to the national level--emerging from grazing operations. We find that the concept of multifunctionality could be expanded in the US to address the interdependence of benefits emerging from farming practices, as well as private benefits to farmers. We contend that understanding agricultural benefits as experienced by the farmer is an important contribution to enriching the multifunctionality concept in the US context, informing agri environmental policy and programs, and ultimately expanding multifunctional agricultural practice in the US. PMID- 25139107 TI - Montreal Cognitive Assessment (MoCA)-Italian version: regression based norms and equivalent scores. AB - The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening instrument developed by Nasreddine et al. to detect mild cognitive impairment, a high-risk condition for Alzheimer's disease and other forms of dementia. In this study we report normative data on the MoCA-Italian version, collected on a sample of 225 Italian healthy subjects ranged in age between 60 and 80 years, and in formal education from 5 to 23 years. The global normal cognition was established in accordance with the Mini-Mental State Examination score and with the Prose Memory Test score (Spinnler and Tognoni, Ital J Neurol Sci 6:25-27, 1987). None of the participants had a history of psychiatric, neurological, cerebrovascular disorders or brain injury or took drugs affecting cognition. Linear regression analysis was performed to evaluate the potential effect of age, education and sex on the MoCA total performance score. We provide correction grids to adjust raw scores and equivalent scores with cut-off value to allow comparison between MoCA performance and others neuropsychological test scores that can be administered on the same subject. PMID- 25139108 TI - Are atraumatic spinal needles as efficient as traumatic needles for lumbar puncture? AB - The most frequent complication of lumbar puncture is post lumbar puncture headache (PLPH). Recent studies confirmed that the use of atraumatic spinal needles significantly reduces the risk of PLPH. However, the majority of neurologists still use traumatic needles, possibly caused by misconceptions and beliefs about practical performance of atraumatic spinal needles. Therefore, we investigated the practical characteristics of atraumatic and traumatic spinal needles. An experimental setup with a fluid column was used with (1) a physiological NaCl 0.9 % solution and (2) a high protein content solution. Flow rates and duration of pressure measurements were measured using a traumatic needle and an atraumatic needle. The average flow rate differed less than 10 % between the two needle types with NaCl solution, and for the high protein solution the difference was even smaller. Time taken to perform accurate pressure measurements did not differ between the two needle types using NaCl 0.9 %, and was even slightly shorter for the atraumatic needle when using the high protein solution. Average flow rates and duration of pressure measurements are comparable between atraumatic spinal needles and traumatic needles. Therefore, these performance characteristics are no reason to favor traumatic needles over atraumatic needles. PMID- 25139109 TI - TLR4 enhances histamine-mediated pruritus by potentiating TRPV1 activity. AB - BACKGROUND: Recent studies have indicated that Toll-like receptor 4 (TLR4), a pathogen-recognition receptor that triggers inflammatory signals in innate immune cells, is also expressed on sensory neurons, implicating its putative role in sensory signal transmission. However, the possible function of sensory neuron TLR4 has not yet been formally addressed. In this regard, we investigated the role of TLR4 in itch signal transmission. RESULTS: TLR4 was expressed on a subpopulation of dorsal root ganglia (DRG) sensory neurons that express TRPV1. In TLR4-knockout mice, histamine-induced itch responses were compromised while TLR4 activation by LPS did not directly elicit an itch response. Histamine-induced intracellular calcium signals and inward currents were comparably reduced in TLR4 deficient sensory neurons. Reduced histamine sensitivity in the TLR4-deficient neurons was accompanied by a decrease in TRPV1 activity. Heterologous expression experiments in HEK293T cells indicated that TLR4 expression enhanced capsaicin induced intracellular calcium signals and inward currents. CONCLUSIONS: Our data show that TLR4 on sensory neurons enhances histamine-induced itch signal transduction by potentiating TRPV1 activity. The results suggest that TLR4 could be a novel target for the treatment of enhanced itch sensation. PMID- 25139111 TI - Need of standardization in bariatric surgery: is it time to think about? Comment on Contreras J E, Santander C, Court I, Bravo J. Correlation between age and weight loss after bariatric surgery. Obesity Surgery 2013; 23(8):1286-9. PMID- 25139110 TI - Comparison between rapid and mixed maxillary expansion through an assessment of dento-skeletal effects on posteroanterior cephalometry. AB - BACKGROUND: The aim of this study is to compare the dento-skeletal effects of rapid maxillary expansion (RME) and mixed maxillary expansion (MME), assessed on posteroanterior (PA) cephalograms. METHODS: Treatment groups consisted of 42 patients; mean age in RME group (n = 21,13 female and 8 male subjects) was 8.8 years +/- 1.37 at T0 and 9.6 years +/- 1.45 at T1 and mean age in MME group (n = 21, 12 female and 9 male patients) was 8.9 years +/- 2.34 at T0 and 10.5 years +/ 2.08 at T1. Seventeen bilateral anatomic landmarks, 16 linear (12 skeletal and 4 dental) and 4 angular measurements were assessed for each patient at T0 and T1. Data from the two groups were compared using independent sample t test (p < 0.05). RESULTS: At T0, the groups were similar for all examined variables (p > 0.05). Significant and equal increase of lateronasal and maxillary and upper and lower molar widths (p < 0. 01) occurred in both groups at T1. Significant but different increases were observed for maxillary incisal, upper left first molar lateroorbitale, and maxillary first molar angles (p < 0.001 vs. p < 0.05). Significant increases were reported for upper inter-incisal width apex (p < 0.001) and upper right first molar-lateroorbitale angle (p < 0.05) only in the RME group. At T1, differences in maxillary incisal angle (p < 0.05), upper left first molar-lateroorbitale, and maxillary first molar angles (p < 0.001) were noted. CONCLUSIONS: RME and MME were both effective to increase skeletal transverse dimensions by opening mid-palatal suture in growing patients, while MME was associated with minor dental side effects than RME. PMID- 25139112 TI - Deficits in anticipatory but not consummatory pleasure in people with recent onset schizophrenia spectrum disorders. AB - The majority of studies examining self-reported anticipatory and consummatory pleasure in schizophrenia, as measured on the Temporal Experience of Pleasure Scale (TEPS), have been conducted on chronically ill people with the disorder. In this study, people with a recent-onset schizophrenia spectrum diagnosis (first psychotic episode within one year of study participation) (n=88) and people without a schizophrenia spectrum diagnosis (n=66) were administered the TEPS. People with a schizophrenia spectrum diagnosis reported significantly lower scores of anticipatory, but not consummatory, pleasure on the TEPS compared to the control group. TEPS anticipatory pleasure scores were also significantly, negatively correlated with negative symptoms, but neither TEPS anticipatory nor consummatory pleasure scores were significantly correlated with functioning measures. Our results replicate previous findings with chronically ill people with schizophrenia on the TEPS. PMID- 25139113 TI - Effects of COMT genotype on cognitive ability and functional capacity in individuals with schizophrenia. AB - Cognitive and functional impairments are core features of schizophrenia. This study examined the catechol-O-methyltransferase (COMT) genotype and its relationship to cognition and functional capacity in 188 individuals with schizophrenia or schizoaffective disorder. We found that in a dose-response fashion, individuals with more Met alleles performed significantly better on tests of learning/memory and abstraction. The effects of COMT genotype on cognition were modest, explaining about 3% of the variance in learning/memory and abstraction. Larger studies will be needed to examine the relationships between COMT and other genes and cognitive performance and everyday functioning. PMID- 25139115 TI - Towards a solution of the wires' slippage problem of the Ilizarov external fixator. AB - Clinical experience has indicated that many complications during treatment with the Ilizarov method, and mainly tract infection, are related to decreased wire tension. The aim of this work was to evaluate biomechanically a novel wire tensioning and clamping system that will minimise or even diminish the reduction of the wire pretension during treatment. The proposed approach is based on threading of the wire end in a sufficient length. The wire pretension is applied by twisting a nut on the threaded part of the wires against the ring and is recorded by an incorporated force sensor. For biomechanical evaluation, the frame, consisting of a polyethylene bar, simulating the bone fragment, suspended on two rings, was subjected to a dynamic load of 0-800 N at a frequency of 0.5 Hz. After dynamic loading for 20 min, loss of the initial wire pretension for the novel clamping system ranged between 12 and 16%. The average loss for conventionally clamped wires was 75%. The advantages of the novel clamping system were the much greater ability to sustain the transverse load and the easy and effectual wire re-tensioning. Although wire slippage has been avoided with the novel system, wire material yield is still responsible for a pretension loss. PMID- 25139114 TI - Comparative analysis of pedicular vascular control techniques during laparoscopic nephrectomy: en bloc stapling or separate ligation? AB - OBJECTIVE: To compare the safety and efficacy of en bloc stapling and separate ligation techniques for renal vascular control during laparoscopic nephrectomy. PATIENTS AND METHODS: Clinical data were collected from 60 patients who underwent laparoscopic nephrectomies using en bloc stapling (n = 27, group 1) or the separate ligation method (n = 33, group 2). Comparative analysis was carried out between the two groups, examining operative times, blood loss, intra- and postoperative complications and hospital stay. RESULTS: Compared with the separate ligation method, the en bloc hilar control technique was associated with a shorter total operating time (98 vs. 121 min, p = 0.029). However, both groups were similar in terms of estimated blood loss, hemoglobin drop, changes in creatinine level and postoperative hospital stay. The total complication rates in group 1 and 2 were 3.7 and 15.1%, respectively, with a statistically significant difference. There were no complications related to the use of the endo-GIA stapler and no patients required conversion to open surgery in group 1. In group 2, 2 patients required conversion to open surgery, including 1 due to renal vein bleeding secondary to inaccurate vascular control and the other due to bleeding from the vena cava during dissection. In addition, 1 patient had a superficial bowel injury that was repaired laparoscopically and another had a superficial liver tear that was managed without conversion or transfusion. CONCLUSION: En bloc ligation of the renal hilum is an easy and reliable technique that allows safe and fast control of the renal pedicle. PMID- 25139116 TI - Impact of baseline microbiological status on clinical outcomes in generalized aggressive periodontitis patients treated with or without adjunctive amoxicillin and metronidazole: an exploratory analysis from a randomized controlled clinical trial. AB - AIM: To explore whether subjects harbouring A. actinomycetemcomitans, P. gingivalis or T. forsythia at baseline showed increased clinical benefits with the adjunctive use of systemic amoxicillin and metronidazole (AMX-MET) during non surgical treatment of generalized aggressive periodontitis (GAgP). MATERIAL AND METHODS: Forty one subjects were included in this 6-month randomized placebo controlled clinical trial using a 7-day course of systemic AMX-MET or placebo as adjuncts to non-surgical periodontal therapy. Clinical and microbiological parameters were collected at baseline, 2 and 6 months after treatment. Microbiological cultures were processed for pooled subgingival samples and identities of isolates were determined by PCR for A. actinomycetemcomitans, P. gingivalis and T. forsythia RESULTS: At 6 months, the test treatment resulted in significant additional improvements in the primary outcome variable compared to placebo, and the effect of the adjunctive antimicrobials was not modified by the baseline microbiological status in the primary analysis. However, secondary exploratory subgroup analyses showed improved clinical outcomes in subjects harbouring A. actinomycetemcomitans at baseline compared to subjects who did not harbour this pathogen. CONCLUSIONS: All subjects benefited from the tested adjunctive antimicrobial regimen, although subjects who harboured A. actinomycetemcomitans at baseline may show greater clinical benefits. Larger appropriately powered studies are needed to confirm whether adjunctive AMX-MET is more beneficial for GAgP patients who harbour A. actinomycetemcomitans, along with other key periodontal pathogens. PMID- 25139117 TI - The nonaspanins TM9SF2 and TM9SF4 regulate the plasma membrane localization and signalling activity of the peptidoglycan recognition protein PGRP-LC in Drosophila. AB - Transmembrane 9 (TM9) proteins, or nonaspanins, are a family of proteins conserved throughout evolution and characterized by 9 transmembrane domains. In Drosophila, TM9 superfamily protein member 4 (TM9SF4) and its closest paralogue, TM9SF2, contribute to phagocytosis of various types of particles, while TM9SF4 displays non-redundant requirement in Gram-negative bacteria engulfment. In addition, the two TM9 proteins control the actin cytoskeleton in larval haemocytes and in Drosophila S2 cells. Here, we show that TM9SF4 and TM9SF2 co immunoprecipitate with the peptidoglycan recognition protein (PGRP)-LC, which triggers the Drosophila immune response to bacterial infection. Furthermore, both TM9 proteins co-localize with this receptor in intracellular vesicles and at the plasma membrane in Drosophila S2 cells in culture and in the fly fat body. Silencing TM9SF4 prevents plasma membrane localization of PGRP-LC, whereas silencing TM9SF2 does not, which may account for the non-redundant role of TM9SF4 in phagocytosis of Gram-negative bacteria. Finally, we provide a set of data suggesting that TM9 proteins can prevent inappropriate signalling from the unstimulated receptor. PMID- 25139118 TI - Assessment of coronary artery intimal thickening in patients with a previous diagnosis of Kawasaki disease by using high resolution transthoracic echocardiography: our experience. AB - BACKGROUND: Kawasaki disease (KD) is a generalized systemic vasculitis of unknown etiology involving medium and small size blood vessels, particularly the coronary arteries. In these vessels a progressive stenosis may result from active remodeling with an intimal proliferation and neoangiogenesis. The aim of our study was to assess, by using high-resolution transthoracic 2D Echocardiography, if subjects with a previous diagnosis of Kawasaki disease after several years show a coronary intimal thickening, suggestive of a persistent cardiovascular risk. METHODS: We assessed measurement of thickening, inner diameter and outer diameter of coronary arteries using 2D Echocardiography (Philips E 33 with multy frequency S8-3 and S12-4 probes) and examining the proximal portion of left main coronary artery just above the aortic valve with parasternal short axis view. RESULTS: We found a significant intimal thickening in patients with previous Kawasaki disease compared to healthy controls. In particular, we noticed that also subjects not suffering from coronary impairment in acute phase have higher values of thickening than healthy controls, and this wall thickening may confer a higher cardiovascular risk. CONCLUSIONS: Therefore we concluded that the assessment of coronary artery thickening by high-resolution transthoracic 2D Echocardiography may become an essential instrument to evaluate late cardiovascular risk in subjects with a diagnosis of Kawasaki disease in childhood. PMID- 25139119 TI - Natural compounds in epigenetics: a current view. AB - The successful treatment of many human diseases, including cancer, has come to be considered a major challenge, as patient response to therapy is difficult to predict. Recently, considerable efforts are being focused on the development of new tools to meet the growing demand for personalized medicine. With few exceptions, synthetic compounds have been unable to meet initial expectations for their clinical use. The last twenty years have been characterized by the failure of several drugs in advanced clinical development, possibly due to the insufficient understanding of molecular pathways underlying their mechanism of action. Although the biodiversity of compounds found in nature has been poorly explored until now, the field of naturally occurring drugs is rapidly expanding. Here, we review the current knowledge on the use of natural compounds with particular emphasis on those that display a chromatin remodeling effect coupled with anticancer action. PMID- 25139120 TI - Chronic toxicity and carcinogenicity of semicarbazide hydrochloride in Wistar Hannover GALAS rats. AB - We performed a combined study to determine the chronic toxicity and carcinogenicity of semicarbazide hydrochloride (SEM-HCl). Male and female Wistar Hannover GALAS rats were fed a diet containing SEM-HCl at 0, 10, 50, and 250ppm for 52weeks (10 rats/sex/group) or for 104weeks (50 rats/sex/group). Enlargement of the knee joints was apparent in both sexes at 250ppm. Reduced body weight was observed at 250ppm from week 76 only in males. SEM-HCl exerted no toxic effects on hematology, serum biochemistry, or organ weights. Histopathologically, disarrangement of chondrocytes accompanied by increased connective tissues, and degeneration of articular cartilage were found in males at 50ppm and above and in females at 250ppm. Mild changes in the elastic laminae were observed at 250ppm for both sexes in the chronic toxicity study. There were no significant intergroup differences in the incidences or types of any tumors. Taken together, toxicological effects of chronic exposure to SEM-HCI mainly occurred in the bone, cartilage, and aorta. Based on histopathological findings, the no-observed adverse-effect-level was 10ppm in males and 50ppm in females (equal to 0.6mg/kg/day in males and 3.9mg/kg/day in females). SEM-HCl was not carcinogenic in rats. PMID- 25139121 TI - Toxicological in vitro and subchronic evaluation of LASSBio-596. AB - LASSBio-596, 2-[4-(1,4-tiazinan-4-ylsulfonyl) phenylcarbamoyl] benzoic acid, is an achiral compound containing a subunit carboxylic amide, was capable of preventing induced mechanical and morphological changes in the lungs that commonly caused the onset of asthma. Previous studies to determine the acute toxicity of oral LASSBio-596 at dose of 2000mg/kg caused no deaths in any of the tested animals. To further evaluate the safety of LASSBio-596, in vitro and in vivo tests were carried out. Regarding to in vitro test were used renal, hepatic, pulmonary, cardiac, neurologic and intestinal cell lines. They were evaluated using neutral red (NR) and [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assays. Micronuclei also was performed. Concerning to in vivo was performed subchronic on Wistar rats at doses of 10, 50, and 250mg/kg and zebrafish test. The in vitro tests results showed the safety of LASSBio-596. However, subchronic toxicity study results revealed changes in the blood parameters of amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose and creatine kinase (CK) which is used for cardiotoxicity evaluation, although, did not identify any histopathological alterations. However, zebrafish test demonstrated cardiac damage. It was impossible to estimate the no-observed-adverse-effect-levels and lowest observed-adverse-effect level due to the presence of cardiotoxicity in all tested doses. PMID- 25139122 TI - Investigation of the MICs of fidaxomicin and other antibiotics against Hungarian Clostridium difficile isolates. AB - The aim of this study was to investigate in vitro activities of fidaxomicin and other antibiotics against 188 Clostridium difficile strains collected from different centers of Hungary. C. difficile isolates showed minimum inhibitory concentration (MIC) range for fidaxomicin of <=0.008-0.5 mg/L, with a MIC90 of 0.125 mg/L. Only four isolates (2.1%) had 0.5 mg/L MIC to fidaxomicin. The obtained MICs showed identical distribution to those found in the EUCAST database for wild-type strains. PMID- 25139123 TI - Intra-genomic variation in G + C content and its implications for DNA stable isotope probing. AB - Combining deoxyribonucleic acid (DNA-based) stable isotope probing (DNA-SIP) with high-throughput sequencing provides a powerful culture-independent means to link microbial metabolic function to genomic information and taxonomic identity. DNA buoyant density (BD) in isopycnic gradients is dependent on both isotope incorporation and G + C content. G + C content varies across a genome but is constrained at rrn operons; hence, the ability to resolve isotopically labelled DNA from unlabelled DNA in SIP may vary between small subunit-ribosomal nucleic acid (SSU rRNA) amplicon and shotgun-read sequencing applications. We tested this hypothesis by evaluating the G + C content of genomic DNA fragments that encompassed either an SSU rRNA template ('amplicon-fragments') or a shotgun read template ('shotgun-fragments'). We find that, contrary to expectations, the BD distribution of amplicon-fragments is non-normal and can be highly skewed. Furthermore, the BD distribution of amplicon-fragments can differ substantially from that of shotgun-fragments from the same genome. Our findings demonstrate the impact of G + C content on the downstream applications of DNA-SIP, which will aid in proper experimental design and the development of statistical tests to accurately identify sequences derived from isotopically labelled DNA. PMID- 25139124 TI - The impact of a tumor diagnosis on patients' attitudes toward advance directives. AB - BACKGROUND: Although advance care planning and the completion of advance directives (ADs) are important tools to avoid unwanted aggressive care once patients have lost their decision-making capacity, only a minority of cancer patients are admitted with completed ADs, and little is known about patients' wishes regarding AD consultations. METHODS: For 1 year, every new patient admitted to the hematology/oncology outpatient clinic of the University Hospital Regensburg received a self-administered questionnaire comprising a self evaluation of AD knowledge and questions about preferences regarding consultation partners and the time of consultation. Disease-related data were collected from medical records. Statistics were calculated with SPSS. RESULTS: Of the 500 questionnaires handed out, 394 (75%) were evaluable and analyzed. Twenty-eight percent of the participants had completed an AD (living will or health care proxy). Ninety-two percent of the participants without ADs had never received a consultation offer from any professional involved. Only 20% perceived a clear relation between cancer and AD consultations. More than 50% of the participants without ADs were in favor of consultations 'now' or 'in a few weeks', while more than 40% objected to AD consultations. CONCLUSIONS: Oncology patients have a large unmet demand for AD consultations. However, a relevant percentage of these patients object to AD consultations. Structured and early AD consultation offers should be made, and early discussions about indications for aggressive treatment should take place. PMID- 25139126 TI - Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. AB - INTRODUCTION: Recent reports have significantly halted the enthusiasm regarding androgen-boosting; suggesting that testosterone supplementation (TS) increases cardiovascular (CV) events. AREAS COVERED: In order to overcome some of the limitations of the current evidence, the authors performed an updated systematic review and meta-analysis of all placebo-controlled randomized clinical trials (RCTs) on the effect of TS on CV-related problems. Out of 2747 retrieved articles, 75 were analyzed, including 3016 and 2448 patients in TS and placebo groups, respectively, and a mean duration of 34 weeks. Our analyses, performed on the largest number of studies collected so far, indicate that TS is not related to any increase in CV risk, even when composite or single adverse events were considered. In RCTs performed in subjects with metabolic derangements a protective effect of TS on CV risk was observed. EXPERT OPINION: The present systematic review and meta-analysis does not support a causal role between TS and adverse CV events. Our results are in agreement with a large body of literature from the last 20 years supporting TS of hypogonadal men as a valuable strategy in improving a patient's metabolic profile, reducing body fat and increasing lean muscle mass, which would ultimately reduce the risk of heart disease. PMID- 25139127 TI - Ceftolozane/tazobactam (CXA 201) for the treatment of intra-abdominal infections. AB - During the mid-nineties, 95-97% of intra-abdominal infection (IAI)- associated microbes were susceptible to commonly used antibiotics. Nowadays, in Gram negative bacilli, beta-lactam resistance and the associated co-resistance to other antibiotics leading to multidrug resistance is reaching crisis proportions. This is a critical issue in the treatment of IAIs, especially for complicated IAIs and for those of nosocomial origin in severely ill patients. In this setting, this article reviews the place in the therapeutic armamentarium of ceftolozane/tazobactam, a new cephalosporin/beta-lactamase inhibitor with good activity against extended spectrum beta-lactamase producing Enterobacteriaceae, with stability to AmpC beta-lactamases and good anti-pseudomonal activity being stable against the most common resistance mechanisms driven by mutation in Pseudomonas aeruginosa. A profound review of its in vitro activity, in vivo efficacy in animal models, pharmacodynamics, pharmacokinetics, clinical efficacy in clinical trials in complicated IAIs and safety data is performed. PMID- 25139125 TI - Depression and risk of hospitalization for pneumonia in a cohort study of older Americans. AB - OBJECTIVE: The aim of this study is to determine if depression is independently associated with risk of hospitalization for pneumonia after adjusting for demographics, medical comorbidity, health-risk behaviors, baseline cognition and functional impairments. METHODS: This secondary analysis of prospectively collected data examined a population-based sample of 6704 Health and Retirement Study (HRS) (1998-2008) participants>50years old who consented to have their interviews linked to their Medicare claims and were without a dementia diagnosis. The eight-item Center for Epidemiologic Studies Depression Scale and/or International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) depression diagnoses were used to identify baseline depression. ICD-9 CM diagnoses were used to identify hospitalizations for which the principal discharge diagnosis was for bacterial or viral pneumonia. The odds of hospitalization for pneumonia for participants with depression relative to those without depression were estimated using logistic regression models. Population attributable fractions were calculated to determine the extent that hospitalizations for pneumonia could be attributable to depression. RESULTS: After adjusting for demographic characteristics, clinical factors, and health risk behaviors, depression was independently associated with increased odds of hospitalization for pneumonia (odds ratio [OR]: 1.28, 95% confidence interval [95%CI]: 1.08, 1.53). This association persisted after adjusting for baseline cognition and functional impairments (OR: 1.24, 95%CI: 1.03, 1.50). In this cohort, 6% (95%CI: 2%, 10%) of hospitalizations for pneumonia were potentially attributable to depression. CONCLUSION: Depression is independently associated with increased odds of hospitalization for pneumonia. This study provides additional rationale for integrating mental health care into medical settings in order to improve outcomes for older adults. PMID- 25139128 TI - A cross-sectional exploration of the personality traits of dietitians. AB - BACKGROUND: Personality traits refer to habitual patterns of behaviour, thought and emotions, and have been shown to influence health professionals' career decisions, career development, job satisfaction and retention. There is an opportunity to better understand and support the career pathways of dietitians by exploring their personality traits. The two primary aspects of personality are: (i) temperament traits, which determine automatic emotional responses to experiences, and are generally stable over lifetime, and (ii) character traits, which reflect personal goals and values, and tend to develop with life experience. The present study explored the levels of temperament and character traits of dietitians, as well as their relationship to demographic variables. METHODS: The study comprised a cross-sectional online survey of 346 Australian dietitians [95% female; mean (SD) age 32 (10) years; mean (SD) time since graduation 7 (9) years]. Temperament and character traits were measured by the Temperament and Character Inventory. Key demographic variables were measured to describe career decisions and pathways of dietitians. Multivariate analyses of variance was used to investigate the relationship between demographic variables and personality traits. RESULTS: Levels of several traits were significantly associated with gender, age and highest level of education. In comparison to the general population, the dietitians displayed average levels of Novelty Seeking; high levels of Harm Avoidance, Reward Dependence, Persistence, Self-Directedness and Cooperativeness; and low levels of Self-Transcendence. CONCLUSIONS: The dietitians in the present study displayed levels of personality traits that were similar to other health professionals, although they differed from the general population. These findings are the precursor to further work that may inform recruitment strategies and career counselling in dietetics. PMID- 25139130 TI - Interactions of N2O5 and related nitrogen oxides with ice surfaces: desorption kinetics and collision dynamics. AB - The detailed interactions of nitrogen oxides with ice are of fundamental interest and relevance for chemistry in cold regions of the atmosphere. Here, the interactions of NO, NO2, N2O4, and N2O5 with ice surfaces at temperatures between 93 and 180 K are investigated with molecular beam techniques. Surface collisions are observed to result in efficient transfer of kinetic energy and trapping of molecules on the ice surfaces. NO and NO2 rapidly desorb from pure ice with upper bounds for the surface binding energies of 0.16 +/- 0.02 and 0.26 +/- 0.03 eV, respectively. Above 150 K, N2O4 desorption follows first-order kinetics and is well described by the Arrhenius parameters Ea = 0.39 +/- 0.04 eV and A = 10((15.4+/-1.2)) s(-1), while a stable N2O4 adlayer is formed at lower temperatures. A fraction of incoming N2O5 reacts to form HNO3 on the ice surface. The N2O5 desorption rates are substantially lower on pure water ice (Arrhenius parameters: Ea = 0.36 +/- 0.02 eV; A = 10((15.3+/-0.7)) s(-1)) than on HNO3 covered ice (Ea = 0.24 +/- 0.02 eV; A = 10((11.5+/-0.7)) s(-1)). The N2O5 desorption kinetics also sensitively depend on the sub-monolayer coverage of HNO3, with a minimum in N2O5 desorption rate at a low but finite coverage of HNO3. The studies show that none of the systems with resolvable desorption kinetics undergo ordinary desorption from ice, and instead desorption likely involves two or more surface states, with additional complexity added by coadsorbed molecules. PMID- 25139129 TI - Evaluation of surface roughness and bond strength of quartz fiber posts after various pre-treatments. AB - PURPOSE: Debonding at the post-adhesive interface is a major problem for quartz fiber posts. The objective of this study was to evaluate surface roughness and bond strength of quartz fiber posts after various surface treatments. MATERIALS AND METHODS: Sixty-six quartz fiber posts were randomly divided into six experimental groups (n = 11) including group C, untreated (control); group SB, sandblasted; group SC, silica coated; group HF, hydrofluoric acid-etched; group N, Nd:YAG laser irradiated; group E, Er:YAG laser irradiated. Surface roughness of the posts was measured before and after pre-treatment. They were then bonded to resin cement and tensile bond strength was determined in a universal testing machine. Furthermore, two-way ANOVA and post hoc comparison tests (alpha = 0.05) were performed on all data. RESULTS: The highest mean force value was observed in group SB and followed by group E. Tukey's HSD test showed that there was no statistical difference between group SB and group E (p = 0.673). The highest mean roughness value was observed in group SB and a significant difference was found between group SB and all other groups (p < 0.001). This study reveals that sandblasting and Er:YAG laser irradiation provided a significant increase in bond strength between quartz fiber posts and resin cement. CONCLUSIONS: Sandblasting or Er:YAG laser-irradiation of the surface of the quartz fiber post before cementation is recommended for increasing retention. PMID- 25139131 TI - Magnetic resonance imaging characteristics of equine head disorders: 84 cases (2000-2013). AB - The equine head is an anatomically complex area, therefore advanced tomographic imaging techniques, such as computed tomography or magnetic resonance imaging (MRI), are often required for diagnosis and treatment planning. The purpose of this multicenter retrospective study was to describe MRI characteristics for a large sample of horses with head disorders. Horses imaged over a period of 13 years were recruited. Eighty-four horses met the inclusion criteria, having neurological (n = 65), sinonasal (n = 14), and soft tissue (n = 5) disorders. Magnetic resonance imaging accurately depicted the anatomy and allowed identification of the primary lesion and associated changes. There were good correlations between MRI findings and intraoperative or postmortem results. Magnetic resonance imaging showed the exact localization of the lesions, their size, and relation to surrounding structures. However, in the neurological group, there were 45 horses with no MRI abnormalities, 29 of which had a history of recurrent seizures, related to cryptogenic epilepsy. Magnetic resonance imaging was otherwise a valuable diagnostic tool, and can be used for studying a broad range of head disorders using either low-field or high-field magnets. PMID- 25139132 TI - Primary aerodigestive presentations of Pierre Robin sequence/complex and predictive factors of airway type and management. AB - OBJECTIVE: To document the mode and age of primary aerodigestive presentation of Pierre Robin sequence/complex (PRS/C) children to the otolaryngologist and to explore predictive factors of upper airway type and management. METHODS: This is a retrospective cohort study conducted in a tertiary pediatric referral center. A prospective surgical database was searched for children who were diagnosed with PRS/C. Demographics, presenting complaint, secondary diagnoses, type of upper airway obstruction, secondary airway lesions, presence of cleft palate, and airway interventions were collected. Multiple linear regression analysis was performed to predict upper airway obstruction type and intervention. RESULTS: Seventy-seven potentially eligible patients were identified. Forty-six were included (20 females). Mean age at presentation was 20.4+/-36.9 months (range 1 191.25 months). Twenty-three primarily presented with respiratory failure, 14 with sleep disordered breathing, and nine with swallowing dysfunction. Children with presentations other than respiratory failure were older (p=0.004). Nineteen were syndromic. Overt cleft palate was more common in those presenting with respiratory failure (p=0.01). The type of airway obstruction encountered and use of tracheostomy were positively predicted by the primary presenting feature of respiratory failure (p<0.05) and male gender (p<0.05). CONCLUSION: A substantial number of PRS/C patients present later than the neonatal period with presentations other than respiratory failure. Both male gender and presentation with respiratory failure predicted a more severe airway obstruction type and the need for trachesotomy. PMID- 25139133 TI - Hear here: children with hearing loss learn words by listening. AB - OBJECTIVES: Early use of hearing devices and family participation in auditory verbal therapy has been associated with age-appropriate verbal communication outcomes for children with hearing loss. However, there continues to be great variability in outcomes across different oral intervention programmes and little consensus on how therapists should prioritise goals at each therapy session for positive clinical outcomes. This pilot intervention study aimed to determine whether therapy goals that concentrate on teaching preschool children with hearing loss how to distinguish between words in a structured listening programme is effective, and whether gains in speech perception skills impact on vocabulary and speech development without them having to be worked on directly in therapy. METHOD: A multiple baseline across subjects design was used in this within subject controlled study. 3 children aged between 2:6 and 3:1 with moderate severe to severe-profound hearing loss were recruited for a 6-week intervention programme. Each participant commenced at different stages of the 10-staged listening programme depending on their individual listening skills at recruitment. Speech development and vocabulary assessments were conducted before and after the training programme in addition to speech perception assessments and probes conducted throughout the intervention programme. RESULTS: All participants made gains in speech perception skills as well as vocabulary and speech development. Speech perception skills acquired were noted to be maintained a week after intervention. In addition, all participants were able to generalise speech perception skills learnt to words that had not been used in the intervention programme. CONCLUSIONS: This pilot study found that therapy directed at listening alone is promising and that it may have positive impact on speech and vocabulary development without these goals having to be incorporated into a therapy programme. Although a larger study is necessary for more conclusive findings, the results from this preliminary study are promising in support of emphasise on listening skills within auditory-verbal therapy programmes. PMID- 25139134 TI - Ketamine peritonsillar infiltration during tonsillectomy in pediatric patients: An updated meta-analysis. AB - OBJECTIVES: Peri-operative ketamine peritonsillar infiltration in children can reduce the incidence of postoperative nausea and vomiting (PONV), but its postoperative analgesic time is short. A previous meta-analysis in 2011 was inconclusive due to insufficient data. Consequently, we updated the meta-analysis to verify the role of ketamine peritonsillar infiltration for tonsillectomy in pediatric patients. METHODS: Ten randomized controlled trials with a total of 522 cases were included. Pain intensity was measured by standard modified CHEOPS score. RESULTS: The pain scores of ketamine group at 30 min and 60 min were significantly lower than placebo group after surgery [weighted mean difference (WMD) -1.20, 95% CI -2.20 to -0.19, P=0.02; WMD -1.71, 95% CI -2.12 to -0.22, P=0.02]. Analgesic requirement in ketamine group were less than placebo group [risk ratio (RR) 0.51, 95% CI 0.26-0.97; P=0.04]. Moreover, the incidence of PONV was lower in ketamine group. (RR 0.73, 95% CI 0.54-0.97; P=0.03). However, there were no differences between these two groups in operation time, anesthesia time, first analgesic time and pain score at 120 min. CONCLUSIONS: Compared to placebo, ketamine peritonsillar infiltration can relieve postoperative pain within one hour but not at 120 min and reduces analgesic requirement and incidence of PONV. Moreover, there was no difference in the first analgesic time. PMID- 25139135 TI - Unique migration of a dental needle into the parapharyngeal space: successful removal by an intraoral approach and simulation for tracking visibility in X-ray fluoroscopy. AB - OBJECTIVES: The first objective was to describe a novel case of migration of a broken dental needle into the parapharyngeal space. The second was to address the importance of simulation elucidating visualization of such a thin needle under X ray fluoroscopy. METHODS: Clinical case records (including computed tomography [CT] and surgical approaches) were reviewed, and a simulation experiment using a head phantom was conducted using the same settings applied intraoperatively. RESULTS: A 36-year-old man was referred after failure to locate a broken 31-G dental needle. Computed tomography revealed migration of the needle into the parapharyngeal space. Intraoperative X-ray fluoroscopy failed to identify the needle, so a steel wire was applied as a reference during X-ray to locate the foreign body. The needle was successfully removed using an intraoral approach with tonsillectomy under surgical microscopy. The simulation showed that the dental needle was able to be identified only after applying an appropriate compensating filter, contrasting with the steel wire. CONCLUSION: Meticulous preoperative simulation regarding visual identification of dental needle foreign bodies is mandatory. Intraoperative radiography and an intraoral approach with tonsillectomy under surgical microscopy offer benefits for accessing the parapharyngeal space, specifically for cases medial to the great vessels. PMID- 25139136 TI - Exploring the implementation of a medication adherence programme by community pharmacists: a qualitative study. AB - BACKGROUND: Medication adherence has been identified as an important factor for clinical success. Twenty-four Swiss community pharmacists participated in the implementation of an adherence support programme for patients with hypertension, diabetes mellitus and/or dyslipidemia. The programme combined tailored consultations with patients about medication taking (expected at an average of one intervention per month) and the delivery of each drug in an electronic monitoring system (MEMS6TM). OBJECTIVE: To explore pharmacists' perceptions and experiences with implementation of the medication adherence programme and to clarify why only seven patients were enrolled in total. SETTING: Community pharmacies in French-speaking Switzerland. METHOD: Individual in-depth interviews were audio-recorded, with 20 of the pharmacists who participated in the adherence programme. These were transcribed verbatim, coded and thematically analysed. Process quality was ensured by using an audit trail detailing the development of codes and themes; furthermore, each step in the coding and analysis was verified by a second, experienced qualitative researcher. MAIN OUTCOME MEASURE: Community pharmacists' experiences and perceptions of the determining factors influencing the implementation of the adherence programme. RESULTS: Four major barriers were identified: (1) poor communication with patients resulting in insufficient promotion of the programme; (2) insufficient collaboration with physicians; (3) difficulty in integrating the programme into pharmacy organisation; and (4) insufficient pharmacist motivation. This was related to the remuneration perceived as insufficient and to the absence of clear strategic thinking about the pharmacist position in the health care system. One major facilitator of the programme's implementation was pre-existing collaboration with physicians. CONCLUSION: A wide range of barriers was identified. The implementation of medication adherence programmes in Swiss community pharmacies would benefit from an extended training aimed at developing communication and change management skills. Individualised onsite support addressing relevant barriers would also be necessary throughout the implementation process. PMID- 25139137 TI - Barriers to the implementation of advanced clinical pharmacy services at Portuguese hospitals. AB - BACKGROUND: In some countries, such as Portugal, clinical pharmacy services in the hospital setting may be implemented to a lower extent than desirable. Several studies have analysed the perceived barriers to pharmacy service implementation in community pharmacy. OBJECTIVE: To identify the barriers towards the implementation of advanced clinical pharmacy services at a hospital level in Portugal, using medication follow-up as an example. SETTING: Hospital pharmacies in Portugal. METHODS: A qualitative study based on 20 face-to-face semi structured interviews of strategists and hospital pharmacists. The interview guide was based on two theoretical frameworks, the Borum's theory of organisational change and the Social Network Theory, and then adapted for the Portuguese reality and hospital environments. A constant comparison process with previously analysed interviews, using an inductive approach, was carried out to allow themes to emerge. Themes were organised following the Leavitt's Organizational Model: functions and objectives; hospital pharmacist; structure of pharmacy services; environment; technology; and medication follow-up based on the study topic. MAIN OUTCOME MEASURE: Barriers towards practice change. RESULTS: Medication follow-up appeared not to be a well-known service in Portuguese hospital pharmacies. The major barriers at the pharmacist level were their mind set, resistance to change, and lack of readiness. Lack of time, excessive bureaucratic and administrative workload, reduced workforce, and lack of support from the head of the service and other colleagues were identified as structural barriers. Lack of access to patients' clinical records and cumbersome procedures to implement medication follow-up were recognised as technological barriers. Poor communication with other healthcare professionals, and lack of support from professional associations were the major environmental barriers. CONCLUSION: Few of the barriers identified by Portuguese hospital pharmacists were consistent with previous reports from community pharmacy. The mind-set of pharmacists and predetermined attitudes are recognised as barriers that can give rise to new perceived barriers. PMID- 25139138 TI - Reply: To PMID 23535238. PMID- 25139139 TI - Thyroid screening in pregnancy. AB - The adverse impact of overt hypothyroidism that complicates pregnancy outcomes is well-established and not debated. For more than a decade, however, endocrinologists and obstetricians have been debating whether screening for subclinical thyroid disorders during pregnancy should be routine or should continue to be based on symptoms and risk factors. Several observational studies have suggested that offspring of women with asymptomatic thyroid dysfunction were at increased risk for impaired neurodevelopment. Other studies have suggested that pregnant women with subclinical thyroid disease, particularly those identified with an elevated thyroid-stimulating hormone (TSH) level may be at increased risk for pregnancy complications such as fetal death, preterm birth, or placental abruption. These data have prompted both obstetric and endocrinologic professional societies to draft recommendations regarding screening for thyroid disease during pregnancy, some of which are not entirely based on available evidence. The prevalence of overt thyroid disease is estimated to be 1-2 per 1000 pregnancies and historically has not been considered high enough to justify routine screening. Lower TSH thresholds (>2.5 mU/L) for the diagnosis of hypothyroidism have been promoted, and women with subclinical thyroid dysfunction commonly are included in estimates of thyroid disease during pregnancy, both of which exaggerate prevalence rates. The most compelling recent evidence on this issue has come from the Controlled Antenatal Thyroid Screening trial. After almost 22,000 pregnant women were screened for either isolated high TSH or isolated low free thyroxine level, 390 children of treated women with either diagnosis were compared with 404 children of similar women who were not treated during pregnancy. Treatment had no effect on mean offspring IQ at age 3 years or the number of children with an IQ <85. Authors of this landmark study concluded that antenatal screening and maternal treatment for women with subclinical thyroid dysfunction did not result in improved cognitive function. An ongoing intervention trial conducted by the Eunice Kennedy-Shriver National Institute of Child Health and Human Development's Maternal-Fetal Medicine Units Network will provide further clarity to this important question. In the interim, the debating authors have concluded, after careful review of the currently published literature, that routine screening for subclinical thyroid dysfunction during pregnancy is not currently warranted at this time. PMID- 25139140 TI - Impact of robotic operative efficiency on profitability. PMID- 25139142 TI - In situ observation of model catalysts under reaction conditions using X-ray core level spectroscopy. AB - Chemical reactions at solid surfaces are of great importance in heterogeneous catalysis and the understanding of their reaction mechanisms has been challenged for a long time by a wide variety of approaches. In situ observation of model catalysts under reaction conditions is a promising approach to understand the mechanisms. Toward this aim we have been developing several spectroscopic techniques using synchrotron-radiation X-rays. In this Personal Account, synchrotron-radiation-based X-ray core-level spectroscopies for in situ observation are introduced and some of their applications in studying the mechanisms of catalytic reactions are highlighted. Future directions for further development of these spectroscopies are also described. PMID- 25139141 TI - Life in urban areas and breast cancer risk in the French E3N cohort. AB - It has been suggested that women living in urban areas are at higher risk of breast cancer (BC) compared to women living in rural areas. However, most published studies on this topic are ecological and did not adjust for individual BC risk factors. We investigated this hypothesis in a French prospective cohort. Cox proportional hazards regression models were used to evaluate the association between birth or residence in an urban area and BC risk among 75,889 women of the French E3N cohort (aged 38-66 years at recruitment in 1990) before and after adjustment for known BC risk factors and stratifying on birth cohort. From 1990 to 2008, a total of 5,145 BC cases were diagnosed. Being born in an urban area was associated with BC risk before (HR 1.11, 95% CI 1.05-1.18) and after (HR 1.07, 95% CI 1.01-1.14) adjustment for known BC risk factors. Living in an urban area in 1990 was not associated with BC risk. Being born in an urban area is associated with a weak increase in BC risk. This may be suggestive of higher exposure to air pollution and to other environmental exposures, to be investigated in future studies. PMID- 25139143 TI - Morphometric analysis and lymph node yield in laparoscopic complete mesocolic excision performed by supervised trainees. AB - BACKGROUND: Complete mesocolic excision with central vascular ligation (CME) produces an optimal colonic cancer specimen. The ability of expert laparoscopic surgeons to produce equivalent specimens is unknown. METHODS: Fresh specimen photographs and clinicopathological data from patients undergoing laparoscopically assisted CME at St Mark's Hospital, Harrow, were submitted for independent pathological review. Surgery was performed by a mixture of consultant specialists and trainees under consultant specialist supervision, between February 2010 and July 2011. The planes of surgery were graded and tissue morphometry was performed using standard methods. The results were compared with published data from open CME and non-CME surgery. RESULTS: In total, 69 patients were identified, and in 96 per cent resection was performed completely or partially by surgical trainees. Laparoscopic CME produced a similar specimen to open CME. The laparoscopic mesocolic plane resection rate was similar to that for open surgery (90 versus 88 per cent). The distance between the bowel wall and site of vascular division was similar for laparoscopic and open right-sided CME (92 versus 95 mm respectively). The corresponding values for left-sided CME were also similar (103 versus 107 mm). Compared with values from two non-CME series, laparoscopic CME had a higher mesocolic plane rate (90 versus 40 and 48 per cent), and resected more tissue between the bowel wall and the vascular division (right-sided: 92 versus 72 and 76 mm; left-sided: 103 versus 85 and 70 mm). The lymph node yield remained low following laparoscopic CME compared with open CME (median 18 versus 32; P < 0.001) and identical to that of non-CME surgery (median 18). CONCLUSION: Laparoscopic CME can be performed to the same standard as open surgery by supervised trainees. However, this did not increase the lymph node yield. PMID- 25139144 TI - Shear rate normalization is not essential for removing the dependency of flow mediated dilation on baseline artery diameter: past research revisited. AB - A ratio index (FMD%) is used ubiquitously to scale (by simple division) brachial artery flow-mediated dilation (Ddiff) in direct proportion to baseline diameter (Dbase). It is now known that Ddiff is inversely proportional to Dbase rendering FMD% wholly inappropriate. Consequently, FMD% is still substantially dependent on Dbase. Although this problem is grounded in statistics, normalization of FMD% for the change in arterial shear rate (DeltaSR) has been proposed to remove this Dbase-dependency. It was hypothesized that, if the flow-mediated response is scaled properly to Dbase in the first place, shear rate normalization would not be needed to remove Dbase-dependency. Dedicated software (Digitizelt) was employed to extract the data from a seminal study on FMD% normalization. The underlying allometric relationship between Dbase and peak diameter (Dpeak) was described. The re-analyses revealed that the absolute change in arterial diameter was strongly inversely proportional to Dbase (r= - 0.7, P < 0.0005). The allometric exponent for the Dbase-Dpeak relationship was 0.82 (95% CI: 0.78-0.86) rather than the value of 1 needed for appropriate use of FMD%. The allometric approach completely eliminated the originally reported dependency on Dbase without any need for DeltaSR normalization (r=0.0, P=0.96). The correlation between DeltaSR and FMD% reduced from 0.69 to 0.37, when adjusted for Dbase. In conclusion, this new re-analysis of data from an influential study demonstrates that the FMD%-Dbase correlation is caused by the inappropriate size-scaling properties of FMD% itself. Removal of Dbase-dependency via FMD%/DeltaSR normalization is not essential at all if allometric scaling is applied to isolate the flow-mediated response in the first place. Consequently, the influence of DeltaSR on this properly scaled response can also be isolated and quantified accurately without the confounding influence of Dbase. PMID- 25139145 TI - Contribution of generative leisure activities to cognitive function in elderly Sri Lankan adults. AB - OBJECTIVES: To examine the unique contribution of generative leisure activities, defined as activities motivated by a concern for others and a need to contribute something to the next generation. DESIGN: Cross-sectional survey. SETTING: Peri urban and rural area in southern Sri Lanka. PARTICIPANTS: Community-dwelling adults aged 60 and older (N = 252). MEASUREMENTS: The main predictors were leisure activities, grouped into generative, social, or solitary. The main outcome was cognitive function, assessed using the Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: More-frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the effect of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured using the MoCA (beta = 0.47, 95% confidence interval (CI) = 0.11-0.83) and the IQCODE (beta = -0.81, 95% CI = -1.54 to 0.09). In this combined model, solitary activities were also independently associated with slower cognitive decline using the MoCA (beta = 0.40, 95% CI = 0.16-0.64) but not the IQCODE (beta = -0.38, 95% CI = -0.88-0.12); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully according to sex. CONCLUSION: Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline in elderly adults. PMID- 25139146 TI - The patterns of health care utilization by elderly Europeans: frailty and its implications for health systems. AB - OBJECTIVE: To examine the patterns of health care utilization by the elderly and test the influence of functional decline. DATA SOURCE AND STUDY DESIGN: We used the three regular waves of the SHARE survey to estimate the influence of frailty on health care utilization in 10 European countries. We controlled for the main correlates of frailty and unobserved individual effects. RESULTS: The frail elderly increase their primary and hospital care utilization before the onset of disability. Multimorbidity moderates the effect of frailty on care utilization. CONCLUSIONS: The prevalence of frailty is high in most countries and is expected to increase. This renders frailty prevention and remediation efforts imperative for two complementary reasons: to promote healthier aging and to reduce the burden on health systems. PMID- 25139147 TI - Antimicrobial light-activated materials: towards application for food and environmental safety. AB - AIMS: To produce light-activated antimicrobial materials composed of the photodynamic dye phloxine B incorporated into paper or cellulose membranes and to investigate ability of these materials to decrease bacterial loads on their surfaces as well as on food surfaces that were in contact with these materials under illumination with regular white light. METHODS AND RESULTS: Antimicrobial cellulose-based materials with incorporated phloxine B were produced using a layer-by-layer deposition method. Antimicrobial properties of the materials were tested in model systems as well as for decontamination of food and food contact surfaces. Pseudomonas aeruginosa, Listeria monocytogenes and Bacillus anthracis were efficiently killed by exposure of the bacterial suspension to the dye containing material under illumination with white light, but Salmonella Typhimurium and Escherichia coli O157:H7 were only partially affected. Application of the materials for decontamination of food surfaces artificially contaminated with L. monocytogenes was shown to be ineffective, while the self decontamination of the material surface by exposure to white light resulted in eradication of L. monocytogenes cells from the material surface. CONCLUSIONS: The developed materials showed significant self-decontaminating ability when under illumination; however, decontamination of food surfaces in contact with the developed materials was not achieved. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrates the antibacterial activity of materials with incorporated photodynamic dyes when under illumination with regular-intensity white light. Possible uses of the light-activated antimicrobial materials for food processing, as food contact surfaces, and surfaces in public areas to prevent cross contamination are discussed. PMID- 25139148 TI - Brain tumor cells in circulation are enriched for mesenchymal gene expression. AB - Glioblastoma (GBM) is a highly aggressive brain cancer characterized by local invasion and angiogenic recruitment, yet metastatic dissemination is extremely rare. Here, we adapted a microfluidic device to deplete hematopoietic cells from blood specimens of patients with GBM, uncovering evidence of circulating brain tumor cells (CTC). Staining and scoring criteria for GBM CTCs were first established using orthotopic patient-derived xenografts (PDX), and then applied clinically: CTCs were identified in at least one blood specimen from 13 of 33 patients (39%; 26 of 87 samples). Single GBM CTCs isolated from both patients and mouse PDX models demonstrated enrichment for mesenchymal over neural differentiation markers compared with primary GBMs. Within primary GBMs, RNA in situ hybridization identified a subpopulation of highly migratory mesenchymal tumor cells, and in a rare patient with disseminated GBM, systemic lesions were exclusively mesenchymal. Thus, a mesenchymal subset of GBM cells invades the vasculature and may proliferate outside the brain. SIGNIFICANCE: GBMs are locally invasive within the brain but rarely metastasize to distant organs, exemplifying the debate over "seed" versus "soil." We demonstrate that GBMs shed CTCs with invasive mesenchymal characteristics into the circulation. Rare metastatic GBM lesions are primarily mesenchymal and show additional mutations absent in the primary tumor. PMID- 25139149 TI - Haematological and biochemical reference intervals for free-ranging brown bears (Ursus arctos) in Sweden. AB - BACKGROUND: Establishment of haematological and biochemical reference intervals is important to assess health of animals on individual and population level. Reference intervals for 13 haematological and 34 biochemical variables were established based on 88 apparently healthy free-ranging brown bears (39 males and 49 females) in Sweden. The animals were chemically immobilised by darting from a helicopter with a combination of medetomidine, tiletamine and zolazepam in April and May 2006-2012 in the county of Dalarna, Sweden. Venous blood samples were collected during anaesthesia for radio collaring and marking for ecological studies. For each of the variables, the reference interval was described based on the 95% confidence interval, and differences due to host characteristics sex and age were included if detected. To our knowledge, this is the first report of reference intervals for free-ranging brown bears in Sweden. RESULTS: The following variables were not affected by host characteristics: red blood cell, white blood cell, monocyte and platelet count, alanine transaminase, amylase, bilirubin, free fatty acids, glucose, calcium, chloride, potassium, and cortisol. Age differences were seen for the majority of the haematological variables, whereas sex influenced only mean corpuscular haemoglobin concentration, aspartate aminotransferase, lipase, lactate dehydrogenase, beta-globulin, bile acids, triglycerides and sodium. CONCLUSIONS: The biochemical and haematological reference intervals provided and the differences due to host factors age and gender can be useful for evaluation of health status in free-ranging European brown bears. PMID- 25139153 TI - Dynamic changes in composition of extracts of natural products as monitored by in situ NMR. AB - The direct in situ NMR observation and quantification, based on the aldehyde -CH chemical shift region, of the inter-conversion of secoiridoid derivatives due to temperature and solvent effects is demonstrated in complex extracts of natural products without prior isolation of the individual components. The equilibrium between the aldehyde hydrate form and the dialdehyde form of the oleuropein aglycon of an olive leaf aqueous extract in D(2)O was shown to be temperature dependent. The resulting thermodynamic values of the Van't Hoff plot with DeltaH(o) = -26.34 +/- 1.00 kJ mol(-1) and TDeltaS degrees (298 K) = -24.70 +/- 1.00 kJ mol(-1) demonstrate a significant entropy term which nearly compensates the effect of enthalpy at room temperature. The equilibrium between the two diastereomeric hemiacetal forms and the dialdehyde form of the oleuropein 6-O beta-d-glucopyranoside aglycon of an olive leaf aqueous extract in CD(3) OD was also shown to be strongly temperature dependent again because of the significant entropy term (TDeltaS degrees (298 K) = -26.50 +/- 1.39 kJ mol(-1)) compared with that of the enthalpy term (DeltaH(o) = -36.64 +/- 1.46 kJ mol(-1)). This is the first demonstration of the significant role of the entropy parameter in determining the equilibrium of chemical transformations in complex mixtures of natural products due to solvent and temperature effects. PMID- 25139151 TI - Evaluation of Hounsfield Units as a predictive factor for the outcome of extracorporeal shock wave lithotripsy and stone composition. AB - The objective of this study was to evaluate the utility of the Hounsfield Unit (HU) values as a predictive factor of extracorporeal shock wave lithotripsy outcome for ureteral and renal stones. We also assessed the possibility that HU values could be used to predict stone composition. A retrospective study was performed to measure stone HU values in 260 patients who underwent extracorporeal shock wave lithotripsy (ESWL) for solitary renal and ureteral stones from July 2007 to January 2012. Stone volume, location, skin-to-stone distance, stone HU values, and stone composition were assessed. Success of ESWL was defined as: (1) being stone-free or (2) residual stone fragments <4 mm after 3 months by radiography. Of the 260 assessed patients, 141 (54.2%) were stone-free, 32 (12.3%) had residual stone fragments <4 mm (clinically insignificant stone fragments), and 87 (33.5%) had residual stone fragments >=4 mm after one round of ESWL. Multivariate analysis revealed that stone location and mean HU were significant predictors of ESWL success. Receiver operating characteristic curves defined cutoff values for predicting treatment outcome. Treatment success rates were significantly higher for stones <815 HU than with stones >815 HU (P < 0.0265). HU of calcium oxalate and calcium phosphate stones were higher than those of uric acid stones, but we could not differentiate between calcium oxalate monohydrate and calcium oxalate dihydrate stones. Evaluation of stone HU values prior to ESWL can predict treatment outcome and aid in the development of treatment strategies. PMID- 25139150 TI - Comparative evaluation of efficacy of use of naftopidil and/or celecoxib for medical treatment of distal ureteral stones. AB - We performed a randomized, prospective study to assess the possible role of combined a1D-receptor antagonist naftopidil and nonsteroidal anti-inflammatory hormones celecoxib for the spontaneous expulsion of distal ureteral stones. Patients were randomized to one of the three treatment groups. Treatment group 1 patients received naftopidil 50 mg/day, group 2 patients received naftopidil 50 mg/day plus celecoxib 200 mg (Take two capsules (400 mg) by mouth immediately, then take one capsule (200 mg) by mouth every 12 h), and group 3 patients received celecoxib 200 mg (Take two capsules (400 mg) by mouth immediately, then take one capsule (200 mg) by mouth every 12 h). All patients were instructed to drink at least 2 L of fluids daily. Pain descriptions were recorded by the patients using the visual analog scale. All patients were followed up for 2 weeks. A total of 105 patients provided consent and 103 patients completed the study. Stone expulsion was observed in 29 patients in group 1 (29 of 35, 82.86 %), 33 patients in group 2 (33 of 35, 94.29 %) and 20 patients in group 3 (20 of 33, 60.61 %). A statistically significant difference was noted with Chi-square testing for stone expulsion rate between groups 1 and 3, and groups 2 and 3 (P = 0.04 and P = 0.000, respectively). Kaplan-Meier curves were plotted to access the expulsion rate of each group over time. A significant difference was shown for the expulsion rate between the group 3 and the other two groups. (P < 0.001 by log-rank test).Average time to expulsion for groups 1, 2 and 3 was 8.00 +/- 2.07, 7.70 +/- 2.34 and 10.65 +/- 2.92 days, respectively (P = 0.000). Treatment with naftopidil and celecoxib appears to be beneficial in distal ureter stone clearance, shortened the expulsion time, and could be used reliably and successfully to reduce the frequency and intensity of the pain episodes particularly. PMID- 25139154 TI - High-performance photoelectrochemical cells based on a binuclear ruthenium catalyst for visible-light-driven water oxidation. AB - Two photoanodes based on a binuclear (2) and a mononuclear ruthenium (3) water oxidation catalysts were assembled in combination with a molecular photosensitizer (1) by using a co-adsorption method. The anodes were used in dye sensitized photoelectrochemical cells (DS-PECs) for visible-light-driven water splitting. A DS-PEC device using TiO2 (1+2) as working electrode (WE) exhibits better performance than TiO2 (1+3) as WE in light-driven water splitting. Detailed photoelectrochemical studies on these DS-PEC devices are discussed. PMID- 25139156 TI - A call to wellness - Whitiwhitia i te ora: exploring Maori and occupational therapy perspectives on health. AB - The World Health Organization records that indigenous peoples throughout the world experience poor health. The concept of health was explored from a Maori world view and compared with occupational therapy perspectives. The aim was to understand and value indigenous knowledge and promote culturally safe responsive practice. Maori methodologies were employed to protect the Maori knowledge shared in the study. This involved applying seven principles, including respect for people, be cautious, and look, listen, and speak. Perspectives on health and wellbeing were collected in 2008-2009 from indigenous occupational therapists, other occupational therapists and indigenous health practitioners using interviews and a questionnaire. The findings are presented as a conceptual framework, depicting a whare, a Maori meeting house to show relationships between culture and health. Key concepts held by occupational therapists and Maori were spirituality, holistic views, client responsive practice, and environmental contexts. Areas of difference were the focus on occupations, the interdependence of indigenous relationships, and the place of the extended family in supporting wellness. A strength was the respect for Maori methodologies and limitations were the number of participants (N = 23) and the small proportion of Maori therapists in Aotearoa/New Zealand. RECOMMENDATIONS: Attention to culture is vital for appropriate, safe, and responsive practice. The conceptual framework provides a tool to inform, guide, and evaluate practice understandings. It acknowledges the importance of the individual within their extended family, their natural environment, and the historical, social, and political realities of living as Maori. Further research should explore the use of the framework and interaction between occupational therapy practice and specific indigenous cultures. PMID- 25139157 TI - A simple thoracoscopic plication technique for diaphragmatic eventration in neonates and infants: technical details and initial results. AB - PURPOSE: Existing minimal-access surgical approaches for correction of symptomatic diaphragmatic eventration may be technically difficult in neonates and infants. We report technical details and initial outcomes of a novel, simple thoracoscopic repair technique. METHODS: The technique uses one 3-mm camera port, a 3-mm instrument incision without a port, and an 18-gauge spinal needle, which is passed through the chest wall into the pleural space. The excess diaphragm is first plicated over the needle, after which a non-absorbable suture is passed through the needle and tied extracorporeally. The needle is passed repeatedly until the desired degree of tension is achieved. A retrospective review was performed for all patients undergoing repair by this technique. RESULTS: Nine patients have undergone thoracoscopic plication at a median age of 3 months (range 0.2-13.2 mos.) and a median weight of 4.5 kg (range 2.3-8.2 kg). No organ injuries or conversions to thoracotomy occurred. Median operative time was 60 min. Patients repaired beyond the neonatal period were extubated in the operating room. There were two post-operative pneumothoraces. No recurrences have been seen at a mean follow-up of 17 months. CONCLUSION: This technique of thoracoscopic diaphragm plication is safe, effective, and technically straightforward in neonates and infants. PMID- 25139155 TI - Muscle ectopic fat deposition contributes to anabolic resistance in obese sarcopenic old rats through eIF2alpha activation. AB - Obesity and aging are characterized by decreased insulin sensitivity (IS) and muscle protein synthesis. Intramuscular ceramide accumulation has been implicated in insulin resistance during obesity. We aimed to measure IS, muscle ceramide level, protein synthesis, and activation of intracellular signaling pathways involved in translation initiation in male Wistar young (YR, 6-month) and old (OR, 25-month) rats receiving a low- (LFD) or a high-fat diet (HFD) for 10 weeks. A corresponding cellular approach using C2C12 myotubes treated with palmitate to induce intracellular ceramide deposition was taken. A decreased ability of adipose tissue to store lipids together with a reduced adipocyte diameter and a development of fibrosis were observed in OR after the HFD. Consequently, OR fed the HFD were insulin resistant, showed a strong increase in intramuscular ceramide level and a decrease in muscle protein synthesis associated with increased eIF2alpha phosphorylation. The accumulation of intramuscular lipids placed a lipid burden on mitochondria and created a disconnect between metabolic and regulating pathways in skeletal muscles of OR. In C2C12 cells, palmitate induced ceramide accumulation was associated with a decreased protein synthesis together with upregulated eIF2alpha phosphorylation. In conclusion, a reduced ability to expand adipose tissues was found in OR, reflecting a lower lipid buffering capacity. Muscle mitochondrial activity was affected in OR conferring a reduced ability to oxidize fatty acids entering the muscle cell. Hence, OR were more prone to ectopic muscle lipid accumulation than YR, leading to decreased muscle protein anabolism. This metabolic change is a potential therapeutic target to counter sarcopenic obesity. PMID- 25139158 TI - Esophagogastric dissociation reduces the re-operation rate for persistent gastroesophageal reflux in severely neurologically impaired children. AB - PURPOSE: In this study we want to demonstrate the effectiveness of the esophagogastric dissociation as a first level operation in treatment of the gastroesophageal reflux in severe neurologically impaired children, in term of a reduction of reoperation rate. METHODS: We divided patients operated from 1998 to 2005 in a group A, composed by children treated with fundoplication, and in a group AR, composed by the patients of group A who had a recurrence of reflux and that was treated with esophagogastric dissociation. Patients operated from 2005 to 2013 were selected on the basis of the severity of the neurological impairment and were divided in a group B, treated with fundoplication, and in a group C of more severe impaired children, treated with esophagogastric dissociation. Data regarding the complications of the A and C groups were analyzed with Fisher's test. RESULTS: We evaluated 63 patients: 34 (54%) in group A, 11 in group AR, 15 (23.6%) in group B, 14 (22.4%) in group C. The Fisher's test showed a non significant difference with a p value of 0.2. CONCLUSION: Despite of statistic result we believe that TOGD is a useful procedure as the first choice of surgical management in severe neurological impaired children affected by gastroesophageal reflux. PMID- 25139159 TI - A secreted protein with plant-specific cysteine-rich motif functions as a mannose binding lectin that exhibits antifungal activity. AB - Plants have a variety of mechanisms for defending against plant pathogens and tolerating environmental stresses such as drought and high salinity. Ginkbilobin2 (Gnk2) is a seed storage protein in gymnosperm that possesses antifungal activity and a plant-specific cysteine-rich motif (domain of unknown function26 [DUF26]). The Gnk2-homologous sequence is also observed in an extracellular region of cysteine-rich repeat receptor-like kinases that function in response to biotic and abiotic stresses. Here, we report the lectin-like molecular function of Gnk2 and the structural basis of its monosaccharide recognition. Nuclear magnetic resonance experiments showed that mannan was the only yeast (Saccharomyces cerevisiae) cell wall polysaccharide that interacted with Gnk2. Gnk2 also interacted with mannose, a building block of mannan, with a specificity that was similar to those of mannose-binding legume lectins, by strictly recognizing the configuration of the hydroxy group at the C4 position of the monosaccharide. The crystal structure of Gnk2 in complex with mannose revealed that three residues (asparagine-11, arginine-93, and glutamate-104) recognized mannose by hydrogen bonds, which defined the carbohydrate-binding specificity. These interactions were directly related to the ability of Gnk2 to inhibit the growth of fungi, including the plant pathogenic Fusarium spp., which were disrupted by mutation of arginine-93 or the presence of yeast mannan in the assay system. In addition, Gnk2 did not inhibit the growth of a yeast mutant strain lacking the alpha1,2 linked mannose moiety. These results provide insights into the molecular basis of the DUF26 protein family. PMID- 25139160 TI - Increased ratio of electron transport to net assimilation rate supports elevated isoprenoid emission rate in eucalypts under drought. AB - Plants undergoing heat and low-CO2 stresses emit large amounts of volatile isoprenoids compared with those in stress-free conditions. One hypothesis posits that the balance between reducing power availability and its use in carbon assimilation determines constitutive isoprenoid emission rates in plants and potentially even their maximum emission capacity under brief periods of stress. To test this, we used abiotic stresses to manipulate the availability of reducing power. Specifically, we examined the effects of mild to severe drought on photosynthetic electron transport rate (ETR) and net carbon assimilation rate (NAR) and the relationship between estimated energy pools and constitutive volatile isoprenoid emission rates in two species of eucalypts: Eucalyptus occidentalis (drought tolerant) and Eucalyptus camaldulensis (drought sensitive). Isoprenoid emission rates were insensitive to mild drought, and the rates increased when the decline in NAR reached a certain species-specific threshold. ETR was sustained under drought and the ETR-NAR ratio increased, driving constitutive isoprenoid emission until severe drought caused carbon limitation of the methylerythritol phosphate pathway. The estimated residual reducing power unused for carbon assimilation, based on the energetic status model, significantly correlated with constitutive isoprenoid emission rates across gradients of drought (r(2) > 0.8) and photorespiratory stress (r(2) > 0.9). Carbon availability could critically limit emission rates under severe drought and photorespiratory stresses. Under most instances of moderate abiotic stress levels, increased isoprenoid emission rates compete with photorespiration for the residual reducing power not invested in carbon assimilation. A similar mechanism also explains the individual positive effects of low-CO2, heat, and drought stresses on isoprenoid emission. PMID- 25139161 TI - Increased GDF9 and BMP15 mRNA levels in cumulus granulosa cells correlate with oocyte maturation, fertilization, and embryo quality in humans. AB - BACKGROUND: Oocyte secreted factors (OSFs), including growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), play an important role in the process of follicular development and oocyte maturation. Since OSFs are expressed in oocytes and cumulus granulosa cells, the aim of the present study was to explore whether the expression levels of GDF9 and BMP15 mRNAs in cumulus granulosa cells can be used as molecular markers for predicting oocyte developmental potential. METHODS: Cumulus cells of 2426 cumulus-oocyte complexes were collected from 196 female patients who underwent intracytoplasmic sperm injection (ICSI) and were used for mRNA detection on the egg retrieval day. Pearson correlation analysis was used to analyze the correlation between OSF expression and general physiological parameters. Partial correlation analysis was used to analyze the correlation between OSF expression and oocyte developmental potential. Covariance analysis was used to compare OSF expression among different groups. Receiver operating characteristic curves were used to examine the diagnostic value of GDF9 and BMP15 mRNA for predicting pregnancy. RESULTS: The expression levels of GDF9 and BMP15 mRNAs were significantly associated with age, body mass index (BMI), oocyte maturation, normal fertilization, and cleavage rate (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the group with high quality embryos were significantly higher than those in the group without high quality embryos (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the pregnancy group were significantly higher than those in the nonpregnancy group (P < 0.05). The cut-off value of GDF9 mRNA for predicting pregnancy was 4.82, with a sensitivity of 82% and a specificity of 64%. The cut-off value of BMP15 mRNA for predicting pregnancy was 2.60, with a sensitivity of 78% and a specificity of 52%. CONCLUSIONS: The expression levels of GDF9 and BMP15 mRNAs were closely associated with oocyte maturation, fertilization, embryo quality, and pregnancy outcome; therefore, GDF9 and BMP15 mRNAs in cumulus granulosa cells may be considered as new molecular markers for predicting oocyte developmental potential. PMID- 25139162 TI - Clinical symptoms predict poor overall survival in chronic-dialysis patients with renal cell carcinoma associated with end-stage renal disease. AB - OBJECTIVE: To evaluate which clinical symptoms predict the survival of patients with renal cell carcinoma associated with end-stage renal disease under chronic dialysis. METHODS: We retrospectively evaluated 401 patients with renal cell carcinoma associated with end-stage renal disease who underwent radical nephrectomy at our institute up through December 2012. Patients were divided into two groups: the symptomatic group and the incidental group, by diagnosis. We compared the clinicopathologic features and patient survival of the two groups and investigated prognostic factors using Cox multivariate analysis. RESULTS: Of the 401 patients, 124 (30.9%) were in the symptomatic group and 277 (69.0%) in the incidental group. The symptomatic group included more advanced tumors in terms of larger tumor size, higher stage and higher grade compared with the incidental group. The 5-year cancer-specific survival and overall survival of the symptomatic and incidental groups were 76.9 vs. 95.3% (P < 0.001) and 64.2 vs. 84.9% (P < 0.001), respectively. On multivariate analysis, the presence of symptoms, higher age, higher stage, diabetic nephropathy and longer hemodialysis duration were independent prognostic factors. CONCLUSIONS: Symptomatic detection was significantly associated with worse overall survival in patients with renal cell carcinoma associated with end-stage renal disease as well as sporadic renal cell carcinoma. The high incidence of renal cell carcinoma as well as the poor oncologic outcome in patients with longer dialysis therapy may suggest an important role for routine screening in these patients. PMID- 25139163 TI - Construction of predictive models for cancer-specific survival of patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin: results from a multicenter retrospective study. AB - OBJECTIVE: The aims of this study were to clarify the prognostic factors and to validate the bacillus Calmette-Guerin failure classification advocated by Nieder et al. in patients with non-muscle-invasive bladder cancer who had intravesical recurrence after bacillus Calmette-Guerin therapy. METHODS: Data from 402 patients who received intravesical bacillus Calmette-Guerin therapy between January 1990 and November 2011 were collected from 10 institutes. Among these patients, 187 with bacillus Calmette-Guerin failure were analyzed for this study. RESULTS: Twenty-nine patients (15.5%) were diagnosed with progression at the first recurrence after bacillus Calmette-Guerin therapy. Eighteen (62.1%) of them died of bladder cancer. A total of 158 patients were diagnosed with non-muscle invasive bladder cancer at the first recurrence after bacillus Calmette-Guerin therapy. Of them, 23 (14.6%) underwent radical cystectomy. No patients who underwent radical cystectomy died of bladder cancer during the follow-up. On multivariate analysis of the 135 patients with bladder preservation, the independent prognostic factors for cancer-specific survival were age (>=70 [P = 0.002]), tumor size (>=3 cm [P = 0.015]) and the Nieder classification (bacillus Calmette-Guerin refractory [P < 0.001]). In a subgroup analysis, the estimated 5 year cancer-specific survival rates in the groups with no positive, one positive and two to three positive factors were 100, 93.4 and 56.8%, respectively (P < 0.001). CONCLUSIONS: Patients with stage progression at the first recurrence after bacillus Calmette-Guerin therapy had poor prognoses. Three prognostic factors for predicting survival were identified and used to categorize patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin into three risk groups based on the number of prognostic factors in each one. PMID- 25139164 TI - Barriers to cervical cancer screening and follow-up care among Black Women in Massachusetts. AB - OBJECTIVE: To explore factors that might lead to delays in appropriate cervical cancer screening and diagnosis among Black women in Massachusetts. DESIGN: Qualitative using focus groups. SETTING: Hospitals, health centers, and community based organizations in Boston, Massachusetts. PARTICIPANTS: Sixty-four participants including Black, non-Hispanic women from the general population and cervical cancer survivors, community leaders in women's health, and health care providers. METHODS: Six focus groups. Data were analyzed using methods based on grounded theory. RESULTS: Findings from interviews revealed that inadequate information and education of providers and patients create barriers to appropriate screening and treatment practices for Black women. Fear, cultural beliefs, and compounding factors related to poverty, gender roles, and health system barriers create delays to screening and follow-up care. Also, unconscious bias, therapeutic delays, and miscommunication are important factors affecting continuity of care. CONCLUSION: These results suggest a need for comprehensive, culturally specific cervical cancer prevention education initiatives and interventions for Black women and strategies to improve patient-provider relationships. PMID- 25139166 TI - Mean sojourn time of preclinical gastric cancer in Korean men: a retrospective observational study. AB - OBJECTIVES: This retrospective cohort study aimed to estimate the mean sojourn time (MST) of preclinical gastric cancer in Korean men. METHODS: The subjects consisted of voluntary male screenees aged 40 to 69 years who underwent subsequent screening gastroscopies after testing negative at a baseline screening performed between January 2007 and December 2011. A new case was defined if gastric cancer cells were present in the biopsy specimens obtained from gastroscopy. The follow-up period was calculated as the number of person-years between the date of baseline screening gastroscopy and positive findings at a subsequent screening. The MST was calculated using transition rates of gastric cancer to determine the best screening interval. RESULTS: Of the 171 979 voluntary male screenees, 61 688 (36%) underwent subsequent screening gastroscopies between January 2007 and December 2011. A total of 91 incident cases were found during 19 598 598 person-years of follow-up. The MST of gastric cancer was 2.37 years (95% confidence intervals, 1.92 to 2.96), and those aged 40 to 49 years had a shorter MST than those 50 to 69 years did. CONCLUSIONS: These findings support the 2-year interval of screening recommended by the nationwide gastric cancer screening program in Korea. Further studies for the age-specific MST among women are needed. OBJECTIVES: This retrospective cohort study aimed to estimate the mean sojourn time (MST) of preclinical gastric cancer in Korean men. METHODS: The subjects consisted of voluntary male screenees aged 40 to 69 years who underwent subsequent screening gastroscopies after testing negative at a baseline screening performed between January 2007 and December 2011. A new case was defined if gastric cancer cells were present in the biopsy specimens obtained from gastroscopy. The follow-up period was calculated as the number of person years between the date of baseline screening gastroscopy and positive findings at a subsequent screening. The MST was calculated using transition rates of gastric cancer to determine the best screening interval. RESULTS: Of the 171 979 voluntary male screenees, 61 688 (36%) underwent subsequent screening gastroscopies between January 2007 and December 2011. A total of 91 incident cases were found during 19 598 598 person-years of follow-up. The MST of gastric cancer was 2.37 years (95% confidence intervals, 1.92 to 2.96), and those aged 40 to 49 years had a shorter MST than those 50 to 69 years did. CONCLUSIONS: These findings support the 2-year interval of screening recommended by the nationwide gastric cancer screening program in Korea. Further studies for the age-specific MST among women are needed. PMID- 25139165 TI - Cancer control programs in East Asia: evidence from the international literature. AB - Cancer is a major cause of mortality and morbidity throughout the world, including the countries of North-East and South-East Asia. Assessment of burden through cancer registration, determination of risk and protective factors, early detection and screening, clinical practice, interventions for example in vaccination, tobacco cessation efforts and palliative care all should be included in comprehensive cancer control programs. The degree to which this is possible naturally depends on the resources available at local, national and international levels. The present review concerns elements of cancer control programs established in China, Taiwan, Korea, and Japan in North-East Asia, Viet Nam, Thailand, Malaysia, and Indonesia as representative larger countries of South East Asia for comparison, using the published literature as a guide. While major advances have been made, there are still areas which need more attention, especially in South-East Asia, and international cooperation is essential if standard guidelines are to be generated to allow effective cancer control efforts throughout the Far East. PMID- 25139167 TI - Variations in the hospital standardized mortality ratios in Korea. AB - OBJECTIVES: The hospital standardized mortality ratio (HSMR) has been widely used because it allows for robust risk adjustment using administrative data and is important for improving the quality of patient care. METHODS: All inpatients discharged from hospitals with more than 700 beds (66 hospitals) in 2008 were eligible for inclusion. Using the claims data, 29 most responsible diagnosis (MRDx), accounting for 80% of all inpatient deaths among these hospitals, were identified, and inpatients with those MRDx were selected. The final study population included 703 571 inpatients including 27 718 (3.9% of all inpatients) in-hospital deaths. Using logistic regression, risk-adjusted models for predicting in-hospital mortality were created for each MRDx. The HSMR of individual hospitals was calculated for each MRDx using the model coefficients. The models included age, gender, income level, urgency of admission, diagnosis codes, disease-specific risk factors, and comorbidities. The Elixhauser comorbidity index was used to adjust for comorbidities. RESULTS: For 26 out of 29 MRDx, the c-statistics of these mortality prediction models were higher than 0.8 indicating excellent discriminative power. The HSMR greatly varied across hospitals and disease groups. The academic status of the hospital was the only factor significantly associated with the HSMR. CONCLUSIONS: We found a large variation in HSMR among hospitals; therefore, efforts to reduce these variations including continuous monitoring and regular disclosure of the HSMR are required. OBJECTIVES: The hospital standardized mortality ratio (HSMR) has been widely used because it allows for robust risk adjustment using administrative data and is important for improving the quality of patient care. METHODS: All inpatients discharged from hospitals with more than 700 beds (66 hospitals) in 2008 were eligible for inclusion. Using the claims data, 29 most responsible diagnosis (MRDx), accounting for 80% of all inpatient deaths among these hospitals, were identified, and inpatients with those MRDx were selected. The final study population included 703 571 inpatients including 27 718 (3.9% of all inpatients) in-hospital deaths. Using logistic regression, risk-adjusted models for predicting in-hospital mortality were created for each MRDx. The HSMR of individual hospitals was calculated for each MRDx using the model coefficients. The models included age, gender, income level, urgency of admission, diagnosis codes, disease-specific risk factors, and comorbidities. The Elixhauser comorbidity index was used to adjust for comorbidities. RESULTS: For 26 out of 29 MRDx, the c-statistics of these mortality prediction models were higher than 0.8 indicating excellent discriminative power. The HSMR greatly varied across hospitals and disease groups. The academic status of the hospital was the only factor significantly associated with the HSMR. CONCLUSIONS: We found a large variation in HSMR among hospitals; therefore, efforts to reduce these variations including continuous monitoring and regular disclosure of the HSMR are required. PMID- 25139169 TI - Analysis of the change of health status among the republic of Korea air force soldiers during military service. AB - OBJECTIVES: The aim of this study was to investigate whether the health status of Republic of Korea Air Force (ROKAF) soldiers changed after one year of military service. METHODS: We selected 483 ROKAF soldiers from the 11 749 recruits who participated in the 2011 physical examination. The selected soldiers underwent another physical examination in 2012 for advancement to senior airman. Data from 2011 and 2012 were merged. To collect data on lifestyle, a questionnaire was sent to all included subjects via the military intranet e-mail service. RESULTS: The percentage of recruits with an abnormal alanine transaminase level (normal range <40 IU/L) decreased from recruitment (13.7%) to the following year (2.7%). Moreover, the percentage of obese soldiers (body mass index >=25 kg/m(2)) decreased from recruitment (20.5%) to the following year (10.4%). There was a significant change in mean duration of exercise carried out each day before (0.8+/-1.3 hours) and after (1.0+/-0.7 hours) joining the ROKAF service. CONCLUSIONS: These ROKAF soldiers were generally in good health before and after joining the armed service. After one year of military service, the health status of most soldiers improved, especially with respect to body mass index and alanine transaminase level. OBJECTIVES: The aim of this study was to investigate whether the health status of Republic of Korea Air Force (ROKAF) soldiers changed after one year of military service. METHODS: We selected 483 ROKAF soldiers from the 11 749 recruits who participated in the 2011 physical examination. The selected soldiers underwent another physical examination in 2012 for advancement to senior airman. Data from 2011 and 2012 were merged. To collect data on lifestyle, a questionnaire was sent to all included subjects via the military intranet e-mail service. RESULTS: The percentage of recruits with an abnormal alanine transaminase level (normal range <40 IU/L) decreased from recruitment (13.7%) to the following year (2.7%). Moreover, the percentage of obese soldiers (body mass index >=25 kg/m2) decreased from recruitment (20.5%) to the following year (10.4%). There was a significant change in mean duration of exercise carried out each day before (0.8+/-1.3 hours) and after (1.0+/-0.7 hours) joining the ROKAF service. CONCLUSIONS: These ROKAF soldiers were generally in good health before and after joining the armed service. After one year of military service, the health status of most soldiers improved, especially with respect to body mass index and alanine transaminase level. PMID- 25139168 TI - The prevalence of cardiovascular disease risk factors and the Framingham Risk Score in patients undergoing percutaneous intervention over the last 17 years by gender: time-trend analysis from the Mayo Clinic PCI Registry. AB - OBJECTIVES: This study aims to investigate trends of cardiovascular disease (CVD) risk factor profiles over 17 years in percutaneous coronary intervention (PCI) patients at the Mayo Clinic. METHODS: We performed a time-trend analysis within the Mayo Clinic PCI Registry from 1994 to 2010. Results were the incidence and prevalence of CVD risk factors as estimate by the Framingham risk score. RESULTS: Between 1994 and 2010, 25 519 patients underwent a PCI. During the time assessed, the mean age at PCI became older, but the gender distribution did not change. A significant trend towards higher body mass index and more prevalent hypercholesterolemia, hypertension, and diabetes was found over time. The prevalence of current smokers remained unchanged. The prevalence of ever-smokers decreased among males, but increased among females. However, overall CVD risk according to the Framingham risk score (FRS) and 10-year CVD risk significantly decreased. The use of most of medications elevated from 1994 to 2010, except for beta-blockers and angiotensin converting enzyme inhibitors decreased after 2007 and 2006 in both baseline and discharge, respectively. CONCLUSIONS: Most of the major risk factors improved and the FRS and 10-year CVD risk declined in this population of PCI patients. However, obesity, history of hypercholesterolemia, hypertension, diabetes, and medication use increased substantially. Improvements to blood pressure and lipid profile management because of medication use may have influenced the positive trends. OBJECTIVES: This study aims to investigate trends of cardiovascular disease (CVD) risk factor profiles over 17 years in percutaneous coronary intervention (PCI) patients at the Mayo Clinic. METHODS: We performed a time-trend analysis within the Mayo Clinic PCI Registry from 1994 to 2010. Results were the incidence and prevalence of CVD risk factors as estimate by the Framingham risk score. RESULTS: Between 1994 and 2010, 25 519 patients underwent a PCI. During the time assessed, the mean age at PCI became older, but the gender distribution did not change. A significant trend towards higher body mass index and more prevalent hypercholesterolemia, hypertension, and diabetes was found over time. The prevalence of current smokers remained unchanged. The prevalence of ever-smokers decreased among males, but increased among females. However, overall CVD risk according to the Framingham risk score (FRS) and 10 year CVD risk significantly decreased. The use of most of medications elevated from 1994 to 2010, except for beta-blockers and angiotensin converting enzyme inhibitors decreased after 2007 and 2006 in both baseline and discharge, respectively. CONCLUSIONS: Most of the major risk factors improved and the FRS and 10-year CVD risk declined in this population of PCI patients. However, obesity, history of hypercholesterolemia, hypertension, diabetes, and medication use increased substantially. Improvements to blood pressure and lipid profile management because of medication use may have influenced the positive trends. PMID- 25139170 TI - Older adults' perception of chronic illness management in South Korea. AB - OBJECTIVES: Despite the recent emphasis on a patient-centered chronic care model, few studies have investigated its use in older adults in South Korea. We explored how older Korean adults perceive and cope with their chronic illness. METHODS: We conducted focus group interviews in Seoul, Korea in January 2010. Focus groups were formed by disease type (hypertension and type 2 diabetes) and gender using purposive sampling. Inclusion criteria were patients aged 60 and over who had been diagnosed with diabetes or hypertension and received care at a community health center for at least six months prior to participation. Interview data were analyzed through descriptive content analysis. RESULTS: Among personal factors, most participants felt overwhelmed when they received their diagnosis. However, with time and control of their acute symptoms using medication, their worry diminished and participants tended to denying being identified as a patient or sick person. Among socio-familial factors, participants reported experiencing stigma with their chronic illness and feeling it was a symbol of weakness. Instead of modifying their lifestyles, which might interfere with their social relationships, they resorted to only following their medicine regime prescribed by their doctor. Participants also reported feeling that their doctor only prescribed medications and acted in an authoritative and threatening manner to induce and reinforce participants' compliance with treatment. CONCLUSIONS: For successful patient-centered management of chronic illnesses, supportive environments that include family, friends, and healthcare providers should be established. OBJECTIVES: Despite the recent emphasis on a patient-centered chronic care model, few studies have investigated its use in older adults in South Korea. We explored how older Korean adults perceive and cope with their chronic illness. METHODS: We conducted focus group interviews in Seoul, Korea in January 2010. Focus groups were formed by disease type (hypertension and type 2 diabetes) and gender using purposive sampling. Inclusion criteria were patients aged 60 and over who had been diagnosed with diabetes or hypertension and received care at a community health center for at least six months prior to participation. Interview data were analyzed through descriptive content analysis. RESULTS: Among personal factors, most participants felt overwhelmed when they received their diagnosis. However, with time and control of their acute symptoms using medication, their worry diminished and participants tended to denying being identified as a patient or sick person. Among socio-familial factors, participants reported experiencing stigma with their chronic illness and feeling it was a symbol of weakness. Instead of modifying their lifestyles, which might interfere with their social relationships, they resorted to only following their medicine regime prescribed by their doctor. Participants also reported feeling that their doctor only prescribed medications and acted in an authoritative and threatening manner to induce and reinforce participants' compliance with treatment. CONCLUSIONS: For successful patient-centered management of chronic illnesses, supportive environments that include family, friends, and healthcare providers should be established. PMID- 25139171 TI - Effect of DOCA/salt hypertension on CRF expression in the amygdala and the autonomic stress response in conscious rats. AB - The effects of DOCA/salt treatment on amygdala-area CRF gene expression and the autonomic response to air jet stress (AJS) were evaluated in conscious male Sprague Dawley (SD) rats. Fifteen days of DOCA/salt treatment significantly increased resting arterial pressure (AP), decreased resting heart rate (HR) and significantly reduced regional CRF mRNA compared to controls (23+/-7% vs. 100+/ 26%) independent of changes in regional CRF receptor expression. Twenty min of AJS elicited a rise in AP (~15mmHg) that was similar in both DOCA/salt animals (n=11) and controls (n=6). Alternatively, increases in HR were significantly different in the DOCA/salt animals compared to controls; including one group of DOCA/salt animals (n=5) which responded with an attenuated HR response at the onset of AJS (low-responders) and a second group (n=6) which demonstrated an elevated HR response to AJS (high-responders), specifically during the last 10min of AJS. The divergent HR responses to AJS in the DOCA/salt animals were linked to differences in resting heart rate variability. During recovery HR returned to baseline within 10min in both control and the low responder DOCA group but indicators of spontaneous baroreflex gain only increased significantly in controls. HR in the high-responder DOCA animals did not return to baseline during the same period. These results show that DOCA/salt treatment triggers downregulation of CRF gene expression in the region of the amygdala and significantly alters the HR response to acute stress but does not alter the pressor response to stress compared to normotensive controls. PMID- 25139172 TI - Potential application of non-flavonoid phenolics in diabetes: antiinflammatory effects. AB - Polyphenols are members of a very large family of plant-derived compounds that may have beneficial effects on human health, and thus their study has become an increasingly important area of human nutrition research. Considering that it is increasingly accepted that chronic sub-acute inflammation plays an important role in the development of insulin resistance and of diabetes in animals and in humans, the aim of the present review is to compile information concerning the anti-inflammatory effects of non-flavonoid polyphenols on diabetes prevention and/or treatment. Most of these studies have been carried out with different cultured cells and using animal models displaying different types of diabetes, such as diabetes induced by streptozotocin or streptozotocin-nicotinamide, genetic diabetes or diabetes induced by high-fat feeding. In general terms, non flavonoid polyphenols reduce the production of inflammatory mediators, such as IL 1beta, IL-8, MCP-1, COX-2 or iNOS in these animal models of diabetes. This effect is accompanied in the vast majority of these studies by improved insulin action. In addition, some of the non-flavonoid polyphenols are also able to ameliorate or prevent several pathological alterations associated with the development of diabetes, such as nephropathy, cardiopathy or retinopathy. Very little information has been reported with regard to human studies to date. Thus, new studies are needed to confirm if the beneficial effects observed in preclinical studies can apply to human beings. PMID- 25139173 TI - Ulipristal acetate resembles mifepristone in modulating human fallopian tube function. AB - STUDY QUESTION: Do ulipristal acetate (UPA) and mifepristone have an effect on ciliary beat frequency and muscular contractions in the human Fallopian tube? SUMMARY ANSWER: UPA, in resemblance to mifepristone, inhibits ciliary beat and muscular contraction of the human Fallopian tube, probably through an agonistic effect on the tubal progesterone receptor. WHAT IS KNOWN ALREADY: UPA, like mifepristone, acts as an emergency contraceptive mainly by inhibiting ovulation. Little is known about its effects on tubal function. STUDY DESIGN, SIZE, DURATION: This was an in vitro experimental study using Fallopian tube samples collected from 11 women undergoing hysterectomy for benign non-tubal gynaecological conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS: The tubal epithelium and longitudinal smooth muscle fibres were isolated, cultured and treated with UPA at graded concentrations of 0, 20, 200 and 2000 ng/ml, and mifepristone at graded concentrations of 0, 300, 3000 and 30 000 ng/ml, respectively. After treatment, ciliary beat frequency was determined using a photometric method. Basal tone, amplitude and frequency of muscular contraction were recorded through a force transducer. The mRNA expression of progesterone receptor (total and PR-B isoform), glycodelin and adrenomedullin were determined by real-time quantitative PCR. MAIN RESULTS AND THE ROLE OF CHANCE: There was an overall dose-dependent suppressive effect on ciliary beat frequency (P < 0.0001) after treatment with UPA at all concentrations and with mifepristone at 3000 ng/ml or above. The basal tone, amplitude and frequency of muscular contractions were significantly reduced (P < 0.05) after treatment with UPA at 200 ng/ml or above, and with mifepristone at 3000 ng/ml or above. UPA treatment at 200 ng/ml or above significantly up-regulated the mRNA expression of progesterone receptor and glycodelin and down-regulated the mRNA expression of adrenomedullin in Fallopian tube tissue (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Whether or not the tubal effect may translate into additional mechanisms for contraceptive action in vivo is uncertain. WIDER IMPLICATIONS OF THE FINDINGS: The clinical relevance of UPA with regard to contraceptive activity is worthy of further exploration. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a Seed Fund from the Centre of Reproduction, Development and Growth, Faculty of Medicine, the University of Hong Kong. All authors have no competing interest to declare. PMID- 25139176 TI - Fast synthesis of high-quality reduced graphene oxide at room temperature under light exposure. AB - An approach of presenting new reducing reagents, sodium-benzophenone (Na-B) or Na B in the presence of the hydrazine (Na-B-H) system under light exposure could produce rGOs with/without N-doping at room temperature in both the solution phase and on a solid substrate. Benzophenone activated those solutions acting as a photosensitizer under light. It was assumed that the newly generated radical anions with electrons from Na-B under light can reduce GO to rGO sheets (rGONa B1). In addition, the Na-B-H system can allow a higher degree of reduction with the doping of nitrogen atoms by the introduction of hydrazine to produce radical anions and electrons with a sodium hydrazide complex, which helps decrease the sheet resistance of the as-made rGONa-B-H2. The excellent properties (very low oxygen content (C/O ~16.2), and low sheet resistance (~130 Omega square(-1))) of the rGOs were confirmed by XPS, XRD, IR, Raman spectroscopy, TGA, wettability, and sheet resistance measurements. High-quality rGO films on flexible substrates could be prepared by directly immersing the GO films in these solutions for several minutes. PMID- 25139174 TI - The effect of metformin treatment in vivo on acute and long-term energy metabolism and progesterone production in vitro by granulosa cells from women with polycystic ovary syndrome. AB - STUDY QUESTION: What are the consequences of polycystic ovary syndrome (PCOS) pathology and metformin-pretreatment in vivo in women with PCOS on the metabolism and steroid production of follicular phenotype- and long-term cultured-granulosa cells (GC)? SUMMARY ANSWER: PCOS pathology significantly compromised glucose metabolism and the progesterone synthetic capacity of follicular- and long-term cultured-GCs and the metabolic impact of PCOS on GC function was alleviated by metformin-pretreatment in vivo. WHAT IS KNOWN ALREADY: Granulosa cells from women with PCOS have been shown to have an impaired insulin-stimulated glucose uptake and lactate production in vitro. However, these results were obtained by placing GCs in unphysiological conditions in culture medium containing high glucose and insulin concentrations. Moreover, existing data on insulin-responsive steroid production in vitro by PCOS GCs vary. STUDY DESIGN, SIZE AND DURATION: Case control experimental research comparing glucose uptake, pyruvate and lactate production and progesterone production in vitro by GCs from three aetiological groups, all undergoing IVF; healthy control women (Control, n = 12), women with PCOS treated with metformin in vivo (Metformin, n = 8) and women with PCOS not exposed to metformin (PCOS, n = 8). The study was conducted over a period of 3 years between 2007 and 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Rotterdam criteria were used for the diagnosis of PCOS; all subjects were matched for age, BMI and baseline FSH. Individual patient cultures were undertaken with cells incubated in a validated, physiological, serum-free culture medium containing doses of 0-6 mM glucose and 0-100 ng/ml insulin for 6 h and 144 h to quantify the impact of treatments on acute and long-term metabolism, respectively, and progesterone production. The metabolite content of spent media was measured using spectrophotometric plate reader assay. The progesterone content of spent media was measured by enzyme-linked immunosorbent assay. Viable GC number was quantified after 144 h of culture by the vital dye Neutral Red uptake assay. MAIN RESULTS AND THE ROLE OF CHANCE: Granulosa cells from women with PCOS pathology revealed reduced pyruvate production and preferential lactate production in addition to their reduced glucose uptake during cultures (P < 0.05). Metformin pretreatment alleviated this metabolic lesion (P < 0.05) and enhanced cell proliferation in vitro (P < 0.05), but cells retained a significantly reduced capacity for progesterone synthesis compared with controls (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Although significant treatment effects were detected in this small cohort, further studies are required to underpin the molecular mechanisms of the effect of metformin on GCs. WIDER IMPLICATIONS OF THE FINDINGS: The individual patient culture strategy combined with multifactorial experimental design strengthens the biological interpretation of the data. Collectively, these results support the notion that there is an inherent impairment in progesterone biosynthetic capacity of the GCs from women with PCOS. The positive, acute metabolic effect and the negative long-term steroidogenic effect on GCs following metformin exposure in vivo may have important implications for follicular development and luteinized GC function when the drug is used in clinical practice. STUDY FUNDING/COMPETING INTERESTS: No competing interests. This work was supported by the UK Medical Research Council Grant Reference number G0800250. PMID- 25139177 TI - Retroperitoneal laparoscopic reimplantation of the left renal vein for nutcracker syndrome. AB - OBJECTIVE: To describe the feasibility of retroperitoneal laparoscopic reimplantation of the left renal vein (LRV) for nutcracker syndrome (NCS). PATIENTS AND METHODS: Two patients with NCS underwent the surgery. Both patients complained of gross hematuria and flank discomfort that could not be relieved by resting. They were placed in a supine position and 5 ports were placed in the right abdominal wall. The procedures were performed with a retroperitoneal approach. The LRV was transected and then reimplanted into the distal inferior vena cava. RESULTS: The procedures were performed successfully without any major complications. The total operation time was 105 and 120 min, respectively. Hematuria and flank discomfort were resolved after the surgery. Ultrasonography revealed a patent lumen without compression. CONCLUSIONS: Retroperitoneal laparoscopic reimplantation of the LRV appears to be a feasible procedure with satisfactory short-term outcomes. PMID- 25139175 TI - Severe teenage acne and risk of endometriosis. AB - STUDY QUESTION: Is there a relationship between severe teenage acne and endometriosis? SUMMARY ANSWER: Endometriosis is positively associated with severe teenage acne. WHAT IS KNOWN ALREADY: No studies have specifically explored a possible association between severe acne in adolescence and risk of endometriosis. STUDY DESIGN, SIZE, DURATION: This prospective cohort study used data collected from 88 623 female nurses from September 1989 to June 2009 as part of the Nurses' Health Study II (NHS II) cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Regression models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) for endometriosis among women with and without severe teenage acne. Multivariate models were adjusted for established risk factors of endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4 382 laparoscopically confirmed endometriosis cases were documented during 1 132 272 woman-years of follow-up. Compared with women without a history of severe teenage acne, women who had severe teenage acne had a 20% increased risk of endometriosis (HR = 1.20, 95% CI: 1.08-1.32). The association was not affected by adjusting for use of tetracycline or isotretinoin. LIMITATIONS AND REASONS FOR CAUTION: The HR is likely to be underestimated since we only included endometriosis cases confirmed by laparoscopy. Although geographically diverse, the NHS II cohort is primarily Caucasian, which may limit generalization to more ethnically diverse populations. WIDER IMPLICATIONS OF THE STUDY: The results of this study suggest that severe teenage acne is associated with an increased risk of endometriosis. As a visible and non-invasive clinical indicator, severe teenage acne may be useful for early detection of endometriosis. We bring this counter-intuitive association to the attention of clinicians for the benefit of the patient and an early diagnosis of endometriosis. STUDY FUNDING/COMPETING INTEREST: This study was funded by research grant CA176726 from the National Institute of Health. M.K. is supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078). The funding agencies had no role in the design of the study, in the analysis and interpretation of the data, in the writing of the report or in the decision to submit the paper for publication. PMID- 25139178 TI - The (lack of) effect of alprazolam on eating behavior in anorexia nervosa: a preliminary report. AB - OBJECTIVE: Anxiety is a prominent symptom in anorexia nervosa (AN), and higher pre-meal anxiety has been associated with lower caloric intake. Yet, the causal relationship has not been assessed. We proposed that reducing anxiety with a short acting benzodiazepine would increase caloric intake among individuals with AN. METHOD: In a randomized, double-blind, placebo controlled cross-over study, we administered alprazolam 0.75 mg to inpatients with AN (n = 17) and assessed caloric intake in a laboratory test meal. Within-subject differences in caloric intake, anxiety, and fatigue were compared between alprazolam and placebo days. RESULTS: Caloric intake did not differ on alprazolam versus placebo (t(15) = 1.72, p = .11). Alprazolam did not reduce anxiety, but was associated with increased fatigue. DISCUSSION: This study was not able to evaluate the causal role of anxiety in meal intake among individuals with AN, as alprazolam did not alter anxiety symptoms. These data further suggest that the therapeutic role for short-acting benzodiazepines in AN is likely limited. PMID- 25139180 TI - Photoinduced energy transfer from poly(N-vinylcarbazole) to tricarbonylchloro (2,2'-bipyridyl)rhenium(I). AB - This work investigates the photoinduced energy transfer from poly(N vinylcarbazole) (PVK), as a donor material, to fac-(2,2'-bipyridyl)Re(CO)3Cl, as a catalyst acceptor, for its potential application towards CO2 reduction. Photoluminescence quenching experiments reveal dynamic quenching through resonance energy transfer in solid donor/acceptor mixtures and in solid/liquid systems. The bimolecular reaction rate constant at solution-film interfaces for the elementary reaction of the excited state with the quencher material could be determined as 8.8(+/-1.4)*10(11) L mol(-1) s(-1) by using Stern-Volmer analysis. This work shows that PVK is an effective and cheap absorber material that can act efficiently as a redox photosensitizer in combination with fac-(2,2' bipyridyl)Re(CO)3Cl as a catalyst acceptor, which might lead to possible applications in photocatalytic CO2 reduction. PMID- 25139179 TI - In silico model-based inference: a contemporary approach for hypothesis testing in network biology. AB - Inductive inference plays a central role in the study of biological systems where one aims to increase their understanding of the system by reasoning backwards from uncertain observations to identify causal relationships among components of the system. These causal relationships are postulated from prior knowledge as a hypothesis or simply a model. Experiments are designed to test the model. Inferential statistics are used to establish a level of confidence in how well our postulated model explains the acquired data. This iterative process, commonly referred to as the scientific method, either improves our confidence in a model or suggests that we revisit our prior knowledge to develop a new model. Advances in technology impact how we use prior knowledge and data to formulate models of biological networks and how we observe cellular behavior. However, the approach for model-based inference has remained largely unchanged since Fisher, Neyman and Pearson developed the ideas in the early 1900s that gave rise to what is now known as classical statistical hypothesis (model) testing. Here, I will summarize conventional methods for model-based inference and suggest a contemporary approach to aid in our quest to discover how cells dynamically interpret and transmit information for therapeutic aims that integrates ideas drawn from high performance computing, Bayesian statistics, and chemical kinetics. PMID- 25139181 TI - Robust pro-inflammatory and lesser anti-inflammatory immune responses during primary simian varicella virus infection and reactivation in rhesus macaques. AB - Simian varicella virus (SVV) infection of non-human primates models human varicella zoster virus (VZV) infection. Assessment of cell signaling immune responses in monkeys after primary SVV infection, after immunosuppression and during reactivation revealed strong pro-inflammatory responses and lesser anti inflammatory components during varicella and reactivation. Pro-inflammatory mediators elevated during varicella included interferon-gamma (IFN-gamma), interleukin (IL)-6, monocyte chemoattractant protein (MCP-1), interferon inducible T-cell alpha chemoattractant protein (I-TAC), interferon processing protein (IP-10), and anti-inflammatory interleukin-1 Receptor antagonist (IL 1Ra). After immunosuppression and at reactivation, levels of pro-inflammatory mediators MCP-1, eotaxin, IL-6, IL-8, MIF, RANTES (regulated-on-activation normal T-cell expressed and secreted), and HGF (hepatocyte growth factor) were elevated, as was the anti-inflammatory mediator IL-1Ra. Characterization of cytokine, chemokine and growth factor responses during different stages of varicella virus infection will facilitate immunotherapeutic and vaccine strategies. PMID- 25139182 TI - Review of West Nile virus epidemiology in Italy and report of a case of West Nile virus encephalitis. AB - West Nile virus (WNV) is a flavivirus that causes neurological disorders in less than 1 % of infected subjects. Human cases of WNV-associated fever and/or neurological disorders have been reported in Italy since 2008. The first outbreak occurred in the northeastern region of Italy surrounding the Po River and was caused by the Po River lineage 1 strain, and since then, WNV infections have been reported in several regions of central Italy. Although the virus is highly genetically conserved, stochastic mutations in its genome may lead to the emergence of new strains, as was observed in Italy in 2011 with the identification of two new lineage 1 strains, the WNV Piave and WNV Livenza strains. To help further define WNV epidemiology in Italy, we describe a case of an Italian man living in the Po River area who developed fatal encephalitis in 2009 due to infection with the WNV Piave strain. This finding supports the notion that the Piave strain has been circulating in this area of Italy for 2 years longer than was previously believed. PMID- 25139184 TI - Revealing the distribution of the atoms within individual bimetallic catalyst nanoparticles. AB - To be able to correlate the catalytic properties of nanoparticles with their structure, detailed knowledge about their make-up on the atomic level is required. Herein, we demonstrate how atom-probe tomography (APT) can be used to quantitatively determine the three-dimensional distribution of atoms within a Au@Ag nanoparticle with near-atomic resolution. We reveal that the elements are not evenly distributed across the surface and that this distribution is related to the surface morphology and residues from the particle synthesis. PMID- 25139183 TI - Frequent utilization of the emergency department for acute heart failure syndrome: a population-based study. AB - BACKGROUND: Although most research on patients with acute heart failure syndrome (AHFS) has focused on readmissions, this may provide an incomplete picture of health-care utilization. We examined the proportion and characteristics of patients with frequent emergency department (ED) visits for AHFS and associated health-care utilization. METHODS AND RESULTS: A retrospective cohort study of adults with at least 1 ED visit for AHFS between 2010 and 2011 was performed, derived from population-based multipayer data of state ED and inpatient databases for 2 large and diverse states, California and Florida. The analytic sample comprised 113 033 patients with 175 491 ED visits for AHFS. During the 1-year follow-up period, 30.8% of patients had >=2 (frequent) visits, accounting for 55.4% (95% confidence interval, 55.2-55.5%) of all ED visits for AHFS. In the multivariable model, significant predictors of frequent ED visits were non Hispanic black race, Hispanic ethnicity, Medicaid insurance, and lower median household income (all P<0.001). At the visit level, patients with frequent ED visits accounted for 55.0% (95% confidence interval, 54.8-5.3%) of all AHFS hospitalizations via ED. Total charges for AHFS were $3.08 billion (95% confidence interval, $3.03-3.14 billion) in Florida alone; patients with frequent ED visits accounted for 53.3% of total charges (95% confidence interval, 53.2 53.3%). CONCLUSIONS: In this large cohort study, we found that one third (31%) of ED patients with AHFS had frequent ED visits for this condition and that minority race/ethnicity and lower socioeconomic status were associated with frequent ED visits. Individuals with frequent ED visits accounted for the majority of ED visits, hospitalizations, and hospital charges. PMID- 25139186 TI - Identifying soluble mediators of nuclear receptor and insulin signaling may enhance noninvasive diagnosis of fibrosis in Fatty liver disease. PMID- 25139185 TI - Epicardial adipose tissue thickness, flow-mediated dilatation of the brachial artery, and carotid intima-media thickness: Associations in rheumatoid arthritis patients. AB - AIM: The purpose of this work was to evaluate epicardial adipose tissue (EAT), carotid intima-media thickness (CIMT), and flow-mediated dilatation (FMD) of the brachial artery in rheumatoid arthritis (RA) patients using ultrasonographic methods. Interrelationships between these three parameters in RA patients were also investigated. METHODS: EAT thickness, CIMT, and FMD were measured by ultrasonography. We measured the disease activity score (DAS28), health assessment questionnaire (HAQ) score, and C-reactive protein (CRP) levels. Spearman or Pearson correlation analysis was used to evaluate the association between clinical findings, CIMT, FMD, and EAT. RESULTS: A total of 90 RA patients [19 men, mean age 54 years (range 21-76 years)] and 59 age- and gender-matched control subjects [17 men, mean age 54 years (range 26-80 years)] were included in the study. Patients with RA had a mean 4.34 DAS28 points (range 0-40 points) and the mean duration of the disease was 77.1 months (range 1-360 months). We found that RA patients had thicker EAT (7.7 +/- 1.7 mm vs 6.2 +/- 1.8 mm, p < 0.001), increased CIMT [0.9 (0.5-1.2) mm vs 0.6 (0.4-0.9) mm, p < 0.001], and decreased FMD values [5.7 % (- 23.5 to 20 %) vs. 8.5 % (- 4.7 to 22.2 %), p = 0.028] when compared to control subjects. CRP levels were significantly higher in the RA group [0.81 (range 0.1-13.5) vs 0.22 (range 0.05-12), p < 0.001]. EAT thickness was negatively correlated with FMD (r = - 0.26, p < 0.001) and positively correlated with CIMT values (r = 0.52, p < 0.001). CIMT also negatively correlated with FMD (r = - 0.29, p < 0.001). CONCLUSION: EAT can be simply measured by echocardiography and correlated with FMD and CIMT. It can be used as a first-line measurement for estimating burden of atherosclerosis in RA patients. PMID- 25139188 TI - Human evolution: making the most of damage. PMID- 25139189 TI - Pathogen genetics: temporary survival of the fittest? PMID- 25139187 TI - Using next-generation sequencing to isolate mutant genes from forward genetic screens. AB - The long-lasting success of forward genetic screens relies on the simple molecular basis of the characterized phenotypes, which are typically caused by mutations in single genes. Mapping the location of causal mutations using genetic crosses has traditionally been a complex, multistep procedure, but next generation sequencing now allows the rapid identification of causal mutations at single-nucleotide resolution even in complex genetic backgrounds. Recent advances of this mapping-by-sequencing approach include methods that are independent of reference genome sequences, genetic crosses and any kind of linkage information, which make forward genetics amenable for species that have not been considered for forward genetic screens so far. PMID- 25139190 TI - Population genomics: a new window into the genetics of complex diseases. PMID- 25139193 TI - The effect of protein PEGylation on physical stability in liquid formulation. AB - The presence of micron aggregates in protein formulations has recently attracted increased interest from regulatory authorities, industry, and academia because of the potential undesired side effects of their presence. In this study, we characterized the micron aggregate formation of hen egg-white lysozyme (Lyz) and its diPEGylated (5 kDa) analog as a result of typical handling stress conditions. Both proteins were subjected to mechanical stress in the absence and presence of silicone oil (SO), elevated temperatures, and freeze-thaw cycles. Flow imaging microscopy showed that PEGylated Lyz formed approximately half as many particles as Lyz, despite its lower apparent thermodynamic stability and more loose protein fold. Further characterization showed that the PEGylation led to a change from attractive to repulsive protein-protein interactions, which may partly explain the reduced particle formation. Surprisingly, the PEGylated Lyz adsorbed an order of magnitude faster onto SO, despite being much larger in size, as determined by small-angle X-ray scattering and dynamic light scattering measurements. Thus, PEGylation may significantly reduce, but not prevent, micron aggregate formation of a protein during typical handling stresses. PMID- 25139191 TI - Carbachol-induced colonic mucus formation requires transport via NKCC1, K+ channels and CFTR. AB - The colonic mucosa protects itself from the luminal content by secreting mucus that keeps the bacteria at a distance from the epithelium. For this barrier to be effective, the mucus has to be constantly replenished which involves exocytosis and expansion of the secreted mucins. Mechanisms involved in regulation of mucus exocytosis and expansion are poorly understood, and the aim of this study was to investigate whether epithelial anion secretion regulates mucus formation in the colon. The muscarinic agonist carbachol was used to induce parallel secretion of anions and mucus, and by using established inhibitors of ion transport, we studied how inhibition of epithelial transport affected mucus formation in mouse colon. Anion secretion and mucin exocytosis were measured by changes in membrane current and epithelial capacitance, respectively. Mucus thickness measurements were used to determine the carbachol effect on mucus growth. The results showed that the carbachol-induced increase in membrane current was dependent on NKCC1 co transport, basolateral K(+) channels and Cftr activity. In contrast, the carbachol-induced increase in capacitance was partially dependent on NKCC1 and K(+) channel activity, but did not require Cftr activity. Carbachol also induced an increase in mucus thickness that was inhibited by the NKCC1 blocker bumetanide. However, mice that lacked a functional Cftr channel did not respond to carbachol with an increase in mucus thickness, suggesting that carbachol induced mucin expansion requires Cftr channel activity. In conclusion, these findings suggest that colonic epithelial transport regulates mucus formation by affecting both exocytosis and expansion of the mucin molecules. PMID- 25139194 TI - Highly stretchable and conductive silver nanowire thin films formed by soldering nanomesh junctions. AB - Silver nanowires (AgNWs) have been widely used for stretchable and foldable conductors due to their percolating network nanostructure. To enhance the mechanical strength of AgNW thin films under extreme stretching conditions, in this study, we utilize a simple chemical reaction to join AgNW network connections. Upon applying a reactive ink over AgNW thin films, silver nanoparticles are preferentially generated over the nanowire junctions and solder the nanomesh structures. The soldered nanostructure reinforces the conducting network and exhibits no obvious change in electrical conductivity in the stretching or rolling process with elongation strains up to 120%. Several examples are also demonstrated to show potential applications of this material in stretchable electronic devices. PMID- 25139192 TI - Effect of high-fat diet on rat myometrium during pregnancy-isolated myometrial mitochondria are not affected. AB - Laboring women with elevated body mass index (BMI) have an increased risk of inefficient uterine labor contractions, and despite the significance of mitochondria in the production of energy to drive uterine contractions, mitochondrial function in the myometrium with reference to the BMI has not been explored. The objective of this study was to determine whether obesity prior to and during gestation affects oxidative capacity and/or morphology of mitochondria in the myometrium at term in an animal model. Rat dams were fed for 47 days prior to impregnation and during gestation with either (1) a regular chow diet, (2) a low-fat high-carbohydrate diet, or (3) a high-fat low-carbohydrate diet (n = 10 in each group). On day 20 of gestation, corresponding to term pregnancy, total hysterectomy was performed with subsequent examination of the function and morphology of myometrial mitochondria. Body composition was regularly assessed by quantitative magnetic resonance imaging, and blood sampling was done prior to diet assignment, impregnation, and hysterectomy. Dams on the high-fat low carbohydrate diet achieved higher fat percentage compared to rats on the regular chow diet (p < 0.05). Maximal oxygen consumption, phosphate/oxygen ratio, or the amount of mitochondria per gram of myometrium did not differ between the three feeding groups. Electron microscopic examinations did not reveal any morphological differences in mitochondria between groups; however, a previously undescribed subsarcolemmal localization of the mitochondria in the myocyte was identified. We did not find evidence of altered myometrial mitochondrial function or morphology in this animal model of obesity prior to and during pregnancy. PMID- 25139195 TI - Lack of effect of the glucagon-like peptide-1 receptor agonist liraglutide on psoriasis in glucose-tolerant patients--a randomized placebo-controlled trial. AB - BACKGROUND: It has been proposed that glucagon-like peptide-1 receptor (GLP-1R) agonists used for the treatment of patients with type 2 diabetes might also improve their psoriasis. OBJECTIVE: To assess the efficacy and safety of the GLP 1R agonist liraglutide in glucose-tolerant patients with plaque psoriasis. METHODS: A total of 20 obese (body mass index > 25 kg/m(2)), glucose-tolerant patients with plaque psoriasis (psoriasis area and severity index (PASI) of at least 8) were randomized 1:1 to once-daily subcutaneous injections with liraglutide or placebo for an 8-week period. The primary end points were improvement in PASI and dermatology life quality index (DLQI). Secondary end points included changes in weight and high sensitive C-reactive protein (hsCRP) levels, as well as adverse events. RESULTS: After 8 weeks of treatment, no significant change in PASI was found in the liraglutide group (mean+/-standard deviation: -2.6 +/- 2.1) compared with the placebo group (-1.3 +/- 2.4) (P = 0.228). No difference in DLQI was observed between the groups [-2.5 +/- 4.4 (liraglutide) vs. -3.7 +/- 4.8 (placebo); P = 0.564]. HsCRP did not change in any of the groups (0.26 +/- 1 (placebo) vs. 0.25 +/- 2.2 (liraglutide); P = 0.992). Liraglutide treatment resulted in a bodyweight loss of 4.7 +/- 2.5 kg compared with 1.6 +/- 2.7 kg in the placebo group (P = 0.014) accompanied by decreased cholesterol levels. No serious adverse events occurred during the 8-week observation period. The most common complaint was transient nausea, which occurred in 45% of the liraglutide-treated patients but in none from the placebo group. CONCLUSION: Liraglutide treatment for 8 weeks did not significantly change PASI, DLQI, or hsCRP in a small group of glucose-tolerant obese patients with plaque psoriasis compared with placebo. A significant weight loss and decrease in cholesterol levels was observed in liraglutide-treated patients. PMID- 25139196 TI - Neoadjuvant chemotherapy for different molecular breast cancer subtypes: a retrospective study in Russian population. AB - The aim of this retrospective study was to evaluate the objective clinical response (cOR), pathological complete response (pCR), and progression-free survival (PFS) in 231 Russian patients with four subtypes of breast cancer treated with neoadjuvant chemotherapy. About 130 (56.3 %) patients received anthracycline-based, 56 (24.2 %) capecitabine-containing (CAX), 28 (12.1 %) taxotere and 17 (7.4 %) non-anthracycline-containing chemotherapy regimens at the Tomsk Cancer Research Institute between 2000 and 2010. Tumors were subtyped according to the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) immunohistochemical data. The majority of tumors (48.9 %) were ER+/PR+ and HER2-negative (HR+/HER2-), 10.4 % were ER+ PR+ and HER2-positive (HR+/HER2+), 9.1 % were ER-/PR- and HER2-overexpressed (HER2-enriched) and 31.6 % were ER-/PR- and HER2-negative (triple negative). Both cOR and pCR were significantly higher in the triple-negative tumors compared to the other subtypes (P = 0.021 and P = 0.033, respectively). Among the four chemotherapy regimens, only CAX regimen had a predictive value for cOR (HR 2.30, 95 % CI 1.16-4.58, P = 0.009). Multivariate regression analysis showed that the triple-negative subtype (HR 2.54, 95 % CI 1.06-1.42, P = 0.011) and CAX regimen (HR 3.01, 95 % CI 1.01-1.46, P = 0.002) were significantly associated with cOR. No association between patient's PFS and a tumor subtype was observed. However, there was a trend for a prolonged PFS among patients with cOR (P = 0.056). Our data indicate a potentially better prognosis for triple-negative breast cancer patients if treated with the CAX neoadjuvant regimen. PMID- 25139198 TI - Re: Eric A. Klein, Matthew R. Cooperberg, Cristina Magi-Galluzzi, et al. A 17 gene assay to predict prostate cancer aggressiveness in the context of gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur urol 2014;66:550-60. PMID- 25139197 TI - Preoperative Prostate-specific Antigen Isoform p2PSA and Its Derivatives, %p2PSA and Prostate Health Index, Predict Pathologic Outcomes in Patients Undergoing Radical Prostatectomy for Prostate Cancer: Results from a Multicentric European Prospective Study. AB - BACKGROUND: Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are potential candidates for radical prostatectomy (RP). New biomarkers would be welcome. OBJECTIVE: To test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology. DESIGN, SETTING, AND PARTICIPANTS: An observational prospective multicentre European study was performed in 489 consecutive PCa patients treated with RP. Total PSA (tPSA), free PSA (fPSA), and p2PSA levels were determined. The %fPSA [(fPSA / tPSA) * 100], %p2PSA [(p2PSA pg/ml) / (fPSA ng/ml * 1000) * 100], and PHI [(p2PSA / fPSA) * ?tPSA] were calculated. INTERVENTION: Open or robot-assisted RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression models were fitted to test the predictors of pT3 stage and/or pathologic Gleason score (GS) >=7 and to determine their predictive accuracy. The base multivariable model included tPSA, digital rectal examination, biopsy GS, and percentage of positive biopsy cores. Decision curve analysis provided an estimate of the net benefit obtained using p2PSA, %p2PSA, or PHI. RESULTS AND LIMITATIONS: Overall, 344 patients (70%) were affected by pT3 disease or pathologic GS >=7; pT3 disease and pathologic GS >=7 were present in 126 patients (26%). At univariable analysis, p2PSA, %p2PSA, and PHI were significant predictors of pT3 disease and/or pathologic GS >=7 (all p <= 0.001). The inclusion of PHI significantly increased the accuracy of the base multivariable model by 2.3% (p=0.003) and 2.4% (p=0.01) for the prediction of pT3 disease and/or pathologic GS >=7, respectively. However, at decision curve analysis, models including PHI did not show evidence of a greater clinical net benefit. CONCLUSIONS: Both %p2PSA and PHI are significant predictors of unfavourable PCa characteristics at final pathology; however, %p2PSA and PHI did not provide a greater net benefit for clinical decision making. PATIENT SUMMARY: Prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA and the Prostate Health Index, are associated with adverse characteristics of prostate cancer; however, these biomarkers provided only a slight net benefit for clinical decision making. PMID- 25139199 TI - Reply from authors re: David Margel. Metformin to prevent prostate cancer: a call to unite. Eur urol 2014;66:1021-2. PMID- 25139201 TI - Mechanisms of remembering the past and imagining the future--new data from autobiographical memory tasks in a lifespan approach. AB - We investigated the episodic/semantic distinction in remembering the past and imagining the future and explored cognitive mechanisms predicting events' specificity throughout the lifespan. Eighty-three 6- to 81-year-old participants, divided into 5 age groups, underwent past, present and future episodic (events' evocation) and semantic (self-descriptions) autobiographical tasks and a complementary cognitive test battery (executive functions, working and episodic memory). The main results showed age effects on episodic events' evocation indicating an inverted U function (i.e., developmental progression from 6 to 21years and aging decline). By contrast, age effects were slighter on self descriptions while self-defining events' evocation increased with age. Furthermore, age effects on episodic events' evocation were mainly mediated by age effects on cognitive functions and personal semantics. These new findings indicate a developmental and aging episodic/semantic distinction for both remembering the past and imagining the future, and suggest that above similarities, these abilities could have a fundamentally different basis. PMID- 25139200 TI - Radiologically determined orthodontically induced external apical root resorption in incisors after non-surgical orthodontic treatment of class II division 1 malocclusion: a systematic review. AB - This study aims to critically evaluate orthodontically induced external apical root resorption (OIEARR) in incisors of patients undergoing non-surgical orthodontic treatment of class II division 1 malocclusion by a systematic review of the published data. An electronic search of two databases was performed; the bibliographies of relevant articles were also reviewed. Studies were included if they examined the amount of OIEARR in incisors produced during non-surgical orthodontic treatment of individuals with class II division I malocclusion in the permanent dentition. Individuals had no previous history of OIEARR, syndromes, pathologies, or general diseases. Study selections, risk of bias assessment, and data extraction were performed in duplicate. Eight studies of moderate methodological quality were finally included. An increased prevalence (65.6% to 98.1%) and mild to moderate severity of OIEARR (<4 mm and <1/3 original root) were reported. No sex difference in root resorption was found. For the maxillary incisors, there was no evidence that either the central or lateral incisor was more susceptible to OIEARR. A weak to moderate positive correlation between treatment duration and root resorption, and anteroposterior apical displacement and root resorption was found. Current limited evidence suggests that non surgical comprehensive orthodontic treatment to correct class II division 1 malocclusions causes increased prevalence and severity of OIEARR the more the incisor roots are displaced and the longer this movement takes. PMID- 25139203 TI - Antiretroviral therapy initiation in an Australian cohort: implications for increased use of antiretroviral therapy. AB - Human immunodeficiency virus (HIV) management is entering a "universal test and treat" phase, although the benefits from this approach in developed world scenarios are uncertain. We analyzed 79 combination anti-retroviral therapy (cART)-naive HIV-positive individuals who were intensively prospectively followed from 2004 to 2013. We studied HIV-related illnesses, potential HIV transmissions, impact on sexual behavior, and factors impeding earlier cART initiation. Sixty eight (86 %) subjects commenced cART at a mean of 6.0 years after diagnosis: 71 % with a CD4 T-cell count <350 cells/MUl. A significant minority of subjects (29 %) resisted initiation of cART despite physician recommendation for a mean of 18 months. Only one HIV-related illness occurred in a patient who had not previously recorded a CD4 T-cell count <500 cell/MUl, totaling 195 person-years of observation. A 40 % increase in sexually transmitted infections (STIs) occurred after commencing cART. We detected six HIV transmissions in our cohort, all of which were before initiating cART and 5 of them had a prior CD4 T-cell count <500 cells/MUl. Illnesses related to cART deferral were rare and most HIV transmissions we detected occurred in people with a prior CD4 T-cell count <500 cells/MUl. Our study raises concerns about increasing STI rates after cART initiation. Focusing resources on cART initiation among patients with CD4 T-cell counts <500 cells/MUl and enhancing safe sexual practices should remain a priority. PMID- 25139202 TI - Multicenter phase II study of a combination of cyclosporine a, methotrexate and mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG). AB - BACKGROUND: Improvement of current GVHD prophylactic therapies remains an important goal in the allo-HSCT. We have described a novel prophylaxis regimen in a single institution trial. The Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) initiated a phase II multicenter study. METHODS: The study was designed as a prospective, single arm phase II open-label, multicenter clinical trial. The primary endpoint was improvement of aGVHD by 25% over historical control (40%) in Chinese patients. 508 patients were enrolled. All of the patients received cyclosporine A (CsA), methotrexate (MTX) and mycophenolate mofetil (MMF) (0.5-1.0 g daily for 30 days) as GVHD prophylaxis regimen. RESULTS: The primary endpoint was met with cumulative incidences of grades 2 to 4 and grades 3 to 4 aGVHD of 23.2% and 10.3%, respectively. Incidence for cGVHD was 67.4%. The non-relapse mortality (NRM) rate was 18.4% at 2 years. The probabilities of leukemia free survival (LFS) for non-advanced stage and advanced stage patients at 2 years were 69.7% and 44.8% respectively (p = 0.000). Recipient age >= 40 years, advanced stage and Busulfan-Fludarabine(BuFlu) conditioning regimen were identified as major risk factors for aGVHD. Recipient age >= 40 years, BuFlu conditioning regimens, female donor/male recipient and prior aGVHD were associated with cGVHD. Despite lower RM (relapse mortality), patients with grade 2-4 aGVHD had higher NRM and worse OS and LFS compared to patients with grade 0-1 aGVHD. In contrast, patients with cGVHD had better OS and LFS and lower RM compared to patients without cGVHD. CONCLUSION: The novel GVHD regimen decreased the risk for aGVHD by 42% without improving the risk for cGVHD compared to historical controls. Development of aGVHD was associated with worse OS and LFS as well as higher NRM. In contrast, cGVHD was associated with improved OS and LFS likely attributed to a GVL effect. PMID- 25139204 TI - A common copy number variation polymorphism in the CNTNAP2 gene: sexual dimorphism in association with healthy aging and disease. AB - BACKGROUND: New therapeutic targets are needed to fight aging-related diseases and increase life span. A new female-specific association with diseases and limited survival past 80 years was recently reported for a copy number variation (CNV) in the CNTNAP4 gene from the neurexin superfamily. OBJECTIVE: We asked whether there are CNVs that are associated with aging phenotypes within other genes from the neurexin superfamily and whether this association is sex specific. METHODS: Select CNV polymorphisms were genotyped with proprietary TaqMan qPCR assays. RESULTS: A case/control study, in which a group of 81- to 90-year-old community-dwelling Caucasians with no chronic diseases (case) was compared to a similar control group of 65- to 75-year-olds, revealed a negative association with healthy aging for the ins allele of common esv11910 CNV in the CNTNAP2 gene (n = 388; OR = 0.29, 95% CI: 0.14-0.59, p = 0.0004 for males, and OR = 0.82, 95% CI: 0.42-1.57, p = 0.625 for females). This male-specific association was validated in a study of an independent group of 76- to 80-year-olds. To look for a corresponding positive association of the allele with aging-related diseases, two case subgroups of 81- to 90-year-olds, one composed of individuals with cognitive impairment and the other with various diseases not directly related to the nervous system, such as cardiovascular diseases, etc., were compared to a healthy control subgroup of the same age. A positive male-specific association was found for both cases (OR = 2.75, p = 0.008 for association with cognitive impairment, and OR = 3.18, p = 0.002 for other diseases combined). CONCLUSIONS: A new male-specific association with aging is reported for a CNV in the CNTNAP2 gene. The polymorphism might be useful for diagnosing individual genetic predispositions to healthy aging versus aging complicated by chronic diseases. PMID- 25139205 TI - Drug prescription by telephone consultation in Danish out-of-hours primary care: a population-based study of frequency and associations with clinical severity and diagnosis. AB - BACKGROUND: Danish general practitioners (GPs) answer all calls to the out-of hours primary care service. About 60% of the calls are terminated on the telephone through provision of medical advice and prescription of medication. Nevertheless, little is known about the prescription patterns of telephone consultations, such as prescription frequency and indications for drug use. Our aim was to examine the characteristics of patients and GPs in telephone consultations resulting in drug prescription. METHODS: The study was based on a 12-month survey on reasons for encounter in the Danish out-of-hours primary care service. A total of 385 GPs (55.5% of all GPs from Central Denmark Region on duty during a year) participated in answering electronic pop-up questionnaires integrated in the electronic patient administration system. The questionnaires contained items on reasons for encounter (e.g. existing chronic disease or new health problem), diagnoses, and GP-assessed severity of the health problem. Data on time of contact, patient gender and age, and prescribed medication (Anatomic Therapeutic Chemical classifications) for telephone consultations were obtained from the patient administration system. Differences in characteristics of patients, general practitioners, and contacts were examined, and associations with prescribed medication were analysed using a multivariate analysis with prevalence ratios. RESULTS: Medication was prescribed in 19.9% of the included 4,173 telephone consultations; antibiotics and analgesics were prescribed most frequently (10.8% and 2.5%, respectively). GPs tended to assess contacts resulting in antibiotic prescription as more severe than other contacts. For high severity contacts, there was a lower likelihood for prescription (prevalence ratio = 0.28 (0.16-0.47)). Children aged 0-4 years had lower probability of receiving a prescription compared with patients aged 18-40 years. The prescription rate was highest during the first four hours of the opening hours of the out-of-hours primary care service. CONCLUSION: One in five of all telephone consultations involved drug prescription; antibiotics constituted half of these prescriptions. Drug prescription by telephone was less likely to be offered in cases involving 'severe' reason for encounter or children. This study calls for further studies of drug prescriptions issued via out-of-hours primary care telephone consultations. PMID- 25139206 TI - Prenatal exposure to perfluoroalkyl substances and the risk of congenital cerebral palsy in children. AB - Perfluoroalkyl substances (PFASs) are persistent pollutants and endocrine disruptors that may affect fetal brain development. We investigated whether prenatal exposure to PFASs increases the risk of congenital cerebral palsy (CP). The source population for this study includes 83,389 liveborn singletons and mothers enrolled in the Danish National Birth Cohort during 1996-2002. We identified 156 CP cases by linking the cohort to the Danish National Cerebral Palsy Register, and we randomly selected 550 controls using a case-cohort design. We measured 16 PFASs in maternal plasma collected in early or midpregnancy, and 6 PFASs were quantifiable in more than 90% of the samples. We found a higher risk of CP in boys with higher maternal PFAS levels; per 1-unit (natural-log ng/mL) increase, the risk ratios were 1.7 (95% confidence interval: 1.0, 2.8) for perfluorooctane sulfonate and 2.1 (95% confidence interval: 1.2, 3.6) for perfluorooctanoic acid. We also observed a dose-response pattern of CP risk in boys per quartile of maternal level of perfluorooctane sulfonate and perfluorooctanoic acid (P for trend < 0.01). PFASs were associated with both unilateral and bilateral spastic CP subphenotypes. No association between PFASs and CP was found in girls. Prenatal exposures to PFASs may increase the risk of CP in boys, but the finding is novel and replication is needed. PMID- 25139207 TI - Ozone and daily mortality rate in 21 cities of East Asia: how does season modify the association? AB - Previous studies in East Asia have revealed that the short-term associations between tropospheric ozone and daily mortality rate were strongest in winter, which is opposite to the findings in North America and Western Europe. Therefore, we investigated the season-varying association between ozone and daily mortality rate in 21 cities of East Asia from 1979 to 2010. Time-series Poisson regression models were used to analyze the association between ozone and daily nonaccidental mortality rate in each city, testing for different temperature lags. The best fitting model was obtained after adjustment for temperature in the previous 2 weeks. Bayesian hierarchical models were applied to pool the city-specific estimates. An interquartile-range increase of the moving average concentrations of same-day and previous-day ozone was associated with an increase of 1.44% (95% posterior interval (PI): 1.08%, 1.80%) in daily total mortality rate after adjustment for temperature in the previous 2 weeks. The corresponding increases were 0.62% (95% PI: 0.08%, 1.16%) in winter, 1.46% (95% PI: 0.89%, 2.03%) in spring, 1.60% (95% PI: 1.03%, 2.17%) in summer, and 1.12% (95% PI: 0.73%, 1.51%) in fall. We found significant associations between short-term exposure to ozone and higher mortality rate in East Asia that varied considerably from season to season with a significant trough in winter. PMID- 25139209 TI - Smoking decreases structural and functional resilience in the subgingival ecosystem. AB - AIMS: Dysbiotic microbial communities underlie the aetiology of several oral diseases, especially in smokers. The ability of an ecosystem to rebound from the dysbiotic state and re-establish a health-compatible community, a characteristic known as resilience, plays an important role in susceptibility to future disease. The present investigation was undertaken to examine the effects of smoking on colonization dynamics and resilience in marginal and subgingival biofilms. MATERIALS AND METHODS: Marginal and subgingival plaque and gingival crevicular fluid samples were collected from 25 current and 25 never smokers with pre existing gingivitis at baseline, following resolution, after 1, 2 4, 7, 14 and 21 days of undisturbed plaque formation and following resolution. 16S cloning and sequencing was used for bacterial identification and multiplexed bead-based flow cytometry was used to quantify the levels of 27 immune mediators. RESULTS: Smokers demonstrated an early pathogenic colonization that led to sustained pathogen enrichment with periodontal and respiratory pathogens, eliciting a florid immune response. Smokers also demonstrated greater abundance of pathogenic species, poor compositional correlation between marginal and subgingival ecosystems, and significantly greater pro-inflammatory responses following resolution of the second episode of disease. CONCLUSIONS: The ability of the subgingival microbiome to "reset" itself following episodes of disease is decreased in smokers, thereby lowering the resilience of the ecosystem and decreasing its resistance to future disease. PMID- 25139210 TI - Single-incision laparoscopic cholecystectomy for cholecystitis requiring percutaneous transhepatic gallbladder drainage. AB - PURPOSE: Single-incision laparoscopic cholecystectomy (SILC) has been performed for patients with gallbladder stones but without acute cholecystitis. We report our experience of performing SILC for patients with cholecystitis requiring percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: We performed SILC via an SILS-Port with additional 5-mm forceps through an umbilical incision in ten patients with cholecystitis requiring PTGBD. RESULTS: All procedures were completed successfully. The mean operative time was 124 min (range 78-169 min) and there were no intraoperative or postoperative complications. The mean postoperative hospital stay was 2.7 days. All patients were satisfied with the cosmetic results. CONCLUSIONS: Our procedure may represent an alternative to conventional laparoscopic cholecystectomy (CLC) for patients who fervently demand the cosmetic advantages, despite cholecystitis requiring PTGBD. SILC should be performed carefully to avoid bile duct injury because the only advantage of SILC over CLC is cosmetic. PMID- 25139211 TI - Current status of third-generation implantable left ventricular assist devices in Japan, Duraheart and HeartWare. AB - Recently, left ventricular assist devices (LVADs) have become a viable therapeutic approach as a bridge to cardiac transplantation, as well as destination therapy or as part of the bridge to recovery. In Japan, paracorporeal pneumatic devices are the only choice for such therapy, as implantable LVADs are not yet generally available due to device lag, which represents a serious problem in this field. Clinical trials of four different continuous-flow pumps, both axial and centrifugal flow types, were completed at about the same time, and two of those devices, DuraHeart and EVAHEART, have already been approved for use in Japan. Thus, reports of advanced treatment for severe heart failure with these devices are expected. The DuraHeart (Terumo Heart, Ann Arbor, MI, USA) and another device named the HeartWare (HeartWare Inc, Miami Lakes, FL, USA) are so called third-generation devices, as they have achieved miniaturization and improvements in performance from the use of magnetic levitation. Based on our experiences from both clinical research and experimental use, we herein discuss the DuraHeart and HeartWare devices, with a focus on the clinical outcomes and management strategies. Because of the long waiting period for heart transplantation in Japan, these two devices are considered to have important roles in the near future for the treatment of severe heart failure, and a comprehensive strategy for LVAD therapy including such third-generation implantable devices is expected. PMID- 25139208 TI - Effect of different human papillomavirus serological and DNA criteria on vaccine efficacy estimates. AB - Two trials of clinically approved human papillomavirus (HPV) vaccines, Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE I/II) and the Papilloma Trial Against Cancer in Young Adults (PATRICIA), reported a 22% difference in vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 2 or worse in HPV-naive subcohorts; however, serological testing methods and the HPV DNA criteria used to define HPV-unexposed women differed between the studies. We applied previously described methods to simulate these HPV-naive subcohorts within the Costa Rica HPV16/18 Vaccine Trial and assessed how these criteria affect the estimation of VE. We applied 2 enzyme-linked immunosorbent assay (ELISA) thresholds for HPV16 and HPV18 seropositivity (8 and 7 ELISA units/mL, respectively, for PATRICIA; 54 and 65 ELISA units/mL, respectively, for FUTURE I/II (to approximate the competitive Luminex immunoassay)) and 2 criteria for HPV DNA positivity (12 oncogenic HPV types, plus HPV66 and 68/73 for PATRICIA; or plus HPV6 and 11 for FUTURE I/II). VE was computed in the 2 naive subcohorts. Using the FUTURE I/II and PATRICIA criteria, VE estimates against cervical intraepithelial neoplasia grade 2 or worse, regardless of HPV type, were 69.0% (95% confidence interval: 40.3%, 84.9%) and 80.8% (95% confidence interval: 52.6%, 93.5%), respectively (P = 0.1). Although the application of FUTURE I/II criteria to our cohort resulted in the inclusion of more sexually experienced women, methodological differences did not fully explain the VE differences. PMID- 25139212 TI - Appearance deceives: unusual pneumothorax: traumatic phrenic nerve paralysis. PMID- 25139213 TI - Cardiac involvement in chronic progressive external ophthalmoplegia. AB - Myocardial involvement has not been extensively investigated in mitochondrial myopathies. The aim of the study was to assess the myocardial morpho-functional changes in patients with chronic progressive external ophthalmoplegia (PEO). Twenty patients with PEO and 20 controls underwent standard echocardiography with tissue Doppler imaging (TDI) and integrated backscatter (IBS) analyses. These techniques are capable of providing non-invasively the early, subtle structural and functional changes of the myocardium. TDI myocardial systolic (Sm) and early (Em) and late (Am) diastolic velocities of left ventricular walls were determined. The systo-diastolic variation of IBS was also determined. Patients with PEO exhibited lower Sm, lower Em, and higher Am, and a reduced Em/Am ratio than controls (p<0.001 for all) at interventricular septum and lateral wall levels. In PEO patients, septal and posterior wall cyclic variations of IBS were significantly lower than those in controls (p<0.001). Patients with PEO showed myocardial wall remodeling characterized by increased fibrosis and early left ventricular systo-diastolic function abnormalities. Although cardiac involvement in PEO is generally considered to be limited to the cardiac conduction system, left ventricular dysfunction may be present and should receive more attention in the management of these patients. PMID- 25139214 TI - Admission of hematopoietic cell transplantation patients to the intensive care unit at the Pontificia Universidad Catolica de Chile Hospital. AB - Patients undergoing hematopoietic cell transplantation (HCT) can have complications that require management in the intensive care unit (ICU). We conducted a retrospective study of patients undergoing HCT between 2007 and 2011 with admission to the ICU. We analyzed 97 patients, with an average age of 37 (range, 15 to 68). The main indications for HCT were hematologic malignancies (84%, n = 82). Ninety percent (n = 87) received myeloablative conditioning. Thirty-one percent were admitted (autologous transplant recipients 15%, allogeneic transplant recipients 34%, and umbilical cord blood [UCB] transplant recipients 48%) with an average length of stay of 19 days (range, 1 to 73 days). The average time between transplantation and transfer was 15 days. The main causes of admission were acute respiratory failure (63%) and septic shock (20%). ICU mortality was 20% for autologous transplantations and 64% for allogeneic transplantations (adult donor and UCB combined). On average, patients died 108 days after the transplantation (range, 4 to 320 days). One-year overall survival, comparing patients entering the ICU with those never admitted, was 16% versus 82% (P < .0001) for allogeneic transplantations (adult donor and UCB combined) and 80% versus 89% (P = not significant) for autologous transplantations. Acute graft versus-host disease was significantly associated with death in ICU after UCB HCT. ICU support is satisfactory in about one half of patients admitted, characterized by a short and medium term prognosis not as unfavorable as has been previously reported. PMID- 25139215 TI - The outcome of allogeneic hematopoietic cell transplantation for children with FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous leukemia. AB - FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is a somatic mutation associated with poor outcome when treated with chemotherapy alone. In children, hematopoietic stem cell transplantation (HSCT) is recommended, but very limited data on outcome are reported. We determined the outcome of 29 children with FLT3/ITD-positive acute myelogenous leukemia (AML) who underwent allogeneic HSCT in 4 pediatric centers. Eleven patients (38%) received matched related donor hematopoietic stem cells and 18 (62%) received alternative donors. Eighteen patients (62%) received total body irradiation (TBI)-based regimens. No patients experienced transplantation-related mortality. Eleven patients (38%) experienced relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% (95% confidence interval [CI], 20.4% to 54.9%). Two-year disease-free survival (DFS) and overall survival (OS) were 65.3% (95% CI, 45.1% to 79.6%) and 82.2% (95% CI, 58.5% to 91.3%), respectively. There was no difference in the DFS of patients who received transplants from related donors versus the DFS of those who received transplants from alternative donors (hazard ratio [HR], 2.64; 95% CI, .79 to 8.76; P = .10), using univariate analysis. Patients with higher FLT3/ITD ratio at diagnosis had significantly worse DFS (HR, 1.42; 95% CI, 1.04 to 1.93; P = .03). The use of TBI in the preparative regimen was associated with superior DFS (HR, .29; 95% CI, .08 to .99; P = .04) and OS (HR, .07; 95% CI, .01 to .62; P = .002). We conclude that allogeneic HSCT improves DFS and OS in children with FLT3/ITD positive AML compared with what has been reported in those treated with chemotherapy alone. PMID- 25139217 TI - Cytomegalovirus infection in patients who underwent allogeneic hematopoietic stem cell transplantation in Portugal: a five-year retrospective review. AB - Cytomegalovirus (CMV) infection is 1 of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (aHSCT), mainly within the first 100 days after transplantation. We aimed to characterize CMV infection in a cohort of 305 patients with different malignancies undergoing aHSCT at the Portuguese Institute of Oncology of Porto between January 2008 and December 2012. In total, 184 patients (60.3%) developed CMV infection, mainly viral reactivations rather than primary infections (96.2% versus 3.8%, respectively). The majority of patients (166 of 184) developed CMV infection <=100 days after transplantation, with median time to infection of 29 days (range, 0 to 1285) and median duration of infection of 10 days (range, 2 to 372). Multivariate analysis revealed that CMV infection was increased in donor (D) /recipient (R)+ and D+/R+ (odds ratio [OR], 10.5; 95% confidence interval [CI], 4.35 to 25.4; P < .001) and in patients with mismatched or unrelated donors (OR, 2.54; 95% CI, 1.34 to 4.80; P = .004). Cox regression model showed that the risk of death was significantly increased in patients >38 years old (OR, 1.89; 95% CI, 1.14 to 3.12; P = .0137), who underwent transplantation with peripheral blood (OR, 3.02; 95% CI, 1.33 to 6.86; P = .008), with mismatched or unrelated donor (OR, 2.16; 95% CI, 1.48 to 3.13; P < .001), and who developed CMV infection (OR, 1.76; 95% CI, 1.07 to 2.90; P = .025). Moreover, patients who developed CMV infection had a significantly reduced median post-transplantation survival (16 versus 36 months; P = .002). PMID- 25139218 TI - Maternal serum PAPP-A as an early marker of obstetric complications? AB - OBJECTIVE: The aim of this study was to investigate whether low first-trimester PAPP-A levels are associated with an adverse pregnancy outcome. MATERIALS AND METHODS: A retrospective case-control study was carried out using a Down's syndrome assays database over a 6-year period, between the 8th and 11th week of pregnancy. There were 164 women with PAPP-A multiples of median (MoM) levels <0.3 and 1,640 women with PAPP-A MoM levels >=0.3 who served as a control group. Outcome measures were the prevalence of miscarriages, gestational hypertension, preeclampsia, pre-term delivery, gestational diabetes and intrauterine growth retardation in both groups. RESULTS: The two groups significantly differed only for miscarriages: 29 (17.7%) vs. 159 (9.7%), p = 0.04, OR 1.7; gestational hypertension: 15 (9.1%) vs. 74 (4.5%), p = 0.02, OR 2.1, and preeclampsia: 9 (5.5%) vs. 29 (1.8%), p = 0.02, OR 2.5. DISCUSSION: Even if in this study the PAPP-A cutoff considered was lower and was assayed in an earlier period compared with other studies, the detection rate for adverse pregnancy outcomes did not improve. PMID- 25139216 TI - Safety and efficacy of targeted-dose busulfan and bortezomib as a conditioning regimen for patients with relapsed multiple myeloma undergoing a second autologous blood progenitor cell transplantation. AB - Patients with multiple myeloma (MM) who relapse after autologous transplantation have limited therapeutic options. We conducted a prospective, multicenter, phase IIa study to investigate the safety and efficacy of i.v. busulfan (Bu) in combination with bortezomib as a conditioning regimen for a second autotransplantation. Because a safe Bu exposure was unknown in patients receiving this combination, Bu was initially targeted to a total area under the concentration-time curve (AUC) of 20,000 MUM * minute. As no concentration limiting toxicity was observed in 6 patients, this Bu exposure was utilized in the following treatment cohort (n = 24). Individualized Bu dose, based on test dose .8 mg/kg pharmacokinetics (PK), was administered daily for 4 consecutive days starting 5 days before transplantation, followed by a single dose of bortezomib (1.3 mg/m(2)) 1 day before transplantation. The total mean dose of i.v. Bu (including the test dose and 4-day administration) was 14.2 mg/kg (standard deviation = 2.48; range, 8.7 to 19.2). Confirmatory PK demonstrated that only 2 of 30 patients who underwent transplantation were dosed outside the Bu AUC target and dose adjustments were made for the last 2 doses of i.v. Bu. The median age was 59 years (range, 48 to 73). Median time from first to second transplantation was 28.0 months (range, 12 to 119). Of 26 evaluable patients, 10 patients attained a partial response (PR) or better at 3 months after transplantation, with 2 patients attaining a complete response. At 6 months after transplantation, 5 of 12 evaluable patients had maintained or improved their disease status. Median progression-free survival was 191 days, whereas median overall survival was not reached during the study period. The most common grade 3 and 4 toxicities were febrile neutropenia (50.0%) and stomatitis (43.3%). One transplantation-related death was observed. A combination of dose-targeted i.v. Bu and bortezomib induced PR or better in one third of patients with MM who underwent a second autotransplantation, with acceptable toxicity. PMID- 25139219 TI - Anti-amyloidogenic property of human gastrokine 1. AB - Gastrokine 1 (GKN1) is a stomach-specific protein expressed in normal gastric tissue but absent in gastric cancer. GKN1 plays a major role in maintaining gastric mucosa integrity and is characterized by the presence of a BRICHOS domain consisting of about 100 amino acids also found in several unrelated proteins associated with major human diseases like BRI2, related to familial British and Danish dementia and surfactant protein C (SP-C), associated with respiratory distress syndrome. It was reported that recombinant BRICHOS domains from BRI2 and SP-C precursor (proSP-C) prevent fibrils formation of amyloid-beta peptide (Abeta), that is the major component of extracellular amyloid deposits in Alzheimer's disease. Here we investigated on the interaction between human recombinant GKN1 (rGKN1) and Abeta peptide (1-40) that derives from the partial hydrolysis of the amyloid precursor protein (APP). GKN1 prevented amyloid aggregation and fibrils formation by inhibiting Abeta(1-40) polymerization, as evaluated by SDS-PAGE, thioflavin-T binding assay and gel filtration experiments. Mass spectrometry showed the formation of a prevailing 1:1 complex between GKN1 and Abeta(1-40). SPR analysis of GKN1/Abeta interaction led to calculate a dissociation constant (KD) of 34 MUM. Besides its interaction with Abeta(1-40), GKN1 showed also to interact with APP as evaluated by confocal microscopy and Ni NTA pull-down. Data strongly suggest that GKN1 has anti-amyloidogenic properties thus functioning as a chaperone directed against unfolded segments and with the ability to recognize amyloidogenic polypeptides and prevent their aggregation. PMID- 25139220 TI - Bacterial role in pine wilt disease development - review and future perspectives. AB - Mutualistic and beneficial relationships between nematodes and bacteria are highly present in nature, mostly occurring because of nutritional dependence and pathogen protection, and intrinsically related with the environment, the ecological conditions and the nematode life stages. Thirty-four years have passed since the first hypothesis suggesting a bacterial role in pine wilt disease (PWD), associated with the pinewood nematode (PWN), Bursaphelenchus xylophilus. In 1980, researchers reported that bacteria associated with the PWN could produce toxins that lead to PWD development in pine seedlings. It was also suggested a double vector system for PWD, where bacteria were vectored by the PWN and the PWN vectored by an insect from the Monochamus genus. Presently, the specific involvement of bacteria in such complex disease is still controversial, even though the increased number of studies focused on the potential bacteria role has increased considerably. This review is an up-to-date comprehensive perspective and brings new insights on the role of PWN-associated bacteria in PWD. PMID- 25139221 TI - Residues of deoxynivalenol (DON) and its metabolite de-epoxy-DON in eggs, plasma and bile of laying hens of different genetic backgrounds. AB - In the present study, the potential for carry-over of deoxynivalenol (DON) into eggs and DON residues in plasma and bile of laying hens of different genetic backgrounds after long-term feeding trial was investigated. A total of 80, 23 week-old laying hens were assigned to a feeding trial with two diets, a control diet and a Fusarium toxin-contaminated diet (FUS) (0.4 and 9.9 mg DON kg(-1), respectively). In the 60th week of hen's life, 10 eggs from each group were collected. In the 70th week of hen's life, all hens were slaughtered and samples of blood and bile were collected. The samples were analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for DON and de-epoxy-DON. DON was only detected in samples of hens which fed the FUS diet while none of the samples analysed had detectable levels of de-epoxy-DON. In plasma and bile samples, DON levels ranged from 0.2 to 0.6 ng ml(-1) and from 1.8 to 4.1 ng ml( 1), respectively. DON levels in egg yolk and albumen ranged between 0.0-0.46 ng g(-1) and 0.0-0.35 ng g(-1), respectively, corresponding to carry-over rates of DON into eggs from 0.0 to 0.000016. Moreover, no differences in DON levels or carry-over rates were noticed between the two tested breeds. These results show that very low levels of DON were transferred into eggs and indicate that although eggs could contribute to human exposure to DON, the levels are very low and insignificant. PMID- 25139222 TI - Effects of the volatile anesthetic sevoflurane on tonic GABA currents in the mouse striatum during postnatal development. AB - The volatile anesthetic sevoflurane, which is widely used in pediatric surgery, has proposed effects on GABAA receptor-mediated extrasynaptic tonic inhibition. In the developing striatum, medium-sized spiny projection neurons have tonic GABA currents, which function in the excitatory/inhibitory balance and maturation of striatal neural circuits. In this study, we examined the effects of sevoflurane on the tonic GABA currents of medium spiny neurons in developing striatal slices. Sevoflurane strongly increased GABAA receptor-mediated tonic conductance at postnatal days 3-35. The antagonist of the GABA transporter-1, 1-[2 [[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride further increased tonic GABA conductance during the application of sevoflurane, thereby increasing the total magnitude of tonic currents. Both GABA (5 MUM) and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol hydrochloride, the delta-subunit-containing GABAA receptor agonist, induced tonic GABA currents in medium spiny neurons but not in cholinergic neurons. However, sevoflurane additively potentiated the tonic GABA currents in both cells. Interestingly, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol hydrochloride sensitive neurons made a large current response to sevoflurane, indicating the contribution of the delta-subunit on sevoflurane-enhanced tonic GABA currents. Our findings suggest that sevoflurane can affect the tone of tonic GABA inhibition in a developing striatal neural network. PMID- 25139223 TI - A safety evaluation of aripiprazole for treating schizophrenia during pregnancy and puerperium. AB - INTRODUCTION: Aripiprazole (ARI) is a second-generation antipsychotic acting as a dopamine-serotonin system stabilizer and partial agonist at D2 receptors. The drug is indicated in several and severe psychiatric disorders which are particularly frequent in women during the childbearing age. AREA COVERED: A systematic review of studies investigating the reproductive safety of ARI. EXPERT OPINION: For first trimester use, reviewed data provide no clear evidence about the safety of the drug for the developing fetus. However, a decline of plasma levels (PLs) throughout the pregnancy compared with PLs before pregnancy was observed. This finding suggests the need to increase the dosage during pregnancy in order to maintain stable PLs. If used during late pregnancy, some signals exist suggesting that ARI may worse neonatal outcomes. Hence, clinicians should consider withdrawing the drug before the last month of pregnancy to reduce the risks of neonatal complications. However, such risks must be weighed against the risks of woman's symptom deterioration. In any case, parturition should happen in hospitals equipped with well-organized neonatal intensive care units. No information is available on the impact of antenatal exposure to ARI on the main neurodevelopmental milestones. Infant exposure to the drug through maternal milk may increase the risk of insufficient milk production and neonatal somnolence. PMID- 25139224 TI - Diagnostic laparoscopy with 5-aminolevulinic-acid-mediated photodynamic diagnosis enhances the detection of peritoneal micrometastases in advanced gastric cancer. AB - OBJECTS: Recently, we reported that diagnostic laparoscopy with photodynamic diagnosis using oral 5-aminolevulinic acid (ALA-PDD) is a promising tool for diagnosing early peritoneal metastases in gastric cancer. The present study evaluated the usefulness of adding ALA-PDD to conventional diagnostic laparoscopy and assessed the association of the ALA-PDD results with peritoneal fluid cytology and molecular diagnostic testing. METHODS: Diagnostic laparoscopy using sequential white light (WL) and ALA-PDD observations was performed in 52 advanced gastric cancer patients, and the sensitivity of ALA-PDD for detecting peritoneal disease was compared to WL. Peritoneal fluid samples from the same patients were also subjected to cytological examination and molecular diagnosis using a transcription-reverse transcription concerted reaction (TRC). RESULTS: Twenty four of the 52 patients (46%) had no macroscopic evidence of peritoneal metastases on WL examination; however, ALA-PDD detected dissemination in 5 of these 24 patients (21%) (pd-P). Cytological examination was negative in 4 of the 5 pd-P patients, and molecular testing using TRC was negative in 3 of the 5 pd-P patients. CONCLUSIONS: This study demonstrated that diagnostic laparoscopy with ALA-PDD improved the sensitivity for the detection of peritoneal metastases. ALA PDD may be a useful technique for the preoperative staging of advanced gastric cancer and can complement examinations of peritoneal lavage fluids. PMID- 25139225 TI - Blue-colored tert-butylamine clathrate hydrate. AB - Clathrate hydrates preserve active species more stably than the other icy materials and investigation of the behavior of the active species elucidates the physicochemical properties of clathrate hydrates like guest-guest interaction. Color of the tert-butylamine clathrate hydrate changes to blue after gamma irradiation and is bleachable with visible light. The electron spin resonance (ESR) spectrum at 120 K mainly consists of a triplet signal of the C-centered radical NH2C(CH3)2CH2* together with a single signal at g = 2.0008. The latter signal disappears after light exposure. These results indicate that both the blue color and the single ESR signal are derived from trapped electrons in the hydrate. They thermally decay around 140-160 K by the first-order reaction, and the activation energy is 27 kJ/mol. Since tert-butylamine molecules can capture protons due to the high proton affinity, electrons may remain in the hydrate without reacting with protons, making the hydrate blue after gamma irradiation. The long-lived trapped electrons in the tert-butylamine hydrate have an advantage to investigate those in icy materials because tert-butylamine hydrate is nonionic and has a tetra-coordinated host water network like crystalline ice without any substitution for water molecules. PMID- 25139226 TI - Periodontal dressing after surgical crown lengthening: a randomized clinical trial. AB - OBJECTIVE: The aim of the present study was to evaluate the effect of periodontal dressing on post-operative pain and swelling after surgical crown lengthening. MATERIALS AND METHODS: A blind, randomized, clinical trial was carried out with 36 patients. Following surgical crown lengthening, the individuals were randomly allocated to the periodontal dressing group (PDG) and control group (CG, non placement of periodontal dressing). Pain and discomfort were analyzed using a visual analog scale (VAS), verbal scale (VS) and the number of analgesics consumed in 7 days post-operatively. Post-operative infection, stability of the gingival margin and type of healing were also evaluated. RESULTS: The PDG had a significantly higher percentage of responses of 'strong pain' on the VS in the first day post-operatively (33.3% vs 5.3%, p = 0.03) and greater pain on the first and second days post-operatively based on the VAS. Moreover, a significant difference between groups was found regarding gingival swelling after 7 days. However, gingival recession was found in 57.8% of the sites in the CG and only 5.5% of sites in the PDG. No change in condition was found among individuals with conjunctive tissue/bone exposure in the CG in the immediate post-operative period and 80% of the patients in the PDG had healing by first intention after 7 days. CONCLUSION: The use of periodontal dressing seems to be preferable following surgical crown lengthening with connective tissue/bone exposure. However, adequate post-operative analgesic strategies should be employed due to the possibility of intense pain in the first 24 hours. PMID- 25139227 TI - The therapeutic potential of a C-X-C chemokine receptor type 4 (CXCR-4) antagonist on hypertrophic scarring in vivo. AB - Effective prevention and treatment of hypertrophic scars (HTSs), a dermal form of fibrosis that frequently occurs following thermal injury to deep dermis, are unsolved significant clinical problems. Previously, we have found that stromal cell-derived factor 1/CXCR4 signaling is up-regulated during wound healing in burn patients and HTS tissue after thermal injury. We hypothesize that blood borne mononuclear cells are recruited into wound sites after burn injury through the chemokine pathway of stromal cell-derived factor 1 and its receptor CXCR4. Deep dermal injuries to the skin are often accompanied by prolonged inflammation, which leads to chemotaxis of mononuclear cells into the wounds by chemokine signaling where fibroblast activation occurs and ultimately HTS are formed. Blocking mononuclear cell recruitment and fibroblast activation, CXCR4 antagonism is expected to reduce or minimize scar formation. In this study, the inhibitory effect of CXCR4 antagonist CTCE-9908 on dermal fibrosis was determined in vivo using a human HTS-like nude mouse model, in which split-thickness human skin is transplanted into full-thickness dorsal excisional wounds in athymic mice, where these wounds subsequently develop fibrotic scars that resemble human HTS as previously described. CTCE-9908 significantly attenuated scar formation and contraction, reduced the accumulation of macrophages and myofibroblasts, enhanced the remodeling of collagen fibers, and down-regulated the gene and protein expression of fibrotic growth factors in the human skin tissues. These findings support the potential therapeutic value of CXCR4 antagonist in dermal fibrosis and possibly other fibroproliferative disorders. PMID- 25139228 TI - Investigation of age-related differences in an adapted Hayling task. AB - The Hayling task is traditionally used to assess activation and inhibitory processes efficiency among various populations, such as elderly adults. However, the classical design of the task may also involve the influence of strategy use and efficiency of sentence processing in the possible differences between individuals. Therefore, the present study investigated activation and inhibitory processes in aging with two formats of an adapted Hayling task designed to reduce the involvement of these alternative factors. Thirty young adults (M=20.7 years) and 31 older adults (M=69.6 years) performed an adapted Hayling task including a switching block (i.e., unblocked design) in addition to the classical task (i.e., blocked design), and the selection of the response between two propositions. The results obtained with the classical blocked design showed age-related deficits in the suppression sections of the task but also in the initiation ones. These findings can be explained by a co-impairment of both inhibition and activation processes in aging. The results of the unblocked Hayling task, in which strategy use would be reduced, confirmed this age-related decline in both activation and inhibition processes. Moreover, significant correlations between the unblocked design and the Trail Making Test revealed that flexibility is equally involved in the completion of both sections of this design. Finally, the use of a forced response choice offers a format that is easy to administer to people with normal or pathological aging. This seems particularly relevant for these populations in whom the production of an unrelated word often poses problems. PMID- 25139229 TI - Arabidopsis thaliana calmodulin-like protein CML24 regulates pollen tube growth by modulating the actin cytoskeleton and controlling the cytosolic Ca(2+) concentration. AB - Cytosolic free calcium ([Ca(2+)]cyt), which is essential during pollen germination and pollen tube growth, can be sensed by calmodulin-like proteins (CMLs). The Arabidopsis thaliana genome encodes over 50 CMLs, the physiological role(s) of most of which are unknown. Here we show that the gene AtCML24 acts as a regulator of pollen germination and pollen tube extension, since the pollen produced by loss-of-function mutants germinated less rapidly than that of wild type (WT) plants, the rate of pollen tube extension was slower, and the final length of the pollen tube was shorter. The [Ca(2+)]cyt within germinated pollen and extending pollen tubes produced by the cml24 mutant were higher than their equivalents in WT plants, and pollen tube extension was less sensitive to changes in external [K(+)] and [Ca(2+)]. The pollen and pollen tubes produced by cml24 mutants were characterized by a disorganized actin cytoskeleton and lowered sensitivity to the action of latrunculin B. The observations support an interaction between CML24 and [Ca(2+)]cyt and an involvement of CML24 in actin organization, thereby affecting pollen germination and pollen tube elongation. PMID- 25139232 TI - Genetics of osteoporosis. AB - Osteoporosis is a skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, which increases susceptibility to fractures. BMD is a complex quantitative trait with normal distribution and seems to be genetically controlled (in 50-90% of the cases), according to studies on twins and families. Over the last 20 years, candidate gene approach and genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that are associated with low BMD, osteoporosis, and osteoporotic fractures. These SNPs have been mapped close to or within genes including those encoding nuclear receptors and WNT-beta-catenin signaling proteins. Understanding the genetics of osteoporosis will help identify novel candidates for diagnostic and therapeutic targets. PMID- 25139230 TI - Seed-specific increased expression of 2S albumin promoter of sesame qualifies it as a useful genetic tool for fatty acid metabolic engineering and related transgenic intervention in sesame and other oil seed crops. AB - The sesame 2S albumin (2Salb) promoter was evaluated for its capacity to express the reporter gusA gene encoding beta-glucuronidase in transgenic tobacco seeds relative to the soybean fad3C gene promoter element. Results revealed increased expression of gusA gene in tobacco seed tissue when driven by sesame 2S albumin promoter. Prediction based deletion analysis of both the promoter elements confirmed the necessary cis-acting regulatory elements as well as the minimal promoter element for optimal expression in each case. The results also revealed that cis-regulatory elements might have been responsible for high level expression as well as spatio-temporal regulation of the sesame 2S albumin promoter. Transgenic over-expression of a fatty acid desaturase (fad3C) gene of soybean driven by 2S albumin promoter resulted in seed-specific enhanced level of alpha-linolenic acid in sesame. The present study, for the first time helped to identify that the sesame 2S albumin promoter is a promising endogenous genetic element in genetic engineering approaches requiring spatio-temporal regulation of gene(s) of interest in sesame and can also be useful as a heterologous genetic element in other important oil seed crop plants in general for which seed oil is the harvested product. The study also established the feasibility of fatty acid metabolic engineering strategy undertaken to improve quality of edible seed oil in sesame using the 2S albumin promoter as regulatory element. PMID- 25139233 TI - Screening of recombinant Escherichia coli using activation of green fluorescent protein as an indicator. AB - A novel cloning vector that can be used to identify recombinant Escherichia coli colonies by activation of the green fluorescent protein gene (GFP) was constructed. Screening using the vector does not require special reagents. The recombinant plasmid activates GFP, and the rate of false-positive results is low. PMID- 25139231 TI - The pineapple AcMADS1 promoter confers high level expression in tomato and Arabidopsis flowering and fruiting tissues, but AcMADS1 does not complement the tomato LeMADS-RIN (rin) mutant. AB - A previous EST study identified a MADS box transcription factor coding sequence, AcMADS1, that is strongly induced during non-climacteric pineapple fruit ripening. Phylogenetic analyses place the AcMADS1 protein in the same superclade as LeMADS-RIN, a master regulator of fruit ripening upstream of ethylene in climacteric tomato. LeMADS-RIN has been proposed to be a global ripening regulator shared among climacteric and non-climacteric species, although few functional homologs of LeMADS-RIN have been identified in non-climacteric species. AcMADS1 shares 67 % protein sequence similarity and a similar expression pattern in ripening fruits as LeMADS-RIN. However, in this study AcMADS1 was not able to complement the tomato rin mutant phenotype, indicating AcMADS1 may not be a functionally conserved homolog of LeMADS-RIN or has sufficiently diverged to be unable to act in the context of the tomato network of interacting proteins. The AcMADS1 promoter directed strong expression of the GUS reporter gene to fruits and developing floral organs in tomato and Arabidopsis thaliana, suggesting AcMADS1 may play a role in flower development as well as fruitlet ripening. The AcMADS1 promoter provides a useful molecular tool for directing transgene expression, particularly where up-regulation in developing flowers and fruits is desirable. PMID- 25139234 TI - Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice. AB - Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor(flox/flox) mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function. PMID- 25139235 TI - WRNIP1 functions upstream of DNA polymerase eta in the UV-induced DNA damage response. AB - WRNIP1 (WRN-interacting protein 1) was first identified as a factor that interacts with WRN, the protein that is defective in Werner syndrome (WS). WRNIP1 associates with DNA polymerase eta (Poleta), but the biological significance of this interaction remains unknown. In this study, we analyzed the functional interaction between WRNIP1 and Poleta by generating knockouts of both genes in DT40 chicken cells. Disruption of WRNIP1 in Poleta-disrupted (POLH(-/-)) cells suppressed the phenotypes associated with the loss of Poleta: sensitivity to ultraviolet light (UV), delayed repair of cyclobutane pyrimidine dimers (CPD), elevated frequency of mutation, elevated levels of UV-induced sister chromatid exchange (SCE), and reduced rate of fork progression after UV irradiation. These results suggest that WRNIP1 functions upstream of Poleta in the response to UV irradiation. PMID- 25139236 TI - Cellular inhibitor of apoptosis protein 1 ubiquitinates endonuclease G but does not affect endonuclease G-mediated cell death. AB - Inhibitors of Apoptosis Proteins (IAPs) are evolutionarily well conserved and have been recognized as the key negative regulators of apoptosis. Recently, the role of IAPs as E3 ligases through the Ring domain was revealed. Using proteomic analysis to explore potential target proteins of DIAP1, we identified Drosophila Endonuclease G (dEndoG), which is known as an effector of caspase-independent cell death. In this study, we demonstrate that human EndoG interacts with IAPs, including human cellular Inhibitor of Apoptosis Protein 1 (cIAP1). EndoG was ubiquitinated by IAPs in vitro and in human cell lines. Interestingly, cIAP1 was capable of ubiquitinating EndoG in the presence of wild-type and mutant Ubiquitin, in which all lysines except K63 were mutated to arginine. cIAP1 expression did not change the half-life of EndoG and cIAP1 depletion did not alter its levels. Expression of dEndoG 54310, in which the mitochondrial localization sequence was deleted, led to cell death that could not be suppressed by DIAP1 in S2 cells. Moreover, EndoG-mediated cell death induced by oxidative stress in HeLa cells was not affected by cIAP1. Therefore, these results indicate that IAPs interact and ubiquitinate EndoG via K63-mediated isopeptide linkages without affecting EndoG levels and EndoG-mediated cell death, suggesting that EndoG ubiquitination by IAPs may serve as a regulatory signal independent of proteasomal degradation. PMID- 25139237 TI - Distribution and baseline values of trace elements in the sediment of Var River catchment, Southeast France. AB - This study reports on the determination of trace element (TE)-Li, As, Co, Cs, Cu, Pb, U, and Zn-and major element (ME)-Si, Al, Fe, Mg, Ca, Mn, Na, and K concentrations in 18 riverbed sediments and a sediment core from the Var River catchment using inductively coupled plasma mass spectrometry (ICP-MS). The results were compared with those of a reference sediment core, and the contribution of clay and organic carbon contents in the distribution of TE and ME in the sediment samples was investigated. The mean concentrations of the ME were comparable in both core and riverbed samples and were within the natural averages. In the case of TE, the concentrations were lower in riverbed sediment samples than those found in the sediment core. High mean concentration of As was observed (7.6 MUg g(-1)) in both core and riverbed sediments, relatively higher than the worldwide reported values. The obtained data indicated that the natural high level of arsenic might be originated from the parent rocks, especially metamorphic rocks surrounding granites and from Permian sediments. Statistical approach, viz., Pearson correlation matrix, was applied to better understand the correlation among TE in both riverbed and sediment core samples. No significant metallic contamination was detected in the low Var valley despite of the localization of several industrial facilities. Therefore, results confirm that the concentrations of the TE obtained in the riverbed sediments could be considered as a baseline guide for future pollution monitoring program. PMID- 25139238 TI - Soil response to a 3-year increase in temperature and nitrogen deposition measured in a mature boreal forest using ion-exchange membranes. AB - The projected increase in atmospheric N deposition and air/soil temperature will likely affect soil nutrient dynamics in boreal ecosystems. The potential effects of these changes on soil ion fluxes were studied in a mature balsam fir stand (Abies balsamea [L.] Mill) in Quebec, Canada that was subjected to 3 years of experimentally increased soil temperature (+4 degrees C) and increased inorganic N concentration in artificial precipitation (three times the current N concentrations using NH4NO3). Soil element fluxes (NO3, NH4, PO4, K, Ca, Mg, SO4, Al, and Fe) in the organic and upper mineral horizons were monitored using buried ion-exchange membranes (PRSTM probes). While N additions did not affect soil element fluxes, 3 years of soil warming increased the cumulative fluxes of K, Mg, and SO4 in the forest floor by 43, 44, and 79 %, respectively, and Mg, SO4, and Al in the mineral horizon by 29, 66, and 23 %, respectively. We attribute these changes to increased rates of soil organic matter decomposition. Significant interactions of the heating treatment with time were observed for most elements although no clear seasonal patterns emerged. The increase in soil K and Mg in heated plots resulted in a significant but small K increase in balsam fir foliage while no change was observed for Mg. A 6-15 % decrease in foliar Ca content with soil warming could be related to the increase in soil-available Al in heated plots, as Al can interfere with the root uptake of Ca. PMID- 25139240 TI - Applications of time-domain spectroscopy to electron-phonon coupling dynamics at surfaces. AB - Photochemistry is one of the most important branches in chemistry to promote and control chemical reactions. In particular, there has been growing interest in photoinduced processes at solid surfaces and interfaces with liquids such as water for developing efficient solar energy conversion. For example, photoinduced charge transfer between adsorbates and semiconductor substrates at the surfaces of metal oxides induced by photogenerated holes and electrons is a core process in photovoltaics and photocatalysis. In these photoinduced processes, electron phonon coupling plays a central role. This paper describes how time-domain spectroscopy is applied to elucidate electron-phonon coupling dynamics at metal and semiconductor surfaces. Because nuclear dynamics induced by electronic excitation through electron-phonon coupling take place in the femtosecond time domain, the pump-and-probe method with ultrashort pulses used in time-domain spectroscopy is a natural choice for elucidating the electron-phonon coupling at metal and semiconductor surfaces. Starting with a phenomenological theory of coherent phonons generated by impulsive electronic excitation, this paper describes a couple of illustrative examples of the applications of linear and nonlinear time-domain spectroscopy to a simple adsorption system, alkali metal on Cu(111), and more complex photocatalyst systems. PMID- 25139239 TI - Identifying fecal pollution sources using 3M(TM) Petrifilm (TM) count plates and antibiotic resistance analysis in the Horse Creek Watershed in Aiken County, SC (USA). AB - Sources of fecal coliform pollution in a small South Carolina (USA) watershed were identified using inexpensive methods and commonly available equipment. Samples from the upper reaches of the watershed were analyzed with 3M(TM) Petrifilm(TM) count plates. We were able to narrow down the study's focus to one particular tributary, Sand River, that was the major contributor of the coliform pollution (both fecal and total) to a downstream reservoir that is heavily used for recreation purposes. Concentrations of total coliforms ranged from 2,400 to 120,333 cfu/100 mL, with sharp increases in coliform counts observed in samples taken after rain events. Positive correlations between turbidity and fecal coliform counts suggested a relationship between fecal pollution and stormwater runoff. Antibiotic resistance analysis (ARA) compared antibiotic resistance profiles of fecal coliform isolates from the stream to those of a watershed specific fecal source library (equine, waterfowl, canines, and untreated sewage). Known fecal source isolates and unknown isolates from the stream were exposed to six antibiotics at three concentrations each. Discriminant analysis grouped known isolates with an overall average rate of correct classification (ARCC) of 84.3 %. A total of 401 isolates from the first stream location were classified as equine (45.9 %), sewage (39.4 %), waterfowl (6.2 %), and feline (8.5 %). A similar pattern was observed at the second sampling location, with 42.6 % equine, 45.2 % sewage, 2.8 % waterfowl, 0.6 % canine, and 8.8 % feline. While there were slight weather-dependent differences, the vast majority of the coliform pollution in this stream appeared to be from two sources, equine and sewage. This information will contribute to better land use decisions and further justify implementation of low-impact development practices within this urban watershed. PMID- 25139241 TI - Patient-reported outcomes in long-term survivors of metastatic colorectal cancer needing liver resection. AB - BACKGROUND: Five-year survival after hepatic resection for colorectal cancer (CRC) liver metastases is good, but data on patient-reported outcomes are lacking. This study describes the long-term impact of liver surgery for CRC metastases on patient-reported outcomes. METHODS: The study used the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the disease-specific module, EORTC QLQ-LMC21. For functional scales, mean scores out of 100 with 95 per cent c.i. were calculated; differences of 10 points or more were considered clinically significant. Responses to symptom scales and items were categorized as 'minimal' or 'severe'. Proportions and 95 per cent c.i. for symptoms were calculated. RESULTS: A total of 241 patients were recruited; nine (3.7 per cent) had unresectable disease and were excluded. Some 68 (42 men) of 80 long-term survivors participated; their mean age was 69.5 years and median follow-up was 8.0 (range 6.9-9.2) years. Values for baseline and 1-year patient-reported outcome data were similar. Scores for functional scales were excellent (emotional function: 92, 95 per cent c.i. 87 to 96; social function: 94, 89 to 99; role function: 94, 90 to 98), reflecting clinically significant improvements from baseline values of 17 (10 to 24), 12 (3 to 21) and 12 (3 to 20) respectively. Severe symptoms were uncommon (affected less than 5 per cent of patients) for most patient-reported outcome scales or items, but persistent severe symptoms were noted for sexual function (2 per cent increase from baseline), peripheral neuropathy (2 per cent increase), constipation (10 per cent increase) and diarrhoea (5 per cent increase). CONCLUSION: Long-term survivors of metastatic colorectal cancer who have undergone liver surgery have excellent global quality of life, high levels of function and few symptoms. PMID- 25139242 TI - Changeable naevi in people at high risk for melanoma. AB - BACKGROUND AND OBJECTIVES: Naevi may change in size, shape and colour due to multiple inherent and external factors. We observed naevi changing size in adults at high risk of melanoma, and assessed associations of change with demographic factors, skin type, sites of naevi and history of melanoma. METHODS: In total, 29 participants with a personal or first-degree family history of melanoma or those deemed at high risk with multiple naevi of variable morphologies had all melanocytic naevi 0.5-1 cm imaged and their maximum diameter recorded. Maximum diameters from repeat imaging of naevi 12 months later were compared to baseline measurements. Newly appearing naevi >=5 mm and naevi that grew or decreased in size by 20% or more were defined as changeable naevi. Associations between changeable naevi and participants' age, sex, skin type, body sites of naevi and personal and family history of melanoma were assessed. RESULTS: There was no difference in changeable naevus rates among sex, age or skin type. Among the body sites, the head and neck were most likely to have changeable naevi, and the upper limbs the least likely. A family history of melanoma almost tripled the likelihood of having changeable naevi compared with those without both personal and family melanoma history. CONCLUSIONS: Naevi can continue to change in size throughout adulthood, showing both increases and decreases in size as well as the appearance of new naevi. This has important clinical implications, in particular for sequential body imaging used for the detection of melanoma. PMID- 25139243 TI - The functional coupling of the deep abdominal and paraspinal muscles: the effects of simulated paraspinal muscle contraction on force transfer to the middle and posterior layer of the thoracolumbar fascia. AB - The thoracolumbar fascia (TLF) consists of aponeurotic and fascial layers that interweave the paraspinal and abdominal muscles into a complex matrix stabilizing the lumbosacral spine. To better understand low back pain, it is essential to appreciate how these muscles cooperate to influence lumbopelvic stability. This study tested the following hypotheses: (i) pressure within the TLF's paraspinal muscular compartment (PMC) alters load transfer between the TLF's posterior and middle layers (PLF and MLF); and (ii) with increased tension of the common tendon of the transversus abdominis (CTrA) and internal oblique muscles and incremental PMC pressure, fascial tension is primarily transferred to the PLF. In cadaveric axial sections, paraspinal muscles were replaced with inflatable tubes to simulate paraspinal muscle contraction. At each inflation increment, tension was created in the CTrA to simulate contraction of the deep abdominal muscles. Fluoroscopic images and load cells captured changes in the size, shape and tension of the PMC due to inflation, with and without tension to the CTrA. In the absence of PMC pressure, increasing tension on the CTrA resulted in anterior and lateral movement of the PMC. PMC inflation in the absence of tension to the CTrA resulted in a small increase in the PMC perimeter and a larger posterior displacement. Combining PMC inflation and tension to the CTrA resulted in an incremental increase in PLF tension without significantly altering tension in the MLF. Paraspinal muscle contraction leads to posterior displacement of the PLF. When expansion is combined with abdominal muscle contraction, the CTrA and internal oblique transfers tension almost exclusively to the PLF, thereby girdling the paraspinal muscles. The lateral border of the PMC is restrained from displacement to maintain integrity. Posterior movement of the PMC represents an increase of the PLF extension moment arm. Dysfunctional paraspinal muscles would reduce the posterior displacement of the PLF and increase the compliance of the lateral border. The resulting change in PMC geometry could diminish any effects of increased tension of the CTrA. This study reveals a co-dependent mechanism involving balanced tension between deep abdominal and lumbar spinal muscles, which are linked through the aponeurotic components of the TLF. This implies the existence of a point of equal tension between the paraspinal muscles and the transversus abdominis and internal oblique muscles, acting through the CTrA. PMID- 25139244 TI - Susceptibility of Escherichia coli to the toxic L-proline analogue L selenaproline is dependent on two L-cystine transport systems. AB - AIMS: L-Selenaproline (L-selenazolidine-4-carboxylic acid) is a toxic analogue of L-proline that inhibits the growth of the urinary tract pathogen Escherichia coli in both laboratory culture media and normal human urine. The aim of this study was to identify the transport systems involved in its uptake. METHODS AND RESULTS: Deletion mutants from the Keio collection were tested for their susceptibility to L-selenaproline (SCA) and L-selenocystine (SeCys) on minimal salts agar medium. All single-gene mutants were sensitive to both compounds, but double mutants with deletions in fliY and ydjN or in yecS and ydjN were resistant to SCA and SeCys. The YdjN transporter active in strain JW1905 (DeltafliY::kan yecC(+) yecS(+) ydjN(+)) was inhibited by both SCA and SeCys, but the FliY YecS YecC ABC transporter system active in strain JW1718 (fliY(+) yecC(+) yecS(+) DeltaydjN::kan) was best inhibited by these compounds in the presence of dithiothreitol. CONCLUSIONS: L-selenaproline and L-selenocystine are accumulated by both the FliY YecC YecS and the YdjN L-cystine transporter systems in E. coli. SIGNIFICANCE AND IMPACT OF THE STUDY: Because susceptibility to selenium containing analogues of L-proline and L-cystine is dependent on multiple transport systems, these compounds may be effective in the treatment of urinary tract infections. PMID- 25139245 TI - Pressure mat analysis of naturally occurring lameness in young pigs after weaning. AB - BACKGROUND: Lameness is a common problem in modern swine husbandry. It causes welfare problems in affected pigs as well as financial problems for farmers. To minimize these negative consequences of lameness, new treatment and prevention strategies need to be developed and validated using objective and quantitative measurement techniques. An example of such a putative diagnostic tool is the use of a pressure mat. Pressure mats are able to provide both objective loading (kinetic) as well as objective movement (kinematic) information on pig locomotion.In this study, pressure mat analysis was used to assess compensatory force redistribution in lame pigs; in particular a predefined set of four pressure mat parameters was evaluated for its use to objectively distinguish clinically lame from sound pigs. Kinetic data from 10 clinically lame and 10 healthy weaned piglets were collected. These data were analyzed to answer three research questions. Firstly the pattern of compensatory weight distribution in lame animals was studied using the asymmetry indices (ASI) for several combinations of limbs. Secondly, the correlation between total left-right asymmetry index and visual scores of lameness was assessed. Thirdly, by using receiver-operated curve (ROC) analysis, optimal cutoff values for these ASIs were then calculated to objectively detect lame pigs. RESULTS: Lame animals generally showed a shift in loading towards their diagonal and contralateral limbs, resulting in a clear left-right asymmetry. The degree of lameness as graded by visual scoring correlated well with the total left-right ASIs. Lame pigs could be objectively distinguished from sound pigs based on clear cutoff points calculated by ROC analysis for the complete set of four evaluated parameters. CONCLUSIONS: The gait of lame pigs is asymmetric, due to the unloading of the affected limb and concomitant weight redistribution towards other limbs. This asymmetry objectively expressed as total left-right asymmetry, correlates well with the subjective visual lameness scoring and can be used to objectively distinguish lame from sound pigs. Pressure mat gait analysis of pigs, therefore, appears to be a promising and useful tool to objectively quantify and possibly early detect lameness in pigs. PMID- 25139246 TI - Retrograde closure of perimembranous ventricular septal defect using muscular ventricular septal occluder: a single-center experience of a novel technique. AB - We herein report the advantages of retrograde ventricular septal defect (VSD) closure using a muscular VSD device for perimembranous VSDs. Perimembranous VSDs are conventionally closed by an antegrade technique (arteriovenous looping technique) using a patent ductus arteriosus or asymmetric perimembranous VSD device. However, we used a symmetrical muscular VSD device in all cases described in this report. Use of the antegrade technique for the first few patients with VSD resulted in prolonged procedural and fluoroscopic times and frequent slippage of the device into the right ventricle. Subsequent use of the retrograde technique shortened the procedural time and allowed for easier closure of the perimembranous VSD. We performed retrograde closure of perimembranous VSDs using a symmetrical muscular VSD device in 130 patients. We obtained a high rate of successful deployment (88.5%) and a low rate of complications (6.0%). We also achieved shorter procedural and fluoroscopic times than those associated with the antegrade technique. PMID- 25139250 TI - Has the Diagnostic and statistical manual of mental illnesses (fifth edition) jumped the shark and is it now time for Australia to reconsider reliance on it? AB - OBJECTIVE: The purpose of this article is to consider whether, in light of the significant controversy surrounding the Diagnostic and statistical manual of mental illnesses (fifth edition) (DSM-5), it may be time for Australia to reconsider the influence of, and its past reliance on, the DSM. Also considered is whether it is now time, with the imminent publication of the The international statistical classification of diseases and related health problems (eleventh edition) (ICD-11), to move to the ICD-11 as the primary instrument for diagnosis and research in Australia. CONCLUSION: That DSM-5 begins its life in an unprecedented plethora of criticism, not only from lay people but also from mental health professionals, which should sound a note of caution for continued reliance on it in Australia. PMID- 25139249 TI - Oxidant-free dehydrogenative coupling reactions via hydrogen evolution. AB - Oxidant-free dehydrogenative coupling reactions: Recently, coupling reactions have followed a novel strategy for the construction of C==C, C==N, C==P, and S==S bonds by dehydrogenation without using any extra oxidant, via H2 evolution. These breakthroughs inspire a new direction in the construction of chemical bonds, towards more sustainable, highly atom-economical, and environmentally benign synthetic methods. PMID- 25139252 TI - Investigation into the structural composition of hydroalcoholic solutions as basis for the development of multiple suppression pulse sequences for NMR measurement of alcoholic beverages. AB - An eight-fold suppression pulse sequence was recently developed to improve sensitivity in (1) H NMR measurements of alcoholic beverages [Magn. Res. Chem. 2011 (49): 734-739]. To ensure that only one combined hydroxyl peak from water and ethanol appears in the spectrum, adjustment to a certain range of ethanol concentrations was required. To explain this observation, the structure of water ethanol solutions was studied. Hydroalcoholic solutions showed extreme behavior at 25% vol, 46% vol, and 83% vol ethanol according to (1) H NMR experiments. Near infrared spectroscopy confirmed the occurrence of four significant compounds ('individual' ethanol and water structures as well as two water-ethanol complexes of defined composition - 1 : 1 and 1 : 3). The successful multiple suppression can be achieved for every kind of alcoholic beverage with different alcoholic strengths, when the final ethanol concentration is adjusted to a range between 25% vol and 46% vol (e.g. using dilution or pure ethanol addition). In this optimum region, an individual ethanol peak was not detected, because the 'individual' water structure and the 1 : 1 ethanol-water complex predominate. The nature of molecular association in ethanol-water solutions is essential to elucidate NMR method development for measurement of alcoholic beverages. The presented approach can be used to optimize other NMR suppression protocols for binary water-organic solvent mixtures, where hydrogen bonding plays a dominant role. PMID- 25139251 TI - Continuous regional anaesthesia provides effective pain management and reduces opioid requirement following major lower limb amputation. AB - OBJECTIVES: Postoperative stump pain after major lower limb amputation is a significant impediment to the recovery of amputees. The vast majority of patients require opioid analgesics following surgery, which are associated with opioid related side-effects. Here, we investigate whether intraoperative placement of a peripheral nerve stump catheter followed by continuous infusion of local anesthetic is as effective at pain control as current analgesic practices. If beneficial, this procedure could potentially reduce post-amputation opioid consumption and opioid-related adverse effects. METHODS: A retrospective chart review was conducted of 198 patients over a 4-year period who had undergone a major lower limb amputation for indications related to peripheral vascular disease. Postoperatively, 102 patients received a perineural catheter were compared to 96 patients who did not. The primary outcomes of this study were the amount of morphine equivalents used in the first 72 hours postoperatively and postoperative pain intensity in the first 24 hours. RESULTS: A total of 198 lower limb amputations were selected for analyses. Multiple regression analyses indicated that perineural catheter use was associated with a lower cumulative postoperative opioid consumption over the first 72 hours but not postoperative pain scores at 24 hours. Perineural catheter use led to a 40% reduction in opioid use during the first 72 hours postoperatively. Mixed model repeated measures analysis demonstrated that this opioid reduction was consistent over time. Other variables related to total opioid use included age, pre-surgical chronic pain, pre-surgical opioid use, patient-controlled analgesia. CONCLUSIONS: Continuous perineural infusions of local anesthetic are a safe and effective method for reducing post-amputation opioid analgesic medications after major lower limp amputation. PMID- 25139247 TI - Williams-Beuren syndrome: computed tomography imaging review. AB - Williams-Beuren syndrome (WBS) affects young infants and children. The underlying etiopathogenesis of this rare disease is due to the mutation of the elastin gene that is responsible for the elasticity of the arterial wall. As a result of inadequate elastin production, the major systemic arteries become abnormally rigid and can be manifested by an impediment to the blood flow. The most common cardiovascular abnormalities encountered in WBS are supravalvular aortic stenosis, pulmonary arterial stenosis, and mitral valve prolapse. Less frequently observed cardiovascular abnormalities include coarctation of the aorta, ventricular septal defect, patent ductus, subaortic stenosis, and hypertrophic cardiomyopathy. Coronary artery stenosis and severe impediment to the bi ventricular outflow as a result of supravalvular aortic and pulmonary artery stenosis predispose patients to sudden death. Patients with progressed arterial stenosis and severe stenosis are likely to require intervention to prevent serious complications. Rarely, imaging findings may precede clinical presentation, which allows the radiologist to participate in the patient care. However, to be more prudent, the radiologist must be accustomed to the imaging characteristics of WBS as well as the patient's clinical information, which could raise the suspicion of WBS. We performed a retrospective analysis of all the available images from patients diagnosed with WBS in last 4 years at our institution, and present key imaging findings along with a review of the literature to summarize the clinically relevant features as demonstrated by multidetector computed tomography in WBS. Cross-sectional imaging plays a vital role in the diagnosis of WBS cases with equivocal clinical features. MDCT evaluation of complex cardiovascular abnormalities of WBS including coronary artery disease is feasible with modern MDCT scanners and in the future, this approach could provide accurate information for planning, navigation, and noninvasive assessment of the secondary arterial changes in WBS and thus reducing the dependence upon invasive contrast catherization techniques. PMID- 25139253 TI - Symptomatic hypercalcemia in a rabies survivor underwent hemodialysis. AB - Adrenal insufficiency is an uncommon and easily ignored cause among most etiologies of hypercalcemia because not all cases of adrenal insufficiency presented with hypercalcemia. In most cases of adrenal insufficiency, viral encephalitis-related panhypopituitarism is a rare complication that is sporadically encountered in previous studies. However, this complication has never been reported in rabies encephalitis because of the extremely high rate of mortality. Rapid recovery from hypercalcemia state after glucocorticoid supplement is a direct hint of adrenal insufficiency related hypercalcemia. PMID- 25139254 TI - Identification of an MLL4-GPS2 fusion as an oncogenic driver of undifferentiated spindle cell sarcoma in a child. AB - Undifferentiated spindle cell sarcoma (UDS) is a poorly defined or understood entity, essentially a waste-basket for cases failing to fulfill criteria for better-established diagnoses based on combined histology, immunohistochemistry, and tumor genetic assays. We identified a novel chromosomal translocation t(17;19)(p13;q13) in a pediatric UDS and have characterized this alteration to show rearrangement of the MLL4 and GPS2 genes, resulting in an in-frame fusion gene MLL4-GPS2, the expression of which promotes anchorage-independent growth. MLL4 was previously reported to be similarly rearranged in hepatocellular carcinomas, notably those positive for hepatitis B virus. Isolated reports of individual rearrangements of GPS2 in a prostate carcinoma cell line and in glioblastoma multiforme, each with different partner genes, recently emerged from high-throughput sequencing studies but have not been further evaluated for biological effect. PMID- 25139255 TI - Dismal outcome of acute myeloid leukemia secondary to myelodysplastic syndrome and chronic myelomonocytic leukemia after azacitidine failure in a daily-life setting. PMID- 25139256 TI - Systematic reviews addressing identified health policy priorities in Eastern Mediterranean countries: a situational analysis. AB - BACKGROUND: Systematic reviews can offer policymakers and stakeholders concise, transparent, and relevant evidence pertaining to pressing policy priorities to help inform the decision-making process. The production and the use of systematic reviews are specifically limited in the Eastern Mediterranean region. The extent to which published systematic reviews address policy priorities in the region is still unknown. This situational analysis exercise aims at assessing the extent to which published systematic reviews address policy priorities identified by policymakers and stakeholders in Eastern Mediterranean region countries. It also provides an overview about the state of systematic review production in the region and identifies knowledge gaps. METHODS: We conducted a systematic search of the Health System Evidence database to identify published systematic reviews on policy-relevant priorities pertaining to the following themes: human resources for health, health financing, the role of the non-state sector, and access to medicine. Priorities were identified from two priority-setting exercises conducted in the region. We described the distribution of these systematic reviews across themes, sub-themes, authors' affiliations, and countries where included primary studies were conducted. RESULTS: Out of the 1,045 systematic reviews identified in Health System Evidence on selected themes, a total of 200 systematic reviews (19.1%) addressed the priorities from the Eastern Mediterranean region. The theme with the largest number of systematic reviews included was human resources for health (115) followed by health financing (33), access to medicine (27), and role of the non-state sector (25). Authors based in the region produced only three systematic reviews addressing regional priorities (1.5%). Furthermore, no systematic review focused on the Eastern Mediterranean region. Primary studies from the region had limited contribution to systematic reviews; 17 systematic reviews (8.5%) included primary studies conducted in the region. CONCLUSIONS: There are still gaps in the production of systematic reviews addressing policymakers' and stakeholders' priorities in the Eastern Mediterranean region. Efforts should be directed towards better aligning systematic review production with policy needs and priorities. Study findings can inform the agendas of researchers, research institutions, and international funding agencies of priority areas where systematic reviews are required. PMID- 25139257 TI - The efficacy of an intervention for the management of postpartum fatigue. AB - OBJECTIVE: To assess the efficacy of a psychoeducational intervention, Wide Awake Parenting (WAP), to decrease symptoms of postnatal fatigue. DESIGN: A randomized controlled trial. SETTING: Local government areas within the Australian state of Victoria. PARTICIPANTS: Two hundred and two mothers were randomly allocated to either the professionally-led telephone support intervention (n = 63), self directed written intervention (n = 67), or waitlist control (n = 72). METHODS: The professionally-led group received a workbook, home visit, and three telephone support calls. The self-directed written group received the workbook only, and the control group received usual health care services. Primary outcomes were symptoms of fatigue, depression, anxiety and stress, and health care beliefs and behaviors. Mothers were followed up at 2- and 6-weeks postintervention. RESULTS: Mothers in the professionally-led group reported fewer symptoms of fatigue than mothers in the control condition at 6 weeks postintervention. Mothers in either intervention had more positive attitudes toward their health- and self-care behaviors at postintervention and follow-up. Mothers in the professionally-led intervention reported fewer symptoms of depression, anxiety, and stress than mothers in the other conditions at postintervention. CONCLUSION: Wide Awake Parenting is effective in promoting mothers' self-efficacy to prioritize, plan for, and engage in health and self-care behaviors to promote mental health and manage fatigue. Implications and future opportunities for WAP are discussed. PMID- 25139258 TI - PARP inhibitor olaparib increases the oncolytic activity of dl922-947 in in vitro and in vivo model of anaplastic thyroid carcinoma. AB - PARP inhibitors are mostly effective as anticancer drugs in association with DNA damaging agents. We have previously shown that the oncolytic adenovirus dl922-947 induces extensive DNA damage, therefore we hypothesized a synergistic antitumoral effect of the PARP inhibitor olaparib in association with dl922-947. Anaplastic thyroid carcinoma was chosen as model since it is a particularly aggressive tumor and, because of its localized growth, it is suitable for intratumoral treatment with oncolytic viruses. Here, we show that dl922-947 infection induces PARP activation, and we confirm in vitro and in vivo that PARP inhibition increases dl922-947 replication and oncolytic activity. In vitro, the combination with olaparib exacerbates the appearance of cell death markers, such as Annexin V positivity, caspase 3 cleavage, cytochrome C release and propidium iodide permeability. In vivo, we also observed a better viral distribution upon PARP inhibition. Changes in CD31 levels suggest a direct effect of olaparib on tumor vascularization and on the viral distribution within the tumor mass. The observation that PARP inhibition enhances the effects of dl922-947 is highly promising not only for the treatment of anaplastic thyroid carcinoma but, in general, for the treatment of other tumors that could benefit from the use of oncolytic viruses. PMID- 25139261 TI - Surface plasmon enhancement of broadband photoluminescence emission from graphene oxide. AB - The photoluminescence (PL) emission studies of both graphene oxide (GO) and partially reduced graphene oxide (rGO) have been investigated. It has been observed that GO has broadband emission from the green to near infrared range and upon reduction rGO shows blue PL emission. The broadband PL emission is due to the recombination of the electron-hole pair in the sp(2) domain embedded within the sp(3) matrix. The broadband PL emission also suggests the existence of various sizes of the sp(2) domain within the same matrix. Furthermore, PL emission from GO in the presence of an Au metal thin film has been investigated. It has been observed that the entire broadband emission from GO in the green to near infrared wavelength region is enhanced significantly at room temperature. The Au-GO interface exhibits surface plasmon resonance in the visible wavelength region and is responsible for over 10 fold enhancement in the photoluminescence at ~2.36 eV. The electrical property measurements on the GO and rGO thin films suggested that the rGO exhibits significantly higher electrical conductivity compared to that of the GO thin film. Furthermore, the GO thin film exhibits semiconducting behaviour. These properties make the material quite suitable for fabrication of new generation photonic devices. PMID- 25139259 TI - Evolution of the central sulcus morphology in primates. AB - The central sulcus (CS) divides the pre- and postcentral gyri along the dorsal ventral plane of which all motor and sensory functions are topographically organized. The motor-hand area of the precentral gyrus or KNOB has been described as the anatomical substrate of the hand in humans. Given the importance of the hand in primate evolution, here we examine the evolution of the motor-hand area by comparing the relative size and pattern of cortical folding of the CS surface area from magnetic resonance images in 131 primates, including Old World monkeys, apes and humans. We found that humans and great apes have a well-formed motor hand area that can be seen in the variation in depth of the CS along the dorsal ventral plane. We further found that great apes have relatively large CS surface areas compared to Old World monkeys. However, relative to great apes, humans have a small motor-hand area in terms of both adjusted and absolute surface areas. PMID- 25139260 TI - Development and scale-up of a commercial fed batch refolding process for an anti CD22 two chain immunotoxin. AB - We describe the development and scale-up of a novel two chain immunotoxin refolding process. This work provides a case study comparing a clinical manufacturing process and the commercial process developed to replace it. While the clinical process produced high quality material, it suffered from low yield and high yield variability. A systematic approach to process development and understanding led to a number of improvements that were implemented in the commercial process. These include a shorter inclusion body recovery process, limiting the formation of an undesired deamidated species and the implementation of fed batch dilution refolding for increased refold titers. The use of a combination of urea, arginine and DTT for capture column cleaning restored the binding capacity of the capture step column and resulted in consistent capture step yields compared to the clinical process. Scalability is shown with data from 250 L and 950 L scale refolding processes. Compared to the clinical process it replaces, the commercial process demonstrated a greater than fivefold improvement in volumetric productivity at the 950 L refolding scale. PMID- 25139262 TI - A content analysis of weight stigmatization in popular television programming for adolescents. AB - OBJECTIVE: This study provides updated information regarding the prevalence and characteristics of weight stigma in popular adolescent television programming, using a sample of favorite shows named by diverse adolescents. METHOD: Participants in a large, population-based study of Minnesota adolescents (N = 2,793, mean age = 14.4) listed their top three favorite television shows. A coding instrument was developed to analyze randomly selected episodes from the most popular 10 programs. Weight-stigmatizing incidents were compared across television show characteristics and characters' gender and weight status. RESULTS: Half (50%) of the 30 episodes analyzed contained at least one weight stigmatizing incident. Both youth- and adult-targeted shows contained weight stigmatizing comments, but the percent of these comments was much higher for youth-targeted (55.6%) than general audience-targeted shows (8.3%). Male characters were more likely than females to engage in (72.7% vs. 27.3%), and be the targets of, weight stigma (63.6% vs. 36.4%), and there was no difference in the amount of weight stigmatizing directed at average weight females compared to overweight females. Targets of these instances showed a negative response in only about one-third of cases, but audience laughter followed 40.9% of cases. DISCUSSION: The portrayal of weight stigmatization on popular television shows including targeting women of average weight-sends signals to adolescents about the wide acceptability of this behavior and the expected response, which may be harmful. Prevention of weight stigmatization should take a multi-faceted approach and include the media. Future research should explore the impact that weight related stigma in television content has on viewers. PMID- 25139264 TI - The effects of character transposition within and across words in Chinese reading. AB - Given the lack of spaces between words in Chinese text, Chinese readers must parse these characters into words using their word knowledge. In this situation, are the characters belonging to a single word or to different words understood via different character-order encoding processes? In this study, we explored the effects of word boundaries in Chinese text on character-order encoding. We used four-character words (the one-word condition) and two two-character words (the two-word condition) as our targets. We embedded the target words into sentences and then manipulated the previews of the words using the boundary paradigm. The preview was identical to the target word (identity condition), had the two middle characters of the target word transposed (TC condition), or had two middle characters that were different from those in the target word (SC condition). Fixation durations on the target word in the TC condition were much longer than those in the identity condition for the two-word condition, but they were not significantly different for the one-word condition. Furthermore, for the one-word condition, gaze durations were longer in the SC than in the TC condition, whereas for the two-word condition, the difference between the TC and SC conditions was not significant. Word boundaries were found to affect the character-order encoding in Chinese reading, further suggesting the early occurrence of word segmentation. PMID- 25139263 TI - Investigating the thermostability of succinate: quinone oxidoreductase enzymes by direct electrochemistry at SWNTs-modified electrodes and FTIR spectroscopy. AB - Succinate: quinone reductases (SQRs) are the enzymes that couple the oxidation of succinate and the reduction of quinones in the respiratory chain of prokaryotes and eukaryotes. Herein, we compare the temperature-dependent activity and structural stability of two SQRs, the first from the mesophilic bacterium Escherichia coli and the second from the thermophilic bacterium Thermus thermophilus, using a combined electrochemical and infrared spectroscopy approach. Direct electron transfer was achieved with full membrane protein complexes at single-walled carbon nanotube (SWNT)-modified electrodes. The possible structural factors that contribute to the temperature-dependent activity of the enzymes and, in particular, to the thermostability of the Thermus thermophilus SQR are discussed. PMID- 25139267 TI - Structural basis for the identification of an i-motif tetraplex core with a parallel-duplex junction as a structural motif in CCG triplet repeats. AB - CCG triplet repeats can fold into tetraplex structures, which are associated with the expansion of (CCG)n trinucleotide sequences in certain neurological diseases. These structures are stabilized by intertwining i-motifs. However, the structural basis for tetraplex i-motif formation in CCG triplet repeats remains largely unknown. We report the first crystal structure of a CCG-repeat sequence, which shows that two dT(CCG)3 A strands can associate to form a tetraplex structure with an i-motif core containing four C:C(+) pairs flanked by two G:G homopurine base pairs as a structural motif. The tetraplex core is attached to a short parallel-stranded duplex. Each hairpin itself contains a central CCG loop in which the nucleotides are flipped out and stabilized by stacking interactions. The helical twists between adjacent cytosine residues of this structure in the i motif core have an average value of 30 degrees , which is greater than those previously reported for i-motif structures. PMID- 25139265 TI - 2-(trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate suppresses osteoclast maturation and bone resorption by targeting macrophage colony stimulating factor signaling. AB - 2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R) TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R) TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity. PMID- 25139266 TI - Upregulation of miR-760 and miR-186 is associated with replicative senescence in human lung fibroblast cells. AB - We have previously shown that microRNAs (miRNAs) miR-760, miR-186, miR-337-3p, and miR-216b stimulate premature senescence through protein kinase CK2 (CK2) down regulation in human colon cancer cells. Here, we examined whether these four miRNAs are involved in the replicative senescence of human lung fibroblast IMR-90 cells. miR-760 and miR-186 were significantly upregulated in replicatively senescent IMR-90 cells, and their joint action with both miR-337-3p and miR-216b was necessary for efficient downregulation of the alpha subunit of CK2 (CK2alpha) in IMR-90 cells. A mutation in any of the four miRNA-binding sequences within the CK2alpha 3'-untranslated region (UTR) indicated that all four miRNAs should simultaneously bind to the target sites for CK2alpha downregulation. The four miRNAs increased senescence-associated beta-galactosidase (SA-beta-gal) staining, p53 and p21(Cip1/WAF1) expression, and reactive oxygen species (ROS) production in proliferating IMR-90 cells. CK2alpha over-expression almost abolished this event. Taken together, the present results suggest that the upregulation of miR 760 and miR-186 is associated with replicative senescence in human lung fibroblast cells, and their cooperative action with miR-337-3p and miR-216b may induce replicative senescence through CK2alpha downregulation-dependent ROS generation. PMID- 25139268 TI - Prospective long-term assessment of sedation-related adverse events and patient satisfaction for upper endoscopy and colonoscopy. AB - BACKGROUND: Fear of pain and sedation-related adverse events are impediments for patients to attend endoscopic screening or surveillance programs. OBJECTIVE: To investigate the long-term effect of different sedation protocols in patients undergoing screening or surveillance endoscopy. Moreover, motivation of patients to decline endoscopic procedures was evaluated by focusing on the patient's satisfaction, fear and pain in relation to type of sedation used. METHODS: DESIGN: A prospective, double-blind controlled trial data collection was performed by using a standardized clinical questionnaire followed by a telephone interview 3-4 weeks after the initial endoscopic procedure. SETTING: The study was conducted at the Department of Medicine I at the University Hospital of Erlangen-Nuremberg. Data collection was performed during June 2012 till April 2013. PATIENTS: Overall, 307 patients were prospectively evaluated (44.3% female, mean age 51 +/- 17.4 years; mean BMI 25.5 +/- 5.7). 247 patients (80.5%) were outpatients, 60 inpatients (19.5%). INTERVENTIONS: Endoscopic procedures were divided into five groups: (i) procedures in the upper gastrointestinal tract, (ii) complete colonoscopies, (iii) ileocolonoscopies, (iv) incomplete colonoscopies, and (v) other procedures. MAIN OUTCOME MEASUREMENTS: Patient satisfaction, fear and pain were measured in a structured and standardized clinical interview using a 6-point numerical rating scale, where 1 was 'very satisfied/no pain' and 6 was 'very unsatisfied/unsupportable pain'. RESULTS: Different types of sedation were assessed: propofol in monosedation (6.5%), combination of propofol + meperidine (41.0%), combination of midazolam + meperidine (48.5%) and other combinations (3.9%). Patient satisfaction was significantly reduced regarding fear and pain during the endoscopic procedure (p = 0.001 and p = 0.0001, respectively). All patients receiving propofol monosedation indicated significantly less pain in comparison to other sedation groups (p < 0.0001). Moreover, sedation with midazolam + meperidine increased the fear during the procedure significantly in comparison to monosedation with propofol (p = 0.082). Propofol/meperidine in combination and midazolam/meperidine increased the probability for cardiovascular events in comparison to monosedation with propofol (p = 0.005; p = 0.039). Finally, we observed significantly lower doses of propofol when used in monosedation than propofol in combination with meperidine (p = 0.066). LIMITATION: Single-center study at a tertiary referral center. CONCLUSIONS: Propofol in monosedation should preferably be used for patient sedation in screening and surveillance endoscopies. Whether this approach could also improve participation rates in screening and surveillance endoscopies requires further investigations. PMID- 25139270 TI - Metabolism: sugar on the brain. PMID- 25139269 TI - Endovascular Management of Cavernous Internal Carotid Artery Pseudoaneurysms Following Transsphenoidal Surgery: A Report of Two Cases and Review of the Literature. PMID- 25139273 TI - Oscillations: a dynamic role for astrocytes. PMID- 25139276 TI - Evidence for a radial strain gradient in apple fruit cuticles. AB - MAIN CONCLUSION: The morphological outer side of the apple fruit cuticle is markedly more strained than the inner side. This strain is released upon wax extraction. This paper investigates the effect of ablating outer and inner surfaces of isolated cuticular membranes (CM) of mature apple (Malus * domestica) fruit using cold atmospheric pressure plasma (CAPP) on the release of strain after extraction of waxes. Strain release was quantified as the decrease in area of CM discs following CAPP treatment and subsequent solvent extraction of wax. Increasing duration of CAPP treatment proportionally decreased CM mass per unit area. There was no difference in mass loss rate between CAPP treatments of outer or inner surfaces. Also, there was no difference in surface area of CMs before and after CAPP treatment. However, upon subsequent wax extraction, surface area of CMs decreased indicating the release of strain. Increasing the duration of CAPP treatment resulted in increasing strain release up to 47.7 +/- 8.0 % at 20 min when CAPP was applied to the inner surface. In contrast, strain release was independent of CAPP duration averaging about 12.1 +/- 0.6 % when applied to the outer surface of the CM. Our results provide evidence for a marked gradient of strain between the outer side (strained) and the inner side of the CM (not strained) of mature apple fruit. PMID- 25139278 TI - Having a promising efficacy on type II diabetes, it's definitely a green tea time. AB - The beneficial effects of green tea have been confirmed in various diseases, such as different types of cancer, heart disease, and liver disease. The effective components of green tea mainly include tea polysaccharides and tea polyphenols, such as catechin, particularly (-)-epigallocatechin-3-gallate. Increasing in vivo and in vitro evidences have explored the potential molecular mechanisms of green tea as well as the specific biological actions. Moreover, clinical trials have also explored the potential value of green tea components in treating metabolic syndromes, such as obesity, type II diabetes, and cardiovascular disease. This study explores the effects of the two major green tea components on the improvement of type II diabetes. It is concluded that regular consumption of green tea is beneficial for the improvement of high-fat dietary-induced obesity and type II diabetes. PMID- 25139277 TI - Regulatory control of carotenoid accumulation in winter squash during storage. AB - MAIN CONCLUSION: Storage promotes carotenoid accumulation and converts amylochromoplasts into chromoplasts in winter squash. Such carotenoid enhancement is likely due to continuous biosynthesis along with reduced turnover and/or enhanced sequestration. Postharvest storage of fruits and vegetables is often required and frequently results in nutritional quality change. In this study, we investigated carotenoid storage plastids, carotenoid content, and its regulation during 3-month storage of winter squash butternut fruits. We showed that storage improved visual appearance of fruit flesh color from light to dark orange, and promoted continuous accumulation of carotenoids during the first 2-month storage. Such an increased carotenoid accumulation was found to be concomitant with starch breakdown, resulting in the conversion of amylochromoplasts into chromoplasts. The butternut fruits contained predominantly beta-carotene, lutein, and violaxanthin. Increased ratios of beta-carotene and violaxanthin to total carotenoids were noticed during the storage. Analysis of carotenoid metabolic gene expression and PSY protein level revealed a decreased expression of carotenogenic genes and PSY protein following the storage, indicating that the increased carotenoid level might not be due to increased biosynthesis. Instead, the increase likely resulted from a continuous biosynthesis with a possibly reduced turnover and/or enhanced sequestration, suggesting a complex regulation of carotenoid accumulation during fruit storage. This study provides important information to our understanding of carotenogenesis and its regulation during postharvest storage of fruits. PMID- 25139279 TI - In vivo evaluation of thiolated chitosan tablets for oral insulin delivery. AB - Chitosan-6-mercaptonicotinic acid (chitosan-6-MNA) is a thiolated chitosan with strong mucoadhesive properties and a pH-independent reactivity. This study aimed to evaluate the in vivo potential for the oral delivery of insulin. The comparison of the nonconjugated chitosan and chitosan-6-MNA was performed on several studies such as mucoadhesion, release, and in vivo studies. Thiolated chitosan formulations were both about 80-fold more mucoadhesive compared with unmodified ones. The thiolated chitosan tablets showed a sustained release for 5 h for the polymer of 20 kDa and 8 h for the polymer of 400 kDa. Human insulin was quantified in rats' plasma by means of ELISA specific for human insulin with no cross-reactivity with the endogenous insulin. In vivo results showed thiolation having a tremendous impact on the absorption of insulin. The absolute bioavailabilities were 0.73% for chitosan-6-MNA of 20 kDa and 0.62% for chitosan 6-MNA 400 kDa. The areas under the concentration-time curves (AUC) of chitosan-6 MNA formulations compared with unmodified chitosan were 4.8-fold improved for the polymer of 20 kDa and 21.02-fold improved for the polymer of 400 kDa. The improvement in the AUC with regard to the most promising aliphatic thiomer was up to 6.8-fold. Therefore, chitosan-6-MNA represents a promising excipient for the oral delivery of insulin. PMID- 25139280 TI - alpha-Synuclein Misfolding Versus Aggregation Relevance to Parkinson's Disease: Critical Assessment and Modeling. AB - alpha-Synuclein, an abundant and conserved presynaptic brain protein, is implicated as a critical factor in Parkinson's disease (PD). The aggregation of alpha-synuclein is believed to be a critical event in the disease process. alpha Synuclein is characterized by a remarkable conformational plasticity, adopting different conformations depending on the environment. Therefore, it is classified as an "intrinsically disordered protein." Recently, a debate has challenged the view on the intrinsically disordered behavior of alpha-synuclein in the cell. It has been proposed that alpha-synuclein is a stable tetramer with a low propensity for aggregation; however, its destabilization leads to protein misfolding and its aggregation kinetics. In our critical analysis, we discussed about major issues: (i) why alpha-synuclein conformational behavior does not fit into the normal secondary structural characteristics of proteins, (ii) potential amino acids involved in the complexity of misfolding in alpha-synuclein that leads to aggregation, and (iii) the role of metals in misfolding and aggregation. To evaluate the above critical issues, we developed bioinformatics models related to secondary and tertiary conformations, Ramachandran plot, free energy change, intrinsic disordered prediction, solvent accessibility, and FoldIndex pattern. To the best of our knowledge, this is a novel critical assessment to understand the misfolding biology of synuclein and its relevance to Parkinson's disease. PMID- 25139283 TI - A partial differential equation for pseudocontact shift. AB - It is demonstrated that pseudocontact shift (PCS), viewed as a scalar or a tensor field in three dimensions, obeys an elliptic partial differential equation with a source term that depends on the Hessian of the unpaired electron probability density. The equation enables straightforward PCS prediction and analysis in systems with delocalized unpaired electrons, particularly for the nuclei located in their immediate vicinity. It is also shown that the probability density of the unpaired electron may be extracted, using a regularization procedure, from PCS data. PMID- 25139282 TI - The Antidepressant-Like Effect of Fish Oil: Possible Role of Ventral Hippocampal 5-HT1A Post-synaptic Receptor. AB - The pathophysiology of depression is not completely understood; nonetheless, numerous studies point to serotonergic dysfunction as a possible cause. Supplementation with fish oil rich docosahexaenoic (DHA) and eicosapentaenoic acids (EPA) during critical periods of development produces antidepressant effects by increasing serotonergic neurotransmission, particularly in the hippocampus. In a previous study, the involvement of 5-HT1A receptors was demonstrated and we hypothesized that fish oil supplementation (from conception to weaning) alters the function of post-synaptic hippocampal 5-HT1A receptors. To test this hypothesis, female rats were supplemented with fish oil during habituation, mating, gestation, and lactation. The adult male offspring was maintained without supplementation until 3 months of age, when they were subjected to the modified forced swimming test (MFST) after infusion of vehicle or the selective 5-HT1A antagonist, WAY100635, and frequency of swimming, immobility, and climbing was recorded for 5 min. After the behavioral test, the hippocampi were obtained for quantification of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and for 5-HT1A receptor expression by Western blotting analysis. Fish oil-supplemented offspring displayed less depressive-like behaviors in the MFST reflected by decreased immobility and increased swimming and higher 5-HT hippocampal levels. Although there was no difference in the expression of hippocampal 5-HT1A receptors, intra hippocampal infusion of a sub-effective dose of 8-OH-DPAT enhanced the antidepressant effect of fish oil in supplemented animals. In summary, the present findings suggest that the antidepressant-like effects of fish oil supplementation are likely related to increased hippocampal serotonergic neurotransmission and sensitization of hippocampal 5-HT1A receptors. PMID- 25139286 TI - Hexavalent chromium reduction in contaminated soil: A comparison between ferrous sulphate and nanoscale zero-valent iron. AB - Iron sulphate (FeSO4) and colloidal nano zero-valent iron (nZVI) as reducing agents were compared, with the aim of assessing their effectiveness in hexavalent chromium [Cr(VI)] removal from a contaminated industrial soil. Experiments were performed on soil samples collected from an industrial site where a nickel contamination, caused by a long-term productive activity, was also verified. The influence of reducing agents amount with respect to chromium content and the effectiveness of deoxygenation of the slurry were discussed. The soil was fully characterized before and after each test, and sequential extractions were performed to assess chemico-physical modifications and evaluate metals mobility induced by washing. Results show that both the reducing agents successfully lowered the amount of Cr(VI) in the soil below the threshold allowed by Italian Environmental Regulation for industrial reuse. Cr(VI) reduction by colloidal nZVI proved to be faster and more effective: the civil reuse of soil [Cr(VI)<2mg/kg] was only achieved using colloidal nZVI within 60min adopting a nZVI/Cr(VI) molar ratio of 30. The reducing treatment resulted in an increase in the amount of chromium in the oxide-hydroxide fraction, thus confirming a mechanism of chromium iron hydroxides precipitation. In addition, a decrease of nickel (Ni) and lead (Pb) content in soil was also observed when acidic conditions were established. PMID- 25139285 TI - Urgent lung transplant programme in Italy: analysis of the first 14 months. AB - OBJECTIVES: Lung transplantation (LTx) is the only effective treatment for end stage lung disease. In rapidly deteriorating patients awaiting transplant, supportive strategies for lung function allow only a short period of support and lung transplantation remains the definitive therapy. An urgent transplant programme may reduce the waiting time, allowing lung transplantation in these patients. METHODS: Since November 2010 a nation-wide urgent lung transplant programme has been established in Italy and patients on the waiting list dependent on mechanical ventilation and/or extracorporeal lung support (ECLS) can be transplanted on an emergency basis with the first available graft in the country. Results of the first 14 months of this programme are analysed here. RESULTS: From November 2010 to December 2011, 28 patients (14 males, mean age 33.6 +/- 14.4 years) were considered for urgent LTx. Rapidly deteriorating lung function was supported with mechanical ventilation alone in 4 patients (14.3%), ECLS in 13 patients (46.4%) and mechanical ventilation plus ECLS in the remaining 11 patients (39.3%). Three patients (10.7%) were excluded because of worsening conditions, 3 patients (10.7%) while on the urgent listed and 22 patients (78.6%) underwent transplantation after 9.8 +/- 6.2 days of being on the urgent list. The 30-day mortality rate after LTx was 18%, and the 1-year survival rate was 71.4%. CONCLUSIONS: The urgent lung transplant programme allowed transplantation in a significant percentage of prioritized patients with acceptable 30-day and 1-year mortality rates. An accurate selection of recipients may further improve the clinical impact of this programme, reducing the ethical concerns about transplantation in high-risk patients. PMID- 25139281 TI - Updated findings of the association and functional studies of DRD2/ANKK1 variants with addictions. AB - Both nicotine and alcohol addictions are severe public health hazards worldwide. Various twin and family studies have demonstrated that genetic factors contribute to vulnerability to these addictions; however, the susceptibility genes and the variants underlying them remain largely unknown. Of susceptibility genes investigated for addictions, DRD2 has received much attention. Considering new evidence supporting the association of DRD2 and its adjacent gene ankyrin repeat and kinase domain containing 1 (ANKK1) with various addictions, in this paper, we provide an updated view of the involvement of variants in DRD2 and ANKK1 in the etiology of nicotine dependence (ND) and alcohol dependence (AD) based on linkage, association, and molecular studies. This evidence shows that both genes are significantly associated with addictions; however the association with ANKK1 appears to be stronger. Thus, both more replication studies in independent samples and functional studies of some of these variants are warranted. PMID- 25139287 TI - The role of telomeres and telomerase in hematologic malignancies and hematopoietic stem cell transplantation. AB - Telomeres are specific nucleoprotein structures at the ends of eukaryotic chromosomes. Telomeres and telomere-associated proteins maintain genome stability by protecting the ends of chromosomes from fusion and degradation. In normal somatic cells, the length of the telomeres gradually becomes shortened with cell division. In tumor cells, the shortening of telomeres length is accelerated under the increased proliferation pressure. However, it will be maintained at an extremely short length as the result of activation of telomerase. Significantly shortened telomeres, activation of telomerase, and altered expression of telomere associated proteins are common features of various hematologic malignancies and are related with progression or chemotherapy resistance in these diseases. In patients who have received hematopoietic stem cell transplantation (HSCT), the telomere length and the telomerase activity of the engrafted donor cells have a significant influence on HSCT outcomes. Transplantation-related factors should be taken into consideration because of their impacts on telomere homeostasis. As activation of telomerase is widespread in tumor cells, it has been employed as a target point in the treatment of neoplastic hematologic disorders. In this review, the characteristics and roles of telomeres and telomerase both in hematologic malignancies and in HSCT will be summarized. The current status of telomerase-targeted therapies utilized in the treatment of hematologic malignancies will also be reviewed. PMID- 25139288 TI - Comparative evaluation of molar distalization therapy with erupted second molar: Segmented versus Quad Pendulum appliance. AB - BACKGROUND: There are controversial opinions about the effect of erupted second molars on distalization of the first molars. Most of the distalizing devices are anchored on the first molars, without including second molars; so, differences between sequentially distalize maxillary molars (second molar followed by the first molar) or distalize second and first molars together are not clear. The aim of the study was to compare sequential versus simultaneous molar distalization therapy with erupted second molar using two different modified Pendulum appliances followed by fixed appliances. METHODS: The treatment sample consisted of 35 class II malocclusion subjects, divided in two groups: group 1 consisted of 24 patients (13 males and 11 females) with a mean pre-treatment age of 12.9 years, treated with the Segmented Pendulum (SP) and fixed appliances; group 2 consisted of 11 patients (6 males and 5 females) with a mean pre-treatment age of 13.2 years, treated with the Quad Pendulum (QP) and fixed appliances. Lateral cephalograms were obtained before treatment (T1), at the end of distalization (T2), and at the end of orthodontic fixed appliance therapy (T3). A Student t test was used to identify significant between-group differences between T1 to T2, T2 to T3, and T1 to T3. RESULTS: QP and SP were equally effective in distalizing maxillary molars (3.5 and 4 mm, respectively) between T1 and T2; however, the maxillary first molar showed less distal tipping (4.6 degrees vs. 9.6 degrees ) and more extrusion (1.1 vs. 0.2 mm) in the QP group than in the SP group, as well as the vertical facial dimension, which increased more in the QP group (1.2 degrees ) than in the SP group (0.7 degrees ). At T3, the QP group maintained greater increase in lower anterior facial height and molar extrusion and decrease in overbite than the SP group. CONCLUSION: Quad Pendulum seems to have greater increase in vertical dimension and molar extrusion than the Segmented Pendulum. PMID- 25139289 TI - NK cells kill mycobacteria directly by releasing perforin and granulysin. AB - Although the mechanisms underlying the cytotoxic effect of NK cells on tumor cells and intracellular bacteria have been studied extensively, it remains unclear how these cells kill extracellular bacterial pathogens. In this study, we examine how human NK cells kill Mycobacterium kansasii and M.tb. The underlying mechanism is contact dependent and requires two cytolytic proteins: perforin and granulysin. Mycobacteria induce enhanced expression of the cytolytic proteins via activation of the NKG2D/NCR cell-surface receptors and intracellular signaling pathways involving ERK, JNK, and p38 MAPKs. These results suggest that NK cells use similar cellular mechanisms to kill both bacterial pathogens and target host cells. This report reveals a novel role for NK cells, perforin, and granulysin in killing mycobacteria and highlights a potential alternative defense mechanism that the immune system can use against mycobacterial infection. PMID- 25139291 TI - Effects of surface wettability on gecko adhesion underwater. AB - Recent experiments have shown that gecko adhesion underwater depends significantly on surface wettability. Theoretical models of a gecko seta adhering on different substrates are firstly established in order to disclose such an adhesion mechanism. The results show that the capillary force induced by nano bubbles between gecko seta and the substrate is the mainly influencing factor. The capillary force exhibits an attractive feature between gecko setae and hydrophobic surfaces underwater. However, it is extremely weak or even repulsive on hydrophilic surfaces underwater. A self-similarly splitting model is further considered to simulate multiple gecko setae on substrates underwater. It is interesting to find that the total capillary force depends significantly on the number of nano-bubble bridges and wettability of substrates. The total force is attractive and increases monotonically with the increase of the splitting number on hydrophobic substrates underwater. However, it decreases drastically or even becomes repulsive on hydrophilic substrates underwater. The present result can not only give a reasonable explanation on the existing experimental observations but also be helpful for the design of novel biomimetic adhesives. PMID- 25139290 TI - The mucosal expression pattern of interferon-epsilon in rhesus macaques. AB - Type I IFNs play an important role in innate and adaptive immunity against viral infections. A novel type I IFN, namely IFN-epsilon, which can protect against vaginal transmission of HSV2 and Chlamydia muridarum bacterial infection, has been described in mice and humans. Nevertheless, the principle cell type and the expression pattern of IFN-epsilon in tissues remain uncertain. In addition, the expression of IFN-epsilon in Indian rhesus macaques (Macaca mulatta) has not been reported. Here, we analyzed IFN-epsilon expression in multiple mucosal sites of uninfected or SIV-infected Indian rhesus macaques using IHCS. We report for the first time the detection of IFN-epsilon expression in situ in the lung, foreskin, vaginal, cervical, and small and large intestinal mucosae of rhesus macaques. We found that the expression of IFN-epsilon was exclusive to the epithelial cells in all of the aforementioned mucosal tissues. Furthermore, the macaque IFN-epsilon sequence in this study revealed that macaque IFN-epsilon is highly conserved among human and other nonhuman primates. Lastly, SIV rectal infection did not significantly alter the expression of IFN-epsilon in rectal mucosae. Together, these findings indicate that IFN-epsilon may function as the first line of defense against the invasion of mucosal pathogens. Further studies should be conducted to examine IFN-epsilon protection against gastrointestinal as well as respiratory infections. PMID- 25139292 TI - In vivo penetration of bare and lipid-coated silica nanoparticles across the human stratum corneum. AB - Skin penetration of silica nanoparticles (NP) currently used in pharmaceutical and cosmetic products is a topic of interest not only to evaluate their possible toxicity, but also to understand their behaviour upon contact with the skin and to exploit their potential positive effects in drug or cosmetic delivery field. Therefore, the present work aimed to elucidate the in vivo mechanism by which amorphous hydrophilic silica NP enter human stratum corneum (SC) through the evaluation of the role played by the nanoparticle surface polarity and the human hair follicle density. Two silica samples, bare hydrophilic silica (B-silica, 162+/-51nm in size) and hydrophobic lipid-coated silica (LC-silica, 363+/-74nm in size) were applied on both the volar and dorsal side of volunteer forearms. Twelve repetitive stripped tapes were removed from the human skin and evaluated for elemental composition by Energy Dispersive X-ray (EDX) analysis and for silicon content by Inductively Coupled Plasma quadrupole Mass Spectrometry (ICP MS). All the stripped tapes revealed nanosized structures generally located in the broad spaces between corneocytes and characterized by the same elemental composition (relative weight percentage of silicon and silicon to oxygen weight ratio) than that of the applied samples. However, only about 10% B-silica permeated until the deepest SC layers considered in the study indicating a silica retention in the upper layers of SC, regardless of the hair follicle density. Otherwise, the exposure to LC-silica led to a greater silica skin penetration extent into the deeper SC layers (about 42% and 18% silica following volar and dorsal forearm application, respectively) indicating that the NP surface polarity played a predominant role on that of their size in determining the route and the extent of penetration. PMID- 25139293 TI - A simple and effective approach for the treatment of dyslipidemia using anionic nanoliposomes. AB - The present study was undertaken to evaluate the anti-dyslipidemic effects of nanoliposomes with different phospholipid compositions. Three sets of liposomal formulations (20Mm; 100nM in size) were prepared with low (SPC), medium (POPC) and high (HSPC) phase transition temperature values with and without cholesterol and anionic phosphatidyl glycerol (HSPC/DSPG; POPC/DMPG; SPC/EPG). The liposomal preparations were characterized for their size and zeta potential (dynamic light scattering), J774A.1 macrophages uptake (flow cytometry) and lipid-modifying effects (tyloxapol-induced hyperlipidemic mouse model). Anionic formulations displayed the highest rate of uptake by macrophages. Among them, HSPC/DSPG and SPC/EPG liposomes had the best lipid-modifying activity. These two formulations exerted favorable impact on all lipid profile parameters by reducing LDL-C (by up to 76% [HSPC/DSPG] and 86% [SPC/EPG]), total cholesterol (by up to 52% [HSPC/DSPG] and 68% [SPC/EPG]), triglycerides (by up to 88% [HSPC/DSPG] and 73% [SPC/EPG]), apoB (by up to 44% [HSPC/DSPG] and 35% [SPC/EPG]) and elevating HDL-C (by up to 85% [HSPC/DSPG] and 75% [SPC/EPG]) concentrations. Atherogenic indices were also effectively reduced following HSPC/DSPG (by up to 69%) and SPC/EPG (by up to 79%) injections. Empty, cholesterol-free nanoliposomal formulations containing 75% anionic phospholipid (PG) might serve as effective and rapid acting anti-dyslipidemic agents. Further research is warranted to confirm the observed anti-dyslipidemic effects of anionic nanoliposomes in diet-induced hyperlipidemic models, and also to evaluate the potential protective effects in regressing atheromatous lesions. PMID- 25139294 TI - Biomarkers for personalizing omega-3 fatty acid dosing. AB - Prostaglandin E2 (PGE2) has been linked to a higher risk of colorectal cancer. PGE2 in colon tissue can be reduced by increasing dietary eicosapentaenoic acid (EPA). The dose-dependent relationships between dietary EPA, serum EPA:arachidonate (AA) ratio, urinary PGE2 metabolites, and colonic eicosanoids were evaluated to develop biomarkers for prediction of colonic PGE2. Male rats were fed diets containing EPA:omega6 fatty acid ratios of 0, 0.1, 0.2, 0.4, or 0.6 for 5 weeks. Increasing the dietary EPA:omega6 fatty acid ratio increased EPA:AA ratios in serum and in the proximal, transverse, and distal colon (P < 0.001). The urinary PGE2 metabolite was reduced (P = 0.006). EPA-rich diets reduced colonic tissue PGE2 concentrations by 58% to 66% and increased PGE3 by 19 to 28-fold. Other AA-derived eicosanoids were reduced by 35% to 83%. The changes were not linear, with the largest changes in eicosanoids observed with the lower doses. A mathematical model predicts colonic tissue eicosanoids from the EPA:AA ratio in serum and the EPA dose. Every 10% increase in serum EPA:AA was associated with a 2% decrease in the (geometric) mean of PGE2 in the distal colon. These mathematical relationships can now be applied to individualized EPA dosing in clinical trials. PMID- 25139295 TI - Widefield optical imaging of changes in uptake of glucose and tissue extracellular pH in head and neck cancer. AB - The overall objective of this study was to develop an optical imaging approach to simultaneously measure altered cell metabolism and changes in tissue extracellular pH with the progression of cancer using clinically isolated biopsies. In this study, 19 pairs of clinically normal and abnormal biopsies were obtained from consenting patients with head and neck cancer at University of California, Davis Medical Center. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4 yl)amino]-2-deoxy-D-glucose) and Alexa 647-pHLIP [pH (low) insertion peptide] was measured noninvasively by widefield imaging, and correlated with pathologic diagnosis. The results of widefield imaging of clinical biopsies demonstrated that 2-NBDG and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. The results also demonstrated the potential of this approach to detect subepithelial lesions. Topical application of the contrast agents generated a significant increase in fluorescence contrast (3- to 4-fold) in the cancer biopsies as compared with the normal biopsies, irrespective of the patient and location of the biopsy within a head and neck cavity. This unpaired comparison across all the patients with cancer in this study highlights the specificity of the imaging approach. Furthermore, the results of this study indicated that changes in intracellular glucose metabolism and cancer acidosis are initiated in the early stages of cancer, and these changes are correlated with the progression of the disease. In conclusion, this novel optical molecular imaging approach to measure multiple biomarkers in cancer has a significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia. PMID- 25139296 TI - Analysis of DNA methylation in bowel lavage fluid for detection of colorectal cancer. AB - Aberrant DNA methylation could potentially serve as a biomarker for colorectal neoplasms. In this study, we assessed the feasibility of using DNA methylation detected in bowel lavage fluid (BLF) for colorectal cancer screening. A total of 508 BLF specimens were collected from patients with colorectal cancer (n = 56), advanced adenoma (n = 53), minor polyp (n = 209), and healthy individuals (n = 190) undergoing colonoscopy. Methylation of 15 genes (miR-1-1, miR-9-1, miR-9-3, miR-34b/c, miR-124-1, miR-124-2, miR-124-3, miR-137, SFRP1, SFRP2, APC, DKK2, WIF1, LOC386758, and ZNF582) was then analyzed in MethyLight assays, after which receiver operating characteristic (ROC) curves were analyzed to assess the diagnostic performance of BLF methylation. Through analyzing BLF specimens in a training set (n = 345), we selected the three genes showing the greatest sensitivity for colorectal cancer detection (miR-124-3, 71.8%; LOC386758, 79.5%; and SFRP1, 74.4%). A scoring system based on the methylation of those three genes (M-score) achieved 82% sensitivity and 79% specificity, and the area under the ROC curve (AUC) was 0.834. The strong performance of this system was then validated in an independent test set (n = 153; AUC = 0.808). No significant correlation was found between M-score and the clinicopathologic features of the colorectal cancers. Our results demonstrate that DNA methylation in BLF specimens may be a useful biomarker for the detection of colorectal cancer. PMID- 25139297 TI - Comparative analysis of gender-related differences in symptoms and referral patterns prior to initial diagnosis of urothelial carcinoma of the bladder: a prospective cohort study. AB - OBJECTIVE: To analyze gender-specific differences regarding clinical symptoms, referral patterns and tumor biology prior to initial diagnosis of urothelial carcinoma of the bladder (UCB). METHODS: A consecutive series of patients with an initial diagnosis of UCB was included. All patients completed a questionnaire on demographics, clinical symptoms and referral patterns. RESULTS: In total, 68 patients (50 men, 18 women) with newly diagnosed UCB at admission for transurethral resection of bladder tumors were recruited. Dysuria was more often observed in women (55.6 vs. 38.0%, p = 0.001). Direct consultation of the urologist was conducted by 84.0% of males and 66.7% of females (p = 0.120). One third of the women saw their general practitioner and/or gynecologist once or twice (p = 0.120) before referral to the urologist. Furthermore, women were significantly more often treated for urinary tract infections than men (61.1 vs. 20.0%, p = 0.005). Cystoscopy at first presentation to the urologist was more often performed in men than women (88.0 vs. 66.7%, p = 0.068), with a more favorable tumor detection rate at first cystoscopy in men (96.0 vs. 50.0%, p < 0.001). CONCLUSIONS: Delayed referral patterns might lead to deferred diagnosis of UCB and consequently to adverse outcome. Thus, primary care physicians might consider referring patients with bladder complaints to specialized care earlier. PMID- 25139298 TI - Preoperative smoking cessation can reduce postoperative complications in gastric cancer surgery. AB - BACKGROUND: Despite the close link between cigarette smoking and the development of gastric cancer, little is known about the effects of cigarette smoking on surgical outcomes after gastric cancer surgery. The aim of this study was to investigate whether preoperative smoking status and the duration of smoking cessation were associated with short-term surgical consequences in gastric cancer surgery. METHODS: Among 1,489 consecutive patients, 1,335 patients who underwent curative radical gastrectomy at the Samsung Medical Center between January and December 2009 were included in the present study. The smoking status was determined using questionnaires before surgery. Smokers were divided into four groups according to the duration of smoking cessation preoperatively (<2, 2-4, 4 8, and >8 weeks). The primary endpoint was postoperative complications (wound, lung, leakage, and bleeding); secondary endpoints were 3-year recurrence-free survival (RFS) and overall survival (OS). RESULTS: Five hundred twenty-two patients (39.1 %) were smokers. Smokers had a significantly higher overall incidence of postoperative complications than nonsmokers (12.3 vs. 5.2 %, P < 0.001, respectively), especially in impaired wound healing, pulmonary problems, and leakage. Smokers also had more severe complications than nonsmokers. After adjusting for other risk factors, the odds ratio (95 % CI) for the development of postoperative complications in the subgroups who stopped smoking <2 weeks, 2-4, 4 8, and >8 weeks preoperatively were 3.35 (1.92-5.83), 0.99 (0.22-4.38), 2.18 (1.00-4.76), and 1.32 (0.70-2.48), respectively, compared with the nonsmokers. There were no significant differences in 3-year RFS (P = 0.884) and OS (P = 0.258) between smokers and nonsmokers. CONCLUSIONS: Preoperative smoking cessation for at least 2 weeks will help to reduce the incidence of postoperative complications in gastric cancer surgery. PMID- 25139299 TI - Nursing assistants' communication styles in Korean American older adults with dementia: a review of the literature. AB - As ethnic diversity increases in the United States with the anticipated increase in dementia, it is critical to understand the implications of dementia and culturally appropriate communication for ethnic minority older adults with dementia. Utilizing the Ethno-Cultural Gerontological Nursing model and the Progressively Lowered Stress Threshold model, this article describes the relationship between nursing assistants' communication style and behavioral symptoms of dementia, focused on Korean American older adults with dementia residing in nursing homes. The discussion includes reviewing currently available studies, nursing implications, and suggestions for future studies. PMID- 25139301 TI - Monitoring of oil pollution at Gemsa Bay and bioremediation capacity of bacterial isolates with biosurfactants and nanoparticles. AB - Fifteen crude oil-degrading bacterial isolates were isolated from an oil-polluted area in Gemsa Bay, Red Sea, Egypt. Two bacterial species showed the highest growth rate on crude oil hydrocarbons. From an analysis of 16S rRNA sequences, these isolates were identified as Pseudomonas xanthomarina KMM 1447 and Pseudomonas stutzeri ATCC 17588. Gas Chromatographic (GC) analysis of the crude oil remaining in the culture medium after one week at 30 degrees C showed that the optimum biodegradation of crude petroleum oil was demonstrated at 50% in medium containing biosurfactant with two types of nanoparticles separately and two bacterial species. The complete degradation of some different members of polyaromatics and the percentage biodegradation of other polyaromatics increased in microcosm containing two different types of nanoparticles with biosurfactant after 7 days. In conclusion, these bacterial strains may be useful for the bioremediation process in the Gemsa Bay, Red Sea decreasing oil pollution in this marine ecosystem. PMID- 25139300 TI - Establishment of invasive and non-invasive reporter systems to investigate American elm-Ophiostoma novo-ulmi interactions. AB - Dutch elm disease (DED), caused by ascomycete fungi in the Ophiostoma genus, is the most devastating disease of American elm (Ulmus americana) trees. Cerato ulmin (CU), a hydrophobin secreted by the fungus, has been implicated in the development of DED, but its role in fungal pathogenicity and virulence remains uncertain and controversial. Here, we describe reporter systems based on the CU promoter and three reporter proteins (GFP, GUS and LUC), developed as research tools for quantitative and qualitative studies of DED in vitro, in vivo and in planta. A strain of the aggressive species Ophiostoma novo-ulmi was transformed with the reporter constructs using Agrobacterium-mediated transformation and the fungal transformants, namely M75-GFP, M75-GUS and M75-LUC, were examined for mitotic stability after repeated subcultures. The intensity of GFP fluorescence was strong in M75-GFP spores and hyphae, allowing microscopic investigations of spore structure, fungal morphogenesis and fungal development. The interaction of M75-GFP and U. americana callus cells was explored with scanning laser confocal microscopy facilitating qualitative studies on fungal strategies for the invasion and penetration of elm cells. M75-GUS was generated to provide an invasive, yet quantitative approach to study fungal-plant interactions in vitro and in planta. The generation of M75-LUC transformants was aimed at providing a non-destructive quantitative approach to study the role of CU in vivo. The sensitivity, low background signal and linearity of LUC assays all predict a very reliable approach to investigate and re-test previously claimed roles of this CU in fungal pathogenicity. These reporter systems provide new tools to investigate plant pathogen interactions in this complex pathosystem and may aid in better understanding the development of DED. PMID- 25139302 TI - Use of indicator chemicals to characterize the plastic fragments ingested by Laysan albatross. AB - Laysan albatross (Phoebastria immutabilis) ingest plastic marine debris of a wide range of shape, sizes and sources. To better characterize this plastic and provide insights regarding its provenance and persistence in the environment, we developed a simple method to classify plastic fragments of unknown origin according to the resin codes used by the Society of Plastics Industry. Known plastics were analyzed by gas chromatography-mass spectroscopy (GC-MS) to identify indicator chemicals characteristic of each plastic resin. Application of this method to fragments of ingested plastic debris from boluses of Laysan albatross from Kure Atoll, Hawai'i, yielded proportions of 0.8% High Density Polyethylene, 6.8% Polystyrene, 8.5% Polyethylene Terephthalate, 20.5% Polyvinyl Chloride and 68.4% Polypropylene. Some fragments were composed of multiple resin types. These results suggest that infrequently recycled plastics are the dominant fragments ingested by albatross, and that these are the most prevalent and persistent resin types in the marine environment. PMID- 25139303 TI - Causes and risk factors for revision hip preservation surgery. AB - BACKGROUND: Identifying causes and risk factors for failure of hip preservation surgery is critical to properly address residual pathological abnormalities in the revision setting and improve outcomes in this subset of patients. PURPOSE: To identify the structural causes of failure in both open and arthroscopic hip preservation procedures and to identify demographic and radiographic risk factors that correlate with the need for revision surgery. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A single-center hip preservation registry was reviewed (N = 1898 procedures in 1600 patients) to identify 147 patients (n = 152 procedures) who had undergone previous pelvic surgery. Exclusion criteria included residual deformity from pediatric hip disease (n = 5 patients). Preoperative demographics, intraoperative findings, radiographic data, and clinical outcome scores were compared between cohorts with and without revision surgery in the registry. Postoperative, short-term patient-reported outcome scores for the revision cohort were described. RESULTS: The most common reason for revision was residual intra-articular femoroacetabular impingement (74.8%), followed by extra-articular impingement (9.5%). The majority of revision cases (78.9%) could be addressed with arthroscopic surgery, with the exception of extra articular impingement or residual acetabular dysplasia, which necessitated open approaches. Patients who underwent revision were more likely to be female, were younger in age, and had worse preoperative outcome scores than did those in the primary cohort. Abnormal femoral version and the presence of acetabular dysplasia were not significantly different between the revision and primary cohorts. Short term improvements in patient-reported outcome scores were found in the revision cohort at a mean of 15.0 months from the last revision surgery. CONCLUSION: Residual intra- and extra-articular impingement were the most common reasons for revision in this cohort. Patients who underwent revision tended to be younger in age, were female, and had worse preoperative hip functional outcomes than did those in the primary cohort. Abnormal femoral version or acetabular coverage was not increased in our revision cohort. PMID- 25139305 TI - Abstracts of the XXXIXth Sir Peter Freyer Memorial Lecture and Surgical Symposium, September 5-6, 2014, Galway, Ireland. PMID- 25139306 TI - Abstracts of the Joint Annual Scientific Meeting of the Irish Association of Vascular Surgeons and the Northern Ireland Vascular Society, May 2014. PMID- 25139304 TI - Pharmacologic cholinesterase inhibition improves survival in acetaminophen induced acute liver failure in the mouse. AB - BACKGROUND: Acetaminophen (APAP) is one of the most widely used analgesic and antipyretic pharmaceutical substances in the world and accounts for most cases of drug induced liver injury resulting in acute liver failure. Acute liver failure initiates a sterile inflammatory response with release of cytokines and innate immune cell infiltration in the liver. This study investigates, whether pharmacologic acetylcholinesterase inhibition with neostigmine diminishes liver damage in acute liver failure via the cholinergic anti-inflammatory pathway. METHODS: Acute liver failure was induced in BALB/c mice by a toxic dose of acetaminophen (APAP). Neostigmine and/or N-acetyl-cysteine (NAC) were applied therapeutically at set time points and the survival was investigated. Liver damage was assessed by serum parameters, histopathology and serum cytokine assays 12 h after initiation of acute liver failure. RESULTS: Serum parameters, histopathology and serum cytokine assays showed pronounced features of acute liver failure 12 h after application of acetaminophen (APAP). Neostigmine treatment led to significant reduction of serum liver enzymes (LDH (47,147 +/- 12,726 IU/l vs. 15,822 +/- 10,629 IU/l, p = 0.0014) and ALT (18,048 +/- 4,287 IU/l vs. 7,585 +/- 5,336 IU/l, p = 0.0013), APAP-alone-treated mice vs. APAP + neostigmine-treated mice), inflammatory cytokine levels (IL-1beta (147 +/- 19 vs. 110 +/- 25, p = 0.0138) and TNF-alpha (184 +/- 23 vs. 130 +/- 33, p = 0.0086), APAP-alone-treated mice vs. APAP + neostigmine-treated mice) and histopathological signs of damage.Animals treated with NAC in combination with the peripheral cholinesterase inhibitor neostigmine showed prolonged survival and improved outcome. CONCLUSIONS: Neostigmine is an acetylcholinesterase inhibitor that ameliorates the effects of APAP-induced acute liver failure in the mouse and therefore may provide new treatment options for affected patients. PMID- 25139307 TI - Factors associated with long diagnostic delay in celiac disease. AB - OBJECTIVE: Here, we investigated the factors associated with long diagnostic delay in celiac disease and the impact of the national Current Care Guidelines in reducing the delay. MATERIAL AND METHODS: This population-based study involved 825 adult celiac disease patients. The diagnosis was considered delayed when the interval between first symptoms and diagnosis was >10 years. The patients were asked about the duration and type of symptoms before diagnosis, time and site (tertiary, secondary, or primary care) of the diagnosis, family history of the disease, and presence of significant comorbidities. Analysis was performed by binary logistic regression. RESULTS: Altogether, 261 (32%) out of 825 participants reported a diagnostic delay of >10 years. Female gender, neurological or musculoskeletal disorders and presence of diarrhea, abdominal pain, and malabsorption were associated with prolonged delay. Male gender, diagnosis after the introduction of the first Current Care Guidelines in 1997, and being detected by serological screening, and family history of celiac disease were associated with a lower risk of delayed diagnosis. Factors not associated with the delay were site of diagnosis, age, and presence of dermatitis herpetiformis, type 1 diabetes, or thyroidal disease. CONCLUSION: The number of long diagnostic delays in celiac disease has decreased over the past decades. The shift of diagnostics from secondary and tertiary care to primary care has not been detrimental. National guidelines together with increased awareness and active screening in at-risk groups of celiac disease are important in these circumstances. PMID- 25139308 TI - When you smile, you become happy: evidence from resting state task-based fMRI. AB - Simulation studies on emotion have shown that facial actions can initiate and modulate particular emotions. However, the neural mechanisms of these initiating and modulating functions are unclear. In this study, we used resting-state functional magnetic resonance imaging (fMRI) and task-based fMRI to explore these processes by examining spontaneous cerebral activities and brain activations under two conditions: holding a pen using only the teeth (HPT: facilitating the muscles typically associated with smiling) and holding a pen using only the lips (HPL: inhibiting the muscles typically associated with smiling). The resting state fMRI results showed that compared with the HPL condition, significant increases in the amplitudes of low-frequency fluctuations were found in the right posterior cingulate gyrus [PCG; Brodmann area 31 (BA31)] and in the left middle frontal gyrus (MFG; BA9) in the HPT condition. These findings might be related to the initiation of positive emotions (PCG) and to the control and allocation of attention (MFG). The task-based fMRI results showed that the inferior parietal lobule, left supplementary motor area, superior parietal lobule, precuneus, and bilateral middle cingulum were active when facial manipulation influenced the recognition of emotional facial expressions. These results demonstrate that facial actions might not only initiate a particular emotion and draw attention, but also influence face-based emotion recognition. PMID- 25139309 TI - Combination of LED light and platelet-derived growth factor to accelerate dentoalveolar osteogenesis. AB - AIM: This study aimed to evaluate the adjunctive effect of LED light in platelet derived growth factor (PDGF)-aided dentoalveolar osteogenesis. MATERIAL AND METHODS: Full-thickness osseous wounds were created on rat maxillae and were either unfilled or filled with poly-(D,L-lactide) and poly-(D,L-lactide-co glycolide) microspheres encapsulating PDGF. Animals received daily 660 +/- 25 nm LED light irradiation at 0, 10 (LD), or 20 (HD) J/cm(2) , were killed at days 4 28 (n = 6/group/time) and evaluated by microcomputed tomography (micro-CT), histology, and the expressions of osteopontin and tartrate-resistant acid phosphatase (TRAP). RESULTS: Greater osteogenesis was noted in the PDGF-treated defects at day 14. Under the LED light irradiation, osteogenesis was significantly greater in both LD and HD groups of the non-PDGF-treated defects, but only in the LD group of the PDGF-treated defects. No significant differences in osteogenesis among groups were noted at day 28. Greater bone marrow space was noted in the LED light-irradiated specimens, especially in the PDGF-treated defects at both time points. Osteopontin was significantly promoted in the LD group at both time points, and TRAP was significantly promoted in all LED light irradiated groups at day 28. CONCLUSION: LED light could an adjunct to promote early PDGF-aided dentoalveolar osteogenesis by facilitating the osteoblast osteoclast coupling. PMID- 25139311 TI - Abstracts of the Joint meeting of the Federation of European Physiological Societies (FEPS) and the Hungarian Physiological Society, 27-30 August 2014, Budapest, Hungary. PMID- 25139310 TI - Transcriptional responses of the bacterial antagonist Serratia plymuthica to the fungal phytopathogen Rhizoctonia solani. AB - Rhizobacteria with biocontrol ability exploit a range of mechanisms to compete successfully with other microorganisms and to ensure their growth and survival in the rhizosphere, ultimately promoting plant growth. The rhizobacterium Serratia plymuthica AS13 is able to promote oilseed rape growth and improve seedling survival in the presence of the fungal pathogen, Rhizoctonia solani AG 2-1; however, our understanding of the mechanisms underlying the antagonism of Serratia is limited. To elucidate possible mechanisms, genome-wide gene expression profiling of S. plymuthica AS13 was carried out in the presence or absence of R. solani. We used RNA sequencing methodology to obtain a comprehensive overview of Serratia gene expression in response to R. solani. The differential gene expression profiles of S. plymuthica AS13 revealed significantly increased expression of genes related to the biosynthesis of the antibiotic pyrrolnitrin (prnABCD), protease production and transporters. The results presented here provide evidence that antibiosis is a major functional mechanism underlying the antagonistic behaviour of S. plymuthica AS13. PMID- 25139312 TI - Canine progenitor epidermal keratinocytes express various inflammatory markers, including interleukin-8 and CD40, which are affected by certain antibiotics. AB - BACKGROUND: Bacterial skin infections are common in dogs and humans. Keratinocytes have phenotypic features of nonprofessional antigen-presenting cells and express various cytokines. However, little is known about the effects of antibiotics on inflammatory markers in canine keratinocytes. HYPOTHESIS/OBJECTIVES: To investigate inflammatory markers in canine progenitor epidermal keratinocytes (CPEKs) and to determine the effects of selected antibiotics on these markers. METHODS: The CPEKs were exposed for 2-24 h to three concentrations of amoxicillin, cefalexin, sulfadimethoxine, sulfamethoxazole (or its nitroso metabolite), amikacin or enrofloxacin. Enzyme-linked immunosorbent assay (ELISA) and immunocytochemistry were used to detect major histocompatibility complex (MHC) II. CD40 and CXCR1 [interleukin (IL)-8 receptor] were detected using ELISA. Secreted cytokines/chemokines were quantified using a multiplex kit. RESULTS: No MHC II protein was detected. CD40 protein was found at 24 h, with levels being significantly increased by enrofloxacin. The CPEKs secreted no detectable monocyte chemotactic protein-1; undetectable to low (picogram per millilitre range) concentrations of IL-6, IL-7, IL-10, IL-15, tumour necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony stimulating factor; and high (nanogram per millilitre range) concentrations of IL 8. Levels of IL-8 increased over 24 h following cell proliferation. They were significantly increased by enrofloxacin after 8 h, and by cefalexin, sulfadimethoxine, sulfamethoxazole, its nitroso metabolite and enrofloxacin after 24 h. The CPEKs expressed CXCR1. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine progenitor epidermal keratinocytes express various inflammatory proteins, with expression profiles being affected by certain antibiotics. This supports previous work showing keratinocytes to be mediators of inflammation and demonstrates the potential pro-inflammatory effects of certain antibiotics in the skin. PMID- 25139313 TI - Update on ultra-long-acting beta agonists in chronic obstructive pulmonary disease. AB - INTRODUCTION: For the last two decades, long-acting beta agonists (LABAs) have been a cornerstone in the management of chronic obstructive pulmonary disease (COPD). They relax airway smooth muscle and augment expiratory airflow, which reduces hyperinflation and improves dyspnea, functional capacity and quality of life. In recent years, Indacaterol, a LABA with an ultra-long duration of action (ultra-LABA), which only requires once-daily dosing, was approved by the FDA. The clinical efficacy of indacaterol is comparable, and, in some aspects better, than the currently available LABAs. AREAS COVERED: This article reviews the pharmacological properties, clinical efficacy, safety and potential role of the ultra-LABAs in COPD management. EXPERT OPINION: Ultra-LABAs are effective bronchodilators with a prolonged duration of action. By decreasing dosing frequency, ultra-LABAs potentially may improve respiratory medication adherence, which is associated with better survival and less healthcare utilization. In addition to their salubrious benefits, beta agonists may produce untoward effects. Increased mortality and hospitalizations among patients with left ventricular heart failure, who were treated with beta agonists, has caused concern about their use in patients with COPD and heart disease. Further experience and testing will determine the optimal role of ultra-LABAs in the management of COPD. PMID- 25139314 TI - Disseminated intravascular coagulation secondary to advanced pancreatic cancer treated successfully with combination chemotherapy. AB - Both solid and hematologic malignancies may be complicated by coagulopathies. Disseminated intravascular coagulation (DIC) in the presence of pancreatic cancer is generally unrecognized and may have fatal consequences. The diagnosis of DIC in a patient with advanced cancer is a poor prognostic indicator. Presented here is a case study consisting of two patients presenting with a new diagnosis of pancreatic cancer complicated by DIC. Aggressive supportive treatment in addition to systemic chemotherapy consisting of gemcitabine and nab-paclitaxel was initiated and DIC was controlled. An early diagnosis of DIC and the administration of systemic chemotherapy with a high response rate and an ability to reduce tumor bulk rapidly may offer some patients the probability of recovery. PMID- 25139315 TI - Emotion regulation and the temporal dynamics of emotions: Effects of cognitive reappraisal and expressive suppression on emotional inertia. AB - The tendency for emotions to be predictable over time, labelled emotional inertia, has been linked to low well-being and is thought to reflect impaired emotion regulation. However, almost no studies have examined how emotion regulation relates to emotional inertia. We examined the effects of cognitive reappraisal and expressive suppression on the inertia of behavioural, subjective and physiological measures of emotion. In Study 1 (N = 111), trait suppression was associated with higher inertia of negative behaviours. We replicated this finding experimentally in Study 2 (N = 186). Furthermore, in Study 2, instructed suppressors and reappraisers both showed higher inertia of positive behaviours, and reappraisers displayed higher inertia of heart rate. Neither suppression nor reappraisal were associated with the inertia of subjective feelings in either study. Thus, the effects of suppression and reappraisal on the temporal dynamics of emotions depend on the valence and emotional response component in question. PMID- 25139316 TI - The intramuscular glucagon stimulation test does not provide good discrimination between normal and inadequate ACTH reserve when used in the investigation of short healthy children. AB - BACKGROUND/AIMS: Few studies have addressed the role of the glucagon stimulation test (GST) in evaluating the hypothalamic-pituitary-adrenal axis in children. We investigated the diagnostic value of the GST in evaluating the adrenocortical response in short healthy children. METHODS: The GST was performed in 190 children investigated for short stature. A peak cortisol >500 nmol/l was considered a normal response. In the 45 (23.7%) with subnormal response, a 250 MUg ACTH test was done. RESULTS: The rate of subnormal adrenal response to GST was higher among boys (33.9 vs. 8.9%, p < 0.001) and among children >=6 years than among younger children (32.7 vs. 18.4%, p < 0.02). Both mean basal and peak cortisol levels were higher in girls than in boys: 381 +/- 165 vs. 319 +/- 151 nmol/l (p = 0.003) and 741 +/- 102 vs. 595 +/- 208 nmol/l (p < 0.001), respectively. Peak cortisol on GST was associated with basal cortisol (r = 0.45, p < 0.001) but not with glucose nadir (r = -0.31, p = 0.67), peak GH (r = 0.069, p = 0.33) or BMI-SDS (r = -0.08, p = 0.28). Peak cortisol was >500 nmol/l in all the patients undergoing an ACTH stimulation test. CONCLUSIONS: Since adrenal response to GST is age- and gender-related and the false-positive rate is high, its routine performance in healthy children warrants reconsideration. PMID- 25139317 TI - Transdermal uptake and organ distribution of silver from two different wound dressings in rats after a burn trauma. AB - Silver-containing wound dressings are an integral part of wound therapy in adult and pediatric burn patients. The antimicrobial effect of silver is well known and has been described in numerous studies. Side effects are rarely reported from silver-containing wound care products, even though systemic absorption of silver has been shown by elevated levels of silver in the blood of patients after silver exposure during wound therapy. This animal study investigated the silver levels of blood and in which organs and tissues silver is detectable after long-term application of silver-containing wound dressings after a burn trauma. In male rats, a major full-thickness scald was created on their backs according to a standardized burn model. Two different silver-containing wound dressings (nanocrystalline silver [NCS] and silver sulphate foam [SSF]) were applied initially and changed every 7 days. Weekly blood drawings revealed an increase of blood silver in week three with significant higher values in the SSF compared with NCS group (Ag MUg/kg 135.8 vs. 61.7; means; p <= 0.05). Thereafter, the NCS group showed significantly higher blood silver levels than the SSF group at week five (Ag MUg/kg 192.3 vs. 81.3; means; p <= 0.01) and six (Ag MUg/kg 168.2 vs. 32.9; means; p <= 0.01). After 6 weeks, the animals were sacrificed, and the organs and tissues were analyzed for their silver content by inductively coupled plasma mass-spectrometry. Silver was detectable in all analyzed organs and tissue samples, with higher silver values in parenchymatous organs in the NCS than SSF group (Ag MUg/kg; spleen: 3,469 vs. 260; kidney: 3,186 vs. 289; liver: 2,022 vs. 313; means; p <= 0.05). Silver was also detectable in brain, testis, lung, heart, and muscle tissue. PMID- 25139319 TI - A family cluster of negative T-waves reversible after hyperventilation in young brothers without epicardial coronary disease. PMID- 25139318 TI - Acquired von Willebrand syndrome in adult patients with congenital heart disease. AB - OBJECTIVES: Postoperative bleeding is common in patients with congenital heart disease (CHD). However, little is known about the role and prevalence of acquired von Willebrand syndrome (AVWS). METHODS: We evaluated the prevalence of AVWS in relation to underlying cardiac defects, operative procedures and the presence of Eisenmenger syndrome. The prothrombin time, aPTT, platelet function analysis (PFA 100), von Willebrand factor antigen (VWF:Ag), VWF activity, VWF collagen binding activity (VWF:CB), factor VIII activity and multimeric analysis were measured in addition to tests evaluating heart, liver and kidney functions. RESULTS: A total of 221 patients were screened and 192 patients were included in the study. The overall prevalence of AVWS was 20.8%. AVWS was identified across all of the cardiac defects, with the highest prevalence in the defects of great complexity (38.6% compared to 9.4% in patients with CHD of simple/moderate complexity, p<0.001), Eisenmenger syndrome (p<0.001) and more severe heart failure symptoms (NYHA III/IV vs. NYHA I, p<0.001; NYHA III/IV vs. NYHA II, p=0.044). A combination of multimeric analysis, VWF:CB to VWF:Ag ratio (sensitivity: 77.5%, specificity: 93.3%) and PFA-100 (PFA Col/Epi sens.: 77%, spec.: 52%; PFA Col/ADP sens.: 75%, spec.: 74.3%) were used to detect AVWS. CONCLUSIONS: This study demonstrated that AVWS occurred in patients with various congenital cardiac defects, but the highest prevalence occurred in the patients with complex CHD and Eisenmenger syndrome. We, therefore, suggest preoperative screening for AVWS in all of the patients with CHD, particularly in the patients with CHD of greater complexity and suffering from Eisenmenger syndrome. PMID- 25139320 TI - Life threatening iatrogenic abnormal venous return following atrial septal defect surgery. PMID- 25139322 TI - A safe and easy technique to sample the coronary sinus--facilitating a closer look at cardiac disease. PMID- 25139321 TI - Atorvastatin treatment improves the effects of mesenchymal stem cell transplantation on acute myocardial infarction: the role of the RhoA/ROCK/ERK pathway. AB - BACKGROUND: Statins protect mesenchymal stem cells (MSCs) against the harsh microenvironment and improve the efficacy of MSC transplantation after acute myocardial infarction (AMI); however, the mechanism remains uncertain. Furthermore, the transdifferentiation potential of MSCs in the post-infarct heart remains highly controversial. The RhoA/Rho-associated coiled-coil-forming kinase (ROCK) pathway participates in many aspects of the damaged heart after AMI and related to the "pleiotropic" effects of statins. This study aimed to explore whether atorvastatin (ATV) facilitates the survival and therapeutic efficacy of MSCs via the inhibition of RhoA/ROCK pathway and subsequently its downstream molecular extracellular regulated protein kinase (ERK1/2), and to investigate the transdifferentiation potential of MSCs in vivo. METHODS AND RESULTS: Female rats received myocardial injections of male rat MSCs 30 min after AMI. Four weeks after AMI, ATV combined with MSC treatment resulted in improved cardiac function and reduced infarct area. ATV facilitated the MSC survival, as revealed by the increased expression of Y chromosomal genes and the increased number of Y chromosome-positive cells; however, no transdifferentiation markers were observed. ATV inhibited the production of inflammatory cytokines both in vitro and vivo, accompanied by suppression of ROCK and ERK activities. Geranylgeranyl pyrophosphate (GGPP) abrogated the effects of ATV in the H9c2 cells under hypoxia/serum deprivation (H/SD), while the ROCK inhibitor fasudil mimicked the benefits of ATV after AMI. CONCLUSIONS: ATV improves the post-infarct microenvironment via RhoA/ROCK/ERK inhibition and thus facilitates the survival and efficacy of implanted MSCs. Transdifferentiation may be not responsible for the cardiac benefits that follow MSC transplantation. PMID- 25139323 TI - Residual platelet reactivity and outcomes with 5 mg prasugrel therapy in elderly patients undergoing percutaneous coronary intervention. AB - BACKGROUND: In acute coronary syndrome (ACS) patients older than 75 years old, prasugrel 10 mg maintenance therapy has shown less clinical efficacy and higher risk of bleeding. In patients older than 75 years, a prasugrel dose of 5 mg should be used if treatment is deemed necessary. OBJECTIVE: The aim of this study was to compare platelet reactivity and outcomes in elderly patients receiving prasugrel 5mg therapy with non-elderly patients receiving prasugrel 10 mg therapy. METHODS AND RESULTS: Consecutive ACS patients undergoing percutaneous coronary intervention (PCI) treated with prasugrel were included. Of 718 patients, 228 (32%) had >=75 years and received prasugrel 5 mg/day. Residual platelet reactivity (RPR) was 47+/-18% and 36+/-16% in the elderly and non elderly group, respectively (p=0.001). High RPR (>=70%) was found in 9% and 2% (p=0.0001) in elderly and non-elderly patients, respectively. In the 6-month follow-up, there was no difference in mortality, stent thrombosis, and reinfarction rates between the 2 groups but a higher rate of TIMI minor bleeding (7.9% vs 2.4%; p=0.001) in elderly as compared with younger patients. Age>=75 years was independently associated with bleeding events (HR 2.162 [1.105-4.229]; p=0.024). CONCLUSIONS: Elderly patients receiving prasugrel 5mg are more likely to experience high RPR than younger patients treated by prasugrel 10 mg. Despite the use of a reduced prasugrel maintenance dose and a higher level of RPR, elderly patients show increased risk of bleeding during prasugrel therapy as compared to younger patients. PMID- 25139324 TI - Comparative evaluation of HAS-BLED and ATRIA scores by investigating the full potential of their bleeding prediction schemes in non-valvular atrial fibrillation patients on vitamin-K antagonists. PMID- 25139325 TI - Experimental assessment of the effects of sublethal salinities on growth performance and stress in cultured tra catfish (Pangasianodon hypophthalmus). AB - The effects of a range of different sublethal salinities were assessed on physiological processes and growth performance in the freshwater 'tra' catfish (Pangasianodon hypophthalmus) juveniles over an 8-week experiment. Fish were distributed randomly among 6 salinity treatments [2, 6, 10, 14 and 18 g/L of salinity and a control (0 g/L)] with a subsequent 13-day period of acclimation. Low salinity conditions from 2 to 10 g/L provided optimal conditions with high survival and good growth performance, while 0 g/L and salinities >14 g/L gave poorer survival rates (p < 0.05). Salinity levels from freshwater to 10 g/L did not have any negative effects on fish weight gain, daily weight gain, or specific growth rate. Food conversion ratio, however, was lowest in the control treatment (p < 0.05) and highest at the maximum salinities tested (18 g/L treatment). Cortisol levels were elevated in the 14 and 18 g/L treatments after 6 h and reached a peak after 24-h exposure, and this also led to increases in plasma glucose concentration. After 14 days, surviving fish in all treatments appeared to have acclimated to their respective conditions with cortisol levels remaining under 5 ng/mL with glucose concentrations stable. Tra catfish do not appear to be efficient osmoregulators when salinity levels exceed 10 g/L, and at raised salinity levels, growth performance is compromised. In general, results of this study confirm that providing culture environments in the Mekong River Basin do not exceed 10 g/L salinity and that cultured tra catfish can continue to perform well. PMID- 25139326 TI - 2-Phenylethynesulfonamide (PES) uncovers a necrotic process regulated by oxidative stress and p53. AB - 2-Phenylethynesulfonamide (PES) or pifithrin-MU is a promising anticancer agent with preferential toxicity for cancer cells. The type of cell death and the molecular cascades activated by this compound are controversial. Here, we demonstrate PES elicits a caspase- and BAX/BAK-independent non-necroptotic necrotic cell death, since it is not inhibited by necrostatin-1. This process is characterized by an early generation of reactive oxygen species (ROS) resulting in p53 up-regulation. Accordingly, thiolic antioxidants protect cells from PES induced death. Furthermore, inhibiting the natural sources of glutathione with l buthionine-sulfoximine (BSO) strongly cooperates with PES in triggering cytotoxicity. Genetically modified p53-null or p53 knocked-down cells show resistance to PES-driven necrosis. The predominant localization of p53 in chromatin-enriched fractions added to the up-regulation of the p53-responsive gene p21, strongly suggest the involvement of a transcription-dependent p53 program. On the other hand, we report an augmented production of ROS in p53 positive cells that, added to the increased p53 content in response to PES elicited ROS, suggests that p53 and ROS are mutually regulated in response to PES. In sum, p53 up-regulation by ROS triggers a positive feedback loop responsible of further increasing ROS production and reinforcing PES-driven non necroptotic necrosis. PMID- 25139331 TI - Neurocognitive predictors of substance use disorders and nicotine dependence in ADHD probands, their unaffected siblings, and controls: a 4-year prospective follow-up. AB - BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a risk factor for substance use disorders (SUDs) and nicotine dependence (ND). Neurocognitive deficits may predict the increased risk of developing SUDs and nicotine dependence. METHODS: This study comprised three groups derived from the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study: ADHD probands (n = 294), unaffected siblings (n = 161), and controls (n = 214). At baseline (age = 12.2), a range of neurocognitive functions was assessed including executive functions (inhibition, working memory, timing), measures of motor functioning (motor timing and tracking) and IQ. After a mean follow-up of 4.2 years, SUDs and ND were assessed. RESULTS: None of the neurocognitive functions predicted later SUDs or ND in ADHD probands, even after controlling for medication use and conduct disorder. Slower response inhibition predicted later nicotine dependence in unaffected siblings (OR = 2.06, 95% CI = 1.22-3.48), and lower IQ predicted increased risk for SUDs in controls (OR = 1.96, 95% CI = 1.12 3.44). CONCLUSIONS: Cold executive functions, motor functioning, and IQ did not predict the elevated risk of SUDs and ND in ADHD. Future studies should target 'hot' executive functions such as reward processing as risk factors for SUDs or ND. PMID- 25139327 TI - Modulating energy arriving at photochemical reaction centers: orange carotenoid protein-related photoprotection and state transitions. AB - Photosynthetic organisms tightly regulate the energy arriving to the reaction centers in order to avoid photodamage or imbalance between the photosystems. To this purpose, cyanobacteria have developed mechanisms involving relatively rapid (seconds to minutes) changes in the photosynthetic apparatus. In this review, two of these processes will be described: orange carotenoid protein(OCP)-related photoprotection and state transitions which optimize energy distribution between the two photosystems. The photoactive OCP is a light intensity sensor and an energy dissipater. Photoactivation depends on light intensity and only the red active OCP form, by interacting with phycobilisome cores, increases thermal energy dissipation at the level of the antenna. A second protein, the "fluorescence recovery protein", is needed to recover full antenna capacity under low light conditions. This protein accelerates OCP conversion to the inactive orange form and plays a role in dislodging the red OCP protein from the phycobilisome. The mechanism of state transitions is still controversial. Changes in the redox state of the plastoquinone pool induce movement of phycobilisomes and/or photosystems leading to redistribution of energy absorbed by phycobilisomes between PSII and PSI and/or to changes in excitation energy spillover between photosystems. The different steps going from the induction of redox changes to movement of phycobilisomes or photosystems remain to be elucidated. PMID- 25139332 TI - Lack of association between the 389C>T polymorphism (rs769217) in the catalase (CAT) gene and the risk of vitiligo: an update by meta-analysis. AB - BACKGROUND/OBJECTIVES: The catalase (CAT) T/C at codon 389 in the exon 9 polymorphism has been implicated in susceptibility to vitiligo but a large number of studies have reported inconclusive results. The purpose of this study is to evaluate the association between the catalase gene polymorphism (389C>T) and the risk of vitiligo. METHODS: A meta-analysis was carried out to analyse the association between 389C>T and vitiligo risk. RESULTS: Eight case-control studies with 2923 cases and 4237 controls were included in the meta-analysis. The results indicated that there was no association between this polymorphism and vitiligo (TT + CT versus CC: OR = 1.08, 95% CI = 0.98-1.20, P = 0.11, T versus C: OR = 1.07, 95% CI = 0.99-1.16, P = 0.092). In a subgroup analysis by ethnicity, no significant association between the CAT gene 389C>T polymorphism and vitiligo susceptibility was found in Caucasians (TT + CT versus CC: OR = 1.15, 95% CI = 0.98-1.35, P = 0.08; T versus C: OR = 1.07, 95% CI = 0.97-1.19, P = 0.173) and Asians (TT + CT versus CC: OR = 1.12, 95% CI =0.93-1.34, P = 0.23; T versus C: OR = 1.07, 95% CI = 0.94-1.21, P = 0.321). CONCLUSIONS: Our results suggest that 389C>T may not contribute to vitiligo susceptibility. However, larger primary studies with the consideration of gene-environment and gene-gene interactions are still required to further evaluate the interaction of CAT gene polymorphism with vitiligo susceptibility. PMID- 25139333 TI - Diagnostic and prognostic value of preoperative combined GFAP, IGFBP-2, and YKL 40 plasma levels in patients with glioblastoma. AB - BACKGROUND: Circulating proteins released by tumor cells have recently been investigated as potential single surrogate biomarkers for glioblastoma multiforme (GBM). The aim of the current hypothesis-generating study was to evaluate the diagnostic and prognostic role of preoperative insulin-like growth factor-binding protein 2 (IGFBP-2), chitinase-3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) plasma levels in patients with GBM, both as single markers and as a combined profile. METHODS: Plasma samples from 111 patients with GBM and a subset of 40 patients with nonglial brain tumors were obtained preoperatively. Plasma from 99 healthy controls was also analyzed. IGFBP-2, YKL-40, and GFAP levels were determined using enzyme-linked immunoadsorbent assay tests. Their association with histological and radiological variables was assessed. RESULTS: Circulating levels of all 3 proteins were found to be significantly higher in patients with GBM compared with healthy controls (P < .01). Only YKL-40 and GFAP were found to demonstrate significant differences between patients with GBM and nonglial brain tumors (P = .04). GFAP was undetectable (<0.02 ng/mL) in all patients without GBM. A receiver operating characteristic analysis accounting for a 2-step diagnostic procedure including the 3 biomarkers afforded an area under the curve of 0.77 for differentiating patients with GBM from those with nonglial brain tumors. There was a significant correlation between tumor volume and plasma IGFBP-2 level (Spearman Rho correlation coefficient, 0.22; P = .025) and GFAP (Spearman Rho correlation coefficient, 0.36; P < .001) among patients with GBM. Preoperative plasma IGFBP-2 levels were found to be independently associated with worse overall survival among patients with GBM (hazard ratio, 1.3; P = .05). CONCLUSIONS: A combined profile of preoperative IGFBP-2, GFAP, and YKL-40 plasma levels could serve as an additional diagnostic tool for patients with inoperable brain lesions suggestive of GBM. In addition, IGFBP-2 levels appear to constitute an independent prognostic factor in patients with GBM. PMID- 25139334 TI - Modeling and forecasting the distribution of Vibrio vulnificus in Chesapeake Bay. AB - AIM: To construct statistical models to predict the presence, abundance and potential virulence of Vibrio vulnificus in surface waters of Chesapeake Bay for implementation in ecological forecasting systems. METHODS AND RESULTS: We evaluated and applied previously published qPCR assays to water samples (n = 1636) collected from Chesapeake Bay from 2007-2010 in conjunction with State water quality monitoring programmes. A variety of statistical techniques were used in concert to identify water quality parameters associated with V. vulnificus presence, abundance and virulence markers in the interest of developing strong predictive models for use in regional oceanographic modeling systems. A suite of models are provided to represent the best model fit and alternatives using environmental variables that allow them to be put to immediate use in current ecological forecasting efforts. CONCLUSIONS: Environmental parameters such as temperature, salinity and turbidity are capable of accurately predicting abundance and distribution of V. vulnificus in Chesapeake Bay. Forcing these empirical models with output from ocean modeling systems allows for spatially explicit forecasts for up to 48 h in the future. SIGNIFICANCE AND IMPACT OF THE STUDY: This study uses one of the largest data sets compiled to model Vibrio in an estuary, enhances our understanding of environmental correlates with abundance, distribution and presence of potentially virulent strains and offers a method to forecast these pathogens that may be replicated in other regions. PMID- 25139335 TI - The difference in immune response and IL-12p35 methylation between newborns and adults. AB - BACKGROUND: The immune system of newborn is generally depressed by impaired production of Th1-cell associated cytokines, which results in increased susceptibility to intracellular pathogens and poor response to vaccinations. For avoiding abortion, the maternal and fetal immune systems tend to Th2-cell polarizing cytokines. Besides, IL-12p35 is a determining factor of the bioactivity of IL-12, which has an important role in the Th1 response. Recently methylated DNA is known to associate to inhibit transcription. Therefore, we explored the methylation status of CpG sites upstream of the coding sequence of the IL-12p35 gene to determine whether neonatal peripheral blood mononuclear cell (PBMC) synthesis lower level of IL-12 is related to methylated DNA. RESULTS: PBMCs from adults expressed higher levels of IL-12p40 (p = 0.303) and IL-12p70 (p = 0.045) and had a strong ability to produce IL-12p35 mRNA (p = 0.01). However, there was no difference in the methylation status of CpG sites in the promoter of IL-12p35 between adults and newborns. CONCLUSIONS: We found that PBMC synthesis of bioactive IL-12p70 was significantly impaired in the neonatal period, potentially though a reduction in IL-12p35 production. The reeducation in IL 12p35 production might not be due to methylation of the promoter gene. But, the impairment of IL-12p35 expression during the neonatal period might be caused by other epigenetic regulation occurs in the chromatin level. PMID- 25139337 TI - Single-nucleotide polymorphism associations in common with immune responses to measles and rubella vaccines. AB - Single-nucleotide polymorphisms (SNPs) in candidate immune response genes were evaluated for associations with measles- and rubella-specific neutralizing antibodies, interferon (IFN)-gamma, and interleukin (IL)-6 secretion in two separate association analyses in a cohort of healthy immunized subjects. We identified six SNP associations shared between the measles-specific and rubella specific immune responses, specifically neutralizing antibody titers (DDX58), secreted IL-6 (IL10RB, IL12B), and secreted IFN-gamma (IFNAR2, TLR4). An intronic SNP (rs669260) in the antiviral innate immune receptor gene, DDX58, was significantly associated with increased neutralizing antibody titers for both measles and rubella viral antigens post-MMR vaccination (p values 0.02 and 0.0002, respectively). Significant associations were also found between IL10RB (rs2284552; measles study p value 0.006, rubella study p value 0.00008) and IL12B (rs2546893; measles study p value 0.005, rubella study p value 0.03) gene polymorphisms and variations in both measles- and rubella virus-specific IL-6 responses. We also identified associations between individual SNPs in the IFNAR2 and TLR4 genes that were associated with IFN-gamma secretion for both measles and rubella vaccine-specific immune responses. These results are the first to indicate that there are SNP associations in common across measles and rubella vaccine immune responses and that SNPs from multiple genes involved in innate and adaptive immune response regulation may contribute to the overall human antiviral response. PMID- 25139336 TI - KIR diversity in Maori and Polynesians: populations in which HLA-B is not a significant KIR ligand. AB - HLA class I molecules and killer cell immunoglobulin-like receptors (KIR) form a diverse system of ligands and receptors that individualize human immune systems in ways that improve the survival of individuals and populations. Human settlement of Oceania by island-hopping East and Southeast Asian migrants started ~3,500 years ago. Subsequently, New Zealand was reached ~750 years ago by ancestral Maori. To examine how this history impacted KIR and HLA diversity, and their functional interaction, we defined at high resolution the allelic and haplotype diversity of the 13 expressed KIR genes in 49 Maori and 34 Polynesians. Eighty KIR variants, including four 'new' alleles, were defined, as were 35 centromeric and 22 telomeric KIR region haplotypes, which combine to give >50 full-length KIR haplotypes. Two new and divergent variant KIR form part of a telomeric KIR haplotype, which appears derived from Papua New Guinea and was probably obtained by the Asian migrants en route to Polynesia. Maori and Polynesian KIR are very similar, but differ significantly from African, European, Japanese, and Amerindian KIR. Maori and Polynesians have high KIR haplotype diversity with corresponding allotype diversity being maintained throughout the KIR locus. Within the population, each individual has a unique combination of HLA class I and KIR. Characterizing Maori and Polynesians is a paucity of HLA-B allotypes recognized by KIR. Compensating for this deficiency are high frequencies (>50 %) of HLA-A allotypes recognized by KIR. These HLA-A allotypes are ones that modern humans likely acquired from archaic humans at a much earlier time. PMID- 25139338 TI - Smoking and risk of low- and high-grade prostate cancer: results from the REDUCE study. AB - PURPOSE: Although the relationship between smoking and prostate cancer risk is inconsistent, some studies show that smoking is associated with prostate cancer mortality. Whether this reflects delayed diagnosis or direct smoking-related effects is unknown. REDUCE, which followed biopsy-negative men with protocol dictated prostate-specific antigen (PSA)-independent biopsies at 2 and 4 years, provides an opportunity to evaluate smoking and prostate cancer diagnosis with minimal confounding from screening biases. EXPERIMENTAL DESIGN: Logistic regression was conducted to test the association between smoking and cancer on the first on-study biopsy (no cancer, low-grade Gleason 4-6, high-grade Gleason 7 10) in REDUCE. RESULTS: Of 6,240 men with complete data and >=1 on-study biopsy, 2,937 (45.8%) never smoked, 929 (14.5%) were current smokers, and 2,554 (39.8%) were former smokers. Among men with negative first on-study biopsies, smokers were 36% less likely to receive a second on-study biopsy (P < 0.001). At first on study biopsy, 941 (14.7%) men had cancer. Both current and former smoking were not significantly associated with either total or low-grade prostate cancer (all P > 0.36). Current (OR = 1.44, P = 0.028) but not former smokers (OR = 1.21, P = 0.12) were at increased risk of high-grade disease. On secondary analysis, there was an interaction between smoking and body mass index (BMI; Pinteraction = 0.017): current smokers with BMI <= 25 kg/m(2) had an increased risk of low-grade (OR = 1.54, P = 0.043) and high-grade disease (OR = 2.45, P = 0.002), with null associations for BMI >= 25 kg/m(2). CONCLUSION: Among men with elevated PSA and negative pre-study biopsy in REDUCE, in which biopsies were largely PSA independent, smoking was unrelated to overall prostate cancer diagnosis but was associated with increased risk of high-grade prostate cancer. PMID- 25139340 TI - Paracrine network: another step in the complexity of resistance to EGFR blockade? AB - Increased secretion of EGFR ligands amphiregulin and TGFalpha by limited KRAS mutant clones is suggested as a paracrine resistance mechanism to anti-EGFR antibodies in colorectal cancer models. These findings are biologically sound but need to be replicated, including in the clinical setting, to foresee whether they are clinically relevant and therapeutically exploitable. PMID- 25139339 TI - Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. AB - PURPOSE: To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAF(MT)) status in metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: A pooled analysis of four phase III studies in first-line treatment of mCRC (CAIRO, CAIRO2, COIN, and FOCUS) was performed. Primary outcome parameter was the hazard ratio (HR) for median progression-free survival (PFS) and overall survival (OS) in relation to MMR and BRAF. For the pooled analysis, Cox regression analysis was performed on individual patient data. RESULTS: The primary tumors of 3,063 patients were analyzed, of which 153 (5.0%) exhibited deficient MMR (dMMR) and 250 (8.2%) a BRAF(MT). BRAF(MT) was observed in 53 (34.6%) of patients with dMMR tumors compared with 197 (6.8%) of patients with proficient MMR (pMMR) tumors (P < 0.001). In the pooled dataset, median PFS and OS were significantly worse for patients with dMMR compared with pMMR tumors [HR, 1.33; 95% confidence interval (CI), 1.12-1.57 and HR, 1.35; 95% CI, 1.13-1.61, respectively), and for patients with BRAF(MT) compared with BRAF wild-type (BRAF(WT)) tumors (HR, 1.34; 95% CI, 1.17-1.54 and HR, 1.91; 95% CI, 1.66-2.19, respectively). PFS and OS were significantly decreased for patients with BRAF(MT) within the group of patients with pMMR, but not for BRAF status within dMMR, or MMR status within BRAF(WT) or BRAF(MT). CONCLUSIONS: Prevalence of dMMR and BRAF(MT) in patients with mCRC is low and both biomarkers confer an inferior prognosis. Our data suggest that the poor prognosis of dMMR is driven by the BRAF(MT) status. PMID- 25139343 TI - Ocular and histologic findings in a series of children with infantile pompe disease treated with enzyme replacement therapy. AB - PURPOSE: To report the ophthalmologic and histologic findings in a series of children with infantile Pompe disease treated with enzyme replacement therapy (ERT). METHODS: Records of children with infantile Pompe disease treated with ERT who had at least one complete ophthalmic examination and the ocular histopathology of children with infantile Pompe disease who were treated with ERT were reviewed. The patients' clinical history, including external ocular examination, ocular alignment and motility, dilated fundus examination, and cycloplegic refraction, was evaluated. A literature review was performed for ophthalmologic findings in infantile Pompe disease using PubMed. RESULTS: The clinical findings of 13 children were included and the ocular histopathology of 3 children with infantile Pompe disease who were treated with ERT were reviewed. Forty-six percent (6 of 13) had bilateral ptosis, 23% (3 of 13) had strabismus, 62% (8 of 13) had myopia, and 69% (9 of 13) had astigmatism. On histologic examination, there was vacuolar myopathy affecting the extraocular muscles, ciliary body, and iris smooth muscle and glycogen accumulation in corneal endothelial, lens epithelium, and retinal ganglion cells, and within lysosomes of scleral fibroblasts. CONCLUSIONS: It is important that ophthalmic providers are aware of the high prevalence of myopia, astigmatism, and ptosis in children with infantile Pompe disease treated with ERT because they are potentially amblyogenic but treatable factors. PMID- 25139344 TI - Endocrine effects of valproic acid therapy in girls with epilepsy: a prospective study. AB - BACKGROUND/AIM: It is controversial whether the endocrine dysfunction in epilepsy patients is caused by the epilepsy itself, the antiepileptic therapy, or both. We prospectively evaluated the long-term impact of valproic acid monotherapy compared to other anti-epileptic drugs on anthropometric, metabolic, hormonal, and ultrasonographic parameters in girls with epilepsy. METHODS: Fifty-seven female patients with epilepsy who had started therapy at mean age of 11.5 +/- 3.3 years, 42 with valproic acid (mean dose 13.1 +/- 7.0 mg/kg/day and 15 with other anti-epileptic agents were followed for a mean of 3.2 years (range 1.0-8.5 years) in our center. Clinical, hormonal and transabdominal pelvic ultrasound data were collected at 3 time points: before and 6-12 months after onset of anti-epileptic drug treatment; and at the last visit while patients were still taking anti epileptic drugs. RESULTS: There were no significant between-group differences regarding changes in height, body mass index standard deviation score, levels of glucose and insulin, or lipid and endocrine profile from first to last visits. Mean thyroid-stimulating hormone level increased significantly between first and last visit only in the valproic acid group (p < 0.001), with no significant difference in free T4 level over time or between groups. The rate of clinical polycystic ovary syndrome for the valproic acid group (11%) was comparable to that reported in healthy controls (5-10%). CONCLUSIONS: Administration of valproic acid had no adverse effect on body weight, metabolic status or endocrine function over an average follow-up of 3.2 years. Valproic acid appears to be safe for use in girls with epilepsy. PMID- 25139345 TI - Successful treatment of cataplexy in patients with early-infantile Niemann-Pick disease type C: use of tricyclic antidepressants. AB - Cataplexy is a brief episode of bilateral loss of muscle tone with intact consciousness, triggered by a variety of strong emotions such as anger, laugh, humor or surprise and it is considered to represent the physiologic atonia of rapid eye movement sleep. On the other hand, Niemann-Pick type C is a neurodegenerative lysosomal storage disease, characterized by the accumulation of cholesterol and glycosphingolipids. Cataplexy is a relatively specific and common neurologic sign seen in almost 50% of all patients with Niemann-Pick type C. The aim of this report is to demonstrate the successful treatment of cataplexy with the use of a tricyclic antidepressant imipiramine, in two patients between the ages 6-9, with mild to moderate mental retardation, molecularly diagnosed as Niemann-Pick type C 1 and currently under miglustat treatment and to discuss the possible mechanisms of drug action in the light of cataplexy and Niemann-Pick type C pathophysiology. PMID- 25139346 TI - The healthcare utilization and cost of treating patients experiencing inappropriate implantable cardioverter defibrillator shocks: a propensity score study. AB - BACKGROUND: Inappropriate shocks (IASs) from implantable cardioverter defibrillators (ICDs) are associated with decreased quality of life, but whether they increase healthcare utilization and treatment costs is unknown. We sought to determine the impact of IASs on subsequent healthcare utilization and treatment costs. METHODS: We conducted a case-control analysis of ICD patients at a single institution from 1997 to 2010 and who had >=12 months of post-ICD implant follow up. Cases included all patients experiencing an IAS during the first 12 months after implantation. Eligible control patients did not receive a shock of any kind during the 12 months after implantation. Propensity scores based on 36 covariates (area under curve = 0.78) were used to match cases to controls. We compared the rate (occurrences/person year [PY]) of healthcare utilization immediately following IAS to the end of the 12-month follow-up period to the rate in the no shock group over 12 months of follow-up. We also compared 12-month postimplant treatment (outpatient clinic, emergency room, and hospitalization) costs in both groups. RESULTS: A total of 76 patients experiencing >=1 IAS during the first 12 months after implant (contributing 48 PYs) were matched to 76 no-shock patients (contributing 76 PYs). Cardiovascular (CV)-related clinic visit and hospitalization rates were increased following an IAS compared to those not receiving a shock (4.0 vs 3.3 and 0.7 vs 0.5, respectively, P = 0.02 for both). CV-related emergency room visitation (0.15 vs 0.08) rates were also numerically higher following an IAS, but did not reach statistical significance (P = 0.26). Patients experiencing an IAS accrued greater treatment costs during the 12 months postimplant compared to no-shock patients ($13,973 +/- $46,345 vs $6,790 +/- $19,091, P = 0.001). CONCLUSION: Recipients of IAS utilize the healthcare system more frequently following an IAS than patients not experiencing a shock. This increased utilization results in higher costs of treating IAS patients during the 12 months postimplant. PMID- 25139347 TI - Balloon inflation time in angioplasty of dialysis access stenosis. PMID- 25139349 TI - Reed-Sternberg cell-derived lymphotoxin-alpha activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma. AB - It is known that cells within the inflammatory background in classical Hodgkin lymphoma (cHL) provide signals essential for the continual survival of the neoplastic Hodgkin and Reed-Sternberg (HRS) cells. However, the mechanisms underlying the recruitment of this inflammatory infiltrate into the involved lymph nodes are less well understood. In this study, we show in vitro that HRS cells secrete lymphotoxin-alpha (LTalpha) which acts on endothelial cells to upregulate the expression of adhesion molecules that are important for T cell recruitment. LTalpha also enhances the expression of hyaluronan which preferentially contributes to the recruitment of CD4(+) CD45RA(+) naive T cells under in vitro defined flow conditions. Enhanced expression of LTalpha in HRS cells and tissue stroma; and hyaluronan on endothelial cells are readily detected in involved lymph nodes from cHL patients. Our study also shows that although NF kappaB and AP-1 are involved, the cyclooxygenase (COX) pathway is the dominant regulator of LTalpha production in HRS cells. Using pharmacological inhibitors, our data suggest that activity of COX1, but not of COX2, directly regulates the expression of nuclear c-Fos in HRS cells. Our findings suggest that HRS cell derived LTalpha is an important mediator that contributes to T cell recruitment into lesional lymph nodes in cHL. PMID- 25139348 TI - Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton. AB - Following invasion of human red blood cells (RBCs) by the malaria parasite, Plasmodium falciparum, a remarkable process of remodeling occurs in the host cell mediated by trafficking of several hundred effector proteins to the RBC compartment. The exported virulence protein, P falciparum erythrocyte membrane protein 1 (PfEMP1), is responsible for cytoadherence of infected cells to host endothelial receptors. Maurer clefts are organelles essential for protein trafficking, sorting, and assembly of protein complexes. Here we demonstrate that disruption of PfEMP1 trafficking protein 1 (PfPTP1) function leads to severe alterations in the architecture of Maurer's clefts. Furthermore, 2 major surface antigen families, PfEMP1 and STEVOR, are no longer displayed on the host cell surface leading to ablation of cytoadherence to host receptors. PfPTP1 functions in a large complex of proteins and is required for linking of Maurer's clefts to the host actin cytoskeleton. PMID- 25139350 TI - X chromosome inactivation analysis reveals a difference in the biology of ET patients with JAK2 and CALR mutations. AB - Calreticulin mutations (CALR(MUT)) are found in a significant proportion of patients with essential thrombocythemia (ET) lacking JAK2(V617F) or MPL mutations. They are associated with substantially different hematological and clinical features and define a distinct subtype of ET. We show here that their presence is significantly correlated with a clonal X chromosome inactivation pattern (XCIP). Of 105 female ET patients investigated, 61 had an interpretable XCIP, and a clonal pattern was observed in 88% of CALR(MUT) patients compared with 26% of JAK2(V617F) (P = .0002) and 9% of JAK2(V617F)/MPL/CALR wild-type patients (P < .0001). Neutrophil CALR(MUT) level was significantly higher than JAK2(V617F) level (median, 50% vs 18%; P < .0001), and wild-type myelopoiesis was suppressed in CALR(MUT) but not JAK2(V617F) patients. These data are suggestive of truly monoclonal hematopoiesis in CALR(MUT) patients and provide further evidence that the biology associated with CALR mutations is markedly different from that of JAK2(V617F) mutations. PMID- 25139352 TI - Molecular and clinical predictors of inhibitor risk and its prevention and treatment in mild hemophilia A. AB - The risk for inhibitor development in mild hemophilia A (factor VIII levels between 5 and 40 U/dL) is larger than previously anticipated, continues throughout life, and is particularly associated with certain mutations in F8. Desmopressin may reduce inhibitor risk by avoiding exposure to FVIII concentrates, but the heterogenous biological response to desmopressin, showing large interindividual variation, may limit its clinical use. However, predictors of desmopressin response have been recently identified, allowing the selection of the best candidates to this treatment. PMID- 25139353 TI - Phosphoinositide 3-kinase beta mediates microvascular endothelial repair of thrombotic microangiopathy. AB - Thrombotic microangiopathy (TMA) commonly involves injury of kidney glomerular endothelial cells (ECs) and fibrin occlusion of the capillaries. The mechanisms underlying repair of the microvasculature and recovery of kidney function are poorly defined. In the developing vasculature, the phosphoinositide 3-kinase (PI3K) alpha isoform integrates many growth factor cues. However, the role of individual isoforms in repair of the established vasculature is unclear. We found that postnatal endothelial deletion of PI3Kbeta sensitizes mice to lethal acute kidney failure after TMA injury. In vitro, PI3Kbeta-deficient ECs show reduced angiogenic invasion of fibrin matrix with unaltered sensitivity to proapoptotic stress compared with wild-type ECs. This correlates with decreased expression of the EC tip cell markers apelin and Dll4 and is associated with a reduction in migration and proliferation. In vivo, PI3Kbeta-knockdown ECs are deficient in assembly of microvessel-like structures. These data identify a critical role for endothelial PI3Kbeta in microvascular repair following injury. PMID- 25139351 TI - Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts. AB - The bone marrow niche is thought to act as a permissive microenvironment required for emergence or progression of hematologic cancers. We hypothesized that osteoblasts, components of the niche involved in hematopoietic stem cell (HSC) function, influence the fate of leukemic blasts. We show that osteoblast numbers decrease by 55% in myelodysplasia and acute myeloid leukemia patients. Further, genetic depletion of osteoblasts in mouse models of acute leukemia increased circulating blasts and tumor engraftment in the marrow and spleen leading to higher tumor burden and shorter survival. Myelopoiesis increased and was coupled with a reduction in B lymphopoiesis and compromised erythropoiesis, suggesting that hematopoietic lineage/progression was altered. Treatment of mice with acute myeloid or lymphoblastic leukemia with a pharmacologic inhibitor of the synthesis of duodenal serotonin, a hormone suppressing osteoblast numbers, inhibited loss of osteoblasts. Maintenance of the osteoblast pool restored normal marrow function, reduced tumor burden, and prolonged survival. Leukemia prevention was attributable to maintenance of osteoblast numbers because inhibition of serotonin receptors alone in leukemic blasts did not affect leukemia progression. These results suggest that osteoblasts play a fundamental role in propagating leukemia in the marrow and may be a therapeutic target to induce hostility of the niche to leukemia blasts. PMID- 25139355 TI - Clonal analysis identifies hemogenic endothelium as the source of the blood endothelial common lineage in the mouse embryo. AB - The first blood and endothelial cells of amniote embryos appear in close association in the blood islands of the yolk sac (YS). This association and in vitro lineage analyses have suggested a common origin from mesodermal precursors called hemangioblasts, specified in the primitive streak during gastrulation. Fate mapping and chimera studies, however, failed to provide strong evidence for a common origin in the early mouse YS. Additional in vitro studies suggest instead that mesodermal precursors first generate hemogenic endothelium, which then generate blood cells in a linear sequence. We conducted an in vivo clonal analysis to determine the potential of individual cells in the mouse epiblast, primitive streak, and early YS. We found that early YS blood and endothelial lineages mostly derive from independent epiblast populations, specified before gastrulation. Additionally, a subpopulation of the YS endothelium has hemogenic activity and displays characteristics similar to those found later in the embryonic hemogenic endothelium. Our results show that the earliest blood and endothelial cell populations in the mouse embryo are specified independently, and that hemogenic endothelium first appears in the YS and produces blood precursors with markers related to definitive hematopoiesis. PMID- 25139354 TI - The DPY30 subunit in SET1/MLL complexes regulates the proliferation and differentiation of hematopoietic progenitor cells. AB - Epigenetic mechanisms, including histone modifications, have emerged as important factors influencing cell fate determination. The functional role of H3K4 methylation, however, remains largely unclear in the maintenance and differentiation of hematopoietic stem cells (HSCs)/hematopoietic progenitor cells (HPCs). Here we show that DPY30, a shared core subunit of the SET1/MLL family methyltransferase complexes and a facilitator of their H3K4 methylation activity, is important for ex vivo proliferation and differentiation of human CD34(+) HPCs. DPY30 promotes HPC proliferation by directly regulating the expression of genes critical for cell proliferation. Interestingly, while DPY30 knockdown in HPCs impaired their differentiation into the myelomonocytic lineage, it potently promoted hemoglobin production and affected the kinetics of their differentiation into the erythroid lineage. In an in vivo model, we show that morpholino-mediated dpy30 knockdown resulted in severe defects in the development of the zebrafish hematopoietic system, which could be partially rescued by coinjection of dpy30 messenger RNA. Taken together, our results establish a critical role of DPY30 in the proliferation and appropriate differentiation of hematopoietic progenitor cells and in animal hematopoiesis. Finally, we also demonstrate a crucial role of DPY30 in the growth of several MLL1-fusion-mediated leukemia cell lines. PMID- 25139356 TI - Somatic mutations identify a subgroup of aplastic anemia patients who progress to myelodysplastic syndrome. AB - The distinction between acquired aplastic anemia (AA) and hypocellular myelodysplastic syndrome (hMDS) is often difficult, especially nonsevere AA. We postulated that somatic mutations are present in a subset of AA, and predict malignant transformation. From our database, we identified 150 AA patients with no morphological evidence of MDS, who had stored bone marrow (BM) and constitutional DNA. We excluded Fanconi anemia, mutations of telomere maintenance, and a family history of BM failure (BMF) or cancer. The initial cohort of 57 patients was screened for 835 known genes associated with BMF and myeloid cancer; a second cohort of 93 patients was screened for mutations in ASXL1, DNMT3A, BCOR, TET2, and MPL. Somatic mutations were detected in 19% of AA, and included ASXL1 (n = 12), DNMT3A (n = 8) and BCOR (n = 6). Patients with somatic mutations had a longer disease duration (37 vs 8 months, P < .04), and shorter telomere lengths (median length, 0.9 vs 1.1, P < .001), compared with patients without mutations. Somatic mutations in AA patients with a disease duration of >6 months were associated with a 40% risk of transformation to MDS (P < .0002). Nearly one-fifth of AA patients harbor mutations in genes typically seen in myeloid malignancies that predicted for later transformation to MDS. PMID- 25139357 TI - A nonsense mutation in IKBKB causes combined immunodeficiency. AB - Identification of the molecular etiologies of primary immunodeficiencies has led to important insights into the development and function of the immune system. We report here the cause of combined immunodeficiency in 4 patients from 2 different consanguineous Qatari families with similar clinical and immunologic phenotypes. The patients presented at an early age with fungal, viral, and bacterial infections and hypogammaglobulinemia. Although their B- and T-cell numbers were normal, they had low regulatory T-cell and NK-cell numbers. Moreover, patients' T cells were mostly CD45RA(+)-naive cells and were defective in activation after T cell receptor stimulation. All patients contained the same homozygous nonsense mutation in IKBKB (R286X), revealed by whole-exome sequencing with undetectable IKKbeta and severely decreased NEMO proteins. Mutant IKKbeta(R286X) was unable to complex with IKKalpha/NEMO. Immortalized patient B cells displayed impaired IkappaBalpha phosphorylation and NFkappaB nuclear translocation. These data indicate that mutated IKBKB is the likely cause of immunodeficiency in these 4 patients. PMID- 25139358 TI - Donor CD4+ Foxp3+ regulatory T cells are necessary for posttransplantation cyclophosphamide-mediated protection against GVHD in mice. AB - Posttransplantation cyclophosphamide (PTCy) is an effective prophylaxis against graft-versus-host disease (GVHD). However, it is unknown whether PTCy works singularly by eliminating alloreactive T cells via DNA alkylation or also by restoring the conventional (Tcon)/regulatory (Treg) T-cell balance. We studied the role of Tregs in PTCy-mediated GVHD prophylaxis in murine models of allogeneic blood or marrow transplantation (alloBMT). In 2 distinct MHC-matched alloBMT models, infusing Treg-depleted allografts abrogated the GVHD-prophylactic activity of PTCy. Using allografts in which Foxp3(+) Tregs could be selectively depleted in vivo, either pre- or post-PTCy ablation of donor thymus-derived Tregs (tTregs) abolished PTCy protection against GVHD. PTCy treatment was associated with relative preservation of donor Tregs. Experiments using combinations of Foxp3(-) Tcons and Foxp3(+) Tregs sorted from different Foxp3 reporter mice indicated that donor Treg persistence after PTCy treatment was predominantly caused by survival of functional tTregs that retained Treg-specific demethylation and also induction of peripherally derived Tregs. Finally, adoptive transfer of tTregs retrieved from PTCy-treated chimeras rescued PTCy-treated, Treg-depleted recipients from lethal GVHD. Our findings indicate that PTCy-mediated protection against GVHD is not singularly dependent on depletion of donor alloreactive T cells but also requires rapidly recovering donor Tregs to initiate and maintain alloimmune regulation. PMID- 25139359 TI - Acute myocardial infarct size is related to periodontitis extent and severity. AB - Cardiovascular disease has been associated with 40% of deaths in high-income countries and 28% in lower-income countries. The relationship between periodontitis and acute myocardial infarction is well documented, but it has not been established whether the extent and severity of periodontitis influence the infarct size. This cross-sectional and analytic study was designed to investigate the association of chronic periodontitis extent and severity with acute myocardial infarct size as indicated by serum cardiac troponin I and myoglobin levels. Sociodemographic, periodontal, cardiologic, and hematologic variables were gathered in 112 consecutive patients with myocardial infarction. The extent (Arbes Index) and severity (Periodontal Inflammatory Severity Index) of the chronic periodontitis were significantly associated with troponin I levels after controlling for sociodemographic and clinical confounders (change in R (2) = .041, p < .02, and R (2) = .031, p = .04). However, only the extent index accounted for levels of myoglobin (change in R (2) = .030, p < .05), total leukocytes (change in R (2) = .041 p < .02), and neutrophils (change in R (2) = .059, p < .01). Mediated regression analysis showed that leukocytes and neutrophils may underlie these observed relationships of chronic periodontitis with troponin I and myoglobin. To our knowledge, this study contributes the first research data demonstrating that the extent and severity of periodontitis is positively associated with acute myocardial infarct size as measured by serum troponin I and myoglobin levels. PMID- 25139360 TI - In vivo bioreactors for mandibular reconstruction. AB - Large mandibular defects are difficult to reconstruct with good functional and aesthetic outcomes because of the complex geometry of craniofacial bone. While the current gold standard is free tissue flap transfer, this treatment is limited in fidelity by the shape of the harvested tissue and can result in significant donor site morbidity. To address these problems, in vivo bioreactors have been explored as an approach to generate autologous prefabricated tissue flaps. These bioreactors are implanted in an ectopic site in the body, where ossified tissue grows into the bioreactor in predefined geometries and local vessels are recruited to vascularize the developing construct. The prefabricated flap can then be harvested with vessels and transferred to a mandibular defect for optimal reconstruction. The objective of this review article is to introduce the concept of the in vivo bioreactor, describe important preclinical models in the field, summarize the human cases that have been reported through this strategy, and offer future directions for this exciting approach. PMID- 25139361 TI - Fluorapatite-modified scaffold on dental pulp stem cell mineralization. AB - In previous studies, fluorapatite (FA) crystal-coated surfaces have been shown to stimulate the differentiation and mineralization of human dental pulp stem cells (DPSCs) in two-dimensional cell culture. However, whether the FA surface can recapitulate these properties in three-dimensional culture is still unknown. This study examined the differences in behavior of human DPSCs cultured on electrospun polycaprolactone (PCL) NanoECM nanofibers with or without the FA crystals. Under near-physiologic conditions, the FA crystals were synthesized on the PCL nanofiber scaffolds. The FA crystals were evenly distributed on the scaffolds. DPSCs were cultured on the PCL+FA or the PCL scaffolds for up to 28 days. Scanning electron microscope images showed that DPSCs attached well to both scaffolds after the initial seeding. However, it appeared that more multicellular aggregates formed on the PCL+FA scaffolds. After 14 days, the cell proliferation on the PCL+FA was slower than that on the PCL-only scaffolds. Interestingly, even without any induction of mineralization, from day 7, the upregulation of several pro-osteogenic molecules (dmp1, dspp, runx2, ocn, spp1, col1a1) was detected in cells seeded on the PCL+FA scaffolds. A significant increase in alkaline phosphatase activity was also seen on FA-coated scaffolds compared with the PCL only scaffolds at days 14 and 21. At the protein level, osteocalcin expression was induced only in the DPSCs on the PCL+FA surfaces at day 21 and then significantly enhanced at day 28. A similar pattern was observed in those specimens stained with Alizarin red and Von Kossa after 21 and 28 days. These data suggest that the incorporation of FA crystals within the three-dimensional PCL nanofiber scaffolds provided a favorable extracellular matrix microenvironment for the growth, differentiation, and mineralization of human DPSCs. This FA-modified PCL nanofiber scaffold shows promising potential for future bone, dental, and orthopedic regenerative applications. PMID- 25139362 TI - Multiphasic scaffolds for periodontal tissue engineering. AB - For a successful clinical outcome, periodontal regeneration requires the coordinated response of multiple soft and hard tissues (periodontal ligament, gingiva, cementum, and bone) during the wound-healing process. Tissue-engineered constructs for regeneration of the periodontium must be of a complex 3 dimensional shape and adequate size and demonstrate biomechanical stability over time. A critical requirement is the ability to promote the formation of functional periodontal attachment between regenerated alveolar bone, and newly formed cementum on the root surface. This review outlines the current advances in multiphasic scaffold fabrication and how these scaffolds can be combined with cell- and growth factor-based approaches to form tissue-engineered constructs capable of recapitulating the complex temporal and spatial wound-healing events that will lead to predictable periodontal regeneration. This can be achieved through a variety of approaches, with promising strategies characterized by the use of scaffolds that can deliver and stabilize cells capable of cementogenesis onto the root surface, provide biomechanical cues that encourage perpendicular alignment of periodontal fibers to the root surface, and provide osteogenic cues and appropriate space to facilitate bone regeneration. Progress on the development of multiphasic constructs for periodontal tissue engineering is in the early stages of development, and these constructs need to be tested in large animal models and, ultimately, human clinical trials. PMID- 25139363 TI - Antibacterial efficacy of exogenous nitric oxide on periodontal pathogens. AB - Current treatments for periodontitis (e.g., scaling/root planing and chlorhexidine) have limited efficacy since they fail to suppress microbial biofilms satisfactorily over time, and the use of adjunctive antimicrobials can promote the emergence of antibiotic-resistant organisms. Herein, we report the novel application of nitric oxide (NO)-releasing scaffolds (i.e., dendrimers and silica particles) as anti-periodontopathogenic agents. The effectiveness of macromolecular NO release was demonstrated by a 3-log reduction in periodontopathogenic Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis viability. In contrast, Streptococcus mutans and Streptococcus sanguinis, caries-associated organisms, were substantially less sensitive to NO treatment. Both dendrimer- and silica-based NO release exhibited substantially less toxicity to human gingival fibroblasts at concentrations necessary to eradicate periodontopathogens than did clinical concentrations of chlorhexidine. These results suggest the potential utility of macromolecular NO-release scaffolds as a novel platform for the development of periodontal disease therapeutics. PMID- 25139364 TI - Advanced biomatrix designs for regenerative therapy of periodontal tissues. AB - Periodontitis is an inflammatory disease that causes loss of the tooth-supporting apparatus, including periodontal ligament, cementum, and alveolar bone. A broad range of treatment options is currently available to restore the structure and function of the periodontal tissues. A regenerative approach, among others, is now considered the most promising paradigm for this purpose, harnessing the unique properties of stem cells. How to make full use of the body's innate regenerative capacity is thus a key issue. While stem cells and bioactive factors are essential components in the regenerative processes, matrices play pivotal roles in recapitulating stem cell functions and potentiating therapeutic actions of bioactive molecules. Moreover, the positions of appropriate bioactive matrices relative to the injury site may stimulate the innate regenerative stem cell populations, removing the need to deliver cells that have been manipulated outside of the body. In this topical review, we update views on advanced designs of biomatrices-including mimicking of the native extracellular matrix, providing mechanical stimulation, activating cell-driven matrices, and delivering bioactive factors in a controllable manner-which are ultimately useful for the regenerative therapy of periodontal tissues. PMID- 25139366 TI - The dynamic impact of repeated stress on the hippocampal spatial map. AB - Stress alters the function of many physiological processes throughout the body, including in the brain. A neural circuit particularly vulnerable to the effects of stress is the hippocampus, a key component of the episodic and spatial memory system in both humans and rodents. Earlier studies have provided snapshots of morphological, molecular, physiological and behavioral changes in the hippocampus following either acute or repeated stress. However, the cumulative impact of repeated stress on in vivo hippocampal physiology remains unexplored. Here we report the stress-induced modulation of the spatially receptive fields of the hippocampal CA1 'place cells' as mice explore familiar and novel tracks after 5 and 10 days of immobilization stress. We find that similar to what has been observed following acute stress, five days of repeated stress results in decreased excitability of CA1 pyramidal cells. Following ten days of chronic stress, however, this decreased hippocampal excitability is no longer evident, suggesting adaptation may have occurred. In addition to these changes in neuronal excitability, we find deficient context discrimination, wherein both short-term and chronic stress impair the ability of the hippocampus to unambiguously distinguish novel and familiar environments. These results suggest that a loss of network flexibility may underlie some of the behavioral deficits accompanying chronic stress. PMID- 25139367 TI - Long-term prevention of postoperative Crohn's disease recurrence with azathioprine: the wolf in the sheep clothing. PMID- 25139368 TI - Amyloidosis presenting as a colonic mass. A case report. PMID- 25139365 TI - Biomaterials for craniofacial bone engineering. AB - Conditions such as congenital anomalies, cancers, and trauma can all result in devastating deficits of bone in the craniofacial skeleton. This can lead to significant alteration in function and appearance that may have significant implications for patients. In addition, large bone defects in this area can pose serious clinical dilemmas, which prove difficult to remedy, even with current gold standard surgical treatments. The craniofacial skeleton is complex and serves important functional demands. The necessity to develop new approaches for craniofacial reconstruction arises from the fact that traditional therapeutic modalities, such as autologous bone grafting, present myriad limitations and carry with them the potential for significant complications. While the optimal bone construct for tissue regeneration remains to be elucidated, much progress has been made in the past decade. Advances in tissue engineering have led to innovative scaffold design, complemented by progress in the understanding of stem cell-based therapy and growth factor enhancement of the healing cascade. This review focuses on the role of biomaterials for craniofacial bone engineering, highlighting key advances in scaffold design and development. PMID- 25139369 TI - Fatal case of hepatic portal venous gas following palliative stenting and chemotherapy for occlusive advanced colorectal cancer. PMID- 25139370 TI - Mesenteric fibromatosis. AB - Mesenteric fibromatosis is a rare, locally invasive, non-metastasizing type of intra-abdominal fibromatoses with a very high rate of recurrence. Because of rarity, these tumors pose a diagnostic and therapeutic challenge. These tumors may remain asymptomatic, but commonly present as a painless mass. There are no clear treatment guidelines. Surgical excision with wide margin is the preferred modality of treatment. Medical therapy is indicated for inoperable and recurrent tumors. There are several isolated case reports on mesenteric fibromatosis with different and unusual presentations and its complications. Though several studies have been published on extra-abdominal fibromatosis as well as on extramesenteric abdominal fibromatosis, but extensive research studies are still lacking on mesenteric fibromatosis. The aim of this article is to present current knowledge on mesenteric fibromatosis, our experience of four cases, and comprehensive review of available literature. PMID- 25139371 TI - Structural modification of plasma albumin in sickle cell anemia. PMID- 25139372 TI - Long-term observation of the vitreomacular relationship in normal fellow eyes of patients with unilateral idiopathic macular holes. AB - PURPOSE: To describe long-term changes in the vitreomacular relationship in normal fellow eyes of patients with unilateral idiopathic macular holes (MHs). METHODS: This is a retrospective, observational case series. The medical records of patients who underwent surgery for idiopathic MHs between May 2000 and December 2010 were reviewed. Patients who had clinically normal fellow eyes and underwent 12 months or more of follow-up were included. The vitreomacular relationship in the fellow eyes was evaluated using optical coherence tomography (OCT) and slit-lamp biomicroscopy. RESULTS: The study included 153 patients with a mean age of 65.5 years and a mean follow-up of 33.5 months (range, 12-121). The incidence of vitreomacular attachments evaluated by OCT was 52% (80 eyes) at initial examination, which decreased to 41, 37 and 23% at 1, 2 and 3 years after the initial examination, respectively. Of the 80 eyes with vitreomacular attachments at initial examination, 40 (50%) still had vitreomacular attachments at the final visit. Of the remaining 40 eyes in which vitreomacular separation occurred during follow-up, 11 (28%) developed an MH, with a mean interval of 45 months. None of the eyes with vitreomacular separation at presentation developed an MH. CONCLUSION: This largest series of fellow eyes of MHs followed by OCT shows that, at presentation, about half of the patients already have premacular vitreous detachment and therefore no risk of MH, and that second MH develops in about 30% in the process of vitreomacular separation, which evolves over a prolonged period. PMID- 25139373 TI - Results from a secondary data analysis regarding satisfaction with health care among African American women living with HIV/AIDS. AB - OBJECTIVE: To analyze satisfaction with health care among African American women living with HIV/AIDS. DESIGN: Secondary analysis of baseline data of African American women who participated in Protect and Respect, a sexual risk reduction program for women living with HIV/AIDS SETTING: HIV Care Clinic in an urban city in the northeast United States. PARTICIPANTS: One hundred fifty-seven (157) African American women living with HIV/AIDS. METHODS: Regression analyses were used to examine the relationships between demographic variables, self-reported health characteristics, communication with health care providers, and satisfaction with health care provider. RESULTS: A majority of women reported satisfaction with medical services (88%, n = 140). Communication with health care providers, detectable viral load, education, income, self-reported health status, and sexual orientation were significantly bivariately associated with satisfaction with healthcare (all ps < .05). In the multivariate models, no variables significantly predicted satisfaction with healthcare. CONCLUSION: Because satisfaction with health care can influence the quality of care received, health outcomes, and adherence to provider recommendations among patients living with HIV/AIDS, health care providers' ability to elicit satisfaction from their patients is just as important as the services they provide. This project is one of the first studies to find high rates of satisfaction with health care among African American women living with HIV/AIDS. Further examination of satisfaction with health care among African American women living HIV/AIDS may help in narrowing health care disparities and negative treatment outcomes. PMID- 25139374 TI - Globalization and eating disorder risk: peer influence, perceived social norms, and adolescent disordered eating in Fiji. AB - OBJECTIVE: The increasing global health burden imposed by eating disorders warrants close examination of social exposures associated with globalization that potentially elevate risk during the critical developmental period of adolescence in low- and middle-income countries (LMICs). The study aim was to investigate the association of peer influence and perceived social norms with adolescent eating pathology in Fiji, a LMIC undergoing rapid social change. METHOD: We measured peer influence on eating concerns (with the Inventory of Peer Influence on Eating Concerns; IPIEC), perceived peer norms associated with disordered eating and body concerns, perceived community cultural norms, and individual cultural orientations in a representative sample of school-going ethnic Fijian adolescent girls (n = 523). We then developed a multivariable linear regression model to examine their relation to eating pathology (measured by the Eating Disorder Examination-Questionnaire; EDE-Q). RESULTS: We found independent and statistically significant associations between both IPIEC scores and our proxy for perceived social norms specific to disordered eating (both p < .001) and EDE Q global scores in a fully adjusted linear regression model. DISCUSSION: Study findings support the possibility that peer influence as well as perceived social norms relevant to disordered eating may elevate risk for disordered eating in Fiji, during the critical developmental period of adolescence. Replication and extension of these research findings in other populations undergoing rapid social transition--and where globalization is also influencing local social norms--may enrich etiologic models and inform strategies to mitigate risk. PMID- 25139376 TI - Exploration of yttria films as gate dielectrics in sub-50 nm carbon nanotube field-effect transistors. AB - Thin yttria films were investigated for use as gate dielectrics in carbon nanotube field-effect transistors (CNTFETs) with the gate length scaled down to sub-50 nm size. The yttria film provided an omega-shaped gate dielectric with a low interface trap density, a low average sub-threshold swing of 74 mV per decade for both long and short CNTFETs, and a small drain-induced barrier lowering. It was also shown that the performance of CNTFETs increases with decreasing temperature, with an excellent sub-threshold swing of 22 mV per decade at liquid nitrogen temperatures. A method was developed to retrieve the interface trap density in CNTFETs and a low interface trap density of 5.2 * 10(6) cm(-1) was achieved, indicating the high electric quality of the yttria films. PMID- 25139375 TI - Impaired autophagy: a link between neurodegenerative and neuropsychiatric diseases. AB - Protein misfolding, and subsequent aggregation have been proven as the leading cause of most known dementias. Many of these, in addition to neurodegeneration, show profound changes in behaviour and thinking, thus, psychiatric symptoms. On the basis of the observation that progressive myoclonic epilepsies and neurodegenerative diseases share some common features of neurodegeneration, we proposed autophagy as a possible common impairment in these diseases. Here, we argue along similar lines for some neuropsychiatric conditions, among them depression and schizophrenia. We propose that existing and new therapies for these seemingly different diseases could be augmented with drugs used for neurodegenerative or neuropsychiatric diseases, respectively, among them some which modulate or augment autophagy. PMID- 25139377 TI - Transient tasks and enduring emotions: the impacts of affective content, task relevance, and picture duration on the sustained late positive potential. AB - The present experiments were designed to examine the influences of picture duration, task relevance, and affective content on neural measures of sustained engagement, as indexed by the late positive potential (LPP). Much prior work has shown that the event-related potential in and around the P3-here referred to as the early LPP-is modulated by affective content, nonaffective task relevance, and stimulus duration. However, later portions of the LPP (>1,000 ms) may represent either a return to baseline or a continued physiological process related to motivational engagement. In the present experiments, we tested whether modulation of the later LPP depends on varying motivational engagement using stimulus duration, affective content, and task relevance. The results of Experiment 1 revealed that stimulus duration modulates the sustained LPP (i.e., 1,000-2,000 ms) in response to affective, but not task-relevant, stimuli from a modified counting oddball task. The results of Experiment 2 revealed that the sustained increase in the LPP is sensitive to both emotional content and task relevance when the task requires sustained engagement with target stimuli (e.g., determining the duration of stimulus presentation). The impacts of emotional content and task relevance had additive effects on the later portion of the LPP. In sum, both emotional content and task relevance can result in a protracted increase in the later LPP. These data suggest that affective content automatically sustains engagement, whereas task relevance only prolongs engagement when it is necessary for task completion. PMID- 25139378 TI - Stability of noble-gas-bound SiH3+ clusters. AB - The stability of noble gas (Ng)-bound SiH3(+) clusters is explored by ab initio computations. Owing to a high positive charge (+1.53 e(-)), the Si center of SiH3(+) can bind two Ng atoms. However, the Si-Ng dissociation energy for the first Ng atom is considerably larger than that for the second one. As we go down group 18, the dissociation energy gradually increases, and the largest value is observed for the case of Rn. For NgSiH3(+) clusters, the Ar-Rn dissociation processes are endergonic at room temperature. For He and Ne, a much lower temperature is required for it to be viable. The formation of Ng2SiH3(+) clusters is also feasible, particularly for the heavier members and at low temperature. To shed light on the nature of Si-Ng bonding, natural population analysis, Wiberg bond indices computations, electron-density analysis, and energy-decomposition analysis were performed. Electron transfer from the Ng centers to the electropositive Si center occurs only to a small extent for the lighter Ng atoms and to a somewhat greater extent for the heavier analogues. The Si-Xe/Rn bonds can be termed covalent bonds, whereas the Si-He/Ne bonds are noncovalent. The Si Ar/Kr bonds possess some degree of covalent character, as they are borderline cases. Contributions from polarization and charge transfer and exchange are key terms in forming Si-Ng bonds. We also studied the effect of substituting the H atoms of SiH3(+) by halide groups (-X) on the Ng binding ability. SiF3(+) showed enhanced Ng binding ability, whereas SiCl3(+) and SiBr3(+) showed a lower ability to bind Ng than SiH3(+). A compromise originates from the dual play of the inductive effect of the -X groups and X->Si pi backbonding (p(z)-p(z) interaction). PMID- 25139379 TI - Use of biosimilars in inflammatory bowel disease: Statements of the Italian Group for Inflammatory Bowel Disease. AB - The introduction of biological therapies, particularly anti-TNFalpha agents, has revolutionized the management of inflammatory bowel disease in those cases which are refractory to conventional treatment; however these drugs are not risk-free and their use has substantially increased the cost of treatment. As marketing protection expires for original, first-generation biopharmaceuticals, lower-cost "copies" of these drugs produced by competitor companies-referred to as biosimilars-are already entering the market. In September 2013, the European Medicines Agency approved two infliximab biosimilars for treatment of adult and paediatric inflammatory bowel disease patients, a decision based largely on efficacy and safety data generated in studies of patients with ankylosing spondylitis and rheumatoid arthritis. For many clinicians, extrapolation practices and the general question of interchangeability between biosimilars and reference biologics are cause for concern. In the present paper, the Italian Group for inflammatory bowel disease presents its statements on these issues, with emphasis on the peculiar clinical characteristics of inflammatory bowel disease and the importance of providing physicians and patients with adequate information and guarantees on the safety and efficacy of these new drugs in the specific setting of inflammatory bowel disease. PMID- 25139380 TI - Thymoglobulin induction in kidney transplantation. PMID- 25139381 TI - Preservation of donor hearts using hypothermic oxygenated perfusion. AB - BACKGROUND: Hypothermic machine perfusion of donor hearts enables continuous aerobic metabolism and washout of toxic metabolic byproducts. We evaluated the effect of machine perfusion on cardiac myocyte integrity in hearts preserved for 4 h in a novel device that provides pulsatile oxygenated hypothermic perfusion (Paragonix Sherpa PerfusionTM Cardiac Transport System). MATERIAL AND METHODS: Pig hearts were harvested and stored in Celsior(r) solution for 4 h using either conventional cold storage on ice (4-h CS, n=6) or the Sherpa device (4-h pulsatile perfusion (PP), n=6). After cold preservation, hearts were evaluated using a non-working heart Langendorff system. Controls (n=3) were reperfused immediately after organ harvest. Biopsies were taken from the apex of the left ventricle before storage, after storage, and after reperfusion to measure ATP content and endothelin-1 in the tissue. Ultrastructural analysis using electron microscopy was performed. RESULTS: Four-hour CS, 4-h PP, and control group did not show any significant differences in systolic or diastolic function (+dP/dt, dP/dt, EDP). Four-hour PP hearts showed significantly more weight gain than 4-h CS after preservation, which shows that machine perfusion led to myocardial edema. Four-hour CS led to higher endothelin-1 levels after preservation, suggesting more endothelial dysfunction compared to 4-h PP. Electron microscopy revealed endothelial cell rupture and damaged muscle fibers in the 4-h CS group after reperfusion, but the cell structures were preserved in the 4-h PP group. CONCLUSIONS: Hypothermic pulsatile perfusion of donor hearts leads to a better preserved cell structure compared to the conventional cold storage method. This may lead to less risk of primary graft failure after orthotopic heart transplantation. PMID- 25139382 TI - A cytoprotective and degradable metal-polyphenol nanoshell for single-cell encapsulation. AB - Single-cell encapsulation promises the cytoprotection of the encased cells against lethal stressors, reminiscent of the sporulation process in nature. However, the development of a cytocompatible method for chemically mimicking the germination process (i.e., shell degradation on-demand) has been elusive, despite the shell degradation being pivotal for the practical use of functional cells as well as for single cell-based biology. We report that an artificial shell, composed of tannic acid (TA) and Fe(III) , on individual Saccharomyces cerevisiae controllably degrades on-demand, while protecting the yeast from multiple external aggressors, including UV-C irradiation, lytic enzymes, and silver nanoparticles. Cell division is suppressed by the TA-Fe(III) shell, but restored fully upon shell degradation. The formation of a TA-Fe(III) shell would provide a versatile tool for achieving the chemical version of "sporulation and germination". PMID- 25139383 TI - Factor structure and gender stability in the multidimensional condom attitudes scale. AB - Sexually transmitted infections continue to trouble the United States and can be attenuated through increased condom use. Attitudes about condoms are an important multidimensional factor that can affect sexual health choices and have been successfully measured using the Multidimensional Condom Attitudes Scale (MCAS). Such attitudes have the potential to vary between men and women, yet little work has been undertaken to identify if the MCAS accurately captures attitudes without being influenced by underlying gender biases. We examined the factor structure and gender invariance on the MCAS using confirmatory factor analysis and item response theory, within-subscale differential item functioning analyses. More than 770 participants provided data via the Internet. Results of differential item functioning analyses identified three items as differentially functioning between the genders, and removal of these items is recommended. Findings confirmed the previously hypothesized multidimensional nature of condom attitudes and the five-factor structure of the MCAS even after the removal of the three problematic items. In general, comparisons across genders using the MCAS seem reasonable from a methodological standpoint. Results are discussed in terms of improving sexual health research and interventions. PMID- 25139384 TI - A multimodal examination of emotional responding to a trauma-relevant film among traumatic motor vehicle accident survivors. AB - The Facial Action Coding System (Ekman & Friesen) has shown promise as a behavioral measure of emotional experience. The current study examined the degree of (de)synchrony between self-reported and facial expressions of fear, disgust, and sadness in response to a traumatic event-relevant film among individuals who had experienced a traumatic motor vehicle accident. Given high rates of comorbidity between posttraumatic stress symptoms (PTSS) and depressive symptoms, the potential impacts of both PTSS and depressive symptoms on emotional responding were examined. Results demonstrated synchrony between self-reported and facial expressions of disgust and sadness; however, no association between measures of fear was observed. Furthermore, depressive symptoms were associated with greater fear responding and PTSS were associated only with self-reported fear. Together, results support the importance of examining discrete negative emotions, rather than broad valence categories, when examining fear-based responding in traumatic event-exposed populations. Additional research examining the psychometric properties of the Facial Action Coding System as a measure of discrete emotional experiences among traumatic event-exposed individuals is needed to advance multimodal assessment approaches that yield incremental information for understanding emotional responding in this population. PMID- 25139385 TI - Oculopalatal tremor: variations on a theme by Guillain and Mollaret. AB - BACKGROUND: Oculopalatal tremor (OPT) is a delayed complication of a brainstem lesion, characterized by involuntary contractions of the soft palate associated with a synchronized ocular pendular nystagmus. MRI reveals inferior olivary nucleus hypersignal/hypertrophy (IONH). Our objective was to refine the clinical profile of patients with OPT and to report a few oddities in both presentation and evolution. METHODS: We performed a retrospective study of patients diagnosed with OPT and a literature search. RESULTS: From our database, we retrieved 5 men and 3 women with a diagnosis of OPT. Eighty-two patients with OPT were retrieved from the literature and were compiled with our series. The average age was 54 years and there was a male predominance. Brainstem vascular lesion was the most common etiology (80%). Prominent vertical pendular nystagmus was found in 90%. Dissociated nystagmus was mostly associated to unilateral contralateral IONH on MRI, while bilateral symmetrical nystagmus was due to a bilateral IONH in the majority of cases. Three oddities were found amongst our 8 patients: prominent nystagmus ipsilateral to IONH; disappearance of IONH on MRI despite persisting nystagmus, and asymptomatic OPT. CONCLUSION: The clinical profile of OPT is rather stereotyped. Rarely do patients deviate from the classical description of OPT. PMID- 25139386 TI - [Medicines for children and "off-label use" 5 years after implementation of the Paediatric Regulation (EC) No 1901/2006. An interim analyis]. AB - Regulation EC 1901/2006, better known as the "Paediatric Regulation," targets the challenging aim of improving the supply of pharmaceutical products for children and adolescents living in Europe. In order to counteract the much-debated and long-standing problem of "off-label" use within paediatrics, the Paediatric Regulation established two new paediatric procedures in order to increase the number of medicines licensed for children in future. This article reports on the outcomes of these procedures, covering the period from 2007 to the present. The aim was to find out how many substances underwent the paediatric procedures and how many medicinal products have been approved explicitly for children as a result. In the second part, a prioritized off-label analysis was conducted focusing on the top 100 substances most frequently prescribed to children and adolescents in Germany in 2011. The top 100 substances consist of the respective top 20 substances of five therapeutic areas. The prescription scores are based on the GAmSi project of the National Association of the Statutory Health Insurance of Germany. The rankings refer to outpatient care and cover the statutory health insured paediatric population of Germany below 18 years of age, divided into two age groups, children and adolescents. In order to investigate whether the most frequently prescribed substances are labelled for paediatric use, 200 SmPCs were screened and evaluated (cut-off date: 31 December 2012). In a final step, the relation between the top 100 substances and the Paediatric Regulation was examined. For this purpose, it was investigated whether the listed substances are or have been subject to the paediatric procedures in order to identify potential positive impacts of the Paediatric Regulation. PMID- 25139388 TI - Advanced kinetic analysis as a tool for formulation development and prediction of vaccine stability. AB - We have used a protein-based vaccine, a live virus vaccine, and an experimental adjuvant to evaluate the utility of an advanced kinetic modeling approach for stability prediction. The modeling approach uses a systematic and simple procedure for the selection of the most appropriate kinetic equation to describe the degradation rate of compounds subjected to accelerated conditions. One-step and two-step reactions with unlimited combinations of kinetic models were screened for the three products under evaluation. The most appropriate mathematical model for a given product was chosen based on the values of residual sum of squares and the weight parameter w. A relatively simple n-th order kinetic model best fitted the degradation of an adjuvanted protein vaccine with a prediction error lower than 10%. A more complex two-step model was required to describe inactivation of a live virus vaccine under normal and elevated storage temperatures. Finally, an autocatalytic-type kinetic model best fitted the degradation of an oil-in-water adjuvant formulation. The modeling approach described here could be used for vaccine stability prediction, expiry date estimation, and formulation selection. To the best of our knowledge, this is the first report describing a global kinetic analysis of degradation of vaccine components with high prediction accuracy. PMID- 25139387 TI - Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells. AB - ABT-737 inhibits the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and BCL X(L). Meayamycin B switches the splicing pattern of myeloid cell leukemia factor 1 (MCL1) pre-mRNA. Specifically, inhibition of splicing factor 3B subunit 1 (SF3B1) with meayamycin B promotes the generation of the proapoptotic, short splicing variant (MCL1-S) and diminishes the antiapoptotic, long variant (MCL1 L). This action was previously associated with the cytotoxicity of meayamycin B in non-small cell lung carcinoma cell lines. ABT-737 induced apoptosis in response to an ablation of MCL1-L by meayamycin B. In this study, we further exploited this synergistic combination in head and neck squamous cell carcinoma (HNSCC), up to 90% of which overexpress MCL1 and BCL-X(L). In a panel of seven HNSCC cell lines, the combination of meayamycin B and ABT-737 rapidly triggered a Bax/Bak-mediated apoptosis that overcame the resistance from HPV16-positive HNSCC against each agent alone. Both RT-PCR and Western blotting showed that meayamycin B up-regulated MCL1-S and down-regulated MCL1-L. Significantly, we discovered that SF3B1 was involved in the splicing of oncogenic HPV16 E6 to produce non oncogenic HPV16 E6*, indicating that SF3B1 may inhibit HPV16-induced tumorigenesis. PMID- 25139389 TI - Public health implications of obstructive sleep apnea burden. AB - OBJECTIVE: To assess the implications of obstructive sleep apnea (OSA) burden among Indian children. METHODS: MonteCarlo simulations were performed in order to estimate the number of OSA related obesity cases among Indian children (1-14 y of age) and the number of cases of stroke, coronary heart disease (CHD) and type 2 diabetes, considered as main adverse outcomes of OSA related childhood obesity, according to untreated and treated [adenotonsillectomy (AT) alone and AT associated to continuous positive airway pressure (CPAP)] pediatric OSA. Data used to perform MonteCarlo simulations were derived from a review about current literature exploring OSA related obesity. RESULTS: The analysis on the number of adverse outcomes according to treated and untreated obesity related to OSA showed that treatments reduce the number of obesity cases, resulting in a great reduction of the amount of stroke, CHD and type 2 diabetes cases. However, the cost for treating adverse outcome was higher in patients treated for obesity related to OSA compared to those not receiving any treatment. CONCLUSIONS: The reduction in the number of adverse outcomes due to treatment of obesity related OSA implicates the urgent need for public health policies in providing screening for OSA among children population: an early detection and a consequently prompt reaction to pediatric OSA could improve the burden of OSA related obesity. PMID- 25139390 TI - Cross-regional analysis of multiple factors associated with childhood obesity in India: a national or local challenge? AB - OBJECTIVE: To investigate obesogenic co-causing factors, promoting rise of weight in children, associated to local differences in India. METHODS: Overall 1,680 children, aged 3-11 and balanced by gender, were recruited in school contexts distributed in seven major Indian cities. All children were weighted and measured in order to calculate their BMI. A validated cultural specific questionnaire was administered to children's parents for assessing socio-demographic data, eating habits, physical activity, etc. Furthermore children's brand awareness scores were computed in order to analyze their affiliation towards food-based advertisement. Descriptive statistics of frequencies, duration and intensity of the various factors were performed. Chi-square tests or Wilcoxon signed rank test were used for evaluating significance of differences in factors distribution across Indian cities. RESULTS: Four factors, promoting rise of children's weight, were individuated as associated to urban differences, namely meal times consumed in the family, parents' BMI, brand awareness and physical activity. These aspects exercised a significant impact on children's body size in Kolkata and Chennai. Hyderabad and Mumbai, instead, were the cities where religion played some role in influencing children's weight gain. CONCLUSIONS: Such findings underline the need to frame obesity as a situated phenomenon rather than a national problem. Health policies, implemented in treating and preventing obesity, should be therefore specifically focused on locally situated peculiarities. PMID- 25139391 TI - 18-Electron rule inspired Zintl-like ions composed of all transition metals. AB - Zintl phase compounds constitute a unique class of compounds composed of metal cations and covalently bonded multiply charged cluster anions. Potential applications of these materials in solution chemistry and thermoelectric materials have given rise to renewed interest in the search for new Zintl ions. Up to now these ions have been mostly composed of group 13, 14, and 15 post transition metal elements and no Zintl ions composed of all transition metal elements are known. Using gradient corrected density functional theory we show that the 18-electron rule can be applied to design a new class of Zintl-like ions composed of all transition metal atoms. We demonstrate this possibility by using Ti@Au12(2-) and Ni@Au6(2-) di-anions as examples of Zintl-like ions. Predictive capability of our approach is demonstrated by showing that FeH6(4-) in an already synthesized complex metal hydride, Mg2FeH6, is a Zintl-like ion, satisfying the 18-electron rule. We also show that novel Zintl phase compounds can be formed by using all transition metal Zintl-like ions as building blocks. For example, a two dimensional periodic structure of Na2[Ti@Au12] is semiconducting and nonmagnetic while a one-dimensional periodic structure of Mg[Ti@Au12] is metallic and ferromagnetic. Our results open the door to the design and synthesis of a new class of Zintl-like ions and compounds with potential for applications. PMID- 25139392 TI - Synthesis of novel two-phase Co@SiO2 nanorattles with high catalytic activity. AB - Noble metal nanocatalysts with remarkable catalytic properties have attracted much attention; however, the high cost of these materials limits their industrial applications. Here, we design and prepare Co@SiO2 nanorattles as a mixture of hcp Co and fcc-Co phases as a substitute. The nanorattles exhibit both superior catalytic activity and high stability for the reduction of p-nitrophenol. The reduction rate nearly follows pseudo-first-order kinetics, and the reaction rate constant is as high as 0.815 min(-1) and is maintained at 0.565 min(-1) even after storing for one month, which is higher than that reported for noble metal nanocatalysts. Such an excellent property can be attributed to the novel two phase composition and rattle-type structure. PMID- 25139393 TI - The prevalence and distribution of gastrointestinal parasites of stray and refuge dogs in four locations in India. AB - A gastrointestinal parasite survey of 411 stray and refuge dogs sampled from four geographical and climactically distinct locations in India revealed these animals to represent a significant source of environmental contamination for parasites that pose a zoonotic risk to the public. Hookworms were the most commonly identified parasite in dogs in Sikkim (71.3%), Mumbai (48.8%) and Delhi (39.1%). In Ladakh, which experiences harsh extremes in climate, a competitive advantage was observed for parasites such as Sarcocystis spp. (44.2%), Taenia hydatigena (30.3%) and Echinococcus granulosus (2.3%) that utilise intermediate hosts for the completion of their life cycle. PCR identified Ancylostoma ceylanicum and Ancylostoma caninum to occur sympatrically, either as single or mixed infections in Sikkim (Northeast) and Mumbai (West). In Delhi, A. caninum was the only species identified in dogs, probably owing to its ability to evade unfavourable climatic conditions by undergoing arrested development in host tissue. The expansion of the known distribution of A. ceylanicum to the west, as far as Mumbai, justifies the renewed interest in this emerging zoonosis and advocates for its surveillance in future human parasite surveys. Of interest was the absence of Trichuris vulpis in dogs, in support of previous canine surveys in India. This study advocates the continuation of birth control programmes in stray dogs that will undoubtedly have spill-over effects on reducing the levels of environmental contamination with parasite stages. In particular, owners of pet animals exposed to these environments must be extra vigilant in ensuring their animals are regularly dewormed and maintaining strict standards of household and personal hygiene. PMID- 25139394 TI - Frequency evaluation of different extraction protocols in orthodontic treatment during 35 years. AB - BACKGROUND: Studies that show frequencies of different orthodontic treatment protocols can be used as valuable parameters in the interpretation of treatment tendency with time. The purpose of this retrospective study was to evaluate all orthodontic treatment planning conducted at the Orthodontic Department at Bauru Dental School, University of Sao Paulo, Brazil, since 1973, in order to investigate extraction and non-extraction protocol frequencies selected at each considered period. METHODS: The sample comprised 3,413 records of treated patients and was evaluated according to the protocol choice, divided into 10 groups: Protocol 0 (non-extraction); Protocol 1 (four first premolar extractions); Protocol 2 (two first maxillary and two second mandibular premolars); Protocol 3 (two maxillary premolar extractions); Protocol 4 (four second premolars); Protocol 5 (asymmetric premolar extractions); Protocol 6 (incisor or canine extractions); Protocol 7 (first or second molar extractions); Protocol 8 (atypical extractions) and Protocol 9 (agenesis and previously missing permanent teeth). These protocols were evaluated in seven 5-year intervals: Interval 1 (1973 to 1977); Interval 2 (1978 to 1982); Interval 3 (1983 to 1987); Interval 4 (1988 to 1992); Interval 5 (1993 to 1997); Interval 6 (1998 to 2002); Interval 7 (2003 to 2007). The frequency of each protocol was compared between the seven intervals, using the proportion test (P < 0.05). RESULTS: The results showed that 10 protocol frequencies were significantly different among the 7 time intervals. CONCLUSIONS: The non-extraction protocol frequency increased gradually with consequent reduction of extraction treatments. The four premolar extraction protocol frequency decreased gradually while the two maxillary premolar extraction protocol has maintained the same frequency of indications throughout time. PMID- 25139395 TI - Small-molecule survivin inhibitor YM155 enhances radiosensitization in esophageal squamous cell carcinoma by the abrogation of G2 checkpoint and suppression of homologous recombination repair. AB - BACKGROUND: Survivin is overexpressed in cancer cells and plays a crucial role in apoptosis evasion. YM155, a small-molecule inhibitor of survivin, could enhance the cytotoxicity of various DNA-damaging agents. Here, we evaluated the radiosensitizaion potential of YM155 in human esophageal squamous cell carcinoma (ESCC). METHODS: Cell viability was determined by CCK8 assay. The radiosensitization effect of YM155 was evaluated by clonogenic survival and progression of tumor xenograft. Cell cycle progression was determined by flow cytometric analysis. Radiation-induced DNA double strand break (DSB) and homologous recombination repair (HRR) were detected by the staining of gamma-H2AX and RAD51, respectively. Expression of survivin and cell cycle regulators was detected by Western blot analysis. RESULTS: YM155 induced radiosensitization in ESCC cell lines Eca109 and TE13, associated with the abrogation of radiation induced G2/M checkpoint, impaired Rad51 focus formation, and the prolongation of gamma-H2AX signaling. G2/M transition markers, including the activation of cyclinB1/Cdc2 kinase and the suppression of Cdc2 Thr14/Tyr15 phosphorylation were induced by YM155 in irradiated cells. The combination of YM155 plus irradiation delayed the growth of ESCC tumor xenografts to a greater extent compared with either treatment modality alone. CONCLUSIONS: Our findings suggest that the abrogation of G2 checkpoint and the inhibition of HRR contribute to radiosensitization by YM155 in ESCC cells. PMID- 25139396 TI - Anthocyanins as a potential therapy for diabetic retinopathy. AB - Diabetic retinopathy is one of the most common complications of diabetes. A plethora of literature indicates that oxidative stress may play a central role in the pathogenesis of diabetic retinopathy. One could thus hypothesise that antioxidant therapies may be protective for diabetic retinopathy. Anthocyanins are important natural bioactive pigments responsible for red-blue colour of fruits, leaves, seeds, stems and flowers in a variety of plant species. Apart from their colours, anthocyanins are known to be health-promoting phytochemicals with potential properties useful to protect against oxidative stress in some degenerative diseases. They also have a variety of biological properties including anti-inflammatory, antibacterial, anticancer, and cardio-protective properties. Some reports further suggest a therapeutic role of anthocyanins to prevent and/or protect against ocular diseases but more studies are needed to examine their potential as alternative therapy to diabetic retinopathy. The present article reviews the available literature concerning the beneficial role of anthocyanins in diabetic retinopathy. PMID- 25139397 TI - Primary Urothelial Carcinoma of the Prostate with Glandular Differentiation: A Case Report. AB - A 53-year-old man presented to our department with acute urinary retention and an approximate 8-year history of frequent urination, dysuria, poor urinary stream and nocturia. His prostate-specific antigen (PSA) values were normal (<4 ng/ml) upon repeated testing. The patient was diagnosed with benign prostatic hyperplasia, although there was no significant improvement in his symptoms after treatment with oral finasteride and doxazosin. He then underwent transurethral resection of the prostate in February 2013, and histopathological examination showed adenocarcinoma of the prostate. His treatment regimen included daily oral bicalutamide and subcutaneous injection of Zoladex once per month. Three months later, radical prostatectomy was performed, and a prostate histopathological examination indicated primary urothelial carcinoma with glandular differentiation. His PSA values were normal (<4 ng/ml) before and after the radical prostatectomy. After the second operation, the patient received chemotherapy with gemcitabine and cisplatin. Two months later, magnetic resonance imaging (MRI) indicated local tumor recurrence. The patient was treated with chemotherapy combined with radiotherapy for 2 months, and subsequent MRI results showed that the recurrent tumor volume was significantly reduced. As a result, radiotherapy was stopped. The patient remains alive, and his general condition has clearly improved. PMID- 25139398 TI - Prognostic factors for patients with atypical or malignant meningiomas treated at a single center. AB - The purpose of this study is to summarize our experience in managing patients with an atypical or malignant meningioma at our institution, with a specific focus on determining the prognostic factors for treatment outcome. We reviewed the records of 126 patients with atypical or malignant meningiomas from January 2001 to August 2011. Data collected included gender, age, Karnofsky Performance Scale (KPS) score, pathology results, cleavability, and bone invasion. The symptoms and signs were recorded for further outcome analysis. There were 37 malignant meningiomas and 89 atypical meningiomas. Total resection (Simpson grade I-II) was achieved in 80.9% of atypical patients (n = 72) and 67.6% of malignant patients (n = 25). Forty patients (44.9%) in the atypical group underwent radiotherapy after surgery, while 26 (70.2%) patients underwent radiotherapy in the malignant group. The median follow-up duration was 25 months. Patients with a secondary tumor had a much shorter progression-free survival (PFS) than those with a primary tumor in the malignant group. The malignant meningioma group had lower overall survival. Progression-free survival for patients in the malignant group who received postoperative radiotherapy was longer than that for those who did not receive radiotherapy. In conclusion, total resection of the tumor was important because patients with a secondary tumor were much more likely to have recurrence than patients with a primary tumor in the atypical and malignant meningioma groups. Also, radiotherapy should be performed after surgery for a malignant meningioma. PMID- 25139399 TI - Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a potential novel strategy for treatment of CVD. Alirocumab is a fully human PCSK9 monoclonal antibody in phase 3 clinical development. We evaluated the antiatherogenic potential of alirocumab in APOE*3Leiden.CETP mice. Mice received a Western-type diet and were treated with alirocumab (3 or 10 mg/kg, weekly subcutaneous dosing) alone and in combination with atorvastatin (3.6 mg/kg/d) for 18 weeks. Alirocumab alone dose-dependently decreased total cholesterol (-37%; -46%, P < 0.001) and TGs (-36%; -39%, P < 0.001) and further decreased cholesterol in combination with atorvastatin (-48%; -58%, P < 0.001). Alirocumab increased hepatic LDL receptor protein levels but did not affect hepatic cholesterol and TG content. Fecal output of bile acids and neutral sterols was not changed. Alirocumab dose dependently decreased atherosclerotic lesion size (-71%; -88%, P < 0.001) and severity and enhanced these effects when added to atorvastatin (-89%; -98%, P < 0.001). Alirocumab reduced monocyte recruitment and improved the lesion composition by increasing the smooth muscle cell and collagen content and decreasing the macrophage and necrotic core content. Alirocumab dose-dependently decreases plasma lipids and, as a result, atherosclerosis development, and it enhances the beneficial effects of atorvastatin in APOE*3Leiden.CETP mice. In addition, alirocumab improves plaque morphology. PMID- 25139400 TI - Docosahexaenoic acid supplementation modifies fatty acid incorporation in tissues and prevents hypoxia induced-atherosclerosis progression in apolipoprotein-E deficient mice. AB - The n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), displays anti inflammatory properties that may prevent atherosclerosis progression. Exposure of apolipoprotein-E deficient (ApoE(-/-)) mice to chronic intermittent hypoxia (CIH) accelerates atherosclerosis progression. Our aim was to assess DHA supplementation influence on fatty acid incorporation in different tissues/organs and on atherosclerosis progression in ApoE(-/-) mice exposed to CIH. ApoE(-/-) mice were exposed to CIH or normoxia (N) and randomized to four groups (N control, CIH control, N+DHA, and CIH+DHA). DHA-supplementation enhanced DHA and reduced arachidonic acid (AA) contents in tissues/organs. CIH control mice exhibited increased atherosclerosis lesion sizes compared to N control mice. DHA prevented CIH induced atherosclerosis but did not improve atherosclerosis burden in N mice. Aortic matrix metalloproteinase-2 (MMP-2) expression was decreased in CIH+DHA mice (p=0.007). DHA-supplementation prevented CIH-induced atherosclerosis acceleration. This was associated with a decrease of AA incorporation and of aortic MMP-2 gene expression. PMID- 25139401 TI - High blood oxygen affinity in the air-breathing swamp eel Monopterus albus. AB - The Asian swamp eel (Monopterus albus, Zuiew 1793) is a facultative air-breathing fish with reduced gills. Previous studies have shown that gas exchange seems to occur across the epithelium of the buccopharyngeal cavity, the esophagus and the integument, resulting in substantial diffusion limitations that must be compensated by adaptations in others steps of the O2 transport system to secure adequate O2 delivery to the respiring tissues. We therefore investigated O2 binding properties of whole blood, stripped hemoglobin (Hb), two major isoHb components and the myoglobin (Mb) from M. albus. Whole blood was sampled using indwelling catheters for blood gas analysis and determination of O2 equilibrium curves. Hb was purified to assess the effects of endogenous allosteric effectors, and Mb was isolated from heart and skeletal muscle to determine its O2 binding properties. The blood of M. albus has a high O2 carrying capacity [hematocrit (Hct) of 42.4+/-4.5%] and binds O2 with an unusually high affinity (P50=2.8+/ 0.4mmHg at 27 degrees C and pH7.7), correlating with insensitivity of the Hb to the anionic allosteric effectors that normally decrease Hb-O2 affinity. In addition, Mb is present at high concentrations in both heart and muscle (5.16+/ 0.99 and 1.08+/-0.19mg ? g wet tissue-1, respectively). We suggest that the high Hct and high blood O2 affinity serve to overcome the low diffusion capacity in the relatively inefficient respiratory surfaces, while high Hct and Mb concentration aid in increasing the O2 flux from the blood to the muscles. PMID- 25139402 TI - Cold hardiness and deacclimation of overwintering Papilio zelicaon pupae. AB - Seasonally-acquired cold tolerance can be reversed at warm temperatures, leaving temperate ectotherms vulnerable to cold snaps. However, deacclimation, and its underlying mechanisms, has not been well-explored in insects. Swallowtail butterflies are widely distributed but in some cases their range is limited by low temperature and their cold tolerance is seasonally acquired, implying that they experience mortality resulting from deacclimation. We investigated cold tolerance and hemolymph composition of Anise swallowtail (Papilio zelicaon) pupae during overwintering in the laboratory, and after four days exposure to warm temperatures in spring. Overwintering pupae had supercooling points around -20.5 degrees C and survived brief exposures to -30 degrees C, suggesting partial freeze tolerance. Overwintering pupae had hemolymph osmolality of approximately 920 mOsm, imparted by high concentrations of glycerol, K+ and Na+. After exposure to spring warming, supercooling points increased to approximately -17 degrees C, and survival of a 1h exposure to -20 degrees C decreased from 100% to 0%. This deacclimation was associated with decreased hemolymph osmolality and reduced glycerol, trehalose, Na+ and Ca2+ concentrations. We compared cold tolerance of pupae to weather conditions at and beyond the species' northern range boundary. Minimum temperatures at the range boundary approached the lower lethal temperature of pupae, and were colder north of the range, suggesting that cold hardiness may set northern range limits. Minimum temperatures following warm snaps were likely to cause mortality in at least one of the past three years. Cold snaps in the spring are increasing in frequency as a result of global climate change, so are likely to be a significant source of mortality for this species, and other temperate ectotherms. PMID- 25139403 TI - The role of rosiglitazone in the proliferation of vascular smooth muscle cells after experimental subarachnoid hemorrhage. AB - BACKGROUND: Recent evidence has demonstrated that rosiglitazone can attenuate cerebral vasospasm following subarachnoid hemorrhage (SAH). Some studies have shown that rosiglitazone can suppress inflammation and immune responses after SAH. However, the precise molecular mechanisms by which cerebral vasospasm is attenuated is not clear. METHODS: In this study, SAH was created using a "double hemorrhage" injection rat model. Rats were randomly divided into three groups and treated with saline (control group), untreated (SAH group), or treated with rosiglitazone. Using immunocytochemistry, hematoxylin and eosin (HE) staining, and measurement of the basilar artery, we investigated the formation of pathologic changes in the basilar artery, measured the expression of caveolin-1 and proliferating cell nuclear antigen (PCNA), and investigated the role of rosiglitazone in vascular smooth muscle cell (VSMC) proliferation in the basilar artery after SAH. RESULTS: In this study, we observed significant pathologic changes in the basilar artery after experimental SAH. The level of vasospasm gradually increased with time during the 1st week, peaked on day 7, and almost recovered on day 14. After rosiglitazone treatment, the level of vasospasm was significantly attenuated in comparison with the SAH group. Immunocytochemistry staining showed that caveolin-1 expression was significantly increased in the rosiglitazone group, compared with the SAH group. Inversely, the expression of PCNA showed a notable decrease after rosiglitazone treatment. CONCLUSIONS: The results indicate that rosiglitazone can attenuate cerebral vasospasm following SAH. Up-regulation of caveolin-1 by rosiglitazone may be a new molecular mechanism for this response, which is to inhibit proliferation of VSMCs after SAH, and this study may provide a novel insight to prevent delayed cerebral vasospasm (DCVS). PMID- 25139404 TI - Phosphatase of regenerating liver-3 is regulated by signal transducer and activator of transcription 3 in acute myeloid leukemia. AB - Overexpression of protein-tyrosine phosphatase of regenerating liver 3 (PRL-3) has been identified in about 50% of patients with acute myeloid leukemia (AML). The mechanism of regulation of PRL-3 remains obscure. Signal transducer and activator of transcription 3 (STAT3), a latent transcriptional factor, has also been often found to be activated in AML. We first identified STAT3-consensus binding sites in the promoter of PRL-3 genes. Then we experimentally validated the direct binding and transcriptional activation. We applied shRNA-mediated knockdown and overexpression approaches in STAT3(-/-) liver cells and leukemic cells to validate the functional regulation of PRL-3 by STAT3. A STAT3 core signature, derived through data mining from publicly available gene expression data, was employed to correlate PRL-3 expression in large AML patient samples. We discovered that STAT3 binds to the -201 to -210 region of PRL-3, which was conserved between human and mouse. Importantly, PRL-3 protein was significantly reduced in mouse STAT3-knockout liver cells compared with STAT3-wild type counterparts, and ectopic expression of STAT3 in these cells led to a pronounced increase in PRL-3 protein. We demonstrated that STAT3 functionally regulated PRL 3, and STAT3 core signature was enriched in AML with high PRL-3 expression. Targeting either STAT3 or PRL-3 reduced leukemic cell viability. Silencing PRL-3 impaired invasiveness and induced leukemic cell differentiation. In conclusion, PRL-3 was transcriptionally regulated by STAT3. The STAT3/PRL-3 regulatory loop contributes to the pathogenesis of AML, and it might represent an attractive therapeutic target for antileukemic therapy. PMID- 25139405 TI - A trans-outer membrane porin-cytochrome protein complex for extracellular electron transfer by Geobacter sulfurreducens PCA. AB - The multi-heme, outer membrane c-type cytochrome (c-Cyt) OmcB of Geobacter sulfurreducens was previously proposed to mediate electron transfer across the outer membrane. However, the underlying mechanism has remained uncharacterized. In G. sulfurreducens, the omcB gene is part of two tandem four-gene clusters, each is predicted to encode a transcriptional factor (OrfR/OrfS), a porin-like outer membrane protein (OmbB/OmbC), a periplasmic c-type cytochrome (OmaB/OmaC) and an outer membrane c-Cyt (OmcB/OmcC) respectively. Here, we showed that OmbB/OmbC, OmaB/OmaC and OmcB/OmcC of G. sulfurreducens PCA formed the porin cytochrome (Pcc) protein complexes, which were involved in transferring electrons across the outer membrane. The isolated Pcc protein complexes reconstituted in proteoliposomes transferred electrons from reduced methyl viologen across the lipid bilayer of liposomes to Fe(III)-citrate and ferrihydrite. The pcc clusters were found in all eight sequenced Geobacter and 11 other bacterial genomes from six different phyla, demonstrating a widespread distribution of Pcc protein complexes in phylogenetically diverse bacteria. Deletion of ombB-omaB-omcB-orfS ombC-omaC-omcC gene clusters had no impact on the growth of G. sulfurreducens PCA with fumarate but diminished the ability of G. sulfurreducens PCA to reduce Fe(III)-citrate and ferrihydrite. Complementation with the ombB-omaB-omcB gene cluster restored the ability of G. sulfurreducens PCA to reduce Fe(III)-citrate and ferrihydrite. PMID- 25139406 TI - Therapeutic decision making in patients with newly diagnosed low grade glioma. AB - OPINION STATEMENT: Low grade gliomas (LGG) encompass primary brain tumors that are typically well-differentiated and do not exhibit frankly malignant histologic features. These tumors can be further classified by their cellular morphology (eg, oligodendroglioma, pilocytic astrocytoma, etc), which does convey prognostic and therapeutic implications. Typically, low grade gliomas convey an overall better prognosis for patients as opposed to the higher grade primary brain tumors. Surgery for low grade gliomas and timing of such intervention remains controversial. Maximal resection of these tumors appears to prolong progression free survival. Advanced surgical techniques, including language mapping and awake craniotomies, have been shown to decrease morbidity associated with resection of lesions in eloquent areas of the brain. Radiation therapy has been proven effective in increasing time to progression in LGG, and emerging data support a role for combined modality therapy incorporating chemotherapy. Postoperative RT has been shown to have significant benefits with regards to progression free survival. Recent advances in molecular genetic markers, including the combined loss of chromosome arms 1p and 19q, and the mutation of the isocitrate dehydrogenase gene (IDH1/IDH2) have allowed for increased accuracy of predicting susceptibility to chemotherapeutic agents, as well as having some role in determining prognosis. PCV and temozolomide chemotherapy have both been studied when assessing progression free survival for LGG patients. Approaching patients with LGGs can be somewhat daunting given the lack of Class I evidence based protocols. However, significant evidence is now mounting to suggest early, maximal surgical excision; followed by fractionated RT will be the mainstays of treatment. Clearly, additional evidence is also mounting for the addition of chemotherapy in the treatment paradigm for patients with LGGs. PMID- 25139407 TI - Microbial signature profiles of periodontally healthy and diseased patients. AB - AIM: To determine microbial profiles that discriminate periodontal health from different forms of periodontal diseases. METHODS: Subgingival biofilm was obtained from patients with periodontal health (27), gingivitis (11), chronic periodontitis (35) and aggressive periodontitis (24), and analysed for the presence of >250 species/phylotypes using HOMIM. Microbial differences among groups were examined by Mann-Whitney U-test. Regression analyses were performed to determine microbial risk indicators of disease. RESULTS: Putative and potential new periodontal pathogens were more prevalent in subjects with periodontal diseases than periodontal health. Detection of Porphyromonas endodontalis/Porphyromonas spp. (OR 9.5 [1.2-73.1]) and Tannerella forsythia (OR 38.2 [3.2-450.6]), and absence of Neisseria polysaccharea (OR 0.004 [0-0.15]) and Prevotella denticola (OR 0.014 [0-0.49], p < 0.05) were risk indicators of periodontal disease. Presence of Aggregatibacter actinomycetemcomitans (OR 29.4 [3.4-176.5]), Cardiobacterium hominis (OR 14.9 [2.3-98.7]), Peptostreptococcaceae sp. (OR 35.9 [2.7-483.9]), P. alactolyticus (OR 31.3 [2.1-477.2]), and absence of Fretibacterium spp. (OR 0.024 [0.002-0.357]), Fusobacterium naviforme/Fusobacterium nucleatum ss vincentii (OR 0.015 [0.001-0.223]), Granulicatella adiacens/Granulicatella elegans (OR 0.013 [0.001-0.233], p < 0.05) were associated with aggressive periodontitis. CONCLUSION: There were specific microbial signatures of the subgingival biofilm that were able to distinguish between microbiomes of periodontal health and diseases. Such profiles may be used to establish risk of disease. PMID- 25139408 TI - Arabidopsis thaliana IRX10 and two related proteins from psyllium and Physcomitrella patens are xylan xylosyltransferases. AB - The enzymatic mechanism that governs the synthesis of the xylan backbone polymer, a linear chain of xylose residues connected by beta-1,4 glycosidic linkages, has remained elusive. Xylan is a major constituent of many kinds of plant cell walls, and genetic studies have identified multiple genes that affect xylan formation. In this study, we investigate several homologs of one of these previously identified xylan-related genes, IRX10 from Arabidopsis thaliana, by heterologous expression and in vitro xylan xylosyltransferase assay. We find that an IRX10 homolog from the moss Physcomitrella patens displays robust activity, and we show that the xylosidic linkage formed is a beta-1,4 linkage, establishing this protein as a xylan beta-1,4-xylosyltransferase. We also find lower but reproducible xylan xylosyltransferase activity with A. thaliana IRX10 and with a homolog from the dicot plant Plantago ovata, showing that xylan xylosyltransferase activity is conserved over large evolutionary distance for these proteins. PMID- 25139409 TI - ? PMID- 25139410 TI - Burden of carbapenem-resistant organisms in the Frankfurt/Main Metropolitan Area in Germany 2012/2013 - first results and experiences after the introduction of legally mandated reporting. AB - BACKGROUND: The federal state of Hesse, Germany, introduced a laboratory-based reporting scheme for carbapenem-resistant organisms (CROs). METHOD: The results of the first year of mandated reporting of CROs from April 2012 through March 2013 to the Public Health Authority of Frankfurt/Main, responsible for a population of 700,000 inhabitants, are described. RESULTS: Within a period of 12 months 243 CROs were notified to the health authority. Of these 213 isolates had been reported from 16 of the 17 hospitals in Frankfurt/Main, 6 from ambulatory settings and 24 from clinics outside of Frankfurt/Main. Mean incidence rate per 1,000 patient days in hospitals was 0.138 (range 0.02-0.28). CONCLUSION: In Frankfurt/Main almost all hospitals have reported CROs in the study period though the frequency of isolation varies strongly and many facilities only report CROs sporadically. Molecular data indicate a high diversity of different carbapenemases. Autochthonous transmission must be assumed despite the absence of major outbreaks. Rapid and coordinated efforts by clinicians and health departments are crucial to control the spread of CRO infections. The mandatory reporting scheme provides important data to guide the implementation of preventive measures. PMID- 25139411 TI - Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome) infusion. AB - Liposomal amphotericin-B (AmBisome) is now becoming first choice for the treatment of visceral leishmaniasis (kala-azar) patients due to high efficacy and less toxicity. The reported incidence of hypersensitivity reactions to liposomal amphotericin-B (AmBisome), especially during therapy, is very rare. We report two patients with kala-azar: one developed breathing difficulties and hypotension followed by shock and the other had facial angioedema with chest tightness during treatment. Both patients were managed with immediate action of injection: adrenaline, diphenhydramine and hydrocortisone. In our experience, AmBisome can cause severe hypersensitivity reactions that warrant proper support and close supervision. PMID- 25139412 TI - Use of long-acting reversible contraceptives in the UK from 2004 to 2010: analysis using The Health Improvement Network Database. AB - OBJECTIVES: To determine the use of long-acting reversible contraceptives (LARCs) in the UK over the period 2004 to 2010, using the general practice database The Health Improvement Network (THIN). METHODS: Women in THIN, aged 18 to 44 years during 2004 to 2010, who had been registered with their general practitioner for at least five years, with a prescription history of at least one year were included. THIN was searched using the Read and MULTILEX codes for: copper intrauterine devices (Cu-IUDs), the levonorgestrel releasing-intrauterine system (LNG-IUS), progestogen-only implants, and progestogen-only injections. RESULTS: The prevalence of progestogen-only implant use rose from 0.5 to 3.4%, and that of the LNG-IUS from 3.1 to 5.2%. The annual incidence and prevalence of progestogen only implant use increased for all age groups but was most marked in younger women, whereas the use of the LNG-IUS augmented with increasing age. For all women, there was a small decrease in the prevalence of use of Cu-IUDs (from 5.4 to 4.8%) and progestogen-only injections (from 3.6 to 3.2%). CONCLUSIONS: Uptake of progestogen-only implants and the LNG-IUS increased over the period 2004 to 2010 in the UK, but LARC use in young women remains low. PMID- 25139413 TI - PTEN loss-mediated Akt activation increases the properties of cancer stem-like cell populations in prostate cancer. AB - OBJECTIVE: To demonstrate that the PTEN/PI3K/Akt/NF-kappaB pathway plays an important role in regulating the prostate cancer stem-like cell population by upregulating ABCG2. METHODS: Targeted PTEN knockdown in human prostate DU145 and 22Rv1 cells using a small interfering RNA were confirmed by immunoblot analysis using antibodies of PTEN, phospho-Akt, Akt, and alpha-tubulin. Knockdown PTEN DU145 and 22Rv1 cells were augmented, and the stem cell-like properties were examined by cell viability and tumor sphere formation and treated by Akt IV inhibitor to provide the signal transduction pathway. Luciferase activity assays were performed. RESULTS: The knockdown of PTEN in prostate cancer cell lines increased the stem-like properties of the cells, including their sphere-forming ability, stem cell population number, epithelial-mesenchymal transition-related gene expression, and ABCG2 expression. Additionally, PTEN expression was highly associated with elevated expression of phospho-Akt. Treatment with an Akt inhibitor suppressed the PTEN-mediated effects on the properties of these stem like cells as well as drug resistance, ABCG2 expression, and the NF-kappaB pathway. CONCLUSION: The loss of PTEN in prostate cancer cells resulted in an increased PI3K/Akt pathway. Due to the Akt activation, PTEN loss may play an important role in prostate cancer by promoting cancer stemness through a mechanism that involves enhanced NF-kappaB signaling. PMID- 25139414 TI - Etiology, clinical features and management of acute recurrent pancreatitis. AB - OBJECTIVE: To study the etiology and clinical features of acute recurrent pancreatitis (ARP) and to determine its optimal management and outcomes. METHODS: ARP cases among acute pancreatitis patients who were admitted to the West China Hospital, Sichuan University from January 2008 to December 2012 were retrospectively collected. Their etiology, clinical features, treatments and outcomes were analyzed. RESULTS: Of all pancreatitis patients, 8.9% were classified as ARP. The proportions of mild and severe diseases were 85.7% and 14.3%, respectively. The common etiological factors were biliogenic (31.0%), alcohol (26.2%), hyperlipidemia (21.4%) and pancreaticobiliary malformation (15.4%). At first 46 cases were cryptogenic and among them 36 were subsequently confirmed by endoscopic retrograde cholangiopancreatography (ERCP). Among the hyperlipidemic ARP patients, 72.2% failed to routinely monitor and control serum lipids. ERCP was performed in 88 cases, and 48 also required an endoscopic sphincterotomy or calculus removal. Twenty-two patients underwent cholangiopancreatic duct stent placement, and pancreatic necrosectomy was performed on eight severe cases. The overall outcomes indicate that 8.3% of the cases progressed to chronic pancreatitis and 33.3% of the cases receiving etiological treatment were recurrence-free. There were no deaths in this study. CONCLUSIONS: The etiological factors of ARP are similar to those of acute pancreatitis at the first attack. The management of ARP should be fully considered based on etiological investigation. PMID- 25139415 TI - Basosquamous carcinoma: is it an aggressive tumor? AB - Basosquamous carcinoma is a rare cutaneous tumour that is considered an aggressive type of basal cell carcinoma with an increased risk of recurrence and metastases. This impression has been perpetuated in the literature, despite limited scientific data and conflicting results of some authors. This present study was aimed to evaluate the clinical-pathological features of this tumour and follow-up of a series of basosquamous carcinoma. Basosquamous carcinoma patients who underwent surgical excision between January 2000 and February 2012 were analyzed retrospectively. Their medical files were reviewed and the corresponding routinely stained sections (with hematoxylin-eosin) were re-evaluated by two pathologists. Thirty-five patients with basosquamous carcinoma were operated on in this period. Most tumurs were located in the head and neck area (94%), and the mean age of the patients was 69.8 years. Margin involvements were seen in 11 patients (31.4%) and all of them underwent re-excision. There was only one local recurrence. There was neither regional lymph node nor distant metastasis in this series. The recurrence rate of basosquamous carcinoma is found as 4%, lower than that of most other similar studies. Further pathologic studies are needed to better classify basosquamous carcinoma and to increase consistency between the results of studies. Surgical excision and regular follow-up are considered as the treatment of choice. PMID- 25139416 TI - Streptococcus oriloxodontae sp. nov., isolated from the oral cavities of elephants. AB - Two strains were isolated from oral cavity samples of healthy elephants. The isolates were Gram-positive, catalase-negative, coccus-shaped organisms that were tentatively identified as a streptococcal species based on the results of biochemical tests. Comparative 16S rRNA gene sequence analysis suggested classification of these organisms in the genus Streptococcus with Streptococcus criceti ATCC 19642(T) and Streptococcus orisuis NUM 1001(T) as their closest phylogenetic neighbours with 98.2 and 96.9% gene sequence similarity, respectively. When multi-locus sequence analysis using four housekeeping genes, groEL, rpoB, gyrB and sodA, was carried out, similarity of concatenated sequences of the four housekeeping genes from the new isolates and Streptococcus mutans was 89.7%. DNA-DNA hybridization experiments suggested that the new isolates were distinct from S. criceti and other species of the genus Streptococcus. On the basis of genotypic and phenotypic differences, it is proposed that the novel isolates are classified in the genus Streptococcus as representatives of Streptococcus oriloxodontae sp. nov. The type strain of S. oriloxodontae is NUM 2101(T) ( =JCM 19285(T) =DSM 27377(T)). PMID- 25139417 TI - Geobacter soli sp. nov., a dissimilatory Fe(III)-reducing bacterium isolated from forest soil. AB - A novel Fe(III)-reducing bacterium, designated GSS01(T), was isolated from a forest soil sample using a liquid medium containing acetate and ferrihydrite as electron donor and electron acceptor, respectively. Cells of strain GSS01(T) were strictly anaerobic, Gram-stain-negative, motile, non-spore-forming and slightly curved rod-shaped. Growth occurred at 16-40 degrees C and optimally at 30 degrees C. The DNA G+C content was 60.9 mol%. The major respiratory quinone was MK-8. The major fatty acids were C(16:0), C(18:0) and C(16:1)omega7c/C(16:1)omega6c. Strain GSS01(T) was able to grow with ferrihydrite, Fe(III) citrate, Mn(IV), sulfur, nitrate or anthraquinone-2,6 disulfonate, but not with fumarate, as sole electron acceptor when acetate was the sole electron donor. The isolate was able to utilize acetate, ethanol, glucose, lactate, butyrate, pyruvate, benzoate, benzaldehyde, m-cresol and phenol but not toluene, p-cresol, propionate, malate or succinate as sole electron donor when ferrihydrite was the sole electron acceptor. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain GSS01(T) was most closely related to Geobacter sulfurreducens PCA(T) (98.3% sequence similarity) and exhibited low similarities (94.9-91.8%) to the type strains of other species of the genus Geobacter. The DNA-DNA relatedness between strain GSS01(T) and G. sulfurreducens PCA(T) was 41.4 +/- 1.1%. On the basis of phylogenetic analysis, phenotypic characterization and physiological tests, strain GSS01(T) is believed to represent a novel species of the genus Geobacter, and the name Geobacter soli sp. nov. is proposed. The type strain is GSS01(T) ( =KCTC 4545(T) =MCCC 1K00269(T)). PMID- 25139418 TI - Taxonomy and phylogeny of two species of the genus Deviata (Protista, Ciliophora) from China, with description of a new soil form, Deviata parabacilliformis sp. nov. AB - The morphology and morphogenesis of a soil hypotrichous ciliate, Deviata parabacilliformis sp. nov., isolated from northern China, were investigated. D. parabacilliformis measures about 75-210 * 25-60 um in vivo, with an elongate and flexible body. It possesses one right marginal row, two to four left marginal rows and three dorsal kineties. The main morphogenetic features of D. parabacilliformis are: (i) the oral primordium originates de novo; (ii) anlage IV of the opisthe originates from parental frontoventral row V, anlage V originates de novo, and anlage VI forms from frontoventral row VI; and (iii) anlage I of the proter originates from the anterior portion of the parental paroral, anlage II originates from the buccal cirrus, anlage III originates from the parabuccal cirri, anlage IV originates from parental frontoventral row IV and anlage V forms from the anterior of parental frontoventral row VI. The morphology of an edaphic population of another species of the genus Deviata, Deviata bacilliformis (Gelei 1954) Eigner 1995, was also investigated. This work also provides the first record of SSU rRNA gene sequences for species of the genus Deviata. Molecular phylogenetic analysis suggests that Deviata is not monophyletic, and its position is poorly resolved due to weak phylogenetic signal of the 18S marker in the Stichotrichida. PMID- 25139419 TI - Is the Sequential Laser Technique for Twin-to-Twin Transfusion Syndrome Truly Superior to the Standard Selective Technique? A Meta-Analysis. AB - BACKGROUND AND OBJECTIVE: To investigate the efficacy of sequential laser coagulation in the treatment of twin-to-twin transfusion syndrome (TTTS). DATA SOURCES: MEDLINE, EMBASE and the Cochrane Library were systematically searched for comparative studies on the efficacy of sequential versus standard selective laser coagulation for TTTS. The primary outcome measure in these studies was survival of at least one twin, both twins and fetal demise. RESULTS: Three cohort studies comparing the selective laser treatment technique (n = 120) versus the sequential technique (n = 224) in 344 monochorionic twin pregnancies were included. Mean survival of at least one twin was 88% in the selective group versus 92% (p = 0.22) in the sequential group. Mean survival of both twins was lower in the selective group (52%) than in the sequential group (75%) (p = 0.002). Donor fetal demise decreased from 34% in the selective to 10% in the sequential group (p < 0.01), and recipient fetal demise decreased from 16 to 7% (p = 0.02). CONCLUSION: Limited evidence suggests improved double neonatal survival as well as decreased donor and recipient fetal demise with the use of the sequential technique. However, these results are based on small non randomized studies with evident forms of bias and methodological limitations. A randomized controlled trial to assess the efficacy of sequential laser technique is therefore required. PMID- 25139420 TI - Neural processing of recollection, familiarity and priming at encoding: evidence from a forced-choice recognition paradigm. AB - The distinction between neural mechanisms of explicit and implicit expressions of memory has been well studied at the retrieval stage, but less at encoding. In addition, dissociations obtained in many studies are complicated by methodological difficulties in obtaining process-pure measures of different types of memory. In this experiment, we applied a subsequent memory paradigm and a two stage forced-choice recognition test to classify study ERP data into four categories: subsequent remembered (later retrieved accompanied by detailed information), subsequent known (later retrieved accompanied by a feeling of familiarity), subsequent primed (later retrieved without conscious awareness) and subsequent forgotten (not retrieved). Differences in subsequent memory effects (DM effects) were measured by comparing ERP waveform associated with later memory based on recollection, familiarity or priming with ERP waveform for later forgotten items. The recollection DM effect involved a robust sustained (onset at 300 ms) prefrontal positive-going DM effect which was right-lateralized, and a later (onset at 800 ms) occipital negative-going DM effect. Familiarity involved an earlier (300-400 ms) prefrontal positive-going DM effect and a later (500-600 ms) parietal positive-going DM effect. Priming involved a negative-going DM effect which onset at 600 ms, mainly distributed over anterior brain sites. These results revealed a sequence of components that represented cognitive processes underlying the encoding of verbal information into episodic memory, and separately supported later remembering, knowing and priming. PMID- 25139421 TI - Adverse effects of antipsychotics on micro-vascular endothelial cells of the human blood-brain barrier. AB - Although the mechanisms of action of antipsychotics (APs) on neuronal function are well understood, very little is known about their effects on cells of the blood-brain barrier (BBB); one function of which is to limit the access of these amphiphilic compounds to the central nervous system. To address this question we have investigated the cytological and functional effects of four APs: chlorpromazine (CLP), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ), at concentrations typical of high therapeutic dosage on a human brain microvascular endothelial cell (HBMEC) model of the BBB. At ~10 uM all four APs impaired the ability of HBMECs to reduce MTT which was followed by decreased Trypan blue exclusion and increased Lactate dehydrogenase release. These effects were associated with oxidative stress which was partly reversed by incubation in 10mM glutathione. At their EC50 concentrations for MTT reduction, all four APs disrupted cellular ultrastructure and morphology. HAL, CPZ and CLZ increased Caspase -3, -8 and -9 activity, chromatin condensation and fragmentation, data indicative of apoptosis. These events were associated with decreased transcytosis of Evans blue and increased transendothelial potential difference and electrical resistance of this BBB model. These findings suggest that at high therapeutic concentrations, CPZ and CLZ are likely to incur cytoxic effects and apoptosis of BBB endothelia with an impairment of barrier functionality. Such events may underlie the aetiology of neuroleptic associated cerebral oedema and neuroleptic malignant syndrome. PMID- 25139422 TI - Musical phrase boundaries, wrap-up and the closure positive shift. AB - We investigated global integration (wrap-up) processes at the boundaries of musical phrases by comparing the effects of well and non-well formed phrases on event-related potentials time-locked to two boundary points: the onset and the offset of the boundary pause. The Closure Positive Shift, which is elicited at the boundary offset, was not modulated by the quality of phrase structure (well vs. non-well formed). In contrast, the boundary onset potentials showed different patterns for well and non-well formed phrases. Our results contribute to specify the functional meaning of the Closure Positive Shift in music, shed light on the large-scale structural integration of musical input, and raise new hypotheses concerning shared resources between music and language. PMID- 25139423 TI - Polyglutamine-expanded ataxin-3 impairs long-term depression in Purkinje neurons of SCA3 transgenic mouse by inhibiting HAT and impairing histone acetylation. AB - Our previous study using a transgenic mouse model of spinocerebellar ataxia type 3 (SCA3) reported that disease-causing ataxin-3-Q79 caused cerebellar malfunction by inducing transcriptional downregulation. Long-term depression (LTD) of parallel fiber-Purkinje neuron glutamatergic transmission is believed to be a cellular mechanism for motor learning and motor coordination in the cerebellum. Downregulated mRNA expression of calcineurin B, IP3-R1, myosin Va and PLC beta4, which are required for the induction of cerebellar LTD, led to an impairment of LTD induction in Purkinje neurons of SCA3 transgenic mouse. Our study suggested that ataxin-3-Q79 caused hypoacetylation of cerebellar histone H3 or H4 by inhibiting the activity of histone acetyltransferase (HAT) without affecting the activity of histone deacetylase (HDAC). Consistent with the hypothesis that hypoacetylated H3 or H4 histone associated with promoter regions of downregulated genes is the molecular mechanism underlying ataxin-3-Q79-induced transcriptional repression, chromatin immunoprecipitation-quantitative real-time PCR analysis showed hypoacetylation of H3 or H4 histone associated with the proximal promoter of downregulated calcineurin B, IP3-R1, myosin Va or PLC beta4 gene in the cerebellum of SCA3 mouse. HDAC inhibitor sodium butyrate reversed ataxin-3-Q79 induced hypoacetylation of histone H3 or H4 associated with the proximal promoter of calcineurin B, IP3-R1, myosin Va or PLC beta4 gene. Sodium butyrate also prevented ataxin-3-Q79-induced impairment of LTD induction in Purkinje neurons of SCA3 mice. Our results suggest that polyglutamine-expanded ataxin-3-Q79 impairs HAT activity, leading to histone hypoacetylation, downregulated expression of cerebellar genes required for LTD induction and impaired induction of cerebellar LTD in the SCA3 transgenic mouse. PMID- 25139424 TI - What's new in the literature: an update of new research since the original WHS diabetic foot ulcer guidelines in 2006. AB - The objective of the paper was to update the diabetic foot ulcer guidelines that were previously published in 2006. We performed a key word search using MEDLINE and Cochrane reviews for publication between January 2006 and January 2012. Articles that fit the inclusion criteria were reviewed and the previous guidelines were updated. PMID- 25139425 TI - Trophic niche and habitat shifts of sympatric Gerreidae. AB - The diet and mouth growth rates of three Gerreidae species (Eugerres brasilianus, Eucinostomus melanopterus and Diapterus rhombeus) were assessed at different ontogenetic phases (juveniles, sub-adults and adults) in order to detect allometric growth, and whether they are related to habitat and seasonal changes in the Goiana Estuary, north-east Brazil. The importance of each prey for each ontogenetic phase was described using the index of relative importance. The three species showed seasonal ontogenetic shifts in diet and allometric growth of mouth morphology. They also had an exclusively zoobenthic diet, comprising mainly Polychaeta, Copepoda, Ostracoda, Gastropoda and Bivalvia. Mouth development showed a possible influence on diet changes for E. melanopterus. Significant interactions (P < 0.01) were detected among seasons, areas and ontogenetic phases for the most important prey for E. brasilianus and E. melanopterus. Diet overlaps are evidence of intra and interspecific competition among gerreids for specific prey. A conceptual model of the competition and seasonal diet shifts among ontogenetic phases of gerreids is given. The sediment ingested due to the feeding mechanisms of Gerreidae species could also partially explain the ingestion of synthetic items observed for all ontogenetic phases, which indicates one of a myriad effects of human activities (e.g. artisanal fishery) in this estuary. PMID- 25139426 TI - Effect of cooked white rice with high beta-glucan barley on appetite and energy intake in healthy Japanese subjects: a randomized controlled trial. AB - White rice is a dominant grain-based food in Japan, but excess intake of polished rice may cause obesity. Barley is a grain-based food, similar to white rice, but it has the potential to control appetite and reduce energy intake. We investigated the effect of cooked white rice with high beta-glucan barley on appetite and energy intake. The study was conducted as a randomized crossover design with twenty-one healthy Japanese women [mean +/- standard deviation body mass index (BMI) 23.3 +/- 0.7 kg/m(2)]. Subjects consumed a breakfast of cooked white rice with high beta-glucan barley (BAR) or white rice (WR), followed by an ad libitum lunch and dinner. Energy intake was measured at the lunch and the dinner using plate waste. Subjects' perception scores on hunger, fullness, satiety, and prospective food consumption were assessed using a visual analogue scale (VAS) before and after the breakfast, lunch and dinner. BAR significantly reduced the VAS scores of hunger and prospective food consumption, and increased fullness before lunch compared to WR (P = 0.032, 0.019 and 0.038, respectively). Energy intake at lunch and the cumulative energy intake (lunch + dinner) subsequent to BAR consumption were significantly lower than WR (P = 0.035 and 0.021, respectively). BAR was able to modulate appetite and reduce energy intake. The combination of white rice with high beta-glucan barley could play a beneficial role in preventing and treating obesity and other obesity-related metabolic diseases. PMID- 25139427 TI - Molecular cloning of two novel peroxidases and their response to salt stress and salicylic acid in the living fossil Ginkgo biloba. AB - BACKGROUND AND AIMS: Peroxidase isoenzymes play diverse roles in plant physiology, such as lignification and defence against pathogens. The actions and regulation of many peroxidases are not known with much accuracy. A number of studies have reported direct involvement of peroxidase isoenzymes in the oxidation of monolignols, which constitutes the last step in the lignin biosynthesis pathway. However, most of the available data concern only peroxidases and lignins from angiosperms. This study describes the molecular cloning of two novel peroxidases from the 'living fossil' Ginkgo biloba and their regulation by salt stress and salicylic acid. METHODS: Suspension cell cultures were used to purify peroxidases and to obtain the cDNAs. Treatments with salicylic acid and sodium chloride were performed and peroxidase activity and gene expression were monitored. KEY RESULTS: A novel peroxidase was purified, which preferentially used p-hydroxycinnamyl alcohols as substrates and was able to form dehydrogenation polymers in vitro from coniferyl and sinapyl alcohols. Two peroxidase full-length cDNAs, GbPrx09 and GbPrx10, were cloned. Both peroxidases showed high similarity to other basic peroxidases with a putative role in cell wall lignification. Both GbPrx09 and GbPrx10 were expressed in leaves and stems of the plant. Sodium chloride enhanced the gene expression of GbPrx09 but repressed GbPrx10, whereas salicylic acid strongly repressed both GbPrx09 and GbPrx10. CONCLUSIONS: Taken together, the data suggest the participation of GbPrx09 and GbPrx10 in the developmental lignification programme of the cell wall. Both peroxidases possess the structural characteristics necessary for sinapyl alcohol oxidation. Moreover, GbPrx09 is also involved in lignification induced by salt stress, while salicylic acid-mediated lignification is not a result of GbPrx09 and GbPrx10 enzymatic activity. PMID- 25139428 TI - Floral structure of Emmotum (Icacinaceae sensu stricto or Emmotaceae), a phylogenetically isolated genus of lamiids with a unique pseudotrimerous gynoecium, bitegmic ovules and monosporangiate thecae. AB - BACKGROUND AND AIMS: Icacinaceae sensu stricto consist of a group of early branching lineages of lamiids whose relationships are not yet resolved and whose detailed floral morphology is poorly known. The most bizarre flowers occur in Emmotum: the gynoecium has three locules on one side and none on the other. It has been interpreted as consisting of three fertile and two sterile carpels or of one fertile carpel with two longitudinal septa and two sterile carpels. This study focused primarily on the outer and inner morphology of the gynoecium to resolve its disputed structure, and ovule structure was also studied. In addition, the perianth and androecium were investigated. METHODS: Flowers and floral buds of two Emmotum species, E. harleyi and E. nitens, were collected and fixed in the field, and then studied by scanning electron microscopy. Microtome section series were used to reconstruct their morphology. KEY RESULTS: The gynoecium in Emmotum was confirmed as pentamerous, consisting of three fertile and two sterile carpels. Each of the three locules behaves as the single locule in other Icacinaceae, with the placenta of the two ovules being identical, which shows that three fertile carpels are present. In addition, it was found that the ovules are bitegmic, which is almost unique in lamiids, and that the stamens have monosporangiate thecae, which also occurs in the closely related family Oncothecaceae, but is not known from any other Icacinaceae sensu lato so far. CONCLUSIONS: The flowers of Emmotum have unique characters at different evolutionary levels: the pseudotrimerous gynoecium at angiosperm level, the bitegmic ovules at lamiid level and the monosporangiate thecae at family or family group level. However, in general, the floral morphology of Emmotum fits well in Icacinaceae. More comparative research on flower structure is necessary in Icacinaceae and other early branching lineages of lamiids to better understand the initial evolution of this large lineage of asterids. PMID- 25139430 TI - Ophthalmic imaging. AB - INTRODUCTION OR BACKGROUND: The last two decades have seen a revolution in ophthalmic imaging. In this review we present an overview of the breadth of ophthalmic imaging modalities in use today and describe how the role of ophthalmic imaging has changed from documenting abnormalities visible on clinical examination to the detection of clinically silent abnormalities which can lead to an earlier and more precise diagnosis. SOURCES OF DATA: This review is based on published literature in the fields of ophthalmic imaging and with focus on most commonly used imaging modalities. AREAS OF AGREEMENT: New imaging techniques enable non-invasive evaluation of ocular structures at a resolution of a few micrometres. This has led to a re-evaluation of diagnostic criteria for ocular disease, which were previously defined by clinical findings without significant reference to imaging. AREAS OF CONTROVERSY: Lack of formal training and clinical guidelines regarding use of new imaging techniques in diagnosing and monitoring various ocular conditions. Lack of large normative databases and interchangeability issues between different commercial machines can hinder the detection of disease progression. GROWING POINTS: Imaging devices are being constantly refined with improved image capture and image analysis tools. AREAS TIMELY FOR DEVELOPING RESEARCH: Clinical applications of new techniques and devices have yet to be determined using systematic scientific research methods. PMID- 25139431 TI - A multidisciplinary approach to determine factors associated with calf rearing practices and calf mortality in dairy herds. AB - In the Netherlands, an increase in ear-tagged calf mortality (3 days to 1 year of age) in dairy farms was observed. The aim was to determine why calf mortality increased and how to reduce calf mortality in herds with structural high rates. A multi-disciplinary approach was chosen to study this phenomenon. First analysis of census data revealed that the majority of the calves died in the first month of life. In addition, a panel of 236 farmers indicated that the increase in calf mortality might be related to priority, time management and the mind-set of farmers. For that reason a questionnaire was carried out to detect risk factors for mortality among young calves (<1 month) in 100 dairy farms with increased calf mortality compared to 100 dairy farms with stable and below average calf mortality. The results showed that, besides management factors such as IBR and BVDV control, and purchase of cattle, also the answers to statements giving an indication on the farmers' mind-set, were associated with calf mortality. Therefore, a qualitative sociological study on the farmers' identity was conducted by performing in-depth interviews among 30 farmers with structurally high calf mortality rates. Afterwards, the results were communicated with a veterinary advisor who visited the farmers and gave tailored advice. Most of the interviewed farmers believed to have sufficient knowledge and skills regarding calf rearing. The farmers did not share their calf rearing problems with colleagues and advisors but they mentioned to be open to receive advice if not communicated in a reproaching or pedantic way. The sociologist distinguished three different phases of awareness concerning calf mortality among the farmers: (1) farmers who were only partly, or not at all, aware of high calf mortality; (2) farmers who felt powerless because of their inability to find a solution to their problems; and (3) farmers who knew they can be inaccurate when it comes to rearing calves, but were reluctant to change this. With the background information of the farmers' identity it was easier for the veterinary advisor to provide tailored advice resulting in a higher probability of following up. A first evaluation in which calf mortality rates in the six months after providing the advice were monitored, indicated that the advice resulted in reduced mortality. The combination of census data, epidemiological and qualitative sociological research revealed that advisors should be aware of the attitude and mind-set of the farmer and adapt their approach and advice accordingly. PMID- 25139429 TI - Back to the future with the AGP-Ca2+ flux capacitor. AB - BACKGROUND: Arabinogalactan proteins (AGPs) are ubiquitous in green plants. AGPs comprise a widely varied group of hydroxyproline (Hyp)-rich cell surface glycoproteins (HRGPs). However, the more narrowly defined classical AGPs massively predominate and cover the plasma membrane. Extensive glycosylation by pendant polysaccharides O-linked to numerous Hyp residues like beads of a necklace creates a unique ionic compartment essential to a wide range of physiological processes including germination, cell extension and fertilization. The vital clue to a precise molecular function remained elusive until the recent isolation of small Hyp-arabinogalactan polysaccharide subunits; their structural elucidation by nuclear magentic resonance imaging, molecular simulations and direct experiment identified a 15-residue consensus subunit as a beta-1,3-linked galactose trisaccharide with two short branched sidechains each with a single glucuronic acid residue that binds Ca(2+) when paired with its adjacent sidechain. SCOPE: AGPs bind Ca(2+) (Kd ~ 6 MUm) at the plasma membrane (PM) at pH ~5.5 but release it when auxin-dependent PM H(+)-ATPase generates a low periplasmic pH that dissociates AGP-Ca(2+) carboxylates (pka ~3); the consequential large increase in free Ca(2+) drives entry into the cytosol via Ca(2+) channels that may be voltage gated. AGPs are thus arguably the primary source of cytosolic oscillatory Ca(2+) waves. This differs markedly from animals, in which cytosolic Ca(2+) originates mostly from internal stores such as the sarcoplasmic reticulum. In contrast, we propose that external dynamic Ca(2+) storage by a periplasmic AGP capacitor co-ordinates plant growth, typically involving exocytosis of AGPs and recycled Ca(2+), hence an AGP-Ca(2+) oscillator. CONCLUSIONS: The novel concept of dynamic Ca(2+) recycling by an AGP-Ca(2+) oscillator solves the long-standing problem of a molecular-level function for classical AGPs and thus integrates three fields: AGPs, Ca(2+) signalling and auxin. This accounts for the involvement of AGPs in plant morphogenesis, including tropic and nastic movements. PMID- 25139432 TI - A novel method to identify herds with an increased probability of disease introduction due to animal trade. AB - In the design of surveillance, there is often a desire to target high risk herds. Such risk-based approaches result in better allocation of resources and improve the performance of surveillance activities. For many contagious animal diseases, movement of live animals is a main route of transmission, and because of this, herds that purchase many live animals or have a large contact network due to trade can be seen as a high risk stratum of the population. This paper presents a new method to assess herd disease risk in animal movement networks. It is an improvement to current network measures that takes direction, temporal order, and also movement size and probability of disease into account. In the study, the method was used to calculate a probability of disease ratio (PDR) of herds in simulated datasets, and of real herds based on animal movement data from dairy herds included in a bulk milk survey for Coxiella burnetii. Known differences in probability of disease are easily incorporated in the calculations and the PDR was calculated while accounting for regional differences in probability of disease, and also by applying equal probability of disease throughout the population. Each herd's increased probability of disease due to purchase of animals was compared to both the average herd and herds within the same risk stratum. The results show that the PDR is able to capture the different circumstances related to disease prevalence and animal trade contact patterns. Comparison of results based on inclusion or exclusion of differences in risk also highlights how ignoring such differences can influence the ability to correctly identify high risk herds. The method shows a potential to be useful for risk based surveillance, in the classification of herds in control programmes or to represent influential contacts in risk factor studies. PMID- 25139433 TI - I want it all and I want it now: Delay of gratification in preschool children. AB - On the delay-of-gratification choice paradigm, 4-year-olds typically choose the larger, delayed reward, exhibiting delay of gratification, whereas 3-year-olds typically choose the small, immediate reward. Despite this highly replicated finding, the cognitive mechanism(s) underlying 3-year-olds' failure on the choice paradigm remain unclear. Recently, several researchers have proposed the involvement of the "hot" affective system and the "cool" cognitive system in pre schoolers' performance on the choice paradigm. Using this "hot" and "cool" systems framework, we tested 112 3- and 4-year-olds on a modified choice paradigm that was designed to help young children better utilize their "cool" system, allowing them to make more mindful and future-oriented decisions. In the modified paradigm, 3-year-olds made choices consistent with those of 4-year-olds, exhibiting delay of gratification. These findings have important implications for previous theoretical accounts of 3-year-old children's failure to delay gratification. Additionally, they highlight the critical role that the method plays in young children's performance on cognitive paradigms. PMID- 25139434 TI - Population structure and genetic analysis of narrow-clawed crayfish (Astacus leptodactylus) populations in Turkey. AB - The genetic differentiation among Turkish populations of the narrow-clawed crayfish was investigated using a partial sequence of cytochrome oxidase subunit I gene (585 bp) of 183 specimens from 17 different crayfish populations. Median joining network and all phylogenetic analyses disclosed a strong haplotype structure with three prominent clades diverged by a range between 20 and 50 mutations and substantial inter-group pairwise sequence divergence (5.19-6.95 %), suggesting the presence of three distinct clades within the Anatolian populations of Astacus leptodactylus. The divergence times among the three clades of Turkish A. leptodactylus are estimated to be 4.96-3.70 Mya using a molecular clock of 1.4 % sequence divergence per million years, pointing to a lower Pliocene separation. The high level of genetic variability (H d = 95.8 %, pi = 4.17 %) and numerous private haplotypes suggest the presence of refugial populations in Anatolia unaffected by Pleistocene habitat restrictions. The pattern of genetic variation among Turkish A. leptodactylus populations, therefore, suggests that the unrevealed intraspecific genetic structure is independent of geographic tendency and congruent with the previously reported geographic distribution and number of subspecies (A. l. leptodactylus and A. l. salinus) of A. leptodactylus. PMID- 25139435 TI - Mesenchymal stromal cells: the magic Band-Aid? PMID- 25139437 TI - [PROMIS((r)): A platform to evaluate health status and the results of interventions]. PMID- 25139436 TI - Enterovirus 71-induced autophagy increases viral replication and pathogenesis in a suckling mouse model. AB - BACKGROUND: We previously reported that Enterovirus 71 (EV71) infection activates autophagy, which promotes viral replication both in vitro and in vivo. In the present study we further investigated whether EV71 infection of neuronal SK-N-SH cells induces an autophagic flux. Furthermore, the effects of autophagy on EV71 related pathogenesis and viral load were evaluated after intracranial inoculation of mouse-adapted EV71 (MP4 strain) into 6-day-old ICR suckling mice. RESULTS: We demonstrated that in EV71-infected SK-N-SH cells, EV71 structural protein VP1 and nonstructural protein 2C co-localized with LC3 and mannose-6-phosphate receptor (MPR, endosome marker) proteins by immunofluorescence staining, indicating amphisome formation. Together with amphisome formation, EV71 induced an autophagic flux, which could be blocked by NH4Cl (inhibitor of acidification) and vinblastine (inhibitor of fusion), as demonstrated by Western blotting. Suckling mice intracranially inoculated with EV71 showed EV71 VP1 protein expression (representing EV71 infection) in the cerebellum, medulla, and pons by immunohistochemical staining. Accompanied with these infected brain tissues, increased expression of LC3-II protein as well as formation of LC3 aggregates, autophagosomes and amphisomes were detected. Amphisome formation, which was confirmed by colocalization of EV71-VP1 protein or LC3 puncta and the endosome marker protein MPR. Thus, EV71-infected suckling mice (similar to EV71-infected SK-N-SH cells) also show an autophagic flux. The physiopathological parameters of EV71-MP4 infected mice, including body weight loss, disease symptoms, and mortality were increased compared to those of the uninfected mice. We further blocked EV71-induced autophagy with the inhibitor 3-methyladenine (3-MA), which attenuated the disease symptoms and decreased the viral load in the brain tissues of the infected mice. CONCLUSIONS: In this study, we reveal that EV71 infection of suckling mice induces an amphisome formation accompanied with the autophagic flux in the brain tissues. Autophagy induced by EV71 promotes viral replication and EV71-related pathogenesis. PMID- 25139438 TI - Total synthesis and biological studies of cryptocin and derivatives of equisetin and fusarisetin A. AB - Total synthesis of cryptocin, a fungus metabolite, was achieved based on the biosynthetic hypothesis. A variety of derivatives of cryptocin, equisetin and fusarisetin A were prepared, wherein the racemization of C-3 and diastereoselectivity of C-5 were investigated. We further examined their inhibitory effects on breast cancer cell survival and metastasis, and summarized the structure-activity relationship. PMID- 25139440 TI - Novel paracrine modulation of Notch-DLL4 signaling by fibulin-3 promotes angiogenesis in high-grade gliomas. AB - High-grade gliomas are characterized by exuberant vascularization, diffuse invasion, and significant chemoresistance, resulting in a recurrent phenotype that makes them impossible to eradicate in the long term. Targeting protumoral signals in the glioma microenvironment could have significant impact against tumor cells and the supporting niche that facilitates their growth. Fibulin-3 is a protein secreted by glioma cells, but absent in normal brain, that promotes tumor invasion and survival. We show here that fibulin-3 is a paracrine activator of Notch signaling in endothelial cells and promotes glioma angiogenesis. Fibulin 3 overexpression increased tumor VEGF levels, microvascular density, and vessel permeability, whereas fibulin-3 knockdown reduced vessel density in xenograft models of glioma. Fibulin-3 localization in human glioblastomas showed dense fiber-like condensations around tumor blood vessels, which were absent in normal brain, suggesting a remarkable association of this protein with tumor endothelium. At the cellular level, fibulin-3 enhanced endothelial cell motility and association to glioma cells, reduced endothelial cell sprouting, and increased formation of endothelial tubules in a VEGF-independent and Notch dependent manner. Fibulin-3 increased ADAM10/17 activity in endothelial cells by inhibiting the metalloprotease inhibitor TIMP3; this resulted in increased Notch cleavage and increased expression of DLL4 independently of VEGF signaling. Inhibition of ADAM10/17 or knockdown of DLL4 reduced the proangiogenic effects of fibulin-3 in culture. Taken together, these results reveal a novel, proangiogenic role of fibulin-3 in gliomas, highlighting the relevance of this protein as an important molecular target in the tumor microenvironment. PMID- 25139441 TI - Radiation-induced secondary malignancy in prostate cancer: a systematic review and meta-analysis. AB - OBJECTIVE: To investigate the risk of radiation-induced secondary malignancy in patients with prostate cancer. METHODS: We identified 690 references from PubMed, Embase and the Cochrane Library before August 1, 2012, that reported secondary malignancy in patients with prostate cancer after receiving radiation therapy (RT), and finally four studies were included. We calculated summary estimates using random-effects meta-analysis. RESULTS: The overall standardized incidence ratio (SIR) of secondary malignancy in patients with prostate cancer receiving RT to the general population was 1.14 (95% CI 1.04-1.32). In the subgroup analysis, no increment in radiation-induced secondary malignancy risk was detected. In terms of SIR with different follow-up intervals, there was no difference in SIR (>6 months; <5 years) (SIR = 1.19, 95% CI 0.75-1.89) and SIR (>5 years; <10 years) (SIR = 1.39, 95% CI 0.87-2.23). When the follow-up extended to >10 years, a significantly increased secondary malignancy risk was observed (SIR = 1.45, 95% CI 1.23-1.72). There is no significantly increased secondary malignancy risk in patients receiving no RT. CONCLUSION: RT is associated with increased secondary malignancy in patients with prostate cancer; this effect only become conspicuous more than 10 years after treatment. PMID- 25139442 TI - Boron-double-ring sheet, fullerene, and nanotubes: potential hydrogen storage materials. AB - Similar to carbon-based graphene, fullerenes and carbon nanotubes, boron atoms can form sheets, fullerenes, and nanotubes. Here we investigate several of these novel boron structures all based on the boron double ring within the framework of density functional theory. The boron sheet is found to be metallic and flat in its ground state. The spherical boron cage containing 180 atoms is also stable and has I symmetry. Stable nanotubes are obtained by rolling up the boron sheet, and all are metallic. The hydrogen storage capacity of boron nanostructures is also explored, and it is found that Li-decorated boron sheets and nanotubes are potential candidates for hydrogen storage. For Li-decorated boron sheets, each Li atom can adsorb a maximum of 4 H2 molecules with g(d) =7.892 wt %. The hydrogen gravimetric density increases to g(d) =12.309 wt % for the Li-decorated (0,6) boron nanotube. PMID- 25139443 TI - Adult newborn neurons are involved in learning acquisition and long-term memory formation: the distinct demands on temporal neurogenesis of different cognitive tasks. AB - There is evidence that adult hippocampal neurogenesis influences hippocampal function, although the role these neurons fulfill in learning and consolidation processes remains unclear. Using a novel fast X-ray ablation protocol to deplete neurogenic cells, we demonstrate that immature adult hippocampal neurons are required for hippocampal learning and long-term memory formation. Moreover, we found that long-term memory formation in the object recognition and passive avoidance tests, two paradigms that involve circuits with distinct emotional components, had different temporal demands on hippocampal neurogenesis. These results reveal new and unexpected aspects of neurogenesis in cognitive processes. PMID- 25139444 TI - Sudden arrhythmic death syndrome: diagnostic yield of comprehensive clinical evaluation of pediatric first-degree relatives. AB - AIMS: Sudden arrhythmic death syndrome (SADS) is most often caused by heritable cardiac diseases. Studies in adults have identified evidence of inherited cardiovascular diseases in up to 53% of families, but data on the prevalence of familial disease in children are scarce. The aim of this study was to evaluate the yield of clinical screening in pediatric first-degree relatives of victims of SADS using a systematic and comprehensive protocol. METHODS: Patients referred for family screening after sudden cardiac death (SCD) of a family member were, retrospectively, enrolled into the study. Systematic evaluation of the children included clinical examination, family history, electrocardiogram (ECG), echocardiogram, 24-hour tape, and signal-averaged ECG. Older patients also underwent exercise testing, cardiac magnetic resonance imaging, and ajmaline provocation testing. RESULTS: A total of 90 children from 52 consecutive families were included in the study. An inherited cardiac disease was identified in seven first-degree children from seven (13.5%) families (five children were diagnosed with Brugada syndrome, one with long QT syndrome, and one with catecholaminergic polymorphic ventricular tachycardia). Two further children had late potentials on signal-averaged ECGs with no other abnormalities. CONCLUSIONS: These data show a high prevalence of inherited heart disease in pediatric first-degree relatives of SADS victims. The results highlight the importance of a systematic, comprehensive approach and ongoing screening of pediatric family members. PMID- 25139445 TI - Reconfirmation of the anatomy of the left triangular ligament and the appendix fibrosa hepatis in human livers, and its implication in abdominal surgery. AB - BACKGROUND: The aim of the present study was to clarify the anatomy between the left triangular ligament (LTL) and the appendix fibrosa hepatis (AFH) in order not to sever the AFH when dissecting the LTL. METHODS: Totals of 43 and 27 cadaveric livers were examined macroscopically and histologically, respectively. RESULTS: The LTL attached itself to the diaphragmatic surface of the AFH through almost all lengths of the AFH. This might be the reason why AFH is so often dissected together with the LTL. There were two types of relation between the LTL and the AFH; in one type, the starting point of the LTL existed on the left liver and in the other type, it was on the AFH. Twenty-five of 27 AFH included remnants of the bile duct and 12 of 25 AFH had comparatively large bile ducts, which was unexceptionally accompanied by the well-developed peribiliary vascular plexus. AFH showed a variety of shapes, such as rectangular (6/43), long triangular (4/43), short triangular (7/43), triangular plus cordlike (11/43), cordlike (12/43) and bifurcated (3/43) types. CONCLUSIONS: As AFH sometimes includes relatively large bile ducts, it is recommended for surgeons to sever the AFH not just simply by electrocautery but by ligating its stump securely. PMID- 25139446 TI - [Everyday competencies and learning processes in old age. Results and perspectives of the PIAAC extension study "Competencies in later life"]. AB - This article deals with the study "Competencies in later life" (CiLL), a parallel study to the German program for the international assessment of adult competencies (PIAAC) survey which assesses the level and distribution of skills of the adult population in a representative study. Assuming the growing importance of learning and education in a society challenged by demographic changes, the first section of the paper outlines the qualitative research of learning activities of focus groups in the daily life of elderly people. The second section of the paper presents the survey design and exemplary findings of the quantitative CiLL study. Initial results show that basic skills of the elderly are highly influenced by personal and sociodemographic variables, particularly by educational background. The data available indicate that the participation of the elderly in adult education and the options available for competence development have to be increased. PMID- 25139447 TI - Electroactive bacteria--molecular mechanisms and genetic tools. AB - In nature, different bacteria have evolved strategies to transfer electrons far beyond the cell surface. This electron transfer enables the use of these bacteria in bioelectrochemical systems (BES), such as microbial fuel cells (MFCs) and microbial electrosynthesis (MES). The main feature of electroactive bacteria (EAB) in these applications is the ability to transfer electrons from the microbial cell to an electrode or vice versa instead of the natural redox partner. In general, the application of electroactive organisms in BES offers the opportunity to develop efficient and sustainable processes for the production of energy as well as bulk and fine chemicals, respectively. This review describes and compares key microbiological features of different EAB. Furthermore, it focuses on achievements and future prospects of genetic manipulation for efficient strain development. PMID- 25139448 TI - CO2 /HCO3- perturbations of simulated large scale gradients in a scale-down device cause fast transcriptional responses in Corynebacterium glutamicum. AB - The exploration of scale-down models to imitate the influence of large scale bioreactor inhomogeneities on cellular metabolism is a topic with increasing relevance. While gradients of substrates, pH, or dissolved oxygen are often investigated, oscillating CO2/HCO3 (-) levels, a typical scenario in large industrial bioreactors, is rarely addressed. Hereby, we investigate the metabolic and transcriptional response in Corynebacterium glutamicum wild type as well as the impact on L-lysine production in a model strain exposed to pCO2 gradients of (75-315) mbar. A three-compartment cascade bioreactor system was developed and characterized that offers high flexibility for installing gradients and residence times to mimic industrial-relevant conditions and provides the potential of accurate carbon balancing. The phenomenological analysis of cascade fermentations imposed to the pCO2 gradients at industry-relevant residence times of about 3.6 min did not significantly impair the process performance, with growth and product formation being similar to control conditions. However, transcriptional analysis disclosed up to 66 differentially expressed genes already after 3.6 min under stimulus exposure, with the overall change in gene expression directly correlateable to the pCO2 gradient intensity and the residence time of the cells. PMID- 25139449 TI - Revised scheme for the mechanism of photoinhibition and its application to enhance the abiotic stress tolerance of the photosynthetic machinery. AB - When photosynthetic organisms are exposed to abiotic stress, their photosynthetic activity is significantly depressed. In particular, photosystem II (PSII) in the photosynthetic machinery is readily inactivated under strong light and this phenomenon is referred to as photoinhibition of PSII. Other types of abiotic stress act synergistically with light stress to accelerate photoinhibition. Recent studies of photoinhibition have revealed that light stress damages PSII directly, whereas other abiotic stresses act exclusively to inhibit the repair of PSII after light-induced damage (photodamage). Such inhibition of repair is associated with suppression, by reactive oxygen species (ROS), of the synthesis of proteins de novo and, in particular, of the D1 protein, and also with the reduced efficiency of repair under stress conditions. Gene-technological improvements in the tolerance of photosynthetic organisms to various abiotic stresses have been achieved via protection of the repair system from ROS and, also, by enhancing the efficiency of repair via facilitation of the turnover of the D1 protein in PSII. In this review, we summarize the current status of research on photoinhibition as it relates to the effects of abiotic stress and we discuss successful strategies that enhance the activity of the repair machinery. In addition, we propose several potential methods for activating the repair system by gene-technological methods. PMID- 25139450 TI - The dissection profile and mechanism of tissue-selective dissection of the piezo actuator-driven pulsed water jet as a surgical instrument: laboratory investigation using Swine liver. AB - BACKGROUND/PURPOSE: The water jet technique dissects tissue while sparing cord like structures such as blood vessels. The mechanism of such tissue-selective dissection has been unknown. The novel piezo actuator-driven pulsed water jet (ADPJ) system can achieve dissection with remarkably reduced water consumption compared to the conventional water jet; however, the system's characteristics and dissection capabilities on any organ have not been clarified. The purposes of this study were to characterize the physical properties of the novel ADPJ system, evaluate the dissection ability in swine organs, and reveal the mechanism of tissue-selective dissection. METHODS: The pulsed water jet system comprised a pump chamber driven by a piezo actuator, a stainless steel tube, and a nozzle. The peak pressure of the pulsed water jet was measured through a sensing hole using a pressure sensor. The pulsed water jet technique was applied on swine liver in order to dissect tissue on a moving table using one-way linear ejection at a constant speed. The dissection depth was measured with light microscopy and evaluated histologically. The physical properties of swine liver were evaluated by breaking strength tests using tabletop universal testing instruments. The liver parenchyma was also cut with three currently available surgical devices to compare the histological findings. RESULTS: The peak pressure of the pulsed water jet positively correlated with the input voltage (R(2) = 0.9982, p < 0.0001), and this was reflected in the dissection depth. The dissection depth negatively correlated with the breaking strength of the liver parenchyma (R(2) = 0.6694, p < 0.0001). The average breaking strengths of the liver parenchyma, hepatic veins, and Glisson's sheaths were 1.41 +/- 0.45, 8.66 +/- 1.70, and 29.6 +/- 11.0 MPa, respectively. The breaking strength of the liver parenchyma was significantly lower than that of the hepatic veins and Glisson's sheaths. Histological staining confirmed that the liver parenchyma was selectively dissected, preserving the hepatic veins and Glisson's sheaths in contrast to what is commonly observed with electrocautery or ultrasonic instruments. CONCLUSIONS: The dissection depth of liver tissue is well controlled by input voltage and is influenced by the moving velocity and the physical properties of the organ. We showed that the device can be used to assure liver resection with tissue selectivity due to tissue-specific physical properties. Although this study uses an excised organ, further in vivo studies are necessary. The present work demonstrates that this device may function as an alternative tool for surgery due to its good controllability of the dissection depth and ability of tissue selectivity. PMID- 25139451 TI - The use of elemental mass spectrometry in phosphoproteomic applications. AB - Reversible phosphorylation is one of the most important post-translational modifications in mammalian cells. Because this molecular switch is an important mechanism that diversifies and regulates proteins in cellular processes, knowledge about the extent and quantity of phosphorylation is very important to understand the complex cellular interplay. Although phosphoproteomics strategies are applied worldwide, they mainly include only molecular mass spectrometry (like MALDI or ESI)-based experiments. Although identification and relative quantification of phosphopeptides is straightforward with these techniques, absolute quantification is more complex and usually requires for specific isotopically phosphopeptide standards. However, the use of elemental mass spectrometry, and in particular inductively coupled plasma mass spectrometry (ICP MS), in phosphoproteomics-based experiments, allow one to absolutely quantify phosphopeptides. Here, these phosphoproteomic applications with ICP-MS as elemental detector are reviewed. Pioneering work and recent developments in the field are both described. Additionally, the advantage of the parallel use of molecular and elemental mass spectrometry is stressed. PMID- 25139452 TI - Socioecological factors in sexual decision making among urban girls and young women. AB - OBJECTIVES: To examine how girls and young women living in disadvantaged urban neighborhoods make decisions relating to sexual debut and HIV prevention. DESIGN: Thirty semistructured in-depth interviews. We used a socioecological approach to investigate the role of neighborhood and social context on sexual decision making. SETTING: Community-based organizations and on-campus interview sites. PARTICIPANTS: African American and Latina girls and young women age 13 to 24 living in disadvantaged neighborhoods. METHODS: We examine their attitudes and beliefs about sex, first opportunities for sexual intercourse, prevention behaviors, and neighborhood environments. RESULTS: Lack of neighborhood safety and safe socialization places led youth to spend significant amounts of time indoors, often without adult supervision. CONCLUSION: The findings provide insight into the socioecological context in which girls are situated as they navigate sexual decision making. Unsupervised, cloistered time coupled with peer norms to engage in sexual behavior may contribute to increased risky sexual behavior among some youth. Prevention efforts should consider neighborhood context and incorporate structural and community-level interventions to create social environments that support healthy sexual decision making. PMID- 25139453 TI - Can renal ultrasonography predict early success after pyeloplasty in children? A prospective study. AB - OBJECTIVE: To study the predictive value of 6 ultrasonographic (USG) parameters for early detection of children at risk of recurrent obstruction. PATIENTS AND METHODS: A prospective nonrandomized study included all patients who underwent pyeloplasty between 2010 and 2012. All of the patients had completed at least 6 months of follow-up and preoperative and postoperative USG imaging data were available. The primary outcome was the correlation between USG and diuretic scintigraphic parameters. The secondary outcome was the predictive ability of the pelvicalyceal system parameters, measured by USG, of parenchymal growth after surgery. RESULTS: Sixty-eight patients were evaluated. The mean age was 3.6 years (range 0.1-12). The mean (+/- standard deviation) differential renal function improved from 37.4 +/- 11 ml/min to 37.7 +/- 14 ml/min, which was a difference of no statistical significance. On the other hand, the mean (+/- SD) half-time (T1/2) significantly improved. After constructing a linear regression model of the 4 USG parameters and the parenchymal growth, the model explained 57.2% of the variance in parenchymal growth after pyeloplasty. The calyx-to-parenchyma ratio change was the largest unique contribution for explaining the variance in parenchymal growth, followed by anteroposterior diameter and calyceal dilatation. CONCLUSION: We proved that calyx-to-parenchyma ratio, anteroposterior diameter and calyceal dilatation are independent predictors of early success after pyeloplasty. PMID- 25139454 TI - Antibiotic dispensation by Lebanese pharmacists: a comparison of higher and lower socio-economic levels. AB - INTRODUCTION: Indiscriminate use of antibiotics contributes to a global spread of antimicrobial resistance. Previous studies showed an excessive consumption of antibiotics purchased without medical prescription from community pharmacies, mainly in developing countries. There is a shortage of studies revealing the role of community pharmacists in the overuse of antibiotics. Our objective is to study the dispensing policy of non-medical prescription antibiotics in community pharmacies, assessing the possible influence of the socio-economic level of the area over this practice. METHODS: A cross-sectional study was conducted between February and May 2011 among 100 pharmacists working in Beirut's pharmacies and its suburbs. Pharmacies were divided into 2 groups according to the socio economic level of the population living in the pharmacy area. A self-administered questionnaire was filled by pharmacists. RESULTS: Over-the-counter antibiotic availability existed in both higher and lower socio-economic areas: on the whole, 32% of antibiotics were dispensed without medical prescription, with higher frequency in lower socio-economic areas (p=0.003). Dispensing injectable antibiotics without medical prescription was significantly higher in lower socio economic areas (p=0.021), as well as dispensing an association of 2 antibiotics without medical prescription (p=0.001). Pharmacists working in lower socio economic areas recommended more frequent antibiotics to children and the elderly (p<0.001 and p=0.004, respectively). CONCLUSION: Dispensing antibiotics without medical prescription in Beirut community pharmacies is a common practice, particularly in lower socioeconomic areas. This public health problem should be addressed at the social, educational, and legislative levels. PMID- 25139455 TI - Evidence of topological surface state in three-dimensional Dirac semimetal Cd3As2. AB - The three-dimensional topological semimetals represent a new quantum state of matter. Distinct from the surface state in the topological insulators that exhibits linear dispersion in two-dimensional momentum plane, the three dimensional semimetals host bulk band dispersions linearly along all directions. In addition to the gapless points in the bulk, the three-dimensional Weyl/Dirac semimetals are also characterized by "topologically protected" surface state with Fermi arcs on their surface. While Cd3As2 is proposed to be a viable candidate of a Dirac semimetal, more investigations are necessary to pin down its nature. In particular, the topological surface state, the hallmark of the three-dimensional semimetal, has not been observed in Cd3As2. Here we report the electronic structure of Cd3As2 investigated by angle-resolved photoemission measurements on the (112) crystal surface and detailed band structure calculations. The measured Fermi surface and band structure show a good agreement with the band structure calculations with two bulk Dirac-like bands approaching the Fermi level and forming Dirac points near the Brillouin zone center. Moreover, the topological surface state with a linear dispersion approaching the Fermi level is identified for the first time. These results provide experimental indications on the nature of topologically non-trivial three-dimensional Dirac cones in Cd3As2. PMID- 25139456 TI - Prognostic value of midregional pro-A-type natriuretic peptide and N-terminal pro B-type natriuretic peptide in patients with stable coronary heart disease followed over 8 years. AB - BACKGROUND: Pathophysiological studies suggest that A-type natriuretic peptides (ANPs) might provide valuable information beyond B-type natriuretic peptides (BNPs) about cardiac dysfunction in patients with coronary heart disease (CHD). We aimed to assess the predictive value of midregional pro-A-type natriuretic peptide (MR-proANP) for recurrent cardiovascular disease (CVD) events in stable CHD patients for whom information on N-terminal proBNP (NT-proBNP) was already available. METHODS: Plasma concentrations of MR-proANP and NT-proBNP were measured at baseline in a cohort of 1048 patients aged 30-70 years with CHD who were participating in an in-hospital rehabilitation program. Main outcome measures were cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: During a median follow-up of 8.1 years, 150 patients (incidence 21.1 per 1000 patient-years) experienced a secondary CVD event. MR proANP was associated with a hazard ratio (HR) of 1.89 (95% CI, 1.01-3.57) when the top quartile was compared to the bottom quartile in the fully adjusted model (P for trend = 0.011). For NT-proBNP the respective HR was 2.22 (95% CI, 1.19 4.14) with a P for trend = 0.001. Finally, MR-proANP improved various model performance measures, including c-statistics and reclassification metrics, but without being superior to NT-proBNP. CONCLUSIONS: Although we found an independent association of MR-proANP as well as NT-proBNP when used as single markers with recurrent CVD events after adjustment for established risk factors, the results of a simultaneous assessment of both markers indicated that MR-proANP fails to provide additional prognostic information to NT-proBNP in the population studied. PMID- 25139457 TI - Integrative bioinformatics analysis reveals new prognostic biomarkers of clear cell renal cell carcinoma. AB - BACKGROUND: The outcome of clear cell renal cell carcinoma (ccRCC) is still unpredictable. Even with new targeted therapies, the average progression-free survival is dismal. Markers for early detection and progression could improve disease outcome. METHODS: To identify efficient and hitherto unrecognized pathogenic factors of the disease, we performed a uniquely comprehensive pathway analysis and built a gene interaction network based on large publicly available data sets assembled from 28 publications, comprising a 3-prong approach with high throughput mRNA, microRNA, and protein expression profiles of 593 ccRCC and 389 normal kidney samples. We validated our results on 2 different data sets of 882 ccRCC and 152 normal tissues. Functional analyses were done by proliferation, migration, and invasion assays following siRNA (small interfering RNA) knockdown. RESULTS: After integration of multilevel data, we identified aryl-hydrocarbon receptor (AHR), grainyhead-like-2 (GRHL2), and KIAA0101 as new pathogenic factors. GRHL2 expression was associated with higher chances for disease relapse and retained prognostic utility after controlling for grade and stage [hazard ratio (HR), 3.47, P = 0.012]. Patients with KIAA0101-positive expression suffered worse disease-free survival (HR, 3.64, P < 0.001), and in multivariate analysis KIAA0101 retained its independent prognostic significance. Survival analysis showed that GRHL2- and KIAA0101-positive patients had significantly lower disease free survival (P = 0.002 and P < 0.001). We also found that KIAA0101 silencing decreased kidney cancer cell migration and invasion in vitro. CONCLUSIONS: Using an integrative system biology approach, we identified 3 novel factors as potential biomarkers (AHR, GRHL2 and KIAA0101) involved in ccRCC pathogenesis and not linked to kidney cancer before. PMID- 25139458 TI - Phosphine-catalyzed annulations of 4,4-dicyano-2-methylenebut-3-enoates with maleimides and maleic anhydride. AB - A novel phosphine-catalyzed [4+1] annulation of maleimides with 4,4-dicyano-2 methylenebut-3-enoates has been developed to afford spirocyclic products, and the maleimides serves as C1 synthons. Moreover, a phosphine-catalyzed formal [3+2] annulation between 4,4-dicyano-2-methylenebut-3-enoates and maleic anhydride has been also achieved, and maleic anhydride behaved as a C3 synthon in the reaction, thus efficiently affording the functionalized cyclopentenones. A stable phosphinium-containing zwitterionic compound is the key reactive intermediate in both annulations and was successfully isolated. Plausible mechanisms have been proposed on the basis of control experiments and deuterium-labeling experiments. PMID- 25139459 TI - Synthesis and characterization of a novel second-order nonlinear optical chromophore based on a new julolidine donor. AB - A new chromophore HK containing the cis,cis-1,7-diethoxy-3-isopropyljulolidine group as a novel electron-donor, thiophene as a pi-conjugated bridge and a tricyanofuran (TCF) acceptor has been synthesized and systematically investigated in this paper. Its corresponding chromophore FTC using 4-(diethyl amino)benzyl as the electron donor group was also prepared for comparison. This is the first time that the cis,cis-1,7-diethoxy-3-isopropyljulolidine group was introduced into NLO materials. Density functional theory (DFT) was used to calculate the HOMO-LUMO energy gap and first-order hyperpolarizability (beta) of the new chromophore. The HOMO-LUMO gap was also investigated by cyclic voltammetry (CV). Upon using the cis,cis-1,7-diethoxy-3-isopropyljulolidine group as the donor, a reduced energy gap of 1.007 eV was obtained compared with chromophore FTC (DeltaE = 1.529 eV). The high molecular hyperpolarizability of the new chromophore can be effectively translated into large electro-optic (EO) coefficients (r33) in poled polymers. The doped films containing the new chromophore HK showed a value of 72 pm V(-1) at the concentration of 25 wt% at 1310 nm. This value is almost two times higher than the EO activity of the usually reported traditional (N,N-diethyl) aniline nonlinear optical (NLO) chromophore FTC. High r33 values indicated that the new julolidine donor can efficiently improve the electron-donating ability and reduce intermolecular electrostatic interactions, thus enhancing the macroscopic EO activity. These properties, together with good solubility, suggest the potential use of the new chromophore in advanced materials devices. PMID- 25139460 TI - Effect of ERK1/2 signaling pathway in electro-acupuncture mediated up-regulation of heme oxygenase-1 in lungs of rabbits with endotoxic shock. AB - BACKGROUND: The anti-oxidative and anti-inflammatory activities of electro acupuncture (EA), a traditional clinical method, are widely accepted, but its mechanisms are not yet well defined. In this study, we investigated the role of extracellular signal-regulated kinases1/2 (ERK1/2) pathways on electro acupuncture - mediated up-regulation of heme oxygenase-1 (HO-1) in rabbit lungs injured by LPS-induced endotoxic shock. MATERIAL/METHODS: Seventy rabbits were randomly divided into 7 groups: group C, group M, group D, group SEAM, group EAM, group EAMPD, and group PD98059. Male New England white rabbits were given EA treatment on both sides once a day on days 1-5, and then received LPS to replicate the experimental model of injured lung induced by endotoxic shock. Then, they were killed by exsanguination at 6 h after LPS administration. The blood samples were collected for serum examination, and the lungs were removed for pathology examination, determination of wet-to-dry weight ratio, MDA content, SOD activity, serum tumor necrosis factor-alpha, determination of HO-1 protein and mRNA expression, and determination of ERK1/2 protein. RESULTS: The results revealed that after EA treatment, expression of HO-1and ERK1/2 was slightly increased compared to those in other groups, accompanied with less severe lung injury as indicated by lower index of lung injury score, lower wet-to-dry weight ratio, MDA content, and serum tumor necrosis factor-alpha levels, and greater SOD activity (p<0.05 for all). After pretreatment with ERK1/2 inhibitor PD98059, the effect of EA treatment and expression of HO-1 were suppressed (p<0.05 for all). CONCLUSIONS: After electro-acupuncture stimulation at ST36 and BL13, severe lung injury during endotoxic shock was attenuated. The mechanism may be through up regulation of HO-1, mediated by the signal transductions of ERK1/2 pathways. Thus, the regulation of ERK1/2 pathways via electro-acupuncture may be a therapeutic strategy for endotoxic shock. PMID- 25139462 TI - Novel strategies for preventing diabetes and obesity complications with natural polyphenols. AB - During the last years, the list of resveratrol effects has grown in parallel with the number of other members of the polyphenol family described to modulate glucose or lipid handling. In the same time, more than ten human studies on the influence of resveratrol supplementation on two related metabolic diseases, obesity and diabetes, have indicated that impressive beneficial effects co-exist with lack of demonstration of clinical relevance, irrespective of the daily dose ingested (0.075 to 1.5 g per capita) or the number of studied patients. Such contrasting observations have been proposed to depend on the degree of insulin resistance of the patients incorporated in the study. To date, no definitive conclusion can be drawn on the antidiabetic or antiobesity benefits of resveratrol. On the opposite, studies on animal models of diabesity consistently indicated that resveratrol impairs diverse insulin actions in adipocytes, blunting glucose transport, lipogenesis and adipogenesis. Since resveratrol also favours lipolysis and limits the production of proinflammatory adipokines, its administration in rodents results in limitation of fat deposition, activation of hexose uptake into muscle, improvement of insulin sensitivity, and facilitation of glucose disposal. Facing to a somewhat disappointing extrapolation to man of these promising antidiabetic and antiobesity properties, attention must be paid to re-examine resveratrol targets, especially those attainable after polyphenol ingestion and to re-define the responses to low doses. In this context, human adipocytes are proposed as a convenient model for the screening of "novel" polyphenols that can reproduce, out class, or reinforce resveratrol metabolic actions, Moreover, the use of combination of polyphenols is proposed to treat diabesity complications in view of recently reported synergisms. Lastly, multidisciplinar approaches are recommended for future investigations, considering the wide range of polyphenol actions that induce body fat reduction, liver disease mitigation, muscle function improvement, cardiovascular and renal protection. PMID- 25139461 TI - Telocytes subtypes in human urinary bladder. AB - Urinary bladder voiding is a complex mechanism depending upon interplay among detrusor, urothelium, sensory and motor neurons and connective tissue cells. The identity of some of the latter cells is still controversial. We presently attempted to clarify their phenotype(s) in the human urinary bladder by transmission electron microscopy (TEM) and immunohistochemistry. At this latter aim, we used CD34, PDGFRalpha, alphaSMA, c-Kit and calreticulin antibodies. Both, TEM and immunohistochemistry, showed cells that, sharing several telocyte (TC) characteristics, we identified as TC; these cells, however, differed from each other in some ultrastructural features and immunolabelling according to their location. PDGFRalpha/calret-positive, CD34/c-Kit-negative TC were located in the sub-urothelium and distinct in two subtypes whether, similarly to myofibroblasts, they were alphaSMA-positive and had attachment plaques. The sub-urothelial TC formed a mixed network with myofibroblasts and were close to numerous nerve endings, many of which nNOS-positive. A third TC subtype, PDGFRalpha/alphaSMA/c Kit-negative, CD34/calret-positive, ultrastructurally typical, was located in the submucosa and detrusor. Briefly, in the human bladder, we found three TC subtypes. Each subtype likely forms a network building a 3-D scaffold able to follow the bladder wall distension and relaxation and avoiding anomalous wall deformation. The TC located in the sub-urothelium, a region considered a sort of sensory system for the micturition reflex, as forming a network with myofibroblasts, possessing specialized junctions with extracellular matrix and being close to nerve endings, might have a role in bladder reflexes. In conclusions, the urinary bladder contains peculiar TC able to adapt their morphology to the organ activity. PMID- 25139463 TI - Return to football and long-term clinical outcomes after thumb ulnar collateral ligament suture anchor repair in collegiate athletes. AB - PURPOSE: To evaluate return to play after complete thumb ulnar collateral ligament (UCL) injury treated with suture anchor repair for both skill position and non-skill position collegiate football athletes and report minimum 2-year clinical outcomes in this population. METHODS: For this retrospective study, inclusion criteria were complete rupture of the thumb UCL and suture anchor repair in a collegiate football athlete performed by a single surgeon who used an identical technique for all patients. Data collection included chart review, determination of return to play, and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) outcomes. RESULTS: A total of 18 collegiate football athletes were identified, all of whom were evaluated for follow-up by telephone, e-mail, or regular mail at an average 6-year follow-up. Nine were skill position players; the remaining 9 played in nonskill positions. All players returned to at least the same level of play. The average QuickDASH score for the entire cohort was 1 out of 100; QuickDASH work score, 0 out of 100; and sport score, 1 out of 100. Average time to surgery for skill position players was 12 days compared with 43 for non-skill position players. Average return to play for skill position players was 7 weeks postoperatively compared with 4 weeks for non-skill position players. There was no difference in average QuickDASH overall scores or subgroup scores between cohorts. CONCLUSIONS: Collegiate football athletes treated for thumb UCL injuries with suture anchor repair had quick return to play, reliable return to the same level of activity, and excellent long-term clinical outcomes. Skill position players had surgery sooner after injury and returned to play later than non-skill position players, with no differences in final level of play or clinical outcomes. Management of thumb UCL injuries in collegiate football athletes can be safely and effectively tailored according to the demands of the player's football position. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 25139464 TI - Constrained postures and spatial S-R compatibility as measured by the Simon effect. AB - Whereas working under constrained postures is known to influence the worker's perceived comfort and health, little is known in regard to its influence on performance. Employing an Auditory Simon task while varying posture, we investigated the relationship between constrained postures and cognitive processes in three experiments. In Experiment 1 and 2, participants operated a rocker switch or a control knob with one hand either in front or in the back of their body and while either sitting or kneeling. Perceived musculoskeletal exertion was gathered with a questionnaire. Results of the first two experiments showed differently perceived comfort and a minor effect of constrained posture on cognitive performance. However, results indicated that spatial coding in the back compares to either a virtual turn of the observer towards the control device (front-device coding) or along the observer's hand (effector coding). To clarify this issue the rocker switch was operated with one or two hands in Experiment 3, showing a comparable coding only in the one-hand condition and indicating evidence for the effector-coding hypothesis in the back. PMID- 25139465 TI - Percutaneous Coronary Intervention in Spontaneous Coronary Artery Dissection: Role of Intravascular Ultrasound. AB - Spontaneous coronary artery dissection (SCAD) is a rare, life-threatening condition that usually manifests as an acute myocardial infarction. Diagnosing SCAD with conventional coronary angiogram can be challenging, particularly if the true lumen is severely narrowed. Our case highlights the challenges in performing successful percutaneous coronary intervention (PCI) in patients with SCAD. Intravascular ultrasound can prove to be a pivotal tool in the diagnosis and successful management of such cases by establishing the anatomic site of dissection, and confirming stent placement in the true lumen following PCI. PMID- 25139466 TI - Os(II) phosphors with near-infrared emission induced by ligand-to-ligand charge transfer transition. AB - Heating of Os3(CO)12 with 6 equiv of 2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5 yl) pyridine (fptzH) in refluxing diethylene glycol monomethyl ether, followed by sequential treatment with stoichiometric Me3NO and addition of PPhMe2, afforded two isomeric mixtures of red-emitting [Os(fptz)2(PPhMe2)2] (1T and 1C), for which the notations T and C stand for the trans and cis-oriented fptz chelates, respectively. Alternatively, preparation of Os(II) complex using a 1:1 mixture of 5,5'-di(trifluoromethyl)-3,3'-di-1,2,4-triazole (dttzH2) and 2,2'-bipyridine (bpy), instead of fptzH, gave isolation of a mononuclear Os(II) complex [Os(bpy)(dttz)(CO)2] (2) in moderate yield. Replacement of CO with PPhMe2 on 2 afforded near-infrared (NIR)-emitting Os(II) complex [Os(bpy)(dttz)(PPhMe2)2] (3). The single-crystal X-ray structural analyses were executed on 1C, 2, and 3 to reveal the structural influence imposed by the various chelates. The photophysical and electrochemical properties were measured and discussed using the results of density functional theory (DFT) and time-dependent DFT calculations. Complex 3 is selected as the dopant to probe its electroluminescent properties by fabrication of the NIR emitting organic light-emitting diodes. PMID- 25139467 TI - Single-item measures for depression and anxiety: Validation of the Screening Tool for Psychological Distress in an inpatient cardiology setting. AB - BACKGROUND: Depression and anxiety are common among patients with cardiovascular disease (CVD) and confer significant cardiac risk, contributing to CVD morbidity and mortality. Unfortunately, due to the lack of screening tools that address the specific needs of hospitalized patients, few cardiac inpatient programs offer routine screening for these forms of psychological distress, despite recommendations to do so. AIMS: The purpose of this study was to validate single item measures for depression and anxiety among cardiac inpatients. METHODS: Consecutive inpatients were recruited from the cardiology and cardiac surgery step-down units at a university-affiliated, quaternary-care hospital. Subjects completed a questionnaire that included: (a) demographics, (b) single-item measures for depression and anxiety (from the Screening Tool for Psychological Distress (STOP-D)), and (c) Hospital Anxiety and Depression Scale (HADS). RESULTS: One hundred and five participants were recruited with a wide variety of cardiac diagnoses, having a mean age of 66 years, and 28% were women. Both STOP-D items were highly correlated with their corresponding validated measures and demonstrated robust receiver-operator characteristic curves. Severity scores on both items correlated well with established severity cut-off scores on the corresponding subscales of the HADS. CONCLUSIONS: The STOP-D is a self administered, self-report measure using two independent items that provide severity scores for depression and anxiety. The tool performs very well compared with other previously validated measures. Requiring no additional scoring and being free, STOP-D offers a simple and valid method for identifying hospitalized cardiac patients who are experiencing psychological distress. This crucial first step triggers initiation of appropriate monitoring and intervention, thus reducing the likelihood of the adverse cardiac outcomes associated with psychological distress. PMID- 25139468 TI - The importance of interactions between patients and healthcare professionals for heart failure self-care: A systematic review of qualitative research into patient perspectives. AB - BACKGROUND: Effective heart failure (HF) self-care can improve clinical outcomes but is dependent on patients' undertaking a number of complex self-care behaviors. Research into the effectiveness of HF management programs demonstrates mixed results. There is a need to improve understanding of patient perspectives' of self-care need in order to enhance supportive interventions. AIM: This paper reports selected findings from a systematic review of qualitative research related to HF self-care need from the patients' perspective. The focus here is on those facets of patient-healthcare professional relationships perceived by patients to influence HF self-care. METHOD: We searched multiple healthcare databases to identify studies reporting qualitative findings with extractable data related to HF self-care need. Joanna Briggs Institute systematic review methods were employed and recognized meta-synthesis techniques were applied. Critical realist theory provided analytical direction to highlight how individual and contextual factors came together in complex ways to influence behavior and outcomes. RESULTS: Altogether 24 studies (1999-2012) containing data on patient healthcare professional relationships and HF self-care were included. Interaction with healthcare professionals influenced self-care strongly but was notably mixed in terms of reported quality. Effective HF self-care was more evident when patients perceived that their healthcare professional was responsive, interested in their individual needs, and shared information. Poor communication and lack of continuity presented common barriers to HF self-care. CONCLUSION: Interactions and relationships with clinicians play a substantial role in patients' capacity for HF self-care. The way healthcare professionals interact with patients strongly influences patients' understanding about their condition and self-care behaviors. PMID- 25139469 TI - Covariate measurement error correction methods in mediation analysis with failure time data. AB - Mediation analysis is important for understanding the mechanisms whereby one variable causes changes in another. Measurement error could obscure the ability of the potential mediator to explain such changes. This article focuses on developing correction methods for measurement error in the mediator with failure time outcomes. We consider a broad definition of measurement error, including technical error, and error associated with temporal variation. The underlying model with the "true" mediator is assumed to be of the Cox proportional hazards model form. The induced hazard ratio for the observed mediator no longer has a simple form independent of the baseline hazard function, due to the conditioning event. We propose a mean-variance regression calibration approach and a follow-up time regression calibration approach, to approximate the partial likelihood for the induced hazard function. Both methods demonstrate value in assessing mediation effects in simulation studies. These methods are generalized to multiple biomarkers and to both case-cohort and nested case-control sampling designs. We apply these correction methods to the Women's Health Initiative hormone therapy trials to understand the mediation effect of several serum sex hormone measures on the relationship between postmenopausal hormone therapy and breast cancer risk. PMID- 25139470 TI - Utilization of Zwitterion-based solutions to dissect the relative effects of solution pH and ionic strength on the aggregation behavior and conformational stability of a fusion protein. AB - Solution pH and ionic strength (I) have complex effects on protein stability. We developed an experimental approach based on exploitation of the zwitterionic characteristic of amino acid molecules to probe the relative contribution from each. A variety of types of amino acid solutions were adopted to investigate the effects of pH and I in a manner that allows independent evaluation of each factor. The same effect could not be achieved using conventional buffer solutions. Size-exclusion chromatography, capillary differential scanning calorimetry, and fluorescence spectroscopy were utilized to probe the protein aggregation and conformation. The results suggested that, in addition to pH, solution ionic strength as a function of ionization state of the amino acid molecules and the ions introduced by pH adjustment played an important role in the aggregation and conformation of the protein studied. This experimental approach offers a useful tool to aid fundamental understanding of the relative effects of solution pH and ionic strength on protein stability. PMID- 25139471 TI - Using (18)F-FLT PET to distinguish between malignant and benign breast lesions with suspicious findings in mammography and breast ultrasound. AB - PURPOSE: To investigate the diagnostic performance of 3'-deoxy-3' [(18)F]fluorothymidine ((18)F-FLT) PET in women with suspicious breast findings on conventional imaging (mammography and breast ultrasound). METHODS: Twenty eight women with suspicious findings on conventional imaging were enrolled. A whole-body PET/CT in the supine position (first PET) was performed 60 min after intravenous injection of 0.07 mCi/kg (18)F-FLT, followed by a regional PET of the breast in the prone position (second PET). For each lesion, the SUVmax of the first PET (SUV1) and second PET (SUV2) were measured. For the receiver operating characteristic (ROC) analysis of the diagnostic parameters, of the cutoff points with sensitivities >90 %, we chose the one with highest specificity as the optimal cutoff point to obtain the corresponding sensitivity and specificity. RESULTS: A total of 34 breast lesions (21 benign, 13 malignant) were analyzed. The SUV1 and SUV2 of the malignant lesions (median values 4.6 vs. 4.4, respectively) were higher than those of the benign lesions that had medians of 1.2 and 1.0, respectively (P = 0.0001). The area under the ROC curve (AUC) of SUV1 (0.905) showed no significant difference from that of SUV2 (0.912) (P = 0.77). The sensitivity and specificity using SUV1 = 1.24 as cutoff were 92.3 and 52.4 %, and those using SUV2 = 1.5 as cutoff were 92.3 and 66.7 %, respectively. CONCLUSION: (18)F-FLT PET showed acceptable diagnostic performance for suspicious breast findings on conventional imaging, and SUV2 showed higher specificity than SUV1. PMID- 25139472 TI - 68Gallium- and 90Yttrium-/ 177Lutetium: "theranostic twins" for diagnosis and treatment of NETs. AB - Abundant expression of somatostatin receptors (SSTR) is frequently identified in differentiated neuroendocrine tumors and may serve as potential target for diagnostic imaging and treatment. This article discusses the "theranostic approach" of SSTR-targeting compounds including an overview of its role for diagnosis, staging and restaging, discussing its way to being established in clinical routine, and giving an outlook about further potentially relevant developments. PMID- 25139473 TI - Glucose control and diabetic neuropathy: lessons from recent large clinical trials. AB - Diabetic peripheral and autonomic neuropathies are common complications of diabetes with broad spectrums of clinical manifestations and high morbidity. Studies using various agents to target the pathways implicated in the development and progression of diabetic neuropathy were promising in animal models. In humans, however, randomized controlled studies have failed to show efficacy on objective measures of neuropathy. The complex anatomy of the peripheral and autonomic nervous systems, the multitude of pathogenic mechanisms involved, and the lack of uniformity of neuropathy measures have likely contributed to these failures. To date, tight glycemic control is the only strategy convincingly shown to prevent or delay the development of neuropathy in patients with type 1 diabetes and to slow the progression of neuropathy in some patients with type 2 diabetes. Lessons learned about the role of glycemic control on distal symmetrical polyneuropathy and cardiovascular autonomic neuropathy are discussed in this review. PMID- 25139474 TI - Lossless data compression for improving the performance of a GPU-based beamformer. AB - The powerful parallel computation ability of a graphics processing unit (GPU) makes it feasible to perform dynamic receive beamforming However, a real time GPU based beamformer requires high data rate to transfer radio-frequency (RF) data from hardware to software memory, as well as from central processing unit (CPU) to GPU memory. There are data compression methods (e.g. Joint Photographic Experts Group (JPEG)) available for the hardware front end to reduce data size, alleviating the data transfer requirement of the hardware interface. Nevertheless, the required decoding time may even be larger than the transmission time of its original data, in turn degrading the overall performance of the GPU based beamformer. This article proposes and implements a lossless compression decompression algorithm, which enables in parallel compression and decompression of data. By this means, the data transfer requirement of hardware interface and the transmission time of CPU to GPU data transfers are reduced, without sacrificing image quality. In simulation results, the compression ratio reached around 1.7. The encoder design of our lossless compression approach requires low hardware resources and reasonable latency in a field programmable gate array. In addition, the transmission time of transferring data from CPU to GPU with the parallel decoding process improved by threefold, as compared with transferring original uncompressed data. These results show that our proposed lossless compression plus parallel decoder approach not only mitigate the transmission bandwidth requirement to transfer data from hardware front end to software system but also reduce the transmission time for CPU to GPU data transfer. PMID- 25139475 TI - Lipopolysaccharide-induced sickness behavior in lactating rats decreases ultrasonic vocalizations and exacerbates immune system activity in male offspring. AB - OBJECTIVE: The present study analyzed the effects of lipopolysaccharide (LPS) on maternal behavior during lactation and possible correlations with changes in emotional and immune responses in offspring. METHODS: Lactating rats received 100 MUg/kg LPS, and the control group received saline solution on lactation day (LD) 3. Maternal general activity and maternal behavior were observed on LD5 (i.e. the day that the peak of fever occurred). In male pups, hematological parameters and ultrasonic vocalizations (USVs) were assessed on LD5. At weaning, an additional dose of LPS (50 ug/kg, i.p.) was administered in male pups, and open-field behavior, oxidative burst and phagocytosis were evaluated. RESULTS: A reduction in the time in which dams retrieved the pups was observed, whereas no effects on maternal aggressive behavior were found. On LD5, a reduction of the frequency of USVs was observed in pups, but no signs of inflammation were found. At weaning, an increase in immune system activity was observed, but no differences in open field behavior were found. CONCLUSION: These results indicate that inflammation in lactating mothers disrupted mother/pup interactions and may have produced short- and long-term effects on pup behavior as well as biological pathways that modulate inflammatory responses to bacterial endotoxin challenge in pups. PMID- 25139476 TI - Rescue balloon dilation of the ampulla for retrieving an impacted biliary extraction basket. PMID- 25139477 TI - Are perfluoroalkyl acids in waste water treatment plant effluents the result of primary emissions from the technosphere or of environmental recirculation? AB - Wastewater treatment plants (WWTP) have been suggested to be one of the major pathways of perfluoroalkyl acids (PFAAs) from the technosphere to the aquatic environment. The origin of PFAAs in WWTP influents is either from current primary emissions or a result of recirculation of PFAAs that have been residing and transported in the environment for several years or decades. Environmental recirculation can then occur when PFAAs from the environment enter the wastewater stream in, e.g., tap water. In this study 13 PFAAs and perfluorooctane sulfonamide were analyzed in tap water as well as WWTP influent, effluent and sludge from three Swedish cities: Bromma (in the metropolitan area of Stockholm), Bollebygd and Umea. A mass balance of the WWTPs was assembled for each PFAA. Positive mass balances were observed for PFHxA and PFOA in all WWTPs, indicating the presence of precursor compounds in the technosphere. With regard to environmental recirculation, tap water was an important source of PFAAs to the Bromma WWTP influent, contributing >40% for each quantified sulfonic acid and up to 30% for the carboxylic acids. The PFAAs in tap water from Bollebygd and Umea did not contribute significantly to the PFAA load in the WWTP influents. Our results show that in order to estimate current primary emissions from the technosphere, it may be necessary to correct the PFAA emission rates in WWTP effluents for PFAAs present in tap water, especially in the case of elevated levels in tap water. PMID- 25139478 TI - [Aneurysms of the thoracic and thoracoabdominal aorta]. AB - The incidence and operations of thoracic and thoracoabdominal aortic aneurysms have significantly increased. The indications for repair are considered to be a diameter of 6 cm or more and 5.5 cm for patient groups with increased risk of rupture. Complex open surgical repair is associated with significant mortality and complication rates. Total or hybrid endovascular repair seems to reduce early postoperative complications and mortality. The endovascular approach has evolved to be a good and predominant alternative to open repair of these aneurysms for older and high-risk patients as well as for aneurysms with optimal morphological suitability. Notwithstanding, at present a complete paradigm shift from open to endovascular repair for all patients, especially those with complex aneurysms, cannot yet be established. PMID- 25139479 TI - [Transvaginal cholecystectomy: results of a randomized study]. AB - BACKGROUND: Transvaginal cholecystectomy (TVC) is regarded as a model operation in the newly developed field of natural orifice transluminal endoscopic surgery (NOTES). Randomized, controlled trials to assess TVC as a surgical strategy are largely missing. MATERIALS AND METHODS: The study was a double blind, randomized, controlled, single center trial in female patients > 18 years with symptomatic cholecystolithiasis comparing laparoscopic cholecystectomy (CLC) and TVC. The study investigated pain reduction of >= 1 point on a visual-numeric rating scale with a follow-up after 7 days. Secondary endpoints were complications and patient reported outcome. Groups were established using computer-generated randomization and sealed envelopes in the operating theatre. At the end of the surgical procedure all patients received a standard 4-trocar dressing as for CLC and a vaginal tamponade. RESULTS: A total of 426 patients were asked to participate, of which 97 were randomized, 51 in the CLC, 41 in the TVC groups and 5 were excluded from the study. Patients were comparable regarding age, body mass index (BMI) and American Society of Anesthesiologists (ASA) grade. Surgical and anesthesia times were significantly different. There was no difference in postoperative pain. The majority of patients were satisfied with both procedures and TVC was recommended to other patients by 93 % of patients in the TVC group. CONCLUSION: The results did not show superiority of TVC over CLC with regards to postoperative pain. With no differences in postoperative pain and high patient satisfaction, TVC can be recommended to future patients as an alternative method. For confirmation of this evaluation of TVC further randomized trials are needed. PMID- 25139481 TI - Regulation of insulin on lipid metabolism in freshly isolated hepatocytes from yellow catfish (Pelteobagrus fulvidraco). AB - Although the metabolic actions of insulin in fish have been investigated widely in the past years, the regulatory effect of insulin on lipid metabolism has received little attention, especially in primary hepatocytes of fish. In the present study, freshly hepatocytes were isolated from yellow catfish, cultured and subjected to different insulin levels (0, 10, 100 and 1000nM) for 0h, 24h and 48h. Triglyceride (TG) content, activity and expression of several key enzymes involved in lipid metabolism, as well as mRNA levels of key transcription factors related to lipid metabolism, were assessed at 0h, 24h and 48h, respectively. Insulin incubation tended to increase the activities and expression of several lipogenic enzymes (such as FAS, G6PD, 6PGD). However, reduced CPT I gene expression was observed in hepatocytes following incubation treatment. Insulin administration also tended to up-regulate SREBP-1 expression but down-regulate PPARalpha mRNA levels. Insulin incubation enhanced lipogenesis and reduced lipolysis of freshly isolated hepatocytes of yellow catfish, in coincidence with increased TG content. Pearson correlations between expression of SREBP-1 and PPARalpha, and expression and activity of several enzymes were also observed, especially at 48-h insulin incubation. To the best of our knowledge, this is the first to study the effects of insulin on lipogenesis and lipolysis at both transcriptional and enzymatic levels using primary hepatocytes culture model in fish, which will help to understand the regulation of lipid metabolism by insulin in vivo, and will give us new insight into the insulin role in nutrient metabolism in fish. PMID- 25139482 TI - The strong relation between post-hemodialysis blood methylglyoxal levels and post hemodialysis blood glucose concentration rise. AB - BACKGROUND: Hemodialysis is known to decrease blood glucose concentration (BGC), insulin, and methylglyoxal levels. However, the effects of decreases in these factors on the increase in post-hemodialysis BGC remain unknown. This study identifies the effects of hemodialysis-induced changes in concentrations of these elements on post-hemodialysis BGC. METHODS: Study subjects included seventeen insulin-treated diabetes patients receiving hemodialysis. The fluctuations in BGC on hemodialysis-treatment days and non-hemodialysis-treatment days were evaluated using a continuous glucose monitoring system. BGC was evaluated before breakfast, before starting hemodialysis, at the end of hemodialysis, 1 h post-hemodialysis (lunch), and 6 h post-hemodialysis (dinner). BGC, insulin, and methylglyoxal levels were measured at the start and end of hemodialysis. This study also evaluated the changes in the concentrations of glucose and insulin in the arterial line and the venous line during hemodialysis. RESULTS: Hemodialysis decreases BGC, insulin, and methylglyoxal levels. Concentrations of glucose and insulin in the arterial line gradually decreased during dialysis, while concentrations in the venous line approached their original concentrations in the dialysis solution. BGC rose sharply after eating lunch 1 h post-hemodialysis. The blood glucose, insulin, and methylglyoxal concentrations at the end of hemodialysis were associated with the M values and the mean amplitude of glycemic excursion values between before lunch and dinner. In particular, methylglyoxal concentration at the end of hemodialysis was strongly related to the post hemodialysis increase in BGC. CONCLUSION: Hemodialysis-induced decreases in methylglyoxal concentrations and methylglyoxal concentration at the end of hemodialysis influence post-hemodialysis fluctuations in BGC. PMID- 25139483 TI - Early life seizures in female rats lead to anxiety-related behavior and abnormal social behavior characterized by reduced motivation to novelty and deficit in social discrimination. AB - Previously, we demonstrated that male Wistar rats submitted to neonatal status epilepticus showed abnormal social behavior characterized by deficit in social discrimination and enhanced emotionality. Taking into account that early insult can produce different biological manifestations in a gender-dependent manner, we aimed to investigate the social behavior and anxiety-like behavior in female Wistar rats following early life seizures. Neonate female Wistar rats at 9 days postnatal were subject to pilocarpine-induced status epilepticus and the control received saline. Behavioral tests started from 60 days postnatal and were carried out only during the diestrus phase of the reproductive cycle. In sociability test experimental animals exhibited reduced motivation for social encounter and deficit in social discrimination. In open field and the elevated plus maze, experimental animals showed enhanced emotionality with no changes in basal locomotor activity. The results showed that female rats submitted to neonatal status epipepticus showed impaired social behavior, characterized by reduced motivation to novelty and deficit in social discrimination in addition to enhanced emotionality. PMID- 25139484 TI - Exposure to static and time-varying magnetic fields from working in the static magnetic stray fields of MRI scanners: a comprehensive survey in the Netherlands. AB - Clinical and research staff who work around magnetic resonance imaging (MRI) scanners are exposed to the static magnetic stray fields of these scanners. Although the past decade has seen strong developments in the assessment of occupational exposure to electromagnetic fields from MRI scanners, there is insufficient insight into the exposure variability that characterizes routine MRI work practice. However, this is an essential component of risk assessment and epidemiological studies. This paper describes the results of a measurement survey of shift-based personal exposure to static magnetic fields (SMF) (B) and motion induced time-varying magnetic fields (dB/dt) among workers at 15 MRI facilities in the Netherlands. With the use of portable magnetic field dosimeters, >400 full shift and partial shift exposure measurements were collected among various jobs involved in clinical and research MRI. Various full-shift exposure metrics for B and motion-induced dB/dt exposure were calculated from the measurements, including instantaneous peak exposure and time-weighted average (TWA) exposures. We found strong correlations between levels of static (B) and time-varying (dB/dt) exposure (r = 0.88-0.92) and between different metrics (i.e. peak exposure, TWA exposure) to express full-shift exposure (r = 0.69-0.78). On average, participants were exposed to MRI-related SMFs during only 3.7% of their work shift. Average and peak B and dB/dt exposure levels during the work inside the MRI scanner room were highest among technical staff, research staff, and radiographers. Average and peak B exposure levels were lowest among cleaners, while dB/dt levels were lowest among anaesthesiology staff. Although modest exposure variability between workplaces and occupations was observed, variation between individuals of the same occupation was substantial, especially among research staff. This relatively large variability between workers with the same job suggests that exposure classification based solely on job title may not be an optimal grouping strategy for epidemiological purposes. PMID- 25139485 TI - Single-nucleotide polymorphisms in the vascular endothelial growth factor pathway and outcomes of patients treated with first-line cytotoxic chemotherapy combined with bevacizumab for advanced colorectal cancer. AB - OBJECTIVE: The aim of this study was to evaluate the association between the efficacy of first-line cytotoxic chemotherapy plus bevacizumab and single nucleotide polymorphisms (SNPs) of angiogenic genes in patients with advanced colorectal cancer (CRC). METHODS: DNA was extracted from blood samples of 125 patients, and 12 SNPs were evaluated for association with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: The vascular endothelial growth factor A (VEGFA) rs833061 T/T was associated with superior ORR compared to its alternative genotypes (75.9 vs. 50.8%; p = 0.008), and the interleukin 8 rs4073 A/A genotype tended to be associated with poor ORR (45.0 vs. 66.0%; p = 0.067). The median PFS and OS were superior in patients with the fms-related tyrosine kinase 1 (FLT1) rs9513070 A/A genotype (8.7 vs. 6.6 months; p = 0.001 and 26.4 vs. 16.1 months; p = 0.038, respectively). The kinase insert domain receptor rs1531289 G/G genotype tended to be associated with improved PFS (8.0 vs. 7.1 months; p = 0.069). In haplotype analysis, the FLT1 rs9513070/rs9554320/rs9582036 GCA haplotype was associated with inferior PFS and OS (p = 0.004 and p = 0.041, respectively). CONCLUSION: The VEGFA rs833061 SNP is associated with the ORR, and the FLT1 rs9513070 SNP and FLT1 GCA haplotypes are associated with PFS and OS in advanced CRC patients treated with cytotoxic chemotherapy plus bevacizumab. PMID- 25139486 TI - Stroke care continues to show "unacceptable variation," audit finds. PMID- 25139487 TI - Systemic exposure of topical erythromycin in comparison to oral administration and the effect on cytochrome P450 3A4 activity. AB - AIMS: Erythromycin is a macrolide antibiotic, which is frequently used as a topical formulation for the treatment of acne. It is also known as an inhibitor of the cytochrome P450 (CYP) isoenzyme 3A4. In this study, the systemic availability of topical erythromycin, hence the influence on the activity of CYP3A, is evaluated in comparison to orally administered erythromycin. METHODS: Sixteen healthy volunteers received consecutively topical (two applications of 800 mg) and oral erythromycin (two dose groups, 250 and 1000 mg, with n = 8) to assess erythromycin pharmacokinetics. A microdose of midazolam (3 MUg orally) was used to determine the effect on CYP3A activity. RESULTS: After topical administration, erythromycin was detected in the plasma of every participant without causing a statistically significant alteration of CYP3A activity. After oral administration, the dose-normalized erythromycin exposure (AUCinfinity ) was 1335 h ng ml(-1) after 250 mg and 3-fold higher after the 1000 mg dose (4051 h ng ml(-1); P < 0.01), suggesting nonlinear pharmacokinetics of erythromycin. Both oral doses inhibited CYP3A activity; midazolam clearance was decreased to 61% (250 mg) and 21% (1000 mg). The relationship between erythromycin exposure and CYP3A activity (Hill equation) revealed a 50% reduction of CYP3A activity by an erythromycin AUCinfinity of 2106 h ng ml(-1). CONCLUSIONS: Topical erythromycin did not cause clinically relevant CYP3A alterations, although low systemic availability of erythromycin was observed. This supports the assumption that treatment with topical erythromycin is not critical in terms of CYP3A inhibition. Furthermore, substantial nonlinearity of erythromycin pharmacokinetics after two different oral doses was observed, possibly due to autoinhibition. PMID- 25139488 TI - What are the pharmacotherapy options for treating prediabetes? AB - INTRODUCTION: The incidence of type 2 diabetes mellitus (T2DM) has risen to epidemic proportions, and this is associated with enormous cost. T2DM is preceded by 'prediabetes', and the diagnosis of impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) provides an opportunity for targeted intervention. Prediabetic subjects manifest both core defects characteristic of T2DM, that is, insulin resistance and beta-cell dysfunction. Interventions which improve insulin sensitivity and/or preserve beta-cell function are logical strategies to delay the conversion of IGT/IFG to T2DM or revert glucose tolerance to normal. AREAS COVERED: The authors examine pharmacologic agents that have proven to decrease the conversion of IGT to T2DM and represent potential treatment options in prediabetes. EXPERT OPINION: Weight loss improves whole body insulin sensitivity, preserves beta-cell function and decreases progression of prediabetes to T2DM. In real life long-term weight loss is the exception and, even if successful, 40 - 50% of IGT individuals still progress to T2DM. Pharmacotherapy provides an alternative strategy to improve insulin sensitivity and preserve beta-cell function. Thiazolidinediones (TZDs) are highly effective in T2DM prevention. Long acting glucagon-like peptide-1 (GLP-1) analogs, because they augment beta-cell function and promote weight loss, are effective in preventing IGT progression to T2DM. Metformin is considerably less effective than TZDs or GLP-1 analogs. PMID- 25139489 TI - Cellular distribution of Egr1 transcription in the male rat pituitary gland. AB - The transcription factor gene Egr1 is necessary for female fertility; EGR1 protein is an established molecular regulator of adult female gonadotroph function where it mediates GNRH-stimulated transcription of the Lhb gene. Recent studies have also implicated pituitary EGR1 in the mediation of other physiological signals indicating an integrative function. However, the role of EGR1 in males is less well defined and this uncertainty is compounded by the absence of cellular expression data in the male pituitary gland. The aim of this study, therefore, was to define the distribution of Egr1 gene expression in the adult male rat pituitary. To further this aim, we have evaluated cellular populations in a transgenic rat model (Egr1-d2EGFP), in which we demonstrate regulated green fluorescent protein (GFP) expression in EGR1+ pituitary cells. Cellular filling by GFP enabled morphological and molecular differentiation of different populations of gonadotrophs; Egr1 transcription and LHB were highly co localised in a major population of large cells but only minimally co-localised in small GFP+ cells; the latter cells were shown to be largely (80%) composed of minority populations of GH+ somatotrophs (9% of total GH+) and PRL+ lactotrophs (3% of total PRL+). Egr1 transcription was not found in TSH+, ACTH+ or SOX2+ precursor cells and was only minimally co-localised in S-100beta+ folliculostellate cells. Our demonstration that the Egr1 gene is actively and selectively transcribed in a major sub-population of male LHB+ cells indicates a largely conserved role in gonadotroph function and has provided a basis for further defining this role. PMID- 25139490 TI - 1,25-Vitamin D3 promotes cardiac differentiation through modulation of the WNT signaling pathway. AB - Cardiovascular disease (CVD) remains the leading cause of death worldwide. Low levels of vitamin D are associated with high risk of myocardial infarction, even after controlling for factors associated with coronary artery disease. A growing body of evidence indicates that vitamin D plays an important role in CVD-related signaling pathways. However, little is known about the molecular mechanism by which vitamin D modulates heart development. The WNT signaling pathway plays a pivotal role in tissue development by controlling stem cell renewal, lineage selection and, even more importantly, heart development. In this study, we examined the role of 1,25-D3 (the active form of vitamin D) on cardiomyocyte proliferation, apoptosis, cell phenotype, cell cycle progression and differentiation into cardiomyotubes. We determined that the addition of 1,25-D3 to cardiomyocytes cells: i) inhibits cell proliferation without promoting apoptosis; ii) decreases expression of genes related to the regulation of the cell cycle; iii) promotes formation of cardiomyotubes; iv) induces the expression of casein kinase-1-alpha1, a negative regulator of the canonical WNT signaling pathway; and v) increases the expression of the noncanonical WNT11, which it has been demonstrated to induce cardiac differentiation during embryonic development and in adult cells. In conclusion, we postulate that vitamin D promotes cardiac differentiation through a negative modulation of the canonical WNT signaling pathway and by upregulating the expression of WNT11. These results indicate that vitamin D repletion to prevent and/or improve cardiovascular disorders that are linked with abnormal cardiac differentiation, such as post infarction cardiac remodeling, deserve further study. PMID- 25139491 TI - Damnacanthal inhibits the NF-kappaB/RIP-2/caspase-1 signal pathway by inhibiting p56lck tyrosine kinase. AB - Damnacanthal is a major constituent of Morinda citrifolia L. (noni) and exhibits anti-cancer and anti-inflammatory activities. However, the effects of damnacanthal on allergic diseases have not been determined. In this study, we investigated the effect of damnacanthal on mast cell-mediated allergic inflammatory responses. Damnacanthal significantly and dose-dependently inhibited compound 48/80-induced systemic anaphylactic shock, histamine release and intracellular calcium levels. In particular, IgE-mediated passive cutaneous anaphylaxis was significantly inhibited by the oral administration of damnacanthal. In addition, we report for the first time that p56lck tyrosine kinase was expressed in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated mast cells. Furthermore, damnacanthal inhibited the up regulation of p56lck tyrosine kinase activity by PMACI and repressed PMACI induced histidine decarboxylase expression and activity. Damnacanthal also inhibited PMACI-induced interleukin (IL)-1beta, IL-6 and tumor necrosis factor alpha expressions by suppressing nuclear factor-kappa B (NF-kappaB) activation and suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. This study shows damnacanthal inhibits the NF kappaB/receptor-interacting protein-2/caspase-1 signal pathway by inhibiting p56lck tyrosine kinase and suggests that damnacanthal has potential for the treatment of mast cell-mediated allergic disorders. PMID- 25139492 TI - Monitoring the response of bone metastases to treatment with Magnetic Resonance Imaging and nuclear medicine techniques: a review and position statement by the European Organisation for Research and Treatment of Cancer imaging group. AB - Assessment of the response to treatment of metastases is crucial in daily oncological practice and clinical trials. For soft tissue metastases, this is done using computed tomography (CT), Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET) using validated response evaluation criteria. Bone metastases, which frequently represent the only site of metastases, are an exception in response assessment systems, because of the nature of the fixed bony defects, their complexity, which ranges from sclerotic to osteolytic and because of the lack of sensitivity, specificity and spatial resolution of the previously available bone imaging methods, mainly bone scintigraphy. Techniques such as MRI and PET are able to detect the early infiltration of the bone marrow by cancer, and to quantify this infiltration using morphologic images, quantitative parameters and functional approaches. This paper highlights the most recent developments of MRI and PET, showing how they enable early detection of bone lesions and monitoring of their response. It reviews current knowledge, puts the different techniques into perspective, in terms of indications, strengths, weaknesses and complementarity, and finally proposes recommendations for the choice of the most adequate imaging technique. PMID- 25139493 TI - Prenatal Diagnosis of Infantile Myofibroma with Postnatal Imaging Correlation. AB - Infantile myofibroma is the most common fibrous tumor in infancy. A majority of these lesions are solitary and occur in the head and neck region. Unless visceral sites are involved, the clinical course is typically benign. However, the difficulty in these cases is the differentiation of a benign myofibroma from a solitary malignant neoplasm and determination of visceral involvement. Prenatal diagnosis of this condition is rarely described in the literature, but it does indeed have a role in perinatal management. Our patient was initially identified by prenatal ultrasound with fetal MRI for further characterization of the mass. We present the case of a prenatally diagnosed solitary infantile myofibroma of the lower extremity and highlight the role of prenatal imaging in the diagnosis and treatment of this condition. PMID- 25139494 TI - Glycogen phosphorylase BB in myocardial infarction. AB - Early experimental and clinical reports on glycogen phosphorylase BB (GPBB) kinetics following myocardial ischemic injury suggested that it could be a useful diagnostic marker for early detection of acute myocardial infarction (AMI). After more than two decades of investigation, there is now overwhelming body of evidence that do not support the use of GPBB measurement in diagnosis of acute AMI in patients presenting with acute chest pain. Currently, GPBB cannot be recommended as a diagnostic marker of AMI either as a stand-alone test or as an addition to (high-sensitive) troponin testing. It should be noted that these considerations apply to the early diagnosis of AMI, not to the prognostic stratification, which is also suggested but it warrants further investigation. The aim of this review is to summarize available evidence of GPBB measurement in early diagnosis of myocardial infarction. PMID- 25139495 TI - Intra-day and inter-day biological variations of peripheral blood lymphocytes. AB - BACKGROUND: The proportion and absolute numbers of lymphocyte subsets are important indices that reflect the immunological status of the body. Few studies on biological variations of absolute lymphocyte subset counts and no study in Asian population are currently available. Furthermore, there have been few reports on the biological variation of these indices in the short term. METHODS: At 8:00AM, 12:00PM, and 4:00PM on days 1, 3, and 5, venous blood was collected from 20 healthy volunteers. All participants maintained their normal lifestyles. The percent and absolute lymphocyte subset counts were measured using single platform method. RESULTS: Intraday and interday biological variations for the absolute and percent counts of lymphocyte subsets were relatively constant. The intra-individual coefficient of variation (CVI) and inter-individual coefficient of variation (CVG) were similar to those in previous studies. Biological variations in the percent and absolute counts for the CD3(+)CD4(-)CD8(-), CD3(+)CD4(+)CD8(+), and CD3(+)CD16(+)CD56(+) subsets were relatively high. CONCLUSIONS: These observations are clinically valuable. Investigation on the CVI and CVG may allow us to determine the utility of traditional population based reference ranges. Documentation of the reference change values may be used as objective delta-check values in quality management and decide whether the change that occur in an individual's serial results before the change is significant. The present study also enriched the database regarding the biological variations of lymphocyte subsets in Asian population. PMID- 25139496 TI - Serum levels of soluble Fas ligand, granzyme B and cytochrome c during adjuvant chemotherapy of breast cancer. AB - BACKGROUND: Anticancer agents used in chemotherapy for tumors induce apoptosis in malignant cells. Soluble Fas ligand, granzyme B and cytochrome c are key elements in the process of apoptosis. The objective of this preliminary study was to evaluate the changes in the serum concentrations of these parameters in breast cancer patients undergoing adjuvant chemotherapy. MATERIALS AND METHODS: Sixty patients with histopathologically proven breast cancer were included in the present study. The blood samples were taken after surgery before chemotherapy and after 3weeks of administration of the first cycle of chemotherapy. Thirty healthy female controls were selected for comparison. Soluble FasL, granzyme B and cytochrome c were estimated from serum by ELISA. RESULTS: Significantly increased concentrations of soluble FasL, granzyme B and cytochrome c were found in stage II and stage III of breast cancer patients after chemotherapy compared with concentrations before chemotherapy (P<0.0001). A significant positive correlation was found between soluble FasL and cytochrome c as well as between granzyme B and cytochrome c in breast cancer patients after chemotherapy. CONCLUSION: Serum concentrations of apoptotic markers such as soluble FasL, granzyme B and cytochrome c were increased after administration of the first cycle of chemotherapeutic drugs. The measurement of these circulating apoptotic markers may help clinicians in evaluating treatment efficacy in breast cancer. PMID- 25139497 TI - What forgetting tells us about remembering: the influence of top-down control on hemispheric asymmetries in verbal memory. AB - It has been suggested that left hemisphere (LH) advantages in verbal processing is due to superior top-down control of verbal information. It is not clear how top-down mechanisms affect the encoding and retrieval of verbal information from hemispheric memory and whether they only influence activation or also encompass the inhibition of verbal information. The directed forgetting method, in conjunction with divided visual field presentation, was used to examine the influence of top-down control mechanisms on hemispheric asymmetries in verbal memory. Participants were cued to remember or forget words. Cues were presented either simultaneously with targets or after a short delay. A recognition memory test using divided visual field presentation was then given. Response times (RTs) revealed effects of cue timing in the LH. With simultaneous cues, RTs were faster to "Remember" words compared to "Forget" words. With delayed cues, RTs for "Remember" and "Forget" words were equivalent. In the right hemisphere (RH), "Remember" words were consistently faster than "Forget" words, regardless of cue timing. These data provide evidence that top-down mechanisms influenced LH verbal memory retrieval more than RH verbal memory retrieval. Finally, there was little evidence to suggest the hemispheres differ in inhibitory processing. PMID- 25139498 TI - Unexpected roles for ancient proteins: flavone 8-hydroxylase in sweet basil trichomes is a Rieske-type, PAO-family oxygenase. AB - Most elucidated hydroxylations in plant secondary metabolism are catalyzed by oxoglutarate- or cytochrome P450-dependent oxygenases. Numerous hydroxylations still evade clarification, suggesting that they might be performed by alternative enzyme types. Here, we report the identification of the flavone 8-hydroxylase (F8H) in sweet basil (Ocimum basilicum L.) trichomes as a Rieske-type oxygenase. Several features of the F8H activity in trichome protein extracts helped to differentiate it from a cytochrome P450-catalyzed reaction and identify candidate genes in the basil trichome EST database. The encoded ObF8H proteins share approximately 50% identity with Rieske-type protochlorophyllide a oxygenases (PTC52) from higher plants. Homology cloning and DNA blotting revealed the presence of several PTC52-like genes in the basil genome. The transcripts of the candidate gene designated ObF8H-1 are strongly enriched in trichomes compared to whole young leaves, indicating trichome-specific expression. The full-length ObF8H-1 protein possesses a predicted N-terminal transit peptide, which directs green fluorescent protein at least in part to chloroplasts. The F8H activity in crude trichome protein extracts correlates well with the abundance of ObF8H peptides. The purified recombinant ObF8H-1 displays high affinity for salvigenin and is inactive with other tested flavones except cirsimaritin, which is 8 hydroxylated with less than 0.2% relative activity. The efficiency of in vivo 8 hydroxylation by engineered yeast was improved by manipulation of protein subcellular targeting. blast searches showed that occurrence of several PTC52 like genes is rather common in sequenced plant genomes. The discovery of ObF8H suggests that Rieske-type oxygenases may represent overlooked candidate catalysts for oxygenations in specialized plant metabolism. PMID- 25139499 TI - "They Sweat for Science": The Harvard Fatigue Laboratory and Self-Experimentation in American Exercise Physiology. AB - In many scientific fields, the practice of self-experimentation waned over the course of the twentieth century. For exercise physiologists working today, however, the practice of self-experimentation is alive and well. This paper considers the role of the Harvard Fatigue Laboratory and its scientific director, D. Bruce Dill, in legitimizing the practice of self-experimentation in exercise physiology. Descriptions of self-experimentation are drawn from papers published by members of the Harvard Fatigue Lab. Attention is paid to the ethical and practical justifications for self-experimentation in both the lab and the field. Born out of the practical, immediate demands of fatigue protocols, self experimentation performed the long-term, epistemological function of uniting physiological data across time and space, enabling researchers to contribute to a general human biology program. PMID- 25139500 TI - Mesenchymal stromal cells as an adjuvant treatment for severe late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. AB - The management of severe late-onset hemorrhagic cystitis (LO-HC) after allogeneic hematopoietic stem cell transplantation (HSCT) is still challenging. Because mesenchymal stromal cells (MSCs) possess anti-inflammatory and tissue repair promoting properties, we retrospectively analyzed the efficacy and safety of MSC infusions in 7 of 33 patients with severe LO-HC after allogeneic HSCT. During treatment, each patient received at least one MSC infusion of Wharton's jelly derived from the umbilical cord of a third-party donor. In 6 patients, MSC treatment was initiated within 3 days of gross hematuria onset, while the 7th patient received an infusion 40 days later. The median dose was 1.0 (0.8-1.6) * 10(6)/kg. Five of 7 patients responded to treatment. Notably, gross hematuria promptly disappeared in 3 patients after 1 infusion, with a time to remission not seen in patients without MSC infusion. Two patients showed no response even after several infusions. No acute or late complications were recorded. Our findings indicate that MSC transfusion might be a feasible and safe supplemental therapy for patients with severe LO-HC after allogeneic HSCT. PMID- 25139501 TI - Interventional endoscopy for the treatment of pancreatic pseudocyst and walled off necrosis (with videos). AB - Pancreatic pseudocysts and walled-off necrosis are typical late complications of acute pancreatitis, and they require drainage in symptomatic cases presenting with infection. Transgastrointestinal endoscopic treatment with endoscopic ultrasound-guided drainage has become common and yields a good treatment outcome for pancreatic pseudocyst. Walled-off necrosis, however, contains necrotic tissue, and thus many cases additionally require an invasive treatment that includes endoscopic necrosectomy. Methods that involve a procedure-specific large diameter metal stent, additional endoscopic drainage techniques, and the hybrid approach method of adding percutaneous drainage have been described, and considerable advances in these methods have now made it possible to cure almost all cases of walled-off necrosis with endoscopic treatment alone. However, without being restricted to endoscopic treatments, a wide range of options including surgery should be considered as treatments for walled-off necrosis. PMID- 25139502 TI - A methodological review of the Short Form Health Survey 36 (SF-36) and its derivatives among breast cancer survivors. AB - PURPOSE: A systematic review of the validity, reliability and sensitivity of the Short Form (SF) health survey measures among breast cancer survivors. METHODS: We searched a number of databases for peer-reviewed papers. The methodological quality of the papers was assessed using the COnsenus-based Standards for the selection of health Measurement INstruments (COSMIN). RESULTS: The review identified seven papers that assessed the psychometric properties of the SF-36 (n = 5), partial SF-36 (n = 1) and SF-12 (n = 1) among breast cancer survivors. Internal consistency scores for the SF measures ranged from acceptable to good across a range of language and ethnic sub-groups. The SF-36 demonstrated good convergent validity with respective subscales of the Functional Assessment of Cancer Treatment-General scale and two lymphedema-specific measures. Divergent validity between the SF-36 and Lymph-ICF was modest. The SF-36 demonstrated good factor structure in the total breast cancer survivor study samples. However, the factor structure appeared to differ between specific language and ethnic sub groups. The SF-36 discriminated between survivors who reported or did not report symptoms on the Breast Cancer Prevention Trial Symptom Checklist and SF-36 physical sub-scales, but not mental sub-scales, discriminated between survivors with or without lymphedema. Methodological quality scores varied between and within papers. CONCLUSION: Short Form measures appear to provide a reliable and valid indication of general health status among breast cancer survivors though the limited data suggests that particular caution is required when interpreting scores provided by non-English language groups. Further research is required to test the sensitivity or responsiveness of the measure. PMID- 25139503 TI - Nestin downregulation in rat vascular smooth muscle cells represents an early marker of vascular disease in experimental type I diabetes. AB - BACKGROUND: Nestin was reported to directly contribute to cell proliferation and the intermediate filament protein was detected in vascular smooth muscle cells. In experimental type I diabetes, nestin downregulation in the heart was identified as an incipient pathophysiological event. The following study tested the hypothesis that dysregulation of nestin expression in vascular smooth muscle cells represented an early event of vascular disease in experimental type I diabetes. METHODS/RESULTS: In the carotid artery and aorta of adult male Sprague Dawley rats, a subpopulation of vascular smooth muscle cells co-expressed nestin and was actively involved in the cell cycle as reflected by the co-staining of nuclear phosphohistone-3. The infection of aortic vascular smooth muscle cells with a lentivirus containing a shRNAmir directed against nestin significantly reduced protein expression and concomitantly attenuated basal DNA synthesis. Two weeks following injection of adult male Sprague-Dawley rats with streptozotocin, the endothelial response of aortic rings to acetylcholine, vascular morphology and the total density of vascular smooth muscle cells in the vasculature of type I diabetic rats were similar to normal rats. By contrast, nestin protein levels and the density of nestin(+)/phosphohistone-3(+)-vascular smooth muscle cells were significantly reduced in type I diabetic rats. The in vivo observations were recapitulated in vitro as exposure of vascular smooth muscle cells to 30 mM D glucose inhibited DNA synthesis and concomitantly reduced nestin protein expression. CONCLUSIONS: Hyperglycaemia-mediated nestin downregulation and the concomitant reduction of cycling vascular smooth muscle cells represent early markers of vascular disease in experimental type I diabetes. PMID- 25139504 TI - Stages of recovery in early psychosis: Associations with symptoms, function, and narrative development. AB - OBJECTIVES: This study sought to explore the links between recovery stages, symptoms, function, and narrative development among individuals with a recent onset of psychosis. DESIGN: A qualitative longitudinal study was conducted including quantitative data at baseline. METHODS: Forty-seven participants were administered the Indiana Psychiatric Illness Interview three times over 9 months and content analysis was performed. Participants also completed the Social Functioning Scale, the Brief Psychiatric Rating Scale--Expanded, the California Verbal Learning Test, and the Trailing Making Test at baseline. Descriptive discriminant analysis was performed. RESULTS: Results suggested that participants were mostly in the first two stages of recovery (moratorium, awareness) and that being in the awareness, rather than moratorium, stage was associated, to a different extent, with richer narrative development, better levels of psychosocial function, less negative and positive symptoms, and more years of education. Furthermore, recovery appeared to be a stable process over the assessment period. CONCLUSIONS: Recovery is a complex concept including objective and subjective aspects. In the recovery path of persons recently diagnosed with psychosis, social engagement, narrative development, and occupational functioning seem to be particularly important aspects. This study is a first step, and future research is needed with larger and more diverse participant pools, and assessments conducted over longer periods of time. PRACTITIONER POINTS: As greater level of social engagement was the most robust predictor of membership in the awareness versus moratorium stage, treatment of early psychosis should include interventions targeting social relations and social skills. As greater narrative development was the second most robust predictor, enhancing it via psychotherapy could be a pertinent clinical goal. PMID- 25139505 TI - Ebola. PMID- 25139506 TI - Experimental countermeasures against Ebola virus: current progress and an ethical conundrum. PMID- 25139513 TI - Wide complex tachycardia: what is the mechanism? PMID- 25139514 TI - One-year vascular adaptations following pregnancies complicated by hypertension. PMID- 25139515 TI - Experts condemn "flawed" NICE process over its rejection of prostate cancer drug. PMID- 25139516 TI - Impact of advanced hearing aid technology on speech understanding for older listeners with mild to moderate, adult-onset, sensorineural hearing loss. AB - BACKGROUND: Hearing loss is one of the most common chronic health conditions of older people. Hearing aids are the customary treatment and they improve quality of life in older adults. Even so, relatively few older adults with uncomplicated, mild to moderate, adult-onset, sensorineural hearing loss use hearing aids. One reason for this is a belief that hearing aids do not provide sufficient value to justify their expense. Although modern hearing aids are available at several price points, there is minimal evidence about the relative benefits of premium level versus basic-level hearing aid technologies. OBJECTIVE: This research was designed to demonstrate the relative effectiveness of premium hearing aids compared with basic hearing aids in improving speech understanding and quality of life. METHODS: 25 participants, including both new and experienced hearing aid users, completed blinded month-long field trials with each of four pairs of hearing aids: two basic and two premium level. Outcomes were laboratory speech understanding tests, standardized questionnaires and open-ended diary items. RESULTS: Participants reacted very positively to all the hearing aids. Both everyday speech understanding and quality of life were substantially improved with hearing aids. RESULTS for both new and experienced users were consistent with a conclusion that there were no statistically significant or clinically important differences in improvement between the premium- and basic-level hearing aids. CONCLUSIONS: It should not be assumed that more costly hearing aids always produce better outcomes. With contemporary hearing aids from two major manufacturers, the subjects obtained as much improvement in speech understanding and quality of life from lower-cost basic-level instruments as from higher-cost premium-level instruments. Regardless of technology level, comprehensive best practice fitting protocols should be followed to optimize results for every patient. PMID- 25139517 TI - Preclinical evaluation and test-retest studies of [(18)F]PSS232, a novel radioligand for targeting metabotropic glutamate receptor 5 (mGlu5). AB - PURPOSE: A novel, (18)F-labelled metabotropic glutamate receptor subtype 5 (mGlu5) derivative of [(11)C]ABP688 ([(11)C]1), [(18)F]PSS232 ([(18)F] ]5), was evaluated in vitro and in vivo for its potential as a PET agent and was used in test-retest reliability studies METHODS: The radiosynthesis of [(18)F]5 was accomplished via a one-step reaction using a mesylate precursor. In vitro stability was determined in PBS and plasma, and with liver microsomal enzymes. Metabolite studies were performed using rat brain extracts, blood and urine. In vitro autoradiography was performed on horizontal slices of rat brain using 1 and 8, antagonists for mGlu5 and mGlu1, respectively. Small-animal PET, biodistribution, and test-retest studies were performed in Wistar rats. In vivo, dose-dependent displacement studies were performed using 6 and blocking studies with 7. RESULTS: [(18)F]5 was obtained in decay-corrected maximal radiochemical yield of 37 % with a specific activity of 80 - 400 GBq/MUmol. Treatment with rat and human microsomal enzymes in vitro for 60 min resulted in 20 % and 4 % of hydrophilic radiometabolites, respectively. No hydrophilic decomposition products or radiometabolites were found in PBS or plasma. In vitro autoradiography on rat brain slices showed a heterogeneous distribution consistent with the known distribution of mGlu5 with high binding to hippocampal and cortical regions, and negligible radioactivity in the cerebellum. Similar distribution of radioactivity was found in PET images. Under displacement conditions with 6, reduced [(18)F]5 binding was found in all brain regions except the cerebellum. 7 reduced binding in the striatum by 84 % on average. Test-retest studies were reproducible with a variability ranging from 6.8 % to 8.2 %. An extended single-dose toxicity study in Wistar rats showed no compound-related adverse effects. CONCLUSION: The new mGlu5 radiotracer, [(18)F]5, showed specific and selective in vitro and in vivo properties and is a promising radioligand for PET imaging of mGlu5 in humans. PMID- 25139518 TI - Incidental colonic focal FDG uptake on PET/CT: can the maximum standardized uptake value (SUVmax) guide us in the timing of colonoscopy? AB - PURPOSE: In patients undergoing (18)F-FDG PET/CT, incidental colonic focal lesions can be indicative of inflammatory, premalignant or malignant lesions. The maximum standardized uptake value (SUVmax) of these lesions, representing the FDG uptake intensity, might be helpful in differentiating malignant from benign lesions, and thereby be helpful in determining the urgency of colonoscopy. The aim of our study was to assess the incidence and underlying pathology of incidental PET-positive colonic lesions in a large cohort of patients, and to determine the usefulness of the SUVmax in differentiating benign from malignant pathology. METHODS: The electronic records of all patients who underwent FDG PET/CT from January 2010 to March 2013 in our hospital were retrospectively reviewed. The main indications for PET/CT were: characterization of an indeterminate mass on radiological imaging, suspicion or staging of malignancy, and suspicion of inflammation. In patients with incidental focal FDG uptake in the large bowel, data regarding subsequent colonoscopy were retrieved, if performed within 120 days. The final diagnosis was defined using colonoscopy findings, combined with additional histopathological assessment of the lesion, if applicable. RESULTS: Of 7,318 patients analysed, 359 (5 %) had 404 foci of unexpected colonic FDG uptake. In 242 of these 404 lesions (60 %), colonoscopy follow-up data were available. Final diagnoses were: adenocarcinoma in 25 (10 %), adenoma in 90 (37 %), and benign in 127 (53 %). The median [IQR] SUVmax was significantly higher in adenocarcinoma (16.6 [12 - 20.8]) than in benign lesions (8.2 [5.9 - 10.1]; p < 0.0001), non-advanced adenoma (8.3 [6.1 - 10.5]; p < 0.0001) and advanced adenoma (9.7 [7.2 - 12.6]; p < 0.001). The receiver operating characteristic curve of SUVmax for malignant versus nonmalignant lesions had an area under the curve of 0.868 (SD +/- 0.038), the optimal cut-off value being 11.4 (sensitivity 80 %, specificity 82 %, positive predictive value 34 %, negative predictive value 98 %). CONCLUSION: In these patients with incidental colonic focal activity undergoing PET/CT (the largest series published to date), malignancies had significantly higher SUVmax values than all other types of lesions. However, SUVmax could not distinguish between benign lesions and adenomas. In conclusion, all incidental findings in the colon should be further evaluated and lesions with SUVmax >=11.4 should be evaluated without delay. PMID- 25139519 TI - Diagnostic and therapeutic uses of nanomaterials in the brain. AB - Nanomedicine has recently emerged as an exciting tool able to improve the early diagnosis and treatment of a variety of intractable or age-related brain disorders. The most relevant properties of nanomaterials are that they can be engineered to cross the blood brain barrier, to target specific cells and molecules and to act as vehicles for drugs. Potentially beneficial properties of nanotherapeutics derived from its unique characteristics include improved efficacy, safety, sensitivity and personalization compared to conventional medicines. In this review, recent advances in available nanostructures and nanomaterials for brain applications will be described. Then, the latest applications of nanotechnology for the diagnosis and treatment of neurological disorders, in particular brain tumors and neurodegenerative diseases, will be reviewed. Recent investigations of the neurotoxicity of the nanomaterial both in vitro and in vivo will be summarized. Finally, the ongoing challenges that have to be meet if new nanomedical products are to be put on the market will be discussed and some future directions will be outlined. PMID- 25139520 TI - Ischemic colitis: A forgotten entity. Results of a retrospective study in 118 patients. AB - OBJECTIVE: The aim of our study was to document our 6-year experiences in identifying the clinical characteristics, laboratory findings, risk factors and the outcomes of patients with ischemic colitis (IC) in a community hospital setting. METHODS: The medical records of patients who were diagnosed with IC from 2007 to 2013 in two community hospitals were retrospectively reviewed. Their clinical characteristics, laboratory results, radiological, endoscopic and histological evidence, anatomic location of the lesion, comorbidities, concomitant use of drugs, and so on, were collected. RESULTS: A total of 118 patients with IC was identified, most were elderly individuals with a female predominance. The most common symptoms were abdominal pain, rectal bleeding and diarrhea. Hypertension, hyperlipidemia, coronary artery disease and diabetes mellitus were the most common comorbidities. Erythema, edema and erosions/ulcerations were the most common endoscopic findings. Left colon was the most affected location of lesion (84.8%), and there was one case of pancolitis. The descending colon was the most common affected segment, while rectum was the least affected segment. Severe IC occurred in 12.7% of the patients. Death within 30 days from the diagnosis of the disease occurred in 4.2%. CONCLUSIONS: IC is majorly occurred in elderly with a female predominance. Cardiovascular disease and its associated risk factors are the most common comorbidities. Left colon is the most affected location of the disease and the overall mortality rate was 4.2%. Physicians should make every effort to identify these patients, especially those with high risks. PMID- 25139521 TI - Memory traces of long-range coordinated oscillations in the sleeping human brain. AB - Cognition involves coordinated activity across distributed neuronal networks. Neuronal activity during learning triggers cortical plasticity that allows for reorganization of the neuronal network and integration of new information. Animal studies have shown post-learning reactivation of learning-elicited neuronal network activity during subsequent sleep, supporting consolidation of the reorganization. However, no previous studies, to our knowledge, have demonstrated reactivation of specific learning-elicited long-range functional connectivity during sleep in humans. We here show reactivation of learning-induced long-range synchronization of magnetoencephalography power fluctuations in human sleep. Visuomotor learning elicited a specific profile of long-range cortico-cortical synchronization of slow (0.1 Hz) fluctuations in beta band (12-30 Hz) power. The parieto-occipital part of this synchronization profile reappeared in delta band (1-3.5 Hz) power fluctuations during subsequent sleep, but not during the intervening wakefulness period. Individual differences in the reactivated synchronization predicted postsleep performance improvement. The presleep resting state synchronization profile was not reactivated during sleep. The findings demonstrate reactivation of long-range coordination of neuronal activity in humans, more specifically of reactivation of coupling of infra-slow fluctuations in oscillatory power. The spatiotemporal profile of delta power fluctuations during sleep may subserve memory consolidation by echoing coordinated activation elicited by prior learning. PMID- 25139522 TI - Renal denervation for treatment of hypertension and beyond. PMID- 25139523 TI - Blood pressure and blood flow find its way. PMID- 25139525 TI - Reconfigurable swarms of nematic colloids controlled by photoactivated surface patterns. AB - Different phoretic driving mechanisms have been proposed for the transport of solid or liquid microscopic inclusions in integrated chemical processes. It is now shown that a substrate that was chemically modified with photosensitive self assembled monolayers enables the direct control of the assembly and transport of large ensembles of micrometer-sized particles and drops that were dispersed in a thin layer of anisotropic fluid. This strategy separates particle driving, which was realized by AC electrophoresis, and steering, which was achieved by elastic modulation of the nematic host fluid. Inclusions respond individually or in collective modes following arbitrary reconfigurable paths that were imprinted by irradiation with UV or blue light. Relying solely on generic material properties, the proposed procedure is versatile enough for the development of applications that involve either inanimate or living materials. PMID- 25139524 TI - A spatial simulation model for dengue virus infection in urban areas. AB - BACKGROUND: The World Health Organization estimates that the global number of dengue infections range between 80-100 million per year, with some studies estimating approximately three times higher numbers. Furthermore, the geographic range of dengue virus transmission is extending with the disease now occurring more frequently in areas such as southern Europe. Ae. aegypti, one of the most prominent dengue vectors, is endemic to the far north-east of Australia and the city of Cairns frequently experiences dengue outbreaks which sometimes lead to large epidemics. METHOD: A spatially-explicit, individual-based mathematical model that accounts for the spread of dengue infection as a result of human movement and mosquito dispersion is presented. The model closely couples the four key sub-models necessary for representing the overall dynamics of the physical system, namely those describing mosquito population dynamics, human movement, virus transmission and vector control. Important features are the use of high quality outbreak data and mosquito trapping data for calibration and validation and a strategy to derive local mosquito abundance based on vegetation coverage and census data. RESULTS: The model has been calibrated using detailed 2003 dengue outbreak data from Cairns, together with census and mosquito trapping data, and is shown to realistically reproduce a further dengue outbreak. The simulation results replicating the 2008/2009 Cairns epidemic support several hypotheses (formulated previously) aimed at explaining the large-scale epidemic which occurred in 2008/2009; specifically, while warmer weather and increased human movement had only a small effect on the spread of the virus, a shorter virus strain-specific extrinsic incubation time can explain the observed explosive outbreak of 2008/2009. CONCLUSION: The proof-of-concept simulation model described in this study has potential as a tool for understanding factors contributing to dengue spread as well as planning and optimizing dengue control, including reducing the Ae. aegypti vector population and for estimating the effectiveness and cost-effectiveness of future vaccination programmes. This model could also be applied to other vector borne viral diseases such as chikungunya, also spread by Ae. aegypti and, by re-parameterisation of the vector sub-model, to dengue and chikungunya viruses spread by Aedes albopictus. PMID- 25139526 TI - Head-mounted display for a personal integrated image monitoring system: ureteral stent placement. AB - The personal head-mounted display (HMD) has emerged as a novel image monitoring system. We present here the application of a high-definition organic electroluminescent binocular HMD in ureteral stent placement. Our HMD system displayed multiple forms of information such as integrated, sharp, high-contrast images using a four-split screen or a picture-in-picture technique both seamlessly and synchronously. When both the operator and the assistant wore an HMD, they could continuously and simultaneously monitor the cystoscopic and fluoroscopic images in an ergonomically natural position. Furthermore, each participant was able to modulate the displayed images depending on the procedure. In all five cases, both the operator and the assistant successfully used this system with no unfavorable event. No participants experienced any HMD wear related adverse effects. We therefore believe this HMD system might be potentially beneficial during ureteral stent placement procedures. Furthermore, it is compact, easily introduced and affordable. PMID- 25139527 TI - 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cell death through modulating PI3K/Akt and JNK pathways. AB - We have recently shown that 7,8-dihydroxyflavone (7,8-DHF) protects PC12 cells against 6-OHDA-induced cytotoxicity through its antioxidant activity. In the present study, we investigated the molecular mechanisms underlying the neuronal protective activity of 7,8-DHF. Western blot analysis showed that 6-OHDA (100MUM, 24h) enhanced the phosphorylation of JNK and ERK1/2, but it markedly suppressed the expression of p-Akt, implying that 6-OHDA induces PC12 cell death through activating the pro-apoptotic MAPKs pathway but suppressing the survival PI3K/Akt pathway. More importantly, addition of 7,8-DHF fully prevented the activation of JNK and suppression of Akt induced by 6-OHDA. Interestingly, pretreatment with the PI3K-specific inhibitor LY294002 largely blocked 7,8-DHF function in protecting PC12 cells from 6-OHDA-induced cell death. In contrast, the MEK inhibitor PD98059 showed little effect on the protective activity of 7,8-DHF. These results suggest that 7,8-DHF might protect PC12 cells from 6-OHDA-induced cell death through activating PI3K/Akt pathway and inhibiting JNK pathway. PMID- 25139528 TI - Disruption reduces accuracy and P3b amplitudes in the attentional blink. AB - In everyday life, distracting stimuli often interfere with daily tasks, and disrupt successful task performance. The attentional blink paradigm (a deficit in reporting the second target (T2) in a rapid stream of visual stimuli) allows for an investigation of disruption by rapidly appearing stimuli. Specifically, the magnitude of the attentional blink deficit can be manipulated by positioning relevant stimuli at strategic locations within the visual stream. The current study therefore designed and tested a disruption paradigm that aimed to reduce T2 accuracy using a disruptor stimulus. Electroencephalography was used to reveal the neural correlates of the effect. To that end, targets were defined by task set colours. The item immediately preceding T2 appeared in a task-set colour (disrupted trials) or a different colour (non-disrupted trials). The results revealed that T2 accuracy was reduced on disrupted trials, and disruption appeared to be worse when T2 appeared inside the attentional blink window. The behavioural data were paralleled by the neural results. On trials where T2 appeared within the AB window and was correctly reported, T2-P3b amplitude (a neural correlate of working memory consolidation) was significantly depressed on disrupted trials compared with non-disrupted trials. Single trial plots of P3b amplitude confirmed a weaker neural trace for T2 on disrupted trials. These data indicate that the magnitude and neural signature of the attentional blink deficit is malleable, and can be influenced by non-target, task-relevant stimuli. PMID- 25139529 TI - rs11098403 polymorphism near NDST3 is associated with a reduced risk of schizophrenia in a Han Chinese population. AB - A recent genome-wide association study indicated that rs11098403, a single nucleotide polymorphism in the vicinity of NDST3, was strongly associated with the risk of schizophrenia in Caucasians. However, this relation has not been validated in other populations or ethnic groups. Herein, we conducted a case control study to investigate the association of rs11098403 polymorphism with the schizophrenia risk in a Han Chinese population comprising 440 schizophrenia patients and 450 control subjects. For the first time, we showed that the minor allele (G) of rs11098403 is closely associated with a reduced risk of schizophrenia (OR=0.614; 95% CI: 0.453-0.833; P=0.002; Power=0.832). Meanwhile, the G allele of rs11098403 seemed to reduce the schizophrenia risk via a dominant manner (GG+AG vs. AA, OR=0.526; 95% CI: 0.374-0.74; P<0.001). Furthermore, this association was further confirmed using an independent replication sample containing 267 schizophrenia patients and 400 control subjects with a Han Chinese descent (OR=0.652; 95% CI: 0.469-0.907; P=0.011; Power=0.772). Taken together, these findings demonstrate a significant association between rs11098403 and schizophrenia risk in Han Chinese, confirming the data that previously obtained from Caucasians. PMID- 25139530 TI - XLPE based Al2O3-clay binary and ternary hybrid nanocomposites: self-assembly of nanoscale hybrid fillers, polymer chain confinement and transport characteristics. AB - Transport properties of hybrid nanoparticle based cross-linked polyethylene (XLPE)-Al2O3-clay binary and ternary nanocomposites have been investigated with special significance to the hybrid effect and synergism of hybrid nanofillers. Compiling the temperature and filler effects demonstrates the self-assembly of hybrid nanofillers in confining the polymer chain dynamics. Studies on transport mechanisms, transport coefficients, and swelling parameters confirm the superior solvent resistant properties of hybrid filler reinforced nanocomposites. Experiments confirmed the extra stability of the ternary hybrid nanocomposites against the process of solvent penetration. Thermodynamic and kinetic investigations reveal that the nanofillers are competent to alter the thermodynamic feasibility and rate constant parameters. Theoretical predictions by the Peppas-Sahlin model suggest that the diffusion process is well thought-out to be a combination of diffusion into the swollen polymer and the polymer chain relaxation process. The morphology and the network density estimation confirm the presence of filler networks and the trapped polymer chains inside them, in ternary systems, which elucidate the microstructure assisted solvent resistant properties of the ternary hybrid nanocomposites. The amount of polymer chains immobilized by the filler surface was computed from dynamic mechanical analysis and a nice correlation was established between transport characteristics and the polymer chain confinement. PMID- 25139531 TI - Range expansion of Ixodes ricinus to higher altitude, and co-infestation of small rodents with Dermacentor marginatus in the Northern Apennines, Italy. AB - Immature ticks (Ixodes ricinus and Dermacentor marginatus) were collected from small rodents (Apodemus spp. and Myodes glareolus), in the Northern Apennines, Italy, at an altitude up to 1650 m above sea level (a.s.l.), from 2009 through 2012. While D. marginatus had been found at the same location in studies carried out in 1994, I. ricinus was very rare or absent. Prevalence (95% confidence interval) of infestation by I. ricinus larvae on Apodemus spp. was 54.4% (47.5, 61.2), and it was greater than prevalence of D. marginatus larvae on the same hosts (23.3%, 17.8, 29.5). The mean (standard deviation) numbers of I. ricinus and D. marginatus larvae per individual Apodemus spp. were similar: 2.3 (4.1) and 2.1 (9.8), respectively. The monthly infestation pattern of the two tick species on Apodemus spp. were different. I. ricinus larvae were more frequent in June and September, than in July-August. I. ricinus nymphs were generally rare, and were most frequently found in July. The prevalence of D. marginatus larvae peaked in July-August, whereas nymphs were mostly active in August-September. Increasing population densities of roe deer (Capreolus capreolus), and increasing temperatures, in the last decades, in the Apennine area might have contributed to the observed range expansion of I. ricinus. PMID- 25139532 TI - Preoperative chemoradiation therapy for esophageal cancer is a risk factor for the elevation of high mobility group box-1, leading to an increase in postoperative severe pulmonary complications. AB - We herein clarified the time course of changes in the serum high mobility group box chromosomal protein-1 (HMGB-1) concentrations in esophageal cancer patients after esophagectomy, and investigated whether the perioperative serum HMGB-1 levels correlate with the administration of neoadjuvant chemoradiation therapy (NACRT) and the postoperative clinical course, especially the occurrence of pulmonary complications, in such patients. Sixty patients who underwent right transthoracic esophagectomy for esophageal cancer were enrolled in this study. The relationship between the perioperative serum HMGB-1 levels and NACRT, and the postoperative severe pulmonary complications were evaluated. Patients with severe pulmonary complications (n = 44) tended to have undergone NACRT more often than those without severe pulmonary complications (n = 16). The preoperative and postoperative day 7 serum HMGB-1 concentrations were significantly higher in patients with severe pulmonary complications than those in patients without severe pulmonary complications. In the univariate and multivariate analyses, the use of NACRT and the preoperative elevations in the serum HMGB-1 levels (>4.2 ng/mL) were found to be significantly associated with pulmonary dysfunction. Furthermore, the response to NACRT was found to be significantly associated with the preoperative serum HMGB-1 levels. The use of NACRT contributes to preoperative serum HMGB-1 elevation, and these were risk factors for the occurrence of severe postoperative pulmonary complications in patients with esophageal cancer after thoracic esophagectomy. PMID- 25139533 TI - Increased oligodendrogenesis by humanin promotes axonal remyelination and neurological recovery in hypoxic/ischemic brains. AB - Oligodendrocytes are the predominant cell type in white matter and are highly vulnerable to ischemic injury. The role of oligodendrocyte dysfunction in ischemic brain injury is unknown. In this study, we used a 24-amino acid peptide S14G-Humanin (HNG) to examine oligodendrogenesis and neurological functional recovery in a hypoxic/ischemic (H/I) neonatal model. Intraperitoneal HNG pre treatment decreased infarct volume following H/I injury. Delayed HNG treatment 24 h after H/I injury did not reduce infarct volume but did decrease neurological deficits and brain atrophy. Delayed HNG treatment did not attenuate axonal demyelination at 48 h after H/I injury. However, at 14 d after H/I injury, delayed HNG treatment increased axonal remyelination, the thickness of corpus callosum at the midline, the number of Olig2(+) /BrdU(+) cells, and levels of brain-derived neurotrophic factor (BDNF). Our results suggest that targeting oligodendrogenesis via delayed HNG treatment may represent a promising approach for the treatment of stroke. PMID- 25139534 TI - Molecular features and survival outcomes of the intrinsic subtypes within HER2 positive breast cancer. AB - BACKGROUND: The clinical impact of the biological heterogeneity within HER2 positive (HER2+) breast cancer is not fully understood. Here, we evaluated the molecular features and survival outcomes of the intrinsic subtypes within HER2+ breast cancer. METHODS: We interrogated The Cancer Genome Atlas (n = 495) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets (n = 1730) of primary breast cancers for molecular data derived from DNA, RNA and protein, and determined intrinsic subtype. Clinical HER2 status was defined according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines or DNA copy-number aberration by single nucleotide polymorphism arrays. Cox models tested the prognostic significance of each variable in patients not treated with trastuzumab (n = 1711). RESULTS: Compared with clinically HER2 (cHER2)-negative breast cancer, cHER2+ breast cancer had a higher frequency of the HER2-enriched (HER2E) subtype (47.0% vs 7.1%) and a lower frequency of Luminal A (10.7% vs 39.0%) and Basal-like (14.1% vs 23.4%) subtypes. The likelihood of cHER2-positivity in HER2E, Luminal B, Basal-like and Luminal A subtypes was 64.6%, 20.0%, 14.4% and 7.3%, respectively. Within each subtype, only 0.3% to 3.9% of genes were found differentially expressed between cHER2+ and cHER2-negative tumors. Within cHER2+ tumors, HER2 gene and protein expression was statistically significantly higher in the HER2E and Basal-like subtypes than either luminal subtype. Neither cHER2 status nor the new 10-subtype copy number based classification system (IntClust) added independent prognostic value to intrinsic subtype. CONCLUSIONS: When the intrinsic subtypes are taken into account, cHER2-positivity does not translate into large changes in the expression of downstream signaling pathways, nor does it affect patient survival in the absence of HER2 targeting. PMID- 25139535 TI - HER2-positive breast cancer, intrinsic subtypes, and tailoring therapy. PMID- 25139536 TI - Commentary: Socioeconomic status and hypertension in low- and middle-income countries: can we learn anything from existing studies? PMID- 25139537 TI - Rejoinder: Socioeconomic gradients and hypertension in low- and middle-income countries: a straw man and no solutions. PMID- 25139538 TI - Comparison of Chinese and international psychiatrists' views on classification of mental disorders. AB - INTRODUCTION: This study aimed to explore the views and attitudes of Chinese psychiatrists on mental disorders classification, and to compare their similarities and differences with those of the international mental health professionals. METHODS: Two hundred and ninety members of the Chinese Society of Psychiatry were invited to participate in the study and 211 completed the survey. RESULTS: Ninety-one percent of Chinese participants regularly used a formal classification system, with more users of the International Classification of Diseases 10th Revision (ICD-10; 48.8%) or Chinese Classification of Mental Disorders 3rd Edition (39.3%) than the 4th Edition of Diagnostic and Statistical Manual (11.4%). Like their global counterparts, Chinese respondents regarded communication among clinicians as the most important purpose of a classification and preferred a simpler system with fewer categories. Chinese psychiatrists were more likely than international participants to prefer a system with strict diagnostic criteria for all disorders and to endorse problems with a cultural applicability of the classification. However, only a minority (31.3%) indicated that they saw a need for a national classification. DISCUSSION: Overall, Chinese psychiatrists have similar opinions and attitudes on most issues of the classification to the international clinicians. Areas of divergent views may provide meaningful information for ICD revision in China. PMID- 25139539 TI - Investigating the role of neuropathic pain relief in decreasing gait variability in diabetes mellitus patients with neuropathic pain: a randomized, double-blind crossover trial. AB - BACKGROUND: Subjects with diabetes mellitus (DM) develop gait dysfunction contributing to falls, reluctance to perform activities and injuries. Neuropathic pain (NeP) related to diabetic peripheral neuropathy (DPN) is associated with increased gait variability that may contribute to gait dysfunction. We used a portable device (GaitMeterTM) and related gait and balance measures to measure gait parameters in painful DPN (PDPN) subjects prior to and during analgesia. Our hypothesis was that PDPN subjects would have decreased gait step variability when receiving pharmacological relief of NeP. METHODS: DPN subjects with at least moderate NeP were assessed in a randomized, double-blind crossover study of pregabalin versus placebo. The outcome measure was variability in step length and step velocity. Testing for Timed Get-Up-and-Go Test, Tinetti Mobility Scales, Sway Testing, a Physiological Profile Approach, and fall-related surveys were also performed. DPN severity was quantified using the Utah Early Neuropathy Score. RESULTS: PDPN subjects developed increased, rather than decreased, step length and step velocity variability during pregabalin treatment. There were no significant differences between cohorts for other physiological gait and balance testing. Non-significant NeP relief occurred in the pregabalin phase of study as compared with placebo. There was a negative relationship for step length with pain severity. CONCLUSION: Analgesia did not decrease gait variability in PDPN patients, and in fact, increased gait variability was seen during pregabalin treatment. Other important relationships of gait dysfunction with PDPN should be sought. PMID- 25139540 TI - Routine plasma biochemistry analytes in clinically healthy cats: within-day variations and effects of a standard meal. AB - Limited information is available on pre-analytical variations in plasma analytes in cats. The objectives of this study were to assess the effects of the time of sampling and a standard meal on plasma analytes in healthy cats. Eight healthy, adult, fasted cats underwent blood sampling every 2 h from 8 am to 8 pm twice at a 12 day interval. On the days of sampling, four cats were kept fasted and the others were fed just after the first sample, in a crossover design. Plasma glucose, urea, creatinine, sodium, potassium, chloride, CO2, calcium, phosphate, proteins, albumin, cholesterol and triglycerides, alanine aminotransferase and alkaline phosphatase were assayed on each sample. Effects of time of sampling and meal on plasma biochemistry results were tested using a general linear model. Diurnal variations in tested plasma analytes in fasted cats were negligible except for urea and creatinine, which gave noticeably higher plasma concentrations in the afternoon than in the morning. Observed postprandial variations were of some importance for phosphate and creatinine and of indisputable clinical relevance for CO2 and urea. PMID- 25139542 TI - Cosmetic surgeon is struck off for putting commercial interests ahead of his patients. PMID- 25139543 TI - Selective transamidation of 3-oxo-N-acyl homoserine lactones by hydrazine derivatives. AB - A method for the selective transamidation of the 3-oxo sub-family of N-acyl homoserine lactones (3-oxo-AHLs) under physiologically relevant conditions has been developed. The reaction has the potential to serve as a strategy for selective knockdown of key autoinducers in a multicellular environment. PMID- 25139544 TI - Chondroitin sulfate glycosaminoglycans for CNS homeostasis-implications for material design. AB - Chondroitin sulfate proteoglycans (CSPGs) are complex biomolecules that are known to facilitate patterning of axonal direction and cell migration during the early growth and development phase of the mammalian central nervous system (CNS). In adults, they continue to control neuronal plasticity as major constituents of the "peri-neuronal nets" (PNNs) that surround adult CNS neurons. CSPGs are also barrier-forming molecules that are selectively upregulated by invading reactive astroglia after injury to the CNS, and are responsible for the active repulsion of regenerating neurons post-injury. Recent evidence however suggests that the diverse sulfated glycosaminoglycan (GAG) side chains attached to CSPGs are key components that play paradoxical roles in influencing nerve regeneration post injury to the CNS. Sulfated GAG repeats attached to the CSPG core protein help mediate cell migration, neuritogenesis, axonal pathfinding, and axonal repulsion by directly trapping and presenting a whole host of growth factors to cells locally, or by binding to specific membrane bound proteins on the cell surface to influence cellular function. In this review, we will present the current gamut of interventional strategies used to bridge CNS deficits, and discuss the potential advantages of using sulfated GAG based biomaterials to facilitate the repair and regeneration of the injured CNS. PMID- 25139545 TI - Mutations in the NS5A gene of hepatitis C virus subtype 1b and response to peg IFNalpha-2a/RBV combination therapy in Azerbaijani patients. AB - Hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease throughout the world. The presence of mutations in different regions of the HCV subtype 1b (HCV-1b) nonstructural 5A (NS5A) gene may be associated with response to interferon therapy. This study evaluated whether amino acid substitutions in the NS5A protein of HCV-1b correlated with response to pegylated interferon alfa-2a (peg-IFNalpha-2a) and ribavirin (RBV) combination therapy in Azerbaijani patients. From March 2010 to April 2014, a total of 34 chronically HCV-1b-infected Azerbaijani patients were enrolled in this prospective study. After extraction of RNA from plasma specimens, the entire sequences of the NS5A gene of HCV was amplified by reverse transcription nested polymerase chain reaction (RT-nested PCR), and the PCR products were sequenced subsequently. The data that were obtained revealed that there was no correlation between the response to HCV combination therapy and the number of mutations in the NS5A PKRBD, NS5A-ISDR, and NS5A-V3 regions of HCV. It also was found that changes from isoleucine to valine (I2252 V), aspartic acid to glutamic acid (D2257), arginine to lysine (R2269 K), and arginine to glycine in NS5A-PKRBD and from glycine to glutamic acid (G2379E) in the NS5A-V3 region were not associated with HCV treatment outcome. This study showed that genetic variability in the NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 regions is not a predictive factor of SVR, NR or relapse in HCV genotype1b treated with peg-IFNalpha-2a/RBV combination therapy. PMID- 25139546 TI - Replication of Chinese sacbrood virus in primary cell cultures of Asian honeybee (Apis cerana). AB - A primary cell culture system was established for the first time from embryonic tissues of Asian honeybee, Apis cerana, and used to trace the early infection process of Chinese sacbrood virus (CSBV), an iflavirus in the family Iflaviridae. A monolayer of epithelium-like cells of A. cerana, approximately 8-10 MUm in diameter, was grown in Kimura's insect medium at 28 degrees C within 3-4 days of setting up the cultures. Such cultured cells were inoculated with CSBV purified from infected larvae or pupae for 2 h. In electron and confocal micrographs, viral particles accumulated as filamentous or vesicular inclusions in the cytoplasm of infected cultured cells at 36 h post-inoculation (hpi). Real-time quantitative RT-PCR assay showed that the expression levels of four cistrons of CSBV in the cultured cells increased rapidly between 12 and 48 hpi. This newly established primary cell culture derived from A. cerana will be useful for further studies of infection caused by CSBV. PMID- 25139547 TI - Experimental inoculation of equine coronavirus into Japanese draft horses. AB - Recently, outbreaks associated with equine coronavirus (ECoV) have occurred in Japan and the United States. While ECoV is likely to be pathogenic to horses, it has not been shown that experimental inoculation of horses with ECoV produces clinical signs of disease. In this study, we inoculated three Japanese draft horses with an ECoV-positive diarrheic fecal sample to confirm infection after inoculation and to investigate the clinical course and virus shedding patterns of ECoV. Virus neutralization tests showed that all three horses became infected with ECoV. Two of the three horses developed clinical signs similar to those observed during ECoV outbreaks, including fever, anorexia, and gastrointestinal dysfunction. All horses excreted a large amount of virus into their feces for more than 9 days after inoculation regardless of the presence or absence of clinical signs, which suggests that feces are an important source of ECoV infection. ECoV was also detected in nasal swabs from all horses, suggesting that respiratory transmission of ECoV may occur. Both symptomatic horses developed viremia, while the asymptomatic horse did not. White blood cell counts and serum amyloid A concentrations changed relative to the clinical condition of the inoculated horses; these may be useful markers for monitoring the clinical status of horses infected with ECoV. This is the first report of induction of clinical signs of ECoV infection in horses by experimental inoculation. These clinical and virological findings should aid further investigation of the pathogenesis of ECoV. PMID- 25139548 TI - Is postoperative computed tomography evaluation a prognostic indicator in patients with optimally debulked advanced ovarian cancer? AB - OBJECTIVE: To compare the surgeon's intraoperative assessment of residual tumor (RT) disease with that identified on postoperative computed tomography (CT) in patients undergoing optimal primary surgical cytoreduction (RT <1 cm) and to identify the prognostic significance of postoperative CT scan of RT. METHODS: Patients with FIGO stage III-IV ovarian cancer treated at the Gynecologic Oncology Unit of the National Cancer Institute between November 2011 and March 2013, who underwent optimal primary cytoreduction and were entered in prospective controlled clinical trials requiring a baseline postoperative CT evaluation within 30 days, were enrolled. All CT scans were reviewed by a dedicated radiologist to evaluate RT. Median follow-up was 16 months. RESULTS: 64 out of 160 patients met the eligibility criteria. RT = 0, 0.1 < RT < 0.5 cm, and 0.6 < RT < 1 cm was reported in 53 (82.8%), 9 (14.1%) and 2 (3.1%) cases, respectively. Postoperative CT disagreed with RT in 13 out of 64 (20.3%) cases. Progression free survival (PFS) of patients with a positive and negative postoperative CT scan of RT was 5 months (95% CI 1-15 months) and 28 months (95% CI 2-46 months), respectively (p < 0.0001). Evidence of the disease using postoperative CT was an independent prognostic factor in multivariate analysis (HR = 8.87, 95% CI = 3.23 24.31, p < 0.0001). CONCLUSIONS: Evidence of the disease using postoperative CT was associated with a significant decrease in PFS in patients who underwent optimal primary cytoreduction. RT status as evaluated with early postoperative CT may have an important role in prognostic assessment. PMID- 25139549 TI - Reply to the letter to the editor 'second-line chemotherapy in advanced biliary cancer: the present now will later be past' by Vivaldi et al. PMID- 25139550 TI - A phase II randomized study evaluating the addition of iniparib to gemcitabine plus cisplatin as first-line therapy for metastatic non-small-cell lung cancer. AB - BACKGROUND: Iniparib is a novel anticancer agent initially considered a poly (ADP ribose) polymerase (PARP) inhibitor, but subsequently shown to act via non selective protein modification through cysteine adducts. This randomized phase II study investigated the addition of iniparib to gemcitabine-cisplatin in metastatic non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Patients with histologically confirmed stage IV NSCLC were randomized 2 : 1 to receive gemcitabine (1250 mg/m(2), days 1/8) and cisplatin (75 mg/m(2), day 1) with [gemcitabine/cisplatin/iniparib (GCI)] or without [gemcitabine/cisplatin (GC)] iniparib (5.6 mg/kg, days 1/4/8/11) every 3 weeks for six cycles. The primary end point was the overall response rate (ORR). Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety. The study was not designed for formal efficacy comparison, the control arm being to benchmark results against the literature. RESULTS: One hundred and nineteen patients were randomized (39 GC and 80 GCI). More GCI patients were male (80% GCI and 67% GC) and had PS 0 (61% GCI and 49% GC). The ORR was 25.6% [95% confidence interval (CI) 13.0%-42.1%] with GC versus 20.0% (95% CI 11.9%-30.4%) with GCI, which did not allow rejection of the null hypothesis (ORR with GCI <=20%; P = 0.545). Median PFS was 4.3 (95% CI 2.8-5.6) months with GC and 5.7 (95% CI 4.6 6.6) months with GCI (hazard ratio 0.89, 95% CI 0.56-1.40). Median OS was 8.5 (95% CI 5.5 to not reached) months with GC, and 12.0 (95% CI 8.9-17.1) months with GCI (hazard ratio 0.78, 95% CI 0.48-1.27). More GCI patients received second line treatment (51% GC and 68% GCI). Toxicity was similar in the two arms. Grade 3-4 toxicities included asthenia (28% GC and 8% GCI), nausea (3% GC and 14% GCI), and decreased appetite (10% in each). CONCLUSIONS: Addition of iniparib to GC did not improve ORR over GC alone. The GCI safety profile was comparable to GC alone. Imbalances in PS and gender distribution may have impacted study results regarding PFS and OS. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT01086254. PMID- 25139551 TI - Antihypertensive medication exposure and cardiovascular outcomes in hemodialysis patients. AB - BACKGROUND/AIMS: Our understanding of the effectiveness of cardioprotective medications in maintenance dialysis patients is based upon drug exposures assessed at a single point in time. We employed a novel, time-dependent approach to modeling medication use over time to examine outcomes in a large national cohort. METHODS: We linked Medicaid prescription claims with United States Renal Data System registry data and Medicare claims for 52,922 hypertensive maintenance dialysis patients. All-cause mortality and a combined cardiovascular disease (CVD)-endpoint were modeled as functions of exposure to cardioprotective antihypertensive medications (renin angiotensin system antagonists, beta adrenergic blockers, and calcium channel blockers) measured with three time dependent covariates (weekly exposure status, proportion of prior weeks with exposure, and number of switches in exposure status) and with propensity adjustment. RESULTS: Current cardioprotective medication exposure status as compared to not exposed was associated with lower adjusted hazard ratios (AHRs) for mortality, though the magnitude depended upon the proportion of prior weeks with medication (duration) and the number of switches between active and non active use (switches) (AHR range 0.54-0.90). Combined CVD-endpoints depended upon the proportion of weeks on medication: AHR = 1.18 for 10% and AHR = 0.90 for 90% of weeks. Combined CVD-endpoint was also lower for patients with fewer switches. CONCLUSIONS: Effectiveness depends not only on having a drug available but is tempered by duration and stability of use, likely reflecting variation in clinical stability and patient behavior. PMID- 25139552 TI - A Retrospective Review of the Clinical Experience of Linezolid with or Without Rifampicin in Prosthetic Joint Infections Treated with Debridement and Implant Retention. AB - INTRODUCTION: Debridement and prosthesis retention, combined with a prolonged antibiotic regimen including rifampicin, is an accepted therapeutic approach when the duration of symptoms is less than 4 weeks and there are no radiological signs of loosening. The outcome of patients managed with this strategy has been previously assessed in several articles with success rates of 60-90%. This study aims to review the clinical experience with linezolid in 3 different hospitals from Spain and France in patients with prosthetic joint infection (PJI) managed with debridement, retention of the implant and treated with linezolid with or without rifampicin. METHODS: Patients with an acute PJI who underwent open debridement with implant retention treated with linezolid for more than 7 days in 3 hospitals from Barcelona, Tours and Lille between 2005 and 2011 were retrospectively reviewed. Relevant information about demographics, co-morbidity, type of implant, surgical treatment, microorganism isolated, antimicrobial therapy, adverse events (AEs) and outcomes were recorded from patients. RESULTS: A total of 39 patients were retrospectively reviewed. The mean age (SD) was 70.5 (8.8) years and 9 patients had diabetes mellitus (23%). There were 25 (64%) knee prostheses, 13 (33%) hips and 1 shoulder (3%). The median interquartile range (IQR) days from arthroplasty to infection diagnosis was 17 (19-48) and 33 (85%) cases were diagnosed within the first 60 days. The median (IQR) duration of antibiotic treatment was 70.5 (34-96) days and the median (IQR) number of days on linezolid treatment was 44.5 (30-81). AEs were observed in 15 patients (38%), with gastrointestinal complaints in 8 cases and anemia in 5 being the most frequent. After a median (IQR) follow-up of 2.5 (1.8-3.6) years, there were 11 failures (28%) (8 relapses and 3 new infections). The failure rate was higher in the rifampicin group (36% vs. 18%) mainly due to a higher relapse rate (27% vs. 12%) although differences were not statistically significant. CONCLUSION: Management of acute PJIs with debridement and retention of the implant linezolid, with or without rifampicin, is associated with a high remission rate and it is an alternative treatment for infections due to fluoroquinolone and/or rifampicin resistant staphylococci. PMID- 25139553 TI - Searching for the molecular benchmark of physiological intestinal anastomotic healing in rats: an experimental study. AB - PURPOSE: This investigation focuses on the physiological characteristics of gene transcription of intestinal tissue following anastomosis formation. METHODS: In eight rats, end-to-end ileo-ileal anastomoses were performed (n = 2/group). The healthy intestinal tissue resected for this operation was used as a control. On days 0, 2, 4 and 8, 10-mm perianastomotic segments were resected. Control and perianastomotic segments were examined with an Affymetrix microarray chip to assess changes in gene regulation. Microarray findings were validated using real time PCR for selected genes. In addition to screening global gene expression, we identified genes intensely regulated during healing and also subjected our data sets to an overrepresentation analysis using the Gene Ontology (GO) and Kyoto Encyclopedia for Genes and Genomes (KEGG). RESULTS: Compared to the control group, we observed that the number of differentially regulated genes peaked on day 2 with a total of 2,238 genes, decreasing by day 4 to 1,687 genes and to 1,407 genes by day 8. PCR validation for matrix metalloproteinases-3 and -13 showed not only identical transcription patterns but also analogous regulation intensity. When setting the cutoff of upregulation at 10-fold to identify genes likely to be relevant, the total gene count was significantly lower with 55, 45 and 37 genes on days 2, 4 and 8, respectively. A total of 947 GO subcategories were significantly overrepresented during anastomotic healing. Furthermore, 23 overrepresented KEGG pathways were identified. CONCLUSION: This study is the first of its kind that focuses explicitly on gene transcription during intestinal anastomotic healing under standardized conditions. Our work sets a foundation for further studies toward a more profound understanding of the physiology of anastomotic healing. PMID- 25139554 TI - Surgical electronic logbook: A step forward. AB - INTRODUCTION: The surgical electronic logbook (surgical e-logbook) aims to: simplify registration of the training activities of surgical residents, and to obtain reliable and detailed reports about these activities for resident evaluation. METHODS: The surgical e-logbook is a unique and shared database. Residents prospectively record their activities in 3 areas: surgical, scientific and teaching. We can access activity reports that are constantly updated. RESULTS: Study period using the surgical e-logbook: Between June 2011 and May 2013. Number of surgeries reported: 4,255. Number of surgical procedures reported: 11,907. Number of surgeries per resident per year reported: 250. Number of surgical procedures per resident per year reported: 700. Surgical activity as a primary surgeon during the first year of residency is primarily in emergency surgery (68,01%) and by laparotomy (97,73%), while during the fifth year of residency 51,27% is performed in elective surgery and laparoscopy is used in 23,10% of cases. During this period, residents participated in a total of 11 scientific publications, 75 conference presentations and 69 continuing education activities. CONCLUSIONS: The surgical e-logbook is a useful tool that simplifies the recording and analysis of data about surgical and scientific activities of the residents. It is a step forward in the evaluation of the training of surgical residents, however, is only an intermediate step towards the development of a larger Spanish registry. PMID- 25139555 TI - Thoracic aortic cannulation with antegrade perfusion for the procurement of abdominal organs. AB - The definitive acceptance of an organ as valid for transplant depends on the surgical team performing the multiorgan recovery; and unexpected difficulties can occur. The demographic characteristics of donors has changed, and some accepted donors can present difficulties in surgical technique and risky decisions on the validity of the retrieved organ or organs. An alternative method to the cannulation of the abdominal aorta is proposed when there is evidence of disease in the infrarenal aorta during the multiorgan procurement. The retrocardiac descending thoracic aorta is cannulated using an antegrade perfusion; this technique allows an increase in organ recovery. PMID- 25139556 TI - Evaluation of the influence of metabolic processes and body composition on cognitive functions: Nutrition and Dementia Project (NutrDem Project). AB - The global increase in the prevalence of dementia and its associated comorbidities and consequences has stimulated intensive research focused on better understanding of the basic mechanisms and the possibilities to prevent and/or treat cognitive decline or dementia. The etiology of cognitive decline and dementia is very complex and is based upon the interplay of genetic and environmental factors. A growing body of epidemiological evidence has suggested that metabolic syndrome and its components may be important in the development of cognitive decline. Furthermore, an abnormal body mass index in middle age has been considered as a predictor for the development of dementia. The Nutrition and Dementia Project (NutrDem Project) was started at the Department of Old Age Psychiatry and Psychotic Disorders with close cooperation with Department of Medical Psychology. The aim of this study is to determine the effect of dietary patterns, nutritional status, body composition (with evaluation of visceral fat) and basic regulatory mechanisms of metabolism in elderly patients on cognitive functions and the risk of cognitive impairment (mild cognitive impairment and/or dementia). PMID- 25139557 TI - Bioelectrical impedance vector analysis (BIVA) for the assessment of two compartment body composition. AB - This review is directed to define the efficacy of bioelectrical impedance vector analysis (BIVA) for assessing two-compartment body composition. A systematic literature review using MEDLINE database up to 12 February 2014 was performed. The list of papers citing the first description of BIVA, obtained from SCOPUS, and the reference lists of included studies were also searched. Selection criteria included studies comparing the results of BIVA with those of other techniques, and studies analyzing bioelectrical vectors of obese, athletic, cachectic and lean individuals. Thirty articles met the inclusion criteria. The ability of classic BIVA for assessing two-compartment body composition has been mainly evaluated by means of indirect techniques, such as anthropometry and bioelectrical impedance analysis (BIA). Classic BIVA showed a high agreement with body mass index, that can be interpreted in relation to the greater body mass of obese and athletic individuals, whereas the comparison with BIA showed less consistent results, especially in diseased individuals. When a reference method was used, classic BIVA failed to accurately recognize FM% variations, whereas specific BIVA furnished good results. Specific BIVA is a promising alternative to classic BIVA for assessing two-compartment body composition, with potential application in nutritional, sport and geriatric medicine. PMID- 25139558 TI - Measuring diet in primary school children aged 8-11 years: validation of the Child and Diet Evaluation Tool (CADET) with an emphasis on fruit and vegetable intake. AB - BACKGROUND/OBJECTIVES: The Child And Diet Evaluation Tool (CADET) is a 24-h food diary that measures the nutrition intake of children aged 3-7 years, with a focus on fruit and vegetable consumption. Until now CADET has not been used to measure nutrient intake of children aged 8-11 years. To ensure that newly assigned portion sizes for this older age group were valid, participants were asked to complete the CADET diary (the school and home food diary) concurrently with a 1 day weighed record. SUBJECTS/METHODS: A total of 67 children with a mean age of 9.3 years (s.d.: +/- 1.4, 51% girls) participated in the study. Total fruit and vegetable intake in grams and other nutrients were extracted to compare the mean intakes from the CADET diary and Weighed record using t-tests and Pearson's r correlations. Bland-Altman analysis was also conducted to assess the agreement between the two methods. RESULTS: Correlations comparing the CADET diary to the weighed record were high for fruit, vegetables and combined fruit and vegetables (r=0.7). The results from the Bland-Altman plots revealed a mean difference of 54 g (95% confidence interval: -88, 152) for combined fruit and vegetables intake. CADET is the only tool recommended by the National Obesity Observatory that has been validated in a U.K. population and provides nutrient level data on children's diets. CONCLUSIONS: The results from this study conclude that CADET can provide high-quality nutrient data suitable for evaluating intervention studies now for children aged 3-11 years with a focus on fruit and vegetable intake. PMID- 25139559 TI - Assessment and definition of lean body mass deficiency in the elderly. AB - Although the effect of age on body composition has been intensively discussed during the past 20 years, we do not have a uniform definition of sarcopenia. A suitable definition of low, lean body mass should be based on magnetic resonance imaging (MRI) estimates of muscle mass. Using recent MRI data of a population of 446 healthy free-living Caucasian volunteers (247 females, 199 males) age 18-78 years, a low skeletal muscle mass and sarcopenia were defined as a skeletal muscle mass >1 and >2 s.d. below the mean value obeserved in younger adults at age 18-39 years. The cutoffs for low muscle mass according to the skeletal muscle index (skeletal muscle mass/(height)(2)) or the appendicular skeletal muscle mass index (skeletal muscle mass of the limbs/(height)(2)) were 6.75 or 4.36 kg/m(2) for females and 8.67 or 5.54 kg/m(2) for males, respectively. On the basis of these cutoffs, prevalences of sarcopenia in the group of adults at >60 years are calculated to be 29% in females and 19.0% in males. Faced with different sarcopenic phenotypes (that is, sarcopenia related to frailty and osteopenia; sarcopenic obesity related to metabolic risks; cachexia related to wasting diseases), future definitions of sarcopenia should be extended to the relations between (i) muscle mass and adipose tissue and (ii) muscle mass and bone mass. Suitable cutoffs should be based on the associations between estimates of body compositions and metabolic risks (for axample, insulin resistance), inflammation and muscle function (that is, muscle strength). PMID- 25139560 TI - Long-term exposure of human gingival fibroblasts to cigarette smoke condensate reduces cell growth by modulating Bax, caspase-3 and p53 expression. AB - BACKGROUND AND OBJECTIVE: Smoking cigarettes increases the risk of oral tissue damage leading to periodontal disease. Gingival fibroblasts, the predominant cell type inhabiting gingival connective tissue, play a critical role in remodeling and maintaining gingival structure. The objective of this study was to investigate the effect of long-term exposure to cigarette smoke on human gingival fibroblast survival/apoptosis and the molecular pathways involved in these cell responses. MATERIAL AND METHODS: Human gingival fibroblasts were extracted from healthy non-smokers and cultured in the presence of cigarette smoke condensate (CSC). At the end of each time point, cell growth was evaluated by means of MTT assay. Apoptotic and necrotic gene's expression was investigated by polymerase chain reaction array and by annexin V/propidium iodide staining and cell cycle assays. Western blot was used to investigate Bax and p53 proteins. These tests were supported by caspase 3 activity analyses. RESULTS: High levels of CSC decreased cell growth and deregulated cell cycle progression by increasing the G(0)/G(1) and reducing the S and G(2)/M phases of the gingival fibroblasts. Polymerase chain reaction arrays revealed the activation of several apoptotic genes by CSC, including TNF receptors, caspases, Bax and p53. This was supported by increases in the Bax and p53 protein levels as well as by an elevated activity of caspase-3 in the CSC-exposed cells. Immunofluorescence staining demonstrated that both Bax and caspase-3 displayed a cytosolic and mitochondrial distribution in the CSC-exposed gingival fibroblasts, compared to controls. The damaging effect of CSC on gingival fibroblast growth was also supported by the decrease in interleukin 6 and 8 secretion by the gingival fibroblasts. CONCLUSION: These results suggest that CSC may contribute to deregulating fibroblast functions. This can compromise fibroblast-epithelial cell interactions, which ultimately increases the risk of gingival tissue damage and the onset of periodontitis. PMID- 25139561 TI - Tissue-specific actions of FXR in metabolism and cancer. AB - The nuclear Farnesoid X Receptor (FXR) is a transcription factor critically involved in metabolic homeostasis in the gut-liver axis. FXR activity is mediated by hormonal and dietary signals and driven by bile acids (BAs), which are the natural FXR ligands. Given the great physiological importance in BA homeostasis, as well as in the regulation of glucose and lipid metabolism, FXR plays a pivotal role in the pathogenesis of a wide range of disease of the liver, biliary tract and intestine, including hepatic and colorectal cancer. In the last years several studies have shown the relative FXR tissue-specific importance, highlighting synergism and additive effects in the liver and intestine. Gain- and loss-of-FXR function mouse models have been generated in order to identify the biological processes and the molecular FXR targets. Taking advantage of the knowledge on the structure-activity relationship of BAs for FXR, semi-synthetic and synthetic molecules have been generated to obtain more selective and powerful FXR activators than BAs. This article is part of a Special Issue entitled: Linking transcription to physiology in lipodomics. PMID- 25139563 TI - New and unusual forms of calcium oxalate raphide crystals in the plant kingdom. AB - Calcium oxalate crystals in higher plants occur in five major forms namely raphides, styloids, prisms, druses and crystal sand. The form, shape and occurrence of calcium oxalate crystals in plants are species- and tissue specific, hence the presence or absence of a particular type of crystal can be used as a taxonomic character. So far, four different types of needle-like raphide crystals have been reported in plants. The present work describes two new and unusual forms of raphide crystals from the tubers of Dioscorea polystachya- six-sided needles with pointed ends (Type V) and four-sided needles with beveled ends (Type VI). Both of these new types of needles are distinct from the other four types by each having a surrounding membrane that envelopes a bundle of 10-20 closely packed thin crystalline sheets. The previously known four types of needles have solid or homogenous crystalline material, surrounded by a membrane or lamellate sheath called a crystal chamber. Only the Type VI crystals have beveled ends and the needles of the other five types have pointed ends. PMID- 25139562 TI - Protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome. AB - Acute inflammatory responses are protective, yet without timely resolution can lead to chronic inflammation and organ fibrosis. A systems approach to investigate self-limited (self-resolving) inflammatory exudates in mice and structural elucidation uncovered novel resolution phase mediators in vivo that stimulate endogenous resolution mechanisms in inflammation. Resolving inflammatory exudates and human leukocytes utilize DHA and other n-3 EFA to produce three structurally distinct families of potent di- and trihydroxy containing products, with several stereospecific potent mediators in each family. Given their potent and stereoselective picogram actions, specific members of these new families of mediators from the DHA metabolome were named D-series resolvins (Resolvin D1 to Resolvin D6), protectins (including protectin D1 neuroprotectin D1), and maresins (MaR1 and MaR2). In this review, we focus on a) biosynthesis of protectins and maresins as anti-inflammatory-pro-resolving mediators; b) their complete stereochemical assignments and actions in vivo in disease models. Each pathway involves the biosynthesis of epoxide-containing intermediates produced from hydroperoxy-containing precursors from human leukocytes and within exudates. Also, aspirin triggers an endogenous DHA metabolome that biosynthesizes potent products in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT (NPD1/PD1)]. Identification and structural elucidation of these new families of bioactive mediators in resolution has opened the possibility of diverse patho physiologic actions in several processes including infection, inflammatory pain, tissue regeneration, neuroprotection-neurodegenerative disorders, wound healing, and others. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". PMID- 25139564 TI - Successful transplantation of kidney allografts in sensitized rats after syngeneic hematopoietic stem cell transplantation and fludarabine. AB - Current methods to remove donor-specific HLA antibody (DSA) from sensitized patients remain imperfect. We tested novel approaches to desensitization using an animal model of allogeneic sensitization with skin grafts from dark agouti (DA) to Lewis rats. At the peak IgG alloantibody response we transplanted DA kidneys into nephrectomized Lewis recipients (n = 6) and all died within 10 days from antibody-mediated rejection (AMR). Allogeneic hematopoietic stem cell transplants (HSCT) from DA donors failed to engraft after lethal or sub-lethal irradiation. Sensitized rats given lethal irradiation plus syngeneic green fluorescent protein (GFP) + HSCT had repopulation of blood, spleen, thymus and lymph nodes by GFP+ cells. At 2 months after HSCT, serum DSA levels were reduced 60-70% and DSA (IgG) production in cultured splenocytes was also significantly decreased. However, there was only a modest improvement in graft survival from an average of 6.5 to 13.9 (n = 9) days. Adding seven daily doses of fludarabine to the preconditioning regimen resulted in long-term survival (>90 days) in 7 out of 10 rat kidney allografts. We conclude that syngeneic HSCT performed after preconditioning with irradiation and fludarabine can reduce DSA, prevent DSA rebound and AMR, enabling successful transplantation in animals with strong antibody reactivity to the donor MHC. PMID- 25139565 TI - Fragment-based identification and optimization of a class of potent pyrrolo[2,1 f][1,2,4]triazine MAP4K4 inhibitors. AB - MAP4K4 has been shown to regulate key cellular processes that are tied to disease pathogenesis. In an effort to generate small molecule MAP4K4 inhibitors, a fragment-based screen was carried out and a pyrrolotriazine fragment with excellent ligand efficiency was identified. Further modification of this fragment guided by X-ray crystal structures and molecular modeling led to the discovery of a series of promising compounds with good structural diversity and physicochemical properties. These compounds exhibited single digit nanomolar potency and compounds 35 and 44 achieved good in vivo exposure. PMID- 25139566 TI - Synthesis of N-glycan units for assessment of substrate structural requirements of N-acetylglucosaminyltransferase III. AB - N-Acetylglucosaminyltransferase (GnT) III is a glycosyltransferase which produces bisected N-glycans by transferring GlcNAc to the 4-position of core mannose. Bisected N-glycans are involved in physiological and pathological processes through the functional regulation of their carrier proteins. An understanding of the biological functions of bisected glycans will be greatly accelerated by use of specific inhibitors of GnT-III. Thus far, however, such inhibitors have not been developed and even the substrate-binding mode of GnT-III is not fully understood. To gain insight into structural features required of the substrate, we systematically synthesized four N-glycan units, the branching parts of the bisected and non-bisected N-glycans. The series of syntheses were achieved from a common core trimannose, giving bisected tetra- and hexasaccharides as well as non bisected tri- and pentasaccharides. A competitive GnT-III inhibition assay using the synthetic substrates revealed a vital role for the Manbeta(1-4)GlcNAc moiety. In keeping with previous reports, GlcNAc at the alpha1,3-branch is also involved in the interaction. The structural requirements of GnT-III elucidated in this study will provide a basis for rational inhibitor design. PMID- 25139567 TI - A specific cytochrome P450 hydroxylase in herboxidiene biosynthesis. AB - The anti-cholesterol natural product herboxidiene is synthesized by a noniterative modular polyketide synthase (HerB, HerC and HerD) and three tailoring enzymes (HerE, HerF and HerG) in Streptomyces chromofuscus A7847. In this work, the putative monooxygenase HerG was expressed in Escherichia coli and the purified enzyme was subjected to biochemical studies. It was identified as a cytochrome P450 enzyme responsible for the stereospecific hydroxylation at C-18. This enzyme is highly substrate-specific as it efficiently hydroxylates 18-deoxy 25-demethyl-herboxidiene, but showed no activity towards 18-deoxy-herboxidiene. The kcat/Km value for the HerG-catalyzed hydroxylation of 18-deoxy-25-demethyl herboxidiene was determined to be 1669.70+/-47.36 M(-1) s(-1). In vitro co reaction of HerG with the methyltransferase HerF and analysis of the product formation in S. chromofuscus A7847 revealed that the biosynthetic intermediate 18 deoxy-25-demethyl-herboxidiene is successively hydroxylated at C-18 by HerG and methylated at 17-OH to yield the final product herboxidiene. The minor metabolite 18-deoxy-hereboxidiene is a byproduct of the biosynthetic pathway. PMID- 25139568 TI - Synthesis, biological evaluation and molecular modeling study of 2-(1,3,4 thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class of DHFR inhibitors. AB - A new series of 2-(1,3,4-thiadiazolyl- or 4-methyl-thiazolyl)thio-6-substituted quinazolin-4-one analogs was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 29, 34, and 39 proved to be the most active DHFR inhibitors with IC50 values range of 0.1 0.6 MUM. Compounds 28, 31 and 33 showed remarkable broad-spectrum antimicrobial activity comparable to the known antibiotic Gentamicin. Compounds 26, 33, 39, 43, 44, 50, 55 and 63 showed broad spectrum antitumor activity with GI values range of 10.1-100%. Molecular modeling study concluded that recognition with key amino acid Glu30, Phe31 and Phe34 is essential for binding. ADMET properties prediction of the active compounds suggested that compounds 29 and 34 could be orally absorbed with diminished toxicity. PMID- 25139569 TI - Synthesis, biological evaluation and SAR analysis of O-alkylated analogs of quercetin for anticancer. AB - O-Alkylated quercetin analogs were synthesized and their anticancer activities were assessed by a high-throughout screening (HTS) method. The structure-activity relationships (SAR) showed that introduction of long alkyl chain such as propyl group at the C-3 OH position or short alkyl chain such as ethyl group at the C-4' OH position were very important for keeping inhibitory activities against the 16 cancer cell lines. Furthermore, when the two n-butyl groups were introduced into the C-3, C-7 or C-4', C-7 positions, the anticancer activity was enhanced. PMID- 25139570 TI - Synthesis and structure-activity relationships of PI3K/mTOR dual inhibitors from a series of 2-amino-4-methylpyrido[2,3-d]pyrimidine derivatives. AB - Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway by PI3K/mTOR dual inhibitors provides a promising new approach to the treatment of cancers. In this Letter, we identified structurally novel and potent PI3K/mTOR dual inhibitors from a series of 2-amino 4-methylpyrido[2,3-d]pyrimidine derivatives. Their synthesis and structure activity relationships are reported. PMID- 25139571 TI - Identification of cytidine 2',3'-cyclic monophosphate and uridine 2',3'-cyclic monophosphate in Pseudomonas fluorescens pfo-1 culture. AB - Cytidine 2',3'-cyclic monophosphate (2',3'-cCMP) and uridine 2',3'-cyclic monophosphate (2',3'-cUMP) were isolated from Pseudomonas fluorescens pfo-1 cell extracts by semi-preparative reverse phase HPLC. The structures of the two compounds were confirmed by NMR and mass spectroscopy against commercially available authentic samples. Concentrations of both intracellular and extracellular 2',3'-cCMP and 2',3'-cUMP were determined. Addition of 2',3'-cCMP and 2',3'-cUMP to P. fluorescens pfo-1 culture did not significantly affect the level of biofilm formation in static liquid cultures. PMID- 25139572 TI - Palladium-templated subcomponent self-assembly of macrocycles, catenanes, and rotaxanes. AB - The reaction of 2,6-diformylpyridine with diverse amines and Pd(II) ions gave rise to a variety of metallosupramolecular species, in which the Pd(II) ion is observed to template a tridentate bis(imino)pyridine ligand. These species included a mononuclear complex as well as [2+2] and [3+3] macrocycles. The addition of pyridine-containing macrocyclic capping ligands allows for topological complexity to arise, thereby enabling the straightforward preparation of structures that include a [2]catenane, a [2]rotaxane, and a doubly threaded [3]rotaxane. PMID- 25139573 TI - The BODE index, a multidimensional grading system, reflects impairment of right ventricle functions in patients with chronic obstructive pulmonary disease: a speckle-tracking study. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is not only characterized by chronic airflow limitation, but is also a systemic disease. There is no information about alterations in right ventricle (RV) functions precipitated by systemic manifestations of COPD. OBJECTIVES: We aimed to evaluate the relationship between the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index that evaluates systemic manifestations of COPD and RV functions by means of 2-dimensional speckle-tracking echocardiography (2D-STE) in COPD patients. METHODS: The study involved 135 COPD patients and 37 control subjects. All patients underwent 2D-STE, pulmonary function tests and 6-min walk tests, and were divided into quartiles according to their calculated BODE index score. RESULTS: COPD patients had impaired RV and left-ventricle diastolic functions compared to controls. There was a decreasing trend from quartile 1 (Q1) to Q4 in RV functional parameters, i.e., RV free wall strain (RVFW-S, p < 0.001), tricuspid annular plane systolic excursion (p < 0.001), systolic myocardial velocity (p < 0.001), RV fractional area change (p < 0.001), RV myocardial performance index (p < 0.001) and pulmonary artery systolic pressure (p < 0.001). The transmitral Doppler E wave/lateral mitral annular tissue Doppler E wave ratio was similar in the 4 BODE index quartiles (p = 0.159). Multivariate analysis was performed to find independent predictors of decreased RVFW-S (<=19.06), and the BODE index (in quartiles; OR 4.61 and 95% CI 1.85-11.63) was found to be an independent predictor. In a partial correlation analysis adjusted for forced expiratory volume in 1s % predicted, RVFW-S was correlated with the 6-min walk distance (r = 0.498). CONCLUSION: The BODE index, which can be easily evaluated in office settings, may provide information about reduced RV functions as well as guiding treatment and helping to predict prognosis in COPD patients. PMID- 25139574 TI - Postoperative radiation therapy for extramammary Paget's disease. AB - BACKGROUND: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that is usually treated with surgery. Patients with positive surgical margins require adjuvant therapy, but there have been few reports on the use of radiation therapy. OBJECTIVES: To investigate the effectiveness of postoperative radiation therapy in EMPD. MATERIALS AND METHODS: Twenty-one patients with EMPD involving the genitalia underwent radiation therapy as adjuvant therapy after surgery. Ten patients had inguinal lymph node involvement before radiation therapy, but none had distant metastases. A median total dose of 59.4 Gy (range, 45-64.8 Gy) was delivered to the tumour bed in 30 fractions (range, 23-36 fractions). RESULTS: At a median follow-up period of 38 months, all patients had local control. However, six patients had developed distant metastases 6-43 months after radiation therapy. The distant metastasis-free rates were 66% at 3 years and 55% at 5 years. Inguinal lymph node involvement was a significant risk factor for distant metastases. Four patients died 33-58 months after irradiation; the causes of death were tumour progression in three patients and infectious pneumonia in one. The overall and cause-specific survival rates were both 92% at 3 years, and 62% and 71% at 5 years, respectively. No therapy-related toxicities of grade >= 3 were observed. CONCLUSIONS: Postoperative radiation therapy is safe and effective in maintaining local control in patients with EMPD. PMID- 25139575 TI - Electrified emotions: Modulatory effects of transcranial direct stimulation on negative emotional reactions to social exclusion. AB - Social exclusion, ostracism, and rejection can be emotionally painful because they thwart the need to belong. Building on studies suggesting that the right ventrolateral prefrontal cortex (rVLPFC) is associated with regulation of negative emotions, the present experiment tests the hypothesis that decreasing the cortical excitability of the rVLPFC may increase negative emotional reactions to social exclusion. Specifically, we applied cathodal transcranial direct current stimulation (tDCS) over the rVLPFC and predicted an increment of negative emotional reactions to social exclusion. In Study 1, participants were either socially excluded or included, while cathodal tDCS or sham stimulation was applied over the rVLPFC. Cathodal stimulation of rVLPFC boosted the typical negative emotional reaction caused by social exclusion. No effects emerged from participants in the inclusion condition. To test the specificity of tDCS effects over rVLPFC, in Study 2, participants were socially excluded and received cathodal tDCS or sham stimulation over a control region (i.e., the right posterior parietal cortex). No effects of tDCS stimulation were found. Our results showed that the rVLPFC is specifically involved in emotion regulation and suggest that cathodal stimulation can increase negative emotional responses to social exclusion. PMID- 25139576 TI - Predicting fetal lung maturity using the fetal pulmonary artery Doppler wave acceleration/ejection time ratio. AB - OBJECTIVE: To determine whether the acceleration/ejection time ratio of the fetal main pulmonary artery Doppler waveform (PATET) can accurately predict the results of fetal lung maturity testing in amniotic fluid. METHODS: We prospectively studied pregnant women attending our ultrasound unit for clinically indicated fetal lung maturity testing. An ultrasound examination that included measurement of the PATET was performed before the results of the amniocentesis were reported. The results of the PATET and the surfactant/albumin ratio were compared, and a receiver operating characteristic curve was used to determine the PATET cutoff with the optimal sensitivity and specificity for predicting surfactant/albumin ratio results. p < 0.05 was considered statistically significant. RESULTS: Forty three patients were included in this study. The receiver operating characteristic curve demonstrated that a PATET cutoff of 0.3149 provided a specificity of 93% (95% CI 77-98%), a sensitivity of 73% (95% CI 48-89%), a negative predictive value of 87% (95% CI 70-95%), and a positive predictive value of 85% (95% CI 58 96%) for predicting immature surfactant/albumin ratio results. CONCLUSION: The PATET may provide a noninvasive means of determining fetal lung maturity with acceptable levels of sensitivity, specificity, and predictive values. PMID- 25139577 TI - Nestin expression and glial response in the hippocampus of mice after trimethyltin treatment. AB - Nestin is a protein of embryonic intermediate filaments expressed by multipotent neural stem cells. In the present study, the nestin expression pattern in the mouse hippocampus 1, 2, 3, 4, and 8 days after treatment with trimethyltin (TMT) was examined to explore the possible role played by nestin in chemically induced hippocampal injury. TMT treatment (2.5mg/kg, intraperitoneally) selectively injured the dentate gyrus (DG) of the mouse hippocampus. The level of hippocampal mRNA encoding nestin increased significantly 2 and 3 days post-treatment and thereafter decreased (at 4 and 8 days post-treatment). The level of nestin protein significantly increased 2 - 4 days post-treatment, particularly in the injured region of the DG, and predominantly in glial fibrillary acidic protein positive astrocytes in the hippocampal DG. Ki67-positive proliferating cells were increased following TMT treatment and co-localized with nestin-positive reactive astrocytes. Thus, we suggest that nestin contributes to remodeling of the chemically injured DG via glial scar formation and the alteration of neurogenesis. PMID- 25139578 TI - Longitudinal resting state fMRI analysis in healthy controls and premanifest Huntington's disease gene carriers: a three-year follow-up study. AB - BACKGROUND: We previously demonstrated that in the premanifest stage of Huntington's disease (preHD), a reduced functional connectivity exists compared to healthy controls. In the current study, we look at possible changes in functional connectivity occurring longitudinally over a period of 3 years, with the aim of assessing the potential usefulness of this technique as a biomarker for disease progression in preHD. METHODS: Twenty-two preHD and 17 healthy control subjects completed resting state functional magnetic resonance imaging (fMRI) scans in two visits with 3 years in between. Differences in resting state connectivity were examined for eight networks of interest using FSL with three different analysis types: a dual regression method, region of interest approach, and an independent component analysis. To evaluate a possible combined effect of gray matter volume change and the change in blood oxygenation level dependent signal, the analysis was performed with and without voxel-wise correction for gray matter volume. To evaluate possible correlations between functional connectivity change and the predicted time to disease onset, the preHD group was classed as preHD-A if >=10.9 years and preHD-B if <10.9 years from predicted disease onset. Possible correlations between burden of pathology score and functional connectivity change in preHD were also assessed. Finally, longitudinal change in whole brain and striatal volumetric measures was assessed in the studied cohort. RESULTS: Longitudinal analysis of the resting state-fMRI (RS fMRI) data revealed no differences in the degree of connectivity change between the groups over a period of 3 years, though a significantly higher rate of striatal atrophy was found in the preHD group compared to controls in the same period. DISCUSSION: Based on the results found in this study, the provisional conclusion is that RS-fMRI lacks sensitivity in detecting changes in functional connectivity in HD gene carriers prior to disease manifestation over a 3-year follow-up period. PMID- 25139579 TI - Chassis organism from Corynebacterium glutamicum--a top-down approach to identify and delete irrelevant gene clusters. AB - For synthetic biology applications, a robust structural basis is required, which can be constructed either from scratch or in a top-down approach starting from any existing organism. In this study, we initiated the top-down construction of a chassis organism from Corynebacterium glutamicum ATCC 13032, aiming for the relevant gene set to maintain its fast growth on defined medium. We evaluated each native gene for its essentiality considering expression levels, phylogenetic conservation, and knockout data. Based on this classification, we determined 41 gene clusters ranging from 3.7 to 49.7 kbp as target sites for deletion. 36 deletions were successful and 10 genome-reduced strains showed impaired growth rates, indicating that genes were hit, which are relevant to maintain biological fitness at wild-type level. In contrast, 26 deleted clusters were found to include exclusively irrelevant genes for growth on defined medium. A combinatory deletion of all irrelevant gene clusters would, in a prophage-free strain, decrease the size of the native genome by about 722 kbp (22%) to 2561 kbp. Finally, five combinatory deletions of irrelevant gene clusters were investigated. The study introduces the novel concept of relevant genes and demonstrates general strategies to construct a chassis suitable for biotechnological application. PMID- 25139580 TI - Efficacy of interleukin-1 targeting treatments in patients with familial mediterranean Fever. AB - Herein, we reported our experience in colchicine-resistant familial Mediterranean fever (FMF) patients who are treated with anti-interleukin-1 (IL-1) drugs. A retrospective review of medical records of anti-IL-1 recipients was performed. The main clinical characteristics of these patients and the evolution after anti IL-1 were recorded. There were 20 patients (11 male [M] and 9 female [F]). Despite regular colchicine treatment, median number of attacks per month and per year was 1 (1-4) and 12 (4-50), respectively. Twelve patients were receiving anakinra, and eight patients were treated with canakinumab. The number of monthly and yearly attacks after IL-1 treatment was significantly decreased after the biologic agent (p < 0.05). One patient did not respond to the treatment, and one patient developed serious infection during anti-IL-1. We also observed a significant decrease in proteinuria in the amyloidosis complicated FMF patients. Anti-IL-1 targeting drugs seem safe and effective therapies in colchicine resistant FMF. PMID- 25139581 TI - Flavonoids inhibit COX-1 and COX-2 enzymes and cytokine/chemokine production in human whole blood. AB - Cyclooxygenase 2 (COX-2) and the production of cytokines/chemokines are important targets for the modulation of the inflammatory response. Although a large variety of inhibitors of these pathways have been commercialized, some of those inhibitors present severe side effects, governing the search for new molecules, as alternative anti-inflammatory agents. This study was undertaken to study an hitherto not evaluated group of flavonoids, concerning its capacity to inhibit COX-1 and COX-2 enzymes, as well as to inhibit the production of the cytokines and a chemokine, in a complex matrix involved in the systemic inflammatory process, the blood, aiming the establishment of a structure-activity relationship. The results obtained reveal promising flavonoids for the modulation of the inflammatory process, namely the ones presenting a catechol group in B ring, as some flavonoids were able to simultaneously inhibit the production of inflammatory prostaglandin E2 and pro-inflammatory cytokines. PMID- 25139582 TI - Omentin changes following bariatric surgery and predictive links with biomarkers for risk of cardiovascular disease. AB - BACKGROUND: Although no receptor has yet been identified, changes in circulating levels of the adipokine designated as Omentin have been demonstrated in obesity and related comorbidities such as cardiovascular disease, insulin resistance, metabolic syndrome and chronic inflammation. METHODS: Changes in Omentin levels at 1 and 5 days and 6 and 12 months in response to biliopancreatic diversion with duodenal switch bariatric surgery were evaluated, specifically to investigate if changes preceded gain of insulin sensitivity. RESULTS: Pre-operative plasma Omentin was not different between men (n = 18) vs women (n = 48), or diabetic status but correlated with body mass index (BMI). Altogether, Omentin increased as early as 24-h post-surgery, with changes maintained up to 1-year. Fifty-nine percent of subjects increased Omentin >10% by 24-H following surgery (OmentinINC p < 0.0001), while 18% of subjects decreased (OmentinDEC p < 0.0001), with changes maintained throughout one-year. These two groups had comparable age, sex distribution, diabetes, BMI, waist circumference and fat mass, however OmentinDEC had elevated levels of cardiovascular risk markers; homocysteine (p = 0.019), NT proBNP (p = 0.006) and total bilirubin (p = 0.0001) while red blood cell (RBC) count was lower (p = 0.0005) over the one-year period. Omentin levels at 1-DAY also correlated with immune parameters (white blood cell count, % neutrophil, % monocytes, % lymphocytes). CONCLUSION: OmentinDEC at 1 day following surgery may be a marker of cardiovascular "at-risk" group before weight loss or insulin sensitivity restoration. PMID- 25139583 TI - Tissue multifractality and Born approximation in analysis of light scattering: a novel approach for precancers detection. AB - Multifractal, a special class of complex self-affine processes, are under recent intensive investigations because of their fundamental nature and potential applications in diverse physical systems. Here, we report on a novel light scattering-based inverse method for extraction/quantification of multifractality in the spatial distribution of refractive index of biological tissues. The method is based on Fourier domain pre-processing via the Born approximation, followed by the Multifractal Detrended Fluctuation Analysis. The approach is experimentally validated in synthetic multifractal scattering phantoms, and tested on biopsy tissue slices. The derived multifractal properties appear sensitive in detecting cervical precancerous alterations through an increase of multifractality with pathology progression, demonstrating the potential of the developed methodology for novel precancer biomarker identification and tissue diagnostic tool. The novel ability to delineate the multifractal optical properties from light scattering signals may also prove useful for characterizing a wide variety of complex scattering media of non-biological origin. PMID- 25139584 TI - Factors affecting chronic pain and increases of analgesic drug consumption after knee arthroplasty. PMID- 25139585 TI - Pain therapy with high risk: one-sided presentation of the results from the latest phase III study on tanezumab in osteoarthritis pain. PMID- 25139586 TI - Evidence for efficacy of acute treatment of episodic tension-type headache: methodological critique of randomised trials for oral treatments. AB - The International Headache Society (IHS) provides guidance on the conduct of trials for acute treatment of episodic tension-type headache (TTH), a common disorder with considerable disability. Electronic and other searches identified randomised, double-blind trials of oral drugs treating episodic TTH with moderate or severe pain at baseline, or that tested drugs at first pain onset. The aims were to review methods, quality, and outcomes reported (in particular the IHS recommended primary efficacy parameter pain-free after 2 hours), and to assess efficacy by meta-analysis. We identified 58 reports: 55 from previous reviews and searches, 2 unpublished reports, and 1 clinical trial report with results. We included 40 reports of 55 randomised trials involving 12,143 patients. Reporting quality was generally good, with potential risk of bias from incomplete outcome reporting and small size; the 23 largest trials involved 82% of patients. Few trials reported IHS outcomes. The number needed to treat values for being pain free at 2 hours compared with placebo were 8.7 (95% confidence interval [CI] 6.2 to 15) for paracetamol 1000 mg, 8.9 (95% CI 5.9 to 18) for ibuprofen 400mg, and 9.8 (95% CI 5.1 to 146) for ketoprofen 25mg. Lower (better) number needed to treat values were calculated for outcomes of mild or no pain at 2 hours, and patient global assessment. These were similar to values for these drugs in migraine. No other drugs had evaluable results for these patient-centred outcomes. There was no evidence that any one outcome was better than others. The evidence available for treatment efficacy is small in comparison to the size of the clinical problem. PMID- 25139587 TI - Challenges and cautions with small and retrospective postoperative pain genome wide association studies with TAOK3. PMID- 25139588 TI - Affective disturbance associated with premenstrual dysphoric disorder does not disrupt emotional modulation of pain and spinal nociception. AB - In healthy individuals, emotions modulate pain and spinal nociception according to a valence linear trend (ie, pain/nociception is highest during negative emotions and lowest during positive emotions). However, emerging evidence suggests that emotional modulation of pain (but not spinal nociception) is disrupted in fibromyalgia and disorders associated with chronic pain risk (eg, major depression, insomnia). The present study attempted to extend this work and to examine whether women with premenstrual dysphoric disorder (PMDD), a cyclical syndrome associated with debilitating affective symptoms during the late-luteal (premenstrual) phase of the menstrual cycle, is also associated with disrupted emotional modulation of pain. To do so, an affective picture-viewing procedure was used to study emotional modulation of pain and spinal nociception in 14 women with PMDD and 14 control women during mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle (verified by salivary hormone levels and luteinizing hormone tests). At each phase, mutilation, neutral, and erotic pictures were presented to manipulate emotion. During picture viewing, suprathreshold electrocutaneous stimuli were presented to evoke pain and the nociceptive flexion reflex (NFR; a physiological measure of spinal nociception). Statistically powerful linear mixed model analyses confirmed that pictures evoked the intended emotional states in both groups across all menstrual phases. Furthermore, emotion modulated pain and NFR according to a valence linear trend in both groups and across all menstrual phases. Thus, PMDD-related affective disturbance is not associated with a failure to emotionally modulate pain, suggesting that PMDD does not share this pain phenotype with major depression, insomnia, and fibromyalgia. PMID- 25139589 TI - The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study. AB - In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo. The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined by hypersensitivity and preserved small nerve fibre function determined by detailed quantitative sensory testing. Ninety seven patients with peripheral neuropathic pain due to polyneuropathy, surgical or traumatic nerve injury, or postherpetic neuralgia were randomised. The intention-to-treat population comprised 83 patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment and phenotype of 0.7 (95% CI 0.01-1.4, P=0.047). The number needed to treat to obtain one patient with more than 50% pain relief was 6.9 (95% CI 4.2-22) in the total sample, 3.9 (95% CI 2.3-12) in the irritable, and 13 (95% CI 5.3-infinity) in the nonirritable nociceptor phenotype. In conclusion, oxcarbazepine is more efficacious for relief of peripheral neuropathic pain in patients with the irritable vs the nonirritable nociceptor phenotype. PMID- 25139590 TI - Nox2-dependent signaling between macrophages and sensory neurons contributes to neuropathic pain hypersensitivity. AB - Emerging lines of evidence indicate that production of reactive oxygen species (ROS) at distinct sites of the nociceptive system contributes to the processing of neuropathic pain. However, the mechanisms underlying ROS production during neuropathic pain processing are not fully understood. We here detected the ROS generating nicotinamide adenine dinucleotide phosphate oxidase isoform Nox2 in macrophages of dorsal root ganglia (DRG) in mice. In response to peripheral nerve injury, Nox2-positive macrophages were recruited to DRG, and ROS production was increased in a Nox2-dependent manner. Nox2-deficient mice displayed reduced neuropathic pain behavior after peripheral nerve injury, whereas their immediate responses to noxious stimuli were normal. Moreover, injury-induced upregulation of tumor necrosis factor alpha was absent, and activating transcription factor 3 induction was reduced in DRG of Nox2-deficient mice, suggesting an attenuated macrophage-neuron signaling. These data suggest that Nox2-dependent ROS production in macrophages recruited to DRG contributes to neuropathic pain hypersensitivity, underlining the observation that Nox-derived ROS exert specific functions during the processing of pain. PMID- 25139591 TI - Supraspinal TRPV1 modulates the emotional expression of abdominal pain. AB - The transient receptor potential vanilloid receptor type-1 (TRPV1) is critically involved in peripheral nociceptive processes of somatic and visceral pain. However, the role of the capsaicin receptor in the brain regarding visceral pain remains elusive. Here, we studied the contribution of TRPV1 to abdominal pain transmission at different nociceptive pathway levels using TRPV1 knock-out mice, resiniferatoxin-mediated deletion of TRPV1-positive primary sensory neurons, and intracerebral TRPV1 antagonism. We found that constitutive genetic TRPV1 deletion or peripheral TRPV1 deletion reduced acetic acid-evoked abdominal constrictions, without affecting referred abdominal hyperalgesia or allodynia in an acute pancreatitis model of visceral pain. Notably, intracerebral TRPV1 antagonism by SB 366791 significantly reduced chemical and inflammatory spontaneous abdominal nocifensive responses, as observed by reduced expressions of nociceptive facial grimacing, illustrating the affective component of pain. In addition to the established role of cerebral TRPV1 in anxiety, fear, or emotional stress, we demonstrate here for the first time that TRPV1 in the brain modulates visceral nociception by interfering with the affective component of abdominal pain. PMID- 25139592 TI - Dyspneic athlete. AB - Breathing concerns in athletes are common and can be due to a wide variety of pathology. The most common etiologies are exercise-induced bronchoconstriction (EIB) and paradoxic vocal fold movement disorder (PVFMD). Although some patients may have both, PVFMD is often misdiagnosed as EIB, which can lead to unnecessary treatment. The history and physical exam are important to rule out life threatening pulmonary and cardiac causes as well as common conditions such as gastroesophageal reflux disease, sinusitis, and allergic etiologies. The history and physical exam have been shown to be not as vital in diagnosing EIB and PVFMD. Improvement in diagnostic testing with office base spirometry, bronchoprovocation testing, eucapnic voluntary hyperpnea (EVH) and video laryngoscopy are essential in properly diagnosing these conditions. Accurate diagnosis leads to proper management, which is essential to avoid unnecessary testing and save healthcare costs. Also important to the physician treating dyspnea in athletes is knowing regulations on medications, drug testing, and proper documentation needed for certain organizations. The differential diagnosis of dyspnea is broad and is not limited to EIB and PVFMD. Ruling out life threatening cardiac and pulmonary causes with a proper history, physical, and appropriate testing is essential. The purpose of this review is to highlight recent literature on the diagnosis and management of EIB and PVFMD as well as discuss other potential causes for dyspnea in the athlete. PMID- 25139593 TI - Do thrombotic events during endovascular interventions lead to poorer outcomes in patients with severe limb ischemia? AB - INTRODUCTION: Intra-procedural acute thrombosis (IPAT) is a complication of endovascular procedures. We aim to identify risk factors for IPAT and compare the outcomes of patients with or without IPAT. METHODS: Paired T test and chi (2) test were used to identify risk factors and short-term outcomes. Kaplan-Meier survival analysis was used for mid-term outcomes. RESULTS: A total of 228 procedures were performed with 21 IPAT events (9.21%). The odds ratio of Indian patients developing IPAT was 2.8x (95% CI 1.1-7.6). Patients with in-stent occlusion or prior IPAT were 5.6x (95% CI 1.3-24.2) and 5.6x (95% CI 1.3-24.4) more likely to develop an IPAT event. Patients without IPAT had significantly more improvement in mean runoff score (-1.15 +/- 1.31, p < 0.01). The odds of patients with IPAT requiring subsequent endovascular intervention and arterial bypass surgery were 4.2x (95% CI 1.6-10.7) and 7.1x (95% CI 1.9-27.0). There was no significant Kaplan-Meier estimated overall survival or amputation-free survival difference between patients with or without IPAT event. CONCLUSION: Indian ethnicity, in-stent occlusion and previous IPAT were associated with higher risk of IPAT. Even after successful endovascular salvage, patients with IPATs were more likely to require secondary revascularization procedure. Patients with IPATs had no decrease in overall survival or amputation-free survival. PMID- 25139594 TI - Wound debridement optimisation. AB - Wound debridement, the removal of contaminated tissue and senescent cells, is the cornerstone in the care of patients with chronic wounds. PMID- 25139595 TI - Device-related atypical pressure ulcer after cardiac surgery. AB - Medical devices must be closely monitored to prevent harm to patients. Pressure ulcers secondary to medical devices present a significant health burden in terms of length of stay in hospital and cost. Intensivists, anaesthetists and other professionals involved in managing critically ill patients following cardiac surgery need to be aware that pressure ulcers may develop in atypical sites and present at a later stage of the hospital stay. This case report highlights the important issue of device-related pressure ulcers in the cardiac surgical intensive care setting, particularly when the clinical status of the patient may preclude routine assessment and prophylaxis. An algorithm for preventing such pressure ulcers is suggested. PMID- 25139596 TI - The use of immunosuppressive agents in the management of recalcitrant lower limb ulcers. AB - OBJECTIVE: Lower limb ulcers that are resistant to standard forms of treatment place a significant burden on both patients and health services. There is no widely agreed definition of a recalcitrant ulcer but failure to heal following 6 12 months of focused treatment would identify a small group of patients with highly resistant ulceration. We describe a series of patients with recalcitrant ulceration for which immunosuppressive agents have been used. METHODS: This is a case series of 13 patients who underwent immunomodulation therapy for lower limb ulcers at a tertiary referral university hospital. Regimens of immunomodulation used mainly ciclosporin and/or cyclophosphamide, with concurrent antibiotic therapy. Case notes and computer systems were analysed by two reviewers. A patient was deemed to have a success if their ulcer fully healed while on immunomodulation therapy. RESULTS: Over a period of eight years, from 2004-2012, 13 patients underwent immunomodulation therapy. Among these patients there were 18 ulcerated limbs. Ulcer healing occurred in 10 limbs out of 18 (55.6%) and full healing occurred in six patients (46.2%). Ulcers were present for a median of five years (range 2-40 years), with a median diameter of 7.5 cm (range 4-18 cm) before treatment. CONCLUSION: Treatment of truly recalcitrant ulceration can be very frustrating for both the patient and physician, with poor success from more standard forms of treatment. We report experience with immunomodulation therapy that suggests there may be benefit from using this treatment in a subset of patients with this debilitating disease. PMID- 25139597 TI - A novel approach to the treatment of diabetic foot abscesses - a case series. AB - Diabetic foot abscesses are an occasional complication of diabetic foot infections usually involving osteomyelitis and significant soft tissue injury. The standard of care for diabetic foot abscesses is the performance of immediate surgical drainage and debridement. However, this therapeutic mode involves more often than not, some extent of minor amputation and bony loss. With the advent of new therapeutic techniques it may be possible to treat diabetic foot abscesses conservatively. OBJECTIVE: To explore adjunct therapies in the treatment of diabetic foot abscesses in order to avoid extensive surgery, amputation and tissue loss whilst maintaining limb integrity. METHOD AND RESULTS: Between January 2011 and June 2012, six patients with a diabetic foot abscess and osteomyelitis presented at our diabetic foot clinic. They were treated with topical oxygen and the abscesses were drained using PolyMem(r) Wic(r) Silver Rope (PWSR). All patients experienced full recovery and remained disease free during a follow up period of 4-21 months. CONCLUSION: Amputation and the removal of infected bone had once been considered the sole treatment for diabetic foot osteomyelitis. Multiple case series and accumulation of clinical experience has shown otherwise, and nowadays medical management of osteomyelitis is the preferred treatment in select patients. In our study, we present a case series of patients suffering from diabetic foot abscesses treated non-surgically. Hopefully this series will lay the foundation for further data demonstrating the feasibility of a conservative approach for diabetic foot abscesses, which may overcome the infection without requiring amputation. PMID- 25139598 TI - Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-beta expression. AB - OBJECTIVE: Transforming growth factor-beta (TGF-beta) plays an important role in wound healing. Delayed wound healing is a consequence of diabetes, leading to high morbidity and poor quality of life. Momordica charantia (MC) fruit possesses anti-diabetic and wound healing properties. This study aimed to explore the changes in TGF-beta expression in diabetic wounds treated with topical MC fruit extract. METHODS: Fifty-six male Sprague-Dawley rats were divided into a normal control group and five diabetic groups of ten rats each. Intravenous streptozotocin (50mg/kg) was given to induce diabetes in the diabetic groups. Full thickness excision wounds were created on the thoracodorsal region of the animals, and these wounds were then treated with vehicle, MC powder, MC ointment and povidone ointment or ointment base for ten days. Wound healing was determined by the rate of wound closure, total protein content and TGF-beta expression in the wounds, and histological observation. RESULTS: Diabetic groups showed delayed wound closure rates compared to the control group. The wound closure rate in the MC ointment group was significantly faster than that of the untreated diabetic group (p<0.05). The MC ointment group also showed intense TGF-beta expression and a high level of total protein content. CONCLUSION: MC ointment has a promising potential for use as an alternative topical medication for diabetic wounds. This work has shown that it accelerates wound healing in diabetic rats, and it is suggested here that this occurs by enhancing TGF-beta expression. Further work is recommended to explore this effect. PMID- 25139599 TI - Effects of SertaSil on wound healing in the rat. AB - OBJECTIVE: SertaSil is a novel product for the topical management of wound exudate. The purpose of this study was to evaluate the ability of SertaSil to promote wound healing in a pre-clinical wound model. METHODS: An aseptic wound was induced in rats by administering 1ml 10% calcium chloride solution into the subcutaneous layer under local anaesthesia. Following opening of the abscess, animals were divided into a control group (no treatment) and either SertaSil or Gentaxane, which were applied topically to the wound every 24 hours until a clean wound was achieved, that is, free from necrosis, pus and fibrinogenous thickenings. RESULTS: Rats (n=15 per group) receiving SertaSil reached the clean wound stage in 3.0 +/- 0.4 days compared to 7.0 +/- 0.4 days for Gentaxane and 10.0 +/- 0.4 days for the control. Time to wound closure was 13.9 +/- 0.3 days for SertaSil, 18.7 +/- 0.6 days for Gentaxane, and 23.0 +/- 0.4 days for the control. The surface area of the wounds were measured at day 1 and day 13. At day 1, the wound surface areas (mm2) were similar in all three groups (157.4 +/- 8.9), but at day 13 the SertaSil group had significantly smaller wound areas (5.2 +/- 1.7) compared to the Gentaxane (38.0 +/- 1.5) and control groups (95.7 +/- 11.3). The study was conducted in young rats that are still growing and gaining weight. At day 19, only the rats receiving SertaSil exhibited a weight increase (271 +/- 5 g) indicating good recovery, whereas rats receiving Gentaxane did not gain weight (249 +/- 5 g) and rats in the control group lost weight (242 +/- 16 g). CONCLUSION: The study found that SertaSil reduced the time to reaching a clean wound by 60% compared to Gentaxane and promoted faster wound closure and better recovery. These findings suggest that SertaSil may be valuable for use in the treatment of wounds in patients. PMID- 25139600 TI - Adhesion of the ulcerative pathogen Mycobacterium ulcerans to DACC-coated dressings. AB - OBJECTIVE: Mycobacterium ulcerans is the causative agent of Buruli ulcer disease, the third most common mycobacteriosis after tuberculosis and leprosy and an emerging public health threat in sub-Saharan Africa. The bacteria produce a diffusible cytotoxin called mycolactone, which triggers the formation of necrotic lesions in cutaneous and subcutaneous tissues. The principal aim of this study was to characterise the cell surface hydrophobicity of Mycobacterium ulcerans and determine if bacteria bind to dialkyl carbamoyl chloride (DACC)-coated dressings through hydrophobic interactions in vitro. Since mycolactone displays hydrophobic groups, a secondary aim was to compare mycolactone binding to hydrophobic and standard dressings. METHODS: We used hydrophobic interaction chromatography to evaluate the cell surface hydrophobicity of Mycobacterium ulcerans, compared to that of other microorganisms colonising wounds. The binding of Mycobacterium ulcerans bacteria to DACC-coated and control dressings was then assessed quantitatively by measurement of microbial adenosine triphosphate (ATP), while that of mycolactone was evaluated by fluorescence spectroscopy. RESULTS: Compared to Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, Mycobacterium ulcerans displayed the highest cell surface hydrophobicity, irrespective of the bacterial production of mycolactone. Mycobacterium ulcerans bacteria bound to DACC-coated dressings [corrected] better than untreated controls. Mycolactone did not bind stably to hydrophobic, nor standard dressings, in the conditions tested. CONCLUSION: Retention of Mycobacterium ulcerans and other wound pathogens to DACC-coated dressings may help reduce the bacterial load in Buruli ulcers and thereby improve healing. Dressings efficiently capturing mycolactone may bring an additional clinical benefit, by accelerating the elimination of the toxin during the course of antibiotic treatment. PMID- 25139601 TI - Biofilms in wounds: the chicken or the egg? PMID- 25139602 TI - Issues, following cancer treatment, that patients would like to discuss at their review consultation. PMID- 25139605 TI - The poet, his poem, and the surgeon: the stories behind the enduring appeal of Invictus. PMID- 25139606 TI - Effect of instructor feedback on skills retention after laparoscopic simulator training: follow-up of a randomized trial. AB - BACKGROUND: Instructor feedback reduces the number of repetitions and time to reach proficiency during laparoscopic simulator training. The objective of this study was to examine the effect of instructor feedback on long-term skill retention. METHODS: A 6-month follow-up of a randomized trial. Participants were surgical novices (medical students). All participants (n = 99) initially practiced a laparoscopic salpingectomy on the LapSim virtual reality simulator to proficiency. The intervention group could request instructor feedback, whereas the control group could not. After 6 months, the participants (n = 65) practiced on the simulator until they reached proficiency again. The primary outcomes were the total time and the number of repetitions. RESULTS: Initially, the intervention group used significantly fewer repetitions (29 vs 65, p < 0.0005) and less total training time (162 vs 342 min, p < 0.0005) than the control group to reach the proficiency level. At follow-up, both the groups used an equal number of repetitions (21 vs 20, p = 0.72) and time (83 vs 73 min, p = 0.37) to reach the same proficiency level. CONCLUSIONS: Instructor feedback during proficiency-based laparoscopic simulator training does not affect the long-term retention of skills. PMID- 25139607 TI - Measuring general surgery residents' communication skills from the patient's perspective using the Communication Assessment Tool (CAT). AB - OBJECTIVE: The Communication Assessment Tool (CAT) has been used and validated to assess Family and Emergency Medicine resident communication skills from the patient's perspective. However, it has not been previously reported as an outcome measure for general surgery residents. The purpose of this study is to establish initial benchmarking data for the use of the CAT as an evaluation tool in an osteopathic general surgery residency program. Results are analyzed quarterly and used by the program director to provide meaningful feedback and targeted goal setting for residents to demonstrate progressive achievement of interpersonal and communication skills with patients. DESIGN: The 14-item paper version of the CAT (developed by Makoul et al. for residency programs) asks patients to anonymously rate surgery residents on discrete communication skills using a 5-point rating scale immediately after the clinical encounter. Results are reported as the percentage of items rated as "excellent" (5) by the patient. SETTING: The setting is a hospital-affiliated ambulatory urban surgery office staffed by the residency program. PARTICIPANTS: Participants are representative of adult patients of both sexes across all ages with diverse ethnic backgrounds. They include preoperative and postoperative patients, as well as those needing diagnostic testing and follow-up. RESULTS: Data have been collected on 17 general surgery residents from a single residency program representing 5 postgraduate year levels and 448 patient encounters since March 2012. The reliability (Cronbach alpha) of the tool for surgery residents was 0.98. The overall mean percentage of items rated as excellent was 70% (standard deviations = 42%), with a median of 100%. CONCLUSIONS: The CAT is a useful tool for measuring 1 facet of resident communication skills-the patient's perception of the physician-patient encounter. The tool provides a unique and personalized outcome measure for identifying communication strengths and improvement opportunities, allowing residents to receive specific feedback and mentoring by program directors. PMID- 25139608 TI - Fast redox-triggered shuttling motions in a copper rotaxane based on a phenanthroline-terpyridine conjugate. AB - Fast shuttling motions in solution have been observed by cyclic voltammetry in a Cu(I/II)-based [2] rotaxane. In the reported system, the different coordination preferences of both copper oxidation states are exploited to promote the electrochemically-triggered gliding of the ring from a tetra to a pentacoordinated site and vice versa. The thread of this rotaxane consists of a tridentate 2,2':6',2''-terpyridine chelating unit directly bonded through its 5 position to the 3-position of the bidentate 1,10-phenanthroline unit. This distribution reduces to a minimum the distance between the two coordination sites and lessens the congestion around the tetrahedral environment. These two factors have been demonstrated to highly increase the kinetics of the switching process. In addition, the electrochemical experiments carried out in different solvent mixtures evidenced the influence of the solvent on the shuttling mechanism. PMID- 25139609 TI - Insulin treatment guided by subcutaneous continuous glucose monitoring compared to frequent point-of-care measurement in critically ill patients: a randomized controlled trial. AB - INTRODUCTION: Glucose measurement in intensive care medicine is performed intermittently with the risk of undetected hypoglycemia. The workload for the ICU nursing staff is substantial. Subcutaneous continuous glucose monitoring (CGM) systems are available and may be able to solve some of these issues in critically ill patients. METHODS: In a randomized controlled design in a mixed ICU in a teaching hospital we compared the use of subcutaneous CGM with frequent point of care (POC) to guide insulin treatment. Adult critically ill patients with an expected stay of more than 24 hours and in need of insulin therapy were included. All patients received subcutaneous CGM. CGM data were blinded in the control group, whereas in the intervention group these data were used to feed a computerized glucose regulation algorithm. The same algorithm was used in the control group fed by intermittent POC glucose measurements. Safety was assessed with the incidence of severe hypoglycemia (<2.2 mmol/L), efficacy with the percentage time in target range (5.0 to 9.0 mmol/L). In addition, we assessed nursing workload and costs. RESULTS: In this study, 87 patients were randomized to the intervention and 90 to the control group. CGM device failure resulted in 78 and 78 patients for analysis. The incidence of severe glycemia and percentage of time within target range was similar in both groups. A significant reduction in daily nursing workload for glucose control was found in the intervention group (17 versus 36 minutes; P <0.001). Mean daily costs per patient were significantly reduced with EUR 12 (95% CI -32 to -18, P = 0.02) in the intervention group. CONCLUSIONS: Subcutaneous CGM to guide insulin treatment in critically ill patients is as safe and effective as intermittent point-of-care measurements and reduces nursing workload and daily costs. A new algorithm designed for frequent measurements may lead to improved performance and should precede clinical implementation. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01526044. Registered 1 February 2012. PMID- 25139610 TI - Rituximab in the treatment of autoimmune haemolytic anaemia. AB - Rituximab is a B-cell depleting monoclonal antibody that is gaining popularity as an effective therapy for many autoimmune cytopenias. This article systematically evaluates its therapeutic efficacy in the treatment of different types of autoimmune haemolytic anaemia. We conclude that there is sufficient evidence to recommend it as a second line therapy for warm autoimmune haemolytic anaemia (wAIHA) either as monotherapy or combined therapy. Evidence from a single randomized controlled trial suggests that it may also be more efficacious as first line therapy in combination with steroids than steroids alone. A fewer number of studies have assessed its role in cold autoimmune haemolytic anaemia (cAIHA) and cold agglutinin disease (CAD) with success rates varying from 45-66%. In the absence of alternative definitive therapy, rituximab should be considered for patients with symptomatic CAD and significant haemolysis. Case reports of its efficacy in mixed autoimmune haemolytic anaemias are available but evidence from case series or larger cohorts are nonexistent. PMID- 25139611 TI - Density functional studies on (NCH)n azagraphane: activated surface for organocatalysis. AB - Quantum chemical analysis shows aza-graphane isomers, with alternate C-H and N: sites as ideal organocatalysts; their kinetic stability arises from the tertiary orthoamide. DFT calculations give split-off bands originating from nitrogen lone pairs with substantial mixing of hydrogen, indicating an optimal balance between nitrogen basicity and C-H activation through the anomeric effect. PMID- 25139612 TI - Implementation of evidence-based HIV interventions for young adult African American women in church settings. AB - OBJECTIVE: To assess the barriers and facilitators to using African American churches as sites for implementation of evidence-based HIV interventions among young African American women. DESIGN: Mixed methods cross-sectional design. SETTING: African American churches in Philadelphia, PA. PARTICIPANTS: 142 African American pastors, church leaders, and young adult women ages 18 to 25. METHODS: Mixed methods convergent parallel design. RESULTS: The majority of young adult women reported engaging in high-risk HIV-related behaviors. Although church leaders reported willingness to implement HIV risk-reduction interventions, they were unsure of how to initiate this process. Key facilitators to the implementation of evidence-based interventions included the perception of the leadership and church members that HIV interventions were needed and that the church was a promising venue for them. A primary barrier to implementation in this setting is the perception that discussions of sexuality should be private. CONCLUSION: Implementation of evidence-based HIV interventions for young adult African American women in church settings is feasible and needed. Building a level of comfort in discussing matters of sexuality and adapting existing evidence-based interventions to meet the needs of young women in church settings is a viable approach for successful implementation. PMID- 25139613 TI - Preparation and hydrosilylation activity of a molybdenum carbonyl complex that features a pentadentate bis(imino)pyridine ligand. AB - Attempts to prepare low-valent molybdenum complexes that feature a pentadentate 2,6-bis(imino)pyridine (or pyridine diimine, PDI) chelate allowed for the isolation of two different products. Refluxing Mo(CO)6 with the pyridine substituted PDI ligand, (PyEt)PDI, resulted in carbonyl ligand substitution and formation of the respective bis(ligand) compound ((PyEt)PDI)2Mo (1). This complex was investigated by single-crystal X-ray diffraction, and density functional theory calculations indicated that 1 possesses a Mo(0) center that back-bonds into the pi*-orbitals of the unreduced PDI ligands. Heating an equimolar solution of Mo(CO)6 and the phosphine-substituted PDI ligand, (Ph2PPr)PDI, to 120 degrees C allowed for the preparation of ((Ph2PPr)PDI)Mo(CO) (2), which is supported by a kappa(5)-N,N,N,P,P-(Ph2PPr)PDI chelate. Notably, 1 and 2 have been found to catalyze the hydrosilylation of benzaldehyde at 90 degrees C, and the optimization of 2-catalyzed aldehyde hydrosilylation at this temperature afforded turnover frequencies of up to 330 h(-1). Considering additional experimental observations, the potential mechanism of 2-mediated carbonyl hydrosilylation is discussed. PMID- 25139614 TI - Low-grade albuminuria associated with brachial-ankle pulse wave velocity in young adults with type 2 diabetes mellitus in China. AB - BACKGROUND: Cardiovascular disease is prevalent in type 2 diabetics, and microalbuminuria is associated with cardiovascular disease morbidity. We aimed to investigate the potential association between low-grade albuminuria and arterial stiffness in patients with type 2 diabetes. METHODS: Between 2009 and 2013, a retrospective study was performed in 578 patients with type 2 diabetes (339 male patients and 239 female patients) with normal urinary albumin-to-creatinine ratios (ACRs; <30 mg/g) from Fuzhou, China. Patients were stratified into tertiles based on urinary ACR levels (lowest tertile, urinary ACR < 4.8 mg/g; highest tertile, urinary ACR >= 20.1 mg/g). Arterial stiffness was measured via brachial-ankle pulse wave velocity. RESULTS: Brachial-ankle pulse wave velocity, age, duration of diabetes, systolic blood pressure and pulse wave velocity progressively increased across all urinary albumin-to-creatinine ratio tertiles (p < 0.05). Patients in the second and the highest tertiles had significantly elevated pulse wave velocity [114.6 mm/s (95% CI = 36.8-192.4) and 209.4 mm/s (95% CI = 131.8-286.9)], p = 0.004 and 0.000] compared with those in the lowest ACR tertile. The association between ACR and elevated pulse wave velocity still persisted in patients younger than 65 years of age and those with diabetes <10 years, conferring 45 or 51% greater risk of elevated pulse wave velocity (OR = 1.451; 95% CI = 1.119-1.881; p = 0.005 or OR = 1.515; 95% CI = 1.167-1.966; p = 0.0018) with each ACR tertile increment. Each ACR tertile increment conferred 31.7% higher risk of increased pulse wave velocity (OR = 1.317; 95% CI = 1.004 1.729; p = 0.0468). CONCLUSIONS: Patients with type 2 diabetes with urinary albumin excretion in the upper normal range were still at risk for target organ damage. Low-grade albuminuria might be an early marker for the detection of arterial stiffness in patients with type 2 diabetes, especially in younger patients with type 2 diabetes with shorter durations of disease. PMID- 25139615 TI - Expression and clinical significance of ATP-binding cassette transporter 1 in serum and placental tissue in Chinese patients with preeclampsia. AB - AIM: To investigate the expression and clinical significance of ATP-binding cassette transporter 1 (ABCA1) in pregnant women with preeclampsia (PE). METHODS: 52 pregnant women with PE who were admitted for delivery were enrolled in the study, while 30 normal pregnant inpatients were chosen as controls. Blood lipid and serum ABCA1 concentrations were assayed by enzymatic analysis and ELISA, respectively, and the expression of the ABCA1 gene and its encoded protein were detected and quantified by RT-PCR and Western blotting. RESULTS: In the study group, blood lipid levels were significantly higher than those in the control group (p < 0.01), while the ABCA1 gene and its encoded protein expression in both serum and placental tissue were lower than that of controls. These differences were highly correlated with disease severity (p < 0.05). In PE patients, serum ABCA1 concentration was positively correlated with ABCA1 protein expression in placental tissue (r = 0.384, p < 0.01) and high-density lipoprotein level (r = 0.318, p < 0.05), but negatively correlated with low-density lipoprotein level (r = -0.279, p < 0.05). CONCLUSION: In PE women, expression of ABCA1 was decreased, suggesting that ABCA1 may play an important role in onset of PE by altering blood lipid metabolism. PMID- 25139616 TI - JLK1486, a N,N-[(8-hydroxyquinoline)methyl]-substituted benzylamine analogue, inhibits melanoma proliferation and induces autophagy. AB - OBJECTIVES: To investigate anti-proliferatory activity of a selected N,N-[(8 hydroxyquinoline)methyl]-substituted benzylamine (JLK1486) on melanoma cells and to characterize its mechanism of cell population growth inhibition. MATERIALS AND METHODS: In vitro cultures of B16F10 (mouse melanoma) cells were used as a model to characterize anti-proliferatory activity of JLK1486 using MTT growth assay, trypan blue viability assessment, cell cycle analysis, melanin production, beta galactosidase and acridine orange staining. RESULTS: Proliferating B16F10 and also MeWo (human melanoma) cells were strongly growth inhibited by JLK1486, displaying IC50 values of 196 nm and 110 nm respectively. Anti-proliferatory effects were independent of cell death and were characterized by a distinct accumulation of cells in G0 /G1 phase. Tyrosinase activity and relative melanin content remained unchanged indicating that the anti-proliferatory activity was not due to phenotype differentiation. Although treated B16F10 cells stained strongly positive for senescence marker beta-galactosidase, cells regained near normal proliferatory activity after removal of JLK1486. Increased acridine orange staining and presence of perinuclear vacuoles suggested induction of autophagy in B16F10 cells. Furthermore, JLK1486 pre-treatment completely abolished melphalan and antimycin A-induced apoptosis. CONCLUSION: JLK1486 provides a promising chemical scaffold to develop new anti-melanoma drugs or combination therapies, due to its potent inhibition of cell proliferation and induction of autophagy, at pharmacologically relevant concentrations. PMID- 25139617 TI - Effects of medical therapy or surgery on prostatic and bladder resistive indices in patients with benign prostatic hyperplasia. AB - INTRODUCTION: The effects of medical therapy or surgery on bladder and prostatic resistive indices (RIs) in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) were evaluated in the present study. PATIENTS AND METHODS: A total of 124 consecutive LUTS/BPH patients who were candidates for medical therapy (alfuzosin 10 mg once daily, n=66) or surgery (transurethral prostatectomy (TUR-P), n=58) were prospectively included. Baseline assessment of patients was performed with the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), and prostatic and bladder RIs measured using power Doppler imaging (PDI). All patients were re-evaluated 3 months after treatment measuring the same parameters. RESULTS: Following medical therapy, mean IPSS (17.2+/-5.1 vs. 8.3+/-5.3, p=0.0001), postvoiding residual (PVR) urine (80.0+/-80.5 vs. 40.3+/-38.6, p=0.0001), and prostatic RI (0.73+/-0.1 vs. 0.70+/-0.1, p=0.0001) were decreased, Qmax (13.7+/-4.2 vs. 16.9+/-5.9, p=0.0001) was increased, and bladder RI remained unchanged (0.70+/-0.1 vs. 0.70+/ 0.1, p=0.68). Mean IPSS (25.3+/-5.6 vs. 6.0+/-4.5, p=0.0001), PVR urine volume (134.5+/-115.5 vs. 35.7+/-25.9, p=0.0001), and prostatic (0.78+/-0.1 vs. 0.67+/ 0.04, p=0.0001) and bladder RIs (0.72+/-0.1 vs. 0.64+/-0.04, p=0.005) were decreased, and Qmax (8.0+/-4.5 vs. 17.2+/-8.2, p=0.0001) was increased after TUR P. CONCLUSIONS: Our results demonstrated that TUR-P decreased both prostatic and bladder RIs, while alpha-blocker therapy did not change bladder RI in the early posttreatment period in LUTS/BPH patients. PMID- 25139618 TI - Does pain interfere with antidepressant depression treatment response and remission in patients with depression and pain? An evidence-based structured review. AB - OBJECTIVE: The objective of this evidence-based structured review was to determine if there is consistent evidence that pain interferes with achieving antidepressant treatment response/remission of depression in patients with depression and pain. METHODS: After exclusion criteria were applied, of 2,801 studies/reports, 17 studies addressed this question. They were sorted into the four hypotheses outlined herein after. The percentage of studies supporting/not supporting each hypothesis was calculated. The strength and consistency of the evidence for each hypothesis were rated according to the Agency for Health Care Research and Quality (AHRQ) guidelines. RESULTS: For the first hypothesis (pretreatment pain levels will predict antidepressant depression response), nine out of 10 (90%) studies supported it. For the second hypothesis (treatment decreases in pain will be associated with antidepressant depression response), two out of two (100%) studies supported it. For the third hypothesis (pretreatment pain levels will predict antidepressant depression remission), six out of six (100%) studies supported it. For the fourth hypothesis (treatment decreases in pain will be associated with antidepressant depression remission), five out of five (100%) supported it. Utilizing these percentages and AHRQ guidelines, hypotheses 1, 3, and 4 received an A rating for consistency of studies in supporting them. A consistency rating for hypothesis 2 could not be generated because of too few studies in that group. CONCLUSIONS: Consistent evidence was found that antidepressant treatment of depression in patients with depression and pain can be negatively impacted by pain for achieving depression response/remission. However, the overall number of studies supporting each hypothesis was small. In addition, several potential confounders of the results of this study were identified. PMID- 25139620 TI - Downregulation of endogenous STAT3 augments tumoricidal activity of interleukin 15 activated dendritic cell against lymphoma and leukemia via TRAIL. AB - Effector functions in tumor resistance by dendritic cells (DCs) are less well characterized. In this study, we describe that the murine DCs upon stimulation with recombinant IL-15 in vitro or in vivo, expresses TNF superfamily member TRAIL which mediates cytotoxicity and growth inhibition against a murine lymphoma called Dalton lymphoma (DL) via apoptosis. Presence of tumor lysate or intact tumor cells significantly reduces the DC mediated tumoricidal effect, possibly via masking and down-regulating TRAIL in DCs. The antitumor effect of DC derived TRAIL was further augmented by deactivation of STAT3 in tumor cells by cucurbitacin I, which makes it more susceptible to DC derived TRAIL Treatment of tumor cells with cucurbitacin I upregulates TRAIL receptor expression in addition to activation of caspases. Compared to naive DCs, DCs from tumor bearing mice are significantly impaired in TRAIL expression and consequent antitumor functions against DL which was partially restored by activation with IL-15 or LPS. Priming with recombinant IL-15 prolongs the survival of tumor bearing mice treated with cucurbitacin I. Naive peripheral blood DCs derived from chronic myeloid leukemia (CML) patients have significant impairment in expression of TRAIL and consequent tumoricidal properties against TRAIL sensitive lymphoma cell lines and primary tumor cells compared to normal control. PMID- 25139619 TI - Celastrol induces unfolded protein response-dependent cell death in head and neck cancer. AB - The survival rate for patients with oral squamous cell carcinoma (OSCC) has not seen marked improvement in recent decades despite enhanced efforts in prevention and the introduction of novel therapies. We have reported that pharmacological exacerbation of the unfolded protein response (UPR) is an effective approach to killing OSCC cells. The UPR is executed via distinct signaling cascades whereby an initial attempt to restore folding homeostasis in the endoplasmic reticulum during stress is complemented by an apoptotic response if the defect cannot be resolved. To identify novel small molecules able to overwhelm the adaptive capacity of the UPR in OSCC cells, we engineered a complementary cell-based assay to screen a broad spectrum of chemical matter. Stably transfected CHO-K1 cells that individually report (luciferase) on the PERK/eIF2alpha/ATF4/CHOP (apoptotic) or the IRE1/XBP1 (adaptive) UPR pathways, were engineered [1]. The triterpenoids dihydrocelastrol and celastrol were identified as potent inducers of UPR signaling and cell death in a primary screen and confirmed in a panel of OSCC cells and other cancer cell lines. Biochemical and genetic assays using OSCC cells and modified murine embryonic fibroblasts demonstrated that intact PERK eIF2-ATF4-CHOP signaling is required for pro-apoptotic UPR and OSCC death following celastrol treatment. PMID- 25139621 TI - Erg cooperates with TGF-beta to control mesenchymal differentiation. AB - Transforming growth factor beta (TGF-beta) signaling plays an integral role in skeletal development. Conditional deletion of the TGF-beta type II receptor (Tgfbr2) from type II Collagen (Col2a) expressing cells results in defects in development of the annulus fibrosus (AF) of the intervertebral disc (IVD). We previously used microarray analysis to search for marker genes of AF as well as transcription factors regulated by TGF-beta during AF development. The transcription factor avian erythroblastosis virus E-26 (v-ets) oncogene related (Erg) was identified in the microarray screen as a candidate regulator of AF development. To study the effects of TGF-beta on AF differentiation and the role of Erg in this process, we used mouse sclerotome grown in micromass cultures. At 0.5ng TGF-beta/ml, sclerotome cells started to express markers of AF. Regulation of Erg by TGF-beta was confirmed in these cells. In addition, TGF-beta soaked Affi-gel beads implanted into the axial skeleton of stage HH 25 chick embryos showed that TGF-beta could induce expression of Erg mRNA in vivo. Next, an adenovirus to over-express Erg in primary sclerotome micromass cultures was generated. Over-expression of Erg led to a change in cell morphology and inhibition of differentiation into hyaline cartilage as seen by reduced Alcian blue staining and decreased Sox9 and c-Maf expression. Erg was not sufficient to induce expression of AF markers and expression of Sca1, a marker of pluripotent progenitor cells, was up-regulated in Erg expressing cells. When cells that ectopically expressed Erg were treated with TGF-beta, enhanced expression of specific differentiation markers was observed suggesting Erg can cooperate with TGF-beta to regulate differentiation of the sclerotome. Furthermore, we showed using co-immunopreciptiation that Erg and Smad3 bind to each other suggesting a mechanism for their functional interaction. PMID- 25139622 TI - An ADARPEF survey on respiratory management in pediatric anesthesia. AB - BACKGROUND: There have been recent changes with regard to tools and concepts for respiratory management of children undergoing general anesthesia. OBJECTIVES: To determine the practice of pediatric anesthetists concerning: preoxygenation, breathing systems, ventilation modes, anesthetic agent and airway device, strategies for a general anaesthetic of less than 30 min using spontaneous respiration, and opinion about technical aspects of ventilation. METHODS: Online questionnaire sent by e-mail to all the anesthetists registered on the mailing list of the French-speaking Pediatric Anesthetists and Intensivists Association (ADARPEF). RESULTS: 232 questionnaires (46%) were returned. More than 25% of anesthetists surveyed declared that they do not perform preoxygenation before induction for children <15 years old, apart from neonates and clinical specific situations. When performed, <65% chose a FiO2 higher than 80%. Inhalational induction with sevoflurane is the preferred mode of induction set at 6% or 8%, respectively, 69% [62-75] vs 25% [18-31]. For induction, the circle system was the most popular circuit used in all ages. The accessory breathing system Mapleson B type-was predominantly used for neonates (44% [37-54]). For maintenance of an anesthesia lasting <30 min in spontaneous breathing, the use of laryngeal mask increased with age, and the endotracheal tube was reserved for neonates (40% [33-48]). Pressure support ventilation was rarely used from the beginning of induction but was widely used for maintenance, whatever the age group. Results differed according to the type of institution. CONCLUSION: Ventilation management depends on the age and institutions in terms of circuit, airway device or ventilation mode, and specific differences exist for neonates. PMID- 25139624 TI - In vivo correlation between axon diameter and conduction velocity in the human brain. AB - The understanding of the relationship between structure and function has always characterized biology in general and neurobiology in particular. One such fundamental relationship is that between axon diameter and the axon's conduction velocity (ACV). Measurement of these neuronal properties, however, requires invasive procedures that preclude direct elucidation of this relationship in vivo. Here we demonstrate that diffusion-based MRI is sensitive to the fine microstructural elements of brain wiring and can be used to quantify axon diameter in vivo. Moreover, we demonstrate the in vivo correlation between the diameter of an axon and its conduction velocity in the human brain. Using AxCaliber, a novel magnetic resonance imaging technique that enables us to estimate in vivo axon diameter distribution (ADD) and by measuring the interhemispheric transfer time (IHTT) by electroencephalography, we found significant linear correlation, across a cohort of subjects, between brain microstructure morphology (ADD) and its physiology (ACV) in the tactile and visual sensory domains. The ability to make a quantitative assessment of a fundamental physiological property in the human brain from in vivo measurements of ADD may shed new light on neurological processes occurring in neuroplasticity as well as in neurological disorders and neurodegenerative diseases. PMID- 25139623 TI - Cerebellar control of gait and interlimb coordination. AB - Synaptic and intrinsic processing in Purkinje cells, interneurons and granule cells of the cerebellar cortex have been shown to underlie various relatively simple, single-joint, reflex types of motor learning, including eyeblink conditioning and adaptation of the vestibulo-ocular reflex. However, to what extent these processes contribute to more complex, multi-joint motor behaviors, such as locomotion performance and adaptation during obstacle crossing, is not well understood. Here, we investigated these functions using the Erasmus Ladder in cell-specific mouse mutant lines that suffer from impaired Purkinje cell output (Pcd), Purkinje cell potentiation (L7-Pp2b), molecular layer interneuron output (L7-Deltagamma2), and granule cell output (alpha6-Cacna1a). We found that locomotion performance was severely impaired with small steps and long step times in Pcd and L7-Pp2b mice, whereas it was mildly altered in L7-Deltagamma2 and not significantly affected in alpha6-Cacna1a mice. Locomotion adaptation triggered by pairing obstacle appearances with preceding tones at fixed time intervals was impaired in all four mouse lines, in that they all showed inaccurate and inconsistent adaptive walking patterns. Furthermore, all mutants exhibited altered front-hind and left-right interlimb coordination during both performance and adaptation, and inconsistent walking stepping patterns while crossing obstacles. Instead, motivation and avoidance behavior were not compromised in any of the mutants during the Erasmus Ladder task. Our findings indicate that cell type-specific abnormalities in cerebellar microcircuitry can translate into pronounced impairments in locomotion performance and adaptation as well as interlimb coordination, highlighting the general role of the cerebellar cortex in spatiotemporal control of complex multi-joint movements. PMID- 25139625 TI - Endogenous-cue prospective memory involving incremental updating of working memory: an fMRI study. AB - INTRODUCTION: Prospective memory paradigms are conventionally classified on the basis of event-, time-, or activity-based intention retrieval. In the vast majority of such paradigms, intention retrieval is provoked by some kind of external event. However, prospective memory retrieval cues that prompt intention retrieval in everyday life are commonly endogenous, i.e., linked to a specific imagined retrieval context. We describe herein a novel prospective memory paradigm wherein the endogenous cue is generated by incremental updating of working memory, and investigated the hemodynamic correlates of this task. METHODS: Eighteen healthy adult volunteers underwent functional magnetic resonance imaging while they performed a prospective memory task where the delayed intention was triggered by an endogenous cue generated by incremental updating of working memory. Working memory and ongoing task control conditions were also administered. RESULTS: The 'endogenous-cue prospective memory condition' with incremental working memory updating was associated with maximum activations in the right rostral prefrontal cortex, and additional activations in the brain regions that constitute the bilateral fronto-parietal network, central and dorsal salience networks as well as cerebellum. In the working memory control condition, maximal activations were noted in the left dorsal anterior insula. CONCLUSIONS: Activation of the bilateral dorsal anterior insula, a component of the central salience network, was found to be unique to this 'endogenous-cue prospective memory task' in comparison to previously reported exogenous- and endogenous-cue prospective memory tasks without incremental working memory updating. Thus, the findings of the present study highlight the important role played by the dorsal anterior insula in incremental working memory updating that is integral to our endogenous-cue prospective memory task. PMID- 25139626 TI - Erratum to: Glutamate receptors of the delta family are widely expressed in the adult brain. PMID- 25139627 TI - [Care of geriatric otorhinolaryngology patients]. PMID- 25139628 TI - Standard of care and future pharmacological treatment options for malignant glioma: an urgent need for screening and identification of novel tumor-specific antigens. AB - INTRODUCTION: Malignant gliomas (MGs) represent the most common primary brain tumors in adults, the most deadly of which is grade IV glioblastoma. Patients with glioblastoma undergoing current standard-of-care therapy have a median survival of 12 - 15 months. AREAS COVERED: Over the past 25 years, there have been modest advancements in the treatment of MGs. Assessment of therapeutic responses has continued to evolve to account for the increasing number of agents being tested in the clinic. Currently approved therapies for primary tumors have been extended for use in the setting of recurrent disease with modest efficacy. Agents initially approved for recurrent gliomas have begun to demonstrate efficacy against de novo tumors but will ultimately need to be evaluated in future studies for scheduling, timing and dosing relative to chemotherapy. EXPERT OPINION: Screening and identification of tumor-specific mutations is critical for the advancement of effective therapy that is both safe and precise for the patient. Two unique antigens found in glioblastoma are currently being employed as targets for immunotherapeutic vaccines, one of which has advanced to Phase III testing. Whole genome sequencing of MGs has yielded two other novel mutations that offer great promise for the development of molecular inhibitors. PMID- 25139629 TI - Mandarin version of the Leeds Dyspepsia Questionnaire: A valid instrument for assessing symptoms in Asians. AB - OBJECTIVE: To develop and validate a Mandarin version of the Leeds Dyspepsia Questionnaire (M-LDQ) in Asian patients with dyspepsia. METHODS: The M-LDQ was developed according to standardized methods. The validity, internal consistency, test-retest reliability and responsiveness of the instrument were evaluated in both primary and secondary care patients. RESULTS: A total of 184 patients (mean age 54.0 +/- 15.8 years, of whom 59% were women and 72.3% of whom had at least secondary level education) were recruited between August 2012 and March 2013, from both primary (n = 100) and secondary care clinics (n = 84). Both the internal consistency of all components of the M-LDQ (Cronbach's alpha 0.79) and test-retest reliability (Spearman's correlation coefficient 0.78) were good. The M-LDQ was valid in diagnosing dyspepsia in primary care (area under the receiver operating characteristics curve 0.84) and was able to discriminate between secondary and primary care patients (median cumulative LDQ score 13.0 vs 3.0, P < 0.0001). Among eight patients with organic dyspepsia, the median M-LDQ score reduced significantly from 21.0 (pretreatment) to 9.5 (4 weeks post-treatment) (P < 0.0001). CONCLUSION: The M-LDQ is a valid and responsive instrument for assessing ethnic Chinese adults with dyspepsia. PMID- 25139630 TI - Outcomes in acute heart failure: 30-day readmission versus death. AB - For patients hospitalized with acute heart failure, health policy initiatives in the USA have drawn attention to 30-day mortality and readmission. Confusion around definitions, populations, and thus reported rates for these two outcomes is common. Among Medicare fee-for-service patients hospitalized with heart failure, all-cause mortality 30 days from the time of admission is 11.7 % and all cause unplanned readmission 30 days from discharge is 23.0 %. Rates for Medicaid and commercially insured patients are lower. Mortality rates have been relatively stable, while readmission rates increased under the Diagnosis Related Group payment system then began decreasing under the Hospital Readmission Reductions Program. Risk models are reasonable at predicting mortality, whereas readmission has been harder to anticipate. The use of risk-standardized hospital rates as performance measures has generated considerable debate. Future work should clarify the interaction between the two measures, the optimal time window and factors influencing rates and trends-including socioeconomic status. PMID- 25139631 TI - Patterns and determinants of new first-line antihyperglycaemic drug use in patients with type 2 diabetes mellitus. AB - AIMS: We evaluated the patterns and determinants that influence the selection, timing and duration of first-line antihyperglycaemic drug (AHD) treatment in patients with type 2 diabetes in Germany, focusing specifically on treatment naive AHD initiators. METHODS: Pharmacy dispensing claims data were linked with a cohort of patients newly enrolled in a German Disease Management Program for type 2 diabetes (DMP-DM2) between 2003 and 2009. We examined uptake of first-line pharmacotherapy in previously unmedicated patients and identified predictors of receiving AHD therapy in general and metformin in particular using multivariable regression analyses. RESULTS: There were 27,138 unmedicated patients with type 2 diabetes and 47.0% of them were started on AHD treatment within 5 years after enrollment. Initial severity of diabetes was the major predictor of receiving first-line pharmacotherapy. Metformin accounted for 63% of newly prescribed AHD in 2003 and more than 80% in 2009 while sulfonylureas accounted for only 10%. Initiating metformin as first-line AHD was associated with younger age, higher BMI, lower HbA1c, and shorter diabetes duration (multivariate p<0.001 for all). Therapy switch or step-up was less frequent among metformin initiators than sulfonylurea initiators. CONCLUSIONS: The majority of patients were not started on AHD therapy within 5 years after enrollment. In line with recent therapy guidelines, current first-line antihyperglycaemic treatment was increasingly based on metformin. AHD initiators started on sulfonylurea were generally more advanced in their disease and were started later on primary pharmacotherapy. PMID- 25139632 TI - Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia. AB - AIMS: To identify risk factors and clinical biomarkers of prevalent diabetes foot complications, including foot ulcers, gangrene and amputations among patients with diabetes in Jeddah, Saudi Arabia. METHODS: 598 diabetes patients from Jeddah participated in the current study. Patients were considered to have diabetes foot complications if they reported diagnosis of foot ulcers or gangrene or amputations in a questionnaire administered by a physician and confirmed by clinical exams. Information on socio-demographic and lifestyle variables was self reported by patients, and several clinical markers were assessed following standard procedures. RESULTS: The prevalence of diabetes foot complications in this population was 11.4%. In the multivariable model without adjustment for PAD (peripheral artery disease) and DPN (diabetes peripheral neuropathy), non-Saudi nationality, longer diabetes duration and insulin use was significantly associated with higher diabetes foot complications prevalence. Each 1g/L increase of hemoglobin was associated with 2.8% lower prevalence of diabetes foot complications. In the multivariable model adjusting for PAD and DPN, the previously observed associations except for nationality were no longer significant. Patients with both DPN and PAD had 9.73 times the odds of diabetes foot complications compared to the patients with neither condition. CONCLUSION: In this population, longer diabetes duration, insulin use, lower hemoglobin levels and non-Saudi nationality were associated with higher prevalence of foot complications. These associations were largely explained by the presence of DPN and PAD except for non-Saudi nationality. Diabetes patients with both DPN and PAD had nearly 10-fold increased risk of foot complications than those with neither condition. PMID- 25139633 TI - Pulmonary vascular tone is dependent on the central modulation of sympathetic nerve activity following chronic intermittent hypoxia. AB - Chronic intermittent hypoxia (IH) provokes a centrally mediated increase in sympathetic nerve activity (SNA). Although this sympathetic hyperexcitation has been linked to systemic hypertension, its effect on the pulmonary vasculature is unclear. This study aimed to assess IH-mediated sympathetic excitation in modulating pulmonary vasculature tone, particularly acute hypoxia vasoconstrictor response (HPV), and the central beta-adrenergic signaling pathway for facilitating the increase in SNA. Sprague-Dawley rats were exposed to IH (cycle of 4% O2 for 90 s/air for 90 s) for 8 h/day for 6 weeks. Subsequently, rats were anesthetized and either pulmonary SNA was recorded (electrophysiology), or the pulmonary vasculature was visualized using microangiography. Pulmonary sympathetic and vascular responses to acute hypoxia were assessed before and after central beta1-adrenergic receptor blockade (Metoprolol, 200 nmol i.c.v.). Chronic IH increased baseline SNA (110% increase), and exacerbated the sympathetic response to acute hypoxia. Moreover, the magnitude of HPV in IH rats was blunted compared to control rats (e.g., 10 and 20% vasoconstriction, respectively). In only the IH rats, beta1-receptor blockade with metoprolol attenuated the hypoxia-induced increase in pSNA and exacerbated the magnitude of acute HPV, so that both sympathetic and HPV responses were similar to that of control rats. Interestingly, the expression of beta1-receptors within the brainstem was similar between both control and IH rats. These results suggest that the centrally mediated increase in SNA following IH acts to blunt the local vasoconstrictor effect of acute hypoxia, which reflects an inherent difference between vasodilator and vasoconstrictor actions of SNA in pulmonary and systemic circulations. PMID- 25139634 TI - Metabolomic analysis of amino acid and fat metabolism in rats with L-tryptophan supplementation. AB - Tryptophan (TRP) is an important precursor for several neurotransmitters and metabolic regulators, which play a vital role in regulating nutrient metabolism. The purpose of this study was to investigate the effects of tryptophan supplementation on the biochemical profiles, intestinal structure, liver structure and serum metabolome in rats. Rats received daily intragastric administration of either tryptophan at doses of 200 mg/kg body weight per day or saline (control group) for 7 days. TRP supplementation had a tendency to decrease the body weight of rats (P > 0.05). The levels of urea and CHO in serum were decreased in the TRP-supplemented group rats compared with control group rats (P < 0.05). TRP supplementation increased the villus height and the ratio of villus height to crypt depth in the jejunum compared to control group rats (P < 0.05). Metabolic effects of tryptophan supplementation include: (1) increases in the serum concentrations of lysine, glycine, alanine, glutamate, glutamine, citrulline, methionine, tyrosine, 1-methylhistidine, and albumin, and decreases in the concentrations of serum branched-chain amino acid (isoleucine, valine and leucine); (2) decreases in the serum concentrations of formate and nitrogenous products (trimethylamine, TMAO, methylamine and dimethylamine), and in the contraction of trimethylamine in feces; (3) decreases in serum levels of lipids, low density lipoprotein, very low density lipoprotein, together with the elevated ratio of acetoacetate to beta-hydroxybutyrate. The results indicate that tryptophan supplementation reduced the catabolism of dietary amino acids and promoted protein synthesis in rats, promoted the oxidation of fatty acid and reduced fat deposition in the body of rats. PMID- 25139635 TI - A review of the economic tools for assessing new medical devices. AB - Whereas the economic evaluation of pharmaceuticals is an established practice within international health technology assessment (HTA) and is often produced with the support of comprehensive methodological guidance, the equivalent procedure for medical devices is less developed. Medical devices, including diagnostic products, are a rapidly growing market in healthcare, with over 10,000 medical technology patent applications filed in Europe in 2012-nearly double the number filed for pharmaceuticals. This increase in the market place, in combination with the limited, or constricting, budgets that healthcare decision makers face, has led to a greater level of examination with respect to the economic evaluation of medical devices. However, methodological questions that arise due to the unique characteristics of medical devices have yet to be addressed fully. This review of journal publications and HTA guidance identified these characteristics and the challenges they may subsequently pose from an economic evaluation perspective. These unique features of devices can be grouped into four categories: (1) data quality issues; (2) learning curve; (3) measuring long-term outcomes from diagnostic devices; and (4) wider impact from organisational change. We review the current evaluation toolbox available to researchers and explore potential future approaches to improve the economic evaluation of medical devices. PMID- 25139636 TI - Autoimmune pulmonary alveolar proteinosis co-existing with breast cancer: a case report. AB - INTRODUCTION: Pulmonary alveolar proteinosis is a rare pulmonary disease characterized by excessive alveolar accumulation of surfactant due to defective alveolar clearance by macrophages. There are only a few published case reports of pulmonary alveolar proteinosis occurring in association with solid cancers. To the best of our knowledge, there are no previously reported cases of pulmonary alveolar proteinosis associated with breast cancer. CASE PRESENTATION: A 48-year old Asian woman, a nonsmoker, presented to our institution with a right breast mass. Biopsy examination of the lesion revealed scirrhous carcinoma. A chest computed tomography scan for metastases showed abnormal shadows in both upper lung fields. As a result of flexible fiberscopic bronchoscopy, this patient was diagnosed as having pulmonary alveolar proteinosis. This case was categorized as autoimmune pulmonary alveolar proteinosis due to the positive anti-granulocyte macrophage colony-stimulating factor antibody. Pulmonary alveolar proteinosis decreased gradually after mastectomy. CONCLUSIONS: The present case involved the coincident occurrence of autoimmune pulmonary alveolar proteinosis with breast cancer; breast cancer may be a factor during pulmonary alveolar proteinosis development. PMID- 25139638 TI - Role of dietary fats in the prevention and treatment of the metabolic syndrome. AB - A symposium on the health significance of dietary fat in the prevention and treatment of the metabolic syndrome (MetS) was held at the 20th International Congress of Nutrition in Granada, Spain, on September 19, 2013. Four nutrition experts addressed the topics of dietary fat and obesity, effects of dietary fat quality in obesity and insulin resistance, influence of early nutrition on the later risk of MetS and the relative merits of high- or low-fat diets in counteracting MetS. Participants agreed that preventing weight gain and achieving weight loss in overweight and obese patients were key strategies for reducing MetS. Both low-fat and low-carbohydrate diets are associated with weight loss, but adherence to the diet is the most important factor in achieving success. Avoidance of high saturated fats contributes to lower health risks among obese, MetS and diabetic patients. Further, healthy maternal weight at conception and in pregnancy is more important that weight gain during pregnancy for reducing the risk of obesity in the offspring. The effects of different polyunsaturated fatty acids on MetS and weight loss require clarification. PMID- 25139639 TI - TACE performed in patients with a single nodule of hepatocellular carcinoma. AB - BACKGROUND: Patients with single hepatocellular carcinoma (HCC) usually undergo transarterial chemoembolization (TACE) if they are not candidates for curative surgical or ablative therapy. The primary aim of the study was to assess the overall survival and clinical determinants of survival in patients with single HCC who underwent TACE. The secondary aims were tumor response, local and distant recurrence rates, time to recurrence and the impact of TACE on liver function. METHODS: The outcomes of 148 consecutive patients with single HCC who underwent TACE from January 2004 to December 2009 were retrospectively analyzed. RESULTS: Complete response (CR) was observed in 95/148 (64%) patients and a partial response (PR) in 39 (26%) patients. The recurrence rate was 27%, 42% and 65% at 6, 12 and 24 months, respectively. The day after TACE, 56 (38%) patients had a Child-Pugh increase >= 1 and 93 (63%) had a MELD increase >= 1. Median survival was 36.0 months with 1-, 3- and 5-year survival rates of 85%, 50% and 26%, respectively. Bland portal thrombosis was not seen to have any impact at univariate survival analysis; however, a slight impairment of PS (PS-1) in small tumors had some, although minor, impact on prognosis. Factors associated with shorter survival at multivariate analysis were tumor >5 cm, absence of CR, ascites, alpha-fetoprotein (AFP) >= 14.5 ng/mL and a MELD increase >= 1. CONCLUSIONS: Transarterial chemoembolization is a valid treatment option in patients with single HCC not suitable for curative treatment. Bland PVT has no major impact on survival and a slight impairment of PS attributable to cirrhosis in patients within the Milan criteria should not preclude the use of TACE. PMID- 25139640 TI - First you find the "criminals" in research fraud. PMID- 25139641 TI - Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal cell carcinoma: qualitative and quantitative CEUS characteristics and distinguishing features. AB - PURPOSE: To determine the contrast-enhanced ultrasonography (CEUS) characteristics of minimal fat renal angiomyolipoma (AML) (triphasic and epithelioid) and compare them to each other and to clear cell renal cell carcinoma (ccRCC) to explore their differential diagnostic clue. METHODS: Qualitative and quantitative CEUS analyses were retrospectively conducted for epithelioid renal AMLs (EAMLs) (n = 15), triphasic minimal fat AMLs (TAMLs) (n = 25), and ccRCCs (n = 113). Enhancement patterns and features with CEUS were qualitatively evaluated. As for the quantitative parameters, rise times (RT), time to peak (TTP), and tumor-to-cortex enhancement ratio (TOC ratio) were compared among these renal tumor histotypes. RESULTS: No significant differences were detected on conventional ultrasound in the three histotypes of renal tumor. On qualitative CEUS analysis, centripetal enhancement in cortical phase (73.3% in EAMLs, 84.0% in TAMLs vs. 18.6% in ccRCCs, p < 0.001 for both), homogeneous peak enhancement (100.0% in both EAMLs and TAMLs vs. 43.4% in ccRCCs, p < 0.001 for both), and iso-enhancement in parenchyma phase (53.3% in AMLs, 52.0% in TAMLs vs. 26.5% in ccRCCs, p = 0.034 and 0.013, respectively) were valuable traits for differentiating EAMLs and TAMLs from ccRCCs. Furthermore, with quantitative analysis, RT and TTP were much shorter in ccRCCs than those in EAMLs and TAMLs. However, all these qualitative and quantitative characteristics made no significant difference between EAMLs and TAMLs. In the differential diagnosis of EAMLs from TAMLs, pseudocapsule sign was valuable (40.0% in EAMLs vs. 0.0% in TAMLs, p < 0.001), and TOC ratio was much higher in EAMLs (166.01 +/- 64.47%) than that in TAMLs (93.74 +/- 46.56%)(p < 0.001), though they did make overlaps with ccRCCs. With either heterogeneous peak enhancement or the presence of pseudocapsule or TOC ratio >97.34% as the criteria to differentiate ccRCCs and EAMLs from TAMLs, the sensitivity and specificity were 80.0% and 87.5%, respectively. CONCLUSIONS: Qualitative and quantitative CEUS analyses are helpful in the differential diagnosis of ccRCCs, EAMLs, and TAMLs. PMID- 25139642 TI - The role of pure iterative reconstruction in conventional dose CT enterography. AB - PURPOSE: Pure iterative reconstruction (Pure IR) has been proposed as a solution to improve diagnostic quality of low dose CT images. We assess the performance of model based iterative reconstruction (MBIR) in improving conventional dose CT enterography (CTE) images. METHODS: 43 Crohn's patients (27 female) (38.5 +/- 12.98 years) referred for CTE were included. Images were reconstructed with pure IR (MBIR, General Electric Healthcare) in addition to standard department protocol (reconstructed with hybrid iterative reconstruction (Hybrid IR) [60% filtered back projection/40% adaptive statistical IR (General Electric Healthcare)]. Image quality was assessed objectively and subjectively at 6 anatomical levels. Clinical interpretation was undertaken in consensus by 2 blinded radiologists along with 2 non-blinded readers ('gold standard'). Results were analyzed using Statistical Package for Social Scientists. RESULTS: Mean effective radiation dose was 6.05 +/- 2.84 mSv (size specific dose estimates 9.25 +/- 2.9 mGy). Objective and subjective assessment yielded 6106 data points. Pure IR images significantly outperformed those using standard reconstruction techniques across all subjective (p < 0.001 for all comparisons) (noise, contrast resolution, spatial resolution, streak artifact, axial diagnostic acceptability, coronal diagnostic acceptability) and objective (p < 0.004) (noise, signal-to noise ratio) parameters. Clinical reads of the pure IR images agreed more closely with the gold standard reads than the hybrid IR image reads in terms of overall Crohn's activity grade (kappa = 0.630, 0.308) and detection of acute complications (kappa = 1.0, 0.896). Results were comparable for bowel wall disease severity assessment (kappa = 0.523, 0.593). CONCLUSIONS: Pure IR considerably improves image quality of conventional dose CTE images and therefore its use should be expanded beyond low dose protocols to improving image quality at conventional dose CT imaging. PMID- 25139643 TI - Multimodality imaging of common and uncommon peritoneal diseases: a review for radiologists. AB - Peritoneal disease can be caused by a wide spectrum of pathologies. While peritoneal disease is usually caused by primary or secondary malignancies, benign diseases can occur and mimic malignancies. This article begins with an overview of peritoneal embryology and anatomy followed by a detailed description of the multimodality imaging appearance of peritoneal diseases. Common diseases include peritoneal carcinomatosis, pseudomyxoma peritonei, lymphomatosis, sarcomatosis, and tuberculous peritonitis. The uncommon diseases which cause peritoneal disease include desmoid fibromatosis, desmoplastic small round cell tumor, malignant mesothelioma, well-differentiated mesothelioma, multicystic mesothelioma, papillary serous carcinoma, leiomyomatosis, extramedullary hematopoiesis, inflammatory pseudotumor and amyloidosis. This manuscript will help the radiologist become familiar with the different peritoneal spaces, pathways of spread, multimodality imaging appearance and differential diagnoses of peritoneal diseases in order to report the essential information for surgeons and oncologists to plan treatment. PMID- 25139644 TI - Far-field atrial sensing by the left ventricular channel of a biventricular device. AB - BACKGROUND: The left ventricular (LV) channel of Biotronik biventricular devices used for cardiac resynchronization therapy (CRT) is designed with the capability of sensing via the LV lead. Therefore a displaced LV lead in a coronary vein could sense far-field atrial signals and interfere with CRT. METHODS: The Biotronik troubleshooting archives containing data of approximately 700 transvenous CRT-D cases (D = defibrillator) were examined for atrial far-field sensing by the LV channel. We selected three cases from the archives to demonstrate the typical features of LV sensing of far-field atrial activity. RESULTS: We found 3 typical cases of far-field atrial sensing by the LV channel. The LV lead was displaced in 2 cases and possibly in the third patient. Two cases exhibited short intervals between LV sensed events (LVs-LVs = 207-218 ms), a finding typical of this form of far-field atrial sensing by an LV lead. In the third case, short LVs-LVs intervals were not observed because spontaneous LV activation failed to generate an LVs marker (corresponding with the terminal LVs marker in a short LVs-LVs interval). LV activity was unsensed during the blanking period of the LV upper rate interval initiated by the first LVs that actually generated by far-field oversensing. This response was also observed intermittently in a patient who presented with short LVs-LVs intervals. CONCLUSIONS: Far-field atrial oversensing by the LV channel of a CRT-D device occurs mostly with LV lead displacement. The diagnosis is important because it interferes with the delivery of therapeutic CRT but it is not life-threatening. Oversensing can be easily corrected by simple reprogramming of the device or LV lead repositioning if there is high LV pacing threshold. PMID- 25139645 TI - Synthesis and properties of single domain sphere-shaped barium hexa-ferrite nano powders via an ultrasonic-assisted co-precipitation route. AB - To synthesize high quality barium hexa-ferrite nano powders, an ultrasonic assisted co-precipitation method has been used and the influences of the ultrasonic technique on the particle morphologies and magnetic properties of the synthesized barium hexa-ferrite nano powders have been investigated. The results indicated that the introduction of ultrasonic energy into the co-precipitation process promoted the composition homogeneities of the co-precipitated precursors, minished their particle sizes, and exerted the additional surface barriers between the particles, which influenced both the phase formation and particle growth-up processes during the subsequent heating treatment and altered the particle sizes, size distributions and particle shapes of the final synthesized powders. The average particle sizes of the synthesized nano powders dramatically decreased from 210 nm to about 100 nm as the inputting ultrasonic power increased, while the size distribution became increasingly uniform except for a few of large particles existed as the inputting power approached to a high value. The magnetization at 1.4 T of the as-synthesized barium hexa-ferrite dramatically increased and approached to the highest value of 57.9 emu/g due to the elimination of multi-domain particles, the alleviation of particle adhesion and the evolution of particle shape from flake to quasi-sphere as well as the uniform particle size distribution as the ultrasonic assistance was employed, and slightly decreased because of the coarsening in particle sizes. PMID- 25139646 TI - Stable carbon isotope ratio profiling of illicit testosterone preparations- domestic and international seizures. AB - Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) is now established as a robust and mature analytical technique for the doping control of endogenous anabolic androgenic steroids in human sport. It relies on the assumption that the carbon isotope ratios of naturally produced steroids are significantly different to synthetically manufactured testosterone or testosterone prohormones used in commercial medical or dietary supplement products. Recent publications in this journal have highlighted the existence of black market testosterone preparations with carbon isotope ratios within the range reported for endogenous steroids (i.e. delta(13) C >= -25.8 0/00). In this study, we set out to profile domestic and international law enforcement seizures of illicit testosterone products to monitor the prevalence of 'enriched' substrates--which if administered to human subjects would be considered problematic for the use of current GC-C-IRMS methodologies for the doping control of testosterone in sport. The distribution of delta(13) C values for this illicit testosterone sample population (n = 283) ranged from -23.4 0/00 to -32.9 0/00 with mean and median of -28.6 0/00--comparable to previous work. However, only 13 out of 283 testosterone samples (4.6 %) were found to display delta(13) C values >= -25.8 0/00, confirming that in the vast majority of cases of illicit testosterone administration, current GC-C-IRMS doping control procedures would be capable of confirming misuse. PMID- 25139647 TI - Electroconvulsive stimulation, but not chronic restraint stress, causes structural alterations in adult rat hippocampus--a stereological study. AB - The neurobiological mechanisms underlying depression are not fully understood. Only a few previous studies have used validated stereological methods to test how stress and animal paradigms of depression affect adult hippocampal neurogenesis and whether antidepressant therapy can counteract possible changes in an animal model. Thus, in this study we applied methods that are state of the art in regard to stereological cell counting methods. Using a validated rat model of depression in combination with a clinically relevant schedule of electroconvulsive stimulation, we estimated the total number of newly formed neurons in the hippocampal subgranular zone. Also estimated were the total number of neurons and the volume of the granule cell layer in adult rats subjected to chronic restraint stress and electroconvulsive stimulation either alone or in combination. We found that chronic restraint stress induces depression-like behavior, without significantly changing neurogenesis, the total number of neurons or the volume of the hippocampus. Further, electroconvulsive stimulation prevents stress-induced depression-like behavior and increases neurogenesis. The total number of neurons and the granule cell layer volume was not affected by electroconvulsive stimulation. PMID- 25139648 TI - [The future of the CT scan; will CT replace conventional radiography?]. AB - The number of CT scans being made has increased over the past few years. New CT technology has been developed to reduce the individual patient radiation dose. By using this technology it is possible to make CT scans with a radiation dose approaching conventional X-rays, which means that in the future radiation dose may not form a limitation to making CT scans. The indication for CT scans will broaden, and low-dose CT scans will increasingly replace conventional radiography. PMID- 25139649 TI - [Delusional infestation, a therapeutic challenge]. AB - Delusional infestation, formally known as delusional parasitosis, poses a therapeutic challenge. This article provides tools to engage these patients with psychiatric treatment. We present two men aged 49 and 48 who saw the dermatologist with skin symptoms due to primary and secondary delusional infestation, respectively. Despite their anosognosia, both patients were successfully treated with antipsychotics thanks to the collaboration between dermatology and psychiatry. To increase the acceptability of treatment with antipsychotics, emphasis should be placed on their antipruritic properties and the effect on degree of preoccupation with the infection rather than their antipsychotic properties. Follow-up is important, as patients mostly do not attribute their recovery to antipsychotics and the risk of recurrence is high after cessation of antipsychotic medication. PMID- 25139650 TI - [Risks of intrahepatic cholestasis of pregnancy]. AB - Intrahepatic cholestasis of pregnancy (ICP) is defined as pruritus during pregnancy in the absence of primary skin lesions, combined with an increase in serum total bile salts and/or abnormal serum liver tests. This article provides an insight into the diagnostic and therapeutic considerations by presenting two cases. ICP usually presents around 34 weeks of gestation, but can be present early in pregnancy as described in a 32-year-old patient pregnant after in-vitro fertilization. DNA analysis showed a mutation in the ABCB4 gene, causing MDR3 deficiency. Ursodeoxycholic acid treatment seems to alleviate maternal pruritus and possibly reduces perinatal risks related to the severe form of ICP, defined as fasted serum bile salt levels of >= 40 MUmol/l at any point during the pregnancy. Short-term rifampicin treatment can be considered in patients with persistent pruritus. Induction of labour is advised only after 37 weeks of gestation in patients with severe ICP. PMID- 25139651 TI - [Ethnic differences in uptake of professional maternity care assistance]. AB - OBJECTIVE: To examine the ethnic differences in the uptake of professional maternity care assistance (MCA) in the Netherlands, and the factors that may explain these differences. Additionally the effect of MCA on health risk behaviour around infants is examined. DESIGN: Questionnaire survey. METHOD: Questionnaire data from 3967 mothers from the ABCD study (Amsterdam Born Children and their Development) included during pregnancy in 2003-2004, were used. We examined the explanatory role of ethnicity, age, socioeconomic status, mastery of the Dutch language, parity, housing situation and place of giving birth on MCA uptake, and the effect of MCA uptake on health risk behaviour around infants, such as smoking indoors, infant sleep behaviour, infant nutrition, and response to infant crying. RESULTS: Mothers of non-Western origin less often used MCA than Dutch mothers (Ghanaian: 70%; Turkish: 75%; Moroccan: 79%; Surinamese: 81%; Dutch Caribbean: 85% vs. Dutch: 95%). Higher educational level, better mastery of the Dutch language, having a paid job and home delivery were all independently associated with the uptake of MCA, and also partially explained ethnic differences in the uptake of MCA. Mothers who received MCA more often breastfed, more often gave vitamin K when not breastfeeding, and more often lived in smoke free homes. The protective effect of MCA was stronger for non-Western mothers than for Dutch mothers. CONCLUSION: Mothers of non-Western origin make less use of professional MCA. Given that the use of MCA is associated with a less risk behaviour around infants, efforts should be made to improve the accessibility of professional MCA for mothers of non-Western origin. PMID- 25139652 TI - [Interaction between NSAIDs and acetylsalicylic acid disregarded]. AB - In 2013 the European Medicines Agency declared that diclofenac is contraindicated in patients with arterial thrombotic complications, based on a meta-analysis of randomised controlled trials on the adverse reactions of NSAIDs. The same decision was taken for coxibs some years earlier. The Dutch authorities (CBG/MEB) informed physicians and pharmacists about this decision without taking into account whether these patients were using prophylactic acetylsalicylic acid or not. It has been shown that NSAIDs with high COX-1 affinity like ibuprofen and naproxen cause a pharmacodynamic interaction with the inhibition of thromboxane synthesis by acetylsalicylic acid. This interaction does not occur with relatively COX-2-selective NSAIDs such as coxibs and diclofenac. Therefore, in patients who use acetylsalicylic acid for thromboprophylaxis, contraindicating coxibs or diclofenac is not justified, on the contrary: they are preferable. PMID- 25139653 TI - [Potential lowering of sepsis-related mortality via screening and implementation of guidelines]. AB - The incidence of sepsis continues to increase. However, over the past decade marked reductions in sepsis-related in-hospital mortality have been reported. Large variations in the presentation and severity of illness may be encountered in ICU patients with severe sepsis, which might preclude the success of screening and guideline programmes. However, the authors of this article were able to prove that a national programme involving screening and a package of interventions did lower relative in-hospital mortality by 16.7% over 3.5 years in 52 participating hospitals in the Netherlands. In-hospital mortality did not change in 30 non participating hospitals. Therefore, the authors recommend implementing updated guidelines, sepsis quality indicators and programmes with a package of interventions to further reduce sepsis mortality. Furthermore, additional research on long term consequences in sepsis survivors is warranted. PMID- 25139654 TI - Fetal growth restriction as a perinatal and long-term health problem: clinical challenges and opportunities for future (4P) fetal medicine. PMID- 25139655 TI - Nanofiber scaffolds for treatment of spinal cord injury. AB - Spinal cord injury (SCI) is a common neurologic disorder that results in loss of sensory function and mobility. It is well documented that tissue engineering is a potential therapeutic strategy for treatment of SCI. In this connection, various biomaterials have been explored to meet the needs of SCI tissue engineering and these include natural materials, synthetic biodegradable polymers and synthetic non- degradable polymers. Nanofiber scaffolds are newly emerging biomaterials that have been widely utilized in tissue engineering recently. In comparison to the traditional biomaterials, nanofibers have advantages in topography and porosity, thus mimicking the naturally occurring extracellular matrix. Besides, they exhibit excellent biocompatibility with low immunogenicity, and furthermore they are endowed with properties that help to bridge the lesion cavity or gap, and serve as an effective delivery system for graft cells or therapeutic drugs. This review summarizes some of the unique properties of nanofiber scaffolds which are critical to their potential application in treatment of injured spinal cord. PMID- 25139656 TI - Hereditary cancer syndromes with high risk of endometrial and ovarian cancer: surgical options for personalized care. AB - Cancer genomics has increased our recognition of specific hereditary cancer mutations. Hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome are two such entities in which women carrying specific mutations may be at high risk for developing breast, ovarian, and/or endometrial cancers. Risk reducing surgery such as prophylactic mastectomy, oophorectomy, and/or hysterectomy may allow women to decrease these risks after completing childbearing. Background, indications, and consequences of these procedures are reviewed. PMID- 25139657 TI - Characterization of a mutant glucose isomerase from Thermoanaerobacterium saccharolyticum. AB - A series of site-directed mutant glucose isomerase at tryptophan 139 from Thermoanaerobacterium saccharolyticum strain B6A were purified to gel electrophoretic homogeneity, and the biochemical properties were determined. W139F mutation is the most efficient mutant derivative with a tenfold increase in its catalytic efficiency toward glucose compared with the native GI. With a maximal activity at 80 degrees C of 59.58 U/mg on glucose, this mutant derivative is the most active type ever reported. The enzyme activity was maximal at 90 degrees C and like other glucose isomerase, this mutant enzyme required Co(2+) or Mg(2+) for enzyme activity and thermal stability (stable for 20 h at 80 degrees C in the absence of substrate). Its optimum pH was around 7.0, and it had 86 % of its maximum activity at pH 6.0 incubated for 12 h at 60 degrees C. This enzyme was determined as thermostable and weak-acid stable. These findings indicated that the mutant GI W139F from T. saccharolyticum strain B6A is appropriate for use as a potential candidate for high-fructose corn syrup producing enzyme. PMID- 25139658 TI - Inactivation of Aleutian mink disease virus through high temperature exposure in vitro and under field-based composting conditions. AB - Disposal of manure contaminated with Aleutian mink disease virus (AMDV) is a significant concern to the mink industry. Inactivation of AMDV under field conditions has received limited attention in the scientific literature. We evaluated the thermal inactivation of AMDV in vitro and during composting of mink manure. Spleen homogenate containing AMDV was heated under controlled conditions at 45 degrees C, 55 degrees C, and 65 degrees C for 3 days. Results of the in vitro study identified complete absence of viral replication in mink at 65 degrees C only. Next, manure-mixed AMDV packed in polyester pouches was inserted in different layers of three replicate mink manure compost piles. The virus was retrieved after the compost piles had undergone a heating period and subsequently returned to ambient temperatures. Temperature regimes in the compost piles were categorized as >=65 degrees C, >=60-64 degrees C, and >=55-59 degrees C. Initially, layer-wise composite virus samples were assayed for virus replication in mink. Twenty-one-day post-inoculation (p.i.) plasma tested for AMDV and antibodies indicated infection in 40%, 80%, and 100% of mink inoculated from samples originating from the top, center and bottom layers of the piles, respectively. Subsequently, the virus was extracted from individual pouches in compost layers achieving thermal activity >=65 degrees C and was tested in mink. No antibodies or virus was detected in plasma taken weekly up to day 21 p.i. PCR data of bone marrow and lymph nodes collected on day 21 p.i. also showed no AMDV. However, mink that received virus from positive control manure indicated infection in their plasma as early as 1 week p.i. PMID- 25139659 TI - Evaluating the potential of marine Bacteriovorax sp. DA5 as a biocontrol agent against vibriosis in Litopenaeus vannamei larvae. AB - The potential application of Bdellovibrio-and-like organisms (BALOs) for the biocontrol of bacterial diseases has been widely recognized. However, no marine BALOs have been reported for Vibrio-related infections in penaeid shrimp. In the present study, the bacteriolytic ability of the marine Bacteriovorax strain DA5 against Vibrio alginolyticus zouA was examined by cocultivation and electron microscopy, and optimal lysis was observed at 30-35 degrees C and 20-300/00 salinity along with a high multiplicity of infection. Then, we showed that experimentally infected Litopenaeus vannamei larvae exhibited significantly higher survival with incremental DA5 levels. Finally, variation in the bacterial counts and the bacterial community in larval rearing water was investigated after prophylactic application of DA5. The elimination effect of DA5 on vibrios was visible at early time points, whereas only a few non-dominant bacteria, rather than the predominant populations, were affected through analysis of denaturing gradient gel electrophoresis of the 16S rDNA V3 region. Accordingly, the prophylactic and therapeutic efficacies of DA5 on vibriosis associated with L. vannamei could markedly enhance larval survivability, and these results will facilitate the application of marine Bacteriovorax to control vibriosis in shrimp larviculture. PMID- 25139660 TI - Recent developments in the effects of nitric oxide-donating statins on cardiovascular disease through regulation of tetrahydrobiopterin and nitric oxide. AB - Since the discovery of the importance of nitric oxide (NO) to the human body three decades ago, numerous laboratory and clinical studies have been done to explore its potential therapeutic actions on many organs. In the cardiovascular system, NO works as a volatile signaling molecule regulating the vascular permeability and vascular tone, preventing thrombosis and inflammation, as well as inhibiting the smooth muscle hyperplasia. Thus, NO is important in the prevention and treatment of cardiovascular disease. NO is synthesized by NO synthase (NOS) with tetrahydrobiopterin (BH4) as the crucial cofactor. Many studies have been done to form nitric oxide donors so as to deliver NO directly to the vessel walls. In addition, NO moieties have been incorporated into existing therapeutic agents to enhance the NO bioavailability, including statins. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA), the rate limiting enzyme of the mevalonate pathway. By inhibiting this pathway, statins lower blood cholesterol and exert their pleiotropic effects through activity in reaction cascades, such as Rho/ROCK and Rac 1/NADPH oxidase pathways. Statins have also been observed to implement their non-lipid effects by promoting BH4 synthesis with increase of NO bioavailability. Furthermore, NO-donating statins in laboratory studies have demonstrated to produce better therapeutic effects than their parent's drugs. They offer better anti-inflammatory, anti proliferative and antithrombotic actions on cardiovascular system. They also cause better revascularization in peripheral ischemia and produce greater enhancement in limb reperfusion and salvage. In addition, it has been shown that NO-donating statin caused less myotoxicity, the most common side effect related to treatment with statins. The initial studies have demonstrated the superior therapeutic effects of NO-donating statins while producing fewer side effects. PMID- 25139661 TI - Laparoscopic sleeve gastrectomy as a weight reduction strategy in obese patients after kidney transplantation. AB - Morbid obesity is associated with increased graft loss and shortened graft survival in kidney transplant patients. Treating obesity in transplant patients may improve graft outcomes. Laparoscopic sleeve gastrectomy (LSG), an effective bariatric operation, is relatively unlikely to interfere with absorption of anti rejection medications. Data on relevant renal function parameters were collected from all LSGs performed on renal transplant patients at our center (n = 10). The procedure was successful in eight patients, with no mortality, graft rejection or dysfunction. The median age and follow-up were 57 years and 14 months, respectively. Seven patients had over 1 year of follow-up. The median preoperative weight and BMI were 119 kg (96-152) and 42 kg/m(2) (37-49), respectively. The median hospital stay was 4 days. The median postoperative weight and BMI at 6 months and 1 year were 86 kg and 31 kg/m(2) and 83 kg and 29 kg/m(2) , respectively. Urinary protein excretion and serum creatinine decreased significantly in all patients (p < 0.05). One patient developed two complications, acute renal failure and sleeve stricture, both of which resolved with treatment. LSG provided effective weight loss in renal transplant patients without adverse effects on graft function and immunosuppression. PMID- 25139662 TI - Progressive rash and fever in an infant. PMID- 25139663 TI - Would the Use of Bedside Bladder Ultrasound Decrease the Necessity of Invasive Bladder Catheterization in the Pediatric Intensive Care Unit? PMID- 25139664 TI - Breastfeeding in African Americans may not depend on sleep arrangement: a mixed methods study. AB - BACKGROUND: Despite high bedsharing rates, breastfeeding rates are low among African Americans. OBJECTIVE: Describe the association between breastfeeding and bedsharing; elucidate barriers to breastfeeding in African Americans. METHODS: African American mothers with infants <6 months were recruited for this cross sectional, mixed-methods study and completed an infant care practices survey. A subgroup participated in focus groups or individual interviews. RESULTS: A total of 412 completed the survey; 83 participated in a focus group or interview. Lower socioeconomic status mothers were more likely to breastfeed exclusively or at all if they bedshared (P = .02 and P = .01, respectively). Bedsharing was not associated with breastfeeding among higher socioeconomic status mothers. Breast pain, lack of support, and maternal skepticism about breastfeeding benefits were barriers; the latter was a recurrent theme among nonbreastfeeding mothers. CONCLUSIONS: While bedsharing is associated with breastfeeding in lower socioeconomic groups, it is not in higher socioeconomic African American groups. Skepticism about breastfeeding benefits may contribute to low breastfeeding rates in African Americans. PMID- 25139665 TI - Copper-mediated C6-selective dehydrogenative heteroarylation of 2-pyridones with 1,3-azoles. AB - A copper-mediated C6-selective dehydrogenative heteroarylation of 2-pyridones with 1,3-azoles has been developed. The reaction proceeded smoothly by twofold C H cleavage even in the absence of noble-metal catalysts. The observed site selectivity was directed by a pyridyl substituent on the nitrogen atom of the pyridone ring. This directing group was readily removed after the coupling event, thus leading to 2-pyridone derivatives with a free N-H group. Moreover, in some cases, catalytic turnover of the Cu salt was also possible with the ideal terminal oxidant: molecular oxygen in air. PMID- 25139666 TI - Family based genome-wide copy number scan identifies complex rearrangements at 17q21.31 in dyslexics. AB - Developmental dyslexia (DD) is a complex heritable disorder with unexpected difficulty in learning to read and spell despite adequate intelligence, education, environment, and normal senses. We performed genome-wide screening for copy number variations (CNVs) in 10 large Indian dyslexic families using Affymetrix Genome-Wide Human SNP Array 6.0. Results revealed the complex genomic rearrangements due to one non-contiguous deletion and five contiguous micro duplications and micro deletions at 17q21.31 region in three dyslexic families. CNVs in this region harbor the genes KIAA1267, LRRC37A, ARL17A/B, NSFP1, and NSF. The CNVs in case 1 and case 2 at this locus were found to be in homozygous state and case 3 was a de novo CNV. These CNVs were found with at least one CNV having a common break and end points in the parents. This cluster of genes containing NSF is implicated in learning, cognition, and memory, though not formally associated with dyslexia. Molecular network analysis of these and other dyslexia related module genes suggests NSF and other genes to be associated with cellular/vesicular membrane fusion and synaptic transmission. Thus, we suggest that NSF in this cluster would be the nearest gene responsible for the learning disability phenotype. PMID- 25139668 TI - The role of parents in children's school life: student motivation and socio emotional functioning. PMID- 25139667 TI - Comprehensive disease control (CDC): what does achieving CDC mean for patients with rheumatoid arthritis? AB - BACKGROUND: This study assessed the impact of simultaneous achievement of clinical, functional and structural efficacy, herein referred to as comprehensive disease control (CDC), on short-term and long-term work-related outcomes, health related quality of life (HRQoL), pain and fatigue. METHODS: Data were pooled from three randomised trials of adalimumab plus methotrexate for treatment of early stage or late-stage rheumatoid arthritis (RA). CDC was defined as 28-joint Disease Activity Score using C reactive protein <2.6, Health Assessment Questionnaire <0.5 and change from baseline in modified Total Sharp Score <=0.5. Changes in scores at weeks 26 and 52 for work-related outcomes, Short Form 36 (SF 36) physical (PCS) and mental component scores (MCS), a Visual Analogue Scale measuring pain (VAS-Pain) and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) were compared between patient groups defined by achievement of CDC at week 26 using linear regression with adjustment for baseline scores. RESULTS: Patients with RA who achieved CDC at week 26 (n=200) had significantly greater improvements in VAS-Pain (46.9 vs 26.9; p<0.0001), FACIT-F (13.3 vs 7.5; p<0.0001), SF-36 PCS (19.7 vs 8.9; p<0.0001) and SF-36 MCS (8.1 vs 5.0; p=0.0004) than those who did not (n=1267). Results were consistent at week 52 and among methotrexate-naive patients with early RA, methotrexate-experienced patients with late-stage RA and patients with inadequate response to methotrexate. CONCLUSIONS: Patients with RA who achieved CDC at week 26 had improved short-term and long term HRQoL, pain, fatigue and work-related outcomes compared with patients who do not. These results demonstrate that the joint achievement of all CDC components provides meaningful benefits to patients. TRIAL REGISTRATION NUMBERS: DE019: NCT00195702, PREMIER: NCT00195702, OPTIMA: NCT00195702. PMID- 25139669 TI - Production of transgenic dairy goat expressing human alpha-lactalbumin by somatic cell nuclear transfer. AB - Production of human alpha-lactalbumin (halpha-LA) transgenic cloned dairy goats has great potential in improving the nutritional value and perhaps increasing the yield of dairy goat milk. Here, a mammary-specific expression vector 5A, harboring goat beta-lactoglobulin (betaLG) promoter, the halpha-LA gene, neo(r) and EGFP dual markers, was constructed. Then, it was effectively transfected into goat mammary epithelial cells (GMECs) and the expression of halpha-LA was investigated. Both the halpha-LA transcript and protein were detected in the transfected GMECs after the induction of hormonal signals. In addition, the 5A vector was introduced into dairy goat fetal fibroblasts (transfection efficiency ~60-70%) to prepare competent transgenic donor cells. A total of 121 transgenic fibroblast clones were isolated by 96-well cell culture plates and screened with nested-PCR amplification and EGFP fluorescence. After being frozen for 8 months, the transgenic cells still showed high viabilities, verifying their ability as donor cells. Dairy goat cloned embryos were produced from these halpha-LA transgenic donor cells by somatic cell nuclear transfer (SCNT), and the rates of fusion, cleavage, and the development to blastocyst stages were 81.8, 84.4, and 20.0%, respectively. A total of 726 reconstructed embryos derived from the transgenic cells were transferred to 74 recipients and pregnancy was confirmed at 90 days in 12 goats. Of six female kids born, two carried halpha-LA and the halpha-LA protein was detected in their milk. This study provides an effective system to prepare SCNT donor cells and transgenic animals for human recombinant proteins. PMID- 25139670 TI - Skeletal defects in Osterix-Cre transgenic mice. AB - Cre/loxP recombination is a powerful strategy widely used for in vivo conditional gene targeting. This technique has made possible many important discoveries of gene function in normal and disease biology. However, due to the transgenic nature of most Cre mouse strains undesired phenotypes occasionally occur in Cre mice. Here we report skeletal defects in Osterix-Cre (Osx-Cre) transgenic mice including delayed calvarial ossification and fracture calluses at multiple skeletal sites. These data suggest that Osx-Cre containing controls should be used for both in vivo and in vitro skeletal analyses of conditional knockout mice generated with this Osx-Cre mouse strain. PMID- 25139671 TI - Cytological Features of Carcinosarcoma ex Pleomorphic Adenoma of the Parotid Gland: A Case Report. AB - BACKGROUND: Carcinosarcoma of the salivary gland is an extremely rare tumor composed of carcinomatous and sarcomatoid components. This report describes the cytological and pathological findings of a case of carcinosarcoma ex pleomorphic adenoma arising in the right parotid gland. CASE: A 47-year-old female visited a hospital with swelling of the right parotid region, slight pain and facial palsy. Fine-needle aspiration smears showed both clustered epithelium-like cells and singly scattered cells in a necrotic background. The cells, especially the latter, exhibited significant cellular pleomorphism and had irregularly shaped nuclei. Myxoid stroma-like cell clusters without cellular atypism were also seen. The right parotid gland was resected, and the tumor tissue was histologically diagnosed as carcinosarcoma ex pleomorphic adenoma. CONCLUSION: The cytological findings of carcinosarcoma ex pleomorphic adenoma have been reported in very few cases. In the present case, various components, including the presence of atypical epithelium-like cell clusters and singly scattered atypical cells with stromal components on cytological specimens, led to consideration of the diagnosis of carcinosarcoma ex pleomorphic adenoma. PMID- 25139672 TI - CSF levels of Abeta1-38/Abeta1-40/Abeta1-42 and (11)C PiB-PET studies in three clinical variants of primary progressive aphasia and Alzheimer's disease. AB - Primary progressive aphasia (PPA) is a cognitive syndrome characterized by progressive and isolated language impairments due to neurodegenerative diseases. Recently, an international group of experts published a Consensus Classification of the three PPA clinical variants (naPPA, svPPA and lvPPA). We analyzed 24 patients with PPA by cognitive functions, neuroimaging (MRI, (99 m)Tc ECD-SPECT, (11)C PiB-PET and FDG-PET) and cerebrospinal fluid (CSF) analysis (ptau-181, Abeta1-42, Abeta1-40 and Abeta1-38), to elucidate relationships between neuroimaging studies and biochemical findings in the three PPA clinical variants. Cognitive and speech functions were measured by mini-mental state examination and standard language test of aphasia. The patients with lvPPA showed significant decreases in CSF Abeta1-42 and ratios of Abeta1-42/Abeta1-40 and Abeta1-42/Abeta1 38, and significant increases in CSF ptau-181 and ratios of ptau-181/Abeta1-42 and ptau-181/Abeta1-38; these findings were similar to those of patients with Alzheimer's disease (AD). We observed a higher frequency of the ApoE epsilon4 allele in the lvPPA patients relative to the two other PPA variants. In (11)C PiB PET of lvPPA patients, PiB positive findings were detected in cortices of frontal, temporal and parietal lobes and the posterior cingulate, where massive Abeta may accumulate due to AD. Our results of AD-CSF markers including Abeta1-38 and (11)C PiB-PET in the lvPPA patients demonstrate a common pathological mechanism with the occurrence of AD. PMID- 25139673 TI - Homology modeling, molecular dynamics, and docking studies of pattern-recognition transmembrane protein-lipopolysaccharide and beta-1,3 glucan-binding protein from Fenneropenaeus indicus. AB - Lipopolysaccharide and beta-1,3 glucan-binding protein (LGBP) is a family of pattern-recognition transmembrane proteins (PRPs) which plays a vital role in the immune mechanism of crustaceans in adverse conditions. Fenneropenaeus indicus LGBP-deduced amino acid has conserved potential recognition motif for beta-1,3 linkages of polysaccharides and putative RGD (Arg-Gly-Asp) cell adhesion sites for the activation of innate defense mechanism. In order to understand the stimulating activity of beta-1,3 glucan (beta-glucan) and its interaction with LGBP, a 3D model of LGBP is generated. Molecular docking is performed with this model, and the results indicate Arg71 with strong hydrogen bond from RGD domain of LGBP. Moreover, from the docking studies, we also suggest that Arg34, Lys68, Val135, and Ala146 in LGBP are important amino acid residues in binding as they have strong bonding interaction in the active site of LGBP. In our in vitro studies, yeast agglutination results suggest that shrimp F. indicus LGBP possesses sugar binding and recognition sites in its structure, which is responsible for agglutination reaction. Our results were synchronized with the already reported evidence both in vivo and in vitro experiments. This investigation may be valuable for further experimental investigation in the synthesis of novel immunomodulator. PMID- 25139674 TI - Progression of muscle histopathology but not of spliceopathy in myotonic dystrophy type 2. AB - Myotonic dystrophy type 2 (DM2) is an autosomal dominant progressive disease involving skeletal and cardiac muscle and brain. It is caused by a tetranucleotide repeat within the first intron of the CNBP gene that leads to an alteration of the alternative splicing of several genes. To understand the molecular mechanisms that play a role in DM2 progression, the evolution of skeletal muscle histopathology and biomolecular findings in successive biopsies have been studied. Biceps brachii biopsies from 5 DM2 patients who underwent two successive biopsies at different years of age have been used. Muscle histopathology has been assessed on sections immunostained with fast or slow myosin. FISH in combination with MBNL1-immunofluorescence has been performed to evaluate ribonuclear inclusion and MBNL1 foci dimensions in myonuclei. Gene and protein expression and alteration of alternative splicing of several genes have been evaluated over time. All DM2 patients examined show a worsening of muscle histopathology and an increase of foci dimensions over time. The progressive worsening of myotonia in DM2 patients may be due to the decrease of CLCN1 mRNA observed in all patients examined. However, a worsening of alternative splicing alterations has not been evidenced over time. The data obtained in this study confirm that DM2 is a slow progression disease since histological and biomolecular alterations observed in skeletal muscle are minimal even after 10 year interval. The data indicate that muscle morphological alterations evolve more rapidly over time than the molecular changes thus indicating that muscle biopsy is a more sensitive tool than biomolecular markers to assess disease progression at muscle level. PMID- 25139675 TI - Beneficial effect of cilostazol-mediated neuronal repair following trimethyltin induced neuronal loss in the dentate gyrus. AB - Cilostazol acts as an antiplatelet agent and has other pleiotropic effects based on phosphodiesterase-3-dependent mechanisms. We evaluated whether cilostazol would have a beneficial effect on neuronal repair following hippocampal neuronal damage by using a mouse model of trimethyltin (TMT)-induced neuronal loss/self repair in the hippocampal dentate gyrus [Ogita et al. (2005) J Neurosci Res 82:609-621]; these mice will hereafter be referred to as impaired animals. A single treatment with cilostazol (10 mg/kg, i.p.) produced no significant change in the number of 5-bromo-2'-deoxyuridine (BrdU)-incorporating cells in the dentate granule cell layer (GCL) or subgranular zone on day 3 after TMT treatment. However, chronic treatment with cilostazol on days 3-15 posttreatment resulted in an increase in the number of BrdU-incorporating cells in the dentate GCL of the impaired animals, and these cells were positive for neuronal nuclear antigen or doublecortin. Cilostazol was effective in elevating the level of phosphorylated cyclic adrenosine monophosphate response element-binding protein (pCREB) in the dentate gyrus of impaired animals. The results of a forced swimming test revealed that the chronic treatment with cilostazol improved the depression-like behavior seen in the impaired animals. In the cultures of hippocampal neural stem/progenitor cells, exposure to cilostazol produced not only enhancement of proliferation activity but also elevation of pCREB levels. Taken together, our data suggest that cilostazol has a beneficial effect on neuronal repair following neuronal loss in the dentate gyrus through promotion of proliferation and/or neuronal differentiation of neural progenitor cells in the subgranular zone. PMID- 25139676 TI - Robotic-assisted fluorescence sentinel lymph node mapping using multimodal image guidance in an animal model. AB - OBJECTIVE: To investigate positron emission tomography/computed tomography (PET/CT) preoperative imaging and intraoperative detection of a fluorescent labeled receptor-targeted radiopharmaceutical in a prostate cancer animal model. MATERIALS AND METHODS: Three male beagle dogs underwent an intraprostatic injection of fluorescent-tagged tilmanocept, radiolabeled with both gallium Ga-68 and technetium Tc-99m. One hour after injection, a pelvic PET/CT scan was performed for preoperative sentinel lymph node (SLN) mapping. The definition of SLN was a standardized uptake value that exceeded 5% of the lymph node with the highest standardized uptake value. Thirty-six hours later, we performed robotic assisted SLN dissection using a fluorescence-capable camera system. Fluorescent lymph nodes were clipped, the abdomen was opened, and the pelvic and retroperitoneal nodes were excised. All excised nodal packets were assayed by in vitro nuclear counting and reported as the percentage of injected dose. RESULTS: Preoperative PET/CT imaging identified a median of 3 SLNs per animal. All SLNs (100%) identified by the PET/CT were fluorescent during robotic-assisted lymph node dissection. Of all fluorescent nodes visualized by the camera system, 9 of 12 nodes (75%) satisfied the 5% rule defined by the PET/CT scan. The 2 lymph nodes that did not qualify accumulated <0.002% of the injected dose. CONCLUSION: Fluorescent-labeled tilmanocept has optimal logistic properties to obtain preoperative PET/CT and subsequent real-time intraoperative confirmation during robotic-assisted SLN dissection. PMID- 25139677 TI - High-throughput nucleoside phosphate monitoring in mammalian cell fed-batch cultivation using quantitative matrix-assisted laser desorption/ionization time of-flight mass spectrometry. AB - Current methods for monitoring multiple intracellular metabolite levels in parallel are limited in sample throughput capabilities and analyte selectivity. This article presents a novel high-throughput method based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) for monitoring intracellular metabolite levels in fed-batch processes. The MALDI-TOF MS method presented here is based on a new microarray sample target and allows the detection of nucleoside phosphates and various other metabolites using stable isotope labeled internal standards. With short sample preparation steps and thus high sample throughput capabilities, the method is suitable for monitoring mammalian cell cultures, such as antibody producing hybridoma cell lines in industrial environments. The method is capable of reducing the runtime of standard LC-UV methods to approximately 1 min per sample (including 10 technical replicates). Its performance is exemplarily demonstrated in an 8-day monitoring experiment of independently controlled fed-batches, containing an antibody producing mouse hybridoma cell culture. The monitoring profiles clearly confirmed differences between cultivation conditions. Hypothermia and hyperosmolarity were studied in four bioreactors, where hypothermia was found to have a positive effect on the longevity of the cell culture, whereas hyperosmolarity lead to an arrest of cell proliferation. The results are in good agreement with HPLC-UV cross validation experiments. Subsequent principal component analysis (PCA) clearly separates the different bioreactor conditions based on the measured mass spectral profiles. This method is not limited to any cell line and can be applied as a process analytical tool in biotechnological processes. PMID- 25139678 TI - Structural insights into binding of small molecule inhibitors to Enhancer of Zeste Homolog 2. AB - Enhancer of Zeste Homolog 2 (EZH2) is a SET domain protein lysine methyltransferase (PKMT) which has recently emerged as a chemically tractable and therapeutically promising epigenetic target, evidenced by the discovery and characterization of potent and highly selective EZH2 inhibitors. However, no experimental structures of the inhibitors co-crystallized to EZH2 have been resolved, and the structural basis for their activity and selectivity remains unknown. Considering the need to minimize cross-reactivity between prospective PKMT inhibitors, much can be learned from understanding the molecular basis for selective inhibition of EZH2. Thus, to elucidate the binding of small-molecule inhibitors to EZH2, we have developed a model of its fully-formed cofactor binding site and used it to carry out molecular dynamics simulations of protein ligand complexes, followed by molecular mechanics/generalized born surface area calculations. The obtained results are in good agreement with biochemical inhibition data and reflect the structure-activity relationships of known ligands. Our findings suggest that the variable and flexible post-SET domain plays an important role in inhibitor binding, allowing possibly distinct binding modes of inhibitors with only small variations in their structure. Insights from this study present a good basis for design of novel and optimization of existing compounds targeting the cofactor binding site of EZH2. PMID- 25139679 TI - Antimicrobial activity of alexidine, chlorhexidine and cetrimide against Streptococcus mutans biofilm. AB - BACKGROUND: The use of antimicrobial solutions has been recommended to disinfect demineralized dentin prior to placing the filling material. The aim of this study was to evaluate the ability of several antimicrobials in controlling Streptococcus mutans (SM) biofilm formed in dentin. METHODS: Antimicrobial activity of 0.2% and 2% chlorhexidine (CHX), 0.2% cetrimide (CTR) and 0.2%, 0.5%, 1% and 2% alexidine (ALX) was assayed on 1-week SM biofilm formed on standardized coronal dentin blocks. Results of SM biofilm antimicrobial activity by different protocols were expressed as the kill percentage of biofilm and the term "eradication" was used to denote the kill of 100% of the bacterial population. To compare the efficacies of the different protocols the Student t test was used, previously subjecting data to the Anscombe transformation. RESULTS: All ALX concentrations tested and 0.2% CTR achieved a kill percentage higher than 99%, followed by 2% CHX with percentages above 96% (no statistically significant difference among them). Whereas 2% ALX and 0.2% CTR respectively showed eradication in 10 and 9 of the twelve specimens, 0.2% CHX did not produce eradication in any case. CONCLUSIONS: The present study shows that, when used for one minute, 2% and 1% alexidine, and 0.2% cetrimide, achieve eradication of Streptococcus mutans biofilm in most specimens when applied to a dentin volumetric model. PMID- 25139680 TI - Food addiction in a Spanish sample of eating disorders: DSM-5 diagnostic subtype differentiation and validation data. AB - Although the concept of 'food addiction' (FA) has raised growing interest because of evidence for similarities between substance dependence and excessive food intake, there is a lack of studies that explore this construct among the wide spectrum of eating disorders (EDs). Besides providing validation scores of a Spanish version of the Yale FA Scale (YFAS-S), this study examined the prevalence of 'FA' among ED subtypes compared with healthy-eating controls (HCs) and the association between 'FA' scores, eating symptomatology and general psychopathology. A sample of 125 adult women with ED, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders 5 criteria, and 82 healthy eating women participated in the study. All participants were assessed with the YFAS-S, the ED Inventory-2 and the Symptom Checklist-Revised. Results showed that the internal structure of the one-dimensional solution for the YFAS-S was very good (alpha = 0.95). The YFAS-S has a good discriminative capacity to differentiate between ED and controls (specificity = 97.6% and sensitivity (Se) = 72.8%; area under receiver operating characteristic curve = 0.90) and a good Se to screen for specific ED subtypes. YFAS-S scores were associated with higher levels of negative affect and depression, higher general psychopathology, more severe eating pathology and greater body mass index. When comparing the prevalence of 'FA' between ED subtypes, the lowest prevalence of 'FA', measured with the YFAS-S, was for the anorexia nervosa (AN) restrictive subtype with 50%, and the highest was for the AN binge-purging subtype (85.7%), followed by bulimia nervosa (81.5%) and binge eating disorder (76.9%). In conclusion, higher YFAS-S scores are associated with bingeing ED-subtype patients and with more eating severity and psychopathology. Although the 'FA' construct is able to differentiate between ED and HC, it needs to be further explored. PMID- 25139681 TI - Factors associated with exclusive breastfeeding at hospital discharge in rural Western Australia. AB - BACKGROUND: Breastfeeding is accepted as the best way of feeding infants, and health authorities recommend exclusive breastfeeding to around 6 months of age, but despite the evidence of its benefits, few mothers meet this goal. Infants who are exclusively breastfed in the early postpartum period are more likely to continue breastfeeding at 6 and 12 months, reinforcing the role that Baby Friendly hospital practices play in supporting exclusive breastfeeding. OBJECTIVES: This study aimed to determine the rate of breastfeeding initiation and identify the factors associated with exclusive breastfeeding at discharge from hospital for rural mothers. METHODS: The prospective cohort study recruited 489 women from hospitals in regional Western Australia following the birth of their infant. Breastfeeding exclusivity at discharge was assessed based on mothers' self-reported infant feeding behavior during her hospital stay. The self administered baseline questionnaire was completed by 427 mothers. RESULTS: Breastfeeding was initiated by 97.7% of the mothers in this cohort, with 82.7% exclusively breastfeeding at hospital discharge. The odds of exclusive breastfeeding at discharge were more than 4 times higher for women whose infants did not require admission to the special care nursery (adjusted odds ratio [aOR] = 4.43; 95% confidence interval [CI], 1.98-9.99). Demand feeding (aOR = 3.33; 95% CI, 1.59-6.95) and 24-hour rooming-in (aOR = 2.31; 95% CI, 1.15-4.62) were also significant positive factors. CONCLUSION: The findings suggest that hospital practices are strong predictors of exclusive breastfeeding. Greater emphasis on Baby-Friendly hospital practices in the early postpartum period may help the establishment of exclusive breastfeeding, assisting rural mothers to reach established international breastfeeding recommendations. PMID- 25139682 TI - Temperature-dependent photoluminescence in light-emitting diodes. AB - Temperature-dependent photoluminescence (TDPL), one of the most effective and powerful optical characterisation methods, is widely used to investigate carrier transport and localized states in semiconductor materials. Resonant excitation and non-resonant excitation are the two primary methods of researching this issue. In this study, the application ranges of the different excitation modes are confirmed by analysing the TDPL characteristics of GaN-based light-emitting diodes. For resonant excitation, the carriers are generated only in the quantum wells, and the TDPL features effectively reflect the intrinsic photoluminescence characteristics within the wells and offer certain advantages in characterising localized states and the quality of the wells. For non-resonant excitation, both the wells and barriers are excited, and the carriers that drift from the barriers can contribute to the luminescence under the driving force of the built-in field, which causes the existing equations to become inapplicable. Thus, non-resonant excitation is more suitable than resonant excitation for studying carrier transport dynamics and evaluating the internal quantum efficiency. The experimental technique described herein provides fundamental new insights into the selection of the most appropriate excitation mode for the experimental analysis of carrier transport and localized states in p-n junction devices. PMID- 25139683 TI - Binding kinetics, potency, and selectivity of the hepatitis C virus NS3 protease inhibitors GS-9256 and vedroprevir. AB - BACKGROUND: GS-9256 and vedroprevir are inhibitors of the hepatitis C virus NS3 protease enzyme, an important drug target. The potency, selectivity, and binding kinetics of the two compounds were determined using in vitro biochemical assays. METHODS: Potency of the compounds against NS3 protease and selectivity against a panel of mammalian proteases were determined through steady-state enzyme kinetics. Binding kinetics were determined using stopped-flow techniques. Dissociation rates were measured using dilution methods. RESULTS: GS-9256 and vedroprevir had measured Ki values of 89 pM and 410 pM, respectively, against genotype 1b NS3 protease; Ki values were higher against genotype 2a (2.8 nM and 39 nM) and genotype 3 proteases (104 nM and 319 nM) for GS-9256 and vedroprevir, respectively. Selectivity of GS-9256 and vedroprevir was >10,000-fold against all tested off-target proteases. Association rate constants of 4*10(5)M(-1)s(-1) and 1*10(6)M(-1)s(-1), respectively, were measured, and dissociation rate constants of 4.8*10(-5)s(-1) and 2.6*10(-4)s(-1) were determined. CONCLUSIONS: GS-9256 and vedroprevir are potent inhibitors of NS3 protease with high selectivity against off-target proteases. They have rapid association kinetics and slow dissociation kinetics. GENERAL SIGNIFICANCE: The NS3 protease is a key drug target for the treatment of hepatitis C. The potency, selectivity, and binding kinetics of GS 9256 and vedroprevir constitute a biochemical profile that supports the evaluation of these compounds in combination with other direct-acting antivirals in clinical trials for hepatitis C. PMID- 25139684 TI - Clostridium difficile infection: an undeniably common problem among hematopoietic transplant recipients. PMID- 25139688 TI - Risk of premature menopause after treatment for Hodgkin's lymphoma. PMID- 25139687 TI - Risk of premature menopause after treatment for Hodgkin's lymphoma. AB - BACKGROUND: Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been relatively small, and knowledge about these risks is limited. METHODS: Nonsurgical menopause risk was analyzed in 2127 women treated for HL in England and Wales at ages younger than 36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were estimated using Cox regression, modified Poisson regression, and competing risks. All statistical tests were two-sided. RESULTS: During follow-up, 605 patients underwent nonsurgical menopause before age 40 years. Risk of premature menopause increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not statistically significantly raised after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Menopause generally occurred sooner after ovarian radiotherapy (62.5% within five years of >=5 Gy treatment) and BEAM (50.9% within five years) than after alkylating chemotherapy (24.2% within five years of >=6 cycles), and after treatment at older than at younger ages. Cumulative risk of menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely supradiaphragmatic radiotherapy. Tables of individualized risk information for patients by future period, treatment type, dose and age are provided. CONCLUSIONS: Patients treated with HL need to plan intended pregnancies using personalized information on their risk of menopause by different future time points. PMID- 25139689 TI - Pre-transplant achievement of negativity in minimal residual disease and French American-British L1 morphology predict superior outcome after allogeneic transplant for Philadelphia chromosome positive acute lymphoblastic leukemia: an analysis of Southeast Asian patients. AB - To better understand predictive factors and improve the clinical outcome of allogeneic transplant for patients with Philadelphia positive acute lymphoblastic leukemia, we analyzed 67 Southeast Asian patients transplanted in our institutions. Multivariate analysis showed that disease status before transplant, year of transplant and, interestingly, French-American-British (FAB) subtype had a significant impact on overall survival (OS) and non-relapse mortality. Patients who were minimal residual disease (MRD) negative at transplant had a 3-year OS of 73% compared to those who were MRD positive (45%) and refractory (0%). The 3-year cumulative incidence of relapse was 18% and 36% for the MRD negative and positive groups, respectively. FAB L1 subtype had a significantly superior 3-year OS of 63% vs. 29% for L2 subtype. Pre-transplant use of a tyrosine kinase inhibitor significantly improved outcomes in univariate but not multivariate analysis, as it served to induce more patients into MRD negativity, which was the factor that directly improved transplant outcome. PMID- 25139690 TI - Absolute lymphocyte count is unrelated to overall survival in newly diagnosed elderly patients with multiple myeloma treated with immunomodulatory drugs. PMID- 25139691 TI - Outcome of pediatric patients with lymphoma following stem cell transplant: a single institution report. AB - Hematopoietic stem cell transplant (HSCT) is recommended for pediatric patients with relapsed/refractory lymphoma even though the evidence for this is limited. We retrospectively reviewed records of 57 patients (29 Hodgkin lymphoma [HL], 28 non-Hodgkin lymphoma [NHL]) who underwent HSCT between 1995 and 2012. All demonstrated chemoresponsiveness prior to HSCT and 44 patients had a complete response. All underwent myeloablative conditioning, 38 chemotherapy-based and 19 total body irradiation-based. Forty-one patients received autologous and 16 allogeneic HSCT. Twelve (21%) died within 100 days post-HSCT, and 25 patients relapsed at a median of 1.6 months post-HSCT. Three patients developed second malignant neoplasms. Five-year overall survival (OS) was 50.5% and event-free survival (EFS) was 43.4%. Outcomes for HL were significantly better than those for NHL (OS 61.9% vs. 38.7% [p = 0.005] and EFS 60.4% vs. 26% [p = 0.008]). In summary, approximately half of all pediatric patients with lymphoma who failed first-line therapy and demonstrated chemosensitivity to second-line therapy can be salvaged with HSCT. PMID- 25139692 TI - Methylenetetrahydrofolate reductase 677 C> T polymorphism is associated with acute myeloid leukemia. PMID- 25139693 TI - Voriconazole toxicity masquerading as septic shock. PMID- 25139694 TI - Real-world cost-effectiveness in chronic myeloid leukemia: the price of success during four decades of development from non-targeted treatment to imatinib. AB - Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML). We evaluated clinical outcome and cost-effectiveness, using Swedish registry data based on patients with CML diagnosed 1973-2008. Outcome from three time periods (I: 1973-1979; II: 1991-1997; III: 2002-2008) associated with symptomatic treatment, interferon-alpha/stem cell transplant and implementation of imatinib, respectively, were compared and a lifetime cost-effectiveness model developed. Survival data from population registries, estimated resource use from clinical practice and quality of life estimates were employed. Substantial health gains were noted over time, paralleled by increased treatment costs. Median survival was 1.9, 4.0 and 13 years during the respective time periods. The incremental cost-effectiveness ratio (ICER) between periods III and II was ?52,700 per quality-adjusted life year (QALY) gained. An estimated 80% price reduction of imatinib, related to patent expiry, would reduce this ICER to ?22,700. Our data from four decades reveal dramatically improved survival in CML, paralleled by ICER levels generally accepted by health authorities. PMID- 25139695 TI - Understanding the polar mechanism of the ene reaction. A DFT study. AB - The molecular mechanism of ene reactions has been characterised by DFT methods at the MPWB1K/6-311G(d,p) level of theory. Most reactions take place along a two stage one-step mechanism in which the C-C bond formation takes place before the hydrogen transfer process. A very good correlation between the polar character of the reaction measured by the global electron density transfer at the transition state and the activation energy has been found. This behaviour allows establishing a useful classification of ene reactions in N-ene having a very high activation energy, P-ene reactions having activation energies between 35 and 20 kcal mol(-1), and H-ene reactions having activation energies below 20 kcal mol( 1). ELF topological analysis allows the characterisation of the two-stage one step mechanism associated with a two-centre nucleophilic/electrophilic interaction. Formation of the C-C single bond is achieved by the C-to-C coupling of two pseudoradical centres formed at the two interacting carbon atoms in the first stage of the reaction. This topological analysis establishes that bonding changes are non-concerted. Finally, a DFT reactivity analysis makes it possible to characterise the electrophilic/nucleophilic behaviour of the reagents involved in ene reactions, and consequently, to predict the feasibility of ene reactions. PMID- 25139698 TI - Effect of trunk-to-head bathing on physiological responses in newborns. AB - OBJECTIVE: To determine the effect of trunk-to-head bathing versus the traditional head-to-trunk bathing on newborns' body temperature, heart rate, and oxygen saturation. DESIGN: A prospective, two-group, quasi-experimental repeated measures design. SETTING: A newborn nursery in an urban university hospital. PARTICIPANTS: Sixty-two healthy full-term newborns. METHODS: Newborns were randomly assigned to two groups. The newborns in the experimental group were bathed from trunk to head; those in the control group were bathed from head to trunk. Measurements of body temperature, heart rate, and oxygen saturation were obtained at four time points: before the bath, immediately after the bath, 30 minutes after the bath, and 60 minutes after the bath. RESULTS: No significant differences in body temperature, heart rate, or oxygen saturation were observed between groups. However, body temperature was significantly different across measurement times, and there was a significant interaction between group and measurement time. The mean body temperature dropped 0.2 degrees C after bathing in both groups, but the experimental group returned to their initial body temperature more rapidly than the control group. CONCLUSION: These findings suggest that newborns who were bathed from trunk to head and whose heads were wet for shorter periods of time benefited with a more rapid recovery of body temperature and decreased heat loss due to evaporation. PMID- 25139696 TI - A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation? AB - AIMS: Hyponatraemia is one of the major adverse effects of thiazide and thiazide like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. METHODS: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. RESULTS: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m( 2) . Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. CONCLUSIONS: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7-14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required. PMID- 25139699 TI - Circulating SFRP5 levels are elevated in drug-naive recently diagnosed type 2 diabetic patients as compared with prediabetic subjects and controls. AB - BACKGROUND: Secreted frizzled-related protein 5 (SFRP5) has been linked to obesity. Results are conflicting regarding its association with type 2 diabetes (T2D) in humans. We aimed to investigate circulating SFRP5 in prediabetes and T2D and its potential association with parameters of insulin resistance and beta-cell function. METHODS: We studied 70 drug-naive T2D patients, 70 prediabetic subjects and 70 controls. All subjects were body mass index matched to the T2D patients and overweight or obese. SFRP5, hormones and cytokines levels were measured by ELISA. RESULTS: Serum SFRP5 levels were elevated in T2D patients as compared with prediabetic subjects (median 15.6, interquartile range [9-24.5] ng/mL vs 9.8 [5 14.2] ng/mL, p < 0.001, respectively) and controls (15.6 [9-24.5] ng/mL vs 10.4 [6.7-16.6] ng/mL, P < 0.001, respectively). No differences were found in serum SFRP5 levels between prediabetic subjects and controls (9.8 [5-14.2] ng/mL vs 10.4 [6.7-16.6] ng/mL, p = 0.472, respectively). After adjusting for potential confounders (age, gender, body mass index, triglycerides, high-density lipoprotein cholesterol and blood pressure), T2D was still associated with higher values of SFRP5 as compared with prediabetes in multinomial logistic regression analysis (fully adjusted odds ratio 3.50, 95% confidence interval 1.40-8.79, p = 0.008). The association was more subtle when comparing T2D with normal glucose tolerance state (fully adjusted odds ratio 2.18, 95% confidence interval 0.91 5.21, p = 0.078). CONCLUSIONS: Circulating SFRP5 levels were independently associated with T2D as compared with prediabetes and normal glucose tolerance state. PMID- 25139700 TI - "You're in that realm of unpredictability": mateship, loyalty, and men challenging men who use domestic violence against women. AB - This study reports on discourse analysis of transcripts from focus group discussions held with 28 "ordinary" men about domestic violence. Two broad "mateship" themes emerged: (a) a strong "mateship" discourse that produced public/private boundaries around discussions about intimate heterosexual relationships. Policed by the threat of violence, these boundaries prevented some men from challenging men about their violence. (b) "Loyalty to mates" discourses constituted attention to men's violence against women as threatening the moral integrity of all men. Finally, some men positioned themselves against men's domestic violence, distinguishing their masculinity from men who abuse women. Implications for prevention campaigns are discussed. PMID- 25139701 TI - Preparedness of final-year Turkish nursing students for work as a professional nurse. AB - AIMS AND OBJECTIVES: To determine the preparedness levels of final-year Turkish nursing students starting their careers as professional nurses. BACKGROUND: The transition from nursing student to professional nurse is challenging. One of the ways to help facilitate this transition is to determine how well students are prepared to start work. There are limited, but conflicting, results on this topic. DESIGN: Mixed-methods study. METHODS: Undergraduate nursing students (n = 4490) in their final year of study from 74 Turkish universities were eligible to participate in this study. Of these, 1804 total students participated from 38 randomly selected universities. Data were collected through an investigator developed questionnaire (n = 1804) and focus group interviews (n = 57). RESULTS: Students felt highly prepared to start work (57.6%). Those who were older, male, graduates of a vocational high school or already working as a nurse felt most prepared. Students who felt that their education preparation and resources were adequate felt more prepared. Focus group interviews revealed that students felt confident in their knowledge of educational theory, but not in clinical skills. CONCLUSIONS: Students may have felt prepared to start work, but insufficient clinical experience probably contributed to a lack of confidence in their skills. The resources of the school, the quality of the education, and the clinical practice environments were considered most important for the students' perceived preparedness levels. RELEVANCE TO CLINICAL PRACTICE: An undergraduate education provides the foundation for successful nurse preparation. A good clinical environment along with a high-quality education programme can help give students more confidence in their skills when they join the nursing workforce. Internship or residency programmes may also facilitate this learning. This is extremely important for safe, high-quality patient care. PMID- 25139702 TI - Deviation of sonographic estimated fetal weight from actual birth weight in two consecutive pregnancies of the same parturients. AB - OBJECTIVE: To determine whether maternal features affect the accuracy of sonographic estimated fetal weight (SEFW) by evaluating the consistency of the systematic error of SEFW with regards to the birth weight (BW) in two consecutive pregnancies of the same gravida. METHODS: The cohort included women with SEFW within 1 week of delivery (32-42 weeks' gestation) in two consecutive singleton pregnancies from 2007 to 2012. The systematic error was calculated as (SEFW - BW)/BW * 100 and expressed as a percentage of the BW. RESULTS: A total of 636 pregnancies (318 gravidas) were eligible for analysis. The BW and SEFW were correlated in both first examined (r = 0.873, p < 0.001) and consecutive (r = 0.843, p < 0.001) pregnancies. There was a significant difference in mean systematic error between first examined and consecutive pregnancies (3.13 +/- 8.95 vs. 0.34 +/- 8.75%, p < 0.001), with a very weak correlation between the two (r = 0.135, p = 0.16). Nulliparity or multiparity at the first examined pregnancy was not found to be a significant factor, and in both groups the error was higher in the first examined pregnancy. There were no significant differences between parturients with a minor (10% and below) or major (>10%) difference in the systematic error between the two pregnancies. CONCLUSION: The systematic error between the SEFW and BW in two consecutive pregnancies is inconsistent, suggesting that it is unaffected by maternal biometric features. PMID- 25139703 TI - Staphylococcus aureus bio-products: new biological roles for a pleurodesis agent. PMID- 25139704 TI - [Acute jaw-thoracic pain and syncope in a 41-year-old man]. AB - A 41-year-old physically active man with no significant past medical history presented with sudden thoracic pain. The patient was referred to the next tertiary care hospital. A CT scan showed an ectasia of the ascending aorta with irregularities of the aortic wall without dissection. Despite initial refusal, the patient was referred to a university hospital with experience in aortic surgery. A triphase ECG-synchronized cardiothoracic flash protocol performed on a 256 line CT scanner confirmed an aortic intramural hematoma and a covered aortic perforation. Shortly afterwards the patient collapsed and had to be resuscitated. PMID- 25139705 TI - [Pharmacotherapy of solid tumors. New hopes and frustrations]. AB - Recent years have seen dramatic changes in the biological understanding and treatment of solid tumors. Based on the tumor biology, targeting agents have been developed which directly affect the underlying genetic or immunological changes found in specific tumor entities. Significant increases in survival have delivered the functional proof of the concept of targeted and immunological tumor therapy. The management and adherence of the patient as well as optimized cooperation with clinicians are decisive for the results of therapy and disease control.Several solid tumors are currently under investigation in clinical studies evaluating the (sequential) therapy with targeting and immunologically active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies, such as bevacizumab, specific antagonists, such as enzalutamide and immunological checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.Currently approved agents have dramatically changed the landscape of treatment options especially for prostate cancer. Such agents include hormone therapy with enzalutamide and abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib, sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer (crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor (regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has entered the stage of targeted therapy with the approval of nanoparticle albumin bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical trials are focusing on the best time point and sequence of therapy and also improvement in the management of these promising agents. PMID- 25139706 TI - [Acute pancreatitis: guideline-based diagnosis and treatment]. AB - Acute pancreatitis is most frequently of biliary or alcoholic origin and less frequently due to iatrogenic (ERCP, medication) or metabolic causes. Diagnosis is usually based on abdominal pain and elevation of serum lipase to more than three times the normal limit. Acute pancreatitis can either resolve quickly following an oedematous swelling or present as a severe necrotizing form. A major risk is the systemic inflammatory response syndrome (SIRS), which can cause multi-organ failure. Prediction of disease course is initially difficult, thus necessitating immediate therapy and regular re-evaluation. In order to prove or exclude biliary genesis, abdominal ultrasonography should first be performed and endoscopic ultrasound may also be required. Primary therapy includes rapid and correctly dosed fluid substitution. Biliary pancreatitis requires causal treatment. In the case of cholangitis, stone extraction must be performed immediately; in the absence of cholangitis, it might be advisable to wait for spontaneous stone clearance. Timely cholecystectomy is necessary in all cases of biliary pancreatitis. PMID- 25139707 TI - A review of methotrexate-associated hepatotoxicity. AB - Methotrexate is effective not only in treating psoriasis and rheumatoid arthritis but also various other disorders. The use of methotrexate has been somewhat limited by concerns regarding its adverse effects, including its potential for hepatotoxicity. The purpose of this article is to provide an overview of methotrexate-associated hepatotoxicity, including risk factors, pathogenesis and recommendations for monitoring it by US, UK and European guidelines, as well as providing a brief overview of its mechanism of action and of high-dose methotrexate. PMID- 25139708 TI - Considering economic analyses in the revision of the preventive vaccination law: a new direction for health policy-making in Japan? AB - Evidence of a significant vaccine policy shift can be witnessed not only in the number of new vaccines available in Japan but also in the way that vaccine policy is being formulated. In 2010, policy makers decided for the first time ever to commission economic analyses as a reference in their consideration of subsidy allocation. This research offers a first hand account of the recent changes in vaccine policies by examining the decision-making process from the perspective of the researchers commissioned to perform the economic evaluations. In order to understand the vaccine policy-making process, a review was made of all the documents that were distributed and discussed during the government committee meetings from February 2010 when the revision of the Preventive Vaccination Law was initially proposed to May 2012 when the final recommendations were made. Economic evaluations were conducted for seven vaccines under consideration in the routine immunization program (Haemophilus influenzae type b or Hib, pneumococcal disease for children and adults, human papillomavirus, varicella, mumps, and hepatitis B). All were cost-effective options, except the Hib and hepatitis B vaccines. Nonetheless, all the vaccines were recommended equally for inclusion in the routine immunization program. While it is significant that policy-makers decided to commission economic assessments at all, various issues remain regarding the influence of external pressure, the choice of evaluation methods and the implications of using cost-effectiveness analyses on the future of Japanese health policy-making. PMID- 25139709 TI - The 3 A's of the access process to long-term care for elderly: providers experiences in a multiple case study in the Netherlands. AB - The access process is an important step in the care provision to independently living elderly. Still, little attention has been given to the process of access to long-term care for older clients. Access can be described by three dimensions: availability, affordability and acceptability (three A's). In this paper we address the following question: How do care providers take the three dimensions of access into account for the access process to their care and related service provision to independently living elderly? To answer this question we performed a qualitative study. We used data gathered in a multiple case study in the Netherlands. This study provides insight in the way long-term care organizations organize their access process. Not all dimensions were equally present or acknowledged by the case organizations. The dimension acceptability seems an important dimension in the access process, as shown by the efforts done in building a relationship with their clients, mainly through a strong personal relationship between client and care advisor. In that respect it is remarkable that the case organizations do not structurally evaluate their access process. Availability is compromised by practical issues and organizational choices. Affordability hardly seems an issue. Further research can reveal the underlying factors that influence the three A dimensions. PMID- 25139710 TI - An immune dysregulation in MPN. AB - Myeloproliferative neoplasms (MPNs) are stem cell-derived clonal myeloid malignancies characterized by a unique somatic mutational profile since three mutually exclusive mutations (JAK2V617F, MPL, and CALR) sustain the great majority of the cases. However, clinical observation that autoimmune diseases may predispose to MPNs, autoimmune disorders or autoimmune phenomena may be associated with MPNs, and genetic constitutional variants that predispose to autoimmune disorders or inflammatory phenomena also predispose to MPNs raises a hypothesis that there might be an autoimmune/inflammatory basis underlying the pathogenesis of MPNs. Recent studies have documented that MPNs are characterized by an abnormal activity of key cells of the immune system, for example, increase in monocyte/macrophage compartment, altered regulatory T cell frequency, expansion of myeloid-derived suppressor cells, and CD4/natural killer cell dysfunction. This review is focused on summarizing recent advances in our understanding of immunological defects in MPNs with accompanying translational implications. PMID- 25139711 TI - ArsC3 from Desulfovibrio alaskensis G20, a cation and sulfate-independent highly efficient arsenate reductase. AB - Desulfovibrio alaskensis G20, a sulfate-reducing bacterium, contains an arsRBC2C3 operon that encodes two putative arsenate reductases, DaG20_ArsC2 and DaG20_ArsC3. In this study, resistance assays in E. coli transformed with plasmids containing either of the two recombinant arsenate reductases, showed that only DaG20_ArsC3 is functional and able to confer arsenate resistance. Kinetic studies revealed that this enzyme uses thioredoxin as electron donor and therefore belongs to Staphylococcus aureus plasmid pI258 and Bacillus subtilis thioredoxin-coupled arsenate reductases family. Both enzymes from this family contain a potassium-binding site, but only in Sa_ArsC does potassium actually binds resulting in a lower K m. Important differences between the S. aureus and B. subtilis enzymes and DaG20_ArsC3 are observed. DaG20_ArsC3 contains only two (Asn10, Ser33) of the four (Asn10, Ser33, Thr63, Asp65) conserved amino acid residues that form the potassium-binding site and the kinetics is not significantly affected by the presence of either potassium or sulfate ions. Isothermal titration calorimetry measurements confirmed nonspecific binding of K(+) and Na(+), corroborating the non-relevance of these cations for catalysis. Furthermore, the low K m and high k cat values determined for DaG20_ArsC3 revealed that this enzyme is the most catalytically efficient potassium independent arsenate reductase described so far and, for the first time indicates that potassium binding is not essential to have low K m, for Trx-arsenate reductases. PMID- 25139712 TI - Trends in U.S. emergency department visits for opioid overdose, 1993-2010. AB - OBJECTIVE: Emergency department (ED) visits for opioid overdose provide an important marker of acute morbidity. We sought to evaluate national trends of ED visits for opioid overdose. DESIGN, SETTING, AND PARTICIPANTS: The National Hospital Ambulatory Medical Care Survey, 1993-2010, was used to identify ED visits for opioid overdose. OUTCOME MEASURES: Outcome measures were national ED visit rates for opioid overdose per 100,000 U.S. population and per 100,000 ED visits. RESULTS: From 1993 to 2010, there were approximately 731,000 ED visits (95% CI, 586,000-877,000 visits) for opioid overdose, representing an overall rate of 14 ED visits (95% CI, 12-17 visits) per 100,000 population and 37 ED visits (95% CI, 31-45 visits) per 100,000 ED visits. Of these, 41% (95% CI, 33 50%) were for prescription opioid overdose. Between 1993 and 2010, the national visit rate increased from 7 to 27 per 100,000 population (+307%; Ptrend = 0.03), and from 19 to 63 per 100,000 ED visits (+235%; Ptrend < 0.001). Stratified analyses of the visit rate per population showed upward, but nonsignificant, trends across multiple demographic groups and U.S. regions. In stratified analyses of the visit rate per 100,000 ED visits, the rate increased significantly in several groups: age <20 years (+1188%; Ptrend = 0.002), age 20 29 years (+155%; Ptrend = 0.04), age >=50 years (+231%; Ptrend = 0.04), female (+234%; Ptrend = 0.001), male (+80%; Ptrend = 0.04), whites (+187%; Ptrend < 0.001), and patients in the South (+371%; Ptrend < 0.001). CONCLUSION: In a nationally representative database of U.S. ED visits, we found that the ED visit rate for opioid overdose quadrupled from 1993 to 2010. Our findings suggest that previous prevention measures may not be adequate. PMID- 25139714 TI - B7-H3 expression in colorectal cancer: associations with clinicopathological parameters and patient outcome. AB - BACKGROUND: We have previously reported overexpression of the immunoregulatory protein B7-H3 in colorectal cancer and that nuclear expression predicted poor outcome in colon cancer patients. The present study was performed to examine the prognostic role of B7-H3 in an independent colorectal cancer cohort. METHODS: Using tissue microarrays from 731 colorectal cancer patients, tumour B7-H3 expression was assessed by immunohistochemistry. Associations with clinicopathological parameters and patient outcome were investigated. RESULTS: Nuclear expression of B7-H3 in cancer cells was present in 27% of the samples in the total study cohort, while cytoplasmic/membrane and stromal expression was seen in 86% and 77% of the samples, respectively. Nuclear B7-H3 had no prognostic relevance in the complete outcome cohort, neither in colon cancer patients. However, nuclear B7-H3 was significantly associated with reduced recurrence-free survival in TNM stage I colorectal cancer patients. CONCLUSIONS: Overexpression of B7-H3 in colorectal cancer was confirmed, but in contrast to previous results, nuclear B7-H3 was not a strong prognostic biomarker in this cohort. The discrepancy might be related to the use of single-core tissue microarrays for detection of the heterogeneously expressed B7-H3, and the role of B7-H3 in colorectal cancer still needs further examination. PMID- 25139715 TI - Influence of wound drainage in primary total knee arthroplasty without tourniquet. AB - PURPOSE: Although it remains the golden standard, several authors have questioned the role of pneumatic tourniquets in primary knee arthroplasty in recent studies. An intra-articular wound drainage is widely used in the field of total knee arthroplasty although the benefit of postoperative wound drainage is controversial in the literature. This study questioned whether the use of an intra-articular drain is an advance over the lack of a drain in total knee arthroplasty which is performed without a tourniquet. METHODS: We documented the ROM, the knee circumference at the upper patellar pole pre-operatively and on days two, four and six postoperatively. The blood volume and loss was calculated. As surrogate parameter for wound healing we counted the number of days until no residual secretion was observed via the wound/drainage site. RESULTS: The results of our investigation showed a significantly better wound healing without the use of a drain. All other parameters revealed no significant differences. CONCLUSION: The data of this study demonstrate a faster wound healing without the use of a postoperative wound drain in primary total knee arthroplasty which is performed without a tourniquet. Other parameters could not show any significant differences thus indicating that a postoperative wound drain has no significant advantage and the risk of a retrograde bacterial colonisation is well documented. Based on these data we recommend performing a primary total knee arthroplasty without a postoperative drain if the procedure is done without a tourniquet. PMID- 25139716 TI - Prospective randomized trial comparing open reduction and internal fixation with minimally invasive reduction and percutaneous fixation in managing displaced intra-articular calcaneal fractures. AB - PURPOSE: Managing displaced intra-articular calcaneal fractures remains controversial. A prospective randomised trial was undertaken to compare open reduction and internal fixation (ORIF) with minimally invasive reduction and percutaneous fixation (MIRPF). METHODS: Forty-five displaced intra-articular calcaneal fractures were randomised to undergo either ORIF (n = 23) or MIRPF (n = 22). Patients were followed up clinically and radiologically for a minimum of one year postoperatively. The primary outcome measure was wound-healing complication. Functional outcome was assessed using Creighton Nebraska Health Foundation (CNF) scale, and radiological outcome was assessed using plain radiographs and computed tomography (CT) scans. RESULTS: Of the 23 heels in the ORIF group, seven (30%) had wound-healing problems, compared with none in the MIRPF group (p = 0.005). There was no statistically significant difference in radiological outcomes between groups, as measured by Bohler's angle, Gissane's angle and Score Analysis of Verona (SAVE). Median time to return to work was two weeks earlier (p = 0.004), and the functional outcome score (CNF scale) at one year of follow-up was better (p = 0.013) following MIRPF compared with ORIF. CONCLUSION: MIRPF is associated with fewer wound-healing problems, better functional outcome and earlier return to work compared with ORIF. PMID- 25139717 TI - Cryoablation, limited fluoroscopy, and more. PMID- 25139718 TI - The significance of oxygen during contact lens wear. AB - In order to establish the relevance of oxygen to contemporary contact lens practice, a review of the literature was conducted. The results indicate that there are a number of processes occurring in the normal healthy eye where oxygen is required and which are potentially affected by the presence of a contact lens. These activities appear to take place at all corneal levels, as well as at the limbus. Evidence from laboratory, clinical and modelling studies indicates that what constitutes normal oxygenation (normoxia) depends on, among other things, the physiological system under consideration, corneal location and the state of eye closure. This diversity is reflected in the wide range of minimum lens oxygen transmissibility (Dk/t) requirements that are present in a literature. PMID- 25139719 TI - Power profiles of single vision and multifocal soft contact lenses. AB - PURPOSE: The purpose of this study was to investigate the optical zone power profile of the most commonly prescribed soft contact lenses to assess their potential impact on peripheral refractive error and hence myopia progression. METHODS: The optical power profiles of six single vision and ten multifocal contact lenses of five manufacturers in the powers -1.00 D, -3.00 D, and -6.00 D were measured using the SHSOphthalmic (Optocraft GmbH, Erlangen, Germany). Instrument repeatability was also investigated. RESULTS: Instrument repeatability was dependent on the distance from the optical centre, manifesting unreliable data for the central 1mm of the optic zone. Single vision contact lens measurements of -6.00 D lenses revealed omafilcon A having the most negative spherical aberration, lotrafilcon A having the least. Somofilcon A had the highest minus power and lotrafilcon A the biggest deviation in positive direction, relative to their respective labelled powers. Negative spherical aberration occurred for almost all of the multifocal contact lenses, including the centre-distance designs etafilcon A bifocal and omafilcon A multifocal. Lotrafilcon B and balafilcon A seem to rely predominantly on the spherical aberration component to provide multifocality. CONCLUSIONS: Power profiles of single vision soft contact lenses varied greatly, many having a negative spherical aberration profile that would exacerbate myopia. Some lens types and powers are affected by large intra-batch variability or power offsets of more than 0.25 dioptres. Evaluation of power profiles of multifocal lenses was derived that provides helpful information for prescribing lenses for presbyopes and progressing myopes. PMID- 25139720 TI - Scoring hip osteoarthritis with MRI (SHOMRI): A whole joint osteoarthritis evaluation system. AB - BACKGROUND: To develop a semi-quantitative MR-based hip osteoarthritis (OA) evaluation system (Scoring hip osteoarthritis with MRI, SHOMRI), and to test its reproducibility and face validity. METHODS: The study involved 98 subjects with informed consent. Three-Tesla MR imaging of hip was performed in three planes with intermediate-weighted fat saturated FSE sequences. Two radiologists assessed cartilage loss, bone marrow edema pattern, subchondral cyst in 10 subregions, and assessed labrum in 4 subregions. In addition, presence or absence of ligamentum teres integrity, paralabral cysts, intra-articular body, and effusion in the hip joint were analyzed using the SHOMRI system. The reproducibility was assessed with intra-class correlation coefficient (ICC), Cohen's Kappa values and percent agreement. SHOMRI scores were correlated with radiographic Kellgren-Lawrence (KL) and OARSI atlas gradings, and clinical parameters, the hip osteoarthritis outcome score (HOOS) and hip range of motion (ROM), using Spearman's rank correlation and ordinal logistic regression. RESULTS: ICC values were in the excellent range, 0.91 to 0.97. Cohen's Kappa values and percent agreement ranged from 0.55 to 0.79 and 66 to 99%, respectively. SHOMRI demonstrated significant correlations with KL and OARSI gradings as well as with clinical parameters, HOOS and ROM (P < 0.05). Among the SHOMRI features, subchondral cyst and bone marrow edema pattern showed the highest correlation with HOOS and ROM. CONCLUSION: SHOMRI demonstrated moderate to excellent reproducibility and significant correlation with radiographic gradings and clinical parameters. PMID- 25139721 TI - Authors' reply to de Vries. PMID- 25139722 TI - Male-specific use of the purr in the ring-tailed lemur (Lemur catta). AB - In mammals, purring has been described in mostly affiliative contexts. In the ring-tailed lemur (Lemur catta), both males and females purr, but only males were observed purring in agonistic contexts. In order to determine whether male ring tailed lemurs purr as aggressive displays during intrasexual agonistic encounters, 480 h of focal data were collected on 25 adult males from Beza Mahafaly Special Reserve, Madagascar, from March to July 2010. The male purring rate increased during periods of male-male agonism when compared to times without intrasexual agonism, and the purring rate was positively correlated with male dominance rank. However, the purring rate was not significantly higher during winning agonistic interactions when compared with losing encounters. My results indicate that the male ring-tailed lemur purr is used most frequently as an agonistic vocalization in male-male encounters, in addition to being used less frequently in other social contexts, including during tail-waving at females, resting, scent-marking, feeding and copulation. Dominant males have higher purring rates across social situations, suggesting that the purring rate may be driven by intrinsic male qualities rather than functioning as a meaningful signal in each disparate social context. Male purring in intrasexual agonistic encounters can be added to previously described social contexts for ring-tailed lemur purring. PMID- 25139723 TI - Patient and provider perspectives on Bedsider.org, an online contraceptive information tool, in a low income, racially diverse clinic population. AB - OBJECTIVE: To explore patient and provider perspectives regarding a new Web-based contraceptive support tool. STUDY DESIGN: We conducted a qualitative study at an urban Medicaid-based clinic among sexually active women interested in starting a new contraceptive method, clinic providers and staff. All participants were given the opportunity to explore Bedsider, an online contraceptive support tool developed for sexually active women ages 18-29 by the National Campaign to Prevent Teen and Unplanned Pregnancy and endorsed by the American Congress of Obstetricians and Gynecologists. Focus groups were conducted separately among patient participants and clinic providers/staff using open-ended structured interview guides to identify specific themes and key concepts related to use of this tool in an urban clinic setting. RESULTS: Patient participants were very receptive to this online contraceptive support tool, describing it as trustworthy, accessible and empowering. In contrast, clinic providers and staff had concerns regarding the Website's legitimacy, accessibility, ability to empower patients and applicability, which limited their willingness to recommend its use to patients. CONCLUSION: Contrasting opinions regarding Bedsider may point to a potential disconnect between how providers and patients view contraception information tools. Further qualitative and quantitative studies are needed to explore women's perspectives on contraceptive education and counseling and providers' understanding of these perspectives. IMPLICATIONS STATEMENT: This study identifies a contrast between how patients and providers in an urban clinic setting perceive a Web-based contraceptive tool. Given a potential patient provider discrepancy in preferred methods and approaches to contraceptive counseling, additional research is needed to enhance this important arena of women's health care. PMID- 25139724 TI - Intrauterine lidocaine for pain control during laminaria insertion: a randomized controlled trial. AB - OBJECTIVE: To determine if intrauterine administration of 5 cc of 2% lidocaine in addition to paracervical block reduces pain during laminaria insertion, when compared with paracervical block and saline placebo. STUDY DESIGN: This was a randomized, double blind placebo-controlled trial. Women presenting for abortion by dilation and evacuation (D&E) at 14-24 weeks gestational age were randomized to receive an intrauterine instillation of either 5 mL of 2% lidocaine or 5 mL of normal saline, in addition to standard paracervical block with 20 cc of 0.25% bupivacaine. Our primary outcome was self-reported pain scores on a 100mm Visual Analogue Scale (VAS) immediately following laminaria insertion. Secondary outcome was self-reported VAS pain score indicating the maximum level of pain experienced during the 24-48-h interval between laminaria insertion and D&E procedure. RESULTS: Seventy-two women were enrolled, and data for 67 women were analyzed, only two of whom were more than 21 weeks on gestation. The range of pain scores at both time points was large (1-90 mm at laminaria insertion; 0-100mm in laminaria-D&E interval). Mean pain scores were not different between treatment groups at laminaria insertion, (33 vs. 32, p=.8) or in the laminaria - D&E interval (43 vs. 44, p=.9). CONCLUSION: Intrauterine administration of 5 cc of 2% lidocaine in addition to paracervical block did not reduce pain with laminaria insertion when compared to paracervical block with saline placebo. IMPLICATIONS: Intrauterine lidocaine combined with paracervical block does not improve pain control at laminaria insertion when compared with paracervical block and saline placebo. Wide variation in pain scores and persistent pain after laminaria insertion suggests patient would benefit from more effective methods of pain control at laminaria insertion and during the post-laminaria interval. PMID- 25139725 TI - Recent advances in the structure-based and ligand-based design of IKKbeta inhibitors as anti-inflammation and anti-cancer agents. AB - NF-kappaB is a significant transcription factor that regulates the expression of various pro-survival genes. IKK is a crucial protein kinase that activates NF kappaB translocating from cytoplasm to nucleus for DNA binding. It is composed of three subunits, IKKalpha, IKKbeta, IKKgamma (NEMO), where IKKalpha and IKKbeta are catalytic subunits, and IKKgamma is the regulatory subunit. Many diseases, such as Hodgkin's disease, Hepatitis-associated hepatocellular carcinoma, colorectal cancer, prostate cancer, rheumatoid arthritis and inflammatory bowel disease, are related to IKK and NF-kappaB. So far, various IKK inhibitors targeting the ATP binding site have been identified through high throughput screening, rational design or in silico methods, however, only three of them (CHS 828, EB-1627 and IMD-1041) have been under clinical studies, indicating the strategy for the design of IKK inhibitors need to be reinspected. Besides ATP competitive inhibitors, several other inhibitors have also been disclosed recently, which provide novel concepts to the discovery of IKK inhibitors. In this review, we focus on two parts: 1) the chemotypes and binding patterns of the traditional ATP-competitive IKK inhibitors; 2) novel strategies for the identification of non-ATP-competitive IKK inhibitors as NF-kappaB modulators. Through these discussions we hope to present inspirations for the development of new IKK inhibitors. PMID- 25139727 TI - Mindfulness-based intervention to treat insomnia in elderly people. PMID- 25139726 TI - Rationale and design of REWARD (revving-up exercise for sustained weight loss by altering neurological reward and drive): a randomized trial in obese endometrial cancer survivors. AB - BACKGROUND: Obesity is a leading risk factor for endometrial cancer (EC), particularly Type I forms, which are increasing in the U.S. Although death rates from most cancers have been decreasing, overall mortality in EC is increasing in the U.S. EC survivors' poor fitness combined with their surgical treatments may make weight loss particularly challenging. High intensity exercise increases neurotrophins and neurological reward via altered striatal dopamine in animals, and, in humans, chronic high intensity exercise enhances meal-induced satiety and may reduce hedonic eating. "Assisted" exercise, a mode of exercise whereby a patient's voluntary exercise rate is augmented mechanically, may modulate brain dopamine levels in Parkinson's Disease patients but has not been previously evaluated as a treatment for obesity. METHODS: We describe the rationale and design of the REWARD trial, which has the overarching goal of randomizing 120 obese EC survivors to "assisted" or voluntary rate cycling to evaluate the efficacy of "assisted" exercise in enhancing and sustaining weight loss. Patients in both arms will receive 3 days/week of supervised exercise and 1 day/week of a group dietary behavioral intervention for 16 weeks and, then, will be followed for 6 months. OUTCOMES: The primary outcome is weight loss. Secondary outcomes include measures for body composition, fitness, eating behavior, exercise motivation and, quality of life as well as cognition and food reward and motivation as assessed by functional magnetic resonance imaging (fMRI) tasks. CONCLUSIONS: If successful, the REWARD program could be extended to help sustain weight loss in obese cancer and non-cancer patients. PMID- 25139728 TI - Enhancing physical and social environments to reduce obesity among public housing residents: rationale, trial design, and baseline data for the Healthy Families study. AB - Intervention programs that change environments have the potential for greater population impact on obesity compared to individual-level programs. We began a cluster randomized, multi-component multi-level intervention to improve weight, diet, and physical activity among low-socioeconomic status public housing residents. Here we describe the rationale, intervention design, and baseline survey data. After approaching 12 developments, ten were randomized to intervention (n=5) or assessment-only control (n=5). All residents in intervention developments are welcome to attend any intervention component: health screenings, mobile food bus, walking groups, cooking demonstrations, and a social media campaign; all of which are facilitated by community health workers who are residents trained in health outreach. To evaluate weight and behavioral outcomes, a subgroup of female residents and their daughters age 8-15 were recruited into an evaluation cohort. In total, 211 households completed the survey (RR=46.44%). Respondents were Latino (63%), Black (24%), and had <= high school education (64%). Respondents reported <=2 servings of fruits & vegetables/day (62%), visiting fast food restaurants 1+ times/week (32%), and drinking soft drinks daily or more (27%). The only difference between randomized groups was race/ethnicity, with more Black residents in the intervention vs. control group (28% vs. 19%, p=0.0146). Among low-socioeconomic status urban public housing residents, we successfully recruited and randomized families into a multi-level intervention targeting obesity. If successful, this intervention model could be adopted in other public housing developments or entities that also employ community health workers, such as food assistance programs or hospitals. PMID- 25139729 TI - Survival benefit of primary deceased donor transplantation with high-KDPI kidneys. AB - The Kidney Donor Profile Index (KDPI) has been introduced as an aid to evaluating deceased donor kidney offers, but the relative benefit of high-KDPI kidney transplantation (KT) versus the clinical alternative (remaining on the waitlist until receipt of a lower KDPI kidney) remains unknown. Using time-dependent Cox regression, we evaluated the mortality risk associated with high-KDPI KT (KDPI 71 80, 81-90 or 91-100) versus a conservative, lower KDPI approach (remain on waitlist until receipt of KT with KDPI 0-70, 0-80 or 0-90) in first-time adult registrants, adjusting for candidate characteristics. High-KDPI KT was associated with increased short-term but decreased long-term mortality risk. Recipients of KDPI 71-80 KT, KDPI 81-90 KT and KDPI 91-100 KT reached a "break-even point" of cumulative survival at 7.7, 18.0 and 19.8 months post-KT, respectively, and had a survival benefit thereafter. Cumulative survival at 5 years was better in all three high-KDPI groups than the conservative approach (p < 0.01 for each comparison). Benefit of high-KDPI KT was greatest in patients age >50 years and patients at centers with median wait time >=33 months. Recipients of high-KDPI KT can enjoy better long-term survival; a high-KDPI score does not automatically constitute a reason to reject a deceased donor kidney. PMID- 25139730 TI - Effects of ranibizumab on the extracellular matrix production by human Tenon's fibroblast. AB - Anti-Vascular Endothelial Growth Factors (Anti-VEGF) agents have received recent interest as potential anti-fibrotic agents for their concurrent use with trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology following trabeculectomy augmented with ranibizumab. The effects of this humanized monoclonal antibody on human Tenon's fibroblast (HTF), the key player of post trabeculectomy scar formation, are not fully understood. This study was conducted to understand the effects of ranibizumab on extracellular matrix production by HTF. The effect of ranibizumab on HTF proliferation and cell viability was determined using MTT assay (3-(4,5-dimethylthiazone-2-yl)-2,5 diphenyl tetrazolium). Ranibizumab at concentrations ranging from 0.01 to 0.5 mg/mL were administered for 24, 48 and 72 h in serum and serum free conditions. Supernatants and cell lysates from samples were assessed for collagen type 1 alpha 1 and fibronectin mRNA and protein level using quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). After 48-h, ranibizumab at 0.5 mg/mL, significantly induced cell death under serum-free culture conditions (p < 0.05). Ranibizumab caused significant reduction of collagen type 1 alpha 1 (COL1A1) mRNA, but not for fibronectin (FN). Meanwhile, COL1A1 and FN protein levels were found upregulated in treated monolayers compared to control monolayers. Ranibizumab at 0.5 mg/mL significantly reduced cell viability in cultured HTF. From this study, we found that single application of ranibizumab is inadequate to induce the anti-fibrotic effects on HTF, suggesting the importance of adjunctive therapy. Further studies are underway to understand mechanism of actions of ranibizumab on HTF. PMID- 25139731 TI - Observation of interstitial molecular hydrogen in clathrate hydrates. AB - The current knowledge and description of guest molecules within clathrate hydrates only accounts for occupancy within regular polyhedral water cages. Experimental measurements and simulations, examining the tert-butylamine + H2 + H2O hydrate system, now suggest that H2 can also be incorporated within hydrate crystal structures by occupying interstitial sites, that is, locations other than the interior of regular polyhedral water cages. Specifically, H2 is found within the shared heptagonal faces of the large (4(3)5(9)6(2)7(3)) cage and in cavities formed from the disruption of smaller (4(4)5(4)) water cages. The ability of H2 to occupy these interstitial sites and fluctuate position in the crystal lattice demonstrates the dynamic behavior of H2 in solids and reveals new insight into guest-guest and guest-host interactions in clathrate hydrates, with potential implications in increasing overall energy storage properties. PMID- 25139732 TI - Hyperosmolar tears enhance cooling sensitivity of the corneal nerves in rats: possible neural basis for cold-induced dry eye pain. AB - PURPOSE: Tear hyperosmolarity is a ubiquitous feature of dry-eye disease. Although dry-eye patients' sensitivity to cooling is well known, the effects of tear hyperosmolarity on a small amount of cooling in the corneal nerves have not been quantitatively examined. Recently reported corneal afferents, high-threshold cold sensitive plus dry-sensitive (HT-CS + DS) neurons, in rats is normally excited by strong (>4 degrees C) cooling of the cornea, which, when applied to healthy humans, evokes the sensation of discomfort. However, corneal cooling measured between blinks does not exceed 2 degrees C normally. Thus, we sought to determine if these nociceptors could be sensitized by hyperosmolar tears such that they are now activated by small cooling of the ocular surface. METHODS: Trigeminal ganglion neurons innervating the cornea were extracellularly recorded in isoflurane-anesthetized rats. The responses of single corneal neurons to cooling stimuli presented in the presence of hyperosmolar (350-800 mOsm NaCl) tears were examined. RESULTS: The HT-CS + DS neurons with thresholds averaging 4 degrees C cooling responded to cooling stimuli presented after 15 minutes of hyperosmolar tears with thresholds of less than 1 degrees C. The response magnitudes also were enhanced so that the responses to small (2 degrees C) cooling emerged, where none was observed before. CONCLUSIONS: These results demonstrate that after exposure to hyperosmolar tears, these nociceptive corneal neurons now begin to respond to the slight cooling normally encountered between blinks, enabling the painful information to be carried to the brain, which could explain the cooling-evoked discomfort in dry eye patients. PMID- 25139733 TI - NF-kappaB-mediated nitric oxide production and activation of caspase-3 cause retinal ganglion cell death in the hypoxic neonatal retina. AB - PURPOSE: Hypoxic insult to the developing retina results in apoptosis of retinal ganglion cells (RGCs) through production of inflammatory mediators, nitric oxide (NO), and free radicals. The present study was aimed at elucidating the pathway through which hypoxia results in overproduction of NO in the immature retina, and its role in causing apoptosis of RGCs. METHODS: Wistar rats (1 day old) were exposed to hypoxia and their retinas were studied at 3 hours to 14 days after exposure. The protein expression of nuclear factor-kappaB (NF-kappaB) and neuronal nitric oxide synthase (nNOS) in the retina and primary cultures of RGCs was analyzed using Western blotting and double-immunofluorescence, whereas the concentration of NO was determined calorimetrically. In cultured RGCs, hypoxia induced apoptosis was evaluated by caspase-3 immunolabeling. RESULTS: Following hypoxic exposure, NF-kappaB-mediated expression of nNOS, which was localized to the RGCs, and subsequent NO production was significantly increased in the developing retina. In primary cultures of RGCs subjected to hypoxia, the upregulation of nNOS and NO was significantly suppressed when treated with 7 nitroindazole (7-NINA), an nNOS inhibitor or BAY, an NF-kappaB inhibitor. Hypoxia induced apoptosis of RGCs, which was evident with caspase-3 labeling, also was suppressed when these cells were treated with 7-NINA or BAY. CONCLUSIONS: Our results suggest that in RGCs, hypoxic induction of nNOS is mediated by NF-kappaB and the resulting increased release of NO by RGCs causes their apoptosis through caspase-3 activation. It is speculated that targeting nNOS could be a potential neuroprotective strategy against hypoxia-induced RGCs death in the developing retina. PMID- 25139734 TI - Mesothelial cells: a cellular surrogate for tissue engineering of corneal endothelium. AB - PURPOSE: To evaluate whether mouse adipose tissue mesothelial cells (ATMCs) share morphologic and biochemical characteristics with mouse corneal endothelial cells (CECs) and to evaluate their capacity to adhere to the decellularized basal membrane of human anterior lens capsules (HALCs) as a potential tissue-engineered surrogate for corneal endothelium replacement. METHODS: Adipose tissue mesothelial cells were isolated from the visceral adipose tissue of adult mice, and their expression of several corneal endothelium markers was determined with quantitative RT-PCR, immunofluorescence, and Western blotting. Adipose tissue mesothelial cells were cultured in a mesothelial retaining phenotype medium (MRPM) and further seeded and cultured on top of the decellularized basal membrane of HALCs. ATMC-HALC composites were evaluated by optical microscopy, immunofluorescence, and transmission electron microscopy. RESULTS: Mesothelial retaining phenotype medium-cultured ATMCs express the corneal endothelium markers COL4A2, COL8A2, SLC4A4, CAR2, sodium- and potassium-dependent adenosine triphosphatase (Na(+)/K(+)-ATPase), beta-catenin, zona occludens-1, and N cadherin in a pattern similar to that in mouse CECs. Furthermore, ATMCs displayed strong adhesion capacity onto the basal membrane of HALCs and formed a confluent monolayer within 72 hours of culture in MRPM. Ultrastructural morphologic and marker characteristics displayed by ATMC monolayer on HALCs clearly indicated that ATMCs retained their original phenotype of squamous epithelial-like cells. CONCLUSIONS: Corneal endothelial cells and ATMCs share morphologic (structural) and marker (functional) similarities [corrected]. The ATMCs adhered and formed structures mimicking focal adhesion complexes with the HALC basal membrane. Monolayer structure and achieved density of ATMCs support the proposal to use adult human mesothelial cells (MCs) as a possible surrogate for damaged corneal endothelium. PMID- 25139735 TI - The external limiting membrane in early-onset Stargardt disease. AB - PURPOSE: To describe pathologic changes of the external limiting membrane (ELM) in young patients with early-onset Stargardt (STGD1) disease. METHODS: Twenty-six STGD1 patients aged younger than 20 years with confirmed disease-causing adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) alleles and 30 age-matched unaffected individuals were studied. Spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (AF), and color fundus photography (CFP) images, as well as full-field electroretinograms were obtained and analyzed for one to four visits in each patient. RESULTS: The ELM in all patients exhibited a distinct thickening that was not observed in unaffected individuals. In addition, accumulations of reflective deposits were noted in the outer nuclear layer in every patient. Four patients exhibited a concave protuberance or bulging of a thickened and hyperreflective ELM band within the fovea containing preserved photoreceptors. Longitudinal SD-OCT data in several patients revealed the persistence of this ELM abnormality over a period of time (1-4 years). Furthermore, the edges of the inner segment ellipsoid band appeared to recede earlier than the ELM band in active lesions. CONCLUSIONS: Structural changes seen in the ELM of this cohort may reflect a gliotic response to cellular stress at the photoreceptor level in early-onset STGD1. PMID- 25139736 TI - Anatomic changes in Schlemm's canal and collector channels in normal and primary open-angle glaucoma eyes using low and high perfusion pressures. AB - PURPOSE: To examine the anatomy of Schlemm's canal (SC) and collector channels (CCs) in normal human and primary open-angle glaucoma (POAG) eyes under low and high perfusion pressure. METHODS: In normal (n = 3) and POAG (n = 3) eye pairs, one eye was perfused at 10 mm Hg while the fellow eye was perfused at 20 mm Hg for 2 hours. Eyes were perfusion fixed at like pressures, dissected into quadrants, embedded in Epon Araldite, and scanned by three-dimensional micro computed tomography (3D micro-CT). Schlemm's canal volume, CC orifice area, diameter, and number were measured using ANALYZE software. RESULTS: Normal eyes showed a larger SC volume (3.3-fold) and CC orifice area (9962.8 vs. 8825.2 MUm(2)) and a similar CC diameter (34.3 +/- 17.8 vs. 32.7 +/- 13.0 MUm) at 10 mm Hg compared to 20 mm Hg. In POAG eyes, SC volume (2.0-fold), CC orifice area (8049.2 MUm(2)-6468.4 MUm(2)), and CC diameter (36.2 +/- 19.1 vs. 29.0 +/- 13.8 MUm) were increased in 10 mm Hg compared to 20 mm Hg perfusion pressures. Partial and total CC occlusions were present in normal and POAG eyes, with a 3.7-fold increase in total occlusions in POAG eyes compared to normal eyes at 20 mm Hg. Visualization of CCs increased by 24% in normal and by 21% in POAG eyes at 20 mm Hg compared to 10 mm Hg. Schlemm's canal volume, CC area, and CC diameter were decreased in POAG eyes compared to normal eyes at like pressures. CONCLUSIONS: Compensatory mechanisms for transient and short periods of increased pressure appear to be diminished in POAG eyes. Variable response to pressure change in SC and CCs may be a contributing factor to outflow facility change in POAG eyes. PMID- 25139737 TI - CCR7 is critical for the induction and maintenance of Th17 immunity in dry eye disease. AB - PURPOSE: We characterized antigen-presenting cell (APC)-relevant chemokine receptor expression in dry eye disease (DED), and investigated the effect of topical CC chemokine receptor (CCR)-7 blockade specifically on Th17 cell immunity and dry eye disease severity. METHODS: We induced DED in female C57BL/6 mice. Chemokine receptor expression by corneal APCs was characterized using immunohistochemistry. To determine the functional role of CCR7 in DED, mice were treated topically with either anti-CCR7, a control isotype antibody, or left untreated, and clinical disease severity, Th17 responses, and molecular markers of DED were quantified. RESULTS: Frequencies of CD11b(+) cells and their chemokine expression were increased in the cornea of DED mice. Mice treated topically with anti-CCR7 antibody displayed a significant reduction in clinical disease severity and Th17 response compared to the isotype and untreated groups. Topical CCR7 blockade was effective in ameliorating DED in its acute and chronic stages. CONCLUSIONS: Our findings suggest that CCR7-mediated trafficking of APCs drives the induction and maintenance of Th17 immunity in DED and that CCR7 blockade is effective in suppressing the immunopathogenic mechanisms in DED. PMID- 25139738 TI - HE3286 reduces axonal loss and preserves retinal ganglion cell function in experimental optic neuritis. AB - PURPOSE: Optic nerve inflammation, demyelination, and axonal loss are all prominent features of optic neuritis. While corticosteroids hasten visual recovery in optic neuritis, no treatment improves final visual outcomes. HE3286 (17alpha-ethynyl-5-androstene-3beta,7beta,17beta-triol), a synthetic derivative of a natural steroid, beta-AET (5-androstene-3beta,7beta,17beta-triol), exerts anti-inflammatory effects in several disease models and has purported neuroprotective effects as well. HE3286's ability to suppress optic neuritis was examined in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. METHODS: Experimental autoimmune encephalomyelitis was induced in C57/BL6 mice. Mice were treated daily with intraperitoneal vehicle or 40 mg/kg HE3286. Visual function was assessed by optokinetic responses (OKR) at baseline and every 10 days until euthanasia at 40 days post immunization. Retinas and optic nerves were isolated. Inflammation (hematoxylin and eosin and Iba1 staining), demyelination (Luxol fast blue staining), and axonal loss (neurofilament staining) were assessed in optic nerve sections. Retinal ganglion cells (RGCs) were immunolabeled with Brn3a antibodies to quantify RGC survival. RESULTS: Progressive decreases in OKR occurred in vehicle-treated EAE mice, and HE3286 treatment reduced the level of this vision loss. HE3286 also attenuated the degree of inflammation, demyelination, and axonal loss in EAE optic nerves as compared to nerves from vehicle-treated EAE mice. Retinal ganglion cell loss that occurred in both vehicle- and HE3286-treated EAE mice was reduced in the temporal retinal quadrant of HE3286-treated mice. CONCLUSIONS: HE3286 suppresses inflammation, reduces demyelination and axonal loss, and promotes RGC survival during experimental optic neuritis. Importantly, HE3286 treatment also preserves some RGC function. Results suggest that HE3286 is a potential novel treatment for optic neuritis. PMID- 25139740 TI - A Phase IB multicentre dose-determination study of BHQ880 in combination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events. AB - Dickkopf-1 (DKK1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease in multiple myeloma. BHQ880, a human neutralizing IgG1 anti-DKK1 monoclonal antibody, is being investigated for its impact on multiple myeloma-related bone disease and as an agent with potential anti-myeloma activity. The primary objectives of this Phase IB study were to determine the maximum tolerated dose (MTD) of BHQ880 and to characterize the dose limiting toxicity (DLT) of escalating doses in combination with anti-myeloma therapy and zoledronic acid. Twenty-eight patients were enrolled and received BHQ880 at doses of 3-40 mg/kg. No DLTs were reported, therefore, the MTD was not determined. The recommended Phase II dose was declared as 10 mg/kg, based mainly on saturation data. There was a general trend towards increased bone mineral density (BMD) observed over time; specific increases in spine BMD from Cycle 12 onwards irrespective of new skeletal-related events on study were observed, and increases in bone strength at the spine and hip were also demonstrated in some patients. BHQ880 in combination with zoledronic acid and anti-myeloma therapy was well tolerated and demonstrated potential clinical activity in patients with relapsed or refractory multiple myeloma. PMID- 25139739 TI - Effects of negative stressors on DNA methylation in the brain: implications for mood and anxiety disorders. AB - Stress is a major contributor to anxiety and mood disorders. The recent discovery of epigenetic changes in the brain resulting from stress has enhanced our understanding of the mechanism by which stress is able to promote these disorders. Although epigenetics encompasses chemical modifications that occur at both DNA and histones, much attention has been focused on stress-induced DNA methylation changes on behavior. Here, we review the effect of stress-induced DNA methylation changes on physiological mechanisms that govern behavior and cognition, dysregulation of which can be harmful to mental health. A literature review was performed in the areas of DNA methylation, stress, and their impact on the brain and psychiatric illness. Key findings center on genes involved in the hypothalamic-pituitary-adrenal axis, neurotransmission and neuroplasticity. Using animal models of different stress paradigms and clinical studies, we detail how DNA methylation changes to these genes can alter physiological mechanisms that influence behavior. Appropriate levels of gene expression in the brain play an important role in mental health. This dynamic control can be disrupted by stress induced changes to DNA methylation patterns. Advancement in other areas of epigenetics, such as histone modifications and the discovery of the novel DNA epigenetic mark, 5-hydroxymethylcytosine, could provide additional avenues to consider when determining the epigenetic effects of stress on the brain. PMID- 25139741 TI - Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of IKs, but preserved cAMP-dependent up-regulation. AB - AIMS: Mutations in KCNQ1, encoding for Kv7.1, the alpha-subunit of the IKs channel, cause long-QT syndrome type 1, potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular, during elevated sympathetic tone. Here, we aim at characterizing the p.Lys557Glu (K557E) Kv7.1 mutation, identified in a Dutch kindred, at baseline and during (mimicked) increased adrenergic tone. METHODS AND RESULTS: K557E carriers had moderate QTc prolongation that augmented significantly during exercise. IKs characteristics were determined after co-expressing Kv7.1-wild-type (WT) and/or K557E with minK and Yotiao in Chinese hamster ovary cells. K557E caused IKs loss of function with slowing of the activation kinetics, acceleration of deactivation kinetics, and a rightward shift of voltage-dependent activation. Together, these contributed to a dominant-negative reduction in IKs density. Confocal microscopy and western blot indicated that trafficking of K557E channels was not impaired. Stimulation of WT IKs by 3'-5'-cyclic adenosine monophosphate (cAMP) generated strong current up regulation that was preserved for K557E in both hetero- and homozygosis. Accumulation of IKs at fast rates occurred both in WT and in K557E, but was blunted in the latter. In a computational model, K557E showed a loss of action potential shortening during beta-adrenergic stimulation, in accordance with the lack of QT shortening during exercise in patients. CONCLUSION: K557E causes IKs loss of function with reduced fast rate-dependent current accumulation. cAMP dependent stimulation of mutant IKs is preserved, but incapable of fully compensating for the baseline current reduction, explaining the long QT intervals at baseline and the abnormal QT accommodation during exercise in affected patients. PMID- 25139742 TI - Super-resolution imaging reveals that loss of the C-terminus of connexin43 limits microtubule plus-end capture and NaV1.5 localization at the intercalated disc. AB - AIMS: It is well known that connexin43 (Cx43) forms gap junctions. We recently showed that Cx43 is also part of a protein-interacting network that regulates excitability. Cardiac-specific truncation of Cx43 C-terminus (mutant 'Cx43D378stop') led to lethal arrhythmias. Cx43D378stop localized to the intercalated disc (ID); cell-cell coupling was normal, but there was significant sodium current (INa) loss. We proposed that the microtubule plus-end is at the crux of the Cx43-INa relation. Yet, specific localization of relevant molecular players was prevented due to the resolution limit of fluorescence microscopy. Here, we use nanoscale imaging to establish: (i) the morphology of clusters formed by the microtubule plus-end tracking protein 'end-binding 1' (EB1), (ii) their position, and that of sodium channel alpha-subunit NaV1.5, relative to N cadherin-rich sites, and (iii) the role of Cx43 C-terminus on the above-mentioned parameters and on the location-specific function of INa. METHODS AND RESULTS: Super-resolution fluorescence localization microscopy in murine adult cardiomyocytes revealed EB1 and NaV1.5 as distinct clusters preferentially localized to N-cadherin-rich sites. Extent of co-localization decreased in Cx43D378stop cells. Macropatch and scanning patch clamp showed reduced INa exclusively at cell end, without changes in unitary conductance. Experiments in Cx43-modified HL1 cells confirmed the relation between Cx43, INa, and microtubules. CONCLUSIONS: NaV1.5 and EB1 localization at the cell end is Cx43 dependent. Cx43 is part of a molecular complex that determines capture of the microtubule plus-end at the ID, facilitating cargo delivery. These observations link excitability and electrical coupling through a common molecular mechanism. PMID- 25139743 TI - Glyoxalase 1 overexpression does not affect atherosclerotic lesion size and severity in ApoE-/- mice with or without diabetes. AB - AIMS: Advanced glycation end-products (AGEs) and their precursors have been associated with the development of atherosclerosis. We recently discovered that glyoxalase 1 (GLO1), the major detoxifying enzyme for AGE precursors, is decreased in ruptured human plaques, and that levels of AGEs are higher in rupture-prone plaques. We here investigated whether overexpression of human GLO1 in ApoE(-/-) mice could reduce the development of atherosclerosis. METHODS AND RESULTS: We crossed C57BL/6 ApoE(-/-) mice with C57BL/6 GLO1 overexpressing mice (huGLO1(+/-)) to generate ApoE(-/-) (n = 16) and ApoE(-/-) huGLO1(+/-) (n = 20) mice. To induce diabetes, we injected a subset with streptozotocin (STZ) to generate diabetic ApoE(-/-) (n = 8) and ApoE(-/-) huGLO1(+/-) (n = 13) mice. All mice were fed chow and sacrificed at 25 weeks of age. The GLO1 activity was three fold increased in huGLO1(+/-) aorta, but aortic root lesion size and phenotype did not differ between mice with and without huGLO1(+/-) overexpression. We detected no differences in gene expression in aortic arches, in AGE levels and cytokines, in circulating cells, and endothelial function between ApoE(-/-) mice with and without huGLO1(+/-) overexpression. Although diabetic mice showed decreased GLO1 expression (P < 0.05) and increased lesion size (P < 0.05) in comparison with non-diabetic mice, GLO1 overexpression also did not affect the aortic root lesion size or inflammation in diabetic mice. CONCLUSION: In ApoE(-/ ) mice with or without diabetes, GLO1 overexpression did not lead to decreased atherosclerotic lesion size or systemic inflammation. Increasing GLO1 levels does not seem to be an effective strategy to reduce glycation in atherosclerotic lesions, likely due to increased AGE formation through GLO1-independent mechanisms. PMID- 25139744 TI - The cellular prion protein counteracts cardiac oxidative stress. AB - AIMS: The cellular prion protein, PrP(C), whose aberrant isoforms are related to prion diseases of humans and animals, has a still obscure physiological function. Having observed an increased expression of PrP(C) in two in vivo paradigms of heart remodelling, we focused on isolated mouse hearts to ascertain the capacity of PrP(C) to antagonize oxidative damage induced by ischaemic and non-ischaemic protocols. METHODS AND RESULTS: Hearts isolated from mice expressing PrP(C) in variable amounts were subjected to different and complementary oxidative perfusion protocols. Accumulation of reactive oxygen species, oxidation of myofibrillar proteins, and cell death were evaluated. We found that overexpressed PrP(C) reduced oxidative stress and cell death caused by post-ischaemic reperfusion. Conversely, deletion of PrP(C) increased oxidative stress during both ischaemic preconditioning and perfusion (15 min) with H2O2. Supporting its relation with intracellular systems involved in oxidative stress, PrP(C) was found to influence the activity of catalase and, for the first time, the expression of p66(Shc), a protein implicated in oxidative stress-mediated cell death. CONCLUSIONS: Our data demonstrate that PrP(C) contributes to the cardiac mechanisms antagonizing oxidative insults. PMID- 25139745 TI - Scrib:Rac1 interactions are required for the morphogenesis of the ventricular myocardium. AB - AIMS: The organization and maturation of ventricular cardiomyocytes from the embryonic to the adult form is crucial for normal cardiac function. We have shown that a polarity protein, Scrib, may be involved in regulating the early stages of this process. Our goal was to establish whether Scrib plays a cell autonomous role in the ventricular myocardium, and whether this involves well-known polarity pathways. METHODS AND RESULTS: Deletion of Scrib in cardiac precursors utilizing Scrib(flox) mice together with the Nkx2.5-Cre driver resulted in disruption of the cytoarchitecture of the forming trabeculae and ventricular septal defects. Although the majority of mice lacking Scrib in the myocardium survived to adulthood, they developed marked cardiac fibrosis. Scrib did not physically interact with the planar cell polarity (PCP) protein, Vangl2, in early cardiomyocytes as it does in other tissues, suggesting that the anomalies did not result from disruption of PCP signalling. However, Scrib interacted with Rac1 physically in embryonic cardiomyocytes and genetically to result in ventricular abnormalities, suggesting that this interaction is crucial for the development of the early myocardium. CONCLUSIONS: The Scrib-Rac1 interaction plays a crucial role in the organization of developing cardiomyocytes and formation of the ventricular myocardium. Thus, we have identified a novel signalling pathway in the early, functioning, heart muscle. These data also show that the foetus can recover from relatively severe abnormalities in prenatal ventricular development, although cardiac fibrosis can be a long-term consequence. PMID- 25139746 TI - Nitric oxide and protein kinase G act on TRPC1 to inhibit 11,12-EET-induced vascular relaxation. AB - AIMS: Vascular endothelial cells synthesize and release vasodilators such as nitric oxide (NO) and epoxyeicosatrienoic acids (EETs). NO is known to inhibit EET-induced smooth muscle hyperpolarization and relaxation. This study investigates the underlying mechanism of this inhibition. METHODS AND RESULTS: Through measurements of membrane potential and arterial tension, we show that 11,12-EET induced membrane hyperpolarization and vascular relaxation in endothelium-denuded porcine coronary arteries. These responses were suppressed by S-nitroso-N-acetylpenicillamine (SNAP) and 8-Br-cGMP, an NO donor and a membrane permeant analogue of cGMP, respectively. The inhibitory actions of SNAP and 8-Br cGMP on 11,12-EET-induced membrane hyperpolarization and vascular relaxation were reversed by hydroxocobalamin, an NO scavenger; ODQ, a guanylyl cyclase inhibitor; and KT5823, a protein kinase G (PKG) inhibitor. The inhibitory actions of SNAP and 8-bromo cyclic GMP (8-Br-cGMP) on the EET responses were also abrogated by shielding TRPC1-PKG phosphorylation sites with an excessive supply of exogenous PKG substrates, TAT-TRPC1(S172) and TAT-TRPC1(T313). Furthermore, a phosphorylation assay demonstrated that PKG could directly phosphorylate TRPC1 at Ser(172) and Thr(313). In addition, 11,12-EET failed to induce membrane hyperpolarization and vascular relaxation when TRPV4, TRPC1, or KCa1.1 was selectively inhibited. Co-immunoprecipitation studies demonstrated that TRPV4, TRPC1, and KCa1.1 physically associated with each other in smooth muscle cells. CONCLUSION: Our findings demonstrate a novel role of the NO-cGMP-PKG pathway in the inhibition of 11,12-EET-induced smooth muscle hyperpolarization and relaxation via PKG-mediated phosphorylation of TRPC1. PMID- 25139747 TI - Ranolazine prevents INaL enhancement and blunts myocardial remodelling in a model of pulmonary hypertension. AB - AIMS: Pulmonary arterial hypertension (PAH) reflects abnormal pulmonary vascular resistance and causes right ventricular (RV) hypertrophy. Enhancement of the late sodium current (INaL) may result from hypertrophic remodelling. The study tests whether: (i) constitutive INaL enhancement may occur as part of PAH-induced myocardial remodelling; (ii) ranolazine (RAN), a clinically available INaL blocker, may prevent constitutive INaL enhancement and PAH-induced myocardial remodelling. METHODS AND RESULTS: PAH was induced in rats by a single monocrotaline (MCT) injection [60 mg/kg intraperitoneally (i.p.)]; studies were performed 3 weeks later. RAN (30 mg/kg bid i.p.) was administered 48 h after MCT and washed-out 15 h before studies. MCT increased RV systolic pressure and caused RV hypertrophy and loss of left ventricular (LV) mass. In the RV, collagen was increased; myocytes were enlarged with T-tubule disarray and displayed myosin heavy chain isoform switch. INaL was markedly enhanced; diastolic Ca(2+) was increased and Ca(2+) release was facilitated. K(+) currents were down-regulated and APD was prolonged. In the LV, INaL was enhanced to a lesser extent and cell Ca(2+) content was strongly depressed. Electrical remodelling was less prominent than in the RV. RAN completely prevented INaL enhancement and limited most aspects of PAH-induced remodelling, but failed to affect in vivo contractile performance. RAN blunted the MCT-induced increase in RV pressure and medial thickening in pulmonary arterioles. CONCLUSION: PAH induced remodelling with chamber-specific aspects. RAN prevented constitutive INaL enhancement and blunted myocardial remodelling. Partial mechanical unloading, resulting from an unexpected effect of RAN on pulmonary vasculature, might contribute to this effect. PMID- 25139748 TI - Angiogenesis and remodelling in human thoracic aortic aneurysms. AB - AIMS: Human thoracic aneurysm of the ascending aorta (TAA) is a chronic disease characterized by dilatation of the aortic wall, which can progress to vessel dissection and rupture. TAA has several aetiologies, but all forms present common features, including tissue remodelling. Here, we determined and characterized the angiogenic process associated with TAA and its relation with wall remodelling. METHODS AND RESULTS: Immunostaining for blood vessels showed an increased density of microvessels originating from the adventitia in the external medial layer of TAA compared with healthy aortas. Proteomic array analysis of 55 angiogenic factors in medial and adventitial layers showed different expression profiles in both tissue compartments between aneurysmal and healthy aortas. Quantification by ELISA confirmed that all forms of TAA contained higher levels of several pro- and anti-angiogenic factors, including angiopoietin-1 and -2, fibroblast growth factor-acidic, and thrombospondin-1, than that of healthy aortas. However, all groups showed comparable levels of vascular endothelial growth factor-A. Quantitative RT-PCR demonstrated that angiopoietins were overexpressed in TAA media. Immunostaining and electron microscopy revealed that neovessels had defective endothelial junctions and poor mural cell coverage. This incomplete structure was associated with the accumulation of plasminogen and albumin in the media of TAA. CONCLUSION: We describe, for the first time, leaky neovessel formation in TAA media in association with an imbalance of angiogenic factor levels. Although the initiating mechanisms of neo-angiogenesis in TAA and the potential aetiology-related differences remain to be determined, our results suggest that neo-angiogenesis could participate in TAA wall remodelling and weakening through deposition of blood-borne zymogens. PMID- 25139749 TI - Evaluation of the oxidative status in Oreochromis niloticus fed with tuna by product meal: possible human health impact. AB - The influence of tuna by-product meal (TBM) diets on the activities of antioxidant enzymes in the muscles, gill and kidney of tilapia was evaluated. The control diet (A0) used fish meal (FM) as the sole source of animal protein and the other three diets (A10-A30), 33%-100% of FM was substituted by TBM at 10% increments. The cytotoxicity of liver and muscles cytosol extracts in human liver cell HepG2 was undertaken. The activities of glutathione S-transferase, superoxide dismutase, catalase and TBARS values in the kidney of fish fed with diet A30 were significantly different (p<0.05) and no alterations were observed in muscle and gill anti-oxidant activities. Our study has confirmed that the cytosol extract does not exhibit cytotoxic effects on the HepG2 cells. These results indicate that the use of TBM as a total replacement for FM into tilapia diets seems to have oxidative stress, thus generating effect on fish metabolism. PMID- 25139750 TI - Hierarchical sampling for metastable conformers determines biomolecular recognition: the case of malectin and diglucosylated N-glycan interactions. AB - Structural information over the entire course of binding interactions based on the analyses of energy landscapes is described, which provides a framework to understand the events involved during biomolecular recognition. Conformational dynamics of malectin's exquisite selectivity for diglucosylated N-glycan (Dig-N glycan), a highly flexible oligosaccharide comprising of numerous dihedral torsion angles, are described as an example. For this purpose, a novel approach based on hierarchical sampling for acquiring metastable molecular conformations constituting low-energy minima for understanding the structural features involved in a biologic recognition is proposed. For this purpose, four variants of principal component analysis were employed recursively in both Cartesian space and dihedral angles space that are characterized by free energy landscapes to select the most stable conformational substates. Subsequently, k-means clustering algorithm was implemented for geometric separation of the major native state to acquire a final ensemble of metastable conformers. A comparison of malectin complexes was then performed to characterize their conformational properties. Analyses of stereochemical metrics and other concerted binding events revealed surface complementarity, cooperative and bidentate hydrogen bonds, water-mediated hydrogen bonds, carbohydrate-aromatic interactions including CH-pi and stacking interactions involved in this recognition. Additionally, a striking structural transition from loop to beta-strands in malectin CRD upon specific binding to Dig N-glycan is observed. The interplay of the above-mentioned binding events in malectin and Dig-N-glycan supports an extended conformational selection model as the underlying binding mechanism. PMID- 25139751 TI - Synthesis and structure-activity relationships of novel, potent, orally active hypoxia-inducible factor-1 inhibitors. AB - Hypoxia-inducible factor-1 (HIF-1) is the chief transcription factor regulating hypoxia-driven gene expression. HIF-1 overexpression is associated with poor prognosis in several cancers and therefore represents an attractive target for novel antitumor agents. We explored small molecule inhibitors of the HIF-1 pathway. Using high-throughput-screening, we identified benzanilide compound 1 (IC50=560 nM) as a seed. Subsequent extensive derivatization led to the discovery of compounds 43a and 51d, with anti-HIF-1 activities in vitro (IC50=21 and 0.47 nM, respectively), and in vivo. Additionally, 43a (12.5-100mg/kg) also displayed in vivo anti-tumor efficacy, without influencing body weight. PMID- 25139752 TI - Coevolution of caudal skeleton and tail feathers in birds. AB - Birds are capable of a wide range of aerial locomotor behaviors in part because of the derived structure and function of the avian tail. The tail apparatus consists of a several mobile (free) caudal vertebrae, a terminal skeletal element (the pygostyle), and an articulated fan of tail feathers that may be spread or folded, as well as muscular and fibroadipose structures that facilitate tail movements. Morphological variation in both the tail fan and the caudal skeleton that supports it are well documented. The structure of the tail feathers and the pygostyle each evolve in response to functional demands of differing locomotor behaviors. Here, I test whether the integument and skeleton coevolve in this important locomotor module. I quantified feather and skeletal morphology in a diverse sample of waterbirds and shorebirds using a combination of linear and geometric morphometrics. Covariation between tail fan shape and skeletal morphology was then tested using phylogenetic comparative methods. Pygostyle shape is found to be a good predictor of tail fan shape (e.g., forked, graduated), supporting the hypothesis that the tail fan and the tail skeleton have coevolved. This statistical relationship is used to reconstruct feather morphology in an exemplar fossil waterbird, Limnofregata azygosternon. Based on pygostyle morphology, this taxon is likely to have exhibited a forked tail fan similar to that of its extant sister clade Fregata, despite differing in inferred ecology and other aspects of skeletal anatomy. These methods may be useful in reconstructing rectricial morphology in other extinct birds and thus assist in characterizing the evolution of flight control surfaces in birds. PMID- 25139753 TI - Plasma estrone sulfate, clinical biochemistry, and milk yield of dairy cows carrying a fetus from a bull or its clone. AB - The aim of this article was to compare plasma estrone sulfate (E1SO4), clinical biochemistry, and milk yield of dairy cows carrying a female fetus from a bull (BULL) or from its clone (CLONE), evaluating also the relationship between the former variables and the birth weight of the newborn. Sixteen recipient dairy Friesian heifers (10 BULL and 7 CLONE) received a female embryo, obtained by in vitro embryo production and sexing by polymerase chain reaction with the semen of the BULL or the CLONE. Blood samples on all cows were obtained before feed distribution in the morning from jugular vein from 4 weeks before to 4 weeks after calving, to be analyzed for metabolic profile. The samples from late gestation were also analyzed for E1SO4 concentration. To separately assess the effect of calf birth weight (CBW), data were categorized as follows: low (<39 kg; BWT-A), mid (39-46 kg; BWT-B), and high (>46 kg; BWT-C). The plasma concentrations of beta-hydroxybutyric acid (BHB, P=0.019), Na (P=0.002), Cl (P=0.026), strong cation-anion balance (P=0.020), total bilirubin (P=0.054), and alpha1-globulin (P=0.044) were higher in prepartum BULL recipients than those in CLONE, whereas BHB (P=0.021) and Mg (P=0.090) were higher in postpartum BULL recipients, while no differences were recorded in the remaining postpartum parameters. The CBW class had significant interaction with week of gestation on antepartum plasma estrone sulfate (P=0.021), whereas CBW per se affected antepartum plasma BHB (P=0.021), and nonesterified fatty acids (NEFA; P=0.011) being higher in BWT-C which also had the lower NEFA concentration during postpartum. Milk yield was unaffected by the sire used, both for quantitative and qualitative aspects. Cows carrying heavier fetus (BWT-C) had a different lactation affected by month compared with the other 2 CBW groups. From these results, there were no differences between BULL and CLONE recipients. Estrone sulfate, BHB, and NEFA may be used to predict CBW and provide different nutritional management during gestation. PMID- 25139754 TI - Relationship between macrophages in mouse uteri and angiogenesis in endometrium during the peri-implantation period. AB - The objective of this study is to examine the change in macrophage numbers, inducible form of NO synthase (iNOS), and vascular endothelial growth factor (VEGF) expression both before and after embryo implantation in the uterine tissue of mice. In order to explore the mechanism of macrophages in endometrial angiogenesis, 8-week-old female mice were divided into three groups: pregnant group, pseudopregnant group (mated to male mice that had been vasectomized), and estrous group (unmated). Individuals from these three groups were sacrificed at time intervals D1.5 to D6.5. Formalin-fixed paraffin-embedded tissue was used for immunocytochemical localization of Mphi, iNOS, and VEGF utilizing standard methodology. The proportion of macrophages in the peripheral blood was determined by flow cytometry, and the relationship between macrophage, iNOS, and VEGF expression was analyzed. The proportion of peripheral blood macrophages in the pregnancy group was significantly higher than that in the other groups. The results of immunohistochemistry determined that the macrophages exhibited changes in both numbers and distribution. The number of macrophages in the endometrium of the pregnancy and pseudopregnancy groups was significantly higher than that in the control (estrous) group. In the pregnancy group, macrophage numbers dramatically decreased and gradually transferred to the perimetrium on D4.5. Immunostaining revealed strong staining in the pregnancy group and weaker staining in the pseudopregnant and control groups for both iNOS and VEGF. There was strong, dense immunostaining at the implantation site for both iNOS and VEGF, whereas light immunostaining was seen in interimplantation tissues on D5.5 to D6.5. In the pregnant group, peripheral blood and uterine macrophage proportions were negatively correlated, whereas the amount of macrophages, iNOS, and VEGF expression in the endometrium were positively correlated. The expression of iNOS and VEGF in the endometrium also displayed a strong positive correlation. In conclusion, during embryo implantation, macrophages levels decreased in the uterus, whereas the number of peripheral macrophages increased, suggesting that macrophages may migrate into the peripheral blood and uterus to adapt for pregnancy. Additionally, an increase in the expression of iNOS and VEGF was observed during the implantation window, implying that iNOS and VEGF may play an important role in promoting embryo implantation. The positive correlation between macrophages, iNOS, and VEGF in the implanting uterus implied that macrophages might regulate iNOS and VEGF during the implantation process. PMID- 25139755 TI - Influence of stimulation by electroejaculation on myocardial function, acid-base and electrolyte status, and hematobiochemical profiles in male dromedary camels. AB - This study was carried out to evaluate the effect of electroejaculation (EEJ) on myocardial function, acid-base balance, and hematobiochemical profiles in male dromedary camels. Twenty sexually mature, apparently healthy male camels were assigned to EEJ. Parallel, eight naturally mated male camels were enrolled as a control group. Three blood samples were collected from each camel: just before (T0), directly after (T1), and 24 hours after (T2) EEJ or natural mating. The serum concentrations of the cardiac biomarker troponin I (cTnI), blood gas parameters, and hematobiochemical profiles were determined. Nineteen camels were ejaculated by the end of the second circuit and one by the end of the first circuit. In both groups, the mean heart and respiratory rates had increased significantly immediately after the procedure, but returned to normal values 24 hours after the procedure. The mean serum concentration of cTnI had increased significantly in all camels after EEJ, but not in controls. However, at 24 hours post-EEJ, the serum concentration of cTnI did not differ significantly compared with baseline values. The blood pH and base excess had decreased, and the PCO2 and lactic acid had increased after EEJ. The EEJ provoked decreases in hematocrit and mean corpuscular volume. In the control group, the base excess, HCO3(-), TCO2, anion gap, and lactic acid increased slightly after mating but did not reach a significant level compared with premating values. It is concluded that EEJ in camels results in a reversible myocardial injury, changes in the acid-base status, and increase the lactic acid concentration. PMID- 25139756 TI - Importance of intense male sexual behavior for inducing the preovulatory LH surge and ovulation in seasonally anovulatory female goats. AB - The present study was carried out to determine whether the presence of photostimulated sedated male goats could stimulate the LH preovulatory surge and ovulation in seasonal anestrous goats. Sexually experienced male goats were treated with artificial long days (16 hours light per day) from 1 November to 15 January to stimulate their sexual activity in March and April, corresponding to the natural sexual rest. A female group of goats (n=20) was exposed to non sedated males who displayed an intense sexual behavior and provided strong odor (non-sedated group). Another female group of goats (n=20) was exposed to the photo-stimulated male goats, but these males were sedated with Xylazine 2% to prevent the expression of sexual behavior (sedated group). The sedated males also provided a strong odor. Females of both groups had full physical and visual contact with non-sedated or sedated males. In both groups, the males remained with females during 4 days. The LH preovulatory surge of 10 female goats per group was measured by determination of LH plasma concentrations in samples taken every 3 hours. In addition, in all goats, (n=20 by group), ovulation was determined by measuring plasma concentrations of progesterone. The proportion of female goats showing a preovulatory LH surge was higher in goats exposed to non sedated (10/10) than in those exposed to sedated bucks (0/10; P<0.0001). Similarly, most of does in contact with non-sedated males ovulated (19/20), but none of those in contact with sedated males did so (0/20; P<0.0001). We conclude that the expression of an intense sexual behavior by male goats is necessary to induce LH preovulatory surge and ovulation in seasonally anovulatory goats. PMID- 25139757 TI - Novel hinge-binding motifs for Janus kinase 3 inhibitors: a comprehensive structure-activity relationship study on tofacitinib bioisosteres. AB - The Janus kinases (JAKs) are a family of cytosolic tyrosine kinases crucially involved in cytokine signaling. JAKs have been demonstrated to be valid targets in the treatment of inflammatory and myeloproliferative disorders, and two inhibitors, tofacitinib and ruxolitinib, recently received their marketing authorization. Despite this success, selectivity within the JAK family remains a major issue. Both approved compounds share a common 7H-pyrrolo[2,3-d]pyrimidine hinge binding motif, and little is known about modifications tolerated at this heterocyclic core. In the current study, a library of tofacitinib bioisosteres was prepared and tested against JAK3. The compounds possessed the tofacitinib piperidinyl side chain, whereas the hinge binding motif was replaced by a variety of heterocycles mimicking its pharmacophore. In view of the promising expectations obtained from molecular modeling, most of the compounds proved to be poorly active. However, strategies for restoring activity within this series of novel chemotypes were discovered and crucial structure-activity relationships were deduced. The compounds presented may serve as starting point for developing novel JAK inhibitors and as a valuable training set for in silico models. PMID- 25139758 TI - Effects of the biosynthesis and signaling pathway of ecdysterone on silkworm (Bombyx mori) following exposure to titanium dioxide nanoparticles. AB - Silkworm (Bombyx mori), a model Lepidoptera insect, is economically important. Its growth and development are regulated by endogenous hormones. During the process of transition from larvae to pupae, 20-hydroxyecdysone (20E) plays an important role. The recent surge in consumer products and applications using metallic nanoparticles has increased the possibility of human or ecosystem exposure due to their unintentional release into the environment. We investigated the effects of exposure to titanium dioxide nanoparticles (TiO2 NPs) on the action of 20E in B. mori. Titanium dioxide nanoparticle treatment shortened the molting duration by 8 hr and prolonged the molting peak period by 10 %. Solexa sequencing profiled the changes in gene expression in the brain of fifth-instar B. mori in response to TiO2NPS exposure for 72 hr, to address the effects on hormone metabolism and regulation. Thirty one genes were differentially expressed. The transcriptional levels of pi3k and P70S6K, which are involved in the target of the rapamycin (TOR) signaling pathway, were up-regulated. Transcriptional levels of four cytochrome P450 genes, which are involved in 20E biosynthesis, at different developmental stages (48, 96, 144, and 192 hr) at 5th instars of all displayed trends of increasing expression. Simultaneously, the ecdysterone receptors, also displayed increasing trends. The 20E titers at four developmental stages during the 5th instar were 1.26, 1.23, 1.72, and 2.16 fold higher, respectively, than the control group. These results indicate that feeding B. mori with TiO2 NPs stimulates 20E biosynthesis, shortens the developmental progression, and reduces the duration of molting. Thus, application of TiO2 NPs is of high significance for saving the labor force in sericulture, and our research provides a reference for the ecological problems in the field of Lepidoptera exposured to titanium dioxide nanoparticles. PMID- 25139759 TI - Associations between liver enzymes, psychopathological and clinical features in eating disorders. AB - Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are frequently reported in patients with anorexia nervosa (AN) and in subjects who are overweight or with hyperlipidemia, which can be found to be associated with binge eating disorder (BED) and bulimia nervosa (BN). Liver functioning and psychopathological features have been evaluated in 43 patients with AN, 33 with BN, and 32 with BED. Body mass index was found to be inversely associated with AST and ALT in AN, and directly associated with AST and ALT in BED. A positive association between ALT and AST and body shape concern in AN was observed. Liver enzymes could be considered as an index of severity in AN and BED patients. PMID- 25139760 TI - Colloidal crystal grain boundary formation and motion. AB - The ability to assemble nano- and micro- sized colloidal components into highly ordered configurations is often cited as the basis for developing advanced materials. However, the dynamics of stochastic grain boundary formation and motion have not been quantified, which limits the ability to control and anneal polycrystallinity in colloidal based materials. Here we use optical microscopy, Brownian Dynamic simulations, and a new dynamic analysis to study grain boundary motion in quasi-2D colloidal bicrystals formed within inhomogeneous AC electric fields. We introduce "low-dimensional" models using reaction coordinates for condensation and global order that capture first passage times between critical configurations at each applied voltage. The resulting models reveal that equal sized domains at a maximum misorientation angle show relaxation dominated by friction limited grain boundary diffusion; and in contrast, asymmetrically sized domains with less misorientation display much faster grain boundary migration due to significant thermodynamic driving forces. By quantifying such dynamics vs. compression (voltage), kinetic bottlenecks associated with slow grain boundary relaxation are understood, which can be used to guide the temporal assembly of defect-free single domain colloidal crystals. PMID- 25139761 TI - Revisiting the adaptive and maladaptive effects of crossmodal plasticity. AB - One of the most striking demonstrations of experience-dependent plasticity comes from studies of sensory-deprived individuals (e.g., blind or deaf), showing that brain regions deprived of their natural inputs change their sensory tuning to support the processing of inputs coming from the spared senses. These mechanisms of crossmodal plasticity have been traditionally conceptualized as having a double-edged sword effect on behavior. On one side, crossmodal plasticity is conceived as adaptive for the development of enhanced behavioral skills in the remaining senses of early-deaf or blind individuals. On the other side, crossmodal plasticity raises crucial challenges for sensory restoration and is typically conceived as maladaptive since its presence may prevent optimal recovery in sensory-re-afferented individuals. In the present review we stress that this dichotomic vision is oversimplified and we emphasize that the notions of the unavoidable adaptive/maladaptive effects of crossmodal reorganization for sensory compensation/restoration may actually be misleading. For this purpose we critically review the findings from the blind and deaf literatures, highlighting the complementary nature of these two fields of research. The integrated framework we propose here has the potential to impact on the way rehabilitation programs for sensory recovery are carried out, with the promising prospect of eventually improving their final outcomes. PMID- 25139762 TI - Contributions of different kainate receptor subunits to the properties of recombinant homomeric and heteromeric receptors. AB - The tetrameric kainate receptors can be assembled from a combination of five different subunit subtypes. While GluK1-3 subunits can form homomeric receptors, GluK4 and GluK5 require a heteromeric partner to assemble, traffic to the membrane surface, and produce a functional channel. Previous studies have shown that incorporation of a GluK4 or GluK5 subunit changes both receptor pharmacology and channel kinetics. We directly compared the functional characteristics of recombinant receptors containing either GluK4 or GluK5 in combination with the GluK1 or GluK2 subunit. In addition, we took advantage of mutations within the agonist binding sites of GluK1, GluK2, or GluK5 to isolate the response of the wild-type partner within the heteromeric receptor. Our results suggest that GluK1 and GluK2 differ primarily in their pharmacological properties, but that GluK4 and GluK5 have distinct functional characteristics. In particular, while binding of agonist to only the GluK5 subunit appears to activate the channel to a non desensitizing state, binding to GluK4 does produce some desensitization. This suggests that GluK4 and GluK5 differ fundamentally in their contribution to receptor desensitization. In addition, mutation of the agonist binding site of GluK5 results in a heteromeric receptor with a glutamate sensitivity similar to homomeric GluK1 or GluK2 receptors, but which requires higher agonist concentrations to produce desensitization. This suggests that onset of desensitization in heteromeric receptors is determined more by the number of subunits bound to agonist than by the identity of those subunits. The distinct, concentration-dependent properties observed with heteromeric receptors in response to glutamate or kainate are consistent with a model in which either subunit can activate the channel, but in which occupancy of both subunits within a dimer is needed to allow desensitization of GluK2/K5 receptors. PMID- 25139763 TI - High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physicochemical characterization, in vitro aerosol dispersion, and cellular studies. AB - Inhalable lung surfactant-based carriers composed of synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG), along with paclitaxel (PTX), were designed and optimized as respirable dry powders using organic solution co-spray-drying particle engineering design. These materials can be used to deliver and treat a wide variety of pulmonary diseases with this current work focusing on lung cancer. In particular, this is the first time dry powder lung surfactant-based particles have been developed and characterized for this purpose. Comprehensive physicochemical characterization was carried out to analyze the particle morphology, surface structure, solid state transitions, amorphous character, residual water content, and phospholipid bilayer structure. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy. PTX loading was high, as quantified using UV-VIS spectroscopy, and sustained PTX release was measured over weeks. In vitro cellular characterization on lung cancer cells demonstrated the enhanced chemotherapeutic cytotoxic activity of paclitaxel from co-spray-dried DPPC/DPPG (co-SD DPPC/DPPG) lung surfactant-based carrier particles and the cytotoxicity of the particles via pulmonary cell viability analysis, fluorescent microscopy imaging, and transepithelial electrical resistance (TEER) testing at air-interface conditions. In vitro aerosol performance using a Next Generation ImpactorTM (NGITM) showed measurable powder deposition on all stages of the NGI and was relatively high on the lower stages (nanometer aerodynamic size). Aerosol dispersion analysis of these high performing DPIs showed mass median diameters (MMADs) that ranged from 1.9 to 2.3 MUm with excellent aerosol dispersion performance as exemplified by high values of emitted dose, fine particle fractions, and respirable fractions. PMID- 25139764 TI - Photodegradation of moxifloxacin in aqueous and organic solvents: a kinetic study. AB - The kinetics of photodegradation of moxifloxacin (MF) in aqueous solution (pH 2.0 12.0), and organic solvents has been studied. MF photodegradation is a specific acid-base catalyzed reaction and follows first-order kinetics. The apparent first order rate constants (kobs) for the photodegradation of MF range from 0.69 * 10( 4) (pH 7.5) to 19.50 * 10(-4) min(-1) (pH 12.0), and in organic solvents from 1.24 * 10(-4) (1-butanol) to 2.04 * 10(-4) min(-1) (acetonitrile). The second order rate constant (k2) for the [H(+)]-catalyzed and [OH(-)]-catalyzed reactions are 6.61 * 10(-2) and 19.20 * 10(-2) M(-1) min(-1), respectively. This indicates that the specific base-catalyzed reaction is about three-fold faster than that of the specific acid-catalyzed reaction probably as a result of the rapid cleavage of diazabicyclononane side chain in the molecule. The kobs-pH profile for the degradation reactions is a V-shaped curve indicating specific acid-base catalysis. The minimum rate of photodegradation at pH 7-8 is due to the presence of zwitterionic species. There is a linear relation between kobs and the dielectric constant and an inverse relation between kobs and the viscosity of the solvent. Some photodegraded products of MF have been identified and pathways proposed for their formation in acid and alkaline solutions. PMID- 25139765 TI - Abdominal cocoon as a presenting feature of systemic lupus erythematous. A rare presentation. PMID- 25139766 TI - Extracavitary primary effusion lymphoma: clinical, morphological, phenotypic and cytogenetic characterization using nuclei enrichment technique. AB - AIMS: Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma, which typically manifests as malignant effusion in the body cavities. However, extracavitary solid variants are also described. The aim of this study was to investigate copy number aberrations in two cases of solid PEL at their first occurrences and relapse by applying a newly developed methodology of tumour nuclei enrichment. METHODS AND RESULTS: Using histological and genetic techniques, a novel protocol for tumour nuclei enrichment by flow sorting and array-comparative genomic hybridization, we characterized two cases of extracavitary PEL, one of which later relapsed as effusion. Both primary tumours were positive for HHV8 and EBV, confined to lymph nodes, and aberrantly expressed CD3, yet displaying clonal immunoglobulin gene rearrangements indicating B-cell origin. Cytogenetic characterization of primary tumours revealed modest number of aberrations, partially overlapping with previously reported affected loci. The effusional relapse in case 1 was cytogenetically related to the primary tumour but showed dramatic increase of chromosomal instability. CONCLUSIONS: We for the first time demonstrate a cytogenetic relationship between solid and effusional presentations of PEL. Moreover, we provide an indirect evidence of multiple malignant clones, which gave rise to clonally-related, yet karyotypically different relapsing lymphoma manifestations. PMID- 25139767 TI - The clinical interpretation of peritoneal equilibration test. PMID- 25139768 TI - Responses of five Mediterranean halophytes to seasonal changes in environmental conditions. AB - In their natural habitats, different mechanisms may contribute to the tolerance of halophytes to high soil salinity and other abiotic stresses, but their relative contribution and ecological relevance, for a given species, remain largely unknown. We studied the responses to changing environmental conditions of five halophytes (Sarcocornia fruticosa, Inula crithmoides, Plantago crassifolia, Juncus maritimus and J. acutus) in a Mediterranean salt marsh, from summer 2009 to autumn 2010. A principal component analysis was used to correlate soil and climatic data with changes in the plants' contents of chemical markers associated with stress responses: ions, osmolytes, malondialdehyde (MDA, a marker of oxidative stress) and antioxidant systems. Stress tolerance in S. fruticosa, I. crithmoides and P. crassifolia (all succulent dicots) seemed to depend mostly on the transport of ions to aerial parts and the biosynthesis of specific osmolytes, whereas both Juncus species (monocots) were able to avoid accumulation of toxic ions, maintaining relatively high K(+)/Na(+) ratios. For the most salt-tolerant taxa (S. fruticosa and I. crithmoides), seasonal variations of Na(+), Cl(-), K(+) and glycine betaine, their major osmolyte, did not correlate with environmental parameters associated with salt or water stress, suggesting that their tolerance mechanisms are constitutive and relatively independent of external conditions, although they could be mediated by changes in the subcellular compartmentalization of ions and compatible osmolytes. Proline levels were too low in all the species to possibly have any effect on osmotic adjustment. However except for P. crassifolia-proline may play a role in stress tolerance based on its 'osmoprotectant' functions. No correlation was observed between the degree of environmental stress and the levels of MDA or enzymatic and non-enzymatic antioxidants, indicating that the investigated halophytes are not subjected to oxidative stress under natural conditions and do not, therefore, need to activate antioxidant defence mechanisms. PMID- 25139769 TI - Effect of saline water on seed germination and early seedling growth of the halophyte quinoa. AB - Salinization is increasing on a global scale, decreasing average yields for most major crop plants. Investigations into salt resistance have, unfortunately, mainly been focused on conventional crops, with few studies screening the potential of available halophytes as new crops. This study has been carried out to investigate the mechanisms used by quinoa, a facultative halophytic species, in order to cope with high salt levels at various stages of its development. Quinoa is regarded as one of the crops that might sustain food security in this century, grown primarily for its edible seeds with their high protein content and unique amino acid composition. Although the species has been described as a facultative halophyte, and its tolerance to salt stress has been investigated, its physiological and molecular responses to seawater (SW) and other salts have not been studied. We evaluated the effects of SW and different salts on seed germination, seedling emergence and the antioxidative pathway of quinoa. Seeds were germinated in Petri dishes and seedlings grown in pots with SW solutions (25, 50, 75 and 100 %) and NaCl, CaCl2, KCl and MgCl2 individually, at the concentrations in which they are present in SW. Our results demonstrated that all salts, at lower concentrations, increased the germination rate but not the germination percentages, compared with control (pure water). Conversely, seedlings were differently affected by treatments in respect to salt type and concentration. Growth parameters affected were root and shoot length, root morphology, fresh and dry weight, and water content. An efficient antioxidant mechanism was present in quinoa, activated by salts during germination and early seedling growth, as shown by the activities of antioxidant enzymes. Total antioxidant capacity was always higher under salt stress than in water. Moreover, osmotic and ionic stress factors had different degrees of influence on germination and development. PMID- 25139770 TI - Control of main risk factors after ischaemic stroke across Europe: data from the stroke-specific module of the EUROASPIRE III survey. AB - BACKGROUND: Previous cross-sectional surveys in different European countries within the EUROASPIRE programme demonstrated a high prevalence of modifiable risk factors, unhealthy lifestyles and inadequate drug treatment in coronary heart disease patients. Comparable data for ischaemic stroke patients is lacking. METHODS: A stroke-specific study module was added to the EUROASPIRE III core survey. This cross-sectional multicentre survey included consecutive patients with first-ever ischaemic stroke from four European countries. Data were obtained from medical records, patient interviews and patient examinations within 6-36 months after the stroke event. Control of modifiable risk factors after stroke was evaluated against contemporary European guidelines. RESULTS: A total of 881 patients was recruited. Median age was 66 years, 37.5% were female; average time from the stroke event to interview was 550 days. At the time of the interview, 17.6% of stroke patients smoked cigarettes, 35.5% had a body mass index >=30 kg/m(2), 62.4% showed elevated blood pressure and 75.7% exhibited elevated LDL cholesterol levels. Antiplatelet drugs or oral anticoagulants were used by 87.2%, antihypertensive medication by 84.4% and statins by 56.8% of stroke patients. Among patients using antihypertensive drugs and lipid-lowering medication at the time of the interview, 34.3% and 34.4%, respectively, achieved target blood pressure and total cholesterol values according to current European guidelines. CONCLUSION: The EUROASPIRE III stroke-specific module shows that secondary prevention and risk factor control in patients after ischaemic stroke need to be improved in four European centres at the time of the study since about half of patients are not achieving risk factor targets defined in European guidelines. PMID- 25139771 TI - New myocardial infarction definition affects incidence, mortality, hospitalization rates and prognosis. AB - AIMS: To analyse differences in myocardial infarction incidence, mortality and hospitalization rates, 28-day case-fatality and two-year prognosis using two myocardial infarction case definitions: the classical World Health Organization definition (1994) and the European Society of Cardiology/American College of Cardiology definition (2000), which added cardiac troponin as a diagnostic biomarker. DESIGN: Population-based cohort of 4170 consecutive myocardial infarction patients aged 35-74 years from Girona (Spain) recruited between 2002 and 2009. METHODS: Incidence, mortality rates standardized to the European population and 28-day case-fatality were calculated. To estimate the association between case definition and prognosis, Cox models were fitted. RESULTS: Use of the 2000 European Society of Cardiology/American College of Cardiology definition significantly increased myocardial infarction incidence per 100,000 population (238.3 vs. 274.5 in men and 54.1 vs. 69.7 in women). Applying this definition decreased the 28-day case-fatality rate from 26.9% to 23.4% in men, and from 31.0% to 24.1% in women. In the acute phase, patients diagnosed only by increased troponins were significantly less treated with thrombolysis (34.4% vs. 2.0%), angiotensin-converting enzyme inhibitors (71.7% vs. 65.0%) and percutaneous coronary intervention (41.1% vs. 31.7%). Case-fatality at 28 days was significantly better in cases diagnosed only by troponin increase (0.2 % vs. 9.7%), but two-year cardiovascular mortality was higher (7.5% vs. 3.7%). CONCLUSIONS: Inclusion of cardiac troponins in myocardial infarction diagnosis increased annual incidence and decreased case-fatality. Diagnosis based only on increased troponins was associated with worse outcome. This group of patients at high risk of death should receive aggressive secondary prevention therapy. PMID- 25139772 TI - Predictors of cardiovascular events in patients with systemic lupus erythematosus (SLE): a systematic review and meta-analysis. AB - BACKGROUND: Cardiovascular disease represents an important cause of morbidity and mortality in patients with a diagnosis of systemic lupus erythematosus (SLE), due to a complex interplay between traditional risk factors and disregulation of autoimmunity but uncertainty is still present about the most important predictors of cardiovascular events. OBJECTIVES: The aim of our work was to perform a collaborative systematic review on the main predictors of cardiovascular events in SLE patients. METHODS: PubMed and Cochrane were systematically searched for eligible studies on SLE and cardiovascular events between January 2008 and December 2012. Study features, patient characteristics and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate - 95% confidence intervals) and consistency of predictors was formally appraised. RESULTS: A total of 17,187 patients was included; of those, 93.1% were female and the median age was 39 years. After a median follow up period of 8 years, cardiovascular events presented in 25.4%, including acute myocardial infarction (4.1%) and stroke (7.3%). The most important predictors may be divided into traditional risk factors, such as male gender (OR 6.2, CI 95% 1.49-25), hyperlipidaemia (OR 3.9, CI 95% 1.57-9.71), familiar history of cardiac disease (OR 3.6, CI 95% 1.15-11.32) and hypertension (OR 3.5, CI 95% 1.65-7.54), and SLE-related features, such as the presence of auto-antibodies (OR 5.8 and 5.0, CI 95% 3.28-7.78) and neurological disorders (OR 5.2, CI 95% 2.0-13.9). A low correlation was shown for the importance of organ damage and SLE activity (respectively OR 1.4, CI 95% 1.09-4.44 and OR 1.2, CI 95% 1.2-1.2), as well as for age at diagnosis (OR 1.1, CI 95% 1.07-1.17). CONCLUSIONS: Cardiovascular events in SLE patients are caused by a multifactorial mechanism, including both traditional and disease-specific risk factors. A global valuation with an individual risk stratification based on both these features is important to correctly manage these patients in order to reduce negative outcomes. PMID- 25139773 TI - Molecular pathways regulating the formation of brown-like adipocytes in white adipose tissue. AB - Adipose tissue is functionally composed of brown adipose tissue and white adipose tissue. The unique thermogenic capacity of brown adipose tissue results from expression of uncoupling protein 1 in the mitochondrial inner membrane. On the basis of recent findings that adult humans have functionally active brown adipose tissue, it is now recognized as playing a much more important role in human metabolism than was previously thought. More importantly, brown-like adipocytes can be recruited in white adipose tissue upon environmental stimulation and pharmacologic treatment, and this change is associated with increased energy expenditure, contributing to a lean and healthy phenotype. Thus, the promotion of brown-like adipocyte development in white adipose tissue offers novel possibilities for the development of therapeutic strategies to combat obesity and related metabolic diseases. In this review, we summarize recent advances in understanding the molecular mechanisms involved in the recruitment of brown-like adipocyte in white adipose tissue. PMID- 25139774 TI - [Scrotal space-occupying lesions]. AB - Palpable scrotal masses are common scenarios in any clinical practice. These tumors can be painful or painless, can be intratesticular or extratesticular and be cystic or solid. The distinction between benign and malignant tumors is of utmost importance to enable an adequate and differentiated therapy of patients. In clinical diagnostics besides the medical history, examination of the inguinoscrotal region, laboratory diagnostics and ultrasound examination of the inguinoscrotal area play a decisive role. During the last few years the increased use of contrast-enhanced ultrasound has helped clinicians in differentiating scrotal tumors. Malignant tumors are of particular importance because this entity is the most frequent malignant disease among younger men and according to the Robert Koch Institute there are approximately 3900 new patients in Germany each year (Robert Koch Institute, Krebs in Deutschland 2007/2008 and 2012). PMID- 25139775 TI - Prediction of coronary plaque location on arteries having myocardial bridge, using finite element models. AB - This study was performed to evaluate the influences of the myocardial bridges on the plaque initializations and progression in the coronary arteries. The wall structure is changed due to the plaque presence, which could be the reason for multiple heart malfunctions. Using simplified parametric finite element model (FE model) of the coronary artery having myocardial bridge and analyzing different mechanical parameters from blood circulation through the artery (wall shear stress, oscillatory shear index, residence time), we investigated the prediction of "the best" position for plaque progression. We chose six patients from the angiography records and used data from DICOM images to generate FE models with our software tools for FE preprocessing, solving and post-processing. We found a good correlation between real positions of the plaque and the ones that we predicted to develop at the proximal part of the myocardial bridges with wall shear stress, oscillatory shear index and residence time. This computer model could be additional predictive tool for everyday clinical examination of the patient with myocardial bridge. PMID- 25139776 TI - Molecular diagnosis of infectious diarrhea: focus on enteric protozoa. AB - Robust detection of enteric protozoa is a critical step toward determining the etiology of diarrhea. Widespread use of conventional microscopy, culturing and antigen detection in both industrial and developing countries is limited by relatively low sensitivity and specificity. Refinements of these conventional approaches that reduce turnaround time and instrumentation have yielded strong alternatives for clinical and research use. However, advances in molecular diagnostics for protozoal, bacterial, viral and helminth infections offer significant advantages in studies seeking to understand pathogenesis, transmission and long-term consequences of infectious diarrhea. Quantitation of enteropathogen burden and highly multiplexed platforms for molecular detection dramatically improve predictive power in emerging models of diarrheal etiology, while eliminating the expense of multiple tests. PMID- 25139777 TI - Out-of-office blood pressure improves risk stratification in normotension and prehypertension people. AB - This review addresses to what extent out-of-office blood pressure, the ambulatory blood pressure monitoring and the self-measured home blood pressure, refines conventional blood pressure-based risk stratification across increasing blood pressure categories, in particular individuals assumed to be associated with no or only mildly increased risk. Compared with sustained normotension, individuals with prehypertension as well as masked hypertension tend to be developed to true hypertension. Ambulatory blood pressure measurement refines risk stratification among prehypertensive people. Home blood pressure is more useful for the prediction of cerebrovascular diseases than conventional blood pressure, by replacing information from conventional to home blood pressure in risk stratification system. Furthermore, the two participant-level meta-analyses demonstrated that the out-of-office blood pressure substantially refines risk stratification in normotension and prehypertension, particularly among participants with masked hypertension. Properly organized randomized clinical trials are required to demonstrate that identification and treatment of masked hypertension, compared with the current standard care based on conventional pressure, lead to the reduction of cardiovascular diseases in population and are cost-effective. PMID- 25139778 TI - Treatment of hypertension and metabolic syndrome: lowering blood pressure is not enough for organ protection, new approach-arterial destiffening. AB - Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage. Until now, the main approach to reduce CVRF-induced end organ damage was by normalization of CVRFs; this approach was found effective to reduce damage and cardiovascular (CV) events. However, a residual risk always remained even when CVRFs were optimally balanced. An additional risk factor which has an immense effect on the progression of end organ damage is aging. Aging is accompanied by gradual stiffening of the arteries which finally leads to CV events. Until recently, the process of arterial aging was considered as unmodifiable, but this has changed. Arterial stiffening caused by the aging process is similar to the changes seen as a result of CVRF-induced arterial damage. Actually, the presence of CVRFs causes faster arterial stiffening, and the extent of damage is proportional to the severity of the CVRF, the length of its existence, the patient's genetic factors, etc. Conventional treatments of osteoporosis and of hormonal decline at menopause are potential additional approaches to positively affect progression of arterial stiffening. The new approach to further decrease progression of arteriosclerosis, thus preventing events, is the prevention of age associated arterial structural changes. This approach should further decrease age associated arterial stiffening. A totally new promising approach is to study the possibility of affecting collagen, elastin, and other components of connective tissue that participate in the process of arterial stiffening. Reduction of pulse pressure by intervention in arterial stiffening process by novel methods as breaking collagen cross-links or preventing their formation is an example of future directions in treatment. This field is of enormous potential that might be revolutionary in inducing further significant reduction of cardiovascular events. PMID- 25139779 TI - Ambulatory blood pressure phenotypes and the risk for hypertension. AB - Ambulatory blood pressure (BP) monitoring provides valuable information on a person's BP phenotype. Abnormal ambulatory BP phenotypes include white-coat hypertension, masked hypertension, nocturnal nondipping, nocturnal hypertension, and high BP variability. Compared to people with sustained normotension (normal BP in the clinic and on ambulatory BP monitoring), the limited research available suggests that the risk of developing sustained hypertension (abnormal BP in the clinic and on ambulatory BP monitoring) over 5 to 10 years is approximately two to three times greater for people with white-coat or masked hypertension. More limited data suggest that nondipping might predate hypertension, and no studies, to our knowledge, have examined whether nocturnal hypertension or high ambulatory BP variability predict hypertension. Ambulatory BP monitoring may be useful in identifying people at increased risk of developing sustained hypertension, but the clinical utility for such use would need to be further examined. PMID- 25139780 TI - Obstructive sleep apnea and hypertension: a critical review. AB - Obstructive sleep apnea (OSA) is a prevalent sleep disorder which is characterized by recurrent upper closure with oxygen desaturation and sleep disruption. OSA increases the risk of vascular disorders in the form of stroke, myocardial infarction, congestive heart failure, and hypertension. The mechanisms underlying the vascular disorders are several and include intermittent hypoxia with release of cytokines, angiogenic inhibitors, free radicals, and adhesion molecules. During apneas, arterial blood pressure gradually rises and surges abruptly after the termination of apnea. Two thirds of patients with OSA will ultimately have diurnal hypertension. This review discusses the literature supporting the significant role of OSA in hypertension and the effect of OSA treatment on blood pressure. PMID- 25139781 TI - Psychosocial risk factors for hypertension: an update of the literature. AB - A growing body of research demonstrates that psychosocial factors play an important role in the development of hypertension. Previous reviews have identified several key factors (i.e., occupational stress) that contribute to the onset of hypertension; however, they are now outdated. In this review, we provide an updated synthesis of the literature from 2010 to April 2014. We identified 21 articles for inclusion in the review, of which there were six categories of psychosocial stressors: occupational stress, personality, mental health, housing instability, social support/isolation, and sleep quality. Sixteen of the studies reported an association between the psychosocial stressor and blood pressure. While several findings were consistent with previous literature, new findings regarding mediating and moderating factors underlying the psychosocial hypertension association help to untangle inconsistencies reported in the literature. Moreover, sleep quality is a novel additional factor that should undergo further exploration. Areas for future research based on these findings are discussed. PMID- 25139782 TI - Resistant or refractory hypertension: are they different? AB - Resistant hypertension (RHTN) consists in a condition where blood pressure (BP) levels remain uncontrolled despite the use of at least three drugs or if the control happens with four or more drugs. Throughout the last 50 years, it has been increasingly studied, and its phenotypes have been identified. The term refractory hypertension has been used concurrently with RHTN all those years, but in the last decade, it has been applied to the most afflicted part of RHTN- defined as the uncontrolled RHTN or as the uncontrolled RHTN who needs five or more drugs. Differences between those two phenotypes are being recently identified, especially classifying refractory subjects as having more: (1) cardiovascular risk, (2) target organ damage, (3) African-descending race, (4) coronary heart disease and myocardial ischemia, (5) aldosterone excess, (6) deregulation of adipokines, and (7) possible sympathetic hyperactivation. We review the most important studies in both resistant and refractory hypertension to gather the up-to-date data regarding the characteristics of these two high risk groups of patients. PMID- 25139783 TI - Occupational health nursing in hungary. AB - This article is the first about occupational health nursing in Hungary. The authors describe the Hungarian health care and occupational health care systems, including nursing education and professional organizations for occupational health nurses. The Fundamental Law of Hungary guarantees the right of every employee to healthy and safe working conditions, daily and weekly rest times and annual paid leave, and physical and mental health. Hungary promotes the exercise of these rights by managing industrial safety and health care, providing access to healthy food, supporting sports and regular physical exercise, and ensuring environmental protection. According to the law, the responsibility for regulation of the occupational health service lies with the Ministry of Human Resources. Safety regulations are under the aegis of the Ministry of National Economy. PMID- 25139784 TI - Policy perspectives on occupational stress. AB - Occupational stress is a major physical and mental hazard for many workers and has been found to contribute to cardiovascular disease, musculoskeletal disorders, mood disturbances, workplace injuries, and mental health problems. Health care utilization related to these physical and mental health problems costs employers billions of dollars annually. To combat this problem, employers should adopt a preventive approach and institute organizational and administrative changes that require the participation of both management and workers. This article reviews policies that could impact the quality of work life and influence organizational changes needed to achieve occupational health and safety. Occupational health nurses play a vital role in designing and implementing policies to improve work environments and reduce occupational stress. PMID- 25139785 TI - Health-related quality of life and functional outcomes from a randomized withdrawal study of long-term lisdexamfetamine dimesylate treatment in children and adolescents with attention-deficit/hyperactivity disorder. AB - BACKGROUND: The stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well tolerated treatment for the symptoms of attention deficit/hyperactivity disorder (ADHD). Positive impacts of LDX on health-related quality of life and functional impairment have previously been demonstrated in a 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in Europe. Maintenance of these broad benefits, as well as symptomatic control, is a key goal of long-term management of ADHD. OBJECTIVE: Secondary objectives of this multinational study in children and adolescents with ADHD were to assess the long-term maintenance of effectiveness of LDX in improving health-related quality of life and reducing functional impairment, as gauged using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE: PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively. METHODS: Patients aged 6-17 years with diagnosed ADHD and a baseline ADHD Rating Scale IV total score of at least 28 were enrolled from the previous European study and from US sites. Patients who completed an open-label LDX treatment period of at least 26 weeks were randomized (1:1) to continue on their optimized dose of LDX or to switch to placebo for a 6-week, double-blind, withdrawal period. Parents completed CHIP-CE: PRF and WFIRS-P questionnaires at weeks 0, 8 and 26 of the open-label period and at weeks 0 and 6 of the randomized-withdrawal period, or at early termination. The endpoint of each period was defined as the last visit with valid data. Effect sizes were the difference (LDX minus placebo) in least-squares (LS)-mean change from baseline to endpoint divided by root-mean-square error. P values were nominal and not adjusted for multiple comparisons. RESULTS: The open-label and randomized full analysis sets comprised 262 and 153 (LDX n = 76; placebo n = 77) patients, respectively. Mean pretreatment CHIP-CE: PRF T-scores were more than one standard deviation below the normative mean in four of the five domains, and there was significant improvement across all domains from baseline to endpoint of the open label period. In the randomized-withdrawal period, LS-mean CHIP-CE: PRF T-scores deteriorated in all domains in the placebo group, but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Risk Avoidance (effect size 0.829; p < 0.001), Achievement (0.696; p < 0.001) and Satisfaction (0.636; p < 0.001) domains. Mean pretreatment WFIRS-P scores were lowest in the Family domain and the Learning and School domain. WFIRS-P total score and scores in all domains improved significantly from baseline to endpoint of the open-label period. In the randomized-withdrawal period, LS-mean scores deteriorated in the placebo group but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Family, Learning and School, and Risky Activities domains and in total (effect size 0.908; p < 0.001). CONCLUSIONS: Using parent-rated instruments, long-term maintenance of the beneficial effect of LDX in multiple domains of health-related quality of life and functional impairment was demonstrated by comparison of treatment continuation and withdrawal under randomized, double-blind, placebo-controlled conditions. PMID- 25139786 TI - Effect of music in endoscopy procedures: systematic review and meta-analysis of randomized controlled trials. AB - OBJECTIVE: Endoscopies are common clinical examinations that are somewhat painful and even cause fear and anxiety for patients. We performed this systematic review and meta-analysis of randomized controlled trials to determine the effect of music on patients undergoing various endoscopic procedures. METHODS: We searched the Cochrane Library, Issue 6, 2013, PubMed, and EMBASE databases up to July 2013. Randomized controlled trials comparing endoscopies, with and without the use of music, were included. Two authors independently abstracted data and assessed risk of bias. Subgroup analyses were performed to examine the impact of music on different types of endoscopic procedures. RESULTS: Twenty-one randomized controlled trials involving 2,134 patients were included. The overall effect of music on patients undergoing a variety of endoscopic procedures significantly improved pain score (weighted mean difference [WMD] = -1.53, 95% confidence interval [CI] [-2.53, -0.53]), anxiety (WMD = -6.04, 95% CI [-9.61, -2.48]), heart rate (P = 0.01), arterial pressure (P < 0.05), and satisfaction score (SMD = 1.83, 95% CI [0.76, 2.91]). Duration of the procedure (P = 0.29), except for gastrointestinal endoscopy (P = 0.03), and sedative or analgesic medication dose (P = 0.23, P = 0.12, respectively) were not significantly decreased in the music group, compared with the control group. Furthermore, music had little effect for patients undergoing colposcopy and bronchoscopy in the subanalysis. CONCLUSION: Our meta-analysis suggested that music may offer benefits for patients undergoing endoscopy, except in colposcopy and bronchoscopy. PMID- 25139788 TI - PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitro hepatocellular carcinoma models. AB - BACKGROUND: Hepatocellular carcinoma is the third cause of cancer related death for which new treatment strategies are needed. Targeting DNA repair pathways to sensitize tumor cells to chemo- or radiotherapy is under investigation for the treatment of several cancers with poly(ADP-ribose) polymerase (PARP) inhibitors showing great potential. The aim of this preclinical study was to evaluate the expression of PARP and PARG genes in a panel of liver cancer cell lines and primary human hepatocytes, their DNA repair capacity and assess the impact on cell survival of PARP inhibitors alone and in combination with radiotherapy. METHODS: Quantitative PCR was used to measure PARP-1, -2, -3 and PARG mRNA levels and western blotting for PARP-1 protein expression and ADP-ribose polymer formation after exposure of cells to doxorubicin, a topoisomerase II poison. DNA repair capacity was assessed using an in vitro DNA lesion excision/synthesis assay and the effects on cell killing of the PARP inhibitor ABT-888 alone and in combination with ionizing radiation using clonogenic survival. RESULTS: Although a wide range in expression of the PARPs and PARG was found correlations between PARP-1 and PARP-2 mRNA levels and PARP-1 mRNA and protein levels were noted. However these expression profiles were not predictive of PARP activity in the different cell lines that also showed variability in excision/synthesis repair capacity. 4 of the 7 lines were sensitive to ABT-888 alone and the two lines tested showed enhanced radiosensitivity in the presence of ABT-888. CONCLUSIONS: PARP inhibitors combined with radiotherapy show potential as a therapeutic option for hepatocellular carcinoma. PMID- 25139789 TI - Cardiac autonomic dysfunction in patients with head-up tilt test-induced vasovagal syncope. AB - BACKGROUND: Vasovagal syncope (VVS) is the result of an autonomic reflex that has a final effect of reducing sympathetic drive and increasing vagal activity. However, whether syncopal symptoms are associated with pathological cardiac autonomic modulation is not fully known. We tested the hypothesis that cardiac autonomic function is impaired in patients with VVS. METHODS: Eighty-four consecutive patients (59 males; 48.8 +/- 20.9 years) with recurrent unexplained syncope were enrolled. The head-up tilt test (HUTT) was positive in 38 patients and negative in 46 patients. Cardiac autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability, plasma concentrations of norepinephrine, and (123) I-metaiodobenzylguanidine (MIBG) scintigraphy. RESULTS: BRS indices were significantly lower in the HUTT-positive group than in the HUTT negative group (6.1 +/- 5.5 mm Hg/s vs 9.8 +/- 7.6 mm Hg/s, P = 0.02). With regard to cardiac (123) I-MIBG scintigraphy, the mean heart-to-mediastinum ratio at the delayed phase tended to be lower in HUTT-positive than in HUTT-negative individuals, but this difference was not significant (2.75 +/- 0.55 vs 3.02 +/- 0.49, P = 0.08).The percent washout rate of (123) I-MIBG was significantly higher in the positive group compared with the negative group (40.7 +/- 13.1% vs 31.5 +/ 13.3%, P = 0.02). Multivariate logistic analysis revealed that the appearance of HUTT-induced VVS was predicted independently by a high percent washout rate of (123) I-MIBG (odds ratio, 0.954; 95% confidence interval, 0.903-0.998; P = 0.048). CONCLUSIONS: Our results suggest that pathological autonomic cardiac modulation may play a role in the appearance of syncope in VVS patients. PMID- 25139790 TI - Editorial overview: In vivo chemistry: Pushing the envelope. PMID- 25139791 TI - Age patterns of Kaposi's sarcoma incidence in a cohort of HIV-infected men. AB - The life expectancy for HIV-positive individuals has improved over time due to increasing access to highly active antiretroviral therapy (HAART). Yet, as the HIV-positive population ages, their risk of developing cancers also increases. Studies of Kaposi's sarcoma (KS) among elderly HIV-infected persons are quite limited. We examined the age patterns of KS incidence and an association between age and KS risk in a US cohort of 3458 HIV-infected men, the Multicenter AIDS Cohort Study (MACS). Poisson distribution was used to calculate incidence rates and respective 95% confidence intervals (95% CIs). Cox proportional hazards regression was performed to examine the association between age and KS risk. There were 534 incident KS cases with a total follow-up time of 25,134 person years. The overall KS incidence rate was 2.13 per 100 person-years (95% CI: 1.95 2.32) (Non-HAART users-ever: 5.57 per 100 person-years [95% CI: 5.09-6.10]; HAART users-ever: 0.39 per 100 person-years [95% CI: 0.31-0.51]). Overall, KS frequency and incidence declined with age, even in the oldest age group (p(trend) < 0.0001). However, among non-HAART users-ever, the oldest age group had the highest incidence rate ratio compared to younger individuals [15.01, 95% CI: 6.12 44.22]). While the incidence of KS decreased with age, older HIV-infected persons who do not receive HAART are still at increased risk of KS. As KS remains an important malignancy among HIV-infected persons, earlier HIV diagnoses and HAART initiation, particularly in older HIV-infected persons is warranted. PMID- 25139792 TI - Assessment of a fluorescent antibody test for the detection of antibodies against epizootic bovine abortion. AB - The current study was directed at developing and validating an indirect fluorescent antibody test (IFAT) capable of detecting antibodies specific for the agent of epizootic bovine abortion (aoEBA). Sensitivity and specificity was determined by comparing antibody titers from 114 fetuses infected with aoEBA with 68 fetuses diagnosed with alternate infectious etiologies. Data established specificity at 100% and sensitivity at 94.7% when cutoff criteria for a positive test were assigned at a titer of >=1,000. Potential cross-reactivity was noted in samples from 3 fetuses with antibody titers of 10 or100; all were infected with Gram-positive organisms. The remaining 65 fetuses infected with microbes other than aoEBA, and an additional 12 negative reference sera, did not have detectable titers. The IFAT-based serology assay is rapid, reproducible, and unaffected by fluid color or opacity. Total fetal immunoglobulin (Ig)G was also evaluated as an aid for diagnosing EBA. Significantly higher concentrations of IgG were identified in fetuses infected with aoEBA as compared to those with alternate infectious etiologies. The presence of IgG is a sensitive indicator of EBA and increases the specificity of FAT-based serologic diagnosis when titers are 10 or 100. Taken together, serology and IgG analyses suggest that the incidence of EBA may be underestimated. PMID- 25139793 TI - Variable-number tandem repeats genotyping used to aid and inform management strategies for a bovine Johne's disease incursion in tropical and subtropical Australia. AB - The application of variable-number tandem repeats (VNTR) genotyping of Mycobacterium avium subsp. paratuberculosis isolates to assist in investigating incidents of bovine Johne's disease in a low-prevalence region of Australia is described in the current study. Isolates from a response to detection of bovine Johne's disease in Queensland were compared with strains from national and international sources. The tandem application of mycobacterial interspersed repetitive unit (MIRU) and multilocus short sequence repeats (MLSSR) genotyping identified 2 strains, 1 that infected cattle on multiple properties with trace forward histories from a common infected property, and 1 genotypically different strain recovered from a single property. The former strain showed an identical genotype to an isolate from India. Neither strain showed a genotypic link to regions of Australia with a higher prevalence of the disease. Genotyping has indicated incursions from 2 independent sources. This intelligence has informed investigations into potential routes of entry and the soundness of ongoing control measures, and supported strategy and policy decisions regarding management of Mycobacterium avium subsp. paratuberculosis incursions for Queensland. PMID- 25139795 TI - The welfare impact of parallel imports: a structural approach applied to the German market for oral anti-diabetics. AB - We investigate the welfare impact of parallel imports using a large panel dataset containing monthly information on sales, ex-factory prices, and further product characteristics for all 649 anti-diabetic drugs sold in Germany between 2004 and 2010. We estimate a two-stage nested logit model of demand, and on the basis of an oligopolistic model of multi-product firms, we then recover the marginal costs and markups. We finally evaluate the effect of the parallel imports' policy by calculating a counterfactual scenario without parallel trade. According to our estimates, parallel imports reduce the prices for patented drugs by 11% and do not have a significant effect on prices for generic drugs. This amounts to an increase in the demand-side surplus by ?19 million per year (or ?130 million in total), which is relatively small compared with the average annual market size of around ?227 million based on ex-factory prices. The variable profits for the manufacturers of original drugs from the German market are reduced by ?18 million (or 37%) per year when parallel trade is allowed, yet only one third of this difference is appropriated by the importers. PMID- 25139796 TI - Use of lyophilised and powdered Gentiana lutea root in fresh beef patties stored under different atmospheres. AB - BACKGROUND: Gentiana lutea root is a medicinal herb that contains many active compounds which contribute to physiological effects, and it has recently attracted much attention as a natural source of antioxidants. The aim of this study was to evaluate the effects on the colour, pH, microbial activities, sensory quality and resistance to lipid oxidation (through the thiobarbituric acid method) during storage of beef patties containing different concentrations of G. lutea. Fresh beef patties were formulated with 0-5 g kg(-1) of G. lutea and 0 or 0.5 g kg(-1) of ascorbic acid and packed in two different atmospheres, Modified Atmosphere 1 (MAP1) and Modified Atmosphere 2 (MAP2), and stored at 4 +/ 1 degrees C for 10 days. MAP1 contained 20:80 (v/v) O2:CO2 and MAP2 contained 80:20 (v/v) O2:CO2. RESULTS: G. lutea extracts possessed antioxidant activity measured by the ferric reducing antioxidant power and the oxygen radical absorbance capacity assays. Beef patties containing 2 g kg(-1) of lyophilised G. lutea were stable towards lipid oxidation in both atmospheres (P < 0.05). Beef patties containing a combination of 2 g kg(-1) G. lutea and 0.5 g kg(-1) ascorbic acid showed significantly reduced changes in colour and in lipid oxidation (P < 0.05). CONCLUSION: The results from this study demonstrate the potential of G. lutea as a food ingredient in the design of healthier meat commodities. PMID- 25139797 TI - Metabolomic analysis of extreme freezing tolerance in Siberian spruce (Picea obovata). AB - Siberian spruce (Picea obovata) is one of several boreal conifer species that can survive at extremely low temperatures (ELTs). When fully acclimated, its tissues can survive immersion in liquid nitrogen. Relatively little is known about the biochemical and biophysical strategies of ELT survival. We profiled needle metabolites using gas chromatography coupled with mass spectrometry (GC-MS) to explore the metabolic changes that occur during cold acclimation caused by natural temperature fluctuations. In total, 223 metabolites accumulated and 52 were depleted in fully acclimated needles compared with pre-acclimation needles. The metabolite profiles were found to develop in four distinct phases, which are referred to as pre-acclimation, early acclimation, late acclimation and fully acclimated. Metabolite changes associated with carbohydrate and lipid metabolism were observed, including changes associated with increased raffinose family oligosaccharide synthesis and accumulation, accumulation of sugar acids and sugar alcohols, desaturation of fatty acids, and accumulation of digalactosylglycerol. We also observed the accumulation of protein and nonprotein amino acids and polyamines that may act as compatible solutes or cryoprotectants. These results provide new insight into the mechanisms of freezing tolerance development at the metabolite level and highlight their importance in rapid acclimation to ELT in P. obovata. PMID- 25139798 TI - Reduced gene expression levels of Munc13-1 and additional components of the presynaptic exocytosis machinery upon conditional targeting of Vglut2 in the adolescent mouse. AB - Presynaptic proteins orchestrate an intricate interplay of dynamic interactions in order to regulate quantal exocytosis of transmitter-filled vesicles, and their dysregulation might cause neurological and neuropsychiatric dysfunction. Mice carrying a spatiotemporal restriction in the expression of the Vesicular glutamate transporter 2 (Vglut2; aka Slc17a6) in the cortex, amygdala and hippocampal subiculum from the third postnatal week show a strong anxiolytic phenotype and certain behavioral correlates of schizophrenia. To further understand the molecular consequences of this targeted deletion of Vglut2, we performed an unbiased microarray analysis comparing gene expression levels in the subiculum of these conditional Vglut2 knockout mice (Vglut2f/f;CamKII cKO) to those in control littermates. Expression of Unc13C (Munc13-3), a member of the Unc/Munc family, previously shown to be important for glutamatergic transmission, was identified to be significantly down-regulated. Subsequent analysis by quantitative RT-PCR revealed a 50% down-regulation of Munc 13-1, the gene encoding the Unc/Munc subtype described as an essential component in the majority of glutamtergic synapses in the hippocampus. Genes encoding additional components of the presynaptic machinery were also found regulated, including Rab3A, RIM1alpha, as well as Syntaxin1 and Synaptobrevin. Altered expression levels of these genes were further found in the amygdala and in the retrosplenial group of the cortex, additional regions in which Vglut2 was conditionally targeted. These findings suggest that expression levels of Vglut2 might be important for the maintenance of gene expression in the presynaptic machinery in the adult mouse brain. Synapse 68:624-633, 2014. (c) 2014 Wiley Periodicals, Inc. PMID- 25139800 TI - Using Big Data to Track Trends in Medical Practice. PMID- 25139799 TI - Use of clarithromycin and roxithromycin and risk of cardiac death: cohort study. AB - OBJECTIVE: To assess the risk of cardiac death associated with the use of clarithromycin and roxithromycin. DESIGN: Cohort study. SETTING: Denmark, 1997 2011. PARTICIPANTS: Danish adults, 40-74 years of age, who received seven day treatment courses with clarithromycin (n = 160,297), roxithromycin (n = 588,988), and penicillin V (n = 4,355,309). MAIN OUTCOME MEASURES: The main outcome was risk of cardiac death associated with clarithromycin and roxithromycin, compared with penicillin V. Subgroup analyses were conducted according to sex, age, risk score, and concomitant use of drugs that inhibit the cytochrome P450 3A enzyme, which metabolises macrolides. RESULTS: A total of 285 cardiac deaths were observed. Compared with use of penicillin V (incidence rate 2.5 per 1000 person years), use of clarithromycin was associated with a significantly increased risk of cardiac death (5.3 per 1000 person years; adjusted rate ratio 1.76, 95% confidence interval 1.08 to 2.85) but use of roxithromycin was not (2.5 per 1000 person years; adjusted rate ratio 1.04, 0.72 to 1.51). The association with clarithromycin was most pronounced among women (adjusted rate ratios 2.83 (1.50 to 5.36) in women and 1.09 (0.51 to 2.35) in men). Compared with penicillin V, the adjusted absolute risk difference was 37 (95% confidence interval 4 to 90) cardiac deaths per 1 million courses with clarithromycin and 2 (-14 to 25) cardiac deaths per 1 million courses with roxithromycin. CONCLUSIONS: This large cohort study found a significantly increased risk of cardiac death associated with clarithromycin. No increased risk was seen with roxithromycin. Given the widespread use of clarithromycin, these findings call for confirmation in independent populations. PMID- 25139801 TI - Reasons for Delay in Time to Initiation of Adjuvant Chemotherapy for Colon Cancer. AB - PURPOSE: Adjuvant chemotherapy (AC) improves survival among patients with colon cancer (CC). Two meta-analyses have demonstrated a decrease in survival with increasing time to AC (TTAC). Here, we examine the predominant factors leading to delay in TTAC. METHODS: Individual medical records of 580 patients with CC who initiated AC August 2005-November 2010 at two large academic cancer centers in Eastern Ontario were reviewed. Information regarding patient, disease, and treatment characteristics, including time intervals between each step in the cancer care pathway from surgery to AC, was captured. Patients were then categorized into three groups for comparison: (I) postoperative complication, (II) oncologist- or patient-initiated delay, (III) no delay. These groups were compared using chi(2) tests and one-way analysis of variance. A multivariable logistic regression model was used to determine factors associated with TTAC > 8 weeks in all patients and in group 1 alone. RESULTS: TTAC among the three groups was (I) 10.1 +/- 2.7 weeks, (II) 10.5 +/- 3.6 weeks, (III) 8.5 +/- 2.1 weeks (P < .001). The only significant predictor of TTAC > 8 weeks on multivariable analysis in group I was route of AC via central venous catheter (odds ratio [OR] = 2.4; 95% CI, 1.2 to 4.9). When multivariable analysis was performed on all patients, the presence of postoperative complications (OR = 2.4; 95% CI, 1.6 to 3.8) and oncologist- or patient-initiated delay were the strongest predictors of delay (OR = 3.5; 95% CI, 2.1 to 6.0). The percentages of patients with TTAC > 8 weeks were (I) 76.4% (n = 110), (II) 81.4% (n = 92), (III) 57.9% (n = 187). CONCLUSIONS: In patients with no reason for delay, most experienced TTAC > 8 weeks. This likely reflects delays in referral, consultation, and chemotherapy booking. These health system factors are modifiable, and future quality improvement initiatives should focus on how to reduce them. PMID- 25139802 TI - Reply to A. Kolacevski et al. PMID- 25139803 TI - RR interval-respiratory signal waveform modeling in human slow paced and spontaneous breathing. AB - Our aim was to model the dependence of respiratory sinus arrhythmia (RSA) on the respiratory waveform and to elucidate underlying mechanisms of cardiorespiratory coupling. In 30 subjects, RR interval and respiratory signal were recorded during spontaneous and paced (0.1Hz/0.15Hz) breathing and their relationship was modeled by a first order linear differential equation. This model has two parameters: a0 (related to the instantaneous degree of abdominal expansion) and a1 (referring to the speed of abdominal expansion). Assuming that a0 represents slowly adapting pulmonary stretch receptors (SARs) and a1 SARs in coordination with other stretch receptors and central integrative coupling; then pulmonary stretch receptors relaying the instantaneous lung volume are the major factor determining cardiovagal output during inspiration. The model's results depended on breathing frequency with the least error occurring during slow paced breathing. The role of vagal afferent neurons in cardiorespiratory coupling may relate to neurocardiovascular diseases in which weakened coupling among venous return, arterial pressure, heart rate and respiration produces cardiovagal instability. PMID- 25139804 TI - Role of striatal NMDA receptor subunits in a model of paroxysmal dystonia. AB - Dystonia is a movement disorder in which abnormal plasticity in the basal ganglia has been hypothesized to play a critical role. In a model of paroxysmal dystonia, the dt(sz) mutant hamster, previous studies indicated striatal dysfunctions, including an increased long-term potentiation (LTP). Beneficial effects were exerted by subunit-unspecific antagonists at NMDA receptors, which blocked LTP. NR2B subtype selective antagonists aggravated dystonia after systemic treatment in dt(sz) hamsters, suggesting that beneficial effects involved the NR2A receptor subtype. In the present study, NVP-AAM077, an antagonist with preferential activity on NR2A-containing NMDA receptors, exerted significant antidystonic effects in mutant hamsters after systemic administration (20 and 30mg/kg i.p.) and delayed the onset of a dystonic episode after intrastriatal injections (0.12 and 0.24MUg). As shown by present electrophysiological examinations in corticostriatal slices of dt(sz) hamsters and non-dystonic control hamsters, NVP AAM077 (50nM) completely blocked LTP in dt(sz) slices, but did not exert significant effects on LTP in non-dystonic controls. In contrast, the NR2B antagonist Ro 25-6981 (1-10MUmol) reduced LTP to a lower extent in dt(sz) mutant hamsters than in control animals. By using quantitative RT-PCR, the NR2A/NR2B ratio was found to be increased in the striatum, but not in the cortex of mutant hamsters in comparison to non-dystonic controls. These data indicate that NR2A mediated activation may be involved in the pathophysiology of paroxysmal dystonia. Since significant antidystonic effects were observed after systemic administration of NVP-AAM077 already at well tolerated doses, antagonists with preferential activity on NR2A-containing NMDA receptors could be interesting candidates for the treatment of dystonia. PMID- 25139805 TI - Novel and improved cell recognition for diagnosis. PMID- 25139806 TI - Separating the signal from the noise: expanding flow cytometry into the sub micron range. PMID- 25139810 TI - New directions in management of SAPHO syndrome. AB - To talk about SAPHO syndrome means to discuss its entity. It is a great honour to me as guest editor to greet you and to present to you the following scientific articles dealing with different aspects of the SAPHO syndrome. We are pleased to welcome experts in the fields of epidemiology, etiology, clinical aspects, imaging procedures and treatment modalities. Furthermore, I have been grateful to be able to invite a review board to read the articles and to support the authors with scientific remarks and interesting corrections. First, we will start with the introduction by Prof. Dr. Koehler, University of Saarland, Germany, entitled "From sternoclavicluar hyperostosis (SCCH) to SAPHO syndrome - a European story?". Afterwards, Dr. Colina, PhD, Imola, Italy, with co-authors will discuss "the latest state of the art" concerning essential clinical and radiological characteristics of the SAPHO syndrome. The following chapter by Dr. Pfoehler, PhD, University of Saarland, Germany, describes in detail the important dermatological aspects of psoriatic disease and its subentity of palmoplantar pustolosis against a etiological, diagnostic, and therapeutic background to better understand the arthro-osteo-cutaneous character of the SAPHO syndrome. In this context, Dr. Gilles, PhD, University Hospital of Paris, France, with co authors then discuss the different hypotheses of immunology and the possible autoimmune etiology of SAPHO syndrome. Furthermore, Prof. Dr. Wollheim, University of Lund, Sweden, concludes and elucidates the genetic aspects of the disease. With the regard to different SAPHO manifestations in the childhood, I am thankful that Prof. Dr. Girschick, Pediatric Rheumatology Vivantes Center, Berlin, Germany, has contributed a scientific article dealing with "non-bacterial osteomyelitis in childhood". Last but not least, the article "Trends of SAPHO therapy: should we content?" from Dr. Rozin, PhD, Technion Haifa, Israel, focuses on the antirheumatic treatment modalities, including antibiotic treatment modalities which have been investigated in case series over the last 20 years. It was my intention that all authors touch on the genetic, diagnostic, and therapeutic aspects of SAPHO syndrome not to cause redundancies in the presentation but to discuss the central role of these aspects from a respectively different viewpoint - with the aim of gaining a deep insight into the etiopathogenesis and clinical aspects of SAPHO syndrome. PMID- 25139811 TI - Psoriasis vulgaris and psoriasis pustulosa - epidemiology, quality of life, comorbidities and treatment. AB - The prevalence of psoriasis is 2-3% in European Countries, therefore psoriasis is one of the most frequently occurring inflammatory skin diseases. Psoriasis results from an interaction of genetic factors and environmental conditions such as infections, smoking or intake of certain drugs. Psoriatic arthritis is diagnosed in about 20% of patients with psoriasis. Pustular forms are much more rarely seen and have a genetic background distinct from plaque psoriasis. Psoriasis is associated with a multitude of comorbidities such as rheumatoid arthritis, inflammatory bowel diseases, diabetes mellitus, obesity, hypertension and dysfunctions in lipid metabolism. Quality of life is markedly reduced in psoriasis patients and many of them suffer from depression and anxiety. An interdisciplinary treatment of psoriasis and its comorbidities is therefore essential. Today, adequate therapy according to medical guidelines is able to heal skin lesions and to improve quality of life. PMID- 25139812 TI - Rapid prototyped patient specific implants for reconstruction of orbital wall defects. AB - Defects of orbital walls can be reconstructed using implants. The authors report a safe and accurate method to reconstruct bone defects in the orbital area using patient specific implants. A detailed process description of computer aided design (CAD) reconstructive surgery (CRS) is introduced in this prospective study. The 3D volumetric virtual implant was design using MSCT data and PTCProEngineerTM 3D software. The intact orbital cavity of twelve patients was mirrored to the injured side. Specific ledges steered the implant into correct place. Postoperatively the position was assessed using image fusion. One implant (8%) was rejected due to chemical impurities, two (16%) had a false shape due to incorrect CAD. Data of thin bone did not transfer correctly to CAD and resulted in error. One implant (8%) was placed incorrectly. Duration of the CRS was in average 1.17 h, correspondingly 1.57 h using intraoperative bending technique. The CRS process has several critical stages, which are related to converting data and to incompatibility between software. The CRS process has several steps that need further studies. The data of thin bone may be lost and disturb an otherwise very precise technique. The risk of incorporating impurities into the implant must be carefully controlled. PMID- 25139813 TI - Synthesis, physicochemical, and anticonvulsant properties of new N-Mannich bases derived from pyrrolidine-2,5-dione and its 3-methyl analog. AB - A series of 22 new N-[(4-phenylpiperazin-1-yl)-methyl]-3-methyl-pyrrolidine-2,5 dione and pyrrolidine-2,5-dione derivatives were synthesized and evaluated for their anticonvulsant activities in the maximum electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests after intraperitoneal injection into mice. The neurotoxicity was determined applying the rotarod test. The in vivo results in mice showed that seven compounds were effective in the MES or/and scPTZ seizure tests. The quantitative evaluation in both tests after i.p. administration into mice revealed that the most active compounds were N-[{4-(3,4 dichlorophenyl)-piperazin-1-yl}-methyl]-3-methylpyrrolidine-2,5-dione (12) with ED50 = 16.13 mg/kg (MES), ED50 = 133.99 mg/kg (scPTZ) and N-[{4-(3,4 dichlorophenyl)-piperazin-1-yl}-methyl]-pyrrolidine-2,5-dione (23) with ED50 = 37.79 mg/kg (MES), ED50 = 128.82 mg/kg (scPTZ), whereas N-[{4-(3 trifluoromethylphenyl)-piperazin-1-yl}-methyl]-pyrrolidine-2,5-dione (24) was effective only in the MES test with ED50 = 16.37 mg/kg. These molecules showed higher potency and also lower neurotoxicity than the reference antiepileptic drugs such as ethosuximide and valproic acid. PMID- 25139814 TI - Hierarchical self-assembly of supramolecular hydrophobic metallacycles into ordered nanostructures. AB - We describe herein the hierarchical self-assembly of discrete supramolecular metallacycles into ordered fibers or spherical particles through multiple noncovalent interactions. A new series of well-defined metallacycles decorated with long alkyl chains were obtained through metal-ligand interactions, which were capable of aggregating into ordered fibroid or spherical nanostructures on the surface, mostly driven by hydrophobic interactions. In-depth studies indicated that the morphology diversity was originated from the structural information encoded in the metallacycles, including the number of alkyl chains and their spatial orientation. Interestingly, the morphology of the metallacycle aggregates could be tuned by changing the solvent polarity. These findings are of special significance since they provide a simple yet highly controllable approach to prepare ordered and tunable nanostructures from small building blocks by means of hierarchical self-assembly. PMID- 25139815 TI - Effects of solvent evaporation time on immediate adhesive properties of universal adhesives to dentin. AB - OBJECTIVE: To evaluate the microtensile bond strengths (MUTBS) and nanoleakage (NL) of three universal or multi-mode adhesives, applied with increasing solvent evaporation times. METHODS: One-hundred and forty caries-free extracted third molars were divided into 20 groups for bond strength testing, according to three factors: (1) Adhesive - All-Bond Universal (ABU, Bisco, Inc.), Prime&Bond Elect (PBE, Dentsply), and Scotchbond Universal Adhesive (SBU, 3M ESPE); (2) Bonding strategy - self-etch (SE) or etch-and-rinse (ER); and (3) Adhesive solvent evaporation time - 5s, 15s, and 25s. Two extra groups were prepared with ABU because the respective manufacturer recommends a solvent evaporation time of 10s. After restorations were constructed, specimens were stored in water (37 degrees C/24h). Resin-dentin beams (0.8mm(2)) were tested at 0.5mm/min (MUTBS). For NL, forty extracted molars were randomly assigned to each of the 20 groups. Dentin disks were restored, immersed in ammoniacal silver nitrate, sectioned and processed for evaluation under a FESEM in backscattered mode. Data from MUTBS were analyzed using two-way ANOVA (adhesive vs. drying time) for each strategy, and Tukey's test (alpha=0.05). NL data were computed with non-parametric tests (Kruskal-Wallis and Mann-Whitney tests, alpha=0.05). RESULTS: Increasing solvent evaporation time from 5s to 25s resulted in statistically higher mean MUTBS for all adhesives when used in ER mode. Regarding NL, ER resulted in greater NL than SE for each of the evaporation times regardless of the adhesive used. A solvent evaporation time of 25s resulted in the lowest NL for SBU-ER. SIGNIFICANCE: Residual water and/or solvent may compromise the performance of universal adhesives, which may be improved with extended evaporation times. PMID- 25139816 TI - What can fibromyalgia teach us about chronic pain? An emblematic condition to discuss mind and body concepts, predictive medicine and assessment of chronic condition management. PMID- 25139817 TI - More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: a meta-analysis examining six core symptoms. AB - This study aimed to characterize and compare the efficacy profile on six fibromyalgia syndrome (FM) core symptoms associated with pharmacologic and non pharmacologic treatments. We screened PubMed, Embase and the Cochrane Library for FM articles from 1990 to September 2012 to analyse randomized controlled trials comparing pharmacologic or non-pharmacologic treatments to placebo or sham. Papers including assessments of at least 2 of the 6 main FM symptom domains - pain, sleep disturbance, fatigue, affective symptoms (depression/anxiety), functional deficit and cognitive impairment - were selected for analysis. Studies exploring pharmacologic approaches (n = 21) were mainly dedicated to treating a small number of dimensions, mostly pain. They were of good quality but were not prospectively designed to simultaneously document efficacy for the management of multiple core FM symptom domains. Only amitriptyline demonstrated a significant effect on as many as three core FM symptoms, but it exhibited many adverse effects and was subject to early tachyphylaxis. Studies involving non pharmacologic approaches (n = 64) were typically of poorer quality but were more often dedicated to multidimensional targets. Pool therapy demonstrated significant effects on five symptom domains, repetitive transcranial magnetic stimulation on four domains, balneotherapy on three domains and exercise, cognitive behaviour therapy and massage on two domains each. Differences between pharmacologic and non-pharmacologic approaches may be related to different modes of action, tolerability profiles and study designs. Very few drugs in well designed clinical trials have demonstrated significant relief for multiple FM symptom domains, whereas non-pharmacologic treatments with weaker study designs have demonstrated multidimensional effects. Future therapeutic trials for FM should prospectively examine each of the core domains and should attempt to combine pharmacologic and non-pharmacologic therapies in well-designed clinical trials. PMID- 25139818 TI - Motor training-induced cortical plastic changes and its disruption by chronic pain: a puzzle with more pieces than expected. PMID- 25139819 TI - Introduction of a national herpes zoster (shingles) immunization programme and impact on neuropathic pain. PMID- 25139820 TI - Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance: the roles of long chain fatty acids. AB - Insulin resistance is characterized by hyperglycaemia, dyslipidaemia and oxidative stress prior to the development of type 2 diabetes mellitus. To date, a number of mechanisms have been proposed to link these syndromes together, but it remains unclear what the unifying condition that triggered these events in the progression of this metabolic disease. There have been a steady accumulation of data in numerous experimental studies showing the strong correlations between mitochondrial dysfunction, oxidative stress and insulin resistance. In addition, a growing number of studies suggest that the raised plasma free fatty acid level induced insulin resistance with the significant alteration of oxidative metabolism in various target tissues such as skeletal muscle, liver and adipose tissue. In this review, we herein propose the idea of long chain fatty acid induced mitochondrial dysfunctions as one of the key events in the pathophysiological development of insulin resistance and type 2 diabetes. The accumulation of reactive oxygen species, lipotoxicity, inflammation-induced endoplasmic reticulum stress and alterations of mitochondrial gene subset expressions are the most detrimental that lead to the developments of aberrant intracellular insulin signalling activity in a number of peripheral tissues, thereby leading to insulin resistance and type 2 diabetes. PMID- 25139821 TI - A rare disorder mimics otitis media: Langerhans cell histiocytosis of the temporal bone in a child with interstitial pulmonary fibrosis. AB - Langerhans cell histiocytosis (LCH) is a rare disease ranging from a benign to a rapidly fatal condition affecting young children predominantly, and is characterized by an abnormal clonal proliferation of Langerhans cells. We report a case of a 3-year-old child presenting with a 1-year history of otorrhea and otorrhagia followed by a 6-month history of postauricular swelling in the right ear. Imaging demonstrated a large mass of organized tissue. A biopsy was conducted, and the diagnosis of LCH was confirmed by histopathological and immunohistochemical examination. The child was treated with a 12-month course of vinblastine chemotherapy with prednisolone. No clinical evidence of recurrence was noticed after 3 years of follow-up. This rare case highlights the importance for otolaryngologists to keep LCH in mind for differential diagnosis in very young patients with symptoms and signs suggestive of acute mastoiditis or chronic otitis media. PMID- 25139822 TI - Mechanisms underlying chronic whiplash: contributions from an incomplete spinal cord injury? AB - OBJECTIVE: To explore the association between findings on advanced, but available, magnetic resonance imaging (MRI) sequences of the cervical spinal cord and muscular system, in tandem with biomechanical measures of maximum volitional plantar flexion torques as a proxy for a mild incomplete spinal cord injury. DESIGN: Observational case series. SETTING: University research laboratory. SUBJECTS: Three patients with chronic whiplash and one patient with history of whiplash injury but no current symptoms. METHODS: We measured lower extremity muscle fat, morphological changes in descending spinal cord pathways with advanced MRI applications and maximal activation of the plantar flexors. RESULTS: Larger magnitudes of lower extremity muscle fat corresponded to altered spinal cord anatomy and reductions in the ability to maximally activate plantar flexor torques in the three subjects with chronic whiplash. Such findings were not present in the recovered participant. CONCLUSIONS: The potential value of MRI to quantify neuromuscular degeneration in chronic whiplash is recognized. Larger scaled prospective studies are warranted before stronger conclusions can be drawn. PMID- 25139823 TI - High nuclear expression levels of histone-modifying enzymes LSD1, HDAC2 and SIRT1 in tumor cells correlate with decreased survival and increased relapse in breast cancer patients. AB - BACKGROUND: Breast cancer is a heterogeneous disease with a highly variable clinical outcome in which both genetic and epigenetic changes have critical roles. We investigated tumor expression levels of histone-modifying enzymes LSD1, HDAC2 and SIRT1 in relation with patient survival and tumor relapse in a retrospective cohort of 460 breast cancer patients. Additionally, we correlated expression levels with tumor differentiation and tumor cell proliferation. METHODS: Immunohistochemical staining for LSD1, HDAC2 and SIRT1 was performed on tissue microarrays of tumor and corresponding normal formalin-fixed paraffin embedded tissues from breast cancer patients. Median nuclear expression levels in tumor tissues were used to divide the patients into low and high expression categories. In combined expression analyses, patients were divided into four subgroups: 1, all enzymes below-median; 2, one enzyme above-median; 3, two enzymes above-median; 4, all three enzymes above-median. The Cox proportional hazard model was used for univariate and multivariate survival analyses. The Pearson Chi-square method was used to assess correlation of combined expression levels with tumor cell proliferation and tumor differentiation. RESULTS: Expression of LSD1 and SIRT1, but not of HDAC2, was significantly increased in tumor tissues compared to their normal counterparts (both p < 0.001). Multivariate survival analyses identified SIRT1 as independent prognostic factor for relapse-free survival (RFS) with a hazard ratio (HR) of 1.34 (95% CI = 1.04 1.74, p = 0.02). For overall survival (OS), no significant differences were found when the individual enzymes were analyzed. Analyses of combined expression levels of the three histone-modifying enzymes correlated with OS (p = 0.03) and RFS (p = 0.006) with a HR of respectively 1.49 (95% CI = 1.07-2.08) and 1.68 (95% CI = 1.16-2.44) in multivariate analyses and were also related to tumor differentiation (p < 0.001) and tumor cell proliferation (p = 0.002). CONCLUSIONS: When the combined expression levels were analyzed, high expression of LSD1, HDAC2 and SIRT1 showed shorter patient survival time and shorter time to tumor relapse and correlated with poor tumor differentiation and a high level of tumor cell proliferation. Expression of these histone-modifying enzymes might therefore be involved in breast cancer pathogenesis. PMID- 25139825 TI - Glucagon in the artificial pancreas: supply and marketing challenges. AB - The use of glucagon, in conjunction with insulin, in a dual chamber pump (artificial pancreas, AP) is a working goal for multiple companies and researchers. However, capital investment to create, operate, and maintain facilities with sufficient scale to produce enough glucagon to treat millions of patients, at a level of profit that makes it feasible, will be substantial. It can be assumed that the marketplace will expect the daily cost of glucagon (to the consumer) to be similar to the daily cost of insulin. After one subtracts wholesaler and pharmacy markup, there may be very few dollars remaining for the drug company to cover profit, capital expenditures, marketing, burden, and other costs. Without the potential for adequate margins, manufacturers may not be willing to take the risk. Assuming that the projections discussed in this article are in the right ballpark, advance planning for the supply for glucagon needs to start today and not wait for the AP to come to market. PMID- 25139826 TI - Efficient quantification and characterization of bacterial outer membrane derived nano-particles with flow cytometric analysis. AB - There currently exists no efficient and easy method for size profiling and counting of membranous nano-scale particles, such as bacterial outer membrane vesicles (OMVs). We present here a cost-effective and fast method capable of profiling and counting small sample volumes of nano-scale membranous vesicles with standard laboratory equipment without the need for any washing steps. OMV populations of different bacterial species are compared and even subpopulations of OMVs can be identified after a simple labelling procedure. Counting is possible over three orders of magnitude without any changes to the protocol. Protein contaminations do not alter the described measurements. PMID- 25139827 TI - Reply to a comment by Ludbrook, Holmes, and Stockwell: gender differences in alcohol demand. PMID- 25139828 TI - Effect of different drying methods on chlorophyll, ascorbic acid and antioxidant compounds retention of leaves of Hibiscus sabdariffa L. AB - BACKGROUND: Use of the indigenous, easily accessible leafy vegetable roselle (Hibiscus sabdariffa L.) for value addition is gaining impetus as its nutritive and nutraceutical compounds are exposed by investigations. Being a perishable, storage is challenging, hence different methods of drying have been an attractive alternative for its postharvest usage in foods without much compromising its quality and antioxidant potential. RESULTS: Room- and freeze-dried samples were found to have best quality in terms of colour, total flavonoid content (18.53 +/- 2.39 and 18.66 +/- 1.06 g kg(-1) respectively), total phenolic content (17.76 +/- 1.93 and 18.91 +/- 0.48 g kg(-1)), chlorophyll content (1.59 +/- 0.001 and 1.55 +/- 0.001 g kg(-1)) and ascorbic acid content (11.11 +/- 1.04 and 8.92 +/- 0.94 g kg(-1)) compared with those subjected to infrared, crossflow, microwave, oven or sun drying. Samples treated by room and freeze drying retained maximum antioxidant potential as shown by the phosphomolybdate method and the 2,2 diphenyl-1-picrylhydrazyl free radical-scavenging activity and ferric-reducing antioxidant power assays. Cold water and hot water extracts showed significantly higher total phenolic content and total antioxidant activity owing to the greater solubility of phenolics and destruction of cellular components in polar solvents than in organic solvents. CONCLUSION: The data obtained show the potential for retaining quality parameters of roselle leaf under suitable drying methods. PMID- 25139829 TI - MicroRNA-145 as one negative regulator of astrogliosis. AB - Astrogliosis occurs at the lesion site within days to weeks after spinal cord injury (SCI) and involves the proliferation and hypertrophy of astrocytes, leading to glia scar formation. Changes in gene expression by deregulated microRNAs (miRNAs) are involved in the process of central nervous system neurodegeneration. Here, we report that mir-145, a miRNA enriched in rat spinal neurons and astrocytes, was downregulated at 1 week and 1 month after SCI. Our in vitro studies using astrocytes prepared from neonatal spinal cord tissues indicated that potent inflammagen lipopolysaccharide downregulated mir-145 expression in astrocytes, suggesting that SCI-triggered inflammatory signaling pathways could play the inhibitory role in astrocytic mir-145 expression. To induce overexpression of mir-145 in astrocytes at the spinal cord lesion site, we developed a lentivirus-mediated pre-miRNA delivery system using the promoter of glial fibrillary acidic protein (GFAP), an astrocyte-specific intermediate filament. The results indicated that astrocyte-specific overexpression of mir-145 reduced astrocytic cell density at the lesion border of the injured spinal cord. In parallel, overexpression of mir-145 reduced the size of astrocytes and the number of related cell processes, as well as cell proliferation and migration. Through a luciferase reporter system, we found that GFAP and c-myc were the two potential targets of mir-145 in astrocytes. Together, the findings demonstrate the novel role of mir-145 in the regulation of astrocytic dynamics, and reveal that the downregulation of mir-145 in astrocytes is a critical factor inducing astrogliosis after SCI. GLIA 2015;63:194-205. PMID- 25139830 TI - The brassinosteroid signaling network-a paradigm of signal integration. AB - Many hormonal and environmental signals regulate common cellular and developmental processes in plants. While the molecular pathways that transduce these signals have each been studied in detail, how these pathways are wired into regulatory networks to provide the coordinated responses has remained an outstanding question. Recent studies of the brassinosteroid signaling network have revealed extensive signal integration through direct interactions between components of different signaling pathways. In particular, a circuit of interacting transcription regulators integrates many signaling pathways to enable coordinated and coherent regulation of seedling morphogenesis by hormonal and environmental signals. The recent studies support an emerging theme that complex networks of highly integrated signaling pathways underlie the high levels of developmental plasticity and environmental adaptability of plants. PMID- 25139831 TI - Transport of ginkgolides with different lipophilicities based on an hCMEC/D3 cell monolayer as a blood-brain barrier cell model. AB - AIMS: In this report, the transport of ginkgolides with different lipophilicities was investigated using an hCMEC/D3 cell monolayer as a blood-brain barrier (BBB) cell model in vitro in an attempt to explain ginkgolide transport path mediated by lipophilicity. MAIN METHODS: The log P values of ginkgolides were determined by measuring the distribution of the molecule between oil and water. Additionally, the cytotoxicity of ginkgolides on hCMEC/D3 cells was assayed with the MTT method. Ginkgolide contents were determined with an ultra performance liquid chromatograph equipped with an evaporative light scattering detector (ULPC ELSD) method. Apparent permeability coefficients (Papp) and efflux ratios (PappBL >AP/PappAP->BL) were then calculated to describe the transport characteristics of ginkgolide. KEY FINDINGS: The transport of ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J across the hCMEC/D3 cell monolayer was non-directional. Additionally, ginkgolide C transport on the cell monolayer was time- and concentration-dependent in the paracellular pathway controlled by cytochalasin D (a tight junction modulator). The transport of ginkgolide N, ginkgolide L, and ginkgolide K across the cell monolayer displayed clear directionality at low ginkgolide concentrations. This behavior indicated that the transport of ginkgolide N, ginkgolide L, and ginkgolide K was influenced by the transcellular pathway containing an efflux protein accompanied by the paracellular pathway for passive diffusion. Additionally, the transport of ginkgolide K was increased significantly by co-culturing with a P-gp inhibitor. SIGNIFICANCE: These findings provide important information for elucidating ginkgolide transport pathways and may be beneficial for the design of ginkgolide molecules with high neuroprotective effects. PMID- 25139832 TI - Induction of TRPV5 expression by small activating RNA targeting gene promoter as a novel approach to regulate cellular calcium transportation. AB - AIM: Promoter-targeted small activating RNAs (saRNAs) have been shown to be able to induce target gene expression, a mechanism known as RNA activation (RNAa). The present study tested whether saRNA can induce the overexpression of TRPV5 in human cells derived from the kidney and subsequently manipulate cell calcium uptake. MAIN METHODS: Three saRNAs complementary to the TRPV5 promoter were synthesized and transfected into cells. TRPV5 expression at the RNA and protein levels was analyzed by quantitative real-time PCR and Western blotting respectively. For functional study, transcellular Ca(2+) transportation was tested by fura-2 analysis. Dihydrotestosterone (DHT), a suppressor of cellular calcium transportation, was administered to challenge the activating effect of selected saRNA. KEY FINDINGS: One of these synthesized saRNAs, ds-2939, significantly induced the expression of TRPV5 at both mRNA and protein levels. Fura-2 analysis revealed that the intracellular Ca(2+) concentration was elevated by ds-2939. DHT treatment reduced transmembrane Ca(2+) transport, which was partially antagonized by ds-2939. SIGNIFICANCE: Our results suggest that a saRNA targeting TRPV5 promoter can be utilized to manipulate the transmembrane Ca(2+) transport by upregulating the expression of TRPV5 and may serve as an alternative for the treatment of Ca(2+) balance-related diseases. PMID- 25139833 TI - Prostaglandin E2 produced by inducible COX-2 and mPGES-1 promoting cancer cell proliferation in vitro and in vivo. AB - AIM: Many cancers originate and flourish in a prolonged inflammatory environment. Our aim is to understand the mechanisms of how the pathway of prostaglandin E2 (PGE2) biosynthesis and signaling can promote cancer growth in inflammatory environment at cellular and animal model levels. MAIN METHODS: In this study, a chronic inflammation pathway was mimicked with a stable cell line that over expressed a novel human enzyme consisting of cyclooxygenase isoform-2 (COX-2) linked to microsomal (PGE2 synthase-1 (mPGES-1)) for the overproduction of pathogenic PGE2. This PGE2-producing cell line was co-cultured and co-implanted with three human cancer cell lines including prostate, lung, and colon cancers in vitro and in vivo, respectively. KEY FINDINGS: Increases in cell doubling rates for the three cancer cell types in the presence of the PGE2-producing cell line were clearly observed. In addition, one of the four human PGE2 subtype receptors, EP1, was used as a model to identify PGE2-signaling involved in promoting the cancer cell growth. This finding was further proven in vivo by co-implanting the PGE2-producing cells line and the EP1-positive cancer cells into the immune deficient mice, after that, it was observed that the PGE2-producing cells promoted all three types of cancer formation in the mice. SIGNIFICANCE: This study clearly demonstrated that the human COX-2 linked to mPGES-1 is a pathway that, when mediated by the EP, is linked to promoting cancer growth in a chronic inflammatory environment. The identified pathway could be used as a novel target for developing and advancing anti-inflammation and anti-cancer interventions. PMID- 25139834 TI - Effects of intravenous cariporide on release of norepinephrine and myoglobin during myocardial ischemia/reperfusion in rabbits. AB - AIMS: To examine the effects of cariporide, a Na(+)/H(+) exchanger-1 inhibitor, on cardiac norepinephrine (NE) and myoglobin release during myocardial ischemia/reperfusion by applying a microdialysis technique to the rabbit heart. MAIN METHODS: In anesthetized rabbits, two dialysis probes were implanted into the left ventricular myocardium and were perfused with Ringer's solution. Cariporide (0.3mg/kg) was injected intravenously, followed by occlusion of the left circumflex coronary artery. During 30-min coronary occlusion followed by 30 min reperfusion, four consecutive 15-min dialysate samples (two during ischemia and two during reperfusion) were collected in vehicle and cariporide-treated groups. Dialysate myoglobin and NE concentrations were measured by immunochemistry and high-performance liquid chromatography, respectively. KEY FINDINGS: Dialysate myoglobin and NE concentrations increased significantly during myocardial ischemia/reperfusion in both vehicle and cariporide-treated groups (P<0.01 vs. baseline). In cariporide-treated group, dialysate myoglobin concentrations were significantly lower than those in vehicle group throughout ischemia/reperfusion (P<0.01 at 0-15 min of ischemia, P<0.05 at 15-30 min of ischemia, P<0.01 at 0-15 min of reperfusion, and P<0.01 at 15-30 min of reperfusion). However, dialysate NE concentrations in cariporide-treated group were lower than those in vehicle group only during ischemia (P<0.01 at 0-15 min of ischemia, and P<0.05 at 15-30 min of ischemia). SIGNIFICANCE: When administered before ischemia, cariporide reduces myoglobin release during ischemia/reperfusion and decreases NE release during ischemia. PMID- 25139835 TI - Discounting of delayed rewards: (A)theoretical interpretation of the Kirby questionnaire. AB - 111 Participants, recruited from Amazon's MTurk worker pool, completed Kirby's (2009) monetary choice questionnaire, which involves choosing between immediate, but smaller rewards and delayed, but larger rewards. Individual participants' responses were scored in three ways: first, by calculating the proportion of choices of the delayed rewards; second; using the scoring procedure described by Kirby et al. (1999) to estimate discounting rate (i.e., the value of the k parameter in a hyperbolic discounting function); and third, using logistic regression to estimate discounting rate (Wileyto et al., 2004). Individuals' scores calculated using the proportion measure and the logarithms of their estimated k values were very strongly correlated (rs>.97). In addition, the proportions of choices of small, medium, and large amounts of the delayed rewards were strongly correlated (rs>.80). Taken together, these results suggest that the relative ease of calculating the proportion measure does not require sacrificing reliability. Moreover, the proportion measure is atheoretical and very easy to calculate whereas estimating an individual's discounting rate requires assuming a theoretical model that may not be appropriate. Significant differences in the proportion of delayed reward choices were observed between the small, medium, and large delayed reward amounts, with smaller rewards being discounted more steeply than larger ones, replicating previous findings of magnitude effects. These results provide further validation of the proportion of delayed reward choices on the Kirby questionnaire as a measure of individual and group differences in discounting. PMID- 25139836 TI - Genome size estimates for crustaceans using Feulgen image analysis densitometry of ethanol-preserved tissues. AB - Crustaceans are enormously diverse both phylogenetically and ecologically, but they remain substantially underrepresented in the existing genome size database. An expansion of this dataset could be facilitated if it were possible to obtain genome size estimates from ethanol-preserved specimens. In this study, two tests were performed in order to assess the reliability of genome size data generated using preserved material. First, the results of estimates based on flash-frozen versus ethanol-preserved material were compared across 37 species of crustaceans that differ widely in genome size. Second, a comparison was made of specimens from a single species that had been stored in ethanol for 1-14 years. In both cases, the use of gill tissue in Feulgen image analysis densitometry proved to be a very viable approach. This finding is of direct relevance to both new studies of field-collected crustaceans as well as potential studies based on existing collections. PMID- 25139837 TI - Interplay between plasmid-mediated and chromosomal-mediated fluoroquinolone resistance and bacterial fitness in Escherichia coli. AB - OBJECTIVES: The aim of this study was to analyse the interplay among plasmid mediated qnr genes, alone or in combination with multiple chromosomal-mediated fluoroquinolone (FQ) resistance determinants, susceptibility to FQs and bacterial fitness in an isogenic Escherichia coli collection. METHODS: E. coli ATCC 25922 was used to modify or delete chromosomal genes. qnr genes were cloned into the pBK-CMV vector. The MICs of FQs were determined by microdilution. Mutant prevention concentration and frequency of mutants were evaluated. Bacterial fitness was analysed using DeltalacZ system competition assays using in vitro and in vivo models. RESULTS: The relationships between the number of resistance mutations and bacterial fitness were complex. With specific combinations of resistance mechanisms the addition of a new resistance mutation was shown to improve bacterial fitness. qnrA1 caused a decrease in fitness (7%-21%) while qnrS1 caused an increase in fitness (9%-21%) when combined with chromosomal mutations. We identified susceptible triple mutants in which the acquisition of a fourth resistance mutation significantly increased fitness and at the same time reached the clinical resistance level (the acquisition of qnrS1 in a S83L + D87N + DeltamarR genetic background). A strong correlation with the production of reactive oxygen species, as well as changes in susceptibility, was observed following treatment with ciprofloxacin. CONCLUSIONS: Our data indicate that there may be critical stages (depending on the genotype) in resistance development, including chromosomal- and plasmid-mediated mechanisms, at which some low-fitness mutants below the resistance breakpoint are able to evolve clinical resistance with just one or two mutations, and show increased fitness. PMID- 25139838 TI - MacABCsm, an ABC-type tripartite efflux pump of Stenotrophomonas maltophilia involved in drug resistance, oxidative and envelope stress tolerances and biofilm formation. AB - OBJECTIVES: To characterize a five gene cluster, macRS-macABCsm, in Stenotrophomonas maltophilia. METHODS: The presence of macABCsm operon was verified by RT-PCR. The substrate spectrum of the MacABCsm efflux pump was investigated by mutant construction and susceptibility testing. The physiological role of MacABCsm was assessed by comparing the growth of wild-type and macABCsm mutant under different stresses. To examine the regulatory role of the two component regulatory system (TCS) macRS in the expression of macABCsm operon, mutant construction, quantitative RT-PCR and susceptibility testing were employed. RESULTS: macAsm, macBsm and macCsm genes formed a three-membered operon. The MacABCsm efflux pump extruded macrolides, aminoglycosides and polymyxins and contributed to oxidative and envelope stress tolerances and biofilm formation. Inactivation of macRS TCS hardly influenced the expression of macABCsm operon and the antimicrobial susceptibility. CONCLUSIONS: The MacABCsm pump has physiological roles in protecting S. maltophilia from the attack of oxidative and envelope stresses and in biofilm formation, which may be the reason why it can be constitutively expressed in the absence of antibiotics and is highly conserved in S. maltophilia isolates isolated from different environmental niches. However, the constitutive expression of macABCsm contributes to the intrinsic resistance of S. maltophilia to macrolides, aminoglycosides and polymyxins. PMID- 25139839 TI - Prophylactic treatment with a novel bioadhesive gel formulation containing aciclovir and tenofovir protects from HSV-2 infection. AB - OBJECTIVES: Over-the-counter access to an inexpensive, effective topical microbicide could reduce the transmission of HIV and would increase women's control over their health and eliminate the need to obtain their partners' consent for prophylaxis. Chronic infection with herpes simplex virus 2 (HSV-2), also known as human herpes virus 2, has been shown to facilitate HIV infection and speed the progression to immunodeficiency disease. Our objective is to develop a drug formulation that protects against both HSV-2 and HIV infection and adheres to the vaginal surface with extended residence time. METHODS: We developed a formulation using two approved antiviral active pharmaceutical ingredients, aciclovir and tenofovir, in a novel bioadhesive vaginal delivery platform (designated SR-2P) composed of two polymers, poloxamer 407 NF (Pluronic((r)) F-127) and polycarbophil USP (Noveon((r)) AA-1). The efficacy of the formulation to protect from HSV-2 infection was tested in vitro and in vivo. In addition to its efficacy, it is essential for a successful microbicide to be non-irritating to the vaginal mucosa. We therefore tested our SR-2P platform gel in the FDA gold-standard microbicide safety model in rabbits and also in a rat vaginal irritation model. RESULTS: Our studies indicated that SR-2P containing 1% aciclovir and 5% tenofovir protects (i) Vero cells from HSV-2 infection in vitro and (ii) mice from HSV-2 infection in vivo. Our results further demonstrated that SR-2P was not irritating in either vaginal irritation model. CONCLUSIONS: We conclude that SR-2P containing aciclovir and tenofovir may be a suitable candidate microbicide to protect humans from vaginal HSV-2 infection. PMID- 25139840 TI - Pharmacokinetics of caspofungin in ICU patients. AB - OBJECTIVES: Caspofungin is used for treatment of invasive fungal infections. As the pharmacokinetics (PK) of antimicrobial agents in critically ill patients can be highly variable, we set out to explore caspofungin PK in ICU patients. METHODS: ICU patients receiving caspofungin were eligible. Patients received a loading dose of 70 mg followed by 50 mg daily (70 mg if body weight >80 kg); they were evaluable upon completion of the first PK curve at day 3. Additionally, daily trough samples were taken and a second PK curve was recorded at day 7. PK analysis was performed using a standard two-stage approach. RESULTS: Twenty-one patients were evaluable. Median (range) age and body weight were 71 (45-80) years and 75 (50-99) kg. PK sampling on day 3 (n = 21) resulted in the following median (IQR) parameters: AUC0-24 88.7 (72.2-97.5) mg.h/L; Cmin 2.15 (1.40-2.48) mg/L; Cmax 7.51 (6.05-8.17) mg/L; V 7.72 (6.12-9.01) L; and CL 0.57 (0.54-0.77) L/h. PK sampling on day 7 (n = 13) resulted in AUC0-24 107.2 (90.4-125.3) mg.h/L, Cmin 2.55 (1.82-3.08) mg/L, Cmax 8.65 (7.16-9.34) mg/L, V 7.03 (5.51-7.73) L and CL 0.54 (0.44-0.60) L/h. We did not identify any covariates significantly affecting caspofungin PK in ICU patients (e.g. body weight, albumin, liver function). Caspofungin was well tolerated and no unexpected side effects were observed. CONCLUSIONS: Caspofungin PK in ICU patients showed limited intraindividual and moderate interindividual variability, and caspofungin was well tolerated. A standard two-stage approach did not reveal significant covariates. Our study showed similar caspofungin PK parameters in ICU patients compared with non critically ill patients. PMID- 25139841 TI - Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab: a systematic review and meta-analysis. AB - BACKGROUND: We performed a systematic review and meta-analysis of the correlation between cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab. PATIENTS AND METHODS: Eligible studies included phase I, II and III trials of patients with solid tumors on cetuximab; describing events of skin rash and correlating skin rash with overall survival (OS), progression free survival (PFS) and/or overall response rate (ORR). RESULTS: Our search strategy yielded 409 potentially relevant citations on CETUXIMAB from Pubmed/Medline, CENTRAL Cochrane registry and ASCO meeting library. After exclusion of ineligible studies, a total of 13 clinical trials were considered eligible for the meta analysis, including 4 phase III trials, 8 phase II trials and one phase I trial. The occurrence of cetuximab-induced rash in patients was highly associated with improvements in PFS (HR=0.74; 95% CI: 0.63-0.86, P<0.0002), OS (HR=0.60; 95% CI: 0.47-0.76, P<0.0001), and ORR (RR=1.51, 95% CI: 1.26-1.81, P<0.00001), as compared to patients without rash. Exploratory subgroup analysis showed no effect of tumor types on the RR of ORR. CONCLUSIONS: Our meta-analysis has demonstrated that cetuximab-induced rash is associated with a significantly improved OS, PFS and ORR. Cetuximab-induced skin rash may represent a prognostic factor in patients with advanced solid tumors. PMID- 25139842 TI - 1-Acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles: exhibiting anticancer activity through intracellular ROS scavenging and the mitochondria-dependent death pathway. AB - A series of 17 analogs of 1-acetyl-4,5-dihydro(1H)pyrazoles (JP-1 to JP-17) bearing two aromatic rings at positions 3 and 5, either of which ought to be heterocyclic, were synthesized and evaluated for their anti-proliferative potential against breast cancer (MCF-7 and T-47D) and lung cancer (H-460 and A 549) cell lines for the first time. JP-1-7, -10, -11, -14, and -15 were observed to exhibit significant anti-proliferative activity against MCF-7 cells. Some notions about structure-activity relationships are reported. The investigated compounds were found to lower the intracellular reactive oxygen species in the H2 DCFDA assay and also caused mitochondria-dependent cell death in the MCF-7 cell line, indicating a plausible mechanism of their anticancer effect. PMID- 25139843 TI - Carbapenems and piperacillin/tazobactam for the treatment of bacteremia caused by extended-spectrum beta-lactamase-producing Proteus mirabilis. AB - This study was intended to delineate the role of carbapenems and piperacillin/tazobactam in treating bacteremia caused by extended-spectrum beta lactamase (ESBL)-producing Proteus mirabilis. We performed a multicenter and retrospective study of the patients with ESBL-producing P. mirabilis bacteremia. The outcomes of the patients treated by piperacillin/tazobactam or a carbapenem for at least 48 hours and the MICs of the prescribed drugs for these isolates were analyzed. Forty-seven patients with available clinical data were included. The overall 30-day mortality rate was 29.8%. All available isolates (n = 44) were susceptible to ertapenem, meropenem, and doripenem, and 95.6% were susceptible to piperacillin/tazobactam; however, only 11.4% of the isolates were susceptible to imipenem. Among the 3 patients infected with isolates exhibiting non susceptibility to imipenem (MIC >=2 mg/L) who were treated with imipenem, none died within 28 days. The 30-day (14.3% versus 23.1%, P = 0.65) or in-hospital (19.1% versus 30.8%, P = 0.68) mortality rate of 21 patients treated by a carbapenem was lower than that of 13 treated by piperacillin/tazobactam. However, among those treated by piperacillin/tazobactam, the mortality rate of those infected by the isolates with lower piperacillin/tazobactam MICs (<=0.5/4 mg/L) was lower than that of the isolates with MICs of >=1/4 mg/L (0%, 0/7 versus 60%, 3/5; P = 0.045). ESBL-producing P. mirabilis bacteremia is associated with significant mortality, and carbapenem therapy could be regarded as the drugs of choice. The role of piperacillin/tazobactam, especially for the infections due to the isolates with an MIC <=0.5/4 mg/L, warrants more clinical studies. PMID- 25139844 TI - Direct identification of bacteria from positive BacT/ALERT blood culture bottles using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. AB - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is a fast and robust method for the identification of bacteria. In this study, we evaluate the performance of a laboratory-developed lysis method (LDT) for the rapid identification of bacteria from positive BacT/ALERT blood culture bottles. Of the 168 positive bottles tested, 159 were monomicrobial, the majority of which were Gram-positive organisms (61.0% versus 39.0%). Using a cut-off score of >=1.7, 80.4% of the organisms were correctly identified to the species level, and the identification rate of Gram-negative organisms (90.3%) was found to be significantly greater than that of Gram-positive organisms (78.4%). The simplicity and cost-effectiveness of the LDT enable it to be fully integrated into the routine workflow of the clinical microbiology laboratory, allowing for rapid identification of Gram-positive and Gram-negative bacteria within an hour of blood culture positivity. PMID- 25139845 TI - Structure and transfer of the vanA cluster in vanA-positive, vancomycin susceptible Enterococcus faecium, and its revertant mutant. AB - Of 18 vanA-positive vancomycin-susceptible Enterococcus faecium isolates, vanRS in the vanA cluster was detected in all isolates, while vanHAX was detected in only 2 isolates. Following exposure to glycopeptides, 22.2% of vancomycin susceptible E. faecium (VSE) converted into vancomycin-resistant E. faecium. The vanA cluster of the revertant mutant was transferred to the VSE isolates. PMID- 25139846 TI - Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412. AB - Mastocytosis are myeloproliferative neoplasms commonly related to gain-of function mutations involving the tyrosine kinase domain of KIT. We herein report a case of familial systemic mastocytosis with the rare KIT K509I germ line mutation affecting two family members: mother and daughter. In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. However, imatinib was more effective in inducing apoptosis of neoplastic mast cells. Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment, suggesting that it may be an effective front line therapy for patients harboring KIT K509I mutation. PMID- 25139847 TI - Results of allogeneic stem cell transplantation in the Spanish MDS registry: prognostic factors for low risk patients. AB - Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics. PMID- 25139848 TI - A paradigm for cybernetics, regulatory circuits and ultra-stability in cancer biology and treatment. PMID- 25139849 TI - Leveraging Administrative Data for Program Evaluations: A Method for Linking Data Sets Without Unique Identifiers. AB - In community-based wellness programs, Social Security Numbers (SSNs) are rarely collected to encourage participation and protect participant privacy. One measure of program effectiveness includes changes in health care utilization. For the 65 and over population, health care utilization is captured in Medicare administrative claims data. Therefore, methods as described in this article for linking participant information to administrative data are useful for program evaluations where unique identifiers such as SSN are not available. Following fuzzy matching methodologies, participant information from the National Study of the Chronic Disease Self-Management Program was linked to Medicare administrative data. Linking variables included participant name, date of birth, gender, address, and ZIP code. Seventy-eight percent of participants were linked to their Medicare claims data. Linking program participant information to Medicare administrative data where unique identifiers are not available provides researchers with the ability to leverage claims data to better understand program effects. PMID- 25139850 TI - Okadaic acid blocks the effects of 5-aza-2-deoxycytidine on consolidation, acquisition and retrieval of morphine-induced place preference in rats. AB - Recent studies indicated that epigenetic modification, especially DNA methylation, play an important role in the persistence of addiction-related memory. 5-aza-2-deoxycytidine (5-aza), an inhibitor of DNA methyltransferases, was approved for clinical treatment. However, it is not clear whether 5-aza is involved in opiate addiction. In this study, using the morphine-induced conditioned place preference (mCPP) model in rats, we injected 5-aza into hippocampus (CA1) and prelimbic cortex (PL), and tested the behavioral consequences at various stages of consolidation, acquisition and retrieval. Moreover, to test whether protein phosphatase regulates the effects of 5-aza, protein phosphatase (PP) 1/2A inhibitor okadaic acid (OA) was infused before 5 aza injection. We found that 5-aza injection into CA1 but not into PL significantly attenuated the consolidation and acquisition of mCPP, however, the inhibition of DNA methylation in PL but not in CA1 enhanced the retrieval of mCPP. All these behavioral effects were absent when OA was infused before 5-aza injection. These findings suggest that 5-aza interfere opiate-related memory, and protein phosphatase plays an important role in this process. PMID- 25139851 TI - Semaphorin signalling during development. AB - Semaphorins are secreted and membrane-associated proteins that regulate many different developmental processes, including neural circuit assembly, bone formation and angiogenesis. Trans and cis interactions between semaphorins and their multimeric receptors trigger intracellular signal transduction networks that regulate cytoskeletal dynamics and influence cell shape, differentiation, motility and survival. Here and in the accompanying poster we provide an overview of the molecular biology of semaphorin signalling within the context of specific cell and developmental processes, highlighting the mechanisms that act to fine tune, diversify and spatiotemporally control the effects of semaphorins. PMID- 25139852 TI - Coordinating cell polarity: heading in the right direction? AB - A diverse group of researchers working on both plant and animal systems met at a Company of Biologists workshop to discuss 'Coordinating Cell Polarity'. The meeting included considerable free discussion as well as presentations exploring the ways that groups of cells in these various systems achieve coordinated cell polarity. Here, we discuss commonalities, differences and themes that emerged from these sessions that will serve to inform ongoing studies. PMID- 25139853 TI - The cellular basis of tissue separation. AB - The subdivision of the embryo into physically distinct regions is one of the most fundamental processes in development. General hypotheses for tissue separation based on differential adhesion or tension have been proposed in the past, but with little experimental support. During the last decade, the field has experienced a strong revival, largely driven by renewed interest in biophysical modeling of development. Here, I will discuss the various models of boundary formation and summarize recent studies that have shifted our understanding of the process from the simple juxtaposition of global tissue properties to the characterization of local cellular reactions. Current evidence favors a model whereby separation is controlled by cell surface cues, which, upon cell-cell contact, generate acute changes in cytoskeletal and adhesive properties to inhibit cell mixing, and whereby the integration of multiple local cues may dictate both the global morphogenetic properties of a tissue and its separation from adjacent cell populations. PMID- 25139854 TI - Runx1 is required for progression of CD41+ embryonic precursors into HSCs but not prior to this. AB - Haematopoiesis in adult animals is maintained by haematopoietic stem cells (HSCs), which self-renew and can give rise to all blood cell lineages. The AGM region is an important intra-embryonic site of HSC development and a wealth of evidence indicates that HSCs emerge from the endothelium of the embryonic dorsal aorta and extra-embryonic large arteries. This, however, is a stepwise process that occurs through sequential upregulation of CD41 and CD45 followed by emergence of fully functional definitive HSCs. Although largely dispensable at later stages, the Runx1 transcription factor is crucially important during developmental maturation of HSCs; however, exact points of crucial involvement of Runx1 in this multi-step developmental maturation process remain unclear. Here, we have investigated requirements for Runx1 using a conditional reversible knockout strategy. We report that Runx1 deficiency does not preclude formation of VE-cad+CD45-CD41+ cells, which are phenotypically equivalent to precursors of definitive HSCs (pre-HSC Type I) but blocks transition to the subsequent CD45+ stage (pre-HSC Type II). These data emphasise that developmental progression of HSCs during a very short period of time is regulated by precise stage-specific molecular mechanisms. PMID- 25139855 TI - Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly. AB - Lens epithelial cells and early lens fiber cells contain the typical complement of intracellular organelles. However, as lens fiber cells mature they must destroy their organelles, including nuclei, in a process that has remained enigmatic for over a century, but which is crucial for the formation of the organelle-free zone in the center of the lens that assures clarity and function to transmit light. Nuclear degradation in lens fiber cells requires the nuclease DNase IIbeta (DLAD) but the mechanism by which DLAD gains access to nuclear DNA remains unknown. In eukaryotic cells, cyclin-dependent kinase 1 (CDK1), in combination with either activator cyclins A or B, stimulates mitotic entry, in part, by phosphorylating the nuclear lamin proteins leading to the disassembly of the nuclear lamina and subsequent nuclear envelope breakdown. Although most post mitotic cells lack CDK1 and cyclins, lens fiber cells maintain these proteins. Here, we show that loss of CDK1 from the lens inhibited the phosphorylation of nuclear lamins A and C, prevented the entry of DLAD into the nucleus, and resulted in abnormal retention of nuclei. In the presence of CDK1, a single focus of the phosphonuclear mitotic apparatus is observed, but it is not focused in CDK1-deficient lenses. CDK1 deficiency inhibited mitosis, but did not prevent DNA replication, resulting in an overall reduction of lens epithelial cells, with the remaining cells possessing an abnormally large nucleus. These observations suggest that CDK1-dependent phosphorylations required for the initiation of nuclear membrane disassembly during mitosis are adapted for removal of nuclei during fiber cell differentiation. PMID- 25139856 TI - Heterotrimeric Go protein links Wnt-Frizzled signaling with ankyrins to regulate the neuronal microtubule cytoskeleton. AB - Drosophila neuromuscular junctions (NMJs) represent a powerful model system with which to study glutamatergic synapse formation and remodeling. Several proteins have been implicated in these processes, including components of canonical Wingless (Drosophila Wnt1) signaling and the giant isoforms of the membrane cytoskeleton linker Ankyrin 2, but possible interconnections and cooperation between these proteins were unknown. Here, we demonstrate that the heterotrimeric G protein Go functions as a transducer of Wingless-Frizzled 2 signaling in the synapse. We identify Ankyrin 2 as a target of Go signaling required for NMJ formation. Moreover, the Go-ankyrin interaction is conserved in the mammalian neurite outgrowth pathway. Without ankyrins, a major switch in the Go-induced neuronal cytoskeleton program is observed, from microtubule-dependent neurite outgrowth to actin-dependent lamellopodial induction. These findings describe a novel mechanism regulating the microtubule cytoskeleton in the nervous system. Our work in Drosophila and mammalian cells suggests that this mechanism might be generally applicable in nervous system development and function. PMID- 25139857 TI - Systematic discovery of novel ciliary genes through functional genomics in the zebrafish. AB - Cilia are microtubule-based hair-like organelles that play many important roles in development and physiology, and are implicated in a rapidly expanding spectrum of human diseases, collectively termed ciliopathies. Primary ciliary dyskinesia (PCD), one of the most prevalent of ciliopathies, arises from abnormalities in the differentiation or motility of the motile cilia. Despite their biomedical importance, a methodical functional screen for ciliary genes has not been carried out in any vertebrate at the organismal level. We sought to systematically discover novel motile cilia genes by identifying the genes induced by Foxj1, a winged-helix transcription factor that has an evolutionarily conserved role as the master regulator of motile cilia biogenesis. Unexpectedly, we find that the majority of the Foxj1-induced genes have not been associated with cilia before. To characterize these novel putative ciliary genes, we subjected 50 randomly selected candidates to a systematic functional phenotypic screen in zebrafish embryos. Remarkably, we find that over 60% are required for ciliary differentiation or function, whereas 30% of the proteins encoded by these genes localize to motile cilia. We also show that these genes regulate the proper differentiation and beating of motile cilia. This collection of Foxj1-induced genes will be invaluable for furthering our understanding of ciliary biology, and in the identification of new mutations underlying ciliary disorders in humans. PMID- 25139858 TI - Nephric duct insertion requires EphA4/EphA7 signaling from the pericloacal mesenchyme. AB - The vesico-ureteric junction (VUJ) forms through a complex developmental program that connects the primordium of the upper urinary tract [the nephric duct (ND)] with that of the lower urinary tract (the cloaca). The signals that orchestrate the various tissue interactions in this program are poorly understood. Here, we show that two members of the EphA subfamily of receptor tyrosine kinases, EphA4 and EphA7, are specifically expressed in the mesenchyme surrounding the caudal ND and the cloaca, and that Epha4(-/-);Epha7(+/-) and Epha4(-/-);Epha7(-/-) (DKO) mice display distal ureter malformations including ureterocele, blind and ectopically ending ureters with associated hydroureter, megaureter and hydronephrosis. We trace these defects to a late or absent fusion of the ND with the cloaca. In DKO embryos, the ND extends normally and approaches the cloaca but the tip subsequently looses its integrity. Expression of Gata3 and Lhx1 and their downstream target Ret is severely reduced in the caudal ND. Conditional deletion of ephrin B2 from the ND largely phenocopies these changes, suggesting that EphA4/EphA7 from the pericloacal mesenchyme signal via ephrin B2 to mediate ND insertion. Disturbed activity of this signaling module may entail defects of the VUJ, which are frequent in the spectrum of congenital anomalies of the kidney and the urinary tract (CAKUT) in human newborns. PMID- 25139861 TI - Associations between active commuting, body fat, and body mass index: population based, cross sectional study in the United Kingdom. AB - OBJECTIVE: To determine if promotion of active modes of travel is an effective strategy for obesity prevention by assessing whether active commuting (walking or cycling for all or part of the journey to work) is independently associated with objectively assessed biological markers of obesity. DESIGN: Cross sectional study of data from the wave 2 Health Assessment subsample of Understanding Society, the UK Household Longitudinal Study (UKHLS). The exposure of interest, commuting mode, was self reported and categorised as three categories: private transport, public transport, and active transport. PARTICIPANTS: The analytic samples (7534 for body mass index (BMI) analysis, 7424 for percentage body fat analysis) were drawn from the representative subsample of wave 2 respondents of UKHLS who provided health assessment data (n = 15,777). MAIN OUTCOME MEASURES: Body mass index (weight (kg)/height (m)(2)); percentage body fat (measured by electrical impedance). RESULTS: Results from multivariate linear regression analyses suggest that, compared with using private transport, commuting by public or active transport modes was significantly and independently predictive of lower BMI for both men and women. In fully adjusted models, men who commuted via public or active modes had BMI scores 1.10 (95% CI 0.53 to 1.67) and 0.97 (0.40 to 1.55) points lower, respectively, than those who used private transport. Women who commuted via public or active modes had BMI scores 0.72 (0.06 to 1.37) and 0.87 (0.36 to 0.87) points lower, respectively, than those using private transport. Results for percentage body fat were similar in terms of magnitude, significance, and direction of effects. CONCLUSIONS: Men and women who commuted to work by active and public modes of transport had significantly lower BMI and percentage body fat than their counterparts who used private transport. These associations were not attenuated by adjustment for a range of hypothesised confounding factors. PMID- 25139862 TI - Isolated talonavicular fusion with tension band for Muller-Weiss syndrome. AB - BACKGROUND: There are still controversies with regard to the operative treatment in advanced Muller-Weiss syndrome (MWS), where the navicular undergoes avascular necrosis and the talonavicular (TN) joint becomes arthritic. Most authors advocate extended fusion, sacrificing hindfoot mobility. To restore TN alignment and to achieve stable fixation, we developed a new isolated TN fusion technique applying the principles of a static tension band. The aim of the present study was to report the midterm results of a preliminary series of patients and their clinical and radiographic outcomes. METHODS: Ten feet (10 patients; 8 females, 2 males; age 63 +/- 16.7 [range, 34-83] years) with advanced deformity of MWS (3 Maceira's stage III and 7 stage IV) were treated with isolated TN arthrodesis using the tension band technique. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score was used to evaluate the functional outcome. Standard angles were measured to determine the amount of correction achieved through the operative treatment. The minimum follow-up was 24 (range, 24-43) months. RESULTS: Trabeculation was seen to cross the fusion site on radiographs in 8 patients after 2 and in 1 patient after 3 months. One case needed revision after 13 months due to implant failure; after additional screw fixation, bony healing was achieved 2 months later. At last follow-up, all cases described a high level of satisfaction. Postoperatively, the AOFAS score improved from 33 (range, 18-48) to 88.3 (range, 79-100) (P < .0001) points, the AP talocalcaneal angle increased from 14.2 (range, 1-22) to 22.7 (range, 12-30) degrees (P = .0007), and the calcaneal pitch increased from 10.3 (range, 3-22) to 14.7 (range, 8-22) degrees (P = .0006). CONCLUSION: The static tension band technique is a new, promising technique to treat MWS patients, providing stability against the counteracting deforming forces. Therefore, we consider this technique as our treatment of choice in patients with stage III and stage IV MWS. LEVEL OF EVIDENCE: Level IV, prospective case series. PMID- 25139863 TI - Gestalt grouping via closure degrades suprathreshold depth percepts. AB - It is well known that the perception of depth is susceptible to changes in configuration. For example, stereoscopic precision for a pair of vertical lines can be dramatically reduced when these lines are connected to form a closed object. Here, we extend this paradigm to suprathreshold estimates of perceived depth. Using a touch-sensor, observers made quantitative estimates of depth between a vertical line pair presented in isolation or as edges of a closed rectangular object with different figural interpretations. First, we show that the amount of depth estimated within a closed rectangular object is consistently reduced relative to the vertical edges presented in isolation or when they form the edges of two segmented objects. We then demonstrate that the reduction in perceived depth for closed objects is modulated by manipulations that influence perceived closure of the central figure. Depth percepts were most disrupted when the horizontal connectors and vertical lines matched in color. Perceived depth increased slightly when the connectors had opposite contrast polarity, but increased dramatically when flankers were added. Thus, as grouping cues were added to counter the interpretation of a closed object, the depth degradation effect was systematically eliminated. The configurations tested here rule out explanations based on early, local interactions such as inhibition or cue conflict; instead, our results provide strong evidence of the impact of Gestalt grouping, via closure, on depth magnitude percepts from stereopsis. PMID- 25139864 TI - Human vision is attuned to the diffuseness of natural light. AB - All images are highly ambiguous, and to perceive 3-D scenes, the human visual system relies on assumptions about what lighting conditions are most probable. Here we show that human observers' assumptions about lighting diffuseness are well matched to the diffuseness of lighting in real-world scenes. We use a novel multidirectional photometer to measure lighting in hundreds of environments, and we find that the diffuseness of natural lighting falls in the same range as previous psychophysical estimates of the visual system's assumptions about diffuseness. We also find that natural lighting is typically directional enough to override human observers' assumption that light comes from above. Furthermore, we find that, although human performance on some tasks is worse in diffuse light, this can be largely accounted for by intrinsic task difficulty. These findings suggest that human vision is attuned to the diffuseness levels of natural lighting conditions. PMID- 25139868 TI - Healthier commuting. PMID- 25139869 TI - Universal cures for idiosyncratic illnesses: A genealogy of therapeutic reasoning in the mental health field. AB - Over the past decades, there has been a significant increase in prescriptions of psychotropic drugs for mental disorders. So far, most of the explanations of the phenomenon have focused on the process of medicalization, but little attention has been cast towards physicians' day-to-day clinical reasoning, and the way it affects therapeutic decision-making. This article addresses the complex relationship between aetiology, diagnosis and drug treatment by examining the style of reasoning underlying prescribing practices through an historical lens. A genealogy of contemporary prescribing practices is proposed, that draws significant comparisons between 19th-century medicine and modern psychiatry. Tensions between specific, standardized cures and specific, idiosyncratic patients have been historically at play in clinical reasoning - and still are today. This inquiry into the epistemological foundations of contemporary drug prescription reveals an underlying search for scientific legitimacy. PMID- 25139870 TI - Education as networking: Rethinking the success of the harm reduction policy of Taiwan. AB - The harm reduction policy of Taiwan has been considered a success. However, the HIV incidence among injection drug users declined before the nationwide needle and syringe program and drug substitution treatments were implemented. Thus, other factors in the policy might have contributed to its success. Some authors have suggested that education may have played a pivotal part. In this research, the purported significance of education in the success of the policy is conceptualized by reviewing the studies on harm reduction in Taiwan and reflecting upon my own fieldwork. Moreover, relevant literature is used as reference to reformulate this notion of education. This article shows that harm reduction education may be conducted in numerous forms, most of which are non formal, improvisational, and contingent. Non-governmental organizations may play a role, but more actors, strategies, infrastructures, and interactions should be considered. This article draws from actor-network theory and refines the current thesis that attributes the policy success to education by utilizing three reflections, namely, appreciating materiality and spatiality, recognizing covert actors in the networking, and treating education as an outcome rather than a means. In conclusion, looking at education as a form of networking offers theoretical insight that increases understanding of its participants, mechanisms, processes, and permutations. PMID- 25139871 TI - Facile fabrication of a well-ordered porous Cu-doped SnO2 thin film for H2S sensing. AB - Well-ordered Cu-doped and undoped SnO2 porous thin films with large specific surface areas have been fabricated on a desired substrate using a self-assembled soft template combined with simple physical cosputtering deposition. The Cu-doped SnO2 porous film gas sensor shows a significant enhancement in its sensing performance, including a high sensitivity, selectivity, and a fast response and recovery time. The sensitivity of the Cu-doped SnO2 porous sensor is 1 order of magnitude higher than that of the undoped SnO2 sensor, with average response and recovery times to 100 ppm of H2S of ~ 10.1 and ~ 42.4 s, respectively, at the optimal operating temperature of 180 degrees C. The well-defined porous sensors fabricated by the method also exhibit high reproducibility because of the accurately controlled fabrication process. The facile process can be easily extended to the fabrication of other semiconductor oxide gas sensors with easy doping and multilayer porous nanostructure for practical sensing applications. PMID- 25139872 TI - Integrating community health workers into a patient-centered medical home to support disease self-management among Vietnamese Americans: lessons learned. AB - There is evidence that patient-centered medical homes (PCMHs) and community health workers (CHWs) improve chronic disease management. There are few models for integrating CHWs into PCMHs in order to enhance disease self-management support among diverse populations. In this article, we describe how a community based nonprofit agency, a PCMH, and academic partners collaborated to develop and implement the Patient Resource and Education Program (PREP). We employed CHWs as PCMH care team members to provide health education and support to Vietnamese American patients with uncontrolled diabetes and/or hypertension. We began by conducting focus groups to assess patient knowledge, desire for support, and availability of community resources. Based on findings, we developed PREP with CHW guidance on cultural tailoring of educational materials and methods. CHWs received training in core competencies related to self-management support principles and conducted the 4-month intervention for PCMH patients. Throughout the program, we conducted process evaluation through structured team meetings and patient satisfaction surveys. We describe successes and challenges associated with PREP delivery including patient recruitment, structuring/documenting visits, and establishing effective care team integration, work flow, and communication. Strategies for mitigating these issues are presented, and we make recommendations for other PCMHs seeking to integrate CHWs into care teams. PMID- 25139873 TI - Early deterioration after thrombolysis plus aspirin in acute stroke: a post hoc analysis of the Antiplatelet Therapy in Combination with Recombinant t-PA Thrombolysis in Ischemic Stroke trial. AB - BACKGROUND AND PURPOSE: Aspirin early after intravenous thrombolysis in acute ischemic stroke increases the risk of symptomatic intracranial hemorrhage (SICH), without influencing functional outcome at 3 months. The effect of aspirin on early neurological deterioration (END) was explored as a post hoc analysis of the randomized Antiplatelet Therapy in Combination With Recombinant t-PA Thrombolysis in Ischemic Stroke (ARTIS) trial. METHODS: END, defined as a >=4 points National Institutes of Health Stroke Scale worsening <=24 hours after intravenous thrombolysis, was categorized into SICH (ENDSICH) and cerebral ischemia (ENDCI). Multinomial logistic regression was used to assess the effect of aspirin on END. RESULTS: Of the 640 patients, 31 patients (4.8%) experienced END (14 ENDSICH, 17 ENDCI). Aspirin increased the risk of ENDSICH (odds ratio, 3.73; 95% confidence interval, 1.03-13.49) but not of ENDCI (odds ratio, 1.14; 95% confidence interval, 0.44-3.00). After adjustment for other explanatory variables, the association between aspirin and ENDSICH remained significant. CONCLUSIONS: In this trial, there is no evidence of an early antithrombotic effect from the addition of aspirin to intravenous thrombolysis in acute ischemic stroke. PMID- 25139874 TI - Association of interleukin-6 with the progression of carotid atherosclerosis: a 9 year follow-up study. AB - BACKGROUND AND PURPOSE: Limited information is available on the long-term effects of interleukin-6 (IL-6) on systemic atherosclerosis. The purpose of the present study was to clarify the relationship between chronic elevation of IL-6 and the long-term progression of carotid atherosclerosis. METHODS: We prospectively evaluated 210 patients with >=1 vascular risk factors for 9.0+/-1.0 years. Carotid mean-maximal intima-media thickness (mmIMT), the serum high-sensitivity C reactive protein (hs-CRP) level, and the serum IL-6 level were measured at baseline and every 3 years. The associations between the progression of mmIMT and the long-term average levels of hs-CRP and IL-6 were analyzed. RESULTS: Carotid mmIMT increased throughout the study period (0.031+/-0.026 mm/y). Baseline mmIMT was significantly associated with baseline hs-CRP (P=0.002) and baseline IL-6 (P<0.001) levels. Progression of mmIMT was positively correlated with average hs CRP (P=0.001) and average IL-6 (P<0.001) levels. When adjusted for age, sex, traditional risk factors, and baseline mmIMT, mmIMT progression remained significantly associated only with the average IL-6 level (standardized beta=0.17; P=0.02), but not with the average hs-CRP level (standardized beta=0.10; P=0.18). CONCLUSIONS: Chronic elevation of serum IL-6 was associated with the progression of atherosclerosis in patients with vascular risk factors. IL-6 could be used as a quantitative marker and a potential therapeutic target for accelerated atherosclerosis. PMID- 25139875 TI - Intervention of death-associated protein kinase 1-p53 interaction exerts the therapeutic effects against stroke. AB - BACKGROUND AND PURPOSE: Death-associated protein kinase 1 (DAPK1) interacts with the tumor suppressor gene p53 via a direct binding of a death domain of DAPK1 to a DNA-binding motif (DM) of p53 (p53DM) and converges multiple cell death pathways in stroke. The goals of this study are to determine whether disruption of DAPK1-p53 interaction is therapeutically effective against stroke. METHODS: We synthesized a membrane-permeable p53DM peptide (Tat-p53DM) and tested the therapeutic effects of Tat-p53DM in a mouse model with stroke. RESULTS: We showed that Tat-p53DM blocked DAPK1-p53 interaction in brain cells in vivo. When administered 6 hours after stroke onset in adult male mice, Tat-p53DM was still therapeutically effective against brain damages and improved neurological functions. CONCLUSIONS: DAPK1-p53 interaction is a preferred target for therapeutic intervention of stroke. PMID- 25139876 TI - Follistatin-like 1 attenuates apoptosis via disco-interacting protein 2 homolog A/Akt pathway after middle cerebral artery occlusion in rats. AB - BACKGROUND AND PURPOSE: Follistatin-like 1 (FSTL1), an extracellular glycoprotein, has been reported to decrease apoptosis in ischemic cardiac diseases, but its effect in ischemic stroke has not been examined. We hypothesized that recombinant FSTL1 attenuates neuronal apoptosis through its receptor disco-interacting protein 2 homolog A (DIP2A) and the Akt pathway after middle cerebral artery occlusion (MCAO) in rats. METHODS: One hundred forty male Sprague-Dawley rats were subjected to 2 hours of MCAO followed by reperfusion. In a subset of animals, the time course and location of FSTL1 and DIP2A were detected by Western blot and immunofluorescence double staining. Another set of animals were intracerebroventricularly given either recombinant FSTL1 1 hour after reperfusion or FSTL1-small interfering RNA (siRNA) 48 hours before reperfusion. Additionally, DIP2A was knockdown by siRNA in some animals. Infarction volume and neurological deficits were measured, and the expression of FSTL1, DIP2A, phosphorylated Akt, cleaved caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labeling were quantified using Western blot. RESULTS: The expression of FSTL1 and DIP2A was increased in neurons and peaked 24 hours after MCAO. Recombinant FSTL1 reduced brain infarction and improved neurological deficits 24 and 72 hours after MCAO via activation of its receptor DIP2A and downstream phosphorylation of Akt. These effects were reversed by DIP2A-siRNA and FSTL1-siRNA. CONCLUSIONS: Recombinant FSTL1 decreases neuronal apoptosis and improves neurological deficits through phosphorylation of Akt by activation of its receptor DIP2A after MCAO in rats. Thus, FSTL1 may have potentials as a treatment for patients with ischemic stroke. PMID- 25139877 TI - Impact of living alone on the care and outcomes of patients with acute stroke. AB - BACKGROUND AND PURPOSE: Outcomes among patients living alone at stroke onset could be directly affected by reduced access to acute therapies or indirectly through the effects of social isolation. We examined the associations between living alone at home and acute stroke care and outcomes in the Registry of the Canadian Stroke Network. METHODS: Between 2003 and 2008, 10 048 patients with acute stroke (87% ischemic, 13% hemorrhagic) who were living at home were admitted to 11 Ontario hospitals. Outcomes included arrival<=2.5 hours of onset, thrombolytic treatment, discharge home, 30-day and 1-year mortality, and 1-year readmission. The effects of living alone versus living with others were determined using multivariable logistic regression. RESULTS: Overall, 22.8% (n=2288) of patients were living alone at home before stroke. Subjects living alone were significantly older (mean, 74.6 versus 71.5 years), more likely to be women (61.5% versus 41.4%), widowed (53.7% versus 12.3%), or single (21.5% versus 3.8%). Patients living alone were less likely to arrive within 2.5 hours (28.3% versus 40.0%; adjusted odds ratio, 0.54; 95% confidence interval, 0.48-0.60), to receive thrombolysis (8.0% versus 14.0%; adjusted odds ratio, 0.52; 95% confidence interval, 0.43-0.63), or to be discharged home (46.0% versus 54.7%; adjusted odds ratio, 0.65; 95% confidence interval, 0.58-0.73). There were no significant associations between living alone and mortality or readmission. CONCLUSIONS: Patients living alone had delayed hospital arrival, less thrombolytic therapy, and were less likely to return home. Greater understanding of the inter-relationships among living alone, social isolation, access to stroke care, and outcomes is needed. PMID- 25139878 TI - Social network, social support, and risk of incident stroke: Atherosclerosis Risk in Communities study. AB - BACKGROUND AND PURPOSE: Having a small social network and lack of social support have been associated with incident coronary heart disease; however, epidemiological evidence for incident stroke is limited. We assessed the longitudinal association of a small social network and lack of social support with risk of incident stroke and evaluated whether the association was partly mediated by vital exhaustion and inflammation. METHODS: The Atherosclerosis Risk in Communities study measured social network and social support in 13 686 men and women (mean, 57 years; 56% women; 24% black; 76% white) without a history of stroke. Social network was assessed by the 10-item Lubben Social Network Scale and social support by a 16-item Interpersonal Support Evaluation List-Short Form. RESULTS: During a median follow-up of 18.6 years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke (hazard ratio [95% confidence interval], 1.44 [1.02-2.04]) after adjustment for demographics, socioeconomic variables, marital status, behavioral risk factors, and major stroke risk factors. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and incident stroke. Social support was unrelated to incident stroke. CONCLUSIONS: In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network may be associated with a modestly increased risk of incident stroke. PMID- 25139880 TI - A randomized trial of unruptured brain arteriovenous malformations trial: an editorial review. PMID- 25139879 TI - Sickle cell trait and incident ischemic stroke in the Atherosclerosis Risk in Communities study. AB - BACKGROUND AND PURPOSE: Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. METHODS: A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. RESULTS: SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0-2.0) and an incidence rate difference amounting to 1.9 (0.4-3.8) extra strokes per 1000 person-years. CONCLUSIONS: We observed an increased risk of ischemic stroke in blacks with SCT. Further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted. PMID- 25139881 TI - Social network and stroke risk: size matters. PMID- 25139882 TI - Quantification of the glycemic response to microdoses of subcutaneous glucagon at varying insulin levels. AB - OBJECTIVE: Glucagon delivery in closed-loop control of type 1 diabetes is effective in minimizing hypoglycemia. However, high insulin concentration lowers the hyperglycemic effect of glucagon, and small doses of glucagon in this setting are ineffective. There are no studies clearly defining the relationship between insulin levels, subcutaneous glucagon, and blood glucose. RESEARCH DESIGN AND METHODS: Using a euglycemic clamp technique in 11 subjects with type 1 diabetes, we examined endogenous glucose production (EGP) of glucagon (25, 75, 125, and 175 MUg) at three insulin infusion rates (0.016, 0.032, and 0.05 units/kg/h) in a randomized, crossover study. Infused 6,6-dideuterated glucose was measured every 10 min, and EGP was determined using a validated glucoregulatory model. Area under the curve (AUC) for glucose production was the primary outcome, estimated over 60 min. RESULTS: At low insulin levels, EGP rose proportionately with glucagon dose, from 5 +/- 68 to 112 +/- 152 mg/kg (P = 0.038 linear trend), whereas at high levels, there was no increase in glucose output (19 +/- 53 to 26 +/- 38 mg/kg, P = NS). Peak glucagon serum levels and AUC correlated well with dose (r2 = 0.63, P < 0.001), as did insulin levels with insulin infusion rates (r2 = 0.59, P < 0.001). CONCLUSIONS: EGP increases steeply with glucagon doses between 25 and 175 MUg at lower insulin infusion rates. However, high insulin infusion rates prevent these doses of glucagon from significantly increasing glucose output and may reduce glucagon effectiveness in preventing hypoglycemia when used in the artificial pancreas. PMID- 25139883 TI - Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity. AB - OBJECTIVE: In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors. RESEARCH DESIGN AND METHODS: Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. RESULTS: Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). CONCLUSIONS: This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D. PMID- 25139884 TI - Increased serum calcium levels and risk of type 2 diabetes in individuals at high cardiovascular risk. AB - OBJECTIVE: Insulin resistance and secretion depend on calcium homeostasis. Cross sectional studies have associated elevated serum calcium levels with markers of impaired glucose metabolism. However, only one prospective cohort study has demonstrated an increased risk of diabetes in individuals with increased serum calcium concentrations. The aim of the current study was to prospectively investigate the association between albumin-adjusted serum calcium concentrations and type 2 diabetes in subjects at high cardiovascular risk. RESEARCH DESIGN AND METHODS: Prospective assessment of participants from two Spanish PREDIMED study centers where serum calcium levels were measured at baseline and yearly during follow-up. Multivariate-adjusted Cox regression models were fitted to assess associations between baseline and changes during follow-up in serum calcium levels and relative risk of diabetes incidence. RESULTS: After a median follow-up of 4.78 years, 77 new cases of type 2 diabetes occurred. An increase in serum calcium levels during follow-up was related to an increased risk of diabetes. In comparison with individuals in the lowest tertile (-0.78 +/- 0.29 mg/dL), the hazard ratio (HR) and 95% CI for diabetes incidence in individuals in the higher tertile of change (0.52 +/- 0.13 mg/dL) during follow-up was 3.48 (95% CI 1.48 8.17; P for trend = 0.01). When albumin-adjusted serum calcium was analyzed as a continuous variable, per 1 mg/dL increase, the HR of diabetes incidence was 2.87 (95% CI 1.18-6.96; P value = 0.02). These associations remained significant after individuals taking calcium supplements or having calcium levels out of normal range had been excluded. CONCLUSIONS: An increase in serum calcium concentrations is associated with an increased risk of type 2 diabetes in individuals at high cardiovascular risk. PMID- 25139885 TI - Adjusting glucose-stimulated insulin secretion for adipose insulin resistance: an index of beta-cell function in obese adults. AB - OBJECTIVE: The hyperbolic relationship between insulin secretion and sensitivity has been used to assess in vivo beta-cell function (i.e., the disposition index). The disposition index emphasizes the importance of taking into account both skeletal muscle and hepatic insulin resistance to depict insulin secretion. However, we propose that adipose tissue insulin resistance also needs to be accounted for when characterizing glucose-stimulated insulin secretion (GSIS) because elevated plasma free fatty acids (FFAs) impair beta-cell function. RESEARCH DESIGN AND METHODS: To characterize the adipose disposition index, we used [1-(14)C] palmitate infusion to determine basal FFA turnover rate/adipose insulin resistance and an oral glucose tolerance test to characterize the first (i.e., 0-30 min) and second phase (i.e., 60-120 min) of GSIS. We validated a simplified version of the tracer infusion calculation as the product of (1/plasma FFA concentration * plasma insulin concentration) * GSIS in 44 obese insulin resistant subjects. RESULTS: The plasma FFA and palmitate tracer infusion calculations of the first- and second-phase disposition index were strongly correlated (r = 0.86, P < 0.000001 and r = 0.89, P < 0.000001, respectively). The first- and second-phase adipose disposition index derived from plasma FFA also was tightly associated with fasting hyperglycemia (r = -0.87, P < 0.00001 and r = -0.89, P < 0.00001, respectively) and 2-h glucose concentrations (r = -0.86, P < 0.00001 and r = -0.90, P < 0.00001). CONCLUSIONS: Adjusting GSIS for adipose insulin resistance provides an index of beta-cell function in obese subjects across the glucose spectrum. Plasma FFA-derived calculations of beta-cell function may provide additional insight into the role of adipose tissue in glucose regulation. PMID- 25139886 TI - Diabetes risk among overweight and obese metabolically healthy young adults. AB - OBJECTIVE: To determine diabetes incidence over time among obese young adults without metabolic risk factors. RESEARCH DESIGN AND METHODS: Incident diabetes during a median follow-up of 6.1 years was assessed among 33,939 young men (mean age 30.9 +/- 5.2 years) of the Metabolic, Lifestyle and Nutrition Assessment in Young Adults cohort who were stratified for BMI and the number of metabolic abnormalities (based on the Adult Treatment Panel-III). Metabolically healthy (MH) obesity was defined as BMI >=30 kg/m2 in the presence of normoglycemia, normal blood pressure, and normal levels of fasting triglyceride and HDL cholesterol levels (n = 631). RESULTS: A total of 734 new cases of diabetes were diagnosed during 210,282 person-years of follow-up. The incidence rate of diabetes among participants with no metabolic risk factors was 1.15, 2.10, and 4.34 cases per 1,000 person-years among lean, overweight, and obese participants, respectively. In a multivariable model adjusted for age, region of origin, family history of diabetes, physical activity, fasting plasma glucose, triglyceride level, HDL-cholesterol, systolic blood pressure, and white blood cell count, a higher diabetes risk was observed among MH-overweight (hazard ratio [HR] 1.89 [95% CI 1.25-2.86]; P < 0.001) and MH-obese (HR 3.88 [95% CI 1.94-7.77]; P < 0.001) compared with MH-normal weight subjects. There was no interaction between BMI and the number of metabolic abnormalities at enrollment in predicting diabetes risk. CONCLUSIONS: Healthy metabolic profile and the absence of diabetes risk factors do not protect young adults from incident diabetes associated with overweight and obesity. PMID- 25139887 TI - Serco plans to pull out of clinical service provision in the UK. PMID- 25139888 TI - Reconciling hierarchical taxonomy with molecular phylogenies. PMID- 25139889 TI - Predictive values of GPs' suspicion of serious disease are high enough to warrant subsequent investigation. PMID- 25139890 TI - Human papillomavirus (HPV) is not an equitable virus. PMID- 25139891 TI - Genitourinary medicine clinics may not see young men who have sex with men before they become infected with human papillomavirus (HPV). PMID- 25139892 TI - Effects of lifetime stress exposure on mental and physical health in young adulthood: How stress degrades and forgiveness protects health. AB - To examine risk and resilience factors that affect health, lifetime stress exposure histories, dispositional forgiveness levels, and mental and physical health were assessed in 148 young adults. Greater lifetime stress severity and lower levels of forgiveness each uniquely predicted worse mental and physical health. Analyses also revealed a graded Stress * Forgiveness interaction effect, wherein associations between stress and mental health were weaker for persons exhibiting more forgiveness. These data are the first to elucidate the interactive effects of cumulative stress severity and forgiveness on health, and suggest that developing a more forgiving coping style may help minimize stress related disorders. PMID- 25139893 TI - Attention deficit hyperactivity disorder symptomatology and pediatric obesity: Psychopathology or sleep deprivation? AB - The relationship between attention deficit hyperactivity disorder (ADHD) and obesity in children has received considerable attention in recent years. However, the literature currently overlooks the potential causal and maintaining role that sleep problems may play in this relationship. Using a biopsychosocial framework, this article highlights how sleep problems impact the biological, psychological, and social aspects of both ADHD symptomatology and obesity. An in-depth examination of this model illustrates the imperative need for future research and clinical practice to recognize and explore the role sleep has in the link between obesity and ADHD symptomatology. PMID- 25139894 TI - Relationship between infertility-related stress and emotional distress and marital satisfaction. AB - The aim of this study was to evaluate the predictive effects of infertility related stress on psychological distress and marital satisfaction. Structural equation modeling was used to estimate a nonrecursive model hypothesizing the impact of infertility-related stress on both emotional distress and marital dissatisfaction, which were supposed to have a reciprocal influence on each other. The model was estimated using data from a sample of 150 infertile patients (78 males and 72 females). Findings confirmed the predictive effects of infertility-related stress on both emotional and marital distress. However, infertility-related stress was found to have more impact on emotional distress than on marital satisfaction. PMID- 25139895 TI - Psychological resilience moderates the impact of social support on loneliness of "left-behind" children. AB - This study examined the moderator effect of psychological resilience on the relationship between social support and loneliness of the "left-behind" children. A total of 200 left-behind girls and 214 left-behind boys completed the measures of psychological resilience, social support, and loneliness. Hierarchical regression analysis showed that psychological resilience moderated the association between social support and loneliness. When left-behind children reported a low level of psychological resilience, those with high social support reported lower scores in loneliness than those with low social support. However, the impact of social support on loneliness was much smaller in the high psychological resilience group, compared with that in low psychological resilience group. PMID- 25139896 TI - Cardiovascular disease in Europe 2014: epidemiological update. AB - This paper provides an update for 2014 on the burden of cardiovascular disease (CVD), and in particular coronary heart disease (CHD) and stroke, across the countries of Europe. Cardiovascular disease causes more deaths among Europeans than any other condition, and in many countries still causes more than twice as many deaths as cancer. There is clear evidence in most countries with available data that mortality and case-fatality rates from CHD and stroke have decreased substantially over the last 5-10 years but at differing rates. The differing recent trends have therefore led to increasing inequalities in the burden of CVD between countries. For some Eastern European countries, including Russia and Ukraine, the mortality rate for CHD for 55-60 year olds is greater than the equivalent rate in France for people 20 years older. PMID- 25139897 TI - Reanalysis or redefinition of the hypothesis? PMID- 25139898 TI - A rare coronary anomaly: origin of the right coronary artery from the left ventricular outflow tract. PMID- 25139899 TI - Biofilms formed by gram-negative bacteria undergo increased lipid a palmitoylation, enhancing in vivo survival. AB - Bacterial biofilm communities are associated with profound physiological changes that lead to novel properties compared to the properties of individual (planktonic) bacteria. The study of biofilm-associated phenotypes is an essential step toward control of deleterious effects of pathogenic biofilms. Here we investigated lipopolysaccharide (LPS) structural modifications in Escherichia coli biofilm bacteria, and we showed that all tested commensal and pathogenic E. coli biofilm bacteria display LPS modifications corresponding to an increased level of incorporation of palmitate acyl chain (palmitoylation) into lipid A compared to planktonic bacteria. Genetic analysis showed that lipid A palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by the histone-like protein repressor H-NS and the SlyA regulator. While lipid A palmitoylation does not influence bacterial adhesion, it weakens inflammatory response and enhances resistance to some antimicrobial peptides. Moreover, we showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria in a clinically relevant model of catheter infection, potentially contributing to biofilm tolerance to host immune defenses. The widespread occurrence of increased lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it constitutes a new biofilm-associated phenotype in Gram-negative bacteria. IMPORTANCE: Bacterial communities called biofilms display characteristic properties compared to isolated (planktonic) bacteria, suggesting that some molecules could be more particularly produced under biofilm conditions. We investigated biofilm-associated modifications occurring in the lipopolysaccharide (LPS), a major component of all Gram-negative bacterial outer membrane. We showed that all tested commensal and pathogenic biofilm bacteria display high incorporation of a palmitate acyl chain into the lipid A part of LPS. This lipid A palmitoylation is mediated by the PagP enzyme, whose expression in biofilm is controlled by the regulatory proteins H-NS and SlyA. We also showed that lipid A palmitoylation in biofilm bacteria reduces host inflammatory response and enhances their survival in an animal model of biofilm infections. While these results provide new insights into the biofilm lifestyle, they also suggest that the level of lipid A palmitoylation could be used as an indicator to monitor the development of biofilm infections on medical surfaces. PMID- 25139900 TI - Mycobacterium tuberculosis alters the metalloprotease activity of the COP9 signalosome. AB - Inhibition of apoptotic death of macrophages by Mycobacterium tuberculosis represents an important mechanism of virulence that results in pathogen survival both in vitro and in vivo. To identify M. tuberculosis virulence determinants involved in the modulation of apoptosis, we previously screened a transposon bank of mutants in human macrophages, and an M. tuberculosis clone with a nonfunctional Rv3354 gene was identified as incompetent to suppress apoptosis. Here, we show that the Rv3354 gene encodes a protein kinase that is secreted within mononuclear phagocytic cells and is required for M. tuberculosis virulence. The Rv3354 effector targets the metalloprotease (JAMM) domain within subunit 5 of the COP9 signalosome (CSN5), resulting in suppression of apoptosis and in the destabilization of CSN function and regulatory cullin-RING ubiquitin E3 enzymatic activity. Our observation suggests that alteration of the metalloprotease activity of CSN by Rv3354 possibly prevents the ubiquitin dependent proteolysis of M. tuberculosis-secreted proteins. IMPORTANCE : Macrophage protein degradation is regulated by a protein complex called a signalosome. One of the signalosomes associated with activation of ubiquitin and protein labeling for degradation was found to interact with a secreted protein from M. tuberculosis, which binds to the complex and inactivates it. The interference with the ability to inactivate bacterial proteins secreted in the phagocyte cytosol may have crucial importance for bacterial survival within the phagocyte. PMID- 25139901 TI - Acquisition and evolution of SXT-R391 integrative conjugative elements in the seventh-pandemic Vibrio cholerae lineage. AB - SXT-R391 Integrative conjugative elements (ICEs) are self-transmissible mobile genetic elements able to confer multidrug resistance and other adaptive features to bacterial hosts, including Vibrio cholerae, the causative agent of cholera. ICEs are arranged in a mosaic genetic structure composed of a conserved backbone interspersed with variable DNA clusters located in conserved hot spots. In this study, we investigated ICE acquisition and subsequent microevolution in pandemic V. cholerae. Ninety-six ICEs were retrieved from publicly available sequence databases from V. cholerae clinical strains and were compared to a set of reference ICEs. Comparative genomics highlighted the existence of five main ICE groups with a distinct genetic makeup, exemplified by ICEVchInd5, ICEVchMoz10, SXT, ICEVchInd6, and ICEVchBan11. ICEVchInd5 (the most frequent element, represented by 70 of 96 elements analyzed) displayed no sequence rearrangements and was characterized by 46 single nucleotide polymorphisms (SNPs). SNP analysis revealed that recent inter-ICE homologous recombination between ICEVchInd5 and other ICEs circulating in gammaproteobacteria generated ICEVchMoz10, ICEVchInd6, and ICEVchBan11. Bayesian phylogenetic analyses indicated that ICEVchInd5 and SXT were independently acquired by the current pandemic V. cholerae O1 and O139 lineages, respectively, within a period of only a few years. IMPORTANCE: SXT-R391 ICEs have been recognized as key vectors of antibiotic resistance in the seventh pandemic lineage of V. cholerae, which remains a major cause of mortality and morbidity on a global scale. ICEs were acquired only recently in this clade and are acknowledged to be major contributors to horizontal gene transfer and the acquisition of new traits in bacterial species. We have reconstructed the temporal dynamics of SXT-R391 ICE acquisition and spread and have identified subsequent recombination events generating significant diversity in ICEs currently circulating among V. cholerae clinical strains. Our results showed that acquisition of SXT-R391 ICEs provided the V. cholerae seventh-pandemic lineage not only with a multidrug resistance phenotype but also with a powerful molecular tool for rapidly accessing the pan-genome of a large number of gammaproteobacteria. PMID- 25139902 TI - Genome-wide mutant fitness profiling identifies nutritional requirements for optimal growth of Yersinia pestis in deep tissue. AB - Rapid growth in deep tissue is essential to the high virulence of Yersinia pestis, causative agent of plague. To better understand the mechanisms underlying this unusual ability, we used transposon mutagenesis and high-throughput sequencing (Tn-seq) to systematically probe the Y. pestis genome for elements contributing to fitness during infection. More than a million independent insertion mutants representing nearly 200,000 unique genotypes were generated in fully virulent Y. pestis. Each mutant in the library was assayed for its ability to proliferate in vitro on rich medium and in mice following intravenous injection. Virtually all genes previously established to contribute to virulence following intravenous infection showed significant fitness defects, with the exception of genes for yersiniabactin biosynthesis, which were masked by strong intercellular complementation effects. We also identified more than 30 genes with roles in nutrient acquisition and metabolism as experiencing strong selection during infection. Many of these genes had not previously been implicated in Y. pestis virulence. We further examined the fitness defects of strains carrying mutations in two such genes-encoding a branched-chain amino acid importer (brnQ) and a glucose importer (ptsG)-both in vivo and in a novel defined synthetic growth medium with nutrient concentrations matching those in serum. Our findings suggest that diverse nutrient limitations in deep tissue play a more important role in controlling bacterial infection than has heretofore been appreciated. Because much is known about Y. pestis pathogenesis, this study also serves as a test case that assesses the ability of Tn-seq to detect virulence genes. IMPORTANCE: Our understanding of the functions required by bacteria to grow in deep tissues is limited, in part because most growth studies of pathogenic bacteria are conducted on laboratory media that do not reflect conditions prevailing in infected animal tissues. Improving our knowledge of this aspect of bacterial biology is important as a potential pathway to the development of novel therapeutics. Yersinia pestis, the plague bacterium, is highly virulent due to its rapid dissemination and growth in deep tissues, making it a good model for discovering bacterial adaptations that promote rapid growth during infection. Using Tn-seq, a genome-wide fitness profiling technique, we identified several functions required for fitness of Y. pestis in vivo that were not previously known to be important. Most of these functions are needed to acquire or synthesize nutrients. Interference with these critical nutrient acquisition pathways may be an effective strategy for designing novel antibiotics and vaccines. PMID- 25139903 TI - DNA transport across the outer and inner membranes of naturally transformable Vibrio cholerae is spatially but not temporally coupled. AB - The physiological state of natural competence for transformation allows certain bacteria to take up free DNA from the environment and to recombine such newly acquired DNA into their chromosomes. However, even though conserved components that are required to undergo natural transformation have been identified in several naturally competent bacteria, our knowledge of the underlying mechanisms of the DNA uptake process remains very limited. To better understand these mechanisms, we investigated the competence-mediated DNA transport in the naturally transformable pathogen Vibrio cholerae. Previously, we used a cell biology-based approach to experimentally address an existing hypothesis, which suggested the competence protein ComEA plays a role in the DNA uptake process across the outer membrane of Gram-negative bacteria. Here, we extended this knowledge by investigating the dynamics of DNA translocation across both membranes. More precisely, we indirectly visualized the transfer of the external DNA from outside the cell into the periplasm followed by the shuttling of the DNA into the cytoplasm. Based on these data, we conclude that for V. cholerae, the DNA translocation across the outer and inner membranes is spatially but not temporally coupled. IMPORTANCE: As a mode of horizontal gene transfer, natural competence for transformation has contributed substantially to the plasticity of genomes and to bacterial evolution. Natural competence is often a tightly regulated process and is induced by diverse environmental cues. This is in contrast to the mechanistic aspects of the DNA translocation event, which are most likely conserved among naturally transformable bacteria. However, the DNA uptake process is still not well understood. We therefore investigated how external DNA reaches the cytosol of the naturally transformable bacterium V. cholerae. More specifically, we provide evidence that the DNA translocation across the membranes is spatially but not temporally coupled. We hypothesize that this model also applies to other competent Gram-negative bacteria and that our study contributes to the general understanding of this important biological process. PMID- 25139904 TI - Annexin A2 mediates Mycoplasma pneumoniae community-acquired respiratory distress syndrome toxin binding to eukaryotic cells. AB - Mycoplasma pneumoniae synthesizes a novel human surfactant protein A (SP-A) binding cytotoxin, designated community-acquired respiratory distress syndrome (CARDS) toxin, that exhibits ADP-ribosylating and vacuolating activities in mammalian cells and is directly linked to a range of acute and chronic airway diseases, including asthma. In our attempt to detect additional CARDS toxin binding proteins, we subjected the membrane fraction of human A549 airway cells to affinity chromatography using recombinant CARDS toxin as bait. A 36-kDa A549 cell membrane protein bound to CARDS toxin and was identified by time of flight (TOF) mass spectroscopy as annexin A2 (AnxA2) and verified by immunoblotting with anti-AnxA2 monoclonal antibody. Dose-dependent binding of CARDS toxin to recombinant AnxA2 reinforced the specificity of the interaction, and further studies revealed that the carboxy terminus of CARDS toxin mediated binding to AnxA2. In addition, pretreatment of viable A549 cells with anti-AnxA2 monoclonal antibody or AnxA2 small interfering RNA (siRNA) reduced toxin binding and internalization. Immunofluorescence analysis of CARDS toxin-treated A549 cells demonstrated the colocalization of CARDS toxin with cell surface-associated AnxA2 upon initial binding and with intracellular AnxA2 following toxin internalization. HepG2 cells, which express low levels of AnxA2, were transfected with a plasmid expressing AnxA2 protein, resulting in enhanced binding of CARDS toxin and increased vacuolization. In addition, NCI-H441 cells, which express both AnxA2 and SP-A, upon AnxA2 siRNA transfection, showed decreased binding and subsequent vacuolization. These results indicate that CARDS toxin recognizes AnxA2 as a functional receptor, leading to CARDS toxin-induced changes in mammalian cells. IMPORTANCE: Host cell susceptibility to bacterial toxins is usually determined by the presence and abundance of appropriate receptors, which provides a molecular basis for toxin target cell specificities. To perform its ADP-ribosylating and vacuolating activities, community-acquired respiratory distress syndrome (CARDS) toxin must bind to host cell surfaces via receptor mediated events in order to be internalized and trafficked effectively. Earlier, we reported the binding of CARDS toxin to surfactant protein A (SP-A), and here we show how CARDS toxin uses an alternative receptor to execute its pathogenic properties. CARDS toxin binds selectively to annexin A2 (AnxA2), which exists both on the cell surface and intracellularly. Since AnxA2 regulates membrane dynamics at early stages of endocytosis and trafficking, it serves as a distinct receptor for CARDS toxin binding and internalization and enhances CARDS toxin induced vacuolization in mammalian cells. PMID- 25139905 TI - Remodeling of the intestinal brush border underlies adhesion and virulence of an enteric pathogen. AB - Intestinal colonization by Vibrio parahaemolyticus-the most common cause of seafood-borne bacterial enteritis worldwide-induces extensive disruption of intestinal microvilli. In orogastrically infected infant rabbits, reorganization of the apical brush border membrane includes effacement of some microvilli and marked elongation of others. All diarrhea, inflammation, and intestinal pathology associated with V. parahaemolyticus infection are dependent upon one of its type 3 secretion systems (T3SS2); however, translocated effectors that directly mediate brush border restructuring and bacterial adhesion are not known. Here, we demonstrate that the effector VopV is essential for V. parahaemolyticus intestinal colonization and therefore its pathogenicity, that it induces effacement of brush border microvilli, and that this effacement is required for adhesion of V. parahaemolyticus to enterocytes. VopV contains multiple functionally independent and mechanistically distinct domains through which it disrupts microvilli. We show that interaction between VopV and filamin, as well as VopV's previously noted interaction with actin, mediates enterocyte cytoskeletal reorganization. VopV's multipronged approach to epithelial restructuring, coupled with its impact on colonization, suggests that remodeling of the epithelial brush border is a critical step in pathogenesis. IMPORTANCE: Colonization of the small bowel by Vibrio parahaemolyticus, the most common bacterial agent of seafood-borne enteric disease, induces extensive structural changes in the intestinal epithelium. Here, we show that this diarrheal pathogen's colonization and virulence depend upon VopV, a bacterial protein that is transferred into host epithelial cells. VopV induces marked rearrangement of the apical epithelial cell membrane, including elimination of microvilli, by two means: through interaction with actin and through a previously unrecognized interaction with the actin-cross-linking protein filamin. VopV-mediated "effacement" of microvilli enables V. parahaemolyticus to adhere to host cells, although VopV may not directly mediate adhesion. VopV's effects on microvillus structure and bacterial adhesion likely account for its essential role in V. parahaemolyticus intestinal pathogenesis. Our findings suggest a new role for filamin in brush border maintenance and raise the possibility that microvillus effacement is a common strategy among enteric pathogens for enhancing adhesion to host cells. PMID- 25139907 TI - Young patients with hypertrophic cardiomyopathy, but not subjects at risk, show decreased myocardial perfusion reserve quantified with CMR. AB - AIMS: To determine if myocardial perfusion (MP) during hyperaemia is decreased in young patients with hypertrophic cardiomyopathy (HCM). Also, to determine if an MP decrease is associated with diastolic dysfunction, and to investigate if young subjects at risk of HCM show differences in MP compared with controls. METHODS AND RESULTS: This study included 10 HCM patients (age 22.3 +/- 6.4 years), 14 subjects at risk for HCM 'HCM risk' (age 18.9 +/- 3.8 years), and 12 controls (age 22.8 +/- 4.5 years). HCM patients were examined at rest and during hyperaemia (adenosine 140 ug/kg/min) with cardiovascular magnetic resonance (CMR) and echocardiography. MP was calculated as the ratio of coronary sinus flow and left ventricular mass (LVM) from CMR. Myocardial fibrosis was assessed using late gadolinium enhancement. Diastolic function was quantified with both echocardiography and CMR. At rest, MP (mL/min/g) was similar in the control, HCM risk, and HCM patients (0.8 +/- 0.1, 1.0 +/- 0.1, and 0.9 +/- 0.1, respectively, P = ns). During adenosine, MP was lower in HCM patients (2.5 +/- 0.4, P < 0.05) compared with both HCM risk (5.0 +/- 0.5) and controls (3.9 +/- 0.3). Subjects at HCM risk showed no significant difference in MP during adenosine compared with controls. One HCM patient showed mild diastolic dysfunction. Neither controls nor HCM risk individuals showed any sign of myocardial fibrosis, whereas 7/10 HCM patients had fibrosis (5 +/- 1% of the total LVM). CONCLUSION: Young individuals with HCM, but not those at risk, show decreased MP during hyperaemia compared with controls even in the absence of diastolic dysfunction or LV outflow obstruction. These results may suggest that microvascular disease contributes to the decreased MP in the investigated population. PMID- 25139906 TI - Echocardiographic findings in simple and complex patent foramen ovale before and after transcatheter closure. AB - AIMS: Percutaneous closure of patent foramen ovale (PFO) in cryptogenic cerebrovascular events is an alternative to medical therapy. The interpretation of residual shunts after implantation of different devices for PFO with different morphologies is controversial. METHODS AND RESULTS: Transcatheter PFO closure was performed in 123 patients with a history of >=1 paradoxical embolism using three different devices: Amplatzer (n = 46), Figulla Occlutech (n = 41), and Atriasept Cardia (n = 36). Fifty-six patients presented with simple PFO and 67 patients had complex morphologies. All patients were studied with contrast enhanced transesophageal echocardiography (TEE) before interventional procedure and thereafter at 1 and 6 months and every 6-12 months in case of incomplete closure. Definite closure was confirmed in at least two consecutive TEE studies. Various PFO morphologies were identified by TEE before device implantation. The device size to PFO diameter ratio was significantly increased in patients with complex PFO compared with those patients with a simple PFO morphology (P < 0.05). The difference between the closure rate of S-PFO and C-PFO concerning each device type was significant (Amplatzer P = 0.0027, Figulla P = 0.0043, and Atriasept P < 0.01). The mean follow-up period was 3.4 years (median 2.7 years) with a cerebrovascular re-event rate of 2.4% per year. In three patients, thrombi were detected in the 6-month TEE controls and resolved after medical therapy. In three other patients, the implantation of an adjunctive device was necessary for residual shunt. CONCLUSION: In our series of patients, the closure rate was dependent on PFO morphology more than occluder size and type. An adjunctive device was implanted in selected cases. PMID- 25139908 TI - Three-dimensional transoesophageal echocardiographic visualization of malignant anomalous left main coronary origin and course causing sudden cardiac death. PMID- 25139909 TI - Selection of chromosomal DNA libraries using a multiplex CRISPR system. AB - The directed evolution of biomolecules to improve or change their activity is central to many engineering and synthetic biology efforts. However, selecting improved variants from gene libraries in living cells requires plasmid expression systems that suffer from variable copy number effects, or the use of complex marker-dependent chromosomal integration strategies. We developed quantitative gene assembly and DNA library insertion into the Saccharomyces cerevisiae genome by optimizing an efficient single-step and marker-free genome editing system using CRISPR-Cas9. With this Multiplex CRISPR (CRISPRm) system, we selected an improved cellobiose utilization pathway in diploid yeast in a single round of mutagenesis and selection, which increased cellobiose fermentation rates by over 10-fold. Mutations recovered in the best cellodextrin transporters reveal synergy between substrate binding and transporter dynamics, and demonstrate the power of CRISPRm to accelerate selection experiments and discoveries of the molecular determinants that enhance biomolecule function. PMID- 25139910 TI - Determining protein complex structures based on a Bayesian model of in vivo Forster resonance energy transfer (FRET) data. AB - The use of in vivo Forster resonance energy transfer (FRET) data to determine the molecular architecture of a protein complex in living cells is challenging due to data sparseness, sample heterogeneity, signal contributions from multiple donors and acceptors, unequal fluorophore brightness, photobleaching, flexibility of the linker connecting the fluorophore to the tagged protein, and spectral cross-talk. We addressed these challenges by using a Bayesian approach that produces the posterior probability of a model, given the input data. The posterior probability is defined as a function of the dependence of our FRET metric FRETR on a structure (forward model), a model of noise in the data, as well as prior information about the structure, relative populations of distinct states in the sample, forward model parameters, and data noise. The forward model was validated against kinetic Monte Carlo simulations and in vivo experimental data collected on nine systems of known structure. In addition, our Bayesian approach was validated by a benchmark of 16 protein complexes of known structure. Given the structures of each subunit of the complexes, models were computed from synthetic FRETR data with a distance root-mean-squared deviation error of 14 to 17 A. The approach is implemented in the open-source Integrative Modeling Platform, allowing us to determine macromolecular structures through a combination of in vivo FRETR data and data from other sources, such as electron microscopy and chemical cross-linking. PMID- 25139912 TI - External manifestations of Gardner's syndrome as the presenting clinical entity. AB - Gardner's syndrome is an autosomal dominant disease characterised by the presence of colonic polyposis, osteomas and a multitude of soft tissue tumours. Pathological features such as osteomas of the mandible, skull and facial skeleton are unaesthetic as well as incapacitating. We present the case of a 22-year-old man with pain and discharge from the left eye and a firm swelling in the left infraorbital region leading to proptosis of the left eye. A detailed examination of the patient led to the presence of a large osteoma in the left orbital region, multiple cystic lesion, corneal opacity and parapapillary atrophy in the left eye. Radiography revealed the presence of multiple unerupted supernumerary teeth and osteomas. Colonoscopic findings showed the presence of multiple polyps. Thus, external manifestations of the patient's facial region led to the establishment of the diagnosis of Gardner's syndrome. The importance of our case highlights the necessity of maintaining a high vigilance with regard to the occurrence of such an entity. PMID- 25139913 TI - Periorbital purpura (raccoon's eyes). PMID- 25139914 TI - Gingival squamous cell carcinoma presenting as periodontal lesion in the mandibular posterior region. AB - Gingival squamous cell carcinoma (GSCC) is a relatively rare malignant neoplasm of the oral cavity. It represents less than 10% of diagnosed intraoral carcinoma. Because of its close proximity to the teeth and periodontium, the tumour can mimic tooth-related benign inflammatory conditions. This case report describes a patient diagnosed with GSCC presenting as localised periodontitis. PMID- 25139911 TI - Integrative structure-function mapping of the nucleoporin Nup133 suggests a conserved mechanism for membrane anchoring of the nuclear pore complex. AB - The nuclear pore complex (NPC) is the sole passageway for the transport of macromolecules across the nuclear envelope. Nup133, a major component in the essential Y-shaped Nup84 complex, is a large scaffold protein of the NPC's outer ring structure. Here, we describe an integrative modeling approach that produces atomic models for multiple states of Saccharomyces cerevisiae (Sc) Nup133, based on the crystal structures of the sequence segments and their homologs, including the related Vanderwaltozyma polyspora (Vp) Nup133 residues 55 to 502 (VpNup133(55 502)) determined in this study, small angle X-ray scattering profiles for 18 constructs of ScNup133 and one construct of VpNup133, and 23 negative-stain electron microscopy class averages of ScNup133(2-1157). Using our integrative approach, we then computed a multi-state structural model of the full-length ScNup133 and validated it with mutational studies and 45 chemical cross-links determined via mass spectrometry. Finally, the model of ScNup133 allowed us to annotate a potential ArfGAP1 lipid packing sensor (ALPS) motif in Sc and VpNup133 and discuss its potential significance in the context of the whole NPC; we suggest that ALPS motifs are scattered throughout the NPC's scaffold in all eukaryotes and play a major role in the assembly and membrane anchoring of the NPC in the nuclear envelope. Our results are consistent with a common evolutionary origin of Nup133 with membrane coating complexes (the protocoatomer hypothesis); the presence of the ALPS motifs in coatomer-like nucleoporins suggests an ancestral mechanism for membrane recognition present in early membrane coating complexes. PMID- 25139915 TI - Psychosis with Huntington's disease: role of antipsychotic medications. AB - This is a case of a 60-year-old man who presented with a 6-month history of increasing agitation and emotional volatility. His family brought him to the emergency room as they were concerned about his threatening and aggressive behaviour. The patient was initially incoherent and uncooperative. During the interview, the patient's family revealed that he had a previous diagnosis of Huntington's disease; there was also a family history of personality changes preceding Huntington's chorea. The patient was admitted to the psychiatric inpatient unit and started on low-dose risperidone. Consequently, there was marked improvement in his symptoms. Subsequent cognitive tests revealed deficits in multiple domains. After a month, the patient was discharged to a community home in stable state. PMID- 25139916 TI - Disseminated histoplasmosis in an HIV patient with CD4 count of 1 cell/uL. AB - We report a case of a young woman with advanced HIV/AIDS who presented with a short duration of fever and shortness of breath, with no recent travel history or previous hospitalisation, accompanied by non-specific abdominal symptoms and suspicious upper gastrointestinal bleed. Her CD4 count was 1 cell/MUL raising the suspicious for various opportunistic aetiologies. The initial suspicion was for pneumocystis pneumonia (PCP) and the patient was treated empirically with antimicrobials. Peripheral smear findings, urinary antigen tests and bronchoalveolar lavage (BAL) were suggestive of disseminated histoplasmosis. PCP was ruled out in BAL. Transabdominal imaging was concerning for periaortic lymphadenopathy raising the suspicion of occult malignancy. Endoscopic evaluation of her digestive tract was unrevealing. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) confirmed histoplasmosis. She received a liposomal amphotericin B for 10 days followed by itraconazole with significant improvement. Her CD4 count was found to be the lowest reported count with a single opportunistic pathogen. PMID- 25139917 TI - The disappearing clip: an unusual complication in MRI biopsy. AB - MRI-guided biopsies are being increasingly used for otherwise occult breast lesions. Clip migration has been reported however, to the best of our knowledge, there have been no documented cases of entire disappearance of a marker clip. Absence of the postbiopsy marker clip was noted when our patient returned for preoperative hook-wire localisation even though accurate clip placement had been confirmed on the post-MRI biopsy mammogram. PMID- 25139919 TI - Fatal measles presenting as acute respiratory distress syndrome in an immunocompetent adult. AB - Fatal measles is known to occur among immunocompromised adults. We report a rare case of an immunocompetent non-pregnant young lady who suffered from fatal acute respiratory distress syndrome due to measles. Physicians must be vigilant to this deadly presentation of measles even in immunocompetent individuals. We emphasise the inadequacies of vaccination programmes in India reflected not only by the existing high measles-related childhood mortalities, but also an emerging rise in deaths among adults. PMID- 25139918 TI - Parathyroid carcinoma, a rare cause of primary hyperparathyroidism. AB - A 45 year-old woman who presented with non-specific neck and shoulder pain, was found to have mild hypercalcaemia, markedly elevated parathyroid hormone levels, and an irregular parathyroid gland on imaging. The patient underwent a parathyroidectomy and the pathology report came back positive for parathyroid carcinoma with muscular invasion. Parathyroid carcinoma is an exceptionally rare cause of primary hyperparathyroidism and can have a poor prognosis due to metastases and a high propensity to recur after resection. Reports of non functioning parathyroid carcinomas tend to behave even more aggressively. Repeat imaging on this patient showed residual cancer present, so the patient underwent a second surgery with radical neck dissection and has since been doing very well postoperatively. Diagnosis and treatment is challenging and it is critical to continuously follow-up for recurrent disease. PMID- 25139920 TI - An unusual cause of haemoptysis: isolated tracheobronchial amyloidosis. PMID- 25139921 TI - Eyelid reanimation, neurotisation, and transplantation of the cornea in a patient with facial palsy. AB - Patients affected by facial palsy suffer from failure to fully close the eyelids; the resulting eye exposure can lead to dry eye syndrome, loss of epithelial integrity, corneal ulceration and infections. Corneal anaesthesia exacerbates risk of corneal damage in these patients. Eyelid paralysis-associated corneal lesions may induce severe visual impairment, for which the ideal treatment is corneal transplantation, a procedure contraindicated in patients with corneal sensitivity and inadequate eyelid closure. We present the case of a patient affected by unilateral facial palsy associated with corneal anaesthesia, due to seventh and fifth cranial nerve damage following homolateral eighth cranial nerve surgery. The patient underwent surgery to re-establish eyelid and corneal competence, and then received a corneal graft with consequent amelioration of visual acuity. This is the first case of associated corneal anaesthesia and facial palsy that was comprehensively treated with a set of surgical procedures, including a corneal transplant. PMID- 25139922 TI - Transient cefuroxime/metronidazole treatment induced factor V antibodies. AB - A 29-year-old patient presented with an appendicular infiltrate, initially treated with intravenous antibiotics, but later requiring percutaneous drainage. Both prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged on 3 days of antibiotic treatment and unresponsive to vitamin K or prothrombin complex concentrate. Laboratory investigation ultimately showed reduced factor V activity and factor V antibodies. In contrast to previously described cases of factor V antibodies, PT and aPTT were only mildly prolonged and residual factor V activity was still >20%. Draining of the abscess did not induce significant bleeding. Afterwards, no haemostatic medication was required. The patient was discharged from the hospital without complications. One week after cessation of the antibiotic treatment, PT and aPTT were within normal range again, with a factor V activity level of 36%. In conclusion, we present a patient with transient factor V antibodies, induced by antibiotics, without clinical bleeding tendency. PMID- 25139923 TI - Post-traumatic iridodialysis, crystalline dislocation and vitreous haemorrhage: how to manage. AB - A 66-year-old man, while taking care of his horse, sustained a blunt, non penetrating injury to the right side of his face, which damaged his eye. On slit lamp examination, iris dialysis and crystalline dislocation in the vitreous chamber were observed. On presentation, his best correct visual acuity was hand motion. A 23 G vitrectomy and subsequently an iris reconstruction and a glued intraocular lens implant were performed. Visual acuity reached +0.1 logMAR 1 month after surgery and remained stable after 12 months' follow-up. PMID- 25139924 TI - Haemophagocytic lymphohistiocytosis associated with coccidiomycosis. AB - Haemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by dysregulated histiocytes leading to an excessive inflammatory reaction. While genetic forms of HLH exist, the most common form is acquired, frequently associated with infection. Here we report the first case of HLH associated with a coccidiomycosis infection. This patient is a 13-year-old previously healthy boy who presented with a flu-like illness, which rapidly progressed to refractory shock, severe ARDS, multiorgan failure and death despite maximal medical therapy, including broad-spectrum antibiotics to treat well-established causes of acquired HLH. Autopsy findings revealed the diagnosis of HLH in the setting of pulmonary coccidiomycosis. Antifungal therapy should be considered in cases of acquired HLH when the underlying aetiology is not clear. PMID- 25139925 TI - Giant suprasellar arachnoid cyst presenting with precocious puberty. PMID- 25139926 TI - Obstructed ileostomy in the third trimester of pregnancy due to compression from the gravid uterus: diagnosis and management. AB - Ileostomy obstruction in pregnancy, although rare, is a significant complication with associated morbidity and mortality. Early studies recommended immediate surgical intervention for cases of ileostomy obstruction in pregnancy. We present a case of ileostomy obstruction at 29-week gestation in which a laparotomy was performed for presumed adhesions. When adhesiolysis failed to resolve the obstruction, it became clear that the obstruction was caused by external compression from the enlarging gravid uterus. The remainder of the pregnancy was successfully managed by daily aspiration of bowel contents using a large bore drainage tube, and total parental nutrition. Recent studies have utilised MRI to distinguish between adhesions and uterine compression as the cause of ileostomy obstruction in pregnancy. In the few cases of obstruction caused by uterine compression, patients have been safely managed with conservative therapy, thereby avoiding the risks of surgery. PMID- 25139927 TI - Urinoma formation following laparoscopic oophorectomy. PMID- 25139928 TI - A giant myxoma arising from the free wall of the right atria. PMID- 25139929 TI - Mislaid dentures: a cause for unusual presentation of bilateral vocal cord palsy. AB - An 81-year-old man was referred urgently to the head and neck clinic with symptoms of worsening dysphagia, dysphonia and weight loss. He had a history of chronic lymphocytic leukaemia. On full ear, nose and throat examination, he was found to have fixed vocal cords with pooling of saliva in the bilateral pyriform fossa. Hypopharyngeal malignancy was suspected and further imaging was performed. Imaging also raised the suspicion of malignancy in the hypopharynx. Rigid endoscopic examination under general anaesthesia was carried out which revealed an impacted denture in the cricopharynx and upper oesophagus. The patient was aware of his loss of dentures 3 months ago (corresponds to the onset of his symptoms) but felt that he had mislaid them and had never mentioned this to anyone. We present a case highlighting a delay in diagnosis, a missed diagnosis on CT scan and an unusual presentation leading to bilateral vocal cord paresis. PMID- 25139930 TI - Editorial. PMID- 25139931 TI - A reflection of outcomes research and its impact on the practice of hand surgery. PMID- 25139932 TI - One mum too few: maternal status in host surrogate motherhood arrangements. AB - In a host surrogate motherhood arrangement, the surrogate agrees to be implanted with, and carry to term, an embryo created from the commissioning couple's gametes. When the surrogate child is born, it is the surrogate mother who, according to UK law, holds the legal status of mother. By contrast, the commissioning mother possesses no maternal status and she can only attain it once the surrogate agrees to the completion of the arrangement. One consequence of this is that, in the event that a host arrangement fails, the commissioning mother is left without maternal status. In this paper, I argue that this denial of maternal status misrepresents the commissioning mother's role in the host arrangement and her relationship with the surrogate child. Consequently, I suggest that commissioning mothers participating in host surrogacy arrangements ought to be granted the status of mother in the event that the arrangement fails. PMID- 25139933 TI - A case of consent. PMID- 25139934 TI - Forced-Attention Dichotic Listening With University Students With Dyslexia: Search for a Core Deficit. AB - Rapidly changing environments in day-to-day activities, enriched with stimuli competing for attention, require a cognitive control mechanism to select relevant stimuli, ignore irrelevant stimuli, and shift attention between alternative features of the environment. Such attentional orchestration is essential to the acquisition of reading skills. In the present forced attention dichotic listening study, adults with moderate and severe dyslexia and nondisabled adults were tested on their ability to switch attention between ears for immediate recall. Blocks of pairs of consonant-vowel syllables were counterbalanced into left-ear first or right-ear first ordered conditions. Significant order effects showed that only those with severe dyslexia were poorer in switching attention to the left ear, whereas both groups with dyslexia were poorer switching attention to the right ear. Shifting left appears to be a normative function of reading level, whereas inferior ability to disengage attending to the left ear to report from the right ear qualifies as a dysfunctional facet of dyslexia with etiological significance. No support was found for the traditional proposition that dyslexia may be associated with atypical left hemisphere lateralization. Combining these results with previous dichotic and neuroimaging research implicates a dysfunctional frontostriatal cognitive control network in dyslexia. With due caution, the results suggest that a neurobiological feature of dyslexia may be a lack of control in downwardly modulating excessive left inferior frontal cortex activations. The results are consistent with impoverished connectedness between left anterior and posterior language areas and, pending future confirmation of these findings, suggest the need for a reconceptualization of remedial programming. PMID- 25139935 TI - Comparison of mammographic density assessed as volumes and areas among women undergoing diagnostic image-guided breast biopsy. AB - BACKGROUND: Mammographic density (MD), the area of non-fatty-appearing tissue divided by total breast area, is a strong breast cancer risk factor. Most MD analyses have used visual categorizations or computer-assisted quantification, which ignore breast thickness. We explored MD volume and area, using a volumetric approach previously validated as predictive of breast cancer risk, in relation to risk factors among women undergoing breast biopsy. METHODS: Among 413 primarily white women, ages 40 to 65 years, undergoing diagnostic breast biopsies between 2007 and 2010 at an academic facility in Vermont, MD volume (cm(3)) was quantified in craniocaudal views of the breast contralateral to the biopsy target using a density phantom, whereas MD area (cm(2)) was measured on the same digital mammograms using thresholding software. Risk factor associations with continuous MD measurements were evaluated using linear regression. RESULTS: Percent MD volume and area were correlated (r = 0.81) and strongly and inversely associated with age, body mass index (BMI), and menopause. Both measures were inversely associated with smoking and positively associated with breast biopsy history. Absolute MD measures were correlated (r = 0.46) and inversely related to age and menopause. Whereas absolute dense area was inversely associated with BMI, absolute dense volume was positively associated. CONCLUSIONS: Volume and area MD measures exhibit some overlap in risk factor associations, but divergence as well, particularly for BMI. IMPACT: Findings suggest that volume and area density measures differ in subsets of women; notably, among obese women, absolute density was higher with volumetric methods, suggesting that breast cancer risk assessments may vary for these techniques. PMID- 25139937 TI - Association of leukocyte mitochondrial DNA copy number with colorectal cancer risk: Results from the Shanghai Women's Health Study. AB - BACKGROUND: Mitochondria play an important role in cellular energy metabolism, free radical production, and apoptosis, and thus may be involved in cancer development. METHODS: We evaluated mitochondrial DNA (mtDNA) copy number in peripheral leukocytes in relation to colorectal cancer risk in a case-control study of 444 colorectal cancer cases and 1,423 controls nested in the Shanghai Women's Health Study, a population-based, prospective cohort study. Relative mtDNA copy number was determined by a quantitative real-time PCR assay using peripheral leukocyte DNA samples collected at the time of study enrollment, before cancer diagnosis. RESULTS: We found that baseline mtDNA copy number was lower among women who subsequently developed colorectal cancer [geometric mean, 0.277; 95% confidence interval (CI), 0.269-0.285] than among women who remained cancer-free (geometric mean, 0.288; 95% CI, 0.284-0.293; P = 0.0153). Multivariate adjusted ORs were 1.26 (95% CI, 0.93-1.70) and 1.44 (95% CI, 1.06 1.94) for the middle and lower tertiles of mtDNA copy number, respectively, compared with the upper tertile (highest mtDNA copy number; Ptrend = 0.0204). The association varied little by the interval between blood collection and cancer diagnosis. CONCLUSIONS: Our data suggest that mtDNA copy number measured in peripheral leukocytes may be a potential biomarker useful for colorectal cancer risk assessment. IMPACT: If confirmed, mtDNA copy number measured in peripheral leukocytes may be a biomarker useful for colorectal cancer risk assessment. PMID- 25139938 TI - What is the risk of having a total hip or knee replacement for patients with lupus? AB - Individuals with systemic lupus erythematosus (SLE) frequently have arthralgia but joint damage leading to surgery is thought to be less common. In addition to inflammatory damage, other reasons like avascular necrosis (AVN), which is often associated with steroid use, excessive alcohol intake and antiphospholipid syndrome (APS), may increase the likelihood of large joint failure. In this study we aimed to determine the likelihood of having a total hip replacement (THR) or total knee replacement (TKR) for individuals with SLE compared to those without lupus, by performing a retrospective matched case control study of all THRs and TKRs that were performed between 1991 and 2011 and recorded in the General Practice Research Database (GPRD). Individuals with inflammatory arthritis due to any other causes were excluded and the results were adjusted for steroid use, alcohol consumption (drinking status) and APS. The results show that patients with lupus who had a THR or TKR were younger than their peers without lupus. In addition, they appeared to have a significantly increased risk of TKR but the increased risk of THR did not remain after adjustment for steroid use, alcohol consumption and APS. PMID- 25139936 TI - Association of cancer susceptibility variants with risk of multiple primary cancers: The population architecture using genomics and epidemiology study. AB - BACKGROUND: Multiple primary cancers account for approximately 16% of all incident cancers in the United States. Although genome-wide association studies (GWAS) have identified many common genetic variants associated with various cancer sites, no study has examined the association of these genetic variants with risk of multiple primary cancers (MPC). METHODS: As part of the National Human Genome Research Institute (NHGRI) Population Architecture using Genomics and Epidemiology (PAGE) study, we used data from the Multiethnic Cohort (MEC) and Women's Health Initiative (WHI). Incident MPC (IMPC) cases (n = 1,385) were defined as participants diagnosed with more than one incident cancer after cohort entry. Participants diagnosed with only one incident cancer after cohort entry with follow-up equal to or longer than IMPC cases served as controls (single index cancer controls; n = 9,626). Fixed-effects meta-analyses of unconditional logistic regression analyses were used to evaluate the associations between 188 cancer risk variants and IMPC risk. To account for multiple comparisons, we used the false-positive report probability (FPRP) to determine statistical significance. RESULTS: A nicotine dependence-associated and lung cancer variant, CHRNA3 rs578776 [OR, 1.16; 95% confidence interval (CI), 1.05-1.26; P = 0.004], and two breast cancer variants, EMBP1 rs11249433 and TOX3 rs3803662 (OR, 1.16; 95% CI, 1.04-1.28; P = 0.005 and OR, 1.13; 95% CI, 1.03-1.23; P = 0.006), were significantly associated with risk of IMPC. The associations for rs578776 and rs11249433 remained (P < 0.05) after removing subjects who had lung or breast cancers, respectively (P <= 0.046). These associations did not show significant heterogeneity by smoking status (Pheterogeneity >= 0.53). CONCLUSIONS: Our study has identified rs578776 and rs11249433 as risk variants for IMPC. IMPACT: These findings may help to identify genetic regions associated with IMPC risk. PMID- 25139939 TI - A new trick for an ancient drug: quinine dissociates antiphospholipid immune complexes. AB - Quinine, a quinoline derivative, is an ancient antipyretic drug with antimalarial properties that has been phased out by more effective synthetic candidates. In previous studies we discovered that hydroxychloroquine (HCQ), a synthetic antimalarial with structural similarities to quinine, reduced the binding of antiphospholipid (aPL) immune complexes to phospholipid bilayers. We performed ellipsometry and atomic force microscopy (AFM) studies to measure the effect of quinine on dissociation of anti-beta2-glycoprotein I (anti-beta2GPI) immune complexes. We found that quinine desorbed pre-formed beta2GPI-aPL immunoglobulin (Ig)G complexes from phospholipid bilayers at significantly lower molar concentrations than HCQ. Quinine also inhibited the formation of immune complexes with a higher efficacy than HCQ at equivalent drug concentrations of 0.2 mg/ml (0.192 +/- 0.025 ug/cm(2) for quinine vs. 0.352 +/- 0.014 ug/cm(2) for HCQ, p < 0.001). Furthermore, AFM imaging experiments revealed that addition of quinine disintegrated immune complexes bound to planar phospholipid layers. The desorptive and inhibitory effects of the old drug, quinine, toward beta2GPI-aPL IgG complexes and beta2GPI were significantly more pronounced compared to the synthetic antimalarial, HCQ. The results suggest that the quinoline core of the molecule is a critical domain for this activity and that side chains may further modulate this effect. The results also indicate that there may yet be room for considering new activities of very old drugs in devising clinical trials on potential non-anticoagulant treatments for antiphospholipid syndrome (APS). PMID- 25139940 TI - Fatal tusk injuries from a wild boar attack. AB - Injuries caused by wild boar attacks are rare. The pattern of the tusk injuries by wild boar is rarely been mentioned in literature. Such injuries can be termed "tusk injuries". Herein, we discuss the pattern of a wild boar tusk wound following an attack on a 65-year-old man who sustained fatal injuries as a result. PMID- 25139943 TI - Atrophy and structural variability of the upper cervical cord in early multiple sclerosis. AB - BACKGROUND: Despite agreement about spinal cord atrophy in progressive forms of multiple sclerosis (MS), data on clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS) are conflicting. OBJECTIVE: To determine the onset of spinal cord atrophy in the disease course of MS. METHODS: Structural brain magnetic resonance imaging (MRI) was acquired from 267 patients with CIS (85) or RRMS (182) and 64 healthy controls (HCs). The upper cervical cord cross-sectional area (UCCA) was determined at the level of C2/C3 by a segmentation tool and adjusted for focal MS lesions. The coefficient of variation (CV) was calculated from all measurements between C2/C3 and 13 mm above as a measure of structural variability. RESULTS: Compared to HCs (76.1+/-6.9 mm(2)), UCCA was significantly reduced in CIS patients (73.5+/-5.8 mm(2), p=0.018) and RRMS patients (72.4+/-7.0 mm(2), p<0.001). Structural variability was higher in patients than in HCs, particularly but not exclusively in case of focal lesions (mean CV HCs/patients without/with lesions: 2.13%/2.55%/3.32%, all p-values<0.007). UCCA and CV correlated with Expanded Disability Status Scale (EDSS) scores (r =-0.131/0.192, p=0.044/<0.001) and disease duration (r=-0.134/0.300, p=0.039/< 0.001). CV additionally correlated with hand and arm function (r=0.180, p=0.014). CONCLUSION: In MS, cervical cord atrophy already occurs in CIS. In early stages, structural variability may be a more meaningful marker of spinal cord pathology than atrophy. PMID- 25139941 TI - Cortical Brain Activity Reflecting Attentional Biasing Toward Reward-Predicting Cues Covaries with Economic Decision-Making Performance. AB - Adaptive choice behavior depends critically on identifying and learning from outcome-predicting cues. We hypothesized that attention may be preferentially directed toward certain outcome-predicting cues. We studied this possibility by analyzing event-related potential (ERP) responses in humans during a probabilistic decision-making task. Participants viewed pairs of outcome predicting visual cues and then chose to wager either a small (i.e., loss minimizing) or large (i.e., gain-maximizing) amount of money. The cues were bilaterally presented, which allowed us to extract the relative neural responses to each cue by using a contralateral-versus-ipsilateral ERP contrast. We found an early lateralized ERP response, whose features matched the attention-shift related N2pc component and whose amplitude scaled with the learned reward predicting value of the cues as predicted by an attention-for-reward model. Consistently, we found a double dissociation involving the N2pc. Across participants, gain-maximization positively correlated with the N2pc amplitude to the most reliable gain-predicting cue, suggesting an attentional bias toward such cues. Conversely, loss-minimization was negatively correlated with the N2pc amplitude to the most reliable loss-predicting cue, suggesting an attentional avoidance toward such stimuli. These results indicate that learned stimulus reward associations can influence rapid attention allocation, and that differences in this process are associated with individual differences in economic decision-making performance. PMID- 25139944 TI - A rare case of hyponatremia from a hypothalamic lesion in a patient with multiple sclerosis. AB - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur from a variety of neurologic and systemic processes; however, it has rarely been seen in multiple sclerosis (MS). We report a case of SIADH in a patient with MS and compare it with previously reported English-only cases. A 32-year-old woman experienced generalized fatigue followed by confusion and was found to have profound hyponatremia. Her work-up demonstrated SIADH secondary to a discrete enhancing hypothalamic lesion. Despite the seldom occurrence of SIADH in MS, hypothalamic lesions are more common than appreciated and should be considered in patients presenting with hyponatremia or endocrinopathy symptoms. PMID- 25139945 TI - Paroxysmal dysarthria ataxia syndrome responds to lacosamide. PMID- 25139946 TI - Cortical thickness and surface area relate to specific symptoms in early relapsing-remitting multiple sclerosis. AB - BACKGROUND: Cortical atrophy is common in early relapsing-remitting multiple sclerosis (RRMS). Whether this atrophy is caused by changes in cortical thickness or cortical surface area is not known, nor is their separate contributions to clinical symptoms. OBJECTIVES: To investigate the difference in cortical surface area, thickness and volume between early RRMS patients and healthy controls; and the relationship between these measures and neurological disability, cognitive decline, fatigue and depression. METHODS: RRMS patients (n = 61) underwent magnetic resonance imaging (MRI), neurological and neuropsychological examinations. We estimated cortical surface area, thickness and volume and compared them with matched healthy controls (n = 61). We estimated the correlations between clinical symptoms and cortical measures within the patient group. RESULTS: We found no differences in cortical surface area, but widespread differences in cortical thickness and volume between the groups. Neurological disability was related to regionally smaller cortical thickness and volume. Better verbal memory was related to regionally larger surface area; and better visuo-spatial memory, to regionally larger cortical volume. Higher depression scores and fatigue were associated with regionally smaller cortical surface area and volume. CONCLUSIONS: We found that cortical thickness, but not cortical surface area, is affected in early RRMS. We identified specific structural correlates to the main clinical symptoms in early RRMS. PMID- 25139948 TI - Deletion of the Synechocystis sp. PCC 6803 kaiAB1C1 gene cluster causes impaired cell growth under light-dark conditions. AB - In contrast to Synechococcus elongatus PCC 7942, few data exist on the timing mechanism of the widely used cyanobacterium Synechocystis sp. PCC 6803. The standard kaiAB1C1 operon present in this organism was shown to encode a functional KaiC protein that interacted with KaiA, similar to the S. elongatus PCC 7942 clock. Inactivation of this operon in Synechocystis sp. PCC 6803 resulted in a mutant with a strong growth defect when grown under light-dark cycles, which was even more pronounced when glucose was added to the growth medium. In addition, mutants showed a bleaching phenotype. No effects were detected in mutant cells grown under constant light. Microarray experiments performed with cells grown for 1 day under a light-dark cycle revealed many differentially regulated genes with known functions in the DeltakaiABC mutant in comparison with the WT. We identified the genes encoding the cyanobacterial phytochrome Cph1 and the light-repressed protein LrtA as well as several hypothetical ORFs with a complete inverse behaviour in the light cycle. These transcripts showed a stronger accumulation in the light but a weaker accumulation in the dark in DeltakaiABC cells in comparison with the WT. In general, we found a considerable overlap with microarray data obtained for hik31 and sigE mutants. These genes are known to be important regulators of cell metabolism in the dark. Strikingly, deletion of the DeltakaiABC operon led to a much stronger phenotype under light-dark cycles in Synechocystis sp. PCC 6803 than in Synechococcus sp. PCC 7942. PMID- 25139950 TI - Epidemiological survey of head and neck injuries and trauma in the United States. AB - OBJECTIVE: Head and neck trauma results in a range of injuries, spanning minor lacerations to life-threatening airway compromise. Few studies provide in-depth analysis of injuries to the head and neck (HN). We aim to (1) describe HN injury prevalence in the US and (2) investigate patient disposition and the outcome of mortality. STUDY DESIGN: Case series with chart review. SETTING: Nationwide emergency department (ED) sample. METHODS: The 2011 database was queried for encounters with a primary diagnosis of HN injury, as categorized by the Barell Injury Matrix. Weighted estimates for demographics, injury category, and mechanism were extracted. Predictors of mortality and admission were determined by multivariable regression. RESULTS: We identified 131 million ED encounters. A weighted total of 5,418,539 visits were related to primary HN injuries. Average age was 30 (SE = 0.4), and 56.8% were male. Sixty-four percent of injuries were attributed to fall or blunt trauma. Open wounds comprised 41.8% of injuries. The most common procedure was laceration repair (70%). The majority of patients (97%) were discharged home. Mortality rate was less than 1%. Predictors of admission and mortality (P < .05) included multiple trauma, vessel trauma, and burns. Other risk factors included foreign-body, older age, and male gender. CONCLUSIONS: Primary HN injuries commonly present to emergency rooms in the US. The majority of HN injuries are non-life threatening and do not require admission to the hospital or result in death. These data have implications for HN injury surveillance and may be used to risk-stratify patients who present with injuries in the acute care setting. PMID- 25139949 TI - Dissection of the region of Pseudomonas aeruginosa ParA that is important for dimerization and interactions with its partner ParB. AB - Pseudomonas aeruginosa ParA belongs to a large subfamily of Walker-type ATPases acting as partitioning proteins in bacteria. ParA has the ability to both self associate and interact with its partner ParB. Analysis of the deletion mutants defined the part of the protein involved in dimerization and interactions with ParB. Here, a set of ParA alanine substitution mutants in the region between E67 and L85 was created and analysed in vivo and in vitro. All mutants impaired in dimerization (substitutions at positions M74, H79, Y82 and L84) were also defective in interactions with ParB, suggesting that ParA-ParB interactions depend on the ability of ParA to dimerize. Mutants with alanine substitutions at positions E67, C68, L70, E72, F76, Q83 and L85 were not impaired in dimerization, but were defective in interactions with ParB. The dimerization interface partly overlapped the pseudo-hairpin, involved in interactions with ParB. ParA mutant derivatives tested in vitro showed no defects in ATPase activity. Two parA alleles (parA84, whose product can neither self-interact nor interact with ParB, and parA67, whose product is impaired in interactions with ParB, but not in dimerization) were introduced into the P. aeruginosa chromosome by homologous gene exchange. Both mutants showed defective separation of ParB foci, but to different extents. Only PAO1161 parA84 was visibly impaired in terms of chromosome segregation, growth rate and motility, similar to a parA-null mutant. PMID- 25139951 TI - Tension pneumocephalus after endoscopic sinus surgery: a technical report of multiportal endoscopic skull base repair. PMID- 25139953 TI - Shared mushroom body circuits underlie visual and olfactory memories in Drosophila. AB - In nature, animals form memories associating reward or punishment with stimuli from different sensory modalities, such as smells and colors. It is unclear, however, how distinct sensory memories are processed in the brain. We established appetitive and aversive visual learning assays for Drosophila that are comparable to the widely used olfactory learning assays. These assays share critical features, such as reinforcing stimuli (sugar reward and electric shock punishment), and allow direct comparison of the cellular requirements for visual and olfactory memories. We found that the same subsets of dopamine neurons drive formation of both sensory memories. Furthermore, distinct yet partially overlapping subsets of mushroom body intrinsic neurons are required for visual and olfactory memories. Thus, our results suggest that distinct sensory memories are processed in a common brain center. Such centralization of related brain functions is an economical design that avoids the repetition of similar circuit motifs. PMID- 25139954 TI - Autism and attention-deficit/hyperactivity disorder among individuals with a family history of alcohol use disorders. AB - Recent studies suggest de novo mutations may involve the pathogenesis of autism and attention-deficit/hyperactivity disorder (ADHD). Based on the evidence that excessive alcohol consumption may be associated with an increased rate of de novo mutations in germ cells (sperms or eggs), we examine here whether the risks of autism and ADHD are increased among individuals with a family history of alcohol use disorders (AUDs). The standardized incidence ratios (SIRs) of autism and ADHD among individuals with a biological parental history of AUDs were 1.39 (95% CI 1.34-1.44) and 2.19 (95% CI 2.15-2.23), respectively, compared to individuals without an affected parent. Among offspring whose parents were diagnosed with AUDs before their birth, the corresponding risks were 1.46 (95% CI 1.36-1.58) and 2.70 (95% CI 2.59-2.81), respectively. Our study calls for extra surveillance for children with a family history of AUDs, and further studies examining the underlying mechanisms are needed. PMID- 25139955 TI - A suppression hierarchy among competing motor programs drives sequential grooming in Drosophila. AB - Motor sequences are formed through the serial execution of different movements, but how nervous systems implement this process remains largely unknown. We determined the organizational principles governing how dirty fruit flies groom their bodies with sequential movements. Using genetically targeted activation of neural subsets, we drove distinct motor programs that clean individual body parts. This enabled competition experiments revealing that the motor programs are organized into a suppression hierarchy; motor programs that occur first suppress those that occur later. Cleaning one body part reduces the sensory drive to its motor program, which relieves suppression of the next movement, allowing the grooming sequence to progress down the hierarchy. A model featuring independently evoked cleaning movements activated in parallel, but selected serially through hierarchical suppression, was successful in reproducing the grooming sequence. This provides the first example of an innate motor sequence implemented by the prevailing model for generating human action sequences. PMID- 25139956 TI - The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium. AB - The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anaphase-promoting complex (APC), an E3 that regulates the onset of anaphase, destabilizes axonemal microtubules in the primary cilium. Furthermore, the metaphase APC co-activator, Cdc20, is specifically recruited to the basal body of primary cilia. Inhibition of APC-Cdc20 activity increases the ciliary length, while overexpression of Cdc20 suppresses cilium formation. APC-Cdc20 activity is required for the timely resorption of the cilium after serum stimulation. In addition, APC regulates the stability of axonemal microtubules through targeting Nek1, the ciliary kinase, for proteolysis. These data demonstrate a novel function of APC beyond cell cycle control and implicate critical role of ubiquitin-mediated proteolysis in ciliary disassembly. PMID- 25139957 TI - Taking a new look at how flies learn. AB - Learning based on what a fruit fly sees or what it smells might not involve distinct parts of the brain, as was previously thought. PMID- 25139958 TI - What can fruit flies teach us about karate? AB - Understanding the logic behind how a fruit fly's brain tells it to groom its body parts in a stereotyped order might help us understand other behaviours that also involve a series of actions. PMID- 25139959 TI - A pilot study of quantitative capillary refill time to identify high blood lactate levels in critically ill patients. AB - INTRODUCTION: We developed a new device to quantify capillary refill time (CRT) by applying the pulse oximeter principle, and evaluated the correlation between quantitative CRT (Q-CRT) and hypoperfusion status, as represented by blood lactate levels, in critically ill patients. METHODS: A pilot study was undertaken in the intensive care unit (ICU) in a tertiary emergency medical centre. While the pulse oxygen saturation sensor was placed on the finger of the patients, transmitted light intensity (TLI) was measured with a pulse oximeter (OLV-3100; Nihon Kohden, Tokyo, Japan) before and during compression of the finger. Q-CRT was defined as the interval from the release of compression to the time when TLI reached 90% of baseline. RESULTS: Q-CRT was analysed in a total of 57 waveforms among 23 patients and statistically correlated with lactate levels (Spearman's rank correlation coefficient, 0.681; p<0.001). The cut-off value of Q-CRT for predicting a lactate level of >=2.0 mmol/L was 6.81 s (area under the curve (AUC) (95% CI 1.000 (1.000 to 1.000), p<0.001), and the value for predicting a lactate level of >=4.0 mmol/L was 7.27 s (AUC=0.989 (95% CI 0.954 to 1.000), p<0.001). CONCLUSIONS: Q-CRT correlated with blood lactate levels in this pilot study. The most useful threshold for Q-CRT was ~6-8 s. Further study is needed to investigate the potential role of this modality as a non-invasive predictor of hypoperfusion in the emergency department, ICU and operating room settings. PMID- 25139960 TI - Diabetes and ischemic heart disease: double jeopardy with regard to depressive mood and reduced quality of life. AB - The aim of this study was to test i) whether patients having diabetes and ischemic heart disease (IHD), i.e., patients suffering from two chronic diseases, demonstrate a higher degree of chronic stress when compared with patients suffering from IHD alone, and ii) whether suffering from the two chronic diseases results in an elevation in specific elements of the chronic stress concept. A total of 361 participants with IHD were included, of whom 47 suffered from concomitant diabetes. Stress was measured by pressure pain sensitivity (PPS) and by the following questionnaires: the Major Depression Inventory (MDI), the SF-36 Quality of Life questionnaire (SF-36 QOL), the WHO-5 Well-being Index, and the clinical stress signs (CSSs) scale. Participants with diabetes and IHD had a higher MDI score, a lower SF-36 physical component summary score, and a lower score of several sub-measurements of the SF-36 mental component score when compared with patients with IHD without diabetes. No significant differences were observed regarding stress measured by the PPS measure, the WHO-5 Well-being Index, or the number of CSSs. In conclusion, the combination of diabetes and IHD seems to be associated with increased depressive symptoms, lower overall physical QOL, and reduced mental QOL on several sub-elements of the questionnaire. This should be recognized in the management of patients with double diagnoses. PMID- 25139961 TI - High usage of topical fusidic acid and rapid clonal expansion of fusidic acid resistant Staphylococcus aureus: a cautionary tale. AB - Our aim was to assess national prescribing trends and determine longitudinal resistance patterns for topical antimicrobials in New Zealand. We observed a dramatic increase in fusidic acid (FA) resistance, and clonal expansion of FA resistant Staphylococcus aureus. This increase was concurrent with a significant national increase in topical FA dispensing. PMID- 25139962 TI - Prevalence and predictors for homo- and heterosubtypic antibodies against influenza a virus. AB - BACKGROUND: The effectiveness of trivalent influenza vaccination has been confirmed in several studies. To date, it is not known whether repeated exposure and vaccination to influenza promote production of cross-reactive antibodies. Furthermore, how strains encountered earlier in life imprint the immune response is currently poorly understood. METHODS: To determine the prevalence for human homo- and heterosubtypic antibody responses, we scrutinized serum samples from 305 healthy volunteers for hemagglutinin-binding and -neutralizing antibodies against several strains and subtypes of influenza A. Statistical analyses were then performed to establish the association of measured values with potential predictors. RESULTS: It was found that vaccination not only promoted higher binding and neutralizing antibody titers to homosubtypic influenza isolates but also increased heterosubtypic human immune responses. Both binding and neutralizing antibody titers in relation with age of the donors mirrored the course of the different influenza strain circulation during the last century. Advanced age appeared to be of advantage for both binding and neutralizing titers to most subtypes. In contrast, the first virus subtype encountered was found to imprint to some degree subsequent antibody responses. Antibodies to recent strains, however, primarily seemed to be promoted by vaccination. CONCLUSIONS: We provide evidence that vaccinations stimulate both homo- and heterosubtypic immune responses in young and middle-aged as well as more senior individuals. Our analyses suggest that influenza vaccinations not only prevent infection against currently circulating strains but can also stimulate broader humoral immune responses that potentially attenuate infections with zoonotic or antigenically shifted strains. PMID- 25139964 TI - Does HIV remain a risk factor for achieving sustained virologic response under direct acting antiviral-based modern hepatitis C virus therapy? PMID- 25139963 TI - Telaprevir for HIV/hepatitis C virus-coinfected patients failing treatment with pegylated interferon/ribavirin (ANRS HC26 TelapreVIH): an open-label, single-arm, phase 2 trial. AB - BACKGROUND: Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. METHODS: HIV type 1-infected patients who previously failed >=12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 ug/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). RESULTS: Sixty nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. CONCLUSIONS: Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955. PMID- 25139965 TI - Reply to Antinori et al. PMID- 25139966 TI - Diagnosis of central nervous system mycoses in solid organ transplant recipients. PMID- 25139967 TI - Editorial commentary: Changing epidemiology of influenza B virus. PMID- 25139968 TI - Uniform research case definition criteria differentiate tuberculous and bacterial meningitis in children. AB - BACKGROUND: Tuberculous meningitis (TBM) research is hampered by low numbers of microbiologically confirmed TBM cases and the fact that they may represent a select part of the disease spectrum. A uniform TBM research case definition was developed to address these limitations, but its ability to differentiate TBM from bacterial meningitis has not been evaluated. METHODS: We assessed all children treated for TBM from 1985 to 2005 at Tygerberg Children's Hospital, Cape Town, South Africa. For comparative purposes, a group of children with culture confirmed bacterial meningitis, diagnosed between 2003 and 2009, was identified from the National Health Laboratory Service database. The performance of the proposed case definition was evaluated in culture-confirmed TBM and bacterial meningitis cases. RESULTS: Of 554 children treated for TBM, 66 (11.9%) were classified as "definite TBM," 408 (73.6%) as "probable TBM," and 72 (13.0%) as "possible TBM." "Probable TBM" criteria identified culture-confirmed TBM with a sensitivity of 86% and specificity of 100%; sensitivity was increased but specificity reduced when using "possible TBM" criteria (sensitivity 100%, specificity 56%). CONCLUSIONS: "Probable TBM" criteria accurately differentiated TBM from bacterial meningitis and could be considered for use in clinical trials; reduced sensitivity in children with early TBM (stage 1 disease) remains a concern. PMID- 25139970 TI - News feature: How to light a cosmic candle. PMID- 25139969 TI - Impact of influenza B lineage-level mismatch between trivalent seasonal influenza vaccines and circulating viruses, 1999-2012. AB - BACKGROUND: Influenza B virus strains in trivalent influenza vaccines are frequently mismatched to the circulating B strains, but the population-level impact of such mismatches is unknown. We assessed the impact of vaccine mismatch on the epidemiology of influenza B during 12 recent seasonal outbreaks of influenza in Finland. METHODS: We analyzed all available nationwide data on virologically confirmed influenza infections in all age groups in Finland between 1 July 1999 and 30 June 2012, with the exclusion of the pandemic season of 2009 2010. We derived data on influenza infections and the circulation of different lineages of B viruses during each season from the Infectious Diseases Register and the National Influenza Center, National Institute for Health and Welfare, Finland. RESULTS: A total of 34 788 cases of influenza were recorded. Influenza A accounted for 74.0% and influenza B for 26.0% of all typed viruses. Throughout the 12 seasons, we estimated that 41.7% (3750 of 8993) of all influenza B infections were caused by viruses representing the other genetic lineage than the one in the vaccine. Altogether, opposite-lineage influenza B viruses accounted for 10.8% of all influenza infections in the population, the proportion being highest (16.8%) in children aged 10-14 years and lowest (2.6%) in persons aged >=70 years. CONCLUSIONS: The population-level impact of lineage-level mismatch between the vaccine and circulating strains of influenza B viruses is substantial, especially among children and adolescents. The results provide strong support for the inclusion of both influenza B lineages in seasonal influenza vaccines. PMID- 25139972 TI - Cleaning up the record on the maximal information coefficient and equitability. PMID- 25139973 TI - A pending issue: an analysis of health promotion research in Latin America. PMID- 25139980 TI - For bats and dolphins, hearing gene prestin adapted for echolocation. PMID- 25139979 TI - Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: A Double Blinded, Randomized Placebo-Controlled Pilot Study in Critically Ill Neonates. AB - BACKGROUND: This study's objective was to determine if parenteral cysteine when compared with isonitrogenous noncysteine supplementation increases erythrocyte reduced glutathione (GSH) in neonates at high risk for inflammatory injury. MATERIAL AND METHODS: Neonates with a score for neonatal acute physiology >10 requiring mechanical ventilation and parenteral nutrition (PN) were randomized in a double-blinded, placebo-controlled study to receive parenteral cysteine-HCl (CYS group) or additional PN amino acids (ISO group) at 121 mg/kg/d for >=7 days. A 6-hour [(13)C2] glycine IV infusion was administered at study week 1 to determine the fractional synthetic rate of GSH (FSR-GSH). RESULTS: Baseline characteristics were similar between the CYS (n = 17) and ISO groups (n = 21). Erythrocyte GSH and total glutathione concentrations, GSH:oxidized GSH (GSSG), and FSR-GSH after treatment were not different between groups. However, the CYS group had a larger individual positive change in GSH and total glutathione (infusion day - baseline) compared with the ISO group (P = .02 for each). After adjusting for treatment, a lower enrollment weight and rate of red blood cell transfusion were associated with a decreased change in total glutathione and GSH (P < .05 for each). CONCLUSION: When compared with isonitrogenous noncysteine supplementation, high-dose cysteine supplementation for at least 1 week in critically ill neonates resulted in a larger and more positive individual change in GSH. Smaller infants and those who received transfused blood demonstrated less effective change in GSH with cysteine supplementation. The benefit of cysteine remains promising and deserves further investigation. PMID- 25139985 TI - Experimental basis for a new allosteric model for multisubunit proteins. AB - Monod, Wyman, and Changeux (MWC) explained allostery in multisubunit proteins with a widely applied theoretical model in which binding of small molecules, so called allosteric effectors, affects reactivity by altering the equilibrium between more reactive (R) and less reactive (T) quaternary structures. In their model, each quaternary structure has a single reactivity. Here, we use silica gels to trap protein conformations and a new kind of laser photolysis experiment to show that hemoglobin, the paradigm of allostery, exhibits two ligand binding phases with the same fast and slow rates in both R and T quaternary structures. Allosteric effectors change the fraction of each phase but not the rates. These surprising results are readily explained by the simplest possible extension of the MWC model to include a preequilibrium between two tertiary conformations that have the same functional properties within each quaternary structure. They also have important implications for the long-standing question of a structural explanation for the difference in hemoglobin oxygen affinity of the two quaternary structures. PMID- 25139986 TI - Phospholipase A2 regulates eicosanoid class switching during inflammasome activation. AB - Initiation and resolution of inflammation are considered to be tightly connected processes. Lipoxins (LX) are proresolution lipid mediators that inhibit phlogistic neutrophil recruitment and promote wound-healing macrophage recruitment in humans via potent and specific signaling through the LXA4 receptor (ALX). One model of lipoxin biosynthesis involves sequential metabolism of arachidonic acid by two cell types expressing a combined transcellular metabolon. It is currently unclear how lipoxins are efficiently formed from precursors or if they are directly generated after receptor-mediated inflammatory commitment. Here, we provide evidence for a pathway by which lipoxins are generated in macrophages as a consequence of sequential activation of toll-like receptor 4 (TLR4), a receptor for endotoxin, and P2X7, a purinergic receptor for extracellular ATP. Initial activation of TLR4 results in accumulation of the cyclooxygenase-2-derived lipoxin precursor 15-hydroxyeicosatetraenoic acid (15 HETE) in esterified form within membrane phospholipids, which can be enhanced by aspirin (ASA) treatment. Subsequent activation of P2X7 results in efficient hydrolysis of 15-HETE from membrane phospholipids by group IVA cytosolic phospholipase A2, and its conversion to bioactive lipoxins by 5-lipoxygenase. Our results demonstrate how a single immune cell can store a proresolving lipid precursor and then release it for bioactive maturation and secretion, conceptually similar to the production and inflammasome-dependent maturation of the proinflammatory IL-1 family cytokines. These findings provide evidence for receptor-specific and combinatorial control of pro- and anti-inflammatory eicosanoid biosynthesis, and potential avenues to modulate inflammatory indices without inhibiting downstream eicosanoid pathways. PMID- 25139987 TI - Efficient utilization of complex N-linked glycans is a selective advantage for Bacteroides fragilis in extraintestinal infections. AB - Bacteroides fragilis is the most common anaerobe isolated from clinical infections, and in this report we demonstrate a characteristic of the species that is critical to their success as an opportunistic pathogen. Among the Bacteroides spp. in the gut, B. fragilis has the unique ability of efficiently harvesting complex N-linked glycans from the glycoproteins common to serum and serous fluid. This activity is mediated by an outer membrane protein complex designated as Don. Using the abundant serum glycoprotein transferrin as a model, it has been shown that B. fragilis alone can rapidly and efficiently deglycosylate this protein in vitro and that transferrin glycans can provide the sole source of carbon and energy for growth in defined media. We then showed that transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the rat tissue cage model of extraintestinal growth, and that this ability provides a competitive advantage in vivo over strains lacking the don locus. PMID- 25139988 TI - Assembly and dynamics of the autophagy-initiating Atg1 complex. AB - The autophagy-related 1 (Atg1) complex of Saccharomyces cerevisiae has a central role in the initiation of autophagy following starvation and TORC1 inactivation. The complex consists of the protein kinase Atg1, the TORC1 substrate Atg13, and the trimeric Atg17-Atg31-Atg29 scaffolding subcomplex. Autophagy is triggered when Atg1 and Atg13 assemble with the trimeric scaffold. Here we show by hydrogen deuterium exchange coupled to mass spectrometry that the mutually interacting Atg1 early autophagy targeting/tethering domain and the Atg13 central domain are highly dynamic in isolation but together form a stable complex with ~ 100-nM affinity. The Atg1-Atg13 complex in turn binds as a unit to the Atg17-Atg31-Atg29 scaffold with ~ 10-MUM affinity via Atg13. The resulting complex consists primarily of a dimer of pentamers in solution. These results lead to a model for autophagy initiation in which Atg1 and Atg13 are tightly associated with one another and assemble transiently into the pentameric Atg1 complex during starvation. PMID- 25139989 TI - Bioinformatic analysis reveals a pattern of STAT3-associated gene expression specific to basal-like breast cancers in human tumors. AB - Signal transducer and activator of transcription 3 (STAT3), a latent transcription factor associated with inflammatory signaling and innate and adaptive immune responses, is known to be aberrantly activated in a wide variety of cancers. In vitro analysis of STAT3 in human cancer cell lines has elucidated a number of specific targets associated with poor prognosis in breast cancer. However, to date, no comparison of cancer subtype and gene expression associated with STAT3 signaling in human patients has been reported. In silico analysis of human breast cancer microarray and reverse-phase protein array data was performed to identify expression patterns associated with STAT3 in basal-like and luminal breast cancers. Results indicate clearly identifiable STAT3-regulated signatures common to basal-like breast cancers but not to luminal A or luminal B cancers. Furthermore, these differentially expressed genes are associated with immune signaling and inflammation, a known phenotype of basal-like cancers. These findings demonstrate a distinct role for STAT3 signaling in basal breast cancers, and underscore the importance of considering subtype-specific molecular pathways that contribute to tissue-specific cancers. PMID- 25139990 TI - Immunolocalization of skeletal matrix proteins in tissue and mineral of the coral Stylophora pistillata. AB - The precipitation and assembly of calcium carbonate skeletons by stony corals is a precisely controlled process regulated by the secretion of an ECM. Recently, it has been reported that the proteome of the skeletal organic matrix (SOM) contains a group of coral acid-rich proteins as well as an assemblage of adhesion and structural proteins, which together, create a framework for the precipitation of aragonite. To date, we are aware of no report that has investigated the localization of individual SOM proteins in the skeleton. In particular, no data are available on the ultrastructural mapping of these proteins in the calcification site or the skeleton. This information is crucial to assessing the role of these proteins in biomineralization. Immunological techniques represent a valuable approach to localize a single component within a calcified skeleton. By using immunogold labeling and immunohistochemical assays, here we show the spatial arrangement of key matrix proteins in tissue and skeleton of the common zooxanthellate coral, Stylophora pistillata. To our knowledge, our results reveal for the first time that, at the nanoscale, skeletal proteins are embedded within the aragonite crystals in a highly ordered arrangement consistent with a diel calcification pattern. In the tissue, these proteins are not restricted to the calcifying epithelium, suggesting that they also play other roles in the coral's metabolic pathways. PMID- 25139991 TI - Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis. AB - Endothelial cells (ECs) express fibroblast growth factor receptors (FGFRs) and are exquisitely sensitive to FGF signals. However, whether the EC or another vascular cell type requires FGF signaling during development, homeostasis, and response to injury is not known. Here, we show that Flk1-Cre or Tie2-Cre mediated deletion of FGFR1 and FGFR2 (Fgfr1/2(Flk1-Cre) or Fgfr1/2(Tie2-Cre) mice), which results in deletion in endothelial and hematopoietic cells, is compatible with normal embryonic development. As adults, Fgfr1/2(Flk1-Cre) mice maintain normal blood pressure and vascular reactivity and integrity under homeostatic conditions. However, neovascularization after skin or eye injury was significantly impaired in both Fgfr1/2(Flk1-Cre) and Fgfr1/2(Tie2-Cre) mice, independent of either hematopoietic cell loss of FGFR1/2 or vascular endothelial growth factor receptor 2 (Vegfr2) haploinsufficiency. Also, impaired neovascularization was associated with delayed cutaneous wound healing. These findings reveal a key requirement for cell-autonomous EC FGFR signaling in injury induced angiogenesis, but not for vascular homeostasis, identifying the EC FGFR signaling pathway as a target for diseases associated with aberrant vascular proliferation, such as age-related macular degeneration, and for modulating wound healing without the potential toxicity associated with direct manipulation of systemic FGF or VEGF activity. PMID- 25139992 TI - Interlamellar CA1 network in the hippocampus. AB - To understand the cellular basis of learning and memory, the neurophysiology of the hippocampus has been largely examined in thin transverse slice preparations. However, the synaptic architecture along the longitudinal septo-temporal axis perpendicular to the transverse projections in CA1 is largely unknown, despite its potential significance for understanding the information processing carried out by the hippocampus. Here, using a battery of powerful techniques, including 3D digital holography and focal glutamate uncaging, voltage-sensitive dye, two photon imaging, electrophysiology, and immunohistochemistry, we show that CA1 pyramidal neurons are connected to one another in an associational and well organized fashion along the longitudinal axis of the hippocampus. Such CA1 longitudinal connections mediate reliable signal transfer among the pyramidal cells and express significant synaptic plasticity. These results illustrate a need to reconceptualize hippocampal CA1 network function to include not only processing in the transverse plane, but also operations made possible by the longitudinal network. Our data will thus provide an essential basis for future computational modeling studies on information processing operations carried out in the full 3D hippocampal network that underlies its complex cognitive functions. PMID- 25139993 TI - Targeted gene knockout in chickens mediated by TALENs. AB - Genetically modified animals are used for industrial applications as well as scientific research, and studies on these animals contribute to a better understanding of biological mechanisms. Gene targeting techniques have been developed to edit specific gene loci in the genome, but the conventional strategy of homologous recombination with a gene-targeted vector has low efficiency and many technical complications. Here, we generated specific gene knockout chickens through the use of transcription activator-like effector nuclease (TALEN) mediated gene targeting. In this study, we accomplished targeted knockout of the ovalbumin (OV) gene in the chicken primordial germ cells, and OV gene mutant offspring were generated through test-cross analysis. TALENs successfully induced nucleotide deletion mutations of ORF shifts, resulting in loss of chicken OV gene function. Our results demonstrate that the TALEN technique used in the chicken primordial germ cell line is a powerful strategy to create specific genome-edited chickens safely for practical applications. PMID- 25139994 TI - Roles of cGMP-dependent protein kinase I (cGKI) and PDE5 in the regulation of Ang II-induced cardiac hypertrophy and fibrosis. AB - Conflicting results have been reported for the roles of cGMP and cGMP-dependent protein kinase I (cGKI) in various pathological conditions leading to cardiac hypertrophy and fibrosis. A cardioprotective effect of cGMP/cGKI has been reported in whole animals and isolated cardiomyocytes, but recent evidence from a mouse model expressing cGKIbeta only in smooth muscle (betaRM) but not in cardiomyocytes, endothelial cells, or fibroblasts has forced a reevaluation of the requirement for cGKI activity in the cardiomyocyte antihypertrophic effects of cGMP. In particular, betaRM mice developed the same hypertrophy as WT controls when subjected to thoracic aortic constriction or isoproterenol infusion. Here, we challenged betaRM and WT (Ctr) littermate control mice with angiotensin II (AII) infusion (7 d; 2 mg ? kg(-1) ? d(-1)) to induce hypertrophy. Both genotypes developed cardiac hypertrophy, which was more pronounced in Ctr animals. Cardiomyocyte size and interstitial fibrosis were increased equally in both genotypes. Addition of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, in the drinking water had a small effect in reducing myocyte hypertrophy in WT mice and no effect in betaRM mice. However, sildenafil substantially blocked the increase in collagen I, fibronectin 1, TGFbeta, and CTGF mRNA in Ctr but not in betaRM hearts. These data indicate that, for the initial phase of AII-induced cardiac hypertrophy, lack of cardiomyocyte cGKI activity does not worsen hypertrophic growth. However, expression of cGKI in one or more cell types other than smooth muscle is necessary to allow the antifibrotic effect of sildenafil. PMID- 25139995 TI - Reconstruction and minimal gene requirements for the alternative iron-only nitrogenase in Escherichia coli. AB - All diazotrophic organisms sequenced to date encode a molybdenum-dependent nitrogenase, but some also have alternative nitrogenases that are dependent on either vanadium (VFe) or iron only (FeFe) for activity. In Azotobacter vinelandii, expression of the three different types of nitrogenase is regulated in response to metal availability. The majority of genes required for nitrogen fixation in this organism are encoded in the nitrogen fixation (nif) gene clusters, whereas genes specific for vanadium- or iron-dependent diazotophy are encoded by the vanadium nitrogen fixation (vnf) and alternative nitrogen fixation (anf) genes, respectively. Due to the complexities of metal-dependent regulation and gene redundancy in A. vinelandii, it has been difficult to determine the precise genetic requirements for alternative nitrogen fixation. In this study, we have used Escherichia coli as a chassis to build an artificial iron-only (Anf) nitrogenase system composed of defined anf and nif genes. Using this system, we demonstrate that the pathway for biosynthesis of the iron-only cofactor (FeFe-co) is likely to be simpler than the pathway for biosynthesis of the molybdenum dependent cofactor (FeMo-co) equivalent. A number of genes considered to be essential for nitrogen fixation by FeFe nitrogenase, including nifM, vnfEN, and anfOR, are not required for the artificial Anf system in E. coli. This finding has enabled us to engineer a minimal FeFe nitrogenase system comprising the structural anfHDGK genes and the nifBUSV genes required for metallocluster biosynthesis, with nifF and nifJ providing electron transport to the alternative nitrogenase. This minimal Anf system has potential implications for engineering diazotrophy in eukaryotes, particularly in compartments (e.g., organelles) where molybdenum may be limiting. PMID- 25139996 TI - Nedd9 restrains renal cystogenesis in Pkd1-/- mice. AB - Mutations inactivating the cilia-localized Pkd1 protein result in autosomal dominant polycystic kidney disease (ADPKD), a serious inherited syndrome affecting ~ 1 in 500 people, in which accumulation of renal cysts eventually destroys kidney function. Severity of ADPKD varies throughout the population, for reasons thought to involve differences both in intragenic Pkd1 mutations and in modifier alleles. The scaffolding protein NEDD9, commonly dysregulated during cancer progression, interacts with Aurora-A (AURKA) kinase to control ciliary resorption, and with Src and other partners to influence proliferative signaling pathways often activated in ADPKD. We here demonstrate Nedd9 expression is deregulated in human ADPKD and a mouse ADPKD model. Although genetic ablation of Nedd9 does not independently influence cystogenesis, constitutive absence of Nedd9 strongly promotes cyst formation in the tamoxifen-inducible Pkd1fl/fl;Cre/Esr1(+) mouse model of ADPKD. This cystogenic effect is associated with striking morphological defects in the cilia of Pkd1(-/-);Nedd9(-/-) mice, associated with specific loss of ciliary localization of adenylase cyclase III in the doubly mutant genotype. Ciliary phenotypes imply a failure of Aurora-A activation: Compatible with this idea, Pkd1(-/-);Nedd9(-/-) mice had ciliary resorption defects, and treatment of Pkd1(-/-) mice with a clinical Aurora-A kinase inhibitor exacerbated cystogenesis. In addition, activation of the ADPKD associated signaling effectors Src, Erk, and the mTOR effector S6 was enhanced, and Ca(2+) response to external stimuli was reduced, in Pkd1(-/-);Nedd9(-/-) versus Pkd1(-/-) mice. Together, these results indicated an important modifier action of Nedd9 on ADPKD pathogenesis involving failure to activate Aurora-A. PMID- 25139997 TI - Refilling drug delivery depots through the blood. AB - Local drug delivery depots have significant clinical utility, but there is currently no noninvasive technique to refill these systems once their payload is exhausted. Inspired by the ability of nanotherapeutics to target specific tissues, we hypothesized that blood-borne drug payloads could be modified to home to and refill hydrogel drug delivery systems. To address this possibility, hydrogels were modified with oligodeoxynucleotides (ODNs) that provide a target for drug payloads in the form of free alginate strands carrying complementary ODNs. Coupling ODNs to alginate strands led to specific binding to complementary ODN-carrying alginate gels in vitro and to injected gels in vivo. When coupled to a drug payload, sequence-targeted refilling of a delivery depot consisting of intratumor hydrogels completely abrogated tumor growth. These results suggest a new paradigm for nanotherapeutic drug delivery, and this concept is expected to have applications in refilling drug depots in cancer therapy, wound healing, and drug-eluting vascular grafts and stents. PMID- 25139999 TI - Axl kinase as a key target for oncology: focus on small molecule inhibitors. AB - Receptor tyrosine kinases (RTK) are transmembrane receptors that regulate signal transduction in cells. As a member of the TAM (Tyro-3, Axl, Mer) RTK subfamily, Axl regulates key processes such as cell growth, migration, aggregation, and apoptosis through several pathways. Its overexpression/overactivation has been underlined in several conditions, especially cancers, and in both chemotherapy and targeted therapy sensitivity loss. In this review, we propose to highlight the therapeutic implication of Axl, starting with the pathways it regulates, validating its interest as a therapeutic target, and defining the tools available to develop strategies for its inhibition. We especially focus on small molecule inhibitors, their structure, inhibition profile, and development stages. PMID- 25139998 TI - Annexin 2-CXCL12 interactions regulate metastatic cell targeting and growth in the bone marrow. AB - Annexin 2 (ANXA2) plays a critical role in hematopoietic stem cell (HSC) localization to the marrow niche. In part, ANXA2 supports HSCs by serving as an anchor for stromal-derived factor-1 (CXCL12/SDF-1). Recently, it was demonstrated that prostate cancer cells, like HSCs, use ANXA2 to establish metastases in marrow. The present study determined the capacity of ANXA2 expression by bone marrow stromal cells (BMSC) to facilitate tumor recruitment and growth through ANXA2-CXCL12 interactions. Significantly more CXCL12 was expressed by BMSC(Anxa2) (+/+) than by BMSC(Anxa2) (-/-) resulting in more prostate cancer cells migrating and binding to BMSC(Anxa2) (+/+) than BMSC(Anxa2) (-/-), and these activities were reduced when CXCL12 interactions were blocked. To further confirm that BMSC signaling through ANXA2-CXCL12 plays a critical role in tumor growth, immunocompromised SCID mice were subcutaneously implanted with human prostate cancer cells mixed with BMSC(Anxa2) (+/+) or BMSC(Anxa2) (-/-). Significantly larger tumors grew in the mice when the tumors were established with BMSC(Anxa2) (+/+) compared with the tumors established with BMSC(Anxa2) (-/-). In addition, fewer prostate cancer cells underwent apoptosis when cocultured with BMSC(Anxa2) (+/+) compared with BMSC(Anxa2) (-/-), and similar results were obtained in tumors grown in vivo. Finally, significantly more vascular structures were observed in the tumors established with the BMSC(Anxa2) (+/+) compared with the tumors established with BMSC(Anxa2) (-/-). Thus, ANXA2-CXCL12 interactions play a crucial role in the recruitment, growth, and survival of prostate cancer cells in the marrow. IMPLICATIONS: The tumor microenvironment interaction between ANXA2 CXCL12 is critical for metastatic phenotypes and may impact chemotherapeutic potential. PMID- 25140000 TI - Epidermal growth factor-like domain 7 predicts response to first-line chemotherapy and bevacizumab in patients with metastatic colorectal cancer. AB - The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA 126 (miR126) to first-line chemotherapy combined with bevacizumab, in patients with metastatic colorectal cancer (mCRC). A total of 158 patients from two different, but comparable, cohorts were included. Analyses were performed on tumor tissue from the primary tumor either based on a whole-tumor resection or an endoscopic biopsy. EGFL7 was analyzed by immunohistochemistry (IHC) and miR126 by in situ hybridization (ISH). Both biomarkers were quantified by image-guided analyses. Endpoints were response rate (RR) and progression-free survival (PFS). The EGFL7 vessel area (VA) in tumor resections was closely related to treatment response with a median EGFL7 VA in responding patients of 4 [95% confidence interval (CI), 4-6] compared with 8.5 (95% CI, 7-11) in nonresponders, P = 0.0008. This difference translated into a borderline significant difference in PFS (P = 0.06). Furthermore, a significant relationship between high EGFL7 VA and KRAS mutation was detected (P = 0.049). The results showed no significant relationship between the miR126 VA and the clinical endpoints. Our study suggests a predictive value of EGFL7 in regard to first-line chemotherapy and bevacizumab in patients with mCRC and supports the mechanism of a dual blocking of the vascular endothelial growth factor-A and EGFL7 axis in this setting. PMID- 25140001 TI - The effect of conditioned medium derived from human placental multipotent mesenchymal stromal cells on neutrophils: possible implications for placental infection. AB - The role of human placental multipotent mesenchymal stromal cells (hPMSCs) in placental inflammation is unknown. We hypothesize that hPMSCs are involved in the early phases of placental infection. hPMSCs were isolated from term placentas and neutrophils from peripheral blood. The expression of toll-like receptors (TLRs) and cytokines by hPMSCs was determined by RT-PCR, flow cytometry and enzyme linked immunosorbent assay. The effect of conditioned medium of hPMSCs with or without lipopolysaccharide (LPS) pretreatment on neutrophil functions: migration, apoptosis and production of reactive oxygen species (ROS) was assessed by flow cytometry and western blot. hPMSCs expressed TLR1, TLR3, TLR4, TLR6, TLR7 and TLR9. LPS stimulation increased the expression of TLR4 and the production of IL-6 and IL-8 by hPMSCs. Neutrophils exhibited chemotaxis to hPMSC-conditioned medium, which was inhibited by IL-8 depletion. Neutrophil CD11b activation was promoted by hPMSC-conditioned medium, which was further enhanced in media from hPMSCs pretreated with LPS. hPMSC-conditioned medium reduced neutrophil ROS production. Neutrophil phagocytosis was increased by LPS alone but not by hPMSC-conditioned medium with or without LPS stimulation. hPMSC-conditioned medium induced STAT3 activation in neutrophils, which was inhibited by neutralizing antibody to IL-6. hPMSC-conditioned medium rescued neutrophils from apoptosis, but this effect was significantly reduced in conditioned medium of hPMSCs with LPS pretreatment. Depletion of IL-6 from the conditioned medium further inhibited the anti apoptotic effect on neutrophils. Our results demonstrate that hPMSCs can interact with peripheral blood neutrophils in response to inflammatory signals of the placenta. Cytokines produced by hPMSCs can induce neutrophil chemotaxis and reduce neutrophil apoptosis. PMID- 25140002 TI - Clemizole hydrochloride is a novel and potent inhibitor of transient receptor potential channel TRPC5. AB - Canonical transient receptor potential channel 5 (TRPC5) is a nonselective, Ca(2+)-permeable cation channel that belongs to the large family of transient receptor potential channels. It is predominantly found in the central nervous system with a high expression density in the hippocampus, the amygdala, and the frontal cortex. Several studies confirm that TRPC5 channels are implicated in the regulation of neurite length and growth cone morphology. We identified clemizole as a novel inhibitor of TRPC5 channels. Clemizole efficiently blocks TRPC5 currents and Ca(2+) entry in the low micromolar range (IC50 = 1.0-1.3 uM), as determined by fluorometric intracellular free Ca(2+) concentration ([Ca(2+)]i) measurements and patch-clamp recordings. Clemizole blocks TRPC5 currents irrespectively of the mode of activation, for example, stimulation of G protein coupled receptors, hypo-osmotic buffer conditions, or by the direct activator riluzole. Electrophysiological whole-cell recordings revealed that the block was mostly reversible. Moreover, clemizole was still effective in blocking TRPC5 single channels in excised inside-out membrane patches, hinting to a direct block of TRPC5 by clemizole. Based on fluorometric [Ca(2+)]i measurements, clemizole exhibits a sixfold selectivity for TRPC5 over TRPC4beta (IC50 = 6.4 uM), the closest structural relative of TRPC5, and an almost 10-fold selectivity over TRPC3 (IC50 = 9.1 uM) and TRPC6 (IC50 = 11.3 uM). TRPM3 and M8 as well as TRPV1, V2, V3, and V4 channels were only weakly affected by markedly higher clemizole concentrations. Clemizole was not only effective in blocking heterologously expressed TRPC5 homomers but also TRPC1:TRPC5 heteromers as well as native TRPC5 like currents in the U-87 glioblastoma cell line. PMID- 25140004 TI - Novel oral anticoagulants: too good to be true? PMID- 25140003 TI - Robust hydrolysis of prostaglandin glycerol esters by human monoacylglycerol lipase (MAGL). AB - The primary route of inactivation of the endocannabinoid 2-arachidonoylglycerol in the central nervous system is through enzymatic hydrolysis, mainly carried out by monoacylglycerol lipase (MAGL), along with a small contribution by the alpha/beta-hydrolase domain (ABHD) proteins ABHD6 and ABHD12. Recent methodological progress allowing kinetic monitoring of glycerol liberation has facilitated substrate profiling of the human endocannabinoid hydrolases, and these studies have revealed that the three enzymes have distinct monoacylglycerol substrate and isomer preferences. Here, we have extended this substrate profiling to cover four prostaglandin glycerol esters, namely, 15-deoxy-Delta(12,14) prostaglandin J2-2-glycerol (15d-PGJ2-G), PGD2-G, PGE2-G, and PGF2 alpha-G. We found that the three enzymes hydrolyzed the tested substrates, albeit with distinct rates and preferences. Although human ABHD12 (hABHD12) showed only marginal activity toward PGE2-G, hABHD6 preferentially hydrolyzed PGD2-G, and human MAGL (hMAGL) robustly hydrolyzed all four. This was particularly intriguing for MAGL activity toward 15d-PGJ2-G whose hydrolysis rate rivaled that of the best monoacylglycerol substrates. Molecular modeling studies combined with kinetic analysis supported favorable interaction with the hMAGL active site. Long and short MAGL isoforms shared a similar substrate profile, and hMAGL hydrolyzed 15d-PGJ2-G also in living cells. The ability of 15d-PGJ2-G to activate the canonical nuclear factor erythroid 2-related factor (Nrf2) signaling pathway used by 15d-PGJ2 was assessed, and these studies revealed for the first time that 15d PGJ2 and 15d-PGJ2-G similarly activated Nrf2 signaling as well as transcription of target genes of this pathway. Our study challenges previous claims regarding the ability of MAGL to catalyze PG-G hydrolysis and extend the MAGL substrate profile beyond the classic monoacylglycerols. PMID- 25140005 TI - Patient-centered medical home: the future of healthcare delivery? PMID- 25140006 TI - Republished: creating a safe, reliable hospital at night handover: a case study in implementation science. AB - BACKGROUND: We developed protocols to handover patients from day to hospital at night (H@N) teams. SETTING: NHS paediatric specialist hospital. METHOD: We observed four handover protocols (baseline, Phases 1, 2 and 3) over 2 years. A mixed-method study (observation, interviews, task analysis, prospective risk assessment, document and case note review) explored the impact of different protocols on performance. INTERVENTION: In Phase 1, a handover protocol was introduced to resolve problems with the baseline H@N handover. Following this intervention, two further revisions to the handover occurred, driven by staff feedback (Phases 2 and 3). RESULTS: Variations in performance between handover protocols on three process measures, start time efficiency, total length of handover, and number of distractions and interruptions, were identified. Univariate regression analysis showed statistically significant differences between handover protocols on two surrogate outcome measures: number of flagging omissions and the number of out of hours deteriorations (p=0.04 for Phase 3 vs Phase 1 for both measures (CI 1.04 to 4.08; CI 1.03 to 4.33), and for Phase 3 vs Phase 2 (p=0.006 and p=0.001 (CI 1.22 to 5.15; CI 1.62 to 9.0)), respectively). The Phase 1 and 2 handover protocols were effective at identifying patients whose clinical condition warranted review overnight. Performance on both surrogate outcome measures, length of handover and distractions, deteriorated in Phase 3. CONCLUSIONS: A carefully designed prioritisation process within the H@N handover can be effective at flagging acutely unwell patients. However, the protocol we introduced was unsustainable. In a complex healthcare system, sustainable implementation of new processes may be threatened by conflicting goals. PMID- 25140007 TI - Republished: clinical implications of the third universal definition of myocardial infarction. PMID- 25140008 TI - Of human bondage. PMID- 25140009 TI - A competitive formation of DNA:RNA hybrid G-quadruplex is responsible to the mitochondrial transcription termination at the DNA replication priming site. AB - Human mitochondrial DNA contains a distinctive guanine-rich motif denoted conserved sequence block II (CSB II) that stops RNA transcription, producing prematurely terminated transcripts to prime mitochondrial DNA replication. Recently, we reported a general phenomenon that DNA:RNA hybrid G-quadruplexes (HQs) readily form during transcription when the non-template DNA strand is guanine-rich and such HQs in turn regulate transcription. In this work, we show that transcription of mitochondrial DNA leads to the formation of a stable HQ or alternatively an unstable intramolecular DNA G-quadruplex (DQ) at the CSB II. The HQ is the dominant species and contributes to the majority of the premature transcription termination. Manipulating the stability of the DQ has little effect on the termination even in the absence of HQ; however, abolishing the formation of HQs by preventing the participation of either DNA or RNA abolishes the vast majority of the termination. These results demonstrate that the type of G quadruplexes (HQ or DQ) is a crucial determinant in directing the transcription termination at the CSB II and suggest a potential functionality of the co transcriptionally formed HQ in DNA replication initiation. They also suggest that the competition/conversion between an HQ and a DQ may regulate the function of a G-quadruplex-forming sequence. PMID- 25140010 TI - Invincible DNA tethers: covalent DNA anchoring for enhanced temporal and force stability in magnetic tweezers experiments. AB - Magnetic tweezers are a powerful single-molecule technique that allows real-time quantitative investigation of biomolecular processes under applied force. High pulling forces exceeding tens of picoNewtons may be required, e.g. to probe the force range of proteins that actively transcribe or package the genome. Frequently, however, the application of such forces decreases the sample lifetime, hindering data acquisition. To provide experimentally viable sample lifetimes in the face of high pulling forces, we have designed a novel anchoring strategy for DNA in magnetic tweezers. Our approach, which exploits covalent functionalization based on heterobifunctional poly(ethylene glycol) crosslinkers, allows us to strongly tether DNA while simultaneously suppressing undesirable non specific adhesion. A complete force and lifetime characterization of these covalently anchored DNA-tethers demonstrates that, compared to more commonly employed anchoring strategies, they withstand 3-fold higher pulling forces (up to 150 pN) and exhibit up to 200-fold higher lifetimes (exceeding 24 h at a constant force of 150 pN). This advance makes it possible to apply the full range of biologically relevant force scales to biomolecular processes, and its straightforward implementation should extend its reach to a multitude of applications in the field of single-molecule force spectroscopy. PMID- 25140011 TI - Structure analysis of free and bound states of an RNA aptamer against ribosomal protein S8 from Bacillus anthracis. AB - Several protein-targeted RNA aptamers have been identified for a variety of applications and although the affinities of numerous protein-aptamer complexes have been determined, the structural details of these complexes have not been widely explored. We examined the structural accommodation of an RNA aptamer that binds bacterial r-protein S8. The core of the primary binding site for S8 on helix 21 of 16S rRNA contains a pair of conserved base triples that mold the sugar-phosphate backbone to S8. The aptamer, which does not contain the conserved sequence motif, is specific for the rRNA binding site of S8. The protein-free RNA aptamer adopts a helical structure with multiple non-canonical base pairs. Surprisingly, binding of S8 leads to a dramatic change in the RNA conformation that restores the signature S8 recognition fold through a novel combination of nucleobase interactions. Nucleotides within the non-canonical core rearrange to create a G-(G-C) triple and a U-(A-U)-U quartet. Although native-like S8-RNA interactions are present in the aptamer-S8 complex, the topology of the aptamer RNA differs from that of the helix 21-S8 complex. This is the first example of an RNA aptamer that adopts substantially different secondary structures in the free and protein-bound states and highlights the remarkable plasticity of RNA secondary structure. PMID- 25140012 TI - The evolution of blood pressure and the rise of mankind. AB - Why is it that only human beings continuously perform acts of heroism? Looking back at our evolutionary history can offer us some potentially useful insight. This review highlights some of the major steps in our evolution-more specifically, the evolution of high blood pressure. When we were fish, the first kidney was developed to create a standardized internal 'milieu' preserving the primordial sea within us. When we conquered land as amphibians, the evolution of the lung required a low systemic blood pressure, which explains why early land vertebrates (amphibians, reptiles) are such low performers. Gaining independence from water required the evolution of an impermeable skin and a water-retaining kidney. The latter was accomplished twice with two different solutions in the two major branches of vertebrate evolution: mammals excrete nitrogenous waste products as urea, which can be utilized by the kidney as an osmotic agent to produce more concentrated urine. Dinosaurs and birds have a distinct nitrogen metabolism and excrete nitrogen as water-insoluble uric acid-therefore, their kidneys cannot use urea to concentrate as well. Instead, some birds have developed the capability to reabsorb water from their cloacae. The convergent development of a separate small circulation of the lung in mammals and birds allowed for the evolution of 'high blood-pressure animals' with better capillarization of the peripheral tissues allowing high endurance performance. Finally, we investigate why mankind outperforms any other mammal on earth and why, to this day, we continue to perform acts of heroism on our eternal quest for personal bliss. PMID- 25140013 TI - Phosphate, urea and creatinine clearances: haemodialysis adequacy assessed by weekly monitoring. AB - BACKGROUND: The specific distribution of phosphate and the control mechanisms for its plasma level makes phosphate kinetics during haemodialysis (HD) considerably different from those of urea and creatinine and makes the quantitative evaluation of adequacy of phosphate removal difficult. We propose the application of equivalent continuous clearance (ECC) as a phosphate adequacy parameter and compare it with ECC for creatinine and urea. METHODS: Three consecutive dialysis sessions were evaluated for 25 patients on maintenance HD. Concentrations of phosphate, urea and creatinine in plasma were measured every 1h during the treatment and 45 min after, and every 30 min in dialysate. ECC was calculated using the removed solute mass assessed in dialysate and weekly solute profile in plasma. Similar calculations were performed also for the midweek dialysis session only. Different versions of the reference concentration for ECC were applied. RESULTS: ECC with peak average reference concentration was 5.4 +/- 1.0 for phosphate, 7.0 +/- 1.0 for urea and 4.7 +/- 1.0 mL/min for creatinine. ECC for urea and creatinine were well correlated in contrast to the correlations of ECC for phosphate versus urea and creatinine. Midweek ECC were higher than weekly ECC, but they were well correlated for urea and creatinine, but only weakly for phosphate. CONCLUSIONS: HD adequacy monitoring for phosphate may be performed using ECC, but it is less predictable than similar indices for urea and creatinine. The values of ECC for phosphate are within the range expected for its molecular size compared with those for urea and creatinine. PMID- 25140015 TI - High-dose isoproterenol testing for diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy: is there a role? PMID- 25140014 TI - Neprilysin inhibition in chronic kidney disease. AB - Despite current practice, patients with chronic kidney disease (CKD) are at increased risk of progression to end-stage renal disease and cardiovascular events. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential to improve outcomes for patients with CKD. NEPi enhances the activity of natriuretic peptide systems leading to natriuresis, diuresis and inhibition of the renin-angiotensin system (RAS), which could act as a potentially beneficial counter-regulatory system in states of RAS activation such as chronic heart failure (HF) and CKD. Early NEPi drugs were combined with angiotensin-converting enzyme inhibitors but were associated with unacceptable rates of angioedema and, therefore, withdrawn. However, one such agent (omapatrilat) showed promise of NEP/RAS inhibition in treating CKD in animal models, producing greater reductions in proteinuria, glomerulosclerosis and tubulointerstitial fibrosis compared with isolated RAS inhibition. A new class of drug called angiotensin receptor neprilysin inhibitor (ARNi) has been developed. One such drug, LCZ696, has shown substantial benefits in trials in hypertension and HF. In CKD, HF is common due to a range of mechanisms including hypertension and structural heart disease (including left ventricular hypertrophy), suggesting that ARNi could benefit patients with CKD by both retarding the progression of CKD (hence delaying the need for renal replacement therapy) and reducing the risk of cardiovascular disease. LCZ696 is now being studied in a CKD population. PMID- 25140016 TI - The ideal end point for ablation in postinfarction ventricular tachycardia: one may not fit all. PMID- 25140017 TI - Unravelling the paradoxical effects of ganglia ablation. PMID- 25140019 TI - Ablation versus drugs: what is the best first-line therapy for paroxysmal atrial fibrillation? Antiarrhythmic drugs are outmoded and catheter ablation should be the first-line option for all patients with paroxysmal atrial fibrillation: pro. PMID- 25140018 TI - Electroporation: past and future of catheter ablation. PMID- 25140020 TI - Ablation versus drugs: what is the best first-line therapy for paroxysmal atrial fibrillation? Antiarrhythmic drugs are outmoded and catheter ablation should be the first-line option for all patients with paroxysmal atrial fibrillation: con. PMID- 25140021 TI - Postablation scar-related atrial tachycardia: turning the spotlight on P-wave analysis and window settings. PMID- 25140022 TI - Electrocardiogram mapping-reentry: final frontier? PMID- 25140023 TI - Bradycardia-dependent conduction block into pulmonary vein after isolation. PMID- 25140024 TI - Anatomic analysis of the left atrial appendage after closure with the LARIAT device. PMID- 25140025 TI - Inappropriate shocks due to subcutaneous air in a patient with a subcutaneous cardiac defibrillator. PMID- 25140026 TI - Is medical research in danger of suffering the same fate as the NHS? PMID- 25140027 TI - Scleral granuloma revealing intraocular foreign body. PMID- 25140028 TI - An unusual cause of gastrointestinal bleeding-migration of a hip prosthesis. PMID- 25140029 TI - Bodybuilding, exogenous testosterone use and myocardial infarction. PMID- 25140030 TI - End-stage renal disease and survival in people with diabetes: a national database linkage study. AB - BACKGROUND: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). AIM: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival. METHODS: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression. RESULTS: Point prevalence of chronic kidney disease (CKD)5 in 2008 was 1.63% of 19 414 people with type 1 diabetes (T1DM) compared with 0.58% of 167 871 people with type 2 diabetes (T2DM) (odds ratio for DM type 0.97, P = 0.77, on adjustment for duration. Although 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (odds ratio for DM type 0.83, P = 0.432). Diabetic nephropathy was the primary renal diagnosis in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI: 1.92, 2.38) in T2DM. CONCLUSION: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning. PMID- 25140031 TI - Improved outcomes of high-risk emergency medical admissions cared for by experienced physicians. AB - BACKGROUND: Physician experience has been shown to improve clinical outcomes. Limited numbers of experienced clinicians make it unfeasible that they would care for all patients. We hypothesized that physician experience would impact outcomes for patients with high, but not low, risk of mortality. METHODS: All emergency admissions from 2002 to 2013 were studied. Two groups at low and high risk for mortality (1.3% (95% CI: 1.13, 1.62) vs. 19.4% (95% CI: 18.5, 20.3)) were defined by a risk prediction method comprising acute Illness Severity Score, Charlson Comorbidity Index and sepsis status. Length of stay (LOS) and 30-day in-hospital mortality were the primary end points. Consultant experience was studied univariately and also entered into a multiple logistic regression model to predict 30-day in-hospital survival. A zero-truncated Poisson regression model assessed LOS and incidence rate ratios (IRR) were calculated. RESULTS: Over the 12-year study period 66 933 admissions were recorded in 36 271 patients. High risk patients cared for by more experienced (>=20 years qualified) physicians had a lower 30-day in-hospital mortality (19.4 vs. 17.1% P < 0.001), relative risk reduction 11.9%. The multivariable odds ratio of a 30-day in-hospital death for an experienced physician was 0.89 (95% CI: 0.82, 0.97; P = 0.009). LOS was shorter for high-risk patients allocated to experienced physicians with a multivariable IRR of 0.77 (95% CI: 0.94, 0.99; P = 0.02). No difference in outcomes was found for low-risk patients. CONCLUSION: High-risk but not low-risk patients have improved outcomes when cared for by physicians with greater experience. PMID- 25140032 TI - Effects of an educational intervention of physical activity for children and adolescents with cystic fibrosis: a randomized controlled trial. AB - BACKGROUND: Regular aerobic exercise in patients with cystic fibrosis (CF) improves aerobic conditioning and delays disease progression, resulting in better quality of life. The purpose of this study was to evaluate the effect of an aerobic exercise program based on verbal and written guidelines on maximum exercise capacity using a cardiopulmonary exercise test, quality of life, and the self-reported aerobic exercise practice of children and adolescents with CF. METHODS: This randomized controlled trial followed guidelines for physical exercise in a CF center. Subjects were assigned to 2 groups: intervention (group 1), with 17 subjects; and control (group 2), also with 17 subjects. Data were collected from October 2010 to October 2011, and the study population comprised 7 20-y-old children and adolescents with CF. The intervention consisted of handing out a manual with guidelines for aerobic physical exercises and reinforcing recommendations in telephone calls every 2 weeks. RESULTS: Thirty-four subjects were included in the study, 20 of whom were boys (58.5%). The groups were similar at baseline. In group 1, 6 subjects (35.2%) reported practicing physical exercises regularly. The mean age was 13.4 +/- 2.8 y, the mean percent-of predicted FEV1 was 95.5 +/- 17.9%, and the mean peak oxygen uptake (VO2 ) relative to body mass was 34.9 +/- 9.0 mL/kg/min. In group 2, 4 subjects (23.5%) reported practicing physical exercises regularly. The mean age was 12.7 +/- 3.3 y, the mean percent-of-predicted FEV1 was 100.1 +/- 21.2%, and the mean peak VO2 was 33.2 +/- 8.2 mL/kg/min. In group 1, there was a significant increase in physical exercise practice as reported by subjects after 3 months of intervention compared with group 2 (P = .01). No statistically significant differences were found for the other variables. CONCLUSIONS: Verbal and written guidelines for aerobic exercise, together with supervision over the telephone, had a positive impact on the self-reported regular physical exercise practice of children and adolescents. However, no improvement was found in lung function and maximum exercise capacity or domains of the quality of life questionnaire. PMID- 25140033 TI - Open-mouthpiece ventilation versus nasal mask ventilation in subjects with COPD exacerbation and mild to moderate acidosis: a randomized trial. AB - BACKGROUND: Open mouthpiece ventilation is efficacious in patients with neuromuscular disease. We used this ventilation technique in patients with exacerbations of COPD with mild to moderate acidosis. METHODS: The study was performed in 2 respiratory monitoring care units. Fifty subjects with exacerbations of COPD, breathing frequency > 25, PaCO2 > 45, and pH between 7.25 and 7.30, as well as Kelly scale <= 2 were enrolled. Subjects were randomly assigned to receive noninvasive ventilation (NIV) via nasal mask or mouthpiece ventilation. The primary outcome was improvement in arterial blood gases. Arterial blood gases and breathing frequency were recorded 2 h after the start of the enrollment and then after 12, 24, and 48 h. The duration of NIV, hospital stay, and acceptability of the interface (mouthpiece or nasal mask) using a Likert scale were assessed. RESULTS: No subjects had deterioration of gas exchange. The 2 groups had similar trends in arterial blood gases and breathing frequency. No differences in duration of NIV or hospital stay were noted. However, a significant difference in acceptability was found: subjects preferred mouthpiece ventilation (P < .01). CONCLUSIONS: Open mouthpiece ventilation is a useful technique and may prevent further deterioration of gas exchange in COPD patients with mild to moderate acidosis (similar to traditional NIV delivered by a nasal mask). www.chictr.org registration ChiCTR-TRC-12002672. PMID- 25140034 TI - Voluntary is better than involuntary cough peak flow for predicting re-intubation after scheduled extubation in cooperative subjects. AB - BACKGROUND: In this study, we compared the predictive accuracy of voluntary cough peak flow (V-CPF) and involuntary cough peak flow (IV-CPF) for re-intubation in mechanically ventilated subjects. METHODS: Endotracheally intubated patients who passed a spontaneous breathing trial and assessment of readiness for extubation were enrolled. Before extubation, V-CPF and IV-CPF were measured. Re-intubation was recorded at 72 h after extubation. RESULTS: A total of 115 extubations in 106 cooperative subjects (including 9 subjects with second extubation) and 5 extubations in 5 uncooperative subjects were recorded. At 72 h, 20 (17.4%) and 1 (25%) instances of re-intubation occurred in cooperative and uncooperative subjects, respectively. In cooperative subjects, those who had been successfully extubated had higher V-CPF than re-intubated subjects (81.3 +/- 41.4 vs 51.3 +/- 31.7, P = .003). However, rates were not significantly different with IV-CPF (70.9 +/- 39.8 vs 55.7 +/- 37.9, P = .121). Areas under the curve of the receiver operating characteristic in V-CPF and IV-CPF were 0.743 +/- 0.057 and 0.632 +/- 0.069 (P < .001 and P = .058, respectively, compared with area under the curve = 0.5). V-CPF had higher predictive accuracy for re-intubation than IV-CPF (P = .034). In subjects with a lower quartile and third quartile V-CPF (<= 43.2 L/min and 43.2-68.4 L/min, respectively), V-CPF was similar to IV-CPF. However, in second quartile and upper quartile V-CPF (68.4-99.0 L/min and > 99.0 L/min, respectively), V-CPF was higher than IV-CPF (82.1 +/- 9.6 vs 66.6 +/- 19.5 L/min, P < .001; 135.5 +/- 29.8 vs 116.2 +/- 38.2 L/min, P = .006, respectively). Overall, V-CPF was higher than IV-CPF (76.0 +/- 41.4 vs 68.2 +/- 39.7, P = .003). In uncooperative subjects, the IV-CPF was higher than V-CPF (40.2 +/- 10.2 vs 79.2 +/- 29.0, P = .042). CONCLUSIONS: V-CPF is noninvasive. It is much more accurate than IV-CPF as a predictor of re-intubation in cooperative patients because the IV-CPF may underestimate cough strength in patients with high V-CPF. However, it is unclear which is optimal for use in uncooperative patients. PMID- 25140035 TI - Identification of 9 serum microRNAs as potential noninvasive biomarkers of human astrocytoma. AB - BACKGROUND: Circulating microRNAs (miRNAs) are emerging as promising biomarkers for human cancer. In the current study, we investigated the potential use of serum miRNAs as biomarkers for diagnosis and prognosis in a cohort of Chinese astrocytoma patients. METHODS: An initial screening of the circulating miRNA expression profile was performed on pooled serum samples from 10 preoperative patients and 10 healthy controls using a TaqMan low-density array. The selected serum miRNAs were then validated in 90 preoperative patients and 110 healthy controls who were randomly divided into a training set and a validation set. An additional double-blind test was performed in 50 astrocytomas and 50 controls to assess the serum miRNA-based biomarker accuracy in predicting astrocytoma. The differentially expressed miRNAs were evaluated in paired preoperative and postoperative serum samples from 73 astrocytoma patients. The correlation of the miRNA levels with survival in astrocytoma samples was estimated. RESULTS: Nine serum miRNAs were significantly increased in the astrocytoma patients. The biomarker composed of these 9 miRNAs had high sensitivity, specificity, and accuracy. These 9 miRNAs were markedly decreased in the serum after operation. The upregulation of miR-20a-5p, miR-106a-5p, and miR-181b-5p was associated with advanced clinical stages of astrocytoma. Kaplan-Meier survival analysis showed that the high expression of miR-19a-3p, miR-106a-5p, and miR-181b-5p was significantly associated with poor patient survival. Finally, the combined 3 miRNAs panel was an important prognostic predictor, independent of other clinicopathological factors. CONCLUSIONS: The results indicated the potential of serum miRNAs as novel diagnostic and prognostic biomarkers for human astrocytoma. PMID- 25140036 TI - TERT promoter mutations: a novel independent prognostic factor in primary glioblastomas. AB - BACKGROUND: Activating somatic mutations in the promoter region of the telomerase reverse transcriptase gene (TERT) have been detected in several cancers. In this study we investigated the TERT promoter mutations and their impact on patient survival in World Health Organization grade IV glioblastoma multiforme (GBM). METHODS: The TERT core promoter region containing the previously described mutations and a common functional polymorphism (rs2853669) was sequenced in tumors and blood samples from 192 GBM patients. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was assessed by pyrosequencing in 177 (92.2%) cases. Relevant clinical data were obtained from a prospectively maintained electronic database. RESULTS: We detected specific (-124 C>T and -146 C>T) TERT promoter mutations in 143/178 (80.3%) primary GBM and 4/14 (28.6%) secondary GBM (P < .001). The presence of TERT mutations was associated with poor overall survival, and the effect was confined to the patients who did not carry the variant G-allele for the rs2853669 polymorphism. An exploratory analysis suggested that TERT mutations might be prognostic only in patients who had incomplete resections and no temozolomide chemotherapy. CONCLUSIONS: In this study, specific TERT promoter mutations were markers of primary GBM and predicted patient survival in conjunction with a common functional polymorphism. The prognostic impact of TERT mutations was absent in patients with complete resections and temozolomide chemotherapy. If confirmed in additional studies, these findings may have clinical implications, that is, TERT mutations appear to characterize tumors that require aggressive treatment. PMID- 25140037 TI - Efficacy of cabazitaxel in mouse models of pediatric brain tumors. AB - BACKGROUND: There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. METHODS: The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. RESULTS: This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. CONCLUSION: These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors. PMID- 25140040 TI - Time to diagnosis of axial spondylarthritis in clinical practice: signs of improving awareness? PMID- 25140038 TI - Periostin is a novel therapeutic target that predicts and regulates glioma malignancy. AB - BACKGROUND: Periostin is a secreted matricellular protein critical for epithelial mesenchymal transition and carcinoma metastasis. In glioblastoma, it is highly upregulated compared with normal brain, and existing reports indicate potential prognostic and functional importance in glioma. However, the clinical implications of periostin expression and function related to its therapeutic potential have not been fully explored. METHODS: Periostin expression levels and patterns were examined in human glioma cells and tissues by quantitative real time PCR and immunohistochemistry and correlated with glioma grade, type, recurrence, and survival. Functional assays determined the impact of altering periostin expression and function on cell invasion, migration, adhesion, and glioma stem cell activity and tumorigenicity. The prognostic and functional relevance of periostin and its associated genes were analyzed using the TCGA and REMBRANDT databases and paired recurrent glioma samples. RESULTS: Periostin expression levels correlated directly with tumor grade and recurrence, and inversely with survival, in all grades of adult human glioma. Stromal deposition of periostin was detected only in grade IV gliomas. Secreted periostin promoted glioma cell invasion and adhesion, and periostin knockdown markedly impaired survival of xenografted glioma stem cells. Interactions with alphavbeta3 and alphavbeta5 integrins promoted adhesion and migration, and periostin abrogated cytotoxicity of the alphavbeta3/beta5 specific inhibitor cilengitide. Periostin associated gene signatures, predominated by matrix and secreted proteins, corresponded to patient prognosis and functional motifs related to increased malignancy. CONCLUSION: Periostin is a robust marker of glioma malignancy and potential tumor recurrence. Abrogation of glioma stem cell tumorigenicity after periostin inhibition provides support for exploring the therapeutic impact of targeting periostin. PMID- 25140041 TI - Prevention of new osteitis on magnetic resonance imaging in patients with early axial spondyloarthritis during 3 years of continuous treatment with etanercept: data of the ESTHER trial. AB - OBJECTIVE: The aim of this study was to assess the degree of fluctuation of osteitis on MRI during long-term treatment with etanercept (ETN) in patients with early axial SpA (axSpA) with active inflammation (osteitis) on whole-body MRI in the spine and/or the SI joints at baseline. METHODS: We analysed MRI data from 328 SI joint quadrants and 943 spine vertebral units (VUs) in terms of osteitis in the pooled data set of 41 patients who were treated with ETN for 3 consecutive years. Scoring was performed by two blinded radiologists at baseline, year 2 and year 3. RESULTS: Through years 2 and 3, osteitis on MRI resolved completely in 56 of 144 (38.9%) SI joint quadrants and in 20 of 40 (50%) VUs affected at baseline, while persistent osteitis was found in 24 of 144 (16.7%) SI joint quadrants and in 8 of 40 (20.0%) spine VUs. The development of new osteitis in sites that were free of osteitis at baseline only occurred in 2 of 131 (1.5%) SI joint quadrants and in 3 of 862 (0.4%) spine VUs in both year 2 and year 3. CONCLUSION: There was a consistently small amount of osteitis on MRI in patients with early axSpA compared with baseline values, and only a very low rate of new-onset osteitis was found during 3 years of continuous treatment with ETN. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT00844142. PMID- 25140039 TI - Phase I/randomized phase II study of afatinib, an irreversible ErbB family blocker, with or without protracted temozolomide in adults with recurrent glioblastoma. AB - BACKGROUND: This phase I/II trial evaluated the maximum tolerated dose (MTD) and pharmacokinetics of afatinib plus temozolomide as well as the efficacy and safety of afatinib as monotherapy (A) or with temozolomide (AT) vs temozolomide monotherapy (T) in patients with recurrent glioblastoma (GBM). METHODS: Phase I followed a traditional 3 + 3 dose-escalation design to determine MTD. Treatment cohorts were: afatinib 20, 40, and 50 mg/day (plus temozolomide 75 mg/m(2)/day for 21 days per 28-day cycle). In phase II, participants were randomized (stratified by age and KPS) to receive A, T or AT; A was dosed at 40 mg/day and T at 75 mg/m(2) for 21 of 28 days. Primary endpoint was progression-free survival rate at 6 months (PFS-6). Participants were treated until intolerable adverse events (AEs) or disease progression. RESULTS: Recommended phase II dose was 40 mg/day (A) + T based on safety data from phase I (n = 32). Most frequent AEs in phase II (n = 119) were diarrhea (71% [A], 82% [AT]) and rash (71% [A] and 69% [AT]). Afatinib and temozolomide pharmacokinetics were unaffected by coadministration. Independently assessed PFS-6 rate was 3% (A), 10% (AT), and 23% (T). Median PFS was longer in afatinib-treated participants with epidermal growth factor receptor (EFGR) vIII-positive tumors versus EGFRvIII-negative tumors. Best overall response included partial response in 1 (A), 2 (AT), and 4 (T) participants and stable disease in 14 (A), 14 (AT), and 21 (T) participants. CONCLUSIONS: Afatinib has a manageable safety profile but limited single-agent activity in unselected recurrent GBM patients. PMID- 25140043 TI - Use of a water pipe is not an alternative to other tobacco or substance use among adolescents: results from a national survey in Sweden. AB - INTRODUCTION: Studies of social characteristics and substance use patterns among young users of water pipe are rare in Western countries, and no such study has been conducted in Sweden. METHODS: Cross-sectional study based on a national survey conducted in 2011, including 4,710 primary school students (15 years of age) and 3,624 high school students (17 years of age). Prevalence of lifetime and current water pipe use was compared among subgroups defined by other substance use, that is, cigarettes, snus, alcohol, and illicit drugs. Logistic regression was employed to calculate odds ratios (OR) of water pipe use and corresponding 95% confidence intervals (CI), conditionally on sociodemographic characteristics. RESULTS: Use of water pipe was associated with the use of other substances in both age groups. In particular, current use of water pipe at the age of 15 years was strongly associated with current cigarette smoking (OR = 6.46; CI = 5.13 8.14); use of snus (OR = 5.62; CI = 3.94-7.96); binge drinking (OR = 7.39; CI = 5.88-9.31); drunkenness (OR = 7.05; CI = 5.60-8.88); and recent use of illicit drugs (OR = 14.20; CI = 9.18-22.19). Annual alcohol consumption predicted water pipe use in a dose-response fashion. Cigarette smokers willing to quit used water pipe to a lower extent than smokers who did not intend to quit. Being an exclusive smoker of water pipe was associated with substance use when compared with a nonsmoker of tobacco, but not when compared with an exclusive smoker of cigarettes. CONCLUSIONS: Water pipe use among adolescents in Sweden is not a recreational tobacco use alternative to cigarettes and should be regarded as a marker of multiple substance use. PMID- 25140042 TI - Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events. AB - Imbalanced splicing of premessenger RNA is typical of tumorous malignancies, and the regulatory mechanisms involved in several tumorigenesis-associated splicing events are identified. Elevated expression of serine-arginine protein kinase 1 (SRPK1) may participate in the pathway responsible for the dysregulation of splicing events in malignant tumor cells. In this study, we observed a correlation between the cytoplasmic accumulation of RNA-binding motif protein 4 (RBM4) and up-regulated SRPK1 in breast cancer cells. The production of the IR-B and MCL-1S transcripts was induced separately by the overexpression of RBM4 and SRPK1 gene silencing. Overexpressed RBM4 simultaneously bound to the CU-rich elements within the MCL-1 exon2 and the downstream intron, which subsequently facilitated the exclusion of the regulated exon. Breast cancer cells are deprived of apoptotic resistance through the RBM4-mediated up-regulation of the IR-B and MCL-1S transcripts. These findings suggest that the splicing events regulated by the SRPK1-RMB4 network may contribute to tumorigenesis through altered sensitivity to apoptotic signals in breast cancer cells. PMID- 25140044 TI - Assessing the performance of two lung age equations on the Australian population: using data from the cross-sectional BOLD-Australia study. AB - INTRODUCTION: Lung age, a simple concept for patients to grasp, is frequently used as an aid in smoking cessation programs. Lung age equations should be continuously updated and should be made relevant for target populations. We observed how new lung age equations developed for Australian populations performed when utilizing the Burden of Obstructive Lung Disease (BOLD)-Australia dataset compared to more commonly used equations. METHODS: Data from a cross sectional population study of noninstitutionalized Australians aged >=40 years with analysis restricted to Caucasians <75 years. Lung age calculated using equations developed by Newbury et al. and Morris and Temple was compared with chronological age by smoking status and within smoking status. RESULTS: There were 2,793 participants with a mean age of 57 (+/-10 SD) years. More than half (52%) ever smoked, and 10.4% were current smokers. Prevalence of chronic obstructive pulmonary disease stage I or higher was 13.4% (95% confidence interval = 12.2, 14.7). For both genders, newer Newbury equations estimated lung ages significantly higher than actual age across all smoking groups (p < .05). Morris and Temple equations resulted in lung age estimates significantly lower than chronological age for nonsmokers (p < .05) but no difference among current smokers. Both equations showed exposure to smoking had lung ages higher than never-smokers (p < .001). Lung age also increased with increased pack-years. CONCLUSIONS: This supports the use of updated equations suited to the population of interest. The Australian Newbury equations performed well in the BOLD Australia dataset, providing more meaningful lung age profile compared to chronological age among smokers. Using equations not developed or ideally suited for our population is likely to produce misleading results. PMID- 25140045 TI - Smoking restrictions in homes after implementation of a smoking ban in public places. AB - INTRODUCTION: This Canadian study examines the prevalence of smoking restrictions in homes before and after the implementation of a public smoking ban, and their relation to tobacco use and cessation among a cohort of smokers. METHODS: Data were from a longitudinal cohort study of 1,058 smokers in the province of Quebec, Canada. Baseline data were collected through a population-based survey conducted 1 month before the implementation of the smoking ban with a representative sample of smokers. Follow-up data were collected 18 months after the ban with a response rate of 68%. Logistic regressions, paired t tests and chi-square statistics were used to examine the factors associated with smoking restrictions in homes, cigarette consumption, and quit attempts. RESULTS: Many smokers imposed partial or full smoking restrictions in their homes but proportions of smoke-free homes did not change significantly between baseline and follow-up. The presence of young children and nonsmokers significantly predicted full smoking restriction in the home. Knowledge about risks associated with exposure to secondhand smoke (SHS) and skepticism about the efficacy of methods to reduce exposure in the home also predicted maintenance of voluntary smoking restrictions in homes. The uptake of smoke-free homes was not associated with the quantity of cigarettes smoked or quit attempts. CONCLUSIONS: No significant change in home smoking bans was found 18 months after implementation of a public smoking ban. There remains a need for efforts to better inform smokers about health risks from exposure to SHS in homes and the reality that strategies other than a total smoking ban inside the home are ineffective. PMID- 25140046 TI - Neural coding of assessing another person's knowledge based on nonverbal cues. AB - For successful communication, conversational partners need to estimate each other's current knowledge state. Nonverbal facial and bodily cues can reveal relevant information about how confident a speaker is about what they are saying. Using functional magnetic resonance imaging, we aimed to identify brain regions that encode how confident a speaker is perceived to be. Participants viewed videos of people answering general knowledge questions and judged each respondent's confidence in their answer. Our results suggest a distinct role of two neural networks known to support social inferences, the so-called mentalizing and the mirroring network. While activation in both networks underlies the processing of nonverbal cues, only activity in the mentalizing network, most notably the medial prefrontal cortex and the bilateral temporoparietal junction, is modulated by how confident the respondent is judged to be. Our results support an integrative account of the mirroring and mentalizing network, in which the two systems support each other in aiding pragmatic processing. PMID- 25140047 TI - Oxytocin tempers calculated greed but not impulsive defense in predator-prey contests. AB - Human cooperation and competition is modulated by oxytocin, a hypothalamic neuropeptide that functions as both hormone and neurotransmitter. Oxytocin's functions can be captured in two explanatory yet largely contradictory frameworks: the fear-dampening (FD) hypothesis that oxytocin has anxiolytic effects and reduces fear-motivated action; and the social approach/avoidance (SAA) hypothesis that oxytocin increases cooperative approach and facilitates protection against aversive stimuli and threat. We tested derivations from both frameworks in a novel predator-prey contest game. Healthy males given oxytocin or placebo invested as predator to win their prey's endowment, or as prey to protect their endowment against predation. Neural activity was registered using 3T-MRI. In prey, (fear-motivated) investments were fast and conditioned on the amygdala. Inconsistent with FD, oxytocin did not modulate neural and behavioral responding in prey. In predators, (greed-motivated) investments were slower, and conditioned on the superior frontal gyrus (SFG). Consistent with SAA, oxytocin reduced predator investment, time to decide and activation in SFG. Thus, whereas oxytocin does not incapacitate the impulsive ability to protect and defend oneself, it lowers the greedy and more calculated appetite for coming out ahead. PMID- 25140048 TI - A meta-analysis of the anterior cingulate contribution to social pain. AB - Many functional magnetic resonance imaging studies have explored the neural correlates of social pain that results from social threat, exclusion, rejection, loss or negative evaluation. Although activations have consistently been reported within the anterior cingulate cortex (ACC), it remains unclear which ACC subdivision is particularly involved. To provide a quantitative estimation of the specific involvement of ACC subdivisions in social pain, we conducted a voxel based meta-analysis. The literature search identified 46 articles that included 940 subjects, the majority of which used the cyberball task. Significant likelihoods of activation were found in both the ventral and dorsal ACC for both social pain elicitation and self-reported distress during social pain. Self reported distress involved more specifically the subgenual and pregenual ACC than social pain-related contrasts. The cyberball task involved the anterior midcingulate cortex to a lesser extent than other experimental tasks. During social pain, children exhibited subgenual activations to a greater extent than adults. Finally, the ventro-dorsal gradient of ACC activations in cyberball studies was related to the length of exclusion phases. The present meta-analysis contributes to a better understanding of the role of ACC subdivisions in social pain, and it could be of particular importance for guiding future studies of social pain and its neural underpinnings. PMID- 25140049 TI - Social identity modifies face perception: an ERP study of social categorization. AB - Two studies examined whether social identity processes, i.e. group identification and social identity threat, amplify the degree to which people attend to social category information in early perception [assessed with event-related brain potentials (ERPs)]. Participants were presented with faces of Muslims and non Muslims in an evaluative priming task while ERPs were measured and implicit evaluative bias was assessed. Study 1 revealed that non-Muslims showed stronger differentiation between ingroup and outgroup faces in both early (N200) and later processing stages (implicit evaluations) when they identified more strongly with their ethnic group. Moreover, identification effects on implicit bias were mediated by intergroup differentiation in the N200. In Study 2, social identity threat (vs control) was manipulated among Muslims. Results revealed that high social identity threat resulted in stronger differentiation of Muslims from non Muslims in early (N200) and late (implicit evaluations) processing stages, with N200 effects again predicting implicit bias. Combined, these studies reveal how seemingly bottom-up early social categorization processes are affected by individual and contextual variables that affect the meaning of social identity. Implications of these results for the social identity perspective as well as social cognitive theories of person perception are discussed. PMID- 25140050 TI - The association between the 5-HTTLPR and neural correlates of fear conditioning and connectivity. AB - Strong evidence links the 5-HTTLPR genotype to the modulation of amygdala reactivity during fear conditioning, which is considered to convey the increased vulnerability for anxiety disorders in s-allele carriers. In addition to amygdala reactivity, the 5-HTTLPR has been shown to be related to alterations in structural and effective connectivity. The aim of this study was to investigate the effects of 5-HTTLPR genotype on amygdala reactivity and effective connectivity during fear conditioning, as well as structural connectivity [as measured by diffusion tensor imaging (DTI)]. To integrate different classification strategies, we used the bi-allelic (s-allele vs l/l-allele group) as well as the tri-allelic (low-functioning vs high-functioning) classification approach. S-allele carriers showed exaggerated amygdala reactivity and elevated amygdala-insula coupling during fear conditioning (CS + > CS-) compared with the l/l-allele group. In addition, DTI analysis showed increased fractional anisotropy values in s-allele carriers within the uncinate fasciculus. Using the tri-allelic classification approach, increased amygdala reactivity and amygdala insula coupling were observed in the low-functioning compared with the high functioning group. No significant differences between the two groups were found in structural connectivity. The present results add to the current debate on the influence of the 5-HTTLPR on brain functioning. These differences between s allele and l/l-allele carriers may contribute to altered vulnerability for psychiatric disorders. PMID- 25140052 TI - Outflanking RANK with a designer antagonist cytokine. AB - Members of the tumor necrosis factor (TNF) superfamily of cytokines are noncovalently linked trimers that play important roles in regulating the immune system and have emerged as successful therapeutic targets in various rheumatic and autoimmune conditions. Traditionally, antibodies to cytokines or receptor-Fc fusion proteins have been used to block signaling by TNF family cytokines. In this issue of Science Signaling, Warren et al. have taken a new approach to blocking the action of the TNF superfamily member RANKL [receptor activator of nuclear factor kappaB (RANK) ligand], which plays an important role in regulating bone turnover through stimulation of its receptor RANK on osteoclasts. Beginning with a single-chain fusion protein of three RANKL subunits, the authors used directed mutagenesis to generate a trimer consisting of a nonreceptor binding subunit fused to two "super-agonist" subunits that have increased affinity for RANK. This molecule antagonized the osteoclastogenic activity of wild-type RANKL in vitro and in vivo, thus providing insights into RANK signaling and a paradigm for the development of other antagonists of TNF family cytokines. PMID- 25140051 TI - Automatic emotion processing as a function of trait emotional awareness: an fMRI study. AB - It is unclear whether reflective awareness of emotions is related to extent and intensity of implicit affective reactions. This study is the first to investigate automatic brain reactivity to emotional stimuli as a function of trait emotional awareness. To assess emotional awareness the Levels of Emotional Awareness Scale (LEAS) was administered. During scanning, masked happy, angry, fearful and neutral facial expressions were presented to 46 healthy subjects, who had to rate the fit between artificial and emotional words. The rating procedure allowed assessment of shifts in implicit affectivity due to emotion faces. Trait emotional awareness was associated with increased activation in the primary somatosensory cortex, inferior parietal lobule, anterior cingulate gyrus, middle frontal and cerebellar areas, thalamus, putamen and amygdala in response to masked happy faces. LEAS correlated positively with shifts in implicit affect caused by masked happy faces. According to our findings, people with high emotional awareness show stronger affective reactivity and more activation in brain areas involved in emotion processing and simulation during the perception of masked happy facial expression than people with low emotional awareness. High emotional awareness appears to be characterized by an enhanced positive affective resonance to others at an automatic processing level. PMID- 25140053 TI - The ErbB4 CYT2 variant protects EGFR from ligand-induced degradation to enhance cancer cell motility. AB - The epidermal growth factor receptor (EGFR) is a member of the ErbB family that can promote the migration and proliferation of breast cancer cells. Therapies that target EGFR can promote the dimerization of EGFR with other ErbB receptors, which is associated with the development of drug resistance. Understanding how interactions among ErbB receptors alter EGFR biology could provide avenues for improving cancer therapy. We found that EGFR interacted directly with the CYT1 and CYT2 variants of ErbB4 and the membrane-anchored intracellular domain (mICD). The CYT2 variant, but not the CYT1 variant, protected EGFR from ligand-induced degradation by competing with EGFR for binding to a complex containing the E3 ubiquitin ligase c-Cbl and the adaptor Grb2. Cultured breast cancer cells overexpressing both EGFR and ErbB4 CYT2 mICD exhibited increased migration. With molecular modeling, we identified residues involved in stabilizing the EGFR dimer. Mutation of these residues in the dimer interface destabilized the complex in cells and abrogated growth factor-stimulated cell migration. An exon array analysis of 155 breast tumors revealed that the relative mRNA abundance of the ErbB4 CYT2 variant was increased in ER+ HER2- breast cancer patients, suggesting that our findings could be clinically relevant. We propose a mechanism whereby competition for binding to c-Cbl in an ErbB signaling heterodimer promotes migration in response to a growth factor gradient. PMID- 25140054 TI - Macromolecular assembly of the adaptor SLP-65 at intracellular vesicles in resting B cells. AB - The traditional view of how intracellular effector proteins are recruited to the B cell antigen receptor (BCR) complex at the plasma membrane is based on the occurrence of direct protein-protein interactions, as exemplified by the recruitment of the tyrosine kinase Syk (spleen tyrosine kinase) to phosphorylated motifs in BCR signaling subunits. By contrast, the subcellular targeting of the cytosolic adaptor protein SLP-65 (Src homology 2 domain-containing leukocyte adaptor protein of 65 kD), which serves as a proximal Syk substrate, is unclear. We showed that SLP-65 activation required its association at vesicular compartments in resting B cells. A module of ~50 amino acid residues located at the amino terminus of SLP-65 anchored SLP-65 to the vesicles. Nuclear magnetic resonance spectroscopy showed that the SLP-65 amino terminus was structurally disordered in solution but could bind in a structured manner to noncharged lipid components of cellular membranes. Our finding that preformed vesicular signaling scaffolds are required for B cell activation indicates that vesicles may deliver preassembled signaling cargo to sites of BCR activation. PMID- 25140055 TI - Manipulation of receptor oligomerization as a strategy to inhibit signaling by TNF superfamily members. AB - Signaling by receptor activator of nuclear factor kappaB (RANK) in response to its ligand RANKL, which is a member of the tumor necrosis factor (TNF) superfamily of cytokines, stimulates osteoclast formation and bone resorption. Thus, this ligand-receptor pair is a therapeutic target for various disorders, such as osteoporosis and metastasis of cancer to bone. RANKL exists as a physiological homotrimer, with each monomer recognizing a single molecule of RANK or the decoy receptor osteoprotegerin (OPG), which inhibits osteoclastogenesis. We engineered a RANKL protein in which all three monomers of RANKL were encoded as a single polypeptide chain, which enabled us to independently control receptor binding at each binding interface. To generate an effective RANK inhibitor, we used an unbiased forward genetic approach to identify mutations in RANKL that had a 500-fold increased affinity for RANK but had decreased affinity for the decoy receptor OPG. Incorporating mutations that blocked receptor binding into this high-affinity RANKL variant generated a mutant RANKL that completely inhibited wild-type RANKL-induced osteoclastogenesis in vitro and bone resorption in mice. Our approach may be generalized to enable the inhibition of other TNF receptor signaling systems, which are implicated in a wide range of pathological conditions. PMID- 25140056 TI - The incidence of secondary vertebral fracture of vertebral augmentation techniques versus conservative treatment for painful osteoporotic vertebral fractures: a systematic review and meta-analysis. AB - BACKGROUND: Percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP) are minimally invasive and effective vertebral augmentation techniques for managing osteoporotic vertebral compression fractures (OVCFs). Recent meta-analyses have compared the incidence of secondary vertebral fractures between patients treated with vertebral augmentation techniques or conservative treatment; however, the inclusions were not thorough and rigorous enough, and the effects of each technique on the incidence of secondary vertebral fractures remain unclear. PURPOSE: To perform an updated systematic review and meta-analysis of the studies with more rigorous inclusion criteria on the effects of vertebral augmentation techniques and conservative treatment for OVCF on the incidence of secondary vertebral fractures. MATERIAL AND METHODS: PubMed, MEDLINE, EMBASE, SpringerLink, Web of Science, and the Cochrane Library database were searched for relevant original articles comparing the incidence of secondary vertebral fractures between vertebral augmentation techniques and conservative treatment for patients with OVCFs. Randomized controlled trials (RCTs) and prospective non-randomized controlled trials (NRCTs) were identified. The methodological qualities of the studies were evaluated, relevant data were extracted and recorded, and an appropriate meta-analysis was conducted. RESULTS: A total of 13 articles were included. The pooled results from included studies showed no statistically significant differences in the incidence of secondary vertebral fractures between patients treated with vertebral augmentation techniques and conservative treatment. Subgroup analysis comparing different study designs, durations of symptoms, follow-up times, races of patients, and techniques were conducted, and no significant differences in the incidence of secondary fractures were identified (P > 0.05). No obvious publication bias was detected by either Begg's test (P = 0.360 > 0.05) or Egger's test (P = 0.373 > 0.05). CONCLUSION: Despite current thinking in the field that vertebral augmentation procedures may increase the incidence of secondary fractures, we found no differences in the incidence of secondary fractures between vertebral augmentation techniques and conservative treatment for patients with OVCFs. PMID- 25140057 TI - CT chest and gantry rotation time: does the rotation time influence image quality? AB - BACKGROUND: Computed tomography (CT) gantry rotation time is one factor influencing image quality. Until now, there has been no report investigating the influence of gantry rotation time on chest CT image quality. PURPOSE: To investigate the influence of faster gantry rotation time on image quality and subjective and objective image parameters in chest CT imaging. MATERIAL AND METHODS: Chest CT scans from 160 patients were examined in this study. All scans were performed using a single-source mode (collimation, 128 * 0.6 mm; pitch, 1.2) on a dual-source CT scanner. Only gantry rotation time was modified, while other CT parameters were kept stable for each scan (120 kV/110 reference mAs). Patients were divided into four groups based on rotation time: group 1, 1 s/ rotation (rot); group 2, 0.5 s/rot; group 3, 0.33 s/rot; group 4, 0.28 s/rot. Two blinded radiologists subjectively compared CT image quality, noise, and artifacts, as well as radiation exposure, from all groups. For objective comparison, all image datasets were analyzed by a radiologist with 5 years of experience concerning objective measurements as well as signal-to-noise ratio (SNR). RESULTS: We found that faster gantry rotation times (0.28 s/rot and 0.33 s/rot) resulted in more streak artifacts, image noise, and decreased image quality. However, there was no significant difference in radiation exposure between faster and slower rotation times (P > 0.7). CONCLUSION: Faster CT gantry rotation reduces scan time and motion artifacts. However, accelerating rotation time increases image noise and streak artifacts. Therefore, a slower CT gantry rotation speed is still recommended for higher image quality in some cases. PMID- 25140058 TI - Dilatation of the Virchow-Robin spaces as an indicator of unilateral carotid artery stenosis: correlation with white matter lesions. AB - BACKGROUND: Virchow-Robin space (VRS) dilatation is related to many pathologic conditions, mostly associated with vascular abnormalities. White matter lesions (WMLs) are commonly seen on brain magnetic resonance imaging (MRI) with advancing age and generally considered as potential markers for vascular disease. PURPOSE: To investigate if asymmetric dilatation of VRSs and WMLs are associated with unilateral internal carotid artery stenosis (ICAS) and to test the relationship between dilated VRSs and common vascular risk factors. MATERIAL AND METHODS: Twenty-nine patients (18 men, 11 women; mean age, 68.62 years) with unilateral ICAS (>=70% carotid stenosis) undergoing carotid endarterectomy were identified for this Health Insurance Portability and Accountability Act (HIPAA) compliant prospective study and assessed with brain MRI. Two experienced radiologists scored VRSs and WMLs and evaluated old infarcts, chronic lacunar infarcts, and cerebral atrophy. Asymmetry of WML and VRS scores between two cerebral hemispheres was assessed and associations between VRS scores, WML scores, and explanatory variables (e.g. age, sex, vascular risk factors, and atrophy) were tested. RESULTS: In this study, WMLs and basal ganglia VRSs were significantly greater in the unilateral hemisphere with ICA stenosis than contralateral hemisphere. Basal ganglia VRSs were associated with WMLs and internal cerebral atrophy. No association between the severity of VRSs and vascular risk factors was found. CONCLUSION: ICA stenosis may contribute as a factor in the development of WMLs and dilatation of VRSs by causing chronic hypoperfusion. VRS dilatation may be an additional MRI marker of ICAS. PMID- 25140059 TI - The 25-year genetic era in hypertrophic cardiomyopathy: revisited. PMID- 25140060 TI - Is the phenotype-genotype relationship necessary to understand cardiomyopathies? PMID- 25140061 TI - Network biology in medicine and beyond. PMID- 25140062 TI - TraceRNA: a web application for competing endogenous RNA exploration. PMID- 25140064 TI - Cardiac cell therapy in nonhuman primates: a significant step toward clinical translation. PMID- 25140063 TI - A clinical approach to inherited premature coronary artery disease. PMID- 25140065 TI - MicroRNA passenger strand: orchestral symphony of paracrine signaling. PMID- 25140066 TI - Prognostic implications of the systolic to diastolic duration ratio in children with idiopathic or familial dilated cardiomyopathy. AB - BACKGROUND: Childhood dilated cardiomyopathy (DCM) carries high morbidity and mortality. The echocardiographic systolic to diastolic (S:D) duration ratio, an indicator of global cardiac performance, is elevated in DCM; however, its prognostic implications have not been investigated in this population. METHODS AND RESULTS: We investigated systolic and diastolic durations and the resultant S:D ratio using pulsed tissue Doppler imaging in children with idiopathic or familial DCM. We studied serial echocardiograms from presentation until the last follow-up echo. Results were compared with heart rate-matched controls and between DCM subgroups based on an acute or insidious presentation. The association between S:D ratio and death or need for transplant was analyzed. All analyses were adjusted for repeated measures per patient. We studied 200 serial echocardiograms of 48 children with DCM (7.0+/-6.0 years) and 25 controls. Adjusted for repeated measures through a compound symmetry covariance structure, the S:D ratio was higher in DCM patients (-0.425 [0.072]; P<0.001) because of shortened diastole. A S:D ratio >1.2 at presentation and on serial evaluation was associated with a hazard ratio of 10.5 (95% confidence interval, 3.9-27.8; P<0.001) for death or transplant. In combined multivariable analysis, a S:D ratio >1.2 remained significantly associated with hazard of death/transplant (hazard ratio, 9.1; P=0.04) after adjustment for ejection fraction (hazard ratio: 2.2 per -10%; P<0.001). CONCLUSIONS: A high S:D ratio is associated with increased risk for death or need for transplant in children with DCM across the spectrum of heart rates and may be a useful prognostic index for serial evaluation of children with DCM. PMID- 25140067 TI - Quantification of left ventricular interstitial fibrosis in asymptomatic chronic primary degenerative mitral regurgitation. AB - BACKGROUND: The optimum timing of surgery in asymptomatic patients with chronic severe primary degenerative mitral regurgitation (MR) remains controversial, and further markers are needed to improve decision-making. There are limited data that wall stress is increased in MR and may result in ventricular fibrosis. We investigated the hypothesis that chronic volume overload in MR is a stimulus for myocardial fibrosis using T1-mapping cardiac MRI. METHODS AND RESULTS: A cross sectional study of 35 patients (age 60 +/- 14 years) with asymptomatic moderate and severe primary degenerative MR (mean effective regurgitant orifice area, 0.45 +/- 0.25 cm)(2) with no class I indication for surgery were compared with age and sex controls. Subjects were studied with cardiopulmonary exercise testing, echocardiography, and cardiac MRI. Longitudinal and circumferential myocardial deformation was reduced with MR when left ventricular ejection fraction (67% +/- 10%) and N-terminal pro B Natriuretic peptide (126 [76-428] ng/L) were within the normal range. Myocardial extracellular volume was increased (0.32 +/- 0.07 versus 0.25 +/- 0.02, P<0.01) and was associated with increased left ventricular end systolic volume index (r=0.62, P<0.01), left atrial volume index (r=0.41, P<0.05) but lower left ventricular ejection fraction (r=-0.60, P<0.01), longitudinal function (mitral annular plane systolic excursion, r=-0.46, P<0.01), and peak VO2 max (r=-0.51, P<0.05). In a multivariable regression model, left ventricular end systolic volume index and left atrial volume index were independent predictors of extracellular volume (r(2)=0.42, P<0.01). CONCLUSIONS: Patients with asymptomatic MR demonstrate a spectrum of myocardial fibrosis associated with reduced myocardial deformation and reduced exercise capacity. Future work is warranted to investigate whether left ventricle fibrosis affects clinical outcomes. PMID- 25140068 TI - Interpolating U.S. Decennial Census Tract Data from as Early as 1970 to 2010: A Longtitudinal Tract Database. AB - Differences in the reporting units of data from diverse sources and changes in units over time are common obstacles to analysis of areal data. We compare common approaches to this problem in the context of changes over time in the boundaries of U.S. census tracts. In every decennial census many tracts are split, consolidated, or changed in other ways from the previous boundaries to reflect population growth or decline. We examine two interpolation methods to create a bridge between years, one that relies only on areal weighting and another that also introduces population weights. Results demonstrate that these approaches produce substantially different estimates for variables that involve population counts, but they have a high degree of convergence for variables defined as rates or averages. Finally the paper describes the Longitudinal Tract Data Base (LTDB), through which we are making available public-use tools to implement these methods to create estimates within 2010 tract boundaries for any tract-level data (from the census or other sources) that are available for prior years as early as 1970. PMID- 25140069 TI - Relative ion yields in mammalian cell components using C60 SIMS. AB - Time of flight secondary ion mass spectrometry has been used to better understand the influence of molecular environment on the relative ion yields of membrane lipid molecules found in high abundance in a model mammalian cell line, RAW264.7. Control lipid mixtures were prepared to simulate lipid-lipid interactions in the inner and outer leaflet of cell membranes. Compared with its pure film, the molecular ion yields of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl 2-oleoyl-sn-glycero-3-phosphocholine are suppressed when mixed with 2-dipalmitoyl sn-glycero-3-phosphocholine. In the mixture, proton competition between 1,2 dioleoyl-sn-glycero-3-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine, and 2-dipalmitoyl-sn-glycero-3-phosphocholine led to lower ionization efficiency. The possible mechanism for ion suppression was also investigated with 1H and 13C nuclear magnetic resonance spectroscopy. The formation of a hydroxyl bond in lipid mixtures confirms the mechanism involving proton exchange with the surrounding environment. Similar effects were observed for lipid mixtures mimicking the composition of the inner leaflet of cell membranes. The secondary molecular ion yield of 1-palmitoyl-2-oleoyl-sn-glycero-3 phospho-L-serine was observed to be enhanced in the presence of 1-palmitoyl-2 oleoyl-sn-glycero-3-phosphoethanolamine. PMID- 25140071 TI - Multi-directional local search. AB - This paper introduces multi-directional local search, a metaheuristic for multi objective optimization. We first motivate the method and present an algorithmic framework for it. We then apply it to several known multi-objective problems such as the multi-objective multi-dimensional knapsack problem, the bi-objective set packing problem and the bi-objective orienteering problem. Experimental results show that our method systematically provides solution sets of comparable quality with state-of-the-art methods applied to benchmark instances of these problems, within reasonable CPU effort. We conclude that the proposed algorithmic framework is a viable option when solving multi-objective optimization problems. PMID- 25140070 TI - Serum interleukin 17 levels in patients with Crohn's disease: real life data. AB - The aim of this study was to investigate serum IL17 levels in patients with Crohn's disease (CD) and to investigate the relationship between serum IL17 levels with disease activity. METHODS: Fifty patients with CD and sex- and age matched 40 healthy controls were included in the study. The serum IL17 levels, complete blood count, blood chemistry, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were measured, and Crohn's disease activity was calculated using Crohn's disease activity index (CDAI). RESULTS: The mean serum IL17 level of CD patients did not differ from those of healthy controls (P > 0.05). There was no difference between the mean serum IL levels of active CD patients and of quiescent CD patients (P > 0.05). However, the mean IL17 level of active patients was lower than of control subjects (P = 0.02). Serum IL17 was not correlated with inflammatory markers (ESR, CRP, white blood count, platelet count, and albumin) and CDAI. CONCLUSIONS: Peripheral blood serum IL17 levels of CD patients were not higher than of healthy controls, and also, serum IL17 level was not correlated with clinical disease activity. Peripheral IL17 measurement is not a useful tool for detecting and monitoring Crohn's disease which is understood to have complex etiopathogenesis. PMID- 25140072 TI - Informed Consent and Ethical Review in Chinese Human Experimentation: Reflections on the "Golden Rice Event" PMID- 25140073 TI - Evaluation of the method of hemostasis after femoral arterial puncture. AB - [Purpose] This study assessed the advantages and shortcomings of methods for hemostasis in patients who had received angiography after femoral arterial puncture using manual, compression device, or a combination of manual compression and a compression device. In addition, the success rates, complications, etc, were analyzed. [Subjects and Methods] One hundred and eighty patients who had undergone angiography after femoral arterial puncture were divided into three groups according to the method of hemostasis. For group A, immediately after angiography, an Angio-Seal device was placed in the puncture area and compressed using a compression device. For group B, after angiography, the puncture area was compressed with the hands directly. For group C, the puncture area was compressed using a compression device for approximately 10 min, and the puncture area was then compressed with the hands. In each group, the following correlations were analyzed: the time to hemostasis after angiography and gender, the time to hemostasis of each generation and the hemoglobin value, and platelet value and the time to hemostasis. [Results] The results showed a similar time to hemostasis regardless of gender or generation. The correlation between the hemoglobin value, platelet value, and the time to hemostasis were not significant. Group A showed the shortest mean time to hemostasis of the three groups (20.37 +/- 8.23 min). No complications caused by the hemostasis method were detected in group B. Group A showed the highest incidence of complications caused by hemostasis. [Conclusion] Overall, hemostasis performed mutually is safe and effective for patients according to their condition. PMID- 25140074 TI - Correlation between Intrinsic Patellofemoral Pain Syndrome in Young Adults and Lower Extremity Biomechanics. AB - [Purpose] The purpose of this study was to evaluate the correlation between intrinsic patellofemoral pain syndrome (PFPS) in young adults and lower extremity biomechanics. [Subjects] This experiment was carried out with sixty (24 men and 32 women), who are normal university students as subjects. [Methods] All subjects underwent 3 clinical evaluations. For distinguishing the intrinsic PFPS from controls, we used the Modified Functional Index Questionnaire (MFIQ), Clarke's test and the Eccentric step test. Based on the results of the tests, subjects who were classified as positive for 2 more tests were allocated to the bilateral or unilateral intrinsic PFPS group (n=14), and the others were allocated to the control group (n=42). These two groups were tested for hamstring tightness, foot overpronation, and static Q-angle and dynamic Q-angle. These are the four lower extremity biomechanic, cited as risk factors of patellofemoral pain syndrome. [Results] The over pronation, static Q-angle and the dynamic Q-angle were not significantly different between the two groups. However, the hamstring tightness of the PFPS group was significantly greater than that of the controls. [Conclusion] We examined individuals for intrinsic patellofemoral pain syndrome in young adults and lower extremity biomechanics. We found a strong correlation between intrinsic PFPS and hamstring tightness. PMID- 25140075 TI - The effect of ground tilt on the lower extremity muscle activity of stroke patients performing squat exercises. AB - [Purpose] The purpose of this study was to determine the effect of ground tilt on the lower extremity muscle activity of stroke patients performing squat exercises. [Subjects] Fifteen hemiparetic patients volunteered to participate in this study. [Methods] The subjects performed squat exercises at three different ground tilt angles: 15 degrees plantar flexion, a neutral position, and 15 degrees dorsiflexion. A surface electromyogram (sEMG) was used to record the electromyographic activities of the leg extensor muscle in the vastus lateralis (VL), vastus medialis (VM), gastrocnemius lateralis (GL), and gastrocnemius medialis (GM). The sEMG activity was analyzed using a one-way repeated measures ANOVA and a post hoc Bonferroni correction. [Results] The results of this study are summarized as follows. Significant differences were noted for the VL and the GL when the angle of the ankle joint was between the 15 degrees plantar flexion and neutral positions during squat exercises involving the VL and when the angle of the ankle joint was between the neutral position and 15 degrees dorsiflexion during squat exercises involving the VM. [Conclusion] In this study, sEMG showed that the VL and GL changed significantly during squat exercises according to the ground tilt angle of hemiparetic patients. Therefore, squat exercises with different ground tilt angles can be used to improve VL and GL strength. PMID- 25140076 TI - Effect of the Frequency and Duration of Land-based Therapeutic Exercise on Pain Relief for People with Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. AB - [Purpose] This study aimed to investigate the influence of land-based exercise frequency and duration on pain relief for people with knee osteoarthritis (OA). [Subjects and Methods] The systematic review included randomized controlled trials that investigated this influence, which were identified by searches of PubMed, the Cochrane Central Register of Controlled Trials, the Physiotherapy Evidence Database, and the Cumulative Index to Nursing and Allied Health Literature. The exercise groups in the identified trials were categorized according to their type, frequency, and duration of exercise, and subgroup analyses were performed. [Results] Data integration of 17 studies (23 exercise groups) revealed a significant effect and a medium effect size. In subgroups involving strengthening exercise programs of >=9 weeks duration, heterogeneity was found between subjects who performed up to 3 sessions/week and those who performed >=4 sessions/week. In subgroups involving strengthening exercise programs of up to 3 sessions/week, there was heterogeneity between subjects who exercised for up to 8 weeks and those who exercised for >=9 weeks. Heterogeneity was not confirmed in aerobic exercise subgroups. [Conclusion] Differences in exercise frequency and duration influence pain relief in effects of strengthening exercises but do not influence the effect size of aerobic exercise for people with knee OA. PMID- 25140077 TI - Effect of gross motor group exercise on functional status in chronic stroke: a randomized controlled trial. AB - [Purpose] The aim of this study was to understand the effects of task-oriented gross motor group exercise based on motor development on chronic stroke patients' joint, bone, muscle, and motor functions and activities of daily living. [Subjects] Twenty-eight stroke patients hospitalized at P municipal nursing facility for the severely handicapped were randomly assigned to the gross motor group exercise group (experimental group, n=14) or the control group (n=14). [Methods] The two groups performed morning exercise led by a trainer for 30 minutes a day, 5 times a week for 6 weeks in total. The experimental group performed a gross motor group exercise in addition to this exercise for 50 minutes a day, 3 times a week for 6 weeks in total. Before the experiment, all subjects were measured with the Modified Barthel Index (MBI) and for their neuromuscular skeletal and motor-related functions according to the International Classification of Functioning, Disability and Health. [Results] Significant improvements were found in the experimental group's neuromusculoskeletal and motor-related functions and MBI test, except for the stability of joint functions. The control group showed no significant difference from the initial evaluation. [Conclusion] The gross motor group exercise based on motor development is recommended for chronic stroke patients with severe handicaps. PMID- 25140078 TI - Effects of the nerve mobilization technique on lower limb function in patients with poststroke hemiparesis. AB - [Purpose] The purpose of the study was to determine the effects of a sciatic nerve mobilization technique on improvement of lower limb function in patient with poststroke hemiparesis. [Subjects] Twenty- two stroke patients participated in this study. [Methods] They were randomly selected based on selection criteria and divided into two groups. In the subject group (n=10), sciatic nerve mobilization with conventional physical therapy was applied to patients. In the control group (n=10), only conventional physical therapy was applied to stroke patients. [Results] There were significant differences between the two groups in pressure, sway, total pressure, angle of the knee joint, and functional reaching test results in the intervention at two weeks and at four weeks. [Conclusion] The present study showed that sciatic nerve mobilization with conventional physical therapy was more effective for lower limb function than conventional physical therapy alone in patient with poststroke hemiparesis. PMID- 25140079 TI - A Pilot Study on Pain and the Upregulation of Myoglobin through Low-frequency and High-amplitude Electrical Stimulation-induced Muscle Contraction. AB - [Purpose] It is well known that, in both in vivo and in vitro tests, muscle fatigue is produced by severe exercise, electrical stimulation, and so on. However, it is not clear whether or not low-frequency and high-amplitude modulation specifically affects serum myoglobin or urine myoglobin. The purpose of the present study was to determine the effect of low-frequency and high amplitude modulation on serum myoglobin and urine myoglobin. [Methods] The study used whole blood samples and urine produced over 24 hours from the thirteen healthy subjects. [Results] There was a significant increase in serum myoglobin following electrical stimulation at a frequency of 10 Hz compared with the control group. Furthermore, within 24 hours, urine myoglobin also showed a significant increase for the test volunteers subjected to electrical stimulation at the 10 Hz frequency compared with the control group. However, there were no significant differences in the concentrations of hematologic results in subjects treated with electrical stimulation. [Conclusion] These results suggest that increased myoglobin related to muscle fatigue from electrical stimulation, particularly with a current of 10 Hz combined with a high-amplitude, may be partially related to increased muscle damage. PMID- 25140080 TI - Effect of Weight-bearing Therapeutic Exercise on the Q-angle and Muscle Activity Onset Times of Elite Athletes with Patellofemoral Pain Syndrome: A Randomized Controlled Trial. AB - [Purpose] The purpose of this study was to determine the effect of a weight bearing therapeutic exercise program for elite athletes diagnosed as having patellofemoral pain syndrome (PFPS). [Subjects] The subjects were 34 elite athletes from the Seoul T Center. They were randomly allocated to three groups: an elastic band exercise group (EBG), a sling exercise group (SEG), or a control group (CG). [Methods] Therapeutic exercises were performed 3 times a week for 8 weeks. The visual analogue scale (VAS) hamstring length, and static and dynamic Q angles were used to test the exercise effect of the exercises, as well as the onset time of electromyographic activity of vastus medialis oblique (VMO) and vastus lateralis (VL). [Results] Decrease of the dynamic Q-angle in EBG was significant and significantly greater than that in CG. The decrease in VAS in SEG was significant and significantly greater than that in CG. There were significant differences in the VL and VMO activity onset times in SEG between pre- and post test, and their differences between pre- and post-test were also significantly different. [Conclusion] Weight-bearing therapeutic exercise is hoped that clinicians will use this information for better implementation of effective exercise methods for elite athletes with PFPS. PMID- 25140081 TI - Reliability of pinch strength testing in elderly subjects with unilateral thumb carpometacarpal osteoarthritis. AB - [Purpose] The aim of this study was to examine the test-retest reliability of pinch strength testing in elderly subjects with thumb CMC OA. [Subjects and Methods] A total of 27 patients with unilateral right-thumb CMC OA (mean +/- SD age: 81.3 +/- 4.7 years) were recruited. Each patient performed three pain-free maximal isometric contractions on each hand on two occasions, one week apart. Three different measurements were taken: tip, tripod, and key pinch strength. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), and 95% limits of agreement (LOA) calculations were performed. [Results] Test retest reliability of measurements of tip, tripod, and key pinch strength was excellent for the affected side (ICC=0.93, 0.96, and 0.99) and the contralateral thumb (ICC=0.91, 0.92, and 0.94). [Conclusions] The present results indicate that maximum pinch strength can be measured reliably using the Pinch Gauge Dynamometer, in patients with thumb CMC OA, which enables its use in research and in the clinic to determine the effect of interventions on improving pinch strength. PMID- 25140082 TI - Accelerometer and gyroscope based gait analysis using spectral analysis of patients with osteoarthritis of the knee. AB - [Purpose] A wide variety of accelerometer tools are used to estimate human movement, but there are no adequate data relating to gait symmetry parameters in the context of knee osteoarthritis. This study's purpose was to evaluate a 3D kinematic system using body-mounted sensors (gyroscopes and accelerometers) on the trunk and limbs. This is the first study to use spectral analysis for data post processing. [Subjects] Twelve patients with unilateral knee osteoarthritis (OA) (10 male) and seven age-matched controls (6 male) were studied. [Methods] Measurements with 3-D accelerometers and gyroscopes were compared to video analysis with marker positions tracked by a six-camera optoelectronic system (VICON 460, Oxford Metrics). Data were recorded using the 3D-kinematic system. [Results] The results of both gait analysis systems were significantly correlated. Five parameters were significantly different between the knee OA and control groups. To overcome time spent in expensive post-processing routines, spectral analysis was performed for fast differentiation between normal gait and pathological gait signals using the 3D-kinematic system. [Conclusions] The 3D kinematic system is objective, inexpensive, accurate and portable, and allows long-term recordings in clinical, sport as well as ergonomic or functional capacity evaluation (FCE) settings. For fast post-processing, spectral analysis of the recorded data is recommended. PMID- 25140083 TI - Immediate Effect of Postural Insoles on Gait Performance of Children with Cerebral Palsy: Preliminary Randomized Controlled Double-blind Clinical Trial. AB - [Purpose] Improved gait efficiency is one of the goals of therapy for children with cerebral palsy (CP). Postural insoles can allow more efficient gait by improving biomechanical alignment. The aim of the present study was to assess the effect of postural insoles on gait performance of children with CP classified as levels I or II of the Gross Motor Function Classification System (GMFCS). [Subjects and Methods] the study was a randomized controlled double-blind clinical trial. After meeting the legal aspects and the eligibility criteria, 10 children between four and 12 years old were randomly divided into a two groups: a control group (n=5), and an experimental group (n=5). Children in the control group used a placebo insoles, and children in the experimental group used postural insoles. Evaluation consisted of three-dimensional gait analysis under three conditions: barefoot, shoes without insoles and shoes with postural insoles or shoes with placebo insoles. [Results] Regarding the immediate effects of insole use, significant improvements in gait velocity and cadence were observed in the experimental group in comparison to the control group. [Conclusion] The use of postural insoles led to improvements in gait velocity and cadence of the children with cerebral palsy classified as levels I or II of the GMFCS. PMID- 25140085 TI - Effect of smart phone use on dynamic postural balance. AB - [Purpose] The present study investigated what kind of effect smart phone use has on dynamic postural balance. [Subjects] The study subjects were 30 healthy students in their 20's who were recruited from a University in Busan, Korea. [Methods] The present experiment was quasi-experimental research which measured the postural balance (Biodex) of subjects while they sent text messages via smart phones in the standing position with the eyes open, and while they used two-way SNS. [Results] There were significant differences between standing and the dual task situations. Among dual tasks using smart phones, SNS using situations showed the highest instability. [Conclusion] The use of smart phones in less stable conditions such as while walking or in moving vehicles should be discouraged. PMID- 25140084 TI - Comparison of upper extremity motor recovery of stroke patients with actual physical activity in their daily lives measured with accelerometers. AB - [Purpose] This study compared the upper extremity recovery of stroke patients with the amount of their upper extremity use in real life as measured by accelerometers. [Subjects] Forty inpatients who had had a stroke were recruited. [Methods] The subjects were divided into two groups by the Fugl-Meyer Assessment of Motor Function (FMA) score, a moderately recovered group and a well recovered group. The amount of upper extremity physical activity and its ratio in daily time periods were analyzed for the affected and unaffected sides. [Results] The well recovered group showed significantly higher affected arm use and use ratio than the moderately recovered group in all time periods. [Conclusion] The upper extremity recovery level of the affected side is similar to the physical activity level according to the amount of upper extremity physical activity in actual life measured with an accelerometer. Overuse of the normal side regardless of the recovery level of upper extremity proves the International Classification of Functioning (ICF) concept of differentiating between capacity and performance, and rehabilitation treatments should focus on improving performance. PMID- 25140086 TI - Effects of neuromobilization maneuver on clinical and electrophysiological measures of patients with carpal tunnel syndrome. AB - [Purpose] The aim of this study was to investigate the efficacy of neuromobilization combined with routine physiotherapy in patients with carpal tunnel syndrome through subjective, physical, and electrophysiological studies. [Subjects and Methods] Twenty patients with carpal tunnel syndrome (totally 32 hands) were assigned two groups: treatment and control groups. In both groups, patients received the routine physiotherapy. In addition to the routine physiotherapy, patients in the treatment group received neuromobilization. The symptoms severity scale, visual analogue scale, functional status scale, Phalen's sign, median nerve tension test, and median nerve distal sensory and motor latency were assessed. [Results] There were significant improvements in the symptoms severity scale, visual analogue scale, median nerve tension test, and Phalen's sign in both groups. However, the functional status scale and median nerve distal motor latency were significantly improved only in the treatment group. [Conclusion] Neuromobilization in combination with routine physiotherapy improves some clinical findings more effectively than routine physiotherapy. Therefore, this combination can be used as an alternative effective non-invasive treatment for patients with carpal tunnel syndrome. PMID- 25140087 TI - Effects of Pelvic Belt on Hip Extensor Muscle EMG Activity during Prone Hip Extension in Females with Chronic Low Back Pain. AB - [Purpose] This study assessed the effects of a pelvic belt (PB) on the electromyography (EMG) activity of the elector spinae (ES), gluteus maximus (GM), and biceps femoris (BF) in females with chronic low back pain (CLBP) during prone hip extension (PHE). [Subjects] Twenty female with CLBP were recruited. Surface EMG data were collected from the ES, GM, and BF muscles during a PHE task. [Results] The EMG activity in the ES bilaterally, and the right GM decreased significantly when a PB was applied compared with when a PB was not applied. [Conclusion] This suggests that a PB is effective for altering the activation pattern of the hip extensor muscles in females with CLBP during PHE. PMID- 25140088 TI - Tai Chi Exercise can Improve the Obstacle Negotiating Ability of People with Parkinson's Disease: A Preliminary Study. AB - [Purpose] The purpose of this study was to examine the effects of Tai Chi (TC) based exercise on dynamic postural control during obstacle negotiation by subjects with mild or moderate Parkinson's disease (PD). [Subjects] Twelve subjects (mean age, 65.3+/-6.1 years) diagnosed with idiopathic PD were enrolled for this study. [Methods] All the subjects were tested a week before and 12 weeks after the initiation of the TC exercise. In the test, they were instructed to negotiate an obstacle from the position of quiet stance at a normal speed. They were trained with TC exercise that emphasized multidirectional shift in weight bearing from bilateral to unilateral support, challenging the postural stability, three times per week for 12 weeks. Center of pressure (COP) trajectory variables before and after TC exercise were measured using two force plates. [Results] A comparison of the results between pre- and post-intervention showed a statistically significant improvement in anteroposterior and mediolateral displacement of COP. [Conclusion] Twelve weeks of TC exercise may be an effective and safe form of stand-alone behavioral intervention for improving the dynamic postural stability of patients with PD. PMID- 25140089 TI - Effects of visual display terminal works on cervical movement pattern in patients with neck pain. AB - [Purpose] This study examined changes in the onset of neck movement in young adults with and without mild neck pain (MNP) during visual display terminal (VDT) work. [Subjects] Ten control subjects and 10 subjects with MNP who were VDT workers were recruited. The upper (UC) and lower cervical (LC) spine angles in the sagittal plane were collected using an ultrasound-based motion analysis system during VDT work for 5 min. [Results] The MNP group had faster movement initiation in the UC and LC compared with the control group during VDT work. [Conclusion] These findings suggest that young adults with MNP should be cautious when performing VDT work while sitting. PMID- 25140090 TI - Effects of Low-intensity Pulsed Ultrasound and Cryotherapy on Recovery of Joint Function and C-reactive Protein Levels in Patients after Total Knee Replacement Surgery. AB - [Purpose] We investigated the effect of low-intensity pulsed ultrasound and cryotherapy on joint function recovery and C-reactive protein (CRP) levels of patients with total knee replacement. [Subjects] Forty-six patients with total knee replacement were recruited and allocated to either low-intensity pulsed ultrasound therapy (n=15), cryotherapy (n=15), or a combination of both (n=16). Therapy was administered once a day, 5 times a week for 3 weeks. To determine functional joint recovery and reduction of inflammation, changes in the Korean Western Ontario and McMaster Universities Arthritis Index (K-WOMAC), range of motion (ROM), and CRP were assessed postsurgically and four times over a 3-week period. Using one-way analysis of variance (ANOVA), homogeneity tests were performed based on participants' general characteristics. To recognize changes in time-variant K-WOMAC, ROM, and CRP values between groups, repeated measures ANOVA was performed, and Tukey's test was used for post-test analysis. Values at alpha=0.05 were considered significant. [Results] We found a difference between groups and times, and the group that received the combined therapies showed greater changes in outcomes than the group that received low-intensity pulsed ultrasound therapy alone. [Conclusion] Applying both low-intensity pulsed ultrasound and cryotherapy can relieve inflammation and enhance joint function in patients who undergo total knee replacement. PMID- 25140091 TI - Changes in pain, dysfunction, and grip strength of patients with acute lateral epicondylitis caused by frequency of physical therapy: a randomized controlled trial. AB - [Purpose] The purpose of this study was to investigate the changes in pain, dysfunction, and grip strength of patients with acute lateral epicondylitis and to suggest the appropriate treatment frequency and period. [Subjects] The subjects were divided into three: 2 days per week group (n=12), 3 days per week group (n=15), and 6 days per week group (n=13). [Methods] All groups received conventional physical therapy for 40 minutes and therapeutic exercises for 20 minutes per session during 6 weeks. The outcome measurements were the visual analogue scale (VAS), Patient-Rated Tennis Elbow Evaluation (PRTEE), and grip strength. [Results] The results of this study were as follows: at 3 weeks, there were no significant differences in VAS and PRTEE in the 3 groups, but at 6 weeks, 6 days per week group significantly decreased these two outcomes. Grip strength was significantly increased in 3 and 6 days per week groups at 6 weeks. [Conclusion] In conclusion, physical therapy is needed 3 days per week for 3 weeks in patients with acute lateral epicondylitis. After 3 weeks, 6 days per week is the most effective treatment frequency. PMID- 25140092 TI - Difference in the Effect of Outpatient Pulmonary Rehabilitation Due to Variation in the Intervention Frequency: Intervention Centering on Home-based Exercise. AB - [Purpose] The purpose of this study was to investigate differences in effects caused by variation in the intervention frequency of outpatient pulmonary rehabilitation, in terms of the pulmonary function, lower-limb muscle strength, exercise tolerance, and quality of life (QOL). [Subjects and Methods] A total of 36 patients with mild to severe chronic obstructive pulmonary disease (COPD) were studied. These patients were all men over the age of 40 who did not require assistance for activities of daily living (ADL). Groups undergoing intervention once a month (M1 group) and once a week (W1 group) were compared in terms of the effects of outpatient pulmonary rehabilitation for a period of 12 weeks. Intervention during this time included supervised and home-based exercise. [Results] Comparison of before and after intervention revealed that the rate of change in the W1 group was significantly higher than that in the M1 group in terms of the QOL, lower-extremity muscle strength, and 6-minute walking distance. [Conclusion] Outpatient pulmonary rehabilitation programs yielded greater improvements in the W1 group than in the M1 group in terms of the QOL and exercise tolerance. PMID- 25140093 TI - Comparison of the Tibialis Anterior and Soleus Muscles Activities during the Sit to-stand Movement with Hip Adduction and Hip Abduction in Elderly Females. AB - [Purpose] The purpose of this study was to compare the activation of the tibialis anterior (TA) and soleus (SOL) muscles during the sit-to-stand (STS) task with hip adduction and hip abduction in elderly females. [Subjects] We recruited 16 healthy elderly females with no pain in the knee joint and no other orthopedic problems of the lower limbs. [Methods] The activities of the dominant lower extremity muscles were measured using a wireless electromyography (EMG) system. Subjects then performed a total of nine STS trials, including three trials each for hip adduction, hip abduction, and natural STS tasks. [Results] In the pre- thigh-off (TO) phase, the normalized EMG data of the TA muscle increased significantly when the STS task was performed with hip adduction compared with hip abduction. In the post-TO phase, the normalized EMG data of the TA muscle showed a significant increase during the STS task with hip adduction compared with hip abduction. Additionally, the normalized EMG data of the SOL muscle increased significantly when the STS task was performed with hip adduction compared with hip abduction. [Conclusion] Therefore, the STS movement with hip adduction poses a greater challenge for balance control, indicating that certain elderly individuals would have difficulty in executing an abrupt adjustment in their dynamic postural stability during the STS movement. PMID- 25140094 TI - The Effects of Stretching with Lumbar Traction on VAS and Oswestry Scales of Patients with Lumbar 4-5 Herniated Intervertebral Disc. AB - [Purpose] This study investigated the effect of stretching with lumbar traction on VAS and Oswestry scale scores of lumbar 4-5 herniated intervertebral disc (HIVD) patients. [Subjects] We recruited 20 lumbar 4-5 HIVD patients. [Methods] We performed stretching with lumbar traction for lumbar 4-5 HIVD patients during 4 weeks. The VAS and Oswestry scales were measured before and 4 weeks after the intervention. [Results] The results showed a significant decrease in VAS scale scores for stretching with lumbar traction in lumbar 4-5 HIVD patients, from 18+/ 1.29 to 2.1+/-1.35. The Oswestry scale scores also decreased significantly, from 20.35+/-2.01 to 3.5+/-2.84, after stretching with lumbar traction. [Conclusion] Thus, we suggest stretching with lumbar traction for lumbar 4-5 HIVD patients. PMID- 25140095 TI - Peak torque and average power at flexion/extension of the shoulder and knee when using a mouth guard in adults with mild midline discrepancy. AB - [Purpose] This study was conducted to investigate the changes in torque and power during flexion and extension of the shoulder and the knee joints caused by midline correction using mouth guards made from different materials in adults with mild midline discrepancy. [Subjects] The subjects of this study were males (n=12) in their 20s who showed a 3-5 mm difference between the midlines of the upper and lower teeth but had normal masticatory function. [Methods] The torque and average power of the lower limb and upper limb were measured during flexion and extension according to various types of mouth guard. [Results] There were significant differences in relative torque and average power between three conditions (no mouth guard, soft-type mouth guard, and hard-type mouth guard) at shoulder flexion and extension. There were no significant differences in relative torque and average power between the three conditions at knee flexion and extension. [Conclusions] These results suggest that use of a mouth guard is a method by which people with a mild midline discrepancy can improve the stability of the entire body. PMID- 25140096 TI - The Effects of Lower Extremity Angle According to Heel-height Changes in Young Ladies in Their 20s during Gait. AB - [Purpose] The purpose of this study was to compare the effects of heel-height changes on the low joint angles of the lower extremities of women in their 20s during gait. [Subjects and Methods] Qualisys Track Manager Software ver. 2.8 (Qualisys, Sweden) was used to perform measurements on 14 female university students in their 20s. To measure movements, the subjects were asked to walk while wearing high-heeled shoes and reflective stickers on their hip joints, knee joints, and ankle joints, the changes in joint angles were measured at heel strike, foot flat, and toe off. [Results] Analysis of the amount of change according to heel height changes during gait showed that the angle of the hip joints was reduced with an increase in heel-height. Although the changes were not significant, the angle of the knee joints was reduced during heel strike, foot flat, and midstance, and it was increased during toe off. In contrast, the angle of the ankle joints was increased by a significant amount during heel strike, foot flat, midstance, and toe off. [Conclusions] During gait with high heels, the movements of the lower extremities of women in their 20s were reduced significantly with an increase in heel height. Therefore, it is concluded that the restrictions on gait can only be reduced by wearing low-heeled shoes. PMID- 25140097 TI - Anaerobic Threshold and Salivary alpha-amylase during Incremental Exercise. AB - [Purpose] The purpose of this study was to clarify the validity of salivary alpha amylase as a method of quickly estimating anaerobic threshold and to establish the relationship between salivary alpha-amylase and double-product breakpoint in order to create a way to adjust exercise intensity to a safe and effective range. [Subjects and Methods] Eleven healthy young adults performed an incremental exercise test using a cycle ergometer. During the incremental exercise test, oxygen consumption, carbon dioxide production, and ventilatory equivalent were measured using a breath-by-breath gas analyzer. Systolic blood pressure and heart rate were measured to calculate the double product, from which double-product breakpoint was determined. Salivary alpha-amylase was measured to calculate the salivary threshold. [Results] One-way ANOVA revealed no significant differences among workloads at the anaerobic threshold, double-product breakpoint, and salivary threshold. Significant correlations were found between anaerobic threshold and salivary threshold and between anaerobic threshold and double product breakpoint. [Conclusion] As a method for estimating anaerobic threshold, salivary threshold was as good as or better than determination of double-product breakpoint because the correlation between anaerobic threshold and salivary threshold was higher than the correlation between anaerobic threshold and double product breakpoint. Therefore, salivary threshold is a useful index of anaerobic threshold during an incremental workload. PMID- 25140098 TI - The Effect of a PNF Technique Program after Mastectomy on Lymphedema Patients' Depression and Anxiety. AB - [Purpose] This study was conducted to examine the effects of exercises applied with PNF techniques performed for 30 minutes per session, three times per week, after receipt of radiation therapy following mastectomy on depression and anxiety in patients diagnosed with lymphedema and to prepare basic data for creation of self-directed exercise programs for lymphedema patients that will enable them to perform exercises within the range of no pain. [Methods] The subjects of this study were 45 patients selected from among those diagnosed with breast cancer who showed lymphedema after anti-cancer therapy following mastectomy. [Results] The Beck depression score changed significantly during the five assessment periods however, there was no significant difference between the treatment groups. Post hoc analyses revealed that there was significant improvement in the Beck depression score from 4 weeks in all three groups. The interaction between group and time was also statistically significant. [Conclusion] In conclusion, PNF techniques helped to improve the depression and anxiety rates. Four weeks after the start of therapy, PNF techniques Depression and anxiety to create a greater degree of decline was on display. PMID- 25140100 TI - The Change in Knee Angle during the Gait by Applying Elastic Tape to the Skin. AB - [Purpose] The aim of this study was to verify how the application of elastic tape to the anterior surface of the thigh changes the knee angle pattern during gait. [Subjects] The subjects were 10 people who showed an abnormal knee angle change pattern during usual walking. They did not show the so-called double knee action. [Methods] Subjects were asked to walk as usual, and then to walk with elastic tape attached to the anterior surface of the thigh. The knee angle was measured during gait with an electronic goniometer. We graphed the temporal changes of the knee angle and compared them with the normal gait pattern. [Results] The knee angle gait pattern of six of the 10 subjects improved after application of the tape and became like a normal gait pattern. The changes in the knee angle resulted from a stimulus via the skin, rather than voluntary muscular adjustment, suggesting that the changes may have originated due to differences in reflexive tensile strength. [Conclusion] In normal speed gait, it is suggested that the knee angle was altered such that it exhibited a normal pattern by applying elastic tape to the anterior surface of the thigh. We suspect that application of the elastic tape may change the muscle tonus. PMID- 25140099 TI - Influence of motor imagery of isometric opponens pollicis activity on the excitability of spinal motor neurons: a comparison using different muscle contraction strengths. AB - [Purpose] This study aimed to determine the differences in the excitability of spinal motor neurons during motor imagery of a muscle contraction at different contraction strengths. [Methods] We recorded the F-wave in 15 healthy subjects. First, in a trial at rest, the muscle was relaxed during F-wave recording. Next, during motor imagery, subjects were instructed to imagine maximum voluntary contractions of 10%, 30%, and 50% while holding the sensor of a pinch meter, and F-waves were recorded for each contraction. F-waves were recorded immediately and at 5, 10, and 15 min after motor imagery. [Results] Both persistence and F/M amplitude ratios during motor imagery under maximum voluntary contractions of 10%, 30%, and 50% were significantly higher than that at rest. In addition, persistence, F/M amplitude ratio, and latency were similar during motor imagery under the three muscle contraction strengths. [Conclusion] Motor imagery under maximum voluntary contractions of 10%, 30%, and 50% can increase the excitability of spinal motor neurons. The results indicated that differences in muscle contraction strengths during motor imagery are not involved in changes in the excitability of spinal motor neurons. PMID- 25140101 TI - The effects of elbow joint angle changes on elbow flexor and extensor muscle strength and activation. AB - [Purpose] This research investigated the relationship between elbow joint angle and elbow flexor and extensor strength and activation, taking into consideration the length-tension tension curve of the muscle. [Subjects] There were 30 research subjects in total, 15 male and 15 female college students from Busan S University who had no functional disabilities that might affect measurement of muscle strength and muscle activation, and none had they experienced any damage in their upper extremities or hands. [Methods] The elbow joint angles were positioned at angles of 56 degrees , 70 degrees and 84 degrees , and then muscle strength and activation were compared. Repeated measures ANOVA was used for statistical analysis, and the paired t-test was used to identify the difference between each angle. We used the SPSS for windows (ver. 21.0) statistical software and a significance level of alpha=0.05. [Results] The results showed that muscle strength and activation of the biceps was highest when the joint was placed at 56 degrees . On the other hand, for the triceps, the result was highest when the joint angle was placed at 84 degrees . [Conclusion] The tests confirmed that muscle strength and activation were highest at the joint angle at which the muscle was stretched to 20% more than the resting position in concentric contraction. PMID- 25140102 TI - Effect of whole body vibration exercise in the horizontal direction on balance and fear of falling in elderly people: a pilot study. AB - [Purpose] The purpose of the present study was to investigate the effects of whole body vibration exercise in the horizontal direction on balance and fear of falling in the elderly. [Methods] This study was a case series of 17 elderly individuals. Participants performed whole body vibration exercise in the horizontal direction using a whole body vibration device for 15 minutes a day, 3 times a week, for 6 weeks. At baseline and after the 6-week intervention, balance was measured using the Berg Balance Scale and Timed Up and Go test, and fear of falling was assessed using the Falls Efficacy Scale. [Results] After the intervention, significant improvements from baseline values in the Berg Balance Scale, Timed Up and Go test, and Falls Efficacy Scale were observed in the study participants. [Conclusion] Elderly individuals who performed whole body vibration exercise in the horizontal direction showed significant improvements in balance and fear of falling. However, the observed benefits of whole body vibration exercise in the horizontal direction need to be confirmed by additional studies. PMID- 25140103 TI - Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli. AB - [Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group * type of stimulus * first stimulus interaction was observed for the extent of reaction, significant type of stimulus * first stimulus interaction was noted for the extent of reaction. For an 80 dB 6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli. PMID- 25140104 TI - Is There Any Relationship between Joint Destruction and Carotid Intima-media Thickness in Patients with Rheumatoid Arthritis? AB - [Purpose] The purpose of this study was to investigate the possible relationship between joint destruction and carotid intima-media thickness in patients with rheumatoid arthritis. [Subjects and Methods] Thirty-four RA patients and 31 healthy controls were enrolled in this study. The disease activity for 28 joints was recorded for each patient using the erythrocyte sedimentation rate (DAS28ESR), a visual analog scale (VAS0-10 cm), and a disability index, the health assessment questionnaire (HAQ). X-ray imagesof the patients were scored according to the modified Sharp/van der Heijde method, and the common carotid intimal medial thickness (CIMT) was automatically measured with software using high-resolution Doppler ultrasound. [Results] Contrary to our hypothesis, the modified total Sharp score (mTSS) and CIMT were not significantly associated. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels of the RA patients and the right CIMT, left CIMT, and mean CIMT scores were significantly elevated. Positive correlation was detected between the mean CIMT score and age, CRP levels, LDL concentration and triglycerides (TG) level. In the regression model, where the mean CIMT was the independent variable and age, CRP, LDL, and TG were dependent variables, age was found to be an independent predictor of CIMT. [Conclusions] Patients suffering from RA require close monitoring for cardiovascular risks, and the comorbidity of age-related cardiovascular disease should not be overlooked. PMID- 25140106 TI - The effects of aerobic exercise and strengthening exercise on pain pressure thresholds. AB - [Purpose] We assessed the effects of aerobic exercise and strengthening exercise on pain pressure thresholds (PPTs) over time. [Subjects and Methods] Fifteen healthy participants were recruited and randomly divided into 3 groups: aerobic exercise, strengthening exercise, and control. The subjects in the aerobic group walked on a treadmill for 40 min at 6.5 km/h. The subjects in the strength group performed circuit training that included bench press, lat pull down, biceps curl, triceps extension, and shoulder press based on the perceived exertion for 40 min. The subjects in the control group rested without any exercise in a quiet room for 40 min. The PPTs of 5 potential muscle trigger points before exercise, and immediately after 10 and 40 min of exercise or rest were measured using an electronic algometer (JTECH Medical, USA). The Friedman's, Kruskal-Wallis, and Mann-Whitney tests were performed using SPSS 18.0 (IBM, Korea). [Results] The PPTs of all subjects decreased after 10 min of exercise, but the difference was not statistically significant. The PPTs of the control group decreased after 40 min. Furthermore, the PPTs of 3 muscles increased after 40 min of aerobic exercise and of 6 muscles after 40 min of strengthening exercise. No significant difference in PPTs was noted among the groups. [Conclusion] The results show that 40 min is a more appropriate exercise time, although the efficacy of controlling pain did not differ between strengthening exercise and aerobic exercise. PMID- 25140105 TI - Functional Capacity of Oldest Old Living in a Long-stay Institution in Rio De Janeiro, Brazil. AB - [Purpose] A significant increase in the number of oldest old has occurred worldwide. The aim of this study was to characterize the functional capacity of the oldest old residents in a long-stay institution in Rio de Janeiro, Brazil. [Subjects and Methods] All participants were evaluated according to the following metrics: anthropometry, body composition (bioelectrical impedance), handgrip strength, balance (Berg scale and stabilometry), ankle mobility (electrogoniometry), physical capacity (six-minute walk test), quality of life (WHOQOL-OLD), and dietary habits (questionnaire). [Results] Twenty elderly subjects with a mean age of 85.75 +/- 5.22 years and a mean fat percentage of 39.02 +/- 5.49% participated in the study. The group at risk of falls (n = 8) had a lower handgrip strength and walked a shorter distance over the course of six minutes compared with the group not at risk of falls. The obese group (n = 15) had higher values for stabilometric variables than the nonobese group. There was a positive and significant correlation between ankle joint mobility and physical capacity (r = 0.47). [Conclusion] High values for obesity and low values for handgrip strength and physical capacity were associated with worse body balance. Low values for ankle mobility were also associated with worse physical capacity in this population. PMID- 25140107 TI - Clinical Study of Respiratory Function and Difference in Pneumonia History between Alzheimer's Disease and Vascular Dementia Groups. AB - [Purpose] This study compared respiratory function and differences in pneumonia history between Alzheimer's disease and vascular dementia groups. [Subjects] Fifty-eight inpatients in the dementia treatment ward in a psychiatric facility were enrolled. [Methods] Patients underwent respiratory function testing twice using an 80-cm party horn. The Mini-Mental State Examination was also performed and motor functions were evaluated. Patient characteristics were obtained from medical records. [Results] Significant differences were noted between Alzheimer's disease and vascular dementia groups in the ability to blow the party horn to full length, pneumonia history, and presence of impaired mobility. [Conclusion] Party horn evaluation may be useful for determining the risk of pneumonia in patients with dementia. PMID- 25140109 TI - The psychometric properties of the clock drawing test in South Korea. AB - [Purpose] The aims of the present study were to analyze the validity and reliability of the Clock Drawing Test (CDT) as a screening tool for cognitive impairments in both stroke patients and older adults in South Korea. [Subjects and Methods] Forty-three stroke patients and 42 elderly residents living in urban communities were recruited. They were divided into three groups according to K MMSE scores. Kruskal-Wallis one-way ANOVA was used for construct validity, Friedman two-way ANOVA for discriminative validity, and Spearman's rank order correlation coefficient for inter-rater reliability. [Results] Regardless of groups, construct and discriminative validity tests showed statistically significant results, and Spearman's rho was over 0.56. [Discussion] CDT demonstrated acceptable validity and reliability. CDT using the productive methods and Freedman's scoring systems may be suitable for cognitive decrease in stroke patients and the elderly. PMID- 25140108 TI - Brain Activity Associated with the Illusion of Motion Evoked by Different Vibration Stimulation Devices: An fNIRS Study. AB - [Purpose] A number of different stimulation devices are used in basic and clinical research studies, and their frequencies of use vary. However, whether or not they are equally effective has not been investigated. The purpose of the present study was to investigate neural activity in the brain during the illusion of motion evoked by stimulating the tendons of the wrist extensor muscles using various vibration devices. [Subjects] Twelve right-handed university students with no history of nervous system disorder or orthopedic disease participated in the study. [Methods] The wrist extensor tendon was stimulated using 3 different devices: 1) a vibration stimulation device (SL-0105 LP; Asahi Seisakusho Co., Ltd., Saitama, Japan), frequency 80 Hz; 2) a handy massager (YCM-20; Yamazen Corporation, Osaka, Japan), frequency 70 Hz; and 3) a handy massager (Thrive MD 01; Thrive Co., Ltd., Osaka, Japan), frequency 91.7 Hz. Brain activity was recorded during stimulation by using functional near-infrared spectroscopy. [Results] Increased neural activity was observed in both the premotor cortices and the parietal region in both hemispheres in all 3 cases. The level and localization of neural activity was comparable for all 3 stimulation devices used. [Conclusion] This suggests that subjects experience the illusion of motion while the tendon is being stimulated using any vibration device. PMID- 25140110 TI - Evaluation of Cranio-cervical Posture in Children with Bruxism Before and After Bite Plate Therapy: A Pilot Project. AB - [Purpose] The aim of the present study was to evaluate the effect of a biteplate on the cranio-cervical posture of children with bruxism. [Subjects and Methods] Twelve male and female children aged six to 10 years with a diagnosis of bruxism participated in this study. The children used a biteplate during sleep for 30 days and were submitted to three postural evaluations: initial, immediately following placement of the biteplate, and at the end of treatment. Posture analysis was performed with the aid of the Alcimagem((r)) 2.1 program. Data analysis (IBM SPSS Statistics 2.0) involved descriptive statistics and the Student's t-test. [Results] A statistically significant difference was found between the initial cranio-cervical angle and the angle immediately following placement of the biteplate. However, no statistically significant difference was found between the initial angle and the angle after one month of biteplate usage. [Conclusion] No significant change in the cranio-cervical posture of the children was found one month of biteplate usage. However, a reduction occurred in the cranio-cervical angle when the biteplate was in position. PMID- 25140111 TI - Body responses to sound stimulation: a crossover study. AB - [Purpose] Auditory stimulation is used for the functional assessment of the saccule and saccule-derived vestibule-cervical reflex in clinical environments. The present study aimed to clarify the influences of sound stimulation as a type of auditory stimulation on the body. [Subjects] The subjects were nine healthy youths (2 males and 7 females). [Methods] FFD, FRT, the muscle hardness of hamstrings, and RT were measured after the sound stimulation of 1,000 Hz and 70dB. [Results] RT was markedly shortened, and the FFD significantly increased with sound stimulation. [Conclusion] Sound stimulation improved the RT and flexibility, possibly resulting in an effective approach in physical therapy. PMID- 25140112 TI - Effects of tai chi for patients with knee osteoarthritis: a systematic review. AB - [Purpose] The aim of the present study was to seek evidence for the effectiveness of Tai Chi for patients with knee osteoarthritis (KOA). [Subjects and Methods] Systematic searches were conducted of the China Journals Full-text Database, Pubmed, Medline, Science Direct-Online Journals and CINAHL for studies published between 2000 and 2012. Studies were evaluated based on following inclusion criteria: 1) design: randomized control, clinical trial; 2) subjects: patients with a knee osteoarthritis diagnosis; 3) intervention: exercise involving Tai Chi; 4) studies published in English or Chinese. [Results] Six randomized control studies involving Tai Chi and knee osteoarthritis were found. [Conclusion] Tai Chi was an effective way of relieving pain and improving physical function. Further randomized controlled trials with large sample sizes and long training period are needed to compare groups who perform Tai Chi training with other groups who undergo other forms of physical exercise in order to confirm the efficacy of Tai Chi. PMID- 25140113 TI - Cross-generational vowel change in American English. AB - This study examines cross-generational changes in the vowel systems in central Ohio, southeastern Wisconsin and western North Carolina. Speech samples from 239 speakers, males and females, were divided into three age groups: grandparents (66 91 years old), parents (35-51) and children (8-12). Acoustic analysis of vowel dynamics (i.e., formant movement) was undertaken to explore variation in the amount of spectral change for each vowel. A robust set of cross-generational changes in /i, epsilon, ae, alpha/ was found within each dialect-specific vowel system, involving both their positions and dynamics. With each successive generation, /i, epsilon, ae/ become increasingly monophthongized and /alpha/ is diphthongized in children. These changes correspond to a general anticlockwise parallel rotation of vowels (with some exceptions in /i/ and /epsilon/). Given the widespread occurrence of these parallel chain-like changes, we term this development the "North American Shift" which conforms to the general principles of chain shifting formulated by Labov (1994) and others. PMID- 25140114 TI - Rotenone remarkably attenuates oxidative stress, inflammation, and fibrosis in chronic obstructive uropathy. AB - Mitochondrial abnormality has been shown in many kidney disease models. However, its role in the pathogenesis of chronic kidney diseases (CKDs) is still uncertain. In present study, a mitochondrial complex I inhibitor rotenone was applied to the mice subjected to unilateral ureteral obstruction (UUO). Following 7-days rotenone treatment, a remarkable attenuation of tubular injury was detected by PAS staining. In line with the improvement of kidney morphology, rotenone remarkably blunted fibrotic response as shown by downregulation of fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), collagen I, collagen III, and alpha-SMA, paralleled with a substantial decrease of TGF-beta 1. Meanwhile, the oxidative stress markers thiobarbituric acid-reactive substances (TBARS) and heme oxygenase 1 (HO-1) and inflammatory markers TNF-alpha, IL-1beta, and ICAM-1 were markedly decreased. More importantly, the reduction of mitochondrial DNA copy number and mitochondrial NADH dehydrogenase subunit 1 (mtND1) expression in obstructed kidneys was moderately but significantly restored by rotenone, suggesting an amelioration of mitochondrial injury. Collectively, mitochondrial complex I inhibitor rotenone protected kidneys against obstructive injury possibly via inhibition of mitochondrial oxidative stress, inflammation, and fibrosis, suggesting an important role of mitochondrial dysfunction in the pathogenesis of obstructive kidney disease. PMID- 25140115 TI - Tumor necrosis factor is a therapeutic target for immunological unbalance and cardiac abnormalities in chronic experimental Chagas' heart disease. AB - BACKGROUND: Chagas disease (CD) is characterized by parasite persistence and immunological unbalance favoring systemic inflammatory profile. Chronic chagasic cardiomyopathy, the main manifestation of CD, occurs in a TNF-enriched milieu and frequently progresses to heart failure. AIM OF THE STUDY: To challenge the hypothesis that TNF plays a key role in Trypanosoma cruzi-induced immune deregulation and cardiac abnormalities, we tested the effect of the anti-TNF antibody Infliximab in chronically T. cruzi-infected C57BL/6 mice, a model with immunological, electrical, and histopathological abnormalities resembling Chagas' heart disease. RESULTS: Infliximab therapy did not reactivate parasite but reshaped the immune response as reduced TNF mRNA expression in the cardiac tissue and plasma TNF and IFNgamma levels; diminished the frequency of IL-17A(+) but increased IL-10(+) CD4(+) T-cells; reduced TNF(+) but augmented IL-10(+) Ly6C(+) and F4/80(+) cells. Further, anti-TNF therapy decreased cytotoxic activity but preserved IFNgamma-producing VNHRFTLV-specific CD8(+) T-cells in spleen and reduced the number of perforin(+) cells infiltrating the myocardium. Importantly, Infliximab reduced the frequency of mice afflicted by arrhythmias and second degree atrioventricular blocks and decreased fibronectin deposition in the cardiac tissue. CONCLUSIONS: Our data support that TNF is a crucial player in the pathogenesis of Chagas' heart disease fueling immunological unbalance which contributes to cardiac abnormalities. PMID- 25140116 TI - Cell death-associated molecular-pattern molecules: inflammatory signaling and control. AB - Apoptosis, necroptosis, and pyroptosis are different cellular death programs characterized in organs and tissues as consequence of microbes infection, cell stress, injury, and chemotherapeutics exposure. Dying and death cells release a variety of self-proteins and bioactive chemicals originated from cytosol, nucleus, endoplasmic reticulum, and mitochondria. These endogenous factors are named cell death-associated molecular-pattern (CDAMP), damage-associated molecular-pattern (DAMP) molecules, and alarmins. Some of them cooperate or act as important initial or delayed inflammatory mediators upon binding to diverse membrane and cytosolic receptors coupled to signaling pathways for the activation of the inflammasome platforms and NF-kappaB multiprotein complexes. Current studies show that the nonprotein thiols and thiol-regulating enzymes as well as highly diffusible prooxidant reactive oxygen and nitrogen species released together in extracellular inflammatory milieu play essential role in controlling pro- and anti-inflammatory activities of CDAMP/DAMP and alarmins. Here, we provide an overview of these emerging concepts and mechanisms of triggering and maintenance of tissue inflammation under massive death of cells. PMID- 25140117 TI - Peritoneal air exposure elicits an intestinal inflammation resulting in postoperative ileus. AB - BACKGROUND: The pathogenesis of postoperative ileus (POI) is complex. The present study was designed to investigate the effects of peritoneal air exposure on the POI intestinal inflammation and the underlying mechanism. METHODS: Sprague-Dawley rats were randomized into five groups (6/group): the control group, the sham group, and three exposure groups with peritoneal air exposure for 1, 2, or 3 h. At 24 h after surgery, we analyzed the gastrointestinal transit, the serum levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10, the myeloperoxidase activity, and the levels of TNF-alpha, IL-1beta, IL-6, and IL 10 in the ileum and colon. The oxidant and antioxidant levels in the ileum and colon were analyzed by measuring malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). RESULTS: Peritoneal air exposure caused an air-exposure-time-dependent decrease in the gastrointestinal transit. The length of peritoneal air exposure is correlated with the severity of both systemic and intestinal inflammations and the increases in the levels of MDA, SOD, GSH-Px, and T-AOC. CONCLUSIONS: The length of peritoneal air exposure is proportional to the degree of intestinal paralysis and the severity of intestinal inflammation, which is linked to the oxidative stress response. PMID- 25140118 TI - Combined first-trimester screening in northern Finland: experiences of the first ten years. AB - OBJECTIVE: To evaluate the efficacy of first trimester combined screening for Down's syndrome in Northern Finland during the first 10 years of practice. METHODS: During 1 January 2002 to 31 December 2011, 47,896 women participated voluntarily in combined screening during first trimester. The risk cutoff was 1:250. The study period was divided into two time periods; 2002-2006 and 2007 2011. RESULTS: During the first half of the study period, the detection rate (DR) was 77.3% with a 4.9% false-positive rate (FPR). During the latter half, the DR was 77.1% with a 2.8% FPR. CONCLUSIONS: An important issue is the number of invasive procedures needed to detect one case of Down's syndrome. The screening performance improved markedly in the latter five years period since the FPR lowered from 4.9% to 2.8% and the number of invasive procedures needed to detect one case of Down's syndrome lowered from 15 to 11. PMID- 25140120 TI - Consecutively preparing d-xylose, organosolv lignin, and amorphous ultrafine silica from rice husk. AB - Rice husk is an abundant agricultural by-product reaching the output of 80 million tons annually in the world. The most common treatment method of rice husk is burning or burying, which caused serious air pollution and resource waste. In order to solve this problem, a new method is proposed to comprehensively utilize the rice husk in this paper. Firstly, the D-xylose was prepared from the semicellulose via dilute acid hydrolysis. Secondly, the lignin was separated via organic solvent pulping from the residue. Finally, the amorphous ultrafine silica was prepared via pyrolysis of the residue produced in the second process. In this way, the three main contents of rice husk (semicellulose, lignin, and silica) are consecutively converted to three fine chemicals, without solid waste produced. The yields of D-xylose and organosolv lignin reach 58.2% and 58.5%, respectively. The purity and specific surface of amorphous ultrafine silica reach 99.92% and 225.20 m(2)/g. PMID- 25140119 TI - A qualitative investigation of the roles and perspectives of older patients with advanced cancer and their family caregivers in managing pain in the home. AB - BACKGROUND: Pain in advanced cancer is complex and multifaceted. In older patients comorbidities and age-related functional decline add to the difficulties in managing cancer pain. The current emphasis on care in the community, and preference by patients with life-limiting disease to receive care in the home, has meant that patients and their family caregivers have become increasingly responsible for the day-to-day management of cancer pain. An appreciation of patients' and caregivers' roles and perspectives managing pain is, therefore, fundamental to addressing cancer pain in this setting. Consequently, we sought to explore and describe their perspectives and roles. METHODS: A qualitative descriptive approach was used. Semi-structured interviews were conducted with a purposeful sample of patient- family caregiver dyads. Participants included 18 patients aged 65 years and over, with advanced cancer, receiving palliative care at home, and 15 family caregivers. The interview data were analysed using thematic analyses. Strategies were used to establish rigour. RESULTS: Two main themes were identified. The first theme, "Communicating the pain", represented pain assessment and incorporated four subthemes in which participants described: their roles in pain assessment, the identification and expression of pain, and the communication of pain between patients and caregivers. The second theme, "Finding a solution", comprised of four subthemes that reflected participants' roles and approaches in controlling pain; as well as their beliefs about cancer pain control, experience with side effects, and perspectives on the goals of treatment. CONCLUSIONS: The findings support other studies in identifying knowledge and attitudinal barriers to pain control; while adding to the literature by highlighting practical and relational barriers faced by older patients and their family caregivers. Health care professionals can do much to address the barriers identified by: correcting misconceptions regarding cancer pain, facilitating the communication of pain within dyads, and ensuring that patients and family caregivers have the knowledge, skills, and ability to assess and implement pain treatment strategies. This support needs to be individually tailored to meet the ongoing needs of both members of the dyad so that the shared goals of pain management are accomplished. PMID- 25140121 TI - Synthesis and Spectroscopic Characterization of Some New Axially Ligated Indium(III) Macrocyclic Complexes and Their Biological Activities. AB - The synthesis and spectroscopic characterization of new axially ligated indium(III) porphyrin complexes were reported. Chloroindium(III) porphyrin (TPPIn Cl) was obtained in good yield by treating the corresponding free base with indium trichloride. The action of the different phenols on chloroderivatives (TPPIn-Cl) led to the corresponding phenolato complexes (TPPIn-X). These derivatives were characterized on the basis of mass spectrometry, (1)H-NMR, IR, and UV-visible data. The separation and isolation of these derivatives have been achieved through chromatography. The spectral properties of free base porphyrin and its corresponding metallated and axially ligated indium(III) porphyrin compounds were compared with each other. A detailed analysis of UV-Vis, (1)H-NMR, and IR suggested the transformation from free base porphyrin to indium(III) porphyrin. Besides, (13)C-NMR and fluorescence spectra were also reported and interpreted. The stability of these derivatives has also been studied through thermogravimetry. The complexes were also screened for anticancerous activities. Among all the complexes, 4-MePhO-InTPP shows highest anticancerous activity. The title complexe, TPPIn-X (where X = different phenolates), represents a five coordinate indium(III) porphyrin complex in a square-pyramidal geometry with the phenolate anion as the axial ligand. PMID- 25140122 TI - Determination of the total mass of antioxidant substances and antioxidant capacity per unit mass in serum using redox titration. AB - Objective. Total antioxidant capacity in serum is determined by the total mass of antioxidant substances and the antioxidant capacity per unit mass (average activity). The purpose of this study was to develop a method to determine the mass of antioxidant substances and average activity in human serum. Methods. Specimens of serum were collected from 100 subjects each from two different age groups: over 75 years old and 20-40 years old. The test serum was diluted into a series of concentrations, following which standard oxidation agents (KMnO4 for potassium permanganate method and I2 for iodimetry) were added to each concentration of serum, and the absorbance of the mixture (optical density, OD) was measured. The OD value and logarithm of dilution factor (lgT) at the end of the titration were obtained, from which the lgT could be considered as mass of antioxidant substances (M). Total antioxidant capacity (Ta) was calculated with the equation Ta = 100/(OD1 + 2 * OD2 + 2 * OD3 + 2 * OD4 + OD5), and average activity (A) was calculated as A = Ta/M. Results. The potassium permanganate method generated similar results to the iodimetric method. Compared with the younger group, total antioxidant capacity in the over-75-year age group was found to be significantly reduced, along with a decrease in the mass of antioxidant substances and average activity levels in human serum. Conclusions. The approach described in this paper is suitable for determining the average activity and mass of antioxidant substances in human serum. PMID- 25140123 TI - Socioeconomic differences in selected dietary habits among Norwegian 13-14 year olds: a cross-sectional study. AB - BACKGROUND: Social inequalities in health are a major and even growing problem in all European countries. OBJECTIVE: The aim of the present study was to describe 1) differences in dietary habits among Norwegian adolescents by gender and socioeconomic status; 2) differences in self-reported knowledge of dietary guidelines among their parents according to socioeconomic status. DESIGN: In 2012, a cross-sectional study where students filled in a web-based food frequency questionnaire at school was conducted in nine lower secondary schools in Vest Agder County, Norway. Socioeconomic status (SES) and knowledge of dietary guidelines were obtained from the parents using a web-based questionnaire. In total, 517 ninth-grade students (mean age 13.9) out of 742 invited students participated in the study, giving a participation rate of 69.7%. The total number of dyads with information on both parents and students was 308 (41.5%). RESULTS: The findings indicate that there is a tendency for girls to have a healthier diet than boys, with greater intake of fruits and vegetables (girls intake in median 3.5 units per day and boys 2.9 units per day), and lower intake of soft drinks (girls 0.25 l in median versus boys 0.5 l per week). Students from families with higher SES reported a significant higher intake of vegetables and fish, and lower intake of soft drinks and fast food than those from lower SES. Parents with higher SES reported a significantly better knowledge of dietary guidelines compared to those with lower SES. CONCLUSIONS: Differences in dietary habits were found between groups of students by gender and SES. Differences were also found in parents' self-reported knowledge of dietary guidelines. This social patterning should be recognized in public health interventions. PMID- 25140124 TI - A comparative study of drift diffusion and linear ballistic accumulator models in a reward maximization perceptual choice task. AB - We present new findings that distinguish drift diffusion models (DDMs) from the linear ballistic accumulator (LBA) model as descriptions of human behavior in a two-alternative forced-choice reward maximization (Rmax) task. Previous comparisons have not considered Rmax tasks, and differences identified between the models' predictions have centered on practice effects. Unlike the parameter free optimal performance curves of the pure DDM, the extended DDM and LBA predict families of curves depending on their additional parameters, and those of the LBA show significant differences from the DDMs, especially for poorly discriminable stimuli that incur high error rates. Moreover, fits to behavior reveal that the LBA and DDM provide different interpretations of behavior as stimulus discriminability increases. Trends for threshold setting (caution) in the DDMs are consistent between fits, while in the corresponding LBA fits, thresholds interact with distributions of starting points in a complex manner that depends upon parameter constraints. Our results suggest that reinterpretation of LBA parameters may be necessary in modeling the Rmax paradigm. PMID- 25140126 TI - Sex differences in self-regulation: an evolutionary perspective. AB - Bjorklund and Kipp (1996) provide an evolutionary framework predicting that there is a female advantage in inhibition and self-regulation due to differing selection pressures placed on males and females. The majority of the present review will summarize sex differences in self-regulation at the behavioral level. The neural and hormonal underpinnings of this potential sexual dimorphism will also be investigated and the results of the experiments summarized will be related to the hypothesis advanced by Bjorklund and Kipp (1996). Paradoxically, sex differences in self-regulation are more consistently reported in children prior to the onset of puberty. In adult cohorts, the results of studies examining sex differences in self-regulation are mixed. A few recent experiments suggesting that females are less impulsive than males only during fertile stages of the menstrual cycle will be reviewed. A brief discussion of an evolutionary framework proposing that it is adaptive for females to employ a self-regulatory behavioral strategy when fertile will follow. PMID- 25140125 TI - Sexual attractiveness of male chemicals and vocalizations in mice. AB - Male-female interaction is important for finding a suitable mating partner and for ensuring reproductive success. Male sexual signals such as pheromones transmit information and social and sexual status to females, and exert powerful effects on the mate preference and reproductive biology of females. Likewise, male vocalizations are attractive to females and enhance reproductive function in many animals. Interestingly, females' preference for male pheromones and vocalizations is associated with their genetic background, to avoid inbreeding. Moreover, based on acoustic cues, olfactory signals have significant effects on mate choice in mice, suggesting mate choice involves multisensory integration. In this review, we synopsize the effects of both olfactory and auditory cues on female behavior and neuroendocrine functions. We also discuss how these male signals are integrated and processed in the brain to regulate behavior and reproductive function. PMID- 25140128 TI - Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E mediated cholesterol trafficking in neuroblastoma cell lines. AB - Alteration in cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative disorders. Apolipoprotein E (ApoE) is the major component of brain lipoproteins supporting cholesterol transport. We previously reported that the acute-phase protein Haptoglobin (Hpt) binds ApoE, and influences its function in blood cholesterol homeostasis. Major aim of this study was to investigate whether Hpt influences the mechanisms by which cholesterol is shuttled from astrocytes to neurons. In detail it was studied Hpt effect on ApoE dependent cholesterol efflux from astrocytes and ApoE-mediated cholesterol incorporation in neurons. We report here that Hpt impairs ApoE-mediated cholesterol uptake in human neuroblastoma cell line SH-SY5Y, and limits the toxicity of a massive concentration of cholesterol for these cells, while it does not affect cholesterol efflux from the human glioblastoma-astrocytoma cell line U 87 MG. As aging is the most important non-genetic risk factor for various neurodegenerative disorders, and our results suggest that Hpt modulates ApoE functions, we evaluated the Hpt and ApoE expression profiles in cerebral cortex and hippocampus of adolescent (2 months), adult (5 and 8 months), and middle-aged (16 months) rats. Hpt mRNA level was higher in hippocampus of 8 and 16 month-old than in 2-month old rats (p < 0.05), and Hpt concentration increased with the age from adolescence to middle-age (p < 0.001). ApoE concentration, in hippocampus, was higher (p < 0.001) in 5 month-old rats compared to 2 month but did not further change with aging. No age-related changes of Hpt (protein and mRNA) were found in the cortex. Our results suggest that aging is associated with changes, particularly in the hippocampus, in the Hpt/ApoE ratio. Age-related changes in the concentration of Hpt were also found in human cerebrospinal fluids. The age related changes might affect neuronal function and survival in brain, and have important implications in brain pathophysiology. PMID- 25140129 TI - Changes in complex spike activity during classical conditioning. AB - The cerebellar cortex is necessary for adaptively timed conditioned responses (CRs) in eyeblink conditioning. During conditioning, Purkinje cells acquire pause responses or "Purkinje cell CRs" to the conditioned stimuli (CS), resulting in disinhibition of the cerebellar nuclei (CN), allowing them to activate motor nuclei that control eyeblinks. This disinhibition also causes inhibition of the inferior olive (IO), via the nucleo-olivary pathway (N-O). Activation of the IO, which relays the unconditional stimulus (US) to the cortex, elicits characteristic complex spikes in Purkinje cells. Although Purkinje cell activity, as well as stimulation of the CN, is known to influence IO activity, much remains to be learned about the way that learned changes in simple spike firing affects the IO. In the present study, we analyzed changes in simple and complex spike firing, in extracellular Purkinje cell records, from the C3 zone, in decerebrate ferrets undergoing training in a conditioning paradigm. In agreement with the N-O feedback hypothesis, acquisition resulted in a gradual decrease in complex spike activity during the conditioned stimulus, with a delay that is consistent with the long N-O latency. Also supporting the feedback hypothesis, training with a short interstimulus interval (ISI), which does not lead to acquisition of a Purkinje cell CR, did not cause a suppression of complex spike activity. In contrast, observations that extinction did not lead to a recovery in complex spike activity and the irregular patterns of simple and complex spike activity after the conditioned stimulus are less conclusive. PMID- 25140131 TI - Measuring F-actin properties in dendritic spines. AB - During the last decade, numerous studies have demonstrated that the actin cytoskeleton plays a pivotal role in the control of dendritic spine shape. Synaptic stimulation rapidly changes the actin dynamics and many actin regulators have been shown to play roles in neuron functionality. Accordingly, defects in the regulation of the actin cytoskeleton in neurons have been implicated in memory disorders. Due to the small size of spines, it is difficult to detect changes in the actin structures in dendritic spines by conventional light microscopy imaging. Instead, to know how tightly actin filaments are bundled together, and how fast the filaments turnover, we need to use advanced microscopy techniques, such as fluorescence recovery after photobleaching (FRAP), photoactivatable green fluorescent protein (PAGFP) fluorescence decay and fluorescence anisotropy. Fluorescence anisotropy, which measures the Forster resonance energy transfer (FRET) between two GFP fluorophores, has been proposed as a method to measure the level of actin polymerization. Here, we propose a novel idea that fluorescence anisotropy could be more suitable to study the level of actin filament bundling instead of actin polymerization. We validate the method in U2OS cell line where the actin structures can be clearly distinguished and apply to analyze how actin filament organization in dendritic spines changes during neuronal maturation. In addition to fluorescence anisotropy validation, we take a critical look at the properties and limitations of FRAP and PAGFP fluorescence decay methods and offer our proposals for the analysis methods for these approaches. These three methods complement each other, each providing additional information about actin dynamics and organization in dendritic spines. PMID- 25140132 TI - Retino-hypothalamic regulation of light-induced murine sleep. AB - The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area (VLPO) and the suprachiasmatic nucleus (SCN). We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages. PMID- 25140133 TI - Speech sound discrimination training improves auditory cortex responses in a rat model of autism. AB - Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses. Prenatal exposure to the antiepileptic drug valproic acid (VPA) increases the risk for autism and language impairment. Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses in rats. In this study, we document speech sound discrimination ability in VPA exposed rats and document the effect of extensive speech training on auditory cortex responses. VPA exposed rats were significantly impaired at consonant, but not vowel, discrimination. Extensive speech training resulted in both stronger and faster anterior auditory field (AAF) responses compared to untrained VPA exposed rats, and restored responses to control levels. This neural response improvement generalized to non-trained sounds. The rodent VPA model of autism may be used to improve the understanding of speech processing in autism and contribute to improving language outcomes. PMID- 25140130 TI - Dopamine modulation of learning and memory in the prefrontal cortex: insights from studies in primates, rodents, and birds. AB - In this review, we provide a brief overview over the current knowledge about the role of dopamine transmission in the prefrontal cortex during learning and memory. We discuss work in humans, monkeys, rats, and birds in order to provide a basis for comparison across species that might help identify crucial features and constraints of the dopaminergic system in executive function. Computational models of dopamine function are introduced to provide a framework for such a comparison. We also provide a brief evolutionary perspective showing that the dopaminergic system is highly preserved across mammals. Even birds, following a largely independent evolution of higher cognitive abilities, have evolved a comparable dopaminergic system. Finally, we discuss the unique advantages and challenges of using different animal models for advancing our understanding of dopamine function in the healthy and diseased brain. PMID- 25140134 TI - Brain-machine interfacing control of whole-body humanoid motion. AB - We propose to tackle in this paper the problem of controlling whole-body humanoid robot behavior through non-invasive brain-machine interfacing (BMI), motivated by the perspective of mapping human motor control strategies to human-like mechanical avatar. Our solution is based on the adequate reduction of the controllable dimensionality of a high-DOF humanoid motion in line with the state of-the-art possibilities of non-invasive BMI technologies, leaving the complement subspace part of the motion to be planned and executed by an autonomous humanoid whole-body motion planning and control framework. The results are shown in full physics-based simulation of a 36-degree-of-freedom humanoid motion controlled by a user through EEG-extracted brain signals generated with motor imagery task. PMID- 25140135 TI - Oxytocin increases liking for a country's people and national flag but not for other cultural symbols or consumer products. AB - The neuropeptide oxytocin enhances in-group favoritism and ethnocentrism in males. However, whether such effects also occur in women and extend to national symbols and companies/consumer products is unclear. In a between-subject, double blind placebo controlled experiment we have investigated the effect of intranasal oxytocin on likeability and arousal ratings given by 51 adult Chinese males and females for pictures depicting people or national symbols/consumer products from both strong and weak in-groups (China and Taiwan) and corresponding out-groups (Japan and South Korea). To assess duration of treatment effects subjects were also re-tested after 1 week. Results showed that although oxytocin selectively increased the bias for overall liking for Chinese social stimuli and the national flag, it had no effect on the similar bias toward other Chinese cultural symbols, companies, and consumer products. This enhanced bias was maintained 1 week after treatment. No overall oxytocin effects were found for Taiwanese, Japanese, or South Korean pictures. Our findings show for the first time that oxytocin increases liking for a nation's society and flag in both men and women, but not that for other cultural symbols or companies/consumer products. PMID- 25140136 TI - Tuning and disrupting the brain-modulating the McGurk illusion with electrical stimulation. AB - In the so-called McGurk illusion, when the synchronized presentation of the visual stimulus /ga/ is paired with the auditory stimulus /ba/, people in general hear it as /da/. Multisensory integration processing underlying this illusion seems to occur within the Superior Temporal Sulcus (STS). Herein, we present evidence demonstrating that bilateral cathodal transcranial direct current stimulation (tDCS) of this area can decrease the McGurk illusion-type responses. Additionally, we show that the manipulation of this audio-visual integrated output occurs irrespective of the number of eye-fixations on the mouth of the speaker. Bilateral anodal tDCS of the Parietal Cortex also modulates the illusion, but in the opposite manner, inducing more illusion-type responses. This is the first demonstration of using non-invasive brain stimulation to modulate multisensory speech perception in an illusory context (i.e., both increasing and decreasing illusion-type responses to a verbal audio-visual integration task). These findings provide clear evidence that both the superior temporal and parietal areas contribute to multisensory integration processing related to speech perception. Specifically, STS seems fundamental for the temporal synchronization and integration of auditory and visual inputs. For its part, posterior parietal cortex (PPC) may adjust the arrival of incoming audio and visual information to STS thereby enhancing their interaction in this latter area. PMID- 25140137 TI - Face processing improvements in prosopagnosia: successes and failures over the last 50 years. AB - Clinicians and researchers have widely believed that face processing cannot be improved in prosopagnosia. Though more than a dozen reported studies have attempted to enhance face processing in prosopagnosics over the last 50 years, evidence for effective treatment approaches has only begun to emerge. Here, we review the current literature on spontaneous recovery in acquired prosopagnosia (AP), as well as treatment attempts in acquired and developmental prosopagnosia (DP), differentiating between compensatory and remedial approaches. We find that for AP, rather than remedial methods, strategic compensatory training such as verbalizing distinctive facial features has shown to be the most effective approach (despite limited evidence of generalization). In children with DP, compensatory training has also shown some effectiveness. In adults with DP, two recent larger-scale studies, one using remedial training and another administering oxytocin, have demonstrated group-level improvements and evidence of generalization. These results suggest that DPs, perhaps because of their more intact face processing infrastructure, may benefit more from treatments targeting face processing than APs. PMID- 25140138 TI - Eluding the illusion? Schizophrenia, dopamine and the McGurk effect. AB - Perceptions are inherently probabilistic; and can be potentially manipulated to induce illusory experience by the presentation of ambiguous or improbable evidence under selective (spatio-temporal) constraints. Accordingly, perception of the McGurk effect, by which individuals misperceive specific incongruent visual and auditory vocal cues, rests upon effective probabilistic inference. Here, we report findings from a behavioral investigation of illusory perception and related metacognitive evaluation during audiovisual integration, conducted in individuals with schizophrenia (n = 30) and control subjects (n = 24) matched in terms of age, sex, handedness and parental occupation. Controls additionally performed the task after an oral dose of amisulpride (400 mg). Individuals with schizophrenia were observed to exhibit illusory perception less frequently than controls, despite non-significant differences in perceptual performance during control conditions. Furthermore, older individuals with schizophrenia exhibited reduced rates of illusory perception. Subsequent analysis revealed a robust inverse relationship between illness chronicity and the illusory perception rate in this group. Controls demonstrated non-significant modulation of perception by amisulpride; amisulpride was, however, found to elicit increases in subjective confidence in perceptual performance. Overall, these findings are consistent with the idea that impairments in probabilistic inference are exhibited in schizophrenia and exacerbated by illness chronicity. The latter suggests that associated processes are a potentially worthwhile target for therapeutic intervention. PMID- 25140139 TI - Challenges for identifying the neural mechanisms that support spatial navigation: the impact of spatial scale. AB - Spatial navigation is a fascinating behavior that is essential for our everyday lives. It involves nearly all sensory systems, it requires numerous parallel computations, and it engages multiple memory systems. One of the key problems in this field pertains to the question of reference frames: spatial information such as direction or distance can be coded egocentrically-relative to an observer-or allocentrically-in a reference frame independent of the observer. While many studies have associated striatal and parietal circuits with egocentric coding and entorhinal/hippocampal circuits with allocentric coding, this strict dissociation is not in line with a growing body of experimental data. In this review, we discuss some of the problems that can arise when studying the neural mechanisms that are presumed to support different spatial reference frames. We argue that the scale of space in which a navigation task takes place plays a crucial role in determining the processes that are being recruited. This has important implications, particularly for the inferences that can be made from animal studies in small scale space about the neural mechanisms supporting human spatial navigation in large (environmental) spaces. Furthermore, we argue that many of the commonly used tasks to study spatial navigation and the underlying neuronal mechanisms involve different types of reference frames, which can complicate the interpretation of neurophysiological data. PMID- 25140140 TI - Listening effort and accented speech. PMID- 25140142 TI - Left occipitotemporal cortex contributes to the discrimination of tool-associated hand actions: fMRI and TMS evidence. AB - Functional neuroimaging studies have implicated the left lateral occipitotemporal cortex (LOTC) in both tool and hand perception but the functional role of this region is not fully known. Here, by using a task manipulation, we tested whether tool-/hand-selective LOTC contributes to the discrimination of tool-associated hand actions. Participants viewed briefly presented pictures of kitchen and garage tools while they performed one of two tasks: in the action task, they judged whether the tool is associated with a hand rotation action (e.g., screwdriver) or a hand squeeze action (e.g., garlic press), while in the location task they judged whether the tool is typically found in the kitchen (e.g., garlic press) or in the garage (e.g., screwdriver). Both tasks were performed on the same stimulus set and were matched for difficulty. Contrasting fMRI responses between these tasks showed stronger activity during the action task than the location task in both tool- and hand-selective LOTC regions, which closely overlapped. No differences were found in nearby object- and motion-selective control regions. Importantly, these findings were confirmed by a TMS study, which showed that effective TMS over the tool-/hand-selective LOTC region significantly slowed responses for tool action discriminations relative to tool location discriminations, with no such difference during sham TMS. We conclude that left LOTC contributes to the discrimination of tool-associated hand actions. PMID- 25140141 TI - Cues, context, and long-term memory: the role of the retrosplenial cortex in spatial cognition. AB - Spatial navigation requires memory representations of landmarks and other navigation cues. The retrosplenial cortex (RSC) is anatomically positioned between limbic areas important for memory formation, such as the hippocampus (HPC) and the anterior thalamus, and cortical regions along the dorsal stream known to contribute importantly to long-term spatial representation, such as the posterior parietal cortex. Damage to the RSC severely impairs allocentric representations of the environment, including the ability to derive navigational information from landmarks. The specific deficits seen in tests of human and rodent navigation suggest that the RSC supports allocentric representation by processing the stable features of the environment and the spatial relationships among them. In addition to spatial cognition, the RSC plays a key role in contextual and episodic memory. The RSC also contributes importantly to the acquisition and consolidation of long-term spatial and contextual memory through its interactions with the HPC. Within this framework, the RSC plays a dual role as part of the feedforward network providing sensory and mnemonic input to the HPC and as a target of the hippocampal-dependent systems consolidation of long term memory. PMID- 25140144 TI - The joint Simon effect depends on perceived agency, but not intentionality, of the alternative action. AB - A co-actor's intentionality has been suggested to be a key modulating factor for joint action effects like the joint Simon effect (JSE). However, in previous studies intentionality has often been confounded with agency defined as perceiving the initiator of an action as being the causal source of the action. The aim of the present study was to disentangle the role of agency and intentionality as modulating factors of the JSE. In Experiment 1, participants performed a joint go/nogo Simon task next to a co-actor who either intentionally controlled a response button with own finger movements (agency+/intentionality+) or who passively placed the hand on a response button that moved up and down on its own as triggered by computer signals (agency-/intentionality-). In Experiment 2, we included a condition in which participants believed that the co-actor intentionally controlled the response button with a Brain-Computer Interface (BCI) while placing the response finger clearly besides the response button, so that the causal relationship between agent and action effect was perceptually disrupted (agency-/intentionality+). As a control condition, the response button was computer controlled while the co-actor placed the response finger besides the response button (agency-/intentionality-). Experiment 1 showed that the JSE is present with an intentional co-actor and causality between co-actor and action effect, but absent with an unintentional co-actor and a lack of causality between co-actor and action effect. Experiment 2 showed that the JSE is absent with an intentional co-actor, but no causality between co-actor and action effect. Our findings indicate an important role of the co-actor's agency for the JSE. They also suggest that the attribution of agency has a strong perceptual basis. PMID- 25140143 TI - Effective connectivity among the working memory regions during preparation for and during performance of the n-back task. AB - Recent neuroimaging studies have shown that working memory (WM) task difficulty can be decoded from patterns of brain activation in the WM network during preparation to perform those tasks. The inter-regional connectivity among the WM regions during task preparation has not yet been investigated. We examined this question using the graph modeling methods IMaGES and LOFS, applied to the previously published fMRI data of Manelis and Reder (2013). In that study, subjects performed 1-, 2-, and 3-back tasks. Each block of n-back was preceded by a preparation period and followed by a rest period. The analyses of task-related brain activity identified a network of 18 regions that increased in activation from 1- to 3-back (Increase network) and a network of 17 regions that decreased in activation from 1- to 3-back (Decrease network). The graph analyses revealed two types of connectivity sub-networks within the Increase and Decrease networks: "default" and "preparation-related." The "default" connectivity was present not only during task performance, but also during task preparation and during rest. We propose that this sub-network may serve as a core system that allows one to quickly activate cognitive, perceptual and motor systems in response to the relevant stimuli. The "preparation-related" connectivity was present during task preparation and task performance, but not at rest, and depended on the n-back condition. The role of this sub-network may be to pre-activate a connectivity "road map" in order to establish a top-down and bottom-up regulation of attention prior to performance on WM tasks. PMID- 25140145 TI - The hippocampus is not a geometric module: processing environment geometry during reorientation. AB - The hippocampus has long been known to play a role in allocentric spatial coding, but its specific involvement in reorientation, or the recalibration of a disrupted egocentric spatial representation using allocentric spatial information, has received less attention. Initially, the cognitive literature on reorientation focused on a "geometric module" sensitive to the shape formed by extended surfaces in the environment, and the neuroscience literature followed with proposals that particular MTL regions might be the seat of such a module. However, with behavioral evidence mounting that a modular cognitive architecture is unlikely, recent work has begun to directly address the issue of the neural underpinnings of reorientation. In this review, we describe the reorientation paradigm, initial proposals for the role of the MTL when people reorient, our recent work on the neural bases of reorientation, and finally, how this new information regarding neural mechanism helps to re-interpret and clarify the original behavioral reorientation data. PMID- 25140146 TI - Transcranial stimulation of the developing brain: a plea for extreme caution. PMID- 25140148 TI - Changes in scalp potentials and spatial smoothing effects of inclusion of dura layer in human head models for EEG simulations. AB - The dura layer which covers the brain is less conductive than the CSF (cerebrospinal fluid) and also more conductive than the skull bone. This could significantly influence the flow of volume currents from cortex to the scalp surface which will also change the magnitude and spatial profiles of scalp potentials. This was examined with a 3-D finite element method (FEM) model of an adult subject constructed from 192 segmented axial magnetic resonance (MR) slices with 256*256 pixel resolution. The voxel resolution was 1*1*1 mm. The model included the dura layer. In addition, other major tissues were also identified. The electrical conductivities of various tissues were obtained from the literature. The conductivities of dura and CSF were 0.001 S/m and 0.06 S/m, respectively. The electrical activity of the cortex was represented by 144,000 distributed dipolar sources with orientations normal to the local cortical surface. The dipolar intensity was in the range of 0.0-0.4 mA meter with a uniform random distribution. Scalp potentials were simulated for two head models with an adaptive finite element solver. One model had the dura layer and in the other model, dura layer was replaced with the CSF. Spatial contour plots of potentials on the cortical surface, dural surface and the scalp surface were made. With the inclusion of the dura layer, scalp potentials decrease by about 20%. The contours of gyri and sulci structures were visible in the spatial profiles of the cortical potentials which were smoothed out on the dural surface and were not visible on the scalp surface. These results suggest that dura layer should be included for an accurate modeling of scalp and cortical potentials. PMID- 25140149 TI - Genetic variation modifies risk for neurodegeneration based on biomarker status. AB - BACKGROUND: While a great deal of work has gone into understanding the relationship between Cerebrospinal fluid (CSF) biomarkers, brain atrophy, and disease progression, less work has attempted to investigate how genetic variation modifies these relationships. The goal of this study was two-fold. First, we sought to identify high-risk vs. low-risk individuals based on their CSF tau and Abeta load and characterize these individuals with regard to brain atrophy in an AD-relevant region of interest. Next, we sought to identify genetic variants that modified the relationship between biomarker classification and neurodegeneration. METHODS: Participants were categorized based on established cut-points for biomarker positivity. Mixed model regression was used to quantify longitudinal change in the left inferior lateral ventricle. Interaction analyses between single nucleotide polymorphisms (SNPs) and biomarker group status were performed using a genome wide association study (GWAS) approach. Correction for multiple comparisons was performed using the Bonferroni procedure. RESULTS: One intergenic SNP (rs4866650) and one SNP within the SPTLC1 gene (rs7849530) modified the association between amyloid positivity and neurodegeneration. A transcript variant of WDR11-AS1 gene (rs12261764) modified the association between tau positivity and neurodegeneration. These effects were consistent across the two sub-datasets and explained approximately 3% of variance in ventricular dilation. One additional SNP (rs6887649) modified the association between amyloid positivity and baseline ventricular volume, but was not observed consistently across the sub-datasets. CONCLUSIONS: Genetic variation modifies the association between AD biomarkers and neurodegeneration. Genes that regulate the molecular response in the brain to oxidative stress may be particularly relevant to neural vulnerability to the damaging effects of amyloid-beta. PMID- 25140147 TI - Feature integration and object representations along the dorsal stream visual hierarchy. AB - THE VISUAL SYSTEM IS SPLIT INTO TWO PROCESSING STREAMS: a ventral stream that receives color and form information and a dorsal stream that receives motion information. Each stream processes that information hierarchically, with each stage building upon the previous. In the ventral stream this leads to the formation of object representations that ultimately allow for object recognition regardless of changes in the surrounding environment. In the dorsal stream, this hierarchical processing has classically been thought to lead to the computation of complex motion in three dimensions. However, there is evidence to suggest that there is integration of both dorsal and ventral stream information into motion computation processes, giving rise to intermediate object representations, which facilitate object selection and decision making mechanisms in the dorsal stream. First we review the hierarchical processing of motion along the dorsal stream and the building up of object representations along the ventral stream. Then we discuss recent work on the integration of ventral and dorsal stream features that lead to intermediate object representations in the dorsal stream. Finally we propose a framework describing how and at what stage different features are integrated into dorsal visual stream object representations. Determining the integration of features along the dorsal stream is necessary to understand not only how the dorsal stream builds up an object representation but also which computations are performed on object representations instead of local features. PMID- 25140152 TI - Glutathione levels modulation as a strategy in host-parasite interactions insights for biology of cancer. PMID- 25140150 TI - Structure activity relationship of phenolic acid inhibitors of alpha-synuclein fibril formation and toxicity. AB - The aggregation of alpha-synuclein (alpha-syn) is considered the key pathogenic event in many neurological disorders such as Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy, giving rise to a whole category of neurodegenerative diseases known as synucleinopathies. Although the molecular basis of alpha-syn toxicity has not been precisely elucidated, a great deal of effort has been put into identifying compounds that could inhibit or even reverse the aggregation process. Previous reports indicated that many phenolic compounds are potent inhibitors of alpha-syn aggregation. The aim of the present study was to assess the anti-aggregating effect of gallic acid (GA) (3,4,5 trihydroxybenzoic acid), a benzoic acid derivative that belongs to a group of phenolic compounds known as phenolic acids. By employing an array of biophysical and biochemical techniques and a cell-viability assay, GA was shown not only to inhibit alpha-syn fibrillation and toxicity but also to disaggregate preformed alpha-syn amyloid fibrils. Interestingly, GA was found to bind to soluble, non toxic oligomers with no beta-sheet content, and to stabilize their structure. The binding of GA to the oligomers may represent a potential mechanism of action. Additionally, by using structure activity relationship data obtained from fourteen structurally similar benzoic acid derivatives, it was determined that the inhibition of alpha-syn fibrillation by GA is related to the number of hydroxyl moieties and their position on the phenyl ring. GA may represent the starting point for designing new molecules that could be used for the treatment of PD and related disorders. PMID- 25140151 TI - Age-Dependent Modifications of AMPA Receptor Subunit Expression Levels and Related Cognitive Effects in 3xTg-AD Mice. AB - GluA1, GluA2, GluA3, and GluA4 are the constitutive subunits of amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid receptors (AMPARs), the major mediators of fast excitatory transmission in the mammalian central nervous system. Most AMPARs are Ca(2+)-impermeable because of the presence of the GluA2 subunit. GluA2 mRNA undergoes an editing process that results in a Q-R substitution, a key factor in the regulation of AMPAR Ca(2+)-permeability. AMPARs lacking GluA2 or containing the unedited subunit are permeable to Ca(2+) and Zn(2+). The phenomenon physiologically modulates synaptic plasticity while, in pathologic conditions, leads to increased vulnerability to excitotoxic neuronal death. Given the importance of these subunits, we have therefore evaluated possible associations between changes in expression levels of AMPAR subunits and development of cognitive deficits in 3xTg-AD mice, a widely investigated transgenic mouse model of Alzheimer's disease (AD). With quantitative real-time PCR analysis, we assayed hippocampal mRNA expression levels of GluA1-4 subunits occurring in young [3 months of age (m.o.a.)] and old (12 m.o.a) Tg-AD mice and made comparisons with levels found in age-matched wild type (WT) mice. Efficiency of GluA2 RNA editing was also analyzed. All animals were cognitively tested for learning short- and long-term spatial memory with the Morris Water Maze (MWM) navigation task. 3xTg AD mice showed age-dependent decreases of mRNA levels for all the AMPAR subunits, with the exception of GluA2. Editing remained fully efficient with aging in 3xTg AD and WT mice. A one-to-one correlation analysis between MWM performances and GluA1-4 mRNA expression profiles showed negative correlations between GluA2 levels and MWM performances in young 3xTg-AD mice. On the contrary, positive correlations between GluA2 mRNA and MWM performances were found in young WT mice. Our data suggest that increases of AMPARs that contain GluA1, GluA3, and GluA4 subunits may help in maintaining cognition in pre-symptomatic 3xTg-AD mice. PMID- 25140153 TI - Expression pattern of glycoside hydrolase genes in Lutzomyia longipalpis reveals key enzymes involved in larval digestion. AB - The sand fly Lutzomyia longipalpis is the most important vector of American Visceral Leishmaniasis. Adults are phytophagous (males and females) or blood feeders (females only), and larvae feed on solid detritus. Digestion in sand fly larvae has scarcely been studied, but some glycosidase activities putatively involved in microorganism digestion were already described. Nevertheless, the molecular nature of these enzymes, as the corresponding genes and transcripts, were not explored yet. Catabolism of microbial carbohydrates in insects generally involves beta-1,3-glucanases, chitinases, and digestive lysozymes. In this work, the transcripts of digestive beta-1,3-glucanase and chitinases were identified in the L. longipalpis larvae throughout analysis of sequences and expression patterns of glycoside hydrolases families 16, 18, and 22. The activity of one i type lysozyme was also registered. Interestingly, this lysozyme seems to play a role in immunity, rather than digestion. This is the first attempt to identify the molecular nature of sand fly larval digestive enzymes. PMID- 25140154 TI - S-acylation dependent post-translational cross-talk regulates large conductance calcium- and voltage- activated potassium (BK) channels. AB - Mechanisms that control surface expression and/or activity of large conductance calcium-activated potassium (BK) channels are important determinants of their (patho)physiological function. Indeed, BK channel dysfunction is associated with major human disorders ranging from epilepsy to hypertension and obesity. S acylation (S-palmitoylation) represents a major reversible, post-translational modification controlling the properties and function of many proteins including ion channels. Recent evidence reveals that both pore-forming and regulatory subunits of BK channels are S-acylated and control channel trafficking and regulation by AGC-family protein kinases. The pore-forming alpha-subunit is S acylated at two distinct sites within the N- and C-terminus, each site being regulated by different palmitoyl acyl transferases (zDHHCs) and acyl thioesterases (APTs). S-acylation of the N-terminus controls channel trafficking and surface expression whereas S-acylation of the C-terminal domain determines regulation of channel activity by AGC-family protein kinases. S-acylation of the regulatory beta4-subunit controls ER exit and surface expression of BK channels but does not affect ion channel kinetics at the plasma membrane. Furthermore, a significant number of previously identified BK-channel interacting proteins have been shown, or are predicted to be, S-acylated. Thus, the BK channel multi molecular signaling complex may be dynamically regulated by this fundamental post translational modification and thus S-acylation likely represents an important determinant of BK channel physiology in health and disease. PMID- 25140156 TI - Differences in Aerobic Fitness between Inpatients and Outpatients with Severe Mental Disorders. AB - BACKGROUND: Patients with severe mental disorders have increased mortality, and cardiovascular disease (CVD) accounts for a large part. Physical inactivity and low aerobic fitness have been recognized as significant risk factors for CVD. In this study, we investigated the differences in aerobic fitness and physical activity between in- and outpatients with severe mental disorders. METHOD AND SUBJECTS: Fifty in- and outpatients from a regional psychiatric department were included. The patients filled in a questionnaire on physical activity and completed a clinical examination. An estimation of aerobic fitness was calculated for each patient, using gender, age, waist circumference, resting heart rate, and physical activity level as variables. RESULTS: Inpatients had lower estimated aerobic fitness than outpatients (VO2peak 42 vs. 50 mL kg(-1) min(-1), p < 0.001). Compared to population data matched for age and gender, inpatients had lower aerobic fitness, while outpatients were not different from the population average. CONCLUSION: Inpatients at a psychiatric department had lower estimated aerobic fitness than outpatients, and a lower aerobic fitness compared to the general population. Our findings suggest that inpatients with severe mental disorders should be considered a high risk group for CVD. PMID- 25140157 TI - NR2B Antagonist CP-101,606 Abolishes Pitch-Mediated Deviance Detection in Awake Rats. AB - Schizophrenia patients exhibit a decreased ability to detect change in their auditory environment as measured by auditory event-related potentials (ERP) such as mismatch negativity. This deficit has been linked to abnormal NMDA neurotransmission since, among other observations, non-selective channel blockers of NMDA reliably diminish automatic deviance detection in human subjects as well as in animal models. Recent molecular and functional evidence links NR2B receptor subtype to aberrant NMDA transmission in schizophrenia. However, it is unknown if NR2B receptors participate in pre-attentive deviance detection. We recorded ERP from the vertex of freely behaving rats in response to frequency mismatch protocols. We saw a robust increase in N1 response to deviants compared to standard as well as control stimuli indicating true deviance detection. Moreover, the increased negativity was highly sensitive to deviant probability. Next, we tested the effect of a non-selective NMDA channel blocker (ketamine, 30 mg/kg) and a highly selective NR2B antagonist, CP-101,606 (10 or 30 mg/kg) on deviance detection. Ketamine attenuated deviance mainly by increasing the amplitude of the standard ERP. Amplitude and/or latency of several ERP components were also markedly affected. In contrast, CP-101,606 robustly and dose-dependently inhibited the deviant's N1 amplitude, and as a consequence, completely abolished deviance detection. No other ERPs or components were affected. Thus, we report first evidence that NR2B receptors robustly participate in processes of automatic deviance detection in a rodent model. Lastly, our model demonstrates a path forward to test specific pharmacological hypotheses using translational endpoints relevant to aberrant sensory processing in schizophrenia. PMID- 25140155 TI - Systemic and renal oxidative stress in the pathogenesis of hypertension: modulation of long-term control of arterial blood pressure by resveratrol. AB - Hypertension affects over 25% of the global population and is associated with grave and often fatal complications that affect many organ systems. Although great advancements have been made in the clinical assessment and treatment of hypertension, the cause of hypertension in over 90% of these patients is unknown, which hampers the development of targeted and more effective treatment. The etiology of hypertension involves multiple pathological processes and organ systems, however one unifying feature of all of these contributing factors is oxidative stress. Once the body's natural anti-oxidant defense mechanisms are overwhelmed, reactive oxygen species (ROS) begin to accumulate in the tissues. ROS play important roles in normal regulation of many physiological processes, however in excess they are detrimental and cause widespread cell and tissue damage as well as derangements in many physiological processes. Thus, control of oxidative stress has become an attractive target for pharmacotherapy to prevent and manage hypertension. Resveratrol (trans-3,5,4'-Trihydroxystilbene) is a naturally occurring polyphenol which has anti-oxidant effects in vivo. Many studies have shown anti-hypertensive effects of resveratrol in different pre clinical models of hypertension, via a multitude of mechanisms that include its function as an anti-oxidant. However, results have been mixed and in some cases resveratrol has no effect on blood pressure. This may be due to the heavy emphasis on peripheral vasodilator effects of resveratrol and virtually no investigation of its potential renal effects. This is particularly troubling in the arena of hypertension, where it is well known and accepted that the kidney plays an essential role in the long term regulation of arterial pressure and a vital role in the initiation, development and maintenance of chronic hypertension. It is thus the focus of this review to discuss the potential of resveratrol as an anti-hypertensive treatment via amelioration of oxidative stress within the framework of the fundamental physiological principles of long term regulation of arterial blood pressure. PMID- 25140158 TI - Network based statistical analysis detects changes induced by continuous theta burst stimulation on brain activity at rest. AB - We combined continuous theta-burst stimulation (cTBS) and resting state (RS)-fMRI approaches to investigate changes in functional connectivity (FC) induced by right dorsolateral prefrontal cortex (DLPFC)-cTBS at rest in a group of healthy subjects. Seed-based fMRI analysis revealed a specific pattern of correlation between the right prefrontal cortex and several brain regions: based on these results, we defined a 29-node network to assess changes in each network connection before and after, respectively, DLPFC-cTBS and sham sessions. A decrease of correlation between the right prefrontal cortex and right parietal cortex (Brodmann areas 46 and 40, respectively) was detected after cTBS, while no significant result was found when analyzing sham-session data. To our knowledge, this is the first study that demonstrates within-subject changes in FC induced by cTBS applied on prefrontal area. The possibility to induce selective changes in a specific region without interfering with functionally correlated area could have several implications for the study of functional properties of the brain, and for the emerging therapeutic strategies based on transcranial stimulation. PMID- 25140160 TI - Visual relations children find easy and difficult to process in figural analogies. AB - Analogical reasoning, the ability to learn about novel phenomena by relating it to structurally similar knowledge, develops with great variability in children. Furthermore, the development of analogical reasoning coincides with greater working memory efficiency and increasing knowledge of the entities and relations present in analogy problems. In figural matrices, a classical form of analogical reasoning assessment, some features, such as color, appear easier for children to encode and infer than others, such as orientation. Yet, few studies have structurally examined differences in the difficulty of visual relations across different age-groups. This cross-sectional study of figural analogical reasoning examined which underlying rules in figural analogies were easier or more difficult for children to correctly process. School children (N = 1422, M = 7.0 years, SD = 21 months, range 4.5-12.5 years) were assessed in analogical reasoning using classical figural matrices and memory measures. The visual relations the children had to induce and apply concerned the features: animal, color, orientation, position, quantity and size. The role of age and memory span on the children's ability to correctly process each type of relation was examined using explanatory item response theory models. The results showed that with increasing age and/or greater memory span all visual relations were processed more accurately. The "what" visual relations animal, color, quantity and size were easiest, whereas the "where" relations orientation and position were most difficult. However, the "where" visual relations became relatively easier with age and increased memory efficiency. The implications are discussed in terms of the development of visual processing in object recognition vs. position and motion encoding in the ventral ("what") and dorsal ("where") pathways respectively. PMID- 25140159 TI - The biological function of consciousness. AB - This research is an investigation of whether consciousness-one's ongoing experience-influences one's behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1) contrary to one's intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2) consciousness does have a biological function; and (3) consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM) for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate that consciousness is the input data to the FRM. Qualitative and quantitative information (shape, size, location, etc.) are incorporated into the input data by a qualia array of colors, sounds, and so on, which makes the input conscious. This view of the biological function of consciousness provides an explanation why we have experiences; why we have emotional and other feelings, and why their loss is associated with poor decision making; why blindsight patients do not spontaneously initiate responses to events in their blind field; why counter-habitual actions are only possible when the intended action is in mind; and the reason for inattentional blindness. PMID- 25140161 TI - Phonological and lexical influences on phonological awareness in children with specific language impairment and dyslexia. AB - Children with dyslexia and/or specific language impairment have marked deficits in phonological processing, putting them at an increased risk for reading deficits. The current study sought to examine the influence of word-level phonological and lexical characteristics on phonological awareness. Children with dyslexia and/or specific language impairment were tested using a phoneme deletion task in which stimuli differed orthogonally by sound similarity and neighborhood density. Phonological and lexical factors influenced performance differently across groups. Children with dyslexia appeared to have a more immature and aberrant pattern of phonological and lexical influence (e.g., favoring sparse and similar features). Children with SLI performed less well than children who were typically developing, but followed a similar pattern of performance (e.g., favoring dense and dissimilar features). Collectively, our results point to both quantitative and qualitative differences in lexical organization and phonological representations in children with SLI and in children with dyslexia. PMID- 25140162 TI - Distortion of auditory space during visually induced self-motion in depth. AB - Perception of self-motion is based on the integration of multiple sensory inputs, in particular from the vestibular and visual systems. Our previous study demonstrated that vestibular linear acceleration information distorted auditory space perception (Teramoto et al., 2012). However, it is unclear whether this phenomenon is contingent on vestibular signals or whether it can be caused by inputs from other sensory modalities involved in self-motion perception. Here, we investigated whether visual linear self-motion information can also alter auditory space perception. Large-field visual motion was presented to induce self motion perception with constant accelerations (Experiment 1) and a constant velocity (Experiment 2) either in a forward or backward direction. During participants' experience of self-motion, a short noise burst was delivered from one of the loudspeakers aligned parallel to the motion direction along a wall to the left of the listener. Participants indicated from which direction the sound was presented, forward or backward, relative to their coronal (i.e., frontal) plane. Results showed that the sound position aligned with the subjective coronal plane (SCP) was significantly displaced in the direction of self-motion, especially in the backward self-motion condition as compared with a no motion condition. These results suggest that self-motion information, irrespective of its origin, is crucial for auditory space perception. PMID- 25140163 TI - The role of ANS acuity and numeracy for the calibration and the coherence of subjective probability judgments. AB - The purpose of the study was to investigate how numeracy and acuity of the approximate number system (ANS) relate to the calibration and coherence of probability judgments. Based on the literature on number cognition, a first hypothesis was that those with lower numeracy would maintain a less linear use of the probability scale, contributing to overconfidence and nonlinear calibration curves. A second hypothesis was that also poorer acuity of the ANS would be associated with overconfidence and non-linearity. A third hypothesis, in line with dual-systems theory (e.g., Kahneman and Frederick, 2002) was that people higher in numeracy should have better access to the normative probability rules, allowing them to decrease the rate of conjunction fallacies. Data from 213 participants sampled from the Swedish population showed that: (i) in line with the first hypothesis, overconfidence and the linearity of the calibration curves were related to numeracy, where people higher in numeracy were well calibrated with zero overconfidence. (ii) ANS was not associated with overconfidence and non linearity, disconfirming the second hypothesis. (iii) The rate of conjunction fallacies was slightly, but to a statistically significant degree decreased by numeracy, but still high at all numeracy levels. An unexpected finding was that participants with better ANS acuity gave more realistic estimates of their performance relative to others. PMID- 25140164 TI - Use of the adult attachment projective picture system in psychodynamic psychotherapy with a severely traumatized patient. AB - The following case study is presented to facilitate an understanding of how the attachment information evident from Adult Attachment Projective Picture System (AAP) assessment can be integrated into a psychodynamic perspective in making therapeutic recommendations that integrate an attachment perspective. The Adult Attachment Projective Picture System (AAP) is a valid representational measure of internal representations of attachment based on the analysis of a set of free response picture stimuli designed to systematically activate the attachment system (George and West, 2012). The AAP provides a fruitful diagnostic tool for psychodynamic-oriented clinicians to identify attachment-based deficits and resources for an individual patient in therapy. This paper considers the use of the AAP with a traumatized patient in an inpatient setting and uses a case study to illustrate the components of the AAP that are particularly relevant to a psychodynamic conceptualization. The paper discusses also attachment-based recommendations for intervention. PMID- 25140165 TI - Pharmacological Treatments Inhibiting Levodopa-Induced Dyskinesias in MPTP Lesioned Monkeys: Brain Glutamate Biochemical Correlates. AB - Anti-glutamatergic drugs can relieve Parkinson's disease (PD) symptoms and decrease l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesias (LID). This review reports relevant studies investigating glutamate receptor subtypes in relation to motor complications in PD patients and 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-lesioned monkeys. Antagonists of the ionotropic glutamate receptors, such as N-methyl-d-aspartate (NMDA) and alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, display antidyskinetic activity in PD patients and animal models such as the MPTP monkey. Metabotropic glutamate 5 (mGlu5) receptor antagonists were shown to reduce the severity of LID in PD patients as well as in already dyskinetic non-human primates and to prevent the development of LID in de novo treatments in non-human primates. An increase in striatal post-synaptic NMDA, AMPA, and mGlu5 receptors is documented in PD patients and MPTP monkeys with LID. This increase can be prevented in MPTP monkeys with the addition of a specific glutamate receptor antagonist to the l-DOPA treatment and also with drugs of various pharmacological specificities suggesting multiple receptor interactions. This is yet to be well documented for presynaptic mGlu4 and mGlu2/3 and offers additional new promising avenues. PMID- 25140167 TI - Grappling archaea: ultrastructural analyses of an uncultivated, cold-loving archaeon, and its biofilm. AB - Similarly to Bacteria, Archaea are microorganisms that interact with their surrounding environment in a versatile manner. To date, interactions based on cellular structure and surface appendages have mainly been documented using model systems of cultivable archaea under laboratory conditions. Here, we report on the microbial interactions and ultrastructural features of the uncultivated SM1 Euryarchaeon, which is highly dominant in its biotope. Therefore, biofilm samples taken from the Sippenauer Moor, Germany, were investigated via transmission electron microscopy (TEM; negative staining, thin-sectioning) and scanning electron microscopy (SEM) in order to elucidate the fine structures of the microbial cells and the biofilm itself. The biofilm consisted of small archaeal cocci (0.6 MUm diameter), arranged in a regular pattern (1.0-2.0 MUm distance from cell to cell), whereas each archaeon was connected to 6 other archaea on average. Extracellular polymeric substances (EPS) were limited to the close vicinity of the archaeal cells, and specific cell surface appendages (hami, Moissl et al., 2005) protruded beyond the EPS matrix enabling microbial interaction by cell-cell contacts among the archaea and between archaea and bacteria. All analyzed hami revealed their previously described architecture of nano-grappling hooks and barb-wire basal structures. Considering the archaeal cell walls, the SM1 Euryarchaea exhibited a double-membrane, which has rarely been reported for members of this phylogenetic domain. Based on these findings, the current generalized picture on archaeal cell walls needs to be revisited, as archaeal cell structures are more complex and sophisticated than previously assumed, particularly when looking into the uncultivated majority. PMID- 25140168 TI - Halophilic Aspergillus penicillioides from athalassohaline, thalassohaline, and polyhaline environments. AB - Aspergillus penicillioides is a true halophile, present in diverse econiches - from the hypersaline athalassohaline, and thalassohaline environments, to polyhaline systems, and in different geographical locations. Twenty seven isolates from these environments, were seen to be moderate halophiles, euryhaline in nature. They had an obligate need of a low aw and were unable to grow on a regular defined medium such as Czapek Dox Agar, as well as on varied nutrient rich agar media such as Malt Extract, Potato Dextrose and Sabouraud Agar; however, growth was obtained on all these media when amended with 10% solar salt. In absence of added salt, the conidia either did not germinate, or when germinated, distortions and lysis were seen in the short mycelial forms; on media with salt, the mycelia and vesicles appeared normal. PMID- 25140166 TI - ER stress, autophagy, and RNA viruses. AB - Endoplasmic reticulum (ER) stress is a general term for representing the pathway by which various stimuli affect ER functions. ER stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (UPR), which compromises the stimulus and then determines whether the cell survives or dies. In recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell's response to various stressors. Autophagy performs a self-digestion function, and its activation protects cells against certain pathogens. However, the link between the UPR and autophagy may be more complicated. These two systems may act dependently, or the induction of one system may interfere with the other. Experimental studies have found that different viruses modulate these mechanisms to allow them to escape the host immune response or, worse, to exploit the host's defense to their advantage; thus, this topic is a critical area in antiviral research. In this review, we summarize the current knowledge about how RNA viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71, Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these processes. We also discuss recent discoveries and how these will produce novel strategies for antiviral treatment. PMID- 25140169 TI - A Question of Nature: Some Antigens are Bound to be Allergens. PMID- 25140171 TI - Structural divergence and loss of phosphoinositide-specific phospholipase C signaling components during the evolution of the green plant lineage: implications from structural characteristics of algal components. PMID- 25140172 TI - Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement. AB - Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID- 25140170 TI - Maize transformation technology development for commercial event generation. AB - Maize is an important food and feed crop in many countries. It is also one of the most important target crops for the application of biotechnology. Currently, there are more biotech traits available on the market in maize than in any other crop. Generation of transgenic events is a crucial step in the development of biotech traits. For commercial applications, a high throughput transformation system producing a large number of high quality events in an elite genetic background is highly desirable. There has been tremendous progress in Agrobacterium-mediated maize transformation since the publication of the Ishida et al. (1996) paper and the technology has been widely adopted for transgenic event production by many labs around the world. We will review general efforts in establishing efficient maize transformation technologies useful for transgenic event production in trait research and development. The review will also discuss transformation systems used for generating commercial maize trait events currently on the market. As the number of traits is increasing steadily and two or more modes of action are used to control key pests, new tools are needed to efficiently transform vectors containing multiple trait genes. We will review general guidelines for assembling binary vectors for commercial transformation. Approaches to increase transformation efficiency and gene expression of large gene stack vectors will be discussed. Finally, recent studies of targeted genome modification and transgene insertion using different site-directed nuclease technologies will be reviewed. PMID- 25140173 TI - Hypothesis: genetic and epigenetic risk factors interact to modulate vulnerability and resilience to FASD. AB - Fetal alcohol spectrum disorder (FASD) presents a collection of symptoms representing physiological and behavioral phenotypes caused by maternal alcohol consumption. Symptom severity is modified by genetic differences in fetal susceptibility and resistance as well as maternal genetic factors such as maternal alcohol sensitivity. Animal models demonstrate that both maternal and paternal genetics contribute to the variation in the fetus' vulnerability to alcohol exposure. Maternal and paternal genetics define the variations in these phenotypes even without the effect of alcohol in utero, as most of these traits are polygenic, non-Mendelian, in their inheritance. In addition, the epigenetic alterations that instigate the alcohol induced neurodevelopmental deficits can interact with the polygenic inheritance of respective traits. Here, based on specific examples, we present the hypothesis that the principles of non-Mendelian inheritance, or "exceptions" to Mendelian genetics, can be the driving force behind the severity of the prenatal alcohol-exposed individual's symptomology. One such exception is when maternal alleles lead to an altered intrauterine hormonal environment and, therefore, produce variations in the long-term consequences on the development of the alcohol-exposed fetus. Another exception is when epigenetic regulation of allele-specific gene expression generates disequilibrium between the maternal vs. paternal genetic contributions, and thereby, modifies the effect of prenatal alcohol exposure on the fetus. We propose that these situations in which one parent has an exaggerated influence over the offspring's vulnerability to prenatal alcohol are major contributing mechanisms responsible for the variations in the symptomology of FASD in the exposed generation and beyond. PMID- 25140174 TI - Thalassophryne nattereri fish venom: from the envenoming to the understanding of the immune system. AB - Thalassophryne nattereri (niquim) is a venomous fish found off North and Northeast coast of Brazil, where it is known by the severity of the accidents involving humans. This review article is divided into four topics. The first one provides a brief description of the animal biology and its distribution off Brazilian coastal waters, the venom apparatus, signs and symptoms observed in envenomated humans and also describes envenomation in mice. The second topic describes the use of modern genetic approach and mass spectrometry for identification of highly expressed genes in its venom glands and the sequence of major toxins. The third chapter offers a detailed study of tissue injury induced by the venom and reveals the role of toxins that impair inflammation reduction. Finally, the fourth section expands the understanding of many extrinsic and intrinsic essential factors in maintaining survival of memory B cell compartment. Our results demonstrate the wide possibilities for research in the area of toxinology, also the necessity of interconnection among biochemistry, pharmacology and immunology areas for the expansion of knowledge and for generation of innovation. PMID- 25140175 TI - Multidrug resistance: an emerging crisis. AB - The resistance among various microbial species (infectious agents) to different antimicrobial drugs has emerged as a cause of public health threat all over the world at a terrifying rate. Due to the pacing advent of new resistance mechanisms and decrease in efficiency of treating common infectious diseases, it results in failure of microbial response to standard treatment, leading to prolonged illness, higher expenditures for health care, and an immense risk of death. Almost all the capable infecting agents (e.g., bacteria, fungi, virus, and parasite) have employed high levels of multidrug resistance (MDR) with enhanced morbidity and mortality; thus, they are referred to as "super bugs." Although the development of MDR is a natural phenomenon, the inappropriate use of antimicrobial drugs, inadequate sanitary conditions, inappropriate food-handling, and poor infection prevention and control practices contribute to emergence of and encourage the further spread of MDR. Considering the significance of MDR, this paper, emphasizes the problems associated with MDR and the need to understand its significance and mechanisms to combat microbial infections. PMID- 25140177 TI - Increased incidence of thyroid dysfunction and autoimmunity in patients with vernal keratoconjunctivitis. AB - Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis (VKC). An increased incidence of thyroid autoantibodies was recently observed in VKC, although there were no data on thyroid function. Two hundred and eighty eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were evaluated and compared with 188 normal age- and sex-matched subjects. In all subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin, and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid diseases showed no significant differences compared to the controls (9.4 versus 8.6%), whereas the family history of autoimmune diseases was significantly higher (13.2% versus 6.3%; P<0.05). Subclinical hypothyroidism was diagnosed in 6.6% (versus 1.6% of the controls; P<0.05) and overt hypothyroidism in 0.7% (versus 0.0% of the controls; P = NS). Finally, 5.2% of patients were positive for thyroid autoantibodies, which were significantly higher with respect to the controls (0.5%, P<0.05). In the patients positive for thyroid autoantibodies, 80% showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid function and autoimmunity abnormalities are frequently present in children with VKC. Children with VKC should be screened for thyroid function and evaluated for thyroid autoimmunity. PMID- 25140178 TI - Concomitant factors leading to an atypical osteonecrosis of the jaw in a patient with multiple myeloma. AB - Osteonecrosis of the jaw (ONJ) is a site specific osseous pathology, characterized by chronic exposed bone in the mouth, which needs to be reinforced periodically within the medical literature. ONJ is a clinical entity with many possible aetiologies and its pathogenesis is not well understood. The risk factors for ONJ include bisphosphonates treatments, head and neck radiotherapy, dental procedures involving bone surgery, and trauma. Management of ONJ has centred on efforts to eliminate or reduce severity of symptoms, to slow or prevent the progression of disease, and to eradicate diseased bone. This case describes a rare case of ONJ in a 64-year-old Caucasian male diagnosed with multiple myeloma stage III. The lesion was related to a traumatic injury during mastication. Eighteen months ago in the same area the molar 37 was extracted, achieving a complete satisfactory healing, when only 2 doses of zoledronic acid had been administered. Actinomyces bacterial aggregates were also identified in the microscopic analysis. The management of this osteonecrotic lesion included antibiotic treatment and chlorhexidine topical gel administration. The evolution was monitored every two weeks until patient's death. The authors provide a discussion of the etiology, pathogenesis, diagnosis, and management. This case report may shed light on the controversies about concomitant factors and mechanisms inducing ONJ. PMID- 25140179 TI - Laryngeal lymphoma: the high and low grades of rare lymphoma involvement sites. AB - The larynx is an extremely rare site of involvement by lymphomatous disease. We present two cases of isolated laryngeal high-grade and another low-grade lymphoma, together with a literature review of laryngeal lymphoma management. PMID- 25140180 TI - Acute zonal occult outer retinopathy with atypical findings. AB - Background. To report a case of acute zonal occult outer retinopathy (AZOOR) with atypical electrophysiology findings. Case Presentation. A 23-year-old-female presented with visual acuity deterioration in her right eye accompanied by photopsia bilaterally. Corrected distance visual acuity at presentation was 20/50 in the right eye and 20/20 in the left eye. Fundus examination was unremarkable. Visual field (VF) testing revealed a large scotoma. Pattern and full-field electroretinograms (PERG and ERG) revealed macular involvement associated with generalized retinal dysfunction. Electrooculogram (EOG) light rise and the Arden ratio were within normal limits bilaterally. The patient was diagnosed with AZOOR due to clinical findings, visual field defect, and ERG findings. Conclusion. This is a case of AZOOR with characteristic VF defects and clinical symptoms presenting with atypical EOG findings. PMID- 25140181 TI - Acute rhabdomyolysis associated with coadministration of levofloxacin and simvastatin in a patient with normal renal function. AB - We report a rare case of severe acute rhabdomyolysis in association with coadministration of levofloxacin and simvastatin in a patient with normal renal function. A 70-year-old Caucasian male was treated due to community acquired pneumonia with levofloxacin in a dosage of 500 mg once and then twice a day. On the 8th day of hospitalization the patient presented with acute severe rhabdomyolysis requiring an intensive care support. After discontinuation of levofloxacin and concomitant medication with simvastatin 80 mg/day, clinical and laboratory effects were totally reversible. Up to now, levofloxacin has been reported to induce rhabdomyolysis mainly in patients with impaired renal function, as the medication has a predominant renal elimination. In our case renal function remained normal during the severe clinical course. According to a recent case report rhabdomyolysis was observed due to interaction of simvastatin and ciprofloxacin. To our best knowledge this is the first case of interaction between simvastatin and levofloxacin to be reported. This case emphasizes the need of close monitoring of creatine kinase in patients under more than one potentially myotoxic medication especially when patients develop muscle weakness. PMID- 25140182 TI - Bilateral Upper Extremity DVT in a 43-Year-Old Man: Is It Thoracic Outlet Syndrome?! AB - Recurrent deep venous thrombosis, involving bilateral upper extremities, is an extremely rare phenomenon. We are presenting a 43-year-old man who was diagnosed with left upper extremity deep vein thrombosis (UEDVT) and was treated with anticoagulation and surgical decompression in 2004. 9 years later, he presented with right arm swelling and was diagnosed with right UEDVT using US venous Doppler. Venogram showed compression of the subclavian vein by the first rib, diagnosing thoracic outlet syndrome (TOS). He was treated with anticoagulation and local venolysis and later by surgical decompression of the subclavian vein. Bilateral UEDVT, as mentioned above, is an extremely rare condition that is uncommonly caused by TOS. To our knowledge, we are reporting the first case of bilateral UEDVT due to TOS. Diagnosis usually starts with US venous Doppler to detect the thrombosis, followed by the gold standard venogram to locate the area of obstruction and lyse the thrombus if needed. The ultimate treatment for TOS remains surgical decompression of the vascular bundle at the thoracic outlet. PMID- 25140183 TI - Challenges and frugal remedies for lowering facility based neonatal mortality and morbidity: a comparative study. AB - Millennium development goal target on infant mortality (MDG4) by 2015 would not be realised in some low-resource countries. This was in part due to unsustainable high-tech ideas that have been poorly executed. Prudent but high impact techniques could have been synthesised in these countries. A collaborative outreach was initiated to devise frugal measures that could reduce neonatal deaths in Nigeria. Prevailing issues of concern that could militate against neonatal survival within care centres were identified and remedies were proffered. These included application of (i) recycled incubator technology (RIT) as a measure of providing affordable incubator sufficiency, (ii) facility-based research groups, (iii) elective training courses for clinicians/nurses, (iv) independent local artisans on spare parts production, (v) power-banking and apnoea-monitoring schemes, and (v) 1/2 yearly failure-preventive maintenance and auditing system. Through a retrospective data analyses 4 outreach centres and one "control" were assessed. Average neonatal mortality of centres reduced from 254/1000 to 114/1000 whilst control remained at 250/1000. There was higher relative influx of incubator-dependent-neonates at outreach centres. It was found that 43% of mortality occurred within 48 hours of presentation (d48) and up to 92% of d48 were of very-low birth parameters. The RIT and associated concerns remedies have demonstrated the vital signs of efficiency that would have guaranteed MDG4 neonatal component in Nigeria. PMID- 25140184 TI - Neuroprotective effects of cuscutae semen in a mouse model of Parkinson's disease. AB - Parkinson's disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. 1 Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage to the DA neurons, and 1-4-methyl-4-phenylpyridinium (MPP(+)) causes cell death in differentiated PC12 cells that is similar to the degeneration that occurs in PD. Moreover, MPTP treatment increases the activity of the brain's immune cells, reactive oxygen species- (ROS-) generating processes, and glutathione peroxidase. We recently reported that Cuscutae Semen (CS), a widely used traditional herbal medicine, increases cell viability in a yeast model of PD. In the present study, we examined the inhibitory effect of CS on the neurotoxicity of MPTP in mice and on the MPP+-induced cell death in differentiated PC12 cells. The MPTP-induced loss of nigral DA neurons was partly inhibited by CS-mediated decreases in ROS generation. The activation of microglia was slightly inhibited by CS, although this effect did not reach statistical significance. Furthermore, CS may reduce the MPP+ toxicity in PC12 cells by suppressing glutathione peroxidase activation. These results suggest that CS may be beneficial for the treatment of neurodegenerative diseases such as PD. PMID- 25140176 TI - The alliance of mesenchymal stem cells, bone, and diabetes. AB - Bone fragility has emerged as a new complication of diabetes. Several mechanisms in diabetes may influence bone homeostasis by impairing the action between osteoblasts, osteoclasts, and osteocytes and/or changing the structural properties of the bone tissue. Some of these mechanisms can potentially alter the fate of mesenchymal stem cells, the initial precursor of the osteoblast. In this review, we describe the main factors that impair bone health in diabetic patients and their clinical impact. PMID- 25140186 TI - Moxibustion Activates Macrophage Autophagy and Protects Experimental Mice against Bacterial Infection. AB - Moxibustion is one of main therapies in traditional Chinese medicine and uses heat stimulation on the body surface from the burning of moxa to release pain or treat diseases. Emerging studies have shown that moxibustion can generate therapeutic effects by activating a series of signaling pathways and neuroendocrine-immune activities. Here we show moxibustion promoted profound macrophage autophagy in experimental Kunming mice, with reduced Akt phosphorylation and activated eIF2alpha phosphorylation. Consequently, moxibustion promoted bacterial clearance by macrophages and protected mice from mortality due to bacterial infection. These results indicate that moxibustion generates a protective response by activating autophagy against bacterial infections. PMID- 25140185 TI - A Metabonomics Profiling Study on Phlegm Syndrome and Blood-Stasis Syndrome in Coronary Heart Disease Patients Using Liquid Chromatography/Quadrupole Time-of Flight Mass Spectrometry. AB - A metabonomics approach based on liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) was utilized to obtain potential biomarkers of coronary heart disease (CHD) patients and investigate the ZHENG types differentiation in CHD patients. The plasma samples of 20 CHD patients with phlegm syndrome, 20 CHD patients with blood-stasis syndrome, and 16 healthy volunteers were collected in the study. 26 potential biomarkers were identified in the plasma of CHD patients and 19 differential metabolites contributed to the discrimination of phlegm syndrome and blood-stasis syndrome in CHD patients (VIP > 1.5; P < 0.05) which mainly involved purine metabolism, pyrimidine metabolism, amino acid metabolism, steroid biosynthesis, and arachidonic acid metabolism. This study demonstrated that metabonomics approach based on LC-MS was useful for studying pathologic changes of CHD patients and interpreting the differentiation of ZHENG types (phlegm and blood-stasis syndrome) in traditional Chinese medicine (TCM). PMID- 25140187 TI - Chemical Profiling of an Antimigraine Herbal Preparation, Tianshu Capsule, Based on the Combination of HPLC, LC-DAD-MS (n) , and LC-DAD-ESI-IT-TOF/MS Analyses. AB - Chemical profiling is always the first task in the standardization and modernization of Traditional Chinese Medicine. HPLC and LC-MS were employed to find out the common chromatographic peaks in various batches of Tianshu Capsule (TSC) and the contribution of the characteristic peaks from individual herbs to the whole chromatographic profile of TSC sample. A total of 38 constituents were identified in TSC sample based on the comparison of retention time and UV spectra with authentic compounds as well as by summarized MS fragmentation rules and matching of empirical molecular formula with those of published components. This is the first systematic report on the chemical profiling of the commercial TSC product, which provides the sufficiently chemical evidence for the global quality evaluation of TSC products. PMID- 25140188 TI - Investigation of hepatic blood perfusion by laser speckle imaging and changes of hepatic vasoactive substances in mice after electroacupuncture. AB - The study was conducted to observe the effect of electroacupuncture (EA) on hepatic blood perfusion (HBP) and vascular regulation. We investigated 60 male anesthetized mice under the following 3 conditions: without EA stimulation (control group); EA stimulation at Zusanli (ST36 group); EA stimulation at nonacupoint (NA group) during 30 min. The HBP was measured using the laser speckle perfusion imaging (LSPI). The level of nitric oxide (NO), endothelin-1 (ET-1), and noradrenaline (NE) in liver tissue was detected by biochemical methods. Results were as follows. At each time point, HBP increase in ST36 group was higher than that in the NA group in anesthetized mice. HBP gradually decreased during 30 min in control group. The level of NO in ST36 group was higher than that in NA group. The level of both ET-1 and NE was the highest in control group, followed by NA group and ST36 group. It is concluded that EA at ST36 could increase HBP possibly by increasing the blood flow velocity (BFV), changing vascular activity, increasing the level of NO, and inhibiting the level of ET-1 in liver tissue. PMID- 25140189 TI - Caffeamide 36-13 Regulates the Antidiabetic and Hypolipidemic Signs of High-Fat Fed Mice on Glucose Transporter 4, AMPK Phosphorylation, and Regulated Hepatic Glucose Production. AB - This study was to investigate the antidiabetic and antihyperlipidemic effects of (E)-3-[3, 4-dihydroxyphenyl-1-(piperidin-1-yl)prop-2-en-1-one] (36-13) (TS), one of caffeic acid amide derivatives, on high-fat (HF-) fed mice. The C57BL/6J mice were randomly divided into the control (CON) group and the experimental group, which was firstly fed a HF diet for 8 weeks. Then, the HF group was subdivided into four groups and was given TS orally (including two doses) or rosiglitazone (Rosi) or vehicle for 4 weeks. Blood, skeletal muscle, and tissues were examined by measuring glycaemia and dyslipidemia-associated events. TS effectively prevented HF diet-induced increases in the levels of blood glucose, triglyceride, insulin, leptin, and free fatty acid (FFA) and weights of visceral fa; moreover, adipocytes in the visceral depots showed a reduction in size. TS treatment significantly increased the protein contents of glucose transporter 4 (GLUT4) in skeletal muscle; TS also significantly enhanced Akt phosphorylation in liver, whereas it reduced the expressions of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Moreover, TS enhanced phosphorylation of AMP activated protein kinase (phospho-AMPK) both in skeletal muscle and liver tissue. Therefore, it is possible that the activation of AMPK by TS resulted in enhanced glucose uptake in skeletal muscle, contrasting with diminished gluconeogenesis in liver. TS exhibits hypolipidemic effect by decreasing the expressions of fatty acid synthase (FAS). Thus, antidiabetic properties of TS occurred as a result of decreased hepatic glucose production by PEPCK and G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic state by TS in HF-fed mice occurred by regulation of GLUT4, G6Pase, and FAS and phosphorylation of AMPK. PMID- 25140190 TI - Pharmacokinetics and tissue distribution study of chlorogenic Acid from lonicerae japonicae flos following oral administrations in rats. AB - Chlorogenic acid (ChA) is proposed as the major bioactive compounds of Lonicerae Japonicae Flos (LJF). Forty-two Wistar rats were randomly divided into seven groups to investigate the pharmacokinetics and tissue distribution of ChA, via oral administration of LJF extract, using ibuprofen as internal standard, employing a high performance liquid chromatography in conjunction with tandem mass spectrometry. Analytes were extracted from plasma samples and tissue homogenate by liquid-liquid extraction with acetonitrile, separated on a C 18 column by linear gradient elution, and detected by electrospray ionization mass spectrometry in negative selected multiple reaction monitoring mode. Our results successfully demonstrate that the method has satisfactory selectivity, linearity, extraction recovery, matrix effect, precision, accuracy, and stability. Using noncompartment model to study pharmacokinetics, profile revealed that ChA was rapidly absorbed and eliminated. Tissue study indicated that the highest level was observed in liver, followed by kidney, lung, heart, and spleen. In conclusion, this method was suitable for the study on pharmacokinetics and tissue distribution of ChA after oral administration. PMID- 25140191 TI - Effects and mechanisms of resveratrol on the amelioration of oxidative stress and hepatic steatosis in KKAy mice. AB - BACKGROUND: The exact mechanism of the protective role of Resveratrol (Res) in lipid metabolism and oxidative stress is not well elucidated. The present study aimed to investigate the potential benefits and possible mechanisms of Res on the amelioration of oxidative stress and hepatic steatosis in a KKAy mouse model. METHODS: A total of 30 KKAy male mice were randomly divided into three groups: a normal chow group, a low resveratrol group and a high resveratrol group. After a 12-wk study period, serum levels of TG, TC, LDL-C and HDL-C, the liver content of TG and TC, ROS, GSH, GPx, SOD and MDA levels were measured. Ectopic lipid deposition was observed in sectioned frozen liver tissues. The mRNA levels of ATGL and HSL in the liver tissues were determined via real-time PCR. Furthermore, the protein expression of p47phox, gp91phox, ATGL, HSL, Sirt1, AMPK and FOXO1 were analyzed using western blotting. RESULTS: Following Res supplementation, serum levels of TG and MDA were decreased, while the HDL-C and SOD levels were increased in KKAy mice. Furthermore, Res treatment increased GSH and GPx in liver tissues, while it decreased ROS. In addition, Res significantly reduced hepatic steatosis. After Res treatment, concentrations of p47phox (membrane) and gp91phox proteins were reduced, while p-HSL, HSL and ATGL protein expression levels were increased. Mechanistically, the levels of Sirt1, p-AMPK and p-FOXO1 expression in the liver tissues were up-regulated following supplementation with Res, and FOXO1 protein was released from the nucleus into the cytoplasm. CONCLUSIONS: Res is able to attenuate hepatic steatosis and lipid metabolic disorder and enhance the antioxidant ability in KKAy mice, possibly by up-regulating Sirt1 expression and the phosphorylation of AMPK. PMID- 25140192 TI - Navigating diabetes-related immune epitope data: resources and tools provided by the Immune Epitope Database (IEDB). AB - BACKGROUND: The Immune Epitope Database (IEDB), originally focused on infectious diseases, was recently expanded to allergy, transplantation and autoimmunity diseases. Here we focus on diabetes, chosen as a prototype autoimmune disease. We utilize a combined tutorial and meta-analysis format, which demonstrates how common questions, related to diabetes epitopes can be answered. RESULTS: A total of 409 references are captured in the IEDB describing >2,500 epitopes from diabetes associated antigens. The vast majority of data were derived from GAD, insulin, IA-2/PTPRN, IGRP, ZnT8, HSP, and ICA-1, and the experiments related to T cell epitopes and MHC binding far outnumbers B cell assays. We illustrate how to search by specific antigens, epitopes or host. Other examples include searching for tetramers or epitopes restricted by specific alleles or assays of interest, or searching based on the clinical status of the host. CONCLUSIONS: The inventory of all published diabetes epitope data facilitates its access for the scientific community. While the global collection of primary data from the literature reflects potential investigational biases present in the literature, the flexible search approach allows users to perform queries tailored to their preferences, including or excluding data as appropriate. Moreover, the analysis highlights knowledge gaps and identifies areas for future investigation. PMID- 25140193 TI - Optimal treatment strategy for a tumor model under immune suppression. AB - We propose a mathematical model describing tumor-immune interactions under immune suppression. These days evidences indicate that the immune suppression related to cancer contributes to its progression. The mathematical model for tumor-immune interactions would provide a new methodology for more sophisticated treatment options of cancer. To do this we have developed a system of 11 ordinary differential equations including the movement, interaction, and activation of NK cells, CD8(+)T-cells, CD4(+)T cells, regulatory T cells, and dendritic cells under the presence of tumor and cytokines and the immune interactions. In addition, we apply two control therapies, immunotherapy and chemotherapy to the model in order to control growth of tumor. Using optimal control theory and numerical simulations, we obtain appropriate treatment strategies according to the ratio of the cost for two therapies, which suggest an optimal timing of each administration for the two types of models, without and with immunosuppressive effects. These results mean that the immune suppression can have an influence on treatment strategies for cancer. PMID- 25140194 TI - A biological hierarchical model based underwater moving object detection. AB - Underwater moving object detection is the key for many underwater computer vision tasks, such as object recognizing, locating, and tracking. Considering the super ability in visual sensing of the underwater habitats, the visual mechanism of aquatic animals is generally regarded as the cue for establishing bionic models which are more adaptive to the underwater environments. However, the low accuracy rate and the absence of the prior knowledge learning limit their adaptation in underwater applications. Aiming to solve the problems originated from the inhomogeneous lumination and the unstable background, the mechanism of the visual information sensing and processing pattern from the eye of frogs are imitated to produce a hierarchical background model for detecting underwater objects. Firstly, the image is segmented into several subblocks. The intensity information is extracted for establishing background model which could roughly identify the object and the background regions. The texture feature of each pixel in the rough object region is further analyzed to generate the object contour precisely. Experimental results demonstrate that the proposed method gives a better performance. Compared to the traditional Gaussian background model, the completeness of the object detection is 97.92% with only 0.94% of the background region that is included in the detection results. PMID- 25140195 TI - Effects of first-time overnight CPAP therapy for increasing the complexity of the patient's physiological system. AB - Studies regarding the effects of short-term continuous positive airway pressure (CPAP) therapy are not sufficient. A total of 35 patients with moderate to severe untreated OSA were divided into 2 groups. Group 1 comprised 22 patients who underwent polysomnography (PSG) for one night, and Group 2 comprised 13 patients who received PSG combined with CPAP therapy. To evaluate the influence of receiving CPAP therapy for one night, we measured 5 min wrist pulse signals before and after the experiment to assess heart rate variability, as well as novel short time multiscale entropy (sMSE) indicator that examines complexity in physiological signals. The results show that the participants in Group 1 exhibited significant changes in normalized low-frequency power/normalized high frequency power (nLF/nHF) (0.72 +/- 0.09 versus 1.11 +/- 0.11, P = 0.006) values before and after the PSG study. By contrast, the participants in Group 2 showed no significant changes in the 3 indicators. Regarding the sMSE indicator, Group 2 patients exhibited significant increases in the sMSE. CPAP therapy administered for one night can reduce the sympathovagal imbalance in patients with moderate to severe untreated OSA and increase the complexity of the patient's physiological system, thereby reflecting their overall improved health. PMID- 25140196 TI - Isolated dissection of the superior mesenteric artery treated using open emergency surgery. AB - BACKGROUND: Isolated dissection of the superior mesenteric artery (IDSMA) remains a rare diagnosis. However, new diagnostic means such as computed tomography makes it possible to detect even asymptomatic patients. If patients present symptomatic on admission, the risk of bowel infarction makes immediate therapy necessary. Today, endovascular techniques are often successfully used; however, open surgery remains important for special indications. In this paper, we present two cases with IDSMA and show why open surgical repair is still important in current treatment concepts. METHODS: Two cases with ISDMA that presented in our department from January 1, 2014 to June 1, 2014 are described. Data collection was performed retrospectively. Additionally, a review of articles which reported small cases series on patients with IDSMA within the past five years is provided. RESULTS: Both patients underwent open surgical repair following interdisciplinary consultation. Both patients were transferred to the intensive care unit after surgical repair and needed bowel rest, nasogastric suction and intravenous fluid therapy. CT scans were performed within the first week after operation. Platelet aggregation inhibitors were used in both cases as postoperative medication. Both patients survived and are able to participate in everyday activities. CONCLUSION: Open surgical repair remains important in cases of anatomic variants of visceral arteries and suspected bowel infarction. Therefore, it is important that knowledge about open surgical techniques still be taught and trained. PMID- 25140197 TI - Decitabine and SAHA-induced apoptosis is accompanied by survivin downregulation and potentiated by ATRA in p53-deficient cells. AB - While p53-dependent apoptosis is triggered by combination of methyltransferase inhibitor decitabine (DAC) and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in leukemic cell line CML-T1, reactive oxygen species (ROS) generation as well as survivin and Bcl-2 deregulation participated in DAC + SAHA-induced apoptosis in p53-deficient HL-60 cell line. Moreover, decrease of survivin expression level is accompanied by its delocalization from centromere related position in mitotic cells suggesting that both antiapoptotic and cell cycle regulation roles of survivin are affected by DAC + SAHA action. Addition of subtoxic concentration of all-trans-retinoic acid (ATRA) increases the efficiency of DAC + SAHA combination on viability, apoptosis induction, and ROS generation in HL-60 cells but has no effect in CML-T1 cell line. Peripheral blood lymphocytes from healthy donors showed no damage induced by DAC + SAHA + ATRA combination. Therefore, combination of ATRA with DAC and SAHA represents promising tool for therapy of leukemic disease with nonfunctional p53 signalization. PMID- 25140199 TI - Production and characterization of polyclonal antibody against a synthetic peptide from beta-actin protein. AB - OBJECTIVES: Antibodies against actin, as one of the most widely studied structural and multifunctional housekeeping proteins in eukaryotic cells, are used as internal loading controls in western blot analyses. The aim of this study was to produce polyclonal antibody against a synthetic peptide derived from N terminal region of beta-actin protein to be used as a protein loading control in western blot and other assay systems. MATERIALS AND METHODS: A synthetic peptide derived from beta-actin protein was designed and conjugated to Keyhole limpet hemocyanin (KLH) and used to immunize a white New Zealand rabbit. The antibody was purified from serum by affinity chromatography column. The purity of the antibody was determined by SDS-PAGE and its ability to recognize the immunizing peptide was measured by ELISA. The reactivity of the antibody with beta-actin protein in a panel of different cell lysates was then evaluated by western blot. In addition, the reactivity of the antibody with the corresponding protein was also evaluated by Immunocytochemistry and Immunohistochemistry in different samples. RESULTS: The antibody could recognize the immunizing peptide in ELISA. It could also recognize beta-actin protein in western blot as well as in immunocytochemistry and immunohistochemistry. CONCLUSION: Our data suggest that this antibody may be used as an internal control in western blot analyses as well as in other immunological applications such as ELISA, immunocytochemistry and immunohistochemistry. PMID- 25140200 TI - Comparison of the genetic convergence between mycobacterium strains by three RFLP based methods in central province of Iran. AB - OBJECTIVES: The utilization of molecular techniques in the epidemiology of tuberculosis have provided an opportunity for using effective markers to trace the transmission of the disease. The purpose of this study was to compare the genetic patterns of Mycobacterium tuberculosis by three methods of RFLP technique. MATERIALS AND METHODS: In a cross-sectional and prospective study, 95 strains of M. tuberculosis isolates were selected for DNA fingerprinting. Extraction of DNA from Mycobacterium strains and DNA fingerprinting with IS-6110, PGRS and DR probe were performed by standard protocols. RESULTS: Overall, the diversity of RFLP among 95 tuberculosis patients were 48, 50 and 45 on the basis of IS6110, PGRS and DR patterns, respectively. Twenty of these patterns (21.1%) with IS6110-RFLP, twenty-two (23.2%) with PGRS-RFLP and seventeen (17.9%) with DR RFLP occurred with unique RFLP patterns, whereas the remaining 28 patterns were communal. The risk factors of clustering among tuberculosis patients were age < 45 years, new cases, degree of sputum smear >= 2+, and close contact. CONCLUSION: Our study demonstrated that IS6110-RFLP, PGRS-RFLP and DR-RFLP genotyping could roughly identify similar proportions of clustered (secondary) cases as well as the same risk factors for clustering. PMID- 25140201 TI - The effects of cyclooxygenase inhibitors on the gastric emptying and small intestine transit in the male rats following traumatic brain injury. AB - OBJECTIVES: This study was carried out to investigate the effects of COX-2 selective inhibitor (Celecoxib) or non-selective COX inhibitor (Ibuprofen) on gastrointestinal motility. MATERIALS AND METHODS: THE RATS WERE RANDOMLY DIVIDED INTO FIVE GROUPS INCLUDING: intact, sham, traumatic brain injury (TBI) group (intact rats under TBI), Celecoxib group (10 mg/kg), Ibuprofen group (10 mg/kg). Rats of the treatment groups received gavages at 1 hr before the TBI induction. The TBI was moderate and diffused using the Marmarou method. The gastric emptying and small intestine transit were measured by phenol red method. RESULTS: The gastric emptying didn't change following TBI induction compared to intact group. The consumption of ibuprofen or celecoxib didn't have any effect on gastric emptying compared to sham group. TBI induction didn't have any effect on the intestinal transit. Also, there was no significant difference between ibuprofen or celecoxib consumption vs. sham group (P>0.05). CONCLUSION: The COX-2 selective inhibitor (celecoxib) or non-selective COX inhibitor (ibuprofen) have no effects on gastric or small bowel transit. Further work is necessary to investigate the effects of non-selective COX inhibitors and their impact on gastrointestinal motility disorders. PMID- 25140202 TI - The effects of nano-silver and garlic administration during pregnancy on neuron apoptosis in rat offspring hippocampus. AB - OBJECTIVES: The aim of this study was to investigate the effects of nano-silver and garlic administration during pregnancy on neuron apoptosis in rat offspring hippocampus. MATERIALS AND METHODS: FIFTY PREGNANT WISTAR RATS WERE RANDOMLY DIVIDED INTO FIVE GROUPS: 1- nano-silver (N.S) group; 30 mg/kg of N.S treated via gavage. 2- Control (C) group, administrated with distilled water via gavage. 3- N.S and garlic (N.S+G) group; N.S (30 mg/kg) and garlic juice (1 ml/100 g) treated via gavage simultaneously. 4- Garlic group (G); garlic juice (1 ml/100 g) administrated via gavage, 5- normal (N) without any intervention. All the interventions were done during pregnancy (21 days). Finally, the brains of rat offspring were removed to use for nano-silver level measurement and TUNEL staining. The mean of TUNEL positive cell numbers per unit area (NA) in different regions of hippocampus were compared in all animal groups. RESULTS: The results revealed a significant increase of hippocampus nano-silver level in N.S and N.S+G groups comparing to N group (P<0.05) and a significant decrease in nano-silver level in N.S+G group comparing to N.S group (P<0.01). The number of TUNEL positive cells in the CA1, CA3, and DG fields of rat offspring hippocampus increased in N.S and N.S+G groups comparing to other ones, and also reduced significantly in N.S+G group comparing to N.S group ((Y) P< 0.01). CONCLUSION: Our results showed that co-administration of nano-silver and garlic during pregnancy may lead to reduce nano-silver induced apoptotic cells in their offspring hippocampus. PMID- 25140198 TI - The protective role of antioxidants in the defence against ROS/RNS-mediated environmental pollution. AB - Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants, such as ionising and nonionising radiation, ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and furans, polycyclic aromatic hydrocarbons, and many other compounds present in the environment. It appears that increased oxidative/nitrosative stress is often neglected mechanism by which environmental pollutants affect human health. Oxidation of and oxidative damage to cellular components and biomolecules have been suggested to be involved in the aetiology of several chronic diseases, including cancer, cardiovascular disease, cataracts, age-related macular degeneration, and aging. Several studies have demonstrated that the human body can alleviate oxidative stress using exogenous antioxidants. However, not all dietary antioxidant supplements display protective effects, for example, beta carotene for lung cancer prevention in smokers or tocopherols for photooxidative stress. In this review, we explore the increases in oxidative stress caused by exposure to environmental pollutants and the protective effects of antioxidants. PMID- 25140203 TI - The effects of tramadol on norepinephrine and MHPG releasing in locus coeruleus in formalin test in rats: a brain stereotaxic study. AB - OBJECTIVES: The relationship between tramadol, as an antinociceptive drug, and locus coeruleus (LC), the main noradrenergic nucleus of the brain that affects regulation and modulation of pain through descending noradrenergic pathways was investigated. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into four groups of 10 rats. The rats were fixed in stereotaxic instrument and then a probe was inserted into LC. Pain was induced by subcutaneous injection of 50 MUl of 2.5% formalin 40 minutes after initiation of microdialysis in right hind paw, and nociceptive pain scores were calculated every 5 minutes. Subsequently noradrenaline (NA) and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), were collected and measured by microdialysis of locus coeruleus in freely moving rats every 15 minutes during formalin injection. RESULTS: Nociceptive pain scores observed in formalin test had the highest nociceptive sensation 5 minutes after injection. Significant rises in concentrations of NA and MHPG, in samples taken between 30 and 45 min after initiation of the locus coeruleus microdialysis, coincided with the peak of the pain after injection of formalin. CONCLUSION: According to concurrency of the highest nociceptive sensation and peak of NE and MHPG concentrations, tramadol can indirectly affect the LC by blocking the pain signals from different parts of the brain such as periaqueductal gray mater, central nucleus of amygdale or the spinal cord. PMID- 25140204 TI - Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of Turkey. AB - OBJECTIVES: Ethnopharmacological field surveys demonstrated that many plants, such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp. plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus communis var. saxatilis, Viscum album (ssp. album, ssp. austriacum), are used as traditional medicine for diabetes in different regions of Anatolia. The present study was designed to evaluate the in vitro antidiabetic effects of some selected plants, tested in animal models recently. MATERIALS AND METHODS: alpha-glucosidase and alpha amylase enzyme inhibitory effects of the plant extracts were investigated and Acarbose was used as a reference drug. Additionally, radical scavenging capacities were determined using 2,2'-azino-bis(3-ethylbenzothiazoline-6 sulphonic acid) ABTS radical cation scavenging assay and total phenolic content of the extracts were evaluated using Folin Ciocalteu method. RESULTS: H. graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % +/- 2.2) on alpha-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf extract had potent alpha-amylase inhibitory effect, while the hydro-alcoholic extract of J. communis fruit showed the highest alpha-glucosidase inhibitory activity (IC50: 4.4 MUg/ml). CONCLUSION: Results indicated that, antidiabetic effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit and J. oxycedrus leaf might arise from inhibition of digestive enzymes. PMID- 25140205 TI - Gender difference in motor impairments induced by chronic administration of vinblastine. AB - OBJECTIVES: Neurotoxicity of anticancer drugs complicates treatment of cancer patients. Vinblastine (VBL) is reported to induce motor and cognitive impairments in patients receiving chronic low-dose regimen. MATERIALS AND METHODS: The effects of VBL treatment on motor, learning and memory functions of male and female Wistar rats were studied by behavioral related tests. Animals were given chronic intraperitoneal injections of VBL (0.2 mg/kg/week for 5 weeks) from postnatal day 23 to 52. Motor function was evaluated using grasping test and balancing was evaluated by the rotarod. Spatial learning and memory and anxiety like behavior were determined using Morris water maze (MWM) task and open field test, respectively. RESULTS: Administration of VBL caused severe damage to motor and balance function of male rats in comparison to female rats treated with VBL and rats treated with saline. Memory and locomotion were affected in both male and female rats compared with saline treated rats, while a sex difference was also observed in these parameters; male rats showed more impairment compared with female ones. Both male and female rats showed cognitive impairments in MWM task and no sex differences were observed in these functions. CONCLUSION: Results revealed that VBL is a potent neurotoxic agent and despite the profound effect of VBL on motor and cognitive functions, it seems that male rats are more susceptible to motor deficits induced by VBL. PMID- 25140206 TI - Frequencies of two functionally significant SNPs and their haplotypes of organic anion transporting polypeptide 1B1 SLCO1B1 gene in six ethnic groups of Pakistani population. AB - OBJECTIVES: Organic anion transporter polypeptide 1B1 (OATP1B1) encoded by solute carrier organic transporter 1B1 (SLCO1B1) gene; a transporter involved in the uptake of drugs and endogenous compounds is present in hepatocyte sinusoidal membrane. Aim of this study was to investigate the frequencies of functionally significant SNPs (388A>G and 521T>C) and their haplotypes in 6 ethnic groups of Pakistani population through the development of rapid and efficient Tetra amplification refractory mutation system (T. ARMS) genotyping assay. MATERIALS AND METHODS: Frequencies of alleles, genotype, and haplotypes of two functionally significant Single nucleotide polymorphism in 180 healthy Pakistani subjects and distributions in six ethnic groups by using a single step T. ARMS genotyping assay. RESULTS: The allelic frequency for 388A>G SNP was 50% in total Pakistani population with Single nucleotide polymorphism distributions of 9.7%, 15.1%, 19.4%, 16.1%, 18.3%, and 21.5% in Punjabi, Sindhi, Balouchi, Pathan, Kashmiri and Hazara/Baltistan groups respectively; and for 521T>C SNP it was 23.9% in total Pakistani population with distributions of 11.1%, 8.9%, 15.6%, 11.1%, 31.1% and 22.2% in Punjabi, Sindhi, Balouchi, Pathan, Kashmiri, and Hazara/Baltistan groups. Both functionally significant SNPs occurred in four major haplotypes with a frequency of 35.5% for 388A/521T (*1A), 40.5% for 388G/521T (*1B), 14.4% for 388A/521C (*5), and 9.4% for 388G/521C (*15) with varying distributions among six ethnic groups. CONCLUSION: The 388A>G and 521T>C genotypes and corresponding haplotypes are present at varying frequencies in various ethnic groups of Pakistani population. Pharmacokinetic and pharmacodynamic profiling is needed to assess and characterize the effects of these haplotypes in our population. PMID- 25140207 TI - Pantoprazole, a proton pump inhibitor, increases orthodontic tooth movement in rats. AB - OBJECTIVES: Pantoprazole, is a proton pump inhibitor (PPI) prescribed for the treatment of upper gastrointestinal disorders, which in high doses has been suggested to decrease calcium absorption leading to hypocalcaemia and therefore osteoporosis. The aim of this study was to assess whether pantoprazol, could alter the rate of orthodontic tooth movement (OTM) in rats. MATERIALS AND METHODS: A time course study was established using 72 rats which were divided into six groups of 12 samples each (four: vehicle; eight: pantoprazole + vehicle). Pantoprazole at a dose of 200 mg/kg suspended in carboxymethyl cellulose (0.25 percent) was administered by a gastric tube. The upper incisors and first molars were ligated by a 5 mm nickel-titanium closed-coil spring to deliver an initial force of 60 g. Animals were euthanized two weeks after orthodontic treatment followed by assessment of tooth movement and histomorphometric evaluation of the detached maxillae. Lateral skull radiographs were obtained once a week, starting from the first day to the 6(th) week of the study. OTM and bone density data were analyzed using independent sample t-test and repeated measures ANOVA. RESULTS: No significant changes in OTM measurements and optical density were observed in vehicle-receiving animals during the study (P=0.994). OTM was significantly increased after six weeks pantoprazole therapy which continued until the 7(th) week of the experiment (P=0.007). Optical density significantly increased in the pantoprazole-treated rats after six weeks. CONCLUSION: Long term PPI therapy at high doses could lead to osteoporosis and enhanced OTM. PMID- 25140208 TI - Mild hypothermia reduces expression of Fas/FasL and MMP-3 after cerebral ischemia reperfusion in rats. AB - OBJECTIVES: To investigate the effects of local mild hypothermia on the expression of Fas, FasL and MMP-3 after cerebral ischemia-reperfusion in rats. MATERIALS AND METHODS: Male Wistar rats were divided into sham-operated group (Sham), normothermia group (NT), and hypothermia group (HT). MCAO/R model was established by Longa's method, and reperfusion was allowed after 2 hr occlusion. Mild hypothermia (33+/-0.5 degrees C) for 6 hr was initiated at the start of reperfusion. Immunohistochemistry was performed to determine expression Fas, FasL, and MMP-3. RESULTS: Infarct volume was reduced in the hypothermia group (18.43+/-4.23%) compared with the normothermia group (24.76+/-5.76%) (P<0.05). In mild hypothermia group, numbers of Fas-positive and MMP-3 positive cells were significantly less than those of normothermia group (P<0.05). Neurological functional scores of mild hypothermia were significantly improved (P<0.05). CONCLUSION: Mild hypothermia decreases infarct volume after cerebral ischemia reperfusion, reduces Fas and MMP-3 expression, but increases FasL in cerebral ischemia-reperfusion rats. PMID- 25140209 TI - Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats. AB - OBJECTIVES: Diabetes plays an important role in the induction of the liver injury. Grape seed proanthocyanidin (GSP) have a wide range of medicinal properties against oxidative stress. In this study we evaluated antioxidant effects of GSP on liver in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were divided into three groups: control, untreated diabetic and diabetic rats treated with GSP. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (50 mg/kg). GSP were administered via oral gavage (200 mg/kg) for 4 weeks. RESULTS: GSP produced significant hepatoprotective effects by decreasing activities of serum aminotransferases and alkaline phosphatase, and decreasing liver malondialdehyde and bilirubin (P<0.05) levels. It increased liver superoxide dismutase, catalase and glutathione peroxidase activities and albumin level (P<0.05). Administration of GSP significantly ameliorated structural changes induced in liver of diabetic rats. CONCLUSION: GSP have protective effects against hepatic tissue injury due to antioxidant properties. PMID- 25140210 TI - Evaluation of alpha- amylase inhibition by Urtica dioica and Juglans regia extracts. AB - OBJECTIVES: One strategy for the treatment of diabetes is inhibition of pancreatic alpha- amylase. Plants contains different chemical constituents with potential for inhibition of alpha-amylase and hence maybe used as therapeutic. MATERIALS AND METHODS: Urtica dioica and Juglans regia Linn were tested for alpha amylase inhibition. Different concentrations of leaf aqueous extracts were incubated with enzyme substrate solution and the activity of enzyme was measured. For determination of the type of inhibition, Dixon plot was depicted. Acarbose was used as the standard inhibitor. RESULTS: Both plant extracts showed time and concentration dependent inhibition of alpha-amylase. 60% inhibition was seen with 2 mg/ml of U. dioica and 0.4 mg/ml of J. regia aqueous extract. Dixon plots revealed the type of alpha-amylase inhibition by these two extracts as competitive inhibition. CONCLUSION: Determination of the type of alpha-amylase inhibition by these plant extracts could provide by successful use of plant chemicals as drug targets. PMID- 25140211 TI - Potential effect of opium consumption on controlling diabetes and some cardiovascular risk factors in diabetic patients. AB - BACKGROUND: Due to this belief that opium may have beneficial effects on diabetes or cardiovascular risk factors, the present study aimed to assess the potential and possible effects of opium consumption on diabetes control and some cardiovascular risk factors in diabetic patients. METHODS: This study enrolled 374 diabetic subjects from diabetes care centers in Kerman, Iran, including opium user group (n = 179) and a non-opium user group (n = 195). The data were collected through a questionnaire completed by interviewing, physical examination and laboratory assessment. FINDINGS: Opium did not show any statistically significant effect on blood glucose, glycated hemoglobin (HbA1C), fasting blood sugar (FBS), low-density lipoprotein (LDL) and diastolic blood pressure. However, systolic blood pressure (SBP) and prevalence of high SBP were significantly higher in opium user group (P < 0.050). In addition, lower serum high-density lipoprotein (HDL) and frequency of lower HDL was significantly higher in opium user group (P < 0.001). CONCLUSION: According to this study, opium does not seem to have beneficial effects on diabetes control or cardiovascular risk factors. Therefore, it would not be advisable to consume opium as an anti-diabetes or cardioprotective agent. PMID- 25140212 TI - Effect of opium addiction on aspirin resistance in stable angina pectoris. AB - BACKGROUND: The rate of cardiovascular diseases in developing countries is approximately 60% and it is still has an increasing trend. The clinical effectiveness of aspirin in preventing cardiovascular events has been well proven. Although aspirin is an effective and inexpensive drug, its consumption is not equally beneficial for all patients. Many factors can be affective on the efficacy of antiplatelet drugs such as aspirin. METHODS: This study was carried out on 260 patients who had stable angina pectoris and coronary artery disease was approved by coronary angiography. Based on opium addiction, the patients were divided into two groups. Opium addiction was diagnosed base on Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. The mid stream morning urinary sample were collected for measuring the urinary 11 dehydroxy thromboxane B2 level (UTXB2). Urinary level of UTXB2 was considered as an aspirin resistance index. FINDINGS: The mean age of patients was 57.3 +/- 8.9; and 44.6% of them were females. The aspirin resistance rate was 41.5%. Significant difference in aspirin resistance was observed between the opium addicts and non-addicts. (51.5% vs. 31.5%) (P = 0.001). The effects of confounding variables such as diabetes, hypertension, and hyperlipidemia were eliminated by regression logistic multivariable analysis. CONCLUSION: The prevalence of aspirin resistance in patients with stable angina pectoris was 41.5%. The prevalence of aspirin resistance in patients with stable angina pectoris who had opium addiction was significantly higher them non-addicts. PMID- 25140213 TI - Challenges in the Area of Training and Prevention at the HIV Triangulation Clinic, Kerman, Iran. AB - BACKGROUND: Since 2000, Iran has been delivering training and treatment services, including methadone therapy, to human immunodeficiency virus (HIV) positive patients through triangular clinics. This study aims to evaluate the effectiveness of these activities at the HIV Triangulation Centre in the city of Kerman, Iran, through clients' views. METHODS: Participants were recruited using a convenience sample and assessed through in-depth interviews, and observations. Data were analyzed using a thematic analysis, matrix based method. FINDINGS: The results found problems in training and counseling which was described by the staff to be due to the effects of the economic difficulties of the clients, not being of the same sex as the consultant, and lack of utilization of a variety of training methods by the clients. Furthermore, the absorption of clients was perceived as being affected by the appearance of the center, gossip around the center, limited working hours, and interpersonal relations between clients and staff. The clients also criticized the building of the center as it failed to maintain anonymity of the patients. The need for supplementary services, such as dentistry, was perceived by many clients. CONCLUSION: The application of appropriate strategies such as providing adequate training and removing the obstacles of absorption should be taken into account to increase the utility and coverage of the triangular clinic. These interventions could be a range of activities, such as relocating the center to a more decent place and encouraging the staff to appear in a professional white coat to help gain the trust of clients. PMID- 25140214 TI - Drug Use among Residents of Juvenile Correctional Center in Kerman, Iran, and its Relationship with Personality Dimensions and Self-concept. AB - BACKGROUND: Identifying the status of substance misuse and its psychosocial correlates among residents of juvenile correctional centers, as a high risk group, could potentially illuminate the roadmap to prevention of drug use in this group. METHODS: In this cross-sectional study, 93 individuals aged 13 to 18 were enrolled. A self-administered questionnaire was completed and dropped in a sealed box. It consisted of 4 parts of Piers-Harris Children's Self-Concept Scale, NEO Personality Inventory, drug use questions, and demographic variables. All questionnaires were well adapted in the Persian language. MANOVA was used to compare the subscale scores between the drug users and nonusers. FINDINGS: All respondents were male and 40% were illiterate. More than 40% had drug dependent fathers. Use of cigarette, opium, and alcohol in the previous 30 days was reported by 31.9, 52.2, and 15.9% of respondents, respectively. In this population, the score of 3 of the 5 personality factors (i.e., neuroticism, extraversion, and openness) were higher than in the general population (P < 0.001). More than 88% of subjects had negative self-concept. Both the scores of personality and self-concept showed no significant difference based on the status of drug use. CONCLUSION: Prevalence of lifetime and last-month drug use was found to be high. Regarding the profiles of personality and self-concept, more comprehensive evidence-based interventions are needed for improvement of their mental health. PMID- 25140215 TI - The Prevalence of Musculoskeletal Pain and Forward Head Posture among Heroin Users during their Withdrawal with Methadone. AB - BACKGROUND: Heroin is an extremely addictive narcotic drug derived from morphine. Its continued use requires increased amounts of the drug to achieve the same effect, resulting in tolerance and addiction. This study was done in order to determine the prevalence of musculoskeletal pain and forward head posture among heroin users during their withdrawal. METHODS: This research was a cross sectional study that was done on 90 heroin users (83 males, 7 females) aged between 20 to 40 years (32.5 +/- 3.81) during their withdrawal in Shiraz, Iran. They were selected by simple randomized sampling. Data were collected by a form regarding age, sex, the duration of heroin use, and musculoskeletal pain. Pain was measured by VAS (visual analog scale) and forward head posture was evaluated by plumb line. Pearson correlation technique and chi-square were used for analyzing the data. FINDINGS: The results revealed that the majority of heroin users suffered from musculoskeletal pain during their withdrawal. At the end of withdrawal 53.4% had severe pain, 38.8% had moderate pain, and 7.8% of them had mild pain. Pain in the lower extremities and low back was more common than the upper extremities. The intensity of pain before withdrawal was mild, during withdrawal was moderate, and at the end was sever, but there was no significant correlation between them. The results also showed 43.3% of subjects had normal posture and 56.7% had forward posture. CONCLUSION: According to the results, the intensity of pain increased during the withdrawal period; therefore, more attention must be paid to this complication in heroin users for better evaluation and a successful withdrawal. PMID- 25140216 TI - Selection of Variables that Influence Drug Injection in Prison: Comparison of Methods with Multiple Imputed Data Sets. AB - BACKGROUND: Prisoners, compared to the general population, are at greater risk of infection. Drug injection is the main route of human immunodeficiency virus y(HIV) transmission, in particular in Iran. What would be of interest is to determine variables that govern drug injection among prisoners. However, one of the issues that challenge model building is incomplete national data sets. In this paper, we addressed the process of model development when missing data exist. METHODS: Complete data on 2720 prisoners was available. A logistic regression model was fitted and served as gold standard. We then randomly omitted 20%, and 50% of data. Missing date were imputed 10 times, applying multiple imputation by chained equations (MICE). Rubin's rule (RR) was applied to select candidate variables and to combine the results across imputed data sets. In S1, S2, and S3 methods, variables retained significant in one, five, and ten imputed data sets and were candidate for the multifactorial model. Two weighting approaches were also applied. FINDINGS: Age of onset of drug use, recent use of drug before imprisonment, being single, and length of imprisonment were significantly associated with drug injection among prisoners. All variable selection schemes were able to detect significance of these variables. CONCLUSION: We have seen that the performances of easier variable selection methods were comparable with RR. This indicates that the screening step can be used to select candidate variables for the multifactorial model. PMID- 25140217 TI - The Relationship between Perfectionism and Coping Strategies in Drug-dependent Men. AB - BACKGROUND: The aim of this study was to examine the relationship between perfectionism and coping strategies in drug-dependent men. This study is a descriptive correlational study. METHODS: The statistical population of this study consisted of all drug-dependent men (n = 6237) in years 2010-2011, who were admitted to all self-referral rehabs in Kerman, Iran. From this statistical population, 361 individuals were selected using randomized cluster sampling. The measurement tools applied in this study were positive and negative perfectionism questionnaires (Terry-Short et al) and coping responses (Blinger and Moose). FINDINGS: The data was analyzed using statistical methods, Pearson Coefficient Correlation and multivariable regression inferential statistics. The results showed that there is a significant correlation between positive and negative perfectionism and problem-focused and emotion-focused coping strategies (P <= 0.010). CONCLUSION: The results of the current study show that positive and negative perfectionism predicts problem-focused and emotion-focused coping strategies for drug-dependent men. PMID- 25140218 TI - Single and repeated ultra-rapid detoxification prevents cognitive impairment in morphine addicted rats: a privilege for single detoxification. AB - BACKGROUND: Opioids have been shown to affect learning and memory processes. Different protocols of morphine withdrawal can substantially vary in their success to prevent opioid induced impairments of cognitive performance. In the present study, we report the effects of single and repetitive ultra-rapid detoxification (URD) on spatial learning and memory in morphine addicted rats. METHODS: Morphine (10 mg/kg) was intraperitoneally (IP) injected in male rats once a day over one week and after which they were detoxified with naloxone administration under anesthesia. For the repetitive procedure, a second one week morphine treatment with a second subsequent detoxification was performed. Control groups received an equivalent volume of saline injections. Spatial learning and memory was evaluated using the Morris water maze (MWM) task. FINDINGS: Both protocols of morphine administration resulted in a severe spatial memory impairment that could be significantly prevented by both single and repetitive URD. However, memory abilities in animals treated with repetitive URD were still significantly lower than in animals of the corresponding control group. Alterations in motor activity or sensory-motor coordination between morphine treated and control animals could be ruled out by comparing swimming speed and visible platform performances that were not different between groups. Thus, URD and, specifically single URD, can prevent the spatial memory impairments in addicted rats. CONCLUSION: As opioid addiction is an extending and serious concern in many societies, these findings may have clinical values and therapeutic implications for patients who experience multiple opioid relapses. PMID- 25140219 TI - Ginger (zingiber officinale roscoe) prevents morphine-induced addictive behaviors in conditioned place preference test in rats. AB - BACKGROUND: Consumption of chronic morphine induces neuro-inflammation and addictive seeking behavior. Ginger (Zingiber Officinale Roscoe), a well-known spice plant, has been used traditionally in the treatment of a wide variety of ailments. It has been shown that ginger has anti-inflammatory, anti-oxidative and antinociceptive properties. However, its influences on morphine-induced addictive behaviors have not yet been clarified. The aim of the present study was the inhibition of exploratory behavior of morphine addiction in the conditioned place preference test in male desert rats through ginger. METHODS: For conditioning to the morphine, the male Wistar rats received morphine (12 mg/kg intraperitoneally or i.p.) for 6 consecutive days and treatment groups were given different doses of ginger (25, 50 and 100 mg/kg intragastrically or i.g.) 30 min before morphine injection. For investigating addictive seeking behavior, conditioned place preference test (CPP) was used. FINDINGS: Our result demonstrated that injection of morphine for 6 days induces dependency to morphine and creates addictive seeking behavior and ginger (100 mg/kg) could decrease time spend in conditioning box (addictive seeking behavior). CONCLUSION: The data indicated that ginger extract has a potential anti-addictive property against chronic usage of morphine. PMID- 25140220 TI - Attitudes, Practices and Perceived Barriers in Smoking Cessation among Dentists of Udaipur City, Rajasthan, India. AB - BACKGROUND: Tobacco is one of the most important causes of morbidity and mortality. Tobacco toll in India has one-fifth of all worldwide death attributed to tobacco. There are 700000 deaths per year due to smoking and 800000-900000 per year to all forms of tobacco use of exposure in India. The role of dentist in supporting their patients to quit smoking has been recognized. The present study was conducted to know the attitudes, practices and barriers in tobacco cessation among dentists of Udaipur city (Rajasthan, India). METHODS: A pretested, close ended, self-administered, coded questionnaire was distributed among all the 262 dental health practitioners and the teaching staff. Out of 262 questionnaires distributed among the dentist, 151 dentists filled out and returned the questionnaire. FINDINGS: The majority of the dentists (98.7%) agreed that it was their responsibility to provide smoking cessation counseling. 54.3% of dentists agreed that such discussions were too time consuming. 37.1% thought they lacked knowledge regarding this subject. 35.8% feared to an extent about patient leaving their clinic if counseled much. CONCLUSION: In general, the dentists had a favorable attitude in tobacco cessation counseling for the patients; however, the lack of time and knowledge and to an extent, a fear that the patients would leave their clinic, was the main identified barriers. PMID- 25140221 TI - Enucleation of eye using finger following cannabis consumption: a case report. AB - BACKGROUND: Enucleation is a topic discussed in psychiatry which is a self-injury matter. Enucleation is observed as psychotic disorder due to substance abuse. In people with mental disorders who also have substance use leading to hallucinations and delusions, unusual eye evacuation were reported. In most cases, enucleation was done using sharp tools. CASE REPORT: This report describes a man suffering from psychosis after consuming hashish and has attempted to evacuate his eyes with his finger. DISCUSSION: Given the increasing prevalence of hashish use by young people, and false beliefs about the use of hashish in order to withdraw other substances, preventive methods and education for young and vulnerable people are suggested. PMID- 25140222 TI - Nose to tail, roots to shoots: spatial descriptors for phenotypic diversity in the Biological Spatial Ontology. AB - BACKGROUND: Spatial terminology is used in anatomy to indicate precise, relative positions of structures in an organism. While these terms are often standardized within specific fields of biology, they can differ dramatically across taxa. Such differences in usage can impair our ability to unambiguously refer to anatomical position when comparing anatomy or phenotypes across species. We developed the Biological Spatial Ontology (BSPO) to standardize the description of spatial and topological relationships across taxa to enable the discovery of comparable phenotypes. RESULTS: BSPO currently contains 146 classes and 58 relations representing anatomical axes, gradients, regions, planes, sides, and surfaces. These concepts can be used at multiple biological scales and in a diversity of taxa, including plants, animals and fungi. The BSPO is used to provide a source of anatomical location descriptors for logically defining anatomical entity classes in anatomy ontologies. Spatial reasoning is further enhanced in anatomy ontologies by integrating spatial relations such as dorsal_to into class descriptions (e.g., 'dorsolateral placode' dorsal_to some 'epibranchial placode'). CONCLUSIONS: The BSPO is currently used by projects that require standardized anatomical descriptors for phenotype annotation and ontology integration across a diversity of taxa. Anatomical location classes are also useful for describing phenotypic differences, such as morphological variation in position of structures resulting from evolution within and across species. PMID- 25140223 TI - High level of treatment failure with commonly used anthelmintics on Irish sheep farms. AB - BACKGROUND: In 2013 a Technology Adoption Program for sheep farmers was established to encourage the implementation of best management practices on sheep farms in Ireland. There were 4,500 participants in this programme in 2013. As part of this programme, farmers had the option to carry out a drench test to establish the efficacy of their anthelmintic treatment. RESULTS: Flock faecal samples were collected before and after treatment administration and gastrointestinal nematode eggs enumerated. In total there were 1,893 participants in the task, however only 1,585 included both a pre- and post-treatment faecal sample. Of those, 1,308 provided information on the anthelmintic product that they used with 46%, 23% and 28% using a benzimidazole (BZ), levamisole (LEV) and macrocyclic lactone (ML) product respectively. The remaining farmers used a product inapplicable for inclusion in the task such as a flukicide or BZ/LEV combination product. Samples were included for analysis of drench efficacy if the pre-treatment flock egg count was >=200 eggs per gram and the interval post sampling was 10-14 days for BZ products, 4-7 days for LEV products and 14-18 days for ML products. These criteria reduced the number of valid tests to 369, 19.5% of all tests conducted. If the reduction post-treatment was >=95% the treatment was considered effective. Only 51% of treatments were considered effective using this criterion. There was a significant difference in efficacy between the anthelmintic drug classes with BZ effective in only 30% of treatments, LEV effective in 52% of cases and ML effective in 76% of cases. CONCLUSIONS: Gastrointestinal nematode anthelmintic treatments, as practiced on Irish farms, have a high failure rate. There was a significant difference between the efficacies of the anthelmintic classes with BZ the least effective and ML the most effective. PMID- 25140224 TI - Metastatic penile carcinoma - an update on the current diagnosis and treatment options. AB - INTRODUCTION: Penile carcinoma has an incidence of 4,000 cases in Europe. The therapy and prognosis depend decisively on the lymph node status. Lymph node metastases are detected in 23-65% cases depending on the histopathological pattern. Due to improved diagnostic methods an early detection of tumor stage is possible. Multimodal therapeutic concepts can offer curability for a subset of patients, even those suffering from advanced disease. MATERIAL AND METHODS: Current data on penile cancer based on a selective review of the literature by PubMed and the EAU guidelines 2009. RESULTS: Invasive diagnostic tools, such as fine-needle biopsy (FNB) and dynamic sentinel node biopsy (DSNB), improved the diagnosis of lymph node status considerably and reduced the morbidity in specialized centers. The application of 18F-FDG-PET/CT for metastases detection needs further evaluation due to inconsistent results. Inguinal lymphadenectomy is the therapeutic standard in case of metastases proof. It was possible to reduce the complications due to the new modified operation techniques. Patients with extended lymph node and distant metastases have a poor prognosis. Different systemic polychemotherapy regimes are applied currently and are associated with poor outcome (response rates <50%) and high morbidity. Neoadjuvant chemotherapy is recommended in patients with unresectable and relapsing lymph node metastases. CONCLUSIONS: Currently, inconsistent therapy regimens are applied for metastatic penile cancer. Standardization is urgently needed through the development of high quality studies and long-term registers in order to lower the morbidity and increase the efficiency of diagnosis and therapy. PMID- 25140225 TI - Modern diagnostic and treatment regimens are needed to achieve the best cancer and quality of life control. PMID- 25140226 TI - Significance of atypical small acinar proliferation and extensive high-grade prostatic intraepithelial neoplasm in clinical practice. AB - INTRODUCTION: Prostate cancer (PCa) is one of the most commonly diagnosed neoplasms in elderly men. The precancerous lesion of PCa is considered a high grade prostate intraepithelial neoplasm (HG-PIN), while atypical small acinar proliferation (ASAP) is commonly considered as an under-diagnosed cancer. The aim of the study was to establish the impact of ASAP and extensive HG-PIN on pre biopsy prostate-specific antigen (PSA) levels and the risk of cancer development in subsequent biopseis. MATERIAL AND METHODS: The 1,010 men suspected for PCa were included in the study based on elevated PSA, and/or positive rectal examination. Transrectal ultrasound (TRUS) guided 10 core biopsy was performed. In those with extensive HG-PIN or ASAP on the first biopsy, and/or elevated PSA value, a second biopsy was performed. RESULTS: In the second biopsy, PCa was diagnosed in 6 of 19 patients (31.57%) with extensive HG-PIN, in four of 40 (10%) with BPH, and in 4 of 18 (22.22%) with ASAP. There was a statistically significant difference between the values of PSA in the group of patients with ASAP in comparison to those with benign prostate hyperplasia (BPH) (p = 0.005) as well as in patients with HG-PIN in comparison to BPH (p = 0.02). CONCLUSIONS: A precancerous lesion diagnosed upon biopsy causes a statistically significant increase in the values of PSA in relation to BPH, as well as in the case of ASAP and extensive HG-PIN. The estimate of risk of PCa diagnosis in patients with ASAP and those with extensive HG-PIN in the first biopsy is comparable, which is why there are no reasons for different treatment of patients with the above-mentioned diagnoses. Both should be subjected to urgent second biopsy in around the 4-6 weeks following the initial biopsy. PMID- 25140227 TI - Usage of invisible near infrared light (NIR) fluorescence with indocyanine green (ICG) and methylene blue (MB) in urological oncology. Part 1. AB - INTRODUCTION: Near infrared (NIR) technology has recently garnered much interest as a tool for intraoperative image-guided surgery in various surgical sub disciplines. In urology, although nascent, NIR technology is also fostering much enthusiasm. This review discusses the two major fluorophores, indocyanine green (ICG) and methlyene blue (MB), with NIR guidance in experimental and clinical urology. The authors aim to illustrate and analyze the currently available initial studies to better understand the potential and practicability of NIR guided imaging in the diagnosis and surgical outcome improvement. In the first part of the study we analyzed problems associated with sentinel lymph node biopsy, NIR-guided detection and imaging of tumors. MATERIAL AND METHODS: PubMed and Medline databases were searched for ICG and MB use in urological settings, along with data published in abstracts of urological conferences. RESULTS: Although NIR-guided ICG and MB are still in their initial phases, there have been significant developments in major domains of urology, including uro-oncological surgery: 1) sentinel lymph node biopsy, 2) detection and imaging of tumors. CONCLUSIONS: Much like in other fields of surgical medicine, the application of NIR technology in urology is at its early stages. Therefore, more studies are needed to assess the true potential and limitations of the technology. However, initial developments hint towards a pioneering tool that may influence various aspects of urology. PMID- 25140228 TI - Pfannenstiel incision for radical retropubic prostatectomy as a surgical and cosmetic alternative to the midline or laparoscopic approach: A single center study. AB - OBJECTIVES: The Pfannenstiel incision is not a very common approach for radical retropubic prostatectomy (RPE). This study is primarily dealing with the approach to the prostate. MATERIAL AND METHODS: A 10-12 cm Pfannenstiel incision was made 2 fingers above the pubic bone. The rectus sheath was opened transversally and dissected from the rectus muscle. The muscle was further on divided in the midline; otherwise, the operation was performed the same way as the retropubic radical prostatectomy described by Walsh [1]. The wound closure was performed in several layers, and the skin was stapled. RESULTS: In a series of 163 RPEs, we achieved excellent cosmetic results. Four patients developed subcutaneous hematomas, two of them required surgical intervention, and 3 patients developed infections that were effectively treated with antibiotics. CONCLUSIONS: Our experience with the Pfannenstiel incision approach for radical retropubic prostatectomy was very positive. The approach provides good exposure, heals well with a cosmetic scar, and facilitates hernia repair through the same approach if needed. PMID- 25140229 TI - Adrenergic crisis due to pheochromocytoma - practical aspects. A short review. AB - INTRODUCTION: The definitive therapy in case of pheochromocytoma is complete surgical resection. Improper preoperative assessment and medical management generally places the patient at risk for complications, resulting from an adrenergic crisis. Therefore, it is crucial to adequately optimize these patients before surgery. Optimal preoperative medical management significantly decreases morbidity and mortality during the tumor resection. MATERIAL AND METHODS: This review addresses current knowledge in pre- and intraoperative assessment of a patient with pheochromocytoma. RESULTS: Before surgery the patient is conventionally prepared with alpha-adrenergic blockade (over 10-14 days) and subsequently, additional beta-adrenergic blockade is required to treat any associated tachyarrhythmias. In preoperative assessment, it is obligatory to monitor arterial blood pressure, heart rate, and arrhythmias and to restore the blood volume to normal. CONCLUSIONS: In conclusion, due to the pathophysiological complexity of a pheochromocytoma, the strict cooperation between the cardiologist, endocrinologist, surgeon and the anaesthesiologist for an uneventful outcome should be achieved in patients qualified for the surgical removal of such a tumor. PMID- 25140230 TI - Management and follow up of extra-adrenal phaeochromocytoma. AB - INTRODUCTION: The prevalence of phaeochromocytoma (PCC) in patients with hypertension is 0.1-0.6% and about 10% of PCCs are detected in extra-adrenal tissue. The diagnosis and therapy of this rare disease detected as a retroperitoneal tumor mass can be difficult for clinicians. MATERIAL AND METHODS: A PubMed database was searched for the peer-reviewed articles, the listed articles until Dec 2012 were included. Following key words were used: "extra adrenal phaeochromocytoma", "paraganglioma", "diagnosis", "therapy", "surgery", "genetic analysis", and "SDH mutation". RESULTS: Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) are first choice imaging tools for PCC (sensitivity 90-100%). For the validation of the diagnosis or follow up, the functional imaging 123I-metaiodobenzylguanidine (MIBG) or Fluorine-18-L dihydroxyphenylalanine (18F-DOPA) positron emission tomography (excellent specificity and sensitivity of 90-100% in detection of small tumors >1-2 cm) are used. Laparoscopic surgery with complete resection is a safe and a first choice approach. The conversion (about 5%) to direct open operation was needed for large lesions (>8 cm) with the suspicion of malignancy. Currently, there are no histological criteria for distinguishing benign and malignant tumors. The genetic testing (Sanger DNA sequencing) for hereditary syndromes (von Hippel-Lindau, neurofibromatosis, etc.) is used for prediction of malignancy and recurrence. All patients should get individual and risk-adapted genetic analysis and consultation, including family members. The rate of malignancy in ePCC is about 30% (PCC about 5-10%). In patients with proven SDHB germline mutations, higher malignancy rate, multiple PCCs and recurrences are likely. A stringent lifelong clinical follow-up is recommended in these cases. Patients with syndromic hereditary forms should be screened for other often associated neoplasms. CONCLUSIONS: New imaging tools and genetic analysis are crucial to improve the diagnosis and prognosis of phaeochromocytoma. PMID- 25140231 TI - Diagnosis of extra-adrenal phaeochromocytoma after nephrectomy. AB - This case describes a 50-yr-old man who was admitted to the Urology Ward upon the suspicion of a left kidney tumor. As part of the pre-operative check-up, an ultrasound and computed tomography of the kidneys were conducted. The results confirmed the initial diagnosis. The postoperative diagnosis was extra-adrenal pararenal phaeochromocytoma (ePCC) with succinate dehydrogenase complex, subunit B (SDHB) gene mutation. During the follow-up, a second tumor was detected by 3,4 dihydroxy-6-F-18-fluoro-L-phenylalanine positron emission tomography/computed tomography F-DOPA-PET CT that resulted in another surgery with complete resection of the tumor. The patient and his family were counseled by a genetic laboratory and remain under surveillance. PMID- 25140233 TI - Lower urinary tract symptoms and their severity in men subjected to prostate biopsy. AB - INTRODUCTION: Lower urinary tract symptoms (LUTS) are one of most frequent complaints among men over 50 years of age. They usually result from benign prostate hyperplasia, which often coexists with cancer. The aim of the present study is to evaluate prospectively the incidence of LUTS and their character in men subjected to prostate biopsy. MATERIAL AND METHODS: Data of men who were subjected to transrectal ultrasound guided prostate core biopsy from 1st July 2007 to 30th July 2008 in selected urological departments in Poland were analyzed. LUTS were measured with International Prostate Symptom Score (IPSS). RESULTS: Prostate biopsy was performed in 747 men aged between 34 and 93 years (mean - 67.4; median - 68). LUTS of mild degree or no LUTS (<=7 IPSS points) were reported by 29.5% of patients. PCa was found in 60.0% of them. Among men with moderate or severe LUTS (IPSS >7 points), PCa was found in 51.4% and 55.0% of them respectively. Median PSA was 9.5 ng/ml, 9.4 ng/ml and 12.0 ng/ml in men with mild, moderate and severe LUTS respectively (NS). However, among men with severe LUTS, PCa was more likely to be less differentiated and locally advanced. CONCLUSIONS: LUTS are weak predictors of a positive result of transrectal ultrasound guided prostate biopsy. However, there is a trend to diagnose more locally advanced and less highly differentiated cancers among men with severe lower urinary tract symptoms. PMID- 25140234 TI - The presence of LUTS is not a decisive tool for deciding who should be qualified for prostate biopsy. PMID- 25140232 TI - Tadalafil in the management of lower urinary tract symptoms: a review of the literature and current practices in Russia. AB - INTRODUCTION: Strong epidemiologic evidence supports correlation between lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) and erectile dysfunction (ED). The link has biologic plausibility given phosphodiesterase type 5 (PDE5) expression in pelvic structures. PDE5 inhibitors target pathophysiologic processes implicated in LUTS/BPH. MATERIAL AND METHODS: This review highlights the efficacy and safety of the daily use of a PDE5 inhibitor tadalafil in LUTS/BPH, with a focus on LUTS/BPH medical management in Russia. RESULTS: Alpha-blockers and phytotherapy are major components of the current LUTS/BPH therapy in Russia. Russian regulatory authorities granted approval for once-daily tadalafil for treatment of LUTS/BPH in January 2012. In a pivotal study, tadalafil 5 mg once-daily significantly improved International Prostate Symptom Score (IPSS) over 12 weeks vs. placebo (P = .004) regardless of baseline ED severity. IPSS improvement was maintained at 12 weeks. Integrated analysis of randomized studies showed that tadalafil 5 mg once-daily resulted in significant symptom improvements across a range of men with LUTS/BPH. Relief of LUTS due to tadalafil was independent of improvement in ED; improvements in IPSS and erectile function were only weakly correlated (r = -0.229). Another pooled analysis found similar improvement in LUTS/BPH between men with or without ED, with non-significant P values for treatment-by-ED-status interactions for total IPSS ( P = .73). Non-registration studies of tadalafil and alpha-blocker co therapy in LUTS/BPH suggest an additive effect, but co-therapy is not recommended in current tadalafil prescribing instructions. CONCLUSIONS: Tadalafil results in symptom improvements across a range of men with LUTS/BPH and represents a new treatment option for patients in Russia with LUTS/BPH. PMID- 25140235 TI - Secondary infertility and the aging male, overview. AB - INTRODUCTION: Old men preparing themselves for marriage late in their lives might face infertility. Infertility in this group of men should be considered from a wider perspective, as they face any age-related health troubles that include, but are not limited to, androgen deficiency and psychological disorders that impede early conception. This review aims to shed light on the proper approach to this minority of secondarily infertile men. MATERIAL AND METHODS: A comprehensive electronic English literature search was conducted, using various medical websites and books, for the factors that cause infertility in senior fathers. The physiology of geriatric males, together with their common comorbidities, were discussed. RESULTS: Old men presenting with secondary infertility should be approached differently. Aging, itself, has a significant impact on male sexual function, sperm parameters, and fertility; all of which contribute to poor fecundability, decreased fertilizing capacity, increased time to pregnancy, increased rate of DNA damage, high abortion rates and increased prevalence of fetal developmental failures. The complexity and the unknowns of the aging male physiology, together with the interaction of obstinate diseases the patient might have, make the issue very difficult to tackle. CONCLUSIONS: Management should include the conventional way of treating young sufferers and further target the underlying causes, if known, along with the provision of geriatric, psychologic, and andrologic support. PMID- 25140236 TI - Sexology of elderly man with secondary infertility. PMID- 25140237 TI - Conservative management of accidental gall bladder puncture during percutaneous nephrolithotomy. AB - Percutaneous nephrolithotomy (PCNL) has been an excellent option for the management of kidney stones. There have been many complications in regards to solid organ injury during PCNL. Here we discuss an interesting case of 45-year old woman, who underwent PCNL for right renal staghorn calculus, and had an accidental puncture of the gall bladder. Post operatively, the patient was conservatively managed and recovered well. A small number of cases has been reported until now in literature. PMID- 25140238 TI - Getting access in PNL - eyes wide shut. PMID- 25140239 TI - Make the technology count. PMID- 25140240 TI - Infected urachal cyst in a young adult. AB - The urachus is the remnant of the cloaca, which in adults attaches the bladder dome to the umbilicus. After birth it obliterates and presents as the midline umbilical ligament. Patent urachal anomalies are usually detected in childhood. In adults they occur very rarely and the presentation and diagnosis may be occasionally challenging. We present and discuss the case of an infected urachal cyst found in a 30-year-old adult. PMID- 25140241 TI - Use of Martius flap in the complex female urethral surgery. AB - INTRODUCTION: Objectives were to evaluate safety and patient reported perception of the Martius fibroadipose flap for complex female urethra reconstruction. MATERIAL AND METHODS: Patients operated with a Martius flap were contacted again via telephone to rate their self-perception on cosmetic appearance, pain or numbness of the flap harvest site. RESULTS: 37 women (mean age of 46.8 yrs.) were operated with Martius flaps. Complications were limited to bleeding from the flap bed in 19% (7/37); hematomas - 5.4% (2/37); and lymphorrhea from the labial incision in 13.5% (5/37) and labial wound infection in 5.4% of cases (2/37). For self-perception 65% of patients (24/37) were phone interviewed (mean follow up - 54.2 months). Only 17% of women (4/24) complained to cosmetic problems. Two patients (8%) complained to a periodical mild pain. And 12.5% (3/24) of the women had decreased sensation or numbness at the labia. CONCLUSIONS: Martius flap is safe and it is not causing significant complications during female urethral reconstruction. However, an informed consent for decreased sensation and numbness at the flap harvesting area should be obtained. PMID- 25140242 TI - Use of Martius flaps in complex female urethral surgery and the tethered vagina syndrome. PMID- 25140243 TI - Renal function recovery after laparosocopic pyeloplasty. AB - INTRODUCTION: To observe the renal function recovery measured by diuretic renography in short and medium follow-up of patients with transperitoneal Anderson-Hynes laparoscopic pyeloplasty. MATERIAL AND METHODS: WE PERFORMED A RETROSPECTIVE REVIEW FROM OUR SERIES OF LAPAROSCOPIC PYELOPLASTIES, AND WE APPLIED THE FOLLOWING SELECTION CRITERIA: 1) to have at least two MAG3 diuretic renography during the follow-up, performed with a gap of 4-6 months between them; 2) to have at least one year follow-up. Fulfilling these criteria, we have selected 35 patents of 62. RESULTS: During follow-up, statistically significant improvement comparing with the pre-surgical value has been observed in diuretic renography in the operated kidney in all selected patients during the time of follow up in terms of: functional uptake ratio (FUR), furosemide excretion and total excretion. No statistically significant differences were found in excretion time and spontaneous excretion parameters. By dividing patients in two age groups <40 years and >40 years we found no statistically significant differences between them in relation to the improvement of the FUR. CONCLUSIONS: Laparoscopic pyeloplasty not only corrects the UPJO, it also may recover renal function demonstrated after one year follow up with diuretic renography. Laparoscopic pyeloplasty should be procedure of choice even in those patients with poor renal function at diagnosis, whenever there are chances of recovering renal function, regardless patients age. PMID- 25140244 TI - Letter to the editor. PMID- 25140245 TI - Sex and psychotropic drugs and relationship blues. PMID- 25140246 TI - Sustained-release corticosteroid options. AB - Sustained-release corticosteroid treatment has shown to be a promising strategy for macular edema due to retinovascular disease (i.e., diabetes and retinal vein occlusion) and for the treatment of noninfectious posterior uveitis. Clinicians now have the option of three sustained-release corticosteroid implants: Ozurdex (Allergan Inc., Irvine, CA) which releases dexamethasone and two devices that release fluocinolone acetonide, Retisert (Bausch & Lomb, Rochester, NY), and Iluvien (Alimera Science, Alpharetta, GA). Each has different physical characteristics and duration effect and has been approved for different indications. Herein we provide a summary of the current clinical knowledge regarding these implants. PMID- 25140247 TI - Eye movement control. PMID- 25140248 TI - Prevalence of psychiatric morbidities in acute coronary heart disease. AB - Introduction. Psychiatric problems and stresses may deteriorate the prognosis of patients with IHD. So evaluating their frequency possibly will promote our perspective regarding their vital importance in the field of consultation-liaison psychiatry. Method and Materials. One hundred and one (101) patients with IHD were interviewed in CCU of a general hospital by a psychiatrist to find whether there was any relationship between cardiac events and psychiatric problems or stresses. Results. Cardiac events were significantly more prevalent among patients with both psychiatric problems and biological risk factors (P < 0.05). Also, the number of patients suffering from psychiatric problems was significantly more than cases without that (P < 0.05). There was a significant difference between male and female patients regarding the type of stress (P < 0.01). 79% of total stresses were experienced by patients who had as well psychiatric problems (P < 0.0001). In addition, there was significantly more dysthymic disorder in the acute group of patients in comparison with major or minor depressive disorder in the chronic group (P < 0.001). Conclusion. The high prevalence of psychiatric problems and psychosocial stresses among patients with IHD deserves sufficient attention by clinicians for detection, monitoring, and management of them. PMID- 25140249 TI - Light to moderate alcohol consumption is protective for type 2 diabetes mellitus in normal weight and overweight individuals but not the obese. AB - OBJECTIVE: To examine the association between alcohol consumption and risk of type 2 diabetes mellitus (T2DM) overall and by body mass index. METHODS: Cross sectional study of employed individuals. Daily alcohol intakes were calculated from a self-administered food frequency questionnaire by 5,512 Maori, Pacific Island, and European workers (3,992 men, 1520 women) aged 40 years and above. RESULTS: There were 170 new cases of T2DM. Compared to the group with no alcohol consumption and adjusting for age, sex, and ethnicity, the group consuming alcohol had relative risks of T2DM of 0.23 (95% CI: 0.08, 0.65) in normal weight individuals, 0.38 (0.18, 0.81) in overweight individuals, and 0.99 (0.59, 1.67) in obese individuals. After further adjusting for total cholesterol, HDL cholesterol, triglycerides, smoking habit, physical activity, socioeconomic status, body mass index, and hypertension, the relative risks of T2DM were 0.16 (0.05, 0.50) in normal weight individuals, 0.43 (0.19, 0.97) in overweight individuals, and 0.92 (0.52, 1.60) in overweight individuals. Across the categories of alcohol consumption, there was an approximate U-shaped relationship for new cases of T2DM. There was no significant association between alcohol consumption and IGT. CONCLUSIONS: Alcohol consumption was protective against diagnosis of T2DM in normal and overweight individuals but not in the obese. PMID- 25140250 TI - Extent of Anaemia among Preschool Children in EAG States, India: A Challenge to Policy Makers. AB - Background. India is the highest contributor to child anemia. About 89 million children in India are anemic. The study determines the factors that contributed to child anemia and examines the role of the existing programs in reducing the prevalence of child anemia particularly in the EAG states. Methods. The data from the latest round of the National Family Health Survey (NFHS-3) is used. Simple bivariate and multinomial logistics regression analyses are used. Results. About 70% children are anemic in all the EAG states. The prevalence of severe anemia is the highest (6.7%) in Rajasthan followed by Uttar Pradesh (3.6%) and Madhya Pradesh (3.4%). Children aged 12 to 17 months are significantly seven times (RR = 7.99, P < 0.001) more likely to be severely anemic compared to children of 36 to 59 months. Children of severely anemic mothers are also found to be more severely anemic (RR = 15.97, P < 0.001) than the children of not anemic mothers. Conclusions. The study reveals that the existing government program fails to control anemia among preschool children in the backward states of India. Therefore, there is an urgent need for monitoring of program in regular interval, particularly for EAG states to reduce the prevalence of anemia among preschool children. PMID- 25140251 TI - Novel axillary approach for brachial plexus in robotic surgery: a cadaveric experiment. AB - Brachial plexus surgery using the da Vinci surgical robot is a new procedure. Although the supraclavicular approach is a well known described and used procedure for robotic surgery, axillary approach was unknown for brachial plexus surgery. A cadaveric study was planned to evaluate the robotic axillary approach for brachial plexus surgery. Our results showed that robotic surgery is a very useful method and should be used routinely for brachial plexus surgery and particularly for thoracic outlet syndrome. However, we emphasize that new instruments should be designed and further studies are needed to evaluate in vivo results. PMID- 25140252 TI - Knowledge and perception on long acting and permanent contraceptive methods in adigrat town, tigray, northern ethiopia: a qualitative study. AB - Background. Long acting and permanent contraceptive methods have the potential to reduce unintended pregnancies but the contraceptive choice and utilization in Ethiopia are highly dominated by short term contraceptives. Objective. To assess the knowledge and perception on long acting and permanent contraceptives of married women and men in Northern Ethiopia. Method. A qualitative method was conducted in Adigrat on January, 2012. Four focus group discussions with married women and men and six in-depth interviews with family planning providers were conducted. Content analysis was used to synthesize the data. Result. Participants' knowledge on long acting and permanent contraceptives is limited to recognizing the name of the methods. Most of the participants are not able to identify permanent methods as a method of contraception. They lack basic information on how these methods work and how they can use it. Women had fears and rumors about each of these methods. They prefer methods which do not require any procedure. Family planning providers stated as they have weakness on counseling of all contraceptive choices. Conclusion. There are personal barriers and knowledge gaps on these contraceptive methods. Improving the counseling service program can help women to increase knowledge and avoid misconceptions of each contraceptive choice. PMID- 25140253 TI - High Steroid Sensitivity among Children with Nephrotic Syndrome in Southwestern Nigeria. AB - Recent reports from both Caucasian and black populations suggest changes in steroid responsiveness of childhood nephrotic syndrome. This study was therefore undertaken to determine the features and steroid sensitivity pattern of a cohort of black children with nephrotic syndrome. Records of children managed for nephrotic syndrome from January 2008 to April 2013 were reviewed. Details including age, response to treatment, and renal histology were analysed. There were 108 children (median age: 5.9 years, peak: 1-2 years), 90.2% of whom had idiopathic nephrotic syndrome. Steroid sensitivity was 82.8% among children with idiopathic nephrotic syndrome but 75.9% overall. Median time to remission was 7 days. Median age was significantly lower in steroid sensitive compared with resistant patients. The predominant histologic finding in resistant cases was focal segmental glomerulosclerosis (53.3%). No cases of quartan malaria nephropathy or hepatitis B virus nephropathy were diagnosed. Overall mortality was 6.5%. In conclusion, unusually high steroid sensitivity is reported among a cohort of black children. This is likely attributable to the lower age structure of our cohort as well as possible changing epidemiology of some other childhood diseases. Surveillance of the epidemiology of childhood nephrotic syndrome and corresponding modifications in practice are therefore recommended. PMID- 25140254 TI - Occipital Artery Function during the Development of 2-Kidney, 1-Clip Hypertension in Rats. AB - This study compared the contractile responses elicited by angiotensin II (AII), arginine vasopressin (AVP), and 5-hydroxytryptamine (5-HT) in isolated occipital arteries (OAs) from sham-operated (SHAM) and 2-kidney, 1-clip (2K-1C) hypertensive rats. OAs were isolated and bisected into proximal segments (closer to the common carotid artery) and distal segments (closer to the nodose ganglion) and mounted separately on myographs. On day 9, 2K-1C rats had higher mean arterial blood pressures, heart rates, and plasma renin concentrations than SHAM rats. The contractile responses to AII were markedly diminished in both proximal and distal segments of OAs from 2K-1C rats as compared to those from SHAM rats. The responses elicited by AVP were substantially greater in distal than in proximal segments of OAs from SHAM rats and that AVP elicited similar responses in OA segments from 2K-1C rats. The responses elicited by 5-HT were similar in proximal and distal segments from SHAM and 2K-1C rats. These results demonstrate that continued exposure to circulating AII and AVP in 2K-1C rats reduces the contractile efficacy of AII but not AVP or 5-HT. The diminished responsiveness to AII may alter the physiological status of OAs in vivo. PMID- 25140255 TI - Acute stroke care and thrombolytic therapy use in a tertiary care center in Lebanon. AB - Background. Thrombolytic therapy (rt-PA) is approved for ischemic stroke presenting within 4.5 hours of symptoms onset. The rate of utilization of rt-PA is not well described in developing countries. Objectives. Our study examined patient characteristics and outcomes in addition to barriers to rt-PA utilization in a tertiary care center in Beirut, Lebanon. Methods. A retrospective chart review of all adult patients admitted to the emergency department during a one year period (June 1st, 2009, to June 1st, 2010) with a final discharge diagnosis of ischemic stroke was completed. Descriptive analysis was done followed by a comparison of two groups (IV rt-PA and no IV rt-PA). Results. During the study period, 87 patients met the inclusion criteria and thus were included in the study. The mean age was found to be 71.9 years (SD = 11.8). Most patients arrived by private transport (85.1%). Weakness and loss of speech were the most common presenting signs (56.3%). Thirty-three patients (37.9%) presented within 4.5 hours of symptom onset. Nine patients (10.3%, 95% CI (5.5-18.5)) received rt-PA. The two groups (rt-PA versus non rt-PA) had similar outcomes (mortality, symptomatic intracerebral hemorrhage, modified Rankin scale scores, and residual deficit at hospital discharge). Conclusion. In our setting, rt-PA utilization was higher than expected. Delayed presentation was the main barrier to rt-PA administration. Public education regarding stroke is needed to decrease time from symptoms onset to ED presentation and potentially improve outcomes further. PMID- 25140256 TI - Isolation and characterization of bacteriophages infecting nocardioforms in wastewater treatment plant. AB - Activated sludge plants (ASP) are associated with the stable foaming problem worldwide. Apart from the physical and chemical treatment methods, biological treatment method has been least explored and may prove to be a novel and ecofriendly approach to tackle the problem of stable foam formation. In ASP Nocardia species are commonly found and are one of the major causes for forming sticky and stable foam. This study describes the isolation and characterization of three Nocardia bacteriophages NOC1, NOC2, and NOC3 for the control of Nocardia species. The bacteriophages isolated in this study have shown promising results in controlling foam producing bacterial growth under laboratory conditions, suggesting that it may prove useful in the field as an alternative biocontrol agent to reduce the foaming problem. To the best of our knowledge to date no work has been published from India related to biological approach for the control of foaming. PMID- 25140257 TI - Iranian patients require more pertinent care to prevent type 2 diabetes complications. AB - Background. Accurate care of patients with type 2 diabetes may reduce risk of complications. This study was conducted to envisage current status of cares that are provided for a sample of Iranian patients with type 2 diabetes and highlight the domains that need to be focused on in the country's national type 2 diabetes care program. Methods. Behavioral risk factors and diabetes related complications were investigated among 234 randomly selected type 2 diabetic patients residing in the city of Khoy, Northwest of Iran. Data were collected by a semistructured questionnaire in face to face or telephone interview. Proportions and confidence intervals of the observed difference were calculated by the Confidence Interval Analysis (CIA) software version 2.2.0. Results. Diabetes complications were evident amongst 67.2% of the patients. Inappropriate dietary pattern, insufficient physical activity, and anxiety were reported by 26.5%, 74.8%, and 69.7% of the respondents. Quality of life was reported to be affected in 94.6% of the respondents but its burden was significantly greater in females (P < 0.001, 95% CI of the difference: -0.75 to -0.53). Conclusions. The findings reflect discrepancies in providing the required care for the studied Iranian patients with type 2 diabetes to prevent their disease's complications. PMID- 25140259 TI - Left ventricle pseudoaneurysm: contribution of multimodality imaging to the diagnosis. AB - The left ventricle pseudoaneurysm is an anomaly of the left ventricle and is severed and joined with a pocket look. There may be secondary to a myocardial infarction, trauma, or surgical procedure. Sometimes the cause is not found. Complications are heart failure, arrhythmias, vascular embolism, and sudden death. The treatment is surgical only. The authors report the case of a black patient of 64 years old, without medical history, had seen to a deformation of the cardiac shadow in radiography. The left ventricle pseudoaneurysm and in situ thrombus are visualized in echocardiography and CT scan. The patient is waiting for heart surgery. PMID- 25140260 TI - Novel Use of the GuideLiner Catheter to Deliver Rotational Atherectomy Burrs in Tortuous Vessels. AB - Rotational atherectomy (RA) for heavily calcified lesions is essential for improved stent delivery and stent expansion. In tortuous vessels it is often difficult to advance the burr without rotation and possible injury to the endothelium of healthy vessel. The GuideLiner catheter, a child in mother catheter, has recently been used to allow for increased support for delivery of stents through tortuous vessels. We report a novel use of the GuideLiner for the delivery of an RA burr in tortuous vessels requiring increased guide support. PMID- 25140258 TI - The interplay between reproductive social stimuli and adult olfactory bulb neurogenesis. AB - Adult neurogenesis is a striking form of structural plasticity that adapts the brain to the changing world. Accordingly, new neuron production is involved in cognitive functions, such as memory, learning, and pattern separation. Recent data in rodents indicate a close link between adult neurogenesis and reproductive social behavior. This provides a key to unravel the functional meaning of adult neurogenesis in biological relevant contexts and, in parallel, opens new perspectives to explore the way the brain is processing social stimuli. In this paper we will summarize some of the major achievements on cues and mechanisms modulating adult neurogenesis during social behaviors related to reproduction and possible role/s played by olfactory newborn neurons in this context. We will point out that newborn interneurons in the accessory olfactory bulb (AOB) represent a privileged cellular target for social stimuli that elicit reproductive behaviors and that such cues modulate adult neurogenesis at two different levels increasing both proliferation of neuronal progenitors in the germinative regions and integration of newborn neurons into functional circuits. This dual mechanism provides fresh neurons that can be involved in critical activities for the individual fitness, that is, the processing of social stimuli driving the parental behavior and partner recognition. PMID- 25140261 TI - Correction of multiple canine impactions by mixed straightwire and cantilever mechanics: a case report. AB - Background. This case report describes the orthodontic treatment of a woman, aged 17 years, with a permanent dentition, brachyfacial typology, Angle Class I, with full impaction of two canines (13,33), and a severe ectopy of the maxillary left canine. Her main compliant was the position of the ectopic teeth. Methods. Straightwire fixed appliances, together with cantilever mechanics, were used to correct the impaired occlusion and to obtain an ideal torque control. Results and Conclusion. The treatment objectives were achieved in 26 months of treatment. The impactions were fully corrected with an optimal torque. The cantilever mechanics succeeded in obtaining tooth repositioning in a short lapse of time. After treatment, the dental alignment was stable. PMID- 25140262 TI - A paradoxical triad: scapulothoracic dissociation with clavicle and humeral shaft fractures. AB - Scapulothoracic dissociation involves varying degree of discontinuity of the upper extremity from its truncal attachment. An eighteen-year-old male presented to the accident and emergency department following a motor vehicle accident where he was hit by a four wheeler while riding a two wheeler. He had tenderness and deformity over the left clavicle and the left humerus. He was unable to perform active wrist and finger dorsiflexion. A CT subsequently revealed a grade 2 splenic laceration. The splenic laceration was treated conservatively. As his general condition improved, he was gradually weaned off the ventilator and his left upper limb neurology was reassessed. He had isolated radial nerve palsy with an otherwise intact brachial plexus. He underwent internal fixation of the clavicle and the humerus. At 4 months after injury the EMG/NCV report showed signs of renervation of the radial nerve, and the fracture progressed to an uneventful union. This prior unreported triad of scapulothoracic dissociation with ipsilateral clavicular and humeral fractures may represent a parody. An apparent increase in the severity of skeletal injury was associated with a paradoxical decrease in the severity of neurovascular injury. We report this case to create awareness among orthopedic surgeons and emergency physicians about the clinical presentation of such injuries. PMID- 25140263 TI - Bicondylar hoffa fracture successfully treated with headless compression screws. AB - Bicondylar coronal plane fracture, eponymically named Hoffa fractures, is an extremely rare injury. We present a case of isolated unilateral bicondylar Hoffa fracture that was successfully treated with open reduction and internal fixation using headless compression screws with satisfactory results. We inserted posteroanteriorly oriented Acutrak screws perpendicular to the fracture plane via lateral parapatellar arthrotomy, which provided excellent compression across the fracture. PMID- 25140264 TI - Bilateral atypical femoral fractures in a patient with multiple myeloma treated with intravenous bisphosphonate therapy. AB - Bisphosphonates are currently the standard approach to managing bone disease in multiple myeloma. Bisphosphonates have high bone affinity that inhibits osteoclastic activity and additionally reduces the growth factors released from malignant or osteoblastic cells, thereby impairing abnormal bone remodeling which leads to osteolysis. However, patients of multiple myeloma may be at a higher risk of atypical femoral fractures because the treatment for malignant myeloma requires notably higher cumulative doses of bisphosphonates. Here we present a patient with bilateral atypical femoral fractures and multiple myeloma treated with intravenous bisphosphonate therapy. PMID- 25140265 TI - Pleomorphic adenomas of the parapharyngeal space. AB - Background. Parapharyngeal space is one of potential facial planes for neoplasms and infections and represents less than 1% of all head and neck tumours. Occurrence of the pleomorphic adenoma in the parapharyngeal space is a rarity. Case Presentation. Here, three giant pleomorphic adenomas of different sizes occupying the parapharyngeal space in three patients are reported. Extensive preoperative diagnostic workup was done in order to verify the nature and size of the tumour and the proximity to the large vessels. Review of the literature, clinical features, pathology, radiological findings, and treatment of these tumours are discussed. Conclusion. The excision of the tumor through submandibular transcervical approach, without cutting the mandible, turned out to be a safe and radical approach in all three cases. PMID- 25140266 TI - Tegmen tympani defect and brain herniation secondary to mastoid surgery: case presentation. AB - Brain herniation into the middle ear is very rarely seen. In addition to reasons like congenital factors, trauma, and infection, tegmen defect may develop as a result of iatrogenic events secondary to chronic otitis media surgery with or without cholesteatoma. Since it may cause life-threatening complications, patients must be evaluated and monitored for tegmen defect. In this paper, diagnosis and treatment of a brain herniation case due to iatrogenic tegmen defect were described along with relevant literature. PMID- 25140267 TI - Gitelman Syndrome in a School Boy Who Presented with Generalized Convulsion and Had a R642H/R642W Mutation in the SLC12A3 Gene. AB - An 8-year-old Japanese boy presented with a generalized convulsion. He had hypokalemia (serum K 2.4 mEq/L), hypomagnesemia, and metabolic alkalosis (BE 5.7 mmol/L). In addition, his plasma renin activity was elevated. He was tentatively diagnosed with epilepsy on the basis of the electroencephalogram findings and was treated by potassium L-aspartate and carbamazepine to control the hypokalemia and seizure, respectively. However, a year later, the patient continued to have similar abnormal laboratory data. A presumptive diagnosis of Gitelman syndrome (GS) was then made and the patient's peripheral blood mononuclear cells were subjected to sequence analysis of the SLC12A3 gene, which encodes a thiazide sensitive sodium-chloride cotransporter. The patient was found to have compound heterozygous mutations, namely, R642H inherited from his father and R642W inherited from his mother. Thus, if a patient shows persistent hypokalemia and metabolic alkalosis, GS must be considered, even if the patient exhibits atypical clinical symptoms. PMID- 25140268 TI - High-dose subcutaneous immunoglobulins for the treatment of severe treatment resistant polymyositis. AB - Polymyositis is a rare debilitating condition characterized by chronic inflammation and muscle weakness. Standard treatments include corticosteroids and immunosuppressants; however, resistance to these regimens may develop. Intravenous immunoglobulins (IVIg) are thus recommended for patients with drug resistant polymyositis. The patient presented a resistant polymyositis with severe muscle weakness, increasing dysphagia, and significant loss in weight. Subcutaneous immunoglobulins (SCIg) were initiated after failure of steroids and immunosuppressive drugs. SCIg was given twice per week (2 then 1.3 g/kg/month). Clinical recovery was observed within 2 months after the SCIg initiation. After several injections, the patient showed a progressive improvement in muscle strength. Serum creatine kinase activity decreased to normal levels, and dysphagia was resolved. The SC injections were generally well tolerated and good patient satisfaction was reported. This promising observation suggests that SCIg may be useful in active and refractory polymyositis. PMID- 25140269 TI - Giant bilateral adrenal myelolipoma with congenital adrenal hyperplasia. AB - Myelolipomas are rare and benign neoplasms, predominant of the adrenal glands, consisting of adipose and mature hematopoietic tissue, commonly discovered incidentally with increased use of radiologic imaging. Few cases of giant bilateral adrenal masses are reported, especially in the setting of congenital adrenal hyperplasia (CAH). We report the case of a 39-year-old male with a history of CAH secondary to 21-alpha hydroxylase deficiency on steroids since childhood, self-discontinued during adolescence, presenting with abdominal distension, fatigue, decreased libido, and easy bruising. Imaging revealed giant bilateral adrenal masses. He subsequently underwent bilateral adrenalectomy found to be myelolipomas measuring 30 * 25 * 20 cm on the left and weighing 4.1 kg and 25 * 20 * 13 cm on the right and weighing 2.7 kg. Adrenal myelolipomas are found to coexist with many other conditions such as Cushing's syndrome, Addison's disease, and CAH. We discuss the association with high adrenocorticotropic hormone (ACTH) states and review the studies involving ACTH as proponent leading to myelolipomas. Massive growth of these tumors, as in our case, can produce compression and hemorrhagic symptoms. We believe it is possible that self discontinuation of steroids, in the setting of CAH, may have resulted in the growth of his adrenal masses. PMID- 25140270 TI - Huge Trombus including Left Renal Vein, Ovarian Vein, and Inferior Vena Cava Mimicking Renal Colic. AB - A 31-year-old female presented with acute left flank pain; she had a C/S at the postpartum day 24. Ureteral stone was suspected but ultrasound examination was normal. Then Doppler ultrasound revealed a trombus in left renal vein and inferior vena cava. Contrast enhanced MDCT scan showed swelled and nonfunctional left kidney, a trombus including distal part of left ovarian vein, left renal vein, and inferior vena cava. We started anticoagulation treatment. Further examination revealed diagnosis of chronic myeloproliferative disease. The trombus was completely recanalized at 3-month followup. PMID- 25140271 TI - SIMPLE Technique of Laparoscopic Nephrectomy for Ectopic Nonfunctioning Pelvic Kidney Secondary to Pelviureteric Junction Obstruction: A Feasible and Safe Technique. AB - Ectopic kidneys are rare developmental anomalies. Anomalous blood supply of the pelvic ectopic kidneys poses a problem for a minimally invasive surgery. Although laparoscopic nephrectomies have been described for symptomatic nonfunctioning pelvic ectopic kidney, this is the first case report that highlights the safety and feasibility of SIMPLE technique of laparoscopic nephrectomy in a pelvic kidney. PMID- 25140272 TI - A case of the nutcracker syndrome developed after delivery. AB - We report a case of nutcracker syndrome that developed after delivery. A 32-year old woman visited our clinic complaining of gross hematuria 4 months after delivery. Urethrocystoscopic examination failed to show hematuria coming from the ureteral orifice; however, enhanced computed tomography revealed the compression of the left renal vein between the aorta and superior mesenteric artery. Therefore, we diagnosed her with nutcracker syndrome and conservatively observed her. The macrohematuria disappeared by itself after 1 month. This is the first report to describe a case of nutcracker syndrome that developed after delivery. PMID- 25140273 TI - Spontaneous postmenopausal urethral prolapse treated surgically and successfully. AB - Urethral prolapse (UP) is a circular complete eversion of the distal urethral mucosa through the external meatus. It is a rare condition seen mostly in African American premenarcheal girls. Both a medical and a surgical approach to this condition have been described. We present a case of a spontaneous urethral prolapse in a 60-year-old postmenopausal Caucasian woman, who failed medical management and underwent successful surgical management. The patient is asymptomatic 18 months following the procedure. PMID- 25140274 TI - Fahr syndrome unknown complication: overactive bladder. AB - A 38-year-old male patient was admitted to our outpatient department because of frequency and urgency incontinence. During evaluation it was detected that the patient was suffering from frequency which was progressive for one year, feeling of incontinence, and urgency incontinence. There was no urologic pathology detected in patient's medical and family history. Neurologic consultation was requested due to his history of boredom, reluctance to do business, balance disorders, and recession for about 3 years. Brain computerized tomography (CT) scan revealed that amorphous calcifications were detected in the bilaterally centrum semiovale, basal ganglia, capsula interna, thalami, mesencephalon, pons and bulbus, and the bilateral cerebellar hemispheres. We have detected spontaneous neurogenic detrusor overactivity without sphincter dyssynergia after evaluating the voiding diary, cystometry, and pressure flow study. We consider the detrusor overactivity which occurred one year after the start of the neurological symptoms as the suprapontine inhibition and damage in the axonal pathways in the Fahr syndrome. PMID- 25140275 TI - How aortic stiffness in postmenopausal women is related to common cardiovascular risk factors. AB - Objective. Our study investigates major common cardiovascular risk factors relation with aortic stiffness on 269 postmenopausal women by global pulse wave velocity (PWVg), useful to relate PWVg to risk of major cardiovascular events. Patients and Methods. Women were categorized as hypertensive (H), hypercholesterolemic (C), or diabetic (D). Aortic stiffness was assessed by PWVg measured with pulsed Doppler, at the left ventricular outflow tract (LVOT) and at the right common femoral artery. Results. All population mean PWVg was 8.2 m/s. 85 (26.5%) women were H; mean PWVg was 7.9 m/s. HC women were 118 (36.7%), with mean PWVg 8.3 m/s. HD women were 30 (9.5%), with mean PWVg 7.8 m/s. HDC women were 36 (11.2%), with mean PWVg 9.3 m/s. 52 (16.1%) menstruate women without risk factor were control group (CG), with mean PWVg 6.5 m/s. Highly significant was the statistical difference in PWVg between HDC women and each other group: P < 0.0005 versus CG; P < 0.01 versus H; P < 0.03 versus HC, and P < 0.05 versus HD. No difference in PWG was observed comparing the other groups. There was difference for age among all groups, except for CG, made by younger women. Conclusion. PWVg was highly increased in postmenopausal women affected by hypertension, diabetes, and hypercholesterolemia all at once. Hypertension is the major determinant for PWVg. The only addition of diabetes or hypercholesterolemia did not increase significantly PWVg. Our study supports the usefulness of the assessment of aortic stiffness as a marker of cardiovascular disease. PMID- 25140276 TI - Automated system for kinetic analysis of particle size distributions for pharmaceutically relevant systems. AB - Detailing the kinetics of particle formation for pharmaceutically relevant solutions is challenging, especially when considering the combination of formulations, containers, and timescales of clinical importance. This paper describes a method for using commercial software Automate with a stream-selector valve capable of sampling container solutions from within an environmental chamber. The tool was built to monitor changes in particle size distributions via instrumental particle counters but can be adapted to other solution-based sensors. The tool and methodology were demonstrated to be highly effective for measuring dynamic changes in emulsion globule distributions as a function of storage and mixing conditions important for parenteral nutrition. Higher levels of agitation induced the fastest growth of large globules (>=5 MUm) while the gentler conditions actually showed a decrease in the number of these large globules. The same methodology recorded calcium phosphate precipitation kinetics as a function of [Ca(2+)] and pH. This automated system is readily adaptable to a wide range of pharmaceutically relevant systems where the particle size is expected to vary with time. This instrumentation can dramatically reduce the time and resources needed to probe complex formulation issues while providing new insights for monitoring the kinetics as a function of key variables. PMID- 25140277 TI - Relationship between Nutrition Knowledge and Physical Fitness in Semiprofessional Soccer Players. AB - Whereas nutrition has a crucial role on sport performance, it is not clear to what extent nutrition knowledge is associated with physical fitness. The aim of this study was to examine the current level of nutrition knowledge of soccer players and whether this level is associated with physical fitness. Soccer players (n = 185, aged 21.3 +/- 4.9 yr, weight 72.3 +/- 8.4 kg, and height 177.5 +/- 6.4 cm) performed a battery of physical fitness tests (sit-and-reach test, SAR; physical working capacity in heart rate 170, PWC170; and Wingate anaerobic test, WAnT) and completed an 11-item nutrition knowledge questionnaire (NKQ). Low to moderate Pearson correlations (0.15 < r < 0.34, p < 0.05) of NKQ with age, weight, height, fat free mass (FFM), SAR, peak power, and mean power of WAnT were observed. Soccer players with high score in NKQ were older (4.4 yr (2.2; 6.6), mean difference (95% confidence intervals)) and heavier (4.5 kg (0.6; 8.3)) with higher FFM (4.0 kg (1.1; 6.8)) and peak power (59 W (2; 116)) than their counterparts with low score. The moderate score in the NKQ suggests that soccer players should be targeted for nutrition education. Although the association between NKQ and physical fitness was low to moderate, there were indications that better nutrition knowledge might result in higher physical fitness and, consequently, soccer performance. PMID- 25140278 TI - Understanding thoracic outlet syndrome. AB - The diagnosis of thoracic outlet syndrome was once debated in the world of vascular surgery. Today, it is more understood and surprisingly less infrequent than once thought. Thoracic outlet syndrome (TOS) is composed of three types: neurogenic, venous, and arterial. Each type is in distinction to the others when considering patient presentation and diagnosis. Remarkable advances have been made in surgical approach, physical therapy, and rehabilitation of these patients. Dedicated centers of excellence with multidisciplinary teams have been developed and continue to lead the way in future research. PMID- 25140279 TI - The value of neuromonitoring in cervical spine surgery. PMID- 25140281 TI - "From writing illegibly to composing fiction: The story of a blind man with 20/20 vision". PMID- 25140280 TI - Case comparison and literature review of glioblastoma: A tale of two tumors. AB - BACKGROUND: Diagnosis of glioblastoma multiforme (GBM) includes a heterogeneous group of tumors. We describe two cases with histopathologically and molecularly similar tumors, but very different outcomes. We attempt to illustrate the need for improved prognostic markers for GBM. CASE DESCRIPTION: Two patients with similar molecular profiles were retrospectively identified. The following markers were assessed: O (6)-methylguanine DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) 1 and 2 status, epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) status, Ki-67, p53, and 1p/19q status. Each patient was assigned a Karnofsky performance score at presentation. Case 1 (62-year-old male) was a right temporal lobe glioblastoma with a molecular profile of amplified EGFR, normal PTEN, no IDH1/2 mutation, 28.7% MGMT promoter methylation, 5-20% Ki-67, 1p deletion, and 19q intact. The patient underwent resection followed by radiation therapy and 2 years of chemotherapy, and was asymptomatic and tumor free 5 years post diagnosis. Tumor eventually recurred and the patient expired 72 months after initial diagnosis. Case 2 (63-year-old male) was a right frontal white matter mass consistent with glioblastoma with a molecular profile of amplified EGFR, absent PTEN, no IDH1/2 mutation, 9.9% MGMT promoter methylation, 5-10% Ki-67, and 1p/19q status inconclusive. A radical subtotal resection was performed; however, 2 weeks later symptoms had returned. Subsequent imaging revealed a tumor larger than at diagnosis. The patient expired 3 months after initial diagnosis. CONCLUSION: The need for formulating more robust means to classify GBM tumor subtypes is paramount. Standard histopathologic and molecular analyses are costly and did not provide either of these patients with a realistic appraisal of their prognosis. Individualized whole genome testing similar to that being reported for medulloblastoma and other tumors may be preferable to the array of tests as currently utilized. PMID- 25140282 TI - Johannes Vermeer of Delft [1632-1675] and vision in neuroendoscopy. AB - BACKGROUND: Johannes Vermeer of Delft [1632-1675] was one of the greatest Masters of the Dutch Golden Age who was intensely preoccupied with the behavior of light and other optical effects and was entitled "The Master of Light". He fastidiously attended to the subtleties of visual expression through geometry, composition, and precise mastery of the rules of perspective. It has been our impression that some visual similarity does exist between neuroendoscopic images and some of Vermeer's paintings. Such a relation could be explained by the fact that optical devices are utilized in producing both types of display. METHODS: We reviewed the pertinent medical and art literature, observed some video clips of our endoscopy cases, and inspected digital high resolution images of Vermeer's paintings in order to elaborate on shared optical phenomena between neuroendoscopic views and Vermeer's paintings. RESULTS: Specific optical phenomena are indeed shared by Johannes Vermeer's works and neuroendoscopic vision, namely light and color effects as well as the rules of perspective. CONCLUSION: From the physical point of view, the possibility that a camera obscura inspired Vermeer's artistic creation makes the existence of a visual link between his paintings and the endoscopic views of the intracranial cavity comprehensible. PMID- 25140283 TI - Colloid cysts posterior and anterior to the foramen of Monro: Anatomical features and implications for endoscopic excision. AB - BACKGROUND: Colloid cysts are usually located at the rostral part of the third ventricle in proximity to the foramina of Monro. Some third ventricular colloid cysts, however, attain large sizes, reach a very high distance above the roof of the third ventricle, and pose some challenges during endoscopic excision. These features led to the speculation that for such a pattern of growth to take place, the points of origin of these cysts should be at areas away from the foramina of Monro at which some anatomical "windows" exist that are devoid of compact, closely apposed forniceal structures. METHODS: A review of the literature on anatomical variations of the structures in the vicinity of the roof of the third ventricle and on reported cases with similar features was conducted. RESULTS: Colloid cysts may grow vertically up past the roof of the third ventricle through anatomical windows devoid of the mechanical restraint of the forniceal structures. CONCLUSION: Some anatomical variations of the forniceal structures may allow unusually large sizes and superior vector of growth of a retro- or post foraminal colloid cyst. Careful preoperative planning and knowledge of the pertinent pathoanatomy of these cysts before endoscopic excision is very important to avoid complications. PMID- 25140284 TI - Angio negative spontaneous subarachnoid hemorrhage: Is repeat angiogram required in all cases? AB - BACKGROUND: In some cases of spontaneous subarachnoid hemorrhage (SAH), the cause of bleed remains obscure on initial evaluation. These patients may harbor structural lesions. We aim to determine the utility of repeat angiogram in these subsets of patients. METHODS: In this prospective study, patients with SAH with a negative computed tomographic angiogram (CTA) and digital subtraction angiogram (DSA) were included. A repeat angiogram was done after 6 weeks of initial angiogram. Patients were divided into perimesencephalic SAH (PM-SAH) and diffuse classic SAH (Classic-SAH) groups. Outcome was determined by modified Rankin score (mRS). RESULTS: A total of 22% (39/178) of all SAH were angio-negative. A total of 90% (n = 35) of these were in Hunt and Hess grade 1-3. A total of 22 patients had PM-SAH and 17 had a Classic-SAH. Repeat angiogram did not reveal any pathology in the PM-SAH group, whereas two patients with Classic-SAH were found to have aneurysms. At 6 months follow-up, 95% patients of PM-SAH and 83.3% of Classic-SAH had mRS of 0. CONCLUSION: Repeat angiogram is probably not necessary in patients of PM-SAH and they tend to have better outcome. Classic-SAH pattern of bleed is associated with fair chances of an underlying pathology and a repeat angiogram is recommended and these cases and they have poorer outcome. PMID- 25140285 TI - Giant asymptomatic mastoid pneumocele producing a scalp swelling: A rare case report. AB - BACKGROUND: Intraosseous collections of air are rare in comparison to the extra osseous collection. Pneumoceles are rare entities defined as enlarged pneumatized air sinuses or air cells, with focal or diffuse thinning of the surrounding bony walls. They may affect mastoid air cells and any of the paranasal sinuses. CASE DESCRIPTION: We report a rare case of extensive mastoid pneumatisation in a young male patient. Patient was completely asymptomatic with swelling as the main complaint. Short history of development raised suspicion for a malignant lesion. Cholesteatoma was also taken as a differential diagnosis. However, computed tomography (CT) scan showed gross expansion of mastoid air cells with no lesion inside it. The walls of mastoid were markedly thinned out, making the diagnosis as pneumocele. In spite of a large swelling, conservative treatment was adopted in view of no symptoms and was advised follow-up regularly to detect any possible complications. CONCLUSION: Our case was interesting in that rare mastoid pneumoceles can be totally asymptomatic and can be large enough to raise concern for a malignant lesion. Literature shows that such mastoid pneumocele are symptomatic and require active intervention. Our asymptomatic mastoid pneumocele is a rare instance requiring no surgical procedure and was followed-up. Overall, such lesions should be treated as normal variants of physiological mastoid. PMID- 25140286 TI - Complete resolution of steroid-resistant organizing pneumonia associated with myelodysplastic syndrome following allogeneic hematopoietic cell transplantation. AB - Pulmonary complications in patients with hematological malignancies are often caused by infection but are sometimes associated with an underlying disease such as organizing pneumonia (OP). Here, we report a case of life-threatening steroid resistant OP associated with myelodysplastic syndrome (MDS) and successfully performed allogeneic hematopoietic cell transplantation (HSCT). A 33-year-old female with refractory anemia with excess blasts-1 that had progressed from refractory anemia with ringed sideroblasts and concomitant Sweet's syndrome was admitted. Multiple pulmonary infiltrates were revealed on a chest computed tomography scan, which progressively worsened even after chemotherapy and corticosteroid therapy. No evidence of infection was observed in bronchoalveolar lavage fluid. A histological examination of a transbronchial lung biopsy specimen showed lymphocyte invasion with fibrosis, indicating that the pulmonary infiltrates were OP associated with MDS. Before transplantation, she suffered from respiratory failure and required oxygen supplementation. She developed idiopathic pneumonitis syndrome on day 61 that responded well to corticosteroid therapy, and the OP pulmonary infiltrates improved gradually after HSCT, She was discharged on day 104 and is well without recurrence of OP or MDS 2 years after HSCT. PMID- 25140288 TI - Design of static synchronous series compensator based damping controller employing invasive weed optimization algorithm. AB - This paper proposes designing of Static Synchronous Series Compensator (SSSC) based damping controller to enhance the stability of a Single Machine Infinite Bus (SMIB) system by means of Invasive Weed Optimization (IWO) technique. Conventional PI controller is used as the SSSC damping controller which takes rotor speed deviation as the input. The damping controller parameters are tuned based on time integral of absolute error based cost function using IWO. Performance of IWO based controller is compared to that of Particle Swarm Optimization (PSO) based controller. Time domain based simulation results are presented and performance of the controllers under different loading conditions and fault scenarios is studied in order to illustrate the effectiveness of the IWO based design approach. PMID- 25140287 TI - Development of a novel cellular model of Alzheimer's disease utilizing neurosphere cultures derived from B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J embryonic mouse brain. AB - Increased production, oligomerization and aggregation of amyloid-beta (Abeta) peptides are hallmark pathologies of Alzheimer's disease (AD). Expressing familial AD mutations (amyloid precursor protein and/or presenilins mutations), the Abeta-pathologies of AD has been recapitulated in animal models of AD. Very few primary cell culture-based models of AD are available and they exhibit very weak Abeta-pathologies compared to what is seen in AD patients and animal models of AD. CNS stem/progenitor cells are present in both embryonic and adult brains. They can be isolated, grown as neurospheres and differentiated into neurons, astrocytes and oligodendrocytes. It is not yet known whether CNS stem/progenitor cells can support the production of Abeta peptides in culture. In this report, we have established Abeta-pathologies such as production, secretion, oligomerization and aggregation of Abeta peptides utilizing neurosphere cultures to create a new cellular model of AD. These cultures were developed from E15 embryonic brains of transgenic mice carrying the Swedish mutations in humanized mouse APP cDNA and the exon-9 deleted human presenilin 1 cDNA both regulated by mouse prion protein gene (Prnp) promoter. Results demonstrated the expression of transgene transcripts, APPswe protein and its processed products only in transgene positive neurosphere cultures. These cultures generate and secrete both Abeta40 and Abeta42 peptides into culture medium at levels comparable to the Abeta load in the brain of AD patients and animal models of AD, and produce pathogenic oligomers of Abeta peptides. The Abeta42/Abeta40 ratio in the medium of transgene positive neurosphere cultures is higher than any known cellular models of AD. Conformation dependent immunocytochemistry demonstrated the possible presence of intracellular and extracellular aggregation of Abeta peptides in neurosphere cultures, which are also seen in AD brain and animal models of AD. Collectively, our neurosphere cultures provide robust Abeta-pathologies of AD better than existing cellular model of Alzheimer's disease. PMID- 25140289 TI - Third degree formic acid chemical burn in the treatment of a hand wart: a case report and review of the literature. AB - OBJECTIVE: Cutaneous warts are very common and a large variety of topical treatments and drugs can be employed to cure these skin injuries that can arise on any part of the body. But are these products really safe? METHOD: We performed a case description and PubMed literature review using key words "wart," "chemical burn," and "formic acid." All articles in English and French were selected. RESULTS: This is the first report of a chemical burn by formic acid in the treatment of warts. Numerous topical treatments for cutaneous warts are available with many new drugs appearing every year. However, only a few treatments have proven their effectiveness, such as salicylic acid or cryotherapy with liquid nitrogen that are commonly used. Moreover, most cutaneous warts will resolve spontaneously without any treatment and several products, including topical acids and cryotherapy devices, presented adverse effects such as chemical burns or frostbites so demonstrating that even frequently used treatments can be harmful. CONCLUSION: Topical treatments used for wart removal are not without risk even if some products are sold without prescription. For self-treatment products, we recommend enhanced warning by the pharmacist about the risks involved. PMID- 25140290 TI - Medication in nursing homes in Alsace: a preferential list of drugs obtained by consensus. AB - ABSTRACT: In order to improve patient care, OMEDIT (Observatory of drugs, medical devices and therapeutic innovation) Alsace, conducted a study to develop a Preferential list of Drugs adapted to the Elderly (PDE list) in nursing homes. The study conducted from December 2011 to June 2012 was organized in 4 phases: 1) creation of a preliminary list of drugs from those currently used in nursing homes in Alsace, 2) application of a two-round Delphi process to evaluate the preliminary list involving mobilization of experts from different backgrounds (geriatricians, general practitioners, pharmacists ...), 3) identification of molecules considered in literature as potentially inappropriate, 4) generation of a final PDE list, including information concerning proper use of drugs for prescription and administration. 53 experts participated in the study. In the first round, 338 drugs were on the preliminary list, 246 were considered as appropriate by experts and 28 as inappropriate. 64 drugs without consensus were submitted to a second round. 32 of them were considered as inappropriate and 32 others remained on the list with no consensus. These last 32 were evaluated by OMEDIT and 3 were considered as appropriate drugs for the elderly. Totally, 252 drugs constitute the final PDE list from our study. The PDE list constitutes a new guide for optimization of both prescription and administration of drugs in nursing homes and could help reduce misuses and poly-medication, which are constant preoccupations to avoid adverse drug reactions in elderly. KEY POINTS: ? The study was carried out with the aim to create a Preferential list of Drugs adapted to the Elderly (PDE list) in nursing homes using a modified Delphi method. ? The PDE list constitutes a new guideline to harmonize practices in nursing homes and to help physicians and nurses to achieve best possible care management. PMID- 25140291 TI - Pneumococcal-meningitis associated acute disseminated encephalomyelitis (ADEM) - case report of effective early immunotherapy. AB - INTRODUCTION: Unvaccinated patients with history of splenectomy are prone to fulminant courses of Streptococcus pneumoniae-associated bacterial meningitis. Besides direct brain damage those patients may additionally suffer from parainfectious syndromes, notably vasculitis and acute disseminated encephalomyelitis (ADEM). Differentiation and treatment of these immunological reactions is challenging. METHODS: Case report. RESULTS: A 61 year-old woman with history of splenectomy without vaccination for S. pneumoniae presented with progressive headache and meningism. CSF-analysis revealed pleocytosis with microbiological evidence for pneumococcal meningitis. After unsuspicious initial cranial CT imaging and initiation of appropriate antibiotic therapy, MRI two days later showed widespread FLAIR- and T2-hyperintense white matter lesions that further progressed upon follow-up MRI and that fulfilled imaging criteria of ADEM. Meanwhile the patient deteriorated and required mechanical ventilation. Cranial angiography showed no signs of vasculitis or vasospasms. Screening for autoimmune diseases remained negative, however oligoclonal bands turned positive. Brain biopsy mainly revealed perivascular CD4+ T-cells and demyelinated areas. Despite ongoing acute meningitis, a 10-day corticosteroid-pulse was initiated followed by steroid-tapering. Within 4 weeks, clinical and MRI findings ameliorated. In an one-year follow-up visit, the patient significantly recovered, MRI lesions were markedly reduced and no further relapses occurred. CONCLUSION: Acute pneumococcal meningitis in unvaccinated splenectomized patients may be complicated by a monophasic course of parainfectious ADEM that can be controlled with high-dose corticosteroids. Parainfectious vasculitis or cerebritis are important differential diagnoses and exact differentiation of these entities is important to initiate early appropriate immunotherapy. PMID- 25140292 TI - The influence of race/ethnicity and place of service on breast reconstruction for Medicare beneficiaries with mastectomy. AB - Racial disparities in breast reconstruction for breast cancer are documented. Place of service has contributed to disparities in cancer care; but the interaction of race/ethnicity and place of service has not been explicitly examined. We examined whether place of service modified the effect of race/ethnicity on receipt of reconstruction. We included women with a mastectomy for incident breast cancer in SEER-Medicare from 2005-2009. Using Medicare claims, we determined breast reconstruction within 6 months. Facility characteristics included: rural/urban location, teaching status, NCI Cancer Center designation, cooperative oncology group membership, Disproportionate Share Hospital (DSH) status, and breast surgery volume. Using multivariable logistic regression, we analyzed reconstruction in relation to minority status and facility characteristics. Of the 17,958 women, 14.2% were racial/ethnic women of color and a total of 9.3% had reconstruction. Caucasians disproportionately received care at non-teaching hospitals (53% v. 42%) and did not at Disproportionate Share Hospitals (77% v. 86%). Women of color had 55% lower odds of reconstruction than Caucasians (OR = 0.45; 95% CI 0.37-0.55). Those in lower median income areas had lower odds of receiving reconstruction, regardless of race/ethnicity. Odds of reconstruction reduced at rural, non-teaching and cooperative oncology group hospitals, and lower surgery volume facilities. Facility effects on odds of reconstruction were similar in analyses stratified by race/ethnicity status. Race/ethnicity and facility characteristics have independent effects on utilization of breast reconstruction, with no significant interaction. This suggests that, regardless of a woman's race/ethnicity, the place of service influences the likelihood of reconstruction. PMID- 25140293 TI - Synergistic antitumor effects of S-1 with eribulin in vitro and in vivo for triple-negative breast cancer cell lines. AB - Triple-negative breast cancer (TNBC) is associated with a higher incidence of recurrence and distant metastasis and a poor prognosis, whereas effective treatment strategies remain to be established. Finding an effective treatment for TNBC has become imperative. We examined the effect of the combination of S-1 (or 5-FU in an in vitro study) and eribulin in TNBC cell lines. The in vitro effect of the combination was examined in four TNBC cell lines (MDA-MB-231, MDA-MB-468, BT-549 and MX-1) using a combination index and isobolograms. In addition, we assessed the effect of the combination in an MDA-MB-231 tumor xenograft model. A synergistic effect was observed in three TNBC cell lines (MDA-MB-231, MDA-MB-468, and MX-1), and in an in vivo study, the combination of S-1 and eribulin resulted in significantly higher antitumor effects compared with S-1 or eribulin alone. 5 FU induced epithelial-mesenchymal transition (EMT) change in the TNCB cell line, as supported by the decreased expression of epithelial marker and the increased expression of mesenchymal markers. Meanwhile, TGF-beta induced EMT changes in a TNBC cell line and decreased the sensitivity to 5-FU. This result suggests that 5 FU-induced EMT changes reduce the sensitivity to 5-FU. In contrast, eribulin induced a mesenchymal-epithelial transition (MET) in a TNBC cell line. The EMT phenotype induced by 5-FU was also canceled by eribulin. We demonstrate that the combination of S-1 (5-FU) and eribulin exerts a synergistic effect for TNBC cell lines through MET-induction by eribulin. Therefore, this combination therapy may be a potential treatment option for TNBC. PMID- 25140294 TI - Comparison of generalist predators in winter-flooded and conventionally managed rice paddies and identification of their limiting factors. AB - Winter-flooding of rice paddies without the application of agricultural chemicals is attracting attention as a new agricultural method for enhancing the habitat conditions of wintering waterfowl in rice paddy ecosystems throughout Japan and east Asia. Conditions in these paddies are expected to result in restoration of not only the winter habitats of waterfowl but also those of other taxonomic groups during the rice growing season. In this study, we tested whether the diversity of summer spiders--ubiquitous predators in rice paddies--was higher in the winter-flooded paddies than in the conventional ones by conducting field measurements in 31 winter-flooded and 7 conventional paddies. Limiting factors of spiders in the winter-flooded paddies were then examined. Results revealed that both the density and species richness of spiders were significantly higher in the winter-flooded paddies than in the conventional ones both before and after the insecticide application against pecky rice bug Stenotus rubrovittatus (Matsumura)(Hemiptera: Miridae) to conventional paddies. In addition, spider density and species richness in the winter-flooded paddies correlated with the availability of two prey groups--chironomids and other nematocera. These findings suggest that in the winter-flooded paddies the diversity of generalist predators is higher than in the conventional ones during the rice-growing season and that the combination of management at both the landscape and field level is likely more effective for increasing spider abundance in winter-flooded paddies. PMID- 25140295 TI - Trimodality therapy for bladder preservation in the elderly population with invasive bladder cancer. AB - Bladder cancer is considered as primarily a disease of the elderly, typically aged in their 70s or 80s and often with associated medical comorbidities. Unfortunately, fewer elderly patients receive radical treatment for muscle invasive bladder cancer (MIBC) that their younger counterparts. Over the last decades, several studies have shown that the use of trimodality therapy consisting of transurethral bladder resection followed by concomitant chemotherapy and radiation therapy results in comparable outcomes to radical cystectomy, considered the gold standard for this disease. In this review, we revised the literature on bladder-preservation treatments using the trimodality approach in the elderly population with MIBC. PMID- 25140296 TI - Use of an interactive, faith-based kiosk by congregants of four predominantly, african-american churches in a metropolitan area. AB - Chronic diseases are prevalent in ethnic communities. Churches represent a potent resource for targeted health promotion. A faith-based kiosk was developed as an informational tool and placed in four predominantly (>80%) African-American churches. Congregants were surveyed to describe kiosk-use, kiosk-user characteristics, health status, and self-reported behavior changes attributed to the kiosk. We analyzed 1,573 questionnaires. Mean age of respondents was 46.4 years and >70% were women. "Older" congregations (mean age >=46.1 years) had more reports of diabetes (p = 0.002) and heart diseases (p = 0.01) than younger churches (mean age <=44.1), whereas asthma was more prevalent in the latter (p < 0.001). Prevalence of obesity (40%) was similar across churches (p = 0.570). Kiosk-use was reported by 420 (26.7%) respondents. Compared to non-users, kiosk users were >40 years (p < 0.001), and reported >two health conditions, adjusted Odds Ratio (95% Confidence Interval) = 1.43 (1.0-2.0), p = 0.05. Male kiosk-users preferred to select disease-specific content, aOR = 1.87 (1.10-3.17), p = 0.02, while females tended to select information about supportive community resources, aOR = 0.49 (0.23-1.04), p = 0.062. Knowledge of kiosk-user characteristics and the "health status" of a congregation, provide an opportunity for targeted, church-based health promotion. PMID- 25140297 TI - Self-Medication Practices among a Sample of Latino Migrant Workers in South Florida. AB - INTRODUCTION: Although the literature on self-medication among Latino migrant workers (LMWs) is sparse, a few existing studies indicate that this practice is common in this community. The purpose of this paper is to estimate health status, access to health care, and patterns of self-medication practices of a cohort of LMWs in South Florida. METHODS: A stratified network-based sample was utilized to recruit 278 LMWs in the Homestead area. After screening for eligibility, participants were administered a structured questionnaire that collected data on their health status, access to health care services, and self-medication practices. A convenience sample of 24 LMWs, who participated in the parent study were invited back to participate in 3 focus groups to look more in depth into self-medication practices in the LMW community. RESULTS: Study findings indicate that LMWs are affected by a vast array of health problems yet lack access to health care services. Participants already engaged in self-medication practices in the countries of origin and, upon their arrival in the US, these practices continue and, in many cases, increase. CONCLUSION: Long-held traditions and lack of access to the formal health care system in the US contribute to the high prevalence of self-medication among LMWs. Self-medication practices such as the use of prescription medications without a prescription and lay injection are high risk practices that can have harmful consequences. Prevention interventions that address self-medication in the LMW community are likely to be most effective if they are culturally adapted to the community and facilitate access to health care services. PMID- 25140298 TI - Principals, Agents, and the Intersection between Scientists and Policy-Makers: Reflections on the H5N1 Controversy. PMID- 25140299 TI - Dual-use research as a wicked problem. PMID- 25140300 TI - Absolute quantitation of post-translational modifications. PMID- 25140301 TI - Compositional Constraint Is the Key Force in Shaping Codon Usage Bias in Hemagglutinin Gene in H1N1 Subtype of Influenza A Virus. AB - It is vital to unravel the codon usage bias in order to gain insights into the evolutionary forces dictating the viral evolution process. Influenza A virus has attracted attention of many investigators over the years due to high mutation rate and being cross-specific shift operational in the viral genome. Several authors have reported that the codon usage bias is low in influenza A viruses, citing mutational pressure as the decisive force shaping up the codon usage in these viruses. In this study, complete coding sequences of hemagglutinin genes for H1N1 subtype of influenza A virus have been explored for the possible codon usage bias acting upon these genes. The results indicate overall low bias with peaking ENC values. The GC content is found to be substantially low as against AT content in the silent codon sites. Significant correlations were observed in between the compositional parameters versus AT3, implying the possible role of the latter in shaping codon usage profile in the viral hemagglutinin. The data showed conspicuously that the sequences were A redundant with most codons preferring nucleotide A over others in the third synonymous codon site. The results indicated the pivotal role of compositional pressure affecting codon usage in this virus. PMID- 25140303 TI - delta-Tocotrienol oxazine derivative antagonizes mammary tumor cell compensatory response to CoCl2-induced hypoxia. AB - In response to low oxygen supply, cancer cells elevate production of HIF-1alpha, a hypoxia-inducible transcription factor that subsequently acts to stimulate blood vessel formation and promote survival. Studies were conducted to determine the role of delta-tocotrienol and a semisynthetic delta-tocotrienol oxazine derivative, compound 44, on +SA mammary tumor cell hypoxic response. Treatment with 150 uM CoCl2 induced a hypoxic response in +SA mammary tumor cells as evidenced by a large increase in HIF-1alpha levels, and combined treatment with compound 44 attenuated this response. CoCl2-induced hypoxia was also associated with a large increase in Akt/mTOR signaling, activation of downstream targets p70S6K and eIF-4E1, and a significant increase in VEGF production, and combined treatment with compound 44 blocked this response. Additional in vivo studies showed that intralesional treatment with compound 44 in BALB/c mice bearing +SA mammary tumors significantly decreased the levels of HIF-1alpha, and this effect was associated with a corresponding decrease in Akt/mTOR signaling and activation of downstream targets p70S6 kinase and eIF-4E1. These findings demonstrate that treatment with the delta-tocotrienol oxazine derivative, compound 44, significantly attenuates +SA mammary tumor cell compensatory responses to hypoxia and suggests that this compound may provide benefit in the treatment of rapidly growing solid breast tumors. PMID- 25140304 TI - Apocynin, a low molecular oral treatment for neurodegenerative disease. AB - Accumulating evidence suggests that inflammatory mediators secreted by activated resident or infiltrated innate immune cells have a significant impact on the pathogenesis of neurodegenerative diseases. This may imply that patients affected by a neurodegenerative disease may benefit from treatment with selective inhibitors of innate immune activity. Here we review the therapeutic potential of apocynin, an essentially nontoxic phenolic compound isolated from the medicinal plant Jatropha multifida. Apocynin is a selective inhibitor of the phagocyte NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low dose. PMID- 25140302 TI - The motile breast cancer phenotype roles of proteoglycans/glycosaminoglycans. AB - The consecutive stages of cancer growth and dissemination are obligatorily perpetrated through specific interactions of the tumor cells with their microenvironment. Importantly, cell-associated and tumor microenvironment glycosaminoglycans (GAGs)/proteoglycan (PG) content and distribution are markedly altered during tumor pathogenesis and progression. GAGs and PGs perform multiple functions in specific stages of the metastatic cascade due to their defined structure and ability to interact with both ligands and receptors regulating cancer pathogenesis. Thus, GAGs/PGs may modulate downstream signaling of key cellular mediators including insulin growth factor receptor (IGFR), epidermal growth factor receptor (EGFR), estrogen receptors (ERs), or Wnt members. In the present review we will focus on breast cancer motility in correlation with their GAG/PG content and critically discuss mechanisms involved. Furthermore, new approaches involving GAGs/PGs as potential prognostic/diagnostic markers or as therapeutic agents for cancer-related pathologies are being proposed. PMID- 25140305 TI - The antileukemia activity of natural product HQ17(3) is possibly associated with downregulation of miR-17-92 cluster. AB - The compound 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)] was purified from the sap of the lacquer tree Rhus succedanea. HQ17(3) has cytotoxic effect on cancer cells and can inhibit topoisomerase (topo) IIalpha activity. We treated various cancer cells with different doses of HQ17(3) and found that leukemia cells were most sensitive to HQ17(3). After analysis of microRNA (miRNA) profiling, we found that treatment with HQ17(3) caused downregulation of miR-17 92 cluster in some leukemia cells. These changes partially restored the normal levels from leukemia-specific miRNA expression signature. Messenger RNAs of tumor suppressor proteins, such as pRB, PTEN, and Dicer, are targets of miR-17-92 cluster. Their protein levels were increased after the treatment. c-Myc is a regulatory protein for miR-17-92 gene. Similar to topo IIalpha, we found that c Myc decreased its activity after the HQ17(3) treatment, which may explain the downregulation of miR-17-92 cluster. Combined with 5-fluorouracil, NaAsO2, or ABT 737, HQ17(3) elicited additive inhibitory effects on leukemia cells. In conclusion, the high sensitivity of leukemia cells to HQ17(3) may be associated with the reduction of topo IIalpha and c-Myc activities, as well as with the downregulation of the miR-17-92 cluster expression. PMID- 25140307 TI - Angiotensin I-converting enzyme inhibitor derived from cross-linked oyster protein. AB - Following cross-linking by microbial transglutaminase, modified oyster proteins were hydrolyzed to improve inhibitory activity against angiotensin-converting enzyme (ACE) inhibitory activity with the use of a single protease, or a combination of six proteases. The oyster hydrolysate with the lowest 50% ACE inhibitory concentration (IC50) of 0.40 mg/mL was obtained by two-step hydrolysis of the cross-linked oyster protein using Protamex and Neutrase. Five ACE inhibitory peptides were purified from the oyster hydrolysate using a multistep chromatographic procedure comprised of ion-exchange, size exclusion, and reversed phase liquid chromatography. Their sequences were identified as TAY, VK, KY, FYN, and YA, using automated Edman degradation and mass spectrometry. These peptides were synthesized, and their IC50 values were measured to be 16.7, 29.0, 51.5, 68.2, and 93.9 MUM, respectively. Toxicity of the peptides on the HepG2 cell line was not detected. The oyster hydrolysate also significantly decreased the systolic blood pressure of spontaneously hypertensive rats (SHR). The antihypertensive effect of the oyster hydrolysate on SHR was rapid and long lasting, compared to commercially obtained sardine hydrolysate. These results suggest that the oyster hydrolysate could be a source of effective nutraceuticals against hypertension. PMID- 25140306 TI - The nonglycemic actions of dipeptidyl peptidase-4 inhibitors. AB - A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4), cleaves dipeptide from peptides containing proline or alanine in the N-terminal penultimate position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), enhance meal-stimulated insulin secretion from pancreatic beta-cells, but are inactivated by DPP-4. Diabetes and hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4 inhibitor, a new class of antidiabetic agents, may have pleiotropic effects. Studies have shown that DPP-4 itself is involved in the inflammatory signaling pathway, the stimulation of vascular smooth cell proliferation, and the stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates these pathophysiologic processes and has been shown to have cardiovascular protective effects in both in vitro and in vivo experiments. However, in recent randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with type 2 diabetes did not show cardiovascular protective effects. Some concerns on the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y mediated vascular responses. Further studies are required to fully characterize the cardiovascular effects of DPP-4 inhibitor. PMID- 25140309 TI - Implementation of incident learning in the safety and quality management of radiotherapy: the primary experience in a new established program with advanced technology. AB - OBJECTIVE: To explore the implementation of incident learning for quality management of radiotherapy in a new established radiotherapy program. MATERIALS AND METHODS: With reference to the consensus recommendations by American Association of Physicist in Medicine, an incident learning system was specifically established for reporting, investigating, and learning of individual incidents. The incidents that occurred in external beam radiotherapy from February, 2012, to February, 2014, were reported. RESULTS: A total of 28 near misses and 5 incidents were reported. Among them, 5 originated in imaging for planning, 25 in planning, and 1 in plan transfer, commissioning, and delivery, respectively. One near miss/incident was classified as wrong patient, 7 wrong sites, 6 wrong laterality, and 5 wrong dose. Five reported incidents were all classified as grade 1/2 of dosimetric severity, 1 as grade 0, and the other 4 as grade 1 of medical severity. For the causes/contributory factors, negligence, policy not followed, and inadequate training contributed to 19, 15, and 12 near misses/incidents, respectively. The average incident rate per 100 patients treated was 0.4. CONCLUSION: Effective implementation of incident learning can reduce the occurrence of near misses/incidents and enhance the culture of safety. PMID- 25140308 TI - Progress and prospects in human genetic research into age-related hearing impairment. AB - Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i) genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii) candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed. PMID- 25140310 TI - Testing for the endogenous nature between women's empowerment and antenatal health care utilization: evidence from a cross-sectional study in Egypt. AB - Women's relative lack of decision-making power and their unequal access to employment, finances, education, basic health care, and other resources are considered to be the root causes of their ill-health and that of their children. The main purpose of this paper is to examine the interactive relation between women's empowerment and the use of maternal health care. Two model specifications are tested. One assumes no correlation between empowerment and antenatal care while the second specification allows for correlation. Both the univariate and the recursive bivariate probit models are tested. The data used in this study is EDHS 2008. Factor Analysis Technique is also used to construct some of the explanatory variables such as the availability and quality of health services indicators. The findings show that women's empowerment and receiving regular antenatal care are simultaneously determined and the recursive bivariate probit is a better approximation to the relationship between them. Women's empowerment has significant and positive impact on receiving regular antenatal care. The availability and quality of health services do significantly increase the likelihood of receiving regular antenatal care. PMID- 25140311 TI - Treatment of bilateral varicocele and other scrotal comorbidities using a single scrotal access: our experience on 34 patients. AB - INTRODUCTION: Varicocele is the main cause of infertility in male and the most correctable cause of it too. In this study, we present our experience on 34 patients affected by bilateral varicocele and other scrotal comorbidities treated underwent surgery with a scrotal access. MATERIALS AND METHODS: 34 patients were enrolled with clinical palpable and infraclinical (ultrasonic doppler scanning) bilateral varicocele and other comorbidities like right hydrocele, left hydrocele, bilateral hydrocele, and epididymal cyst. They all underwent scrotal bilateral varicocelectomy under local anesthesia. RESULTS AND DISCUSSION: At 6 months, no other complications were reported. No case of testicular atrophy was observed. None had recurrence of varicocele. All scrotal comorbidities were treated as well. CONCLUSION: Scrotal access with local anesthesia is a safe and useful technique to treat patients with bilateral varicocele and other scrotal comorbidities. PMID- 25140312 TI - Effect of prenatal polycyclic aromatic hydrocarbons exposure on birth outcomes: the Polish mother and child cohort study. AB - The aim of this study was to assess the impact of PAH exposure on various anthropometric measures of birth outcomes. The study population consisted of 210 nonsmoking pregnant women. Urine samples collected between 20th and 24th week of pregnancy were used for analysis of the following PAH metabolites: 1-, 2-, 3-, 4 , and 9-hydroxyphenanthrene (1-, 2-, 3-, 4-, and 9-OH-PHE), 1-hydroxypyrene (1-OH PYR), 1,6 + 1,8-dihydroxypyrene (DI-OH-PYR), phenanthrene trans-1,2-dihydrodiol (PHE-1,2-diol), and phenanthrene trans-9,10-dihydrodiol (PHE-9,10-diol) by gas chromatography-mass spectrometry. Environmental tobacco smoke exposure (ETS) was assessed by cotinine level in saliva using a stable isotope dilution LC-ESI-MS/MS method. The mean PAH metabolite concentrations were in the range of 0.15 ug/g creatinine for 9-OH-PHE to 5.9 ug/g creatinine for PHE-9,10-diol. It was shown that none of the individual PAH exposure markers demonstrate a statistically significant influence on birth outcomes. Interestingly a statistically significant association was found between the sum of OH-PHE along with cotinine level and the cephalization index after adjusting for potential confounders (P = 0.04). This study provides evidence that combined exposure of pregnant women to common environmental pollutants such as PAH and ETS might adversely affect fetal development. Thus, reduction of human exposure to these mixtures of hazardous compounds would in particular result in substantial health benefits for newborns. PMID- 25140313 TI - On the coupling of two models of the human immune response to an antigen. AB - The development of mathematical models of the immune response allows a better understanding of the multifaceted mechanisms of the defense system. The main purpose of this work is to present a scheme for coupling distinct models of different scales and aspects of the immune system. As an example, we propose a new model where the local tissue inflammation processes are simulated with partial differential equations (PDEs) whereas a system of ordinary differential equations (ODEs) is used as a model for the systemic response. The simulation of distinct scenarios allows the analysis of the dynamics of various immune cells in the presence of an antigen. Preliminary results of this approach with a sensitivity analysis of the coupled model are shown but further validation is still required. PMID- 25140314 TI - Speech understanding with a new implant technology: a comparative study with a new nonskin penetrating Baha system. AB - OBJECTIVE: To compare hearing and speech understanding between a new, nonskin penetrating Baha system (Baha Attract) to the current Baha system using a skin penetrating abutment. METHODS: Hearing and speech understanding were measured in 16 experienced Baha users. The transmission path via the abutment was compared to a simulated Baha Attract transmission path by attaching the implantable magnet to the abutment and then by adding a sample of artificial skin and the external parts of the Baha Attract system. Four different measurements were performed: bone conduction thresholds directly through the sound processor (BC Direct), aided sound field thresholds, aided speech understanding in quiet, and aided speech understanding in noise. RESULTS: The simulated Baha Attract transmission path introduced an attenuation starting from approximately 5 dB at 1000 Hz, increasing to 20-25 dB above 6000 Hz. However, aided sound field threshold shows smaller differences and aided speech understanding in quiet and in noise does not differ significantly between the two transmission paths. CONCLUSION: The Baha Attract system transmission path introduces predominately high frequency attenuation. This attenuation can be partially compensated by adequate fitting of the speech processor. No significant decrease in speech understanding in either quiet or in noise was found. PMID- 25140316 TI - Intracochlear fluid pressure changes related to the insertional speed of a CI electrode. AB - INTRODUCTION: To preserve residual hearing the atraumaticity of the cochlea electrode insertion has become a focus of cochlear implant research. In addition to other factors, the speed of insertion is thought to be a contributing factor in the concept of atraumatic implantation. The aim of our study was to observe intracochlear fluid pressure changes due to different insertional speeds of an implant electrode in a cochlear model. MATERIALS AND METHODS: The experiments were performed using an artificial cochlear model. A linear actuator was mounted on an Advanced Bionics IJ insertional tool. The intracochlear fluid pressure was recorded through a pressure sensor which was placed in the helicotrema area. Defined insertions were randomly performed with speeds of 0.1 mm/sec, 0.25 mm/sec, 0.5 mm/sec, 1 mm/sec, and 2 mm/sec. RESULTS: A direct correlation between speed and pressure was observed. Mean maximum values of intracochlear fluid pressure varied between 0.41 mm Hg and 1.27 mm Hg. Conclusion. We provide the first results of fluid pressure changes due to insertional speeds of CI electrodes in a cochlear model. A relationship between the insertional speed and intracochlear fluid pressure was observed. Further experiments are needed to apply these results to the in vivo situation. PMID- 25140317 TI - Mesenchymal stem cell-induced doxorubicin resistance in triple negative breast cancer. AB - Triple negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and a worse clinical outcome compared with other breast cancer subtypes. Doxorubicin is considered to be one of the most effective agents in the treatment of TNBC. Unfortunately, resistance to this agent is common. In some drug-resistant cells, drug efflux is mediated by adenosine triphosphate dependent membrane transporter termed adenosine triphosphate-binding cassette (ABC) transporter, which can drive the substrates across membranes against concentration gradient. In the tumor microenvironment, upon interaction with mesenchymal stem cells (MSCs), tumor cells exhibit altered biological functions of certain gene clusters, hence increasing stemness of tumor cells, migration ability, angiogenesis, and drug resistance. In our present study, we investigated the mechanism of TNBC drug resistance induced by adipose-derived MSCs. Upon exposure of TNBC to MSC-secreted conditioned medium (CM), noticeable drug resistance against doxorubicin with markedly increased BCRP protein expression was observed. Intracellular doxorubicin accumulation of TNBC was also decreased by MSC-secreted CM. Furthermore, we found that doxorubicin resistance of TNBC was mediated by IL-8 presented in the MSC-secreted CM. These findings may enrich the list of potential targets for overcoming drug resistance induced by MSCs in TNBC patients. PMID- 25140318 TI - An efficient parallel algorithm for multiple sequence similarities calculation using a low complexity method. AB - With the advance of genomic researches, the number of sequences involved in comparative methods has grown immensely. Among them, there are methods for similarities calculation, which are used by many bioinformatics applications. Due the huge amount of data, the union of low complexity methods with the use of parallel computing is becoming desirable. The k-mers counting is a very efficient method with good biological results. In this work, the development of a parallel algorithm for multiple sequence similarities calculation using the k-mers counting method is proposed. Tests show that the algorithm presents a very good scalability and a nearly linear speedup. For 14 nodes was obtained 12x speedup. This algorithm can be used in the parallelization of some multiple sequence alignment tools, such as MAFFT and MUSCLE. PMID- 25140319 TI - Informative gene selection and direct classification of tumor based on Chi-square test of pairwise gene interactions. AB - In efforts to discover disease mechanisms and improve clinical diagnosis of tumors, it is useful to mine profiles for informative genes with definite biological meanings and to build robust classifiers with high precision. In this study, we developed a new method for tumor-gene selection, the Chi-square test based integrated rank gene and direct classifier (chi(2)-IRG-DC). First, we obtained the weighted integrated rank of gene importance from chi-square tests of single and pairwise gene interactions. Then, we sequentially introduced the ranked genes and removed redundant genes by using leave-one-out cross-validation of the chi-square test-based Direct Classifier (chi(2)-DC) within the training set to obtain informative genes. Finally, we determined the accuracy of independent test data by utilizing the genes obtained above with chi(2)-DC. Furthermore, we analyzed the robustness of chi(2)-IRG-DC by comparing the generalization performance of different models, the efficiency of different feature-selection methods, and the accuracy of different classifiers. An independent test of ten multiclass tumor gene-expression datasets showed that chi(2)-IRG-DC could efficiently control overfitting and had higher generalization performance. The informative genes selected by chi(2)-IRG-DC could dramatically improve the independent test precision of other classifiers; meanwhile, the informative genes selected by other feature selection methods also had good performance in chi(2)-DC. PMID- 25140315 TI - Autophagy in alcohol-induced multiorgan injury: mechanisms and potential therapeutic targets. AB - Autophagy is a genetically programmed, evolutionarily conserved intracellular degradation pathway involved in the trafficking of long-lived proteins and cellular organelles to the lysosome for degradation to maintain cellular homeostasis. Alcohol consumption leads to injury in various tissues and organs including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury in most tissues but could be detrimental in heart and muscle. This review summarizes current knowledge about the role of autophagy in alcohol-induced injury in different tissues/organs and its potential molecular mechanisms as well as possible therapeutic targets based on modulation of autophagy. PMID- 25140320 TI - Ablative therapy for esophageal dysplasia and early malignancy: focus on RFA. AB - Ablative therapies have been utilized with increasing frequency for the treatment of Barrett's esophagus with and without dysplasia. Multiple modalities are available for topical ablation of the esophagus, but radiofrequency ablation (RFA) remains the most commonly used. There have been significant advances in technique since the introduction of RFA. The aim of this paper is to review the indications, techniques, outcomes, and most common complications following esophageal ablation with RFA. PMID- 25140321 TI - Screening of cognitive function and hearing impairment in older adults: a preliminary study. AB - BACKGROUND: Previous research has found that hearing loss is associated with poorer cognitive function. The question is that when a hearing impairment is being compensated for by appropriately fitted monaural hearing aids, special precautions are still needed when screening cognitive function in older adults. OBJECTIVE: This research examined cognitive function in elderly hearing aid users who used monaural hearing aids and whether the presence of a hearing impairment should be accounted for when screening cognitive function in these individuals. METHODS: Auditory thresholds, sentence reception thresholds, and self-reported outcomes with hearing aids were measured in 34 older hearing aid users to ensure hearing aids were appropriately fitted. Mini-Mental State Examination (MMSE) results obtained in these participants were then compared to normative data obtained in a general older population exhibiting similar demographic characteristics. Stepwise multiple regression analyses were used to examine the effects of demographic and auditory variables on MMSE scores. CONCLUSIONS: Results showed that, even with appropriately fitted hearing aids, cognitive decline was significant. Besides the factors commonly measured in the literature, we believed that auditory deprivation was not being fully compensated for by hearing aids. Most importantly, screening of cognitive function should take into account the effects of hearing impairment, even when hearing devices have been appropriately fitted. PMID- 25140323 TI - Cytoskeleton modifications and autophagy induction in TCam-2 seminoma cells exposed to simulated microgravity. AB - The study of how mechanical forces may influence cell behavior via cytoskeleton remodeling is a relevant challenge of nowadays that may allow us to define the relationship between mechanics and biochemistry and to address the larger problem of biological complexity. An increasing amount of literature data reported that microgravity condition alters cell architecture as a consequence of cytoskeleton structure modifications. Herein, we are reporting the morphological, cytoskeletal, and behavioral modifications due to the exposition of a seminoma cell line (TCam-2) to simulated microgravity. Even if no differences in cell proliferation and apoptosis were observed after 24 hours of exposure to simulated microgravity, scanning electron microscopy (SEM) analysis revealed that the change of gravity vector significantly affects TCam-2 cell surface morphological appearance. Consistent with this observation, we found that microtubule orientation is altered by microgravity. Moreover, the confocal analysis of actin microfilaments revealed an increase in the cell width induced by the low gravitational force. Microtubules and microfilaments have been related to autophagy modulation and, interestingly, we found a significant autophagic induction in TCam-2 cells exposed to simulated microgravity. This observation is of relevant interest because it shows, for the first time, TCam-2 cell autophagy as a biological response induced by a mechanical stimulus instead of a biochemical one. PMID- 25140324 TI - Role of CT perfusion in monitoring and prediction of response to therapy of head and neck squamous cell carcinoma. AB - This review aims to summarize the technique and clinical applications of CT perfusion (CTp) of head and neck cancer. The most common pathologic type (90%) of head and neck cancer is squamous cell carcinoma (HNSCC): its diagnostic workup relies on CT and MRI, as they provide an accurate staging for the disease by determining tumour volume, assessing its extension, and detecting of lymph node metastases. Compared with conventional CT and MRI, CTp allows for obtaining measures of tumour vascular physiology and functional behaviour, and it has been demonstrated to be a feasible and useful tool in predicting local outcomes in patients undergoing radiation therapy and chemotherapy and may help monitor both treatments. PMID- 25140322 TI - Alpha-melanocyte stimulating hormone: an emerging anti-inflammatory antimicrobial peptide. AB - The alpha-melanocyte stimulating hormone (alpha-MSH) is a neuropeptide belonging to the melanocortin family. It is well known for its anti-inflammatory and antipyretic effects and shares several characteristics with antimicrobial peptides (AMPs). There have been some recent reports about the direct antimicrobial activity of alpha-MSH against various microbes belonging to both fungal and bacterial pathogens. Similar to alpha-MSH's anti-inflammatory properties, its C-terminal residues also exhibit antimicrobial activity parallel to that of the entire peptide. This review is focused on the current findings regarding the direct antimicrobial potential and immunomodulatory mechanism of alpha-MSH and its C-terminal fragments, with particular emphasis on the prospects of alpha-MSH based peptides as a strong anti-infective agent. PMID- 25140326 TI - Innovations in pancreatic surgery. PMID- 25140325 TI - Prevention and restoration of hearing loss associated with the use of cisplatin. AB - BACKGROUND: Cisplatin is a well known platinum-based chemotherapeutic agent used for the treatment of various malignant tumours. A frequent side effect of cisplatin therapy is ototoxicity. Unfortunately, currently there are no available treatments. MATERIAL AND METHODS: Experimental, clinical studies and reviews published between 2004 and 2014 in the English medical literature concerning ototoxicity were selected using Medline, PubMed, and Google Scholar databases. Inclusion criteria were cisplatin-induced ototoxicity and therapy aimed at preventing or curing this disorder. Molecular mechanisms and clinical, audiological, and histological markers of cisplatin-induced ototoxicity are described. Moreover, experimental and clinical strategies for prevention or treatment of hearing loss were also reviewed. RESULTS AND DISCUSSION: Experimental studies demonstrate a wide range of otoprotective molecules and strategies efficient against cisplatin-induced hearing loss. However, only dexamethasone proved a slight otoprotective effect in a clinical study. CONCLUSION: Further research must be completed to bring future therapeutic options into clinical setting. PMID- 25140328 TI - Modeling and optimization of multiple unmanned aerial vehicles system architecture alternatives. AB - Unmanned aerial vehicle (UAV) systems have already been used in civilian activities, although very limitedly. Confronted different types of tasks, multi UAVs usually need to be coordinated. This can be extracted as a multi UAVs system architecture problem. Based on the general system architecture problem, a specific description of the multi UAVs system architecture problem is presented. Then the corresponding optimization problem and an efficient genetic algorithm with a refined crossover operator (GA-RX) is proposed to accomplish the architecting process iteratively in the rest of this paper. The availability and effectiveness of overall method is validated using 2 simulations based on 2 different scenarios. PMID- 25140327 TI - Airborne biogenic particles in the snow of the cities of the Russian Far East as potential allergic compounds. AB - This paper presents an analysis of airborne biogenic particles (1 mkm-1 mm) found in the snow in several cities of the Russian Far East during 2010-2013. The most common was vegetational terraneous detritus (fragments of tree and grass leaves) followed by animal hair, small insects and their fragments, microorganisms of aeroplankton, and equivocal biological garbage. Specific components were found in samples from locations close to bodies of water such as fragments of algae and mollusc shells and, marine invertebrates (needles of sea urchins and shell debris of arthropods). In most locations across the Far East (Vladivostok, Khabarovsk, Blagoveshchensk, and Ussuriysk), the content of biogenic particles collected in the winter did not exceed 10% of the total particulate matter, with the exception of Birobidzhan and the nature reserve Bastak, where it made up to 20%. Most of all biogenic compounds should be allergic: hair, fragments of tree and grass leaves, insects, and microorganisms. PMID- 25140329 TI - The effects of rape residue mulching on net global warming potential and greenhouse gas intensity from no-tillage paddy fields. AB - A field experiment was conducted to provide a complete greenhouse gas (GHG) accounting for global warming potential (GWP), net GWP, and greenhouse gas intensity (GHGI) from no-tillage (NT) paddy fields with different amounts of oilseed rape residue mulch (0, 3000, 4000, and 6000 kg dry matter (DM) ha(-1)) during a rice-growing season after 3 years of oilseed rape-rice cultivation. Residue mulching treatments showed significantly more organic carbon (C) density for the 0-20 cm soil layer at harvesting than no residue treatment. During a rice growing season, residue mulching treatments sequestered significantly more organic C from 687 kg C ha(-1) season(-1) to 1654 kg C ha(-1) season(-1) than no residue treatment. Residue mulching significantly increased emissions of CO2 and N2O but decreased CH4 emissions. Residue mulching treatments significantly increased GWP by 9-30% but significantly decreased net GWP by 33-71% and GHGI by 35-72% relative to no residue treatment. These results suggest that agricultural economic viability and GHG mitigation can be achieved simultaneously by residue mulching on NT paddy fields in central China. PMID- 25140330 TI - A new graph-based molecular descriptor using the canonical representation of the molecule. AB - Molecular similarity is a pervasive concept in drug design. The basic idea underlying molecular similarity is the similar property principle, which states that structurally similar molecules will exhibit similar physicochemical and biological properties. In this paper, a new graph-based molecular descriptor (GBMD) is introduced. The GBMD is a new method of obtaining a rough description of 2D molecular structure in textual form based on the canonical representations of the molecule outline shape and it allows rigorous structure specification using small and natural grammars. Simulated virtual screening experiments with the MDDR database show clearly the superiority of the graph-based descriptor compared to many standard descriptors (ALOGP, MACCS, EPFP4, CDKFP, PCFP, and SMILE) using the Tanimoto coefficient (TAN) and the basic local alignment search tool (BLAST) when searches were carried. PMID- 25140331 TI - A novel deployment method for communication-intensive applications in service clouds. AB - The service platforms are migrating to clouds for reasonably solving long construction periods, low resource utilizations, and isolated constructions of service platforms. However, when the migration is conducted in service clouds, there is a little focus of deploying communication-intensive applications in previous deployment methods. To address this problem, this paper proposed the combination of the online deployment and the offline deployment for deploying communication-intensive applications in service clouds. Firstly, the system architecture was designed for implementing the communication-aware deployment method for communication-intensive applications in service clouds. Secondly, in the online-deployment algorithm and the offline-deployment algorithm, service instances were deployed in an optimal cloud node based on the communication overhead which is determined by the communication traffic between services, as well as the communication performance between cloud nodes. Finally, the experimental results demonstrated that the proposed methods deployed communication-intensive applications effectively with lower latency and lower load compared with existing algorithms. PMID- 25140332 TI - A review of subsequence time series clustering. AB - Clustering of subsequence time series remains an open issue in time series clustering. Subsequence time series clustering is used in different fields, such as e-commerce, outlier detection, speech recognition, biological systems, DNA recognition, and text mining. One of the useful fields in the domain of subsequence time series clustering is pattern recognition. To improve this field, a sequence of time series data is used. This paper reviews some definitions and backgrounds related to subsequence time series clustering. The categorization of the literature reviews is divided into three groups: preproof, interproof, and postproof period. Moreover, various state-of-the-art approaches in performing subsequence time series clustering are discussed under each of the following categories. The strengths and weaknesses of the employed methods are evaluated as potential issues for future studies. PMID- 25140333 TI - An improved multidimensional MPA procedure for bidirectional earthquake excitations. AB - Presently, the modal pushover analysis procedure is extended to multidimensional analysis of structures subjected to multidimensional earthquake excitations. an improved multidimensional modal pushover analysis (IMMPA) method is presented in the paper in order to estimate the response demands of structures subjected to bidirectional earthquake excitations, in which the unidirectional earthquake excitation applied on equivalent SDOF system is replaced by the direct superposition of two components earthquake excitations, and independent analysis in each direction is not required and the application of simplified superposition formulas is avoided. The strength reduction factor spectra based on superposition of earthquake excitations are discussed and compared with the traditional strength reduction factor spectra. The step-by-step procedure is proposed to estimate seismic demands of structures. Two examples are implemented to verify the accuracy of the method, and the results of the examples show that (1) the IMMPA method can be used to estimate the responses of structure subjected to bidirectional earthquake excitations. (2) Along with increase of peak of earthquake acceleration, structural response deviation estimated with the IMMPA method may also increase. (3) Along with increase of the number of total floors of structures, structural response deviation estimated with the IMMPA method may also increase. PMID- 25140334 TI - Nonlinear secret image sharing scheme. AB - Over the past decade, most of secret image sharing schemes have been proposed by using Shamir's technique. It is based on a linear combination polynomial arithmetic. Although Shamir's technique based secret image sharing schemes are efficient and scalable for various environments, there exists a security threat such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing technique based on nonlinear combination polynomial arithmetic in order to solve this threat. It is hard to apply to the secret image sharing. In this paper, we propose a (t, n)-threshold nonlinear secret image sharing scheme with steganography concept. In order to achieve a suitable and secure secret image sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean algebra operation, define a new variable m, and change a range of prime p in sharing procedure. In order to evaluate efficiency and security of proposed scheme, we use the embedding capacity and PSNR. As a result of it, average value of PSNR and embedding capacity are 44.78 (dB) and 1.74t?log2 m? bit-per-pixel (bpp), respectively. PMID- 25140336 TI - Compressive strength, chloride permeability, and freeze-thaw resistance of MWNT concretes under different chemical treatments. AB - This study investigated compressive strength, chloride penetration, and freeze thaw resistance of multiwalled carbon nanotube (MWNT) concrete. More than 100 cylindrical specimens were used to assess test variables during sensitivity observations, including water-cement ratios (0.75, 0.5, and 0.4) and exposure to chemical agents (including gum arabic, propanol, ethanol, sodium polyacrylate, methylcellulose, sodium dodecyl sulfate, and silane). To determine the adequate sonication time for MWNT dispersal in water, the compressive strengths of MWNT concrete cylinders were measured after sonication times ranging from 2 to 24 minutes. The results demonstrated that the addition of MWNT can increase the compressive strength of concrete by up to 108%. However, without chemical treatment, MWNT concretes tend to have poor freeze-thaw resistance. Among the different chemical treatments, MWNT concrete treated with sodium polyacrylate has the best compressive strength, chloride resistance, and freeze-thaw durability. PMID- 25140335 TI - HPLC-fingerprints and antioxidant constituents of Phyla nodiflora. AB - Phyla nodiflora is a creeping perennial herb, widely distributed in the most tropical and subtropical regions. It has been used as a folk medicine, herbal beverage, or folk cosmetic. For these usages, the development of a chemical quality control method of this plant is necessary. In the present study, ten compounds, namely, 3,7,4',5'-tetrahydroxy-3'-methoxyflavone (1), nodifloretin (2), 4'-hydroxywogonin (3), onopordin (4), cirsiliol (5), 5,7,8,4'-tetrahydroxy 3'-methoxyflavone (6), eupafolin (7), hispidulin (8), larycitrin (9), and beta sitosterol were isolated from the methanolic extract of the aerial part of P. nodiflora (PNM) and their structures were identified by 1D-NMR comparing their spectra with the literature. The antioxidant activities of these compounds were evaluated by free radical scavenging activity and tyrosinase inhibitory effect in cell-free systems. Compounds 4, 5, and 7 showed strong antioxidant activity. To control the quality of P. nodiflora, a simple and reliable method of high performance liquid chromatography combined with ultraviolet detector (HPLC-UV) was established for both the fingerprint analysis and the quantitative determination of two selected active compounds, onopordin (4) and eupafolin (7). Statistical analysis of the obtained data demonstrated that our method achieved the desired linearity, precision, and accuracy. The results indicated that the developed method can be used as a quality evaluation method for PNM. PMID- 25140338 TI - Hesitant triangular fuzzy information aggregation operators based on Bonferroni means and their application to multiple attribute decision making. AB - We investigate the multiple attribute decision-making (MADM) problems with hesitant triangular fuzzy information. Firstly, definition and some operational laws of hesitant triangular fuzzy elements are introduced. Then, we develop some hesitant triangular fuzzy aggregation operators based on Bonferroni means and discuss their basic properties. Some existing operators can be viewed as their special cases. Next, we apply the proposed operators to deal with multiple attribute decision-making problems under hesitant triangular fuzzy environment. Finally, an illustrative example is given to show the developed method and demonstrate its practicality and effectiveness. PMID- 25140337 TI - Tunneling and suture of thoracic epidural catheters decrease the incidence of catheter dislodgement. AB - BACKGROUND: Dislocation of epidural catheters (EC) is associated with early termination of regional analgesia and rare complications like epidural bleeding. We tested the hypothesis that maximum effort in fixation by tunneling and suture decreases the incidence of catheter dislocation. METHODS: Patients scheduled for major surgery (n = 121) were prospectively randomized in 2 groups. Thoracic EC were subcutaneously tunneled and sutured (tunneled) or fixed with adhesive tape (taped). The difference of EC length at skin surface level immediately after insertion and before removal was determined and the absolute values were averaged. Postoperative pain was evaluated by numeric rating scale twice daily and EC tips were screened microbiologically after removal. RESULTS: Both groups did not differ with respect to treatment duration (tunneled: 109 hours +/- 46, taped: 97 +/- 37) and postoperative pain scores. Tunneling significantly reduced average extent (tunneled: 3 mm +/- 7, taped: 10 +/- 18) and incidence of clinically relevant EC dislocation (>20 mm, tunneled: 1/60, taped: 9/61). Bacterial contamination showed a tendency to be lower in patients with tunneled catheters (8/59, taped: 14/54, P = 0.08). CONCLUSION: Thorough fixation of EC by tunneling and suturing decreases the incidence and extent of dislocation and potentially even that of bacterial contamination. PMID- 25140339 TI - MAC protocol for ad hoc networks using a genetic algorithm. AB - The problem of obtaining the transmission rate in an ad hoc network consists in adjusting the power of each node to ensure the signal to interference ratio (SIR) and the energy required to transmit from one node to another is obtained at the same time. Therefore, an optimal transmission rate for each node in a medium access control (MAC) protocol based on CSMA-CDMA (carrier sense multiple access code division multiple access) for ad hoc networks can be obtained using evolutionary optimization. This work proposes a genetic algorithm for the transmission rate election considering a perfect power control, and our proposition achieves improvement of 10% compared with the scheme that handles the handshaking phase to adjust the transmission rate. Furthermore, this paper proposes a genetic algorithm that solves the problem of power combining, interference, data rate, and energy ensuring the signal to interference ratio in an ad hoc network. The result of the proposed genetic algorithm has a better performance (15%) compared to the CSMA-CDMA protocol without optimizing. Therefore, we show by simulation the effectiveness of the proposed protocol in terms of the throughput. PMID- 25140340 TI - Performance analysis of single-frequency MPPSK integrated system for ranging applications. AB - The dual-frequency MPPSK-MODEM is a flexible platform. When ranging accuracy request is low or platform is particularly limited by power, the platform would perform both data transmission and range measurement with single-frequency modes. In this paper, the ranging resolution of MPPSK pulse waveforms with the match filter and impacting filter processing are discussed, respectively. Also, the parameter selection of MPPSK modulator for ranging is considered. In particular, requirements that allow for employing such special parameter values for range measurements with high accuracy and high range are investigated. Moreover, high repetition frequency (HRF) biphase code MPPSK pulse train base on m sequence is presented, and the ranging accuracy of the proposed signal with the match filter processing is deduced. In addition to theoretical considerations, the paper presents system simulations and measurement results of single-frequency MPPSK integrated systems, demonstrating the high-performance of ranging applications. PMID- 25140342 TI - Integrated system of structural health monitoring and intelligent management for a cable-stayed bridge. AB - It is essential to construct structural health monitoring systems for large important bridges. Zhijiang Bridge is a cable-stayed bridge that was built recently over the Hangzhou Qiantang River (the largest river in Zhejiang Province). The length of Zhijiang Bridge is 478 m, which comprises an arched twin tower space and a twin-cable plane structure. As an example, the present study describes the integrated system of structural health monitoring and intelligent management for Zhijiang Bridge, which comprises an information acquisition system, data management system, evaluation and decision-making system, and application service system. The monitoring components include the working environment of the bridge and various factors that affect bridge safety, such as the stress and strain of the main bridge structure, vibration, cable force, temperature, and wind speed. In addition, the integrated system includes a forecasting and decision-making module for real-time online evaluation, which provides warnings and makes decisions based on the monitoring information. From this, the monitoring information, evaluation results, maintenance decisions, and warning information can be input simultaneously into the bridge monitoring center and traffic emergency center to share the monitoring data, thereby facilitating evaluations and decision making using the system. PMID- 25140341 TI - Extract of Antrodia camphorata exerts neuroprotection against embolic stroke in rats without causing the risk of hemorrhagic incidence. AB - In this study, the neuroprotective effect of an extract of Antrodia camphorata (A. camphorata), a fungus commonly used in Chinese folk medicine for treatment of viral hepatitis and cancer, alone or in combination with aspirin was investigated in a rat embolic stroke model. An ischemic stroke was induced in rats by a selective occlusion of the middle cerebral artery (MCA) with whole blood clots and then orally treated with A. camphorata (0.25 and 0.75 g/kg/day) alone and combined with aspirin (5 mg/kg/day). Sixty days later, the brains were removed, sectioned, and stained with triphenyltetrazolium chloride and analysed by a commercial image processing software program. Brain infarct volume, neurobehavioral score, cerebral blood perfusion, and subarachnoid and intracerebral hemorrhage incidence were perceived. In addition, potential bleeding side effect of the combinative therapy was assessed by measuring hemoglobin (Hb) content during intracerebral hemorrhage and gastric bleeding, prothrombin time (PT), and occlusion time (OT) after oral administration. Posttreatment with high dose A. camphorata significantly reduced infarct volume and improved neurobehavioral score (P < 0.05). Since A. camphorata alone or with aspirin did not alter the Hb level, this treatment is safe and does not cause hemorrhagic incident. Remarkably, the combination of A. camphorata and aspirin did not show a significant effect on the bleeding time, PT and OT increase suggesting that A. camphorata may have the neuroprotective effect without the prolongation of bleeding time or coagulation time. From these observations, we suggest that combinative therapy of A. camphorata and aspirin might offer enhanced neuroprotective efficacies without increasing side effects. PMID- 25140343 TI - Application of empirical mode decomposition with local linear quantile regression in financial time series forecasting. AB - This paper mainly forecasts the daily closing price of stock markets. We propose a two-stage technique that combines the empirical mode decomposition (EMD) with nonparametric methods of local linear quantile (LLQ). We use the proposed technique, EMD-LLQ, to forecast two stock index time series. Detailed experiments are implemented for the proposed method, in which EMD-LPQ, EMD, and Holt-Winter methods are compared. The proposed EMD-LPQ model is determined to be superior to the EMD and Holt-Winter methods in predicting the stock closing prices. PMID- 25140345 TI - Displacement back analysis for a high slope of the Dagangshan Hydroelectric Power Station based on BP neural network and particle swarm optimization. AB - The right bank high slope of the Dagangshan Hydroelectric Power Station is located in complicated geological conditions with deep fractures and unloading cracks. How to obtain the mechanical parameters and then evaluate the safety of the slope are the key problems. This paper presented a displacement back analysis for the slope using an artificial neural network model (ANN) and particle swarm optimization model (PSO). A numerical model was established to simulate the displacement increment results, acquiring training data for the artificial neural network model. The backpropagation ANN model was used to establish a mapping function between the mechanical parameters and the monitoring displacements. The PSO model was applied to initialize the weights and thresholds of the backpropagation (BP) network model and determine suitable values of the mechanical parameters. Then the elastic moduli of the rock masses were obtained according to the monitoring displacement data at different excavation stages, and the BP neural network model was proved to be valid by comparing the measured displacements, the displacements predicted by the BP neural network model, and the numerical simulation using the back-analyzed parameters. The proposed model is useful for rock mechanical parameters determination and instability investigation of rock slopes. PMID- 25140344 TI - Management of mango hopper, Idioscopus clypealis, using chemical insecticides and Neem oil. AB - An experiment was conducted in Field Laboratory, Department of Entomology at Bangladesh Agricultural University, Mymensingh, during 2013 to manage the mango hopper, Idioscopus clypealis L, using three chemical insecticides, Imidacloprid (0.3%), Endosulfan (0.5%), and Cypermethrin (0.4%), and natural Neem oil (3%) with three replications of each. All the treatments were significantly effective in managing mango hopper in comparison to the control. Imidacloprid showed the highest efficacy in percentage of reduction of hopper population (92.50 +/- 9.02) at 72 hours after treatment in case of 2nd spray. It also showed the highest overall percentage of reduction (88.59 +/- 8.64) of hopper population and less toxicity to natural enemies including green ant, spider, and lacewing of mango hopper. In case of biopesticide, azadirachtin based Neem oil was found effective against mango hopper as 48.35, 60.15, and 56.54% reduction after 24, 72, and 168 hours of spraying, respectively, which was comparable with Cypermethrin as there was no statistically significant difference after 168 hours of spray. Natural enemies were also higher after 1st and 2nd spray in case of Neem oil. PMID- 25140346 TI - CUDT: a CUDA based decision tree algorithm. AB - Decision tree is one of the famous classification methods in data mining. Many researches have been proposed, which were focusing on improving the performance of decision tree. However, those algorithms are developed and run on traditional distributed systems. Obviously the latency could not be improved while processing huge data generated by ubiquitous sensing node in the era without new technology help. In order to improve data processing latency in huge data mining, in this paper, we design and implement a new parallelized decision tree algorithm on a CUDA (compute unified device architecture), which is a GPGPU solution provided by NVIDIA. In the proposed system, CPU is responsible for flow control while the GPU is responsible for computation. We have conducted many experiments to evaluate system performance of CUDT and made a comparison with traditional CPU version. The results show that CUDT is 5 ~ 55 times faster than Weka-j48 and is 18 times speedup than SPRINT for large data set. PMID- 25140347 TI - Characterization of the complete nuclear ribosomal DNA sequences of Paramphistomum cervi. AB - Sequences of the complete nuclear ribosomal DNA (rDNA) gene from five individual Paramphistomum cervi were determined for the first time. The five complete rDNA sequences, which included the 18S rDNA, the internal transcribed spacer 1 (ITS1), the 5.8S rDNA, the internal transcribed spacer 2 (ITS2), the 28S rDNA, and the intergenic spacer (IGS) regions, had a length range of 8,493-10,221 bp. The lengths of the investigated 18S, ITS1, 5.8S, ITS2, and 28S rDNA sequences, which were 1,994 bp, 1,293 bp, 157 bp, 286 bp, and 4,186 bp, respectively, did not vary. However, the IGS rDNA sequences had a length range of 577-2,305 bp. The 5.8S and ITS-2 rDNA sequences had 100% identity among the five investigated samples, while the identities among the IGS had a range of 53.7-99.8%. A comparative analysis revealed that different types and numbers of repeats were found within each ITS1 and IGS region, which may be related to the length polymorphism of IGS. The phylogenetic position of P. cervi in Paramphistomatidae was analyzed based on the 18S rDNA sequences. These results will aid in studying the intra- and interspecific variation of the Paramphistomatidae and the systematics and phylogenetics of Digenea. PMID- 25140348 TI - Effects of salt-drought stress on growth and physiobiochemical characteristics of Tamarix chinensis seedlings. AB - The present study was designed to clarify the effects of salinity and water intercross stresses on the growth and physiobiochemical characteristics of Tamarix chinensis seedlings by pots culture under the artificial simulated conditions. The growth, activities of SOD, POD, and contents of MDA and osmotic adjusting substances of three years old seedlings of T. chinensis were studied under different salt-drought intercross stress. Results showed that the influence of salt stress on growth was greater than drought stress, the oxidation resistance of SOD and POD weakened gradually with salt and drought stresses intensified, and the content of MDA was higher under severe drought and mild and moderate salt stresses. The proline contents increased with the stress intensified but only significantly higher than control under the intercross stresses of severe salt-severe drought. It implied that T. chinensis could improve its stress resistance by adjusted self-growth and physiobiochemical characteristics, and the intercross compatibility of T. chinensis to salt and drought stresses can enhance the salt resistance under appropriate drought stress, but the dominant factors influencing the physiological biochemical characteristics of T. chinensis were various with the changing of salt-drought intercross stresses gradients. PMID- 25140349 TI - Distribution, microfabric, and geochemical characteristics of siliceous rocks in central orogenic belt, China: implications for a hydrothermal sedimentation model. AB - Marine siliceous rocks are widely distributed in the central orogenic belt (COB) of China and have a close connection to the geological evolution and metallogenesis. They display periodic distributions from Mesoproterozoic to Jurassic with positive peaks in the Mesoproterozoic, Cambrian--Ordovician, and Carboniferous--Permian and their deposition is enhanced by the tensional geological settings. The compressional regimes during the Jinning, Caledonian, Hercynian, Indosinian, and Yanshanian orogenies resulted in sudden descent in their distribution. The siliceous rocks of the Bafangshan-Erlihe ore deposit include authigenic quartz, syn-depositional metal sulphides, and scattered carbonate minerals. Their SiO2 content (71.08-95.30%), Ba (42.45-503.0 ppm), and SigmaREE (3.28-19.75 ppm) suggest a hydrothermal sedimentation origin. As evidenced by the Al/(Al + Fe + Mn), Sc/Th, (La/Yb) N, and (La/Ce) N ratios and deltaCe values, the studied siliceous rocks were deposited in a marginal sea basin of a limited ocean. We suggest that the Bafangshan-Erlihe area experienced high- and low-temperature stages of hydrothermal activities. The hydrothermal sediments of the former stage include metal sulphides and silica, while the latter was mainly composed of silica. Despite the hydrothermal sedimentation of the siliceous rocks, minor terrigenous input, magmatism, and biological activity partly contributed to geochemical features deviating from the typical hydrothermal characteristics. PMID- 25140350 TI - Reinforcement learning for routing in cognitive radio ad hoc networks. AB - Cognitive radio (CR) enables unlicensed users (or secondary users, SUs) to sense for and exploit underutilized licensed spectrum owned by the licensed users (or primary users, PUs). Reinforcement learning (RL) is an artificial intelligence approach that enables a node to observe, learn, and make appropriate decisions on action selection in order to maximize network performance. Routing enables a source node to search for a least-cost route to its destination node. While there have been increasing efforts to enhance the traditional RL approach for routing in wireless networks, this research area remains largely unexplored in the domain of routing in CR networks. This paper applies RL in routing and investigates the effects of various features of RL (i.e., reward function, exploitation, and exploration, as well as learning rate) through simulation. New approaches and recommendations are proposed to enhance the features in order to improve the network performance brought about by RL to routing. Simulation results show that the RL parameters of the reward function, exploitation, and exploration, as well as learning rate, must be well regulated, and the new approaches proposed in this paper improves SUs' network performance without significantly jeopardizing PUs' network performance, specifically SUs' interference to PUs. PMID- 25140351 TI - Counteracting the inhibitory effect of proteins towards lung surfactant substitutes: a fluorocarbon gas helps displace albumin at the air/water interface. AB - Perfluorohexane gas lowers the kinetic barrier that opposes the displacement of albumin by dipalmitoylphosphatidylcholine at the air/water interface submitted to sinusoidal oscillations at frequencies in the range of those encountered in respiration. PMID- 25140352 TI - Colorimetric and fluorescent determination of sulfide and sulfite with kinetic discrimination. AB - Two fluorescent probes, m-PSP and p-PSP , for sulfite and/or sulfide were constructed by connecting a pyridinium ion to a coumarin fluorophore through an alpha,beta-unsaturated ketone. The presence of the pyridinium salt promoted the nucleophilic addition of sulfite and sulfide to the alpha,beta-unsaturated ketone, which could be visualized by dramatic changes in the solution's color and fluorescence intensity. Both probes exhibit good selectivity (the selectivity coefficients toward major interferences are less than 0.07) and high sensitivity for sulfite and sulfide over biothiols and other potential analytes. The detection limits of m-PSP for the analysis of sulfite and sulfide are calculated to 8.5 * 10(-7) M and 2.7 * 10(-7) M, respectively. Living cell imaging results indicate that both probes can be applied in biological systems. PMID- 25140353 TI - High-yield photolytic generation of brominated single-walled carbon nanotubes and their application for gas sensing. AB - We present a facile and efficient photobromination technique for the covalent sidewall functionalization of SWNT using N-bromosuccinamide as the bromine source. The modified bromine functionalized SWNTs are used as active agents in a resistance measuring electrode system for sensing and discrimination of analyte vapors. PMID- 25140354 TI - GdF3 as a promising phosphopeptide affinity probe and dephospho-labelling medium: experiments and theoretical explanation. AB - Bone-like GdF3 was synthesized and applied for phosphopeptide enrichment for the first time. As a new kind of efficient phosphopeptide affinity probe, GdF3 exhibits high efficiency in the mediation of the dephosphorylation reaction. In addition, DFT calculations were introduced to theoretically explain the unique property of GdF3 compared to GdPO4, which is promising and can be potentially significant in protein phosphorylation research. PMID- 25140355 TI - Lanthanoid beta-triketonates: a new class of highly efficient NIR emitters for bright NIR-OLEDs. AB - The reaction of hydrated YbCl3 with potassium tribenzoylmethanide yields a new bimetallic tetranuclear Yb(3+)/K(+) assembly. This species not only possesses the longest excited state lifetime and quantum yield reported for the Yb(3+) diketonate family but is also suitable to be incorporated in NIR-OLEDs, whose performance outclasses any other reported lanthanoid-based device with NIR emission. PMID- 25140356 TI - Reformation of organic dicarboxylate electrode materials for rechargeable batteries by molecular self-assembly. AB - We have found that the specific capacity of a Li-intercalated metal-organic framework (iMOF) electrode material, 2,6-naphthalene dicarboxylate dilithium, can be increased by narrowing the distance between naphthalene layers via ordering. The increase in specific capacity can be attributed to formation of more efficient electron and ion pathways in the framework. PMID- 25140357 TI - Morphological effect of gold nanoparticles on the adsorption of bovine serum albumin. AB - Various properties of gold nanoparticles (GNPs) are found to play crucial roles in their biological activity. Among them, the morphology and surface chemistry are extremely important. This is because of differences in surface energies of various crystal facets arising from a large fraction of edges, corners and vertices. In the present work, we provide a comparative study on the adsorption and binding affinities of bovine serum albumin (BSA) onto triangular gold nanoplates (TGNP) and gold nanorods (GNR). The results were compared with similar size of both CTAB and citrate stabilized spherical GNPs. Our data suggested stronger binding of BSA on citrate stabilized spherical GNPs whereas TGNP shows the weakest binding among all the GNPs. A blue shift of approximately 20 nm in tryptophan fluorescence was observed for all CTAB stabilized GNPs, indicating the local dielectric changes surrounding the tryptophan residue. Loss of the secondary structure was also observed for all CTAB stabilized GNPs. No spectral shift was observed for citrate stabilized spherical GNPs though maximum quenching of fluorescence and minimum structural loss was observed. With the help of molecular simulation recently developed by our group, a binding model is proposed to explain all the above experimental results. PMID- 25140358 TI - Anomalous high adsorption energy of H2O on fluorinated graphenes: a first principles study. AB - Polytetrafluoroethylene (PTFE) has been well-known for the surface superhydrophobicity, while its two-dimensional stable analogues, CF and C4F, possess distinct surface wettability. The CF inherits the hydrophobicity from PTFE since the van der Waals interaction is mitigated by the high electronegativity of fluorine. Surprisingly, a high adsorption energy (~550 meV per molecule) of water has been unveiled on C4F via density functional theory studies, implying anomalous superhydrophilicity of C4F. The abrupt transition from hydrophobicity of CF to superhydrophilicity of C4F can be reconciled with the difference in their molecular orbitals. The high adsorption energy of C4F is mainly attributed to the Coulomb attraction among the non-bonding interactions, as proposed by our theoretical model. Since the surface chemical inertness of CF inhibits it from being widely adopted in device fabrication, the present finding suggests that C4F can be a promising candidate in graphene-based electronic devices. PMID- 25140359 TI - Tip-enhanced Raman spectroscopic measurement of stress change in the local domain of epitaxial graphene on the carbon face of 4H-SiC(000-1). AB - We develop a bulk silver tip for tip-enhanced Raman scattering (TERS) and obtain TERS spectra of epitaxial graphene on the carbon face of 4H-SiC(000-1) with a high signal-to-noise ratio. Thanks to the high quality of TERS spectra we firstly find that the G band in the TERS spectra exhibits position-by-position variations in both lower wavenumber shifts and spectral broadening. The analysis of the variations reveals that the shifts and broadenings have a linear correlation between each other, indicating that the variations are induced by the position dependent local stress on graphene based on a uniaxial strain model. PMID- 25140360 TI - Electronic stability and electron transport properties of atomic wires anchored on the MoS2 monolayer. AB - The stability, electronic structure, and electron transport properties of metallic monoatomic wires anchored on the MoS2 monolayer are investigated within the density functional theory. The anchoring of the atomic wires on the semiconducting monolayer significantly modifies its electronic properties; the metallic characteristics of the assembled monolayers appear in the density of states and band structure of the system. We find that Cu, Ag and Au wires induce the so-called n-type doping effect, whereas Pt wires induce a p-type doping effect in the monolayer. The distinctly different behavior of Pt-MoS2 compared to the rest of the metallic wires is reflected in the calculated current-voltage characteristics of the assembled monolayers with a highly asymmetric behavior of the out-of-the-plane tunneling current with respect to the polarity of the external bias. The results of the present study are likely to extend the functionality of the MoS2 monolayer as a candidate material for the novel applications in the areas of catalysis and optoelectronic devices. PMID- 25140361 TI - Agarose gel investigation of quantum dots conjugated with short ssDNA. AB - Herein, we investigate the migration distance of quantum-dot-functionalized complexes in electrophoresis. The quantitative study of these moving particles in an electrophoretic environment is modeled using an extended Smoluchowski equation. An extended Smoluchowski equation is proposed to addressed the D(m) to Ln(N) plot slope variation issue present in previous work and agreement between experiment and theory is found. The procedures underlying this work then discusses the potential of using agarose electrophoresis as a mean of monitoring the composition of nano-complexes consisting of quantum dots functionalized with differing numbers of DNA molecules. PMID- 25140362 TI - Cluster algebras. PMID- 25140363 TI - Reducing complications from obstructive sleep apnoea. PMID- 25140366 TI - Japan: in the wake of the 2011 tsunami. PMID- 25140365 TI - Third-generation EGFR-TKIs-a new hope for NSCLC. PMID- 25140364 TI - 2014 American Thoracic Society International Conference. PMID- 25140367 TI - AstraZeneca Pharmaceuticals launches in Zambia. PMID- 25140369 TI - Sports cardiology: preventing sudden cardiac death. PMID- 25140370 TI - Visual working memory. Models of response times. PMID- 25140371 TI - Spatiotemporal context. How past perception influences current perception. PMID- 25140372 TI - Attention and reward. The power of reward to rewire attention. PMID- 25140373 TI - Color vision. The "geopolitics" of basic color terms. PMID- 25140374 TI - Timing. Autocracy versus democracy in a string quartet. PMID- 25140375 TI - Artistic skill and object perception. Drawing skill: neither the eye nor the hand, but something in between. PMID- 25140376 TI - Authors' reply. PMID- 25140377 TI - Reply to the 'Comment on comparison of powder dustiness methods' by Douglas Evans, Leonid Turkevich, Cynthia Roettgers, and Gregory Deye (Ann. Occup. Hyg., 2014, Vol. 58, No. 4, 524-8). PMID- 25140378 TI - Reply to the letters to the editor submitted by T. L. Ogden and K.T. Du Clos, and by R. Foster regarding the paper 'SWeRF-a method for estimating the relevant fine particle fraction in bulk materials for classification and labelling purposes'. AB - The authors respond to the points raised in the Letters to the Editor raised by Ogden and Du Clos and by Foster. Ad 1: The debate of the classification of respirable cyrstalline silica is outside the scope of the technical paper. Ad 2: A standard for the determination of SWeRF is under development, in which indeed the provision is made that for a correct determination all quartz within the fine fraction needs to be liberated. Ad 3: Dustiness tests provide useful information for occupational hygienists, but are not suitable for fulfilling classification and labelling requirements. Ad 4: Pipette effects are not discussed in the paper because the difference between calculating the SWeRF from the particle size distribution and the SWeRF from sedimentation is very small. PMID- 25140380 TI - Supermarket smarts. Diner-style breakfast foods. PMID- 25140379 TI - Aging and DNA damage in humans: a meta-analysis study. AB - Age-related DNA damage is regarded as one of the possible explanations of aging. Although a generalized idea about the accumulation of DNA damage with age exists, results found in the literature are inconsistent. To better understand the question of age-related DNA damage in humans and to identify possible moderator variables, a metaanalysis was conducted. Electronic databases and bibliographies for studies published since 2004 were searched. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for age-related DNA damage were calculated in a random effects model. A total of 76 correlations from 36 studies with 4676 participants were included. Based on our analysis, a correlation between age and DNA damage was found (r=0.230, p=0.000; 95% confidence interval=0.111-0.342). The test for heterogeneity of variance indicates that the study's results are significantly high (Q (75)=1754.831, p=0.000). Moderator variables such as smoking habits, technique used, and the tissue/sample analyzed, are shown to influence age related DNA damage (p=0.026; p=0.000; p=0.000, respectively). Nevertheless, sex did not show any influence on this relation (p=0.114). In conclusion, this meta analysis showed an association between age and DNA damage in humans. It was also found that smoking habits, the technique used, and tissue/sample analyzed, are important moderator variables in age-related DNA damage. PMID- 25140381 TI - Most profitable U.S. health insurance companies. Ranked by 2013 profit margin. PMID- 25140382 TI - Largest not-for-profit hospital systems. Ranked by total revenue for 2013. PMID- 25140383 TI - Conductance control in VO2 nanowires by surface doping with gold nanoparticles. AB - The material properties of semiconductor nanowires are greatly affected by electrical, optical, and chemical processes occurring at their surfaces because of the very large surface-to-volume ratio. Precise control over doping as well as the surface charge properties has been demonstrated in thin films and nanowires for fundamental physics and application-oriented research. However, surface doping behavior is expected to differ markedly from bulk doping in conventional semiconductor materials. Here, we show that placing gold nanoparticles, in controlled manner, on the surface of an insulating vanadium dioxide nanowire introduces local charge carriers in the nanowire, and one could, in principle, completely and continuously alter the material properties of the nanowire and obtain any intermediate level of conductivity. The current in the nanowire increased by nearly 3 times when gold nanoparticles of 10(11) cm(-2) order of density were controllably placed on the nanowire surface. A strong quadratic space-charge limited (SCL) transport behavior was also observed from the conductance curve suggesting the formation of two-dimensional (2D) electron-gas like confined layer in the nanowire with adsorbed Au NPs. In addition to stimulating scientific interest, such unusual surface doping phenomena may lead to new applications of vanadium dioxide-based electronic, optical, and chemical sensing nanodevices. PMID- 25140384 TI - Weakly anti-inflammatory limonoids from the seeds of Xylocarpus rumphii. AB - Seven new limonoids, namely, xylorumphiins E-J (1-2 and 4-7) and 2 hydroxyxylorumphiin F (3), along with three known derivatives (8-10), were isolated from the seeds of Xylocarpus rumphii. 2-Hydroxyxylorumphiin F (3) and xylorumphiin I (6) displayed moderate inhibitory activity against nitric oxide production from lipopolysaccharide-activated macrophages with IC50 values of 24.5 and 31.3 MUM, respectively. PMID- 25140385 TI - 13C NMR metabolomics: applications at natural abundance. AB - (13)C NMR has many advantages for a metabolomics study, including a large spectral dispersion, narrow singlets at natural abundance, and a direct measure of the backbone structures of metabolites. However, it has not had widespread use because of its relatively low sensitivity compounded by low natural abundance. Here we demonstrate the utility of high-quality (13)C NMR spectra obtained using a custom (13)C-optimized probe on metabolomic mixtures. A workflow was developed to use statistical correlations between replicate 1D (13)C and (1)H spectra, leading to composite spin systems that can be used to search publicly available databases for compound identification. This was developed using synthetic mixtures and then applied to two biological samples, Drosophila melanogaster extracts and mouse serum. Using the synthetic mixtures we were able to obtain useful (13)C-(13)C statistical correlations from metabolites with as little as 60 nmol of material. The lower limit of (13)C NMR detection under our experimental conditions is approximately 40 nmol, slightly lower than the requirement for statistical analysis. The (13)C and (1)H data together led to 15 matches in the database compared to just 7 using (1)H alone, and the (13)C correlated peak lists had far fewer false positives than the (1)H generated lists. In addition, the (13)C 1D data provided improved metabolite identification and separation of biologically distinct groups using multivariate statistical analysis in the D. melanogaster extracts and mouse serum. PMID- 25140387 TI - Mixtures as a fungicide resistance management tactic. AB - We have reviewed the experimental and modeling evidence on the use of mixtures of fungicides of differing modes of action as a resistance management tactic. The evidence supports the following conclusions. 1. Adding a mixing partner to a fungicide that is at-risk of resistance (without lowering the dose of the at-risk fungicide) reduces the rate of selection for fungicide resistance. This holds for the use of mixing partner fungicides that have either multi-site or single-site modes of action. The resulting predicted increase in the effective life of the at risk fungicide can be large enough to be of practical relevance. The more effective the mixing partner (due to inherent activity and/or dose), the larger the reduction in selection and the larger the increase in effective life of the at-risk fungicide. 2. Adding a mixing partner while lowering the dose of the at risk fungicide reduces the selection for fungicide resistance, without compromising effective disease control. The very few studies existing suggest that the reduction in selection is more sensitive to lowering the dose of the at risk fungicide than to increasing the dose of the mixing partner. 3. Although there are very few studies, the existing evidence suggests that mixing two at risk fungicides is also a useful resistance management tactic. The aspects that have received too little attention to draw generic conclusions about the effectiveness of fungicide mixtures as resistance management strategies are as follows: (i) the relative effect of the dose of the two mixing partners on selection for fungicide resistance, (ii) the effect of mixing on the effective life of a fungicide (the time from introduction of the fungicide mode of action to the time point where the fungicide can no longer maintain effective disease control), (iii) polygenically determined resistance, (iv) mixtures of two at-risk fungicides, (v) the emergence phase of resistance evolution and the effects of mixtures during this phase, and (vi) monocyclic diseases and nonfoliar diseases. The lack of studies on these aspects of mixture use of fungicides should be a warning against overinterpreting the findings in this review. PMID- 25140386 TI - Targeting of plasminogen activator inhibitor 1 improves fibrinolytic therapy for tetracycline-induced pleural injury in rabbits. AB - Endogenous active plasminogen activator inhibitor 1 (PAI-1) was targeted in vivo with monoclonal antibodies (mAbs) that redirect its reaction with proteinases to the substrate branch. mAbs were used as an adjunct to prourokinase (single-chain [sc] urokinase [uPA]) intrapleural fibrinolytic therapy (IPFT) of tetracycline induced pleural injury in rabbits. Outcomes of scuPA IPFT (0.25 or 0.0625 mg/kg) with 0.5 mg/kg of mouse IgG or mAbs (MA-33H1F7 and MA-8H9D4) were assessed at 24 hours. Pleural fluid (PF) was collected at 0, 10, 20, and 40 minutes and 24 hours after IPFT and analyzed for plasminogen activating (PA), uPA, fibrinolytic activities, levels of total plasmin/plasminogen, alpha-macroglobulin (alphaM), mAbs/IgG antigens, free active uPA, and alphaM/uPA complexes. Anti-PAI-1 mAbs, but not mouse IgG, delivered with an eightfold reduction in the minimal effective dose of scuPA (from 0.5 to 0.0625 mg/kg), improved the outcome of IPFT (P < 0.05). mAbs and IgG were detectable in PFs at 24 hours. Compared with identical doses of scuPA alone or with IgG, treatment with scuPA and anti-PAI-1 mAbs generated higher PF uPA amidolytic and PA activities, faster formation of alphaM/uPA complexes, and slower uPA inactivation. However, PAI-1 targeting did not significantly affect intrapleural fibrinolytic activity or levels of total plasmin/plasminogen and alphaM antigens. Targeting PAI-1 did not induce bleeding, and rendered otherwise ineffective doses of scuPA able to improve outcomes in tetracycline-induced pleural injury. PAI-1-neutralizing mAbs improved IPFT by increasing the durability of intrapleural PA activity. These results suggest a novel, well-tolerated IPFT strategy that is tractable for clinical development. PMID- 25140388 TI - Potential effects of diurnal temperature oscillations on potato late blight with special reference to climate change. AB - Global climate change will have effects on diurnal temperature oscillations as well as on average temperatures. Studies on potato late blight (Phytophthora infestans) development have not considered daily temperature oscillations. We hypothesize that growth and development rates of P. infestans would be less influenced by change in average temperature as the magnitude of fluctuations in daily temperatures increases. We investigated the effects of seven constant (10, 12, 15, 17, 20, 23, and 27 degrees C) and diurnally oscillating (+/-5 and +/-10 degrees C) temperatures around the same means on number of lesions, incubation period, latent period, radial lesion growth rate, and sporulation intensity on detached potato leaves inoculated with two P. infestans isolates from clonal lineages US-8 and US-23. A four-parameter thermodynamic model was used to describe relationships between temperature and disease development measurements. Incubation and latency progression accelerated with increasing oscillations at low mean temperatures but slowed down with increasing oscillations at high mean temperatures (P < 0.005), as hypothesized. Infection efficiency, lesion growth rate, and sporulation increased under small temperature oscillations compared with constant temperatures but decreased when temperature oscillations were large. Thus, diurnal amplitude in temperature should be considered in models of potato late blight, particularly when predicting effects of global climate change on disease development. PMID- 25140389 TI - Nanoscopic poly-DNA-cleaver for breast cancer regression with induced oxidative damage. AB - A novel strategy for efficient "nanodelivery" of DNA-cleaving molecules for breast cancer regression is presented here. The synthetic methodology can be tweaked for controlled delivery and better bioavailability of effective doses of these DNA-cleaving agents through a defined self-assembled polymeric nanoarchitecture. In vitro studies in ER+ and ER- breast cancer human cell lines confirmed an efficient "nano"-delivery of DNA-cleaving molecules and indicated their capability to mediate oxidative damage to nucleobases and/or to the 2 deoxyribose moiety. Prepared E-poly-DNA-cleaver and C-poly-DNA-cleaver were found to be interacting with plasmid DNA pBR322 (pDNA) and active to cause oxidative cleavage of pDNA in the presence of ascorbic acid and H2O2. They were found to be significantly active as DNA cleaving agents in vitro and showed highly improved cancer regression in MCF-7 and MD-MB231 cancer cells compared to small molecule DNA cleaver. Surface conjugated nanoparticles were found to be more effective than noncovalent encapsulation and the small molecule agent, whereas in all the cases RCM was significantly inactive toward DNA cleavage. Blood contact complement activation properties were evaluated to gauge their likelihood to promote acute toxicity following systemic administration. The complement activation analyses together with the blood smear study confirm the feasibility of using these poly-DNA-cleavers without risk of induced immune response. PMID- 25140390 TI - Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas. AB - The circadian clock of man and mammals shows a hierarchic organization. The master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral oscillators distributed throughout the body. Rhythm generation depends on molecular clockworks based on transcriptional/translational interaction of clock genes. Numerous studies have shown that the clockwork in peripheral oscillators is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the absence of signals from the SCN. The aim of the present study is to analyze the effects of irradiation with X-rays on the clockwork of liver, adrenal and pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from transgenic mPer2(luc) mice which express luciferase under the control of the promoter of an important clock gene, Per2, and allow to study the dynamics of the molecular clockwork by bioluminometry. The preparations were cultured in a membrane-based liquid-air interface culturing system and irradiated with X-rays at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days in vitro. Oscillations persist after irradiation with X-rays. However, a dose of 50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h and in the OAEC by 6 h. Our study shows that X-rays affect the molecular clockwork in liver, pancreas and adrenal leading to phase advances. Our results confirm and extend previous studies showing a phase-advancing effect of X-rays at the level of the whole animal and single cells. PMID- 25140391 TI - The mouse liver displays daily rhythms in the metabolism of phospholipids and in the activity of lipid synthesizing enzymes. AB - The circadian system involves central and peripheral oscillators regulating temporally biochemical processes including lipid metabolism; their disruption leads to severe metabolic diseases (obesity, diabetes, etc). Here, we investigated the temporal regulation of glycerophospholipid (GPL) synthesis in mouse liver, a well-known peripheral oscillator. Mice were synchronized to a 12:12 h light-dark (LD) cycle and then released to constant darkness with food ad libitum. Livers collected at different times exhibited a daily rhythmicity in some individual GPL content with highest levels during the subjective day. The activity of GPL-synthesizing/remodeling enzymes: phosphatidate phosphohydrolase 1 (PAP-1/lipin) and lysophospholipid acyltransferases (LPLATs) also displayed significant variations, with higher levels during the subjective day and at dusk. We evaluated the temporal regulation of expression and activity of phosphatidylcholine (PC) synthesizing enzymes. PC is mainly synthesized through the Kennedy pathway with Choline Kinase (ChoK) as a key regulatory enzyme or through the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway. The PC/PE content ratio exhibited a daily variation with lowest levels at night, while ChoKalpha and PEMT mRNA expression displayed maximal levels at nocturnal phases. Our results demonstrate that mouse liver GPL metabolism oscillates rhythmically with a precise temporal control in the expression and/or activity of specific enzymes. PMID- 25140392 TI - Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction. AB - The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP) concentrations compared with those with uncomplicated pregnancy. A total of 34 pregnant women with FGR and 62 patients with uncomplicated pregnancy were included. Neopterin and CRP levels were measured at the time of diagnosis. The primary outcome of this study was to compare the neopterin and CRP levels in pregnant women with FGR and those with uncomplicated pregnancies. The secondary outcome of our study was to evaluate the correlation between fetal birth weight and maternal neopterin levels. The serum neopterin levels were significantly elevated in pregnant women with FGR (22.71 +/- 7.70 vs 19.15 +/- 8.32). However, CRP was not elevated in pregnant women with FGR (7.47 +/- 7.59 vs 5.29 +/- 3.58). These findings support the hypothesis that pregnancy with FGR is associated with a marked increase in macrophage activation and the natural immune system. PMID- 25140394 TI - SOX3 deletion in mouse and human is associated with persistence of the craniopharyngeal canal. AB - CONTEXT: SOX3 is an early developmental transcription factor involved in pituitary development. In humans, over- and underdosage of SOX3 is associated with X-linked hypopituitarism with variable phenotypes ranging from isolated GH deficiency (GHD) to panhypopituitarism, with or without mental retardation and, in most cases, with reported pituitary imaging, an ectopic/undescended posterior pituitary. PATIENT: We present a young patient with hemophilia B and developmental delay who had a 2.31-Mb deletion on Xq27 including SOX3, F9, and eight other contiguous genes. He developed GH and gonadotropin deficiency, whilst his thyroid function was in the low normal range. Magnetic resonance imaging revealed a eutopic posterior pituitary and the unusual finding of a persistent craniopharyngeal canal that has not previously been described in patients with congenital hypopituitarism. OBJECTIVE AND METHODS: To establish whether loss of SOX3 can account for the human phenotype, we examined in detail the hypothalamo pituitary region of neonatal Sox3 null mice. RESULTS: Consistent with the patient's phenotype, Sox3 null mice exhibit a ventral extension of the anterior pituitary that penetrates, and generates a mass beneath, the sphenoid bone. This suggests that the defect results from abnormal induction of Rathke's pouch, leading to a persistent connection between Rathke's pouch and the oral ectoderm. CONCLUSIONS: Our observations expand the spectrum of phenotypes observed in association with altered SOX3 dosage and may affect the approach to genetic screening. Screening for SOX3 should be advised not only for hypopituitary patients with an ectopic posterior pituitary, but also for those with a structurally normal pituitary and additional findings, including clefts and a persistent craniopharyngeal canal, with or without mental retardation. PMID- 25140395 TI - Factors associated with bone mineral density and risk of fall in Korean adults with type 2 diabetes mellitus aged 50 years and older. AB - CONTEXT: Osteoporotic fractures in subjects with diabetes mellitus (DM) carry higher mortality and morbidity. Because bone strength and minor trauma, such as a falls, are considered to be significant factors contributing to osteoporotic fractures, it is important to elucidate the associated factors with these. OBJECTIVE: This study was performed to investigate the factors associated with bone mineral density (BMD) and falls in noninstitutionalized subjects with DM aged 50 years or older. DESIGN, SETTING, AND PATIENTS: We used the database from the 2010 Fifth Korea National Health and Nutrition Examination Survey. Subjects with DM aged 50 years or older were selected and included in the data analyses. Associated factors with BMD of the femoral neck and lumbar spine and those with falls were analyzed using multiple linear regression and binary logistic regression analyses, respectively. RESULTS: Three hundred sixty-two subjects [209 males; 153 females; average age, 66.0 y (SD 8.2 y)] were included. Among the male subjects, the total body muscle mass (P < .001), daily calcium intake (P = .001), ALP levels (P = .007), and body mass index (P = .027) were significantly associated with femoral neck BMD, whereas body mass index (P = .001) and ALP levels (P = .040) were associated with lumbar spine BMD. Among the female subjects, age (P < .001), daily calcium intake (P = .011) and total body muscle mass (P = .023) were found to be significantly associated factors with femoral neck BMD, whereas age (P < .001) and body mass index (P = .012) and daily calcium intake (P = .040) were those with lumbar spine BMD. Osteoarthritis (P = .024) and total body muscle mass (P = .028) were found to be significantly associated with the risk of falls. CONCLUSIONS: Total body muscle mass was the most prominent factor predicting femoral neck BMD and risk of falls in community-dwelling elderly subjects with DM. Further investigation is required to determine their role in preventing osteoporotic fractures in diabetic subjects. PMID- 25140396 TI - Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome. AB - CONTEXT: Statins are effective cholesterol-lowering agents that reduce cardiovascular disease risk but also have pleiotropic effects that may extend to other lipid classes. OBJECTIVE: The purpose of this article was to investigate, in a post hoc analysis, the dose-dependent effects of rosuvastatin on plasma sphingolipids and phospholipids in men with the metabolic syndrome. METHODS: Subjects (n = 12) were studied in a randomized, double-blind, triple-crossover trial of a 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day) with 2-week washouts between treatments. Plasma sphingolipid profiling was determined by liquid chromatography electrospray ionization-tandem mass spectrometry. RESULTS: Rosuvastatin at 10 mg/d (R10) and 40 mg/d (R40) significantly (all P < .001 unless stated otherwise) lowered plasma cholesterol ( 34% and -42% [% change with R10 and with R40, respectively]), low-density lipoprotein cholesterol (-49% and -57%) and triglyceride (-24%, P =.03 and -42%) concentrations. Compared with placebo, R10 and R40 significantly decreased the plasma levels of total sphingolipids including those of ceramide (-33% and -37%), sphingomyelin (-27% and -31%), monohexosylceramide (-40% and -47%), dihexosylceramide (-31% and -34%), and trihexosylceramide (-29% and -31%), and GM3 gangliosides (-29% and -26%), lysophosphatidylcholine (-32% and -37%), alkylphosphatidylcholine (-19% and -19%), phosphatidylcholine (-17% and -19%), alkenylphosphatidylcholine (plasmalogen) (-20% and -22%), alkylphosphatidylethanolamine (-20%, P =.008 and -24%, P =.02), alkenylphosphatidylethanolamine (plasmalogen) (-24%, P =.003 and -23%, P =.007), phosphatidylglycerol (-24%, P =.07, -31%, P =.046), and phosphatidylinositol ( 34% and -40%). No significant changes were found with phosphatidylethanolamine and phosphatidylserine. Significant dose effects were found with the majority of the plasma sphingolipids, whereas only phosphatidylcholine, lysophosphatidylcholine, alkylphosphatidylcholine, alkenylphosphatidylcholine (plasmalogen), and phosphatidylinositol had significant dose effects. Similar changes were found with plasma sphingolipids when results were normalized to the total phosphatidylcholine concentration. CONCLUSIONS: Rosuvastatin dose dependently lowers plasma sphingolipids and phospholipids, independent of low density lipoprotein lowering, in men with the metabolic syndrome. PMID- 25140393 TI - mRNA-binding protein TIA-1 reduces cytokine expression in human endometrial stromal cells and is down-regulated in ectopic endometrium. AB - BACKGROUND: Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3'-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. OBJECTIVE: The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. METHODS: Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF alpha, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL 6 or TNF-alpha expression in these cells. RESULTS: We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-alpha increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-alpha expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-alpha expression. CONCLUSIONS: Endometrial TIA-1 is regulated throughout the menstrual cycle, TIA-1 modulates the expression of immune factors in endometrial cells, and downregulation of TIA-1 may contribute to the pathogenesis of endometriosis. PMID- 25140397 TI - Plasma parathyroid hormone is associated with vascular dementia and cerebral hyperintensities in two community-based cohorts. AB - CONTEXT: In diseases with increased PTH such as hyperparathyroidism and chronic renal failure, dementia is common. Little is known of PTH and dementia in the community. OBJECTIVE: We sought to investigate relations between PTH, clinical dementia and cerebral micro-vascular disease. SETTING AND DESIGN: The Uppsala Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995; followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community based. PARTICIPANTS AND MAIN OUTCOME MEASURE: In the ULSAM study of 998 men (age 71) the association between PTH and dementia was investigated. In the PIVUS study of 406 men and women (age 70) the relation between PTH and magnetic resonance imaging signs of cerebral small vascular disease was investigated. RESULTS: During followup, 56 individuals were diagnosed with vascular, 91 with Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH was associated with vascular dementia (hazard ratio per 1 SD increase of PTH, 1.41; P < .01), but not with other dementias. The top tertile of PTH accounted for 18.5% of the population-attributable risk for vascular dementia, exceeding all other risk factors. In linear regression analysis in PIVUS, PTH was associated with increasing white matter hyperintensities (WMHI), reflecting increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31 higher category of WMHI; P = .016). All models were adjusted for vascular risk factors and mineral metabolism. CONCLUSIONS: In two community-based samples, PTH predicted clinically diagnosed vascular dementia as well as neuroimaging indices of cerebral small vessel disease. Our data suggest a role for PTH in the development of vascular dementia. PMID- 25140398 TI - Approach to the patient: transgender youth: endocrine considerations. AB - Compelling studies have demonstrated that "gender identity"--a person's inner sense of self as male, female, or occasionally a category other than male or female--is not simply a psychosocial construct, but likely reflects a complex interplay of biological, environmental, and cultural factors. An increasing number of preadolescents and adolescents, identifying as "transgender" (a transient or persistent identification with a gender different from their "natal gender"--ie, the gender that is assumed based on the physical sex characteristics present at birth), are seeking medical services to enable the development of physical characteristics consistent with their affirmed gender. Such services, including the use of agents to block endogenous puberty at Tanner stage 2 and subsequent use of cross-sex hormones, are based on longitudinal studies demonstrating that those individuals who were first identified as gender dysphoric in early or middle childhood and who still meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. Furthermore, onset of puberty in transgender youth is often accompanied by increased "gender dysphoria"--clinically significant distress related to the incongruence between one's affirmed gender and one's "assigned (or natal) gender." Studies have shown that such distress may be ameliorated by a "gender affirming" model of care. Although endocrinologists are familiar with concerns surrounding gender identity in patients with disorders of sex development, many providers are unfamiliar with the approach to the evaluation and management of transgender youth without a disorder of sex development. The goals of this article are to review studies that shed light on the biological underpinnings of gender identity, the epidemiology and natural history of transgenderism, current clinical practice guidelines for transgender youth, and limitations and challenges to optimal care. Prospective cohort studies focused on long-term safety and efficacy are needed to optimize medical and mental health care for transgender youth. PMID- 25140399 TI - TGF-beta1 downregulates StAR expression and decreases progesterone production through Smad3 and ERK1/2 signaling pathways in human granulosa cells. AB - CONTEXT: Regulation of progesterone production in granulosa cells is important for normal reproductive functions. Steroidogenic acute regulatory protein (StAR) is recognized as the key regulatory protein involved in the rate-limiting step of steroidogenesis. TGF-beta1 protein is detected in human follicular fluid, and TGF beta1 and its receptors are expressed in human granulosa cells. However, the functional role of TGF-beta1 in the regulation of StAR expression and progesterone production in human granulosa cells remains unknown. OBJECTIVE: Our objective was to investigate the effects of TGF-beta1 on StAR expression and progesterone production in human granulosa cells. DESIGN AND SETTING: SVOG cells are human granulosa cells that were obtained from women undergoing in vitro fertilization and immortalized with SV40 large T antigen. SVOG cells were used to investigate the effects of TGF-beta1 on StAR expression and progesterone production at an academic research center. MAIN OUTCOME MEASURES: Levels of mRNA and protein were examined by RT-qPCR and western blotting, respectively. The accumulation levels of progesterone were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: TGF-beta1 treatment downregulated StAR expression and decreased progesterone production. The suppressive effects of TGF-beta1 on StAR expression and progesterone production were abolished by the inhibition of TGF beta type I receptor. In addition, treatment with TGF-beta1 activated the Smad2/3 and ERK1/2 signaling pathways. The inhibition of the Smad3 and ERK1/2 signaling pathways attenuated the TGF-beta1-induced downregulation of StAR expression and progesterone production. CONCLUSION: TGF-beta1 downregulated StAR expression and decreased progesterone production by activating the Smad3 and ERK1/2 signaling pathways in human granulosa cells. PMID- 25140400 TI - Elimination of pain and improvement of exercise capacity in Camurati-Engelmann disease with losartan. AB - BACKGROUND: Camurati-Engelmann disease (CED) is a rare disorder, with approximately 250 described cases in the literature. Treatment options are limited and have been suboptimal so far. PATIENT AND METHODS: A prepubertal girl aged 9 years was diagnosed with CED. Treatment with losartan was initiated at a daily dose of 0.75 mg/kg. Over a period of 12 weeks, the dose was gradually increased to 1.0 mg/kg/d. The patient was reviewed in clinic regularly and underwent thorough clinical assessments 9, 17, and 38 months after treatment initiation. RESULTS: The patient experienced marked clinical improvements with losartan. In particular, losartan treatment led to the complete elimination of the previously severe and incapacitating pain, with an increased ability to walk and perform physical activities. There was also a considerable improvement in body composition with increased lean and adipose tissue. Notably, the improvement in fat deposition had not been previously observed with other treatments in CED. Hematology, liver, and renal function tests were within normal ranges at presentation and remained so over the course of treatment. CONCLUSIONS: In light of our findings, losartan may be a useful option in CED management. PMID- 25140402 TI - Less myostatin and more lean mass in large-born infants from nondiabetic mothers. AB - CONTEXT AND OBJECTIVE: Sexagenarians born large are at lower risk for type 2 diabetes than those born small, a key feature of their body composition being a higher muscle mass, which explains their higher body mass index and also their lower fat-to-lean-mass ratio. Myogenesis is completed in early infancy under the inhibitory control of myostatin. We tested whether large-born infants from nondiabetic mothers develop an early surplus of lean mass while having a lower myostatinemia. Design, Methods, Study Participants, and Main Outcomes: In a longitudinal study (0-4 mo), we compared the body composition and endocrine markers (fasting glucose, insulin, IGF-1, high molecular weight adiponectin) of breast-fed appropriate- vs large-for-gestational-age infants (n = 125) from nondiabetic mothers. Circulating myostatin concentrations were assayed after collection of the above-mentioned data. SETTING: The study was conducted at the University Hospital for Women and Children. INTERVENTION: There were no interventions. RESULTS: Between 0-4 months, large-for-gestational-age infants switched from an adipose to a lean body composition (due to a nearly 20% excess of lean mass) and to an insulin-sensitive and hyperadiponectinemic state while having low IGF-1 concentrations and the lowest myostatinemia hitherto reported in the human (all between P <= .01 and P <= .0001). CONCLUSION: Large-born infants from nondiabetic mothers were found to combine a low myostatinemia with an excess of lean mass. The fetal-neonatal control of myostatinemia deserves further attention because it could become a target of interventions that aim at reducing the risk for diabetes in later life by augmenting myogenesis in early life. PMID- 25140401 TI - Functional analysis of novel genetic variation in the thyroid hormone activating type 2 deiodinase. AB - CONTEXT: Thyroid hormones (TH) are important for normal brain development and abnormal TH regulation in the brain results in neurocognitive impairments. The type 2 deiodinase (D2) is important for local TH control in the brain by generating the active hormone T3 from its precursor T4. Dysfunction of D2 likely results in a neurocognitive phenotype. No mutations in D2 have been reported yet. OBJECTIVE: The objective of the study was to identify D2 mutations in patients with intellectual disability and to test their functional consequences. DESIGN, SETTING, AND PATIENTS: The patients were selected from the multicenter Thyroid Origin of Psychomotor Retardation study, which is a cohort of 946 subjects with unexplained intellectual disability. Based on characteristic serum TH values, the coding region of the DIO2 gene was sequenced in 387 patients. Functional consequences were assessed by in vitro D2 assays or intact cell metabolism studies using cells transfected with wild-type or mutant D2. RESULTS: Sequence analysis revealed two heterozygous mutations: c.11T>A (p.L4H) in three subjects and c.305C>T (p.T102I) in one subject. Sequence analysis of family members revealed several carriers, but no segregation was observed with thyroid parameters or neurocognitive phenotype. Extensive tests with different in vitro D2 assays did not show differences between wild-type and mutant D2. CONCLUSION: This study describes the identification and functional consequences of novel genetic variation in TH activating enzyme D2. Family studies and functional tests suggest that these variants do not underlie the neurocognitive impairment. Altogether our data provide evidence of the existence of rare but apparently harmless genetic variants of D2. PMID- 25140403 TI - Loss of sex difference in high-density lipoprotein cholesterol in diabetic women during acute stress. AB - CONTEXT: The gender gap in high-density lipoprotein cholesterol (HDL-C) is well documented in health and also maintained in diverse chronic conditions, including menopause and diabetes. The mechanism for this difference in HDL-C and its regulation is not well understood. We evaluated whether this gender gap is maintained during acute stress. SETTING AND DESIGN: Diabetic patients with metabolic decompensation (n=179) were studied in the fasting state within 24 hours of admission to hospital, and again at outpatient follow-up. Fasting lipids and measures of glycemic control were evaluated on both occasions. The population was predominately minority, 78% Hispanic or African American. RESULTS: During admission, fasting lipid concentrations were not different in women (W) (n = 88) and men (M) (n = 91); serum total cholesterol (total-C), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and HDL-C were similar. Glycemic control was also similar; hemoglobin A1c (A1C) and serum glucose at presentation to hospital were not different in men and women. Compared with a subset of patients with pre-admission data (W, 35; M, 24), a decline of HDL-C was observed, greater in women (P = .005). At outpatient follow-up after admission, median duration approximately 4 months in each group (P = .39), changes in TG, LDL-C, and total-C from baseline admission were not different in men and women. In contrast, whereas HDL-C increased in both groups, the increase (median [interquartile range]) was significantly greater in women, 11 (4, 23) vs 6 (-1, 15) mg/dL (P < .003). This larger increase restored the gender gap in fasting HDL-C, 48 (39, 61) and 41 (36, 49) mg/dL in women and men at follow-up (P < .002). A1C improved similarly in each group. CONCLUSIONS: The sex difference in HDL-C levels is lost at time of admission to hospital in patients with diabetes, and returns when acute stress has resolved. These results raise the possibility that recurrent episodes of acute stress may lead to cumulative loss of the HDL-C advantage in women. PMID- 25140404 TI - Central hypoadrenalism. AB - CONTEXT: Central hypoadrenalism is a frequent complication of pituitary and hypothalamic pathology and is associated with increased morbidity and mortality. Optimal exogenous glucocorticoid use is dependent on the use of appropriate diagnostic tests and careful assessment of the clinical response to glucocorticoid replacement therapy. EVIDENCE ACQUISITION: A PubMed search for the terms central hypoadrenalism, ACTH deficiency, glucocorticoid suppression, and glucocorticoid replacement was conducted; the papers identified and the references listed were used to build a reference list. EVIDENCE SYNTHESIS: The published literature was assessed to present a summary of the available evidence with regard to etiology, diagnosis, and treatment of central hypoadrenalism. CONCLUSIONS: A functional hypothalamic pituitary adrenal axis is essential for normal health and life expectancy; its complexity presents challenges to the clinician in the identification of patients and in the maintenance of such patients in a glucocorticoid-sufficient state. The most common cause of central hypoadrenalism remains exogenous glucocorticoid use. Further research in this field should be directed toward disease prevention by minimizing glucocorticoid exposure and toward the identification of a biomarker for glucocorticoid sufficiency that will aid clinicians in optimizing treatment. PMID- 25140405 TI - Choroidal tuberculoma showing paradoxical worsening in a patient with miliary TB. AB - Tuberculosis (TB) remains an important public health problem worldwide. Ocular involvement in patients with systemic TB has traditionally been considered uncommon. Diagnosing ocular TB is challenging and often delayed, especially in the absence of pulmonary signs or symptoms typical of TB. Here we describe a case of paradoxical reaction after antituberculosis therapy in an immunocompetent patient with ocular TB. PMID- 25140406 TI - Differentiated availability of geochemical mercury pools controls methylmercury levels in estuarine sediment and biota. AB - Neurotoxic methylmercury (MeHg) formed from inorganic divalent mercury (Hg(II)) accumulates in aquatic biota and remains at high levels worldwide. It is poorly understood to what extent different geochemical Hg pools contribute to these levels. Here we report quantitative data on MeHg formation and bioaccumulation, in mesocosm water-sediment model ecosystems, using five Hg(II) and MeHg isotope tracers simulating recent Hg inputs to the water phase and Hg stored in sediment as bound to natural organic matter or as metacinnabar. Calculations for an estuarine ecosystem suggest that the chemical speciation of Hg(II) solid/adsorbed phases control the sediment Hg pool's contribution to MeHg, but that input of MeHg from terrestrial and atmospheric sources bioaccumulates to a substantially greater extent than MeHg formed in situ in sediment. Our findings emphasize the importance of MeHg loadings from catchment runoff to MeHg content in estuarine biota and we suggest that this contribution has been underestimated. PMID- 25140408 TI - Chronic alcohol administration causes expression of calprotectin and RAGE altering the distribution of zinc ions in mouse testis. AB - Several studies reported that chronic alcohol consumption alters the intestinal mucosa barrier, and subsequent entrance of endotoxins into the bloodstream. In many tissues endotoxin exposure causes the expression of calprotectin (CP) and the receptor for advanced glycation -end products (RAGE). In this study we investigated whether chronic alcohol administration causes expression of CP and RAGE in mouse testis. The distribution of free and loosely bound Zn(2+) (FLB Zn(2+)) in the testicular tissues was also evaluated. Alcohol-induced testicular damage was documented by measuring testosterone blood levels and by light and electron microscope studies. Twenty mice were treated daily for three weeks with 3.0 g/kg of a 25% solution of alcohol. Ten mice were treated in the same period of time with a solution of maltose dextrins, isocaloric to alcohol. Twenty untreated mice were used as controls. Alcohol treated mice showed diffuse expression of CP and RAGE in the interstitial cells. RAGE was found also in the basal compartment of the seminiferous tubules. Depletion of FLB-Zn(2+) was observed in the adluminal compartment of the seminiferous tubules. Expression of CP and RAGE was not found in control mice and maltose dextrin treated mice. Our results indicated novel mechanisms by which alcohol acts in testis. Indeed, CP and RAGE may cause the generation of oxidants and inflammatory mediators, with negative impact on testicular functions. Depletion of FLB-Zn(2+) may contribute to the dysregulation of spermatogenesis. PMID- 25140407 TI - Patient Navigation in a Colorectal Cancer Screening Program. AB - CONTEXT: Colorectal cancer (CRC) is the second leading cause of cancer death among cancers affecting both men and women in the United States. The Centers for Disease Control and Prevention's Colorectal Cancer Control Program (CRCCP) supports both direct clinical screening services (screening provision) and activities to promote screening at the population level (screening promotion). OBJECTIVE: The purpose of this study was to characterize patient navigation (PN) programs for screening provision and promotion for the first 1 to 2 years of program funding. PARTICIPANTS: We conducted a cross-sectional survey of the 29 CRCCP grantees (25 states and 4 tribal organizations) and 14 in-depth interviews to assess program implementation. MAIN OUTCOME MEASURES: The survey and interview guide collected information on CRC screening provision and promotion activities and PN, including the structure of the PN program, characteristics of the navigators, funding mechanism, and navigators' activities. RESULTS: Twenty-four of 28 CRCCP grantees of the survey used PN for screening provision whereas 18 grantees used navigation for screening promotion. Navigators were often trained in nursing or public health. Navigation activities were similar for both screening provision and promotion, and common tasks included assessing and responding to patient barriers to screening, providing patient education, and scheduling appointments. For screening provision, activities centered on making reminder calls, educating patients on bowel preparation for colonoscopies, and tracking patients for completion of the tests. Navigation may influence screening quality by improving patients' bowel preparation for colonoscopies. CONCLUSIONS: Our study provides insights into PN across a federally funded CRC program. Results suggest that PN activities may be instrumental in recruiting people into cancer screening and ensuring completed screening and follow-up. PMID- 25140409 TI - The effect of melatonin on procarbazine induced testicular toxicity on rats. AB - Procarbazine (P) is an effective chemotherapeutic drug especially used in lymphoma treatment; however testicular toxicity is a limiting factor. Various ways of treatment were tried to preserve testicular function including hormonal treatment, antioxidant treatment, and sperm cryopreservation but resulted with low rates of satisfaction. Procarbazine is a well known agent causing sterility even in the first doses of chemotherapy. Antioxidants such as N acetylcysteine and ascorbate have been used for protective purposes and were very successful. Melatonin (M) is another powerful antioxidant and we aimed to use M for the protection of P induced testicular toxicity in this study. Procarbazine was given peroral by gavage once a week at a dose of 62.5 mg/kg/week for 4 weeks (total dose: 250 mg/kg) (P group) and in procarbazine + melatonin (PM) group, 10 mg/kg melatonin was intraperitoneally administered daily for five days a week for 4 weeks (total 20 days). The experiment ended at day 90. In the P and PM groups the testicle width, length, and weight, sperm A and sperm AB properties (Sperm A: sperms straight line progressive, Sperm B: sperms straight slow progressive, Sperm AB: Sperm A + Sperm B), spermatogonia, Sertoli cells, seminiferous tubule, and germinative layer thickness were lowered as compared with the control group. However, there were no significant differences between the P and PM groups in regard to these parameters. Melatonin preserved Sertoli cell and spermatogonia function. The testosterone and follicle-stimulating hormone (FSH) levels were also preserved. Melatonin significantly decreased malondialdehyde (MDA) levels and preserved the antioxidant enzyme levels such as glutathione peroxidase (GPx) and nitrite nitrate (NO2-/NO3-). Melatonin may protect testicular functions in P treated patients and is open to consideration during chemotherapy since it appears to be without any side effects. PMID- 25140410 TI - Reversible modulation of orbital occupations via an interface-induced polar state in metallic manganites. AB - The breaking of orbital degeneracy on a transition metal cation and the resulting unequal electronic occupations of these orbitals provide a powerful lever over electron density and spin ordering in metal oxides. Here, we use ab initio calculations to show that reversibly modulating the orbital populations on Mn atoms can be achieved at ferroelectric/manganite interfaces by the presence of ferroelectric polarization on the nanoscale. The change in orbital occupation can be as large as 10%, greatly exceeding that of bulk manganites. This reversible orbital splitting is in large part controlled by the propagation of ferroelectric polar displacements into the interfacial region, a structural motif absent in the bulk and unique to the interface. We use epitaxial thin film growth and scanning transmission electron microscopy to verify this key interfacial polar distortion and discuss the potential of reversible control of orbital polarization via nanoscale ferroelectrics. PMID- 25140411 TI - Two-center noninteger-n overlap, Coulomb, and kinetic energy integrals by numerical contour integration. AB - Numerical contour integration accurately evaluates two-center overlap, Coulomb, and kinetic energy integrals involving noninteger-n Slater-type orbitals. PMID- 25140412 TI - Frozen in beta. PMID- 25140413 TI - Work and tension: new evidence that adherent cells of the same area do the same work independent of stiffness and focal adhesions. PMID- 25140414 TI - All that jazz coming out of my ears. PMID- 25140415 TI - Evaluation of fluorophores to label SNAP-tag fused proteins for multicolor single molecule tracking microscopy in live cells. AB - Single-molecule tracking has become a widely used technique for studying protein dynamics and their organization in the complex environment of the cell. In particular, the spatiotemporal distribution of membrane receptors is an active field of study due to its putative role in the regulation of signal transduction. The SNAP-tag is an intrinsically monovalent and highly specific genetic tag for attaching a fluorescent label to a protein of interest. Little information is currently available on the choice of optimal fluorescent dyes for single-molecule microscopy utilizing the SNAP-tag labeling system. We surveyed 6 green and 16 red excitable dyes for their suitability in single-molecule microscopy of SNAP-tag fusion proteins in live cells. We determined the nonspecific binding levels and photostability of these dye conjugates when bound to a SNAP-tag fused membrane protein in live cells. We found that only a limited subset of the dyes tested is suitable for single-molecule tracking microscopy. The results show that a careful choice of the dye to conjugate to the SNAP-substrate to label SNAP-tag fusion proteins is very important, as many dyes suffer from either rapid photobleaching or high nonspecific staining. These characteristics appear to be unpredictable, which motivated the need to perform the systematic survey presented here. We have developed a protocol for evaluating the best dyes, and for the conditions that we evaluated, we find that Dy 549 and CF 640 are the best choices tested for single molecule tracking. Using an optimal dye pair, we also demonstrate the possibility of dual-color single-molecule imaging of SNAP-tag fusion proteins. This survey provides an overview of the photophysical and imaging properties of a range of SNAP-tag fluorescent substrates, enabling the selection of optimal dyes and conditions for single-molecule imaging of SNAP-tagged fusion proteins in eukaryotic cell lines. PMID- 25140416 TI - An active oscillator model describes the statistics of spontaneous otoacoustic emissions. AB - Even in the absence of external stimulation, the cochleas of most humans emit very faint sounds below the threshold of hearing, sounds that are known as spontaneous otoacoustic emissions. They are a signature of the active amplification mechanism in the cochlea. Emissions occur at frequencies that are unique for an individual and change little over time. The statistics of a population of ears exhibit characteristic features such as a preferred relative frequency distance between emissions (interemission intervals). We propose a simplified cochlea model comprising an array of active nonlinear oscillators coupled both hydrodynamically and viscoelastically. The oscillators are subject to a weak spatial disorder that lends individuality to the simulated cochlea. Our model captures basic statistical features of the emissions: distributions of 1), emission frequencies; 2), number of emissions per ear; and 3), interemission intervals. In addition, the model reproduces systematic changes of the interemission intervals with frequency. We show that the mechanism for the preferred interemission interval in our model is the occurrence of synchronized clusters of oscillators. PMID- 25140417 TI - Geometry regulates traction stresses in adherent cells. AB - Cells generate mechanical stresses via the action of myosin motors on the actin cytoskeleton. Although the molecular origin of force generation is well understood, we currently lack an understanding of the regulation of force transmission at cellular length scales. Here, using 3T3 fibroblasts, we experimentally decouple the effects of substrate stiffness, focal adhesion density, and cell morphology to show that the total amount of work a cell does against the substrate to which it is adhered is regulated by the cell spread area alone. Surprisingly, the number of focal adhesions and the substrate stiffness have little effect on regulating the work done on the substrate by the cell. For a given spread area, the local curvature along the cell edge regulates the distribution and magnitude of traction stresses to maintain a constant strain energy. A physical model of the adherent cell as a contractile gel under a uniform boundary tension and mechanically coupled to an elastic substrate quantitatively captures the spatial distribution and magnitude of traction stresses. With a single choice of parameters, this model accurately predicts the cell's mechanical output over a wide range of cell geometries. PMID- 25140418 TI - Single-molecule tracking of inositol trisphosphate receptors reveals different motilities and distributions. AB - Puffs are local Ca(2+) signals that arise by Ca(2+) liberation from the endoplasmic reticulum through the concerted opening of tightly clustered inositol trisphosphate receptors/channels (IP3Rs). The locations of puff sites observed by Ca(2+) imaging remain static over several minutes, whereas fluorescence recovery after photobleaching (FRAP) experiments employing overexpression of fluorescently tagged IP3Rs have shown that the majority of IP3Rs are freely motile. To address this discrepancy, we applied single-molecule imaging to locate and track type 1 IP3Rs tagged with a photoswitchable fluorescent protein and expressed in COS-7 cells. We found that ~ 70% of the IP3R1 molecules were freely motile, undergoing random walk motility with an apparent diffusion coefficient of ~ 0.095 MUm s(-1), whereas the remaining molecules were essentially immotile. A fraction of the immotile IP3Rs were organized in clusters, with dimensions (a few hundred nanometers across) comparable to those previously estimated for the IP3R clusters underlying functional puff sites. No short-term (seconds) changes in overall motility or in clustering of immotile IP3Rs were apparent following activation of IP3/Ca(2+) signaling. We conclude that stable clusters of small numbers of immotile IP3Rs may underlie local Ca(2+) release sites, whereas the more numerous motile IP3Rs appear to be functionally silent. PMID- 25140419 TI - Quantitation of malaria parasite-erythrocyte cell-cell interactions using optical tweezers. AB - Erythrocyte invasion by Plasmodium falciparum merozoites is an essential step for parasite survival and hence the pathogenesis of malaria. Invasion has been studied intensively, but our cellular understanding has been limited by the fact that it occurs very rapidly: invasion is generally complete within 1 min, and shortly thereafter the merozoites, at least in in vitro culture, lose their invasive capacity. The rapid nature of the process, and hence the narrow time window in which measurements can be taken, have limited the tools available to quantitate invasion. Here we employ optical tweezers to study individual invasion events for what we believe is the first time, showing that newly released P. falciparum merozoites, delivered via optical tweezers to a target erythrocyte, retain their ability to invade. Even spent merozoites, which had lost the ability to invade, retain the ability to adhere to erythrocytes, and furthermore can still induce transient local membrane deformations in the erythrocyte membrane. We use this technology to measure the strength of the adhesive force between merozoites and erythrocytes, and to probe the cellular mode of action of known invasion inhibitory treatments. These data add to our understanding of the erythrocyte-merozoite interactions that occur during invasion, and demonstrate the power of optical tweezers technologies in unraveling the blood-stage biology of malaria. PMID- 25140420 TI - Mechanical detection of a long-range actin network emanating from a biomimetic cortex. AB - Actin is ubiquitous globular protein that polymerizes into filaments and forms networks that participate in the force generation of eukaryotic cells. Such forces are used for cell motility, cytokinesis, and tissue remodeling. Among those actin networks, we focus on the actin cortex, a dense branched network beneath the plasma membrane that is of particular importance for the mechanical properties of the cell. Here we reproduce the cellular cortex by activating actin filament growth on a solid surface. We unveil the existence of a sparse actin network that emanates from the surface and extends over a distance that is at least 10 times larger than the cortex itself. We call this sparse actin network the "actin cloud" and characterize its mechanical properties with optical tweezers. We show, both experimentally and theoretically, that the actin cloud is mechanically relevant and that it should be taken into account because it can sustain forces as high as several picoNewtons (pN). In particular, it is known that in plant cells, actin networks similar to the actin cloud have a role in positioning the nucleus; in large oocytes, they play a role in driving chromosome movement. Recent evidence shows that such networks even prevent granule condensation in large cells. PMID- 25140421 TI - Actin-myosin spatial patterns from a simplified isotropic viscoelastic model. AB - F-actin networks are involved in cell mechanical processes ranging from motility to endocytosis. The mesoscale architecture of assemblies of individual F-actin polymers that gives rise to micrometer-scale rheological properties is poorly understood, despite numerous in vivo and vitro studies. In vitro networks have been shown to organize into spatial patterns when spatially confined, including dense spherical shells inside spherical emulsion droplets. Here we develop a simplified model of an isotropic, compressible, viscoelastic material continually assembling and disassembling. We demonstrate that spherical shells emerge naturally when the strain relaxation rate (corresponding to internal network reorganization) is slower than the disassembly rate (corresponding to F-actin depolymerization). These patterns are consistent with recent experiments, including a collapse of shells to a central high-density focus of F-actin when either assembly or disassembly is reduced with drugs. Our results demonstrate how complex spatio-temporal patterns can emerge without spatially distributed force generation, polar alignment of F-actin polymers, or spatially nonuniform regulation of F-actin by upstream biochemical networks. PMID- 25140422 TI - Osmotic pressure in a bacterial swarm. AB - Using Escherichia coli as a model organism, we studied how water is recruited by a bacterial swarm. A previous analysis of trajectories of small air bubbles revealed a stream of fluid flowing in a clockwise direction ahead of the swarm. A companion study suggested that water moves out of the agar into the swarm in a narrow region centered ~ 30 MUm from the leading edge of the swarm and then back into the agar (at a smaller rate) in a region centered ~ 120 MUm back from the leading edge. Presumably, these flows are driven by changes in osmolarity. Here, we utilized green/red fluorescent liposomes as reporters of osmolarity to verify this hypothesis. The stream of fluid that flows in front of the swarm contains osmolytes. Two distinct regions are observed inside the swarm near its leading edge: an outer high-osmolarity band (~ 30 mOsm higher than the agar baseline) and an inner low-osmolarity band (isotonic or slightly hypotonic to the agar baseline). This profile supports the fluid-flow model derived from the drift of air bubbles and provides new (to our knowledge) insights into water maintenance in bacterial swarms. High osmotic pressure at the leading edge of the swarm extracts water from the underlying agar and promotes motility. The osmolyte is of high molecular weight and probably is lipopolysaccharide. PMID- 25140424 TI - Orientational ordering of carotenoids in myelin membranes resolved by polarized Raman microspectroscopy. AB - We study orientational ordering of membrane compounds in the myelinated nerve fiber by means of polarized Raman microspectroscopy. The theory of orientational distribution functions was adapted to live-cell measurements. The obtained orientational distribution functions of carotenoids and lipid acyl chain clearly indicated a predominantly radial-like orientation in membranes of the myelin. Two dimensional Raman images, made under optimal polarization of incident laser beam, corroborated the proposed carotenoid orientation within the bilayer. Experimental data suggested the tilted orientation of both carotenoid polyenic and lipid acyl chains. The values of maximum tilt angles were similar, with possible implication of carotenoid-induced ordering effect on lipid acyl chains, and hence change of myelin membrane properties. This study stages carotenoids of the nerve as possible mediators of excitation and leverages underlying activity-dependent membrane reordering. PMID- 25140423 TI - Interplay of packing and flip-flop in local bilayer deformation. How phosphatidylglycerol could rescue mitochondrial function in a cardiolipin deficient yeast mutant. AB - In a previous work, we have shown that a spatially localized transmembrane pH gradient, produced by acid micro-injection near the external side of cardiolipin containing giant unilamellar vesicles, leads to the formation of tubules that retract after the dissipation of this gradient. These tubules have morphologies similar to mitochondrial cristae. The tubulation effect is attributable to direct phospholipid packing modification in the outer leaflet, that is promoted by protonation of cardiolipin headgroups. In this study, we compare the case of cardiolipin-containing giant unilamellar vesicles with that of giant unilamellar vesicles that contain phosphatidylglycerol (PG). Local acidification also promotes formation of tubules in the latter. However, compared with cardiolipin containing giant unilamellar vesicles the tubules are longer, exhibit a visible pearling, and have a much longer lifetime after acid micro-injection is stopped. We attribute these differences to an additional mechanism that increases monolayer surface imbalance, namely inward PG flip-flop promoted by the local transmembrane pH gradient. Simulations using a fully nonlinear membrane model as well as geometrical calculations are in agreement with this hypothesis. Interestingly, among yeast mutants deficient in cardiolipin biosynthesis, only the crd1-null mutant, which accumulates phosphatidylglycerol, displays significant mitochondrial activity. Our work provides a possible explanation of such a property and further emphasizes the salient role of specific lipids in mitochondrial function. PMID- 25140425 TI - Membrane interactions of phylloseptin-1, -2, and -3 peptides by oriented solid state NMR spectroscopy. AB - Phylloseptin-1, -2, and -3 are three members of the family of linear cationic antimicrobial peptides found in tree frogs. The highly homologous peptides encompass 19 amino acids, and only differ in the amino acid composition and charge at the six most carboxy-terminal residues. Here, we investigated how such subtle changes are reflected in their membrane interactions and how these can be correlated to their biological activities. To this end, the three peptides were labeled with stable isotopes, reconstituted into oriented phospholipid bilayers, and their detailed topology determined by a combined approach using (2)H and (15)N solid-state NMR spectroscopy. Although phylloseptin-2 and -3 adopt perfect in-plane alignments, the tilt angle of phylloseptin-1 deviates by 8 degrees probably to assure a more water exposed localization of the lysine-17 side chain. Furthermore, different azimuthal angles are observed, positioning the amphipathic helices of all three peptides with the charged residues well exposed to the water phase. Interestingly, our studies also reveal that two orientation-dependent (2)H quadrupolar splittings from methyl-deuterated alanines and one (15)N amide chemical shift are sufficient to unambiguously determine the topology of phylloseptin-1, where quadrupolar splittings close to the maximum impose the most stringent angular restraints. As a result of these studies, a strategy is proposed where the topology of a peptide structure can be determined accurately from the labeling with (15)N and (2)H isotopes of only a few amino acid residues. PMID- 25140426 TI - Influenza A matrix protein M1 multimerizes upon binding to lipid membranes. AB - The matrix protein M1 plays a pivotal role in the budding of influenza virus from the plasma membrane (PM) of infected cells. This protein interacts with viral genetic material and envelope proteins while binding to the inner leaflet of the PM. Its oligomerization is therefore closely connected to the assembly of viral components and the formation of new virions. Of interest, the molecular details of M1 interaction with lipids and other viral proteins are far from being understood, and it remains to be determined whether the multimerization of M1 is affected by its binding to the PM and interaction with its components. To clarify the connection between M1 oligomerization and binding to lipid membranes, we applied a combination of several quantitative microscopy approaches. First, we used number and brightness (N&B) microscopy to characterize protein multimerization upon interaction with the PM of living cells. Second, we used controlled biophysical models of the PM (i.e., supported bilayers) to delve into the details of M1-lipid and M1-M1 interactions by employing a combination of raster image correlation spectroscopy (RICS), fluorescence correlation spectroscopy (FCS), and atomic force microscopy (AFM). Our results show that M1 oligomer formation is strongly enhanced by membrane binding and does not necessarily require the presence of other viral proteins. Furthermore, we propose a specific model to explain M1 binding to the lipid bilayer and the formation of multimers. PMID- 25140427 TI - Temperature and electrolyte optimization of the alpha-hemolysin latch sensing zone for detection of base modification in double-stranded DNA. AB - The latch region of the wild-type protein pore alpha-hemolysin (alpha-HL) constitutes a sensing zone for individual abasic sites (and furan analogs) in double-stranded DNA (dsDNA). The presence of an abasic site or furan within a DNA duplex, electrophoretically captured in the alpha-HL vestibule and positioned at the latch region, can be detected based on the current blockage prior to duplex unzipping. We investigated variations in blockage current as a function of temperature (12-35 degrees C) and KCl concentration (0.15-1.0 M) to understand the origin of the current signature and to optimize conditions for identifying the base modification. In 1 M KCl solution, substitution of a furan for a cytosine base in the latch region results in an ~ 8 kJ mol(-1) decrease in the activation energy for ion transport through the protein pore. This corresponds to a readily measured ~ 2 pA increase in current at room temperature. Optimal resolution for detecting the presence of a furan in the latch region is achieved at lower KCl concentrations, where the noise in the measured blockage current is significantly lower. The noise associated with the blockage current also depends on the stability of the duplex (as measured from the melting temperature), where a greater noise in the measured blockage current is observed for less stable duplexes. PMID- 25140428 TI - Azobenzene photoisomerization-induced destabilization of B-DNA. AB - Molecular photoswitches provide a promising way for selective regulation of nanoscaled biological systems. It has been shown that conformational changes of azobenzene, one of the widely used photoswitches, can be used to reversibly control DNA duplex formation. Here, we investigate the conformational response of DNA upon azobenzene binding and isomerization, using a threoninol linker that has been experimentally investigated recently. To this end, nonequilibrium molecular dynamics simulations are carried out using a switching potential describing the photoinduced isomerization. Attachment of azobenzene leads to a distortion of the DNA helical conformation that is similar for the trans and cis forms. However, the trans form is stabilized by favorable stacking interactions whereas the cis form is found to remain flipped out of the basepair-stacked position. Multiple azobenzene attachment augments the distortion in DNA helical conformation. The distorted DNA retains nativelike pairing of bases at ambient temperatures, but shows weaker basepairing compared to native DNA at an elevated temperature. PMID- 25140429 TI - Insights into the structure and dynamics of measles virus nucleocapsids by 1H detected solid-state NMR. AB - (1)H-detected solid-state nuclear magnetic resonance (NMR) experiments are recorded on both intact and trypsin-cleaved sedimented measles virus (MeV) nucleocapsids under ultra-fast magic-angle spinning. High-resolution (1)H,(15)N fingerprints allow probing the degree of molecular order and flexibility of individual capsid proteins, providing an exciting atomic-scale complement to electro microscopy (EM) studies of the same systems. PMID- 25140430 TI - Complex pathways in folding of protein G explored by simulation and experiment. AB - The B1 domain of protein G has been a classic model system of folding for decades, the subject of numerous experimental and computational studies. Most of the experimental work has focused on whether the protein folds via an intermediate, but the evidence is mostly limited to relatively slow kinetic observations with a few structural probes. In this work we observe folding on the submillisecond timescale with microfluidic mixers using a variety of probes including tryptophan fluorescence, circular dichroism, and photochemical oxidation. We find that each probe yields different kinetics and compare these observations with a Markov State Model constructed from large-scale molecular dynamics simulations and find a complex network of states that yield different kinetics for different observables. We conclude that there are many folding pathways before the final folding step and that these paths do not have large free energy barriers. PMID- 25140431 TI - Characterization of protein flexibility using small-angle x-ray scattering and amplified collective motion simulations. AB - Large-scale flexibility within a multidomain protein often plays an important role in its biological function. Despite its inherent low resolution, small-angle x-ray scattering (SAXS) is well suited to investigate protein flexibility and determine, with the help of computational modeling, what kinds of protein conformations would coexist in solution. In this article, we develop a tool that combines SAXS data with a previously developed sampling technique called amplified collective motions (ACM) to elucidate structures of highly dynamic multidomain proteins in solution. We demonstrate the use of this tool in two proteins, bacteriophage T4 lysozyme and tandem WW domains of the formin-binding protein 21. The ACM simulations can sample the conformational space of proteins much more extensively than standard molecular dynamics (MD) simulations. Therefore, conformations generated by ACM are significantly better at reproducing the SAXS data than are those from MD simulations. PMID- 25140432 TI - Molecular basis of the mechanical hierarchy in myomesin dimers for sarcomere integrity. AB - Myomesin is one of the most important structural molecules constructing the M band in the force-generating unit of striated muscle, and a critical structural maintainer of the sarcomere. Using molecular dynamics simulations, we here dissect the mechanical properties of the structurally known building blocks of myomesin, namely alpha-helices, immunoglobulin (Ig) domains, and the dimer interface at myomesin's 13th Ig domain, covering the mechanically important C terminal part of the molecule. We find the interdomain alpha-helices to be stabilized by the hydrophobic interface formed between the N-terminal half of these helices and adjacent Ig domains, and, interestingly, to show a rapid unfolding and refolding equilibrium especially under low axial forces up to ~ 15 pN. These results support and yield atomic details for the notion of recent atomic-force microscopy experiments, namely, that the unique helices inserted between Ig domains in myomesin function as elastomers and force buffers. Our results also explain how the C-terminal dimer of two myomesin molecules is mechanically outperforming the helices and Ig domains in myomesin and elsewhere, explaining former experimental findings. This study provides a fresh view onto how myomesin integrates elastic helices, rigid immunoglobulin domains, and an extraordinarily resistant dimer into a molecular structure, to feature a mechanical hierarchy that represents a firm and yet extensible molecular anchor to guard the stability of the sarcomere. PMID- 25140433 TI - Dynamical phase transitions reveal amyloid-like states on protein folding landscapes. AB - Developing an understanding of protein misfolding processes presents a crucial challenge for unlocking the mysteries of human disease. In this article, we present our observations of beta-sheet-rich misfolded states on a number of protein dynamical landscapes investigated through molecular dynamics simulation and Markov state models. We employ a nonequilibrium statistical mechanical theory to identify the glassy states in a protein's dynamics, and we discuss the nonnative, beta-sheet-rich states that play a distinct role in the slowest dynamics within seven protein folding systems. We highlight the fundamental similarity between these states and the amyloid structures responsible for many neurodegenerative diseases, and we discuss potential consequences for mechanisms of protein aggregation and intermolecular amyloid formation. PMID- 25140434 TI - Functional dynamics of hexameric helicase probed by hydrogen exchange and simulation. AB - The biological function of large macromolecular assemblies depends on their structure and their dynamics over a broad range of timescales; for this reason, it is a significant challenge to investigate these assemblies using conventional experimental techniques. One of the most promising experimental techniques is hydrogen-deuterium exchange detected by mass spectrometry. Here, we describe to our knowledge a new computational method for quantitative interpretation of deuterium exchange kinetics and apply it to a hexameric viral helicase P4 that unwinds and translocates RNA into a virus capsid at the expense of ATP hydrolysis. Room-temperature dynamics probed by a hundred nanoseconds of all-atom molecular dynamics simulations is sufficient to predict the exchange kinetics of most sequence fragments and provide a residue-level interpretation of the low resolution experimental results. The strategy presented here is also a valuable tool to validate experimental data, e.g., assignments, and to probe mechanisms that cannot be observed by x-ray crystallography, or that occur over timescales longer than those that can be realistically simulated, such as the opening of the hexameric ring. PMID- 25140436 TI - Passive mechanical forces control cell-shape change during Drosophila ventral furrow formation. AB - During Drosophila gastrulation, the ventral mesodermal cells constrict their apices, undergo a series of coordinated cell-shape changes to form a ventral furrow (VF) and are subsequently internalized. Although it has been well documented that apical constriction is necessary for VF formation, the mechanism by which apical constriction transmits forces throughout the bulk tissue of the cell remains poorly understood. In this work, we develop a computational vertex model to investigate the role of the passive mechanical properties of the cellular blastoderm during gastrulation. We introduce to our knowledge novel data that confirm that the volume of apically constricting cells is conserved throughout the entire course of invagination. We show that maintenance of this constant volume is sufficient to generate invagination as a passive response to apical constriction when it is combined with region-specific elasticities in the membranes surrounding individual cells. We find that the specific sequence of cell-shape changes during VF formation is critically controlled by the stiffness of the lateral and basal membrane surfaces. In particular, our model demonstrates that a transition in basal rigidity is sufficient to drive VF formation along the same sequence of cell-shape change that we observed in the actual embryo, with no active force generation required other than apical constriction. PMID- 25140435 TI - Induction of peptide bond dipoles drives cooperative helix formation in the (AAQAA)3 peptide. AB - Cooperativity is a central feature in the formation of secondary structures in proteins. However, the driving forces behind this cooperativity are poorly understood. The present work shows that the cooperativity of helix formation in the acetyl-(AAQAA)3-NH2 peptide is significantly enhanced using an empirical force field that explicitly includes the treatment of electronic polarizability. Polarizable simulations yield helical content consistent with experimental measurements and indicate that the dependence of helical content on temperature is improved over additive models, though further sampling is required to fully validate this conclusion. Cooperativity is indicated by the peptide sampling either the coiled state or long helices with relatively low populations of short helices. The cooperativity is shown to be associated with enhanced dipole moments of the peptide backbone upon helix formation. These results indicate the polarizable force field to more accurately model peptide-folding cooperativity based on its physically realistic treatment of electronic polarizability. PMID- 25140437 TI - RNA-based regulation: dynamics and response to perturbations of competing RNAs. AB - The observation that, through a titration mechanism, microRNAs (miRNAs) can act as mediators of effective interactions among their common targets (competing endogenous RNAs or ceRNAs) has brought forward the idea (i.e., the ceRNA hypothesis) that RNAs can regulate each other in extended cross-talk networks. Such an ability might play a major role in posttranscriptional regulation to shape a cell's protein repertoire. Recent work focusing on the emergent properties of the cross-talk networks has emphasized the high flexibility and selectivity that may be achieved at stationarity. On the other hand, dynamical aspects, possibly crucial on the relevant timescales, are far less clear. We have carried out a dynamical study of the ceRNA hypothesis on a model of posttranscriptional regulation. Sensitivity analysis shows that ceRNA cross-talk is dynamically extended, i.e., it may take place on timescales shorter than those required to achieve stationarity even in cases where no cross-talk occurs in the steady state, and is possibly amplified. In addition, in the case of large, transfection-like perturbations, the system may develop a strongly nonlinear, threshold response. Finally, we show that the ceRNA effect provides a very efficient way for a cell to achieve fast positive shifts in the level of a ceRNA when necessary. These results indicate that competition for miRNAs may indeed provide an elementary mechanism to achieve system-level regulatory effects on the transcriptome over physiologically relevant timescales. PMID- 25140438 TI - The interrelations among stochastic pacing, stability, and memory in the heart. AB - Low pacing variability in the heart has been clinically reported as a risk factor for lethal cardiac arrhythmias and arrhythmic death. In ia previous simulation study, we demonstrated that stochastic pacing sustains an antiarrhythmic effect by moderating the slope of the action potential duration (APD) restitution curve, by reducing the propensity of APD alternans, converting discordant to concordant alternans, and ultimately preventing wavebreaks. However, the dynamic mechanisms relating pacing stochasticity to tissue stability are not yet known. In this work, we develop a mathematical framework to describe the APD signal using an autoregressive stochastic model, and we establish the interrelations between stochastic pacing, cardiac memory, and cardiac stability, as manifested by the degree of APD alternans. Employing stability analysis tools, we show that increased stochasticity in the ventricular tissue activation sequence works to lower the maximal absolute eigenvalues of the stochastic model, thereby contributing to increased stability. We also show that the memory coefficients of the autoregressive model are modulated by pacing stochasticity in a nonlinear, biphasic way, so that for exceedingly high levels of pacing stochasticity, the antiarrhythmic effect is hampered by increasing APD variance. This work may contribute to establishment of an optimal antiarrhythmic pacing protocol in a future study. PMID- 25140439 TI - Evaluating complex interventions: perspectives and issues for health behaviour change interventions. AB - OBJECTIVE: Health behaviour change interventions (HBCIs), used in health education, health promotion, patient education and psychotherapy areas, are considered complex interventions. The objective of this article is to discuss the value and limitations of using randomised clinical trials (RCTs) to asses HBCIs. METHODS: A scoping review of the literature was conducted to identify the main challenges of using RCTs for evaluating HBCIs. The issues were illustrated by case studies selected from research conducted by our multidisciplinary team. RESULTS: In complex interventions, effects are produced not only by the intervention, but are strongly linked to context. Issues relating to transferability of results are therefore critical, and require adjustments to the RCT model. Sampling bias, biases related to the experimental conditions and biases due to the absence of double-blindness were examined and illustrated by case studies. CONCLUSION: The results underline the importance of a multidisciplinary approach. They call for adapted or alternative evaluation models that overcome the limitations of RCTs. PMID- 25140440 TI - Lattice model for silica polymerization: Monte Carlo simulations of the transition between gel and nanoparticle phases. AB - We present Monte Carlo simulations of a lattice model describing silica polymerization with an emphasis on the transition between gel states and nanoparticle states as the pH and silica concentration are varied. The pH in the system is controlled by the addition of a structure-directing agent (SDA) of the type SDA(+)(OH(-)). The silica units are represented by corner-sharing tetrahedra on a body-centered cubic lattice and the SDA(+) species by single sites with near neighbor repulsions. We focus on two systems: one with a low silica concentration with composition comparable to that of the clear solution silicalite-1 zeolite synthesis and a high silica concentration system that leads to gel states. In the dilute system, clusters have a core-shell structure, with the core predominantly comprised of silica with some SDA(+) cations, surrounded by a shell of only SDA(+) cations. Moreover, the average cluster size gradually decreases from 2 to 1.6 nm with increasing pH. The concentrated system forms a gel that remains stable to increasing pH up to about 9.2. At pH values in the range of 9.2-10, the gel transforms to nanoparticles of size around 1.0 nm, surprisingly smaller than those in the dilute system. We also study the evolution of the Q(n) distribution (a measure of the silica network structure) for both systems and obtain good agreement with (29)Si NMR data available for the concentrated system. PMID- 25140441 TI - Guillain-Barre syndrome associated with Japanese encephalitis virus infection in China. AB - Abstract Guillain-Barre syndrome (GBS) is preceded by an infection in about two thirds of patients. However, the infectious organism is often not identified. GBS secondary to Japanese encephalitis virus (JEV) infection has been reported only in India. Herein, we report a case of GBS preceded by JEV infection in China. A 23-year-old male had generalized weakness, numbness in the extremities, and bilateral facial nerve paralysis. One week prior, he had a high fever with headache, and several days later, he developed facial diplegia and sensory disturbances. Physical examination revealed facial diplegia and a weak gag reflex, quadriparesis more pronounced distally, generalized hyporeflexia, and no Babinski sign. JEV IgM and hepatitis B surface antibody (HbsAb) tests were positive. Other tests for hepatitis B infection were negative. Nerve electrophysiology suggested an acute demyelinating sensorimotor polyradiculoneuropathy. His cerebrospinal fluid was clear, the leukocyte count was 5 * 10(6)/L (normal range: 0-5 * 10(6)/L), protein 0.62 g/L (normal range: 0.15-0.45 g/L), and JEV IgM was weakly positive. He was diagnosed with GBS associated with a recent JEV infection. Intravenous (IV) immunoglobulins combined with IV methylprednisone was administered for 5 days, and at the 3-month follow up, a complete neurological recovery was noted. GBS may be associated with JEV infection. GBS exhibits a good response to intravenous immunoglobulin or plasma exchange and has a good prognosis making prompt diagnosis important. PMID- 25140442 TI - Structural study of the apatite Nd8Sr2Si6O26 by Laue neutron diffraction and single-crystal Raman spectroscopy. AB - A single-crystal structure determination of Nd8Sr2Si6O26 apatite, a prototype intermediate-temperature electrolyte for solid oxide fuel cells grown by the floating-zone method, was completed using the combination of Laue neutron diffraction and Raman spectroscopy. While neutron diffraction was in good agreement with P63/m symmetry, the possibility of P63 could not be convincingly excluded. This ambiguity was removed by the collection of orientation-dependent Raman spectra that could only be consistent with P63/m. The composition of Nd8Sr2Si6O26 was independently verified by powder X-ray diffraction in combination with electron probe microanalysis, with the latter confirming a homogeneous distribution of Sr and the absence of chemical zonation commonly observed in apatites. This comprehensive crystallochemical description of Nd8Sr2Si6O26 provides a baseline to quantify the efficacy of cation vacancies, oxygen superstoichiometry, and symmetry modification for promoting oxygen-ion mobility. PMID- 25140443 TI - DddD is a CoA-transferase/lyase producing dimethyl sulfide in the marine environment. AB - Dimethyl sulfide (DMS) is produced in oceans in vast amounts (>10(7) tons/year) and mediates a wide range of processes from regulating marine life forms to cloud formation. Nonetheless, none of the enzymes that produce DMS from dimethylsulfoniopropionate (DMSP) has been adequately characterized. We describe the expression and purification of DddD from the marine bacterium Marinomonas sp. MWYL1 and its biochemical characterization. We identified DMSP and acetyl coenzyme A to be DddD's native substrates and Asp602 as the active site residue mediating the CoA-transferase prior to lyase activity. These findings shed light on the biochemical utilization of DMSP in the marine environment. PMID- 25140444 TI - The use of a mobile assistant learning system for health education based on project-based learning. AB - With the development of mobile devices and wireless technology, mobile technology has gradually infiltrated nursing practice courses to facilitate instruction. Mobile devices save manpower and reduce errors while enhancing nursing students' professional knowledge and skills. To achieve teaching objectives and address the drawbacks of traditional education, this study presents a mobile assistant learning system to help nursing students prepare health education materials. The proposed system is based on a project-based learning strategy to assist nursing students with internalizing professional knowledge and developing critical thinking skills. Experimental results show that the proposed mobile system and project-based learning strategy can promote learning effectiveness and efficiency. Most nursing students and nursing educators showed positive attitudes toward this mobile learning system and looked forward to using it again in related courses in the future. PMID- 25140445 TI - Creation of a virtual triage exercise: an interprofessional communication strategy. AB - Virtual reality simulation as a teaching method is gaining increased acceptance and presence in institutions of higher learning. This study presents an innovative strategy using the interdisciplinary development of a nonimmersive virtual reality simulation to facilitate interprofessional communication. The purpose of this pilot project was to describe nursing students' attitudes related to interprofessional communication following the collaborative development of a disaster triage virtual reality simulation. Collaboration between and among professionals is integral in enhancing patient outcomes. In addition, ineffective communication is linked to detrimental patient outcomes, especially during times of high stress. Poor communication has been identified as the root cause of the majority of negative sentinel events occurring in hospitals. The simulation development teaching model proved useful in fostering interprofessional communication and mastering course content. Mean scores on the KidSIM Attitudes Towards Teamwork in Training Undergoing Designed Educational Simulation survey demonstrated that nursing students, after simulation experience,had agreement to strong agreement inall areas surveyed including interprofessional education, communication, roles and responsibilities of team members, and situational awareness. The findings indicate that students value interprofessional teamwork and the opportunity to work with other disciplines. PMID- 25140446 TI - Cucurbitane glycosides derived from mogroside IIE: structure-taste relationships, antioxidant activity, and acute toxicity. AB - Mogroside IIE is a bitter triterpenoid saponin which is the main component of unripe Luo Han Guo fruit and a precursor of the commercially available sweetener mogroside V. In this study, we developed an enzymatic glycosyl transfer method, by which bitter mogroside IIE could be converted into a sweet triterpenoid saponin mixture. The reactant concentration, temperature, pH and buffer system were studied. New saponins with the alpha-glucose group were isolated from the resulting mixtures, and the structures of three components of the extract were determined. The structure-taste relationships of these derivatives were also studied together with those of the natural mogrosides. The number and stereoconfiguration of glucose groups present in the mogroside molecules were found to be the main factor to determine the sweet or bitter taste of a compound. The antioxidant and food safety properties were initially evaluated by their radical scavenging ability and via 7 day mice survival tests, respectively. The results showed that the sweet triterpenoid saponin mixture has the same favorable physiological and safety characteristics as the natural mogrosides. PMID- 25140447 TI - Oligo-carrageenan kappa-induced reducing redox status and activation of TRR/TRX system increase the level of indole-3-acetic acid, gibberellin A3 and trans zeatin in Eucalyptus globulus trees. AB - Eucalyptus globulus trees treated with oligo-carrageenan (OC) kappa showed an increase in NADPH, ascorbate and glutathione levels and activation of the thioredoxin reductase (TRR)/thioredoxin (TRX) system which enhance photosynthesis, basal metabolism and growth. In order to analyze whether the reducing redox status and the activation of thioredoxin reductase (TRR)/thioredoxin (TRX) increased the level of growth-promoting hormones, trees were treated with water (control), with OC kappa, or with inhibitors of ascorbate synthesis, lycorine, glutathione synthesis, buthionine sulfoximine (BSO), NADPH synthesis, CHS-828, and thioredoxin reductase activity, auranofine, and with OC kappa, and cultivated for four additional months. Eucalyptus trees treated with OC kappa showed an increase in the levels of the auxin indole 3-acetic acid (IAA), gibberellin A3 (GA3) and the cytokinin trans-zeatin (t-Z) as well as a decrease in the level of the brassinosteroid epi-brassinolide (EB). In addition, treatment with lycorine, BSO, CHS-828 and auranofine inhibited the increase in IAA, GA3 and t-Z as well as the decrease in EB levels. Thus, the reducing redox status and the activation of TRR/TRX system induced by OC kappa increased the levels of IAA, GA3 and t-Z levels determining, at least in part, the stimulation of growth in Eucalyptus trees. PMID- 25140448 TI - Identification of two novel alpha1-AR agonists using a high-throughput screening model. AB - alpha1-Adrenoceptors (ARs; 1A, 1B, and 1D) have been determined to perform different prominent functions in the physiological responses of the sympathetic nervous system. A high-throughput screening assay (HTS) was set up to detect alpha1-AR subtype-selective agonists by a dual-luciferase reporter assay in HEK293 cells. Using the HTS assay, two novel compounds, CHE3 and CHK3, were discovered as alpha1-ARs agonists in alpha1-ARs expressed in HEK293 cells. These compounds also showed moderate/weak anti-proliferative activities against tested cancer cell lines. The HTS assay proposed in this study represents a potential method for discovering more alpha1-AR subtype-selective ligands. PMID- 25140449 TI - Magnetite nanostructures as novel strategies for anti-infectious therapy. AB - This review highlights the current situation of antimicrobial resistance and the use of magnetic nanoparticles (MNPs) in developing novel routes for fighting infectious diseases. The most important two directions developed recently are: (i) improved delivery of antimicrobial compounds based on a drastic decrease of the minimal inhibition concentration (MIC) of the drug used independently; and (ii) inhibition of microbial attachment and biofilm development on coated medical surfaces. These new directions represent promising alternatives in the development of new strategies to eradicate and prevent microbial infections that involve resistant and biofilm-embedded bacteria. Recent promising applications of MNPs, as the development of delivery nanocarriers and improved nanovehicles for the therapy of different diseases are discussed, together with the mechanisms of microbial inhibition. PMID- 25140450 TI - Effect of redox modulating NRF2 activators on chronic kidney disease. AB - Chronic kidney disease (CKD) is featured by a progressive decline of kidney function and is mainly caused by chronic diseases such as diabetes mellitus and hypertension. CKD is a complex disease due to cardiovascular complications and high morbidity; however, there is no single treatment to improve kidney function in CKD patients. Since biological markers representing oxidative stress are significantly elevated in CKD patients, oxidative stress is receiving attention as a contributing factor to CKD pathology. Nuclear factor erythroid-2 related factor 2 (NRF2) is a predominant transcription factor that regulates the expression of a wide array of genes encoding antioxidant proteins, thiol molecules and their generating enzymes, detoxifying enzymes, and stress response proteins, all of which can counteract inflammatory and oxidative damages. There is considerable experimental evidence suggesting that NRF2 signaling plays a protective role in renal injuries that are caused by various pathologic conditions. In addition, impaired NRF2 activity and consequent target gene repression have been observed in CKD animals. Therefore, a pharmacological intervention activating NRF2 signaling can be beneficial in protecting against kidney dysfunction in CKD. This review article provides an overview of the role of NRF2 in experimental CKD models and describes current findings on the renoprotective effects of naturally occurring NRF2 activators, including sulforaphane, resveratrol, curcumin, and cinnamic aldehyde. These experimental results, coupled with recent clinical experiences with a synthetic triterpenoid, bardoxolone methyl, have brought a light of hope for ameliorating CKD progression by preventing oxidative stress and maintaining cellular redox homeostasis. PMID- 25140451 TI - Effects of drying methods on physicochemical and immunomodulatory properties of polysaccharide-protein complexes from litchi pulp. AB - Dried litchi pulp has been used in traditional remedies in China for many years to treat various diseases, and the therapeutic activity has been, at least partly, attributed to the presence of bioactive polysaccharides. Polysaccharide protein complexes from vacuum freeze-(VF), vacuum microwave-(VM) and heat pump (HP) dried litchi pulp, which were coded as LP-VF, LP-VM and LP-HP, were comparatively studied on the physicochemical and immunomodulatory properties. LP HP had a predominance of galactose, while glucose was the major sugar component in LP-VF and LP-VM. Compared with LP-VF and LP-VM, LP-HP contained more aspartate and glutamic in binding protein. LP-HP also exhibited a stronger stimulatory effect on splenocyte proliferation at 200 MUg/mL and triggered higher NO, TNF alpha and IL-6 secretion from RAW264.7 macrophages. Different drying methods caused the difference in physicochemical properties of polysaccharide-protein complexes from dried litchi pulp, which resulted in significantly different immunomodulatory activity. HP drying appears to be the best method for preparing litchi pulp to improve its immunomodulatory properties. PMID- 25140455 TI - Development and characterization of a resistance spot welding aerosol generator and inhalation exposure system. AB - Limited information exists regarding the health risks associated with inhaling aerosols that are generated during resistance spot welding of metals treated with adhesives. Toxicology studies evaluating spot welding aerosols are non-existent. A resistance spot welding aerosol generator and inhalation exposure system was developed. The system was designed by directing strips of sheet metal that were treated with an adhesive to two electrodes of a spot welder. Spot welds were made at a specified distance from each other by a computer-controlled welding gun in a fume collection chamber. Different target aerosol concentrations were maintained within the exposure chamber during a 4-h exposure period. In addition, the exposure system was run in two modes, spark and no spark, which resulted in different chemical profiles and particle size distributions. Complex aerosols were produced that contained both metal particulates and volatile organic compounds (VOCs). Size distribution of the particles was multi-modal. The majority of particles were chain-like agglomerates of ultrafine primary particles. The submicron mode of agglomerated particles accounted for the largest portion of particles in terms of particle number. Metal expulsion during spot welding caused the formation of larger, more spherical particles (spatter). These spatter particles appeared in the micron size mode and accounted for the greatest amount of particles in terms of mass. With this system, it is possible to examine potential mechanisms by which spot welding aerosols can affect health, as well as assess which component of the aerosol may be responsible for adverse health outcomes. PMID- 25140454 TI - Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats. AB - Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (R(L)) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline R(L) was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased R(L) and result in endothelial dysfunction, but otherwise had minor effects on the lung. PMID- 25140456 TI - Sodium/Lithium storage behavior of antimony hollow nanospheres for rechargeable batteries. AB - Sodium-ion batteries (SIBs) have come up as an alternative to lithium-ion batteries (LIBs) for large-scale applications because of abundant Na storage in the earth's crust. Antimony (Sb) hollow nanospheres (HNSs) obtained by galvanic replacement were first applied as anode materials for sodium-ion batteries and exhibited superior electrochemical performances with high reversible capacity of 622.2 mAh g(-1) at a current density of 50 mA g(-1) after 50 cycles, close to the theoretical capacity (660 mAh g(-1)); even at high current density of 1600 mA g( 1), the reversible capacities can also reach 315 mAh g(-1). The benefits of this unique structure can also be extended to LIBs, resulting in reversible capacity of 627.3 mAh g(-1) at a current density of 100 mAh g(-1) after 50 cycles, and at high current density of 1600 mA g(-1), the reversible capacity is 435.6 mAhg(-1). Thus, these benefits from the Sb HNSs are able to provide a robust architecture for SIBs and LIBs anodes. PMID- 25140457 TI - Antiparasitic efficacy of Gracillin and Zingibernsis newsaponin from Costus speciosus (Koen ex. Retz) Sm. against Ichthyophthirius multifiliis. AB - The present study aims to evaluate the antiparasitic activity of active components from Costus speciosus against Ichthyophthirius multifiliis. Bioassay guided fractionation was employed to identify active compounds from C. speciosus yielding 2 bioactive compounds: Gracillin and Zingibernsis newsaponin. In-vitro assays revealed that Gracillin and Zingibernsis newsaponin could be 100% effective against I. multifiliis at concentrations of 0.8 and 4.5 mg L(-1), with median effective concentration (EC50) values of 0.53 and 3.2 mg L(-1), respectively. All protomonts and encysted tomonts were killed when the concentrations of Gracillin and Zingibernsis newsaponin were 1.0 and 5.0 mg L( 1). In-vivo experiments demonstrated that fish treated with Gracillin and Zingibernsis newsaponin at concentrations of 1.0 and 5.0 mg L(-1) carried significantly fewer parasites than the control (P<0.05). Mortality of fish did not occur in the treatment group (Zingibernsis newsaponin at 5.0 mg L(-1)) during the trial, although 100% of untreated fish died. Acute toxicities (LD50) of Gracillin and Zingibernsis newsaponin for grass carp were 1.64 and 20.7 mg L(-1), respectively. These results provided evidence that the 2 compounds can be selected as lead compounds for the development of new drugs against I. multifiliis. PMID- 25140459 TI - Synthesis and structures of mononuclear 3,4-bis(trifluoromethyl)pyrrolyl complexes of Rh(I) and Ni(II). AB - New mononuclear complexes of the 3,4-bis(trifluoromethyl)pyrrolyl ligand (3,4 (CF3)2-Pyr(-)) with Rh(I) and Ni(II) are reported. Reaction of 3,4-(CF3)2-PyrNa with [Rh(COD)Cl]2 produces [Rh(PMe3)3(3,4-(CF3)2-Pyr)] (1) while reaction of 3,4 (CF3)2-PyrH with [Ni(PMe3)2Me2] (2) or [Ni(PMe3)2Ph2] (4) gives [trans Ni(PMe3)2(3,4-(CF3)2-Pyr)(CH3)] (3) or [trans-Ni(PMe3)2(C6H5)(3,4-(CF3)2-Pyr)] (5) respectively. Complexes 1, 3 and 5 have been characterized spectroscopically and all five compounds have been structurally characterized by single crystal X ray diffraction studies. PMID- 25140460 TI - Horizontal right axillary minithoracotomy: aesthetic and effective option for atrial and ventricular septal defect repair in infants and toddlers. AB - INTRODUCTION: Congenital heart defects treatment shows progressive reduction in morbidity and mortality, however, the scar, resulting from ventricular (VSD) and atrial septal defect (ASD) repair, may cause discomfort. Right axillary minithoracotomy approach, by avoiding the breast growth region, is an option for correction of these defects that may provide better aesthetic results at low cost. Since October 2011, we have been using this technique for repairing VSD and ASD defects as well as associated defects. OBJECTIVES: To evaluate the efficacy of this method in children undergoing correction of VSD and ASD, to compare perioperative clinical outcomes with those repaired by median sternotomy, and to evaluate the aesthetic result. METHODS: Perioperative clinical data of 25 patients submitted to axillary thoracotomy were compared with data from a paired group of 25 patients with similar heart defects repaired by median sternotomy, from October 2011 to August 2012. RESULTS: Axillary approach was possible even in infants. There was no mortality and the main perioperative variables were similar in both groups, except for lower use of blood products in the axillary group (6/25) vs. control (13/25), with statistical difference (P =0.04). The VSD size varied from 7 to 15 mm in axillary group. Cannulation of the aorta and vena cavae was performed through the main incision, whose size ranged from 3 to 5 cm in the axillary group, with excellent aesthetic results. CONCLUSION: The axillary thoracotomy was effective, allowing for a heart defect repair similar to the median sternotomy, with more satisfactory aesthetic results and reduced blood transfusion, and it can be safely used in infants. PMID- 25140461 TI - Impact of type of procedure and surgeon on EuroSCORE operative risk validation. AB - OBJECTIVE: EuroSCORE has been used in cardiac surgery operative risk assessment, despite important variables were not included. The objective of this study was to validate EuroSCORE on mortality prediction in a Brazilian cardiovascular surgery center, defining the influence of type of procedure and surgical team. METHODS: Between January 2006 and June 2011, 2320 consecutive adult patients were studied. According to additive EuroSCORE, patients were divided into low risk (score<2), medium risk (3 - 5), high risk (6 - 11) and very high risk (>12). The relation between observed mortality (O) and expected mortality (E) according to logistic EuroSCORE was calculated for each of the groups, types of procedures and surgeons with > 150 operations, and analyzed by logistic regression. RESULTS: EuroSCORE correlated to the observed mortality (O/E=0.94; P<0.0001; area under the curve 0.78). However, it overestimated the mortality in very high risk patients (O/E=0.74; P=0.001). EuroSCORE tended to overestimate isolated myocardial revascularization mortality (O/E=0.81; P=0.0001) and valve surgery mortality (O/E=0.89; P=0.007) and it tended to underestimate combined procedures mortality (O/E=1.09; P<0.0001). EuroSCORE overestimated surgeon A mortality (O/E=0.46; P<0.0001) and underestimated surgeon B mortality (O/E=1.3; P<0.0001), in every risk category. CONCLUSION: In the present population, EuroSCORE overestimates mortality in very high risk patients, being influenced by type of procedure and surgical team. The most appropriate surgical team may minimize risks imposed by preoperative profiles. PMID- 25140462 TI - Predictors of stroke in patients undergoing cardiac surgery. AB - OBJECTIVE: To determine the risk factors related to the development of stroke in patients undergoing cardiac surgery. METHODS: A historical cohort study. We included 4626 patients aged > 18 years who underwent coronary artery bypass surgery, heart valve replacement surgery alone or heart valve surgery combined with coronary artery bypass grafting between January 1996 and December 2011. The relationship between risk predictors and stroke was assessed by logistic regression model with a significance level of 0.05. RESULTS: The incidence of stroke was 3% in the overall sample. After logistic regression, the following risk predictors for stroke were found: age 50-65 years (OR=2.11 - 95% CI 1.05 4.23 - P=0.036) and age >66 years (OR=3.22 - 95% CI 1.6-6.47 - P=0.001), urgent and emergency surgery (OR=2.03 - 95% CI 1.20-3.45 - P=0.008), aortic valve disease (OR=2.32 - 95% CI 1.18-4.56 - P=0.014), history of atrial fibrillation (OR=1.88 - 95% CI 1.05-3.34 - P=0.032), peripheral artery disease (OR=1.81 - 95% CI 1.13-2.92 - P=0.014), history of cerebrovascular disease (OR=3.42 - 95% CI 2.19-5.35 - P<0.001) and cardiopulmonary bypass time > 110 minutes (OR=1.71 - 95% CI 1.16-2.53 - P=0.007). Mortality was 31.9% in the stroke group and 8.5% in the control group (OR=5.06 - 95% CI 3.5-7.33 - P<0.001). CONCLUSION: The study identified the following risk predictors for stroke after cardiac surgery: age, urgent and emergency surgery, aortic valve disease, history of atrial fibrillation, peripheral artery disease, history of cerebrovascular disease and cardiopulmonary bypass time > 110 minutes. PMID- 25140464 TI - Comparison of fractal dimension and Shannon entropy in myocytes from rats treated with histidine-tryptophan-glutamate and histidine-tryptophan cetoglutarate. AB - INTRODUCTION: Solutions that cause elective cardiac arrest are constantly evolving, but the ideal compound has not yet been found. The authors compare a new cardioplegic solution with histidine-tryptophan-glutamate (Group 2) and other one with histidine-tryptophan-cetoglutarate (Group 1) in a model of isolated rat heart. OBJECTIVE: To quantify the fractal dimension and Shannon entropy in rat myocytes subjected to cardioplegia solution using histidine-tryptophan with glutamate in an experimental model, considering the caspase markers, IL-8 and KI 67. METHODS: Twenty male Wistar rats were anesthetized and heparinized. The chest was opened, the heart was withdrawn and 40 ml/kg of cardioplegia (with histidine tryptophan-cetoglutarate or histidine-tryptophan-glutamate solution) was infused. The hearts were kept for 2 hours at 4oC in the same solution, and thereafter placed in the Langendorff apparatus for 30 min with Ringer-Locke solution. Analyzes were performed for immunohistochemical caspase, IL-8 and KI-67. RESULTS: The fractal dimension and Shannon entropy were not different between groups histidine-tryptophan-glutamate and histidine-tryptophan-acetoglutarate. CONCLUSION: The amount of information measured by Shannon entropy and the distribution thereof (given by fractal dimension) of the slices treated with histidine-tryptophan-cetoglutarate and histidine-tryptophan-glutamate were not different, showing that the histidine-tryptophan-glutamate solution is as good as histidine-tryptophan-acetoglutarate to preserve myocytes in isolated rat heart. PMID- 25140465 TI - Pain and cardiorespiratory responses of children during physiotherapy after heart surgery. AB - OBJECTIVE: The aim of the present study was to determine the occurrence of pain and changes in blood pressure, heart rate, respiratory rate, and arterial oxygen saturation associated with physiotherapy in children undergoing cardiac surgery. METHODS: Eighteen extubated children were assessed for the presence of pain using the face, legs, activity, cry, consolability scale, and blood pressure, heart rate, respiratory rate and arterial oxygen saturation were simultaneously recorded. The physiological parameters were measured at the following time periods: immediately before physiotherapy, five and 10 minutes after the beginning of physiotherapy, and five minutes after its end. Pain was assessed immediately before physiotherapy, ten minutes after the beginning of physiotherapy and five minutes after its end. Pain and physiological changes were assessed by the Friedman test and the correlation between the physiological parameters and the pain scores was assessed by the Spearman test. RESULTS: Pain increased during physiotherapy and decreased significantly after it compared to pre-physiotherapy scores. Systolic blood pressure and heart rate increased significantly after 10 minutes of the beginning of physiotherapy. Arterial oxygen saturation tended to decrease during physiotherapy and to increase after it, although without significance. The correlation between pain scores and the physiological variables was significant only for systolic blood pressure and heart rate ten minutes after the beginning of physiotherapy. CONCLUSION: Manipulation after the beginning of physiotherapy seems to be accompanied by significant pain and by important associated cardiovascular changes. Apparent analgesia and improved respiratory function were observed after respiratory physiotherapy. PMID- 25140463 TI - Analysis of transit time flow of the right internal thoracic artery anastomosed to the left anterior descending artery compared to the left internal thoracic artery. AB - INTRODUCTION: We evaluated with transit time flow the performance of the right and left thoracic arteries when used as a graft for the left anterior descending artery. METHODS: Fifty patients undergoing surgery for myocardial revascularization without cardiopulmonary bypass were divided into two groups. In group A patients received graft of right internal mammary artery to the anterior interventricular branch. In group B patients received graft of left internal mammary artery to the same branch. At the end of the operation the flow was assessed by measuring transit time. RESULTS: In group A, mean age was 60.6 +/- 9.49 years. The average height and weight of the group was 80.4 +/- 10.32 kg and 169.2 +/- 6.86 cm. The average number of grafts per patient in this group was 3.28 +/- 1.49. The mean flow and distal resistance obtained in right internal thoracic artery was 42.1 +/- 23.4 ml/min and 2.8 +/- 0.9 respectively. In group B, the mean age was 59.8 +/- 9.7 years. The average height and weight of this group was 77.7 +/- 14.22 kg and 166.0 +/- 8.2 cm. The average number of grafts per patient in this group was 3.08 +/- 0.82. The mean flow and distal resistance observed in this group was 34.2 +/- 19.1 ml/min and 2.0 +/- 0.7. There were no deaths in this series. CONCLUSION: Right internal mammary artery presented a similar behavior to left internal mammary artery when anastomosed to the anterior interventricular branch of the left coronary artery. There was no statistical difference between the measured flow obtained between both arteries. PMID- 25140466 TI - Impact of hospital infections on patients outcomes undergoing cardiac surgery at Santa Casa de Misericordia de Marilia. AB - OBJECTIVE: This study aimed to determine the incidence of nosocomial infections, the risk factors and the impact of these infections on mortality among patients undergoing to cardiac surgery. METHODS: Retrospective cohort study of 2060 consecutive patients from 2006 to 2012 at the Santa Casa de Misericordia de Marilia. RESULTS: 351 nosocomial infections were diagnosed (17%), 227 non surgical infections and 124 surgical wound infections. Major infections were mediastinitis (2.0%), urinary tract infection (2.8%), pneumonia (2.3%), and bloodstream infection (1.7%). The in-hospital mortality was 6.4%. Independent variables associated with non-surgical infections were age > 60 years (OR 1.59, 95% CI 1.09 to 2.31), ICU stay > 2 days (OR 5, 49, 95% CI 2.98 to 10, 09), mechanical ventilation > 2 days (OR11, 93, 95% CI 6.1 to 23.08), use of urinary catheter > 3 days (OR 4.85 95% CI 2.95 -7.99). Non-surgical nosocomial infections were more frequent in patients with surgical wound infection (32.3% versus 7.2%, OR 6.1, 95% CI 4.03 to 9.24). Independent variables associated with mortality were age greater than 60 years (OR 2.0; 95% CI 1.4 t o3.0), use of vasoactive drugs (OR 3.4, 95% CI 1.9 to 6, 0), insulin use (OR 1.8; 95% CI 1.2 to 2.8), surgical reintervention (OR 4.4; 95% CI 2.1 to 9.0) pneumonia (OR 4.3; 95% CI 2.1 to 8.9) and bloodstream infection (OR = 4.7, 95% CI 2.0 to 11.2). CONCLUSION: Non surgical hospital infections are common in patients undergoing cardiac surgery; they increase the chance of surgical wound infection and mortality. PMID- 25140468 TI - High postoperative serum levels of surfactant type B as novel prognostic markers for congenital heart surgery. AB - OBJECTIVE: Congenital heart diseases are observed in 5 to 8 of every 1000 live births. The presence of a valuable biomarker during the surgical periods may aid the clinician in a more accurate prognosis during treatment. METHODS: For this reason, surfactant protein B plasma levels may help to evaluate patients with cardiac problems diminishing the alveolocapillary membrane stability. In this study, plasma levels of this biomarker were measured in the preoperative and postoperative periods. This study was conducted to detect the differences between pulmonary hypertensive and normotensive patients. The differences before and after cardiopulmonary bypass were examined. RESULTS: The differences in cardiopulmonary bypass time, cross-clamp time , inotropic support dose, and duration of intensive care of patients with and without pulmonary hypertensive were found to be statistically significant (P<0.05). The results revealed that this pathophysiological state was related to other variables that were studied. We believe that the differences in preoperative and postoperative SPB levels could be attributed to alveolocapillary membrane damage and alveolar surfactant dysfunction. We found that this pathophysiological condition was significantly associated with postoperative parameters. CONCLUSION: The findings of the current study showed that surfactant protein B was present in the blood of patients with a congenital heart disease during the preoperative period. Long by-pass times may exert damage to the alveolocapillary membrane in patients with pulmonary hypertension and preoperative heart failure, and it is recommended to keep the option of surfactant therapy in mind during the postoperative course at the intensive care unit before preparing the patients for extubation. PMID- 25140467 TI - Management of multivessel coronary disease after primary angioplasty: staged reintervention versus optimized clinical treatment and two-year follow-up. AB - OBJECTIVE: In the clinical scenario of ST-segment elevation acute myocardial infarction, several patients with multivessel coronary atherosclerotic disease are discharged without a defined strategy to monitor the residual atherosclerotic lesions. The clinical endpoints evaluated were cardiovascular death, symptoms of angina pectoris, rehospitalization for a new acute coronary syndrome, and the necessity of reintervention during the two-year follow-up. METHODS: This observational, prospective, and historical study included multivessel coronary atherosclerotic disease patients who were admitted to a tertiary care university hospital with ST-segment elevation acute myocardial infarction and underwent primary percutaneous coronary intervention with stent implantation only at the culprit lesion site; these patients were monitored in the outpatient clinic according to two treatments: the Clinical Group - CG (optimized pharmacological therapy associated with counseling for a healthy diet and cardiac rehabilitation) or the Intervention Group - IG (new staged percutaneous coronary intervention or surgical coronary artery bypass graft surgery combined with the previously prescribed treatment). RESULTS: Of 143 patients consecutively admitted with ST segment elevation acute myocardial infarction, 57 were eligible for the study (CG=44 and IG=13). Regarding the clinical endpoints, the cardiovascular death rate did not differ between the CG and IG. The symptom of angina pectoris and the rehospitalization rate for a new episode of acute coronary syndrome were accentuated in the CG (P=0.020 and P=0.049, respectively) mainly in individuals with evidence of ischemia evidenced by myocardial scintigraphy (P<0.001 and P=0.001, respectively) which culminated in an even greater need for reintervention (P=0.001) in this subgroup of patients. CONCLUSION: The staged intervention was demonstrated to be safe and able to reduce angina pectoris and rehospitalization for a new episode of acute coronary syndrome. In addition, it decreases the likelihood of unplanned reinterventions of patients without ischemia evidenced by myocardial scintigraphy. PMID- 25140469 TI - Comparative analysis of the patency of the internal thoracic artery in the CABG of left anterior descending artery: 6-month postoperative coronary CT angiography evaluation. AB - OBJECTIVE: To assess the patency of the pedicled right internal thoracic artery with an anteroaortic course and compare it to the patency of the left internal thoracic artery , in anastomosis to the left anterior descending artery in coronary artery bypass grafting by using coronary CT angiography at 6 months postoperatively. METHODS: Between December 2008 and December 2011, 100 patients were selected to undergo a prospective coronary artery bypass grafting procedure without cardiopulmonary bypass. The patients were randomly divided by a computer generated list into Group-1 (G-1) and Group-2 (G-2), comprising 50 patients each, the technique used was known at the beginning of the surgery. In G-1, coronary artery bypass grafting was performed using the left internal thoracic artery for the left anterior descending and the free right internal thoracic artery for the circumflex, and in G-2, coronary artery bypass grafting was performed using the right internal thoracic artery pedicled to the left anterior descending and the left internal thoracic artery pedicled to the circumflex territory. RESULTS: The groups were similar with regard to the preoperative clinical data. A male predominance of 75.6% and 88% was observed in G-1 and G-2, respectively. Five patients migrated from G-1 to G-2 because of atheromatous disease in the ascending aorta. The average number of distal anastomoses was 3.48 (SD=0.72) in G 1 and 3.20 (SD=0.76) in G-2. Coronary CT angiography in 96 re-evaluated patients showed that all ITAs, right or left, used in situ for the left anterior descending were patent. There were no deaths in either group. CONCLUSION: Coronary artery bypass grafting surgery involving anastomosis of the anteroaortic right internal thoracic artery to the left anterior descending artery has an outcome similar to that obtained using the left internal thoracic artery for the same coronary site. PMID- 25140471 TI - Morphologic expression of the left coronary artery in pigs. An approach in relation to human heart. AB - INTRODUCTION: In spite of its importance as an experimental model, the information on the left coronary artery in pigs is sparse. OBJECTIVE: To determine the morphologic features of the left coronary artery in pigs. METHODS: We evaluated 158 pig hearts. The left coronary artery was perfused with synthetic resin after their ostia had been catheterized. Diameters and courses of the vascular beds were measured with an electronic caliper (Mitutoyo(r)). RESULTS: The diameter of left coronary artery was 6.98 +/- 1.56 mm and its length was 3.51 +/- 0.99 mm. It was found to end up by bifurcating itself into the anterior interventricular artery and the circumflex artery in 79% of the cases, and by trifurcating in 21% of the cases, with the presence of the diagonal artery. The anterior interventricular artery ended up at the apex in 79.7% of the cases, and the circumflex artery at the posterior aspect of the left ventricle in 64% of the case, this artery never reached the posterior interventricular sulcus. An anastomosis between the terminal branches of the anterior interventricular artery and the posterior interventricular artery was found in 7.6% of the specimens. The antero-superior branch of the anterior interventricular artery occurred in 89.9% of the hearts. A left marginal branch was observed in 87.9% of the cases with a diameter of 2.25 +/- 0.55 mm. CONCLUSION: Compared with humans, pigs have shorter left coronary artery trunks and branches; even the circumflex artery never reaches the posterior interventricular sulcus. Our findings are useful for the design of experimental hemodynamic and procedural models. PMID- 25140470 TI - Myocardial regeneration after implantation of porcine small intestinal submucosa in the left ventricle. AB - INTRODUCTION: Most cardiomyocytes do not regenerate after myocardial infarction. Porcine small intestinal submucosa has been shown to be effective in tissue repair. OBJECTIVE: To evaluate myocardial tissue regeneration and functional effects of SIS implantation in pigs after left ventriculotomy. METHODS: Fifteen pigs were assigned to two groups: porcine small intestinal submucosa (SIS) (N=10) and control (N=5). The SIS group underwent a mini sternotomy, left ventriculotomy and placement of a SIS patch. The control group underwent a sham procedure. Echocardiography was performed before and 60 days after the surgical procedure. Histological analysis was performed with hematoxylin-eosin stain and markers for actin 1A4, anti sarcomeric actin, connexin43 and factor VIII. RESULTS: Weight gain was similar in both groups. Echocardiography analysis revealed no difference between groups regarding end diastolic and systolic diameters and left ventricular ejection fraction, both pre (P=0.118, P=0.313, P=0.944) and post procedure (P=0.333, P=0.522, P=0.628). Both groups showed an increase in end diastolic (P<0,001 for both) and systolic diameter 60 days after surgery (P=0.005, SIS group and P=0.004, control group). New cardiomyocytes, blood vessels and inflammatory reactions were histologically identified in the SIS group. CONCLUSION: SIS implantation in pigs after left ventriculotomy was associated with angiomuscular regeneration and no damage in cardiac function. PMID- 25140472 TI - Preoperative therapy restores ventilatory parameters and reduces length of stay in patients undergoing myocardial revascularization. AB - INTRODUCTION: The frequency of surgical procedures has increased steadily in recent decades, including the myocardial revascularization. OBJECTIVES: To demonstrate the importance of physiotherapy in the preoperative period of cardiac surgery in relation to the reduction of hospital stay, changes in lung volumes and respiratory muscle strength. METHODS: We conducted a prospective study with patients undergoing myocardial revascularization, the Hospital das Clinicas da Universidade Estadual Paulista (UNESP)/Botucatu - SP. We evaluated 70 patients of both genders, aged between 40 and 75 years, subdivided into two groups: group I - 35 patients of both genders, who received a written protocol guidance, breathing exercises and respiratory muscle training in the preoperative period and group II - 35 patients of both genders, who received only orientation of the ward on the day of surgery. This study was approved by the Ethics Committee of UNESP / Botucatu - SP. RESULTS: Maximal inspiratory pressure in third postoperative day and fifth postoperative day and significant difference between groups, being better for the intervention group. Expiratory pressure was significant in fifth postoperative day in the intervention group compared to controls. The difference of length of hospital stay in the postoperative was found between the groups with shorter hospital stay in the group receiving preoperative therapy. CONCLUSION: Physical therapy plays an important role in the preoperative period, so that individuals in the intervention group more readily restored the parameters evaluated before surgery, in addition, there was a decrease in the time of the postoperative hospital stay. Thus, it is thought the cost-effectiveness of a program of preoperative physiotherapy. PMID- 25140474 TI - Left subclavian artery stenting: an option for the treatment of the coronary subclavian steal syndrome. AB - INTRODUCTION: The subclavian steal syndrome is characterized by the vertebral artery flow inversion, due to a stenotic lesion in the origin of the subclavian artery. The Coronary-subclavian Steal Syndrome is a variation of the Subclavian Steal Syndrome and is characterized by inversion of flow in the Internal Thracic artery that has been used as conduct in a myocardial revascularization. Its diagnosis must be suspected in patients with difference in pulse and arterial pressure in the upper limbs, that present with angina pectoris and that have done a myocardial revascularization. Its treatment must be a surgical bypass or a transluminal angioplasty. OBJECTIVE: The objective is to show the left subclavian artery stenting as a safe and effective method to treat the coronary-subclavian steal syndrome. METHODS: Historical prospective, non-randomized trial, through revision of the hospital records of the patients treated with the stenting of the left subclavian artery, from January 2006 to September 2012. RESULTS: In the mentioned period, 4.291 miocardial revascularizations were performed with the use of the left mammary artery, and 16 patients were identified to have the Coronary subclavian steal syndrome. All of them were submitted to endovascular treatment. The success rate was 100%; two patients experienced minor complications; none of them presented with major complications. Eleven of the 16 patients had ultrassonographic documentation of patent stent for at least one year; two patients lost follow up and other two died. CONCLUSION: The stenting of the left subclavian artery is a good option for the treatment of the Coronary-subclavian Steal Syndrome, with high level of technical and clinical success. PMID- 25140473 TI - Improvement in cardioplegic perfusion technique in single aortic clamping - initial results. AB - INTRODUCTION: The most common method used for myocardial protection is administering cardioplegic solution in the coronary circulation. Nevertheless, protection may be achieved by intermittent perfusion of the coronary system with patient's own blood. The intermittent perfusion may be performed by multiple sequences of clamping and opening of the aortic clamp or due single clamping and accessory cannulation of the aortic root as in the improved technique proposed in this study, reperfusion without the need for multiple clamping of the aorta. OBJECTIVE: To evaluate the clinical outcome and the occurrence of neurological events in in-hospital patients submitted to myocardial revascularization surgery with the "improved technique" of intermittent perfusion of the aortic root with single clamping. METHODS: This is a prospective, cross-sectional, observational study that describes a myocardial management technique that consists of intermittent perfusion of the aortic root with single clamping in which 50 patients (mean age 58.5 +/- 7.19 years old) have been submitted to the myocardial revasculrization surgery under the proposed technique. Clinical and laboratory variables, pre- and post-surgery, have been assessed. RESULTS: The mean peak level of post-surgery CKMB was 51.64 +/- 27.10 U/L in the second post-surgery and of troponin I was 3.35 +/- 4.39 ng/ml in the fourth post-surgery, within normal limits. No deaths have occurred and one patient presented mild neurological disorder. Hemodynamic monitoring has not indicated any changes. CONCLUSION: The myocardial revascularization surgery by perfusion with the improved technique with intermittent aortic root with single clamping proved to be safe, enabling satisfactory clinical results. PMID- 25140475 TI - Evolution of weight and height of children with congenital heart disease undergoing surgical treatment. AB - OBJECTIVE: To evaluate the height and weight development of children with congenital heart disease undergoing surgery with the goal of determining when they reach the threshold of normal development and whether there are differences between patients with developmental pattern below the level of normality preoperatively (z-score<-2 for the analyzed parameter) in comparison to the total group of cardiac patients. METHODS: We prospectively followed up 27 children undergoing operation into five time periods: preoperatively and at four subsequent outpatient appointments: 1st month, 3rd month, 6th month and 12th month after hospital discharge. The anthropometric parameters used were median z score (MZ), weight (WAZ), height (HAZ), subscapular skinfold (SSFAZ), upper arm circumference (UAC) and triceps skinfold (TSFAZ). The evolution assessment of the parameters was performed by analysis of variance and comparison with the general normal population from unpaired t test, both in the total group of cardiac patients, and in subgroups with preoperative parameters below the normal level (Zm<-2). RESULTS: In the total group there was no significant evolution of MZ of all parameters. WAZ was statistically lower than the normal population until the 1st month of follow-up (P=0.028); HAZ only preoperatively (P=0.044), SSFAZ in the first month (P=0.015) and at 12th month (P=0.038), UAC and TSFAZ were always statistically equal to the general population. In patients whose development was below the level of normality, there were important variation of WAZ (P=0.002), HAZ (P=0.001) and UAC (P=0.031) after the operation, and the WAZ was lower than the normal population until the 3rd month (P=0.015); HAZ and UAC, until the first month (P=0.024 and P=0.039 respectively), SSFAZ, up to the 12th month (P=0.005), the TSFAZ only preoperatively (P=0.011). CONCLUSION: The operation promoted the return to normalcy for those with heart disease in general within up to three months, but for the group of patients below normal developmental pattern of the return occurred within 12 months. PMID- 25140476 TI - The calcium paradox - what should we have to fear? AB - The calcium paradox was first mentioned in 1966 by Zimmerman et al. Thereafter gained great interest from the scientific community due to the fact of the absence of calcium ions in heart muscle cells produce damage similar to ischemia reperfusion. Although not all known mechanisms involved in cellular injury in the calcium paradox intercellular connection maintained only by nexus seems to have a key role in cellular fragmentation. The addition of small concentrations of calcium, calcium channel blockers, and hyponatraemia hypothermia are important to prevent any cellular damage during reperfusion solutions with physiological concentration of calcium. PMID- 25140477 TI - Cardiac risk stratification in cardiac rehabilitation programs: a review of protocols. AB - OBJECTIVE: Gather and describe general characteristics of different protocols of risk stratification for cardiac patients undergoing exercise. METHODS: We conducted searches in LILACS, IBECS, MEDLINE, Cochrane Library, and SciELO electronic databases, using the following descriptors: Cardiovascular Disease, Rehabilitation Centers, Practice Guideline, Exercise and Risk Stratification in the past 20 years. RESULTS: Were selected eight studies addressing methods of risk stratification in patients undergoing exercise. CONCLUSION: None of the methods described could cover every situation the patient can be subjected to; however, they are essential to exercise prescription. PMID- 25140478 TI - Vacuum-assisted drainage in cardiopulmonary bypass: advantages and disadvantages. AB - Systematic review of vacuum assisted drainage in cardiopulmonary bypass, demonstrating its advantages and disadvantages, by case reports and evidence about its effects on microcirculation. We conducted a systematic search on the period 1997-2012, in the databases PubMed, Medline, Lilacs and SciELO. Of the 70 selected articles, 26 were included in the review. Although the vacuum assisted drainage has significant potential for complications and requires appropriate technology and professionalism, prevailed in literature reviewed the concept that vacuum assisted drainage contributed in reducing the rate of transfusions, hemodilutions, better operative field, no significant increase in hemolysis, reduced complications surgical, use of lower prime and of smaller diameter cannulas. PMID- 25140479 TI - Biocompatibility of Ricinus communis polymer with addition of calcium carbonate compared to titanium. Experimental study in guinea pigs. AB - OBJECTIVE: The aim of the present investigation was to determine whether the difference in inflammatory tissue reaction between the Riccinus communis (castor) polymer with calcium carbonate and the titanium implant is statistically significant. METHODS: Thirty-two Cavia porcellus were allocated into four groups of eight animals each. We implanted the two types of materials in the retroperitoneal space of all the animals. They were euthanized at 7, 20, 30 and 40 days after surgery, and an histological study of the samples was conducted. RESULTS: All implants showed characteristics of chronic inflammation regardless of the material and timepoint of evaluation. There was no statistically significant difference between Pm+CaCO3 and Ti with regard to the presence of granulation tissue, tissue congestion, histiocytes, lymphocytes, neutrophils, giant cells, and fibrosis (P> 0.05). CONCLUSION: The castor oil polymer plus calcium carbonate implant was not statistically different from the titanium implant regarding inflammatory tissue reaction. PMID- 25140480 TI - The use of virtual resources in preoperative preparation of infrarenal aneurysms: exploring the OsiriX's potential. AB - INTRODUCTION: In the past few years, the increase of endovascular surgeons' interest on tomography image edition through softwares is marked specially when it concerns to its use on preoperatory study for endovascular aneurysm repair. It is presumed that the bigger the number of informations extracted from the tomography exam and its three-dimensional reconstruction, the smaller is the need of patient's exposure to contrast, as well as the its exposure and the surgical team to radiation. Concepts of image manipulation on the OsiriX software with volume reconstruction of tridimensional tomographic scans of virtual fluoroscopy were used. METHODS: Through manipulation of multi-slice tomography images under three-dimensional reconstruction on software, it was able to modify values of the exam's dose-irradiated distribution. These volume reconstruction presets were saved as Virtual Fluoroscopy, reproducible upon any OsiriX platform. It was able to construct a biplanar image appearing to the patient's operatory fluoroscopy. When compared to the intraoperatory angiography, the images were alike. DISCUSSION: Dose-irradiated distribution data manipulation allowed to visualize as opaque bone surfaces and transparent low-dose radiation's areas (viscerae). Thus, under previously marked renal arteries, it was possible to predict it's anatomical positioning related to visualization under real fluoroscopy. Foretelling the better positioning of the C-arm through this technique enables to obtain images with the minimum influence of parallax effect. It is believed that it supports to assess the renal arteries topographic positioning on a bi dimensional intraoperatory image. The need of frequent angiographies to localize the renal arteries is reduced, decreasing the exposure to contrast on vulnerable patients. PMID- 25140481 TI - Intracardiac embolization of inferior vena cava filter associated with right atrium perforation and cardiac tamponade. AB - Insertion of inferior vena cava filters has been well established in literature, reducing occurrence of pulmonary embolism after an episode of deep venous thrombosis in patients with contraindication to anticoagulation. There are a small number of complications related to procedure and embolization is rare. In this context, we described a case of intracardiac embolization associated with cardiac tamponade. PMID- 25140482 TI - Comment on "depression after CABG: a prospective study.". PMID- 25140484 TI - Condemnation to plagiarism. PMID- 25140485 TI - Brazilian Registry of Cardiovascular Surgery in Adults. From design to reality. PMID- 25140486 TI - Increasing isolated right heart chambers in second trimester ultrasound: always a warning sign? PMID- 25140487 TI - Associations between birth weight, preeclampsia and cognitive functions in middle aged adults. AB - Both reductions in birth weight and preeclampsia (PE) have been associated with decrements in scores on tests of intelligence in children and adolescents. We examined whether these decrements persist into middle adulthood and expand into other domains of cognitive functioning. Using data from the Early Determinants of Adult Health project and from the ancillary project, Fetal Antecedents of Major Depression and Cardiovascular Disease, we selected term same-sex sibling sets or singletons from these sets, from the New England Family Study (NEFS) and the Child Health and Development Studies (CHDS), discordant on either fetal growth or PE, to test the hypotheses that prenatal exposure to inflammation was associated with decrements in attention, learning and executive function 40 years later. Exposure was defined as a continuous measure of percentile birth weight for gestational age, reduced fetal growth (<20th percentile of birth weight for gestational age) or maternal PE. Given that the sample was comprised, in part, of sibling sets, the analyses were performed using mixed models to account for the inter-sibling correlations. Analyses were performed separately by study site (i.e. NEFS and CHDS). We found few statistically significant associations (suggesting a possible type II error) consistent with previous literature, suggesting that the associations with low birth weight do not persist into midlife. We discuss the possible reasons for the lack of associations, which include the possible mediating effects of the postnatal environment. PMID- 25140489 TI - The energy release rate of a pressurized crack in soft elastic materials: effects of surface tension and large deformation. AB - In this paper we present a theoretical study on how surface tension affects fracture of soft solids. In classical fracture theory, the resistance to fracture is partly attributed to the energy required to create new surfaces. Thus, the energy released to the crack tip must overcome the surface energy in order to propagate a crack. In soft materials, however, surface tension can cause significant deformation and can reduce the energy release rate for crack propagation by resisting the stretch of crack surfaces. We quantify this effect by studying the inflation of a penny-shaped crack in an infinite elastic body with applied pressure. To avoid numerical difficulty caused by singular fields near the crack tip, we derived an expression for the energy release rate which depends on the applied pressure, the surface tension, the inflated crack volume and the deformed crack area. This expression is evaluated using a newly developed finite element method with surface tension elements. Our calculation shows that, when the elasto-capillary number omega = sigma/Ea is sufficiently large, where sigma is the isotropic surface tension, E is the small strain Young's modulus and a is the initial crack radius, both the energy release rate and the crack opening displacement of an incompressible neo-Hookean solid are significantly reduced by surface tension. For a sufficiently high elasto-capillary number, the energy release rate can be negative for applied pressure less than a critical amount, suggesting that surface tension can cause crack healing in soft elastic materials. PMID- 25140488 TI - Effect of maternal coffee, smoking and drinking behavior on adult son's semen quality: prospective evidence from the Child Health and Development Studies. AB - Fetal exposure to caffeine is associated with adverse pregnancy outcomes. Animal and human studies suggest that caffeine may have effects on the developing reproductive system. Here we report on mothers' smoking, coffee and alcohol use, recorded during pregnancy, and semen quality in sons in the age group of 38-47 years. Subjects were a subset of the Child Health and Development Studies, a pregnancy cohort enrolled between 1959 and 1967 in the Kaiser Foundation Health Plan near Oakland, California. In 2005, adult sons participated in a follow-up study (n = 338) and semen samples were donated by 196 participants. Samples were analyzed for sperm concentration, motility and morphology according to the National Cooperative Reproductive Medicine Network (Fertile Male Study) Protocol. Mean sperm concentration was reduced by approximately 16 million sperms for sons with high prenatal exposure (5 cups of maternal coffee use per day) compared with unexposed sons (P-value for decreasing trend = 0.09), which translates to a proportionate reduction of 25%. Mean percent motile sperm decreased by approximately 7 points (P-value = 0.04), a proportionate decline of 13%, and mean percent sperm with normal morphology decreased by approximately 2 points (P-value = 0.01), a proportionate decline of 25%. Maternal cigarette and alcohol use were not associated with son's semen quality. Adjusting for son's contemporary coffee, alcohol and cigarette use did not explain the maternal associations. Findings for son's coffee intake and father's prenatal coffee, cigarette and alcohol use were non-significant and inconclusive. These results contribute to the evidence that maternal coffee use during pregnancy may impair the reproductive development of the male fetus. PMID- 25140490 TI - To assemble or fold? AB - This communication reports an elegant structure formation by an amide functionalized donor (D)-acceptor (A) dyad by stepwise folding and assembly. It adopts a folded conformation by intra-chain CT-interaction that subsequently dimerizes by inter-molecular H-bonding to produce a folded dimer (FD) with a DAAD stacking sequence. Incompatibility of the aromatic stacked face with MCH triggers macroscopic assembly by solvophobically driven edge-to-edge stacking of the FD with concomitant growth in the orthogonal direction by D-D pi-stacking leading to the formation of a reverse-vesicle. PMID- 25140493 TI - Prenatal diagnosis of Loeys-Dietz syndrome. PMID- 25140492 TI - Gas-phase synthesis and reactivity of Cu(+)-benzyne complexes. AB - Cu(+)-benzyne complexes bearing bidentate nitrogen ligands were synthesized in the gas phase for the first time using electrospray ionization mass spectrometry. The addition reactivity of copper-stabilized benzyne with amines was studied in the ion trap analyzer. The structures of products were identified by comparing their MS(n) data with authentic compounds obtained from another generation route. PMID- 25140494 TI - First experience with three-dimensional speckle tracking (3D wall motion tracking) in fetal echocardiography. AB - OBJECTIVES: Fetal cardiac function can be quantified by different methods. This is the first approach of real three-dimensional(3 D)-based speckle tracking echocardiography in the fetus to assess different cardiac strain parameters. METHODS: We present preliminary results of fetal global myocardial strain analyses. For fetal echocardiography a Toshiba Artida system was used. Based on an apical or basal four-chamber view of the fetal heart, raw data volumes with a high temporal resolution were acquired and digitally stored. RESULTS: 8 individual healthy fetuses with an echocardiogram performed between 21 and 37 weeks of gestation were included. The mean temporal resolution was 31.2 +/- 4.3 volumes per second (vps). Basic parameters such as longitudinal and circumferential strain as well as advanced 3 D myocardial motion patterns such as area strain, rotation, twist and torsion were assessed. CONCLUSION: Currently the assessment of fetal myocardial deformation parameters by 3 D speckle tracking seems to be technically feasible only in individual cases. In the future further development of this technique is necessary to improve its application in fetal echocardiography. PMID- 25140495 TI - A Comparison of the Diagnostic Accuracy and Reliability of Subjective Grading and Computer-Aided Assessment of Intranodal Vascularity in Differentiating Metastatic and Reactive Cervical Lymphadenopathy. AB - PURPOSE: Ultrasound is a well-established imaging modality in the assessment of malignant cervical lymphadenopathy. With the use of Doppler ultrasound, intranodal vascularity can be evaluated. However, the major limitation of ultrasound is operator dependency. Therefore, this study aimed to evaluate and compare the diagnostic accuracy and reliability of the subjective grading and computer-aided approach in assessing intranodal vascularity for the differentiation of benign and malignant lymph nodes. MATERIALS AND METHODS: The present study retrospectively assessed 99 power Doppler ultrasound images of cervical lymph nodes and evaluated the degree of intranodal vascularity using qualitative subjective grading (QSG) and quantitative computer-aided (QCA) methods. The diagnostic accuracy of the two methods in distinguishing metastatic and reactive nodes and their inter- and intra-rater reliability in assessing intranodal vascularity were evaluated and compared. RESULTS: The results showed that the QCA method was more accurate than the QSG method with a significantly higher sensitivity (67.8 % and 61.9 %, respectively, p < 0.05) and specificity (73.3 % and 57.3 %, respectively, p < 0.05). Using the intranodal vascularity index as determined by the QCA approach, the optimum cut-off to differentiate metastatic and reactive cervical lymph nodes was 32 %. The QCA method showed higher inter- and intra-rater reliability than the QSG method. CONCLUSION: In the assessment of the degree of intranodal vascularity, the QCA method was more accurate and reliable than the QSG method in distinguishing metastatic and reactive lymph nodes. PMID- 25140496 TI - Contrast-enhanced ultrasound and real-time elastography for the diagnosis of benign Leydig cell tumors of the testis - a single center report on 13 cases. AB - PURPOSE: To describe sonomorphological features in testicular Leydig cell tumors (LCTs) with a special focus on contrast-enhanced ultrasonography (CEUS) and real time elastography (RTE). PATIENTS AND METHODS: In a series of 186 patients with testicular surgery for neoplastic disease, 13 benign LCTs (in 12 patients) were histopathologically diagnosed. Preoperatively, all patients had been examined with a standardized protocol (high-resolution grayscale and color-coded ultrasonography, CEUS). 5 patients underwent RTE. In CEUS, the filling time of the lesion was compared to that of 14 size-matched germ cell tumors (GCT). RESULTS: 10/13 LCTs had a size of < 10 mm, and a sharply demarcated hypoechoic appearance was typical (10/13). Color-coded ultrasonography detected signals in 8 lesions, while CEUS showed clear hypervascularization in all. LCTs had a significantly shorter filling time than GCTs (p < 0.0005), with 9/13 LCTs being completely filled within 4 s. In RTE, all 5 examined lesions were clearly "harder" than the surrounding testicular tissue. CONCLUSION: Contrary to some earlier reports, we could demonstrate marked hypervascularization in LCTs. This feature clearly allows for the differentiation of a small LCT from focal scars. However, it may only be visible on CEUS. In CEUS, LCT is suggested by the findings of a short filling time or by a circumferential vessel with a rapid centripetal filling, combined with a "harder" appearance in RTE. These features along with the findings of a small and peripherally situated hypoechoic tumor would justify an operative strategy with frozen section examination and possibly organ sparing surgery instead of orchiectomy. PMID- 25140497 TI - Normal values for transbulbar sonography and magnetic resonance imaging of the optic nerve sheath diameter (ONSD) in children and adolescents. AB - PURPOSE: To establish normal values of the optic nerve sheath diameter (ONSD) in children and adolescents for transbulbar sonography and magnetic resonance imaging. MATERIALS AND METHODS: In 99 children and adolescents (age: 5.6 - 18.6 years, mean: 12 years) without neurologic or ophthalmologic disease, measurements of the ONSD with transbulbar sonography were performed. For comparison 59 children and adolescents (age: 5.1 - 17.4 years, mean 12.3 years) with a normal MR examination of the brain had measurements of the ONSD on a T2-weighted thin section sequence of the orbit. Besides establishing modality-related normal values, age dependency, accuracy and reproducibility of measurements were assessed. RESULTS: Overall the mean ONSD was 5.75 +/- 0.52 mm for transbulbar sonography and 5.69 +/- 0.31 mm for MRI. There was no statistical significance between the 95 % percentiles and age for both transbulbar sonography (p = 0.332) and MRI (p = 0.336). As a parameter for the reproducibility of measurements, the repeatability coefficient (RC) was between 0.34 mm and 0.46 mm. The concordance correlation coefficient (CCC) values revealed a high agreement between readers both for transbulbar sonography (0.868) and MRI (0.796). CONCLUSION: Normal values for ONSD in children and adolescents found in this study are significantly higher than assumed. The values found for transbulbar sonography are confirmed by comparable results for MR measurements. A precise sonographic measurement technique and the consideration of normal values found hereby are essential for correct interpretation of ONSD measurements in children and adolescents. PMID- 25140498 TI - Noninvasive Prenatal Diagnosis of Hypohidrotic Ectodermal Dysplasia by Tooth Germ Sonography. AB - PURPOSE: Hypohidrotic ectodermal dysplasia, a potentially life-threatening heritable disorder, may be recognized already in utero by characteristic features such as oligodontia and mandibular hypoplasia. As therapeutic options and prognosis depend on the time point of diagnosis, early recognition was attempted during routine prenatal ultrasound examinations. SUBJECTS AND METHODS: Fetuses of nine pregnant women (one triplet and eight singleton pregnancies) with family histories of hypohidrotic ectodermal dysplasia were investigated by sonography between the 20th and 24th week of gestation. RESULTS: In 4 male and 2 female fetuses reduced amounts of tooth germs were detected, whereas 5 fetal subjects showed the normal amount. Three-dimensional ultrasound evaluation revealed mandibular hypoplasia in 5 of the 6 fetuses with oligodontia. Molecular genetic analysis and/or clinical findings after birth confirmed the prenatal sonographic diagnosis in each subject. CONCLUSION: In subjects with a family history of hypohidrotic ectodermal dysplasia, the diagnosis of this rare condition can be established noninvasively by sonography in the second trimester of pregnancy. Early recognition of the disorder may help to prevent dangerous hyperthermic episodes in infancy and may allow timely therapeutic interventions. PMID- 25140499 TI - The scientific literature on Limnoperna fortunei (Dunker 1857) from 1982 to 2012. AB - Limnoperna fortunei (golden mussel) is a freshwater bivalve native to Southeast Asia, but is becoming an invasive species in several aquatic ecosystems in the world. In this study, a scientometric analysis was performed to identify the patterns, trends and gaps of knowledge for this invasive species. A survey of the published literature was conducted using the database of the Thomson Institute for Scientific Information (ISI). A total of 107 papers were surveyed that were published between 1982 and 2012 in 60 journals. The number of papers on L. fortunei over the years has increased, especially within the last eight years of the study period. Argentina, Brazil, and Japan are the countries that contributed the most papers to the literature on invasive bivalve. The majority of papers were field-observational studies. Among some important gaps that need to be addressed are the relatively small number and/or lack of studies conducted in the native countries and in countries invaded by L. fortunei, the lack of internationally collaborative publications in these countries, as well as a low number of internationally collaborative studies. PMID- 25140500 TI - Growth and intestinal morphology of juvenile pacu Piaractus mesopotamicus (Holmberg 1887) fed dietary prebiotics (mannanoligosaccharides - MOS). AB - Intensification of aquaculture production systems exposes fish to numerous stressors, which may negatively affect their growth and limit profitability of aquaculture systems. This study determined effects of increasing levels of dietary mannanoligosaccharides on growth and intestine morphology of pacu. Fish (44.04 g) were randomly distributed into 32 tanks (500 L; 10 fishes per tank) and fed during 63 days with a commercial diet supplemented with 0.0; 0.2; 0.4; 0.6; 0.8; 1.0; 1.5 and 2.0% dietary mannanoligosaccharides. Growth parameters did not differ (P>0.05) between fish fed control diet and mannanoligosaccharide supplemented diets. Intestinal villi perimeter was performed in fish fed control diet, 0.4 and 1.5% dietary mannanoligosaccharides and also showed no differences (P>0.05) between treatments. Dietary supplementation of mannanoligosaccharides unclear did not have effects on pacu. Studies on the characterization of intestinal microbiota together with experiment that reproduce commercial fish production systems rearing conditions are necessary to determine the effective use of this dietary supplement for the species. PMID- 25140501 TI - Magnetic Parkia pendula seed gum as matrix for Concanavalin A lectin immobilization and its application in affinity purification. AB - The present work aimed to magnetize Parkia pendula seeds gum and use it as a matrix for Concanavalin A covalent immobilization. This composite was applied in affinity purification of glycoconjugates. Parkia pendula seeds were hydrated and the gum provenient from the supernatant was precipitated and washed with ethanol and dried. The gum was magnetized in co-precipitation using solutions of Fe+2 and Fe+3. Matrix activation was accomplished with NaIO4. Magnetized Parkia pendula seeds gum with covalently immobilized Concanavalin A was used as an affinity matrix for the recognition of bovine serum fetuin glycoprotein. Fetuin elution was carried out with a solution of glucose (300mM) and evaluated through SDS PAGE. The efficiency of lectin immobilization and fetuin purification were 63% and 14%, respectively. These results indicate that the composite produced is a promising magnetic polysaccharide matrix for lectins immobilization. Thus, such system can be applied for affinity purification allowing an easy recovery by magnetic field. PMID- 25140502 TI - First ediacaran fauna occurrence in northeastern Brazil (jaibaras basin, ?ediacaran-cambrian): preliminary results and regional correlation. AB - This study reports the first known occurrence of the Ediacaran fauna in northeastern Brazil (at Pacuja Municipality, northwestern state of Ceara) and presents preliminary interpretations of its significance. Regional correlation indicates that the fossils originated in the Jaibaras Basin and that they may represent a new geological system. The depositional environment can be attributed to a fluviomarine system. Nine Ediacaran species can be identified, including members of pandemic groups (e.g., Charniodiscus arboreus Glaessner, 1959; ?Charniodiscus concentricus Ford, 1958; Cyclomedusa davidi Sprigg, 1947; Ediacaria flindersi Sprigg, 1947; and Medusinites asteroides Sprigg, 1949) and endemic groups (e.g., Kimberella quadrata Glaessner & Wade, 1966; Palaeophragmodictya reticulata Gehling & Rigby, 1996; Parvancorina minchami Glaessner, 1958; and Pectinifrons abyssalis Bamforth, Narbonne, Anderson, 2008). Three ichnogenera are also present: Arenicolites Salter, 1857; Palaeophycus Hall, 1987; and Planolites Nicholson, 1873. The relative age of the deposits is between ?Ediacaran and Cambrian, and the fauna resembles the White Sea Assemblage. The bioturbation presents typical unbranched Ediacaran ichnogenera with little depth in the substrate. This previously unknown occurrence of the Ediacaran fauna reinforces the importance of the state of Ceara to Brazilian and global palaeontology. PMID- 25140503 TI - Thyroid gland development in Rachycentron canadum during early life stages. AB - The aim of this study was to describe the ontogeny of thyroid follicles in cobia Rachycentron canadum. Larvae were sampled daily (n=15 - 20) from hatching until 15 dah (days after hatching). Following, larvae were sampled every two days by 28 dah; a new sample was taken at 53 dah. The samples were dehydrated, embedded in Paraplast, and sections of 3 um were dewaxed, rehydrated and stained with HE and PAS. A single follicle was already present 1 dah and three follicles were found 8 dah. The number of follicles increased up to 19 on 53 dah. The diameter of follicles and follicular cell height were lower 1 dah (6.83 +/- 1.00 and 4.6 +/- 0.01 um), but increased from 8 dah (24.03 +/- 0.46 um e 6.43 +/- 0.46 um). From 8 dah, the presence of reabsorption vesicles was observed in the colloid and from the 19 dah some follicles did not present colloid. The early thyroid follicle appearance in cobia larvae as well as the high quantity of follicles without colloid and/or with vesicles even after the metamorphosis, might be the explanation of the fast growth of the cobia. PMID- 25140504 TI - Probiotics protect the intestinal wall of morphological changes caused by malnutrition. AB - This study sought to morphometrically analyze the jejunal wall of protein malnourished rats administered a probiotic supplement. The sample consisted of recently weaned Wistar rats (Rattus norvegicus) distributed among four groups: animals given a commercial diet (G1, n = 4); animals given the same ration as G1 plus a probiotic supplement (G2, n = 4); animals given a 4% protein diet (G3, n = 4); and animals given the same ration as G3 plus a probiotic supplement (G4, n = 4). After 12 weeks, part of the jejunum was harvested and subjected to routine histological processing. Transverse sections with a thickness of 3 um were stained with HE, and histochemical techniques were used to assay for glycoconjugates, including staining with periodic acid-Schiff (PAS) + diastase, Alcian Blue (AB) solution at pH 2.5, and Alcian Blue solution at pH 1.0. Morphometric analysis of the bowel wall showed that the probiotic culture used in this study induced hypertrophy of several layers of the jejunal wall in well nourished animals and reduced the bowel wall atrophy usually observed in protein malnourished animals. Neither malnutrition nor the use of probiotics altered the relationship between the number of goblet cells and the number of enterocytes. PMID- 25140505 TI - Re-induction of desiccation tolerance after germination of Cedrela fissilis Vell. seeds. AB - This work aimed to characterize the re-induction of desiccation tolerance (DT) in germinated seeds, using polyethylene glycol (PEG 8000). Cell changes were investigated through cytological assays (cell viability and transmission electronic microscopy) as well as DNA integrity during loss and re-establishment of DT. The loss of DT was characterized by drying germinated seeds with different radicle lengths (1, 2, 3, 4 and 5 mm) in silica gel, decreasing the moisture content to ten percentage points intervals, followed by pre-humidification (100% RH / 24 h) and rehydration. To re-induce DT, germinated seeds were treated for 72 h with PEG (-2.04 MPa) and PEG (-2.04 MPa) + ABA (100 uM) before dehydration. Germinated seeds did not tolerate desiccation to 10% moisture content, irrespectively of the radicle length. However, when incubated in PEG, those with 1 and 2 mm long radicle attained 71% and 29% survival, respectively. The PEG+ABA treatment was efficient to re-establish DT in seeds with 1 mm long radicles (100% survival). The ultrastructural assays of the cells of germinated seeds with 2 and 5 mm length confirmed the obtained physiological results. Germinated seeds of C. fissilis constitute a useful tool for desiccation tolerance investigations. PMID- 25140506 TI - CD56 antibody: old-fashioned or still trendy in endocrine lung tumors. AB - BACKGROUND: In 2010, the World Health Organization published a new classification of the endocrine tumors based on the mitotic rate and index. Concerning lung endocrine tumors, the classification of 2004 remains acceptable and widely approved. We noticed in many publications that the most used antibodies in these tumors are chromogranin and synaptophysin. This finding let us wonder about the diagnostic utility of the CD56 antibody which is widely used in our department. MATERIAL AND METHODS: Sixty-nine endocrine lung cancers were diagnosed over a 12 month period in our Department of Pathology. Immunohistochemical technique using the three antibodies: chromogranin, synaptophysin, and CD56 was performed. The sensitivity of the three antibodies was performed using the ratio: true negative cases/true negative cases + false positive cases. The specificity wasn't performed because the antibodies were used only in endocrine tumors. The comparison of the different percentages of expression of the three antibodies was made by the SPSS software 22.0. RESULTS: The sensitivity of the chromogranin, synpatophysin, and CD56 accounted for 69%, 77%, and 98%, respectively. The mean percentage of immunoreactive cells with CD56 was 70% towards 15% and 20% with chromogranin and synaptophysin antibodies, respectively. The comparison of the percentages of expression showed a significant statistical difference between the expression of CD56 versus synaptophysin and CD56 versus chromogranin with P<0.001. CONCLUSION: CD56 antibody seems to be of diagnostic value in endocrine lung tumors with the highest sensitivity. This fact highlights the necessity of using it as a first-line neuroendocrine marker in association to chromogranin which is considered as the most specific endocrine antibody. PMID- 25140507 TI - Perioperative regional anesthesia fellowships: a blueprint for success. PMID- 25140508 TI - Cervical paravertebral block for elbow and wrist surgery: the jury verdict may be neither easy nor popular. PMID- 25140509 TI - Evaluation of a task-specific checklist and global rating scale for ultrasound guided regional anesthesia. AB - Checklists and global rating scales (GRSs) are used for assessment of anesthesia procedural skills. The purpose of this study was to evaluate the reliability and validity of a recently proposed assessment tool comprising a checklist and GRS specific for ultrasound-guided regional anesthesia. METHODS: In this prospective, fully crossed study, we videotaped 30 single-target nerve block procedures performed by anesthesia trainees. Following pilot assessment and observer training, videos were assessed in random order by 6 blinded, expert observers. Interrater reliability was evaluated with intraclass correlation coefficients (ICCs) based on a 2-way random-effects model that took into account both agreement and correlation between observer results. Construct validity and feasibility were also evaluated. RESULTS: The ICC between assessors' total scores was 0.44 (95% confidence interval, 0.27-0.62). All 6 observers scored "experienced trainees" higher than "inexperienced trainees" (median total score 76.7 vs 54.2, P = 0.01), supporting the test's construct validity. The median time to assess the videos was 4 minutes 29 seconds. CONCLUSIONS: This is the first study to evaluate the reliability and validity of a combined checklist and GRS for ultrasound-guided regional anesthesia using multiple observers and taking into account both absolute agreement and correlation in determining the ICC of 0.44 for interrater reliability. There was evidence to support construct validity. PMID- 25140510 TI - Accuracy and consistency of modern elastomeric pumps. AB - Continuous peripheral nerve blockade has become a popular method of achieving postoperative analgesia for many surgical procedures. The safety and reliability of infusion pumps are dependent on their flow rate accuracy and consistency. Knowledge of pump rate profiles can help physicians determine which infusion pump is best suited for their clinical applications and specific patient population. Several studies have investigated the accuracy of portable infusion pumps. Using methodology similar to that used by Ilfeld et al, we investigated the accuracy and consistency of several current elastomeric pumps. PMID- 25140511 TI - Pourfour du petit syndrome after supraclavicular catheter discontinuation. PMID- 25140512 TI - Improving transversus abdominis plane block safety. PMID- 25140513 TI - "Wrong side" sticker/dressing to help reduce wrong-sided nerve blocks. PMID- 25140514 TI - Redefining the adductor canal block. PMID- 25140515 TI - Generation and characterization of the first immortalized alpaca cell line suitable for diagnostic and immunization studies. AB - Raising of alpacas as exotic livestock for wool and meat production and as companion animals is growing in importance in the United States, Europe and Australia. Furthermore the alpaca, as well as the rest of the camelids, possesses the peculiarity of producing single-chain antibodies from which nanobodies can be generated. Nanobodies, due to their structural simplicity and reduced size, are very versatile in terms of manipulation and bio-therapeutic exploitation. In fact the biotech companies involved in nanobody production and application continue to grow in number and size. Hence, the development of reagents and tools to assist in the further growth of this new scientific and entrepreneurial reality is becoming a necessity. These are needed mainly to address alpaca disease diagnosis and prophylaxis, and to develop alpaca immunization strategies for nanobody generation. For instance an immortalized alpaca cell line would be extremely valuable. In the present work the first stabilized alpaca cell line from alpaca skin stromal cells (ASSCs) was generated and characterized. This cell line was shown to be suitable for replication of viruses bovine herpesvirus-1, bovine viral diarrhea virus and caprine herpesvirus-1 and the endocellular parasite Neospora caninum. Moreover ASSCs were easy to transfect and transduce by several methods. These two latter characteristics are extremely useful when recombinant antigens need to be produced in a host homologous system. This work could be considered as a starting point for the expansion of the biotechnologies linked to alpaca farming and industry. PMID- 25140517 TI - The gait disorder in downbeat nystagmus syndrome. AB - BACKGROUND: Downbeat nystagmus (DBN) is a common form of acquired fixation nystagmus with key symptoms of oscillopsia and gait disturbance. Gait disturbance could be a result of impaired visual feedback due to the involuntary ocular oscillations. Alternatively, a malfunction of cerebellar locomotor control might be involved, since DBN is considered a vestibulocerebellar disorder. METHODS: Investigation of walking in 50 DBN patients (age 72 +/- 11 years, 23 females) and 50 healthy controls (HS) (age 70 +/- 11 years, 23 females) using a pressure sensitive carpet (GAITRite). The patient cohort comprised subjects with only ocular motor signs (DBN) and subjects with an additional limb ataxia (DBNCA). Gait investigation comprised different walking speeds and walking with eyes closed. RESULTS: In DBN, gait velocity was reduced (p<0.001) with a reduced stride length (p<0.001), increased base of support (p<0.050), and increased double support (p<0.001). Walking with eyes closed led to significant gait changes in both HS and DBN. These changes were more pronounced in DBN patients (p<0.001). Speed-dependency of gait variability revealed significant differences between the subgroups of DBN and DBNCA (p<0.050). CONCLUSIONS: (I) Impaired visual control caused by involuntary ocular oscillations cannot sufficiently explain the gait disorder. (II) The gait of patients with DBN is impaired in a speed dependent manner. (III) Analysis of gait variability allows distinguishing DBN from DBNCA: Patients with pure DBN show a speed dependency of gait variability similar to that of patients with afferent vestibular deficits. In DBNCA, gait variability resembles the pattern found in cerebellar ataxia. PMID- 25140518 TI - Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans. AB - Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol induced neurotoxicity are still poorly understood despite numerous studies. Thus, we hypothesized that activated microglial cells with elevated AGE-albumin levels play an important role in promoting alcohol-induced neurodegeneration. Our results revealed that microglial activation and neuronal damage were found in the hippocampus and entorhinal cortex following alcohol treatment in a rat model. Increased AGE-albumin synthesis and secretion were also observed in activated microglial cells after alcohol exposure. The expressed levels of receptor for AGE (RAGE)-positive neurons and RAGE-dependent neuronal death were markedly elevated by AGE-albumin through the mitogen activated protein kinase pathway. Treatment with soluble RAGE or AGE inhibitors significantly diminished neuronal damage in the animal model. Furthermore, the levels of activated microglial cells, AGE albumin and neuronal loss were significantly elevated in human brains from alcoholic indivisuals compared to normal controls. Taken together, our data suggest that increased AGE-albumin from activated microglial cells induces neuronal death, and that efficient regulation of its synthesis and secretion is a therapeutic target for preventing alcohol-induced neurodegeneration. PMID- 25140519 TI - Asante Calcium Green and Asante Calcium Red--novel calcium indicators for two photon fluorescence lifetime imaging. AB - For a comprehensive understanding of cellular processes and potential dysfunctions therein, an analysis of the ubiquitous intracellular second messenger calcium is of particular interest. This study examined the suitability of the novel Ca2+-sensitive fluorescent dyes Asante Calcium Red (ACR) and Asante Calcium Green (ACG) for two-photon (2P)-excited time-resolved fluorescence measurements. Both dyes displayed sufficient 2P fluorescence excitation in a range of 720-900 nm. In vitro, ACR and ACG exhibited a biexponential fluorescence decay behavior and the two decay time components in the ns-range could be attributed to the Ca(2+)-free and Ca(2+)-bound dye species. The amplitude weighted average fluorescence decay time changed in a Ca(2+)-dependent way, unraveling in vitro dissociation constants K(D) of 114 nM and 15 nM for ACR and ACG, respectively. In the presence of bovine serum albumin, the absorption and steady-state fluorescence behavior of ACR was altered and its biexponential fluorescence decay showed about 5-times longer decay time components indicating dye-protein interactions. Since no ester derivative of ACG was commercially available, only ACR was evaluated for 2P-excited fluorescence lifetime imaging microscopy (2P-FLIM) in living cells of American cockroach salivary glands. In living cells, ACR also exhibited a biexponential fluorescence decay with clearly resolvable short (0.56 ns) and long (2.44 ns) decay time components attributable to the Ca(2+)-free and Ca(2+)-bound ACR species. From the amplitude-weighted average fluorescence decay times, an in situ K(D) of 180 nM was determined. Thus, quantitative [Ca(2+)]i recordings were realized, unraveling a reversible dopamine induced [Ca(2+)]i elevation from 21 nM to 590 nM in salivary duct cells. It was concluded that ACR is a promising new Ca(2+) indicator dye for 2P-FLIM recordings applicable in diverse biological systems. PMID- 25140520 TI - Metagenomic survey for viruses in Western Arctic caribou, Alaska, through iterative assembly of taxonomic units. AB - Pathogen surveillance in animals does not provide a sufficient level of vigilance because it is generally confined to surveillance of pathogens with known economic impact in domestic animals and practically nonexistent in wildlife species. As most (re-)emerging viral infections originate from animal sources, it is important to obtain insight into viral pathogens present in the wildlife reservoir from a public health perspective. When monitoring living, free-ranging wildlife for viruses, sample collection can be challenging and availability of nucleic acids isolated from samples is often limited. The development of viral metagenomics platforms allows a more comprehensive inventory of viruses present in wildlife. We report a metagenomic viral survey of the Western Arctic herd of barren ground caribou (Rangifer tarandus granti) in Alaska, USA. The presence of mammalian viruses in eye and nose swabs of 39 free-ranging caribou was investigated by random amplification combined with a metagenomic analysis approach that applied exhaustive iterative assembly of sequencing results to define taxonomic units of each metagenome. Through homology search methods we identified the presence of several mammalian viruses, including different papillomaviruses, a novel parvovirus, polyomavirus, and a virus that potentially represents a member of a novel genus in the family Coronaviridae. PMID- 25140521 TI - Associations between longer habitual day napping and non-alcoholic fatty liver disease in an elderly Chinese population. AB - CONTEXT: Both longer habitual day napping and Non-Alcoholic Fatty Liver Disease (NAFLD) are associated with diabetes and inflammation, but the association between day napping and NAFLD remains unexplored. OBJECTIVE: To investigate the association between the duration of habitual day napping and NAFLD in an elderly Chinese population and to gain insight into the role of inflammatory cytokines in this association. DESIGN AND SETTING: We conducted a series of cross-sectional studies of the community population in Chongqing, China, from 2011 to 2012. PARTICIPANTS: Among 6998 participants aged 40 to 75 years, 6438 eligible participants were included in the first study and analyzed to observe the association between day napping duration and NAFLD. In a separate study, 80 non nappers and 90 nappers were selected to identify the role of inflammatory cytokines in this association. Logistic regression models were used to examine the odds ratios (ORs) of day nap duration with NAFLD. RESULTS: Day nappers had a significantly higher prevalence of NAFLD (P<0.001). Longer day napping duration was associated in a dose-dependent manner with NAFLD (P trend <0.001). After adjustment for potential confounders, the ORs were 1.67 (95% CI 1.13-2.46) for those reporting 0.5-1 h and 1.49 (95% CI 1.01-2.19) for those reporting >1 h of day napping compared with individuals who did not take day naps (all P<0.05). Longer-duration day nappers had higher levels of IL-6 and progranulin (PGRN) but lower levels of Secreted frizzled-related protein-5 (SFRP5, all P trend <0.001). After adjusting for IL-6, PGRN, and SFRP5, the association between day napping duration and NAFLD disappeared (all P>0.05). CONCLUSION: Longer day napping duration is associated with a higher prevalence of NAFLD, and inflammatory cytokines may be an essential link between day napping and NAFLD. PMID- 25140522 TI - Development of on-chip multi-imaging flow cytometry for identification of imaging biomarkers of clustered circulating tumor cells. AB - An on-chip multi-imaging flow cytometry system has been developed to obtain morphometric parameters of cell clusters such as cell number, perimeter, total cross-sectional area, number of nuclei and size of clusters as "imaging biomarkers", with simultaneous acquisition and analysis of both bright-field (BF) and fluorescent (FL) images at 200 frames per second (fps); by using this system, we examined the effectiveness of using imaging biomarkers for the identification of clustered circulating tumor cells (CTCs). Sample blood of rats in which a prostate cancer cell line (MAT-LyLu) had been pre-implanted was applied to a microchannel on a disposable microchip after staining the nuclei using fluorescent dye for their visualization, and the acquired images were measured and compared with those of healthy rats. In terms of the results, clustered cells having (1) cell area larger than 200 um2 and (2) nucleus area larger than 90 um2 were specifically observed in cancer cell-implanted blood, but were not observed in healthy rats. In addition, (3) clusters having more than 3 nuclei were specific for cancer-implanted blood and (4) a ratio between the actual perimeter and the perimeter calculated from the obtained area, which reflects a shape distorted from ideal roundness, of less than 0.90 was specific for all clusters having more than 3 nuclei and was also specific for cancer-implanted blood. The collected clusters larger than 300 um2 were examined by quantitative gene copy number assay, and were identified as being CTCs. These results indicate the usefulness of the imaging biomarkers for characterizing clusters, and all of the four examined imaging biomarkers-cluster area, nuclei area, nuclei number, and ratio of perimeter-can identify clustered CTCs in blood with the same level of preciseness using multi-imaging cytometry. PMID- 25140524 TI - Is rumination after bereavement linked with loss avoidance? Evidence from eye tracking. AB - Rumination is a risk factor in adjustment to bereavement. It is associated with and predicts psychopathology after loss. Yet, the function of rumination in bereavement remains unclear. In the past, researchers often assumed rumination to be a maladaptive confrontation process. However, based on cognitive avoidance theories of worry in generalised anxiety disorder (GAD) and rumination after post traumatic stress disorder (PTSD), others have suggested that rumination may serve to avoid painful aspects of the loss, thereby contributing to complicated grief. To examine if rumination is linked with loss avoidance, an eye-tracking study was conducted with 54 bereaved individuals (27 high and 27 low ruminators). On 24 trials, participants looked for 10 seconds at a picture of the deceased and a picture of a stranger, randomly combined with negative, neutral or loss-related words. High ruminators were expected to show initial vigilance followed by subsequent disengagement for loss stimuli (i.e., picture deceased with a loss word) in the first 1500 ms. Additionally, we expected high ruminators to avoid these loss stimuli and to show attentional preference for non-loss-related negative stimuli (i.e., picture stranger with a negative word) on longer exposure durations (1500-10000 ms). Contrary to expectations, we found no evidence for an effect of rumination on vigilance and disengagement of loss stimuli in the first 1500 ms. However, in the 1500-10000 ms interval, high ruminators showed shorter gaze times for loss stimuli and longer gaze times for negative (and neutral) non loss-related stimuli, even when controlling for depression and complicated grief symptom levels. Effects of rumination on average fixation times mirrored these findings. This suggests that rumination and loss avoidance are closely associated. A potential clinical implication is that rumination and grief complications after bereavement may be reduced through the use of exposure and acceptance-based therapeutic techniques. PMID- 25140523 TI - Does mortality vary between Asian subgroups in New Zealand: an application of hierarchical Bayesian modelling. AB - The aim of this paper was to see whether all-cause and cause-specific mortality rates vary between Asian ethnic subgroups, and whether overseas born Asian subgroup mortality rate ratios varied by nativity and duration of residence. We used hierarchical Bayesian methods to allow for sparse data in the analysis of linked census-mortality data for 25-75 year old New Zealanders. We found directly standardised posterior all-cause and cardiovascular mortality rates were highest for the Indian ethnic group, significantly so when compared with those of Chinese ethnicity. In contrast, cancer mortality rates were lowest for ethnic Indians. Asian overseas born subgroups have about 70% of the mortality rate of their New Zealand born Asian counterparts, a result that showed little variation by Asian subgroup or cause of death. Within the overseas born population, all-cause mortality rates for migrants living 0-9 years in New Zealand were about 60% of the mortality rate of those living more than 25 years in New Zealand regardless of ethnicity. The corresponding figure for cardiovascular mortality rates was 50%. However, while Chinese cancer mortality rates increased with duration of residence, Indian and Other Asian cancer mortality rates did not. Future research on the mechanisms of worsening of health with increased time spent in the host country is required to improve the understanding of the process, and would assist the policy-makers and health planners. PMID- 25140525 TI - Thermal, chemical and pH induced unfolding of turmeric root lectin: modes of denaturation. AB - Curcuma longa rhizome lectin, of non-seed origin having antifungal, antibacterial and alpha-glucosidase inhibitory activities, forms a homodimer with high thermal stability as well as acid tolerance. Size exclusion chromatography and dynamic light scattering show it to be a dimer at pH 7, but it converts to a monomer near pH 2. Circular dichroism spectra and fluorescence emission maxima are virtually indistinguishable from pH 7 to 2, indicating secondary and tertiary structures remain the same in dimer and monomer within experimental error. The tryptophan environment as probed by acrylamide quenching data yielded very similar data at pH 2 and pH 7, implying very similar folding for monomer and dimer. Differential scanning calorimetry shows a transition at 350.3 K for dimer and at 327.0 K for monomer. Thermal unfolding and chemical unfolding induced by guanidinium chloride for dimer are both reversible and can be described by two-state models. The temperatures and the denaturant concentrations at which one-half of the protein molecules are unfolded, are protein concentration-dependent for dimer but protein concentration-independent for monomer. The free energy of unfolding at 298 K was found to be 5.23 Kcal mol-1 and 14.90 Kcal mol-1 for the monomer and dimer respectively. The value of change in excess heat capacity upon protein denaturation (DeltaCp) is 3.42 Kcal mol-1 K-1 for dimer. The small DeltaCp for unfolding of CLA reflects a buried hydrophobic core in the folded dimeric protein. These unfolding experiments, temperature dependent circular dichroism and dynamic light scattering for the dimer at pH 7 indicate its higher stability than for the monomer at pH 2. This difference in stability of dimeric and monomeric forms highlights the contribution of inter-subunit interactions in the former. PMID- 25140528 TI - Integrating basic science without integrating basic scientists: reconsidering the place of individual teachers in curriculum reform. AB - The call for integration of the basic and clinical sciences plays prominently in recent conversations about curricular change in medical education; however, history shows that, like other concepts related to curricular reform, integration has been continually revisited, leading to incremental change but no meaningful transformation. To redress this cycle of "change without difference," the medical education community must reexamine the approach that dominates medical education reform efforts and explore alternative perspectives that may help to resolve the cyclical "problem" of recommending but not effecting integration. To provide a different perspective on implementing integration, the authors of this Perspective look to the domain of educational change as an approach to examining the transitions that occur within complex and evolving environments. This area of literature both acknowledges the multiple levels involved in change and emphasizes the need not only to address systemic structure but also to prioritize individuals during times of transition. The struggle to implement curricular integration in medical education may stem from the fact that reform efforts appear to focus largely on transformation at the level of curricular structure as opposed to considering what learning needs to occur at each level of change and highlighting the individual as the educational change literature suggests. To bring appropriate attention to the place of individual educators, especially basic scientists, the medical education community should explore how the mandate to integrate clinically relevant material may impact these faculty and the teaching of their domains. PMID- 25140527 TI - Transforming growth factor-beta1 signaling represses testicular steroidogenesis through cross-talk with orphan nuclear receptor Nur77. AB - Transforming growth factor- beta1 (TGF-beta1) has been reported to inhibit luteinizing hormone (LH) mediated-steroidogenesis in testicular Leydig cells. However, the mechanism by which TGF-beta1 controls the steroidogenesis in Leydig cells is not well understood. Here, we investigated the possibility that TGF beta1 represses steroidogenesis through cross-talk with the orphan nuclear receptor Nur77. Nur77, which is induced by LH/cAMP signaling, is one of major transcription factors that regulate the expression of steroidogenic genes in Leydig cells. TGF-beta1 signaling inhibited cAMP-induced testosterone production and the expression of steroidogenic genes such as P450c17, StAR and 3beta-HSD in mouse Leydig cells. Further, TGF-beta1/ALK5 signaling repressed cAMP-induced and Nur77-activated promoter activity of steroidogenic genes. In addition, TGF beta1/ALK5-activated Smad3 repressed Nur77 transactivation of steroidogenic gene promoters by interfering with Nur77 binding to DNA. In primary Leydig cells isolated from Tgfbr2flox/flox Cyp17iCre mice, TGF-beta1-mediated repression of cAMP-induced steroidogenic gene expression was significantly less than that in primary Leydig cells from Tgfbr2flox/flox mice. Taken together, these results suggest that TGF-beta1/ALK5/Smad3 signaling represses the expression of steroidogenic genes via the suppression of Nur77 transactivation in testicular Leydig cells. These findings may provide a molecular mechanism involved in the TGF-beta1-mediated repression of testicular steroidogenesis. PMID- 25140529 TI - A quantitative linguistic analysis of National Institutes of Health R01 application critiques from investigators at one institution. AB - PURPOSE: Career advancement in academic medicine often hinges on the ability to garner research funds. The National Institutes of Health's (NIH's) R01 award is the "gold standard" of an independent research program. Studies show inconsistencies in R01 reviewers' scoring and in award outcomes for certain applicant groups. Consistent with the NIH recommendation to examine potential bias in R01 peer review, the authors performed a text analysis of R01 reviewers' critiques. METHOD: The authors collected 454 critiques (262 from 91 unfunded and 192 from 67 funded applications) from 67 of 76 (88%) R01 investigators at the University of Wisconsin-Madison with initially unfunded applications subsequently funded between December 2007 and May 2009. To analyze critiques, the authors developed positive and negative grant application evaluation word categories and selected five existing categories relevant to grant review. They analyzed results with linear mixed-effects models for differences due to applicant and application characteristics. RESULTS: Critiques of funded applications contained more positive descriptors and superlatives and fewer negative evaluation words than critiques of unfunded applications. Experienced investigators' critiques contained more references to competence. Critiques showed differences due to applicant sex despite similar application scores or funding outcomes: more praise for applications from female investigators, greater reference to competence/ability for funded applications from female experienced investigators, and more negative evaluation words for applications from male investigators (all P<.05). CONCLUSIONS: Results suggest that text analysis is a promising tool for assessing consistency in R01 reviewers' judgments, and gender stereotypes may operate in R01 review. PMID- 25140530 TI - Refocusing medical education reform: beyond the how. AB - Integration of the basic and clinical sciences has been at the heart of medical education reform efforts for nearly a century. Neither the rate nor magnitude of actual progress suggests that reform is anywhere near completion, which presents a challenge to educators to seek ways to overcome significant obstacles to change. Robin Hopkins and colleagues, authors of the Perspective in this issue of Academic Medicine that has prompted this invited Commentary, are among those proposing interesting and useful answers to why integration has not been better achieved. This Commentary affirms the importance of finding better ways to accomplish curricular reform, while contending that real curricular reform must move well beyond the integration of basic and clinical sciences. Drawing from the 2014 report of the Robert Wood Johnson Foundation's Commission to Build a Healthier America, the authors cite evidence of significant disparities and growing health challenges facing Americans today. They discuss three key recommendations from the report: attending to early childhood experiences, providing healthy choices within communities, and, particularly, rethinking the education of health professionals. Next, the authors detail the implications of these recommendations for medical education, stressing both the urgency and importance of moving to adopt these as directions for real reform that will address today's health care challenges. PMID- 25140531 TI - Educating the educators: a key to curricular integration. AB - According to Hopkins and colleagues, integration of basic science and clinical practice in the medical curriculum has been "incremental" at best, rather than transformative, in part because of a lack of focus on the individuals central to the integration--basic science educators. These authors maintain that those who lead change in education should not only address the systemic structure but also understand the meaning of integration for individual basic scientists at different levels of change. Their view has merit, and this Commentary author suggests three concrete steps that institutions should undertake to engage basic scientists who are interested in becoming "educationally literate" and assuming leadership roles in curriculum integration: (1) Offer opportunities to help interested basic science teaching faculty gain the necessary expertise to become skilled educators; (2) establish institutional programs and structures that foster a community of medical educators across departments and schools; and (3) align institutional priorities and incentives to promote, rather than hinder, integration in medical education. In essence, curricular integration cannot succeed if the participants do not understand the "language of education." Furthermore, faculty who opt for an education-focused career path should be brought together from across departments, centers, and schools to create a community of educators within the academic health center. Finally, institutional leaders should place high value and proper incentives in terms of recognition and opportunities for faculty advancement to ensure that those opting to gain additional training as skilled educators will drive innovation and help move curricular reform from incremental change to transformation. PMID- 25140532 TI - An efficient approach for differentiating Alzheimer's disease from normal elderly based on multicenter MRI using gray-level invariant features. AB - Machine learning techniques, along with imaging markers extracted from structural magnetic resonance images, have been shown to increase the accuracy to differentiate patients with Alzheimer's disease (AD) from normal elderly controls. Several forms of anatomical features, such as cortical volume, shape, and thickness, have demonstrated discriminative capability. These approaches rely on accurate non-linear image transformation, which could invite several nuisance factors, such as dependency on transformation parameters and the degree of anatomical abnormality, and an unpredictable influence of residual registration errors. In this study, we tested a simple method to extract disease-related anatomical features, which is suitable for initial stratification of the heterogeneous patient populations often encountered in clinical data. The method employed gray-level invariant features, which were extracted from linearly transformed images, to characterize AD-specific anatomical features. The intensity information from a disease-specific spatial masking, which was linearly registered to each patient, was used to capture the anatomical features. We implemented a two-step feature selection for anatomic recognition. First, a statistic-based feature selection was implemented to extract AD-related anatomical features while excluding non-significant features. Then, seven knowledge-based ROIs were used to capture the local discriminative powers of selected voxels within areas that were sensitive to AD or mild cognitive impairment (MCI). The discriminative capability of the proposed feature was measured by its performance in differentiating AD or MCI from normal elderly controls (NC) using a support vector machine. The statistic-based feature selection, together with the knowledge-based masks, provided a promising solution for capturing anatomical features of the brain efficiently. For the analysis of clinical populations, which are inherently heterogeneous, this approach could stratify the large amount of data rapidly and could be combined with more detailed subsequent analyses based on non-linear transformation. PMID- 25140534 TI - Cationic poly(amidoamine) dendrimers induced cyto-protective autophagy in hepatocellular carcinoma cells. AB - Poly(amidoamine) (PAMAM) dendrimers are proposed as one of the most promising nanomaterials for biomedical applications because of their unique tree-like structure, monodispersity and tunable properties. In this study, we found that PAMAM dendrimers could induce the formation of autophagosomes and the conversion of microtubule-associated protein 1 light chain 3 (LC3) in hepatocellular carcinoma HepG2 cells, while the inhibition of the Akt/mTOR and activation of the Erk 1/2 signaling pathways were involved in autophagy-induced by PAMAM dendrimers. We also investigated the suppression of autophagy with the obviously enhanced cytotoxicity of PAMAM dendrimers. Moreover, the blockage of a reactive oxygen species (ROS) could enhance the growth inhibition and apoptosis of hepatocellular carcinoma cells, induced by PAMAM dendrimers through reducing autophagic effects. Taken together, these findings explored the role and mechanism of autophagy induced by PAMAM dendrimers in HepG2 cells, provided new insight into the effect of autophagy on drug delivery nanomaterials and tumor cells and contributed to the use of a drug delivery vehicle for hepatocellular carcinoma treatment. PMID- 25140535 TI - Oral delivery mediated RNA interference of a carboxylesterase gene results in reduced resistance to organophosphorus insecticides in the cotton Aphid, Aphis gossypii Glover. AB - BACKGROUND: RNA interference (RNAi) is an effective tool to examine the function of individual genes. Carboxylesterases (CarE, EC 3.1.1.1) are known to play significant roles in the metabolism of xenobiotic compounds in many insect species. Previous studies in our laboratory found that CarE expression was up regulated in Aphis gossypii (Glover) (Hemiptera: Aphididae) adults of both omethoate and malathion resistant strains, indicating the potential involvement of CarE in organophosphorus (OP) insecticide resistance. Functional analysis (RNAi) is therefore warranted to investigate the role of CarE in A. gossypii to OPs resistance. RESULT: CarE expression in omethoate resistant individuals of Aphis gossypii was dramatically suppressed following ingestion of dsRNA-CarE. The highest knockdown efficiency (33%) was observed at 72 h after feeding when dsRNA CarE concentration was 100 ng/uL. The CarE activities from the CarE knockdown aphids were consistent with the correspondingly significant reduction in CarE expression. The CarE activity in the individuals of control aphids was concentrated in the range of 650-900 mOD/per/min, while in the individuals of dsRNA-CarE-fed aphids, the CarE activity was concentrated in the range of 500-800 mOD/per/min. In vitro inhibition experiments also demonstrated that total CarE activity in the CarE knockdown aphids decreased significantly as compared to control aphids. Bioassay results of aphids fed dsRNA-CarE indicated that suppression of CarE expression increased susceptibility to omethoate in individuals of the resistant aphid strains. CONCLUSION: The results of this study not only suggest that ingestion of dsRNA through artificial diet could be exploited for functional genomic studies in cotton aphids, but also indicate that CarE can be considered as a major target of organophosphorus insecticide (OPs) resistance in A. gossypii. Further, our results suggest that the CarE would be a propitious target for OPs resistant aphid control, and insect-resistant transgenic plants may be obtained through plant RNAi-mediated silencing of insect CarE expression. PMID- 25140536 TI - The influence of pressure on the intrinsic dissolution rate of amorphous indomethacin. AB - New drug candidates increasingly tend to be poorly water soluble. One approach to increase their solubility is to convert the crystalline form of a drug into the amorphous form. Intrinsic dissolution testing is an efficient standard method to determine the intrinsic dissolution rate (IDR) of a drug and to test the potential dissolution advantage of the amorphous form. However, neither the United States Pharmacopeia (USP) nor the European Pharmacopeia (Ph.Eur) state specific limitations for the compression pressure in order to obtain compacts for the IDR determination. In this study, the influence of different compression pressures on the IDR was determined from powder compacts of amorphous (ball milling) indomethacin (IND), a glass solution of IND and poly(vinylpyrrolidone) (PVP) and crystalline IND. Solid state properties were analyzed with X-ray powder diffraction (XRPD) and the final compacts were visually observed to study the effects of compaction pressure on their surface properties. It was found that there is no significant correlation between IDR and compression pressure for crystalline IND and IND-PVP. This was in line with the observation of similar surface properties of the compacts. However, compression pressure had an impact on the IDR of pure amorphous IND compacts. Above a critical compression pressure, amorphous particles sintered to form a single compact with dissolution properties similar to quench-cooled disc and crystalline IND compacts. In such a case, the apparent dissolution advantage of the amorphous form might be underestimated. It is thus suggested that for a reasonable interpretation of the IDR, surface properties of the different analyzed samples should be investigated and for amorphous samples the IDR should be measured also as a function of the compression pressure used to prepare the solid sample for IDR testing. PMID- 25140533 TI - Quantifying the role of adverse events in the mortality difference between first and second-generation antipsychotics in older adults: systematic review and meta synthesis. AB - BACKGROUND: Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture. OBJECTIVES: 1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs. DATA SOURCES: Pubmed and Science Citation Index. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a "new user" design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events. STUDY APPRAISAL AND SYNTHESIS METHODS: For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference-comparing FGAs to SGAs mediated by their difference in risk for the medical event. RESULTS: We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference. CONCLUSIONS: The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs. PMID- 25140537 TI - "Push-Through" Rod Passage Technique for the Improvement of Lumbar Lordosis and Sagittal Balance in Minimally Invasive Adult Degenerative Scoliosis Surgery. AB - OF BACKGROUND DATA: Traditional open surgical techniques for correction of adult degenerative scoliosis (ADS) are often associated with increased blood loss, postoperative pain, and complications. Minimally invasive (MIS) techniques have been utilized to address these issues; however, concerns regarding improving certain alignment parameters have been raised. OBJECTIVE: A new "push-through" technique for MIS correction of ADS has been developed wherein a rod is bent before its placement into the screw heads and then contoured further to yield improved correction of radiographic parameters. METHODS AND STUDY DESIGN: Preoperative and postoperative radiographic measurements of 3 patients who underwent MIS correction of scoliosis using the "push-through" technique were compared with 22 prior patients who had received traditional MIS correction. All patients received staged correction of scoliosis. The first stage involved insertion of lateral lumbar interbodies. Standing x-rays were then evaluated for overall global balance. The second stage involved appropriate MIS facetectomies, facet fusions, posterior transforaminal interbodies at lower lumbar segments, and finally the placement of rods.TECHNIQUE OVERVIEW:: (1) A long rod composed of titanium is bent with a mild lordosis and passed through the extensions of the screw heads cephalad to caudad. (2) The rod is passed fully through the incision so it extrudes from the caudal end of the construct. At this point, further lordosis is bent into the rods. (3) The rod is then pulled back into the appropriate position. (4) The unnecessary cephalad rod is then cut to appropriate length with a circular saw. (5) Rod reducers are then sequentially lowered and tightened to achieve the desired correction. RESULTS: Mean age for all patients was 66.02 years. Preoperative coronal Cobb, sagittal vertical axis (SVA), and pelvic incidence (PI) were similar in all patients, whereas lumbar lordosis (LL) was smaller (15.27 vs. 29.85 degrees, P=0.00389) and pelvic tilt (PT) was larger (37.00 vs. 27.00 degrees, P=0.00011) in "push-through" patients. Postoperatively, "pushthrough" patients experienced greater correction of LL (21.93 vs. 3.70 degrees, P=0.00001), PI-LL (-18.57 vs. -0.26 degrees, P=0.00471), PT (-7.67 vs. 0.40 degrees, P=0.00341), SVA (-40.67 mm vs. 0.95 mm, P=0.05846), and coronal Cobb (-20.23 vs. -18.76 degrees, P=0.75). CONCLUSIONS: This new method of contouring a rod enables improved LL. This technique is easy to perform and can be a valuable tool in treating ADS using MIS techniques. PMID- 25140538 TI - Bioreactor droplets from liposome-stabilized all-aqueous emulsions. AB - Artificial bioreactors are desirable for in vitro biochemical studies and as protocells. A key challenge is maintaining a favourable internal environment while allowing substrate entry and product departure. We show that semipermeable, size-controlled bioreactors with aqueous, macromolecularly crowded interiors can be assembled by liposome stabilization of an all-aqueous emulsion. Dextran-rich aqueous droplets are dispersed in a continuous polyethylene glycol (PEG)-rich aqueous phase, with coalescence inhibited by adsorbed ~130-nm diameter liposomes. Fluorescence recovery after photobleaching and dynamic light scattering data indicate that the liposomes, which are PEGylated and negatively charged, remain intact at the interface for extended time. Inter-droplet repulsion provides electrostatic stabilization of the emulsion, with droplet coalescence prevented even for submonolayer interfacial coatings. RNA and DNA can enter and exit aqueous droplets by diffusion, with final concentrations dictated by partitioning. The capacity to serve as microscale bioreactors is established by demonstrating a ribozyme cleavage reaction within the liposome-coated droplets. PMID- 25140539 TI - Detection of a right carotid focus of 18F-FDG predicted an ischemic stroke. AB - A 60-year-old woman was referred into our department for staging of an endometrial carcinoma. In addition to peritoneal and nodes metastases, F-FDG PET/CT showed a calcified plaque of the right carotid with focal uptake. One month later, the patient presented left hemiparesis, suggesting a right hemisphere stroke. MRI confirmed frontal infarction in the anterior cerebral artery territory. F-FDG is suggested to be a valuable tool to detect vessel wall inflammation; detection of focal arterial uptake on PET/CT suggests unstable plaque and requires urgent patient's management to prevent vascular events in a population already weakened by both disease and therapy. PMID- 25140540 TI - CyberKnife radiosurgery planning of a secreting pituitary adenoma performed with 68Ga DOTATATE PET and MRI. AB - The images of a patient with acromegaly, who previously underwent operation for pituitary adenoma, were obtained. The MRI scan showed a mass in the right cavernous sinus, with biochemical test results positive for the presence of a hormonally active adenoma. The patient was scheduled for CyberKnife radiotherapy. Radiotherapy planning was carried out using MRI and PET/CT scan with somatostatin analog 68Ga DOTATATE. The latter showed radiopharmaceutical uptake on the adenomatous residual mass. Contours were drawn on MRI and PET images and were summed up to devise the radiotherapy plan. The patient was treated with a total dose of 24 Gy. PMID- 25140541 TI - 18F-FDG PET/CT in anti-LGI1 encephalitis: initial and follow-up findings. AB - Anti-LGI1 encephalitis is a subgroup of autoimmune encephalitis, characterized by memory impairments, seizures, and behavioral problems. The diagnosis can be made by clinical manifestation with a help of serum autoantibody test. There was lack of imaging studies to evaluate and monitor the disease activity by anatomical and functional information. Here, we report serial F-FDG PET/CT findings in a patient with anti-LGI1 encephalitis. Intense F-FDG uptake was initially noted in bilateral limbic system at active disease status, and then decreased and eventually normalized according to the clinical improvement after treatment. F FDG PET/CT can be used to evaluate treatment response of encephalitis. PMID- 25140543 TI - 18F-FDG PET/CT demonstrating primary bone lymphoma of the extremities mimicking an inflammatory peripheral arthropathy. AB - A 66-year-old woman presents with progressive bilateral swelling of her fingers, elbows, and toes. Initially thought to represent an inflammatory peripheral arthropathy, the patient underwent rheumatology review, but subsequent tissue biopsy confirmed diffuse large B-cell lymphoma. Results of bone marrow biopsy and staging CT were negative. F-FDG PET/CT demonstrates FDG-avid bony and adjacent soft tissue disease limited to the extremities with an excellent metabolic response to primary chemotherapy. This is a rare case of primary bone lymphoma limited to the extremities mimicking an inflammatory peripheral arthropathy. PMID- 25140542 TI - CT, MRI, and 18F-FDG PET/CT in a patient with nested stromal epithelial tumor of the liver. AB - An 11-year-old girl presented with abnormal weight gain and was found to have hepatomegaly. MRI of the abdomen revealed a 20-cm hepatic mass. F-FDG PET/CT showed a large hypermetabolic calcified hepatic mass and couple of mildly hypermetabolic pulmonary nodules with associated intrathoracic lymphadenopathy. Liver biopsy was consistent with nested stromal epithelial tumor of the liver, a rare nonhepatocytic, nonbiliary primary neoplasm of the liver associated with variable calcification and ossification. PMID- 25140544 TI - Accidental cannulation of a femoral central venous catheter into the iliolumbar vein: incidental detection by bone scintigraphy. AB - Central venous catheterization at the femoral site is associated with higher complication rates of infections and thrombosis than at the jugular or subclavian sites. However, the procedure of insertion at the femoral site is considered safer. We present a unique but dangerous positioning of a left femoral central venous catheter into the iliolumbar vein. We were aware of this accidental cannulation by chance when our patient underwent bone scintigraphy. Although a few cases were reported about accidental cannulation into the ascending lumbar vein, this is the first case where a femoral central venous catheter was misplaced into the iliolumbar vein. PMID- 25140545 TI - Metastatic undifferentiated spindle cell sarcoma of the thyroid gland evaluated by 18F-FDG PET/CT. AB - We describe a rare case of metastatic undifferentiated spindle cell sarcoma (USCS) of the thyroid gland evaluated by 18F-FDG PET/CT. A 63-year-old male patient with histological diagnosis of USCS of the thyroid gland underwent 18F FDG PET/CT for staging. PET/CT revealed increased radiopharmaceutical uptake corresponding to a thyroid mass and mild 18F-FDG uptake in a 7-mm lung nodule, which was diagnosed as USCS metastasis. Based on these findings, the patient was referred to surgery and chemotherapy, but he died 6 months later for disease progression. PMID- 25140546 TI - FDG PET/CT in evaluation of unusual cutaneous manifestations of breast cancer. AB - Cutaneous metastases of primary internal malignancies are rare, with an incidence of 0.7% to 10.4%. Cutaneous manifestations due to breast cancer are the most common metastases dermatologists observe, with a prevalence of 2.4% and an incidence of 23.9%. Presence of cutaneous metastases is usually a late event in disease progression, indicating grave prognosis. Recognition of cutaneous breast cancer metastases significantly alters therapeutic plans, especially when the disease was thought to be successfully cured. F-FDG PET CT imaging can detect cutaneous metastasis and sites of distant metastases and monitor response to therapy. We report 3 patients with cutaneous-predominant breast carcinoma seen by FDG PET/CT. PMID- 25140547 TI - 18F-FDG PET/CT in a case of parasite infection mimicking lung and breast malignancy. AB - A 51-year-old woman with dyspnea on exertion, fever, pleural effusion, and pericardial thickening underwent F-FDG PET/CT, which revealed focal hypermetabolic lesions in the right lung and left breast. The histopathology of the lesions was compatible with infiltration of inflammatory cells. Blood eosinophil counts were elevated, and enzyme-linked immunoassays were positive for antibodies to several parasites. After antiparasite medication, blood eosinophil counts were normalized, and PET/CT demonstrated complete disappearance of abnormal FDG accumulation in the lung and breast. PMID- 25140548 TI - Focal increased 18F FP-CIT uptake in a recent ischemic lesion in the frontal lobe. AB - A 65-year-old male patient was referred for rapid functional decline over 1 month with dysphagia and dysarthria. Past history disclosed left side weakness for 5 years. F FP-CIT PET/CT was performed to evaluate the possibility of pseudobulbar palsy. Images showed a defect in the right posterior putamen that was consistent with an old cerebral infarction lesion. Unexpectedly, an oval area of intense F FP-CIT uptake was found in the left frontal lobe. MRI and F-FDG PET/CT indicated the lesion to be caused by recent cerebral ischemia. PMID- 25140549 TI - Detecting interval metastases and response assessment using 18F-FDG PET/CT after neoadjuvant chemoradiotherapy for esophageal cancer. AB - AIM: The aim of this study is to evaluate the potential of FDG PET/CT for the detection of interval distant metastases after neoadjuvant chemoradiotherapy (CRT) and the prediction of the pathologic response to CRT in esophageal cancer patients. PATIENTS AND METHODS: In this retrospective study, all esophageal cancer patients for whom CRT followed by surgery was planned between January 2008 and April 2013 and in whom an FDG PET/CT was performed before and after CRT were included. For the response analyses, both FDG PET/CT scans had to be made on a similar scanner. Metabolic response of the primary tumor was assessed using the SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). These parameters were correlated with the pathologic response using the tumor regression grade (TRG) scale according to Mandard et al (Cancer. 1994;73:2680 2686). RESULTS: In 6 (8%) of 76 consecutively treated patients, new distant metastases were detected on FDG PET/CT after neoadjuvant CRT; these patients therefore did not undergo operation. Forty-eight (63%) of 76 patients were eligible for response analysis. The relative change in SUVmax, MTV, and TLG was significantly different between patients with a major (TRG, 1-2) and a minor response (TRG, 3-5) but not between patients with and without a pathologic complete response. The area under the curve of the receiver operating characteristic for predicting a major response was 0.70 (95% confidence interval, 0.65-0.92) for a relative decrease in SUVmax, compared with 0.73 (95% confidence interval, 0.58-0.88) both for MTV and TLG. A relative decrease in SUVmax of 60% or more had the highest positive predictive value (75%). CONCLUSIONS: Futile surgery was prevented in 8% of our esophageal cancer patients because interval metastases were detected on an FDG PET/CT after neoadjuvant CRT. The accuracy for predicting a complete or major pathologic response was limited and does not support the use of FDG PET/CT for refraining from surgical treatment. PMID- 25140550 TI - 18F-FDG PET/CT finding of bilateral primary breast mucosa-associated lymphoid tissue lymphoma. AB - Primary breast lymphoma is an extremely rare disease. Primary breast mucosa associated lymphoid tissue (MALT) lymphoma is even rarer, and bilateral involvement is exceptional. We report on the F-FDG PET/CT findings in a patient with primary bilateral breast MALT lymphoma. F-FDG PET/CT showed hypermetabolic masses in both breasts. The patient was confirmed with bilateral primary breast MALT lymphoma after total mastectomy. Despite its rarity, primary breast MALT lymphoma should be considered in patients with hypermetabolic masses in the breast. If primary breast MALT lymphoma is suspected, F-FDG PET/CT is a useful tool for initial staging in patients. PMID- 25140551 TI - Radioiodine uptake in an ovarian mature teratoma detected with SPECT/CT. AB - A 28-year-old woman underwent a near-total thyroidectomy for papillary carcinoma. Before radioiodine therapy, the serum thyroid-stimulating hormone level was 50 MUIU/mL, the thyroglobulin level was 1 MUg/L, and the antithyroglobulin was negative. She received 100 mCi of I for ablation of residual thyroid tissue. After therapy, I whole-body scan demonstrated focal uptake in the right pelvic area, which localized to the right ovary on SPECT/CT fusion images. The ovarian cyst was resected, and histopathological examination revealed a mature teratoma without thyroid tissue component. At 6-month follow-up, the whole-body radioiodine scan was normal, and serum thyroglobulin was undetectable. PMID- 25140552 TI - Whole-body 18F-fluorocholine (FCH) PET/CT and MRI of the spine for monitoring patients with castration-resistant prostate cancer metastatic to bone: a pilot study. AB - INTRODUCTION: Several treatments are proposed for castration-resistant prostate cancer (CRPC) at the metastatic stage. Monitoring of response using serum prostate-specific antigen (PSA) levels (sPSA) can be insufficient at this stage. Imaging has been proposed, in particular, nuclear medicine functional imaging and MRI, since response of predominant bone metastases is hardly evaluable on CT. Our aim was to evaluate in patients with CRPC with bone metastases, before and after various treatment lines, the evolution of sPSA, whole-body 18F-fluorocholine (FCH) PET/CT and spine MRI (sMRI) that has been proposed for detection of imminent malignant spinal cord compression. PATIENTS AND METHODS: We retrospectively gathered a pilot series of 10 patients with CRPC metastatic to bone who had 47 PSA assays, FCH PET/CT, and spine-MRI (sMRI) performed concomitantly as routine examinations, before the beginning and at the end of 37 therapeutic intervals (TIs). Blinded reading of FCH PET/CT and sMRI was performed to evaluate visually whether or not the disease has been progressing (new lesions, greater size, or greater uptake intensity of known lesions) between the initial and the final examination of each TI. RESULTS: Visual interpretations limited to spine FCH (sFCH) PET/CT and sMRI were in accordance for 34 TIs (92%): 14 progressions and 20 nonprogressions. In 2 cases, sFCH did not detect lesions visible on sMRI: one epiduritis and one 6-mm lesion. In 1 case, MRI missed a lesion in the sacrum that was detected on sFCH. When whole-body FCH (wbFCH) PET/CT was taken into account, the agreement with sMRI was limited to 29 TIs (78%). The 8 discrepant cases were all wbFCH positive and sMRI negative, that is, a significantly higher frequency of positivity for wbFCH (P < 0.008). Serum PSA levels increased by more than 25% during 21 TIs, whereas no progression was visible in 8 TIs on sMRI and in 2 TIs on wbFCH. In 5 TIs, sPSA decreased by more than 50%, and progression was never detected on imaging. CONCLUSION: In detecting progression in patients with CRPC metastatic to bone, results of spine imaging with sMRI and sFCH PET/CT were highly correlated, whereas wbFCH PET/CT showed significantly more progression statues comparing to sMRI alone related to the exploration of other parts of the skeleton and of soft tissue. PMID- 25140553 TI - Clear cell adenocarcinoma of the urethra: 18F-FDG PET/CT imaging. AB - Clear cell adenocarcinoma of the urethra is a rare and aggressive tumor of female gender preponderance. This neoplasm, the origin of which is still widely debated, has been reported with CT and MRI in case reports and small series. To the previously published conventional cross-sectional imaging description, the authors add the PET/CT features of this uncommon urologic neoplasm at its advanced stage in a 60-year-old patient complaining of urinary retention. PMID- 25140554 TI - A gluten-free vegan meal for gastric emptying scintigraphy: establishment of reference values and its utilization in the evaluation of diabetic gastroparesis. AB - PURPOSE: The aim of this study was to describe the preparation of radiolabeled idli (savory cake) meal for use as an alternate to the egg white sandwich (EWS) meal in gastric emptying scintigraphy (GES). Furthermore, the aim of this study was to establish normal emptying rates for this meal and present our experience in using it in the evaluation of diabetic gastroparesis. PATIENTS AND METHODS: The meal was prepared using a universally available packaged mix labeled with 1 mCi 99mTc sulfur colloid, and the stability of labeling was tested up to 4 hours in simulated gastric fluid. One hundred thirteen healthy volunteers (aged 20-78 years; 54 women, 59 men) underwent GES study using the idli meal. Gastric retention at one-half, 1, 2, and 4 hours after ingestion of the meal was estimated, and the normal limits were set using the fifth and 95th percentile values at each period. Having established its normal emptying rates, the idli meal was further used to evaluate 70 patients suspected with diabetic gastroparesis. RESULTS: The idli meal, with a calorific value ~282 kcal, has a relatively higher fat content (8% of total mass) than EWS. More than 96% of 99mTc sulfur colloid remained bound to the meal after 4 hours suspension in simulated gastric fluid. Gastric retention greater than 30% and greater than 6% at 2 hours and 4 hours, respectively, indicated delayed gastric emptying, whereas retention less than 30% at 1 hour suggested rapid emptying. Among patients suspected with diabetic gastroparesis, delayed gastric emptying was identified in 76%, and rapid emptying was seen in 4.2%. CONCLUSIONS: Radiolabeled idli meal is a good alternative to EWS meal for routine GES, especially among patients with specific dietary restrictions. PMID- 25140555 TI - Assessing tumor hypoxia in head and neck cancer by PET with 62Cu-diacetyl-bis(N4 methylthiosemicarbazone). AB - PURPOSE: The aim of this study was to investigate the potential of PET imaging with a hypoxia-selective tracer 62Cu-diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) for evaluating the prognosis of patients with head and neck cancer (HNC). METHODS: Twenty-five patients with HNC including stage II to IV underwent both 62Cu-ATSM and 18F-FDG PET before the initiation of treatment. Volumes of interest were placed on the tumor and sternocleidomastoid muscles to obtain SUVmax and to calculate the tumor-to-muscle activity ratio (TMR). The PET results were correlated with clinical follow-up, and the receiver operating characteristic analysis was used to determine the optimal cutoff values. Progression-free survival (PFS) and cause-specific survival (CSS) were statistically analyzed. RESULTS: Patients were followed up for periods ranging from 4 to 32 months. Twelve patients died from local recurrence or metastasis of a primary cancer, and 2 had recurrence of the 13 remaining patients. Mean (SD) periods of PFS and CSS were 15.5 (12.5) and 18.6 (11.0) months, respectively. Optimal cutoff values for each PET index were as follows: SUVs of 62Cu-ATSM (SUVATSM) and FDG were 3.6 and 7.9; TMRs of ATSM (TMRATSM) and FDG were 3.2 and 5.6. When the cutoff for TMRATSM was set at 3.2, patients with a greater TMRATSM had significantly worse PFS (P = 0.014) and CSS (P = 0.031). Two-year PFS and CSS rates were 73% and 80% for patients with a lower TMRATSM (<=3.2); however, they were 20% and 33% for those with hypoxic tumors (TMRATSM, >3.2), respectively. F FDG-related indices did not show any significant difference in either PFS or CSS. CONCLUSIONS: Pretreatment 62Cu-ATSM PET is useful for predicting the prognosis of patients with HNC. PMID- 25140556 TI - Nodular fasciitis mimicking soft tissue metastasis on 18F-FDG PET/CT during surveillance. AB - Nodular fasciitis (NF) is a common benign soft tissue tumor. However, F-FDG PET/CT findings of NF are limited. Two cases of NF are described that mimic soft tissue metastasis on F-FDG PET/CT during surveillance. F-FDG PET/CT is well documented in the surveillance of malignancy and increasing worldwide. There are growing chances of encountering FDG-avid nonmalignant soft tissue lesion. Nodular fasciitis could be considered as possible diagnosis on F-FDG PET/CT if a solitary well- circumscribed ovoid hypermetabolic soft tissue lesion is located in a muscle, intermuscular space, or adjacent tendon, especially in patients with a clinically low probability of tumor recurrence or metastasis. PMID- 25140557 TI - Detection of osseous metastasis by 18F-NaF/18F-FDG PET/CT versus CT alone. AB - PURPOSE: Sodium fluoride PET (18F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered 18F-NaF and 18F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer 18F-NaF18/F-FDG PET/CT with CT alone for detection of osseous metastasis. PATIENTS AND METHODS: Seventy-five participants with biopsy-proven malignancy were consecutively enrolled from a single center and underwent combined 18F-NaF/18F-FDG PET/CT and diagnostic CT scans. PET/CT as well as CT only images were reviewed in blinded fashion and compared with the results of clinical, imaging, or histological follow-up as a truth standard. RESULTS: Sensitivity of the combined 18F-NaF/18F-FDG PET/CT was higher than that of CT alone (97.4% vs 66.7%). CT and 18F-NaF/18F-FDG PET/CT were concordant in 73% of studies. Of 20 discordant cases, 18F-NaF/18F-FDG PET/CT was correct in 19 (95%). Three cases were interpreted concordantly but incorrectly, and all 3 were false positives. A single case of osseous metastasis was detected by CT alone, but not by 18F-NaF/18F-FDG PET/CT. CONCLUSIONS: Combined 18F-NaF/18F-FDG PET/CT outperforms CT alone and is highly sensitive and specific for detection of osseous metastases. The concordantly interpreted false-positive cases demonstrate the difficulty of distinguishing degenerative from malignant disease, whereas the single case of metastasis seen on CT but not PET highlights the need for careful review of CT images in multimodality studies. PMID- 25140558 TI - 131I abnormal uptake by the thyroid bed from Zuckerkandl tubercle diagnosis by 131I SPECT/CT. AB - After thyroid remnant ablation following total thyroidectomy for thyroid cancer, 131I SPECT/CT revealed 131I uptake, regarded as thyroid bed uptake on planar images, in the anterior cervical region. On SPECT/CT, the 131I uptake focus appeared at the esophagus, suggesting esophageal invasion. No esophageal invasion had been recognized intraoperatively, and no residual uptake was detected by 131I scintigraphy evaluating therapeutic effects 3 months after ablation. Preoperative CT revealed a retrotracheal space portion extending from the normal thyroid with the same density, suggesting Zuckerkandl tubercle. Abnormal uptake on SPECT/CT was deemed Zuckerkandl tubercle-derived thyroid bed uptake. PMID- 25140559 TI - Sister Mary Joseph Nodules on 99mTc HYNIC-TOC scintigraphy in patients with neuroendocrine tumors. AB - A Sister Mary Joseph nodule represents an umbilical metastasis, which is more commonly caused by a primary malignancy in gastrointestinal tract or from reproductive system. We report Sister Mary Joseph nodules caused by neuroendocrine tumor and revealed on Tc HYNIC-TOC scintigraphy. PMID- 25140560 TI - Role of semiquantitative assessment of regional binding potential in 123I-FP-CIT SPECT for the differentiation of frontotemporal dementia, dementia with Lewy bodies, and Alzheimer's dementia. AB - INTRODUCTION: I-FP-CIT SPECT is increasingly used to differentiate between Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB). The role of I-FP CIT SPECT in frontotemporal dementia (FTD) is rather unclear, albeit nigrostriatal involvement may occur. The aim of this study was to evaluate its role in the differentiation of FTD, DLB, and AD. METHODS: We analyzed 34 patients with clinical diagnosis of FTD (n = 13), DLB (n = 12), and AD (n = 9) undergoing combined F-FDG PET and I-FP-CIT SPECT. We performed a semiquantitative region of interest-based analysis to determine the binding potential values in caudate nucleus, putamen, and whole striatum including the caudate/putamen binding potential ratio and asymmetry indices. The receiver operating characteristic analyses and multinomial logistic regression were conducted to assess discrimination accuracy. RESULTS: The putaminal binding potential separated DLB from AD with high accuracy (area under the receiver operating characteristic curve [AUC], 0.94). It also discriminated FTD from DLB with high accuracy (AUC, 0.92), whereas differentiation between FTD and AD was less accurate (AUC, 0.74). The binding potential ratio also provided high accuracy for differentiation of FTD and DLB (AUC, 0.91). Combination of these 2 parameters yielded slightly higher results for differentiation of FTD and DLB (AUC, 0.97). In a group including all patients, accuracy remained very high for DLB (AUC, 0.95), whereas values for FTD (AUC, 0.81) and AD (AUC, 0.80) were lower. CONCLUSIONS: Semiquantitative assessment of striatal dopamine transporter availability can differentiate between FTD and DLB as well as DLB and AD with high accuracy, whereas discrimination between AD and FTD is limited. PMID- 25140561 TI - Quantitative measurement of blood flow volume in the major intracranial arteries by using 123i-iodoamphetamine SPECT. AB - PURPOSE: The aim of this study was to establish the novel automatic method to quantify blood flow volumes of the major intracranial arteries by using SPECT. METHODS: We created the vascular templates to cover the territory supplied by the major intracranial arteries. Each blood flow volume was calculated as the regional cerebral blood flow on SPECT using this template * volume size of the template. In this study, we evaluated the volume flows in 22 cerebral hemispheres with normal perfusion and 28 hemispheres with severe stenosis in the internal cerebral artery (ICA) or middle cerebral artery (MCA) and that at acetazolamide test in 16 normal hemispheres and 20 hemispheres with stenosis. RESULTS: The mean blood flow volumes of the ICA and MCA in the normal hemispheres increased to more than 40% after acetazolamide test (161-228 mL/min for ICA and 111-157 mL/min for MCA), although those in the hemispheres with stenosis increased to less than 35% (158-192 mL/min for ICA and 107-127 mL/min for MCA). The receiver operating characteristic analyses revealed that the simple difference between the blood flow volume at acetazolamide test and that at rest using the new MCA template was superior to detecting reduction of cerebrovascular reactivity (CVR), compared with the conventional percent CVR using the original template. CONCLUSIONS: Blood flow volumes of the intracranial arteries had been able to be quantified automatically on SPECT, and difference of CVR was available for predicting the blood demand-supply balance. PMID- 25140562 TI - Clinical benefit of 11C methionine PET imaging as a planning modality for radiosurgery of previously irradiated recurrent brain metastases. AB - OBJECT: Stereotactic radiosurgery with gamma knife (GK-SRS) generally improves the focal control of brain metastases. Yet in cases of focal recurrence at a previous radiation site, MRI is often imperfect in differentiating between active tumor and radiation injury. We have examined whether the use of C methionine (MET) with PET will facilitate this differentiation and improve the outcome of GK SRS for focally recurrent brain metastases after prior treatment. METHODS: Eighty eight patients underwent GK-SRS for postirradiation recurrent brain metastases. Thirty-four patients received radiation in areas manifesting high MET uptake (PET group) in a dose-planning procedure using MET-PET/MRI fusion images. Fifty-four patients referred from other institutes received radiation based on dose planning information obtained from MRI (MRI group). RESULTS: Sex, age, and the ratio of breast cancer differed significantly between the MRI and PET groups. The total irradiation volume was significantly smaller in the PET group, and the minimal irradiation dose was significantly higher. In a multivariable statistical analysis, the use of MET-PET (P = 0.02) was independently associated with prolonged overall survival after treatment, Karnofsky performance status (P = 0.002), the number of lesions (P = 0.03), and patient's sex (P = 0.02). The median survival time was significantly longer in the PET group (18.1 months) than in the MRI group (8.6 months) (P = 0.01). CONCLUSION: 11C methionine-PET/MRI fusion images for dose planning lengthened survival in patients undergoing GK-SRS for focally recurrent brain metastases. PMID- 25140563 TI - PET response criteria for solid tumors predict survival at three months after intra-arterial resin-based 90Yttrium radioembolization therapy for unresectable intrahepatic cholangiocarcinoma. AB - PURPOSE: PET Response Criteria for Solid Tumors (PERCIST) were assessed and correlated with survival analysis after resin-based 90Yttrium (90Y) radioembolization therapy for intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: Target and overall PERCIST and Response Criteria for Solid Tumors (RECIST) treatment responses were assessed in consecutive patients treated with Y radioembolization for ICC refractory to standard chemotherapy. Significant measurable tumor was defined as 1 cm or greater in diameter and SUVpeak of 2.5 or greater in targeted and nontargeted lesions. The PERCIST defines complete response as resolution of 18F-FDG uptake within measurable lesions, and partial response as 30% reduction in 18F-FDG peak standardized uptake value in measurable lesions. Objective response included partial response and complete response. Survival analysis by Kaplan-Meier and log-rank proportional models was performed using SPSS software version 20.0 (IBM, Armonk, NY), and significance was set at P < 0.05. RESULTS: Median overall survival (OS) of 9 consecutive patients (56% women; mean age, 58 years) from 90Y therapy was 21.7 months. At 3 months, PERCIST objective response rate of target lesions was 77.7%, and target objective response on PERCIST correlated significantly to prolonged OS (P = 0.022). Overall objective PERCIST response at 3 months had significant correlation with OS (P = 0.011). Probability of death was significantly higher in overall nonresponders by PERCIST (hazard ratio, 12.3). No objective response was seen with RECIST. CONCLUSIONS: In patients with unresectable ICC refractory to standard chemotherapy, PERCIST at 3 months for assessment of imaging response after 90Y radioembolization therapy predict OS. PMID- 25140564 TI - Stratified radiotracer activity in a floppy neobladder on both 18F-FDG PET/CT and 99mTc-MDP bone scan. AB - 18F-FDG and 99mTc-MDP are excreted through the renal system. For the most part, radiotracers are uniformly distributed in the bladder; however, their distribution can exhibit unique patterns in certain situations. We present a case of stratified urine activity in a floppy neobladder on nuclear medicine imaging performed just after CT and MRI contrast studies, respectively. PMID- 25140565 TI - 11C-PiB PET/CT in nasopharyngeal amyloidosis associated with multiple myeloma. AB - We present an unusual case of nasopharyngeal amyloidosis associated with multiple myeloma. A 63-year-old woman presented with 2 months' history of epistaxis and dentalgia 3 years after being diagnosed with multiple myeloma. CT and C Pittsburgh compound B (PiB) PET images demonstrated that the intense C-PiB uptake corresponded to the nasal, paranasal, and palatal area matching the CT mass lesion. Histopathologic examination confirmed amyloidosis. PMID- 25140566 TI - Vesicocolic fistula detected by (99m)Tc-MAG3 renogram. AB - A 55-year-old man presented with 60-lb weight loss in 6 months. An abdominal CT demonstrated a large mass in the pelvis arising from the sigmoid colon and invading the urinary bladder. His elevated serum creatinine (1.25 mg/dL) triggered a request for a Tc-MAG3. Tc-MAG3 renogram demonstrated communication of the urinary bladder with the descending colon but no evidence of obstruction to drainage from the kidneys to the bladder. A retrograde cystogram confirmed a vesicocolic fistula. After multiple rounds of chemotherapy, the patient died 7 months later. PMID- 25140567 TI - [Until when will Brazil be known as the country of cesarean section?]. PMID- 25140568 TI - [Premature rupture of the membranes before the 35th week: perinatal outcomes]. AB - PURPOSE: To describe the perinatal outcomes after preterm premature rupture of membranes. METHODS: A retrospective cohort study was carried out at Instituto de Medicina Integral Prof. Fernando Figueira - IMIP from January 2008 to December 2012. A total of 124 preterm premature rupture of membranes singleton pregnancies, with gestational age <35, were included in the study. Pregnant women carrying fetuses with malformations, hypertensive syndromes, diabetes, or diagnosis of infections at admission were excluded. The pregnant women were hospitalized for conservative treatment with corticosteroids, antibiotics and tocolysis with nifedipine if necessary. The results are reported as frequency distributions and measures of central tendency and dispersion. RESULTS: Seventeen patients (13.7%) had a gestational age of less than 24 weeks. Mean maternal age was 25.7 years, mean gestational age at the diagnosis of preterm premature rupture of membranes was 29 weeks, mean amniotic fluid index was 3.5 cm, and mean latency period was 10.5 days. Most patients went into spontaneous labor by the 30th week of pregnancy, and the rate of vaginal delivery was 88.2%. Chorioamnionitis was the most frequent maternal complication (34.7%). Neonatal sepsis was observed in 12% of patients, and the perinatal mortality rate was 21.5% for the group at or beyond the 24th week of gestation and 76.5% for the group with less than 24 weeks of gestational age. CONCLUSIONS: A low maternal mortality rate was observed in preterm premature rupture of membranes; however, high rates of complications and perinatal death were observed, suggesting that other conduct protocols should be studied. PMID- 25140569 TI - [Neonatal mortality and avoidable causes in the micro regions of Sao Paulo state]. AB - PURPOSE: To identify spatial patterns of neonatal mortality distribution in the micro regions of Sao Paulo State and verify the role of avoidable causes in the composition of this health indicator. METHODS: This ecological exploratory study used neonatal mortality information obtained from Information System and Information Technology Department of the Brazilian National Healthcare System (DATASUS) in the period between the years 2007 and 2011. The digital set of micro regions of Sao Paulo State was obtained from Instituto Brasileiro de Geografia e Estatistica (IBGE). Moran Indexes were calculated for the neonatal mortality total rate and rate from avoidable causes; thematic maps were constructed with these rates, as well as the difference between them; and the Box Map was built. RESULTS: The overall neonatal mortality rate was 8.42/1,000 live births and neonatal mortality rate from avoidable causes of 6.19/1,000 live births. Moran coefficients (I) for these rates were significant (p-value<0.05) - for the total rate of neonatal mortality I=0.11 and for mortality from preventable causes I=0.19 -, and neonatal deaths were concentrated in southwest region and the Vale do Paraiba. If preventable causes were abolished, there would be a significant reduction in the average rate of overall neonatal mortality, from 8.42 to 2.23 deaths/1,000 live births, representing a decline of 73%. CONCLUSION: This study demonstrated that neonatal mortality rate would be close to the rates of developed countries if avoidable causes were abolished. PMID- 25140570 TI - Relationship between anxiety and overactive bladder syndrome in older women. AB - PURPOSE: The objective of this study was to investigate the relationship between overactive bladder syndrome and anxiety in older women. METHODS: Of the 198 older women who were invited, 29 were excluded and 166 were then divided into two groups according to the Advanced Questionnaire of Overactive Bladder (OAB-V8): one group with overactive bladder symptoms (OAB-V8>=8) and the other without the symptoms of an overactive bladder (OAB-V8<8). The purpose was to conduct a frequency analysis and to investigate the relation of the social demographic data and anxiety in the two groups. The Beck Anxiety Inventory (BAI) was used to evaluate the level of anxiety. The Kolmogorov-Smirnov test was used to determine the distribution of the data. The differences between the two groups for the continuous variables were analyzed by the Mann-Whitney U test, the differences for the categorical variables were analyzed by the Chi-Square test and the association between the continuous variables was analyzed by the Spearman Correlation test. The tests were two-tailed with a confidence level of 5%. RESULTS: Overall, the frequency of an overactive bladder was present in 117 (70.5%) of the participants. The body mass index (BMI) of the group with overactive bladder symptoms was significantly higher than the BMI of those without these symptoms (p=0.001). A higher prevalence of mild, moderate and severe anxiety was observed among older women with overactive bladder symptoms. In addition, the overactive bladder symptoms group presented a positive low correlation with anxiety symptoms (r=0.345) and with BMI (r=0.281). There was a small correlation between BMI and anxiety symptoms (r=0.164). CONCLUSIONS: Overactive bladder syndrome was prevalent among older women and the existence of these symptoms was linked to the presence of mild, moderate and/or severe anxiety symptoms. PMID- 25140571 TI - [Cross-cultural adaptation of the Pregnancy and Weight Gain Attitude Scale]. AB - PURPOSE: To present the cross-cultural adaptation to Brazilian Portuguese language of the Pregnancy and Weight Gain Attitude Scale. METHODS: This scale was developed in order to verify whether attitude toward thinness affects weight gain during pregnancy and contains statements that express different attitudes of pregnant women regarding their own weight gain. The procedures were: translation, back translation, comprehension evaluation, preparation of a final version, application of the scale to 180 pregnant women (mean age=29.6, gestational age=25.7 weeks) and psychometric analysis. RESULTS: Satisfactory equivalence between the versions and satisfactory internal consistency (Cronbach's alpha 0.7) were detected. The exploratory factor analysis suggested four subscales with 51.4% total variance explained. CONCLUSION: The scale proved to be valid and can be used in studies with pregnant women in Brazil to assess attitudes toward weight gain and to detect and prevent dysfunctional behaviors during pregnancy. PMID- 25140572 TI - [Changes in the extracellular matrix due to diabetes and their impact on urinary continence]. AB - The prevalence of urinary incontinence in diabetic pregnant women is significantly high two years after cesarean section. Incontinence can be the most common consequence of hyperglycemia compared to other complications. Thus, identifying the risk factors for the development of urinary incontinence in diabetes is the major aim in the prevention of this very common condition. Recent surveys have shown that not only muscle but also the urethral extracellular matrix play an important role in the mechanism of urinary continence. Translational work on rats by our research group showed that diabetes during pregnancy damages the extracellular matrix and urethral striated muscle, a fact that may explain the high prevalence of urinary incontinence and pelvic floor dysfunction in women with gestational diabetes mellitus. Diabetes affects the expression, organization and change in extracellular matrix components in different organs, and tissue remodeling and fibrosis appear to be a direct consequence of it. Therefore, understanding the impact of modifiable risk factors, such as diabetes, which involves using preventive strategies, can reduce the rates of urinary incontinence and the health care costs, and improve the quality of life of women, especially during pregnancy and postpartum. PMID- 25140573 TI - Allelic variants at codon 146 in the PRNP gene show significant differences in the risk for natural scrapie in Cypriot goats. AB - Previous studies have shown the association between the polymorphisms serine (S) or aspartic acid (D) at codon 146 of the PRNP gene and resistance to scrapie. All goats aged >12 months (a total of 1075 animals) from four herds with the highest prevalence of scrapie in the country were culled and tested, of which 234 (21.7%) were positive by either the rapid test or immunohistochemistry (IHC) for any of the tissues tested. The odds of scrapie infection occurring in NN146 goats was 101 [95% credible interval (CrI) 19-2938] times higher than for non-NN146 or unknown genotypes. IHC applied to lymphoreticular tissue produced the highest sensitivity (94%, 95% CrI 90-97). The presence of putatively resistant non-NN146 alleles in the Cypriot goat population, severely affected by scrapie, provides a potential tool to reduce/eradicate scrapie provided that coordinated nationwide breeding programmes are implemented and maintained over time. PMID- 25140576 TI - Influence of interfacial rheology on drainage from curved surfaces. AB - Thin lubrication flows accompanying drainage from curved surfaces surround us (e.g., the drainage of the tear film on our eyes). These draining aqueous layers are normally covered with surface-active molecules that render the free surface viscoelastic. The non-Newtonian character of these surfaces fundamentally alters the dynamics of drainage. We show that increased film stability during drainage can occur as a consequence of enhanced surface rheology. Increasing the surfactant layer viscosity decreases the rate of drainage; however, this retarding influence is most pronounced when the insoluble surfactant layer has significant elasticity. We also present a simple theoretical model that offers qualitative support to our experimental findings. PMID- 25140577 TI - Clinical significance of 2 h plasma concentrations of first-line anti tuberculosis drugs: a prospective observational study. AB - OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients with tuberculosis in Denmark and to determine the relationship between the concentrations and the clinical outcome. METHODS: After 6-207 days of treatment (median 34 days) 2 h blood samples were collected from 32 patients with active tuberculosis and from three patients receiving prophylactic treatment. Plasma concentrations were determined using LC-MS/MS. Normal ranges were obtained from the literature. Clinical charts were reviewed for baseline characteristics and clinical status at 2, 4 and 6 months after the initiation of treatment. At a 1 year follow-up, therapy failure was defined as death or a relapse of tuberculosis. RESULTS: Plasma concentrations below the normal ranges were frequently observed: isoniazid in 71%, rifampicin in 58%, ethambutol in 46%, pyrazinamide in 10% and both isoniazid and rifampicin in 45% of the patients. The plasma concentrations of isoniazid correlated inversely with the C-reactive protein level at the time of sampling (P = 0.001). During 1 year of follow-up, therapy failure occurred in five patients. Therapy failure occurred more frequently when the concentrations of isoniazid and rifampicin were both below the normal ranges (P = 0.013) and even more frequently when they were below the median 2 h drug concentrations obtained in the study (P = 0.005). CONCLUSIONS: At 2 h, plasma concentrations of isoniazid and rifampicin below the normal ranges were frequently observed. The inverse correlation between the plasma concentrations of isoniazid and C-reactive protein indicate a suboptimal treatment effect at standard dosing regimens. Dichotomization based on median 2 h drug concentrations was more predictive of outcome than dichotomization based on normal ranges. PMID- 25140578 TI - Molecular surveillance and prevalence of carbapenem-resistant Enterobacteriaceae in Northern Taiwan. PMID- 25140579 TI - Molecular basis of non-mutational derepression of ramA in Klebsiella pneumoniae. AB - OBJECTIVES: The ram locus, consisting of the romA-ramA genes, is repressed by the tetracycline-type regulator RamR, where regulation is abolished due to loss-of function mutations within the protein or ligand interactions. The aim of this study was to determine whether the phenothiazines (chlorpromazine and thioridazine) directly interact with RamR to derepress ramA expression. METHODS: Quantitative real-time PCR analyses were performed to determine expression levels of the romA-ramA genes after exposure to the phenothiazines. Electrophoretic mobility shift assays (EMSAs) and in vitro transcription experiments were performed to show direct binding to and repression by RamR. Direct binding of the RamR protein to the phenothiazines was measured by fluorescence spectroscopy experiments and molecular docking models were generated using the RamR crystal structure. RESULTS: Exposure to either chlorpromazine or thioridazine resulted in the up-regulation of the romA-ramA genes. EMSAs and in vitro transcription experiments demonstrated that both agents reduce/abolish binding and enhance transcription of the target PI promoter upstream of the ramR-romA genes in Klebsiella pneumoniae compared with RamR alone. Fluorescence spectroscopy measurements demonstrated that RamR directly binds both chlorpromazine and thioridazine with micromolar affinity. Molecular docking analyses using the RamR crystal structure demonstrated that the phenothiazines interact with RamR protein through contacts described for other ligands, in addition to forming unique strong polar interactions at positions D152 and K63. CONCLUSIONS: These data demonstrate that phenothiazines can modulate loci linked to the microbe-drug response where RamR is an intracellular target for the phenothiazines, thus resulting in a transient non-mutational derepression of ramA concentrations. PMID- 25140580 TI - Premenstrual syndrome in Turkish medical students and their quality of life. AB - This study aimed to analyse the frequency and symptoms of premenstrual syndrome (PMS) and its effect on quality of life in medical students. Sociodemographic data, a symptom calendar for the following consecutive two menstrual periods and SF-36 quality of life questionnaire were collected. A total of 228 students joined the survey. The average age of the students was 20.77 +/- 1.90. The frequency of PMS was 91.8%. The most frequent symptoms were abdominal bloating (89.5%), irritability (88.3%) and breast tenderness (82.6%). Quality of life scores ranged from 17.00 to 97.00 and were lowest in the severe PMS group. Alcohol consumption, stress events and fat rich diets increased the severity of PMS. Family history significantly affected the severity of PMS and quality of life scores. Premenstrual syndrome was found to be a frequent entity among medical students and seemed to affect quality of life in a moderate way. PMID- 25140581 TI - The interprofessional clinical experience: interprofessional education in the nursing home. AB - The interprofessional clinical experience (ICE) was designed to introduce trainees to the roles of different healthcare professionals, provide an opportunity to participate in an interprofessional team, and familiarize trainees with caring for older adults in the nursing home setting. Healthcare trainees from seven professions (dentistry, medicine, nursing, nutrition, occupational therapy, optometry and social work) participated in ICE. This program consisted of individual patient interviews followed by a team meeting to develop a comprehensive care plan. To evaluate the impact of ICE on attitudinal change, the UCLA Geriatric Attitudes Scale and a post-experience assessment were used. The post-experience assessment evaluated the trainees' perception of potential team members' roles and attitudes about interprofessional team care of the older adult. Attitudes toward interprofessional teamwork and the older adult were generally positive. ICE is a novel program that allows trainees across healthcare professions to experience interprofessional teamwork in the nursing home setting. PMID- 25140583 TI - Herpes Simplex Keratitis in Rheumatoid Arthritis Patients. AB - PURPOSE: To describe a series of 5 patients with herpes simplex virus keratitis (HSK) and rheumatoid arthritis (RA) under immunosuppressive treatment. METHODS: Retrospective study. Detailed data were obtained regarding symptoms and signs at the initial evaluation, treatment, microbiological diagnostic tests, evolution, and outcomes. RESULTS: Five patients with HSK and RA were identified. Bilateral involvement occurred in 2 patients (40%). Epithelial keratitis was diagnosed in 5 eyes. Three eyes showed severe melting with eye perforation. Gram-positive bacterial co-infections were common in the group with stromal keratitis. We did not find differences in the evolution of the disease based on anti-rheumatoid treatment. CONCLUSIONS: The characteristics of HSK in patients with RA differed from HSK in immunocompetent patients. The stromal keratitis cases were very aggressive and difficult to manage, with perforation and gram-positive bacterial co-infection as frequently associated conditions. Prophylactic therapy at standard doses was unsuccessful to avoid recurrences. PMID- 25140582 TI - Reemergence of hedgehog mediates epithelial-mesenchymal crosstalk in pulmonary fibrosis. AB - Hedgehog signaling plays important roles in cell development and differentiation. In this study, the ability of Sonic Hedgehog (SHH) to induce myofibroblast differentiation was analyzed in isolated human lung fibroblasts, and its in vivo significance was evaluated in rodent bleomycin-induced pulmonary fibrosis. The results showed that SHH could induce myofibroblast differentiation in human lung fibroblasts in a Smo- and Gli1-dependent manner. Gel shift analysis, chromatin immunoprecipitation assay, and site-directed mutagenesis revealed that a Gli1 binding consensus in the alpha-SMA gene promoter was important for mediating SHH induced myofibroblast differentiation. Analysis of Hedgehog reemergence in vivo revealed that of all three Hedgehog isoforms, only SHH was significantly induced in bleomycin-injured lung along with Gli1. The induction of SHH was only noted in epithelial cells, and its expression was undetectable in lung fibroblasts or macrophages. transforming growth factor (TGF)-beta induced SHH significantly in cultured alveolar epithelial cells, whereas SHH induced TGF-beta in lung fibroblasts. Pulmonary fibrosis and alpha-smooth muscle actin (alpha-SMA) expression were significantly reduced in mice that were Smo deficient only in type I collagen-expressing cells. Thus, the reemergence of SHH in epithelial cells could result in induction of myofibroblast differentiation in a Smo dependent manner and subsequent Gli1 activation of the alpha-SMA promoter. PMID- 25140584 TI - The effect of prasugrel on ADP-stimulated markers of platelet activation in patients with sickle cell disease. AB - Platelets of patients with sickle cell disease (SCD) show evidence of mild activation in the non-crisis steady state and greater activation during vaso occlusive crises (VOC). Prasugrel, a potent inhibitor of ADP-mediated platelet activation and aggregation, may be useful in attenuating VOC. We compared platelet responses to ADP stimulation in patients with SCD and healthy subjects before and after treatment with prasugrel. In a phase 1 study, platelet biomarker levels were assessed in 12 adult patients with SCD and 13 healthy subjects before and after 12 +/- 2 days of 5.0 or 7.5 mg/day prasugrel. The following were determined in whole blood samples stimulated with 20 uM ADP: (i) percentages of monocytes and neutrophils with adherent platelets (cell-platelet aggregates); (ii) the relative number (mass) of platelets associated with each monocyte and neutrophil as reported by CD61 mean fluorescence intensity (MFI) of the monocyte platelet and neutrophil-platelet aggregates; (iii) the percentages of platelets positive for surface expression of CD40 ligand (CD40L), P-selectin (CD62p) and activated glycoprotein IIb-IIIa (GPIIb-IIIa); and (iv) the percentages of platelets and monocyte-platelet aggregates positive for surface tissue factor (TF) expression. At baseline, there were no significant differences between cohorts in the percentages of platelets expressing activation biomarkers. Following 12 days of prasugrel administration, the percentages of platelets expressing activation biomarkers following ADP stimulation were reduced in both cohorts, and there were no significant differences between groups. Both patients with SCD and healthy subjects had significant reductions in the monocyte-platelet and neutrophil-platelet aggregate MFI and the percentage of platelets expressing P-selectin and activated GPIIb-IIIa (all p < 0.05). Healthy subjects also had significant reductions in monocyte-platelet aggregate percentages (p = 0.004), neutrophil-platelet aggregate percentages (p = 0.011) and the percentage of CD40L positive platelets (p = 0.044) that were not observed in patients with SCD. Prasugrel administration to SCD patients attenuates ex vivo ADP-stimulated platelet activation as measured by the percentage of platelets positive for P selectin and GPIIb-IIIa, thus reducing the proportion of platelets that may participate in aggregates. Furthermore, prasugrel decreases ex vivo ADP stimulated platelet aggregation with monocytes and neutrophils as measured by the monocyte-platelet and neutrophil-platelet aggregate MFI. This implies that in the presence of prasugrel, fewer platelets adhere to monocytes and neutrophils, which may result in reducing cell-platelet aggregate size. Therefore, reduced platelet reactivity and decreased size of leukocyte-platelet aggregates suggest additional mechanisms by which prasugrel may provide benefit to patients with SCD and support further investigation of possible therapeutic benefits of prasugrel in this population. PMID- 25140585 TI - Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic disorder comorbid with alcohol use disorder: a comparison with standard treatment. AB - OBJECTIVES: Dorsolateral prefrontal cortex (DLPFC) is dysfunctional in mood and substance use disorders. We predicted higher efficacy for add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS), compared with standard drug treatment (SDT) in patients with dysthymic disorder (DD)/alcohol use disorder (AUD) comorbidity. METHODS: We carried-out a 6-month open-label study involving 20 abstinent patients with DSM-IV-TR AUD comorbid with previously developed DD. Ten patients received SDT for AUD with add-on bilateral dTMS (dTMS-AO) over the DLPFC, while another 10 received SDT alone. We rated alcohol craving with the Obsessive Compulsive Drinking Scale (OCDS), depression with the Hamilton Depression Rating Scale (HDRS), clinical status with the Clinical Global Impressions scale (CGI), and global functioning with the Global Assessment of Functioning (GAF). RESULTS: At the end of the 20-session dTMS period (or an equivalent period in the SDT group), craving scores and depressive symptoms in the dTMS-AO group dropped significantly more than in the SDT group (P < 0.001 and P < 0.02, respectively). CONCLUSIONS: High frequency bilateral DLPFC dTMS with left preference was well tolerated and found to be effective as add-on in AUD. The potential of dTMS for reducing craving in substance use disorder patients deserves to be further investigated. PMID- 25140586 TI - Impact of lifetime psychiatric diagnosis on long-term retention and survival of former opiate addicts in methadone maintenance treatment. AB - OBJECTIVES: To characterize lifetime psychiatric diagnosis groups among methadone maintenance treatment (MMT) patients and associations of diagnosis to long-term (up to 20 years) retention and survival either during treatment or post discontinuation. METHODS: A total of 758 patients with available psychiatric diagnosis (98% of those ever admitted between June 1993 and June 2012) were followed-up until June 2013. Lifetime psychiatric diagnosis was assessed according to DSM-IV-TR (Axis I, II, I & II, or none). Observed urine samples at 1 and 13 months were positive for drugs if at least one was positive. Survival data were based on the Israel National Population Registry. Survival and retention in MMT were compared (Kaplan Meier) between groups. RESULTS: The Axis II (personality disorders) group had the worst mean long-term retention (5.8 years, 95% Confidence Interval (CI) 5.0-6.5) compared with the Axis I, Axis I & II or no psychiatric diagnosis groups (9.6 years, 95% CI 8.8-10.4) (P < 0.0005). Mean survival since admission (16.4 years, 95% CI 15.9-16.9) was similar for all groups. Axis II patients included more males, more drug injectors, were younger at initial opiate use and more likely left treatment before 1 year. CONCLUSIONS: Personality and coping mechanisms (Axis II) could be significant obstacles to the success of MMT, warranting special interventions to overcome them. PMID- 25140588 TI - Isolation and characterization of mesenchymal progenitors derived from the bone marrow of goats native from northeastern Brazil. AB - PURPOSE: To characterize bone marrow progenitors cells grown in vitro, using native goats from northeastern Brazil as animal model. METHODS: Ten northeastern Brazil native goats of both genders were used from the Piaui Federal University Agricultural Science Center's (UFPI) - Goat Farming Sector. Bone marrow aspirates where taken from the tibial ridge and seeded on culture plates for isolation, expansion and Flow Cytometry (expression markers - Oct-3/4, PCNA, Ck-Pan, Vimentina, Nanog). RESULTS: Progenitor cells showed colonies characterized by the presence of cell pellets with fibroblastoid morphology. Cell confluence was taken after 14 days culture and the non-adherent mononuclear cell progressive reduction. After the first passage, 94.36% cell viability was observed, starting from 4.6 x 106 cell/mL initially seeded. Cells that went through flow cytometry showed positive expression for Oct-3/4, PCNA, Ck-Pan, Vimentina, and Nanog. CONCLUSIONS: Bone marrow progenitor isolated of native goats from northeastern Brazil showed expression markers also seen in embryonic stem cells (Oct-3/4, Nanog), markers of cell proliferation (PCNA) and markers for mesenchymal cells (Vimentina and Ck-pan), which associated to morphological and culture growth features, suggest the existence of a mesenchymal stem cell (MSC) population in the goat bone marrow stromal cells studied. PMID- 25140587 TI - Effect of a brief seated massage on nursing student attitudes toward touch for comfort care. AB - BACKGROUND: While massage has been removed from nursing curricula, studies have reported massage as safe and effective for stress reduction, relaxation, pain relief, fatigue, and quality of life. OBJECTIVE: To compare the efficacy of two intensities of touch administered during two seated massages on the attitudes of nursing students toward touch for their self-care and patient care. PARTICIPANTS: Nursing students who volunteered gave institutional review board-approved written informed consent to undergo massage by a licensed massage therapist. SETTINGS/LOCATION: A private room adjacent to the nursing lab in a school of nursing. INTERVENTION: Brief seated massages of differing intensities. Each participant received low-intensity and high-intensity touch in a two-block, randomized order, within-subjects design. Linear mixed models nested within subject and random intercept analyses were used to test hypotheses in this two treatment, two-sequence, two-period crossover design. OUTCOME MEASURES: Health questionnaires/visual analogue scales pertaining to physical/affective/and attitudinal status were completed before and after each massage. RESULTS: Twenty nine participants (93% female, 83% single) completed the study. Before massage, the optimal intensity of touch anticipated for self-comfort was 6.6 (0=no pressure;10=most intense pressure imaginable). The mean touch intensities were 6.7 for high-intensity massage and 0.5 for low-intensity (p<0.001). The overall percentage differences (feeling better or worse) following massage were as follows: low intensity, 37.5% better; high intensity, 62.7% better (p<0.001). Significantly more improvement was reported for energy, pain, stress, and feeling physically uptight after high-intensity compared with low-intensity (p<0.03). Participants were more likely to both receive touch for self-care and provide touch for patient care after experiencing high- versus low-intensity massage (p<0.01). CONCLUSIONS: High-intensity seated massage was more efficacious than low-intensity massage and positively influenced nursing student attitudes toward the inclusion of massage in self-care/patient care. The role of touch for self care/patient care in the nursing curricula merits reconsideration. PMID- 25140589 TI - Light-emitting diode effects on combined decellularization of tracheae. A novel approach to obtain biological scaffolds. AB - PURPOSE: To obtain a decellularized tracheal scaffold associating traditional approaches with the novel light-emitting diode (LED) proposal. METHODS: This study was performed with New Zealand adult rabbits weighing 3.0 - 4.0 kg. Different protocols (22) were used combining physical (agitation and LED irradiation), chemical (SDS and Triton X-100 detergents), and enzymatic methods (DNase and RNase). RESULTS: Generally, the cells surrounding soft tissues were successfully removed, but none protocol removed cells from the tracheal cartilage. However, longer protocols were more effective. The cost-benefits relation of the enzymatic processes was not favorable. It was possible to find out that the cartilaginous tissue submitted to the irradiation with LED 630nm and 475 nm showed an increased number of gaps without cells, but several cells were observed to be still present. CONCLUSION: The light-emitting diode is a promising tool for decellularization of soft tissues. PMID- 25140590 TI - The establishment and evaluation of rabbit model for peripherally inserted central catheter. AB - PURPOSE: To establish a model to simulate the clinical specific process of peripherally inserted central catheter (PICC) on rabbits, and detect how long the catheter can be indwelled. METHODS: Seventeen healthy New Zealand white rabbits were inserted the PICC according to the clinical specific procedure. With the principle of random, the rabbits were divided into four groups (14d, 21d, 28d, 35d). Each group contains four rabbits, and Group 1 was served as blank control group. When finishing the experiment, we took the blood vessels which was inserted the catheter and observed the changes of vascular endothelium using the Hematoxylin-Eosin (HE) staining. RESULTS: 90% animals were succeeded in inserting PICC. Early signs of endovascular inflammation were predominantly neutrophils, then mainly monocytes, visible fibrous tissue hyperplasia of the vessel wall, vascular endothelial proliferation and granuloma formation. And after that the irreversible changes in the blood vessels could be observed, especially five weeks after catheterization. CONCLUSIONS: We have succeeded in establishing the rabbit model for peripherally inserted central catheter, and provided a new way for nursing teaching and training. Since the irreversible changes of the vascular endothelium, it is recommended that the time of indwelling is not more than five weeks on animal. PMID- 25140591 TI - Effects of traction on the spermatic cord of rats. AB - PURPOSE: To determine whether tension in the spermatic cord of rats causes lesions in the testis, epididymis or vas deferens. METHODS: Forty Wistar rats were randomly allocated into four groups. A traction force of 1.6 Newton (N) in group I and 1 N in group II was applied to the right spermatic cord. Group III was the sham, and group IV served as the control. RESULTS: Testicular lesions occurred on the right side in 66.7% of the rats and on the left side in 46.1% of the rats. The testes showed a decreased number of Sertoli cells, necrosis and a decreased number of germ cells in the seminiferous tubules. Anatomopathological changes in the vas deferens were not identified. There was no decrease in the thickness of the muscle wall of the vas deferens. In the right epididymis, 71.8% of the animals showed a reduction and 5% showed an absence of intraluminal sperm. In the left epididymis, 37.5% of the rats showed a reduction. The volume and the final testicular weight of the right side in group IV was different from those in the other groups. CONCLUSIONS: Anatomopathological lesions were found in the testis and epididymis. PMID- 25140592 TI - Analysis of the histology of the scar bladder and biochemical parameters of rats with a solitary kidney undergoing immunosuppression with tacrolimus. AB - PURPOSE: To evaluate bladder histology in healing and biochemical analysis of rats with single kidney in ischemia/reperfusion, treated with tacrolimus. METHODS: Fifty rats randomized into five groups. Three rats died in surgery, 47 rats divided in groups: Control (non-operated, n=10), Sham (operated without drugs, n=8), T1 (operated + tacrolimus 1mg/kg, n=10), T2 (operated + tacrolimus 0.1 mg/kg, n=10), T3 (operated + tacrolimus 10mg/kg, n=9). The surgery was: laparotomy, right nephrectomy, left kidney ischemia/reperfusion, cystotomy followed by bladder suture. After that, rats were submited to gavage daily (Control and Sham with saline solution. T1, T2, T3 with tacrolimus in doses already mentioned). On the 14th day, after death induction, cystectomy was performed and bladder was histologicaly analysed. The serum urea, creatinine and tacrolimus were analysed too. RESULTS: There was difference in serum tacrolimus in T3 compared to the other groups (p<0.05). There was higher doses of creatinine in T3 group and higher urea in groups with tacrolimus. There were significant differences among all histologic variables comparing groups with and without tacrolimus (p<0.05). CONCLUSION: Tacrolimus associated with ischemia/reperfusion is nephrotoxic, suppresses inflammation and seems to delay the healing bladder. PMID- 25140593 TI - Effect of allopurinol on the kidney function, histology and injury biomarker (NGAL, IL 18) levels in uninephrectomised rats subjected to ischaemia-reperfusion injury. AB - PURPOSE: To investigate whether allopurinol exerts a protective effect on kidneys by measuring new kidney injury biomarkers (NGALp, NGALu, KIM 1 and IL 18) and analysing the renal function and histology in uninephrectomised rats subjected to ischaemia-reperfusion injury. METHODS: Thirty two Wistar rats were randomly allocated to four groups: Sham (S): laparotomy; Control (C): laparotomy and ischaemia-reperfusion in the left kidney; Control Allopurinol (CA): laparotomy and allopurinol at a dose of 100mg.kg 1.d 1; and Allopurinol (A): laparotomy ischaemia-reperfusion in the left kidney and allopurinol at a dose of 100mg.kg 1.d 1. The NGALp, NGALu, KIM 1, IL 18 and creatinine levels and the kidney histology were analysed. The significance level was established as p<0.05. RESULTS: Creatinine level increased in all the groups, with A ~ C > S ~ CA. The NGALp, NGALu and IL 18 levels exhibited similar behaviour in all the groups. KIM 1 was higher in group A than C and showed intermediate values in groups S and CA. Severity of injury in the left kidney was greater in groups C and A compared to S and CA. CONCLUSION: Allopurinol did not exert protective or damaging effects on the kidneys of rats subjected to ischaemia-reperfusion injury. PMID- 25140594 TI - Effect of vitamin K1 supplementation on left colon healing in rats with extrahepatic biliary obstruction. AB - PURPOSE: To evaluate the effects of vitamin K1 on wound healing in the left colon of rats with experimental biliary obstruction. METHODS: Sixteen male rats, divided into four groups of four animals each (L, M, LK, and MK), underwent colostomy followed by bowel suture in the left colon. Seven days before, animals in the L and LK groups had undergone common bile duct ligation. The animals in groups MK and LK received vitamin K1 supplementation. On day 7 after bowel suture, repeat laparotomy was performed for evaluation of colonic healing by burst pressure measurement and collection of samples for histopathological analysis. Changes in body weight were evaluated in the four groups. RESULTS: Weight loss was lower in animals supplemented with vitamin K. No significant differences were observed in burst pressure among the four groups (p>0.05). Histological analysis showed more hemorrhage and congestion in the biliary obstruction groups. Supplemented animals exhibited increased collagen formation and less edema and abscess formation. CONCLUSION: Vitamin K supplementation attenuated weight loss and improved colonic wound healing in rats. PMID- 25140595 TI - Copaiba oil effect under different pathways in mice subjected to sepsis. AB - PURPOSE: To evaluate the effects of copaiba oil administered by different routes on survival of mices subjected to cecal ligation and puncture. METHODS: Thirty two mice were distributed into four study groups (N=8): Sham group: normal standard animals; CONTROL GROUP: submitted a cecal ligation and puncture (CLP); Gavage group: submitted a CLP, and treat with copaiba oil by gavage; and Subcutaneous group: submitted a CLP, and treat with copaiba oil by subcutaneous injection. After the death of the histological analysis were performed. The Kaplan-Meier curves of surviving time were realized. RESULTS: All animals that received copaiba, regardless of the route used, survived longer when compared to the control group (p<0.0001), whereas the survival time ranged from 20 hours for the control group up to 32 hours for the animals of gavage group and 52 for subcutaneous group. The animals that received gavage copaiba lived about and about 20 hours unless the subcutaneous group (p=0.0042). There was no statistical difference when compared the intensity of inflammatory response (p>0.05) CONCLUSION: Prophylactic subcutaneous administration of copaiba in mice subjected to severe sepsis by cecal ligation and puncture, resulted in a survival time higher than non-use or use of this oil by gavage. PMID- 25140596 TI - Face transplantation in rats. Reproducibility of the experimental model in Brazil. AB - PURPOSE: To investigate the reproducibility of the experimental model of face allotransplantation in rats in Brazil. METHODS: Eighteen rats were operated, nine nine donors recipients. Animals underwent transplantation of the left hemiface, with periorbital and scalp. Transplants were made from donor Wistar rats to recipients Lewis rats. Flaps were based on the common carotid artery and the external jugular vein of the donor animal and the anastomosis in the recipient area was performed in common carotid artery (end-to-side) and in external jugular vein (end-to-end). RESULTS: Of the nine recipient animals operated, six survived and three progressed to death in the first days after surgery (survival rate = 67%). The mean time of the procedure was 252 minutes and the mean time of flap ischemia was 95 minutes. The five surviving animals were sacrificed at 14 days, in good general condition and without signs of tissue rejection. CONCLUSIONS: The experimental model of face allotransplantation in rats is reproducible in our midst. Duration of surgery, time of flap ischemia, animal survival rate and complications observed were similar to those described in the literature. PMID- 25140597 TI - Nutraceutical preconditioning with arginine and oil mixes. Effects on inflammatory mediators, oxidative stress and lipid profile in patients undergoing radical prostatectomy. AB - PURPOSE: To investigate whether there is any effect resulting from preconditioning with nutraceutical supplementation containing arginine and oil mixes with high omega9:omega6 ratio and low omega6:omega3 ratio containing EPA and DHA, ALA fatty acids on inflammatory mediators, antioxidant and lipid profile modulation in surgical trauma. METHODS: Twenty-six men scheduled for radical prostatectomy were randomized into three groups and treated as follows: Group 1 (skim milk, 0% fat), Group 2 (supplement with omega6:omega3 ratio of 8:1 and arginine) and Group 3 (supplement with high omega9:omega6 ratio of 3.2:1 and low omega6:omega3 ratio of 1.4:1 and arginine). Patients received skin milk or supplements twice a day (200 ml) during five days prior to surgery. Peripheral venous blood samples were collected at three different timepoints: five days before surgery (PRE), before anesthesia induction (IND) and on the 2nd postoperative day (POS). Parameters analyzed included inflammatory cytokines (IL 1beta, IL-6, IL-8 and TNF-alpha), antioxidants (catalase), lipid profile and heat shock protein (HSP-27). RESULTS: There were no significant differences between groups on inflammatory mediators and antioxidant parameters. However, lipid profile values (Cholesterol, LDL, Triglycerides, VLDL), were significantly different. CONCLUSION: Preconditioning with arginine and oil mixes containing high omega9:omega6 ratio and low omega6:omega3 ratio, has no effects on inflammatory mediators and oxidative stress in patients undergoing radical prostatectomy. Reduction of cholesterol, triglycerides, LDL and VLDL profiles may be related to the trauma effect. PMID- 25140598 TI - Zero prevalence of vancomycin-resistant enterococci among Swedish preschool children. AB - OBJECTIVES: Enterococci are a natural part of the bacterial flora of humans, animals, and insects and are frequently found in the community. Vancomycin resistant enterococci (VRE) have emerged as a growing problem, associated with high morbidity and mortality. The aim of this study was to investigate the prevalence of VRE among healthy Swedish preschool children and ascertain whether they constitute a reservoir for the bacteria. METHODS: In total, 313 individual diapers were collected from preschools in Uppsala, Sweden. Fecal samples were screened by analyzing the color change in a broth followed by polymerase chain reaction for vanA and vanB genes, which are associated with vancomycin resistance. RESULTS: Neither vanA nor vanB genes could be detected from the samples. CONCLUSIONS: Preschool children in Uppsala do not constitute a reservoir for VRE. The zero prevalence is consistent with the overall decline in VRE prevalence in Sweden during the last years. PMID- 25140600 TI - Modelling and control of cholera on networks with a common water source. AB - A mathematical model is formulated for the transmission and spread of cholera in a heterogeneous host population that consists of several patches of homogeneous host populations sharing a common water source. The basic reproduction number R0 is derived and shown to determine whether or not cholera dies out. Explicit formulas are derived for target/type reproduction numbers that measure the control strategies required to eradicate cholera from all patches. PMID- 25140599 TI - Deferoxamine but not dexrazoxane alleviates liver injury induced by endotoxemia in rats. AB - The purpose of the present study was to compare the activity of two different clinically available iron chelators on the development of acute liver injury after administration of the bacterial endotoxin (lipopolysaccharide [LPS]) in rats. Lipopolysaccharide was administered either alone or after pretreatment with dexrazoxane (DEX) or deferoxamine (DFO). Control groups received only saline or its combination with either chelator. After 8 h, untreated LPS rats developed liver injury, with signs of inflammation and oxidative stress. Lipopolysaccharide reduced plasma iron concentrations in association with increased production of hepcidin and the reduced liver expression of ferroportin. Administration of chelating agents to LPS animals showed distinct effects. Although both drugs were able to reduce liver iron content, together with corresponding changes in hepcidin and ferroportin expressions, only DFO showed a protective effect against liver injury despite relatively small liver concentrations. In sharp contrast, DEX failed to improve any hallmark of liver injury and even worsened the GSH/GSSG ratio, the indicator of oxidative stress in the tissue. High-performance liquid chromatography-mass spectrometry analysis showed marked liver accumulation of iron-chelating metabolite of DEX (ADR-925), whereas the parent compound was undetectable. Further downregulation of transporters involved in bile formation was observed after DFO in the LPS group as well as in healthy animals. Neither chelator imposed significant liver injury in healthy animals. In conclusion, we demonstrated marked differences in the modulation of endotoxemic liver impairment between two iron chelators, implicating that particular qualities of chelating agents may be of crucial importance. PMID- 25140601 TI - Validation of a French (Quebec) version of the Tinnitus Handicap Inventory. AB - OBJECTIVE: To assess the psychometric properties of the Quebec French translation of the Tinnitus Handicap Inventory (THI-FQ). DESIGN: The original version of the THI was translated into French by two different people, and then revised before being administered to 221 study participants. A subgroup of 75 participants also completed the French versions of the Beck Depression Inventory II (BDI-II) and the Tinnitus Reaction Questionnaire (TRQ). STUDY SAMPLE: The study participants used French as their home language, had completed an otolaryngology (ENT) assessment, and had sought help with disabling tinnitus. RESULTS: No differences were found according to gender, age, or degree of hearing loss. The THI-FQ was very stable over a period of approximately 32 days. Internal consistency was 0.93 for the total score. Convergent validity with the TRQ was 0.81 (p < 0.001) while construct validity, as obtained with the BDI-II, was 0.74 (p < 0.001). As in other studies, the factor analysis did not confirm the structure proposed by Newman et al in the original study (1996). CONCLUSIONS: The THI-FQ presents very good reliability and validity, comparable to translations in other languages and the original version. PMID- 25140602 TI - Investigation of a matrix sentence test in noise: reproducibility and discrimination function in cochlear implant patients. AB - OBJECTIVE: The aim of this study was to describe common properties (reproducibility, discrimination function, and its steepness) of matrix tests used for cochlear implant (CI) users and to obtain data for the German-language version matrix test, the Oldenburg sentence test (OLSA), presented in noise. DESIGN: The speech reception thresholds (SRT) in noise were measured by means of an adaptive test procedure, and by measurement at various signal-to-noise ratios to determine the course of the entire discrimination function per subject. STUDY SAMPLE: The measurements were performed on 38 CI users fitted with a Cochlear(TM) Freedom((r)) or a Cochlear(TM) Nucleus((r)) 5 CI system. RESULTS: The test-retest reproducibility showed a significant dependence on the SRT in noise. For the better performers, the test-retest difference was found to be smaller, while for the poorer performers the difference increased. For the better performers, the slope of the discrimination function at SRT (s50) was comparable to that for individuals with normal hearing, while for the poorer performers the s50 tended to be significantly reduced. CONCLUSIONS: As the CI users differed significantly in their SRT and their s50, a unified discrimination function for CI users must not be used. Further tailoring of the procedure may be required, especially for poorer CI performers. PMID- 25140603 TI - Reply from Theelen-van den Hoek, et al. PMID- 25140604 TI - Effectiveness of questionnaires for screening hearing of school-age children: a comprehensive literature review. AB - OBJECTIVE: The purpose of this study was to review the literature on the effectiveness of parent or teacher-completed questionnaires as a tool to screen school-aged children for permanent hearing loss. DESIGN: A rapid evidence assessment was completed to provide a summary of information published between 1980 and 2013 in English or Spanish. To identify relevant publications, a database search was conducted using nine databases. STUDY SAMPLE: Seven studies were identified for inclusion in the review. RESULTS: Authors of three of the studies recommended use of the questionnaire as a method for screening hearing in school-aged children, and authors of four of the studies did not recommend use of the questionnaire. However, only one of the seven studies provided good evidence that questionnaires are an effective way of identifying hearing loss among children. CONCLUSIONS: There is insufficient evidence that parent or teacher completed questionnaire screening can be reliably used to identify children in need of further hearing assessment. It is clear that more research is needed before concluding that questionnaires are an effective and low-cost tool for use to screen children for permanent hearing loss. PMID- 25140605 TI - Rationally designed, nontoxic, nonamyloidogenic analogues of human islet amyloid polypeptide with improved solubility. AB - Human islet amyloid polypeptide (hIAPP or amylin) is a polypeptide hormone produced in the pancreatic beta-cells that plays a role in glycemic control. hIAPP is deficient in type 1 and type 2 diabetes and is a promising adjunct to insulin therapy. However, hIAPP rapidly forms amyloid, and its strong tendency to aggregate limits its usefulness. The process of hIAPP amyloid formation is toxic to cultured beta-cells and islets, and islet amyloid formation in vivo has been linked to beta-cell death and islet graft failure. An analogue of hIAPP with a weakened tendency to aggregate, denoted pramlintide (PM), has been approved for clinical applications, but suffers from poor solubility, particularly at physiological pH, and its unfavorable solubility profile prevents coformulation with insulin. We describe a strategy for rationally designing analogues of hIAPP with improved properties; key proline mutations are combined with substitutions that increase the net charge of the molecule. An H18R/G24P/I26P triple mutant and an H18R/A25P/S28P/S29P quadruple mutant are significantly more soluble at neutral pH than hIAPP or PM. They are nonamyloidogenic and are not toxic to rat INS beta cells. The approach is not limited to these examples; additional analogues can be designed using this strategy. To illustrate this point, we show that an S20R/G24P/I26P triple mutant and an H18R/I26P double mutant are nonamyloidogenic and significantly more soluble than human IAPP or PM. These analogues and second generation derivatives are potential candidates for the coformulation of IAPP with insulin and other polypeptides. PMID- 25140606 TI - Total syntheses of multicaulins via oxidative photocyclization of stilbenes. AB - The Wittig reaction of 3-isopropyl-4-methoxybenzaldehyde and 2,3 dimethylbenzylphosphonium bromide afforded the corresponding stilbene mixture 16. Oxidative photocyclization of stilbene 16 with iodine facilitated the first total synthesis of 7-isopropyl-6-methoxy-1,2-dimethylphenanthrene, multicaulin (1). The O-demethylation of 1 with BBr3 afforded the 7-isopropyl-1,2-dimethylphenanthren-6 ol, O-demethylmulticaulin (2). PMID- 25140609 TI - Quantum yields and reaction times of photochromic diarylethenes: nonadiabatic ab initio molecular dynamics for normal- and inverse-type. AB - Photochromism is a light-induced molecular process that is likely to find its way into future optoelectronic devices. In further optimization of photochromic materials, light-induced conversion efficiencies as well as reaction times can usually only be determined once a new molecule was synthesized. Here we use nonadiabatic ab initio molecular dynamics to study the electrocyclic reaction of diarylethenes, comparing normal- and inverse-type systems. Our study highlights that reaction quantum yields can be successfully predicted in accord with experimental findings. In particular, we find that inverse-type diarylethenes show a significantly higher reaction quantum yield and cycloreversion on times typically as short as 100 fs. PMID- 25140607 TI - Stochastic kinetics on networks: when slow is fast. AB - Most chemical and biological processes can be viewed as reaction networks in which different pathways often compete kinetically for transformation of substrates into products. An enzymatic process is an example of such phenomena when biological catalysts create new routes for chemical reactions to proceed. It is typically assumed that the general process of product formation is governed by the pathway with the fastest kinetics at all time scales. In contrast to the expectation, here we show theoretically that at time scales sufficiently short, reactions are predominantly determined by the shortest pathway (in the number of intermediate states), regardless of the average turnover time associated with each pathway. This universal phenomenon is demonstrated by an explicit calculation for a system with two competing reversible (or irreversible) pathways. The time scales that characterize this regime and its relevance for single-molecule experimental studies are also discussed. PMID- 25140610 TI - A Cu(II) complex of an imidazolium-based ionic liquid: synthesis, X-ray structure and application in the selective electrochemical sensing of guanine. AB - An imidazolium-based ionic liquid containing a carboxylic acid group was synthesized and complexed with Cu(II). The resulting complex R1 was fully characterized using various techniques, including IR spectroscopy and X-ray crystallography. Binding studies of the complex R1 were performed with anions and biomolecules using cyclic voltammetry, which showed no change in its voltammogram upon the addition of various anions and most biomolecules. However, a shift in the reduction peak from +0.20 to -0.15 was observed upon the addition of guanine. This selective determination of guanine by R1 was extended by using R1 as an electrochemical sensor for guanine in various voltammetric techniques, including cyclic voltammetry, LSV and DPV. The proposed sensor showed excellent reproducibility and high selectivity and sensitivity towards guanine, with a linear range of 0-20 MUM and a detection limit of 45 nM. PMID- 25140611 TI - Transparent metallic fractal electrodes for semiconductor devices. AB - Nanostructured metallic films have the potential to replace metal oxide films as transparent electrodes in optoelectronic devices. An ideal transparent electrode should possess a high, broadband, and polarization-independent transmittance. Conventional metallic gratings and grids with wavelength-scale periodicities, however, do not have all of these qualities. Furthermore, the transmission properties of a nanostructured electrode need to be assessed in the actual dielectric environment provided by a device, where a high-index semiconductor layer can reflect a substantial fraction of the incident light. Here we propose nanostructured aluminum electrodes with space-filling fractal geometries as alternatives to gratings and grids and experimentally demonstrate their superior optoelectronic performance through integration with Si photodetectors. As shown by polarization and spectrally resolved photocurrent measurements, devices with fractal electrodes exhibit both a broadband transmission and a flat polarization response that outperforms both square grids and linear gratings. Finally, we show the benefits of adding a thin silicon nitride film to the nanostructured electrodes to further reduce reflection. PMID- 25140613 TI - Molybdenum phosphide: a new highly efficient catalyst for the electrochemical hydrogen evolution reaction. AB - Molybdenum phosphide was adopted as a new electrocatalyst for the hydrogen evolution reaction for the first time, exhibiting an excellent electrocatalytic activity with a small Tafel slope of 60 mV dec(-1), which is amongst the most active, acid-stable, earth abundant HER electrocatalysts reported to date. PMID- 25140614 TI - Facile surface functionalization of hydrophobic magnetic nanoparticles. AB - Nonpolar phase synthesized hydrophobic nanocrystals show attractive properties and have demonstrated prominent potential in biomedical applications. However, the preparation of biocompatible nanocrystals is made difficult by the presence of hydrophobic surfactant stabilizer on their surfaces. To address this limitation, we have developed a facile, high efficiency, single-phase and low cost method to convert hydrophobic magnetic nanoparticles (MNPs) to an aqueous phase using tetrahydrofuran, NaOH and 3,4-dihydroxyhydrocinnamic acid without any complicated organic synthesis. The as-transferred hydrophilic MNPs are water soluble over a wide pH range (pH = 3-12), and the solubility is pH-controllable. Furthermore, the as-transferred MNPs with carboxylate can be readily adapted with further surface functionalization, varying from small molecule dyes to oligonucleotides and enzymes. Finally, the strategy developed here can easily be extended to other types of hydrophobic nanoparticles to facilitate biomedical applications of nanomaterials. PMID- 25140615 TI - High-resolution Fourier transform ion cyclotron resonance mass spectrometry with increased throughput for biomolecular analysis. AB - A multielectrode ion cyclotron resonance (ICR) cell, herein referred to as the "4X cell", for signal detection at the quadruple frequency multiple was implemented and characterized on a commercial 10 T Fourier transform ICR mass spectrometer (FT-ICR MS). Notably, with the 4X cell operating at a 10 T magnetic field we achieved a 4-fold increase in MS acquisition rate per unit of resolving power for signal detection periods typically employed in FTMS, viz., shorter than 6 s. Effectively, the obtained resolution performance represents the limit of the standard measurement principle with dipolar signal detection and FT signal processing at an equivalent magnetic field of 40 T. In other words, the achieved resolving powers are 4 times higher than those provided by 10 T FT-ICR MS with a standard ICR cell. For example, resolving powers of 170,000 and 70,000 were obtained in magnitude-mode Fourier spectra of 768 and 192 ms apodized transient signals acquired for a singly charged fluorinated phosphazine (m/z 1422) and a 19 fold charged myoglobin (MW 16.9 kDa), respectively. In peptide analysis, the baseline-resolved isotopic fine structures were obtained with as short as 768 ms transients. In intact protein analysis, the average resolving power of 340,000 across the baseline-resolved (13)C isotopic pattern of multiply charged ions of bovine serum albumin was obtained with 1.5 s transients. The dynamic range and the mass measurement accuracy of the 4X cell were found to be comparable to the ones obtained for the standard ICR cell on the same mass spectrometer. Overall, the reported results validate the advantages of signal detection at frequency multiples for increased throughput in FT-ICR MS, essential for numerous applications with time constraints, including proteomics. PMID- 25140617 TI - New approach for the step by step control of magnetic nanostructure functionalization. AB - This paper describes the synthesis, functionalization, and multitechnique analysis of magnetic nanoparticles. The synthetic method involves the covering of a magnetite nucleus by a silica layer and the further functionalization with different fluorophores via a cross-linker molecule. All synthetic intermediates were analyzed by fluorescence spectroscopy and AC magnetic susceptibility. For one of the considered molecules, a further investigation with STEM, EDXS, and DLS has been conducted in order to validate the proposed magnetic results. The comparison between the two techniques is used to ensure a complete characterization of the product confirming the success of the synthesis. By comparing the magnetic and the fluorescence measurements, we also demonstrate the effectiveness of AC susceptibility as a robust and versatile technique to follow the synthesis of complex magnetic nanostructures regardless of the nature of the functionalization. PMID- 25140618 TI - Tremendous effect of the morphology of birnessite-type manganese oxide nanostructures on catalytic activity. AB - The octahedral layered birnessite-type manganese oxide (OL-1) with the morphologies of nanoflowers, nanowires, and nanosheets were prepared and characterized with X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric/differential scanning calorimetry (TG/DSC), Brunnauer-Emmett-Teller (BET), inductively coupled plasma (ICP), and X-ray photoelectron spectroscopy (XPS). The OL-1 nanoflowers possess the highest concentration of oxygen vacancies or Mn(3+), followed by the OL-1 nanowires and nanosheets. The result of catalytic tests shows that the OL-1 nanoflowers exhibit a tremendous enhancement in the catalytic activity for benzene oxidation as compared to the OL-1 nanowires and nanosheets. Compared to the OL-1 nanosheets, the OL-1 nanoflowers demonstrate an enormous decrease (DeltaT(50) = 274 degrees C; DeltaT(90) > 248 degrees C) in reaction temperatures T50 and T90 (corresponding to 50 and 90% benzene conversion, respectively) for benzene oxidation. The origin of the tremendous effect of morphology on the catalytic activity for the nanostructured OL-1 catalysts is experimentally and theoretically studied via CO temperature-programmed reduction (CO-TPR) and density functional theory (DFT) calculation. The tremendous catalytic enhancement of the OL-1 nanoflowers compared to the OL-1 nanowires and nanosheets is attributed to their highest surface area as well as their highest lattice oxygen reactivity due to their higher concentration of oxygen vacancies or Mn(3+), thus tremendously improving the catalytic activity for the benzene oxidation. PMID- 25140619 TI - High photosensitivity few-layered MoSe2 back-gated field-effect phototransistors. AB - In this paper, we report on the fabrication and optoelectronic properties of high sensitive phototransistors based on few-layered MoSe2 back-gated field-effect transistors, with a mobility of 19.7 cm2 V-1 s-1 at room temperature. We obtained an ultrahigh photoresponsivity of 97.1 AW-1 and an external quantum efficiency (EQE) of 22 666% using 532 nm laser excitation at room temperature. The photoresponsivity was improved near the threshold gate voltage; however, the selection of the silicon dioxide as a gate oxide represents a limiting factor in the ultimate performance. Thanks to their high photoresponsivity and external quantum efficiency, the few-layered MoSe2-based devices are promising for photoelectronic applications. PMID- 25140621 TI - Guiding post-treatment decisions in rectal cancer: mrTRG is a practical place to start. PMID- 25140620 TI - Genomewide association studies for 50 agronomic traits in peanut using the 'reference set' comprising 300 genotypes from 48 countries of the semi-arid tropics of the world. AB - Peanut is an important and nutritious agricultural commodity and a livelihood of many small-holder farmers in the semi-arid tropics (SAT) of world which are facing serious production threats. Integration of genomics tools with on-going genetic improvement approaches is expected to facilitate accelerated development of improved cultivars. Therefore, high-resolution genotyping and multiple season phenotyping data for 50 important agronomic, disease and quality traits were generated on the 'reference set' of peanut. This study reports comprehensive analyses of allelic diversity, population structure, linkage disequilibrium (LD) decay and marker-trait association (MTA) in peanut. Distinctness of all the genotypes can be established by using either an unique allele detected by a single SSR or a combination of unique alleles by two or more than two SSR markers. As expected, DArT features (2.0 alleles/locus, 0.125 PIC) showed lower allele frequency and polymorphic information content (PIC) than SSRs (22.21 alleles /locus, 0.715 PIC). Both marker types clearly differentiated the genotypes of diploids from tetraploids. Multi-allelic SSRs identified three sub groups (K = 3) while the LD simulation trend line based on squared-allele frequency correlations (r2) predicted LD decay of 15-20 cM in peanut genome. Detailed analysis identified a total of 524 highly significant MTAs (p value > 2.1 * 10-6) with wide phenotypic variance (PV) range (5.81-90.09%) for 36 traits. These MTAs after validation may be deployed in improving biotic resistance, oil/ seed/ nutritional quality, drought tolerance related traits, and yield/ yield components. PMID- 25140622 TI - Small steps that lead to a giant leap for prostate cancer patients. PMID- 25140623 TI - Pelvic MRI for guiding treatment decisions in rectal cancer. AB - Fluoropyrimidine-based chemoradiation (CRT) is used routinely for locally advanced rectal cancer to shrink the tumor preoperatively, improve lateral surgical clearance at total mesorectal excision, prevent local recurrence, and preserve organ function. In Northern Europe, short-course preoperative radiotherapy (SCPRT) is preferred to achieve locoregional control. However, with recent improvements in the quality of surgery, in magnetic resonance imaging (MRI), and in pathologic reporting, we question whether "routine" CRT or SCPRT should be offered indiscriminately for all patients.MRI is considered the optimal modality for locoregional staging and evaluation of the potential for an involved circumferential resection margin. MRI also provides detailed anatomic information for surgical planning, and may identify poor prognostic features, which influence the way in which the pathologist processes specimens. MRI can predict the likelihood of good/poor tumor response to neoadjuvant CRT and can categorize responders/nonresponders following treatment.Using MRI to define the risk of both local recurrence and metastatic spread allows clinicians to determine which patients might benefit from or safely avoid neoadjuvant treatment. We have arrived at these views after comparing data from published observational studies, results from randomized trials, and outcome analyses of the Norwegian National Cancer Registry. PMID- 25140624 TI - MRI-based treatment decision making for rectal cancer. PMID- 25140625 TI - Squamous cell carcinoma recurring to the great auricular nerve. PMID- 25140626 TI - Expanding androgen- and androgen receptor signaling-directed therapies for castration-resistant prostate cancer. AB - The treatment landscape of castration-resistant prostate cancer (CRPC) has been dramatically changed over the past years with the approval of several new drugs for clinical use. These include androgen axis-targeted therapy and novel drugs with different mechanisms of action, including immunotherapy (sipuleucel-T), radiopharmaceuticals (radium-223), and chemotherapy (cabazitaxel). Based on the growing knowledge that the main driver for patients progressing on standard androgen deprivation therapy is persistent activation of the androgen receptor (AR) signaling axis, new drugs were developed and demonstrated significant efficacy in recent clinical trials, leading to the approval of abiraterone and enzalutamide in several countries. In this article, we review the most recent advances in AR-directed therapies for CRPC, promising new agents under development, cross-resistance, and mechanisms of resistance for the new generation AR-targeted agents. PMID- 25140627 TI - Targeting the androgen receptor signaling axis to reduce testosterone levels in prostate cancer: how low should we go? PMID- 25140628 TI - The urology perspective on expanding androgen-targeted treatments for men with castration-resistant prostate cancer. PMID- 25140629 TI - ACR Appropriateness Criteria(r) nonsurgical treatment for locally advanced non small-cell lung cancer: good performance status/definitive intent. AB - Concurrent chemotherapy/radiotherapy has been considered the standard treatment for patients with a good performance status and inoperable stage III non-small cell lung cancer (NSCLC). Three-dimensional chemoradiation therapy and intensity modulated radiation therapy have been reported to reduce toxicity and allow a dose escalation to 70 Gy and beyond. However, the Radiation Therapy Oncology Group 0617 trial recently showed that dose escalation from 60 Gy to 74 Gy with concurrent chemotherapy in stage III NSCLC was associated with higher toxicity and worse survival. A "one size fits all" treatment approach may need to be changed and adapted to each patient's particular disease and unique biologic/anatomic features, as well as the most appropriate radiotherapy modalities for that patient. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application, by the panel, of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures. In instances in which evidence is lacking or not definitive, expert opinion may be used as the basis for recommending imaging or treatment. PMID- 25140632 TI - An ultrasonic contactless sensor for breathing monitoring. AB - The monitoring of human breathing activity during a long period has multiple fundamental applications in medicine. In breathing sleep disorders such as apnea, the diagnosis is based on events during which the person stops breathing for several periods during sleep. In polysomnography, the standard for sleep disordered breathing analysis, chest movement and airflow are used to monitor the respiratory activity. However, this method has serious drawbacks. Indeed, as the subject should sleep overnight in a laboratory and because of sensors being in direct contact with him, artifacts modifying sleep quality are often observed. This work investigates an analysis of the viability of an ultrasonic device to quantify the breathing activity, without contact and without any perception by the subject. Based on a low power ultrasonic active source and transducer, the device measures the frequency shift produced by the velocity difference between the exhaled air flow and the ambient environment, i.e., the Doppler effect. After acquisition and digitization, a specific signal processing is applied to separate the effects of breath from those due to subject movements from the Doppler signal. The distance between the source and the sensor, about 50 cm, and the use of ultrasound frequency well above audible frequencies, 40 kHz, allow monitoring the breathing activity without any perception by the subject, and therefore without any modification of the sleep quality which is very important for sleep disorders diagnostic applications. This work is patented (patent pending 2013-7 31 number FR.13/57569). PMID- 25140631 TI - Intra-and-inter species biomass prediction in a plantation forest: testing the utility of high spatial resolution spaceborne multispectral RapidEye sensor and advanced machine learning algorithms. AB - The quantification of aboveground biomass using remote sensing is critical for better understanding the role of forests in carbon sequestration and for informed sustainable management. Although remote sensing techniques have been proven useful in assessing forest biomass in general, more is required to investigate their capabilities in predicting intra-and-inter species biomass which are mainly characterised by non-linear relationships. In this study, we tested two machine learning algorithms, Stochastic Gradient Boosting (SGB) and Random Forest (RF) regression trees to predict intra-and-inter species biomass using high resolution RapidEye reflectance bands as well as the derived vegetation indices in a commercial plantation. The results showed that the SGB algorithm yielded the best performance for intra-and-inter species biomass prediction; using all the predictor variables as well as based on the most important selected variables. For example using the most important variables the algorithm produced an R2 of 0.80 and RMSE of 16.93 t.ha-1 for E. grandis; R2 of 0.79, RMSE of 17.27 t.ha-1 for P. taeda and R2 of 0.61, RMSE of 43.39 t.ha-1 for the combined species data sets. Comparatively, RF yielded plausible results only for E. dunii (R2 of 0.79; RMSE of 7.18 t.ha-1). We demonstrated that although the two statistical methods were able to predict biomass accurately, RF produced weaker results as compared to SGB when applied to combined species dataset. The result underscores the relevance of stochastic models in predicting biomass drawn from different species and genera using the new generation high resolution RapidEye sensor with strategically positioned bands. PMID- 25140630 TI - Expression of autophagy-related proteins according to androgen receptor and HER-2 status in estrogen receptor-negative breast cancer. AB - PURPOSE: The purpose of this study was to investigate the expression of autophagy related proteins in relation to androgen receptor (AR) status in estrogen receptor (ER)-negative breast cancers. METHODS: We extracted 334 ER-negative breast cancer samples to construct tissue microarrays (TMAs), which were immunohistochemically stained for autophagy-related proteins (beclin-1, LC3A, LC3B, p62) and for AR and HER-2. RESULTS: There were 127 AR-positive cases and 207 AR-negative cases, and 140 HER-2-positive cases and 194 HER-2 negative cases. The AR-negative group was associated with tumoral LC3A expression (P<0.001), while the AR-positive group was associated with tumoral BNIP3 expression (P<0.001). Tumoral LC3A was most highly expressed in the AR-negative and HER-2 negative group, while stromal LC3A showed the highest expression in the AR negative and HER-2-positive group. Tumoral BNIP3 and stromal BNIP3 were highest in the AR-positive and HER-2-negative group. In the AR-positive and HER-2 negative group, stromal p62 positivity was an independent factor that was statistically significant in its association with shorter disease-free survival (DFS) (Hazard ratio: 10.21, 95% CI: 1.130-92.31, P = 0.039). Shorter DFS was associated with tumoral LC3A positivity (Hazard ratio: 10.28, 95% CI: 2.068 51.19, P = 0.004) in the AR-negative and HER-2-positive group. CONCLUSION: In ER negative breast cancers, AR status was associated with expression of different types of autophagy-related proteins. Tumoral LC3A was most highly expressed in AR negative breast cancers, while tumor BNIP3 was highest in AR-positive breast cancers. PMID- 25140633 TI - Directional navigation improves opportunistic communication for emergencies. AB - We present a novel direction based shortest path search algorithm to guide evacuees during an emergency. It uses opportunistic communications (oppcomms) with low-cost wearable mobile nodes that can exchange packets at close range of a few to some tens of meters without help of an infrastructure. The algorithm seeks the shortest path to exits which are safest with regard to a hazard, and is integrated into an autonomous Emergency Support System (ESS) to guide evacuees in a built environment. The algorithm proposed that ESSs are evaluated with the DBES (Distributed Building Evacuation Simulator) by simulating a shopping centre where fire is spreading. The results show that the directional path finding algorithm can offer significant improvements for the evacuees. PMID- 25140634 TI - Rapid, single-molecule assays in nano/micro-fluidic chips with arrays of closely spaced parallel channels fabricated by femtosecond laser machining. AB - Cost-effective pharmaceutical drug discovery depends on increasing assay throughput while reducing reagent needs. To this end, we are developing an ultrasensitive, fluorescence-based platform that incorporates a nano/micro fluidic chip with an array of closely spaced channels for parallelized optical readout of single-molecule assays. Here we describe the use of direct femtosecond laser machining to fabricate several hundred closely spaced channels on the surfaces of fused silica substrates. The channels are sealed by bonding to a microscope cover slip spin-coated with a thin film of poly(dimethylsiloxane). Single-molecule detection experiments are conducted using a custom-built, wide field microscope. The array of channels is epi-illuminated by a line-generating red diode laser, resulting in a line focus just a few microns thick across a 500 micron field of view. A dilute aqueous solution of fluorescently labeled biomolecules is loaded into the device and fluorescence is detected with an electron-multiplying CCD camera, allowing acquisition rates up to 7 kHz for each microchannel. Matched digital filtering based on experimental parameters is used to perform an initial, rapid assessment of detected fluorescence. More detailed analysis is obtained through fluorescence correlation spectroscopy. Simulated fluorescence data is shown to agree well with experimental values. PMID- 25140635 TI - A Kalman filter-based short baseline RTK algorithm for single-frequency combination of GPS and BDS. AB - The emerging Global Navigation Satellite Systems (GNSS) including the BeiDou Navigation Satellite System (BDS) offer more visible satellites for positioning users. To employ those new satellites in a real-time kinematic (RTK) algorithm to enhance positioning precision and availability, a data processing model for the dual constellation of GPS and BDS is proposed and analyzed. A Kalman filter-based algorithm is developed to estimate the float ambiguities for short baseline scenarios. The entire work process of the high-precision algorithm based on the proposed model is deeply investigated in detail. The model is validated with real GPS and BDS data recorded from one zero and two short baseline experiments. Results show that the proposed algorithm can generate fixed baseline output with the same precision level as that of either a single GPS or BDS RTK algorithm. The significantly improved fixed rate and time to first fix of the proposed method demonstrates a better availability and effectiveness on processing multi-GNSSs. PMID- 25140636 TI - Estimation of spatial-temporal gait parameters using a low-cost ultrasonic motion analysis system. AB - In this paper, a low-cost motion analysis system using a wireless ultrasonic sensor network is proposed and investigated. A methodology has been developed to extract spatial-temporal gait parameters including stride length, stride duration, stride velocity, stride cadence, and stride symmetry from 3D foot displacements estimated by the combination of spherical positioning technique and unscented Kalman filter. The performance of this system is validated against a camera-based system in the laboratory with 10 healthy volunteers. Numerical results show the feasibility of the proposed system with average error of 2.7% for all the estimated gait parameters. The influence of walking speed on the measurement accuracy of proposed system is also evaluated. Statistical analysis demonstrates its capability of being used as a gait assessment tool for some medical applications. PMID- 25140637 TI - Pyridylenevinylene based Cu(2+)-specific, injectable metallo(hydro)gel: thixotropy and nanoscale metal-organic particles. AB - A Cu(2+)-selective metallo(hydro)gelation of a p-pyridyl ended oligo phenylenevinylene system is reported over its respective meta- and ortho regioisomers. The metallogel formed via the self-assembly of the nanoscale-metal organic particles is injectable and also shows multi-stimuli responsiveness, including thixotropy. PMID- 25140638 TI - Experience of nurses caring for child with hematopoietic stem cell transplantation in general pediatric ward: a descriptive phenomenological approach. AB - BACKGROUND: Most studies on hematopoietic stem cell transplantation (HSCT) have focused on patients, survivors, or their family members, such as siblings and parents. Little attention has been paid to nurses caring for HSCT pediatric patients and in particular in a Taiwanese context. OBJECTIVE: The objective of this study was to explore nurses' lived experience caring for HSCT children in isolation within a general pediatric ward. METHOD: A Husserlian phenomenological approach informed the exploration of the meaning and essence of the nurses' caring experience. Data were collected using semistructured interviews. RESULTS: Twelve nurses were interviewed. Analysis of interviews yielded 3 main themes: being worried about ruining transplantation success, feeling loss of control in handling suffering, and reflecting upon the value of HSCT. CONCLUSIONS: Nurses felt the stress of caring for HSCT children because of the heavy workload and the pressure of responsibility. Witnessing the suffering of patients/families was particularly stressful. However, nurses were helped to overcome this stress by looking at the value and meaning of HSCT. IMPLICATIONS FOR PRACTICE: Nurses need practical support from nursing leaders in terms of carefully organizing patient care, controlling the nurse-to-patient ratio, and offering a safe work environment by providing systematic formal training on HSCT and receiving proper supervision. Understanding and learning are gained from nurses who are able to seek meaning from HSCT through appreciating every caregiving effort and through valuing how their nursing role contributes to the quality of patients' care. PMID- 25140640 TI - Psychometric properties of a Chinese version of the Colorectal Cancer Perceptions Scale in a sample of older Chinese people. AB - BACKGROUND: Older adults are more susceptible to colorectal cancer (CRC). Psychosocial constructs in the Health Belief Model are targets for interventional studies. No tool to measure these beliefs of older Chinese people has been validated. OBJECTIVE: The present study aimed to examine the preliminary psychometric properties of the Chinese version of the Colorectal Cancer Perceptions Scale (CRCPS). METHODS: The CRCPS was translated to Chinese language, validated by an expert panel, and tested. Interviewer-administered surveys were carried out with a convenience sample of 219 community-dwelling Chinese adults 60 years or older and were included in the analysis. RESULTS: Six factors were retained, with items on susceptibility and benefits remaining as designed, whereas those on severity formed 2 factors, labeled severity-fear and severity life impact, and those on barriers again formed 2 factors, labeled psychological barriers and knowledge barriers. Cronbach's alpha values ranged from .74 to .88, and test-retest reliability correlations ranged from .38 for psychological barriers to .69 for knowledge barriers. Respondents who had undergone CRC screening had significantly lower mean scores on severity-fear, severity-life impact, psychological barriers, and knowledge barriers compared with those who had not. CONCLUSIONS: The results provide preliminary support for the reliability and validity of the Chinese version of the CRCPS. Further psychometric testing is recommended. IMPLICATIONS FOR PRACTICE: The survey provides a useful tool to assess CRC health beliefs, which interventions should address to improve screening rates among older Chinese adults. PMID- 25140639 TI - Physician and nurse beliefs of phase 1 trials in pediatric oncology. AB - BACKGROUND: In order to improve the survival of children with cancer, novel therapies must be identified. Promising agents are tested in phase 1 trials in order to identify appropriate dosing and describe toxicity in children. The identification and referral of candidate patients for phase 1 trials rely heavily on medical providers who must balance their own perceptions of phase 1 trials with the desires and willingness of the patient and his/her family. OBJECTIVE: The goal of the present study was to evaluate and compare physician and nurse perceptions regarding the beliefs, expectations, and perceived benefits of phase 1 clinical trials. METHODS: A survey consisting of 21 questions was sent to 419 physicians and nurses practicing pediatric oncology at 30 different institutions. With the exception of 10 demographic questions, items were either rank ordered or rated on 5-point Likert scales. RESULTS: Ninety-four physicians and 122 nurses completed the online survey. Physicians and nurses differed in their knowledge of the goals and medical effects of phase 1 clinical trials. CONCLUSIONS: Physicians and nurses hold positive beliefs regarding phase 1 clinical trials and support their role in the treatment of children with cancer. Education is necessary to increase nurses' knowledge of the goals and outcomes. IMPLICATIONS FOR PRACTICE: These findings suggest that continued education of nurses as well as physicians about the goals, execution, and monitoring of phase 1 therapy would be worthwhile. PMID- 25140642 TI - [The hazing and the ethical responsibility of the future doctors]. PMID- 25140643 TI - [Value of tissue biomarkers and pet-ct in the prognosis of head and neck cancer: review of diagnostic and therapeutic paradigm]. PMID- 25140641 TI - Enhancement of biological reactions on cell surfaces via macromolecular crowding. AB - The reaction of macromolecules such as enzymes and antibodies with cell surfaces is often an inefficient process, requiring large amounts of expensive reagent. Here we report a general method based on macromolecular crowding with a range of neutral polymers to enhance such reactions, using red blood cells (RBCs) as a model system. Rates of conversion of type A and B red blood cells to universal O type by removal of antigenic carbohydrates with selective glycosidases are increased up to 400-fold in the presence of crowders. Similar enhancements are seen for antibody binding. We further explore the factors underlying these enhancements using confocal microscopy and fluorescent recovery after bleaching (FRAP) techniques with various fluorescent protein fusion partners. Increased cell-surface concentration due to volume exclusion, along with two-dimensionally confined diffusion of enzymes close to the cell surface, appear to be the major contributing factors. PMID- 25140645 TI - Impact of bariatric surgery on depression and anxiety symptons, bulimic behaviors and quality of life. AB - OBJECTIVE: To assess psychiatric symptoms, substance use, quality of life and eating behavior of patients undergoing bariatric surgery before and after the procedure. METHODS: We conducted a prospective longitudinal study of 32 women undergoing bariatric surgery. To obtain data, the patients answered specific, self-administered questionnaires. RESULTS: We observed a reduction in depressive and anxious symptoms and also in bulimic behavior, as well as an improved quality of life in the physical, psychological and environmental domains. There was also a decrease in use of antidepressants and appetite suppressants, but the surgery was not a cessation factor in smoking and / or alcoholism. CONCLUSION: a decrease in psychiatric symptoms was observed after bariatric surgery, as well as the reduction in the use of psychoactive substances. In addition, there was an improvement in quality of life after surgical treatment of obesity. PMID- 25140644 TI - The cost of excessive postoperative use of antimicrobials: the context of a public hospital. AB - OBJECTIVE: To evaluate the improper use of antimicrobials during the postoperative period and its economic impact. METHODS: We conducted a prospective cohort study by collecting data from medical records of 237 patients operated on between 01/11/08 and 31/12/08. RESULTS: from the 237 patients with the information collected, 217 (91.56%) received antimicrobials. During the postoperative period, 125 (57.7%) patients received more than two antimicrobials. On average, 1.7 +/- 0.6 antimicrobials were prescribed to patients, the most commonly prescribed antibiotic being cephalothin, in 41.5% (154) of cases. The direct cost of antimicrobial therapy accounted for 63.78% of all drug therapy, this large percentage being attributed in part to the extended antimicrobial prophylaxis. In the case of clean operations, where there was a mean duration of 5.2 days of antibiotics, antimicrobials represented 44.3% of the total therapy cost. CONCLUSION: The data illustrate the impact of overuse of antimicrobials, with questionable indications, creating situations that compromise patient safety and increasing costs in the assessed hospital. PMID- 25140646 TI - Implementation of a perioperative management protocol for patients undergoing orthopedic surgery. AB - OBJECTIVE: To evaluate the initial results after the implementation of perioperative protocol in patients over 60 years of age undergoing surgical treatment for femur fractures. METHODS: We conducted a prospective study of patients older than 60 years who were hospitalized with femur fracture. They were operated under spinal anesthesia and analgesia by lumbar plexus blockade. Data evaluation was performed before arrival in the operating room during surgery, in the post-anesthesia recovery room and in the ward the next morning of the operation. RESULTS: 105 patients underwent various types of surgical corrections of the femur. The hospital stay ranged from three to 86 days. Fasting ranged from 9h15min to 19h30mn. Hypotension occurred in 5.7%. The duration of motor blockade ranged from 1h45min to 5h30imn. Maltodextrin feeding ranged from 50min to 3h45min and the time spent in the post-anesthetic care unit ranged from 50 minutes to 4 hours. Onset of oral intake in the ward ranged from 4hto 8h15min. The duration of anesthesia ranged from 14 to 33 hours. No patient required a urinary catheter, nor was transferred to the ICU. All patients were able to be discharged on the first postoperative day. CONCLUSION: The use of a protocol to accelerate the postoperative period may reduce the fasting time, length of hospital stay and provide faster i discharge n elderly patients with femur fractures. PMID- 25140647 TI - Association between peripheral arterial disease and C-reactive protein in the Japanese-Brazilian population. AB - OBJECTIVE: To evaluate the relationship between peripheral arterial disease and elevated levels of C-reactive protein in the Japanese-Brazilian population of high cardiovascular risk. METHODS: We conducted a cross-sectional study derived from a population-based study on the prevalence of diabetes and associated diseases in the Japanese-Brazilian population. One thousand, three hundred and thirty individuals aged e" 30 underwent clinical and laboratory examination, including measurement of ultrasensitive C-reactive protein. The diagnosis of peripheral arterial disease was performed by calculating the ankle-brachial index. We considered with peripheral arterial disease patients who had ankle brachial index d" 0.9. After applying the exclusion criteria, 1,038 subjects completed the study. RESULTS: The mean age of the population was 56.8 years; 46% were male. The prevalence of peripheral arterial disease was 21%, with no difference between genders. Data analysis showed no association between peripheral arterial disease and ultrasensitive C-reactive protein. Patients with ankle-brachial index d" 0.70 showed higher values of ultrasensitive C-reactive protein and worse cardiometabolic profile. We found a positive independent association of peripheral arterial disease with hypertension and smoking. CONCLUSION: The association between low levels of ankle-brachial index and elevated levels of ultrasensitive C-reactive protein may suggest a relationship of gravity, aiding in the mapping of high-risk patients. PMID- 25140648 TI - Haematological and biochemical characteristics of the splenic effluent blood in schistosomal patients undergoing splenectomy. AB - OBJECTIVE: To assess hematological and biochemical features of splenic effluent blood and their influence on the rise of hematological values after splenectomy. METHODS: we studied 20 patients undergoing surgical treatment for schistosomatic portal hypertension. We collected blood samples for CBC, coagulation, bilirubin and albumin in the splenic vein (perioperative) and peripheral blood (immediately pre and postoperative periods). RESULTS: the splenic blood showed higher values of red blood cells, hemoglobin, hematocrit, platelet count, total leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils, as well as reduction of laboratory coagulation parameters in relation to peripheral blood collected preoperatively. In the postoperative peripheral blood there was an increase in the overall leukocytes and in their neutrophil component, and decreased levels of basophils, eosinophils and lymphocytes. The other postoperative variables of complete blood count and coagulation tests were not different compared with the splenic blood. The albumin values were lower postoperatively when compared to preoperative and splenic blood. There were higher values of direct bilirubin in the postoperative period when compared with the preoperative and splenic blood. Postoperative indirect bilirubin was lower compared to its value in the splenic blood. CONCLUSION: hematological and biochemical values of splenic effluent blood are higher than those found in peripheral blood in the presence of schistosomal splenomegaly. However, the splenic blood effluent is not sufficient to raise the blood levels found after splenectomy. PMID- 25140649 TI - Standardization of pulmonary ventilation technique using volume-controlled ventilators in rats with congenital diaphragmatic hernia. AB - OBJECTIVE: To standardize a technique for ventilating rat fetuses with Congenital Diaphragmatic Hernia (CDH) using a volume-controlled ventilator. METHODS: Pregnant rats were divided into the following groups: a) control (C); b) exposed to nitrofen with CDH (CDH); and c) exposed to nitrofen without CDH (N-). Fetuses of the three groups were randomly divided into the subgroups ventilated (V) and non-ventilated (N-V). Fetuses were collected on day 21.5 of gestation, weighed and ventilated for 30 minutes using a volume-controlled ventilator. Then the lungs were collected for histological study. We evaluated: body weight (BW), total lung weight (TLW), left lung weight (LLW), ratios TLW / BW and LLW / BW, morphological histology of the airways and causes of failures of ventilation. RESULTS: BW, TLW, LLW, TLW / BW and LLW / BW were higher in C compared with N- (p <0.05) and CDH (p <0.05), but no differences were found between the subgroups V and N-V (p> 0.05). The morphology of the pulmonary airways showed hypoplasia in groups N- and CDH, with no difference between V and N-V (p <0.05). The C and N- groups could be successfully ventilated using a tidal volume of 75 il, but the failure of ventilation in the CDH group decreased only when ventilated with 50 il. CONCLUSION: Volume ventilation is possible in rats with CDH for a short period and does not alter fetal or lung morphology. PMID- 25140650 TI - Modified method for bronchial suture by Ramirez Gama compared to separate stitches suture: experimental study. AB - OBJECTIVE: To experimentally compare two classic techniques described for manual suture of the bronchial stump. METHODS: We used organs of pigs, with isolated trachea and lungs, preserved by refrigeration. We dissected 30 bronchi, which were divided into three groups of ten bronchi each, of 3mm, 5mm, and 7mm, respectively. In each, we performed the suture with simple, separated, extramucosal stitches in five other bronchi, and the technique proposed by Ramirez and modified by Santos et al in the other five. Once the sutures were finished, the anastomoses were tested using compressed air ventilation, applying an endotracheal pressure of 20mmHg. RESULTS: the Ramirez Gama suture was more effective in the bronchi of 3, 5 and 7 mm, and there was no air leak even after subjecting them to a tracheal pressure of 20mmHg. The simple interrupted sutures were less effective, with extravasation in six of the 15 tested bronchi, especially in the angles of the sutures. These figures were not significant (p = 0.08). CONCLUSION: manual sutures of the bronchial stumps were more effective when the modified Ramirez Gama suture was used in the caliber bronchi arms when tested with increased endotracheal pressure. PMID- 25140652 TI - Comparison between electrocautery and fibrin selant after hepatectomy in rats. AB - OBJECTIVE: To compare between electrocautery and fibrin sealant hemostasis in rats after partial hepatectomy. METHODS: we used 24 Wistar rats, which were submitted to 30% hepatic resection, divided into two groups of 12 animals each: Group Electrocautery and Group Tachosil(r). These animals were evaluated after three and 14 days. We assessed the presence of complications, laboratory tests and histological exam of the recovered liver. RESULTS: the presence of abscess was more prevalent in the electrocautery group. The observed adhesions were more pronounced in the electrocautery group, both in frequency and in intensity, after three and 14 days. There were no deaths in either group. As for laboratory analysis, after three days the hematocrit was lower in the TachoSil(r) Group. The elevation of AST and ALT were more pronounced in the electrocautery group (p = 0.002 and p = 0.004) in three days. Histological analysis of specimens collected on the third day after surgery showed similar results in both groups for the presence of polymorphonuclear cells, whereas mononuclear was more evident in the TachoSil(r) group. We also observed that angiogenesis, although present in both groups, was more pronounced in the TachoSil(r) group (p = 0.030). However, on the 14th day angiogenesis was more pronounced in the electrocautery group, but without statistical significance. CONCLUSION: hemostasis achieved by the groups was similar; however, the use of electrocautery was associated with infections, adhesions at higher grades and elevated liver enzymes. PMID- 25140651 TI - Effect of the celexoxib in microscopic changes of the esophageal mucosal of rats induced by esofagojejunostomy. AB - OBJECTIVE: To evaluate the protective effect of celecoxib in the esophageal mucosa in rats undergoing esofagojejunostomy. METHODS: Sixty male Wistar rats from the vivarium of the University of Health Sciences of Alagoas were used for the experiment. The animals were divided into four groups: Group I, 15 rats undergoing esofagojejunostomy with the use of celecoxib postoperatively; Group II, 15 rats undergoing esofagojejunostomy without the use of celecoxib; Group III, 15 rats undergoing celiotomy with bowel manipulation; and Group IV, 15 rats without surgery and using celecoxib. The observation period was 90 days. After the death of the animals, the distal segment of the esophagus was resected and sent for microscopic analysis. RESULTS: esofagojejunostomy caused macroscopic and microscopic esophagitis. Esophagitis was equal in both groups I and II. In groups III and IV esophageal lesions were not developed. CONCLUSIONS: celecoxib had neither protective nor inducing effect on esophagitis, but had a protective effect on dysplasia of the animals of group I. PMID- 25140654 TI - Surgical treatment of cleft lip. AB - We performed a systematic review of the literature on the surgical treatment of cleft lip, emphasizing the prevalence, complications associated with the treatment and the points of disagreement between authors. We conducted a literature cross-sectional search that analyzed publications in books, articles and on the databases SciELO - Scientific Electronic Library Online, PubMed, of the National Center for Biotechnology Information. We conclude that: 1) the severity of the cleft will indicate the technique presenting more advantages; 2) the different approaches indicate that there is no consensus on the optimal technique; and 3) the surgeon experience contributes to choosing the best option. PMID- 25140653 TI - Sirolimus influence on hepatectomy-induced liver regeneration in rats. AB - OBJECTIVE: To evaluate the influence of sirolimus on liver regeneration triggered by resection of 70% of the liver of adult rats. METHODS: we used 40 Wistar rats randomly divided into two groups (study and control), each group was divided into two equal subgroups according to the day of death (24 hours and seven days). Sirolimus was administered at a dose of 1mg/kg in the study group and the control group was given 1 ml of saline. The solutions were administered daily since three days before hepatectomy till the rats death to removal of the regenerated liver, conducted in 24 hours or 7 days after hepatectomy. Liver regeneration was measured by the KWON formula, by the number of mitotic figures (hematoxylin-eosin staining) and by the immunohistochemical markers PCNA and Ki-67. RESULTS: there was a statistically significant difference between the 24h and the 7d groups. When comparing the study and control groups in the same period, there was a statistically significant variation only for Ki-67, in which there were increased numbers of hepatocytes in cell multiplication in the 7d study group compared with the 7d control group (p = 0.04). CONCLUSION: there was no negative influence of sirolimus in liver regeneration and there was a positive partial effect at immunohistochemistry with Ki-67. PMID- 25140655 TI - Four-arm single docking full robotic surgery for low rectal cancer: technique standardization. AB - The authors present the four-arm single docking full robotic surgery to treat low rectal cancer. The eight main operative steps are: 1- patient positioning; 2- trocars set-up and robot docking; 3- sigmoid colon, left colon and splenic flexure mobilization (lateral-to-medial approach); 4-Inferior mesenteric artery and vein ligation (medial-to-lateral approach); 5- total mesorectum excision and preservation of hypogastric and pelvic autonomic nerves (sacral dissection, lateral dissection, pelvic dissection); 6- division of the rectum using an endo roticulator stapler for the laparoscopic performance of a double-stapled coloanal anastomosis (type I tumor); 7- intersphincteric resection, extraction of the specimen through the anus and lateral-to-end hand sewn coloanal anastomosis (type II tumor); 8- cylindric abdominoperineal resection, with transabdominal section of the levator muscles (type IV tumor). The techniques employed were safe and have presented low rates of complication and no mortality. PMID- 25140656 TI - [Is professional recognition in plastic surgery related to activity in research]. AB - OBJECTIVE: To evaluate the relation of medical research, with the participation of prominent plastic surgeon in Congress. METHODS: We reviewed the scientific programs of the last 3 Brazilian Congress of Surgery, were selected 21 Brazilian plastic surgeons invited to serve as panelists or speakers in roundtable sessions in the last 3 congresses (Group 1). We randomly selected and paired by other members (associates) of the Brazilian Society of Plastic Surgery, with no participation in congress as speaker (Group 2). We conducted a search for articles published in journals indexed in Medline, Lilacs and SciELO for all doctors selected during the entire academic career and the last 5 years from March 2007 until March 2012. We assessed the research activity through the simple counting of the number of publications in indexed journals for each professional. The number of publications groups was compared. RESULTS: articles produced throughout career: Group 1- 639 articles (average of 30.42 items each). Group 2- 79 articles (mean 3.95 articles each). Difference between medias: p <0.001. CONCLUSION: The results demonstrate that the Brazilian Society of Plastic Surgery seeking professionals with a greater number of publications and journals of higher impact. This approach encourages new members to pursue a higher qualification, and give security to congressmen, they can rely on the existence of a technical criterion in the choice of speakers. PMID- 25140657 TI - Is there a role for pyloric exclusion after severe duodenal trauma? AB - Duodenal trauma is an infrequent injury, but linked to high morbidity and mortality. Surgical management of duodenal injuries is dictated by: patient's hemodynamic status, injury severity, time of diagnosis, and presence of concomitant injuries. Even though most cases can be treated with primary repair, some experts advocate adjuvant procedures. Pyloric exclusion (PE) has emerged as an ancillary method to protect suture repair in more complex injuries. However, the effectiveness of this procedure is debatable. The "Evidence Based Telemedicine - Trauma & Acute Care Surgery" (EBT-TACS) Journal Club performed a critical appraisal of the literature and selected three relevant publications on the indications for PE in duodenal trauma. The first study retrospectively compared 14 cases of duodenal injuries greater than grade II treated by PE, with 15 cases repaired primarily, all of which penetrating. Results showed that PE did not improve outcome. The second study, also retrospective, compared primary repair (34 cases) with PE (16 cases) in blunt and penetrating grade > II duodenal injuries. The authors concluded that PE was not necessary in all cases. The third was a literature review on the management of challenging duodenal traumas. The author of that study concluded that PE is indicated for anastomotic leak management after gastrojejunostomies. In conclusion, the choice of the surgical procedure to treat duodenal injuries should be individualized. Moreover, there is insufficient high quality scientific evidence to support the abandonment of PE in severe duodenal injuries with extensive tissue loss. PMID- 25140659 TI - Multinucleate cell angiohistiocytoma: clinicopathological correlation of 142 cases with insights into etiology and pathogenesis. AB - INTRODUCTION: Multinucleate cell angiohistiocytoma (MCAH) is a peculiar dermatopathological entity described as asymptomatic grouped red-to-violaceous papules, developing over weeks to months without spontaneous regression. The histopathological findings comprise bizarre basophilic multinucleated cells (MC), small vessel inflammation, mild dermal fibrosis, and a sparse lymphohistiocytic infiltrate. AIMS AND METHODS: This study aimed to collate and analyze the clinical, histological, and immunohistochemical characteristics of all reported cases of MCAH from the international literature, and the presence or absence of concurrent chronic inflammatory or neoplastic phenomena to investigate any potential clinicopathological correlations, which may hint at the underlying pathophysiology of this condition. A systematic review of the literature was undertaken with information collected by a predeveloped pro forma. New case reports were also sourced from patient records at the Skin and Cancer Foundation Australia Database. RESULTS: A total of 142 cases of MCAH were collated, including 8 new case reports. The average age of onset was 50.1 years, with 79% of all individuals being female. The most commonly affected areas were the hands (30%) and face (29%). Univariate analysis revealed a positive association between lesion size and MC staining for CD68 (R = 0.488; P = 0.004), and an inverse relationship between size and endothelial staining for CD34 (R = -0.530; P = 0.012). Multiple lesions were significantly associated with an inverse relationship to MC staining of CD68 (R = -0.519; P = 0.002). Moderate correlations were seen between specific sites of vascularity and sites in which MCs were identified (R = 0.734-0.741; P < 0.001), and dermal fibrosis was associated with an increased number of MCs (R = 0.522; P = 0.002) and decreased multinucleate cell immunohistochemical staining (R = -0.655; P = 0.003). An association was found between patients with chronic inflammatory conditions and endothelial staining for CD68 (R = 0.671; P = 0.012), and an inverse relationship with MC staining for factor XIIIa (-0.481; P < 0.001). No statistically significant relationships between neoplasia and MCAH were found. DISCUSSION AND CONCLUSIONS: From the data examined, we hypothesize that although this condition may be inflammatory and vascular in initial origin, fibrosis and atrophy play a vital role in the pathogenesis, particularly regarding the progression to multiple lesions. A detailed hypothesis is described that may be amenable to more detailed investigations. Limitations in this study include the heterogeneity of results analyzed across case reports; however, our conclusions match those developed through the analysis of our case series. These hypotheses and proposals provide an experimental basis for further research into the pathogenesis and mechanisms underlying MCAH. PMID- 25140660 TI - A unique case of a cutaneous lesion resembling mammary analog secretory carcinoma: a case report and review of the literature. AB - Mammary analog secretory carcinoma (MASC) is a rare type of salivary gland tumor named for its morphological and genetic similarity to secretory carcinoma of the breast. These tumors are most often found in the parotid gland but have been described in several other mucosal locations of the head and neck. In this case report, a cutaneous lesion most closely resembling MASC was found in a neck mass of a 64-year-old male patient without evidence of a primary salivary gland or oral tumor. The lesion was excised, and the patient remains disease free to date. This case depicts a rare tumor in the skin most closely mimicking MASC and brings additional awareness to dermatopathologists of this tumor. PMID- 25140658 TI - Retrieval intention modulates the effects of directed forgetting instructions on recollection. AB - The neurocognitive basis of memory retrieval is often examined by investigating brain potential old/new effects, which are differences in brain activity between successfully remembered repeated stimuli and correctly rejected new stimuli in a recognition test. In this study, we combined analyses of old/new effects for words with an item-method directed-forgetting manipulation in order to isolate differences between the retrieval processes elicited by words that participants were initially instructed to commit to memory and those that participants were initially instructed to forget. We compared old/new effects elicited by to-be forgotten (TBF) words with those elicited by to-be-remembered (TBR) words in both an explicit-memory test (a recognition test) and an implicit-memory test (a lexical-decision test). Behavioral results showed clear directed forgetting effects in the recognition test, but not in the lexical decision test. Mirroring the behavioral findings, analyses of brain potentials showed evidence of directed forgetting only in the recognition test. In this test, potentials from 450-650 ms (P600 old/new effects) were more positive for TBR relative to TBF words. By contrast, P600 effects evident during the lexical-decision test did not differ in magnitude between TBR and TBF items. When taken in the context of prior studies that have linked similar parietal old/new effects to the recollection of episodic information, these data suggest that directed-forgetting effects manifest primarily in greater episodic retrieval by TBR than TBF items, and that retrieval intention may be important for these directed-forgetting effects to occur. PMID- 25140661 TI - Multiple distinct T-cell clones in folliculotropic mycosis fungoides. AB - Multiple distinct T-cell clones have been demonstrated in a subset of mycosis fungoides (MF), but have so far not been documented in folliculotropic MF, a clinical and histological variant of MF. We analyzed T-cell receptor (TCR) gene rearrangements in 8 patients with folliculotropic MF with multiple biopsies (range, 2-5) taken during the course of disease. Two patients had disease stage IA-IIA, 5 stage IIB-IVA, whereas data were not available for 1 patient. TCR beta and gamma gene rearrangements were analyzed according to the BIOMED-2 PCR protocol. Multiple clonal TCR gene rearrangements indicating more than 1 T-cell clone were found in 5 patients. Although the number of patients is small, the finding of multiple distinct T-cell clones in 5 out of 8 patients suggests that chronic T-cell stimulation contributes to the development of folliculotropic MF. PMID- 25140662 TI - Granuloma Annulare Mimicking Sarcoidosis: Report of Patient With Localized Granuloma Annulare Whose Skin Lesions Show 3 Clinical Morphologies and 2 Histology Patterns. AB - Granuloma annulare, a benign dermatosis of undetermined etiology, typically presents in a localized or generalized form. It has 3 distinctive histologic patterns: an infiltrative (interstitial) pattern, a palisading granuloma pattern, and an epithelioid nodule (sarcoidal granuloma) pattern. A man whose granuloma annulare skin lesions mimicked sarcoidosis is described. His localized granuloma annulare presented with a total of 3 lesions that each had a distinctive clinical morphology: an annular lesion of individual papules, a dermal nodule, and a linear arrangement of 3 papules. Two of his lesions showed a palisading granuloma histology pattern of granuloma annulare; however, the linear papules on his posterior neck lesion demonstrated noncaseating granulomas consistent with either the epithelioid nodule histology pattern of granuloma annulare or sarcoidal granuloma compatible with sarcoidosis. A comprehensive evaluation excluded the diagnosis of systemic sarcoidosis. Using the PubMed database, an extensive literature search was performed on granuloma annulare, epithelioid nodule, sarcoidal granuloma, and sarcoidosis. The histology patterns of granuloma annulare-emphasizing the history and differentiating features of the epithelioid nodule pattern from cutaneous sarcoidosis-were reviewed. The epithelioid nodule (sarcoidal granuloma) histology pattern of granuloma annulare is uncommon and may mimic the histology changes observed in sarcoidosis skin lesions; the absence of asteroid or other giant cell inclusions and an increase in mucin deposition between the collagen bundles favor the diagnosis of granuloma annulare. In addition, the epithelioid nodule pattern of granuloma annulare can rarely also show other histologic patterns of granuloma annulare in the same biopsy specimen or concurrently present with other clinical lesions of granuloma annulare that demonstrate a palisading granuloma, or possibly an infiltrative, histology pattern. However, the presence of an isolated skin lesion demonstrating sarcoidal granulomas--even when concurrently appearing with other lesions of granuloma annulare showing either an infiltrative or a palisading granuloma histologic pattern--may prompt the clinician to evaluate and exclude the possibility of systemic sarcoidosis. PMID- 25140663 TI - Solitary Fibrous Tumor With Myxoid Stromal Change. AB - We report the case of a 46-year-old Korean woman who presented with a 5-month history of a hyperkeratotic plaque on the left palm. On examination, the plaque showed an annular pattern with an umbilicated central nodule and a peripheral palisading induration, which had a verrucous surface. After surgical resection, histopathologic analysis revealed that the tumor was composed of haphazardly arranged spindle cells and displayed a predominantly myxoid appearance in the stroma. The tumor cells were positive for CD34 and bcl-2, but negative for smooth muscle actin and S-100. The clinical manifestation and histopathologic findings were most consistent with a diagnosis of solitary fibrous tumor with myxoid stromal change. There was no evidence of recurrence or metastasis during the 8 month follow-up period. This case highlights the importance of an accurate diagnosis of solitary fibrous tumors, which may have extensive myxoid stromal change, hence mimicking other myxoid-type spindle cell tumors. PMID- 25140664 TI - Congenital melanocytic nevus: two clinicopathological forms. AB - Congenital melanocytic nevus (CMN) is a hamartomatous disease for which many attempts at classification have been proposed. This disease is relevant not only because of its functional and esthetic implications but also because it is a well documented precursor to malignant melanoma. We performed a clinical and pathological prospective study of 200 cases of CMN and were able to identify 2 different forms of CMN, each one with biological, clinical, and histopathological features and criteria that are consistent and repeatable. We propose to name them types I and II. Type I CMN is the most common, usually, if not always, a single lesion, it consists of a plaque that involves only 1 anatomic region and does not go beyond it; type I CNM grows in proportion to the growth of the child, melanoma rarely develops from it, and when it does it usually arises at the dermoepidermal junction. Its histopathology shows cords, strands, nests, and single units of melanocytes spreading between collagen bundles only in the dermis and frequently the epidermis too, but without trespassing to the hypodermis, that is, it is superficial. Type II CMN is always made up of many lesions, one of them being very large and surrounded by many lesions; histopathologically, it involves not only the skin but also deeper structures, sometimes bone and central nervous system; therefore, it is deep; when melanoma develops, it does in the dermal component and usually from the largest plaque. This type of CMN is the one that develops neurocutaneous melanocytosis. This system is not only easy and logical but it also has biologic advantages and the clinical-pathological correlation and criteria are repeatable by clinicians and pathologists. PMID- 25140666 TI - Cutaneous Pleomorphic Rhabdomyosarcoma Occurring on Sun-Damaged Skin: A Case Report. AB - Rhabdomyosarcoma (RMS) is a malignant soft tissue tumor with skeletal muscle differentiation that can rarely present as a primary cutaneous tumor. There are 3 main subtypes of RMS: embryonal, alveolar, and pleomorphic. Primary cutaneous pleomorphic RMS is extremely rare, there being only 9 reported cases in the literature, 2 of which are radiation induced. We present a case of primary pleomorphic RMS occurring on the sun-damaged skin of the face of an 89-year-old woman. The tumor was diagnosed by histology, immunohistochemistry, and electron microscopy. The patient was treated by surgery and adjuvant radiotherapy. The tumor recurred rapidly after surgical excision. She died 2 months after the diagnosis from complications of treatment, local symptoms of tumor, and concurrent illnesses. Primary cutaneous pleomorphic RMS is a rare tumor of adults and pursues an aggressive clinical course. PMID- 25140665 TI - Diffuse Reactive Angioendotheliomatosis Secondary to the Administration of Trabectedin and Pegfilgrastim. AB - Diffuse dermal angiomatosis is a rare benign condition considered a variant of reactive angioendotheliomatosis, usually related to vascular disease such as arteriovenous fistula or severe peripheral vascular disease. The most frequent clinical manifestations range from a solitary erythematous patch to an indurated plaque that may ulcerate. A clinical case of a 60-year-old woman who developed generalized livedoid lesions 2 days after the administration of intravenous trabectedin and subcutaneous pegfilgrastim for a recidivant myxoid liposarcoma has been reported. A biopsy of the skin lesions showed a pronounced proliferation of vessels in the upper dermis that was diagnosed as diffuse dermal angiomatosis. PMID- 25140667 TI - Langerhans Cell Hyperplasia From Molluscum Contagiosum. AB - Langerhans cell histiocytosis (LCH) carries a prognosis, which ranges from benign to potentially fatal. There is currently little framework to decipher metrics, which predict the benign versus aggressive nature of LCH. We wanted to determine whether molluscum contagiosum virus (MCV) DNA could be isolated from a cutaneous lesion, demonstrating Langerhans cell hyperplasia resembling LCH in a patient with both. Polymerase chain reaction on biopsy-proven MCV and the hyperplastic lesion has been performed. Two specific regions within the MCV genome were detected from both biopsies. The authors report our findings and suggest that some MCV can produce histological lesions resembling LCH, similar to the literature on scabies mimicking LCH. Efforts to find a reactive "driver" in LCH may significantly inform the clinical scenario. PMID- 25140668 TI - Rapid assessment of the coenzyme Q10 redox state using ultrahigh performance liquid chromatography tandem mass spectrometry. AB - An improved method for accurate and rapid assessment of the coenzyme Q10 (CoQ10) redox state using ultrahigh performance liquid chromatography tandem mass spectrometry was described, with particular attention given to the instability of the reduced form of CoQ10 during sample preparation, chromatographic separation and mass spectrometric detection. As highly lipophilic compounds in complex biological matrices, both reduced and oxidized forms of CoQ10 were extracted simultaneously from the tissue samples by methanol which is superior to ethanol and isopropanol. After centrifugation, the supernatants were immediately separated on a C18 column with isocratic elution using methanol containing 2 mM ammonium acetate as a non-aqueous mobile phase, and detected by positive electrospray ionization tandem mass spectrometry in multiple reaction monitoring (MRM) mode. Ammonium acetate as an additive in methanol provided enhanced mass spectrometric responses for both forms of CoQ10, primarily due to stable formation of adduct ions [M + NH4](+), which served as precursor ions in positive ionization MRM transitions. The assay showed a linear range of 8.6-8585 ng mL(-1) for CoQ10H2 and 8.6-4292 ng mL(-1) for CoQ10. The limits of detection (LODs) were 7.0 and 1.0 ng mL(-1) and limits of quantification (LOQs) were 15.0 and 5.0 ng mL(-1) for CoQ10H2 and CoQ10, respectively. This rapid extractive and analytical method could avoid artificial auto-oxidation of the reduced form of CoQ10, enabling the native redox state assessment. This reliable method was also successfully applied for the measurement of the CoQ10 redox state in liver tissues of mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin, revealing the down-regulated mitochondrial electron transport chain. PMID- 25140669 TI - Anterior tooth alignment: A comparison of orthodontic retention regimens 5 years posttreatment. AB - OBJECTIVE: To assess orthodontic treatment outcome at debonding and at 3 and 5 years after orthodontic treatment and to investigate the influence of different retention protocols on anterior tooth alignment. MATERIALS AND METHODS: Using the Peer Assessment Rating (PAR) Index, 169 patients (74 boys, 95 girls) were analyzed at four stages: pretreatment (T0), posttreatment (T1), 3 years posttreatment (T3), and 5 years posttreatment (T5). The PAR anterior component scores (ACSs) were compared between groups with different retention protocols. In the maxilla, protocols were removable retainer until T3 (MAX1), removable and fixed retainer until T3 (MAX2), and removable retainer until T3 and fixed retainer until T5 (MAX3). In the mandible, protocols were no retainer (MAND1), fixed 3-3 retainer until T3 (MAND2), and fixed 3-3 retainer until T5 (MAND3). RESULTS: Mean weighted improvement in PAR score was 88.3% at T1, 86.4% at T3, and 82.1% at T5. The ACS for the maxilla showed no significant differences between the retention protocols at any time point. In the mandible, the group without retention showed a gradual but not significant deterioration in ACS throughout the posttreatment period. At T5 there was a significant difference in ACS between the group that had the retainer removed at T3 and the group that kept the retainer. CONCLUSION: The 5-year treatment outcome, as measured by the PAR Index, was good. Stability of the maxillary anterior alignment 5 years posttreatment did not appear to be influenced by choice of retention protocol. Mandibular anterior alignment was significantly better for the group using a fixed retainer compared with the group where the retainer was removed 3 years posttreatment. PMID- 25140670 TI - Immunohistochemical expression of CD44 standard and E-cadherin in atypical leiomyoma and leiomyosarcoma of the uterus. AB - A family of cell adhesion molecules have been associated with tumorigenesis and tumour cell invasion. Cadherins and CD44 isoforms are transmembrane glycoproteins. Uterine smooth muscle tumours range from leiomyomas to leiomyosarcomas. However, separating malignant from benign can be difficult in a subset of smooth muscle tumours. Cell adhesion molecules expression may have diagnostic utility in the distinction of leiomyosarcoma from atypical leiomyoma. The aim of this study was to evaluate the diagnostic tool role of CD44 standard and E-cadherin in atypical leiomyoma and leiomyosarcoma. Paraffin blocks of 35 atypical leiomyoma and 22 leiomyosarcoma were analysed immunohistochemically for the expression CD44 standard and E-cadherin protein. Expression of CD44 standard was positive in all cases, while E-cadherin was negative. In this study, CD44 and E-cadherin were not useful for diagnostic tool to differentiate atypical leiomyoma from leiomyosarcoma. PMID- 25140671 TI - Base-promoted dehydrogenative coupling of benzene derivatives with amides or ethers. AB - Benzene derivatives are introduced into the dehydrogenative coupling via homolytic aromatic substitution (HAS) as arenes that couple with amides/ethers. NaOt-Bu is used as a critical promoter of HAS in combination with t-BuOOt-Bu as an oxidant. PMID- 25140672 TI - Risk factors of repeated infectious disease incidence among substance-dependent girls and boys court-referred to treatment. AB - BACKGROUND: A small portion of Americans account for a disproportionate amount of the incidences of sexually transmitted infection observed over a short period of time. Studies with adults have begun to characterize this population, yet there is very little data on adolescent sexually transmitted infection repeaters (STIR). This study explores characteristics associated with STIR among 102 girls and 93 boys (aged 14-18) court-referred for residential treatment. METHODS: Background characteristics, substance use disorders, risky and interpersonal behaviors, and history of sexually transmitted infections were collected at intake using valid and reliable instruments. A negative binomial logistic regression was performed to determine the background, risky behaviors, and social patterns associated with adolescent STIR. RESULTS: Approximately two out of three adolescents (62%) did not use contraception the last time they had sex, and 15% had at least one sexually transmitted infection recorded in their medical chart. Sexually transmitted infection repeaters entered treatment with higher rates of cocaine abuse (13%) than youth without multiple infections (3%, p < 0.05). History of sexual abuse, having sex with a person who said no, higher exhibitionism, and social estrangement increased the odds of adolescent STIR. Main effects of exhibitionism and social estrangement on increased odds of STIR were more pronounced for sexually abused adolescents. CONCLUSIONS: The findings suggest a need for incorporating HIV education during residential treatment to improve health outcomes and intervention strategies that further connectedness for youth and victims of sexual abuse. PMID- 25140673 TI - Associations between eating occasion characteristics and age, gender, presence of children and BMI among U.S. adults. AB - OBJECTIVE: To describe how frequency and characteristics of traditional meal and non-meal occasions vary by age, gender, presence of children, and body mass index (BMI). DESIGN: A cross-sectional survey was administered to a national demographically balanced sample of adults via an online market research panel. SETTING: Online survey. SUBJECTS: Survey respondents were in the 18- to 80-year old age range and had consumed any food or beverage at home or away from home the previous day. The sample included 2702 adults reporting on 6689 eating/drinking occasions. Most (80.3%) had no children at home; 43.5% were male and about two thirds were overweight/obese. MEASURES OF OUTCOME: Eating occasion characteristics and goals by age, gender, presence of children, and BMI. RESULTS: Older respondents were more likely to report planning traditional meal occasions and report on a breakfast occasion than younger respondents. Two prominent reasons that triggered consumption occasions were habit and hunger/thirst with one dominant benefit of satisfying hunger or thirst. Habit and nutrition played a larger role as a goal for eating occasions for older compared to younger respondents. When children were present in the household, respondents had a goal of connecting with "family, friends, or colleagues" at dinner compared to those without children. Few gender differences were noted; however, women more often reported goals of satisfying hunger/thirst and taste at lunch than men. BMI levels were related to a range of triggers, goals, and behaviors but not as prominently as the relationships observed with age. Those with BMI >= 30 were less health conscious regarding dinner and breakfast consumption compared to those with a lower BMI. CONCLUSIONS: Among demographic variables, age differences were noted in relation to eating occasion characteristics more often than other demographic characteristics or BMI. Understanding these differences can be beneficial in tailoring promotion of healthful intake at specific eating occasions for particular subgroups. PMID- 25140677 TI - Presenting the case for the medical humanities. PMID- 25140676 TI - Curing and caring competences in the skills training of physiotherapy students. AB - This article explores the significance of curing and caring competences in physiotherapy education, as well as how curing and caring competences intersect within the professional training of physiotherapy students. The empirical data include participant observations and interviews with students attending skills training in the first year of a bachelor's degree program in Norway. Curing and caring are conceptualized as gender-coded competences. That is, curing and caring are viewed as historical and cultural constructions of masculinities and femininities within the physiotherapy profession, as well as performative actions. The findings illuminate the complexity of curing and caring competences in the skills training of physiotherapy students. Curing and caring are both binary and intertwined competences; however, whereas binary competences are mostly concerned with contextual frames, intertwined competences are mostly concerned with performative aspects. The findings also point to how female and male students attend to curing and caring competences in similar ways; thus, the possibilities of transcending traditional gender norms turn out to be significant in this context. The findings suggest that, although curing somehow remains hegemonic to caring, the future generation of physiotherapists seemingly will be able to use their skills for both caring and curing. PMID- 25140679 TI - A night at the museum--helping residents "see" their patients. PMID- 25140678 TI - Fostering student engagement in medical humanities courses. PMID- 25140675 TI - Transcriptomic analysis of tail regeneration in the lizard Anolis carolinensis reveals activation of conserved vertebrate developmental and repair mechanisms. AB - Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first transcriptomic analysis of tail regeneration in a lizard, the green anole Anolis carolinensis, which revealed 326 differentially expressed genes activating multiple developmental and repair mechanisms. Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes significantly enriched in the regenerating tail. However, high levels of progenitor/stem cell markers were not observed in any region of the regenerating tail. Furthermore, we observed multiple tissue-type specific clusters of proliferating cells along the regenerating tail, not localized to the tail tip. These findings predict a different mechanism of regeneration in the lizard than the blastema model described in the salamander and the zebrafish, which are anamniote vertebrates. Thus, lizard tail regrowth involves the activation of conserved developmental and wound response pathways, which are potential targets for regenerative medical therapies. PMID- 25140680 TI - Do future bench researchers need humanities courses in medical school? PMID- 25140681 TI - Applied medical humanities: addressing vexing deficits, promoting enduring skills. PMID- 25140682 TI - FlexMed: a nontraditional admissions program at Icahn School of Medicine at Mount Sinai. PMID- 25140683 TI - Creating a space for the arts and humanities at the University of Colorado Anschutz Medical Campus. PMID- 25140684 TI - The ethical force of stories: narrative ethics and beyond. PMID- 25140685 TI - Use of art making in treating older patients with dementia. PMID- 25140686 TI - Expanding humanities training beyond medical school. PMID- 25140687 TI - A complete medical education includes the arts and humanities. PMID- 25140688 TI - Medical ethics and the media: the value of a story. PMID- 25140689 TI - Music and medicine: harnessing discipline and creativity. PMID- 25140690 TI - Tangles: an illness narrative in graphic form. PMID- 25140691 TI - "The best of doctors go to hell": how an ancient talmudic aphorism can inform the study and practice of medicine. PMID- 25140692 TI - Intranasal delivery of influenza rNP adjuvanted with c-di-AMP induces strong humoral and cellular immune responses and provides protection against virus challenge. AB - There is a critical need for new influenza vaccines able to protect against constantly emerging divergent virus strains. This will be sustained by the induction of vigorous cellular responses and humoral immunity capable of acting at the portal of entry of this pathogen. In this study we evaluate the protective efficacy of intranasal vaccination with recombinant influenza nucleoprotein (rNP) co-administrated with bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di AMP) as adjuvant. Immunization of BALB/c mice with two doses of the formulation stimulates high titers of NP-specific IgG in serum and secretory IgA at mucosal sites. This formulation also promotes a strong Th1 response characterized by high secretion of INF-gamma and IL-2. The immune response elicited promotes efficient protection against virus challenge. These results suggest that c-di-AMP is a potent mucosal adjuvant which may significantly contribute towards the development of innovative mucosal vaccines against influenza. PMID- 25140694 TI - Molecular epidemiology and antimicrobial susceptibility profiles of methicillin resistant Staphylococcus aureus blood culture isolates: results of the Quebec Provincial Surveillance Programme. AB - The objectives of this study were to characterize methicillin-resistant Staphylococcus aureus (MRSA) blood culture isolates and to determine their relative importance in both nosocomial and community-acquired infections. A total of 535 MRSA blood culture isolates were analysed. In vitro susceptibility to 14 agents was determined. The genes nuc, mecA and coding for PVL toxin were identified by PCR. All isolates were characterized by PFGE or spa typing to assess their genomic relationships. Most MRSA isolates were retrieved from nosocomial bloodstream infections (474, 89%) and were of the CMRSA2 genotype. Healthcare-associated (HA)-MRSA bloodstream infections were associated with older age (70-89 years, P = 0.002) and most often secondary to central line infections (P = 0.005). Among MRSA strains associated with community-acquired (CA)-MRSA, 28.8% were isolated in intravenous drug users. CA-MRSA genotypes were more frequently found in young adults (20-39 years, P < 0.0001) with skin/soft tissue as the primary sources of infection (P = 0.006). CMRSA10 genotype was the predominant CA-MRSA strain. All MRSA isolates were susceptible to doxycycline, tigecycline, trimethoprim/sulfamethoxazole and vancomycin. Both the presence of the genes coding for PVL toxin (89.8%) and susceptibility to clindamycin (86.5%) were predictive of CA-MRSA genotypes. Whereas in the USA, HA-MRSA have been replaced by USA300 (CMRSA10) clone as the predominant MRSA strain type in positive blood cultures from hospitalized patients, this phenomenon has not been observed in the province of Quebec. PMID- 25140695 TI - Synergistic effect of viral load and alcohol consumption on the risk of persistent high-risk human papillomavirus infection. AB - PURPOSE: This prospective study aimed to examine the combined effect of viral load and alcohol consumption on the risk of persistent high-risk (HR) human papillomavirus (HPV) infection. METHODS: Among women undergoing health screening between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR HPV infection and cytological findings of low-grade squamous intraepithelial or lower-grade lesions were followed up for 1 and 2 years, respectively. Multivariate logistic regression analysis was performed, and the relative excess risk due to interaction (RERI) and synergy index (S) were calculated. RESULTS: Among drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.05-8.18) and 2-year persistence (OR 8.08, CI 2.36-27.6) were significantly higher for high HPV loads than for low HPV loads; this association was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89-9.05) and 2 year persistence (OR 6.61, CI 2.09-20.9) were significantly higher in subjects with a high HPV load who were also drinkers than in those who were non-drinkers. A high HPV load together with a longer drinking duration or higher alcohol consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40-6.75 or OR 2.05, CI 0.87-4.83) and 2-year persistence (OR 6.40, CI 1.72-23.8 or OR 4.14, CI 1.18-14.6). The synergistic effect of alcohol consumption and HR-HPV load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38) than on the risk of 1-year persistence (RERI = 1.21, S = 1.63). CONCLUSIONS: The synergistic effect of HR-HPV load and alcohol consumption was associated with the risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection. Limiting alcohol consumption might be an important measure to prevent the development of cervical cancer in women with a high HR-HPV load. PMID- 25140698 TI - Why the product labeling for low-dose vaginal estrogen should be changed. PMID- 25140697 TI - Extent of mangrove nursery habitats determines the geographic distribution of a coral reef fish in a South-Pacific archipelago. AB - Understanding the drivers of species' geographic distribution has fundamental implications for the management of biodiversity. For coral reef fishes, mangroves have long been recognized as important nursery habitats sustaining biodiversity in the Western Atlantic but there is still debate about their role in the Indo Pacific. Here, we combined LA-ICP-MS otolith microchemistry, underwater visual censuses (UVC) and mangrove cartography to estimate the importance of mangroves for the Indo-Pacific coral reef fish Lutjanus fulviflamma in the archipelago of New Caledonia. Otolith elemental compositions allowed high discrimination of mangroves and reefs with 83.8% and 98.7% correct classification, respectively. Reefs were characterized by higher concentrations of Rb and Sr and mangroves by higher concentrations of Ba, Cr, Mn and Sn. All adult L. fulviflamma collected on reefs presented a mangrove signature during their juvenile stage with 85% inhabiting mangrove for their entire juvenile life (about 1 year). The analysis of 2942 UVC revealed that the species was absent from isolated islands of the New Caledonian archipelago where mangroves were absent. Furthermore, strong positive correlations existed between the abundance of L. fulviflamma and the area of mangrove (r = 0.84 for occurrence, 0.93 for density and 0.89 for biomass). These results indicate that mangrove forest is an obligatory juvenile habitat for L. fulviflamma in New Caledonia and emphasize the potential importance of mangroves for Indo-Pacific coral reef fishes. PMID- 25140696 TI - Similar prevalence of low-abundance drug-resistant variants in treatment-naive patients with genotype 1a and 1b hepatitis C virus infections as determined by ultradeep pyrosequencing. AB - BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) variants that confer resistance to direct-acting-antiviral agents (DAA) have been detected by standard sequencing technology in genotype (G) 1 viruses from DAA-naive patients. It has recently been shown that virological response rates are higher and breakthrough rates are lower in G1b infected patients than in G1a infected patients treated with certain classes of HCV DAAs. It is not known whether this corresponds to a difference in the composition of G1a and G1b HCV quasispecies in regards to the proportion of naturally occurring DAA-resistant variants before treatment. METHODS: We used ultradeep pyrosequencing to determine the prevalence of low abundance (<25% of the sequence reads) DAA-resistant variants in 191 NS3 and 116 NS5B isolates from 208 DAA-naive G1-infected patients. RESULTS: A total of 3.5 million high-quality reads of >= 200 nucleotides were generated. The median coverage depth was 4150x and 4470x per NS3 and NS5B amplicon, respectively. Both G1a and G1b populations showed Shannon entropy distributions, with no difference between G1a and G1b in NS3 or NS5B region at the nucleotide level. A higher number of substitutions that confer resistance to protease inhibitors were observed in G1a isolates (mainly at amino acid 80 of the NS3 region). The prevalence of amino acid substitutions that confer resistance to NS5B non nucleoside inhibitors was similar in G1a and G1b isolates. The NS5B S282T variant, which confers resistance to the polymerase inhibitors mericitabine and sofosbuvir, was not detected in any sample. CONCLUSION: The quasispecies genetic diversity and prevalence of DAA-resistant variants was similar in G1a and G1b isolates and in both NS3 and NS5B regions, suggesting that this is not a determinant for the higher level of DAA resistance observed across G1a HCV infected patients upon treatment. PMID- 25140701 TI - Identification and characterization of phenol hydroxylase from phenol-degrading Candida tropicalis strain JH8. AB - The gene phhY encoding phenol hydroxylase from Candida tropicalis JH8 was cloned, sequenced, and expressed in Escherichia coli. The gene phhY contained an open reading frame of 2130 bp encoding a polypeptide of 709 amino acid residues. From its sequence analysis, it is a member of a family of flavin-containing aromatic hydroxylases and shares 41% amino acid identity with phenol hydroxylase from Trichosporon cutaneum. The recombinant phenol hydroxylase exists as a homotetramer structure with a native molecular mass of 320 kDa. Recombinant phenol hydroxylase was insensitive to pH treatment; its optimum pH was at 7.6. The optimum temperature for the enzyme was 30 degrees C, and its activity was rapidly lost at temperatures above 60 degrees C. Under the optimal conditions with phenol as substrate, the K(m) and V(max) of recombinant phenol hydroxylase were 0.21 mmol.L(-1) and 0.077 MUmol.L(-1).min(-1), respectively. This is the first paper presenting the cloning and expression in E. coli of the phenol hydroxylase gene from C. tropicalis and the characterization of the recombinant phenol hydroxylase. PMID- 25140702 TI - Trends in Patterns of Posterior Uveitis and Panuveitis in a Tertiary Institution in Singapore. AB - PURPOSE: The study aims to analyze the trends of posterior uveitis and panuveitis patients seen by a tertiary eye center in Singapore between 2004 and 2012. METHODS: We conducted a retrospective analysis of 363 consecutive new cases of posterior uveitis and panuveitis. The cases were segregated into idiopathic, infectious, or noninfectious. RESULTS: We found statistically significant differences between etiologies and ethnicity (p = 0.014). We noticed a statistically significant downward trend (Spearman's rho (rho) = -0.812, p = 0.008) for dengue uveitis, and an upward trend for the idiopathic category (Spearman's rho (rho) = 0.753, p = 0.019). CONCLUSIONS: We observed differences between etiologies and ethnicity, pointing toward potential susceptibility variations. There was an upward trend of idiopathic causes, possibly due to better control of systemic and infectious etiologies. The dengue uveitis incidence correlates well with our national statistics. The downward trend of dengue uveitis could be due to the introduction of Singapore's dengue surveillance in 2005, emphasizing the importance of controlling the disease. PMID- 25140699 TI - Morning surge of ventricular arrhythmias in a new arrhythmogenic canine model of chronic heart failure is associated with attenuation of time-of-day dependence of heart rate and autonomic adaptation, and reduced cardiac chaos. AB - Patients with chronic heart failure (CHF) exhibit a morning surge in ventricular arrhythmias, but the underlying cause remains unknown. The aim of this study was to determine if heart rate dynamics, autonomic input (assessed by heart rate variability (HRV)) and nonlinear dynamics as well as their abnormal time-of-day dependent oscillations in a newly developed arrhythmogenic canine heart failure model are associated with a morning surge in ventricular arrhythmias. CHF was induced in dogs by aortic insufficiency & aortic constriction, and assessed by echocardiography. Holter monitoring was performed to study time-of-day-dependent variation in ventricular arrhythmias (PVCs, VT), traditional HRV measures, and nonlinear dynamics (including detrended fluctuations analysis alpha1 and alpha2 (DFAalpha1 & DFAalpha2), correlation dimension (CD), and Shannon entropy (SE)) at baseline, as well as 240 days (240 d) and 720 days (720 d) following CHF induction. LV fractional shortening was decreased at both 240 d and 720 d. Both PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8 fold increase at 6 AM-noon vs midnight-6 AM) during CHF. The morning rise in HR at baseline was significantly attenuated by 52% with development of CHF (at both 240 d & 720 d). Morning rise in the ratio of low frequency to high frequency (LF/HF) HRV at baseline was markedly attenuated with CHF. DFAalpha1, DFAalpha2, CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day dependent variations in LF/HF, CD, DFA alpha1 and SE, observed at baseline, were lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and complexity of heart rate, as well as aberrant time-of-day-dependent variations in many of these parameters were associated with a morning surge of ventricular arrhythmias. PMID- 25140703 TI - Triaxial transarterial embolization for lower gastrointestinal bleeding: a retrospective case series. AB - OBJECTIVE: Superselective transcatheter arterial embolization (TAE) is important for lower gastrointestinal (GI) bleeding. A new 1.9-Fr. no-taper microcatheter has recently become available and can be inserted into a 2.7-Fr. microcatheter. We assessed the applicability of this new triple co-axial (triaxial) system to TAE for lower GI bleeding. MATERIAL AND METHODS: Five patients with lower GI bleeding underwent TAE with the triaxial system. The approach was via the femoral artery with a 4-Fr. sheath in all cases. The 4-Fr. catheter and triaxial system were inserted into the artery in which extravasation had occurred. Coil embolization was performed with 0.010-inch coils. We evaluated technical success rate, clinical success rate and complications. RESULTS: All five cases of bleeding occurred at the ascending colon, and were caused by diverticulosis in four cases, and an injury to the artery during polypectomy in one case. The 1.9 Fr. no-taper microcatheter could be inserted into the site of extravasation, the vasa recta, in all procedures and TAE was performed successfully. The disappearance of extravasation was confirmed in all cases following TAE. No patients exhibited any signs of recurrent bleeding or complication. CONCLUSION: The triaxial system appears to be effective and useful in superselective TAE for lower GI bleeding. PMID- 25140704 TI - CRISPR/Cas9-mediated gene knock-down in post-mitotic neurons. AB - The prokaryotic adaptive immune system CRISPR/Cas9 has recently been adapted for genome editing in eukaryotic cells. This technique allows for sequence-specific induction of double-strand breaks in genomic DNA of individual cells, effectively resulting in knock-out of targeted genes. It thus promises to be an ideal candidate for application in neuroscience where constitutive genetic modifications are frequently either lethal or ineffective due to adaptive changes of the brain. Here we use CRISPR/Cas9 to knock-out Grin1, the gene encoding the obligatory NMDA receptor subunit protein GluN1, in a sparse population of mouse pyramidal neurons. Within this genetically mosaic tissue, manipulated cells lack synaptic current mediated by NMDA-type glutamate receptors consistent with complete knock-out of the targeted gene. Our results show the first proof-of principle demonstration of CRISPR/Cas9-mediated knock-down in neurons in vivo, where it can be a useful tool to study the function of specific proteins in neuronal circuits. PMID- 25140706 TI - Belatacept-based immunosuppression in a chagasic adult recipient of en bloc pediatric kidneys. PMID- 25140705 TI - The neural bases of directed and spontaneous mental state attributions to group agents. AB - In daily life, perceivers often need to predict and interpret the behavior of group agents, such as corporations and governments. Although research has investigated how perceivers reason about individual members of particular groups, less is known about how perceivers reason about group agents themselves. The present studies investigate how perceivers understand group agents by investigating the extent to which understanding the 'mind' of the group as a whole shares important properties and processes with understanding the minds of individuals. Experiment 1 demonstrates that perceivers are sometimes willing to attribute a mental state to a group as a whole even when they are not willing to attribute that mental state to any of the individual members of the group, suggesting that perceivers can reason about the beliefs and desires of group agents over and above those of their individual members. Experiment 2 demonstrates that the degree of activation in brain regions associated with attributing mental states to individuals--i.e., brain regions associated with mentalizing or theory-of-mind, including the medial prefrontal cortex (MPFC), temporo-parietal junction (TPJ), and precuneus--does not distinguish individual from group targets, either when reading statements about those targets' mental states (directed) or when attributing mental states implicitly in order to predict their behavior (spontaneous). Together, these results help to illuminate the processes that support understanding group agents themselves. PMID- 25140707 TI - Benevolent characteristics promote cooperative behaviour among humans. AB - Cooperation is fundamental to the evolution of human society. We regularly observe cooperative behaviour in everyday life and in controlled experiments with anonymous people, even though standard economic models predict that they should deviate from the collective interest and act so as to maximise their own individual payoff. However, there is typically heterogeneity across subjects: some may cooperate, while others may not. Since individual factors promoting cooperation could be used by institutions to indirectly prime cooperation, this heterogeneity raises the important question of who these cooperators are. We have conducted a series of experiments to study whether benevolence, defined as a unilateral act of paying a cost to increase the welfare of someone else beyond one's own, is related to cooperation in a subsequent one-shot anonymous Prisoner's dilemma. Contrary to the predictions of the widely used inequity aversion models, we find that benevolence does exist and a large majority of people behave this way. We also find benevolence to be correlated with cooperative behaviour. Finally, we show a causal link between benevolence and cooperation: priming people to think positively about benevolent behaviour makes them significantly more cooperative than priming them to think malevolently. Thus benevolent people exist and cooperate more. PMID- 25140710 TI - Relationship between periodontal disease and obesity: the role of life-course events. AB - Periodontal disease is ranked among the 10 most prevalent chronic diseases worldwide, and is considered a major public health problem. Its etiology has been associated with local and general conditions that could interfere in the host immune response. Obesity, like periodontal disease, has emerged as a prevalent chronic disease in high-, low- and medium-income countries, recognized as risk factor for cardiovascular disease and cancer. A relationship between periodontal health and obesity may exist, but the mechanism that would explain this association remains unclear. Life-course epidemiology could be a useful instrument to investigate a casual association between early exposures and later outcomes, being appropriate for understanding the establishment of chronic conditions. This approach comprehends different theories, considering the time, the duration and the intensity of early exposition, and its impact on the development of chronic diseases in later life. Thus, the aim of this study is to hypothesize the different life-course epidemiology theories to explain the possible association between periodontal health and nutritional status in adulthood. PMID- 25140709 TI - Prevalence and trends in obesity among China's children and adolescents, 1985 2010. AB - OBJECTIVES: We examined the prevalence of and trends in obesity among children and adolescents in China (1985-2010). METHODS: We used data from the 1985, 1991, 1995, 2000, 2005, and 2010 Chinese National Surveys on Students' Constitution and Health (CNSSCH). The CNSSCH is a national survey of physical fitness and health status in Chinese students that uses multistage stratified sampling of 31 provinces and municipalities. A subject was considered obese or overweight if weight-for-height exceeded the 20% or 10% of standard weight-for-height. The standard weight-for-height was the 80th percentile for sex- and age-specific growth charts. RESULTS: The age-adjusted prevalence of obesity and of overweight and obesity combined was 8.1% (95% CI, 8.0-8.3%) and 19.2% (95% CI, 19.1-19.4%) among children and adolescents 7-18 years in age. Obesity was more likely to be present among children or adolescents who were male (RR, 1.93; 95% CI, 1.90 1.97), urban (RR, 1.99; 95% CI, 1.95-2.02), or 10-12 years (RR, 1.43; 95% CI, 1.40-1.46). Trend analyses of the 25-year period revealed a significant increasing trend in males (RR, 1.59; 95% CI, 1.58-1.60) and in females (RR, 1.49; 95% CI, 1.48-1.50). The rate of increase in obese or overweight prevalence was highest in boys from rural areas (9% annual increase). CONCLUSIONS: During 1985 2010, there was a significant and continuous increase in the prevalence of obesity in children and adolescents. Obesity is epidemic in China, but may be reduced with evidence-based interventions (e.g., school intervention programs). PMID- 25140711 TI - Effects of nonsurgical periodontal treatment on the alveolar bone density. AB - The aim of this study was to evaluate the effects of nonsurgical periodontal treatment on alveolar bone density (ABD) and bone height (BH) using direct digital radiography. Nineteen patients (mean age: 36 +/- 7.3 years) with generalized chronic periodontitis were examined at baseline, 90 (90 AT) and 180 (180 AT) days after nonsurgical periodontal therapy. Radiographs were taken from two sites with specific characteristics: 39 sites with probing pocket depth (PPD) <= 3 mm and clinical attachment level (CAL) <= 1 mm (shallow sites); and 62 sites with PPD >= 5 mm and CAL >= 3 mm (deep sites). The ABD was assessed considering the bone regions of interest at the alveolar bone crest (ROI I) and at the medullar bone (ROI II). The BH was assessed considering the distance from the alveolar bone crest to the cementoenamel junction. Mann-Whitney test was used for the overall demographic data, Wilcoxon test was used to compare the baseline, 90 AT and 180 AT data as well as to compare the groups and subgroups within the same evaluation period. The significance level was set at 5%. The deep sites showed a significant increase of ABD in ROI I at 90 AT (p<0.007) and at 180 AT (p<0.005). ABD decrease was seen in ROI II at 180 AT (p<0.04) while BH reduced only in shallow sites at 90 AT. In conclusion, an increase in ABD was observed in deep sites of patients with generalized chronic periodontitis. However, no significant change in alveolar BH was observed in these sites. PMID- 25140712 TI - Effects of titanium surfaces on the developmental profile of monocytes/macrophages. AB - Due to the critical role of monocytes/macrophages (Mphi) in bone healing, this study evaluated the effects of bio-anodized, acid-etched, and machined titanium surfaces (Ti) on Mphi behavior. Cells were separated from whole human blood from 10 patients, plated on Ti or polystyrene (control) surfaces, and cultured for 72 h. At 24, 48 and 72 h, cell viability, levels of IL1beta, IL10, TNFalpha, TGFbeta1 inflammatory mediators, and nitric oxide (NO) release were analyzed by mitochondrial colorimetric assay (MTT assay) and immunoenzymatic assays, respectively. Real-time PCR was used to verify the expression of TNFalpha and IL10 at 72 h. The data were subjected to a Kruskal-Wallis analysis. IL1beta, TNFalpha and TGFbeta1 release were not significantly different between the Ti surfaces (p>0.05). The presence of NO and IL10 was not detected in the samples. Cell viability did not differ between the samples cultivated on Ti and those cultivated on control surfaces, except at 24 h (p=0.0033). With respect to the mediators evaluated, the surface characteristics did not induce a typical Th1 or Th2 cytokine profile, although the cell morphology and topography were influenced by the Ti surface during the initial period. PMID- 25140713 TI - Biocompatibility of a calcium hydroxide-propolis experimental paste in rat subcutaneous tissue. AB - Intracanal medications are fundamental for disinfection of the root canal system and participate in periapical repair, so their biocompatibility is of utmost importance to avoid tissue damage. This study evaluated the biocompatibility of a experimental paste of calcium hydroxide and propolis in the subcutaneous tissue of rats. The study was conducted on 15 male Wistar rats. Two incisions were made on the dorsal region of each animal for introduction of 4 tubes: one tube was empty; one contained zinc oxide-eugenol cement, and the two other tubes were filled with experimental paste. After 7, 14 and 30 days, the animals were euthanized and the specimens were subjected to histotechnical preparation. The hematoxylin and eosin-stained histological sections were analyzed by light microscopy. Scores were established according to the inflammatory process and statistically compared by the Tukey test (alpha = 5%). The analysis of histological sections showed non-significant or mild inflammatory reaction in the connective tissue in contact with the empty tubes in all study periods while the contact of subcutaneous tissue with zinc oxide-eugenol elicited moderate or severe inflammation similarly without significant difference among the study periods. The connective tissue was moderately inflamed at 7 days when contacting the experimental paste, but the inflammatory process was non-significant or mild at 14 and 30 days. The experimental paste was biocompatible with the tissues after 14 days of subcutaneous implantation. PMID- 25140714 TI - Detection of organochlorine compounds formed during the contact of sodium hypochlorite with dentin and dental pulp. AB - This study used gas chromatography-mass spectrometry (GC-MS) to detect the products formed during the contact of sodium hypochlorite (NaOCl) with bovine pulp and dentin. For analysis of the products formed in the volatile phase, 11 mg of bovine pulp tissue were placed in contact with 0.5%, 2.5% and 5.25% NaOCl until complete tissue dissolution occurred. The solid phase microextraction (SPME) fiber was exposed inside the container through the cover membrane and immediately injected into the GC-MS system. 30 mg of the of dentin were kept in contact with NaOCl, and then the SPME fiber was exposed inside the container through the cover membrane for adsorption of the products and injected into the GC-MS system. The same protocol was used for the aqueous phase. For analysis of the volatile compounds, the final solution was extracted using pure ethyl ether. The suspended particulate phase of the mixture was aspirated, and ether was separated from the aqueous phase of the solution. The ether containing the products that resulted from the chemical interaction of dentin and pulp with the NaOCl was filtered and then injected into the GC-MS system for analysis of the aqueous phase. The aqueous and volatile phases of both dentin and pulp showed the formation of chloroform, hexachloroethane, dichloromethylbenzene and benzaldehyde. In conclusion, organochlorine compounds are generated during the contact of dentin and pulp with NaOCl at concentrations of 0.5%, 2.5% and 5.25%. PMID- 25140715 TI - Influence of sealer placement technique on the quality of root canal filling by lateral compaction or single cone. AB - The aim of this study was to evaluate the influence of the sealer placement technique on the quality of root canal filling using Lateral Compaction (LC) or Single Cone (SC). In order to do that, 60 mesial roots of mandibular first molars were prepared and divided into 2 groups (n=30), according to the filling technique: LC and SC. Each group was subdivided into 3 subgroups (n=10), according to the different sealer placement methods: A: Master gutta-percha (GP) cone; B: Lentulo spiral; C: File. The roots were sectioned at 2, 4 and 6 mm from the apex and photographed with the aid of a digital microscope. Then, areas of GP, endodontic sealer and voids were measured, and these data were subjected to statistical analysis. LC technique showed no statistically difference (p>0.05) in the percentage of GP area, sealer and voids between the subgroups at any of the three levels. After use of SC, higher percentages of sealer area were found at all levels (p<0.01) when the sealer was placed with a file. At 2 mm, higher percentage of void areas (p<0.05) was observed when the cone was used, lower percentage with K-file and the lowest percentage with Lentulo. At 4 mm, cone showed higher percentage of void areas (p<0.05). At 6 mm, there were no significant differences (p>0.05) between the three methods. Considering these results, using an instrument for sealer placement was important in the SC technique to reduce voids. Regarding LC, the sealer placement techniques provided similar results. PMID- 25140716 TI - Periapical status and prevalence of endodontic treatment in institutionalized elderly. AB - The aim of this study was to determine the prevalence and frequency of apical periodontitis and root fillings in 450 institutionalized Brazilian elderly. The teeth with apical periodontitis were assessed using the Periapical Index (PAI) score. A total of 942 teeth were evaluated in 98 subjects (57 females and 41 males) with mean age of 74 years. The observed frequency of total edentulous subjects was high (76%) in this population. A total of 126 teeth showed root fillings, of these only 46 (36.5%) were scored as having adequate quality. Apical periodontitis was found in 114 teeth (12.1%) in 42 (42.9%) subjects. 80 (70.2%) inadequate root-filled teeth showed apical periodontitis. There was a significant correlation between the presence of periapical pathology and inadequate root filled teeth. Inadequate root-filled teeth were associated with an increased prevalence of apical periodontitis in these subjects. This fact may result in increased endodontic retreatment needs for this population. PMID- 25140717 TI - Canal preparation and filling techniques do not influence the fracture resistance of extensively damaged teeth. AB - The purpose of this study was to assess the fracture resistance of extensively damaged teeth after two root canal preparation techniques (hand and rotary files) and after two filling techniques (active and passive compaction). Sixty-eight maxillary canines roots with an apical diameter equal to that of a #25 K-file were embedded in acrylic resin and the periodontal ligament was simulated by using a polyether impression material. The roots were randomly distributed into four groups (n=17): hand preparation and active compaction (HA), hand preparation and passive compaction (HP), rotary preparation and active compaction (RA), and rotary preparation and passive compaction (RP). All roots were restored with glass fiber post and metallic crown. The specimens were mechanically cycled (500,000 cycles, 45 degrees , 37 degrees C, 133 N, 2 Hz) and then subjected to a fracture resistanhe fracture resistance values ranged between 621.15 N (HP) and 785.71 N (HA). However, the Kruskal-Wallis test did not reveal differences in the fracture ce test. A single blinded examiner analyzed the external root surface and classified the failure pattern as favorable or unfavorable. Tresistance values among the four groups (p =0.247). Under the tested conditions, root canal preparation and filling techniques had no influence on the fracture resistance of extensively damaged teeth restored with fiber post and metallic crown. PMID- 25140718 TI - In vitro tensile strength of luting cements on metallic substrate. AB - The aim of this study was to determine the tensile strength of crowns cemented on metallic substrate with four different types of luting agents. Twenty human maxillary molars with similar diameters were selected and prepared to receive metallic core castings (Cu-Al). After cementation and preparation the cores were measured and the area of crown's portion was calculated. The teeth were divided into four groups based on the luting agent used to cement the crowns: zinc phosphate cement; glass ionomer cement; resin cement Rely X; and resin cement Panavia F. The teeth with the crowns cemented were subjected to thermocycling and later to the tensile strength test using universal testing machine with a load cell of 200 kgf and a crosshead speed of 0.5 mm/min. The load required to dislodge the crowns was recorded and converted to MPa/mm(2). Data were subjected to Kruskal-Wallis analysis with a significance level of 1%. Panavia F showed significantly higher retention in core casts (3.067 MPa/mm(2)), when compared with the other cements. Rely X showed a mean retention value of 1.877 MPa/mm(2) and the zinc phosphate cement with 1.155 MPa/mm(2). Glass ionomer cement (0.884 MPa/mm(2)) exhibited the lowest tensile strength value. Crowns cemented with Panavia F on cast metallic posts and cores presented higher tensile strength. The glass ionomer cement showed the lowest tensile strength among all the cements studied. PMID- 25140719 TI - Addition of silver nanoparticles to composite resin: effect on physical and bactericidal properties in vitro. AB - The objectives of this study were to evaluate physical properties and antibacterial activity of a light-activated composite modified with silver nanoparticles. Discs were produced with unmodified resin (control group - CG) and modified resin with silver nanoparticles at two concentrations, 0.3% wt (MR03) and 0.6% wt (MR06). Streptococcus mutans and Lactobacillus acidophilus biofilms were induced in vitro by incubation of discs in a 20% sucrose medium, followed by sonication and counting of viable cells after 1, 4 and 7 days (n=9). The arithmetic roughness of all three groups was evaluated by atomic force microscopy (n=9). Compression assay was conducted in all groups to measure the compressive strength at failure and elasticity modulus (n=5). Data were subjected to ANOVA and Tukey's tests (alpha=0.05%). At all three time points the number of viable cells was statistically lower for MR03 and MR06 compared with CG, for both specimens. MR03 and MR06 showed no significant differences. Microscopic analysis demonstrated no significant differences for roughness among the three groups (p>0.05). The MR03 was stronger to compression than CG, and MR06 was statistically lower than CG and MR03. It was concluded that the MR03 were less conducive to biofilm growth, without compromising the strength in compression and surface roughness. PMID- 25140720 TI - Assessment of tooth structure using an alternative electrical bioimpedance spectroscopy method. AB - In the past few years bioimpedance has been used in many applications in dentistry, such as estimating the length of root canals and the physical properties of enamel. Despite the significant number of studies using bioimpedance to investigate the dental structure, many of them use only the real component of bioimpedance, i.e., the resistance, disregarding the information provided by the imaginary one, i.e., the reactance. Moreover, in different studies that investigate both parts of bioimpedance, the data are obtained by using single frequency or multifrequency methods based on sinusoidal sweep. The aim of this study was to investigate the use of an alternative bioimpedance spectroscopy (BIS) method based on step response in the assessment of tooth structure. To test the feasibility of the studied method we performed in vitro experiments that considered the successive removal of enamel layers of 22 healthy teeth, the accomplishment of the BIS method, and the estimate of bioimpedance parameter that were associated with the changes in the tooth structure. To deal with the variability of bioimpedance parameters a dental health index (DHI) is proposed. The findings include the behavior of bioimpedance parameters of intact teeth, as well as those associated with the successive removal of the enamel layer, and indicate that DHI is sensitive enough to detect changes of the enamel layer. The results point to the feasibility of the studied BIS method in evaluating tooth structure and that it might be used to assess dental health. PMID- 25140721 TI - Characterization of dentifrices containing desensitizing agents, triclosan or whitening agents: EDX and SEM analysis. AB - Dentifrices with different compositions are available on the market, but there is limited information about their properties. The aim of this in vitro study was to evaluate the physicochemical characteristics of 12 dentifrices divided into three categories, as containing desensitizing agents, Triclosan or whitening agents. Desiccation loss/residue analysis: 5 g of dentifrice was weighed five times for each group. pH analysis: 5 g of dentifrice were diluted in three parts of distilled water and analyzed using a digital potentiometer. Scanning electron microscopy (SEM): analysis of ashes, shape and size of the particles. Energy dispersive x-ray spectroscopy (EDX): identification of the abrasive elements. Data were analyzed using ANOVA, Bonferroni post hoc test (alpha=0.05). Desiccation loss: 38.21% to 65.83%. Dentifrices containing Triclosan and desensitizing agents showed statistically significant differences among them (p<0.05). Whitening dentifrices showed statistically significant differences between Close-Up Whitening and Sensodyne Branqueador (44.72%, 65.83%, respectively). Most dentifrices presented neutral or basic pH. Different shape and size particles were observed in the SEM analysis. Abrasive elements were identified in the EDX. These results demonstrate that the evaluated dentifrices had different properties and their composition influences directly their characteristics, thus resulting in a more or less abrasive action on tooth surface. Knowing the characteristics of the dentifrices is important to indicate the ideal product for each case. PMID- 25140722 TI - Insoluble NaF in Duraphat(r) may prolong fluoride reactivity of varnish retained on dental surfaces. AB - There is no consensus about the clinical recommendation of the time that Duraphat(r) varnish should be maintained on enamel surfaces without suffering mechanical disturbance by the patient. Considering the importance of calcium fluoride (CaF2)-like reservoirs on the anticaries effect of professional fluoride application, an in vitro study was designed to test the reactivity of Duraphat(r) varnish with enamel forming these reservoirs as a function of time. Since most fluoride in Duraphat(r) varnish is insoluble to react and form products on enamel, the relative contribution of the varnish soluble and insoluble fluoride fractions to the reactivity was also evaluated. For this, whole-varnish, containing soluble and insoluble fluoride (total fluoride concentration of 23699 +/- 384 ug F/g), or centrifuged varnish, containing only soluble fluoride (fluoride concentration of 258 +/- 97 ug F/g), were applied in a standardized manner on enamel slabs (n=8/varnish group/time), which were immersed in continuously renewed artificial saliva for up to 36 h. CaF2-like reservoirs formed on enamel by varnish application were extracted using 1 M KOH and fluoride concentration was measured with ion specific electrode. The results were expressed as ug F/cm(2) of enamel area. Whole varnish formed significantly higher fluoride concentration on enamel than centrifuged varnish, reaching maximum concentration at 24 h (22.0 +/- 4.5 ug F/cm(2)). Centrifuged varnish reached maximum concentration at 6 h (3.20 +/- 0.81 ug F/cm(2)). In conclusion, a longer varnish retention time than the usually recommended could improve the anticaries effect of Duraphat(r) varnish, allowing that NaF particles, initially insoluble in the varnish matrix, prolong the reactivity with enamel. PMID- 25140723 TI - Antimicrobial activity and synergism of lactoferrin and lysozyme against cariogenic microorganisms. AB - The present study evaluated the antimicrobial in vitro effects of the salivary proteins lactoferrin and lysozyme on microorganisms involved in the carious process, obtaining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Streptococcus mutans (ATCC 25175) and Lactobacillus casei (ATCC 7469) were submitted to broth macrodilution of lysozyme at 80 mg/mL and lactoferrin at 200 mg/mL. The tubes were read in a spectrophotometer after they had been incubated at 37 degrees C for 18 h, in a carbon dioxide chamber, in order to read the MIC. A new subculture was carried on agar plates to obtain the MBC. The agar diffusion method was also tested, using BHI agar with 100 uL of the standardized microbial inocula. Filter-paper disks soaked in 10 uL of the solutions lactoferrin (200 ug/mL) and lysozyme (80 ug/mL) were placed on the agar surface. Inhibition halos were not observed on the plates, showing the absence of the antimicrobial effects of these proteins in this method. The bactericidal and bacteriostatic effects of lysozyme on L. casei were 50.3 mg/mL and 43.1 mg/mL respectively. The bactericidal and bacteriostatic effects on S. mutans were 68.5 mg/mL and 58.7 mg/mL. Lactoferrin did not induce any inhibitory effects on any microorganism, even in the concentration of 200 mg/mL. There was not a synergic antimicrobial effect of proteins, when they were tested together, even in the concentration of 42.8 mg/mL of lysozyme and 114 mg/mL of lactoferrin (the highest values evaluated). S. mutans and L. casei were only inhibited by lysozyme, not affected by lactoferrin and by the synergic use of both proteins. PMID- 25140724 TI - Anteroposterior and vertical changes in skeletal class II patients treated with modified Thurow appliance. AB - The aim of this study was to evaluate the post-treatment anteroposterior and vertical alterations in skeletal Class II malocclusion with different maxillary patterns in patients treated with modified Thurow appliance. Forty-five patients (22 girls and 23 boys) with skeletal Class II and angle SN.GoGn <= 35 and different maxillary patterns (n = 15), as follows: retrusive (SNA<80 degrees ), normal (SNA = 80 degrees - 84 degrees ) or protrusive (SNA>84 degrees ) maxilla; mean age 9 years at pre-treatment (T1) and 9 years and 10 months at post treatment (T2), were treated with modified Thurow cervical traction appliance, with expander screw and extraoral face bow with 10 degrees to 20 degrees fold in relation to the intraoral arch. Force of 500 gf was applied and use for 12 to 14 h/day, with fortnightly adjustments. Analysis of variance ANOVA followed by post-hoc Tukey and Kruskal-Wallis test, followed by Mann-Whitney were used (alpha = 5%). In changes obtained from stage T1 to T2, no statistically significant differences were found among the groups Protrusive, normal and retrusive maxilla for the variables SNB, SN.GoGn, 1.NA, overjet, overbite and Class II discrepancy (right and left) (p>0.05). Angular measurements SNA and ANB in the protrusive maxilla group were significantly greater than in the normal and retrusive maxilla groups (p<0.01). However, in the normal maxilla group these values did not differ significantly from those of the retrusive maxilla group (p>0.05). Within the limits of this study, it may be concluded that the modified Thurow cervical traction appliance was efficient for the correction of skeletal Class II irrespective of the maxillary pattern. The mandible had no significant rotation during treatment. PMID- 25140726 TI - F, Ca co-doped TiO2 nanocrystals with enhanced photocatalytic activity. AB - F, Ca co-doped TiO2 was synthesized by a facile one-step hydrothermal method. After doping with F, electrons can be simultaneously excited from valence band to the F doping energy level. The smaller crystal size caused by doping with Ca can exhibit more powerful redox ability and the efficient separation of photogenerated hole-electron pairs. Therefore, F, Ca co-doped TiO2 exhibited enhanced photocatalytic activity. PMID- 25140725 TI - Germ cell nuclear factor regulates gametogenesis in developing gonads. AB - Expression of germ cell nuclear factor (GCNF; Nr6a1), an orphan member of the nuclear receptor gene family of transcription factors, during gastrulation and neurulation is critical for normal embryogenesis in mice. Gcnf represses the expression of the POU-domain transcription factor Oct4 (Pou5f1) during mouse post implantation development. Although Gcnf expression is not critical for the embryonic segregation of the germ cell lineage, we found that sexually dimorphic expression of Gcnf in germ cells correlates with the expression of pluripotency associated genes, such as Oct4, Sox2, and Nanog, as well as the early meiotic marker gene Stra8. To elucidate the role of Gcnf during mouse germ cell differentiation, we generated an ex vivo Gcnf-knockdown model in combination with a regulated CreLox mutation of Gcnf. Lack of Gcnf impairs normal spermatogenesis and oogenesis in vivo, as well as the derivation of germ cells from embryonic stem cells (ESCs) in vitro. Inactivation of the Gcnf gene in vivo leads to loss of repression of Oct4 expression in both male and female gonads. PMID- 25140728 TI - Asymmetric domino reaction of cyclic N-sulfonylimines and simple aldehydes with trans-perhydroindolic acid as an organocatalyst. AB - An asymmetric domino reaction was developed utilizing readily available cyclic N sulfonylimines and simple aldehydes to construct biologically important and synthetically challenging piperidine derivatives consisting of three contiguous stereocenters. trans-Perhydroindolic acid proved to be an efficient organocatalyst in this reaction (up to 89% yield, 80:20 dr, and 99% ee). The absolute configuration of the catalytic product was determined by X-ray crystallography studies. The product could be conveniently converted to synthetically useful intermediates, such as (3R,4S)-4-ethyl-3-methyl-6 phenylpiperidinyridin-2-one (8), via a simple transformation. PMID- 25140729 TI - Assessing the combinatorial potential of the RiPP cyanobactin tru pathway. AB - Ribosomally produced natural products, the RiPPs, exhibit features that are potentially useful in the creation of large chemical libraries using simple mutagenesis. RiPPs are encoded on ribosomal precursor peptides, but they are extensively posttranslationally modified, endowing them with properties that are useful in drug discovery and biotechnology. In order to determine which mutations are acceptable, strategies are required to determine sequence selectivity independently of the context of flanking amino acids. Here, we examined the absolute sequence selectivity of the trunkamide cyanobactin pathway, tru. A series of random double and quadruple simultaneous mutants were synthesized and produced in Escherichia coli. Out of a total of 763 mutated amino acids examined in 325 unique sequences, 323 amino acids were successfully incorporated in 159 sequences, leading to >300 new compounds. Rules for tru sequence selectivity were determined, which will be useful for the design and synthesis of combinatorial biosynthetic libraries. The results are also interpreted in comparison to the known natural products of tru and pat cyanobactin pathways. PMID- 25140731 TI - Properties of lignin, cellulose, and hemicelluloses isolated from olive cake and olive stones: binding of water, oil, bile acids, and glucose. AB - A process based on a steam explosion pretreatment and alkali solution post treatment was applied to fractionate olive stones (whole and fragmented, without seeds) and olive cake into their main constitutive polymers of cellulose (C), hemicelluloses (H), and lignin (L) under optimal conditions for each fraction according to earlier works. The chemical characterization (chromatographic method and UV and IR spectroscopy) and the functional properties (water- and oil-holding capacities, bile acid binding, and glucose retardation index) of each fraction were analyzed. The in vitro studies showed a substantial bile acid binding activity in the fraction containing lignin from olive stones (L) and the alkaline extractable fraction from olive cake (Lp). Lignin bound significantly more bile acid than any other fraction and an amount similar to that bound by cholestyramine (a cholesterol-lowering, bile acid-binding drug), especially when cholic acid (CA) was tested. These results highlight the health-promoting potential of lignin from olive stones and olive cake extracted from olive byproducts. PMID- 25140732 TI - Plasmonic imaging of electrochemical oxidation of single nanoparticles. AB - Measuring electrochemical activities of nanomaterials is critical for creating novel catalysts, for developing ultrasensitive sensors, and for understanding fundamental nanoelectrochemistry. However, traditional electrochemical methods measure a large number of nanoparticles, which wash out the properties of individual nanoparticles. We report here a study of transient electrochemical oxidation of single Ag nanoparticles during collision with an electrode and voltammetry of single nanoparticles immobilized on the electrode using a plasmonic-based electrochemical current microscopy. This technique images both electrochemical reaction and size of the same individual nanoparticle, enabling quantitative examination of size-dependent electrochemical activities at single nanoparticle level. The imaging capability further allows detection of the reaction kinetics of each individual nanoparticle and analysis of the average behaviors of multiple nanoparticles. The average kinetics and size dependence can be accurately described by the Tafel equation, but there is a large variability between different nanoparticles, which underscores the importance of single nanoparticle analysis. PMID- 25140733 TI - Carba-closo-dodecaborate anions with two functional groups: [1-R-12-HC=C-closo-1 CB11H10]- (R = CN, NC, CO2H, C(O)NH2, NHC(O)H). AB - Disubstituted carba-closo-dodecaborate anions with one functional group bonded to the cluster carbon atom and one ethynyl group bonded to the antipodal boron atom were synthesized from easily accessible {closo-1-CB11} clusters. [Et4N][1-NC-12 HC=C-closo-1-CB11H10] ([Et4N]4b) was prepared starting from Cs[12-Et3SiC=C-closo 1-CB11H11] (Cs1c) via salts of the anions [1-HO(O)C-12-HC=C-closo-1-CB11H10](-) (2b) and [1-H2N(O)C-12-HC=C-closo-1-CB11H10](-) (3b). In a similar reaction sequence [Et4N][1-CN-12-HC=C-closo-1-CB11H10] ([Et4N]7b) was obtained from Cs[1 H2N-12-HC=C-closo-1-CB11H10] (Cs5b) by formamidation to yield [Et4N][1-H(O)CHN-12 HC=C-closo-1-CB11H10] ([Et4N]6b) and successive dehydration. In addition, the synthesis of the isonitrile [Et4N][1-CN-closo-1-CB11H11] ([Et4N]7a) is presented. The {closo-1-CB11} derivatives were characterized by multinuclear NMR as well as vibrational spectroscopy, mass spectrometry, and elemental analysis. The crystal structures of [Et4N][1-HO(O)C-12-HC=C-closo-1-CB11H10] ([Et4N]2b), [Et4N][1 H2N(O)C-12-HC=C-closo-1-CB11H10] ([Et4N]3b), [Et4N][1-NC-12-HC=C-closo-1-CB11H10] ([Et4N]4b), [Et4N][1-H(O)CHN-12-HC=C-closo-1-CB11H10] ([Et4N]6b), [Et4N][1-CN-12 HC=C-closo-1-CB11H10] ([Et4N]7b), and K[1-H(O)CHN-closo-1-CB11H11] ([Et4N]6a) were determined. The transmission of electronic effects through the carba-closo dodecaboron cage was studied based on (13)C NMR spectroscopic data, by results derived from density functional theory calculations, and by a comparison to the data of related benzene and bicyclo[2.2.2]octane derivatives. PMID- 25140734 TI - Enhancement of open-circuit voltage and the fill factor in CdTe nanocrystal solar cells by using interface materials. AB - Interface states influence the operation of nanocrystal (NC) solar cell carrier transport, recombination and energetic mechanisms. In a typical CdTe NC solar cell with a normal structure of a ITO/p-CdTe NCs/n-acceptor (or without)/Al configuration, the contact between the ITO and CdTe is a non-ohm contact due to a different work function (for an ITO, the value is ~4.7 eV, while for CdTe NCs, the value is ~5.3 eV), which results in an energetic barrier at the ITO/CdTe interface and decreases the performance of the NC solar cells. This work investigates how interface materials (including Au, MoO(x) and C60) affect the performance of NC solar cells. It is found that devices with interface materials have shown higher V(oc) than those without interface materials. For the case in which we used Au as an interface, we obtained a high open-circuit voltage of 0.65 V, coupled with a high fill factor (62%); this resulted in a higher energy conversion efficiency (ECE) of 5.3%, which showed a 30% increase in the ECE compared with those without the interlayer. The capacitance measurements indicate that the increased V(oc) in the case in which Au was used as the interface is likely due to good ohm contact between the Au's and the CdTe NCs' thin film, which decreases the energetic barrier at the ITO/CdTe interface. PMID- 25140735 TI - Multifunctional cyclotriphosphazene/hexagonal boron nitride hybrids and their flame retarding bismaleimide resins with high thermal conductivity and thermal stability. AB - A novel hybridized multifunctional filler (CPBN), cyclotriphosphazene/hexagonal boron nitride (hBN) hybrid, was synthesized by chemically coating hBN with hexachlorocyclotriphosphazene and p-phenylenediamine, its structure was systemically characterized. Besides, CPBN was used to develop new flame retarding bismaleimide/o,o'-diallylbisphenol A (BD) resins with simultaneously high thermal conductivity and thermal stability. The nature of CPBN has a strong influence on the flame behavior of the composites. With the addition of only 5 wt % CPBN to BD resin, the thermal conductivity increases 2 times; meanwhile the flame retardancy of BD resin is remarkably increased, reflected by the increased limited oxygen index, much longer time to ignition, significantly reduced heat release rate. The thermogravimetric kinetics, structures of chars and pyrolysis gases, and cone calorimeter tests were investigated to reveal the unique flame retarding mechanism of CPBN/BD composites. CPBN provides multieffects on improving the flame retardancy, especially in forming a protective char layer, which means a more thermally stable and condensed barrier for heat and mass transfer, and thus protecting the resin from further combustion. PMID- 25140736 TI - Identification of genetic variants associated with alternative splicing using sQTLseekeR. AB - Identification of genetic variants affecting splicing in RNA sequencing population studies is still in its infancy. Splicing phenotype is more complex than gene expression and ought to be treated as a multivariate phenotype to be recapitulated completely. Here we represent the splicing pattern of a gene as the distribution of the relative abundances of a gene's alternative transcript isoforms. We develop a statistical framework that uses a distance-based approach to compute the variability of splicing ratios across observations, and a non parametric analogue to multivariate analysis of variance. We implement this approach in the R package sQTLseekeR and use it to analyze RNA-Seq data from the Geuvadis project in 465 individuals. We identify hundreds of single nucleotide polymorphisms (SNPs) as splicing QTLs (sQTLs), including some falling in genome wide association study SNPs. By developing the appropriate metrics, we show that sQTLseekeR compares favorably with existing methods that rely on univariate approaches, predicting variants that behave as expected from mutations affecting splicing. PMID- 25140739 TI - Classical and non-classical redox reactions of Pd(II) complexes containing redox active ligands. AB - Reactivity studies of a Pd(II)-verdazyl complex reveal novel ligand-centred reduction processes which trigger pseudo-reductive elimination at Pd. Reaction of the complex with water induces a ligand-centred redox disproportionation. The reduced verdazyl ligands can also be reversibly protonated. PMID- 25140738 TI - Large sample area and size are needed for forest soil seed bank studies to ensure low discrepancy with standing vegetation. AB - A large number of small-sized samples invariably shows that woody species are absent from forest soil seed banks, leading to a large discrepancy with the seedling bank on the forest floor. We ask: 1) Does this conventional sampling strategy limit the detection of seeds of woody species? 2) Are large sample areas and sample sizes needed for higher recovery of seeds of woody species? We collected 100 samples that were 10 cm (length) * 10 cm (width) * 10 cm (depth), referred to as larger number of small-sized samples (LNSS) in a 1 ha forest plot, and placed them to germinate in a greenhouse, and collected 30 samples that were 1 m * 1 m * 10 cm, referred to as small number of large-sized samples (SNLS) and placed them (10 each) in a nearby secondary forest, shrub land and grass land. Only 15.7% of woody plant species of the forest stand were detected by the 100 LNSS, contrasting with 22.9%, 37.3% and 20.5% woody plant species being detected by SNLS in the secondary forest, shrub land and grassland, respectively. The increased number of species vs. sampled areas confirmed power-law relationships for forest stand, the LNSS and SNLS at all three recipient sites. Our results, although based on one forest, indicate that conventional LNSS did not yield a high percentage of detection for woody species, but SNLS strategy yielded a higher percentage of detection for woody species in the seed bank if samples were exposed to a better field germination environment. A 4 m2 minimum sample area derived from power equations is larger than the sampled area in most studies in the literature. Increased sample size also is needed to obtain an increased sample area if the number of samples is to remain relatively low. PMID- 25140737 TI - The cellular bromodomain protein Brd4 has multiple functions in E2-mediated papillomavirus transcription activation. AB - The cellular bromodomain protein Brd4 functions in multiple processes of the papillomavirus life cycle, including viral replication, genome maintenance, and gene transcription through its interaction with the viral protein, E2. However, the mechanisms by which E2 and Brd4 activate viral transcription are still not completely understood. In this study, we show that recruitment of positive transcription elongation factor b (P-TEFb), a functional interaction partner of Brd4 in transcription activation, is important for E2's transcription activation activity. Furthermore, chromatin immunoprecipitation (ChIP) analyses demonstrate that P-TEFb is recruited to the actual papillomavirus episomes. We also show that E2's interaction with cellular chromatin through Brd4 correlates with its papillomavirus transcription activation function since JQ1(+), a bromodomain inhibitor that efficiently dissociates E2-Brd4 complexes from chromatin, potently reduces papillomavirus transcription. Our study identifies a specific function of Brd4 in papillomavirus gene transcription and highlights the potential use of bromodomain inhibitors as a method to disrupt the human papillomavirus (HPV) life cycle. PMID- 25140740 TI - Hydrocarbons emitted by waggle-dancing honey bees increase forager recruitment by stimulating dancing. AB - Hydrocarbons emitted by waggle-dancing honey bees are known to reactivate experienced foragers to visit known food sources. This study investigates whether these hydrocarbons also increase waggle-dance recruitment by observing recruitment and dancing behavior when the dance compounds are introduced into the hive. If the hydrocarbons emitted by waggle-dancing bees affect the recruitment of foragers to a food source, then the number of recruits arriving at a food source should be greater after introduction of dance compounds versus a pure solvent control. This prediction was supported by the results of experiments in which recruits were captured at a feeder following introduction of dance compounds into a hive. This study also tested two nonexclusive behavioral mechanism(s) by which the compounds might stimulate recruitment; 1) increased recruitment could occur by means of increasing the recruitment effectiveness of each dance and/or 2) increased recruitment could occur by increasing the intensity of waggle-dancing. These hypotheses were tested by examining video records of the dancing and recruitment behavior of individually marked bees following dance-compound introduction. Comparisons of numbers of dance followers and numbers of recruits per dance and waggle run showed no significant differences between dance-compound and solvent-control introduction, thus providing no support for the first hypothesis. Comparison of the number of waggle dance bouts and the number of waggle runs revealed significantly more dancing during morning dance-compound introduction than morning solvent-control introduction, supporting the second hypothesis. These results suggest that the waggle-dance hydrocarbons play an important role in honey bee foraging recruitment by stimulating foragers to perform waggle dances following periods of inactivity. PMID- 25140742 TI - Critical-care pain observation tool in critically ill patients. PMID- 25140741 TI - A culture of respect: champions and models. PMID- 25140743 TI - Move to improve: progressive mobility in the intensive care unit. AB - Bed rest has detrimental consequences, and therefore in the ICU, progressive early mobility should be the goal for every patient expected to survive. This article examines the consequences of immobility, barriers experienced when attempting to increase patients' mobility, and ways in which dedicated mobility teams can overcome these barriers. PMID- 25140744 TI - Where do you want to give report? AB - Traditionally, nurses have met in a conference room to give each other end-of shift report. Many hospitals are now moving to bedside report. Which does the research support as best practice? What are the ethical and practical issues of each? This article answers those questions. PMID- 25140745 TI - Model for heart failure education. AB - Heart failure (HF) is the heart's inability to meet the body's need for blood and oxygen. According to the American Heart Association 2013 update, approximately 5.1 million people are diagnosed with HF in the United States in 2006. Heart failure is the most common diagnosis for hospitalization. In the United States, the HF direct and indirect costs are estimated to be US $39.2 billion in 2010. To address this issue, nursing educators designed innovative teaching frameworks on HF management both in academia and in clinical settings. The model was based on 2 resources: the American Association of Heart Failure Nurses (2012) national nursing certification and the award-winning Pierce County Responsive Care Coordination Program. The HF educational program is divided into 4 modules. The initial modules offer foundational levels of Bloom's Taxonomy then progress to incorporate higher-levels of learning when modules 3 and 4 are reached. The applicability of the key components within each module allows formatting to enhance learning in all areas of nursing, from the emergency department to intensive care units to the medical-surgical step-down units. Also applicable would be to provide specific aspects of the modules to nurses who care for HF patients in skilled nursing facility, rehabilitation centers, and in the home health care setting. PMID- 25140746 TI - Cardiac comorbidities and sexual activity predict sexual self-perception and adjustment. AB - BACKGROUND: Changes in sexual satisfaction and sexual activity are often reported by cardiac patients, although factors influencing sexual adjustment are not well established. Knowledge of risk and protective factors can guide nurses in addressing physical and psychological needs of patients. OBJECTIVES: We examined predictors of sexual self-perception and adjustment in a cross section of cardiac patients. METHODS: A nonexperimental, descriptive survey design was used to examine overall sexual self-perception and adjustment, sexual anxiety, sexual depression, sexual satisfaction, sexual self-efficacy, sexual activity, selected demographic factors, and 20 cardiac and noncardiac comorbidities using a mailed survey with a broad sampling of cardiac patients (n = 128). Data were analyzed with descriptive statistics, t tests, and regression analysis. RESULTS: Fewer cardiac conditions and being sexually active were significant predictors of sexual self-perception and adjustment. Participants with hypertension reported more sexual depression; those with myocardial infarction had higher scores for both sexual anxiety and depression, and greater sexual anxiety occurred for those with peripheral artery leg bypass. DISCUSSION: Positive sexual self-perception and adjustment are linked to sexual activity and fewer cardiac problems. This finding can be used to inform decisions about initiating sexual counseling. PMID- 25140748 TI - Incivility among intensive care nurses: the effects of an educational intervention. AB - BACKGROUND: Incivility is a significant problem in nurse satisfaction and nurse retention and can be detrimental to a patient's outcome; therefore, it would be beneficial to educate nurses on ways to improve incivility in clinical practice. OBJECTIVES: To determine if a nursing education program, utilizing case studies and discussion of the nurses' experiences would increase awareness of incivility and impact the number of perceived incidences by (1) assessing nurses' experience of incivility along with discerning the perceived source of the incivility and (2) educating the nurses, thus determining if the in-service education decreases the incidence of incivility in the adult intensive care unit. METHODS: This is a quantitative pilot study that utilized a 1-group preintervention and postintervention test design. The intervention was a 60-minute educational program. Twenty-one nurses completed the survey that assesses prevalence of incivility by specific sources, such as nurses, physicians, supervisors, general (other hospital employees), and patients before and after participation in the education intervention. Descriptive statistics of the 5 dimensions of civility and a total dimension score of civility were used. RESULTS: A total of 21 nurses completed all parts of this study. The postintervention score had a higher mean than the preintervention score in each of the dimensions. Higher scores indicate incivility; thus, lower scores indicate civility. Therefore, more instances of incivility were identified after intervention to increase awareness of incivility. In addition, nurses perceived greater amounts of incivility from patients and families, whereas the direct supervisor (team leaders) showed the greatest amount of civility. A hierarchical regression revealed that race had the largest negative impact, followed by nurses practicing for more than 5 years, part-time status, and younger age, respectively. DISCUSSION: The outcomes in this pilot study contradict much of the research on incivility in nursing, which previously found that supervisors are more uncivil toward their staff nurses than the rest of the staff. The results of the current study found that incivility perceptions were higher in the postintervention survey; these findings suggest that the education was effective, thus creating more awareness of incivility. This could be a positive cultural turning point in nursing as it decreases incivility, which in turn will help to decrease medical errors, attrition rates, and the financial burden on hospitals. PMID- 25140751 TI - Design, synthesis and biological characterization of thiazolidin-4-one derivatives as promising inhibitors of Toxoplasma gondii. AB - We designed and synthesized a large number of novel thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii activity. This scaffold was functionalized at the N1-hydrazine portion with aliphatic, cycloaliphatic and (hetero)aromatic moieties. Then, a benzyl pendant was introduced at the lactamic NH of the core nucleus to evaluate the influence of this chemical modification on biological activity. The compounds were subjected to several in vitro assays to assess their anti-parasitic efficacy, cytotoxicity on fibroblasts, inhibition of tachyzoite invasion/attachment and replication after treatment. Results showed that fourteen of these thiazole-based compounds compare favorably to control compound trimethoprim in terms of parasite growth inhibition. PMID- 25140752 TI - Discovery of Troger's base analogues as selective inhibitors against human breast cancer cell line: design, synthesis and cytotoxic evaluation. AB - A library of structurally diverse Troger's base analogues has been constructed via unusual amination of methylene bridge employing Vilsmeier-Haack conditions as well as by the incorporation of five and six membered heterocycles on the aromatic core of Troger's base framework. The constructed structurally diverse frameworks were evaluated for their cytotoxic activities against a panel of three human cancer lines A549 (lung adenocarcinoma), MDAMB-231 (breast) and SK-N-SH (neuroblastoma). From the activity profile obtained, a redesign of Troger's base analogues led to the construction of more potent molecular entities. The study led to development of a series of compounds with MDAMB-231 cell line specific cytotoxicity. Of the 30 compounds synthesized and evaluated, 7 compounds were found to possess cytotoxicity that is equivalent or better than standard drug doxorubicin against MDAMB-231 cell line while only one compound was found to be active against SK-N-SH cell line. PMID- 25140753 TI - Hierarchical self-assembly of 'hard-soft' Janus particles into colloidal molecules and larger supracolloidal structures. AB - Here we report the self-assembly of 'hard-soft' micron-sized Janus particles into clusters in aqueous media. The assembly process is induced by the desorption of a polymeric stabiliser from the particles, that is polyvinylpyrrolidone (PVP). Upon contact through collision and coalescence of the soft polymeric lobes, the newly formed clusters adopt a minimized surface area to volume ratio, thereby forming distinct microscopic supracolloidal analogues of simple molecular valance shell electron pair repulsion (VSEPR) space-fill structures. To explain this behaviour, the colloidal stability of our particle suspensions were studied with and without an adsorbed steric surfactant. Simulations of expected cluster morphology, compared with those from cryo-SEM analysis support the mechanism of assembly driven by surface area minimization in the case of soft-soft interactions. Altering the soft lobe size with respect to the hard lobe indicates a moderate effect on number of primary particles per cluster. Additionally, higher order structures of clusters containing a number of primary particles exceeding what is possible for a 'solid' core cluster are observed. As such, we also investigated the formation of suprastructures using a high number of 'hard-soft' Janus particles and verified their effective Pickering stabilization of air bubbles. PMID- 25140755 TI - Patient safety still lagging: advocates call for national patient safety monitoring board. PMID- 25140754 TI - The role of arginase and rho kinase in cardioprotection from remote ischemic perconditioning in non-diabetic and diabetic rat in vivo. AB - BACKGROUND: Pharmacological inhibition of arginase and remote ischemic perconditioning (RIPerc) are known to protect the heart against ischemia/reperfusion (IR) injury. PURPOSE: The objective of this study was to investigate whether (1) peroxynitrite-mediated RhoA/Rho associated kinase (ROCK) signaling pathway contributes to arginase upregulation following myocardial IR; (2) the inhibition of this pathway is involved as a cardioprotective mechanism of remote ischemic perconditioning and (3) the influence of diabetes on these mechanisms. METHODS: Anesthetized rats were subjected to 30 min left coronary artery ligation followed by 2 h reperfusion and included in two protocols. In protocol 1 rats were randomized to 1) control IR, 2) RIPerc induced by bilateral femoral artery occlusion for 15 min during myocardial ischemia, 3) RIPerc and administration of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L NMMA), 4) administration of the ROCK inhibitor hydroxyfasudil or 5) the peroxynitrite decomposition catalyst FeTPPS. In protocol 2 non-diabetic and type 1 diabetic rats were randomosed to IR or RIPerc as described above. RESULTS: Infarct size was significantly reduced in rats treated with FeTPPS, hydroxyfasudil and RIPerc compared to controls (P<0.001). FeTPPS attenuated both ROCK and arginase activity (P<0.001 vs. control). Similarly, RIPerc reduced arginase and ROCK activity, peroxynitrite formation and enhanced phospho-eNOS expression (P<0.05 vs. control). The cardioprotective effect of RIPerc was abolished by L-NMMA. The protective effect of RIPerc and its associated changes in arginase and ROCK activity were abolished in diabetes. CONCLUSION: Arginase is activated by peroxynitrite/ROCK signaling cascade in myocardial IR. RIPerc protects against IR injury via a mechanism involving inhibition of this pathway and enhanced eNOS activation. The beneficial effect and associated molecular changes of RIPerc is abolished in type 1 diabetes. PMID- 25140756 TI - Near-infrared Raman spectroscopy for assessing biochemical changes of cervical tissue associated with precarcinogenic transformation. AB - Raman spectroscopy measures the inelastically scattered light from tissue that is capable of identifying native tissue biochemical constituents and their changes associated with disease transformation. This study aims to characterize the Raman spectroscopic properties of cervical tissue associated with the multi-stage progression of cervical precarcinogenic sequence. A rapid-acquisition fiber-optic near-infrared (NIR) Raman diagnostic system was employed for tissue Raman spectral measurements at 785 nm excitation. A total of 68 Raman spectra (23 benign, 29 low-grade squamous intraepithelial lesions (LSIL) and 16 high grade squamous intraepithelial lesions (HSIL)) were measured from 25 cervical tissue biopsy specimens, as confirmed by colposcopy-histopathology. The semi quantitative biochemical modeling based on the major biochemicals (i.e., DNA, proteins (histone, collagen), lipid (triolein) and carbohydrates (glycogen)) in cervical tissue uncovers the stepwise accumulation of biomolecular changes associated with progressive cervical precarcinogenesis. Multi-class partial least squares-discriminant analysis (PLS-DA) together with leave-one tissue site-out, cross-validation yielded the diagnostic sensitivities of 95.7%, 82.8% and 81.3%; specificities of 100.0%, 92.3% and 88.5%,for discrimination among benign, LSIL and HSIL cervical tissues, respectively. This work suggests that the Raman spectral biomarkers have identified the potential to be used for monitoring the multi-stage cervical precarcinogenesis, forming the foundation of applying NIR Raman spectroscopy for the early diagnosis of cervical precancer in vivo at the molecular level. PMID- 25140757 TI - Endometriosis associated with relapsing ascites and pleural effusions. PMID- 25140758 TI - Effect of Ganoderma applanatum mycelium extract on the inhibition of adipogenesis in 3T3-L1 adipocytes. AB - Ganoderma applanatum (GA) and related fungal species have been used for over 2000 years in China to prevent and treat various human diseases. However, there is no critical research evaluating the functionality of GA grown using submerged culture technology. This study aimed to evaluate the effects of submerged culture GA mycelium (GAM) and its active components (protocatechualdehyde [PCA]) on preadipocyte differentiation of 3T3-L1 cells. Mouse-derived preadipocyte 3T3-L1 cells were treated with differentiation inducers in the presence or absence of GAM extracts. We determined triglyceride accumulations, glycerol-3-phosphate dehydrogenase (GPDH) activities, and differentiation makers. PCA, the active component of GAM extract, was also used to treat 3T3-L1 cells. The MTT assay showed that the GAM extract (0.01-1 mg/mL) was not toxic to 3T3-L1 preadipocyte. Treatment of cells with GAM extracts and its active components significantly decreased the GPDH activity and lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. Western blot analysis results showed that the protein expression levels of peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT/enhancer-binding protein alpha (C/EBPalpha), and sterol regulatory element-binding protein 1 (SREBP1) were inhibited by the GAM extract. In addition, adipogenic-specific genes such as perilipin, fatty acid synthase (FAS), fatty acid transport protein 1 (FATP1), and fatty acid-binding protein 4 (FABP4) decreased in a dose-dependent manner. Quantitative high-performance liquid chromatography analysis showed that the GAM extract contained 1.14 mg/g PCA. GAM extracts suppressed differentiation of 3T3-L1 preadipocytes, in part, through altered regulation of PPARgamma, C/EBPalpha, and SREBP1. These results suggest that GAM extracts and PCA may suppress adipogenesis by inhibiting differentiation of preadipocytes. PMID- 25140761 TI - Anti-inflammatory effects of ethanolic extract from Sargassum horneri (Turner) C. Agardh on lipopolysaccharide-stimulated macrophage activation via NF-kappaB pathway regulation. AB - Inflammation is major symptom of the innate immune response by infection of microbes. Macrophages, one of immune response related cells, play a role in inflammatory response. Recent studies reported that various natural products can regulate the activation of immune cells such as macrophage. Sargassum horneri (Turner) C. Agardh is one of brown algae. Recently, various seaweeds including brown algae have antioxidant and anti-inflammatory effects. However, anti inflammatory effects of Sargassum horneri (Turner) C. Agardh are still unknown. In this study, we investigated anti-inflammatory effects of ethanolic extract of Sargassum horneri (Turner) C. Agardh (ESH) on RAW 264.7 murine macrophage cell line. The ESH was extracted from dried Sargassum horneri (Turner) C. Agardh with 70% ethanol and then lyophilized at -40 degrees C. ESH was not cytotoxic to RAW 264.7, and nitric oxide (NO) production induced by LPS-stimulated macrophage activation was significantly decreased by the addition of 200 MUg/mL of ESH. Moreover, ESH treatment reduced mRNA level of cytokines, including IL-1beta, and pro-inflammatory genes such as iNOS and COX-2 in LPS-stimulated macrophage activation in a dose-dependent manner. ESH was found to elicit anti-inflammatory effects by inhibiting ERK, p-p38 and NF-kappaB phosphorylation. In addition, ESH inhibited the release of IL-1beta in LPS-stimulated macrophages. These results suggest that ESH elicits anti-inflammatory effects on LPS-stimulated macrophage activation via the inhibition of ERK, p-p38, NF-kappaB, and pro-inflammatory gene expression. PMID- 25140759 TI - Psychometric assessment of the craving to tan questionnaire. AB - BACKGROUND: Researchers and clinicians suggest that excessive tanning may be a behavioral addiction. Given the significance of craving in substance use, craving may be a useful construct to assess in those who tan. OBJECTIVE: We designed this study to assess the psychometric properties of an alcohol craving measure adapted to measure past-week craving to tan. METHODS: Undergraduate students (n = 421) who reported past-month tanning completed a battery of questionnaires that assessed demographics, tanning-related characteristics, and psychopathology, in addition to the Craving to Tan Questionnaire (CTQ). RESULTS: Analyses provided support for a single factor CTQ with good internal consistency, construct validity and convergent validity. CTQ scores were significantly higher among problematic versus non-problematic and dependent versus non-dependent tanners. CTQ scores were also associated with several tanning-related characteristics, such money spent on tanning in a typical month, frequency of tanning, and frequency of tanning-related problems. Additional analyses found that past-week craving to tan was significantly associated with greater obsessive compulsive and body dysmorphic symptoms. CONCLUSIONS: It may be useful in clinical settings to identify those experiencing problems with tanning and in research to further clarify the conceptualization of addiction-like tanning. However, the CTQ needs further evaluation. PMID- 25140762 TI - Impact of 5-h phase advance on sleep architecture and physical performance in athletes. AB - Travel across time zones causes jet lag and is accompanied by deleterious effects on sleep and performance in athletes. These poor performances have been evaluated in field studies but not in laboratory conditions. The purpose of this study was to evaluate, in athletes, the impact of 5-h phase advance on the architecture of sleep and physical performances (Wingate test). In a sleep laboratory, 16 male athletes (age: 22.2 +/- 1.7 years, height: 178.3 +/- 5.6 cm, body mass: 73.6 +/- 7.9 kg) spent 1 night in baseline condition and 2 nights, 1 week apart, in phase shift condition recorded by electroencephalography to calculate sleep architecture variables. For these last 2 nights, the clock was advanced by 5 h. Core body temperature rhythm was assessed continuously. The first night with phase advance decreased total sleep time, sleep efficiency, sleep onset latency, stage 2 of nonrapid eye movement (N2), and rapid eye movement (REM) sleep compared with baseline condition, whereas the second night decreased N2 and increased slow-wave sleep and REM, thus improving the quality of sleep. After phase advance, mean power improved, which resulted in higher lactatemia. Acrophase and bathyphase of temperature occurred earlier and amplitude decreased in phase advance but the period was not modified. These results suggest that a simulated phase shift contributed to the changes in sleep architecture, but did not significantly impair physical performances in relation with early phase adjustment of temperature to the new local time. PMID- 25140764 TI - Structural insights of JAK2 inhibitors: pharmacophore modeling and ligand-based 3D-QSAR studies of pyrido-indole derivatives. AB - In this study we have performed pharmacophore modeling and built a 3D QSAR model for pyrido-indole derivatives as Janus Kinase 2 inhibitors. An efficient pharmacophore has been identified from a data set of 51 molecules and the identified pharmacophore hypothesis consisted of one hydrogen bond acceptor, two hydrogen bond donors and three aromatic rings, i.e. ADDRRR. A powerful 3D-QSAR model has also been constructed by employing Partial Least Square regression analysis with a regression coefficient of 0.97 (R(2)) and Q(2) of 0.95, and Pearson-R of 0.98. PMID- 25140765 TI - A Noncausal Relation Between Casual Sex in Adolescence and Early Adult Depression and Suicidal Ideation: A Longitudinal Discordant Twin Study. AB - Research on relations between casual sex and mental health is inconclusive; while some studies indicate casual sex may lead to more negative mental health (e.g., depression), other studies report no such relationship. Using a genetically informed approach, this study examined whether earlier casual sex (i.e., ever engaging in casual sex and number of casual sex partners) in adolescence has a causal influence on later mental health in young adulthood (i.e., depressive symptoms and suicidal ideation), as well as the reverse relationship (adolescent negative mental health on young adult casual sex) by exploiting the quasi experimental nature of discordant-twin models. Multilevel models that measured within-twin and between-twin pair effects of adolescent casual sex were estimated, using 714 twins (357 twin pairs) from the sibling subsample of the National Longitudinal Study of Adolescent Health (Add Health). Results indicated that there was no causal relationship between casual sex in adolescence and higher levels of depressive symptoms or suicidal ideation in young adulthood, and these effects did not differ by gender. There were also no causal relations between adolescent depressive symptoms or suicidal ideation and casual sexual experience in young adulthood. Implications for ways to increase scientific rigor by using different methods (e.g., genetically informed analyses) are discussed. PMID- 25140763 TI - Influence of HMB supplementation and resistance training on cytokine responses to resistance exercise. AB - PURPOSE: The purpose of this study was to determine the effects of a multinutritional supplement including amino acids, beta-hydroxy-beta methylbutyrate (HMB), and carbohydrates on cytokine responses to resistance exercise and training. METHODS: Seventeen healthy, college-aged men were randomly assigned to a Muscle ArmorTM (MA; Abbott Nutrition, Columbus, OH) or placebo supplement group and 12 weeks of resistance training. An acute resistance exercise protocol was administered at 0, 6, and 12 weeks of training. Venous blood samples at pre-, immediately post-, and 30-minutes postexercise were analyzed via bead multiplex immunoassay for 17 cytokines. RESULTS: After 12 weeks of training, the MA group exhibited decreased interferon-gamma (IFN-gamma) and interleukin (IL)-10. IL-1beta differed by group at various times. Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-7, IL-8, IL-12p70, IL-13, IL-17, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 beta (MIP-1beta) changed over the 12-week training period but did not differ by group. CONCLUSIONS: Twelve weeks of resistance training alters the cytokine response to acute resistance exercise, and supplementation with HMB and amino acids appears to further augment this result. PMID- 25140766 TI - [Risk factors for invasive pulmonary fungal infection in children]. AB - OBJECTIVE: To analyze the risk factors for invasive pulmonary fungal infection (IPFI) and to provide a theoretical basis for the early prevention and treatment of IPFI. METHODS: A retrospective case-control study was conducted on the clinical data of children hospitalized in the pediatric intensive care unit between January 2012 and March 2013. These children consisted of 48 patients with a clinical diagnosis of IPFI (IPFI group) and 106 pneumonia patients without a clinical diagnosis of IPFI (non-IPFI group). The clinical date of the two groups were compared and analyzed. The main risk factors for the development of IPIF were identified by unconditional multivariate logistic regression analysis. RESULTS: Compared with the non-IPIF group, the IPIF group had significantly lower mean age and serum albumin level (P<0.01), significantly longer mean length of hospital stay, duration of antibiotic use, and duration of corticosteroid use (P<0.01), and significantly higher rates of malnutrition, invasive mechanical ventilation, indwelling catheter use, oropharyngeal fungal infection, and diarrhea (P<0.05). Multivariate logistic regression analysis showed that invasive mechanical ventilation, diarrhea, long duration of corticosteroid use, long duration of antibiotic use, young age, and low serum albumin level were independent risk factors for the development of IPFI. CONCLUSIONS: For the infants with suspected IPFI for whom pathogenic examination is difficult to perform, IPFI should be considered in cases of invasive mechanical ventilation, diarrhea, long-time uses of broad-spectrum antibiotics and corticosteroids and hypoalbuminemia, and empirical antifungal therapy should be performed as soon as possible. PMID- 25140767 TI - [Risk factors for pleural lung disease in children with juvenile idiopathic arthritis]. AB - OBJECTIVE: To investigate the risk factors for pleural lung disease (PLD) in children with juvenile idiopathic arthritis (JIA) and to provide a basis for the early diagnosis and timely treatment of this disease. METHODS: A total of 360 children with a confirmed diagnosis of JIA were enrolled, and their clinical data were retrospectively analyzed. All patients underwent a chest X-ray. The patients with PLD were assigned to PLD group, while those without PLD were assigned to non PLD group. The clinical, imaging, and laboratory results of JIA patients with PLD were analyzed. RESULTS: Among the 360 JIA patients, 43 (11.9%) had PLD, and 9 (21%) of them had respiratory symptoms. Chest X-ray findings mainly included interstitial pneumonitis (53.5%) and pleurisy and/or pleural effusion (38.1%). In the 43 cases of JIA-PLD, 4 (9.3%) had normal chest X-ray findings but abnormal chest CT findings. The incidence of PLD was relatively high in patients aged under 3 years and those aged 12 years or above. Children with systemic JIA had a relatively high incidence of PLD. Compared with the non-PLD group, the PLD group had a significantly higher incidence of anemia, elevated white blood cell (WBC) count and IgG levels in peripheral blood, and positive rheumatoid factors or antinuclear antibodies (P<0.05). CONCLUSIONS: Among children with JIA, PLD is mostly seen in patients with systemic JIA or aged <3 years or >= 12 years, especially those with anemia, elevated WBC count and IgG levels, and positive rheumatoid factors or antinuclear antibodies. For JIA patients with PLD, interstitial pneumonitis is usually seen on chest X-ray or CT, but respiratory symptoms are rarely observed. Routine use of high-resolution chest CT is recommended for early diagnosis and timely treatment of PLD in children with JIA. PMID- 25140768 TI - [Pathogenic analysis of ventilator-associated pneumonia in the pediatric intensive care unit in high-altitude areas]. AB - OBJECTIVE: To investigate the pathogens of ventilator-associated pneumonia (VAP) and their drug resistance in the pediatric intensive care unit (PICU) in high altitude areas and to provide a clinical basis for the prevention and treatment of VAP. METHODS: A total of 94 children with VAP hospitalized in the PICU in high altitude areas between June 2011 and June 2013 were recruited. Their lower respiratory tract secretions were collected for bacterial culture and drug sensitivity test. RESULTS: Of the 94 children with VAP, 22 (23%) had a single bacterial infection, and 72 (77%) had mixed infections, mostly with Klebsiella pneumoniae and Acinetobacter baumannii (17 cases, 27%). Of the 178 isolated strains of pathogens, 139 (78%) were Gram-negative bacteria (G- bacteria), mainly including Klebsiella pneumoniae, Stenotrophomonas maltophilia, Acinetobacter baumannii, and Pseudomonas aeruginosa, 26 (15%) were Gram-positive bacteria (G+ bacteria), mainly including Staphylococcus aureus, and 13 (7%) were fungi, mainly including Candida albicans. Most G- bacteria had a high drug resistance. Pseudomonas aeruginosa was extensively drug-resistant. Acinetobacter baumannii was only highly sensitive to cefoperazone/sulbactam and imipenem. Multidrug resistance (methicillin resistance) was found in G+ bacteria, for which vancomycin was effective. CONCLUSIONS: The pathogens of VAP in high-altitude areas are mostly G- bacteria, which may cause mixed infections and develop drug resistance. This provides guidance for the rational use of antimicrobial drugs and the development of key prevention and control measures for VAP. PMID- 25140769 TI - [Values of a combination of multiple less invasive or non-invasive examinations in the diagnosis of pediatric sputum-negative pulmonary tuberculosis]. AB - OBJECTIVE: To study the values of a combination of multiple less invasive or non invasive examinations including chest computed tomography (CT) scan, purified protein derivative (PPD) test, erythrocyte sedimentation rate (ESR) test, and C reactive protein (CRP) test in the diagnosis of pediatric sputum-negative pulmonary tuberculosis (TB). METHODS: A retrospective analysis was performed on the clinical data of 269 children with confirmed pulmonary TB. Clinical symptoms and test results were analyzed and compared between the sputum-negative group (161 patients) and the sputum-positive group (108 patients). RESULTS: The sputum negative group had atypical clinical symptoms, with fewer typical or relatively specific imaging features compared with the sputum-positive group. The positive rates of PPD, ESR, and CRP tests for the sputum-negative group were 39.1%, 44.1%, and 56.5%, respectively, versus 55.6%, 79.6%, and 59.3% for the sputum-positive group. There were significant differences in the positive rates of PPD and ESR tests between the two groups (P<0.05). More than 80% of the patients in each group were diagnosed with pulmonary TB according to three or four less invasive or non-invasive tests, without significant difference in the positive rate between the two groups (P>0.05). Forty-six patients in the sputum-negative group underwent bronchoscopy, and morphological changes with a diagnostic value and/or etiological and pathological evidence were observed in 40 (87.0%) of them. CONCLUSIONS: The diagnosis rate of pediatric sputum-negative pulmonary TB can be increased by combining tests including chest CT scan, PPD test, ESR test, and CRP test. Bronchoscopy is a reliable method for the auxiliary diagnosis of pediatric sputum-negative pulmonary TB if the combining tests cannot provide compelling evidence. PMID- 25140770 TI - [Application of asthma predictive index-based group therapy in wheezing children under 5 years of age]. AB - OBJECTIVE: To study the application value of asthma predictive index (API)-based group therapy in wheezing children under 5 years of age. METHODS: A total of 239 wheezing children under 5 years of age were divided into API-positive (n=126) and API-negative groups (n=113). Each group was randomly assigned to inhaled corticosteroids (ICS) subgroup and montelukast sodium (leukotriene receptor antagonist, LTRA) subgroup. The ICS and LTRA subgroups received the same drug therapy at the same dosage within the first four weeks of treatment. In the stable period of disease, the ICS subgroup only received aerosol inhalation of budesonide suspension, while the LTRA group was orally given montelukast sodium only. Asthma symptom scores were assessed and recorded at different time points. RESULTS: In the first four weeks of treatment, ICS and LTRA were effective both in the API-positive and API-negative groups; the two groups showed significant improvements in asthma symptom scores, and the asthma symptom score showed no significant difference between the ICS and LTRA subgroups of each group. After 24 weeks of treatment, the two therapies were still effective; in the API-positive group, the LTRA subgroup had a better treatment outcome than the ICS subgroup, but there was no significant difference in treatment outcome between the LTRA and ICS subgroups of the API-negative group. CONCLUSIONS: For wheezing children under 5 years of age, therapeutic strategies can be chosen based on API in the stable period of disease, so as to better control wheezing. PMID- 25140771 TI - [Clinical application of tidal breathing lung function test in 1-4 years old children with wheezing diseases]. AB - OBJECTIVE: To study the clinical significance of tidal breathing lung function test in 1-4 years old children with wheezing diseases. METHODS: A total of 141 1 4 years old children with wheezing diseases were enrolled as the observed groups (41 cases of asthma, 54 cases of asthmatic bronchitis, and 46 cases of bronchopneumonia). Thirty children without respiratory diseases were enrolled as the control group. All the recruits underwent tidal breathing lung function test. The observed groups underwent bronchial dilation test, and tidal breathing flow volume (TBFV) parameters were evaluated before and after bronchial dilation test. RESULTS: The observed groups showed obstructive ventilatory disorder (65%) according to the TBFV loop, and their ratio of time to peak tidal expiratory flow (TPTEF) to total expiratory time (TE) and ratio of volume to peak expiratory flow (VPEF) to total expiratory volume (VE) were significantly lower than in the control group (P<0.05). The asthma subgroup had significantly improved TPTEF/TE and VPEF/VE after bronchial dilation test (P<0.05). Taking an improvement rate of >= 15% either for TPTEF/TE or for VPEF/VE as an indicator of positive bronchial dilation test, the bronchial dilation test had a sensitivity of 47% and a specificity of 84% in diagnosing asthma in 1-4 years old children. The positive rate was 28% among the children in the asthma subgroup with an TPTEF/TE ratio of >= 23% before bronchial dilation test, versus 65% in those with an TPTEF/TE ratio of <23%. CONCLUSIONS: Obstructive ventilatory disorder is the main impairment of tidal breathing lung function in 1-4 years old children with wheezing diseases. Tidal breathing bronchial dilation test can reflect a reversal of airway obstruction to a certain extent. The sensitivity of bronchial dilation test for the diagnosis of asthma is not satisfactory in 1-4 years old children with wheezing diseases, but this test has a relatively high diagnostic value in children with severe airway obstruction. PMID- 25140773 TI - [Expression of TGF-beta1 and PAI-1 in premature infants with bronchopulmonary dysplasia]. AB - OBJECTIVE: To study the expression of transforming growth factor-beta1 (TGF beta1) and plasminogen activator inhibitor-1 (PAI-1) and its significance in premature infants with bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was performed on the clinical data of 96 very low birth weight infants (gestational age of <= 32 weeks) who survived for more than 28 days and were admitted to the Neonatal Intensive Care Unit between January 2010 and December 2012. These subjects were divided into BPD group (n=21) and non-BPD group (n=75). The expression of TGF-beta1 and PAI-1 in blood was measured by ELISA. RESULTS: The levels of TGF-beta1 and PAI-1 in the BPD group increased gradually from the 7th day to the 14th day and then to the 21st day after birth, and were significantly higher than in the non-BPD group at all time points (P<0.01). The TGF-beta1 and PAI-1 levels in the non-BPD group on the 7th, 14th, and 21st days after birth were not significantly different from each other (P>0.05). CONCLUSIONS: The expression of TGF-beta1 and PAI-1 in blood is elevated in premature infants with BPD, which may be associated with the development of BPD. PMID- 25140772 TI - [Efficacy of inhaled nitric oxide in premature infants with hypoxic respiratory failure]. AB - OBJECTIVE: To investigate the safety and efficacy of low-concentration inhaled nitric oxide (NO) in the treatment of hypoxic respiratory failure (HRF) among premature infants. METHODS: Sixty premature infants (gestational age <= 34 weeks) with HRF were randomized into NO and control groups between 2012 and 2013, with 30 cases in each group. Both groups received nasal continuous positive airway pressure (nCPAP) or mechanical ventilation. NO inhalation was continued for at least 7 days or until weaning in the NO group. The general conditions, blood gas results, complications, and clinical outcomes of the two groups were analyzed. RESULTS: The NO group showed significantly more improvement in blood gas results than the control group after 12 hours of treatment (P<0.05). After that, the change in oxygenation status over time showed no significant difference between the two groups (P>0.05). There were no significant differences in total time of assisted ventilation and duration of oxygen therapy between the two groups (P>0.05). The incidence of bronchopulmonary dysplasia (BPD), patent ductus arteriosus, necrotizing enterocolitis, retinopathy of prematurity, and pneumothorax in infants showed no significant differences between the NO and control groups (P>0.05), but the incidence of IVH and mortality were significantly lower in the NO group than in the control group (7% vs 17%, P<0.05; 3% vs 13%, P<0.05). CONCLUSIONS: NO inhalation may improve oxygenation status and reduce the mortality in premature infants with HRF, but it cannot reduce the incidence of BPD and the total time of mechanical ventilation or nCPAP and duration of oxygen therapy. NO therapy may have a brain-protective effect for premature infants with HRF and does not increase clinical complications. PMID- 25140774 TI - [Effects of enteral nutrition starting time on digestive function and growth rate in very low birth weight infants]. AB - OBJECTIVE: To study the appropriate time of starting enteral nutrition and observe the effects of different enteral nutrition starting times on the digestive function, growth rate, and nosocomial infection rate in very low birth weight infants (VLBWI). METHODS: All the VLBWI admitted to the neonatal intensive care unit between February and December, 2012 were selected. Depending on different times of starting enteral nutrition, these infants were divided into three groups: <= 3 days (n=116), 4-6 days (n=36), and >= 7 days (n=26). The effects of different enteral nutrition starting times on digestive function, growth rate and nosocomial infection rate were analyzed. RESULTS: The <= 3 days group had significantly higher milk intake than the other two groups at one week after birth; the <= 3 days and 4-6 days group had significantly higher milk intake than the >= 7 days group at two and three weeks after birth. The growth rate showed no significant differences between the three groups. The <= 3 days group had a significantly shorter time of central venous catheterization than the other two groups, and the >= 7 days group had a significantly longer time to full enteral feeding than the other two groups. The nosocomial infection rate of the <= 3 days group (13.8%) was significantly lower than that of the >= 7 days group (46.2%). CONCLUSIONS: For VLBWI, the time of starting enteral nutrition has no impact on growth rate, but starting enteral nutrition early can promote the development of gastrointestinal function, increase milk intake, shorten the time to full enteral feeding, reduce the time of central venous catheterization, and significantly reduce nosocomial infection rate. PMID- 25140775 TI - [A co-word analysis of current research on neonatal jaundice]. AB - OBJECTIVE: To investigate the research on neonatal jaundice in recent years by co word analysis and to summarize the hot spots and trend of research in this field in China. METHODS: The CNKI was searched with "neonate" and "jaundice" as the key words to identify the papers published from January 2009 to July 2013 that were in accordance with strict inclusion and exclusion criteria. To reveal the relationship between different high-frequency key words, Microsoft Office Excel 2013 was used for statistical analysis of key words, and Ucinet 6.0 and Netdraw were used for co-occurrence analysis. RESULTS: A total of 2 054 papers were included, and 44 high-frequency key words were extracted. The current hotspots of research on neonatal jaundice in China were displayed, and the relationship between different high-frequency key words was presented. CONCLUSIONS: There has been in-depth research on clinical manifestations and diagnosis of neonatal jaundice in China, but further research is needed to investigate the etiology, mechanism, and treatment of neonatal jaundice. PMID- 25140777 TI - [Efficacy of levetiracetam combined with short-term clonazepam in treatment of electrical status epilepticus during sleep in children with benign childhood epilepsy with centrotemporal spikes]. AB - OBJECTIVE: To study the efficacy of levetiracetam (LEV) combined with short-term clonazepam (CZP) in the treatment of electrical status epilepticus during sleep (ESES) in children with benign childhood epilepsy with centrotemporal spikes (BECCT). METHODS: Fifteen children (9 boys and 6 girls) diagnosed with BECCT with ESES, who had continuous spike-and-wave accounting for over 85% of the non-rapid eye movement sleep as monitored by 24-hours ambulatory EEG or 3-hours video EEG, were enrolled. The clinical manifestations and EEG characteristics of patients were retrospectively analyzed. These children received two months of CZP treatment in addition to oral LEV [20-40 mg/(kg.d)]. All patients were followed up for 6-18 months. RESULTS: The 15 children were orally given LEV in the early stage, but showed no improvement when reexamined by EEG or had seizures during treatment. Then, they received LEV in combination with short-term CZP. Re examinations at 1 and 6 months after treatment showed that 14 cases had significantly reduced discharge (only little discharge in the Rolandic area) or no discharge, as well as completely controlled seizure; one case had recurrent ESES and two epileptic seizures during follow-up. The recurrent case received the combination therapy again, and re-examinations 1 and 6 months later revealed normal EEG; no seizure occurred in the 8 months of follow-up. CONCLUSIONS: LEV combined with short-term CZP is effective and has few side effects in treating ESES syndrome among children with BECCT. PMID- 25140776 TI - [Clinical analysis of 10 cases of pediatric Crohn's disease]. AB - OBJECTIVE: To study the clinical features and treatment of pediatric Crohn's disease (CD). METHODS: Clinical data of 10 children with active CD diagnosed between 2005 and 2013 were retrospectively reviewed. RESULTS: Abdominal pain, diarrhea, and bloody stools were the most common symptoms in these patients, usually accompanied by different degrees of growth retardation and nutritional disorders. Fever was the main extraintestinal manifestation. Enteroscopy showed discontinuous and segmental mucosal hyperaemia and erosion, cobblestone appearance and mucosal ulceration. Abdominal ultrasound revealed uneven and segmental thickening of the intestinal wall. The pathological esamination showed many lymphocytes, eosinophils and plasma cells infiltrating into the lamina propria and partial atrophy of mucosal gland. C-reactive protein (CRP) level was significantly lower in the remission stage than in the acute stage and the recurrence stage (P<0.05). The erythrocyte sedimentation rate (ESR) was significantly lower in the remission stage than in the recurrence stage (P<0.05). Among mild cases identified by the pediatric Crohn's disease activity index (PCDAI) in the early stage of disease, the induced remission rate and maintained remission rate were 100% and 67%, respectively, with oral 5-aminosalicylic acid (5-ASA) and adrenocortical hormone. Among moderate and severe cases identified by the PCDAI, the partial remission rate was 100% with 5-ASA and adrenocortical hormone, but the maintained remission rate was not so good and the recurrence rate of disease was high. CONCLUSIONS: Pediatric CD has no specific clinical manifestations and laboratory test results. ESR and CRP can be used as the markers for evaluating the disease progression. 5-ASA has certain efficacy in inducing and maintaining remission of pediatric CD. There is a certain correlation between treatment outcome and the PCDAI score in the early stage of disease. PMID- 25140778 TI - [Clinical value of cranial MRI in the diagnosis and treatment of central nervous system candidiasis]. AB - OBJECTIVE: To study the clinical value of cranial magnetic resonance imaging (MRI) in the diagnosis and treatment of central nervous system candidiasis (CNSC), which has no specific clinical manifestations and has no rapid and specific diagnostic tools. METHODS: A retrospective analysis was performed on the clinical data of 10 children who were diagnosed with CNSC in Beijing Children's Hospital Affiliated to Capital Medical University between 2009 and 2013. RESULTS: Nine of the 10 children underwent cranial MRI within 8 days after admission, and 5 of the 9 children underwent contrast-enhanced MRI at the same time. Eight of the 9 children showed the features of meningoencephalitis, and 6 cases were accompanied by varying degrees of brain atrophy; one case showed hydrocephalus and cerebral abscess, and another case showed leukoencephalopathy. Six cases were found to have the features of cerebral vasculitis after infection in the first MRI after admission, including cerebral infarction (2 cases), venous sinus thrombosis (3 cases), and Moyamoya disease (1 case). Infectious granulomatous lesions were confirmed by contrast-enhanced MRI in 3 cases. Given the clinical manifestations, 8 of the 9 cases were diagnosed as suspected CNSC after MRI, and 7 of these cases received antifungal therapy before the pathogen test results were returned. The lesions on MRI were improved in 6 cases after 3-4 weeks of antifungal treatment. All the 10 children were diagnosed with CNSC by positive cerebrospinal fluid culture results. CONCLUSIONS: Cranial MRI, especially contrast-enhanced MRI, is of great significance for the diagnosis and treatment of CNSC. To confirm the guidance of MRI in the diagnosis and treatment of CNSC, further case-control studies are needed. PMID- 25140779 TI - [Association of folate metabolism genes MTRR and MTHFR with complex congenital abnormalities among Chinese population in Shanxi Province, China]. AB - OBJECTIVE: To explore the association of polymorphisms in folate metabolism genes, methionine synthase reductase (MTRR) gene and 5,10 methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital abnormalities and to further investigate its association with complex congenital abnormalities derived from three germ layers. METHODS: A total of 250 cases of birth defects (with complex congenital abnormalities including congenital heart disease, neural tube defects, and craniofacial anomalies) in Shanxi Province, China were included in the study. MTRR single nucleotide polymorphism (SNP) (rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and the genotyping results were compared with those of controls (n=420). RESULTS: SNPs rs1801394 and rs1801133 were associated with multiple birth defects. For the recessive model, individuals with GG genotype at rs1801394 and CC genotype at rs1801133 had a relatively low risk of developing birth defects, so the two genotypes were protective factors against birth defects. The homozygous recessive genotype at rs1801133, which served as a protective factor, was associated with ectoderm- or endoderm-derived complex congenital abnormalities, while the homozygous recessive genotype at rs1801394, which served as a protective factor, was associated with ectoderm-, mesoderm- or endoderm-derived complex congenital abnormalities. CONCLUSIONS: Among the Chinese population in Shanxi Province, the SNPs in folate metabolism genes (MTRR and MTHFR) are associated with complex congenital abnormalities and related to ectoderm, mesoderm or endoderm development. PMID- 25140780 TI - [Analysis of single nucleotide polymorphisms at IL-6-174 and TNF-beta NcoI in Chinese Han children in Guangzhou, China]. AB - OBJECTIVE: To investigate the single nucleotide polymorphisms (SNPs) at interleukin 6 (IL-6)-174 and TNF-beta NcoI in Chinese Han children in Guangzhou, China and to provide basic information for study on the association between IL-6 174 and TNF-beta NcoI polymorphisms and systemic inflammatory response syndrome (SIRS). METHODS: Allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism were used to determine the SNPs at IL-6-174 and TNF-beta NcoI in 481 children selected from the Han population in Guangzhou in 2012. Genotype analysis and comparison with other populations were made with reference to relevant literature. RESULTS: Chinese Han children in Guangzhou had only GG genotype at IL-6-174, and the SNP at this locus was rare or not seen in the Han population in Guangzhou. At TNF-beta NcoI, the frequencies of TNF-beta 1*1, TNF-beta 1*2, and TNF-beta 2*2 genotypes were 24.7%, 49.7%, and 25.6%, respectively. The sample distribution was in accordance with Hardy Weinberg equilibrium. The TNF-beta 1 allele frequency was significantly higher in Guangzhou Han population than in European and American white population (P<0.05). CONCLUSIONS: TNF-beta NcoI SNP is prevalent in the Han population in Guangzhou, and the distribution of alleles is significantly different from that in the white population. The sample from an Hardy-Weinberg equilibrium population can be further used for study on the association between TNF-beta NcoI SNP and SIRS in Chinese Han children in Guangzhou. IL-6-174 SNP is rare or not seen in the Han population in Guangzhou, so SNP at this locus cannot be selected for disease association analysis. PMID- 25140782 TI - [Clinical analysis of pediatric infectious atelectasis]. PMID- 25140781 TI - [Effect of UCP2-siRNA on inflammatory response of cardiomyocytes induced by septic serum]. AB - OBJECTIVE: To study the effect of uncoupling protein 2 (UCP2)-siRNA on the inflammatory response of rat cardiomyocytes (H9C2) induced by septic serum and to investigate the possible role of UCP2 in the development of septic cardiomyopathy. METHODS: Serum samples were separately collected from normal rats and septic rats. Cultured rat cardiac cells (H9C2) were randomly divided into blank control, normal serum, 10% septic serum, UCP2-siRNA+10% septic serum and negative siRNA+10% septic serum groups. Stimulation with 10% septic serum was performed for 12 hours in relevant groups. The mRNA expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) was measured by RT PCR. The expression of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-kappa B (NF-kappaB) was measured by Western blot. RESULTS: The expression levels of p-p38 and NF-kappaB in the UCP2-siRNA+10% septic serum group were significantly higher than in the 10% septic serum group (P<0.05). The UCP2-siRNA+10% septic serum group had a significantly higher TNF alpha mRNA expression than the 10% septic serum group (P<0.01), but IL-1beta mRNA expression showed no significant difference between the two groups. CONCLUSIONS: UCP2 plays a regulatory role in the activation of p38 MAPK and NF-kappaB and the expression of downstream inflammatory mediators in H9C2 cells stimulated with septic serum. PMID- 25140783 TI - [Effectiveness of external propranolol gel for treatment of superficial infantile hemangioma]. PMID- 25140784 TI - [A case report of Phelan-McDermid syndrome]. PMID- 25140785 TI - [Corpus callosum damage detected by MRI in a boy with herpes simplex encephalitis]. PMID- 25140786 TI - [Cutaneous myiasis in a young child]. PMID- 25140787 TI - [MonoMAC syndrome]. AB - MonoMAC syndrome is a newly discovered immune deficiency syndrome caused by GATA 2 mutation, which is an autosomal dominant genetic disease. MonoMAC syndrome has typical immune cell abnormalities, with severe infection and is prone to develop into a hematological disease. Therapeutics for this disease mainly relies on symptomatic treatment and hematopoietic stem cell transplantation. In this paper, the research advances in clinical manifestations, laboratory tests, pathogenesis, diagnosis and treatment of MonoMAC syndrome are reviewed. PMID- 25140788 TI - Removal of the iodinated X-ray contrast medium diatrizoate by anaerobic transformation. AB - The iodinated X-ray contrast medium diatrizoate is known to be very persistent in current wastewater treatment as well as in environmental compartments. In this study, the potential of anaerobic processes in soils, sediments, and during wastewater treatment to remove and transform diatrizoate was investigated. In anaerobic batch experiments with soil and sediment seven biologically formed transformation products (TPs) as well as the corresponding transformation pathway were identified. The TPs resulted from successive deiodinations and deacetylations. The final TP 3,5-diaminobenzoic acid (DABA) was stable under anaerobic conditions. However, DABA was further transformed under air atmosphere, indicating the potential for the mineralization of diatrizoate by combining anaerobic and aerobic conditions. With the development of a methodology using complementary liquid chromatography-electrospray ionization-tandem mass spectrometry and liquid chromatography-inductively coupled plasma-mass spectrometry techniques, all identified TPs were quantified and the mass balance could be closed without having authentic standards for four of the TPs available. The detection and quantification of diatrizoate TPs in groundwater, in technical wetlands with anaerobic zones, and in a pilot wastewater treatment plant established for anaerobic treatment highlights the transferability and up-scaling of the results attained by laboratory experiments to environmental conditions. PMID- 25140789 TI - Attitudes to aging in midlife are related to health conditions and mood. AB - BACKGROUND: Health is an important aspect of individuals' lives as they age. The aim of this study was to examine the relationship of sociodemographic factors, diagnosed chronic health conditions, and current depression with attitudes to aging in midlife. METHODS: A cross-sectional baseline analysis was conducted on the first 300 participants from the Canterbury Health, Ageing and Life Course study in New Zealand, a stratified randomized community longitudinal study of adults recruited between 49 and 51 years. Attitudes were measured using the Attitudes to Aging Questionnaire (AAQ) and analyzed with a range of prevalent diagnosed chronic conditions, current depression, and sociodemographic variables. RESULTS: Individuals perceived their physical aging more negatively after a diagnosis of hypertension, arthritis or asthma. Diagnosed lifetime depression and anxiety, and current depression, showed strong relationships with attitudes to aging across domains. After controlling for sociodemographic factors and current depression, individuals with diagnosed hypertension, arthritis, asthma, lifetime depression or anxiety continued to report significantly more negative attitudes to aging. Current depression showed the strongest associations with attitudes to aging and mediated relationships of health on attitudes to aging. CONCLUSIONS: Physical and mental health are related to attitudes to aging. Most chronic conditions examined are significantly associated with attitudes toward aging in the physical change domain. Diagnosed lifetime depression and anxiety, and current depression, are negatively related across attitudinal domains. Individuals can feel positive about aging while experiencing poorer health, but this is more difficult in the presence of low mood. PMID- 25140791 TI - Fungal siderophore metabolism with a focus on Aspergillus fumigatus. AB - Siderophores are chelators synthesized by microbes to sequester iron. This article summarizes the knowledge on the fungal siderophore metabolism with a focus on Aspergillus fumigatus. In recent years, A. fumigatus became a role model for fungal biosynthesis, uptake and degradation of siderophores as well as regulation of siderophore-mediated iron handling and the elucidation of siderophore functions. Siderophore functions comprise uptake, intracellular transport and storage of iron. This proved to be crucial not only for adaptation to iron starvation conditions but also for germination, asexual and sexual propagation, antioxidative defense, mutual interaction, microbial competition as well as virulence in plant and animal hosts. Recent studies also indicate the high potential of siderophores and its biosynthetic pathway to improve diagnosis and therapy of fungal infections. PMID- 25140792 TI - Are pharmaceuticals with evolutionary conserved molecular drug targets more potent to cause toxic effects in non-target organisms? AB - The ubiquitous use of pharmaceuticals has resulted in a continuous discharge into wastewater and pharmaceuticals and their metabolites are found in the environment. Due to their design towards specific drug targets, pharmaceuticals may be therapeutically active already at low environmental concentrations. Several human drug targets are evolutionary conserved in aquatic organisms, raising concerns about effects of these pharmaceuticals in non-target organisms. In this study, we hypothesized that the toxicity of a pharmaceutical towards a non-target invertebrate depends on the presence of the human drug target orthologs in this species. This was tested by assessing toxicity of pharmaceuticals with (miconazole and promethazine) and without (levonorgestrel) identified drug target orthologs in the cladoceran Daphnia magna. The toxicity was evaluated using general toxicity endpoints at individual (immobility, reproduction and development), biochemical (RNA and DNA content) and molecular (gene expression) levels. The results provide evidence for higher toxicity of miconazole and promethazine, i.e. the drugs with identified drug target orthologs. At the individual level, miconazole had the lowest effect concentrations for immobility and reproduction (0.3 and 0.022 mg L-1, respectively) followed by promethazine (1.6 and 0.18 mg L-1, respectively). At the biochemical level, individual RNA content was affected by miconazole and promethazine already at 0.0023 and 0.059 mg L-1, respectively. At the molecular level, gene expression for cuticle protein was significantly suppressed by exposure to both miconazole and promethazine; moreover, daphnids exposed to miconazole had significantly lower vitellogenin expression. Levonorgestrel did not have any effects on any endpoints in the concentrations tested. These results highlight the importance of considering drug target conservation in environmental risk assessments of pharmaceuticals. PMID- 25140794 TI - Souroubea sympetala (Marcgraviaceae): a medicinal plant that exerts anxiolysis through interaction with the GABAA benzodiazepine receptor. AB - The mode of action of the anxiolytic medicinal plant Souroubea sympetala was investigated to test the hypothesis that extracts and the active principle act at the pharmacologically important GABAA-benzodiazepine (GABAA-BZD) receptor. Leaf extracts prepared by ethyl acetate extraction or supercritical extraction, previously determined to have 5.54 mg/g and 6.78 mg/g of the active principle, betulinic acid, respectively, reduced behavioural parameters associated with anxiety in a rat model. When animals were pretreated with the GABAA-BZD receptor antagonist flumazenil, followed by the plant extracts, or a more soluble derivative of the active principle, the methyl ester of betulinic acid (MeBA), flumazenil eliminated the anxiety-reducing effect of plant extracts and MeBA, demonstrating that S. sympetala acts via an agonist action on the GABAA-BZD receptor. An in vitro GABAA-BZD competitive receptor binding assay also demonstrated that S. sympetala extracts have an affinity for the GABAA-BZD receptor, with an EC50 value of 123 MUg/mL (EtOAc leaf extract) and 154 MUg/mL (supercritical CO2 extract). These experiments indicate that S. sympetala acts at the GABAA-BZD receptor to elicit anxiolysis. PMID- 25140793 TI - Proteomics analysis of amyloid and nonamyloid prion disease phenotypes reveals both common and divergent mechanisms of neuropathogenesis. AB - Prion diseases are a heterogeneous group of neurodegenerative disorders affecting various mammals including humans. Prion diseases are characterized by a misfolding of the host-encoded prion protein (PrP(C)) into a pathological isoform termed PrP(Sc). In wild-type mice, PrP(C) is attached to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor and PrP(Sc) typically accumulates in diffuse nonamyloid deposits with gray matter spongiosis. By contrast, when mice lacking the GPI anchor are infected with the same prion inoculum, PrP(Sc) accumulates in dense perivascular amyloid plaques with little or no gray matter spongiosis. In order to evaluate whether different host biochemical pathways were implicated in these two phenotypically distinct prion disease models, we utilized a proteomics approach. In both models, infected mice displayed evidence of a neuroinflammatory response and complement activation. Proteins involved in cell death and calcium homeostasis were also identified in both phenotypes. However, mitochondrial pathways of apoptosis were implicated only in the nonamyloid form, whereas metal binding and synaptic vesicle transport were more disrupted in the amyloid phenotype. Thus, following infection with a single prion strain, PrP(C) anchoring to the plasma membrane correlated not only with the type of PrP(Sc) deposition but also with unique biochemical pathways associated with pathogenesis. PMID- 25140795 TI - Macular Changes Correlate with the Degree of Acute Anterior Uveitis in Patients with Spondyloarthropathy. AB - PURPOSE: To evaluate the correlation between anterior chamber inflammation and the central foveal thickness of the retina in a homogenous uveitic group (seronegative spondyloarthropathy (subgroup: ankylosing spondylitis)) of patients with the first acute anterior unilateral uveitic attack. METHODS: Central foveal thickness (FT) and perifoveal retinal thickness were recorded by optical coherence tomography (Optovue RTVue-100), and the difference between the two eyes was calculated. Statistical analysis was performed by Mathworks Matlab software. Anterior chamber inflammation was measured by laser flare photometry (Kowa FM 600). RESULTS: A statistically significant (p < .05) increase was found in retinal thickness in all OCT subfields in acute anterior uveitic eyes compared to healthy fellow eyes. There was a linear correlation between the degree of inflammation (laser flare photometry values) and central foveal thickness (r = .900, p < .001). CONCLUSIONS: We could demonstrate close correlation between macular thickness and inflammation in anterior uveitic patients with spondyloarthropathy. PMID- 25140796 TI - Functional roles of the dimer-interface residues in human ornithine decarboxylase. AB - Ornithine decarboxylase (ODC) catalyzes the decarboxylation of ornithine to putrescine and is the rate-limiting enzyme in the polyamine biosynthesis pathway. ODC is a dimeric enzyme, and the active sites of this enzyme reside at the dimer interface. Once the enzyme dissociates, the enzyme activity is lost. In this paper, we investigated the roles of amino acid residues at the dimer interface regarding the dimerization, protein stability and/or enzyme activity of ODC. A multiple sequence alignment of ODC and its homologous protein antizyme inhibitor revealed that 5 of 9 residues (residues 165, 277, 331, 332 and 389) are divergent, whereas 4 (134, 169, 294 and 322) are conserved. Analytical ultracentrifugation analysis suggested that some dimer-interface amino acid residues contribute to formation of the dimer of ODC and that this dimerization results from the cooperativity of these interface residues. The quaternary structure of the sextuple mutant Y331S/Y389D/R277S/D332E/V322D/D134A was changed to a monomer rather than a dimer, and the Kd value of the mutant was 52.8 uM, which is over 500-fold greater than that of the wild-type ODC (ODC_WT). In addition, most interface mutants showed low but detectable or negligible enzyme activity. Therefore, the protein stability of these interface mutants was measured by differential scanning calorimetry. These results indicate that these dimer-interface residues are important for dimer formation and, as a consequence, are critical for enzyme catalysis. PMID- 25140798 TI - A comparative study on in vitro osteogenic priming potential of electron spun scaffold PLLA/HA/Col, PLLA/HA, and PLLA/Col for tissue engineering application. AB - A comparative study on the in vitro osteogenic potential of electrospun poly-L lactide/hydroxyapatite/collagen (PLLA/HA/Col, PLLA/HA, and PLLA/Col) scaffolds was conducted. The morphology, chemical composition, and surface roughness of the fibrous scaffolds were examined. Furthermore, cell attachment, distribution, morphology, mineralization, extracellular matrix protein localization, and gene expression of human mesenchymal stromal cells (hMSCs) differentiated on the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA were also analyzed. The electrospun scaffolds with a diameter of 200-950 nm demonstrated well-formed interconnected fibrous network structure, which supported the growth of hMSCs. When compared with PLLA/H%A and PLLA/Col scaffolds, PLLA/Col/HA scaffolds presented a higher density of viable cells and significant upregulation of genes associated with osteogenic lineage, which were achieved without the use of specific medium or growth factors. These results were supported by the elevated levels of calcium, osteocalcin, and mineralization (P<0.05) observed at different time points (0, 7, 14, and 21 days). Furthermore, electron microscopic observations and fibronectin localization revealed that PLLA/Col/HA scaffolds exhibited superior osteoinductivity, when compared with PLLA/Col or PLLA/HA scaffolds. These findings indicated that the fibrous structure and synergistic action of Col and nano-HA with high-molecular-weight PLLA played a vital role in inducing osteogenic differentiation of hMSCs. The data obtained in this study demonstrated that the developed fibrous PLLA/Col/HA biocomposite scaffold may be supportive for stem cell based therapies for bone repair, when compared with the other two scaffolds. PMID- 25140799 TI - miR-203 suppresses the proliferation and migration and promotes the apoptosis of lung cancer cells by targeting SRC. AB - SRC, also known as proto-oncogene c-Src, is a non-receptor tyrosine kinase that plays an important role in cancer progression by promoting survival, angiogenesis, proliferation, and invasion pathways. In this study, we found that SRC protein levels were consistently upregulated in lung cancer tissues, but that SRC mRNA levels varied randomly, suggesting that a post-transcriptional mechanism was involved in SRC regulation. Because microRNAs (miRNAs) are powerful post transcriptional regulators of gene expression, we used bioinformatic analyses to search for miRNAs that potentially target SRC. We identified specific targeting sites for miR-203 in the 3'-untranslated region (3'-UTR) of SRC. We then experimentally validated miR-203 as a direct regulator of SRC using cell transfection and luciferase assays and showed that miR-203 inhibited SRC expression and consequently triggered suppression of the SRC/Ras/ERK pathway. Finally, we demonstrated that the repression of SRC by miR-203 suppressed the proliferation and migration and promoted the apoptosis of lung cancer cells. In summary, this study provides the first clues regarding the role of miR-203 as a tumor suppressor in lung cancer cells through the inhibition of SRC translation. PMID- 25140800 TI - Photodynamic therapy using systemic administration of 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode for methicillin-resistant Staphylococcus aureus-infected ulcers in mice. AB - Bacterial resistance to antibiotics has become a worldwide problem. One potential alternative for bacterial control is photodynamic therapy. 5-aminolevulinic acid is a natural precursor of the photosensitizer protoporphyrin IX. Relatively little is known about the antibacterial efficacy of photodynamic therapy using the systemic administration of 5-aminolevulinic acid; a few reports have shown that 5-aminolevulinic acid exerts photodynamic effects on methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In this study, we evaluated the effectiveness of photodynamic therapy using 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode in vitro and in vivo for the treatment of MRSA. We found that 5-aminolevulinic acid photodynamic therapy with the light-emitting diode had an in-vitro bactericidal effect on MRSA. In vivo, protoporphyrin IX successfully accumulated in MRSA on ulcer surfaces after intraperitoneal administration of 5-aminolevulinic acid to mice. Furthermore, 5-aminolevulinic acid photodynamic therapy accelerated wound healing and decreased bacterial counts on ulcer surfaces; in contrast, vancomycin treatment did not accelerate wound healing. Our findings indicate that 5-aminolevulinic acid photodynamic therapy may be a new treatment option for MRSA-infected wounds. PMID- 25140801 TI - Retention of habitat complexity minimizes disassembly of reef fish communities following disturbance: a large-scale natural experiment. AB - High biodiversity ecosystems are commonly associated with complex habitats. Coral reefs are highly diverse ecosystems, but are under increasing pressure from numerous stressors, many of which reduce live coral cover and habitat complexity with concomitant effects on other organisms such as reef fishes. While previous studies have highlighted the importance of habitat complexity in structuring reef fish communities, they employed gradient or meta-analyses which lacked a controlled experimental design over broad spatial scales to explicitly separate the influence of live coral cover from overall habitat complexity. Here a natural experiment using a long term (20 year), spatially extensive (~ 115,000 kms(2)) dataset from the Great Barrier Reef revealed the fundamental importance of overall habitat complexity for reef fishes. Reductions of both live coral cover and habitat complexity had substantial impacts on fish communities compared to relatively minor impacts after major reductions in coral cover but not habitat complexity. Where habitat complexity was substantially reduced, species abundances broadly declined and a far greater number of fish species were locally extirpated, including economically important fishes. This resulted in decreased species richness and a loss of diversity within functional groups. Our results suggest that the retention of habitat complexity following disturbances can ameliorate the impacts of coral declines on reef fishes, so preserving their capacity to perform important functional roles essential to reef resilience. These results add to a growing body of evidence about the importance of habitat complexity for reef fishes, and represent the first large-scale examination of this question on the Great Barrier Reef. PMID- 25140802 TI - Reducing Igf-1r levels leads to paradoxical and sexually dimorphic effects in HD mice. AB - Many of the neurodegenerative diseases that afflict people in later life are associated with the formation of protein aggregates. These so-called "proteinopathies" include Alzheimer's disease (AD) and Huntington's disease (HD). The insulin/insulin-like growth factor signalling (IIS) pathway has been proposed to modulate such diseases in model organisms, as well as the general ageing process. In this pathway, insulin-like growth factor binds to insulin-like growth factor receptors, such as the insulin-like growth factor 1 receptor (IGF-1R). Heterozygous deletion of Igf-1r has been shown to lead to increased lifespan in mice. Reducing the activity of this pathway had benefits in a HD C. elegans model, and some of these may be attributed to the expected inhibition of mTOR activity resulting in an increase in autophagy, which would enhance mutant huntingtin clearance. Thus, we tested if heterozygous deletion of Igf-1r would lead to benefits in HD related phenotypes in the mouse. Surprisingly, reducing Igf-1r levels led to some beneficial effects in HD females, but also led to some detrimental effects in HD males. Interestingly, Igf-1r deficiency had no discernible effects on downstream mTOR signalling in HD mice. These results do not support a broad beneficial effect of diminishing the IIS pathway in HD pathology in a mammalian system. PMID- 25140805 TI - High-throughput screening system to identify small molecules that induce internalization and degradation of HER2. AB - Overexpression of growth factor receptors in cancers, e.g., human epidermal growth factor receptor 2 (HER2) in ovarian and breast cancers, is associated with aggressiveness. A possible strategy to treat cancers that overexpress those receptors is blockade of receptor signaling by inducing receptor internalization and degradation. In this study, we developed a cell-based high-throughput screening (HTS) system to identify small molecules that induce HER2 internalization by employing our recently developed acidic-pH-activatable probe in combination with protein labeling technology. Our HTS system enabled facile and reliable quantification of HER2 internalization with a Z' factor of 0.66 and a signal-to-noise ratio of 44.6. As proof of concept, we used the system to screen a ~155,000 small-molecule library and identified three hits that induced HER2 internalization and degradation via at least two distinct mechanisms. This HTS platform should be adaptable to other disease-related receptors in addition to HER2. PMID- 25140804 TI - In vivo efficacy of a synthetic coumarin derivative in a murine model of aspergillosis. AB - Despite advances in therapeutic modalities, aspergillosis remains a leading cause of mortality. This has necessitated the identification of effective and safe antifungal molecules. In the present study, in vivo safety and antifungal efficacy of a coumarin derivative, N, N, N-Triethyl-11-(4-methyl-2-oxo-2H benzopyran-7-yloxy)-11-oxoundecan-1-aminium bromide (SCD-1), was investigated. The maximum tolerable dose of compound was determined according to OECD 423 guidelines. The compound could be assigned to category IV of the Globally Harmonized System and its LD50 cut-off was found to be 2000 mg/kg body weight. The survival increased in Aspergillus fumigatus-infected mice treated with a dose of 200 mg/kg, orally or 100 mg/kg body weight, intraperitoneally, of SCD-1 in comparison to infected-untreated animals. The SCD-1 treatment resulted in significant reduction in colony counts in vital organs of the animals. Its protective effect was also observed on day 14 as there was marked reduction in fungal colonies. The treatment with SCD-1 also reduced the levels of serum biochemical parameters with respect to infected-untreated animals. It could be concluded that SCD-1 is a quite safe antifungal compound, which conferred dose dependent protection against experimental aspergillosis. Therefore, SCD-1 holds potential for developing new formulations for aspergillosis. PMID- 25140803 TI - Cellular membrane accommodation to thermal oscillations in the coral Seriatopora caliendrum. AB - In the present study, the membrane lipid composition of corals from a region with tidally induced upwelling was investigated. The coral community is subject to strong temperature oscillations yet flourishes as a result of adaptation. Glycerophosphocholine profiling of the dominant pocilloporid coral, Seriatopora caliendrum, was performed using a validated method. The coral inhabiting the upwelling region shows a definite shift in the ratio of lipid molecular species, covering several subclasses. Mainly, the coral possesses a higher percentage of saturated, monounsaturated and polyunsaturated plasmanylcholines and a lower percentage of polyunsaturated phosphatidylcholines. Higher levels of lyso plasmanylcholines containing saturated or monounsaturated fatty acid chains were also revealed in coral tissue at the distal portion of the branch. Based on the physicochemical properties of these lipids, we proposed mechanisms for handling cellular membrane perturbations, such as tension, induced by thermal oscillation to determine how coral cells are able to spontaneously maintain their physiological functions, in both molecular and physical terms. Interestingly, the biochemical and biophysical properties of these lipids also have beneficial effects on the resistance, maintenance, and growth of the corals. The results of this study suggest that lipid metabolic adjustment is a major factor in the adaption of S. caliendrum in upwelling regions. PMID- 25140806 TI - The perioperative management of patients undergoing combined heart-liver transplantation. AB - BACKGROUND: Combined heart-liver transplantation (CHLT) is an uncommonly performed procedure for patients with coexisting cardiac and liver disease. METHODS: A retrospective review was performed of patients undergoing CHLT at our institution from 1999 to 2013. Information related to preoperative organ function, intraoperative management, surgical approach, transfusions, postoperative findings, and 30-day mortality was reviewed. RESULTS: Twenty-seven CHLT were performed, with 4 of the 27 including simultaneous kidney transplantation. Familial amyloidosis was the indication for 21 CHLTs (78%), and 12 of these explanted livers were used for domino transplantations. Nineteen patients (70%) were receiving inotropic infusions at the time of organ availability. Median preoperative model for end-stage liver disease score was 12. Liver transplantation immediately preceded cardiac transplantation in 2 of the 27 cases because of the presence of high titer donor-specific antibodies and the potential of the liver to lead to a reduction in the antibody titer. Venovenous bypass was used in 14 operations (52%) which were performed with the caval interposition approach to liver transplantation, cardiopulmonary bypass during liver transplantation in two cases (7%), and no bypass in 11 operations (41%) performed with caval sparing (piggyback) surgical technique. Postoperatively, median duration of mechanical ventilation, intensive care unit stay, and hospital stay until discharge were 1 day, 5.5 days, and 15 days, respectively. Transfusions in the first 48 hr after CHLT were not substantial in most patients. One patient died within 30 days of CHLT. CONCLUSION: Combined heart-liver transplantation is a life-saving operation that is performed with relatively low mortality and can be successfully performed in select patients with congenital or acquired cardiac disease. PMID- 25140807 TI - Diet and human mobility from the lapita to the early historic period on Uripiv island, Northeast Malakula, Vanuatu. AB - Vanuatu was first settled ca. 3000 years ago by populations associated with the Lapita culture. Models of diet, subsistence practices, and human interaction for the Lapita and subsequent occupation periods have been developed mainly using the available archaeological and paleoenvironmental data. We test these models using stable (carbon, nitrogen, and sulfur) and radiogenic (strontium) isotopes to assess the diet and childhood residency of past communities that lived on the small (<1 km2) island of Uripiv, located off the northeast coast of Malakula, Vanuatu. The burials are from the initial Lapita occupation of the island (ca. 2800-2600 BP), the subsequent later Lapita (LL, ca. 2600-2500 BP) and post-Lapita (PL, ca. 2500-2000 BP) occupations, in addition to a late prehistoric/historic (LPH, ca. 300-150 BP) occupation period. The human stable isotope results indicate a progressively more terrestrial diet over time, which supports the archaeological model of an intensification of horticultural and arboricultural systems as local resources were depleted, populations grew, and cultural situations changed. Pig diets were similar and included marine foods during the Lapita and PL periods but were highly terrestrial during the LPH period. This dietary pattern indicates that there was little variation in animal husbandry methods during the first 800 years of prehistory; however, there was a subsequent change as animal diets became more controlled in the LPH period. After comparison with the local bioavailable 87Sr/86Sr baseline, all of the Lapita and LPH individuals appeared to be 'local', but three of the PL individuals were identified as "non-local." We suggest that these "non-locals" moved to the island after infancy or childhood from one of the larger islands, supporting the model of a high level of regional interaction during the post-Lapita period. PMID- 25140809 TI - Urbanisation at multiple scales is associated with larger size and higher fecundity of an orb-weaving spider. AB - Urbanisation modifies landscapes at multiple scales, impacting the local climate and changing the extent and quality of natural habitats. These habitat modifications significantly alter species distributions and can result in increased abundance of select species which are able to exploit novel ecosystems. We examined the effect of urbanisation at local and landscape scales on the body size, lipid reserves and ovary weight of Nephila plumipes, an orb weaving spider commonly found in both urban and natural landscapes. Habitat variables at landscape, local and microhabitat scales were integrated to create a series of indexes that quantified the degree of urbanisation at each site. Spider size was negatively associated with vegetation cover at a landscape scale, and positively associated with hard surfaces and anthropogenic disturbance on a local and microhabitat scale. Ovary weight increased in higher socioeconomic areas and was positively associated with hard surfaces and leaf litter at a local scale. The larger size and increased reproductive capacity of N.plumipes in urban areas show that some species benefit from the habitat changes associated with urbanisation. Our results also highlight the importance of incorporating environmental variables from multiple scales when quantifying species responses to landscape modification. PMID- 25140810 TI - Synthesis of the erythrina alkaloid erysotramidine. AB - A concise synthesis of erysotramidine (an alkaloid belonging to the erythrina family) was achieved starting with an inexpensive phenol and amine derivative. The synthesis is based on oxidative phenol dearomatizations mediated by a hypervalent iodine reagent and includes a novel route to a key indolinone moiety. PMID- 25140811 TI - Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain. AB - O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2 +/- 2 vs 7.9 +/- 1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4 +/- 2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3 +/- 2 vs 7.5 +/- 2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1 +/- 2 vs 7.4 +/- 2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca(2+)/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction. PMID- 25140813 TI - Effects of bromopride on expression of metalloproteinases and interleukins in left colonic anastomoses: an experimental study. AB - Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1alpha, MMP-8, MMP-13, IL-beta, IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). On the third POD, bromopride was associated with increased MMP-1alpha, MMP-13, IL-6, IFN-gamma, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-gamma gene expression and decreased MMP-1, TNF-alpha, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-alpha. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process. PMID- 25140812 TI - Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle. AB - The aim of the present study was to determine the mechanisms underlying the relaxant effect of adrenomedullin (AM) in rat cavernosal smooth muscle (CSM) and the expression of AM system components in this tissue. Functional assays using standard muscle bath procedures were performed in CSM isolated from male Wistar rats. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR), and Subtypes 1, 2 and 3 of the receptor activity-modifying protein (RAMP) family were assessed by Western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Nitrate and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha); a stable product of prostacyclin) levels were determined using commercially available kits. Protein and mRNA of AM, CRLR, and RAMP 1, -2, and -3 were detected in rat CSM. Immunohistochemical assays demonstrated that AM and CRLR were expressed in rat CSM. AM relaxed CSM strips in a concentration-dependent manner. AM(22-52), a selective antagonist for AM receptors, reduced the relaxation induced by AM. Conversely, CGRP(8-37), a selective antagonist for calcitonin gene-related peptide receptors, did not affect AM-induced relaxation. Preincubation of CSM strips with N(G)-nitro-L arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor), 1H (1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, quanylyl cyclase inhibitor), Rp-8 Br-PET-cGMPS (cGMP-dependent protein kinase inhibitor), SC560 [5-(4-chlorophenyl) 1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole, selective cyclooxygenase-1 inhibitor], and 4-aminopyridine (voltage-dependent K(+) channel blocker) reduced AM-induced relaxation. On the other hand, 7-nitroindazole (selective neuronal nitric oxide synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), H89 (protein kinase A inhibitor), SQ22536 [9-(tetrahydro-2-furanyl) 9H-purin-6-amine, adenylate cyclase inhibitor], glibenclamide (selective blocker of ATP-sensitive K(+) channels), and apamin (Ca(2+)-activated channel blocker) did not affect AM-induced relaxation. AM increased nitrate levels and 6-keto PGF1alpha in rat CSM. The major new contribution of this research is that it demonstrated expression of AM and its receptor in rat CSM. Moreover, we provided evidence that AM-induced relaxation in this tissue is mediated by AM receptors by a mechanism that involves the nitric oxide-cGMP pathway, a vasodilator prostanoid, and the opening of voltage-dependent K(+) channels. PMID- 25140814 TI - Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy. AB - The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children. PMID- 25140815 TI - Effects of immobilization and remobilization on the ankle joint in Wistar rats. AB - A sprained ankle is a common musculoskeletal sports injury and it is often treated by immobilization of the joint. Despite the beneficial effects of this therapeutic measure, the high prevalence of residual symptoms affects the quality of life, and remobilization of the joint can reverse this situation. The aim of this study was to analyze the effects of immobilization and remobilization on the ankle joint of Wistar rats. Eighteen male rats had their right hindlimb immobilized for 15 days, and were divided into the following groups: G1, immobilized; G2, remobilized freely for 14 days; and G3, remobilized by swimming and jumping in water for 14 days, performed on alternate days, with progression of time and a series of exercises. The contralateral limb was the control. After the experimental period, the ankle joints were processed for microscopic analysis. Histomorphometry did not show any significant differences between the control and immobilized/remobilized groups and members, in terms of number of chondrocytes and thickness of the articular cartilage of the tibia and talus. Morphological analysis of animals from G1 showed significant degenerative lesions in the talus, such as exposure of the subchondral bone, flocculation, and cracks between the anterior and mid-regions of the articular cartilage and the synovial membrane. Remobilization by therapeutic exercise in water led to recovery in the articular cartilage and synovial membrane of the ankle joint when compared with free remobilization, and it was shown to be an effective therapeutic measure in the recovery of the ankle joint. PMID- 25140816 TI - A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model. AB - We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use. PMID- 25140817 TI - Dynamic expression of desmin, alpha-SMA and TGF-beta1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats. AB - We previously described a selective bile duct ligation model to elucidate the process of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary stenosis. Using this model, we identified changes in the expression of alpha smooth muscle actin (alpha-SMA) both in the obstructed parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin and TGF-beta1, molecules known to be involved in hepatic fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of liver fibrosis in this experimental model are not fully understood. This study aimed to evaluate the molecular changes in an experimental model of selective bile duct ligation and to compare the gene expression changes observed in RT-PCR and in real-time quantitative PCR (qRT-PCR). Twenty-eight Wistar rats of both sexes and weaning age (21-23 days old) were used. The rats were separated into groups that were assessed 7 or 60 days after selective biliary duct ligation. The expression of desmin, alpha-SMA and TGF-beta1 was examined in tissue from hepatic parenchyma with biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO), using RT-PCR and qRT-PCR. The results obtained in this study using these two methods were significantly different. The BO parenchyma had a more severe fibrogenic reaction, with increased alpha-SMA and TGF-beta1 expression after 7 days. The WBO parenchyma presented a later, fibrotic response, with increased desmin expression 7 days after surgery and increased alpha-SMA 60 days after surgery. The qRT-PCR technique was more sensitive to expression changes than the semiquantitative method. PMID- 25140820 TI - Phosphine complexes of aluminium(III) halides - preparation and structural and spectroscopic systematics. AB - Six-coordinate pseudo-octahedral complexes trans-[AlX2(L-L)2][AlX4] (X = Cl, Br or I; L-L = o-C6H4(PMe2)2, Me2P(CH2)2PMe2) are produced from reaction of AlX3 with the diphosphine in CH2Cl2 (X = Cl) or toluene (X = Br or I) solution. Four coordinate dimers [Cl3Al(MU-L'-L')AlCl3] (L'-L' = Me2P(CH2)2PMe2, Cy2P(CH2)2PCy2), and the tetrahedral cation [AlCl2{o-C6H4(PPh2)2}][AlCl4] were also obtained. Both four- and five-coordinate complexes [AlX3(PMe3)] and [AlX3(PMe3)2] could be isolated with PMe3 depending upon the ratio of reagents used. These extremely moisture sensitive complexes have been characterised by microanalysis, IR and multinuclear NMR ((1)H, (31)P{(1)H} and (27)Al) spectroscopy. X-ray crystal structures are reported for [AlCl2{o C6H4(PMe2)2}2][AlCl4], [AlCl2{Me2P(CH2)2PMe2}2][AlCl4], [Cl3Al{MU Me2P(CH2)2PMe2}AlCl3], [Cl3Al{MU-Cy2P(CH2)2PCy2}AlCl3], [AlCl3(PMe3)], [AlCl3(PMe3)2], and for the six-coordinate cation complex [AlCl2{o C6H4(PPh2)2}2][AlCl4], although a bulk sample of the last could not be isolated. Tertiary arsines (AsPh3 or AsEt3) form only 1 : 1 complexes even with excess arsine present. The unstable [AlCl2{o-C6H4(AsMe2)2}][AlCl4] is also described, and shown to decompose rapidly in CH2Cl2 solution to form the diquaternised diarsine cation [o-C6H4(AsMe2)2(CH2)][AlCl4]2, which was fully characterised. Comparisons are drawn with the corresponding gallium(iii) systems (Cheng et al., Inorg. Chem., 2007, 46, 7215-7223) and with AlX3 complexes of Group 16 ligands (George et al., Dalton Trans., 2014, 43, 3637-3648), and it is concluded that the differences between the Al and Ga systems reflect the higher Lewis acidity of aluminium(iii) towards soft donor ligands. PMID- 25140819 TI - A continuous-flow C. elegans sorting system with integrated optical fiber detection and laminar flow switching. AB - We present a high-throughput continuous-flow C. elegans sorting device that works based on integrated optical fiber detection and laminar flow switching. Two types of genetically engineered nematodes are allowed to flow into the device and their genotypes are detected based on their fluorescence, without the need for immobilization, by integrated optical fibers. A novel dynamic fluidic switch sorts the nematodes to desired outlets. By changing input pressures of the control inlets, the laminar flow path is altered to steer the nematodes to appropriate outlets. Compared to previously reported microfluidic C. elegans sorting devices, sorting in this system is conducted in a continuous flow environment without any immobilization technique or need for multilayer mechanical valves to open and close the outlets. The continuous flow sorter not only increases the throughput but also avoids any kind of invasive or possibly damaging mechanical or chemical stimulus. We have characterized both the detection and the switching accuracy of the sorting device at different flow rates, and efficiencies approaching 100% can be achieved with a high throughput of about one nematode per second. To confirm that there was no significant damage to C. elegans following sorting, we recovered the sorted worms, finding no deaths and no differences in behavior and propagation compared to control. PMID- 25140818 TI - Synthesis of isocoumarins with different substituted patterns via Passerini-aldol sequence. AB - An efficient combination between the Passerini three-component reaction and aldol condensation has been developed for the synthesis of bicyclic isocoumarins with different substituted patterns via solvent-dependent domino pathways. These two operationally friendly methods simultaneously install C-O and C-C bonds in a one pot manner, allowing the utilization of low-cost and readily accessible 2 formylbenzoic acid, isocyanides, and arylglyoxals. Mechanisms of formation of different substituted isocoumarin derivatives are also proposed. PMID- 25140821 TI - Function and evolution of two forms of SecDF homologs in Streptomyces coelicolor. AB - The general secretion (Sec) pathway plays a prominent role in bacterial protein export, and the accessory component SecDF has been shown to improve transportation efficiency. Inspection of Streptomyces coelicolor genome reveals the unexpected presence of two different forms of secDF homologous genes: one in fused form (secDF) and the other in separated form (secD and secF). However, the functional role of two SecDF homologs in S. coelicolor has not yet been determined. Transcriptional analysis of secDF homologs reveals that these genes are constitutively expressed. However, the transcript levels of secD and secF are much higher than that of secDF in S. coelicolor. Deletion of secDF or/and secD/secF in S. coelicolor did result in reduced secretion efficiency of Xylanase A and Amylase C, suggesting that they may have redundant functions for Sec dependent translocation pathway. Moreover, our results also indicate that SecD/SecF plays a more prominent role than SecDF in protein translocation. Evolutionary analysis suggests that the fused and separated SecDF homologs in Streptomyces may have disparate evolutionary ancestries. SecD/SecF may be originated from vertical transmission of existing components from ancestor of Streptomyces species. However, SecDF may be derived from bacterial ancestors through horizontal gene transfer. Alternately, it is also plausible that SecDF may have arisen through additional gene duplication and fusion events. The acquisition of a second copy may confer a selective benefit to Streptomyces by enhancing protein transport capacity. Taken together, our results provide new insights into the potential biological function and evolutionary aspects of the prokaryotic SecDF complex. PMID- 25140822 TI - Nonlinear pedagogy: an effective approach to cater for individual differences in learning a sports skill. AB - Learning a sports skill is a complex process in which practitioners are challenged to cater for individual differences. The main purpose of this study was to explore the effectiveness of a Nonlinear Pedagogy approach for learning a sports skill. Twenty-four 10-year-old females participated in a 4-week intervention involving either a Nonlinear Pedagogy (i.e.,manipulation of task constraints including equipment and rules) or a Linear Pedagogy (i.e., prescriptive, repetitive drills) approach to learn a tennis forehand stroke. Performance accuracy scores, movement criterion scores and kinematic data were measured during pre-intervention, post-intervention and retention tests. While both groups showed improvements in performance accuracy scores over time, the Nonlinear Pedagogy group displayed a greater number of movement clusters at post test indicating the presence of degeneracy (i.e., many ways to achieve the same outcome). The results suggest that degeneracy is effective for learning a sports skill facilitated by a Nonlinear Pedagogy approach. These findings challenge the common misconception that there must be only one ideal movement solution for a task and thus have implications for coaches and educators when designing instructions for skill acquisition. PMID- 25140824 TI - Seeking small molecules for singlet fission: a heteroatom substitution strategy. AB - We design theoretically small molecule candidates for singlet fission chromophores, aiming to achieve a balance between sufficient diradical character and kinetic persistence. We develop a perturbation strategy based on the captodative effect to introduce diradical character into small pi-systems. Specifically, this can be accomplished by replacing pairs of not necessarily adjacent C atoms with isoelectronic and isosteric pairs of B and N atoms. Three rules of thumb emerge from our studies to aid further design: (i) Lewis structures provide insight into likely diradical character; (ii) formal radical centers of the diradical must be well-separated; (iii) stabilization of radical centers by a donor (N) and an acceptor (B) is essential. Following the rules, we propose candidate molecules. Employing reliable multireference calculations for excited states, we identify three likely candidate molecules for SF chromophores. These include a benzene, a napthalene, and an azulene, where four C atoms are replaced by a pair of B and a pair of N atoms. PMID- 25140823 TI - HLA-B27 and human beta2-microglobulin affect the gut microbiota of transgenic rats. AB - The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by the presence of the HLA-B27 gene. We identified differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and human beta2-microglobulin (hbeta2m), compared with wild-type Lewis rats, using biome representational in situ karyotyping (BRISK) and 16S rRNA gene sequencing. 16S sequencing revealed significant differences between transgenic animals and wild type animals by principal coordinates analysis. Further analysis of the data set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae relative abundance in the transgenic animals compared to the wild type animals. By BRISK analysis, species-specific differences included an increase in Bacteroides vulgatus abundance in HLA-B27/hbeta2m and hbeta2m compared to wild type rats. The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene. PMID- 25140827 TI - The influence of a Te-depleted surface on the thermoelectric transport properties of Bi2Te3 nanowires. AB - We report on thermoelectric transport measurements along the basal plane of several individual, single-crystalline Bi2Te3 nanowires (NWs) with different cross-sectional areas, grown by a vapor-liquid-solid method. Lithographically defined microdevices allowed us to determine the Seebeck coefficient S, electrical conductivity sigma, and thermal conductivity kappa of individual NWs. The NWs studied show near intrinsic transport properties with low electrical conductivities of around sigma = (3.2 +/- 0.9) * 104 Omega-1 m-1 at room temperature. We observe a transition of the Seebeck coefficient from positive to negative values (S = +133 MUVK-1 to S = -87 MUVK-1) with increasing surface-to volume ratio at room temperature, which can be explained by the presence of an approximately 5 nm thick Te-depleted layer at the surface of the NWs. The thermal conductivities of our NWs are in the range of kappa = (1.4 +/- 0.4) Wm-1 K-1 at room temperature, which is lower than literature values for bulk Bi2Te3. We attribute this suppression in thermal conductivity to enhanced scattering of phonons at the surface of the NWs. Despite their reduced thermal conductivities, the NWs investigated only show a moderate figure of merit between 0.02 and 0.18 due to their near intrinsic transport properties. PMID- 25140825 TI - Targeted capture and heterologous expression of the Pseudoalteromonas alterochromide gene cluster in Escherichia coli represents a promising natural product exploratory platform. AB - Marine pseudoalteromonads represent a very promising source of biologically important natural product molecules. To access and exploit the full chemical capacity of these cosmopolitan Gram-(-) bacteria, we sought to apply universal synthetic biology tools to capture, refactor, and express biosynthetic gene clusters for the production of complex organic compounds in reliable host organisms. Here, we report a platform for the capture of proteobacterial gene clusters using a transformation-associated recombination (TAR) strategy coupled with direct pathway manipulation and expression in Escherichia coli. The ~34 kb pathway for production of alterochromide lipopeptides by Pseudoalteromonas piscicida JCM 20779 was captured and heterologously expressed in E. coli utilizing native and E. coli-based T7 promoter sequences. Our approach enabled both facile production of the alterochromides and in vivo interrogation of gene function associated with alterochromide's unusual brominated lipid side chain. This platform represents a simple but effective strategy for the discovery and biosynthetic characterization of natural products from marine proteobacteria. PMID- 25140828 TI - Structure, phase transition, and controllable thermal expansion behaviors of Sc(2 x)Fe(x)Mo3O12. AB - The crystal structures, phase transition, and thermal expansion behaviors of solid solutions of Sc(2-x)Fe(x)Mo3O12 (0 <= x <= 2) have been examined using X ray diffraction (XRD), neutron powder diffraction (NPD), and differential scanning calorimetry (DSC). At room temperature, samples crystallize in a single orthorhombic structure for the compositions of x < 0.6 and monoclinic for x >= 0.6, respectively. DSC results indicate that the phase transition temperature from monoclinic to orthorhombic structure is enhanced by increasing the Fe(3+) content. High-temperature XRD and NPD results show that Sc(1.3)Fe(0.7)Mo3O12 exhibits near zero thermal expansion, and the volumetric coefficients of thermal expansion derived from XRD and NPD are 0.28 * 10(-6) degrees C(-1) (250-800 degrees C) and 0.65 * 10(-6) degrees C(-1) (227-427 degrees C), respectively. NPD results of Sc2Mo3O12 (x = 0) and Sc(1.3)Fe(0.7)Mo3O12 (x = 0.7) indicate that Fe substitution for Sc induces reduction of the mean Sc(Fe)-Mo nonbond distance and the different thermal variations of Sc(Fe)-O5-Mo2 and Sc(Fe)-O3-Mo2 bond angles. The correlation between the displacements of oxygen atoms and the variation of unit cell parameters was investigated in detail for Sc2Mo3O12. PMID- 25140830 TI - Symptomatic spinal leptomeningeal metastasis from intracranial glioblastoma multiforme. PMID- 25140831 TI - Destabilization effect of transition metal fluorides on sodium borohydride. AB - The effect of transition metal fluorides on the decomposition of NaBH4 has been investigated for NaBH4 ball milled with TiF3, MnF3 or FeF3. The compounds were examined by thermal programmed desorption with residual gas analysis, thermo gravimetric analysis and volumetric measurements using a Sieverts-type apparatus. The phase formation process during thermal decomposition was studied by in situ synchrotron radiation powder X-ray diffraction on the as-milled powders. NaBF4 was among the products in all mechano-chemical reactions. (11)B-NMR spectra analysis gave NaBF4 : NaBH4 ratios of 1 : 150 for Na-Ti, 1 : 40 for Na-Mn, and 1 : 10 for Na-Fe. Pure NaBH4 possessed a hydrogen release onset temperature of 430 degrees C. The hydrogen release in the NaBH4-MnF3 system began as low as 130 degrees C. FeF3 decreased the onset temperature to 161 degrees C and TiF3 to 200 degrees C. TiF3 reacted completely with NaBH4 below 320 degrees C. All the examined systems have negligible emissions of diborane species. H-sorption studies performed at selected temperatures above 300 degrees C exhibited relatively fast desorption kinetics. Partial hydrogen re-absorption was observed for the Na-Mn and Na-Fe samples. PMID- 25140832 TI - Silver-catalysed direct amination of unactivated C-H bonds of functionalized molecules. AB - Carbon-nitrogen bond formation from inert C-H bonds is an ideal organic transformation and a highly desirable method for the synthesis of N-containing molecules due to its high efficiency and atom economy. In this report, we develop a general reaction to achieve an unprecedented selective intramolecular amination of unactivated C-H bond in the absence of complex directing groups. Functionalized heterocyclic products are built up from readily available linear amines through simple and reliable silver catalysis, representing a new silver based C-H functionalization. This method displays preference for primary sp(3) C H bonds and exhibits distinct chemo- and regioselectivity compared to existing methods of direct amination (Hofmann-Loffler-Freytag reaction and nitrene insertion). The study highlights the manipulation of unfunctionalized groups in organic molecules to furnish complex structural units in the natural and bioactive molecules. PMID- 25140833 TI - c-CBL E3 ubiquitin ligase is overexpressed in cutaneous T-cell lymphoma: its inhibition promotes activation-induced cell death. AB - Mycosis fungoides and Sezary syndrome are two major forms of cutaneous T-cell lymphoma (CTCL) characterized by resistance to apoptosis. A central pathway for T cell apoptosis is activation-induced cell death, which is triggered through the T cell receptor (TCR). This results in upregulation of FAS ligand (FASL) and subsequent apoptosis through the FAS death receptor pathway. It has been known for more than a decade that TCR signaling is defective in CTCL; however, the underlying mechanism has not been apparent. In this report, we show that the E3 ubiquitin ligase, c-CBL, is overexpressed in CTCL and that its knockdown overcomes defective TCR signaling, resulting in phosphorylation of PLC-g1, calcium influx, ROS generation, upregulation of FASL, and extrinsic pathway apoptosis in CTCL cells expressing adequate FAS. In CTCL cells with suboptimal FAS expression, FAS can be upregulated epigenetically by derepression of the FAS promoter using methotrexate, which we showed previously has activity as a DNA methylation inhibitor. Using these combined strategies, FAS-low as well as FAS high CTCL cells can be killed effectively. PMID- 25140834 TI - Prussian blue-Au nanocomposites actuated hemin/G-quadruplexes catalysis for amplified detection of DNA, Hg2+ and adenosine triphosphate. AB - In this paper, horseradish peroxidase-mimicking DNAzyme (HRP-DNAzyme) and Prussian blue (PB)-gold (Au) nanocomposites were designed as versatile electrochemical sensing platforms for the amplified detection of DNA, Hg(2+) and adenosine triphosphate (ATP). By the conjugation of the target probe with the capture probe, a conformational change resulted in the formation of HRP-DNAzyme on the PB-Au modified electrode. The redox of HRP-DNAzyme (red) was efficiently carried out in the presence of H2O2, in which PB acted as a mediator stimulating the biocatalytic functions of HRP-DNAzyme and actuated a catalytic cycle bringing an amplified signal. Specific recognition of the target DNA, Hg(2+) and ATP allowed selective amperometric detection of the target molecule. The detection limits of DNA, Hg(2+) and ATP were 50 nM, 30 pM and 3 nM, respectively. The highlight of this work is that the catalytic cycle between PB-Au nanocomposites and HRP-DNAzyme was adequately utilized in the amplification platform for versatile sensing. The novel electrocatalytic biosensor involving only one-step incubation exhibited a wide linear range, low detection limit, and satisfactory selectivity and operational stability. The proposed approach provided an ease-of use and universal reporting system with a simple design and easy operations. PMID- 25140835 TI - A Nile Red/BODIPY-based bimodal probe sensitive to changes in the micropolarity and microviscosity of the endoplasmic reticulum. AB - We herein report a fluorescent bimodal probe (1) capable of determining ER viscosity and polarity changes using FLIM and fluorescence ratiometry, respectively; during ER stress caused by tunicamycin, the viscosity was increased from ca. 129.5 to 182.0 cP and the polarity of the ER (dielectric constant, epsilon) enhanced from 18.5 to 21.1. PMID- 25140836 TI - Effect of drainage on postoperative pain after laparoscopic ovarian cystectomy. AB - The aim of this prospective study was to investigate the effect of drainage on postoperative shoulder and abdominal pain after uncomplicated laparoscopic ovarian cystectomy (LOC). Allocation to drain or not to drain was non-randomised. There were 55 patients with drainage and 56 patients without drainage. Postoperative shoulder and abdominal pain was assessed using a 10-point visual analogue scale. Postoperative hospital stay in the drainage group was longer than the non-drainage group (p = 0.040). Postoperative shoulder pain scores at 6 h and 24 h were similar between the drainage and non-drainage groups (p = 0.376 and p = 0.847, respectively). Postoperative abdominal pain was higher in the drainage group at 6 h (p = 0.009), but was similar at 24 h (p = 0.097) between the groups. These data suggest that for LOC, drainage may not be useful to prevent postoperative shoulder pain and also increases postoperative abdominal pain and length of hospital stay. PMID- 25140838 TI - Synthesis of Au-decorated V2O5@ZnO heteronanostructures and enhanced plasmonic photocatalytic activity. AB - A ternary plasmonic photocatalyst consisting of Au-decorated V2O5@ZnO heteronanorods was successfully fabricated by an innovative four-step process: thermal evaporation of ZnO powders, CVD of intermediate on ZnO, solution deposition of Au NPs, and final thermal oxidization. SEM, TEM, EDX, XPS, and XRD analyses revealed that the interior cores and exterior shells of the as-prepared heteronanorods were single-crystal wurtzite-type ZnO and polycrystalline orthorhombic V2O5, respectively, with a large quantity of Au NPs inlaid in the V2O5 shell. The optical properties of the ternary photocatalyst were investigated in detail and compared with those of bare ZnO and V2O5@ZnO. UV-vis absorption spectra of ZnO, V2O5@ZnO, and Au-decorated V2O5@ZnO showed gradually enhanced absorption in the visible region. In addition, gradually decreased emission intensity was also observed in the photoluminescence (PL) spectra, revealing enhanced charge separation efficiency. Because of these excellent qualities, the photocatalytic behavior of the ternary photocatalyst was studied in the photodegradation of methylene blue under UV-vis irradiation, which showed an enhanced photodegradation rate nearly 7 times higher than that of bare ZnO and nearly 3 times higher than that of V2O5@ZnO, mainly owing to the enlarged light absorption region, the effective electron-hole separation at the V2O5-ZnO and V2O5-Au interfaces, and strong localization of plasmonic near-field effects. PMID- 25140837 TI - The parametric g-formula for time-to-event data: intuition and a worked example. AB - BACKGROUND: The parametric g-formula can be used to estimate the effect of a policy, intervention, or treatment. Unlike standard regression approaches, the parametric g-formula can be used to adjust for time-varying confounders that are affected by prior exposures. To date, there are few published examples in which the method has been applied. METHODS: We provide a simple introduction to the parametric g-formula and illustrate its application in an analysis of a small cohort study of bone marrow transplant patients in which the effect of treatment on mortality is subject to time-varying confounding. RESULTS: Standard regression adjustment yields a biased estimate of the effect of treatment on mortality relative to the estimate obtained by the g-formula. CONCLUSIONS: The g-formula allows estimation of a relevant parameter for public health officials: the change in the hazard of mortality under a hypothetical intervention, such as reduction of exposure to a harmful agent or introduction of a beneficial new treatment. We present a simple approach to implement the parametric g-formula that is sufficiently general to allow easy adaptation to many settings of public health relevance. PMID- 25140839 TI - Genipin cross-linked nanocomposite films for the immobilization of antimicrobial agent. AB - Cellulose nanocrystal (CNC) reinforced chitosan based antimicrobial films were prepared by immobilizing nisin on the surface of the films. Nanocomposite films containing 18.65 MUg/cm(2) of nisin reduced the count of L. monocytogenes by 6.73 log CFU/g, compared to the control meat samples (8.54 log CFU/g) during storage at 4 degrees C in a Ready-To-Eat (RTE) meat system. Film formulations containing 9.33 MUg/cm(2) of nisin increased the lag phase of L. monocytogenes on meat by more than 21 days, whereas formulations with 18.65 MUg/cm(2) completely inhibited the growth of L. monocytogenes during storage. Genipin was used to cross-link and protect the activity of nisin during storage. Nanocomposite films cross-linked with 0.05% w/v genipin exhibited the highest bioactivity (10.89 MUg/cm(2)) during the storage experiment, as compared to that of the un-cross-linked films (7.23 MUg/cm(2)). Genipin cross-linked films were able to reduce the growth rate of L. monocytogenes on ham samples by 21% as compared to the un-cross-linked films. Spectroscopic analysis confirmed the formation of genipin-nisin-chitosan heterocyclic cross-linked network. Genipin cross-linked films also improved the swelling, water solubility, and mechanical properties of the nanocomposite films. PMID- 25140840 TI - Stress and resilience in military mortuary workers: care of the dead from battlefield to home. AB - The death of a military service member in war provokes feelings of distress and pride in mortuary workers who process the remains. To further understand their reactions, the authors interviewed 34 military and civilian personnel to learn more about their work stresses and rewards. They review stresses of anticipation, exposure, and experience in handling the dead and explore the personal, supervisory, and leadership strategies to reduce negative effects and promote personal growth. These results can be applied to many other situations requiring planning, implementing, and supervising mortuary operations involving mass death. PMID- 25140842 TI - Reconstructing fungal natural product biosynthetic pathways. AB - Large scale fungal genome sequencing has revealed a multitude of potential natural product biosynthetic pathways that remain uncharted. Here we describe some of the methods that have been used to explore them via heterologous gene expression. We focus on filamentous fungal hosts and discuss the technological challenges and successes behind the reconstruction of fungal natural product pathways. Optimised, efficient heterologous expression of reconstructed biosynthetic pathways promises progress in the discovery of novel compounds that could be utilised by the pharmaceutical and agrochemical industries. PMID- 25140844 TI - Managing corneal abrasions in primary care. AB - Corneal abrasion is a common eye injury that occurs in all age-groups. A focused history and physical exam can identify patients with corneal abrasions and improve intervention time. Minor corneal abrasions usually heal within 48 hours without complications or eye damage. PMID- 25140843 TI - Does prenatal exposure to vitamin D-fortified margarine and milk alter birth weight? A societal experiment. AB - The present study examined whether exposure to vitamin D from fortified margarine and milk during prenatal life influenced mean birth weight and the risk of high or low birth weight. The study was based on the Danish vitamin D fortification programme, which was a societal intervention with mandatory fortification of margarine during 1961-1985 and voluntary fortification of low-fat milk between 1972 and 1976. The influence of prenatal vitamin D exposure on birth weight was investigated among 51 883 Danish children, by comparing birth weight among individuals born during 2 years before or after the initiation and termination of vitamin D fortification programmes. In total, four sets of analyses were performed. Information on birth weight was available in the Copenhagen School Health Record Register for all school children in Copenhagen. The mean birth weight was lower among the exposed than non-exposed children during all study periods (milk initiation - 20.3 (95 % CI - 39.2, - 1.4) g; milk termination - 25.9 (95 % CI - 46.0, - 5.7) g; margarine termination - 45.7 (95 % CI - 66.6, - 24.8) g), except during the period around the initiation of margarine fortification, where exposed children were heavier than non-exposed children (margarine initiation 27.4 (95 % CI 10.8, 44.0) g). No differences in the odds of high (>4000 g) or low ( < 2500 g) birth weight were observed between the children exposed and non-exposed to vitamin D fortification prenatally. Prenatal exposure to vitamin D from fortified margarine and milk altered birth weight, but the effect was small and inconsistent, reaching the conclusion that vitamin D fortification seems to be clinically irrelevant in relation to fetal growth. PMID- 25140845 TI - Simeprevir for hepatitis C virus. PMID- 25140846 TI - Essential tremor versus Parkinson disease: Make the right diagnosis. PMID- 25140847 TI - Infective endocarditis: Beyond TEE. PMID- 25140848 TI - Advocacy can overcome acts of derision. PMID- 25140851 TI - Connecting with chronically ill patients to improve treatment adherence. AB - This study presents an integrative review of the literature assessing the relationships among a patient's style in coping with a long-term health condition, the patient-practitioner therapeutic alliance, and treatment adherence among chronically ill adults. Evidence-based recommendations to improve nurse practitioner-patient therapeutic alliance and treatment adherence are suggested. PMID- 25140852 TI - Preexposure prophylaxis: An emerging clinical approach to preventing HIV in high risk adults. AB - The HIV antiretroviral drug emtricitabine/tenofovir disoproxil fumarate (Truvada) was recently approved as preexposure prophylaxis (PrEP) therapy for adults at high risk for sexually acquired HIV infection. This article reviews the data supporting the efficacy of PrEP, and provides other relevant data regarding the implementation of PrEP. PMID- 25140854 TI - Phytomonitoring of chlorinated ethenes in trees: a four-year study of seasonal chemodynamics in planta. AB - Long-term monitoring (LTM) of groundwater remedial projects is costly and time consuming, particularly when using phytoremediation, a long-term remedial approach. The use of trees as sensors of groundwater contamination (i.e., phytoscreening) has been widely described, although the use of trees to provide long-term monitoring of such plumes (phytomonitoring) has been more limited due to unexplained variability of contaminant concentrations in trees. To assess this variability, we developed an in planta sampling method to obtain high-frequency measurements of chlorinated ethenes in oak (Quercus rubra) and baldcypress (Taxodium distichum) trees growing above a contaminated plume during a 4-year trial. The data set revealed that contaminant concentrations increased rapidly with transpiration in the spring and decreased in the fall, resulting in perchloroethene (PCE) and trichloroethene (TCE) sapwood concentrations an order of magnitude higher in late summer as compared to winter. Heartwood PCE and TCE concentrations were more buffered against seasonal effects. Rainfall events caused negligible dilution of contaminant concentrations in trees after precipitation events. Modeling evapotranspiration potential from meteorological data and comparing the modeled uptake and transport with the 4 years of high frequency data provides a foundation to advance the implementation of phytomonitoring and improved understanding of plant contaminant interactions. PMID- 25140856 TI - Ebola virus disease in West Africa--no early end to the outbreak. PMID- 25140855 TI - The international Ebola emergency. PMID- 25140857 TI - Studying "secret serums"--toward safe, effective Ebola treatments. PMID- 25140858 TI - Ebola 2014--new challenges, new global response and responsibility. PMID- 25140859 TI - Women more vulnerable than men when facing risk for treatment-induced infertility: a qualitative study of young adults newly diagnosed with cancer. AB - BACKGROUND: Being diagnosed with cancer constitutes not only an immediate threat to health, but cancer treatments may also have a negative impact on fertility. Retrospective studies show that many survivors regret not having received fertility-related information and being offered fertility preservation at time of diagnosis. This qualitative study investigates newly diagnosed cancer patients' experiences of fertility-related communication and how they reason about the risk of future infertility. MATERIAL AND METHODS: Informants were recruited at three cancer wards at a university hospital. Eleven women and 10 men newly diagnosed with cancer participated in individual semi-structured interviews focusing on three domains: experiences of fertility-related communication, decision-making concerning fertility preservation, and thoughts and feelings about the risk of possible infertility. Data was analyzed through qualitative content analysis. RESULTS: The analysis resulted in three sub-themes, 'Getting to know', 'Reacting to the risk' and 'Handling uncertainty', and one main theme 'Women more vulnerable when facing risk for infertility', indicating that women reported more negative experiences related to patient-provider communication regarding fertility-related aspects of cancer treatment, as well as negative emotional reactions to the risk of infertility and challenges related to handling uncertainty regarding future fertility. The informants described distress when receiving treatment with possible impact on fertility and used different strategies to handle the risk for infertility, such as relying on fertility preservation or thinking of alternative ways to achieve parenthood. The negative experiences reported by the female informants may be related to the fact that none of the women, but almost all men, had received information about and used fertility preservation. CONCLUSIONS: Women newly diagnosed with cancer seem to be especially vulnerable when facing risk for treatment-induced infertility. Lack of shared decision-making concerning future fertility may cause distress and it is therefore necessary to improve the fertility-related communication targeted to female cancer patients. PMID- 25140860 TI - Outcomes of stereotactic radiotherapy for cranial and extracranial metastatic renal cell carcinoma: a systematic review. AB - BACKGROUND: Stereotactic radiotherapy is a non-invasive, ablative technique which may be particularly effective in treating metastatic renal cell carcinoma (RCC). The study objective was to analyse outcomes and toxicity of stereotactic radiotherapy in metastatic RCC. MATERIAL AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of Medline was performed in March 2013. Exclusion criteria included mixed histology studies and case series. Local control, overall survival and toxicities were analysed. RESULTS: From 148 publications identified, 16 and 10 publications for cranial and extracranial metastatic RCC met inclusion criteria, respectively. There were 810 intracranial patients and 2433 targets. The weighted local control was 92%. Overall survival ranged from 6.7 to 25.6 months. Significant Grade 3-4 toxicity ranged from 0% to 6%. The weighted rate of treatment-related mortality was 0.6%, all secondary to intratumoral haemorrhage. There were 389 extracranial patients and 730 targets. The weighted local control was 89%. Median overall survival ranged from 11.7 to 22 months. Grade 3-4 toxicity ranged from 0% to 4%. Treatment-related mortality was 0.5%. CONCLUSION: Stereotactic radiotherapy is associated with excellent local control and low rates of toxicity for intracranial and extracranial metastatic RCC. Future randomised studies are required to confirm the additional benefit of Stereotactic Ablative Body Radiotherapy (SABR) above standard conservative or palliative approaches. PMID- 25140861 TI - Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. AB - BACKGROUND: The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classification has resulted in a new nomenclature dividing NENs into neuroendocrine tumours (NETs) including G1 (Ki67 index <= 2%) and G2 (Ki67 index 3-20%) tumours and neuroendocrine carcinomas (NECs) with Ki67 index > 20%, G3. Aim. These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients. PMID- 25140862 TI - Fatigue in male lymphoma survivors differs between diagnostic groups and is associated with latent hypothyroidism. AB - BACKGROUND: Few studies have explored fatigue in different groups of lymphoma survivors and the association with hormonal dysfunctions. The aims were to analyze associations between fatigue and thyroid and gonadal function in male lymphoma survivors. In addition, the impact of chronic fatigue on work situation and daily functioning were explored. PATIENTS AND METHODS: This cross-sectional study included male lymphoma survivors diagnosed in 1980-2002, aged <= 50 years at diagnosis and > 18 years at survey in 2007. The participants (n = 233, median age at survey: 48 years, median observation time: 15 years) completed questionnaires assessing levels of fatigue, chronic fatigue (duration >= 6 months), mental distress, daily functioning and work situation. Levels of thyroid and gonadal hormones were assessed. The participants were grouped according to diagnosis: Hodgkin lymphoma (HL, n = 131), aggressive/very aggressive non-Hodgkin lymphoma (NHL) (n = 67) and indolent NHL (n = 35). Thyroid hormones were categorized as normal (n = 174) or latent hypothyroidism (elevated thyroid stimulating hormone, n = 59). Gonadal hormones were categorized as normal (n = 111), elevated follicle stimulating hormone only (n = 45), primary (n = 35) or secondary hypogonadism (n = 42). Uni- and multivariate regression analyses were performed. A p value < 0.05 indicated the level of significance. RESULTS: The survivors of HL and aggressive/very aggressive NHL had similar fatigue levels and similar prevalence of chronic fatigue (HL: 31%, aggressive/very aggressive; NHL: 27%). Survivors of indolent NHL had lower fatigue levels and prevalence of chronic fatigue (11%). Latent hypothyroidism was associated with increased fatigue levels (p = 0.042). Gonadal function was not associated with levels of fatigue or chronic fatigue. Mental distress was associated with increasing fatigue levels and chronic fatigue (p < 0.001). We found negative associations between chronic fatigue, daily functioning and work status. CONCLUSIONS: Fatigued lymphoma survivors should be investigated for thyroid function. The negative impact of chronic fatigue on daily functioning and work status emphasizes the importance of maintaining the effort in understanding the mechanisms behind fatigue. PMID- 25140863 TI - Comparison of bilateral and unilateral contractions between swimmers and nonathletes during leg press and hand grip exercises. AB - The bilateral limb deficit (BLD) is defined as the reduction in force production during bilateral compared with summed unilateral contractions of homologous muscles. The underlying mechanism for the BLD has been elusive to determine. The purpose of this study was to examine the presence of the BLD during maximal isometric leg press and handgrip exercises in female swimmers (n = 9, mean age = 20.1 +/- 1.3 years) and nonathletes (n = 9, mean age = 21.7 +/- 1.3 years) to gain further insight into this phenomenon. Force and electromyography (EMG) measures were collected from participants under bilateral and unilateral conditions for handgrip and leg press exercises. Bilateral limb ratios (BLR) were calculated for swimmers (BLRS) and nonathletes (BLRNA). A deficit was found for swimmers and nonathletes in leg force (BLRS = 79.84% +/- 13.09% and BLRNA = 81.44% +/- 19.23%) and leg EMG (BLRS = 88.45% +/- 15.41% and BLRNA = 94.66% +/- 13.62%); however, no BLD was seen in hand force (BLRS = 98.30% +/- 11.21% and BLRNA = 95.91% +/- 11.04%) and hand EMG (BLRS = 102.42% +/- 11.20% and BLRNA = 103.30% +/- 16.50%). Furthermore, no significant differences were found between groups for leg force, leg EMG, hand force, and hand EMG. In conclusion, a BLD was detected for both groups during bilateral isometric leg press. This suggests that while the BLD may be affected by neural influences, there may other factors involved such as postural stability requirements to perform the exercise. PMID- 25140864 TI - TGFbeta: A player on multiple fronts in the tumor microenvironment. AB - The physiological functions of transforming growth factor (TGF)-beta in cell signaling include regulation of developmental processes and cell growth. Tumor cells very often display altered regulation of the TGFbeta signaling pathway, either by defects in TGFbeta itself or in downstream components of the pathway. TGFbeta can play a dual role in tumorigenesis, i.e. it can be either tumor suppressive or tumor-promoting. TGFbeta suppresses the growth of tumor cells; however, in advanced tumors, it is associated with induction of progression, resulting in poor prognosis for patients. The TGFbeta negative regulation of cytotoxic cell function, together with the promotion of T-regulatory cell maturation, impairs anti-tumor responses. Recent studies have elucidated new roles for TGFbeta signaling in the tumor microenvironment. Abrogation of proper signaling induces epithelial-to-mesenchymal transition with pro-metastatic functions, resulting in cancer progression. Thus, TGFbeta signaling in the tumor microenvironment plays an important role in tumor initiation, progression, and metastasis by its capacity to regulate cross-talk between tumor cells and other components of the local environment. PMID- 25140865 TI - Ligand structures of synthetic deoxa-pyranosylamines with raucaffricine and strictosidine glucosidases provide structural insights into their binding and inhibitory behaviours. AB - Insight into the structure and inhibition mechanism of O-beta-d-glucosidases by deoxa-pyranosylamine type inhibitors is provided by X-ray analysis of complexes between raucaffricine and strictosidine glucosidases and N-(cyclohexylmethyl)-, N (cyclohexyl)- and N-(bromobenzyl)-beta-d-gluco-1,5-deoxa-pyranosylamine. All inhibitors anchored exclusively in the catalytic active site by competition with appropriate enzyme substrates. Thus facilitated prospective elucidation of the binding networks with residues located at <3.9 A distance will enable the development of potent inhibitors suitable for the production of valuable alkaloid glucosides, raucaffricine and strictosidine, by means of synthesis in Rauvolfia serpentina cell suspension cultures. PMID- 25140866 TI - Impact of acute guanfacine administration on stress and cue reactivity in cocaine dependent individuals. AB - BACKGROUND: Stress and drug-paired cues increase drug craving and noradrenergic activity in cocaine-dependent individuals. Thus, medications that attenuate noradrenergic activity may be effective therapeutic treatment options for cocaine dependent individuals. OBJECTIVES: To examine the impact of acute administration of the alpha2 adrenergic receptor agonist guanfacine on responses to multiple risk factors for relapse in cocaine-dependent individuals. METHODS: In a double blind, placebo-controlled study, cocaine-dependent individuals (n = 84), were randomized to receive either 2 mg guanfacine (n = 50) or placebo (n = 34). Within each treatment arm, subjects were randomized to either a stress (guanfacine n = 26; placebo n = 15) or a no-stress (guanfacine n = 24; placebo n = 19) group. Participants in the stress group performed the Trier Social Stress Test. Subjects in each group were exposed to a neutral cue and then to cocaine-related cues. Plasma cortisol and subjective responses were compared between the four groups. RESULTS: The no-stress guanfacine group reported greater craving in response to cocaine cues as compared to the neutral cue (p < 0.001). The guanfacine stress group reported greater subjective stress at the neutral cue than at baseline (p = 0.032). The cocaine cue increased subjective stress in the guanfacine (p < 0.001) no-stress group. There were no effects of guanfacine on cortisol levels in either the stress or no stress groups (all p > 0.70). CONCLUSION: This study found no effects of a single 2 mg dose of guanfacine on reactivity to stress and cues alone or on the interaction of stress and drug cues. In cocaine-dependent individuals an acute 2 mg dose of guanfacine may not be an effective therapeutic treatment strategy. PMID- 25140867 TI - The potential role of anticoagulant therapy for the secondary prevention of ischemic events post-acute coronary syndrome. AB - Abstract The use of dual antiplatelet therapy has led to a substantial reduction in ischemic events post-acute coronary syndrome (ACS). Despite this, recurrent event rates remain high. Recent research has combined antiplatelet with anticoagulant therapy to reduce recurrent event rates further. Compared with standard medical therapy, rivaroxaban demonstrated improved efficacy outcomes and significantly reduced mortality after an ACS. Although clear benefits of novel oral anticoagulants post-ACS have been proven, concerns regarding bleeding are still a barrier to widespread use. This review explores key trials of dual antiplatelet therapy and examines the latest research in anticoagulation aiming to optimize clinical outcomes post-ACS. PMID- 25140868 TI - Non-occupational post-exposure prophylaxis for HIV: 10-year retrospective analysis in Seattle, Washington. AB - Despite treatment guidelines in place since 2005, non-occupational post-exposure HIV prophylaxis (nPEP) remains an underutilized prevention strategy. We conducted a retrospective chart review of patients presenting to a publicly-funded HIV clinic in Seattle, Washington for nPEP between 2000 and 2010 (N = 360). nPEP prescriptions were provided for 324 (90%) patients; 83% of prescription decisions were appropriate according to Centers for Disease Control and Prevention guidelines, but only 31% (N = 111/360) of patients were considered "high risk." In order to use limited resources most efficiently, public health agencies should target messaging for this high-cost intervention to individuals with high-risk HIV exposures. PMID- 25140869 TI - Dental auxiliaries for dental care traditionally provided by dentists. AB - BACKGROUND: Poor or inequitable access to oral health care is commonly reported in high-, middle- and low-income countries. Although the severity of these problems varies, a lack of supply of dentists and their uneven distribution are important factors. Delegating care to dental auxiliaries could ease this problem, extend services to where they are unavailable and liberate time for dentists to do more complex work. Before such an approach can be advocated, it is important to know the relative effectiveness of dental auxiliaries and dentists. OBJECTIVES: To assess the effectiveness, costs and cost effectiveness of dental auxiliaries in providing care traditionally provided by dentists. SEARCH METHODS: We searched the following electronic databases from their inception dates up to November 2013: the Cochrane Effective Practice and Organisation of Care (EPOC) Group's Specialised Register; Cochrane Oral Health Group's Specialised Register; the Cochrane Central Register of Controlled Trials (Issue 11, 2013); MEDLINE; EMBASE; CINAHL; Cochrane Database of Systematic Reviews; Database of Abstracts of Reviews of Effectiveness; five other databases and two trial registries. We also undertook a grey literature search and searched the reference list of included studies and contacted authors of relevant papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs), non-randomised controlled clinical trials (NRCTs), interrupted time series (ITSs) and controlled before and after studies (CBAs) evaluating the effectiveness of dental auxiliaries compared with dentists in undertaking clinical tasks traditionally performed by a dentist. DATA COLLECTION AND ANALYSIS: Three review authors independently applied eligibility criteria, extracted data and assessed the risk of bias of each included study and two review authors assessed the quality of the evidence from the included studies, according to The Cochrane Collaboration's procedures. Since meta analysis was not possible, we gave a narrative description of the results. MAIN RESULTS: We identified five studies (one cluster RCT, three RCTs and one NRCT), evaluating the effectiveness of dental auxiliaries compared with dentists in providing dental care traditionally provided by dentists, eligible for inclusion in this review. The included studies, which involved 13 dental auxiliaries, six dentists, and more than 1156 participants, evaluated two clinical tasks/techniques: placement of preventive resin fissure sealants and the atraumatic restorative technique (ART). Two studies were conducted in the US, and one each in Canada, Gambia and Singapore.Of the four studies evaluating effectiveness in placing preventive resin fissure sealants, three found no evidence of a difference in retention rates of those placed by dental auxiliaries and dentists over a range of follow-up periods (six to 24 months). One study found that fissure sealants placed by a dental auxiliary had lower retention rates than one placed by a dentist after 48 months (9.0% with auxiliary versus 29.1% with dentist). The same study reported that the net reduction after 48 months in the number teeth exhibiting caries (dental decay) was lower for teeth treated by the dental auxiliary than the dentist (3 with auxiliary versus 60 with dentist, P value < 0.001).One study showed no evidence of a difference in dental decay after treatment with fissure sealants between groups. The one study comparing the effectiveness of dental auxiliaries and dentists in performing ART reported no difference in survival rates of the restorations (fillings) after 12 months.All studies were at high risk of bias and the overall quality of the evidence was very low, as assessed using the GRADE approach. In addition, four of the included studies were more than 20 years old; the materials used and the techniques assessed were out of date. We found no eligible studies comparing the effectiveness of dental auxiliaries and dentists in the diagnosis of oral diseases and conditions, in delivering oral health education and other aspects of health promotion, or studies assessing participants' perspectives including the acceptability of care received. None of the included studies reported adverse effects. In addition, we found no studies comparing the costs and cost effectiveness of dental auxiliaries and dentists, their impact on access and equity of access to care that met the pre-specified inclusion criteria. AUTHORS' CONCLUSIONS: We only identified five studies for inclusion in this review, all of which were at high risk of bias and four were published more than 20 years ago, highlighting the paucity of high-quality evaluations of the relative effectiveness, cost-effectiveness and safety of dental auxiliaries compared with dentists in performing clinical tasks. No firm conclusions could be drawn from the present review about the relative effectiveness of dental auxiliaries and dentists. PMID- 25140870 TI - Emotions under discussion: gender, status and communication in online collaboration. AB - BACKGROUND: Despite the undisputed role of emotions in teamwork, not much is known about the make-up of emotions in online collaboration. Publicly available repositories of collaboration data, such as Wikipedia editor discussions, now enable the large-scale study of affect and dialogue in peer production. METHODS: We investigate the established Wikipedia community and focus on how emotion and dialogue differ depending on the status, gender, and the communication network of the [Formula: see text] editors who have written at least 100 comments on the English Wikipedia's article talk pages. Emotions are quantified using a word based approach comparing the results of two predefined lexicon-based methods: LIWC and SentiStrength. PRINCIPAL FINDINGS: We find that administrators maintain a rather neutral, impersonal tone, while regular editors are more emotional and relationship-oriented, that is, they use language to form and maintain connections to other editors. A persistent gender difference is that female contributors communicate in a manner that promotes social affiliation and emotional connection more than male editors, irrespective of their status in the community. Female regular editors are the most relationship-oriented, whereas male administrators are the least relationship-focused. Finally, emotional and linguistic homophily is prevalent: editors tend to interact with other editors having similar emotional styles (e.g., editors expressing more anger connect more with one another). CONCLUSIONS/SIGNIFICANCE: Emotional expression and linguistic style in online collaboration differ substantially depending on the contributors' gender and status, and on the communication network. This should be taken into account when analyzing collaborative success, and may prove insightful to communities facing gender gap and stagnation in contributor acquisition and participation levels. PMID- 25140871 TI - Synthetic antibodies with a human framework that protect mice from lethal Sudan ebolavirus challenge. AB - The ebolaviruses cause severe and rapidly progressing hemorrhagic fever. There are five ebolavirus species; although much is known about Zaire ebolavirus (EBOV) and its neutralization by antibodies, little is known about Sudan ebolavirus (SUDV), which is emerging with increasing frequency. Here we describe monoclonal antibodies containing a human framework that potently inhibit infection by SUDV and protect mice from lethal challenge. The murine antibody 16F6, which binds the SUDV envelope glycoprotein (GP), served as the starting point for design. Sequence and structural alignment revealed similarities between 16F6 and YADS1, a synthetic antibody with a humanized scaffold. A focused phage library was constructed and screened to impart 16F6-like recognition properties onto the YADS1 scaffold. A panel of 17 antibodies were characterized and found to have a range of neutralization potentials against a pseudotype virus infection model. Neutralization correlated with GP binding as determined by ELISA. Two of these clones, E10 and F4, potently inhibited authentic SUDV and conferred protection and memory immunity in mice from lethal SUDV challenge. E10 and F4 were further shown to bind to the same epitope on GP as 16F6 with comparable affinities. These antibodies represent strong immunotherapeutic candidates for treatment of SUDV infection. PMID- 25140873 TI - The first ant-termite syninclusion in amber with CT-scan analysis of taphonomy. AB - We describe here a co-occurrence (i.e. a syninclusion) of ants and termites in a piece of Mexican amber (Totolapa deposit, Chiapas), whose importance is two-fold. First, this finding suggests at least a middle Miocene antiquity for the modern, though poorly documented, relationship between Azteca ants and Nasutitermes termites. Second, the presence of a Neivamyrmex army ant documents an in situ raiding behaviour of the same age and within the same community, confirmed by the fact that the army ant is holding one of the termite worker between its mandibles and by the presence of a termite with bitten abdomen. In addition, we present how CT-scan imaging can be an efficient tool to describe the topology of resin flows within amber pieces, and to point out the different states of preservation of the embedded insects. This can help achieving a better understanding of taphonomical processes, and tests ethological and ecological hypotheses in such complex syninclusions. PMID- 25140872 TI - Identity and specificity of Rhizoctonia-like fungi from different populations of Liparis japonica (Orchidaceae) in Northeast China. AB - Mycorrhizal association is known to be important to orchid species, and a complete understanding of the fungi that form mycorrhizas is required for orchid ecology and conservation. Liparis japonica (Orchidaceae) is a widespread terrestrial photosynthetic orchid in Northeast China. Previously, we found the genetic diversity of this species has been reduced recent years due to habitat destruction and fragmentation, but little was known about the relationship between this orchid species and the mycorrhizal fungi. The Rhizoctonia-like fungi are the commonly accepted mycorrhizal fungi associated with orchids. In this study, the distribution, diversity and specificity of culturable Rhizoctonia-like fungi associated with L. japonica species were investigated from seven populations in Northeast China. Among the 201 endophytic fungal isolates obtained, 86 Rhizoctonia-like fungi were identified based on morphological characters and molecular methods, and the ITS sequences and phylogenetic analysis revealed that all these Rhizoctonia-like fungi fell in the same main clade and were closely related to those of Tulasnella calospora species group. These findings indicated the high mycorrhizal specificity existed in L. japonica species regardless of habitats at least in Northeast China. Our results also supported the wide distribution of this fungal partner, and implied that the decline of L. japonica in Northeast China did not result from high mycorrhizal specificity. Using culture-dependent technology, these mycorrhizal fungal isolates might be important sources for the further utilizing in orchids conservation. PMID- 25140874 TI - Functional connectivity in the first year of life in infants at risk for autism spectrum disorder: an EEG study. AB - In the field of autism research, recent work has been devoted to studying both behavioral and neural markers that may aide in early identification of autism spectrum disorder (ASD). These studies have often tested infants who have a significant family history of autism spectrum disorder, given the increased prevalence observed among such infants. In the present study we tested infants at high- and low-risk for ASD (based on having an older sibling diagnosed with the disorder or not) at 6- and 12-months-of-age. We computed intrahemispheric linear coherence between anterior and posterior sites as a measure of neural functional connectivity derived from electroencephalography while the infants were listening to speech sounds. We found that by 12-months-of-age infants at risk for ASD showed reduced functional connectivity compared to low risk infants. Moreover, by 12-months-of-age infants later diagnosed with ASD showed reduced functional connectivity, compared to both infants at low risk for the disorder and infants at high risk who were not later diagnosed with ASD. Significant differences in functional connectivity were also found between low-risk infants and high-risk infants who did not go onto develop ASD. These results demonstrate that reduced functional connectivity appears to be related to genetic vulnerability for ASD. Moreover, they provide further evidence that ASD is broadly characterized by differences in neural integration that emerge during the first year of life. PMID- 25140875 TI - A biological micro actuator: graded and closed-loop control of insect leg motion by electrical stimulation of muscles. AB - In this study, a biological microactuator was demonstrated by closed-loop motion control of the front leg of an insect (Mecynorrhina torquata, beetle) via electrical stimulation of the leg muscles. The three antagonistic pairs of muscle groups in the front leg enabled the actuator to have three degrees of freedom: protraction/retraction, levation/depression, and extension/flexion. We observed that the threshold amplitude (voltage) required to elicit leg motions was approximately 1.0 V; thus, we fixed the stimulation amplitude at 1.5 V to ensure a muscle response. The leg motions were finely graded by alternation of the stimulation frequencies: higher stimulation frequencies elicited larger leg angular displacement. A closed-loop control system was then developed, where the stimulation frequency was the manipulated variable for leg-muscle stimulation (output from the final control element to the leg muscle) and the angular displacement of the leg motion was the system response. This closed-loop control system, with an optimized proportional gain and update time, regulated the leg to set at predetermined angular positions. The average electrical stimulation power consumption per muscle group was 148 uW. These findings related to and demonstrations of the leg motion control offer promise for the future development of a reliable, low-power, biological legged machine (i.e., an insect-machine hybrid legged robot). PMID- 25140876 TI - The effects of fluctuations in the nutrient supply on the expression of five members of the AGL17 clade of MADS-box genes in rice. AB - The ANR1 MADS-box gene in Arabidopsis is a key gene involved in regulating lateral root development in response to the external nitrate supply. There are five ANR1-like genes in Oryza sativa, OsMADS23, OsMADS25, OsMADS27, OsMADS57 and OsMADS61, all of which belong to the AGL17 clade. Here we have investigated the responsiveness of these genes to fluctuations in nitrogen (N), phosphorus (P) and sulfur (S) mineral nutrient supply. The MADS-box genes have been shown to have a range of responses to the nutrient supply. The expression of OsMADS61 was transiently induced by N deprivation but was not affected by re-supply with various N sources. The expression of OsMADS25 and OsMADS27 was induced by re supplying with NO3(-) and NH4NO3, but downregulated by NH4(+). The expression of OsMADS57 was significantly downregulated by N starvation and upregulated by 3 h NO3(-) re-supply. OsMADS23 was the only gene that showed no response to either N starvation nor NO3(-) re-supply. OsMADS57 was the only gene not regulated by P fluctuation whereas the expression of OsMADS23, OsMADS25 and OsMADS27 was downregulated by P starvation and P re-supply. In contrast, all five ANR1-related genes were significantly upregulated by S starvation. Our results also indicated that there were interactions among nitrate, sulphate and phosphate transporters in rice. PMID- 25140877 TI - Enhancing TB case detection: experience in offering upfront Xpert MTB/RIF testing to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug sensitive and drug resistant TB. AB - BACKGROUND: Diagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India. METHODS: The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm. RESULTS: 4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8-13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5-11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2-5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1-99.9), with no statistically significant variation with respect to past history of treatment. CONCLUSION: Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to present-day challenges in the diagnosis of PTB in pediatric patients. PMID- 25140878 TI - Elevated heart rate triggers action potential alternans and sudden death. translational study of a homozygous KCNH2 mutation. AB - BACKGROUND: Long QT syndrome (LQTS) leads to arrhythmic events and increased risk for sudden cardiac death (SCD). Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed "human HERG knockout" and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness. METHODS AND RESULTS: Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in silico mathematical modelling, protein biochemistry, confocal microscopy were performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation (p.R835Q) in the index patient (QTc ~506 ms with notched T waves). Parents were I degrees cousins - both heterozygous for the mutation and clinically unremarkable (QTc ~447 ms, father and ~396 ms, mother). Heterologous expression of KCNH2-R835Q showed mildly reduced current amplitudes. Biophysical properties of ionic currents were also only nominally changed with slight acceleration of deactivation and more negative V50 in R835Q-currents. Protein biochemistry and confocal microscopy revealed similar expression patterns and trafficking of WT and R835Q, even at elevated temperature. In silico analysis demonstrated mildly prolonged ventricular action potential duration (APD) compared to WT at a cycle length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT, but displayed APD alternans in R835Q. CONCLUSION: Kv11.1 channels affected by the C-terminal R835Q mutation display mildly modified biophysical properties, but leads to M-cell APD alternans with elevated heart rate and could precipitate SCD under specific clinical circumstances associated with high heart rates. PMID- 25140880 TI - A microfluidic linear node array for the study of protein-ligand interactions. AB - We have developed a microfluidic device for the continuous separation of small molecules from a protein mixture and demonstrated its practical use in the study of protein-ligand binding, a crucial aspect in drug discovery. Our results demonstrated dose-dependent binding between bovine serum albumin (BSA) and its small-molecule site marker, Eosin Y (EY), and found that the binding reached a plateau when the BSA : EY ratio was above 1, which agreed with the eosin binding capacity of BSA reported in literature. By streamline control using a combination of two fundamental building blocks (R and L nodes) with a microdevice operated at a high flow rate (up to 1300 MUL h(-1)), a solution barrier was created to "filter" off protein/protein-ligand complexes such that the small unbound molecules were isolated and quantified easily. The percentage decrease of small molecules with increasing protein concentration indicated the presence of binding events. Several fluorophores with different molecular weights were used to test the performance of the microfluidic "filter", which was tunable by 1) the total flow rate, and/or 2) the flow distribution ratio between the two device inlets; both were easily controllable by changing the syringe pump settings. Since the microdevice was operated at a relatively high flow rate, aliquots were easily recovered from the device outlets to facilitate off-chip detection. This microfluidic design is a novel and promising tool for preliminary drug screening. PMID- 25140881 TI - Unprecedented catalytic activity of Fe(NO3)3.9H2O: regioselective synthesis of 2 nitroimidazopyridines via oxidative amination. AB - A unique iron-catalyzed oxidative diamination of nitroalkene with 2-aminopyridine for the synthesis of 2-nitro-3-arylimidazo[1,2-a]pyridines with complete regioselectivity has been achieved under mild and aerobic reaction conditions. This is the first method for the synthesis of 2-nitroimidazo[1,2-a]pyridines. These scaffolds were also synthesized directly from styrenes. PMID- 25140882 TI - Biogeographic distribution patterns and their correlates in the diverse frog fauna of the Atlantic Forest hotspot. AB - Anurans are a highly diverse group in the Atlantic Forest hotspot (AF), yet distribution patterns and species richness gradients are not randomly distributed throughout the biome. Thus, we explore how anuran species are distributed in this complex and biodiverse hotspot, and hypothesize that this group can be distinguished by different cohesive regions. We used range maps of 497 species to obtain a presence/absence data grid, resolved to 50*50 km grain size, which was submitted to k-means clustering with v-fold cross-validation to determine the biogeographic regions. We also explored the extent to which current environmental variables, topography, and floristic structure of the AF are expected to identify the cluster patterns recognized by the k-means clustering. The biogeographic patterns found for amphibians are broadly congruent with ecoregions identified in the AF, but their edges, and sometimes the whole extent of some clusters, present much less resolved pattern compared to previous classification. We also identified that climate, topography, and vegetation structure of the AF explained a high percentage of variance of the cluster patterns identified, but the magnitude of the regression coefficients shifted regarding their importance in explaining the variance for each cluster. Specifically, we propose that the anuran fauna of the AF can be split into four biogeographic regions: a) less diverse and widely-ranged species that predominantly occur in the inland semideciduous forests; b) northern small-ranged species that presumably evolved within the Pleistocene forest refugia; c) highly diverse and small-ranged species from the southeastern Brazilian mountain chain and its adjacent semideciduous forest; and d) southern species from the Araucaria forest. Finally, the high congruence among the cluster patterns and previous eco-regions identified for the AF suggests that preserving the underlying habitat structure helps to preserve the historical and ecological signals that underlie the geographic distribution of AF anurans. PMID- 25140883 TI - Histogram flow mapping with optical coherence tomography for in vivo skin angiography of hereditary hemorrhagic telangiectasia. AB - Speckle statistics of flowing scatterers have been well documented in the literature. Speckle variance optical coherence tomography exploits the large variance values of intensity changes in time caused mainly by the random backscattering of light resulting from translational activity of red blood cells to map out the microvascular networks. A method to map out the microvasculature malformation of skin based on the time-domain histograms of individual pixels is presented with results obtained from both normal skin and skin containing vascular malformation. Results demonstrated that this method can potentially map out deeper blood vessels and enhance the visualization of microvasculature in low signal regions, while being resistant against motion (e.g., patient tremor or internal reflex movements). The overall results are manifested as more uniform en face projection maps of microvessels. Potential applications include clinical imaging of skin vascular abnormalities and wide-field skin angiography for the study of complex vascular networks. PMID- 25140884 TI - Multiphoton fluorescence lifetime imaging microscopy reveals free-to-bound NADH ratio changes associated with metabolic inhibition. AB - Measurement of endogenous free and bound NAD(P)H relative concentrations in living cells isa useful method for monitoring aspects of cellular metabolism, because the NADH/NAD+ reduction-oxidation pair is crucial for electron transfer through the mitochondrial electron transport chain. Variations of free and bound NAD(P)H ratio are also implicated in cellular bioenergetic and biosynthetic metabolic changes accompanying cancer. This study uses two-photon fluorescence lifetime imaging microscopy (FLIM) to investigate metabolic changes in MCF10A premalignant breast cancer cells treated with a range of glycolysis inhibitors: namely, 2 deoxy-D-glucose, oxythiamine, lonidamine, and 4-(chloromethyl) benzoyl chloride, as well as the mitochondrial membrane uncoupling agent carbonyl cyanide m-chlorophenylhydrazone. Through systematic analysis of FLIM data from control and treated cancer cells, we observed that all glycolytic inhibitors apart from lonidamine had a slightly decreased metabolic rate and that the presence of serum in the culture medium generally marginally protected cells from the effect of inhibitors. Direct production of glycolytic L-lactate was also measured in both treated and control cells. The combination of these two techniques gave valuable insights into cell metabolism and indicated that FLIM was more sensitive than traditional biochemical methods, as it directly measured metabolic changes within cells as compared to quantification of lactate secreted by metabolically active cells. PMID- 25140885 TI - Identification of kidney tumor tissue by infrared spectroscopy of extracellular matrix. AB - Fourier transform infrared (FT-IR) spectroscopy was applied to characterize the extracellular matrix (ECM) of kidney tumor tissue and normal kidney tissue. Freshly resected tissue samples from 31 patients were pressed on a CaF2 substrate. FT-IR spectra obtained from ECM of tumor tissue exhibit stronger absorption bands in the spectral region from 1000 to 1200 cm-1 and around 1750 cm 1 than those obtained from normal tissue. It is likely that the spectra of ECM of kidney tumor tissue with large increases in the intensities of these bands represent a higher concentration of fatty acids and glycerol. Amide I and amide II bands are stronger in the spectra of ECM from normal tissue, indicating a higher level of proteins. Our results suggest that FT-IR spectroscopy of the ECM is an innovative emerging technology for real-time intraoperative tumor diagnosis, which may improve margin clearance in renal cancer surgery. PMID- 25140886 TI - Suzuki-Miyaura cross-coupling reactions of unprotected haloimidazoles. AB - An efficient protocol for the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of unprotected haloimidazoles is reported. The relatively mild reaction conditions allow for ready access to a wide array of functionalized imidazole derivatives in good to excellent yields. The synthetic utility of this method is demonstrated by the total synthesis of nortopsentin D. PMID- 25140887 TI - Unexpected metal ion-assisted transformations leading to unexplored bridging ligands in Ni(II) coordination chemistry: the case of PO3F(2-) group. AB - The initial 'accidental', metal ion-assisted hydrolysis of PF6(-) to PO3F(2-) has been evolved in a systematic investigation of the bridging affinity of the latter group in Ni(II)/oximate chemistry; mono-, di- and trinuclear complexes have been prepared and confirmed both the rich reactivity of PO3F(2-) and its potential for further use as bridging ligand in high-nuclearity 3d-metal cluster chemistry. PMID- 25140888 TI - MicroRNAs as Mediators of the Ageing Process. AB - Human ageing is a complex and integrated gradual deterioration of cellular processes. There are nine major hallmarks of ageing, that include changes in DNA repair and DNA damage response, telomere shortening, changes in control over the expression and regulation of genes brought about by epigenetic and mRNA processing changes, loss of protein homeostasis, altered nutrient signaling, mitochondrial dysfunction, stem cell exhaustion, premature cellular senescence and altered intracellular communication. Like practically all other cellular processes, genes associated in features of ageing are regulated by miRNAs. In this review, I will outline each of the features of ageing, together with examples of specific miRNAs that have been demonstrated to be involved in each one. This will demonstrate the interconnected nature of the regulation of transcripts involved in human ageing, and the role of miRNAs in this process. Definition of the factors involved in degeneration of organismal, tissue and cellular homeostasis may provide biomarkers for healthy ageing and increase understanding of the processes that underpin the ageing process itself. PMID- 25140890 TI - Dynamic behavior of DNA cages anchored on spherically supported lipid bilayers. AB - We report the anchoring of 3D-DNA-cholesterol labeled cages on spherically supported lipid bilayer membranes (SSLBM) formed on silica beads, and their addressability through strand displacement reactions, controlled membrane orientation and templated dimerization. The bilayer-anchored cages can load three different DNA-fluorophores by hybridization to their "top" face (furthest from bilayer) and unload each of them selectively upon addition of a specific input displacement strand. We introduce a method to control strand displacement from their less accessible "bottom" face (closest to the bilayer), by adding cholesterol-substituted displacing strands that insert into the bilayer themselves in order to access the toehold region. The orientation of DNA cages within the bilayer is tunable by positioning multiple cholesterol anchoring units on the opposing two faces of the cage, thereby controlling their accessibility to proteins and enzymes. A population of two distinct DNA cages anchored to the SSLBMs exhibited significant membrane fluidity and have been directed into dimer assemblies on bilayer via input of a complementary linking strand. Displacement experiments performed on these anchored dimers indicate that removal of only one prism's anchoring cholesterol strand was not sufficient to release the dimers from the bilayer; however, removal of both cholesterol anchors from the dimerized prisms via two displacement strands cleanly released the dimers from the bilayer. This methodology allows for the anchoring of DNA cages on supported lipid bilayers, the control of their orientation and accessibility within the bilayer, and the programmable dimerization and selective removal of any of their components. The facile coupling of DNA to other functional materials makes this an attractive method for developing stimuli-responsive protein or nanoparticle arrays, drug releasing biomedical device surfaces and self-healing materials for light harvesting applications, using a highly modular, DNA-economic scaffold. PMID- 25140891 TI - Partial hydrogenation of a tetranuclear titanium nitrido complex with ammonia borane. AB - The treatment of [{Ti(eta(5)-C5Me5)}4(MU3-N)4] with NH3BH3 leads to the paramagnetic imidonitrido complex [{Ti(eta(5)-C5Me5)}4(MU3-N)3(MU3-NH)], which can also be obtained by stepwise proton and electron transfer with HOTf and [K(C5Me5)]. PMID- 25140889 TI - 4-1BBL enhances CD8+ T cell responses induced by vectored vaccines in mice but fails to improve immunogenicity in rhesus macaques. AB - T cells play a central role in the immune response to many of the world's major infectious diseases. In this study we investigated the tumour necrosis factor receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its ability to increase T cell immunogenicity induced by a variety of recombinant vectored vaccines. To efficiently test this hypothesis, we assessed a number of promoters and developed a stable bi-cistronic vector expressing both the antigen and adjuvant. Co-expression of 4-1BBL, together with our model antigen TIP, was shown to increase the frequency of murine antigen-specific IFN-gamma secreting CD8(+) T cells in three vector platforms examined. Enhancement of the response was not limited by co-expression with the antigen, as an increase in CD8(+) immunogenicity was also observed by co-administration of two vectors each expressing only the antigen or adjuvant. However, when this regimen was tested in non-human primates using a clinical malaria vaccine candidate, no adjuvant effect of 4-1BBL was observed limiting its potential use as a single adjuvant for translation into a clinical vaccine. PMID- 25140892 TI - Exonuclease III-assisted cascade signal amplification strategy for label-free and ultrasensitive chemiluminescence detection of DNA. AB - Detection of ultralow concentrations of specific nucleic acid sequences is a central challenge in the early diagnosis of genetic diseases and biodefense applications. Herein, we report a simple and homogeneous chemiluminescence (CL) method for ultrasensitive DNA detection. It is based on the exonuclease III (Exo III)-assisted cascade signal amplification and the catalytic effect of G quadruplex-hemin DNAzyme on the luminol-H2O2 CL system. A quadruplex-forming DNA probe hybridizes a hairpin DNA probe to construct a duplex DNA probe as recognition element. Upon sensing of target DNA, the recognition of target DNA and the duplex DNA probe triggers the Exo III cleavage process, accompanied by releasing target DNA and generating a new secondary target DNA fragment. The released target DNA and the secondary target DNA are recycled. Simultaneously, numerous quadruplex-forming sequences are liberated and bind hemin to yield G quadruplex-hemin DNAzyme, which subsequently catalyze the luminol-H2O2 reaction to produce strong CL emission. This method exhibited a high sensitivity toward target DNA with a detection limit of 8 fM, which was about 100 times lower than that of the reported DNAzyme-based colorimetric system for DNA detection with Exo III-assisted cascade signal amplification. This method provides a simple, isothermal, and low-cost approach for sensitive detection of DNA and holds a great potential for early diagnosis in gene-related diseases. PMID- 25140893 TI - Uterine leiomyomas with bizarre nuclei: a clinicopathologic study of 59 cases. AB - Leiomyoma with bizarre nuclei (LM-BN) is an uncommon tumor with histologic features (mononucleated or multinucleated bizarre cells that may have a diffuse distribution, prominent nucleoli, and karyorrhectic nuclei that may mimic atypical mitoses) that often causes confusion with leiomyosarcoma. Fifty-nine LM BNs were collected from our consultation files over the years 2000 to 2011. Features recorded included patient age, therapy, tumor size, border, gross appearance, density and distribution of BN, mitotic count, karyorrhectic nuclei, prominent nucleoli, cells with conspicuous dense eosinophilic cytoplasm (rhabdoid like), vascular changes and type of vasculature, and presence of necrosis and its nature. Follow-up information was obtained for all patients. Patients ranged in age from 25 to 75 (average 45) years (11 patients between 25 and 35 y, 20 between 36 and 45 y, 22 between 46 and 55 y, and 6 between 56 and 75 y). Forty-two underwent hysterectomy and 17 myomectomy. For 51 tumors gross findings were known. Forty (78%) had a solid white and whorled cut surface and 11 (22%) a yellow appearance. Five (10%) neoplasms showed prominent cystic degeneration, and hemorrhage and/or necrosis was seen in 9 (18%). Forty-five LM-BNs had a pushing margin with the surrounding myometrium, whereas 1 showed irregular borders. Margins could not be ascertained in the slides available in 13 cases. Twenty eight (48%), 19 (32%), and 12 (20%) LM-BN showed low, intermediate, and high BN density. Eighteen (30%) tumors showed diffuse, 26 (44%) showed multifocal, and 15 (26%) had focal BN distribution. Mitotic counts ranged from 0 to 7/10 high-power fields (HPF) (average 1 to 2/10 HPF). Thirty-seven (63%) had <2/10 HPF, 19 (32%) had 2 to 5 mitoses/10 HPF, and in 3 tumors (5%) mitotic counts were 6, 7, and 7/10 HPF (2 with focal and 1 with diffuse BN). All but 4 LM-BNs showed karyorrhectic nuclei, striking in 12 neoplasms, mimicking atypical mitoses. Nineteen (32%) LMs had prominent eosinophilic nucleoli surrounded by a clear halo. Ischemic necrosis was detected in 21 (36%) LM-BN. Rhabdoid-like cells were noted in 24 (41%) tumors. All patients had no evidence of recurrence, ranging from 1 to 13 years (overall average 6 y; in patients with myomectomy 6.3 y with a range of 2.6 to 11 y). Our results corroborate that LM-BN is associated with a favorable outcome even in those patients only treated by myomectomy and highlights that a conservative approach can be undertaken in these patients, as many of them are of reproductive age. Because of the favorable outcome, the term LM-BN is preferable to alternative terminology including "atypical leiomyoma." PMID- 25140894 TI - Assessment of tumor regression of esophageal adenocarcinomas after neoadjuvant chemotherapy: comparison of 2 commonly used scoring approaches. AB - Histopathologic determination of tumor regression provides important prognostic information for locally advanced gastroesophageal carcinomas after neoadjuvant treatment. Regression grading systems mostly refer to the amount of therapy induced fibrosis in relation to residual tumor or the estimated percentage of residual tumor in relation to the former tumor site. Although these methods are generally accepted, currently there is no common standard for reporting tumor regression in gastroesophageal cancers. We compared the application of these 2 major principles for assessment of tumor regression: hematoxylin and eosin stained slides from 89 resection specimens of esophageal adenocarcinomas following neoadjuvant chemotherapy were independently reviewed by 3 pathologists from different institutions. Tumor regression was determined by the 5-tiered Mandard system (fibrosis/tumor relation) and the 4-tiered Becker system (residual tumor in %). Interobserver agreement for the Becker system showed better weighted kappa values compared with the Mandard system (0.78 vs. 0.62). Evaluation of the whole embedded tumor site showed improved results (Becker: 0.83; Mandard: 0.73) as compared with only 1 representative slide (Becker: 0.68; Mandard: 0.71). Modification into simplified 3-tiered systems showed comparable interobserver agreement but better prognostic stratification for both systems (log rank Becker: P=0.015; Mandard P=0.03), with independent prognostic impact for overall survival (modified Becker: P=0.011, hazard ratio=3.07; modified Mandard: P=0.023, hazard ratio=2.72). In conclusion, both systems provide substantial to excellent interobserver agreement for estimation of tumor regression after neoadjuvant chemotherapy in esophageal adenocarcinomas. A simple 3-tiered system with the estimation of residual tumor in % (complete regression/1% to 50% residual tumor/>50% residual tumor) maintains the highest reproducibility and prognostic value. PMID- 25140895 TI - Metastatic renal cell carcinoma to the urinary bladder: a report of 11 cases. AB - Metastatic renal cell carcinoma (RCC) to the urinary bladder is rarely seen. Herein, we report the histologic subtypes, immunohistochemical characteristics, and prognosis of 11 patients with metastatic RCC to the urinary bladder. The mean age at the time of diagnosis of metastatic RCC to the bladder was 66 years (range, 58 to 79 y). There were 9 male and 2 female patients. Four patients presented with hematuria, 2 with urinary retention/obstruction, and 1 with bladder calculi. Four patients were asymptomatic and presented for surveillance cystoscopy, wherein they were found to have bladder masses. Nine patients had prior histories of RCC. The remaining 2 patients presented with metastatic clear cell RCC to the bladder and were subsequently found to have renal masses. The average time between nephrectomy and metastasis to the bladder was 20.7 months (range, 0 to 87 mo). Of the 10 patients with radical/partial nephrectomy, 7 cases were clear cell (2 with sarcomatoid features), 2 papillary, and 1 chromophobe with histologic fidelity between the primary and metastasis. Of cases with available data, the primaries' ISUP nucleolar grades were 2 (n=2), 3 (n=4), and 4 for the 2 cases with sarcomatoid features. In 8 cases, the bladder RCC undermined overlying urothelium with extensive urothelial denudation, and in 3 cases the RCC was free floating without attachment to the urothelium. The 1 chromophobe RCC metastasized with pagetoid spread to a preexisting urothelial papilloma. PAX8 immunohistochemistry was used to confirm the diagnosis in 2 cases. Three patients have no evidence of disease (7, 9, and 13 mo). Two are alive with disease after chemotherapy (30, 37 mo). Six patients are dead of disease with multiorgan metastases; 4 are dead after therapy (5, 8, 25, 28 mo), and two died without radiation or chemotherapy at 10 and 71 months. Metastatic RCC to the urinary bladder is uncommon, with most cases clear cell RCC. In some cases, evidence supports "drop metastases" as the mechanism of spread and patients have relatively long survival. However, in other cases spread to the bladder is in the setting of metastases to other sites, and these patients tended to die relatively shortly after their bladder metastases. PMID- 25140896 TI - Chemical vapor deposition of twisted bilayer and few-layer MoSe2 over SiO(x) substrates. AB - The chemical vapor deposition of monolayer and few-layer transition metal dichalcogenides is a rapidly developing area of materials science due to the exciting electrical, optical, thermal and mechanical properties of transition metal dichalcogenides in their layered form. These properties make these innovative materials potentially relevant to wide-ranging commercial applications. One of these promising materials is MoSe2; however, just recently, a few research groups have been able to demonstrate its synthesis via chemical vapor deposition. Moreover, only oriented few-layer MoSe2 has been exhibited by synthetically formed material using chemical vapor deposition thus far. Here, we confirm twisted-layer MoSe2 can also form during chemical vapor deposition. Twisted-layer transition metal dichalcogenides alter their properties as compared to their oriented counterparts. Therefore, twisted-layer structures are of interest because they can tune their properties. PMID- 25140897 TI - Magnetically stabilized Fe8(MU4-S)6S8 clusters in Ba6Fe25S27. AB - We have prepared Ba6Fe25S27, and studied its magnetic properties and electronic structure. Single crystal diffraction revealed a cubic phase (Pm3[combining macron]m) with a = 10.2057(9) A and Z = 1. Within the large cubic cell, tetrahedrally coordinated Fe atoms arrange into octonuclear Fe8(MU4-S)6(S8) clusters, which can be described as a cube of Fe atoms with six face-capping and eight terminal S atoms. SQUID magnetometry measurements reveal an antiferromagnetic transition at 25 K and anomalous high-temperature dependence of magnetic susceptibility that is non-Curie like-two magnetic signatures which mimic behavior seen in the parent phases of Fe-based superconductors. Using a combined DFT and molecular orbital based approach, we provide an interpretation of the bonding and stability within Ba6M25S27 (M = Fe, Co, Ni) and related M9S8 phases. Through a sigma-bonding molecular orbital model of the transition metal coordination environments, we illustrate how the local stability can be enhanced through addition of Ba. In addition, we perform spin-polarized DFT calculations on Ba6Fe25S27 to determine the effect of adopting an antiferromagnetic spin state on its electronic structure. By studying the magnetic properties from an empirical and computational perspective, we hope to elucidate what aspects of the magnetic structure are significant to bonding. PMID- 25140898 TI - Diversity of biological effects induced by longwave UVA rays (UVA1) in reconstructed skin. AB - Despite their preponderance amongst the ultraviolet (UV) range received on Earth, the biological impacts of longwave UVA1 rays (340-400 nm) upon human skin have not been investigated so thoroughly. Nevertheless, recent studies have proven their harmful effects and involvement in carcinogenesis and immunosuppression. In this work, an in vitro reconstructed human skin model was used for exploring the effects of UVA1 at molecular, cellular and tissue levels. A biological impact of UVA1 throughout the whole reconstructed skin structure could be evidenced, from morphology to gene expression analysis. UVA1 induced immediate injuries such as generation of reactive oxygen species and thymine dimers DNA damage, accumulating preferentially in dermal fibroblasts and basal keratinocytes, followed by significant cellular alterations, such as fibroblast apoptosis and lipid peroxidation. The full genome transcriptomic study showed a clear UVA1 molecular signature with the modulation of expression of 461 and 480 genes in epidermal keratinocytes and dermal fibroblasts, respectively (fold change> = 1.5 and adjusted p value<0.001). Functional enrichment analysis using GO, KEGG pathways and bibliographic analysis revealed a real stress with up-regulation of genes encoding heat shock proteins or involved in oxidative stress response. UVA1 also affected a wide panel of pathways and functions including cancer, proliferation, apoptosis and development, extracellular matrix and metabolism of lipids and glucose. Strikingly, one quarter of modulated genes was related to innate immunity: genes involved in inflammation were strongly up-regulated while genes involved in antiviral defense were severely down-regulated. These transcriptomic data were confirmed in dose-response and time course experiments using quantitative PCR and protein quantification. Links between the evidenced UVA1 induced impacts and clinical consequences of UVA1 exposure such as photo-aging, photo-immunosuppression and cancer are discussed. These early molecular events support the contribution of UVA1 to long term harmful consequences of UV exposure and underline the need of an adequate UVA1 photoprotection. PMID- 25140899 TI - Deciphering the glycolipid code of Alzheimer's and Parkinson's amyloid proteins allowed the creation of a universal ganglioside-binding peptide. AB - A broad range of microbial and amyloid proteins interact with cell surface glycolipids which behave as infectivity and/or toxicity cofactors in human pathologies. Here we have deciphered the biochemical code that determines the glycolipid-binding specificity of two major amyloid proteins, Alzheimer's beta amyloid peptide (Abeta) and Parkinson's disease associated protein alpha synuclein. We showed that both proteins interact with selected glycolipids through a common loop-shaped motif exhibiting little sequence homology. This 12 residue domain corresponded to fragments 34-45 of alpha-synuclein and 5-16 of Abeta. By modulating the amino acid sequence of alpha-synuclein at only two positions in which we introduced a pair of histidine residues found in Abeta, we created a chimeric alpha-synuclein/Abeta peptide with extended ganglioside binding properties. This chimeric peptide retained the property of alpha synuclein to recognize GM3, and acquired the capacity to recognize GM1 (an Abeta inherited characteristic). Free histidine (but not tryptophan or asparagine) and Zn2+ (but not Na+) prevented this interaction, confirming the key role of His-13 and His-14 in ganglioside binding. Molecular dynamics studies suggested that the chimeric peptide recognized cholesterol-constrained conformers of GM1, including typical chalice-shaped dimers, that are representative of the condensed cholesterol-ganglioside complexes found in lipid raft domains of the plasma membrane of neural cells. Correspondingly, the peptide had a particular affinity for raft-like membranes containing both GM1 and cholesterol. The chimeric peptide also interacted with several other gangliosides, including major brain gangliosides (GM4, GD1a, GD1b, and GT1b) but not with neutral glycolipids such as GlcCer, LacCer or asialo-GM1. It could inhibit the binding of Abeta1-42 onto neural SH-SY5Y cells and did not induce toxicity in these cells. In conclusion, deciphering the glycolipid code of amyloid proteins allowed us to create a universal ganglioside-binding peptide of only 12-residues with potential therapeutic applications in infectious and neurodegenerative diseases that involve cell surface gangliosides as receptors. PMID- 25140900 TI - Rose Bengal acetate photodynamic therapy (RBAc-PDT) induces exposure and release of Damage-Associated Molecular Patterns (DAMPs) in human HeLa cells. AB - The new concept of Immunogenic Cell Death (ICD), associated with Damage Associated Molecular Patterns (DAMPs) exposure and/or release, is recently becoming very appealing in cancer treatment. In this context, PhotoDynamic Therapy (PDT) can give rise to ICD and to immune response upon dead cells removal. The list of PhotoSensitizers (PSs) able to induce ICD is still short and includes Photofrin, Hypericin, Foscan and 5-ALA. The goal of the present work was to investigate if Rose Bengal Acetate (RBAc), a powerful PS able to trigger apoptosis and autophagy, enables photosensitized HeLa cells to expose and/or release pivotal DAMPs, i.e. ATP, HSP70, HSP90, HMGB1, and calreticulin (CRT), that characterize ICD. We found that apoptotic HeLa cells after RBAc-PDT exposed and released, early after the treatment, high amount of ATP, HSP70, HSP90 and CRT; the latter was distributed on the cell surface as uneven patches and co exposed with ERp57. Conversely, autophagic HeLa cells after RBAc-PDT exposed and released HSP70, HSP90 but not CRT and ATP. Exposure and release of HSP70 and HSP90 were always higher on apoptotic than on autophagic cells. HMGB1 was released concomitantly to secondary necrosis (24 h after RBAc-PDT). Phagocytosis assay suggests that CRT is involved in removal of RBAc-PDT generated apoptotic HeLa cells. Altogether, our data suggest that RBAc has all the prerequisites (i.e. exposure and/or release of ATP, CRT, HSP70 and HSP90), that must be verified in future vaccination experiments, to be considered a good PS candidate to ignite ICD. We also showed tha CRT is involved in the clearance of RBAc photokilled HeLa cells. Interestingly, RBAc-PDT is the first cancer PDT protocol able to induce the translocation of HSP90 and plasma membrane co-exposure of CRT with ERp57. PMID- 25140901 TI - Determination and pharmacokinetic studies of arecoline in dog plasma by liquid chromatography-tandem mass spectrometry. AB - A rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of arecoline concentration in dog plasma. Plasma sample was prepared by protein precipitation using n-hexane (containing 1% isoamyl alcohol) with beta-pinene as an internal standard. Chromatographic separation was achieved on an Agilent C18 column (4.6*75mm, 3.5MUm) using methanol: 5mM ammonium acetate as the mobile phase with isocratic elution. Mass detection was carried out using positive electrospray ionization in multiple reaction monitoring mode. The calibration curve for arecoline was linear over a concentration range of 2-500ng/mL. The intra-day and inter-day accuracy and precision were within the acceptable limits of +/-10% at all concentrations. In summary, the LC-MS/MS method described herein was fully validated and successfully applied to the pharmacokinetic study of arecoline hydrobromide tablets in dogs after oral administration. PMID- 25140902 TI - Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity. AB - Mitochondria contribute to cellular innate immunity against RNA viruses. Mitochondrial-mediated innate immunity is regulated by signalling molecules that are recruited to the mitochondrial membrane, and depends on the mitochondrial inner membrane potential (Deltapsim). Here we examine the physiological relevance of Deltapsim and the mitochondrial-associating influenza A viral protein PB1-F2 in innate immunity. When expressed in host cells, PB1-F2 completely translocates into the mitochondrial inner membrane space via Tom40 channels, and its accumulation accelerates mitochondrial fragmentation due to reduced Deltapsim. By contrast, PB1-F2 variants lacking a C-terminal polypeptide, which is frequently found in low pathogenic subtypes, do not affect mitochondrial function. PB1-F2 mediated attenuation of Deltapsim suppresses the RIG-I signalling pathway and activation of NLRP3 inflammasomes. PB1-F2 translocation into mitochondria strongly correlates with impaired cellular innate immunity, making this translocation event a potential therapeutic target. PMID- 25140903 TI - Stromal luteoma of the ovary: A rare ovarian pathology. PMID- 25140904 TI - Use of multiple data sources and individual case investigation to refine surveillance-based estimates of the HIV care continuum. AB - OBJECTIVES: To assess the HIV care continuum among HIV-infected persons residing in Seattle and King County, WA, at the end of 2011 and compare estimates of viral suppression derived from different population-based data sources. METHODS: We derived estimates for the HIV care continuum using a combination of HIV case and laboratory surveillance data supplemented with individual investigation of cases that seemed to be unlinked to or not retained in HIV care, a jurisdiction-wide population-based retrospective chart review, and local data from the CDC's Medical Monitoring Project and National HIV Behavioral Surveillance. RESULTS: Adjusting for in- and out-migration of persons diagnosed with HIV, laboratory surveillance data supplemented with individual case investigation suggest that 67% of persons diagnosed with HIV and 57% of all HIV-infected persons living in King County at the end of 2011 were virally suppressed (plasma HIV RNA <200 copies/mL). The viral suppression estimates we derived from a population-based chart review and adjusted local Medical Monitoring Project data were similar to the surveillance-derived estimate and identical to each other (59% viral suppression among all HIV-infected persons). CONCLUSIONS: The level of viral suppression in King County is more than twice the national estimate and exceeds estimates of control for other major chronic diseases in the United States. Our findings suggest that national care continuum estimates may be substantially too pessimistic and highlight the need to improve HIV surveillance data. PMID- 25140905 TI - Low-level Viremia early in HIV infection. AB - HIV RNA levels are usually high early in HIV infection. In the HPTN 061 study, men were tested for HIV infection every 6 months; 6 (21.4%) of 28 men who acquired HIV infection during the study had low or undetectable HIV RNA at the time of HIV diagnosis. Antiretroviral drugs were not detected at the time of HIV diagnosis. False-negative HIV test results were obtained for 2 men using multiple assays. Antiretroviral drug resistance mutations were detected in HIV from 1 man. Additional studies are needed to identify factors associated with low HIV RNA levels during early HIV infection. PMID- 25140906 TI - Impact of adherence and anthropometric characteristics on nevirapine pharmacokinetics and exposure among HIV-infected Kenyan children. AB - BACKGROUND: There are insufficient data on pediatric antiretroviral therapy (ART) pharmacokinetics (PK), particularly for children in low- and middle-income countries. METHODS: We conducted a prospective nevirapine (NVP) PK study among HIV-infected Kenyan children aged 3-13 years initiating an NVP-based ART regimen. NVP dose timing was measured through medication event monitors. Participants underwent 2 inpatient assessments: 1 at 4-8 weeks after ART initiation and 1 at 3 4 months after ART initiation. Allometric scaling of oral clearance (CL)/bioavailability (F) and volume of distribution (Vd)/F values were computed. Nonlinear mixed-effects modeling using the first-order conditional estimation with interaction method was performed with covariates. The impact of adherence on time below minimum effective concentration was assessed in the final PK model using medication event monitors data and model-estimated individual parameters. RESULTS: Among 21 children enrolled, mean age was 5.4 years and 57% were female. CL/F was 1.67 L/h and Vd/F was 3.8 L for a median child weighing 15 kg. Participants' age had a significant impact on CL/F (P < 0.05), with an estimated decrease in CL of 6.2% for each 1-year increase in age. Total body water percentage was significantly associated with Vd/F (P < 0.001). No children had >10% of time below minimum effective concentration when the PK model assumed perfect adherence compared with 10 children when adherence data were used. CONCLUSIONS: Age and body composition were significantly associated with children's NVP PK parameters. ART adherence significantly impacted drug exposure over time, revealing subtherapeutic windows that may lead to viral resistance. PMID- 25140907 TI - Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya. AB - BACKGROUND: Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at the time of ART initiation. METHODS: Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (>=1000 copies/mL) at 6 month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic failure were evaluated for drug resistance by consensus and 454-pyrosequencing. RESULTS: Among 386 participants, TDR was detected by OLA in 3.89% (95% confidence interval: 2.19 to 6.33) and was associated with a 10-fold higher rate of virologic failure (hazard ratio: 10.39; 95% confidence interval: 3.23 to 32.41; P < 0.001) compared with those without TDR. OLA detected 24 TDR mutations (K103N: n = 13; Y181C: n = 5; G190A: n = 3; M184V: n = 3) in 15 subjects (NNRTI: n = 15; 3TC: n = 3). Among 51 participants who developed virologic failure, consensus sequencing did not detect additional TDR mutations conferring high-level resistance, and pyrosequencing only detected additional mutations at frequencies <2%. Mutant frequencies <2% at ART initiation were significantly less likely to be found at the time of virologic failure compared with frequencies >=2% (22% vs. 63%; P < 0.001). CONCLUSIONS: Detection of TDR by a point mutation assay may prevent the use of suboptimal ART. PMID- 25140908 TI - Effects of an education and home-based pedometer walking program on ischemic heart disease risk factors in people infected with HIV: a randomized trial. AB - OBJECTIVE: People infected with the human immunodeficiency virus are at an increased risk of developing ischemic heart disease (IHD); however, the effects of an education and home-based pedometer walking program on risk factors of IHD are not known. METHODS: We conducted a 12-month randomized study of an education and home-based pedometer walking program in 84 human immunodeficiency virus infected individuals with risk factors of IHD. RESULTS: Pedometer step count of the control and intervention groups improved significantly (P = 0.03 for both groups) at 6 months but was not significant at 12 months (P = 0.33 and 0.21, respectively). Significant between-group effects were observed in 6-minute walk test distance (P = 0.01), waist to hip ratio (P = 0.00), glucose (P = 0.00), and high-density lipoprotein (P = 0.01) over the 12-month period. The program did not result in change in high-sensitivity C-reactive protein as it was associated with perceived stress (r = 0.23; P = 0.03), weight (r = 0.28; P = 0.01), body mass index (r = 0.35; P < 0.00), waist (r = 0.28; P = 0.01) and hip circumference (r = 0.28; P = 0.01). Multivariate generalized estimation equation analysis demonstrated an inverse association between interaction and perceived stress (logB = -0.01; 95% confidence interval: -0.02 to -0.01; P <0.00) and body mass index (logB = -0.02; 95% confidence interval: -0.03 to -0.002; P = 0.02) at group level. CONCLUSION: An education and home-based pedometer walking program improves physical activity levels, and beneficial changes in other IHD risk factors were noted. PMID- 25140909 TI - GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects. AB - BACKGROUND: GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. METHODS: This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100 400 mg subcutaneous. RESULTS: Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were <=0.1 MUg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from <8% to 28% of corresponding plasma concentrations. CONCLUSIONS: These data suggest 744 LA injection has potential application as a monthly or less frequent HIV treatment or prevention agent. PMID- 25140911 TI - TNF receptors: signaling pathways and contribution to renal dysfunction. AB - Tumor necrosis factor (TNF), initially reported to induce tumor cell apoptosis and cachexia, is now considered a central mediator of a broad range of biological activities from cell proliferation, cell death and differentiation to induction of inflammation and immune modulation. TNF exerts its biological responses via interaction with two cell surface receptors: TNFR1 and TNFR2. (TNFRs). These receptors trigger shared and distinct signaling pathways upon TNF binding, which in turn result in cellular outputs that may promote tissue injury on one hand but may also induce protective, beneficial responses. Yet the role of TNF and its receptors specifically in renal disease is still not well understood. This review describes the expression of the TNFRs, the signaling pathways induced by them and the biological responses of TNF and its receptors in various animal models of renal diseases, and discusses the current outcomes from use of TNF biologics and TNF biomarkers in renal disorders. PMID- 25140913 TI - Endothelin-1, but not angiotensin II, induces afferent arteriolar myosin diphosphorylation as a potential contributor to prolonged vasoconstriction. AB - Bolus administration of endothelin-1 elicits long-lasting renal afferent arteriolar vasoconstriction, in contrast to transient constriction induced by angiotensin II. Vasoconstriction is generally evoked by myosin regulatory light chain (LC20) phosphorylation at Ser19 by myosin light chain kinase (MLCK), which is enhanced by Rho-associated kinase (ROCK)-mediated inhibition of myosin light chain phosphatase (MLCP). LC20 can be diphosphorylated at Ser19 and Thr18, resulting in reduced rates of dephosphorylation and relaxation. Here we tested whether LC20 diphosphorylation contributes to sustained endothelin-1 but not transient angiotensin II-induced vasoconstriction. Endothelin-1 treatment of isolated arterioles elicited a concentration- and time-dependent increase in LC20 diphosphorylation at Thr18 and Ser19. Inhibition of MLCK or ROCK reduced endothelin-1-evoked LC20 mono- and diphosphorylation. Pretreatment with an ETB but not an ETA receptor antagonist abolished LC20 diphosphorylation, and an ETB receptor agonist induced LC20 diphosphorylation. In contrast, angiotensin II caused phosphorylation exclusively at Ser19. Thus, endothelin-1 and angiotensin II induce afferent arteriolar constriction via LC20 phosphorylation at Ser19 due to calcium activation of MLCK and ROCK-mediated inhibition of MLCP. Endothelin-1, but not angiotensin II, induces phosphorylation of LC20 at Thr18. This could contribute to the prolonged vasoconstrictor response to endothelin-1. PMID- 25140912 TI - A systematic review and meta-analysis indicates underreporting of renal dysfunction following endovascular aneurysm repair. AB - Deterioration in renal function has been described after endovascular repair of abdominal aortic aneurysms (EVRs). The etiology is multifactorial and represents an important therapeutic target. A need exists to quantitatively summarize incidence and severity of renal dysfunction after EVR to allow better-informed attempts to preserve renal function and improve life expectancy. Here a systematic search was performed using Medline and Embase for renal function after EVR applying PRISMA statements. Univariate and multivariate random-effects meta analyses were performed to estimate pooled postoperative changes in serum creatinine and creatinine clearance at four time points after EVR. Clinically relevant deterioration in renal function was also estimated at 1 year or more after EVR. Pooled probability of clinically relevant deterioration in renal function at 1 year or more was 18% (95% confidence interval of 14-23%, I2 of 82.5%). Serum creatinine increased after EVR by 0.05 mg/dl at 30 days/1 month, 0.09 mg/dl at 1 month to 1 year, and 0.11 mg/dl at 1 year or more (all significant). Creatinine clearance decreased after EVR by 5.65 ml/min at 1 month 1 year and by 6.58 ml/min at 1 year or more (both significant). Thus, renal dysfunction after EVR is common and merits attention. PMID- 25140914 TI - Single functionalized graphene oxide reconstitutes kinesin mediated intracellular cargo transport and delivers multiple cytoskeleton proteins and therapeutic molecules into the cell. AB - Here, we report a covalently functionalized graphene oxide with Tris-(nitrilo Tris-acetic acid) (TGO), which can reconstitute kinesin mediated intracellular cargo transport, and deliver multiple proteins and therapeutic antimitotic dodecapeptide peptides into the cancer cell. PMID- 25140915 TI - Storable N-phenylcarbamate palladacycles for rapid functionalization of an alkyne encoded protein. AB - Here we report the synthesis of storable N-phenylcarbamate palladacycles that showed robust reactivity in the cross-coupling reaction with an alkyne-encoded protein with a second-order rate constant approaching 19 770 +/- 930 M(-1) s(-1). PMID- 25140916 TI - Synthesis of magnetically separable Ag3PO4/TiO2/Fe3O4 heterostructure with enhanced photocatalytic performance under visible light for photoinactivation of bacteria. AB - Silver orthophosphate (Ag3PO4) is a low-band-gap photocatalyst that has received considerable research interest in recent years. In this work, the magnetic Ag3PO4/TiO2/Fe3O4 heterostructured nanocomposite was synthesized. The nanocomposite was found to exhibit markedly enhanced photocatalytic activity, cycling stability, and long-term durability in the photodegradation of acid orange 7 (AO7) under visible light. Moreover, the antibacterial film prepared from Ag3PO4/TiO2/Fe3O4 nanocomposite presented excellent bactericidal activity and recyclability toward Escherichia coli (E. coli) cells under visible-light irradiation. In addition to the intrinsic cytotoxicity of silver ions, the elevated bactericidal efficiency of Ag3PO4/TiO2/Fe3O4 can be largely attributed to its highly enhanced photocatalytic activity. The photogenerated hydroxyl radicals and superoxide ions on the formed Ag/Ag3PO4/TiO2 interfaces cause considerable morphological changes in the microorganism's cells and lead to the death of the bacteria. PMID- 25140917 TI - Large-scale synthesis of TiO2 microspheres with hierarchical nanostructure for highly efficient photodriven reduction of CO2 to CH4. AB - In this study, a simple and reproducible synthesis strategy was employed to fabricate TiO2 microspheres with hierarchical nanostructure. The microspheres are macroscopic in the bulk particle size (several hundreds to more than 1000 MUm), but they are actually composed of P25 nanoparticles as the building units. Although it is simple in the assembly of P25 nanoparticles, the structure of the as-prepared TiO2 microspheres becomes unique because a hierarchical porosity composed of macropores, larger mesopores (ca. 12.4 nm), and smaller mesopores (ca. 2.3 nm) has been developed. The interconnected macropores and larger mesopores can be utilized as fast paths for mass transport. In addition, this hierarchical nanostructure may also contribute to some extent to the enhanced photocatalytic activity due to increased multilight reflection/scattering. Compared with the state-of-the-art photocatalyst, commercial Degussa P25 TiO2, the as-prepared TiO2 microsphere catalyst has demonstrated significant enhancement in photodriven conversion of CO2 into the end product CH4. Further enhancement in photodriven conversion of CO2 into CH4 can be easily achieved by the incorporation of metals such as Pt. The preliminary experiments with Pt loading reveal that there is still much potential for considerable improvement in TiO2 microsphere based photocatalysts. Most interestingly and significantly, the synthesis strategy is simple and large quantity of TiO2 microspheres (i.e., several hundred grams) can be easily prepared at one time in the lab, which makes large-scale industrial synthesis of TiO2 microspheres feasible and less expensive. PMID- 25140919 TI - The Grief and Meaning Reconstruction Inventory (GMRI): Initial Validation of a New Measure. AB - Although increasing numbers of grief theorists, researchers, and therapists have begun to focus on the quest for meaning in lives disrupted by loss, no convenient and psychometrically validated measure of meanings made specifically in bereavement has been available to guide their efforts. To construct such a measure, the authors began with a systematic content analysis of sense-making, benefit finding, and identity reconstruction themes gleaned from the narrative responses of a sample of 162 adults who were diverse in their age, ethnicity, relationship to the decedent, cause of death, and severity of their grief response. These were then formulated into a set of 65 candidate items in a Likert scale format representing the level of the respondent's endorsement of the item in the past week. Subsequent administration to a second sample of 300 bereaved respondents permitted factor analysis of this pilot version of the Grief and Meaning Reconstruction Inventory (GMRI), and reduced the items to 29, which loaded on 5 distinct factors, labeled Continuing Bonds, Personal Growth, Sense of Peace, Emptiness and Meaninglessness, and Valuing Life. Both the overall GMRI and its constituent factors showed good internal consistency and strong convergent validity in the form of negative correlations with established measures of bereavement-related negative emotions, symptoms of complicated grief, and more general psychological distress and mental health symptomatology, and positive correlations with grief related personal growth. The authors close by noting several specific research and clinical applications of the measure, which could play a useful role in testing and refining contemporary models of meaning made in the wake of loss. PMID- 25140920 TI - Driving forces for the self-assembly of graphene oxide on organic monolayers. AB - Graphene oxide (GO) flakes were self-assembled from solution on surfaces of self assembled monolayers (SAMs), varying in the chemical structure of their head groups. The coverage density of GO relates to strength of attractive interaction, which is largest for Coulomb interaction provided by positively charged SAM head groups and negatively charged GO. A rough surface enhances the coverage density but with the same trend in driving force dependency. The self-assembly approach was used to fabricate field-effect transistors with reduced GO (rGO) as active layer. The SAMs as attractive layer for self-assembly remain almost unaffected by the reduction from GO to rGO and serve as ultra-thin gate dielectrics in devices, which operate at low voltages of maximum 3 V and exhibit a shift of the Dirac voltage related to the dipole moment of the SAMs. PMID- 25140921 TI - Maternal distress in early life predicts the waist-to-hip ratio in schoolchildren. AB - We report on life course stress determinants of overweight in children, using data from the longitudinal follow-up of the nested case-control arm of the SAGE (study of asthma genes and the environment) birth cohort in Manitoba, Canada. Waist and hip measurements were obtained during a clinic visit at age 9-11 years. Multiple linear regression was conducted to determine the relationship between the waist-to-hip ratio and maternal smoking during pregnancy, postpartum maternal distress and stress reactivity in children (cortisol, cortisol-DHEA [dihydroepiandrostrenone] ratio quartiles) following a clinic stressor at age 8 10 years. We found waist-to-hip risk at age 9-11 years to be elevated among boys and girls whose mothers had experienced distress in the postnatal period. This association varied by gender and asthma status. In healthy girls, postpartum distress increased waist-to-hip ratio by a factor of 0.034 (P < 0.01), independent of the child's stage of puberty and adrenarche, cortisol-DHEA ratio and duration of exclusive breastfeeding. Among girls with asthma, maternal smoking during pregnancy was associated with an increased waist-to-hip ratio, if the mother also experienced distress in the postpartum period (0.072, P = 0.038). Among asthmatic boys, an association between maternal distress and waist-to-hip ratio was evident at the highest cortisol-DHEA ratios. Stress-induced changes to leptin and infant over-eating pathways were proposed to explain the postnatal maternal distress effects. Drawing on the theories of evolutionary biology, our findings underscore the significance of postnatal stress in disrupting hypothalamic-pituitary-adrenal axis function in infants and increasing risk for child overweight. PMID- 25140922 TI - Pregnancy and neonatal outcomes following hyperemesis gravidarum. AB - Undernutrition during pregnancy is associated with detrimental pregnancy and neonatal outcomes, which can have long-term implications for the infant. Hyperemesis gravidarum may severely limit nutritional intake. The aim of this study was to investigate the effect of hyperemesis on pregnancy and neonatal outcome, particularly gestation length and infant size at birth. Seventy-five prospectively recruited women admitted to a tertiary level hospital in Auckland, with hyperemesis gravidarum between March 2003 and October 2005, were compared to 142 controls matched for age, parity, ethnicity and expected date of delivery. Data were obtained from electronic records and analysed by Student's t-test, chi2, Wilcoxon, Fisher's exact tests and linear regression. Length of gestation, birth weight and crown-heel length were not different between participants and controls. Infants born to women with hyperemesis gravidarum had smaller head circumferences (Z-score mean (s.d.) 0.02 (0.16) v. 0.43 (0.11), P = 0.04 in all infants and -0.02 (1.24) v. 0.48 (1.29), P = 0.01 in-term infants). This study found hyperemesis gravidarum to be associated with smaller head circumferences in offspring. Given the reported associations between smaller head circumference at birth and lower cognitive ability and higher risk of cardiovascular disease in later life, further study is necessary to confirm these results and to determine whether there are any long-term implications for the offspring. PMID- 25140923 TI - Cord blood immune biomarkers in small for gestational age births. AB - Fetal growth restriction is a risk factor for development of adulthood diseases, but the biological mechanism of this association remains unknown. Limited biomarkers have been studied in settings of preterm birth and maternal inflammation, but the relationship between a wide range of immune biomarkers and fetal growth has not been studied. The hypothesis of this study was that fetal growth restriction is associated with altered immune biomarker levels. We examined the relationship between small for gestational age (SGA) status and 27 umbilical cord blood immune biomarkers. This study was part of a large-scale cohort study of preterm birth and low birth weight conducted at Boston Medical Center, an inner city, predominantly minority patient population. Growth status was determined based on birth weight standardized to an internal reference. There were 74 SGA births and 319 appropriate for age (AGA) births with complete clinical and biomarker data. Adjusting for covariates and using AGA as reference, SGA births had lower levels of log IL-1beta (ng/l; beta -0.38, 95% CI -0.57, 0.19, P < 0.01), log BDNF (beta -0.29, 95% CI -0.55, -0.03, P < 0.05) and log NT 3 (beta -0.46, 95% CI -0.77, -0.15, P < 0.01). No associations were found between other biomarkers and SGA. In conclusion, three biomarkers were selectively associated with SGA status. Our results provide information that could be used to guide additional studied aimed at determining mechanisms that contribute to fetal growth. PMID- 25140924 TI - Pre- and postnatal determinants of childhood body size: cohort and sibling analyses. AB - Growing evidence suggests obesity may have its roots in early life but it is still uncertain whether prenatal factors operate primarily though altering early infant growth. It is also still unclear if rapid growth during selected time periods is more important than other time periods in predicting future body size. Using prospectively collected data on 20,523 participants born from 1959 to 1966 (10,327 boys; 10,196 girls) of the Collaborative Perinatal Project, we investigated the associations between pre- and postnatal factors and childhood body size at age 7 years and compared these associations across linear, logistic and quantile regression models. Maternal body mass index (BMI), maternal pregnancy weight gain, birth weight and postnatal weight change for three time periods (birth to 4 months; 4-12 months; 1-4 years) were all positively and independently associated with BMI at age 7 years. Rapid growth during each time period had a similar association BMI at age 7 years. For example, a 10-percentile increase in weight increased the probability of being overweight at age 7 years by approximately two-fold regardless of time period (OR = 1.8-2.2 for boys and girls). Using same-sex siblings (n = 571 boy sets; n = 651 girl sets) from the same cohort, we observed that siblings with higher BMI at age 7 years than their same-sex siblings were more likely to have higher maternal pregnancy weight gain, higher maternal pre-pregnancy BMI, higher birth weight and increased rate of weight gain during the three time periods. These consistent findings both from the overall cohort and the sibling analyses suggest that there are multiple, rather than specific critical periods of influence shaping childhood body size. PMID- 25140925 TI - Perinatal programming of murine immune responses by polyunsaturated fatty acids. AB - Linoleic acid and alpha-linolenic acid are essential fatty acids (eFAs) and have to be acquired from the diet. eFAs are the precursors for long-chain polyunsaturated fatty acids (lcPUFAs), which are important immune-modulating compounds. lcPUFAs can be converted into eicosanoids and other mediators. They affect membrane structure and fluidity and can alter gene expression. There has been a marked change in dietary fatty acid intake over the last several decades. Since eFAs are acquired from the diet and immune development occurs mainly perinatally, the maternal diet may influence fetal and neonatal eFA levels, and thereby lcPUFA status, and thus immune development and function. To study whether early exposure to eFAs can program immune function, mice were fed diets varying in the ratio of omega-3 to omega-6-eFAs during pregnancy and/or lactation. After weaning, pups received a Western-style diet. At 11 weeks of age, the effects of maternal diet on the offspring's allergic and vaccination responses were examined using the T-helper 2 driven ovalbumin-induced allergy model and the T-helper 1 driven influenza-vaccination model, respectively. Offspring of dams fed a high alpha-linolenic acid diet during lactation showed an enhanced vaccination response. As diets with either low or high omega-3/omega-6-eFA ratio attenuated the T-helper 2 allergic response, the high alpha-linolenic acid diet fed during lactation had the most pronounced effect. These results indicate that there is a programming effect of maternal diet on the offspring's immune response and that in mice the window of greatest susceptibility to maternal dietary intervention is the lactation/suckling period. PMID- 25140926 TI - Maternal malnutrition and placental insufficiency induce global downregulation of gene expression in fetal kidneys. AB - Malnutrition during pregnancy causes intrauterine growth restriction and long term changes in the offspring's physiology and metabolism. To explore molecular mechanisms by which the intrauterine environment conveys programming in fetal kidneys, an organ known to undergo substantial changes in many animal models of late gestational undernutrition, we used a microswine model of maternal protein restriction (MPR) in which sows were exposed to isocaloric low protein (LP) diet during late gestation/early lactation to encompass the bulk of nephrogenesis. To define general v. model-specific effects, we also used a sheep model of placental insufficiency. In kidneys from near-term fetal and neonatal microswine LP offspring, per cell levels of total RNA, poly(A)+ mRNA and transcripts of several randomly chosen housekeeping genes were significantly reduced compared to controls. Microarray analysis revealed only a few MPR-resistant genes that escape such downregulation. The ratio of histone modifications H3K4m3/H3K9m3 (active/silenced) was reduced at promoters of downregulated but not MPR-resistant genes suggesting that transcriptional suppression is the point of control. In juvenile offspring, on a normal diet from weaning, cellular RNA levels and histone mark patterns were recovered to near control levels, indicating that global repression of transcription is dependent on ongoing MPR. Importantly, cellular RNA content was also reduced in ovine fetal kidneys during placental insufficiency. These studies show that global repression of transcription may be a universal consequence of a poor intrauterine environment that contributes to fetal restriction. PMID- 25140927 TI - Attitudes towards microbicide use for bacterial vaginosis in pregnancy. AB - Background Bacterial vaginosis (BV) is the most common reproductive tract infection (RTI) and is a significant risk factor for preterm birth. Microbicides could be an option for the prevention and treatment of BV in pregnancy, and understanding use of the product will be crucial. The present study explored attitudes of women in the third trimester of pregnancy regarding topical microbicide use for the prevention and treatment of BV. METHODS: Twenty-six women in their third trimester were interviewed regarding their knowledge and beliefs about RTIs during pregnancy and attitudes concerning the use of topical microbicides for prevention and treatment of BV. RESULTS: Participants had a mean age of 24.9 years, were largely under-represented minorities and the majority had had past pregnancies. Participants had knowledge and experience with RTIs but not BV. They were open to the use of microbicides for prevention or treatment of BV, but believed that women requiring treatment would be more motivated. Rationales for acceptability were most commonly related to the baby's health. Practical issues that may interfere with use were often, but not always, related to pregnancy. There was a range of attitudes about partner involvement in decision making and the practicalities of product use. CONCLUSION: Pregnant women are knowledgeable about RTIs but not necessarily BV. The women in this study found microbicide use acceptable, particularly for treatment. To improve acceptability and use, education would be needed about BV and possible complications, how to overcome practical problems and the value of involving partners in the decision. PMID- 25140928 TI - Discussion of the influence of CO and CH4 in CO2 transport, injection, and storage for CCS technology. AB - This paper discusses the influence of the noncondensable impurities CO and CH4 on Carbon Capture and Storage (CCS) technology. We calculated and drew conclusions about the impact of both impurities in the CO2 on selected transport, injection, and storage parameters (pipeline pressure drop, storage capacity, etc.), whose analysis is necessary for the safe construction and operation of CO2 pipelines and for the secure long-term geological storage of anthropogenic CO2. To calculate these parameters, it is necessary to acquire data on the volumetric properties and the vapor-liquid equilibrium of the fluid being subjected to CCS. In addition to literature data, we used new experimental data, which are presented here and were obtained for five mixtures of CO2+CO with compositions characteristic of the typical emissions of the E.U. and the U.S.A. Temperatures and pressures are based on relevant CO2 pipeline and geological storage site values. From our experimental results, Peng-Robinson, PC-SAFT, and GERG Equations of State for were validated CO2+CO under the conditions of CCS. We conclude that the concentration of both impurities strongly affects the studied parameters, with CO being the most influential and problematic. The overall result of these negative effects is an increase in the difficulties, risks, and overall costs of CCS. PMID- 25140929 TI - Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine. AB - Vaccines used against seasonal influenza are poorly effective against influenza A viruses of novel subtypes that may have pandemic potential. Furthermore, pre(pandemic) influenza vaccines are poorly immunogenic, which can be overcome by the use of adjuvants. A limited number of adjuvants has been approved for use in humans, however there is a need for alternative safe and effective adjuvants that can enhance the immunogenicity of influenza vaccines and that promote the induction of broad-protective T cell responses. Here we evaluated a novel nanoparticle, G3, as an adjuvant for a seasonal trivalent inactivated influenza vaccine in a mouse model. The G3 adjuvant was formulated with or without steviol glycosides (DT, for diterpenoid). The use of both formulations enhanced the virus specific antibody response to all three vaccine strains considerably. The adjuvants were well tolerated without any signs of discomfort. To assess the protective potential of the vaccine-induced immune responses, an antigenically distinct influenza virus strain, A/Puerto Rico/8/34 (A/PR/8/34), was used for challenge infection. The vaccine-induced antibodies did not cross-react with strain A/PR/8/34 in HI and VN assays. However, mice immunized with the G3/DT adjuvanted vaccine were partially protected against A/PR/8/34 infection, which correlated with the induction of anamnestic virus-specific CD8(+) T cell responses that were not observed with the use of G3 without DT. Both formulations induced maturation of human dendritic cells and promoted antigen presentation to a similar extent. In conclusion, G3/DT is a promising adjuvant formulation that not only potentiates the antibody response induced by influenza vaccines, but also induces T cell immunity which could afford broader protection against antigenically distinct influenza viruses. PMID- 25140930 TI - Humoral responses to independent vaccinations are correlated in healthy boosted adults. AB - BACKGROUND: Roughly half of U.S. adults do not receive recommended booster vaccinations, but protective antibody levels are rarely measured in adults. Demographic factors, vaccination history, and responses to other vaccinations could help identify at-risk individuals. We sought to characterize rates of seroconversion and determine associations of humoral responses to multiple vaccinations in healthy adults. METHODS: Humoral responses toward measles, mumps, tetanus toxoid, pertussis, hepatitis B surface antigen, and anthrax protective antigen were measured by ELISA in post-immunization samples from 1465 healthy U.S. military members. We examined the effects of demographic and clinical factors on immunization responses, as well as assessed correlations between vaccination responses. RESULTS: Subsets of boosted adults did not have seroprotective levels of antibodies toward measles (10.4%), mumps (9.4%), pertussis (4.7%), hepatitis B (8.6%) or protective antigen (14.4%) detected. Half lives of antibody responses were generally long (>30 years). Measles and mumps antibody levels were correlated (r=0.31, p<0.001), but not associated with select demographic features or vaccination history. Measles and mumps antibody levels also correlated with tetanus antibody response (r=0.11, p<0.001). CONCLUSIONS: Vaccination responses are predominantly robust and vaccine specific. However, a small but significant portion of the vaccinated adult population may not have quantitative seroprotective antibody to common vaccine-preventable infections. PMID- 25140931 TI - Bilateral high- and low-frequency rTMS in acute stroke patients with hemiparesis: a comparative study with unilateral high-frequency rTMS. AB - BACKGROUND: High- and low-frequency repetitive transcranial magnetic stimulation (HF-rTMS and LF-rTMS) has been shown to be beneficial for upper limb hemiparesis in patients with acute stroke. However, no study has examined the usefulness of bilateral application of HF- and LF-rTMS (BL-rTMS). METHODS: Fifty-eight hemiparetic patients with acute stroke were randomly assigned into two groups: HF rTMS group and BL-rTMS group. All patients were scheduled to receive five sessions of either HF-rTMS over the lesional hemisphere or BL-rTMS over both hemispheres for 5 days. Motor function of the affected upper limb was evaluated using the Brunnstrom Recovery Stage (BRS) for upper-limb and hand-fingers, grip strength and tapping frequency, before the first session and after the last session of rTMS. RESULTS: Improvement of BRS for the upper limb and hand/finger was significantly greater in the BL-rTMS group than the HF-rTMS group (p < 0.01). Improvement in grip strength and tapping frequency was also greater in the BL rTMS group, although the differences were not statistically significant. CONCLUSIONS: The proposed BL-rTMS is safe and feasible and showed a greater improvement of BRS of the affected upper limb compared to HF-rTMS. This novel rTMS approach may be a useful intervention for hemiparetic patients with acute stroke. PMID- 25140932 TI - Physician-assisted suicide: a matter of choice. PMID- 25140934 TI - Finding the courage to seek care. PMID- 25140935 TI - ID badges: what's really in a name? PMID- 25140936 TI - A tale of two hospital systems: preparing new graduates for clinical practice. PMID- 25140937 TI - Introducing nursing informatics. PMID- 25140938 TI - Spotlight on nurse researcher Kimberly Stephens. PMID- 25140942 TI - Patient education. Angina. PMID- 25140943 TI - Learning self-advocacy. PMID- 25140944 TI - How clinical nurse leaders can improve rural healthcare. PMID- 25140945 TI - Intracolonic administration of vancomycin for Clostridium difficile infection. PMID- 25140946 TI - Professional perspectives on planned home births. PMID- 25140947 TI - Make carbohydrate counting add up. PMID- 25140949 TI - Fighting bed alarm fatigue in orthopedic units. PMID- 25140950 TI - Ebola virus disease: an emerging threat. PMID- 25140952 TI - FDA approval of bedaquiline--the benefit-risk balance for drug-resistant tuberculosis. PMID- 25140953 TI - Did hospital engagement networks actually improve care? PMID- 25140954 TI - The impact and evolution of Medicare Part D. PMID- 25140955 TI - The challenges of challenge experiments. PMID- 25140956 TI - Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. AB - BACKGROUND: Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care. METHODS: In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct. RESULTS: A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04). CONCLUSIONS: Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.). PMID- 25140957 TI - Oral GS-5806 activity in a respiratory syncytial virus challenge study. AB - BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of infant hospitalizations and is increasingly recognized as a cause of considerable morbidity and mortality. No accepted antiviral treatment exists. METHODS: We conducted a double-blind, placebo-controlled study of GS-5806, an oral RSV-entry inhibitor, in healthy adults who received a clinical challenge strain of RSV intranasally. Participants were monitored for 12 days. At the time of a positive test for RSV infection or 5 days after inoculation, whichever occurred first, participants were randomly assigned to receive GS-5806 or placebo in one of seven sequential cohorts. Cohorts 1 to 4 received a first dose of 50 mg of GS-5806 and then 25 mg daily for the next 4 days, cohort 5 received a first dose of 50 mg and then 25 mg daily for the next 2 days, cohort 6 received one 100-mg dose, and cohort 7 received a first dose of 10 mg and then 5 mg daily for the next 4 days. Dose selection for cohorts 5, 6, and 7 occurred after an interim analysis of data for cohorts 1 to 4. The primary end point was the area under the curve (AUC) for the viral load, which was assessed after administration of the first dose through the 12th day after inoculation. Secondary end points were mucus weight and symptom scores. RESULTS: Among the 54 participants in cohorts 1 to 4 who were infected with RSV, active treatment was associated with a lower viral load (adjusted mean, 250.7 vs. 757.7 log10 plaque-forming-unit equivalents [PFUe] * hours per milliliter; P<0.001), lower total mucus weight (mean, 6.9 g vs. 15.1 g; P=0.03), and a lower AUC for the change from baseline in symptom scores (adjusted mean, -20.2 vs. 204.9 * hours; P=0.005). The results were similar in cohorts 5, 6, and 7. Adverse events, including low neutrophil counts and increased levels of alanine aminotransferase, were more common among participants receiving GS-5806. CONCLUSIONS: Treatment with GS-5806 reduced the viral load and the severity of clinical disease in a challenge study of healthy adults. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01756482.). PMID- 25140958 TI - Multidrug-resistant tuberculosis and culture conversion with bedaquiline. AB - BACKGROUND: Bedaquiline (Sirturo, TMC207), a diarylquinoline that inhibits mycobacterial ATP synthase, has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis, when added to a preferred background regimen for 8 weeks. METHODS: In this phase 2b trial, we randomly assigned 160 patients with newly diagnosed, smear-positive, multidrug resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks, followed by 200 mg three times a week for 22 weeks, or placebo, both in combination with a preferred background regimen. The primary efficacy end point was the time to sputum-culture conversion in liquid broth. Patients were followed for 120 weeks from baseline. RESULTS: Bedaquiline reduced the median time to culture conversion, as compared with placebo, from 125 days to 83 days (hazard ratio in the bedaquiline group, 2.44; 95% confidence interval, 1.57 to 3.80; P<0.001 by Cox regression analysis) and increased the rate of culture conversion at 24 weeks (79% vs. 58%, P=0.008) and at 120 weeks (62% vs. 44%, P=0.04). On the basis of World Health Organization outcome definitions for multidrug-resistant tuberculosis, cure rates at 120 weeks were 58% in the bedaquiline group and 32% in the placebo group (P=0.003). The overall incidence of adverse events was similar in the two groups. There were 10 deaths in the bedaquiline group and 2 in the placebo group, with no causal pattern evident. CONCLUSIONS: The addition of bedaquiline to a preferred background regimen for 24 weeks resulted in faster culture conversion and significantly more culture conversions at 120 weeks, as compared with placebo. There were more deaths in the bedaquiline group than in the placebo group. (Funded by Janssen Pharmaceuticals; TMC207-C208 ClinicalTrials.gov number, NCT00449644.). PMID- 25140959 TI - Somatic mutations in cerebral cortical malformations. AB - BACKGROUND: Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. METHODS: Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, >=200*) to leukocyte-derived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing. RESULTS: Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. CONCLUSIONS: Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. (Funded by the National Institute of Neurological Disorders and Stroke and others.). PMID- 25140960 TI - Aortic-valve stenosis--from patients at risk to severe valve obstruction. PMID- 25140961 TI - Cancer of unknown primary site. PMID- 25140962 TI - Images in clinical medicine. Intraoral presentation of antrochoanal polyp. PMID- 25140963 TI - Case records of the Massachusetts General Hospital. Case 26-2014. A 21-month-old boy with lethargy, respiratory distress, and abdominal distention. PMID- 25140964 TI - More blood for sickle cell anemia? PMID- 25140965 TI - Progress in the prevention and treatment of RSV infection. PMID- 25140966 TI - Molecular basis of giant cells in tuberous sclerosis complex. PMID- 25140967 TI - Treatments for idiopathic pulmonary fibrosis. PMID- 25140968 TI - Treatments for idiopathic pulmonary fibrosis. PMID- 25140969 TI - Treatments for idiopathic pulmonary fibrosis. PMID- 25140970 TI - Treatments for idiopathic pulmonary fibrosis. PMID- 25140971 TI - Treatments for idiopathic pulmonary fibrosis. PMID- 25140972 TI - The metabolic syndrome and DYRK1B. PMID- 25140973 TI - The metabolic syndrome and DYRK1B. PMID- 25140974 TI - The metabolic syndrome and DYRK1B. PMID- 25140975 TI - The metabolic syndrome and DYRK1B. PMID- 25140976 TI - Images in clinical medicine. Posterior mediastinal mass. PMID- 25140977 TI - Interactive medical case. A man with fever, cough, and rash. PMID- 25140978 TI - Prevalence and characterization of antimicrobial-resistant Escherichia coli isolated from conventional and organic vegetables. AB - To compare the characteristics and to identify the epidemiological relationships of Escherichia coli isolated from organic and conventional vegetables, the antimicrobial resistance and genetic properties of E. coli were investigated from 2010 to 2011. E. coli was isolated from 1 of 111 (0.9%) organic vegetables and from 20 of 225 (8.9%) conventional vegetables. The majority of strains were isolated from the surrounding farming environment (n=27/150 vs. 49/97 in organic vs. conventional samples). The majority of the vegetable strains were isolated from the surrounding farming environments. E. coli isolated from organic vegetables showed very low antimicrobial resistance rates except for cephalothin, ranging from 0% to 17.9%, while the resistance rates to cephalothin (71%) were extremely high in both groups. E. coli isolates expressed various resistance genes, which most commonly included blaTEM, tet(A), strA, strB, and qnrS. However, none of the isolates harbored tet(D), tet(E), tet(K), tet(L), tet(M), or qnrA. The transferability of tet gene, tet(A), and tet(B) was identified in tetracycline-resistant E. coli, and the genetic relationship was confirmed in a few cases from different sources. With regard to the lower antimicrobial resistance found in organic produce, this production mode seems able to considerably reduce the selection of antimicrobial-resistant bacteria on vegetables. PMID- 25140979 TI - Spontaneous abortion and functional polymorphism (Val16Ala) in the manganese SOD gene. AB - Spontaneous abortion is the most common complication of early pregnancy. Genetic factors have been hypothesised to play a role in spontaneous abortion. Since it is possible that the balance of oxidants and antioxidants can be affected by different genetic variants, gene polymorphisms have been proposed as a susceptibility factor that increases the chance of miscarriage. Manganese superoxide dismutase is an important antioxidant enzyme encoded by manganese superoxide dismutase (MnSOD) gene. The aim of this experiment was to assess whether Val16Ala polymorphism of MnSOD gene is associated with miscarriage in northern Iran. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping. Statistical analyses were conducted using the chi(2)-test. The genetic distributions did not differ significantly between cases and controls, however slightly more Val/Val genotypes were found among the patients compared with control subjects (p = 0.059). No correlation was observed between susceptibility to abortion and MnSOD Val16Ala polymorphism. Larger population-based studies are needed for clarifying the relationship between abortion and MnSOD genotypes. PMID- 25140980 TI - Motivational interviewing for alcohol misuse in young adults. AB - BACKGROUND: Globally, harmful use of alcohol results in approximately 2.5 million deaths each year. About 9% of these deaths are young people between the ages of 15 and 29 years (WHO 2011), mainly resulting from motor vehicle accidents, homicides, suicides and drownings. Hazardous drinking levels for men (consuming over 40 g/day alcohol on average, that is 5 units) double the risk of liver disease, raised blood pressure, some cancers and violent death (because some people who have this average alcohol consumption drink heavily on some days). For women, over 24 g/day average alcohol consumption (3 units) increases the risk for developing liver disease and breast cancer. Motivational interviewing (MI) is a popular technique for addressing excessive drinking in young adults but its effectiveness has not previously been examined in a Cochrane review. OBJECTIVES: The specific objectives were:(1) to summarise current evidence about the effects of MI intended to address alcohol and alcohol-related problems in young adults, compared with no intervention or a different intervention, on alcohol consumption and other substantive outcome measures;(2) to investigate whether the effects of MI are modified by the length of the intervention. SEARCH METHODS: Relevant evidence was identified from (1) Cochrane Central Register of Controlled Trials (CENTRAL) (October 2013), (2) MEDLINE (January 1966 to October 2013), (3) EMBASE (January 1988 to October 2013), and (4) PsycINFO (1985 to October 2013). References of topic-related systematic reviews and the included studies were handsearched. SELECTION CRITERIA: Randomised controlled trials and cluster randomised controlled trials of young people up to the age of 25 years in college and non-college settings comparing MIs with no intervention or a different intervention for prevention of alcohol misuse and alcohol-related problems were included. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: A total of 66 randomised trials (17,901 participants) were included four of which were cluster randomised. Studies with longer-term follow-up (four plus months) were of more interest when considering the sustainability of intervention effects.At four or more months follow-up, effects were found for the quantity of alcohol consumed (standardised mean difference (SMD) -0.14; 95% confidence interval (CI) -0.20 to 0.08 or a reduction from 13.7 drinks/week to 12.2 drinks/week), moderate quality of evidence; frequency of alcohol consumption (SMD -0.11; 95% CI -0.19 to -0.03 or a reduction in the number of days/week alcohol was consumed from 2.74 days to 2.57 days), moderate quality of evidence; and peak blood alcohol concentration (BAC) (SMD -0.14; 95% CI -0.23 to -0.05 or a decrease in peak BAC from 0.144% to 0.129%), moderate quality of evidence. A marginal effect was found for alcohol problems (SMD -0.08; 95% CI -0.15 to 0.00 or a reduction in an alcohol problems scale score from 8.91 to 8.18), low quality of evidence. No effects were found for binge drinking (SMD -0.05; 95% CI -0.12 to 0.01), moderate quality of evidence; or average BAC (SMD -0.08; 95% CI -0.22 to 0.06), moderate quality of evidence. We also considered other outcomes and at four or more months follow-up we found no effects on drink-driving (SMD -0.11; 95% CI -0.31 to 0.09), moderate quality of evidence; or other alcohol-related risky behaviour (SMD -0.14; 95% CI 0.30 to 0.02), moderate quality of evidence.Further analyses showed that the type of control comparison (assessment only versus alternative intervention) did not predict the outcome in a clear or straightforward way; and there was no consistent relationship between the duration of the MI intervention (in minutes) and effect size. AUTHORS' CONCLUSIONS: The results of this review indicate that there are no substantive, meaningful benefits of MI interventions for the prevention of alcohol misuse. Although some significant effects were found, we interpret the effect sizes as being too small, given the measurement scales used in the studies included in the review, to be of relevance to policy or practice. Moreover, the statistically significant effects are not consistent for all misuse measures, heterogeneity was a problem in some analyses and bias cannot be discounted as a potential cause of these findings. PMID- 25140981 TI - An empirical study of alcohol consumption by patients considering HCV treatment. AB - BACKGROUND: Alcohol accelerates the course of hepatitis C (HCV) infection and liver damage. Little is known about recency of alcohol use among patients with HCV. OBJECTIVES: Alcohol consumption recency was compared among HCV patients with and without alcohol use disorders and current and lifetime alcohol use histories. METHODS: Patients considering antiviral treatment for HCV (n = 309) recruited from university-affiliated and VA liver and infectious disease clinics were assessed for lifetime and current-year psychiatric disorders and alcohol-use patterns. Full diagnostic interviews, self-report surveys, medical record review, and urine screening for recent alcohol and drug use were conducted. RESULTS: 60% used alcohol in the last year. Besides alcohol history, those who stopped using alcohol in the past year differed from those with no lifetime use only in gender (60% vs. 22%); however, patients no longer using alcohol in the last year were less likely than those still using to have a current drug use disorder (16% vs. 3%) or last-month drug use (52% vs. 30%), and had fewer current risky behaviors (1.3 vs. 0.6). Among patients with last-year alcohol use, those with past alcohol use disorders differed from those without only by higher prevalence of drug use disorder (84% vs. 47%) and drug use after HCV diagnosis (67% vs. 43%). CONCLUSIONS: Patients who had stopped using alcohol for at least a year were much like those who never used alcohol in regard to other drug use, psychiatric history, smoking, and risky behaviors. These findings indicate that HCV patients with at least a year of abstinence from alcohol, including those with a history of alcohol use disorder, should be considered HCV treatment candidates. PMID- 25140982 TI - Orthopedic surgery in ancient Egypt. AB - BACKGROUND: Ancient Egypt might be considered the cradle of medicine. The modern literature is, however, sometimes rather too enthusiastic regarding the procedures that are attributed an Egyptian origin. I briefly present and analyze the claims regarding orthopedic surgery in Egypt, what was actually done by the Egyptians, and what may have been incorrectly ascribed to them. METHODS: I reviewed the original sources and also the modern literature regarding surgery in ancient Egypt, concentrating especially on orthopedic surgery. RESULTS: As is well known, both literary sources and the archaeological/osteological material bear witness to treatment of various fractures. The Egyptian painting, often claimed to depict the reduction of a dislocated shoulder according to Kocher's method, is, however, open to interpretation. Therapeutic amputations are never depicted or mentioned in the literary sources, while the specimens suggested to demonstrate such amputations are not convincing. INTERPRETATION: The ancient Egyptians certainly treated fractures of various kinds, and with varying degrees of success. Concerning the reductions of dislocated joints and therapeutic amputations, there is no clear evidence for the existence of such procedures. It would, however, be surprising if dislocations were not treated, even though they have not left traces in the surviving sources. Concerning amputations, the general level of Egyptian surgery makes it unlikely that limb amputations were done, even if they may possibly have been performed under extraordinary circumstances. PMID- 25140983 TI - Osteoarthritis treatment using autologous conditioned serum after placebo. AB - BACKGROUND AND PURPOSE: Autologous conditioned serum (ACS) is a disease-modifying drug for treatment of knee osteoarthritis, and modest superiority over placebo was reported in an earlier randomized controlled trial (RCT). We hypothesized that when given the opportunity, placebo-treated patients from that RCT would now opt for ACS treatment, which would result in a greater clinical improvement than placebo. METHODS: Of 74 patients treated with placebo in the previous trial, 20 opted for ACS treatment. Patients who did not choose further treatment were interviewed about their reasons. Clinical improvement of the 20 ACS-treated patients was measured using knee-specific clinical scores, as was "response shift" at 3 and 12 months. RESULTS: In the 20 patients who did opt for ACS, the visual analog scale (VAS) score for pain improved; but after 12 months, clinical results were similar to those after placebo treatment. Response shift measurement demonstrated that the 20 patients had adapted to their disabilities during treatment. INTERPRETATION: Placebo-treated patients from an earlier trial were reluctant to undergo ACS treatment, in part due to the laborious nature of the therapy. In a subset of patients who opted for treatment, ACS treatment after placebo did not result in greater clinical improvement than placebo treatment only. However, due to the limited power of the current study and possible selection bias, definite advice on using or refraining from ACS cannot be given. PMID- 25140984 TI - Computer-assisted surgery in orthopedic oncology. AB - BACKGROUND AND PURPOSE: In orthopedic oncology, computer-assisted surgery (CAS) can be considered an alternative to fluoroscopy and direct measurement for orientation, planning, and margin control. However, only small case series reporting specific applications have been published. We therefore describe possible applications of CAS and report preliminary results in 130 procedures. PATIENTS AND METHODS: We conducted a retrospective cohort study of all oncological CAS procedures in a single institution from November 2006 to March 2013. Mean follow-up time was 32 months. We categorized and analyzed 130 procedures for clinical parameters. The categories were image-based intralesional treatment, image-based resection, image-based resection and reconstruction, and imageless resection and reconstruction. RESULTS: Application to intralesional treatment showed 1 inadequate curettage and 1 (other) recurrence in 63 cases. Image-based resections in 42 cases showed 40 R0 margins; 16 in 17 pelvic resections. Image-based reconstruction facilitated graft creation with a mean reconstruction accuracy of 0.9 mm in one case. Imageless CAS was helpful in resection planning and length- and joint line reconstruction for tumor prostheses. INTERPRETATION: CAS is a promising new development. Preliminary results show a high number of R0 resections and low short-term recurrence rates for curettage. PMID- 25140985 TI - Metallosis and elevated serum levels of tantalum following failed revision hip arthroplasty--a case report. PMID- 25140986 TI - Wear of a sequentially annealed polyethylene acetabular liner. AB - BACKGROUND AND PURPOSE: We previously reported on a randomized controlled trial (RCT) that examined the effect of adding tobramycin to bone cement after femoral stem migration. The present study examined femoral head penetration into both conventional and highly crosslinked polyethylene acetabular liners in the same group of RCT patients, with a minimum of 5 years of postoperative follow-up. PATIENTS AND METHODS: Linear penetration of the femoral head into an X3 (Stryker) crosslinked polyethylene (XLPE) liner was measured in 18 patients (19 hips) using radiostereometric analysis (RSA). Femoral head penetration was also measured in 6 patients (6 hips) with a conventional polyethylene liner (CPE), which served as a control group. RESULTS: The median proximal femoral head penetration in the XLPE group after 5.5 years was 0.025 mm with a steady-state penetration rate of 0.001 mm/year between year 1 and year 5. The CPE liner showed a median proximal head penetration of 0.274 mm after 7.2 years, at a rate of 0.037 mm/year. INTERPRETATION: The Trident X3 sequentially annealed XLPE liner shows excellent in vivo wear resistance compared to non-crosslinked CPE liners at medium-term implantation. The rate of linear head penetration in the XLPE liners after > 5 years of follow-up was 0.001 mm/year, which is in close agreement with the results of previous studies. PMID- 25140987 TI - Sequence of the Essex-Lopresti lesion--a high-speed video documentation and kinematic analysis. PMID- 25140988 TI - A biochemical study of the distribution of collagen and its crosslinks in knee ligaments and the patellar tendon. AB - PURPOSE: The purpose of this study was to investigate biochemical differences in collagen crosslinks from different locations within the ligaments and a tendon of the human knee. MATERIALS AND METHODS: The anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), lateral collateral ligament (LCL), and patellar tendon (PT) were obtained from 24 cadavers (13 men and 11 women) whose average age at the time of death was 84.8 years. Ligaments and PT samples were obtained from the femoral and tibial insertions and the midsubstance. Hydroxyproline (Hyp) and collagen crosslinks, including pyridinoline (Pyr) and pentosidine (Pen), were compared among the different sites. RESULTS: The midsubstance Hyp concentration was greater than at the femoral and tibial insertions in the ACL (p = 0.00124 and 0.000255, respectively) and PCL (p = 0.00036 and 0.042, respectively). The Pyr:collagen ratio did not differ among sites in any of the ligaments or PT. The Pen:collagen ratio at the midsubstance was greater than at the femoral and tibial insertions in the ACL (p = 0.00022 and 0.00025, respectively) and LCL (p = 0.000081 and 0.000021, respectively) and was greater at the femoral insertion in the MCL (p = 0.00010). CONCLUSIONS: The mature collagen crosslink Pyr was not different in distribution in knee ligaments and the PT. Pen increased at the midsubstance ligaments and the PT. As increased Pen may represent ligament degeneration, this may indicate that degeneration may progress more rapidly at the midsubstance than at the insertion sites of a ligament. PMID- 25140989 TI - Biomaterial-mesenchymal stem cell constructs for immunomodulation in composite tissue engineering. AB - Cell-based treatments are being developed as a novel approach for the treatment of many diseases in an effort to repair injured tissues and regenerate lost tissues. Interest in the potential use of multipotent progenitor or stem cells has grown significantly in recent years, specifically the use of mesenchymal stem cells (MSCs), for tissue engineering in combination with extracellular matrix based scaffolds. An area that warrants further attention is the local or systemic host responses toward the implanted cell-biomaterial constructs. Such immunological responses could play a major role in determining the clinical efficacy of the therapeutic device or biomaterials used. MSCs, due to their unique immunomodulatory properties, hold great promise in tissue engineering as they not only directly participate in tissue repair and regeneration but also modulate the host foreign body response toward the engineered constructs. The purpose of this review was to summarize the current state of knowledge and applications of MSC-biomaterial constructs as a potential immunoregulatory tool in tissue engineering. Better understanding of the interactions between biomaterials and cells could translate to the development of clinically relevant and novel cell-based therapeutics for tissue reconstruction and regenerative medicine. PMID- 25140990 TI - Boron dipyrromethene as a fluorescent caging group for single-photon uncaging with long-wavelength visible light. AB - Caged compounds are useful tools for precise spatiotemporal modulation of cell functions, but in most cases uncaging requires ultraviolet (UV) light, which is cytotoxic and has limited tissue penetration. Therefore, caged compounds that can be activated by longer-wavelength light are required. Here we describe a novel photoelimination reaction of 4-aryloxy boron dipyrromethene (BODIPY) derivatives and show that BODIPY can function as a caging group for phenol groups. We developed a novel BODIPY-caged histamine compound, which is photoactivatable with blue-green visible light to stimulate cultured HeLa cells in a spatiotemporally well-controlled manner. This caging strategy is expected to be widely applicable to develop tools for probing various cellular functions. PMID- 25140991 TI - Tandem ring-closing metathesis/transfer hydrogenation: practical chemoselective hydrogenation of alkenes. AB - An operationally simple chemoselective transfer hydrogenation of alkenes using ruthenium metathesis catalysts is presented. Of great practicality, the transfer hydrogenation reagents can be added directly to a metathesis reaction and effect hydrogenation of the product alkene in a single pot at ambient temperature without the need to seal the vessel to prevent hydrogen gas escape. The reduction is applicable to a range of alkenes and can be performed in the presence of aryl halides and benzyl groups, a notable weakness of Pd-catalyzed hydrogenations. Scope and mechanistic considerations are presented. PMID- 25140992 TI - Profile hidden Markov models for the detection of viruses within metagenomic sequence data. AB - Rapid, sensitive, and specific virus detection is an important component of clinical diagnostics. Massively parallel sequencing enables new diagnostic opportunities that complement traditional serological and PCR based techniques. While massively parallel sequencing promises the benefits of being more comprehensive and less biased than traditional approaches, it presents new analytical challenges, especially with respect to detection of pathogen sequences in metagenomic contexts. To a first approximation, the initial detection of viruses can be achieved simply through alignment of sequence reads or assembled contigs to a reference database of pathogen genomes with tools such as BLAST. However, recognition of highly divergent viral sequences is problematic, and may be further complicated by the inherently high mutation rates of some viral types, especially RNA viruses. In these cases, increased sensitivity may be achieved by leveraging position-specific information during the alignment process. Here, we constructed HMMER3-compatible profile hidden Markov models (profile HMMs) from all the virally annotated proteins in RefSeq in an automated fashion using a custom-built bioinformatic pipeline. We then tested the ability of these viral profile HMMs ("vFams") to accurately classify sequences as viral or non-viral. Cross-validation experiments with full-length gene sequences showed that the vFams were able to recall 91% of left-out viral test sequences without erroneously classifying any non-viral sequences into viral protein clusters. Thorough reanalysis of previously published metagenomic datasets with a set of the best-performing vFams showed that they were more sensitive than BLAST for detecting sequences originating from more distant relatives of known viruses. To facilitate the use of the vFams for rapid detection of remote viral homologs in metagenomic data, we provide two sets of vFams, comprising more than 4,000 vFams each, in the HMMER3 format. We also provide the software necessary to build custom profile HMMs or update the vFams as more viruses are discovered (http://derisilab.ucsf.edu/software/vFam). PMID- 25140993 TI - Iodoaromatization reactions of enyne-dioxinones: syntheses of 4H-1,3-benzodioxin 4-ones, masked pentasubstituted arenes. AB - Sequential reaction of a keto-dioxinone with dimethylformamide dimethyl acetal and a range of magnesium acetylides gave the corresponding enyne-dioxinones as mixtures of E and Z isomers (E > Z). Subsequent reaction with iodine monochloride resulted in cycloaromatization, presumably via an iodovinyl cation, giving a range of 4H-1,3-benzodioxin-4-ones. PMID- 25140994 TI - Thyroid function and metabolic risk factors in obese youth. Changes during follow up: a preventive mechanism? AB - OBJECTIVES: High TSH levels often observed in overweight subjects are associated with metabolic risk. Thyroid hormones which are involved in fat and carbohydrates metabolism are more rarely studied; their blood levels were measured to more precisely explain the relationships between thyroid function and obesity, in healthy overweight youth. This correlation was studied at baseline and during follow-up of some patients. MATERIALS/METHODS: Data collected were BMI and BMI z score, thyroid hormones (TSH, fT4, fT3), fasting blood glucose, HOMA-IR, lipids (triglycerides, HDL and LDL cholesterol), transaminase activity, fibrinogen, leptin, IGF-I; body composition (biphotonic absorptiometry). Data collected in a sample of the group after 6-18 months of medical intervention could also be studied. RESULTS: At baseline, 13% of the 528 obese subjects (55% girls; 11.3+/ 2.4 years, range 4.1-17.9; BMI z score: 5.4+/-2.4) had TSH>4mUI/l; fT3 levels were associated with age and transaminase activity; using multivariate regression analysis, with z-score and age as covariates, fT4 showed correlations with TSH, insulin, HOMA IR, blood lipids, and fibrinogen. No correlations were found with leptin, iodine excretion, IGF-I.In 79 patients followed for 52+/-15 wk (45% girls; age range 8-18.3 years), univariate regression showed a positive correlation between changes in TSH and HOMA-IR, and between changes in fT4 and HDL. Multivariate regression analysis with z score as covariate showed that baseline TSH was associated with negative changes in HOMA-IR. CONCLUSIONS: Increased TSH may be predictive of a decrease in insulin resistance, it should be measured with thyroid hormones; fT4 was associated with a low metabolic risk. Changes in thyroid function could protect against the occurrence of obesity associated metabolic diseases. PMID- 25140995 TI - A 6-year follow-up of a randomized prospective trial comparing methimazole treatment with or without exogenous L-thyroxine in Chinese patients with Graves' disease. AB - OBJECTIVE: Antithyroid drug therapy is one of the main medical treatments for Graves' disease. There have been conflicting reports as to whether the addition of exogenous L-thyroxine improves remission rates more than antithyroid drugs alone. This randomized, controlled and prospective clinical trial was undertaken to investigate the long-term outcome of methimazole treatment with or without exogenous L-thyroxine in Chinese patients. METHODS: 145 patients with Graves' disease were randomly divided into 3 groups and all patients initially received 30 mg of methimazole daily for at least 1 month and then followed the titration regimen with or without L-thyroxine: group 1 (30 mg->20 mg->15 mg->10 mg->5 mg); group 2 (30 mg->20 mg->15 mg->10 mg+L-thyroxine->5 mg+L-thyroxine); group 3 (30 mg->20 mg->15 mg->10 mg+L-thyroxine->5 mg+L-thyroxine->2.5 mg+L-thyroxine). The drug therapy was discontinued after 5 months of the final dose. RESULTS: 16 out of 46 patients in group 1 (34.8%), 12 out of 47 in group 2 (25.5%) and 16 out of 52 in group 3 (30.8%) had a recurrence of Graves' disease within 6-year follow-up after drug withdrawal. Survival Analysis showed no significant differences in the remission rates between any 2 groups, despite the remission rates in group 2 and 3 were slightly higher than that in group 1. CONCLUSIONS: The addition of L thyroxine to methimazole treatment in patients with Graves' disease neither improves nor prevents the remission or recurrence of Graves' disease in China. PMID- 25140996 TI - Serum concentration of VEGF and PDGF-AA in patients with active thyroid orbitopathy before and after immunosuppressive therapy. AB - INTRODUCTION: Thyroid orbitopathy (TO) is the most frequent extrathyroid manifestation of Graves' disease. The aim of this study was to evaluate the serum concentration of Vascular Endothelial Growth Factor (VEGF), Plated-Derived Growth Factor-AA (PDGF-AA) in the blood of patients with active OT before and after immunosuppressive therapy. PATIENTS AND METHODS: The study was performed in group of 39 patients with clinically active TO (Group A) in euthyroid (n=18, Group A I) and hyperthyroid (n=21, Group A II) stage of Graves' disease in moderate or severe stage of TO. Control group consist of 20 healthy age-matched control subjects. Concentration of studied proangiogenic factors in serum samples were measured by an enzyme linked immunosorbent assay (ELISA) before (group A) and after (group A1) intensive pulse methylprednisolone treatment and one month after the end of additional oral methylprednisolone treatment (Group A2). RESULTS: We have found significant increased serum levels of VEGF in patients with TO (reg ardless to treatment) when compared with control group (542.4+/-328.1 pg/ml vs. 94.6+/-55.3 pg/ml, p=0.0002) and increased serum levels of -PDGF-AA in patients before treatment (3 173.6+/-1 480.3 pg/ml) in comparison with controls (1 768.9+/ 520.0 pg/ml) and patients after intensive pulse methyloprednisolone treatment (2 325.9+/-1 456.8 pg/ml). One month after the end of additional oral methylprednisolone treatment (Group A2) concentration of PDGF-AA still decreased and were was not significant difference with value in control group (1 853.1+/ 795.4 vs. 1 769.9+/-520.0 pg/ml, p=0.99). Serum concentration of VEGF was still significantly higher compared with control. We have not observed difference in serum concentration of studied proangiogenic factors between patients in euthyroid or hyperthyroid stage of Graves' disease. CONCLUSIONS: RESULTS of the present study confirm the fact that angiogenesis could play a role in pathogenesis of thyroid orbitopathy. PMID- 25140997 TI - The GLP-1 analogue liraglutide protects cardiomyocytes from high glucose-induced apoptosis by activating the Epac-1/Akt pathway. AB - BACKGROUND: Cardiomyocyte apoptosis is closely related to cardiac dysfunction in diabetic patients. Although GLP-1 analogs are used as anti-diabetic drugs, their effects on cardiomyocytes remain unclear. The aim of this study was to assess the effects of the GLP-1 analog liraglutide on high glucose-induced cardiomyocyte apoptosis. METHODS: Wistar rats were divided into normal (N), diabetes mellitus (DM), and liraglutide (LIR) groups. H9c2 cardiomyocytes were divided into normal (NG) and high glucose (HG) groups, 4 liraglutide groups (Lir1-4), 3 Epac-1 agonist intervention groups (CPT1-3), and 2 Epac-1 shRNA transfection groups (sh21 and sh22). Apoptosis was measured using TUNEL assays, and the apoptotic indices were calculated. Intracellular ROS levels were measured using a DCFH-DA probe. Epac-1, Akt, and P-Akt (Ser473) expression were measured by immunoblotting. RESULTS: The apoptotic index and intracellular ROS levels were higher in the HG than NG group (P<0.01). Liraglutide decreased both parameters in a dose- and time-dependent manner. Liraglutide increased the expression of Epac-1 in the myocardium of diabetic rats and H9c2 cells (P<0.05), and increased Akt phosphorylation in the myocardium of diabetic rats (P<0.05). Liraglutide treatment also increased the P-Akt (Ser473)/Akt ratio (P<0.05). An Epac-1 agonist increased Epac-1 expression (P<0.05) and the P-Akt (Ser473)/Akt ratio (P<0.05) in a dose-dependent manner, and subsequently decreased apoptosis and intracellular ROS. Conversely, Epac-1shRNA knocked-down Epac-1 expression (P<0.01) and decreased the P-Akt (Ser473)/Akt ratio (P<0.05), but had no effect on apoptosis and intracellular ROS levels. CONCLUSIONS: Liraglutide protects cardiomyocytes from high glucose-induced apoptosis by activating the Epac-1/Akt pathway. PMID- 25140998 TI - Chimpanzees and humans mimic pupil-size of conspecifics. AB - Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes). We conjectured that if pupil mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals. PMID- 25140999 TI - An early warning system based on syndromic surveillance to detect potential health emergencies among migrants: results of a two-year experience in Italy. AB - Profound geopolitical changes have impacted the southern and eastern Mediterranean since 2010 and defined a context of instability that is still affecting several countries today. Insecurity combined with the reduction of border controls has led to major population movements in the region and to migration surges from affected countries to southern Europe, especially to Italy. To respond to the humanitarian emergency triggered by this migration surge, Italy implemented a syndromic surveillance system in order to rapidly detect potential public health emergencies in immigrant reception centres. This system was discontinued after two years. This paper presents the results of this experience detailing its strengths and weaknesses in order to document the applicability and usefulness of syndromic surveillance in this specific context. PMID- 25141000 TI - Human leptospirosis trends: northeast Thailand, 2001-2012. AB - The objective of this study was to determine the changing trend of leptospirosis over time in Thailand using two prospective hospital-based studies conducted amongst adult patients with acute undifferentiated fever (AUFI) admitted to Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima Province, Thailand between July 2001 to December 2002 and between July 2011 to December 2012. During the first period, leptospirosis (98 patients, 40%) and scrub typhus (59 patients, 24.1%) were the two major causes of AUFI. In the second period, scrub typhus (137 patients, 28.3%) was found to be more common than leptospirosis (61 patients, 12.7%). Amongst patients with leptospirosis, the proportion of male patients and the median age were similar. Leptospira interrogans serogroup Autumnalis was the major infecting serogroup in both study periods. The case fatality rate of leptospirosis was significantly higher in 2011-2012 as compared with the case fatality rate in 2001-2002 (19.7% vs. 6.3%, p < 0.001). In summary, we found that number of leptospirosis cases had decreased over time. This trend is similar to reportable data for leptospirosis complied from passive surveillance by the Ministry of Public Health, Thailand. However, the case fatality rate of severe leptospirosis has increased. Severe lung hemorrhage associated with leptospirosis remained the major cause of death. PMID- 25141001 TI - HIV risky sexual behaviors and HIV infection among immigrants: a cross-sectional study in Lisbon, Portugal. AB - This study aimed to examine risky sexual behavior, its associated factors and HIV infection among immigrants. A participatory cross-sectional survey was conducted with 1187 immigrants at the National Immigrant Support Centre, in Lisbon (52.2% female; 34.0% Africans, 33.8% Brazilians, 32.2% Eastern Europeans). About 38% of participants reported >= 2 sexual partners in the previous year, 16.2% both regular and occasional sexual partners (last 12 months), 33.1% inconsistent condom use with occasional partners, and 64% no condom use in the last sexual intercourse. Unprotected sex in the last sexual intercourse was more likely among women, Africans, those older, with elementary education, those married and those who didn't receive free condoms in the previous year. No condom use was less likely among those having only occasional sexual partners and both regular and occasional sexual partners. One third of participants had never been tested for HIV. Those never tested reported more frequently inconsistent condom use than those ever tested. Overall, 2.0% reported being HIV positive (2.5% of men; 4.4% of Africans); 4.3% admitted having a STI in previous year. HIV-positive immigrants reported high-risk sexual behaviors. Tailored interventions to promote awareness of HIV serostatus among immigrants as well as culturally adapted risk reduction strategies should be strengthened. PMID- 25141002 TI - Histological lesions, cell cycle arrest, apoptosis and T cell subsets changes of spleen in chicken fed aflatoxin-contaminated corn. AB - The purpose of this study was to evaluate the effects of corn naturally contaminated with aflatoxin B1 and aflatoxin B2 on pathological lesions, apoptosis, cell cycle phases and T lymphocyte subsets of spleen, and to provide an experimental basis for understanding the mechanism of aflatoxin-induced immunosuppression. A total of 900 COBB500 male broilers were randomly allocated into five groups with six replicates per group and 30 birds per replicate. The experiment lasted for 6 weeks and the five dietary treatments consisted of control, 25% contaminated corn, 50% contaminated corn, 75% contaminated corn and 100% contaminated corn groups. The histopathological spleen lesions from the contaminated corn groups was characterized as congestion of red pulp, increased necrotic cells and vacuoles in the splenic corpuscle and periarterial lymphatic sheath. The contaminated corn intake significantly increased relative weight of spleen, percentages of apoptotic splenocytes, induced cell cycle arrest of splenocytes, increased the percentages of CD3+CD8+ T cells and decreased the ratios of CD3+CD4+ to CD3+CD8+. The results suggest that AFB-induced immunosuppression maybe closely related to the lesions of spleen. PMID- 25141003 TI - Influence of surfactant and lipid type on the physicochemical properties and biocompatibility of solid lipid nanoparticles. AB - Nine types of solid lipid nanoparticle (SLN) formulations were produced using tripalmitin (TPM), glyceryl monostearate (GM) or stearic acid (SA), stabilized with lecithin S75 and polysorbate 80. Formulations were prepared presenting PI values within 0.25 to 0.30, and the physicochemical properties, stability upon storage and biocompatibility were evaluated. The average particle size ranged from 116 to 306 nm, with a negative surface charge around -11 mV. SLN presented good stability up to 60 days. The SLN manufactured using SA could not be measured by DLS due to the reflective feature of this formulation. However, TEM images revealed that SA nanoparticles presented square/rod shapes with an approximate size of 100 nm. Regarding biocompatibility aspects, SA nanoparticles showed toxicity in fibroblasts, causing cell death, and produced high hemolytic rates, indicating toxicity to red blood cells. This finding might be related to lipid type, as well as, the shape of the nanoparticles. No morphological alterations and hemolytic effects were observed in cells incubated with SLN containing TPM and GM. The SLN containing TPM and GM showed long-term stability, suggesting good shelf-life. The results indicate high toxicity of SLN prepared with SA, and strongly suggest that the components of the formulation should be analyzed in combination rather than separately to avoid misinterpretation of the results. PMID- 25141005 TI - Insertions or deletions (Indels) in the rrn 16S-23S rRNA gene internal transcribed spacer region (ITS) compromise the typing and identification of strains within the Acinetobacter calcoaceticus-baumannii (Acb) complex and closely related members. AB - To determine whether ITS sequences in the rrn operon are suitable for identifying individual Acinetobacter Acb complex members, we analysed length and sequence differences between multiple ITS copies within the genomes of individual strains. Length differences in ITS reported previously between A. nosocomialis BCRC15417T (615 bp) and other strains (607 bp) can be explained by presence of an insertion (indel 13i/1) in the longer ITS variant. The same Indel 13i/1 was also found in ITS sequences of ten strains of A. calcoaceticus, all 639 bp long, and the 628 bp ITS of Acinetobacter strain BENAB127. Four additional indels (13i/2-13i/5) were detected in Acinetobacter strain c/t13TU 10090 ITS length variants (608, 609, 620, 621 and 630 bp). These ITS variants appear to have resulted from horizontal gene transfer involving other Acinetobacter species or in some cases unrelated bacteria. Although some ITS copies in strain c/t13TU 10090 are of the same length (620 bp) as those in Acinetobacter strains b/n1&3, A. pittii (10 strains), A. calcoaceticus and A. oleivorans (not currently acknowledged as an Acb member), their individual ITS sequences differ. Thus ITS length by itself can not by itself be used to identify Acb complex strains. A shared indel in ITS copies in two separate Acinetobacter species compromises the specificity of ITS targeted probes, as shown with the Aun-3 probe designed to target the ITS in A. pitti. The presence of indel 13i/5 in the ITS of Acinetobacter strain c/t13TU means it too responded positively to this probe. Thus, neither ITS sequencing nor the currently available ITS targeted probes can distinguish reliably between Acb member species. PMID- 25141004 TI - A novel zebrafish model to provide mechanistic insights into the inflammatory events in carrageenan-induced abdominal edema. AB - A suitable small animal model may help in the screening and evaluation of new drugs, especially those from natural products, which can be administered at lower dosages, fulfilling an urgent worldwide need. In this study, we explore whether zebrafish could be a model organism for carrageenan-induced abdominal edema. The research results showed that intraperitoneal (i.p.) administration of 1.5% lambda carrageenan in a volume of 20 uL significantly increased abdominal edema in adult zebrafish. Levels of the proinflammatory proteins tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) were increased in carrageenan-injected adult zebrafish during the development of abdominal edema. An associated enhancement was also observed in the leukocyte marker, myeloperoxidase (MPO). To support these results, we further observed that i.p. methylprednisolone (MP; 1 ug), a positive control, significantly inhibited carrageenan-induced inflammation 24 h after carrageenan administration. Furthermore, i.p. pretreatment with either an anti-TNF-alpha antibody (1?5 dilution in a volume of 20 uL) or the iNOS-selective inhibitor aminoguanidine (AG; 1 ug) inhibited carrageenan-induced abdominal edema in adult zebrafish. This new animal model is uncomplicated, easy to develop, and involves a straightforward inducement of inflammatory edema for the evaluation of small volumes of drugs or test compounds. PMID- 25141006 TI - A robust and adaptable high throughput screening method to study host-microbiota interactions in the human intestine. AB - The intestinal microbiota has many beneficial roles for its host. However, the precise mechanisms developed by the microbiota to influence the host intestinal cell responses are only partially known. The complexity of the ecosystem and our inability to culture most of these micro-organisms have led to the development of molecular approaches such as functional metagenomics, i.e. the heterologous expression of a metagenome in order to identify functions. This elegant strategy coupled to high throughput screening allowed to identify novel enzymes from different ecosystems where culture methods have not yet been adapted to isolate the candidate microorganisms. We have proposed to use this functional metagenomic approach in order to model the microbiota's interaction with the host by combining this heterologous expression with intestinal reporter cell lines. The addition of the cellular component to this functional metagenomic approach introduced a second important source of variability resulting in a novel challenge for high throughput screening. First attempts of high throughput screening with various reporter cell-lines showed a high distribution of the response and consequent difficulties to reproduce the response, impairing an easy and clear identification of confirmed hits. In this study, we developed a robust and reproducible methodology to combine these two biological systems for high throughput application. We optimized experimental setups and completed them by appropriate statistical analysis tools allowing the use this innovative approach in a high throughput manner and on a broad range of reporter assays. We herewith present a methodology allowing a high throughput screening combining two biological systems. Therefore ideal conditions for homogeneity, sensitivity and reproducibility of both metagenomic clones as well as reporter cell lines have been identified and validated. We believe that this innovative method will allow the identification of new bioactive microbial molecules and, subsequently, will promote understanding of host-microbiota interactions. PMID- 25141007 TI - Ant-plant interaction in a tropical savanna: may the network structure vary over time and influence on the outcomes of associations? AB - Plant-animal interactions occur in a community context of dynamic and complex ecological interactive networks. The understanding of who interacts with whom is a basic information, but the outcomes of interactions among associates are fundamental to draw valid conclusions about the functional structure of the network. Ecological networks studies in general gave little importance to know the true outcomes of interactions and how they may change over time. We evaluate the dynamic of an interaction network between ants and plants with extrafloral nectaries, by verifying the temporal variation in structure and outcomes of mutualism for the plant community (leaf herbivory). To reach this goal, we used two tools: bipartite network analysis and experimental manipulation. The networks exhibited the same general pattern as other mutualistic networks: nestedness, asymmetry and low specialization and this pattern was maintained over time, but with internal changes (species degree, connectance and ant abundance). These changes influenced the protection effectiveness of plants by ants, which varied over time. Our study shows that interaction networks between ants and plants are dynamic over time, and that these alterations affect the outcomes of mutualisms. In addition, our study proposes that the set of single systems that shape ecological networks can be manipulated for a greater understanding of the entire system. PMID- 25141008 TI - A pilot study of serum microRNAs panel as potential biomarkers for diagnosis of nonalcoholic fatty liver disease. AB - BACKGROUND: The invasive nature of liver biopsy makes the histopathological diagnosis of non-alcoholic fatty liver disease (NAFLD) difficult and its diagnostic performance unsatisfactory. The present study aimed to identify a serum microRNA (miRNA) expression profile that could serve as a novel diagnostic biomarker for NAFLD. METHODS: Serum miRNA expression was investigated using three cohorts comprising 465 participants (healthy controls and NAFLD patients) recruited between August 2010 and June 2013. miRNA expression was initially screened by Illumina sequencing using serum samples pooled from 20 patients and 20 controls. Quantitative reverse transcriptase polymerase chain reaction assay was then used to evaluate the expression of selected miRNAs. A logistic regression model was constructed using a training cohort (n = 242) and validated using another cohort (n = 183). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. RESULTS: We identified an miRNA panel (hsa-miR-122-5p, hsa-miR-1290, hsa-miR-27b-3p, and hsa miR-192-5p) with a high diagnostic accuracy for NAFLD. The satisfactory diagnostic performance of the miRNA panel remained regardless of the NAFLD activity score (NAS) status. There was significant difference between the AUC values of the miRNA panel and those of ALT (AUC = 0.786, 95% CI = 0.717-0.855; P = 0.142) and FIB-4 (AUC = 0.795, 95% CI = 0.730-0.860; sensitivity = 69.9%, specificity = 83.7%. CONCLUSION: We identified a serum microRNA panel with considerable clinical value in NAFLD diagnosis. The results indicate that the miRNA panel is a more sensitive and specific biomarker for NAFLD than ALT and FIB 4. PMID- 25141009 TI - IL-17A induces Pendrin expression and chloride-bicarbonate exchange in human bronchial epithelial cells. AB - The epithelium plays an active role in the response to inhaled pathogens in part by responding to signals from the immune system. Epithelial responses may include changes in chemokine expression, increased mucin production and antimicrobial peptide secretion, and changes in ion transport. We previously demonstrated that interleukin-17A (IL-17A), which is critical for lung host defense against extracellular bacteria, significantly raised airway surface pH in vitro, a finding that is common to a number of inflammatory diseases. Using microarray analysis of normal human bronchial epithelial (HBE) cells treated with IL-17A, we identified the electroneutral chloride-bicarbonate exchanger Pendrin (SLC26A4) as a potential mediator of this effect. These data were verified by real-time, quantitative PCR that demonstrated a time-dependent increase in Pendrin mRNA expression in HBE cells treated with IL-17A up to 48 h. Using immunoblotting and immunofluorescence, we confirmed that Pendrin protein expression is increased in IL-17 treated HBE cells and that it is primarily localized to the mucosal surface of the cells. Functional studies using live-cell fluorescence to measure intracellular pH demonstrated that IL-17A induced chloride-bicarbonate exchange in HBE cells that was not present in the absence of IL-17A. Furthermore, HBE cells treated with short interfering RNA against Pendrin showed substantially reduced chloride-bicarbonate exchange. These data suggest that Pendrin is part of IL-17A-dependent epithelial changes and that Pendrin may therefore be a therapeutic target in IL-17A-dependent lung disease. PMID- 25141011 TI - A systematic review on the development of asthma and allergic diseases in relation to international immigration: the leading role of the environment confirmed. AB - BACKGROUND: The prevalence of asthma and allergic diseases is rising worldwide. Evidence on potential causal pathways of asthma and allergies is growing, but findings have been contradictory, particularly on the interplay between allergic diseases and understudied social determinants of health like migration status. This review aimed at providing evidence for the association between migration status and asthma and allergies, and to explore the mechanisms between migration status and the development of asthma and allergies. METHODS AND FINDINGS: Systematic review on asthma and allergies and immigration status in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The pooled odds ratio (OR) of the prevalence of asthma in immigrants compared to the host population was 0.60 (95% CI 0.45-0.84), and the pooled OR for allergies was 1.01 (95% CI 0.62-1.69). The pooled OR for the prevalence of asthma in first generation versus second generation immigrants was 0.37 (95% CI 0.25-0.58). Comparisons between populations in their countries of origin and those that emigrated vary depending on their level of development; more developed countries show higher rates of asthma and allergies. CONCLUSIONS: Our findings suggest a strong influence of the environment on the development of asthma and allergic diseases throughout the life course. The prevalence of asthma is generally higher in second generation than first generation immigrants. With length of residence in the host country the prevalence of asthma and allergic diseases increases steadily. These findings are consistent across study populations, host countries, and children as well as adults. Differences have been found to be significant when tested in a linear model, as well as when comparing between early and later age of migration, and between shorter and longer time of residence. PMID- 25141012 TI - Hawthorne effect with transient behavioral and biochemical changes in a randomized controlled sleep extension trial of chronically short-sleeping obese adults: implications for the design and interpretation of clinical studies. AB - OBJECTIVE: To evaluate the effects of study participation per se at the beginning of a sleep extension trial between screening, randomization, and the run-in visit. DESIGN: Subjects were screened, returned for randomization (Comparison vs. Intervention) after 81 days (median), and attended run-in visit 121 days later. SETTING: Outpatient. PATIENTS: Obese (N = 125; M/F, 30/95; Blacks/Whites/Other, N = 73/44/8), mean weight 107.6+/-19.7 kg, <6.5 h sleep/night. INTERVENTION: Non pharmacological sleep extension. MEASUREMENTS: Sleep duration (diaries and actigraphy watch), sleep quality (Pittsburgh Sleep Quality Index), daily sleepiness (Epworth Sleepiness Scale), fasting glucose, insulin and lipids. RESULTS: Prior to any intervention, marked improvements occurred between screening and randomization. Sleep duration increased (diaries: 357.4 +/-51.2 vs. 388.1+/-48.6 min/night; mean+/-SD; P<0.001 screening vs. randomization; actigraphy: 344.3 +/-41.9 vs. 358.6+/-48.2 min/night; P<0.001) sleep quality improved (9.1+/-3.2 vs. 8.2+/-3.0 PSQI score; P<0.001), sleepiness tended to improve (8.9+/-4.6 vs. 8.3+/-4.5 ESS score; P = 0.06), insulin resistance decreased (0.327+/-0.038 vs. 0.351+/-0.045; Quicki index; P<0.001), and lipids improved, except for HDL-C. Abnormal fasting glucose (25% vs. 11%; P = 0.007), and metabolic syndrome (42% vs. 29%; P = 0.007) both decreased. In absence of intervention, the earlier metabolic improvements disappeared at the run-in visit. LIMITATIONS: Relatively small sample size. CONCLUSIONS: Improvements in biochemical and behavioral parameters between screening and randomization changed the "true" study baseline, thereby potentially affecting outcome. While regression to the mean and placebo effect were considered, these findings are most consistent with the "Hawthorne effect", according to which behavior measured in the setting of an experimental study changes in response to the attention received from study investigators. This is the first time that biochemical changes were documented with respect to the Hawthorne effect. The findings have implications for the design and conduct of clinical research. TRIAL REGISTRATION: ClinicalTrials.gov NCT00261898. PMID- 25141013 TI - Evaluating Darwin's naturalization hypothesis in experimental plant assemblages: phylogenetic relationships do not determine colonization success. AB - Darwin's naturalization hypothesis (DNH) proposes that colonization is less likely when the colonizing species is related to members of the invaded community, because evolutionary closeness intensifies competition among species that share similar resources. Studies that have evaluated DNH from correlational evidence have yielded controversial results with respect to its occurrence and generality. In the present study we carried out a set of manipulative experiments in which we controlled the phylogenetic relatedness of one colonizing species (Lactuca sativa) with five assemblages of plants (the recipient communities), and evaluated the colonizing success using five indicators (germination, growth, flowering, survival, and recruitment). The evolutionary relatedness was calculated as the mean phylogenetic distance between Lactuca and the members of each assemblage (MPD) and by the mean phylogenetic distance to the nearest neighbor (MNND). The results showed that the colonization success of Lactuca was not affected by MPD or MNND values, findings that do not support DNH. These results disagree with experimental studies made with communities of microorganisms, which show an inverse relation between colonization success and phylogenetic distances. We suggest that these discrepancies may be due to the high phylogenetic distance used, since in our experiments the colonizing species (Lactuca) was a distant relative of the assemblage members, while in the other studies the colonizing taxa have been related at the congeneric and conspecific levels. We suggest that under field conditions the phylogenetic distance is a weak predictor of competition, and it has a limited role in determining colonization success, contrary to prediction of the DNH. More experimental studies are needed to establish the importance of phylogenetic distance between colonizing species and invaded community on colonization success. PMID- 25141014 TI - Evaluation of the dentists' knowledge on medical urgency and emergency. AB - This study aimed at evaluating how well dentists understand medical emergency/urgency procedures and issues during dental treatment at a hospital specialized in cleft lip and palate. It comprised a hundred dentists from the Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo (HRAC/USP), Brazil, from different dental specialties. A questionnaire was applied to evaluate their knowledge of medical emergencies/urgencies from June through September 2011. The questionnaire was anonymous, confidential and constructed with closed questions and either yes-no or multiple-choice responses. Results showed that most professionals (87%) were trained in basic life support (BLS), but only 43% considered themselves capable of providing first aid and performing the necessary maneuvers. Most participants (94%) claimed that they knew the difference between medical urgencies and emergencies, and 69% had BLS training in their undergraduate courses, as opposed to 37%, during their specialization. Some participants (23%) mentioned that they had received knowledge of the subject during extracurricular courses and/or graduate courses (12%). Only 9% had not been educated on the subject; however, all participants showed interest in attending a course in BLS. In regard to assessing training that dentists who attended BLS courses received, 49% were satisfied and 42% were dissatisfied. Results of the present study emphasize that dentists from HRAC/USP have little knowledge about BLS procedures to perform them. Dentists must gain adequate education and training to minimize possible technical, ethical and legal problems associated with dental practice. It is necessary to improve both knowledge and practice in order to become well-qualified practitioners. PMID- 25141015 TI - Immediate loading implants with mandibular overdenture: a 48-month prospective follow-up study. AB - The aim of this prospective clinical study was to evaluate patient rehabilitation with two immediately loaded implants and bar-retained mandibular overdentures after 48 months of follow-up. Twenty patients were treated with two implants each; of these, 17 patients were re-evaluated for comparison. Gender, age, plaque index, gingival inflammation, keratinized mucosa, probing depth, bleeding, and implant loss data were recorded, and periapical radiographs were obtained for measurement of marginal bone loss. The results were statistically analyzed with one-way analysis of variance (ANOVA) followed by Student's t-test and Pearson's correlation test. To compare the data at baseline and after 48 months, a Wilcoxon Signed Rank Test was performed (alpha = 0.05). One implant failed (2.9%) during the first year and was replaced. A total of 35 implants were evaluated. Bone loss values were 0.52-2.89 mm (mean, 1.46 mm). Probing depth was 1.75-3.75 mm (mean, 2.22 mm). Correlations were found between bone loss and plaque index and between bone loss and gender, but bone loss did not correlate with gingival inflammation, keratinized mucosa, probing depth, or age. The overall survival rate of the implants was 97.1%. Based on these results, the use of two immediately loaded splinted interforaminal implants to retain an overdenture with a bar attachment is a clinically viable option with a high survival rate. PMID- 25141016 TI - Efficacy of chemomechanical caries removal in reducing cariogenic microbiota: a randomized clinical trial. AB - The aim of this study was to compare the efficacy of chemochemical methods (CarisolvTM and Papacarie(r)) versus the manual method (excavators) in reducing the cariogenic microbiota in dentine caries of primary teeth. Forty-six healthy children (5 to 9 years old) having at least one primary tooth with a cavitated dentine carious lesion were included in the study. The teeth presented no clinical or radiographic signs of pulpal involvement. The sample of 74 teeth was randomly divided into three different groups: Papacarie(r) (n = 25), CarisolvTM (n = 27) and Manual (n = 22). Samples of carious and sound dentine were collected with sterile excavators before and after caries removal in the three groups. The dentine samples were transferred to glass tubes containing a 1mL thioglycollate medium used as a carrier and enriched for microbiological detection of mutans streptococci and Lactobacillus spp, after incubation for 6h at room temperature. The minimum detection value for colony forming units (CFU) was 3.3 x 102 CFU/ml, and the results were converted into scores from 0 to 4. A significant difference was observed in relation to the microbiological scores before and after caries removal for all methods (Wilcoxon test; p < 0.001). The use of chemomechanical methods for caries removal did not improve the reduction of cariogenic microorganisms in dentine caries lesions, in comparison with manual excavation. PMID- 25141017 TI - Association between tooth loss and overweight/obesity among Brazilian adults: the Pro-Saude Study. AB - The aim of this study was to evaluate the association between tooth loss and overweight/obesity in an adult Brazilian population. It is a cross-sectional study comprising 3,930 adults [1,744 men and 2,186 women; median age of 40 y (ranging 20-59); 16.9% obese; 7.3% almost all or all teeth missing]. Data were collected using a self-administered questionnaire for tooth loss (4 categories), diet, access and use of health services, socioeconomic factors, health habits and behaviors, demographics and anthropometric measurements. Multiple ordinal logistic regressions were performed. In comparison with adults with BMI < 25 kg/m2, the overweight (BMI >= 25 and < 30kg/m2) and obese individuals (BMI >= 30 kg/m2) showed a greater odds of tooth loss (OR = 1.6, 95% CI 1.4-1.9 and OR = 2.1, 95% CI 1.8-2.5, respectively). After adjusting for potential confounders, overweight and obesity showed no statistically significant associations with tooth loss, with OR = 0.8 and OR = 0.9, respectively. The results of this study are consistent with the hypothesis that the association between overweight/obesity and tooth loss can be explained by known, common risk factors. PMID- 25141018 TI - Validation of a measuring instrument for the perception of oral health in women. AB - The aim of this study was to estimate the reliability, validity and factorial invariance of the Portuguese version of the Geriatric/General Oral Health Assessment Index (GOHAI) as applied to Brazilian women. A total 701 women over 18 years of age participated in this study. Telephone interviews were conducted. We evaluated the construct-related validity through factorial, convergent and discriminant validity. We carried out a confirmatory factor analysis using the chi2/df, CFI, GFI and RMSEA indexes. The invariance of the model in a second independent sample was estimated by multi-group analysis and internal consistency using Cronbach's alpha coefficient. Items 5 and 9 presented factor weights below the adequate value and were removed. The three-dimensional and unifactorial model presented an adequate fit. We observed strong factorial invariance of the models in two independent samples (three-factor: rholambda = 0.62; pCov = 0.89, one factor: rholambda = 0.81; pCov = 0.68) and weak factorial invariance between users and nonusers of dental prosthetics (three-factor: rholambda = 0.55; pCov = 0.01, one-factor: rholambda = 0.51; pCov = 0.02). The convergent validity was suboptimal. Internal consistency was adequate. The GOHAI applied to the study sample showed adequate reliability, factorial validity and stability in independent samples and between users and nonusers of dental prosthetics in both the three-dimensional and the unifactorial structures. PMID- 25141019 TI - Modeling the pre-industrial roots of modern super-exponential population growth. AB - To Malthus, rapid human population growth-so evident in 18th Century Europe-was obviously unsustainable. In his Essay on the Principle of Population, Malthus cogently argued that environmental and socioeconomic constraints on population rise were inevitable. Yet, he penned his essay on the eve of the global census size reaching one billion, as nearly two centuries of super-exponential increase were taking off. Introducing a novel extension of J. E. Cohen's hallmark coupled difference equation model of human population dynamics and carrying capacity, this article examines just how elastic population growth limits may be in response to demographic change. The revised model involves a simple formalization of how consumption costs influence carrying capacity elasticity over time. Recognizing that complex social resource-extraction networks support ongoing consumption-based investment in family formation and intergenerational resource transfers, it is important to consider how consumption has impacted the human environment and demography--especially as global population has become very large. Sensitivity analysis of the consumption-cost model's fit to historical population estimates, modern census data, and 21st Century demographic projections supports a critical conclusion. The recent population explosion was systemically determined by long-term, distinctly pre-industrial cultural evolution. It is suggested that modern globalizing transitions in technology, susceptibility to infectious disease, information flows and accumulation, and economic complexity were endogenous products of much earlier biocultural evolution of family formation's embeddedness in larger, hierarchically self organizing cultural systems, which could potentially support high population elasticity of carrying capacity. Modern super-exponential population growth cannot be considered separately from long-term change in the multi-scalar political economy that connects family formation and intergenerational resource transfers to wider institutions and social networks. PMID- 25141020 TI - Left preference for sport tasks does not necessarily indicate left-handedness: sport-specific lateral preferences, relationship with handedness and implications for laterality research in behavioural sciences. AB - In the elite domain of interactive sports, athletes who demonstrate a left preference (e.g., holding a weapon with the left hand in fencing or boxing in a 'southpaw' stance) seem overrepresented. Such excess indicates a performance advantage and was also interpreted as evidence in favour of frequency-dependent selection mechanisms to explain the maintenance of left-handedness in humans. To test for an overrepresentation, the incidence of athletes' lateral preferences is typically compared with an expected ratio of left- to right-handedness in the normal population. However, the normal population reference values did not always relate to the sport-specific tasks of interest, which may limit the validity of reports of an excess of 'left-oriented' athletes. Here we sought to determine lateral preferences for various sport-specific tasks (e.g., baseball batting, boxing) in the normal population and to examine the relationship between these preferences and handedness. To this end, we asked 903 participants to indicate their lateral preferences for sport-specific and common tasks using a paper-based questionnaire. Lateral preferences varied considerably across the different sport tasks and we found high variation in the relationship between those preferences and handedness. In contrast to unimanual tasks (e.g., fencing or throwing), for bimanually controlled actions such as baseball batting, shooting in ice hockey or boxing the incidence of left preferences was considerably higher than expected from the proportion of left-handedness in the normal population and the relationship with handedness was relatively low. We conclude that (i) task specific reference values are mandatory for reliably testing for an excess of athletes with a left preference, (ii) the term 'handedness' should be more cautiously used within the context of sport-related laterality research and (iii) observation of lateral preferences in sports may be of limited suitability for the verification of evolutionary theories of handedness. PMID- 25141021 TI - Asthma during pregnancy in a population-based study--pregnancy complications and adverse perinatal outcomes. AB - BACKGROUND: Asthma is one of the most common chronic diseases, and prevalence, severity and medication may have an effect on pregnancy. We examined maternal asthma, asthma severity and control in relation to pregnancy complications, labour characteristics and perinatal outcomes. METHODS: We retrieved data on all singleton births from July 1, 2006 to December 31, 2009, and prescribed drugs and physician-diagnosed asthma on the same women from multiple Swedish registers. The associations were estimated with logistic regression. RESULTS: In total, 266 045 women gave birth to 284 214 singletons during the study period. Maternal asthma was noted in 26 586 (9.4%) pregnancies. There was an association between maternal asthma and increased risks of pregnancy complications including preeclampsia or eclampsia (adjusted OR 1.15; 95% CI 1.06-1.24) and premature contractions (adj OR 1.52; 95% CI 1.29-1.80). There was also a significant association between maternal asthma and emergency caesarean section (adj OR 1.29; 95% CI 1.23-1.34), low birth weight, and small for gestational age (adj OR 1.23; 95% CI 1.13-1.33). The risk of adverse outcomes such as low birth weight increased with increasing asthma severity. For women with uncontrolled compared to those with controlled asthma the results for adverse outcomes were inconsistent displaying both increased and decreased OR for some outcomes. CONCLUSION: Maternal asthma is associated with a number of serious pregnancy complications and adverse perinatal outcomes. Some complications are even more likely with increased asthma severity. With greater awareness and proper management, outcomes would most likely improve. PMID- 25141022 TI - Enzymatic size control of RNA particles using complementary rolling circle transcription (cRCT) method for efficient siRNA production. AB - A novel fabrication method for RNA particles (RPs) was developed based on enzymatic polymerization, and the size of the RPs was controlled intentionally by adjusting the RNA polymerase concentration for a variety of potential applications. PMID- 25141023 TI - Investigation of the role of protonation of benzophenone and its derivatives in acidic aqueous solutions using time-resolved resonance Raman spectroscopy: how are ketyl radicals formed in aqueous solutions? AB - The formation mechanism of ketyl radicals and several other selective photoreactions of benzophenone and its derivatives are initiated by the protonation of their triplet state and have been investigated using nanosecond time-resolved resonance Raman spectroscopy (ns-TR(3)) in solutions of varying conditions. Evidence is found that the ketyl radical is generated by the combined action of a ketone protonation and a subsequent electron transfer based on the results from previous studies on the photochemistry and photophysics of benzophenone and the ns-TR(3) results reported here for benzophenone, 1,4 dibenzoylbenzene, 3-(hydroxymethyl)benzophenone, and ketoprofen in neutral and acidic solution. In order to better understand the role of the protonated ketone, results are summarized for some selective photochemical reactions of benzophenone and its derivatives induced by protonation in acidic solutions. For the parent benzophenone, the protonation of the ketone leads to the photohydration reactions at the ortho- and meta-positions of the benzene ring in acidic aqueous solutions. For 3-(hydroxymethyl)benzophenone, the protonation promotes an interesting photoredox reaction to become very efficient and the predominant reaction in a pH = 2 aqueous solution. While for ketoprofen, the protonation can initiate a solvent-mediated excited-state intramolecular proton transfer (ESIPT) from the carboxyl group to the carbonyl group that then leads to a decarboxylation reaction in a pH = 0 acidic aqueous solution. We briefly discuss the key role of the protonation of the ketone in the photochemistry of these aromatic ketones. PMID- 25141024 TI - Aryl hydrocarbon receptor negatively regulates NLRP3 inflammasome activity by inhibiting NLRP3 transcription. AB - NLRP3 inflammasome is a multi-protein complex, which plays crucial roles in host defense against pathogens. The NLRP3 protein level is considered rate limiting for the activation of the inflammasome, thus its expression must be tightly controlled to maintain immune homeostasis. However, the molecular mechanisms that modulate NLRP3 expression, especially at the transcriptional level, remain largely unknown. In the present study, we show that aryl hydrocarbon receptor (AhR) activation inhibits NLRP3 expression, caspase-1 activation and subsequent IL-1beta secretion in peritoneal macrophages, whereas siRNA knockdown of AhR has opposite effects. AhR could bind to the xenobiotic response element (XRE) in the NLRP3 promoter and inhibit NLRP3 transcription. Furthermore, AhR activation suppresses Alum-induced peritonitis in vivo. Therefore, we identified AhR as a negative regulator of NLRP3 inflammasome activity by inhibiting the transcription of NLRP3 and suggested AhR as a potential target for the intervention of diseases with uncontrolled inflammasome activation. PMID- 25141025 TI - Isolation and propagation of neural crest stem cells from mouse embryonic stem cells via cranial neurospheres. AB - The developmental fate of the multipotent neural crest (NC) is determined along with the neural axis in which NC cells are generated. Only the cranial NC can differentiate into mesectodermal derivatives such as osteoblasts, chondrocytes, and adipocytes in vivo. Here, we attempted to selectively differentiate mouse embryonic stem (ES) cells into cranial NC stem cells and propagate them to explore their developmental potential to differentiate into mesectodermal derivatives. Using aggregation cultures in feeder- and serum-free neural induction medium (NIM) without serum replacement and l-glutamine, we obtained NIM neurospheres composed of neuroepithelium. The NIM neurospheres expressed the rostral markers Otx1 and Otx2, but not nonrostral markers Hoxb4, Hoxb9, Lbx1, and TH, which characterize cranial neurospheres. Subsequently, AP2alpha, Sox9, p75, Snail, Slug, and Twist-positive NC cells were differentiated in 4-day adhesion cultures of cranial neurospheres. In addition, sphere clusters in adhesion cultures were differentiated into osteoblasts, while migrating cells were not. By taking advantage of the sphere-formation capability, we isolated and propagated NC stem cells from the sphere clusters and confirmed their multipotency. NC stem cells expressed NC and stem cell markers, and they maintained differentiation potency in the NC derivatives. These results show that cranial NC stem cells were obtained reproducibly and efficiently without special inducing factors, gene transfection, or fluorescence-activated cell sorting selection. PMID- 25141026 TI - Modulation of stress versus time product during mechanical ventilation influences inflammation as well as alveolar epithelial and endothelial response in rats. AB - BACKGROUND: Mechanical ventilation can lead to lung biotrauma when mechanical stress exceeds safety thresholds. The authors investigated whether the duration of mechanical stress, that is, the impact of a stress versus time product (STP), influences biotrauma. The authors hypothesized that higher STP levels are associated with increased inflammation and with alveolar epithelial and endothelial cell injury. METHODS: In 46 rats, Escherichia coli lipopolysaccharide (acute lung inflammation) or saline (control) was administered intratracheally. Both groups were protectively ventilated with inspiratory-to-expiratory ratios 1:2, 1:1, or 2:1 (n = 12 each), corresponding to low, middle, and high STP levels (STPlow, STPmid, and STPhigh, respectively). The remaining 10 animals were not mechanically ventilated. RESULTS: In animals with mild acute lung inflammation, but not in controls: (1) messenger RNA expression of interleukin-6 was higher in STPhigh (28.1 +/- 13.6; mean +/- SD) and STPlow (28.9 +/- 16.0) versus STPmid (7.4 +/- 7.5) (P < 0.05); (2) expression of the receptor for advanced glycation end-products was increased in STPhigh (3.6 +/- 1.6) versus STPlow (2.3 +/- 1.1) (P < 0.05); (3) alveolar edema was decreased in STPmid (0 [0 to 0]; median, Q1 to Q3) compared with STPhigh (0.8 [0.6 to 1]) (P < 0.05); and (4) expressions of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 were higher in STPlow (3.0 +/- 1.8) versus STPhigh (1.2 +/- 0.5) and STPmid (1.4 +/- 0.7) (P < 0.05), respectively. CONCLUSIONS: In the mild acute lung inflammation model used herein, mechanical ventilation with inspiratory-to-expiratory of 1:1 (STPmid) minimized lung damage, whereas STPhigh increased the gene expression of biological markers associated with inflammation and alveolar epithelial cell injury and STPlow increased markers of endothelial cell damage. PMID- 25141027 TI - Modeling, molecular dynamics simulation, and mutation validation for structure of cannabinoid receptor 2 based on known crystal structures of GPCRs. AB - The cannabinoid receptor 2 (CB2) plays an important role in the immune system. Although a few of GPCRs crystallographic structures have been reported, it is still challenging to obtain functional transmembrane proteins and high resolution X-ray crystal structures, such as for the CB2 receptor. In the present work, we used 10 reported crystal structures of GPCRs which had high sequence identities with CB2 to construct homology-based comparative CB2 models. We applied these 10 models to perform a prescreen by using a training set consisting of 20 CB2 active compounds and 980 compounds randomly selected from the National Cancer Institute (NCI) database. We then utilized the known 170 cannabinoid receptor 1 (CB1) or CB2 selective compounds for further validation. Based on the docking results, we selected one CB2 model (constructed by beta1AR) that was most consistent with the known experimental data, revealing that the defined binding pocket in our CB2 model was well-correlated with the training and testing data studies. Importantly, we identified a potential allosteric binding pocket adjacent to the orthosteric ligand-binding site, which is similar to the reported allosteric pocket for sodium ion Na(+) in the A2AAR and the delta-opioid receptor. Our studies in correlation of our data with others suggested that sodium may reduce the binding affinities of endogenous agonists or its analogs to CB2. We performed a series of docking studies to compare the important residues in the binding pockets of CB2 with CB1, including antagonist, agonist, and our CB2 neutral compound (neutral antagonist) XIE35-1001. Then, we carried out 50 ns molecular dynamics (MD) simulations for the CB2 docked with SR144528 and CP55940, respectively. We found that the conformational changes of CB2 upon antagonist/agonist binding were congruent with recent reports of those for other GPCRs. Based on these results, we further examined one known residue, Val113(3.32), and predicted two new residues, Phe183 in ECL2 and Phe281(7.35), that were important for SR144528 and CP55940 binding to CB2. We then performed site-directed mutation experimental study for these residues and validated the predictions by radiometric binding affinity assay. PMID- 25141028 TI - Survival after acute hemodialysis in Pennsylvania, 2005-2007: a retrospective cohort study. AB - BACKGROUND: Little is known about acute hemodialysis in the US. Here we describe predictors of receipt of acute hemodialysis in one state and estimate the marginal impact of acute hemodialysis on survival after accounting for confounding due to illness severity. MATERIALS AND METHODS: This is a retrospective cohort study of acute-care hospitalizations in Pennsylvania from October 2005 to December 2007 using data from the Pennsylvania Health Care Cost Containment Council. Exposure variable is acute hemodialysis; dependent variable is survival following acute hemodialysis. We used multivariable logistic regression to determine propensity to receive acute hemodialysis and then, for a Cox proportional hazards model, matched acute hemodialysis and non-acute hemodialysis patients 1?5 on this propensity. RESULTS: In 2,131,248 admissions of adults without end-stage renal disease, there were 6,657 instances of acute hemodialysis. In analyses adjusted for predicted probability of death upon admission plus other covariates and stratified on age, being male, black, and insured were independent predictors of receipt of acute hemodialysis. One-year post-admission mortality was 43% for those receiving acute hemodialysis, compared to 13% among those not receiving acute hemodialysis. After matching on propensity to receive acute hemodialysis and adjusting for predicted probability of death upon admission, patients who received acute hemodialysis had a higher risk of death than patients who did not over at least 1 year of follow-up (hazard ratio 1.82, 95% confidence interval 1.68-1.97). CONCLUSIONS: In a populous US state, receipt of acute hemodialysis varied by age, sex, race, and insurance status even after adjustment for illness severity. In a comparison of patients with similar propensity to receive acute hemodialysis, those who did receive it were less likely to survive than those who did not. These findings raise questions about reasons for lack of benefit. PMID- 25141029 TI - The B35 cluster with a double-hexagonal vacancy: a new and more flexible structural motif for borophene. AB - Elemental boron is electron-deficient and cannot form graphene-like structures. Instead, triangular boron lattices with hexagonal vacancies have been predicted to be stable. A recent experimental and computational study showed that the B36 cluster has a planar C6v structure with a central hexagonal hole, providing the first experimental evidence for the viability of atom-thin boron sheets with hexagonal vacancies, dubbed borophene. Here we report a boron cluster with a double-hexagonal vacancy as a new and more flexible structural motif for borophene. Photoelectron spectrum of B35(-) displays a simple pattern with certain similarity to that of B36(-). Global minimum searches find that both B35( ) and B35 possess planar hexagonal structures, similar to that of B36, except a missing interior B atom that creates a double-hexagonal vacancy. The closed-shell B35(-) is found to exhibit triple pi aromaticity with 11 delocalized pi bonds, analogous to benzo(g,h,i)perylene (C22H12). The B35 cluster can be used to build atom-thin boron sheets with various hexagonal hole densities, providing further experimental evidence for the viability of borophene. PMID- 25141030 TI - Synthesis and electrochemical study of a hybrid structure based on PDMS-TEOS and titania nanotubes for biomedical applications. AB - Metallic implants and devices are widely used in the orthopedic and orthodontic clinical areas. However, several problems regarding their adhesion with the living tissues and inflammatory responses due to the release of metallic ions to the medium have been reported. The modification of the metallic surfaces and the use of biocompatible protective coatings are two approaches to solve such issues. In this study, in order to improve the adhesion properties and to increase the corrosion resistance of metallic Ti substrates we have obtained a hybrid structure based on TiO2 nanotubular arrays and PDMS-TEOS films. TiO2 nanotubes have been prepared with two different diameters by means of electrochemical anodization. PDMS-TEOS films have been prepared by the sol-gel method. The morphological and the elemental analysis of the structures have been investigated by scanning electron microscopy and energy dispersive spectroscopy (EDS). Electrochemical impedance spectroscopy (EIS) and polarization curves have been performed during immersion of the samples in Kokubo's simulated body fluid (SBF) at 37 degrees C to study the effect of structure layers and tube diameter on the protective properties. The obtained results show that the modification of the surface structure of TiO2 and the application of PDMS-TEOS film is a promising strategy for the development of implant materials. PMID- 25141031 TI - Ferroelectric Sm-doped BiMnO3 thin films with ferromagnetic transition temperature enhanced to 140 K. AB - A combined chemical pressure and substrate biaxial pressure crystal engineering approach was demonstrated for producing highly epitaxial Sm-doped BiMnO(3) (BSMO) films on SrTiO(3) single crystal substrates, with enhanced magnetic transition temperatures, TC up to as high as 140 K, 40 K higher than that for standard BiMnO(3) (BMO) films. Strong room temperature ferroelectricity with piezoresponse amplitude, d(33) = 10 pm/V, and long-term retention of polarization were also observed. Furthermore, the BSMO films were much easier to grow than pure BMO films, with excellent phase purity over a wide growth window. The work represents a very effective way to independently control strain in-plane and out-of-plane, which is important not just for BMO but for controlling the properties of many other strongly correlated oxides. PMID- 25141032 TI - Monitoring thrombin generation and screening anticoagulants through pulse laser induced fragmentation of biofunctional nanogold on cellulose membranes. AB - Thrombin generation (TG) has an important part in the blood coagulation system, and monitoring TG is useful for diagnosing various health issues related to hypo coagulability and hyper-coagulability. In this study, we constructed probes by using mixed cellulose ester membranes (MCEMs) modified with gold nanoparticles (Au NPs) for monitoring thrombin activity using laser desorption/ionization mass spectrometry (LDI-MS). The LDI process produced Au cationic clusters ([Au(n)](+); n = 1-3) that we detected through MS. When thrombin reacted with fibrinogen on the Au NPs-MCEMs, insoluble fibrin was formed, hindering the formation of Au cationic clusters and, thereby, decreasing the intensity of their signals in the mass spectrum. Accordingly, we incorporated fibrinogen onto the Au NPs-MCEMs to form Fib-Au NPs-MCEM probes to monitor TG with good selectivity (>1000-fold toward thrombin with respect to other proteins or enzymes) and sensitivity (limit of detection for thrombin of ca. 2.5 pM in human plasma samples). Our probe exhibited remarkable performance in monitoring the inhibition of thrombin activity by direct thrombin inhibitors. Analyses of real samples using our new membrane-based probe suggested that it will be highly useful in practical applications for the effective management of hemostatic complications. PMID- 25141033 TI - Adult-Adult and Adult-Child/Adolescent Online Sexual Interactions: An Exploratory Self-Report Study on the Role of Situational Factors. AB - Alcohol intoxication, sexual arousal, and negative emotional states have been found to precede certain sexual behaviors. Using data from an online self-report survey distributed to adults (N = 717; 423 men and 304 women), we compared adults with adult online sexual interactions (n = 640; 89.3%) to adults with interactions with a child or an adolescent (n = 77; 10.7%) on how much they reported being affected by the following factors surrounding the time of the interactions: alcohol intoxication, sexual arousal, sadness, boredom, stress, and shame. We found that those with a child or adolescent contact reported higher sexual arousal and more shame before the interaction, compared with those with an adult contact. In addition, the levels of negative emotional states varied when levels before the interactions were compared with levels after the interactions, suggesting that engaging in online sexual interactions alleviated negative emotional states, at least temporarily. The alleviatory effects, however, were accompanied by higher levels of shame after the interactions. Overall, adults that engage in online sexual interactions have remarkably similar perceptions of the situation surrounding these activities, independent of the age of their online contacts. Limitations of the study are discussed. PMID- 25141035 TI - Mipu1 overexpression protects macrophages from oxLDL-induced foam cell formation and cell apoptosis. AB - Mipu1 (myocardial ischemic preconditioning upregulated protein 1) is a novel N terminal Kruppel-associated box (KRAB)/C2H2 zinc finger superfamily protein, that displays a powerful effect in protecting H9c2 cells from oxidative stress-induced cell apoptosis. The present study aims to investigate the effect of Mipu1 overexpression on oxidized low-density lipoprotein (oxLDL)-induced foam cell formation, cell apoptosis, and its possible mechanisms. New Zealand healthy rabbits were used to establish atherosclerosis model, and serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low density lipoprotein cholesterol were detected by an automatic biochemical analyzer. Sudan IV staining was used to detect atherosclerotic lesions. The RAW264.7 macrophage cell line was selected as the experimental material. Oil red O staining, high-performance liquid chromatography, and Dil-labeled lipoprotein were used to detect cholesterol accumulation qualitatively and quantitatively, respectively. Flow cytometry was used to determine cell apoptosis. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expression of the main proteins that are associated with the transport of cholesterol, such as ABCA1, ABCG1, SR-BI, and CD36. Western blot analysis was used to detect the protein expression of Mipu1. There were atherosclerotic lesions in the high-fat diet group with Sudan IV staining. High-fat diet decreased Mipu1 expression and increased CD36 expression significantly at the 10th week compared with standard-diet rabbits. Mipu1 overexpression decreased oxLDL-induced cholesterol accumulation, oxLDL uptake, cell apoptosis, and cleaved caspase-3. Mipu1 overexpression inhibited the oxLDL-induced CD36 mRNA and protein expression, but it did not significantly inhibit the mRNA expression of ABCA1, ABCG1, and SR-BI. Mipu1 overexpression inhibits oxLDL-induced foam cell formation and cell apoptosis. Mipu1 overexpression reduces the lipid intake of macrophages and might be associated with the downregulation of CD36 expression in the presence of oxLDL. PMID- 25141037 TI - Dinuclear Ru/Ni, Ir/Ni, and Ir/Pt complexes with bridging phenanthroline-5,6 dithiolate: synthesis, structure, and electrochemical and photophysical behavior. AB - We report the synthesis and full characterization of dinuclear complexes with the bridging ligand phenanthroline-5,6-dithiolate (phendt(2-)) featuring the [Ru(bpy)2](2+) or Ir(ppy)2](+) fragment at the diimine donor center and the [Ni(dppe)](2+) or [Pt(phen)](2+) complex moiety at the dithiolate group. The molecular structures of the mononuclear complexes [(C5H5)2Ti(S,S'-phendt)] and [(ppy)2Ir{N,N'-phendt-(C2H4CN)2}](PF6) as well as the dinuclear complex [(C5H5)(PPh3)Ru(phendt)Ni(dppe)](PF6) determined by X-ray diffraction (XRD) studies are compared. Photophysical studies with mononuclear [(bpy)2Ru{phendt (C2H4CN)2}](2+) and [(ppy)2Ir{phendt-(C2H4CN)2}](+) as well as dinuclear [(bpy)2Ru(phendt)Ni(dppe)](2+) and [(ppy)2Ir(phendt)Ni(dppe)](+) uncovered an effective luminescence quenching in the dinuclear complexes. Lifetime measurements at room temperature, steady-state measurements at low temperature, electrochemical investigations, and DFT calculations provide evidence for a very efficient energy transfer from the Ru/Ir to the Ni complex moiety with a rate constant k > 5 * 10(9) s(-1). In comparison, the [Ru]phendt[Ni] complex displays a higher quenching efficiency with reduced excited state lifetime, whereas the [Ir]phendt[Ni] complex is characterized by an unaltered lifetime of the thermally equilibrated excited state. PMID- 25141038 TI - Self-reported depression and anxiety after prenatal famine exposure: mediation by cardio-metabolic pathology? AB - Evidence from previous studies suggests an association between prenatal exposure to famine and increased risk for depression. The aim of this study was to investigate whether prenatal exposure to the Dutch famine is associated with self reported depression/anxiety and whether a potential association is mediated by the presence of cardio-metabolic disease. A total of 819 persons, born as term singletons around the 1944-1945 Dutch famine, filled out the Hospital Anxiety and Depression Scale (HADS) and were asked about their medical history. As indicators of cardio-metabolic disease we included type 2 diabetes (T2D), hypertension and coronary heart disease (CHD). In the total study population, exposure to famine during early gestation was associated with the presence of self-reported mild-to severe anxiety. Evidence was found for several interactions between exposure in early gestation and sex. Subsequent analyses according to sex showed that men exposed to famine during early gestation scored higher on the HADS depression scale. Self-reported mild-to-severe anxiety symptoms were more prevalent among early exposed men. No such differences were found in women. T2D and hypertension were not correlated with any of the depression and anxiety measures. Adjusting for the presence of CHD did minimally attenuate the size of the reported associations. In conclusion, the present results do not match those previously reported in prenatally famine-exposed individuals. We found only weak evidence for an association between prenatal famine exposure and symptoms of depression and anxiety, which was shown exclusively in men exposed during early gestation. PMID- 25141039 TI - Anthropometry from birth to 24 months among offspring of women with gestational diabetes: 2004 Pelotas Birth Cohort. AB - The aim of this study was to compare physical growth from birth to 2 years of age of babies born to women with or without gestational diabetes mellitus (GDM), among the subjects of the 2004 Pelotas Birth Cohort. Mothers who gave birth in 2004 in any of the five maternity wards in the city of Pelotas, Southern Brazil, were interviewed shortly after delivery by trained interviewers, using tested, pre-coded questionnaires. GDM diagnosis was self-reported. Child weight, length and abdominal circumference were measured, and adjusted weight-for-age, height for-age and weight-for-height Z-scores were calculated at birth, 3, 12 and 24 months. We studied 4239 children. Offspring of GDM mothers (OGDM; n = 125) had lower gestational age (GA; P = 0.004), greater weight (P = 0.002) and greater abdominal circumference (P < 0.001) at birth. Prevalence of large for GA (LGA) was threefold higher among OGDM (18.4% v. 6.8%). Mean weight-for-age (0.48 v. 0.07; P < 0.001) and weight-for-height (0.94 v. 0.51; P < 0.001) Z-scores were also higher among OGDM. During the first 3 months, there was an abrupt catch-down among OGDM babies, who remained lighter than non-GDM offspring until the 24th month. LGA OGDM were heavier than LGA offspring of non-GDM mothers at birth, but had caught down with babies born with adequate weight for GA to non-GDM by 3 months, and showed similar growth patterns from thereon. OGDM show different growth patterns when compared to offspring of non-GDM mothers, which may be part of a causal pathway or constitute a risk marker for future obesity, impaired glucose tolerance and diabetes mellitus. PMID- 25141040 TI - Psychosocial determinants of cigarette smoking among university students in Jordan. AB - The objectives of this study were to describe the prevalence of cigarette use and water pipe smoking in Jordanian university students and to analyze differences in determinants between cigarette smokers and non-smokers. A cross-sectional questionnaire was administered to a random sample of 400 students (18-24 years, 51% males). Smokers were compared with non-smokers on several smoking-related determinants. Data were analyzed using descriptive statistics, t-test, chi 2 test and binary logistic regression analysis. The prevalence rates of cigarette use and water pipe smoking were 25.9% and 23.3%, respectively. Cigarette smokers differed significantly from non-smokers on almost all of the assessed determinants. The I-Change model explained 85% of the total variance of cigarette smoking behavior. Cigarette smoking was determined by being male and older, having more depressive symptoms, having less Muslim identity, being more emancipated, perceiving more pros of smoking, having more modeling from peers and having lower self-efficacy. The popularity of cigarette use and water pipe smoking among Jordanian students necessitates health promotion interventions that motivate students not to engage in smoking behaviors by clearly outlining the outcomes of smoking and the healthier alternatives, how to cope with social influences and difficult situations in order to increase self-efficacy. PMID- 25141041 TI - Exposure to maternal smoking during fetal life affects food preferences in adulthood independent of the effects of intrauterine growth restriction. AB - Experimental animal studies have shown that nicotine exposure during gestation alters the expression of fetal hypothalamic neuropeptides involved in the control of appetite. We aimed to determine whether the exposure to maternal smoking during gestation in humans is associated with an altered feeding behavior of the adult offspring. A longitudinal prospective cohort study was conducted including all births from Ribeirao Preto (Sao Paulo, Brazil) between 1978 and 1979. At 24 years of age, a representative random sample was re-evaluated and divided into groups exposed (n = 424) or not (n = 1586) to maternal smoking during gestation. Feeding behavior was analyzed using a food frequency questionnaire. Covariance analysis was used for continuous data and the chi 2 test for categorical data. Results were adjusted for birth weight ratio, body mass index, gender, physical activity and smoking, as well as maternal and subjects' schooling. Individuals exposed to maternal smoking during gestation ate more carbohydrates than proteins (as per the carbohydrate-to-protein ratio) than non-exposed individuals. There were no differences in the consumption of the macronutrients themselves. We propose that this adverse fetal life event programs the individual's physiology and metabolism persistently, leading to an altered feeding behavior that could contribute to the development of chronic diseases in the long term. PMID- 25141042 TI - Maternal low-protein diet suppresses vascular and renal endothelial nitric oxide synthase phosphorylation in rat offspring independent of a postnatal fructose diet. AB - We investigated the effects of a postnatal fructose diet on the programmed hypertension and vascular and renal dysfunction in offspring from dams exposed to protein restriction. Pregnant Wistar rats were fed control and low-protein diets during the gestation and suckling periods. From the end of lactation, male offspring received standard chow or a 60% fructose diet: a control diet in the gestation and suckling periods and a control diet from the end of lactation, control-on-control (CC), 60% fructose diet-on-control (CF), control-on-low protein diet (LPC) and 60% fructose diet-on-low-protein diet (LPF). The systolic blood pressure (SBP) was measured during treatment. At postnatal days 94-101, urinary 24 h nitrate/nitrite (NO x ) content, protein levels of endothelial nitric oxide synthase (eNOS) and mRNA levels of endothelin-1 (ET-1), and NAD(P)H oxidase subunits in the aorta and kidney were examined. The SBP at postnatal days 97-101 increased in CF (137 +/- 2 mmHg, P < 0.05), LPC (135 +/- 1 mmHg, P < 0.05) and LPF (141 +/- 2 mmHg, P < 0.05), compared with CC (124 +/- 1 mmHg). The urinary NO x contents and eNOS phosphorylation in the aorta and kidney of CF, LPC and LPF decreased when compared with CC. In the aorta, the mRNA levels of NAD(P)H oxidase subunits p47phox in LPC and ET-1 in LPC and LPF increased. These results indicate that maternal protein restriction elevated the blood pressure, the downregulated nitric oxide production and eNOS phosphorylation, whereas the postnatal fructose diet made no significant difference to these alterations. PMID- 25141043 TI - Branched-chain amino acid supplemented diet during maternal food restriction prevents developmental hypertension in adult rat offspring. AB - Maternal food restriction is known to cause developmental hypertension in offspring. We have previously shown that maternal high-protein diet can reverse fetal programming of hypertension and that branched-chain amino acid (BCAA) concentrations in maternal and fetal plasma were increased by maternal high protein intake. Then, we hypothesized that isocaloric supplementation with BCAA to a maternal food restriction can reverse the adverse outcome. Pregnant rats were divided into four groups at 7.5 days postcoitum: normally nourished (NN) and 70% undernourished (UN) groups with and without BCAA supplementation (NN-standard diet (SD), NN-BCAA, UN-SD and UN-BCAA groups). Compared with pups in the NN groups, those in the UN-SD group had significantly increased systolic blood pressure (SBP) at 8 and 16 weeks of age (P < 0.05). However, the elevation of SBP was not observed in offspring in the UN-BCAA group. Offspring glomeruli number of the UN groups was significantly lower (P < 0.05) than that of the NN groups, independent of BCAA supplementation. Angiotensin II receptor type 2 (ATR2) mRNA and protein expression in the kidney was significantly augmented in the UN-BCAA group at 30 weeks of age. In conclusion, BCAA supplementation during maternal food restriction prevents developmental hypertension together with increased ATR2 expression in adult offspring kidney. PMID- 25141044 TI - Neonatal oxygen exposure leads to increased aortic wall stiffness in adult rats: a Doppler ultrasound study. AB - We have previously shown that neonatal high oxygen (O2) exposure in rats leads to hypertension and vascular dysfunction in adulthood. Pulse-wave velocity (PWV), an indirect measure of vascular biophysical properties (arterial stiffness or distensibility), is a sensitive marker of cardiovascular health. Its measurement in rats is mostly based on invasive hemodynamics measurements, prohibiting longitudinal studies particularly relevant in models of developmental programming of cardiovascular dysfunctions. With this study, we sought (1) to verify the feasibility and validity of measuring of aortic PWV in Sprague-Dawley rats by ultrasound; (2) to use the technique to compare aortic PWV in adult rats exposed to O2 as newborns (80% day 3-10 of life) v. controls; and (3) to develop an algorithm to calculate PWV in a non-invasive manner. We calculated aortic PWV using standard echocardiography and electrocardiogram, and validated the measures with PWV obtained by intraaortic catheters. Aortic full length was measured at sacrifice. PWV was significantly increased in O2 exposed (505 +/- 18 cm/s) v. control animals (421 +/- 17 cm/s, P < 0.01). With regard to weight, femur length and distance from the manubrium to the anal margin (MA length), the latter showed the best correlation (R = 0.84, P < 0.0001) with full aorta length derived from (L) = 0.339 * (MA length) + 4.281. The current data using echo-Doppler method demonstrated increased aortic stiffness in adult rats exposed to hyperoxia as newborns and suggests that non-invasive longitudinal studies of aortic PWV can be performed using the proposed algorithm for estimation of the full aorta length. PMID- 25141045 TI - Cultured neonatal rat cardiomyocytes display differences in glucose uptake and sensitivity to dexamethasone related to maternal diet. AB - Feeding a low protein (LP) diet in rat pregnancy is associated with impaired cardiovascular health and function, possibly as a result of tissue remodelling. To assess whether cardiomyocytes retain differences induced by protein restriction, cells from neonatal rats exposed to control or LP diets in utero were cultured for a period of 10 days. At the end of this period, no differences in cell size, proliferation differentiation or metabolic function were noted. When treated with dexamethasone (0.1-10 MUM) for 2 days, it was noted that insulin-stimulated glucose uptake was enhanced, but only in cells from LP rats. Increased glucocorticoid sensitivity of cardiomyocytes from LP rats could not be explained by differential expression of the glucocorticoid receptor or the glucose transporters, GLUT1 and GLUT4. The findings of the study suggest that sensitivity to endocrine signals may be permanently programmed by undernutrition through mechanisms that are preserved in vitro. PMID- 25141046 TI - Mechanistic investigation of the cleavage of phosphodiester catalyzed by a symmetrical oxyimine-based macrocyclic dinuclear zinc complex: a DFT study. AB - Density functional theory (DFT) was utilized to investigate the hydrolysis reaction mechanisms of phosphodiester BNPP (BNPP = bis(4-nitrophenyl)phosphate) catalyzed by a symmetrical oxyimine-based macrocyclic dinuclear zinc(ii) complex. We examined the nature of the nucleophilic reagent and the active form of the catalyst. The coordination and binding models of the catalyst-substrate complex were explored and we investigated two catalyst configurations (a ridge configuration and a plane configuration), four basic catalyst-substrate binding models (a mono-point-binding model, a dual-point-binding model, an OH-bridging model and a mono-center-dual-binding model) and two alternate roles for the metal coordinated hydroxide ion (whether it acts as a nucleophile or as a general base to facilitate the deprotonation of a solvent molecule). The one-point-binding mode was found to be preferred to construct a starting reactant. Nine plausible reaction mechanisms were proposed and investigated. Mechanism 1, a stepwise SN2 type addition-substitution reaction involving a para-position nucleophilic attack and the configuration inversion of the phosphate, was found to be the most favorable pathway. All of the proposed pathways are derived from alternate mechanisms such as a ping-pong mechanism and an AP mechanism. The ping-pong mechanism in combination with the role of the metal-coordinated hydroxide ion acting as a nucleophile was found to be more competitive than the other mechanisms examined. Results reported in this paper are consistent with, and can be utilized to systematically interpret, the experimental observations in the literature. PMID- 25141047 TI - Land snails as a diet diversification proxy during the early upper palaeolithic in Europe. AB - Despite the ubiquity of terrestrial gastropods in the Late Pleistocene and Holocene archaeological record, it is still unknown when and how this type of invertebrate resource was incorporated into human diets. In this paper, we report the oldest evidence of land snail exploitation as a food resource in Europe dated to 31.3-26.9 ka yr cal BP from the recently discovered site of Cova de la Barriada (eastern Iberian Peninsula). Mono-specific accumulations of large Iberus alonensis land snails (Ferussac 1821) were found in three different archaeological levels in association with combustion structures, along with lithic and faunal assemblages. Using a new analytical protocol based on taphonomic, microX-Ray Diffractometer (DXR) and biometric analyses, we investigated the patterns of selection, consumption and accumulation of land snails at the site. The results display a strong mono-specific gathering of adult individuals, most of them older than 55 weeks, which were roasted in ambers of pine and juniper under 375 degrees C. This case study uncovers new patterns of invertebrate exploitation during the Gravettian in southwestern Europe without known precedents in the Middle Palaeolithic nor the Aurignacian. In the Mediterranean context, such an early occurrence contrasts with the neighbouring areas of Morocco, France, Italy and the Balkans, where the systematic nutritional use of land snails appears approximately 10,000 years later during the Iberomaurisian and the Late Epigravettian. The appearance of this new subsistence activity in the eastern and southern regions of Spain was coeval to other demographically driven transformations in the archaeological record, suggesting different chronological patterns of resource intensification and diet broadening along the Upper Palaeolithic in the Mediterranean basin. PMID- 25141048 TI - [Cu]-catalyzed domino Sonogashira coupling followed by intramolecular 5-exo-dig cyclization: synthesis of 1,3-dihydro-2-benzofurans. AB - An efficient [Cu]-catalyzed domino Sonogashira coupling of o-bromobenzyl tertiary alcohols with terminal aryl acetylenes followed by an intramolecular anti-5-exo dig cyclization is presented. The terminal aryl acetylenes were identified as ideal coupling partners that permit in situ intramolecular oxacyclization by the hydroxyl group as a pre-existing nucleophile of the alcohol. Notably, the intramolecular nucleophilic attack of the hydroxyl group took place on the alkyne moiety in a highly regio- and stereoselective manner. Interestingly, this method was amenable to a wide variety of o-bromobenzyl tertiary alcohols and furnished the corresponding cyclic ethers. On the other hand, when terminal alkyl acetylenes were used as the coupling partners, the reaction was impeded after the Sonogashira coupling. PMID- 25141050 TI - Investigating the genetics of seizure-prone flies. PMID- 25141051 TI - Negative pressure limits traumatic brain damage. PMID- 25141053 TI - Tiny fly ears inspire a new hearing device. PMID- 25141054 TI - Dopamine pathway induces emergence from anesthesia. PMID- 25141056 TI - The autonomous arms of the octopus. PMID- 25141057 TI - Response to Protocol Review Scenario: Compliance and communication. PMID- 25141058 TI - Response to Protocol Review Scenario: IACUC is responsible. PMID- 25141059 TI - Setting timelines to correct deficiencies. PMID- 25141060 TI - Response to Protocol Review Scenario: Cooperation and IACUC approval. PMID- 25141062 TI - Evaluation of ultrasonic vocalizations in common marmosets (Callithrix jacchus) as a potential indicator of welfare. AB - The vocal repertoire in common marmosets (Callithrix jacchus) has been assumed to consist not only of vocalizations audible to humans but also of ultrasonic vocalizations (USVs). The use of USVs to socially indicate distress has not been evaluated in this species, however. The authors analyzed the ultrasonic vocal repertoire of the common marmoset under normal housing conditions, under various experimental manipulations intended to elicit positive or negative emotional responses and during stressful experiences including blood draw and exposure to a perceived predator. Analysis of the recordings showed that marmosets produced vocalizations with ultrasonic components as part of their normal vocal repertoire, but these vocalizations all have audible components as well. Only 4 of the 13 types of vocalizations had ultrasonic components. These ultrasonic components were not reliably associated with responses to different experimental manipulations, suggesting that they are not used to indicate pain, discomfort or distress. PMID- 25141063 TI - An animal tracking system for behavior analysis using radio frequency identification. AB - Evaluating the behavior of mice and rats has substantially contributed to the progress of research in many scientific fields. Researchers commonly observe recorded video of animal behavior and manually record their observations for later analysis, but this approach has several limitations. The authors developed an automated system for tracking and analyzing the behavior of rodents that is based on radio frequency identification (RFID) in an ultra-high-frequency bandwidth. They provide an overview of the system's hardware and software components as well as describe their technique for surgically implanting passive RFID tags in mice. Finally, the authors present the findings of two validation studies to compare the accuracy of the RFID system versus commonly used approaches for evaluating the locomotor activity and object exploration of mice. PMID- 25141064 TI - My training as an IACUC community member. PMID- 25141065 TI - Don't get no respect. PMID- 25141066 TI - Making great animal friends. PMID- 25141067 TI - Nitrogen-doped graphdiyne as a metal-free catalyst for high-performance oxygen reduction reactions. AB - Fuel cells and metal-air batteries will only become widely available in everyday life when the expensive platinum-based electrocatalysts used for the oxygen reduction reactions are replaced by other efficient, low-cost and stable catalysts. We report here the use of nitrogen-doped graphdiyne as a metal-free electrode with a comparable electrocatalytic activity to commercial Pt/C catalysts for the oxygen reduction reaction in alkaline fuel cells. Nitrogen doped graphdiyne has a better stability and increased tolerance to the cross-over effect than conventional Pt/C catalysts. PMID- 25141068 TI - Percutaneous treatment of biliary complications in pediatric patients after liver transplantation. AB - PURPOSE: Evaluation of the efficiency and safety of the percutaneous treatment of biliary complications in pediatric liver transplant recipients. METHODS: We conducted a retrospective analysis of children who underwent biliary percutaneous interventions after pediatric liver transplantation (PLT) over a 4-year period. Kind of biliary complication, interval between liver transplantation and intervention, status of the vessels, procedural interventional management, technical and clinical success, course of cholestasis, PTBD-related complications and patient survival were analyzed. RESULTS: 23 percutaneous transhepatic biliary drainages (PTBD) were placed in 16 children due to 18 biliary complications. The drains were customized individually by shortening and cutting additional holes. PTBD placement was performed with technical and clinical success in all children. 4 children received PTBD to bridge the time to retransplantation and surgical revision. One child received PTBD for successful treatment of anastomotic leakage. Long-term dilation of biliary stenoses was performed in 13 children using PTBD. One of these 13 patients showed recurrent stenosis during a median follow-up of 295 days. Bilirubin values decreased significantly after PTBD placement for biliary stenosis. One patient suffered from bacteremia after PTBD replacement. CONCLUSION: PTBD treatment for biliary complications after PLT is effective and safe. PMID- 25141069 TI - Sugar-based amphiphilic polymers for biomedical applications: from nanocarriers to therapeutics. AB - Various therapeutics exhibit unfavorable physicochemical properties or stability issues that reduce their in vivo efficacy. Therefore, carriers able to overcome such challenges and deliver therapeutics to specific in vivo target sites are critically needed. For instance, anticancer drugs are hydrophobic and require carriers to solubilize them in aqueous environments, and gene-based therapies (e.g., siRNA or pDNA) require carriers to protect the anionic genes from enzymatic degradation during systemic circulation. Polymeric micelles, which are self-assemblies of amphiphilic polymers (APs), constitute one delivery vehicle class that has been investigated for many biomedical applications. Having a hydrophobic core and a hydrophilic shell, polymeric micelles have been used as drug carriers. While traditional APs are typically comprised of nondegradable block copolymers, sugar-based amphiphilic polymers (SBAPs) synthesized by us are comprised of branched, sugar-based hydrophobic segments and a hydrophilic poly(ethylene glycol) chain. Similar to many amphiphilic polymers, SBAPs self assemble into polymeric micelles. These nanoscale micelles have extremely low critical micelle concentrations offering stability against dilution, which occurs with systemic administration. In this Account, we illustrate applications of SBAPs for anticancer drug delivery via physical encapsulation within SBAP micelles and chemical conjugation to form SBAP prodrugs capable of micellization. Additionally, we show that SBAPs are excellent at stabilizing liposomal delivery systems. These SBAP-lipid complexes were developed to deliver hydrophobic anticancer therapeutics, achieving preferential uptake in cancer cells over normal cells. Furthermore, these complexes can be designed to electrostatically complex with gene therapies capable of transfection. Aside from serving as a nanocarrier, SBAPs have also demonstrated unique bioactivity in managing atherosclerosis, a major cause of cardiovascular disease. The atherosclerotic cascade is usually triggered by the unregulated uptake of oxidized low-density lipoprotein, a cholesterol carrier, in macrophages of the blood vessel wall; SBAPs can significantly inhibit oxidized low-density lipoprotein uptake in macrophages and abrogate the atherosclerotic cascade. By modification of various functionalities (e.g., branching, stereochemistry, hydrophobicity, and charge) in the SBAP chemical structure, SBAP bioactivity was optimized, and influential structural components were identified. Despite the potential of SBAPs as atherosclerotic therapies, blood stability of the SBAP micelles was not ideal for in vivo applications, and means to stabilize them were pursued. Using kinetic entrapment via flash nanoprecipitation, SBAPs were formulated into nanoparticles with a hydrophobic solute core and SBAP shell. SBAP nanoparticles exhibited excellent physiological stability and enhanced bioactivity compared with SBAP micelles. Further, this method enables encapsulation of additional hydrophobic drugs (e.g., vitamin E) to yield a stable formulation that releases two bioactives. Both as nanoscale carriers and as polymer therapeutics, SBAPs are promising biomaterials for medical applications. PMID- 25141070 TI - Neurological recovery and antioxidant effects of curcumin for spinal cord injury in the rat: a network meta-analysis and systematic review. AB - Spinal cord injury (SCI) is a devastating condition affecting young, healthy individuals worldwide. Existing agents have inadequate therapeutic efficacy, and some are associated with side effects. Our objective is to summarize and critically assess the neurological recovery and antioxidant effects of curcumin for treatment of SCI in rat models. PubMed, Embase, and Chinese databases were searched from their inception date to February 2014. Two reviewers independently selected animal studies that evaluated neurological recovery and antioxidant effects of curcumin, compared to placebo, in rats with SCI, extracted data, and assessed the methodological quality. A pair-wise analysis and a network meta analysis were performed. Eight studies with adequate randomization were selected and included in the systematic review. Two studies had a higher methodological quality. Overall, curcumin appears to significantly improve neurological function, as assessed using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale (four studies, n=132; pooled mean difference [MD]=3.09; 95% confidence interval [CI], 3.40-4.45; p=0.04), in a random-effects model and decrease malondialdehyde (MDA) using a fixed-effects model (four studies, n=56; pooled MD= 1.00; 95% CI=-1.59 to -0.42; p=0.00008). Effect size, assessed using the BBB scale, increased gradually with increasing curcumin dosage. The difference between low- and high-dose curcumin using the BBB scale was statistically significant. Neurological recovery and antioxidant effects of curcumin were observed in rats with SCI despite poor study methodological quality. PMID- 25141071 TI - Budesonide for maintenance of remission in Crohn's disease. AB - BACKGROUND: Corticosteroids are effective for induction, but not maintenance of remission in Crohn's disease. Significant concerns exist regarding the risk for adverse events, particularly when corticosteroids are used for long treatment courses. Budesonide is a glucocorticoid with limited systemic bioavailability due to extensive first-pass hepatic metabolism and is effective for induction of remission in Crohn's disease. OBJECTIVES: To evaluate the efficacy and safety of oral budesonide for maintenance of remission in Crohn's disease. SEARCH METHODS: The following databases were searched from inception to 12 June 2014: PubMed, MEDLINE, EMBASE, CENTRAL, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched. SELECTION CRITERIA: Randomized controlled trials comparing budesonide to a control treatment, or comparing two doses of budesonide, were included. The study population included patients of any age with quiescent Crohn's disease. DATA COLLECTION AND ANALYSIS: Two independent investigators reviewed studies for eligibility, extracted data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was maintenance of remission at various reported follow-up times during the study. Secondary outcomes included: time to relapse, mean change in CDAI, clinical, histological, improvement in quality of life, adverse events and study withdrawal. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference (MD) and 95% CI for continuous outcomes. Data were analysed on an intention-to-treat basis. The Chi(2) and I(2) statistics were used to assess heterogeneity. Random-effects models were used to allow for expected clinical and statistical heterogeneity. The overall quality of the evidence supporting the primary outcome was assessed using the GRADE criteria. MAIN RESULTS: Twelve studies (n = 1273 patients) were included in the review: eight studies compared budesonide to placebo, one compared budesonide to 5-aminosalicylates, one compared budesonide to traditional systemic corticosteroids, one compared budesonide to azathioprine, and one compared two doses of budesonide. Nine studies used a controlled ileal release form of budesonide, while three used a pH-modified release formulation. Nine studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to blinding and one of these studies also had inadequate allocation concealment. Budesonide 6 mg daily was no more effective than placebo for maintenance of remission at 3 months, 6 months or 12 months. At three months 64% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.25, 95% CI 1.00 to 1.58; 6 studies, 540 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to moderate heterogeneity (I(2) = 56%) and sparse data (315 events). At six months 61% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.15, 95% CI 0.95 to 1.39; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (238 events). At 12 months 55% of budesonide 6 mg patients remained in remission compared to 48% of placebo patients (RR 1.13; 95% CI 0.94 to 1.35; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (215 events). Similarly, there was no significant benefit for budesonide 3 mg compared to placebo at 6 and 12 months. There was no statistically significant difference in continued remission at 12 months between budesonide and weaning doses of prednisolone (RR 0.79; 95% CI 0.55 to 1.13; 1 study, 90 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (51 events) and high risk of bias (no blinding). Budesonide 6 mg was better than mesalamine 3 g/day at 12 months (RR 2.51, 95% CI 1.03 to 6.12; 1 study, 57 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to very sparse data (18 events) and high risk of bias (no blinding). There was no statistically significant difference in continued remission at 12 months between budesonide and azathioprine (RR 0.81; 95% CI 0.61 to 1.08; 1 study 77 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to sparse data (55 events) and high risk of bias (single-blind and no allocation concealment). The use of budesonide 6 mg resulted in slight improvements in CDAI scores when assessed at 6 months (MD 24.30, 95% CI -46.31 to -2.29) and 12 months (MD -23.49, 95% CI -46.65 to -0.32) and mean time to relapse of disease (MD 59.93 days, 95% CI 19.02 to 100.84). Mean time to relapse was significantly shorter for patients receiving budesonide than for those receiving azathioprine (MD -58.00, 95% CI -96.68 to -19.32). Adverse events were not more common in patients treated with budesonide compared to placebo (6 mg: RR 1.51, 95% CI 0.90 to 2.52; 3 mg: RR 1.19, 95% CI 0.63 to 2.24). These events were relatively minor and did not result in increased rates of study withdrawal. Commonly reported treatment-related adverse effects included acne, moon facies, hirsutism, mood swings, insomnia, weight gain, striae, and hair loss. Abnormal adrenocorticoid stimulation tests were seen more frequently in patients receiving both 6 mg (RR 2.88, 95% CI 1.72 to 4.82) and 3 mg daily (RR 2.73, 95% CI 1.34 to 5.57) compared to placebo. AUTHORS' CONCLUSIONS: These data suggest budesonide is not effective for maintenance of remission in CD, particularly when used beyond three months following induction of remission. Budesonide does have minor benefits in terms of lower CDAI scores and longer time to relapse of disease. However, these benefits are offset by higher treatment related adverse event rates and more frequent adrenocorticoid suppression in patients receiving budesonide. PMID- 25141072 TI - Management of haemangiopericytoma located in the spinal cord diagnosed during pregnancy. PMID- 25141073 TI - Could point-of-care testing be effective for reducing the prevalence of trichomoniasis in remote Aboriginal communities? AB - High prevalence of trichomoniasis is reported for many remote Indigenous communities despite intensive screening and treatment programs. Mathematical modelling has previously been used to show that point-of-care (POC) testing for gonorrhoea and chlamydia has the potential to increase the impact of screening in reducing the prevalence of these sexually transmissible infections. The study was extended to estimate the impact of a rapid POC test for trichomoniasis. The results suggest that POC testing in place of conventional testing will also provide additional reductions in trichomoniasis prevalence. However, more emphasis should be placed on testing for trichomoniasis in older women due to the high prevalence observed in this group. PMID- 25141074 TI - Using Nonechoplanar Diffusion-weighted MRI to Assess Treatment Response in Active Graves Orbitopathy: A Novel Approach with 2 Case Reports. AB - Two patients (68 and 71 years, both female) with sight threatening, active Graves orbitopathy but low clinical activity score underwent MRI scans before and after intravenous corticosteroid treatment. Two MRI techniques, short-term inversion recovery and nonechoplanar diffusion-weighted imaging, were used. Apparent diffusion coefficient values reduced in patient 1 who had successful medical treatment and remained elevated in patient 2 who had an inadequate treatment response. Nonechoplanar diffusion-weighted imaging provided a quantitative measure of treatment response by calculation of the apparent diffusion coefficient. The novel use of nonechoplanar diffusion-weighted imaging for monitoring treatment response in Graves orbitopathy is illustrated but requires further validation. PMID- 25141075 TI - On the directionality and non-linearity of halogen and hydrogen bonds. AB - Benchmark quality structures and interaction energies have been produced using explicitly correlated coupled cluster methods for a systematic series of hydrogen and halogen bonded complexes: B...HCCH, B...HCl and B...ClF, with six different Lewis bases B. Excellent agreement with experimental structures is observed, verifying the method used to deduce the equilibrium deviation from collinearity of the intermolecular bond via rotational spectroscopy. This level of agreement also suggests that the chosen theoretical method can be employed when experimental equilibrium data are not available. The application of symmetry adapted perturbation theory reveals differences in the underlying mechanisms of interaction for hydrogen and halogen bonding, providing insights into the differences in non-linearity. In the halogen bonding case it is shown that the dispersion term is approximately equal to the overall interaction energy, highlighting the importance of choosing the correct theoretical method for this type of interaction. PMID- 25141076 TI - RandomForest4Life: a Random Forest for predicting ALS disease progression. AB - We describe a method for predicting disease progression in amyotrophic lateral sclerosis (ALS) patients. The method was developed as a submission to the DREAM Phil Bowen ALS Prediction Prize4Life Challenge of summer 2012. Based on repeated patient examinations over a three- month period, we used a random forest algorithm to predict future disease progression. The procedure was set up and internally evaluated using data from 1197 ALS patients. External validation by an expert jury was based on undisclosed information of an additional 625 patients; all patient data were obtained from the PRO-ACT database. In terms of prediction accuracy, the approach described here ranked third best. Our interpretation of the prediction model confirmed previous reports suggesting that past disease progression is a strong predictor of future disease progression measured on the ALS functional rating scale (ALSFRS). We also found that larger variability in initial ALSFRS scores is linked to faster future disease progression. The results reported here furthermore suggested that approaches taking the multidimensionality of the ALSFRS into account promise some potential for improved ALS disease prediction. PMID- 25141077 TI - A hybrid polyoxometalate-organic molecular catalyst for visible light driven water oxidation. AB - A novel organic-inorganic hybrid monocapped/bicapped Keggin structure [Co(II)(bpy)3]6(H2bpy)[(Co(II)bpy)2(PMo8(VI)Mo4(V)O40)]3 [(Co(II)bpy)(PMo8(VI)Mo4(V)O40)].16H2O (bpy = 2,2'-bipyridine) was synthesized and shown to be an efficient visible light-driven catalyst for water oxidation. PMID- 25141078 TI - Assessing impact of physical activity-based youth development programs: validation of the Life Skills Transfer Survey (LSTS). AB - PURPOSE: A signature characteristic of positive youth development (PYD) programs is the opportunity to develop life skills, such as social, behavioral, and moral competencies, that can be generalized to domains beyond the immediate activity. Although context-specific instruments are available to assess developmental outcomes, a measure of life skills transfer would enable evaluation of PYD programs in successfully teaching skills that youth report using in other domains. The purpose of our studies was to develop and validate a measure of perceived life skills transfer, based on data collected with The First Tee, a physical activity-based PYD program. METHOD: In 3 studies, we conducted a series of steps to provide content and construct validity and internal consistency reliability for the Life Skills Transfer Survey (LSTS), a measure of perceived life skills transfer. RESULTS: Study 1 provided content validity for the LSTS that included 8 life skills and 50 items. Study 2 revealed construct validity (structural validity) through a confirmatory factor analysis and convergent validity by correlating scores on the LSTS with scores on an assessment tool that measures a related construct. Study 3 offered additional construct validity by reassessing youth 1 year later and showing that scores during both time periods were invariant in factor pattern, loadings, and variances and covariances. Studies 2 and 3 demonstrated internal consistency reliability of the LSTS. CONCLUSION: RESULTS from 3 studies provide evidence of content and construct validity and internal consistency reliability for the LSTS, which can be used in evaluation research with youth development programs. PMID- 25141079 TI - Music is not our enemy, but noise should be regulated: thoughts on shooting/conflicts related to Dama square dance in China. AB - While Dama square dance is gaining popularity in China, especially with middle aged and older-adult women-hence the "Dama" (Chinese for "big mamas") moniker there have been conflicts due to the loud music played for the activity. After a brief explanation of Dama square dance and a description of the context of the conflicts, this commentary shares some thoughts on the issues raised, reviews the negative impact and regulation of noise, and calls for creating more public green space in Chinese cities and for developing a new music delivery system that could eliminate public music noise for group physical activities. PMID- 25141080 TI - Teacher effectiveness in physical education-consensus? AB - This article synthesizes the series of manuscripts on teacher effectiveness in physical education recently published by the Research Quarterly for Exercise and Sport and highlights both the consensus and points of disagreement. Although there is much agreement as to the mission to develop a physically active lifestyle, there is a great deal of disagreement on how to get there, which makes the task of measuring effectiveness difficult. The current reform effort in education to measure teacher effectiveness makes it essential that professionals in physical education at all levels be participants in this process. PMID- 25141081 TI - The pill not taken: revisiting Physical Education Teacher Effectiveness in a Public Health Context. AB - In "Physical Education Teacher Effectiveness in a Public Health Context," we took a broad view of physical education (PE) teacher effectiveness that included public health need and support for PE. Public health officials have been consistent and fervent in their support of PE, and for more than two decades, they have called on schools to promote and provide physical activity. They have strongly recommended PE because: (a) It is part of the formalized school curriculum and an essential access point to provide and promote physical activity for nearly all children, and (b) it is the only venue where the least active children experience physical activity at higher intensities. Within the current marginalized status of PE, public health is an ally. Hence, we took a broad public health position, indicated that teacher effectiveness is tied closely to PE program effectiveness, identified physical activity and its assessment as important parts of PE, offered a vision of teacher effectiveness that goes beyond the PE lesson to include components of the comprehensive school physical activity model, and emphasized the need for the collection of data to support PE and physical activity programs. We have read the written reviews and listened to dialogue about our article. In this follow-up article, we address the major comments using 4 themes: prioritizing public health over other PE emphases, PE having a muddled mission, concerns about physical activity, and extending the roles and skills of physical educators. PMID- 25141082 TI - A response to the conversations on effective teaching in physical education. AB - In this response to articles on effective teaching in physical education that have been published in Research Quarterly for Exercise and Sport, I thank the authors of these articles for the thoughtfulness of their comments and the respondents for their comments on my own article. I elaborate on my position and discuss a number of issues raised by these authors. My central thesis is that meeting the state standards for physical education is not only the best way to advocate for our field, but it is a moral imperative-moral because children and youth deserve a quality physical education and this should not be left to chance, and imperative because, as the authors of the articles on this topic have argued, this is a critical time to be counted as a subject matter. I conclude by thanking the editor in chief for providing the forum to discuss these important issues. PMID- 25141083 TI - Top 10 research questions related to exercise deficit disorder (EDD) in youth. AB - Exercise deficit disorder (EDD) is a pediatric medical condition characterized by reduced levels of moderate-to-vigorous physical activity (MVPA) that are below current recommendations and inconsistent with positive health outcomes. At present, a majority of children and adolescents meet the diagnostic criteria for EDD because they are not accumulating minimum thresholds of daily MVPA. The purpose of this article is to highlight 10 important research questions related to EDD in youth. The critical research needs to better define the clinical spectrum of EDD to include an assessment of physical activity behaviors to determine the age or stage of maturation at which EDD first emerges; an examination of the kinesiogenesis of movement skills and physical abilities; and an evaluation of lifestyle factors that can influence the MVPA trajectory in youth. Research questions about interventions and policies to treat EDD include evaluating the education and training of health care providers on the importance of exercise medicine; determining the effectiveness of strategies to identify and treat youth with EDD in clinical practice; developing sensitive, specific, and cost-effective methods to diagnose youth with EDD; and assessing methods to promote health care reimbursement for the treatment of this condition. Without future research to optimize identification, treatment, and management strategies for youth with EDD, new health care concerns with significant biomedical, psychosocial, economic, and political ramifications will continue to emerge. PMID- 25141084 TI - Effects of mental and physical practice on a finger opposition task among children. AB - PURPOSE: We sought to compare the effects of physical practice (PP) and mental practice (MP) on the immediate and long-term learning of the finger-to-thumb opposition sequence task (FOS) in children; in addition, we investigated the transfer of this learning to an untrained sequence of movements and to the contralateral untrained hand. METHOD: This study included thirty-six 9- and 10 year-old children who were randomly allocated into 3 groups: MP, PP, and no practice (NP). The MP and PP groups were subjected to a single session of training with the dominant trained hand. MP participants were trained by mentally rehearsing the movements, PP participants were trained by executing the movements, and the NP group had no training. The performance of the trained sequence (TS) and untrained reverse sequence (URS) by each of the 3 groups was evaluated under identical conditions before training, after 5 min, and at 4 days, 7 days, and 28 days after training. RESULTS: Whereas both trained groups (MP and PP) showed statistically significant improvement in TS using the trained hand at all assessment points after the training, only MP participants were able to transfer the performance gains from the TS to the URS and from the trained hand to the untrained opposite hand. CONCLUSION: Children were able to learn the FOS through MP or PP with a similar level of performance. Unlike PP, MP allowed for the transfer of performance gain to the URS and to the opposite hand, suggesting that the internal representations developed by MP were effector-independent. PMID- 25141085 TI - Modified Delphi investigation of motor development and learning in physical education teacher education. AB - PURPOSE: As the scope of motor development and learning knowledge has successfully broadened over the years, there is an increased need to identify the content and learning experiences that are essential in preparing preservice physical educators. The purpose of this study was to generate expert consensus regarding the most critical motor development and learning competencies that prospective physical educators need to learn within the physical education teacher education (PETE) curriculum and to identify learning environments and instructional methods for delivering core knowledge. METHOD: The study employed a 2-round, modified Delphi procedure involving the repeated circulation of a questionnaire to a panel of motor development specialists, motor learning specialists, teacher educators, and K-12 physical education teachers. Panel members rated an initial list of theoretical and applied motor development and learning competencies derived from various curricular guidelines and textbook sources. An open-response question was incorporated into the 2nd round asking panel members to recommend specific instructional methods and settings for delivering core motor development and learning content to prospective physical educators within the PETE curriculum. RESULTS: Expert consensus determined that 64 out of the initial 159 motor development and learning competencies were critical in preparing preservice physical educators. Early field experiences and peer practice in a variety of settings were recommended by panelists for delivering the identified competencies. CONCLUSIONS: The Discussion section represents an important link between the motor development and learning body of knowledge and physical education teachers' role in promoting skillful movement, physical activity, and fitness among youth in the school setting. PMID- 25141086 TI - Differences of ballet turns (pirouette) performance between experienced and novice ballet dancers. AB - PURPOSE: This study investigated the different postural control strategies exhibited by experienced and novice dancers in ballet turns (pirouettes). METHOD: Thirteen novice and 13 experienced dancers performed ballet turns with dominant leg support. The peak push force was measured in the double-leg support phase. The inclination angles of rotation axis with respect to vertical axis were calculated in the early single-leg support phase as well as the initiation sequence of ankle, knee, and hip joints on the supporting leg. Moreover, the anchoring index of the head was computed in the transverse plane during turning. RESULTS: The novice dancers applied a greater push force, an increased inclination angle of rotation axis, and an insufficient proximal-to-distal extension sequence pattern. The novice dancers also had a smaller head-anchoring index compared with experienced dancers, which meant novice dancers were not using a space target as a stability reference. CONCLUSIONS: A poorer performance in novice dancers could result from higher push force in propulsion, lack of a "proximal-to-distal extension sequence" pattern, and lack of visual spotting for postural stability. Training on sequential initiation of lower-extremity joints and rehearsal of visual spotting are essential for novice dancers to obtain better performance on ballet turns. PMID- 25141087 TI - The hot hand belief and framing effects. AB - PURPOSE: Recent evidence of the hot hand in sport-where success breeds success in a positive recency of successful shots, for instance-indicates that this pattern does not actually exist. Yet the belief persists. We used 2 studies to explore the effects of framing on the hot hand belief in sport. We looked at the effect of sport experience and task on the perception of baseball pitch behavior as well as the hot hand belief and free-throw behavior in basketball. METHOD: Study 1 asked participants to designate outcomes with different alternation rates as the result of baseball pitches or coin tosses. Study 2 examined basketball free-throw behavior and measured predicted success before each shot as well as general belief in the hot hand pattern. RESULTS: The results of Study 1 illustrate that experience and stimulus alternation rates influence the perception of chance in human performance tasks. Study 2 shows that physically performing an act and making judgments are related. Specifically, beliefs were related to overall performance, with more successful shooters showing greater belief in the hot hand and greater predicted success for upcoming shots. CONCLUSIONS: Both of these studies highlight that the hot hand belief is influenced by framing, which leads to instability and situational contingencies. We show the specific effects of framing using accumulated experience of the individual with the sport and knowledge of its structure and specific experience with sport actions (basketball shots) prior to judgments. PMID- 25141088 TI - Describing strategies used by elite, intermediate, and novice ice hockey referees. AB - Much is known about sport officials' decisions (e.g., anticipation, visual search, and prior experience). Comprehension of the entire decision process, however, requires an ecologically valid examination. To address this, we implemented a 2-part study using an expertise paradigm with ice hockey referees. PURPOSE: Study 1 explored the strategies referees indicated they used to make decisions. For Study 2, we sought to confirm the emergent codes of Study 1 and further examine referee expertise and evaluations of decision making. METHOD: In Study 1, 2 elite, 2 intermediate, and 2 novice referees wore helmet cameras for 1 game and participated in stimulated recall interviews, which were coded using theoretical and focused codes. Study 2 involved focus groups that each watched and commented on 2 helmet camera videotapes from Study 1; 1 videotape consisted of an elite referee's game and the other included an intermediate referee's game. The focus-group data were analyzed using the same coding structure from Study 1. RESULTS: Combined, 3 distinct theoretical codes were identified: (a) primary referee strategies, (b) secondary referee strategies, and (c) cognitive and situational influences on refereeing. Study 1 showed that elite referees demonstrated more sophisticated knowledge of the 3 theoretical codes. In Study 2, elite referees demonstrated enhanced declarative knowledge compared with intermediate and novice participants. CONCLUSIONS: Elite referees have more elaborate knowledge bases than do nonelite referees. In the discussion, we explain our results and link them with the action plan profiles framework. PMID- 25141089 TI - Impact of overt and subclinical hypothyroidism on exercise tolerance: a systematic review. AB - PURPOSE: This systematic review describes the state of the art of the impact of hypothyroidism on exercise tolerance and physical performance capacity in untreated and treated patients with hypothyroidism. METHOD: A systematic computer aided search was conducted using biomedical databases. Relevant studies in English, German, and Dutch, published from the earliest date of each database up to December 2012, were identified. RESULTS: Out of 116 studies, a total of 38 studies with 1,379 patients fulfilled the inclusion criteria. These studies emphasize the multifactorial causes of exercise intolerance in untreated patients by the impact of limitations in different functional systems, with cardiovascular, cardiopulmonary, musculoskeletal, neuromuscular, and cellular metabolic systems acting in concert. Moreover, the studies affirm that exercise intolerance in patients is not always reversible during adequate hormone replacement therapy. As a consequence, despite a defined euthyroid status, there remains a significant group of treated patients with persistent complaints related to exercise intolerance who are suffering from limitations in daily and sport activities, as well as an impaired quality of life. An explanation for this phenomenon is lacking. Only 2 studies investigated the effects of a physical training program, and they showed inconsistent effects on the performance capacity in untreated patients with subclinical hypothyroidism. CONCLUSIONS: A limited body of knowledge exists concerning exercise tolerance in treated patients with hypothyroidism, and there is an insufficient amount of quantitative studies on the effects of a physical training program. To enhance exercise and sports participation for this specific group, more research in this forgotten area is warranted. PMID- 25141090 TI - Association between accelerometer-assessed physical activity and objectively measured hearing sensitivity among U.S. adults with diabetes. AB - PURPOSE: The purpose of this study was to examine the association between objectively measured physical activity and hearing sensitivity among a nationally representative sample of U.S. adults with diabetes. METHOD: Data from the 2003 2006 National Health and Nutrition Examination Survey were used. One hundred eighty-four U.S. adults with diabetes wore an ActiGraph 7164 accelerometer and had their hearing function objectively assessed. A negative binomial logistic regression was used to examine the association between moderate-to-vigorous physical activity (MVPA) and hearing sensitivity. RESULTS were adjusted for age, gender, race/ethnicity, education, body mass index, comorbidity index, marital status, cotinine, homocysteine, high-density lipoprotein cholesterol, glycohemoglobin (HbA1c), C-reactive protein, microalbuminuria, noise exposure, and vision impairment. RESULTS: Compared to those with hearing within normal limits, results showed that participants with mild hearing loss and moderate or greater hearing loss, respectively, engaged in 93% fewer minutes of MVPA (incident rate ratio = 0.07; 95% CI [0.01, 0.60]) and 94% fewer minutes of MVPA (incident rate ratio = 0.06; 95% CI [0.01, 0.54]). CONCLUSION: Adults with diabetes who have greater hearing impairment are less physically active. Future research is needed to determine the direction of causality. PMID- 25141091 TI - Sixth-grade physical education: an acculturation of bullying and fear. AB - PURPOSE: Although bullying is recognized as a serious problem among adolescents, more information is needed regarding bullying within the context of physical education. Grounded in a social-ecological framework, the purpose of this investigation was to discover the perceptions students and teachers have about bullying in physical education and about peer and adult support. METHOD: Data collection included formal and informal interviews with 24 students and 4 teachers and 20 observations of 6th-grade physical education classes in 1 Midwestern school. Data were analyzed using a constant-comparative process. RESULTS: The results indicate that adults acculturate students to support a bullying climate by providing mixed information regarding social interactions, ignoring nonphysical instances of bullying, and promoting inappropriate curricular selections. Participants also report that perceived differences such as appearance, body size, physical ability, and personal attire ignite most episodes of harassment in physical education. Further, students perceive that fear prevents many from (a) reporting instances of bullying to those in authority, (b) assisting bullied friends, and (c) feeling safe in certain physical education locations. Finally, students and teachers report that bullying impacts students' desire to participate in physical education. CONCLUSIONS: Overall, evidence from this investigation suggests that an efficacious support system does not exist for addressing the magnitude of the bullying problem. Although this study provided an initial step toward understanding the social ecological factors affecting peer harassment in physical education, additional research is warranted. PMID- 25141092 TI - White blood cell counts mediate the effects of physical activity on prostate specific antigen levels. AB - PURPOSE: The purpose of this study was to examine whether white blood cell (WBC) level mediated the relationship between physical activity and prostate-specific antigen (PSA) levels. METHOD: Data from the 2003-2006 National Health and Nutrition Examination Survey were used; 1,726 U.S. adult men (aged 40 years or older) provided complete data on the study variables. Participants wore an ActiGraph 7164 accelerometer for a 7-day period to measure their physical activity behavior, and PSA and WBC levels were obtained from a blood sample. RESULTS: After adjustments, results showed that moderate-to-vigorous physical activity (MVPA) was inversely associated with WBC count (b = - .03; 95% CI [ - 0.04, - 0.006; p = .01), and WBC count (b = .10; 95% CI [0.009, 0.18; p = .04) was positively associated with PSA. Both the Sobel (coef. = - .004, SE = .002; z = - 2.0; p = .03) and the Aroian (coef. = - .004, SE = .002; z = - 1.9; p = .03) tests demonstrated that WBC mediated the relationship between physical activity and PSA. Additionally, among 107 participants with prostate cancer, survivors engaging in more MVPA had lower levels of WBC (b = - .04; 95% CI [ - 0.09, - 0.0009; p = .04). Conclusion Physical activity may influence PSA levels through WBC modulation; however, future research is needed to determine the direction of causality. Additionally, prostate cancer survivors engaging in higher levels of MVPA had lower levels of WBC, underscoring the importance of promoting physical activity among prostate cancer survivors. PMID- 25141093 TI - JROTC as a substitute for PE: really? AB - PURPOSE: Even though physical education (PE) is an evidence-based strategy for providing and promoting physical activity, alternative programs such as the Junior Reserve Officer Training Corps (JROTC) are commonly substituted for PE in many states. The purpose of this study was to compare student physical activity and lesson contexts during high school PE and JROTC sessions. METHOD: The System for Observing Fitness Instruction Time was used to assess PE and JROTC sessions (N = 38 each) in 4 high schools that provided both programs. Data were analyzed using t tests, negative binomial regression, and logistic regression. RESULTS: Students engaged in significantly more moderate-to-vigorous physical activity during PE than during JROTC sessions and they were significantly less sedentary. Significant differences between the 2 program types were also found among lesson contexts. CONCLUSIONS: PE and JROTC provide substantially different content and contexts, and students in these programs engage in substantially different amounts of moderate-to-vigorous physical activity. Students in JROTC, and perhaps other alternative programs, are less likely to accrue health-supporting physical activity and engage in fewer opportunities to be physically fit and motorically skilled. Policies and practices for providing substitutions for PE should be carefully examined. PMID- 25141094 TI - Publicizing female athletes' weights: implications for female psychology undergraduates acting as spectators. AB - PURPOSE: The purpose of this study was to examine the effects of including female athletes' weights in athletic event programs on female spectators' body image, eating disorder symptoms, self-esteem, and affective state and to investigate whether the magnitude of the athletes' reported weights had differential effects on female spectators (i.e., do female spectators who view heavier athletes respond differently than those who view less heavy athletes?). METHOD: We used an experimental design to examine hypotheses derived from competing theories to determine whether exposure to female athletes of varying weight would adversely or beneficially impact female undergraduates (N = 152) who served as athletic event spectators. RESULTS: Analyses indicated that in this simulated study, female spectators' body image, eating disorder symptoms, self-esteem, and affective states were not impacted by the presence or by the magnitude of female athletes' weights in athletic event programs. CONCLUSION: The results imply that including athletes' weights in game-day programs at women's athletic events does not affect female spectators on an individual level. PMID- 25141095 TI - Evaluation of pain during hysterosalpingography with the use of balloon catheter vs metal cannula. AB - Our aim was to investigate the use of a balloon catheter device in comparison with metal cannula for hysterosalpingography (HSG) in terms of patient comfort. A total of 168 patients were randomised for HSG either with a balloon catheter (n = 83) or metal cannula (n = 85). Scores of pelvic pain during insertion of the devices, injection of the contrast medium and 1 h after the procedure were evaluated using the Wong Baker Faces Pain Rating Scale; complications and reinsertion rates were also noted. The pain scores were significantly lower in the balloon catheter group (p < 0.001). The reinsertion rate of metal cannula was higher (8.2% vs 2.4%) as well as the incidence of nausea being the most common short-term adverse effect (14.1% vs 1.2%) in the metal cannula group (p = 0.002). Performing HSG with a balloon catheter is advantageous for decreasing the pain and side-effects related to the procedure, when compared with the use of a metal cannula. PMID- 25141096 TI - Modulation of DNA-polyamide interaction by beta-alanine substitutions: a study of positional effects on binding affinity, kinetics and thermodynamics. AB - Hairpin polyamides (PAs) are an important class of sequence-specific DNA minor groove binders, and frequently employ a flexible motif, beta-alanine (beta), to reduce the molecular rigidity to maintain the DNA recognition register. To better understand the diverse effects that beta can have on DNA-PA binding affinity, selectivity, and especially kinetics, which have rarely been reported, we have initiated a detailed study for an eight-heterocyclic hairpin PA and its beta derivatives with their cognate and mutant sequences. With these derivatives, all internal pyrroles of the parent PA are systematically substituted with single or double betas. A set of complementary experiments have been conducted to evaluate the molecular interactions in detail: UV-melting, biosensor-surface plasmon resonance, circular dichroism and isothermal titration calorimetry. The beta substitutions generally weaken the binding affinities of these PAs with cognate DNA, and have large and diverse influences on PA binding kinetics in a position- and number-dependent manner. The DNA base mutations have also shown positional effects on the binding of a single PA. Besides the beta substitutions, the monocationic Dp group [3-(dimethylamino)propylamine] in parent PA has been modified into a dicationic Ta group (3,3'-diamino-N-methyldipropylamine) to minimize the frequently observed PA aggregation with ITC experiments. The results clearly show that the Ta modification not only maintains the DNA binding mode and affinity of PA, but also significantly reduces PA aggregation and allows the complete thermodynamic signature of eight-ring hairpin PA to be determined for the first time. This combined set of results significantly extends our understanding of the energetic basis of specific DNA recognition by PAs. PMID- 25141097 TI - Thiol-activated gem-dithiols: a new class of controllable hydrogen sulfide donors. AB - A class of novel thiol-activated H2S donors has been developed on the basis of the gem-dithiol template. These donors release H2S in the presence of cysteine or GSH in aqueous solutions as well as in cellular environments. PMID- 25141098 TI - Are there gender, racial or relationship differences in caregiver task difficulty, depressive symptoms and life changes among stroke family caregivers? AB - OBJECTIVE: To examine differences in caregiver perceptions of task difficulty, depressive symptoms and life changes based on caregiver characteristics of gender, race and type of relationship to the person with stroke. METHODS: A sample of 243 stroke caregivers (females n = 191; males n = 52; non-African Americans n = 184; African Americans n = 59; non-spouses n = 127; spouses n = 116) were interviewed by telephone within 8 weeks of the survivor's discharge to home. Measures included the Oberst Caregiving Burden Scale (OCBS) for task difficulty, Patient Health Questionnaire (PHQ-9) for depressive symptoms and Bakas Caregiving Outcomes Scale (BCOS) for life changes. Three general linear models computed differences in OCBS, PHQ9 and OCBS scores. RESULTS: Significant differences were found on the OCBS for females (p < 0.001) and African American spouses (p < 0.048); on the PHQ9 for females (p < 0.001), non-African Americans (p = 0.047), spouses (p = 0.003) and African-American spouses (p = 0.010); and on the BCOS for females (p = 0.008) and non-African Americans (p = 0.033). CONCLUSIONS: Findings suggest that female and non-African American stroke caregivers are relatively more likely to experience task difficulty, depressive symptoms and negative life changes as a result of providing care. African American spouses were also at risk. Tailoring interventions based on caregivers' characteristics may improve outcomes. PMID- 25141099 TI - Zinc modulates aluminium-induced oxidative stress and cellular injury in rat brain. AB - Dysregulation of metal homeostasis has been perceived as one of the key factors in the progression of neurodegeneration. Aluminium (Al) has been considered as a major risk factor, which is linked to several neurodegenerative diseases, especially Alzheimer's disease, whereas zinc (Zn) has been reported as a vital dietary element, which regulates a number of physiological processes in central nervous system. The present study was conducted to explore the protective potential of zinc, if any, in ameliorating neurotoxicity induced by aluminium. Male Sprague Dawley rats received either aluminium chloride (AlCl3) orally (100 mg kg(-1) b.wt. per day), zinc sulphate (ZnSO4) at a dose level of 227 mg L(-1) in drinking water or combined treatment of aluminium and zinc for 8 weeks. Aluminium treatment significantly elevated the levels of lipid peroxidation and reactive oxygen species as well as the activities of catalase, superoxide dismutase and glutathione reductase, which however were decreased following Zn co treatment of Al-treated rats. In contrast, Al treatment decreased the activities of glutathione-S-transferase as well as the levels of reduced glutathione, oxidised glutathione and total glutathione, but co-administration of Zn to Al treated animals increased these levels. Furthermore, Al treatment caused a significant increase in the levels of Fe and Mn as well as of Al but decreased the Zn and metallothionein levels. In the Zn-supplemented animals, the levels of Al, Fe, Mn were found to be significantly decreased, whereas the levels of metallothionein as well as Zn were increased. Moreover, histopathological alterations such as vacuolization and loss of Purkinje cells were also evident following Al treatment, which showed improvement upon Zn supplementation. Therefore, zinc has the potential to alleviate aluminium-induced neurodegeneration. PMID- 25141100 TI - Serum amyloid A-related inflammation is lowered by increased fruit and vegetable intake, while high-sensitive C-reactive protein, IL-6 and E-selectin remain unresponsive. AB - The present study assessed whether increased fruit and vegetable (F&V) intake reduced the concentrations of the inflammatory marker serum amyloid A (SAA) in serum, HDL2 and HDL3 and whether the latter reduction influenced any of the functional properties of these HDL subfractions. The present study utilised samples from two previous studies: (1) the FAVRIT (Fruit and Vegetable Randomised Intervention Trial) study - hypertensive subjects (systolic blood pressure (BP) range 140-190 mmHg; diastolic BP range 90-110 mmHg) were randomised to receive a 1-, 3- or 6-portion F&V/d intervention for 8 weeks, and (2) the ADIT (Ageing and Dietary Intervention Trial) study - older subjects (65-85 years) were randomised to receive a 2- or 5-portion F&V/d intervention for 16 weeks. HDL2 and HDL3 were isolated by rapid ultracentrifugation. Measurements included the following: serum high-sensitive C-reactive protein (hsCRP) by an immunoturbidimetric assay; serum IL-6 and E-selectin and serum-, HDL2- and HDL3-SAA by ELISA procedures; serum-, HDL2- and HDL3-cholesterol ester transfer protein (CETP) activity by a fluorometric assay. Although the concentrations of hsCRP, IL-6 and E-selectin were unaffected by increasing F&V intake in both studies (P>0.05 for all comparisons), those of SAA in HDL3 decreased in the FAVRIT cohort (P= 0.049) and those in HDL2 and HDL3 decreased in the ADIT cohort (P= 0.035 and 0.032), which was accompanied by a decrease in the activity of CETP in HDL3 in the FAVRIT cohort (P= 0.010) and in HDL2 in the ADIT cohort (P= 0.030). These results indicate that SAA responds to increased F&V intake, while other inflammatory markers remain unresponsive, and this leads to changes in HDL2 and HDL3, which may influence their antiatherogenic potential. Overall, the present study provides tangible evidence of the effectiveness of increased F&V intake, which may be of use to health policy makers and the general public. PMID- 25141101 TI - Prenatal diagnosis of the acute meconium peritonitis secondary to ileum volvulus perforation: a case report. AB - This is an unusual case in comparison to other sonographically described prenatal cases due to very early diagnosis and surgical intervention following prompt delivery. A 40-year-old pregnant, ultrasonography showed presence of cystic structure in the fetal abdomen that was consistent with intestinal dilatation. At 32 weeks' of gestation, repeat ultrasound showed collapse of the bowel dilatation along with the presence of hyperechogenic fluid in the fetal abdominal cavity. Cesarean section was performed. The clinical utility of this report is the recognition that meconium peritonitis (MP) may be diagnosed in the acute phase with typical ultrasound features, and should be considered in the differential diagnoses of cases presented with reduced fetal movements. Although it appears that morbidity and mortality in MP cases depend upon gestational age, this case report may help to manage similar cases for defining the appropriate delivery time and treatment modality after prenatal identification of the problem. PMID- 25141102 TI - Recent advances of stem cell therapy for retinitis pigmentosa. AB - Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive loss of photoreceptors and eventually leads to retina degeneration and atrophy. Until now, the exact pathogenesis and etiology of this disease has not been clear, and many approaches for RP therapies have been carried out in animals and in clinical trials. In recent years, stem cell transplantation-based attempts made some progress, especially the transplantation of bone marrow derived mesenchymal stem cells (BMSCs). This review will provide an overview of stem cell-based treatment of RP and its main problems, to provide evidence for the safety and feasibility for further clinical treatment. PMID- 25141103 TI - MicroRNAs, genomic instability and cancer. AB - MicroRNAs (miRNAs) are small non-coding RNA transcripts approximately 20 nucleotides in length that regulate expression of protein-coding genes via complementary binding mechanisms. The last decade has seen an exponential increase of publications on miRNAs, ranging from every aspect of basic cancer biology to diagnostic and therapeutic explorations. In this review, we summarize findings of miRNA involvement in genomic instability, an interesting but largely neglected topic to date. We discuss the potential mechanisms by which miRNAs induce genomic instability, considered to be one of the most important driving forces of cancer initiation and progression, though its precise mechanisms remain elusive. We classify genomic instability mechanisms into defects in cell cycle regulation, DNA damage response, and mitotic separation, and review the findings demonstrating the participation of specific miRNAs in such mechanisms. PMID- 25141104 TI - High-resolution imaging reveals new features of nuclear export of mRNA through the nuclear pore complexes. AB - The nuclear envelope (NE) of eukaryotic cells provides a physical barrier for messenger RNA (mRNA) and the associated proteins (mRNPs) traveling from sites of transcription in the nucleus to locations of translation processing in the cytoplasm. Nuclear pore complexes (NPCs) embedded in the NE serve as a dominant gateway for nuclear export of mRNA. However, the fundamental characterization of export dynamics of mRNPs through the NPC has been hindered by several technical limits. First, the size of NPC that is barely below the diffraction limit of conventional light microscopy requires a super-resolution microscopy imaging approach. Next, the fast transit of mRNPs through the NPC further demands a high temporal resolution by the imaging approach. Finally, the inherent three dimensional (3D) movements of mRNPs through the NPC demand the method to provide a 3D mapping of both transport kinetics and transport pathways of mRNPs. This review will highlight the recently developed super-resolution imaging techniques advanced from 1D to 3D for nuclear export of mRNPs and summarize the new features in the dynamic nuclear export process of mRNPs revealed from these technical advances. PMID- 25141105 TI - Immunoproteome of Aspergillus fumigatus using sera of patients with invasive aspergillosis. AB - Invasive aspergillosis is a life-threatening lung or systemic infection caused by the opportunistic mold Aspergillus fumigatus. The disease affects mainly immunocompromised hosts, and patients with hematological malignances or who have been submitted to stem cell transplantation are at high risk. Despite the current use of PlateliaTM Aspergillus as a diagnostic test, the early diagnosis of invasive aspergillosis remains a major challenge in improving the prognosis of the disease. In this study, we used an immunoproteomic approach to identify proteins that could be putative candidates for the early diagnosis of invasive aspergillosis. Antigenic proteins expressed in the first steps of A. fumigatus germination occurring in a human host were revealed using 2-D Western immunoblots with the serum of patients who had previously been classified as probable and proven for invasive aspergillosis. Forty antigenic proteins were identified using mass spectrometry (MS/MS). A BLAST analysis revealed that two of these proteins showed low homology with proteins of either the human host or etiological agents of other invasive fungal infections. To our knowledge, this is the first report describing specific antigenic proteins of A. fumigatus germlings that are recognized by sera of patients with confirmed invasive aspergillosis who were from two separate hospital units. PMID- 25141106 TI - New milk protein-derived peptides with potential antimicrobial activity: an approach based on bioinformatic studies. AB - New peptides with potential antimicrobial activity, encrypted in milk protein sequences, were searched for with the use of bioinformatic tools. The major milk proteins were hydrolyzed in silico by 28 enzymes. The obtained peptides were characterized by the following parameters: molecular weight, isoelectric point, composition and number of amino acid residues, net charge at pH 7.0, aliphatic index, instability index, Boman index, and GRAVY index, and compared with those calculated for known 416 antimicrobial peptides including 59 antimicrobial peptides (AMPs) from milk proteins listed in the BIOPEP database. A simple analysis of physico-chemical properties and the values of biological activity indicators were insufficient to select potentially antimicrobial peptides released in silico from milk proteins by proteolytic enzymes. The final selection was made based on the results of multidimensional statistical analysis such as support vector machines (SVM), random forest (RF), artificial neural networks (ANN) and discriminant analysis (DA) available in the Collection of Anti Microbial Peptides (CAMP database). Eleven new peptides with potential antimicrobial activity were selected from all peptides released during in silico proteolysis of milk proteins. PMID- 25141107 TI - Cross-sectional study comparing different therapeutic modalities for cystic lymphangiomas in children. AB - OBJECTIVE: Here, we describe our experience with different therapeutic modalities used to treat cystic lymphangiomas in children in our hospital, including single therapy with OK-432, bleomycin and surgery, and a combination of the three modalities. METHODS: We performed a retrospective, cross-sectional study including patients treated from 1998 to 2011. The effects on macrocystic lymphangiomas and adverse reactions were evaluated. Twenty-nine children with cystic lymphangiomas without any previous treatment were included. Under general anesthesia, patients given sclerosing agents underwent puncture of the lesion (guided by ultrasound when necessary) and complete aspiration of the intralesional liquid. The patients were evaluated with ultrasound and clinical examinations for a maximum follow-up time of 4 years. RESULTS: The proportions of patients considered cured after the first therapeutic approach were 44% in the surgery group, 29% in the bleomycin group and 31% in the OK-432 group. These proportions were not significantly different. Sequential treatment increased the rates of curative results to 71%, 74% and 44%, respectively, after the final treatment, which in our case was approximately 1.5 applications per patient. CONCLUSION: The results of this study indicate that most patients with cystic lymphangiomas do not show complete resolution after the initial therapy, regardless of whether the therapy is surgical or involves the use of sclerosing agents. To achieve complete resolution of the lesions, either multiple operations or a combination of surgery and sclerotherapy must be used and should be tailored to the characteristics of each patient. PMID- 25141108 TI - Treatment priorities in oncology: do we want to live longer or better? AB - OBJECTIVES: Despite the progress achieved in the fight against cancer over the past several years, assessing the needs, goals and preferences of patients with cancer is of the utmost importance for the delivery of health care. We sought to assess priorities regarding quantity versus quality of life among Brazilian patients, comparing them with individuals without cancer. METHODS: Using a questionnaire presenting four hypothetical cancer cases, we interviewed cancer patients, oncology health-care professionals and laypersons, most of whom had administrative functions in our hospital. RESULTS: A total of 214 individuals participated: 101 patients, 44 health-care professionals and 69 laypersons. The mean ages in the three groups were 56, 34 and 31 years old, respectively (p<0.001). The patients had gastrointestinal (25%), breast (22%), hematologic (10%), lung (8%) or other tumors (36%) and the tumor-node- metastasis (TNM) stage was I, II, III or IV in 22%, 13%, 34% and 31% of cases, respectively. Treatment priorities differed significantly among the three groups (p = 0.005), with survival time being a higher priority for patients than for the other two groups and with opposite trends regarding quality of life. In multivariate analysis, the age and sex distributions were not associated with the choice to maximize quality of life. In this limited sample of cancer patients, there were no associations between treatment priorities and disease stages. CONCLUSIONS: Both survival time and quality of life appeared to be important to cancer patients, oncology health care professionals and laypersons, but survival time seemed to have higher priority for people diagnosed with cancer than for healthy people. Additionally, survival seemed to be more important than quality of life for all three groups assessed. PMID- 25141110 TI - Effects of placebo-controlled continuous and pulsed ultrasound treatments on carpal tunnel syndrome: a randomized trial. AB - OBJECTIVE: The aim of this placebo-controlled study was to evaluate the effects of pulsed and continuous ultrasound treatments combined with splint therapy on patients with mild and moderate idiopathic carpal tunnel syndrome. METHODS: The study included 46 carpal tunnel syndrome patients who were randomly divided into 3 groups. The first group (n = 15) received a 0 W/cm2 ultrasound treatment (placebo); the second group (n = 16) received a 1.0 W/cm2 continuous ultrasound treatment and the third group (n = 15) received a 1.0 W/cm2 1:4 pulsed ultrasound treatment 5 days a week for a total of 15 sessions. All patients also wore night splints during treatment period. Pre-treatment and post-treatment Visual Analogue Scale, Symptom Severity Scale and Functional Status Scale scores, median nerve motor conduction velocity and distal latency and sensory conduction velocities of the median nerve in the 2nd finger and palm were compared. Clinicaltrials.gov: NCT02054247. RESULTS: There were significant improvements in all groups in terms of the post-treatment Functional Status Scale score (p<0.05 for all groups), Symptom Severity Scale score (first group: p<0.05, second group: p<0.01, third group: p<0.001) and Visual Analogue Scale score (first and third groups: p<0.01, second group: p<0.001). Sensory conduction velocities improved in the second and third groups (p<0.01). Distal latency in the 2nd finger showed improvement only in the third group (p<0.01) and action potential latency in the palm improved only in the second group (p<0.05). CONCLUSION: The results of this study suggest that splinting therapy combined with placebo and pulsed or continuous ultrasound have similar effects on clinical improvement. Patients treated with continuous and pulsed ultrasound showed electrophysiological improvement; however, the results were not superior to those of the placebo. PMID- 25141109 TI - Breast hamartoma: a clinicopathologic analysis of 27 cases and a literature review. AB - OBJECTIVES: Breast hamartoma is an uncommon breast tumor that accounts for approximately 4.8% of all benign breast masses. The pathogenesis is still poorly understood and breast hamartoma is not a well-known disorder, so its diagnosis is underestimated by clinicians and pathologists. This study was designed to present our experience with breast hamartoma, along with a literature review. METHOD: We reviewed the demographic data, pathologic analyses and imaging and results of patients diagnosed with breast hamartoma between December 2003 and September 2013. RESULTS: In total, 27 cases of breast hamartoma operated in the Ankara University Medicine Faculty's Department of General Surgery were included in the study. All patients were female and the mean age was 41.8+/-10.8 years. The mean tumor size was 3.9+/-2.7 cm. Breast ultrasound was performed on all patients before surgery. The most common additional lesion was epithelial hyperplasia (22.2%). Furthermore, lobular carcinoma in situ was identified in one case and invasive ductal carcinoma was observed in another case. Immunohistochemical staining revealed myoid hamartoma in one case (3.7%). CONCLUSION: Breast hamartomas are rare benign lesions that may be underdiagnosed because of the categorization of hamartomas as fibroadenomas by pathologists. Pathologic examinations can show variability from one case to another. Thus, the true incidence may be higher than the literature indicates. PMID- 25141111 TI - Controlled medial branch anesthetic block in the diagnosis of chronic lumbar facet joint pain: the value of a three-month follow-up. AB - OBJECTIVES: To verify the incidence of facetary and low back pain after a controlled medial branch anesthetic block in a three-month follow-up and to verify the correlation between the positive results and the demographic variables. METHODS: Patients with chronic lumbar pain underwent a sham blockade (with a saline injection) and then a controlled medial branch block. Their symptoms were evaluated before and after the sham injection and after the real controlled medial branch block; the symptoms were reevaluated after one day and one week, as well as after one, two and three months using the visual analog scale. We searched for an association between the positive results and the demographic characteristics of the patients. RESULTS: A total of 104 controlled medial branch blocks were performed and 54 patients (52%) demonstrated >50% improvements in pain after the blockade. After three months, lumbar pain returned in only 18 individuals, with visual analogue scale scores >4. Therefore, these patients were diagnosed with chronic facet low back pain. The three-months of follow-up after the controlled medial branch block excluded 36 patients (67%) with false positive results. The results of the controlled medial branch block were not correlated to sex, age, pain duration or work disability but were correlated with patient age (p<0.05). CONCLUSION: Patient diagnosis with a controlled medial branch block proved to be effective but was not associated with any demographic variables. A three-month follow-up is required to avoid a high number of false positives. PMID- 25141112 TI - Fluid distribution kinetics during cardiopulmonary bypass. AB - OBJECTIVE: The purpose of this study was to examine the isovolumetric distribution kinetics of crystalloid fluid during cardiopulmonary bypass. METHODS: Ten patients undergoing coronary artery bypass grafting participated in this prospective observational study. The blood hemoglobin and the serum albumin and sodium concentrations were measured repeatedly during the distribution of priming solution (Ringer's acetate 1470 ml and mannitol 15% 200 ml) and initial cardioplegia. The rate of crystalloid fluid distribution was calculated based on 3-min Hb changes. The preoperative blood volume was extrapolated from the marked hemodilution occurring during the onset of cardiopulmonary bypass. Clinicaltrials.gov: NCT01115166. RESULTS: The distribution half-time of Ringer's acetate averaged 8 minutes, corresponding to a transcapillary escape rate of 0.38 ml/kg/min. The intravascular albumin mass increased by 5.4% according to mass balance calculations. The preoperative blood volume, as extrapolated from the drop in hemoglobin concentration by 32% (mean) at the beginning of cardiopulmonary bypass, was 0.6-1.2 L less than that estimated by anthropometric methods (p<0.02). The mass balance of sodium indicated a translocation from the intracellular to the extracellular fluid space in 8 of the 10 patients, with a median volume of 236 ml. CONCLUSIONS: The distribution half-time of Ringer's solution during isovolumetric cardiopulmonary bypass was 8 minutes, which is the same as for crystalloid fluid infusions in healthy subjects. The intravascular albumin mass increased. Most patients were hypovolemic prior to the start of anesthesia. Intracellular edema did not occur. PMID- 25141113 TI - The association of vitamin D deficiency with non-alcoholic fatty liver disease. AB - OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), gamma-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3+/-8.9 ng/dl, p<0.001) compared with those of the control group (20+/-13.6 ng/dl). CONCLUSIONS: In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed. PMID- 25141114 TI - Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis. AB - OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9+/-1.2 and 10.96+/-1.2 g/dL (p = 0.89) in the Bio Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy and safety. PMID- 25141115 TI - Effects of ovariectomy on the secretory apparatus in the right atrial cardiomyocytes of middle-aged mice. AB - OBJECTIVE: The aim of the present study was to evaluate the effects of ovariectomy on the secretory apparatus of natriuretic peptides in right atrial cardiomyocytes. METHODS: Nine-month-old mice underwent bilateral ovariectomy or sham surgery. The blood exam of the ovariectomized mice showed results consistent with castrated females. Systolic blood pressure was measured after ovariectomy (9 mo of age) and at the moment of sacrifice (12 mo of age). Fragments of the right atrium were collected and prepared for electron microscopy examination. The following variables were quantified: the quantitative density and area of the natriuretic peptide granules, the relative volume of euchromatin in the nucleus, the number of pores per 10 MUm of the nuclear membrane and the relative volumes of the mitochondria and Golgi complex. RESULTS: The cardiomyocytes obtained from ovariectomized mice indicated that the quantitative density and the area of secretory granules of natriuretic peptides were significantly lower compared with the sham-operated mice. Furthermore, there was a decrease in the relative volume of euchromatin, a lower density of nuclear pores, and lower relative volumes of the mitochondria and Golgi complex in the ovariectomized mice compared with the sham-operated mice. These findings suggest a pool with a low turnover rate, i.e., low synthesis and elimination of natriuretic peptides. CONCLUSION: A lack of estrogen caused hypotrophy of the secretory apparatus in right atrial cardiomyocytes that could explain the weak synthesis of natriuretic peptides in mice. Furthermore, one of the mechanisms of blood pressure control was lost, which may explain, in part, the elevated blood pressure in ovariectomized mice. PMID- 25141116 TI - Neuroprotective effect of epidural hypothermia after spinal cord lesion in rats. AB - OBJECTIVES: To evaluate the neuroprotective effect of epidural hypothermia in rats subjected to experimental spinal cord lesion. METHODS: Wistar rats (n = 30) weighing 320-360 g were randomized to two groups (hypothermia and control) of 15 rats per group. A spinal cord lesion was induced by the standardized drop of a 10 g weight from a height of 2.5 cm, using the New York University Impactor, after laminectomy at the T9-10 level. Rats in the hypothermia group underwent epidural hypothermia for 20 minutes immediately after spinal cord injury. Motor function was assessed for six weeks using the Basso, Beattie and Bresnahan motor scores and the inclined plane test. At the end of the final week, the rats' neurological status was monitored by the motor evoked potential test and the results for the two groups were compared. RESULTS: Analysis of the Basso, Beattie and Bresnahan scores obtained during the six-week period indicated that there were no significant differences between the two groups. There was no significant difference between the groups in the inclined plane test scores during the six week period. Furthermore, at the end of the study, the latency and amplitude values of the motor evoked potential test were not significantly different between the two groups. CONCLUSION: Hypothermia did not produce a neuroprotective effect when applied at the injury level and in the epidural space immediately after induction of a spinal cord contusion in Wistar rats. PMID- 25141117 TI - Update on hypertrophic scar treatment. AB - Scar formation is a consequence of the wound healing process that occurs when body tissues are damaged by a physical injury. Hypertrophic scars and keloids are pathological scars resulting from abnormal responses to trauma and can be itchy and painful, causing serious functional and cosmetic disability. The current review will focus on the definition of hypertrophic scars, distinguishing them from keloids and on the various methods for treating hypertrophic scarring that have been described in the literature, including treatments with clearly proven efficiency and therapies with doubtful benefits. Numerous methods have been described for the treatment of abnormal scars, but to date, the optimal treatment method has not been established. This review will explore the differences between different types of nonsurgical management of hypertrophic scars, focusing on the indications, uses, mechanisms of action, associations and efficacies of the following therapies: silicone, pressure garments, onion extract, intralesional corticoid injections and bleomycin. PMID- 25141118 TI - Adolescents with HIV and facial lipoatrophy: response to facial stimulation. AB - OBJECTIVES: This study evaluated the effects of facial stimulation over the superficial muscles of the face in individuals with facial lipoatrophy associated with human immunodeficiency virus (HIV) and with no indication for treatment with polymethyl methacrylate. METHOD: The study sample comprised four adolescents of both genders ranging from 13 to 17 years in age. To participate in the study, the participants had to score six or less points on the Facial Lipoatrophy Index. The facial stimulation program used in our study consisted of 12 weekly 30-minute sessions during which individuals received therapy. The therapy consisted of intra- and extra-oral muscle contraction and stretching maneuvers of the zygomaticus major and minor and the masseter muscles. Pre- and post-treatment results were obtained using anthropometric static measurements of the face and the Facial Lipoatrophy Index. RESULTS: The results suggest that the therapeutic program effectively improved the volume of the buccinators. No significant differences were observed for the measurements of the medial portion of the face, the lateral portion of the face, the volume of the masseter muscle, or Facial Lipoatrophy Index scores. CONCLUSION: The results of our study suggest that facial maneuvers applied to the superficial muscles of the face of adolescents with facial lipoatrophy associated with HIV improved the facial area volume related to the buccinators muscles. We believe that our results will encourage future research with HIV patients, especially for patients who do not have the possibility of receiving an alternative aesthetic treatment. PMID- 25141119 TI - Investigation on the evolution of N-containing organic compounds during pyrolysis of sewage sludge. AB - Pyrolysis is an emerging technology for the disposal of huge amounts of sewage sludge. However, the thermochemical decomposition mechanism of organic compounds in sludge is still unclear. We adopt a novel online TG-FTIR-MS technology to investigate the pyrolysis of sludge. The sludge samples were pyrolyzed from 150 to 800 degrees C with heating rates of 10, 50, and 200 K min(-1). We found for the first time that the heating rate of pyrolysis can significantly change the species of liquid organic compounds produced, but cannot change the gaseous species produced under the same conditions. The contents of produced gas and liquid compounds, most of which were produced at 293-383 degrees C, are influenced by both the heating rate and temperature of pyrolysis. The results also showed that heterocyclic-N, amine-N, and nitrile-N compounds are obtained from the decomposition of N-compounds in sludge, such as pyrrolic-N, protein-N, amine-N, and pyridinic-N. Heterocyclic-N compounds are the dominant N-containing products, which can be due to the thermochemical decomposition of pyridine-N and pyrrole-N, whereas fewer amine-N compounds are produced during the pyrolysis. A mechanism for the decomposition of N-containing compounds in sludge is proposed based on the obtained data. PMID- 25141120 TI - A new approach to standardize multicenter studies: mobile lab technology for the German Environmental Specimen Bank. AB - Technical progress has simplified tasks in lab diagnosis and improved quality of test results. Errors occurring during the pre-analytical phase have more negative impact on the quality of test results than errors encountered during the total analytical process. Different infrastructures of sampling sites can highly influence the quality of samples and therewith of analytical results. Annually the German Environmental Specimen Bank (ESB) collects, characterizes, and stores blood, plasma, and urine samples of 120-150 volunteers each on four different sampling sites in Germany. Overarching goal is to investigate the exposure to environmental pollutants of non-occupational exposed young adults combining human biomonitoring with questionnaire data. We investigated the requirements of the study and the possibility to realize a highly standardized sampling procedure on a mobile platform in order to increase the required quality of the pre-analytical phase. The results lead to the development of a mobile epidemiologic laboratory (epiLab) in the project "Labor der Zukunft" (future's lab technology). This laboratory includes a 14.7 m(2) reception area to record medical history and exposure-relevant behavior, a 21.1 m(2) examination room to record dental fillings and for blood withdrawal, a 15.5 m(2) biological safety level 2 laboratory to process and analyze samples on site including a 2.8 m(2) personnel lock and a 3.6 m2 cryofacility to immediately freeze samples. Frozen samples can be transferred to their final destination within the vehicle without breaking the cold chain. To our knowledge, we herewith describe for the first time the implementation of a biological safety laboratory (BSL) 2 lab and an epidemiologic unit on a single mobile platform. Since 2013 we have been collecting up to 15.000 individual human samples annually under highly standardized conditions using the mobile laboratory. Characterized and free of alterations they are kept ready for retrospective analyses in their final archive, the German ESB. PMID- 25141121 TI - Impact of aspirin and clopidogrel interruption on platelet function in patients undergoing major vascular surgery. AB - AIMS: To investigate functional platelet recovery after preoperative withdrawal of aspirin and clopidogrel and platelet function 5 days after treatment resumption. METHODS/RESULTS: We conducted an observational study, which prospectively included consecutive patients taking aspirin, taking clopidogrel, and untreated controls (15 patients in each group). The antiplatelet drugs were withdrawn five days before surgery (baseline) and were reintroduced two days after surgery. Platelet function was evaluated by optical aggregation in the presence of collagen, arachidonic acid (aspirin) and ADP (clopidogrel) and by VASP assay (clopidogrel). Platelet-leukocyte complex (PLC) level was quantified at each time-point. At baseline, platelet function was efficiently inhibited by aspirin and had recovered fully in most patients 5 days after drug withdrawal. PLC levels five days after aspirin reintroduction were similar to baseline (+4+/ 10%; p = 0.16), in line with an effective platelet inhibition. Chronic clopidogrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after clopidogrel reintroduction (+10+/-15%; p = 0.02), compared to baseline. CONCLUSIONS: Aspirin withdrawal 5 days before high-bleeding risk procedures was associated with functional platelet recovery, and its reintroduction two days after surgery restored antiplaletet efficacy five days later. This was not the case of clopidogrel, and further work is therefore needed to define its optimal perioperative management. PMID- 25141122 TI - Simulating the impact of improved cardiovascular risk interventions on clinical and economic outcomes in Russia. AB - OBJECTIVES: Russia faces a high burden of cardiovascular disease. Prevalence of all cardiovascular risk factors, especially hypertension, is high. Elevated blood pressure is generally poorly controlled and medication usage is suboptimal. With a disease-model simulation, we forecast how various treatment programs aimed at increasing blood pressure control would affect cardiovascular outcomes. In addition, we investigated what additional benefit adding lipid control and smoking cessation to blood pressure control would generate in terms of reduced cardiovascular events. Finally, we estimated the direct health care costs saved by treating fewer cardiovascular events. METHODS: The Archimedes Model, a detailed computer model of human physiology, disease progression, and health care delivery was adapted to the Russian setting. Intervention scenarios of achieving systolic blood pressure control rates (defined as systolic blood pressure <140 mmHg) of 40% and 60% were simulated by modifying adherence rates of an antihypertensive medication combination and compared with current care (23.9% blood pressure control rate). Outcomes of major adverse cardiovascular events; cerebrovascular event (stroke), myocardial infarction, and cardiovascular death over a 10-year time horizon were reported. Direct health care costs of strokes and myocardial infarctions were derived from official Russian statistics and tariff lists. RESULTS: To achieve systolic blood pressure control rates of 40% and 60%, adherence rates to the antihypertensive treatment program were 29.4% and 65.9%. Cardiovascular death relative risk reductions were 13.2%, and 29.6%, respectively. For the current estimated 43,855,000-person Russian hypertensive population, each control-rate scenario resulted in an absolute reduction of 1.0 million and 2.4 million cardiovascular deaths, and a reduction of 1.2 million and 2.7 million stroke/myocardial infarction diagnoses, respectively. Averted direct costs from current care levels ($7.6 billion [in United States dollars]) were $1.1 billion and $2.6 billion, respectively. PMID- 25141124 TI - Impact of hypokalemia on electromechanical window, excitation wavelength and repolarization gradients in guinea-pig and rabbit hearts. AB - Normal hearts exhibit a positive time difference between the end of ventricular contraction and the end of QT interval, which is referred to as the electromechanical (EM) window. Drug-induced prolongation of repolarization may lead to the negative EM window, which was proposed to be a novel proarrhythmic marker. This study examined whether abnormal changes in the EM window may account for arrhythmogenic effects produced by hypokalemia. Left ventricular pressure, electrocardiogram, and epicardial monophasic action potentials were recorded in perfused hearts from guinea-pig and rabbit. Hypokalemia (2.5 mM K(+)) was found to prolong repolarization, reduce the EM window, and promote tachyarrhythmia. Nevertheless, during both regular pacing and extrasystolic excitation, the increased QT interval invariably remained shorter than the duration of mechanical systole, thus yielding positive EM window values. Hypokalemia-induced arrhythmogenicity was associated with slowed ventricular conduction, and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Hypokalemia also evoked non-uniform prolongation of action potential duration in distinct epicardial regions, which resulted in increased spatial variability in the repolarization time. These findings suggest that arrhythmogenic effects of hypokalemia are not accounted for by the negative EM window, and are rather attributed to abnormal changes in ventricular conduction times, refractoriness, excitation wavelength, and spatial repolarization gradients. PMID- 25141125 TI - Study of the interaction of water with the aqua-soluble dimeric complex [RuCp(PTA)2-MU-CN-1kappaC:2kappa(2)N-RuCp(PTA)2](CF3SO3) (PTA = 1,3,5-triaza-7 phosphaadamantane) by neutron and X-ray diffraction in solution. AB - The study of an aqueous solution of [RuCp(PTA)2-MU-CN-1kappaC:2kappa(2)N RuCp(PTA)2](CF3SO3) by neutron and X-ray diffraction revealed surprising details as to how the water molecules interact with the complex and affect its properties. The present communication demonstrates the applicability of sophisticated scattering techniques in combination with theoretical calculations to the study of coordination compounds in aqueous solution. PMID- 25141123 TI - Comparative persistence of the TNF antagonists in rheumatoid arthritis--a population-based cohort study. AB - OBJECTIVE: To compare persistence with tumor necrosis factor alpha (TNF) antagonists among rheumatoid arthritis patients in British Columbia. Treatment persistence has been suggested as a proxy for real-world therapeutic benefit and harm of treatments for chronic non-curable diseases, including rheumatoid arthritis. We hypothesized that the different pharmacological characteristics of infliximab, adalimumab and etanercept cause statistically and clinically significant differences in persistence. METHODS: We conducted a population-based cohort study using administrative health data from the Canadian province of British Columbia. The study cohort included rheumatoid arthritis patients who initiated the first course of a TNF antagonist between 2001 and 2008. Persistence was measured as the time between first dispensing to discontinuation. Drug discontinuation was defined as a drug-free interval of 180 days or switching to another TNF antagonist, anakinra, rituximab or abatacept. Persistence was estimated and compared using survival analysis. RESULTS: The study cohort included 2,923 patients, 63% treated with etanercept. Median persistence in years (95% confidence interval) with infliximab was 3.7 (2.9-4.9), with adalimumab 3.3 (2.6-4.1) and with etanercept 3.8 (3.3-4.3). Similar risk of discontinuation was observed for the three drugs: the hazard ratio (95% confidence interval) was 0.98 (0.85-1.13) comparing infliximab with etanercept, 0.95 (0.78-1.15) comparing infliximab with adalimumab and 1.04 (0.88-1.22) comparing adalimumab with etanercept. CONCLUSIONS: Similar persistence was observed with infliximab, adalimumab and etanercept in rheumatoid arthritis patients during the first 9 years of use. If treatment persistence is a good proxy for the therapeutic benefit and harm of these drugs, then this finding suggests that the three drugs share an overall similar benefit-harm profile in rheumatoid arthritis patients. PMID- 25141126 TI - Association of the G473A polymorphism and expression of lysyl oxidase with breast cancer risk and survival in European women: a hospital-based case-control study. AB - BACKGROUND: Lysyl oxidase (LOX) is an extracellular enzyme essential for the covalent crosslinking of extracellular matrix proteins and may also have additional functions. LOX expression can be both up- and downregulated in cancer and is associated both with tumour suppression and metastasis progression. The G473A polymorphism (rs1800449) results in the Arg158Gln amino acid substitution in the LOX propeptide, compromises its tumour suppressive activity, and was associated with an increased breast cancer risk in a Chinese Han population. In the first hospital-based case-control study in European women, we aimed at investigating the association of LOX expression and the G473A polymorphism with breast cancer risk and survival in unselected and estrogen receptor (ER) negative patients. METHODOLOGY/PRINCIPAL FINDINGS: The G473A polymorphism was genotyped in 386 breast cancer patients and 243 female controls. Moreover, LOX mRNA expression was quantified in the tumors of 105 patients by qRT-PCR. We found that the minor A-allele of this polymorphism is associated with a later age at breast cancer onset, a trend towards a decreased disease-free and metastasis-free survival, but not with an increased breast cancer risk. LOX mRNA expression was significantly elevated in tumours of patients older than 55 years, postmenopausal patients, estrogen receptor positive tumours, and p53 negative tumours, but was unaffected by G473A genotype in tumours and breast cancer cell lines. High LOX expression was associated with a poor disease-free and metastasis-free survival in ER negative but not ER positive patients. LOX expression was an independent prognostic parameter in multivariate analysis, whereas G473A genotype was not. A small, distinct subgroup of the ER negative patients was identified which exhibited a considerably elevated LOX expression and a very poor disease-free (p = 0.001) and metastasis-free survival (p = 0.0003). CONCLUSIONS/SIGNIFICANCE: This newly identified ER negative/LOX high subgroup may be a suitable collective for future individualized breast cancer diagnosis and therapy. PMID- 25141127 TI - Modeling the solvation of nonpolar amino acids in guanidinium chloride solutions. AB - It is common to denature proteins by using high temperatures or by adding guanidinium chloride (GdmCl). However, the physical mechanism of denaturation is not well understood. Based on extensive experimental data, we developed a thermodynamic binding-polynomial model for the process of transferring nonpolar amino acids from water into GdmCl solutions, as a function of temperature and GdmCl concentration. To mimic nonpolar amino acids, we utilized the model compound, N-acetyl-tryptophanamide (NATA). We find that all nonpolar amino acids behave like NATA, with a scale factor linearly dependent on the surface area. Our model with three thermodynamic parameters fully captures the nonlinear dependencies on both the temperature and GdmCl concentration: binding the first guanidinium ion (Gdm(+)) to NATA has favorable entropy and unfavorable enthalpy of desolvation (DeltaS = +11.7 cal/mol, DeltaH = +3.9 kcal/mol), while cooperativity of binding a second Gdm(+) has a small contribution (K = 0.032 +/- 0.003). This model may be useful for a better understanding of protein denaturation by temperature and GdmCl. PMID- 25141128 TI - Prostate cancer antigen-3 (PCA3) and PCA3-based nomograms in the diagnosis of prostate cancer: an external validation of Hansen's nomogram on a Norwegian cohort. AB - OBJECTIVE: The aim of this study was to test the ability of prostate cancer antigen-3 (PCA3) and Hansen's PCA3-based nomogram to predict prostate cancer (PCa) probability in a Norwegian cohort, with the goal of reducing unnecessary biopsies. MATERIAL AND METHODS: Altogether, 127 consecutive patients were recruited to this study at Haukeland University Hospital, Norway. Prostate specific antigen (PSA), PCA3 score, digital rectal examination (DRE), prostate volume (Pvol) and age were determined. All patients had an extended 10-core biopsy. The performance of PCA3 score and Hansen's nomogram was tested. RESULTS: There were 124 evaluable patients. Among these, 59 patients had PCa on the initial biopsies. Mean PSA, PCA3 score and age were significantly higher and Pvol was significantly lower in patients with PCa. PCA3 scores of 35 and 21 led to a sensitivity of 71% and 81% and specificity of 72% and 55%, respectively. Hansen's nomogram gave an area under the curve (AUC) of 0.806. The intraclass correlation was 0.959 (Cronbach's alpha). Applied to this material, PCa would be missed in 15.2% of patients when applying the suggested threshold probability of 30%, among whom 66.7% had high-grade PCa. With a threshold probability of 20% only one patient had PCa and this was low grade. CONCLUSIONS: Hansen's PCA3-based nomogram is valid for this cohort. A threshold probability of 20% seems more adequate than 30% for this less screened cohort. PCA3 score only affects the biopsy indication in some patients and is recommended only for this subset. The results need to be confirmed in a larger study. PMID- 25141132 TI - Colorimetric humidity sensor based on liquid composite materials for the monitoring of food and pharmaceuticals. AB - Using supported ionic-liquid membrane (SILM)-inspired methodologies, we have synthesized, characterized, and developed a humidity sensor by coating a liquid composite material onto a hygroscopic, porous substrate. Similar to pH paper, the sensor responds to the environment's relative humidity and changes color accordingly. The humidity indicator is prepared by casting a few microliters of low-toxicity reagents on a nontoxic substrate. The sensing material is a newly synthesized liquid composite that comprises a hygroscopic medium for environmental humidity capture and a color indicator that translates the humidity level into a distinct color change. Sodium borohydride was used to form a liquid composite medium, and DenimBlu30 dye was used as a redox indicator. The liquid composite medium provides a hygroscopic response to the relative humidity, and DenimBlu30 translates the chemical changes into a visual change from yellow to blue. The borate-redox dye-based humidity sensor was prepared, and then Fourier transform infrared spectroscopy, differential scanning calorimetry, and image analysis methods were used to characterize the chemical composition, optimize synthesis, and gain insight into the sensor reactivity. Test results indicated that this new sensing material can detect relative humidity in the range of 5 100% in an irreversible manner with good reproducibility and high accuracy. The sensor is a low-cost, highly sensitive, easy-to-use humidity indicator. More importantly, it can be easily packaged with products to monitor humidity levels in pharmaceutical and food packaging. PMID- 25141131 TI - Acceleration and deceleration capacity of fetal heart rate in an in-vivo sheep model. AB - BACKGROUND: Fetal heart rate (FHR) variability is an indirect index of fetal autonomic nervous system (ANS) integrity. FHR variability analysis in labor fails to detect early hypoxia and acidemia. Phase-rectified signal averaging (PRSA) is a new method of complex biological signals analysis that is more resistant to non stationarities, signal loss and artifacts. It quantifies the average cardiac acceleration and deceleration (AC/DC) capacity. OBJECTIVE: The aims of the study were: (1) to investigate AC/DC in ovine fetuses exposed to acute hypoxic-acidemic insult; (2) to explore the relation between AC/DC and acid-base balance; and (3) to evaluate the influence of FHR decelerations and specific PRSA parameters on AC/DC computation. METHODS: Repetitive umbilical cord occlusions (UCOs) were applied in 9 pregnant near-term sheep to obtain three phases of MILD, MODERATE, and SEVERE hypoxic-acidemic insult. Acid-base balance was sampled and fetal ECGs continuously recorded. AC/DC were calculated: (1) for a spectrum of T values (T = 1/50 beats; the parameter limits the range of oscillations detected by PRSA); (2) on entire series of fetal RR intervals or on "stable" series that excluded FHR decelerations caused by UCOs. RESULTS: AC and DC progressively increased with UCOs phases (MILD vs. MODERATE and MODERATE vs. SEVERE, p<0.05 for DC [Formula: see text] = 2-5, and AC [Formula: see text] = 1-3). The time evolution of AC/DC correlated to acid-base balance (0.4<[Formula: see text]<0.9, p<0.05) with the highest [Formula: see text] for [Formula: see text]. PRSA was not independent from FHR decelerations caused by UCOs. CONCLUSIONS: This is the first in-vivo evaluation of PRSA on FHR analysis. In the presence of acute hypoxic-acidemia we found increasing values of AC/DC suggesting an activation of ANS. This correlation was strongest on time scale dominated by parasympathetic modulations. We identified the best performing [Formula: see text] parameters ([Formula: see text]), and found that AC/DC computation is not independent from FHR decelerations. These findings establish the basis for future clinical studies. PMID- 25141130 TI - A long-term cultivation of an anaerobic methane-oxidizing microbial community from deep-sea methane-seep sediment using a continuous-flow bioreactor. AB - Anaerobic oxidation of methane (AOM) in marine sediments is an important global methane sink, but the physiological characteristics of AOM-associated microorganisms remain poorly understood. Here we report the cultivation of an AOM microbial community from deep-sea methane-seep sediment using a continuous-flow bioreactor with polyurethane sponges, called the down-flow hanging sponge (DHS) bioreactor. We anaerobically incubated deep-sea methane-seep sediment collected from the Nankai Trough, Japan, for 2,013 days in the bioreactor at 10 degrees C. Following incubation, an active AOM activity was confirmed by a tracer experiment using 13C-labeled methane. Phylogenetic analyses demonstrated that phylogenetically diverse Archaea and Bacteria grew in the bioreactor. After 2,013 days of incubation, the predominant archaeal components were anaerobic methanotroph (ANME)-2a, Deep-Sea Archaeal Group, and Marine Benthic Group-D, and Gammaproteobacteria was the dominant bacterial lineage. Fluorescence in situ hybridization analysis showed that ANME-1 and -2a, and most ANME-2c cells occurred without close physical interaction with potential bacterial partners. Our data demonstrate that the DHS bioreactor system is a useful system for cultivating fastidious methane-seep-associated sedimentary microorganisms. PMID- 25141133 TI - Distribution and determinants of non communicable diseases among elderly Uyghur ethnic group in Xinjiang, China. AB - BACKGROUND: Non-communicable diseases (NCDs) are showing an increasing trend globally as well as in China. Elderly population are more prone to these NCDs. Situation in China is worse owing to the higher proportion of geriatric population. Burden of NCDs and the role of their socio-demographic and behavioral predictors among these elderly and more so among the ethnic minority groups among them, need to be investigated specifically, owing to their distinct genetic background, lifestyles and behavior. METHODS: A cross-sectional study was conducted among 1329 randomly selected persons of Uyghur ethnicity, aged 60 years or more in Xinjiang, the largest administrative division in China to measure the burden of NCDs, understand the distribution of socio-demographic, behavioral and life event-related potential correlates of them and to estimate the association of the NCDs with these correlates. RESULTS: Among these participants 54.2% were female, 86.8% were married and more than half had only attended elementary school or less. 41.46% was suffering from at least one NCD. 20.22% had one NCD, 12.11% had two and 8.58% had three or more. 27.3% had hypertension, 4.06% had diabetes, 6.02% had hyperlipidemia, 7.37% had angina, 14.52% had cardiovascular diseases, 11.59% had any kind of cancers and 9.78% had chronic obstructive pulmonary diseases. Rural residents (OR = 1.45, 95% CI: 1.17-1.80, AOR = 2.00, 95% CI: 1.53 2.61) and current smokers had higher odds of having more NCDs (AOR = 1.53, 95% CI: 1.00-2.34). Additionally not being satisfied with current life, not being able to take care of self in daily life, currently not being involved in farm work, less intake of fresh vegetables, fruits and garlic, too less or too much salt intake, not having hobbies were found to be positively associated with having more NCDs. CONCLUSION: Implementation of effective intervention strategies to promote healthy life styles among the Uyghur elderly population of China seems urgent. PMID- 25141134 TI - Restrained and external-emotional eating patterns in young overweight children results of the Ulm Birth Cohort Study. AB - Childhood obesity is one of the greatest public health challenges in Western countries. Abnormal eating behavior is thought to be a developmental trajectory to obesity. The Eating Pattern Inventory for Children (EPI-C) has not been used for children as young as eight years, and possible associations with body weight have not yet been established. Five hundred and twenty-one children of the Ulm Birth Cohort Study (UBCS; age eight) filled out the EPI-C and BMI was assessed. Adequacy of the scales was tested with confirmatory factor analysis and a MANOVA and cluster analysis established associations between eating patterns and BMI. The factor structure of the EPI-C was confirmed (GFI = .968) and abnormal eating behavior was associated with overweight (chi(2)(8) =79.29, p<.001). The EPI-C is a valid assessment tool in this young age group. Overweight children consciously restrain their eating. PMID- 25141135 TI - GBA2-encoded beta-glucosidase activity is involved in the inflammatory response to Pseudomonas aeruginosa. AB - Current anti-inflammatory strategies for the treatment of pulmonary disease in cystic fibrosis (CF) are limited; thus, there is continued interest in identifying additional molecular targets for therapeutic intervention. Given the emerging role of sphingolipids (SLs) in various respiratory disorders, including CF, drugs that selectively target the enzymes associated with SL metabolism are under development. Miglustat, a well-characterized iminosugar-based inhibitor of beta-glucosidase 2 (GBA2), has shown promise in CF treatment because it reduces the inflammatory response to infection by P. aeruginosa and restores F508del-CFTR chloride channel activity. This study aimed to probe the molecular basis for the anti-inflammatory activity of miglustat by examining specifically the role of GBA2 following the infection of CF bronchial epithelial cells by P. aeruginosa. We also report the anti-inflammatory activity of another potent inhibitor of GBA2 activity, namely N-(5-adamantane-1-yl-methoxy)pentyl)-deoxynojirimycin (Genz 529648). In CF bronchial cells, inhibition of GBA2 by miglustat or Genz-529648 significantly reduced the induction of IL-8 mRNA levels and protein release following infection by P. aeruginosa. Hence, the present data demonstrate that the anti-inflammatory effects of miglustat and Genz-529648 are likely exerted through inhibition of GBA2. PMID- 25141136 TI - Silyl phosphorus and nitrogen donor chelates for homogeneous ortho borylation catalysis. AB - Ir catalysts supported by bidentate silyl ligands that contain P- or N-donors are shown to effect ortho borylations for a range of substituted aromatics. The substrate scope is broad, and the modular ligand synthesis allows for flexible catalyst design. PMID- 25141137 TI - The clinical and bacteriological factors for optimal levofloxacin-containing triple therapy in second-line Helicobacter pylori eradication. AB - Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily). They were prescribed with either a 10-day (group A) or 14-day (group B) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days) by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI] = 63.9-85.3%) and 90.5% (95% CI = 84.5-98.1%), respectively in the per protocol analysis (P = 0.008 in the per protocol analysis) and 67.1% (95% CI = 56.6-78.5%) and 84.8% (95% CI = 76.8-93.4%), respectively, in the intention-to-treat analysis (P = 0.009). The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14) but it dropped to 12.5% (1/8) when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful treatment. This study suggests that tailored levofloxacin-containing therapy should be administered only for patients with susceptible strains because it can achieve >90% success rates. PMID- 25141138 TI - Quantitative estimation of renal function with dynamic contrast-enhanced MRI using a modified two-compartment model. AB - OBJECTIVE: To establish a simple two-compartment model for glomerular filtration rate (GFR) and renal plasma flow (RPF) estimations by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: A total of eight New Zealand white rabbits were included in DCE-MRI. The two-compartment model was modified with the impulse residue function in this study. First, the reliability of GFR measurement of the proposed model was compared with other published models in Monte Carlo simulation at different noise levels. Then, functional parameters were estimated in six healthy rabbits to test the feasibility of the new model. Moreover, in order to investigate its validity of GFR estimation, two rabbits underwent acute ischemia surgical procedure in unilateral kidney before DCE-MRI, and pixel-wise measurements were implemented to detect the cortical GFR alterations between normal and abnormal kidneys. RESULTS: The lowest variability of GFR and RPF measurements were found in the proposed model in the comparison. Mean GFR was 3.03+/-1.1 ml/min and mean RPF was 2.64+/-0.5 ml/g/min in normal animals, which were in good agreement with the published values. Moreover, large GFR decline was found in dysfunction kidneys comparing to the contralateral control group. CONCLUSION: Results in our study demonstrate that measurement of renal kinetic parameters based on the proposed model is feasible and it has the ability to discriminate GFR changes in healthy and diseased kidneys. PMID- 25141139 TI - Programmed life span in the context of evolvability. AB - Population turnover is necessary for progressive evolution. In the context of a niche with fixed carrying capacity, aging contributes to the rate of population turnover. Theoretically, a population in which death is programmed on a fixed schedule can evolve more rapidly than one in which population turnover is left to a random death rate. Could aging evolve on this basis? Quantitative realization of this idea is problematic, since the short-term individual fitness cost is likely to eliminate any hypothetical gene for programmed death before the long term benefit can be realized. In 2011, one of us proposed the first quantitative model based on this mechanism that robustly evolves a finite, programmed life span. That model was based on a viscous population in a rapidly changing environment. Here, we strip this model to its essence and eliminate the assumption of environmental change. We conclude that there is no obvious way in which this model is unrealistic, and that it may indeed capture an important principle of nature's workings. We suggest aging may be understood within the context of the emerging science of evolvability. PMID- 25141140 TI - Haplodiploidy and the evolution of eusociality: worker revolution. AB - Hamilton suggested that inflated relatedness between sisters promotes the evolution of eusociality in haplodiploid populations. Trivers and Hare observed that for this to occur, workers have to direct helping preferentially toward the production of sisters. Building on this, they proposed two biological scenarios whereby haplodiploidy could act to promote the evolution of eusociality: (a) workers biasing the sex allocation of the queen's brood toward females and (b) workers replacing the queen's sons with their own sons. This "worker revolution," whereby the worker class seizes control of sex allocation and reproduction, is expected to lead to helping being promoted in worker-controlled colonies. Here, we use a kin-selection approach to model the two scenarios suggested by Trivers and Hare. We show that (1) worker control of sex allocation may promote helping, but this effect is likely to be weak and short lived; and (2) worker reproduction tends to inhibit rather than promote helping. Furthermore, the promotion of helping is reduced by a number of biologically likely factors, including the presence of workers increasing colony productivity, workers being unmated, and worker control of sex allocation being underpinned by many loci each having a small effect. Overall, our results suggest that haplodiploidy has had a negligible influence on the evolution of eusociality. PMID- 25141141 TI - Unmatedness promotes the evolution of helping more in diplodiploids than in haplodiploids. AB - The predominance of haplodiploidy (where males develop from unfertilized haploid eggs and females from fertilized diploid eggs) among eusocial species has inspired a body of research that focuses on the possible role of relatedness asymmetries in the evolution of helping and eusociality. Previous theory has shown that in order for relatedness asymmetries to favor the evolution of helping, there needs to be variation in sex ratios among nests in the population (i.e., split sex ratios). In haplodiploid species, unmated females can produce a brood of all males, and this is considered the most likely mechanism for split sex ratios at the origin of helping. In contrast, in diploidiploids unmatedness means total reproductive failure. We compare the effect of unmatedness on selection for male and female helping in haplodiploids and diplodiploids. We show that in haplodiploids, unmatedness promotes helping in females but not in males within the empirical range. In diplodiploids, unmatedness promotes helping by both sexes, and the effect is stronger than in haplodiploids, all else being equal. Our study highlights the need to consider interactions between ecological and genetic factors in the evolution of helping and eusociality. PMID- 25141142 TI - Male bias in distributions of additive genetic, residual, and phenotypic variances of shared traits. AB - Despite a shared genetic architecture between males and females, sexual differences are widespread. The extent of this shared genetic architecture, reflected in the intersexual genetic correlation, has previously been correlated with the extent of phenotypic sexual dimorphism in shared traits. However, the magnitude of the difference in sex-specific additive genetic variances may also fuel sexual dimorphism. To explore the correlation between additive genetic variance dimorphism and phenotypic dimorphism, we conducted a literature search. We targeted traits expressed in both sexes and excluded sex-limited traits. The mean difference between the sexes in additive genetic variance was not significantly different from 0. However, the distribution of the sexual difference in additive genetic variance had a significant male-biased skew. This pattern persists even after removing traits explicitly related to reproduction. Furthermore, male traits had more residual and phenotypic variance than homologous female traits (as measured by both the mean and the skew), and this difference was not necessarily due to the difference between sexual traits and nonsexual traits. We found no evidence that sex chromosome system could explain sex differences in additive genetic, nonadditive genetic, or phenotypic variances. Finally, we found a significant correlation between the extent of sexual dimorphism in additive genetic variances and the extent of phenotypic sexual dimorphism. Understanding why traits have sex-specific patterns of variation awaits further investigation. PMID- 25141143 TI - Plant size, sexual selection, and the evolution of protandry in dioecious plants. AB - It is frequently observed that males of dioecious plant species flower earlier in the season than females, although the generality of this pattern has not been quantified. One hypothesis for earlier male flowering is that females require more time for resource acquisition before reproduction; another is that selection for access to unfertilized ovules favors early-flowering males. Here I show that protandry is indeed the usual pattern in dioecious plants--males typically initiate flowering before females--and I propose a new hypothesis to explain this pattern. In many natural plant populations, individuals that begin flowering early are larger and--in the case of females or hermaphrodites--therefore more fecund. When this population-level seasonal decline in size is included in simulations of flowering time evolution in a dioecious plant, males evolve earlier flowering onset than females. Correlations between size (or condition) and reproductive phenology are widespread and likely contribute to the prevalence of protandry in both plants and animals, but their importance seems to have been overlooked by botanists. I suggest that sexual selection (specifically, male-male competition for access to high-quality ovules) may play a more important role in the evolution of flowering phenology than has previously been recognized. PMID- 25141144 TI - Asynchrony of seasons: genetic differentiation associated with geographic variation in climatic seasonality and reproductive phenology. AB - Many organisms exhibit distinct breeding seasons tracking food availability. If conspecific populations inhabit areas that experience different temporal cycles in food availability spurred by variation in precipitation regimes, then they should display asynchronous breeding seasons. Thus, such populations might exhibit a temporal barrier to gene flow, which may potentially promote genetic differentiation. We test a central prediction of this hypothesis, namely, that individuals living in areas with more asynchronous precipitation regimes should be more genetically differentiated than individuals living in areas with more similar precipitation regimes. Using mitochondrial DNA sequences, climatic data, and geographical/ecological distances between individuals of 57 New World bird species mostly from the tropics, we examined the effect of asynchronous precipitation (a proxy for asynchronous resource availability) on genetic differentiation. We found evidence for a positive and significant cross-species effect of precipitation asynchrony on genetic distance after accounting for geographical/ecological distances, suggesting that current climatic conditions may play a role in population differentiation. Spatial asynchrony in climate may thus drive evolutionary divergence in the absence of overt geographic barriers to gene flow; this mechanism contrasts with those invoked by most models of biotic diversification emphasizing physical or ecological changes to the landscape as drivers of divergence. PMID- 25141145 TI - Metabolism and the rise of fungus cultivation by ants. AB - Most ant colonies are comprised of workers that cooperate to harvest resources and feed developing larvae. Around 50 million years ago (MYA), ants of the attine lineage adopted an alternative strategy, harvesting resources used as compost to produce fungal gardens. While fungus cultivation is considered a major breakthrough in ant evolution, the associated ecological consequences remain poorly understood. Here, we compare the energetics of attine colony-farms and ancestral hunter-gatherer colonies using metabolic scaling principles within a phylogenetic context. We find two major energetic transitions. First, the earliest lower-attine farmers transitioned to lower mass-specific metabolic rates while shifting significant fractions of biomass from ant tissue to fungus gardens. Second, a transition 20 MYA to specialized cultivars in the higher attine clade was associated with increased colony metabolism (without changes in garden fungal content) and with metabolic scaling nearly identical to hypometry observed in hunter-gatherer ants, although only the hunter-gatherer slope was distinguishable from isometry. Based on these evolutionary transitions, we propose that shifting living-tissue storage from ants to fungal mutualists provided energetic storage advantages contributing to attine diversification and outline critical assumptions that, when tested, will help link metabolism, farming efficiency, and colony fitness. PMID- 25141146 TI - Nonautosomal genetic variation in carotenoid coloration. AB - Carotenoid-based coloration plays an important role in signaling, is often sexually dimorphic, and is potentially subject to directional and/or sex-specific selection. To understand the evolutionary dynamics of such color traits, it is essential to quantify patterns of inheritance, yet nonautosomal sources of genetic variation are easily overlooked by classical heritability analyses. Carotenoid metabolism has recently been linked to mitochondria, highlighting the potential for color variation to be explained by cytoplasmically inherited factors. In this study, we used quantitative genetic animal models to estimate the importance of mitochondrial and sex chromosome-linked sources of genetic variation in coloration in two songbird populations in which dietary carotenoids are either unmodified (great tit plumage) or metabolized into alternative color forms (zebra finch beak). We found no significant Z-linked genetic variance in great tit plumage coloration, while zebra finch beak coloration exhibited significant W linkage and cytoplasmic inheritance. Our results support cytoplasmic inheritance of color in the zebra finch, a trait based on endogenously metabolized carotenoids, and demonstrate the potential for nonautosomal sources to account for a considerable share of genetic variation in coloration. Although often overlooked, such nonautosomal genetic variation exhibits sex-dependent patterns of inheritance and potentially influences the evolution of sexual dichromatism. PMID- 25141147 TI - Nutrient limitation and physiology mediate the fine-scale (de)coupling of biogeochemical cycles. AB - Nutrients in the environment are coupled over broad timescales (days to seasons) when organisms add or withdraw multiple nutrients simultaneously and in ratios that are roughly constant. But at finer timescales (seconds to days), nutrients become decoupled if physiological traits such as nutrient storage limits, circadian rhythms, or enzyme kinetics cause one nutrient to be processed faster than another. To explore the interactions among these coupling and decoupling mechanisms, we introduce a model in which organisms process resources via uptake, excretion, growth, respiration, and mortality according to adjustable trait parameters. The model predicts that uptake can couple the input of one nutrient to the export of another in a ratio reflecting biological demand stoichiometry, but coupling occurs only when the input nutrient is limiting. Temporal nutrient coupling may, therefore, be a useful indicator of ecosystem limitation status. Fine-scale patterns of nutrient coupling are further modulated by, and potentially diagnostic of, physiological traits governing growth, uptake, and internal nutrient storage. Together, limitation status and physiological traits create a complex and informative relationship between nutrient inputs and exports. Understanding the mechanisms behind that relationship could enrich interpretations of fine-scale time-series data such as those now emerging from in situ solute sensors. PMID- 25141148 TI - Pathogen growth in insect hosts: inferring the importance of different mechanisms using stochastic models and response-time data. AB - Pathogen population dynamics within individual hosts can alter disease epidemics and pathogen evolution, but our understanding of the mechanisms driving within host dynamics is weak. Mathematical models have provided useful insights, but existing models have only rarely been subjected to rigorous tests, and their reliability is therefore open to question. Most models assume that initial pathogen population sizes are so large that stochastic effects due to small population sizes, so-called demographic stochasticity, are negligible, but whether this assumption is reasonable is unknown. Most models also assume that the dynamic effects of a host's immune system strongly affect pathogen incubation times or "response times," but whether such effects are important in real host pathogen interactions is likewise unknown. Here we use data for a baculovirus of the gypsy moth to test models of within-host pathogen growth. By using Bayesian statistical techniques and formal model-selection procedures, we are able to show that the response time of the gypsy moth virus is strongly affected by both demographic stochasticity and a dynamic response of the host immune system. Our results imply that not all response-time variability can be explained by host and pathogen variability, and that immune system responses to infection may have important effects on population-level disease dynamics. PMID- 25141149 TI - Effects of temperature on intraspecific competition in ectotherms. AB - Understanding how temperature influences population regulation through its effects on intraspecific competition is an important question for which there is currently little theory or data. Here we develop a theoretical framework for elucidating temperature effects on competition that integrates mechanistic descriptions of life-history trait responses to temperature with population models that realistically capture the variable developmental delays that characterize ectotherm life cycles. This framework yields testable comparative predictions about how intraspecific competition affects reproduction, development, and mortality under alternative hypotheses about the temperature dependence of competition. The key finding is that ectotherm population regulation in seasonal environments depends crucially on the mechanisms by which temperature affects competition. When competition is strongest at temperatures optimal for reproduction, effects of temperature and competition act antagonistically, leading to more complex dynamics than when competition is temperature independent. When the strength of competition increases with temperature past the optimal temperature for reproduction, effects of temperature and competition act synergistically, leading to dynamics qualitatively similar to those when competition is temperature independent. Paradoxically, antagonistic effects yield a higher population floor despite greater fluctuations. These findings have important implications for predicting effects of climate warming on population regulation. Synergistic effects of temperature and competition can predispose populations to stochastic extinction by lowering minimum population sizes, while antagonistic effects can increase the potential for population outbreaks through greater fluctuations in abundance. PMID- 25141150 TI - Sex-specific patterns of aging in sexual ornaments and gametes. AB - Sex differences in age-dependent mortality and reproductive success are predicted to drive the evolution of sexually dimorphic patterns of reproductive investment over life. However, this prediction has not been fully explored because it is difficult to measure primary and secondary sexual traits over the life spans of males and females. Here we studied a population of fowl, Gallus gallus, to gain longitudinal data on a sexual ornament (the comb), quantity of gametes produced, and gamete quality (sperm velocity and egg mass) of males and females. Our results reveal pronounced differences between the sexes in age-specific patterns of reproductive investment. In males, comb size decreased linearly with age, high sperm quality early in life was associated with reduced sperm quality late in life, and high sperm production was related to early death. In contrast, female comb size and egg mass were maximized at intermediate ages, and fecundity was independent of life span. Finally, the way traits were related in males did not change over life, whereas in females the association between fecundity and comb size changed from positive to negative over the lifetime of a female, indicating that aging may lead to trade-offs in investment between traits in females. These results show that males and females differ in reproductive investment with age, in terms of both the expression of individual traits and their phenotypic covariance. PMID- 25141151 TI - Ecdysteroid hormones link the juvenile environment to alternative adult life histories in a seasonal insect. AB - The conditional expression of alternative life strategies is a widespread feature of animal life and a pivotal adaptation to life in seasonal environments. To optimally match suites of traits to seasonally changing ecological opportunities, animals living in seasonal environments need mechanisms linking information on environmental quality to resource allocation decisions. The butterfly Bicyclus anynana expresses alternative adult life histories in the alternating wet and dry seasons of its habitat as endpoints of divergent developmental pathways triggered by seasonal variation in preadult temperature. Pupal ecdysteroid hormone titers are correlated with the seasonal environment, but whether they play a functional role in coordinating the coupling of adult traits in the alternative life histories is unknown. Here, we show that manipulating pupal ecdysteroid levels is sufficient to mimic in direction and magnitude the shifts in adult reproductive resource allocation normally induced by seasonal temperature. Crucially, this allocation shift is accompanied by changes in ecologically relevant traits, including timing of reproduction, life span, and starvation resistance. Together, our results support a functional role for ecdysteroids during development in mediating strategic reproductive investment decisions in response to predictive indicators of environmental quality. This study provides a physiological mechanism for adaptive developmental plasticity, allowing organisms to cope with variable environments. PMID- 25141152 TI - Cyclic decidualization of the human endometrium in reproductive health and failure. AB - Decidualization denotes the transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunoprivileged matrix essential for embryo implantation and placental development. In contrast to most mammals, decidualization of the human endometrium does not require embryo implantation. Instead, this process is driven by the postovulatory rise in progesterone levels and increasing local cAMP production. In response to falling progesterone levels, spontaneous decidualization causes menstrual shedding and cyclic regeneration of the endometrium. A growing body of evidence indicates that the shift from embryonic to maternal control of the decidual process represents a pivotal evolutionary adaptation to the challenge posed by invasive and chromosomally diverse human embryos. This concept is predicated on the ability of decidualizing stromal cells to respond to individual embryos in a manner that either promotes implantation and further development or facilitates early rejection. Furthermore, menstruation and cyclic regeneration involves stem cell recruitment and renders the endometrium intrinsically capable of adapting its decidual response to maximize reproductive success. Here we review the endocrine, paracrine, and autocrine cues that tightly govern this differentiation process. In response to activation of various signaling pathways and genome-wide chromatin remodeling, evolutionarily conserved transcriptional factors gain access to the decidua-specific regulatory circuitry. Once initiated, the decidual process is poised to transit through distinct phenotypic phases that underpin endometrial receptivity, embryo selection, and, ultimately, resolution of pregnancy. We discuss how disorders that subvert the programming, initiation, or progression of decidualization compromise reproductive health and predispose for pregnancy failure. PMID- 25141154 TI - Surfactant-assisted synthesis of Fe2O3 nanoparticles and F-doped carbon modification toward an improved Fe3O4@CFx/LiNi0.5Mn1.5O4 battery. AB - A simple surfactant-assisted reflux method was used in this study for the synthesis of cocklebur-shaped Fe2O3 nanoparticles (NPs). With this strategy, a series of nanostructured Fe2O3 NPs with a size distribution ranging from 20 to 120 nm and a tunable surface area were readily controlled by varying reflux temperature and the type of surfactant. Surfactants such as cetyltrimethylammonium bromide (CTAB), polyvinylpyrrolidone (PVP), poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (F127) and sodium dodecyl benzenesulfonate (SDBS) were used to achieve large-scale synthesis of uniform Fe2O3 NPs with a relatively low cost. A new composite of Fe3O4@CFx was prepared by coating the primary Fe2O3 NPs with a layer of F-doped carbon (CFx) with a one-step carbonization process. The Fe3O4@CFx composite was utilized as the anode in a lithium ion battery and exhibited a high reversible capacity of 900 mAh g(-1) at a current density of 100 mA g(-1) over 100 cycles with 95% capacity retention. In addition, a new Fe3O4@CFx/LiNi(0.5)Mn(1.5)O4 battery with a high energy density of 371 Wh kg(-1) (vs cathode) was successfully assembled, and more than 300 cycles were easily completed with 66.8% capacity retention at 100 mA g(-1). Even cycled at the high temperature of 45 degrees C, this full cell also exhibited a relatively high capacity of 91.6 mAh g(-1) (vs cathode) at 100 mA g(-1) and retained 54.6% of its reversible capacity over 50 cycles. Introducing CFx chemicals to modify metal oxide anodes and/or any other cathode is of great interest for advanced energy storage and conversion devices. PMID- 25141156 TI - Unexpected primary reactions for thermolysis of 1,1-diamino-2,2-dinitroethylene (FOX-7) revealed by ab initio calculations. AB - The primary thermolysis reactions of a promising insensitive explosive 1,1 diamino-2,2-dinitroethylene (DADNE, FOX-7) have been studied in the gas phase at a high level of theory (CCSD(T)-F12/aVTZ). Our calculations revealed that none of the conventional reactions (C-NO2 bond fission, nitro-nitrite and nitro-aci-nitro rearrangements) dominate thermolysis of FOX-7. On the contrary, two new decomposition pathways specific for this particular species that commenced with enamino-imino isomerization and intramolecular cyclization were found instead to be more feasible energetically. The activation barriers of these primary isomerization reactions were calculated to be 48.4 and 28.8 kcal/mol, while the activation energies of the overall decomposition pathways are predicted to be ~49 and ~56 kcal/mol, respectively. The new pathways can also be relevant for a wide series of unsaturated hydrocarbons substituted with both nitro- and amino-groups (e.g., triaminotrinitrobenzene, TATB). PMID- 25141153 TI - Sox17 regulates liver lipid metabolism and adaptation to fasting. AB - Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARalpha driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting. PMID- 25141157 TI - Single particle nanomechanics in operando batteries via lensless strain mapping. AB - We reveal three-dimensional strain evolution in situ of a single LiNi0.5Mn1.5O4 nanoparticle in a coin cell battery under operando conditions during charge/discharge cycles with coherent X-ray diffractive imaging. We report direct observation of both stripe morphologies and coherency strain at the nanoscale. Our results suggest the critical size for stripe formation is 50 nm. Surprisingly, the single nanoparticle elastic energy landscape, which we map with femtojoule precision, depends on charge versus discharge, indicating hysteresis at the single particle level. This approach opens a powerful new avenue for studying battery nanomechanics, phase transformations, and capacity fade under operando conditions at the single particle level that will enable profound insight into the nanoscale mechanisms that govern electrochemical energy storage systems. PMID- 25141158 TI - Full antibody primary structure and microvariant characterization in a single injection using transient isotachophoresis and sheathless capillary electrophoresis-tandem mass spectrometry. AB - Here we report the complete characterization of the primary structure of a multimeric glycoprotein in a single analysis by capillary electrophoresis (CE) coupled to mass spectrometry (MS). CE was coupled to electrospray ionization tandem MS by means of a sheathless interface. Transient isotachophoresis (t-ITP) was introduced in this work as an electrokinetically based preconcentration technique, allowing injection of up to 25% of the total capillary volume. Characterization was based on an adapted bottom-up proteomic strategy. Using trypsin as the sole proteolytic enzyme and data from a single injection per considered protein, 100% of the amino acid sequences of four different monoclonal antibodies could be achieved. Furthermore, illustrating the effectiveness and overall capabilities of the technique, the results were possible through identification of peptides without tryptic miscleavages or posttranslational modifications, demonstrating the potency of the technique. In addition to full sequence coverages, posttranslational modifications (PTMs) were simultaneously identified, further demonstrating the capacity of this strategy to structurally characterize glycosylations as well as faint modifications such as asparagine deamidation or aspartic acid isomerization. Together with the exquisite detection sensitivity observed, the contributions of both the CE separation mechanism and selectivity were essential to the result of the characterization with regard to that achieved with conventional MS strategies. The quality of the results indicates that recent improvements in interfacing CE-MS coupling, leading to a considerably improved sensitivity, allows characterization of the primary structure of proteins in a robust and faster manner. Taken together, these results open new research avenues for characterization of proteins through MS. PMID- 25141159 TI - HATCN-based charge recombination layers as effective interconnectors for tandem organic solar cells. AB - A comprehensive understanding of the energy-level alignment at the organic heterojunction interfaces is of paramount importance to optimize the performance of organic solar cells (OSCs). Here, the detailed electronic structures of organic interconnectors, consisting of cesium fluoride-doped 4,7-diphenyl-1,10 phenanthroline and hexaazatriphenylene-hexacarbonitrile (HATCN), have been investigated via in situ photoemission spectroscopy, and their impact on the charge recombination process in tandem OSCs has been identified. The experimental determination shows that the HATCN interlayer plays a significant role in the interface energetics with a dramatic decrease in the reverse built-in potential for electrons and holes from stacked subcells, which is beneficial to the charge recombination between HATCN and the adjacent layer. In accordance with the energy level alignments, the open-circuit voltage of tandem OSC incorporating a HATCN based interconnector is almost 2 times that of a single-cell OSC, revealing the effectiveness of the HATCN-based interconnectors in tandem organic devices. PMID- 25141160 TI - Management of scars: updated practical guidelines and use of silicones. AB - Hypertrophic scars and keloids resulting from surgery, burns, trauma and infection can be associated with substantial physical and psychological distress. Various non-invasive and invasive options are currently available for the prevention and treatment of these scars. Recently, an international multidisciplinary group of 24 experts on scar management (dermatologists; plastic and reconstructive surgeons; general surgeons; physical medicine, rehabilitation and burns specialists; psychosocial and behavioural researchers; epidemiologists; beauticians) convened to update a set of practical guidelines for the prevention and treatment of hypertrophic and keloid scars on the basis of the latest published clinical evidence on existing scar management options. Silicone-based products such as sheets and gels are recommended as the gold standard, first line, non-invasive option for both the prevention and treatment of scars. Other general scar preventative measures include avoiding sun exposure, compression therapy, taping and the use of moisturisers. Invasive treatment options include intralesional injections of corticosteroids and/or 5-fluorouracil, cryotherapy, radiotherapy, laser therapy and surgical excision. All of these options may be used alone or as part of combination therapy. Of utmost importance is the regular re-evaluation of patients every four to eight weeks to evaluate whether additional treatment is warranted. The amount of scar management measures that are applied to each wound depends on the patient's risk of developing a scar and their level of concern about the scar's appearance. The practical advice presented in the current guidelines should be combined with clinical judgement when deciding on the most appropriate scar management measures for an individual patient. PMID- 25141161 TI - Tweets on the road. AB - The pervasiveness of mobile devices, which is increasing daily, is generating a vast amount of geo-located data allowing us to gain further insights into human behaviors. In particular, this new technology enables users to communicate through mobile social media applications, such as Twitter, anytime and anywhere. Thus, geo-located tweets offer the possibility to carry out in-depth studies on human mobility. In this paper, we study the use of Twitter in transportation by identifying tweets posted from roads and rails in Europe between September 2012 and November 2013. We compute the percentage of highway and railway segments covered by tweets in 39 countries. The coverages are very different from country to country and their variability can be partially explained by differences in Twitter penetration rates. Still, some of these differences might be related to cultural factors regarding mobility habits and interacting socially online. Analyzing particular road sectors, our results show a positive correlation between the number of tweets on the road and the Average Annual Daily Traffic on highways in France and in the UK. Transport modality can be studied with these data as well, for which we discover very heterogeneous usage patterns across the continent. PMID- 25141162 TI - Weaning from mechanical ventilation. AB - For many critically ill patients admitted to an intensive care unit, the insertion of an endotracheal tube and the initiation of mechanical ventilation (MV) can be lifesaving procedures. Subsequent patient care often requires intensivists to manage the complex interaction of multiple failing organ systems. The shift in the intensivists' focus toward the discontinuation of MV can thus occur late in the course of critical illness. The dangers of MV, however, make it imperative to wean patients at the earliest possible time. Premature weaning trials, however, trigger significant respiratory distress, which can cause setbacks in the patient's clinical course. Premature extubation is also risky. To reduce delayed weaning and premature extubation, a three-step diagnostic strategy is suggested: measurement of weaning predictors, a trial of unassisted breathing (T-tube trial), and a trial of extubation. Since each step constitutes a diagnostic test, clinicians must not only command a thorough understanding of each test but must also be aware of the principles of clinical decision making when interpreting the information generated by each step. Many difficult aspects of pulmonary pathophysiology encroach on weaning management. Accordingly, weaning commands sophisticated, individualized care. Few other responsibilities of an intensivist require a more analytical effort and carry more promise for improving patient outcome than the application of physiologic principles in the weaning of patients. PMID- 25141163 TI - Prenatal exposure to hyperemesis gravidarum linked to increased risk of psychological and behavioral disorders in adulthood. AB - Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, is characterized by long-term maternal stress, undernutrition and dehydration. While maternal stress and malnutrition of pregnancy are linked to poor neonatal outcome and associated with poor adult health, long-term outcome of fetal exposure to HG has never been explored. The purpose of this study is to determine whether long term emotional and behavioral diagnoses may be associated with fetal exposure to HG. Emotional and behavioral diagnoses of adults born of a pregnancy complicated by HG were compared to diagnoses from non-exposed controls. Offspring exposed to HG in utero were significantly more likely to have a psychological and behavioral disorder (OR = 3.6, P < 0.0001) with diagnoses primarily of depression, bipolar disorder and anxiety. In utero exposure to HG may lead to increased risks of psychological and behavioral disorders in the offspring. PMID- 25141164 TI - Variable placental thickness affects placental functional efficiency independent of other placental shape abnormalities. AB - Our previous work suggests that stressors that impact placental vascular growth result in a deformed chorionic surface shape, which reflects an abnormal placental three-dimensional shape. We propose to use variability of placental disk thickness as a reflector of deviations in placental vascular growth at the finer level of the fetal stems. We hypothesize that increased variability of thickness is associated with abnormal chorionic surface shape, but will be a predictor of reduced placental functional efficiency (smaller baby for a given placental weight) independent of shape. These measures may shed light on the mechanisms linking placental growth to risk of adult disease. The sample was drawn from the Pregnancy, Infection and Nutrition Study. In all, 94.6% of the cohort consented to placental examination. Of the 1023 delivered at term, those previously sectioned by the Pathology Department were excluded, leaving 587 (57%) cases with intact placentas that were sliced and photographed. The chorionic surface shape and the shape of a central randomly oriented placental slice were analyzed and measures were compared using correlation. Lower mean placental disk thickness and more variable disk thickness were each strongly and significantly correlated with deformed chorionic plate shapes. More variable disk thickness was strongly correlated with reduced placental efficiency independent of abnormal chorionic surface shape. Variability of placental disk thickness, simple to measure in a single randomly oriented central slice, may be an easily acquired measure that is an independent indicator of lowered placental efficiency, which may in turn program the infant and result in increased risk for development of adult diseases. PMID- 25141165 TI - Patterns of fetal heart rate response at ~30 weeks gestation predict size at birth. AB - There is evidence that fetal exposure to maternal stress is associated with adverse birth outcomes. Less is known about the association between fetal responses to a stressor and indicators of fetal maturity and developmental outcomes. The purpose of the present study was to determine whether fetal heart rate (FHR) patterns in response to a startling stimulus at ~30 weeks of gestation were associated with gestational age at birth and birth weight. FHR was measured in 156 maternal-fetal dyads following a vibroacoustic stimulus. All pregnancies were singleton intrauterine pregnancies in English-speaking women who were primarily married, middle class, White and at least 18 years of age. Group-based trajectory modeling identified five groups of fetuses displaying distinctive longitudinal trajectories of FHR response to the startling stimulus. The FHR group trajectories were significantly associated with birth weight percentile (P < 0.01) even after controlling for estimated fetal weight at the time of assessment and parity, which are the known factors influencing birth weight (P < 0.01). Post hoc analyses indicated that two groups accounted for the association between FHR patterns and birth weight. The group (n = 23) with the lowest birth weight exhibited an immediate FHR deceleration followed by an immediate acceleration that does not recover. An FHR pattern characterized by immediate and fast acceleration to the peak and a slow discovery to baseline was associated with the highest birth weight. This is the first direct evidence showing that low birth weight and the resulting neurological consequences may have their origins in early fetal development. PMID- 25141166 TI - Aortic growth arrest after preterm birth: a lasting structural change of the vascular tree. AB - Young people who are born very preterm exhibit a narrower arterial tree as compared with people born at term. We hypothesized that such arterial narrowing occurs as a direct result of premature birth. The aim of this study was to compare aortic and carotid artery growth in infants born preterm and at term. Observational and longitudinal cohort study of 50 infants (21 born very preterm, all appropriate for gestational age, 29 controls born at term) was conducted. Diameters of the upper abdominal aorta and common carotid artery were measured with ultrasonography at three months before term, at term and three months after term-equivalent age. At the first assessment, the aortic end-diastolic diameter (aEDD) was slightly larger in very preterm infants as compared with fetal dimensions. Fetal aortic EDD increased by 2.6 mm during the third trimester, whereas very preterm infants exhibited 0.9 mm increase in aEDD during the same developmental period (P < 0.001 for group difference). During the following 3 month period, aortic growth continued unchanged (+0.9 mm) in very preterm infants, whereas postnatal growth in term controls slowed down to +1.3 mm (P < 0.001 v. fetal aortic growth). At the final examination, aEDD was 22% and carotid artery EDD was 14% narrower in infants born preterm compared with controls, also after adjusting for current weight (P < 0.01). Aortic and carotid artery growth is impaired after very preterm birth, resulting in arterial narrowing. Arterial growth failure may be a generalized vascular phenomenon after preterm birth, with implications for cardiovascular morbidity in later life. PMID- 25141167 TI - Maternal undernutrition upregulates apoptosis in offspring nephrogenesis. AB - Maternal undernutrition (MUN) results in growth-restricted newborns with reduced nephron numbers that is associated with increased risk of hypertension and renal disease. The total adult complement of nephrons is set during nephrogenesis suggesting that MUN affects the staged development of nephrons in as yet unknown manner. A possible cause may be the increased renal apoptosis; therefore, we investigated whether apoptotic signaling and cell death were increased in MUN rat kidneys. Pregnant rat dams were fed an ad libitum diet [control] or were 50% food restricted (MUN) starting at embryonic day (E) 10. Male offspring kidneys (n = 5 each, MUN and control) were analyzed for mRNA using quantitative PCR (E20) and for protein expression using Western blotting and immunohistochemistry (E20 and postnatal day 1, P1). Apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Upregulation of pro-apoptotic protein expression was detected at E20 (Fas receptor, caspase 9) and at P1 (caspase 3, Bax). The anti-apoptotic factor Bcl2 was significantly decreased in P1 kidneys. Kidney TUNEL showed apoptotic nuclei significantly increased in the P1 nephrogenic zone (MUN 3.3 + 0.3 v. C 1.6 + 0.5, P = 0.002). The majority of apoptotic nuclei co-localized to mesenchyme and pretubular aggregates in the nephrogenic zone. Differential regulation of apoptosis in mesenchyme and pretubular aggregates following parturition suggests a mechanism for nephropenia in gestational programming of the kidney. PMID- 25141168 TI - The lack of impact of peri-implantation or late gestation nutrient restriction on ovine fetal renal development and function. AB - Unbalanced nutrition during critical windows of development is implicated in determining the susceptibility to hypertension and cardiovascular disease in adult life, but the underlying mechanisms during fetal life have not been fully elucidated. We investigated the effects of moderate nutritional restriction during critical windows in gestation on late gestation fetal sheep growth, cardiovascular and renal renin-angiotensin system function. Ewes were fed 100% nutrient requirements (control), or 40-50% nutrient requirements during the peri implantation period (1-31 days gestation (dGA), PI40 and PI50), or 50% nutrient requirements in late gestation (104-127 dGA). At 125 +/- 2 dGA, fetal cardiovascular and renal function were measured at baseline, and during frusemide, angiotensin II (Ang II), phenylephrine and hypoxia challenges. Maternal undernutrition had no effect on fetal biometry, kidney weight, nephron number, basal cardiovascular function or cardiovascular and renal responses to frusemide. Fetal blood pressure response to Ang II was blunted in PI50 (P < 0.05), but not in PI40 groups. There was no difference between groups in the cardiovascular or endocrine response to hypoxia. The lack of effect of moderate undernutrition within key developmental windows of fetal kidney development on fetal renal structure and function suggests that renal mechanisms do not underlie our previous observations of cardiovascular dysfunction in adulthood following early-life undernutrition. PMID- 25141169 TI - Terpenols as substituents for the diastereoselective formation of enantiomerically pure triple lithium-bridged helicate type-coordination compounds. AB - The terpenols l(-)-borneol, (1S2S3S5R)-3-pinanol, (-)-menthol, and (-)-myrtenol are easily available chiral alcohols for the preparation of enantiomerically pure catechol esters -H2. Those ligands are used for the hierarchical assembly of triple lithium-bridged dinuclear titanium(iv) triscatecholate helicates Li[Li3()6Ti2]. In solution, the dimeric species are in a solvent dependent equilibrium with the monomer Li2[()3Ti]. The equilibrium is studied by (1)H NMR. CD spectroscopy indicates that the configuration at the complex units of the enantiomerically pure dimeric alpha-chiral derivatives Li[Li3()6Ti2] is opposite to the configuration of the monomers Li2[()3Ti]. For the gamma-chiral complex Li2[()3Ti] only a de of 25% is observed and in this case no interpretation of the mechanism of stereocontrol is possible. PMID- 25141171 TI - Whither the Rangeland?: Protection and conversion in California's Rangeland ecosystems. AB - Land use change in rangeland ecosystems is pervasive throughout the western United States with widespread ecological, social and economic implications. In California, rangeland habitats have high biodiversity value, provide significant habitat connectivity and form the foundation for a number of ecosystem services. To comprehensively assess the conservation status of these habitats, we analyzed the extent and drivers of habitat loss and the degree of protection against future loss across a 13.5 M ha study area in California. We analyzed rangeland conversion between 1984 and 2008 using time series GIS data and classified resulting land uses with aerial imagery. In total, over 195,000 hectares of rangeland habitats were converted during this period. The majority of conversions were to residential and associated commercial development (49% of the area converted), but agricultural intensification was surprisingly extensive and diverse (40% across six categories). Voluntary enrollment in an agricultural tax incentive program provided widespread protection from residential and commercial conversions across 37% of the remaining rangeland habitat extent (7.5 M ha), though this program did not protect rangeland from conversion to more intensive agricultural uses. Additionally, 24% of the remaining rangeland was protected by private conservation organizations or public agencies through land or easement ownership while 38% had no protection status at all. By developing a spatial method to analyze the drivers of loss and patterns of protection, this study demonstrates a novel approach to prioritize conservation strategies and implementation locations to avert habitat conversion. We propose that this approach can be used in other ecosystem types, and can serve as a regional conservation baseline assessment to focus strategies to effect widespread, cost effective conservation solutions. PMID- 25141170 TI - Synthesis, biophysical, and pharmacological evaluation of the melanocortin agonist AST3-88: modifications of peptide backbone at Trp 7 position lead to a potent, selective, and stable ligand of the melanocortin 4 receptor (MC4R). AB - The melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors are expressed in the brain and are implicated in the regulation of food intake and energy homeostasis. The endogenous agonist ligands for these receptors (alpha-, beta-, gamma-MSH and ACTH) are linear peptides with limited receptor subtype selectivity and metabolic stability, thus minimizing their use as probes to characterize the overlapping pharmacological and physiological functions of the melanocortin receptor subtypes. In the present study, an engineered template, in which the peptide backbone was modified by a heterocyclic reverse turn mimetic at the Trp(7) residue, was synthesized using solid phase peptide synthesis and characterized by a beta-galactosidase cAMP based reporter gene assay. The functional assay identified a ~5 nM mouse MC4R agonist (AST3-88) with more than 50-fold selectivity over the mMC3R. Biophysical studies (2D (1)H NMR spectroscopy and molecular dynamics) of AST3-88 identified a type VIII beta-turn secondary structure spanning the pharmacophore domain stabilized by the intramolecular interactions between the side chains of the His and Trp residues. Enzymatic studies of AST3-88 revealed enhanced stability of AST3-88 over the alpha-MSH endogenous peptide in rat serum. Upon central administration of AST3-88 into rats, a decreased food intake response was observed. This is the first study to probe the in vivo physiological activity of this engineered peptide-heterocycle template. These findings advance the present knowledge of pharmacophore design for potent, selective, and metabolically stable melanocortin ligands. PMID- 25141172 TI - A direct projection from mouse primary visual cortex to dorsomedial striatum. AB - The mammalian striatum receives inputs from many cortical areas, but the existence of a direct axonal projection from the primary visual cortex (V1) is controversial. In this study we use anterograde and retrograde tracing techniques to demonstrate that V1 directly innervates a topographically defined longitudinal strip of dorsomedial striatum in mice. We find that this projection forms functional excitatory synapses with direct and indirect pathway striatal projection neurons (SPNs) and engages feed-forward inhibition onto these cells. Importantly, stimulation of V1 afferents is sufficient to evoke phasic firing in SPNs. These findings therefore identify a striatal region that is functionally innervated by V1 and suggest that early visual processing may play an important role in striatal-based behaviors. PMID- 25141173 TI - Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis. AB - Benzimidazole drugs lansoprazole and omeprazole are used for treatment of various gastrointestinal pathologies. Both compounds cause drug-drug interactions because they activate aryl hydrocarbon receptor and induce CYP1A genes. In the current paper, we examined the effects of lansoprazole and omeprazole enantiomers on the expression of key drug-metabolizing enzyme CYP3A4 in human hepatocytes and human cancer cell lines. Lansoprazole enantiomers, but not omeprazole, were equipotent inducers of CYP3A4 mRNA in HepG2 cells. All forms (S-, R-, rac-) of lansoprazole and omeprazole induced CYP3A4 mRNA and protein in human hepatocytes. The quantitative profiles of CYP3A4 induction by individual forms of lansoprazole and omeprazole exerted enantiospecific patterns. Lansoprazole dose-dependently activated pregnane X receptor PXR in gene reporter assays, and slightly modulated rifampicin-inducible PXR activity, with similar potency for each enantiomer. Omeprazole dose-dependently activated PXR and inhibited rifampicin-inducible PXR activity. The effects of S-omeprazole were much stronger as compared to those of R-omeprazole. All forms of lansoprazole, but not omeprazole, slightly activated glucocorticoid receptor and augmented dexamethasone-induced GR transcriptional activity. Omeprazole and lansoprazole influenced basal and ligand inducible expression of tyrosine aminotransferase, a GR-target gene, in HepG2 cells and human hepatocytes. Overall, we demonstrate here that omeprazole and lansoprazole enantiomers induce CYP3A4 in HepG2 cells and human hepatocytes. The induction comprises differential interactions of omeprazole and lansoprazole with transcriptional regulators PXR and GR, and some of the effects were enantiospecific. The data presented here might be of toxicological and clinical importance, since the effects occurred in therapeutically relevant concentrations. PMID- 25141175 TI - A DGT technique for plutonium bioavailability measurements. AB - The toxicity of heavy metals in natural waters is strongly dependent on the local chemical environment. Assessing the bioavailability of radionuclides predicts the toxic effects to aquatic biota. The technique of diffusive gradients in thin films (DGT) is largely exploited for bioavailability measurements of trace metals in waters. However, it has not been applied for plutonium speciation measurements yet. This study investigates the use of DGT technique for plutonium bioavailability measurements in chemically different environments. We used a diffusion cell to determine the diffusion coefficients (D) of plutonium in polyacrylamide (PAM) gel and found D in the range of 2.06-2.29 * 10(-6) cm(2) s( 1). It ranged between 1.10 and 2.03 * 10(-6) cm(2) s(-1) in the presence of fulvic acid and in natural waters with low DOM. In the presence of 20 ppm of humic acid of an organic-rich soil, plutonium diffusion was hindered by a factor of 5, with a diffusion coefficient of 0.50 * 10(-6) cm(2) s(-1). We also tested commercially available DGT devices with Chelex resin for plutonium bioavailability measurements in laboratory conditions and the diffusion coefficients agreed with those from the diffusion cell experiments. These findings show that the DGT methodology can be used to investigate the bioaccumulation of the labile plutonium fraction in aquatic biota. PMID- 25141174 TI - Molecular investigations of protriptyline as a multi-target directed ligand in Alzheimer's disease. AB - Alzheimer's disease (AD) is a complex neurodegenerative disorder involving multiple cellular and molecular processes. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies. The repositioning of existing non toxic drugs could dramatically reduce the time and costs involved in developmental and clinical trial stages. In this study, preliminary screening of 140 FDA approved nervous system drugs by docking suggested the viability of the tricyclic group of antidepressants against three major AD targets, viz. Acetylcholinesterase (AChE), beta-secretase (BACE-1), and amyloid beta (Abeta) aggregation, with one member, protriptyline, showing highest inhibitory activity. Detailed biophysical assays, together with isothermal calorimetry, fluorescence quenching experiments, kinetic studies and atomic force microscopy established the strong inhibitory activity of protriptyline against all three major targets. The molecular basis of inhibition was supported with comprehensive molecular dynamics simulations. Further, the drug inhibited glycation induced amyloid aggregation, another important causal factor in AD progression. This study has led to the discovery of protriptyline as a potent multi target directed ligand and established its viability as a promising candidate for AD treatment. PMID- 25141176 TI - Probing the spatial organization of bacteriochlorophyll C by solid-state nuclear magnetic resonance. AB - Green sulfur bacteria, which live in extremely low-light environments, use chlorosomes to harvest light. A chlorosome is the most efficient, and arguably the simplest, light-harvesting antenna complex, which contains hundreds of thousands of densely packed bacteriochlorophylls (BChls). To harvest light efficiently, BChls in a chlorosome form supramolecular aggregates; thus, it is of great interest to determine the organization of the BChls in a chlorosome. In this study, we conducted a (13)C solid-state nuclear magnetic resonance and Mg K edge X-ray absorption analysis of chlorosomes from wild-type Chlorobaculum tepidum. The X-ray absorption results indicated that the coordination number of the Mg in the chlorosome must be >4, providing evidence that electrostatic interactions formed between the Mg of a BChl and the carbonyl group or the hydroxyl group of the neighboring BChl molecule. According to the intermolecular distance constraints obtained on the basis of (13)C homonuclear dipolar correlation spectroscopy, we determined that the molecular assembly of BChls is dimer-based and that the hydrogen bonds among the BChls are less extensive than commonly presumed because of the twist in the orientation of the BChl dimers. This paper also reports the first (13)C homonuclear correlation spectrum acquired for carotenoids and lipids-which are minor, but crucial, components of chlorosomes-extracted from wild-type Cba. tepidum. PMID- 25141177 TI - Comparative population genomics in animals uncovers the determinants of genetic diversity. AB - Genetic diversity is the amount of variation observed between DNA sequences from distinct individuals of a given species. This pivotal concept of population genetics has implications for species health, domestication, management and conservation. Levels of genetic diversity seem to vary greatly in natural populations and species, but the determinants of this variation, and particularly the relative influences of species biology and ecology versus population history, are still largely mysterious. Here we show that the diversity of a species is predictable, and is determined in the first place by its ecological strategy. We investigated the genome-wide diversity of 76 non-model animal species by sequencing the transcriptome of two to ten individuals in each species. The distribution of genetic diversity between species revealed no detectable influence of geographic range or invasive status but was accurately predicted by key species traits related to parental investment: long-lived or low-fecundity species with brooding ability were genetically less diverse than short-lived or highly fecund ones. Our analysis demonstrates the influence of long-term life history strategies on species response to short-term environmental perturbations, a result with immediate implications for conservation policies. PMID- 25141178 TI - Diabetes recovery by age-dependent conversion of pancreatic delta-cells into insulin producers. AB - Total or near-total loss of insulin-producing beta-cells occurs in type 1 diabetes. Restoration of insulin production in type 1 diabetes is thus a major medical challenge. We previously observed in mice in which beta-cells are completely ablated that the pancreas reconstitutes new insulin-producing cells in the absence of autoimmunity. The process involves the contribution of islet non beta-cells; specifically, glucagon-producing alpha-cells begin producing insulin by a process of reprogramming (transdifferentiation) without proliferation. Here we show the influence of age on beta-cell reconstitution from heterologous islet cells after near-total beta-cell loss in mice. We found that senescence does not alter alpha-cell plasticity: alpha-cells can reprogram to produce insulin from puberty through to adulthood, and also in aged individuals, even a long time after beta-cell loss. In contrast, before puberty there is no detectable alpha cell conversion, although beta-cell reconstitution after injury is more efficient, always leading to diabetes recovery. This process occurs through a newly discovered mechanism: the spontaneous en masse reprogramming of somatostatin-producing delta-cells. The juveniles display 'somatostatin-to insulin' delta-cell conversion, involving dedifferentiation, proliferation and re expression of islet developmental regulators. This juvenile adaptability relies, at least in part, upon the combined action of FoxO1 and downstream effectors. Restoration of insulin producing-cells from non-beta-cell origins is thus enabled throughout life via delta- or alpha-cell spontaneous reprogramming. A landscape with multiple intra-islet cell interconversion events is emerging, offering new perspectives for therapy. PMID- 25141179 TI - Saturation editing of genomic regions by multiplex homology-directed repair. AB - Saturation mutagenesis--coupled to an appropriate biological assay--represents a fundamental means of achieving a high-resolution understanding of regulatory and protein-coding nucleic acid sequences of interest. However, mutagenized sequences introduced in trans on episomes or via random or "safe-harbour" integration fail to capture the native context of the endogenous chromosomal locus. This shortcoming markedly limits the interpretability of the resulting measurements of mutational impact. Here, we couple CRISPR/Cas9 RNA-guided cleavage with multiplex homology-directed repair using a complex library of donor templates to demonstrate saturation editing of genomic regions. In exon 18 of BRCA1, we replace a six-base-pair (bp) genomic region with all possible hexamers, or the full exon with all possible single nucleotide variants (SNVs), and measure strong effects on transcript abundance attributable to nonsense-mediated decay and exonic splicing elements. We similarly perform saturation genome editing of a well-conserved coding region of an essential gene, DBR1, and measure relative effects on growth that correlate with functional impact. Measurement of the functional consequences of large numbers of mutations with saturation genome editing will potentially facilitate high-resolution functional dissection of both cis-regulatory elements and trans-acting factors, as well as the interpretation of variants of uncertain significance observed in clinical sequencing. PMID- 25141180 TI - Biological techniques: Edit the genome to understand it. PMID- 25141182 TI - Fabrication of bright and small size semiconducting polymer nanoparticles for cellular labelling and single particle tracking. AB - In this work, we demonstrate a convenient and robust strategy for efficient fabrication of high fluorescence quantum yield (QY, 49.8 +/- 3%) semiconducting polymer nanoparticles (SPNs), with size comparable with semiconductor quantum dots (Qdots). The SPNs were synthesized by co-precipitation of hydrophobic semiconducting polymer together with amphiphilic multidentate polymer. Comprehensive spectroscopic and microscopic characterizations showed that the SPNs possess superior photophysical performance, with excellent fluorescence brightness and reduced photoblinking in contrast with Qdots, as well as good photostability compared to a fluorescent protein of a similar size, phycoerythrin. More importantly, by conjugating membrane biomarkers onto the surface of SPNs, it was found that they were not only suitable for specific cellular labelling but also for single particle tracking because of the improved optical performance. PMID- 25141183 TI - European Journal of Sport Science gears up its social media. PMID- 25141181 TI - Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis. AB - Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean. PMID- 25141185 TI - Novel repair of stapedial footplate defect associated with recurrent meningitis. AB - OBJECTIVE: Recurrent meningitis resulting from a partial defect of the stapedial footplate is most frequently treated by complete obliteration of the inner ear. Herein, we report the use of a partial obliteration technique in which the fistula is plugged with a shaped incus. PATIENTS: A 5-year-old girl and a 7-year old boy who had congenital inner ear malformations both developed recurrent meningitis. High-resolution computed tomography (HRCT) revealed soft tissue opacities between the mastoid air cells and the mesotympanum. Exploratory tympanotomies were performed, revealing cerebrospinal fluid (CSF) leakages from fistulae at the stapes footplate in both patients. INTERVENTIONS: In each case, the vestibule was partially obliterated with temporalis fascia and modified incus remnant. Bone dust and fibrin were also applied. MAIN OUTCOME MEASURES: Recurrence of CSF leakage and patient symptoms. RESULTS: None of the patients exhibited vertigo or dizziness after surgery, and meningitis did not recur during the follow-up period. CONCLUSIONS: Compete obliteration of the inner ear space can be avoided by using this technique, thereby leaving room for future cochlear implantation in addition to reducing direct injury to the vestibular system. PMID- 25141184 TI - Melanoma incidence and patient compliance in a targeted melanoma screening intervention. One-year follow-up in a large French cohort of high-risk patients. AB - BACKGROUND: Early diagnosis of melanoma can save lives. However, mass screening is not recommended, and few studies have addressed targeted screening. OBJECTIVE: To evaluate a targeted melanoma screening intervention by measuring the cumulative melanoma incidence and patient compliance with the screening. METHODS: This was a prospective one-year follow-up of a cohort of 3923 French patients at elevated risk of melanoma who were recruited from April to October 2011 by 78 GPs using the Self-assessment of melanoma risk score. Following standard practice, based on the GPs' opinions, a subset of these patients was referred to dermatologists. The dermatologists scheduled excisions when required. Melanomas were confirmed using pathology reports. Patient compliance with the clinical pathway was assessed retrospectively. The cohort was followed prospectively using three data sources (GPs, dermatologists and patients). Analyses of factors associated with compliance were performed using multiple logistic regression. RESULTS: GPs examined the skin of 3923 high-risk patients, 1506 of whom were referred to dermatologists. Nine cases of melanoma were diagnosed, corresponding to a cumulative incidence of 229.4/100,000. Of the referred patients, 57.9% attended the dermatologist consultation. Patient attendance was better when the GPs provided a dermatologist's name (OR = 2.15, 95% CI: 1.51-3.09). A delay before consulting a dermatologist was inversely associated with the estimated lesion malignancy. CONCLUSION: Performing this targeted screening in a high-risk population resulted in a high melanoma detection rate, despite moderate compliance. Observations suggest that naming a dermatologist is a simple, inexpensive means of increasing patient compliance with the screening. PMID- 25141186 TI - Acute facial paralysis and otomastoiditis as presenting symptoms of myeloid sarcoma. PMID- 25141187 TI - Report of endoscopic cochlear implantation. AB - OBJECTIVES: To report patient outcomes after transcanal endoscopic cochlear implantation for sensorineural hearing loss. PATIENTS: Males and female subjects more than 7 years old with sensorineural hearing loss (confirmed with audiologic studies) were selected. CT imaging was used to rule out any anatomic anomalies of the temporal bone. Smaller pediatric patients whose canal might still be growing and who might have a higher incidence of otitis media and otitis externa were excluded. Obese adults whose canal skin was too thick to allow good access down the ear canal were also excluded. INTERVENTION(S): Surgical (therapeutic). Endoscopic cochlear implantation using a transcanal approach. MAIN OUTCOME MEASURE(S): Implant position and function. Postoperative complications specifically related to transcanal approach and use of the endoscope. RESULTS: Twenty-five endoscopic cochlear implantations were performed in 24 ears on 11 female and 10 male subjects aged 7-65 years. Eight patients were implanted in Brazil, and 13 patients (17 yr) were implanted in the United States. All implants were fully inserted into the scala tympani, and 24 functioned normally with appropriate thresholds. Mean time of follow-up was 16 months (SD, +/-7.2). The chorda tympani was sacrificed in 2 of 25 procedures, 12 EAC/TM tears occurred which healed by the second follow-up visit. No injury to the facial nerve was observed. One postoperative wound infection and 1 otitis externa each resolved with 1 week of antibiotics. Implant array was visible through the EACs skin but not exposed in 6 of 24 ears. CONCLUSION: Endoscopic cochlear implantation may become a viable, safe, and feasible alternative to the standard open transmastoid approach. PMID- 25141188 TI - Association of smoking and snuffing with dental caries occurrence in a young male population in Finland: a cross-sectional study. AB - OBJECTIVE: The aim of this study was to investigate the prevalence of smoking and snuffing habits in association with dental caries occurrence in a male cohort born in the early 1990s in Finland. The impact of health behaviours and factors related to the place of residence were included in analyses. MATERIALS AND METHODS: Oral health of 8537 conscripts was screened in a cross-sectional study. In the same occasion they also answered a questionnaire covering their smoking and snuffing habits and other background factors. The residence-related factors were obtained from the Defence Forces' database. Cross-tabulation together with chi-squared test and generalized linear mixed models were used for analyses. RESULTS: Almost forty per cent (39.4%) of the men reported smoking daily and 9.0% reported daily snuffing. Restorative treatment need of those who reported frequent smoking was more than 2-fold (mean DT = 2.22) compared to the non smokers (mean DT = 1.07). Smoking was statistically significantly associated with other harmful health behaviours. The snuffers reported more snacking than the non smokers, but were most frequent brushers. The result from the statistical modelling showed that smoking, low tooth brushing frequency, eating sweets and consuming energy drinks frequently were significantly associated with restorative treatment need. CONCLUSION: In this cross-sectional study, association between smoking and dental caries was distinct. The high rate of restorative treatment need among smokers may be explained by their poor health behaviours. Dietary habits of the snuffers seem harmful too, but are compensated by good tooth brushing frequency. PMID- 25141189 TI - EGFR and EGFRvIII analysis in glioblastoma as therapeutic biomarkers. AB - Introduction. EGFR and EGFRvIII analysis is of current interest because of new EGFRvIII vaccine trials opened in the UK. EGFR activation promotes cellular proliferation via activation of MAPK and PI3K-Akt pathways. EGFRvIII is the most common variant resulting from an in-frame deletion of 801bp, leading to constitutively active EGFR. Method. 51 glioblastoma samples from a cohort of 50 patients were tested for EGFR amplification by FISH and immunohistochemistry and EGFRvIII expression by reverse-transcriptase PCR (RT-PCR), and immunohistochemistry. EGFR and EGFRvIII expression was compared with Overall Survival in the cohort. Results. Overall 22/51 samples (43%) were positive for EGFR, 16/51 (31%) were positive for EGFRvIII and 13/51 (25%) were positive for both. 9/51 cases (18%) were positive for EGFR alone, and 3/51 (6%) were positive for EGFRvIII alone. Of the EGFR positive cases, 22/51 (43%) were positive by FISH, 24/51 (47%) were positive by IHC and 2/51 (4%) were discrepant between methods (positive by IHC but non-amplified by FISH). Of the EGFRvIII positive cases, 16/51 (31%) were positive by RT-PCR, 17/51 (33%) were positive by IHC and 1/51 (2%) sample was discrepant (positive by IHC but not by RT-PCR). Neither EGFRvIII or EGFR are predictive of overall survival in this cohort. Conclusion. In our cohort, 25/51 (49%) of GBM showed EGFR alterations, including 16/51 (31%) with EGFRvIII. There was high concordance between IHC and FISH (96%) and IHC and RT-PCR (98%) as diagnostic methods. Neither EGFR or EGFRvIII is predictive of overall survival in this cohort. These results are key for selecting patients for novel individualised anti-EGFR therapies. PMID- 25141190 TI - Nutrient-specific compensatory feeding in a mammalian carnivore, the mink, Neovison vison. AB - Balancing of macronutrient intake has only recently been demonstrated in predators. In particular, the ability to regulate carbohydrate intake is little studied in obligate carnivores, as carbohydrate is present at very low concentrations in prey animal tissue. In the present study, we determined whether American mink (Neovison vison) would compensate for dietary nutritional imbalances by foraging for complementary macronutrients (protein, lipid and carbohydrate) when subsequently given a dietary choice. We used three food pairings, within which two macronutrients differed relative to each other (high v. low concentration), while the third was kept at a constant level. The mink were first restricted to a single nutritionally imbalanced food for 7 d and then given a free choice to feed from the same food or a nutritionally complementary food for three consecutive days. When restricted to nutritionally imbalanced foods, the mink were willing to overingest protein only to a certain level ('ceiling'). When subsequently given a choice, the mink compensated for the period of nutritional imbalance by selecting the nutritionally complementary food in the food choice pairing. Notably, this rebalancing occurred for all the three macronutrients, including carbohydrate, which is particularly interesting as carbohydrate is not a major macronutrient for obligate carnivores in nature. However, there was also a ceiling to carbohydrate intake, as has been demonstrated previously in domestic cats. The results of the present study show that mink regulate their intake of all the three macronutrients within limits imposed by ceilings on protein and carbohydrate intake and that they will compensate for a period of nutritional imbalance by subsequently selecting nutritionally complementary foods. PMID- 25141191 TI - Alignment between chronic disease policy and practice: case study at a primary care facility. AB - BACKGROUND: Chronic disease is by far the leading cause of death worldwide and of increasing concern in low- and middle-income countries, including South Africa, where chronic diseases disproportionately affect the poor living in urban settings. The Provincial Government of the Western Cape (PGWC) has prioritized the management of chronic diseases and has developed a policy and framework (Adult Chronic Disease Management Policy 2009) to guide and improve the prevention and management of chronic diseases at a primary care level. The aim of this study is to assess the alignment of current primary care practices with the PGWC Adult Chronic Disease Management policy. METHODS: One comprehensive primary care facility in a Cape Town health district was used as a case study. Data was collected via semi-structured interviews (n = 10), focus groups (n = 8) and document review. Participants in this study included clinical staff involved in chronic disease management at the facility and at a provincial level. Data previously collected using the Integrated Audit Tool for Chronic Disease Management (part of the PGWC Adult Chronic Disease Management policy) formed the basis of the guide questions used in focus groups and interviews. RESULTS: The results of this research indicate a significant gap between policy and its implementation to improve and support chronic disease management at this primary care facility. A major factor seems to be poor policy knowledge by clinicians, which contributes to an individual rather than a team approach in the management of chronic disease patients. Poor interaction between facility- and community based services also emerged. A number of factors were identified that seemed to contribute to poor policy implementation, the majority of which were staff related and ultimately resulted in a decrease in the quality of patient care. CONCLUSIONS: Chronic disease policy implementation needs to be improved in order to support chronic disease management at this facility. It is possible that similar findings and factors are present at other primary care facilities in Cape Town. At a philosophical level, this research highlights the tension between primary health care principles and a diseased-based approach in a primary care setting. PMID- 25141192 TI - Species-specific detection and identification of fusarium species complex, the causal agent of sugarcane pokkah boeng in China. AB - BACKGROUND: Pokkah boeng disease caused by the Fusarium species complex results in significant yield losses in sugarcane. Thus, the rapid and accurate detection and identification of the pathogen is urgently required to manage and prevent the spreading of sugarcane pokkah boeng. METHODS: A total of 101 isolates were recovered from the pokkah boeng samples collected from five major sugarcane production areas in China throughout 2012 and 2013. The causal pathogen was identified by morphological observation, pathogenicity test, and phylogenetic analysis based on the fungus-conserved rDNA-ITS. Species-specific TaqMan real time PCR and conventional PCR methods were developed for rapid and accurate detection of the causal agent of sugarcane pokkah boeng. The specificity and sensitivity of PCR assay were also evaluated on a total of 84 isolates of Fusarium from China and several isolates from other fungal pathogens of Sporisorium scitamineum and Phoma sp. and sugarcane endophyte of Acremonium sp. RESULT: Two Fusarium species (F. verticillioides and F. proliferatum) that caused sugarcane pokahh boeng were identified by morphological observation, pathogenicity test, and phylogenetic analysis. Species-specific TaqMan PCR and conventional PCR were designed and optimized to target their rDNA-ITS regions. The sensitivity of the TaqMan PCR was approximately 10 pg of fungal DNA input, which was 1,000-fold over conventional PCR, and successfully detected pokkah boeng in the field-grown sugarcane. CONCLUSIONS/SIGNIFICANCE: This study was the first to identify two species, F. verticillioides and F. proliferatum, that were causal pathogens of sugarcane pokkah boeng in China. It also described the development of a species-specific PCR assay to detect and confirm these pathogens in sugarcane plants from mainland China. This method will be very useful for a broad range of research endeavors as well as the regulatory response and management of sugarcane pokkah boeng. PMID- 25141193 TI - Tracking from the tropics reveals behaviour of juvenile songbirds on their first spring migration. AB - Juvenile songbirds on spring migration travel from tropical wintering sites to temperate breeding destinations thousands of kilometres away with no prior experience to guide them. We provide a first glimpse at the migration timing, routes, and stopover behaviour of juvenile wood thrushes (Hylocichla mustelina) on their inaugural spring migration by using miniaturized archival geolocators to track them from Central America to the U.S. and Canada. We found significant differences between the timing of juvenile migration and that of more experienced adults: juveniles not only departed later from tropical wintering sites relative to adults, they also became progressively later as they moved northward. The increasing delay was driven by more frequent short stops by juveniles along their migration route, particularly in the U.S. as they got closer to breeding sites. Surprisingly, juveniles were just as likely as adults to cross the Gulf of Mexico, an open-water crossing of 800-1000 km, and migration route at the Gulf was not significantly different for juveniles relative to adults. To determine if the later departure of juveniles was related to poor body condition in winter relative to adults, we examined percent lean body mass, fat scores, and pectoral muscle scores of juvenile versus adult birds at a wintering site in Belize. We found no age-related differences in body condition. Later migration timing of juveniles relative to adults could be an adaptive strategy (as opposed to condition-dependent) to avoid the high costs of fast migration and competition for breeding territories with experienced and larger adults. We did find significant differences in wing size between adults and juveniles, which could contribute to lower flight efficiency of juveniles and thus slower overall migration speed. We provide the first step toward understanding the "black box" of juvenile songbird migration by documenting their migration timing and en route performance. PMID- 25141194 TI - Microbes and cancer geography: can we exploit recent lessons from the gut system to oral cancer context? PMID- 25141196 TI - Oral cavity infection: an adverse effect after the treatment of oral cancer in aged individuals. AB - OBJECTIVE: The immune compromised patients after treatment of oral cancer may have a chance of infection by drug-resistant opportunistic microbes. We investigated the occurrence of opportunistic microorganisms in aged individuals receiving follow-up examinations after treatment of oral cancer in China. MATERIAL AND METHODS: These patients were used as test group and the respective age grouped healthy individuals as control group. In this study, the oral cavity microorganisms such as bacteria and yeast were taken for the analysis. After the screening of representative microorganisms, their aptitude of pervasiveness against drugs was studied. Here, we used antimicrobial agents which are common in clinical practice. We also performed studies to investigate the presence of toxin genes in methicillin-resistant S. aureus (MRSA). RESULTS: The results indicate that the prevalence of drug-resistant microbes was more pronounced in oral cancer patients after initial treatment above 70 years old. The oxacillin resistance of S. aureus isolate confirms that the prevalence of MRSA is increasing in accordance to age-factor and immune compromise in elderly patients. CONCLUSIONS: This study reveals the occurrence of drug-resistant opportunistic microorganisms in oral cavity after treatment for oral cancer in aged individuals. Special attention should be directed to MRSA during the treatment of oral cancer, and to realize the fact of immune compromise in elderly patients. PMID- 25141195 TI - A framework for understanding shared substrates of airway protection. AB - Deficits of airway protection can have deleterious effects to health and quality of life. Effective airway protection requires a continuum of behaviors including swallowing and cough. Swallowing prevents material from entering the airway and coughing ejects endogenous material from the airway. There is significant overlap between the control mechanisms for swallowing and cough. In this review we will present the existing literature to support a novel framework for understanding shared substrates of airway protection. This framework was originally adapted from Eccles' model of cough (2009) by Hegland, et al. (2012). It will serve to provide a basis from which to develop future studies and test specific hypotheses that advance our field and ultimately improve outcomes for people with airway protective deficits. PMID- 25141197 TI - Influence of bismuth oxide concentration on the pH level and biocompatibility of white Portland cement. AB - OBJECTIVES: To investigate if there is a relation between the increase of bismuth oxide and the decrease of pH levels and an intensification of toxicity in the Portland cement. MATERIAL AND METHODS: White Portland cement (WPC) was mixed with 0, 15, 20, 30 and 50% bismuth oxide, in weight. For the pH level test, polyethylene tubes were filled with the cements and immersed in Milli-Q water for 15, 30 and 60 days. After each period, the increase of the pH level was assessed. For the biocompatibility, two polyethylene tubes filled with the cements were implanted in ninety albino rats (n=6). The analysis of the intensity of the inflammatory infiltrate was performed after 15, 30 and 60 days. The statistical analysis was performed using the Kruskal-Wallis, Dunn and Friedman tests for the pH level and the Kruskal-Wallis and Dunn tests for the biological analysis (p<0.05). RESULTS: The results showed an increase of the pH level after 15 days, followed by a slight increase after 30 days and a decrease after 60 days. There were no significant statistical differences among the groups (p>0.05). For the inflammatory infiltrates, no significant statistical differences were found among the groups in each period (p>0.05). The 15% WPC showed a significant decrease of the inflammatory infiltrate from 15 to 30 and 60 days (p<0.05). CONCLUSIONS: The addition of bismuth oxide into Portland cement did not affect the pH level and the biological response. The concentration of 15% of bismuth oxide resulted in significant reduction in inflammatory response in comparison with the other concentrations evaluated. PMID- 25141198 TI - An in vitro assessment of type, position and incidence of isthmus in human permanent molars. AB - Root canal anatomical complexities, such as isthmus, may limit the action of the endodontic instruments, irrigant solutions and intracanal medications, leading to endodontic treatment failure. OBJECTIVES: This in vitro study assessed the type, position and incidence of isthmus in human permanent molars. MATERIAL AND METHODS: One hundred and twenty eight upper and lower first and second permanent molars were analyzed. The roots were embedded in transparent resin, and then split at different distances from the apex (1.0-2.5-4.0-5.5-7.0 mm). Following the sample examination in stereomicroscope, the data were submitted to chi-square statistical test at a 5% significance level. RESULTS: The highest isthmus incidence was at 7.0 mm from the root apex in all samples, except the distal root of lower molars (at 5.5 mm). In upper and lower molars, type V (complete isthmus with a continuous opening between the two main root canals) was the most common classification of isthmus (28.8%). In the mesial root of first and second mandibular molars, type IV had the highest incidence (36% and 23.9%, respectively). CONCLUSION: It was concluded that isthmus was widely found in flat roots, with a low percentage in areas close to the apex. In upper and lower molars, these structures were most frequently found at 7 mm from the apex. PMID- 25141199 TI - Apoptosis of human tongue squamous cell carcinoma cell (CAL-27) induced by Lactobacillus sp. A-2 metabolites. AB - OBJECTIVE: To study the effect of Lactobacillus sp. A-2 metabolites on viability of CAL-27 cells and apoptosis in CAL-27 cells. METHODS: Lactobacillus sp. A-2 metabolites 1 and 2 (LM1 and LM2) were obtained by culturing Lactobacillus sp. A 2 in reconstituted whey medium and whey-inulin medium; the cultured CAL-27 cells were treated with different concentrations of LM1 and LM2 (0, 3, 6, 12, 24, 48 mg/mL) and assayed by methyl thiazolyltetrazolium (MTT) method; morphological changes of apoptotic cell were observed under fluorescence microscopy by acridine orange (Ao) fluorescent staining; flow cytometry method (FCM) and agarose gel electrophoresis were used to detect the apoptosis of CAL-27 cells treated LM1 and LM2. RESULTS: The different concentrations of LM1 and LM2 could restrain the growth of CAL-27 cells, and in a dose-dependent manner; the apoptosis of CAL-27 cells was obviously induced and was time-dependent. CONCLUSIONS: Viability of CAL 27 cells was inhibited by Lactobacillus sp. A-2 metabolites; Lactobacillus sp. A 2 metabolites could induce CAL-27 cells apoptosis; study on the bioactive compounds in the Lactobacillus sp. A-2 metabolites and their molecular mechanism is in progress. PMID- 25141200 TI - Effects of coronal substrates and water storage on the microhardness of a resin cement used for luting ceramic crowns. AB - Composite resin and metallic posts are the materials most employed for reconstruction of teeth presenting partial or total destruction of crowns. Resin based cements have been widely used for cementation of ceramic crowns. The success of cementation depends on the achievement of adequate cement curing. OBJECTIVES: To evaluate the microhardness of Variolink(r) II (Ivoclar Vivadent, Schaan, Liechtenstein), used for cementing ceramic crowns onto three different coronal substrate preparations (dentin, metal, and composite resin), after 7 days and 3 months of water storage. The evaluation was performed along the cement line in the cervical, medium and occlusal thirds on the buccal and lingual aspects, and on the occlusal surface. MATERIAL AND METHODS: Thirty molars were distributed in three groups (N=10) according to the type of coronal substrate: Group D- the prepared surfaces were kept in dentin; Groups M (metal) and R (resin)- the crowns were sectioned at the level of the cementoenamel junction and restored with metallic cast posts or resin build-up cores, respectively. The crowns were fabricated in ceramic IPS e.max(r) Press (Ivoclar Vivadent, Schaan, Liechtenstein) and luted with Variolink II. After 7 days of water storage, 5 specimens of each group were sectioned in buccolingual direction for microhardness measurements. The other specimens (N=5) were kept stored in deionized water at 37oC for three months, followed by sectioning and microhardness measurements. RESULTS: Data were first analyzed by three-way ANOVA that did not reveal significant differences between thirds and occlusal surface (p=0.231). Two-way ANOVA showed significant effect of substrates (p<0.001) and the Tukey test revealed that microhardness was significantly lower when crowns were cemented on resin cores and tested after 7 days of water storage (p=0.007). CONCLUSION: The type of material employed for coronal reconstruction of preparations for prosthetic purposes may influence the cement properties. PMID- 25141201 TI - Effects of solvent evaporation on water sorption/solubility and nanoleakage of adhesive systems. AB - OBJECTIVE: To evaluate the influence of solvent evaporation in the kinetics of water diffusion (water sorption-WS, solubility-SL, and net water uptake) and nanoleakage of adhesive systems. MATERIAL AND METHODS: Disk-shaped specimens (5.0 mm in diameter x 0.8 mm in thickness) were produced (N=48) using the adhesives: Clearfil S3 Bond (CS3)/Kuraray, Clearfil SE Bond - control group (CSE)/Kuraray, Optibond Solo Plus (OS)/Kerr and Scotchbond Universal Adhesive (SBU)/3M ESPE. The solvents were either evaporated for 30 s or not evaporated (N=24/per group), and then photoactivated for 80 s (550 mW/cm2). After desiccation, the specimens were weighed and stored in distilled water (N=12) or mineral oil (N=12) to evaluate the water diffusion over a 7-day period. Net water uptake (%) was also calculated as the sum of WS and SL. Data were submitted to 3-way ANOVA/Tukey's test (alpha=5%). The nanoleakage expression in three additional specimens per group was also evaluated after ammoniacal silver impregnation after 7 days of water storage under SEM. RESULTS: Statistical analysis revealed that only the factor "adhesive" was significant (p<0.05). Solvent evaporation had no influence in the WS and SL of the adhesives. CSE (control) presented significantly lower net uptake (5.4%). The nanoleakage was enhanced by the presence of solvent in the adhesives. CONCLUSIONS: Although the evaporation has no effect in the kinetics of water diffusion, the nanoleakage expression of the adhesives tested increases when the solvents are not evaporated. PMID- 25141202 TI - Evaluation of shear bond strength of two resin-based composites and glass ionomer cement to pure tricalcium silicate-based cement (Biodentine(r)). AB - OBJECTIVES: Tricalcium silicate is the major constituent phase in mineral trioxide aggregate (MTA). It is thus postulated that pure tricalcium silicate can replace the Portland cement component of MTA. The aim of this study was to evaluate bond strength of methacrylate-based (MB) composites, silorane-based (SB) composites, and glass ionomer cement (GIC) to Biodentine(r) and mineral trioxide aggregate (MTA). MATERIAL AND METHODS: Acrylic blocks (n=90, 2 mm high, 5 mm diameter central hole) were prepared. In 45 of the samples, the holes were fully filled with Biodentine(r) and in the other 45 samples, the holes were fully filled with MTA. The Biodentine(r) and the MTA samples were randomly divided into 3 subgroups of 15 specimens each: Group-1: MB composite; Group-2: SB composite; and Group-3: GIC. For the shear bond strength (SBS) test, each block was secured in a universal testing machine. RESULTS: The highest (17.7 +/- 6.2 MPa) and the lowest (5.8 +/- 3.2 MPa) bond strength values were recorded for the MB composite Biodentine(r) and the GIC-MTA, respectively. Although the MB composite showed significantly higher bond strength to Biodentine (17.7 +/- 6.2) than it did to MTA (8.9 +/- 5.7) (p < 0.001), the SB composite (SB and MTA = 7.4 +/- 3.3; SB and Biodentine(r) = 8.0 +/- 3,6) and GIC (GIC and MTA = 5.8 +/- 3.2; GIC and Biodentine = 6.7 +/- 2.6) showed similar bond strength performance with MTA compared with Biodentine (p = 0.73 and p = 0.38, respectively). CONCLUSIONS: The new pure tricalcium-based pulp capping, repair, and endodontic material showed higher shear bond scores compared to MTA when used with the MB composite. PMID- 25141203 TI - Randomized controlled clinical trial of long-term chemo-mechanical caries removal using PapacarieTM gel. AB - OBJECTIVES: Compare the effectiveness of PapacarieTM gel for the chemo-mechanical removal of carious lesions on primary teeth to conventional caries removal with a low-speed bur with regard to execution time, clinical aspects and radiographic findings. MATERIAL AND METHODS: A randomized controlled clinical trial with a split-mouth design was carried out. The sample was composed of 20 children aged four to seven years, in whom 40 deciduous teeth were randomly divided into two groups: chemo-mechanical caries removal with PapacarieTM and removal of carious dentin with a low-speed bur. Each child underwent both procedures and served as his/her own control. Restorations were performed with glass ionomer cement. The time required to perform the procedure was also analyzed. The patients underwent longitudinal clinical and radiographic follow-up of the restorations. RESULTS: No statistically significant difference between groups was found regarding the time required to perform the procedures and the radiographic follow up. Statistically significant differences between groups were found in the clinical evaluation at 6 and 18 months after treatment. CONCLUSION: PapacarieTM is as effective as the traditional method for the removal of carious dentin on deciduous teeth, but offers the advantages of the preservation of sound dental tissue as well as the avoidance of sharp rotary instruments and local anesthesia. PMID- 25141204 TI - Temporomandibular disorders among Brazilian adolescents: reliability and validity of a screening questionnaire. AB - Temporomandibular disorders (TMD) screeners assume significant item overlap with the screening questionnaire proposed by the American Academy of Orofacial Pain (AAOP). OBJECTIVE: To test the reliability and validity of the Portuguese version of AAOP questions for TMD screening among adolescents. MATERIAL AND METHODS: Diagnoses from Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I were used as reference standard. Reliability was evaluated by internal consistency (KR-20) and inter-item correlation. Validity was tested by sensitivity, specificity, predictive values, accuracy and receiver operating characteristic (ROC) curves, the relationship between the true-positive rate (sensitivity) and the false-positive rate (specificity). Test-retest reliability of AAOP questions and intra-examiner reproducibility of RDC/TMD Axis I were tested with kappa statistics. RESULTS: The sample consisted of 1307 Brazilian adolescents (56.8% girls; n=742), with mean age of 12.72 years (12.69 F/12.75 M). According to RDC/TMD, 397 [30.4% (32.7% F/27.3% M)] of adolescents presented TMD, of which 330 [25.2% (27.6% F/22.2% M)] were painful TMD. Because of low consistency, items #8 and #10 of the AAOP questionnaire were excluded. Remaining items (of the long questionnaire version) showed good consistency and validity for three positive responses or more. After logistic regression, items #4, #6, #7 and #9 also showed satisfactory consistency and validity for two or more positive responses (short questionnaire version). Both versions demonstrated excellent specificity (about 90%), but higher sensitivity for detecting painful TMD (78.2%). Better reproducibility was obtained for the short version (k=0.840). CONCLUSIONS: The Portuguese version of AAOP questions showed both good reliability and validity for the screening of TMD among adolescents, especially painful TMD, according to RDC/TMD. PMID- 25141205 TI - Velar activity in individuals with velopharyngeal insufficiency assessed by acoustic rhinometry. AB - Acoustic rhinometry is routinely used for the evaluation of nasal patency. OBJECTIVE: To investigate whether the technique is able to identify the impairment of velopharyngeal (VP) activity in individuals with clinical diagnosis of velopharyngeal insufficiency (VPI). METHODS: Twenty subjects with repaired cleft palate and inadequate velopharyngeal function (IVF) and 18 non-cleft controls with adequate velopharyngeal function (AVF), adults, of both genders, were evaluated. Area-distance curves were obtained during VP rest and speech activity, using an Eccovision Acoustic Rhinometry system. Volume was determined by integrating the area under the curve at the segment corresponding to the nasopharynx. VP activity (DeltaV) was estimated by the absolute and relative differences between nasopharyngeal volume at rest (Vr) and during an unreleased/k/ production (Vk). The efficiency of the technique to discriminate IVF and AVF was assessed by a ROC curve. RESULTS: Mean Vk and Vr values (+/- SD) obtained were: 23.2 +/- 3.6 cm3 and 15.9 +/- 3.8 cm3 (AVF group), and 22.7 +/- 7.9 cm3 and 20.7 +/- 7.4 cm3 (IVF group), corresponding to a mean DeltaV decay of 7.3 cm3 (31%) for the AVF group and a significantly smaller DeltaV decay of 2.0 cm3 (9%) for the IVF group (p < 0.05). Seventy percent of the IVF individuals showed a DeltaV suggesting impaired VP function (below the cutoff score of 3.0 cm3 which maximized both sensitivity and specificity of the test), confirming clinical diagnosis. CONCLUSION: Acoustic rhinometry was able to identify, with a good discriminatory power, the impairment of VP activity which characterizes VPI. PMID- 25141206 TI - The use of a DNA stabilizer in human dental tissues stored under different temperature conditions and time intervals. AB - OBJECTIVE: The present study evaluated the use of a reagent to stabilize the DNA extracted from human dental tissues stored under different temperature conditions and time intervals. MATERIAL AND METHODS: A total of 161 teeth were divided into two distinct groups: intact teeth and isolated dental pulp tissue. The samples were stored with or without the product at different time intervals and temperature. After storage, DNA extraction and genomic DNA quantification were performed using real-time PCR; the fragments of the 32 samples that represented each possible condition were analyzed to find the four pre-selected markers in STR analysis. RESULTS: The results of the quantification showed values ranging from 0.01 to 10,246.88 ng/MUL of DNA. The statistical difference in the quantity of DNA was observed when the factors related to the time and temperature of storage were analyzed. In relation to the use of the specific reagent, its use was relevant in the group of intact teeth when they were at room temperature for 30 and 180 days. The analysis of the fragments in the 32 selected samples was possible irrespective of the amount of DNA, confirming that the STR analysis using an automated method yields good results. CONCLUSIONS: The use of a specific reagent showed a significant difference in stabilizing DNA in samples of intact human teeth stored at room temperature for 30 and 180 days, while the results showed no justification for using the product under the other conditions tested. PMID- 25141208 TI - Microabrasion in tooth enamel discoloration defects: three cases with long-term follow-ups. AB - Superficial irregularities and certain intrinsic stains on the dental enamel surfaces can be resolved by enamel microabrasion, however, treatment for such defects need to be confined to the outermost regions of the enamel surface. Dental bleaching and resin-based composite repair are also often useful for certain situations for tooth color corrections. This article presented and discussed the indications and limitations of enamel microabrasion treatment. Three case reports treated by enamel microabrasion were also presented after 11, 20 and 23 years of follow-ups. PMID- 25141207 TI - Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status. AB - Previous studies demonstrate that the balance between pro- and anti-inflammatory mediators determines the stable or progressive nature of periapical granulomas by modulating the balance of the osteoclastogenic factor RANKL and its antagonist OPG. However, the cytokine networks operating in the development of periapical lesions are quite more complex than what the simple pro- versus anti-inflammatory mediators' paradigm suggests. Here we simultaneously investigated the patterns of Th1, Th2, Th9, Th17, Th22, Thf, Tr1 and Tregs cytokines/markers expression in human periapical granulomas. METHODS: The expression of TNF-alpha, IFN-gamma, IL 17A, IL23, IL21, IL-33, IL-10, IL-4, IL-9, IL-22, FOXp3 markers (via RealTimePCR array) was accessed in active/progressive (N=40) versus inactive/stable (N=70) periapical granulomas (as determined by RANKL/OPG expression ratio), and also to compare these samples with a panel of control specimens (N=26). A cluster analysis of 13 cytokine levels was performed to examine possible clustering between the cytokines in a total of 110 granulomas. RESULTS: The expression of all target cytokines was higher in the granulomas than in control samples. TNF alpha, IFN-gamma, IL-17A and IL-21 mRNA levels were significantly higher in active granulomas, while in inactive lesions the expression levels of IL-4, IL-9, IL-10, IL-22 and FOXp3 were higher than in active granulomas. Five clusters were identified in inactive lesion groups, being the variance in the expression levels of IL-17, IL-10, FOXp3, IFN-gamma, IL-9, IL-33 and IL-4 statistically significant (KW p<0.05). Three clusters were identified in active lesions, being the variance in the expression levels of IL-22, IL-10, IFN-gamma, IL-17, IL-33, FOXp3, IL-21 and RANKL statistically significant (KW p<0.05). CONCLUSION: There is a clear dichotomy in the profile of cytokine expression in inactive and active periapical lesions. While the widespread cytokine expression seems to be a feature of chronic lesions, hierarchical cluster analysis demonstrates the association of TNF-alpha, IL-21, IL-17 and IFN-gamma with lesions activity, and the association of FOXP3, IL-10, IL-9, IL-4 and IL-22 with lesions inactivity. PMID- 25141209 TI - Work-related exacerbation of asthma among adults treated by pulmonary specialists. AB - The most common chronic occupational lung disease is occupational asthma. This study aimed to assess the prevalence of work-related respiratory symptoms (WRS) in asthmatic adults at pulmonary clinics. A cross-sectional study was performed. Current employed subjects were subdivided into 2 groups by WRS status according to questionnaire mainly based on one developed by the National Institute for Occupational Safety and Health (NIOSH). Subjects' occupation and workplace exposures were evaluated by asthma-specific job exposure matrix (JEM). Thirty nine of 179 current employed asthmatics had WRS. Subjects with WRS were more likely to have self-reported allergy and exposure to low-molecular-weight antigens (prevalence ratio [PR]: 2.7). The 2 most frequent occupational classes for asthmatics with WRS were trades, transport and equipment operators, and processing and manufacturing. Self-reported allergy, high-risk exposures, and occupations unique to processing, manufacturing, and utilities were estimated to be risk factors of WRS. PMID- 25141210 TI - Levels of central oxytocin and glucocorticoid receptor and serum adrenocorticotropic hormone and corticosterone in mandarin voles with different levels of sociability. AB - Sociability is the prerequisite to social living. Oxytocin and the hypothalamo pituitary-adrenocortical axis mediate various social behaviors across different social contexts in different rodents. We hypothesized that they also mediate levels of non-reproductive social behavior. Here we explored naturally occurring variation in sociability through a social preference test and compared central oxytocin, glucocorticoid receptors, serum adrenocorticotropic hormone and corticosterone in mandarin voles with different levels of sociability. We found that low-social voles showed higher levels of anxiety-like behavior in open field tests, and had more serum adrenocorticotropic hormone and corticosterone than high-social voles. High-social individuals had more glucocorticoid receptor positive neurons in the hippocampus and more oxytocin positive neurons in the paraventricular nuclei and supraoptic nuclei of the hypothalamus than low-social individuals. Within the same level of sociability, females had more oxytocin positive neurons in the paraventricular nuclei and supraoptic nuclei of the hypothalamus than males. These results indicate that naturally occurring social preferences are associated with higher levels of central oxytocin and hippocampus glucocorticoid receptor and lower levels of anxiety and serum adrenocorticotropic hormone and corticosterone. PMID- 25141212 TI - Strong discrepancies between local temperature mapping and interpolated climatic grids in tropical mountainous agricultural landscapes. AB - Bridging the gap between the predictions of coarse-scale climate models and the fine-scale climatic reality of species is a key issue of climate change biology research. While it is now well known that most organisms do not experience the climatic conditions recorded at weather stations, there is little information on the discrepancies between microclimates and global interpolated temperatures used in species distribution models, and their consequences for organisms' performance. To address this issue, we examined the fine-scale spatiotemporal heterogeneity in air, crop canopy and soil temperatures of agricultural landscapes in the Ecuadorian Andes and compared them to predictions of global interpolated climatic grids. Temperature time-series were measured in air, canopy and soil for 108 localities at three altitudes and analysed using Fourier transform. Discrepancies between local temperatures vs. global interpolated grids and their implications for pest performance were then mapped and analysed using GIS statistical toolbox. Our results showed that global interpolated predictions over-estimate by 77.5 +/- 10% and under-estimate by 82.1 +/- 12% local minimum and maximum air temperatures recorded in the studied grid. Additional modifications of local air temperatures were due to the thermal buffering of plant canopies (from -2.7 degrees K during daytime to 1.3 degrees K during night-time) and soils (from -4.9 degrees K during daytime to 6.7 degrees K during night-time) with a significant effect of crop phenology on the buffer effect. This discrepancies between interpolated and local temperatures strongly affected predictions of the performance of an ectothermic crop pest as interpolated temperatures predicted pest growth rates 2.3-4.3 times lower than those predicted by local temperatures. This study provides quantitative information on the limitation of coarse-scale climate data to capture the reality of the climatic environment experienced by living organisms. In highly heterogeneous region such as tropical mountains, caution should therefore be taken when using global models to infer local-scale biological processes. PMID- 25141211 TI - Trafficking of kainate receptors. AB - Ionotropic glutamate receptors (iGluRs) mediate the vast majority of excitatory neurotransmission in the central nervous system of vertebrates. In the protein family of iGluRs, kainate receptors (KARs) comprise the probably least well understood receptor class. Although KARs act as key players in the regulation of synaptic network activity, many properties and functions of these proteins remain elusive until now. Especially the precise pre-, extra-, and postsynaptic localization of KARs plays a critical role for neuronal function, as an unbalanced localization of KARs would ultimately lead to dysregulated neuronal excitability. Recently, important advances in the understanding of the regulation of surface expression, function, and agonist-dependent endocytosis of KARs have been achieved. Post-translational modifications like PKC-mediated phosphorylation and SUMOylation have been reported to critically influence surface expression and endocytosis, while newly discovered auxiliary proteins were shown to shape the functional properties of KARs. PMID- 25141213 TI - Lead-induced impairments in the neural processes related to working memory function. AB - BACKGROUND: It is well known that lead exposure induces neurotoxic effects, which can result in a variety of neurocognitive dysfunction. Especially, occupational lead exposures in adults are associated with decreases in cognitive performance including working memory. Despite recent advances in human neuroimaging techniques, the neural correlates of lead-exposed cognitive impairment remain unclear. Therefore, this study was aimed to compare the neural activations in relation to working memory function between the lead-exposed subjects and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-one lead-exposed subjects and 34 healthy subjects performed an n-back memory task during MRI scan. We performed fMRI using the 1-back and 2-back memory tasks differing in cognitive demand. Functional MRI data were analyzed using within- and between-group analysis. We found that the lead-exposed subjects showed poorer working memory performance during high memory loading task than the healthy subjects. In addition, between group analyses revealed that the lead-exposed subjects showed reduced activation in the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, pre supplementary motor areas, and inferior parietal cortex. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that functional abnormalities in the frontoparietal working memory network might contribute to impairments in maintenance and manipulation of working memory in the lead-exposed subjects. PMID- 25141215 TI - Promising two-photon probes for in vivo detection of beta amyloid deposits. AB - Based on electronic structure calculations we propose that particular small-sized organic molecules - donor-acceptor substituted phenyl polymethines - can be used as two-photon diagnostic probes for non-invasive imaging of amyloid oligomers and fibrils, which are often referred to as the "early signatures" of Alzheimer's disease. PMID- 25141216 TI - Rhodium(III)-catalyzed C-C bond formation of quinoline N-oxides at the C-8 position under mild conditions. AB - The Rh(III)-catalyzed C-8 selective direct alkylation and alkynylation of quinoline N-oxides has been developed. The reactions proceeded highly efficiently at room temperature over a broad range of substrates with excellent regioselectivity and functional group tolerance. This development demonstrates the synthetic utility of the N-oxide directing group as a stepping stone for remote C-H functionalization of quinolines. PMID- 25141217 TI - On calculation of the electrostatic potential of a phosphatidylinositol phosphate containing phosphatidylcholine lipid membrane accounting for membrane dynamics. AB - Many signaling events require the binding of cytoplasmic proteins to cell membranes by recognition of specific charged lipids, such as phosphoinositol phosphates. As a model for a protein-membrane binding site, we consider one charged phosphoinositol phosphate (PtdIns(3)P) embedded in a phosphatidylcholine bilayer. As the protein-membrane binding is driven by electrostatic interactions, continuum solvent models require an accurate representation of the electrostatic potential of the phosphoinositol phosphate-containing membrane. We computed and analyzed the electrostatic potentials of snapshots taken at regular intervals from molecular dynamics simulations of the bilayer. We observe considerable variation in the electrostatic potential of the bilayer both along a single simulation and between simulations performed with the GAFF or CHARMM c36 force fields. However, we find that the choice of GAFF or CHARMM c36 parameters has little effect on the electrostatic potential of a given configuration of the bilayer with a PtdIns(3)P embedded in it. From our results, we propose a remedian averaging method for calculating the electrostatic potential of a membrane system that is suitable for simulations of protein-membrane binding with a continuum solvent model. PMID- 25141218 TI - Effect of diode laser in the treatment of patients with nonspecific chronic low back pain: a randomized controlled trial. AB - BACKGROUND DATA: Low back pain is a common, highly debilitating condition, whose severity is variable. This study evaluated the efficacy of treatment with Ga-Al As diode laser (980 nm) with a large diameter spot (32 cm(2)), in association with exercise therapy, in reducing pain. OBJECTIVE: The present study aimed to evaluate the pain reduction efficacy of treatment with the Ga-Al-As diode laser (980 nm) in combination with exercise therapy, in patients with chronic low back pain (CLBP). METHODS: This study evaluated 100 patients with CLBP (mean age 60 years) who were randomly assigned to two groups. The laser plus exercises group (Laser+EX: 50 patients) received low-level laser therapy (LLLT) with a diode laser, 980 nm, with a specific handpiece [32 cm(2) irradiation spot size, power 20 W in continuous wave (CW), fluence 37.5J/cm(2), total energy per point 1200 J] thrice weekly, and followed a daily exercise schedule for 3 weeks (5 days/week). The exercises group (EX: 50 patients) received placebo laser therapy plus daily exercises. The outcome was evaluated on the visual analogue pain scale (VAS), before and after treatment. RESULTS: At the end of the 3 week period, the Laser+EX group showed a significantly greater decrease in pain than did the EX group. There was a significant difference between the two groups, with average Delta VAS scores of 3.96 (Laser+EX group) and 2.23 (EX group). The Student's t test demonstrated a statistically significant difference between the two groups, at p<0.001. CONCLUSIONS: This study demonstrated that the use of diode laser (980 nm) with large diameter spot size, in association with exercise therapy, appears to be effective. Such treatment might be considered a valid therapeutic option within rehabilitation programs for nonspecific CLBP. PMID- 25141219 TI - Importance of excitation and trapping conditions in photosynthetic environment assisted energy transport. AB - It has been argued that excitonic energy transport in photosynthetic complexes is efficient because of a balance between coherent evolution and decoherence, a phenomenon called environment-assisted quantum transport (ENAQT). Studies of ENAQT have usually assumed that the excitation is initially localized on a particular chromophore, and that it is transferred to a reaction center through a similarly localized trap. However, these assumptions are not physically accurate. We show that more realistic models of excitation and trapping can lead to very different predictions about the importance of ENAQT. In particular, although ENAQT is a robust effect if one assumes a localized trap, its effect can be negligible if the trapping is more accurately modeled as Forster transfer to a reaction center. Our results call into question the suggested role of ENAQT in the photosynthetic process of green sulfur bacteria and highlight the subtleties associated with drawing lessons for designing biomimetic light-harvesting complexes. PMID- 25141220 TI - Finland: increases in alcohol availability and consumption. AB - This article briefly describes the changes that Finland has undergone during the 1960-2012 period with regards to societal changes, alcohol control policies, alcohol-related harms, and alcohol consumption, after which the findings of the analyses made by Allamani and his colleagues in the AMPHORA project are discussed. It seems that despite the changes in the alcohol field, the strong and comprehensive control policy measures still have a solid footing in the Finnish society. It is also evident that the policy changes implemented over the course of the last decades have affected the development of the total alcohol consumption to a large degree in both positive and negative directions, depending on the kind of measure implemented. PMID- 25141222 TI - Predicting QTc Prolongation in Man From Only In Vitro Data. AB - Mishra et al.(1) in their article "Interaction between domperidone and ketoconazole: toward prediction of consequent QTc prolongation using purely in vitro information" describe the use of physiologically based pharmacokinetic (PBPK) modeling and pharmacodynamic models of cardiac repolarization to predict clinical data from preclinical data. Eliminating the risk of cardiac arrhythmias through delayed repolarization often relies on preclinical data during compound selection. Although there are some limitations, there appears to be significant promise in using this modeling approach. PMID- 25141223 TI - A case of renal cell carcinoma with solitary metastasis to the ovary. PMID- 25141225 TI - Nanoscale wetting and fouling resistance of functionalized surfaces: a computational approach. AB - A computational modeling methodology has been developed and employed to characterize the nanoscale wettability and antifouling properties of functionalized hard and deformable surfaces, with a specific focus on poly(ethylene glycol) grafted substrates and their resistance to graphitic carbons. Empirical evidence suggests that the antifouling behavior of polyethylene PEG is associated with two main mechanisms: steric repulsions and hydration via formation of a structured water layer. However, there is also little attention paid to the contribution of steric repulsion vs surface hydration. We examine these two mechanisms through a combination of in silico contact angle and force measurements at the nanoscale level. We investigate the properties of the grafted functional chains and the underlying substrate, responsible for resisting surface deposition of graphitic contaminants in aqueous solution. Our results reveal that the fouling-release efficiency is enhanced when PEG chains are grafted onto hard hydrophilic substrates such as silica in contrast to deformable polymer substrates where surface modifications are effectively mitigated during interfacial contact with a hard contaminant. We conclude that the contribution of steric repulsion vs surface hydration to the antifouling ability of surfaces is strongly dependent on the nanoscale structure and deformability of the substrate. This generic method can be applied to examine individual contribution of steric repulsions and surface hydration to antifouling performance of grafted chains. PMID- 25141224 TI - Nucleotide-oligomerization-domain-2 affects commensal gut microbiota composition and intracerebral immunopathology in acute Toxoplasma gondii induced murine ileitis. AB - BACKGROUND: Within one week following peroral high dose infection with Toxoplasma (T.) gondii, susceptible mice develop non-selflimiting acute ileitis due to an underlying Th1-type immunopathology. The role of the innate immune receptor nucleotide-oligomerization-domain-2 (NOD2) in mediating potential extra intestinal inflammatory sequelae including the brain, however, has not been investigated so far. METHODOLOGY/PRINCIPAL FINDINGS: Following peroral infection with 100 cysts of T. gondii strain ME49, NOD2-/- mice displayed more severe ileitis and higher small intestinal parasitic loads as compared to wildtype (WT) mice. However, systemic (i.e. splenic) levels of pro-inflammatory cytokines such as TNF-alpha and IFN-gamma were lower in NOD2-/- mice versus WT controls at day 7 p.i. Given that the immunopathological outcome might be influenced by the intestinal microbiota composition, which is shaped by NOD2, we performed a quantitative survey of main intestinal bacterial groups by 16S rRNA analysis. Interestingly, Bifidobacteria were virtually absent in NOD2-/- but not WT mice, whereas differences in remaining bacterial species were rather subtle. Interestingly, more distinct intestinal inflammation was accompanied by higher bacterial translocation rates to extra-intestinal tissue sites such as liver, spleen, and kidneys in T. gondii infected NOD2-/- mice. Strikingly, intracerebral inflammatory foci could be observed as early as seven days following T. gondii infection irrespective of the genotype of animals, whereas NOD2-/- mice exhibited higher intracerebral parasitic loads, higher F4/80 positive macrophage and microglia numbers as well as higher IFN-gamma mRNA expression levels as compared to WT control animals. CONCLUSION/SIGNIFICANCE: NOD2 signaling is involved in protection of mice from T. gondii induced acute ileitis. The parasite-induced Th1 type immunopathology at intestinal as well as extra-intestinal sites including the brain is modulated in a NOD2-dependent manner. PMID- 25141226 TI - Gastrointestinal and respiratory illness in children that do and do not attend child day care centers: a cost-of-illness study. AB - BACKGROUND: Gastrointestinal and respiratory diseases are major causes of morbidity for young children, particularly for those children attending child day care centers (DCCs). Although both diseases are presumed to cause considerable societal costs for care and treatment of illness, the extent of these costs, and the difference of these costs between children that do and do not attend such centers, is largely unknown. OBJECTIVE: Estimate the societal costs for care and treatment of episodes of gastroenteritis (GE) and influenza-like illness (ILI) experienced by Dutch children that attend a DCC, compared to children that do not attend a DCC. METHODS: A web-based monthly survey was conducted among households with children aged 0-48 months from October 2012 to October 2013. Households filled-in a questionnaire on the incidence of GE and ILI episodes experienced by their child during the past 4 weeks, on the costs related to care and treatment of these episodes, and on DCC arrangements. Costs and incidence were adjusted for socioeconomic characteristics including education level, nationality and monthly income of parents, number of children in the household, gender and age of the child and month of survey conduct. RESULTS: Children attending a DCC experienced higher rates of GE (aIRR 1.4 [95%CI: 1.2-1.9]) and ILI (aIRR: 1.4 [95%CI: 1.2 1.6]) compared to children not attending a DCC. The societal costs for care and treatment of an episode of GE and ILI experienced by a DCC-attending child were estimated at ?215.45 [?115.69-?315.02] and ?196.32 [?161.58-?232.74] respectively, twice as high as for a non-DCC-attending child. The DCC attributable economic burden of GE and ILI for the Netherlands was estimated at ?25 million and ?72 million per year. CONCLUSIONS: Although children attending a DCC experience only slightly higher rates of GE and ILI compared to children not attending a DCC, the costs involved per episode are substantially higher. PMID- 25141227 TI - Preparation of highly substituted (beta-acylamino)acrylates via iron-catalyzed alkoxycarbonylation of N-vinylacetamides with carbazates. AB - An efficient iron(II)-catalyzed alkoxycarbonylation reaction between N vinylacetamides and carbazates is reported. The corresponding useful highly substituted (beta-acylamino)acrylates could be obtained in reasonable to good yields and stereoselectivity under mild reaction conditions. PMID- 25141228 TI - Clues for minimal hepatic encephalopathy in children with noncirrhotic portal hypertension. AB - OBJECTIVE: In children with noncirrhotic extrahepatic portal vein obstruction (EHPVO), minimal hepatic encephalopathy (MHE) was reported in a few series, but neither is it routinely investigated nor does consensus about its diagnosis exist. In this prospective observational study we aimed at detecting the prevalence of MHE in children with EHPVO and providing a practical diagnostic protocol. METHODS: A consecutive sample of 13 noncirrhotic children (age range 4 18 years) with EHPVO underwent a screening for MHE based on level of fasting ammonia, quantified electroencephalogram (EEG) evaluation, and a wide battery of 26 psychometric tests exploring learning ability, abstract reasoning, phonemic and semantic fluency, selective attention, executive functions, short-term verbal and visual memory, long-term verbal memory, and visuopractic ability. RESULTS: Five children had at least 2 altered psychometric tests. Selective attention, executive function, and short-term visual memory were the domains more frequently altered, and 4 tests were enough to detect 80% of these children. Fasting ammonia plasma level was increased in 6 children. EEG mean dominant frequency adjusted for age was associated with serum ammonia concentration (beta = -0.44 +/- 0.19, P < 0.05). As a whole, children with EHPVO showed trends for lower alpha (median 41% vs 49%) and higher theta power than controls (median 41% vs 49% and 29% vs 20%, respectively). CONCLUSIONS: MHE affects approximately 50% of children with EHPVO and, therefore, is worthwhile to be investigated. Three simple tools, serum ammonia, quantified EEG, and neuropsychological examination, focused on selective attention, executive function, and short-term visual memory can be used effectively in the evaluation of MHE in this setting. PMID- 25141229 TI - Impact of hiatal hernia on pediatric dyspeptic symptoms. AB - OBJECTIVES: Hiatal hernia (HH) affects from 10% to 50% of adult population. The correlation between HH, gastroesophageal reflux disease, dyspeptic symptoms, and esophagitis has long been known in adults. The primary objective of our prospective observational study was to estimate the prevalence of HH in children undergoing esophagogastroduodenoscopy (EGD), irrespective of their symptoms. METHODS: We prospectively enrolled 111 consecutive children (48 boys and 63 girls; mean age 94.9 +/- 52.3 months) referred for EGD. In all of the patients a symptomatic score assessment based on the Rome III criteria was used to measure frequency, severity, and duration of gastrointestinal symptoms. HH presence was endoscopically defined; esophagitis presence was evaluated either endoscopically and histologically. Children were divided in 2 age-range groups: <48 months (group 1) and >48 months (group 2). RESULTS: Twenty-three patients of 111 (20.7%) had evidence of a sliding HH at EGD. In children from group 2, we found a statistically significant association of HH with heartburn (P = 0.03, 95% confidence interval 1-9.3, r = 0.1) and regurgitation (P = 0.003, 95% confidence interval 1.7-20.4, r = 0.3). Regarding esophagitis presence, no association was found at any age either with defined esophagitis or with dilated intercellular spaces. CONCLUSIONS: Prevalence of HH in our study population was 20.7%. According to our data, HH correlates with the presence of heartburn and regurgitation in children, but not in toddlers. No association was found with esophagitis at any age. PMID- 25141230 TI - gamma-Glutamyl transpeptidase level as a screening marker among diverse etiologies of infantile intrahepatic cholestasis. AB - OBJECTIVES: Low gamma-glutamyl transpeptidase (GGT) level is an important marker for progressive familial intrahepatic cholestasis, yet the cutoff level and clinical application is not well defined. This study aimed to evaluate the role of GGT as a screening marker among diverse etiologies of infantile cholestasis. METHODS: This retrospective study analyzed 256 cholestatic infants admitted to a tertiary referral center between 2000 and 2012. After excluding 121 infants of extrahepatic cholestasis, advanced investigations for 135 infants with intrahepatic cholestasis were performed. The etiologies, outcomes, and correlations with GGT levels were analyzed. Good prognosis was defined as clinical recovery before 1 year of age; poor prognosis as persistent disease, liver transplantation, or death before 1 year. RESULTS: Among 135 patients of intrahepatic cholestasis, >12 different etiologies were found. Neonatal hepatitis (49.6%), progressive familial intrahepatic cholestasis (21.5%), and neonatal cholestasis caused by citrin deficiency (10.4%) were the leading causes. Patients with initial GGT between 75 and 300 U/L had a higher chance of good prognosis (61/74, 82.4%) than those with GGT <75 U/L or >300 U/L (25/61, 41%, P < 0.0001). In the low-GGT group (<= 100 U/L), 52.6% (30/57) of the patients have good prognosis; and GGT level <= 75 U/L has a sensitivity, specificity, and positive predictive value of 100%, 43.3%, and 61.4% in predicting poor prognosis. CONCLUSIONS: Patients with GGT levels <= 75 or >= 300 U/L should receive advanced investigations such as genetic/metabolic assays early; otherwise, the amount of diagnostic workup may be limited if no signs of progressive disease. PMID- 25141232 TI - Acoustic radiation force impulse imaging in paediatric patients: normal liver values. AB - OBJECTIVES: The objective of this study was to obtain a normal value for liver shear wave velocities (SWVs) in healthy paediatric patients and to investigate variations concerning age, sex, and different approaches, depths, and lobes of measurements. METHODS: A total of 150 healthy children (2 months-17 years) were examined with acoustic radiation force impulse (ARFI) technology by an experienced paediatric radiologist, after receiving an informed consent. Measurements obtained were divided according to group age (n = 50, 0-5 years; n = 50, 6-11 years; n = 50, 12-17 years); sex (male-female); lobe (right-left lobe); approach (intercostal-subcostal), and depth of measurements (1-5 and 5-6 cm for the youngest group; 2-6 to 6-8 cm for the 2 other groups). Comparative analyses were performed with measurements obtained at right and left lobes, with different depths and approaches. Differences between age and sex were also analysed. RESULTS: Mean SWV in the right liver lobe was 1.07 +/- 0.10 m/s. No significant differences were found according to sex or among different probe locations. SWVs were, however, significantly higher within left lobe in comparison with right liver lobe (1.07 +/- 0.10 m/s, right; 1.21 +/- 0.16 m/s, left). Depth of measurements also influenced SWV values obtained, being slightly lower at deeper locations. Regarding the age significant differences were found for children <6 years old compared with other age groups. CONCLUSIONS: ARFI analysis seems to be influenced by age, depth, and lobe of measurements. A mean SWV value of 1.07 +/- 0.10 m/s for healthy paediatric population with the possibility of reaching 1.12 m/s in the case of younger children was found. ARFI values were more consistently obtained analysing right liver lobe and depths lower than 5 to 6 cm. PMID- 25141233 TI - Enhanced cycling stability of lithium sulfur batteries using sulfur-polyaniline graphene nanoribbon composite cathodes. AB - A hierarchical nanocomposite material of graphene nanoribbons combined with polyaniline and sulfur using an inexpensive, simple method has been developed. The resulting composite, characterized by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron microscopy, and X-ray diffraction analysis, has a good rate performance and excellent cycling stability. The synergistic combination of electrically conductive graphene nanoribbons, polyaniline, and sulfur produces a composite with high performance. The method developed here is practical for the large-scale development of cathode materials for lithium sulfur batteries. PMID- 25141234 TI - In situ wetting state transition on micro- and nanostructured surfaces at high temperature. AB - We studied the in situ transition of the droplets' wetting state on the heated solid surfaces. The wetting behaviors of four micro- and nanostructured surfaces with different chemical components were studied. These parameters included the maximum contact areas (MCA), the maximum evaporation areas (MEA) and the wetting transition temperature (T(trans)). The reduction in MEAs has a specific transition process from wetting (Wenzel state) or partial wetting (Wenzel-Cassie intermediate state) to nonwetting (Cassie State) as the surface temperature rises. When the MEAs drop to zero at a critical temperature (T(trans)), the droplets rebound from the heated surfaces to complete the wetting transition process. The chemical compounds and the surfaces' rough structure play an important role in the droplets' wetting transition behavior. Before FAS modification, microstructures can increase the MCAs, MEAs, and T(trans). However, the microstructures are less effective at increasing the MEAs and T(trans) than changes to nanostructures. After FAS-modification, both the nano- and microstructures reduce the T(trans). On the FAS-MNSi surfaces, the MEAs are always zero--the droplets rebounded at room temperature, and the wetting transition did occur. We propose two high-temperature mechanisms to explain these transition phenomena. PMID- 25141236 TI - Antiaromatic character of 16 pi electron octaethylporphyrins: magnetically induced ring currents from DFT-GIMIC calculations. AB - The magnetically induced current density susceptibility, also called current density, has been calculated for a recently synthesized octaethylporphyrin (OEP) zinc(II) dication with formally 16 pi electrons. Numerical integration of the current density passing selected chemical bonds yields the current pathway around the porphyrinoid ring and the strength of the ring current. The current strengths show that the OEP-Zn(II) dication is strongly antiaromatic, as also concluded experimentally. The calculation of the ring current pathway shows that all 24 pi electrons participate in the transport of the ring current because the current splits into inner and outer branches of practically equal strengths at the four pyrrolic rings. The corresponding neutral octaethylporphyrinoid without Zn and inner hydrogens is found to be antiaromatic, sustaining a paratropic ring current along the inner pathway with 16 pi electrons. The neutral OEP-Zn(II) molecule with formally 18 pi electrons is found to be almost as aromatic as free-base porphyrin. However, also in this case, all 26 pi electrons contribute to the ring current, as for free-base porphyrin. A comparison of calculated and measured (1)H NMR chemical shifts is presented. The current strength susceptibility under experimental conditions has been estimated by assuming a linear relation between experimental shielding constants and calculated current strengths. PMID- 25141235 TI - Linear population allocation by bistable switches in response to transient stimulation. AB - Many cellular decision processes, including proliferation, differentiation, and phenotypic switching, are controlled by bistable signaling networks. In response to transient or intermediate input signals, these networks allocate a population fraction to each of two distinct states (e.g. OFF and ON). While extensive studies have been carried out to analyze various bistable networks, they are primarily focused on responses of bistable networks to sustained input signals. In this work, we investigate the response characteristics of bistable networks to transient signals, using both theoretical analysis and numerical simulation. We find that bistable systems exhibit a common property: for input signals with short durations, the fraction of switching cells increases linearly with the signal duration, allowing the population to integrate transient signals to tune its response. We propose that this allocation algorithm can be an optimal response strategy for certain cellular decisions in which excessive switching results in lower population fitness. PMID- 25141237 TI - Postprandial oxidative stress and gastrointestinal hormones: is there a link? AB - BACKGROUND: Abnormal postprandial elevation of plasma glucose and lipids plays an important role in the pathogenesis of diabetes and strongly predicts cardiovascular mortality. In patients suffering from type 2 diabetes (T2D) postprandial state is associated with oxidative stress, cardiovascular risk and, probably, with impairment of both secretion and the effect of gastrointestinal peptides. Evaluating postprandial changes of gastrointestinal hormones together with changes in oxidative stress markers may help to understand the mechanisms behind the postprandial state in diabetes as well as suggest new preventive and therapeutical strategies. METHODS: A standard meal test has been used for monitoring the postprandial concentrations of gastrointestinal hormones and oxidative stress markers in patients with T2D (n = 50) compared to healthy controls (n = 50). Blood samples were drawn 0, 30, 60, 120 and 180 minutes after the standard meal. RESULTS: Both basal and postprandial plasma concentrations of glucose and insulin proved to be significantly higher in patients with T2D, whereas plasma concentrations of ghrelin showed significantly lower values during the whole meal test. In comparison with healthy controls, both basal and postprandial concentrations of almost all other gastrointestinal hormones and lipoperoxidation were significantly increased while ascorbic acid, reduced glutathione and superoxide dismutase activity were decreased in patients with T2D. A positive relationship was found between changes in GIP and those of glucose and immunoreactive insulin in diabetic patients (p<0.001 and p<0.001, respectively) and between changes in PYY and those of glucose (p<0.01). There was a positive correlation between changes in GIP and PYY and changes in ascorbic acid in patients with T2D (p<0.05 and p<0.001, respectively). CONCLUSION/INTERPRETATION: Apart from a positive relationship of postprandial changes in GIP and PYY with changes in ascorbic acid, there was no direct link observed between gastrointestinal hormones and oxidative stress markers in diabetic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01572402. PMID- 25141239 TI - Gut microbiota and inflammatory bowel disease: the role of antibiotics in disease management. AB - Imbalances in the composition and number of bacteria in the gut microbiota have been implicated in inflammatory bowel disease (IBD), and modulation of the gut microbiota by probiotics and antibiotics in IBD has been an active area of research, with mixed results. This narrative review summarizes the findings of relevant publications identified using the PubMed database. Although antibiotics have been associated with an increased risk of IBD development and flares, several meta-analyses demonstrate that antibiotics are efficacious for the induction of remission and treatment of flares in patients with IBD. Data supporting their use include a large number of antibiotic studies in Crohn's disease and evidence suggests antibiotics are efficacious in both Crohn's disease and ulcerative colitis, although there are fewer studies of the latter. For Crohn's disease, antibiotics have been shown to be useful for the induction of remission and in the postoperative management of patients undergoing surgery. Additionally, patients with fistulizing disease, particularly perianal, can benefit from antibiotics administered short term. Both antimicrobials and probiotics have been shown to be useful for the treatment of pouchitis. Additional randomized controlled trials are needed to further elucidate the role of bacteria in IBD and to better inform clinicians about appropriate antibiotic therapies. PMID- 25141238 TI - Proteomic characterization of Helicobacter pylori CagA antigen recognized by child serum antibodies and its epitope mapping by peptide array. AB - Serum antibodies against pathogenic bacteria play immunologically protective roles, and can be utilized as diagnostic markers of infection. This study focused on Japanese child serum antibodies against Helicobacter pylori, a chronically infected gastric bacterium which causes gastric cancer in adults. Serological diagnosis for H. pylori infection is well established for adults, but it needs to be improved for children. Serum samples from 24 children, 22 H. pylori (Hp) positive and 2 Hp-negative children, were used to catalogue antigenic proteins of a Japanese strain CPY2052 by two-dimensional electrophoresis followed by immunoblot and LC-MS/MS analysis. In total, 24 proteins were identified as candidate antigen proteins. Among these, the major virulence factor, cytotoxin associated gene A protein (CagA) was the most reactive antigen recognized by all the Hp-positive sera even from children under the age of 3 years. The major antigenic part of CagA was identified in the middle region, and two peptides containing CagA epitopes were identified using a newly developed peptide/protein combined array chip method, modified from our previous protein chip method. Each of the epitopes was found to contain amino acid residue(s) unique to East Asian CagA. Epitope analysis of CagA indicated importance of the regional CagA antigens for serodiagnosis of H. pylori infection in children. PMID- 25141240 TI - Comparison of subjective effects of extended-release versus immediate-release oxycodone/acetaminophen tablets in healthy nondependent recreational users of prescription opioids: a randomized trial. AB - BACKGROUND: Prescription opioids have substantial abuse potential. This study compared the positive subjective drug effects of a newly developed extended release (ER) oxycodone (OC)/acetaminophen (acetyl-para-aminophenol [APAP]) formulation with those of immediate-release (IR) OC/APAP. METHODS: This randomized, double-blind, active- and placebo-controlled, 7-way crossover study enrolled healthy volunteers who were recreational prescription opioid users. The protocol was approved by an institutional review board and all participants provided written informed consent. Participants received single doses of intact ER and IR OC/APAP 15/650 mg, intact ER and IR OC/APAP 30/1300 mg, crushed ER and IR OC/APAP 30/1300 mg, and placebo. Peak subjective effects (Emax), time to Emax, and area under the drug-effect curves for drug liking, drug high, and good drug effects were measured using visual analogue scales. Least squares means with 95% confidence interval were compared using analysis of variance. RESULTS: Among completers (N = 55), intact ER OC/APAP produced delayed and lower peak effects versus IR OC/APAP. Comparing intact tablets, the drug liking Emax (least squares means [95% confidence interval]) was significantly lower for OC/APAP 30/1300 mg (76.4 [72.8 to 80.0]) than for IR OC/APAP 30/1300 mg (85.6 [81.9 to 89.2]; difference, -9.2 [-13.1 to -5.2]; P < 0.001). Similar results were observed for intact ER and IR OC/APAP (15 mg/650 mg). Crushing ER OC/APAP 30/1300 mg further delayed these effects compared with the same dose of crushed IR OC/APAP and intact ER OC/APAP. CONCLUSIONS: Extended-release OC/APAP produced lower subjective drug effects than IR OC/APAP. Crushing ER OC/APAP further delayed onset of subjective effects compared with intact ER OC/APAP. The ER OC/APAP may be less attractive for abuse than IR OC/APAP. CLINICAL TRIAL REGISTRATION: This phase 1 study conducted in the United States was not registered. PMID- 25141241 TI - Esomeprazole treatment of frequent heartburn: two randomized, double-blind, placebo-controlled trials. AB - PURPOSE: To determine the efficacy of a 14-day regimen of esomeprazole 20 mg for the treatment of frequent heartburn in subjects who are likely to self-treat with over-the-counter medications without consulting a health care provider. METHODS: Adults with frequent heartburn >= 2 days per week in the past 4 weeks were randomly assigned to 14-day double-blind treatment with esomeprazole 20 mg once daily or placebo in 2 identical multicenter studies (ClinicalTrials.gov identifiers: NCT01370525, NCT01370538). The primary efficacy outcome was percentage of heartburn-free 24-hour days across 14 days. Secondary efficacy outcomes included heartburn resolution, defined as heartburn <= 2 days over 14 days, and percentages of subjects reporting <= 1 day with heartburn in the first and final weeks of treatment. Subjects recorded data in daily self-assessment diaries. RESULTS: The percentage of heartburn-free 24-hour days over 14 days was significantly higher (P < 0.0001) in subjects receiving esomeprazole 20 mg compared with placebo in study 1 (N = 331; 46.13% vs. 33.07%, respectively) and study 2 (N = 320; 48.00% vs 32.75%, respectively). Significantly more subjects treated with esomeprazole 20 mg had heartburn resolution over 14 days and in the first and final weeks compared with placebo. Within the first 4 days, the proportion of subjects with heartburn-free days was significantly greater with esomeprazole 20 mg versus placebo. Treatment was generally well tolerated, with a safety pattern consistent with the known profile for esomeprazole. CONCLUSION: A 14-day regimen of esomeprazole 20 mg once daily was effective for treating frequent heartburn in subjects who are likely to self-treat with over-the-counter medications. PMID- 25141242 TI - A review of the literature on multiple factors involved in postoperative pain course and duration. AB - OBJECTIVE: To review the literature on the progression from acute to chronic postoperative pain, to evaluate the evidence for the risk of progressing to persistent postoperative and chronic pain, and to identify characteristics of pharmacologic treatments to best tailor therapy to an individual patient's pain profile. BACKGROUND: Pain is most commonly classified by duration (acute, chronic) and pathophysiology (nociceptive, neuropathic); however, these descriptors alone incompletely describe pain. Additionally, the transition between acute and chronic postoperative pain is not well understood. METHODS: We conducted a qualitative review and evaluation of the literature on postoperative pain with respect to the above objectives. RESULTS: Individualized pharmacologic treatments require a complete characterization of a patient's pain profile, in terms of frequency of pain over the course of a 24-hour day and over time thereafter, frequency and duration of pain flares, and presence of neuropathic pain. These considerations can help guide the choice of pharmacologic treatment to meet patient needs over a 24-hour day and over time after surgery. With respect to opioid analgesics, acute pain requires rapid onset of analgesia and the ability to titrate analgesia to the changing characteristics of pain over a short period. For these reasons, short-acting opioid analgesics have been preferred; however, there are opioid formulations with rapid onset and extended release for reduced dosing frequency. Although nociceptive pain can typically be controlled by titration of the dose of an opioid analgesic, neuropathic pain may respond better to the addition of an antineuropathic medication rather than to opioid dose escalation. CONCLUSION: Advances in individualized pharmacologic treatment for postoperative pain have resulted in better pain control. Moreover, the recognition of sub-acute pain as a new entity is important because many surgical patients will need therapy beyond the first 8 days after surgery. In this group of patients the diagnosis of a neuropathic pain component will be important so that appropriate multimodal therapy may be implemented. PMID- 25141243 TI - The economic burden of diagnosed opioid abuse among commercially insured individuals. AB - The abuse of prescription opioids imposes a substantial public health and economic burden. Recent research using administrative claims data has substantiated the prevalence and cost of opioid abuse among commercially insured individuals. Although administrative claims data are readily available and have been used to effectively answer research questions about the burden of illness for many different conditions, an important issue is the reliability, replicability, and generalizability of estimates derived from different databases. Therefore, this study sought to assess whether the findings of a recently published study of opioid abuse in a commercial claims database (original analysis) could be replicated in a different commercial claims database. The original analysis, which analyzed the prevalence and excess health care costs of diagnosed opioid abuse in the OptumHealth Reporting and Insights Database, was replicated by applying the same approach to the Truven MarketScan Commercial Claims and Encounters Database (replication analysis). In the replication analysis, the prevalence of diagnosed opioid abuse increased steadily from 15.8 diagnosed opioid abusers per 10,000 in 2009, to 26.6 diagnosed opioid abusers per 10,000 in 2012. Although the prevalence of diagnosed opioid abuse was higher than reported in the original analysis, the trend of increasing prevalence over time was consistent across analyses. Additionally, diagnosed abusers had excess annual per patient health care costs of $11,376 in the replication analysis, which was consistent with the excess annual per patient health care costs of diagnosed abuse of $10,627 reported in the original analysis. The replication analysis also found an upward trend in the prevalence of diagnosed opioid abuse over time and substantial excess annual per patient health care costs of diagnosed opioid abuse among commercially insured individuals, suggesting that these findings are generalizable to other commercially insured populations. PMID- 25141244 TI - Acute pain: effective management requires comprehensive assessment. AB - Pain is among the most common reasons that patients seek medical care, and inadequate assessment may result in suboptimal management. Acute pain in response to trauma or surgery can be complex, variable, and dynamic, but its assessment is often simplistic and brief. One-dimensional rating scale measures of pain severity facilitate rapid evaluation and often form the basis of treatment algorithms. However, additional features of pain should inform the selection of a treatment regimen, and can include pain qualities, duration, impact on functional capabilities, and underlying cause. Patient age, sex, psychosocial features, and comorbid conditions are also important features to consider. Use of a multidimensional tool is recommended for assessing many of these features if time permits. Additionally, clinicians often fail to recognize or consider the potentially detrimental long-term effects of acute pain. As the United States continues to experience a prescription drug crisis, a "universal precautions" approach including abuse risk assessment and abuse deterrence strategies should be implemented for patients receiving opioids. Increased efforts and research are necessary to enhance the utility of available acute pain assessment tools. Developing more comprehensive tools for patient assessment is the first step in achieving the ultimate goal of effective acute pain management. The objectives of this review are to summarize issues regarding the complexity of acute pain and to provide suggestions for its evaluation. PMID- 25141245 TI - Optimal treatment of anaphylaxis: antihistamines versus epinephrine. AB - Anaphylaxis is a rapid, systemic, often unanticipated, and potentially life threatening immune reaction occurring after exposure to certain foreign substances. The main immunologic triggers include food, insect venom, and medications. Multiple immunologic pathways underlie anaphylaxis, but most involve immune activation and release of immunomodulators. Anaphylaxis can be difficult to recognize clinically, making differential diagnosis key. The incidence of anaphylaxis has at least doubled during the past few decades, and in the United States alone, an estimated 1500 fatalities are attributed to anaphylaxis annually. The increasing incidence and potentially life-threatening nature of anaphylaxis coupled with diagnostic challenges make appropriate and timely treatment critical. Epinephrine is universally recommended as the first-line therapy for anaphylaxis, and early treatment is critical to prevent a potentially fatal outcome. Despite the evidence and guideline recommendations supporting its use for anaphylaxis, epinephrine remains underused. Data indicate that antihistamines are more commonly used to treat patients with anaphylaxis. Although histamine is involved in anaphylaxis, treatment with antihistamines does not relieve or prevent all of the pathophysiological symptoms of anaphylaxis, including the more serious complications such as airway obstruction, hypotension, and shock. Additionally, antihistamines do not act as rapidly as epinephrine; maximal plasma concentrations are reached between 1 and 3 hours for antihistamines compared with < 10 minutes for intramuscular epinephrine injection. This demonstrates the need for improved approaches to educate physicians and patients regarding the appropriate treatment of anaphylaxis. PMID- 25141246 TI - Risk of upper gastrointestinal ulcers in patients with osteoarthritis receiving single-tablet ibuprofen/famotidine versus ibuprofen alone: pooled efficacy and safety analyses of two randomized, double-blind, comparison trials. AB - BACKGROUND: Although anti-inflammatory doses of ibuprofen are very effective in treating the signs and symptoms of osteoarthritis (OA), they come with an increased risk for gastrointestinal damage which can limit their use and decrease patient adherence to therapy. OBJECTIVE: Assess the efficacy and safety of an ibuprofen/famotidine fixed-dose tablet for reducing the risk of upper gastrointestinal (UGI) ulcers compared with ibuprofen alone in OA patients. METHODS: Osteoarthritis patients from previously completed randomized, double blind, comparison registration trials (REDUCE-1 and 2) which included a broad pain patient population, were pooled and analyzed for (1) the risk of endoscopically identified UGI ulcers over 24 weeks and (2) comparative pre specified treatment emergent adverse events (TEAEs). The primary outcomes were the comparative incidence of UGI, gastric, and duodenal ulcers and TEAEs in (1) the total OA population, (2) those aged >= 60 years, and (3) those on low dose aspirin. A total of 776 patients were randomized (safety population), and 713 were evaluable as the study population. RESULTS: Upper gastrointestinal ulcer risk was statistically significantly reduced with the fixed dose tablet compared with ibuprofen alone by 44% in the overall population, 55% in those aged >= 60 years and 65% in those on low dose aspirin. Individually, gastric and duodenal ulcers were also significantly reduced in all groups analyzed. Adverse events of special interest were generally similar between the 2 groups, with the exception of dyspepsia. Relative risk reduction for dyspepsia in the overall population was 40% and 55% in those aged >= 60 years. Patients not receiving low dose aspirin had a 49% relative risk reduction in dyspepsia. CONCLUSION: The fixed combination of ibuprofen/famotidine significantly reduced the risk for endoscopically documented gastrointestinal ulcers in OA patients and produced clinically meaningful reductions in patient reported dyspepsia compared with the ibuprofen alone. PMID- 25141247 TI - Role of indomethacin in acute pain and inflammation management: a review of the literature. AB - Nonsteroidal anti-inflammatory drugs are a class of analgesics that includes traditional nonselective and selective cyclooxygenase-2 inhibitors that block the biosynthesis of prostaglandins and thromboxane. Indomethacin is a nonsteroidal anti-inflammatory drug with potent antipyretic, analgesic, and anti-inflammatory activity that has been effectively used in the management of mild-to-moderate pain since the mid-1960s. It is commonly prescribed for the relief of acute gouty arthritis pain, but has demonstrated efficacy in the treatment of various other painful conditions. Numerous comparative studies have affirmed the clinical utility of indomethacin relative to other widely used analgesics. This review provides an historic overview of indomethacin and its efficacy compared with other commonly used analgesics, and discusses new indomethacin drug products. PMID- 25141249 TI - Chronic pelvic pain syndrome: a clinical enigma. AB - Chronic nonbacterial prostatitis is an ill-defined, painful clinical condition that is characterized by various nonspecific symptoms, some of which are related to urination or the male reproductive organs. Urologists diagnose this particular condition when the symptoms are not associated with urinary bacterial growth before and after transrectal prostate massage. In this review, we describe the recommended and optional tests that can be performed in these cases. There is significant overlap between chronic nonbacterial prostatitis and other unexplained pain conditions, raising the question as to whether the prostate is the culprit. The sources and mediators of pain and the psychological aspects of this complex condition are discussed. Treatments consist of traditional antibiotics and alpha-blockers. Because the pain relief is often temporary, patients seek other solutions. Various therapeutics have been introduced to satisfy the expectations of patients and physicians. We discuss other pain medications, as well as intraprostatic drug injections and shockwave therapy. Importantly, however, not all of these suggestions have been widely accepted by urologists or pain clinics. PMID- 25141248 TI - Combining opioid and adrenergic mechanisms for chronic pain. AB - Chronic pain is a highly prevalent medical problem in the United States. Although opioids and serotonin-norepinephrine reuptake inhibitors (SNRIs) have demonstrated efficacy for relief of chronic pain, each has risks of adverse events in patients. Because of the risk of opioid abuse and addiction, combinations reducing opioid requirements are particularly valuable. Opioid and SNRI agents relieve pain by different pathways; concurrent use of each agent separately offers many potential benefits: complementary and possibly synergistic analgesic efficacy, separate titrations of opioid and SNRI effects, and the reduction of opioid requirements. However, few clinical studies have investigated the ideal ratios for combinations of opioids and SNRIs. A number of factors affect whether specific combinations have additive, synergistic, less than additive efficacy, or increase adverse events in patients, including general pharmacokinetic considerations, the potential for pharmacodynamic drug interactions, dose, and timing. Because there is little clinical evidence guiding combination therapy with separate opioid and SNRI agents, using single-molecule agents provides safe and effective therapy and should be the first option presented to patients. The use of empiric combinations of separate opioid and SNRI combinations needs to be considered in light of clinical cautions, including the lack of published evidence to guide dose conversion from any opioid to tramadol or to tapentadol, and vice versa; the need to avoid combinations with known drug interactions; and the need to titrate the dose when adding an SNRI to an opioid, and vice versa. PMID- 25141250 TI - The management of acute hypertension in patients with renal dysfunction: labetalol or nicardipine? AB - STUDY OBJECTIVES: To compare the safety and efficacy of U.S. Food and Drug Administration (FDA)-recommended doses of labetalol and nicardipine for hypertension (HTN) management in a subset of patients with renal dysfunction (RD). DESIGN: Randomized, open label, multicenter prospective clinical trial. SETTING: Thirteen United States tertiary care emergency departments. PATIENTS OR PARTICIPANTS: Subgroup analysis of the Evaluation of IV Cardene (Nicardipine) and Labetalol Use in the Emergency Department (CLUE) clinical trial. The subjects were 104 patients with RD (i.e., creatinine clearance < 75 mL/min) who presented to the emergency department with a systolic blood pressure (SBP) >= 180 mmHg on 2 consecutive readings and for whom the emergency physician felt intravenous antihypertensive therapy was desirable. INTERVENTIONS: The FDA recommended doses of either labetalol or nicardipine for HTN management. MEASUREMENTS: The number of patients achieving the physician's predefined target SBP range within 30 minutes of treatment. RESULTS: Patients treated with nicardipine were within target range more often than those receiving labetalol (92% vs. 78%, P = 0.046). On 6 SBP measures, patients treated with nicardipine were more likely to achieve the target range on either 5 or all 6 readings than were patients treated with labetalol (46% vs. 25%, P = 0.024). Labetalol patients were more likely to require rescue medication (27% vs. 17%, P = 0.020). Adverse events thought to be related to either treatment group were not reported in the 30-minute active study period, and patients had slower heart rates at all time points after 5 minutes (P < 0.01). CONCLUSIONS: In severe HTN with RD, nicardipine-treated patients are more likely to reach a target blood pressure range within 30 minutes than are patients receiving labetalol. CLINICAL IMPLICATIONS: Within 30 minutes of administration, nicardipine is more efficacious than labetalol for acute blood pressure control in patients with RD. PMID- 25141251 TI - Quality of life after laparoscopic adjustable gastric banding (LAP-BAND): APEX interim 3-year analysis. AB - BACKGROUND: Obesity is often associated with diminished health-related quality of life (HRQOL), but significant gains in HRQOL have been observed after bariatric surgery. Laparoscopic adjustable gastric banding has been established as a safe, effective treatment to reduce weight in patients with obesity. This report summarizes interim 3-year changes in HRQOL and body weight, as well as safety postimplantation of the LAP-BAND AP (LBAP) system. METHODS: The LAP-BAND AP EXperience (APEX) trial, an ongoing, prospective, 5-year, open-label study, assessed changes in HRQOL (Obesity and Weight-Loss Quality of Life [OWLQOL] questionnaire) and body weight, and safety after placement of LBAP. This interim analysis represents patients with evaluable OWLQOL data at baseline and at 3 years (n = 183). RESULTS: The OWLQOL total score and individual scores significantly improved within 6 months post-LBAP and continued to improve during a 3 year period (P < 0.0001, both). Total score improved from 71.0 to 34.0 (mean improvement from baseline, 52%; range, 18%-65%); mean change in individual scores was -2.2 (range, -0.7 to -3.0). Percent weight loss was maintained through 3 years (19.4%; n = 174). Improvement in OWLQOL was associated with percent weight loss at 3 years (r = -0.5407; P < 0.0001). Revisions and explants were performed in 7 (3.8%) and 20 (10.9%) out of 183 patients, respectively. CONCLUSIONS: Meaningful improvement in quality of life occurred through clinically significant weight loss after LBAP placement, extending throughout the 3 years of this analysis. PMID- 25141252 TI - Improving early-stage diagnosis and management of COPD in primary care. AB - Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease, but it often remains undetected in its mild and moderate forms. Patients frequently remain undiagnosed and untreated until the disease has become severe and debilitating, greatly impacting their quality of life. Primary care physicians (PCPs) are most often the first point of contact, and therefore they are in the best position to identify patients at risk of COPD in the early stages. Consequently, they play a critical role in the management of the disease, particularly smoking cessation. One of the earliest symptoms is activity-related dyspnea and subsequent exercise intolerance, often compensated for by reduction in physical activity. This review addresses the approaches used to identify COPD in the primary care setting, including simple tools such as handheld spirometers and questionnaires. A recent study demonstrated that, compared with usual care, use of the COPD Population Screener questionnaire alone and in combination with the copd-6 handheld spirometer significantly improved the odds of referral of patients with suspected COPD for pulmonary function testing or to a pulmonologist. Identification of patients suspected of having the disease and differentiation of COPD from asthma are important in order that treatment can be initiated in the mild stages to slow or prevent disease progression and reduce the risk of exacerbations. The review also discusses the evidence to date on pharmacologic treatment using short-acting and long-acting anticholinergics and beta2-agonists, and nonpharmacologic interventions, such as smoking cessation, pulmonary rehabilitation, and influenza and pneumococcal vaccination in patients with mild and moderate COPD. PMID- 25141253 TI - Attention-deficit/hyperactivity disorder, iron deficiency, and obesity: is there a link? AB - The exact etiopathophysiology of attention-deficit/hyperactivity disorder (ADHD) remains elusive, likely because of its phenotypic heterogeneity. Given the involvement of iron in neurocognitive and behavioral functions, iron deficiency (ID) has been suggested as a possible etiopathophysiological factor in a subsample of individuals with ADHD. Most studies assessing ID in ADHD have focused on serum ferritin, a marker of peripheral iron status. Results from these studies are mixed, and the largest studies failed to find a significant association between ADHD and low serum ferritin levels. However, serum ferritin may be influenced by several conditions, including inflammatory status. Increasing evidence, especially from epidemiological studies, points to a significant association between ADHD and obesity. Interestingly, obesity is associated with a chronic inflammatory status, characterized by ID with normal-to high serum ferritin levels. This article reviews the literature on iron status in ADHD and on the relationship between ADHD and obesity; discusses a possible link among ADHD, ID, and obesity; and proposes that comorbid obesity contributes to ID, via chronic inflammation, in a subsample of individuals with ADHD. Thus, the comorbidity between ADHD and obesity suggests moving beyond serum ferritin levels and assessing the molecular pathways of chronic inflammation that lead to ID in individuals with ADHD and obesity. In turns, this may pave the way for novel treatment strategies for cognitive and behavioral dysfunctions related to ID in ADHD. PMID- 25141254 TI - Management of diabetic nephropathy in older patients: a need for flexible guidelines. AB - As the population ages and diabetes mellitus increases in prevalence, the incidence of diabetic nephropathy (DN) is becoming a disease of older people (aged >= 75 years). As the epidemiology of diabetes mellitus and DN shifts toward this patient population, the pathogenesis of DN in old age is changing: the pathologic findings suggest ischemia and hypertension, and the classic Kimmelstiel-Wilson lesions may be absent. The demographic shift in the epidemiology and the associated changes in pathology because of aging and atherosclerosis will have a significant impact on various aspects related to the disease in old age. This article reviews the authors' current understanding of DN and its implications on clinical management relevant to current guidelines. PMID- 25141255 TI - Metabolic syndrome prevalence among Northern Mexican adult population. AB - BACKGROUND AND AIMS: Dietary habits in the Mexican population have changed dramatically over the last few years, which are reflected in increased overweight and obesity prevalence. The aim was to examine the prevalence of metabolic syndrome (MetS) and associated risk factors in Northern Mexican adults aged >= 16 years. METHODS AND RESULTS: The study was a population-based cross-sectional nutritional survey carried out in the State of Nuevo Leon, Mexico. The study included a sub-sample of 1,200 subjects aged 16 and over who took part in the State Survey of Nutrition and Health-Nuevo Leon 2011/2012. Anthropometric measurements, physical activity, blood pressure and fasting blood tests for biochemical analysis were obtained from all subjects. The prevalence of MetS in Mexican adults aged >= 16 years was 54.8%, reaching 73.8% in obese subjects. This prevalence was higher in women (60.4%) than in men (48.9%) and increased with age in both genders. Multivariate analyses showed no evident relation between MetS components and the level of physical activity. CONCLUSIONS: Obese adults, mainly women, are particularly at risk of developing MetS, with the associated implications for their health. The increasing prevalence of MetS highlights the need for developing strategies for its early detection and prevention. PMID- 25141256 TI - [Sociocultural and medical management of hypertension in sub-Saharan Africa]. AB - Hypertension has now become very prevalent in sub-Saharan Africa, in part due to the region's epidemiologic transition. Its long asymptomatic onset explains its late recognition and thus the high frequency of complications. Sociocultural conditions play an important role in the genesis of the disease in this region and in the difficulties encountered in its management. The breakdown of traditional ways of life, growing urbanization, and the switch to a western lifestyle and diet all have well-known deleterious effects on the cardiovascular system. High salt consumption, sedentarity, overweight and alcohol intake all promote these developments. The insufficient availability of medical care, poverty, and poor understanding of chronic diseases complicate the medical management of hypertension. In these regions, it is now a public health challenge that requires the training of healthcare workers and the involvement of the society as a whole, including political decisions, health education for school children, and actions by social organizations and local officials and leaders. This communication must always respect traditional customs. Both curative measures and preventive actions are essential. Priority must be given to combatting excessive salt consumption, for the results of its reduction are known to be rapid and positive. Preventing or reducing overweight and obesity, sedentarity, and alcohol and tobacco consumption are effective steps against hypertension, but also atheromatous cardiovascular diseases and diabetes. Drug therapy must meet the three essential criteria: it must be effective, available, and inexpensive. Hypertension is not inevitable, but reflects changes in society. It appears to be transmitted in part by modern lifestyles, which can be modified. PMID- 25141259 TI - Flexible graphene electrode-based organic photovoltaics with record-high efficiency. AB - Advancements in the field of flexible high-efficiency solar cells and other optoelectronic devices will strongly depend on the development of electrode materials with good conductivity and flexibility. To address chemical and mechanical instability of currently used indium tin oxide (ITO), graphene has been suggested as a promising flexible transparent electrode but challenges remain in achieving high efficiency of graphene-based polymer solar cells (PSCs) compared to their ITO-based counterparts. Here we demonstrate graphene anode- and cathode-based flexible PSCs with record-high power conversion efficiencies of 6.1 and 7.1%, respectively. The high efficiencies were achieved via thermal treatment of MoO3 electron blocking layer and direct deposition of ZnO electron transporting layer on graphene. We also demonstrate graphene-based flexible PSCs on polyethylene naphthalate substrates and show the device stability under different bending conditions. Our work paves a way to fully graphene electrode based flexible solar cells using a simple and reproducible process. PMID- 25141257 TI - Pharmacokinetics-pharmacodynamics analysis of bicyclic 4-nitroimidazole analogs in a murine model of tuberculosis. AB - PA-824 is a bicyclic 4-nitroimidazole, currently in phase II clinical trials for the treatment of tuberculosis. Dose fractionation pharmacokinetic-pharmacodynamic studies in mice indicated that the driver of PA-824 in vivo efficacy is the time during which the free drug concentrations in plasma are above the MIC (fT>MIC). In this study, a panel of closely related potent bicyclic 4-nitroimidazoles was profiled in both in vivo PK and efficacy studies. In an established murine TB model, the efficacy of diverse nitroimidazole analogs ranged between 0.5 and 2.3 log CFU reduction compared to untreated controls. Further, a retrospective analysis was performed for a set of seven nitroimidazole analogs to identify the PK parameters that correlate with in vivo efficacy. Our findings show that the in vivo efficacy of bicyclic 4-nitroimidazoles correlated better with lung PK than with plasma PK. Further, nitroimidazole analogs with moderate-to-high volume of distribution and Lung to plasma ratios of >2 showed good efficacy. Among all the PK-PD indices, total lung T>MIC correlated the best with in vivo efficacy (rs = 0.88) followed by lung Cmax/MIC and AUC/MIC. Thus, lung drug distribution studies could potentially be exploited to guide the selection of compounds for efficacy studies, thereby accelerating the drug discovery efforts in finding new nitroimidazole analogs. PMID- 25141261 TI - Adenovirus-mediated FKHRL1/TM sensitizes melanoma cells to apoptosis induced by temozolomide. AB - Melanoma exhibits variable resistance to the alkylating agent temozolomide (TMZ). We evaluated the potential of adenovirus expressing forkhead human transcription factor like 1 triple mutant (Ad-FKHRL1/TM) to sensitize melanoma cells to TMZ. Four melanoma cell lines were treated with Ad-FKHRL1/TM and TMZ, alone or in combination. Apoptosis was assessed by activation and inhibition of caspase pathway, nuclei fragmentation, and annexin V staining. The potential therapeutic efficacy of Ad-FKHRL1/TM with TMZ was also assessed in a mouse melanoma xenograft model. Combination therapy of Ad-FKHRL1/TM and TMZ resulted in greater cell killing (<20% cell viability) compared to single therapy and controls (p<0.05). Combination indices of Ad-FKHRL1/TM and TMZ therapy indicated significant (p<0.05) synergistic killing effect. Greater apoptosis induction was found in cells treated with Ad-FKHRL1/TM and TMZ than Ad-FKHRL1/TM or TMZ-treated cells alone. Treatment with temozolomide enhanced adenovirus transgene expression in a cell type-dependent manner. In an in vivo model, combination therapy of Ad FKHRL1/TM with TMZ results in greater tumor growth reduction in comparison with single treatments. We suggest that Ad-FKHRL1/TM is a promising vector to sensitize melanoma cells to TMZ, and that a combination of both approaches would be effective in the clinical setting. PMID- 25141260 TI - Cross-linking electrochemical mass spectrometry for probing protein three dimensional structures. AB - Chemical cross-linking combined with mass spectrometry (MS) is powerful to provide protein three-dimensional structure information but difficulties in identifying cross-linked peptides and elucidating their structures limit its usefulness. To tackle these challenges, this study presents a novel cross-linking MS in conjunction with electrochemistry using disulfide-bond-containing dithiobis[succinimidyl propionate] (DSP) as the cross-linker. In our approach, electrolysis of DSP-bridged protein/peptide products, as online monitored by desorption electrospray ionization mass spectrometry is highly informative. First, as disulfide bonds are electrochemically reducible, the cross-links are subject to pronounced intensity decrease upon electrolytic reduction, suggesting a new way to identify cross-links. Also, mass shift before and after electrolysis suggests the linkage pattern of cross-links. Electrochemical reduction removes disulfide bond constraints, possibly increasing sequence coverage for tandem MS analysis and yielding linear peptides whose structures are more easily determined than their cross-linked precursor peptides. Furthermore, this cross-linking electrochemical MS method is rapid, due to the fast nature of electrochemical conversion (much faster than traditional chemical reduction) and no need for chromatographic separation, which would be of high value for structural proteomics research. PMID- 25141262 TI - Epigenetic alterations and autoimmune disease. AB - Recent advances in epigenetics have enhanced our knowledge of how environmental factors (UV radiation, drugs, infections, etc.) contribute to the development of autoimmune diseases (AID) in genetically predisposed individuals. Studies conducted in monozygotic twins discordant for AID and spontaneous autoimmune animal models have highlighted the importance of DNA methylation changes and histone modifications. Alterations in the epigenetic pattern seem to be cell specific, as CD4+ T cells and B cells are dysregulated in systemic lupus erythematosus, synovial fibroblasts in rheumatoid arthritis and cerebral cells in multiple sclerosis. With regard to lymphocytes, the control of tolerance is affected, leading to the development of autoreactive cells. Other epigenetic processes, such as the newly described miRNAs, and post-translational protein modifications may also be suspected. Altogether, a conceptual revolution is in progress, in AID, with potential new therapeutic strategies targeting epigenetic patterns. PMID- 25141263 TI - Decreased urine albumin:creatinine ratios in infants of diabetic mothers: does exposure to diabetic pregnancies alter fetal renal development? AB - Offspring of diabetic mothers experience an increased risk for type 2 diabetes but it is not known whether diabetic pregnancies also confer a higher inter generational risk for diabetic complications. Because microalbuminuria is a sensitive indicator of glomerular damage, we compared the urine albumin:creatinine ratios (ACRs) between 65 infants of diabetic mothers (InfDM+) and 59 infants of non-diabetic mothers (InfDM-), and repeated the comparisons in 21 InfDM+ and 19 InfDM- when children were 5-19 months old. ACRs were higher among neonates compared with normal reference values for adults, but declined with increasing age. The only independent predictor of higher ACRs in a logistic regression model (?13 mg/mmol v. <13 mg/mmol) was the presence of delivery complications (odds ratio 2.95; P = 0.015). Neither high nor low birth weight was associated with higher neonatal ACRs. The most unique finding of the study was that InfDM+ had significantly lower ACRs than InfDM- [mean = 12.9 (median = 6.0) v. mean = 16.6 (median = 11.5), respectively at P = 0.05] even after adjusting for other variables using logistic regression (odds ratio 0.25; P = 0.001). In contrast, by 5-19 months, there was a trend toward higher ACRs among InfDM+ compared with InfDM- [mean = 6.3 mg/mmol (median = 1.9) v. mean = 3.0 mg/mmol (median = 2.5), respectively at P = 0.25]. Lower ACRs in InfDM+ may be due to developmental changes in fetal kidneys induced by hyperinsulinemia. Although the implications of this observation are unclear, it is possible that exposure to a diabetic intrauterine environment might influence the later risk for renal disease. PMID- 25141264 TI - Osteoprotegerin in pregnant adolescents differs by race and is related to infant birth weight z-score. AB - Osteoprotegerin (OPG) is involved in the regulation of bone turnover, but little is known about this protein during pregnancy or among neonates. We undertook a prospective longitudinal study to identify relationships between OPG, markers of bone turnover and birth outcomes in 155 pregnant adolescents (13-18 years) and their newborns. Maternal blood samples were collected at mid-gestation and at delivery. Cord blood was obtained at delivery. Serum OPG, estradiol and markers of bone formation (osteocalcin) and resorption (N-telopeptide) were assessed in all samples. Placental OPG expression was assessed in placental tissue obtained at delivery. Bone markers and OPG increased significantly from mid-gestation (26.0 +/- 3.4 weeks) to delivery (39.3 +/- 2.6 weeks). Neonatal OPG was significantly lower, but bone turnover markers were significantly higher than maternal values at mid-gestation and at parturition (P < 0.001). African-American adolescents had higher concentrations of OPG than Caucasian adolescents at mid gestation (P = 0.01) and delivery (P = 0.04). Gestational age and estradiol were also predictors of maternal OPG at mid-gestation and delivery. OPG concentrations in cord blood were correlated with maternal OPG concentrations and were negatively associated with infant birth weight z-score (P = 0.02) and ponderal index (P = 0.02). In conclusion, maternal OPG concentrations increased across gestation and were significantly higher than neonatal OPG concentrations. Maternal and neonatal OPG concentrations were not associated with markers of bone turnover or placental OPG expression, but neonatal OPG was inversely associated with neonatal anthropometric measures. Additional research is needed to identify roles of OPG during pregnancy. PMID- 25141265 TI - Novel thromboxane A2 analog-induced IUGR mouse model. AB - Rodents, particularly rats, are used in the majority of intrauterine growth restriction (IUGR) research. An important tool that is lacking in this field is the ability to impose IUGR on transgenic mice. We therefore developed a novel mouse model of chronic IUGR using U-46619, a thromboxane A2 (TXA2) analog, infusion. TXA2 overproduction is prevalent in human pregnancies complicated by cigarette smoking, diabetes mellitus and preeclampsia. In this model, U-46619 micro-osmotic pump infusion in the last week of C57BL/6J mouse gestation caused maternal hypertension. IUGR pups weighed 15% less, had lighter brain, lung, liver and kidney weights, but had similar nose-to-anus lengths compared with sham pups at birth. Metabolically, IUGR pups showed increased essential branched-chain amino acids. They were normoglycemic yet hypoinsulinemic. They showed decreased hepatic mRNA levels of total insulin-like growth factor-1 and its variants, but increased level of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha. IUGR offspring were growth restricted from birth (P1) through postnatal day 21 (P21). IUGR males caught up with sham males in weight by P28, whereas IUGR females caught up with sham females by P77. IUGR males surpassed sham males in weight by P238. In summary, we have a non-brain sparing IUGR mouse model that has a relative ease of surgical IUGR induction and exhibits features similar to the chronic IUGR offspring of humans and other animal models. As transgenic technology predominates in mice, this model now permits the imposition of IUGR on transgenic mice to interrogate mechanisms of fetal origins of adult disease. PMID- 25141266 TI - The effect of high multivitamin diet during pregnancy on food intake and glucose metabolism in Wistar rat offspring fed low-vitamin diets post weaning. AB - Rat offspring born to dams fed a high multivitamin diet (HV) are shown to have increased risks of obesity and metabolic syndrome. We hypothesized that a low vitamin postweaning diet would enhance these characteristics in offspring born to HV dams. During pregnancy, Wistar rats were fed the AIN-93G diet with or without a 10-fold increase in vitamin content. In Experiment 1, at weaning, males were fed the recommended diet (RV) or a diet with 1/3 the vitamin content (1/3 RV) for 12 weeks. In Experiment 2, males and females were fed the RV diet or 1/6 RV diet for 35 weeks. Body weight was measured on a weekly basis, food intake on a daily basis, and for 1 h after an overnight fast following glucose gavage at 6, 12 and 24 weeks. Blood glucose and insulin responses to an oral glucose load were measured at 30 weeks. Males from HV dams, compared with those from RV dams, gained more weight in Experiment 1 (+7%, P < 0.05) and Experiment 2 (+11%, P < 0.0001), along with higher glucose response (+33%, P < 0.05). The 1/6 RV pup diet led to lower weight gain in males (-16%, P < 0.0001) and females (-13%, P < 0.0005), and lower food intake in males (-9%, P < 0.01) independent of the gestational diet. Females on the 1/6 RV diet and from HV dams had higher 1 h food intake (+36%, P < 0.05) and lower insulin response (-25%, P < 0.05) compared with those from RV dams. Exposure of the offspring to low-vitamin diets did not amplify the expression of the metabolic syndrome observed in those born to dams fed an HV diet. PMID- 25141267 TI - Thermoelectric Seebeck effect in oxide-based resistive switching memory. AB - Reversible resistive switching induced by an electric field in oxide-based resistive switching memory shows a promising application in future information storage and processing. It is believed that there are some local conductive filaments formed and ruptured in the resistive switching process. However, as a fundamental question, how electron transports in the formed conductive filament is still under debate due to the difficulty to directly characterize its physical and electrical properties. Here we investigate the intrinsic electronic transport mechanism in such conductive filament by measuring thermoelectric Seebeck effects. We show that the small-polaron hopping model can well describe the electronic transport process for all resistance states, although the corresponding temperature-dependent resistance behaviours are contrary. Moreover, at low resistance states, we observe a clear semiconductor-metal transition around 150 K. These results provide insight in understanding resistive switching process and establish a basic framework for modelling resistive switching behaviour. PMID- 25141268 TI - Contrasting reactivity behaviour of the [RuHCl(CO)(PNP)] complex with electrophilic reagents XOTf (X = H, CH3, Me3Si). AB - A new ruthenium pincer complex [RuHCl(CO)(PNP)] (PNP = PhCH2N(CH2CH2PPh2)2) () was synthesized and characterized. The reactivity of complex with electrophilic reagents XOTf (X = H, CH3, and Me3Si; OTf = CF3SO3) was studied by variable temperature NMR spectroscopy with an aim to observe and characterize sigma complexes of type [Ru(eta(2)-HX)Cl(CO)(PNP)][OTf] (X = H (), CH3 (), Me3Si ()). Reaction of complex with HOTf resulted in the formation of the dihydrogen complex, [Ru(eta(2)-H2)Cl(CO)(PNP)[OTf] (). On the other hand, the reaction between complex and MeOTf and Me3SiOTf resulted in the direct elimination of MeCl and Me3SiCl via a SN2 type of reaction without the intermediacy of the respective sigma complexes and . This contrasting reactivity behaviour has been rationalized taking into consideration the approach of the relatively bulky electrophiles CH3(+) and Me3Si(+) onto the hydride moiety of the ruthenium fragment, which is sterically hindered. PMID- 25141269 TI - A highly responsive and selective fluorescent probe for imaging physiological hydrogen sulfide. AB - The discovery of hydrogen sulfide (H2S) as a novel gasotransmitter for cell signaling and other pathophysiological processes has spurred tremendous interest in developing analytical methods for its detection in biological systems. Herein, we report the development of a highly responsive and selective genetically encoded H2S probe, hsGFP, for the detection of H2S both in vitro and in living mammalian cells. hsGFP bestows a combination of favorable properties, including large fluorescence responses, high efficiency in folding and chromophore formation, and excellent sensitivity and selectivity toward H2S. As a genetically encoded probe, hsGFP can be readily and precisely localized to subcellular domains such as mitochondria, cell nuclei, and ion channels. hsGFP was further utilized to image H2S enzymatically produced from l-cysteine in human embryonic kidney (HEK) 293T cells. PMID- 25141270 TI - A semipermeable enzymatic nanoreactor as an efficient modulator for reversible pH regulation. AB - Here we propose a new concept for the fabrication of a semipermeable enzymatic nanoreactor as an efficient modulator to reversibly switch the pH of an aqueous environment. We used amino-functionalized, expanded mesoporous silica nanoparticles (EMSN) as a model nanocarrier to load enzymes. In order to protect enzymes from the interference of a complicated environment, polyelectrolyte multilayers (PEMs) were coated on the surface of the EMSN through layer by layer (LbL) assembly. These PEMs can serve as semipermeable membranes, allowing small molecules to diffuse in and out freely while trapping the enzymes in the nanoreactors. Compared with traditional electrochemical stimulation or optical control methods, our enzymatic regulation platform is easy to operate without complicated instruments. In addition, this system can cover a wide range of pH values and conveniently regulate pH values by simply controlling the concentrations of catalysts or reactants. Meanwhile, this strategy could be generalized to other enzymes or nanocarriers to achieve reversible pH regulation for different purposes. The switched pH values can be implemented for the modulation of the conformational changes of nucleic acids and activation of the charge conversion in drug delivery applications. PMID- 25141271 TI - Activation of avian aryl hydrocarbon receptor and inter-species sensitivity variations by polychlorinated diphenylsulfides. AB - It was hypothesized that polychlorinated diphenyl sulfides (PCDPSs) can potentially interact with an aryl hydrocarbon receptor (AHR) and thereby cause adverse effects in wildlife like birds. A recently developed avian AHR1 luciferase report gene (LRG) assay was used to assess the interaction between avian AHR1 and 18 PCDPSs and to compare the interspecies sensitivity among chicken, ring-necked pheasant, and Japanese quail by PCDPSs. Most of the tested PCDPSs could activate the AHR1-mediated pathways in avian species, and the relative potency (ReP) of the PCDPSs increased with the increasing number of substituted Cl atoms. The rank orders of PCDPSs potency were generally similar among birds, although the ReP varied. In addition, not all the sensitivity rank orders of avian AHR1 constructs for PCDPSs were consistent with that of TCDD. ReP values of PCDPSs suggested that some PCDPSs like 2,3,3',4,5,6-hexa-CDPS and 2,2',3,3',4,5,6-hepta-CDPS are higher than the avian WHO-TEFs of OctaCDD, OctaCDF, and most of the coplanar PCBs. Our results report for the first time the activation of an AHR1-mediated molecular toxicological mechanism by PCDPSs, and provide the ranking of ReP and relative sensitivity values of different congeners, which could guide the further toxicity test of this group of potential high priority environmental pollutants. PMID- 25141272 TI - Allostatic load and the assessment of cumulative biological risk in biobehavioral medicine: challenges and opportunities. AB - Allostatic load provides a useful framework for conceptualizing the multisystem physiological impact of sustained stress and its effects on health and well being. Research across two decades shows that allostatic load indices predict health outcomes including all-cause mortality and vary with stress and related psychosocial constructs. The study by Slopen and colleagues in this issue provides an example both of the utility of the allostatic load framework and of limitations in related literature, such as inconsistencies in conceptualization and measurement across studies, and the frequent application of cross-sectional designs. The current article describes these limitations and provides suggestions for further research to enhance the value and utility of the allostatic load framework in biobehavioral medicine research. PMID- 25141273 TI - Risk of bias in trial-based economic evaluations: identification of sources and bias-reducing strategies. AB - OBJECTIVE: The objectives of this article are first to give an overview of the risks of bias in trial-based economic evaluations and, second, to identify how key sources for bias can be revealed and overcome (i.e. what bias-reducing strategies might be employed) in future trial-based economic evaluations in the field of health psychology. DESIGN: Narrative review discussing sources of bias in trial-based economic evaluations and bias-reducing strategies. RESULTS: We identified 11 biases and assigned them to a particular trial phase. A distinction is made between pre-trial biases, biases during the trial and biases that are relevant after the actual trial. All potential forms of bias are discussed in detail and strategies are shown to detect and overcome these biases. CONCLUSION: In order to avoid bias in trial-based economic evaluations, one has to be aware of all the possible forms of bias. All stakeholders have to examine trial-based economic evaluations in a rigorous and stringent manner. This article can be helpful in this examination as it gives an overview of the possible biases which researchers should take into account. PMID- 25141274 TI - High-intensity focused ultrasound ablation: an effective and safe treatment for secondary hypersplenism. AB - OBJECTIVE: Hypersplenism is a common disease. The conventional treatment is splenectomy and partial splenic embolization; however, both of them have high complication rates and technical defects. Therefore, safer and more effective techniques should be considered for the treatment of hypersplenism. High intensity focused ultrasound (HIFU) may provide an effective and safe way for treatment of hypersplenism. Therefore, we conducted this study to assess the safety and efficacy of HIFU in treatment of secondary hypersplenism. METHODS: A total of 28 patients who suffered from secondary hypersplenism were treated with HIFU ablation. All patients who underwent HIFU were closely followed-up over a year. MRI scan was performed, and the spleens were observed. Blood counts and liver function tests were also carried out. RESULTS: In the follow-up process, the levels of white blood cells and platelets in the blood after HIFU were significantly higher than those before HIFU, liver function also improved after HIFU treatment. In addition, the symptoms were ameliorated significantly or even disappeared. The MRI showed that the ablation area had turned into a non-perfused volume, and after 12 months of HIFU ablation, the ablated area shrank evidently; the sunken spleen formed a lobulated shape and the splenic volume decreased. CONCLUSION: HIFU ablation is a safe, effective and non-invasive approach for secondary hypersplenism. ADVANCES IN KNOWLEDGE: For the first time we used HIFU ablation to treat secondary hypersplenism. It not only expands indications of HIFU but also provides better choice for the treatment of secondary hypersplenism. PMID- 25141275 TI - Polymerase chain reaction for the amplification of the 121-bp repetitive sequence of Schistosoma mansoni: a highly sensitive potential diagnostic tool for areas of low endemicity. AB - Schistosomiasis is a disease caused by parasitic flatworms of the genus Schistosoma, whose diagnosis has limitations, such as the low sensitivity and specificity of parasitological and immunological methods, respectively. In the present study an alternative molecular technique requiring previous standardization was carried out using the polymerase chain reaction (PCR) for the amplification of a 121-bp highly repetitive sequence for Schistosoma mansoni. DNA was extracted from eggs of S. mansoni by salting out. Different conditions were standardized for the PCR technique, including the concentration of reagents and the DNA template, annealing temperature and number of cycles, followed by the determination of the analytical sensitivity and specificity of the technique. Furthermore, the standardized PCR technique was employed in DNA extracted, using Chelex(r)100, from samples of sera of patients with an immunodiagnosis of schistosomiasis. The optimal conditions for the PCR were 2.5 mm MgCl2, 150 mm deoxynucleoside triphosphates (dNTPs), 0.4 MUm primers, 0.75 U DNA polymerase, using 35 cycles and an annealing temperature of 63 degrees C. The analytical sensitivity of the PCR was 10 attograms of DNA and the specificity was 100%. The DNA sequence was successfully detected in the sera of two patients, demonstrating schistosomiasis transmission, although low, in the community studied. The standardized PCR technique, using smaller amounts of reagents than in the original protocol, is highly sensitive and specific for the detection of DNA from S. mansoni and could be an important tool for diagnosis in areas of low endemicity. PMID- 25141276 TI - Relationship of preexisting influenza hemagglutination inhibition, complement dependent lytic, and antibody-dependent cellular cytotoxicity antibodies to the development of clinical illness in a prospective study of A(H1N1)pdm09 Influenza in children. AB - The hemagglutination inhibition (HAI) antibody titer is considered the primary immune correlate of protection for influenza. However, recent studies have highlighted the limitations on the use of the HAI titer as a correlate in at-risk populations such as children and older adults. In addition to the neutralization of cell-free virus by antibodies to hemagglutinin and interference of virus release from infected cells by antibodies to neuraminidase, influenza virus specific antibodies specifically can bind to infected cells and lyse virus infected cells through the activation of complement or natural killer (NK) cells, via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent lysis (CDL). We evaluated preexisting HAI, CDL, and ADCC antibodies in young children enrolled in a prospective cohort study of dengue during the epidemic with influenza A(H1N1)pdm09 virus to determine associations between preexisting antibodies and the occurrence of clinical or subclinical influenza virus infection. Though both preexisting HAI and CDL antibodies were associated with protection against clinical influenza, our data suggested that CDL was not a better correlate than HAI. We found that ADCC antibodies behaved differently from HAI and CDL antibodies. Unlike HAI and CDL antibodies, preexisting ADCC antibodies did not correlate with protection against clinical influenza. In fact, ADCC antibodies were detected more frequently in the clinical influenza group than the subclinical group. In addition, in contrast to HAI and CDL antibodies, HAI and the ADCC antibodies titers did not correlate. We also found that ADCC, but not CDL or HAI antibodies, positively correlated with the ages of the children. PMID- 25141277 TI - Target repression induced by endogenous microRNAs: large differences, small effects. AB - MicroRNAs are small RNAs that regulate protein levels. It is commonly assumed that the expression level of a microRNA is directly correlated with its repressive activity - that is, highly expressed microRNAs will repress their target mRNAs more. Here we investigate the quantitative relationship between endogenous microRNA expression and repression for 32 mature microRNAs in Drosophila melanogaster S2 cells. In general, we find that more abundant microRNAs repress their targets to a greater degree. However, the relationship between expression and repression is nonlinear, such that a 10-fold greater microRNA concentration produces only a 10% increase in target repression. The expression/repression relationship is the same for both dominant guide microRNAs and minor mature products (so-called passenger strands/microRNA* sequences). However, we find examples of microRNAs whose cellular concentrations differ by several orders of magnitude, yet induce similar repression of target mRNAs. Likewise, microRNAs with similar expression can have very different repressive abilities. We show that the association of microRNAs with Argonaute proteins does not explain this variation in repression. The observed relationship is consistent with the limiting step in target repression being the association of the microRNA/RISC complex with the target site. These findings argue that modest changes in cellular microRNA concentration will have minor effects on repression of targets. PMID- 25141278 TI - Virus-mediated chemical changes in rice plants impact the relationship between non-vector planthopper Nilaparvata lugens Stal and its egg parasitoid Anagrus nilaparvatae Pang et Wang. AB - In order to clarify the impacts of southern rice black-streaked dwarf virus (SRBSDV) infection on rice plants, rice planthoppers and natural enemies, differences in nutrients and volatile secondary metabolites between infected and healthy rice plants were examined. Furthermore, the impacts of virus-mediated changes in plants on the population growth of non-vector brown planthopper (BPH), Nilaparvata lugens, and the selectivity and parasitic capability of planthopper egg parasitoid Anagrus nilaparvatae were studied. The results showed that rice plants had no significant changes in amino acid and soluble sugar contents after SRBSDV infection, and SRBSDV-infected plants had no significant effect on population growth of non-vector BPH. A. nilaparvatae preferred BPH eggs both in infected and healthy rice plants, and tended to parasitize eggs on infected plants, but it had no significant preference for infected plants or healthy plants. GC-MS analysis showed that tridecylic aldehyde occurred only in rice plants infected with SRBSDV, whereas octanal, undecane, methyl salicylate and hexadecane occurred only in healthy rice plants. However, in tests of behavioral responses to these five volatile substances using a Y-tube olfactometer, A. nilaparvatae did not show obvious selectivity between single volatile substances at different concentrations and liquid paraffin in the control group. The parasitic capability of A. nilaparvatae did not differ between SRBSDV-infected plants and healthy plant seedlings. The results suggested that SRBSDV-infected plants have no significant impacts on the non-vector planthopper and its egg parasitoid, A. nilaparvatae. PMID- 25141279 TI - Molecular and morphological evidence reveals a new species in the Phyllomedusa hypochondrialis group (Hylidae, Phyllomedusinae) from the Atlantic Forest of the highlands of southern Brazil. AB - The taxonomic status of a disjunctive population of Phyllomedusa from southern Brazil was diagnosed using molecular, chromosomal, and morphological approaches, which resulted in the recognition of a new species of the P. hypochondrialis group. Here, we describe P. rustica sp. n. from the Atlantic Forest biome, found in natural highland grassland formations on a plateau in the south of Brazil. Phylogenetic inferences placed P. rustica sp. n. in a subclade that includes P. rhodei + all the highland species of the clade. Chromosomal morphology is conservative, supporting the inference of homologies among the karyotypes of the species of this genus. Phyllomedusa rustica is apparently restricted to its type locality, and we discuss the potential impact on the strategies applied to the conservation of the natural grassland formations found within the Brazilian Atlantic Forest biome in southern Brazil. We suggest that conservation strategies should be modified to guarantee the preservation of this species. PMID- 25141280 TI - Antimicrobial and mechanical properties of beta-cyclodextrin inclusion with essential oils in chitosan films. AB - Chitosan films incorporated with various concentrations of the complex of beta cyclodextrin and essential oils (beta-CD/EO) were prepared and investigated for antimicrobial, mechanical, and physical properties. Four bacterial strains that commonly contaminate food products were chosen as target bacteria to evaluate the antimicrobial activity of the prepared films. The incorporation of beta-CD/EO significantly increased the antimicrobial activities of the chitosan films against Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Listeria monocytogenes. It was also found that tensile strength (TS) of chitosan film was significantly increased with the incorporation of the beta-cyclodextrin and 0.75% essential oils complex. The elongation at break (EB) decreased with the increasing concentrations of essential oils. Inclusion of the complex of beta cyclodextrin and 0.25% essential oils also significantly decreased water vapor permeability (WVP) of chitosan films. Our results suggest that chitosan films containing beta-CD/EO could be used as active food-packaging material. PMID- 25141281 TI - Is imidacloprid an effective alternative for controlling pyrethroid-resistant populations of Triatoma infestans (Hemiptera: Reduviidae) in the Gran Chaco ecoregion? AB - The prevention of Chagas disease is based primarily on the chemical control of Triatoma infestans (Klug) using pyrethroid insecticides. However, high resistance levels, correlated with control failures, have been detected in Argentina and Bolivia. A previous study at our laboratory found that imidacloprid could serve as an alternative to pyrethroid insecticides. We studied the delayed toxicity of imidacloprid and the influence of the blood feeding condition of the insect on the toxicity of this insecticide; we also studied the effectiveness of various commercial imidacloprid formulations against a pyrethroid-resistant T. infestans population from the Gran Chaco ecoregion. Variations in the toxic effects of imidacloprid were not observed up to 72 h after exposure and were not found to depend on the blood feeding condition of susceptible and resistant individuals. Of the three different studied formulations of imidacloprid on glass and filter paper, only the spot-on formulation was effective. This formulation was applied to pigeons at doses of 1, 5, 20 and 40 mg/bird. The nymphs that fed on pigeons treated with 20 mg or 40 mg of the formulation showed a higher mortality rate than the control group one day and seven days post-treatment (p < 0.01). A spot on formulation of imidacloprid was effective against pyrethroid-resistant T. infestans populations at the laboratory level. PMID- 25141282 TI - G6PD deficiency in Latin America: systematic review on prevalence and variants. AB - Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curacao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available. PMID- 25141284 TI - Molecular detection of Mayaro virus during a dengue outbreak in the state of Mato Grosso, Central-West Brazil. AB - Mayaro virus (MAYV) is frequently reported in Pan-Amazonia. The aim of this study was to investigate the circulation of alphaviruses during a dengue outbreak in the state of Mato Grosso, Brazil. Serum samples from dengue-suspected patients were subjected to multiplex semi-nested reverse transcriptase polymerase chain reaction for 11 flaviviruses and five alphaviruses, to nucleotide sequencing and to viral isolation. MAYV was detected in 15 (2.5%) of 604 patients. Twelve were co-infected with dengue virus 4, which was isolated from 10 patients. The molecular detection of MAYV in dengue-suspected patients suggests that other arboviruses may be silently circulating during dengue outbreaks in Brazil. PMID- 25141283 TI - Influence of age on the haemoglobin concentration of malaria-infected patients in a reference centre in the Brazilian Amazon. AB - Anaemia is amongst the major complications of malaria, a major public health problem in the Amazon Region in Latin America. We examined the haemoglobin (Hb) concentrations of malaria-infected patients and compared it to that of malaria negative febrile patients and afebrile controls. The haematological parameters of febrile patients who had a thick-blood-smear performed at an infectious diseases reference centre of the Brazilian Amazon between December 2009-January 2012 were retrieved together with clinical data. An afebrile community control group was composed from a survey performed in a malaria-endemic area. Hb concentrations and anaemia prevalence were analysed according to clinical-epidemiological status and demographic characteristics. In total, 7,831 observations were included. Patients with Plasmodium falciparum infection had lower mean Hb concentrations (10.5 g/dL) followed by P. vivax-infected individuals (12.4 g/dL), community controls (12.8 g/dL) and malaria-negative febrile patients (13.1 g/dL) (p < 0.001). Age, gender and clinical-epidemiological status were strong independent predictors for both outcomes. Amongst malaria-infected individuals, women in the reproductive age had considerably lower Hb concentrations. In this moderate transmission intensity setting, both vivax and falciparum malaria are associated with reduced Hb concentrations and risk of anaemia throughout a wide age range. PMID- 25141285 TI - Anopheles gambiae eicosanoids modulate Plasmodium berghei survival from oocyst to salivary gland invasion. AB - Eicosanoids affect the immunity of several pathogen/insect models, but their role on the Anopheles gambiae response to Plasmodium is still unknown. Plasmodium berghei-infected mosquitoes were injected with an eicosanoid biosynthesis inhibitor, indomethacin (IN), or a substrate, arachidonic acid (AA), at day 7 or day 12 post-infection (p.i.). Salivary gland invasion was evaluated by sporozoite counts at day 21 p.i. IN promoted infection upon sporozoite release from oocysts, but inhibited infection when sporozoites were still maturing within the oocysts, as observed by a reduction in the number of sporozoites reaching the salivary glands. AA treatment had the opposite effect. We show for the first time that An. gambiae can modulate parasite survival through eicosanoids by exerting an antagonistic or agonistic effect on the parasite, depending on its stage of development. PMID- 25141286 TI - The copper(I)-catalyzed tandem reaction of o-alkynylphenyl isothiocyanates with isocyanides: a rapid synthesis of 5H-benzo[d]imidazo[5,1-b][1,3]thiazines. AB - An efficient route to 5H-benzo[d]imidazo[5,1-b][1,3]thiazines has been developed using the copper(i)-catalyzed tandem reaction of o-alkynylphenyl isothiocyanates with isocyanides in THF with Cs2CO3 as base. The present tandem process allows the assembly of a variety of 5H-benzo[d]imidazo[5,1-b][1,3]thiazines in good to excellent yields. PMID- 25141288 TI - Generation and Evaluation of a Genome-Scale Metabolic Network Model of Synechococcus elongatus PCC7942. AB - The reconstruction of genome-scale metabolic models and their applications represent a great advantage of systems biology. Through their use as metabolic flux simulation models, production of industrially-interesting metabolites can be predicted. Due to the growing number of studies of metabolic models driven by the increasing genomic sequencing projects, it is important to conceptualize steps of reconstruction and analysis. We have focused our work in the cyanobacterium Synechococcus elongatus PCC7942, for which several analyses and insights are unveiled. A comprehensive approach has been used, which can be of interest to lead the process of manual curation and genome-scale metabolic analysis. The final model, iSyf715 includes 851 reactions and 838 metabolites. A biomass equation, which encompasses elementary building blocks to allow cell growth, is also included. The applicability of the model is finally demonstrated by simulating autotrophic growth conditions of Synechococcus elongatus PCC7942. PMID- 25141290 TI - Protocol of surgical indications for scar contracture release before childbirth: women with severe abdominal scars after burn injuries. AB - It is difficult to determine if women with severe abdominal burn scar contractures can have uneventful pregnancies and births. There are few reports involving the relationship between severe abdominal scar contractures and pregnancy/childbirth. Furthermore, all of these reports are based on retrospective studies. The present study focused on women with severe abdominal burn scar contractures with desired fertility. This study investigated whether or not normal childbirth is possible, the necessity of scar contracture release, and the delivery method. In addition, a protocol developed by this hospital was prospectively evaluated. Surgery was indicated in women with scars covering >=75% of the total abdominal area. The scarred area in the upper abdomen, superior to the navel, was considered particularly important. The protocol of this study serves merely as a reference, and future studies are needed with an increased number of cases. PMID- 25141289 TI - Do patients' symptoms and interpersonal problems improve in psychotherapeutic hospital treatment in Germany? A systematic review and meta-analysis. AB - BACKGROUND: In Germany, inpatient psychotherapy plays a unique role in the treatment of patients with common mental disorders of higher severity. In addition to psychiatric inpatient services, psychotherapeutic hospital treatment and psychosomatic rehabilitation are offered as independent inpatient treatment options. This meta-analysis aims to provide systematic evidence for psychotherapeutic hospital treatment in Germany regarding its effects on symptomatic and interpersonal impairment. METHODOLOGY: Relevant papers were identified by electronic database search and hand search. Randomized controlled trials as well as naturalistic prospective studies (including post-therapy and follow-up assessments) evaluating psychotherapeutic hospital treatment of mentally ill adults in Germany were included. Outcomes were required to be quantified by either the Symptom-Checklist (SCL-90-R or short versions) or the Inventory of Interpersonal Problems (IIP-64 or short versions). Effect sizes (Hedges' g) were combined using random effect models. PRINCIPAL FINDINGS: Sixty seven papers representing 59 studies fulfilled inclusion criteria. Meta-analysis yielded a medium within-group effect size for symptom change at discharge (g = 0.72; 95% CI 0.68-0.76), with a small reduction to follow-up (g = 0.61; 95% CI 0.55-0.68). Regarding interpersonal problems, a small effect size was found at discharge (g = 0.35; 95% CI 0.29-0.41), which increased to follow-up (g = 0.48; 95% CI 0.36-0.60). While higher impairment at intake was associated with a larger effect size in both measures, longer treatment duration was related to lower effect sizes in SCL GSI and to larger effect sizes in IIP Total. CONCLUSIONS: Psychotherapeutic hospital treatment may be considered an effective treatment. In accordance with Howard's phase model of psychotherapy outcome, the present study demonstrated that symptom distress changes more quickly and strongly than interpersonal problems. Preliminary analyses show impairment at intake and treatment duration to be the strongest outcome predictors. Further analyses regarding this relationship are required. PMID- 25141291 TI - Shining new light on the multifaceted dissociative photoionisation dynamics of CCl4. AB - Internal energy selected carbon tetrachloride cations have been prepared by imaging photoelectron photoion coincidence (iPEPICO) spectroscopy using synchrotron vacuum ultraviolet radiation. The threshold photoelectron spectrum shows a newly observed vibrational progression corresponding to the nu2(e) scissors mode of CCl4(+) in the third, B(2)E band. Ab initio results on the first four doublet and lowest-lying quartet electronic states along the Cl3C(+)-Cl dissociation coordinate show the B state to be strongly bound, and support its relative longevity. The X(2)T1 and A(2)T2 cationic states, on the other hand, are barely bound and dissociate promptly. The C(2)T2 state may intersystem cross to the quartet a state, which dissociates to a triplet state of the CCl3(+) fragment ion. This path is unique among analogous MX4(+) (M = C, Si, Ge; X = F, Cl, Br) systems, among which several have been shown to have long-lived C states, which decay by fluorescence. The breakdown diagram, recorded here for the first time for the complete valence photoionisation energy range of CCl4, is interpreted in the context of literature based and CBS-QB3, G4, and W1U computed dissociative photoionisation energies. No Cl2-loss channel is observed in association with the CCl2(+) or CCl(+) fragments below the 2 or 3 Cl-loss reaction energies, and Cl2 loss is unlikely to be a major channel above them. The breakdown diagram is modelled based on the calculated dissociative photoionisation onsets and assuming a statistical redistribution of the excess energy. The model indicates that dissociation is not impulsive at higher energies, and confirms that the C(2)T2 state of CCl4(+) forms triplet-state CCl3(+) fragments with some of the excess energy trapped as electronic excitation energy in CCl3(+). PMID- 25141292 TI - Chemoselective Wittig and Michael ligations of unprotected peptidyl phosphoranes in water furnish potent inhibitors of caspase-3. AB - Unprotected peptidyl phosphoranes 1 with sequence Ac-L-aspartyl-L-glutamyl-L valinyl-L-aspartyl are released from polymer support and react with aliphatic and aromatic aldehydes in aqueous medium in a Wittig ligation. Obtained vinyl ketones 6-12 are potent inhibitors of caspase-3. Vinyl ketone 6, derived from formaldehyde, undergoes Michael ligations with thiol nucleophiles furnishing products 14-16, also in aqueous medium. The demonstrated ligation reactions enable the modification of complex functionalized peptides in water providing bioactive protein ligands without side-chain protection. PMID- 25141293 TI - Seasonal variation and hypertensive disorders of pregnancy in eastern Sudan. AB - The aim of this study was to investigate the seasonal variation and hypertensive disorders of pregnancy in eastern Sudan, in the period between January 2008 and December 2010. The medical files of women attending at Kassala hospital, eastern Sudan with hypertension, with or without proteinuria were retrospectively retrieved. The data of patients with hypertensive disorders of pregnancy were compared with a similar number of controls that were normotensive and non proteinuric. During the study period, there were 9,578 deliveries; 153 patients had hypertensive disorders of pregnancy, yielding an incidence rate of 1.6%. Of all cases and controls (306), there were 183 (59.8%) deliveries in winter, 84 (27.5%) in summer and 39 (12.7%) in autumn. The highest rate of pre-eclampsia was in winter (1.1%) (CI = 1.1-2.7, OR = 1.7, p = 0.004) and the lowest rate was in autumn (0.2%) (CI = 0.4-1.8, OR = 0.8, p = 0.758.). Our study revealed significant association between the incidence of hypertensive disorders of pregnancy and the winter season (103 (67.3%) vs 80 (52.3%), p = 0.001). Thus, more attention in the winter season might reduce the morbidity and mortality of hypertensive disorders of pregnancy. PMID- 25141294 TI - Cryogenic electron microscopy study of nanoemulsion formation from microemulsions. AB - We examine a process of preparing oil-in-water nanoemulsions by quenching (diluting and cooling) precursor microemulsions made with nonionic surfactants and a cosurfactant. The precursor microemulsion structure is varied by changing the concentration of the cosurfactant. Water-continuous microemulsions produce initial nanoemulsion structures that are small and simple, mostly unilamellar vesicles, but microemulsions that are not water-continuous produce initial nanoemulsion structures that are larger and multilamellar. Examination of these structures by cryo-electron microscopy supports the hypothesis that they are initially vesicular structures formed via lamellar intermediate structures, and that if the lamellar structures are too well ordered they fail to produce small simple structures. PMID- 25141295 TI - Comment on "Hydration and mobility of trehalose in aqueous solution". PMID- 25141296 TI - Rapid, selective, and sensitive fluorometric detection of cyanide anions in aqueous media by cyanine dyes with indolium-coumarin linkages. AB - Cyanine dyes with indolium-coumarin linkages exhibit selective fluorescence enhancement for cyanide anions (CN(-)) via the nucleophilic interaction of CN(-) with their indolium carbon atoms. This facilitates rapid (detection time: 1 min) and sensitive (detection limit: 0.4 MUM) sensing of CN(-) in aqueous media. PMID- 25141299 TI - Pulsed laser-deposited MoS2 thin films on W and Si: field emission and photoresponse studies. AB - We report field electron emission investigations on pulsed laser-deposited molybdenum disulfide (MoS2) thin films on W-tip and Si substrates. In both cases, under the chosen growth conditions, the dry process of pulsed laser deposition (PLD) is seen to render a dense nanostructured morphology of MoS2, which is important for local electric field enhancement in field emission application. In the case of the MoS2 film on silicon (Si), the turn-on field required to draw an emission current density of 10 MUA/cm(2) is found to be 2.8 V/MUm. Interestingly, the MoS2 film on a tungsten (W) tip emitter delivers a large emission current density of ~30 mA/cm(2) at a relatively lower applied voltage of ~3.8 kV. Thus, the PLD-MoS2 can be utilized for various field emission-based applications. We also report our results of photodiode-like behavior in (n- and p- type) Si/PLD MoS2 heterostructures. Finally we show that MoS2 films deposited on flexible kapton substrate show a good photoresponse and recovery. Our investigations thus hold great promise for the development of PLD MoS2 films in application domains such as field emitters and heterostructures for novel nanoelectronic devices. PMID- 25141298 TI - Predicting progression of Alzheimer's disease using ordinal regression. AB - We propose a novel approach to predicting disease progression in Alzheimer's disease (AD)--multivariate ordinal regression--which inherently models the ordered nature of brain atrophy spanning normal aging (CTL) to mild cognitive impairment (MCI) to AD. Ordinal regression provides probabilistic class predictions as well as a continuous index of disease progression--the ORCHID (Ordinal Regression Characteristic Index of Dementia) score. We applied ordinal regression to 1023 baseline structural MRI scans from two studies: the US-based Alzheimer's Disease Neuroimaging Initiative (ADNI) and the European based AddNeuroMed program. Here, the acquired AddNeuroMed dataset was used as a completely independent test set for the ordinal regression model trained on the ADNI cohort providing an optimal assessment of model generalizability. Distinguishing CTL-like (CTL and stable MCI) from AD-like (MCI converters and AD) resulted in balanced accuracies of 82% (cross-validation) for ADNI and 79% (independent test set) for AddNeuroMed. For prediction of conversion from MCI to AD, balanced accuracies of 70% (AUC of 0.75) and 75% (AUC of 0.81) were achieved. The ORCHID score was computed for all subjects. We showed that this measure significantly correlated with MMSE at 12 months (rho = -0.64, ADNI and rho = 0.59, AddNeuroMed). Additionally, the ORCHID score can help fractionate subjects with unstable diagnoses (e.g. reverters and healthy controls who later progressed to MCI), moderately late converters (12-24 months) and late converters (24-36 months). A comparison with results in the literature and direct comparison with a binary classifier suggests that the performance of this framework is highly competitive. PMID- 25141300 TI - Role of hydrogen plasma pretreatment in improving passivation of the silicon surface for solar cells applications. AB - We have investigated the role of hydrogen plasma pretreatment in promoting silicon surface passivation, in particular examining its effects on modifying the microstructure of the subsequently deposited thin hydrogenated amorphous silicon (a-Si:H) passivation film. We demonstrate that pretreating the silicon surface with hydrogen plasma for 40 s improves the homogeneity and compactness of the a Si:H film by enhancing precursor diffusion and thus increasing the minority carrier lifetime (tau(eff)). However, excessive pretreatment also increases the density of dangling bond defects on the surface due to etching effects of the hydrogen plasma. By varying the duration of hydrogen plasma pretreatment in fabricating silicon heterojunction solar cells based on textured substrates, we also demonstrate that, although the performance of the solar cells shows a similar tendency to that of the tau(eff) on polished wafers, the optimal duration is prolonged owing to the differences in the surface morphology of the substrates. These results suggest that the hydrogen plasma condition must be carefully regulated to achieve the optimal level of surface atomic hydrogen coverage and avoid the generation of defects on the silicon wafer. PMID- 25141301 TI - Lamniform shark teeth from the late cretaceous of southernmost South America (Santa Cruz province, Argentina). AB - Here we report multiple lamniform shark teeth recovered from fluvial sediments in the (Campanian-Maastrichtian) Cerro Fortaleza Formation, Santa Cruz Province, Argentina. This small tooth assemblage is compared to various lamniform sharks possessing similar dental morphologies, including Archaeolamna, Cretalamna, Dwardius, Dallasiella, and Cretodus. Although the teeth share numerous morphological features with the genus Archaeolamna, including a developed neck that maintains a relatively consistent width along the base of the crown, the small sample size and incomplete nature of these specimens precludes definitive taxonomic assignment. Regardless, the discovery of selachian teeth unique from those previously described for the region broadens the known diversity of Late Cretaceous South American sharks. Additionally, the discovery of the teeth in fluvial sandstone may indicate a euryhaline paleobiology in the lamniform taxon or taxa represented by this tooth assemblage. PMID- 25141303 TI - Insurance status is associated with treatment allocation and outcomes after subarachnoid hemorrhage. AB - OBJECTIVE: Subarachnoid hemorrhage (SAH) is a particularly devastating type of stroke which is responsible for one third of all stroke-related years of potential life lost before age 65. Surgical treatment has been shown to decrease both morbidity and mortality after subarachnoid hemorrhage. We hypothesized that payer status other than private insurance is associated with lower allocation to surgical treatment for patients with SAH and worse outcomes. DESIGN: We examined the association between insurance type and surgical treatment allocation and outcomes for patients with SAH while adjusting for a wide range of patient and hospital factors. We analyzed the Nationwide Inpatient Sample hospital discharge database using survey procedures to produce weighted estimates representative of the United States population. PATIENTS: We studied 21047 discharges, representing a weighted estimate of 102595 patients age 18 and above with a discharge diagnosis of SAH between 2003 and 2008. MEASUREMENTS: Multivariable logistic and generalized linear regression analyses were used to assess for any associations between insurance status and surgery allocation and outcomes. MAIN RESULTS: Despite the benefits of surgery 66% of SAH patients did not undergo surgical treatment to prevent rebleeding. Mortality was more than twice as likely for patients with no surgical treatment compared to those who received surgery. Medicare patients were significantly less likely to receive surgical treatment. CONCLUSIONS: Nearly two thirds of patients with SAH don't receive operative care, and Medicare patients were significantly less likely to receive surgical treatment than other patients. Bias against the elderly and those with chronic illness and disability may play a part in these findings. A system of regionalized care for patients presenting with SAH may reduce disparities and improve appropriate allocation to surgical care and deserves prospective study. PMID- 25141304 TI - Exploring microRNA-like small RNAs in the filamentous fungus Fusarium oxysporum. AB - RNA silencing such as quelling and meiotic silencing by unpaired DNA (MSUD) and several other classes of special small RNAs have been discovered in filamentous fungi recently. More than four different mechanisms of microRNA-like RNAs (milRNAs) production have been illustrated in the model fungus Neurospora crassa including a dicer-independent pathway. To date, very little work focusing on small RNAs in fungi has been reported and no universal or particular characteristic of milRNAs were defined clearly. In this study, small RNA and degradome libraries were constructed and subsequently deep sequenced for investigating milRNAs and their potential cleavage targets on the genome level in the filamentous fungus F. oxysporum f. sp. lycopersici. As a result, there is no intersection of conserved miRNAs found by BLASTing against the miRBase. Further analysis showed that the small RNA population of F. oxysporum shared many common features with the small RNAs from N. crassa and other fungi. According to the known standards of miRNA prediction in plants and animals, milRNA candidates from 8 families (comprising 19 members) were screened out and identified. However, none of them could trigger target cleavage based on the degradome data. Moreover, most major signals of cleavage in transcripts could not match appropriate complementary small RNAs, suggesting that other predominant modes for milRNA mediated gene regulation could exist in F. oxysporum. In addition, the PAREsnip program was utilized for comprehensive analysis and 3 families of small RNAs leading to transcript cleavage were experimentally validated. Altogether, our findings provided valuable information and important hints for better understanding the functions of the small RNAs and milRNAs in the fungal kingdom. PMID- 25141305 TI - Positive effects of plant genotypic and species diversity on anti-herbivore defenses in a tropical tree species. AB - Despite increasing evidence that plant intra- and inter-specific diversity increases primary productivity, and that such effect may in turn cascade up to influence herbivores, there is little information about plant diversity effects on plant anti-herbivore defenses, the relative importance of different sources of plant diversity, and the mechanisms for such effects. For example, increased plant growth at high diversity may lead to reduced investment in defenses via growth-defense trade-offs. Alternatively, positive effects of plant diversity on plant growth may lead to increased herbivore abundance which in turn leads to a greater investment in plant defenses. The magnitude of trait variation underlying diversity effects is usually greater among species than among genotypes within a given species, so plant species diversity effects on resource use by producers as well as on higher trophic levels should be stronger than genotypic diversity effects. Here we compared the relative importance of plant genotypic and species diversity on anti-herbivore defenses and whether such effects are mediated indirectly via diversity effects on plant growth and/or herbivore damage. To this end, we performed a large-scale field experiment where we manipulated genotypic diversity of big-leaf mahogany (Swietenia macrophylla) and tree species diversity, and measured effects on mahogany growth, damage by the stem-boring specialist caterpillar Hypsipyla grandella, and defensive traits (polyphenolics and condensed tannins in stem and leaves). We found that both forms of plant diversity had positive effects on stem (but not leaf) defenses. However, neither source of diversity influenced mahogany growth, and diversity effects on defenses were not mediated by either growth-defense trade-offs or changes in stem-borer damage. Although the mechanism(s) of diversity effects on plant defenses are yet to be determined, our study is one of the few to test for and show producer diversity effects on plant chemical defenses. PMID- 25141306 TI - Dancing bees improve colony foraging success as long-term benefits outweigh short term costs. AB - Waggle dancing bees provide nestmates with spatial information about high quality resources. Surprisingly, attempts to quantify the benefits of this encoded spatial information have failed to find positive effects on colony foraging success under many ecological circumstances. Experimental designs have often involved measuring the foraging success of colonies that were repeatedly switched between oriented dances versus disoriented dances (i.e. communicating vectors versus not communicating vectors). However, if recruited bees continue to visit profitable food sources for more than one day, this procedure would lead to confounded results because of the long-term effects of successful recruitment events. Using agent-based simulations, we found that spatial information was beneficial in almost all ecological situations. Contrary to common belief, the benefits of recruitment increased with environmental stability because benefits can accumulate over time to outweigh the short-term costs of recruitment. Furthermore, we found that in simulations mimicking previous experiments, the benefits of communication were considerably underestimated (at low food density) or not detected at all (at medium and high densities). Our results suggest that the benefits of waggle dance communication are currently underestimated and that different experimental designs, which account for potential long-term benefits, are needed to measure empirically how spatial information affects colony foraging success. PMID- 25141310 TI - What is gastritis? What is gastropathy? How is it classified? AB - Stomach endoscopic biopsies are made to determine the diagnosis of the illness, its stage, and follow-up after the treatment. It is very significant to collaborate with the clinician while evaluating endoscopic biopsies. Besides the clinical and laboratory information of the patient, the endoscopic appearance of the lesion should be known. The clinician and pathologist should use the same language and the same terminology. Although new classifications have been made to prevent the confusion of terminologies in neoplastic processes recently, most centers around the world have reported non-invasive neoplasias without giving any certain diagnosis by just commenting on it. The clinician should understand what the pathologist wants to say; pathologists should know the approach of the clinician (repetition of the biopsy, endoscopic resection, surgery). There is Helicobacter pylori (HP) in most of the stomach pathologies as the etiologic agent. No matter if the factor is HP or other etiologic agents, the tissue gives similar responses. That is why clinical-endoscopic indications should be taken into consideration, as well as histological indications, and the reports of the endoscopy should be seen. A good clinicopathologic correlation increases the accuracy of the diagnosis. PMID- 25141311 TI - Clinical characteristics and natural history of asymptomatic erosive esophagitis. AB - BACKGROUND/AIMS: This study was designed to investigate risk factors related to asymptomatic erosive esophagitis and the natural history of both endoscopic findings and reflux-related symptoms in subjects with asymptomatic erosive esophagitis. MATERIALS AND METHODS: On a retrospective basis, data were gathered from patients with erosive esophagitis (Los Angeles classification 3A) who had undergone endoscopic follow-up at St. Vincent Hospital. Data from 313 subjects with erosive esophagitis were investigated. RESULTS: Most patients had mild esophagitis (grade A or B, Los Angeles classification); 198 (63.3%) had reflux symptoms, and 115 (36.7%) lacked typical or atypical symptoms. Asymptomatic erosive esophagitis was associated with non-smoking (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.4-3.9) and lower body mass index (body mass index (BMI); OR, 1.5; 95% CI, 1.0-2.4), while 26% of subjects had recurring reflux related symptoms. Younger subjects were more likely to have reflux-related symptoms (p<0.05). CONCLUSION: Non-smoking and lower BMI are associated with asymptomatic reflux esophagitis. Most asymptomatic subjects with erosive esophagitis remained stable and exhibited unchanged endoscopic findings. PMID- 25141312 TI - Usefulness of insulin-like growth factor II mRNA-binding protein 3 (IMP3) as a new marker for the diagnosis of esophageal adenocarcinoma in challenging cases. AB - BACKGROUND/AIMS: Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein with vital function during human embryogenesis in terms of cellular growth and migration. Although it has minimum and undetectable expression in human adult tissues, it is highly expressed in various types of cancer. Few studies have recommend application of IMP3 expression to diagnose challenging cases of esophageal adenocarcinoma. This survey was aimed to evaluate the benefit of IMP3 expression detection in the diagnosis of esophageal adenocarcinoma and high-grade dysplasia by using immunohistochemistry (IHC). MATERIALS AND METHODS: An immunohistochemistry study of IMP3 oncofetal protein was performed on paraffin-embedded blocks of 76 cases, including Barrett's esophagus, esophageal squamous epithelium, Barrett's esophagus with low-grade dysplasia, Barrett's esophagus with high-grade dysplasia, moderately differentiated esophageal adenocarcinoma, and poorly differentiated esophageal adenocarcinoma. Two pathologists reevaluated the diagnosis and evaluated the positivity and intensity of the IHC staining as well. RESULTS: Insulin-like growth factor II mRNA-binding protein 3 expression was intensely positive in all cases of esophageal adenocarcinoma and Barrett's esophagus with HGD. Only mild positivity in 30% of Barrett's esophagus with LGD was seen. However, Barrett's esophagus and esophageal squamous epithelium had, in fact, no IMP3 expression. CONCLUSION: The percentage and intensity of IP3 IHC staining showed a significant difference between high-grade dysplasia and adenocarcinoma versus Barrett's esophagus with low-grade dysplasia, Barrett's esophagus, and esophageal squamous epithelium. Therefore, IMP3 oncofetal protein could be a very useful marker for the diagnosis of high-grade dysplasia and adenocarcinoma. However, to test the validation, a larger number samples is required. PMID- 25141313 TI - Is there a difference between capsule endoscopy and computed tomography as a first-line study in obscure gastrointestinal bleeding? AB - BACKGROUND/AIMS: Capsule endoscopy (CE) is currently recommended as the first line study in the evaluation of obscure gastrointestinal bleeding (OGIB), while computed tomography (CT) is often thought of as complementary to CE. This study evaluated CT as a first-line study in OGIB and compared it with CE. MATERIALS AND METHODS: Ninety-nine patients with OGIB who received both CE and CT were included. CT included conventional CT and CT enterography (CTE). Patients were divided into two groups: the CT before CE group (CT first group n=75) and the CE before CT group (CE first group n=24). The two groups were compared retrospectively. RESULTS: Overt OGIB was present in 92% of patients. Mucosal lesions (46%) were the most common diagnoses, while tumors accounted for 7%. The diagnostic yield of CE was significantly higher than that of CT for both groups (CT first group, p<0.001; CE first group, p=0.013). In the CT first group, the diagnostic yield using both CT and CE (48/75; 64%) was significantly higher than that for CT alone (12/75; 16%, p=0.005). In the CE first group, the diagnostic yield with both CT and CE versus CE alone was 70.9% versus 62.5%, respectively, with a significant difference (p=0.045). CONCLUSION: There was no significant clinical difference associated with the order in which the tests were performed. However, CE and CT, when used together, had a significantly greater diagnostic yield than did CE or CT when used alone. PMID- 25141314 TI - Assessment of presence and grade of activity in ileal Crohn's disease. AB - BACKGROUND/AIMS: To assess the sensitivity of magnetic resonance enterography (MRE) in the diagnosis of Crohn's disease (CD) activity and correlation between endoscopic and MRE scores in predicting the activity grade. MATERIALS AND METHODS: Twenty-five ileal CD patients with clinical and biochemical evidence of activation underwent ileocolonoscopy and MRE within 7 days of their application. Simplified endoscopic scoring of CD (SES-CD) and MRE scores was done and compared with each other and other parameters of activation (CRP, leukocyte count, platelet count). RESULTS: The sensitivity of MRE scoring was found to be 92%; however, the statistical correlation with SES-CD was not significant (p=0.83) for the grading of the activity. CONCLUSION: MRE scoring is sensitive enough to use in CD activity evaluation; however, it can not be used alone, and it is rather a complementary technique to endoscopy and is especially valuable for patients with extraluminal disease. PMID- 25141315 TI - The sensitivity of MR colonography using dark lumen technique for detection of colonic lesions. AB - BACKGROUND/AIMS: To assess the detectability of the lesions with magnetic resonance (MR) colonography using dark lumen technique that had been detected on conventional colonoscopy. MATERIALS AND METHODS: A total of 38 patients who were suspected to have a colorectal mass between April 2008 and June 2010 were included in this prospective study. Warm tap water was administered via a rectal tube to the patients in prone position. Then, axial T2 true- fast imaging with steady-state precession (FISP), axial T2 half-Fourier acquisition single-shot turbo spin-echo (HASTE), diffusion-weighted images, and T1 vibe fat suppression coronal sequences were obtained. T1 vibe fat suppression sequences on axial coronal planes were repeated after gadolinium contrast medium intravenous injection. MR images were analyzed by two radiologists concurrently. Assessments were done by comparing with conventional colonoscopy and histopathologic findings. RESULTS: Thirteen out of 20 lesions that had been detected on conventional colonoscopy were correctly obtained by MR colonography. None of the three lesions 5 mm or below was seen on MR colonography. Two out of 4 lesions measuring 6-9 mm were seen on MR colonography (50%). Eleven out of 13 lesions 10 mm and above were correctly detected on MR colonography (84.6%). Sensitivity was estimated as 65% when all lesions were evaluated together. CONCLUSION: MR colonography has a high sensitivity in the diagnosis of colonic pathologies without ionizing radiation. Future investigation will likely lead to wider acceptance of this method to detect colonic pathologies, including perhaps their use in colon cancer screening programs. PMID- 25141316 TI - Cold snare polypectomy versus hot snare polypectomy in endoscopic treatment of small polyps. AB - BACKGROUND/AIMS: The removal of small colon polyps by hot snare polypectomy (HP) is a commonly used method. Polypectomy with a cold snare (CP) has been increasingly utilized in recent years. Each method has its own advantages and disadvantages. Herein, we explored the efficacy and safety of each method. MATERIALS AND METHODS: Between January 1, 2012 and June 30, 2012, 97 consecutive patients with small colorectal polyps ranging from 5-9 mm in size were separated into either the CP or HP group. Demographic data, the duration of polypectomy, and pathology reports were recorded. RESULTS: Seventy-seven polyps were removed from 49 patients in the CP group, and 71 polyps were removed from 48 patients in the HP group. There was no significant difference between the groups with respect to gender, age distribution, number of polyps, or indications for colonoscopy. The mean polyp size was 7.21+/-1.4 mm in the CP group and 7.56+/-1.45 mm in the HP group (p=0.111). There was a significant difference in the mean procedure time between the two groups (CP, 25.71+/-4.3 sec; HP, 70.28+/-11.3 sec, p<0.001). One patient (1.3/1.4%) from each group developed post-polypectomy bleeding that required treatment. Histological evaluation revealed that 10 of the polyps (6.75%) were advanced adenomas. Pathological examination showed that the polyps were not completely removed in 4 patients (5.13%) in the CP group and 4 patients (5.63%) in the HP group (p=0.89). CONCLUSION: CP is an effective and safe method that shortens the polypectomy duration in small polyps (<=9 mm) compared to HP. PMID- 25141318 TI - Role of serum myeloperoxidase, CPK, CK-MB, and cTnI tests in early diagnosis of myocardial ischemia during ERCP. AB - BACKGROUND/AIMS: Some patients may experience retrosternal pain during ERCP, which may be a pioneer of a serious myocardial problem, and early diagnosis is very important for the prognosis and management. In the study, we aimed to investigate the role of serum cardiac biomarkers, such as myeloperoxidase (MPO), creatine phospokinase (CPK), creatine kinase- myocardial band (CK-MB), and cTnI, on early diagnosis of myocardial ischemia during endoscopic retrograde cholangio pancreaticograpy (ERCP) procedures. MATERIALS AND METHODS: In this prospective observational study, ERCP patients were separated into ischemic cardiac (n:48) and non-ischemic (n:76) groups. Serious cardiac, kidney, and liver disease patients were excluded from the study. Changes in electrocardigrapy (ECG), blood pressure, pulse rate, oxygen saturation, and serum MPO, CPK, CK-MB, and cTnI levels were investigated before and after the ERCP. Results were evaluated statistically (p<0.05). RESULTS: Mean age was 59.76+/-16.62 (55?, 69?). Only one patient had clinically unimportant retrosternal pain (0.8%). ST-elevation was detected in 10.4% (n:5), ST-depression in 12.5% (n:6), and negative-T in 31.3% (n:15) of ischemic patients during ERCP. Systolic and diastolic blood pressure and pulse rates in both groups and oxygen saturations in the ischemic group were reduced after ERCP. Significance was not detected with MPO and CPK tests. CK-MB levels showed an increase after the ERCP in the non-ischemic group (p<0.001). cTnI means were higher among the ischemics when pre- and post-ERCP periods (p:0.001) were compared. CONCLUSION: Clinically unimportant retrosternal pain, T negativity, and ST segment changes as well as reduced systolic, diastolic blood pressure, and heart rates can be seen during ERCP. MPO and CPK levels remain insignificant if myocardial injury does not develop. Increased CK-MB levels in non-ischemic patients and increased cTnI levels in ischemics may be seen. PMID- 25141317 TI - The change in microorganisms reproducing in bile and blood culture and antibiotic susceptibility over the years. AB - BACKGROUND/AIMS: Infection in the bile tract is a major cause of bacteremia and is related to high morbidity and mortality. We examined the changes in bacteria types and antibiotic susceptibility in bile cultures and simultaneous blood cultures taken from patients who applied for endoscopic retrograde cholangio pancreatography (ERCP)/percutaneous transhepatic cholangiography (PTC) for different bile duct diseases in recent years. MATERIALS AND METHODS: Bacteria types that reproduce in bile and blood cultures from patients who applied for ERCP/PTC between the years of 2007 and 2012 in our clinic were examined. All patients were evaluated together, and in addition, the periods between 2007 and 2009 (Group 1) and between 2010 and 2012 (Group 2) were compared. RESULTS: In total, 550 patients applied to this study. There were 266 patients in Group 1 and 284 in Group 2. Reproduction occurred in 77.6% of bile cultures. In the order of frequency, these cultures consisted of Escherichia coli (32.8%), Enterococcus spp. (26.2%), and Pseudomonas aeruginosa (11%). Enterococcus spp. were determined to be higher in Group 2 than Group 1 (p<0.016). Resistance to quinolones was found in 74.1% of patients, to ampicillin in 73.2%, and to cephalosporins in an average of 61%. Vancomycin was the most susceptible antibiotic (93.4%) to gram positives. Resistance to piperacillin-tazobactam and amikacin was higher in Group 2 than Group 1 (p=0.001 and p=0.003, respectively). CONCLUSION: The most frequently reproducing bacteria in the bile cultures evaluated in our hospital were Escherichia coli and Enterococcus spp. Although it was thought that the antibiotics given empirically were effective against these bacteria, there was resistancerate of 75% in our study. We determined that the first- and second-step treatment protocols must be updated. PMID- 25141319 TI - Transjugular intrahepatic portosystemic shunt: where are we? AB - BACKGROUND/AIMS: The purpose of this study was to evaluate the technical/hemodynamic success, complications, and biochemical/ hematologic consequences of transjugular intrahepatic portosystemic shunt (TIPS) created with 10-mm bare stents in our patients. MATERIALS AND METHODS: Data of 27 cirrhotic patients (18 men and 9 women; mean age, 39.7+/-18.7 years) with a median MELD score 14 (range 7-31) treated with TIPS between January 2000 and August 2010 were evaluated retrospectively. RESULTS: The indications were refractory bleeding varices in 48.2%, refractory ascites in 22.2%, and Budd-Chiari syndrome in 29.6% of the patients. Technical and hemodynamic success rates were 96.3% and 92.3%, respectively. Mean portosystemic pressure gradient decreased from 21.5+/-5.3 mm Hg to 9+/-2.7 mm Hg (p<0.05). The rate of primary stent patency was 76.9% 1 year after the procedure. No statistically significant difference in shunt dysfunction was found between the groups of patients treated for Budd-Chiari syndrome and other indications (p>0.05). One patient (3.7%) had shunt dysfunction due to thrombosis within 24 hours. New and/or worsening hepatic encephalopathy occurred in 34.6% of patients. Increased age (>=40 years) was significantly related to hepatic encephalopathy in both univariate and multivariate analyses (p<0.05). Thirty-day mortality rate and 1-year transplant-free survival rate were 0% and 80.7%, respectively. CONCLUSION: Transjugular intrahepatic portosystemic shunt procedure is a safe treatment for many patients with cirrhosis, but post procedure hepatic encephalopathy and shunt dysfunction are still problems. Especially, patient age should be taken into consideration in predicting hepatic encephalopathy risk. PMID- 25141320 TI - Public awareness of hepatitis B infection in Turkey as a model of universal effectiveness in health care policy. AB - BACKGROUND/AIMS: This study aimed to analyze the knowledge and awareness of hepatitis B virus (HBV) infection in an HBV-infected Turkish population as a model for global health care practice and to evaluate potential factors associated with the disease spread and its prevention. MATERIALS AND METHODS: A cross-sectional survey was conducted in Ankara University School of Medicine, Liver Disease Outpatient Clinic between August 2012 and March 2013. The survey queried sociodemographics, knowledge, and awareness of HBV infection, transmission, and consequences and common practices and behaviors. RESULTS: A total of 181 patients were surveyed (median age=49 years); 91 (51%) had "advanced" education levels (high school, bachelor's, graduate degree), 108 (60%) had knowledge about HBV infection and transmittance, and 130 (72%) were aware of the ill consequences of HBV infection. Also, 120 (66%) had vaccinated their family members against HBV infection. Participants with knowledge of HBV infection transmittance were more likely to vaccinate their family members compared to unknowledgeable participants (p=0.015). Participants with "advanced" education levels were also more likely to vaccinate family members (p=0.047). CONCLUSION: Promoting better awareness of HBV and endorsing mass educational interventions may be useful strategies to prevent the spread of HBV infection. Such strategies may be recommended as cost-effective global health care practices in HBV endemic areas. PMID- 25141321 TI - Significance of appetite hormone ghrelin and obestatin levels in the assessment of the severity of acute pancreatitis. AB - BACKGROUND/AIMS: Due to risk of morbidity and mortality, various tests and scoring systems used in the assessment of the diagnosis and severity of acute pancreatitis disease are gaining more importance every day. Most of the current scoring systems, validated by various parameters, have a sophisticated and complex structure. Research is ongoing to establish a method to diagnose the disease and determine the severity by using different and simple parameters. In this trial, we aimed to investigate the role of the orexigenic "ghrelin" and anorexigenic "obestatin" hormones, if any, on the diagnosis and assessment of the severity of acute pancreatitis. MATERIALS AND METHODS: A total of 30 patients hospitalized between September 2009 and September 2010 with a diagnosis of acute pancreatitis (AP) and 25 healthy volunteers were enrolled in the trial with a prospective and randomized design. The patients were classified in two groups, mild (Ranson <=3 and / or Apache II <=8) and severe (Ranson >3 and/or Apache II >8) cases, as per the Ranson and Apache-II criteria; the ghrelin and obestatin levels in blood samples obtained from the patients were measured using the ELISA method. RESULTS: Twenty-two of the 30 patients (73%) were regarded as mild pancreatitis cases, while 8 cases (27%) were diagnosed as severe pancreatitis. Comparison of the mild and severe pancreatitis groups did not reveal a statistical difference between the two groups in terms of acylated and de acylated ghrelin values on presentation and following the initiation of oral feeding. Similarly, no significant difference was found in the comparison of the patient and the control groups in terms of acylated and de-acylated ghrelin values on presentation (p=0.863). On the other hand, acylated and de-acylated ghrelin values after initiation of oral feeding were observed to be higher in the patient group (p=0.001, p=0.000). Comparison of these two groups revealed a significant difference in obestatin values, both on presentation and after initiation of oral feeding (p=0.002 and p=0.000). CONCLUSION: Consistently high serum ghrelin values during pancreatic inflammation suggest that ghrelin may be used as an adjunctive parameter in the monitoring of the course of the disease. On the other hand, high obestatin values in patients on presentation indicate that this hormone is a more significant parameter in terms of diagnosis. However, no correlation was established between these two peptide hormones and the severity of AP. PMID- 25141322 TI - Primary mesenchymal tumors of the colon: a report of three cases. AB - Primary mesenchymal tumors of the colon are extremely rare tumors among soft tissue sarcomas. These tumors are more aggressive and have poorer prognosis than adenocarcinoma of the colon. Here, we presented 3 cases of primary mesenchymal tumors of the colon. Their histopathological diagnoses are leiomyosarcoma, pleomorphic liposarcoma, and desmoplastic small round cell tumor, respectively. The rarity of primary mesenchymal tumors of the colon makes it difficult to approach the treatment and predict the prognosis of these rare tumors. PMID- 25141323 TI - Mutatis mutandis: are we diagnosing too many people with non-celiac gluten sensitivity? Multiple case report. AB - We report three patients presenting with gluten-related signs and symptoms. Since villous height/crypt depth ratio, intraepithelial lymphocyte count, and serum antibody tests were not diagnostic for celiac disease (CD), a diagnosis of non celiac gluten sensitivity (NCGS) was suggested. On the other hand, antibodies suggestive for CD surprisingly showed positive results in the duodenal biopsy organ culture of all three cases. The reported cases suggest the precious potential role that organ culture systems may play in differentiating CD from NCGS. This method should be recommended when gluten-related disorders are suspected in order to reduce the inappropriate diagnosis of NCGS. PMID- 25141324 TI - Unusual presentations of eosinophilic gastroenteritis: two case reports. AB - Eosinophilic gastroenteritis is a rare disease that is characterized by eosinophil infiltration in one or multiple segments of the gastrointestinal tract. The etiology of this condition remains unknown. Eosinophilic gastroenteritis has heterogeneous clinical manifestations that depend upon the location and depth of infiltration in the gastrointestinal tract, and eosinophilia may or may not be present. This article reports two cases of eosinophilic gastroenteritis. The first is that of a 49-year-old woman with abdominal pain, ascites, eosinophilia, and a history of asthma. The second case is that of a 69-year-old male with a history of loss of appetite, belching, postprandial fullness, heartburn, and a 5-kilogram weight loss over a period of 9 months; ultimately, the patient was diagnosed with a gastric outlet obstruction due to pyloric stenosis. The rare character of eosinophilic gastroenteritis and its varied clinical presentations often lead to delayed diagnoses and complications. Case reports may help to disseminate knowledge about the disease, thereby increasing the likelihood of early diagnosis and intervention to prevent complications. PMID- 25141325 TI - Hepatocellular carcinoma presenting as a huge intra-abdominal mass: a case report. AB - Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and is generally associated with hepatitis B or C virus-related cirrhosis. A giant intra-abdominal HCC mass that fills nearly the whole abdomen is not often reported in the literature. In this report, we present a case in which a patient with hepatitis B developed a giant intra-abdominal mass that originated from segment three of the liver and infiltrated the stomach and transverse colon. We were able to resect the tumor without leaving any tumor tissue behind. Although HCC presenting as a huge mass with invasion of the gastrointestinal tract is uncommon, this pathology should be considered in the differential diagnosis of giant intra-abdominal masses. The case presented here also indicates that surgical resection is possible in selected patients. PMID- 25141326 TI - Evaluation of patients with positive anti-mitochondrial antibody in laboratory conditions. PMID- 25141327 TI - Cannabinoid-induced acute pancreatitis. PMID- 25141328 TI - Diagnosis of helicobacter pylori infection. PMID- 25141329 TI - Acute liver failure; what is different in Turkey and some remarks. PMID- 25141330 TI - Paraneoplastic presentation of cholestatic jaundice in renal cell carcinoma. PMID- 25141331 TI - Correct determination of abdominal fat accumulation. PMID- 25141332 TI - Do we have to worry for thrombocytopenia during treatment of hepatitis C. PMID- 25141333 TI - Fecal microbiota transplant in immunocompromised patients: Encouraging results in a vulnarable population. PMID- 25141334 TI - How will I know whether "an apple is ripe or rotten"? A new proposed composite algorithm to predict acute liver failure in patients with drug-induced liver injury. PMID- 25141335 TI - "Old classic cars" are hidden treasures: colorectal cancer screening should be considered in unscreened persons over age 75. PMID- 25141337 TI - Thermopower of benzenedithiol and C60 molecular junctions with Ni and Au electrodes. AB - We have performed thermoelectric measurements of benzenedithiol (BDT) and C60 molecules with Ni and Au electrodes using a home-built scanning tunneling microscope. The thermopower of C60 was negative for both Ni and Au electrodes, indicating the transport of carriers through the lowest unoccupied molecular orbital in both cases, as was expected from the work functions. On the other hand, the Ni-BDT-Ni junctions exhibited a negative thermopower, whereas the Au BDT-Au junctions exhibited a positive thermopower. First-principle calculations revealed that the negative thermopower of Ni-BDT-Ni junctions is due to the spin split hybridized states generated by the highest occupied molecular orbital of BDT coupled with s- and d-states of the Ni electrode. PMID- 25141338 TI - NMR nanoparticle diffusometry in hydrogels: enhancing sensitivity and selectivity. AB - From the diffusional behavior of nanoparticles in heterogeneous hydrogels, quantitative information about submicron structural features of the polymer matrix can be derived. Pulsed-gradient spin-echo NMR is often the method of choice because it measures diffusion of the whole ensemble of nanoparticles. However, in (1)H diffusion-ordered spectroscopy (DOSY), low-intensity nanoparticle signals have to be separated from a highly protonated background. To circumvent this, we prepared (19)F labeled, PEGylated, water-soluble dendritic nanoparticles with a (19)F loading of ~7 wt % to enable background free (19)F DOSY experiments. (19)F nanoparticle diffusometry was benchmarked against (1)H diffusion-T2 correlation spectroscopy (DRCOSY), which has a stronger signal separation potential than the commonly used (1)H DOSY experiment. We used bootstrap data resampling to estimate confidence intervals and stabilize 2D Laplace inversion of DRCOSY data with high noise levels and artifacts, allowing quantitative diffusometry even at low magnetic field strengths (30 MHz). The employed methods offer significant advantages in terms of sensitivity and selectivity. PMID- 25141339 TI - Effects of caste on the expression of genes associated with septic injury and xenobiotic exposure in the Formosan subterranean termite. AB - As social insects, termites live in densely populated colonies with specialized castes under conditions conducive to microbial growth and transmission. Furthermore, termites are exposed to xenobiotics in soil and their lignocellulose diet. Therefore, termites are valuable models for studying gene expression involved in response to septic injury, immunity and detoxification in relation to caste membership. In this study, workers and soldiers of the Formosan subterranean termite, Coptotermes formosanus, were challenged by bacterial injection or by no-choice feeding with a sublethal concentration (0.5%) of phenobarbital. Constitutive and induced expression of six putative immune response genes (two encoding for lectin-like proteins, one for a ficolin precursor, one for the Down syndrome cell adhesion molecule, one for a chitin binding protein, and one for the gram-negative binding protein 2) and four putative detoxification genes (two encoding for cytochrome P450s, one for glutathione S-transferase, and one for the multi antimicrobial extrusion protein), were measured via quantitative real time polymerase chain reaction and compared within and among 1) colonies, 2) treatment types and 3) castes via ANOVA. Eight genes were inducible by septic injury, feeding with phenobarbital or both. Colony origin had no effect on inducibility or differential gene expression. However, treatment type showed significant effects on the expression of the eight inducible genes. Caste effects on expression levels were significant in five of the eight inducible genes with constitutive and induced expression of most target genes being higher in workers than in soldiers. PMID- 25141342 TI - The crystal structure of Li2B3PO8 with the 2D-linkage of BO3, BO4 and PO4 groups. AB - The crystal structure of Li2B3PO8 was determined by X-ray diffraction of a single crystal prepared by slow cooling from 943 K to 873 K. Li2B3PO8 crystallizes in a triclinic cell (space group P1[combining macron], Z = 8). The sheets of [B3PO8](2 ) formed by the linkage of triangular BO3 and tetrahedral BO4 and PO4 groups stack along the b-axis direction. PMID- 25141340 TI - Integrative advances for OCT-guided ophthalmic surgery and intraoperative OCT: microscope integration, surgical instrumentation, and heads-up display surgeon feedback. AB - PURPOSE: To demonstrate key integrative advances in microscope-integrated intraoperative optical coherence tomography (iOCT) technology that will facilitate adoption and utilization during ophthalmic surgery. METHODS: We developed a second-generation prototype microscope-integrated iOCT system that interfaces directly with a standard ophthalmic surgical microscope. Novel features for improved design and functionality included improved profile and ergonomics, as well as a tunable lens system for optimized image quality and heads-up display (HUD) system for surgeon feedback. Novel material testing was performed for potential suitability for OCT-compatible instrumentation based on light scattering and transmission characteristics. Prototype surgical instruments were developed based on material testing and tested using the microscope integrated iOCT system. Several surgical maneuvers were performed and imaged, and surgical motion visualization was evaluated with a unique scanning and image processing protocol. RESULTS: High-resolution images were successfully obtained with the microscope-integrated iOCT system with HUD feedback. Six semi transparent materials were characterized to determine their attenuation coefficients and scatter density with an 830 nm OCT light source. Based on these optical properties, polycarbonate was selected as a material substrate for prototype instrument construction. A surgical pick, retinal forceps, and corneal needle were constructed with semi-transparent materials. Excellent visualization of both the underlying tissues and surgical instrument were achieved on OCT cross section. Using model eyes, various surgical maneuvers were visualized, including membrane peeling, vessel manipulation, cannulation of the subretinal space, subretinal intraocular foreign body removal, and corneal penetration. CONCLUSIONS: Significant iterative improvements in integrative technology related to iOCT and ophthalmic surgery are demonstrated. PMID- 25141343 TI - Rainbow trout provide the first experimental evidence for adherence to a distinct Strouhal number during animal oscillatory propulsion. AB - The relationship between tail (or wing) beat frequency (f(tail)), amplitude (A) and forward velocity (U) in animals using oscillatory propulsion, when moving at a constant cruising speed, converges upon an optimum range of the Strouhal number (St = f(tail) . A/U). Previous work, based on observational data and supported by theory, shows St falling within the broad optimum range (0.2=20 or <20 sessions, respectively. INTERVENTIONS: Participants were guided through a standardized 90-min yoga class performed in a hot environment using Bikram's Standard Beginning Dialogue, while expired gas was collected and heart rate was recorded. OUTCOME MEASURES: Energy expenditure, calculated via oxygen uptake, and heart rate were determined for each posture and transition period. In addition, sweat rate and core temperature were recorded for each participant. RESULTS: Mean (+/-SD) relative VO2 for the entire 90-min session was 9.5 +/- 1.9 mL * kg-1 * min-1, ranging from 6.0 to 12.9 mL * kg-1 * min-1. Mean absolute energy expenditure was 286 +/- 72 kcals, ranging from 179 to 478 kcals. Independent sample t tests revealed significant differences (P < .05) in relative energy expenditure, heart rate, ending core temperature, and sweat rate between experience levels. Mean relative energy expenditure was 3.7 +/- 0.5 kcal/kg in novice practitioners and 4.7 +/- 0.8 kcal/kg in experienced practitioners. Percentage of predicted maximum heart rate and sweat rate were 72.3% +/- 10.6% and 0.6 +/- 0.2 kg/h in novice practitioners and 86.4% +/- 5.2% and 1.1 +/- 0.5 kg/h in experienced participants. All postures were classified as light-to moderate intensity according to the American College of Sports Medicine (ACSM) standards. CONCLUSIONS: Bikram yoga meets requirements for exercise of light-to moderate intensity and, theoretically, could be used for weight maintenance or weight loss if practiced several times per week. PMID- 25141360 TI - Randomized, controlled trial of qigong for treatment of prehypertension and mild essential hypertension. AB - CONTEXT: Hypertension treatments include sodium restriction, pharmacological management, and lifestyle modifications. Although many cases of hypertension can be controlled by medication, individuals may experience side effects or incur out of-pocket expenses, and some may not comply with the treatment regimen. Although some previous studies have shown a favorable effect for qigong on hypertension, well-designed, rigorous trials evaluating the effect of qigong on hypertension are scarce. OBJECTIVE: This study aimed to evaluate the effect of qigong on prehypertension and mild hypertension and to calculate a sample size for a subsequent randomized, clinical trial (RCT). DESIGN: Participants were randomized to a qigong group or an untreated control group. SETTING: This study was conducted at the Oriental Medical Center of Dongeui University, in the Republic of Korea. PARTICIPANTS: Participants were individuals between the ages of 19 and 65 y with systolic blood pressure (SBP) between 120 and 159 mm Hg and/or diastolic blood pressure (DBP) between 80 and 99 mm Hg. INTERVENTION: The qigong group attended qigong classes 3 */wk and performed qigong at home at least 2 */wk. Participants in the control group did not receive any intervention for hypertension. OUTCOME MEASURES: Outcome measures for this study were (1) changes in blood pressure (BP); (2) quality of life (QOL) using 2 surveys: the Medical Outcomes Study (MOS) 36-item short form (SF-36) (Korean version) and the Measure Yourself Medical Outcome Profile 2 (MYMOP2); and (3) hormone levels. RESULTS: Of 40 participants, 19 were randomly assigned to the qigong group, and 21 were assigned to the control group. After 8 wk, significant differences were observed between the qigong and the control groups regarding changes in SBP (P = .0064) and DBP (P = .0003). Among the categories of the MYMOP2 questionnaire, only wellbeing was significantly different between the 2 groups (P = .0322). The qigong group showed a significantly greater improvement in the physical component score of the SF-36 compared with the control group (P = .0373). Regarding changes in hormone levels, there was no significant difference between the qigong and the control groups. This pilot study demonstrates that regarding sample size, a RCT evaluating the effect of qigong on hypertension should include 22 participants based on DBP and 285 participants based on SBP in each group, thus allowing for a loss to follow-up rate of 20%. CONCLUSION: The results indicate that qigong may be an effective intervention in reducing BP in prehypertension and mild hypertension. Further studies should include an appropriate sample size and methodology to determine the mechanism of qigong on BP. PMID- 25141361 TI - Effects of moxibustion or acupoint therapy for the treatment of primary dysmenorrhea: a meta-analysis. AB - CONTEX: Primary dysmenorrhea (PD) is a common gynecological syndrome that is characterized by cramping in the lower abdomen during menstruation, particularly during puberty. Treatment for PD includes a variety of pharmacological, nonpharmacological, and surgical options. Although studies supporting use of traditional Chinese medicine (TCM) have helped in the proliferation of its comprehensive therapy, their results do not determine with certainty whether moxibustion and acupoint therapy are better for the treatment of PD than nonacupuncture-related therapy. OBJECTIVE: The study intended to compare the effectiveness of moxibustion and acupoint therapy- such as sandwiched moxibustion, moxibustion, acupuncture, eye of floating needle, and acupoint application-with other therapeutic methods for the treatment of PD. DESIGN: Six electronic databases-PubMed, Web of Science, the Chinese Biomedical Literature Database (CBM), the Chinese Journal Full-text Database (CNKI), the Chinese Science and Technology Journal Full-text Database (VIP), and Chinese Wanfang Data were searched electronically, from inception to December, 2012, to find randomized, controlled trials (RCTs). Relevant references in articles used in the current study were searched manually. Literature was screened, data were extracted, and the methodological quality of the included studies was assessed. Then, meta-analyses were performed. SETTING: All of processes of this study were conducted at Tianjin University of Traditional Chinese Medicine and School of Nursing at Tianjin Medical University. PARTICIPANTS: The research team divided the selected RCTs into 2 groups based on the type of PD that the participants had: (1) the undifferentiated type group (UTG) and (2) the cold-damp stagnation type group (CDSTG). OUTCOME MEASURES: The research team measured total effective rate, symptom score, and variation of peripheral blood prostaglandin F2alpha (PGF2alpha). RESULTS: A total of 20 RCTs, involving 2134 participants, were included in the current study. Results of the metaanalysis showed that (1) the total efficacy for the 2 studied interventions was better, with a statistically significant difference from that of the control methods: degrees of freedom (df) = 14, relative risk (RR) = 1.19, 95% confidence interval (95% CI) = (1.14 - 1.24), P < .000 for the UTG, and df = 4, RR = 1.15, 95% CI (1.02 - 1.29), P = .03 for the CDSTG; (2) the studied interventions were better than the control methods, with statistically significant differences, in relieving the severity of symptoms of PD: df = 3, mean difference (MD) = 3.20, 95% CI (2.36 - 4.04), P < .000 for the UTG and df = 1, MD = 2.09, 95% CI (0.16 - 4.02), P = .03 for the CDSTG; and (3) no statistical difference existed between the intervention and control methods groups in the reduction of the level of peripheral blood PGF2alpha: df = 2, standardized mean difference (SMD) = 0.13, 95% CI (-0.13 - 0.39), P = .32. CONCLUSIONS: Moxibustion and acupoint therapy can relieve pain effectively for individuals with PD, and these treatments have advantages in overall efficiency. Because of limitations on the quantity and quality of the included studies and the lack of a large, multicenter study, the research team's conclusion has yet to be substantiated. PMID- 25141362 TI - Use of movement therapies and relaxation techniques and management of health conditions among children. AB - CONTEXT: Use of complementary and alternative medicine (CAM) by children under 18 y of age in the United States is becoming more prevalent. According to an analysis of procedures in chiropractic practices in 2010, more than 96% of chiropractors in the United States recommended use of movement therapies (MT) and relaxation techniques (RT) to their patients. The extent of use of these methods as treatment options for specific health conditions in children, however, has been underexplored in the United States. OBJECTIVES: The current study assessed use of MT and RT in children for treatment of various health conditions, as reported in the 2007 National Health Interview Survey (NHIS), and also examined variations in use across various sociodemographic categories. DESIGN: Secondary data from the 2007 National Health Interview Survey (NHIS) Child Alternative Medicine file were analyzed, and the research team generated weighted frequencies and inferential statistics. OUTCOME MEASURES: Odds ratios (OR) and 95% confidence intervals (CI) were computed through binary logistic regression to assess use of MT and RT as functions of various sociodemographic variables. RESULTS: Within the 12 mo prior to the survey, MT and RT use was reported by 2.5% and 2.9% of respondents, respectively. MT, primarily yoga, was used for the control and reduction of anxiety and stress (31.4%), asthma (16.2%), and back/neck pain (15.3%). Alternatively, RT, such as controlled breathing exercises (2.1%) and meditation (2.3%), was used for anxiety and stress (41.4%) and attention-deficit disorders (ADDs) (16.0%). Although data screening did not produce obvious predictors for RT use, age, gender, race/ethnicity, and parents' education levels were potential predictors of MT use. For example, respondents aged <10 y reported lower MT use than those >10 y (OR = 0.4; 95% CI, 0.3-0.6), and males reported lower MT use than females (OR = 0.5; 95% CI, 0.3-0.7). CONCLUSION: MT and RT are used by several million children in the United States each year. The current research suggests that early training on MT and RT can be seen as a useful tool that can help prevent or manage certain health problems. In addition to an examination of their role in primary prevention, the use of MT and RT should be explored further to determine how these therapies work with respect to specific health conditions. PMID- 25141363 TI - Jeffrey Dach, MD: the transition to a natural medicine practice. PMID- 25141364 TI - Cardiovascular disease and statin drugs. PMID- 25141365 TI - Matthew Budoff, MD: the cardiovascular effects of garlic supplementation. PMID- 25141366 TI - The cholesterol and statin controversy: the new 2013 statin-cholesterol guidelines. PMID- 25141367 TI - A novel, multi-ingredient supplement to manage elevated blood lipids in patients with no evidence of cardiovascular disease: a pilot study. AB - CONTEXT: Recent changes in usage guidelines have created the potential for millions more Americans to be prescribed statin medications. Caution should be advised because the risk of adverse effects of statins may outweigh their benefits and preclude their preventive use for patients without confirmed cardiovascular disease (CVD) who present with elevated blood lipids. However, statins have shown some benefit in primary CVD prevention. Red yeast rice (RYR) is a dietary supplement that has been demonstrated to reduce low-density lipoprotein (LDL) cholesterol levels in blood and omega-3 polyunsaturated fatty acids have been shown to reduce blood levels of triglycerides (TGs). Although effective, quality control issues aggravate risk of adverse effects for both of these supplements. Furthermore, low dosages per capsule, which require patients to manage and consume many capsules per day, also may reduce patient compliance to supplementation regimens. OBJECTIVES: The authors' objective was to determine the effects of a multi-ingredient supplement (MIS) featuring RYR for primary support of cardiovascular (CV) health in patients who present no CVD history or symptoms other than elevated blood lipids. The MIS was formulated intentionally with a lower dosage of RYR than that used in prior studies in order to reduce the occurrence of adverse effects. Secondary to the objective of managing blood lipids, the authors were interested in determining the effects of the MIS in combination with a high-potency omega-3 polyunsaturated fatty acid supplement and its effect on TG levels and observing whether adverse effects would inhibit patient compliance. DESIGN: The research team designed an open-label pilot study following a pre-post pragmatic design. Setting * The study took place at 2 primary care settings. PARTICIPANTS: Nineteen patients with hypercholesterolemia were participants in the study. All participants were required to confirm that they had not taken any other pharmaceutical or supplement therapy to treat cholesterol for at least 30 d prior to baseline, establishing a washout period. At completion of the intervention, 3 participants were excluded for noncompliance with the protocol, although they had taken the supplements as directed. INTERVENTION(S): The recommended serving of the MIS supplement consisted of 1 softgel that contained 9 ingredients: a proprietary blend of RYR, bioflavonoids, polycosanol, 525 mg omega-3 fatty acids in the natural TG form (294 mg eicosapentaenoic acid [EPA], 147 mg docosahexaenoic acid [DHA]) as well as other supporting ingredients, resveratrol, coenzyme Q10 (CoQ10), folic acid vitamin B3 (niacin), B6, B12, and black pepper. Each serving of the omega-3 supplement contained 834 mg of omega-3 polyunsaturated fatty acids in the natural TG form (484 mg EPA, 234 mg DHA) and 33 IU vitamin E, (D-alpha-tocopherol). The studys participants were assigned to a group based on their initial TG levels. Participants with TG levels <140 mg/dL took the MIS only, and participants whose initial TG levels exceeded 140 mg/dL were assigned to take both the MIS and the omega-3 supplement, receiving 1384 mg of omega-3 daily (778 mg EPA, 381 mg DHA). All participants confirmed by poststudy survey that they took the recommended serving of 1 softgel/d of the assigned supplement(s) for a minimum of 30 d. OUTCOME MEASURE(S): At baseline and follow-up, standard venous blood labs were drawn and processed at nationally accredited labs. Although not standardized, all reports contained: total cholesterol, high-density lipoprotein (HDL), LDL, and TG levels. The research team acknowledges that this lack of standardization and additional lipid data, such as very low-density lipoprotein, is a limitation of the study. RESULTS: Total cholesterol and LDL decreased significantly, by 12.0% (P = .0004) and 17.3% (P = .0001), respectively, for the 16 participants taking the MIS supplement. Participants with an LDL at baseline greater than 145 mg/dL (n = 7) benefited even more, with total cholesterol and LDL decreasing significantly by 17.1% (P = .01) and 24.5% (P = .0014), respectively. Although the results were not significant, adding the omega-3 supplement to the protocol resulted in a decrease in the TGs of the subgroup taking both supplements (n = 8), with that measure decreasing by 13.1% (P = .27) from baseline compared with a decrease of 2% (P = .95) for all participants. The subgroup taking both the MIS and omega-3 supplements experienced similar decreases in total cholesterol and LDL as participants taking only the MIS. No side effects were reported by participants, and all participants completed the assigned protocol. CONCLUSIONS: The MIS supplement decreased total cholesterol and LDL significantly and offers a promising therapy for the management of cholesterol that may enable better patient compliance. The addition of an omega-3 supplement also decreased TGs in the subgroup that received both therapies, although this decrease was not significant, potentially because of the underpowered size of the subgroup. The research team plans future studies with more robust lipid testing and larger numbers of participants to support the findings of the current study. PMID- 25141368 TI - Protective effects of melatonin therapy in model for neonatal hyperoxic lung injury. AB - CONTEXT: Bronchopulmonary dysplasia (BPD) is a common outcome of premature birth. Currently, no effective preventive therapy is available for BPD, but the major role of O2 toxicity in the development of BPD has gained attention, particularly for developing new antioxidants for prevention. The major protective mechanism of melatonin (MT) includes free-radical scavenging activity and activation of the cyclooxygenase-prostoglandin enzyme system. OBJECTIVE: The aim of this study was to evaluate the effects of MT on cytoprotection and healing in a model of hyperoxic lung injury in newborn rats. METHODS: This is a case-control study design. SETTING: The study occurred at the Gulhane Military Medical Academy in Ankara, Turkey. INTERVENTION: A total of 60 newborn pups from dated, Sprague Dawley, pregnant rats were divided equally into 3 groups as follows: (1) control group, (2) hyperoxia-exposed group, and (3) hyperoxia-exposed plus MT-treated group (MT group). Hyperoxia was performed by placing these pups in an oxygen chamber for 14 d during which oxygen was continuously delivered. OUTCOME MEASURES: At the end of the 14 d, lung specimens were collected and evaluation of the lamellar-body count and determination of histopathological scores were performed. Also, the activities of superoxide dysmutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were assessed. RESULTS: The histopathological scores of the MT group were significantly lower than those of the hyperoxia-exposed group. The mean lamellar-protein and radial-alveolar counts in the MT group were found to be significantly higher than those of the hyperoxia exposed group. Also, SOD and GSH-Px levels were significantly higher and MDA levels were significantly lower in the MT group compared with the hyperoxia exposed group. CONCLUSION: MT therapy was found to have a protective effect in a model for hyperoxic lung injury in neonatal rats. Therefore, the research team suggests that MT therapy may be used for prevention of BPD in preterm infants after confirmation of this data by future clinical studies. PMID- 25141369 TI - Personalized medicine: a confluence of traditional and contemporary medicine. AB - CONTEXT: Traditional systems of medicine have attained great popularity among patients in recent years. Success of this system in the treatment of disease warrants consideration, particularly in cases for which conventional medicine has been insufficient. OBJECTIVE: This study investigates the similarities in principles and approaches of 3 traditional systems and explores whether conventional medicine is able to exploit the advantages of traditional systems. DESIGN: This study first identifies and explores the advantages of 3 well-known systems-traditional Iranian medicine (TIM), ayurveda, and traditional Chinese medicine (TCM)-that are similar in their basic principles and methods. Second, it clarifies whether and how conventional medicine could exploit the advantages of traditional systems as it modernizes, to become more personalized. Finally, this study investigates the possibility that conventional medicine could benefit from traditional typology to improve its personalization. RESULTS: The acknowledgment of the unity of humans and nature, applying rational methods, and personalized approaches is fundamentally similar in the 3 systems. Additionally, they all promote the holistic view that health is harmony and disease is disharmony of the body. Other similarities include their recognition of the unique nature of every person and their categorization of people into different body types. Although conventional medicine has mostly failed to incorporate the advantages of traditional medicine, its integration with traditional medicine is achievable. For instance, exploiting traditional typologies in genomic and other studies may facilitate personalization of conventional medicine. CONCLUSION: From its review, the research team concludes that prospects are bright for the integration of traditional and conventional medicines and, consequently, for a dramatic improvement in health systems. PMID- 25141370 TI - Genomics and the convergence of personalized medicine in modern and traditional medicine. PMID- 25141371 TI - Evaluating the efficacy of Tui Na in treatment of childhood anorexia: a meta analysis. AB - CONTEXT: Medical practitioners are now seeing more children younger than 15 y who are developing childhood anorexia. Hua Tuo chiropractic treatments are an ancient and practical massage therapy and are a type of Tui Na therapy, which has been used for curing childhood anorexia for thousands of years in China. Research literature suggests that chiropractic care produces outcomes at least comparable with alternative treatments. OBJECTIVE: The research team intended to perform a systematic review to identify and synthesize evidence on the efficacy of Tui Na for treatment of childhood anorexia. DESIGN: Systematic searches were conducted for studies evaluating Tui Na therapy in electronic databases MEDLINE, EMBASE, PsychINFO, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, the Midwives Information and Resource Service, the Health Management Information Consortium, the Health Management and Information Service, PubMed, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), the Chinese Scientific Journal Database VIP, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Chinese Clinical Trial Register-from inception to November 2011. The research team hand-searched reference lists and journals, extracted data from the papers, and assessed the quality of the research. PARTICIPANTS: Participants of the reviewed studies were infants and children younger than 15 y. RESULTS: Of the 109 papers identified, 3 papers reported on randomized, controlled trials (RCTs) involving 332 patients; 45 covered cohort or quasi-experimental studies; and 61 discussed nonintervention studies. Meta-analysis results from the 3 RCTs showed that Tui Na can improve the curative effect compared with oral medicine that is used for infants and young children with anorexia and can also increase a child's weight. CONCLUSIONS: The level of evidence reported was mixed, but given the available evidence, the research team concluded that Tui Na therapy was a viable intervention that could benefit infants and young children with anorexia. No serious adverse events were reported. Larger randomized, controlled trials are required to explore the effects of Tui Na therapy for treatment of childhood anorexia further. PMID- 25141372 TI - Kelly Heim, PhD: cardioprotective effects of polyphenol consumption. PMID- 25141376 TI - The making of the master clock. AB - A genetic basis for the anatomic master circadian clock in mammals has been found. PMID- 25141375 TI - Reconceiving the hippocampal map as a topological template. AB - The role of the hippocampus in spatial cognition is incontrovertible yet controversial. Place cells, initially thought to be location-specifiers, turn out to respond promiscuously to a wide range of stimuli. Here we test the idea, which we have recently demonstrated in a computational model, that the hippocampal place cells may ultimately be interested in a space's topological qualities (its connectivity) more than its geometry (distances and angles); such higher-order functioning would be more consistent with other known hippocampal functions. We recorded place cell activity in rats exploring morphing linear tracks that allowed us to dissociate the geometry of the track from its topology. The resulting place fields preserved the relative sequence of places visited along the track but did not vary with the metrical features of the track or the direction of the rat's movement. These results suggest a reinterpretation of previous studies and new directions for future experiments. PMID- 25141377 TI - [In process citation]. PMID- 25141378 TI - Access to primary and preventive health care across states prior to the coverage expansions of the Affordable Care Act. AB - One goal of health insurance is ensuring people have timely access to primary and preventive care. This issue brief finds wide differences in primary and preventive care access among adults under age 65--across states and within states by income--before the Affordable Care Act's major insurance expansions took effect. When comparing experiences of adults with insurance, the analysis finds that state and income differences narrow markedly. When insured, middle- and lower-income adults across states are far more likely to have a regular source of care, receive preventive care, and be able to afford care when needed. The findings highlight the potential of expanding health insurance to reduce the steep geographic and income divide in primary and preventive care that existed across the country before 2014. Success will depend on the participation of all states. This brief offers baseline data for states and the nation to track and assess change. PMID- 25141379 TI - The author's reply. PMID- 25141380 TI - Impact. PMID- 25141381 TI - Author reply: To PMID 24552234. PMID- 25141382 TI - CDC issues new HIV testing recommendations. PMID- 25141383 TI - Transmission. Online chat rooms, video games help increase HIV testing in MSM. PMID- 25141384 TI - Research. Program increases black, Hispanic participation in studies. PMID- 25141385 TI - Prisons. Inmate failed to show lapse in medication was indifference. PMID- 25141386 TI - Courts are not considered 'covered entities' under HIPPA. PMID- 25141387 TI - SSI. Doctor's opinion based on subjective evidence, not record. PMID- 25141388 TI - Testing. Court erred in requiring convicted woman to submit to test. PMID- 25141389 TI - The effects of stimulant medications for ADHD. PMID- 25141390 TI - Regional variation in health care: physician beliefs or patient preferences? PMID- 25141391 TI - The recent slowdown in health care spending: explanations and predictions. PMID- 25141395 TI - Keeping workers safe and healthy. PMID- 25141396 TI - Nurses' micro behaviours undermine public image. PMID- 25141397 TI - Fundamentally flawed arguments. PMID- 25141399 TI - Election publication praised. PMID- 25141401 TI - The president comments. PMID- 25141400 TI - Debating voluntary euthanasia. PMID- 25141402 TI - New format for NZNO conference and annual general meeting. PMID- 25141403 TI - Nursing workforce strategy vital for health. PMID- 25141404 TI - Survey shows nurses' hand hygiene improving. PMID- 25141405 TI - Hundreds more looking for new graduate positions. PMID- 25141406 TI - Complaints about nurses nearly double. PMID- 25141407 TI - Research reveals violence in health. PMID- 25141408 TI - Health budget falls short of growing costs. PMID- 25141409 TI - Patient portals create new health partnerships. PMID- 25141410 TI - Health and safety bill needs to be strengthened - NZNO. PMID- 25141411 TI - Maori and Pacific situation unchanged. PMID- 25141412 TI - TPPA 'threatens future of health in New Zealand'. PMID- 25141413 TI - Celebrating nursing achievements. PMID- 25141414 TI - Honouring 10 years' International Red Cross service. PMID- 25141415 TI - Assaults leave nurses fearful. PMID- 25141416 TI - Nurses 'encouraged to report'. PMID- 25141417 TI - Winning, when dealing with bullies. PMID- 25141418 TI - I found myself in nursing. PMID- 25141419 TI - Wanted: a primary health care approach. PMID- 25141420 TI - NPNZ conference focuses on prescribing. PMID- 25141421 TI - Nursing in the thick of battle. PMID- 25141422 TI - Learning from the experiences of disabled nurses. PMID- 25141423 TI - Dealing with discrimination. PMID- 25141424 TI - What's the care point campaign all about? PMID- 25141425 TI - Make time for nothing. PMID- 25141426 TI - Justice conundrum. PMID- 25141427 TI - Nurses must speak up for democracy. PMID- 25141428 TI - Gerentology: recognising the team. PMID- 25141429 TI - Enrolled nursing: workforce issues. PMID- 25141430 TI - Perioperative conference: online programme released. PMID- 25141431 TI - International research: sustaining the profession. PMID- 25141432 TI - Heart failure: exploring the differences on the registry. PMID- 25141433 TI - Aged care: slow progress. PMID- 25141434 TI - Primary health care: bargaining starts. PMID- 25141435 TI - Private hospitals: three new collective agreements. PMID- 25141436 TI - Defining accountable care in the age of ACOs. PMID- 25141437 TI - Getting a visual on health analytics. PMID- 25141438 TI - Pharmacy chains continue to blur the line. PMID- 25141439 TI - Fraud detector. PMID- 25141440 TI - A sustainable mission: Gundersen nears total energy independence. PMID- 25141442 TI - Health care robotics. PMID- 25141441 TI - Planning for disaster. PMID- 25141443 TI - Improving project efficiency. PMID- 25141444 TI - Performance-based finishes. PMID- 25141446 TI - Leading your hospital to sustainability. PMID- 25141445 TI - Treating medical waste. PMID- 25141447 TI - More than 40 years of change in ES. PMID- 25141448 TI - Patient-centered construction. PMID- 25141449 TI - NASN and school nurses--a plan to grow. PMID- 25141450 TI - Diabetes and youth resources for school nurses: an update from the National Diabetes Education Program. AB - In response to the challenge of diabetes in youth, the National Diabetes Education Program (NDEP) has developed free, evidence-based education materials and online resources for school nurses, parents, and children living with or at risk for diabetes. This article highlights some of NDEP's resources and identifies ways for school nurses to use them with students and their families. PMID- 25141451 TI - The healthy school nurse: American Nurses Association's five constructs. PMID- 25141452 TI - A school nurse's guide to PowerPoint presentations. AB - In today's educational environment, school nurses are often called upon to provide presentations utilizing electronic slides. A tool frequently utilized for presentations is PowerPoint. However, as with any instructional method, it is only as effective as the presenter who has designed the slides. A study conducted to evaluate professional PowerPoint slides is the focus of this article. After reviewing 1,732 slides and comparing them to best practices criteria, the researchers call attention to common errors in slide presentations. Additionally, the article provides guidance to school nurses in reinventing the art of providing powerful, interactive, and interesting presentations. PMID- 25141453 TI - NASN connecting with nurses every day. AB - NASN, with a newly adopted strategic plan, is energized, committed, and positioned to be the connecting point for all things concerning school health. The July issue of the NASN School Nurse is utilized to provide an update to our membership on the health of our organization and the past year's major initiatives. The 2014-201 7 strategic plan has five areas of emphasis: membership, advocacy, financial stability, research, and governance. The purpose of this article is to discuss NASN's member resources and connections and how they can be utilized to strengthen and mold school nursing practice. PMID- 25141454 TI - Standardized data set for school health services: Part 1--getting to big data. AB - School nurses collect voluminous amounts of data in a variety of ways and use the data to describe trends in students' health and patterns of illness in the student population or to identify ways to improve care. NASN identified years ago that a national school nurse data set was needed to enable data-driven decision making for the millions of children who attend school each day across the United States. Informal work has been done in the past 5 years in preparation for the current joint NASN/ National Association of State School Nurse Consultants workgroup. This article is the first of a two-part series related to the importance of data and national efforts to develop a uniform data set that all school nurses can collect. Collecting data, and collecting it in the same way as other providers, will demonstrate what school nurses do as well as provide the data necessary for robust research on the impact of school nurses on students' health. PMID- 25141455 TI - Standardized dataset health services: Part 2--top to bottom. AB - It is critical for school nurses to promote and educate others on what they do. Data can help shape the message into understandable language across education and health. While Part 1 of this article discusses NASN's progress on identifying a standardized dataset for school health services, Part 2 focuses on the analysis and sharing of data at the local level. Examples of how to use the data to improve practice and create change are included. Guidance is provided in creating and sharing data as part of an annual report as a final step in advocating for school health services commensurate with student health needs. As the work on an evidence-based uniform dataset continues at the national level, what should be the response at the local level? Do we wait, or do we continue to collect certain data? The purpose of Part 2 of this article is to describe how data being collected locally illustrate health trends, benchmarking, and school nursing outcomes and can be compiled and shared in an annual report. PMID- 25141456 TI - Sports-related head injuries in students: parents' knowledge, attitudes, and perceptions. AB - The short- and long-term neurologic impairment of children sustaining sports related head injuries has recently entered the forefront of medical literature, resulting in new guidelines on concussion management being provided to clinicians, coaches, and trainers. Yet, most parents have not been formally educated on head injuries. The purpose of this article is to share the findings of a study conducted with 235 parents that identified their knowledge, attitudes, and perceptions of sports-related head injuries in school-age students. The study found that 51% of respondents were unaware that head trauma was more serious in children, 80% were uninformed as to whether the school district had a policy on sports-related head injuries, 44% did not know if there were medical guidelines for return to play, and 35% did not know that repeated head trauma could cause dementia. Results of this research implore school nurses to improve patient and parental education when they care for and monitor students with head injuries. PMID- 25141457 TI - School nursing services data: standardized documentation, collection, and utilization joint resolution. PMID- 25141458 TI - School nurse role in electronic school health records: position statement. PMID- 25141460 TI - Self-reported information sources and perceived knowledge in individuals with lymphedema. AB - Currently, a limited number of studies have been conducted that examine sources of information and knowledge level in individuals with lymphedema. This study aimed (1) to examine self-reported information sources and perceived lymphedema knowledge among individuals with lymphedema; and (2) to examine differences in self-reported information sources and perceived lymphedema knowledge among individuals with primary or secondary lymphedema; and with upper or lower extremity lymphedema. The National Lymphedema Network (NLN) conducted a survey to collect self-report data from March 2006 to January 2010. Overall, participants preferred a variety of sources of information. Participants reported low levels of knowledge about the types of lymphedema, treatment approaches and methods, and self-administrated therapies. In comparison to participants with secondary or upper extremity lymphedema, participants with primary or lower extremity lymphedema reported lower knowledge level regarding causes of lymphedema, risks for and complications of lymphedema, treatment approaches and methods for lymphedema, and self-administered therapies. Opportunities exist to expand lymphedema information sources. Healthcare professionals should focus on delivering high quality information about treatment and self-care management to individuals with lymphedema. PMID- 25141459 TI - Hyaluronidase treatment of acute lymphedema in a mouse tail model. AB - The purpose of this study was to investigate the impact of hyaluronidase (HAase) on lymphedema using an acute mouse tail lymphedema model. Six-week-old mice served to produce acute lymphedema and were then either treated with HAase injection or used as operative controls. An additional group of unmanipulated normal mice was used for comparison. Tail volumes were measured for 23 days and histological changes examined. Western blot analysis was conducted to quantify lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, podoplanin, CD 44, and vascular endothelial growth factor receptor3 (VEGFR3) expression levels. The operative control group showed an increase in thickness of the dermis and subdermis, microlymphatic dilatation, and an increase in neutrophils. In contrast, the HAase treated group exhibited alleviation of inflammation evidenced by a decline in microlymphatic dilatation and neutrophils and an overall increase in microlymphatic vessels. Western blot analysis demonstrated that TNF-alpha and TGF-beta1 expression declined but CD44 expression increased in the HAase treated group. Levels of LYVE1, podoplanin, and VEGFR3 also increased significantly in the HAase group. Our results indicate that HAase treatment in the acute mouse tail model reduced lymphedema volume possibly through degradation of HA trafficking, which reduced inflammation and fibrosis in tissues and stimulated lymphangiogenesis. PMID- 25141461 TI - The use of bioimpedance spectroscopy to monitor therapeutic intervention in patients treated for breast cancer related lymphedema. AB - We performed a multi-institutional analysis to evaluate the ability of bioimpedance spectroscopy (BIS) to capture the impact of lymphedema treatment compared with observation alone in the management of breast cancer related lymphedema (BCRL). We utilized a retrospective review of 50 patients with breast cancer who were evaluated with BIS at baseline and following loco-regional treatment. An analysis was performed comparing changes in L-Dex scores for those patients undergoing treatment for BCRL (n=13) versus those not undergoing intervention (n=37). A second (subset) analysis was also performed on all patients with elevated L-Dex scores compared to baseline prior to undergoing loco regional treatment (n=32). When comparing the cohort treated for BCRL to those not treated, L-Dex scores were significantly reduced (-4.3 v. 0.1, p=0.005) in the period following intervention (for treated patients). For the subset of patients with elevated L-Dex scores postoperation, the change in L-Dex score following BCRL treatment was significantly reduced (-5.8 v. 0.1, p=0.001) compared with the group observed that had elevated postsurgical L-Dex scores. In this analysis, BIS was able to detect early onset lymphedema and subsequently significant changes (reductions) in L-Dex scores directly related to intervention for BCRL compared with observation alone. PMID- 25141462 TI - Structural relationship between microlymphatic and microvascullar blood vessels in the rabbit ventricular myocardium. AB - We investigated the distribution and relationship between draining lymphatic vessels, lymphatic capillaries, and microvascular blood vessels in rabbit ventricular tissue. The left and right ventricular tissue from 15 healthy adult rabbits was obtained, processed, and sectioned for analysis. 5'-nucleotidase alkaline phosphatase (5'-Nase-Alpase) double staining was first used to identify lymphatic and blood vessels. Dual fluorescent immunohistochemical technique was then utilized with lymphatic endothelial cell marker podoplanin and blood vascular marker PAL-E. In addition, five ventricular samples were examined for ultrastructure using transmission electron microscopy (TEM). Draining lymphatic vessels and both lymphatic and blood capillaries were observed in the ventricular tissue. The lumens of draining lymphatic vessels were larger and irregular while the lymphatic capillaries were small in diameter and abundant. All lymphatic vessels were located among blood capillaries in the myocardium and aligned with the longitudinal axis of myocardial cells. The immunofluorescence double staining demonstrated that draining lymphatic vessels, lymphatic capillaries, and microvascular blood vessels were adjacent to each other and the cardiac myocyte with a ratio of lymphatic to microvascular blood vessels of approximately 1:1. This study suggests that lymphatic and blood capillaries exist in abundance and in nearly identical numbers in the ventricular myocardium and that they interweave with each other to comprise a complicated vessel network. PMID- 25141463 TI - Magnetic resonance lymphography (MRL): point and counter-point. AB - Two preeminent lymphologists debate the findings, implications, interpretations, and value of magnetic resonance lymphography (MRL) in the evaluation of peripheral lymphedema. Their contrasting views are discussed in the context of different lymphatic imaging modalities including MRL, lymphoscintigraphy, and microscopic anatomy. PMID- 25141464 TI - International Society of Lymphology General Assembly meeting minutes. PMID- 25141465 TI - The complex world of achieving quality. PMID- 25141467 TI - Slowing down the spiral toward kidney failure. PMID- 25141466 TI - Part 1: the status and health of state kidney programs. PMID- 25141468 TI - Expanding your nutritional knowledge. PMID- 25141469 TI - Fistula first offers new tools to improve outcomes. PMID- 25141470 TI - Part 2: community-based hospital systems: managing the costs of a dialysis program under the paradigm of affordable health care. PMID- 25141471 TI - 20th annual ranking: a look back, and getting positioned for the future. PMID- 25141472 TI - The name game: twenty years of dialysis provider history. PMID- 25141473 TI - What makes a happy, healthy physician? PMID- 25141474 TI - High school wrestling tournament decision making. AB - OBJECTIVE: This study is designed to aid in safe coverage of a large scale wrestling tournament and to provide information transferable to other sporting tournaments. BACKGROUND: Catastrophic injuries dominate the concerns of the medical teams covering sporting events. Insights gained from years of experience by the same medical team for one of the premier high school wrestling tournaments offers practical knowledge for successful preparation of a large scale event. Necessary personnel, equipment, and supplies are critical. DIFFERENTIAL DIAGNOSIS: Skin conditions and injuries sustained while wrestling MEASUREMENTS: Event preparation was performed by the same medical staff for three years, 2006, 2008 and 2009. Skin checks were performed on over 750 wrestlers each year. Disqualifications for untreated or under treated conditions were made as necessary. Approximately 1,700 bouts a year were supervised by the medical personnel. All injuries sustained were recorded by the medical staff and necessary disqualifications were made. FINDINGS: Each year wrestlers presented with the appropriate skin forms. Only in 2009, did a wrestler not have adequate treatment for MRSA impetigo and was disqualified. There were no catastrophic injuries in the recorded years. Medical disqualifications were also infrequent. In 2006, 2008 and 2009, 6, 17, and 8 disqualifications occurred respectively. The most common type of injury each year was a sprain/strain. CONCLUSION: Many clinicians are fearful of leading the medical staff for tournaments of such size. The presented recommendations provide an understanding and categorical check list of necessary staffing, logistics, equipment, and supplies. Preparation for known sports specific anticipated injuries and return to play decision making should help, but only successful completion of the event will provide the necessary confidence. PMID- 25141475 TI - Intracranial venous drainage through spinal veins. AB - There is extensive collateral networking at the craniocervical junction with a substantial anatomical and functional continuity between the veins, venous sinuses, and venous plexuses of the brain and spine. The predominant pathway for intracranial blood outflow may depend on the level and degree of obstruction. We are presenting an unusual case of predominant egress of intracranial blood through enlarged spinal canal venous collaterals due to thrombosis of the intracranial venous sinuses. Awareness of this unique pattern of venous drainage of the cranium is important and should be considered in the differential diagnosis of spinal arteriovenous malformation (AVM) or arteriovenous fistula (AVF). Magnetic Resonance Venography (MRV) of the brain should be considered to exclude intracranial thrombosis in these cases. PMID- 25141476 TI - Patient hand-offs. PMID- 25141477 TI - He's watching you. PMID- 25141478 TI - National Dental Practice-Based Research Network: A practitioner's update from the northeast region. PMID- 25141479 TI - Oral health & HIV disease: A New Jersey perspective. PMID- 25141480 TI - Correction to oral pathology quiz #82 from the Winter 2014 issue of Journal of NJDA. PMID- 25141481 TI - Oral pathology quiz #83 Case number 1. Retrocuspid papilla of the mandible or B. Hirschfeld's papilla. PMID- 25141482 TI - Oral pathology quiz #83 Case Number 2. Pyogenic granuloma. PMID- 25141483 TI - Oral Pathology Quiz #83. Case number 3. Odontogenic keratocyst. PMID- 25141484 TI - Oral Pathology Quiz #83. Case number 4. Ameloblastoma. PMID- 25141485 TI - Cocaine-induced palatal perforation: A case report. PMID- 25141486 TI - TobaccoNo dental initiative. PMID- 25141487 TI - Referred pain. AB - Comprehending orofacial referred pain requires an understanding of the neuroanatomy of the trigeminal nerve and associated cranial nerves. It also requires knowledge of the concept of neuronal convergence as well as the recognition that the caudalis is laminated and is therefore responsible for sensory receptive fields-that one interneuron may receive multiple sensory inputs and that structures within a lamina have sensory neurons which project into the caudalis and may share the same interneuron. PMID- 25141488 TI - Value of urinary survivin as a diagnostic marker in bladder cancer. AB - OBJECTIVE: To study the value of urinary survivin as a diagnostic marker for diagnosis of bladder cancer as compared to urine cytology. STUDY DESIGN: This study was carried out on 40 patients presenting with bladder cancer and 20 patients presenting with benign urological disorders. RESULTS: For bladder cancer diagnosis, urine cytology has lower sensitivity, accuracy, and negative predictive values as compared to survivin, while it has higher specificity and positive predictive value than survivin. On the other hand, the sensitivity, specificity, and the accuracy of combined survivin and urine cytology were 100%, 95% and 97%, respectively. Positive urine cytology and survivin were significantly higher in cases showing advanced stage and high grade as compared to cases presented with superficial stage and low grade. CONCLUSION: Urinary survivin appears to be a reliable, noninvasive diagnostic test to identify patients with bladder cancer. The sensitivity of survivin test was superior to that of urine cytology in the diagnosis of bladder cancer, especially in cases presenting with superficial stage or low grade. Combined evaluation of both survivin and urine cytology gave better sensitivity, specificity, and accuracy for bladder cancer diagnosis. PMID- 25141489 TI - Immunohistochemical detection of RET proto-oncogene product in tumoral and nontumoral mucosae of gastric cancer. AB - OBJECTIVE: To detect RET (REarranged during Transfection) protein by immunohistochemistry (IHC) in gastric cancer. STUDY DESIGN: A total of 210 samples were employed, of which 197 specimens were from 91 surgical pieces of gastric adenocarcinoma, comprising 91 tumoral, 91 nontumoral, and 15 intramucosal dysplastic samples. Another 13 gastric mucosae were from cancer-free patients. Two RET antibodies (clones Ret01 and 3F8) were used separately for IHC. RESULTS: Of the nontumoral samples from gastric cancers, 28 were positive (31%) with either antibody Ret01 or 3F8. The positive stains were often located in deep pyloric glands and associated with chronic inflammation patterns (p = 0.045). RET positivity correlated with phosphorylated epidermal growth factor receptor, which had been previously tested (p = 0.021). In tumoral samples RET was positive in 7 cases with antibody Ret01 (8%) and 9 cases with 3F8 (10%). In 15 intramucosal dysplastic samples RET was detected in 6 cases with antibody Ret01 and 8 cases with 3F8. There was an accordance between the IHC using antibodies Ret01 and 3F8 in tumoral, nontumoral, and intramucosal dysplastic samples (p = 0.500, 1.000, and 0.500). The 13 samples from cancer-free patients were always negative. CONCLUSION: Activation of RET proto-oncogene may be one of the molecular pathogeneses in gastric inflammatory and tumoral diseases. PMID- 25141490 TI - Predictive value of computerized morphometric analysis of steatosis in donor livers. AB - OBJECTIVE: To describe, by computerized morphometry, the degree and the type of steatosis in liver transplants that developed primary nonfunction and to compare the results with the quantification by pathologist. STUDY DESIGN: Twelve patients who developed primary nonfunction after liver transplantation were matched with 23 transplanted patients with a regular postoperative clinical course. Morphology of the liver biopsy included many stereological parameters; all cases were evaluated by an operator blinded to the diagnosis and to the clinical history. The assessment of steatosis by morphometry was compared with the pathologist's evaluation. Moreover, to assess the reproducibility of the morphometric model, another operator applied the morphometric model in a blinded fashion to a randomly selected sample of cases. RESULTS: The percentage of hepatocytes with microsteatosis and the ratio of macro/microsteatosis were higher in primary nonfunction. The pathologist's evaluation of steatosis showed a marked overestimation when compared to morphometry. Lastly, the comparison between the results of 2 blinded operators of morphometric analysis showed a high reproducibility with a low interobserver variability. CONCLUSION: Our quantitative estimation of the degree and the quality of steatosis avoids interobserver interpretations. Moreover, our analysis shows that the quantification of steatosis in liver transplantation by the current assessment must be reviewed in order to reevaluate the real impact of steatosis. PMID- 25141491 TI - Computer approach to recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma. AB - OBJECTIVE: To present a computerized system for recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma on the basis of microscopic images of the neoplasm cells in application of hematoxylin and eosin staining. STUDY DESIGN: The applied methods use combined gradient and mathematical morphology to obtain nuclei and classifiers in the form of support vector machine to estimate their Fuhrman grade. The starting point is a microscopic kidney image, which is subject to the advanced methods of preprocessing, leading finally to estimation of Fuhrman grade of cells and the whole analyzed image. RESULTS: The results of the numerical experiments have shown that the proposed nuclei descriptors based on different principles of generation are well connected with the Fuhrman grade. These descriptors have been used as the diagnostic features forming the inputs to the classifier, which performs the final recognition of the cells. The average discrepancy rate between the score of our system and the human expert results, estimated on the basis of over 3,000 nuclei, is below 10%. CONCLUSION: The obtained results have shown that the system is able to recognize 4 Fuhrman grades of the cells with high statistical accuracy and agreement with different expert scores. This result gives a good perspective to apply the system for supporting and accelerating the research of kidney cancer. PMID- 25141492 TI - Autonomic innervation of the periglomerular arteries. AB - OBJECTIVE: To explore spatial and volume relations of the calcitonine gene related peptide (CGRP)-positive and tyrosine hydroxylase (TH)-positive nerve fibers in the wall of cortical blood vessels. STUDY DESIGN: Kidney specimens from 10 rats were processed for confocal microscopy. Nerve fibers were stained with anti-CGRP and anti-TH antibodies and image stacks were collected. Three dimensional reconstruction and quantification of labeled fibers were performed to reveal their distribution and spatial relations. RESULTS: CGRP- and TH immunoreactive nerve fibers were distributed throughout the kidney cortex. TH positive fibers were dominant in the small periglomerular arteries (up to 4.6 fold). Examined nerves were finely intertwined in the wall of small blood vessels of the kidney and ran in the same nerve bundle but without co-localization. Extensive, web-like branching and varicosities of the TH nerves were observed. Sensory fibers prevailed in the wall of the larger arteries "embedded" into tubules near the medullary rays, and their endings can be verified in the muscularis layer of the interlobular arteries. CONCLUSION: Characteristics of the investigated fibers emphasize their role in the regulation of kidney blood vessel diameter and their influence on hypertension onset. PMID- 25141493 TI - Fungal prostatitis: an update. AB - Prostate pathology is a daily occurrence in urological and general medical consultations. Besides hyperplasia and neoplastic pathology, other processes, such as infectious ones, are also documented. Their etiology is diverse and varied. Within the infectious prostatic processes, fungi can also be a specific cause of prostatitis. Fungal prostatitis often appears in patients with impaired immunity and can also be rarely found in healthy patients. It can result from a disseminated infection, but it can also be localized. Fungal prostatitis is a nonspecific and harmless process. Diagnosis is commonly made by fine needle aspiration cytology or by biopsy. A number of fungi can be involved. Although there are not many reported cases, they are becoming more frequent, in particular in patients with some degree of immunodeficiency or those who live in areas where specific fungi are endemic or in visitors of those areas. We present a comprehensive review of the various forms of fungal prostatitis, and we describe the morphological characteristics of the fungi more frequently reported as causes of fungal prostatitis. We also report our own experience, aiming to alert physicians, urologists and pathologists of these particular infections. PMID- 25141494 TI - Therapy-resistant metastasizing anaplastic spermatocytic seminoma: a cytogenetic hybrid: a case report. AB - BACKGROUND: Anaplastic spermatocytic seminoma is a rare variant of the conventional spermatocytic seminoma, with only 6 cases reported up to now. The anaplastic variant contains only the medium-sized cell type, hallmarked by large sized nucleoli, whereas the small lymphocyte-like and giant cells typical of the conventional spermatocytic seminoma are lacking. CASE: We report herein an unusual case of a 40-year-old man with an anaplastic spermatocytic seminoma which metastasized first to the retroperitoneal lymph nodes and, something never before reported, subsequently to the lung and other organs. The immunophenotype with c kit and SALL4 positive and PLAP, as well OCT 3/4 negative tumor cells were identical to those of conventional spermatocytic seminoma. Cytogenetically the tumor cells showed a gain of chromosome 9, typical for spermatocytic seminoma, but simultaneously also the short arm 12p were overexpressed--an overexpression crucial to the aggressive behavior of seminomas and other nonseminomatous tumors but never before encountered in spermatocytic seminoma. CONCLUSION: The current opinion is that seminoma and nonseminomatous germ cell tumors develop from a common primitive progenitor cell, whereas spermatocytic seminomas develop from differentiated spermatogonia. The herein presented cytogenetic hybrid tumor shows that a crossover between the two different histogenetic "tracks" is possible. PMID- 25141495 TI - Experts advise hospitals to heed warning signs, leverage security to prepare against shootings. AB - While hospital shootings are not commonplace, studies suggest they are happening with increasing frequency, and that EDs are particularly vulnerable to this type of violence. Researchers report that roughly a third of all hospital shootings occur in the emergency setting. Experts say such incidents are typically targeted events, not random acts. Consequently, effective security programs should emphasize preventive steps to defuse potentially volatile situations and prevent weapons from entering the facility. Hospital security departments should be equipped to provide training to employees throughout the facility so that employees know how to respond if an active shooter is identified. Researchers report that between 2000 and 2012 there were 154 shootings in American hospitals, and that the frequency of these events increased markedly in the later years of the study. Experts say hospital shootings may involve disgruntled patients, dementia patients, or psychiatric patients, but the most common perpetrators are prisoners who are brought into the hospital for treatment under guard. Security experts say effective safety plans should focus on identifying threatening language or other signs of agitation early on so that interventions can be employed. They also advise hospitals to install gun lockers at every entrance point so that lawful weapons can be stored before owners enter the facility. Liberalized gun laws in some regions are making security more difficult at public hospitals. Also, hospitals need to be careful with surveillance activities that could raise privacy concerns. PMID- 25141496 TI - Use education to get staff on board with a team-approach to care. AB - Immediate bedding and the practice of swarming--delivering patient care as a team -can significantly slash wait times and overall length-of-stay in the ED. However, getting physicians and nurses to transition to such approaches is challenging because they must work at a higher pace than they are used to. Veterans of these approaches from Henrico Doctor's Hospital in Richmond, VA advise ED administrators to think through how these approaches would work in their own settings and obtain staff buy-in prior to implementation. Swarming typically requires repeated practice before it gels. Assigning personalities that work well together to the same team on a consistent basis may enhance effectiveness. Explain to staff that the transition to a swarming approach will be hard, but it will deliver dividends over the long term. Make contingency plans for days when the ED is short-staffed or volume is unusually high. Swarming does not work well in departments that are under-staffed. Consider the creation of an "expeditor" position. This is a veteran nurse who has the skills and experience to float wherever she is needed in the ED. PMID- 25141497 TI - A mid-year check-up on compliance and revenue. PMID- 25141498 TI - Practice recommendations cite use of disinfection caps, implementation strategies to reduce CLABSIs. AB - The use of disinfection caps is one strategy highlighted in updated guidelines that focus on reducing central line-associated bloodstream infections (CLABSI). The recommendations, which are sponsored by the Arlington, VA-based Society for Healthcare Epidemiology of America (SHEA) and other infection control organizations, focus not just on specific strategies, but also how to implement the strategies. Infection control advocates are hopeful that the dramatic gains made in reducing the incidence of CLABSls in ICUs can be extended to other units of the hospital setting including the ED. Disinfection caps are recommended under the"special approaches" section of the guidelines, which offers recommendations for locations or populations that have unacceptably high CLABSI rates. However, some hospitals are adopting the approach throughout their facilities with impressive results. Infection preventionists at Loyola University Medical Center in Maywood, IL report that disinfection caps helped them reduce CLABSls by 68% in one year, saving the organization more than $1 million. The approach replaces a scrub-the-hub approach that was used previously, but left room for error, according to administrators. Guideline authors gave disinfection caps a level 1 ranking, indicating that there is high-quality evidence to support their effectiveness. However, the authors stopped short of calling for their use on a routine basis PMID- 25141499 TI - EHR improvement needed to support medication reconciliation. PMID- 25141500 TI - [The Aldi principle]. PMID- 25141501 TI - [Globalization, cost effective - good?]. PMID- 25141502 TI - [Accompanying patients with the heart]. PMID- 25141503 TI - [Competent for an emergency]. PMID- 25141504 TI - [Recognizing malnutrition in the clinical routine]. PMID- 25141505 TI - [Students bring a fresh perspective to the professional association]. PMID- 25141506 TI - [Counterfeit drugs are everyone's business]. PMID- 25141507 TI - [Congress attendance as a learning experience]. PMID- 25141508 TI - [Giving a sense of trust back to the people]. PMID- 25141509 TI - [Recognizing and managing changes early]. PMID- 25141510 TI - [Blind trusting, blind writing]. PMID- 25141511 TI - [Health care far away]. PMID- 25141512 TI - [Childbirth in the Philippines]. PMID- 25141513 TI - ["Co-patient", "partner-co-producer" or "expert"?]. PMID- 25141514 TI - [Dying in a "place of life"]. PMID- 25141515 TI - [With the elan of vital forces]. PMID- 25141516 TI - [Diagnosis: ecological delirium]. PMID- 25141517 TI - [From Thomas Mann to doctor Shetty]. PMID- 25141518 TI - Inter- and intra-rater reliability of postural assessment for scoliosis. AB - OBJECTIVE: The purpose of the present study is to assess the inter- and intra rater reliability of a postural assessment for detecting scoliosis between 4th year physical therapy (PT) students and PT specialists by using 30 postural indices. MATERIAL AND METHOD: Six examiners, three 4th year PT students and 3 certified PTspecialists, performed the postural indices on 10 asymptomatic subjects. RESULTS: Inter-rater reliability between 4th year students and PT specialists and intra-rater reliability ranged from poor to almost perfect. Two items that needed rectification were PSIS level and iliac crest. CONCLUSION: There was a variable range of values in agreement either within or between examiners for the assessment of scoliosis screening. This shows that the assessment in scoliosis screening should be used with caution by 4th year students. PMID- 25141519 TI - Metabolic equivalent of exercise stress test explained by six-minute walk test in post coronary artery bypass graft and post percutaneous coronary intervention patients. AB - OBJECTIVE: To investigate the relationship among metabolic equivalents of an exercise stress test (METs of EST), demographic parameters (age, body weight, height, BMI), peak oxygen consumption (VO(2) peak), and six-minute walk distances (6MWD) determined from a six-minute walk test (6MWT). MATERIAL AND METHOD: Exercise capacity was estimated by a 6MWT and EST at the sixth week post operation in post coronary artery bypass graft (post CABG n = 17) and post percutaneous coronary intervention (post PCI, n = 13)patients. RESULTS: METs of EST showed: high correlation (p NKCT1 > Indomethacine treatment. The present study confirmed that GNP conjugation increased the antiarthritic activity and decreased toxicity profile of NKCT1. PMID- 25141539 TI - Suppression of Eis and expression of Wag31 and GroES in Mycobacterium tuberculosis cytosol under anaerobic culture conditions. AB - A major impediment in chemotherapy of Tuberculosis (TB) is the persistence of M. tuberculosis in a latent or dormant state, possibly perpetuated by paucity of oxygen within the lung granuloma. Proteome analysis of the anaerobically persisting microbe could therefore provide novel targets for drugs against latent TB infection (LTBI). An Indian clinical isolate of M. tuberculosis was cultured under aerobic and anaerobic conditions following Wayne's hypoxia model and its cytosolic proteins were resolved by two-dimensional gel electrophoresis (2DE). Peptide mass fingerprinting of 32 differentially expressed spots using MALDI TOF TOF MS-MS resulted in identification of 23 proteins. Under the anaerobic culture conditions, expression of 12 of these proteins was highly suppressed (>2 fold reduction in spot volumes), with 4 of them (GrpE, CanB, MoxR1 and Eis) appearing as completely suppressed since corresponding spots were not detectable in the anaerobic sample. On the other hand, 4 proteins were highly expressed, with two of them (Wag31 and GroES) being uniquely expressed under anaerobic conditions. Suppression of Eis could make the anaerobically persisting bacilli susceptible to the aminoglycoside antibiotics which are known to be acetylated and inactivated by Eis. Although all 4 overexpressed proteins can be considered as putative drug targets for LTBI, Wag31 appears particularly interesting in view of its role in the cell wall biogenesis. PMID- 25141540 TI - 43 kDa and 66 kDa, two blood stage antigens induce immune response in Plasmodium berghei malaria. AB - The hunt for an effective vaccine against malaria still continues. Several new target antigens as candidates for vaccine design are being explored and tested for their efficacy. In the present study the sera from mice immunized with 24,000 x g fraction of Plasmodium berghei has been used to identify highly immunogenic blood stage antigens. The protective antibodies present in immune sera were covalently immobilized on CNBr activated sepharose 4B and used for affinity chromatography purification of antigens present in blood stages of P. berghei. Two polypeptides of 66 and 43 kDa molecular weights proved to be highly immunogenic. They exhibited a strong humoral immune response in mice as evident by high titres in ELISA and IFA. Protective immunity by these two antigens was apparent by in vivo and in vitro studies. These two proteins could further be analysed and used as antigens in malaria vaccine design. PMID- 25141541 TI - Effects of magnesium on cytomorphology and enzyme activities in thyroid of rats. AB - Till date knowledge regarding the effects of high dietary magnesium on thyroid gland is incomprehensive though certain epidemiological studies reported development of thyroid gland dysfunctions in people with chronic exposure to hard water (especially with high magnesium) despite sufficient iodine consumption. The present study is to explore the effects of chronic high dietary magnesium exposure on thyroid morphology and functional status. Male adult albino Wistar strain rats were treated with graded doses of magnesium sulphate (MgSO4; 0.5, 1.0 and 1.5 g %) for 60 days and changes in different thyroid parameters were investigated. Significantly stimulated thyroid peroxidase and Na(+)-K(+)-ATPase and altered idothyronine 5'-deiodinase type I activities, enhanced serum thyroxine (T4) (both total and free), total triiodothyronine (T3) and thyroid stimulating hormone with decreased free T3 levels and T3/T4 ratio (T3:T4) along with enlargement of thyroid with associated histopathological changes were observed in the treated groups. The results clearly confirm that chronic high dietary magnesium exposure causes potential thyroid disruption as reported in earlier epidemiological studies. PMID- 25141542 TI - Evaluation of a novel decorporation approach to prevent radioactivity uptake by using acidosis in experimental animals. AB - With an aim to devise a prophylactic and/or therapeutic approach for preventing internalization of radiothallium (201Tl), and more importantly by implication, its chemical analogue radiocesium (137Cs) during any nuclear emergency, different ex vivo and in vivo animal models were created to determine the role ofpH in absorption of 201Tl across jejunum/muscle tissue and whole body retention of 201Tl respectively. Movement of Tl+ under simulated pH conditions proved that pH had direct influence on its absorption. Oral intake of acidified water or parenteral administration of lactic acid was able to reduce the body burden of 201Tl by up to 12 and 50% respectively. The results indicate that acidification of gut, within physiological range may be used as an option for decorporation/inhibition of incorporation of radiothallium and radiocesium, particularly in cases of mass casualty. PMID- 25141544 TI - Comparative immunomodulation potential of Tinospora cordifolia (Willd.) Miers ex Hook. F., Tinospora sinensis (Lour.) Merrill and Tinospora cordifolia growing on Azadirachta indica A. Juss. AB - Guduchi has been widely used in the traditional medicine as an immunomodulator. Description of guduchi in Ayurvedic literature resemble with T. sinensis rather than with commonly available T. cordifolia and hence this may be used as substitutes for T. sinensis. T. cordifolia growing on Azadirachta indica commonly called Neem-guduchi has more immunomodulatory potential. Thus, immunomodulatory activity of three Tinospora spp. was assessed by checking humoral and cell mediated immune responses to the antigenic challenges with sheep RBCs and by neutrophil adhesion tests on albino Wistar rats using Guduchi-Satwa, a well known dosage form. Results revealed that Neem-guduchi possesses higher immunomodulatory potential at the dose of 300 mg/kg, po and validated the traditional claim. Hence, Neem-Guduchi can be employed in immunomodulatory formulation prepared using guduchi. PMID- 25141543 TI - Punarnavine, an alkaloid isolated from ethanolic extract of Boerhaavia diffusa Linn. reverses depression-like behaviour in mice subjected to chronic unpredictable mild stress. AB - Punarnavine (20 and 40 mg/kg) and fluoxetine (20 mg/kg) per se administered orally for 14 successive days significantly decreased immobility periods of both unstressed and stressed mice in forced swim test. These drugs also significantly decreased sucrose preference in both stressed and unstressed mice as compared to their respective controls, indicating significant antidepressant-like activity. The drugs did not show any significant effect on locomotor activity of mice. The alkaloid also significantly decreased monoamine oxidase (MAO-A) activity, malondialdehyde levels in both unstressed and stressed mice; and significantly reversed the stress-induced decrease in reduced glutathione and catalase activity. It also significantly attenuated the stress-induced increase in plasma nitrite and corticosterone levels. Thus, punarnavine showed antidepressant-like activity in unstressed and stressed mice probably through inhibition of brain MAO A activity, decrease in plasma nitrite levels and due to its antioxidant activity. In addition, punarnavine also showed antidepressant-like activity in stressed mice possibly through decrease in plasma corticosterone levels. PMID- 25141545 TI - Effect of acute exposure of triazophos on oxidative stress and histopathological alterations in liver, kidney and brain of Wistar rats. AB - Acute dose of organophosphorus pesticide Triazophos (O,O-diethyl O-1-phenyl-1H 1,2,4-triazol-3-yl phosphorothioate; Tz) administered orally affects oxidative stress parameters and the histo-architecture of liver, kidney and brain tissues. The results indicate a dose dependent induction of oxidative stress as evident by increased malondialdehyde level and decreased antioxidant defense including glutathione and superoxide dismutase activity in rat liver, kidney and brain. AChE activity was found significantly decreased in the Tz treated groups as compared to the vehicle control (DMSO) group. Histopathological examination of liver, kidney and brain in Tz treated rats revealed medullary congestion and hydropic degeneration of hepatocytes in liver and medullary congestion in kidney. However, no significant histopathological changes were observed in brain tissues. PMID- 25141546 TI - A simple technique for tracking individual spore and gametophyte development in Adiantum lunulatum Burm. f. using modified extra thin alginate film technique. AB - A new technique was developed for accurate calculation of percent germination and tracking of individual spores from germination to gametophyte development in Adiantum lunulatum. High percentage of ETAF immobilized spore germination (72.4%) was followed by development of gametophytic clumps. The ETAF immobilized clumps were cut into pieces and multiplied en masse. Apomictic sporophytes developed from the gametophytes. This indicated the potential of ETAF for mass propagation of A. lunulatum without the need to start from spores. Since individual spores can be tracked from germination to gametophyte development, the ETAF technique has the potential to be used for (i) harvesting uniformly developed plants of similar age for extensive experimentations and commercial utilization and (ii) detailed study on developmental and reproductive biology of different ferns and fern allies. PMID- 25141547 TI - In vitro flowering--a system for tracking floral organ development in Dendrocalamus hamiltonii Nees et Arn. ex Munro. AB - Dendrocalamus hamiltonii plants are slender and tall (15-25 m) thereby, rendering tagging, sampling and tracking the development of flowers difficult. Therefore, a reproducible system of in vitro flowering was established for tracking the stages of flower development. MS medium supplemented with 2.22 microM 6 benzylaminopurine, 1.23 microM indole-3-butyric acid and 2% sucrose was optimized as the flower induction medium (FIM) wherein 28 and 42 days were required for the development of gynoecium and androecium, respectively. Six distinct stages of in vitro flower development were identified, and the flowers were comparable with that of in planta sporadic flowers. Pollen viability of the in vitro flowers was higher than those of in planta ones. The in vitro system developed in the present study facilitates easy tracking of different stages of flower development under controlled environmental conditions. It can also be used for medium- or long-term storage of pollens and manipulation of in vitro fertilization. PMID- 25141548 TI - Antiangiogenic and antiproliferative assessment of cyanobacteria. AB - Biologically active compounds with different modes of action, such as antiproliferative, antioxidant, antimicrotubule, have been isolated from algae and cyanobacteria. The present study was designed to evaluate antiangiogenic and antiproliferative potential of dichloromethane and methanol (2:1) extracts of different cyanobacteria. Further fingerprinting of the activity possessing extracts were carried out using ESI-LC-MS/MS. Extracts (25, 50 and 100 microg) were screened in the vascular endothelial growth factor (VEGF) induced angiogenesis in inovo chick chorioallontoic membrane assay (CAM) at various concentrations using thalidomide and normal saline as positive and untreated control groups respectively. The extracts were also evaluated for their antiproliferative activity by MTT assay using HeLa cancer cell line. The results obtained from the various algal extracts did not show any significant antiangiogenic activity as compared to VEGF control. Oscillatoria sp. and Lyngbya officinalis exhibited significant anti-proliferative activity at IC50 values of 220 and 260 microg/mL respectively. ESI-LC-MS/MS of L. officinalis showed the presence of lyngbyatoxin-A and that of Oscillatoria sp. reveals the presence of malyngamide-J suggesting the possibility of antiproliferative activity. PMID- 25141549 TI - Bionomics and vectorial capacity of Anopheles annularis with special reference to India: a review. AB - Anopheles annularis is widely distributed mosquito species all over the country. An. annularis has been incriminated as a malaria vector in India, Sri Lanka, Bangladesh, Myanmar, Indonesia, Malaysia and China. In India, it has been reported to play an important role in malaria transmission as a secondary vector in certain parts of Assam, West Bengal and U.P. In Odisha and some neighbouring countries such as Sri Lanka, Nepal and Myanmar it has been recognised as a primary vector of malaria. This is a species complex of two sibling species A and B but the role of these sibling species in malaria transmission is not clearly known. An. annularis is resistant to DDT and dieldrin/HCH and susceptible to malathion and synthetic pyrethorides in most of the parts of India. In view of rapid change in ecological conditions, further studies are required on the bionomics of An. annularis and its role in malaria transmission in other parts of the country. Considering the importance of An. annularis as a malaria vector, the bionomics and its role in malaria transmission has been reviewed in this paper. In this communication, an attempt has been made to review its bionomics and its role as malaria vector. An. annularis is a competent vector of malaria, thus, due attention should be paid for its control under the vector control programmes specially in border states where it is playing a primary role in malaria transmission. PMID- 25141550 TI - Effect of domiciliary limb hygiene alone on lymphoedema volume and locomotor function in filarial lymphoedema patients in Puducherry, India. AB - Lymphoedema of extremities is a major clinical manifestation of lymphatic filariasis. Recurrent episodes of acute dermato-lymphangioadenitis (ADLA) in these patients lead to progression of the clinical condition. Studies have documented the effectiveness of regular limb hygiene in reduction in frequency and duration of ADLA. However, no data is available on the effectiveness of limb hygiene alone on reduction of lymphoedema volume and locomotor function of the affected extremities. A total of 93 consecutive patients visiting VCRC Filaria Clinic formed a cohort for the study. The limb hygiene kit was supplied monthly free of cost to the patients. Assessments of oedema volume, frequency and duration of ADLA and quantitative assessment of locomotor function were carried out at baseline and after 12 months of intervention. All the 93 patients completed the follow-up. A total of 82 (88%) patients practiced limb hygiene regularly. The practice was higher among patients with higher grades of lymphoedema. The mean frequency of ADLA reduced from pre-intervention level of 2.4 to 0.8 during 12-month period of intervention in grade I cases, from 3.4 to 1.2 in grade II and from 4.8 to 1.8 in grade III cases. The mean duration (in days) for each ADLA episode was reduced from 4 at the rpe-intervention level and 2.5 during the 12-months intervention period. Though 'limb hygiene' practiced in domiciliary settings is feasible. Regular practices resulted in reduction of frequency and duration of ADLA attacks. However, reduction in oedema volume or improvement the locomotor function was not observed during 12 month period. PMID- 25141551 TI - HIV and TB co-infection in Indian context. AB - This study was carried out in a Anti-Retroviral Therapy Clinic and TB center of a tertiary level hospital to find out socio-demographic correlates of HIV/TB individuals and risk factors of HIV/TB co-infection in Indian context. It is a case-control study comprising 420 subjects, 3 groups of 140 each. For a case group of HIV-TB co-infected subjects, two control groups, one comprising HIV patients (not having TB), and the other TB patients (not having HIV). Majority 267 (63.6%) males, 100 (71.4%) in case group (HIV/ TB), 74 (52.9%) in control group 1 (TB) and 93 (66.4%) in control group 2 (HIV). Mean (+/-SD) age of case group was 34.91 (+/- 8.57) years. New TB cases were 213 (76.1%), more among control-group 1, compared to case-group. Multivariate analysis showed that risk of co-infection was 1.94 times higher among individuals aged >35 years. Difference statistically significant amongst those who were not on ART than who were on ART (p < 0.001). Those with CD4 counts <200 had 1.85 times risk of TB. Smokers had 1.92 times risk of TB. Co-infection higher in males, in age group 35 44 years, urban area, lower educational status and lower socioeconomic class. Current history of smoking significantly associated with co-infection. HIV status during TB infection was detected in 1/4th of study subjects. History of TB symptoms in family significantly associated with co-infection. PMID- 25141552 TI - A study to compare the effect of adding 12 days DEC regimen to 6 years annual mass drug administration to eliminate microfilaraemia infection in the community in rural Kanpur, Uttar Pradesh, India. AB - Lymphatic filariasis is a major public health problem of tropical countries. Although its elimination is planned as global effort using mass drug administration in affected communities but its impact has been influenced by MDA coverage across countries. The drug coverage is affected by fever as side effect and its continuation for over 6 years which affect the population participation. Therefore alternative approaches are needed which can show impact faster than standard MDA. Present research using additional 12 days dose of DEC to mf carriers, show that if drug coverage could be regular, sustainable impact could be created in 4 years. PMID- 25141553 TI - Antimicrobial resistance in bacterial isolates from a delhi hospital: one year outcomes. AB - Antimicrobial resistance and hospital acquired infections have become an important public health issue. Data on pathogen and antibiotic resistance is important for physicians, microbiologists and infection control officials but limited information on antibiotic resistance prevents pathogen specific therapy and propels antibiotic misuse. A retrospective review of bacterial isolation and antimicrobial susceptibility profiles in the in- and outpatients of a Delhi hospital between January 2009-December 2009 was performed. A total of 1772 pathogens causing bacterial infections were recorded during the study period January 2009-December 2009. The most frequently encountered bacterial pathogens were Escherichia coli (40.51%), Klebsiella spp. (14.84%) and Staphylococcus aureus (13.99%). We encountered high resistance to ciprofloxacin in Enterobactereaceae family, i.e., 32.5%. Aminoglycosides, once considered optimum for broad spectrum coverage of pathogens for almost all systemic infections, are now showing high rate of resistance as was noted in Acinetobacter sp. (57.14%) and Pseudomonas aeruginosa (69.2%). Antibiotic susceptibility results show a higher level of resistance to cotrimoxazole, cephalosporins and ciprofloxacin which are easily available, orally administered and cheaper and thus are considered a better option for the patients. This study provides insight into the problem of resistance in bacterial pathogens in Delhi. Our results demonstrated that, in general, isolates have high rates of resistance to antibiotics commonly used in developing countries. Guidelines for surveillance and prevention of nosocomial infections must be implemented in order to reduce the rate of hospital acquired infections. PMID- 25141554 TI - Awareness and practices regarding malaria in clinical suspects and the alarming slide positivity rate amongst them: a hospital based study from Delhi. AB - It has been repeatedly reported that lack of effective community participation in malaria control strategies has been partly responsible for high incidence of malaria in India. Active involvement of community in malaria control is a function of the awareness of that community. The present study was conceived with the objective to study the awareness and practices regarding malaria among fever cases clinically suspected of malaria and to assess the slide positivity rate among the same. Awareness and practices of 101 consecutive clinically suspected malaria cases (presenting with fever) attending medical OPD in Satyawadi Raja Harishchandra Hospital, Narela in North West district of Delhi regarding malaria were assessed using a 37 item pre-tested, semi-structured, semi-open ended, and Investigator administered questionnaire. Thin blood films were made for these patients and stained by Romanowski's method using Leishman's stain and reported by haematologist in the Department of Pathology, UCMS & GTB Hospital, Delhi. 37.5% patients had fever ranging from 1-3 days & 60% patients knew of chills and rigors as a symptom of malaria. While 80.2% patients correctly reported that malaria is caused by mosquito, only 52% patients stated that water should not be allowed to stagnate in order to prevent mosquito breeding. 61% patients did not get their houses sprayed with insecticides in last one year. 85.4% patients used one or more methods for personal protection against malaria. On laboratory examination 21% peripheral smears were found to be positive for Plasmodium vivax. Respondents were found to have modest knowledge regarding malaria. Relatively high malaria positivity was seen in malaria suspects. These aspects need to be addressed by the programme managers. PMID- 25141555 TI - Knowledge and practices about hospital waste disposal and universal safety precautions in class IV employee. AB - Norms and guidelines are formed for safe disposal of hospital waste but question is whether these guidelines are being followed and if so, to what extent. Hence, this study was conducted with objective to study the knowledge and practices about hospital waste disposal and universal safety precautions in class IV employee and to study its relationship with education, occupation and training. A cross-sectional study was carried out in a teaching hospital in Mumbai using semi structured questionnaire in which Class IV employee were included. Questionnaire was filled by face to face interview. Data were analyzed using SPSS. 48.7% Class IV employee were not trained. More than 40% were following correct practices about disinfection of infectious waste. None of the respondents were using protective footwear while handling hospital waste. Only 25.5% were vaccinated for hepatitis B. 16% had done HIV testing due to contact with blood, body fluid, needle stick injury. Knowledge and practices about hospital waste disposal and universal precaution were statistically significant in trained respondents. Training of employees should be given top priority; those already in service should be given on the job training at the earliest. PMID- 25141556 TI - Critical appraisal of mass DEC compliance in a district of west Bengal. AB - A cross sectional study was carried out to assess drug compliance after Mass Drug Administration of DEC and the factors responsible for poor compliance among the population of Murshidabad district of West Bengal during Jan 2009. Total study unit were 120 families covering 3 villages and one municipality ward area (30 families from each area). As a part of Revised Filaria control strategy, MDA programme was implemented in Murshidabad district from 29th-31st December 2008. Result revealed that total covered population were 601, out of which 571 were eligible population for Mass drug administration (6 Pregnant women and <2 years age groups (24) were excluded). Drug distribution rate was 91.8%. Overall drug compliance was 42.3%. Total number of defaulters was 330 (57.7%). Non compliance was highest (75.5%) in urban area. Defaulters was more among male than female. Factors responsible for defaulters were no motivation (24.7%), drugs not supplied (22.5%), absence at home (13.5%), no faith (10.1%), fear of side effects (10.1%) and others (Forgotten, lack of prior IEC etc), illness, wrong information were 7.8%, 7.3%, 3.9% respectively. Majority has no side effects, only dizziness (3.3%), headache (1.7%), vomiting and others (4.1%) were experienced by the people after consumption of drugs. On an average 40% families were aware about ELF & transmission of disease. Only 43.7% of community members were informed about MDA by Health Workers prior to the implementation of MDA programme. PMID- 25141557 TI - Study of mortality pattern in Coonoor urban area--a preliminary study. PMID- 25141558 TI - Challenges of communicable diseases during disasters. PMID- 25141559 TI - Human fascioliasis with biliary complications. AB - We report a case of human fascioliasis adding to the few of the previously reported cases in India. A young boy from rural background in Bihar presented with diarrhea, vomiting, hepatic tenderness, jaundice and fever along with peripheral eosinophilia. Examination of stool revealed yellow-brown eggs of Fasciola hepatica. Human fascioliasis should be kept in mind in patients with cholangitis and eosinophilia especially in areas of sporadic occurrence. PMID- 25141560 TI - Bacteraemic Haemophilus influenzae type B pneumonia complicated with empyema- report of a case and review of literature. AB - A case of bacteraemic pneumonia complicated with pleural empyema due to Haemophilus influenzae type b is reported in a one-year old previously healthy child who had apparently no other associated medical condition. The organism was isolated from both the pleural fluid aspirate and blood of the patient with pneumonia. She was successfully treated with parenteral ampicillin and chloramphenicol alongwith intercostal chest tube drainage. The case is notable because it adds to the existing disease spectrum of invasive Hib diseases and brings awareness to the existing burden of the disease in Asia. In addition, it reflects the urgent need to include Hib vaccine in the current immunization program in India. PMID- 25141562 TI - [Physical activity for children: a sensible balance]. PMID- 25141561 TI - Postnatally acquired dengue in a neonate--a case report. AB - Dengue was earlier a disease of children. But with increasing incidence in adults, dengue is increasingly encountered in infants and sometimes in neonates. The usual mode of transmission in neonates is vertical. We report a neonate with horizontal transmission of dengue. Dengue should be considered in the differential diagnosis of neonatal septicemia especially during dengue season even in the absence of maternal symptoms, to ensure proper case management. PMID- 25141563 TI - [Sport: practiced from birth?]. AB - Physical activity in children is on the decline, leaving room for sedentary behaviour. Children are mentally over stimulated through the use of screens, but their physical condition is diminishing. The benefits of physical activity in adults are well known. Although paediatric literature is less abundant, the benefits of regular physical activity in young children are real and extend into adulthood. The promotion of physical activity can be made by any responsible adult in a child's entourage. It means clarifying the confusion between physical activity and sport, evaluating the balance between the physical and sedentary behaviour of the children and their families and establishing with them the possible necessary changes. PAPRICA--young childhood is 4 hour interdisciplinary training session approaching these various themes. PMID- 25141564 TI - [Athletic pubalgia and hip impingement]. AB - Athletic pubalgia is a painful and complex syndrom encountered by athletes involved in pivoting and cutting sports such as hockey and soccer. To date, there is no real consensus on the criteria for a reliable diagnostic, the different investigations, and the appropriate therapy. Current literature underlines intrinsic and extrinsic factors contributing to athletic pubalgia. This review article reports upon two novelties related to the issue: the importance and efficience of prevention program and the association of femoro-acetabular impingement with the pubalgia. PMID- 25141565 TI - [Patellofemoral pain syndrome: understand better in order to treat better]. AB - Patellofemoral pain syndrome (PFPS) is one of the most frequent cause of anterior knee pain in adolescents and adults. Due to its complex etiology, which is multifactorial and still poorly understood, its management is a major challenge for the practitioner. The diagnosis is made primarily on the history and clinical examination of the knee, but also of the entire lower limb, which may sometimes require the completion of imaging. The treatment is mostly conservative, focussing on rehabilitation with targeted and personalized therapy. Surgical treatment is reserved for cases with a causal structural lesion. PMID- 25141566 TI - [Concussion and sport: too often underdiagnosed]. AB - Concussions are frequent in contact sports. Clinical symptoms, cognitive impairment, neurobehavioral features can be present. Loss of consciousness is rare. If suspicion, the player must be removed from the game. Return to play is gradual; it may be possible only if the sportsman is asymptomatic. Strict application of the rules of the game, fair play can decrease the incidence of concussion. SCAT (pocket, SCAT 3, SCAT Child) should be used as a help to diagnosis and follow up. PMID- 25141567 TI - [Concussion in children and adolescents during sports]. AB - Concussion, a frequent injury in sports, is rarely evoked and often trivialized in children and teenagers. Knowledge of the diverse symptoms and signs to seek for is essential to an appropriate and secure management. The initial treatment relies on cognitive and physical rest followed by a progressive return to school and subsequently sport activities. The aim of this article is to review an injury whose prognosis is generally favourable, but whose rare complications can prove dramatic. PMID- 25141569 TI - [How to promote a humanistic attitude and caring in patient care]. PMID- 25141568 TI - [Deleterious effects of smoking on the musculoskeletal system]. AB - Tobacco smoking has important negative effects on the musculoskeletal system: decrease of bone mineral density, increase of the risk of injury, illness, and perioperative complications such as fracture-healing complications and wound complications. Orthopaedic surgeons should inform all patients of the increased risks associated with active smoking in the perioperative period and should encourage them to quit smoking four to eight weeks in advance of the proposed procedure. PMID- 25141570 TI - [What about the contribution of genetics in prostate cancer screening?]. PMID- 25141571 TI - [Miscellaneous, July 2014]. PMID- 25141572 TI - [Physician intuition is the most important element for discovering a serious disease]. PMID- 25141573 TI - [Due to the internet, patients are more knowledgeable: this is a (bad) children's story]. PMID- 25141574 TI - [Emotional dependence]. PMID- 25141575 TI - Study of the influence of lipids on the balance parameters in patients with well and poorly controlled arterial hypertension. AB - STUDY AIM: To assess the correlation of the level of cholesterol fractions and balance in two groups of patients with well and poorly controlled hypertension. MATERIAL AND METHODS: The study included 106 patients: 41 males and 65 females with diagnosed arterial hypertension without concomitant diseases which could affect the balance system. The average age of the patients was 52.1 +/- 7.7 years. The values of the level of individual lipid fractions from the previous three months were obtained from the medical records of the patients. The influence of the cholesterol fractions in the patient group with well and poorly controlled hypertension on balance parameters was assessed. The balance examination was conducted on a stabilometric platform. RESULTS: The study results indicate a correlation between balance disorders and the increase of cholesterol levels in people with hypertension regardless of its level of control. Patients with uncontrolled hypertension more frequently presented a deterioration of the balance parameters examined on the stabilometric platform. The increase in the level of the LDL cholesterol fraction was associated with a deterioration of the balance parameters only in the group with uncontrolled hypertension, both in the eyes open and eyes closed test. The increase in the level of cholesterol and its individual fractions in combination with arterial pressure above 140/90 mmHg in our study deteriorated the balance parameters for the distance traveled, velocity of movement and the size of the area marked by the projection of the center of gravity in the examined persons. CONCLUSIONS: Disorders of lipid balance may be associated with changes in the balance system and accelerate their development in people under 60 years of age, which translates to worse balance parameters achieved in the stabilometric platform test, especially PMID- 25141576 TI - Homocysteine in patients with inflammatory bowel diseases. AB - BACKGROUND: Hyperhomocysteinemia seems to be a common phenomenon in both patients with ulcerative colitis and Crohn's disease. Many factors including deficiencies of cobalamin, folate and pyridoxine, smoking habits, alcohol and coffee intake, some medications and age may predispose subjects to hyperhomocysteinemia. The study aimed to evaluate homocysteine levels in an inflammatory bowel disease cohort as dependent of life style and disease activity. METHODS: 85 consecutive patients with inflammatory bowel disease (38 with Crohn's disease and 47 with ulcerative colitis) and 65 control subjects were included in the prospective study. The following parameters were analyzed: disease activity, duration of the disease, location of pathological changes, presence of complications, current medications, past surgical procedures, smoking history, concomitant diseases, biochemical parameters and plasma homocysteine levels. RESULTS: Mild hyperhomocysteinemia was found in 16 patients with Crohn's disease (42%), 19 patients with ulcerative colitis (40%) and 19 patients in the control group (29%) (p = 0.59). There was not any significant correlation between homocysteine level and disease activity. Only folic acid supplementation and gender affected homocysteine level. Folic acid intake led to reduction of homocysteine levels in all groups of patients (11.8 micromol/l vs. 8.33 miccromol/l, p = 0.0065 in Crohn's disease patients and 10.94 micromol/l vs. 7.78 micromol/l, p = 0.0069 in ulcerative colitis patients). CONCLUSION: Homocysteine level in patients with inflammatory bowel disease is mostly normal or slightly elevated. Disease activity does not have an impact on homocysteine level. Folic acid is the most important factor having an influence on homocysteine level in patients with inflammatory bowel disease. PMID- 25141577 TI - [Seizures--symptom or cause of stroke]. AB - The most frequent reason of seizures in elderly are vascular diseases of the brain. The early-onset seizures occur in first 7 days after stroke, and the late onset seizures occur after 7 days after stroke. The aim of the study was to estimate the frequency of seizures in patients who have taken a stand in acute period of stroke, the incidence of seizures in different types of stroke, the frequency of the types of seizures and the risk of death depending on the type of seizure. One hundred and sixty seven patients with ischemic stroke and seizures were enrolled in this retrospective study. Patients have been divided into 2 groups: group I-with early-onset seizures and group II- with late-onset seizures. In our study seizure was the first symptom of acute stroke in 2.4% of ischemic stroke and 3.2% among patients with cerebral hemorrhage. Seizures occurred in 3.9% of patients with PACI stroke. The primary tonic-clonic generalised seizures occurred in 46.7% patients with early-onset seizures. In the group with early onset seizures the mortality was 13.3%. In the group of poststroke epilepsy the mean time from stroke to seizure was 21 month. The early-onset seizures occurred in 2.5% patients with acute stroke. The early-onset seizures are most related to PACI stroke and cerebral hemorrhages. The primary tonic-clonic generalised seizures are most common in both groups. The highest mortality among early-onset seizures is related to primary tonic-clonic generalized and focal complex seizures. PMID- 25141578 TI - [Adherence to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis]. AB - A close collaboration between doctor and patient is essential for optimization of treatment outcomes in patients with chronic disease. Nonadherence to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may contribute to treatment failure and result in loss of joint function. The aim of the study was to evaluate adherence to prescribed drug therapy by patients with RA 6 months after hospital discharge. The influence of age, sex, level of education and DAS28 score on compliance with treatment regimen was also evaluated. MATERIALS AND METHODS. A telephone survey was conducted using a questionnaire. The survey involved 146 randomly selected patients who were previously treated at the Department of Rheumatology for worsening of rheumatoid arthritis. RESULTS: Most of the patients gave their consent for participation in the survey. 113 (82.5%) of the respondents reported good compliance /adherence with the DMARD treatment regimen. 24 (17.5%) of the patients did not take prescribed medications, primarily due to adverse side effects and, less commonly, due to ineffective treatment or lack of clinical symptoms, and also for financial reasons. Age, sex, level of education and DAS28 score did not significantly influence medication adherence. CONCLUSIONS: Most of the patients treated for RA are followed up at rheumatology outpatient clinics and they continue treatment with DMARDs after discharge from hospital. Adverse side effects are the main cause of a change or discontinuation of the treatment. PMID- 25141579 TI - [Endoscopic and histopathological findings of the upper gastrointestinal tract in patients with functional and organic dyspepsia]. AB - INTRODUCTION: Endoscopic examination of the upper gastrointestinal tract (upper GI) with macroscopic and histopathological evaluation provides essential tool to differentiate the organic and functional causes of dyspepsia. The distinction, however, is often smooth and not fully defined. The aim of this study was to assess the frequency and type of the macroscopic and histopathological changes in the upper GI endoscopy in patients with symptoms of dyspepsia. MATERIAL AND METHODS: A retrospective study was performed on 212 patients with dyspepsia, at the age of 18-84 years, including 60 patients to 45 years of age (group I) and 152 patients older than 45 (group II) who underwent gastroscopy. The severity of esophagitis was classified according to the Los Angeles Classification and gastritis according the updated Sydney system. Biopsy specimens were taken from the gastric and duodenum for histopathological examination. The presence of H. pylori infection has been established on the basis of histopathological examination and positive rapid urease test. RESULTS: Reflux esophagitis was found in 18 patients (8.5%), slightly more common in people over 45 years of age (group I--5%, group II--9.2%). The mild forms of esophagitis occurred most frequently. A more advanced form of inflammation and Barrett's esophagus was found only in patients over 45 years of age. Normal gastric and duodenal mucosa was revealed in 30% of patients in group I and 9.2% in group II. The most common endoscopic lesion was gastritis, mostly erythematous-exudative and less often atrophic. The presence of H. pylori infection was varied in the different types of inflammation. H. pylori infection occurred most frequently in the case of erosive and follicular gastropathy. The most common location of H. pylori infec- frequent in older patients. Peptic ulcer was found in 4.7% of patients (group I--5%, group II--4.6%). In one patient (61 years old) stomach cancer was diagnosed and in one patient (<45 years old) Crohn's disease of the upper GI was diagnosed. The majority of patients had normal duodenal mucosa. In 3.3% of patients (group I- 8.3%, group II--1.3%), who had not previously diagnosed celiac disease, histopathological changes typical of celiac disease has been shown. In all patients, in whom biopsy specimens were taken from normal duodenal mucosa (14% of patients), histopathological examination revealed the presence of non-specific inflammation, regardless of the coexistence of H. pylori infection. CONCLUSION: Regardless of the severity of lesions of the upper GI endoscopy in patients with dyspepsia, it is advisable to take biopsy from the gastric and duodenal mucosa, which allows for an individualized management of these patients. Celiac disease should be considered in the diagnosis of the causes of dyspepsia. Further studies of microscopic duodenitis in patients with dyspepsia are needed. PMID- 25141580 TI - Oncological emergencies: tumor lysis syndrome. AB - Tumor lysis syndrome (TLS) occurs as a result of massive lysis of malignant cells and release of intracellular contents into the systemic circulation. It can lead to hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia. TLS is most commonly present after initiation of anticancer therapy but it can also develop spontaneously (STLS--spontaneous tumor lysis syndrome). In the article, pathophysiology, classification, risk factors and recommendations of management in TLS, with a special focus on solid tumors, are discussed. The keys to the identification of high-risk patients, prevention and management of TLS are included in presented guidelines. PMID- 25141581 TI - [Pharmacological treatment of behavioral symptoms in dementia patients]. AB - Cognitive manifestations usually are the primary abnormalities in dementia. In most cases cognitive deterioration arise in association with behavioral disturbances, and may accelerate institutionalization of patients. Noncognitive symptoms are distressing for both patients and their caregivers. These symptoms are described as "behavioral and psychological symptoms of dementia--BPSD" or neuropsychiatric symptoms. BPSD occurs in all types of dementia, and often are among the most prominent symptoms in the clinical course of the disease. Some disturbances like agitation and aggression may be disruptive and life-treating for patients and surrounding people. Non-pharmacological interventions should be recommended as a first line treatment unless BPSD symptoms are severe, persistent or recurrent. Drug treatment should have a specific target symptom. Atypical antipsychotics are widely used as the first line pharmacological approach to treat BPSD. Antidepressants, anxiolytics and antiepileptic's are also used. Treatment with cholinesterase inhibitors and/or memantine may delay the onset of BPSD and reduce the severity of some symptoms. Effective and safe treatment of BPSD should significantly improves the quality of life of patients and their caregivers. PMID- 25141582 TI - [The importance of imaging techniques in the modern treatment of multiple myeloma]. AB - The main symptom of multiple myeloma (MM) are pathological changes in bone. Imaging techniques are useful in determining the proper stage of the disease, follow-up after treatment and, as highlighted in recent times, in predicting prognosis and prediction. In the near future, radiographic examination of the whole body can be replaced by more sensitive techniques, such as low-dose computed tomography (CT) of the whole body. Magnetic resonance imaging (MRI) is a standard in the evaluation of bone marrow infiltration of the spine, allowing the prediction of the risk of vertebral fractures. Positron emission tomography (PET) coupled with CT (PET/CT) provides relevant information on the extent of lesions throughout the body, including soft tissues and is the best tool to distinguish active from inactive disease after treatment. Diagnostic imaging technique of PETIMR has the potential for precisely diagnosing in this condition. Prospective use of new imaging techniques in clinical practice in the near future will help to optimize the therapeutic management in individual cases of MM. PMID- 25141583 TI - [Intraneural ganglion of the peroneal nerve--two case reports]. AB - This paper describes two cases of gelatinous cyst of rare location within the peroneal nerve. Clinical picture was different in described patients. The gelatinous cyst was completely resected in both cases. The final diagnosis was established based on the histo-patological examination. PMID- 25141584 TI - [Cavernous haemangioma of the chest wall--case report]. AB - BACKGROUND: Cavernous hemangiomas are among the least common benign chest wall masses. The aim of this study is to present a case of a 40-year-old women, with a giant cavernous haemangioma arising in the left axillary area. CASE REPORT: A 40 year-old female, was referred to a pulmonologist, after her chest radiograph showed, in the upper field of the left lung, a peripherally located shading (13 cm long and 3.5 cm deep) connecting with the pleura. The skin above the change was not discoloured. Contrast-enhanced CT showed a cavernous haemangioma (17 cm long and 13 cm wide) located mostly in the left axillary area. The main vascular supply of the haemangioma came from a direct branch of the left axillary artery, the left intervertebral arteries (levels Ill-VII) and a branch of the left internal thoracic artery. CONCLUSIONS: This report illustrates a rare case of a giant cavernous haemangioma and the treatment challenges it poses. PMID- 25141585 TI - [Publishing activity of the Cracow Physicians Society]. PMID- 25141586 TI - [The Cracow Physicians Society and the medical faculty of Jagiellonian University -the past and the present]. AB - The Cracow Physicians Society (CPS) since inception in 1866, maintain close liaison with the Faculty of Medicine of the Jagiellonian University by the person of president, board members and ordinary members of the Society who are also employees of the University. They share a number of common initiatives. Many distinguished professors are honorary members of the Society. CPS annually rewards outstanding doctoral and postdoctoral works award named professor Sych, and also awards diplomas and medals to deserving individuals for professional, scientific and organizational work. CPS cooperates with the Association of Graduates of the Medical Faculties of the Jagiellonian University, Polish Academy of Learning and the Division of Krakow Polish Academy of Sciences and numerous specialized medical societies in the medical integration and to focus physicians around deontological and ethical problems, basic sciences, medical diagnostics, therapeutics, medical history and culture. PMID- 25141587 TI - [History of Jagiellonian University Clinic for Nervous and Mental Diseases in 100 anniversary]. AB - In the paper there have been presented the creation and activities of the Clinic of Neuropsychiatry in the period of 1914-1950 and the scientific and organizational work of professor J. Piltz (1870-1930). PMID- 25141588 TI - [Zbigniew Lewicki. Member of the founding committee of the Polish Urological Society. Biographical note]. PMID- 25141589 TI - Looking back, looking forward: 55 years of human factors. PMID- 25141590 TI - Using noninvasive brain stimulation to accelerate learning and enhance human performance. AB - OBJECTIVE: The authors evaluate the effectiveness of noninvasive brain stimulation, in particular, transcranial direct current stimulation (tDCS), for accelerating learning and enhancing human performance on complex tasks. BACKGROUND: Developing expertise in complex tasks typically requires extended training and practice. Neuroergonomics research has suggested new methods that can accelerate learning and boost human performance. TDCS is one such method. It involves the application of a weak DC current to the scalp and has the potential to modulate brain networks underlying the performance of a perceptual, cognitive, or motor task. METHOD: Examples of tDCS studies of declarative and procedural learning are discussed. This mini-review focuses on studies employing complex simulations representative of surveillance and security operations, intelligence analysis, and procedural learning in complex monitoring. RESULTS: The evidence supports the view that tDCS can accelerate learning and enhance performance in a range of complex cognitive tasks. Initial findings also suggest that such benefits can be retained over time, but additional research is needed on training schedules and transfer of training. CONCLUSION: Noninvasive brain stimulation can accelerate skill acquisition in complex tasks and may provide an alternative or addition to other training methods. PMID- 25141591 TI - Effects of cold environments on human reliability assessment in offshore oil and gas facilities. AB - OBJECTIVE: This paper proposes a new methodology that focuses on the effects of cold and harsh environments on the reliability of human performance. BACKGROUND: As maritime operations move into Arctic and Antarctic environments, decision makers must be able to recognize how cold weather affects human performance and subsequently adjusts management and operational tools and strategies. METHOD: In the present work, a revised version of the Human Error Assessment and Reduction Technique (HEART) methodology has been developed to assess the effects of cold on the likelihood of human error in offshore oil and gas facilities. This methodology has been applied to post-maintenance tasks of offshore oil and gas facility pumps to investigate how management, operational, and equipment issues must be considered in risk analysis and prediction of human error in cold environments. RESULTS: This paper provides a proof of concept indicating that the risk associated with operations in cold environments is greater than the risk associated with the same operations performed in temperate climates. It also develops guidelines regarding how this risk can be assessed. The results illustrate that in post-maintenance procedures of a pump, the risk value related to the effect of cold and harsh environments on operator cognitive performance is twice as high as the risk value when performed in normal conditions. CONCLUSION: The present work demonstrates significant differences between human error probabilities (HEPs) and associated risks in normal conditions as opposed to cold and harsh environments. This study also highlights that the cognitive performance of the human operator is the most important factor affected by the cold and harsh conditions. APPLICATION: The methodology developed in this paper can be used for reevaluating the HEPs for particular scenarios that occur in harsh environments since these HEPs may not be comparable to similar scenarios in normal conditions. PMID- 25141592 TI - Measures of reliance and compliance in aided visual scanning. AB - OBJECTIVE: We study the dependence or independence of reliance and compliance as two responses to alarms to understand the mechanisms behind these responses. BACKGROUND: Alarms, alerts, and other binary cues affect user behavior in complex ways. The suggestion has been made that there are two different responses to alerts--compliance (the tendency to perform an action cued by the alert) and reliance (the tendency to refrain from actions as long as no alert is issued). The study tests the degree to which these two responses are indeed independent. METHOD: An experiment tested the effects of the positive and negative predictive values of the alerts (PPV and NPV) on measures of compliance and reliance based on cutoff settings, response times, and subjective confidence. RESULTS: For cutoff settings and response times, compliance was unaffected by the irrelevant NPV, whereas reliance depended on the irrelevant PPV. For subjective estimates, there were no significant effects of the irrelevant variables. CONCLUSION: Results suggest that compliance is relatively stable and unaffected by irrelevant information (the NPV), whereas reliance is also affected by the PPV. The results support the notion that reliance and compliance are separate, but related, forms of trust. APPLICATION: False alarm rates, which affect PPV, determine both the response to alerts (compliance) and the tendency to limit precautions when no alert is issued (reliance). PMID- 25141593 TI - Predictive discomfort in single- and combined-axis whole-body vibration considering different seated postures. AB - OBJECTIVE: The aim of this study was to develop a predictive discomfort model in single-axis, 3-D, and 6-D combined-axis whole-body vibrations of seated occupants considering different postures. BACKGROUND: Non-neutral postures in seated whole body vibration play a significant role in the resulting level of perceived discomfort and potential long-term injury. The current international standards address contact points but not postures. METHOD: The proposed model computes discomfort on the basis of static deviation of human joints from their neutral positions and how fast humans rotate their joints under vibration. Four seated postures were investigated. For practical implications, the coefficients of the predictive discomfort model were changed into the Borg scale with psychophysical data from 12 volunteers in different vibration conditions (single-axis random fore-aft, lateral, and vertical and two magnitudes of 3-D). The model was tested under two magnitudes of 6-D vibration. RESULTS: Significant correlations (R = .93) were found between the predictive discomfort model and the reported discomfort with different postures and vibrations. The ISO 2631-1 correlated very well with discomfort (R2 = .89) but was not able to predict the effect of posture. CONCLUSION: Human discomfort in seated whole-body vibration with different non-neutral postures can be closely predicted by a combination of static posture and the angular velocities of the joint. APPLICATION: The predictive discomfort model can assist ergonomists and human factors researchers design safer environments for seated operators under vibration. The model can be integrated with advanced computer biomechanical models to investigate the complex interaction between posture and vibration. PMID- 25141594 TI - Serum and MRI biomarkers in mobile device texting: a pilot study. AB - OBJECTIVE: We aimed to determine if serum biochemical and MRI biomarkers differed between high volume (> or =230 texts sent/day; n = 5) and low volume (< or =25 texts sent/day; n = 5) texters. A secondary aim was to ascertain what correlations between the biochemical and imaging biomarkers could tell us about the pathophysiology of early onset tendinopathies. BACKGROUND: Text messaging has become widespread, particularly among college-aged young adults. There is concern that high rates of texting may result in musculoskeletal disorders, including tendinopathies. Pathophysiology of tendinopathies is largely unknown. METHOD: Ten females with a mean age of 20 were recruited. We examined serum for 20 biomarkers of inflammation, tissue degeneration, and repair. We used conventional MRI and MRI mean intratendinous signal intensity (MISI) to assess thumb tendons. Correlations between MISI and serum biomarkers were also examined. RESULTS: Three high volume texters had MRI tendinopathy findings as did one low volume texter. Increased serum TNF-RI was found in high volume texters compared to low volume texters, as were nonsignificant increases in MISI in two thumb tendons. Serum TNF RI and TNF-alpha correlated with MISI in these tendons, as did ILI-RI. CONCLUSION: These results suggest that early onset tendinopathy with concurrent inflammation may be occurring in prolific texters. Further studies with larger sample sizes are needed for confirmation. Application: High volume texting may be a risk factor for thumb tendinopathy in later years. Multidisciplinary research using biochemical and imaging biomarkers may be used to gain insight into pathophysiological processes in musculoskeletal disorders. PMID- 25141595 TI - Sizing firefighters: method and implications. AB - OBJECTIVE: This article reports new anthropometric information of U.S. firefighters for fire apparatus design applications (Study 1) and presents a data method to assist in firefighter anthropometric data usage for research-to practice propositions (Study 2). BACKGROUND: Up-to-date anthropometric information of the U.S. firefighter population is needed for updating ergonomic and safety specifications for fire apparatus. METHOD: A stratified sampling plan of three-age by three-race/ethnicity combinations was used to collect anthropometric data of 863 male and 88 female firefighters across the U.S. regions; 71 anthropometric dimensions were measured (Study I). Differences among original, weighted, and normality transformed data from Study 1 were compared to allowable observer errors (Study 2). RESULTS: On average, male firefighters were 9.8 kg heavier and female firefighters were 29 mm taller than their counterparts in the general U.S. population. They also have larger upper-body builds than those of the general U.S. population. The data in weighted, unweighted, and normality transformed modes were compatible among each other with a few exceptions. CONCLUSION: The data obtained in this study provide the first available U.S. national firefighter anthropometric information for fire apparatus designs. The data represent the demographic characteristics of the current firefighter population and, except for a few dimensions, can be directly employed into fire apparatus design applications without major weighting or nonnormality concerns. APPLICATION: The up-to-date firefighter anthropometric data and data method will benefit the design of future fire apparatus and protective equipment, such as seats, body restraints, cabs, gloves, and bunker gear. PMID- 25141596 TI - Measuring cognition in teams: a cross-domain review. AB - OBJECTIVE: The purpose of this article is twofold: to provide a critical cross domain evaluation of team cognition measurement options and to provide novice researchers with practical guidance when selecting a measurement method. BACKGROUND: A vast selection of measurement approaches exist for measuring team cognition constructs including team mental models, transactive memory systems, team situation awareness, strategic consensus, and cognitive processes. METHODS: Empirical studies and theoretical articles were reviewed to identify all of the existing approaches for measuring team cognition. These approaches were evaluated based on theoretical perspective assumed, constructs studied, resources required, level of obtrusiveness, internal consistency reliability, and predictive validity. RESULTS: The evaluations suggest that all existing methods are viable options from the point of view of reliability and validity, and that there are potential opportunities for cross-domain use. For example, methods traditionally used only to measure mental models may be useful for examining transactive memory and situation awareness. The selection of team cognition measures requires researchers to answer several key questions regarding the theoretical nature of team cognition and the practical feasibility of each method. CONCLUSIONS: We provide novice researchers with guidance regarding how to begin the search for a team cognition measure and suggest several new ideas regarding future measurement research. APPLICATIONS: We provide (1) a broad overview and evaluation of existing team cognition measurement methods, (2) suggestions for new uses of those methods across research domains, and (3) critical guidance for novice researchers looking to measure team cognition. PMID- 25141597 TI - Positive display polarity is particularly advantageous for small character sizes: implications for display design. AB - OBJECTIVE: To test the display luminance hypothesis of the positive polarity advantage and gain insights for display design, the joint effects of display polarity and character size were assessed with a proofreading task BACKGROUND: Studies have shown that dark characters on light background (positive polarity) lead to better legibility than do light characters on dark background (negative polarity), presumably due to the typically higher display luminance of positive polarity presentations. METHOD: Participants performed a proofreading task with black text on white background or white text on black background. Texts were presented in four character sizes (8, 10, 12, and 14 pt; corresponding to 0.22 degrees, 0.25 degrees, 0.31 degrees, and 0.34 degrees of vertical visual angle). RESULTS: A positive polarity advantage was observed in proofreading performance. Importantly, the positive polarity advantage linearly increased with decreasing character size. CONCLUSION: The findings are in line with the assumption that the typically higher luminance of positive polarity displays leads to an improved perception of detail. Application: The implications seem important for the design of text on such displays as those of computers, automotive control and entertainment systems, and smartphones that are increasingly used for the consumption of text-based media and communication. The sizes of these displays are limited, and it is tempting to use small font sizes to convey as much information as possible. Especially with small font sizes, negative polarity displays should be avoided. PMID- 25141598 TI - The role of number of tasks in determining the relevance of information. AB - OBJECTIVE: Our objective was to explore the value of considering the number of tasks that use a piece of information when calculating the relevance information has to an operator. BACKGROUND: Whereas frequency and criticality of information are often identified as information attributes, the number of tasks that use the information is rarely considered. METHOD: We calculated the relevance of pieces of information in air traffic control using criticality and frequency, and compared it to a formula that also considered the number of tasks. RESULTS: Including number of tasks resulted in information ranking that better accounted for aircraft relevant information, and better supported the information needs of air traffic controllers as determined by judgments of controllers. CONCLUSION: The attribute of number of tasks is valuable in calculating the relevance of information. Application: Interface designers should consider the number of tasks that use a particular piece of information when determining the placement of information within a display. PMID- 25141599 TI - Emergency medical equipment storage: benefits of visual cues tested in field and simulated settings. AB - OBJECTIVE: We tested the effectiveness of an illustrated divider ("the divider") for bedside emergency equipment drawers in an intensive care unit (ICU). In Study I, we assessed whether the divider increases completeness and standardizes the locations of emergency equipment within the drawer. In Study 2, we investigated whether the divider decreases nurses' restocking and retrieval times and decreases their workload. BACKGROUND: Easy access to fully stocked emergency equipment is important during emergencies. However, inefficient equipment storage and cognitively demanding work settings might mean that drawers are incompletely stocked and access to items is slow. METHOD: A pre-post-post study investigated drawer completeness and item locations before and after the introduction of the divider to 30 ICU drawers. A subsequent experiment measured item restocking time, item retrieval time, and subjective workload for nurses. RESULTS: At 2 weeks and 10 weeks after the divider was introduced, the completeness of the drawer increased significantly compared with before the divider was introduced. The divider decreased the variability of the locations of the 17 items in the drawer to 16% of its original value. Study 2 showed that restocking times but not retrieval times were significantly faster with the divider present For both tasks, nurses rated their workload lower with the divider. CONCLUSIONS: The divider improved the standardization and completeness of emergency equipment. In addition, restocking times and workload were decreased with the divider. APPLICATION: Redesigning storage for certain equipment using human factors design principles can help to speed and standardize restocking and ease access to equipment. PMID- 25141600 TI - Toward more usable electronic voting: testing the usability of a smartphone voting system. AB - OBJECTIVE: The goal of this research was to assess the usability of a voting system designed for smart-phones. BACKGROUND: Smartphones offer remote participation in elections through the use of pervasive technology. Voting on these devices could, among other benefits, increase voter participation while allowing voters to use familiar technology. However, the usability of these systems has not been assessed. METHOD: A mobile voting system optimized for use on a smartphone was designed and tested against traditional voting platforms for usability. RESULTS: There were no reliable differences between the smartphone based system and other voting methods in efficiency and perceived usability. More important, though, smartphone owners committed fewer errors on the mobile voting system than on the traditional voting systems. CONCLUSION: Even with the known limitations of small mobile platforms in both displays and controls, a carefully designed system can provide a usable voting method. Much of the concern about mobile voting is in the area of security; therefore, although these results are promising, security concerns and usability issues arising from mitigating them must be strongly considered. APPLICATION: The results of this experiment may help to inform current and future election and public policy officials about the benefits of allowing voters to vote with familiar hardware. PMID- 25141601 TI - Steering in a random forest: ensemble learning for detecting drowsiness-related lane departures. AB - OBJECTIVE: The aim of this study was to design and evaluate an algorithm for detecting drowsiness-related lane departures by applying a random forest classifier to steering wheel angle data. BACKGROUND: Although algorithms exist to detect and mitigate driver drowsiness, the high rate of false alarms and missed detection of drowsiness represent persistent challenges. Current algorithms use a variety of data sources, definitions of drowsiness, and machine learning approaches to detect drowsiness. METHOD: We develop a new approach for detecting drowsiness-related lane departures using steering wheel angle data that employ an ensemble definition of drowsiness and a random forest algorithm. Data collected from 72 participants driving the National Advanced Driving Simulator are used to train and evaluate the model. The model's performance was assessed relative to a commonly used algorithm, percentage eye closure (PERCLOS). RESULTS: The random forest steering algorithm had a higher classification accuracy and area under the receiver operating characteristic curve than PERCLOS and had comparable positive predictive value. The algorithm succeeds at identifying two key scenarios associated with the drowsiness detection task. These two scenarios consist of instances when drivers depart their lane because they fail to modulate their steering behavior according to the demands of the simulated road and instances when drivers correctly modulate their steering behavior according to the demands of the road. CONCLUSION: The random forest steering algorithm is a promising approach to detect driver drowsiness. The algorithm's ties to consequences of drowsy driving suggest that it can be easily paired with mitigation systems. PMID- 25141602 TI - Costs and benefits of more learner freedom: meta-analyses of exploratory and learner control training methods. AB - OBJECTIVE: Individual meta-analyses were conducted for six training methods as part of a U.S. Army basic research project. The objective was to identify evidence-based guidelines for the effectiveness of each training method, under different moderating conditions, for cognitive skill transfer in adult learning. Results and implications for two of these training methods, learner control (LC) and exploratory learning (EL), are discussed. LC provides learners with active control over training variables. EL requires learners to discover relationships and interactions between variables. BACKGROUND: There is mixed evidence on the effectiveness of both LC and EL learning methods on transfer relative to more guided training methods. Cognitive load theory (CLT) provides a basis for predicting that training strategies that manage intrinsic load of a task during training and minimize extraneous load will avail more resources that can be devoted to learning. METHOD: Meta-analyses were conducted using a Hedges's g analysis of effect sizes. Control conditions with little to no learner freedom were contrasted with treatment conditions manipulating more learner freedom. RESULTS: Overall more LC was no different from training with limited or no learner control, and more EL was less effective than limited or no exploration; however, each can be effective under certain conditions. Both strategies have been more effective for cognitive skill learning than for knowledge recall tasks. LC exhibited more benefit to very near transfer, whereas EL's benefit was to far transfer. CONCLUSION: Task type, transfer test, and transfer distance moderate the overall transfer cost of more learner freedom. APPLICATION: The findings are applicable to the development of instructional design guidelines for the use of LC and EL in adult skill training. PMID- 25141603 TI - Gametogenic development and spawning of the freshwater clam, Galatea paradoxa (Born 1778) from the Volta River Estuary, Ghana. AB - The study focused on the reproductive cycle of Galatea paradoxa (Born 1778), a major species for artisanal fishery in the Volta River estuary, Ghana. Condition indices and histological observation of the gonads revealed that G. paradoxa has a single spawning event between July and October. Gametogenesis started in December progressing steadily to a peak in June-July when spawning began until November when individuals were spent. Condition and gonadal indices showed a clear relationship with the gametogenic stages. PMID- 25141605 TI - Architecture for automation and telepresence in a marine hatchery laboratory. PMID- 25141604 TI - Effect of dietary bovine lactoferrin on rainbow trout (Oncorhynchus mykiss) fecundity and larval quality. PMID- 25141606 TI - Developmental staging and deformities characterization of the Eurasian perch, Perca fluviatilis. PMID- 25141607 TI - Providing harpacticoid copepods via floating sieve improves fish larval feeding success. PMID- 25141608 TI - Control of the selective pressure on microbes of the incoming water increases survival of marine fish larvae. PMID- 25141609 TI - Effect of red crab meal (Pleuroncodes planipes) on growth and digestive enzyme expression in the intestine of white shrimp (Litopenaeus vannamel). PMID- 25141610 TI - Bacterial community assembly in developing cod larvae (Gadus morhua). PMID- 25141611 TI - Inducer of heat shock protein 70: a new disease preventive option in aquaculture production systems. PMID- 25141612 TI - Could the eastern rock lobster, Sagmariasus verreauxi, be the best spiny lobster for aquaculture? PMID- 25141613 TI - Effects of combined phospholipids and selenium dietary contents on patterns of bone formation in the axial skeleton of Sparus aurata. PMID- 25141614 TI - Effect of phytochemicals on stress tolerance of Penaeus vannamei postlarvae. PMID- 25141615 TI - Experimental challenge: the quest for virulence -and protection. PMID- 25141616 TI - The key neuroendocrine regulators of the onset of puberty in the Atlantic bluefin tuna (Thunnus thynnus). PMID- 25141617 TI - Oxidative stress in sea bass Dicentrarchus labrax larvae: interaction of high dietary DHA contents and several antioxidant nutrients. PMID- 25141618 TI - High dietary levels of arachidonic acid not only affects the normal pigmentation patterns in post-metamorphic Senegalese sole larvae, but also disrupts the process of eye migration in pseudo-albino fish. PMID- 25141619 TI - Effect of broodstock diet on hepatic status and reproductive performance in Atlantic halibut (Hippoglossus hippoglossus L.) females. PMID- 25141620 TI - Fluorescent microspheres--a new approach to quantifying live feed intake in larval fish. PMID- 25141621 TI - Exploring the feeding mystery of leptocephalus larvae: a mouth full of teeth. PMID- 25141622 TI - Development of techniques and technology for embryonic and larval rearing of the European eel. PMID- 25141623 TI - Factors affecting sperm quality and emerging tools for sperm analysis. PMID- 25141624 TI - Epigenetic regulation of muscle development and growth in senegalese sole larvae. PMID- 25141625 TI - Does dietary amino acid profile modulate senegalese sole larvae protein metabolism? PMID- 25141626 TI - Gene expression profile of Litopenaeus vannamei juveniles fed different protein sources and detection of digestive-related genes by functional genomics. PMID- 25141627 TI - Influence of feeding regimes on the digestive enzyme profile and ultrastructure of digestive tract of Catla catla. PMID- 25141628 TI - Vibrio static activity in the culture of the Picochlorum sp. S1b can be attributed to the bacteria associated with the microalga. PMID- 25141629 TI - Towards the development of new quality indices in juvenile fish - relationship of caudal-fin morphology with the thermal history of juveniles. PMID- 25141630 TI - Investigating causes of skeletal malformation in yellowtail kingfish Seriola lalandi. PMID- 25141631 TI - Intensification of Litopenaeus vannamei larviculture. PMID- 25141632 TI - Effect of Sanolife MIC-F as larval fish probiotic on host stress resistance, histology, and microbiota in seabream. PMID- 25141633 TI - Genome-wide gene expression analysis during Solea sp. embryo-larval development. PMID- 25141634 TI - Studies of digestive physiology during early ontogeny of the Mayan cichlid Cichlasoma urophthalmus. PMID- 25141635 TI - Fish larval performance fed with copepods (Acartia grani) and the dinoflagellate (Oxyrrhis marina) as supplement: the case of dusky grouper (Epinephelus marginatus). PMID- 25141636 TI - Control of bacterial disease in cultures of marine larvae and live feed organisms by a probiotic bacterium. PMID- 25141637 TI - The function of wax esters in larval fish transition from endogenous to exogenous nutrition - are freshwater fish the exception or the rule? PMID- 25141638 TI - Digital image analysis to aid broodstock management and egg quality assessment. PMID- 25141639 TI - The application of ecological theory for microbial control in aquaculture. PMID- 25141640 TI - The development of new enrichment products and strategies for live feed in fish hatcheries. PMID- 25141641 TI - Effects of dietary Dunaliella salina extract and highly unsaturated fatty acids on the fecundity and lipid content of pond-reared Penaeus japonicus brood-stock. AB - Five basic diets containing fresh squid meat and trash fish were supplemented with different amount of Dunaleilla salina extract (DSE) and highly unsaturated fatty acids (HUFA). Supplemented diets were fed to pond-reared Penaeus japonicus broodstock. Diet A was solely squid and trash fish. Diets B 1 and B2 were supplemented with 400 and 600mg DSE.kg-1 diet, respectively. Diets C1 and C2 were supplemented with HUFA 5 and 10g.kg-1 and 400mg.kg-1DSE, respectively. The results showed that the group fed diet C2 had the best reproductive performance in all experimental groups. It had the highest proportion of spawns (73.5%) and egg production per female (589.0) than all the other experimental groups. The fatty acid composition strongly affected fecundity and stress tolerance of broodstock. The results showed that both HUFA and beta-carotene DSE may play role in stress tolerance and reproductive performance PMID- 25141642 TI - Linking weaning success to larval digestive capacity using radiolabelled peptide fractions. PMID- 25141643 TI - Fatty acid profile in eggs and newly hatched paralarvae of Octopus vulgaris collected from the wild, and after 1-5 days starvation. PMID- 25141644 TI - Vitamin A and K, two fat-soluble vitamins required for harmonic fish larval development. PMID- 25141645 TI - Influence of the forms and levels of dietary selenium on oxidative stress in rainbow trout fry. PMID- 25141646 TI - Lessons learned from gnotobiotic systems on the effect of bacteria on growth, survival, and gene expression in marine larvae. PMID- 25141647 TI - Correlation of saddleback syndrome with deformities of the pelvic fins and lateral line in European sea bass, Dicentrarchus labrax. PMID- 25141648 TI - Expression and activity of three digestive proteases in larvae of the totoaba (Totoaba macdonaldi). PMID- 25141649 TI - First feeding regimes for long-snout seahorse Hippocampus reidi larvae. AB - Seahorses are endangered species included in Appendix II of CITES from 2002 due to the progressive regression of wild populations. This study focused in Hippocampus reidi, one of the species with highest interest in trade, showing an increasing demand in the last decades. This study was conducted during 28 days to compare the effects of different time enrichment (0, 24, and 48h) for Artemia using a commercial product (Easy-Selco DHA INVE Aquaculture, Dendermonde, Belgium). Results showed no significant differences in growth between treatments until 21DAB, after which animals fed for 48h one enriched Artemia showed significantly better growth. Cumulative average survival during the first 14DAB was significantly higher in Oh treatment, while from 15DAB to the end of the experiment, no significantly differences were observed. PMID- 25141650 TI - Thermally-induced phenotypic plasticity in gilthead sea bream. PMID- 25141651 TI - Larval diet determines juvenile and adult phenotype in zebrafish (Danio rerio). PMID- 25141652 TI - Expression of skeletal myosin light chain 2 in gilthead sea bream (Sparus aurata, L): regulation and correlation to growth markers. PMID- 25141653 TI - Genomics in bivalve aquaculture. PMID- 25141654 TI - Early-feeding exposure to a plant-based diet improves its future acceptance and utilization in rainbow trout. PMID- 25141655 TI - Surface area estimation of the gut segments of Artemia franciscana nauplii fed with mnn9 yeast vs. wild type yeast. PMID- 25141656 TI - Domestication of Mahseer (Tor soro) in Indonesia. AB - Mahseer is an economically important fish in the world with a distribution from the Himalayan Mountains up to Southeast Asia. One species of Masheer is Tor soro in the Indonesian Archipelago. For a long time, T. soro has been collected from the wild and now is becoming rare. In addition, the degradation of its habitat is another problem. Hence, it is urgent that this species is saved from extinction. Domestication of T. soro from North Sumatra has been conducted since 1996. This paper reports the results of domestication of T. soro starting from collecting live specimens, genetic and morphometric characterizations, evaluation to breeding, and growing out. In 2010, domestication was successful to produce a second generation of young broodstocks and now the breeding technology is being shared with several provinces where T. soro exist. PMID- 25141657 TI - Content of essential fatty acids in cultivated Acartia tonsa nauplii fed a DHA deficient Tetraselmis sp. concentrate. PMID- 25141658 TI - Euryhaline rotifer Proales similis as initial live food for rearing fish larvae with small mouths. PMID- 25141659 TI - Ontogeny of the redox balance in relation to organogenesis in atlantic cod (Gadus morhua) larvae. PMID- 25141660 TI - Combating some of the crucial bottlenecks for calanoid copepod cultivation for live feed. PMID- 25141661 TI - Effects of probiotics on pompano (Trachinotus carolinus), common snook (Centropomus undecimalis), and red drum (Sciaenops ocellatus) larvae. PMID- 25141662 TI - Microparticulate enrichment of rotifer live diets with taurine and nutritional effects on northern rock sole (Lepidopsetta polyxystra) larvae. PMID- 25141663 TI - Is sinking mortality in southern bluefin tuna larvae caused by high light intensity? PMID- 25141664 TI - Effect of heat shock protein 70 (HSP70) homologue DnaK on gene expression of prophenoloxidase and transglutaminase in haemocytes of Litopenaeus vannamei. PMID- 25141665 TI - Maturation and spawning induction in Hawaiian opihi Cellana spp. by hormone GnRH. AB - Gonadotropin releasing hormone (GnRH) is a neuropeptide hormone whic plays an important role in control of the reproduction among vertebrates and some work is showing that it is active in invertebrate species. We matured and spawned the Hawaiian opihi Cellana spp. by using salmon GnRH analogue. In the first experiment on maturation, twelve adult opihi (3.18+/-0.23cm, shell length) were injected weekly with salmon GnRHa at dose of 250ng.g-1 body weight (BW) for a 6 week period. Gonad development was assessed using gonadosomatic index (GSI) and histological techniques. GSI incorporated with histological analysis showed that the gonads reached full maturation after 4 weeks. GSI increased significantly (31%) in comparison to the control group of saline solution injection did not produce any maturity in opihi. For the spawning trial, eight ripe opihi were administered a single injection at dose of 1000ng.g-1 BW. The results showed that an average of 33% of the animal spawned in 4-6h after hormone injection. Fertilized eggs developed through embryo and to the com plete larval stage of veligers. Our preliminary findings in this study provide a new aspect of hormone controlling reproduction of opihi, which could be applied in opihi aquaculture. PMID- 25141666 TI - Promoting of bacteria growth by manipulating carbon/nitrogen ratio and use as microalgae substitution for filter feeders: a demonstration on Artemia culture. PMID- 25141667 TI - Nanoparticles as a novel delivery system for vitamin C administration in aquaculture. PMID- 25141668 TI - Bacteriophage application as a management strategy in shrimp hatcheries. PMID- 25141669 TI - Reproductive capacity of Hemiculter leucisculus (Basilewsky, 1855) in Uzbekistan. PMID- 25141670 TI - Development of maturation diet for penaeid shrimp using herbal extracts. PMID- 25141671 TI - Associated effects of bacteria on Octopus tetricus larvae rearing. PMID- 25141672 TI - The effect of ph on the fertilizability of rainbow trout (Oncorhynchus mykiss) eggs stored in a chilled state. AB - To verify the observation that fertilizability of stored rainbow trout eggs is affected by deviations in pH (Komrakova and Holtz, 2011) freshly collected eggs were immersed in coelomic fluid adjusted to pH 6, 7, 8, 9, or 10 (3 replicates each) and stored at 2 degreesC. At 0, 1, 24, 48, and 96h, pH was measured and eggs were inseminated with cryopreserved semen. Egg development until the eyed stage proceeded normally in all cases. However hatching rates, amounting to 70% in controls (pH 8, SEM 0.02), were reduced to 50% in samples exposed to pH 7 or pH 9 and to 40% and 30% in samples exposed to pH 6 and pH 10, respectively. In conclusion, when eggs are subjected to coelomic fluid with deviating pH, the damage afflicted upon the eggs will not become evident until they are due to hatch. PMID- 25141673 TI - The effect of different phytoplankton species and commercial enrichment products on the fatty acid profile, enzyme activity, and overall condition of the rotifer Brachionus Plicatilis. PMID- 25141674 TI - Culture systems in the coastal complexes which are used in the process of red king crab artificial reproduction in Russia. PMID- 25141675 TI - Dynamic of efficiency of MS-222 as an anaesthetic for tench Tinca tinca (L.) larvae. PMID- 25141676 TI - Emergence of cannibalism in European percid fish-size heterogeneity or natural born killers consequence? PMID- 25141677 TI - Allometric growth in the Nannacara anomala regan, 1905 (Cichlidae, pisces). PMID- 25141678 TI - Microencapsulated diets for altricial freshwater fish larvae: production and evaluation. PMID- 25141680 TI - Host-induced increase of sea bass mortality in a gnotobiotic challenge test with Vibrio anguillarum. PMID- 25141679 TI - Gene regulation of Atlantic cod (Gadus morhua) larvae with focus on lipid digestion and phospholipid metabolism. PMID- 25141681 TI - Ontogeny of the digestive system of Octopus bimaculatus paralarvae. PMID- 25141682 TI - Low-cost production of the marine thraustochytrid isolate, Schizochytrium sp. LEY7 as larval live feed enrichement for the mangrove snapper, Lutjanus sp. PMID- 25141683 TI - Importance of DHA for first feeding pikeperch larvae--influence on behavioural responses. PMID- 25141684 TI - Use of Phaeobacter sp. probiotic bacteria for the rearing of sea bass larvae (Dicentrarchus labrax). PMID- 25141685 TI - Digestive and immune responses to probiotics or prebiotics in percid larvae. PMID- 25141686 TI - Do immunostimulants affect sperm quality in Senegalese sole? PMID- 25141687 TI - Evaluation of daily rhythms in feeding activity and digestive functions in gilthead sea bream (Sparus (Sparus aurata) larvae. PMID- 25141688 TI - Advances in larval rearing protocols of sole, Solea senegalensis. PMID- 25141689 TI - Effect of increasing DHA content in new weaning diets for longfin yellowtail (Seriola rivoliana). PMID- 25141690 TI - Evaluation of colour development of rosy barb, Puntius conchonius (Hamilton) during ontogeny. PMID- 25141691 TI - DHA requirement of larval Japanese flounder Paralichthys olivaceus in the rotifer feeding period. PMID- 25141692 TI - Investigating the essential fatty acid requirements of the cephalopod Sepia officinalis: a molecular approach. PMID- 25141693 TI - Effect of Senegalese sole broodstock nutrition on early larval performance and metabolism of long-chain polyunsaturated fatty acids (DHA and EPA). PMID- 25141694 TI - Gene expression is strongly regulated by nutrients in first feeding Atlantic cod larvae (Gadus morhua). PMID- 25141695 TI - Identification and migration of primordial germ cells in Atlantic salmon (Salmo Salar) and Atlantic Cod (Gadus morhua). PMID- 25141696 TI - Interaction between dietary levels of LC-PUFA and vegetable oil sources in Senegalese sole (Solea senegalensis) post-larvae: puzzling results suggesting complete biosynthesis pathway from C18 PUFA to DHA. PMID- 25141697 TI - Effects of glucose and probiotic supplementation in nursing juvenile clam, Meretrix lyrata. AB - This study was conducted to evaluate the effects of different glucose concentration on the survival and growth rate of juvenile hard clam, Meretrix lyrata. Juvenile clams M lyrata were cultured with algae from a tilapia greenwater system and different concentrations of glucose (0, 35, and 70microg.l 1). After 70 days of culture, highest survival rate was obtained with 35microg.l 1 glucose supplementation (99.5-100%). However, in highest concentration of glucose, weight gain and shell length of clams reached highest values (p<0.05). Our findings showed that supplementation of probiotics and suitable glucose concentration in the nursery period could increase survival and growth rate of clams. PMID- 25141698 TI - Effect of environmental factors on heritability and its biometrics of Artemia franciscana Vinh Chau by mass selection of small sized cysts. PMID- 25141699 TI - Potential uses of gut weed Enteromorpha spp. as a feed for herbivorous fish. AB - Three separate experiments were performed to assess the potential use of gut weeds Enteromorpha spp. as a food source for herbivorous fish. The fresh or dried gut weeds were used as a direct feed to replace commercial feed in an alternative approach for feeding spotted seat (Scatophagus argus), red tilapia (Oreochromis sp.), and giant gourami (Osphronemus goramy) juveniles for 60 days, 45 days, and 56 days, respectively. Four feeding regimes were applied to triplicate tanks and fish was fed daily either commercial feed or gut weed: (1) single commercial feed everyday as a control treatment, (2) single gut weed daily and 2 alternative feeding regimes where (3) 1 day commercial feed and 1 consecutive day gut weed or and (4) 2 consecutive days gut weed. The results indicated that survival of experimental fish was not affected by the feeding treatments. Growth performance of the S. argus fed single gut weed was not significantly different from the control group (P>0.05). Growth rates of Oreochromis sp. and O. goramy in the alternative feeding treatments were comparable to the control treatment. Application of the combined feeding regimes, feed conversion ratio could be reduced from 26.1 to 57.8%. These results indicated that fresh and dried gut weed can be used as a feed to substitute commercial feed for herbivorous fish. Moreover, using gut weeds as a feed could improve water quality in the rearing tanks. PMID- 25141700 TI - Influence of virulent and avirulent bacterial strains on HSP70 content of Artemia instar II larvae. PMID- 25141701 TI - New approaches for Artemia pond culture. AB - A project for intensive culture of Artemia in Vinhchau solar saltwork was funded by Soctrang Authority. The aim of this project is to increase the average cyst yield of 50kg.ha-1.crop, and to build up a stable culture technique with a better yield for local farmers. Multiple laboratory experiments were set up with inert food including fermented rice bran, tiger shrimp feed (PL15), as well as their combination with live algae (Chaetoceros). Results showed that, under laboratory conditions, fermented rice bran and tiger shrimp feed can be used as supplemental food sources. The shrimp feed alone or in combination with algae always gave better cyst production compared to the others, but should not account for more than 50% of the diet. In the field trials, aeration of Artemia ponds also increased cyst yields (from 195.8+/-44.2 to 207+/-46.1kg.ha-1.crop with 6 and 12 aeration a day, respectively) compared to ponds with no aeration (88.2+/ 27.5kg.ha-1.crop), however the returns on investment (ROI=2.73-2.71 with aera tion vs. 2.24 without) are not significantly different. Utilization of fermented rice bran (20kg.ha-1.day) and shrimp feed (6kg.ha-1.day) as a supplementary feed during pond production in combination with greenwater supplies (10% of pond volume daily) resulted in higher yields (96.0+/-15.9 and 157.2+/-15.0kg.ha 1.crop, respectively) than traditional culture; Shrimp feed as a supplemental feed supported the cyst yield but their negative effect was at a high cost vs. traditional culture and use of fermented rice bran. Based on the cyst yield and ROI, fermented rice bran should be a promising item for poor farmers. PMID- 25141702 TI - Use of poly-beta-hydroxybutyrate in bivalve larviculture. PMID- 25141703 TI - Improving visual environment in cod larval rearing by factorial designs. PMID- 25141704 TI - The protective and intestinal microbiota steering effect of a novel heat shock inducer on brine shrimp larvae. PMID- 25141705 TI - Ontogeny of kiss2 and kiss1r gene expression in gilthead sea bream (Sparus aurata) larvae. PMID- 25141706 TI - Tank wall color affects swimbladder inflation in Eurasian perch, Perca fluviatilis l., under controlled conditions. PMID- 25141707 TI - Burbot, Lota lota, L., larvae requirements for Artemia sp. nauplii during experimental rearing in laboratory conditions. PMID- 25141708 TI - The impact of quorum sensing-disrupting compounds on survival and growth of giant freshwater prawn (Macrobrachium rosenbergii) larvae. PMID- 25141709 TI - Effect of DHA on the expression of the delta6-desaturase during larval development of yellow snapper, Lutjanus argentiventris. PMID- 25141710 TI - Selection and identification of probiotic bacteria for use in the marine shrimp culture. PMID- 25141711 TI - Amino acid profile and consumption during the embryonic development and yolk-sac larvae of Pacific red snapper Lutjanus peru. PMID- 25141712 TI - Selection study of potential probiotic bacteria for shrimp hatcheries in New Caledonia. PMID- 25141713 TI - Identification of nitrifying bacteria in intensive shrimp ponds in Soc Trang province, Vietnam by biochemical test and molecular technique. PMID- 25141714 TI - Can dietary phospholipid and trace mineral supplementation influence zebrafish reproductive performance? PMID- 25141715 TI - The development of an axenic blue mussel (Mytilus edulis) larvae test system. PMID- 25141716 TI - Review on the ontogeny of larvae from neotropical freshwater fishes: the pacu model. PMID- 25141717 TI - Larval rearing protocols for meagre Argyrosomus regius. PMID- 25141718 TI - Effects on the skeleton development in reared gilthead sea bream (Sparus aurata). PMID- 25141719 TI - Bacterial community compositions of ejected intestine of juvenile sea cucumber and the effect of sea sediment Bacillus on in vivo antagonism against pathogenic Vibrio splendidus. PMID- 25141720 TI - Pavlova - a "new" microalgae candidate species for live feed cultivation and fish larvae nutrition. PMID- 25141721 TI - Endogenous metabolism of unsaturated fatty acids in Artemia nauplii as determined through incubation with 14C-labelled fatty acid substrates. PMID- 25141722 TI - Assessment of protein digestive capacity and utilisation during ontogeny of Senegalese sole larvae: a tracer study using in vivo produced radiolabelled peptide fractions. PMID- 25141723 TI - Recent advances in Seriola dumerilli culture. PMID- 25141724 TI - Genetic variability of wild horseshoe crabs (Tachypleus gigas) from west coast of Peninsular Malaysia. PMID- 25141725 TI - Virulence genes and quorum sensing of Vibrio harveyi. PMID- 25141726 TI - Lipid digestion in first feeding larvae - visualization in vivo. PMID- 25141727 TI - The self-fertilizing mangrove killifish Kryptolebias marmoratus as a model fish for aquacultural study. PMID- 25141728 TI - Optimum phospholipids and antioxidant levels to develop novel microdiets for gilthead sea bream larvae. PMID- 25141729 TI - European sea bass larval early weaning development using greenwater and synbiotic in Alexandria, Egypt. PMID- 25141730 TI - An assessment of biosecurity and hazard management practices in the larviculture of shrimp (Penaeus monodon), Bangladesh. PMID- 25141731 TI - The effects of dietary poly-beta-hydroxybutyrate on growth, feed utilization, and survival of Nile tilapia (Oreochromis niloticus) fry. PMID- 25141732 TI - Quantitative characteristics of Atlantic halibut (Hippoglossus hippoglossus L) egg production throughout the reproductive season and their relationship to embryo and larval quality. PMID- 25141733 TI - Microbial characterization of enriched Artemia sp. at two different temperatures and enrichments. PMID- 25141734 TI - Evaluation of probiotic bacteria against aeromonads syndrome in common carp (Cyprinus carpio L.) in simple axenic larviculture. AB - Evaluation of probiotics, Bacillus firmus and B. coagulans against Aeromonas hydrophila in axenic common carp larviculture was conducted. The highest egg hatching rate was obtained from the axenic system + probiotic bacteria (AP) (98.33%), followed by axenic system (A) (96.67%); axenic system + probiotic + A. hydrophila (AC) (93.33%); non-axenic system (NA) (93.33%); and axenic system + A. hydrophila (AH) (83.33%). 100% survival rate (SR) was obtained from all treatments, except AH (90%). The highest weight (0.013g) was obtained from the A treatment, followed by AC (0.0127g), AP (0.0123g), AH (0.012g), and NA (0.005g). In conclusion, the axenic system can be used to improve common carp larviculture, and further use of B. coagulans and B. firmus was able to control Aeromonads syndrome during the larviculture stage. PMID- 25141735 TI - Effect of poly-hydroxybutyrate on growth and enzymatic activity of Chinese mitten crab, Eriocheir sinensis, juvenile. PMID- 25141736 TI - Egg production, egg hatching success, and population growth of the calanoid copepod Acartia grani (Calanoida, acartiidae) fed with eight different diets. PMID- 25141737 TI - Current status of crab larviculture in Thailand and development of a diet for domesticated broodstock. PMID- 25141738 TI - Ontogenetic development of the digestive system in reared fat snook (Centropomus parallelus) larvae. PMID- 25141739 TI - Cholecystokinin and tryptic enzyme activity in sea bass (Dicentrarchus labrax) larvae: a regulatory loop and the impact of feeding regimes. PMID- 25141740 TI - Reproduction of European eel and larval culture--state of the art. PMID- 25141741 TI - Applying of freshwater rotifer (Brachionus angularis) in rearing newly hatching fries of marble goby (Oxyeleotris marmoratus). PMID- 25141742 TI - Copepods enhance growth and development in Atlantic cod (Gadus morhua L.) larvae. PMID- 25141743 TI - A gnotobiotic model system: the case of Artemia franciscana. PMID- 25141744 TI - Muscle growth of triploid Atlantic cod larvae (Gadus morhua). PMID- 25141745 TI - Studies on the characterisation of biomarkers of nutritionally-derived stress in paralarval cultures of the common octopus (Octopus vulgaris). PMID- 25141746 TI - Effects of feeding time, rates, and frequencies on survival rate of stripped catfish fry (Pangasianodon hypophthalmus) fed by freshwater rotifers (Brachionus angularis). PMID- 25141747 TI - Thyroid regulation in teleost embryonic and larval development - can it be a promise for aquaculture? AB - The role of thyroid hormones (THs) in fish development is often overlooked and particularly neglected for the embryonic and larval stages of fish. We used a set of experiments to elucidate the importance of TH in embryonic to early larval development in zebrafish. In the first set of experiments we used morpholino antisense oligonucleotides to knock down TH downstream genes and showed that the depletion of TH in early development resulted in severe deformities, developmental delay, and pigmentation, which could be quantitatively recovered by subsequent TH treatments. In the second set of experiments, blocking TH deposition into zebrafish eggs by treating parental fish with goitrogens resulted not only initial low TH content in eggs, but also subsequent loss of egg laying ability. Overall, these data strongly suggest a key role of TH in early development in fish, providing its worth to be investigated for effective use in reproduction and larviculture. PMID- 25141748 TI - Water management and biocontrol - selection of probiotic strains. PMID- 25141749 TI - Low Artemia consumption strategies in larval shrimp rearing. PMID- 25141750 TI - Orthogonal analysis of elements affecting the formation of cystocarps on female gametophyte of Gracilariopsis lemaneiformis. PMID- 25141751 TI - Microparticles delivery system in gnotobiotic European sea bass larvae (Dicentrarchus labrax, L. 1758). PMID- 25141752 TI - Development of an NNV-free larvae rearing system and production of SPR grouper fingerlings. PMID- 25141753 TI - The impact of quorum sensing on motility in Vibrio harveyi. PMID- 25141754 TI - Multiple vitellogenin yolk precursors in European sea bass (Dicentrarchus labrax). PMID- 25141755 TI - Effect of light conditions on the population growth of rotifers. PMID- 25141756 TI - Ontogeny of the digestive tract of the omnivorous fish Chelon labrosus. PMID- 25141757 TI - Application of a multi-strain probiotic improves utilization of microalgae in Litopenaeus vannamei post-larvae. PMID- 25141758 TI - Diverse thermoresponsive behaviors of uncharged UCST block copolymer micelles in physiological medium. AB - Three amphiphilic diblock copolymers, representative of three types of block copolymer (BCP) design, were synthesized using reversible addition-fragmentation chain-transfer (RAFT) polymerization. All of them have a same uncharged block of a random copolymer of commercially available acrylamide and acrylonitrile, P(AAm co-AN), and exhibit a composition-tunable upper critical solution temperature (UCST). We show that by coupling a common P(AAm-co-AN) block with either hydrophobic polystyrene (PS) or hydrophilic poly(dimethylacrylamide) (PDMA) or the lower critical solution temperature (LCST) polymer of poly(N,N dimethylaminoethyl methacrylate) (PDMAEMA), the BCP micelles formed in water or in phosphate buffered saline (PBS) can display diverse and UCST-dictated changes in response to temperature variations, such as the reversible dispersion aggregation of micelles, dissolution-formation of micelles, and reversal of micelle core and corona. The results point out that P(AAm-co-AN) is a robust UCST polymer that can be introduced into controlled polymer architectures producible by RAFT, the same way as using the extensively studied LCST counterparts like poly(N-isopropylacrylamide) (PNIPAM). This ability should make the door wide open to exploring new thermosensitive polymers based on the thermosensitivity opposite to the LCST. PMID- 25141759 TI - Addition of intrarectal local analgesia to periprostatic nerve block improves pain control for transrectal ultrasonography-guided prostate biopsy: a systematic review and meta-analysis. AB - OBJECTIVES: To evaluate the efficacy and safety of combined intrarectal local analgesia and periprostatic nerve block versus periprostatic nerve block alone for pain control during transrectal ultrasound-guided prostate biopsy. METHODS: We comprehensively searched PubMed, Embase and the Cochrane Library trials. Studies comparing the two techniques were identified and pooled for cumulative analysis. The outcome measurements included visual pain scales of three consecutive procedures of transrectal ultrasound-guided prostate biopsy, as well as short-term postoperative complication rates. RESULTS: There were 18 studies that were finally eligible for the quantitative analysis involving 2076 participants. Combined modalities significantly reduced the pain associated with probe manipulation (weighted mean difference -2.06, 95% confidence interval -2.77 to -1.35, P < 0.001), anesthesia infiltration (weighted mean difference -1.45, 95% confidence interval -2.20 to -0.70, P < 0.001) and needle biopsy (weighted mean difference -0.55, 95% confidence interval -0.76 to -0.34, P < 0.001). Subgroup analyses assessing different local analgesics showed that local anesthetics are generally more effective than myorelaxant and non-steroidal anti inflammatory drugs. Lidocaine-prilocaine cream proved the most effective in pain control regardless of the origin of pain. No significant difference of short-term postoperative complications (fever, dysuria, acute urinary retention, hematuria, hematospermia and rectal bleeding) was found between the two techniques. The only side-effect associated with local analgesics was headache reported in studies using glyceryl trinitrate ointment. CONCLUSIONS: Combined modalities show better analgesic efficacy than periprostatic nerve block alone for transrectal ultrasound-guided prostate biopsy without increased morbidities. Among the various local analgesics, lidocaine-prilocaine cream seems to offer the best overall efficacy. PMID- 25141760 TI - Health related quality of life in patients with chronic gastritis and peptic ulcer and factors with impact: a longitudinal study. AB - BACKGROUND: The assessment of Health Related Quality of Life (HRQOL) has been applied as a significant outcome indicator for patients with chronic diseases. No HRQOL study, however, has looked at HRQOL in patients with chronic gastritis and peptic ulcers. This paper focuses on comparing HRQOL in patients with chronic gastritis and peptic ulcers and examining the factors that influence the HRQOL of such patients. Results can be used for making decisions in clinical trials as well as aiding individual management and preventive care of these diseases. METHODS: The Chinese version of the SF-36 (CSF-36) was administered twice to 244 patients with chronic gastritis and peptic ulcers. Mean scores across the two disease groups were compared using t-tests, change over time was analyzed with paired samples t-tests, and factors predicting HRQOL were investigated using the univariate general linear model. RESULTS: The mean domain scores of patients with chronic gastritis were lower than those for patients with peptic ulcers, with the exception of physical functioning. Both groups had lower HRQOL compared with population norms. Mean domain scores increased after treatment in both groups. HRQOL in patients with these two chronic diseases differed by age, education level, marriage, income, and gender, but their explanatory power was relatively low. CONCLUSION: Quality of life of patients with chronic gastritis was lower than that of patients with peptic ulcers, which was lower than population norms. Quality of life in both patients groups was associated with socio-demographic risk factors. PMID- 25141761 TI - Persistently high estimates of late night, indoor exposure to malaria vectors despite high coverage of insecticide treated nets. AB - BACKGROUND: It has been speculated that widespread and sustained use of insecticide treated bed nets (ITNs) for over 10 years in Asembo, western Kenya, may have selected for changes in the location (indoor versus outdoor) and time (from late night to earlier in the evening) of biting of the predominant species of human malaria vectors (Anopheles funestus, Anopheles gambiae sensu stricto, and Anopheles arabiensis). METHODS: Mosquitoes were collected by human landing catches over a six week period in June and July, 2011, indoors and outdoors from 17 h to 07 h, in 75 villages in Asembo, western Kenya. Collections were separated by hour of the night, and mosquitoes were identified to species and tested for sporozoite infection with Plasmodium falciparum. A subset was dissected to determine parity. Human behavior (time going to bed and rising, time spent indoors and outdoors) was quantified by cross-sectional survey. Data from past studies of a similar design and in nearby settings, but conducted before the ITN scale up commenced in the early 2000s, were compared with those from the present study. RESULTS: Of 1,960 Anopheles mosquitoes collected in 2011, 1,267 (64.6%) were morphologically identified as An. funestus, 663 (33.8%) as An. gambiae sensu lato (An. gambiae s.s. and An. arabiensis combined), and 30 (1.5%) as other anophelines. Of the 663 An. gambiae s.l. collected, 385 were successfully tested by PCR among which 235 (61.0%) were identified as An. gambiae s.s. while 150 (39.0%) were identified as An. arabiensis. Compared with data collected before the scale-up of ITNs, daily entomological inoculation rates (EIRs) were consistently lower for An. gambiae s.l. (indoor EIR = 0.432 in 1985-1988, 0.458 in 1989-1990, 0.023 in 2011), and An. arabiensis specifically (indoor EIR = 0.532 in 1989-1990, 0.039 in 2009, 0.006 in 2011) but not An. funestus (indoor EIR = 0.029 in 1985-1988, 0.147 in 1989-1990, 0.010 in 2009 and 0.103 in 2011). Sporozoite rates were lowest in 2009 but rose again in 2011. Compared with data collected before the scale-up of ITNs, An. arabiensis and An. funestus were more likely to bite outdoors and/or early in the evening (p < 0.001 for all comparisons). However, when estimates of human exposure that would occur indoors (pii) or while asleep (pis) in the absence of an ITN were generated based on human behavioral patterns, the changes were modest with >90% of exposure of non ITN users to mosquito bites occurring while people were indoors in all years. The proportion of bites occurring among non-ITN users while they were asleep was >=90% for all species except for An. arabiensis. For this species, 97% of bites occurred while people were asleep in 1989-1990 while in 2009 and 2011, 80% and 84% of bites occurred while people were asleep for those not using ITNs. Assuming ITNs prevent a theoretical maximum of 93.7% of bites, it was estimated that 64 77% of bites would have occurred among persons using nets while they were asleep in 1989-1990, while 20-52% of bites would have occurred among persons using nets while they were asleep in 2009 and 2011. CONCLUSIONS: This study found no evidence to support the contention that populations of Anopheles vectors of malaria in Asembo, western Kenya, are exhibiting departures from the well-known pattern of late night, indoor biting characteristic of these typically highly anthropophilic species. While outdoor, early evening transmission likely does occur in western Kenya, the majority of transmission still occurs indoors, late at night. Therefore, malaria control interventions such as ITNs that aim to reduce indoor biting by mosquitoes should continue to be prioritized. PMID- 25141762 TI - Mortality from acute appendicitis is associated with complex disease and co morbidity. AB - BACKGROUND: Studies evaluating mortality in patients with acute appendicitis focus on the outcomes of appendicectomy alone. We hypothesize this may not be representative of what happens in clinical practice as a small proportion of patients with acute appendicitis undergo procedures other than appendicectomy, for example, caecectomy or right hemicolectomy. To clarify the issue, the authors evaluated Australian adult patients who died with a primary diagnosis of acute appendicitis regardless of whether they underwent an operation or the type of operation performed. METHODS: A cross-sectional analysis of systematically collected mortality data from the Australian and New Zealand Audit of Surgical Mortality was conducted on adults who died in hospital with a primary diagnosis of acute appendicitis between January 2009 and December 2012. RESULTS: Twenty-six patients died with a primary diagnosis of acute appendicitis. The median age was 83 years and the median number of co-morbidities was three. Four patients died without surgery due to their family's wishes. Twenty-two patients were treated surgically: five for right hemicolectomy, four for laparoscopic/McBurney appendicectomy, 10 for laparotomy with appendicectomy, two for unknown method of appendicectomy and one for open abscess drainage. CONCLUSION: Most adult patients who died following surgery for acute appendicitis did not undergo simple appendicectomy but underwent more complicated procedures for complex appendicitis. PMID- 25141763 TI - New functions for old genes: Pax6 and Mitf in eye pigment biogenesis. PMID- 25141765 TI - Recent advances in characterization of nonviral vectors for delivery of nucleic acids: impact on their biological performance. AB - INTRODUCTION: Nucleic acid delivery is a complex process that requires transport across numerous extracellular and intracellular barriers, whose impact is often neglected during optimization studies. As such, the development of nonviral vectors for efficient delivery would benefit from an understanding of how these barriers relate to the physicochemical properties of lipoplexes and polyplexes. AREAS COVERED: This review focuses on the evaluation of parameters associated with barriers to delivery such as blood and immune cells compatibility which, as a collective, may serve as a useful prescreening tool for the advancement of nonviral vectors in vivo. An outline of the most relevant rationally developed polyplexes and lipoplexes for clinical application is also given. EXPERT OPINION: The evaluation of scientifically recognized parameters enabled the identification of systemic delivered nonviral vectors' behavior while in blood as one of the key determinants of vectors function and activity both in vitro and in vivo. This multiparametric approach complements the use of in vitro efficacy results alone for prescreening and improves in vitro-in vivo translation by minimizing false negatives. Further, it can aid in the identification of meaningful structure function-activity relationships, improve the in vitro screening process of nonviral vectors before in vivo use and facilitate the future development of potent and safe nonviral vectors. PMID- 25141766 TI - Urban African American women's explanations of recurrent chlamydia infections. AB - OBJECTIVE: To explore reasons for the high chlamydia recurrence rate among African American (AA) urban women. DESIGN: In this phenomenological qualitative study, young AA urban women with recurrent chlamydia were interviewed using open ended questions guided by the conceptual framework of the health belief model (HBM). SETTING: The study was set in three urban health clinics in Michigan. PARTICIPANTS: Ten African American adolescents, age 15 to 19, participated. METHODS: In face-to-face recorded interviews, participants shared their personal experiences and viewpoints on what led to their recurrent chlamydia infections. The data were transcribed and analyzed through hand coding and NVivo 8 a qualitative software package. RESULTS: Overall, participants demonstrated significant knowledge deficits about the seriousness of chlamydia compared to other sexually transmitted infections (STIs). After reinfection, their perceived susceptibility changed: condom use was seen as beneficial and perceived barriers to condom use diminished as participants gained a new sense of empowerment. CONCLUSION: Chlamydia infection among African American urban adolescents is nearly 3 times that of the general population. Lack of education is still a barrier to STI prevention. Participants reported a desire to receive counseling and support from the health care staff. A STI care model that includes education, counseling, and regular screening of high-risk adolescents should be considered. Further research, using the HBM or similar theoretical models, are needed to gauge the success of any planned or implemented intervention. PMID- 25141767 TI - Crowdsourcing yields a new standard for kinks in protein helices. AB - Kinks are functionally important structural features found in the alpha-helices of proteins. Structurally, they are points at which a helix abruptly changes direction. Current kink definition and identification methods often disagree with one another. Here we describe a crowdsourcing approach to obtain a reliable gold standard set of kinks. Using an online interface, we collected more than 10,000 classifications of 300 helices into straight, curved, or kinked categories. We found that participants were better at discriminating between straight and not straight helices than between kinked and curved helices. Surprisingly, more obvious kinks were not necessarily identified as more localized within the helix. We present a set of 252 helices where more than 50% of the participants agree on a classification. This set can be used as a reliable gold standard to develop, train, and compare computational methods. An interactive visualization of the results is available online at http://opig.stats.ox.ac.uk/webapps/ahah/php/experiment_results.php . PMID- 25141764 TI - Changing faces in virology: the dutch shift from oncogenic to oncolytic viruses. AB - Viruses have two opposing faces. On the one hand, they can cause harm and disease. A virus may manifest directly as a contagious disease with a clinical pathology of varying significance. A viral infection can also have delayed consequences, and in rare cases may cause cellular transformation and cancer. On the other hand, viruses may provide hope: hope for an efficacious treatment of serious disease. Examples of the latter are the use of viruses as a vaccine, as transfer vector for therapeutic genes in a gene therapy setting, or, more directly, as therapeutic anticancer agent in an oncolytic-virus therapy setting. Already there is evidence for antitumor activity of oncolytic viruses. The antitumor efficacy seems linked to their capacity to induce a tumor-directed immune response. Here, we will provide an overview on the development of oncolytic viruses and their clinical evaluation from the Dutch perspective. PMID- 25141768 TI - XacR - a novel transcriptional regulator of D-xylose and L-arabinose catabolism in the haloarchaeon Haloferax volcanii. AB - The haloarchaeon Haloferax volcanii degrades D-xylose and L-arabinose via oxidative pathways to alpha-ketoglutarate. The genes involved in these pathways are clustered and were transcriptionally upregulated by both D-xylose and L arabinose suggesting a common regulator. Adjacent to the gene cluster, a putative IclR-like transcriptional regulator, HVO_B0040, was identified. It is shown that HVO_B0040, designated xacR, encodes an activator of both D-xylose and L-arabinose catabolism: in DeltaxacR cells, transcripts of genes involved in pentose catabolism could not be detected; transcript formation could be recovered by complementation, indicating XacR dependent transcriptional activation. Upstream activation promoter regions and nucleotide sequences that were essential for XacR mediated activation of pentose-specific genes were identified by in vivo deletion and scanning mutagenesis. Besides its activator function XacR acted as repressor of its own synthesis: xacR deletion resulted in an increase of xacR promoter activity. A palindromic sequence was identified at the operator site of xacR promoter, and mutation of this sequence also resulted in an increase and thus derepression of xacR promoter activity. It is concluded that the palindromic sequence represents the binding site of XacR as repressor. This is the first report of a transcriptional regulator of pentose catabolism in the domain of archaea. PMID- 25141769 TI - Comparison of total energy expenditure assessed by two devices in controlled and free-living conditions. AB - The objective of this study was to evaluate the validity of total energy expenditure (TEE) provided by Actiheart and Armband. Normal-weight adult volunteers wore both devices either for 17 hours in a calorimetric chamber (CC, n = 49) or for 10 days in free-living conditions (FLC) outside the laboratory (n = 41). The two devices and indirect calorimetry or doubly labelled water, respectively, were used to estimate TEE in the CC group and FLC group. In the CC, the relative value of TEE error was not significant (p > 0.05) for Actiheart but significantly different from zero for Armband, showing TEE underestimation ( 4.9%, p < 0.0001). However, the mean absolute values of errors were significantly different between Actiheart and Armband: 8.6% and 6.7%, respectively (p = 0.05). Armband was more accurate for estimating TEE during sleeping, rest, recovery periods and sitting-standing. Actiheart provided better estimation during step and walking. In FLC, no significant error in relative value was detected. Nevertheless, Armband produced smaller errors in absolute value than Actiheart (8.6% vs. 12.8%). The distributions of differences were more scattered around the means, suggesting a higher inter-individual variability in TEE estimated by Actiheart than by Armband. Our results show that both monitors are appropriate for estimating TEE. Armband is more effective than Actiheart at the individual level for daily light-intensity activities. PMID- 25141770 TI - Regression-based estimation of ERP waveforms: I. The rERP framework. AB - ERP averaging is an extraordinarily successful method, but can only be applied to a limited range of experimental designs. We introduce the regression-based rERP framework, which extends ERP averaging to handle arbitrary combinations of categorical and continuous covariates, partial confounding, nonlinear effects, and overlapping responses to distinct events, all within a single unified system. rERPs enable a richer variety of paradigms (including high-N naturalistic designs) while preserving the advantages of traditional ERPs. This article provides an accessible introduction to what rERPs are, why they are useful, how they are computed, and when we should expect them to be effective, particularly in cases of partial confounding. A companion article discusses how nonlinear effects and overlap correction can be handled within this framework, as well as practical considerations around baselining, filtering, statistical testing, and artifact rejection. Free software implementing these techniques is available. PMID- 25141771 TI - Lower heart rate variability predicts increased level of C-reactive protein 4 years later in healthy, nonsmoking adults. AB - BACKGROUND: Inflammation and vagally mediated heart rate variability (vmHRV) have been implicated in a number of conditions including diabetes and cardiovascular disease. Consistent with the inflammatory reflex termed the 'cholinergic anti inflammatory pathway', numerous cross-sectional studies have demonstrated negative associations between vmHRV and inflammatory markers such as C-reactive protein (CRP). The only prospective study, however, showed the opposite: higher CRP at baseline predicted higher high-frequency heart rate variability (HF-HRV) at follow-up. Thus, additional studies are needed to examine the prospective association between vmHRV and CRP. METHODS: Healthy employees participated in a voluntary on-site health assessment. Blood samples and ambulatory heart rate recordings were obtained, and night-time HF-HRV was calculated. Useable heart rate data were available in 2007 for 106 nonsmoking employees (9% women; age 44.4 +/- 8 years), all of whom returned for an identical follow-up health assessment in 2011. Bootstrapped (500 replications) bivariate (r) and partial Pearson's correlations (ppc) adjusting for sex, age and body mass index at baseline (2007) were calculated. RESULTS: Zero-order correlations indicated that higher HF-HRV was associated with lower levels of CRP at both time-points (2007: r = -0.19, P < 0.05; 2011: r = -0.34, P < 0.001). After adjustment, HF-HRV remained a significant predictor of CRP (ppc = -0.20, P < 0.05). CONCLUSION: In this study, we have provided in vivo support for the cholinergic anti-inflammatory pathway in humans. Cardiac vagal modulation at baseline predicts level of CRP 4 years later. Our findings have important implications for the role of vmHRV as a risk factor for cardiovascular disease morbidity and mortality. Interventions targeted at vmHRV might be useful in the prevention of diseases associated with elevated systemic inflammation. PMID- 25141772 TI - Prevalence and validity of self-reported smoking in Indigenous and non-Indigenous young adults in the Australian Northern Territory. AB - BACKGROUND: In this study, we used data from Australia's Northern Territory to assess differences in self-reported smoking prevalence between the Indigenous and non-Indigenous populations. We also used urinary cotinine data to assess the validity of using self-reported smoking data in these populations. METHODS: The Aboriginal Birth Cohort (ABC) is a prospective study of 686 Aboriginal babies born in Darwin 1987-90. The Top End Cohort (TEC) is a study of non-Indigenous adolescents, all born in Darwin 1987-91. In both studies, participants aged between 16 and 21 years, were asked whether they smoked. Urinary cotinine measurements were made from samples taken at the same visits. RESULTS: Self reported smoking prevalence was 68% in the ABC and 14% in the TEC. Among the self reported non-smokers, the median cotinine levels were higher in the ABC (33 ng/ml) than in the TEC (5 ng/ml), with greater percentages of reported non smokers in the under 50 ng/ml group in the TEC than in the ABC CONCLUSIONS: Prevalence of smoking was much higher in the ABC than in the TEC. The higher cotinine levels in ABC non-smokers may reflect an underestimated prevalence, but is also likely to reflect higher levels of passive smoking. A broader approach encompassing social, cultural and language factors with increased attention to smoking socialisation factors is required. PMID- 25141773 TI - A patient with a painless neck tumour revealed as a carotid paraganglioma: a case report. AB - Carotid paragangliomas are usually slowly enlarging and painless lateral neck masses. These mostly benign lesions are recognized due to their typical location, vessel displacement and specific blood supply, features that are usually seen on different imaging modalities. Surgery for carotid paraganglioma can be associated with immediate cerebrovascular complications or delayed neurological impairment.We are reporting the case of a 36-year-old man who presented with a painless mass on the right side of his neck 11 months after being treated for testicular cancer. After a fine-needle aspiration biopsy, he was diagnosed with a testicular cancer lymph node metastasis. Neck US and fluorine [F-18]-fluorodeoxy D-glucose (FDG) PET-CT showed no signs of hypervascularity or vessel displacement. The patient underwent a level II to V functional neck dissection. During the procedure, suspicion of a carotid paraganglioma was raised and the tumour was carefully dissected from the walls of the carotid arteries with minimal blood loss and no cranial nerve dysfunction.The histology report revealed carotid paraganglioma with no metastasis in the rest of the lymph nodes. The patient's history of testicular germ cell tumour led to a functional neck dissection during which a previously unrecognized carotid paraganglioma was removed.Surgery for carotid PG can be associated with complications that have major impact on quality of life. A thorough assessment of the patient and neck mass must therefore be performed preoperatively in order to perform the surgical procedure under optimal conditions. PMID- 25141774 TI - Acute systemic sarcoidosis complicating ustekinumab therapy for chronic plaque psoriasis. PMID- 25141775 TI - Is the solar system's galactic motion imprinted in the Phanerozoic climate? AB - A new delta(18)O Phanerozoic database, based on 24,000 low-Mg calcitic fossil shells, yields a prominent 32 Ma oscillation with a secondary 175 Ma frequency modulation. The periodicities and phases of these oscillations are consistent with parameters postulated for the vertical motion of the solar system across the galactic plane, modulated by the radial epicyclic motion. We propose therefore that the galactic motion left an imprint on the terrestrial climate record. Based on its vertical motion, the effective average galactic density encountered by the solar system is 0.172+/-0.006stat+/-0.006sysM?pc-3. This suggests the presence of a disk dark matter component. PMID- 25141776 TI - Systematic evaluation of percutaneous radiofrequency ablation versus percutaneous ethanol injection for the treatment of small hepatocellular carcinoma: a meta analysis. AB - BACKGROUND: Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) have been used for patients with hepatocellular carcinoma (HCC). However, which therapy is superior remains to be further elucidated. We aimed to conduct a systematic review to assess survival and local tumor recurrence rate with RFA compared with PEI therapy for HCC. METHODS: We conducted systematic review and meta-analysis of randomized controlled trials (RCTs) published up to 2014 in PubMed, MEDLINE, EMBASE, EBSCO, Springer, Ovid and the Cochrane library. Only RCTs that evaluated survival rate and occurrence of HCC between RFA and PEI therapy were included. The OR (odds ratio) with a 95% confidence interval (CI) was calculated by the Revman 5.0 software. RESULTS: A total of six studies including 983 HCC patients were eligible for this analysis. The survival rate showed a significant benefit under RFA therapy over PEI at 1-year (P = 0.02, OR = 1.88, 95% CI: 1.09 to 3.22), 2-years (P = 0.0003, OR = 2.06, 95% CI: 1.39 to 3.05) and 3-years (P = 0.0007, OR = 1.68, 95% CI: 1.25 to 2.27). Likewise, RFA achieved significantly lower rates of local tumor recurrence over PEI at 1-year (P = 0.002, OR = 0.43, 95% CI: 0.26 to 0.73), 2-year (P = 0.03, OR = 0.33, 95% CI: 0.12 to 0.88) and 3-year (P = 0.003, OR = 0.61, 95% CI: 0.43 to 0.84). CONCLUSIONS: The current evidence suggests that RFA is superior to PEI in better survival and local disease control for small HCCs <5 cm in diameter and that RFA is worthy of promotion in clinical applications. PMID- 25141777 TI - A new approach to asymmetric synthesis of infectocaryone. AB - A useful and flexible strategy for synthesis of (-)- and (+)-infectocaryone from commercial sugars is developed. The key step of the synthesis is a new-type Diels Alder reaction with good chemoselectivity and stereoselectivity, in which a mixture of alkene regioisomers in a dynamic equilibrium is employed as chiral dienophiles for the first time. PMID- 25141778 TI - Microbes are not bound by sociobiology: response to Kummerli and Ross-Gillespie (2013). AB - In recent years, sociobiology has been extended to microorganisms. Viewed through this lens, the microbial world is replete with cooperative behaviors. However, little attention has been paid to alternate hypotheses, making many studies self confirming. Somewhat apart is a recent analysis of pyoverdin production-a paradigmatic public good and social trait-by Pseudomonas, which has revealed discord between predictions arising from sociobiology and the biology of microbes. This led the authors, Zhang and Rainey (Z&R), to question the generality of the conclusion that pyoverdin is a social trait, and to question the fit between the sociobiology framework and microbiology. This has unsettled Kummerli and Ross-Gillespie (K&R), who in a recent "Technical Comment" assert that arguments presented by Z&R are flawed, their experiments technically mistaken, and their understanding of social evolution theory naive. We demonstrate these claims to be without substance and show the conclusions of K&R to be based on a lack of understanding of redox chemistry and on misinterpretation of data. We also point to evidence of cherry-picking and raise the possibility of confirmation bias. Finally, we emphasize that the sociobiology framework applied to microbes is a hypothesis that requires rigorous and careful appraisal. PMID- 25141780 TI - The relationship between moderate-to-vigorous intensity physical activity and insulin resistance, insulin-like growth factor (IGF-1)-system 1, leptin and weight change in healthy women during pregnancy and after delivery. AB - CONTEXT: Childbearing is considered to be a significant risk factor for developing overweight and obesity. Physical activity might influence weight change via hormonal changes. OBJECTIVE: To test the hypothesis that higher levels of moderate-to-vigorous intensity physical activity (MVPA) are positively associated with maternal insulin sensitivity and reduce IGF-1, IGFBP-3, leptin levels, bodyweight gain/retention and birth weight. METHODS: In healthy nulliparous women, weight measurements were carried out and blood was collected during pregnancy in the 15th, 25th and 35th week, and after delivery at 6, 26 and 52 weeks. At 15 and 35 weeks of pregnancy and 26 weeks postpartum, MVPA was measured using accelerometers. In linear regression models, the relationship between MVPA below or above the median with metabolic and weight outcomes was assessed, adjusted for maternal BMI, age and smoking. RESULTS: Moderate-to vigorous intensity physical activity (MVPA) decreased significantly during pregnancy, but was very low already in early pregnancy. Insulin resistance and leptin levels increased during pregnancy and decreased significantly after delivery (all P < 0.05). After adjustment, insulin, IGFBP-3 and BMI were significantly lower at 15 weeks of pregnancy in women with MVPA above the median compared to those with MVPA below the median. After 15 weeks of pregnancy, no significant associations were observed between hormonal levels and MVPA. MVPA was neither related to weight retention, nor to birth weight. CONCLUSION: Except in early pregnancy, MPVA was not related to metabolic outcomes. In addition, MVPA during pregnancy was not related to weight retention or birth weight. PMID- 25141779 TI - Evaluation of a new person-centered integrated care model in psychiatry. AB - The present study evaluated a new integrated treatment concept offering inpatient care, acute psychiatric day hospital and outpatient treatment by the same therapeutic team. 178 patients participated in this randomized controlled trial. Data on psychopathology, global and social functioning, patient satisfaction, continuity of care and administrative data was gathered on admission, throughout the course of treatment, upon discharge and at 1-year follow-up. In addition, the physicians in charge rated the therapeutic relationship. The data analysis consists of group-wise comparisons and regression analyses (cross-tabulations and chi(2) test statistics for categorical data and Mann-Whitney U tests for continuous data). Differences between groups over time were analyzed with a series of generalized linear mixed model. The integrated care group showed a significant reduction in psychopathological impairment (20.7%) and an improvement of psychosocial functioning (36.8%). The mean number of days before re-admission was higher in the control group when compared to the integrated care group (156.8 vs. 91.5). There was no difference in the number of re-admissions and days spent in psychiatric institutions. This new approach offers a treatment model, which facilitates continuity of care. Beside it improves psychopathological outcome measures and psychosocial functioning in patients with mental illness. PMID- 25141781 TI - Retraction: Topography of Retinal Ganglion Cells in the Dromedary Camel (Camelus dromedarius). AB - This article released online on July 30, 2014 as advance publication has been retracted by the Editorial Board of Journal of Veterinary Medical Science due to a violation of the journal's "Information for Authors". PMID- 25141782 TI - Early development and osteoporosis and bone health. AB - Osteoporosis is a skeletal disorder characterized by low bone mass and micro architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) and hypothalamo-pituitary adrenal (HPA) axes, and recent work has suggested a central role for vitamin D. Epidemiological studies have shown that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Childhood growth rates have been directly linked to the risk of hip fracture many decades later, and now evidence is emerging from experimental animal studies that support these observational data. Recent studies have also highlighted epigenetic phenomena as potential mechanisms underlying the findings from epidemiological studies. PMID- 25141783 TI - The developmental origins of sarcopenia: from epidemiological evidence to underlying mechanisms. AB - Sarcopenia is defined as the loss of skeletal muscle mass and strength with age. There is increasing recognition of the serious health consequences in terms of disability, morbidity and mortality as well as major healthcare costs. Adult determinants of sarcopenia including age, gender, size, levels of physical activity and heritability have been well described. Nevertheless, there remains considerable unexplained variation in muscle mass and strength between older adults that may reflect not only the current rate of loss but the peak attained earlier in life. To date most epidemiological studies of sarcopenia have focused on factors modifying decline in later life; however, a life course approach to understanding sarcopenia, additionally, focuses on factors operating earlier in life including developmental influences. The epidemiological evidence linking low birth weight with lower muscle mass and strength is strong and consistent with replication in a number of different groups including children, young and older adults. However, most of the evidence for the cellular, hormonal, metabolic and molecular mechanisms underlying these associations comes from animal models. The next stage is to translate the understanding of mechanisms from animal muscle to human muscle enabling progress to be made not only in earlier identification of individuals at risk of sarcopenia but also in the development of beneficial interventions across the life course. PMID- 25141784 TI - Searching for very early precursors of autism spectrum disorders: the Hamamatsu Birth Cohort for Mothers and Children (HBC). AB - Autism spectrum disorders (ASD) are life-long neurodevelopmental conditions. The pathophysiology is poorly understood, and the clinical diagnosis can only be made through behavioural assessments. The prevalence of ASD has increased eight-fold over the last three decades. Paralleling this rise, research interest in the disorder has been accumulating, centering on two aspects: risk factors that would explain the increase in prevalence, and precursors that could predict an emergence of ASD prior to 2 years of age. As regard factors responsible for the increased prevalence, an increasing trend of low birthweight (4.2% in 1980 v. 9.6% in 2006 at Japan) and advanced paternal age at birth are potentially implicated. To explore these issues, and to yield an early diagnostic algorithm for ASD, the authors initiated the ongoing Hamamatsu Birth Cohort for Mothers and Children (HBC) in 2007. The strengths of the HBC include frequent, direct face-to face assessments of all the participating mothers and children during the first 4 years of life (12 assessments); this depth of assessments will disclose subtle changes in the developmental domains of individuals with ASD, which might otherwise be overlooked. A total of 1200 pregnant women are to be recruited by the end of 2010. Assembled information comprises a range of variables related to the mother's characteristics and child development. The comprehensiveness of the HBC will provide an informative data source that will elucidate early trajectories of children with ASD in addition to revealing detailed, developmental properties of typically developing children. PMID- 25141785 TI - Birth cohort patterns suggest that infant survival predicts adult mortality rates. AB - Dramatic improvements in life expectancy during the 20th century are commonly attributed to improvements in either health care services or the social and economic environment. We evaluated the hypothesis that improving infant survival produces improvements in adult (?40 years) mortality rates. We used generalizations of age-period-cohort models of mortality that explicitly account for the exponential increase of adult mortality rates with age (Gompertz model) to determine whether year of birth or year of death better correlate with observed patterns of adult mortality. We used data from Canada and nine other countries obtained from the Human Mortality Database. Five-year birth cohorts between 1900 and 1944 showed consistent improvements in age-specific mortality rates. According to the akaike information criteria, Gompertz-Cohort models significantly better predicted the observed patterns of adult mortality than Gompertz-Period models, demonstrating that year of birth correlates better with adult mortality than year of death. Infant mortality strongly correlated with the initial set point of adult mortality in a Gompertz-period-cohort. Selected countries exhibited elevated adult mortality rates for the 1920 and 1944 birth cohorts, suggesting that the period before the first year of life may be uniquely vulnerable to environmental influences. These findings suggest that public health investments in the health of mothers and children can be a broad primary prevention strategy to prevent the chronic diseases of the adult years. PMID- 25141786 TI - Altered hepatic insulin signalling in male offspring of obese mice. AB - Individuals exposed in utero to maternal obesity have increased risk of developing type 2 diabetes mellitus and obesity in adulthood. The molecular mechanisms underlying this association are unknown. We have therefore used a murine model of maternal obesity, in which the offspring of obese dams develop hyperinsulinaemia by 3 months of age indicative of insulin resistance. Here, we investigate the effects of maternal diet-induced obesity on the expression/phosphorylation of key hepatic insulin signalling proteins and the expression of anti-oxidant enzymes in male offspring. At 3 months of age, offspring of obese dams had decreased levels of insulin receptor substrate (IRS) 1 (P < 0.01), whereas the ratio of phosphorylated IRS1 Ser307 to total IRS1 was significantly increased (P < 0.001), suggesting that it was less active. Protein expression of the PI3K p85alpha subunit was decreased (P < 0.01) and there was a tendency for phosphorylation of Akt at Ser473 to be reduced (P = 0.08) in the offspring of obese dams. protein kinase Czeta (P < 0.001) and glycogen synthase kinase 3beta (P < 0.05) levels were increased in these animals in comparison with controls. Maternal obesity also resulted in increased phosphorylation of p38 mitogen-activated protein kinase at Thr180/Tyr182 (P < 0.01) and raised c-Jun N terminal kinase 1 expression (P < 0.5) in the offspring. The expression of antioxidant enzymes was also affected by maternal obesity with CuZnSOD (P < 0.001) and glutathione reductase (P < 0.05) being increased, whereas glutathione peroxidase 1 was reduced (P < 0.05) in the offspring. We conclude that maternal obesity leads to alterations in hepatic insulin signalling protein expression and phosphorylation. These molecular changes may contribute to the development of insulin resistance. PMID- 25141787 TI - Abdominal wall fat index in neonates: correlation with birth size. AB - Low birth weight is associated with obesity in later life and a more central fat distribution has a positive correlation with cardiovascular disease. However, the correlation between visceral adiposity in newborns and birth size is unknown. We measured the visceral adiposity in 118 newborns using the abdominal wall fat index (AFI), ratio between the maximum thickness of preperitoneal and the minimum thickness of subcutaneous fat evaluated by ultrasound. There was a weak negative correlation between AFI and birth weight (r = -0.197; P = 0.033) but not with birth length (r = -0.118; P = 0.201), body mass index (r = -0.138; P = 0.176) and abdominal circumference (r = 0.063; P = 0.497). In conclusion, we suggest that AFI is a useful parameter for evaluating the fat distribution in newborns and that visceral adiposity has a weak negative correlation with birth weight. PMID- 25141789 TI - Bandgap opening/closing of graphene antidot lattices with zigzag-edged hexagonal holes. AB - How to predict the bandgap size of graphene antidot lattices (GALs) is a key problem in the field of graphene-based nanoelectronics. Here, we have obtained the universal rules on bandgap opening/closing of GALs with zigzag-edged hexagonal holes (ZH-GALs), as well as the means to control the bandgap size. In the simple case that the electronic property depends on the choice of the supercell, the quantitative relationship between Eg and the density/diameter of antidots is fitted. Turning to complex structures, we reveal that the bandgap opening in ZH-GALs results mainly from the intervalley scattering. In this interpretation, according to their relative position, the antidots can be divided into three categories. A relatively large bandgap appears in ZH-GALs, only when the numbers of the three categories are unequal. This could be explained based on a mechanism similar to diffraction. A formula according to the explanation is provided to estimate the bandgap, which can be used to predict the electronic properties of GALs and guide the design of semiconductor and photoelectronic devices based on GALs. PMID- 25141788 TI - Identification of novel epitopes from human papillomavirus type 18 E7 that can sensitize PBMCs of multiple HLA class I against human cervical cancer. AB - BACKGROUND: To identify the novel epitopes from the human papillomavirus type 18 E7 which can sensitize PBMCs of four different major HLA class I A allele. METHODS: Twenty-four synthetic overlapping 15-amino acid peptides were screened by measuring the frequency of CD8+ cytotoxic T lymphocytes (CTLs)-producing interferon-gamma (IFN-gamma) by using flow cytometry and ELISpot assays and selected peptides were validated for cytolytic activity by using the 51Cr release assay. Truncated peptides in the selected epitopes were tested to determine the important residues using ELISpot and 51Cr release assay. RESULTS: Among 24 peptides, E781-95DDLRAFQQLFLNTLS (#21) and E789-103LFLNTLSFVCPWCAS (#23) induced significantly higher Th 1 response including IFN-gamma production and in vitro cytotoxicity of PBMCs of four different HLA-A alleles against cervical cancer cells than that of other peptides and the negative control (no peptide sensitization). In E781-95 (#21), amino acid position 81, 82 (N-terminus) and 92, 94, 95 (C-terminus) for HLA-A*02:02 and 24:02, and 81, 82 (N-terminus) and 92, 95 (C-terminus) for HLA-A*11:01 and 33:03 were important to elicit Th1 response of PBMCS. In E789-103 (#23), residue 100 and103 (C-terminus) were important to elicit the CD8+ CTL response in HLA-A*02:01, 11:01 and 33:03 and 100, 101, and 103 (C-terminus) were important to elicit the CD8+ CTL response in HLA-A*24:02. CONCLUSIONS: E781-95 (#21) and E789-103 (#23) were identified as novel epitopes from HPV18 E7 which could sensitized PBMCs of four different HLA class I (HLA A*02:01, 24:02, 11:01 and 33:03). These epitopes could be useful for immune monitoring and immunotherapy for HPV 18+ cervical cancer. PMID- 25141790 TI - Temporal and spatial mapping of red grouper Epinephelus morio sound production. AB - The goals of this project were to determine the daily, seasonal and spatial patterns of red grouper Epinephelus morio sound production on the West Florida Shelf (WFS) using passive acoustics. An 11 month time series of acoustic data from fixed recorders deployed at a known E. morio aggregation site showed that E. morio produce sounds throughout the day and during all months of the year. Increased calling (number of files containing E. morio sound) was correlated to sunrise and sunset, and peaked in late summer (July and August) and early winter (November and December). Due to the ubiquitous production of sound, large-scale spatial mapping across the WFS of E. morio sound production was feasible using recordings from shorter duration-fixed location recorders and autonomous underwater vehicles (AUVs). Epinephelus morio were primarily recorded in waters 15-93 m deep, with increased sound production detected in hard bottom areas and within the Steamboat Lumps Marine Protected Area (Steamboat Lumps). AUV tracks through Steamboat Lumps, an offshore marine reserve where E. morio hole excavations have been previously mapped, showed that hydrophone-integrated AUVs could accurately map the location of soniferous fish over spatial scales of <1 km. The results show that passive acoustics is an effective, non-invasive tool to map the distribution of this species over large spatial scales. PMID- 25141791 TI - Simulation: a new approach to teaching ethics. AB - The importance of ethical conduct in health care was acknowledged as early as the fifth century in the Hippocratic Oath and continues to be an essential element of clinical practice. Providers face ethical dilemmas that are complex and unfold over time, testing both practitioners' knowledge and communication skills. Students learning to be health care providers need to develop the knowledge and skills necessary to negotiate complex situations involving ethical conflict. Simulation has been shown to be an effective learning environment for students to learn and practice complex and overlapping skills sets. However, there is little guidance in the literature on constructing effective simulation environments to assist students in applying ethical concepts. This article describes realistic simulations with trained, standardized patients that present ethical problems to graduate-level nurse-midwifery students. Student interactions with the standardized patients were monitored by faculty and peers, and group debriefing was used to help explore students' emotions and reactions. Student feedback postsimulation was exceedingly positive. This simulation could be easily adapted for use by health care education programs to assist students in developing competency with ethics. PMID- 25141794 TI - Structure and hypolipidaemic activity of fucoidan extracted from brown seaweed Sargassum henslowianum. AB - The aim of this study is to elucidate the structure and investigate the hypolipidaemic activity of a fucoidan extracted from brown seaweed Sargassum henslowianum collected at Hai Van-Son Cha peninsula, Hue province, Vietnam by using tandem electrospray ionisation mass spectrometry. The results demonstrated that the fucoidan has alpha(1 -> 3)-linked L-fucopyranose backbone and sulphate groups occupied mostly at C-2, C-4 and sometimes at C-3 position of fucose residues. The results of in vivo bioactivity examination revealed that the fucoidan in the dose of 100 mg/kgP/day by oral administration helped decrease cholesterol, triglyceride and LDL-cholesterol levels on obese mice. PMID- 25141792 TI - Sexual problems during the first 2 years of adjuvant treatment with aromatase inhibitors. AB - INTRODUCTION: Sexual dysfunction has only recently been recognized as a highly prevalent side effect of adjuvant aromatase inhibitor (AI) therapy for breast cancer. AIMS: A cross-sectional survey using standardized measures of female sexual function was designed to provide a detailed view of sexual problems during the first 2 years of adjuvant AI therapy and secondarily to examine whether sexual dysfunction leads to nonadherence to this therapy. METHODS: Questionnaires were mailed to all 296 women in a breast oncology registry who had been prescribed a first-time AI for localized breast cancer 18-24 months previously. MAIN OUTCOME MEASURES: Items assessed medication adherence, demographic, and medical information. Scales included the Female Sexual Function Index, the Menopausal Sexual Interest Questionnaire, the Female Sexual Distress Scale Revised, the Breast Cancer Prevention Trial Eight Symptom Scale to assess menopausal symptoms, and the Merck Adherence Estimator((r)) . RESULTS: Questionnaires were returned by 129 of 296 eligible women (43.6%). Respondents were 81% non-Hispanic white with a mean age of 63 and 48% had at least a college degree. Only 15.5% were nonadherent. Ninety-three percent of women scored as dysfunctional on the Female Sexual Function Index, and 75% of dysfunctional women were distressed about sexual problems. Although only 52% of women were sexually active when starting their AI, 79% of this group developed a new sexual problem. Fifty-two percent took action to resolve it, including 24% who stopped partner sex, 13% who changed hormone therapies, and 6% who began a vaginal estrogen. Scores on the Adherence Estimator (beliefs about efficacy, value, and cost of medication) were significantly associated with adherence (P = 0.0301) but sexual function was not. CONCLUSIONS: The great majority of women taking AIs have sexual dysfunction that is distressing and difficult to resolve. Most continue their AI therapy, but a large minority cease sexual activity. PMID- 25141793 TI - MCMV avoidance of recognition and control by NK cells. AB - Natural killer (NK) cells play an important role in virus control during infection. Many viruses have developed mechanisms for subversion of NK cell responses. Murine cytomegalovirus (MCMV) is exceptionally successful in avoiding NK cell control. Here, we summarize the major MCMV evasion mechanisms targeting NK cell functions and their role in viral pathogenesis. The mechanisms by which NK cells regulate CD8(+) T cell response, particularly with respect to the role of NK cell receptors recognizing viral antigens, are discussed. In addition, we discuss the role of NK cell receptors in generation and maintenance of memory NK cells. Final part of this review illustrates how the NK cell response and its viral regulation can be exploited in designing recombinant viral vectors able to induce robust and protective CD8(+) T cell response. PMID- 25141795 TI - Improved outcomes associated with a revised quality measure for continuing perioperative beta-blockade. AB - IMPORTANCE: The Surgical Care Improvement Project perioperative beta-blocker (BB) (SCIP-BB) continuation measure was revised in 2012 to incorporate inpatient BB continuation after discharge from the postanesthesia care unit. OBJECTIVE: To determine whether adherence to the original or revised SCIP-BB measure is associated with decreased adverse events. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using national Veterans Affairs patient-level data on adherence to the original SCIP-BB measure and inpatient BB continuation for operations between July 2006 and August 2009. METHODS: Data for SCIP-BB measure adherence, inpatient BB continuation, and patient and procedure risk variables were used to estimate the associations between adherence to the original and revised SCIP-BB measures and outcomes of major adverse cardiovascular or cerebrovascular events (MACCEs) and their components of cardiovascular events, cerebrovascular events, and 30-day mortality. In addition to unadjusted estimates, propensity score matching and bootstrapping were used to estimate the associations and generate 95% CIs. MAIN OUTCOMES AND MEASURES: Major adverse cardiovascular or cerebrovascular events. RESULTS: Of 14,420 nonemergent operations with at least 2 postoperative inpatient days, 13,170 (91.3%) adhered to the original SCIP-BB measure, and 480 (3.3%) experienced a MACCE. Propensity score-matched analyses showed that adherence to the original SCIP-BB measure was not associated with MACCEs (odds ratio [OR], 1.00; 95% CI, 0.66-1.54) but was associated with increased cerebrovascular events (OR, 3.01; 95% CI, 1.00-10.07). Adherence to the revised SCIP-BB measure occurred in 11,597 (80.4%), and in matched analysis adherence was associated with decreased MACCEs (OR, 0.75; 95% CI, 0.57-0.95), cardiovascular events (OR, 0.66; 95% CI, 0.46-0.93), and 30-day mortality (OR, 0.74; 95% CI, 0.53-0.98). Adherence to the revised SCIP-BB measure was not associated with increased cerebrovascular events (OR, 1.22; 95% CI, 0.62 2.38). CONCLUSIONS AND RELEVANCE: Adherence to the original SCIP-BB measure was associated with increased cerebrovascular events but not improved cardiovascular event outcomes. beta-Blocker continuation consistent with the revised SCIP-BB measure is associated with reduced MACCEs, cardiovascular events, and 30-day mortality. These data provide a cautionary tale of implementing performance measures before they have been rigorously tested. Although the observed associations between adherence to the revised SCIP-BB measure and outcomes are promising, they should be evaluated in the postimplementation period. PMID- 25141796 TI - Characterization of a Corynebacterium glutamicum dnaB mutant that shows temperature-sensitive growth and mini-cell formation. AB - Corynebacterium glutamicum is known to perform a unique form of cell division called post-fission snapping division. In order to investigate the mechanism of cell division of this bacterium, we isolated temperature-sensitive mutants from C. glutamicum wild-type strain ATCC 31831, and found that one of them, M45, produced high frequencies of mini-cells with no nucleoids. Cell pairs composed of an elongated cell, with one nucleoid, connected to a mini-cell, with no nucleoids, were occasionally observed. The temperature sensitivity and mini-cell formation of M45 was complemented by a 2-kb DraI-EcoRI fragment derived from the ATCC 31831 chromosomal DNA, which carried a dnaB homolog encoding a replicative DNA helicase. DNA sequence analysis revealed that M45 carried a missense mutation in the dnaB gene, which caused a substitution of Thr364 to Ile. Microscopic observation after 4',6-diamidino-2-phenylindole staining revealed that the DNA content of single cells was decreased by culturing at the restrictive temperature, suggesting that the mutation affects chromosomal replication. These results suggest that the C. glutamicum dnaB mutant performs an asymmetric cell division even after DNA replication is inhibited, which results in the production of mini-cells. PMID- 25141797 TI - Proteomic profiling of Botrytis cinerea conidial germination. AB - Botrytis cinerea is one of the most relevant plant pathogenic fungi. The first step during its infection process is the germination of the conidia. Here, we report on the first proteome analysis during the germination of B. cinerea conidia, where 204 spots showed significant differences in their accumulation between ungerminated and germinated conidia by two-dimensional polyacrylamide gel electrophoresis and qPCR. The identified proteins were grouped by gene ontology revealing that the infective tools are mainly preformed inside the ungerminated conidia allowing a quick fungal development at the early stages of conidial germination. From 118 identified spots, several virulence factors have been identified while proteins, such as mannitol-1-phosphate dehydrogenase, 6,7 dimethyl-8-ribityllumazine synthase or uracil phosphoribosyltransferase, have been disclosed as a new potential virulence factors in botrytis whose role in pathogenicity needs to be studied to gain new insights about the role of these proteins as therapeutic targets and virulence factors. PMID- 25141798 TI - Structural modifications of dicationic acetylcholinesterase reactivators studied under ion-pairing mechanism in reversed-phase liquid chromatography. AB - A study focused on the chromatographic behavior of several acetylcholinesterase reactivators under ion-pairing mechanism is reported. Among these reactivators, dicationic oximes and carbamoyl-based pyridinium congeners were studied, which form ion pairs with alkylsulfonate anions. This mechanism was studied for some major experimental parameters, such as the chain length of the ion-pairing agent added to the aqueous phase, its concentration, temperature, and nature of the organic modifier from mobile phase. Retention data showed one or two possibilities of forming ion pairs and the tautomerism of the studied reactivators, for different pH values of the aqueous component. Double sigmoid shapes were obtained for the studied compounds for the dependence between retention factor and pH, indicating the possibility of one or two tautomeric equilibria: at pH close to 7 these compounds are not stable as dicationic species and they participate in the retention process as nitroso forms, which are not able to form ion pairs with alkylsulfonates. The dependences of the retention factor on the organic modifier content from mobile phase were linear. Two complementary theoretical models were used to explain the functional dependences for the retention data on the experimental parameters. PMID- 25141799 TI - Perovskite fever. PMID- 25141800 TI - The light and shade of perovskite solar cells. PMID- 25141806 TI - Oxide heterostructures: Atoms on the move. PMID- 25141807 TI - Perovskite solar cells: Continuing to soar. PMID- 25141808 TI - Chiral plasmonic nanostructures: Twisted by DNA. PMID- 25141809 TI - Acoustic metamaterials: Nearly perfect sound absorbers. PMID- 25141810 TI - Self-healing polymers: Sticky when wet. PMID- 25141811 TI - Material witness: Yoghurt under stress. PMID- 25141812 TI - Superhydrophobic bull's-eye for surface-enhanced Raman scattering. AB - We present a micro-patterned silicon structure that enables the preparation of a substrate for surface-enhanced Raman scattering (SERS) and pre-concentration of the analyte molecules. The structure is designed to produce a hydrophobicity gradient. As a result, a water droplet placed on it will remain centred on the structure as it dries, enabling delivery of materials to its centre. The structure is therefore referred to as a superhydrophobic bull's-eye. A water droplet containing gold colloids placed on it dries to produce a cluster at the bull's-eye centre. A second water droplet placed on it, this time containing analyte molecules, dries such that the molecules are delivered to the gold colloid cluster. We demonstrate the detection of molecules at low concentrations (Rhodamine 6G at 10(-15) M) from small droplets. PMID- 25141813 TI - Ebola vaccination: if not now, when? PMID- 25141815 TI - Antidiabetic activity of Piper auritum leaves in streptozotocin-induced diabetic rat, beneficial effect on advanced glycation endproduct. AB - OBJECTIVE: To investigate the effect of hypoglycaemic, hypolipidemic, oxidative stress, insulin resistance and advanced glycation endproducts (AGEs) formation of hexane extract from Piper auritum. METHODS: The streptozotocin (STZ)-induced diabetic Wistar rats were treated with the hexane extract from Piper auritum leaves for 28 days and a set of biochemical parameters were studied including glucose level, total cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The liver function was observed by determining glucose-6 phosphatase, glucokinase and hexokinase activities, and the effect of the hexane extract on insulin level and protein glycation. RESULTS: There was a significant increase in blood glucose level (P<0.05) in diabetic rats after 24 h of STZ injection. There was a significantly decreased in blood glucose in diabetic rats with hexane extract treatment (P<0.05). The serum biochemical parameters, hepatic enzymes, thiobarbituric acid reactive substances, glycosylated hemoglobin, AGEs, and insulin level (P<0.01 or P<0.05) were restored to normal levels in STZ diabetic rats treated with hexane extract. CONCLUSION: The hexane extract from Piper auritum leaves can efficiently inhibit insulin resistance, AGEs formation, improvement of renal function, lipid abnormalities and oxidative stress, indicating that its therapeutic properties may be due to the interaction of hexane extract components with multiple targets involved in diabetes pathogenesis. PMID- 25141814 TI - Neosomes of tungid fleas on wild and domestic animals. AB - Tunga is the most specialized genus among the Siphonaptera because adult females penetrate into the skin of their hosts and, after mating and fertilization, undergo hypertrophy, forming an enlarged structure known as the neosome. In humans and other warm-blooded animals, neosomes cause tungiasis, which arises due to the action of opportunistic agents. Although its effects on humans and domestic animals are well described in the literature, little is known about the impact of tungiasis on wild animals. This review focuses on the morphology, taxonomy, geographical distribution, hosts, prevalence, sites of attachment, and impact of tungid neosomes on wild and domestic animals. Because neosomes are the most characteristic form of the genus Tunga and also the form most frequently found in hosts, they are here differentiated and illustrated to aid in the identification of the 13 currently known species. Perspectives for future studies regarding the possibility of discovering other sand flea species, adaptation to new hosts, and the transfer of tungids between hosts in natural and modified habitats are also presented. PMID- 25141816 TI - Evaluation of in vitro enzymatic and non-enzymatic antioxidant properites of leaf extract from Alpinia Purpurata (Vieill.) K. Schum. AB - OBJECTIVE: To evaluate the enzymatic and non-enzymatic antioxidants of leaf extract from Alpinia purpurata. METHODS: One gram of fresh leaf of Alpinia purpurata was grinded in 2 mL of 50% ethanol and centrifuged at 10,000*g at 4 degrees C for 10 min. The supernatant obtained was used within 4 h for various enzymatic antioxidants assays like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), ascorbate oxidase, peroxidase, polyphenol oxidase (PPO) and non-enzymatic antioxidants such as vitamin C, total reduced glutathione (TRG) and lipid peroxidation (LPO). RESULTS: The leaf extract of Alpinia purpurata possess antioxidants like vitamin C 472.92+/-6.80 MUg/mg protein, GST 372.11+/-5.70 MUmol of 1-chloro 2,4 dinitrobenzene (CDNB)-reduced glutathione (GSH) conjugate formed/min/mg protein, GPx 281.69+/-6.43 MUg of glutathione oxidized/min/mg protein, peroxidases 173.12+/-9.40 MUmol/g tissue, TRG 75.27+/-3.55 MUg/mg protein, SOD 58.03+/-2.11 U/mg protein, CAT 46.70+/-2.35 MUmol of H2O2 consumed/min/mg protein in high amount whereas ascorbate oxidase 17.41+/-2.46 U/g tissue, LPO 2.71+/-0.14 nmol/L of malondialdehyde formed/min/mg protein and PPO 1.14+/-0.11 MUmol/g tissue in moderate amount. CONCLUSION: Alpinia purpurata has the potential to scavenge the free radicals and protect against oxidative stress causing diseases. In future, Alpinia purpurata may serve as a good pharmacotherapeutic agent. PMID- 25141817 TI - Effect of Schisandra chinensis on interleukins, glucose metabolism, and pituitary adrenal and gonadal axis in rats under strenuous swimming exercise. AB - OBJECTIVE: To investigate the effect of Chinese medicine (CM) Schisandra chinensis on interleukin (IL), glucose metabolism, and pituitary-adrenal and gonadal axis of rats after strenuous navigation and exercise. METHODS: A total of 45 Sprague-Dawley rats were randomized into the quiet control group, the stress group, and the CM group (15 in each group). The CM group received 2.5 g/kg of Schisandra chinensis twice per day for one week before modeling. Except the quiet controls, rats were trained using the Bedford mode for 10 days. On the 11th day, they performed 3 h of stressful experimental navigation and 3 h of strenuous treadmill exercise. The levels of serum testosterone (T), cortisol (CORT), luteinizing hormone (LH), IL-1, IL-2, and IL-6 were tested by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The adrenal cortex ultrastructure was observed using electron microscopy. RESULTS: Compared with the quiet control group, after navigation and strenuous exercise, blood glucose was increased, and T level was decreased in the stress group (both P<0.01). The blood glucose, CORT, IL-1 and IL-2 levels were significantly reduced in the CM group (P<0.05 or P<0.01) as compared with the stress group. Electron microscopy revealed that the rats in the CM group had a smaller decrease in adrenal intracellular lipid droplets and higher levels of apoptosis than those in the stress group. CONCLUSIONS: Schisandra chinensis can reduce serum CORT and blood glucose levels in stressed rats. It appears to protect the cell structure of the adrenal cortex, and offset the negative effects of psychological stress and strenuous exercise related to immune dysfunction. Schisandra chinensis plays a regulatory role in immune function, and can decrease the influence of stress in rats. PMID- 25141818 TI - Effect of p27 gene combined with Pientzehuang ([characters: see text]) on tumor growth in osteosarcoma-bearing nude mice. AB - OBJECTIVE: To observe the effect of p27 gene recombinant adenovirus combined with Chinese medicine Pientzehuang ([characters: see text]) on the growth of xenografted human osteosarcoma in nude mice. METHODS: Tissue transplantation was used to construct the orthotopic model of human osteosarcoma Saos-2 cell in nude mice. Thirty tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group: blank control group (model of osteosarcoma), empty vector group (recombinant adeno-associated virus-multiple cloning site), Pientzehuang group, p27 gene group and combined treatment group (p27 gene combined with Pientzehuang). The effect of combined treatment on human osteosarcoma was analyzed through the tumor formation, tumor volume and inhibition rate of tumor growth. The expression of p27 was measured by immunohistochemical staining and Western blot. RESULTS: The orthotopic model of osteosarcoma in nude mice was successfully constructed. The general appearance of tumor-bearing nude mice in Pientzehuang and p27 gene groups was markedly improved compared with the blank control group; and in the combined treatment group it was significantly improved compared with the Pientzehuang and p27 gene groups. The tumor growth in the Pientzehuang and p27 gene groups was significantly inhibited compared with the blank control group P<0.05); while in the combined treatment group it was markedly inhibited compared with the Pientzehuang and p27 gene groups (P<0.05). The rates of tumor growth inhibition were 34.1%, 56.5% and 63.8% in the Pientzehuang, p27 gene and combined treatment groups, respectively. Meanwhile, the protein expression of p27 gene in the p27 gene group was significantly increased compared with the blank control group (P<0.05); and it was significantly increased in the combined treatment group compared with the p27 gene and Pientzehuang groups (P<0.05). CONCLUSION: p27 gene introduced by adenovirus combined with Pientzehuang can inhibit the growth of human osteosarcoma cell Saos-2 in nude mice. PMID- 25141819 TI - NACP 2014 and the Turku PET symposium: the interaction between therapy and imaging. PMID- 25141820 TI - Study protocol: the JEU cohort study--transversal multiaxial evaluation and 5 year follow-up of a cohort of French gamblers. AB - BACKGROUND: There is abundant literature on how to distinguish problem gambling (PG) from social gambling, but there are very few studies of the long-term evolution of gambling practice. As a consequence, the correlates of key state changes in the gambling trajectory are still unknown. The objective of the JEU cohort study is to identify the determinants of key state changes in the gambling practice, such as the emergence of a gambling problem, natural recovery from a gambling problem, resolution of a gambling problem with intermediate care intervention, relapses or care recourse. METHODS/DESIGN: The present study was designed to overcome the limitations of previous cohort study on PG. Indeed, this longitudinal case-control cohort is the first which plans to recruit enough participants from different initial gambling severity levels to observe these rare changes. In particular, we plan to recruit three groups of gamblers: non problem gamblers, problem gamblers without treatment and problem gamblers seeking treatment.Recruitment takes place in various gambling places, through the press and in care centers. Cohort participants are gamblers of both sexes who reported gambling on at least one occasion in the previous year and who were aged between 18 and 65. They were assessed through a structured clinical interview and self assessment questionnaires at baseline and then once a year for five years. Data collection comprises sociodemographic characteristics, gambling habits (including gambling trajectory), the PG section of the DSM-IV, the South Oaks Gambling Screen, the Gambling Attitudes and Beliefs Survey - 23, the Mini International Neuropsychiatric Interview, the Wender-Utah Rating Scale-Child, the Adult ADHD Self-report Scale, somatic comorbidities (especially current treatment and Parkinson disease) and the Temperament and Character Inventory - 125. DISCUSSION: The JEU cohort study is the first study which proposes to identify the predictive factors of key state changes in gambling practice. This is the first case-control cohort on gambling which mixes non-problem gamblers, problem gamblers without treatment and problem gamblers seeking treatment in almost equal proportions. This work may help providing a fresh perspective on the etiology of pathological gambling, which may provide support for future research, care and preventive actions. TRIAL REGISTRATION: (ClinicalTrials.gov): NCT01207674. PMID- 25141821 TI - Recurrent mutations of NOTCH genes in follicular lymphoma identify a distinctive subset of tumours. AB - Follicular lymphoma (FL) is one of the most common malignant lymphomas. The t(14;18)(q32;q21) translocation is found in about 80% of cases and plays an important role in lymphomagenesis. However, the molecular mechanisms involved in the development and transformation of this lymphoma are not fully understood. Gain-of-function mutations of NOTCH1 or NOTCH2 have recently been reported in several B cell lymphoid neoplasms but the role of these mutations in FL is not known. In this study we investigated the mutational status of these genes in 112 FLs. NOTCH1 and NOTCH2 mutations were identified in five and two cases, respectively (total 7/112, 6.3%). All mutations predicted for truncated protein in the PEST domain and were identical to those identified in other B cell lymphoid neoplasms. NOTCH-mutated FL cases were characterized by lower frequency of t(14;18) (14% versus 69%, p = 0.01), higher incidence of splenic involvement (71% versus 25%, p = 0.02) and female predominance (100% versus 55%, p = 0.04). A diffuse large B cell lymphoma (DLBCL) component was more frequently identified in NOTCH-mutated FL than in wild-type cases (57% versus 18%, p = 0.03). These results indicate that NOTCH mutations are uncommon in FL but may occur in a subset of cases with distinctive, characteristic, clinicopathological features. PMID- 25141823 TI - Strong topographic sheltering effects lead to spatially complex treeline advance and increased forest density in a subtropical mountain region. AB - Altitudinal treelines are typically temperature limited such that increasing temperatures linked to global climate change are causing upslope shifts of treelines worldwide. While such elevational increases are readily predicted based on shifting isotherms, at the regional level the realized response is often much more complex, with topography and local environmental conditions playing an important modifying role. Here, we used repeated aerial photographs in combination with forest inventory data to investigate changes in treeline position in the Central Mountain Range of Taiwan over the last 60 years. A highly spatially variable upslope advance of treeline was identified in which topography is a major driver of both treeline form and advance. The changes in treeline position that we observed occurred alongside substantial increases in forest density, and lead to a large increase in overall forest area. These changes will have a significant impact on carbon stocking in the high altitude zone, while the concomitant decrease in alpine grassland area is likely to have negative implications for alpine species. The complex and spatially variable changes that we report highlight the necessity for considering local factors such as topography when attempting to predict species distributional responses to warming climate. PMID- 25141822 TI - Osteoporosis in the jawbones: a correlative factor of primary trigeminal neuralgia? AB - Trigeminal neuralgia (TN), a neuropathic disorder of one or both of the trigeminal nerves, occurs most often in people over age 50. Extreme, sporadic, sudden burning or shock-like face pain in common activities greatly lowers quality of life. The precise cause of primary TN remains unknown, but it may be caused by vascular pressing on the trigeminal nerve in its root entry zone (REZ), demyelinization of trigeminal sensory fibers, or jawbone cavity. Accordingly, many treatments carry risks of adverse effects, recurrence, and complications. TN and osteoporosis have similar high-risk populations and a common influential factor - emotional stress - is also closed related to primary TN for calcitonin gene-related peptide and calcitonin. Jawbone cavity, which is a possible pathogenesis of TN, may be another form of jawbone osteoporosis. Therefore, we hypothesized that osteoporosis in jaws could be a correlative factor of primary TN. If this hypothesis is verified, it may suggest specific new ideas for the early preventive treatment of primary TN. PMID- 25141824 TI - Functional repetitive sequences and fragile sites in chromosomes of Lolium perenne L. AB - Lolium perenne is considered a high-quality forage widely used in temperate regions to meet the shortage of forage during the winter. In this species, some peculiarities related to cytogenetic aspects have already been described, as the variability in number and position of 45S ribosomal DNA (rDNA) sites and the expression of fragile sites, which require further studies to support the understanding of their causes and consequences. In this way, this study aimed to evaluate the relationship between the expression of fragile sites and functional repetitive sequences (rDNA and telomeric) in chromosomes of diploid and polyploid cultivars of L. perenne. The techniques of FISH, Ag-NOR and fluorescence banding were used to assess the distribution of sites of 45S rDNA, 5S, telomeric sequences, and the transcriptional activity of the 45S ribosomal genes and the distribution of AT- and/or GC-rich sequences in L. perenne, respectively. There was variability in the number and location of 45S rDNA sites, which was not observed for 5S rDNA sites. One of the genotypes showed two 45S rDNA sites on the same chromosome, located in different chromosome arms. Breaks and gaps were found in 45S rDNA sites in most metaphases evaluated for both cultivars. Telomeric sequences were not detected at the end of the chromosomal fragments corresponding to the location of breaks at 45S sites. Apparently, the transcriptional activity was modified in fragile sites. Variation in the number and size of nucleoli, nucleolar fusions and dissociations were observed. All CMA(+) bands were colocalized with the 45S sites. PMID- 25141827 TI - Direct measurement of interaction forces between charged multilamellar vesicles?. AB - Depletion-attraction induced adhesion of two giant (~ 40 MUm), charged multilamellar vesicles is studied using a new Cantilevered-Capillary Force Apparatus, developed in this laboratory. The specific goal of this work is to investigate the role of dynamics in the adhesion and de-adhesion processes when the vesicles come together or are pulled apart at a constant velocity. Hydrodynamic effects are found to play an important role in the adhesion and separation of vesicles at the velocities that are studied. Specifically, a period of hydrodynamically controlled drainage of the thin film between vesicles is observed prior to adhesion, and it is shown that the force required to separate a pair of tensed, adhering vesicles increases with increasing separation velocity and membrane tension. It is also shown that the work done to separate the vesicles increases with separation velocity, but exhibits a maximum as the membrane tension is varied. PMID- 25141825 TI - Human genetic disorders of sphingolipid biosynthesis. AB - Monogenic defects of sphingolipid biosynthesis have been recently identified in human patients. These enzyme deficiencies affect the synthesis of sphingolipid precursors, ceramides or complex glycosphingolipids. They are transmitted as autosomal recessive or dominant traits, and their resulting phenotypes often replicate the abnormalities seen in murine models deficient for the corresponding enzymes. In quite good agreement with the known critical roles of sphingolipids in cells from the nervous system and the epidermis, these genetic defects clinically manifest as neurological disorders, including paraplegia, epilepsy or peripheral neuropathies, or present with ichthyosis. The present review summarizes the genetic alterations, biochemical changes and clinical symptoms of this new group of inherited metabolic disorders. Hypotheses regarding the molecular pathophysiology and potential treatments of these diseases are also discussed. PMID- 25141828 TI - CDC Kerala 9: Effectiveness of low intensity home based early intervention for autism spectrum disorder in India. AB - OBJECTIVE: To validate effectiveness of low intensity, home based early intervention (EI) models in autism for countries with low disability resources. METHODS: Fifty-two toddlers and young children were assessed before and after intervention with Childhood Autism Rating Scale, Vineland Social Maturity Scale, and Receptive-Expressive Emergent Language Scale. Developmental and speech therapists helped mothers assemble low-cost training kits based on the developmental age of the child, gave initial training in the basic behavioral technique to address the three autism symptom clusters at home. Follow-up support was given either on a weekly, fortnightly or monthly basis. Most of the children were also placed in play-schools. Data was analyzed using appropriate bivariate and multivariate techniques. RESULTS: There was statistical and clinical amelioration in the severity of autism, with acquisition of social skills and language skills (all P = 0.001) after intervention in children with mild to severe autism. Gender showed a trend in becoming a significant predictor for intervention response. CONCLUSIONS: Low-intensity, home-based EI can be effectively used in situations where there is paucity of disability resources in countries like India, especially in primary-care and community settings. PMID- 25141826 TI - Increased and early lipolysis in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency during fast. AB - Children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. Knowledge on substrate metabolism in children with LCHAD deficiency during fasting is limited. Treatment guidelines differ between centers, both as far as length of fasting periods and need for night feeds are concerned. To increase the understanding of fasting intolerance and improve treatment recommendations, children with LCHAD deficiency were investigated with stable isotope technique, microdialysis, and indirect calometry, in order to assess lipolysis and glucose production during 6 h of fasting. We found an early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia. The rate of glycerol production, reflecting lipolysis, averaged 7.7 +/- 1.6 umol/kg/min, which is higher compared to that of peers. The rate of glucose production was normal for age; 19.6 +/- 3.4 umol/kg/min (3.5 +/- 0.6 mg/kg/min). Resting energy expenditure was also normal, even though the respiratory quotient was increased indicating mainly glucose oxidation. The results show that lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested. PMID- 25141830 TI - The importance of proximity to death in modelling community medication expenditures for older people: evidence from New Zealand. AB - BACKGROUND: Concerns about the long-term sustainability of health care expenditures (HCEs), particularly prescribing expenditures, has become an important policy issue in most developed countries. Previous studies suggest that proximity to death (PTD) has a significant effect on total HCEs, with its exclusion leading to an overestimation of likely growth. There are limited studies of pharmaceutical expenditures in which PTD is taken into account. OBJECTIVE: This study presents an empirical analysis of public medication expenditure on older individuals in New Zealand (NZ). The aim of the study was to examine the individual effects of age and PTD using individual-level data. METHODS: This study uses individual-level dispensing data from 2008/2009 covering the whole population of medication users aged 70 years or older and resident in NZ. A case-control methodology was used to examine individual cost and medication use for a 12-month period for decedents (cases) and survivors (controls). A random effects two-part model, with a Probit and generalized linear model (GLM) was used to explore the effect of age and PTD on expenditures. RESULTS: The impact of PTD on prescription expenditure is not as dramatic as studies reporting on acute and/or long-term care. The 12-month decedent-to-survivor mean expenditure ratio was 1.95; 2.09 for males and 1.82 for females. The additional cost of dying in terms of prescription drugs decreases with age, with those who die at 90 years of age or older consuming fewer drugs on average and having a lower mean expenditure than those who died in their 70s and 80s. The following variables were found to have a decreasing effect on the mean monthly prescription expenditures: a reduction of 2.2 % for each additional year of age, 4.2 % being in the Maori ethnic group, and 7.8 % for Pacific Islanders. Increases in monthly expenditure were associated with being a decedent 32.1-62.6 % (depending on month), being of Asian origin 16.2 %, or being a male 12.6 %. CONCLUSIONS: Given the variance reported between survivors and decedents, future projections should include PTD in their models to improve accuracy. Policies targeted at reducing expenditures should not focus on age but on ensuring appropriate and cost effective prescribing, particularly towards the end of life. PMID- 25141829 TI - Th17-related cytokines contribute to recall-like expansion/effector function of HMBPP-specific Vgamma2Vdelta2 T cells after Mycobacterium tuberculosis infection or vaccination. AB - Whether cytokines can influence the adaptive immune response by antigen-specific gammadelta T cells during infections or vaccinations remains unknown. We previously demonstrated that, during BCG/Mycobacterium tuberculosis (Mtb) infections, Th17-related cytokines markedly upregulated when phosphoantigen specific Vgamma2Vdelta2 T cells expanded. In this study, we examined the involvement of Th17-related cytokines in the recall-like responses of Vgamma2Vdelta2 T cells following Mtb infection or vaccination against TB. Treatment with IL-17A/IL-17F or IL-22 expanded phosphoantigen 4-hydroxy-3-methyl but-enyl pyrophosphate (HMBPP)-stimulated Vgamma2Vdelta2 T cells from BCG vaccinated macaques but not from naive animals, and IL-23 induced greater expansion than the other Th17-related cytokines. Consistently, Mtb infection of macaques also enhanced the ability of IL-17/IL-22 or IL-23 to expand HMBPP stimulated Vgamma2Vdelta2 T cells. When evaluating IL-23 signaling as a prototype, we found that HMBPP/IL-23-expanded Vgamma2Vdelta2 T cells from macaques infected with Mtb or vaccinated with BCG or Listeria DeltaactA prfA* ESAT6/Ag85B produced IL-17, IL-22, IL-2, and IFN-gamma. Interestingly, HMBPP/IL 23-induced production of IFN-gamma in turn facilitated IL-23-induced expansion of HMBPP-activated Vgamma2Vdelta2 T cells. Furthermore, HMBPP/IL-23-induced proliferation of Vgamma2Vdelta2 T cells appeared to require APC contact and involve the conventional and novel protein kinase C signaling pathways. These findings suggest that Th17-related cytokines can contribute to recall-like expansion and effector function of Ag-specific gammadelta T cells after infection or vaccination. PMID- 25141831 TI - Randomized prospective trial comparing two supraglottic airway devices: i-gelTM and LMA-SupremeTM in paralyzed patients. AB - PURPOSE: Many features can influence the choice of a supraglottic airway device (SAD), including ease of insertion, adequate ventilation pressures and lack of adverse effects. The goal of this randomized prospective trial was to compare the performance of the i-gelTM with that of the LMA-SupremeTM. METHODS: One hundred adult patients (American Society of Anesthesiologists I-III) scheduled to undergo elective surgery under general anesthesia were randomized to either an i-gel (n = 50) or an LMA-Supreme (n = 50). The primary objective was to compare ventilation pressures. Secondary objectives included time and number of attempts needed to introduce the device, adverse effects, and repositioning. The endoscopic view of the glottic aperture and the position of the drain tubes in relation to the esophagus were also evaluated. RESULTS: The devices were inserted successfully in 46 (92%) patients in both groups. There was no significant difference in the [mean (SD)] leak pressure [i-gel: 23 (7) cm H2O vs LMA-Supreme: 21 (8) cm H2O; P = 0.14] or peak inspiratory pressure between both devices. Insertion time was shorter with the i-gel than with the LMA-Supreme [19 (7) sec vs 27 (17) sec, respectively; P = 0.003]. The vocal cords were completely visualized more often through the i-gel (70%) than through the LMA-Supreme (50%) (P = 0.007). Esophageal mucosa was easily visualized through the drain port in all but four patients, two patients in each group. There was no difference between groups regarding preoperative or postoperative complications. Postoperative patient discomfort was generally mild and comparable between both devices. CONCLUSION: Both the LMA-Supreme and the i-gel offer similar performance for positive pressure ventilation in paralyzed patients during general anesthesia. The i-gel was associated with a slightly faster insertion time and better fibrescopic visualization of the glottis. This trial was registered at Clinicaltrials.gov: NCT01001078. PMID- 25141832 TI - Association of anesthesia technique for radical prostatectomy with biochemical recurrence: a retrospective cohort study. AB - INTRODUCTION: Anesthesia technique has been associated with cancer outcomes after radical prostatectomy (RP). These studies are limited by variability in surgeon experience, bias in patient selection, and in some cases, sample size. We evaluated the impact of anesthesia technique for RP on biochemical recurrence (BCR) using a large cohort of patients operated on by a single experienced surgeon. METHODS: We retrospectively reviewed data from a prospective institutional oncologic database on 929 patients treated with RP by a single surgeon from 1999-2008. Spinal anesthesia was used for patients from 2002-2006. We compared outcomes of these patients (n = 264) with outcomes of patients who underwent general anesthesia (n = 665) at Memorial Sloan-Kettering Cancer Center from 1999-2001 and 2006-2008. Cox proportional hazards regression was used to assess differences in BCR rates between the anesthesia groups adjusting for differences in postoperative factors related to anesthetic technique and tumour pathologic characteristics associated with BCR after RP. RESULTS: Median follow up among patients free from BCR was 4.6 yr. On multivariable analysis, spinal anesthesia did not independently predict the rate of BCR (hazard ratio = 1.10; 95% confidence interval 0.7 to 1.74; P = 0.7). Independent predictors of BCR were preoperative prostate-specific antigen (PSA), pathologic Gleason grade, extracapsular extension, and seminal vesicle invasion. CONCLUSIONS: We did not find an association between anesthesia technique and disease recurrence in men with prostate cancer treated with RP. Anesthesia technique is unlikely to alter disease recurrence following RP independent of surgical and pathological factors. PMID- 25141833 TI - Lung re-inflation after one-lung ventilation for thoracic surgery: importance of clamping the dependent lung. PMID- 25141835 TI - Obesogenic television food advertising to children in Malaysia: sociocultural variations. AB - BACKGROUND: Food advertising on television (TV) is well known to influence children's purchasing requests and models negative food habits in Western countries. Advertising of unhealthy foods is a contributor to the obesogenic environment that is a key driver of rising rates of childhood obesity. Children in developing countries are more at risk of being targeted by such advertising, as there is a huge potential for market growth of unhealthy foods concomitant with poor regulatory infrastructure. Further, in developing countries with multi ethnic societies, information is scarce on the nature of TV advertising targeting children. OBJECTIVES: To measure exposure and power of TV food marketing to children on popular multi-ethnic TV stations in Malaysia. DESIGN: Ethnic-specific popular TV channels were identified using industry data. TV transmissions were recorded for each channel from November 2012 to August 2013 (16 hr/day) for randomly selected weekdays and weekend days during normal days and repeated during school holidays (n=88 days). Coded food/beverage advertisements were grouped into core (healthy), non-core (non-healthy), or miscellaneous (unclassified) food categories. Peak viewing time (PVT) and persuasive marketing techniques were identified. RESULTS: Non-core foods were predominant in TV food advertising, and rates were greater during school holidays compared to normal days (3.51 vs 1.93 food ads/hr/channel, p<0.001). During normal days' PVT, the ratio of non-core to core food advertising was higher (3.25 food ads/hr/channel), and this more than trebled during school holidays to 10.25 food ads/hr/channel. Popular channels for Indian children had the lowest rate of food advertising relative to other ethnic groups. However, sugary drinks remained a popular non core product advertised across all broadcast periods and channels. Notably, promotional characters doubled for non-core foods during school holidays compared to normal days (1.91 vs 0.93 food ads/hr/channel, p<0.001). CONCLUSIONS: This study highlights non-core food advertising, and predominantly sugary drinks are commonly screened on Malaysian TV channels. The majority of these sugary drinks were advertised by multinational companies, and this observation warrants regulatory attention. PMID- 25141837 TI - Long-term inhibition of miR-21 leads to reduction of obesity in db/db mice. AB - OBJECTIVE: To assess the effect of long-term pharmacological inhibition of miR-21 in a model of metabolic syndrome and obesity. METHODS: Aged db/db mice were treated with locked nucleic acid-modified anti-miRs directed against miR-21 (LNA 21), control LNAs or PBS for 18 weeks. Cardiac function was assessed by echocardiography and the effect on body weight and white adipose tissue (WAT) was evaluated. RESULTS: MiR-21 expression was efficiently inhibited in the heart and WAT with no apparent liver toxicity or deterioration of kidney function. MiR-21 inhibition had no effect on cardiac hypertrophy as well as systolic and diastolic cardiac functions. However, levels of cardiac collagen 1 were modestly reduced in LNA-21 treated mice. MiR-21 inhibition reduced body weight, as well as adipocyte size and serum triglycerides were significantly decreased. The miR-21 targets TGFbeta-receptor 2 (TGFBR2) and phosphatase and tensin homolog (PTEN) were derepressed in WAT of LNA-21 treated mice and Sprouty1 and 2 were increased after miR-21 inhibition. CONCLUSIONS: Long-term treatment with LNA-21 is safe and efficiently suppresses miR-21 expression. Cardiac function was not affected. LNA 21 treatment led to a significant weight loss and reduces adipocyte size as well as derepression of the targets TGFRB2, PTEN, and Sprouty1 and 2. PMID- 25141838 TI - Analysis of aromatic acids by nonaqueous capillary electrophoresis with ionic liquid electrolytes. AB - The separation of six kinds of aromatic acids by CZE with 1-ethyl-3 methylimidazolium chloride (EMIMCl) and 1-ethyl-3-methylimidazolium hydrogen sulfate (EMIMHSO4 ), two kinds of ionic liquids (ILs) as background electrolytes, and acetonitrile as solvent were investigated. The six kinds of aromatic acids can be separated under positive voltage with low IL concentration with either of the two ILs and separation with EMIMHSO4 is better in consideration of peak shapes and separation efficiency. But the migration order is different when the IL is different. Under negative voltage with high IL concentration, the six analytes can be separated with EMIMCl as background electrolytes and the migration order of the analytes is opposite to those with low concentration of EMIMCl as background electrolyte. The separations are based on the combination effects of heteroconjugation between the anions and cations in the ILs and the analytes, of which the heteroconjugation between the anions in the ILs and the analytes plays a dominant role. The heteroconjugation between the anions of the ILs and analytes is proton sensitive and only a very small amount of proticsolvents added into the electrolyte solution can harm the separation. When EMIMCl concentration is high, the heteroconjugation between the IL anions and the proton in the analytes make the effective mobility of the analytes much higher than the EOF and their migration direction reversed. Finally, the six aromatic acids in water samples were analyzed by nonaqueous CE with low concentration of EMIMHSO4 as background electrolytes with satisfactory results. PMID- 25141839 TI - TBHP-induced oxidative stress alters microRNAs expression in mouse testis. AB - PURPOSE: Reactive oxygen species (ROS) and oxidative stress is one of the main reasons of male infertility. MicroRNAs (miRNAs) regulate multiple intracellular processes. Alterations in miRNAs expression may occur in different conditions and diseases. In this study, the effect of oxidative stress induced by tertiary-butyl hydroperoxide (TBHP) on the expression of candidate miRNAs in mouse testis was investigated. METHODS: After determining median lethal dose (LD50), TBHP was intraperitoneally (ip) injected at the dilution of 1:10 LD50 into the adult male mice for 2 weeks, and then testis tissues were removed in order to assay the ROS level. Total RNA was extracted and the expression of five miRNAs was quantified by reverse transcription-real time polymerase chain reaction (RT-qPCR). RESULTS: The flow cytometry analysis showed a significant increase in ROS level in testis. The expression of three out of five selected miRNAs, including miR-34a, miR-181b and miR-122a, showed some degrees of changes following exposure to oxidative stress. These miRNAs are involved in antioxidant responses, inflammation pathway and spermatogenesis arrest. CONCLUSIONS: In conclusion, TBHP alters the miRNA expression profile of testis which might play a potential role in oxidative and antioxidative responses and spermatogenesis. PMID- 25141840 TI - Efficacy of cryopreservation of embryos generated by intracytoplasmic sperm injection with spermatozoa from frozen testicular tissue. AB - PURPOSE: To evaluate the viability of frozen embryos generated by intracytoplasmic sperm injection (ICSI) with frozen testicular spermatozoa. METHODS: A total of 68 fresh embryo transfer (ET) cycles and 85 subsequent frozen thawed ET (FET) cycles were grouped according to the source of spermatozoa: fresh testicular spermatozoa (TESE) or frozen-thawed testicular spermatozoa (t-TESE). RESULTS: There were no significant differences in the age of female patients, number of oocytes, or fertilization rates in fresh ET cycles with TESE (TESE fresh ET) versus t-TESE (t-TESE-fresh ET). The rate of embryo survival after thawing (95.7 % vs. 94.0 %) was similar in frozen ET cycles (FET) with TESE (TESE FET) and with t-TESE (t-TESE-FET). While there were significant differences in the proportion of good quality embryos, no statistical differences were found in the pregnancy or clinical abortion rates between the two groups. Moreover, delivery rates were not significantly different. CONCLUSIONS: Although the proportion of good quality embryos was affected by cryopreservation of testicular tissue, embryo survival rate was not. As well, subsequent pregnancy could be achieved successfully via t-TESE-FET cycles. Therefore, FET is not affected by the cryopreservation of testicular tissue, and avoids further oocyte retrieval and TESE procedures. PMID- 25141841 TI - Expression profile of developmentally important genes between hand-made cloned buffalo embryos produced from reprogramming of donor cell with oocytes extract and selection of recipient cytoplast through brilliant cresyl blue staining and in vitro fertilized embryos. AB - PURPOSE: To compare the expression profile of developmentally important genes between hand-made cloned buffalo embryos produced from reprogramming of donor cell with oocyte extracts and selection of recipient cytoplast through brilliant cresyl blue staining and in vitro fertilized (IVF) embryos. METHODS: Hand-made cloned embryos were produced using oocyte extracts treated donor cells and brilliant cresyl blue (BCB) stained recipient cytoplasts. IVF embryos were produced by culturing 15-20 COCs in BO capacitated sperms from frozen thawed buffalo semen and the mRNA expression patterns of genes implicated in metabolism (GLUT1), pluripotency (OCT4), DNA methylation (DNMT1), pro- apoptosis (BAX) and anti-apoptosis (BCL2) were evaluated at 8- to16- cell stage embryos. RESULTS: A significantly (P < 0.05) higher number of 8- to16- cell and blastocyst stages (73.9 %, 32.8 %, respectively) were reported in hand-made cloning (HMC) as compared to in vitro fertilization (49.2 %, 24.2 %, respectively). The amount of RNA recovered from 8- to 16- cell embryos of HMC and in vitro fertilization did not appear to be influenced by the method of embryo generation (3.76 +/- 0.61 and 3.82 +/- 0.62 ng/MUl for HMC and in vitro fertilization embryos, respectively). There were no differences in the expression of the mRNA transcripts of genes (GLUT1, OCT4, DNMT1, BAX and BCL2) were analysed by real-time PCR between hand made cloned and IVF embryos. CONCLUSIONS: Pre-treatment of donor cells with oocyte extracts and selection of developmentally competent oocytes through BCB staining for recipient cytoplast preparations may enhance expression of developmentally important genes GLUT1, OCT4, DNMT1, BAX, and BCL2 in hand-made cloned embryos at levels similar to IVF counterparts. These results also support the notion that if developmental differences observed in HMC and in vitro fertilization produced foetuses and neonates are the results of aberrant gene expression during the pre-implantation stage, those differences in expression are subtle or appear after the maternal to zygotic transition stage of development. PMID- 25141842 TI - What is the frequency of nerve injuries associated with acetabular fractures? AB - BACKGROUND: Acetabular fractures and surgical interventions used to treat them can result in nerve injuries. To date, only small case studies have tried to explore the frequency of nerve injuries and their association with patient and treatment characteristics. High-quality data on the risk of traumatic and iatrogenic nerve lesions and their epidemiology in relation to different fracture types and surgical approaches are lacking. QUESTIONS/PURPOSES: The purpose of this study was to determine (1) the proportion of patients who develop nerve injuries after acetabular fracture; (2) which fracture type(s) are associated with increased nerve injury risk; and (3) which surgical approach was associated with the highest proportion of patients developing nerve injuries using data from the German Pelvic Trauma Registry. Two secondary aims were (4) to assess hospital volume-nerve-injury relationship; and (5) internal data validity. METHODS: Between March 2001 and June 2012, 2236 patients with acetabular fractures were entered into a prospectively maintained registry from 29 hospitals; of those, 2073 (92.7%) had complete records on the endpoints of interest in this retrospective study and were analyzed. The neurological status in these patients was captured at their admission and at the discharge. A total of 1395 of 2073 (67%) patients underwent surgery, and the proportions of intervention-related and other hospital-acquired nerve injuries were obtained. Overall proportions of patients developing nerve injuries, risk based on fracture type, and risk of surgical approach type were analyzed. RESULTS: The proportion of patients being diagnosed with nerve injuries at hospital admission was 4% (76 of 2073) and at discharge 7% (134 or 2073). Patients with fractures of the "posterior wall" (relative risk [RR], 2.0; 95% confidence interval [CI], 1.4-2.8; p=0.001), "posterior column and posterior wall" (RR, 2.9; CI, 1.6-5.0; p=0.002), and "transverse+posterior wall" fracture (RR, 2.1; CI, 1.3-3.5; p=0.010) were more likely to have nerve injuries at hospital discharge. The proportion of patients with intervention-related nerve injuries and that of patients with other hospital acquired nerve injuries was 2% (24 of 1395 and 46 of 2073, respectively). They both were associated with the Kocher-Langenbeck approach (RR, 3.0; CI, 1.4-6.2; p=0.006; and RR, 2.4; CI, 1.4-4.3; p=0.004, respectively). CONCLUSIONS: Acetabular fractures with the involvement of posterior wall were most commonly accompanied with nerve injuries. The data suggest also that Kocher-Langenbeck approach to the pelvic ring is associated with a higher risk of perioperative nerve injuries. Trauma surgeons should be aware of common nerve injuries, particularly in posterior wall fractures. The results of the study should help provide patients with more exact information on the risk of perioperative nerve injuries in acetabular fractures. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 25141843 TI - Metal artifact reduction sequence MRI abnormalities occur in metal-on polyethylene hips. AB - BACKGROUND: To determine the importance of MRI abnormalities in metal-on-metal (MoM) bearings, it is important to understand the baseline features of this diagnostic tool in conventional metal-on-polyethylene (MoP) bearings. QUESTIONS/PURPOSES: What are the frequency, size, and types of MRI-documented adverse local tissue reactions in asymptomatic patients with MoP bearings? METHODS: We recruited 50 patients 5 years after a MoP total hip arthroplasty from a pool of patients in our joint registry who had a Harris hip score of >90. To be included, patients had to be without pain and have adequate radiographs. Our data set included 50 asymptomatic patients with MoP bearings who underwent a metal artifact reduction sequence MRI. RESULTS: MRI abnormalities were seen in 14 of 50 (28%) asymptomatic patients who were studied. Thirteen of the 14 abnormalities were cystic thin-walled lesions with a mean of 18 cm3 (range, 1-79 cm3). CONCLUSIONS: MRI abnormalities were noted in nearly one-third of asymptomatic patients with MoP bearings. Decisions concerning revision of MoM bearings should not be based on isolated MRI findings because MRI abnormalities are commonly seen regardless of bearing type. A number of factors should determine the need for intervention including pain, mechanical symptoms, abductor weakness, component type, component position, and ion levels as well as MRI findings. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 25141844 TI - Can wear explain the histological variation around metal-on-metal total hips? AB - BACKGROUND: There is a general perception that adverse local tissue reactions in metal-on-metal hip arthroplasties are caused by wear, but the degree to which this is the case remains controversial. QUESTIONS/PURPOSES: To what extent is the magnitude of wear associated with (1) the histological changes; (2) presence of metallosis; and (3) likelihood of pseudotumor formation in the periprosthetic tissues? METHODS: One hundred nineteen metal-on-metal total hip arthroplasties and hip resurfacings were selected from a retrieval collection of over 500 implants (collected between 2004 and 2012) based on the availability of periprosthetic tissues collected during revision, clinical data including presence or absence of pseudotumor or metallosis observed intraoperatively, and wear depth measured using a coordinate measurement machine. Histological features of tissues were scored for aseptic lymphocytic vasculitis-associated lesions (ALVAL). Correlation analysis was performed on the three endpoints of interest. RESULTS: With the sample size available, no association was found between wear magnitude and ALVAL score (rho=-0.092, p=0.423). Median wear depth (ball and cup) was greater in hips with metallosis (137 MUm; range, 8-873 MUm) than in those without (18 MUm; range, 8-174 MUm; p<0.0001). With the numbers available, no statistically significant association between wear depth and pseudotumor formation could be identified; median wear depth was 74 MUm in hips with pseudotumors and 26 MUm in those without (p=0.741). CONCLUSIONS: Wear alone did not explain the histopathological changes in the periprosthetic tissues. A larger sample size and more sensitive outcome variable assessments may have revealed a correlation. However, wear depth has been inconsistently associated with pseudotumor formation, perhaps because some patients with hypersensitivity may develop pseudotumors despite low wear. CLINICAL RELEVANCE: Metal wear alone may not explain the histological reactions and pseudotumors around metal-on-metal hip implants. PMID- 25141845 TI - Experimental Disc Herniation in the Rat Causes Downregulation of Serotonin Receptor 2c in a TNF-dependent Manner. AB - BACKGROUND: During recent decades, the knowledge of the pathophysiology of disc herniation and sciatica has drastically improved. What previously was considered a strict biomechanical process is now considered a more complex interaction between leaked nucleus pulposus and the tissue in the spinal canal. An inflammatory reaction, with tumor necrosis factor (TNF) playing an essential role, has been demonstrated. However, the exact mechanisms of the pathophysiology of disc herniation remain unknown. QUESTIONS/PURPOSES: In this study we use an animal model to investigate (1) if and/or how experimental disc herniation affects gene expression in the early phase (24 hours postsurgery) in the dorsal root ganglion; and (2) if TNF inhibition can reduce any observed changes. METHODS: A rat model of disc herniation was used. Twenty rats were evenly divided into four groups: naive, sham, disc herniation, and disc herniation with TNF inhibition. The dorsal root ganglion of the affected nerve root was harvested 24 hours after surgery and analyzed with a TaqMan Low Density Array((r)) quantitative polymerase chain reaction assay. Gene expression levels in sham were compared with disc herniation to assess question 1 and disc herniation to disc herniation with TNF inhibition to assess question 2. RESULTS: Experimental disc herniation caused a decrease in the expression of the serotonin receptor 2c gene (p = 0.022). TNF inhibition was found to reduce the observed decrease in expression of serotonin receptor 2c (p = 0.037). CONCLUSIONS: Our results suggest that a decrease in the expression of the serotonin receptor 2c gene may contribute to the pathophysiology of disc herniation. Further research on its involvement is warranted. CLINICAL RELEVANCE: This pilot study gives a brief insight into cellular changes that may contribute to the pathophysiology of disc herniation. This knowledge may contribute to the development of more and better treatment options for patients with disc herniation and sciatica. PMID- 25141846 TI - The big to do about "big data". PMID- 25141847 TI - CORR Insights(r): fractures in geriatric mice show decreased callus expansion and bone volume. PMID- 25141848 TI - Vastus lateralis vascularized nerve graft in facial nerve reconstruction: an anatomical cadaveric study and clinical implications. AB - BACKGROUND: The present study investigates the vascular anatomy of the vastus lateralis motor nerve (VLMN) to be used as a vascularized nerve graft in facial nerve reconstruction. We evaluated the maximum length of the nerve that can be included in the flap and its vascular pedicle. In addition, we discuss its adequacy for use in early reconstruction of the facial nerve both as ipsilateral facial nerve reconstruction and as cross-facial nerve graft. METHODS: Five fresh cadavers were used in this study. In all specimens, the VLMN and its vascular pedicle were dissected, photodocumented and measured using calipers. In addition, two vascularized VLMN were injected with a radiopaque contrast and underwent CT angiography and three dimensional reconstructions were scanned to illustrate the vascular supply of the nerve using OsiriX Software. RESULTS: The VLMN was divided into two divisions, an oblique proximal and a descending distal, in 70% of the dissections with a mean maximal length of 8.4 +/- 4.5 cm for the oblique division and 15.03 +/- 3.87 cm for the descending division. The length of the oblique division, when present, was shorter than the length of the descending branch in all specimens. The mean length of the pedicle was 2.93 +/- 1.69 cm, and 3.27 +/- 1.49 cm until crossing the oblique and the descending division of the nerve respectively. The mean caliber of the nerve was 2.4 +/- 0.62 mm. Three dimensional computed tomography angiography demonstrated perfusion throughout the entire VLMN by branches from the descending branch of the lateral femoral circumflex artery which ran parallel to the descending division of the VLMN. Additionally, we observed that technically it was possible to preserve the oblique branch of the VLMN. CONCLUSION: This study confirms that VLMN presents adequate anatomic features to be used as a vascularized nerve graft for facial nerve reconstruction in terms of length, pedicle, and caliber. PMID- 25141849 TI - Glycoproteins identified from heart failure and treatment models. AB - Conduction abnormalities can lead to dyssynchronous contraction, which significantly worsens morbidity and mortality of heart failure. Cardiac resynchronization therapy (CRT) can reverse ventricular remodeling and improve cardiac function. Although the underlying molecular changes are unknown, the use of a canine model of dyssynchronous heart failure (DHF) and CRT has shown that there are global changes across the cardiac proteome. This study determines changes in serum glycoprotein concentration from DHF and CRT compared to normal. We hypothesize that CRT invokes protective or advantageous pathways that can be reflected in the circulating proteome. Two prong discovery approaches were carried out on pooled normal, DHF, and CRT samples composed of individual canine serum to determine the overall protein concentration and the N-linked glycosites of circulating glycoproteins. The level of the glycoproteins was altered in DHF and CRT compared to control sera, with 63 glycopeptides substantially increased in DHF and/or CRT. Among the 32 elevated glycosite-containing peptides in DHF, 13 glycopeptides were reverted to normal level after CRT therapy. We further verify the changes of glycopeptides using label-free LC-MS from individual canine serum. Circulating glycoproteins such as alpha-fetoprotein, alpha-2-macroglobulin, galectin-3-binding protein, and collectin-10 show association to failing heart and CRT treatment model. PMID- 25141851 TI - Is it ethical to hire sherpas when climbing Mount Everest? PMID- 25141850 TI - ICT-based system to predict and prevent falls (iStoppFalls): study protocol for an international multicenter randomized controlled trial. AB - BACKGROUND: Falls are very common, especially in adults aged 65 years and older. Within the current international European Commission's Seventh Framework Program (FP7) project 'iStoppFalls' an Information and Communication Technology (ICT) based system has been developed to regularly assess a person's risk of falling in their own home and to deliver an individual and tailored home-based exercise and education program for fall prevention. The primary aims of iStoppFalls are to assess the feasibility and acceptability of the intervention program, and its effectiveness to improve balance, muscle strength and quality of life in older people. METHODS/DESIGN: This international, multicenter study is designed as a single-blinded, two-group randomized controlled trial. A total of 160 community dwelling older people aged 65 years and older will be recruited in Germany (n = 60), Spain (n = 40), and Australia (n = 60) between November 2013 and May 2014. Participants in the intervention group will conduct a 16-week exercise program using the iStoppFalls system through their television set at home. Participants are encouraged to exercise for a total duration of 180 minutes per week. The training program consists of a variety of balance and strength exercises in the form of video games using exergame technology. Educational material about a healthy lifestyle will be provided to each participant. Final reassessments will be conducted after 16 weeks. The assessments include physical and cognitive tests as well as questionnaires assessing health, fear of falling, quality of life and psychosocial determinants. Falls will be followed up for six months by monthly falls calendars. DISCUSSION: We hypothesize that the regular use of this newly developed ICT-based system for fall prevention at home is feasible for older people. By using the iStoppFalls sensor-based exercise program, older people are expected to improve in balance and strength outcomes. In addition, the exercise training may have a positive impact on quality of life by reducing the risk of falls. Taken together with expected cognitive improvements, the individual approach of the iStoppFalls program may provide an effective model for fall prevention in older people who prefer to exercise at home. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Trial ID: ACTRN12614000096651.International Standard Randomised Controlled Trial Number: ISRCTN15932647. PMID- 25141852 TI - Trypanosoma cruzi transmission in a Colombian Caribbean region suggests that secondary vectors play an important epidemiological role. AB - BACKGROUND: Colombia, as part of The Andean Countries Initiative has given priority to triatomine control programs to eliminate primary (domiciliated) vector species such as Rhodnius prolixus and Triatoma dimidiata. However, recent events of Trypanosoma cruzi transmission in localities where R. prolixus and T. dimidiata are not present suggest that other species are involved in the T. cruzi transmission cycle. METHODS: We studied T. cruzi transmission on Margarita Island, located on the Magdalena River in the Colombian Caribbean region, where a high number of non-domiciliated triatomines infected with T. cruzi inside human dwellings have been observed. A cross-sectional survey including serological studies in humans and parasitological and molecular methods in vectors and reservoirs was conducted. We investigated risk factors for human infection and house infestation, and evaluated the association between abundance of wild triatomines in palm trees (Attalea butyracea) across municipalities, seasons and anthropogenic land use. RESULTS: The T. cruzi seroprevalence rate in humans was 1.7% (13/743) and autochthonous active T. cruzi transmission was detected. The infection risk was associated with the capture of triatomines in human dwellings. Five wild mammal species were infected with T. cruzi, where Didelphis marsupialis was the main reservoir host with an 86.3% (19/22) infection rate. TcIb was the only genotype present among vectors. Triatomine abundance was significantly higher in Ecosystem 2, as well as in the dry season. Despite the absence of triatomine domiciliation in this area, T. cruzi active transmission was registered with a human seroprevalence rate similar to that reported in areas with domesticated R. prolixus. CONCLUSIONS: This study illustrates the importance of secondary and household invading triatomines in Chagas disease epidemiology in the Caribbean lowlands of Colombia. PMID- 25141853 TI - Association between estimated glomerular filtration rate and clinical outcomes in patients with acute ischaemic stroke: results from China National Stroke Registry. AB - BACKGROUND: the impact of estimated glomerular filtration rate (eGFR) on stroke clinical outcomes remains controversial. We examined the association between eGFR and all-cause mortality, recurrent stroke, and stroke disability in patients with acute ischaemic stroke. METHODS: we analysed 8865 patients with acute ischaemic stroke in the China National Stroke Registry (CNSR) between September 2007 and August 2008. Multivariate logistic regression analysis was used to evaluate the association between eGFR and 1-year all-cause mortality, recurrent stroke, and stroke disability. Low eGFR was defined as <45 ml/min/1.73 m(2). RESULTS: of 8865 acute ischaemic stroke patients included in the analysis, eGFR of <45 ml/min/1.73 m(2) occurred in 394 (4.4%), eGFR of 45-59 ml/min/1.73 m(2) in 675 (7.6%), eGFR of 60-89 ml/min/1.73 m(2) in 3533 (39.9%), and eGFR of >=90 ml/min/1.73 m(2) in 4263 (48.1%) at baseline. Patients with reduced renal function were more likely to die, experience recurrent stroke or have stroke disability than patients with preserved renal function. After adjusting for both demographic and clinical risk factors, an eGFR of <45 ml/min/1.73 m(2) was independently associated with 1-year all-cause mortality (OR: 2.65; 95% CI: 1.95-3.59) and recurrent stroke (OR: 1.97; 95% CI: 1.51-2.56) but not for stroke disability defined as modified Rankin Score of 2-6 (OR: 1.26; 95% CI: 0.95-1.67). These results were consistent in stratified analyses by age, diabetes or hypertension. CONCLUSIONS: a low eGFR was associated with increased risks of all-cause mortality and recurrent stroke independent of the traditional vascular risk factors in Chinese stroke patients. PMID- 25141854 TI - Partner notification among men who have sex with men and heterosexuals with STI/HIV: different outcomes and challenges. AB - Partner notification effectiveness among index clients diagnosed with HIV, syphilis and/or gonorrhoea at sexually transmitted infection (STI) clinics was evaluated between 2010 and 2012. We explored percentages of identifiable, notified and tested partners by sexual preference and gender. Partner notification trends were studied using the national STI database. Men who have sex with men (n = 304), heterosexual men (n = 33) and women (n = 35) reported, respectively, 6.7, 3.8 and 2.3 partners per index. Percentages of identifiable partners differed between groups (men who have sex with men: 46%, heterosexual men: 63%, women: 87%, p < 0.001). The percentage of notified partners (of those identifiable) was lowest for heterosexual men (76%; men who have sex with men: 92%; women: 83%; p < 0.001). STI positivity rates among notified partners were high: 33%-50% depending on sexual preference. Among men who have sex with men, having HIV was associated with not notifying all identifiable partners. Percentages of notified clients at STI clinics increased between 2010 and 2012: from 13% to 19% among men who have sex with men, from 13% to 18% among heterosexual men and from 8% to 11% among women (p < 0.001 for all groups). The percentage of STI/HIV detected through partner notification increased among men who have sex with men (from 22% to 30%) and women (from 25% to 29%; p < 0.001). Unidentifiable partners among men who have sex with men, lower partner notification effectiveness for HIV and the relative large proportion of heterosexual men not notifying their partners appear to be important partner notification challenges. PMID- 25141855 TI - Is tretinoin still a key agent for photoaging management? AB - BACKGROUND & SCOPE OF THE REVIEW: This review focuses on the UV radiation effects on skin, emphasizing the photoaging process, and the photoprotection conferred by tretinoin (all-trans retinoic acid or ATRA). Tretinoin is still the best tested retinoid to reverse photoaged skin. MAJOR CONCLUSIONS: Tretinoin can be used for photoaging treatment or combined treatment by different mechanisms. It binds to and activates retinoic acid receptors, inducing changes in gene expression that leads to cell differentiation, decreased cell proliferation, and inhibition of tumourigenesis. It has been demonstrated that photoaging resulting from UV-B radiation can be treated by retinoid formulations. Pretreatment of human skin with tretinoin blocks dermal matrix degradation followed by sun exposure, inhibiting the induction of the activated protein-1 (AP-1) transcription factor and AP-1 regulated matrix-degrading metalloproteinases. GENERAL SIGNIFICANCE AND INTEREST: Tretinoin should be considered as a key factor as it is the most potent and best-studied retinoid. In addition, the development of advanced drug delivery systems, especially novel nanoformulations, has contributed to overpass some technical drawbacks besides the skin irritation potential. The triple combination of tretinoin, hydroquinone and corticosteroids is still considered the gold standard for melasma. Although there are other novel therapeutic approaches, more high-quality clinical trials are still needed. PMID- 25141856 TI - Ethanol sclerotherapy of rectal venous abnormalities in Klippel-Trenaunay syndrome. AB - Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder characterized by the triad of capillary malformations, atypical venous malformations and varicosities and bony and/or soft tissue hypertrophy. We present the case of an 18-year-old man with KTS affected by haematochezia secondary to rectal venous malformations that was managed with endoscopic sclerotherapy. In this case, we compared the use of ethanol to phenol as a sclerosant. PMID- 25141857 TI - Potential importance of transition metals in the induction of DNA damage by sperm preparation media. AB - STUDY QUESTION: What are the mechanisms by which the preparation of spermatozoa on discontinuous density gradients leads to an increase in oxidative DNA damage? SUMMARY ANSWER: The colloidal silicon solutions that are commonly used to prepare human spermatozoa for assisted reproduction technology (ART) purposes contain metals in concentrations that promote free radical-mediated DNA damage. WHAT IS KNOWN ALREADY: Sporadic reports have already appeared indicating that the use of colloidal silicon-based discontinuous density gradients for sperm preparation is occasionally associated with the induction of oxidative DNA damage. The cause of this damage is however unknown. STUDY DESIGN, SIZE, DURATION: This study comprised a series of experiments designed to: (i) confirm the induction of oxidative DNA damage in spermatozoa prepared on commercially available colloidal silicon gradients, (ii) compare the levels of damage observed with alterative sperm preparation techniques including an electrophoretic approach and (iii) determine the cause of the oxidative DNA damage and develop strategies for its prevention. The semen samples employed for this analysis involved a cohort of >50 unselected donors and at least three independent samples were used for each component of the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The setting was a University biomedical science laboratory. The major techniques employed were: (i) flow cytometry to study reactive oxygen species generation, lipid peroxidation and DNA damage, (ii) computer-aided sperm analysis to measure sperm movement and (iii) inductively coupled mass spectrometry to determine the elemental composition of sperm preparation media. MAIN RESULTS AND THE ROLE OF CHANCE: Oxidative DNA damage is induced in spermatozoa prepared on PureSperm((r)) discontinuous colloidal silicon gradients (P < 0.001 versus repeated centrifugation) because this medium contains metals, particularly Fe, Al and Cu, which are known to promote free radical generation in the immediate vicinity of DNA. This damage can be significantly accentuated by reducing agents, such as ascorbate (P < 0.001) and inhibited by selective chelation (P < 0.001). This problem is not confined to PureSperm((r)); analysis of additional commercial sperm preparation media revealed that metal contamination is a relatively constant feature of such products. LIMITATIONS, REASONS FOR CAUTION: While the presence of metals, particularly transition metals, may exacerbate the levels of oxidative DNA damage seen in human spermatozoa, the significance of such damage has not yet been tested in suitably powered clinical trials. WIDER IMPLICATIONS OF THE FINDINGS: The results explain why the preparation of spermatozoa on discontinuous colloidal silicon gradients can result in oxidative DNA damage. The results are of immediate relevance to the development of safe, effective protocols for the preparation of spermatozoa for ART purposes. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Australian Health and Medical Research Council. One of the authors (R.J.A.) has had a consultantship with a biotechnology company, NuSep, interested in the development of electrophoretic methods of sperm preparation. He has no current financial interest in this area. None of the other authors have a conflict of interest to declare. PMID- 25141858 TI - Establishment of a reborn MMV-microarray technology: realization of microbiome analysis and other hitherto inaccessible technologies. AB - BACKGROUND: With the accelerating development of bioscience, the problem of research cost has become important. We previously devised and developed a novel concept microarray with manageable volumes (MMV) using a soft gel. It demonstrated the great potential of the MMV technology with the examples of 1024 parallel-cell culture and PCR experiments. However, its full potential failed to be expressed, owing to the nature of the material used for the MMV chip. RESULTS: In the present study, by developing plastic-based MMVs and associated technologies, we introduced novel technologies such as C2D2P (in which the cells in each well are converted from DNA to protein in 1024-parallel), NGS-non dependent microbiome analysis, and other powerful applications. CONCLUSIONS: The reborn MMV-microarray technology has proven to be highly efficient and cost effective (with approximately 100-fold cost reduction) and enables us to realize hitherto unattainable technologies. PMID- 25141859 TI - The effects of sonic hedgehog signaling pathway components on non-small-cell lung cancer progression and clinical outcome. AB - BACKGROUND: Researchers in recent studies have reported that the sonic hedgehog (Shh) signaling pathway plays a crucial role during tumorigenesis, angiogenesis and cellular differentiation. We investigated the clinical and pathological significances of the Shh pathway and of its lymphangiogenic components in non small-cell lung cancer (NSCLC), namely, Shh, glioma-associated oncogene homolog zinc finger protein 1 (Gli1), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and vascular endothelial growth factor D (VEGF-D). METHODS: The expression of Shh, Gli1, LYVE-1 and VEGF-D in primary NSCLC tissue from 40 patients was examined using immunohistochemical assays, and relationships between expression and clinicopathological data, such as age, gender, histology, tumor size, nodal stage, visceral pleural invasion, lymphatic thromboembolism, recurrence and overall survival were investigated. RESULTS: Of the 40 specimens examined, 25 (62.5%), 20 (50.0%), 11 (27.5%) and 20 (50.0%) were positive for Shh, Gli1, LYVE-1 or VEGF-D expression, respectively. The expression of Gli1 and LYVE-1 were significantly associated (P = 0.011), and Shh and LYVE-1 expression was related to visceral pleural invasion and lymphatic thromboembolism, respectively (P < 0.05). Shh expression levels compared on survival curves were statistically significant in univariate logrank analysis (P = 0.020). However, other clinicopathological factors did not reveal any statistical significance in univariate and multivariate analyses. CONCLUSIONS: To our knowledge, this the first report of the relationship between components of the Shh signaling pathway and prognosis in NSCLC. The expression of Shh, Gli1 and LYVE-1 was found to be associated with clinicopathological factors and survival. Thus, the overexpression of the Shh signaling pathway could serve as a predictor of malignant behavior, including lymphangiogenesis, in NSCLC. PMID- 25141860 TI - Diffuse ventricular fibrosis measured by T1 mapping on cardiac MRI predicts success of catheter ablation for atrial fibrillation. AB - BACKGROUND: There is a complex interplay between the atria and ventricles in atrial fibrillation (AF). Cardiac magnetic resonance (CMR) imaging provides detailed tissue characterization, identifying focal ventricular fibrosis with late gadolinium enhancement (ventricular late gadolinium enhancement) and diffuse fibrosis with postcontrast-enhanced T1 mapping. The aim of the present study was to investigate the relationship between postcontrast ventricular T1 relaxation time on CMR and freedom from AF after pulmonary vein isolation. METHODS AND RESULTS: One hundred three patients undergoing catheter ablation for symptomatic AF (66% paroxysmal AF; age, 58+/-10 years; left atrial area, 27+/-7 cm(2)) underwent preprocedure CMR to determine postcontrast ventricular T1 time. Follow up included clinical review and 7-day Holter monitors at 6 monthly intervals. All patients underwent successful pulmonary vein isolation. At a mean follow-up of 15+/-7 months, the single procedure success was 74%. Postcontrast ventricular T1 time was significantly shorter in patients with recurrent AF (366+/-73 ms) versus patients without AF recurrence (428+/-90 ms; P=0.002). Univariate predictors of AF recurrence included postcontrast ventricular T1 time, AF type (paroxysmal versus persistent), AF duration, and body mass index. After multivariate analysis, ventricular T1 time (P=0.03) and AF duration (P=0.03) were the only independent predictors. Freedom from AF was present in 84% of patients with a postcontrast ventricular T1 time >380 ms versus 56% in patients with a postcontrast ventricular T1 time <380 ms (P=0.002). CONCLUSIONS: A shorter postcontrast ventricular T1 relaxation time on CMR is associated with reduced freedom from AF after catheter ablation. Diffuse ventricular fibrosis as demonstrated by CMR may, in part, explain recurrent AF after AF ablation. PMID- 25141861 TI - Visualization of epicardial cryoablation lesions using endogenous tissue fluorescence. AB - BACKGROUND: Percutaneous cryoballoon ablation is a commonly used procedure to treat atrial fibrillation. One of the major limitations of the procedure is the inability to directly visualize tissue damage and functional gaps between the lesions. We seek to develop an approach that will enable real-time visualization of tissue necrosis during cryo- or radiofrequency ablation procedures. METHODS AND RESULTS: Cryoablation of either blood-perfused or saline-perfused hearts was associated with a marked decrease in nicotinamide adenine dinucleotide (NADH) fluorescence, leading to a 60% to 70% loss of signal intensity at the lesion site. The total lesion area observed on the NADH channel exhibited a strong correlation with the area identified by triphenyl tetrazolium staining (r=0.89, P<0.001). At physiological temperatures, loss of NADH became visually apparent within 26+/-8 s after detachment of the cryoprobe from the epicardial surface and plateaued within minutes after which the boundaries of the lesions remained stable for several hours. The loss of electrical activity within the cryoablation site exhibited a close spatial correlation with the loss of NADH (r=0.84+/-0.06, P<0.001). Cryoablation led to a decrease in diffuse reflectance across the entire visible spectrum, which was in stark contrast to radiofrequency ablation that markedly increased the intensity of reflected light at the lesion sites. CONCLUSIONS: We confirmed the feasibility of using endogenous NADH fluorescence for the real-time visualization of cryoablation lesions in blood-perfused cardiac muscle preparations and revealed similarities and differences between imaging cryo- and radiofrequency ablation lesions when using ultraviolet and visible light illumination. PMID- 25141862 TI - Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo. AB - Histone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 and H3K4 methylation from a proximal as well as a more distal site, but only if in a correct orientation. This plasticity indicates that the exact location of the attachment site, the native ubiquitin-lysine linkage and ubiquitination cycles are not critical for trans-histone crosstalk in vivo. The flexibility in crosstalk also indicates that other ubiquitination events may promote H3 methylation. PMID- 25141863 TI - Cooperative actions of p21WAF1 and p53 induce Slug protein degradation and suppress cell invasion. AB - How the p53 transcription factor/tumor suppressor inhibits cell invasion is poorly understood. We demonstrate that this function of p53 requires its direct interaction with p21(WAF1), a transcriptional target of p53, and that both p21 and p53 bind to Slug, which promotes cell invasion. Functional studies reveal that p21 and p53 cooperate to facilitate Mdm2-dependent Slug degradation and that this p53 function is mimicked by p53(R273H), a mutant lacking trans-activating activity. These actions of p21 and p53 are induced by gamma-irradiation of cells and also operate in vivo. This is the first study to elucidate a mechanism involving p53 and p21 cooperation. PMID- 25141864 TI - Chitosan microparticles loaded with yeast-derived PCV2 virus-like particles elicit antigen-specific cellular immune response in mice after oral administration. AB - BACKGROUND: Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to improved management and husbandry practices, the availability of several anti-PCV2 vaccines provides an efficient immunological option for reducing the impact of these diseases. Most anti-PCV2 vaccines are marketed as injectable formulations. Although these are effective, there are problems associated with the use of injectable products, including laborious and time-consuming procedures, the induction of inflammatory responses at the injection site, and treatment-associated stress to the animals. Oral vaccines represent an improvement in antigen delivery technology; they overcome the problems associated with injection management and facilitate antigen boosting when an animals' immunity falls outside the protective window. METHODS: Chitosan microparticles were used as both a vehicle and mucosal adjuvant to deliver yeast-derived PCV2 virus-like particles (VLPs) in an attempt to develop an oral vaccine. The physical characteristics of the microparticles, including size, Zeta potential, and polydispersity, were examined along with the potential to induce PCV2-specific cellular immune responses in mice after oral delivery. RESULTS: Feeding mice with PCV2 VLP-loaded, positively-charged chitosan microparticles with an average size of 2.5 MUm induced the proliferation of PCV2 specific splenic CD4+/CD8+ lymphocytes and the subsequent production of IFN-gamma to levels comparable with those induced by an injectable commercial formulation. CONCLUSION: Chitosan microparticles appear to be a safe, simple system on which to base PCV2 oral vaccines. Oral chitosan-mediated antigen delivery is a novel strategy that efficiently induces anti-PCV2 cellular responses in a mouse model. Further studies in swine are warranted. PMID- 25141865 TI - Brightfield proximity ligation assay reveals both canonical and mixed transforming growth factor-beta/bone morphogenetic protein Smad signaling complexes in tissue sections. AB - Transforming growth factor-beta (TGF-beta) is an important regulator of cellular homeostasis and disease pathogenesis. Canonical TGF-beta signaling occurs through Smad2/3-Smad4 complexes; however, recent in vitro studies suggest that elevated levels of TGF-beta may activate a novel mixed Smad complex (Smad2/3-Smad1/5/9), which is required for some of the pro-oncogenic activities of TGF-beta. To determine if mixed Smad complexes are evident in vivo, we developed antibodies that can be used with a proximity ligation assay to detect either canonical or mixed Smad complexes in formalin-fixed paraffin-embedded sections. We demonstrate high expression of mixed Smad complexes in the tissues from mice genetically engineered to express high levels of TGF-beta1. Mixed Smad complexes were also prominent in 15-16 day gestation mouse embryos and in breast cancer xenografts, suggesting important roles in embryonic development and tumorigenesis. In contrast, mixed Smad complexes were expressed at extremely low levels in normal adult mouse tissue, where canonical complexes were correspondingly higher. We show that this methodology can be used in archival patient samples and tissue microarrays, and we have developed an algorithm to quantitate the brightfield read-out. These methods will allow quantitative analysis of cell type-specific Smad signaling pathways in physiological and pathological processes. PMID- 25141866 TI - New aspects of progesterone interactions with the actin cytoskeleton and neurosteroidogenesis in the cerebellum and the neuronal growth cone. AB - The impact of progesterone on neuronal tissues in the central (CNS) and peripheral (PNS) nervous system is of significant scientific and therapeutic interest. Glial and neuronal cells of vertebrates express steroidogenic enzymes, and are able to synthesize progesterone de novo from cholesterol. Progesterone is described to have neuroprotective, neuroreparative, anti-degenerative, and anti apoptotic effects in the CNS and the PNS. Thus, the first clinical studies promise new therapeutic options using progesterone in the treatment of patients with traumatic brain injury. Additionally, experimental data from different animal models suggest further positive effects of progesterone on neurological diseases such as cerebral ischemia, peripheral nerve injury and amyothropic lateral sclerosis. In regard to this future clinical use of progesterone, we discuss in this review the underlying physiological principles of progesterone effects in neuronal tissues. Mechanisms leading to morphological reorganizations of neurons in the CNS and PNS affected by progesterone are addressed, with special focus on the actin cytoskeleton. Furthermore, new aspects of a progesterone-dependent regulation of neurosteroidogenesis mediated by the recently described progesterone binding protein PGRMC1 in the nervous system are discussed. PMID- 25141869 TI - The impact of gestational diabetes and maternal obesity on the mother and her offspring. AB - The in utero maternal metabolic environment is important relative to both short and long term development of the offspring. Although poor fetal growth remains a significant factor relative to long-term outcome, fetal overgrowth is assuming greater importance because of the increase in obesity in the world's populations. Maternal obesity and gestational diabetes are the most common metabolic complications of pregnancy related to fetal overgrowth and more specifically adiposity. Women with gestational diabetes have increased insulin resistance and inadequate insulin response compared with weight-matched controls. Gestational diabetes increases the risk of maternal hypertensive disease (preeclampsia) as well as cesarean delivery. At birth the neonate has increased adiposity and is at risk for birth injury. Multiple studies have reported that children of women with gestational diabetes have a greater prevalence childhood obesity and glucose intolerance; even at glucose concentrations less than currently used to define gestational diabetes, compared with normoglycemic women. Obese women also have increased insulin resistance, insulin response and inflammatory cytokines compared with average weight women both before and during pregnancy. They too are at increased risk for the metabolic syndrome-like disorders during pregnancy that is hypertension, hyperlipidemia, glucose intolerance and coagulation disorders. Analogous to women with gestational diabetes, neonates of obese women are heavier at delivery because of increased fat and not lean body mass. Similarly, these children have an increased risk of childhood adiposity and metabolic dysregulation. Hence, the preconceptional and perinatal period offers a unique opportunity to modify both short and long term risks for both the woman and her offspring. PMID- 25141867 TI - Viral expression and molecular profiling in liver tissue versus microdissected hepatocytes in hepatitis B virus-associated hepatocellular carcinoma. AB - BACKGROUND: The molecular mechanisms whereby hepatitis B virus (HBV) induces hepatocellular carcinoma (HCC) remain elusive. We used genomic and molecular techniques to investigate host-virus interactions by studying multiple areas of the same liver from patients with HCC. METHODS: We compared the gene signature of whole liver tissue (WLT) versus laser capture-microdissected (LCM) hepatocytes along with the intrahepatic expression of HBV. Gene expression profiling was performed on up to 17 WLT specimens obtained at various distances from the tumor center from individual livers of 11 patients with HCC and on selected LCM samples. HBV markers in liver and serum were determined by real-time polymerase chain reaction (PCR) and confocal immunofluorescence. RESULTS: Analysis of 5 areas of the liver showed a sharp change in gene expression between the immediate perilesional area and tumor periphery that correlated with a significant decrease in the intrahepatic expression of HB surface antigen (HBsAg). The tumor was characterized by a large preponderance of down-regulated genes, mostly involved in the metabolism of lipids and fatty acids, glucose, amino acids and drugs, with down-regulation of pathways involved in the activation of PXR/RXR and PPARalpha/RXRalpha nuclear receptors, comprising PGC-1alpha and FOXO1, two key regulators critically involved not only in the metabolic functions of the liver but also in the life cycle of HBV, acting as essential transcription factors for viral gene expression. These findings were confirmed by gene expression of microdissected hepatocytes. Moreover, LCM of malignant hepatocytes also revealed up-regulation of unique genes associated with cancer and signaling pathways, including two novel HCC-associated cancer testis antigen genes, NUF2 and TTK. CONCLUSIONS: Integrated gene expression profiling of whole liver tissue with that of microdissected hepatocytes demonstrated that HBV-associated HCC is characterized by a metabolism switch-off and by a significant reduction in HBsAg. LCM proved to be a critical tool to validate gene signatures associated with HCC and to identify genes that may play a role in hepatocarcinogenesis, opening new perspectives for the discovery of novel diagnostic markers and therapeutic targets. PMID- 25141868 TI - Bacterial and archaeal communities in Lake Nyos (Cameroon, Central Africa). AB - The aim of this study was to assess the microbial diversity associated with Lake Nyos, a lake with an unusual chemistry in Cameroon. Water samples were collected during the dry season on March 2013. Bacterial and archaeal communities were profiled using Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) approach of the 16S rRNA gene. The results indicate a stratification of both communities along the water column. Altogether, the physico-chemical data and microbial sequences suggest a close correspondence of the potential microbial functions to the physico-chemical pattern of the lake. We also obtained evidence of a rich microbial diversity likely to include several novel microorganisms of environmental importance in the large unexplored microbial reservoir of Lake Nyos. PMID- 25141870 TI - The early development of the kidney and implications for future health. PMID- 25141871 TI - Cross-fostering and improved lactation ameliorates deficits in endocrine pancreatic morphology in growth-restricted adult male rat offspring. AB - Uteroplacental insufficiency and poor postnatal nutrition impair adult glucose tolerance and insulin secretion in male rat offspring, which can be partially ameliorated by improving postnatal nutrition. Uteroplacental insufficiency was induced in the WKY rat on day 18 of pregnancy (Restricted) compared to sham operated Controls. Pups were then cross-fostered onto Control or Restricted mothers one day after birth resulting in: (Pup-on-Mother) Control-on-Control, Control-on-Restricted, Restricted-on-Control and Restricted-on-Restricted. Endocrine pancreatic morphology and markers of intrinsic beta-cell function and glucose homeostasis were assessed in male offspring at 6 months. Pancreatic and hepatic gene expression was quantified at postnatal day 7 and 6 months. Restricted pups were born 10-15% lighter than Controls and remained lighter at 6 months. Relative islet and beta-cell mass were 51-65% lower in Restricted-on Restricted compared to Controls at 6 months. Non-fasting plasma C-reactive protein levels were also increased, suggestive of an inflammatory response. Overall, the average number of islets, small islets and proportion of beta-cells per islet correlated positively with birth weight. Intrinsic beta-cell function, estimated by insulin secretion relative to beta-cell mass, was unaffected by Restriction, suggesting that the in vivo functional deficit was attributable to reduced mass, not function. Importantly, these deficits were ameliorated when lactational nutrition was normalized in Restricted-on-Control offspring, who also showed increased pancreatic Igf1r, Pdx1 and Vegf mRNA expression at 7 days compared to Control-on-Control and Restricted-on-Restricted. This highlights lactation as a critical period for intervention following prenatal restraint, whereby deficits in endocrine pancreatic mass and associated impaired in vivo insulin secretion can be ameliorated. PMID- 25141872 TI - Maternal high fat diet during critical windows of development alters adrenal cortical and medullary enzyme expression in adult male rat offspring. AB - We previously reported that a maternal high fat (HF) diet resulted in adult offspring with increased adiposity and hyperleptinemia. As leptin has an inhibitory effect on adrenal steroidogenesis and a stimulatory effect on epinephrine synthesis, we hypothesized that key adrenal steroidogenic and catecholaminergic enzymes would be altered in these offspring. Wistar rats were randomized into three groups at weaning: (1) control dams fed a standard control chow diet from weaning and throughout pregnancy and lactation (CON), (2) dams fed a HF diet from weaning and throughout pregnancy and lactation (MHF) and (3) dams fed standard control chow diet throughout life until conception, then fed a HF diet in pregnancy and lactation (PLHF). Dams were mated at day 100 (P100). After birth at P22 (weaning), male offspring were fed a standard control chow (con) or high fat (hf) diet. At P160, plasma samples and adrenal tissues were collected. Postweaning hf diet significantly elevated plasma corticosterone concentrations in PLHF-hf offspring compared to PLHF-con. MHF nutrition increased adrenal adrenocorticotrophic hormone receptor (ACTH-R) mRNA levels compared to CON-con. 3beta-hydroxysteroid dehydrogenase (3betaHSD) mRNA levels were decreased in MHF compared to PLHF offspring. Phenylethanolamine N-methyltransferase (PNMT) mRNA levels were increased in MHF-hf offspring compared to MHF-con. Plasma homocysteine (HCY) concentrations were significantly elevated in CON-hf and MHF hf offspring compared to chow-fed offspring, associated with elevated intakes of methionine and reduced intakes of pyridoxine. Immunoreactive leptin receptor (ObRb) and PNMT were colocalized in medullary chromaffin cells. This study suggests that a postweaning HF diet in offspring induced changes in adrenal gene expression levels that are dependent upon the level of maternal nutrition. PMID- 25141873 TI - Risk factors for sedentary behavior in young adults: similarities in the inequalities. AB - Physical activity is a known protective factor, with benefits for both metabolic and psychological aspects of health. Our objective was to verify early and late determinants of physical activity in young adults. A total of 2063 individuals from a birth cohort in Ribeirao Preto, Brazil, were studied at the age of 23-25 years. Poisson regression was performed using three models: (1) early model considering birth weight, gestational age, maternal income, schooling and smoking; (2) late model considering individual's gender, schooling, smoking and body mass index; and (3) combined (early + late) model. Physical activity was evaluated using the International Physical Activity Questionnaire, stratifying the individuals into active or sedentary. The general rate of sedentary behavior in the sample was 49.6%. In the early model, low birth weight (relative risk (RR) = 1.186, confidence interval (95%CI) 1.005-1.399) was a risk factor for sedentary activity. Female gender (RR = 1.379, 95%CI = 1.259-1.511) and poor schooling (RR = 1.126, 95%CI = 1.007-1.259) were associated with sedentary behavior in the late model. In the combined model, only female gender and participant's schooling remained significant. An interaction between birth weight and individual's schooling was found, in which sedentary behavior was more prevalent in individuals born with low birth weight only if they had higher educational levels. Variables of early development and social insertion in later life interact to determine an individual's disposition to practice physical activities. This study may support the theoretical model 'Similarities in the inequalities', in which opposed perinatal backgrounds have the same impact over a health outcome in adulthood when facing unequal social achievement during the life-course. PMID- 25141874 TI - Maternal supplementation with vitamin A or beta-carotene and cardiovascular risk factors among pre-adolescent children in rural Nepal. AB - Vitamin A plays an important role in fetal renal and cardiovascular development, yet there has been little research on its effects on cardiovascular risk factors later in childhood. To examine this question, we followed the children of women who had been participants in a cluster-randomized, double blind, placebo controlled trial of weekly supplementation with 7000 MUg retinol equivalents of preformed vitamin A or 42 mg of beta-carotene from 1994 to 1997 in rural Nepal. Women received their assigned supplements before, during and after pregnancy. Over a study period of 3 years, 17,531 infants were born to women enrolled in the trial. In 2006-2008, we revisited and assessed 13,118 children aged 9-13 years to examine the impact of maternal supplementation on early biomarkers of chronic disease. Blood pressure was measured in the entire sample of children. In a subsample of 1390 children, venous blood was collected for plasma glucose, Hb1Ac and lipids and a morning urine specimen was collected to measure the ratio of microalbumin/creatinine. Detailed anthropometry was also conducted in the subsample. The mean +/- s.d. systolic and diastolic blood pressure was 97.2 +/- 8.2 and 64.6 +/- 8.5 mm Hg, respectively, and about 5.0% had high-blood pressure (?120/80 mm Hg). The prevalence of microalbuminuria (?30 mg/g creatinine) was also low at 4.8%. There were no differences in blood pressure or the risk of microalbuminuria between supplement groups. There were also no group differences in fasting glucose, glycated hemoglobin, triglycerides or cholesterol. Maternal supplementation with vitamin A or beta-carotene had no overall impact on cardiovascular risk factors in this population at pre-adolescent age in rural Nepal. PMID- 25141875 TI - Romantic attachment in young adults with very low birth weight - The Helsinki Study of Very Low Birth Weight Adults. AB - Early attachment relationships from infancy onward contribute to attachment patterns later in life, to the ability to build up close relationships and to well-being in general. Severely preterm birth may challenge the development of these attachment relationships. We studied whether there are differences in attachment patterns related to romantic relationships between young adults (mean age 22.4 years, s.d. 2.2 years) with very low birth weight (VLBW, <1500 g; n = 162) and their peers born at term (n = 172), who completed the Experiences in Close Relationships Questionnaire - Revised. Young adults born at VLBW showed lower attachment-related anxiety than their peers born at term (mean difference 9.5%, 95% CI -16.0 to -2.6) when adjusted for sex, age, parental education and being in a romantic relationship currently. The groups did not differ in attachment-related avoidance. In subgroup analyses, the VLBW women born small for gestational age (SGA, birth weight <-2 s.d.) scored on average 14.8% (95% CI 3.1 26.6) higher than the control women on attachment avoidance. The effects remained after the exclusion of 18 participants with neurosensory deficits. We found no evidence for a compromised attachment pattern in young adults born at VLBW, with a possible exception of women born SGA at VLBW. VLBW adults were rather characterized by a lower level of attachment-related anxiety. PMID- 25141876 TI - The utility of focus group interviews to capture dietary consumption data in the distant past: dairy consumption in Kazakhstan villages 50 years ago - ERRATUM. PMID- 25141877 TI - Reducing hospital admissions and improving the diagnosis of COPD in Southampton City: methods and results of a 12-month service improvement project. AB - BACKGROUND: The British Lung Foundation highlighted Southampton City as a hotspot for patients at future risk of chronic obstructive pulmonary disease (COPD) exacerbations due to severe deprivation levels and a high undiagnosed level of disease based on health economic modelling. We developed a strategy spanning primary and secondary care to reduce emergency admissions of patients with acute exacerbations of COPD and increase the diagnosed prevalence of COPD on general practitioner (GP) registers closer to that predicted from local modelling. METHODS: A comprehensive 3-year audit of admissions was performed. Patients who had been admitted with an exacerbation to University Hospital Southampton three or more times in the previous 12 months were cohorted and cared for in a consultant-led, but community based, COPD service. Within primary care, a programme of education and case-based finding was delivered to most practices within the city. RESULTS: Thirty-four patients were found to be responsible for 176 admissions (22% of total COPD admissions) to the hospital. These 34 patients required 185 active interventions during the 12-month period but only 39 hospital admissions. The 30-day readmission rate dropped from 13.4 to 1.9% (P<0.01), confirming the contribution the cohort made to readmissions. Prior to the project, the registered Quality Outcomes Framework prevalence of COPD within the city was 1.5; after just 1 year of the project, the prevalence increased from 1.5 to 2.27%. CONCLUSIONS: The use of medical intelligence to investigate the underlying processes of COPD hospital admissions led to an effective intervention delivered in a consultant-led model. PMID- 25141883 TI - Ebola fever: reconciling planning with risk in U.S. hospitals. PMID- 25141879 TI - Evaluation of neutrophil function during hemodialysis treatment in healthy dogs under anesthesia with sevoflurane. AB - This study evaluated the number and function of neutrophils during 3 hr of hemodialysis in healthy dogs under anesthesia. Isolated neutrophils were used to assess neutrophil adhesion, phagocytosis and the oxidative burst. At 0.5 and 3 hr after the start of hemodialysis treatment, there was a decrease in neutrophil number. The phagocytic ability of neutrophils was decreased 3 hr after the start of hemodialysis. In conclusion, this study demonstrated that hemodialysis reduces the number and phagocytic ability of neutrophils during treatment. However, these changes recover within 24 hr of hemodialysis. PMID- 25141878 TI - Association between physical activity and psychological status among Saudi female students. AB - BACKGROUND: Physical inactivity is common among Saudi females. Many variables are associated with different levels of mental health, including physical activity. This study was designed to determine the correlation between 3 weeks of improved physical activity and psychological factors such as insomnia, depression and attention span. METHODS: Seventy-six female students, of mean age 20.9 +/- 1.4 years, were analyzed. Insomnia, depression and attention were subjectively assessed using the Insomnia Severity Index (ISI), the Beck Depression Inventory (BDI), and the Attention Span Test (AST), respectively. Each subject was given a pedometers and advised to walk at least 6000 steps per day for 3 weeks. Psychological status was assessed before and after the 3 weeks and compared using paired sample t-tests. Pearson correlation was used to determine the association between physical health and psychological factors. RESULTS: Improvements in scores on the ISI (from 7.22 +/- 3.06 to 4.09 +/- 2.80), BDI (from 8.88 +/- 3.13 to 3.98 +/- 2.74) and AST (from 63.86 +/- 3.06 to 77.27 +/- 11.33) were observed after 3 weeks. Physical activity was negatively correlated with ISI (r = -0.74) and BDI (r = -0. 78) and positively correlated with AST (r = 0.69). CONCLUSION: Improved physical activity can be useful in managing insomnia, depression and attention. In female Saudi students, higher levels of physical activity were associated with improved mental health. PMID- 25141884 TI - Role of imaging in the diagnosis of occult hernias. AB - IMPORTANCE: Occult hernias are symptomatic but not palpable on physical examination. This is more commonly seen with inguinal hernias. Early diagnosis and treatment of occult hernias are essential in relieving symptoms and improving patients' quality of life. OBJECTIVE: To determine the effectiveness of imaging ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI)--in the diagnosis of occult inguinal hernia. DESIGN, SETTING, AND PARTICIPANTS: A retrospective medical records review of surgical patients with groin and pelvic pain, 2008-2013, was conducted in a single-surgeon hernia specialty practice. Thirty-six patients met the following inclusion criteria: (1) examination findings suggestive of but not necessarily diagnostic for inguinal hernia; (2) imaging of the groin and/or pelvis with US, CT, and MRI; and (3) an operation to address the groin or pelvic pain. Fifty-nine groins were included. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, and predictive values of US, CT, and MRI for detection of occult inguinal hernia. RESULTS: The number, sensitivity, specificity, positive predictive value, and negative predictive value of each modality were, respectively: US (9, 0.33, 0, 1.00, and 0), CT (39, 0.54, 0.25, 0.86, and 0.06), and MRI (34, 0.91, 0.92, 0.95, and 0.85). Among multiply imaged groins in which CT examination missed a diagnosis of hernia, MRI correctly detected an occult hernia in 10 of 11 cases (91%). CONCLUSIONS AND RELEVANCE: Ultrasonography and CT cannot reliably exclude occult groin abnormalities. Patients with clinical suspicion of inguinal hernia should undergo MRI as the definitive radiologic examination. PMID- 25141885 TI - The impacts of obstructive sleep apnea hypopnea syndrome severity and surgery intervention on psychological and behavioral abnormalities and postoperative recovery in pediatric patients. AB - BACKGROUND: The aim of this study was to investigate the degree of impact of obstructive sleep apnea hypopnea syndrome (OSAHS) severity on pediatric psychological and behavioral abnormalities. MATERIAL AND METHODS: Fifty-one children aged 5-12 years with a confirmed diagnosis of OSAHS were divided into 3 groups according to the severity of OSAHS. They underwent bilateral tonsillectomy plus adenoidectomy or adenoidectomy alone. Repeated polysomnography and integrated visual and auditory continuous performance testing (-IVA-CPT) was performed to assess full-scale response control quotient (FRCQ), full-scale attention quotient (FAQ), and hyperactivity (HYP) before surgery and 3 and 6 months after surgery. RESULTS: Mean FRCQ, FAQ, and HYP significantly improved over time in the 3 groups (FRCQ, F=292.05; FAQ, F=258.27; HYP, F=295.10, all P<0.001). FRCQ and HYP were not significantly different among the groups at the 3 time points. FAQ was significantly different among the groups (F=3.89, P<0.05). For FRCQ, FAQ, and HYP, there was no interaction between time and disease severity. Within groups, the effect of time on the apnea-hypopnea index (AHI) and lowest oxygen saturation (LaSO2) were significant for each group and they were significantly different among the 3 groups at each time point (all P<0.001). CONCLUSIONS: These results suggest that OSAHS may have a significant impact on self-control, attention, and hyperactivity in children, which is gradually alleviated after surgery. Disease severity was not closely related to preoperative mental and psychological function or postoperative recovery. Thus, we find it difficult to determine the impact degree of OSAHS severity on mental and psychological function or predict postoperative recovery by using OSAHS severity alone in children. PMID- 25141886 TI - Suicidal behavior in schizophrenia may be related to low lipid levels. AB - BACKGROUND: Lifetime suicide mortality in people with schizophrenia is approximately 4-5%, which is higher than in the general population. In mood disorders, many studies and meta-analyses have shown a link between suicidal behavior and low lipid levels, especially that of cholesterol, and some studies have also suggested such a relationship in schizophrenia. Therefore, the aim of the present study was to investigate a possible correlation between suicidal behavior and lipid levels in schizophrenia patients recently admitted to a psychiatric hospital. MATERIAL/METHODS: Our study included 148 (69 males, 79 females) schizophrenia patients with a mean age of 32+/-10 years, all recently admitted due to acute exacerbation of their mental illness. Psychometric and laboratory assessments were made within 24-72 hours after hospital admission. The main purpose of the interview was to assess occurrence of any suicidal thoughts, suicidal tendencies, and/or suicide attempts during the 3 months prior to admission. Serum total, LDL and HDL cholesterol, as well as triglycerides and total lipids were measured. RESULTS: A significant association was found between suicidal thoughts and attempts and low total cholesterol, LDL cholesterol, triglycerides, and total lipids, in both male and female patients. In male patients with suicidal tendencies, correlation with low LDL cholesterol and triglycerides did not reach statistical significance. No association with suicidality was found with HDL cholesterol in subjects studied. CONCLUSIONS: The results obtained suggest that, similar to depressed patients, low total and LDL cholesterol, triglycerides, and total lipids can be state-dependent risk factors for suicidal behavior in Polish patients with schizophrenia. PMID- 25141887 TI - An epidemiological analysis of acute flaccid paralysis and its surveillance system in Iraq, 1997-2011. AB - BACKGROUND: Acute flaccid paralysis surveillance (AFP) is an essential strategy of the WHO's Polio Eradication Initiative. This is the first study conducted to estimate the incidence, etiology, distribution, and surveillance performance of AFP in Iraq. METHODS: Surveillance data about the AFP cases under the age of 15 years reported from Iraq during January 1997 to December 2011 were depended in the current study. RESULTS: A total of 4974 cases of AFP were reported from Iraq during the study period, with an annual incidence of 2.5/100,000 population. Guillain-Barre syndrome represented more than half of the reported cases (N = 2611, 52.5%), followed by traumatic neuritis (N = 715, 14.4%), and other CNS infections (N = 292, 5.9%). Poliomyelitis accounted for 166 (3.3%) of cases, the last reported case being in January 2000. Surveillance performance showed that all, but two, indicators were below the required WHO recommended levels. CONCLUSIONS: AFP surveillance remains the gold standard method for poliomyelitis detection. It witnessed dramatic changes over the last two decades. This has raised people's and clinicians' awareness to the importance of promptness in notifying suspected cases and timely transportation of stool specimens to the National Poliovirus Laboratory in Baghdad, or alternatively having more than one laboratory for poliovirus detection in the country, all of which are very useful measures to increase the surveillance performance in the country. PMID- 25141888 TI - Mosquito cell lines: history, isolation, availability and application to assess the threat of arboviral transmission in the United Kingdom. AB - Mosquitoes are highly effective vectors for transmission of human and animal pathogens. Understanding the relationship between pathogen and vector is vital in developing strategies to predict and prevent transmission. Cell lines derived from appropriate mosquito hosts provide a relatively simple tool for investigating the interaction between the host and viruses transmitted by mosquitoes. This review provides a brief overview of the development of mosquito cell lines, methods of isolation, their availability and application for investigating insect-virus interactions. PMID- 25141890 TI - Cytogenetic biomonitoring in mucopolyssacharosis I, II and IV patients treated with enzyme replacement therapy. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate genotoxicity and mutagenicity in peripheral blood and buccal mucosal cells in mucopolysaccharidosis (MPS) I, II or VI patients. METHODS: A total of 12 patients with MPS type I, II and VI attended at the Institute of Genetics and Inborn Errors of Metabolism treated with enzyme replacement therapy (ERT) and 10 healthy control volunteers were included in this study. Mechanically exfoliated cells from cheek mucosa (left and right side) were used to micronucleus test and single cell gel (comet) assay in peripheral blood cells. RESULTS: The results of this study detected the presence of genetic damage in peripheral blood for all individuals with MPS treated with ERT, regardless of type of MPS as depicted by tail moment results. In addition, an increased number of micronucleated cells were found in buccal cells of MPS type II patients. It was also observed an increase of other nuclear alterations closely related to cytotoxicity as depicted by the frequency of pyknosis, karyolysis and karyorrhexis in buccal mucosa cells of MPS VI patients (p < 0.05). CONCLUSION: Taken together, such results demonstrate that metabolic alterations induced by the enzymatic deficiency characteristic of MPS associated with ERT therapy can induce genotoxicity and mutagenicity in peripheral blood and buccal mucosa cells, respectively. This effect appears to be more pronounced to MPS II. PMID- 25141889 TI - Cell replacement therapies: is it time to reprogram? AB - Hematopoietic stem cell transplantations have become a very successful therapeutic approach to treat otherwise life-threatening blood disorders. It is thought that stem cell transplantation may also become a feasible treatment option for many non-blood-related diseases. So far, however, the limited availability of human leukocyte antigen-matched donors has hindered development of some cell replacement therapies. The Nobel-prize rewarded finding that pluripotency can be induced in somatic cells via expression of a few transcription factors has led to a revolution in stem cell biology. The possibility to change the fate of somatic cells by expressing key transcription factors has been used not only to generate pluripotent stem cells, but also for directly converting somatic cells into fully differentiated cells of another lineage or more committed progenitor cells. These approaches offer the prospect of generating cell types with a specific genotype de novo, which would circumvent the problems associated with allogeneic cell transplantations. This technology has generated a plethora of new disease-specific research efforts, from studying disease pathogenesis to therapeutic interventions. Here we will discuss the opportunities in this booming field of cell biology and summarize how the scientists in the Netherlands have joined efforts in one area to exploit the new technology. PMID- 25141891 TI - Antimicrobial activity and agricultural properties of bitter melon (Momordica charantia L.) grown in northern parts of Turkey: a case study for adaptation. AB - This study was designed to determine the adaptation capability of bitter melon (Momordica charantia L.), which is widely grown in tropical and subtropical climates, in northern parts of Turkey. In this study, plant height, number of fruits, fruit length, fruit width, number of seeds and fruit weight of bitter melon grown in field conditions were determined. The antimicrobial effect of the ethanol extract of fruit and seeds against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Salmonella typhi, Aspergillus niger and Candida albicans microorganisms was tested in vitro by the disc diffusion method. In conclusion, plant height (260 cm), number of fruits (16 per plant), number of seeds (30.2 per fruit), fruit width (3.8 cm), fruit length (10.6 cm) and fruit weight (117.28 g fruit(- 1)) were determined; fruits were found to have antimicrobial activity against A. niger; oil and seeds were found to have antimicrobial activity against A. niger and E. coli. PMID- 25141892 TI - UGT1A1*28 polymorphisms: a potential pharmacological biomarker of irinotecan based chemotherapies in colorectal cancer. PMID- 25141893 TI - Resolution of a clinical AmpliChip CYP450 TestTM no call: discovery and characterization of novel CYP2D6*1 haplotypes. AB - A Han Chinese patient failed CYP2D6 genotype analysis with the AmpliChip CYP450 TestTM. The CYP2D6 gene locus of the patient and her son were extensively genotyped including copy number variation and gene resequencing. Two SNPs were discovered on the patient's CYP2D6*1 allele, -498C>A and 1661G>C, while the son's CYP2D6*1 allele had -498C>A only. AmpliChip failure was attributed to the presence of a CYP2D6*1 allele carrying the 1661G>C SNP. Functional analyses of 498C>A did not reveal altered activity in vitro or in vivo suggesting that both novel CYP2D6*1 subvariants are functional. The implementation of pharmacogenetics guided drug therapy relies on accurate clinical-grade genotype analysis. Although the AmpliChip is a reliable platform, numerous allelic (sub)variants and gene arrangements are not detected or may trigger no calls. While such cases may be rare, the clinical/genetic testing community must be aware of the challenges of CYP2D6 testing on the AmpliChip platform and implications regarding accuracy of test results. PMID- 25141894 TI - Development of a broad-based ADME panel for use in pharmacogenomic studies. AB - AIM: To optimally address the interindividual variability observed in pharmacokinetic drug response, we have created a custom genotyping panel that interrogates most of the key genetic variations present in a set of 181 prioritized genes responsible for the absorption, distribution, metabolism and excretion (ADME) of many therapeutic agents. This consensus list of genes and variants was based on the ADME core and extended gene lists compiled by a group of pharmaceutical companies as having relevance. Although these pharmacokinetic genes and pathways are well known, tools that can interrogate a large number of these genes simultaneously within a single experiment are not currently available. METHODS: Using novel design strategies, we have developed an optimized and validated ADME genotyping panel, encompassing approximately 3000 variants, that has broad applicability to any study or clinical trial that would benefit from the evaluation of an extensive list of ADME genes. RESULTS & CONCLUSION: Over the course of three design iterations, overall assay conversion rates were improved from 83 to 97% resulting in a panel that fills in many of the gaps in coverage present on currently available commercial genotyping assays. The utility of the assay has been demonstrated by the screening of more than 1000 samples resulting in the discovery of novel pharmacogenomic associations. The assay, and the underlying methods, will continue to be a valuable tool for use in future pharmacogenomic studies. PMID- 25141895 TI - Analysis of compound heterozygous CYP2C19 genotypes to determine cis and trans configurations. AB - BACKGROUND: Through allele specific PCR we studied 220 CYP2C19 compound heterozygous samples, of unknown ethnicity, to determine the haplotype for each of the variations within a sample. MATERIALS & METHODS: The genotypes assessed were: 180 *2 and *17 samples (100% in trans); 20 *2 and *11 samples (100% in cis); ten *4 and *17 samples (50% of the samples were *1/*4B and 50% *4A/*17); six *2, *11 and *17 samples (100% showed *2 and *11 in cis, and *17 in trans); two *2, *4 and *17 samples (100% *4B with *2 in trans); one sample with *17 and *34 (these were in trans); and one sample that contained *2, *17, c.463G>T (p.E155X; *17 and c.463G>T were in cis, with *2 in trans). RESULTS & CONCLUSION: In our study, we observed a different frequency for the *4B allele (when a sample contains both *4 and *17); and identified *17 occurring in cis with a novel nonsense allele. Accurately assessing a patient's genotype, including assignment of a haplotype, can be important when making a phenotype prediction. PMID- 25141897 TI - Personalized pharmacogenomics profiling using whole-genome sequencing. AB - AIM: Pharmacogenomics holds promise to rationalize drug use by minimizing drug toxicity and at the same time increase drug efficacy. There are currently several assays to screen for known pharmacogenomic biomarkers for the most commonly prescribed drugs. However, these genetic screening assays cannot account for other known or novel pharmacogenomic markers. MATERIALS & METHODS: We analyzed whole-genome sequences of 482 unrelated individuals of various ethnic backgrounds to obtain their personalized pharmacogenomics profiles. RESULTS: Bioinformatics analysis revealed 408,964 variants in 231 pharmacogenes, from which 26,807 were residing on exons and proximal regulatory sequences, whereas 16,487 were novel. In silico analyses indicated that 1012 novel pharmacogene-related variants possibly abolish protein function. We have also performed whole-genome sequencing analysis in a seven-member family of Greek origin in an effort to explain the variable response rate to acenocoumarol treatment in two family members. CONCLUSION: Overall, our data demonstrate that whole-genome sequencing, unlike conventional genetic screening methods, is necessary to determine an individual's pharmacogenomics profile in a more comprehensive manner, which, combined with the gradually decreasing whole-genome sequencing costs, would expedite bringing personalized medicine closer to reality. PMID- 25141896 TI - Influence of donor-recipient CYP3A4/5 genotypes, age and fluconazole on tacrolimus pharmacokinetics in pediatric liver transplantation: a population approach. AB - AIM: To characterize the effect of donor and recipient CYP3A4, CYP3A5 and ABCB1 genotypes as well as relevant patient characteristics on tacrolimus pharmacokinetics in pediatric liver transplantation. PATIENTS & METHODS: Data from 114 pediatric liver transplant recipients were retrospectively collected during the first 3 months following transplantation. Population pharmacokinetic analysis was performed using nonlinear mixed effects modeling, including characterization of influential covariates. RESULTS: A two-compartment model with first order elimination best fitted the data. Estimates of apparent volume of the central compartment, intestinal clearance, hepatic clearance and intercompartmental clearance were 79 l, 0.01 l/h, 10.9 l/h and 105 l/h, respectively. Time post-transplantation, recipient age, donor CYP3A5 and CYP3A4 genotypes and fluconazole administration significantly influenced tacrolimus apparent clearance while bodyweight influenced volume of distribution. CONCLUSION: The proposed model displayed acceptable fitting performances and enabled identification of statistically significant and clinically relevant covariates on tacrolimus pharmacokinetics in the early pediatric post liver transplantation period. PMID- 25141898 TI - Pharmacogenetic research in partnership with American Indian and Alaska Native communities. AB - Pharmacogenetics is a subset of personalized medicine that applies knowledge about genetic variation in gene-drug pairs to help guide optimal dosing. There is a lack of data, however, about pharmacogenetic variation in underserved populations. One strategy for increasing participation of underserved populations in pharmacogenetic research is to include communities in the research process. We have established academic-community partnerships with American Indian and Alaska Native people living in Alaska and Montana to study pharmacogenetics. Key features of the partnership include community oversight of the project, research objectives that address community health priorities, and bidirectional learning that builds capacity in both the community and the research team. Engaging the community as coresearchers can help build trust to advance pharmacogenetic research objectives. PMID- 25141899 TI - Calcineurin inhibitors and hypertension: a role for pharmacogenetics? AB - Hypertension is a common side effect of calcineurin inhibitors (CNIs), which are drugs used to prevent rejection after transplantation. Hypertension after kidney transplantation has been associated with earlier graft failure and higher cardiovascular mortality in the recipient. Recent data indicate that enzymes and transporters involved in CNI pharmacokinetics and pharmacodynamics, including CYP3A5, ABCB1, WNK4 and SPAK, are also associated with salt-sensitive hypertension. These insights raise the question whether polymorphisms in the genes encoding these proteins increase the risk of CNI-induced hypertension. Predicting who is at risk for CNI-induced hypertension may be useful for when selecting specific interventions, including dietary salt restriction, thiazide diuretics or a CNI-free immunosuppressive regimen. This review aims to explore the pharmacogenetics of CNI-induced hypertension, highlighting the knowns and unknowns. PMID- 25141900 TI - Parkinson's disease pharmacogenomics: new findings and perspectives. AB - Parkinson's disease (PD) is unique among neurodegenerative disorders because a highly effective pharmacological symptomatic treatment is available. The marked variability in drug response and in adverse profiles associated with this treatment led to the search of genetic markers associated with these features. We present a review of the literature on PD pharmacogenetics to provide a critical discussion of the current findings, new approaches, limitations and recommendations for future research. Pharmacogenetics studies in this field have assessed several outcomes and genes, with special focus on dopaminergic genes, mainly DRD2, which is the most important receptor in nigrostriatal pathway. The heterogeneity in methodological strategies employed by different studies is impressive. The question of whether PD pharmacogenetics studies will improve clinical management by causing a shift from a trial-and-error approach to a pharmacological regimen that takes into account the individual variability remains an open question. Collaborative longitudinal studies with larger sample sizes, better outcome definitions and replication studies are required. PMID- 25141901 TI - An iridoid glucoside and the related aglycones from Cornus florida. AB - A new iridoid glucoside, cornusoside A (1), and four new natural product iridoid aglycones, cornolactones A-D (2-5), together with 10 known compounds were isolated from the leaves of Cornus florida. The structures of compounds 1-5 were established by interpretation of their spectroscopic data. Cornolactone B (3) is the first natural cis-fused tricyclic dilactone iridoid containing both a five- and a six-membered lactone ring. A biosynthesis pathway is proposed for cornolactones C (4) and D (5), the C-6 epimers of compounds 1-3. PMID- 25141902 TI - Quality of life measured by OHIP-14 and GOHAI in elderly people from Bialystok, north-east Poland. AB - BACKGROUND: The Oral Health Impact Profile-14 (OHIP-14) and the Geriatric/General Oral Health Assessment Index (GOHAI) have never been compared for a group of the same subjects in the Polish population. The aim of the study was to compare the OHIP-14 and GOHAI measures. METHODS: 178 independently living people over the age of 55 were included in the study. The GOHAI and OHIP-14 measures were used. Other variables included age, gender, self-ratings of oral general health, education, number of missing teeth, chewing problems and dry mouth. RESULTS: The mean age of respondents was 70.8 years. The internal reliability (Cronbach's alpha) showed a high internal consistency for both measures. Spearman's rank correlation coefficient between the GOHAI and OHIP-14 scores was 0.81. Using the additive method of creating scores, 1.1% of respondents had the GOHAI score of zero, indicating no impact from oral conditions, while 13.5% of them had an OHIP-14 score of zero. Dental status, partial dentures, chewing problems, dry mouth and self-rated oral health were significantly associated with the results of the GOHAI and the OHIP-14 (Kruskal-Wallis test, Mann-Whitney U test). The numbers of preserved and missing teeth significantly correlated with the GOHAI and the OHIP 14, while DMF was significantly associated with the GOHAI only. 6 individuals with discrepant results were revealed. After the exclusion of the abovementioned patients, the internal reliability (Cronbach's alpha) still showed a high internal consistency, and the correlation between the GOHAI and OHIP-14 scores using Spearman's rank-correlation coefficient increased to 0.87. This phenomenon was identified as a "fatigue effect". CONCLUSIONS: There was a strong correlation between the GOHAI and the OHIP-14. Both instruments demonstrated good discriminant properties and helped capture the respondents' oral health problems. The questionnaires should be randomly distributed to avoid the influence of "fatigue effect" on the results of a comparison of different measures. PMID- 25141904 TI - Emerging drugs for diabetic macular edema. AB - INTRODUCTION: Diabetic macular edema (DME) is the most common cause of visual impairment due to diabetic retinopathy. The treatment of DME has recently undergone a paradigm shift. Traditionally, photocoagulation was standard treatment, but pharmacologic therapies are becoming increasingly used for this purpose. All currently available drug therapies for DME are either anti-VEGF agents or corticosteroids. AREAS COVERED: The pathogenesis of DME involves angiogenesis, inflammation and oxidative stress. The scientific rationale to treat DME through the pharmacologic blockade of VEGF and other pro-angiogenic factors is discussed. The fluocinolone insert is approved for the treatment of DME in several European countries, but not in the US at this time. Some medications that are already approved for other retinal diseases, most prominently aflibercept and the dexamethasone delivery system, have recently obtained approval for DME in the US. Other compounds are being studied in earlier phase clinical trials. EXPERT OPINION: Pharmacologic treatment of DME will likely become increasingly used, especially for patients with edema involving the fovea. At this time, the two main classes of medication for treatment of DME are anti VEGF agents and corticosteroids. As we continue to collect clinical trials data, the precise role of individual agents, and the continuing role for photocoagulation, will become more clear. PMID- 25141903 TI - Age trend of the male to female sex ratio in surgical gastric cancer patients at a single institution. AB - BACKGROUND: In previous reports concerning the association between sex disparity and age, gastric cancer (GC) patients were simply divided into younger and older groups by age. We analyzed the age trend of the male to female sex ratio (MFSR) in GC based on patient sequential age in order to observe the changing process of MFSR with age. METHODS: One thousand seven hundred fifty-one surgical gastric adenocarcinoma patients aged 26 to 85 years were investigated between January 1996 and December 2010. The patients were grouped by age intervals of 5 years. The Cochran-Armitage trend test was used to determine how the MFSR changed with age. RESULTS: The median age of the 1,751 patients with GC was 60 years (26 to 85 years). There were 1,334 male and 417 female patients (MFSR was 3.20). Cochran Armitage trend test analysis showed that total MFSR increased significantly with age (Z = 5.964, P < 0.0001). Further studies on age groups of 26 to 60 years and 61 to 85 years were conducted. The trend test showed that MFSR increased significantly with age from 26 to 60 years (Z = 7.433, P < 0.0001). However, MFSR did not increase in ages 61 to 85 years (Z = -0.607, P = 0.544). CONCLUSIONS: MFSR in GC presented an increasing trend until 60 years of age. The male GC patients showed an increasing tendency, and female GC patients showed a decreasing tendency with age. This trend reached a plateau phase after 60 years of age. PMID- 25141906 TI - Linear synthesis of the branched pentasaccharide repeats of O-antigens from Shigella flexneri 1a and 1b demonstrating the major steric hindrance associated with type-specific glucosylation. AB - Shigella flexneri serotypes 1b and 1a are Gram-negative enteroinvasive bacteria causing shigellosis in humans. The O-antigen from S. flexneri 1b is a { -> 2) [3Ac/4Ac]-alpha-L-RHAP-(1 -> 2)-alpha-L-Rhap-(1 -> 3)-[2Ac]-alpha-L-Rhap-(1 -> 3) [alpha-D-Glcp-(1 -> 4)]-beta-D-GlcpNAc-(1 -> }n branched polysaccharide ({(Ac)AB(Ac)C(E)D}n). It is identical to that from S. flexneri 1a, except for the 2C-acetate. A concise synthesis of the disaccharide ED, trisaccharides (Ac)C(E)D and C(E)D, tetrasaccharides B(Ac)C(E)D and BC(E)D, and pentasaccharides AB(Ac)C(E)D and ABC(E)D is described starting from a 2-N-acetyl-D-glucosaminide acceptor and using the imidate glycosylation chemistry. The E residue was efficiently introduced via a potent stereoselective [E + D] coupling. In contrast, harsh conditions and appropriate tuning of the donor were required for a high yielding [C + ED] glycosylation. Irrespective of the level of steric bulk at residue C, glycosylation at O-3D of the ED acceptor generated a major change of conformation of the D residue within the obtained C(E)D trisaccharide, as attested by NMR data. Proper manipulation of the constrained C(E)D trisaccharide was necessary to proceed with the stepwise chain elongation at O-3C of an acceptor having the 2C-O-acetyl already in place. The protected intermediates went through a one- to three-step deprotection sequence to give the propyl glycoside targets, as portions of the O-antigens from both S. flexneri 1a and 1b. Protecting group removal was clearly associated with conformational relief, yielding oligosaccharides, for which NMR data were consistent with a (4)C1 conformation for the 3,4-di-O-glycosylated residue D, as in the native bacterial polymers. PMID- 25141907 TI - alpha1-Blockers for the treatment of recurrent urinary tract infections in women with dysfunctional voiding: a prospective randomized study. AB - OBJECTIVES: To evaluate the therapeutic effects of tamsulosin on recurrent urinary tract infections in women with dysfunctional voiding. METHODS: A total of 155 women with recurrent urinary tract infections and dysfunctional voiding were included and randomly assigned to the following groups: uroflowmetry biofeedback (group 1), alpha1-adrenoceptor antagonists (group 2), uroflowmetry biofeedback combined with alpha1-adrenoceptor antagonists (group 3) and no treatment (group 4). Patients were evaluated by the American Urological Association Symptom Index at 3, 6 and 12 months. Urodynamics was carried out in patients of groups 1, 2, and 3 at 3, 6 and 12 months, whereas urodynamics was only carried out at 12 months in group 4. All patients were followed up for 1 year with monthly urine cultures. RESULTS: The incidence of storage and emptying symptoms decreased significantly at 3, 6 and 12 months. Mean flow rate, flow time and voiding volume increased significantly (with a better outcome in patients of group 3), whereas post-void residual urine decreased. Mean opening detrusor pressure and detrusor pressure at maximum flow decreased significantly (with a better outcome in patients of group 3). Mean urethral closure pressure and maximum urethral closure pressure decreased significantly with a more significant decrease for patients in group 3. The prevalence of urinary tract infection decreased significantly in all groups after treatment, and this decrease remained stable during the follow up. CONCLUSIONS: In women with dysfunctional voiding and recurrent urinary tract infection, tamsulosin associated with uroflowmetry biofeedback might be an effective and safe treatment option for improving urinary symptoms and quality of life. PMID- 25141908 TI - A case report of pink breast milk. AB - A woman presented for her postpartum examination alarmed about pink stains on her breast pads and on her infant's burp pads and diapers. The stains were also found in her breast pump and the infant's bottles. Out of concern, she stopped breastfeeding. The diagnosis was colonization of mother and infant with Serratia marcescens. They were managed conservatively without antibiotics. The mother was guided to restart breastfeeding. The infant resumed nursing and continued to thrive. PMID- 25141905 TI - HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia. AB - INTRODUCTION: First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second line ART. METHODS: We investigated patterns and factors associated with multi NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; >= 2 TAMs; or M184V+>= 1 TAM. Virological suppression was defined as viral load (VL) <400 copies/ml at 12 months from switch to second-line. Logistic regression was used to analyze (1) factors associated with multi-NRTI RAMs at first-line failure and (2) factors associated with virological suppression after 12 months on second-line. RESULTS: A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring >= 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with >= 2 TAMs; and 32 with M184V+>= 1 TAM. Factors associated with multi-NRTI RAMs were CD4 <= 200 cells/uL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence >= 95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43-35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. CONCLUSIONS: Multi NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second line therapy. PMID- 25141909 TI - IroT/mavN, a new iron-regulated gene involved in Legionella pneumophila virulence against amoebae and macrophages. AB - Legionella pneumophila is a pathogenic bacterium commonly found in water. Eventually, it could be transmitted to humans via inhalation of contaminated aerosols. Iron is known as a key requirement for the growth of L. pneumophila in the environment and within its hosts. Many studies were performed to understand iron utilization by L. pneumophila but no global approaches were conducted. In this study, transcriptomic analyses were performed, comparing gene expression in L. pneumophila in standard versus iron restricted conditions. Among the regulated genes, a newly described one, lpp_2867, was highly induced in iron-restricted conditions. Mutants lacking this gene in L. pneumophila were not affected in siderophore synthesis or utilization. On the contrary, they were defective for growth on iron-depleted solid media and for ferrous iron uptake. A sequence analysis predicts that Lpp_2867 is a membrane protein, suggesting that it is involved in ferrous iron transport. We thus named it IroT, for iron transporter. Infection assays showed that the mutants are highly impaired in intracellular growth within their environmental host Acanthamoeba castellanii and human macrophages. Taken together, our results show that IroT is involved, directly or indirectly, in ferrous iron transport and is a key virulence factor for L. pneumophila. PMID- 25141910 TI - Anticancer activity and DNA-binding investigations of the Cu(II) and Ni(II) complexes with coumarin derivative. AB - Two new copper(II) (2) and nickel(II) (3) complexes with a new coumarin derivative have been synthesized and structurally characterized. The DNA-binding activities of the two complexes have been investigated by spectrometric titrations, ethidium bromide displacement experiments, CD (circular dichroism) spectral analysis, and viscosity measurements. The results indicate that the two complexes, especially the complex 2, can strongly bind to calf-thymus DNA (CT- DNA). The intrinsic binding constants Kb of the complexes with CT-DNA are 2.99 * 10(5) and 0.61 * 10(5) for 2 and 3, respectively. Comparative cytotoxic activities of the two complexes are also determined by MTT assay. The results show that the drugs designed here have significant cytotoxic activity against the human hepatic (HepG2), human promyelocytic leukemia (HL60), and human prostate (PC3) cell lines. Cell apoptosis was detected by Annexin V/PI flow cytometry, and the results show that the two copper complexes can induce apoptosis of the three human tumor cells. In conclusions, the two complexes show considerable cytotoxic activity against the three human cancer and induce apoptosis of the threes. PMID- 25141912 TI - Designing of peptides with desired half-life in intestine-like environment. AB - BACKGROUND: In past, a number of peptides have been reported to possess highly diverse properties ranging from cell penetrating, tumor homing, anticancer, anti hypertensive, antiviral to antimicrobials. Owing to their excellent specificity, low-toxicity, rich chemical diversity and availability from natural sources, FDA has successfully approved a number of peptide-based drugs and several are in various stages of drug development. Though peptides are proven good drug candidates, their usage is still hindered mainly because of their high susceptibility towards proteases degradation. We have developed an in silico method to predict the half-life of peptides in intestine-like environment and to design better peptides having optimized physicochemical properties and half-life. RESULTS: In this study, we have used 10mer (HL10) and 16mer (HL16) peptides dataset to develop prediction models for peptide half-life in intestine-like environment. First, SVM based models were developed on HL10 dataset which achieved maximum correlation R/R2 of 0.57/0.32, 0.68/0.46, and 0.69/0.47 using amino acid, dipeptide and tripeptide composition, respectively. Secondly, models developed on HL16 dataset showed maximum R/R2 of 0.91/0.82, 0.90/0.39, and 0.90/0.31 using amino acid, dipeptide and tripeptide composition, respectively. Furthermore, models that were developed on selected features, achieved a correlation (R) of 0.70 and 0.98 on HL10 and HL16 dataset, respectively. Preliminary analysis suggests the role of charged residue and amino acid size in peptide half-life/stability. Based on above models, we have developed a web server named HLP (Half Life Prediction), for predicting and designing peptides with desired half-life. The web server provides three facilities; i) half-life prediction, ii) physicochemical properties calculation and iii) designing mutant peptides. CONCLUSION: In summary, this study describes a web server 'HLP' that has been developed for assisting scientific community for predicting intestinal half-life of peptides and to design mutant peptides with better half-life and physicochemical properties. HLP models were trained using a dataset of peptides whose half-lives have been determined experimentally in crude intestinal proteases preparation. Thus, HLP server will help in designing peptides possessing the potential to be administered via oral route (http://www.imtech.res.in/raghava/hlp/). PMID- 25141911 TI - The impact of microRNA-mediated PI3K/AKT signaling on epithelial-mesenchymal transition and cancer stemness in endometrial cancer. AB - Activation of the PI3K/AKT pathway, a common mechanism in all subtypes of endometrial cancers (endometrioid and non-endometrioid tumors), has important roles in contributing to epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) features. MicroRNAs (miRNAs) are small non-coding RNA molecules that concurrently affect multiple target genes, and regulate a wide range of genes involved in modulating EMT and CSC properties. Here we overview the recent advances revealing the impact of miRNAs on EMT and CSC phenotypes in tumors including endometrial cancer via regulating PI3K/AKT pathway. MiRNAs are crucial mediators of EMT and CSC through targeting PTEN-PI3K-AKT-mTOR axis. In endometrial cancer cells, miRNAs can activate or attenuate EMT and CSC by targeting PTEN and other EMT-associated genes, such as Twist1, ZEB1 and BMI-1. More detailed studies of miRNAs will deepen our understanding of the molecular basis underlying PI3K/AKT-induced endometrial cancer initiation and progression. Targeting key signaling components of PI3K/AKT pathway by restoring or inhibiting miRNA function holds promise as a potential therapeutic approach to suppress EMT and CSC in endometrial cancer. PMID- 25141913 TI - Occupations at risk of developing contact allergy to isothiazolinones in Danish contact dermatitis patients: results from a Danish multicentre study (2009-2012). AB - BACKGROUND: In recent years, the prevalence of contact allergy to isothiazolinones has reached epidemic levels. Few studies have presented data on occupations at risk of developing contact allergy to isothiazolinones. OBJECTIVES: To present demographics and examine risk factors for sensitization to methylisothiazolinone (MI), methylchloroisothiazolinone (MCI) in combination with MI and benzisothiazolinone (BIT) in Danish dermatitis patients. MATERIALS AND METHODS: A retrospective epidemiological analysis of data from three Danish hospitals departments was conducted. All patients consecutively patch tested with MI, MCI/MI and BIT between 2009 and 2013 were included. RESULTS: MI contact allergy showed a significantly increased trend in prevalence from 1.8% in 2009 to 4.2% in 2012 (p < 0.001). Females with facial dermatitis mainly drove the increase in 2012. Adjusted logistic regression analysis showed that MI sensitization was significantly associated with occupational exposures, hand and facial dermatitis, age > 40 years, and the occupational groups of tile setters/terrazzo workers, machine operators, and painters. MCI/MI contact allergy was significantly associated with the following high-risk occupations: painting, welding (blacksmiths), machine operating, and cosmetology. The occupational group of painting was frequent in the group of patients with BIT contact allergy. CONCLUSION: Several high-risk occupations for sensitization to isothiazolinones exist. Regulation on the allowed concentration of isothiazolinones, and especially MI, in both consumer products and industrial products is needed. PMID- 25141914 TI - Interaction of the 5-fluorouracil analog 5-fluoro-2'-deoxyuridine with 'N' and 'B' isoforms of human serum albumin: a spectroscopic and calorimetric study. AB - Drugs and metabolites are transported in the blood by plasma proteins, such as human serum albumin (HSA). The uridine analog 2'dFUrd, which is a cytotoxic prodrug metabolite of capecitabine, has remarkable activity against solid tumors when administered orally. We report the results of an in vitro experimental study on the interactions of 2'-dFUrd with the N-isoform (at pH 7.4) and B-isoform (at pH 9.0) of HSA, investigated using fluorescence spectroscopy, circular dichroism (CD), isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and molecular docking. The binding constant (Kb) was higher for the N isoform than for the B-isoform. Thermodynamic parameters, such as enthalpy change (DeltaH degrees ), entropy change (DeltaS degrees ), and Gibbs free energy change (DeltaG degrees ), were also calculated for both isoform interactions using calorimetric techniques. The thermostabilities of HSA and the HSA-2'dFUrd complex were found to be higher for the N-isoform. The interaction of 2'dFUrd with HSA was also explored in molecular docking studies, which revealed that 2'dFUrd was bound to the Sudlow site I in subdomain IIA through multiple modes of interaction, such as hydrophobic interactions and hydrogen bonding. These results suggest that 2'dFUrd has higher binding affinity for the N-isoform of HSA. PMID- 25141915 TI - Inferior mesenteric vein serves as an alternative guide for transection of the pancreatic body during pancreaticoduodenectomy with concomitant vascular resection: a comparative study evaluating perioperative outcomes. AB - BACKGROUND: Tumors of the pancreatic head often involve the superior mesenteric and portal veins. The purpose of this study was to assess perioperative outcomes after pancreaticoduodenectomy (PD) with concomitant vascular resection using the inferior mesenteric vein (IMV) as a guide for transection of the pancreatic body (Whipple at IMV, WATIMV). METHODS: One hundred thirty-seven patients had segmental vein resection during PD between January 2006 and June 2013. Depending on whether the standard approach of creating a tunnel anterior to the mesenterico portal vein (MPV) axis was achieved for pancreatic transection, patients were subjected to a standard PD with vein resection procedure (s-PD + VR, n = 75) or a modified procedure (m-PD + VR, n = 62). Within the m-PD + VR group, 28 patients underwent the WATIMV procedure, while 34 patients underwent the usual procedure of transection, or 'central pancreatectomy' (c-PD + VR). RESULTS: The volume of intraoperative blood loss and the blood transfusion requirements were significantly greater, and the venous wall invasion and neural invasion frequency were significantly higher in the m-PD + VR group compared with the s-PD + VR group. There were no significant differences in the length of hospitalization, postoperative morbidity, and grades of complications between the two groups. Multivariate logistic regression identified intraoperative blood transfusion (P = 0.004) and vascular invasion (P = 0.008) as the predictors of postoperative morbidity. Further stratification of the entire cohort of 62 (45%) patients who underwent m-PD + VR showed a higher rate of negative resection margins (96.4%) in the WATIMV group compared with the c-PD + VR group (76.5%) (P = 0.06). The volume of intraoperative blood loss (P = 0.013), and intraoperative blood transfusion requirements (P = 0.07) were significantly greater in the c-PD + VR group compared with the WATIMV group. Furthermore, high intraoperative blood loss and tumor stage were predictive of a positive resection margin. CONCLUSIONS: 'Whipple at the IMV (WATIMV)' has comparable postoperative morbidity with standard PD + VR. If IMV runs into the splenic vein, it could serve as an alternative guide for transection of the pancreatic body during PD + VR. PMID- 25141916 TI - Confocal microscopy as a useful approach to describe gill rakers of Asian species of carp and native filter-feeding fishes of the upper Mississippi River system. AB - To better understand potential diet overlap among exotic Asian species of carp and native species of filter-feeding fishes of the upper Mississippi River system, microscopy was used to document morphological differences in the gill rakers. Analysing samples first with light microscopy and subsequently with confocal microscopy, the three-dimensional structure of gill rakers in Hypophthalmichthys molitrix, Hypophthalmichthys nobilis and Dorosoma cepedianum was more thoroughly described and illustrated than previous work with traditional microscopy techniques. The three-dimensional structure of gill rakers in Ictiobus cyprinellus was described and illustrated for the first time. PMID- 25141918 TI - Electrical mobilities of multiply charged ionic-liquid nanodrops in air and carbon dioxide over a wide temperature range: influence of ion-induced dipole interactions. AB - The electrical mobilities of hundreds of mass-selected, multiply charged nanodrops (2-6 nm in diameter) of the ionic liquid EMI-BF4 have been measured in air and CO2 at temperatures, T, ranging from 20 to 100 degrees C, extending previous studies, based on EMI-N(CN)2 nanodrops in air at 20 degrees C, to other temperatures and drift gases. The known compressibility of EMI-BF4 removes prior slight ambiguities in the mass-based determination of nanodrop diameters. We confirm the previous finding that the collision cross-sections Omega of these nanodrops, inferred from their electrical mobilities, are related to their diameters d via a relation of the form Omega ~ xipi/4(d + d(g))(2) (1 + betaepsilon*) (1 + f(Kn))(-1), where epsilon* is the ratio between the polarization and thermal energies of the ion-gas molecule system at contact, f(Kn) is a continuum-correction that vanishes in the free-molecule limit, and the coefficients dg, beta, and xi are inferred experimentally as functions of temperature and drift gas. This expression for Omega(d,z) enables determining true (geometric) cross-sections of globular ions from their measured electrical mobilities in molecular gases. We also corroborate prior reports that the drag enhancement factor xi, which remains nearly constant with temperature and drift gas, exceeds slightly the value xim~ 1.36 established by Millikan's oil drop measurements. Unexpectedly, the coefficient beta shows a significant temperature dependence, suggesting that the ion-gas molecule scattering process is affected by T. The effective gas-molecule collision diameter dg is seen to decrease with T, and takes a value in excess of 0.45 nm in CO2 at 20 degrees C, considerably larger than in room-temperature air. PMID- 25141917 TI - Establishing a panel of chemo-resistant mesothelioma models for investigating chemo-resistance and identifying new treatments for mesothelioma. AB - Mesothelioma is inherently chemo-resistant with only 50% of patients responding to the standard of care treatments, and consequently it has a very grim prognosis. The aim of this study was to establish a panel of chemo-resistant mesothelioma models with clinically relevant levels of resistance as tools for investigating chemo-resistance and identifying new treatments for mesothelioma. Chemo-resistant cell lines were established in vitro and characterized in vivo using syngeneic Fischer rats. Tumors derived from all chemo-resistant cell lines were immunohistochemically classified as mesothelioma. Homozygous deletion of p16(INK4A)/p14(ARF) and increased expression of several ATP-binding cassette transporters were demonstrated, consistent with findings in human mesothelioma. Further, the acquisition of chemo-resistance in vitro resulted in changes to tumor morphology and overall survival. In conclusion, these models display many features corresponding with the human disease, and provide the first series of matched parental and chemo-resistant models for in vitro and in vivo mesothelioma studies. PMID- 25141919 TI - A new ArcGIS-based software of uncertainty analysis for nitrate load estimation. PMID- 25141920 TI - Current Resources for Evidence-Based Practice, September/October 2014. PMID- 25141921 TI - Pleiotrophin inhibits melanogenesis via Erk1/2-MITF signaling in normal human melanocytes. AB - Pleiotrophin (PTN) is a secreted heparin-binding protein that is involved in various biological functions of cell growth and differentiation. Little is known about the effects of PTN on the melanocyte function and skin pigmentation. In this study, we investigated whether PTN would affect melanogenesis. PTN was expressed in melanocytes and fibroblasts of human skin. Transfection studies revealed that PTN decreased melanogenesis, probably through MITF degradation via Erk1/2 activation in melanocytes. The inhibitory action of PTN in pigmentation was further confirmed in ex vivo cultured skin and in the melanocytes cocultured with fibroblasts. These findings suggest that PTN is a crucial factor for the regulation of melanogenesis in the skin. PMID- 25141923 TI - HJC, a new arylnaphthalene lignan isolated from Justicia procumbens, causes apoptosis and caspase activation in K562 leukemia cells. AB - The aim of this study is to investigate whether HJC, isolated from Justicia procumbens for the first time, can suppress the proliferation and induce apoptosis of human leukemia K562 cells and finally clarify its related mechanism. The chemical structure of HJC was validated by LC-ESI-MS/MS, cytotoxicity was assayed using MTT, and apoptosis was investigated by flow cytometry. These assays indicated that HJC remarkably inhibited the growth in K562 cells by decreasing cell proliferation, reducing the SOD activity, enhancing ROS levels and inducing apoptosis. Activation of caspase-3 indicated that HJC may be inducing intrinsic and extrinsic apoptosis pathways and that HJC-induced apoptosis was caspase dependent. This study suggests that HJC is a high-potency anti-tumor agent, and it induces apoptosis through a caspase-dependent pathway in human leukemia K562 cells. It also presents a potential alternative to leukemia therapy. PMID- 25141922 TI - Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis. AB - The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain's fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral 'limbic' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal 'associative' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness. PMID- 25141924 TI - In vitro and in vivo effects of xanthorrhizol on human breast cancer MCF-7 cells treated with tamoxifen. AB - This study investigated the herb-drug interaction of xanthorrhizol and tamoxifen in human breast cancer cells. Using MCF-7 cell line as an in vitro model, the herb-drug interaction between xanthorrhizol and tamoxifen was measured by MTT assay, luciferase reporter assay, and cell cycle analysis. The effects of xanthorrhizol on growth/autophagy related signaling were determined by immunostaining, western blotting, and real time RT-PCR. Additionally, the in vivo effect of xanthorrhizol and tamoxifen on athymic nude mice implanted with MCF-7 cells was evaluated. When MCF-7 cells were co-treated with tamoxifen and xanthorrhizol, there were no significant changes in terms of cell number, luciferase activity, percentage S-phase cells and LC3-II expression. However, using the MCF-7 implanted nude mice model, it was possible to detect significantly increased tumor volumes, a larger tumor size, and increased protein expression of P38 and P27(Kip1) in the xanthorrhizol + tamoxifen group compared to the tamoxifen-alone group. It can be concluded that while there is no significant herb-drug interaction between xanthorrhizol and tamoxifen in vitro, there is such an interaction in tumor-bearing mice, which provides important information that affects breast cancer treatment translational research. PMID- 25141925 TI - Glycyrrhetinic acid reverses the lipopolysaccharide-induced hypocontractility to noradrenaline in rat aorta: implications to septic shock. AB - Septic shock and associated vascular hyporeactivity to vasoconstrictor agonists remain a major problem of critical care medicine. Here we report that glycyrrhetinic acid (GA), the active component of licorice, effectively restores vascular contractility in the model of lipopolysaccharide (LPS)-treated rat aorta. GA was as effective as the NO synthase inhibitor N(G)-nitroarginine methylester. GA did not affect the vascular NO levels (measured by EPR spin trapping) and relaxations to L-arginine in LPS-treated rings as well as relaxation to S-nitroso-N-acetylpenicillamine in control rings. Thus, GA may represent an interesting alternative to NO synthase inhibitors in sepsis associated vascular dysfunction. PMID- 25141928 TI - Patient self-testing and self-management of oral anticoagulation with vitamin K antagonists: guidance from the British Committee for Standards in Haematology. PMID- 25141929 TI - The 18th Germinal Centre Meeting. PMID- 25141931 TI - Lessons from evolution: developmental plasticity in vertebrates with complex life cycles. AB - Developmental plasticity is the property of a given genotype to produce different phenotypes in response to the environmental conditions experienced during development. Chordates have two basic modes of development, direct and indirect. Direct development (mode of humans) was derived evolutionarily from indirect development (mode of many amphibians), the major difference being the presence of a larval stage with indirect development; larvae undergo metamorphosis to the juvenile adult. In amphibians, environmental conditions experienced during the larval stage can lead to extreme plasticity in behaviour, morphology and the timing of metamorphosis and can cause variation in adult phenotypic expression (carry-over effects, or developmental programming). Hormones of the neuroendocrine stress axis play pivotal roles in mediating environmental effects on animal development. Stress hormones, produced in response to a deteriorating larval habitat, accelerate amphibian metamorphosis; in mammals, stress hormones hasten the onset of parturition and play an important role in pre-term birth caused by intra-uterine stress. While stress hormones can promote survival in a deteriorating larval or intra-uterine habitat, costs may be incurred, such as reduced growth and size at metamorphosis or birth. Furthermore, exposure to elevated stress hormones during the tadpole or foetal stage can cause permanent neurological changes, leading to altered physiology and behaviour later in life. The actions of stress hormones in animal development are evolutionarily conserved, and therefore amphibians can serve as important model organisms for research on the mechanisms of developmental plasticity. PMID- 25141932 TI - Early infancy - a critical period for development of obesity. AB - Abundant epidemiologic evidence from the developed world now shows that more rapid weight gain during the first half of infancy predicts later obesity and cardio-metabolic risk. In countries in transition, in which stunting is still prevalent, distinguishing the effects of gain in weight from linear growth remains a challenge. Moreover, very few studies to date have incorporated body composition measures during infancy, which is key to understanding determinants of infant weight gain that also predict later obesity. In addition to infant feeding type, potential determinants include the perinatal endocrine milieu. Animal and emerging human data raise the possibility that ensuring adequate leptin exposure to the growing fetus may regulate energy balance as the infant grows. Understanding these pathways, as well as examining the balance between cardiovascular and cognitive effects in both term and preterm infants, will point the way toward effective interventions to alter infant growth to prevent later obesity. PMID- 25141933 TI - Prenatal environmental exposures that may influence beta-cell function or insulin sensitivity in middle age. AB - The associations between fetal environment and diabetes risk are likely mediated by the offspring's diminished pancreatic beta-cell function or reduced insulin sensitivity. Our ability to distinguish between these mechanisms is impeded by the lack of markers describing an individual's gestational environment. Fingerprints, however, are permanently fixed in the first half of gestation, and increased values of a dermatoglyphic marker that contrasts fingerprint ridge counts between the thumbs and fifth fingers (Md15) have been linked to type 2 diabetes. Among 763 adults without known diabetes from the Dutch Hunger Winter Families Study, we tested the associations of Md15 with homeostatic assessment indices of beta-cell function (HOMA-b) and insulin sensitivity (QUICKI). For either outcome index, linear regression models included terms for Md15 tertiles and for maternal history of diabetes as reported by each participant. All models were corrected for sibling pairs and adjusted for age, sex and famine exposures. Increased Md15 was associated with decreased HOMA-b (P = 0.03 for Md15 tertile 3 v. 1) but not with QUICKI. In contrast, maternal history of diabetes was associated with decreased QUICKI (P < 0.001) but not with HOMA-b. Birth weight (available for 520 participants) was positively associated with increased QUICKI (P = 0.04 for birth weight tertile 3 v. 1) but not with HOMA-b. Fingerprint Md15, maternal history of diabetes and birth weight may help to identify specific defects in the control of adult glucose metabolism. Research into the environment associated with Md15 variation may suggest prenatal strategies for optimizing beta-cell function in adult life. PMID- 25141934 TI - The interleukins IL-6 and IL-1Ra: a mediating role in the associations between BMI and birth weight? AB - The biological mechanisms in the association between maternal body mass index (BMI) and birth weight are not well understood, but are likely to involve maternal plasma glucose levels and nutrient transport across the placenta, both important modulators of fetal growth. Adipose tissue contributes to circulating levels of interleukins that may affect glucose metabolism and possibly also placental transport of nutrients. We investigated possible mediating roles of Interleukin 6 (IL-6) and Interleukin 1 Receptor antagonist (IL-1Ra) in 208 pregnant women. Known and hypothesized dependencies between BMI in early pregnancy and fasting glucose, IL-1Ra and IL-6 at gestational weeks 30-32, and birth weight were specified in a path diagram. Standardized regression coefficients, expressing direct, indirect and total effects, were estimated by Bayesian path analysis. Mean (s.d.) BMI was 24.9 kg/m2 (4.2) and mean (s.d.) birth weight 3748 g (454). The total effect of BMI on birth weight was 0.24 (95% credibility interval (CrI) [0.12, 0.36]). The direct effect of IL-1Ra on birth weight was not statistically significant, but significant effects of BMI on IL 1Ra (0.61, 95% CrI [0.51, 0.72]), of IL-1Ra on fasting glucose (0.17, 95% CrI [0.01, 0.34]) and of fasting glucose on birth weight (0.14, 95% CrI [0.01, 0.27]) implied an indirect pathway from BMI via IL-1Ra on birth weight. Approximately 20% of the effect of BMI on birth weight was mediated through IL-1Ra. For IL-6, no such effects were found. Our results indicate that IL-1Ra may be a mediator in the association between BMI and birth weight. PMID- 25141935 TI - Impact of size at birth and prematurity on adult anthropometry in 4744 middle aged Danes - The Inter99 study. AB - Low birth weight is related to increased risk of developing cardiovascular disease and type 2 diabetes in adult life. Since obesity is closely associated with type 2 diabetes and cardiovascular disease, the relationship between size at birth and adult anthropometry is of interest as a mediator of the relationship between birth weight and metabolic diseases. The aim of this study was, therefore, to examine the effect of size at birth and prematurity on measures of adult anthropometry taking adult socio-economic status and lifestyle variables into account. Midwife records with information on mother's age and parity as well as weight, length and maturity at birth were traced in 4744 Danes born between 1939 and 1970. Measures of adult anthropometry (weight, height, body mass index (BMI), waist circumference, hip circumference and waist/hip ratio) had previously been recorded together with information on socio-economic factors, lifestyle and parental diabetes status. Mother's age, parity and diabetes status were associated with offspring birth weight. Size at birth was positively associated with adult height and weight, but only weakly associated with BMI and not associated with waist/hip ratio when adjusted for socio-economic and lifestyle factors. Infants born preterm were less growth restricted at birth and grew to be taller and heavier compared with term infants born small for gestational age. Altogether, this study does not find evidence that obesity or a central fat distribution is mediating the relationship between low birth weight and risk of cardiovascular disease or type 2 diabetes in later life. PMID- 25141936 TI - Relation of maternal hypertension with infant growth in a prospective birth cohort: the ABCD study. AB - The aim of this study was to investigate the assumed positive association of pre existent and pregnancy-induced hypertension with the offspring's weight and length gain in the first 14 months of life. We studied 3994 pregnant women and their offspring in a prospective community-based cohort study, starting between 2003 and 2004 (Amsterdam Born Children and their Development, ABCD study). Questionnaires obtaining information about hypertension during pregnancy were completed, and this was complemented with additional information from the obstetric caregiver. Anthropometry of the offspring was followed during the first 14 months of life. Main outcome measures were presence or absence of growth acceleration in weight or length (normal: DeltaSDS ? 0.67 v. growth acceleration: DeltaSDS > 0.67). The relation between hypertension during pregnancy and weight and length gain was addressed by logistic regression analyses. We found that pre existent hypertension was related to growth acceleration in weight and length. After correction for birth weight and pregnancy duration, the effect remained significant for growth acceleration in weight (OR 1.89; 95% CI 1.21-2.97; P < 0.01). Pregnancy-induced hypertension showed similar results, although correction for birth weight and pregnancy duration rendered the associations non significant. In conclusion, infants of women with pre-existent hypertension during pregnancy more frequently have growth acceleration in weight and length, and yet the mechanisms acting on postnatal growth appear to be different. PMID- 25141937 TI - Inflammation-mediating proteases: structure, function in (patho) physiology and inhibition. AB - Proteases regulating inflammation are versatile enzymes, usually extracellular matrix degrading enzymes that are involved in wound healing, angiogenesis, coagulation, development, apoptosis and other physiological processes. Their dysregulation and increased expression during inflammation can have devastating consequences, promoting etiology of vascular diseases, inflammatory arthritis, cancer, and allograft rejection. In this review several proteases (ADAMTS, granzymes, plasmin, and kallikreins) with different mechanisms and substrates are described in addition to their physiological roles and contribution to inflammation and inflammatory diseases. Inhibition of proteases may therefore represent an attractive strategy for treatment and herein we describe physiological and engineered inhibitors. PMID- 25141938 TI - Roles of secreted phospholipases A2 in the mammalian immune system. AB - Secreted phospholipase A2 (sPLA2) molecules constitute a family of proteins that are involved functionally in many biological processes. In particular, they participate in diverse pathophysiological settings as enzymes that release free fatty acids and lysophospholipids from phospholipids in biological membranes, or as ligands for various cellular receptors. In this review the confirmed or expected functions of sPLA2s in the mammalian immune system are surveyed. Some of the twelve mammalian sPLA2 molecules constitute part of the so-called innate immune system by virtue of their antibacterial, antiviral and antifungal activities. They are also involved in acute inflammation, a protective reaction of the body to infection or injury. The acute inflammation sometimes escapes regulation, becomes chronic and can evolve into a severe pathology. One or more types of sPLA2 are involved in asthma, rheumatoid arthritis, sepsis, atherosclerosis, myocardial infarction, Crohn's disease, ulcerative colitis and cancer. sPLA2s are thus important therapeutic targets as well as biotherapeutic molecules. Improving the selectivity of inhibitors of sPLA2s to be able to target a particular sPLA2 could therefore be one of the most important tasks for future research. PMID- 25141940 TI - Reliability of categorical loudness scaling in the electrical domain: common mistakes. PMID- 25141939 TI - Access to breast reconstruction after mastectomy and patient perspectives on reconstruction decision making. AB - IMPORTANCE: Most women undergoing mastectomy for breast cancer do not undergo breast reconstruction. OBJECTIVE: To examine correlates of breast reconstruction after mastectomy and to determine if a significant unmet need for reconstruction exists. DESIGN, SETTING, AND PARTICIPANTS: We used Surveillance, Epidemiology, and End Results registries from Los Angeles, California, and Detroit, Michigan, for rapid case ascertainment to identify a sample of women aged 20 to 79 years diagnosed as having ductal carcinoma in situ or stages I to III invasive breast cancer. Black and Latina women were oversampled to ensure adequate representation of racial/ethnic minorities. Eligible participants were able to complete a survey in English or Spanish. Of 3252 women sent the initial survey a median of 9 months after diagnosis, 2290 completed it. Those who remained disease free were surveyed 4 years later to determine the frequency of immediate and delayed reconstruction and patient attitudes toward the procedure; 1536 completed the follow-up survey. The 485 who remained disease free at follow-up underwent analysis. EXPOSURES: Disease-free survival of breast cancer. MAIN OUTCOMES AND MEASURES: Breast reconstruction at any time after mastectomy and patient satisfaction with different aspects of the reconstruction decision-making process. RESULTS: Response rates in the initial and follow-up surveys were 73.1% and 67.7%, respectively (overall, 49.4%). Of 485 patients reporting mastectomy at the initial survey and remaining disease free, 24.8% underwent immediate and 16.8% underwent delayed reconstruction (total, 41.6%). Factors significantly associated with not undergoing reconstruction were black race (adjusted odds ratio [AOR], 2.16 [95% CI, 1.11-4.20]; P = .004), lower educational level (AOR, 4.49 [95% CI, 2.31-8.72]; P < .001), increased age (AOR in 10-year increments, 2.53 [95% CI, 1.77-3.61]; P < .001), major comorbidity (AOR, 2.27 [95% CI, 1.01-5.11]; P = .048), and chemotherapy (AOR, 1.82 [95% CI, 0.99-3.31]; P = .05). Only 13.3% of women were dissatisfied with the reconstruction decision-making process, but dissatisfaction was higher among nonwhite patients in the sample (AOR, 2.87 [95% CI, 1.27-6.51]; P = .03). The most common patient-reported reasons for not having reconstruction were the desire to avoid additional surgery (48.5%) and the belief that it was not important (33.8%), but 36.3% expressed fear of implants. Reasons for avoiding reconstruction and systems barriers to care varied by race; barriers were more common among nonwhite participants. Residual demand for reconstruction at 4 years was low, with only 30 of 263 who did not undergo reconstruction still considering the procedure. CONCLUSIONS AND RELEVANCE: Reconstruction rates largely reflect patient demand; most patients are satisfied with the decision making process about reconstruction. Specific approaches are needed to address lingering patient-level and system factors with a negative effect on reconstruction among minority women. PMID- 25141941 TI - Family member involvement in audiology appointments with older people with hearing impairment. AB - OBJECTIVE: This study aimed to investigate family members' involvement in audiology rehabilitation appointments. DESIGN: Audiology appointments were video recorded and analysed using quantitative coding and conversation analysis (CA). STUDY SAMPLE: The study sample included 13 audiologists, 17 older adults with hearing impairment, and 17 family members. RESULTS: Initial coding showed that family members participated in 12% of the total talk time during audiology appointments. The CA results demonstrated that family members were not typically invited to join the conversation. However, family members would self-select to speak by: (1) responding to questions from the audiologist which were directed at the client; (2) self-initiating expansions on clients' turns; and (3) self initiating questions. When family members did participate in the interaction, audiologists typically responded by shifting the conversation back to the client. CONCLUSION: While family members currently have minimal participation in audiology appointments, they display a strong interest in being involved and sharing their experiences of the client's hearing impairment. The findings suggest support for implementing family-centred care principles in audiology practice. PMID- 25141942 TI - Spatio-temporal epidemiology of the cholera outbreak in Papua New Guinea, 2009 2011. AB - BACKGROUND: Cholera continues to be a devastating disease in many developing countries where inadequate safe water supply and poor sanitation facilitate spread. From July 2009 until late 2011 Papua New Guinea experienced the first outbreak of cholera recorded in the country, resulting in >15,500 cases and >500 deaths. METHODS: Using the national cholera database, we analysed the spatio temporal distribution and clustering of the Papua New Guinea cholera outbreak. The Kulldorff space-time permutation scan statistic, contained in the software package SatScan v9.2 was used to describe the first 8 weeks of the outbreak in Morobe Province before cholera cases spread throughout other regions of the country. Data were aggregated at the provincial level to describe the spread of the disease to other affected provinces. RESULTS: Spatio-temporal and cluster analyses revealed that the outbreak was characterized by three distinct phases punctuated by explosive propagation of cases when the outbreak spread to a new region. The lack of road networks across most of Papua New Guinea is likely to have had a major influence on the slow spread of the disease during this outbreak. CONCLUSIONS: Identification of high risk areas and the likely mode of spread can guide government health authorities to formulate public health strategies to mitigate the spread of the disease through education campaigns, vaccination, increased surveillance in targeted areas and interventions to improve water, sanitation and hygiene. PMID- 25141943 TI - The effect of obesity and tobacco smoke exposure on inflammatory mediators and matrix metalloproteinases in rat model. AB - Obesity is characterized by hypertrophy of adipose tissue and chronic obstructive pulmonary disease (COPD) by lung damage; both diseases are associated with systemic low-grade inflammation. There are no animal models combining obesity and COPD; therefore, these diseases were induced simultaneously in rats to analyze their effects on the expression of inflammatory mediators and enzymes involved in lung tissue remodeling. Obesity was induced with sucrose (30%) for 4 months concomitant with tobacco smoke exposure (20 cigarettes/day, 5 days/wk) for the last 2 months. Were evaluated: body weight, abdominal fat, dyslipidemia, glucose tolerance test (GTT), histology, inflammatory mediators with qPCR and enzyme linked immunosorbent assay, matrix metalloproteinases (MMP-2), MMP-9, MMP-12, TIMP-1 and TIMP-2 through qRT-PCR, and MMP-2 and MMP-9 by gelatin zymography. The rats on a sucrose diet exhibited increased body weight, abdominal fat, triglycerides, GTT, and plasma levels of insulin, adiponectin, leptin, resistin, IL-6, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma, upregulated lung IL-6, IL-1beta, TNF-alpha and IFN-gamma, showing hyperplastic bronchial and alveolar epithelium. The animals exposed to sucrose and tobacco smoke exhibited decreased body weight, abdominal fat and plasma levels of leptin, resistin, IL-1beta and IFN-gamma, reducing inflammation but showing emphysematous lesions. Expression of gelatinases and MMP-12 augmented in the rats exposed to tobacco smoke alone or combined with sucrose. Zymography showed prominent gelatinases activity in all the experimental groups. These results suggest that simultaneous exposure to sucrose and tobacco smoke decreases inflammation but results in emphysematous lesions similar to those observed with tobacco smoke exposure, suggesting that obesity does not confer any protective effect against lung damage. PMID- 25141944 TI - Functional vaginal rejuvenation with elastic silicone threads: a 4-year experience with 180 patients. AB - Recently, there has been growing interest in female genital plastic surgery. To the authors' knowledge, no studies have adopted elastic silicone thread for vaginal rejuvenation. This study introduces clinical experience over 4 years with vaginal rejuvenation using elastic silicone thread to specifically assess the overall patient satisfaction (sexual function and correction of the vaginal width). It is hypothesised that this novel surgical method can improve sexual function. Between 2007-2011, 180 patients underwent vaginal rejuvenation using elastic silicone thread performed by the authors at a single institution. Patients with persistent feeling of a wide vagina and/or a decreased ability to reach orgasm were included. Patients were excluded from the study if they were unavailable for follow-up, or if they had been diagnosed with any gynecologic diseases. To measure the 15 degree of improvement with regard to sexual function, this study adopted the validated system; Female Sexual Function Index (FSFI). 92.8% (167/180) of the patients were satisfied with outcome with regard to feelings of correction of vaginal width. Vaginal rejuvenation using elastic silicone thread significantly improved postoperative outcomes, resulting in improved sexual function, with a focus on improving the FSFI score. This is especially prominent in FSFI orgasm subscore. However, a prospective multicentre study would be beneficial to provide patients with the best possible management. PMID- 25141945 TI - Copper-catalyzed decarboxylative C-P cross-coupling of alkynyl acids with H phosphine oxides: a facile and selective synthesis of (E)-1-alkenylphosphine oxides. AB - A novel and efficient copper-catalyzed decarboxylative cross-coupling of alkynyl acids for the stereoselective synthesis of E-alkenylphosphine oxides has been developed. In the presence of 10 mol % of CuCl without added ligand, base, and additive, various alkynyl acids reacted with H-phosphine oxides to afford E alkenylphosphine oxides with operational simplicity, broad substrate scope, and the stereoselectivity for E-isomers. PMID- 25141946 TI - Egyptian herbal tea infusions' antioxidants and their antiproliferative and cytotoxic activities against cancer cells. AB - The antioxidant, antiproliferative and cytotoxic activities against different human cancer cells were investigated in local and recently introduced plants of Mentha sp., Rosmarinus officinalis L. (ROL) and Origanum majorana L. (OML). ROL exhibited the highest antioxidant activities (IC50 8.4 +/- 0.2 MUg/mL) followed by OML and mint species such as Mentha suaveolens 'apple mint' and Mentha longifolia L. exhibiting moderate antioxidant activities. HPLC analysis of leaf extract revealed that rosmarinic acid is the main component followed by caffeic acid. Herbal leaf extracts varied in their proliferation inhibition and cytotoxicity against HeLa, MCF-7 and Jurkat cancer cells in a dose-dependent matter. The highest antiproliferative inhibition and cytotoxic activity were detected in ROL and OML followed by mint. Local herbs might have a potential role as anticancer natural medicines in addition to their high antioxidant activities due to the presence of different phenolics in their aqueous tea extracts. PMID- 25141949 TI - Biotransformation. AB - The field of clinical pharmacology and therapeutics spans a wide spectrum of research areas involving human subjects at both individual and population levels. One of the key concepts relevant to all of these research areas is biotransformation of drug molecules, which can be defined as the chemical modification of drugs within an organism. This issue of the Journal highlights some of the biotransformation pathways and their sources of individual variations. PMID- 25141947 TI - Preventive effect of permethrin-impregnated long-lasting insecticidal nets on the blood feeding of three major pyrethroid-resistant malaria vectors in western Kenya. AB - BACKGROUND: Since the World Health Organization (WHO) adopted the use of long lasting insecticidal nets (LLINs) as a principal strategy for effective malaria prevention and control, pyrethroids have been the only class of insecticides used for LLINs. The dramatic success of insecticide-treated nets (ITNs) and LLINs in African countries, however, has been threatened by the rapid development of pyrethroid resistance in vector mosquitoes. ITNs and LLINs are still used as effective self-protection measures, but there have been few studies on the effectiveness of ITNs and LLINs in areas where vector mosquitoes are pyrethroid resistant. METHODS: To investigate the behavioral pattern of mosquitoes in the houses where LLINs were used, indoor mosquito trappings of Anopheles gambiae s.s., An. arabiensis, and An. funestus s.s. were performed with Centers for Disease Control and Prevention (CDC) miniature light trap equipped with a collection bottle rotator at 2-hour intervals between 4:00 pm and 8:00 am. The trapped female mosquitoes were identified and classified as unfed, blood fed, and gravid. The abdominal contents of fed female mosquitoes were used for DNA extractions to identify the blood source. RESULTS: A large proportion of human blood feeding of An. arabiensis and An. funestus s.s. (but not An. gambiae s.s.) took place during the time people were active outside LLINs. However, during the hours when people were beneath LLINs, these provided protective efficacy as indicated by reduced human blood feeding rates. CONCLUSION: LLINs provided effective protection against pyrethroid-resistant malaria vector populations during bedtime hours. However, protection of LLINs was insufficient during the hours when people were active outside of the bed nets. Such limitation of LLINs will need to be intensively addressed in African countries in the near future. PMID- 25141952 TI - A question-based approach to adopting pharmacogenetics to understand risk for clinical variability in pharmacokinetics in early drug development. AB - Understanding genetic variations that influence pharmacokinetics (PK) in humans is important for optimal clinical use of drugs. Guidances for making decisions on when to conduct pharmacogenetic research during drug development have been proposed by regulatory agencies, but their uniform adoption presents problems due to an inherent lack of flexibility. A questions-based approach (QBA) was developed to enable drug development teams at Merck to iteratively and flexibly evaluate the potential impact of pharmacogenetics (PGx) on clinical pharmacokinetic variability. PMID- 25141953 TI - Genetic markers of cisplatin-induced hearing loss in children. AB - This journal recently published a Commentary by Ratain and colleagues at the University of Chicago that criticizes our work on cisplatin-induced hearing loss in children. It is unfortunate that neither the authors nor the editors of Clinical Pharmacology & Therapeutics corresponded with us to provide an earlier opportunity to address these questions. Here we correct the authors' inaccuracies and provide additional analyses that further strengthen our published findings. PMID- 25141954 TI - ITC commentary on the prediction of digoxin clinical drug-drug interactions from in vitro transporter assays. AB - The "P-glycoprotein" IC50 working group reported an 18- to 796-fold interlaboratory range in digoxin transport IC50 (inhibitor concentration achieving 50% of maximal inhibition), raising concerns about the predictability of clinical transporter-based drug-drug interactions (DDIs) from in vitro data. This Commentary describes complexities of digoxin transport, which involve both uptake and efflux processes. We caution against attributing digoxin transport IC50 specifically to P-glycoprotein (P-gp) or extending this composite uptake/efflux IC50 variability to individual transporters. Clinical digoxin interaction studies should be interpreted as evaluation of digoxin safety, not P gp DDIs. PMID- 25141960 TI - The RNS System: responsive cortical stimulation for the treatment of refractory partial epilepsy. AB - The RNS((r)) System is the first commercially available device to provide closed loop responsive brain stimulation. The system includes a cranially implanted neurostimulator that continually monitors the electrocorticogram through one or two depth and/or subdural cortical strip leads that are placed at the seizure focus. When abnormal electrographic activity is detected, the neurostimulator delivers brief pulses of electrical stimulation to the seizure focus through the implanted leads. In November 2013, the US FDA approved the RNS System as an adjunctive therapy for patients with drug resistant, partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci. Safety and effectiveness of the RNS System for the indicated patient population was demonstrated in a multicenter, randomized, sham-stimulation controlled 2-year pivotal study. An ongoing, prospective, long-term treatment study is currently gathering an additional 7 years of prospective safety and effectiveness data of the RNS System. PMID- 25141959 TI - Genomes in turmoil: quantification of genome dynamics in prokaryote supergenomes. AB - BACKGROUND: Genomes of bacteria and archaea (collectively, prokaryotes) appear to exist in incessant flux, expanding via horizontal gene transfer and gene duplication, and contracting via gene loss. However, the actual rates of genome dynamics and relative contributions of different types of event across the diversity of prokaryotes are largely unknown, as are the sizes of microbial supergenomes, i.e. pools of genes that are accessible to the given microbial species. RESULTS: We performed a comprehensive analysis of the genome dynamics in 35 groups (34 bacterial and one archaeal) of closely related microbial genomes using a phylogenetic birth-and-death maximum likelihood model to quantify the rates of gene family gain and loss, as well as expansion and reduction. The results show that loss of gene families dominates the evolution of prokaryotes, occurring at approximately three times the rate of gain. The rates of gene family expansion and reduction are typically seven and twenty times less than the gain and loss rates, respectively. Thus, the prevailing mode of evolution in bacteria and archaea is genome contraction, which is partially compensated by the gain of new gene families via horizontal gene transfer. However, the rates of gene family gain, loss, expansion and reduction vary within wide ranges, with the most stable genomes showing rates about 25 times lower than the most dynamic genomes. For many groups, the supergenome estimated from the fraction of repetitive gene family gains includes about tenfold more gene families than the typical genome in the group although some groups appear to have vast, 'open' supergenomes. CONCLUSIONS: Reconstruction of evolution for groups of closely related bacteria and archaea reveals an extremely rapid and highly variable flux of genes in evolving microbial genomes, demonstrates that extensive gene loss and horizontal gene transfer leading to innovation are the two dominant evolutionary processes, and yields robust estimates of the supergenome size. PMID- 25141961 TI - Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation. AB - BACKGROUND: Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation. METHODS: This was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio. RESULTS: Serum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p < 0.01). Moreover, FF PlGF correlated positively with number of oocytes retrieved and the ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p < 0.01). CONCLUSIONS: These data provide evidence that FF PlGF correlates with ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This suggests that PlGF may play a role in PCOS pathogenesis and its angiogenic dysregulation. PMID- 25141962 TI - Phototherapy 660 nm for the prevention of radiodermatitis in breast cancer patients receiving radiation therapy: study protocol for a randomized controlled trial. AB - BACKGROUND: Breast neoplasms are the second most common type of cancer worldwide, and radiation therapy is a key component of their treatment. Acute skin reactions are one of the most common side effects of radiation therapy, and prevention of this adverse event has been investigated in several studies. However, a clinically applicable, preventative treatment remains unavailable. It has been demonstrated that application of a low-power laser can promote tissue repair. Therefore, the aim of this trial is to evaluate the effectiveness of an indium gallium aluminum phosphorus (InGaAIP) laser operated at 660 nm in preventing radiodermatitis in women undergoing adjuvant radiotherapy for breast cancer. METHODS/DESIGN: This is a two-arm, randomized controlled trial. A total of 52 patients undergoing radiotherapy for breast cancer (stages I to III) will be enrolled. Patients will be randomly assigned to an intervention group to receive laser therapy (n = 26) or a control group to receive a placebo (n = 26). The laser or placebo will be applied five days a week, immediately before each radiotherapy session. Skin reactions will then be graded weekly by a nurse, a radiotherapist, and an oncologist (all of whom will be blinded) using the Common Toxicity Criteria (CTC) developed by the National Cancer Institute and the Acute Radiation Morbidity Scoring Criteria developed by the Radiation Therapy Oncology Group. Patients will also answer a modified visual analogue scale for pain (a self-evaluation questionnaire). Primary and secondary outcomes will be the prevention of radiodermatitis and pain secondary to radiodermatitis, respectively. DISCUSSION: The ideal tool for preventing radiodermatitis is an agent that mediates DNA repair or promotes cell proliferation. Application of a low-power laser has been shown to promote tissue repair by reducing inflammation and inducing collagen synthesis. Moreover, this treatment approach has not been associated with adverse events and is cost-effective. Thus, the results of this ongoing trial may establish whether use of a low-power laser represents an ideal treatment option for the prevention of radiodermatitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02003599. Registered on 2 December 2013. PMID- 25141963 TI - Current functional metagenomic approaches only expand the existing protease sequence space, but does not presently add any novelty to it. AB - Proteases are a fundamental function in many organisms and thus many ecosystems and yet they are rarely obtained in functional metagenomic screens. Here, we have isolated an active protease gene (M1-2; 613 amino acids) which resided in a 38.4 kb fosmid clone that showed a classical protease-positive phenotype. It was classified as a zinc-dependent metalloprotease, with the closest annotated sequence as a neutral protease from Collimonas fungivorans (62 % similarity and 72 % homology). Further characterisation showed that its optimum temperature and pH were 42 degrees C and 8.0, respectively. Activity was inhibited by EDTA, but inhibition started to be reversed by excess Zn(2+). A putative signal peptide was identified bioinformatically and this may be why this protease was successfully isolated using a functional metagenomic screen. Bioinformatic analysis shows that this does not represent a novel protease, but simply expands the current sequence space of known proteases. PMID- 25141964 TI - PSI showed higher tolerance to Sb(V) than PSII due to stimulation of cyclic electron flow around PSI. AB - The knowledge of the effects of Sb(V) on the physiological characteristics of cyanobacteria was still limited. In the present study, responses of photosystem I and II (PSI and PSII), cyclic electron flow (CEF), and interphotosystem electron transport of Microcystis aeruginosa to 5-100 mg/l Sb(V) were synchronously measured using the Dual-PAM-100. 5 mg/l Sb (V) significantly inhibited PSII activity, but had no significant effects on PSI activity. At higher concentrations of Sb(V), the quantum yield and electron transport of PSI were less affected compared to PSII. The ratio of Y(II)/Y(I) significantly decreased with increasing Sb(V) concentration. It decreased from 0.7 for control to 0.4 for 100 mg/l Sb(V)-treated cells, indicating that the change of the distribution of quantum yields between two photosystems and more serious inhibition of PSII under stress of Sb(V) compared to PSI. CEF was activated associated with the inhibition of linear electron flow after exposure to Sb(V). The contribution of Y(CEF) to the quantum yield and activity of PSI increased with increasing Sb(V) concentrations. The cyclic electron transport rate made a significant contribution to electron transport rate of PSI, especially at high Sb(V) concentration (100 mg/l) and high illumination (above 555 MUmol photons/m(2)/s). The stimulation of CEF was essential for the higher tolerance of PSI than PSII to Sb(V). PMID- 25141965 TI - Early radiotherapy after radical prostatectomy improves cancer-specific survival only in patients with highly aggressive prostate cancer: validation of recently released criteria. AB - OBJECTIVES: To test the effect of radiotherapy administered within 6 months after radical prostatectomy on cancer-specific mortality in prostate cancer patients after stratification according to a risk score. METHODS: Overall, 7616 patients with pT3/4 N0/1 prostate cancer treated with radical prostatectomy between 1995 and 2009 within the Surveillance Epidemiology and End Results Medicare-linked database were included in the study. Competing-risks regression models were carried out to test the effect of early radiotherapy on cancer-specific mortality in the entire cohort, and after stratifying patients according to the risk score based on the number and nature of adverse pathological characteristics (Gleason score 8-10; pT3b/4, lymph node invasion). RESULTS: The risk score was associated with increasing 5- and 10-year cancer-specific mortality rates (P < 0.001). When considering only patients with a risk score >= 2, 5- and 10-year cancer-specific mortality rates were significantly lower for individuals undergoing early radiotherapy compared with their counterparts not receiving early radiotherapy (2.9 and 6.9 vs 5.7 and 16.2%, respectively; P = 0.002). The corresponding number required to treat to prevent one death from prostate cancer at 10-year follow up was 10. Early radiotherapy was not associated with lower cancer-specific mortality rates overall and in patients with a risk score <2. This was confirmed in multivariable analyses, where early radiotherapy decreased the risk of cancer specific mortality only in patients with a risk score >= 2 (P <= 0.02). CONCLUSIONS: The presence of two or more of the following pathological features might be used to identify patients who benefit from early radiotherapy: Gleason score 8-10, pT3b/4 and lymph node invasion. PMID- 25141967 TI - A concise synthesis of (alkynyl)(trifluoromethyl)sulfanes via a bismuth(III) promoted reaction of trimethyl(alkynyl)silane with trifluoromethanesulfanylamide. AB - A bismuth(III)-promoted reaction of trimethyl(alkynyl)silanes with trifluoromethanesulfanylamide is developed, giving rise to (alkynyl)(trifluoromethyl)sulfanes in good yields. PMID- 25141966 TI - Impaired erythrocyte deformability in transgenic HO-1G143H mutant mice. AB - To investigate the potential effects of variation of HO-1 activity on hemorheology, this study compared the hemorheological properties between transgenic HO-1G143H mutant mice and wild-type (WT) control mice. Fresh blood samples were obtained from mice via the ocular venous sinus. The whole blood viscosity was measured using a cone-plate viscometer. Erythrocyte deformability and aggregation was measured using ektacytometry. The elongation index was significantly reduced in the HO-1G143H mutant mice compared to the WT mice at the shear rates of 600, 800, and 1,000 s(-1). The integrated elongation index was decreased in the HO-1G143H mutant mice compared to the WT mice. There was no statistically significant difference between the HO-1G143H mutant mice and the WT mice in terms of whole blood viscosity, aggregation index, amplitude of aggregation, and aggregation half time. The present study demonstrated that a reduction in HO-1 activity results in an impaired erythrocyte deformability. Although the mechanism underlying this effect remains unclear, our study brings to light the participation of HO-1 in the variations of hemorheology. PMID- 25141968 TI - The association between single nucleotide polymorphisms of GSK 3beta gene and sporadic Alzheimer's disease in a cohort of southern Chinese Han population. AB - Recent studies suggest that genetic factors contribute to the pathogenesis of sporadic Alzheimer's disease (sAD). Glycogen synthase kinase-3 beta (GSK 3beta) is an important molecule which regulates tau phosphorylation and neurofibrillary tangles formation. GSK 3beta gene may be a potential candidate gene for the risk of sAD. To investigate the association of the polymorphisms in GSK 3beta gene with sAD, we conducted a case-control study in a southern Chinese Han cohort including 302 sAD patients and 315 control participants. Four single nucleotide polymorphisms (SNPs) (rs3732361, rs56728675, rs60393216, and rs334558) within the promoter region of GSK 3beta gene were selected and genotyped with a polymerase chain reaction-ligase detection (PCR-LDR) method. Logistic regression was used to analyze the association between target SNPs and the risk of sAD. After adjusting for age, sex, and APOE epsilon4 status, no association was revealed between these SNPs and sAD (P > 0.05). The SNPs in the selected regions of GSK 3beta gene are unlikely to confer the susceptibility of sAD in southern Chinese Han population. Further studies with a larger sample size and different ethnic populations are needed to reveal the role of SNPs of GSK 3beta gene in the pathogenesis of sAD. PMID- 25141969 TI - Progenitor genealogy in the developing cerebral cortex. AB - The mammalian cerebral cortex is characterized by a complex histological organization that reflects the spatio-temporal stratifications of related stem and neural progenitor cells, which are responsible for the generation of distinct glial and neuronal subtypes during development. Some work has been done to shed light on the existing filiations between these progenitors as well as their respective contribution to cortical neurogenesis. The aim of the present review is to summarize the current views of progenitor hierarchy and relationship in the developing cortex and to further discuss future research directions that would help us to understand the molecular and cellular regulating mechanisms involved in cerebral corticogenesis. PMID- 25141971 TI - Basal cell adenocarcinoma and Basal cell adenoma of the salivary glands: a clinicopathological review of seventy tumors with comparison of morphologic features and growth control indices. AB - Basal cell adenoma and basal cell adenocarcinoma represent uncommon basaloid salivary gland neoplasms that show marked morphologic similarity. We wished to compare clinical outcome and morphologic features as well as growth and proliferation associated markers for both neoplasms. We reviewed the pathologic features of 70 neoplasms diagnosed as basal cell adenoma or basal cell adenocarcinoma. Observations included maximum mitotic activity and presence or absence of invasion into surrounding normal tissues as well as immunohistochemical studies for Ki-67, caspase 3, p53, and bcl-2. Establishing malignancy on the basis of invasion into surrounding benign tissues, 41 basal cell adenomas and 29 basal cell adenocarcinomas were identified. For tumors with follow-up, recurrence rates were 6.7 % for basal cell adenoma and 16.7 % for basal cell adenocarcinoma. One patient with basal cell adenocarcinoma had distant metastases and died of disease. Overall basal cell adenocarcinomas showed significantly higher values for growth and proliferation markers compared to basal cell adenomas. Salivary gland basal cell adenoma and basal cell adenocarcinoma show morphologic similarity. Basal cell adenocarcinoma can exhibit a locally aggressive behavior and has potential metastatic behavior. The overall mitotic rate and Ki-67 expression were higher in basal cell adenocarcinoma compared to basal cell adenoma, but overlap between the results of these observations in each tumor did not allow for accurate diagnosis or prediction of outcome in individual cases. We conclude that morphologic observation of local tissue invasion is the best marker for separating basal cell adenoma from basal cell adenocarcinoma. PMID- 25141972 TI - Liver cell proliferation and tumor promotion by phenobarbital: relevance for humans? PMID- 25141970 TI - Canalicular adenoma: a clinicopathologic and immunohistochemical analysis of 67 cases with a review of the literature. AB - There is a lack of a comprehensive immunohistochemical (IHC) analysis of canalicular adenoma (CanAd), especially when combined with a description of the unique histologic features. Given the usual small biopsies, IHC may be useful in distinguishing CanAd from other tumors in the differential diagnosis. Retrospective. The patients included 54 females and 13 males (4.2:1), aged 43-90 years, with a mean age at presentation of 69.9 years. Clinical presentation was generally a mass (n = 61) slowly increasing in size (mean 38.5 months), affecting the upper lip (n = 46), buccal mucosa (n = 17) or palate (n = 4), involving the right (n = 29), left (n = 24) or midline (n = 9), without any major salivary gland tumors. The tumors ranged in size from 0.2 to 3 cm (mean 1.2 cm). Most tumors were multilobular or bosselated (76 %), often surrounded by a capsule. Histologically, the tumors were characterized by cystic spaces, tumor cords with beading, tubule formation, and by the presence of luminal squamous balls (n = 41). The cells were cuboidal to columnar with stippled chromatin. Mitoses were inconspicuous. A myxoid stroma (n = 64), sclerosis (n = 42), luminal hemorrhage (n = 51), and luminal microliths (calcifications) (n = 33) were characteristic. Nine (13.4 %) were multifocal. CanAd showed the following characteristic immunohistochemistry findings: CK-pan and S100 protein (strong, diffuse reaction); peripheral or luminal GFAP reaction; CK5/6 and p16 luminal squamous ball reaction; SOX10 nuclear reaction; cytoplasmic p63 reaction. CanAd are unique minor salivary gland tumors showing a distinct architecture and phenotype. They predilect to older women, with the majority multilobulated and affecting the upper lip, multifocal in 13 %; no major salivary gland tumors were identified. S100 protein, CK-pan, GFAP and SOX10 are positive, with luminal squamous balls highlighted by CK5/6 or p16. PMID- 25141973 TI - Effect of a Roux-en-Y gastric bypass on the pharmacokinetics of oral morphine using a population approach. AB - BACKGROUND AND OBJECTIVES: Obesity and opioid use for chronic pain in obese individuals are both important public health concerns. The pharmacokinetics of oral morphine after Roux-en-Y gastric bypass (RYGB) are unknown. Therefore, we aimed to study the pharmacokinetics of oral morphine in morbidly obese patients before and after RYGB surgery, to identify the effects of RYGB and the subsequent reversal of morbid obesity on the pharmacokinetic parameters of morphine. METHODS: The pharmacokinetics of oral morphine (30 mg) were studied in 30 obese patients before (Visit 1) and then 7-15 days (Visit 2) and 6 months (Visit 3) after RYGB. A population pharmacokinetic model was used to describe the time course of the plasma morphine concentration, to study the effect of RYGB on morphine pharmacokinetics and to estimate inter-patient variability. RESULTS: The oral morphine time to maximum plasma concentration (t max) was twofold lower and maximum plasma concentration (C max) was 1.7 times higher at Visit 2, and t max was 7.5 times lower and C max 3.3 times higher at Visit 3 than at Visit 1. The mean oral morphine area under the plasma concentration-time curve (AUC) increased significantly (1.55-fold) between Visits 1 and 3. Changes in body mass index (BMI) after RYGB were clearly associated with decreased apparent oral morphine clearance and apparent central and peripheral morphine volumes of distribution. None of the other anthropometric parameters explained the inter-subject variability in morphine exposure better than BMI. CONCLUSION: RYGB and the BMI reduction that followed it dramatically increased the rate of morphine absorption and slightly increased morphine exposure. The dose of immediate-release forms of morphine may be divided in obese patients after RYGB to prevent adverse events due to early and high morphine plasma peaks. PMID- 25141974 TI - Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers. AB - BACKGROUND: While in vitro and animal studies have shown reduced cytochrome P450 (CYP) 3A activity due to obesity, clinical studies in (morbidly) obese patients are scarce. As CYP3A activity may influence both clearance and oral bioavailability in a distinct manner, in this study the pharmacokinetics of the CYP3A substrate midazolam were evaluated after semi-simultaneous oral and intravenous administration in morbidly obese patients, and compared with healthy volunteers. METHODS: Twenty morbidly obese patients [mean body weight 144 kg (range 112-186 kg) and mean body mass index 47 kg/m(2) (range 40-68 kg/m(2))] participated in the study. All patients received a midazolam 7.5 mg oral and 5 mg intravenous dose (separated by 159 +/- 67 min) and per patient 22 samples over 11 h were collected. Data from 12 healthy volunteers were available for a population pharmacokinetic analysis using NONMEM((r)). RESULTS: In the three-compartment model in which oral absorption was characterized by a transit absorption model, population mean clearance (relative standard error %) was similar [0.36 (4 %) L/min], while oral bioavailability was 60 % (13 %) in morbidly obese patients versus 28 % (7 %) in healthy volunteers (P < 0.001). Central and peripheral volumes of distribution increased substantially with body weight (both P < 0.001) and absorption rate (transit rate constant) was lower in morbidly obese patients [0.057 (5 %) vs. 0.130 (14 %) min(-1), P < 0.001]. CONCLUSIONS: In morbidly obese patients, systemic clearance of midazolam is unchanged, while oral bioavailability is increased. Given the large increase in volumes of distribution, dose adaptations for intravenous midazolam should be considered. Further research should elucidate the exact physiological changes at intestinal and hepatic level contributing to these findings. PMID- 25141976 TI - Proline-rich antimicrobial peptides: potential therapeutics against antibiotic resistant bacteria. AB - The increasing resistance of pathogens to antibiotics causes a huge clinical burden that places great demands on academic researchers and the pharmaceutical industry for resolution. Antimicrobial peptides, part of native host defense, have emerged as novel potential antibiotic alternatives. Among the different classes of antimicrobial peptides, proline-rich antimicrobial peptides, predominantly sourced from insects, have been extensively investigated to study their specific modes of action. In this review, we focus on recent developments in these peptides. They show a variety of modes of actions, including mechanism shift at high concentration, non-lytic mechanisms, as well as possessing different intracellular targets and lipopolysaccharide binding activity. Furthermore, proline-rich antimicrobial peptides display the ability to not only modulate the immune system via cytokine activity or angiogenesis but also possess properties of penetrating cell membranes and crossing the blood brain barrier suggesting a role as potential novel carriers. Ongoing studies of these peptides will likely lead to the development of more potent antimicrobial peptides that may serve as important additions to the armoury of agents against bacterial infection and drug delivery. PMID- 25141977 TI - Temporal transcriptome analysis of the chicken embryo yolk sac. AB - BACKGROUND: The yolk sac (YS) is an extra-embryonic tissue that surrounds the yolk and absorbs, digests and transports nutrients during incubation of the avian embryo as well as during early term mammalian embryonic development. Understanding YS functions and development may enhance the efficient transfer of nutrients and optimize embryo development. To identify temporal large-scale patterns of gene expression and gain insights into processes and mechanisms in the YS, we performed a transcriptome study of the YS of chick embryos on embryonic days (E) E13, E15, E17, E19, and E21 (hatch). RESULTS: 3547 genes exhibited a significantly changed expression across days. Clustering and functional annotation of these genes as well as histological sectioning of the YS revealed that we monitored two cell types: the epithelial cells and the erythropoietic cells of the YS. We observed a significant up-regulation of epithelial genes involved in lipid transport and metabolism between E13 and E19. YS epithelial cells expressed a vast array of lipoprotein receptors and fatty acid transporters. Several lysosomal genes (CTSA, PSAP, NPC2) and apolipoproteins genes (apoA1, A2, B, C3) were among the highest expressed, reflecting the intensive digestion and re-synthesis of lipoproteins in YS epithelial cells. Genes associated with cytoskeletal structure were down-regulated between E17 and E21 supporting histological evidence of a degradation of YS epithelial cells towards hatch. Expression patterns of hemoglobin synthesis genes indicated a high erythropoietic capacity of the YS between E13 and E15, which decreased towards hatch. YS histological sections confirmed these results. We also observed that YS epithelial cells expressed high levels of genes coding for plasma carrier proteins (ALB, AFP, LTF, TTR), normally produced by the liver. CONCLUSIONS: Here we expand current knowledge on developmental, nutritional and molecular processes in the YS. We demonstrate that in the final week of chick embryonic development, the YS plays different roles to support or replace the functions of several organs that have not yet reached their full functional capacity. The YS has a similar functional role as the intestine in digestion and transport of nutrients, the liver in producing plasma carrier proteins and coagulation factors, and the bone marrow in synthesis of blood cells. PMID- 25141978 TI - The potential role of O-GlcNAc modification in cancer epigenetics. AB - There is no doubt that cancer is not only a genetic disease but that it can also occur due to epigenetic abnormalities. Diet and environmental factors can alter the scope of epigenetic regulation. The results of recent studies suggest that O GlcNAcylation, which involves the addition of N-acetylglucosamine on the serine or threonine residues of proteins, may play a key role in the regulation of the epigenome in response to the metabolic status of the cell. Two enzymes are responsible for cyclic O-GlcNAcylation: O-GlcNAc transferase (OGT), which catalyzes the addition of the GlcNAc moiety to target proteins; and O-GlcNAcase (OGA), which removes the sugar moiety from proteins. Aberrant expression of O GlcNAc cycling enzymes, especially OGT, has been found in all studied human cancers. OGT can link the cellular metabolic state and the epigenetic status of cancer cells by interacting with and modifying many epigenetic factors, such as HCF-1, TET, mSin3A, HDAC, and BAP1. A growing body of evidence from animal model systems also suggests an important role for OGT in polycomb-dependent repression of genes activity. Moreover, O-GlcNAcylation may be a part of the histone code: O GlcNAc residues are found on all core histones. PMID- 25141979 TI - The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach. AB - Protein glycation is initiated by a nucleophilic addition reaction between the free amino group from a protein, lipid or nucleic acid and the carbonyl group of a reducing sugar. This reaction forms a reversible Schiff base, which rearranges over a period of days to produce ketoamine or Amadori products. The Amadori products undergo dehydration and rearrangements and develop a cross-link between adjacent proteins, giving rise to protein aggregation or advanced glycation end products (AGEs). A number of studies have shown that glycation induces the formation of the beta-sheet structure in beta-amyloid protein, alpha-synuclein, transthyretin (TTR), copper-zinc superoxide dismutase 1 (Cu, Zn-SOD-1), and prion protein. Aggregation of the beta-sheet structure in each case creates fibrillar structures, respectively causing Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, familial amyloid polyneuropathy, and prion disease. It has been suggested that oligomeric species of glycated alpha synuclein and prion are more toxic than fibrils. This review focuses on the pathway of AGE formation, the synthesis of different types of AGE, and the molecular mechanisms by which glycation causes various types of neurodegenerative disease. It discusses several new therapeutic approaches that have been applied to treat these devastating disorders, including the use of various synthetic and naturally occurring inhibitors. Modulation of the AGE-RAGE axis is now considered promising in the prevention of neurodegenerative diseases. Additionally, the review covers several defense enzymes and proteins in the human body that are important anti-glycating systems acting to prevent the development of neurodegenerative diseases. PMID- 25141980 TI - Burden of stroke in Puerto Rico. AB - Stroke is the fifth leading cause of death and the first cause of long-term disability in Puerto Rico. Trained staff reviewed and independently validated the medical records of patients who had been hospitalized with possible stroke at any of the 20 largest hospitals located in Puerto Rico during 2007, 2009, and 2011. The mean age of the 5005 newly diagnosed stroke patients (51.2% female) was 70 years. At the time of hospitalization, women were 41/2 years older, were less likely to be married (60.2% vs. 39.9%, P < 0.001), smoked less (5.8% vs. 13.4%, P < 0.001), and had significantly higher proportion of diabetes (56.0% vs. 54.8%), hypertension (89.1% vs. 85.0%), and low density lipoprotein-cholesterol (LDL Chol) > 100 mg/dL (65.7% vs. 57.5%) P < 0.05. Ischemic stroke represented 75% of all types of strokes. Atrial fibrillation was mentioned in 7.9% of the medical records. The risk for dying before discharge was similar for both genders, but was 40% higher for women than for men at one-year follow-up: age-adjusted odds ratio = 1.4 (95% confidence interval = 1.2-1.5). PMID- 25141981 TI - Phosphorylation of activating transcription factor-2 (ATF-2) within the activation domain is a key determinant of sensitivity to tamoxifen in breast cancer. AB - Activating transcription factor-2 (ATF-2) has been implicated as a tumour suppressor in breast cancer (BC). c-JUN N-terminal kinase (JNK) and p38 MAPK phosphorylate ATF-2 within the activation domain (AD), which is required for its transcriptional activity. To date, the role of ATF-2 in determining response to endocrine therapy has not been explored. Effects of ATF-2 loss in the oestrogen receptor (ER)-positive luminal BC cell line MCF7 were explored, as well as its role in response to tamoxifen treatment. Genome-wide chromatin binding patterns of ATF-2 when phosphorylated within the AD in MCF-7 cells were determined using ChIP-seq. The expression of ATF-2 and phosphorylated ATF-2 (pATF-2-Thr71) was determined in a series of 1,650 BC patients and correlated with clinico pathological features and clinical outcome. Loss of ATF-2 diminished the growth inhibitory effects of tamoxifen, while tamoxifen treatment induced ATF-2 phosphorylation within the AD, to regulate the expression of a set of 227 genes for proximal phospho-ATF-2 binding, involved in cell development, assembly and survival. Low expression of both ATF-2 and pATF-2-Thr71 was significantly associated with aggressive pathological features. Furthermore, pATF-2 was associated with both p-p38 and pJNK1/2 (< 0.0001). While expression of ATF-2 is not associated with outcome, pATF-2 is associated with longer disease-free (p = 0.002) and BC-specific survival in patients exposed to tamoxifen (p = 0.01). Furthermore, multivariate analysis confirmed pATF-2-Thr71 as an independent prognostic factor. ATF-2 is important for modulating the effect of tamoxifen and phosphorylation of ATF-2 within the AD at Thr71 predicts for improved outcome for ER-positive BC receiving tamoxifen. PMID- 25141982 TI - In vitro culture and characterization of human lung cancer circulating tumor cells isolated by size exclusion from an orthotopic nude-mouse model expressing fluorescent protein. AB - In the present study, we demonstrate an animal model and recently introduced size based exclusion method for circulating tumor cells (CTCs) isolation. The methodology enables subsequent in vitro CTC-culture and characterization. Human lung cancer cell line H460, expressing red fluorescent protein (H460-RFP), was orthotopically implanted in nude mice. CTCs were isolated by a size-based filtration method and successfully cultured in vitro on the separating membrane (MetaCell(r)), analyzed by means of time-lapse imaging. The cultured CTCs were heterogeneous in size and morphology even though they originated from a single tumor. The outer CTC-membranes were blebbing in general. Abnormal mitosis resulting in three daughter cells was frequently observed. The expression of RFP ensured that the CTCs originated from lung tumor. These readily isolatable, identifiable and cultivable CTCs can be used to characterize individual patient cancers and for screening of more effective treatment. PMID- 25141983 TI - Interactions of a low molecular weight inhibitor from Streptomyces sp. MBR04 with human cathepsin D: implications in mechanism of inactivation. AB - Cathepsin D, a lysosomal aspartic protease, is of potential interest as a target for drug design due to its implication in breast and ovarian cancer. The article reports a low molecular weight cathepsin D inhibitor from Streptomyces sp. MBR04. The Mr of the inhibitor was 1,078 Da as determined by MALDI-TOF, and the amino acid analysis showed the presence of Asp, Asp, Gly, Ala, Lys, Leu, Tyr, Trp residues. The steady-state kinetic interactions revealed reversible, competitive, slow-tight-binding nature of the inhibitor with an IC50 and K i values of 3.2 and 2.5 nM, respectively. The binding of the inhibitor with the enzyme and the subsequent conformational changes were monitored by exploiting the intrinsic fluorescence of the surface exposed Trp-54 residue. Based on the fluorescence and circular dichroism studies, we demonstrate that the inhibitor binds to the active site of cathepsin D and causes inactivation. All these kinetic, thermodynamic, and quenching studies suggest that the newly isolated peptidic inhibitor could be a potential scaffold to study and can be used to develop new potent therapeutic lead molecule for the development of drugs. The inhibitor will be significant as a potential lead molecule to target cathepsin D. PMID- 25141984 TI - Construction of an uricase nanoparticles modified au electrode for amperometric determination of uric acid. AB - A method is described for preparation of uricase nanoparticles (100 nm in size) and their direct immobilization onto the Au electrode. The enzyme electrode along with Ag/AgCl as reference and Pt as auxiliary electrode were connected through potentiostat/galvanostat to construct an amperometric uric acid biosensor. The enzyme electrode was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and electrochemical impedance spectroscopy (EIS). The enzyme electrode detected uric acid level as low as 5.0 MUM at a signal-to-noise ratio of 3, within 7 s at pH 8.5 and 40 degrees C. The biosensor showed a linear working range, 0.005 to 0.8 mM for uric acid with a sensitivity of 0.03 mA MUM(-1) cm(-2). The biosensor was evaluated. The biosensor lost only 15 % of its initial activity over a period of 7 months, when stored at 4 degrees C. The fabricated biosensor was successfully employed for determination of uric acid in human serum and urine. PMID- 25141985 TI - The impact of mesenteric tension on pouch outcome and quality of life in patients undergoing restorative proctocolectomy. AB - AIM: The study aimed to establish a method for the measurement of mesenteric tension after ileal pouch-anal anastomosis (IPAA) and to evaluate the impact of tension on clinical outcome and quality of life. METHODS: All consecutive patients undergoing an open IPAA from July 2008 to October 2009 were prospectively enrolled. After the creation of the anastomosis, mesenteric tension was estimated by the surgeon in the operating room on a 10-point scale (1, least tension; 10, most tension). The association was analysed between mesenteric tension defined as low (1-2), medium (3-7) and high (8-10) and postoperative complications and quality of life (Cleveland Clinic Global Scale). RESULTS: A mesenteric tension score was obtained in 134 patients (71 men, 53.0%). Median age was 38.5 (29.3-47.0) years. Fifty-six patients (41.8%) had a low, 59 (44.0%) a medium and 19 (14.2%) a high degree of mesenteric tension. Patients with a high mesenteric tension had a shorter anal transitional zone, a longer distance from the upper border of the symphysis pubis to the apex of the small bowel loop designated for the ileoanal anastomosis, a thinner abdominal wall at the stoma site and a longer distance from the pouch to the ileostomy. The proportion of patients with high mesenteric tension was less after stapled anastomosis. On long term follow-up, patients with high mesenteric tension were more likely to suffer from anastomotic stricture and pouch failure. Pouch function was not influenced by mesenteric tension. CONCLUSION: High mesenteric tension after IPAA is adversely associated with postoperative complications and pouch survival. PMID- 25141986 TI - Occupational contact dermatitis caused by D-limonene. AB - BACKGROUND: Limonene is widely used as a fragrance substance and solvent in cleansing products. Oxidized limonene is a frequent contact allergen among consumers of cosmetics, personal care products, and scented household cleaning products. Less is known about the sources of occupational exposure and occupational contact dermatitis caused by limonene. OBJECTIVE: To report 14 patients with occupational contact allergy to limonene. METHODS: The patients were examined in 2008-2013. An in-house preparation of oxidized limonene was patch tested as 3% and 5% in petrolatum from 2008 to August 2010, and after this as 3%, 1% and 0.3% pet. From 2012 onwards, a commercial test substance of limonene hydroperoxides was also used. We assessed the patients' occupational and domestic exposure to limonene. RESULTS: Occupational limonene allergy was observed in workers who used limonene-containing machine-cleaning detergents and hand cleansers, and in workers who used limonene-containing surface cleaners and dishwashing liquids similar to those used by consumers. In 3 cases, the occupational limonene allergy resulted from work-related use of limonene containing, leave-on cosmetic products. CONCLUSIONS: Limonene is a frequent occupational sensitizer in hand cleansers and cleaning products. Occupational limonene contact allergy may also be caused by exposure to cosmetic products scented with limonene. PMID- 25141987 TI - A metabolic trade-off between phosphate and glucose utilization in Escherichia coli. AB - Getting the most out of available nutrients is a key challenge that all organisms face. Little is known about how they optimize and balance the simultaneous utilization of multiple elemental resources. We investigated the effects of long term phosphate limitation on carbon metabolism of the model organism Escherichia coli using chemostat cultures. We profiled metabolic changes in the growth medium over time and found evidence for an increase in fermentative metabolism despite the aerobic conditions. Using full-genome sequencing and competition experiments, we found that fitness under phosphate-limiting conditions was reproducibly increased by a mutation preventing flux through succinate in the tricarboxylic acid cycle. In contrast, these mutations reduced competitive ability under carbon limitation, and thus reveal a conflicting metabolic benefit in the role of the TCA cycle in environments limited by inorganic phosphate and glucose. PMID- 25141988 TI - Mindful mood balance: a case report of Web-based treatment of residual depressive symptoms. AB - Residual depressive symptoms are associated with increased risk for relapse and impaired functioning. Although there is no definitive treatment for residual depressive symptoms, Mindfulness-Based Cognitive Therapy has been shown to be effective, but access is limited. Mindful Mood Balance (MMB), a Web-based adaptation of Mindfulness-Based Cognitive Therapy, was designed to address this care gap. In this case study, we describe a composite case that is representative of the course of intervention with MMB and its implementation in a large integrated delivery system. Specifically, we describe the content of each of eight weekly sessions, and the self-management skills developed by participating in this program. MMB may be a cost-effective and scalable option in primary care for increasing access to treatments for patients with residual depressive symptoms. PMID- 25141989 TI - Impact of implementing glycated hemoglobin testing for identification of dysglycemia in youth. AB - OBJECTIVES: To determine the impact of the introduction of the glycated hemoglobin (HbA1C) assay for diabetes mellitus diagnosis among children and adolescents aged 6-17 years and to describe the composition of the population of patients with, and at risk for, diabetes using fasting plasma glucose test and HbA1C assay. RESEARCH DESIGN AND METHODS: The Kaiser Permanente Hawaii (KPHI) and Kaiser Permanente Northwest (KPNW) sites identified a 2009 and a 2012 cohort of youth who were aged 6-17 years and continuously enrolled in their cohort year and for 1 year prior. We excluded youth with a type 1 or type 2 diabetes diagnosis before their cohort year. RESULTS: In both sites, fasting plasma glucose testing was significantly more common in 2009 and HbA1C testing was more common in 2012. The proportion with either test increased from 2.56% to 4.02% in KPNW and from 3.18% to 10.48% in KPHI, but the characteristics of the population did not change between 2009 and 2012. In both sites, the characteristics of youth at risk of diabetes changed substantially with a much greater proportion being female (KPNW: 39% vs 55%; KPHI: 35% vs 46%; p < 0.001 for both) and children younger than 10 (KPNW: 7% vs 32%; KPHI: 11% vs 39%; p < 0.001 for both) between 2009 and 2012. The size and composition of the population of youth identified with diabetes was not affected. CONCLUSIONS: Adoption of the HbA1C assay for diabetes diagnosis has increased glycemia testing among youth aged 6-17 years and has altered the composition of the population identified as at risk for diabetes. These findings have important ramifications for targeted screening and diabetes prevention efforts. PMID- 25141991 TI - The influence of visual impairment on pregnancy outcomes. AB - PURPOSE: To investigate whether visually impaired women are at higher risk for adverse maternal and perinatal complications, with an emphasis on visual impairment due to autoimmune etiology. METHODS: A retrospective cohort study compared obstetric, delivery complications and perinatal outcomes of patients with and without a diagnosis of visual impairment in one or both eyes. Multivariable models were conducted to control for confounders. RESULTS: During the study period (1988-2012), 265,741 deliveries were included; of these 80 (0.03%) occurred in visually impaired patients. These patients were significantly older than the comparison group, and had higher rates of gestational diabetes mellitus (GDM) and severe preeclampsia. Visually impaired women had higher rates of delivery prior to 37 weeks gestation and significantly higher rate of delivery by cesarean section (CS). A multivariable analysis model demonstrated that the risk factor for CS and packed cell transfusion in visually impaired women remained significantly high even after controlling for confounders such as maternal age, ethnicity, etc. (weighted OR = 2.04; 95% CI 1.23-3.37; p = 0.006). However, visual impairment was not an independent risk factor for congenital malformations, using another multivariable model (weighted OR = 1.96; 95% CI 0.99 3.85; p = 0.051). Perinatal outcome was comparable between the groups. The sub group of visually impaired women due to possible autoimmune etiology was 19.4% and they had higher rates of recurrent miscarriages and CS compared to the other sub-groups. CONCLUSION: Visually impaired pregnant women are at high risk for CS and packed cell transfusion. Nevertheless, perinatal outcome is comparable to the general population. PMID- 25141990 TI - Carotenoids are effective inhibitors of in vitro hemolysis of human erythrocytes, as determined by a practical and optimized cellular antioxidant assay. AB - beta-Carotene, zeaxanthin, lutein, beta-cryptoxanthin, and lycopene are liposoluble pigments widely distributed in vegetables and fruits and, after ingestion, these compounds are usually detected in human blood plasma. In this study, we evaluated their potential to inhibit hemolysis of human erythrocytes, as mediated by the toxicity of peroxyl radicals (ROO*). Thus, 2,2'-azobis (2 methylpropionamidine) dihydrochloride (AAPH) was used as ROO* generator and the hemolysis assay was carried out in experimental conditions optimized by response surface methodology, and successfully adapted to microplate assay. The optimized conditions were verified at 30 * 10(6) cells/mL, 17 mM of AAPH for 3 h, at which 48 +/- 5% of hemolysis was achieved in freshly isolated erythrocytes. Among the tested carotenoids, lycopene (IC(50) = 0.24 +/- 0.05 MUM) was the most efficient to prevent the hemolysis, followed by beta-carotene (0.32 +/- 0.02 MUM), lutein (0.38 +/- 0.02 MUM), and zeaxanthin (0.43 +/- 0.02 MUM). These carotenoids were at least 5 times more effective than quercetin, trolox, and ascorbic acid (positive controls). beta-Cryptoxanthin did not present any erythroprotective effect, but rather induced a hemolytic effect at the highest tested concentration (3 MUM). These results suggest that selected carotenoids may have potential to act as important erythroprotective agents by preventing ROO*-induced toxicity in human erythrocytes. PMID- 25141992 TI - Effect of CO2 pneumoperitoneum on the proliferation of human ovarian cancer cell line SKOV-3 and the expression of NM23-H1 and MMP-2. AB - OBJECTIVE: This study aims to investigate the impacts of CO2 pneumoperitoneum on the growth of ovarian cancer in nude mice and the expression of tumor metastasis suppressor gene (NM23-H1) and matrix metalloproteinase -2 (MMP-2) in SKOV-3 ovarian cancer cell line cancer tissue. METHOD: Forty five nude mice were used to establish ovarian cancer xenograft models by intraperitoneal injection of human ovarian cancer cell line SKOV-3. Murine xenograft models were divided into four groups: control group (only anesthetized for 0.5 h), laparotomy group (laparotomy for 0.5 h), CO2 pneumoperitoneum of 0.5 h, and CO2 pneumoperitoneum of 1 h group. Mice were killed after 12 weeks to observe intraperitoneal tumor growth and detected mRNA expression of NM23-H1 and MMP-2 in tumor tissues by RT-PCR. RESULT: Our data show that xenograft tumors grew faster in the CO2 pneumoperitoneum groups than that in control and laparotomy groups and even faster in the CO2 pneumoperitoneum of 1 h group. The mRNA expression of NM23-H1 in CO2 pneumoperitoneum groups was significantly lower than that in control group and laparotomy group (P < 0.01). Moreover, the longer duration of CO2 pneumoperitoneum negatively correlated with lower expression of NM23-H1 (P < 0.01). In contrast to NM23-H1, MMP-2 expression was significantly higher in CO2 pneumoperitoneum groups than that in the control group and laparotomy group (P < 0.01) and positively correlated with the duration of CO2 pneumoperitoneum (P < 0.01). In addition, there was a negative correlation between the expression of NM23-H1 and MMP-2 (r = -0.984, P < 0.05). CONCLUSION: The CO2 pneumoperitoneum could promote the proliferation and metastasis of human ovarian cancer in nude mice. This effect was positively correlated with the duration of CO2 pneumoperitoneum. PMID- 25141993 TI - Flower-like dynamics of coupled Skyrmions with dual resonant modes by a single frequency microwave magnetic field. AB - Resonant excitations of confined systems have aroused much attention because of their potential application in future microwave devices and spintronics. Under resonant excitations, the motion of topo-logical objects exhibits circular, elliptical or even stadium-like dynamics. However, more complex non-linear resonant excitations of topological objects in confined systems have seldom been reported and the associated physical mechanism remains unclear. Here, we present an observation of flower-like resonant excitations for coupled skyrmions in Co/Ru/Co nanodisks activated by a single-frequency microwave magnetic field by means of numerical simulation. We find that flower-like dynamics of coupled skyrmions is always accompanied by an excitation of an eigenfrequency near 1.15 GHz, which is strongly associated with the large non-local deformation of the topological density distribution of coupled skyrmions. These results distinguish a skyrmion from other topological objects in dynamics and will be instrumental to the manipulation of skyrmions for applications. PMID- 25141994 TI - Between an uncomfortable decision and an absurd one. PMID- 25141995 TI - A uniform approach to the description of multicenter bonding. AB - A novel method for investigating the multicenter bonding patterns in molecular systems by means of the so-called Electron Density of Delocalized Bonds (EDDB) is introduced and discussed. The EDDB method combines the concept of Jug's bond order orbitals and the indirect ("through-bridge") interaction formalism and opens up new opportunities for studying the interplay between different atomic interactions as well as their impact on both local and global resonance stabilization in systems of conjugated bonds. Using several illustrative examples we demonstrate that the EDDB approach allows for a reliable quantitative description of diverse multicenter delocalization phenomena (with special regard to evaluation of the aromatic stabilization in molecular systems) within the framework of a consistent theoretical paradigm. PMID- 25141996 TI - The Hattie Hemschemeyer Award 2014: Judith S. Mercer, CNM, PhD, FACNM. PMID- 25141997 TI - Melanoma goes on a diet to get moving: toning down phagocytic Rab7 expression helps melanoma to metastasise. PMID- 25141998 TI - Establishment of opioid-induced rewarding effects under oxaliplatin- and Paclitaxel-induced neuropathy in rats. AB - The rewarding effects of MU-receptor agonists can be suppressed under several pain conditions. We recently showed that clinically used MU-receptor agonists possess efficacies for relieving the neuropathic pain induced by chemotherapeutic drug in rats; however, it is possible that the use of MU-receptor agonists may trigger the rewarding effects even under chemotherapeutic drug-induced neuropathic pain. Nevertheless, no information is available regarding whether MU receptor agonists produce psychological dependence under chemotherapeutic drug induced neuropathic pain. Therefore, we examined the effects of neuropathy induced by chemotherapeutic drugs on the rewarding effects of morphine, oxycodone, and fentanyl in rats. Repeated treatment with oxaliplatin or paclitaxel produced neuropathy as measured by the von Frey test. Rewarding effects produced by antinociceptive doses of MU-receptor agonists were not suppressed under oxaliplatin- or paclitaxel-induced neuropathy. Furthermore, the morphine-induced increase in the release of dopamine from the nucleus accumbens, which is a critical step in the rewarding effects of MU-receptor agonists, was not altered in paclitaxel-treated rats. These results suggest that the rewarding effects of MU-receptor agonists can still be established under oxaliplatin- or paclitaxel-induced neuropathic pain. Therefore, patients should be carefully monitored for psychological dependence on MU-receptor agonists when they are used to control chemotherapeutic drug-induced neuropathic pain. PMID- 25142000 TI - US dermatologists call for more oversight of nurse practitioners and physician assistants. PMID- 25141999 TI - Two Arabidopsis proteins synthesize acetylated xylan in vitro. AB - Xylan is the third most abundant glycopolymer on earth after cellulose and chitin. As a major component of wood, grain and forage, this natural biopolymer has far-reaching impacts on human life. This highly acetylated cell wall polysaccharide is a vital component of the plant cell wall, which functions as a molecular scaffold, providing plants with mechanical strength and flexibility. Mutations that impair synthesis of the xylan backbone give rise to plants that fail to grow normally because of collapsed xylem cells in the vascular system. Phenotypic analysis of these mutants has implicated many proteins in xylan biosynthesis; however, the enzymes directly responsible for elongation and acetylation of the xylan backbone have not been unambiguously identified. Here we provide direct biochemical evidence that two Arabidopsis thaliana proteins, IRREGULAR XYLEM 10-L (IRX10-L) and ESKIMO1/TRICOME BIREFRINGENCE 29 (ESK1/TBL29), catalyze these respective processes in vitro. By identifying the elusive xylan synthase and establishing ESK1/TBL29 as the archetypal plant polysaccharide O acetyltransferase, we have resolved two long-standing questions in plant cell wall biochemistry. These findings shed light on integral steps in the molecular pathways used by plants to synthesize a major component of the world's biomass and expand our toolkit for producing glycopolymers with valuable properties. PMID- 25142001 TI - Expression of the inhibitory Fc gamma receptor IIB (FCGR2B, CD32B) on follicular lymphoma cells lowers the response rate to rituximab monotherapy (SAKK 35/98). PMID- 25142002 TI - Safety and efficacy of ixmyelocel-T: an expanded, autologous multi-cellular therapy, in dilated cardiomyopathy. AB - RATIONALE: Ixmyelocel-T is associated with a wide range of biological activities relevant to tissue repair and regeneration. OBJECTIVE: To evaluate the safety and efficacy of ixmyelocel-T in 2 prospective randomized phase 2A Trials administered via minithoracotomy or intramyocardial catheter injections in patients with dilated cardiomyopathy (DCM) stratified by ischemic or nonischemic status. METHODS AND RESULTS: In IMPACT-DCM, patients were randomized to either ixmyelocel T or standard-of-care control in a 3:1 ratio (n=39); ixmyelocel-T was administered intramyocardially via minithoracotomy. In Catheter-DCM, patients were randomized to either ixmyelocel-T or standard of care control in a 2:1 ratio (n=22); ixmyelocel-T was administered intramyocardially using the NOGA Myostar catheter. Only patients randomized to ixmyelocel-T underwent bone marrow aspiration and injections. In the 2 studies, a total of 61 patients were randomized, and 59 were treated or received standard of care. Fewer ischemic patients treated with ixmyelocel-T experienced a major adverse cardiovascular event during follow-up when compared with control patients. A similar benefit was not seen in the nonischemic patients. Heart failure exacerbation was the most common major adverse cardiovascular event. Ixmyelocel-T treatment was associated with improved New York Heart Association class, 6-minute walk distance, and Minnesota Living with Heart Failure Questionnaire scores in the ischemic population relative to control; a similar trend was not observed in the nonischemic population. CONCLUSIONS: Intramyocardial injection with ixmyelocel-T reduces major adverse cardiovascular event and improves symptoms in patients with ischemic DCM but not in patients with nonischemic DCM. PMID- 25142003 TI - Tendon graft ossification: an unusual complication of suspensionplasty for trapeziometacarpal arthritis of the thumb. PMID- 25142004 TI - Radiographic diagnosis of dental restoration misfit: a systematic review. AB - The objective of this study was to perform a systematic review on the use of radiographic methods for the diagnosis of misfit in dental prostheses and restorations. The MEDLINE bibliographic database was searched from 1950 to February 2014 for reports on the radiographic diagnosis of misfits. The search strategy was limited to English-language publications using the following combined MeSH terms in the search strategy: (Dental Restoration OR Dental Prosthesis OR Crown OR Inlays OR Dental Abutments) and (Dental Leakage OR Prosthesis Fitting OR Dental Marginal Adaptation OR Surface Properties) and (Radiography, Dental OR Radiography, Dental, Digital OR Cone-Beam Computed Tomography). Twenty-eight publications were identified and read in full text, and 14 studies fulfilled criteria for inclusion. Information regarding the use of radiographic methods for the diagnosis of misfits in dental prosthesis and restorations, and in which the methodology/results comprised information regarding how the sample was collected/prepared, the method, imaging protocol, presence of a reference test and the outcomes were evaluated. QUADAS criteria was used to rate the studies in high, moderate or low quality. The evidence supporting the use of radiographic methods for the diagnosis of misfits in dental prosthesis and restorations is limited to low-/moderate-quality studies. The well established intra-oral orthogonal projection is still under investigation and considered the most appropriate method, both when evaluating the relation between dental restoration to tooth and abutment to implant. Studies using digital radiographs have not evaluated the effect of image post-processing, and tomography has not been evaluated. PMID- 25142007 TI - Beyond birthweight: the maternal and placental origins of chronic disease. AB - New findings on the maternal and placental programming of chronic disease lead to four conclusions: (1) Growth of the placental surface is polarized from the time of implantation, so that growth along the major axis, the length, is qualitatively different from growth along the minor axis, the breadth. (2) The human fetus may attempt to compensate for undernutrition by expansion of the placental surface along its minor axis. This only occurs if the mother was well nourished before conception, and may have long-term costs that include hypertension. (3) The effects of placental size on long-term health are conditioned by the mother's nutritional state, as indicated by her socio-economic status, height and body mass index. (4) The maternal-placental programming of chronic disease differs in boys and girls. Boys invest less than girls in placental growth but more readily expand the placental surface if they become undernourished in mid-late gestation. Boys are more responsive to their mothers' current diets while girls respond more to their mothers' lifetime nutrition and metabolism. PMID- 25142006 TI - US trends in receipt of appropriate diabetes clinical and self-care from 2001 to 2010 and racial/ethnic disparities in care. AB - PURPOSE: The purpose of this study was to examine trends in the receipt of 8 recommended diabetes clinical and self-care indicators from 2001 to 2010 and assess racial/ethnic disparities in care. METHODS: This observational study examined receipt of A1C tests, annual eye and foot exams, flu vaccination, diabetes self-management education (DSME), exercise, self-monitoring of blood glucose (SMBG), and self feet examinations among US adults with diabetes using national survey data from 2001 to 2010. Analyses included estimating proportions for each indicator by year, testing differences in magnitude of change from 2001 to 2010 by race/ethnicity, and regression models to assess changes in care over time and factors associated with care. RESULTS: There were significant increases from 2001 to 2010 in A1C tests, annual foot exams, flu shots, DSME, and SMBG but declines in eye and self feet exams. DSME was positively associated with receipt of several care indicators. However, only half of respondents received DSME. White and black non-Hispanics, respectively, experienced improvements in at least 3 indicators. Hispanics experienced a significant increase in exercise but were consistently less likely than whites to receive or engage in most care. CONCLUSIONS: While improvements in several indicators were observed, patterns varied by race/ethnicity, with Hispanics falling short on most measures. DSME was strongly associated with most care and demonstrates the potential to improve receipt of recommended care by increasing DSME participation. With the Affordable Care Act (ACA), health professionals have a prime opportunity to leverage ACA provisions to increase access to recommended services, including DSME. PMID- 25142008 TI - Effect of a low-protein diet during pregnancy on expression of genes involved in cardiac hypertrophy in fetal and adult mouse offspring. AB - Gene markers for cardiomyocyte growth, proliferation and remodeling were examined in mouse fetuses and adult male offspring exposed to maternal low-protein (LP) diet during pregnancy. Whole heart volume, measured by magnetic resonance imaging, was smaller in day 15 LP fetuses v. those from chow-fed dams (C), whereas heart volume was greater in adult LP v. C offspring. These LP offspring were hypertensive and had larger cardiomyocytes v. C animals. The mRNA levels of cyclin G1, a marker for cell growth, were lower in LP fetal hearts v. C hearts, but similar in the left ventricle of adult LP and C offspring. Opposite trends were found in brain natriuretic peptide levels (a marker of cardiac hypertrophy). Thus, maternal LP during pregnancy results in smaller fetal hearts and is accompanied by changes in expression of genes involved in cardiomyocyte growth, which are associated with cardiac hypertrophy and hypertension in adulthood. PMID- 25142005 TI - Specific aromatic foldamers potently inhibit spontaneous and seeded Abeta42 and Abeta43 fibril assembly. AB - Amyloid fibrils are self-propagating entities that spread pathology in several devastating disorders including Alzheimer's disease (AD). In AD, amyloid-beta (Abeta) peptides form extracellular plaques that contribute to cognitive decline. One potential therapeutic strategy is to develop inhibitors that prevent Abeta misfolding into proteotoxic conformers. Here, we design specific aromatic foldamers, synthetic polymers with an aromatic salicylamide (Sal) or 3-amino benzoic acid (Benz) backbone, short length (four repetitive units), basic arginine (Arg), lysine (Lys) or citrulline (Cit) side chains, and various N- and C-terminal groups that prevent spontaneous and seeded Abeta fibrillization. Ac Sal-(Lys-Sal)3-CONH2 and Sal-(Lys-Sal)3-CONH2 selectively inhibited Abeta42 fibrillization, but were ineffective against Abeta43, an overlooked species that is highly neurotoxic and frequently deposited in AD brains. By contrast, (Arg Benz)4-CONH2 and (Arg-Sal)3-(Cit-Sal)-CONH2 prevented spontaneous and seeded Abeta42 and Abeta43 fibrillization. Importantly, (Arg-Sal)3-(Cit-Sal)-CONH2 inhibited formation of toxic Abeta42 and Abeta43 oligomers and proteotoxicity. None of these foldamers inhibited Sup35 prionogenesis, but Sal-(Lys-Sal)3-CONH2 delayed aggregation of fused in sarcoma (FUS), an RNA-binding protein with a prion-like domain connected with amyotrophic lateral sclerosis and frontotemporal dementia. We establish that inhibitors of Abeta42 fibrillization do not necessarily inhibit Abeta43 fibrillization. Moreover, (Arg-Sal)3-(Cit-Sal)-CONH2 inhibits formation of toxic Abeta conformers and seeding activity, properties that could have therapeutic utility. PMID- 25142009 TI - Growth restriction before and after birth increases kinase signaling pathways in the adult rat heart. AB - To investigate the mechanisms for the previously reported development of adult cardiac hypertrophy in male rats following growth restriction, the levels of oxidative stress and activation of signaling kinases were measured in the left ventricle (LV) of adult rat offspring. In experiment one, bilateral uterine vessel ligation to induce uteroplacental insufficiency and growth restriction in the offspring (Restricted) or sham surgery was performed during pregnancy. Litters from sham mothers had litter size either reduced (Reduced Litter), which also restricted postnatal growth, or were left unaltered (Control). In males, Reduced Litter offspring had increased LV phosphorylation of AMPKalpha, p38 MAPK and Akt compared with Restricted and Controls (P < 0.05). In females, both Restricted and Reduced Litter adult offspring had increased LV phosphorylation of p38 MAPK and Akt, however, only Restricted offspring had increased phosphorylation of AMPKalpha (P < 0.05). In addition, only Restricted male offspring displayed LV oxidative stress (P < 0.05). Experiment two investigated in mothers exposed to uteroplacental insufficiency or sham surgery the effects of cross-fostering offspring at birth, and therefore the effects of the postnatal lactational environment. Surprisingly, the cross-fostering itself resulted in increased LV phosphorylation of AMPKalpha and Akt in females and increased phosphorylation of Akt in males compared with Control non-cross-fostered offspring (P < 0.05). In conclusion, kinase signaling in the adult LV can be programmed by uteroplacental insufficiency induced growth restriction in a gender specific manner. In addition, the heart of adult rats is also sensitive to programming following the postnatal intervention of cross-fostering alone as well as by postnatal growth restriction. PMID- 25142010 TI - Multivitamin supplementation during pregnancy alters body weight and macronutrient selection in Wistar rat offspring. AB - The hypothesis that vitamin content of the diet during gestation alters macronutrient choice, food intake and the expression of serotonin receptors and proopiomelanocortin (POMC) in the hypothalamus of the offspring was investigated. Pregnant Wistar rats (n = 10/group) were fed the AIN-93G diet containing a multivitamin mix at the recommended (RV) content or10-fold higher (high vitamin, HV) content. Male offspring were weaned to a choice of 10% and 60% casein diets. Intake regulation by the serotonergic system was determined by measuring food choice daily for 7 weeks, and following tryptophan (TRP) or mCPP (a serotonin receptor agonist) injections at 4 and 6 weeks post-weaning. mRNA expressions of hypothalamic serotonin receptor and POMC were measured at birth, weaning and sacrifice (7 weeks post-weaning). No differences were found in body weight at birth or weaning. HV offspring had lower food intake for the duration of the study (P < 0.001), and 11% lower body weight (P < 0.05) and 23% lower fat pad mass (P < 0.05) at 7 weeks post-weaning. They selected less protein following 12 h of food deprivation (P < 0.05) and were less responsive to TRP (P = 0.05) and mCPP (P < 0.05) injections at 6 weeks post-weaning. Expressions of mRNA for serotonin receptors 5-HT1A/2A/2C at weaning (P < 0.01) and of POMC at weaning and 7 weeks post-weaning (P < 0.05) were lower. In conclusion, intake of multivitamins above the requirements during pregnancy affected macronutrient choice, food intake and the expression of serotonin receptors and POMC in the hypothalamus. PMID- 25142011 TI - Analysis of compliance, morbidities and outcome in neurodevelopmental follow-up visits in urban African-American infants at environmental risk. AB - The objectives of this study were to determine compliance rate in a uniform, urban African-American patient population at environmental risk for adverse neurodevelopmental outcome and to define risk factors for non-compliance with neurodevelopmental follow-up. A retrospective chart review was performed which included 481 infants with birth weight (BW) of 495-4195 g and gestational ages (GAs) between 23 and 42 weeks born at our hospital. Statistical analysis was performed using the Jonckheere-Terpstra test for ordinal variables. For 2 * 2 tables, chi 2 test and Fisher's exact test (P < 0.05) were used. To determine significant predictive variables, data were analyzed by multiple logistic regression with one independent variable at a time. Infants compliant with follow up had significantly more morbidities in the very low BW category (?1500 g) than infants with larger BW. The highest compliance rate (70%) was found among the smallest and most immature (GA ?28 weeks) infants. Based on this finding, we postulate that the number of infants with severe disability is not likely to be underestimated. The significantly more frequent developmental anomalies found in the largest BW (?2500 g) category raises significant concern, though findings in this subset of infants may not be representative of the whole population. There was no significant difference between the compliant and non-compliant groups regarding socio-economic status. Severe or multiple morbidities and prolonged hospital stay may provide parents with greater opportunity to learn and understand about the infant's condition which may lead to greater compliance. PMID- 25142012 TI - Bigger babies born to women survivors of the 1959-1961 Chinese famine: a puzzle due to survival selection? AB - The Chinese Famine of 1959-1961 caused up to 30 million deaths. It varied in intensity across China and affected rural areas disproportionately. Data from the China-U.S. Collaborative Project for Neural Tube Defect Prevention on 31, 449 women (born 1957-1963) and their offspring birth size were recorded in 1993-1996. We used a measure of famine intensity at county level based on the size of famine born cohorts relative to cohorts preceding and following the famine in a difference-in-difference model that compared offspring birth size of pre-famine (1957-1958; exposed between 0.5 and 4.5 years), famine (1959-1961; prenatal and up to 2.5 years) and post-famine (1962; some exposed in early pregnancy) cohort groups to that of the unexposed 1963 cohort. The model corrected for age and cohort trends and estimated associations between maternal famine exposure and offspring birth size for the average level of famine intensity across counties, and included adjustment for clustering. In rural areas and in pre-famine and famine cohorts, exposure to famine was associated with larger weight (69 g; 95% CI 30, 108), length (0.3 cm; 95% CI -0.0, 0.5) and birth body mass index (0.1 kg/m2; 95% CI 0.0, 0.2). In urban areas, however, exposure to famine was not associated with offspring birth size. Our findings in rural areas suggest that severe and prolonged famine leads to larger newborn size in the offspring of mothers exposed to famine in utero and during the first few years of life; less severe famine in urban areas however, appeared to have no impact. The markedly increased mortality in rural areas may have resulted in the selection of hardier mothers with greater growth potential, which becomes expressed in their offspring. PMID- 25142013 TI - Large-scale study suggests specific indicators for combined cognitive therapy and pharmacotherapy in major depressive disorder. PMID- 25142014 TI - Optimized determination of polybrominated diphenyl ethers by ultrasound-assisted liquid-liquid extraction and high-performance liquid chromatography. AB - A method based on ultrasound-assisted liquid-liquid extraction and high performance liquid chromatography has been optimized for the determination of six polybrominated diphenyl ether congeners. The optimal condition relevant to the extraction was first investigated, more than 98.7 +/- 0.7% recovery was achieved with dichloromethane as extractant, 5 min extraction time, and three cycles of ultrasound-assisted liquid-liquid extraction. Then multiple function was employed to optimize polybrominated diphenyl ether detection conditions with overall resolution and chromatography signal area as the responses. The condition chosen in this experiment was methanol/water 93:7 v/v, flow rate 0.80 mL/min, column temperature 30.0 degrees C. The optimized technique revealed good linearity (R(2) > 0.9962 over a concentration range of 1-100 MUg/L) and repeatability (relative standard deviation < 6.3%). Furthermore, the detection limit (S/N = 3) of the method were ranged from 0.02 to 0.13 MUg/L and the quantification limit (S/N = 10) ranged from 0.07 to 0.35 MUg/L. Finally, the proposed method was applied to spiked samples and satisfactory results were achieved. These results indicate that ultrasound-assisted liquid-liquid extraction coupled with high-performance liquid chromatography was effective to identify and quantify the complex polybrominated diphenyl ethers in effluent samples. PMID- 25142015 TI - Fibroblast extracellular matrix and adhesion on microtextured polydimethylsiloxane scaffolds. AB - The immediate physical and chemical surroundings of cells provide important biochemical cues for their behavior. Designing and tailoring biomaterials for controlled cell signaling and extracellular matrix (ECM) can be difficult due to the complexity of the cell-surface relationship. To address this issue, our research has led to the development of a polydimethylsiloxane (PDMS) scaffold with defined microtopography and chemistry for surface driven ECM assembly. When human fibroblasts were cultured on this microtextured PDMS with 2-6 um wide vertical features, significant changes in morphology, adhesion, actin cytoskeleton, and fibronectin generation were noted when compared with cells cultured on unmodified PDMS. Investigation of cellular response and behavior was performed with atomic force microscopy in conjunction with fluorescent labeling of focal adhesion cites and fibronectin in the ECM. Changes in the surface topography induced lower adhesion, an altered actin cytoskeleton, and compacted units of fibronectin similar to that observed in vivo. Overall, these findings provide critical information of cell-surface interactions with a microtextured, polymer substrate that can be used in the field of tissue engineering for controlling cellular ECM interactions. PMID- 25142016 TI - Altered microglial phagocytosis in GPR34-deficient mice. AB - GPR34 is a Gi/o protein-coupled receptor (GPCR) of the nucleotide receptor P2Y12 like group. This receptor is highly expressed in microglia, however, the functional relevance of GPR34 in these glial cells is unknown. Previous results suggested an impaired immune response in GPR34-deficient mice infected with Cryptococcus neoformans. Here we show that GPR34 deficiency results in morphological changes in retinal and cortical microglia. RNA sequencing analysis of microglia revealed a number of differentially expressed transcripts involved in cell motility and phagocytosis. We found no differences in microglial motility after entorhinal cortex lesion and in response to laser lesion. However, GPR34 deficient microglia showed reduced phagocytosis activity in both retina and acutely isolated cortical slices. Our study identifies GPR34 as an important signaling component controlling microglial function, morphology and phagocytosis. PMID- 25142017 TI - Myeloid-derived suppressor cell functionality and interaction with Leishmania major parasites differ in C57BL/6 and BALB/c mice. AB - Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of CD11b+ cells. According to the surface molecules Ly6G and Ly6C (where Ly6G and Ly6C are lymphocyte antigen 6, locus G and C, respectively), MDSCs are further divided into monocytic (Mo-MDSCs, CD11b+ /Ly6C(high) /Ly6G-) and polymorphonucleated suppressor cells (PMN-MDSCs, CD11b+ /Ly6C(int) /Ly6G+). Most published manuscripts focus on the suppressive role of MDSCs in cancer, whereas their impact on adaptive immunity against obligatory intracellular parasites is not well understood. Furthermore, it is not clear how the genetic background of mice influences MDSC functionality. Therefore, we implemented an experimental model of leishmaniasis, and analyzed MDSC maturation and the impact of MDSCs on the parasite-specific T-cell responses in resistant C57BL/6 and susceptible BALB/c mice. This experimental setup demonstrated the impaired ability of BALB/c mice to produce Mo-MDSCs when compared with C57BL/6 mice. This phenotype is detectable after subcutaneous infection with parasites and is specifically represented by a reduced accumulation of Mo-MDSCs at the site of infection in BALB/c mice. Moreover, infected C57BL/6-derived MDSCs were able to suppress Leishmania-specific CD4+ -cell proliferation, whereas BALB/c-derived MDSCs harboring parasites lost this suppressive function. In conclusion, we demonstrate that (i) genetic background defines MDSC differentiation; and (ii) Leishmania major parasites are able to modulate the suppressive effect of MDSCs in a strain dependent manner. PMID- 25142018 TI - Negative, neutral, and positive interactions among nonnative plants: patterns, processes, and management implications. AB - The movement of species is one of the most pervasive forms of global change, and few ecosystems remain uninvaded by nonnative species. Studying species interactions is crucial for understanding their distribution and abundance, particularly for nonnative species because interactions may influence the probability of invasion and consequent ecological impact. Interactions among nonnatives are relatively understudied, though the likelihood of nonnative species co-occurrence is high. We quantify and describe the types of interactions among nonnative plants and determine what factors affect interaction outcomes for ecosystems globally. We reviewed 65 studies comprising 201 observations and recorded the interaction type, traits of the interacting species, and study characteristics. We conducted a census of interaction types and a meta-analysis of experiments that tested nonnative competition intensity. Both methods showed that negative and neutral interactions prevailed, and a number of studies reported that the removal of a dominant nonnative led to competitive release of other nonnatives. Positive interactions were less frequently reported and positive mean effect sizes were rare, but the plant characteristics nitrogen fixation, life cycle (annual or perennial), and functional group significantly influenced positive interactions. Positive interactions were three times more frequent when a neighboring nonnative was a nitrogen fixer and 3.5 times lower when a neighboring nonnative was an annual. Woody plants were two or four times more likely to have positive interactions relative to grasses or herbs, respectively. The prevalence of negative interactions suggests that managers should prepare for reinvasion of sites when treating dominant nonnatives. Though positive interactions were infrequent, managers may be able to anticipate positive interactions among nonnatives based upon traits of the co-occurring invaders. Predicting positive nonnative interactions is an important tool for determining habitat susceptibility to a particular invasion and for prioritizing management of nonnatives with a higher likelihood of positive interactions. PMID- 25142019 TI - Fluorescence resonance energy transfer between green fluorescent protein and doxorubicin enabled by DNA nanotechnology. AB - DNA nanotechnology is a rapidly growing research area, where DNA may be used for wide range of applications such as construction of nanodevices serving for large scale of diverse purposes. Likewise a panel of various purified fluorescent proteins is investigated for their ability to emit their typical fluorescence spectra under influence of particular excitation. Hence these proteins may form ideal donor molecules for assembly of fluorescence resonance emission transfer (FRET) constructions. To extend the application possibilities of fluorescent proteins, while using DNA nanotechnology, we developed nanoconstruction comprising green fluorescent protein (GFP) bound onto surface of surface active nanomaghemite and functionalized with gold nanoparticles. We took advantage of natural affinity between gold and thiol moieties, which were modified to bind DNA fragment. Finally we enclosed doxorubicin into fullerene cages. Doxorubicin intercalated in DNA fragment bound on the particles and thus we were able to connect these parts together. Because GFP behaved as a donor and doxorubicin as an acceptor using excitation wavelength for GFP (395 nm) in emission wavelength of doxorubicin (590 nm) FRET was observed. This nanoconstruction may serve as a double-labeled transporter of doxorubicin guided by force of external magnetic force owing to the presence of nanomaghemite. Further nanomaghemite offers the possibility of using this technology for thermotherapy. PMID- 25142020 TI - ATF4 and N-Myc coordinate glutamine metabolism in MYCN-amplified neuroblastoma cells through ASCT2 activation. AB - Amplification of the MYCN gene in human neuroblastoma predicts poor prognosis and resistance to therapy. We previously showed that MYCN-amplified neuroblastoma cells constantly require large amounts of glutamine to support their unabated growth. However, the identity and regulation of the transporter(s) that capture glutamine in MYCN-amplified neuroblastoma cells and the clinical significance of the transporter(s) in neuroblastoma diagnosis remain largely unknown. Here, we performed a systemic glutamine influx analysis and identified that MYCN-amplified neuroblastoma cells predominantly rely on activation of ASCT2 (solute carrier family 1 member 5, SLC1A5) to maintain sufficient levels of glutamine essential for the TCA cycle anaplerosis. Consequently, ASCT2 depletion profoundly inhibited glutaminolysis, concomitant with a substantial decrease in cell proliferation and viability in vitro and inhibition of tumourigenesis in vivo. Mechanistically, we identified ATF4 as a novel regulator which coordinates with N-Myc to directly activate ASCT2 expression. Of note, ASCT2 expression, which correlates with that of N-Myc and ATF4, is markedly elevated in high-stage neuroblastoma tumour samples compared with low-stage ones. More importantly, high ASCT2 expression is significantly associated with poor prognosis and survival of neuroblastoma patients. In aggregate, these findings elucidate a novel mechanism depicting how cell autonomous insults (MYCN amplification) and microenvironmental stresses (ATF4 induction) in concert coordinate ASCT2 activation to promote aggressive neuroblastoma progression, and establish ASCT2 as a novel biomarker in patient prognosis and stratification. PMID- 25142021 TI - Leishmania amazonensis infection impairs dendritic cell migration from the inflammatory site to the draining lymph node. AB - BACKGROUND: In vitro studies show that Leishmania infection decreases the adhesion of inflammatory phagocytes to connective tissue by a mechanism dependent on the modulation of integrin function. However, we know little about the influence of this reduction in leukocyte adhesion on parasite dissemination from the infection site. METHODS: In this work, we used a model of chronic peritonitis induced by thioglycollate to study the effect of L. amazonensis infection on the ability of inflammatory phagocyte populations to migrate from an inflammatory site to the draining lymph node. Uninfected or Leishmania-infected thioglycollate elicited peritoneal exudate cells were transferred from C57BL/6 to BALB/c mice or from Ly5.1+ to Ly5.1- mice. The transferred cells were injected into the peritoneal cavity and tracked to the draining lymph node. RESULTS: Migrating cells corresponded to approximately 1% of the injected leukocytes. The proportion of migrating CD11b+CD11c+ (myeloid dendritic cell) was lower after incubation with Leishmania (1.3 to 2.6 times lower in the experiments using C57BL/6 to BALB/c animals and 2.7 to 3.4 times lower in the experiments using Ly5.1+ to Ly5.1- animals) than after leukocyte incubation with medium alone (P < 0.01). There was no consistent decrease in the migration of CD11b+F4/80+ (macrophage) or SSChi GR-1+ (neutrophil) populations. CONCLUSIONS: Coincubation with Leishmania changes the migratory pattern of dendritic cells in vivo. Such changes in dendritic cell migration may be associated with immunological events that maintain inflammation at the sites of infection. PMID- 25142023 TI - Detection of c-reactive protein based on a magnetic immunoassay by using functional magnetic and fluorescent nanoparticles in microplates. AB - We report the preparation and application of biofunctional nanoparticles to detect C-reactive protein (CRP) in magnetic microplates. A CRP model biomarker was used to test the proposed detection method. Biofunctional magnetic nanoparticles, CRP, and biofunctional fluorescent nanoparticles were used in a sandwich nanoparticle immunoassay. The CRP concentrations in the samples were deduced from the reference plot, using the fluorescence intensity of the sandwich nanoparticle immunoassay. When biofunctional nanoparticles were used to detect CRP, the detection limit was 1.0 ng ml(-1) and the linear range was between 1.18 ng ml(-1) and 11.8 MUg ml(-1). The results revealed that the method involving biofunctional nanoparticles exhibited a lower detection limit and a wider linear range than those of the enzyme-linked immunosorbent assay (ELISA) and most other methods. For CRP measurements of serum samples, the differences between this method and ELISA in CRP measurements of serum samples were less than 13%. The proposed method can reduce the analysis time to one-third that of ELISA. This method demonstrates the potential to replace ELISA for rapidly detecting biomarkers with a low detection limit and a wide dynamic range. PMID- 25142022 TI - Targeting mitochondria with methylene blue protects mice against acetaminophen induced liver injury. AB - Acetaminophen (APAP) overdose is a frequent cause of drug-induced liver injury and the most frequent cause of acute liver failure in the Western world. Previous studies with mouse models have revealed that impairment of mitochondrial respiration is an early event in the pathogenesis, but the exact mechanisms have remained unclear, and therapeutic approaches to specifically target mitochondria have been insufficiently explored. Here, we found that the reactive oxidative metabolite of APAP, N-acetyl-p-benzoquinoneimine (NAPQI), caused the selective inhibition of mitochondrial complex II activity by >90% in both mouse hepatic mitochondria and yeast-derived complexes reconstituted into nanoscale model membranes, as well as the decrease of succinate-driven adenosine triphosphate (ATP) biosynthesis rates. Based on these findings, we hypothesized that methylene blue (MB), a mitochondria-permeant redox-active compound that can act as an alternative electron carrier, protects against APAP-induced hepatocyte injury. We found that MB (<3 uM) readily accepted electrons from NAPQI-altered, succinate energized complex II and transferred them to cytochrome c, restoring ATP biosynthesis rates. In cultured mouse hepatocytes, MB prevented the mitochondrial permeability transition and loss of intracellular ATP without interfering with APAP bioactivation. In male C57BL/6J mice treated with APAP (450 mg/kg, intraperitoneally [IP]), MB (10 mg/kg, IP, administered 90 minutes post-APAP) protected against hepatotoxicity, whereas mice treated with APAP alone developed massive centrilobular necrosis and increased serum alanine aminotransferase activity. APAP treatment inhibited complex II activity ex vivo, but did not alter the protein expression levels of subunits SdhA or SdhC after 4 hours. CONCLUSION: MB can effectively protect mice against APAP-induced liver injury by bypassing the NAPQI-altered mitochondrial complex II, thus alleviating the cellular energy crisis. Because MB is a clinically used drug, its potential application after APAP overdose in patients should be further explored. PMID- 25142025 TI - Know versus Familiar: Differentiating states of awareness in others' subjective reports of recognition. AB - In the Remember-Know paradigm whether a Know response is defined as a high confidence state of certainty or a low-confidence state based on familiarity varies across researchers and can influence participants' responses. The current experiment was designed to explore differences between the states of Know and Familiar. Participants studied others' justification statements to "Know" recognition decisions and separated them into two types. Crucially, participants were not provided definitions of Know and Familiar on which to sort the items- their judgements were based solely on the phenomenology described in the justifications. Participants' sorting decisions were shown to reliably map onto expert classification of Know and Familiar. Post-task questionnaire responses demonstrated that both the level of memory detail and confidence expressed in the justifications were central to how participants categorised the items. In sum, given no instructions to do so, participants classify Familiar and Know according to two dimensions: confidence and amount of information retrieved. PMID- 25142024 TI - High-fat diet reduces neuroprotection of isoflurane post-treatment: Role of carboxyl-terminal modulator protein-Akt signaling. AB - OBJECTIVE: High-fat diet (HFD) contributes to the increased prevalence of obesity and hyperlipidemia in young adults, a possible cause for their recent increase in stroke. Isoflurane post-treatment provides neuroprotection. Isoflurane post treatment induced neuroprotection in HFD-fed mice was determined. METHODS: Six week old CD-1 male mice were fed HFD or regular diet (RD) for 5 or 10 weeks. Their hippocampal slices (400 um) were subjected to oxygen-glucose deprivation (OGD). Some slices were exposed to isoflurane for 30 min immediately after OGD. Some mice had a 90-min middle cerebral arterial occlusion and were post-treated with 2% isoflurane for 30 min. RESULTS: OGD time-dependently induced cell injury. This injury was dose-dependently reduced by isoflurane. The effect was apparent at 1% or 2% isoflurane in RD-fed mice but required 3% isoflurane in HFD-fed mice. HFD influenced the isoflurane effects in DG. OGD increased carboxyl-terminal modulator protein (CTMP), an Akt inhibitor, and decreased Akt signaling. Isoflurane reduced these effects. LY294002, an Akt activation inhibitor, attenuated the isoflurane effects. HFD increased CTMP and reduced Akt signaling. Isoflurane improved neurological outcome in the RD-fed mice but not in the HFD fed mice. CONCLUSIONS: HFD attenuated isoflurane post-treatment-induced neuroprotection possibly because of decreased prosurvival Akt signaling. PMID- 25142026 TI - Random mutagenesis and media optimisation for hyperproduction of cellulase from Bacillus species using proximally analysed Saccharum spontaneum in submerged fermentation. AB - This study deals with the isolation of novel mutant of Bacillus and optimisation of media for the hyperproduction of cellulase. Cellulase-producing Bacillus PC BC6 was subjected to physical and chemical mutagenesis to enhance the cellulolytic potential. Later, mutagenesis isolates were screened both qualitatively and quantitatively. Among all the tested isolates, Bacillus N3 yielded maximum (CMCase 1250 IU/mL/min and FPase 629 IU/mL/min) activity. The Bacillus N3 strain exhibited 1.7-fold more enzyme production as compared with the parental strain. Proximate analysis of untreated and pretreated Saccharum spontaneum was carried out to improve cellulase production. Three different media were tested for the production of cellulase, among which M2 medium containing MgSO4, pretreated S. spontaneum, K2HPO4, (NH4)2SO4 and peptone was found to be the best for maximum enzyme production by mutant Bacillus N3. PMID- 25142027 TI - Expansion of a 2 + 2 macrocycle into a 6 + 6 macrocycle: template effect of cadmium(II). AB - The reaction of trans-1,2-diaminocyclopentane with 2,6-diformylpyridine results in formation of 2 + 2, 3 + 3, and 4 + 4 Schiff base macrocycles as well as trace amounts of 6 + 6 and 8 + 8 macrocycles. In contrast, the 6 + 6 Schiff base macrocycle is a dominant product of the reaction of the isolated 2 + 2 macrocycle with excess of cadmium(II) chloride. The X-ray crystal structure of the protonated amine derivative of the 6 + 6 macrocycle reveals an unusual container like conformation with the S6 axis. PMID- 25142028 TI - Monodisperse carboxyl-functionalized poly(ethylene glycol)-coated magnetic poly(glycidyl methacrylate) microspheres: application to the immunocapture of beta-amyloid peptides. AB - Identification and evaluation of small changes in beta-amyloid peptide (Abeta) levels in cerebrospinal fluid is of crucial importance for early detection of Alzheimer's disease. Microfluidic detection methods enable effective preconcentration of Abeta using magnetic microparticles coated with Abeta antibodies. Poly(glycidyl methacrylate) microspheres are coated with alpha-amino omega-methoxy-PEG5000 /alpha-amino-omega-Boc-NH-PEG5000 Boc groups deprotected and NH2 succinylated to introduce carboxyl groups. Capillary electrophoresis with laser-induced fluorescence detection confirms the efficient capture of Abeta 1-40 peptides on the microspheres with immobilized monoclonal anti-Abeta 6E10. The capture specificity is confirmed by comparing Abeta 1-40 levels on the anti-IgG immobilized particles used as a control. PMID- 25142029 TI - Thermal limits of two biting midges, Culicoides imicola Kieffer and C. bolitinos Meiswinkel (Diptera: Ceratopogonidae). AB - BACKGROUND: Culicoides imicola Kieffer and Culicoides bolitinos Meiswinkel (Diptera: Ceratopogonidae) are both of veterinary importance, being vectors of Schmallenberg, bluetongue and African horse sickness (AHS) viruses. Within South Africa, these Culicoides species show a marked difference in their abundances according to altitude, with C. imicola highly abundant in lower altitudes, but being replaced as the dominant species by C. bolitinos in cooler, high-altitude regions. METHODS: The thermal physiology of field collected adults of each species was determined to evaluate whether it could account for differences in their distribution and abundance. Critical thermal maxima (CTmax) and minima (CTmin), as well as upper and lower lethal temperatures (ULT and LLT) were assessed after acclimation temperatures of 19'C, 24'C and 29'C. Critical thermal limits were determined using an ecologically relevant rate of temperature change of 0.06'C x min(-1). RESULTS: Significant differences in CTmin and CTmax were found between acclimation temperatures for C. imicola and C. bolitinos. In C. bolitinos, the LLT of individuals acclimated at 24'C was significantly improved (LLT50 = -6.01'C) compared with those acclimated at the other temperatures (LLT50 = -4'C). Acclimation had a weak (difference in LLT50 of only 1'C) but significant effect on the LLT of C. imicola. When CTmin, CTmax, LLT and ULT were superimposed on daily maximum and minimum temperature records from locations where each tested Culicoides species is dominant, it was found that temperatures frequently declined below the CTmin and LLT of C. imicola at the location where C. bolitinos was dominant. CONCLUSIONS: The distribution and abundance of C. imicola is likely directly constrained by their relatively poor tolerance of lower temperatures. Results for C. bolitinos suggest that the adult phase is hardy, and it is hypothesised that the thermal biology of other life stages could determine their range. PMID- 25142030 TI - A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane. AB - Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels carry Ih, which contributes to neuronal excitability and signal transmission in the nervous system. Controlling the trafficking of HCN1 is an important aspect of its regulation, yet the details of this process are poorly understood. Here, we investigated how the C-terminus of HCN1 regulates trafficking by testing for its ability to redirect the localization of a non-targeted reporter in transgenic Xenopus laevis photoreceptors. We found that HCN1 contains an ER localization signal and through a series of deletion constructs, identified the responsible di arginine ER retention signal. This signal is located in the intrinsically disordered region of the C-terminus of HCN1. To test the function of the ER retention signal in intact channels, we expressed wild type and mutant HCN1 in HEK293 cells and found this signal negatively regulates surface expression of HCN1. In summary, we report a new mode of regulating HCN1 trafficking: through the use of a di-arginine ER retention signal that monitors processing of the channel in the early secretory pathway. PMID- 25142031 TI - Genetic associations and functional characterization of M1 aminopeptidases and immune-mediated diseases. AB - Endosplasmic reticulum aminopeptidase 1 (ERAP1), endoplasmic reticulum aminopeptidase 2 (ERAP2) and puromycin-sensitive aminopeptidase (NPEPPS) are key zinc metallopeptidases that belong to the oxytocinase subfamily of M1 aminopeptidase family. NPEPPS catalyzes the processing of proteosome-derived peptide repertoire followed by trimming of antigenic peptides by ERAP1 and ERAP2 for presentation on major histocompatibility complex (MHC) Class I molecules. A series of genome-wide association studies have demonstrated associations of these aminopeptidases with a range of immune-mediated diseases such as ankylosing spondylitis, psoriasis, Behcet's disease, inflammatory bowel disease and type I diabetes, and significantly, genetic interaction between some aminopeptidases and HLA Class I loci with which these diseases are strongly associated. In this review, we highlight the current state of understanding of the genetic associations of this class of genes, their functional role in disease, and potential as therapeutic targets. PMID- 25142033 TI - Lung ultrasonography: an effective way to diagnose community-acquired pneumonia. AB - PURPOSE: To analyse the ultrasonographic findings of community-acquired pneumonia (CAP) and its efficacy for diagnosis of CAP compared with chest X-ray (CXR). METHODS: Patients who presented to the Emergency Department with suspected CAP were included in the study. Bedside ultrasonography was performed at each intercostal space in the midclavicular, anterior axillary, midaxillary and paravertebral lines. Any pulmonary consolidation, focal interstitial pattern, pleural-line abnormalities and subpleural lesions were recorded, and the numbers of subpleural lesions and intercostal spaces with pleural-line abnormalities were counted. All patients received bedside CXR and CT. Using CT scan as the gold standard, ultrasonography findings were compared between CAP group and non-CAP group, and between CAP patients with CT showing consolidation or diffuse ground glass opacification. The sensitivity of ultrasonography was compared with CXR for the diagnosis of CAP. RESULTS: Of 179 patients included in the study, 112 were diagnosed with CAP by CT. Patients in CAP group were more likely to have consolidation (p<0.001), focal interstitial pattern (p<0.001) and had higher number of subpleural lesions (p<0.001) and intercostal spaces with pleural-line abnormalities (p<0.001) on ultrasound than those without CAP. CAP patients whose CT showed consolidation were more likely to have consolidation (p<0.001) and had lower numbers of subpleural lesions (p<0.001) and intercostal spaces with pleural line abnormalities (p<0.001) compared to CAP patients whose CT showed diffuse ground-glass opacification. The diagnostic sensitivity, specificity, and accuracy for ultrasonography and CXR were 94.6% versus 77.7% (p<0.001), 98.5% versus 94.0% (p=0.940) and 96.1% versus 83.8% (p<0.001), respectively. CONCLUSIONS: Lung ultrasonography has a better diagnostic sensitivity and accuracy for diagnosing CAP compared with CXR. PMID- 25142032 TI - Recombinant porcine epidermal growth factor-secreting Lactococcus lactis promotes the growth performance of early-weaned piglets. AB - BACKGROUND: Epidermal growth factor (EGF) is an important growth factor in regulation of cell proliferation, differentiation, survival and apoptosis. Studies showed that food-grade Lactococcus lactis (L. lactis) and NICE expression system have superior performance in exogenous protein expression. This study aimed to construct and express porcine EGF (pEGF), and use L. lactis as vehicle for producing and delivering pEGF. Furthermore, investigating biological activity of pEGF and exploring applications feasibility of combination effects of L. lactis and pEGF on early weaned piglets' production. RESULTS: A recombinant Lactococcus lactis which produced and secreted pEGF at 1000 ng/ml in culture supernatant was generated. Secreted pEGF was a fully biologically active protein, as demonstrated by its capacity to stimulate L929 mouse fibroblast cell line proliferation in vitro. For in vivo study, forty piglets were randomly allocated to control, antibiotic control, empty vector-expressing L. lactis (LL-EV) and pEGF-secreting L. lactis (LL-pEGF). After 14 d of rearing, final body weight and average daily gain in LL-pEGF were greater (P < 0.05, 8.95 vs. 8.37 kg, 206.1 vs. 157.7 g/day, respectively) than those in control, but no significant differences between LL-pEGF, LL-EV and antibiotic control. Overall period average daily feed intake was higher in LL-pEGF, LL-EV and antibiotic control than in control (P < 0.05, 252.9, 255.6, 250.0, 207.3 g/day, respectively). No significant difference was observed on ADFI/ADG. LL-pEGF increased villous height in the duodenum, jejunum and ileum than in control and LL-EV (P < 0.05). Sucrase in the 3 intestinal segments, aminopeptidase A in the duodenum and Jejunum, aminopeptidase N and dipeptidase IV in the duodenum in LL-pEGF were higher than those in control (P < 0.05). Furthermore, Escherichia coli and Enterococcus counts decreased in the ileum and Lactobacillus increased in the ileum and cecum digesta in LL-pEGF compare with the control (P < 0.05). Lactobacillus increased in the cecum in LL EV compared with control and antibiotic control (P < 0.05). CONCLUSION: We have generated a recombinant Lactococcus lactis which produced and secreted fully biologically active porcine EGF. Oral administration of pEGF-secreting L. lactis had beneficial effects on intestinal health and performance of early-weaned piglets. PMID- 25142034 TI - Diagnostic accuracy of lateral neck radiography in ruling out supraglottitis: a prospective observational study. AB - OBJECTIVE: To assess the diagnostic accuracy of lateral neck radiographs (LNR) for acute supraglottitis in adults. DESIGN: A single centre prospective observational study. SETTING: Emergency department at Kurashiki Central Hospital, Japan. PARTICIPANTS: Adult patients who underwent LNR to detect supraglottitis. MAIN OUTCOME MEASURES: Presence of supraglottitis, based on nasopharyngeal laryngoscopy or a follow-up telephone call, 7-30 days after the visit. RESULTS: 140 patients had LNR during the study period. 35 patients were excluded from further analysis because of lack of consent. Of the 105 eligible patients, 21 patients (20%) were given the diagnosis of supraglottitis: 17 of 29 with a radiographic abnormality, and 4 of 76 patients without a radiographic abnormality. Three of the four cases where LNR was negative was grade 1, and all cases of grade 3 or higher had abnormal LNR. Sensitivity and specificity (95% CI) of LNR for supraglottitis were 81.0% (64.2 to 97.7) and 85.7% (78.2 to 93.2), respectively. The positive predictive value of LNR was 58.6% (40.7 to 76.5) and the negative predictive value was 94.7% (89.7 to 99.8). The positive likelihood ratio of LNR was 5.67 (3.27 to 9.82) and the negative likelihood ratio was 0.22 (0.10 to 0.51). CONCLUSIONS: LNR showed only moderate sensitivity and specificity for supraglottitis and would miss some cases of supraglottitis if the pre-test probability is high. LNR was very sensitive for grade 3 or higher supraglottitis, but would miss milder cases. TRIAL REGISTRATION: UMIN000011928. PMID- 25142035 TI - Measuring decision quality: psychometric evaluation of a new instrument for breast cancer chemotherapy. AB - BACKGROUND: Women diagnosed with early stage (I or II) breast cancer face a highly challenging decision - whether or not to undergo adjuvant chemotherapy. We developed a decision quality instrument for chemotherapy for early stage breast cancer and sought to evaluate its performance. METHODS: Cross-sectional, mailed survey of recent breast cancer survivors, providers, and healthy controls and a retest survey of survivors. The decision quality instrument includes questions on knowledge and personal goals. It results in a knowledge score and concordance score, which reflects the percentage of patients who received treatments that match their goals. Hypotheses related to acceptability, feasibility, validity, and reliability of the survey instrument were examined. RESULTS: Responses were received from 352 patients, 89 providers and 35 healthy controls. The decision quality instrument was feasible to implement with few missing data. The knowledge scores had good retest reliability (intraclass correlation coefficient (ICC) =0.75). Knowledge scores discriminated between providers and patients (mean difference 31.1%, 95% CI 26.9, 35.3) and between patients and healthy controls (mean difference 11.2, 95% CI 5.4, 17.1). Most providers reported that the knowledge items covered essential content. Two of the five goal items had a ceiling effect, and one goal had low content validity. The goal items had moderate retest reliability (ICC's 0.57 to 0.78). In the multivariable model of treatment, none of the patient goals was associated with receipt of chemotherapy. Age and hormone receptor status were the only variables independently associated with chemotherapy. Most patients (77.6%) had treatment concordant with that predicted by the model. Patients who had concordant treatment had similar levels of confidence and regret as those who did not. CONCLUSIONS: The Decision Quality Instrument is a reliable and valid measure of patient knowledge about chemotherapy, but its ability to measure concordance with patient goals is limited. In this sample, patient goals were not associated with treatment, and most patients reported they were not asked their preference, suggesting that goals were not adequately considered in decision making. PMID- 25142036 TI - Biomarkers of sepsis and their potential value in diagnosis, prognosis and treatment. AB - Biomarkers have great potential to improve the diagnosis and treatment of sepsis. The available literature supports the potential utility of sTREM-1, IL-27, suPAR, neutrophil CD64, presepsin, cfDNA and miRNAs as novel diagnostic, prognostic and treatment response biomarkers. The future of sepsis biomarkers lies in extensive validation studies of such novel biomarkers across heterogeneous populations and exploration of their power in combination. Furthermore, the use of a companion diagnostics model may augment the ability of investigators to identify novel sepsis biomarkers and develop specific therapeutic strategies based on biomarker information. PMID- 25142037 TI - Informing the scale-up of Kenya's nursing workforce: a mixed methods study of factors affecting pre-service training capacity and production. AB - BACKGROUND: Given the global nursing shortage and investments to scale-up the workforce, this study evaluated trends in annual student nurse enrolment, pre service attrition between enrolment and registration, and factors that influence nurse production in Kenya. METHODS: This study used a mixed methods approach with data from the Regulatory Human Resources Information System (tracks initial student enrolment through registration) and the Kenya Health Workforce Information System (tracks deployment and demographic information on licensed nurses) for the quantitative analyses and qualitative data from key informant interviews with nurse training institution educators and/or administrators. Trends in annual student nurse enrolment from 1999 to 2010 were analyzed using regulatory and demographic data. To assess pre-service attrition between training enrolment and registration with the nursing council, data for a cohort that enrolled in training from 1999 to 2004 and completed training by 2010 was analyzed. Multivariate logistic regression was used to test for factors that significantly affected attrition. To assess the capacity of nurse training institutions for scale-up, qualitative data was obtained through key informant interviews. RESULTS: From 1999 to 2010, 23,350 students enrolled in nurse training in Kenya. While annual new student enrolment doubled between 1999 (1,493) and 2010 (3,030), training institutions reported challenges in their capacity to accommodate the increased numbers. Key factors identified by the nursing faculty included congestion at clinical placement sites, limited clinical mentorship by qualified nurses, challenges with faculty recruitment and retention, and inadequate student housing, transportation and classroom space. Pre-service attrition among the cohort that enrolled between 1999 and 2004 and completed training by 2010 was found to be low (6%). CONCLUSION: To scale-up the nursing workforce in Kenya, concurrent investments in expanding the number of student nurse clinical placement sites, utilizing alternate forms of skills training, hiring more faculty and clinical instructors, and expanding the dormitory and classroom space to accommodate new students are needed to ensure that increases in student enrolment are not at the cost of quality nursing education. Student attrition does not appear to be a concern in Kenya compared to other African countries (10 to 40%). PMID- 25142038 TI - Susac-like syndrome in a chronic cocaine abuser: could levamisole play a role? AB - INTRODUCTION: Toxic leukoencephalopathy is a possible but rare complication of chronic cocaine abuse. The role of adulterants, mainly levamisole, is still debated. CASE REPORT: We describe an atypical case of fatal leukoencephalopathy mimicking Susac syndrome in a 22-year-old man who was chronically abusing cannabis and cocaine. Exposure to levamisole as adulterant to cocaine was proven by hair analysis. Despite cessation of exposure to cocaine and aggressive immunosuppressive therapy, the patient remained in a minimally conscious state until death. DISCUSSION: Susac syndrome is a rare entity, and its etiology is not yet fully elucidated. The toxic etiologies have been poorly investigated to date. Further observations are required to determine if cocaine and/or adulterants might play a significant role. PMID- 25142039 TI - Prevention of post-mastectomy neuropathic pain with memantine: study protocol for a randomized controlled trial. AB - BACKGROUND: N-methyl-D-aspartate receptor antagonists are potential therapies for neuropathic pain, and memantine has a good tolerance profile. A preclinical study recently reported that presurgery memantine may prevent neuropathic pain development and cognition dysfunction. Considering the high prevalence of breast cancer and of post-mastectomy neuropathic pain, a clinical trial is carried out to evaluate if memantine may prevent neuropathic pain development and maintain cognitive function and quality of life in cancer patients. METHODS/DESIGN: A randomized clinical trial (NCT01536314) includes 40 women with breast cancer undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) is administered for 4 weeks starting 2 weeks before surgery. Intensity of pain, cognitive function, quality of life and of sleep, anxiety and depression are evaluated with questionnaires. The primary endpoint is pain intensity on a 0 to 10) numerical scale at 3 months post-mastectomy. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at alpha = 0.05. DISCUSSION: The hypothesis of this translational approach is to confirm in patients the beneficial prophylactic effect of memantine observed in animals. Such a protective action of memantine against neuropathic pain and cognitive dysfunction would greatly improve the quality of life of cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01536314 on 16 February 2012. PMID- 25142040 TI - The effect of different concentrations of linseed oil or fish oil in the maternal diet on the fatty acid composition and oxidative status of sows and piglets. AB - N-3 polyunsaturated fatty acids (PUFA) are essential for foetal development. Hence, including n-3 PUFA in the sow diet can be beneficial for reproduction. Both the amount and form (precursor fatty acids vs. long chain PUFA) of supplementation are important in this respect. Furthermore, including n-3 PUFA in the diet can have negative effects, such as decreased arachidonic acid (ARA) concentration and increased oxidative stress. This study aimed to compare the efficacy to increase eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations in the piglet, when different concentrations of linseed oil (LO, source of precursor alpha-linolenic acid) or fish oil (FO, source of EPA and DHA) were included in the maternal diet. Sows were fed a palm oil diet or a diet including 0.5% or 2% LO or FO from day 45 of gestation until weaning. Linoleic acid (LA) was kept constant in the diets to prevent a decrease in ARA, and all diets were supplemented with alpha-tocopherol acetate (150 mg/kg) and organic selenium (0.4 mg/kg) to prevent oxidative stress. Feeding 0.5% LO or 0.5% FO to the sows resulted in comparable EPA concentrations in the 5-day old piglet liver, but both diets resulted in lower EPA concentrations than when 2% LO was fed. The highest EPA concentration was obtained when 2% FO was fed. The DHA level in the piglet liver could only be increased when FO, but not LO, was fed to the sows. The 2% FO diet had no advantage over the 0.5% FO diet to increase DHA in the piglet. Despite the constant LA concentration in the sow diet, a decrease in ARA could not be avoided when LO or FO were included in the diet. Feeding 2% FO to the sows increased the malondialdehyde concentration (marker for lipid peroxidation) in sow plasma, but not in piglets. PMID- 25142042 TI - See hear: psychological effects of music and music-video during treadmill running. AB - BACKGROUND: There is a paucity of work addressing the distractive, affect enhancing, and motivational influences of music and video in combination during exercise. PURPOSE: We examined the effects of music and music-and-video on a range of psychological and psychophysical variables during treadmill running at intensities above and below ventilatory threshold (VT). METHODS: Participants (N = 24) exercised at 10 % of maximal capacity below VT and 10 % above under music only, music-and-video, and control conditions. RESULTS: There was a condition * intensity * time interaction for perceived activation and state motivation, and an intensity * time interaction for state attention, perceived exertion (RPE), and affective valence. The music-and-video condition elicited the highest levels of dissociation, lowest RPE, and most positive affective responses regardless of exercise intensity. CONCLUSIONS: Attentional manipulations influence psychological and psychophysical variables at exercise intensities above and below VT, and this effect is enhanced by the combined presentation of auditory and visual stimuli. PMID- 25142041 TI - PortionControl@HOME: results of a randomized controlled trial evaluating the effect of a multi-component portion size intervention on portion control behavior and body mass index. AB - BACKGROUND: Food portion sizes influence energy intake. PURPOSE: The purpose of this paper is to determine effectiveness of the "PortionControl@HOME" intervention on body mass index and portion control behavior. METHODS: A randomized controlled trial among 278 overweight and obese participants was conducted. PortionControl@HOME aimed to increase: portion size awareness, portion control behavior, portion control cooking skills, and to create a home environment favoring portion control. RESULTS: Intention-to-treat multi-level regression analysis indicated statistically significant effects of the intervention on portion control behavior at 3, 6, and 12 months follow-up. The effect on body mass index was significant only at 3 months follow-up and when outliers (n = 3) were excluded (B = -0.45; 95%CI = -0.88 to -0.04). The intervention effect on body mass index was mediated by portion control behavior. CONCLUSIONS: The intervention improves portion control behavior, which in turn influence body mass index. Once the intervention ceased, sustained effects on body mass index were no longer evident. (Current-Controlled-Trials ISRCTN12363482). PMID- 25142043 TI - [Apocrine poroma. A relatively little known skin tumor with multilineage differentiation]. AB - Poromas were originally classified as eccrine tumors which predominantly consist of poroid ductal cells and differentiate in the direction of sweat gland ducts. However, there have now been many reports on poromas with additional differential characteristics differentiating in the direction of sebaceous and/or apocrine glands and/or hair follicles. These tumors have been termed apocrine poromas. Multilineage differentiation within a poroma can be explained by the embryological association of the sweat duct with the so-called folliculo sebaceous-apocrine unit. The clinical and histopathological features of apocrine poromas are reviewed in comparison to classical eccrine poromas by taking into account seven own cases of apocrine poroma and a review of the literature. It is important for histopathologists not to confuse apocrine poroma with other tumors with multilineage differentiation. Apocrine poroma needs to be distinguished from sebaceoma and from basal cell carcinoma with sebaceous differentiation, in particular, because these tumors have therapeutic consequences for the patient. The main histopathological differences between apocrine poroma, sebaceoma and basal cell carcinoma with sebaceous differentiation are explained. PMID- 25142045 TI - Traits and phylogenetic history contribute to network structure across Canadian plant-pollinator communities. AB - Interaction webs, or networks, define how the members of two or more trophic levels interact. However, the traits that mediate network structure have not been widely investigated. Generally, the mechanism that determines plant-pollinator partnerships is thought to involve the matching of a suite of species traits (such as abundance, phenology, morphology) between trophic levels. These traits are often unknown or hard to measure, but may reflect phylogenetic history. We asked whether morphological traits or phylogenetic history were more important in mediating network structure in mutualistic plant-pollinator interaction networks from Western Canada. At the plant species level, sexual system, growth form, and flower symmetry were the most important traits. For example species with radially symmetrical flowers had more connections within their modules (a subset of species that interact more among one another than outside of the module) than species with bilaterally symmetrical flowers. At the pollinator species level, social species had more connections within and among modules. In addition, larger pollinators tended to be more specialized. As traits mediate interactions and have a phylogenetic signal, we found that phylogenetically close species tend to interact with a similar set of species. At the network level, patterns were weak, but we found increasing functional trait and phylogenetic diversity of plants associated with increased weighted nestedness. These results provide evidence that both specific traits and phylogenetic history can contribute to the nature of mutualistic interactions within networks, but they explain less variation between networks. PMID- 25142046 TI - Yolk carotenoids increase fledging success in great tit nestlings. AB - Avian mothers can influence offspring phenotype through the deposition of different compounds into eggs, such as antibodies, hormones and antioxidants. The concentration of carotenoids in yolk is larger than in maternal plasma, suggesting an important role of these compounds for offspring development. Since carotenoids have to be acquired from the diet, they may be available in limiting amounts to the mothers. Here, we investigated the role of egg carotenoids for offspring growth by experimentally increasing the concentration of yolk lutein, the main carotenoid in great tit (Parus major) yolk. We subsequently measured body condition, oxidative stress, immune response, plumage colouration and fledging success. Lutein increased body mass soon after hatching and fledging success, but did not affect tarsus length, oxidative stress, immune response and plumage colouration. The higher content of yolk lutein could have increased body mass by reducing oxidative stress caused by high metabolic rates of rapidly growing embryos or by promoting cell differentiation and proliferation. The positive effect of lutein on fledging success seems to be mediated by its influence on body mass 3 days post-hatch, since these two traits were correlated. The finding that our treatment did not affect traits measured later in the nestling period, except for fledging success, suggests that yolk lutein has short term effects that are essential to increase survival until fledging. Our study shows the positive effect of yolk lutein on offspring survival in the great tit, and therefore suggests an important role of carotenoid-mediated maternal effects. PMID- 25142048 TI - Anion exchange chromatography for the determination of 5-methyl-2'-deoxycytidine: application to cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. AB - Epigenetic alterations are increasingly implicated in the initiation and progression of cancer. Genome-wide (global) hypomethylation seems to occur in early neoplasia and is a feature of genomic DNA derived from solid tumour tissues like ovarian cancer. Thus, analytical methods that provide sensitive and quantitative information about cytosine methylation in DNA are currently required. In this work, we compare two different anion-exchange columns for the separation of methylated cytosine from the other DNA nucleotides: a silica-based (Tracer Extrasil SAX) column and a polystyrene/divinyl benzene-based (Mono-QTM) column. Under the optimised conditions, linearity range, precision and detection limits of the developed high-performance liquid chromatography (HPLC) method were evaluated and compared using conventional ultraviolet (UV) absorbance detection at 270 nm. Good separation of the five target nucleotides, including 5-methyl-2' deoxycytidine monophosphate (5mdCMP) and 2'-deoxycytidine monophosphate (dCMP) was achieved on the Mono-QTM column with a gradient elution of ammonium acetate buffer (1 M, pH 6.9) at a flow rate of 1 mL min(-1). The coupling of this column to inductively coupled plasma mass spectrometry (ICP-MS) permitted also phosphorous ((31)P) specific detection of the nucleotides. Both detection systems offered adequate analytical performance characteristics, with detection limits of 30 and 40 MUg L(-1) for 5mdCMP by HPLC-UV and HPLC-ICP-MS, respectively. However, the latter method allowed the determination of the global DNA methylation level (%) without the need for external calibration. Different genomic DNA samples were analysed including calf thymus DNA and DNA from two human cancer cell lines (adenocarcinoma epithelial A549 and ovarian carcinoma A2780) using the proposed strategy. In the line A2780, the cisplatin-sensitive and cisplatin-resistant variants were analysed, finding no significant differences in the methylation percentage after treatment with cisplatin. PMID- 25142049 TI - Determination of aromatic amines in human urine using comprehensive multi dimensional gas chromatography mass spectrometry (GCxGC-qMS). AB - Aromatic amines are an important class of harmful components of cigarette smoke. Nevertheless, only few of them have been reported to occur in urine, which raises questions on the fate of these compounds in the human body. Here we report on the results of a new analytical method, in situ derivatization solid phase microextraction (SPME) multi-dimensional gas chromatography mass spectrometry (GCxGC-qMS), that allows for a comprehensive fingerprint analysis of the substance class in complex matrices. Due to the high polarity of amino compounds, the complex urine matrix and prevalence of conjugated anilines, pretreatment steps such as acidic hydrolysis, liquid-liquid extraction (LLE), and derivatization of amines to their corresponding aromatic iodine compounds are necessary. Prior to detection, the derivatives were enriched by headspace SPME with the extraction efficiency of the SPME fiber ranging between 65 % and 85 %. The measurements were carried out in full scan mode with conservatively estimated limits of detection (LOD) in the range of several ng/L and relative standard deviation (RSD) less than 20 %. More than 150 aromatic amines have been identified in the urine of a smoking person, including alkylated and halogenated amines as well as substituted naphthylamines. Also in the urine of a non-smoker, a number of aromatic amines have been identified, which suggests that the detection of biomarkers in urine samples using a more comprehensive analysis as detailed in this report may be essential to complement the approach of the use of classic biomarkers. PMID- 25142050 TI - Anticholinergic medications: an additional contributor to cognitive impairment in the heart failure population? AB - BACKGROUND/OBJECTIVES: Patients with congestive heart failure (CHF) have a high prevalence of cognitive impairment and the association is multifactorial. In general, the burden of anticholinergic drugs has consistently been shown to be a risk factor for cognitive impairment in the elderly. The aim of this study was to assess the cognitive burden of medications in patients with CHF. DESIGN: This was a cross-sectional, retrospective, single-center study. SETTING: The study was conducted in an outpatient setting. PARTICIPANTS: Patients who presented to a comprehensive heart failure clinic during a 1-month period were included. MEASUREMENTS: The primary outcomes of interest were mean anticholinergic cognitive burden (ACB) score of all medications and CHF medications (ACB-CHF), calculated based on the ACB Scoring Scale (ACB-SS). The ACB-CHF score was further dichotomized as 0 or 1 (low anticholinergic burden) versus 2 or 3 (high anticholinergic burden). RESULTS: A total of 182 patients were included. The mean ACB and ACB-CHF scores were 2.4 (range 0-13) and 1.0 (range 0-4), respectively, while 25.8 % of patients had an ACB-CHF score of 2 or 3. There was no association found between ejection fraction in patients with systolic heart failure and the ACB (p = 0.28) or ACB-CHF (p = 0.62) score. CONCLUSION: We conclude that patients with CHF have a substantial exposure to anticholinergic medications with adverse cognitive effects. This may be another important contributor to the increased prevalence of cognitive impairment in these patients. PMID- 25142051 TI - Role of CpG deserts in the epigenetic transgenerational inheritance of differential DNA methylation regions. AB - BACKGROUND: Previously a variety of environmental toxicants were found to promote the epigenetic transgenerational inheritance of disease through differential DNA methylation regions (DMRs), termed epimutations, present in sperm. The transgenerational epimutations in sperm and somatic cells identified in a number of previous studies were further investigated. RESULTS: The epimutations from six different environmental exposures were found to be predominantly exposure specific with negligible overlap. The current report describes a major genomic feature of all the unique epimutations identified (535) as a very low (<10 CpG/100 bp) CpG density in sperm and somatic cells associated with transgenerational disease. The genomic locations of these epimutations were found to contain DMRs with small clusters of CpG within a general region of very low density CpG. The potential role of these epimutations on gene expression is suggested to be important. CONCLUSIONS: Observations suggest a potential regulatory role for lower density CpG regions termed "CpG deserts". The potential evolutionary origins of these regions is also discussed. PMID- 25142052 TI - Development and psychometric testing of the Chinese Postnatal Risk Factors Questionnaire (CPRFQ) for postpartum depression. AB - This article describes the development and psychometric assessment of the Chinese Postnatal Risk Factors Questionnaire (CPRFQ). There were four phases in this process: (1) the items were generated using a literature review and a focus group, (2) content validity was evaluated by an expert panel, (3) a pilot study was conducted with 45 postpartum women to refine the scale, and (4) a convenience sample of 256 postpartum women in China was recruited to complete the questionnaire. Construct validity was established by exploratory factor analysis; a four-factor structure of the scale was accepted (social and family, personality and relationship, mother and infant, maternal feelings and 'doing the month'). These factors explained 47.46 % of the variance. Pearson's correlation coefficient was conducted to test convergent validity with the Edinburgh Postnatal Depression Scale (EPDS) (r = 0.54; p < 0.001). The Cronbach's alpha coefficient of the four subscales ranged from 0.58 to 0.71. The final 18-item version of the questionnaire is potentially a valuable tool for assessing postnatal risk factors in Chinese postpartum mothers. PMID- 25142053 TI - Dynamics of a thin liquid film interacting with an oscillating nano-probe. AB - The dynamic interaction between a local probe and a viscous liquid film, which provokes the deformation of the latter, has been studied. The pressure difference across the air-liquid interface is calculated with a modified Young-Laplace equation, which takes into account the effects of gravity, surface tension, and liquid film-substrate and probe-liquid attractive interaction potentials. This pressure difference is injected into the lubrication approximation equation, in order to depict the evolution of a viscous thin-film. Additionally, a simple periodic function is added to an average separation distance, in order to define the probe motion. The aforementioned coupled equations, which describe the liquid film dynamics, were analysed and numerically solved. The liquid surface undergoes a periodic motion: the approaching probe provides an input energy to the film, which is stored by the latter by increasing its surface deformation; afterwards, when the probe moves away, an energy dissipation process occurs as the surface attempts to recover its original flat shape. Asymptotic regimes of the film surface oscillation are discerned, for extreme probe oscillation frequencies, and several length, wavenumber and time scales are yielded from our analysis, which is based on the Hankel transform. For a given probe-liquid-substrate system, with well-known physical and geometric parameters, a periodic stationary regime and instantaneous and delayed probe wetting events are discerned from the numerical results, depending on the combination of oscillation parameters. Our results provide an interpretation of the probe-liquid film coupling phenomenon, which occurs whenever an AFM test is performed over a liquid sample. PMID- 25142054 TI - Environmental and genetic effects on weight and visual score traits at postweaning in Suffolk sheep. AB - This study aimed to investigate the following environmental effects in Suffolk lambing: contemporary groups, type of birth, and age of animal and age of dam at lambing on conformation (C), precocity (P), musculature (M), and body weight at postweaning (W), and the heritability coefficients and genetic correlations among these traits. Contemporary groups, type of birth, and age of animal and age of dam at lambing were significant for W. For C, all the effects studied were significant, except linear and quadratic effects of age of the animal. For P, all effects studied were significant, except the quadratic effect of age of the animal. For M, the effects of contemporary group, type of birth, and the linear effect of the age of the animal were significant. Heritability estimates were 0.07 +/- 0.03, 0.14 +/- 0.03, 0.09 +/- 0.03, and 0.11 +/- 0.03 for C, P, M, and W, respectively, indicating a positive low response for direct selection. Estimates of genetic correlations among the visual scores (C, P, and M) and W were moderate to highly favorable and positive, ranging from 0.48 to 0.90. These results indicate that selection for visual scores will increase body weight. PMID- 25142055 TI - New insights on obstructive sleep apnea syndrome and related comorbidities in morbidly obese patients submitted to bariatric surgery. PMID- 25142056 TI - Modeling of delays in PKPD: classical approaches and a tutorial for delay differential equations. AB - In pharmacokinetics/pharmacodynamics (PKPD) the measured response is often delayed relative to drug administration, individuals in a population have a certain lifespan until they maturate or the change of biomarkers does not immediately affects the primary endpoint. The classical approach in PKPD is to apply transit compartment models (TCM) based on ordinary differential equations to handle such delays. However, an alternative approach to deal with delays are delay differential equations (DDE). DDEs feature additional flexibility and properties, realize more complex dynamics and can complementary be used together with TCMs. We introduce several delay based PKPD models and investigate mathematical properties of general DDE based models, which serve as subunits in order to build larger PKPD models. Finally, we review current PKPD software with respect to the implementation of DDEs for PKPD analysis. PMID- 25142058 TI - Activation of endothelial transient receptor potential C3 channel is required for small conductance calcium-activated potassium channel activation and sustained endothelial hyperpolarization and vasodilation of cerebral artery. AB - BACKGROUND: Transient receptor potential C3 (TRPC3) has been demonstrated to be involved in the regulation of vascular tone through endothelial cell (EC) hyperpolarization and endothelium-dependent hyperpolarization-mediated vasodilation. However, the mechanism by which TRPC3 regulates these processes remains unresolved. We tested the hypothesis that endothelial receptor stimulation triggers rapid TRPC3 trafficking to the plasma membrane, where it provides the source of Ca(2+) influx for small conductance calcium-activated K(+) (SKCa) channel activation and sustained EC hyperpolarization. METHODS AND RESULTS: Pressurized artery studies were performed with isolated mouse posterior cerebral artery. Treatment with a selective TRPC3 blocker (Pyr3) produced significant attenuation of endothelium-dependent hyperpolarization-mediated vasodilation and endothelial Ca(2+) response (EC-specific Ca(2+) biosensor) to intraluminal ATP. Pyr3 treatment also resulted in a reduced ATP-stimulated global Ca(2+) and Ca(2+) influx in primary cultures of cerebral endothelial cells. Patch clamp studies with freshly isolated cerebral ECs demonstrated 2 components of EC hyperpolarization and K(+) current activation in response to ATP. The early phase was dependent on intermediate conductance calcium-activated K(+) channel activation, whereas the later sustained phase relied on SKC a channel activation. The SKC a channel-dependent phase was completely blocked with TRPC3 channel inhibition or in ECs of TRPC3 knockout mice and correlated with increased trafficking of TRPC3 (but not SKC a channel) to the plasma membrane. CONCLUSIONS: We propose that TRPC3 dynamically regulates SKC a channel activation through receptor-dependent trafficking to the plasma membrane, where it provides the source of Ca(2+) influx for sustained SKC a channel activation, EC hyperpolarization, and endothelium-dependent hyperpolarization-mediated vasodilation. PMID- 25142057 TI - Obesity, physical activity, and their interaction in incident atrial fibrillation in postmenopausal women. AB - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased risk of stroke and death. Obesity is an independent risk factor for AF, but modifiers of this risk are not well known. We studied the roles of obesity, physical activity, and their interaction in conferring risk of incident AF. METHODS AND RESULTS: The Women's Health Initiative (WHI) Observational Study was a prospective observational study of 93 676 postmenopausal women followed for an average of 11.5 years. Incident AF was identified using WHI-ascertained hospitalization records and diagnostic codes from Medicare claims. A multivariate Cox's hazard regression model adjusted for demographic and clinical risk factors was used to evaluate the interaction between obesity and physical activity and its association with incident AF. After exclusion of women with prevalent AF, incomplete data, or underweight body mass index (BMI), 9792 of the remaining 81 317 women developed AF. Women were, on average, 63.4 years old, 7.8% were African American, and 3.6% were Hispanic. Increased BMI (hazard ratio [HR], 1.12 per 5-kg/m(2) increase; 95% confidence interval [CI], 1.10 to 1.14) and reduced physical activity (>9 vs. 0 metabolic equivalent task hours per week; HR, 0.90; 95% CI, 0.85 to 0.96) were independently associated with higher rates of AF after multivariate adjustment. Higher levels of physical activity reduced the AF risk conferred by obesity (interaction P=0.033). CONCLUSIONS: Greater physical activity is associated with lower rates of incident AF and modifies the association between obesity and incident AF. PMID- 25142059 TI - Socioeconomic status and the incidence of atrial fibrillation in whites and blacks: the Atherosclerosis Risk in Communities (ARIC) study. AB - BACKGROUND: No previous studies have examined the interplay among socioeconomic status, sex, and race with the risk of atrial fibrillation (AF). METHODS AND RESULTS: We prospectively followed 14 352 persons (25% black, 75% white, 55% women, mean age 54 years) who were free of AF and participating in the Atherosclerosis Risk in Communities (ARIC) study. Socioeconomic status was assessed at baseline (1987-1989) through educational level and total family income. Incident AF through 2009 was ascertained from electrocardiograms, hospitalizations, and death certificates. Cox regression was used to estimate hazard ratios and 95% CIs of AF for education and family income. Interactions were tested between socioeconomic status and age, race, or sex. Over a median follow-up of 20.6 years, 1794 AF cases occurred. Lower family income was associated with higher AF risk (hazard ratio 1.45, 95% CI 1.27 to 1.67 in those with income less than $25 000 per year compared with those with $50 000 or more per year). The association between education and AF risk varied by sex (P=0.01), with the lowest education group associated with higher AF risk in women (hazard ratio 1.88, 95% CI 1.55 to 2.28) but not in men (hazard ratio 1.15, 95% CI 0.97 to 1.36) compared with the highest education group. Adjustment for cardiovascular risk factors attenuated the associations. There were no interactions with race or age. Blacks had lower AF risk than whites in all income and education groups. CONCLUSIONS: Lower family income was associated with a higher AF risk overall, whereas the impact of education on AF risk was present only in women. Differences in socioeconomic status do not explain the lower risk of AF in blacks compared with whites. PMID- 25142060 TI - Radial access during percutaneous interventions in patients with acute coronary syndromes: should we routinely monitor radial artery patency by ultrasonography promptly after the procedure and in long-term observation? AB - Access-site vascular complications in patients undergoing transradial coronary procedures are rare but may have relevant clinical consequences. The aim of the study was to evaluate: (1) radial artery's (RA) patency immediately after the procedure and in long-term observation, (2) factors influencing the frequency of radial artery's occlusion (RAO) after percutaneous coronary intervention (PCI) procedures performed via transradial access in the group of 220 patients with acute coronary syndromes (ACS). RA ultrasound was performed 48-72 h after the procedure and in those who were diagnosed with RAO-again after 6-12 months. According to the ultrasonographic findings, the patients were divided into two sub-groups: 187 pts (85 %) with patent RA after PCI and 33 pts (15 %) with RAO. Both sub-groups significantly statistically differed with regard to the frequency of local hematomas-15 versus 27.3 % (p = 0.02), the frequency of applying IIbIIIa inhibitors in PCI-6.4 versus 15.1 % (p = 0.015) and procedure duration-0.59 +/- 0.37 versus 0.77 +/- 0.38 (p = 0.014), respectively. In a multifactorial analysis the only factor influencing RA patency promptly after the procedure was PCI duration (p < 0.05, r = -0.22). In the follow-up, right RA remained still obstructed in 28 patients (12.7 %) whereas in five patients (2.3 %) the regular flow in RA was resumed. The chronic RAO was clinically silent. Due to insignificant frequency of the occurrence of RAO after PCI procedure in patients with ACS as well as practically lack of clinical consequences of this artery's occlusion in long-term observation, we do not see any implications to routine ultrasound periprocedural RA evaluation. PMID- 25142061 TI - Dynamics of anti-human leukocyte antigen antibodies after renal transplantation and their impact on graft outcome. AB - The purpose of this study was to sequentially monitor anti-HLA antibodies and correlate the results with antibody-mediated rejection (AMR), graft survival (GS), and graft function (GF). We collected sera from 111 kidney transplant recipients on transplant days 0, 7, 14, 30, 60, 90, 180, and 360 and analyzed PRA levels by ELISA. DSAs were analyzed by single-antigen beads in rejecting kidneys. At pre-transplant, 79.3% of the patients were non-sensitized (PRA = 0%) and 20.7% were sensitized (PRA > 1%). After transplant, patients were grouped by PRA profile: no anti-HLA antibodies pre- or post-transplant (group HLApre-/post-; n = 80); de novo anti-HLA antibodies post-transplant (group HLApre-/post+; n = 8); sensitized pre-transplant/increased PRA post-transplant (group HLApre+/post?; n = 9); and sensitized pre-transplant/decreased PRA post-transplant (group HLApre+/post?; n = 14). De novo anti-HLA antibodies were detected at 7-180 d. In sensitized patients, PRA levels changed within the first 30 d post-transplant. Incidence of AMR was higher in HLApre-/post+ and HLApre+/post? than in HLApre /post-, and HLApre+/post? (p < 0.001) groups. One-yr death-censored GS was 36% in group HLApre+/post?, compared with 98%, 88% and 100% in groups HLApre-/post-, HLApre-/post+, and HLApre+/post?, respectively (p < 0.001). Excluding first-year graft losses, GF and GS were similar among the groups. In conclusion, post transplant antibody monitoring can identify recipients at higher risk of AMR. PMID- 25142062 TI - Effect of supranutritional organic selenium supplementation on postpartum blood micronutrients, antioxidants, metabolites, and inflammation biomarkers in selenium-replete dairy cows. AB - Dairy cows have increased nutritional requirements for antioxidants postpartum. Supranutritional organic Se supplementation may be beneficial because selenoproteins are involved in regulating oxidative stress and inflammation. Our objective was to determine whether feeding Se-yeast above requirements to Se replete dairy cows during late gestation affects blood micronutrients, antioxidants, metabolites, and inflammation biomarkers postpartum. During the last 8-weeks before calving, dairy cows at a commercial farm were fed either 0 (control) or 105 mg Se-yeast once weekly (supranutritional Se-yeast), in addition to Na selenite at 0.3 mg Se/kg dry matter in their rations. Concentrations of whole-blood (WB) Se and serum Se, erythrocyte glutathione (GSH), and serum albumin, cholesterol, alpha-tocopherol, haptoglobin, serum amyloid A (SAA), calcium, magnesium, phosphorus, non-esterified fatty acids, and beta hydroxybutyrate were measured directly after calving, at 48 h, and 14 days of lactation in 10 cows of each group. Supranutritional Se-yeast supplementation affected indicators of antioxidant status and inflammation. Cows fed a supranutritional Se-yeast supplement during the last 8-weeks of gestation had higher Se concentrations in WB (overall 52 % higher) and serum (overall 36 % higher) at all-time points, had higher SAA concentrations at 48 h (98 % higher), had higher erythrocyte GSH (38 % higher) and serum albumin concentrations (6.6 % higher) at 14 days, and had lower serum cholesterol concentrations and higher alpha-tocopherol/cholesterol ratios at calving and at 48 h compared with control cows. In conclusion, feeding Se-replete cows during late gestation a supranutritional Se-yeast supplement improves antioxidant status and immune responses after calving without negatively impacting other micronutrients and energy status. PMID- 25142063 TI - Lardy brains make Parkinson's disease mice worse. PMID- 25142064 TI - IRBIS: a systematic search for conserved complementarity. AB - IRBIS is a computational pipeline for detecting conserved complementary regions in unaligned orthologous sequences. Unlike other methods, it follows the "first fold-then-align" principle in which all possible combinations of complementary k mers are searched for simultaneous conservation. The novel trimming procedure reduces the size of the search space and improves the performance to the point where large-scale analyses of intra- and intermolecular RNA-RNA interactions become possible. In this article, I provide a rigorous description of the method, benchmarking on simulated and real data, and a set of stringent predictions of intramolecular RNA structure in placental mammals, drosophilids, and nematodes. I discuss two particular cases of long-range RNA structures that are likely to have a causal effect on single- and multiple-exon skipping, one in the mammalian gene Dystonin and the other in the insect gene Ca-alpha1D. In Dystonin, one of the two complementary boxes contains a binding site of Rbfox protein similar to one recently described in Enah gene. I also report that snoRNAs and long noncoding RNAs (lncRNAs) have a high capacity of base-pairing to introns of protein-coding genes, suggesting possible involvement of these transcripts in splicing regulation. I also find that conserved sequences that occur equally likely on both strands of DNA (e.g., transcription factor binding sites) contribute strongly to the false-discovery rate and, therefore, would confound every such analysis. IRBIS is an open-source software that is available at http://genome.crg.es/~dmitri/irbis/. PMID- 25142065 TI - Chloroplast RNA editing going extreme: more than 3400 events of C-to-U editing in the chloroplast transcriptome of the lycophyte Selaginella uncinata. AB - RNA editing in chloroplasts and mitochondria of land plants differs significantly in abundance. For example, some 200-500 sites of cytidine-to-uridine RNA editing exist in flowering plant mitochondria as opposed to only 30-50 such C-to-U editing events in their chloroplasts. In contrast, we predicted significantly more chloroplast RNA editing for the protein-coding genes in the available complete plastome sequences of two species of the spike moss genus Selaginella (Lycopodiophyta). To evaluate these predictions we investigated the Selaginella uncinata chloroplast transcriptome. Our exhaustive cDNA studies identified the extraordinary number of 3415 RNA-editing events, exclusively of the C-to-U type, in the 74 mRNAs encoding intact reading frames in the S. uncinata chloroplast. We find the overwhelming majority (61%) of the 428 silent editing events leaving codon meanings unaltered directly neighboring other editing events, possibly suggesting a sterically more flexible RNA-editing deaminase activity in Selaginella. No evidence of RNA editing was found for tRNAs or rRNAs but we identified a total of 74 editing sites in cDNA sequences of four group II introns (petBi6g2, petDi8g2, ycf3i124g2, and ycf3i354g2) retained in partially matured transcripts, which strongly contribute to improved base-pairing in the intron secondary structures as a likely prerequisite for their splicing. PMID- 25142066 TI - De novo translation initiation on membrane-bound ribosomes as a mechanism for localization of cytosolic protein mRNAs to the endoplasmic reticulum. AB - The specialized protein synthesis functions of the cytosol and endoplasmic reticulum compartments are conferred by the signal recognition particle (SRP) pathway, which directs the cotranslational trafficking of signal sequence encoding mRNAs from the cytosol to the endoplasmic reticulum (ER). Although subcellular mRNA distributions largely mirror the binary pattern predicted by the SRP pathway model, studies in mammalian cells, yeast, and Drosophila have also demonstrated that cytosolic protein-encoding mRNAs are broadly represented on ER bound ribosomes. A mechanism for such noncanonical mRNA localization remains, however, to be identified. Here, we examine the hypothesis that de novo translation initiation on ER-bound ribosomes serves as a mechanism for localizing cytosolic protein-encoding mRNAs to the ER. As a test of this hypothesis, we performed single molecule RNA fluorescence in situ hybridization studies of subcellular mRNA distributions and report that a substantial fraction of mRNAs encoding the cytosolic protein GAPDH resides in close proximity to the ER. Consistent with these data, analyses of subcellular mRNA and ribosome distributions in multiple cell lines demonstrated that cytosolic protein mRNA ribosome distributions were strongly correlated, whereas signal sequence-encoding mRNA-ribosome distributions were divergent. Ribosome footprinting studies of ER bound polysomes revealed a substantial initiation codon read density enrichment for cytosolic protein-encoding mRNAs. We also demonstrate that eukaryotic initiation factor 2alpha is bound to the ER via a salt-sensitive, ribosome independent mechanism. Combined, these data support ER-localized translation initiation as a mechanism for mRNA recruitment to the ER. PMID- 25142067 TI - Palliative treatment for symptomatic malignant pericardial effusion?. AB - Consensus has yet to emerge regarding the optimal choice of therapy in the management of malignant pericardial effusion. We review the literature to evaluate the existing evidence on the clinical effectiveness of surgical and interventional cardiological approaches. A formal literature search for all studies addressing the treatment of pericardial effusion in cancer patients was undertaken using predefined keywords. Abstracts were screened and reviewed, and data extracted. Data on intervention type, number of patients treated, number of patients surviving the procedure, effusion recurrences, need for further interventions and procedure-related complications were obtained from each study and collated in a quantitative synthesis. Of 1181 articles identified, 59 contained sufficient quantitative information to be included in the synthesis. A total of 2322 patients with symptomatic pericardial effusion were identified, of which 1399 patients were reported to have underlying malignancy. Three surgical approaches were described in a total of 19 studies, with overall success rates ranging from 93.3 to 100% and associated complication rates ranging from 4.5 to 10.3%. The remaining 40 studies reported four non-surgical treatment modalities, with success rates of 55.1-90.4% and complication rates of 5.9-32%. Data from the literature suggest that surgical drainage of the pericardium is superior to non surgical approaches for symptom relief, effusion recurrence and morbidity; however, the lack of randomized controlled trials means that selection bias remains an important limitation to the field and definitive adequately controlled trials should be a priority. PMID- 25142068 TI - Prospective, randomized, double-blinded trial of bone marrow cell transplantation combined with coronary surgery - perioperative safety study. AB - OBJECTIVES: We present here a sub-study of our prospective, randomized, double blinded trial of bone marrow mononuclear cell (BMMC) transplantation with coronary artery bypass surgery (CABG) (ClinicalTrials.gov Identifier: NCT00418418), evaluating our secondary end-point concerning hospital stay as well as perioperative morbidity. Injecting a substantial amount of biologically active cells into a diseased myocardium inspires concerns for safety, a concern overlooked in previous trials. METHODS: We evaluated the immediate perioperative effects of intramyocardial injection of autologous BMMCs combined with CABG. In a randomized double-blinded manner, 39 patients received injections either of BMMCs (n = 20) or of vehicle medium (n = 19). The patients' haemodynamics, arterial blood gases, systemic vein oxygen level, blood glucose, acid-base balance, lactate, haemoglobin, body temperature and diuresis, as well as medications needed, were recorded in the operating theatre and in the intensive care unit (ICU) every 4 h throughout the first postoperative 24 h. RESULTS: No dissimilarities in these parameters were detectable. In the ICU, the median need for adrenaline was 0.0086 ug/kg/min (first quartile 0.0000, third quartile 0.0204) for controls and 0.0090 ug/kg/min (0.0000, 0.0353) for BMMC patients (P = 0.757); for noradrenaline, 0.0586 ug/kg/min (0.0180, 0.0888) for controls and 0.0279 ug/kg/min (0.0145, 0.0780) for BMMC patients (P = 0.405). The median stay at the ICU was 2 days for both groups (1, 2 for controls; 1, 3 for BMMCs; P = 0.967). Within the first postoperative day, one control patient had an elevated level of creatine kinase-myocardial band fraction mass (CK-MBm) up to >100 ug/l; no BMMC patient showed elevated CK-MBm levels (P = 0.474). CONCLUSIONS: Both intramyocardial BMMC and placebo injections appear safe during surgery and immediate ICU stay after treatment of heart failure. PMID- 25142069 TI - Controlled lung reperfusion to reduce pulmonary ischaemia/reperfusion injury after cardiopulmonary bypass in a porcine model. AB - OBJECTIVES: Ischaemia/reperfusion (I/R) injury of the lungs contributes to pulmonary dysfunction after cardiac surgery with cardiopulmonary bypass (CPB), leading to increased morbidity and mortality of patients. This study investigated the value of controlled lung reperfusion strategies on lung ischaemia-reperfusion injury in a porcine CPB model. METHODS: Pigs were subjected to routine CPB for 120 min with 60 min of blood cardioplegic cardiac arrest (CCA). Following CCA, the uncontrolled reperfusion (UR, n = 6) group was conventionally weaned from CPB. Two groups underwent controlled lung reperfusion strategies (CR group: controlled reperfusion conditions, n = 6; MR group: controlled reperfusion conditions and modified reperfusate, n = 6) via the pulmonary artery before CPB weaning. Sham-operated pigs (n = 7) served as controls. Animals were followed up until 4 h after CPB. Pulmonary function, haemodynamics, markers of inflammation, endothelial injury and oxidative stress as well as morphological lung alterations were analysed. RESULTS: CPB (UR group) induced deterioration of pulmonary function (lung mechanics, oxygenation index and lung oedema). Also, controlled lung reperfusion groups (CR and MR) presented with pulmonary dysfunction after CPB. However, compared with UR, controlled lung reperfusion strategies (CR and MR) improved lung mechanics and reduced markers of oxidative stress, but without alteration of haemodynamics, oxygenation, inflammation, endothelial injury and lung morphology. Both controlled reperfusion groups were similar without relevant differences. CONCLUSION: Controlled lung reperfusion strategies attenuated a decrease in lung mechanics and an increase in oxidative stress, indicating an influence on CPB-related pulmonary injury. However, they failed to avoid completely CPB-related lung injury, implying the need for additional strategies given the multifactorial pathophysiology of postoperative pulmonary dysfunction. PMID- 25142070 TI - Characteristics of chromium-allergic dermatitis patients prior to regulatory intervention for chromium in leather: a questionnaire study. AB - BACKGROUND: Chromium-tanned leather articles currently constitute the most important cause of contact allergy to chromium in Denmark. A regulation on the content of hexavalent chromium in leather was adopted in November 2013 by the EU member states. OBJECTIVES: To characterize patients with chromium allergy and their disease, to serve as a baseline for future studies on the potential effect of the new regulation on chromium in leather. METHODS: A questionnaire case control study was performed on 155 dermatitis patients with positive patch test reactions to potassium dichromate and a matched control group of 621 dermatitis patients. Comparisons were made by use of a chi(2) -test and the Mann-Whitney U test. Logistic regression analyses were used to test for associations. RESULTS: Sixty-six per cent of chromium-allergic patients had a positive history of contact dermatitis caused by leather exposure. They had a significantly lower quality of life (p < 0.001), a higher prevalence of dermatitis during the last year (p = 0.008), a higher use of medication during the past 12 months (p = 0.001) and a higher prevalence of sick leave (p = 0.007) than patients in the control group. CONCLUSIONS: Chromium-allergic patients have more severe and more chronic contact dermatitis. Their primary chromium exposure comes from leather articles. PMID- 25142071 TI - Arene ruthenium(ii) complex, a potent inhibitor against proliferation, migration and invasion of breast cancer cells, reduces stress fibers, focal adhesions and invadopodia. AB - Effective chemotherapy drugs for cancer that would inhibit tumor growth and suppress metastasis are currently lacking. In this study, a series of arene ruthenium complexes, [(eta6-arene)Ru(H2iip)Cl]Cl (arene = p-cymene, RAWQ03; CH3C6H5, RAWQ04; and C6H6, RAWQ11), were synthesized and their inhibitory activity against tumor cells were evaluated. The results showed that the complex RAWQ11 inhibited the growth of MDA-MB-231 breast cancer cells by inducing S-phase arrest, which is closely related to the inhibition of cell mitosis-mediated cell nucleus damage. Further studies showed that RAWQ11 can inhibit the invasion and metastasis of MDA-MB-231 cells. The morphology of MDA-MB-231 cells changed, the number of focal adhesions decreased, and the stress fibers de-polymerized upon dealing with the complex RAWQ11. The FITC-gelatin assay confirmed that the formation of invadopodia in MDA-MB-231 cells was significantly blocked by RAWQ11. Furthermore, RAWQ11 can block the AKT signal pathway by upregulating the PTEN expression through binding and downregulating miR-21. These results demonstrated that this type of arene ruthenium(ii) complex can block the invadopodia formation by regulating the PTEN/AKT signal pathway mediated by miR-21 to inhibit the invasion and metastasis of breast cancer cells. Therefore, this complex can be used as a potential dual functional agent to inhibit the growth and metastasis of tumor cells. PMID- 25142072 TI - Replication competent virus as an important source of bias in HIV latency models utilizing single round viral constructs. AB - The central memory T cell (TCM) model forms a unique HIV-1 latency model based on primary cells that closely resemble in vivo TCM. The virus employed in this model is based on an engineered vector incapable of replication after initial infection. We show that despite this strategy, replication competent viral particles are released into the culture medium due to recombination between overlapping sequences of the env deleted HIV genome that is co-transfected with intact env. This finding emphasizes the need for careful data analysis and interpretation if similar constructs are employed and urges for additional caution during laboratory work. PMID- 25142073 TI - The prognostic significance of respiratory rate in patients with pneumonia: a retrospective analysis of data from 705,928 hospitalized patients in Germany from 2010-2012. AB - BACKGROUND: Measurement of the respiratory rate is an important instrument for assessing the severity of acute disease. The respiratory rate is often not measured in routine practice because its clinical utility is inadequately appreciated. In Germany, documentation of the respiratory rate is obligatory when a patient with pneumonia is hospitalized. This fact has enabled us to study the prognostic significance of the respiratory rate in reference to a large medical database. METHOD: We retrospectively analyzed data from the external quality assurance program for community-acquired pneumonia for the years 2010-2012. All patients aged 18 years or older who were not mechanically ventilated on admission were included in the analysis. Logistic regression was used to determine the significance of the respiratory rate as a risk factor for in-hospital mortality. RESULTS: 705,928 patients were admitted to the hospital with community-acquired pneumonia (incidence: 3.5 cases per 1000 adults per year). The in-hospital mortality of these patients was 13.1% (92 227 persons). The plot of mortality as a function of respiratory rate on admission was U-shaped and slanted to the right, with the lowest mortality at a respiratory rate of 20/min on admission. If patients with a respiratory rate of 12-20/min are used as a baseline for comparison, patients with a respiratory rate of 27-33/min had an odds ratio (OR) of 1.72 for in-hospital death, and those with a respiratory rate above 33/min had an OR of 2.55. Further independent risk factors for in-hospital death were age, admission from a nursing home, hospital, or rehabilitation facility, chronic bedridden state, disorientation, systolic blood pressure, and pulse pressure. CONCLUSION: Respiratory rate is an independent risk marker for in-hospital mortality in community-acquired pneumonia. It should be measured when patients are admitted to the hospital with pneumonia and other acute conditions. PMID- 25142074 TI - Mistletoe treatment for cancer--promising or passe? PMID- 25142075 TI - Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: a randomized controlled trial. AB - BACKGROUND: The treatment of cancer patients with mistletoe extract is said to prolong their survival and, above all, improve their quality of life. We studied whether the quality of life of patients with advanced pancreatic cancer could be improved by mistletoe extract. METHOD: An open, single-center, group-sequential, randomized phase III trial (ISRCTN70760582) was conducted. From January 2009 to December 2010, 220 patients with locally advanced or metastatic pancreatic cancer who were receiving no further treatment for pancreatic cancer other than best supportive care were included in this trial. They were stratified by prognosis and randomly allocated either to a group that received mistletoe treatment or to one that did not. Mistletoe extract was given in escalating doses by subcutaneous injection three times a week. The planned interim evaluation of data from 220 patients indicated that mistletoe treatment was associated with longer overall survival, and the trial was terminated prematurely. After termination of the study, the results with respect to quality of life (assessed with the QLO-C30 scales of the European Organisation for Research and Treatment of Cancer) and trends in body weight were evaluated. RESULTS: Data on quality of life and body weight were obtained from 96 patients treated with mistletoe and 72 control patients. Those treated with mistletoe did better on all 6 functional scales and on 7 of 9 symptom scales, including pain (95% confidence interval [CI] -29 to 17), fatigue (95% CI -36.1 to -25.0), appetite loss (95% CI -51 to -36.7), and insomnia (95% CI -45.8 to -28.6). This is reflected by the trend in body weight during the trial. CONCLUSION: In patients with locally advanced or metastatic pancreatic carcinoma, mistletoe treatment significantly improves the quality of life in comparison to best supportive care alone. Mistletoe is an effective second-line treatment for this disease. PMID- 25142076 TI - The diagnosis and graded therapy of atopic dermatitis. AB - BACKGROUND: Atopic dermatitis is the most common skin disease in children, with a prevalence of 10% to 15%, and is common in adults as well. Close coordination between primary care physicians and specialists is essential for the adequate treatment of chronically and severely affected patients. METHOD: This article is a review of pertinent publications that were retrieved by a selective search in Pubmed, with additional consideration of the guidelines of the Association of Medical Scientific Societies in Germany (AWMF) and the European Dermatology Forum. RESULTS: Trigger factors such as skin irritants, allergens, microbial pathogens, and psychological factors can affect the condition of the skin differently in individual patients and should be individually assessed. The use of skin moisturising creams or emollients along with avoidance of specific and unspecific irritants is of great importance, as these patients have an impaired cutaneous barrier. Topical anti-inflammatory treatment with glucocorticoids or calcineurin inhibitors is a central part of the management of atopic dermatitis; in exceptional cases, severely affected patients are treated with systemic anti inflammatory drugs. Interdisciplinary patient education has been found to be an effective tool in the complex management of this disease. Chronically and severely affected patients present special challenges for diagnosis and treatment. CONCLUSION: Recent advances in the understanding of the molecular basis of cutaneous barrier disorders and of congenital and acquired immune disorders have led to new approaches to the treatment of atopic dermatitis. PMID- 25142077 TI - Improving the sensory and oxidative stability of cooked and chill-stored lamb using dietary rosemary diterpenes. AB - Two dietary rosemary extracts (DREs) containing diterpenes (carnosic acid and carnosol at 1:1 and 2:1 w:w) were tested in fattening lambs to stabilize the sensory quality of cooked and chill-stored patties. A total of 63 lambs were fed freely for 80 +/- 5 d with a basal diet supplemented or not with DRE. Minced leg meat from each lamb was used to make patty batches. The patties were cooked at 72 oC for 2 min, aerobically packed, kept at 2 oC for up to 4 d and then reheated. Sensory traits (color, odor, flavor, and texture), CIELab color, and lipid oxidation (assessed as TBARS) were determined. In a first experiment, the lamb diet was supplemented with 600 mg of 1:1-DRE or 2:1-DRE kg(-1) feed. The 1:1-DRE diet delayed discoloration, flavor deterioration, and rancidity, while the 2:1 DRE diet was ineffective in this respect. In a second experiment, 4 supplementation levels of 1:1-DRE (0, 200, 400, and 600 mg kg(-1) feed) were compared. Flavor deterioration was delayed when the lamb diet was supplemented with at least 400 mg 1:1-DRE kg(-1) feed. The effects of the diet on the odor, flavor, and color were corroborated by differences in TBARS and CIELab. The results obtained suggest that rosemary diterpenes and/or their active secondary compounds deposited in muscle can act as endogenous antioxidants in cooked lamb. The carnosol intake seems crucial in the antioxidant actions achieved through DRE. The use of rosemary antioxidants in animal feeding would allow meat-based dishes to be preserved longer without adding preservatives. PMID- 25142078 TI - Upper airway collapse during drug induced sleep endoscopy: head rotation in supine position compared with lateral head and trunk position. AB - Drug induced sedated sleep endoscopy (DISE) is often employed to determine the site, severity and pattern of obstruction in patients with sleep apnea. DISE is usually performed in supine position. We recently showed that the obstruction pattern is different when DISE is performed in lateral position. In this study, we compared the outcomes of DISE performed in supine position with head rotated, with the outcomes of DISE performed with head and trunk in lateral position. The Prospective study design was used in the present study. Sixty patients with OSA (44 male; mean apnea hypopnea index (AHI) 20.8 +/- 17.5 events/h) underwent DISE under propofol sedation. Patients were placed in lateral position, and the upper airway collapse was evaluated. The patients were then placed in supine position with the head rotated to the right side. DISE outcomes were scored using the VOTE classification system. In lateral position, nine patients (15.0%) had a complete antero-posterior (A-P) collapse at the level of the velum, nine had a partial A-P collapse. During head rotation and trunk in supine position, at the level of the velum, four patients (6.7%) had a complete A-P collapse, while two patients (3.3%) had a partial A-P collapse. For all other sites, the patterns of collapse were not significantly different between head rotation and lateral position. During DISE, rotation of the head in supine position, and lateral head and trunk position present similar sites, severity and patterns of upper airway collapse, with the exception of collapse at the level of the velum. Here the severity of A P collapse is less severe during head rotation than in lateral head and trunk position. PMID- 25142079 TI - Attempt to improve functional outcomes in supracricoid laryngectomy in T2b and T3 glottic cancers. AB - The goal of this study was to compare the survival rate and functional outcome of an open partial horizontal laryngectomies, Type IIa and modified Type IIa (OPHL Type IIa and OPHL mType IIa), in treatment of moderately advanced glottic carcinoma. Retrospective analysis. 80 Patients underwent OPHL Type IIa and 27, OPHL modified Type IIa (OPHL mType IIa) between the years 2001 and 2009. Clinical staging was performed according to the UICC criteria (2002). Primary endpoints of study were recurrence rate, and 3- and 5-year survival time. Secondary endpoints were laryngeal functions: respiration, swallowing and voice. There were no significant differences within local and regional recurrence rates, organ preservation rate, 3- and 5-year specific disease survival rates between OPHL Type II and OPHL modified Type IIa. Significantly lower need for temporary (OPHL mType IIa 4/27, OPHL Type IIa 30/80) and permanent tracheostomy (OPHL mType IIa 2/27, OPHL Type IIa 16/80) was found. All but one patient (OPHL Type IIa) achieved unrestricted diet. Significantly differed social eating, this ability gained 25/27 OPHL mType IIa and 54/80 OPHL Type IIa (p < 0.05). Voice handicap index revealed a decrease in quality of life in all areas; OPHL Type IIa and OPHL mType IIa differed significantly (31 and 46 points respectively, p < 0.005). The MPT value (longest pitch) for OPHL Type IIa and OPHL mType IIa lasted 8 s and 10, respectively (p < 0.005). There was no significant difference in oncological outcomes between the two types of OPHL succeeded in the earlier extubation, thus significantly lowering the need for temporary and permanent tracheotomy and providing better long-term swallowing. Although the voice was altered in all observed OPHL patients, modified Type IIa technique proved to be superior to the Type IIa in terms of voice quality. Thus, OPHL modified Type IIa is worth promoting, as long as indications were strictly conformed. PMID- 25142080 TI - Single-incision transaxillary robotic total thyroidectomy for Graves' disease: improved feasibility and safety with novel robotic instrumentation. AB - BACKGROUND: Graves' disease represents a relative contraindication for robotic thyroidectomy due to increased vascularity with a higher risk of intraoperative bleeding. With a novel robotic instrumentation, however, it is possible to reduce this risk considerably. METHODS: A 30-year-old female patient with Graves' disease and keloid-prone olive skin underwent a single-incision transaxillary robotic total thyroidectomy through the left axilla using an 8-mm Fenestrated bipolar forceps instead of the standard 8-mm ProGrasp forceps. RESULTS: Total blood loss was 25 ml, and robotic console time was 132 min. There was no postoperative recurrent palsy. Postoperative parathormone level was 47 ng/l (preop.: 56 ng/l), and serum calcium level was normal at 2,17 mmol/l (preop.: 2,23 mmol/l). CONCLUSION: Transaxillary robotic surgery (TARS) with unilateral single-incision access is feasible and safe for Graves' disease with minimal blood loss and reduced risk of conversion thanks to the bipolar capability of the 8-mm Fenestrated bipolar forceps. PMID- 25142081 TI - How often parapharyngeal space is encountered in TORS oropharynx cancer resection. AB - Early stage oropharyngeal squamous cell carcinoma (OPSCC) may occasionally invade parapharyngeal space (PPS). Tumor invasion of PPS structures such as the carotid artery, internal jugular vein and cranial nerves IX-XII may add significant morbidity. We analyzed 73 patients who underwent transoral robotic surgery (TORS) for OPSCC between 2008 and 2012. Patients were selected based on preoperative evaluation including detailed physical and endoscopic examination, neck CT and/or PET-CT scan. T1, T2 and selected T3 cases were included in this study. None of the patients had obvious PPS extension on preoperative evaluation. All patients had OPSCC in palatine tonsil (60; 82.2 %) and base of tongue (13; 17.8 %). Twenty seven patients had cT1 (37 %), 39 had cT2 (53.4 %), and 7 had cT3 (9.6 %) disease in clinical and radiologic evaluation. None of the oropharyngeal lesions had obvious radiologic PPS extension prior to operation. During TORS procedure, we encountered PPS in 18 (24.6 %) patients while resecting the deep margin. These parapharynx resections involved external carotid artery in 1, medial pterygoid muscle in 2, and parapharyngeal fat with or without styloid musculature in the remaining 15 patients. Except three cases, we were able to remove the lesions en bloc with negative surgical margins. TORS resection of oropharyngeal cancer extending to PPS appears to be a safe and feasible technique with minimal complications. Significant experience with TORS and further understanding of the endoscopic anatomy of PPS could obviate the morbidity associated with tumor resection in this dense neurovascular region. PMID- 25142083 TI - The ratios of urinary beta2-microglobulin and NAG to creatinine vary with age in children. AB - BACKGROUND: Although urinary biochemical markers can be assessed by their ratio to urinary creatinine (U-Cr) concentration, reference values in adults may not be applicable to children because the amount of Cr excreted varies by body size. We therefore measured the relationship between age and the ratios of urinary beta-2 microglobulin (U-beta2MG), N-acetyl-beta-d-glucosaminidase (U-NAG), calcium (U Ca) and protein (U-Pr) concentration to those of U-Cr in children. METHODS: Fifty seven patients aged >1 year with benign familial hematuria (median age, 6.3 years) were divided into three age groups: 1-4, 5-9, and >=10 years. Urinary biomarkers were assayed using actual values; ratios to actual U-Cr values; and our standardized metric, namely 100-fold the ratio of serum Cr to U-Cr concentration; and the relationship of each of these to age was determined. RESULTS: The ratios of U-beta2MG, U-NAG and U-Ca to Cr varied significantly by age, being higher in younger than in older children, but the actual and standardized values of each did not vary by age, nor did any measurement of U-Pr. CONCLUSIONS: The ratios of urinary markers of tubular function, including U beta2MG, U-NAG and U-Ca, to Cr vary by age, being higher in younger children. In contrast, the ratios of urinary markers of glomerular filtration (such as U-Pr)to Cr do not vary by age, making them suitable for corrections relative to Cr. PMID- 25142082 TI - Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route. AB - Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID- 25142084 TI - Advancing groundwater technology on the Prairie. PMID- 25142085 TI - Randomised trial of no hydration vs. sodium bicarbonate hydration in patients with chronic kidney disease undergoing acute computed tomography-pulmonary angiography. AB - BACKGROUND: Hydration to prevent contrast-induced acute kidney injury (CI-AKI) induces a diagnostic delay when performing computed tomography-pulmonary angiography (CTPA) in patients suspected of having acute pulmonary embolism. AIM: To analyze whether withholding hydration is non-inferior to sodium bicarbonate hydration before CTPA in patients with chronic kidney disease (CKD). METHODS: We performed an open-label multicenter randomized trial between 2009 and 2013. One hundred thirty-nine CKD patients were randomized, of whom 138 were included in the intention-to-treat population: 67 were randomized to withholding hydration and 71 were randomized to 1-h 250 mL 1.4% sodium bicarbonate hydration before CTPA. Primary outcome was the increase in serum creatinine 48-96 h after CTPA. Secondary outcomes were the incidence of CI-AKI (creatinine increase > 25%/> 0.5 mg dL(-1) ), recovery of renal function, and the need for dialysis within 2 months after CTPA. Withholding hydration was considered non-inferior if the mean relative creatinine increase was <= 15% compared with sodium bicarbonate. RESULTS: Mean relative creatinine increase was -0.14% (interquartile range -15.1% to 12.0%) for withholding hydration and -0.32% (interquartile range -9.7% to 10.1%) for sodium bicarbonate (mean difference 0.19%, 95% confidence interval 5.88% to 6.25%, P-value non-inferiority < 0.001). CI-AKI occurred in 11 patients (8.1%): 6 (9.2%) were randomized to withholding hydration and 5 (7.1%) to sodium bicarbonate (relative risk 1.29, 95% confidence interval 0.41-4.03). Renal function recovered in 80.0% of CI-AKI patients within each group (relative risk 1.00, 95% confidence interval 0.54-1.86). None of the CI-AKI patients developed a need for dialysis. CONCLUSION: Our results suggest that preventive hydration could be safely withheld in CKD patients undergoing CTPA for suspected acute pulmonary embolism. This will facilitate management of these patients and prevents delay in diagnosis as well as unnecessary start of anticoagulant treatment while receiving volume expansion. PMID- 25142086 TI - Computational evaluation of tris(carbene)borate donor properties in {NiNO}(10) complexes. AB - Electronic structure calculations are performed to characterise the structures, energies, and spectroscopic data for a series of four-coordinate tris(carbene)borate {NiNO}(10) complexes. There is excellent agreement between the computational and experimental results for known complexes, allowing for structure-function relationships to be delineated. Calculations that provide insights into the synthetic accessibility of nickel(iv) nitrides by oxygen atom abstraction from these complexes are also reported. PMID- 25142087 TI - Using miglitol at 30 min before meal is effective in hyperinsulinemic hypoglycemia after a total gastrectomy. AB - A 45-year-old woman who had undergone total gastrectomy for gastric cancer presented with a history of postprandial hypoglycemic episodes with loss of consciousness after meals. Laboratory findings revealed marked hyperinsulinemia and hypoglycemia after a meal. We first treated the patient with octreotide; however, she was unable to continue the treatment because of adverse effects of the drug, such as nausea and headache. Diazoxide was used next for preventing hyperinsulinemia; however, this was not effective for suppressing the postprandial insulin secretion. Since hypoglycemia following gastrectomy is thought to be caused by rapid delivery of nutrients into the duodenum, we performed a meal tolerance test while varying the timing of administration of miglitol in relation to the meal. Miglitol was administered 30 min before, just before, or both 30 min and just before a meal. In the case of administration just before a meal, insulin secretion was suppressed, although hypoglycemia was not prevented. Administration of the drug 30 min before a meal prevented postprandial hypoglycemia by slowing the increase of the blood glucose and serum insulin levels following the meal to a greater degree than administration just before a meal. Miglitol administration both 30 min and just before a meal caused an even smoother increase in blood glucose and serum insulin levels following the meal. In this report, we propose a new therapeutic approach for reactive hypoglycemia after gastrectomy, namely, administration of miglitol 30 min before meals. PMID- 25142088 TI - UBC13, an E2 enzyme for Lys63-linked ubiquitination, functions in root development by affecting auxin signaling and Aux/IAA protein stability. AB - Unlike conventional lysine (K) 48-linked polyubiquitination, K63-linked polyubiquitination plays signaling roles in yeast and animals. Thus far, UBC13 is the only known ubiquitin-conjugating enzyme (E2) specialized in K63-linked polyubiquitination. Previous identification of Arabidopsis genes encoding UBC13 as well as its interacting partner UEV1 indicates that the UBC13-mediated ubiquitination pathway is conserved in plants; however, little is known about functions and signaling mediated through K63-linked polyubiquitination in plants. To address the functions of UBC13-mediated ubiquitination in plants, we created Arabidopsis ubc13 null mutant lines in which the two UBC13 genes were disrupted. The double mutant displayed altered root development, including shorter primary root, fewer lateral roots and only a few short root hairs in comparison with the wild type and single mutant plants, indicating that UBC13 activity is critical for all major aspects of root development. The double mutant plants were insensitive to auxin treatments, suggesting that the strong root phenotypes do not simply result from a reduced level of auxin. Instead, the ubc13 mutant had a reduced auxin response, as indicated by the expression of an auxin-responsive DR5 promoter-GFP. Furthermore, both the enzymatic activity and protein level of an AXR3/IAA17-GUS reporter were greatly increased in the ubc13 mutant, whereas the induction of many auxin-responsive genes was suppressed. Collectively, these results suggest that Aux/IAA proteins accumulate in the ubc13 mutant, resulting in a reduced auxin response and defective root development. Hence, this study provides possible mechanistic links between UBC13-mediated protein ubiquitination, root development and auxin signaling. PMID- 25142089 TI - Introducing the SLI debate. PMID- 25142090 TI - Ten questions about terminology for children with unexplained language problems. AB - BACKGROUND: In domains other than language, there is fairly consistent diagnostic terminology to refer to children's developmental difficulties. For instance, the terms 'dyslexia', 'attention deficit hyperactivity disorder' and 'autistic spectrum disorder' are used for difficulties with reading, attention or social cognition, respectively. There is no agreed label, however, for children with unexplained language problems. AIMS: To consider whether we need labels for unexplained language problems in children, and if so, what terminology is appropriate. MAIN CONTRIBUTION: There are both advantages and disadvantages to labels, but they are important to ensure children receive services, and to increase our knowledge of the nature and causes of such problems. A survey of labels in current use found 132 different terms, 33 of which had 600 or more returns on Google Scholar between 1994 and 2013. Many of these labels were too general to be useful. Of the remainder, the term 'specific language impairment' was the most commonly used. CONCLUSIONS: The current mayhem in diagnostic labels is unsustainable; it causes confusion and impedes research progress and access to appropriate services. We need to achieve consensus on diagnostic criteria and terminology. The DSM-5 term 'language disorder' is problematic because it identifies too wide a range of conditions on an internet search. One solution is to retain specific language impairment, with the understanding that 'specific' means idiopathic (i.e., of unknown origin) rather than implying there are no other problems beyond language. Other options are the terms 'primary language impairment', 'developmental language disorder' or 'language learning impairment'. PMID- 25142091 TI - Specific language impairment: a convenient label for whom? AB - BACKGROUND: The term 'specific language impairment' (SLI), in use since the 1980s, describes children with language impairment whose cognitive skills are within normal limits where there is no identifiable reason for the language impairment. SLI is determined by applying exclusionary criteria, so that it is defined by what it is not rather than by what it is. The recent decision to not include SLI in DSM-5 provoked much debate and concern from researchers and clinicians. AIMS: To explore how the term 'specific language impairment' emerged, to consider how disorders, including SLI, are generally defined and to explore how societal changes might impact on use the term. METHODS & PROCEDURES: We reviewed the literature to explore the origins of the term 'specific language impairment' and present published evidence, as well as new analyses of population data, to explore the validity of continuing to use the term. OUTCOMES & RESULTS AND CONCLUSIONS & IMPLICATIONS: We support the decision to exclude the term 'specific language impairment' from DSM-5 and conclude that the term has been a convenient label for researchers, but that the current classification is unacceptably arbitrary. Furthermore, we argue there is no empirical evidence to support the continued use of the term SLI and limited evidence that it has provided any real benefits for children and their families. In fact, the term may be disadvantageous to some due to the use of exclusionary criteria to determine eligibility for and access to speech pathology services. We propose the following recommendations. First, that the word 'specific' be removed and the label 'language impairment' be used. Second, that the exclusionary criteria be relaxed and in their place inclusionary criteria be adopted that take into account the fluid nature of language development particularly in the preschool period. Building on the goodwill and collaborations between the clinical and research communities we propose the establishment of an international consensus panel to develop an agreed definition and set of criteria for language impairment. Given the rich data now available in population studies it is possible to test the validity of these definitions and criteria. Consultation with service users and policy-makers should be incorporated into the decision-making process. PMID- 25142092 TI - Terminological debate over language impairment in children: forward movement and sticking points. AB - BACKGROUND: There is no agreed terminology for describing childhood language problems. In this special issue Reilly et al. and Bishop review the history of the most widely used label, 'specific language impairment' (SLI), and discuss the pros and cons of various terms. Commentators from a range of backgrounds, in terms of both discipline and geographical background, were then invited to respond to each lead article. AIMS: To summarize the main points made by the commentators and identify (1) points of consensus and disagreement, (2) issues for debate including the drivers for change and diagnostic criteria, and (3) the way forward. CONCLUSIONS & IMPLICATIONS: There was some common ground, namely that the current situation is not tenable because it impedes clinical and research progress and impacts on access to services. There were also wide-ranging disagreements about which term should be adopted. However, before debating the broad diagnostic label it is essential to consider the diagnostic criteria and the systems used to classify childhood language problems. This is critical in order to facilitate communication between and among clinicians and researchers, across sectors (in particular health and education), with the media and policy makers and with families and individuals who have language problems. We suggest four criteria be taken into account when establishing diagnostic criteria, including: (1) the features of language, (2) the impact on functioning and participation, (3) the presence/absence of other impairments, and (4) the language trajectory or pathway and age of onset. In future, these criteria may expand to include the genetic and neural markers for language problems. Finally, there was overarching agreement about the need for an international and multidisciplinary forum to move this debate forward. The purpose would be to develop consensus regarding the diagnostic criteria and diagnostic label for children with language problems. This process should include canvassing the views of families and people with language problems as well as the views of policy makers. PMID- 25142093 TI - Influence of proton pump inhibitors and VKORC1 mutations on CYP2C9-mediated dose requirements of vitamin K antagonist therapy: a pilot study. AB - Interindividual variations in dose requirements of oral vitamin K antagonists (VKA) are attributed to several factors, including genetic variant alleles of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9), but also interaction with co-medications. In this context, proton pump inhibitor (PPI)-related alterations of VKA maintenance dose requirements have been published. The present investigation aimed to test for an interaction profile of oral VKA-therapy and PPIs in relation to the CYP2C9 genotype. Median weekly stable VKA dose requirements over 1 year were recorded in 69 patients. Patients were genotyped for CYP2C9*2, CYP2C9*3, VKORC1c.-1639G>A and VKORC1c.174 136C>T and assessed for an association with PPI use and total VKA maintenance dose requirements. PPI users with CYP2C9 genetic variations required significantly lower weekly VKA maintenance doses than those with the wild-type genotype (t-test: P = 0.02). In contrast, in subjects without PPI use, the CYP2C9 genotype had no significant influence on oral VKA dose requirements. Further, the combined CYP2C9/VKORC1 genotype was a significant predictor for VKA dose requirements [linear regression: estimate: -1.47, standard error: 0.58 (P = 0.01)]. In conclusion, in carriers of CYP2C9 gene variations, the interference with the VKA metabolism is modified by PPI co-medication and the VCKORC1 genotype. Preceding knowledge of the genetic profile and the awareness for potentially occurring severe over-anticoagulation problems under PPI co medication could contribute to a safer and personalized VKA pharmacotherapy. PMID- 25142094 TI - Ramping up the signal: promoting endurance training adaptation in skeletal muscle by nutritional manipulation. AB - Mitochondrial biogenesis in skeletal muscle results from the cumulative effect of transient increases in mRNA transcripts encoding mitochondrial proteins in response to repeated exercise sessions. This process requires the coordinated expression of both nuclear and mitochondrial (mt) DNA genomes and is regulated, for the most part, by the peroxisome proliferator-activated receptor gamma coactivator 1alpha. Several other exercise-inducible proteins also play important roles in promoting an endurance phenotype, including AMP-activated protein kinase, p38 mitogen-activated protein kinase and tumour suppressor protein p53. Commencing endurance-based exercise with low muscle glycogen availability results in greater activation of many of these signalling proteins compared with when the same exercise is undertaken with normal glycogen concentration, suggesting that nutrient availability is a potent signal that can modulate the acute cellular responses to a single bout of exercise. When exercise sessions are repeated in the face of low glycogen availability (i.e. chronic training), the phenotypic adaptations resulting from such interventions are also augmented. PMID- 25142095 TI - Chronic high-fat diet increases acute neuroendocrine stress response independently of prenatal dexamethasone treatment in male rats. AB - OBJECTIVE: Intrauterine growth restriction (IUGR) has been associated with metabolic disorders later in life such as obesity and diabetes as well as psychiatric disorders such as depression and schizophrenia. Therefore, we wanted to investigate whether behavioural, metabolic or neuroendocrine abnormalities could be provoked or exacerbated by a high-fat diet (HFD) in an experimental model of IUGR. METHODS: Pregnant dams were exposed to dexamethasone (DEX) in the third gestational week to induce IUGR. Late adolescent male offspring of DEX- and vehicle-treated dams were then fed a HFD or standard chow for 8 weeks and subjected to a variety of assessments. RESULTS: Only diet affected the hypothalamus-pituitary-adrenal (HPA) axis stress response, as HFD doubled the observed corticosterone levels following acute restraint. HFD and prenatal DEX exposure concomitantly exacerbated depressive-like behaviour in the forced swim test, even though no interaction was seen. Prenatal DEX treatment tended to increase the basal acoustic startle response (ASR), while an interaction between HFD and DEX was present in the ASR pre-pulse inhibition suggestive of fundamental changes in neuronal gating mechanisms. Metabolic parameters were only affected by diet, as HFD increased fasting glucose and insulin levels. CONCLUSION: We conclude that chronic HFD may be more important in programming of the HPA axis stress responsiveness than an adverse foetal environment and therefore potentially implies an increased risk for developing psychiatric and metabolic disease. PMID- 25142096 TI - Mitigating aggressiveness through education? The monoamine oxidase A genotype and mental health in general population. AB - OBJECTIVE: Monoamine oxidase A (MAOA) gene promoter region includes a variable number of tandem repeat (VNTR) associated with antisocial behaviour in adverse environment. We have examined the effect of the MAOA-uVNTR on mental health and academic success by using a population representative sample and a longitudinal design. METHODS: The data of the older cohort (n = 593, aged 15 years at the original sampling) of the longitudinal Estonian Children Personality, Behaviour and Health Study (ECPBHS) were used. Follow-ups were conducted at ages 18 and 25 years. Aggressiveness, inattention and hyperactivity were reported by class teachers or, at older age, self-reported. Stressful life events, psychological environment in the family and interactions between family members were self reported. Data of general mental abilities and education were obtained at the age of 25, and lifetime psychiatric disorder assessment was carried out with the Mini International Neuropsychiatric Interview (MINI) interview. RESULTS: MAOA-uVNTR genotype had no independent effect on aggressiveness, hyperactive and inattentive symptoms, and neither was there a genotype interaction with adverse life events. Interestingly, the proportion of male subjects with higher education by the age of 25 was significantly larger among those with MAOA low-activity alleles (chi2 = 7.13; p = 0.008). Logistic regression revealed that MAOA low-activity alleles, higher mental abilities, occurrence of anxiety disorders and absence of substance use disorder were significant independent predictors for higher education in male subjects. CONCLUSIONS: In a population representative sample of young subjects, the MAOA-uVNTR 'risk genotype' predicted better life outcomes as expressed in higher level of education. PMID- 25142097 TI - Chronic oral carbamazepine treatment elicits mood-stabilising effects in mice. AB - OBJECTIVE: The underlying biology of bipolar disorder and the mechanisms by which effective medications induce their therapeutic effects are not clear. Appropriate use of animal models are essential to further understand biological mechanisms of disease and treatment, and further understanding the therapeutic mechanism of mood stabilisers requires that clinically relevant administration will be effective in animal models. The clinical regimens for mood-stabilising drugs include chronic oral administration; however, much of the work with animal models includes acute administration via injection. An effective chronic and oral administration of the prototypic mood stabiliser lithium was already established and the present study was designed to do the same for the mood stabiliser carbamazepine. METHODS: Mice were treated for 3 weeks with carbamazepine in food. ICR mice were treated with 0.25%, 0.5% and 0.75%, and C57bl/6 mice with 0.5% and 0.75%, carbamazepine in food (w/w, namely, 2.5, 5.0 or 7.5 g/kg food). Mice were then tested for spontaneous activity, forced swim test (FST), tail suspension test (TST) and amphetamine-induced hyperactivity. RESULTS: Oral carbamazepine administration resulted in dose-dependent blood levels reaching 3.65 MUg/ml at the highest dose. In ICR mice, carbamazepine at the 0.5% dose had no effect on spontaneous activity, but significantly reduced immobility in the TST by 27% and amphetamine-induced hyperactivity by 28%. In C57bl/6 mice, carbamazepine at the 0.75% dose reduced immobility time in the FST by 26%. CONCLUSIONS: These results demonstrate a behaviourally effective oral and chronic regimen for carbamazepine with mood stabilising-like activity in a standard model for mania-like behaviour and two standard models for depression-like behaviour. PMID- 25142098 TI - Dopamine D(2/3) receptor availability and human cognitive impulsivity: a high resolution positron emission tomography imaging study with [11C]raclopride. AB - OBJECTIVE: Human impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioural aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. In this study, we investigated the relationship between self-reported impulsiveness and dopamine D(2/3) receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [11C]raclopride. METHODS: Twenty-one participants completed 3-T magnetic resonance imaging and high-resolution PET scans with [11C]raclopride. The trait of impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11). Partial correlation analysis was performed between BIS-11 scores and D(2/3) receptor availability in striatal subregions, controlling for the confounding effects of temperament characteristics that are conceptually or empirically related to dopamine, which were measured by the Temperament and Character Inventory. RESULTS: The analysis revealed that the non-planning (p = 0.004) and attentional (p = 0.007) impulsiveness subscale scores on the BIS-11 had significant positive correlations with D(2/3) receptor availability in the pre commissural dorsal caudate. There was a tendency towards positive correlation between non-planning impulsiveness score and D(2/3) receptor availability in the post-commissural caudate. CONCLUSION: These results suggest that cognitive subtrait of impulsivity is associated with D(2/3) receptor availability in the associative striatum that plays a critical role in cognitive processes involving attention to detail, judgement of alternative outcomes, and inhibitory control. PMID- 25142099 TI - Evaluation of acetylcholinesterase activity and behavioural alterations induced by ketamine in an animal model of schizophrenia. AB - OBJECTIVE: Cognitive deficits in schizophrenia play a crucial role in its clinical manifestation and seem to be related to changes in the cholinergic system, specifically the action of acetylcholinesterase (AChE). Considering this context, the aim of this study was to evaluate the chronic effects of ketamine in the activity of AChE, as well as in behavioural parameters involving learning and memory. METHODS: The ketamine was administered for 7 days. A duration of 24 h after the last injection, the animals were submitted to behavioural tests. The activity of AChE in prefrontal cortex, hippocampus and striatum was measured at different times after the last injection (1, 3, 6 and 24 h). RESULTS: The results indicate that ketamine did not affect locomotor activity and stereotypical movements. However, a cognitive deficit was observed in these animals by examining their behaviour in inhibitory avoidance. In addition, an increase in AChE activity was observed in all structures analysed 1, 3 and 6 h after the last injection. Differently, serum activity of AChE was similar between groups. CONCLUSION: Chronic administration of ketamine in an animal model of schizophrenia generates increased AChE levels in different brain tissues of rats that lead to cognitive deficits. Therefore, further studies are needed to elucidate the complex mechanisms associated with schizophrenia. PMID- 25142100 TI - Serum lipid peroxidation markers are correlated with those in brain samples in different stress models. AB - OBJECTIVE: Stress can stimulate increased production of oxygen radicals. We investigated the correlations between serum levels of lipid peroxidation markers and those in brain samples in different stress models. METHODS: Animals (n = 96) were divided equally into eight groups: a control group and groups treated with vitamin E (Vit E); exposed to immobilisation stress; exposed to immobilisation stress and treated with Vit E; exposed to cold stress; exposed to cold stress and treated with Vit E; exposed to both immobilisation and cold stress; and a final group exposed to both immobilisation and cold stress and treated with Vit E. Thiobarbituric acid-reactive substance (TBARS) in brain samples and levels of TBARS, corticosterone, conjugated dienes (CD), lipids, and paraoxonase-1 (PON1) activity in serum were analysed. RESULTS: Serum corticosterone (p < 0.001), CD (p < 0.05), lipid (p < 0.05) levels, and brain TBARS (p < 0.05) levels were significantly higher in all stress groups than in controls, and the elevated levels were reversed in the Vit E-treated stress groups (p < 0.05). Serum PON1 activity was not different among the groups (p > 0.05). Serum TBARS levels increased significantly in all stress groups (p < 0.05), but this elevation was only reversed in the group exposed to both immobilisation and cold stress and treated with Vit E (p < 0.001). CONCLUSION: These results suggest that serum levels of lipid peroxidation markers can be determined readily and may be useful as indicators to evaluate the effects of oxidative stress in the brain. PMID- 25142101 TI - Loperamide overdose-induced catatonia: potential role of brain opioid system and P-glycoprotein. AB - OBJECTIVE: Catatonic features are observed in several psychiatric illnesses but can also be found following substance misuse. Loperamide is an anti-diarrhoeal medication that acts on opioid receptors in the intestine, reducing peristalsis. It is normally unable to pass through the intestinal wall or the blood-brain barrier; however, high dosages can in fact induce the effects on the central nervous system. CASE REPORT: We describe the case of a 20-year-old man who presented with severe catatonia following excessive intake of loperamide, fully remitted with lorazepam. CONCLUSION: We speculate on a possible increase of loperamide's bioavailability after overdose owing to reduced expression and functioning of P-glycoprotein. PMID- 25142102 TI - Suppression of antipsychotic-induced tardive dyskinesia with aripiprazole in an elderly patient with bipolar I disorder. AB - INTRODUCTION: Aripiprazole has a low risk for causing extrapyramidal syndrome and can remit neuroleptic-induced tardive dyskinesia (TD). Here, we presented a case in which TD was suppressed, but not cured, by long-term aripiprazole treatment. CASE: This 74-year-old male patient had bipolar I disorder and had developed TD many times after several antipsychotic treatments. The lowest chlorpromazine dose equivalent among the previous antipsychotic treatments was 25 mg/day of quetiapine. His TD always improved immediately after the dosage was shifted to aripiprazole. However, his insomnia or other psychiatric symptoms worsened the first three times when the treatment was shifted to aripiprazole, making the transition a failure. Before the fourth attempt of aripiprazole transition, the patient was in a euthymic state but again developed TD under olanzapine 10 mg/day treatment. During the fourth attempt of aripiprazole transition, his TD had remained in complete remission for more than 1 year after the dosage shifted to 10 mg/day of aripiprazole. He developed TD again when we tapered the aripiprazole dose to 5 mg/day, but his TD remitted when we restored his aripiprazole dose to 10 mg/day. CONCLUSION: Aripiprazole could be an effective drug in elderly bipolar patients with antipsychotic-induced TD while the patients are in a euthymic state. However, aripiprazole may only suppress TD rather than cure it. PMID- 25142103 TI - Reward processing in healthy offspring of parents with bipolar disorder. AB - IMPORTANCE: Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder. OBJECTIVE: To determine whether anomalous neural processing of reward characterizes children at familial risk for BD in the absence of a personal history of a psychopathologic disorder. DESIGN, SETTING, AND PARTICIPANTS: This study compared neural activity and behaviors of children at high and low risk for mania while they anticipate and respond to reward and loss. The study was performed from September 15, 2009, through February 17, 2012, in a university functional magnetic resonance imaging facility and included 8- to 15-year-old children without disorders born to a parent with BD (n = 20 high-risk children) and demographically matched healthy comparison children (n = 25 low-risk children). MAIN OUTCOMES AND MEASURES: Neural activity, as measured with functional magnetic resonance imaging, during anticipation and receipt of reward and loss during a monetary incentive delay task. RESULTS: While anticipating losses, high-risk children had less activation in the pregenual cingulate than did their low-risk counterparts (t19 = -2.44, P = .02). When receiving rewards, high-risk children had greater activation in the left lateral orbitofrontal cortex than did low-risk children (t43 = -3.04, P = .004). High-risk children also had weaker functional connectivity between the pregenual cingulate and the right ventrolateral prefrontal cortex while anticipating rewards than did low-risk children (t19 = -4.38, P < .001) but had a stronger connectivity between these regions while anticipating losses (t24 = 2.76, P = .01). Finally, in high- but not low-risk children, novelty seeking was associated with increased striatal and amygdalar activation in the anticipation of losses, and impulsivity was associated with increased striatal and insula activation in the receipt of rewards. CONCLUSIONS AND RELEVANCE: Aberrant prefrontal activations and connectivities during reward processing suggest mechanisms that underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania. Longitudinal studies are needed to examine whether these patterns of neural activation predict the onset of mania and other mood disorders in high-risk children. PMID- 25142105 TI - Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites. AB - Antibiotic-loaded bone cement is a primary option for treatment of orthopedic infections. Poly(methyl methacrylate) (PMMA) is a widely used cement that, when loaded with antibiotics in spacer or bead form, has been shown to reduce infection rates. However, PMMA is not resorbable and requires a second surgery for removal, while also acting as a potential foreign body for bacterial colonization. Alternatively, resorbable bone cements, such as calcium sulfate, have been proposed and present the advantage of being completely reabsorbed. It is unknown whether the antibiotic elution characteristics of absorbable bone cements are similar to PMMA. This study (1) characterized antibiotic elution from synthetic, highly purified calcium sulfate cement beads of varying sizes against pathogenic bacteria both in liquid culture and seeded on agar plates, (2) tested calcium sulfate beads against PMMA beads loaded with the same antibiotics, and (3) analyzed the structural differences between how PMMA and calcium sulfate bind to antibiotics. In every assay, the calcium sulfate beads performed as well as, or better than, the PMMA beads in inhibition of bacterial growth and elution of vancomycin in vitro with complete elution observed from calcium sulfate within three days. These data suggest that calcium sulfate, functions, as well as PMMA in the patient setting for infection control. PMID- 25142106 TI - Three-dimensional versus two-dimensional ultrasound for fetal nasal bone evaluation in the second trimester. AB - OBJECTIVES: To compare two-dimensional with three-dimensional ultrasound evaluation of the fetal nasal bone in the second trimester. METHODS: A prospective, non-interventional study was conducted, in 55 singleton fetuses, between 18 and 24 weeks' gestation. Fetal nasal bone length was measured in the midsagittal plane by two-dimensional imaging and in the midsagittal and coronal plane with three-dimensional ultrasound. All three measurements were compared with one another using one-way repeated samples-measures ANOVA and paired samples t-test. RESULTS: The average fetal nasal bone length (mean +/- SD) as determined by the three methods was 7.01 +/- 0.94 mm for the two-dimensional midsagittal, 6.96 +/- 1.34 mm for the three-dimensional midsagittal, and 6.98 +/- 1.32 mm for the three-dimensional coronal plane; comparisons between one another were not statistically significant. Unilateral hypoplasia and bifid shape of the fetal nasal bone were detected in 8.2% and 20.4% of cases, respectively, by three dimensional ultrasound, whereas all cases evaded detection with two-dimensional ultrasound (p < 0.001 and p = 0.001, respectively). CONCLUSIONS: Fetal nasal bone length measured with two-dimensional ultrasound does not differ significantly from three-dimensional measurements. However, three-dimensional ultrasound is superior in detecting unilateral nasal bone hypoplasia or absence and in assessing fetal nasal bone shape. Hence, fetal nasal bone examination in the second trimester should include three-dimensional ultrasound evaluation. PMID- 25142107 TI - Oxytocin discontinuation after the active phase of labor is established. AB - Despite the widespread usage of oxytocin, there is still no consensus on its mode of administration. The scope of the present meta-analysis was to assess the effect of oxytocin discontinuation after the active phase of labor is established on maternal fetal and neonatal outcomes. We searched Medline, Scopus, Popline, ClinicalTrials.gov and Google Scholar databases. Eight studies were finally retrieved, which involved 1232 parturient. We observed significantly decreased rates of cesarean sections among parturient that discontinued oxytocin (OR 0.51, 95% CI 0.35, 0.74) as well as decreased rates of uterine hyperstimulation (OR 0.33, 95% CI 0.19, 0.58). Similarly, cases of non-reassuring fetal heart rates were fewer among women that did not receive oxytocin after the establishment of the active phase of labor (OR 0.63, 95% CI 0.41, 0.97). Keeping in mind the aforementioned maternal and neonatal adverse effects that seem to result from infusion of oxytocin until delivery, future practice should aim towards its discontinuation after the establishment of the active phase of labor, as it does not seem to influence the total duration of labor. Future studies should aim towards specific populations of parturient in order to clarify whether different approaches are needed. PMID- 25142104 TI - Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass. AB - Diabetes is a common and significant co-morbidity in cystic fibrosis (CF). The pathogenesis of cystic fibrosis related diabetes (CFRD) is incompletely understood. Because exocrine pancreatic disease is similar between humans and pigs with CF, the CF pig model has the potential to contribute significantly to the understanding of CFRD pathogenesis. We determined the structure of the endocrine pancreas in fetal, newborn and older CF and non-CF pigs and assessed endocrine pancreas function by intravenous glucose tolerance test (IV-GTT). In fetal pigs, pancreatic insulin and glucagon density was similar between CF and non-CF. In newborn and older pigs, the insulin and glucagon density was unchanged between CF and non-CF per total pancreatic area, but increased per remnant lobular tissue in CF reflecting exocrine pancreatic loss. Although fasting glucose levels were not different between CF and non-CF newborns, CF newborns demonstrated impaired glucose tolerance and increased glucose area under the curve during IV-GTT. Second phase insulin secretion responsiveness was impaired in CF newborn pigs and significantly lower than that observed in non-CF newborns. Older CF pigs had elevated random blood glucose levels compared with non-CF. In summary, glycaemic abnormalities and insulin secretion defects were present in newborn CF pigs and spontaneous hyperglycaemia developed over time. Functional changes in CF pig pancreas were not associated with a decline in islet cell mass. Our results suggest that functional islet abnormalities, independent of structural islet loss, contribute to the early pathogenesis of CFRD. PMID- 25142108 TI - Rare congenital pulmonary malformation with diagnostic challenging: congenital pulmonary lymphangiectasia, report of four autopsy cases and review of literature. AB - Congenital pulmonary lymphangiectasia (CPL) is a rare congenital disorder that typically presents with intractable respiratory failure in the first few days of life. There is an association non-immun hydrops and CPL. In this study we reviewed four CPL cases between January 2006 and January 2014 among 684 fetal pediatric autopsies. All cases were in the second trimester. In light microscopy there were marked dilatated channels in the subpleural -peribronchial-subseptal region of the lungs. The channels were lined with flattened cells which were expressing CD 31 and D2-40, negative for CD34. Although pulmonary interstitial emphysema (PIE) was considered an important differential diagnosis, a giant cell reaction surrounding the interstitial cystic lesions, a histological hallmark of PIE. CPL is characterized by dilatation of the pulmonary lymphatic vessels and occurs as a congenital anomaly. Noonan classified it into three groups. Primary developmental defect of pulmonary lymphatics is group 3. Group 3 is called also as CPL; normal regression of the connective tissue elements fails to occur after the 16th week of fetal life, associated with an aggressive clinical course, poor prognosis. In fetal autopsy examination CPL should be recognized if there is a fetus with pleural effusion, non-immune hydrops. There is no clinical evidence for CPL. PMID- 25142109 TI - Placenta accreta is an independent risk factor for late pre-term birth and perinatal mortality. AB - OBJECTIVE: This study is aimed to identify the risk factors for the development of placenta accreta (PA) and characterize its effect on maternal and perinatal outcomes. STUDY DESIGN: This population-based retrospective cohort study included all deliveries at our medical center during the study period. Those with placenta accreta (n = 551) comprised the study group, while the rest of the deliveries (n = 239 089) served as a comparison group. RESULTS: The prevalence of placenta accerta is 0.2%. Women with this complication had higher rates of >=2 previous CS (p < 0.001), recurrent abortions (p = 0.03), and previous placenta accreta [p < 0.001]. The rates of placenta previa and peripartum hemorrhage necessitating blood transfusion were higher in women with placenta accreta than in the comparison group. PTB before 34 and 37 weeks of gestation was more common among women with placenta accreta (p < 0.01), as was the rate of perinatal mortality (p < 0.001). Placenta accreta was an independent risk factor for perinatal mortality (adj. OR 8.2; 95% CI 6.4-10.4, p < 0.001) and late PTB (adj. OR 1.4; 95% CI 1.1 1.7, p = 0.002). CONCLUSION: Placenta accreta is an independent risk factor for late PTB and perinatal mortality. PMID- 25142110 TI - Vortex-assisted surfactant-enhanced-emulsification liquid-liquid microextraction of biogenic amines in fermented foods before their simultaneous analysis by high performance liquid chromatography. AB - A simple, rapid, sensitive, and environmentally friendly method, based on modified dispersive liquid-liquid microextraction coupled with high-performance liquid chromatography was developed for the simultaneous determination of five biogenic amines in fermented food samples. Biogenic amines were derivatized with 9-fluorenylmethyl chloroformate, extracted by vortex-assisted surfactant-enhanced emulsification liquid-liquid microextraction, and then analyzed by high performance liquid chromatography. Five biogenic amine compounds were separated within 30 min using a C18 column and gradient elution with acetonitrile and 1% acetic acid. Factors influencing the derivatization and extraction efficiency such as type and volume of extraction solvent, type, and concentration of surfactant, pH, salt addition, and vortex time were optimized. Under the optimum conditions, the method provided the enrichment factors in the range of 161-553. Good linearity was obtained from 0.002-0.5 mg/L for cadaverine and tyramine, 0.003-1 mg/L for tryptamine and histamine, and 0.005-1 mg/L for spermidine with coefficient of determination (R(2) ) > 0.992. The limits of detection ranged from 0.0010 to 0.0026 mg/L. The proposed method was successfully applied to analysis of biogenic amines in fermented foods such as fermented fish (plaa-som), wine and beer where good recoveries were obtained in the range of 83.2-112.5% PMID- 25142111 TI - microRNA management of NK-cell developmental and functional programs. AB - NK cells are innate lymphoid cells that are critical for host defense against infection, and mediate anti-tumor responses. MicroRNAs (miRNAs) are a large family of small noncoding RNAs that target the 3' untranslated region (UTR) of mRNAs, thereby attenuating protein translation. The expression of miRNAs within human peripheral blood and mouse splenic NK cells has been cataloged, with the majority of the miRNA sequence pool represented in the top 60 most abundantly expressed miRNAs. Global miRNA deficiency within NK cells has confirmed their critical role in NK-cell biology, including defects in NK-cell development and altered functionality. Studies using gain- and loss-of-function of individual miRNAs in NK cells have demonstrated the role of specific miRNAs in regulating NK cell development, maturation, and activation. miRNAs also regulate fundamental NK cell processes including cytokine production, cytotoxicity, and proliferation. This review provides an update on the intrinsic miRNA regulation of NK cells, including miRNA expression profiles, as well as their impact on NK-cell biology. Additional profiling is needed to better understand miRNA expression within NK cell developmental intermediates, subsets, tissues, and in the setting of disease. Furthermore, key open questions in the field as well as technical challenges in the study of miRNAs in NK cells are highlighted. PMID- 25142120 TI - Synthesis, cytotoxicity, and phase-solubility study of cyclodextrin click clusters. AB - To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4 hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-beta-cyclodextrin (HT-beta-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl} beta-cyclodextrin (HT-beta-CD(OMe)2 ), and heptakis{6-(4-sulfonylmethyl-1H [1,2,3]triazol-1-yl)-6-deoxy}-beta-cyclodextrin (ST-beta-CD). The CCCs were prepared using copper(I)-catalyzed azide-alkyne cycloaddition from 6-azido-6 deoxy-beta-CD and their water solubility, cytotoxicity, and drug-solubilizing effect were investigated. Water turbidity testing of the CCCs showed that the minimum water solubility of the CCCs is at least 20 times higher than that of beta-CD. An MTT cell viability assay performed on HeLa cells demonstrated a low cytotoxicity of the CCCs compared with 2,6-dimethyl-beta-cyclodextrin. HT-beta CD(OMe)2 and ST-beta-CD did not demonstrate any cytotoxicity within the experimental concentration (~5 mM) like 2-hydroxypropyl-beta-CD. A phase solubility study of prednisolone with the CCCs suggested that CCCs showed increased solubility of prednisolone in the presence of increasing concentrations of the CCCs. The comparison between the conventional CD derivatives and CCCs on solubility, cytotoxicity, and binding property implies that CCCs are alternative cyclodextrin derivatives useful for overcoming the restrictions of conventional cyclodextrin chemistry. PMID- 25142119 TI - Optimization of STR locus enrichment for STR profiling of fragmented DNA. AB - DNA degradation is a major obstacle in gaining an accurate profile with standard DNA typing technology. Although alternative genotyping strategies such as mini STRs and SNPs have proven to be more successful in profiling degraded DNA, these approaches also have limitations. Here, we show that locus enrichment by hybridization of degraded genomic DNA with an STR locus-specific biotinylated oligonucleotide is a powerful approach to overcome problems in STR typing of highly degraded DNA. An experimental investigation of factors affecting the efficiency of this method indicates that the choice of primer and molar ratio of primers to genomic DNA are critical factors in improving enrichment of the STR locus before genotyping with multiplex kits. In addition, we find that indirect capture rather than direct capture with magnetic beads yields better enrichment efficiency for STR locus enrichments. Using these strategies, we demonstrate an improvement in STR typing of DNA from cultured cells damaged by exposure to sunlight or UV. We suggest that this approach could be applied to highly degraded forensic samples alone or in combination with mini-STRs. PMID- 25142121 TI - Effects of structured heart failure disease management on mortality and morbidity depend on patients' mood: results from the Interdisciplinary Network for Heart Failure Study. AB - AIMS: Depression is common in heart failure (HF) and associated with adverse outcomes. Randomized comparisons of the effectiveness of HF care strategies by patients' mood are scarce. We therefore investigated in a randomized trial a structured collaborative disease management programme (HeartNetCare-HFTM; HNC) recording mortality, morbidity, and symptoms in patients enrolled after hospitalization for decompensated systolic HF according to their responses to the 9-item Patient Health Questionnaire (PHQ-9) during an observation period of 180 days. METHODS AND RESULTS: Subjects scoring <12/>=12 were categorized as non depressed/depressed, and those ignoring the questionnaire as PHQ-deniers. Amongst 715 participants (69 +/- 12 years, 29% female), 141 (20%) were depressed, 466 (65%) non-depressed, and 108 (15%) PHQ-deniers. The composite endpoint of mortality and re-hospitalization was neutral overall and in all subgroups. However, HNC reduced mortality risk in both depressed and non-depressed patients [adjusted hazard ratios (HRs) 0.12, 95% confidence interval (CI) 0.03-0.56, P = 0.006, and 0.49, 95% CI 0.25-0.93, P = 0.03, respectively], but not in PHQ deniers (HR 1.74, 95% CI 0.77-3.96, P = 0.19; P = 0.006 for homogeneity of HRs). Average frequencies of patient contacts in the HNC arm were 12.8 +/- 7.9 in non depressed patients, 12.4 +/- 7.1 in depressed patients, and 5.5 +/- 7.2 in PHQ deniers (P < 0.001). CONCLUSIONS: Early after decompensation, HNC reduced mortality risk in non-depressed and even more in depressed subjects, but not in PHQ-deniers. This suggests that differential acceptability and chance of success of care strategies such as HNC might be predicted by appropriate assessment of patients' baseline characteristics including psychological disposition. These post-hoc results should be reassessed by prospective evaluation of HNC in larger HF populations. PMID- 25142122 TI - Spatiotemporal dynamics of affective picture processing revealed by intracranial high-gamma modulations. AB - Our comprehension of the neural mechanisms underlying emotional information processing has largely benefited from noninvasive electrophysiological and functional neuroimaging techniques in recent years. However, the spatiotemporal dynamics of the neural events occurring during emotional processing remain imprecise due to the limited combination of spatial and temporal resolution provided by these techniques. This study examines the modulations of high frequency activity of intracranial electroencephalography recordings associated with affective picture valence, in epileptic patients awaiting neurosurgery. Recordings were obtained from subdural grids and depth electrodes in eight patients while they viewed a series of unpleasant, pleasant and neutral pictures from the International Affective Picture System. Broadband high-gamma (70-150 Hz) power was computed for separate 100-ms time windows and compared according to ratings of emotional valence. Compared to emotionally neutral or pleasant pictures, unpleasant stimuli were associated with an early and long-lasting (~200 1,000 ms) bilateral increase in high-gamma activity in visual areas of the occipital and temporal lobes, together with a late and transient (~500-800 ms) decrease found bilaterally in the lateral prefrontal cortex (PFC). Pleasant pictures were associated with increased gamma activity in the occipital cortex, compared to the emotionally neutral stimuli. Consistent with previous studies, our results provide direct evidence of emotion-related modulations in the visual ventral pathway during picture processing. Results in the lateral PFC also shed light on the neural mechanisms underlying its role in negative emotions processing. This study demonstrates the utility of intracranial high-gamma modulations to study emotional process with a high spatiotemporal precision. PMID- 25142124 TI - Conformational problem of alkanes in liquid crystals by NMR spectroscopy: a mini review. AB - Recent discoveries of the role of alkane flexibility in determining liquid crystal behaviour are surveyed. With the impetus for understanding the alkane conformational problem established, recent model dependent (1)H NMR work on the topic will be reviewed where progress is made but the need to circumvent models eventually becomes evident. A closer look at the rigid basic units of alkanes will provide the way forward where it is shown that the orientational ordering and anisotropic potentials of these molecules dissolved in liquid crystals scale with each other. Once this relationship is established, a series of works using anisotropic and isotropic (1)H NMR spectroscopy to study alkane conformational statistics will be covered, wherein the influence of the gas, isotropic condensed and anisotropic condensed phases will be described. PMID- 25142123 TI - Urinary monocyte chemotactic protein-1 (MCP-1) in leprosy patients: increased risk for kidney damage. AB - BACKGROUND: We aimed to evaluate urinary MCP-1 and oxidative stress through urinary malondialdehyde (MDA) in leprosy and correlate them with traditional, but less sensitive markers of renal disease. METHODS: This is a cross-sectional study of 44 patients with diagnosis of leprosy and no previous treatment. Skin smear was assessed through a bacteriological index - from 0 to 6+. Glomerular filtration rate (GFR), protein excretion rate, microalbuminuria, urinary oxidative stress, malondialdehyde (MDA) and urinary MCP-1 were measured. Also, high- sensitivity C-reactive protein (hs-CRP) was measured in the blood. Fifteen healthy subjects composed a control group. RESULTS: Age and gender were similar between leprosy patients and control groups. No patient had a GFR < 60 mL/min/1.73 m2 or albumin excretion rate greater than 30 mg/g-Cr. Leprosy patients had higher urinary protein excretion (97.6 +/- 69.2 vs. 6.5 +/- 4.3 mg/g Cr, p < 0.001), urinary MCP-1 (101.0 +/- 79.8 vs. 34.5 +/- 14.9 mg/g-Cr, p = 0.006) and urinary MDA levels (1.77 +/- 1.31 vs. 1.27 +/- 0.66 mmol/g-Cr, p = 0.0372) than healthy controls. There was a positive correlation between urinary MCP-1 and bacteriological index in skin smears (r = 0.322, p = 0.035), urinary protein excretion (r = 0.547, p < 0.001), albumin excretion rate (r = 0.414, p = 0.006) and urinary MDA (r = 0.453, p = 0.002). After adjusting for hs-CRP, urinary MCP-1 remained correlated with albumin excretion rate (rpartial = 0.483, p = 0.007) and MDA levels (rpartial = 0.555, p = 0.001). CONCLUSION: Leprosy patients with no clinical kidney disease have increased urinary MCP-1 mainly in lepromatous polar form. Inflammatory (MCP-1) and oxidative stress markers suggest leprosy patients are at high risk of developing kidney disease. PMID- 25142125 TI - Population projections: why they are often wrong. PMID- 25142126 TI - Cytidine deamination and cccDNA degradation: A new approach for curing HBV? PMID- 25142127 TI - Characterisation of a micro-plasma for ambient mass spectrometry imaging. AB - Results are presented on the characterisation and optimisation of a non-thermal atmospheric pressure micro-plasma ion source used for ambient mass spectrometry imaging. The geometry of the experiment is optimised to produce the most intense and stable ion signals. Signal stabilities (relative standard deviation) of 2.3 6.5% are achieved for total ion current measurements from chromatograms. Parameters are utilised to achieve MS imaging by raster scanning of PTFE/glass samples with a spatial resolution of 147 +/- 31 MUm. A systematic study of resolution as a function of acquisition parameters was also undertaken to underpin future technique development. Mass spectra are obtained from PTFE/glass sample edges in negative ion mode and used to construct images to calculate the spatial resolution. Images are constructed using the intensity variation of the dominant ion observed in the PTFE spectrum. Mass spectra originating from the polymer are dominated by three series of ions in a m/z spectral window from 200 500 Da. These ions are each separated by 50 Da and have the chemical formula [C2F + [CF2]n](-), [CF + [CF2]n + O](-) and [CF + [CF2]n + O3](-). The mechanism for the generation of these ions appears to be a polymer chain scission followed by ionisation by atmospheric ion adduction. Positive and negative ion mode mass spectra of personal care products, amino acids and pharmaceuticals, dominated by the proton abstracted/protonated molecular ion, highlight the potential areas of application for such a device. Further to this end a mass spectral image of cardamom seeds, constructed using the variation in intensity of possible fragments of the 1,8-cineole molecule, is included to reveal the potential application to the imaging of foods and other biological materials. PMID- 25142128 TI - Decreased susceptibility to false memories from misinformation in hormonal contraception users. AB - Sex hormones are increasingly implicated in memory formation. Recent literature has documented a relationship between hormones and emotional memory and sex differences, which are likely related to hormones, have long been demonstrated in a variety of mnemonic domains, including false memories. Hormonal contraception (HC), which alters sex hormones, has been associated with a bias towards gist memory and away from detailed memory in women who use it during an emotional memory task. Here, we investigated whether HC was associated with changes in susceptibility to false memories, which may be related to the formation of gist memories. We tested false memory susceptibility using two well-validated false memory paradigms: the Deese-Roediger-McDermott (DRM) task, and a story-based misinformation task. We found that hormonal contraceptive users were less susceptible to false memories compared to non-users in the misinformation task, and no differences were seen between groups on the DRM task. We hypothesise that the differences in false memories from the misinformation task may be related to hormonal contraceptive users' memory bias away from details, towards gist memory. PMID- 25142129 TI - Oral administration of soluble guanylate cyclase agonists to rats results in osteoclastic bone resorption and remodeling with new bone formation in the appendicular and axial skeleton. AB - Orally administered small molecule agonists of soluble guanylate cyclase (sGC) induced increased numbers of osteoclasts, multifocal bone resorption, increased porosity, and new bone formation in the appendicular and axial skeleton of Sprague-Dawley rats. Similar histopathological bone changes were observed in both young (7- to 9-week-old) and aged (42- to 46-week-old) rats when dosed by oral gavage with 3 different heme-dependent sGC agonist (sGCa) compounds or 1 structurally distinct heme-independent sGCa compound. In a 7-day time course study in 7- to 9-week-old rats, bone changes were observed as early as 2 to 3 days following once daily compound administration. Bone changes were mostly reversed following a 14-day recovery period, with complete reversal after 35 days. The mechanism responsible for the bone changes was investigated in the thyroparathyroidectomized rat model that creates a low state of bone modeling and remodeling due to deprivation of thyroid hormone, calcitonin (CT), and parathyroid hormone (PTH). The sGCa compounds tested increased both bone resorption and formation, thereby increasing bone remodeling independent of calciotropic hormones PTH and CT. Based on these studies, we conclude that the bone changes in rats were likely caused by increased sGC activity. PMID- 25142130 TI - Geometrical structure and interface dependence of bias stress induced threshold voltage shift in C60-based OFETs. AB - The influence of the nature of interface between organic semiconductor and gate dielectric on bias stress electrical stability of n-type C60-based organic field effect transistors (OFETs) was studied. The bias stress induced threshold voltage (Vth) shift was found to depend critically on the OFET device structure: the direction of V(th) shift in top-gate OFETs was opposite to that in bottom-gate OFETs, while the use of the dual-gate OFET structure resulted in just very small variations in V(th). The opposite direction of Vth shift is attributed to the different nature of interfaces between C60 semiconductor and Parylene dielectric in these devices. The V(th) shift to more positive voltages upon bias stress in bottom-gate C60-OFET was similar to that observed for other n-type semiconductors and rationalized by electron trapping in the dielectric or at the gate dielectric/C60 interface. The opposite direction of Vth shift in top-gate C60 OFETs is attributed to free radical species created in the course of Parylene deposition on the surface of C60 during device fabrication, which produce plenty of hole traps. It was also realized that the dual-gate OFETs gives stable characteristics, which are immune to bias stress effects. PMID- 25142132 TI - Composition of fatty acids, triacylglycerols and polar compounds of different walnut varieties (Juglans regia L.) from Tunisia. AB - The chemical composition (total oil content, fatty acids, triacylglycerols (TAGs) and polar compounds) of six walnuts (Juglans regia L.) cultivars (Lauzeronne, Franquette, Hartley, Local pt, Local gd and Parisienne) collected from Mateur (north of Tunisia) was evaluated. The major fatty acids found in the walnut oils are linoleic acid (60.42-65.77%), oleic acid (13.21-19.94%) and linolenic acid (7.61-13%). The TAG species were mainly composed of trilinolein (LLL), dilinoleoyl-linolenoyl-glycerol, dilinoleoyl-oleoyl-glycerol and palmitoyl dilinoleoyl-glycerol classes. The results revealed that Local pt variety has the highest level of oil (62.56%), linoleic acid (65.77%) and LLL (33.48%). Significant differences among oil samples were observed, therefore showing a great variability in the oil composition among cultivars. PMID- 25142133 TI - Patients' experience of outsourcing and care related to magnetic resonance examinations. AB - BACKGROUND: Outsourcing radiological examinations from public university hospitals affects the patient, who has to attend a different clinic or hospital for the radiological examination. We currently have a limited understanding of how patients view outsourcing and their care related to MR examinations. AIM: To examine the experiences of patients who are sent to private radiology units when their referrals for MR examinations are outsourced from a university hospital, as well as to explore factors which influence patient satisfaction regarding the quality of care related to the MR examination. METHODS: A group of patients (n = 160) referred for MR examinations and either examined at a university hospital or at an external private unit were interviewed. The interview was designed as a verbal questionnaire. Data were analyzed using Student's t test, analysis of variance (ANOVA), and Pearson's correlation. RESULTS: Sixty-nine percent of the patients could neither choose nor influence the location at which they were examined. For those who could, aspects that influenced the patient's choice of radiology department were: short waiting time 79% (127/160), ease of traveling to the radiology department 68% (110/160), and short distance to their home or work 58% (93/160). For 40% (60/160) of the patients, a short time in the waiting room was related to a positive experience of the MR examination. CONCLUSION: If patients were informed about outsourcing and could also choose where to have their examination, key factors contributing to patient satisfaction could be met even when MR examinations are outsourced. PMID- 25142134 TI - Boronic acid shell-crosslinked dextran-b-PLA micelles for acid-responsive drug delivery. AB - Herein, 3-carboxy-5-nitrophenylboronic acid (CNPBA) shell-crosslinked micelles based on amphiphilic dextran-block-polylactide (Dex-b-PLA) are prepared and used for efficient intracellular drug deliveries. Due to the reversible pH-dependent binding with diols to form boronate esters, CNPBA modified Dex-b-PLA shows excellent pH-sensitivity. In neutral aqueous conditions, CNPBA-Dex-b-PLA forms shell-crosslinked micelles to enable DOX loading, while in acid conditions, the boronate esters hydrolyze and the micelles de-crosslink to release loaded DOX. In vitro release studies indicate that the release of the DOX cargo is minimized at physiological conditions, while there is a burst release in response to low pHs. The cell viability of CNPBA-Dex-b-PLA investigated by MTT assay was more than 90%, indicating that, as a drug delivery system, CNPBA-Dex-b-PLA has good cytocompatibility. These features suggest that the pH-responsive biodegradable CNPBA-Dex-b-PLA can efficiently load and deliver DOX into tumor cells and enhance the inhibition of cellular proliferation in vitro, providing a favorable platform as a drug delivery system for cancer therapy. PMID- 25142131 TI - Development of echolocation calls and neural selectivity for echolocation calls in the pallid bat. AB - Studies of birdsongs and neural selectivity for songs have provided important insights into principles of concurrent behavioral and auditory system development. Relatively little is known about mammalian auditory system development in terms of vocalizations or other behaviorally relevant sounds. This review suggests echolocating bats are suitable mammalian model systems to understand development of auditory behaviors. The simplicity of echolocation calls with known behavioral relevance and strong neural selectivity provides a platform to address how natural experience shapes cortical receptive field (RF) mechanisms. We summarize recent studies in the pallid bat that followed development of echolocation calls and cortical processing of such calls. We also discuss similar studies in the mustached bat for comparison. These studies suggest: (1) there are different developmental sensitive periods for different acoustic features of the same vocalization. The underlying basis is the capacity for some components of the RF to be modified independent of others. Some RF computations and maps involved in call processing are present even before the cochlea is mature and well before use of echolocation in flight. Others develop over a much longer time course. (2) Normal experience is required not just for refinement, but also for maintenance, of response properties that develop in an experience independent manner. (3) Experience utilizes millisecond range changes in timing of inhibitory and excitatory RF components as substrates to shape vocalization selectivity. We suggest that bat species and call diversity provide a unique opportunity to address developmental constraints in the evolution of neural mechanisms of vocalization processing. PMID- 25142135 TI - Mild copper-TBAF-catalyzed N-arylation of sulfoximines with aryl siloxanes. AB - An efficient copper-TBAF-catalyzed C-N bond formation of sulfoximines with arylsiloxanes in dichloromethane at room temperature, affording the desired N aryl sulfoximines in good to excellent yields under an oxygen atmosphere, is reported. This method complements the existing synthetic approaches due to some advantageous properties of arylsiloxanes such as availability, low toxicity, ease of handling, high stability, and environmental benignity under mild reaction conditions, thus opening a new approach to practical C-N bond formation. PMID- 25142136 TI - Population genetics of forest type of Trypanosoma congolense circulating in Glossina palpalis palpalis of Fontem in the South-West region of Cameroon. AB - BACKGROUND: Genetic variation of microsatellite loci is a widely used method for the analysis of population genetic structure of several organisms. To improve our knowledge on the population genetics of trypanosomes, Trypanosoma congolense forest and savannah types were identified in the mid-guts of Glossina palpalis palpalis caught in five villages of Fontem in the South-West region of Cameroon. From the positive samples of Trypanosoma congolense forest, the genetic diversity and the population genetic structure of these parasites were evaluated. METHOD: For this study, pyramidal traps were set up during three entomological surveys and 3347 tsetse flies were collected, dissected and 1903 midguts collected. DNA was extracted from midguts and specific primers were used to identify Trypanosoma congolense forest and savannah. All Trypanosoma congolense forest positive samples were characterized with seven microsatellite markers. RESULTS: Microscopic examination revealed 25 (1.31%) mid-gut infections with trypanosomes while the PCR method identified 120 (6.3%) infections due to Trypanosoma congolense: 94 (78.33%) Trypanosoma congolense forest and 28 (21.77%) Trypanosoma congolense savannah. The trypanosome infection rates varied significantly between villages and years of capture. Menji recorded the highest infection rate (15.11%); and samples captured in 2009 were more infected (14.33%). The microsatellite markers revealed a genetic variability between Trypanosoma congolense forest populations of Fontem villages and 6.38% of mixed infections due to different genotypes of T. congolense "forest type". CONCLUSION: Our data on the population genetics play in favor of a clonal reproduction of this parasite. The microsatellite markers used here showed a low genetic differentiation and an absence of sub-structuration (FST <= 0.0003) between Trypanosoma congolense forest populations of Fontem villages. However, the high FST value (FST >= 0.3911) between samples of the Democratic Republic of Congo and those of Fontem villages indicates low migration rates between trypanosomes of these subpopulations. PMID- 25142137 TI - [The transfer of psychiatry-narratives, termini and cross-cultural psychiatry in Japan]. AB - This article is based on German and Japanese sources and shows how around 1900 European psychiatric concepts and practices embedded themselves into emerging scientific Japanese discourses. The article argues that now forgotten German Japanese exchanges in the field of psychiatric pathology, together with the historical development of psychiatric care, were central mechanisms for the establishment of a distinctly psychiatric discourse in Japan priot to its broad institutionalization. Three discursive strategies were key: Japanese and German experts from a range of medical fields reinvented a body of traditions loosely related to actual pre-modern cultural practices; they engaged in comparative evaluations of psychiatric conditions; and, through the simple but effective transformation of specific concepts and termini at the margins of European psychiatry, these experts contributed to the transfer not only of a psychiatric discourse but also affected the power relations on a national and international scale as European psychiatry permeated into new territory, namely the Japanese landscape of emerging modern scientific disciplines. PMID- 25142139 TI - Enhanced gene disruption by programmable nucleases delivered by a minicircle vector. AB - Targeted genetic modification using programmable nucleases such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) is of great value in biomedical research, medicine and biotechnology. Minicircle vectors, which lack extraneous bacterial sequences, have several advantages over conventional plasmids for transgene delivery. Here, for the first time, we delivered programmable nucleases into human cells using transient transfection of a minicircle vector and compared the results with those obtained using a conventional plasmid. Surrogate reporter assays and T7 endonuclease analyses revealed that cells in the minicircle vector group displayed significantly higher mutation frequencies at the target sites than those in the conventional plasmid group. Quantitative PCR and reverse transcription-PCR showed higher vector copy number and programmable nuclease transcript levels, respectively, in 293T cells after minicircle versus conventional plasmid vector transfection. In addition, tryphan blue staining and flow cytometry after annexin V and propidium iodide staining showed that cell viability was also significantly higher in the minicircle group than in the conventional plasmid group. Taken together, our results show that gene disruption using minicircle vector-mediated delivery of ZFNs and TALENs is a more efficient, safer and less toxic method than using a conventional plasmid, and indicate that the minicircle vector could serve as an advanced delivery method for programmable nucleases. PMID- 25142138 TI - Overexpression of X-Linked Inhibitor of Apoptotic Protein (XIAP) reduces age related neuronal degeneration in the mouse cochlea. AB - Previously, we showed that age-related hearing loss (AHL) was delayed in C57BL6 mice overexpressing X-Linked Inhibitor of Apoptotic Protein (XIAP), and the delayed AHL was associated with attenuated hair cell (HC) loss in XIAP overexpressing mice. Similar to other reports, the HC loss in aged mice was restricted to the basal turn in this previous study, and occurred slightly at the apical end of the cochlea, showing considerably less spread than the frequency region of hearing loss. In the present study, we examined whether and how AHL is related to the degeneration of neuronal innervation of the cochlea and whether the overexpression of XIAP exerts a protective effect against age-related degeneration in both afferent and efferent cochlear neurites. In contrast to HC loss, degeneration of both afferent and efferent neurites spread to the middle turns of the cochlea. Moreover, XIAP-overexpressing mice lost fewer HC afferent dendrites and efferent axons, as well as fewer spiral ganglion neurons between 3 and 14 months of age in comparison with wild-type littermates. The results suggest that age-related degeneration of cochlear neurites may be independent of HC loss. Further, the inhibition of apoptosis by XIAP appears to reduce degeneration of both afferent and efferent cochlear neurites. PMID- 25142140 TI - High and prolonged sulfamidase secretion by the liver of MPS-IIIA mice following hydrodynamic tail vein delivery of antibiotic-free pFAR4 plasmid vector. AB - Mucopolysaccharidosis type IIIA (MPS-IIIA) or Sanfilippo A syndrome is a lysosomal storage genetic disease that results from the deficiency of the N sulfoglucosamine sulfohydrolase (SGSH) protein, a sulfamidase required for the degradation of heparan sulfate glycosaminoglycans (GAGs). The accumulation of these macromolecules leads to somatic organ pathologies, severe neurodegeneration and death. To assess a novel gene therapy approach based on prolonged secretion of the missing enzyme by the liver, mediated by hydrodynamic gene delivery, we first compared a kanamycin and an antibiotic-free expression plasmid vector, called pFAR4. Thanks to the reduced vector size, pFAR4 derivatives containing either a ubiquitous or a liver-specific promoter mediated a higher reporter gene expression level than the control plasmid. Hydrodynamic delivery of SGSH-encoding pFAR4 into MPS-IIIA diseased mice led to high serum levels of sulfamidase protein that was efficiently taken up by neighboring organs, as shown by the correction of GAG accumulation. A similar reduction in GAG content was also observed in the brain, at early stages of the disease. Thus, this study contributes to the effort towards the development of novel biosafe non-viral gene vectors for therapeutic protein expression in the liver, and represents a first step towards an alternative gene therapy approach for the MPS-IIIA disease. PMID- 25142141 TI - Special issue on headache and sleep. PMID- 25142142 TI - Migraine and restless legs syndrome: a systematic review. AB - BACKGROUND: Restless legs syndrome (RLS) is increasingly being reported as a comorbidity of migraine. METHODS: We conducted a systematic review and meta analysis of studies investigating RLS in headache/migraine and vice versa. We calculated the prevalence and 95% confidence intervals (CI) of RLS in headache/migraine, of headache/migraine in RLS and controls, and odds ratios (ORs) of the association between the conditions. We then determined pooled effect estimates for the associations. RESULTS: We identified 24 studies. RLS prevalence in migraine ranged from 8.7% to 39.0% with no apparent differences based on gender and aura status. Prevalence among controls was compatible with the literature. Migraine prevalence in RLS ranged from 15.1% to 62.6%. We did not pool prevalence data because of high unexplained heterogeneity. High heterogeneity with respect to the association between any migraine and RLS could be explained by study design. Pooled analyses showed substantially higher effect estimates in case-control studies (pooled OR = 4.19, 95% CI 3.07-5.71; I (2) = 0.0%) than in cohort studies (pooled OR = 1.22, 95% CI 1.14-1.30; I (2) = 0.0%). CONCLUSION: Our results support the concept of RLS as an important comorbidity of migraine. However, the degree of association appears to be strongly determined by study design. Potential effects by gender and aura status and the role of RLS in other headache disorders remain unclear. PMID- 25142143 TI - Disposal of iNKT cell deficiency and an increase in expression of SLAM signaling factors characterizes sarcoidosis remission: a 4-year longitudinal study. AB - BACKGROUND: Invariant NKT (iNKT) cells are regulatory lymphocytes that may be important in disorders with increased Th1 responses. We utilized a 4-year longitudinal observational study of iNKT cells and SLAM signaling pathway factors, which are important for iNKT development in patients with newly diagnosed sarcoidosis. METHODS: Detailed clinical, functional, and radiographic evaluation and determination of iNKT peripheral blood cell counts and expression of SLAM signaling factors was carried out at presentation and after 3 months, 1 year, and 4 years of disease follow-up in 29 patients with pulmonary sarcoidosis. At presentation, we also evaluated the frequencies of pulmonary BALF iNKT cells. We also included 37 control subjects. RESULTS: We demonstrated a marked deficiency of blood and lung iNKT cells and decreased expression of SLAM signaling factors in patients with newly diagnosed sarcoidosis. During 4 years of disease follow-up, there was a significant increase in blood iNKT cell numbers and in expression of SLAM signaling factors, mainly SLAMF1, SLAMF6, and FYN. This increase clearly correlated with improvement in patients' clinical symptoms. At the 4-year endpoint, the disease had gone into remission in the great majority of patients and thus also iNKT cell deficiency. Moreover, at the 4-year endpoint iNKT level reached the iNKT level of the control subjects. CONCLUSIONS: Our longitudinal study showed that a disposal of iNKT deficiency in parallel with an increase in expression of SLAM signaling factors characterizes the clinical remission of sarcoidosis. PMID- 25142144 TI - A three-microRNA signature predicts responses to platinum-based doublet chemotherapy in patients with lung adenocarcinoma. AB - PURPOSE: To examine the clinical utility of intratumor microRNAs (miRNA) as a biomarker for predicting responses to platinum-based doublet chemotherapy in patients with recurring lung adenocarcinoma (LADC). EXPERIMENTAL DESIGN: The expression of miRNAs was examined in LADC tissues surgically resected from patients treated with platinum-based doublet chemotherapy at the time of LADC recurrence. Microarray-based screening of 904 miRNAs followed by quantitative reverse transcription-PCR-based verification in 40 test cohort samples, including 16 (40.0%) responders, was performed to identify miRNAs that are differentially expressed in chemotherapy responders and nonresponders. Differential expression was confirmed in a validation cohort (n = 63 samples), including 18 (28.6%) responders. An miRNA signature that predicted responses to platinum-based doublet chemotherapy was identified and its accuracy was examined by principal component and support vector machine analyses. Genotype data for the TP53-Arg72Pro polymorphism, which is associated with responses to platinum-based doublet chemotherapy, were subsequently incorporated into the prediction analysis. RESULTS: A signature comprising three miRNAs (miR1290, miR196b, and miR135a*) enabled the prediction of a chemotherapeutic response (rather than progression free and overall survival) with high accuracy in both the test and validation cohorts (82.5% and 77.8%). Examination of the latter was performed using miRNAs extracted from archived formalin-fixed paraffin-embedded tissues. Combining this miRNA signature with the TP53-Arg72Pro polymorphism genotype marginally improved the predictive power. CONCLUSION: The three-miRNA signature in surgically resected primary LADC tissues may by clinically useful for predicting responsiveness to platinum-based doublet chemotherapy in patients with LADC recurrence. PMID- 25142147 TI - IL-18: a new player in immunotherapy for age-related macular degeneration? AB - Recent evidence suggests that the pro-inflammatory cytokine IL-18 may have utility as an anti-angiogenic agent in the eye. Numerous laboratories, including our own have demonstrated the ability of murine IL-18 to prevent neovascularization in the retina, choroid and cornea in pathological scenarios. Here, we summarize the potential use of IL-18 as an immunotherapy for wet age related macular degeneration treatment, describing past and recent findings pertaining to its biological function in the eye. PMID- 25142145 TI - Curing mice with large tumors by locally delivering combinations of immunomodulatory antibodies. AB - PURPOSE: Immunomodulatory mAbs can treat cancer, but cures are rare except for small tumors. Our objective was to explore whether the therapeutic window increases by combining mAbs with different modes of action and injecting them into tumors. EXPERIMENTAL DESIGN: Combinations of mAbs to CD137/PD-1/CTLA-4 or CD137/PD-1/CTLA-4/CD19 were administrated intratumorally to mice with syngeneic tumors (B16 and SW1 melanoma, TC1 lung carcinoma), including tumors with a mean surface of approximately 80 mm(2). Survival and tumor growth were assessed. Immunologic responses were evaluated using flow cytometry and qRT-PCR. RESULTS: More than 50% of tumor-bearing mice had complete regression and long-term survival after tumor injection with mAbs recognizing CD137/PD-1/CTLA-4/CD19 with similar responses in three models. Intratumoral injection was more efficacious than intraperitoneal injection in causing rejection also of untreated tumors in the same mice. The three-mAb combination could also induce regression, but was less efficacious. There were few side effects, and therapy-resistant tumors were not observed. Transplanted tumor cells rapidly caused a Th2 response with increased CD19 cells. Successful therapy shifted this response to the Th1 phenotype with decreased CD19 cells and increased numbers of long-term memory CD8 effector cells and T cells making IFNgamma and TNFalpha. CONCLUSIONS: Intratumoral injection of mAbs recognizing CD137/PD-1/CTLA-4/CD19 can eradicate established tumors and reverse a Th2 response with tumor-associated CD19 cells to Th1 immunity, whereas a combination lacking anti-CD19 is less effective. There are several human cancers for which a similar approach may provide clinical benefit. PMID- 25142146 TI - Antitumor activity of the ERK inhibitor SCH772984 [corrected] against BRAF mutant, NRAS mutant and wild-type melanoma. AB - BACKGROUND: In melanoma, dysregulation of the MAPK pathway, usually via BRAF(V600) or NRAS(Q61) somatic mutations, leads to constitutive ERK signaling. While BRAF inhibitors are initially effective for BRAF-mutant melanoma, no FDA approved targeted therapies exist for BRAF-inhibitor-resistant BRAF(V600), NRAS mutant, or wild-type melanoma. METHODS: The 50% inhibitory concentration (IC50) of SCH772984, a novel inhibitor of ERK1/2, was determined in a panel of 50 melanoma cell lines. Effects on MAPK and AKT signaling by western blotting and cell cycle by flow cytometry were determined. RESULTS: Sensitivity fell into three groups: sensitive, 50% inhibitory concentration (IC50) < 1 MUM; intermediately sensitive, IC50 1-2 MUM; and resistant, >2 MUM. Fifteen of 21 (71%) BRAF mutants, including 4 with innate vemurafenib resistance, were sensitive to SCH772984. All three (100%) BRAF/NRAS double mutants, 11 of 14 (78%) NRAS mutants and 5 of 7 (71%) wild-type melanomas were sensitive. Among BRAF(V600) mutants with in vitro acquired resistance to vemurafenib, those with MAPK pathway reactivation as the mechanism of resistance were sensitive to SCH772984. SCH772984 caused G1 arrest and induced apoptosis. CONCLUSIONS: Combining vemurafenib and SCH722984 in BRAF mutant melanoma was synergistic in a majority of cell lines and significantly delayed the onset of acquired resistance in long term in vitro assays. Therefore, SCH772984 may be clinically applicable as a treatment for non-BRAF mutant melanoma or in BRAF-mutant melanoma with innate or acquired resistance, alone or in combination with BRAF inhibitors. PMID- 25142148 TI - The accountability for reasonableness approach to guide priority setting in health systems within limited resources--findings from action research at district level in Kenya, Tanzania, and Zambia. AB - BACKGROUND: Priority-setting decisions are based on an important, but not sufficient set of values and thus lead to disagreement on priorities. Accountability for Reasonableness (AFR) is an ethics-based approach to a legitimate and fair priority-setting process that builds upon four conditions: relevance, publicity, appeals, and enforcement, which facilitate agreement on priority-setting decisions and gain support for their implementation. This paper focuses on the assessment of AFR within the project REsponse to ACcountable priority setting for Trust in health systems (REACT). METHODS: This intervention study applied an action research methodology to assess implementation of AFR in one district in Kenya, Tanzania, and Zambia, respectively. The assessments focused on selected disease, program, and managerial areas. An implementing action research team of core health team members and supporting researchers was formed to implement, and continually assess and improve the application of the four conditions. Researchers evaluated the intervention using qualitative and quantitative data collection and analysis methods. RESULTS: The values underlying the AFR approach were in all three districts well-aligned with general values expressed by both service providers and community representatives. There was some variation in the interpretations and actual use of the AFR in the decision-making processes in the three districts, and its effect ranged from an increase in awareness of the importance of fairness to a broadened engagement of health team members and other stakeholders in priority setting and other decision-making processes. CONCLUSIONS: District stakeholders were able to take greater charge of closing the gap between nationally set planning and the local realities and demands of the served communities within the limited resources at hand. This study thus indicates that the operationalization of the four broadly defined and linked conditions is both possible and seems to be responding to an actual demand. This provides arguments for the continued application and further assessment of the potential of AFR in supporting priority-setting and other decision-making processes in health systems to achieve better agreed and more sustainable health improvements linked to a mutual democratic learning with potential wider implications. PMID- 25142149 TI - Immunological aspects of radiotherapy. PMID- 25142150 TI - Familiar trajectories facilitate the interpretation of physical forces when intercepting a moving target. AB - Familiarity with the visual environment affects our expectations about the objects in a scene, aiding in recognition and interaction. Here we tested whether the familiarity with the specific trajectory followed by a moving target facilitates the interpretation of the effects of underlying physical forces. Participants intercepted a target sliding down either an inclined plane or a tautochrone. Gravity accelerated the target by the same amount in both cases, but the inclined plane represented a familiar trajectory whereas the tautochrone was unfamiliar to the participants. In separate sessions, the gravity field was consistent with either natural gravity or artificial reversed gravity. Target motion was occluded from view over the last segment. We found that the responses in the session with unnatural forces were systematically delayed relative to those with natural forces, but only for the inclined plane. The time shift is consistent with a bias for natural gravity, in so far as it reflects an a priori expectation that a target not affected by natural forces will arrive later than one accelerated downwards by gravity. Instead, we did not find any significant time shift with unnatural forces in the case of the tautochrone. We argue that interception of a moving target relies on the integration of the high-level cue of trajectory familiarity with low-level cues related to target kinematics. PMID- 25142151 TI - Internal models of upper limb prosthesis users when grasping and lifting a fragile object with their prosthetic limb. AB - Internal models allow unimpaired individuals to appropriately scale grip force when grasping and lifting familiar objects. In prosthesis users, the internal model must adapt to the characteristics of the prosthetic devices and reduced sensory feedback. We studied the internal models of 11 amputees and eight unimpaired controls when grasping and lifting a fragile object. When the object was modified from a rigid to fragile state, both subject groups adapted appropriately by significantly reducing grasp force on the first trial with the fragile object compared to the rigid object (p < 0.020). There was a wide range of performance skill illustrated by amputee subjects when lifting the fragile object in 10 repeated trials. One subject, using a voluntary close device, never broke the object, four subjects broke the fragile device on every attempt and seven others failed on their initial attempts, but improved over the repeated trials. Amputees decreased their grip forces 51 +/- 7 % from the first to the last trial (p < 0.001), indicating a practice effect. However, amputees used much higher levels of force than controls throughout the testing (p < 0.015). Amputees with better performance on the Box and Blocks test used lower grip force levels (p = 0.006) and had more successful lifts of the fragile object (p = 0.002). In summary, amputees do employ internal models when picking up objects; however, the accuracy of these models is poor and grip force modulation is significantly impaired. Further studies could examine the alternative sensory modalities and training parameters that best promote internal model formation. PMID- 25142152 TI - The early release of actions by loud sounds in muscles with distinct connectivity. AB - The presentation of an unexpected and loud auditory stimulus (LAS) during action preparation can trigger movement onset much sooner than normal. Recent research has attributed this effect to the activation of reticulospinal connections to the target muscles. To our knowledge, no studies have investigated the effects of LAS presentation in tasks requiring the simultaneous activation of muscles with different connectivity to motor areas of the brain. Here, we sought to establish the importance of muscle connectivity by asking participants to contract the orbicularis oris and abductor pollicis brevis muscles simultaneously. A LAS was randomly presented at 200 ms prior to the expected time of movement onset in an anticipatory timing task. We show that muscles controlled via bulbar connections to reticular formation can be triggered early by sound as much as muscles with spinal connections to the reticular formation. PMID- 25142153 TI - Online monitoring of concentration and dynamics of volatile fatty acids in anaerobic digestion processes with mid-infrared spectroscopy. AB - An ATR-MIR-FTIR spectrometer was integrated into a laboratory scale anaerobic digestion setup. Automatically, a sludge sample from the digester was transferred to a measurement cell; an IR spectrum was recorded and evaluated by chemometric models to estimate the concentration of the individual volatile fatty acids (VFA). The calibration set included semi-artificial samples spiked with known concentrations of the VFA as well as original samples from a continuous fermentation. High-performance liquid chromatography (HPLC) was used as a reference analysis of the samples. The models were optimized for a low root mean square error of prediction (RMSEP). R(2) for acetic acid, propionic acid, isobutyric acid, butyric acid, valeric acid, and isovaleric acid were 0.94, 0.88, 0.83, 0.75, 0.59, and 0.90, respectively. The accuracy of the models was validated in a second experiment. Considering the complex and heterogeneous sludge composition and the chemical similarity of VFA, absolute concentration and dynamic (increasing and decreasing concentration of VFA) was predicted well for acetic, propionic, isobutyric, and isovaleric acid (in their respective concentration range); Butyric acid could not be detected. The installed setup was able to gather and measure native samples from the digester (every 2 h) automatically over a period of 6 months without problems of clogging or biofouling. The instant and continuous analysis of the concentration of the VFA made it possible to evaluate the current bioprocess status and adjust the organic loading rate accordingly. PMID- 25142154 TI - Optimizing promoters and secretory signal sequences for producing ethanol from inulin by recombinant Saccharomyces cerevisiae carrying Kluyveromyces marxianus inulinase. AB - Inulin is a polyfructan that is abundant in plants such as Jerusalem artichoke, chicory and dahlia. Inulinase can easily hydrolyze inulin to fructose, which is consumed by microorganisms. Generally, Saccharomyces cerevisiae, an industrial workhorse strain for bioethanol production, is known for not having inulinase activity. The inulinase gene from Kluyveromyces marxianus (KmINU), with the ability of converting inulin to fructose, was introduced into S. cerevisiae D452 2. The inulinase gene was fused to three different types of promoter (GPD, PGK1, truncated HXT7) and secretory signal sequence (KmINU, MFalpha1, SUC2) to generate nine expression cassettes. The inulin fermentation performance of the nine transformants containing different promoter and signal sequence combinations for inulinase production were compared to select an optimized expression system for efficient inulin fermentation. Among the nine inulinase-producing transformants, the S. cerevisiae carrying the PGK1 promoter and MFalpha1 signal sequence (S. cerevisiae D452-2/p426PM) showed not only the highest specific KmINU activity, but also the best inulin fermentation capability. Finally, a batch fermentation of the selected S. cerevisiae D452-2/p426PM in a bioreactor with 188.2 g/L inulin was performed to produce 80.2 g/L ethanol with 0.43 g ethanol/g inulin of ethanol yield and 1.22 g/L h of ethanol productivity. PMID- 25142155 TI - Involvement of patients with lung and gynecological cancer and their relatives in psychosocial cancer rehabilitation: a narrative review. AB - INTRODUCTION: Getting cancer is stressful for most patients and their relatives, and research has shown that psychosocial support is needed. Still, cancer care fails to appropriately address psychosocial problems associated with cancer. Research on this topic is often seen from the perspective of either the patient or the relative, even though it is suggested that psychosocial support is beneficial for the patient and the relative as a pair. Furthermore, research on the need for psychosocial support rarely involves patients with gynecological and lung cancer and their relatives, even though they often suffer from isolation and stigmatization. The aim of this review was therefore to summarize knowledge about psychosocial support with regard to individual needs, involvement of significant others, and providers of psychosocial support focusing on this specific population. METHOD: A narrative review procedure was chosen. This method is a specific kind of review, which summarizes, explains, and interprets evidence on a selected topic. The review process was structured according to typical scholarly articles with attention to the search and review process. RESULTS: A total of 16 studies were included in the review. The studies were divided into two main categories: (1) studies focusing on needs for psychosocial support; and (2) studies focusing on interventions. The needs studies were analyzed, and three themes emerged: the needs of the patient and the significant other across the cancer trajectory; the needs of the significant other as a carer; and needs and ongoing and tailored support. The intervention studies were directed toward the patient and the relative, the patient, or the relative. Five interventions comprising various forms of support that were purely supportive and were carried out by healthcare professionals were identified. CONCLUSION: There were overlaps between the needs of the patient and the relative, but there were also distinctive characteristics of the needs in the two groups. The needs varied during the cancer trajectory, and we therefore recommend that support be offered continuously. It was also evident that the relatives should be involved in the patients' care and that the involvement was beneficial for both the patient and the relative. PMID- 25142156 TI - Investigating patient perspectives on medical returns and buying medicines online in two communities in Melbourne, Australia: results from a qualitative study. AB - AIMS: By going online or overseas, patients can purchase a range of prescription and over-the-counter drugs and complementary and alternative medicine (CAM), without prescription and without input from a qualified health professional. Such practices raise questions about medicine safety and how and why patients choose to procure medicines using such methods. The aim of this paper is to examine two unconventional types of medicine procurement-medical returns and purchasing medicines online-from the patient perspective. METHODS: Data are drawn from a large qualitative study examining health-seeking practices among Indian Australians (28) and Anglo-Australians (30) living with depression in Melbourne, Australia. Semi-structured face-to-face interviews were undertaken. Thematic analysis was performed. FINDINGS: A total of 23 (39.6 %) participants reported having obtained medicines either through the internet or via medical returns. Indian-Australians sourced medicines from India while Anglo-Australians purchased CAM products from domestic and international e-pharmacies. Neither group encountered any difficulties in the medicines entering Australia. Cost and convenience were the main reasons for buying medicines online but dissatisfaction with Australian health services also influenced why Indian-Australians sought medicines from India. Nearly all participants reported benefits from consuming these medicines; only one person reported adverse effects. CONCLUSION: The increased availability of medicines transnationally and patients' preparedness to procure these medicines from a range of sources raise important issues for the safe use of medicines. Further research is needed to understand how patients forge their own transnational therapeutic regimes, understand and manage their levels of risk in relation to safe medicine use and what points of intervention might be most effective to promote safe medicine use. PMID- 25142157 TI - Relating gene expression evolution with CpG content changes. AB - BACKGROUND: Previous studies have shown that CpG dinucleotides are enriched in a subset of promoters and the CpG content of promoters is positively correlated with gene expression levels. But the relationship between divergence of CpG content and gene expression evolution has not been investigated. Here we calculate the normalized CpG (nCpG) content in DNA regions around transcription start site (TSS) and transcription terminal site (TTS) of genes in nine organisms, and relate them with expression levels measured by RNA-seq. RESULTS: The nCpG content of TSS shows a bimodal distribution in all organisms except platypus, whereas the nCpG content of TTS only has a single peak. When the nCpG contents are compared between different organisms, we observe a different evolution pattern between TSS and TTS: compared with TTS, TSS exhibits a faster divergence rate between closely related species but are more conserved between distant species. More importantly, we demonstrate the link between gene expression evolution and nCpG content changes: up-/down- regulation of genes in an organism is accompanied by the nCpG content increase/decrease in their TSS and TTS proximal regions. CONCLUSIONS: Our results suggest that gene expression changes between different organisms are correlated with the alterations in normalized CpG contents of promoters. Our analyses provide evidences for the impact of nCpG content on gene expression evolution. PMID- 25142158 TI - The hydroxyectoine gene cluster of the non-halophilic acidophile Acidiphilium cryptum. AB - Acidiphilium cryptum is an acidophilic, heterotrophic alpha-Proteobacterium which thrives in acidic, metal-rich environments (e.g. acid mine drainage). Recently, an ectABCDask gene cluster for biosynthesis of the compatible solutes ectoine and hydroxyectoine was detected in the genome sequence of A. cryptum JF-5. We were able to demonstrate that the type strain A. cryptum DSM 2389(T) is capable of synthesizing the compatible solute hydroxyectoine in response to moderate osmotic stress caused by sodium chloride and aluminium sulphate, respectively. Furthermore, we used the A. cryptum JF-5 sequence to amplify the ectABCDask gene cluster from strain DSM 2389(T) and achieved heterologous expression of the gene cluster in Escherichia coli. Hence, we could for the first time prove metabolic functionality of the genes responsible for hydroxyectoine biosynthesis in the acidophile A. cryptum. In addition, we present information on specific enzyme activity of A. cryptum DSM 2389(T) ectoine synthase (EctC) in vitro. In contrast to EctCs from halophilic microorganisms, the A. cryptum enzyme exhibits a higher isoelectric point, thus a lower acidity, and has maximum specific activity in the absence of sodium chloride. PMID- 25142159 TI - Characterization of the frhAGB-encoding hydrogenase from a non-methanogenic hyperthermophilic archaeon. AB - The F420-reducing hydrogenase has been known as a key enzyme in methanogenesis. Its homologs have been identified in non-methanogenic hyperthermophilic archaea, including Thermococcus onnurineus NA1, but neither physiological function nor biochemical properties have been reported to date. The enzyme of T. onnurineus NA1 was distinguished from those of other methanogens and the members of the family Desulfurobacteriaceae with respect to the phylogenetic distribution of the alpha and beta subunits, organization of frhAGB genes and conservation of F420 coordinating residues. RT-qPCR and Western blot analyses revealed frhA gene is not silent but is expressed in T. onnurineus NA1 grown in the presence of sulfur, carbon monoxide, or formate. The trimeric enzyme complex was purified to homogeneity via affinity chromatography from T. onnurineus NA1 and exhibited catalytic activity toward the electron acceptors such as viologens and flavins but not the deazaflavin coenzyme F420. This is the first biochemical study on the function of the frhAGB-encoding enzyme from a non-methanogenic archaea. PMID- 25142160 TI - A depletion layer in polymer solutions at an interface oscillating at the subnano to submicrometer scale. AB - The mobility of segments of the polymer mesh in a solution determines the dynamic response of the depletion layer (DL) to mechanical stimuli. This phenomenon can be used to vastly decrease the local viscosity experienced by any device performing periodic motion at the nano- and microscale in complex liquids. We refined the vibrating quartz tuning fork (QTF) method to probe the viscosity of model aqueous solutions of polyethylene glycol, covering a broad range of molecular weights (3 kDa to 1 MDa) and QTF oscillation amplitudes (50 pm to 100 nm). For semidilute solutions of PEGs of high molecular weight, we found a drop of local viscosity, up to two orders of magnitude below the bulk value. We propose a simple explanation based on the motion of the depletion layer, strongly supported by rheometry and dynamic light scattering results. We show that it is possible to directly probe the viscosity of the DL and increase its thickness far above the equilibrium value. The key role is played by the rate of relaxation of the entangled system. The relevance of this paradigm ranges from the basic research on dynamics of entangled systems to design of energy-efficient nanomachines operating in a crowded environment. PMID- 25142161 TI - Physiological role of taurine--from organism to organelle. AB - Taurine is often referred to as a semi-essential amino acid as newborn mammals have a limited ability to synthesize taurine and have to rely on dietary supply. Taurine is not thought to be incorporated into proteins as no aminoacyl tRNA synthetase has yet been identified and is not oxidized in mammalian cells. However, taurine contributes significantly to the cellular pool of organic osmolytes and has accordingly been acknowledged for its role in cell volume restoration following osmotic perturbation. This review describes taurine homeostasis in cells and organelles with emphasis on taurine biophysics/membrane dynamics, regulation of transport proteins involved in active taurine uptake and passive taurine release as well as physiological processes, for example, development, lung function, mitochondrial function, antioxidative defence and apoptosis which seem to be affected by a shift in the expression of the taurine transporters and/or the cellular taurine content. PMID- 25142162 TI - Deep sequencing of KIT, MET, PIK3CA, and PTEN hotspots in papillary thyroid carcinomas with distant metastases. PMID- 25142163 TI - Identification of a potential novel type of influenza virus in Bovine in China. AB - Bovine influenza virus was first identified in the USA in 2013, and the virus represents a potential novel type of influenza viruses. However, the distribution and evolution of the virus remain unknown. We conducted a pilot survey of bovine influenza virus in China, and identified three bovine influenza viruses which are highly homogenous to the ones identified in the USA, suggesting that the bovine influenza virus likely circulates widely and evolves slowly in the world. PMID- 25142164 TI - Characterization of the biological properties and complete genome sequence analysis of a cattle-derived rabies virus isolate from the Guangxi province of southern China. AB - In this study, a street rabies virus isolate, GXHXN, was obtained from the brain of one rabid cattle in Guangxi province of southern China. To characterize the biological properties of GXHXN, we first evaluated its pathogenicity using 4-week old adult mice. GXHXN was highly pathogenic with a short incubation period and course of disease. Its LD50 of 10(-6.86)/mL is significantly higher than the LD50 of 10(-5.19)/mL of GXN119, a dog-derived rabies virus isolate. It also displayed a higher neurotropism index than the rRC-HL strain. However, the relative neurotropism index of GXHXN was slightly lower than that of GXN119. Analyzing antigenicity using anti-N and anti-G monoclonal antibodies (MAbs), all tested anti-N MAbs reacted similarly to GXHXN, CVS, and rRC-HL, but the reaction of anti N MAbs to GXHXN was slightly different from GXN119. Moreover, 2/11 tested anti-G mAbs showed weaker reactivity to GXHXN than rRC-HL, whereas 4/11 showed stronger reactivity to GXHXN than CVS and GXN119, indicating that the structures of G might differ. In order to understand its genetic variation and evolution, the complete GXHXN genome sequence was determined and compared with the known 12 isolates from other mammals. A total of 42 nucleotide substitutions were found in the full-length genome, including 15 non-synonymous mutations. The G gene accounts for the highest nucleotide substitution rate of 0.70 % in ORF and an amino acid substitution rate of 0.95 %. Phylogenetic trees based on the complete genome sequence as well as the N and G gene sequences from 37 known rabies isolates from various mammals demonstrated that the GXHXN is closely related to the BJ2011E isolate from a horse in Beijing, the WH11 isolate from a donkey in Hubei, and isolates from dogs in the Fujian and Zhejiang provinces. These findings will be helpful in exploring the molecular mechanisms underlying interspecies transmission and the genetic variation of the rabies virus in different mammal species. PMID- 25142165 TI - Circulating Lp(a):LDL complexes contain LDL molecules proportionate to Lp(a) size and bind to galectin-1: a possible route for LDL entry into cells. AB - The molecular mechanism of vascular pathology mediated by circulating lipoprotein(a) [Lp(a)] remains unknown. We examined the role of two distinguishing features of Lp(a) viz non-covalent complex formation with a low density lipoprotein (LDL) and heavy glycosylation as determinants of binding of this lipoprotein and its LDL complex to cell-surface receptors. LDL isolated from the Lp(a):LDL complex, free LDL and oxidized LDL were equally efficient in forming a reconstituted complex with pure Lp(a). Complexed LDL in healthy individuals was equal in oxidation status to free LDL. The number of LDL molecules associated with each Lp(a) molecule (LDL index) in plasma samples increased steadily with Lp(a) size (correlation coefficient r = 0.834). Complex reconstituted from purified plasma Lp(a) and LDL maintained the same LDL index as plasma in accordance with Lp(a) size. Consequently, the percentage of complex free Lp(a) in the plasma decreased sharply with Lp(a) size (r = -0.887). Although O-glycosylation measured in terms of lectin binding increased with Lp(a) size, the LDL index increased significantly faster than O-glycosylation among Lp(a) phenotypes of different plasma samples. Complexes with varying stoichiometry existed in the same plasma. Extra LDL complex molecules were not recognized by LDL receptors on human macrophages or rat cardiac fibroblasts indicating attachment to Lp(a) involved LDL receptor-binding sites. However, unlike free LDL complex LDL could attach through Lp(a) to immobilized form of galectin-1, a lectin ubiquitous on mammalian cells. Results suggest that phenotype-dependence of the physiological and pathological functions of Lp(a) may operate through differential LDL-carrier activity. PMID- 25142166 TI - Altered expression of genes associated with telomere maintenance and cell function of human vascular endothelial cell at elevated temperature. AB - The pathophysiological alterations of vascular endothelial cells induced by heat were studied. Human umbilical venous endothelial cells were cultured for 1 day at three different temperatures (37, 39, and 42 degrees C). The telomere lengths, the expressions of proteins associated with telomere length maintenance, apoptosis, heat shock, and vascular function were analyzed. The cell growth was not suppressed at 39 degrees C but suppressed at 42 degrees C. The mean telomere length did not change, whereas the telomere length distribution altered at 42 degrees C. Long telomere decreased and middle-sized telomere increased in the telomere length distribution at 42 degrees C. The telomerase activity did not show any heat-associated alterations. However, of the components of telomerase, telomerase reverse transcriptase was up-regulated along temperature elevation. In contrast, the expression level of RNA component TERC did not altered. Among the analyzed apoptosis-associated proteins, p21 was down-regulated and phosphorylated p53 was up-regulated. Heat shock proteins and NO synthase were up-regulated at 42 degrees C. These results suggested that induced growth suppression or cell senescence was induced by strong heat stress rather than mild one predominantly in cells bearing long telomeres with p53 activation, and simultaneously activated some telomere-associated factors, heat shock proteins, and NO synthesis probably for heat-resistant cell survival. PMID- 25142167 TI - Clinicopathologic features and outcome of mycophenolate-induced colitis in renal transplant recipients. AB - Reports on the clinical course of mycophenolic acid (MPA)-related colitis in kidney transplant recipients are scarce. This study aimed at assessing MPA related colitis incidence, risk factors, and progression after kidney transplantation. All kidney transplant patients taking MPA who had colonic biopsies for persistent chronic diarrhea, between 2000 and 2012, at the Kidney Transplantation Unit of Botucatu Medical School Hospital, Brazil, were included. Cytomegalovirus (CMV) immunohistochemistry was performed in all biopsy specimens. Data on presenting symptoms, medications, immunosuppressive drugs, colonoscopic findings, and follow-up were obtained. Of 580 kidney transplant patients on MPA, 34 underwent colonoscopy. Colonoscopic findings were associated with MPA usage in 16 patients. The most frequent histologic patterns were non-specific colitis (31.3%), inflammatory bowel disease (IBD)-like colitis (25%), normal/near normal (18.8%), graft-versus-host disease-like (18.8%), and ischemia-like colitis (12.5%). All patients had persistent acute diarrhea and weight loss. Six of the 16 MPA-related diarrhea patients (37.5%) showed acute dehydration requiring hospitalization. Diarrhea resolved when MPA was switched to sirolimus (50%), discontinued (18.75%), switched to azathioprine (12.5%), or reduced by 50% (18.75%). No graft loss occurred. Four patients died during the study period. Late-onset MPA was more frequent, and no correlation with MPA dose or formulation was found. PMID- 25142168 TI - GRG profiles: Professor Ignazio Marino. PMID- 25142169 TI - Correlation of Helicobacter pylori genotypes with gastric histopathology in the central region of a South-European country. AB - BACKGROUND: Outcome of Helicobacter pylori (H. pylori) infection results from interaction of multiple variables including host, environmental and bacterial associated virulence factors. AIM: This study aimed to investigate the correlation of cagA, cagE, vacA, iceA and babA2 genotypes with gastric histopathology and disease phenotype in the central region of a South-European country. METHODS: This prospective study involved 148 infected patients (110 female; mean age 43.5 +/- 13.4 years) submitted to endoscopy with corpus and antrum biopsies. H. pylori was cultured and DNA extracted from the isolates. Genotypes were determined by PCR. Histopathological features were graded according to the updated Sydney system and OLGA/OLGIM classification. Only patients with single H. pylori genotypes and complete histopathological results were included. RESULTS: Antrum samples presented higher degrees of atrophy, intestinal metaplasia, chronic inflammation and neutrophil activity. Genotype distribution was as follows: cagA-31.8 %; cagE-45.9 %; vacA s1a-24.3 %; vacA s1b 19.6 %; vacA s1c-0.7 %; vacA s2-55.4 %; vacA m1-20.9 %; vacA m2-79.1 %; vacA s1m1 18.9 %; vacA s1m2-25.7 %; vacA s2m1-2 %; vacA s2m2-53.4 %; iceA1-33.8 %; iceA2 66.2 %; babA2-12.2 %. CagA genotype was significantly associated with higher degrees of intestinal metaplasia, neutrophil activity, chronic inflammation and OLGIM stages. BabA2 was linked with higher H. pylori density. Strains with vacA s1m1 or vacA s1m1 + cagA positive genotypes had a significant association with peptic ulcer and vacA s2m2 with iron-deficient anemia. CONCLUSIONS: cagA, vacA s1m1 and babA2 genotypes are relatively rare in the central region of Portugal. cagA-positive strains are correlated with more severe histopathological modifications. This gene is commonly associated with vacA s1m1, and such isolates are frequently found in patients with peptic ulcer. PMID- 25142170 TI - Dietary requirement for serum-derived bovine immunoglobulins in the clinical management of patients with enteropathy. AB - A variety of human disease conditions are associated with chronic intestinal disorders or enteropathies that are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Such disruptions in the homeostasis of the gastrointestinal (GI) tract can lead to symptoms of abdominal pain and discomfort, bloating, abnormal bowel function, and malabsorption of nutrients. While significant advances have been made in understanding the factors that influence the complex and fragile balance between the gut microbiota, intestinal epithelial cell integrity, and the underlying immune system, effective therapies for restoring intestinal balance during enteropathy are still not available. Numerous studies have demonstrated the ability of oral immunoglobulins to improve weight gain, support gut barrier function, and reduce the severity of enteropathy in animals. More recently, studies in humans provide evidence that serum-derived bovine immunoglobulin/protein isolate is safe and improves nutritional status and GI symptoms in patients with enteropathy associated with irritable bowel syndrome or infection with the human immunodeficiency virus. This review summarizes studies showing the impact of enteropathy on nutritional status and how specially formulated bovine immunoglobulins may help restore intestinal homeostasis and nutritional status in patients with specific enteropathies. Such protein preparations may provide distinct nutritional support required for the dietary management of patients who, because of therapeutic or chronic medical needs, have limited or impaired capacity to digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or other special medically determined nutrient requirements that cannot be satisfied by changes to the normal diet alone. PMID- 25142171 TI - Use of cffDNA to avoid administration of anti-D to pregnant women when the fetus is RhD-negative: implementation in the NHS. AB - OBJECTIVE: To determine whether a policy of offering cffDNA testing to all RhD negative women at about 16 weeks' gestation to avoid anti-D administration when the fetus is RhD-negative could be implemented successfully in the NHS without additional funding. DESIGN: Prospectively planned observational service implementation pilot and notes audit. SETTING: Three maternity services in the South West of England. POPULATION: All RhD-negative women in a 6-month period. METHODS: Prospective, intervention, cross-sectional observational study, using pre-intervention data as controls. MAIN OUTCOME MEASURES: Proportion of suitable women who offered and accepted the test. Accuracy of the cffDNA result as assessed by cord blood group result. Fall in anti-D doses administered. RESULTS: 529 samples were received; three were unsuitable. The results were reported as RhD-positive (n = 278), RhD-negative (n = 185) or inconclusive, treat as positive (n = 63). Cord blood results were available in 502 (95%) and the only incorrect result was one case of a false positive (cffDNA reported as positive, cord blood negative - and so given anti-D unnecessarily). The notes audit showed that women who declined this service were correctly managed and that anti-D was not given when the fetus was predicted to be RhD-negative. The total use of anti-D doses fell by about 29% which equated to about 35% of RhD-negative women not receiving anti-D in their pregnancy unnecessarily. CONCLUSIONS: We recommend this service is extended to all UK NHS services. PMID- 25142172 TI - Rice responses to rising temperatures--challenges, perspectives and future directions. AB - Phenotypic plasticity in overcoming heat stress-induced damage across hot tropical rice-growing regions is predominantly governed by relative humidity. Expression of transpiration cooling, an effective heat-avoiding mechanism, will diminish with the transition from fully flooded paddies to water-saving technologies, such as direct-seeded and aerobic rice cultivation, thus further aggravating stress damage. This change can potentially introduce greater sensitivity to previously unaffected developmental stages such as floral meristem (panicle) initiation and spikelet differentiation, and further intensify vulnerability at the known sensitive gametogenesis and flowering stages. More than the mean temperature rise, increased variability and a more rapid increase in nighttime temperature compared with the daytime maximum present a greater challenge. This review addresses (1) the importance of vapour pressure deficit under fully flooded paddies and increased vulnerability of rice production to heat stress or intermittent occurrence of combined heat and drought stress under emerging water-saving rice technologies; (2) the major disconnect with high night temperature response between field and controlled environments in terms of spikelet sterility; (3) highlights the most important mechanisms that affect key grain quality parameters, such as chalk formation under heat stress; and finally (4), we model and estimate heat stress-induced spikelet sterility taking South Asia as a case study. PMID- 25142173 TI - Selenium modulates mercury uptake and distribution in rice (Oryza sativa L.), in correlation with mercury species and exposure level. AB - Rice cultured in Hg- and/or Se-contaminated fields is an important food source of human Hg/Se intake. There are elevated Hg and Se levels in the soil of the Wanshan District, Guizhou Province. Here we attempted to explore how a Hg antagonist, Se, modulates the absorption and accumulation of inorganic mercury (IHg) and methylmercury (MeHg) in rice. The effects of Se on the content and transportation of Hg in hydroponic and soil cultured rice plants were examined. The results show that IHg mainly accumulated in the rice roots, but some also accumulated in the rice grain. In comparison to IHg, MeHg can be concentrated in the rice grain, and the proportion of MeHg in the rice grain may account for above 40% of the total Hg. Se can protect against Hg phytotoxicity in rice and inhibit IHg accumulation in rice tissues, but was not remarkable for MeHg at a low dosage exposure level in this study. These discrepancies imply mechanistic differences between IHg and MeHg absorption and accumulation in rice. This study illustrates that Se plays an important role in modulating Hg uptake, transportation and accumulation in rice. Therefore, Se is considered to be a naturally existing element that effectively reduces Hg accumulation in rice, which may have significant implications for food safety. PMID- 25142175 TI - Characterization of squamous cell carcinomas of the head and neck using methods of spatial statistics. AB - In the present study, 53 cases of squamous cell carcinomas of the head and neck were characterized by a quantitative histological texture analysis based on principles of spatial statistics. A planar tessellation of the epithelial tumour component was generated by a skeletonization algorithm. The size distribution of the virtual cells of this planar tessellation, and the size distribution of the profiles of the tumour cell nuclei were estimated in terms of area and boundary length. The intensity, the reduced second moment function (K-function) and the pair correlation function of the point process of the centroids of the profiles of the tumour cell nuclei were also estimated. For both purposes, it is necessary to correct for edge effects, which we consider in this paper in some detail. Specifically, the point patterns of the tumour cell nuclei were considered as realizations of a point process, where the points exist only in the epithelial tumour component (the permitted phase) and not in the stroma (the forbidden phase). The methods allow to characterize each individual tumour by a series of summary statistics. The total set of cases was then partitioned into two groups: 19 cases without lymph node metastases (pN0), and 34 nodal positive cases (pN1 or pN2). Statistical analysis showed no significant differences between the intensities, the mean K-functions and the mean pair correlation functions of the tumour cell nucleus profiles of the two groups. However, there were some significant differences between the sizes of the virtual cells and of the nucleus profiles of the nodal negative cases as compared to the nodal positive cases. In a logistic regression analysis, one of the quantitative nuclear size variables (mean nuclear area) was found to be a significant predictor of lymph node metastasis, in addition to tumour stage. The study shows the potential of methods of spatial statistics for objective quantitative grading of squamous cell carcinomas of the head and neck, and provides an example for modelling histological point patterns as realizations of planar point processes occupying a reference phase which is only a partial component of the total tissue. PMID- 25142174 TI - Expansive open-door laminoplasty secured with titanium miniplates is a good surgical method for multiple-level cervical stenosis. AB - BACKGROUND: Laminoplasty is an effective procedure for treating cervical spondylotic myelopathy (CSM). Little information is available regarding the surgical outcomes of expansive open-door laminoplasty (EOLP) when securing with titanium miniplates without bone grafting. This study is aimed to elucidate the efficacy of and problems associated with EOLP secured with titanium miniplates without bone grafting, thereby enhancing future surgical outcomes. METHODS: This is a retrospective study. The study participants comprised 104 patients who underwent cervical EOLP secured with titanium miniplates without bone graft for CSM treatment between August 2005 and March 2011. The clinical results were evaluated based on the Japanese Orthopedic Association (JOA) and Nurick scores. The radiographic outcomes were determined based on plain film and magnetic resonance imaging findings, which were assessed and compared. RESULTS: Lateral cervical spine X-rays exhibited improvement in the Pavlov ratio of the spinal canal at 1 day postoperation, and this ratio did not change at 1 year postoperation. The mean cervical curvature from C2 to C7 decreased 0.21 degrees +/- 10.09 degrees and the mean cervical range of motion was deteriorated by 35% at 12 months (P < 0.05). The Nurick score improved from 3.19 +/- 1.06 to 0.92 +/- 1.32 (P < 0.05). The mean JOA recovery rate was 75% +/- 21.1% at 1 year. The mean level of postoperative neck pain at 3 months was 3.09 +/- 2.31, as determined using the visual analogue scale (VAS). Increased age, concomitant thoracolumbar stenosis, depression disorder, and preexisting myelomalacia negatively affected the JOA recovery rate (P < 0.05). A decreased preoperative Nurick score and superior sensory function in the upper extremities were powerful predictors of an enhanced JOA recovery rate. The postoperative complications involved hematoma formation 0.9%, reversible C5 nerve palsy 2.8%, and moderate to severe neck pain (VAS >= 4) 42%. No cases of lamina closure or collapse were observed. CONCLUSION: EOLP secured with titanium miniplates without bone grafting is a safe and effective surgical method for treating most patients with CSM. PMID- 25142176 TI - Photosynthesis research for sustainability: keys to produce clean energy. PMID- 25142177 TI - The effects of life stress and neural learning signals on fluid intelligence. AB - Fluid intelligence (fluid IQ), defined as the capacity for rapid problem solving and behavioral adaptation, is known to be modulated by learning and experience. Both stressful life events (SLES) and neural correlates of learning [specifically, a key mediator of adaptive learning in the brain, namely the ventral striatal representation of prediction errors (PE)] have been shown to be associated with individual differences in fluid IQ. Here, we examine the interaction between adaptive learning signals (using a well-characterized probabilistic reversal learning task in combination with fMRI) and SLES on fluid IQ measures. We find that the correlation between ventral striatal BOLD PE and fluid IQ, which we have previously reported, is quantitatively modulated by the amount of reported SLES. Thus, after experiencing adversity, basic neuronal learning signatures appear to align more closely with a general measure of flexible learning (fluid IQ), a finding complementing studies on the effects of acute stress on learning. The results suggest that an understanding of the neurobiological correlates of trait variables like fluid IQ needs to take socioemotional influences such as chronic stress into account. PMID- 25142178 TI - Feasibility of amylin imaging in pancreatic islets with beta-amyloid imaging probes. AB - Islet amyloid deposition composed of amylin aggregates is regarded as one of the hallmarks of type 2 diabetes mellitus (T2DM). For the diagnosis of T2DM, several nuclear medical imaging probes have been developed. However, there have been no reports regarding the development of imaging probes targeting amylin. In this report, we investigated the feasibility of amylin imaging using [(125)I]IPBF as one of the model compounds of beta-amyloid (Abeta) imaging probes. In in vitro experiments, [(125)I]IPBF exhibited high binding affinity for amylin aggregates (Kd = 8.31 nM). Moreover, autoradiographic images showed that [(125)I]IPBF specifically bound to islet amyloid composed of amylin. These results suggest the potential application of Abeta imaging probes to amylin imaging. In addition, [(125)I]IPBF is one of the promising lead compounds for amylin imaging, and further structural optimization based on [(125)I]IPBF may lead to useful tracers for the in vivo imaging of islet amyloids in the pancreas. PMID- 25142179 TI - Modified high-density lipoproteins by artificial sweetener, aspartame, and saccharin, showed loss of anti-atherosclerotic activity and toxicity in zebrafish. AB - Safety concerns have been raised regarding the association of chronic consumption of artificial sweeteners (ASs) with metabolic disorders, especially in the heart and brain. There has been no information on the in vivo physiological effects of AS consumption in lipoprotein metabolism. High-dosage treatment (final 25, 50, and 100 mM) with AS (aspartame, acesulfame K, and saccharin) to human high density lipoprotein (HDL) induced loss of antioxidant ability along with elevated atherogenic effects. Aspartame-treated HDL3 (final 100 mM) almost all disappeared due to putative proteolytic degradation. Aspartame- and saccharin-treated HDL3 showed more enhanced cholesteryl ester transfer activity, while their antioxidant ability was disappeared. Microinjection of the modified HDL3 exacerbated the inflammatory death in zebrafish embryos in the presence of oxLDL. These results show that AS treatment impaired the beneficial functions of HDL, resulting in loss of antioxidant and anti-atherogenic activities. These results suggest that aspartame and saccharin could be toxic to the human circulation system as well as embryonic development via impairment of lipoprotein function. PMID- 25142180 TI - Correction of Discretization Errors Simulated at Supply Wells. AB - Many hydrogeology problems require predictions of hydraulic heads in a supply well. In most cases, the regional hydraulic response to groundwater withdrawal is best approximated using a numerical model; however, simulated hydraulic heads at supply wells are subject to errors associated with model discretization and well loss. An approach for correcting the simulated head at a pumping node is described here. The approach corrects for errors associated with model discretization and can incorporate the user's knowledge of well loss. The approach is model independent, can be applied to finite difference or finite element models, and allows the numerical model to remain somewhat coarsely discretized and therefore numerically efficient. Because the correction is implemented external to the numerical model, one important benefit of this approach is that a response matrix, reduced model approach can be supported even when nonlinear well loss is considered. PMID- 25142181 TI - On the origin of the spontaneous formation of nanocavities in hexagonal bronzes (W,V)O3. AB - Hexagonal (W,V)O3-x oxides of high thermal stability have been synthesized hydrothermally through the intermediate products Nax(W,V)O3.zH2O and (NH4)0.33 x(W,V)O3-y. The obtained crystals show nanostructured surface via the formation of a dense population of polyhedral nanocavities self-distributed along particular crystallographic directions. Nanocavities present a regular size that ranges from 5 to 10 nm in both length and width. The synthesis process involves a significant topotactic relationship between the as-synthesized product and the desired final product and this relationship is suggested as the origin of the observed surface nanostructure. The comparison of our results with observations in different solids has allowed us to suggest that the formation of nanocavities is an extensive spontaneous process when materials are obtained by the chemical reactions of solids leading to products with defined crystallographic orientation with respect to the original compound. The characterization provides evidence regarding the potential relevance of nanocavities in the functional properties of the resulting solids. PMID- 25142182 TI - Distal-proximal skin temperature gradient prior to sleep onset in infants for clinical use. AB - BACKGROUND: The objective of this study was to explore the possibility of using distal-proximal skin temperature gradient (DPG) to predict sleep-onset latency of night-time sleep for infants at home. METHODS: Foot (for distal) and abdominal (for proximal) skin temperature during sleep onset in healthy infants, aged 4-9 months, was continuously recorded using a temperature logger at home. Sleep-onset latency during each study night was defined as the interval from lights-off to sleep onset, determined on actigraphy. Association of DPG profile after lights off with sleep-onset latency on the study nights was evaluated. RESULTS: Data for 43 nights from 28 infants were available for analysis. With regard to low DPG (< 2.5 degrees C) at lights-off, >60% of infants fell asleep within 30 min if DPG was increased to >=-2.5 degrees C within 15 min after lights-off. If DPG remained at <-2.5 degrees C at 15 min after lights-off, however, only 20% of infants fell asleep within 30 min. In addition, if infants were still awake at 15 min after lights-off and the DPG at that time was <-2.5 degrees C, they were not likely to quickly fall asleep (predictive value was 0.875). CONCLUSIONS: Increase in DPG by 15 min after lights-off is a key determinant for sleep-onset latency. PMID- 25142183 TI - Determination of dabigatran, rivaroxaban and apixaban by ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) and coagulation assays for therapy monitoring of novel direct oral anticoagulants. AB - BACKGROUND: Three novel direct oral anticoagulants (DOACs) have recently been registered by the Food and Drug Administration and European Medicines Agency Commission: dabigatran, rivaroxaban, and apixaban. To quantify DOACs in plasma, various dedicated coagulation assays have been developed. OBJECTIVE: To develop and validate a reference ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method and to evaluate the analytical performance of several coagulation assays for quantification of dabigatran, rivaroxaban, and apixaban. METHODS: The developed UPLC-MS/MS method was validated by determination of precision, accuracy, specificity, matrix effects, lower limits of detection, carry-over, recovery, stability, and robustness. The following coagulation assays were evaluated for accuracy and precision: laboratory-developed (LD) diluted thrombin time (dTT), Hemoclot dTT, Pefakit PiCT, ECA, Liquid anti-Xa, Biophen Heparin (LRT), and Biophen DiXal anti-Xa. Agreement between the various coagulation assays and UPLC-MS/MS was determined with random samples from patients using dabigatran or rivaroxaban. RESULTS: The UPLC-MS/MS method was shown to be accurate, precise, sensitive, stable, and robust. The dabigatran coagulation assay showing the best precision, accuracy and agreement with the UPLC-MS/MS method was the LD dTT test. For rivaroxaban, the anti-factor Xa assays were superior to the PiCT-Xa assay with regard to precision, accuracy, and agreement with the reference method. For apixaban, the Liquid anti-Xa assay was superior to the PiCT-Xa assay. CONCLUSIONS: Statistically significant differences were observed between the various coagulation assays as compared with the UPLC MS/MS reference method. It is currently unknown whether these differences are clinically relevant. When DOACs are quantified with coagulation assays, comparison with a reference method as part of proficiency testing is therefore pivotal. PMID- 25142184 TI - CXCL16 haplotypes in patients with human carotid atherosclerosis: preliminary results. AB - AIM: Chemokine CXC ligand 16 (CXCL16) has chemoattractive, adhesive and scavenging properties and may play a role in the formation of atherosclerotic lesions. However, studies of CXCL16 polymorphisms in patients with atherosclerosis are scarce. The missense polymorphisms I123T and A181V are potentially important factors in the regulation of presentation and shedding of the CXCL16 chemokine domain. The aim of this study was to analyze the association between I123T and A181V polymorphism haplotypes and the accumulation of carotid plaque as well as the effect of the haplotype on the CXCL16 mRNA expression in carotid plaques in patients with advanced atherosclerosis. Additionally, we performed a bioinformatic prediction analysis of the impact of CXCL16 protein sequence variation on CXCL16-CXCR6 interactions and analyzed the soluble CXCL16 plasma levels according to the CXCL16 haplotype. METHODS: This study evaluated a total of 733 participants, including 283 controls and 450 patients with carotid atherosclerosis (CA) undergoing endarterectomy. Analyses of the polymorphisms and the gene expression were performed using real-time PCR. The soluble CXCL16 levels were measured with ELISA. RESULTS: The missense allele haplotype, T123V181, was found to be significantly and independently associated with the occurrence of CA plaque (OR=1.27;1.02-1.57, p=0.03). This haplotype was predicted to significantly change the CXCL16-CXCR6 interaction, compared to I123A181. Neither the CXCL16 mRNA expression in the human plaques nor the soluble CXCL16 plasma levels differed according to the haplotype. CONCLUSIONS: These results indicate that the CXCL16 T123V181 haplotype is a moderate genetic risk factor for the development of carotid plaque. Further functional and replication studies are needed to clarify the mechanisms by which this combination of alleles promotes advanced CA and validate its impact on disease progression. PMID- 25142185 TI - Metabolite profiling and peptidoglycan analysis of transient cell wall-deficient bacteria in a new Escherichia coli model system. AB - Many bacteria are able to assume a transient cell wall-deficient (or L-form) state under favourable osmotic conditions. Cell wall stress such as exposure to beta-lactam antibiotics can enforce the transition to and maintenance of this state. L-forms actively proliferate and can return to the walled state upon removal of the inducing agent. We have adopted Escherichia coli as a model system for the controlled transition to and reversion from the L-form state, and have studied these dynamics with genetics, cell biology and 'omics' technologies. As such, a transposon mutagenesis screen underscored the requirement for the Rcs phosphorelay and colanic acid synthesis, while proteomics show only little differences between rods and L-forms. In contrast, metabolome comparison reveals the high abundance of lysophospholipids and phospholipids with unsaturated or cyclopropanized fatty acids in E. coli L-forms. This increase of membrane lipids associated with increased membrane fluidity may facilitate proliferation through bud formation. Visualization of the residual peptidoglycan with a fluorescently labelled peptidoglycan binding protein indicates de novo cell wall synthesis and a role for septal peptidoglycan synthesis during bud constriction. The DD carboxypeptidases PBP5 and PBP6 are threefold and fourfold upregulated in L forms, indicating a specific role for regulation of crosslinking during L-form proliferation. PMID- 25142186 TI - Uncovering the information core in recommender systems. AB - With the rapid growth of the Internet and overwhelming amount of information that people are confronted with, recommender systems have been developed to effectively support users' decision-making process in online systems. So far, much attention has been paid to designing new recommendation algorithms and improving existent ones. However, few works considered the different contributions from different users to the performance of a recommender system. Such studies can help us improve the recommendation efficiency by excluding irrelevant users. In this paper, we argue that in each online system there exists a group of core users who carry most of the information for recommendation. With them, the recommender systems can already generate satisfactory recommendation. Our core user extraction method enables the recommender systems to achieve 90% of the accuracy of the top-L recommendation by taking only 20% of the users into account. A detailed investigation reveals that these core users are not necessarily the large-degree users. Moreover, they tend to select high quality objects and their selections are well diversified. PMID- 25142187 TI - Purification, molecular cloning and functional characterization of flavonoid C glucosyltransferases from Fagopyrum esculentum M. (buckwheat) cotyledon. AB - C-Glycosides are characterized by their C-C bonds in which the anomeric carbon of the sugar moieties is directly bound to the carbon atom of aglycon. C-Glycosides are remarkably stable, as their C-C bonds are resistant to glycosidase or acid hydrolysis. A variety of plant species are known to accumulate C glycosylflavonoids; however, the genes encoding for enzymes that catalyze C glycosylation of flavonoids have been identified only from Oryza sativa (rice) and Zea mays (maize), and have not been identified from dicot plants. In this study, we identified the C-glucosyltransferase gene from the dicot plant Fagopyrum esculentum M. (buckwheat). We purified two isozymes from buckwheat seedlings that catalyze C-glucosylation of 2-hydroxyflavanones, which are expressed specifically in the cotyledon during seed germination. Following purification we isolated the cDNA corresponding to each isozyme [FeCGTa (UGT708C1) and FeCGTb (UGT708C2)]. When expressed in Escherichia coli, both proteins demonstrated C-glucosylation activity towards 2-hydroxyflavanones, dihydrochalcone, trihydroxyacetophenones and other related compounds with chemical structures similar to 2',4',6'-trihydroxyacetophenone. Molecular phylogenetic analysis of plant glycosyltransferases shows that flavonoid C glycosyltransferases form a different clade with other functionally analyzed plant glycosyltransferases. PMID- 25142188 TI - Regional media coverage influences the public's negative attitudes to policy implementation success in Sweden. AB - BACKGROUND: One central aspect of health literacy is knowledge of patients' rights. Being an important source of information about health and health care, the media may influence health literacy and act as a policy implementer. OBJECTIVE: To investigate whether regional news media coverage in Sweden is linked to (i) the public's awareness and knowledge of a patient's rights policy, the waiting-time guarantee and (ii) the public's attitudes to how the guarantee's time limits are met, that is, implementation success. DESIGN AND DATA: Three types of data are used. First, a national telephone survey of the public's awareness, knowledge and attitudes; second, media coverage information from digital media monitoring; and third, official waiting-time statistics. Bivariate and multivariate regression analyses are performed with the 21 Swedish county councils/regions as a base. RESULTS: In the county councils/regions, non awareness ranged from 1 to 15% and knowledge from 47 to 67%. There are relatively large differences between population groups. The amount of regional media coverage shows no significant correlation to the level of awareness and knowledge. There is, however, a significant correlation to both positive and negative attitudes; the latter remains after controlling for actual waiting times. DISCUSSION AND CONCLUSIONS: At the national level, the media function as a policy implementer, being the primary source of information. At the regional level, the media are part of the political communication, reporting more extensively in county councils/regions where the population holds negative views towards the achievement in implementing the guarantee. We conclude that Swedish authorities should develop its communication strategies to bridge health literacy inequalities. PMID- 25142189 TI - A randomized trial of prophylactic palifermin on gastrointestinal toxicity after intensive induction therapy for acute myeloid leukaemia. AB - Gastrointestinal toxicity, including oral mucositis, is a frequent complication of intensive combination chemotherapy for acute myeloid leukaemia (AML) and contributes substantially to treatment-related mortality. We conducted a placebo controlled randomized trial to evaluate the efficacy of palifermin (keratinocyte growth factor), given at 60 MUg/kg per daily IV for 3 d before and after chemotherapy, for mucosal protection in adult patients with previously untreated AML receiving induction therapy with idarubicin, high-dose cytarabine and etoposide. Among 155 randomized patients, there was no statistically significant difference in the rate of grade 3 and 4 oral mucositis (primary study endpoint) between the two treatment arms (three in palifermin arm (4%), 8 in placebo arm (10%; P = 0.21); however, when considering the severity of oral mucositis (World Health Organization grade 0-4), there was evidence of reduced rates of higher grades of oral mucositis in the palifermin arm (P = 0.0007, test for trend). There was a statistically significantly lower rate of grades 3 and 4 gastrointestinal adverse events in the palifermin arm (21% vs. 44% in placebo arm; P = 0.003), mainly due to a reduction in severe diarrhoea (8% palifermin, 26% placebo; P = 0.01). Palifermin has activity as a mucosal protectant in AML patients receiving intensive chemotherapy. This trial is registered at ACTRN012605000095662. PMID- 25142190 TI - Effects of acute administration of mazindol on brain energy metabolism in adult mice. AB - OBJECTIVES: Mazindol is a sympathomimetic amine, widely used as an anorectic agent in the treatment of obesity. This drug causes psychostimulant effects because of its pharmacological profile similar to amphetamine, acting like a monoamine reuptake inhibitor. However, the mechanisms underlying the action of mazindol are still not clearly understood. METHODS: Swiss mice received a single acute administration of mazindol (0.25, 1.25 and 2.5 mg/kg, ip) or saline. After 2 h, the animals were killed by decapitation; the brain was removed and used for the evaluation of activities of mitochondrial respiratory chain complexes, Krebs cycle enzymes and creatine kinase. RESULTS: Acute administration of mazindol decreased complex I activity only in the hippocampus. Complex IV activity was increased in the cerebellum (2.5 mg/kg) and cerebral cortex (0.25 mg/kg). Citrate synthase activity was increased in the cerebellum (1.25 mg/kg) and cerebral cortex (1.25 mg/kg), and creatine kinase activity was increased in the cerebellum (1.25 mg/kg). CONCLUSION: We suggest that the inhibition of complex I in the hippocampus only and activation of complex IV, citrate synthase and creatine kinase occurs because of a stimulus effect of mazindol in the central nervous system, which causes a direct impairment on energy metabolism. PMID- 25142191 TI - Psychometric analysis of the Melancholia Scale in trials with non-pharmacological augmentation of patients with therapy-resistant depression. AB - OBJECTIVE: The Melancholia Scale (MES) consists of the psychic core items of the Hamilton Depression Scale (HAM-D6) (depressed mood, interests, psychic anxiety, general somatic, guilt feelings, and psychomotor retardation) and the neuropsychiatric items of the Cronholm-Ottossen Depression Scale. Patients resistant to anti-depressant medication (therapy-resistant depression) have participated in our trials with non-pharmacological augmentation. On the basis of these trials, we have evaluated to what extent the neuropsychiatric subscale of the MES (concentration difficulties, fatigability, emotional introversion, sleep problems, and decreased verbal communication) is a measure of severity of apathia when compared with the HAM-D6 subscale of the MES. METHODS: We have focused on rating sessions at baseline (week 0) and after 2 and 4 weeks of therapy in four clinical trials on therapy-resistant depression with the following augmentations: electroconvulsive therapy, bright light therapy, transcranial magnetic stimulation or pulsed electromagnetic fields, and wake therapy. The item response theory model constructed by Mokken has been used as the psychometric validation of unidimensionality. For the numerical evaluation of transferability, we have tested item ranks across the rating weeks. RESULTS: In the Mokken analysis, the coefficient of homogeneity was above 0.40 for both the HAM-D subscale and the apathia subscale at week 4. The numerical transferability across the weeks was statistically significant (p < 0.05) for both subscales. CONCLUSION: The apathia subscale is a unidimensional scale with acceptable transferability for the measurement of treatment-resistant symptoms, analogue to the psychic core subscale (HAM-D6). PMID- 25142192 TI - Long-term effects of ageing and ovariectomy on aversive and recognition memory and DNA damage in the hippocampus of female rats. AB - OBJECTIVE: This study investigated the influence of ageing - in particular the decrease of gonadal hormone levels during the ageing process - on the memory and the levels of DNA damage in the hippocampus of female rats. METHODS: Three groups of female Wistar rats were investigated: Group I consisted of non-ovariectomised, adult animals (6 months old); Group II consisted of non-ovariectomised, aged animals (18 months old); and Group III consisted of ovariectomised, aged animals (18 months old). The memory of the animals in these groups was examined via novel object recognition and inhibitory avoidance tests. The hippocampus tissue samples of all animals were obtained via biopsy and used to quantify the DNA damage using a Comet Assay. RESULTS: According to our findings, the process of ageing results in a change during the behavioural tests. To prevent genotoxic damage to the hippocampus caused by the ageing process, lowered hormone levels seem to be part of a protective biochemical mechanism in the body of rats. Animals that were previously submitted to an ovariectomy adapted better to these lower levels of hormones. CONCLUSION: Our results indicate that ovariectomy can provide beneficial long-term effects on the memory. However, this could be specific to the kind of memory examined, as the aversive memory deficits caused by ageing were not affected by ovariectomy. PMID- 25142193 TI - Interleukin-6 inhibits voltage-gated sodium channel activity of cultured rat spinal cord neurons. AB - OBJECTIVE: Interleukin-6 (IL-6) is a pleiotropic proinflammatory cytokine that plays a key role in the injuries and diseases of the central nervous system (CNS). A voltage-gated Na+ channel (VGSC) is essential for the excitability and electrical properties of the neurons. However, there is still limited information on the role of IL-6 in voltage-gated sodium channels. Our study aimed to investigate the effects of IL-6 on Na+ currents in cultured spinal-cord neurons. METHODS: VGSC currents were activated and recorded using whole-cell patch-clamp technique in the cultured rat spinal cord neurons. The effects of IL-6 concentration and exposure duration were examined. To determine whether any change in the number of channels in the plasma membrane can inhibit IL-6 on VGSC currents, we examined the expression of alpha1A (SCN1alpha) subunit mRNA level and protein level in the neurons before and after IL-6 induction using real-time polymerase chain reaction. RESULTS: We verified that IL-6, through a receptor mediated mechanism, suppressed Na+ currents in a time- and dose-dependent manner, but did not alter the voltage-dependent activation and inactivation. Gp130 was involved in this inhibition. Furthermore, the spike amplitude was also inhibited by IL-6 in the doses that decreased the Na+ currents. CONCLUSION: VGSC currents are significantly inhibited by IL-6. Our findings reveal that the potential neuroprotection of IL-6 may result from the inhibitory effects on VGSC currents. PMID- 25142194 TI - omega-3 and major depression: a review. AB - BACKGROUND: The World Health Organization estimates that major depression affects about 350 million people all over the world and reports this disorder as the major contributor to the global burden of diseases. Despite the well-defined symptomatology, major depression is a heterogeneous psychiatric disorder whose pathophysiology is not clearly established. Although several treatments are available, most depressed patients do not achieve the complete remission of symptoms. Factors linked to the persistence of the disorder have been investigated, particularly those related to the way of life. Moreover, it has been suggested that nutritional aspects may influence its development. Among them, a diet rich in omega-3 has been associated with a reduced risk of major depression, although its deficiency is associated with depressive disorders. METHODS: This review provides a general view about evidences of the use of omega 3 in major depression cases. RESULTS: Several studies have demonstrated beneficial effects of omega-3 in the prevention and treatment of major depression. However, not all the results have shown significant statistical benefits. CONCLUSIONS: More studies are necessary to clarify detailed mechanisms of the antidepressant effects of omega-3 and may explain the source of contradictions in results published until the moment. PMID- 25142195 TI - Neurosyphilis in the mixed urban-rural community of the Netherlands. AB - OBJECTIVE: Neurosyphilis is caused by dissemination into the central nervous system of Treponema pallidum. Although the incidence of syphilis in the Netherlands has declined since the mid-1980s, syphilis has re-emerged, mainly in the urban centres. It is not known whether this also holds true for neurosyphilis. METHODS: The epidemiology of neurosyphilis in Dutch general hospitals in the period 1999-2010 was studied in a retrospective cohort study. Data from the Dutch sexually transmitted infection (STI) clinics were used to analyse the number of patients diagnosed with syphilis in this period. RESULTS: An incidence of neurosyphilis of 0.47 per 100 000 adults was calculated, corresponding with about 60 new cases per year. This incidence was higher in the western (urbanised) part of the Netherlands, as compared with the more rural areas (0.6 and 0.4, respectively). The number of patients diagnosed with syphilis in STI clinics increased from 150 to 700 cases in 2004 and decreased to 500 new cases in 2010. The sex ratio was in favour of men, yielding a percentage of 90% of the syphilis cases and of 75% of the neurosyphilitic cases. The incidence of neurosyphilis was highest in men aged 35-65 years, and in women aged 75 years and above. The most frequently reported clinical manifestation of neurosyphilis was tabes dorsalis. In this study, 15% of the patients were HIV seropositive. CONCLUSION: The incidence of neurosyphilis in a mixed urban-rural community such as the Netherlands is comparable to that in other European countries. Most patients are young, urban and men, and given the frequent atypical manifestations of the disease reintroduction of screening for neurosyphilis has to be considered. PMID- 25142198 TI - Intrateam coverage is common, intrateam handoffs are not. PMID- 25142197 TI - Evaluating effective dose of dexmedetomidine: onset time of drug is critical. PMID- 25142199 TI - Ergonomic comparison of laparoscopic hand instruments in a single site surgery simulator with novices. AB - BACKGROUND: Single-site surgery improves cosmesis but increases procedural difficulty. Enhanced instruments could improve procedural efficiency leading to better patient outcomes. MATERIAL AND METHODS: One pair of non-articulating (straight) and two different pairs of articulating laparoscopic instruments were evaluated using a peg-transfer surgical task simulator by premedical college students. The instruments were comparatively tested using task performance measures, ergonomic measures, and participant questionnaires. RESULTS: The straight instrument produced significantly higher task performance scores and lower task times compared to both articulating instruments (p < 0.05). The straight instrument required less muscle activation and less wrist deviation than the articulating instruments to perform the same task. Participants rated the straight instrument significantly easier to use and less difficult to complete the task than with either articulating instrument (p < 0.05 for both). CONCLUSIONS: This exploratory study suggests that novices have difficulty using articulating instruments and perform better using straight laparoscopic instruments when first attempting LESS surgical tasks. Although a study with post graduate medical trainees is needed to confirm these results, trainees should initially practice LESS with non-articulating instruments to gain proficiency at basic laparoscopic tasks. Additionally, redesigning articulating instruments to specifically address the spatial constraints and learning curve of LESS may also improve trainee performance and instrument usability. PMID- 25142196 TI - Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial. AB - IMPORTANCE: Antidepressant medication (ADM) is efficacious in the treatment of depression, but not all patients achieve remission and fewer still achieve recovery with ADM alone. OBJECTIVE: To determine the effects of combining cognitive therapy (CT) with ADM vs ADM alone on remission and recovery in major depressive disorder (MDD). DESIGN, SETTING, AND PARTICIPANTS: A total of 452 adult outpatients with chronic or recurrent MDD participated in a trial conducted in research clinics at 3 university medical centers in the United States. The patients were randomly assigned to ADM treatment alone or CT combined with ADM treatment. Treatment was continued for up to 42 months until recovery was achieved. INTERVENTIONS: Antidepressant medication with or without CT. MAIN OUTCOMES AND MEASURES: Blind evaluations of recovery with a modified version of the 17-item Hamilton Rating Scale for Depression and the Longitudinal Interval Follow-up Evaluation. RESULTS: Combined treatment enhanced the rate of recovery vs treatment with ADM alone (72.6% vs 62.5%; t451 = 2.45; P = .01; hazard ratio [HR], 1.33; 95% CI, 1.06-1.68; number needed to treat [NNT], 10; 95% CI, 5-72). This effect was conditioned on interactions with severity (t451 = 1.97; P = .05; NNT, 5) and chronicity (chi2 = 7.46; P = .02; NNT, 6) such that the advantage for combined treatment was limited to patients with severe, nonchronic MDD (81.3% vs 51.7%; n = 146; t145 = 3.96; P = .001; HR, 2.34; 95% CI, 1.54-3.57; NNT, 3; 95% CI, 2-5). Fewer patients dropped out of combined treatment vs ADM treatment alone (18.9% vs 26.8%; t451 = -2.04; P = .04; HR, 0.66; 95% CI, 0.45-0.98). Remission rates did not differ significantly either as a main effect of treatment or as an interaction with severity or chronicity. Patients with comorbid Axis II disorders took longer to recover than did patients without comorbid Axis II disorders regardless of the condition (P = .01). Patients who received combined treatment reported fewer serious adverse events than did patients who received ADMs alone (49 vs 71; P = .02), largely because they experienced less time in an MDD episode. CONCLUSIONS AND RELEVANCE: Cognitive therapy combined with ADM treatment enhances the rates of recovery from MDD relative to ADMs alone, with the effect limited to patients with severe, nonchronic depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00057577. PMID- 25142200 TI - Gripping during climbing of arboreal snakes may be safe but not economical. AB - On the steep surfaces that are common in arboreal environments, many types of animals without claws or adhesive structures must use muscular force to generate sufficient normal force to prevent slipping and climb successfully. Unlike many limbed arboreal animals that have discrete gripping regions on the feet, the elongate bodies of snakes allow for considerable modulation of both the size and orientation of the gripping region. We quantified the gripping forces of snakes climbing a vertical cylinder to determine the extent to which their force production favoured economy or safety. Our sample included four boid species and one colubrid. Nearly all of the gripping forces that we observed for each snake exceeded our estimate of the minimum required, and snakes commonly produced more than three times the normal force required to support their body weight. This suggests that a large safety factor to avoid slipping and falling is more important than locomotor economy. PMID- 25142201 TI - How many and which ant species are being accidentally moved around the world? AB - Human transportation facilitates the dispersal of exotic ants, but few studies have quantified the magnitude and geography of these movements. We used several non-parametric indices to estimate the number of species successfully introduced to or established in new regions. We also compared their source biogeographic realms to assess the importance of geographical origin in determining the likelihood of establishment after introduction. Occurrence data on exotic ants derive from studies of three temperate regions. Our results suggest that the numbers of introduced or established ants may be much larger than the numbers so far documented. Ants introduced or established in new regions tend to arrive from the same or neighbouring realms, as would be expected if exotic species tend to match climates and if arrival/establishment is dependent upon higher trade rates from neighbouring countries. PMID- 25142203 TI - 3.88% efficient tin sulfide solar cells using congruent thermal evaporation. AB - Tin sulfide (SnS), as a promising absorber material in thin-film photovoltaic devices, is described. Here, it is confirmed that SnS evaporates congruently, which provides facile composition control akin to cadmium telluride. A SnS heterojunction solar cell is demons trated, which has a power conversion efficiency of 3.88% (certified), and an empirical loss analysis is presented to guide further performance improvements. PMID- 25142202 TI - Bone morphogenetic protein 4 inhibits liposaccharide-induced inflammation in the airway. AB - Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF-beta superfamily. The role of BMP4 in lung diseases is not fully understood. Here, we demonstrate that BMP4 was upregulated in lungs undergoing lipopolysaccharide (LPS)-induced inflammation, and in airway epithelial cells treated with LPS or TNF-alpha. BMP4 mutant (BMP4(+/-) ) mice presented with more severe lung inflammation in response to LPS or Pseudomonas aeruginosa, and lower bacterial load compared with that in BMP4(+/+) mice. Knockdown of BMP4 by siRNA increased LPS and TNF-alpha-induced IL-8 expression in 16HBE human airway epithelial cells and in primary human bronchial epithelial cells. Similarly, peritoneal macrophages from BMP4(+/-) mice produced greater levels of TNF-alpha and keratinocyte chemoattractant (KC) upon LPS treatment compared with cells from BMP4(+/+) mice. Administration of exogenous BMP4 attenuated the upregulation of TNF-alpha, IL-8, or KC induced by LPS and/or TNF alpha in airway epithelial cells, and peritoneal macrophages. Finally, partial deficiency of BMP4 in BMP4(+/-) mice protected the animals from restrictive lung function reduction upon chronic LPS exposure. These results indicate that BMP4 plays an important anti-inflammatory role, controlling the strength and facilitating the resolution of acute lung inflammation; yet, BMP4 also contributes to lung function impairment during chronic lung inflammation. PMID- 25142204 TI - Vestibular responses to direct stimulation of the human insular cortex. AB - OBJECTIVE: The present study provides a functional mapping of vestibular responses in the human insular cortex. METHODS: A total of 642 electrical stimulations of the insula were performed in 219 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory partial epilepsy. We retrospectively identified 41 contacts where stimulation elicited vestibular sensations (VSs) and analyzed their location with respect to (1) their stereotactic coordinates (for all contacts), (2) the anatomy of insula gyri (for 20 vestibular sites), and (3) the probabilistic cytoarchitectonic maps of the insula (for 9 vestibular sites). RESULTS: VSs occurred in 7.6% of the 541 evoked sensations after electrical stimulations of the insula. VSs were mostly obtained after stimulation of the posterior insula, that is, in the granular insular cortex and the postcentral insular gyrus. The data also suggest a spatial segregation of the responses in the insula, with the rotatory and translational VSs being evoked at more posterior stimulation sites than other less definable VSs. No left-right differences were observed. INTERPRETATION: These results demonstrate vestibular sensory processing in the insula that is centered on its posterior part. The present data add to the understanding of the multiple sensory functions of the insular cortex and of the cortical processing of vestibular signals. The data also indicate that lesion or dysfunction in the posterior insula should be considered during the evaluation of vestibular epileptic seizures. PMID- 25142205 TI - Assessment of high resolution melting analysis as a potential SNP genotyping technique in forensic casework. AB - High resolution melting (HRM) analysis is a simple, cost effective, closed tube SNP genotyping technique with high throughput potential. The effectiveness of HRM for forensic SNP genotyping was assessed with five commercially available HRM kits evaluated on the ViiATM 7 Real Time PCR instrument. Four kits performed satisfactorily against forensically relevant criteria. One was further assessed to determine the sensitivity, reproducibility, and accuracy of HRM SNP genotyping. The manufacturer's protocol using 0.5 ng input DNA and 45 PCR cycles produced accurate and reproducible results for 17 of the 19 SNPs examined. Problematic SNPs had GC rich flanking regions which introduced additional melting domains into the melting curve (rs1800407) or included homozygotes that were difficult to distinguish reliably (rs16891982; a G to C SNP). A proof of concept multiplexing experiment revealed that multiplexing a small number of SNPs may be possible after further investigation. HRM enables genotyping of a number of SNPs in a large number of samples without extensive optimization. However, it requires more genomic DNA as template in comparison to SNaPshot(r). Furthermore, suitably modifying pre-existing forensic intelligence SNP panels for HRM analysis may pose difficulties due to the properties of some SNPs. PMID- 25142206 TI - Editorial: the ten most highly cited articles. PMID- 25142208 TI - Benazepril affects integrin-linked kinase and smooth muscle alpha-actin expression in diabetic rat glomerulus and cultured mesangial cells. AB - BACKGROUND: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and is associated with excessive cardiovascular morbidity and mortality. The angiotensin converting enzyme inhibitor (ACEI) benazepril has been shown to slow the progression of chronic renal disease and have beneficial effects in patients with a combination of chronic renal disease and cardiovascular disease. Transforming growth factor-beta(1) (TGF-beta(1)) plays a central role in the pathogenesis and progression of DN. Integrin-linked kinase (ILK) can modulate TGF beta(1)-induced glomerular mesangial cell (GMC) injury, which is a prominent characteristic of renal pathology in kidney diseases. As an integrin cytoplasmic binding protein, ILK regulates fibronectin (FN) matrix deposition and the actin cytoskeleton. Smooth muscle alpha-actin (alpha-SMA) is involved in progressive renal dysfunction in both human and experimental renal disease. METHODS: To explore the mechanisms of benazepril's reno-protective effects, we examined the expression of TGF-beta(1), ILK, and alpha-SMA in GMC exposed to high glucose (HG) and in the kidneys of streptozotocin (STZ)-induced diabetic rats using real-time quantitative RT-PCR and western blot analysis. To elucidate the mechanism(s) of the effect of benazepril on GMC cellular processes, we assessed the effect of benazepril on Angiotensin II (Ang II) signalling pathways using western blot analysis. RESULTS: The expression of TGF-beta(1), ILK, and alpha-SMA increased significantly in the diabetic group compared with the control group. Benazepril treatment inhibited the expression of these genes in DN but failed to rescue the same levels in the control group. Similar results were found in GMC treated with HG or benazepril. Ang II increased ERK and Akt phosphorylation in the HG group, and benazepril could not completely block these responses, suggesting that other molecules might be involved in the progression of DN. Our findings suggest that benazepril decreases ILK and alpha-SMA expression, at least in part, by affecting the interactions between Ang II and TGF-beta(1). CONCLUSIONS: The findings described here support the hypothesis that the HG milieu of diabetes increases TGF-beta(1) secretion, which increases the synthesis of ILK and alpha-SMA that are involved in the progression of DN. This might be an important mechanism of the benazepril renal-protective function in the pathogenesis of DN. PMID- 25142210 TI - Aneurinibacillus soli sp. nov., isolated from mountain soil. AB - A novel bacterial strain designated CB4(T) was isolated from soil from the Hallasan, Jeju, Korea. Strain CB4(T) was found to be strictly aerobic, Gram-stain positive, rod-shaped, motile and formed creamy greyish colonies on nutrient agar. The major fatty acids were identified as iso-C(15:0) and iso-C(16:0), and the predominant isoprenoid quinone as MK-7. The cell-wall peptidoglycan contained glycine and alanine as the diagnostic amino acids and phosphatidyl-N methylethanolamine, phosphatidylethanolamine, diphosphatidylglycerol and an unidentified aminophospholipid as the polar lipids. The genomic DNA G+C content of strain CB4(T) was 46.5 mol%. Phylogenetic analysis, based on 16S rRNA gene sequence similarities, showed that strain CB4(T) forms a deep branch within the genus Aneurinibacillus, sharing the highest level of sequence homology with Aneurinibacillus aneurinilyticus DSM 5562(T) (96.5%). On the basis of the phenotypic, chemotaxonomic and phylogenetic characteristics, strain CB4(T) is considered to represent a novel species within the genus Aneurinibacillus, for which the name Aneurinibacillus soli sp. nov. is proposed. The type strain is CB4(T) ( =KCTC 33505(T) =CECT 8566(T)). An emended description of the genus Aneurinibacillus is also proposed. PMID- 25142207 TI - Overlapping patterns of brain activation to food and cocaine cues in cocaine abusers: association to striatal D2/D3 receptors. AB - Cocaine, through its activation of dopamine (DA) signaling, usurps pathways that process natural rewards. However, the extent to which there is overlap between the networks that process natural and drug rewards and whether DA signaling associated with cocaine abuse influences these networks have not been investigated in humans. We measured brain activation responses to food and cocaine cues with fMRI, and D2/D3 receptors in the striatum with [11C]raclopride and Positron emission tomography in 20 active cocaine abusers. Compared to neutral cues, food and cocaine cues increasingly engaged cerebellum, orbitofrontal, inferior frontal, and premotor cortices and insula and disengaged cuneus and default mode network (DMN). These fMRI signals were proportional to striatal D2/D3 receptors. Surprisingly cocaine and food cues also deactivated ventral striatum and hypothalamus. Compared to food cues, cocaine cues produced lower activation in insula and postcentral gyrus, and less deactivation in hypothalamus and DMN regions. Activation in cortical regions and cerebellum increased in proportion to the valence of the cues, and activation to food cues in somatosensory and orbitofrontal cortices also increased in proportion to body mass. Longer exposure to cocaine was associated with lower activation to both cues in occipital cortex and cerebellum, which could reflect the decreases in D2/D3 receptors associated with chronicity. These findings show that cocaine cues activate similar, though not identical, pathways to those activated by food cues and that striatal D2/D3 receptors modulate these responses, suggesting that chronic cocaine exposure might influence brain sensitivity not just to drugs but also to food cues. PMID- 25142211 TI - Genome-based reclassification of Bacillus cibi as a later heterotypic synonym of Bacillus indicus and emended description of Bacillus indicus. AB - While characterizing a related strain, it was noted that there was little difference between the 16S rRNA gene sequences of Bacillus indicus LMG 22858(T) and Bacillus cibi DSM 16189(T). Phenotypic characterization revealed differences only in the utilization of mannose and galactose and slight variation in pigmentation. Whole genome shotgun sequencing and comparative genomics were used to calculate established phylogenomic metrics and explain phenotypic differences. The full, genome-derived 16S rRNA gene sequences were 99.74% similar. The average nucleotide identity (ANI) of the two strains was 98.0%, the average amino acid identity (AAI) was 98.3%, and the estimated DNA-DNA hybridization determined by the genome-genome distance calculator was 80.3%. These values are higher than the species thresholds for these metrics, which are 95%, 95% and 70%, respectively, suggesting that these two strains should be classified as members of the same species. We propose reclassification of Bacillus cibi as a later heterotypic synonym of Bacillus indicus and an emended description of Bacillus indicus. PMID- 25142212 TI - Terrimonas arctica sp. nov., isolated from Arctic tundra soil. AB - A novel, Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, designated R9-86(T), was isolated from tundra soil collected near Ny-Alesund, Svalbard Archipelago, Norway (78 degrees N). Growth occurred at 4-28 degrees C (optimum, 22-25 degrees C) and at pH 6.0-9.0 (optimum, pH 7.0). Flexirubin-type pigments were absent. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain R9-86(T) belonged to the genus Terrimonas in the family Chitinophagaceae. 16S rRNA gene sequence similarities between strain R9-86(T) and the type strains of species of the genus Terrimonas with validly published names ranged from 93.7 to 95.0%. Strain R9-86(T) contained iso-C(15:1)-G (25.7%), iso C(15:0) (24.5%), iso-C(17:0)-3OH (18.3%) and summed feature 3 (C(16:1)omega7c and/or C(16:1)omega6c, 8.7%) as its major cellular fatty acids; phosphatidylethanolamine and an unknown polar lipid as its main polar lipids, and MK-7 as its predominant respiratory quinone. The DNA G+C content was 48.4 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain R9-86(T) is considered to represent a novel species of the genus Terrimonas, for which the name Terrimonas arctica sp. nov. is proposed. The type strain is R9-86(T) ( =CCTCC AB 2011004(T) =NRRL B-59114(T)). PMID- 25142213 TI - In-line microfluidic integration of photonic crystal fibres as a highly sensitive refractometer. AB - Photonic crystal fibres appear to be an ideal platform for the realisation of novel optofluidic devices and sensors due to their waveguide nature and microstructured architecture. In this paper, we present the fabrication and characterisation of an in-line photonic crystal fibre microfluidic refractometer enabled by a C-shaped fibre. The C-shaped fibre spliced in-between the photonic crystal fibre and the single-mode fibre allows simultaneous in-line optical signal delivery and analyte fluid feeding. Through an arc discharge pre-treatment technique, we successfully achieve selective exploitation of only the central two channels of the photonic crystal fibre for microfluidic sensing. After constructing a Sagnac interferometer, a highly sensitive refractometer with a sensitivity of 8699 nm per RIU was achieved experimentally; this agrees very well with the theoretical value of 8675 nm per RIU. As a demonstration for label-free optical sensing application, the refractometer was used to measure the concentration of NaCl solution with a sensitivity of 15.08 nm/(1 wt%) and a detection limit of 2.3 * 10(-3) wt% (23 ppm). PMID- 25142215 TI - Error-based training and emergent awareness in anosognosia for hemiplegia. AB - Residual forms of awareness have recently been demonstrated in subjects affected by anosognosia for hemiplegia, but their potential effects in recovery of awareness remain to date unexplored. Emergent awareness refers to a specific facet of motor unawareness in which anosognosic subjects recognise their motor deficits only when they have been requested to perform an action and they realise their errors. Four participants in the chronic phase after a stroke with anosognosia for hemiplegia were recruited. They took part in an "error-full" or "analysis of error-based" rehabilitative training programme. They were asked to attempt to execute specific actions, analyse their own strategies and errors and discuss the reasons for their failures. Pre- and post-training and follow-up assessments showed that motor unawareness improved in all four patients. These results indicate that unsuccessful action attempts with concomitant error analysis may facilitate the recovery of emergent awareness and, sometimes, of more general aspects of awareness. PMID- 25142214 TI - Chronic passive venous congestion drives hepatic fibrogenesis via sinusoidal thrombosis and mechanical forces. AB - Chronic passive hepatic congestion (congestive hepatopathy) leads to hepatic fibrosis; however, the mechanisms involved in this process are not well understood. We developed a murine experimental model of congestive hepatopathy through partial ligation of the inferior vena cava (pIVCL). C57BL/6 and transgenic mice overexpressing tissue factor pathway inhibitor (SM22alpha-TFPI) were subjected to pIVCL or sham. Liver and blood samples were collected and analyzed in immunohistochemical, morphometric, real-time polymerase chain reaction, and western blot assays. Hepatic fibrosis and portal pressure were significantly increased after pIVCL concurrent with hepatic stellate cell (HSC) activation. Liver stiffness, as assessed by magnetic resonance elastography, correlated with portal pressure and preceded fibrosis in our model. Hepatic sinusoidal thrombosis as evidenced by fibrin deposition was demonstrated both in mice after pIVCL as well as in humans with congestive hepatopathy. Warfarin treatment and TFPI overexpression both had a protective effect on fibrosis development and HSC activation after pIVCL. In vitro studies show that congestion stimulates HSC fibronectin (FN) fibril assembly through direct effects of thrombi as well as by virtue of mechanical strain. Pretreatment with either Mab13 or Cytochalasin-D, to inhibit beta-integrin or actin polymerization, respectively, significantly reduced fibrin and stretch-induced FN fibril assembly. CONCLUSION: Chronic hepatic congestion leads to sinusoidal thrombosis and strain, which in turn promote hepatic fibrosis. These studies mechanistically link congestive hepatopathy to hepatic fibrosis. PMID- 25142216 TI - Immunolocalization of scaffoldin, a trichohyalin-like protein, in the epidermis of the chicken embryo. AB - Recent comparative genomic studies have identified a chicken gene that codes for a trichohyalin-like protein rich in arginine and glutamic acid termed scaffoldin. Immunocytochemistry and immunoelectron microscopy show that this protein is predominantly localized in periderm granules, subcellular structures present in the periderm of the embryonic epidermis of chick scales, beak, claw, and in the sheath of developing and regenerating feathers. This suggests that scaffoldin contributes to the formation of periderm granules and to the soft cornification of the embryonic epidermis before the definitive epidermis is formed. Scaffoldin is absent from the definitive and adult epidermis generated underneath the periderm in scales and in inter-follicular regions. Scaffoldin mixes with corneous beta-proteins (beta-keratins) synthesized in keratinocytes of the transitional layers formed beneath the periderm in the subunguis of the developing claws. Immunoreactivity for scaffoldin is absent in keratinocytes that accumulate corneous beta-proteins such as those of scales, claws, and barbule barb cells of feathers. Corneous beta-proteins represent the prevalent type of proteins present in adult epidermis of claws, scales, and feathers. These observations indicate that scaffoldin is a protein of transitional epidermal cells of the avian integument and might represent an important component of periderm granules. PMID- 25142217 TI - A new chromone from Hymenocallis littoralis Salisb. (Amaryllidaceae). AB - A new chromone, 5,7-dihydroxy-6,8-dimethoxy-2-methyl-4H-chromen-4-one (1), together with seven known compounds, 5,7-dihydroxy-6-methoxy-2-methyl-4H-chromen 4-one (pisonin B) (2), 5,7-dihydroxy-2-methyl-4H-chromen-4-one (noreugenin) (3), 5-hydroxy-7-methoxy-2-methyl-4H-chromen-4-one (eugenin) (4), (2S)-7,4' dihydroxyflavan (5), 3',7-dihydroxy-4'-methoxy-8-methylflavan (6), 3',7-dihydroxy 4'-methoxyflavan (7) and 6,8-dimethyl-5,7,4'-trihydroxyflavanone (( - )-farrerol) (8), were isolated from Hymenocallis littoralis Salisb. (Amaryllidaceae) growing in Vietnam. Their structures were determined based on spectroscopic and physicochemical analyses. PMID- 25142218 TI - In vitro and in vivo metabolism of 14C-AZ11, a novel inhibitor of bacterial DNA gyrase/type II topoisomerase. AB - 1. (2R,4S,4aS)-11-Fluoro-2,4-dimethyl-8-((S)-4-methyl-2-oxooxazolidin-3-yl) 2,4,4a,6-tetrahydro-1H,1'H-spiro [isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline 5,5'-pyrimidine]-2',4',6'(3'H)-trione (AZ11) is a novel mode-of-inhibition bacterial topoisomerase inhibitor that entered preclinical development for the treatment of Gram-positive bacteria infection. 2. The in vitro biotransformation studies of AZ11 using mouse, rat, dog and human hepatocytes showed low-intrinsic clearance in all species attributed to microsomal metabolism. 3. After a single intravenous administration of [14C]AZ11 in bile duct cannulated rats, the mean percentage of dose recovered in rat urine, bile and feces was approximately 18, 36 and 42%, respectively. Unchanged AZ11 recovered in rat urine and bile was less than 9% of the dose, indicating that AZ11 underwent extensive metabolism in rats. 4. The most abundant in vivo metabolite detected in urine and bile was M1 formed via ring opening on the piperidine and morpholine rings accounting for 20% of the administered dose. The major fecal metabolite was M5, which accounted for approximately 32% of administered dose. M5 was not formed when AZ11 incubated with rat intestinal microsomes and cytosol but was formed when incubated with fresh rat feces, suggesting that unchanged AZ11 was directly excreted into gut lumen where M5 formed as an intestinal microflora-mediated product. This process could have significant impact on bioavailability or exposure of AZ11 in rat. PMID- 25142219 TI - Functional brush-decorated poly(globalide) films by ARGET-ATRP for bioconjugation. AB - Formation of hydroxyl functionalized poly(macrolactone) films was achieved by a combination of enzymatic ring opening polymerization of globalide and thiol-ene coupling reactions. Reaction with alpha-bromoisobutyryl bromide yielded ATRP initiator functional films. Efficient activator regeneration by electron transfer (ARGET) ATRP was employed for the polymerization of tert-butyl acrylate (tBA) and NIPAM from the initiator decorated surfaces. Deprotection of the tert-butyl ester decorated polymer films yielded carboxylic acid groups for convenient attachment of biomolecule. The successful conjugation of green fluorescent protein (eGFP) and active enzyme chitobiase (Chb) on densely poly(acrylic acid)-functionalized polyester films is demonstrated. PMID- 25142221 TI - The 2014 China meeting of the International Society for Vascular Surgery. AB - The 2014 meeting of the International Society for Vascular Surgery (ISVS) was held in Guangzhou, China, in conjunction with the fifth annual Wang Zhong-Gao's Vascular Forum, the eighth annual China Southern Endovascular Congress, and the third annual Straits Vascular Forum. Keynote addresses were given by Professors Christos Liapis, Wang Zhong-Gao, and Wang Shen-Ming. President Liapis presented the first ISVS Lifetime Achievement Award to Professor Wang Zhong-Gao for his multi-decade accomplishments establishing Vascular Surgery as a specialty in China. Faculty presentations were made in plenary sessions that focused on diseases relevant to the patterns of vascular disease prevalent in China. Thirty one abstracts were presented by vascular surgeons from around the globe, and the top 10 presentations were recognized. Thirteen countries were represented in the meeting. The 2014 ISVS meeting was a success. Partnership of this meeting with host Chinese Vascular Surgery societies was of mutual benefit, bringing vascular surgeons of international reputation to the local area for academic and intellectual exchange and formation of collaborations; integration of the meetings allows easier logistics to facilitate meeting organization and optimization of time for both faculty and attendees. This integrated model may serve as an optimal model for future meetings. PMID- 25142220 TI - Prevalence and determinants of Leishmania major infection in emerging and old foci in Tunisia. AB - BACKGROUND: Zoonotic Cutaneous Leishmaniasis (ZCL) due to Leishmania major (L. major) is still a serious public health problem in Tunisia. This study aimed to compare the prevalence and risk factors associated with L. major infection in old and new foci using leishmanin skin test (LST) in central Tunisia. METHODS: A cross sectional household survey was carried out between January and May 2009 on a sample of 2686 healthy individuals aged between 5 and 65 years. We determined the prevalence of L. major infection using the LST. Risk factors of LST positivity were assessed using a logistic regression model. RESULTS: The overall prevalence of LST positivity was 57% (95% CI: 53-59). The prevalence of L. major infection was significantly higher in the old focus (99%; 95% CI: 98-100) than in the emerging foci (43%; 95% CI: 39-46) (p = <0.001). Multivariate analysis of LST positivity risk factors showed that age, the nature of the foci (old/emerging), personal and family history of ZCL are determinants of positive LST results. CONCLUSION: The results updated the current epidemiologic profile of ZLC in central Tunisia. Past history of transmission in a population should be considered as a potential confounder in future clinical trials for drugs and vaccines against L. major cutaneous leishmaniasis. PMID- 25142222 TI - [Intensive care treatment before and after liver transplantation]. AB - BACKGROUND: Liver transplantation (LT) has become an established therapeutic option for patients with acute and chronic liver failure. Overall survival has dramatically increased over the last decades, mainly due to improved surgical techniques, the introduction of new immunosuppressive and anti-infective drugs but also due to continuous progress in the pre- and post-operative intensive care management of these patients. AIM: This article aims to give a short overview of the main aspects regarding pre- and post-LT critical care issues. RESULTS: Intensive care treatment plays a major role in the management of patients with acute and acute-on-chronic liver failure in order to enable a life-saving LT for these patients. Severe infections/sepsis mostly accompanied by multi-organ failure represent the major challenges for intensive care specialists. The immediate postoperative care takes place in the intensive care unit (ICU) in almost all patients. The expected ICU stay has been significantly shortened over the years to an average of about 1-2 days. Infections as well as acute kidney injury are the main complications in the first post-operative weeks being responsible for prolonged ICU stays. Immunologic and surgical complications are additional important issues in the post-LT intensive care setting. CONCLUSION: The intensive care management pre and post LT is an important, multidisciplinary challenge in the successful treatment of patients with acute and chronic liver failure. PMID- 25142223 TI - Wave reflections, arterial stiffness, heart rate variability and orthostatic hypotension. AB - Increased arterial stiffness and wave reflections are independently associated with orthostatic hypotension (OH). This study investigated whether heart rate variability (HRV) is also involved in the modulation of orthostatic blood pressure (BP) change. A total of 429 subjects (65.1 +/- 16.4 years, 77.4% men) were enrolled in this study. OH was defined as a ? 20 mm Hg decrease in brachial systolic blood pressure (SBP) or a ? 10 mm Hg diastolic blood pressure (DBP) decrease upon standing. Measurements of carotid-femoral pulse wave velocity (cf PWV) and the amplitude of the reflected pressure wave from a decomposed carotid pressure wave (Pb) were obtained by carotid tonometry in the supine position. The power spectrum from a 5-min recording of an electrocardiogram at rest was analyzed to provide components in the high frequency (HF) and low frequency (LF) ranges. Subjects with OH (n = 59, 13.8%) had significantly higher cf-PWV and Pb and significantly lower LogHF and LogLF than those without OH (n = 370). The cf PWV, Pb, LogHF and LogLF were significantly associated with postural SBP and DBP changes. Furthermore, cf-PWV but not Pb was significantly associated with LogHF and LogLF. Multivariate analysis showed that Pb (odds ratio (OR) per 1 s.d. 1.65, 95% confidence interval (CI) 1.282-2.137; P = 0.003) and LogHF (OR 0.628, 95% CI 0.459-0.860, P = 0.004), but not cf-PWV (OR 1.279, 95% CI 0.932-1.755, P = 0.128), were significant independent determinants of OH. Increased wave reflections may predispose OH independently of arterial stiffness and HRV. In contrast, increased arterial stiffness may cause OH through the modulation of HRV. PMID- 25142224 TI - Electrocardiographic changes in hypertensive disorders of pregnancy. PMID- 25142225 TI - Cardiac contractile function and mitochondrial respiration in diabetes-related mouse models. AB - BACKGROUND: Pathophysiological processes underlying diabetic-related cardiomyopathies are complex. Mitochondria dysfunction is often described as a cause of cardiac impairment but its extent may depend on the type of experimental diabetes. Here we proposed to compare drug- or diet-induced models of diabetes in terms of metabolic features, cardiac and mitochondrial functions. METHODS: Mice were fed with regular chow or fat-enriched diet. After three weeks, they received either citrate or streptozotocin injections for five consecutive days. Metabolic parameters, myocardial contractile function and mitochondrial respiration were measured after three more weeks. Fat mass volumes were assessed by magnetic resonance imaging. Oral glucose tolerance test, insulin tolerance test, triglyceride and adipocytokine quantification were evaluated to establish metabolic profiles. Cardiac function was assessed ex vivo onto a Langendorff column. Isolated cardiac mitochondria respiration was obtained using high resolution oxygraphy. RESULTS: Mice fed with the fat-enriched regimen presented abdominal obesity, increased blood glucose, elevated leptin level, glucose intolerance, and insulin resistance. Mice treated with streptozotocin, independently of the regimen, lost their capacity to release insulin in response to glucose ingestion. Mice fed with regular chow diet and injected with streptozotocin developed cardiac dysfunction without mitochondrial respiration defect. However, both groups of high-fat diet fed mice developed cardiac alterations associated with reduction in mitochondrial oxygen consumption, despite an increase in mitochondrial biogenesis signalling. CONCLUSIONS: We explored three animal models mimicking type 1 and 2 diabetes. While cardiac dysfunction was present in the three groups of mice, mitochondrial respiration impairment was only obvious in models reproducing features of type 2 diabetes. PMID- 25142227 TI - Modeling companion diagnostics in economic evaluations of targeted oncology therapies: systematic review and methodological checklist. AB - The successful use of a targeted therapy is intrinsically linked to the ability of a companion diagnostic to correctly identify patients most likely to benefit from treatment. The aim of this study was to review the characteristics of companion diagnostics that are of importance for inclusion in an economic evaluation. Approaches for including these characteristics in model-based economic evaluations are compared with the intent to describe best practice methods. Five databases and government agency websites were searched to identify model-based economic evaluations comparing a companion diagnostic and subsequent treatment strategy to another alternative treatment strategy with model parameters for the sensitivity and specificity of the companion diagnostic (primary synthesis). Economic evaluations that limited model parameters for the companion diagnostic to only its cost were also identified (secondary synthesis). Quality was assessed using the Quality of Health Economic Studies instrument. 30 studies were included in the review (primary synthesis n = 12; secondary synthesis n = 18). Incremental cost-effectiveness ratios may be lower when the only parameter for the companion diagnostic included in a model is the cost of testing. Incorporating the test's accuracy in addition to its cost may be a more appropriate methodological approach. Altering the prevalence of the genetic biomarker, specific population tested, type of test, test accuracy and timing/sequence of multiple tests can all impact overall model results. The impact of altering a test's threshold for positivity is unknown as it was not addressed in any of the included studies. Additional quality criteria as outlined in our methodological checklist should be considered due to the shortcomings of standard quality assessment tools in differentiating studies that incorporate important test-related characteristics and those that do not. There is a need to refine methods for incorporating the characteristics of companion diagnostics into model-based economic evaluations to ensure consistent and transparent reimbursement decisions are made. PMID- 25142226 TI - Notable epigenetic role of hyperhomocysteinemia in atherogenesis. AB - Atherosclerosis is associated with multiple genetic and modifiable risk factors. There is an increasing body of evidences to indicate that epigenetic mechanisms also play an essential role in atherogenesis by influencing gene expression. Homocysteine is a sulfur-containing amino acid formed during methionine metabolism. Elevated plasma level of homocysteine is generally termed as hyperhomocysteinemia. As a potential risk factor for cardiovascular diseases, hyperhomocysteinemia may initiate or motivate atherogenesis by modification of DNA methylation. The underlying epigenetic mechanism is still unclear with controversial findings. This review focuses on epigenetic involvement and mechanisms of hyperhomocysteinemia in atherogenesis. Considering the potential beneficial effects of anti-homocysteinemia treatments in preventing atherosclerosis, further studies on the role of hyperhomocysteinemia in atherogenesis are warranted. PMID- 25142228 TI - How might we increase physical activity through dog walking?: A comprehensive review of dog walking correlates. AB - BACKGROUND: Physical inactivity and sedentary behaviour are major threats to population health. A considerable proportion of people own dogs, and there is good evidence that dog ownership is associated with higher levels of physical activity. However not all owners walk their dogs regularly. This paper comprehensively reviews the evidence for correlates of dog walking so that effective interventions may be designed to increase the physical activity of dog owners. METHODS: Published findings from 1990-2012 in both the human and veterinary literature were collated and reviewed for evidence of factors associated with objective and self-reported measures of dog walking behaviour, or reported perceptions about dog walking. Study designs included cross-sectional observational, trials and qualitative interviews. RESULTS: There is good evidence that the strength of the dog-owner relationship, through a sense of obligation to walk the dog, and the perceived support and motivation a dog provides for walking, is strongly associated with increased walking. The perceived exercise requirements of the dog may also be a modifiable point for intervention. In addition, access to suitable walking areas with dog supportive features that fulfil dog needs such as off-leash exercise, and that also encourage human social interaction, may be incentivising. CONCLUSION: Current evidence suggests that dog walking may be most effectively encouraged through targeting the dog-owner relationship and by providing dog-supportive physical environments. More research is required to investigate the influence of individual owner and dog factors on 'intention' to walk the dog as well as the influence of human social interaction whilst walking a dog. The effects of policy and cultural practices relating to dog ownership and walking should also be investigated. Future studies must be of a higher quality methodological design, including accounting for the effects of confounding between variables, and longitudinal designs and testing of interventions in a controlled design in order to infer causality. PMID- 25142229 TI - Nucleotidyl transferase TUT1 inhibits lipogenesis in osteosarcoma cells through regulation of microRNA-24 and microRNA-29a. AB - Osteosarcoma is the most common type of bone cancer. In the present study, by way of PCR-based microarrays, we found that TUT1, a nucleotidyl transferase, was significantly downregulated in osteosarcoma, compared with adjacent normal tissues. In the current study, we performed PCR-based microarrays using the cDNA prepared from osteosarcoma and adjacent normal tissues. The enforced expression of TUT1 was able to inhibit cell proliferation in U2OS and MG63 cells, while its knockdown using small interfering RNA (siRNA) oligos promoted cell proliferation. At the molecular level, we found that TUT1 could inhibit the expression levels of PPARgamma and SREBP-1c, two key regulators in lipogenesis, through upregulation of microRNA-24 and microRNA-29a. Therefore, our results suggest that TUT1 may act as a tumor suppressor for osteosarcoma, which might provide a novel mechanism for the tumor development. PMID- 25142230 TI - Synuclein-gamma predicts poor clinical outcome in esophageal cancer patients. AB - The synuclein gamma (SNCG) protein, a member of neuronal protein family synuclein, has been considered as a promising potential biomarker as an indicator of cancer stage and survival in patients with cancer. The present study was conducted to evaluate the prognostic value of SNCG in patients with esophageal carcinoma (EC). SNCG levels were assessed immunohistochemically in cancer tissues from 73 EC patients. Median age was 57 (range, 29-78) years old. Forty-seven percent of the patients were male. Thirty-seven percent of the patients had upper or middle localized tumor whereas 59 % had epidermoid carcinoma. More than half of the patients (61 %) had undergone operation where 57 % received adjuvant treatment including chemotherapy or chemotherapy plus radiotherapy. Median overall survival was 11.3 +/- 1.8 months (95% confidence interval (CI): 7.7-14.9 months). SNCG positivity was significantly associated with the histological type of EC and inoperability (for SNCG positive vs. negative group; epidermoid 80 vs. 53 %; p = 0.05 and inoperable 59 vs.32 %; p = 0.04, respectively). Lymph node metastasis, inoperability and receiving no adjuvant treatment had significantly adverse effect on survival in the univariate analysis (p = 0.01, p < 0.001, and p = 0.001, respectively). SNCG positivity had significantly adverse effect on survival in both univariate and multivariate analysis (p = 0.02 and p = 0.01, respectively). Our results are the first to suggest that SNCG is a new independent predictor for poor prognosis in EC patients in the literature. PMID- 25142231 TI - Zoledronic acid induces apoptosis and autophagy in cervical cancer cells. AB - Cervical cancer is one of the most common gynecological cancers in association with high mortality and morbidity. The present study was aimed to investigate the in vitro effects of zoledronic acid (ZA) on viability and induction of apoptosis and autophagy as well as inflammatory effects in three human cervical cancer cell lines (HeLa, SiHa, and CaSki). Cell viability was measured by 3-(4,5 Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Induction of apoptosis was determined by quantitation of expression level of B cell lymphoma 2 (Bcl-2) and Bax messenger RNA (mRNA) and identification of the proteolytic cleavage of poly (ADP)-ribose polymerase (PARP) and caspase-3. Autophagic effects were examined by quantitation of mRNA expression of autophagy protein 5 (ATG5) and beclin1 and identifying accumulation of microtubule-associated protein 1 light chain 3 (LC3)-II. Inflammatory effect was determined by measuring expression and production of IL-6 and cyclooxygenase-2 (Cox-2). The results showed ZA significantly inhibited cell viability of cervical cancer cells. ZA induced cell death displayed features characteristic to both apoptosis and autophagy and was associated with different changes in the levels of Bcl-2 and Bax in the various cervical cancer lines. Expression of metastatic cytokines, IL 6 and Cox-2, was upregulated in the presence of ZA at low concentration. Our data revealed that ZA inhibits cervical cancer cells through the synergistic effect of apoptosis induction and autophagy activation. PMID- 25142232 TI - Overexpression of zinc finger E-box binding homeobox factor 1 promotes tumor invasiveness and confers unfavorable prognosis in esophageal squamous cell carcinoma. AB - Zinc finger E-box binding homeobox factor 1 (ZEB1), as a crucial mediator of "epithelial-mesenchymal transition," contributes to malignant progression of various epithelial tumors. However, its involvement in human esophageal squamous cell carcinoma (ESCC) remains unclear. In order to investigate the expression pattern of ZEB1 in ESCC tissues and evaluate its associations with tumor progression and patients' prognosis, 100 pairs of formalin-fixed and paraffin embedded cancerous and adjacent noncancerous tissues from patients with ESCC were used to detect the expression pattern of ZEB1 by immunohistochemistry. Then, the association between ZEB1 expression, clinicopathological parameters, and prognosis of ESCC was examined. We also performed migration and invasion assays of small interfering RNA (siRNA)-targeted ZEB1-transfected cells in vitro. As a result, expression level of ZEB1 was significantly higher in ESCC tissues compared to that in adjacent noncancerous tissues (P < 0.001). High expression of ZEB1 was observed in 55.00 % (55/100) of ESCCs. In addition, high ZEB1 expression was found to be closely correlated with advanced tumor stage (P = 0.001), positive lymph node metastasis (P = 0.001), great tumor depth (P = 0.03), and high histologic grade (P = 0.008). Moreover, multivariate analysis showed that the status of ZEB1 expression was an independent predictor for overall survival in ESCC. Furthermore, knockdown of ZEB1 by transfection of siRNA-ZEB1 abrogated the migration and invasion of ESCC cells in vitro. Taken together, our data offer the convincing evidence that ZEB1 may play a crucial role in promoting aggressive ESCC progression. ZEB1 may serve as an effective prognostic marker and a potential target for therapeutic intervention of ESCC. PMID- 25142233 TI - Immunization with a novel chimeric peptide representing B and T cell epitopes from HER2 extracellular domain (HER2 ECD) for breast cancer. AB - Because of direct stimulating immune system against disease, vaccination or active immunotherapy is preferable compared to passive immunotherapy. For this purpose, a newly designed chimeric peptide containing epitopes for both B and T cells from HER2 ECD subdomain III was proposed. To evaluate the effects of the active immunization, a discontinuous B cell epitope peptide was selected based on average antigenicity by bioinformatics analysis. The selected peptide was collinearly synthesized as a chimera with a T helper epitope from the protein sequence of measles virus fusion (208-302) using the GPSL linker. Three mice were immunized with the chimeric peptide. Reactive antibodies with HER2 protein in ELISA and immunofluorescence assays with no cross-reactivity were generated. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay indicated that the anti-peptide sera had inhibitory effects on proliferation of SK-BR-3 cells. Hence, the newly designed, discontinuous chimeric peptide representing B and T cell epitopes from subdomain III of HER2-ECD can form the basis for future vaccines design, where these data can be applied for monoclonal antibody production targeting the distinct epitope of HER2 receptor compared to the two broadly used anti-HER2 monoclonal antibodies, Herceptin and pertuzumab. PMID- 25142234 TI - miR-141 suppresses the growth and metastasis of HCC cells by targeting E2F3. AB - MicroRNAs (miRNAs) function as essential post-transcriptional modulators of gene expression involved in a wide range of physiologic and pathologic states, including cancer. Numerous miRNAs have been deregulated in hepatocellular carcinoma (HCC). Here, we investigated the role of miR-141 in HCC. Decreased expression of miR-141 was observed in both HCC tissues and cell lines. Ectopic overexpression of miR-141 reduced proliferation, migration, and invasion of HCC cells. E2F transcription factor 3 (E2F3) was confirmed to be a target of miR-141 in HCC cells. Moreover, restoration of E2F3 significantly reversed the tumor suppressive effects of miR-141. Our results suggest a critical role of miR-141 in suppressing metastasis of HCC cells by targeting E2F3. PMID- 25142235 TI - Improving the diagnosis, treatment, and biology patterns of feline mammary intraepithelial lesions: a potential model for human breast masses with evidence from epidemiologic and cytohistopathologic studies. AB - In this study, the frequency of different types of mammary masses and their relationship with cytohistopathologic changes was investigated and data on history, macroscopic description, clinical examination and treatment were collected. To determine the prevalence and types of cytohistopathologic changes, mammary glands from 12 female cats were evaluated. The mean age of cats at the time of diagnosis was 11.5 +/- 1.9 years (range 4-14 years), the mean gross size of the masses was 3.1 +/- 2.4 cm, 4/12 (33.3 %) masses were <=3.0 cm in diameter, and the maximum diameter of the largest mass had a median of 5 cm, with a range of diameter of 6 * 5 * 4 cm. Moreover, the preferential localization of mammary masses was the abdominal lobes (%50) and thoracic lobes (%33.3), and inguinal lobes (%16.7 of cases). Furthermore, two cases of the inguinal masses affected the caudo-inguinal lobe, six cases caudo-abdominal lobe, and thoracic masses were found in four cases. Eventually, six cases (%50) of masses were found in the right mammary lobes and six cases (%50) in the left mammary lobes. The majority of the masses revealed elastic (%50 of cases), hard (%25 of cases), or soft (%25 of cases) consistency. In the present study, according to the criteria of the veterinary and the medical WHO classification system, of the 12 cats with the cytohistopathological features of six (50 %) cases qualified abscess, 3 (25 %) cases as cystic hyperplasia and 3 (25 %) cases were called situ carcinoma. Whereas, all hyperplastic lesions (case nos. 7-9 and ranging in size from, 1 to >4 cm(3)) and carcinomas in situ lesions (case nos. 10-12 and ranging in size from, 1 to >3 cm(3)) were found incidentally upon routine cytohistology. Other lesions were observed grossly and removed either at surgery (case nos. 1-6). Finally, the cats were treated with unilateral lumpectomy (3 cases) and also, nine (75 %) cases had subsequent drainage, 3 (25 %) of which showed cystic hyperplasia and 6 (50 %) showed abscess on subsequent histopathological evaluation. Therefore, a correct diagnosis must be established quickly, and treatment must be instituted rapidly when alteration is noted in the mammary glands. PMID- 25142237 TI - Long-term intra-fractional motion of the prostate using hydrogel spacer during Cyberknife(r) treatment for prostate cancer--a case report. AB - BACKGROUND: There is a trend towards hypofractionated stereotactic radiotherapy (RT) in prostate cancer to apply high single doses in a few fractions. Using the Cyberknife(r) robotic system multiple non-coplanar fields are usually given with a treatment time of one hour or more. We planned to evaluate organ motion in this setting injecting a hydrogel spacer to protect the anterior rectal wall during treatment. METHODS: A 66 years old man with low risk prostate cancer was planned for robotic hypofractionated stereotactic RT. After implantation of fiducial markers and a hydrogel spacer a total dose of 36.25 Gy in 5 fractions was given to the planning target volume (clinical target volume + 3 mm). After each beam the corresponding data reporting on the intra-fractional movement were pre processed, the generated log-files extracted and the data analysed according to different directions: left -right (LR); anterior - posterior (AP); inferior superior (IS). Clinical assessments were prospectively done before RT start, one week after the end of treatment as well as 1, 6 and 12 months afterwards. Symptoms were documented using Common Toxicity and Adverse Events Criteria 4.0. RESULTS: Tolerability of marker and hydrogel implantation was excellent. A total of 284 non-coplanar fields were used per fraction. The total treatment time for all fields per fraction lasted more than 60 minutes. The detected and corrected movements over all 5 fractions were in a range of +/- 4 mm in all directions (LR: mean 0,238 - SD 0,798; AP: mean 0,450 - SD 1,690; and IS: mean 0,908 - SD 1,518). V36Gy for the rectum was 0.062 ccm. After RT, grade 1-2 intestinal toxicity and grade 1 genitourinarytoxicity occurred, but resolved completely after 10 days. On 1-, 6- and 12-months follow-up the patient was free of any symptoms with only slight decrease of erectile function (grade 1). There was a continuous PSA decline. CONCLUSIONS: Prostate movement was relatively low (+/- 4 mm) even during fraction times of more than 60 minutes. The hydrogel spacer might serve as a kind of stabilisator for the prostate, but this should be analysed in a larger cohort of patients. PMID- 25142236 TI - Increased expression of Chitinase 3-like 1 and microvessel density predicts metastasis and poor prognosis in clear cell renal cell carcinoma. AB - Increasing evidence demonstrated that Chitinase 3-like 1 (hereafter termed CHI3L1 or YKL-40) was highly expressed and tightly associated with human tumor development and progression. However, its precise role in clear cell renal cell carcinoma (hereafter termed RCC) remains to be delineated. In the present study, we investigated the relationship between CHI3L1 expression and microvessel density (MVD), a reflection of angiogenesis, with metastasis and prognosis in patients with clear cell renal cell carcinoma (RCC). Formalin-fixed, paraffin embedded tissue sections of clear cell RCC from 73 patients who had undergone radical nephrectomy were stained immunohistochemically with specific antibodies against CHI3L1 and CD34. CHI3L1 immunostaining was semi-quantitatively estimated based on the proportion (percentage of positive cells) and intensity. MVD was determined with CD34-stained slides. The expression pattern of CHI3L1 and MVD was compared with the clinicopathological variables. Twenty patients had either synchronous or metachronous metastases and 12 died during the follow-up. CHI3L1 intensity was significantly correlated with tumor size (P = 0.005), TNM stage (P = 0.027), M stage (P = 0.011), grade (P = 0.014), and metastasis (synchronous or metachronous; P < 0.001). The CHI3L1 proportion (P = 0.038) and MVD (P = 0.012) were significantly correlated with metastasis. MVD was correlated with CHI3L1 intensity (r = 0.376, P = 0.001) and CHI3L1 proportion (r = 0.364, P = 0.002). There was no difference in the expression of CHI3L1 and MVD between primary and metastatic sites. The survival of patients with higher CHI3L1 intensity was significantly worse than that of patients with lower CHI3L1 intensity. Multivariate analyses indicated that only M stage was an independent prognostic factor for cancer-specific survival and CHI3L1 expression was not an independent factor. Taken altogether, increased expression of CHI3L1 and MVD is associated with metastasis and a worse prognosis in clear cell RCC. CHI3L1 expression is correlated with MVD. The results suggest that CHI3L1 may be important in the progression and angiogenesis of clear cell RCC and CHI3L1 might be a novel strategy for therapy of the patients with RCC. PMID- 25142238 TI - Chloral hydrate in pediatric magnetic resonance imaging: evaluation of a 10-year sedation experience administered by radiologists. AB - BACKGROUND: Chloral hydrate is a sedative that has been used for magnetic resonance imaging (MRI). OBJECTIVE: To evaluate the use, effectiveness and safety of chloral hydrate administered by radiologists for the sedation of children who require MRI procedures. MATERIALS AND METHODS: We retrospectively reviewed the clinical charts for all patients ages 0 - 10 years old who underwent sedation with chloral hydrate for MRI from January 2000 to December 2010. Demographic factors, dose information, indication for MRI, therapeutic failures and adverse reactions to the drug were reviewed. RESULTS: One thousand, seven hundred and three children (946 males, 757 females) with a median age of 2.5 years (range: 4 days - 9.91 years) received chloral hydrate. Moderate to deep sedation was achieved in 1,618/1,703 (95%) of the patients, 35/1,703 (2.1%) of the patients failed to achieve moderate to deep sedation, and 47/1,703 (2.8%) of the patients woke up during MRI examination. Adverse reactions were present in 31/1,703 (1.8%) of the patients. Three severe adverse reactions occurred (0.18%). A single dose of chloral hydrate (40-60 mg/kg) was administered to 1,477/1,703 patients (86.7%). An additional dose of chloral hydrate (10-20 mg/kg), given 15 min after the first dose or when the patient woke up during the MRI examination, was required in 226/1,703 patients (13.3%). The likelihood of requiring an additional dose in children older than 2 years was 2.2 times the likelihood compared to children younger than 2 years (OR = 2.2 [95%CI: 1.6-3.0]). The use of a reduced dose (<50 mg/kg) was not associated with a higher therapeutic failure rate (OR = 1.04 [95%CI 0.57-1.89]). CONCLUSION: Chloral hydrate is an appropriate sedation option for pediatric patients in MRI services when strict patient selection criteria are met. The use of a reduced dose does not affect the effectiveness of sedation. The lack of data regarding the presence of transient oxygen desaturation, the time to induce sedation and the exact duration of sedation are limitations of this study. PMID- 25142239 TI - Diffuse intrinsic pontine glioma: is MRI surveillance improved by region of interest volumetry? AB - BACKGROUND: Paediatric diffuse intrinsic pontine glioma (DIPG) is noteworthy for its fibrillary infiltration through neuroparenchyma and its resultant irregular shape. Conventional volumetry methods aim to approximate such irregular tumours to a regular ellipse, which could be less accurate when assessing treatment response on surveillance MRI. Region-of-interest (ROI) volumetry methods, using manually traced tumour profiles on contiguous imaging slices and subsequent computer-aided calculations, may prove more reliable. OBJECTIVE: To evaluate whether the reliability of MRI surveillance of DIPGs can be improved by the use of ROI-based volumetry. MATERIALS AND METHODS: We investigated the use of ROI- and ellipsoid-based methods of volumetry for paediatric DIPGs in a retrospective review of 22 MRI examinations. We assessed the inter- and intraobserver variability of the two methods when performed by four observers. RESULTS: ROI- and ellipsoid-based methods strongly correlated for all four observers. The ROI based volumes showed slightly better agreement both between and within observers than the ellipsoid-based volumes (inter-[intra-]observer agreement 89.8% [92.3%] and 83.1% [88.2%], respectively). Bland-Altman plots show tighter limits of agreement for the ROI-based method. CONCLUSION: Both methods are reproducible and transferrable among observers. ROI-based volumetry appears to perform better with greater intra- and interobserver agreement for complex-shaped DIPG. PMID- 25142240 TI - Earliest videofluoromanometric pharyngeal signs of dysphagia in ALS patients. AB - The aim of this study was to find whether there are manometric pharyngeal changes that may have diagnostic and prognostic relevance in the amyotrophic lateral sclerosis (ALS) patient who does not show changes in contrast-medium oropharyngeal transit in a videofluoroscopic swallowing study. Ten ALS patients, with an ALS Severity Scale Score of at least 7, no need to change dietary habit, no aspiration and/or penetration, and no other changes in contrast-medium oropharyngeal transit, were collected from our institution's database of videofluoromanometric swallowing studies. They were included in the study together with a group of 11 healthy volunteers. For each subject, 12 manometric items-7 for the pharyngeal phase and 5 for UES functionality-were evaluated. Statistically significant differences between the ALS patients and the healthy volunteers were found for pharyngeal contraction time of the upper region (median = 1,120, range = 880-1,420 vs. median = 970, range = 800-1,140), pharyngeal contraction time of the intermediate region (median = 1140, range = 960-1,360 vs. median = 770, range = 280-1,180), pharyngeal contraction time of the lower region (median = 1,320, range = 920-1,760 vs. median = 800, range = 620-1,780), and residual pressure after the relaxation of the UES (median = 2.2, range = -20.2 to 27.8 vs. median = -5.7, range = -2.9 to 8.4). A videofluoromanometric swallowing study may show an increase in the pharyngeal contraction time and in residual pressure after relaxation of the UES in ALS patients without videofluoroscopic changes in contrast-medium oropharyngeal transit. PMID- 25142241 TI - Frequency of stage II oral transport cycles in healthy human. AB - Stage II transport (St2Tr) is propulsion of triturated food into the pharynx for storage before swallowing via tongue squeeze-back against the palate. To clarify the phenomenology of St2Tr, we examined the effects of food consistency and the number of chewing cycles on the number of St2Tr cycles in a chew-swallow sequence. We recorded chew-swallow sequences in lateral projection with videofluoroscopy of 13 healthy volunteers eating 6 g of hard (shortbread cookie), and soft foods (ripe banana and tofu) with barium. We counted the number of chewing and St2Tr cycles from food intake to terminal swallow. We used the Friedman test for bivariate analyses and negative binomial regression for multivariable analyses. On bivariate analysis, food consistency had a positive association with the number of chewing cycles (P = 0.013), but not with the number of St2Tr cycles (P = 0.27). Multivariable analysis, however, revealed a greater number of St2Tr cycles with hard than soft food (P <= 0.01) and a trend toward negative correlation between the numbers of St2Tr and chewing cycles (P = 0.083). The number of chewing cycles needed to clear the mouth differs among food consistencies as demonstrated previously. Greater numbers of both St2Tr and chewing cycles were elicited with the hard than with the soft foods. Given the trend toward negative correlation, the association between the number of St2Tr cycles and that of chewing cycles deserves further study. PMID- 25142242 TI - Electromyography of swallowing with fine wire intramuscular electrodes in healthy human: activation sequence of selected hyoid muscles. AB - Few studies have reported the activation sequence of the swallowing muscles in healthy human participants. We examined temporal characteristics of selected hyoid muscles using fine wire intramuscular electromyography (EMG). Thirteen healthy adults were studied using EMG of the anterior belly of digastric (ABD), geniohyoid (GH), sternohyoid (SH), and masseter (MA, with surface electrodes) while ingesting thin liquid, banana, tofu, and cookie (3 trials each). Onset timing was measured from rectified and integrated EMG. Data were analyzed using repeated-measures ANOVA with Bonferroni correction. When drinking thin liquid, MA, GH, and ABD were activated almost simultaneously, but SH was activated later (using GH onset as 0 s, MA -0.07 (-0.20 to 0.17) second [median (interquartile range)]; ABD 0.00 (-0.10 to 0.07) second; SH 0.17 (0.02 to 0.37) second; P < 0.01). With solid foods, MA contraction preceded GH and ABD; SH was last and delayed relative to liquid swallows (GH 0 s; MA -0.17 (-0.27 to 0.07) second; ABD 0.00 (-0.03 to 0.03) second; SH 0.37 (0.23 to 0.50) second; P < 0.01). The role of the MA differs between solids and liquids so the variation in its timing is expected. The synchronous contraction of GH and ABD was consistent with their role in hyolaryngeal elevation. The SH contracted later with solids, perhaps because if the longer duration of the swallow. The consistent pattern among foods supports the concept of a central pattern generator for pharyngeal swallowing. PMID- 25142243 TI - Anatomical considerations of the longitudinal pharyngeal muscles in relation to their function on the internal surface of pharynx. AB - The aim of this study was to clarify the topography of the longitudinal pharyngeal muscles and to relate the findings to pharyngeal muscular function. Forty-four specimens (22 right and 22 left sides) from embalmed Korean adult cadavers (13 males, 9 females; age range, 46-89 years; mean age, 69.2 years) were used in this study. The palatopharyngeus muscle originated from the palatine aponeurosis and the median part of the soft palate on oral aspect; it ran downward and lateralward, respectively. The palatopharyngeus muscle, which held the levator veli palatini, was divided into two bundles, medial and lateral, according to the positional relationship with the levator veli palatini. The lateral bundle of the palatopharyngeus muscle was divided into two parts: longitudinal and transverse. The pharyngeal longitudinal muscles were classified into the following four types (I-IV) depending on the area of insertion: they were inserted into the palatine tonsil, epiglottis, arytenoid cartilage, piriform recess, thyroid cartilage, and pharyngeal wall. The transverse part of the palatopharyngeus muscle plays a role as a sphincter. Palatopharyngeus and levator veli palatini muscles help each other to function effectively in the soft palate. The present findings suggest that the pharyngeal muscles are involved not only in swallowing but also in respiration and phonation via their attachment to the laryngeal cartilage. PMID- 25142244 TI - Unfreezing the Flexnerian Model: introducing longitudinal integrated clerkships in rural communities. AB - INTRODUCTION: Physician shortages in rural areas remain severe but may be ameliorated by recent expansions in medical school class sizes. Expanding student exposure to rural medicine by increasing the amount of prolonged clinical experiences in rural areas may increase the likelihood of students pursuing a career in rural medicine. This research sought to investigate the perspective of rural physicians on the introduction of a rurally based nine-month Longitudinal Integrated Clerkship (LIC). METHODS: In this mixed-methods study, nine physician leaders were interviewed from five Maine, USA, rural hospitals participating in an LIC. Semi-structured interviews were audiotaped and transcribed. Qualitative analysis techniques were used to code the transcripts and develop themes. Forty seven participating rural LIC preceptors were also surveyed through an online survey. RESULTS: Four major themes related to implementing the LIC model emerged: (1) melting old ways, (2) overcoming fears, (3) synergy of energy, and (4) benefits all-around. The faculty were very positive about the LIC, with increased job satisfaction, practice morale, and ongoing learning, but concerned about the financial impact on productivity. CONCLUSIONS: The importance of these themes and perceptions are discussed within the three-stage model of change by Lewin. These results describe how the innovative LIC model can conceptually unfreeze the traditional Flexnerian construct for rural physicians. Highlighting the many stakeholder benefits and addressing the anxieties and fears of rural faculty may facilitate the implementation of a rural LIC. Given the net favorable perception of rural faculty of the LIC, this educational model has the potential to play a major role in increasing the rural workforce. PMID- 25142245 TI - Molecular characterization of circulating tumor cells: Holy Grail for personalized cancer treatment? PMID- 25142246 TI - Tacrolimus pharmacodynamics and pharmacogenetics along the calcineurin pathway in human lymphocytes. AB - BACKGROUND: Although therapeutic drug monitoring has improved the clinical use of immunosuppressive drugs, there is still interpatient variability in efficacy and toxicity that pharmacodynamic monitoring may help to reduce. To select the best biomarkers of tacrolimus pharmacodynamics, we explored the strength and variability of signal transduction and the influence of polymorphisms along the calcineurin pathway. METHODS: Peripheral blood mononuclear cells from 35 healthy volunteers were incubated with tacrolimus (0.1-50 ng/mL) and stimulated ex vivo. Inhibition of NFAT1 (nuclear factor of activated T cells 1) translocation to the nucleus and intracellular expression of interleukin-2 in CD4(+) and CD8(+) T cells and the surface activation marker CD25 in CD3(+) cells were measured by flow cytometry. We sequenced the promoter regions of immunophilins and calcineurin subunits and characterized selected single nucleotide polymorphisms in the genes of the calcineurin pathway with allelic discrimination assays. RESULTS: All responses closely fitted an I/Imax sigmoid model. Large interindividual variability (n = 30) in I0 and IC50 was found for all biomarkers. Moreover, strong and statistically significant associations were found between tacrolimus pharmacodynamic parameters and polymorphisms in the genes coding cyclophilin A, the calcineurin catalytic subunit alpha isoenzyme, and CD25. CONCLUSIONS: This study demonstrates the consistency and large interindividual variability of signal transduction along the calcineurin pathway, as well as the strong influence of pharmacogenetic polymorphisms in the calcineurin cascade on both the physiological activity of this route and tacrolimus pharmacodynamics. PMID- 25142247 TI - A review of multidisciplinary clinical practice guidelines in suicide prevention: toward an emerging standard in suicide risk assessment and management, training and practice. AB - OBJECTIVE: The current paper aims to: (1) examine clinical practice guidelines in suicide prevention across fields, organizations, and clinical specialties and (2) inform emerging standards in clinical practice, research, and training. METHODS: The authors conducted a systematic literature review to identify clinical practice guidelines and resource documents in suicide prevention and risk management. The authors used PubMed, Google Scholar, and Google Search, and keywords included: clinical practice guideline, practice guideline, practice parameters, suicide, suicidality, suicidal behaviors, assessment, and management. To assess for commonalities, the authors reviewed guidelines and resource documents across 13 key content categories and assessed whether each document suggested validated assessment measures. RESULTS: The search generated 101 source documents, which included N = 10 clinical practice guidelines and N = 12 additional resource documents (e.g., non-formalized guidelines, tool-kits). All guidelines (100 %) provided detailed recommendations for the use of evidence based risk factors and protective factors, 80 % provided brief (but not detailed) recommendations for the assessment of suicidal intent, and 70 % recommended risk management strategies. By comparison, only 30 % discussed standardization of risk level categorizations and other content areas considered central to best practices in suicide prevention (e.g., restricting access to means, ethical considerations, confidentiality/legal issues, training, and postvention practices). Resource documents were largely consistent with these findings. CONCLUSIONS: Current guidelines address similar aspects of suicide risk assessment and management, but significant discrepancies exist. A lack of consensus was evident in recommendations across core competencies, which may be improved by increased standardization in practice and training. Additional resources appear useful for supplemental use. PMID- 25142249 TI - Experiences of Using Prezi in Psychiatry Teaching. AB - OBJECTIVE: Prezi is a presentation software allowing lecturers to develop ideas and produce mind maps as they might do on an old-style blackboard. This study examines students' experience of lectures presented using Prezi to identify the strengths and weaknesses of this new teaching medium. METHODS: Prezi was used to present mental health lectures to final-year medical and physiotherapy students. These lectures were also available online. This cross-sectional study used a questionnaire to assess students' experience of the software. RESULTS: Of students approached, 75.5 % (74/98) took part in the study. A majority, 98.6 % (73/74), found Prezi to be a more engaging experience than other styles of lecture delivery. The overview or "mind map" provided by Prezi was found to be helpful by 89.2 % (66/74). Problems arose when students used Prezi in their personal study, with 31.1 % (23/74) reporting some difficulties, mostly of a technical nature. CONCLUSION: This study highlights the potential of Prezi for providing students with an engaging and stimulating educational experience. For Prezi to be effective, however, the lecturer has to understand and be familiar with the software and its appropriate use. PMID- 25142251 TI - Quantifying publication scholarly activity of psychiatry residency training directors. AB - OBJECTIVE: The authors quantify the number of PubMed-indexed publications by psychiatry program directors during a 5-year observation period. METHODS: The authors obtained the names of general adult, child and adolescent, and geriatric psychiatry program directors from the ACGME website and entered them into a PubMed.gov database search. Then, they counted the number of indexed publications from July 2008 to June 2013 and categorized them by academic year. RESULTS: The median number of publications was one for adult psychiatry program directors (n=184), one for child and adolescent directors (n=121), and three for geriatric psychiatry directors (n=58). CONCLUSIONS: The number of PubMed-indexed publications for program directors of general adult, child and adolescent, and geriatric psychiatry residencies is relatively low. Further research is needed to identify and examine the challenges facing program directors that may limit their ability to participate in this form of scholarly activity. PMID- 25142252 TI - The importance of code status discussions in the psychiatric hospital: results of a single site survey of psychiatrists. AB - OBJECTIVES: Documentation of code status is a requirement with hospital admission, yet this discussion may present unique challenges with psychiatric inpatients. Currently, no standards exist on conducting these discussions with psychiatric inpatients. The authors surveyed psychiatry trainees and faculty regarding their perceptions and practice to gain further insight into the types of approaches used. METHODS: The authors conducted an IRB-approved, Web-based survey of psychiatry faculty and trainees using a 25-item questionnaire of demographics and opinions about code status among psychiatric inpatients. RESULTS: The response rate was 36.1 % (n = 30; 15 faculty and 15 trainees). Respondents felt that it was important to discuss code status with each admission. Faculty placed a higher emphasis on assessing patients with a recent suicide attempt (p = 0.024). CONCLUSION: Psychiatric faculty and trainees endorsed the importance of assessing code status with each admission. The authors suggest that educational programs are needed on strategies to conduct code status discussions properly and effectively in psychiatric populations. PMID- 25142250 TI - College Students: Mental Health Problems and Treatment Considerations. AB - Attending college can be a stressful time for many students. In addition to coping with academic pressure, some students have to deal with the stressful tasks of separation and individuation from their family of origin while some may have to attend to numerous work and family responsibilities. In this context, many college students experience the first onset of mental health and substance use problems or an exacerbation of their symptoms. Given the uniqueness of college students, there is a need to outline critical issues to consider when working with this population. In this commentary, first, the prevalence of psychiatric and substance use problems in college students and the significance of assessing age of onset of current psychopathology are described. Then, the concerning persistent nature of mental health problems among college students and its implications are summarized. Finally, important aspects of treatment to consider when treating college students with mental health problems are outlined, such as the importance of including parents in the treatment, communicating with other providers, and employing of technology to increase adherence. It is concluded that, by becoming familiar with the unique problems characteristic of the developmental stage and environment college students are in, practitioners will be able to better serve them. PMID- 25142254 TI - Pathways of cylindrical orientations in PS-b-P4VP diblock copolymer thin films upon solvent vapor annealing. AB - The orientation changes of perpendicular cylindrical microdomains in polystyrene block-poly(4-vinylpyridine) (PS-b-P4VP) thin films upon annealing in different solvent vapors were investigated by in situ grazing incidence small-angle X-ray scattering (GISAXS) and ex situ scanning force microscopy (SFM). The swelling of P4VP perpendicular cylinders (C?) in chloroform, a non-selective solvent vapor, leads to the reorientation to in-plane cylinders through a disordered state in a particular kinetic pathway in the phase diagram upon drying. On the other hand, the swelling of the P4VP perpendicular cylinders in a selective solvent vapor (i.e., 1,4-dioxane) induces a morphological transition from cylindrical to ellipsoidal as a transient structure to spherical microdomains; subsequent solvent evaporation resulted in shrinkage of the matrix in the vertical direction, merging the ellipsoidal domains into the perpendicularly aligned cylinders. In this paper, we have discussed the mechanism based on the selectivity of the solvent to the constituting blocks that is mainly responsible for the orientation changes. PMID- 25142253 TI - Genome-wide comparison of microRNAs and their targeted transcripts among leaf, flower and fruit of sweet orange. AB - BACKGROUND: In plants, microRNAs (miRNAs) regulate gene expression mainly at the post-transcriptional level. Previous studies have demonstrated that miRNA mediated gene silencing pathways play vital roles in plant development. Here, we used a high-throughput sequencing approach to characterize the miRNAs and their targeted transcripts in the leaf, flower and fruit of sweet orange. RESULTS: A total of 183 known miRNAs and 38 novel miRNAs were identified. An in-house script was used to identify all potential secondary siRNAs derived from miRNA-targeted transcripts using sRNA and degradome sequencing data. Genome mapping revealed that these miRNAs were evenly distributed across the genome with several small clusters, and 69 pre-miRNAs were co-localized with simple sequence repeats (SSRs). Noticeably, the loop size of pre-miR396c was influenced by the repeat number of CUU unit. The expression pattern of miRNAs among different tissues and developmental stages were further investigated by both qRT-PCR and RNA gel blotting. Interestingly, Csi-miR164 was highly expressed in fruit ripening stage, and was validated to target a NAC transcription factor. This study depicts a global picture of miRNAs and their target genes in the genome of sweet orange, and focused on the comparison among leaf, flower and fruit tissues. CONCLUSIONS: This study provides a global view of miRNAs and their target genes in different tissue of sweet orange, and focused on the identification of miRNA involved in the regulation of fruit ripening. The results of this study lay a foundation for unraveling key regulators of orange fruit development and ripening on post transcriptional level. PMID- 25142255 TI - Calcitonin gene-related peptide inhibits human immunodeficiency type 1 transmission by Langerhans cells via an autocrine/paracrine feedback mechanism. AB - AIM: Peripheral neurones innervating mucosal epithelia are in direct contact with resident immune cells, including Langerhans cells (LCs). Such neurones secrete the neuropeptide calcitonin gene-related peptide (CGRP) that modulates LCs function. We recently found that CGRP strongly inhibits human immunodeficiency virus type 1 (HIV-1) transmission, by interfering with multiple steps of mucosal LC-mediated HIV-1 transfer, including increased expression of the LC-specific lectin langerin. Herein, we investigated the anti-HIV-1 mechanism of CGRP. METHODS: In the presence of CGRP, HIV-1 transfer from LCs to CD4+ T cells was tested with viral clones using either the HIV-1 co-receptor CCR5 (R5) or CXCR4 (X4). Surface expression of CCR5, CXCR4 and langerin was evaluated by flow cytometry. CGRP secretion by LCs was measured with an enzyme immunoassay. Expression of the multimeric CGRP receptor was examined by quantitative real-time RT-PCR and immuno-fluorescent microscopy. RESULTS: Calcitonin gene-related peptide decreased transfer of HIV-1 R5, but increased that of X4. These opposing effects correlated with decreased CCR5 vs. increased CXCR4 surface expression in LCs. Inhibition of HIV-1 R5 transfer by CGRP involved signal transducer and activator of transcription 4 (STAT4) activation. Both alphaCGRP and betaCGRP were similarly efficient in decreasing HIV-1 R5 transfer and increasing langerin expression. LCs secreted low basal levels of endogenous CGRP, which increased markedly following CGRP treatment. CGRP also increased expression of its cognate receptor in LCs. CONCLUSION: CGRP engages a positive feedback mechanism that would further enhance its anti-HIV-1 activity. This information might be relevant for the therapeutic use of CGRP as a prophylactic agent against HIV-1. PMID- 25142256 TI - Analyzing Test-Taking Behavior: Decision Theory Meets Psychometric Theory. AB - We investigate the implications of penalizing incorrect answers to multiple choice tests, from the perspective of both test-takers and test-makers. To do so, we use a model that combines a well-known item response theory model with prospect theory (Kahneman and Tversky, Prospect theory: An analysis of decision under risk, Econometrica 47:263-91, 1979). Our results reveal that when test takers are fully informed of the scoring rule, the use of any penalty has detrimental effects for both test-takers (they are always penalized in excess, particularly those who are risk averse and loss averse) and test-makers (the bias of the estimated scores, as well as the variance and skewness of their distribution, increase as a function of the severity of the penalty). PMID- 25142257 TI - Conversion from calcineurin inhibitor-based immunosuppression to mammalian target of rapamycin inhibitors or belatacept in renal transplant recipients. AB - The calcineurin inhibitors (CNIs) remain the standard of care for maintenance immunosuppression following renal transplantation. CNIs have demonstrated their effectiveness in reducing acute cellular rejection; however, some evidence suggests that these compounds negatively affect native renal function and are associated with allograft injury in renal transplant recipients. CNIs have also been linked with hypertension, new-onset diabetes after transplantation, tremor, and thrombotic microangiopathy, which have significant consequences for long-term allograft function and patient health overall. Thus, converting patients to a non CNI-based regimen may improve renal function and also provide extrarenal benefits. A number of studies have been conducted that explore CNI conversion strategies in renal transplant recipients in an effort to improve long-term allograft function and survival. These include converting to alternative, non nephrotoxic, maintenance immunosuppressants, such as the mammalian target of rapamycin inhibitors (sirolimus and everolimus) and the costimulation blocker belatacept. In this review of literature, evidence for the potential renal and extrarenal benefits of conversion to these non-CNI-based regimens is evaluated. Clinical challenges, including the adverse event profiles of non-CNI-based regimens and the selection of candidates for conversion, are also examined. PMID- 25142260 TI - Photoperiod constraints on tree phenology, performance and migration in a warming world. AB - Increasing temperatures should facilitate the poleward movement of species distributions through a variety of processes, including increasing the growing season length. However, in temperate and boreal latitudes, temperature is not the only cue used by trees to determine seasonality, as changes in photoperiod provide a more consistent, reliable annual signal of seasonality than temperature. Here, we discuss how day length may limit the ability of tree species to respond to climate warming in situ, focusing on the implications of photoperiodic sensing for extending the growing season and affecting plant phenology and growth, as well as the potential role of photoperiod in controlling carbon uptake and water fluxes in forests. We also review whether there are patterns across plant functional types (based on successional strategy, xylem anatomy and leaf morphology) in their sensitivity to photoperiod that we can use to predict which species or groups might be more successful in migrating as the climate warms, or may be more successfully used for forestry and agriculture through assisted migration schemes. PMID- 25142259 TI - Non-surgical periodontal therapy with systemic antibiotics in patients with untreated chronic periodontitis: a systematic review and meta-analysis. AB - OBJECTIVE: The purpose of this meta-analysis is to evaluate the effectiveness of different systemic antibiotics in combination with scaling and root planing (SRP) when compared to SRP alone in patients with untreated chronic periodontitis. BACKGROUND: Although chronic periodontitis is mostly treated without adjunctive systemic antibiotics, some recent meta-analyses have shown clinical benefit for some systemic antibiotics when used as an adjunct to SRP. However, there is a wide variety of systemic antibiotic regimens used today. It remains unclear if the selected type of systemic antibiotic influences the magnitude of clinical benefit. MATERIAL AND METHODS: The MEDLINE-PubMed database was searched from their earliest records through May 16, 2013. Several journals were hand searched and some authors were contacted for additional information. Outcome measures analysed were mean bleeding on probing change, mean clinical attachment level gain and mean probing pocket depth reduction. Extracted data were pooled using a random effect model. Weighted mean differences were calculated and heterogeneity was assessed. RESULTS: The search yielded 281 abstracts. Ultimately, 95 studies were selected, describing 43 studies meeting the eligibility criteria. Systemic antibiotics showed a significant (p < 0.05) additional pocket depth reduction for moderate (at 3 mo 0.27 mm +/- 0.09, at 6 mo 0.23 mm +/- 0.10 and at 12 mo 0.25 mm +/- 0.27) and deep pockets (at 3 mo 0.62 mm +/- 0.17, at 6 mo 0.58 mm +/- 0.16 and at 12 mo 0.74 mm +/- 0.30). Statistically, no specific type of antibiotic was superior over another. However, when analysing the clinical data for initially moderate pockets or deep pockets, some trends became apparent. CONCLUSION: Systemic antibiotics combined with SRP offer additional clinical improvements compared to SRP alone. Although there were no statistically significant differences, there was a trend that for initially moderate and deep pockets, metronidazole or metronidazole combined with amoxicillin, resulted in clinical improvements that were more pronounced over doxycycline or azithromycin. Additionally, there was a trend that the magnitude of the clinical benefit became smaller over time (1 year). PMID- 25142258 TI - Phase I dose-escalation study of SGN-75 in patients with CD70-positive relapsed/refractory non-Hodgkin lymphoma or metastatic renal cell carcinoma. AB - PURPOSE: This first-in-human study evaluated the CD70-targeted antibody-drug conjugate SGN-75 in patients with relapsed or refractory CD70-positive non Hodgkin lymphoma (NHL) or metastatic renal cell carcinoma (RCC). Methods SGN-75 was administered intravenously to 58 patients (39 RCC, 19 NHL) every 3 weeks (Q3Wk; doses escalated from 0.3 to 4.5 mg/kg) or on Days 1, 8, and 15 of 28-day cycles (weekly; doses of 0.3 or 0.6 mg/kg). Dose-limiting toxicities were evaluated during Cycle 1; treatment response was monitored every 2 cycles. RESULTS: The maximum tolerated dose of SGN-75 in RCC patients was 3 mg/kg Q3Wk. Due to toxicity concerns (idiopathic thrombocytopenic purpura in 2 NHL patients treated weekly), dose escalation in the weekly schedule was terminated; no regimen was recommended for NHL patients. The most common adverse events reported in patients treated Q3Wk (N = 47) were fatigue (40%), dry eye (32%), nausea (30%), and thrombocytopenia (26%). The nadir for thrombocytopenia typically occurred during Cycle 1. Ocular adverse events (e.g., corneal epitheliopathy, dry eye) were reported for 57% of patients treated Q3Wk and were generally reversible. Antitumor activity in patients treated Q3Wk included 1 complete response, 2 partial responses, and 20 stable disease. SGN-75 exposures were approximately dose proportional, with a mean terminal half-life of 10 days. Substantial depletions of CD70-positive peripheral blood lymphocytes were observed after SGN-75 treatment. CONCLUSIONS: Modest single-agent activity and generally manageable adverse events were observed in heavily pretreated RCC and NHL patients. Administration Q3Wk was better tolerated than weekly dosing. Targeted ablation of CD70-positive lymphocytes was demonstrated. PMID- 25142261 TI - Prospective analysis of the accuracy of diagnosis of carpal tunnel syndrome using a web-based questionnaire. AB - OBJECTIVE: To confirm the accuracy of a diagnostic questionnaire for carpal tunnel syndrome (CTS) when presented via a public website rather than on paper. DESIGN: Prospective comparison of the probability of CTS as assessed by the web based questionnaire at http://www.carpal-tunnel.net with the results of nerve conduction studies. SETTING: Subregional neurophysiology laboratory serving a population of 700,000 in East Kent, UK. PARTICIPANTS: 2821 individuals who were able to complete an online diagnostic questionnaire out of 4899 referred for initial diagnostic testing for new presentations with suspected CTS from April 2011 to March 2013. No exclusions were made on grounds of age, gender or coincident pathology. Main outcome measure--nerve conduction results confirming CTS. The severity of median nerve impairment demonstrated was also assessed using a validated neurophysiological scale. RESULTS: The web-based questionnaire accurately estimates the probability of CTS being confirmed on nerve conduction studies. Using a website diagnostic score of >=40% as an example cut-off value the questionnaire achieves 78% sensitivity and 68% specificity in predicting the finding of evidence of CTS on nerve conduction studies. The web-based version of the diagnostic questionnaire was as accurate as the original paper version with an area under the receiver operating characteristic curve of 0.79. There was also a significant correlation between the diagnostic score given by the website and the severity of CTS with higher scores being associated with greater nerve dysfunction (r=0.3, p<0.00001). CONCLUSIONS: Completion of the symptom questionnaire on the website by patients at home provides a prediction of the likelihood of CTS which is sufficiently accurate to be used in initial planning of investigation and treatment. PMID- 25142262 TI - The effects of financial incentives for case finding for depression in patients with diabetes and coronary heart disease: interrupted time series analysis. AB - OBJECTIVE: To evaluate the effects of Quality and Outcomes Framework (QOF) incentivised case finding for depression on diagnosis and treatment in targeted and non-targeted long-term conditions. DESIGN: Interrupted time series analysis. SETTING: General practices in Leeds, UK. PARTICIPANTS: 65 (58%) of 112 general practices shared data on 37,229 patients with diabetes and coronary heart disease targeted by case finding incentives, and 101,008 patients with four other long term conditions not targeted (hypertension, epilepsy, chronic obstructive pulmonary disease and asthma). INTERVENTION: Incentivised case finding for depression using two standard screening questions. MAIN OUTCOME MEASURES: Clinical codes indicating new depression-related diagnoses and new prescriptions of antidepressants. We extracted routinely recorded data from February 2002 through April 2012. The number of new diagnoses and prescriptions for those on registers was modelled with a binomial regression, which provided the strength of associations between time periods and their rates. RESULTS: New diagnoses of depression increased from 21 to 94/100,000 per month in targeted patients between the periods 2002-2004 and 2007-2011 (OR 2.09; 1.92 to 2.27). The rate increased from 27 to 77/100,000 per month in non-targeted patients (OR 1.53; 1.46 to 1.62). The slopes in prescribing for both groups flattened to zero immediately after QOF was introduced but before incentivised case finding (p<0.01 for both). Antidepressant prescribing in targeted patients returned to the pre-QOF secular upward trend (Wald test for equivalence of slope, z=0.73, p=0.47); the slope was less steep for non-targeted patients (z=-4.14, p<0.01). CONCLUSIONS: Incentivised case finding increased new depression-related diagnoses. The establishment of QOF disrupted rising trends in new prescriptions of antidepressants, which resumed following the introduction of incentivised case finding. Prescribing trends are of concern given that they may include people with mild-to-moderate depression unlikely to respond to such treatment. PMID- 25142263 TI - Peripheral labour market position and risk of disability pension: a prospective population-based study. AB - OBJECTIVE: To investigate what impact individuals' position in a labour market core-periphery structure may have on their risk of disability pension (DP) in general and specifically on their risk of DP based on mental or musculoskeletal diagnoses. METHODS: The study comprised 45,567 individuals who had been interviewed for the annual Swedish Surveys of Living Conditions (1992-2007). The medical DP diagnoses were obtained from the Swedish Social Insurance Agency (1993 2011). The assumed predictors were studied in relation to DP by Cox's proportional hazards regression. The analyses were stratified on sex and age, controlling for social background and self-reported long-standing illness at baseline. RESULTS: All three indicators underlying the categorisation of the core periphery structure: employment income, work hours and unemployment, increased the risk of DP in all strata. The risk of DP tended to increase gradually the more peripheral the labour market position was. The risk estimates for DP in general and for DP based on mental diagnoses were particularly high among men aged 20-39 years. CONCLUSIONS: The core-periphery position of individuals, representing their labour market attachment, was found to be a predictor of future DP. The association was most evident among individuals below 40 years of age with regard to DP based on mental diagnoses. This highlights the need for preventative measures that increase the participation of young people in working life. PMID- 25142265 TI - Acupuncture for patients with Alzheimer's disease: a systematic review protocol. AB - INTRODUCTION: The aim of this protocol is to provide the methods used to assess the effectiveness and safety of acupuncture for the treatment of patients with Alzheimer's disease. METHODS AND ANALYSIS: We will search the following electronic databases: The Cochrane Library, PubMed, Medline, Embase, PsycINFO, Chinese Biomedical Literature Database, Chinese Medical Current Contents and China National Knowledge Infrastructure without restriction of language and publication status. Other sources such as Chinese acupuncture journals and the reference list of selected studies will also be searched. After screening the studies, a meta-analysis of randomised controlled trials will be conducted, if possible. Results expressed as risk ratios for dichotomous data and standardised or weighted mean differences for continuous data, will be used for data synthesis. DISSEMINATION: The protocol of this systematic review will be disseminated in a peer-reviewed journal and presented at a relevant conference. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014009619. PMID- 25142264 TI - Risk factors for suicidal thoughts in adolescence--a prospective cohort study: the Young-HUNT study. AB - OBJECTIVES: Examining the associations between health and lifestyle factors recorded in the participants' early teens and development of suicidal thoughts recorded 4 years later. DESIGN: Population-based prospective cohort study. SETTINGS: All students in the two relevant year classes in Nord-Trondelag County were invited, 80% attended both waves of data collection. PARTICIPANTS: 2399 secondary school students who participated in the Young-HUNT1 study in 1995-1997 (13-15 years old) were included in a follow-up study 4 years later (17-19 years old). PRIMARY OUTCOME MEASURE: Suicidal thoughts reported at age 17-19 years. RESULTS: 408 (17%, 95% CI 15.5% to 18.5%) of the adolescents reported suicidal thoughts at follow-up, 158 (14.2%, CI 13.6% to 16.4%) boys and 250 (19.5%, CI 18.8% to 22.0%) girls. Baseline anxiety and depressive symptoms (adjusted OR (aOR) 1.9, CI 1.4 to 2.6), conduct problems (aOR 1.8, CI 1.3 to 2.6), overweight (aOR 1.9 CI 1.4 to 2.4), and muscular pain and tension (aOR 1.8, CI 1.4 to 2.4), were all associated with reporting suicidal thoughts at follow-up. CONCLUSIONS: One in six young adults experienced suicidal thoughts, girls predominating. Suicidal thoughts were most strongly associated with symptoms of anxiety/depression, conduct problems, pain/tension and overweight reported when participants were 13-15 years old. Specific preventive efforts in these groups might be indicated. Future research should investigate whether similar associations are seen with suicide/suicidal attempts as endpoints. PMID- 25142266 TI - Mapping the protein profile involved in the biotransformation of organoarsenicals using an arsenic metabolizing bacterium. AB - Alkaliphilus oremlandii strain OhILAs, a gram-positive bacterium, has been shown to ferment lactate as well as use arsenate and roxarsone as a terminal electron acceptor. This study examines the proteome expressed under four growth conditions to further elucidate the bacterial metabolism of inorganic and organic arsenic. The four growth conditions include, sodium lactate (as fermentative control), sodium lactate with 3-nitro-4-hydroxybenzenearsonic acid (roxarsone), sodium lactate with 3-amino-4-hydroxybenzenearsonic acid (3A4HBAA), and sodium lactate with sodium arsenate. Shotgun proteomics using LC-MS/MS was performed on the soluble cytoplasm as well as solubilized membrane proteins using perfluorooctanoic acid, a surfactant with properties similar to sodium dodecyl sulfate. The MS/MS data were analyzed using the Spectrum Mills Proteomic Workbench. Positive protein matches were confirmed with protein scores of 20 or greater and the presence of two or more peptides among the three technical replicates. A total of 1357 proteins (out of 2836 predicted) were identified with 791 in sodium lactate, 816 in sodium lactate and roxarsone, 715 in sodium lactate and 3A4HBAA, and 733 in sodium lactate and arsenate. The relative abundance of each protein was determined using a method called normalized spectral abundance factor (NSAF). Proteins that were identified in both the control and the experimental conditions were compared using the Power Law Global Error Model (PLGEM) to determine proteins that were significantly up or down regulated. All putative proteins were assigned functions and pathways using the COG databases. However, a large number of proteins were classified as hypothetical or had unknown function. Using the statistical information and known functionalities of the identified proteins, a pathway for the degradation of roxarsone and 3A4HBAA by A. oremlandii strain OhILAs is proposed. PMID- 25142267 TI - Assessment of tibial rotation and meniscal movement using kinematic magnetic resonance imaging. AB - OBJECTIVE: This work aimed to assess tibial rotations, meniscal movements, and morphological changes during knee flexion and extension using kinematic magnetic resonance imaging (MRI). METHODS: Thirty volunteers with healthy knees were examined using kinematic MRI. The knees were imaged in the transverse plane with flexion and extension angles from 0 degrees to 40 degrees and 40 degrees to 0 degrees , respectively. The tibial interior and exterior rotation angles were measured, and the meniscal movement range, height change, and side movements were detected. RESULTS: The tibia rotated internally (11.55 degrees +/- 3.20 degrees ) during knee flexion and rotated externally (11.40 degrees +/- 3.0 degrees ) during knee extension. No significant differences were observed between the internal and external tibial rotation angles (P > 0.05), between males and females (P > 0.05), or between the left and right knee joints (P > 0.05). The tibial rotation angle with a flexion angle of 0 degrees to 24 degrees differed significantly from that with a flexion angle of 24 degrees to 40 degrees (P < 0.01). With knee flexion, the medial and lateral menisci moved backward and the height of the meniscus increased. The movement range was greater in the anterior horn than in the posterior horn and greater in the lateral meniscus than in the medial meniscus (P < 0.01). During backward movements of the menisci, the distance between the anterior and posterior horns decreased, with the decrease more apparent in the lateral meniscus (P < 0.01). The side movements of the medial and lateral menisci were not obvious, and a smaller movement range was found than that of the forward and backward movements. CONCLUSION: Knee flexion and extension facilitated internal and external tibial rotations, which may be related to the ligament and joint capsule structure and femoral condyle geometry. PMID- 25142269 TI - High speed all optical Nyquist signal generation and full-band coherent detection. AB - Spectrum efficient data transmission is of key interest for high capacity optical communication systems considering the limited available bandwidth. Transmission of the high speed signal with higher-order modulation formats within the Nyquist bandwidth using coherent detection brings attractive performance advantages. However, high speed Nyquist signal generation with high order modulation formats is challenging. Electrical Nyquist pulse generation is restricted by the limited sampling rate and processor capacities of digital-to-analog convertor devices, while the optical Nyquist signals can provide a much higher symbol rate using time domain multiplexing method. However, most optical Nyquist signals are based on direct detection with simple modulation formats. Here we report the first experimental demonstration of high speed all optical Nyquist signal generation based on Sinc-shaped pulse generation and time-division multiplexing with high level modulation format and full-band coherent detection. Our experiments demonstrate a highly flexible and compatible all optical high speed Nyquist signal generation and detection scheme for future fiber communication systems. PMID- 25142268 TI - New-onset psychiatric disorders after corticosteroid therapy in systemic lupus erythematosus: an observational case-series study. AB - The objective of this study was to clarify the incidence, clinical characteristics, and courses of new-onset psychiatric manifestations after corticosteroid therapy in patients with systemic lupus erythematosus (SLE), including possible ways of differentiating between corticosteroid-induced psychiatric disorders (CIPDs) and central nervous system manifestations of SLE (CNS-SLE). We prospectively followed for 8 weeks 139 consecutive episodes in 135 in-patients who had a non-CNS-SLE flare treated with corticosteroids. Psychiatric events were evaluated once a week using DSM-IV criteria. We then conducted a post hoc etiological analysis of any newly developed psychiatric events during this follow-up period. In the 8 weeks of corticosteroid administration, new psychiatric events occurred in 20 (14.4 %) of the 139 episodes. The mean dosage of corticosteroids administered was prednisolone at 0.98 (range 0.24-1.39) mg/kg/day. Of the 20 psychiatric events, 14 (10.1 %) were suitable for the strict definition of CIPDs, accompanied by mood disorders in 13 (depressive in 2, manic in 9, and mixed in 2) and psychotic disorder in one. Two (1.4 %), both presenting delirium, were diagnosed as CNS-SLE on the basis of evidence of abnormal CNS findings even before psychiatric manifestations, all of which improved in parallel with these patients' recoveries through augmentation of immunosuppressive therapy. The other four events (2.9 %) could not be etiologically identified. This study suggests that corticosteroid therapy triggers CIPDs and CNS-SLE in patients with SLE. Delirium may be suggestive of CNS-SLE, while mood disorders may be more suggestive of CIPDs. Electroencephalographic abnormalities may possibly be predictive of CNS-SLE. PMID- 25142270 TI - Enteral ecoimmunonutrition reduced enteral permeability and serum ghrelin activity in severe cerebral stroke patients with lung infection. AB - The study analyzed how enteral ecoimmunonutrition, which comprises probiotics, glutamine, fish oil, and Enteral Nutritional Suspension (TPF), can impact on the enteral permeability and serum Ghrelin activity in severe cerebral stroke patients with lung infection. Among 190 severe cerebral stroke patients with tolerance to TPF, they were randomized into control and treatment groups after antibiotics treatment due to lung infections. There were 92 patients in the control group and 98 patients in treatment group. The control group was treated with TPF and the treatment group was treated with enteral ecoimmunonutrition, which comprises probiotics, glutamine, fish oil, and Enteral Nutritional Suspension. All patients received continuous treatments through nasoenteral or nasogastric tubes. 7, 14, and 21 days after the treatments, the enteral tolerance to nutrition was observed in both groups. The tests included abdominal pain, bloating, diarrhea, and lactulose/mannitol (L/M) ratio. Serum Ghrelin levels were determined by ELISA. The incidence of abdominal pain, bloating, diarrhea was lower in the treatment group and enteral tolerance to nutrition was also superior to the control group. No difference in serum Ghrelin level was observed between the control and treatment groups with enteral intolerance to nutrition. However, in patients with enteral tolerance to nutrition, the treatment group showed lower enteral nutrition and lower enteral permeability compared to the control group. In severe cerebral stroke patients with lung infection, enteral ecoimmunonutrition after antibiotics treatment improved enteral tolerance to nutrition and reduced enteral permeability; meanwhile, it lowered the serum Ghrelin activity, which implied the high serum Ghrelin reduces enteral permeability. PMID- 25142271 TI - Distal femoral osteotomy. AB - Osteotomies around the knee are well-recognized treatments for unloading the affected compartment in cases of lower limb malalignment. There are few papers in the literature describing the outcomes of distal femoral osteotomy (DFO), as compared with the studies reporting on high tibial osteotomy (HTO), probably because valgus malalignment is less common than the varus one. There is still debate as to what the correct indication is and which surgical techniques lead to the best outcomes in performing a DFO. Besides, it is still controversial whether patellofemoral arthritis should be considered as a contraindication to performing a DFO, as well as in HTO. In this article, we will summarize the indications for DFO, the surgical techniques reported in the literature, and their outcomes. PMID- 25142272 TI - Efficient Calibration/Uncertainty Analysis Using Paired Complex/Surrogate Models. AB - The use of detailed groundwater models to simulate complex environmental processes can be hampered by (1) long run-times and (2) a penchant for solution convergence problems. Collectively, these can undermine the ability of a modeler to reduce and quantify predictive uncertainty, and therefore limit the use of such detailed models in the decision-making context. We explain and demonstrate a novel approach to calibration and the exploration of posterior predictive uncertainty, of a complex model, that can overcome these problems in many modelling contexts. The methodology relies on conjunctive use of a simplified surrogate version of the complex model in combination with the complex model itself. The methodology employs gradient-based subspace analysis and is thus readily adapted for use in highly parameterized contexts. In its most basic form, one or more surrogate models are used for calculation of the partial derivatives that collectively comprise the Jacobian matrix. Meanwhile, testing of parameter upgrades and the making of predictions is done by the original complex model. The methodology is demonstrated using a density-dependent seawater intrusion model in which the model domain is characterized by a heterogeneous distribution of hydraulic conductivity. PMID- 25142273 TI - C-H bond activation and S-atom transfer from cobalt(III) thiolate and isothiocyanate complexes. AB - The cobalt phenylthiolate complex, cis,mer-(PMe3)3Co(CH3)2SPh, was found to undergo competitive two-electron ethane reductive elimination and C-H bond cyclometallation. The thiophenolato bound cobaltacycle was generated via C-H bond oxidative addition to a five-coordinate intermediate followed by rapid methane elimination. A related cobalt isothiocyanate complex, cis,mer-(PMe3)3Co(CH3)2NCS, was also prepared and found to perform ethane elimination and S-atom transfer to yield trimethylphosphine sulfide. This rare example of S-atom donation from a isothiocyanate was characterized by NMR and GC-MS analysis, with cis,mer (PMe3)3Co(CH3)2CN identified as one of the cobalt based products. PMID- 25142274 TI - Effectiveness of tongue-tie division for speech disorder in children. AB - BACKGROUND: The aim of this study was to determine the effectiveness of tongue tie division (frenuloplasty/ frenulotomy) for speech articulation disorder in children with ankyloglossia (tongue-tie). METHODS: Articulation test was done in five children (3-8 years old) with speech problems who underwent tongue-tie division. The test consisted of 50 pictures of common Japanese words with 2-3 syllables. The patients were interviewed by a speech therapist and asked to pronounce what the picture card showed. Misarticulations of substitution, omission, and distortion were assessed. The preoperative results were compared with postoperative examinations at 1 month, 3-4 months, and 1-2 years. RESULTS: Nineteen substitutions that were observed in four patients preoperatively decreased to 10 in three patients at 1 month, 7 in three patients at 3-4 months, and 1 in one patient at 1-2 years postoperatively. Five omissions that were observed in four patients preoperatively decreased to 3 in three patients at 1 month, 2 in two patients at 3-4 months, and 1 in one patient at 1-2 years postoperatively. Thirteen distortions that were observed in five patients preoperatively decreased to 8 in four patients at 3-4 months but increased to 11 in three patients at 1-2 years postoperatively. CONCLUSIONS: Substitution and omission improved relatively early after tongue-tie division and progressed to distortion, which is a less-impaired form of articulation disorder. Thus, distortion required more time for improvement and remained a defective speaking habit in some patients. PMID- 25142275 TI - Is plasminogen activator inhibitor type 2 really a plasminogen activator inhibitor after all? PMID- 25142276 TI - A randomized comparison of energy consumption when using different canes, inpatients after stroke. AB - OBJECTIVES: To investigate the differences in oxygen consumption associated with gait in hemiplegic patients according to the type of cane they use. DESIGN: A randomized crossover design. SETTING: University hospital-based rehabilitation center, Korea. SUBJECTS: Thirty consecutive patients (mean +/- SD age, 56.3 +/- 3.2 years) with chronic stroke, 17 (56.7%) males and 13 (43.3%) females. INTERVENTIONS: At approximately the same time of day for three consecutive days, each participant completed a walk with one of three randomly assigned types of canes: a single-point cane, a quad cane, and a hemi-walker. MAIN OUTCOME MEASURE: Energy expenditure (O2 rate, mL/kg/min), energy cost (O2 cost, mL/kg/m), and heart rate (HR) via a portable gas analyzer, a 10-meter walk test (10MWT), and a 6-minute walk test (6MWT). RESULTS: Energy expenditure, gait endurance, and gait velocity for a single-point cane were higher (p<0.001 or p=0.005) than for any other type of cane. Energy cost (0.5 +/- 0.2 mL/kg/m vs. 0.6 +/- 0.2 mL/kg/m vs. 0.6 +/- 0.2 ml/kg/m, respectively, p=0.001) was lower for the single-point cane, except for HR (p >= 0.05) after the Bonferroni correction (0.05/5=0.01). CONCLUSIONS: A single-point cane requires less oxygen use at a given speed, or permits greater speed for the same oxygen consumption. PMID- 25142277 TI - Balance training with multi-task exercises improves fall-related self-efficacy, gait, balance performance and physical function in older adults with osteoporosis: a randomized controlled trial. AB - OBJECTIVE: To evaluate the effects of a balance training program including dual- and multi-task exercises on fall-related self-efficacy, fear of falling, gait and balance performance, and physical function in older adults with osteoporosis with an increased risk of falling and to evaluate whether additional physical activity would further improve the effects. DESIGN: Randomized controlled trial, including three groups: two intervention groups (Training, or Training+Physical activity) and one Control group, with a 12-week follow-up. SETTING: Stockholm County, Sweden. PARTICIPANTS: Ninety-six older adults, aged 66-87, with verified osteoporosis. INTERVENTIONS: A specific and progressive balance training program including dual- and multi-task three times/week for 12 weeks, and physical activity for 30 minutes, three times/week. MAIN MEASURES: Fall-related self efficacy (Falls Efficacy Scale-International), fear of falling (single-item question - 'In general, are you afraid of falling?'), gait speed with and without a cognitive dual-task at preferred pace and fast walking (GAITRite(r)), balance performance tests (one-leg stance, and modified figure of eight), and physical function (Late-Life Function and Disability Instrument). RESULTS: Both intervention groups significantly improved their fall-related self-efficacy as compared to the controls (p <= 0.034, 4 points) and improved their balance performance. Significant differences over time and between groups in favour of the intervention groups were found for walking speed with a dual-task (p=0.003), at fast walking speed (p=0.008), and for advanced lower extremity physical function (p=0.034). CONCLUSIONS: This balance training program, including dual- and multi-task, improves fall-related self-efficacy, gait speed, balance performance, and physical function in older adults with osteoporosis. PMID- 25142278 TI - Exercise testing and training in people with Huntington's disease. AB - OBJECTIVE: To explore exercise response in people with Huntington's disease (HD). DESIGN: Experimental observational study with a randomly allocated subgroup before/after interventional study. SETTING: Community. SUBJECTS: People with HD (n=30) and a healthy comparator group (n=20). Thirteen people from the HD group were randomly allocated to an exercise training program. MAIN MEASURES: Heart rate (HR) and perceived exertion on the Borg-CR10 scale (RPE) during a submaximal cycle ergometer exercise test (three minute unloaded and nine minute 65% 75%HRmaximum phase). Expired air and lactate measures were available for 8 people with HD during the exercise. INTERVENTION: A 12 week gym and home walking exercise programme (n=13). RESULTS: People with HD achieved a lower work rate at nine minutes (82+/-42(0-195) v 107+/-35(50 -185) Watts (p<0.05)), but higher RPE at both three (3+/-2(0-7) v 1+/-1(0-4)) and nine minutes (7+/-3(1-10) v 5+/- 2(2 9)) both p<0.01, compared to the healthy group and did not achieve a steady state HR during unloaded cycling. People with HD also demonstrated higher than expected lactate at three 2.5+/-2.5(1.1-8)mmo.L-1 and nine 3.8+/-1.9(1.2-6.6)mmo.L-1 minutes and respiratory exchange ratio at three 0.78+/-0.03 (0.74-0.81) and nine minutes 0.94+/-0.11(0.81-1.15). After exercise training there were no changes observed in HR or RPE responses during the exercise test. CONCLUSIONS: There was a large variability in the observed metabolic and physiological responses to exercise in people with HD. The observed exercise responses suggest that altered exercise prescription parameters may be required for people with HD and that exercise response and factors' affecting this requires further investigation. PMID- 25142279 TI - Narrative therapy an evaluated intervention to improve stroke survivors' social and emotional adaptation. AB - OBJECTIVE: To describe a theoretical and practical framework of using a train metaphor in narrative therapy for stroke rehabilitation in group practice. BACKGROUND: There is a paucity of literature on the application of narrative therapy in meeting the psycho-social-spiritual needs of stroke survivors in rehabilitation. In the current article, the use of narrative therapy being evaluated in a formal randomized study in stroke survivors is described in detail. The metaphor may be of practical interest to those working with populations confronted with unpredictable life challenges. METHOD: Narrative practice using the metaphor of 'Train of life' is an alternative practice to psychopathology, which provides a means for the participants to deconstruct from the illness experience, re-author their lives, and reconstruct their identity with hopes and dreams. This therapeutic conversations, primarily using questions, can be divided into six steps: (1) engaging participants to a Concord station; (2) unfolding the experience with Stroke: where each of the participants are coming from; (3) dialoging directly with Stroke; (4) co-constructing the train carriage; (5) planning for a future life journey with Stroke; and (6) celebrating the unlocking of a new journey. Along with the train of life metaphor, therapeutic documents and outsider witness conversations are used to strengthen the preferred identity, as opposed to the problem-saturated identity of the participants. DISCUSSION: This metaphor poses an alternative methodology in stroke rehabilitation by reconnecting the survivors' inner resources, skills, and competencies. Eventually, it could re-author the survivors' identity developed from previous life challenges and reconstruct their purpose in life. PMID- 25142280 TI - Does pelvic floor muscle training abolish symptoms of urinary incontinence? A randomized controlled trial. AB - OBJECTIVE: To determine whether symptoms of urinary incontinence is reduced by pelvic floor muscle training, to determine whether urinary incontinence can be totally eliminated by strengthening the pelvic floor muscle to grade 5 on the Oxford scale. DESIGN: Prospective randomized controlled clinical trial. SETTING: Outpatient urogynecology department. SUBJECTS: One hundred thirty cases with stress and mixed urinary incontinence. INTERVENTION: All participants were randomly allocated to the pelvic floor muscle training group or control group. A 12-week home based exercise program, prescribed individually, was performed by the pelvic floor muscle training group. MAIN MEASURES: Urinary incontinence symptoms (Incontinence Impact Questionnaire-7, Urogenital Distress Inventory-6, bladder diary, stop test and pad test) were assessed, and the pelvic floor muscle strength was measured for (PERFECT testing, perineometric and ultrasound) all participants before and after 12 weeks of treatment. RESULTS: The pelvic floor muscle training group had significant improvement in their symptoms of urinary incontinence (P=0.001) and an increase in pelvic floor muscle strength (P=0.001, by the dependent t test) compared with the control group. All the symptoms of urinary incontinence were significantly decreased in the patients that had reached pelvic floor muscle strength of grade 5 and continued the pelvic floor muscle training (P<0.05). CONCLUSION: The study demonstrated that pelvic floor muscle training is effective in reducing the symptoms of stress and mixed urinary incontinence and in increasing pelvic floor muscle strength. PMID- 25142281 TI - Successful treatment of a patient with ventriculoperitoneal shunt-associated meningitis caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae. AB - Bacterial meningitis is responsible for significant morbidity and mortality worldwide, despite that modern antibiotics effectively penetrate cerebrospinal fluid to eradicate bacteria. A clinical suspicion of bacterial meningitis should be recognized early for the rapid diagnostic workup. Bacterial meningitis associated with ventriculoperitoneal shunt (VPS) is not uncommon and infrequently presents as abdominal symptoms and signs. Infections of the central nervous system caused by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) are extremely rare, and such multiple drug-resistant pathogens frequently cause inappropriate treatments and mortality. beta-Lactamases are bacterial enzymes that inactivate beta-lactam antimicrobial agents. The increased prevalence of ESBL-producing organism infections has become a worldwide problem. Timely and appropriate treatment is important to reduce mortality and morbidity of infections caused by ESBL-producing organisms. Here, we report a 61-year-old male patient who underwent VPS implantation for consequent hydrocephalus following spontaneous intracranial hemorrhage six months before this presentation. He was admitted for intermittent fever and right lower quadrant abdominal pain, and he was initially managed as acute appendicitis with its typical presentation. Finally, he was diagnosed VPS-associated meningitis caused by ESBL-KP. This patient was successfully treated with the combination of meropenem, a carbapenem antibiotic that is the drug of choice for treating ESBL producing organisms, and high-dose fosfomycin, a phosphonic acid derivative antibiotic that is effective in treating some drug-resistant pathogens. In the present report, we emphasize the clinical presentations of catheter-related meningitis and risk factors for infections caused by ESBL-producing pathogens. Antibiotic combination therapy can provide synergistic effect and maximize anti bacterial activity in ESBL-KP meningitis. PMID- 25142282 TI - Distribution of ether lipids and composition of the archaeal community in terrestrial geothermal springs: impact of environmental variables. AB - Archaea can respond to changes in the environment by altering the composition of their membrane lipids, for example, by modification of the abundance and composition of glycerol dialkyl glycerol tetraethers (GDGTs). Here, we investigated the abundance and proportions of polar GDGTs (P-GDGTs) and core GDGTs (C-GDGTs) sampled in different seasons from Tengchong hot springs (Yunnan, China), which encompassed a pH range of 2.5-10.1 and a temperature range of 43.7 93.6 degrees C. The phylogenetic composition of the archaeal community (reanalysed from published work) divided the Archaea in spring sediment samples into three major groups that corresponded with spring pH: acidic, circumneutral and alkaline. Cluster analysis showed correlation between spring pH and the composition of P- and C-GDGTs and archaeal 16S rRNA genes, indicating an intimate link between resident Archaea and the distribution of P- and C-GDGTs in Tengchong hot springs. The distribution of GDGTs in Tengchong springs was also significantly affected by temperature; however, the relationship was weaker than with pH. Analysis of published datasets including samples from Tibet, Yellowstone and the US Great Basin hot springs revealed a similar relationship between pH and GDGT content. Specifically, low pH springs had higher concentrations of GDGTs with high numbers of cyclopentyl rings than neutral and alkaline springs, which is consistent with the predominance of high cyclopentyl ring-characterized Sulfolobales and Thermoplasmatales present in some of the low pH springs. Our study suggests that the resident Archaea in these hot springs are acclimated if not adapted to low pH by their genetic capacity to effect the packing density of their membranes by increasing cyclopentyl rings in GDGTs at the rank of community. PMID- 25142283 TI - Dissecting the mechanism of martensitic transformation via atomic-scale observations. AB - Martensitic transformation plays a pivotal role in the microstructural evolution and plasticity of many engineering materials. However, so far the underlying atomic processes that accomplish the displacive transformation have been obscured by the difficulty in directly observing key microstructural signatures on atomic scale. To resolve this long-standing problem, here we examine an AISI 304 austenitic stainless steel that has a strain/microstructure-gradient induced by surface mechanical attrition, which allowed us to capture in one sample all the key interphase regions generated during the gamma(fcc) -> epsilon(hcp) -> alpha'(bcc) transition, a prototypical case of deformation induced martensitic transformation (DIMT). High-resolution transmission electron microscopy (HRTEM) observations confirm the crucial role of partial dislocations, and reveal tell tale features including the lattice rotation of the alpha' martensite inclusion, the transition lattices at the epsilon/alpha' interfaces that cater the shears, and the excess reverse shear-shuffling induced gamma necks in the epsilon martensite plates. These direct observations verify for the first time the 50 year-old Bogers-Burgers-Olson-Cohen (BBOC) model, and enrich our understanding of DIMT mechanisms. Our findings have implications for improved microstructural control in metals and alloys. PMID- 25142284 TI - Survivorship, palliative care and quality of life. PMID- 25142285 TI - Stimulation of invariant natural killer T cells by alpha-Galactosylceramide activates the JAK-STAT pathway in endothelial cells and reduces angiogenesis in the 5T33 multiple myeloma model. AB - Tumour pathogenesis in multiple myeloma (MM) correlates with a high vascular index. Therefore, targeting angiogenesis is an important therapeutic tool to reduce MM progression. This study aimed to investigate the role of invariant natural killer T (iNKT) cells in angiogenesis and the mechanisms behind the stimulation by alpha-Galactosylceramide (alpha-GalCer). We have previously found that alpha-GalCer could increase the survival of 5T33MM mice and here we demonstrate that alpha-GalCer reduces the microvessel density. We performed both in vivo and in vitro angiogenic assays to confirm this observation. We found that conditioned medium of alpha-GalCer stimulated iNKT cells reduced neovascularization in the chick chorioallantoic membrane and in matrigel plug assays. Moreover, we observed a reduction in proliferation, migration and network formation and an induction of apoptosis upon exposure of murine endothelial cell lines to this conditioned medium. We furthermore observed that the JAK-STAT signaling pathway was highly activated in endothelial cells in response to stimulated iNKT cells, indicating the possible role of IFN-gamma in the anti angiogenic process. In conclusion, these results highlight the possibility of recruiting iNKT cells to target MM and angiogenesis. This gives a rationale for combining immunotherapy with conventional anti-tumour treatments in view of increasing their therapeutic potential. PMID- 25142286 TI - Service-learning's impact on dental students' attitude towards community service. AB - BACKGROUND: This study evaluated service-learning programme's impact on senior dental students' attitude towards community service at Virginia Commonwealth University (VCU) School of Dentistry. Experience gained through service-learning in dental school may positively impact dental students' attitude towards community service that will eventually lead into providing care to the underserved. MATERIALS AND METHODS: Two surveys (pre- and post-test) were administered to 105 senior dental students. For the first survey (post-test), seventy-six students of 105 responded and reported their attitude towards community service immediately after the service-learning programme completion. Three weeks later, 56 students of the 76 responded to the second survey (retrospective pre-test) and reported their recalled attitude prior to the programme retrospectively. RESULTS: A repeated-measure mixed-model analysis indicated that overall there was improvement between pre-test and post-test. Scales of connectedness, normative helping behaviour, benefits, career benefits and intention showed a significant pre-test and post-test difference. An association between attitude towards community service and student characteristics such as age, gender, ethnicity and volunteer activity was also examined. Only ethnicity showed an overall significant difference. White dental students appear to have a differing perception of the costs of community service. CONCLUSIONS: The service-learning programme at VCU School of Dentistry has positively impacted senior dental students' attitude towards community service. PMID- 25142287 TI - Improvement of facial affect recognition in children and adolescents with attention-deficit/hyperactivity disorder under methylphenidate. AB - INTRODUCTION AND HYPOTHESIS: Some authors draw a connection between the dopaminergic pathways and emotional perception. The present study is based on that association and addresses the question whether methylphenidate and the resulting amelioration of the disturbed dopamine metabolism lead to an improvement of the facial affect recognition abilities in children with attention deficit/hyperactivity disorder (ADHD). METHODS: A computer test was conducted on 21 participants, aged 7-14 years and with a diagnosis of ADHD - some with comorbid oppositional defiant disorder - conducted the FEFA (Frankfurt Test and Training of Facial Affect), a computer test to examine their facial affect recognition abilities. It consists of two subtests, one with faces and one with eye pairs. All participants were tested in a double-blind cross-over study, once under placebo and once under methylphenidate. RESULTS AND DISCUSSION: The collected data showed that methylphenidate leads to amelioration of facial affect recognition abilities, but not on a significant level. Reasons for missing significance may be the small sample size or the fact that there exists some overlapping in cerebral connections and metabolic pathways of the site of action of methylphenidate and the affected dopaminergic areas in ADHD. However, consistent with the endophenotype concept, certain gene locations of the dopaminergic metabolism as both an aetiological factor for ADHD and the deficient facial affect recognition abilities with these individuals were considered. Consulting current literature they were found to be not concordant. Therefore, we conclude that the lacking significance of the methylphenidate affect on facial affect recognition is based on this fact. PMID- 25142288 TI - Orally administered whole egg demonstrates antidepressant-like effects in the forced swimming test on rats. AB - OBJECTIVE: Several studies have reported that vegetarian diets are associated with a higher prevalence of major depression. Therefore, we hypothesised that the consumption of animal products, especially eggs, may have positive effects on mental health, especially on major depression, because a previous study reported that egg consumption produces numerous beneficial effects in humans. The purpose of the present study was to evaluate the effects of chronic whole-egg treatment on depression-like behaviours in Wistar rats, a control strain, and Wistar Kyoto rats, an animal model of depression. METHODS: In both the rats, either whole-egg solution (5 ml/kg) or distilled water (5 ml/kg) was orally administrated for 35 days. During these periods, the open-field test (OFT) was conducted on the 21st day, and a forced swimming test (FST) was enforced on the 27th and 28th days. On the 36th day, the plasma and brain were collected. RESULTS: Chronic whole-egg treatment did not affect line crossing in the OFT, whereas it reduced the total duration of immobility in the FST on both strains. Furthermore, interestingly, the results indicated the possibility that whole-egg treatment elevated the incorporation of tryptophan into the brain, and the tryptophan concentration in the prefrontal cortex was actually increased by the treatment. CONCLUSION: This study demonstrated that whole-egg treatment exerts an antidepressant-like effect in the FST. It is suggested that whole egg may be an excellent food for preventing and alleviating the conditions of major depression. PMID- 25142289 TI - Optimal interval for hot water immersion tail-flick test in rats. AB - BACKGROUND: The hot water tail-flick test is widely used to measure the degree of nociception experienced by laboratory animals. This study was carried out to optimise interval times for the hot water immersion tail-flick tests in rats. METHOD: Ten different intervals from 10 s to 1 h were tested in 60 Sprague-Dawley male rats. At least eight rats were tested for each interval in three consecutive hot water tail-flick tests. Dixon's up-and-down method was also used to find the optimal intervals. The same rats were then divided into two groups. In Group N, naloxone was injected to reverse the prolonged latency times, whereas saline was used in the control Group S. RESULTS: Intervals of 10 s, 20 s, 30 min and 1 h did not significantly impact latencies, yielding similar results in three consecutive tests (p > 0.05). However, interval times of between 30 s and 20 min, inclusively, caused significantly prolonged latencies in the second and third tests (p < 0.001). Dixon's up-and-down method showed that 95% of the rats had prolonged latencies in hot water tail-flick tests at intervals longer than 32 s. Naloxone reversed prolonged latencies in Group N, whereas the latencies in Group S were further prolonged in 5 min interval tests. CONCLUSION: The optimal intervals for hot water tail-flick tests are either shorter than 20 s or longer than 20 min. The prolonged latencies after repetitive tests were attributable to an endocrine opioid. PMID- 25142290 TI - BDNF and S100B in psychotic disorders: evidence for an association with treatment responsiveness. AB - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) and S100B are involved in brain plasticity processes and their serum levels have been demonstrated to be altered in patients with psychoses. This study aimed to identify subgroups of patients with psychotic disorders across diagnostic boundaries that show a specific symptom profile or response to treatment with antipsychotics, by measuring serum levels of BDNF and S100B. METHODS: The study sample consisted of 58 patients with DSM-IV psychotic disorders. Comprehensive Assessment of Symptoms and History (CASH), Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression scale for severity and improvement (CGI-S/CGI-I) were applied at baseline and after 6 weeks of antipsychotic treatment. At both time points, serum levels of BDNF and S100B were measured and compared with a matched control sample. RESULTS: Baseline BDNF and S100B levels were significantly lower in patients as compared with controls and did not change significantly during treatment. Dividing the patient sample according to baseline biochemical parameters (low and high 25% and middle 50%), no differences in symptom profiles or outcome were found with respect to BDNF. However, the subgroups with low and high S100B levels had higher PANSS scores than the middle subgroup. In addition, the high subgroup still showed significantly more negative symptoms after treatment, whereas the low subgroup showed more positive symptoms compared with the other subgroups. CONCLUSION: Serum levels of BDNF and S100B are lowered in patients with psychotic disorders across diagnostic boundaries. The differences between high and low S100B subgroups suggest a relationship between S100B, symptom dimensions and treatment response, irrespective of diagnostic categories. PMID- 25142291 TI - Psychiatric side effects of ketamine in hospitalized medical patients administered subanesthetic doses for pain control. AB - OBJECTIVE: To assess the psychiatric side effects of ketamine when administered in subanesthetic doses to hospitalized patients. It is hypothesized that such effects occur frequently. METHODS: In this retrospective study, the medical records of 50 patients hospitalized on medical and surgical units at our facility who had continuous intravenous infusions of ketamine for pain or mild sedation were reviewed. Patient progress in the days following the start of ketamine infusion was reviewed and response to ketamine was noted. RESULTS: Twenty-two percent of the patients were noted to have some type of psychiatric reaction to ketamine, including agitation, confusion, and hallucinations. These reactions were relatively short lived, namely, occurring during or shortly after the infusions. No association was found between patient response to ketamine and gender, age, or infusion rate. CONCLUSION: Awareness of the psychiatric side effects of ketamine is an important consideration for clinicians administering this medication either for pain control or for depressive illness. PMID- 25142292 TI - A nationwide study on delirium in psychiatric patients from 1995 to 2011. AB - OBJECTIVES: Delirium shares symptoms with some mental illnesses. This may lead to misdiagnosis of delirium in psychiatric patients and a risk of inadequate management. Moreover, literature on delirium in psychiatric patients is sparse. The aim was to analyse possible changes in the diagnostic incidence of delirium in psychiatric patients from 1995 to 2011, and to investigate the patients with regard to sex, age, and type of patient. METHODS: All first time ever diagnoses of delirium among psychiatric patients were identified in the nationwide Danish Psychiatric Central Research Register (DPCRR) from 1995 to 2011. The delirium diagnoses include (1) delirium unspecified, (2) delirium with dementia, and (3) drug-related delirium, all in accordance with International Classification of Diseases-10. The incidence rates were age standardised. RESULTS: A total of 15 680 persons diagnosed with delirium for the first time were identified in the DPCRR between 1995 and 2011. The total incidence rate of delirium has decreased, reaching 8.4/1000 person-years in 2011. In 2011, 2.6% of the demented patients were diagnosed with delirium with dementia. Diagnosis of delirium is significantly more common in men, and the three groups of delirium showed a characteristic age distribution. CONCLUSION: Our incidences were markedly lower when compared with previous studies. This suggests a possible underdiagnosis of delirium in psychiatric hospitals and should be investigated further, as delirium is a serious state and identifying the syndrome is important for sufficient treatment. PMID- 25142293 TI - Association between the NOTCH4 gene rs3131296 polymorphism with schizophrenia risk in the Chinese Zhuang population and Chinese Han population. AB - BACKGROUND: Schizophrenia (SZ) is a common severe psychiatric disorder and a complex polygenic inherited disease that has not yet been fully interpreted. Heredity was proven to play an important role in the development of SZ. The association between the NOTCH4 gene rs3131296 polymorphism and SZ was reported to reach significance at the genome-wide level; therefore, it is necessary to replicate this association in other different populations. METHODS: To evaluate the association of the NOTCH4 gene rs3131296 polymorphism with the risk for SZ, and to explore whether a significant association could be replicated in different ethnic groups of China, we conducted this case-control study on 282 SZ cases (188 Han and 94 Zhuang) and 282 controls (188 Han and 94 Zhuang) among the Chinese Zhuang and Han populations. RESULTS: The results showed no statistically significant difference in the genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between SZ patients and healthy controls in either the Zhuang or Han samples (p > 0.05). In addition, no significant difference was found in genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between cases and controls in the combined samples including Zhuang and Han samples. CONCLUSIONS: Our study failed to replicate the significant association between the NOTCH4 gene rs3131296 polymorphism and the risk for SZ. PMID- 25142294 TI - Charting the decline in spontaneous writing in Alzheimer's disease: a longitudinal study. AB - OBJECTIVE: This study aims to document the nature and progression of the spontaneous writing impairment observed in patients with Alzheimer's disease (AD) over a 12-month period using both a cross-sectional and prospective longitudinal design. METHODS: Thirty-one minimal-moderate AD patients and 30 controls matched for age and socio-cultural background completed a simple and complex written description task at baseline. The AD patients then had follow-up assessments at 6 and 12 months. RESULTS: Cross-sectional comparisons indicated that minimal moderate AD patients produced more semantic paraphasias, phonological paraphasias, and empty and indefinite phrases, whilst producing fewer pictorial themes, repairing fewer errors, and producing shorter and less complex sentences than controls. The two groups could not be distinguished on visual paraphasias. Longitudinal follow-up, however, suggested that visual processing deteriorates over time, where the prevalence of visual errors increased over 12 months. Discussion The findings suggest that the deterioration of writing skills observed in the spontaneous writings of AD patients shows a pattern of impairment dominated by semantic errors with a secondary impairment in phonological processing, which is later joined by a disruption of visuospatial and graphomotor processing. PMID- 25142295 TI - Impaired recognition of happy facial expressions in bipolar disorder. AB - BACKGROUND: The ability to accurately judge facial expressions is important in social interactions. Individuals with bipolar disorder have been found to be impaired in emotion recognition; however, the specifics of the impairment are unclear. This study investigated whether facial emotion recognition difficulties in bipolar disorder reflect general cognitive, or emotion-specific, impairments. Impairment in the recognition of particular emotions and the role of processing speed in facial emotion recognition were also investigated. METHODS: Clinically stable bipolar patients (n = 17) and healthy controls (n = 50) judged five facial expressions in two presentation types, time-limited and self-paced. An age recognition condition was used as an experimental control. RESULTS: Bipolar patients' overall facial recognition ability was unimpaired. However, patients' specific ability to judge happy expressions under time constraints was impaired. CONCLUSIONS: Findings suggest a deficit in happy emotion recognition impacted by processing speed. Given the limited sample size, further investigation with a larger patient sample is warranted. PMID- 25142296 TI - Role of the medial prefrontal cortex in impaired decision making in juvenile attention-deficit/hyperactivity disorder. AB - IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) has been associated with deficient decision making and learning. Models of ADHD have suggested that these deficits could be caused by impaired reward prediction errors (RPEs). Reward prediction errors are signals that indicate violations of expectations and are known to be encoded by the dopaminergic system. However, the precise learning and decision-making deficits and their neurobiological correlates in ADHD are not well known. OBJECTIVE: To determine the impaired decision-making and learning mechanisms in juvenile ADHD using advanced computational models, as well as the related neural RPE processes using multimodal neuroimaging. DESIGN, SETTING, AND PARTICIPANTS: Twenty adolescents with ADHD and 20 healthy adolescents serving as controls (aged 12-16 years) were examined using a probabilistic reversal learning task while simultaneous functional magnetic resonance imaging and electroencephalogram were recorded. MAIN OUTCOMES AND MEASURES: Learning and decision making were investigated by contrasting a hierarchical Bayesian model with an advanced reinforcement learning model and by comparing the model parameters. The neural correlates of RPEs were studied in functional magnetic resonance imaging and electroencephalogram. RESULTS: Adolescents with ADHD showed more simplistic learning as reflected by the reinforcement learning model (exceedance probability, Px = .92) and had increased exploratory behavior compared with healthy controls (mean [SD] decision steepness parameter beta: ADHD, 4.83 [2.97]; controls, 6.04 [2.53]; P = .02). The functional magnetic resonance imaging analysis revealed impaired RPE processing in the medial prefrontal cortex during cue as well as during outcome presentation (P < .05, family-wise error correction). The outcome-related impairment in the medial prefrontal cortex could be attributed to deficient processing at 200 to 400 milliseconds after feedback presentation as reflected by reduced feedback-related negativity (ADHD, 0.61 [3.90] MUV; controls, -1.68 [2.52] MUV; P = .04). CONCLUSIONS AND RELEVANCE: The combination of computational modeling of behavior and multimodal neuroimaging revealed that impaired decision making and learning mechanisms in adolescents with ADHD are driven by impaired RPE processing in the medial prefrontal cortex. This novel, combined approach furthers the understanding of the pathomechanisms in ADHD and may advance treatment strategies. PMID- 25142297 TI - Facial Angiofibroma Severity Index (FASI): reliability assessment of a new tool developed to measure severity and responsiveness to therapy in tuberous sclerosis associated facial angiofibroma. AB - BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by the development of multisystem hamartomatous tumours. Topical sirolimus has recently been suggested as a potential treatment for TSC-associated facial angiofibroma (FA). AIM: To validate a reproducible scale created for the assessment of clinical severity and treatment response in these patients. METHODS: We developed a new tool, the Facial Angiofibroma Severity Index (FASI) to evaluate the grade of erythema and the size and extent of FAs. In total, 30 different photographs of patients with TSC were shown to 56 dermatologists at each evaluation. Three evaluations using the same photographs but in a different random order were performed 1 week apart. Test and retest reliability and interobserver reproducibility were determined. RESULTS: There was good agreement between the investigators. Inter-rater reliability showed strong correlations (> 0.98; range 0.97-0.99) with inter-rater correlation coefficients (ICCs) for the FASI. The global estimated kappa coefficient for the degree of intra-rater agreement (test-retest) was 0.94 (range 0.91-0.97). CONCLUSIONS: The FASI is a valid and reliable tool for measuring the clinical severity of TSC-associated FAs, which can be applied in clinical practice to evaluate the response to treatment in these patients. PMID- 25142298 TI - Endoscopic cystolithotomy by mini nephroscope: a preliminary study. AB - OBJECTIVE: To introduce a novel endoscopic surgical technique with mini nephroscope by suprapubic transvesical route for cystolithotripsy in children. MATERIAL AND METHODS: This was a non-randomized study with a series of 12 boys, between February 2012 and September 2013. Demographic, operative, and postoperative data were recorded. Our new endoscopic surgery technique could be performed in all patients. Complications were noted. RESULTS: Mean age was 35.1 +/- 8.6 months (19-46 months), the average stone size was 16.5 +/- 5.2 mm (10-20 mm). Mean operation time was 28.9 min (21-40), and mean hospital stay was 2.2 (2 3) days. In all procedures, stones were successfully fragmented and extracted by the new surgical technique. There was no intraoperative and/or postoperative complication or urethral stricture during follow-up period. In stone analyses, the main components were ammonium acid urate, calcium oxalate, and struvite. CONCLUSIONS: The new endoscopic surgery technique is safe and effective for bladder stones in children. Thus, our technique can be a strong candidate for an alternative treatment of childhood bladder stones. PMID- 25142299 TI - Highly conductive, capacitive, flexible and soft electrodes based on a 3D graphene-nanotube-palladium hybrid and conducting polymer. AB - Highly conductive, capacitive and flexible electrodes are fabricated by employing 3D graphene-nanotube-palladium nanostructures and a PEDOT:PSS conducting polymer. The fabricated flexible electrodes, without any additional metallic current collectors, exhibit increased charge mobility and good mechanical properties; they also allow greater access to the electrolyte ions and hence are suitable for flexible energy storage applications. PMID- 25142300 TI - IL-15-dependent CD8+ CD122+ T cells ameliorate experimental autoimmune encephalomyelitis by modulating IL-17 production by CD4+ T cells. AB - Interleukin-15 (IL-15) is an inflammatory cytokine whose role in autoimmune diseases has not been fully elucidated. Th17 cells have been shown to play critical roles in experimental autoimmune encephalomyelitis (EAE) models. In this study, we demonstrate that blockade of IL-15 signaling by TMbeta-1 mAb treatment aggravated EAE severity. The key mechanism was not NK-cell depletion but depletion of CD8+ CD122+ T cells. Adoptive transfer of exogenous CD8+ CD122+ T cells to TMbeta-1-treated mice rescued animals from severe disease. Moreover, transfer of preactivated CD8+ CD122+ T cells prevented EAE development and significantly reduced IL-17 secretion. Naive effector CD4+ CD25- T cells cultured with either CD8+ CD122+ T cells from wild-type mice or IL-15 transgenic mice displayed lower frequencies of IL-17A production with lower amounts of IL-17 in the supernatants when compared with production by effector CD4+ CD25- T cells cultured alone. Addition of a neutralizing antibody to IL-10 led to recovery of IL-17A production in Th17 cultures. Furthermore, coculture of CD8+ CD122+ T cells with effector CD4+ T cells inhibited their proliferation significantly, suggesting a regulatory function for IL-15 dependent CD8+ CD122+ T cells. Taken together, these observations suggest that IL-15, acting through CD8+ CD122+ T cells, has a negative regulatory role in reducing IL-17 production and Th17 mediated EAE inflammation. PMID- 25142301 TI - Synthesis and biological evaluation of glucosyl curcuminoids. AB - Medicinal plants proved to be a rich source in exploring a variety of lead structures in the development of new drugs. The natural curcuminoids have gained considerable attention in recent years for their multiple beneficial pharmacological and biological activities. Clinical application of these curcuminoids is often impaired due to their poor water solubility, resulting in low in vivo bioavailability of the active compound in humans. The objective of the present study is to synthesize glucosyl conjugates of curcumin 1 and tetrahydrocurcumin 4 and to evaluate their biological activities. The study highlights the synthesis of curcumin-beta-di-glucoside 3 (yield 71%) and tetrahydrocurcumin-beta-di-glucoside 6 (yield 64%) in good yields in a biphasic reaction medium using a phase transfer catalyst under simple and ecofriendly conditions. Both the glucosyl curcuminoids showed enhanced antioxidant, tyrosinase enzyme inhibitory, antimicrobial and potent cytotoxic activity. The improved biological activity may be due to the increased solubility of the glucosyl conjugated compounds compared to the native curcuminoids; this was further confirmed by partition coefficient studies. Thus, the synthesized glucosyl curcumin may serve as promising future therapeutic molecule in the management of cancer, whereas glucosyl tetrahydrocurcumin can be a useful ingredient in achromatic food and in cosmetic applications. PMID- 25142304 TI - Peritoneal milky spots serve as a hypoxic niche and favor gastric cancer stem/progenitor cell peritoneal dissemination through hypoxia-inducible factor 1alpha. AB - Peritoneal dissemination is the most common cause of death in gastric cancer patients. The hypoxic microenvironment plays a major role in controlling the tumor stem cell phenotype and is associated with patients' prognosis through hypoxia-inducible factor-1alpha (HIF-1alpha), a key transcriptional factor that responds to hypoxic stimuli. During the peritoneal dissemination process, gastric cancer stem/progenitor cells (GCSPCs) are thought to enter into and maintained in peritoneal milky spots (PMSs), which have hypoxic microenvironments. However, the mechanism through which the hypoxic environment of PMSs regulated GCSPC maintenance is still poorly understood. Here, we investigated whether hypoxic PMSs were an ideal cancer stem cell niche suitable for GCSPC engraftment. We also evaluated the mechanisms through which the HIF-1alpha-mediated hypoxic microenvironment regulated GCSPC fate. We observed a positive correlation between HIF-1alpha expression and gastric cancer peritoneal dissemination (GCPD) in gastric cancer patients. Furthermore, the GCSPC population expanded in primary gastric cancer cells under hypoxic condition in vitro, and hypoxic GCSPCs showed enhanced self-renewal ability, but reduced differentiation capacity, mediated by HIF-1alpha. In an animal model, GCSPCs preferentially resided in the hypoxic zone of PMSs; moreover, when the hypoxic microenvironment in PMSs was destroyed, GCPD was significantly alleviated. In conclusion, our results demonstrated that PMSs served as a hypoxic niche and favored GCSPCs peritoneal dissemination through HIF 1alpha both in vitro and in vivo. These results provided new insights into the GCPD process and may lead to advancements in the clinical treatment of gastric cancer. PMID- 25142306 TI - Natural large-scale regeneration of rib cartilage in a mouse model. AB - The clinical need for methods to repair and regenerate large cartilage and bone lesions persists. One way to make new headway is to study skeletal regeneration when it occurs naturally. Cartilage repair is typically slow and incomplete. However, an exception to this observation can be found in the costal cartilages, where complete repair has been reported in humans but the cellular and molecular mechanisms have not yet been characterized. In this study, we establish a novel animal model for cartilage repair using the mouse rib costal cartilage. We then use this model to test the hypothesis that the perichondrium, the dense connective tissue that surrounds the cartilage, is a tissue essential for repair. Our results show that full replacement of the resected cartilage occurs quickly (within 1 to 2 months) and properly differentiates but that repair occurs only in the presence of the perichondrium. We then provide evidence that the rib perichondrium contains a special niche that houses chondrogenic progenitors that possess qualities particularly suited for mediating repair. Label-retaining cells can be found within the perichondrium that can give rise to new chondrocytes. Furthermore, the perichondrium proliferates and thickens during the healing period and when ectopically placed can generate new cartilage. In conclusion, we have successfully established a model for hyaline cartilage repair in the mouse rib, which should be useful for gaining a more detailed understanding of cartilage regeneration and ultimately for developing methods to improve cartilage and bone repair in other parts of the skeleton. PMID- 25142307 TI - The use of a well-defined surface organometallic complex as a probe molecule: [(=SiO)Ta(V)Cl2Me2] shows different isolated silanol sites on the silica surface. AB - Ta(V)Cl2Me3 reacts with silica(700) and produces two different [(=SiO)Ta(V)Cl2Me2] surface organometallic species, suggesting a heterogeneity of the highly dehydroxylated silica surface, which was studied with a combined experimental and theoretical approach. PMID- 25142305 TI - The effects of vitamin C supplementation on pre-eclampsia in Mulago Hospital, Kampala, Uganda: a randomized placebo controlled clinical trial. AB - BACKGROUND: Oxidative stress plays a role in the pathogenesis of pre-eclampsia. Supplementing women with antioxidants during pregnancy may reduce oxidative stress and thereby prevent or delay the onset pre-eclampsia. The objective of this study was to evaluate the effect of supplementing vitamin C in pregnancy on the incidence of pre-eclampsia, at Mulago hospital, Kampala, Uganda. METHODS: This was a (parallel, balanced randomization, 1:1) placebo randomized controlled trial conducted at Mulago hospital, Department of Obstetrics and Gynecology. Participants included in this study were pregnant women aged 15-42 years, who lived 15 km or less from the hospital with gestational ages between 12-22 weeks. The women were randomized to take 1000mg of vitamin C (as ascorbic acid) or a placebo daily until they delivered. The primary outcome was pre-eclamsia. Secondary outcomes were: severe pre-eclampsia, gestational hypertension, preterm delivery, low birth weight and still birth delivery. Participants were 932 pregnant women randomized into one of the two treatment arms in a ratio of 1:1. The participants, the care providers and those assessing the outcomes were blinded to the study allocation. RESULTS: Of the 932 women recruited; 466 were randomized to the vitamin and 466 to the placebo group. Recruitment of participants was from November 2011 to June 2012 and follow up was up to January 2013. Outcome data was available 415 women in the vitamin group and 418 women in the placebo group.There were no differences in vitamin and placebo groups in the incidence of pre-eclampsia (3.1% versus 4.1%; RR 0.77; 95% CI: 0.37-1.56), severe pre-eclampsia (1.2% versus 1.0%; RR 1.25; 95% CI: 0.34-4.65), gestational hypertension(7.7% versus 11.5%; RR 0.67; 95% CI: 0.43-1.03), preterm delivery (11.3% versus 12.2%; RR 0.92; 95% CI: 0.63-1.34), low birth weight (11.1% versus 10.3%; RR 1.07; 95% CI: 0.72-1.59) and still birth delivery (4.6% versus 4.5%; RR 1.01; 95% CI: 0.54-1.87). CONCLUSIONS: Supplementation with vitamin C did not reduce the incidence of pre-eclampsia nor did it reduce the adverse maternal or neonatal outcomes. We do not recommend the use of vitamin C in pregnancy to prevent pre-eclampsia. TRIAL REGISTRATION: This study was registered at the Pan African Clinical Trial Registry, PACTR201210000418271 on 25th October 2012. PMID- 25142308 TI - Healthcare utilization in general practice before and after psychological treatment: a follow-up data linkage study in primary care. AB - OBJECTIVE: Literature suggests that serious mental health problems increase the use of health services and psychological interventions can reduce this effect. This study investigates whether this effect is also found in primary care patients with less serious mental health problems. DESIGN/SETTING: Routine electronic health records (EHR) from a representative sample of 128 general practices were linked to patient files from 150 primary care psychologists participating in the NIVEL Primary Care Database, using a trusted third party. Data were linked using the date of birth, gender, and postcode. This yielded 503 unique data pairs that were listed in one of the participating GP practices in 2008-2010, for people who had psychological treatment from a psychologist that ended in 2009. MAIN OUTCOME MEASURES: The number of contacts, health problems presented, and prescribed medication in general practice were analysed before and after the psychological treatment. RESULTS: Nearly all 503 patients consulted their GP during the six months preceding the psychological treatment (90.9%) and also in the six months after this treatment had ended (83.7%). The frequency of contacts was significantly higher before than after the psychological treatment (6.1 vs. 4.8). Fewer patients contacted their GPs specifically for psychological or social problems (46.3% vs. 38.8%) and fewer patients had anxiolytic drug prescriptions (15.5% vs. 7.6%) after psychological treatment. CONCLUSION: After psychological treatment, patients contact their GPs less often and present fewer psychological or social problems. Although contact rates seem to decrease, clients of psychologists are still frequent GP attenders. PMID- 25142309 TI - Emerging trends in hepatocellular carcinoma incidence and mortality. AB - The rise in incidence of hepatocellular carcinoma (HCC) in the United States has been well documented. The purpose of this analysis was to examine temporal trends in HCC incidence, mortality, and survival within the U.S. population. The Surveillance, Epidemiology, and End Results data were used to examine incidence and incidence-based (IB) mortality in HCC from 1973 to 2011. Secular trends in age-adjusted incidence and IB mortality by sex and cancer stage were characterized using the Joinpoint Regression program. In 1973, HCC incidence was 1.51 cases per 100,000, whereas in 2011, HCC incidence was 6.20 cases per 100,000. Although HCC incidence continues to increase, a slowing of the rate of increase occurs around 2006. In a sensitivity analysis, there was no significant increase in incidence and IB mortality from 2009 to 2011. There was a significant increase in overall median survival from the 1970s to 2000s (2 vs. 8 months; P < 0.001). On multivariable Cox's regression analysis, age, sex, race, tumor grade, stage at diagnosis, lymph/vascular invasion, number of primary tumors, tumor size, and liver transplant were independently associated with mortality. CONCLUSION: Our results indicate a deceleration in the incidence of HCC around 2006. Since 2009 and for the first time in four decades, there is no increase in IB mortality and incidence rates for HCC in the U.S. population. The nonsignificant increase in incidence and IB mortality in recent years suggest that the peak of the HCC epidemic may be near. A significant survival improvement in HCC was also noted from 1973 to 2010, which seems to be driven by earlier detection of HCC at a curative stage and greater utilization of curative modalities (especially transplant). PMID- 25142310 TI - Label-free sensitive electrogenerated chemiluminescence aptasensing based on chitosan/Ru(bpy)32+/silica nanoparticles modified electrode. AB - In this work, a label-free and sensitive electrogenerated chemiluminescence (ECL) aptasensing scheme for K(+) was developed based on G-rich DNA aptamer and chitosan/Ru(bpy)3(2+)/silica (CRuS) nanoparticles (NPs)-modified glass carbon electrode. This ECL aptasensing approach has benefited from the observation that the G-rich DNA aptamer at the unfolded state showed more ECL enhancing signal at CRuS NPs-modified electrode than the binding state with K(+), which folds into G quadruplex structure. As such, the decreasing ECL signals could be used to detect K(+). Compared to other aptasensing K(+) approaches previously reported, the proposed ECL sensing scheme is a label-free aptasensing strategy, which eliminates the labeling, separation, and immobilization steps, and behaves in a simple, low-cost way. More importantly, because the proposed ECL sensing mechanism utilizes the nanosized ECL active CRuS NPs to sense the nanoscale conformation change from the aptamer binding to target, it is specific. In addition, due to the great conformation changes of the aptamer's G-bases on CRuS NPs and the excellent ECL enhancing effect of guanine bases to the Ru(bpy)3(2+) ECL reaction, a 0.3 nM detection limit for K(+) was achieved with the proposed ECL method. On the basis of these advantages, the proposed ECL aptasensing method was also successfully used to detect K(+) in colorectal cancer cells. PMID- 25142311 TI - The utility of routine polyp histopathology after endoscopic sinus surgery. AB - BACKGROUND: Routine histopathological assessment is standard practice for nasal polyp specimens obtained during endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Retrospective studies suggest that routine histopathology of nasal polyps shows few unexpected diagnoses that alter patient management. Our objective was to study the use of routine pathological analysis, and its cost to the healthcare system, in a prospective manner. METHODS: A multicenter prospective assessment was performed from data collected between 2007 and 2013. Only cases of patients undergoing ESS for bilateral CRS were included. We excluded unilateral disease cases, and cases in which diagnoses other than polyps were suspected either preoperatively or intraoperatively. We then compared the preoperative diagnosis with the final histopathology and identified the rate of unexpected pathologies. A cost analysis was performed. RESULTS: Only 4 of 866 pathological specimens were identified as having a clinically significant unexpected diagnosis. All unexpected pathologies in this series were benign. These 4 cases account for 0.46% of all specimens reviewed. This translates to a number needed to screen of 217 cases of bilateral CRS to discover 1 unexpected pathology. The associated cost for making an unexpected diagnosis was $19,192.73. CONCLUSION: Routine histopathology of nasal polyps in ESS for bilateral CRS with polyps yields few unexpected and management-altering diagnoses. It carries a significant cost to the healthcare system. In cases of bilateral CRS with no other concerning clinical features, clinicians should exercise judgment in submitting polyp specimens for pathology rather than routinely sending polyps for histopathologic analysis. PMID- 25142312 TI - Ethanolic extract of Ferula gummosa is cytotoxic against cancer cells by inducing apoptosis and cell cycle arrest. AB - Ferula gummosa Boiss. has medicinal applications in treating a wide range of diseases including cancer. The objective of this study was to evaluate the antiproliferative activities of the seed and gum extracts of F. gummosa as well as to study the effect of the potent extract on the induction of apoptosis and cell cycle arrest. Our results demonstrated that the ethanolic extract had the lowest IC50 value at 72 h (0.001 +/- 1.2 mg/mL) in BHY cells. Moreover, flowcytometry and annexin-V analysis revealed that the ethanolic extract induced apoptosis and cell-cycle arrest in BHY cells at G1/S phase. In addition, colorimetric methods exhibited the highest amount of total phenolics and flavonoids in the aqueous and gum extracts (0.12 +/- 0.037, 0.01 +/- 2.51 mg/g of dry powder). Generally, the results obtained indicate that F. gummosa ethanol extract may contain effective compounds which can be used as a chemotherapeutic agent. PMID- 25142313 TI - Therapeutic uses of anti-interleukin-6 receptor antibody. AB - Cytokine-targeted therapy has generated a paradigm shift in the treatment of several immune-mediated diseases. Interleukin-6 (IL-6), which was initially identified as B-cell stimulatory factor 2, is a prototypical cytokine with wide ranging biological effects on immune cells such as B and T cells, on hepatocytes, hematopoietic cells, vascular endothelial cells and on many others. IL-6 is thus crucially involved in the regulation of immune responses, hematopoiesis and inflammation. When infections and tissue injuries occur, IL-6 is promptly synthesized and performs a protective role in host defense against such stresses and traumas. However, excessive production of IL-6 during this emergent process induces potentially fatal complications, including systemic inflammatory response syndrome (SIRS), and dysregulated, persistently high expression of IL-6 causes the onset or development of various chronic immune-mediated disorders. For these reasons, IL-6 blockade was expected to become a novel therapeutic strategy for various diseases characterized by IL-6 overproduction. Indeed, worldwide clinical trials of tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody, have successfully proved its outstanding efficacy against rheumatoid arthritis, juvenile idiopathic arthritis and Castleman disease, leading to the approval of tocilizumab for the treatment of these diseases. Moreover, various reports regarding off-label use of tocilizumab strongly suggest that it will be widely applicable for acute, severe complications such as SIRS and cytokine-release syndrome and other refractory chronic immune-mediated diseases. PMID- 25142314 TI - Micropatterning electrospun scaffolds to create intrinsic vascular networks. AB - Sufficient vascularization is critical to sustaining viable tissue-engineered (TE) constructs after implantation. Despite significant progress, current approaches lack suturability, porosity, and biodegradability, which hinders rapid perfusion and remodeling in vivo. Consequently, TE vascular networks capable of direct anastomosis to host vasculature and immediate perfusion upon implantation still remain elusive. Here, a hybrid fabrication method is presented for micropatterning fibrous scaffolds that are suturable, porous, and biodegradable. Fused deposition modeling offers an inexpensive and automated approach to creating sacrificial templates with vascular-like branching. By electrospinning around these poly(vinyl alcohol) templates and dissolving them in water, microvascular patterns were transferred to fibrous scaffolds. Results indicated that these scaffolds have sufficient suture retention strength to permit direct anastomosis in future studies. Vascularization of these scaffolds is demonstrated by in vitro endothelialization and perfusion. PMID- 25142315 TI - Overview of the organization of protease genes in the genome of Leishmania spp. AB - BACKGROUND: The genus Leishmania includes protozoan parasites that are able to infect an array of phlebotomine and vertebrate species. Proteases are related to the capacity of these parasites to infect and survive in their hosts and are therefore classified as virulence factors. FINDINGS: By analyzing protease genes annotated in the genomes of four Leishmania spp [Leishmania (Leishmania) infantum, L. (L.) major, L. (L.) mexicana and L. (Viannia) braziliensis], these genes were found on every chromosome of these protozoa. Four protease classes were studied: metallo-, serine, cysteine and aspartic proteases. Metalloprotease genes predominate in the L. (V.) braziliensis genome, while in the other three species studied, cysteine protease genes prevail. Notably, cysteine and serine protease genes were found to be very abundant, as they were found on all chromosomes of the four studied species. In contrast, only three aspartic protease genes could be detected in these four species. Regarding gene conservation, a higher number of conserved alleles was observed for cysteine proteases (42 alleles), followed by metalloproteases (35 alleles) and serine proteases (15 alleles). CONCLUSIONS: The present study highlights substantial differences in the organization of protease genes among L. (L.) infantum, L. (L.) major, L. (L.) mexicana and L. (V.) braziliensis. We observed significant distinctions in many protease features, such as occurrence, quantity and conservation. These data indicate a great diversity of protease genes among Leishmania species, an aspect that may be related to their adaptations to the peculiarities of each microenvironment they inhabit, such as the gut of phlebotomines and the immune cells of vertebrate hosts. PMID- 25142316 TI - [Correct performance of transfusion]. AB - The administration of blood products is strictly regulated. Warming of blood components at body temperature is required only in rare cases. Addition of drugs to blood products is not allowed. During transfusion the monitoring of the patient is continued. In the case of an adverse event, exclusion of acute hemolysis is very important. As emergency transfusions have a higher risk than standard transfusions, their indications have to be restricted. When transfusion is completed the blood bag has to be preserved for 24 h. The effects of the blood transfusion have to be controlled. The administration of blood products must be documented to allow a possible cross-check from the recipient to the donor as well as from the donor to the recipient. The disposal of administered and of non administered blood components is subject to the guidelines for hospital waste. PMID- 25142317 TI - [Comments on: erythropoietin administration and transfusion regimen after traumatic brain injury]. PMID- 25142318 TI - p42.3: An abductor of cell cycle. AB - As a newly discovered tumor-associated gene, p42.3 was originally ascertained in gastric cancer cell line BGC823 and has been confirmed as a cell cycle-dependent gene that is overexpressed in many human tumor cell lines and embryonic tissues. p42.3 can regulate the level of relevant cycle-dependent proteins and promote malignant transformation of cells. A variety of cellular functions, including cell proliferation, cell invasion and cell migration, are under control of p42.3. Our review, namely the introduction of the structure of p42.3, underlying activity regulation mechanisms of p42.3 as well as the role p42.3 plays in malignant cellular transformation process, are accompanied by the presentation of potential directions of further researches of cancer prevention and therapy in which p42.3 is inevitable. PMID- 25142319 TI - Potential anticancer agents. I. Synthesis of isoxazole moiety containing quinazoline derivatives and preliminarily in vitro anticancer activity. AB - 14 new structures of isoxazole-moiety-containing quinazoline derivatives(3a~3n) were synthesized for the first time and characterized by IR, (1)H NMR, (13)C NMR, ESI-MS. Subsequently, their in vitro anticancer activity against A549, HCT116 and MCF-7 cell lines was preliminarily evaluated using the MTT method. Among them, most compounds showed good to excellent anticancer activity, especially 3d, 3i, 3k and 3m exhibited the more potent anticancer activity against A549, HCT116 and MCF-7 cell lines, which can be regarded as the promising drug candidates for development of anticancer drugs. PMID- 25142322 TI - Alprolix (recombinant Factor IX Fc fusion protein): extended half-life product for the prophylaxis and treatment of hemophilia B. AB - Hemophilia B is a genetic disease caused by mutation of the gene for coagulation protein Factor IX. When severe, the disease leads to spontaneous life-threatening bleeding episodes. Current therapy requires frequent intravenous infusions of therapeutic recombinant or plasma-derived protein concentrates containing Factor IX. AlprolixTM (recombinant Factor IX Fc fusion protein), is a therapeutic Factor IX preparation that has been engineered for a prolonged half-life in circulation, has completed pivotal clinical trials and has been approved recently in the USA, Canada, Australia and Japan for use in the clinic for patients with hemophilia B. This promising therapy should allow patients to use fewer infusions to maintain appropriate Factor IX activity levels in all clinical settings, and its use may be indicated in both on demand and prophylactic treatments. PMID- 25142320 TI - Serum levels of retinol-binding protein-4 are associated with the presence and severity of coronary artery disease. AB - BACKGROUND: The interplay between the novel adipokine retinol-binding protein-4 (RBP4) and coronary artery disease (CAD) is still obscure. We investigated the relationship between RBP4 levels and the presence and severity of angiographically proven CAD and determined its possible role in acute myocardial infarction (AMI). METHODS: 305 individuals with angiographically proven CAD (CAD patients), were classified into 2 subgroups: 1) acute myocardial infarction (AMI, n = 141), and 2) stable angina (SA, n = 164). Ninety-one age- and sex-matched individuals without CAD, but with at least 2 classical cardiovascular risk factors, served as controls (non-CAD group). RBP4 serum levels were measured at hospital admission and were analyzed in relation to the coronary severity stenosis, assessed by the Gensini-score and the number of coronary narrowed vessels. Other clinical parameters, including insulin levels, HOMA-IR, hsCRP, glycaemic and lipid profile, and left-ventricular ejection fraction were also assessed. RESULTS: Serum RBP4 levels were significantly elevated in patients with CAD compared to non-CAD patients (39.29 +/- 11.72 mg/L vs. 24.83 +/- 11.27 mg/L, p < 0.001). We did not observe a significant difference in RBP4 levels between AMI and SA subgroups (p = 0.734). Logistic regression analysis revealed an independent association of CAD presence with serum RBP4 (beta = 0.163, p = 0.006), and hsCRP (beta = 0.122, p = 0.022) levels, in the whole study group. Among variables, hsCRP (beta = 0.220), HDL (beta = -0.150), and RBP4 (beta = 0.297), correlated in both univariate and multivariate analysis with CAD severity (R2 = 0.422, p < 0.001). Similarly, RBP4 concentrations increased with the number of coronary narrowed vessels (p < 0.05). CONCLUSION: Patients with CAD, both SA and AMI, showed elevated RBP4 serum levels. Notably, increased RBP4 concentration seemed to independently correlate with CAD severity, but no with AMI. TRIAL REGISTRATION: The ClinicalTrials.gov Identifier is: NCT00636766. PMID- 25142321 TI - The role of substance use and morality in violent crime - a qualitative study among imprisoned individuals in opioid maintenance treatment. AB - BACKGROUND: Opioid maintenance treatment (OMT) is regarded as a crime control measure. Yet, some individuals are charged with violent criminal offenses while enrolled in OMT. This article aims to generate nuanced knowledge about violent crime among a group of imprisoned, OMT-enrolled individuals by exploring their understandings of the role of substances in violent crime prior to and during OMT, moral values related to violent crime, and post-crime processing of their moral transgressions. METHODS: Twenty-eight semi-structured interviews were undertaken among 12 OMT-enrolled prisoners. The interviews were audio recorded and transcribed verbatim. An exploratory, thematic analysis was carried out with a reflexive and interactive approach. FINDINGS: Prior to OMT, substances and, in particular, high-dose benzodiazepines were deliberately used to induce 'antisocial selves' capable of transgressing individual moral codes and performing non-violent and violent criminal acts, mainly to support costly heroin use. During OMT, impulsive and uncontrolled substance use just prior to the violent acts that the participants were imprisoned for was reported. Yet, to conduct a (violent) criminal act does not necessarily imply that one is without moral principles. The study participants maintain moral standards, engage in complex moral negotiations, and struggle to reconcile their moral transgressions. Benzodiazepines were also used to reduce memories of and alleviate the guilt associated with having committed violent crimes. CONCLUSIONS: Substances are used to transgress moral codes prior to committing and to neutralize the shame and guilt experienced after having committed violent crimes. Being simultaneously enrolled in OMT and imprisoned for a (violent) crime might evoke feelings of 'double' shame and guilt for both the criminal behavior prior to treatment and the actual case(s) one is imprisoned for while in OMT. Treatment providers should identify individuals with histories of violent behavior and, together with them, explore concrete episodes of violence and their emotional reactions. Particular attention should be given to potential relationships between substance use and violence and treatment approaches tailored accordingly. What appears as severe antisocial personality disorder may be partly explained by substance use. PMID- 25142323 TI - Prediction of brain clozapine and norclozapine concentrations in humans from a scaled pharmacokinetic model for rat brain and plasma pharmacokinetics. AB - BACKGROUND: Clozapine is highly effective in treatment-resistant schizophrenia, although, there remains significant variability in the response to this drug. To better understand this variability, the objective of this study was to predict brain extracellular fluid (ECF) concentrations and receptor occupancy of clozapine and norclozapine in human central nervous system by translating plasma and brain ECF pharmacokinetic (PK) relationships in the rat and coupling these with known human disposition of clozapine in the plasma. METHODS: Unbound concentrations of clozapine and norclozapine were measured in rat brain ECF using quantitative microdialysis after subcutaneous administration of a 10 mg/kg single dose of clozapine or norclozapine. These data were linked with plasma concentrations obtained in the same rats to develop a plasma-brain ECF compartmental model. Parameters describing brain ECF disposition were then allometrically scaled and linked with published human plasma PK to predict human ECF concentrations. Subsequently, prediction of human receptor occupancy at several CNS receptors was based on an effect model that related the predicted ECF concentrations to published concentration-driven receptor occupancy parameters. RESULTS: A one compartment model with first order absorption and elimination best described clozapine and norclozapine plasma concentrations in rats. A delay in the transfer of clozapine and norclozapine from plasma to the brain ECF compartment was captured using a transit compartment model approach. Human clozapine and norclozapine concentrations in brain ECF were simulated, and from these the median percentage of receptor occupancy of dopamine-2, serotonin-2A, muscarinic-1, alpha-1 adrenergic, alpha-2 adrenergic and histamine-1 for clozapine, and dopamine-2 for norclozapine were consistent with values reported in the literature. CONCLUSIONS: A PK model that relates clozapine and norclozapine disposition in rat plasma and brain, including blood-brain barrier transport, was developed. Using allometry and published human plasma PK, the model was successfully translated to predict clozapine and norclozapine concentrations and accordant receptor occupancy of both agents in human brain. These predicted exposure and occupancy measures at several receptors that bind clozapine may be employed to extend our understanding of clozapine's complex behavioral effects in humans. PMID- 25142324 TI - Collision-induced dissociation of fatty acid [M - 2H + Na]- ions: charge-directed fragmentation and assignment of double bond position. AB - The collision-induced dissociation (CID) of cationic fatty acid-metal ion complexes has been extensively studied and, in general, provides rich structural information. In particular, charge-remote fragmentation processes are commonly observed allowing the assignment of double bond position. In a previous manuscript, we presented two methods to doubly deprotonate polyunsaturated fatty acids to form anionic fatty acid-sodium ion complexes, referred to as [M - 2H + Na] (-) ions. In the current manuscript, the CID behavior of these [M - 2H + Na] (-) ions is investigated for the first time. Significantly, we also present a deuterium-labeling experiment, which excludes the possibility that deprotonation occurs predominately at the alpha-carbon in the formation of fatty acid [M - H + NaF](-) ions. This supports our original proposal where deprotonation occurs at the bis-allylic positions of polyunsaturated fatty acids. CID spectra of polyunsaturated fatty acid [M - 2H + Na](-) ions display abundant product ions arising from acyl chain cleavages. Through the examination of fatty acid isomers, it is demonstrated that double bond position may be unequivocally determined for methylene-interrupted polyunsaturated fatty acids with three or more carbon carbon double bonds. In addition, CID of [M - 2H + Na](-) ions was applied to 18:3 isomers of Nannochloropsis oculata and three isomers were tentatively identified: ?(9,12,15)18:3, ?(6,9,12)18:3, and ?(5,8,11)18:3. We propose that structurally-informative product ions are formed via charge-driven fragmentation processes at the site of the resonance-stabilized carbanion as opposed to charge remote fragmentation processes, which could be inferred if deprotonation occurred predominately at the alpha-carbon.